PMID- 24274507
TI  - Purification of a fucoidan from kelp polysaccharide and its inhibitory kinetics
      for tyrosinase.
AB  - High-speed countercurrent chromatography (HSCCC) was used to separate kelp
      polysaccharide. HSCCC was performed using an aqueous two-phase solvent system
      composed of PEG1000-K2HPO4-KH2PO4-H2O (0.5:1.25:1.25:7.0, w/w) by eluting a lower
      aqueous phase at 2.0 mL/min at 600 rpm, yielding two separate fractions, KPS-1
      and KPS-2. The KPS-2 fraction was further purified by DEAE-Sepharose fast flow
      anion-exchange column chromatography to provide 3 fractions, KPS-2-1, KPS-2-2 and
      KPS-2-3. GPC-HPLC analysis indicated that KPS-2-1 fraction was a purified
      fucoidan. FT-IR analysis showed that KPS-2-1 was a sulphated polysaccharide. An
      analysis of enzymatic kinetics showed that the purified fucoidan was a
      competitive inhibitor of tyrosinase toward l-tyrosine, and the inhibitory
      constant Ki obtained from double-reciprocal plots was 0.9907 mg/mL.

PMID- 24274508
TI  - Guar gum-g-N,N'-dimethylacrylamide: synthesis, characterization and applications.
AB  - The graft copolymerization of N,N'-dimethylacrylamide onto guar gum initiated by
      potassium peroxymonosulphate/glycolic acid redox pair in an aqueous medium was
      studied gravimetrically under a nitrogen atmosphere. Grafting ratio, grafting
      efficiency and add on increase on increasing the concentration of potassium
      peroxymonosulphate (8.0 * 10(-3) to 24.0 * 10(-3) mol dm(-3)) and glycolic acid
      concentration (4.4 * 10(-3) to 7.6 * 10(-3) mol dm(-3)). On increasing the
      hydrogen ion concentration from 4 * 10(-3) to 12.0 * 10(-3) mol dm(-3), grafting
      ratio, efficiency, add on and conversion were increased. Maximum grafting was
      obtained when guar gum and N,N'-dimethylacrylamide concentration were 1.0 * 10(
      2) g dm(-3) and 14.0 * 10(-2) mol dm(-3), respectively. An increase in
      temperature from 25  degrees C to 45  degrees C, the grafting ratio increases but
      conversion and homopolymer decrease. The optimum time period for graft
      copolymerization was 2h. The graft copolymers were characterized by IR
      spectroscopy and thermogravimetric analysis.

PMID- 24274509
TI  - Studies on Tinospora cordifolia monosugars and correlation analysis of uronic
      acids by spectrophotometric methods and GLC.
AB  - Cold water-soluble (CWSP) and hot water soluble polysaccharides (HWSP) from
      Tinospora cordifolia stems were isolated and purified in 2.99% and 1.99% yield
      respectively. Complete hydrolysis followed by paper chromatography and GLC
      analysis indicated the presence of L-rhamnose, L-arabinose, D-xylose, D-mannose,
      D-galactose and D-glucose in molar ratio of 0.857, 1.106, 0.727, 0.526, 0.708 and
      95.763 in CWSP and 0.697, 0.777, 2.048, 0.777, 0.292 and 95.408 in HWSP. The
      uronic acid content in the polysaccharide has been studied extensively using
      assorted approaches. It was quantitatively estimated by GLC analysis and
      spectrophotometric methods using carbazole, m-hydroxydiphenyl and 3,5
      dimethylphenol as colorimetric reagents. GLC analyses indicated galacturonic acid
      content of 3.06% and 5.16% in CWSP and HWSP respectively. Estimation of uronic
      acid using 3,5-dimethylphenol corroborated the above analysis. The study resulted
      in composition of constituent monosugars of CWSP and HWSP and co-relation
      analysis of uronic acid content, leading to an unambiguous structural analysis.

PMID- 24274510
TI  - Chitosan and cyclodextrin in intranasal microemulsion for improved brain
      buspirone hydrochloride pharmacokinetics in rats.
AB  - The aim of this study was to develop buspirone hydrochloride microemulsion
      formulations for intranasal administration to improve the drug bioavailability
      and provide high drug brain levels. For the purpose, chitosan aspartate, and
      hydroxypropyl-beta-cyclodextrin were incorporated in the microemulsions. The
      prepared formulations were characterized. Biological investigations including
      pharmacokinetic studies, brain drug targeting efficiency determinations and
      histopathological examinations were performed on rats. The results showed that
      safe and stable mucoadhesive microemulsion suitable for nasal administration were
      successfully prepared. Ex vivo drug permeation revealed high drug permeation from
      microemulsions. Absolute bioavailability after intranasal administration of
      buspirone mucoadhesive microemulsion increased significantly and plasma
      concentration peaked at 15 min. The AUC0-360(brain) was 3 times that obtained
      after intravenous administration. A high brain targeting efficiency (86.6%) and a
      direct nose to brain transport (88%) confirmed the direct nose to brain transport
      of buspirone following nasal administration of the microemulsions.

PMID- 24274511
TI  - Dispersion of SiC nanoparticles in cellulose for study of tensile, thermal and
      oxygen barrier properties.
AB  - Cellulose/silicon carbide (cellulose/SiC) nanobiocomposites were prepared by
      solution technique. The interaction of SiC nanoparticles with cellulose were
      confirmed by Fourier transformed infrared (FTIR) spectroscopy. The structure of
      cellulose/SiC nanobiocomposites was investigated by X-ray diffraction (XRD), and
      transmission electron microscopy (TEM). The tensile properties of the
      nanobiocomposites were improved as compared with virgin cellulose. Thermal
      stabilities of cellulose/SiC nanobiocomposites were studied by thermogravimetric
      analysis (TGA). The cellulose/SiC nanobiocomposites were thermally more stable
      than the raw cellulose. It may be due to the delamination of SiC with cellulose
      matrix. The oxygen barrier properties of cellulose composites were measured using
      gas permeameter. A substantial reduction in oxygen permeability was obtained with
      increase in silicon carbide concentrations. The thermally resistant and oxygen
      barrier properties of the prepared nanobiocomposites may enable the materials for
      the packaging applications. 

PMID- 24274512
TI  - Effects of bagasse microfibrillated cellulose and cationic polyacrylamide on key
      properties of bagasse paper.
AB  - This study explores the benefits of using bagasse microfibrillated cellulose
      (MFC) in bagasse paper. Two different types of MFC were produced from DED
      bleached soda bagasse pulp. The MFC was added to soda bagasse pulp furnishes in
      different amounts. Cationic polyacrylamide (C-PAM) was selected as retention aid.
      The results show that addition of MFC increased the strength of paper as
      expected. Interestingly, 1% MFC in combination with 0.1% C-PAM yielded similar
      drainage time as the reference pulp, which did not contain MFC. In addition, the
      samples containing 1% MFC and 0.1% C-PAM yielded (i) a significant increment of
      the tensile index, (ii) a minor decrease of opacity and (iii) preserved Gurley
      porosity. Hence, this study proves that small fractions of MFC in combination
      with adequate retention aids can have positive effects with respect to paper
      properties, which is most interesting from an industrial point of view. 

PMID- 24274513
TI  - Extraction, purification and characterization of polysaccharides from Hawk tea.
AB  - In the present study, the extraction, purification and characterization of
      polysaccharides from Hawk mature leaf tea (HMP) were investigated. The optimal
      extraction parameters were obtained by using a Box-Behnken design as follows:
      extraction temperature 88.9  degrees C, extraction time 128.2 min and ratio of
      water to solid 11.4 mL/g. The crude HMP was sequentially purified by
      chromatography of DEAE-52, and two purified fractions, HMP-1 and HMP-2, were
      obtained. HMP-1 and HMP-2 were mainly composed of arabinose, galactose, glucose
      and mannose with the molecular weight of 133 and 100 kDa, respectively. For
      antioxidant activities in vitro, HMP-1 had strong 2,2-diphenyl-1-picryl-hydrazyl
      (DPPH) radical scavenging activity and ferric reducing activity power (FRAP).
      These results provide a scientific basis for the further use of polysaccharides
      from this traditional herb tea.

PMID- 24274514
TI  - Modeling of starch retrogradation onset in its aqueous solution using
      thermoreversible gelation concept.
AB  - A model was developed to predict starch retrogradation onset in its aqueous
      solution and verified with the selected literature data. The most probable chain
      helix distribution was first estimated via minimizing the system free energy with
      respect to chain helix length. Later, the calculation was extended to double
      helix formation among single polymer chains with zeta2=10 as the retrogradation
      criterion. zeta2 is the average double helix length usually equals 10 implying
      the number of participating residues in the thickness of the thinnest reported
      starch lamella in the literature. The model prediction namely the retrogradation
      onset temperature, showed quite reasonable agreement with the selected literature
      data. Equal chain conformational entropy loss, Deltas/k(B)~-0.7, was inferred for
      various starch aqueous solutions due to the double helix kind of associations.
      Nonetheless, the studied systems showed distinct restrictions, sigma=9 * 10(-4)
      4.7 * 10(-3), against association.

PMID- 24274515
TI  - Structural analysis and characterization of dextran produced by wild and mutant
      strains of Leuconostoc mesenteroides.
AB  - An exopolysaccharide known as dextran was produced by Leuconostoc mesenteroides
      KIBGE-IB22 (wild) and L. mesenteroides KIBGE-IB22M20 (mutant). The structure was
      characterized using FTIR, (1)H NMR, (13)C NMR and 2D NMR spectroscopic
      techniques, whereas surface morphology was analyzed using SEM. A clear difference
      in the spectral chemical shift patterns was observed in both samples. All the
      spectral data indicated that the exopolysaccharide produced by KIBGE-IB22 is a
      mixture of two biopolymers. One was dextran in alpha-(1 -> 6) configuration with
      a small proportion of alpha-(1 -> 3) branching and the other was levan containing
      beta-(2 -> 6) fructan fructofuranosyl linkages. However, remarkably the mutant
      only produced dextran without any concomitant production of levan. Study
      suggested that the property of KIBGE-IB22M20, regarding improved production of
      high molecular weight dextran in a shorter period of fermentation time without
      any contamination of other exopolysaccharide, could be employed to make the
      downstream process more feasible and cost effective on large scale.

PMID- 24274516
TI  - Mapping of low molecular weight heparins using reversed phase ion pair liquid
      chromatography-mass spectrometry.
AB  - Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated
      and negatively charged, linear carbohydrate polymers prepared by chemical or
      enzymatic depolymerization of heparin. They are widely used as anticoagulant
      drugs possessing better bioavailability, longer half-life, and lower side effects
      than heparin. Comprehensive structure characterization of LMWHs is important for
      drug quality assurance, generic drug application, and new drug research and
      development. However, fully characterization of all oligosaccharide chains in
      LMWHs is not feasible for current available analytical technologies due to their
      structure complexity and heterogeneity. Fingerprinting profiling is an efficient
      way for LMWHs' characterization and comparison. In this work, we present a
      simple, sensitive, and powerful analytical approach for structural
      characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were
      analyzed using reversed phase ion pair electrospray ionization mass spectrometry
      (RPIP-ESI-MS). More than 200 components were identified, including major
      structures, minor structures, and process related impurities. This approach is
      robust for high resolution and complementary fingerprinting analysis of LMWHs. 

PMID- 24274517
TI  - Starch/carrageenan/milk proteins interactions studied using multiple staining and
      Confocal Laser Scanning Microscopy.
AB  - This study focused on the effects of the interactions between modified waxy maize
      starch, kappa carrageenan and skim milk on the microstructure of their mixed
      systems using Confocal Laser Scanning Microscopy (CLSM). A multiple staining of
      the components was set up with a view to improving starch covalent staining. In
      starch/carrageenan pasted mixtures, carrageenan was found to adsorb on and
      penetrate slightly into the starch granules, whereas no interactions were
      observed between starch and milk proteins. In ternary mixtures, interactions
      between starch granules and carrageenan were no longer observed, even when milk
      proteins were added after starch swelling in the carrageenan solution, thus
      showing preferential interactions between carrageenan/milk proteins in comparison
      to carrageenan/starch granules. Modifying the blending order of the components
      led to microstructure differences depending on several parameters such as
      starch/carrageenan interactions, carrageenan/milk proteins network structure,
      level of starch granules disruption and amylopectin contribution to the
      microstructure. 

PMID- 24274518
TI  - Quaternized and sulfated xylan derivative films.
AB  - Xylan quaternized sulfate films were prepared from beech xylan (X) and compared
      with fully sulfated xylan films (XS). When quaternized xylan (QX) was prepared in
      the first step (DS(Q)=0.55), than by sulfation of QX in the second step the fully
      substituted ampholytic derivative (QXS; DS(Q)=0.33; DS(S)=1.67) could be
      obtained. By sulfation in first step, xylan sulphate (SX, DS(S)=0.70) was
      obtained and by subsequent quaternization, SXQ film with DSQ=0.55 and DSS=0.33
      which contained partially unsubstituted hydroxyls. The molar masses (M(n)) of the
      film's soluble parts were increasing in order X<SX<SXQ<QX<XS<QXS. In all films
      there were some insoluble particles present as determined by the amount of
      recovered masses by SEC-MALS. The materials were further characterized by AFM,
      XRD, TG/DTG/DTA, NMR and mechanical testing. QXS and SXQ could form mechanically
      more stable films than XS specimens.

PMID- 24274519
TI  - In vitro and in vivo antioxidant activities of polysaccharide purified from aloe
      vera (Aloe barbadensis) gel.
AB  - The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from
      aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera
      gel by using ten digestive enzymes including five carbohydrases and five
      proteases. Among them, the highest yield was obtained with the Viscozyme extract
      and the same extract showed the best radical scavenging activity. An active
      polysaccharide was purified from the Viscozyme extract using ethanol-added
      separation and anion exchange chromatography. Purified aloe vera polysaccharide
      (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In
      addition, APS showed a protective effect against AAPH-induced oxidative stress
      and cell death in Vero cells as well as in the in vivo zebrafish model. In this
      study, it is proved that both the in vitro and in vivo antioxidant potentials of
      APS could be further utilized in relevant industrial applications. 

PMID- 24274520
TI  - A non-hemorrhagic hybrid heparin/heparan sulfate with anticoagulant potential.
AB  - The structural characterization and the anticoagulant potential of a novel
      heparin/heparan sulfate-like compound from the heads of Litopenaeus vannamei
      shrimp are described. While it is distinct from either heparin or heparan
      sulfate, enzymatic depolymerization and nuclear magnetic resonance spectroscopy
      analyses revealed that this molecule does share some structural features with
      heparin, such as the high degree of N- and 6-O-sulfation and minor N-acetylation,
      and with heparan sulfate, in the glucuronic acid content. Its ability to
      stabilize human antithrombin explains its significant anticoagulant activity in
      aPTT and Factor-Xa inhibition assays. Interestingly, in contrast to mammalian
      heparin, the shrimp compound displayed negligible hemorrhagic effect. Together,
      these findings have particular interest since they reveal a novel molecule with
      significant anti-Xa activity coupled with low bleeding effects which make the
      shrimp heparin/HS-like compound a potential alternative for mammalian heparin. 

PMID- 24274521
TI  - Enzymatic esterification of tapioca maltodextrin fatty acid ester.
AB  - In this work new types of hydrophobically modified maltodextrin were prepared by
      enzyme-catalyzed reaction of maltodextrin and three fatty acids: decanoic acid (C
      10), lauric acid (C-12) and palmitic acid (C-16). Lipase obtained from
      Thermomyces lanuginosus was found to be a useful biocatalyst in the maltodextrin
      esterification. Esterified maltodextrin with a degree of substitution (DS) 0.015
      0.084 was prepared at the optimum conditions of 60  degrees C for 4 h. The DS was
      found to be at its highest when maltodextrin and fatty acids were taken in the
      ratio 1:0.5. The functional properties of these esterified maltodextrin were
      investigated. All esterified maltodextrin did not completely dissolve in water.
      Esterified maltodextrin at a concentration of 25% (w/w) exhibited Newtonian flow
      behavior similar to that of native maltodextrin. Esterified maltodextrin had a
      higher viscosity compare to native maltodextrin. X-ray diffraction pattern of
      esterified maltodextrin indicated crystallization of the fatty acid side chains.
      The thermal stability of esterified maltodextrin was checked by differential
      scanning calorimetry (DSC). Esterified maltodextrin was then used as an
      emulsifier to make n-hexadecane O/W emulsions. The emulsions were characterized
      according to their oil droplet characteristics and emulsification index.

PMID- 24274522
TI  - Physicochemical properties of granular and non-granular cationic starches
      prepared under ultra high pressure.
AB  - Granular and non-granular cationic starches were prepared through the reaction of
      tapioca and corn starches with 2,3-epoxypropyl trimethyl ammonium chloride
      (ETMAC) using conventional and ultra high pressure (UHP)-assisted reactions. The
      cationic starches were characterized with respect to morphology, degree of
      substitution (DS), FT-IR, (13)C NMR, X-ray diffraction pattern, solubility and
      swelling power, pasting viscosity, and flocculating activity. Non-granular
      (relative to granular) cationic starches possessed higher DS values. While DS
      values of non-granular cationic starches were lower for UHP-assisted (relative to
      conventional) reaction, granular cationic starches did not differ for both
      reactions. For flocculation activity, granular cationic starches with lower
      solubility and higher swelling power were higher than non-granular counterparts
      with reversed patterns in solubility and swelling power, regardless of
      conventional and UHP-assisted reactions. Overall results suggested that
      flocculation activity of cationic starches may be directly associated with their
      swelling powers (relative to DS values). 

PMID- 24274523
TI  - The regulation of DNA adsorption and release through chitosan multilayers.
AB  - To sustain transgene expression, chitosan was studied to immobilize DNA using
      layer-by-layer assembly to form polyelectrolyte multilayers (PEMs). Higher DNA
      concentrations and longer deposition periods demonstrated more DNA adsorptions to
      PEMs. By adjusting pH and the molecular weight of chitosan, PEM structures were
      manipulated. Chitosan molecules adsorption to PEMs increased when they were at pH
      6 because of their low protonation. Furthermore, the configuration of chitosan
      favored a coiled-form when the pH was high, as the intramolecular repulsion
      decreased. Therefore, interdiffusion of polyelectrolytes in PEMs was promoted to
      increase DNA adsorption, especially for chitosan with high molecular weight. For
      the release experiments, because PEMs fabricated by lower pH chitosan owned less
      chitosan molecules, DNA release was enhanced. However, this phenomenon did not
      happen to chitosan with high molecular weight, which should be due to the
      entanglement between polymer chains. This comprehensive approach should be
      beneficial to substrate-mediated gene delivery applications. 

PMID- 24274524
TI  - Synthesis and cardio protective biological applications of glucodendrimers by
      H9C2 cell studies.
AB  - Novel glucodendrimers scaffolds containing alpha-d-glucopyranoside at the surface
      and triazole as bridging unit have been synthesized. Cardiomyocytes were exposed
      to normal and high glucose level in the presence and absence of glucodendrimers.
      Cytotoxicity studies were also carried out and the expression of
      metalloproteinases mainly MMP-2 and 9 was confirmed with gelatine zymography and
      RT-PCR gene expression studies. Cardio protective efficiency of the synthesized
      glucodendrimers against high glucose induced toxicity on mettalloproteinase-2 and
      9 and also on H9C2 cell lines revealed that higher generation glucodendrimers 6
      and 8 are more effective than the lower generation glucodendrimers. 

PMID- 24274525
TI  - Microwave superheated water and dilute alkali extraction of brewers' spent grain
      arabinoxylans and arabinoxylo-oligosaccharides.
AB  - Microwave superheated water extractions (MWE) were performed to evaluate the
      feasibility of this technology for quantitative recovery of the arabinoxylans
      (AX) or arabinoxylo-oligosaccharides (AXOS) from brewers' spent grain (BSG). The
      AX+AXOS yield increased with the increase of the temperature in the range from
      140 to 210  degrees C during 2 min. The higher temperatures promoted
      depolymerisation, debranching, and deesterification of the polysaccharides, with
      formation of brown products. The conditions that promote a compromise between the
      yield and the structure obtained, minimizing the thermal degradation of the
      fractions extracted by MWE are the following: (1) 140  degrees C, to remove the
      residual starch mixed with beta-glucans; (2) Suspension of the residue left in
      water and treated at 180  degrees C; (3) suspension of the residue in 0.1 M KOH
      and treated at 180  degrees C. Using this sequential procedure, it was possible
      to extract 62% of BSG AX+AXOS, presenting degrees of polymerization ranging
      between 7 and 24 xylose residues, and a degree of phenolic acids esterification
      between 5 and 21%. The structural variability obtained by MWE allows defining
      specific types of compounds for different applications and uses depending on the
      extraction conditions used.

PMID- 24274526
TI  - Dilute solution properties of carboxymethyl celluloses of various molecular
      weights and degrees of substitution.
AB  - The intrinsic viscosities of six carboxymethyl celluloses (CMC) of different
      degrees of substitution, molecular weights, and molecular weight distributions
      (MWDs) were measured as a function of pH, ionic strength, and temperature. The
      molecular weights and MWDs were determined by analytical ultracentrifugation. It
      was demonstrated that the raw viscosity data could be represented by the Fedors
      equation allowing for accurate determination of the intrinsic viscosity. Ionic
      strength, rather than pH or temperature had the strongest effect on the
      conformation of CMC. An estimate of the Mark-Houwink-Kuhn-Sakurada exponent
      (alpha=0.83) and calculations of chain flexibility and expansion factors
      indicated that CMC has semi-flexible, randomly coiling chains in solution with
      persistence lengths on the order of 8.8-24.5 nm in distilled water and 11.3-14.8
      nm in 0.01 mol/L sodium chloride. It was also found that the lowest molecular
      weight CMC was most flexible among the tested samples.

PMID- 24274527
TI  - Conformation and physical properties of cycloisomaltooligosaccharides in aqueous
      solution.
AB  - We studied the conformation and physical properties of cyclic and linear
      isomaltooligosaccharides in aqueous solution by intrinsic viscosity measurement,
      small angle X-ray scattering (SAXS) and molecular modeling. We used four
      cycloisomaltooligosaccharide samples (CIs) with degree of polymerization (DP) 7
      10 (CI-7-CI-10) and five linear isomaltooligosaccharide samples (LIs) with DP 7
      11 (LI-7-LI-11). The values of alpha in the Mark-Houwink-Sakurada equation
      [eta]=KM(w)(alpha) for the CI and LI were determined to be 0.50 and 0.78,
      respectively. The radii of gyration (R(G)) of CI-7, CI-8, CI-9 and CI-10
      determined from SAXS data were 6.7, 6.9, 7.5 and 8.3A, respectively. The
      scattering profile of CI-9 compared with those obtained for molecular models
      indicated that CI molecular chains are less flexible than those for LIs and adopt
      a rather compact circular conformation.

PMID- 24274528
TI  - Influence of water on swelling and dissolution of cellulose in 1-ethyl-3
      methylimidazolium acetate.
AB  - In this study the effect of residual coagulation medium (water) on cellulose
      dissolution in an ionic liquid is discussed. Solubility of dissolving grade pulp;
      HWP and SWP, and microcrystalline cellulose in binary solvents, mixtures of 1
      ethyl-3-methyl-imidazolium acetate and water, was investigated by turbidity
      measurements, light microscopy, rheometry, and CP/MAS (13)C-NMR spectroscopy. The
      viscoelastic properties of the cellulose solutions imply that residual water
      affect the cellulose dissolution. However, it is not obvious that this always
      necessarily poses serious drawbacks for the solution properties or that the
      effects are as severe as previously believed. Turbidity measurements, viscosity
      data and crystallinity of the regenerated cellulose correlated well and an
      increased conversion to cellulose II was found at low water and cellulose
      contents with an apparent maximum of conversion at 2-5 wt% water. At high water
      content, above 10 wt%, dissolution and conversion was largely inhibited.

PMID- 24274529
TI  - Efficient removal of lignin with the maintenance of hemicellulose from kenaf by
      two-stage pretreatment process.
AB  - The enhancement of lignocellulose hydrolysis using enzyme complexes requires an
      efficient pretreatment process to obtain susceptible conditions for the enzyme
      attack. This study focuses on removing a major part of the lignin layer from
      kenaf (Hibiscus cannabinus) while simultaneously maintaining most of the
      hemicellulose. A two-stage pretreatment process is adopted using calcium
      hydroxide, Ca(OH)2, and peracetic acid, PPA, to break the recalcitrant lignin
      layer from other structural polysaccharides. An experimental screening of several
      pretreatment chemicals, concentrations, temperatures and solid-liquid ratios
      enabled the production of an optimally designed pretreatment process for kenaf.
      Our results showed that the pretreatment process has provide 59.25% lignin
      removal while maintaining 87.72% and 96.17% hemicellulose and cellulose,
      respectively, using 1g of Ca(OH)2/L and a 8:1 (mL:g) ratio of liquid-Ca(OH)2 at
      50  degrees C for 1.5 h followed by 20% peracetic acid pretreatment at 75 
      degrees C for 2 h. These results validate this mild approach for aiding future
      enzymatic hydrolysis.

PMID- 24274530
TI  - Levan production by Zymomonas mobilis in batch and continuous fermentation
      systems.
AB  - Levan production in batch and continuous fermentation systems by Zymomonas
      mobilis B-14023 was investigated. The culture medium used in both of the
      fermentation systems contained sucrose and various organic nitrogen sources.
      Maximum concentration of levan was produced with yeast extract among the nitrogen
      sources tested. Response surface methodology was used to investigate the effects
      of three factors on the concentration of levan in batch cultures of Z. mobilis.
      Maximum levan concentration was 40.2 g/L and this concentration was reached at
      the optimum levels of process variables, which were 299.1 g/L initial substrate
      concentration, 42.3 h incubation time, and initial pH 6.0. Continuous
      fermentation experiments were done in packed bed bioreactor using Ca-alginate
      immobilized Z. mobilis cells. The highest levan concentration (31.8 +/- 0.21 g/L)
      was obtained at a dilution rate of 0.14 h(-1) while maximum volumetric
      productivity (6.556 g/(Lh)) was obtained at a dilution rate of 0.22 h(-1).
      Increasing the dilution rate resulted in decreased levan and increased residual
      sugar concentrations.

PMID- 24274531
TI  - Synthesis, characterization and applications of polymethylmethacrylate grafted
      psyllium as flocculant.
AB  - Polymethylmethacrylate grafted psyllium (Psy-g-PMMA) was synthesized by microwave
      assisted method. The grafting of the PMMA chains on the psyllium backbone was
      confirmed through the study of intrinsic viscosity, FTIR spectroscopy, elemental
      analysis, SEM and number average molecular weight (Mn). The intrinsic viscosity
      and number average molecular weight (Mn) of psyllium appreciably improved on
      grafting of PMMA chains. Further, flocculation efficacy of the graft copolymer
      was studied in kaolin suspension through jar test procedure, towards possible
      application as flocculant.

PMID- 24274532
TI  - Synthesis, characterization, and antifungal activity of novel inulin derivatives
      with chlorinated benzene.
AB  - A group of novel inulin derivatives containing benzene or chlorinated benzene
      were synthesized by reaction of chloracetyl inulin (CAIL) with the Schiff bases
      of 4-amino-pyridine, including (2-pyridyl)acetyl inulin chloride (PAIL), 2-[4-(2
      chlorobenzylideneamino)-pyridyl]acetyl inulin chloride (2CPAIL), 2-[4-(4
      chlorobenzylideneamino)-pyridyl]acetyl inulin chloride (4CPAIL), and 2-[4-(2,4
      dichlorobenzylideneamino)-pyridyl]acetyl inulin chloride (2,4DCPAIL). Their
      antifungal activity against three kinds of phytopathogens was estimated by hypha
      measurement in vitro. Of all the synthesized chitosan derivatives, 2,4DCPAIL
      inhibited the growth of the tested phytopathogens with inhibitory indices of 67%,
      47%, and 43% against Colletotrichum lagenarium (Pass) Ell.et halst, Phomopsis
      asparagi (Sacc.) Bubak and Fusarium oxysporum (schl.) F.sp. niveum (F. oxysporum)
      respectively at 1.0 mg/mL. The results indicate that all the inulin derivatives
      have better antifungal activity than inulin, and the inhibitory index is affected
      by the chlorine atom grafted to the inulin derivatives.

PMID- 24274533
TI  - HPMC as a potential enhancer of nimodipine biopharmaceutical properties via ball
      milled solid dispersions.
AB  - The poor solubility of drugs remains one of the most challenging aspects of
      formulation development. Aiming at improving the biopharmaceutical limitations of
      the calcium channel blocker nimodipine, the development of solid dispersions is
      proposed herein. Three different proportions of nimodipine:HPMC were tested and
      all of them generated amorphous solid dispersions. Improvements of up 318% in the
      solubility and a 4-fold increase in the dissolution rate of nimodipine were
      achieved. Stability studies conducted over 90 days in a desiccator indicated that
      the initial characteristic of the formulations were maintained. However, at 40 
      degrees C/75% RH recrystallization was observed for solid dispersions with 70 and
      80% of HPMC, whilst the formulation composed of 90% of the carrier remained
      amorphous. The increase in the stability observed when the HPMC concentration was
      increased from 70 to 90% in the solid dispersions was attributed to the dilution
      mechanism.

PMID- 24274534
TI  - Comparative evaluation of chitosan, cellulose acetate, and polyethersulfone
      nanofiber scaffolds for neural differentiation.
AB  - Based on accumulating evidence that the 3D topography and the chemical features
      of a growth surface influence neuronal differentiation, we combined these two
      features by evaluating the cytotoxicity, proliferation, and differentiation of
      the rat PC12 line and human neural stem cells (hNSCs) on chitosan (CS), cellulose
      acetate (CA), and polyethersulfone (PES)-derived electrospun nanofibers that had
      similar diameters, centered in the 200-500 nm range. None of the nanofibrous
      materials were cytotoxic compared to 2D (e.g., flat surface) controls; however,
      proliferation generally was inhibited on the nanofibrous scaffolds although to a
      lesser extent on the polysaccharide-derived materials compared to PES. In an
      exception to the trend toward slower growth on the 3D substrates, hNSCs
      differentiated on the CS nanofibers proliferated faster than the 2D controls and
      both cell types showed enhanced indication of neuronal differentiation on the CS
      scaffolds. Together, these results demonstrate beneficial attributes of CS for
      neural tissue engineering when this polysaccharide is used in the context of the
      defined 3D topography found in electrospun nanofibers.

PMID- 24274535
TI  - Extraction of agar from Gelidium sesquipedale (Rhodopyta) and surface
      characterization of agar based films.
AB  - The chemical structure of the agar obtained from Gelidium sesquipedale
      (Rhodophyta) has been determined by (13)C nuclear magnetic resonance ((13)C NMR)
      and Fourier transform infrared spectroscopy (FTIR). Agar (AG) films with
      different amounts of soy protein isolate (SPI) were prepared using a thermo
      moulding method, and transparent and hydrophobic films were obtained and
      characterized. FTIR analysis provided a detailed description of the binding
      groups present in the films, such as carboxylic, hydroxyl and sulfonate groups,
      while the surface composition was examined using X-ray photoelectron spectroscopy
      (XPS). The changes observed by FTIR and XPS spectra suggested interactions
      between functional groups of agar and SPI. This is a novel approach to the
      characterization of agar-based films and provides knowledge about the
      compatibility of agar and soy protein for further investigation of the functional
      properties of biodegradable films based on these biopolymers. 

PMID- 24274536
TI  - Conjugation of curcumin onto alginate enhances aqueous solubility and stability
      of curcumin.
AB  - Curcumin is a potential drug for various diseases including cancer. Prime
      limitations associated with curcumin are low water solubility, rapid hydrolytic
      degradation and poor bioavailability. In order to redress these issues we
      developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR
      and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution
      forming micelles with an average hydrodynamic diameter of 459 +/- 0.32 nm and
      negative zeta potential. The spherical micelles were visualized by TEM. The
      critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A
      significant enhancement in the aqueous solubility of curcumin was observed upon
      conjugation with alginate. Formation of micelles improved the stability of
      curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was
      quantified by MTT assay using L-929 fibroblast cells and it was found to be
      potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well
      as a nanosized delivery vehicle.

PMID- 24274537
TI  - Chitosan-caseinate bilayer coatings for paper packaging materials.
AB  - Papers coated with caseinate and caseinate/chitosan bilayer films were developed.
      Caseinate, chitosan and caseinate/chitosan films were preliminary characterized
      by FTIR spectroscopy and thermal stability analyses. The effects of coating
      weight, caseinate concentration (7%, 10%, and 12%, w/w), and coating application
      methods (single layer and bilayer) on the physical and mechanical properties of
      coated papers were studied. Increasing the concentration of caseinate led to a
      decrease in water vapor permeability (WVP) of the resulting coated paper sheets.
      Chitosan significantly (p<0.05) increased the elongation at break (%E) of coated
      paper. However, the application of chitosan as a second layer on wet or dry
      caseinate films did not significantly affect (p>0.05) the tensile strength (TS)
      of coated paper. The greatest reduction in paper WVP is achieved by addition of a
      chitosan layer to the dried preformed caseinate-coated paper. 

PMID- 24274538
TI  - Thallium(I) sorption using Prussian blue immobilized in alginate capsules.
AB  - Prussian blue (PB) was immobilized in alginate capsules. The composite sorbent
      was used for the recovery of Tl(I) ions from slightly acidic solutions: optimum
      pH being close to 4. The sorption isotherm can be described by the bi-site
      Langmuir sorption isotherm. This means that the metal ion can be bound through
      two different sorption sites: one having a strong affinity for Tl(I) (probably
      PB), the other having a lower affinity (probably the encapsulating material). The
      kinetics are described by either the pseudo-second order rate equation or the
      Crank's equation (resistance to intraparticle diffusion). The ionic strength
      (increased by addition of NaCl, KCl or CaCl2) slightly decreased sorption
      capacity. The SEM-EDX analysis of PB-alginate capsules (before and after Tl(I)
      sorption) shows that the PB is homogeneously distributed in the capsules and that
      all reactive groups remain available for metal binding.

PMID- 24274539
TI  - Neutral sugar side chains of pectins limit interactions with procyanidins.
AB  - Interactions between seven hairy regions of pectins, rhamnogalacturonans II and
      arabinogalactan-proteins and procyanidins with different average degrees of
      polymerization, low (DP9) and high (DP30), were investigated by isothermal
      titration calorimetry and absorption analysis to study the impact of neutral
      sugar side chains of pectins on these associations. Associations between pectic
      fractions and procyanidins involved hydrophobic interactions and hydrogen bonds.
      No difference in association constants between various hairy regions and
      procyanidins DP9 was found. Nevertheless, arabinan chains showed lower
      association constants, and hairy regions of pectins with only monomeric side
      chains showed higher association with procyanidin DP30. Only very low affinities
      were obtained with rhamnogalacturonans II and arabinogalactan-proteins.
      Aggregation could be observed only with the procyanidins of DP30 and the protein
      rich arabinogalactan-protein. Associations were obtained at both degrees of
      polymerization of the procyanidins, but differed depending on neutral sugar
      composition and the structure of pectic fractions. 

PMID- 24274540
TI  - Characterization of antioxidant-antibacterial quince seed mucilage films
      containing thyme essential oil.
AB  - In this study thyme essential oil (TEO) concentrations ranging from 0% to 2.0%,
      incorporated in quince seed mucilage (QSM) film were used. Antibacterial
      activity, physical, mechanical, barrier and antioxidant properties of QSM films
      were evaluated. The antimicrobial activity of the QSM films incorporated with
      thyme essential oil was screened against 11 important food-related bacterial
      strains by agar disc-diffusion assay. Films containing 1% of thyme essential oil
      were effective against all test microorganisms and exhibited a strong inhibitory
      effect on the growth of Shewanella putrefaciens, Listeria monocytogenes and
      Staphylococcus aureus. QSM films exhibited some antioxidant activity, which was
      significantly improved by the addition of the essential oil. A reduction of the
      glass transition temperature, as determined by differential scanning calorimetry
      (DSC), was caused by addition of thyme essential oil into the QSM films. Scanning
      electron microscopy was carried out to explain structure-property relationships.
      Incorporating thyme essential oil into edible QSM films provides a novel way to
      improve the safety and shelf life of ready-to-eat foods. 

PMID- 24274541
TI  - Detection of keratan sulfate by immunological methods in commercial chondroitin
      sulfate preparations.
AB  - Chondroitin sulfate (CS), a well known nutraceutical, and keratan sulfate (KS)
      are glycosaminoglycans involved in the structure of cartilage proteoglycan,
      aggrecan. Since CS is extracted from cartilage, there may be a possibility that
      purified CS is contaminated with small amount of KS. A total of 15 samples,
      including four samples of CS as laboratory reagents, one sample of CS as a food
      additive and ten samples of dietary supplements containing CS were examined to
      detect KS in these samples by using immunodiffusion and enzyme-linked
      immunosorbent assay (ELISA) with anti-KS monoclonal antibody (IgM). With the
      exception of three samples of CS as laboratory reagents, all samples were found
      to contain varying amounts of KS. It was concluded that both the immunodiffusion,
      a quick one-step method, and ELISA for quantification, are reliable methods to
      detect KS contamination in CS products. 

PMID- 24274542
TI  - Preparation of polysaccharides from cyanobacteria Nostoc commune and their
      antioxidant activities.
AB  - In this study, water soluble polysaccharides were prepared from cyanobacteria
      Nostoc commune by water extraction. Factors affecting the polysaccharide yields
      were investigated, and the optimum extraction conditions were determined as
      follows: time, 4h; temperature, 90  degrees C; the ratio of liquid to solid, 60:1
      (v/w); and extraction times, 4. The extract was filtered, concentrated to ~10%
      (w/v), precipitated with 3 volumes of ethanol, freeze-dried, and ground to yield
      a water soluble power. The polysaccharide content of the product was 96.7%, and
      the yield was 9.18% (w/w). Fourier transform infrared spectra demonstrated that
      the product samples were mainly composed of polysaccharides. The polysaccharides
      showed high hydroxyl radical scavenging activity (92.71%) and reducing capacity
      (0.445) at the concentration of 10 mg/mL.

PMID- 24274543
TI  - Thermodynamic and kinetic study of volatile compounds in biopolymer based
      dispersions.
AB  - Partitioning and release of ethyl acetate and diacetyl from two matrices with a
      different composition was studied by applying static head space gas
      chromatography. Two matrices with a different composition have been developed:
      one containing carbohydrates (Tragacanth gum) and in the second one, called
      complex matrix, a lipid (oleic acid) was added. The roles of carbohydrate
      (Tragacanth gum) and lipid (oleic acid) on the retention of all the aroma
      compounds were pointed out. Changes in the composition of matrices exhibited a
      considerable effect on the thermodynamic component as expressed by the air/liquid
      partition coefficient (Ka/l) values at equilibrium (20  degrees C). The kinetic
      study of the release from these matrices had shown a decrease of the initial rate
      of release (Ri) by reference with water. The rheological properties of all
      matrices were investigated and the flow behaviour of all matrices was
      successfully modelled with power law and Ellis models and power law model was
      found as the better model to describe the flow behaviour of dispersions.

PMID- 24274544
TI  - Effect of nitric acid on pretreatment and fermentation for enhancing ethanol
      production of rice straw.
AB  - In this study, nitric acid (HNO3) was evaluated as an acid catalyst for rice
      straw pretreatment, and, after neutralization, as a sole nitrogen source for
      subsequent fermentation. Response surface methodology was used to obtain optimal
      pretreatment condition with respect to HNO3 concentration (0.2-1.0%), temperature
      (120-160  degrees C) and reaction time (1-20 min). In a condition of 0.65% HNO3,
      158.8  degrees C and 5.86 min, a maximum xylose yield of 86.5% and an enzymatic
      digestibility of 83.0% were achieved. The sugar solution that contained nitrate
      derived from the acid catalyst supported the enhancement of ethanol yield by
      Pichia stipitis from 10.92 g/L to 14.50 g/L. The results clearly reveal that
      nitric acid could be used not only as a pretreatment catalyst, but also as a
      nitrogen source in the fermentation process for bioethanol production. It is
      anticipated that the HNO3-based pretreatment can reduce financial burden on the
      cellulosic bioethanol industry by simplifying after-pretreatment-steps as well as
      providing a nitrogen source.

PMID- 24274546
TI  - Improving the performance of starch-based wood adhesive by using sodium dodecyl
      sulfate.
AB  - Sodium dodecyl sulfate (SDS) was used to improve the performance of starch-based
      wood adhesive. The effects of SDS on shear strength, viscosity and storage
      stability were investigated. It was shown that, although the addition of 1.5-2%
      (dry starch basis) SDS resulted in a slight decrease in shear strength, the
      mobility and storage stability of adhesive were significantly enhanced. Possible
      mechanisms regarding specific action of SDS were discussed. It was proved, using
      blue value or differential scanning calorimetry (DSC) analysis, that the amylose
      SDS complexes were formed in the adhesive. The complex formation or simple
      adsorption of SDS with starch molecules might hinder the aggregation of latex
      particles, as shown by scanning electron microscopy images, and inhibit starch
      retrogradation, as observed by DSC analysis. As a result, in the presence of SDS,
      the adhesive had higher mobility and storage stability, indicating that SDS could
      be used to prepare starch-based wood adhesives with high performance. 

PMID- 24274545
TI  - Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-kappaB and
      endothelial inflammatory response.
AB  - It is known that chitosan oligosaccharides (COS) suppress LPS-induced vascular
      endothelial inflammatory response by mechanism involving NF-kappaB blockade. It
      remains unknown how COS inhibit NF-kappaB. We provided evidence both in cultured
      endothelial cells and mouse model supporting a new mechanism. Regardless of the
      endothelial cell types, the LPS-induced NF-kappaB-dependent inflammatory gene
      expression was suppressed by COS, which was associated with reduced NF-kappaB
      nucleus translocation. LPS enhanced O-GlcNAc modification of NF-kappaB/p65 and
      activated NF-kappaB pathway, which could be prevented either by siRNA knockdown
      of O-GlcNAc transferase (OGT) or pretreatment with COS. Inhibition of either
      mitogen-activated protein kinase or superoxide generation abolishes LPS-induced
      NF-kappaB O-GlcNAcylation. Consistently, aortic tissues from LPS-treated mice
      presented enhanced NF-kappaB/p65 O-GlcNAcylation in association with upregulated
      gene expression of inflammatory cytokines in vascular tissues; however, pre
      administration of COS prevented these responses. In conclusion, COS decreased OGT
      dependent O-GlcNAcylation of NF-kappaB and thereby attenuated LPS-induced
      vascular endothelial inflammatory response. 

PMID- 24274547
TI  - Preparation and characterization of polysaccharides/PVA blend nanofibrous
      membranes by electrospinning method.
AB  - A series of polyvinyl alcohol (PVA), PVA/chitosan (CS) and PVA/cyanobacterial
      extracellular polymeric substances (EPS) blended nanofibrous membranes were
      produced by electrospinning using a microfiltration poly(vinylidene fluoride)
      (PVDF) basal membrane, for potential applications in water filtration. Nanofibres
      were obtained from solutions of 20% (w/w) PVA with 1% (w/w) CS or EPS, using a
      weight ratio of 60/40. Blended nanofibres have shown a smooth morphology, no
      beads formation and diameters between 50 and 130 nm. Thermo-mechanical analysis
      demonstrated that there were inter and/or intramolecular hydrogen bonds between
      the molecules of PVA/CS and PVA/EPS in the blends. The electrospun blended
      PVA/EPS membrane showed better tensile mechanical properties when compared with
      PVA and PVA/CS, and resisted more against disintegration in the temperature range
      between 10 and 50  degrees C. Finally, the blended membranes have shown an
      increase in chromium binding capacity of 5%. This is the first successful report
      of a blended membrane of electrospinned cyanobacterial polysaccharide with PVA.

PMID- 24274548
TI  - Chitosan based grey wastewater treatment--a statistical design approach.
AB  - In this present study, grey wastewater was treated under different operating
      conditions such as agitation time (1-3 min), pH (2.5-5.5), chitosan dose (0.3
      0.6g/l) and settling time (10-20 min) using response surface methodology (RSM).
      Four factors with three levels Box-Behnken response surface design (BBD) were
      employed to optimize and investigate the effect of process variables on the
      responses such as turbidity, BOD and COD removal. The results were analyzed by
      Pareto analysis of variance (ANOVA) and second order polynomial models were
      developed in order to predict the responses. Under the optimum conditions,
      experimental values such as turbidity (96%), BOD (91%) and COD (73%) removals are
      closely agreed with predicted values.

PMID- 24274549
TI  - Gellan-thioglycolic acid conjugate: synthesis, characterization and evaluation as
      mucoadhesive polymer.
AB  - Gellan-thioglycollic acid conjugate was synthesized with the objective to improve
      its mucoadhesive properties. Synthesis of conjugate was confirmed by -SH stretch
      in the Fourier-transform infrared spectra at 2571 cm(-1). It was found to contain
      13.92 mM of thiol groups/g of the conjugate. Thiolation of gellan gum was found
      to slightly increase its degree of crystallinity and decrease its sensitivity to
      Ca(2+)-induced gelation. On screening of gellan-thioglycollic acid conjugate for
      ex-vivo ocular tolerance using hen's egg chorio-allantoic membrane test and for
      biocompatibility by resazurin assay on Vero-cells, it was found to be non
      irritant and biocompatible. Metronidazole gels formulated using gellan
      thioglycollic acid conjugate as bioadhesive agent showed 1.82-fold higher
      mucoadhesive strength than the gels formulated using gellan gum. Further, the
      metronidazole gels containing gellan and gellan-thioglycollic conjugate released
      the drug following first-order and Higuchi's square-root release kinetics. In
      conclusion, gellan-thioglycollic acid conjugate is a promising bioadhesive
      excipient.

PMID- 24274550
TI  - Preparation of microcapsules by complex coacervation of gum Arabic and chitosan.
AB  - Gum Arabic-chitosan microcapsules containing a commercially available blend of
      triglycerides (Miglyol 812 N) as core phase were synthesized by complex
      coacervation. This study was conducted to clarify the influence of different
      parameters on the encapsulation process, i.e. during the emulsion formation steps
      and during the shell formation, using conductometry, zeta potential, surface and
      interface tension measurement and Fourier-transform infrared spectroscopy. By
      carefully analyzing the influencing factors including phase volume ratio,
      stirring rate and time, pH, reaction time, biopolymer ratio and crosslinking
      effect, the optimum synthetic conditions were found out. For the emulsion step,
      the optimum phase volume ratio chosen was 0.10 and an emulsion time of 15 min at
      11,000 rpm was selected. The results also indicated that the optimum formation of
      these complexes appears at a pH value of 3.6 and a weight ratio of chitosan to
      gum Arabic mixtures of 0.25.

PMID- 24274551
TI  - TEMPO-mediated oxidation of oat beta-D-glucan and its influences on paper
      properties.
AB  - An enhanced bonding agent for papermaking was prepared by selective oxidation of
      a hemicellulose-rich byproduct of oat processing, which will be identified here
      by its primary component, beta-D-glucan. The beta-D-glucan was treated
      sequentially with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) and sodium
      hypochlorite, or alternatively just with sodium hydroxide. When added to a slurry
      of unbleached softwood kraft fibers, in combination with an optimal dosage of
      aluminum sulfate, the oxidized beta-D-glucan yielded greater increases in tensile
      strength and folding endurance in comparison to untreated beta-D-glucan. NaOH
      treatment also improved dry-strength performance of the beta-D-glucan, except for
      folding endurance. The improvements were attributed to increased charge density
      of the treated polyelectrolytes, leading to better distribution and retention on
      fibers prior to sheet formation. Modified beta-D-glucan also enhanced the
      strength of recycled sheets when the treated paper was repulped and formed into
      recycled paper with no further chemical addition.

PMID- 24274552
TI  - Sulphation can enhance the antioxidant activity of polysaccharides produced by
      Enterobacter cloacae Z0206.
AB  - The protective effects of sulfated polysaccharide derivatives produced by
      Enterobacter cloacae Z0206 against H2O2-induced oxidative damage in RAW264.7
      murine macrophages as well as the possible mechanisms governing the protective
      effects were studied. Sulfated polysaccharides protected RAW264.7 cells from
      oxidative damage and apoptosis induced by H2O2 by protecting the cellular
      structure; improving the activity of antioxidant enzymes, such as superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px); and inhibiting caspase-3
      activation and DNA fragmentation. In addition, the sulfated polysaccharides
      conferred higher levels of protection from H2O2-induced oxidative damage in
      RAW264.7 murine macrophages compared to the native polysaccharide lacking
      sulfation. These results indicated that sulfated modifications might be an
      effective approach to enhance the antioxidant activity of polysaccharides
      produced by E. cloacae Z0206, and the sulfated derivatives of these
      polysaccharides may act as potent antioxidant agents.

PMID- 24274553
TI  - Phase behavior of concentrated hydroxypropyl methylcellulose solution in the
      presence of mono and divalent salt.
AB  - Thermo reversible sol-gel transitions of hydroxypropylmethylcellulose (HPMC) are
      critical for many pharmaceutical, cosmetic, and food applications. This study
      examined the effects of salt (NaCl and CaCl2) on the viscoelastic properties of
      concentrated low molecular weight HPMC solutions and found that the gelation
      temperature decreased linearly as a function of salt concentrations, independent
      of valency of cations and the mole concentration of anions. Thermal analysis
      showed that the depression of melting temperature can be fitted for both NaCl and
      CaCl2 as a function of the total number of ions by a single linear curve, which
      was consistent with the melting point depression of pure water by NaCl and CaCl2,
      but with a higher linear slope.

PMID- 24274554
TI  - Interactions between fluorinated cationic guar gum and surfactants in the dilute
      and semi-dilute solutions.
AB  - The interactions between the fluorinated cationic guar gum (FCGG) and ionic
      surfactants including cetyl trimethyl ammonium bromide (CTAB) and sodium lauryl
      sulfate (SDS) were studied by light scattering, fluorescence spectroscopy, UV
      spectrophotometer, (19)F NMR and dynamic rheometer, respectively. The FCGG is
      prepared with cationic guar gum, isophorone diisocyanate and 2,2,3,4,4,4
      hexafluoro-1-butanol. The results show that, with the addition of the
      surfactants, the stretching degree of the FCGG chains is increased in the
      FCGG/CTAB solutions, while the dramatical shrinking of FCGG chain, the phase
      separation and the re-stretched macromolecules appear successively because of the
      electricity neutralization reaction in the FCGG/SDS system. The mixed hydrophobic
      domains in all solutions will be reinforced and then dismantled. The solution
      elasticity shows up the maximum value accordingly. The surfactants can be
      embedded in the micro-domains and then hinder the fluorinated segmental motions.
      The interactions between FCGG and SDS are much stronger than those between FCGG
      and CTAB. 

PMID- 24274555
TI  - Preparation and antioxidant activity of Lycium barbarum oligosaccharides.
AB  - In this study, the Lycium barbarum oligosaccharides (LBO) were prepared by
      hydrolysis using hydrogen peroxide (H2O2). The yield of the LBO was monitored
      during the hydrolysis process. The hydrolysis conditions were optimized as
      follows: time, 4h; temperature, 70  degrees C; and H2O2 concentration, 2.5%
      (v/v). The hydrolysates were filtered, concentrated to ~20% (w/v), precipitated
      with 6 volumes of absolute ethanol, freeze-dried, and ground to yield a water
      soluble and white powder. The sugar content of the product was 95.8%, and the
      yield was 21.05% (w/w), respectively. The LBO show higher hydroxyl radical
      scavenging activity (86.46%) than Vc (40.96) at the concentration of 100 MUg/mL.

PMID- 24274556
TI  - Production and modification of nanofibrillated cellulose using various mechanical
      processes: a review.
AB  - Nanofibrillated cellulose from biomass has recently gained attention owing to
      their biodegradable nature, low density, high mechanical properties, economic
      value and renewability. Although they still suffer from two major drawbacks. The
      first challenge is the exploration of raw materials and its application in
      nanocomposites production. Second one is high energy consumption regarding the
      mechanical fibrillation. However, pretreatments before mechanical isolation can
      overcome this problem. Hydrophilic nature of nano-size cellulose fibers restricts
      good dispersion of these materials in hydrophobic polymers and therefore, leads
      to lower mechanical properties. Surface modification before or after mechanical
      defibrillation could be a solution for this problem. Additionally, drying affects
      the size of nanofibers and its properties which needs to study further. This
      review focuses on recent developments in pretreatments, nanofibrillated cellulose
      production and its application in nanopaper applications, coating additives,
      security papers, food packaging, and surface modifications and also for first
      time its drying. 

PMID- 24274557
TI  - Synthesis, characterization, swelling and drug release behavior of semi
      interpenetrating network hydrogels of sodium alginate and polyacrylamide.
AB  - Several semi interpenetrating network (SIPN) type hydrogels were synthesized by
      in-situ free radical crosslink copolymerization of acrylamide and crosslinker
      N,N'-methylene bisacrylamide (MBA) in aqueous solution of sodium alginate
      (SA).These SIPN hydrogels were characterized by FTIR, NMR SEM, DTA-TGA, XRD, PZC
      and also by swelling characteristics and network parameters. Adsorption (loading)
      and release of acetaminophen drug were studied with these hydrogels. Solution pH,
      crosslinker concentration and monomer to SA weight ratio of the hydrogels were
      found to have a strong effect on adsorption and in vitro release profile of the
      drug from the gel matrix. 

PMID- 24274558
TI  - Modulating the structural properties of beta-D-glucan degradation products by
      alternative reaction pathways.
AB  - The aim of the present study was to compare the degradation of beta-D-glucan
      induced by hydroxyl radical to the degradation induced by heat treatment. beta-D
      Glucan was quickly and widely degraded by the action of hydroxyl radicals
      produced by a Fenton system at 85  degrees C, while thermal hydrolysis at 85 
      degrees C induced slow beta-D-glucan depolymerization. The hydroxyl radical
      induced degradation of beta-D-glucan was accompanied by the formation of peroxyl
      radicals and new oxidized functional groups (i.e. lactones, carboxylic acids,
      ketones and aldehydes), as detected by ESR and NMR, respectively. In contrast, no
      changes in the monomer chemical structure of beta-D-glucan were observed upon
      thermal hydrolysis. Therefore, different mechanisms are proposed for the
      oxidative cleavage of beta-D-glucan, which are initiated by the presence of an
      unpaired electron on the anomeric carbon.

PMID- 24274559
TI  - Selected properties of acetylated adipate of retrograded starch.
AB  - Native potato starch (NS) and retrograded starch (R - obtained via freezing and
      defrosting of a starch paste) were used to prepare starch acetates: NS-A and R-A,
      and then acetylated distarch adipates: NS-ADA and R-ADA. The chemically-modified
      preparations produced from retrograded starch (R-A; R-ADA) were characterized by
      a higher degree of esterification compared to the modified preparations produced
      under the same conditions from native potato starch (NS-A; NS-ADA). Starch
      resistance to amylolysis was observed to increase (to 30-40 g/100 g) as a result
      of starch retrogradation and acetylation. Starch cross-linking had a significant
      impact on the increased viscosity of the paste in the entire course of pasting
      characteristics and on the increased values of rheological coefficients
      determined from the equations describing flow curves. The produced preparation of
      acetylated retrograded starch cross-linked with adipic acid (R-ADA) may be deemed
      an RS3/4 preparation to be used as a food thickening agent.

PMID- 24274560
TI  - Exopolymers from Tolypothrix tenuis and three Anabaena sp. (Cyanobacteriaceae) as
      novel blood clotting agents for wound management.
AB  - Rapid initiation of clotting is critical to trauma patients. In the present study
      exopolymers (EPs) from four desert cyanobacteria including Tolypothrix tenuis and
      three species of Anabaena have been discovered as potential hemostatic
      biomaterials. The EPs showed reduction in activated partial thromboplastin time
      (APTT) and prothrombin time (PT) by 16-41% and 12-65%, respectively. Besides
      hastening blood clotting, the EPs could absorb 7.1-25.9 g H2O g(-1) EP and
      displayed 7.1-18.1% hydrophobicity. They were noncytotoxic and biodegradable. The
      EP from Anabaena sp. showed strong antibacterial activity against E. coli, S.
      aureus and B. licheniformis. These results suggest that cyanobacteria, the
      microscopic phototrophs growing rapidly over simple mineral medium could prove to
      be a novel source of affordable hemostatic dressings for the traumatic wounds in
      underdeveloped and developing countries. Compositional analysis of the EPs showed
      them to be consisting of mainly carbohydrate (17-50%), protein (4.4-7.2%), uronic
      acid (4.7-9.5%) and sulphate (0.6-6.6%). Their viscometric molecular weight
      ranged from 539 to 3679 kDa. They were further characterized using GC-MS and
      FTIR.

PMID- 24274561
TI  - Osteogenesis induction of periodontal ligament cells onto bone morphogenic
      protein-2 immobilized PCL fibers.
AB  - The purpose of this study was to develop bone morphogenic protein-2 (BMP-2)
      immobilized PCL fibers to induce osteogenic differentiation of periodontal
      ligament cells (PDLCs). The PCL fiber surface was modified with heparin-dopamine
      (Hep-DOPA) (Hep-PCL) and further immobilized with BMP-2 (BMP-2/Hep-PCL). PCL
      fibers and surface-modified PCL fibers (Hep-PCL and BMP-2/Hep-PCL) were
      characterized by X-ray photoelectron spectroscopy (XPS) and contact angle.
      Osteogenic differentiation of PDLCs was demonstrated by alkaline phosphatase
      (ALP) activity, calcium deposition, and gene expression. The results of XPS and
      contact angle revealed that Hep-DOPA and BMP-2 were successfully immobilized onto
      the PCL surface and that the BMP-2/Hep-PCL fibers have more hydrophilic surface
      properties than PCL fibers alone. ALP activity, calcium deposition, and gene
      expression on BMP-2/Hep-PCL fibers showed significantly induced osteogenic
      differentiation relative to PCL fibers. Therefore, we suggest that BMP-2/Hep-PCL
      fibers have the potential to effectively induce osteogenic differentiation of
      PDLCs. 

PMID- 24274562
TI  - Amphiphilic polyesters bearing pendant sugar moieties: synthesis,
      characterization, and cellular uptake.
AB  - Ring-opening polymerization (ROP) and "click" reactions were used to prepare a
      series of amphiphilic block-graft (PalphaN3CL-g-Sugar)-b-PCL polymers. The
      glycosylated RO-(PalphaN3CL-g-Sugar)-b-PCL polymers formed micelles with critical
      micelle concentrations (CMCs) in the range of 4.9-23.2 mg L(-1) in the aqueous
      phase. The mean diameters of the micelles were between 21 nm and 125 nm,
      considerably lower than the 200 nm diameter at which the uptake of micelles by
      the reticuloendothelial cells becomes compromised. Selective lectin-binding
      experiments confirmed that glycosylated RO-(PalphaN3CL-g-Sugar)-b-PCL can be used
      in biorecognition applications, and in vitro cell-viability assay showed that RO
      (PalphaN3CL-g-Sugar)-b-PCL has low cytotoxicity. Micelles loaded with doxorubicin
      (DOX) facilitated an improved uptake of DOX by HeLa cells that was completed
      within 1h, and the endocytosed-DOX successfully reached intracellular
      compartments and entered nuclei.

PMID- 24274563
TI  - Synthesis and characterization of biotin modified cholesteryl pullulan as a novel
      anticancer drug carrier.
AB  - A series of biotin modified cholesteryl pullulan (Bio-CHSP) conjugates with
      different degrees of substitution (DS) of biotin moiety were synthesized and
      characterized by Fourier transform infrared (FT-IR), proton nuclear magnetic
      resonance ((1)H NMR) and X-ray diffraction (XRD). Bio-CHSP conjugates were
      amphiphilic in nature and their self-aggregation behavior in aqueous media was
      evaluated by the fluorescence probe technique. Bio-CHSP self-aggregated
      nanoparticles (Bio-CHSP NPs) were prepared and analyzed by dynamic light
      scattering (DLS), zeta potential and transmission electron microscopy (TEM)
      technologies. These novel nanoparticles were almost spherical in shape, and their
      size, ranging from 178.8 to 100.0 nm. The safety of Bio-CHSP NPs was studied
      through single dose toxicity test in mice, and the result showed that Bio-CHSP
      NPs were well tolerated at the intravenous dose of 200 mg/kg in mice. Moreover,
      as a model anticancer drug, mitoxantrone loaded Bio-CHSP NPs were also prepared
      and characterized in this study.

PMID- 24274564
TI  - Synthesis and properties of novel biomimetic and thermo-responsive dextran-based
      biohybrids.
AB  - A new class of biodegradable, biomimetic and thermo-responsive dextran/synthetic
      glycopolymer biohybrids (dextran-graft-poly(lactobionamidoethyl methacrylate)
      block-poly(di(ethylene glycol) methyl ether methacrylate), dextran-g-(PLAMA-b
      PDEGMA)), was synthesized by the direct atom transfer radical polymerization
      (ATRP) of unprotected lactobionamidoethyl methacrylate (LAMA) glycomonomer and
      di(ethylene glycol) methyl ether methacrylate (DEGMA) monomer. The dextran
      macroinitiator for ATRP was prepared by partial esterification of the hydroxyl
      groups of the polysaccharide with 2-bromo-2-methylpropionic acid (BrMPA). The
      biohybrids containing PDEGMA segments exhibited a lower critical solution
      temperature (LCST) behavior, which changed from unimers to aggregates in
      solutions. Moreover, it was demonstrated that these biohybrids had specific
      biomolecular recognition with ricinus communis agglutinin 120 (RCA120) in
      comparison with bovine serum albumin (BSA). Furthermore, these biohybrids showed
      good biocompatibility in the cytotoxicity assays. This hopefully provides a
      platform for targeted drug delivery and studying the biomolecular recognition
      between sugar and lectin.

PMID- 24274565
TI  - Structure of glycoproteins from Acacia gum: an assembly of ring-like
      glycoproteins modules.
AB  - The glycoprotein (GP) molecular fraction structure of the gum exudate of Acacia
      senegal (gum Arabic) isolated from hydrophobic interaction chromatography was
      investigated using high-performance size exclusion chromatography-multi angle
      laser light scattering (HPSEC-MALLS), small angle X-ray scattering (SAXS),
      synchrotron radiation circular dichroism (SRCD) and transmission electron
      microscopy (TEM) observations. In solution, GP would be a mixture of spheroidal
      monomers and more anisotropic oligomers as suggested by the two exponent values
      found in the Rg vs. Mw relationship and TEM observations. The GP conformation
      probed by SAXS was ascribed to a thin object with a triaxial ellipsoid
      morphology, certainly attributed to GP oligomers. A 9 nm diameter particle was
      also identified by SAXS in agreement with the dimensions identified by TEM on
      single isolated ring-like structures. The GP oligomerization process, as probed
      by TEM, would be the result of ring-like subunits self-association. This self
      association would lead to more linear or, sometimes, cyclised assembly. At the
      molecular level, GP fraction was found to have secondary structures mainly made
      of beta-sheets and turns (64%) but also, to a lesser extent, made of polyproline
      II (PPII) and alpha-helices (19%). These features were characteristic of
      hydroxyprolin-rich glycoproteins with arabinosylated and arabinogalactan
      polysaccharide side chains grafted to the polypeptide backbone. The GP molecular
      fraction structure from Acacia gum would be an assembly of ring-like
      glycoproteins modules. These ring-like structures were certainly due to
      hydroxyproline (Hyp)-arabinogalactan (AG) subunits.

PMID- 24274566
TI  - Synthesis and characterization of photochromic azobenzene cellulose ethers.
AB  - Photochromic azobenzene cellulose ethers were prepared by homogeneous
      etherification of cellulose with 2,3-epoxypropoxy-azobenzene (EA) in N,N
      dimethylacetamide/lithium chloride solution. The EA with epoxy group could highly
      efficiently react with cellulose to synthesize 3-azobenzyloxy-2-hydroxypropyl
      cellulose (Azo-cellulose) ethers with controllable degree of substitution
      (DS(azo)). The DS(azo) was in a range of 0.2-2.0 adjusted by the molar ratio of
      EA to anhydroglucose unit of cellulose. The Azo-celluloses with DS(azo)>=0.53
      were soluble in aprotic solvents like dimethylsulfoxide. Their chemical
      structures and properties were characterized by elemental analysis, FT-IR, NMR,
      and thermogravimetric analysis. They showed reversible trans-cis-trans transition
      when Azo-cellulose/DMAc solutions were irradiated by successive irradiation of UV
      and visible light. The transition between trans- and cis- isomers could be
      effectively controlled by simply adjusting the irradiation time. The photo
      stimulated trans-cis-trans conformational change induced conformation transition
      between rod-like shape of trans-isomer and skewed shape of cis-isomer.

PMID- 24274567
TI  - Cationised O-acetyl galactoglucomannans: synthesis and characterisation.
AB  - Water-soluble O-acetyl-galactoglucomannans (GGMs) can be obtained from Norway
      spruce by hot-water-extraction of the wood or as a side product by
      ultrafiltration of mechanical pulping waters. Cationic and amphiphilic
      polysaccharides and their derivatives are of interest for a number of
      applications and thus quaternary nitrogen moieties with cationic charge were
      grafted onto GGMs in the heterogeneous reaction to render a cationic
      polyelectrolyte. The degree of substitution was measured by elemental analysis of
      nitrogen, by quantitative (13)C NMR and interestingly also by polyelectrolyte
      titration and the results were congruent. NMR, matrix-assisted laser
      desorption/ionisation mass spectroscopy (MALDI-TOF-MS), and FT-IR analysis were
      used to characterise the product. THF or DMSO with water enhanced the reaction
      efficiency and decreased M(w) reduction in comparison to plain water as a
      reaction media. Cationised GGM was also successfully acetylated. The cationic
      derivatives of hemicelluloses can potentially be utilised as polyelectrolyte
      layers in packaging and pharmaceutical applications.

PMID- 24274568
TI  - Purification, antioxidant activity and antiglycation of polysaccharides from
      Polygonum multiflorum Thunb.
AB  - Polysaccharides, one of the most important constituents in Polygonum multiflorum
      Thunb, a famous Chinese medicinal herb, were isolated by DEAE-52, Sepharose 4B
      and Sephacryl S-300 column chromatography. Two polysaccharides (PMP-1 and PMP-2)
      were identified as homogeneous in molecular weight with HPLC. The molecular
      weights were 4.8 * 10(2) and 6.1 * 10(2) kDa, respectively. Antioxidant activity
      tests were performed with two polysaccharides at concentrations of 0.1-1.5mg/mL.
      The results indicated that the inhibitory activity on oxidation and glycation
      exhibited a dose-dependent response. PMP-2 exhibited a much stronger antioxidant
      capacity against free radical, lipid oxidation and protein glycation. The IC50
      values of PMP-2 were 0.47, 0.6 and 0.93 mg/mL for superoxide anion scavenging,
      hydroxyl radical scavenging, and hydroxyl peroxide scavenging, respectively. The
      inhibitory ability of PMP-2 on lipid oxidation was most markedly in rat liver,
      followed by heart and kidney. Meanwhile, PMP-2 also showed satisfactory
      suppression of AGEs formation. This suggested that the polysaccharides present in
      PM can contribute to the biological effects.

PMID- 24274569
TI  - Antioxidant and immunostimulant beta-glucan from edible mushroom Russula
      albonigra (Krombh.) Fr.
AB  - A water soluble beta-glucan (PS) with an average molecular weight ~1.95 * 10(5)Da
      was isolated from the alkaline extract of ectomycorrhizal edible mushroom,
      Russula albonigra (Krombh.) Fr. and found to consist of terminal, (1 -> 3)-, (1 
      > 6)-, and (1 -> 3,6)-linked beta-D-glucopyranosyl moieties in a ratio of nearly
      1:2:2:1. The structure of this PS was elucidated on the basis of total
      hydrolysis, methylation analysis, Smith degradation, partial hydrolysis, and
      1D/2D NMR experiments. On the basis of these experiments, the repeating unit of
      the PS was found to contain a backbone of three (1 -> 6)-beta-D-glucopyranosyl
      residues, one of which was branched at O-3 position with the side chain
      consisting of two (1 -> 3)-beta-D-glucopyranosyl and a terminal beta-D
      glucopyranosyl residue. This PS showed in vitro macrophage activation by NO
      production as well as splenocytes and thymocytes proliferation. Moreover, it also
      exhibited potent antioxidant activities.

PMID- 24274570
TI  - Reduction of thrombogenicity of PVC-based sodium selective membrane electrodes
      using heparin-modified chitosan.
AB  - Heparin-modified chitosan (H-chitosan) membrane was utilized to enhance
      biocompatibility of sodium selective membrane electrode based on the highly
      thrombogenic polyvinyl chloride (PVC). Sodium ion sensing film was prepared using
      PVC, sodium ionophore-X, potassium tetrakis(chlorophenyl)-borate, and o
      nitrophenyloctylether. The PVC-based sensing film was sandwiched to chitosan or H
      chitosan to prevent platelet adhesion on the surface of PVC. Potentiometric
      response characteristics of PVC-chitosan and PVC-H-chitosan membrane electrodes
      were found to be comparable to that of a control PVC based sodium-selective
      electrode. This indicates that chitosan and H-chitosan layers do not alter the
      response behaviour of the PVC-based sensing film. Biocompatibility of H-chitosan
      was confirmed by in vitro platelet adhesion study. The platelet adhesion
      investigations indicated that H-chitosan film is less thrombogenic compared to
      PVC, which could result in enhancement of biocompatibility of sodium selective
      membrane electrodes based on PVC, while maintaining the overall electrochemical
      performance of the PVC-based sensing film. 

PMID- 24274571
TI  - Enhanced enzymatic hydrolysis of pretreated almond-tree prunings for sugar
      production.
AB  - Almond-tree prunings (ATP), an agricultural residue largely available in
      Mediterranean countries, were pretreated with either hot water or dilute
      sulphuric acid at 180-230  degrees C. Solids derived from hot water pretreatments
      were further submitted to alkaline peroxide delignification. In addition, all
      solids obtained from the three mentioned processes were hydrolysed by cellulases
      and beta-glucosidases to investigate their enzymatic digestibilities. Hot water
      pretreatment led to high oligosaccharide yields (18.2 g/100 g ATP at 190  degrees
      C) while dilute acid pretreatment provided the highest monosaccharide yields
      (24.0 g/100 g ATP at 190  degrees C) along with low concentrations of
      fermentation inhibitors. Glucose yields from enzymatic hydrolysis were strongly
      affected by both pretreatment type and pretreatment temperature. The highest
      temperature assayed for both hydrothermal and dilute sulphuric acid pretreatment
      maximized the glucose recovery (49.2% and 72.8%, respectively) while solids
      derived from alkaline peroxide treatment achieved maximal glucose concentrations
      (41.9 g/L, 58.4% of potential yield).

PMID- 24274572
TI  - Arabinoxylan from finger millet (Eleusine coracana, v. Indaf 15) bran:
      purification and characterization.
AB  - Water unextractable portion from finger millet bran was sequentially extracted
      with saturated barium hydroxide (BE) and 1M potassium hydroxide (KE) solutions.
      They consisted preponderantly of arabinose and xylose in different ratios.
      Ferulic, caffeic, coumaric and vanillic acids were identified as major bound
      phenolic acids. BE and KE were purified on DEAE-cellulose column by eluting
      successively with different eluants. The major fractions (0.1 M ammonium
      carbonate) were resolved into one (BE) and two subfractions (KE1 and KE2)
      respectively on Sephacryl S-400 gel filtration chromatography and their
      homogeneity was ascertained by gel filtration, cellulose acetate membrane
      electrophoresis and capillary electrophoresis. The average molecular weight of
      BE, KE1 and KE2 were found to be 430, 1028 and 40 kDa respectively. The
      structural elucidation of the purified polysaccharides by (1)H and (13)C NMR
      analysis indicated the backbone to be 1,4-beta-D-linked xylan with substitution
      mainly at O-2 or O-3 and/or both by alpha-l-arabinose residues.

PMID- 24274573
TI  - One-step synthesis of size-tunable Ag nanoparticles incorporated in electrospun
      PVA/cyclodextrin nanofibers.
AB  - One-step synthesis of size-tunable silver nanoparticles (Ag-NP) incorporated into
      electrospun nanofibers was achieved. Initially, in situ reduction of silver salt
      (AgNO3) to Ag-NP was carried out in aqueous solution of polyvinyl alcohol (PVA).
      Here, PVA was used as reducing agent and stabilizing polymer as well as
      electrospinning polymeric matrix for the fabrication of PVA/Ag-NP nanofibers.
      Afterwards, hydroxypropyl-beta-cyclodextrin (HPbetaCD) was used as an additional
      reducing and stabilizing agent in order to control size and uniform dispersion of
      Ag-NP. The size of Ag-NP was ~8 nm and some Ag-NP aggregates were observed for
      PVA/Ag-NP nanofibers, conversely, the size of Ag-NP decreased from ~8 nm down to
      ~2 nm within the fiber matrix without aggregation were attained for PVA/HPbetaCD
      nanofibers. The PVA/Ag-NP and PVA/HPbetaCD/Ag-NP nanofibers exhibited surface
      enhanced Raman scattering (SERS) effect. Moreover, antibacterial properties of
      PVA/Ag-NP and PVA/HPbetaCD/Ag-NP nanofibrous mats were tested against Gram
      negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria.

PMID- 24274574
TI  - Novel chitosan-ZnO based nanocomposites as luminescent tags for cellulosic
      materials.
AB  - Novel chitosan-ZnO composites have been synthesized as luminescent taggants for
      cellulosic materials. The synthesized chitosan-ZnO nanospheres (CS-ZnO NS),
      chitosan-ZnO-oleic acid quantum dots (CS-ZnO-oleic QD) and chitosan-ZnO-oleic
      acid:Eu(3+) doped nanorods (CS-ZnO-oleic:Eu(3+) NR) were characterized by X-ray
      diffraction, photoluminescence spectroscopy, FTIR spectroscopy and transmission
      electron microscopy. The prepared luminescent CS-ZnO composites were used in
      printing paste and applied to different types of papers and textiles by using
      screen printing technique. The colorimetric values of the printed CS-ZnO-oleic
      acid and CS-ZnO-oleic:Eu(3+) showed that printing caused slightly change in color
      values. Scanning electron microscopy images and color values of the printed
      surface showed that CS-ZnO-oleic QD and highly luminescence CS-ZnO-olic:Eu(3+) NR
      are suitable for use as a printed security feature. 

PMID- 24274575
TI  - Stimuli sensitive super-macroporous cryogels based on photo-crosslinked 2
      hydroxyethylcellulose and chitosan.
AB  - Original pH sensitive cryogels, based on two biodegradable natural polymers
      chitosan (CS) and 2-hydroxyethylcellulose (HEC), were obtained via cryogenic
      treatment of semi-dilute aqueous solutions and UV induced crosslinking in frozen
      state. H2O2 and N,N'-methylenebisacrylamide (BisAAm) were used as photoinitiator
      and crosslinking agent, respectively. BisAAm facilitated the formation of polymer
      co-network and increased both the gel fraction yield and mechanical strength of
      cryogels. The influence of chitosan content on the physico-mechanical properties
      of HEC-CS cryogels was investigated. In general, the increase of CS fraction in
      the polymer co-network increased the degree of swelling and enhanced
      significantly the storage modulus of materials. All HEC-CS cryogels obtained were
      opalescent sponge-like materials, which quickly release/uptake water due to their
      open porous structure. The incorporation of CS provided pH dependent swelling and
      good bioadhesive properties of cryogels. HEC-CS cryogels were further exploited
      as drug delivery systems of the highly water soluble drug metronidazole belonging
      to BCS Class l.

PMID- 24274576
TI  - Investigation of Cu2+ binding to human and rat amyloid fragments Abeta (1-16)
      with a protein nanopore.
AB  - Recent evidence shows that metal coordination by amyloid beta peptides (Abeta)
      determines structural alterations of peptides, and His-13 from Abeta is crucial
      for Cu(2+) binding. This study used the truncated, more soluble Abeta1-16
      isoforms derived from human and rat amyloid peptides to explore their interaction
      with Cu(2+) by employing the membrane-immobilized alpha-hemolysin (alpha-HL)
      protein as a nanoscopic probe in conjunction with single-molecule
      electrophysiology techniques. Unexpectedly, the experimental data suggest that
      unlike the case of the human Abeta1-16 peptide, Cu(2+) complexation by its rat
      counterpart leads to an augmented association and dissociation kinetics of the
      peptide reversible interaction with the protein pore, as compared to the Cu(2+)
      free peptide. Single-molecule electrophysiology data reveal that both human and
      rat Cu(2+)-complexed Abeta peptides induce a higher degree of current flow
      obstruction through the alpha-HL pore, as compared to the Cu(2+)-free peptides.
      It is suggested that morphology changes brought by Cu(2+) binding to such
      amyloidic fragments depend crucially upon the presence of the His-13 residue on
      the primary sequence of such peptide fragments, and the alpha-HL protein-based
      approach provides unique opportunities and challenges to probing metal-induced
      folding of peptides. 

PMID- 24274577
TI  - An optical sensing strategy leading to in situ monitoring of the degradation of
      mesoporous magnetic supraparticles in cells.
AB  - Mesoporous magnetic supraparticles (meso-MSPs) as multifunctional targeted drug
      carriers have attracted much attention, because of their easy magnetic-field
      manipulation and in situ sensing functionality. In this paper, a Fe(3+)-selective
      chemodosimeter fluorescent probe (FP-1) was synthesized and loaded inside of the
      meso-MSPs (meso-MSPs/probe); the meso-MSPs/probe nanocomposites were then used to
      monitor the degradation of meso-MSPs in cells. In our experiments, strong
      fluorescence intensity was observed in HeLa cells, because of their acidic
      intracellular environment, which can quickly degrade the meso-MSPs and then
      release Fe(3+) ions in cells that, in turn, activate the fluorescence of FP-1.
      Meanwhile, a very weak fluorescence signal was detected in HEK 293T cells due to
      the relative neutral intracellular environment of HEK 293T cells, which prevented
      the Fe(3+) ion from leaching out of meso-MSPs. Moreover, this degradation
      luminescence relationship of the meso-MSPs/probe nanocomposites not only assisted
      us to understand the degradation status of meso-MSPs in cells, but also allowed
      us to recognize the peculiarity of different cells with various intracellular
      environments. 

PMID- 24274578
TI  - Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses
      hepatocellular carcinoma metastasis through inhibiting Rac1.
AB  - BACKGROUND: Tumor invasion and metastasis are the major reasons for leading death
      of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules
      that can suppress invasion and metastasis of tumor will provide novel targets for
      HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2,
      is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice
      but its function in human is unclear. Our previous research has shown that TIPE2
      is downregulated in human primary HCC compared with the paired adjacent non-tumor
      tissues. RESULTS: In present study, we provide evidence that TIPE2 inhibits
      effectively human hepatocellular carcinoma metastasis. The forced expression of
      TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration
      and invasion in vitro and suppresses growth and metastasis of HCC in vivo.
      Clinical information from a cohort of 112 patients reveals that loss or reduced
      expression of TIPE2 in primary HCC tissues is significantly associated with tumor
      metastasis. Mechanically, TIPE2 inhibits the migration and invasion through
      targeting Rac1 and then reduces F-actin polymerization and expression of matrix
      metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA). CONCLUSION:
      Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by
      which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2
      will be a new target for HCC therapy.

PMID- 24274579
TI  - Kinetic analysis of [11C]befloxatone in the human brain, a selective radioligand
      to image monoamine oxidase A.
AB  - BACKGROUND: [11C]Befloxatone measures the density of the enzyme monoamine oxidase
      A (MAO-A) in the brain. MAO-A is responsible for the degradation of different
      neurotransmitters and is implicated in several neurologic and psychiatric
      illnesses. This study sought to estimate the distribution volume (VT) values of
      [11C]befloxatone in humans using an arterial input function. METHODS: Seven
      healthy volunteers were imaged with positron emission tomography (PET) after
      [11C]befloxatone injection. Kinetic analysis was performed using an arterial
      input function in association with compartmental modeling and with the Logan
      plot, multilinear analysis (MA1), and standard spectral analysis (SA) at both the
      regional and voxel level. Arterialized venous samples were drawn as an
      alternative and less invasive input function. RESULTS: An unconstrained two
      compartment model reliably quantified VT values in large brain regions. A
      constrained model did not significantly improve VT identifiability. Similar VT
      results were obtained using SA; however, the Logan plot and MA1 slightly
      underestimated VT values (about -10%). At the voxel level, SA showed a very small
      bias (+2%) compared to compartmental modeling, Logan severely underestimated VT
      values, and voxel-wise images obtained with MA1 were too noisy to be reliably
      quantified. Arterialized venous blood samples did not provide a satisfactory
      alternative input function as the Logan-VT regional values were not comparable to
      those obtained with arterial sampling in all subjects. CONCLUSIONS: Binding of
      [11C]befloxatone to MAO-A can be quantified using an arterial input function and
      a two-compartment model or, in parametric images, with SA.

PMID- 24274580
TI  - Validity of the Oral Behaviours Checklist: correlations between OBC scores and
      intensity of facial pain.
AB  - The first purpose of this study was to translate the Oral Behaviours Checklist
      (OBC) into Dutch and to examine its psychometric properties. The second purpose
      was to examine the correlations between scores on the OBC and facial pain, while
      controlling for the possible confounding effects of psychosocial factors, such as
      stress, depression, somatisation and anxiety. The OBC was translated, following
      the international RDC/TMD consortium guidelines. Its psychometric properties were
      examined by assessing the test-retest reliability and concurrent validity
      [correlations between the OBC and the previously developed Oral Parafunctions
      Questionnaire (OPQ)]. Participants were 155 patients with TMD (77% female; mean
      age and s.d. = 43.6 and 14.4 years). The translation of the OBC into Dutch
      proceeded satisfactorily. The psychometric properties of the Dutch OBC were good;
      test-retest reliability was excellent (ICC = 0.86, P < 0.001). Concurrent
      validity was good: the correlation between the OBC and OPQ was high (r = 0.757, P
      < 0.001), while the correlations between individual items ranged from 0.389 to
      0.892 (P < 0.001). Similar to previous Dutch studies using the OPQ, no
      significant correlation was found between oral parafunctions and facial pain (r =
      0.069, P = 0.892). No significant correlations could be found between oral
      parafunctional behaviours and facial pain.

PMID- 24274582
TI  - Leading multiple teams: average and relative external leadership influences on
      team empowerment and effectiveness.
AB  - External leaders continue to be an important source of influence even when teams
      are empowered, but it is not always clear how they do so. Extending research on
      structurally empowered teams, we recognize that teams' external leaders are often
      responsible for multiple teams. We adopt a multilevel approach to model external
      leader influences at both the team level and the external leader level of
      analysis. In doing so, we distinguish the influence of general external leader
      behaviors (i.e., average external leadership) from those that are directed
      differently toward the teams that they lead (i.e., relative external leadership).
      Analysis of data collected from 451 individuals, in 101 teams, reporting to 25
      external leaders, revealed that both relative and average external leadership
      related positively to team empowerment. In turn, team empowerment related
      positively to team performance and member job satisfaction. However, while the
      indirect effects were all positive, we found that relative external leadership
      was not directly related to team performance, and average external leadership
      evidenced a significant negative direct influence. Additionally, relative
      external leadership exhibited a significant direct positive influence on member
      job satisfaction as anticipated, whereas average external leadership did not.
      These findings attest to the value in distinguishing external leaders' behaviors
      that are exhibited consistently versus differentially across empowered teams.
      Implications and future directions for the study and management of external
      leaders overseeing multiple teams are discussed.

PMID- 24274581
TI  - Identification of the GPR55 antagonist binding site using a novel set of high
      potency GPR55 selective ligands.
AB  - GPR55 is a class A G protein-coupled receptor (GPCR) that has been implicated in
      inflammatory pain, neuropathic pain, metabolic disorder, bone development, and
      cancer. Initially deorphanized as a cannabinoid receptor, GPR55 has been shown to
      be activated by non-cannabinoid ligands such as l-alpha-lysophosphatidylinositol
      (LPI). While there is a growing body of evidence of physiological and
      pathophysiological roles for GPR55, the paucity of specific antagonists has
      limited its study. In collaboration with the Molecular Libraries Probe Production
      Centers Network initiative, we identified a series of GPR55 antagonists using a
      beta-arrestin, high-throughput, high-content screen of ~300000 compounds. This
      screen yielded novel, GPR55 antagonist chemotypes with IC50 values in the range
      of 0.16-2.72 MUM [Heynen-Genel, S., et al. (2010) Screening for Selective Ligands
      for GPR55: Antagonists (ML191, ML192, ML193) (Bookshelf ID NBK66153; PMID entry
      22091481)]. Importantly, many of the GPR55 antagonists were completely selective,
      with no agonism or antagonism against GPR35, CB1, or CB2 up to 20 MUM. Using a
      model of the GPR55 inactive state, we studied the binding of an antagonist series
      that emerged from this screen. These studies suggest that GPR55 antagonists
      possess a head region that occupies a horizontal binding pocket extending into
      the extracellular loop region, a central ligand portion that fits vertically in
      the receptor binding pocket and terminates with a pendant aromatic or
      heterocyclic ring that juts out. Both the region that extends extracellularly and
      the pendant ring are features associated with antagonism. Taken together, our
      results provide a set of design rules for the development of second-generation
      GPR55 selective antagonists.

PMID- 24274583
TI  - Antitumor activity of TNF-alpha after intratumoral injection using an in situ
      thermosensitive hydrogel.
AB  - Local drug delivery strategies based on nanoparticles, gels, polymeric films,
      rods and wafers are increasingly used in cancer chemotherapy in order to enhance
      therapeutic effect and reduce systemic toxicity. Herein, a biodegradable and
      biocompatible in situ thermosensitive hydrogel was designed and employed to
      deliver tumor necrosis factor-alpha (TNF-alpha) locally by intratumoral
      injection. The triblock copolymer was synthesized by ring-opening polymerization
      (ROP) of beta-butyrolactone (beta-BL) and lactide (LA) in bulk using polyethylene
      glycol (PEG) as an initiator and Sn(Oct)2 as the catalyst, the polymer was
      characterized by NMR, gel permeation chromatography and differential scanning
      calorimetry. Blood and tumor pharmacokinetics and in vivo antitumor activity of
      TNF-alpha after intratumoral administration in hydrogel or solution with the same
      dose were evaluated on S180 tumor-bearing mice. Compared with TNF-alpha solution,
      TNF-alpha hydrogel exhibited a longer T1/2 (4-fold) and higher AUCtumor (19
      fold), but Cmax was lower (0.5-fold), which means that the hydrogel formulation
      improved the efficacy with a lower systhemic exposure than the solution
      formation. In addition, TNF-alpha hydrogel improved the antitumor activity and
      survival due to lower systemic exposure than the solution. These results
      demonstrate that the in situ thermosensitive hydrogel-based local delivery system
      by intratumoral injection is well suited for the administration of TNF-alpha. 

PMID- 24274584
TI  - Trends in adiposity in Brazilian 7-10-year-old schoolchildren: evidence for
      increasing overweight but not obesity between 2002 and 2007.
AB  - BACKGROUND: The negative health consequences of childhood overweight/obesity
      (OW/OB) are well known. Therefore, an accurate monitoring of the OW/OB prevalence
      is essential. Anthropometry is the most practical and cost-effective method for
      nutritional status evaluation. AIM: To describe trends in the nutritional status
      among 7-10-year-old children by investigating changes in the prevalence of
      stunting, thinness, overweight, obesity, risk and excess abdominal adiposity, and
      to study changes in height-for-age, body mass index (BMI) and waist circumference
      (WC). SUBJECTS AND METHODS: A school-based sample of 7-10-year-old children
      participated in two cross-sectional studies in 2002 (n = 2936) and 2007 (n =
      1232) in Florianopolis, southern Brazil. Prevalence of stunting, risk and excess
      abdominal adiposity and changes in the distribution of height-for-age, BMI-for
      age, WC-for-age z-scores were evaluated. Three BMI-based references were used to
      define the prevalence of thinness, overweight and obesity. RESULTS: Between 2002
      2007, the prevalence of stunting, thinness, obesity and excess abdominal
      adiposity remained stable, whereas overweight (including obesity) increased 10
      23% in boys and 18-21% in girls, depending on the BMI reference used. The risk of
      abdominal adiposity increased in boys, but not in girls. No significant change
      was observed in mean height, BMI, WC-for-age z-scores. CONCLUSIONS: This study
      identified a potential levelling off in the prevalence of obesity and excess
      abdominal adiposity, but a continuing increase in the prevalence of overweight.

PMID- 24274585
TI  - Twenty-year summary of surveillance for human hantavirus infections, United
      States.
AB  - In the past 20 years of surveillance for hantavirus in humans in the United
      States, 624 cases of hantavirus pulmonary syndrome (HPS) have been reported, 96%
      of which occurred in states west of the Mississippi River. Most hantavirus
      infections are caused by Sin Nombre virus, but cases of HPS caused by Bayou,
      Black Creek Canal, Monongahela, and New York viruses have been reported, and
      cases of domestically acquired hemorrhagic fever and renal syndrome caused by
      Seoul virus have also occurred. Rarely, hantavirus infections result in mild
      illness that does not progress to HPS. Continued testing and surveillance of
      clinical cases in humans will improve our understanding of the etiologic agents
      involved and the spectrum of diseases. 

PMID- 24274586
TI  - Synthetic microbial ecosystems: an exciting tool to understand and apply
      microbial communities.
AB  - Many microbial ecologists have described the composition of microbial communities
      in a plenitude of environments, which has greatly improved our basic
      understanding of microorganisms and ecosystems. However, the factors and
      processes that influence the behaviour and functionality of an ecosystem largely
      remain black boxes when using conventional approaches. Therefore, synthetic
      microbial ecology has gained a lot of interest in the last few years. Because of
      their reduced complexity and increased controllability, synthetic communities are
      often preferred over complex communities to examine ecological theories. They
      limit the factors that influence the microbial community to a minimum, allowing
      their management and identifying specific community responses. However, besides
      their use for basic research, synthetic ecosystems also found their way towards
      different applications, like industrial fermentation and bioremediation. Here, we
      review why and how synthetic microbial communities are applied for research
      purposes and for which applications they have been and could be successfully
      used. 

PMID- 24274587
TI  - Preparation and characterization of microemulsion of cilostazol for enhancement
      of oral bioavailability.
AB  - Cilostazol is a promising drug for antiplatelet combination therapy that is very
      important for treatment for various cardiovascular disorders. However, oral
      delivery of this drug is greatly impeded by the poor solubility in aqueous
      solutions. The aim of this study was to develop microemulsion (ME) delivery
      system capable of improving the drug bioavailability. In this study, Capmul MCM
      C8 (glycerol monocaprylate) based MEs containing Tween 20(polysorbate 20) and/or
      Labrafil M 1944(poly oxyglycerides) as surfactant(S) and Transcutol P(diethyl
      glycol monoethyl ether) as cosurfactant(CoS) were studied as potential delivery
      systems of cilostazol. A number of such systems were prepared containing
      different S:CoS ratios(1:1, 2:1 and 3:1) based on phase diagrams. Loading of
      cilostazol was selected as per solubilization capacity and was characterized for
      pH, viscosity, conductivity, particle size, zeta potential and % transmittance.
      The MEs systems were further investigated for chemical stability, diffusion and
      bioavailability. Cilostazol displayed high solubility in microemulsions with
      particle size up to 70 nm. It was also stable at ambient temperature up to 6
      months without significant change in particle size, zeta potential, and %
      transmittance. Dilution up to 100 fold with aqueous medium observed a visible
      cloudiness having a particle size up to 104 nm. The in vitro release, and ex vivo
      intraduodenal diffusion, and in vivo study indicated the capacity of developed ME
      to improve the bioavailability (1.43 fold) via oral route administration when
      compared with commercially available tablets (Pletoz-50).

PMID- 24274588
TI  - Whole grain intake and survival among Scandinavian colorectal cancer patients.
AB  - To our knowledge, no studies of associations between intake of whole grain (WHG)
      and survival of colorectal cancer have been published, despite evidence that
      dietary fiber, and to some extent WHG, are associated with lower risk of
      colorectal cancer. Scandinavia is an area where the WHG consumption traditionally
      is high. We performed a case-only (N = 1119) study in the Scandinavian HELGA
      cohort of pre-diagnosis WHG intake (total WHG, WHG wheat, WHG rye, and WHG oats)
      and survival of colorectal cancer. Cox regression analyses were used to study the
      associations, both in categorical and continuous models, stratified by location
      (proximal, distal, rectum) and country. No evidence of an association was found,
      neither for total WHG intake (hazard ratio = 1.32, 95% confidence interval: 0.88
      1.97 lowest vs. highest tertile, adjusted for age at diagnosis, metastasis
      status, smoking, folate, margarine, and energy), nor for specific grains.
      Prediagnosis consumption of WHG does not seem to improve survival of colorectal
      cancer in subjects diagnosed within this prospective population-based
      Scandinavian cohort. 

PMID- 24274590
TI  - Reactivity differences of combined and free amino acids: quantifying the
      relationship between three-dimensional protein structure and singlet oxygen
      reaction rates.
AB  - It has long been appreciated that the photooxidation kinetics of amino acid (AA)
      residues in an intact protein differ from those of free AAs due to differences in
      the local steric microenvironment, such as its location in the three-dimensional
      structure. Yet there are only a few studies that have quantified the effect of
      protein structure on the photochemical reactivity of its residues. This is
      important for predicting phototransformation rates of AAs in aquatic environments
      where AAs in combined forms (e.g., oligopeptides and proteins) are more abundant
      than free AAs. In this work, the photochemical reactivity differences between
      free and combined AAs were assessed. Singlet oxygen ((1)O2) reaction kinetics of
      individual photooxidizable residues in the protein glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) were examined. The results suggest that the (1)O2
      accessibility of residues in intact GAPDH has a profound effect on their
      photodegradation kinetics and for histidine residues can explain most of the
      variation in (1)O2 reactivity. Additionally, (1)O2-accessibile surface area
      values of residues calculated from protein crystal structure data are useful in
      predicting their reaction rates in GAPDH. This work illustrates a new approach to
      assess the differential photochemical reactivity of AA-based biomolecules in
      natural environments or engineered applications. 

PMID- 24274591
TI  - Accelerated phase at initial presentation in Chediak-Higashi syndrome: is it
      really uncommon ?

PMID- 24274589
TI  - Transluminal endoscopic step-up approach versus minimally invasive surgical step
      up approach in patients with infected necrotising pancreatitis (TENSION trial):
      design and rationale of a randomised controlled multicenter trial
      [ISRCTN09186711].
AB  - BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease
      that nearly always requires intervention. Traditionally, primary open
      necrosectomy has been the treatment of choice. In recent years, the surgical step
      up approach, consisting of percutaneous catheter drainage followed, if necessary,
      by (minimally invasive) surgical necrosectomy has become the standard of care. A
      promising minimally invasive alternative is the endoscopic transluminal step-up
      approach. This approach consists of endoscopic transluminal drainage followed, if
      necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less
      invasive endoscopic step-up approach is superior to the surgical step-up approach
      in terms of clinical and economic outcomes. METHODS/DESIGN: The TENSION trial is
      a randomised controlled, parallel-group superiority multicenter trial. Patients
      with (suspected) infected necrotising pancreatitis with an indication for
      intervention and in whom both treatment modalities are deemed possible, will be
      randomised to either an endoscopic transluminal or a surgical step-up approach.
      During a 4 year study period, 98 patients will be enrolled from 24 hospitals of
      the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death
      and major complications within 6 months following randomisation. Secondary
      endpoints include complications such as pancreaticocutaneous fistula, exocrine or
      endocrine pancreatic insufficiency, need for additional radiological, endoscopic
      or surgical intervention, the need for necrosectomy after drainage, the number of
      (re-)interventions, quality of life, and total direct and indirect costs.
      DISCUSSION: The TENSION trial will answer the question whether an endoscopic step
      up approach reduces the combined primary endpoint of death and major
      complications, as well as hospital stay and related costs compared with a
      surgical step-up approach in patients with infected necrotising pancreatitis.

PMID- 24274592
TI  - Flat flow profiles achieved with microfluidics generated by redox
      magnetohydrodynamics.
AB  - Horizontal flow profiles having uniform velocities (3-13% RSD) at fixed heights
      across 0.5, 2.0, and 5.6 mm widths, with magnitudes of <=124 MUm/s, can be
      sustained along a ~25.0 mm path using redox-magnetohydrodynamics (MHD)
      microfluidic pumping in a small volume (14.3 mm wide * 27.0 mm long * 620 MUm
      high) on a chip. Uniform velocity profiles are important in moving volume
      elements without shape distortion for assays and separations for lab-on-a-chip
      applications. Fluid movement resulting from the MHD force (FB = j * B) was
      monitored with video microscopy by tracking 10 MUm, polystyrene latex beads mixed
      into the solution. The ionic current density, j, was generated in 0.095 M
      K3Fe(CN)6, 0.095 M K4Fe(CN)6, and 0.095 M KCl by applying a constant current
      across a 0.5, 2.0, or 5.6 mm gap between an anode-cathode pair of electrodes,
      consisting of one to four shorted parallel, coplanar gold microbands [each 25.0
      mm * 98 MUm * ~100 nm (thickness), and separated by 102 MUm] fabricated on an
      insulated silicon substrate. By shorting the increasing numbers of microbands
      together, increasing currents (118, 180, 246, and 307 MUA) could be applied
      without electrode damage, and the impact of ionic current density gradients on
      velocity profiles over the anodes and cathodes could also be investigated. The
      magnetic field, B, was produced with a 0.36 T NdFeB permanent magnet beneath the
      chip. Data analysis was performed using particle image velocimetry software. A
      vertical flow profile was also obtained in the middle of the 5.6 mm gap. 

PMID- 24274594
TI  - How stable 'should' epigenetic modifications be? Insights from adaptive
      plasticity and bet hedging.
AB  - Although there is keen interest in the potential adaptive value of epigenetic
      variation, it is unclear what conditions favor the stability of these variants
      either within or across generations. Because epigenetic modifications can be
      environmentally sensitive, existing theory on adaptive phenotypic plasticity
      provides relevant insights. Our consideration of this theory suggests that stable
      maintenance of environmentally induced epigenetic states over an organism's
      lifetime is most likely to be favored when the organism accurately responds to a
      single environmental change that subsequently remains constant, or when the
      environmental change cues an irreversible developmental transition. Stable
      transmission of adaptive epigenetic states from parents to offspring may be
      selectively favored when environments vary across generations and the parental
      environment predicts the offspring environment. The adaptive value of stability
      beyond a single generation of parent-offspring transmission likely depends on the
      costs of epigenetic resetting. Epigenetic stability both within and across
      generations will also depend on the degree and predictability of environmental
      variation, dispersal patterns, and the (epi)genetic architecture underlying
      phenotypic responses to environment. We also discuss conditions that favor
      stability of random epigenetic variants within the context of bet hedging. We
      conclude by proposing research directions to clarify the adaptive significance of
      epigenetic stability. 

PMID- 24274593
TI  - Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting
      microglial activation and downregulating ERK and p38 MAPK signaling in chronic
      cerebral hypoperfused rat.
AB  - BACKGROUND: The cardiotonic pill (CP) is a herbal medicine composed of Salvia
      miltiorrhiza (SM), Panax notoginseng (PN), and Dryobalanops aromatica Gaertner
      (DAG) that is widely used to treat cardiovascular diseases. The present
      experiment was conducted to examine the effects of CP on white matter and
      hippocampal damage induced by chronic cerebral hypoperfusion. METHODS: Chronic
      cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral
      common carotid artery occlusion (BCCAo). Daily oral administration of CP (200
      mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of
      microglial activation and myelin basic protein (MBP) were measured in the white
      matter and hippocampus of rats with chronic BCCAo, and the expression levels of
      mitogen-activated protein kinases (MAPKs) and inflammatory markers such as
      cyclooxygenase-2, interleukin-1beta, and interleukin-6 were examined. RESULTS:
      MBP expression was reduced in the white matter and hippocampal regions of rats
      that received BCCAo. In contrast, reduced levels of MBP were not observed in
      BCCAo rats given CP treatments. The administration of CP alleviated microglial
      activation, the alteration of ERK and p38 MAPK signaling, and inflammatory
      mediator expression in rats with chronic BCCAo. CONCLUSION: These results suggest
      that CP may have protective effects against chronic BCCAo-induced white matter
      and hippocampal damage by inhibiting inflammatory processes including microglial
      activation and proinflammatory mediator expression, and downreguating the
      hyperphosphorylation of ERK and p38 MAPK signaling.

PMID- 24274595
TI  - A prominent role for the IL1 pathway and IL15 in susceptibility to chronic
      cavitary pulmonary aspergillosis.
AB  - Chronic cavitary pulmonary aspergillosis (CCPA) is a progressive lung condition
      with a 10-30% annual mortality. Although overtly immunocompetent, some
      immunogenetic defect in patients is likely. To investigate a possible
      immunogenetic defect in CCPA, we analysed biologically plausible candidate genes
      in 112 CCPA patients and 279 healthy controls in a genetic association study of
      genes involved in the post-recognition immune response to Aspergillus fumigatus.
      We also compared gene expression in monocyte-derived macrophages from subjects
      with and without disease, both at baseline and during stimulation with A.
      fumigatus. Compared with macrophages from healthy subjects, CCPA macrophages
      showed unrestrained rises in IL1A, IL1B, IL6, IRAK2 and TRAF6 throughout the
      experiment, and a lack of expression of TGFB1 at 9 h. Single nucleotide
      polymorphisms (SNPs) associated with CCPA were found in IL1B (n = 2), IL1RN and
      IL15 (n = 3). Uncontrolled expression of IL1 and IL6 and continuing high levels
      of these cytokines may result in continuing cellular influx and pro-inflammatory
      responses, inhibiting disease resolution and contributing to disease progression
      in CCPA. The association of SNPs in IL1B, IL1RN and IL15 with CCPA supports a
      role for the IL1 pathway, as well as implicating the IL15 gene, in susceptibility
      to CCPA. 

PMID- 24274596
TI  - Time-series pattern of gene expression profile in gentamycin-induced
      nephrotoxicity.
AB  - There have been many studies investigating the genomic biomarker and/or molecular
      mechanism of nephrotoxicity using microarray. However, most of these researches
      were carried out by studying gene expression changes at one specific time point.
      As gene expression varies with time and disease stage, the current study
      investigated the time-series pattern of gene expression in a rat model using a
      typical nephrotoxic compound. Rats were administrated with 80 mg/kg gentamycin or
      saline by intramuscular injection for 14 consecutive days followed by a 28-d
      recovery. Rats were scarified on D2, D4, D8, D15 and Recovery Day (R29), when
      kidneys were obtained for whole-genome microarray analysis and histological
      examination. Urine was collected at each necropsy for kidney injury molecular-1
      (KIM-1) analysis. The KIM-1 detection and histological examination confirmed the
      nephrotoxicity. After differentially expression genes (DEGs) identification,
      there were 4360 and 4323 regulated genes for females and males, respectively.
      However, few overlapping expression genes co-regluated at each time point were
      found. By principle component analysis (PCA) and hierarchical cluster, the gene
      expression patterns were observed to be apparently associated with the disease
      stage. GO Annotation showed (1) immune response and related process, response to
      wounding, cell locomotion on D2; (2) cell death and apoptosis was also noted on
      D4; (3) processes of organic acid or carboxylic acid, apoptosis or cell death on
      D8 and D15; (4) processes of cell cycle, mitosis, division cell cycle on R29. In
      conclusion, the authors mapped the time-series gene expression patterns at the
      initiation, development and recovery stage of gentamycin-induced nephrotoxicity.

PMID- 24274597
TI  - Enhanced luminescence properties of InAs-InAsP core-shell nanowires.
AB  - Utilizing narrow band gap nanowire (NW) materials to extend nanophotonic
      applications to the mid-infrared spectral region (>2-3 MUm) is highly attractive,
      however, progress has been seriously hampered due to their poor radiative
      efficiencies arising from nonradiative surface and Auger recombination. Here, we
      demonstrate up to ~ 10(2) times enhancements of the emission intensities from
      InAs NWs by growing an InAsP shell to produce core-shell NWs. By systematically
      varying the thickness and phosphorus (P)-content of the InAsP shell, we
      demonstrate the ability to further tune the emission energy via large strain
      induced peak shifts that already exceed >100 meV at comparatively low fractional
      P-contents. Increasing the P-content is found to give rise to additional line
      width broadening due to asymmetric shell growth generated by a unique transition
      from {110}- to {112}-sidewall growth as confirmed by cross-sectional scanning
      transmission electron microscopy. The results also elucidate the detrimental
      effects of plastic strain relaxation on the emission characteristics,
      particularly in core-shell structures with very high P-content and shell
      thickness. Overall, our findings highlight that enhanced mid-infrared emission
      efficiencies with effective carrier confinement and suppression of nonradiative
      recombination are highly sensitive to the quality of the InAs-InAsP core-shell
      interface.

PMID- 24274598
TI  - An oxygen-chelate complex, palladium bis-acetylacetonate, induces apoptosis in
      H460 cells via endoplasmic reticulum stress pathway rather than interacting with
      DNA.
AB  - Current precious-metal-containing anticancer agents are mostly chelated with N
      containing ligands and function by interacting with DNA. In the present study,
      Pd(acac)2, a Pd(II) complex containing four O-donor ligands, has been evaluated
      as an active anticancer agent. Pd(acac)2 showed no interaction with N-ligand
      containing DNA and the S-ligand-containing DMSO, probably because of the two six
      member chelate rings that limit the release of the central Pd nuclei to bind to
      other ligands. Importantly, we found that Pd(acac)2 exhibited better growth
      inhibitory effects than cisplatin in several cancer cells. Treatment with
      Pd(acac)2 significantly induced apoptosis in H460 cells. Mechanistically,
      Pd(acac)2 induced the activation of a series of key components in ER stress
      mediated apoptotic pathway, followed by caspase cleavage and activation, while
      cisplatin showed no similar effects. CHOP knockdown by specific siRNA
      significantly attenuated Pd(acac)2-induced cell apoptosis. Finally, Pd(acac)2
      significantly inhibits H460 cell growth in xenograft mouse models. Taken
      together, these mechanistic insights on Pd(acac)2 provide us with a novel
      mechanism and strategy for the development of precious-metal-based anticancer
      drugs. 

PMID- 24274599
TI  - The RSSearchTM Registry: patterns of care and outcomes research on patients
      treated with stereotactic radiosurgery and stereotactic body radiotherapy.
AB  - BACKGROUND: The RSSearchTM Registry is a multi-institutional, observational,
      ongoing registry established to standardize data collection from patients treated
      with stereotactic radiosurgery (SRS) and/or stereotactic body radiotherapy
      (SBRT). This report describes the design, patient demographics, lesion
      characteristics, and SRS/SBRT treatment patterns in RSSearchTM. Illustrative
      patient-related outcomes are also presented for two common treatment sites--brain
      metastases and liver metastases. MATERIALS AND METHODS: Thirty-nine US centers
      participated in RSSearchTM. Patients screened for SRS/SBRT were eligible to be
      enrolled. Descriptive analyses were performed to assess patient characteristics,
      physician treatment practices, and clinical outcomes. Kaplan-Meier analysis was
      used to determine overall survival (OS), local progression-free (LPFS), and
      distant disease-free survival (DDFS). RESULTS: From January, 2008-January, 2013,
      11,457 patients were enrolled. The median age was 67 years (range 7-100 years);
      51% male and 49% female. Forty-six percent had no prior treatment, 22% had
      received chemotherapy, 19% radiation therapy and 17% surgery. There were 11,820
      lesions from 65 treatment locations; 54% extracranial and 46% intracranial. The
      most common treatment locations were brain/cranial nerve/spinal cord, lung,
      prostate and liver. Metastatic lesions accounted for the majority of cases
      (41.6%), followed by primary malignant (32.9%), benign (10.9%), recurrent (9.4%),
      and functional diseases (4.3%). SRS/SBRT was used with a curative intent in 39.8%
      and palliative care in 44.8% of cases. The median dose for all lesions was 30 Gy
      (range < 1-96.7 Gy) delivered in a median number of 3 fractions. The median dose
      for lesions in the brain/cranial nerve/spinal cord, lung, liver, pancreas and
      prostate was 24, 54, 45, 29 and 36.25 Gy, respectively. In a subset analysis of
      799 patients with 952 brain metastases, median OS was 8 months. For patients with
      a Karnofsky performance score (KPS) > 70, OS was 11 months vs. 4 months for KPS
      <= 70. Six-month and 12-month local control was 79% and 61%, respectively for
      patients with KPS <= 70, and 85% and 74%, respectively for patients with KPS >
      70. In a second subset analysis including 174 patients with 204 liver metastases,
      median OS was 22 months. At 1-year, LPFS and DDFS rates were 74% and 53%,
      respectively. LPFS CONCLUSION: This study demonstrates that collective patterns
      of care and outcomes research for SRS/SBRT can be performed and reported from
      data entered by users in a common database. The RSSearchTM dataset represents
      SRS/SBRT practices in a real world setting, providing a useful resource for
      expanding knowledge of SRS/SBRT treatment patterns and outcomes and generating
      robust hypotheses for randomized clinical studies.

PMID- 24274600
TI  - Hepatitis E virus variant in farmed mink, Denmark.
AB  - Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal
      reservoir. To investigate whether HEV occurs in mink in Denmark, we screened
      feces and tissues from domestic and wild mink. Our finding of a novel HEV variant
      supports previous findings of HEV variants in a variety of species. 

PMID- 24274601
TI  - Facile preparation of paclitaxel loaded silk fibroin nanoparticles for enhanced
      antitumor efficacy by locoregional drug delivery.
AB  - Non-toxic, safe materials and preparation methods are among the most important
      factors when designing nanoparticles (NPs) for future clinical application. Here
      we report a novel and facile method encapsulating anticancer drug paclitaxel
      (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer,
      without adding any toxic organic solvents, surfactants or other toxic agents. The
      paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130
      nm were formed in an aqueous solution at room temperature by self-assembling of
      SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular
      uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two
      human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity
      studies demonstrated that PTX kept its pharmacological activity when
      incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in
      vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice
      exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated
      superior antitumor efficacy by delaying tumor growth and reducing tumor weights
      compared with systemic administration. Furthermore, the organs of mice in NP
      treated groups didn't show obvious toxicity, indicating the in vivo safety of SF
      NPs. These results suggest that SF NPs are promising drug delivery carriers, and
      locoregional delivery of SF NPs could be a potential future clinical cancer
      treatment regimen. 

PMID- 24274602
TI  - [Identification of house dust mite fauna from allergic patients' mattress in six
      Mexican states].
AB  - BACKGROUND: House dust is considered an important source of aeroallergens, and
      the mites living there, are the main cause of allergy to it. In Mexico, there
      have been few about house dust fauna, and mostly limited to Mexico City.
      OBJECTIVE: To describe the house dust fauna from mattresses of allergic patients
      from different cities in Mexico. METHODS: Sixty dust samples were collected from
      mattresses in 6 Mexican states: Oaxaca, Tamaulipas, Veracruz, Puebla, Chiapas and
      Campeche. Mites were isolated under a stereomicroscope using lactic acid -0.9%
      NaCI solution. Identification was performed on fixed slides prepared with Hoyer
      solution. Skin Tests were already performed with allergen extracts of different
      house dust mites species in the 60 mattress' owners, whom had previously been
      diagnosed with respiratory allergy. RESULTS: The Pyroglyphidae family was found
      in 100% of dust samples. Dermatophagoides pteronyssinus (Dp) and Dermatophagoides
      farinae (Df) were the species most frequently found (>90%). These findings were
      in agreement with the skin tests results, where 100% of patients were positive to
      Dp, whereas 70% was positive to Df. It was evidenced for the first time the
      presence of Blomia tropicalis in Tamaulipas, Veracruz and Campeche states, and
      Dermatophagoides siboney in Campeche. Both species are important allergenic
      sources in tropical/subtropical climates. CONCLUSIONS: These results confirm the
      importance of Pyroglyphid house dust mites, as indoor sensitizers in different
      climatic and geographical regions in Mexico, as well as, the relevance of
      tropical species, particularly Blomia tropicalis and D. Siboney, in certain
      areas.

PMID- 24274603
TI  - [Standardizaron of the biological potency of allergenic extracts from
      Dermatophagoides pteronyssinus for immunotherapy].
AB  - BACKGROUND: Allergic rhinitis and asthma are the more frequent allergic diseases.
      Dermatophagoides pteronyssinus is one of the more clinically relevant causes of
      allergic diseases. OBJECTIVE: To standardize the biological potency Allergenic
      Bioequivalent Units (BAU) of Dermatophagoides pteronyssinus allergen extracts of
      three national laboratories. METHODS: This experimental, prospective,
      transversal, quantitative study included patients allergic to house dust mites.
      According to the FDA protocol, allergenic extracts of Dermatophagoides
      pteronyssinus from three Mexican manufacturers, were injected intradermally in
      threefold dilutions, until get an midpoint orthogonal diameters 50 mm erythema
      sum. Statistical analysis was done using logistic regression, one-way analysis of
      variance and Bonferroni test. RESULTS: We included 20 adult patients, 11 women
      and 9 men, aged between 16 and 45 years. Four patients had allergic asthma and
      rhinitis and 16 only had allergic rhinitis. There were no systemic anaphylactic
      reactions. Correlation coefficients of linear regression of the dose/response
      were to Allerstand r=0.55, Allergomex r=0.54 and Allerquim r=0.57(p=0.001).
      Dilutions calculated for 100,000 BAU/ml for each extract were Allerstand 1:26295,
      Allergomex 1:26341 and Allerquim 1:73993. The protein concentration (mcg/mL) was:
      Allergomex: 63, Allerquim 65, Allerstand 154. CONCLUSIONS: It was established the
      biological potency for each tested extract. We have found significant differences
      in the biological equivalence among the extracts from the three manufacturers.
      The procedure showed an adequate safety profile.

PMID- 24274604
TI  - [Risk factors for allergy to honey-bee venom in Mexican beekeepers].
AB  - BACKGROUND: Allergy to Hymenoptera venom has a low prevalence in the general
      population, but in beekeepers could be as high as 42%. The exposure to bee sting
      confers an occupational allergic risk to beekeepers, causing them sensitization
      during the first years, which if continues for a long time may induce immune
      tolerance. OBJECTIVE: To know some risk factors of allergic reactions to honey
      bee stings in a sample of beekeepers through a self-applied questionnaire.
      METHODS: A self-applied questionnaire was performed by beekeepers from the whole
      country, with questions about age, sex, time of beekeeping activities, average
      number of stings per month and types of post-sting reactions. The relative risk
      and the odds ratio were calculated for some risk factors. RESULTS: A total of
      1541 questionnaires were completed. The average age was 37 years. There were 1289
      (84%) men and 252 women. The average time of exposure to honey-bee sting was 7.2
      years, and the number of stings per month averaged 33. There was atopic family
      history in 14.5% of the beekeepers, and 20% of them had personal atopy. In 125
      (8%) beekeepers there were local allergic reactions and in 32 (2%) there were
      systemic allergic reactions. The relative risk for allergy to honey-bee venom in
      whom had atopic family history was 3.9 (CI 1.7-9.2), in those with less than 4
      stings per month was 3.2 (CI 1.12-9.33), in those with more than 20 years
      exposure was 0.97 (CI 0.95-0.98) and for those over 50 years of age was 0.32 (CI
      0.1-0.8). Beekeepers with less than 10 years of exposure had OR of 4.33 (CI 0.5
      33.9). CONCLUSIONS: The risk factors observed for hypersentivity to honey-bee
      venom in beekeepers were: atopic family history, less than 10 years of exposure
      and less than 4 stings per month. As probable protective factors we found the
      exposure for over 20 years and persons older than 50 years of age.

PMID- 24274605
TI  - [Cutaneous reactivity to common ivy (Hedera helix) pollen extract in allergic
      patients].
AB  - BACKGROUND: Common ivy is an ubiquitous ornamental plant found indoors and
      outdoors. It may cause occupational contact dermatitis and asthma. Many
      traditional and naturistic preparations may contain their extracts, hence
      sensitization may occur by several routes. OBJECTIVE: To determine the prevalence
      of sensitization to Hedera helix pollen by skin prick test on allergic subjects.
      METHODS: Skin prick tests (SPT) with 24 pollen extracts, including Hedera helix
      extract, were performed on 62 patients with allergic rhinitis, asthma, allergic
      conjunctivitis and atopic dermatitis. It was determined the frequency of
      sensitization to pollen extracts and the differences in the reactivity patterns
      among patients who showed a positive or negative result with Hedera helix
      extract. A cluster analysis was made to identify cross-allergenicity among pollen
      extracts. RESULTS: Eleven out of 62(17.7%) patients had a positive SPT with
      common ivy pollen extract. The main differences found were the number of pollen
      species to which patients were allergic. Patients with atopic dermatitis had a
      nine-fold higher frequency of positive skin tests with Hedera extracts, than
      subjects with other allergic diseases. CONCLUSIONS: Hedera helix pollen extract
      is a frequent cause of sensitization among allergic patients, and show cross
      allergenicity with pollen from different sources. There is a higher frequency of
      positive skin tests with Hedera extract in patients with atopic dermatitis than
      with other allergies.

PMID- 24274606
TI  - [Vitamin D deficiency in patients with common variable immunodeficiency, with
      autoimmune diseases and bronchiectasis].
AB  - BACKGROUND: Vitamin D regulates cellular activity, also it has effects on: innate
      and adaptive immunity, antimicrobial, anti-inflammatory and immunomodulatory
      functions. It has been suggested a possible association between vitamin D
      deficiency and increased risk and length of respiratory infections in patients
      with common variable immunodeficiency (CVID). METHODS: We conducted a descriptive
      study in patients with CVID. Vitamin D serum levels were measured in all
      patients. The results were analyzed using descriptive statistics by calculating
      measures of dispersion and central tendency. RESULTS: We studied 20 patients, 13
      women and 7 males, with an age average of 37 +/- 13.43 years. The mean
      concentration of vitamin D in patients was 15.43 ng/mL +/- 7.23. Thirty percent
      of all patients had severe Vitamin D deficiency, 45% had mild to moderate
      deficiency and 25% had insufficiency. Autoimmune diseases were associated in 35%
      of CVID patients, 42.8% of them had severe vitamin D deficiency. In patients with
      bronchiectasis, 85% were found with vitamin D deficiency, and it was severe in
      35.2%. 41% of patients with bronchiectasis were classified as severe on the
      Bhalla score of severity, 57% of these patients had severe deficiency and 14.2%
      mild-moderate deficiency. CONCLUSIONS: : We found deficiency of vitamin D in
      patients with CVID patients. Most of patients with CVID and bronchiectasis were
      detected with mild to severe vitamin D deficiency. Almost the half of patients
      with autoimmune diseases associated to CVID showed deficiency of vitamin D. We
      recommend to investigate the association of vitamin D deficiency on patients with
      immunodeficiencies.

PMID- 24274607
TI  - [Association between obesity and asthma severity in children].
AB  - BACKGROUND: The association of prevalence of obesity and asthma has increased
      significantly, this phenomenon seems multifactorial. Obesity is considered a risk
      factor for asthma. It has been reported positive association between obesity and
      allergic asthma. In Mexico there is no conclusive data about this issue. METHODS:
      The study was conducted in patients from 4 to 14 years of age, with allergic
      asthma. A history and physical examination and BMI estimation were performed, as
      well as the classification of asthma severity. RESULTS: We included 244 patients
      diagnosed with childhood allergic asthma, Fifty two patients (21.31%, OR 3.6)
      showed some degree of obesity (above the 85 percentile), 15.1% were male and 6%
      were female. Morbid obesity was found in 40 patients (16.3%). CONCLUSIONS: Our
      study found an increased prevalence of obesity in children with asthma, with a
      predominance in male gender, and showed a high association between the severity
      of asthma and increased BMI.

PMID- 24274608
TI  - [Quality of life in adults with variable common immunodeficiency and
      bronchiectasis].
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is a primary immunodeficiency
      characterized by hypogammaglobulinemia. Its prevalence is 1:10000 to 1:50000 with
      the highest incidence in children, 6 to 10 years, and in adults around age 29.
      The association of CVID and bronchiectasis has a prevalence of 17-90%. The
      quality of life in these patients can be assessed through instruments such as the
      Saint George Respiratory Questionnaire (SGRQ), which is designed for patients
      with chronic lung diseases and validated for the Mexican population. OBJECTIVE:
      [corrected] To evaluate the quality of life in adult patients with CVID and
      bronchiectasis using the SGRQ. METHODS: We applied CRSG to all the patients of
      the Immunodeficiencies Clinic from Hospital Especialidades CMN SXXI diagnosed
      with CVID and bronchiectasis for assessing quality of life which was evaluated in
      the three areas of application 1)Symptoms, 2)Activities and 3)Impact and the
      overall quality of life. We also analyzed its relationship with the severity of
      bronchiectasis confirmed by HRCT. RESULTS: 19 patients were included, (5 males,
      14 women) in whom it was found affected the overall quality of life in 84.2%.
      Women showed higher scores for all areas of the SGRQ (? 28.3 +/- 25.18 vs. ? 9.89
      +/- 8.14). The most affected area by both sexes was the Symptoms in 92% of women
      and 80% men. About the severity of bronchiectasis patients with mild
      bronquietasias presented scores 0-22.2 (x= 11.1 +/- 15.6), those with moderate
      bronchiectasis 3.24-56.9 (x=25.5 +/- 21.76) and severe with scores of 0-74.8 (x=
      24.1 +/- 28.5.). CONCLUSIONS: Patients with CVID and bronchiectasis have impaired
      quality of life, mainly associated with respiratory symptoms, with less
      involvement of and impact areas. Females were most affected in intensity to show
      higher scores.

PMID- 24274609
TI  - [Profilins: allergens with clinical relevance].
AB  - INTRODUCTION: Profilins are small ubiquitous proteins of 12-19 kDa involved in
      actin dynamics. These proteins are found in all eukaryotic organisms studied to
      date. Profilins have aminoacid sequences and tridimensional structure highly
      conserved. Allergy patients to pollen frequently have symptoms of allergy when
      ingestion of plant-derived foods like fruits, vegetables, seeds, among others.
      This phenomenon is known as latex-pollen-fruit allergy and it's the main cause of
      oral allergy syndrome (OAS) which is attributed to the cross-reactivity.
      Allergens shared between different sources theses are called panallergens for
      example are profilins which representing at least 20% of all pollen allergic
      patients. This cross-reactivity is results from the high amino acid sequence
      identity of profilin from plants, which is between 70% and 85%, this may explain
      the exacerbation symptoms of allergic patients to profilins from plants.
      OBJECTIVE: We described some characteristics which show us the important
      participation of the profilins in the sensitization of people allergic,
      especially to plants, fruits and pollen. METHODS: We looked research aminoacid
      sequences of all allergenic profilins reported to date and these were analyzed.
      CONCLUSIONS: Profilins are important allergens that are underrated in clinical
      practice and contribute to cross-reactivity in sensitized individuals by
      profilins from other sources.

PMID- 24274610
TI  - Isothermal DNA amplification coupled to Au-nanoprobes for detection of mutations
      associated to Rifampicin resistance in Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis accounted for 8.7 million new cases in 2011 and
      continues to be one of the leading human infectious diseases. Burdensome is the
      increasing rate of multi-drug resistant tuberculosis (MDRTB) and the difficulties
      created for treatment and public health control programs, especially in
      developing countries. Resistance to rifampicin (RIF), a first line antibiotic, is
      commonly associated with point mutations within the rpoB gene of Mycobacterium
      tuberculosis (Mtb) whose detection is considered the best early molecular
      predictor for MDRTB. Gold nanoparticles functionalized with thiol-modified
      oligonucleotides (Au-nanoprobes) have shown the potential to provide a rapid and
      sensitive detection method for Mtb and single base alterations associated with
      antibiotic resistance, namely in rpoB gene associated to RIF resistance. RESULTS:
      We developed a strategy based on the isothermal amplification of sample DNA
      (LAMP) coupled to specific Au-nanoprobes capable of identifying members of the
      Mtb complex (MTBC) and discriminating specific mutations within the rpoB gene.
      Integration of LAMP and Au-nanoprobe assay allowed to detect MTBC member and
      identify mutations linked to RIF resistance. A total of 12 biological samples
      were tested and a 100% specificity and sensitivity was attained. CONCLUSIONS:
      There is an increasing demand for simple, fast and cheap methods for the
      molecular identification of Mtb and for the detection of molecular tags
      associated to drug resistance suitable for use at point-of-need. Here we describe
      such a method, that as the potential to get molecular diagnostic of tuberculosis
      to remote environments.

PMID- 24274611
TI  - The aqueous cream controversy.

PMID- 24274612
TI  - Emerging antiangiogenics for renal cancer.
AB  - INTRODUCTION: Antiangiogenic therapy is considered to be the backbone of
      treatment strategy in metastatic renal cell carcinoma (mRCC). New, more focused,
      targeted drugs are emerging, while other targeted drugs oriented toward
      resistance or alternative mechanisms are under development. AREAS COVERED:
      Antiangiogenic agents include two types of agents: the monoclonal antibody,
      targeting vascular endothelial growth factor (VEGF), bevacizumab and the tyrosine
      kinase inhibitors (TKIs). Data regarding efficacy and safety of these agents are
      reported. Differences between the first generation of TKIs, sunitinib, sorafenib,
      and the new generation, pazopanib, axitinib and tivozanib are also detailed. Most
      of these agents have been approved in the treatment of kidney cancer in specific
      settings of the disease. EXPERT OPINION: The class of antiangiogenic drugs for
      treatment of mRCC is already relatively full. After 'me-too' drugs, more targeted
      drugs against VEGFR have been developed but have to demonstrate a benefit in
      first-line treatment. Another option for the development is to combine a known
      drug with an antiangiogenic inhibition profile and at least one additional target
      involved in resistance to an antiangiogenic or in an alternative pathway. The
      cost of approach with targeted drugs, including antiangiogenics, has led to a
      tremendous increase in the cost of care in mRCC.

PMID- 24274613
TI  - Emerging drugs for the treatment of uveitis.
AB  - INTRODUCTION: Uveitis is a potentially visually debilitating disease when
      untreated or poorly controlled. Chronic intermediate, posterior, or panuveitis
      often requires systemic immunosuppressive therapy to prevent such visual loss.
      AREAS COVERED: This review discusses existing treatments for ocular inflammation
      including corticosteroids, antimetabolites, alkylating agents, T-cell inhibitors,
      and biologic agents. Potential drugs being studied in clinical trials are
      introducing new routes for local corticosteroid delivery, and novel
      immunomodulators are exploring new targets of the inflammatory cascade. EXPERT
      OPINION: Treatment options for uveitis have expanded from even a decade ago.
      However, more clinical trials and research are needed to further our
      understanding of the mechanisms of ocular inflammation and the safety and
      efficacy of novel therapies.

PMID- 24274614
TI  - Emerging topical treatments for psoriasis.
AB  - INTRODUCTION: Psoriasis is an immune-mediated chronic inflammatory skin disease
      which classically presents as erythematous, scaly plaques affecting extensor
      surfaces of the limbs, scalp and trunk. Approximately 80% of patients have a mild
      to-moderate form routinely treated with topical medications, whereas
      phototherapy, systemic and biological therapies are typically reserved for
      treatment of moderate-to-severe psoriasis. AREAS COVERED: The major advances in
      psoriasis therapy in the past 15 years have been in new immunomodulatory and
      biological molecules, with a significant unmet need to have new, efficient and
      safe topical treatment options for the large percentage of patients for whom
      systemic therapy is not indicated. The available topical therapies
      (corticosteroids and vitamin D3 analogs) have remained relatively unchanged over
      the past several decades. This article reviews emerging topical drugs and
      formulations currently under evaluation in clinical trials. EXPERT OPINION: The
      time is right for a revolution in our topical therapy armamentarium. It has
      lagged significantly behind the systemic biological evolution of new drug
      development. Our large psoriasis population with mild-to-moderate psoriasis
      certainly deserves potent but safe and innovative topical agents with a new mode
      of action as well as with long-lasting clinical efficacy.

PMID- 24274615
TI  - Emerging drugs for prostate cancer.
AB  - INTRODUCTION: Androgen deprivation therapy is the mainstay treatment for patients
      with prostate cancer who are not candidates for definitive treatment, are
      diagnosed with advanced disease on initial presentation or progress after primary
      treatment. Patients who stop responding to androgen deprivation therapy develop
      castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical
      evaluation and drugs that have recently received FDA approval for the treatment
      of CRPC are reviewed. AREAS COVERED: As the natural history and signaling
      pathways of prostate cancer are better understood, new treatments and targeted
      therapies will be developed. The FDA recently approved 5 medications that
      increase survival in patients with CRPC. Additional medications and drug classes
      are being explored that may eventually lead to new treatment options. Articles
      were identified using a PubMed database search. EXPERT OPINION: Recent FDA
      medication approvals and the development of emerging treatments are promising for
      the future of patients with prostate cancer. The addition of new medications
      challenges physicians to identify the optimal sequence and/or combination in
      which newer and older medications should be administered. Physicians treating
      patients with prostate cancer have a growing responsibility to keep pace with
      these new medications so that they may counsel and treat patients appropriately.

PMID- 24274617
TI  - Predicting ease of perinephric fat dissection at time of open partial nephrectomy
      using preoperative fat density characteristics.
AB  - OBJECTIVE: To predict the ease of perinephric fat surgical dissection at the time
      of open partial nephrectomy (OPN) using perinepheric fat density characteristics
      as measured on preoperative computed tomography (CT). PATIENTS AND METHODS: In
      all, 41 consecutive OPN patients with available preoperative imaging and
      prospectively collected dissection difficulty assessment were identified. Using a
      scoring system that was adopted for the purposes of this study, the genitourinary
      surgeon quantified the difficulty of the perinephric fat dissection on the
      surface of the renal capsule at the time of surgery. On axial CT slice centred on
      the renal hilum, we measured the quantity and density of perinephric fat whose
      absorption coefficient was between -190 to -30 Hounsfield units. Correlation
      between perinephric fat surface density (PnFSD) as noted on preoperative imaging
      and as observed by the surgeon at time of surgery were correlated in a completely
      'double-blinded' fashion. Density comparisons between fat dissection difficulties
      were made using an anova. Associations between covariates and perinephric fat
      density were evaluated by univariate and multivariate logistic regression
      analyses. Receiver-operating characteristic (ROC) curves for six different
      predictive models were created to visualise the predictive enhancement of PnFSD.
      RESULTS: PnFSD was positively correlated with total surgical duration (Pearson's
      correlation coefficient 0.314, P = 0.04). PnFSD significantly correlated with
      gender (P = 0.001) and difficulty of perinephric fat surgical dissection (P <
      0.001) scores. The mean (sd) PnFSD for a dissection that was not difficult (n =
      19) was 5598.32 (1367.77) surface density pixel unit (SDPU), and for a difficult
      dissection (n = 22) was 10272.23 (3804.67) SDPU. Univariate analysis showed
      gender (P = 0.002), and PnFSD were predictive of the presence of 'sticky'
      perinephric fat. A multivariate analysis model showed that PnFSD was the only
      variable that remained an independent predictor of perinephric fat dissection
      difficulty (P = 0.01). Of the six ROC models assessed, only PnFSD had a
      significant capability to predict the difficulty of the perinephric fat
      dissection due to the presence of highly adherent 'sticky' fat, with an area
      under the curve of 0.87 (P < 0.001). CONCLUSION: Accurate preoperative assessment
      of perinephric fat density constitutes a strong indicator of perioperative fat
      dissection difficulty. Perinephric fat densities can be practically obtained from
      preoperative CT to identify 'sticky' fat, which may help determine the
      anticipated ease of surgical dissection, which can guide education, preoperative
      surgical planning, and potentially the surgical approach offered to patients.

PMID- 24274618
TI  - Immune responses to stress after stress management training in patients with
      rheumatoid arthritis.
AB  - INTRODUCTION: Psychological stress may alter immune function by activating
      physiological stress pathways. Building on our previous study, in which we report
      that stress management training led to an altered self-reported and cortisol
      response to psychological stress in patients with rheumatoid arthritis (RA), we
      explored the effects of this stress management intervention on the immune
      response to a psychological stress task in patients with RA. METHODS: In this
      study, 74 patients with RA, who were randomly assigned to either a control group
      or a group that received short stress management training, performed the Trier
      Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow
      up. Stress-induced changes in levels of key cytokines involved in stress and
      inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.
      RESULTS: Basal and stress-induced cytokine levels were not significantly
      different in patients in the intervention and control groups one week after
      treatment, but stress-induced IL-8 levels were lower in patients in the
      intervention group than in the control group at the follow-up assessment.
      CONCLUSIONS: In line with our previous findings of lower stress-induced cortisol
      levels at the follow-up of stress management intervention, this is the first
      study to show that relatively short stress management training might also alter
      stress-induced IL-8 levels in patients with RA. These results might help to
      determine the role of immunological mediators in stress and disease. TRIAL
      REGISTRATION: The Netherlands National Trial Register (NTR1193)

PMID- 24274619
TI  - Conformers of cysteine and cysteine sulfenic acid and mechanisms of the reaction
      of cysteine sulfenic acid with 5,5-dimethyl-1,3-cyclohexanedione (dimedone).
AB  - Equilibrium and molecular structures, relative energies of conformers of gaseous
      cysteine (Cys, C, Cys-SH) and gaseous cysteine sulfenic acid (Cys-SOH), and the
      mechanisms of the reaction of Cys-SOH with 3-hydroxy-5,5-dimethyl-2-cyclohexen-1
      one, the enol tautomer of 5,5-dimethyl-1,3-cyclohexadione (dimedone), have been
      studied using BD(T), CCSD(T), and QCISD(T) with the cc-pVTZ basis set and using
      MP2 and the density functionals B3LYP, B3PW91, PBE1PBE, PBEh1PBE, M062X, CAM
      B3LYP, and WB97XD with the 6-311+G(d,p) basis set. The structures of the six
      lowest energy conformers of gaseous Cys-SOH are compared with the six lowest
      energy conformers of gaseous cysteine (Cys-SH). The relative stability of the six
      lowest energy conformers of Cys-SH and Cys-SOH are influenced by the interplay
      among many factors including dispersive effects, electronic effects,
      electrostatic interactions, hydrogen bonds, inductive effects, and noncovalent
      interactions. The mechanism of the addition of the lowest energy conformer of
      cysteine sulfenic acid (Cys-SOH) to dimedone may proceed through a six-membered
      ring transition state structure and through cyclic hydrogen-bonded transition
      state structures with one water molecule (8-membered ring), with two water
      molecules (10-membered ring), and with three water molecules (12-membered ring).
      Inclusion of one and two water molecules in the transition state structures
      lowers the activation barrier, whereas inclusion of a third water molecule raises
      the activation barrier. 

PMID- 24274620
TI  - Collagen fibril orientation and tear strength across ovine skins.
AB  - Variability of physical properties across hides and skins requires careful
      consideration when manufacturing goods from leather. Therefore, an understanding
      of the extent of this variation and its nanostructural basis is useful. Tear
      strength tests were performed on ovine leather from a grid of 81 positions on
      skins. Synchrotron small-angle X-ray scattering measurements were made from three
      positions on the skin, from 26 skins. The X-ray structural measurements are
      compared with tear strengths of the samples. It is found that the thickness
      normalized tear strength does not vary greatly between different positions on the
      skin, in contrast to bovine hides. There is more variation between different
      skins than within the same skin. The collagen fibril orientation and orientation
      index, which has previously been shown to be correlated with tear strength, do
      not vary significantly between the different sampling positions in ovine skins.
      The collagen fibril orientation varies through the thickness of the skin in a
      consistent way. The consistency of collagen orientation in ovine leather between
      different positions on the skin is in marked contrast to bovine hides and informs
      the use of ovine leather for manufacturing applications. 

PMID- 24274621
TI  - Myelin structures formed by thermotropic smectic liquid crystals.
AB  - We report on transient structures, formed by thermotropic smectic-A liquid
      crystals, resembling the myelin figures of lyotropic lamellar liquid crystals.
      The thermotropic myelin structures form during the solubilization of a smectic-A
      droplet in an aqueous phase containing a cationic surfactant at concentrations
      above the critical micelle concentration. Similar to the lyotropic myelin
      figures, the thermotropic myelins appear in an optical microscope as flexible
      tubelike structures growing at the smectic/aqueous interface. Polarizing
      microscopy and confocal fluorescence microscopy show that the smectic layers are
      parallel to the tube surface and form a cylindrically bent arrangement around a
      central line defect in the tube. We study the growth behavior of this new type of
      myelins and discuss similarities to and differences from the classical lyotropic
      myelin figures. 

PMID- 24274622
TI  - Spontaneous generation of infectious prion disease in transgenic mice.
AB  - We generated transgenic mice expressing bovine cellular prion protein (PrP(C))
      with a leucine substitution at codon 113 (113L). This protein is homologous to
      human protein with mutation 102L, and its genetic link with Gerstmann-Straussler
      Scheinker syndrome has been established. This mutation in bovine PrP(C) causes a
      fully penetrant, lethal, spongiform encephalopathy. This genetic disease was
      transmitted by intracerebral inoculation of brain homogenate from ill mice
      expressing mutant bovine PrP to mice expressing wild-type bovine PrP, which
      indicated de novo generation of infectious prions. Our findings demonstrate that
      a single amino acid change in the PrP(C) sequence can induce spontaneous
      generation of an infectious prion disease that differs from all others identified
      in hosts expressing the same PrP(C) sequence. These observations support the view
      that a variety of infectious prion strains might spontaneously emerge in hosts
      displaying random genetic PrP(C) mutations. 

PMID- 24274623
TI  - Assessing head and trunk symmetry during sleep using tri-axial accelerometers.
AB  - Using two types of small, lightweight tri-axial accelerometers, we obtained
      evidence for the effectiveness of an approach for assessing head-trunk
      symmetrical or asymmetrical positions during sleep. First, we assessed the
      accuracy of our monitoring system in five healthy young adults (age range, 22-24
      years). The participants wore acceleration monitors on the sternum and forehead;
      then spent 5 min in six different positions. Once accuracy was confirmed, we
      assessed head-trunk symmetry during night-time sleep in 10 healthy children (age
      range, 3-13 years) and 10 young adults (age range, 21-26 years) in their home
      environments. All participants wore the monitors during one night's sleep in
      their homes. After computing head-trunk positions using the orientation data
      obtained by the accelerometers, head and trunk symmetry were evaluated. The head
      and trunk positions were correctly detected: the positional data from the trunk
      had 99% agreement, and the data from the head had 96% agreement. Both the young
      adults and children were observed to spend time with the head-trunk in asymmetric
      positions; however, the subjects changed position frequently so the asymmetrical
      postures were mobile. We concluded that the proposed monitoring system is a
      reliable and valid approach for assessing head-trunk symmetry during sleep at
      home. Implications for Rehabilitation We propose a head and trunk symmetry
      monitoring system using accelerometers. The proposed system could accurately
      identify head and trunk position. Asymmetrical positioning was seen in healthy
      participants but it was not immobile.

PMID- 24274624
TI  - Physical activity for people with dementia: a scoping study.
AB  - BACKGROUND: This scoping study aimed to identify how physical activity may
      benefit people with dementia; how and/or if current service provide these
      benefits; and what support they need to do so. METHODS: Methods included an
      evidence review using literature; mapping current service provision through a
      survey; and in-depth interviews with a sample of service providers. RESULTS: The
      26 studies included in the review indicated the potential effectiveness of
      physical activity for people with dementia, including improvements in cognition
      and mood, behaviour and physical condition. Mechanisms of action and the link
      with outcomes were poorly defined and implemented.The mapping survey and related
      interviews showed that service providers were delivering a range of services
      broadly consistent with the scientific evidence. They tended to take a holistic
      view of possible benefits, and focused on enjoyment and well-being, more than
      specific cognitive, physical and behavioural outcomes highlighted in literature.
      Service providers needed more evidence based information and resources to develop
      services and realise their potential. CONCLUSION: Despite potential benefits
      demonstrated in literature and practice, there is a need for further research to
      optimise interventions and to consider some neglected issues including delivery
      at home and in communities; impacts for carers; physical activities through ADLs;
      and individual needs. Studies are needed which take a more holistic approach to
      the effects of physical activity, and outcomes should be broader and include
      mental health and wellbeing.

PMID- 24274625
TI  - Peptide-templated gold nanocluster beacon as a sensitive, label-free sensor for
      protein post-translational modification enzymes.
AB  - Protein post-translational modifications (PTMs), which are chemical modifications
      and most often regulated by enzymes, play key roles in functional proteomics.
      Detection of PTM enzymes, thus, is critical in the study of cell functioning and
      development of diagnostic and therapeutic tools. Herein, we develop a simple
      peptide-templated method to direct rapid synthesis of highly fluorescent gold
      nanoclusters (AuNCs) and interrogate the effect of enzymatic modifications on
      their luminescence. A new finding is that enzymes are able to exert chemical
      modifications on the peptide-templated AuNCs and quench their fluorescence, which
      furnishes the development of a real-time and label-free sensing strategy for PTM
      enzymes. Two PTM enzymes, histone deacetylase 1 and protein kinase A, have been
      employed to demonstrate the feasibility of this enzyme-responsive fluorescent
      nanocluster beacon. The results reveal that the AuNCs' fluorescence can be
      dynamically decreased with increasing concentration of the enzymes, and
      subpicomolar detection limits are readily achieved for both enzymes. The
      developed strategy can thus offer a useful, label-free biosensor platform for the
      detection of protein-modifying enzymes and their inhibitors in biomedical
      applications. 

PMID- 24274626
TI  - Using a shared parameter mixture model to estimate change during treatment when
      termination is related to recovery speed.
AB  - OBJECTIVE: This study demonstrates how to use a shared parameter mixture model
      (SPMM) in longitudinal psychotherapy studies to accommodate missingness that is
      due to a correlation between rate of improvement and termination of therapy.
      Traditional growth models assume that such a relationship does not exist (i.e.,
      assume that data are missing at random) and produce biased results if this
      assumption is incorrect. METHOD: We used longitudinal data from 4,676 patients
      enrolled in a naturalistic study of psychotherapy to compare results from a
      latent growth model and an SPMM. RESULTS: In this data set, estimates of the rate
      of improvement during therapy differed by 6.50%-6.66% across the two models,
      indicating that participants with steeper trajectories left psychotherapy
      earliest, thereby potentially biasing inference for the slope in the latent
      growth model. CONCLUSION: We conclude that reported estimates of change during
      therapy may be underestimated in naturalistic studies of therapy in which
      participants and their therapists determine the end of treatment. Because non
      randomly missing data can also occur in randomized controlled trials or in
      observational studies of development, the utility of the SPMM extends beyond
      naturalistic psychotherapy data.

PMID- 24274627
TI  - Does alliance predict symptoms throughout treatment, or is it the other way
      around?
AB  - OBJECTIVE: Scholars increasingly recognize that therapeutic alliance and
      symptomatic change are associated with one another. A common assumption is that
      alliance predicts symptomatic change. However, the issue is far from settled. One
      challenge in determining the causality is the establishment of temporal
      precedence showing that alliance, as opposed to previous symptomatic change,
      drives subsequent symptomatic reduction. METHOD: To make further advances in
      untangling this chicken-and-egg question, we employed autoregressive cross-lagged
      modeling over 4 time points in a sample of 149 depressive patients receiving
      supportive-expressive psychotherapy or clinical management combined with
      pharmacotherapy or clinical management combined with placebo. RESULTS: Using this
      methodology, we found that both alliance and symptoms across treatment made
      significant and unique contributions in predicting subsequent symptomatic levels
      throughout treatment. Additionally, alliance, but not symptoms, predicted
      subsequent alliance levels. No differences were found between treatments.
      CONCLUSIONS: Our findings imply that alliance temporally precedes symptomatic
      levels throughout treatment.

PMID- 24274628
TI  - Children's body fatness and prevalence of obesity in relation to height for age.
AB  - BACKGROUND: Children who are taller for their age tend to have higher BMI and, as
      a group, a greater prevalence of overweight/obesity. AIM: To examine the
      relationship between height for age with three measures of adiposity. SUBJECTS
      AND METHODS: Height, weight, BMI, % body fat (%BF) (by bioimpedance) and waist
      circumference (WC) were measured in 2298 Caucasian children (1251 boys) aged 4-14
      years. Standard deviation scores (SDS) were derived and cases divided into
      quartiles of height SDS. Mean BMI, %BF and WC SDSs were compared across
      quartiles. Prevalence of overweight/obesity, over-fat/obesity and abdominal
      overweight/obesity within each height for age quartile was determined. RESULTS:
      Mean BMI, %BF and WC SDSs increased with increasing quartile of height SDS.
      Overweight/obesity, overfat/obesity and abdominal overweight/obesity prevalence
      increased from the first quartile (8.8-13%) to the fourth quartile (32.7-45.5%)
      of height SDS. A significant rising trend in mean SDSs for BMI, %BF and WC was
      also observed with increasing height SDS in overweight/obese children only.
      CONCLUSION: A higher prevalence of excess weight, measured by BMI SDS among
      children taller for their age, is replicated when using %BF and WC. Height for
      age measurement has potential in screening children for later risk of obesity.

PMID- 24274629
TI  - Growth dynamics for DNA-guided nanoparticle crystallization.
AB  - Spherical nucleic acid (SNA) nanostructures assemble into a large variety of well
      defined crystalline superlattices via DNA-directed hybridization. Crystallities
      of SNA with various shapes emerge during the assembly process, which coalesce
      during coarsening, leading to polycrystalline materials. Here, we investigate the
      growth dynamics of SNAs into body-centered cubic superlattices and the
      coalescence of SNA aggregates using a colloidal model formulated from the
      competition of electrostatic core repulsions and localized DNA hybridization
      attractions. We find that the growth law of isolated SNA crystallities is well
      described by the power law t(1/2), in agreement with experimental observations.
      At later times, coalescence slows the growth dynamics considerably and is
      dependent on the orientational mismatch (misorientation angle) of the coalescing
      crystallites. Molecular dynamics simulations show that the misorientation angle
      decreases continually during the coalescence, which is a signature of the grain
      rotation induced coalescence mechanism. This mechanism is followed by the
      coarsening of a "neck" that develops at the boundary between the coalescing
      crystallites. Remarkably, we find faster coalescence dynamics for larger SNAs
      compared to smaller SNAs due to their enhanced surface diffusion, which more
      effectively reduces curvature at the boundary of two superlattices. These
      findings provide fundamental insight into the relationship between nanoparticle
      surface chemistry and its crystallite growth and coalescence. 

PMID- 24274630
TI  - InAs nanowires grown by metal-organic vapor-phase epitaxy (MOVPE) employing
      PS/PMMA diblock copolymer nanopatterning.
AB  - Dense arrays of indium arsenide (InAs) nanowire materials have been grown by
      selective-area metal-organic vapor-phase epitaxy (SA-MOVPE) using polystyrene-b
      poly(methyl methacrylate) (PS/PMMA) diblock copolymer (DBC) nanopatterning
      technique, which is a catalyst-free approach. Nanoscale openings were defined in
      a thin (~10 nm) SiNx layer deposited on a (111)B-oriented GaAs substrate using
      the DBC process and CF4 reactive ion etching (RIE), which served as a hard mask
      for the nanowire growth. InAs nanowires with diameters down to ~ 20 nm and
      micrometer-scale lengths were achieved with a density of ~ 5 * 10(10) cm(2). The
      nanowire structures were characterized by scanning electron microscopy and
      transmission electron microscopy, which indicate twin defects in a primary
      zincblende crystal structure and the absence of threading dislocation within the
      imaged regions.

PMID- 24274631
TI  - Reactive transport of iomeprol during stream-groundwater interactions.
AB  - The transport and biochemical transformations of the iodinated X-ray contrast
      medium (ICM) iomeprol were studied at the stream/groundwater interface. During a
      one-month field experiment piezometric pressure heads, temperatures, and
      concentrations of redox-sensitive species, iomeprol and 15 of its transformation
      products (TPs) were collected in stream- and groundwater. The data set was
      analyzed and transformation processes and rates identified by comparing
      conservative and reactive transport simulations. ICM and TP transformations were
      simulated as a cometabolic process during organic carbon degradation. Using
      iomeprol/TPs ratios as calibration constrain mitigated the uncertainties
      associated with the high variability of the ICM wastewater discharge into the
      investigated stream. The study provides evidence that biodegradation of ICM
      occurs at the field-scale also for predominantly denitrifying conditions. Under
      these anaerobically dominated field conditions shortest simulated half-life (21
      days) was in the same range as previously reported laboratory-determined half
      lives for aerobic conditions. 

PMID- 24274632
TI  - Systematic reviews and meta-analyses of diagnostic test accuracy.
AB  - Systematic reviews of diagnostic test accuracy summarize the accuracy, e.g. the
      sensitivity and specificity, of diagnostic tests in a systematic and transparent
      way. The aim of such a review is to investigate whether a test is sufficiently
      specific or sensitive to fit its role in practice, to compare the accuracy of two
      or more diagnostic tests, or to investigate where existing variation in results
      comes from. The search strategy should be broad and preferably fully reported, to
      enable readers to assess the completeness of it. Included studies usually have a
      cross-sectional design in which the tests of interest, ideally both the index
      test and its comparator, are evaluated against the reference standard. They
      should be a reflection of the situation that the review question refers to. The
      quality of included studies is assessed with the Quality Assessment of Diagnostic
      Accuracy Studies-2 checklist, containing items such as a consecutive and all
      inclusive patient selection process, blinding of index test and reference
      standard assessment, a valid reference standard, and complete verification of all
      included participants. Studies recruiting cases separately from (healthy)
      controls are regarded as bearing a high risk of bias. For meta-analysis, the
      bivariate model or the hierarchical summary receiver operating characteristic
      model is used. These models take into account potential threshold effects and the
      correlation between sensitivity and specificity. They also allow addition of
      covariates for investigatation of potential sources of heterogeneity. Finally,
      the results from the meta-analyses should be explained and interpreted for the
      reader, to be well understood. 

PMID- 24274633
TI  - The relationship between lymphovascular invasion and angiogenesis, hormone
      receptors, cell proliferation and survival in patients with primary operable
      invasive ductal breast cancer.
AB  - BACKGROUND: Several well-established tumour prognostic factors are used to guide
      the clinical management of patients with breast cancer. Lymphovascular invasion
      and angiogenesis have also been reported to have some promise as prognostic
      factors. The aim of the present study was to examine the prognostic value of
      tumour lymphovascular invasion and microvessel density compared with that of
      established prognostic factors in invasive ductal breast cancer. METHODS: In
      addition to hormone receptor status and Ki-67 proliferative activity,
      lymphovascular invasion and microvessel density and their relationship with
      survival were examined in patients with invasive ductal breast cancer. Full
      sections and tissue microarrays (n = 384 patients) were utilised to assess these
      factors and were scored by appropriate methods. RESULTS: On univariate analysis
      tumour size (P < 0.05), lymph node involvement (P < 0.01), lymphovascular
      invasion (P < 0.05), microvessel density (P < 0.05) and local- regional treatment
      (P < 0.01) were associated with poorer survival in ER negative tumours. On
      multivariate analysis in ER negative tumours lymph node involvement (P < 0.01)
      and local- regional treatment (P < 0.05) were independently associated with
      poorer cancer-specific survival. On univariate analysis tumour grade (P < 0.05),
      lymph node involvement (P < 0.001), HER-2 (P < 0.05), Ki-67 (P < 0.01) and
      lymphovascular invasion (P < 0.001) were associated with poorer survival in ER
      positive tumours. On multivariate analysis lymph node involvement (P < 0.001), Ki
      67 (P < 0.001) and lymphovascular invasion (P < 0.05) were independently
      associated with poorer cancer-specific survival in ER positive tumours.
      CONCLUSION: Lymphovascular invasion but not microvessel density was independently
      associated with poorer survival in patients with ER positive but not ER negative
      invasive ductal breast cancer.

PMID- 24274634
TI  - Solid lipid nanoparticles (SLNs) gels for topical delivery of aceclofenac in
      vitro and in vivo evaluation.
AB  - Solid lipid nanoparticles (SLN) are very potential formulations for topical
      delivery of anti-inflammatory and anti-arthritic drugs. The solid state of the
      lipid particles enable efficient drug encapsulation and controlled drug release.
      In the present study, the evaluation of different formulation parameters based on
      variation of concentration of lipid and cosurfactant was studied. The SLN gel
      formulations of the dispersions were compared to the SLN dispersions and with the
      marketed gel of aceclofenac. The SLNs were prepared by high speed homogenization
      and ultra-sonication method with fixed amount of aceclofenac (10%) and pluronic
      F68 (1.5%). The particle size, zeta potential and span of developed formulations
      was found to be within the range of 123 nm to 323 nm, -12.4 to -18.5 and 0.42 to
      0.86 respectively as the lipid concentration was increased from 7.5% to 40%. The
      highest entrapment efficiency was found to be 75% with the formulation having
      lipid concentration of 30% and 0.85% of phospholipon 90G. Permeation rate and
      controlled release property of xanthan gum loaded SLN gel formulations and SLN
      dispersion was studied through excised pig skin for 24hr. The drug release of SLN
      gel formulations was better controlled as compare to SLN dispersions. In vivo
      anti-inflammatory study showed that action of aceclofenac was enhanced for SLN
      dispersion and gel formulations. The results indicated the superiority of SLN
      based formulations for topical delivery of aceclofenac. 

PMID- 24274635
TI  - An introduction to fast dissolving oral thin film drug delivery systems: a
      review.
AB  - Many pharmaceutical companies are switching their products from tablets to fast
      dissolving oral thin films (OTFs). Films have all the advantages of tablets
      (precise dosage, easy administration) and those of liquid dosage forms (easy
      swallowing, rapid bioavailability). Statistics have shown that four out of five
      patients prefer orally disintegrating dosage forms over conventional solid oral
      dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with
      Central Nervous System disorders, have difficulty in swallowing or chewing solid
      dosage forms. Many of these patients are non-compliant in administering solid
      dosage forms due to fear of choking. OTFs when placed on the tip or the floor of
      the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and
      then disintegrate and/or dissolve to release the medication for local and/or
      systemic absorption. This technology provides a good platform for patent non-
      infringing product development and for increasing the patent life-cycle of the
      existing products. The application of fast dissolving oral thin films is not only
      limited to buccal fast dissolving system, but also expands to other applications
      like gastroretentive, sublingual delivery systems. This review highlights the
      composition including the details of various types of polymers both natural and
      synthetic, the different types of manufacturing techniques, packaging materials
      and evaluation tests for the OTFs. 

PMID- 24274636
TI  - Optimization of size and encapsulation efficiency of 5-FU loaded chitosan
      nanoparticles by response surface methodology.
AB  - The objective of this study was to optimize the particle size and encapsulation
      efficiency of chitosan nanoparticles loaded with 5-Fluorouracil (5-FU) by
      response surface methodology. Nanoparticles were prepared by ionic gelation
      method from chitosan and penta sodium triphosphate (TPP) at different
      combinations of chitosan viscosity, chitosan concentration and chitosan/TPP mass
      ratio according to the Box-Behnken experimental design. The particle size and
      encapsulation efficiency of prepared particles were measured by dynamic light
      scattering and UV spectroscopy, respectively, and the obtained data were
      subjected to multiple linear regression analysis followed by multi-attribute
      utility analysis to obtain a model for prediction of the optimum response. The
      optimum conditions for the production of 5-FU loaded chitosan nanoparticles were
      found to be low viscosity chitosan 0.5-1 mg/mL, middle viscosity chitosan 0.5-0.8
      mg/mL and high viscosity chitosan 0.5-0.75 mg/mL and chitosan/TPP mass ratio of 4
      or 6, yielding nanoparticles at the average diameter range of 114-188 nm and
      encapsulation efficiencies between 42-55%. 

PMID- 24274637
TI  - In situ NMR spectroscopy of supercapacitors: insight into the charge storage
      mechanism.
AB  - Electrochemical capacitors, commonly known as supercapacitors, are important
      energy storage devices with high power capabilities and long cycle lives. Here we
      report the development and application of in situ nuclear magnetic resonance
      (NMR) methodologies to study changes at the electrode-electrolyte interface in
      working devices as they charge and discharge. For a supercapacitor comprising
      activated carbon electrodes and an organic electrolyte, NMR experiments carried
      out at different charge states allow quantification of the number of charge
      storing species and show that there are at least two distinct charge storage
      regimes. At cell voltages below 0.75 V, electrolyte anions are increasingly
      desorbed from the carbon micropores at the negative electrode, while at the
      positive electrode there is little change in the number of anions that are
      adsorbed as the voltage is increased. However, above a cell voltage of 0.75 V,
      dramatic increases in the amount of adsorbed anions in the positive electrode are
      observed while anions continue to be desorbed at the negative electrode. NMR
      experiments with simultaneous cyclic voltammetry show that supercapacitor
      charging causes marked changes to the local environments of charge storing
      species, with periodic changes of their chemical shift observed. NMR calculations
      on a model carbon fragment show that the addition and removal of electrons from a
      delocalized system should lead to considerable increases in the nucleus
      independent chemical shift of nearby species, in agreement with our experimental
      observations. 

PMID- 24274638
TI  - Historical prevalence and distribution of avian influenza virus A(H7N9) among
      wild birds.
AB  - We examined 48 published studies for which sample sizes could be ascertained to
      determine the historic prevalence of influenza A(H7N9) virus in wild bird
      populations and reviewed GenBank data to further establish its distribution. Low
      prevalence (0.0093%) in Asia suggests > 30,000 samples would be required to
      detect the H7N9 subtype in wild birds. 

PMID- 24274639
TI  - Mean platelet volume as a potential prognostic marker in patients with acute
      mesenteric ischemia-retrospective study.
AB  - INTRODUCTION: We investigated prognostic parameters of patients who underwent
      surgical intervention for acute mesenteric ischemia by evaluating demographic
      characteristics and laboratory data on admission. METHODS: The hospital records
      of 30 patients who underwent surgical interventions due to acute mesenteric
      ischemia between January 2008 and December 2012, were reviewed retrospectively.
      The records were investigated with regard to demographic data, the presence of co
      morbid diseases, presenting complaints, time elapsed between symptom onset and
      hospital admission, laboratory findings at admission, findings at surgical
      exploration, surgical methods used, and treatment outcomes. The patients were
      divided into two groups, according to death (Group 1) or survival (Group 2), and
      the two groups were compared in terms of the specified parameters. RESULTS: Of
      the patients, 15 were male (50%) and 15 female (50%); their mean age was 71.4 (29
      94) years. Abdominal pain was the chief complaint in all patients (100%) and mean
      time from pain onset to hospital admission was 21 (1-72) h. In abdominal
      exploration, total small bowel (SB) ischemia and necrosis was found in 6 (20%)
      patients and other patients had subtotal SB, segmental SB, segmental SB with
      colon, or isolated colon ischemia. Treatment in 15 patients (50%) ended in
      mortality. Mean age (p = 0.038), urea (p = 0.002), AST (p < 0.001), ALT (p <
      0.001), mean platelet volume (MPV; p = 0.002), and amylase (p = 0.022) levels in
      Group 1 were significantly higher versus Group 2, whereas Ca (p = 0.024) and
      albumin (p = 0.002) levels were significantly lower. CONCLUSIONS: In this study,
      unlike other parameters that have been shown to be of prognostic significance in
      mesenteric ischemia, MPV values at presentation were higher among non-survivors
      than survivors.

PMID- 24274640
TI  - Clinical and forensic signs related to ethanol abuse: a mechanistic approach.
AB  - For good performance in clinical and forensic toxicology, it is important to be
      aware of the signs and symptoms related to xenobiotic exposure since they will
      assist clinicians to reach a useful and rapid diagnosis. This manuscript
      highlights and critically analyses clinical and forensic imaging related to
      ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are
      not necessarily related to liver disease are thoroughly discussed regarding its
      underlying mechanisms. This includes flushing and disulfiram reactions,
      urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda,
      "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple
      symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease),
      pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol
      syndrome, seborrheic dermatitis, sialosis and cancer.

PMID- 24274641
TI  - Multiple metachronous osteosarcomas in a patient with Li-Fraumeni syndrome.

PMID- 24274642
TI  - Melosuavines A-H, cytotoxic bisindole alkaloid derivatives from Melodinus
      suaveolens.
AB  - Eight new bisindole alkaloids, melosuavines A-C (1-3), having an aspidosperma
      scandine linkage, melosuavines D-F (4-6), possessing an aspidosperma-aspidosperma
      skeleton, and melosuavines G and H (7 and 8) of the aspidosperma-venalatonine
      type, tenuicausine (9), and melodinine J (10) were isolated from the twigs and
      leaves of Melodinus suaveolens. The structures of 1-8 were elucidated by
      extensive spectroscopic methods, and compounds 9 and 10 were identified by
      comparison with data in the literature. The relative configuration 9 was
      determined from the ROESY spectrum, and some NMR signals were reassigned.
      Compounds 1, 2, 4-6, 8, and 10 exhibited low micromolar cytotoxicity against one
      or more of five human cancer cell lines. 

PMID- 24274643
TI  - On-off-on fluorescent carbon dot nanosensor for recognition of chromium(VI) and
      ascorbic acid based on the inner filter effect.
AB  - Chromium(VI) [Cr(VI)] is considered as a severe environmental pollutant, due to
      its highly toxic and carcinogenic properties. Therefore, low cost, highly
      sensitive sensors for the determination of Cr(VI) are highly demanded. It is well
      known that highly luminescent carbon dots (CDs) have been successfully applied as
      fluorescent nanosensors for pH, ions, and molecular substances. In the present
      work, we have demonstrated an on-off fluorescent CD probe for detecting Cr(VI)
      based on the inner filter effect (IFE) because the absorption bands of Cr(IV)
      fully covered the emission and excitation bands of CDs. This CD-based nanosensor
      provides obvious advantages of simplicity, convenience, rapid response, high
      selectivity, and sensitivity, which have potential application for the detection
      of Cr(VI) in the environmental industry. In addition, because Cr(VI) can be
      reduced to low valent chromium species easily by reductant, resulting in the
      elimination of the IFE and recovery of CD fluorescence, the CD-Cr(VI) mixture
      could behave as an off-on type fluorescent probe for reductant. We employed
      ascorbic acid (AA) as an example molecule to demonstrate this off-on type
      fluorescent probe. 

PMID- 24274644
TI  - Cancer seeding contributes to intestinal anastomotic dehiscence.
AB  - BACKGROUND: Surgical wounds in cancer patients have a relatively high dehiscence
      rate. Although colon cancer resections are performed so as to include
      macroscopically non-involved tissues, some cancer cells can be present in the
      line of transection. The local healing process may facilitate proliferation of
      these localized cancer cells and the high cytokine concentration within the
      healing wound may also attract cancer cells from distant sites to migrate into
      the wound area. The growing tumor cells may then stretch the wound, hampering its
      contraction process. METHODS: The aim of the study was to monitor and compare,
      using immunohistochemical methods, the healing process of intestinal anastomosis
      in both normal rats and in rats with disseminated cancer (the CC531 colon cancer
      model). RESULTS: There was a significantly higher rate of anastomotic dehiscence
      in the group of rats with disseminated cancer, than in the group of normal rats.
      There were no significant differences between the two groups in the levels of
      mononuclear wound infiltration or of formation of connective tissue or new
      vessels. All anastomotic wounds in animals with disseminated cancer had abundant
      infiltrates of both migrating and proliferating cancer cells. CONCLUSIONS: We
      confirmed that the environment of a healing wound attracts cancer cells.
      Migration of cancer cells to the wound and centrifugal cancer proliferation may
      adversely affect the healing process and cause wound disruption.

PMID- 24274645
TI  - An asymptomatic annular patch on the palm.

PMID- 24274646
TI  - Cytochrome P450 and ischemic heart disease: current concepts and future
      directions.
AB  - INTRODUCTION: The P450 enzymes (P450s) mediate the biotransformation of several
      drugs, steroid hormones, eicosanoids, cholesterol, vitamins, fatty acids and bile
      acids, many of which affect cardiovascular homeostasis. Experimental studies have
      demonstrated that several P450s modulate important steps in the pathogenesis of
      ischemic heart disease (IHD). AREAS COVERED: This article discusses the current
      knowledge on i) the expression of P450s in cardiovascular and renal tissues; ii)
      the role of P450s in the pathophysiology of IHD, in particular the modulation of
      blood pressure and cardiac hypertrophy, coronary arterial tone, ischemia
      reperfusion injury and the metabolism of cardiovascular drugs; iii) the available
      evidence from observational studies on the association between P450 gene
      polymorphisms and risk of myocardial infarction (MI); and iv) suggestions for
      further research in this area. EXPERT OPINION: P450s exert important modulatory
      effects in experimental models of IHD and MI. However, observational studies have
      provided conflicting results on the association between P450 genetic
      polymorphisms and MI. Further, adequately powered studies are required to
      ascertain the biological and clinical impact of P450s on clinical IHD end-points,
      that is, fatal and nonfatal MI, revascularization and long-term outcomes post MI.
      Pharmacogenetic substudies of recently completed cardiovascular clinical trials
      might represent an alternative strategy in this context.

PMID- 24274647
TI  - Predator perception of Batesian mimicry and conspicuousness in a salamander.
AB  - In Batesian mimicry a palatable mimic deceives predators by resembling an
      unpalatable model. The evolution of Batesian mimicry relies on the visual
      capabilities of the potential predators, as prey detection provides the selective
      force driving evolutionary change. We compared the visual capabilities of several
      potential predators to test predictions stemming from the hypothesis of Batesian
      mimicry between two salamanders: the model species Notophthalmus viridescens, and
      polymorphic mimic, Plethodon cinereus. First, we found mimicry to be restricted
      to coloration, but not brightness. Second, only bird predators appeared able to
      discriminate between the colors of models and nonmimic P. cinereus. Third,
      estimates of salamander conspicuousness were background dependent, corresponding
      to predictions only for backgrounds against which salamanders are most active.
      These results support the hypothesis that birds influence the evolution of
      Batesian mimicry in P. cinereus, as they are the only group examined capable of
      differentiating N. viridescens and nonmimetic P. cinereus. Additionally, patterns
      of conspicuousness suggest that selection from predators may drive the evolution
      of conspicuousness in this system. This study confirms the expectation that the
      visual abilities of predators may influence the evolution of Batesian mimicry,
      but the role of conspicuousness may be more complex than previously thought. 

PMID- 24274648
TI  - Flow-induced structured phase in nonionic micellar solutions.
AB  - In this work, we consider the flow of a nonionic micellar solution (precursor)
      through an array of microposts, with focus on its microstructural and rheological
      evolution. The precursor contains polyoxyethylene(20) sorbitan monooleate (Tween
      80) and cosurfactant monolaurin (ML). An irreversible flow-induced structured
      phase (NI-FISP) emerges after the nonionic precursor flows through the hexagonal
      micropost arrays, when subjected to strain rates ~10(4) s(-1) and strain ~10(3).
      NI-FISP consists of close-looped micellar bundles and multiconnected micellar
      networks as evidenced by transmission electron microscopy (TEM) and cryo-electron
      microscopy (cryo-EM). We also conduct small-angle neutron scattering (SANS)
      measurements in both precursor and NI-FISP to illustrate the structural
      transition. We propose a potential mechanism for the NI-FISP formation that
      relies on the micropost arrays and the flow kinematics in the microdevice to
      induce entropic fluctuations in the micellar solution. Finally, we show that the
      rheological variation from a viscous precursor solution to a viscoelastic
      micellar structured phase is associated with the structural evolution from the
      precursor to NI-FISP.

PMID- 24274649
TI  - Comparison of 2f1-f2 DPOAE and 2f2-f1 DPOAE fine structure in young and middle
      aged adults.
AB  - OBJECTIVE: The 2f2-f1 DPOAE is not as popular as the 2f1-f2 DPOAE in the clinical
      realm as it is not as robust. However, it does have an advantage of being a
      predominantly reflection emission. The reflection component has been found to be
      sensitive to cochlear damage. Our objective was to compare the two types of DPOAE
      to track subtle changes due to aging. DESIGN: We used the most suitable stimulus
      parameters to record the fine structures of 2f2-f1 DPOAE and 2f1-f2 DPOAE for
      comparison in two groups of individuals. STUDY SAMPLE: Young adults and middle
      aged adults with normal hearing sensitivity participated in the experiment. Both
      ears of all participants were tested. RESULTS: Although reductions were noted in
      the both types of DPOAE in the middle-aged participants compared with the young
      adults, the decrease in amplitude of the 2f2-f1 DPOAE was found to be
      statistically significant. This corresponded with statistically significant
      reductions in the reflection component of the 2f1-f2 DPOAE. Reductions in the 2f2
      f1 DPOAE were found with both, high-level and low-level primaries. CONCLUSIONS:
      These results highlight the advantages of analysing fine structure data of the
      2f2-f1 DPOAE to track subtle cochlear changes in response to aging.

PMID- 24274650
TI  - Survival outcomes after radical and partial nephrectomy for clinical T2 renal
      tumours categorised by R.E.N.A.L. nephrometry score.
AB  - OBJECTIVE: We evaluated survival outcomes of partial nephrectomy (PN) and radical
      nephrectomy (RN) for clinical T2 renal masses (cT2RM) controlling for R.E.N.A.L.
      nephrometry score. PATIENTS AND METHODS: A two-centre study comprised of 202
      patients with cT2RM who underwent RN (122) or PN (80) between July 2002 and June
      2012 (median follow-up 41.5 months). Kaplan-Meier analysis compared overall
      survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS)
      among the entire cohort and within categories of R.E.N.A.L. nephrometry score of
      >=10 and <10. Association between procedure and PFS and OS was analysed using Cox
      proportional hazard. RESULTS: There were no significant differences between PN
      and RN in clinical T stage and R.E.N.A.L. nephrometry scores. For RN and PN, the
      5-year PFS was 69.8% and 79.9% (P = 0.115), CSS was 82.5% and 86.7% (P = 0.407),
      and OS was 80% and 83.3% (P = 0.291). Cox regression showed no association
      between RN vs PN and PFS; a R.E.N.A.L. nephrometry score of >=10 was associated
      with a shorter PFS (hazard ratio 6.69, P = 0.002). Kaplan-Meier analysis for RN
      vs PN showed no difference in PFS for entire cohort or within the R.E.N.A.L.
      nephrometry score categories of >=10 and <10. The PFS was better for those with
      R.E.N.A.L nephrometry scores of <10 vs >=10 (P < 0.001) and for cT2a vs cT2b
      tumours (P = 0.012). OS was no different between cT2a and cT2b tumours; patients
      with R.E.N.A.L. nephrometry scores of >=10 were more likely to die from disease
      (P < 0.001) or any cause (P < 0.001) vs those with R.E.N.A.L. nephrometry scores
      of <10. CONCLUSIONS: PN may be oncologically effective for cT2RM. A R.E.N.A.L
      nephrometry score of >=10 is negatively associated with OS among cT2RM compared
      with a score of <10 and provides additional risk assessment beyond clinical T
      stage. Further follow-up and prospective randomised investigation is requisite to
      confirm efficacy of PN for cT2RM.

PMID- 24274651
TI  - Biomolecular characterization of the levansucrase of Erwinia amylovora, a
      promising biocatalyst for the synthesis of fructooligosaccharides.
AB  - Erwinia amylovora is a plant pathogen that affects Rosaceae, such as apple and
      pear. In E. amylovora the fructans, produced by the action of a levansucrase
      (EaLsc), play a role in virulence and biofilm formation. Fructans are bioactive
      compounds, displaying health-promoting properties in their own right. Their use
      as food and feed supplements is increasing. In this study, we investigated the
      biomolecular properties of EaLsc using HPAEC-PAD, MALDI-TOF MS, and
      spectrophotometric assays. The enzyme, which was heterologously expressed in
      Escherichia coli in high yield, was shown to produce mainly
      fructooligosaccharides (FOSs) with a degree of polymerization between 3 and 6.
      The kinetic properties of EaLsc were similar to those of other phylogenetically
      related Gram-negative bacteria, but the good yield of FOSs, the product spectrum,
      and the straightforward production of the enzyme suggest that EaLsc is an
      interesting biocatalyst for future studies aimed at producing tailor-made
      fructans. 

PMID- 24274652
TI  - Dystrophic ossification on trachea and bronchus.

PMID- 24274653
TI  - Comparison of molecular subtype distribution in triple-negative inflammatory and
      non-inflammatory breast cancers.
AB  - INTRODUCTION: Because of its high rate of metastasis, inflammatory breast cancer
      (IBC) has a poor prognosis compared with non-inflammatory types of breast cancer
      (non-IBC). In a recent study, Lehmann and colleagues identified seven subtypes of
      triple-negative breast cancer (TNBC). We hypothesized that the distribution of
      TNBC subtypes differs between TN-IBC and TN-non-IBC. We determined the subtypes
      and compared clinical outcomes by subtype in TN-IBC and TN-non-IBC patients.
      METHODS: We determined TNBC subtypes in a TNBC cohort from the World IBC
      Consortium for which IBC status was known (39 cases of TN-IBC; 49 cases of TN-non
      IBC). We then determined the associations between TNBC subtypes and IBC status
      and compared clinical outcomes between TNBC subtypes. RESULTS: We found the seven
      subtypes exist in both TN-IBC and TN-non-IBC. We found no association between
      TNBC subtype and IBC status (P = 0.47). TNBC subtype did not predict recurrence
      free survival. IBC status was not a significant predictor of recurrence-free or
      overall survival in the TNBC cohort. CONCLUSIONS: Our data show that, like TN-non
      IBC, TN-IBC is a heterogeneous disease. Although clinical characteristics differ
      significantly between IBC and non-IBC, no unique IBC-specific TNBC subtypes were
      identified by mRNA gene-expression profiles of the tumor. Studies are needed to
      identify the subtle molecular or microenvironmental differences that contribute
      to the differing clinical behaviors between TN-IBC and TN-non-IBC.

PMID- 24274654
TI  - Zoonotic Chlamydiaceae species associated with trachoma, Nepal.
AB  - Trachoma is the leading cause of preventable blindness. Commercial assays do not
      discriminate among all Chlamydiaceae species that might be involved in trachoma.
      We investigated whether a commercial Micro-ArrayTube could discriminate
      Chlamydiaceae species in DNA extracted directly from conjunctival samples from
      101 trachoma patients in Nepal. To evaluate organism viability, we extracted RNA,
      reverse transcribed it, and subjected it to quantitative real-time PCR. We found
      that 71 (70.3%) villagers were infected. ArrayTube sensitivity was 91.7% and
      specificity was 100% compared with that of real-time PCR. Concordance between
      genotypes detected by microarray and ompA genotyping was 100%. Species
      distribution included 54 (76%) single infections with Chlamydia trachomatis, C.
      psittaci, C. suis, or C. pecorum, and 17 (24%) mixed infections that includied C.
      pneumoniae. Ocular infections were caused by 5 Chlamydiaceae species. Additional
      studies of trachoma pathogenesis involving Chlamydiaceae species other than C.
      trachomatis and their zoonotic origins are needed. 

PMID- 24274656
TI  - Trends in thin body stature among Japanese male adolescents, 2003-2012.
AB  - BACKGROUND: The desire for thin body stature and unhealthy eating behaviours have
      spread among Japanese boys. The prevalence of thinness in boys is expected to
      increase; however, recent trends have not been reported. AIM: To describe changes
      in the distribution of body mass index (BMI) of Japanese boys, from 2003 to 2012.
      SUBJECTS AND METHODS: BMI distribution changes were studied in 2599 relatively
      affluent Japanese children and adolescents, aged 12.5-17.5 years, during 2003
      2012. The 2003 and 2004 data were combined and compared to the combined 2011 and
      2012 data. Tukey mean-difference plots were used to study the direction and
      magnitude of shifts in BMI distributions. RESULTS: Prevalence of thinness has
      progressively increased from 2.8-4.7% in 2003-2004 to 5.1-7.6% in 2011-2012 in
      Japanese boys. Tukey plots showed that the increases in the prevalence of
      thinness are related to shifts in the entire distribution of BMI in the sample.
      CONCLUSION: Thin body stature was documented in increasing proportion of Japanese
      male adolescents. BMI z-scores decreased across the entire BMI centile spectrums,
      indicating that the whole school population may be at risk of thinness.

PMID- 24274657
TI  - Biotemplated synthesis of PZT nanowires.
AB  - Piezoelectric nanowires are an important class of smart materials for next
      generation applications including energy harvesting, robotic actuation, and
      bioMEMS. Lead zirconate titanate (PZT), in particular, has attracted significant
      attention, owing to its superior electromechanical conversion performance. Yet,
      the ability to synthesize crystalline PZT nanowires with well-controlled
      properties remains a challenge. Applications of common nanosynthesis methods to
      PZT are hampered by issues such as slow kinetics, lack of suitable catalysts, and
      harsh reaction conditions. Here we report a versatile biomimetic method, in which
      biotemplates are used to define PZT nanostructures, allowing for rational control
      over composition and crystallinity. Specifically, stoichiometric PZT nanowires
      were synthesized using both polysaccharide (alginate) and bacteriophage
      templates. The wires possessed measured piezoelectric constants of up to 132 pm/V
      after poling, among the highest reported for PZT nanomaterials. Further,
      integrated devices can generate up to 0.820 MUW/cm(2) of power. These results
      suggest that biotemplated piezoelectric nanowires are attractive candidates for
      stimuli-responsive nanosensors, adaptive nanoactuators, and nanoscale energy
      harvesters. 

PMID- 24274655
TI  - Micro total analysis systems: fundamental advances and biological applications.

PMID- 24274658
TI  - Phenotypic, immunologic, and clinical characteristics of patients with
      nontuberculous mycobacterial lung disease in Korea.
AB  - BACKGROUND: This study aimed to elucidate the phenotypic, immunologic, and
      clinical characteristics of Korean patients with nontuberculous mycobacterial
      (NTM) lung disease and compare them with non-NTM bronchiectasis (BE) patients.
      METHODS: We prospectively recruited patients between 20 and 80 years of age who
      had nodular BE type NTM lung disease. Phenotypic, immunologic, and clinical
      characteristics were evaluated through physical examination, laboratory tests,
      pulmonary function tests, and radiographic examinations. Questionnaires were also
      answered. The results of the evaluations were compared with the results of non
      NTM BE patients. RESULTS: A total of 84 patients with NTM lung disease and 47 non
      NTM BE patients participated in the study. Mycobacterium avium complex lung
      disease and M. abscessus lung disease were most common. Patients with NTM lung
      disease had lower body mass index than non-NTM BE patients. Scoliosis was
      observed more frequently in patients with NTM lung disease than in non-NTM BE
      patients. CONCLUSIONS: Significant similarities were seen between Korean patients
      with NTM lung disease and patients from other countries. Differences in
      phenotypic and clinical characteristics between NTM lung disease and non-NTM BE
      patients suggest differences in the immunopathogenesis of NTM lung disease and
      non-NTM BE. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Registration
      number; NCT01616745.

PMID- 24274659
TI  - Microbiological reduction of Sb(V) in anoxic freshwater sediments.
AB  - Microbiological reduction of millimolar concentrations of Sb(V) to Sb(III) was
      observed in anoxic sediments from two freshwater settings: (1) a Sb- and As
      contaminated mine site (Stibnite Mine) in central Idaho and 2) an uncontaminated
      suburban lake (Searsville Lake) in the San Francisco Bay Area. Rates of Sb(V)
      reduction in anoxic sediment microcosms and enrichment cultures were enhanced by
      amendment with lactate or acetate as electron donors but not by H2, and no
      reduction occurred in sterilized controls. Addition of 2-(14)C-acetate to
      Stibnite Mine microcosms resulted in the production of (14)CO2 coupled to Sb(V)
      reduction, suggesting that this process proceeds by a dissimilatory respiratory
      pathway in those sediments. Antimony(V) reduction in Searsville Lake sediments
      was not coupled to acetate mineralization and may be associated with Sb
      resistance. The microcosms and enrichment cultures also reduced sulfate, and the
      precipitation of insoluble Sb(III)-sulfide complexes was a major sink for reduced
      Sb. The reduction of Sb(V) by Stibnite Mine sediments was inhibited by As(V),
      suggesting that As(V) is a preferred electron acceptor for the indigenous
      community. These findings indicate a novel pathway for anaerobic microbiological
      respiration and suggest that communities capable of reducing high concentrations
      of Sb(V) commonly occur naturally in the environment. 

PMID- 24274660
TI  - Patients' socioeconomic status and their evaluations of primary care in Hong
      Kong.
AB  - BACKGROUND: Strengthening primary care is key to Hong Kong's ongoing health
      system reform. Primary care remains unregulated, private sector dominated and
      financed mainly out-of-pocket. This study sought to examine the association
      between patients' socioeconomic status (SES), source of health payments and the
      quality of primary care they accessed to inform policy discussions. METHODS: Data
      was collected from 1,994 respondents in a stratified random telephone survey with
      a 68% response rate, using the validated primary care assessment tool (PCAT).
      Education, household-income and type of housing were selected as indicators of
      SES. Multivariable ordinal logistic regression models were created to examine
      associations between indicators of SES and scores of quality. RESULTS: Higher
      household-income was most significantly associated with better experiences of
      quality. Respondents with HK$ 15000-39999 (USD1934-5158) and HK$ 40000 (USD5159)
      and above were 47% (OR 1.47, 95% CI 1.10-1.96) and 2 times (OR 2.07, 95% CI 1.38
      3.09) more likely to experience better quality than the lowest-income group
      respectively. Income group HK$ 40000 (USD5159) and above was 84% more likely to
      have better utilization (OR 1.84, 95% CI (1.21-2.78), and 2 times more likely to
      receive better comprehensiveness (OR 1.90, 95% CI 1.26-2.87). Patients who used
      only private insurance were 80% (OR 1.80, 95% CI 1.20-2.68) more likely to
      experience better quality than those who paid out-of-pocket. CONCLUSIONS: Our
      results show that the quality of primary care experienced in HK tended to be
      higher for those who had higher income and private insurance, and were able to
      pay out-of-pocket for the care. This indicated that the inequality in primary
      care is likely to be related with the private dominated primary care system in
      Hong Kong. More public responsibility on primary health care should be sought for
      in HK and similar contexts to reduce the inequality in primary care.

PMID- 24274661
TI  - Antiretroviral therapy for initial human immunodeficiency virus/AIDS treatment:
      critical appraisal of the evidence from over 100 randomized trials and 400
      systematic reviews and meta-analyses.
AB  - There have been over 100 randomized clinical trials (RCTs) of diverse regimens of
      antiretroviral therapy for treatment-naive human immunodeficiency virus-positive
      patients. A further 400 systematic reviews and meta-analyses are informed by
      these trials. There are, however, difficulties in using systematic reviews and
      meta-analyses of this clinical evidence to inform guidelines and clinical
      practice. Several issues can make the interpretation of comparative effectiveness
      challenging. In this article, we review the key challenges in interpreting
      multiple trials in this population. We specifically examine the network geometry
      of the clinical trial comparisons, the predominance of non-inferiority trial
      designs, issues related to potential class effects, heterogeneous documentation
      of adverse events, and a relative lack of RCTs that reflect specific current
      clinical guideline recommendations. We conclude with recommendations for future
      clinical trials and meta-analyses. 

PMID- 24274662
TI  - Aluminum for plasmonics.
AB  - Unlike silver and gold, aluminum has material properties that enable strong
      plasmon resonances spanning much of the visible region of the spectrum and into
      the ultraviolet. This extended response, combined with its natural abundance, low
      cost, and amenability to manufacturing processes, makes aluminum a highly
      promising material for commercial applications. Fabricating Al-based
      nanostructures whose optical properties correspond with theoretical predictions,
      however, can be a challenge. In this work, the Al plasmon resonance is observed
      to be remarkably sensitive to the presence of oxide within the metal. For Al
      nanodisks, we observe that the energy of the plasmon resonance is determined by,
      and serves as an optical reporter of, the percentage of oxide present within the
      Al. This understanding paves the way toward the use of aluminum as a low-cost
      plasmonic material with properties and potential applications similar to those of
      the coinage metals. 

PMID- 24274663
TI  - Evaluation of two enzyme-linked immunosorbent assays for serodiagnosis of
      Aleutian mink disease virus infection in mink.
AB  - BACKGROUND: Aleutian disease in mink is caused by infection with Aleutian mink
      disease virus (AMDV). In Sweden, the infection most commonly causes classical
      Aleutian disease in which the immune system fails to neutralize the virus and the
      infection becomes persistent. Diagnosis of AMDV infection is based on serological
      methods that detect virus-specific antibodies. Traditionally
      counterimmunoelectrophoresis (CIEP) has been the preferred method, but in order
      to enable automation interest has been paid to other antibody detecting systems.
      Recently, at least two different ELISA systems that detect antibodies to AMDV
      have been manufactured; one is based on an in vitro grown AMDV as antigen, and
      the other system is based on the AMDV capsid protein VP2 as antigen. The aim of
      this study was to evaluate the two ELISA systems for detection of antibodies to
      AMDV using CIEP as the gold standard. RESULTS: When employing the mean optical
      density of the samples from CIEP negative mink plus three standard deviations as
      cut-off value, the ELISA with the VP2 antigen had a sensitivity of 99.7% and a
      specificity of 98.3% compared to CIEP (n = 364). Analysis of samples with the
      AMDV-G antigen based ELISA employing an assay cut-off value based on the negative
      control samples, as suggested by the manufacturer, resulted in a sensitivity of
      54.3% and a specificity of 93.2% with reference to CIEP as the gold standard (n =
      359). When employing the mean optical density of the samples from CIEP negative
      mink plus three standard deviations as cut-off value, the AMDV-G ELISA had a
      sensitivity of 37.6% and a specificity of 98.3%. CONCLUSIONS: The ELISA system
      based on VP2 antigen had high sensitivity and specificity, and was concluded to
      be an alternative to the CIEP as a diagnostic tool for AMDV antibodies. In
      contrast, the AMDV-G ELISA suffered from low sensitivity when compared to CIEP.

PMID- 24274664
TI  - Lack of MERS coronavirus neutralizing antibodies in humans, eastern province,
      Saudi Arabia.
AB  - We used a lentiviral vector bearing the viral spike protein to detect
      neutralizing antibodies against Middle East respiratory syndrome coronavirus
      (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268
      samples tested displayed neutralizing activity, which suggests that MERS-CoV
      infections in humans are infrequent in this province. 

PMID- 24274665
TI  - Tuning reactivity and electronic properties through ligand reorganization within
      a cerium heterobimetallic framework.
AB  - Cerium compounds have played vital roles in organic, inorganic, and materials
      chemistry due to their reversible redox chemistry between trivalent and
      tetravalent oxidation states. However, attempts to rationally access molecular
      cerium complexes in both oxidation states have been frustrated by unpredictable
      reactivity in cerium(III) oxidation chemistry. Such oxidation reactions are
      limited by steric saturation at the metal ion, which can result in high energy
      activation barriers for electron transfer. An alternative approach has been
      realized using a rare earth/alkali metal/1,1'-BINOLate (REMB) heterobimetallic
      framework, which uses redox-inactive metals within the secondary coordination
      sphere to control ligand reorganization. The rational syntheses of functionalized
      cerium(IV) products and a mechanistic examination of the role of ligand
      reorganization in cerium(III) oxidation are presented. 

PMID- 24274666
TI  - Association between serum mercury concentration and leukocyte differential count
      in children.
AB  - There have been a number of animal studies on the immunological effects of
      mercury. However, there is a lack of studies investigating the effects of mercury
      in children. We investigated the association between serum mercury and leukocyte
      differential count in Korean children. The relationship between mercury and
      leukocyte differential count (segment, lymphocyte, monocyte, basophil, and
      eosinophil counts) was analyzed by multivariate linear analysis adjusted for sex,
      BMI, parental smoking, lead, cadmium, and allergic sensitization in 311 children.
      Mercury showed a positive correlation with lymphocyte count (coefficient 113.8,
      95% confidence interval 26.7-200.9). However, mercury was not associated with
      total leukocyte, segment, monocyte, basophil, or eosinophil count. Mercury was
      associated with the increased of lymphocyte count in Korean children. Further
      studies will be required to ascertain the clinical significance of this
      association. 

PMID- 24274667
TI  - Hepatotoxicity in rats induced by the poisonous dreamfish (Sarpa salpa).
AB  - AIMS: The present study was aimed to assess the cytotoxic effects of not-yet
      identified compounds present in organ extracts of Sarpa salpa, collected in
      autumn, the period with a peak in health problems. METHODS: The toxicity was
      assessed by mouse bioassay of extract of the fish's organs. Wistar rats received
      daily extracts of different organs of S. salpa by gastric gavage for 7 d (0.3 ml
      of extract/100 g body weight, BW). The dose of tissue extracts of viscera, liver,
      brain and flesh of S. salpa administered to rats were as follows: 17.2, 31.3,
      205, 266 mg/100g BW, respectively. No deaths occurred during the period of
      treatment. RESULTS: The lethal dose (LD50%) determined for the crude ciguatoxin
      (neurotoxins) extracts of viscera, liver, brain and flesh of S. salpa were as
      follows: 1.2, 2.2, 14.4, 18.6 g/kg mouse, respectively. Changes in locomotor
      activity during the first 2 h and failure breathing and no evident signs of
      gastrointestinal problems were recorded. We observed: (1) Induction of oxidative
      stress, indicated by an increase in lipid peroxidation (TBARS) in groups that
      received extracts of liver (+490%) or viscera (+592%). Accompanied by a
      significant decrease in antioxidant enzyme activities (SOD, CAT, GPx) in liver
      tissue by 15%, 17%, 18% (LT: animals receiving liver extracts) and by 19%, 22%,
      22% (VT: animals receiving viscera extracts), respectively. In contrast the
      administration of extracts of flesh and brain induced an increase in antioxidant
      enzyme activities (SOD, CAT, GPx) in liver tissue by 15%, 19%, 15% (FT: flesh
      extract) and 18%, 55%, 55% (BT: brain extract), respectively; (2) A significant
      increase in total metallothionein levels in liver tissue was recorded in (FT),
      (BT), (LT) and (VT) by 55%, 88%, 255% and 277%, respectively, (3) The
      histological findings confirmed the biochemical results. CONCLUSIONS: Liver and
      especially visceral part of S. salpa presented toxicity, which clearly indicates
      the danger of using this fish as food.

PMID- 24274668
TI  - Structural characterization of the heterobactin siderophores from Rhodococcus
      erythropolis PR4 and elucidation of their biosynthetic machinery.
AB  - In this study, the isolation, the structural characterization, and the
      elucidation of the biosynthetic origin of heterobactins, catecholate-hydroxamate
      mixed-type siderophores from Rhodococcus erythropolis PR4, are reported. The
      structure elucidation of heterobactin A was accomplished via MS(n) analysis and
      NMR spectroscopy and revealed the noteworthy presence of a peptide bond between
      the guanidine group of an arginine residue and a 2,3-dihydroxybenzoate moiety.
      The two heterobactin S1 and S2 variants are derivatives of heterobactin A that
      have sulfonation modifications on the aromatic rings. The bioinformatic analysis
      of the R. erythropolis PR4 genome and the subsequent genetic and biochemical
      characterization of the putative biosynthetic machinery identified the gene
      cluster responsible for the biosynthesis of the heterobactins. Interestingly, the
      HtbG NRPS presents an unprecedented C-PCP-A domain organization within the second
      module of the synthetase that may help the correct elongation of the peptide
      intermediate. Finally, the present work revises the structure of heterobactin A
      that was described by Carrano et al. in 2001. 

PMID- 24274669
TI  - Adverse drug reaction reporting related to the administration of antibiotics in
      hospitalized pediatric patients in Greece.
AB  - INTRODUCTION: Pharmacosurveillance during the administration of antibiotics is of
      extreme importance in paediatric patients given their different physiology and
      adverse drug reaction (ADR) profile compared to the adult population. Systematic
      reviews show that one in ten hospitalised children will experience ADRs.
      Administration of antibiotics is among the leading causes of such ADRs. The aim
      of this study was to assess ADRs reporting related to the administration of
      antibiotics in hospitalized paediatric patients in Greece. METHODS: A cross
      sectional study was conducted over a seven month period (January to July 2012) in
      paediatric departments in Greece. A self-administered questionnaire was
      distributed to a total of 750 health professionals providing paediatric care in 3
      specialized paediatric hospitals and 33 paediatric departments in general and
      university hospitals. Descriptive and multivariate statistical analyses were
      performed. Levels of significance were two-tailed and statistical significance
      was set at P =0.05. RESULTS: Overall, 576 out of 750 questionnaires were returned
      completed, at a response rate of 76.8%. ADRs related to antibiotics were reported
      by 44.8% of nurses and 23.7% of doctors as occurring often/very often during
      their practice. 45% of doctors reported amoxicillin/clavulanic acid as the drug
      with the most frequent ADRs. Overall, 63% of nurses and 32.7% of doctors stated
      they had never reported ADRs. Doctors used yellow cards more often than nurses
      (65.2% vs 33.9%). Only 48.4% of doctors and 35.9% of nurses knew that ADR
      reporting constitutes part of their professional duties. CONCLUSIONS: ADRs
      following antibiotic administration are common in paediatric practice in Greece;
      however, underreporting remains a significant problem.

PMID- 24274670
TI  - Targeting chemophotothermal therapy of hepatoma by gold nanorods/graphene oxide
      core/shell nanocomposites.
AB  - Nanographene oxide (NGO) are highly suitable to be the shells of inorganic
      nanomaterials to enhance their biocompatibility and hydrophilicity for biomedical
      applications while retaining their useful photonic, magnetic, or radiological
      functions. In this study, a novel nanostructure with gold nanorods (AuNRs)
      encapsulated in NGO shells is developed to be an ultraefficient chemophotothermal
      cancer therapy agent. The NGO shells decrease the toxicity of surfactant-coated
      AuNRs and provide anchor points for the conjugation of hyaluronic acid (HA). The
      HA-conjugated NGO-enwrapped AuNR nanocomposites (NGOHA-AuNRs) perform higher
      photothermal efficiency than AuNRs and have the capability of targeting hepatoma
      Huh-7 cells. NGOHA-AuNR is applied to load doxorubicin (DOX), and it exhibits pH
      responsive and near-infrared light-triggered drug-release properties.
      Chemophotothermal combined therapy by NGOHA-AuNRs-DOX performs 1.5-fold and 4
      fold higher targeting cell death rates than single chemotherapy and photothermal
      therapy, respectively, with biosafety to nontargeting cells simultaneously.
      Furthermore, our strategy could be extended to constructing other NGO
      encapsulated functional nanomaterial-based carrier systems.

PMID- 24274671
TI  - Functional tongue reconstruction with the anterolateral thigh flap.
AB  - BACKGROUND: A retrospective study was conducted to evaluate the advantages of
      anterolateral thigh (ALT) flap in tongue reconstruction. METHOD: From September
      2008 to February 2012, patients receiving ALT flap tongue reconstruction were
      included in the study. Patients undergoing ALT flap were compared with those
      undergoing similar surgery with radial forearm flap (RFF). The medical records of
      the included patients were reviewed, and a questionnaire was used to assess
      acceptability of the surgery. RESULTS: All flaps (both ALT and RFF) were
      successful In the ALT group, most patients were satisfied with the appearance of
      the reconstructed tongue and the intelligibility of their speech, and there were
      fewer complications with this technique compared with the RFF. CONCLUSION: The
      ALT flap is an ideal method for tongue reconstruction. The thickness and volume
      of the ALT flap can be adjusted based on the individual extent of the defect, and
      it can not only provide bulk but also ensure mobility, and it has other
      advantages also, including a long pedicle and low donor site morbidity.

PMID- 24274672
TI  - Papillary eccrine adenoma should not be mistaken for aggressive digital papillary
      adenocarcinoma.

PMID- 24274673
TI  - Curvature of capillary bridges as a competition between wetting and confinement.
AB  - We consider the shape evolution of non-axisymmetric capillary bridges in slit
      pore geometry as the pore height is increased at constant volume. Experiments and
      finite element simulations using Surface Evolver have shown that as the height of
      the pore is increased the mean curvature of the bridge, and hence Laplace
      pressure, changes its sign from negative to positive. Here we propose an
      intuitive explanation of this surprising phenomenon. We suggest that it is the
      balance between the confinement and the wetting properties of the supporting
      strips that causes the change in sign of the Laplace pressure. The theory
      proposed relies on three simple approximations, which are tested individually,
      and is in good agreement with experiments and simulations in the regime where the
      curvature transition from negative to positive takes place. Theoretical arguments
      take into account only the wetting properties and geometry of the system (the
      width and height of the pore). Along with the formula for the curvature, we
      derive also a relation for the pinning angle of the capillary bridge, which is
      also verified experimentally. 

PMID- 24274674
TI  - Prevalence of dyslipidaemia in patients with renal cell carcinoma: a case-control
      study in China.
AB  - OBJECTIVE: To examine the prevalence of dyslipidaemia in patients with renal cell
      carcinoma (RCC) in a Chinese population. PATIENTS AND METHODS: In all, 550
      histologically confirmed RCC cases and 570 controls, matched for age and sex were
      included. Total cholesterol, triglyceride, low-density lipoprotein (LDL) and high
      density lipoprotein (HDL) were assessed before treatment using standard
      techniques. The lipid profiles were defined as 'normal', 'borderline high',
      'high' and 'low' according to Chinese Guidelines on Adult Dyslipidaemia. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated using
      unconditional logistic regression in both unadjusted and adjusted models.
      RESULTS: Abnormal LDL elevation was common in RCC cases compared with controls (P
      < 0.001). Results for total cholesterol, triglyceride and HDL levels between
      groups were insignificant. The OR for RCC for high levels of LDL (>=160 mg/dL)
      compared with those with a normal LDL profile was 4.675 (95% CI 1.900-11.500).
      After adjustment for age, gender, body mass index, smoking status, hypertension,
      diabetes, total cholesterol and triglyceride, the coexistence of high levels of
      LDL and RCC was large and statistically significant (OR 8.955, 95% CI 3.371
      23.786). There was a significant coexistence of RCC for participants with high
      LDL levels when subgroups of cases with clear cell subtypes and advanced T stages
      were compared with controls. CONCLUSION: Abnormal LDL elevation was prevalent in
      Chinese patients with RCC. The results remain to be evaluated in prospective
      cohorts.

PMID- 24274675
TI  - The rate test of speciation: estimating the likelihood of non-allopatric
      speciation from reproductive isolation rates in Drosophila.
AB  - Among the most debated subjects in speciation is the question of its mode.
      Although allopatric (geographical) speciation is assumed the null model, the
      importance of parapatric and sympatric speciation is extremely difficult to
      assess and remains controversial. Here I develop a novel approach to distinguish
      these modes of speciation by studying the evolution of reproductive isolation
      (RI) among taxa. I focus on the Drosophila genus, for which measures of RI are
      known. First, I incorporate RI into age-range correlations. Plots show that
      almost all cases of weak RI are between allopatric taxa whereas sympatric taxa
      have strong RI. This either implies that most reproductive isolation (RI) was
      initiated in allopatry or that RI evolves too rapidly in sympatry to be captured
      at incipient stages. To distinguish between these explanations, I develop a new
      "rate test of speciation" that estimates the likelihood of non-allopatric
      speciation given the distribution of RI rates in allopatry versus sympatry. Most
      sympatric taxa were found to have likely initiated RI in allopatry. However, two
      putative candidate species pairs for non-allopatric speciation were identified
      (5% of known Drosophila). In total, this study shows how using RI measures can
      greatly inform us about the geographical mode of speciation in nature. 

PMID- 24274676
TI  - Estimates of the number of adults in England, Wales, and Scotland with a hearing
      loss.

PMID- 24274677
TI  - GaAs-Fe3Si core-shell nanowires: nanobar magnets.
AB  - Semiconductor-ferromagnet GaAs-Fe3Si core-shell nanowires were grown by molecular
      beam epitaxy and analyzed by scanning and transmission electron microscopy, X-ray
      diffraction, Mossbauer spectroscopy, and magnetic force microscopy. We obtained
      closed and smooth Fe3Si shells with a crystalline structure that show
      ferromagnetic properties with magnetizations along the nanowire axis
      (perpendicular to the substrate). Such nanobar magnets are promising candidates
      to enable the fabrication of new forward-looking devices in the field of
      spintronics and magnetic recording. 

PMID- 24274678
TI  - Adsorption of beta-glucosidases in two commercial preparations onto pretreated
      biomass and lignin.
AB  - BACKGROUND: Enzyme recycling is a method to reduce the production costs for
      advanced bioethanol by lowering the overall use of enzymes. Commercial cellulase
      preparations consist of many different enzymes that are important for efficient
      and complete cellulose (and hemicellulose) hydrolysis. This abundance of
      different activities complicates enzyme recycling since the individual enzymes
      behave differently in the process. Previously, the general perception was that
      beta-glucosidases could easily be recycled via the liquid phase, as they have
      mostly been observed not to adsorb to pretreated biomass or only adsorb to a
      minor extent. RESULTS: The results from this study with Cellic(r) CTec2 revealed
      that the vast majority of the beta-glucosidase activity was lost from the liquid
      phase and was adsorbed to the residual biomass during hydrolysis and
      fermentation. Adsorption studies with beta-glucosidases in two commercial
      preparations (Novozym 188 and Cellic(r) CTec2) to substrates mimicking the
      components in pretreated wheat straw revealed that the Aspergillus niger beta
      glucosidase in Novozym 188 did not adsorb significantly to any of the components
      in pretreated wheat straw, whereas the beta-glucosidase in Cellic(r) CTec2
      adsorbed strongly to lignin.The extent of adsorption of beta-glucosidase from
      Cellic(r) CTec2 was affected by both type of biomass and pretreatment method.
      With approximately 65% of the beta-glucosidases from Cellic(r) CTec2 adsorbed
      onto lignin from pretreated wheat straw, the activity of the beta-glucosidases in
      the slurry decreased by only 15%. This demonstrated that some enzyme remained
      active despite being bound. It was possible to reduce the adsorption of Cellic(r)
      CTec2 beta-glucosidase to lignin from pretreated wheat straw by addition of
      bovine serum albumin or poly(ethylene glycol). CONCLUSIONS: Contrary to the beta
      glucosidases in Novozym 188, the beta-glucosidases in Cellic(r) CTec2 adsorb
      significantly to lignin. The lignin adsorption observed for Cellic(r) CTec2 is
      usually not a problem during hydrolysis and fermentation since most of the
      catalytic activity is retained. However, adsorption of beta-glucosidases to
      lignin may prove to be a problem when trying to recycle enzymes in the production
      of advanced bioethanol.

PMID- 24274679
TI  - The association of therapist empathy and synchrony in vocally encoded arousal.
AB  - Empathy is a critical ingredient in motivational interviewing (MI) and in
      psychotherapy generally. It is typically defined as the ability to experience and
      understand the feelings of another. Basic science indicates that empathy is
      related to the development of synchrony in dyads. However, in clinical research,
      empathy has proved difficult to operationalize and measure, and has mostly relied
      on the felt sense of observers, clients, or therapists. We extracted estimates of
      therapist and standardized patient (SP) vocally encoded arousal (mean fundamental
      frequency; mean f0) in 89 MI sessions with high and low empathy ratings from
      independent observers. We hypothesized (a) therapist and SP mean f0 would be
      correlated and (b) the correlation of therapist and SP mean f0 would be greater
      in sessions with high empathy as compared with low. On the basis of a
      multivariate mixed model, the correlation between therapist and SP mean f0 was
      large (r = .71) and close to 0 in randomly assigned therapist-SP dyads (r = 
      .08). The association was higher in sessions with high empathy ratings (r = .80)
      than in sessions with low ratings (r = .36). There was strong evidence for vocal
      synchrony in clinical dyads as well as for the association of synchrony with
      empathy ratings, illustrating the relevance of basic psychological processes to
      clinical interactions. These findings provide initial evidence for an objective
      and nonobtrusive method for assessing therapist performance. Novel indicators of
      therapist empathy may have implications for the study of MI process as well as
      the training of therapists generally. (PsycINFO Database Record (c) 2014 APA, all
      rights reserved). 

PMID- 24274680
TI  - Pneumonia burden in elderly patients: a classification algorithm using
      administrative data.
AB  - BACKGROUND: Pneumonia has traditionally been classified into two subtypes:
      community-acquired pneumonia (CAP) and nosocomial pneumonia (NP). Recently, a new
      entity has been defined, called healthcare-associated pneumonia (HCAP). Few
      studies have investigated the potential of population-based, electronic,
      healthcare databases to identify the incidences of these three subtypes of
      pneumonia. The aim of this study was to estimate the burden of the three subtypes
      of pneumonia in elderly patients (aged 65+ years) in a large region of central
      Italy. METHODS: A retrospective cohort study was performed using linked regional
      Hospital Information System and Mortality Register. All episodes of pneumonia in
      elderly patients, who were discharged from the hospital in 2006-2008, were
      selected for the study. Following a validated ICD-9-coding algorithm, incidents
      of pneumonia events were classified into three groups (HCAP; probable nosocomial
      pneumonia, PNP; and CAP). Hospitalisation rates were calculated by age group (65
      79, 80+), gender, and year, using the population from the Institute of Statistics
      (ISTAT) census estimates as denominators. RESULTS: A total of 26,239 pneumonia
      events occurred in 24,338 patients residing in the Lazio region, aged 65+ years:
      2257 HCAP, 6775 PNP, and 17,107 CAP. For all subtypes, the proportion of males
      was greater than females. Comorbidity status was more severe in HCAP than in the
      other categories. In-hospital mortality, 30-day mortality, and length of hospital
      stay were twice higher in HCAP than in CAP episodes. The annual incidence rates
      were 0.7, 2.1, and 5.4 episodes per 1000 residents for HCAP, PNP, and CAP,
      respectively. From 2006 to 2008, incidence rates slightly increased for all three
      subtypes. CONCLUSION: Health care databases can be used to give a timely and
      inexpensive picture of the epidemiology of pneumonia. HCAP represents a distinct
      category of pneumonia, with the longest stay, highest mortality, and the greatest
      comorbidity.

PMID- 24274681
TI  - Quantitative studies on roast kinetics for bioactives in coffee.
AB  - Quantitative analysis of the bioactives trigonelline (1), N-methylpyridinium (2),
      caffeine (3), and caffeoylquinic acids (4) in a large set of roasted Arabica
      (total sample size n = 113) and Robusta coffees (total sample size n = 38)
      revealed that the concentrations of 1 and 4 significantly correlated with the
      roasting color (P < 0.001, two tailed), whereas that of 2 significantly
      correlated inversely with the color (P < 0.001, two tailed). As dark-roasted
      coffees were rich in N-methylpyridinium whereas light-roasted coffees were rich
      in trigonelline and caffeoylquinic acids, manufacturing of roast coffees rich in
      all four bioactives would therefore necessitate blending of two or even more
      coffees of different roasting colors. Additional experiments on the migration
      rates during coffee brewing showed that all four bioactives were nearly
      quantitatively extracted in the brew (>90%) when a water volume/coffee powder
      ratio of >16 was used. 

PMID- 24274682
TI  - Region-selective self-assembly of functionalized carbon allotropes from solution.
AB  - Approaches for the selective self-assembly of functionalized carbon allotropes
      from solution are developed and validated for 0D-fullerenes, 1D-carbon nanotubes
      and 2D-graphene. By choosing the right molecular interaction of self-assembled
      monolayers (serving the surface) with the functionalization features of carbon
      materials, which provide the solubility but also serve the driving force for
      assembly, we demonstrate a region-selective and self-terminating assembly of the
      materials. Active layers of the carbon allotropes can be selectively deposited in
      the channel region of thin-film transistor (TFT) devices by this approach. As an
      example for a 0D system, molecules of C60 functionalized octadecylphosphonic
      acids are used to realize self-assembled monolayer field-effect transistors
      (SAMFETs) based on a selective molecular exchange reaction of stearic acid in the
      channel region. For noncovalently functionalized single-walled carbon nanotubes
      (SWCNTs) and graphene oxide (GO) flakes, the electrostatic Coulomb interactions
      between the functional groups of the carbon allotropes and the charged head
      groups of a SAM dielectric layer are utilized to implement the selective
      deposition. 

PMID- 24274683
TI  - Treatment of ovarian lesions in children and adolescents: a retrospective study
      of 130 cases.
AB  - In this study, we analyze the management of ovarian masses in a total of 130
      children surgically treated for 137 ovarian lesions (7 bilateral). The most
      frequent symptoms were chronic (52.3%) and acute (25.4%) abdominal pain.
      Histological examination revealed 64 (46.7%) functional lesions, 59 (43.1%)
      benign neoplasms, 5 (3.7%) malignant ones, and 7 (6.6%) torsed normal ovaries.
      Ovarian torsion occurred in 36 cases (26.27%). A conservative treatment was
      performed in 81 (59.1%) girls: 61 (75.3%) treated in nonemergency and 20 (24.7%)
      in emergency surgery; laparoscopic approach in 35 cases (43.2%); and open surgery
      in 46 (56.8%). The remaining 56 (40.9%) ovarian masses underwent nonconservative
      surgery: 40 cases (71.4%) nonemergency and 16 (28.6%) emergency; laparoscopy in
      20 patients (35.7%); and open surgery in 36 (64.3%). Fertility preservation
      should be a goal in the surgical treatment. The management of ovarian torsion
      should include adnexal detorsion and recovery of the ovarian tissue. In case of
      benign neoplasms, laparoscopic tumorectomy should be the gold standard; in early
      stage malignant tumors, fertility-sparing surgery with accurate staging is
      preferred. 

PMID- 24274684
TI  - Peste des petits ruminants infection among cattle and wildlife in northern
      Tanzania.
AB  - We investigated peste des petits ruminants (PPR) infection in cattle and wildlife
      in northern Tanzania. No wildlife from protected ecosystems were seropositive.
      However, cattle from villages where an outbreak had occurred among small
      ruminants showed high PPR seropositivity, indicating that spillover infection
      affects cattle. Thus, cattle could be of value for PPR serosurveillance. 

PMID- 24274685
TI  - High-resolution hydrodynamic chromatographic separation of large DNA using
      narrow, bare open capillaries: a rapid and economical alternative technology to
      pulsed-field gel electrophoresis?
AB  - A high-resolution, rapid, and economical hydrodynamic chromatographic (HDC)
      method for large DNA separations in free solution was developed using narrow (5
      MUm diameter), bare open capillaries. Size-based separation was achieved in a
      chromatographic format with larger DNA molecules being eluting faster than
      smaller ones. Lambda DNA Mono Cut Mix was baseline-separated with the percentage
      resolutions generally less than 9.0% for all DNA fragments (1.5 to 48.5 kbp)
      tested in this work. High efficiencies were achieved for large DNA from this
      chromatographic technique, and the number of theoretical plates reached 3.6 *
      10(5) plates for the longest (48.5 kbp) and 3.7 * 10(5) plates for the shortest
      (1.5 kbp) fragments. HDC parameters and performances were also discussed. The
      method was further applied for fractionating large DNA fragments from real-world
      samples (SacII digested Arabidopsis plant bacterial artificial chromosome (BAC)
      DNA and PmeI digested Rice BAC DNA) to demonstrate its feasibility for BAC DNA
      finger printing. Rapid separation of PmeI digested Rice BAC DNA covering from
      0.44 to 119.041 kbp was achieved in less than 26 min. All DNA fragments of these
      samples were baseline separated in narrow bare open capillaries, while the
      smallest fragment (0.44 kbp) was missing in pulsed-field gel electrophoresis
      (PFGE) separation mode. It is demonstrated that narrow bare open capillary
      chromatography can realize a rapid separation for a wide size range of DNA
      mixtures that contain both small and large DNA fragments in a single run. 

PMID- 24274686
TI  - Accuracy of self-reported weight and height in women from Bogota, Colombia.
AB  - AIM: To identify correlates of bias in self-reported anthropometry among
      reproductive-aged Colombian women and to correct overweight/obesity and obesity
      prevalence based on self-reported data using two calibration techniques. SUBJECTS
      AND METHODS: Self-reported and objectively measured anthropometry were obtained
      from 597 women aged 21-55 years from Bogota, Colombia. This study identified
      correlates of reporting bias (self-reported minus measured anthropometry) by
      examining its distribution across categories of sociodemographic characteristics,
      objectively measured anthropometry and body shape perception using linear
      regression. Next, weight status misclassification was assessed using self
      reported anthropometry. Finally, multivariable linear regression and ROC curves
      were used to calibrate weight status misclassification from self-reported data;
      these techniques were applied in half of the study population and validated in
      the remaining half. RESULTS: Women under-estimated weight by 2.0 +/- 5.0 kg and
      over-estimated height by 0.6 +/- 4.0 cm. Correlates of bias included objectively
      measured anthropometry and marital status. Self-reported BMI yielded spuriously
      low prevalences of overweight/obesity and obesity. The ROC approach effectively
      corrected overweight/obesity prevalence, while the regression method provided a
      more accurate estimate of obesity prevalence. CONCLUSIONS: Bias in self-reported
      anthropometry varied with respect to objectively measured anthropometry and
      sociodemographic characteristics. BMI from self-reported anthropometry under
      estimates overweight/obesity and obesity prevalence; calibration methods can
      effectively correct reporting bias.

PMID- 24274687
TI  - Multiplex molecular testing for management of infectious gastroenteritis in a
      hospital setting: a comparative diagnostic and clinical utility study.
AB  - Laboratory diagnosis and clinical management of inpatients with diarrhoea is
      complex and time consuming. Tests are often requested sequentially and undertaken
      in different laboratories. This causes prolonged unnecessary presumptive
      isolation of patients, because most cases are non-infectious. A molecular
      multiplex test (Luminex((r)) Gastrointestinal Pathogen Panel (GPP)) was compared
      with conventional testing over 8 months to determine diagnostic accuracy,
      turnaround times, laboratory costs, use of isolation facilities and user
      acceptability. A total of 262 (12%) patients had a pathogen detected by
      conventional methods compared with 483 (22.1%) by GPP. Most additional cases were
      detected in patients developing symptoms in the first 4 days of admission.
      Additional cases were detected because of presumed improved diagnostic
      sensitivity but also because clinicians had not requested the correct pathogen.
      Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite
      investigation (66.5 h) but slower than conventional testing for Clostridium
      difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting
      by clinicians and a consolidated laboratory workflow, reducing the overall number
      of specimens received by the laboratory. A total of 154 isolation days were saved
      at an estimated cost of L30 800. Consumables and labour were estimated at L150
      641 compared with L63 431 for conventional testing. Multiplex molecular testing
      using a panel of targets allowed enhanced detection and a consolidated laboratory
      workflow. This is likely to be of greater benefit to cases that present within
      the first 4 days of hospital admission. 

PMID- 24274688
TI  - Medication adherence in HIV-positive patients with diabetes or hypertension: a
      focus group study.
AB  - BACKGROUND: People with HIV are living longer with potent antiretroviral therapy
      (ART), and HIV is increasingly complicated by other chronic medical
      comorbidities. The objective of this study was to explore HIV-positive patients'
      perspectives on living with HIV and diabetes mellitus (DM) or hypertension (HTN)
      and factors affecting medication adherence. METHODS: We conducted six focus
      groups. Two investigators independently coded transcripts for thematic content
      using editing style analysis. Codes were grouped into conceptual themes using
      consensus process. RESULTS: Thirty-five HIV-positive patients with diabetes or
      hypertension participated. Four major themes emerged: (1) Comorbidities are a
      source of concern and frustration, sometimes eclipsing concern regarding HIV (2)
      Understanding of health conditions and medications promotes adherence, (3)
      Simpler regimens with fewer side effects promote adherence, and (4) Untreated
      substance abuse and mental health issues hinder adherence. CONCLUSIONS: HIV
      positive patients in this study voiced concern regarding medical comorbidities
      and highlighted patient understanding, regimen factors, and substance
      abuse/mental health issues as barriers to adherence. Addressing these issues may
      improve outcomes in the aging HIV-positive population. Adherence to medications
      among HIV-positive patients with DM or HTN may be influenced by providing
      targeted disease-specific education, simplifying regimens, and treatment of
      substance abuse/mental health issues.

PMID- 24274689
TI  - Modulation of quinone PCET reaction by Ca2+ ion captured by calix[4]quinone in
      water.
AB  - Calix[4]arene-triacid-monoquinone (CTAQ), a quinone-containing water-soluble
      ionophore, was utilized to investigate how proton-coupled electron transfer
      (PCET) reactions of quinones were influenced by redox-inactive metal ions in
      aqueous environment. This ionophoric quinone derivative captured a Ca(2+) ion
      that drastically altered the voltammetric behavior of quinone, showing a
      characteristic response to pH and unique redox wave separation.
      Spectroelectrochemistry verified significant stabilization of the semiquinone,
      and electrocatalytic currents were observed in the presence of Ca(2+)-free CTAQ.
      Using digital simulation of cyclic voltammograms to clarify how the thermodynamic
      properties of quinones were altered, a simple scheme was proposed that
      successfully accounted for all the observations. The change induced by Ca(2+)
      complexation was explained on the basis of the combined effects of the
      electrostatic influence of the captured metal ion and hydrogen bonding of water
      molecules with the support of DFT calculation. 

PMID- 24274690
TI  - Mixing and reaction kinetics in porous media: an experimental pore scale
      quantification.
AB  - We propose a new experimental set up to characterize mixing and reactive
      transport in porous media with a high spatial resolution at the pore scale. The
      analogous porous medium consists of a Hele-Shaw cell containing a single layer of
      cylindrical solid grains built by soft lithography. On the one hand, the
      measurement of the local, intrapore, conservative concentration field is done
      using a fluorescent tracer. On the other hand, considering a fast bimolecular
      reaction A + B -> C occurring as A displaces B, we quantify the rate of product
      formation from the spatially resolved measurement of the pore scale reaction
      rate, using a chemiluminescent reaction. The setup provides a dynamical
      measurement of the local concentration field over 3 orders of magnitude and
      allows investigating a wide range of Peclet and Damkohler numbers by varying the
      flow rate within the cell and the local reaction rate. We use it to study the
      kinetics of the reaction front between A and B. While the advection-dispersion
      (Fickian) theory, applied at the continuum scale, predicts a scaling of the
      cumulative mass of product C as MC ? ?t, the experiments exhibit two distinct
      regimes in which the produced mass MC evolves faster than the Fickian behavior.
      In both regimes the front rate of product formation is controlled by the geometry
      of the mixing interface between the reactants. Initially, the invading solute is
      organized in stretched lamellae and the reaction is limited by mass transfer
      across the lamella boundaries. At longer times the front evolves into a second
      regime where lamellae coalesce and form a mixing zone whose temporal evolution
      controls the rate of product formation. In this second regime, the produced mass
      of C is directly proportional to the volume of the mixing zone defined from
      conservative species. This interesting property is indeed verified from a
      comparison of the reactive and conservative data. Hence, for both regimes, the
      direct measurement of the spatial distribution of the pore scale reaction rate
      and conservative component concentration is shown to be crucial to understanding
      the departure from the Fickian scaling as well as quantifying the basic
      mechanisms that govern the mixing and reaction dynamics at the pore scale. 

PMID- 24274691
TI  - Subclassification of upper urinary tract urothelial carcinoma by the neutrophil
      to-lymphocyte ratio (NLR) improves prediction of oncological outcome.
AB  - OBJECTIVE: To examine the potential role of the neutrophil-to-lymphocyte ratio
      (NLR) for subclassification of localised upper urinary tract urothelial carcinoma
      (UUT-UC). PATIENTS AND METHODS: From 2004 to 2010, 234 patients with localised
      UUT-UC underwent radical nephroureterectomy (RNU). NLRs were only obtained under
      afebrile conditions before RNU. Patients that underwent neoadjuvant or adjuvant
      chemotherapy were excluded. The prognostic impact of the NLR was assessed using
      the log-rank test and multivariate analyses. RESULTS: Only advanced pathological
      stage (>T2) and a NLR of >3 were independently associated with metastasis (P <
      0.001 and P = 0.02, respectively) and cancer-specific mortality (P = 0.002 and P
      = 0.006, respectively). The use of a NLR of >3 further identified a poor
      prognostic group, especially in patients with T3 UUT-UC for metastasis-free
      survival and cancer-specific survival (log-rank test, both P < 0.001).
      CONCLUSIONS: For localised UUT-UC, pathological stage and preoperative NLR
      independently predict systemic recurrence and cancer-specific death after RNU.
      Using the NLR for subclassification of T3 UUT-UC seems to further identify a poor
      prognostic group and may help with clinical decisions about treatment
      intervention in clinical practice.

PMID- 24274692
TI  - The prognostic value of glycerol-3-phosphate dehydrogenase 1-like expression in
      head and neck squamous cell carcinoma.
AB  - AIMS: In this study, we sought to determine the prognostic significance of
      glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression in head and neck
      squamous cell carcinoma (HNSCC). METHODS AND RESULTS: The mRNA levels of GPD1L
      were measured in 70 paired HNSCC and corresponding adjacent normal tissues using
      real-time PCR. GPD1L protein levels were evaluated in HNSCC from 135 patients
      using immunohistochemical staining. Correlations were analysed between GPD1L
      levels and local recurrence rate, regional recurrence rate, second primary
      malignancy rate), disease-free survival (DFS) and disease-specific survival
      (DSS). The results of real-time PCR showed that, compared with the paired normal
      tissues, mRNA levels of GPD1L were decreased significantly in HNSCC (P < 0.001).
      Patients whose tumours showed high GPD1L protein expression had a significantly
      better prognosis than those whose tumours showed low expression (61.3% versus
      21.4%, P < 0.001 for DFS; 68% versus 39.3%, P = 0.001 for DSS). High GPD1L
      expression was associated with a lower local recurrence rate than low GPD1L
      expression (P = 0.049). Multivariate survival analysis also showed that GPD1L
      expression was an independent prognostic factor (P = 0.001). CONCLUSIONS: Our
      results indicate that the GPD1L expression is a strong predictor for local
      recurrence and survival in HNSCC.

PMID- 24274693
TI  - Modulation of stem cell adhesion and morphology via facile control over surface
      presentation of cell adhesion molecules.
AB  - To encourage cell adhesion on biomaterial surfaces in a more facile, safe, and
      low-cost fashion, we have demonstrated a noncovalent approach to spatially
      conjugate beta-cyclodextrin (beta-CD) modified peptide sequences onto self
      assembled adamantane-terminated polystyrene-b-poly(ethylene oxide) (PS-PEO-Ada)
      films through inclusion complexing interactions between beta-CDs and adamantane.
      By simply blending various ratios of unmodified PS-PEO with a newly synthesized
      PS-PEO-Ada, we produced PS polymer films that displayed well-organized adamantine
      decorated cylindrical PEO domains with varying average interdomain spacings
      ranging from 29 to 47 nm. The presence of the adamantane moiety at the terminal
      end of the PEO chain permitted rapid, and importantly, oriented attachment of
      beta-CD functionalized peptides onto these surfaces. This one-step process not
      only converted these proven nonadherent PS-PEO surfaces into adherent surfaces,
      but also permitted precisely controlled presentation and surface distribution of
      the conjugated peptides. The utility of these surfaces as cell culture substrates
      was confirmed with human mesenchymal stem cells (hMSCs). We observed that with
      increasing PS-PEO-Ada content in the PEO cylindrical domains, these novel polymer
      films displayed improved cell attachment and spreading, with notable differences
      in hMSC morphology. We further confirmed that this novel PS-PEO-Ada surface
      provides a flexible platform for facile conjugation of mixtures of beta-CDs
      functionalized with different peptides, specifically RGD and IKVAV peptides. The
      cell adhesion and spreading assays on these surfaces indicated that the
      morphologies of hMSCs can be easily manipulated, while no significant changes in
      cell attachment were observed. The lock-and-key peptide conjugation technique
      presented in this work is applicable to any substrate that incorporates a moiety
      capable of forming inclusion complexes with alpha-, beta-, and gamma-CDs,
      providing a facile and flexible method by which to construct peptide-conjugated
      biomaterial substrates for a multitude of applications in fields ranging from
      cell bioprocessing and regenerative medicine to cell-based assays. 

PMID- 24274694
TI  - Should level V be included in lateral neck dissection in treating papillary
      thyroid carcinoma?
AB  - BACKGROUND: The study was designed to explore the regular patterns of level V
      lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC), and to indicate
      whether level V should be included in the management of lateral neck dissection
      when treating PTC. METHODS: This retrospective study consisted of 330 patients
      diagnosed with PTC from January 1994 to July 2009 who underwent an operation that
      included therapeutic lateral neck dissection (levels II to V). The patterns of
      lateral neck LNM were analyzed and the relevant risk factors of level V LNM were
      analyzed with univariate and multivariate analysis, respectively. RESULTS: All
      the patients underwent lateral neck dissection at levels II to V. The predominant
      site of metastasis was level III (247/330 (74.8%)), followed by level IV (233/330
      (70.6%)), and level II (215/330 (65.3%)). Simultaneous multilevel involvement
      (level II, III, and IV) of lymphatic metastases presented in 46.1% (152/330) of
      the cases. Level V showed 28.8% (95/330) of nodal metastasis. Multivariate
      analysis showed that level V LNM was significantly associated with location
      (whole thyroid), gross extrathyroidal extension and simultaneous multilevel
      involvement (level II, III and IV). (P <0.05). CONCLUSIONS: Due to relatively
      high rate of level V involvement and its correlation with location (whole
      thyroid), gross extrathyroidal extension and multilevel involvement, we consider
      that it may be more rational to include level V in the therapeutic lateral neck
      dissection when treating PTC, especially for those who have any one of these
      three independent risk factors.

PMID- 24274696
TI  - Adaptive walks and distribution of beneficial fitness effects.
AB  - We study the adaptation dynamics of a maladapted asexual population on rugged
      fitness landscapes with many local fitness peaks. The distribution of beneficial
      fitness effects is assumed to belong to one of the three extreme value domains,
      viz. Weibull, Gumbel, and Frechet. We work in the strong selection-weak mutation
      regime in which beneficial mutations fix sequentially, and the population
      performs an uphill walk on the fitness landscape until a local fitness peak is
      reached. A striking prediction of our analysis is that the fitness difference
      between successive steps follows a pattern of diminishing returns in the Weibull
      domain and accelerating returns in the Frechet domain, as the initial fitness of
      the population is increased. These trends are found to be robust with respect to
      fitness correlations. We believe that this result can be exploited in experiments
      to determine the extreme value domain of the distribution of beneficial fitness
      effects. Our work here differs significantly from the previous ones that assume
      the selection coefficient to be small. On taking large effect mutations into
      account, we find that the length of the walk shows different qualitative trends
      from those derived using small selection coefficient approximation. 

PMID- 24274697
TI  - Colloidal transfer printing.
AB  - Many fields of research have adopted self-assembly of colloidal spheres as an
      easy and reliable method to produce macroscopic structures with nanoscale
      periodicity. The field of soft lithography in particular has used colloidal self
      assembly to fabricate lithographic masks and templates. We developed a colloidal
      lithography method that uses the colloidal assembly directly to produce
      submicrometer topographic and chemical surface patterns. The method does not
      require any specialized equipment, making it particularly useful in biological
      and chemical laboratories without lithography expertise. The technique involves
      the curing and solvent removal of a self-assembled colloidal crystal from an
      inorganic surface. The result is a triangular array of polymer features with
      submicrometer periodicity that covers square centimeters of surface area. The
      feature size and spacing is easily controlled, and the features serve as reactive
      sites for biomolecule immobilization. 

PMID- 24274698
TI  - Gold catalyzed nickel disilicide formation: a new solid-liquid-solid phase growth
      mechanism.
AB  - The vapor-liquid-solid (VLS) mechanism is the predominate growth mechanism for
      semiconductor nanowires (NWs). We report here a new solid-liquid-solid (SLS)
      growth mechanism of a silicide phase in Si NWs using in situ transmission
      electron microcopy (TEM). The new SLS mechanism is analogous to the VLS one in
      relying on a liquid-mediating growth seed, but it is fundamentally different in
      terms of nucleation and mass transport. In SLS growth of Ni disilicide, the Ni
      atoms are supplied from remote Ni particles by interstitial diffusion through a
      Si NW to the pre-existing Au-Si liquid alloy drop at the tip of the NW. Upon
      supersaturation of both Ni and Si in Au, an octahedral nucleus of Ni disilicide
      (NiSi2) forms at the center of the Au liquid alloy, which thereafter sweeps
      through the Si NW and transforms Si into NiSi2. The dissolution of Si by the Au
      alloy liquid mediating layer proceeds with contact angle oscillation at the
      triple point where Si, oxide of Si, and the Au alloy meet, whereas NiSi2 is grown
      from the liquid mediating layer in an atomic stepwise manner. By using in situ
      quenching experiments, we are able to measure the solubility of Ni and Si in the
      Au-Ni-Si ternary alloy. The Au-catalyzed mechanism can lower the formation
      temperature of NiSi2 by 100  degrees C compared with an all solid state reaction.

PMID- 24274699
TI  - Enzymatic fabrication of protein-decorated gold nanoparticles by the aid of
      artificial peptides with gold-binding affinity.
AB  - Here, we report a new approach for the biofabrication of protein-immobilized gold
      nanoparticles (Au NPs), using oxidoreductase with gold-binding peptide-tagged
      recombinant proteins. The reduction of Au ions to Au(0) was achieved using a
      natural electron-donating cofactor, nicotinamide adenine dinucleotide, which was
      regenerated by the glycerol dehydrogenase (GLD) enzyme. First, we selected the A3
      peptide (AYSSGAPPMPPF) as a gold binding moiety. The A3 peptide was introduced to
      the C-terminus of fusion proteins of immunoglobulin G (IgG)-binding domains of
      protein G and protein A. In the presence of the recombinant protein, the GLD
      catalyzed cofactor reduction resulted in the efficient in situ fabrication of Au
      NPs immobilized with the fusion protein. Moreover, the protein-immobilized Au NPs
      were shown to have IgG binding activity. Although the A3 peptide had the ability
      to stabilize Au NPs, the results suggested that its binding affinity for Au NPs
      was unexpectedly weaker than that of His-tag. A cysteine residue was thus
      introduced to a recombinant protein adjacent to the A3 peptide. Finally, an
      artificial peptide, comprising A3 sequence with the C-terminal single cysteine
      residue, enabled the stable display of a fusion protein while maintaining its IgG
      binding activity through the Au-S bond. This enzyme-assisted one-pot methodology
      for protein-Au NPs conjugation offers one potent route for the facile fabrication
      of biomolecule-decorated metal NPs. 

PMID- 24274700
TI  - Surveillance for avian influenza A(H7N9), Beijing, China, 2013.
AB  - During surveillance for pneumonia of unknown etiology and sentinel hospital-based
      surveillance in Beijing, China, we detected avian influenza A(H7N9) virus
      infection in 4 persons who had pneumonia, influenza-like illness, or asymptomatic
      infections. Samples from poultry workers, associated poultry environments, and
      wild birds suggest that this virus might not be present in Beijing. 

PMID- 24274701
TI  - Superresolution localization methods.
AB  - Superresolution localization microscopy methods produce nanoscale images via a
      combination of intermittently active fluorescent probes and algorithms that can
      precisely determine the positions of these probes from single-molecule or few
      molecule images. These algorithms vary widely in their underlying principles,
      complexity, and accuracy. In this review, we begin by surveying the principles of
      localization microscopy and describing the fundamental limits to localization
      precision. We then examine several different families of fluorophore localization
      algorithms, comparing their complexity, performance, and range of applicability
      (e.g., whether they require particular types of experimental information, are
      optimized for specific situations, or are more general). Whereas our focus is on
      the localization of single isotropic emitters in two dimensions, we also consider
      oriented dipoles, three-dimensional localization, and algorithms that can handle
      overlapping images of several nearby fluorophores. Throughout the review, we try
      to highlight practical advice for users of fluorophore localization algorithms,
      as well as open questions. 

PMID- 24274702
TI  - Nitrogen-vacancy centers in diamond: nanoscale sensors for physics and biology.
AB  - Crystal defects in diamond have emerged as unique objects for a variety of
      applications, both because they are very stable and because they have interesting
      optical properties. Embedded in nanocrystals, they can serve, for example, as
      robust single-photon sources or as fluorescent biomarkers of unlimited
      photostability and low cytotoxicity. The most fascinating aspect, however, is the
      ability of some crystal defects, most prominently the nitrogen-vacancy (NV)
      center, to locally detect and measure a number of physical quantities, such as
      magnetic and electric fields. This metrology capacity is based on the quantum
      mechanical interactions of the defect's spin state. In this review, we introduce
      the new and rapidly evolving field of nanoscale sensing based on single NV
      centers in diamond. We give a concise overview of the basic properties of
      diamond, from synthesis to electronic and magnetic properties of embedded NV
      centers. We describe in detail how single NV centers can be harnessed for
      nanoscale sensing, including the physical quantities that may be detected,
      expected sensitivities, and the most common measurement protocols. We conclude by
      highlighting a number of the diverse and exciting applications that may be
      enabled by these novel sensors, ranging from measurements of ion concentrations
      and membrane potentials to nanoscale thermometry and single-spin nuclear magnetic
      resonance. 

PMID- 24274703
TI  - Motion artifact on computed tomography scan suggesting an unstable 3-column spine
      injury: case report of a "near miss" root cause of unneeded surgery.
AB  - BACKGROUND: Polytrauma patients often present with altered mental status, thus
      making clinical examination challenging. Due to its reliability for detecting
      traumatic injuries to the spine, computed tomography (CT) is generally the
      imaging study of choice when the mechanism of injury and/or preliminary exam
      suggests spinal injury. However, motion artifact may lead to false diagnoses.
      CASE REPORT: A 19-year-old intoxicated female involved in a high-speed motor
      vehicle crash suffered multiple spine, head, chest, and abdominal injuries. CT
      scan also suggested an unstable three column ligamentous injury at L2-3.
      Preparations were made for surgery the following morning, by which time her
      mental status had improved. She was re-examined in the operating room prior to
      induction by anesthesia and no focal lumbar pain or tenderness was detected.
      Imaging was further reviewed and motion artifact at the L2-3 level was noted. The
      surgery was cancelled. CONCLUSION: Motion artifact mimicked an unstable three
      column ligamentous injury at the L2-3 level. Findings on CT scan should always be
      correlated to physical exam in order to avoid wrongful surgical intervention.

PMID- 24274704
TI  - Vitamin D-responsive SGPP2 variants associated with lung cell expression and lung
      function.
AB  - BACKGROUND: Vitamin D is associated with lung health in epidemiologic studies,
      but mechanisms mediating observed associations are poorly understood. This study
      explores mechanisms for an effect of vitamin D in lung through an in vivo gene
      expression study, an expression quantitative trait loci (eQTL) analysis in lung
      tissue, and a population-based cohort study of sequence variants. METHODS:
      Microarray analysis investigated the association of gene expression in small
      airway epithelial cells with serum 25(OH)D in adult non-smokers. Sequence
      variants in candidate genes identified by the microarray were investigated in a
      lung tissue eQTL database, and also in relation to cross-sectional pulmonary
      function in the Health, Aging, and Body Composition (Health ABC) study,
      stratified by race, with replication in the Framingham Heart Study (FHS).
      RESULTS: 13 candidate genes had significant differences in expression by serum
      25(OH)D (nominal p < 0.05), and a genome-wide significant eQTL association was
      detected for SGPP2. In Health ABC, SGPP2 SNPs were associated with FEV1 in both
      European- and African-Americans, and the gene-level association was replicated in
      European-American FHS participants. SNPs in 5 additional candidate genes (DAPK1,
      FSTL1, KAL1, KCNS3, and RSAD2) were associated with FEV1 in Health ABC
      participants. CONCLUSIONS: SGPP2, a sphingosine-1-phosphate phosphatase, is a
      novel vitamin D-responsive gene associated with lung function. The identified
      associations will need to be followed up in further studies.

PMID- 24274705
TI  - Solution-based carbohydrate synthesis of individual solid, hollow, and porous
      carbon nanospheres using spray pyrolysis.
AB  - A facile and scalable solution-based, spray pyrolysis synthesis technique was
      used to synthesize individual carbon nanospheres with specific surface area (SSA)
      up to 1106 m(2)/g using a novel metal-salt catalyzed reaction. The carbon
      nanosphere diameters were tunable from 10 nm to several micrometers by varying
      the precursor concentrations. Solid, hollow, and porous carbon nanospheres were
      achieved by simply varying the ratio of catalyst and carbon source without using
      any templates. These hollow carbon nanospheres showed adsorption of to 300 mg of
      dye per gram of carbon, which is more than 15 times higher than that observed for
      conventional carbon black particles. When evaluated as supercapacitor electrode
      materials, specific capacitances of up to 112 F/g at a current density of 0.1 A/g
      were observed, with no capacitance loss after 20,000 cycles.

PMID- 24274706
TI  - Metformin nephrotoxicity insights: will they change clinical management?

PMID- 24274707
TI  - Traditional medicine policy and regulation in Nigeria: an index of herbal
      medicine safety.
AB  - BACKGROUND: The requirements and methods for research and evaluation of the
      safety and efficacy of herbal medicines are more complex than those for
      conventional pharmaceuticals. In addition to the aforementioned and contrary to
      the general belief that herbal medicines are safe and despite the profound
      therapeutic advantages possessed by medicinal plants, some of their constituents
      have been shown to be potentially toxic, carcinogenic, mutagenic, and
      teratogenic. Thus, traditional medicine policy and regulation have been made an
      integral part of the WHO proposed critical determinants of herbal medicine
      safety. OBJECTIVE: Therefore, this study is designed to assess the policy and
      regulation guiding herbal medicine in Nigeria as this information may form a
      safety index of herbal medicine use in Nigeria. METHODOLOGY: Structured
      questionnaire adopted from WHO was used to obtain the opinions of relevant
      stakeholders in the field of herbal medicine on the policy and regulation of
      herbal medicine in Nigeria. RESULTS: The results show that 68.8% of respondents
      agreed that there is a national policy on TM with 31.2% disagreeing on this
      issue. 75% of respondents agreed that implementation of the manufacturing
      requirements of herbal medicines is ensured by control mechanisms while 25%
      disagreed. Only 25% said herbal medicines are sold by licensed practitioners,
      with 75% believing that herbal medicines are sold by non-licensed practitioners.
      87.5% said support from the WHO is needed and should be in the form of workshops
      on national capacity building on safety monitoring of herbal medicines.
      CONCLUSION: There is need for the Federal Ministry of Health to harmonize the
      varying opinions on traditional medicine and policy as documented in this study
      through collaboration and workshops on traditional medicine. These proposed
      approaches may guarantee the safety and regulation of herbal medicine use in
      Nigeria.

PMID- 24274708
TI  - First insights into the molecular epidemiology of tuberculosis in Croatia during
      a three-year period, 2009 to 2011.
AB  - BACKGROUND: Mycobacterium tuberculosis still represents a serious cause of
      morbidity and mortality worldwide. The aim of this study was to determine the
      transmission rate and genetic lineages of M. tuberculosis circulating in Croatia
      during a 3-y period, between 2009 and 2011. METHODS: A total of 1587 M.
      tuberculosis strains (1 strain per tuberculosis patient) isolated in Croatia from
      2009 to 2011 were genotyped using 15-locus mycobacterial interspersed repetitive
      units-variable number of tandem repeats (MIRU-VNTR) analysis. RESULTS: The
      majority of tested isolates (66.73%) belonged to the Euro-American global
      lineage. The most prevalent sub-lineages were Haarlem (48.64%), followed by S
      (6.05%), Cameroon (3.72%), and Latin American-Mediterranean (3.4%). Among the
      total 1587 tested isolates, 996 (63%) were included in 1 of 236 clusters. The
      cluster size ranged from 2 (114 clusters) to 45 (1 cluster) patients, the mean
      cluster size being 4.2. These results indicate that 47.83% of tuberculosis cases
      during the period analyzed were the result of recent transmission. CONCLUSIONS:
      The most prevalent global lineage in Croatia is Euro-American (sub-lineages
      Haarlem, S, Cameroon, and Latin American-Mediterranean). The high clustering rate
      and high medium clustering size of 4.2 tuberculosis cases could indicate a
      possible failure in interrupting the transmission of infection and points to the
      need for improvements in national and local tuberculosis control activities. This
      is the first study describing the molecular epidemiology of tuberculosis in
      Croatia.

PMID- 24274709
TI  - Predicted cardiovascular risk in HIV-infected patients.

PMID- 24274710
TI  - Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian
      population.
AB  - Lipoarabinomannan (LAM), a cell wall component of mycobacteria, can be detected
      in the urine of tuberculosis (TB) patients. Advantages of this diagnostic include
      the ease of sample collection and test methods. However, as with most new TB
      diagnostics, LAM tests have been evaluated in well-controlled laboratory settings
      and subsequently need assessment under real working conditions. Our experience
      showed that the diagnosis of TB using the detection of LAM in urine under field
      conditions is prone to false-positive results due to contamination. Dust and
      soil, but also stool, seemed to lead to increased OD values and thus false
      positive results of the enzyme-linked immunosorbent assay (ELISA) for LAM;
      however, contamination with blood, as well as bacterial or fungal organisms, had
      no influence. The collection of urine for the detection of LAM should therefore
      follow strict collection criteria in order to avoid contamination.

PMID- 24274711
TI  - Antiviral susceptibility of highly pathogenic avian influenza A(H5N1) viruses
      isolated from poultry, Vietnam, 2009-2011.
AB  - We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated
      from poultry in Vietnam during 2009-2011. Of 25 clade 1.1 viruses, all possessed
      a marker of resistance to M2 blockers amantadine and rimantadine; 24 were
      inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W
      neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and
      laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses
      contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir.
      One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance
      and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral
      agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK
      SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that
      of wildtype virus. These findings highlight the role of drug susceptibility
      monitoring of H5N1 subtype viruses circulating among birds to inform antiviral
      stockpiling decisions for pandemic preparedness. 

PMID- 24274712
TI  - Plant biomass recalcitrance: effect of hemicellulose composition on nanoscale
      forces that control cell wall strength.
AB  - Efficient conversion of lignocellulosic biomass to second-generation biofuels and
      valuable chemicals requires decomposition of resilient plant cell wall structure.
      Cell wall recalcitrance varies among plant species and even phenotypes, depending
      on the chemical composition of the noncellulosic matrix. Changing the amount and
      composition of branches attached to the hemicellulose backbone can significantly
      alter the cell wall strength and microstructure. We address the effect of
      hemicellulose composition on primary cell wall assembly forces by using the 3D
      RISM-KH molecular theory of solvation, which provides statistical-mechanical
      sampling and molecular picture of hemicellulose arrangement around cellulose. We
      show that hemicellulose branches of arabinose, glucuronic acid, and especially
      glucuronate strengthen the primary cell wall by strongly coordinating to hydrogen
      bond donor sites on the cellulose surface. We reveal molecular forces maintaining
      the cell wall structure and provide directions for genetic modulation of plants
      and pretreatment design to render biomass more amenable to processing. 

PMID- 24274713
TI  - Oxidative CO2 reforming of methane in La0.6Sr0.4Co0.8Ga0.2O3-delta (LSCG) hollow
      fiber membrane reactor.
AB  - CO2 utilization in catalytic membrane reactors for syngas production is an
      environmentally benign solution to counter the escalating global CO2 concerns. In
      this study, integration of a La0.6Sr0.4Co0.8Ga0.2O3-delta (LSCG) hollow fiber
      membrane reactor with Ni/LaAlO3-Al2O3 catalyst for the oxidative CO2 reforming of
      methane (OCRM) reaction was successfully tested for 160 h of reaction. High CH4
      and CO2 conversions of ca. 94% and 73% were obtained with O2 flux ca. 1 mL.min(
      1).cm(-2) at 725  degrees C for the 160-h stability test. Surface temperature
      programmed desorption studies of the membrane were conducted with H2, CO, and CO2
      as probe gases to facilitate understanding on the effect of H2 and CO product
      gases as well as CO2 reactant gases on the membrane surface. Scanning electron
      microscopy-energy dispersive X-ray (SEM-EDX), X-ray photoelectron spectroscopy
      (XPS), and Fourier transform infrared (FTIR) analysis of the postreacted membrane
      after 160-h stability tests suggests Sr-enriched phases with the presence of
      adsorbed carbonate and hydrogenated carbon. This shows the subsequent reactant
      spillover on the membrane surface from the catalyst bed took place due to the
      reaction occurring on the catalyst. However, XRD analysis of the bulk structure
      does not show any phase impurities, thus confirming the structural integrity of
      the LSCG hollow fiber membrane. 

PMID- 24274714
TI  - Pleomorphic liposarcoma: a clinicopathological, immunohistochemical and molecular
      cytogenetic study of 32 additional cases.
AB  - The purpose of this study is to report the author's experience with 32 cases of
      pleomorphic liposarcoma to further broaden the clinicopathological spectrum. The
      tumours occurred equally in males and females with ages ranging from 11 to 83
      years (median, 56 years). Tumour site included the extremities (17 cases),
      abdomen/retroperitoneum (4 cases), internal organs (5 cases), thoracic
      cavity/mediastinum (2 cases), orbit, neck, groin and scrotum (1 case each). The
      diagnostic pleomorphic lipoblasts were identified in 31 primary tumours and one
      recurrent tumor but varied widely in proportion between cases or different areas
      of the same tumor. Four tumors contained sheets or focal aggregates of lipoblasts
      with epithelioid morphology. The nonlipogenic component in 26 cases had an
      appearance of undifferentiated pleomorphic sarcoma, whereas in six cases it was
      consistent with intermediate to high grade myxofibrosarcoma. The pleormorphic and
      epithelioid lipoblasts displayed variable expression of S100 protein. There was
      no signal of amplified MDM2 gene in 10 cases tested by fluorescence in situ
      hybridization. This study further illustrates that pleomorphic liposarcoma is a
      distinctive entity with no relationship to either well differentiated liposarcoma
      or dedifferentiated liposarcoma. Albeit very rare, pleomorphic liposarcoma can
      occur in teenaged patients and internal organs. 

PMID- 24274715
TI  - Elevated Ki-67 labeling index in 'synchronous liver metastases' of well
      differentiated enteropancreatic neuroendocrine tumor.
AB  - There is no consensus as to whether or not metastatic nodules in the liver should
      be biopsied for tumor grading in cases of neuroendocrine tumors with 'synchronous
      liver metastasis'. In this study, we compared the Ki-67 labeling index between
      the primary tumor and synchronous liver metastasis in 30 patients, who had
      received simultaneous resections. Examined tumors were of the small bowel (n =
      18) or pancreas (n = 12), and G1 or G2 in primary histologic grade. In 20
      patients (67%), the Ki-67 index was similar between the primary tumor and liver
      metastasis, but 10 (33%) showed an elevation of 3.4-14.4% in the liver, which
      increased the tumor grade in 4 cases. The Ki-67 elevation in the liver was more
      common in G2 than G1 neoplasms (P = 0.002). The size, but not number, of liver
      metastases was significantly larger in patients with an elevated Ki-67 index (P =
      0.006). Using 40 mm as a provisional cutoff for the greatest diameter of liver
      metastases, the positive predictive value of this discriminator for elevated Ki
      67 was 56%, and the negative predictive value was 93%. In conclusion, synchronous
      liver metastases can yield a higher Ki-67 labeling index than primary
      neuroendocrine tumours, particularly when the secondary is greater than 40 mm. 

PMID- 24274716
TI  - Histological assessment of intra- and inter-institutional reliabilities in
      detection of desmoplastic reaction in biopsy specimens of early colorectal
      carcinomas.
AB  - We previously reported a relationship between depth of submucosal invasion of
      early colorectal carcinomas and desmoplastic reaction (DR). However, poor inter
      observer agreement on the histopathological diagnosis of DR in biopsy specimens
      with hematoxylin and eosin (H&E) staining has been the major critique of this
      tool. In this study, reproducibility of the histopathological diagnosis of DR was
      evaluated. Furthermore, we investigated the possible improvement of the
      reproducibility after education about histological characteristics and tried to
      identify histological characteristics that are most important in the recognition
      of DR. A total of 34 H&E stained slides were included in this study and analyzed
      by three pathologists. Slides were reviewed before and after education about
      histological characteristics of DR. Kappa statistics were used to compare the
      inter-observer variability. We investigated the relationship between DR and
      histopathological factor. The inter-observer agreement during the first session
      varied between 0.30 and 0.63, which improved during the second session toward an
      agreement between 0.58 and 0.71. Myofibroblast proliferation associated with
      cancer invasion was found to be the most useful in the diagnosis of DR. In
      conclusion, the correct detection of myofibroblasts may facilitate the
      standardization of diagnosis of DR. 

PMID- 24274717
TI  - Fatty acid binding protein 7 as a marker of glioma stem cells.
AB  - Glioblastomas are the most aggressive brain tumors. Glioblastoma stem cells
      (GSCs) are thought to be responsible for the recurrence, chemoresistance, and
      poor prognosis of glioblastoma. Fatty acid binding protein 7 (FABP7), which is a
      cellular chaperone for a variety of omega-3 fatty acids, is a known marker for
      neural stem cells. In this study, using a newly developed anti-FABP7 antibody and
      patient-derived GSC lines, we evaluated the expression of FABP7 in GSCs. Using
      immunocytochemistry, Western blotting, and qPCR analyses, FABP7 was found to be
      highly enriched in GSCs and its localization was found in cytosol and nuclei.
      FABP7 expression was significantly downregulated in differentiated GSCs induced
      by the addition of serum. In the glioma surgical specimens, FABP7 was highly
      expressed in the majority of glioblastoma. Double immunostaining for FABP7 and
      Sox2 showed that FABP7(+) Sox2(+) tumor cells were significantly increased in
      glioblastoma (grade IV) compared with diffuse astrocytoma (grade II) and
      anaplastic astrocytoma (grade III). Our data introduces FABP7 as a marker for
      GSCs and further highlights its possible significance for glioma diagnosis and
      treatment. 

PMID- 24274718
TI  - Plexiform fibrohistiocytic tumor of bone.
AB  - Plexiform fibrohistiocytic tumor is an extremely rare soft tissue tumor with a
      low malignancy potential. The patient is usually a child or a young adolescent
      and the tumor is usually localized in the upper extremities. We report on a case
      of a 21-year old male with a plexiform fibrohistiocytic tumor in the left fibula
      admitted to our hospital due to a swelling and pain in the left lower extremity.
      Radiologically a lytic lesion in the distal end of left fibula consistent with a
      non-aggressive lesion with low biological activity was found. Treated with
      curettage, the specimen revealed plexiform proliferation of mononuclear
      histiocyte-like cells, multinucleated osteoclast-like cells, and spindle
      fibroblast-like cells in variable proportions histopathologically.
      Immunohistochemical stains were positive for CD68 in scattered fashion in
      histiocytes and giant cells, and spindle like cells showed positivity for smooth
      muscle actin. Under electron microscopy, rough endoplasmic reticulum and collagen
      bundles in the spindle cells suggested fibroblastic differentiation. Also
      multiple large electron-dense lysosomal granules in histiocytoid cells were
      found. Multinucleated giant cells exhibited osteoclast-like appearance. All these
      findings suggested plexiform fibrohistiocytic tumor. Interestingly, the tumor was
      localized in bone. During the follow up for 27 months after the resection, there
      was no recurrence or metastasis. 

PMID- 24274719
TI  - Is it a primary or metastatic melanocytic neoplasm of the central nervous
      system?: A molecular based approach.
AB  - Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon
      and must be distinguished from metastatic lesions as patients with metastatic
      disease carry a worse prognosis. Therefore, tools to aid in the diagnosis of a
      primary CNS melanocytic neoplasm would be of clinical utility. Primary CNS
      melanocytic neoplasms, including uveal melanomas have frequent mutations in GNAQ
      and GNA11, but are rare in cutaneous and mucosal melanomas. Additionally, primary
      uveal melanomas often exhibit monosomy 3 conferring an elevated risk of
      metastasis. We present a 63 year-old male with a melanocytic neoplasm in the
      thoracic spinal cord. Molecular studies revealed the tumor contained a GNAQ
      mutation and four-color fluorescent in situ hybridization (FISH) composed of
      chromosome enumeration probes for 3, 7, 17 and a locus specific probe for
      9p21/CDKN2A yielded a normal result (i.e. two copies per cell), favoring a
      primary versus metastatic melanocytic neoplasm of the CNS. We report a case in
      which the combination of mutational analysis and FISH aided in identifying the
      origin of the neoplasm. 

PMID- 24274720
TI  - Russell body gastritis showing IgM kappa-type monoclonality.

PMID- 24274721
TI  - TCRgamma rearrangement and Epstein- Barr virus are detected both in
      lymphadenopathy of adult-onset Still's disease and in accompanying peripheral T
      cell lymphoma.

PMID- 24274722
TI  - Neoadjuvant chemotherapy for bladder cancer does not increase risk of
      perioperative morbidity.
AB  - OBJECTIVE: To determine whether neoadjuvant chemotherapy (NAC) is a predictor of
      postoperative complications, length of stay (LOS), or operating time after
      radical cystectomy (RC) for bladder cancer. PATIENTS AND METHODS: A retrospective
      review of the American College of Surgeons National Surgical Quality Improvement
      Program (NSQIP) database was performed to identify patients receiving NAC before
      RC from 2005 to 2011. Bivariable and multivariable analyses were used to
      determine whether NAC was associated with 30-day perioperative outcomes, e.g.
      complications, LOS, and operating time. RESULTS: Of the 878 patients who
      underwent RC for bladder cancer in our study, 78 (8.9%) received NAC. Excluding
      those patients who were ineligible for NAC due to renal insufficiency, 78/642
      (12.1%) received NAC. In all, 457 of the 878 patients (52.1%) undergoing RC had
      at least one complication <=30 days of RC, including 43 of 78 patients (55.1%)
      who received NAC and 414 of 800 patients (51.8%) who did not (P = 0.58). On
      multivariable logistic regression, NAC was not a predictor of complications (P =
      0.87), re-operation (P = 0.16), wound infection (P = 0.32), or wound dehiscence
      (P = 0.32). Using multiple linear regression, NAC was not a predictor of
      increased operating time (P = 0.24), and patients undergoing NAC had a decreased
      LOS (P = 0.02). CONCLUSIONS: Our study is the first large multi-institutional
      analysis specifically comparing complications after RC with and without NAC.
      Using a nationally validated, prospectively maintained database specifically
      designed to measure perioperative outcomes, we found no increase in perioperative
      complications or surgical morbidity with NAC. Considering these findings and the
      well-established overall survival benefit over surgery alone, efforts are needed
      to improve the uptake of NAC.

PMID- 24274723
TI  - Simplifying antiretroviral therapy to lopinavir/ritonavir monotherapy did not
      improve quality of life and therapy adherence in pretreated HIV-infected
      children.
AB  - We reported quality of life (QOL) and adherence in HIV-infected children after
      simplifying the antiretroviral regimen by switching to lopinavir/ritonavir
      monotherapy (mLPV/r). HIV-infected children with HIV-RNA <50 copies/ml while
      using second-line double boosted protease inhibitors were switched to mLPV/r.
      Primary caregivers completed PACTG QOL questionnaires at weeks 0, 48, 96, and
      144. Adherence by pill count was performed at every visit. Thirty-eight
      pretreated HIV-infected Thai children were enrolled. The median (IQR) age was
      11.5 (10.2-13.2) years and 53% were female. At enrollment, 34 used
      LPV/r+saquinavir and four used LPV/r+indinavir. The median (IQR) CD4% was 27 (23
      30)%. At week 144, QOL scores were similar to baseline for all domains. A
      transient increase in the symptoms domain score was seen at week 96 (p=0.01),
      whereas the physical resilience domain score was decreased at weeks 48 and 96
      (both p<0.05). Despite the mean number of pills decreasing from 7.9 pills/day
      before and 3.7 pills/day after mLPV/r (p<0.001), there were no differences over
      time in adherence rates by pill count and proportion of children with poor
      adherence (all p>0.05). Our study did not demonstrate improvement of QOL scores
      and adherence rates by pill count in pretreated HIV-infected children after
      simplification of the antiretroviral regimen to lopinavir/ritonavir monotherapy.

PMID- 24274724
TI  - Changes in chokeberry (Aronia melanocarpa L.) polyphenols during juice processing
      and storage.
AB  - Chokeberries are an excellent source of polyphenols, but their fate during juice
      processing and storage is unknown. The stability of anthocyanins, total
      proanthocyanidins, hydroxycinnamic acids, and flavonols at various stages of
      juice processing and over 6 months of storage at 25  degrees C was determined.
      Flavonols, total proanthocyanidins, and hydroxycinnamic acids were retained in
      the juice to a greater extent than anthocyanins, with losses mostly due to
      removal of seeds and skins following pressing. Anthocyanins were extensively
      degraded by thermal treatments during which time levels of protocatechuic acid
      and phloroglucinaldehyde increased, and additional losses occurred following
      pressing. Flavonols, total proanthocyanidins, and hydroxycinnamic acids were well
      retained in juices stored for 6 months at 25  degrees C, whereas anthocyanins
      declined linearly. Anthocyanin losses during storage were paralleled by increased
      polymeric color values, indicating that the small amounts of anthocyanins
      remaining were present in large part in polymeric forms. 

PMID- 24274725
TI  - Isotopic ratio outlier analysis global metabolomics of Caenorhabditis elegans.
AB  - We demonstrate the global metabolic analysis of Caenorhabditis elegans stress
      responses using a mass-spectrometry-based technique called isotopic ratio outlier
      analysis (IROA). In an IROA protocol, control and experimental samples are
      isotopically labeled with 95 and 5% (13)C, and the two sample populations are
      mixed together for uniform extraction, sample preparation, and LC-MS analysis.
      This labeling strategy provides several advantages over conventional approaches:
      (1) compounds arising from biosynthesis are easily distinguished from artifacts,
      (2) errors from sample extraction and preparation are minimized because the
      control and experiment are combined into a single sample, (3) measurement of both
      the molecular weight and the exact number of carbon atoms in each molecule
      provides extremely accurate molecular formulas, and (4) relative concentrations
      of all metabolites are easily determined. A heat-shock perturbation was conducted
      on C. elegans to demonstrate this approach. We identified many compounds that
      significantly changed upon heat shock, including several from the purine
      metabolism pathway. The metabolomic response information by IROA may be
      interpreted in the context of a wealth of genetic and proteomic information
      available for C. elegans . Furthermore, the IROA protocol can be applied to any
      organism that can be isotopically labeled, making it a powerful new tool in a
      global metabolomics pipeline. 

PMID- 24274726
TI  - From "Sooo excited!!!" to "So proud": using language to study development.
AB  - We introduce a new method, differential language analysis (DLA), for studying
      human development in which computational linguistics are used to analyze the big
      data available through online social media in light of psychological theory. Our
      open vocabulary DLA approach finds words, phrases, and topics that distinguish
      groups of people based on 1 or more characteristics. Using a data set of over
      70,000 Facebook users, we identify how word and topic use vary as a function of
      age and compile cohort specific words and phrases into visual summaries that are
      face valid and intuitively meaningful. We demonstrate how this methodology can be
      used to test developmental hypotheses, using the aging positivity effect
      (Carstensen & Mikels, 2005) as an example. While in this study we focused
      primarily on common trends across age-related cohorts, the same methodology can
      be used to explore heterogeneity within developmental stages or to explore other
      characteristics that differentiate groups of people. Our comprehensive list of
      words and topics is available on our web site for deeper exploration by the
      research community.

PMID- 24274727
TI  - Pink frilly dresses and the avoidance of all things "girly": children's
      appearance rigidity and cognitive theories of gender development.
AB  - Many young children pass through a stage of gender appearance rigidity; girls
      insist on wearing dresses, often pink and frilly, whereas boys refuse to wear
      anything with a hint of femininity. In 2 studies, we investigated the prevalence
      of this apparent hallmark of early gender development and its relation to
      children's growing identification with a gender category. Study 1a examined the
      prevalence of this behavior and whether it would exhibit a developmental pattern
      of rigidity followed by flexibility, consistent with past research on identity
      related cognitions. Interviews with 76 White, middle-class parents and their 3-
      to 6-year-old children revealed that about two thirds of parents of 3- and 4-year
      old girls and almost half (44%) of parents of 5- and 6-year-old boys reported
      that their children had exhibited a period of rigidity in their gender-related
      appearance behavior. Appearance rigidity was not related to parents' preferences
      for their children's gender-typed clothing. Study 1b examined whether cognitive
      theories of identity development could shed light on gender appearance rigidity.
      The more important and positive children considered their gender and the more
      children understood that gender categories remain stable over time (gender
      stability), the more likely children were to wear gender-typed outfits. In Study
      2, we extended this research to a more diverse population and found that gender
      appearance rigidity was also prevalent in 267 4-year-old children in the United
      States from African American, Chinese, Dominican, and Mexican immigrant low
      income backgrounds. Results suggest that rigid gender-related appearance behavior
      can be seen among young children from different backgrounds and might reflect
      early developing cognitions about gender identity.

PMID- 24274728
TI  - Influence of conduct problems and depressive symptomatology on adolescent
      substance use: developmentally proximal versus distal effects.
AB  - The identification of developmentally specific windows at which key predictors of
      adolescent substance use are most influential is a crucial task for informing the
      design of appropriately targeted substance use prevention and intervention
      programs. The current study examined effects of conduct problems and depressive
      symptomatology on changes in alcohol, cigarette, and marijuana from 8th through
      12th grade. We examined the effects of relatively developmentally distal versus
      proximal mental health problems on adolescent substance use and tested for gender
      differences. With a national, longitudinal sample from the Monitoring the Future
      study (N = 3,014), structural equation modeling was used to test the effects of
      8th and 10th grade conduct problems and depressive symptomatology on subsequent
      changes in alcohol, cigarette, and marijuana use from 8th through 12th grade.
      Results indicated that relatively distal (8th grade) mental health problems were
      stronger predictors of increases in alcohol, cigarette, and marijuana use than
      were relatively more proximal (10th grade) mental health problems. Eighth grade
      conduct problems had the strongest effects on alcohol and marijuana use, and 8th
      grade depressive symptomatology had the strongest effects on cigarette use. Few
      gender differences were observed. These results suggest that intervening in
      earlier appearing conduct problems and depressive symptomatology may lead to a
      reduction in adolescent substance use in 10th and 12th grades and beyond.

PMID- 24274729
TI  - Interfacial protein-protein associations.
AB  - While traditional models of protein adsorption focus primarily on direct protein
      surface interactions, recent findings suggest that protein-protein interactions
      may play a central role. Using high-throughput intermolecular resonance energy
      transfer (RET) tracking, we directly observed dynamic, protein-protein
      associations of bovine serum albumin on polyethylene glycol modified surfaces.
      The associations were heterogeneous and reversible, and associating molecules
      resided on the surface for longer times. The appearance of three distinct RET
      states suggested a spatially heterogeneous surface - with areas of high protein
      density (i.e., strongly interacting clusters) coexisting with mobile monomers.
      Distinct association states exhibited characteristic behavior, i.e., partial-RET
      (monomer-monomer) associations were shorter-lived than complete-RET (protein
      cluster) associations. While the fractional surface area covered by regions with
      high protein density (i.e., clusters) increased with increasing concentration,
      the distribution of contact times between monomers and clusters was independent
      of solution concentration, suggesting that associations were a local phenomenon,
      and independent of the global surface coverage. 

PMID- 24274730
TI  - Reduced fatalism and increased prevention behavior after two high-profile lung
      cancer events.
AB  - The positive impact of media coverage of high-profile cancer events on cancer
      prevention behaviors is well-established. However, less work has focused on
      potential adverse psychological reactions to such events, such as fatalism.
      Conducting 3 studies, the authors explored how the lung cancer death of Peter
      Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a
      national media sample in Study 1 found that media coverage of these events often
      focused on reiterating the typical profile of those diagnosed with lung cancer;
      38% of the media mentioned at least 1 known risk factor for lung cancer, most
      often smoking. Data from a nationally representative survey in Study 2 found that
      respondents reported lower lung cancer fatalism, after, compared with before, the
      events (OR = 0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to
      the national tobacco Quitline after these events was found in Study 3. These
      results suggest that there is a temporal association between high-profile cancer
      events, the subsequent media coverage, psychological outcomes, and cancer
      prevention behaviors. These results suggest that high-profile cancer events could
      be leveraged as an opportunity for large-scale public heath communication
      campaigns through the dissemination of cancer prevention messages and services. 

PMID- 24274731
TI  - Side-chain amino-acid-based pH-responsive self-assembled block copolymers for
      drug delivery and gene transfer.
AB  - Developing safe and effective nanocarriers for multitype of delivery system is
      advantageous for several kinds of successful biomedicinal therapy with the same
      carrier. In the present study, we have designed amino acid biomolecules derived
      hybrid block copolymers which can act as a promising vehicle for both drug
      delivery and gene transfer. Two representative natural chiral amino acid
      containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via
      reversible addition-fragmentation chain transfer (RAFT) process in the presence
      of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn
      CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic
      block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid
      methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar
      aggregation of these amphiphilic block copolymers were studied by fluorescence
      spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy
      (SEM). Potential applications of these hybrid polymers as drug carrier have been
      demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into
      the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups
      in the amphiphilic block copolymers subsequently transformed them into double
      hydrophilic pH-responsive cationic block copolymers having primary amino groups
      in the side-chain terminal. The DNA binding ability of these cationic block
      copolymers were further investigated by using agarose gel retardation assay and
      AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and
      these polymers can serve as "smart" materials for promising bioapplications. 

PMID- 24274732
TI  - Tyrosine kinase inhibitor-induced vasculopathy in clear cell renal cell
      carcinoma: an unrecognized antitumour mechanism.
AB  - AIMS: To evaluate the pathological features of clear cell renal cell carcinoma
      (CCRCC) treated with tyrosine kinase inhibitors (TKIs), and to elucidate the
      mechanism of action of TKIs. METHODS AND RESULTS: Twenty cases of CCRCC treated
      with TKIs (sorafenib or sunitinib) were retrospectively analysed: 16 were
      patients who had undergone radical nephrectomy after neoadjuvant TKI therapy, and
      four were autopsy cases of patients who received TKI treatment. All tumours had
      two distinct regions: one characterized by necrosis and/or degeneration,
      indicating antitumour activity; and the other characterized by no or few
      pathological changes, indicating the absence of antitumour activity. Vasculopathy
      of tumour vessels was observed in or adjacent to the necrotic or degenerative
      areas; a decreased density of endothelial cells was noted in the tumour vessels.
      Few or no changes of vasculopathy were observed in tumour vessels in the other
      CCRCC areas, indicating the absence or low levels of antitumour activity.
      CONCLUSIONS: This is the first pathological report of vasculopathy in TKI-treated
      CCRCC cases. Our data suggest that TKIs initially induce vasculopathy in tumour
      vessels, and consequently cause reduction or diminution of blood supply to the
      CCRCCs, resulting in antitumour activity characterized by necrosis and
      hyalinization.

PMID- 24274733
TI  - Measuring the nursing work environment: translation and psychometric evaluation
      of the Essentials of Magnetism.
AB  - AIM: Translate the Essentials of Magnetism II(c) (EOMII; Dutch Nurses'
      Association, Utrecht, The Netherlands) and assess its psychometric properties in
      a culture different from its origin. BACKGROUND: The EOMII, developed in the USA,
      measures the extent to which organizations/units provide healthy, productive and
      satisfying work environments. As many healthcare organizations are facing
      difficulties in attracting and retaining staff nurses, the EOMII provides the
      opportunity to assess the health and effectiveness of work environments. METHODS:
      A three-phased (respectively N = 13, N = 74 and N = 2542) combined descriptive
      and correlational design was undertaken for translation and evaluation validity
      and psychometric qualities of the EOMII for Dutch hospitals (December 2009
      January 2010). We performed forward-backward translation, face and content
      validation via cross-sectional survey research, and semi-structured interviews on
      relevance, clarity, and recognizability of instruments' items. Psychometric
      testing included principal component analysis using varimax rotation, item-total
      statistics, and reliability in terms of internal consistency (Cronbach's alpha)
      for the total scale and its subscales. RESULTS: Face validity was confirmed.
      Items were recognizable, relevant and clear. Confirmatory factor analysis
      indicated that five of eight subscales formed clear factors. Three original
      subscales contained two factors. Item-total correlations ranged from 0.43 to
      0.83. One item correlated weakly (0.24) with its subscale. Cronbach's alpha for
      the entire scale was 0.92 and ranged from 0.58 to 0.92 for eight subscales.
      CONCLUSIONS: Dutch-translated EOMII (D-EOMII) demonstrated acceptable reliability
      and validity for assessing hospital staff nurses' work environment. IMPLICATIONS
      FOR NURSING AND HEALTH POLICY: The D-EOMII can be useful and effective in
      identifying areas in which change is needed for a hospital to pursue an excellent
      work environment that attracts and retains well-qualified nurses.

PMID- 24274734
TI  - Phonon-assisted exciton transfer into silicon using nanoemitters: the role of
      phonons and temperature effects in Forster resonance energy transfer.
AB  - We study phonon-assisted Forster resonance energy transfer (FRET) into an
      indirect band-gap semiconductor using nanoemitters. The unusual temperature
      dependence of this energy transfer, which is measured using the donor
      nanoemitters of quantum dot (QD) layers integrated on the acceptor
      monocrystalline bulk silicon as a model system, is predicted by a phonon-assisted
      exciton transfer model proposed here. The model includes the phonon-mediated
      optical properties of silicon, while considering the contribution from the
      multimonolayer-equivalent QD film to the nonradiative energy transfer, which is
      derived with a d(-3) distance dependence. The FRET efficiencies are
      experimentally observed to decrease at cryogenic temperatures, which are well
      explained by the model considering the phonon depopulation in the indirect band
      gap acceptor together with the changes in the quantum yield of the donor. These
      understandings will be crucial for designing FRET-enabled sensitization of
      silicon based high-efficiency excitonic systems using nanoemitters. 

PMID- 24274735
TI  - Simple additive-free method to manganese monoxide mesocrystals and their template
      application for the synthesis of carbon and graphitic hollow octahedrons.
AB  - Mesocrystals are of great importance owing to their novel hierarchical
      microstructures and potential applications. In the present work, a simple
      additive-free method has been developed for the controllable synthesis of
      manganese monoxide (MnO) mesocrystals, in which cheap manganese acetate (Mn(Ac)2)
      and ethanol were used as raw materials without involving any other expensive
      additives such as surfactants, polyelectrolyte, or polymers. The particle size of
      the resulting MnO mesocrystals is tunable in the range 400-1500 nm by simply
      altering the concentration of Mn(Ac)2 in ethanol. The percentage yield of the
      octahedral MnO mesocrystals is about 38 wt % with respect to the starting
      Mn(Ac)2. The selective adsorption of oligomers, which was resulted from the
      polymerization of ethanol, acted as an important role for the mesocrystal
      formation. A mechanism involving the oriented aggregation of MnO nanoparticle
      subunits and the subsequent ripening process was proposed. Moreover, for the
      first time, the as-synthesized MnO mesocrystals were employed as a novel template
      to fabricate functional materials with an octahedral morphology including MnO@C
      core/shells, carbon, and graphitic hollow octahedrons. This method shows the
      importance of mesocrystals not only for the field of material research but also
      for the application in functional materials synthesis. 

PMID- 24274736
TI  - Inflammasomes and metabolic disease.
AB  - Innate immune response pathways and metabolic pathways are evolutionarily
      conserved throughout species and are fundamental to survival. As such, the
      regulation of whole-body and cellular metabolism is intimately integrated with
      immune responses. However, the introduction of new variables to this delicate
      evolutionarily conserved physiological interaction can lead to deleterious
      consequences for organisms as a result of inappropriate immune responses. In
      recent decades, the prevalence and incidence of metabolic diseases associated
      with obesity have dramatically increased worldwide. As a recently acquired human
      characteristic, obesity has exposed the critical role of innate immune pathways
      in multiple metabolic pathophysiological processes. Here, we review recent
      evidence that highlights inflammasomes as critical sensors of metabolic
      perturbations in multiple tissues and their role in the progression of highly
      prevalent metabolic diseases. 

PMID- 24274738
TI  - Tobacco smoke-induced lung fibrosis and emphysema.
AB  - Despite public health campaigns discouraging smoking, 1,000 American children
      every day become smokers, ensuring that tobacco-related health complications will
      be with us for decades to come. Smoking is the greatest risk factor for both
      chronic obstructive lung disease and interstitial lung disease. The facts that
      not every smoker develops chronic lung disease and that lung pathology differs
      markedly among smokers indicate that individual susceptibility must be a central
      determinant of lung injury responses to cigarette smoke. Comparative examination
      of pathogenic mechanisms of smoke-induced lung disease can shed light on the
      homeostatic pathways critical to maintaining lung health. In this review, we
      explore common and divergent biological forces tilting the lung homeostatic
      balance away from health and toward emphysema or pulmonary fibrosis. We emphasize
      recent insights that highlight the greatest contrasts or similarities in the
      pathogenesis of these two chronic lung disease phenotypes. 

PMID- 24274737
TI  - Molecular mechanisms for synchronous, asynchronous, and spontaneous
      neurotransmitter release.
AB  - Most neuronal communication relies upon the synchronous release of
      neurotransmitters, which occurs through synaptic vesicle exocytosis triggered by
      action potential invasion of a presynaptic bouton. However, neurotransmitters are
      also released asynchronously with a longer, variable delay following an action
      potential or spontaneously in the absence of action potentials. A compelling body
      of research has identified roles and mechanisms for synchronous release, but
      asynchronous release and spontaneous release are less well understood. In this
      review, we analyze how the mechanisms of the three release modes overlap and what
      molecular pathways underlie asynchronous and spontaneous release. We conclude
      that the modes of release have key fusion processes in common but may differ in
      the source of and necessity for Ca(2+) to trigger release and in the identity of
      the Ca(2+) sensor for release. 

PMID- 24274741
TI  - Encephalopathic Susac's Syndrome associated with livedo racemosa in a young woman
      before the completion of family planning.
AB  - BACKGROUND: Susac's Syndrome (SS) consists of the triad of encephalopathy, branch
      retinal artery occlusions (BRAO) and hearing loss (HL). Histopathologically, SS
      is characterised by a microangiopathy, and some observations suggest that an
      immune-mediated damage of endothelial cells might play a role. These findings
      also implicate a similarity between SS and other autoimmune diseases, most
      notably juvenile dermatomyositis (JDM). However, SS and JDM are commonly thought
      to affect distinct and non-overlapping sets of organs, and it is currently not
      clear how these specificities arise. Moreover, in the absence of clinical trials,
      some authors suggest that therapeutic approaches in SS should rely on the model
      of other autoimmune diseases such as JDM. CASE PRESENTATION: Here, we report a
      case of SS in a 32-year-old pregnant woman. She initially was admitted to the
      hospital with subacute severe encephalopathy and multifocal neurologic signs. As
      cranial magnetic resonance imaging (MRI) revealed multifocal white matter lesions
      including the corpus callosum, erroneously a diagnosis of multiple sclerosis (MS)
      was made, and intravenous methylprednisolone (IVMP) therapy was initiated. A few
      days later, an exanthema appeared on the trunk and extremities, which was
      diagnosed as livedo racemosa (LR). Several weeks later, the patient was
      readmitted to the clinic with an obscuration of her left visual hemifield and a
      bilateral HL. Ophthalmologic examination revealed extensive ischemic damage to
      both retinae. Now the correct diagnosis of SS was established, based on the above
      triad of clinical symptoms in conjunction with typical MRI and fundoscopic
      findings. When SS was diagnosed, the standard therapy with intravenous
      cyclophosphamide (IVCTX) was not instituted because of a significant risk of
      permanent infertility. Instead, sustained control of disease activity could be
      achieved with a therapeutic regime combining prednisolone, intravenous
      immunoglobulins (IVIG), mycophenylate mofetil (MM), and methotrexate (MTX).
      CONCLUSIONS: An association with LR has only been described in very few cases of
      SS before and further underlines the pathogenetic relationship between SS and
      other autoimmune diseases such as JDM. In young women with SS and the desire for
      a child the combination of MM and MTX may represent a reasonable alternative to
      IVCTX.

PMID- 24274739
TI  - Feed your head: neurodevelopmental control of feeding and metabolism.
AB  - During critical periods of development early in life, excessive or scarce
      nutritional environments can disrupt the development of central feeding and
      metabolic neural circuitry, leading to obesity and metabolic disorders in
      adulthood. A better understanding of the genetic networks that control the
      development of feeding and metabolic neural circuits, along with knowledge of how
      and where dietary signals disrupt this process, can serve as the basis for future
      therapies aimed at reversing the public health crisis that is now building as a
      result of the global obesity epidemic. This review of animal and human studies
      highlights recent insights into the molecular mechanisms that regulate the
      development of central feeding circuitries, the mechanisms by which gestational
      and early postnatal nutritional status affects this process, and approaches aimed
      at counteracting the deleterious effects of early over- and underfeeding. 

PMID- 24274740
TI  - Exocytosis and endocytosis: modes, functions, and coupling mechanisms.
AB  - Vesicle exocytosis releases content to mediate many biological events, including
      synaptic transmission essential for brain functions. Following exocytosis,
      endocytosis is initiated to retrieve exocytosed vesicles within seconds to
      minutes. Decades of studies in secretory cells reveal three exocytosis modes
      coupled to three endocytosis modes: (a) full-collapse fusion, in which vesicles
      collapse into the plasma membrane, followed by classical endocytosis involving
      membrane invagination and vesicle reformation; (b) kiss-and-run, in which the
      fusion pore opens and closes; and (c) compound exocytosis, which involves
      exocytosis of giant vesicles formed via vesicle-vesicle fusion, followed by bulk
      endocytosis that retrieves giant vesicles. Here we review these exo- and
      endocytosis modes and their roles in regulating quantal size and synaptic
      strength, generating synaptic plasticity, maintaining exocytosis, and clearing
      release sites for vesicle replenishment. Furthermore, we highlight recent
      progress in understanding how vesicle endocytosis is initiated and is thus
      coupled to exocytosis. The emerging model is that calcium influx via voltage
      dependent calcium channels at the calcium microdomain triggers endocytosis and
      controls endocytosis rate; calmodulin and synaptotagmin are the calcium sensors;
      and the exocytosis machinery, including SNARE proteins (synaptobrevin, SNAP25,
      and syntaxin), is needed to coinitiate endocytosis, likely to control the amount
      of endocytosis. 

PMID- 24274742
TI  - Concurrent parasitic infections in a renal transplant patient.

PMID- 24274744
TI  - Use of social media in urology: data from the American Urological Association
      (AUA).
AB  - OBJECTIVE: To characterise the use of social media among members of the American
      Urological Association (AUA), as the use of social media in medicine has greatly
      expanded in recent years. SUBJECTS AND METHODS: In December 2012 to January 2013,
      the AUA e-mailed a survey with 34 questions on social media use to 2000 randomly
      selected urologists and 2047 resident/fellow members. Additional data was
      collected from Symplur analytics on social media use surrounding the AUA Annual
      Meeting in May 2013. RESULTS: In all, 382 (9.4%) surveys were completed,
      indicating 74% of responders had an online social media account. The most
      commonly used social media platforms were Facebook (93%), followed in descending
      order by LinkedIn (46%), Twitter (36%) and Google+ (26%). Being aged <40 years
      was an important predictor of social media use (83% vs 56%), with greater uptake
      among residents/fellows compared with attendings (86% vs 66%). Only 28% of
      respondents used social media partly or entirely for professional purposes.
      During the 2013 AUA Annual Meeting, there were >5000 tweets from >600 distinct
      contributors. CONCLUSION: As of early 2013, among respondents to an e-mail
      survey, most urologists and urology trainees used some form of social media, and
      its use in urology conferences has greatly expanded.

PMID- 24274745
TI  - Novel reassortant influenza A(H1N2) virus derived from A(H1N1)pdm09 virus
      isolated from swine, Japan, 2012.
AB  - We isolated a novel influenza virus A(H1N2) strain from a pig on January 13,
      2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain
      was a novel type of double-reassortant virus derived from the swine influenza
      virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time. 

PMID- 24274743
TI  - Experimental liver fibrosis research: update on animal models, legal issues and
      translational aspects.
AB  - Liver fibrosis is defined as excessive extracellular matrix deposition and is
      based on complex interactions between matrix-producing hepatic stellate cells and
      an abundance of liver-resident and infiltrating cells. Investigation of these
      processes requires in vitro and in vivo experimental work in animals. However,
      the use of animals in translational research will be increasingly challenged, at
      least in countries of the European Union, because of the adoption of new animal
      welfare rules in 2013. These rules will create an urgent need for optimized
      standard operating procedures regarding animal experimentation and improved
      international communication in the liver fibrosis community. This review gives an
      update on current animal models, techniques and underlying pathomechanisms with
      the aim of fostering a critical discussion of the limitations and potential of up
      to-date animal experimentation. We discuss potential complications in
      experimental liver fibrosis and provide examples of how the findings of studies
      in which these models are used can be translated to human disease and therapy. In
      this review, we want to motivate the international community to design more
      standardized animal models which might help to address the legally requested
      replacement, refinement and reduction of animals in fibrosis research. 

PMID- 24274746
TI  - Enzyme architecture: the activating oxydianion binding domain for orotidine 5'
      monophophate decarboxylase.
AB  - Orotidine 5'-monophosphate decarboxylase catalyzes the decarboxylation of
      truncated substrate (1-beta-D-erythrofuranosyl)orotic acid to form (1-beta-D
      erythrofuranosyl)uracil. This enzyme-catalyzed reaction is activated by
      tetrahedral oxydianions, which bind weakly to unliganded OMPDC and tightly to the
      enzyme-transition state complex, with the following intrinsic oxydianion binding
      energies (kcal/mol): SO3(2-), -8.3; HPO3(2-), -7.7; S2O3(2-), -4.6; SO4(2-), 
      4.5; HOPO3(2-), -3.0; HOAsO3(2-), no activation detected. We propose that the
      oxydianion and orotate binding domains of OMPDC perform complementary functions
      in catalysis of decarboxylation reactions: (1) The orotate binding domain carries
      out decarboxylation of the orotate ring. (2) The activating oxydianion binding
      domain has the cryptic function of utilizing binding interactions with
      tetrahedral inorganic oxydianions to drive an enzyme conformational change that
      results in the stabilization of transition states at the distant orotate domain.

PMID- 24274747
TI  - Economic benefits of safety-engineered sharp devices in Belgium - a budget impact
      model.
AB  - BACKGROUND: Measures to protect healthcare workers where there is risk of injury
      or infection from medical sharps became mandatory in the European Union (EU) from
      May 2013. Our research objective was to estimate the net budget impact of
      introducing safety-engineered devices (SEDs) for prevention of needlestick
      injuries (NSIs) in a Belgian hospital. METHODS: A 5-year incidence-based budget
      impact model was developed from the hospital inpatient perspective, comparing
      costs and outcomes with SEDs and prior-used conventional (non-safety) devices.
      The model accounts for device acquisition costs and costs of NSI management in 4
      areas of application where SEDs are currently used: blood collection, infusion,
      injection and diabetes insulin administration. Model input data were sourced from
      the Institut National d'Assurance Maladie-Invalidite, published studies, clinical
      guidelines and market research. Costs are discounted at 3%. RESULTS: For a 420
      bed hospital, 100% substitution of conventional devices by SEDs is estimated to
      decrease the cumulative 5-year incidence of NSIs from 310 to 75, and those
      associated with exposure to blood-borne viral diseases from 60 to 15. Cost
      savings from managing fewer NSIs more than offset increased device acquisition
      costs, yielding estimated 5-year overall savings of ?51,710. The direction of
      these results is robust to a range of sensitivity and model scenario analyses.
      The model was most sensitive to variation in the acquisition costs of SEDs, rates
      of NSI associated with conventional devices, and the acquisition costs of
      conventional devices. CONCLUSIONS: NSIs are a significant potential risk with the
      use of sharp devices. The incidence of NSIs and the costs associated with their
      management can be reduced through the adoption of safer work practices, including
      investment in SEDs. For a Belgian hospital, the budget impact model reports that
      the incremental acquisition costs of SEDs are offset by the savings from fewer
      NSIs. The availability of more robust data for NSI reduction rates, and
      broadening the scope of the model to include ancillary measures for hospital
      conversion to SED usage, outpatient and paramedic device use, and transmission of
      other blood-borne diseases, would strengthen the model.

PMID- 24274748
TI  - Breathing intolerance index in healthy infants.
AB  - BACKGROUND: The breathing intolerance index (BITI) is used to justify ventilator
      use in adult patients with pulmonary or chest wall disease. BITI in ventilated
      patients is mostly >=0.15. The mean BITI of healthy adults in the upright sitting
      position and the supine position is 0.050 +/- 0.009 and 0.057 +/- 0.016,
      respectively. The aim of this study was to establish a normal BITI in infants.
      METHODS: Thirty healthy infants were examined in the supine position. BITI was
      defined as BITI = (Ti/Ttot) * (TV/VC), where Ti is inspiratory time, Ttot is
      total breath cycle duration, TV is tidal volume, and VC is vital capacity. TV and
      Ti/Ttot were obtained from tidal breathing at rest and VC was obtained
      spirometrically. BITI was calculated using customized software. RESULTS: The mean
      +/- SD BITI of 30 healthy infants in the supine position was 0.120 +/- 0.013. The
      BITI of infants was significantly higher than that of adults. CONCLUSIONS: BITI
      was measured in healthy infants. Further evaluation is needed to determine the
      significance and usefulness of BITI.

PMID- 24274749
TI  - Synthesis, structure, and properties of a series of chiral tweezer-diamine
      complexes consisting of an achiral zinc(II) bisporphyrin host and chiral diamine
      guest: induction and rationalization of supramolecular chirality.
AB  - We report here the synthesis, structure, and spectroscopic properties of a series
      of supramolecular chiral 1:1 tweezer-diamine complexes consisting of an achiral
      Zn(II) bisporphyrin (Zn2DPO) host and five different chiral diamine guests,
      namely, (R)-diaminopropane (DAP), (1S,2S)-diaminocyclohexane (CHDA), (S)
      phenylpropane diamine (PPDA), (S)-phenyl ethylenediamine (PEDA), and (1R,2R)
      diphenylethylene diamine (DPEA). The solid-state structures are preserved in
      solution, as reflected in their (1)H NMR spectra, which also revealed the
      remarkably large upfield shifts of the NH2 guest protons with the order
      Zn2DPO.DAP > Zn2DPO.CHDA > Zn2DPO.PPDA> Zn2DPO.PEDA ? Zn2DPO.DPEA, which happens
      to be the order of binding constants of the respective diamines with Zn2DPO. As
      the bulk of the substituent at the chiral center of the guest ligand increases,
      the Zn-Nax distance of the tweezer-diamine complex also increases, which
      eventually lowers the binding of the guest ligand toward the host. Also, the
      angle between the two porphyrin rings gradually increases with increasing bulk of
      the guest in order to accommodate the guest within the bisporphyrin cavity with
      minimal steric clash. The notably high amplitude bisignate CD signal response by
      Zn2DPO.DAP, Zn2DPO.CHDA, and Zn2DPO.PPDA can be ascribed to the complex's high
      stability and the formation of a unidirectional screw as observed in the X-ray
      structures of the complexes. A relatively lower value of CD amplitude shown by
      Zn2DPO.PEDA is due to the lower stability of the complex. The projection of the
      diamine binding sites of the chiral guest would make the two porphyrin
      macrocycles oriented in either a clockwise or anticlockwise direction in order to
      minimize host-guest steric clash. In sharp contrast, Zn2DPO.DPEA shows a very low
      amplitude bisignate CD signal due to the presence of both left- (dictated by the
      pre-existing chirality of (1R,2R)-DPEA) and right-handed screws (dictated by the
      steric differentiation at the chiral center) of the molecule, as evident from X
      ray crystallography. The present work demonstrates a full and unambiguous
      rationalization of the observed chirality transfer processes from the chiral
      guest to the achiral host. 

PMID- 24274750
TI  - Detecting natural selection in genomic data.
AB  - The past fifty years have seen the development and application of numerous
      statistical methods to identify genomic regions that appear to be shaped by
      natural selection. These methods have been used to investigate the macro- and
      microevolution of a broad range of organisms, including humans. Here, we provide
      a comprehensive outline of these methods, explaining their conceptual motivations
      and statistical interpretations. We highlight areas of recent and future
      development in evolutionary genomics methods and discuss ongoing challenges for
      researchers employing such tests. In particular, we emphasize the importance of
      functional follow-up studies to characterize putative selected alleles and the
      use of selection scans as hypothesis-generating tools for investigating
      evolutionary histories. 

PMID- 24274752
TI  - Bacteria and the aging and longevity of Caenorhabditis elegans.
AB  - The molecular genetic analysis of longevity of Caenorhabditis elegans has yielded
      fundamental insights into evolutionarily conserved pathways and processes
      governing the physiology of aging. Recent studies suggest that interactions
      between C. elegans and its microbial environment may influence the aging and
      longevity of this simple host organism. Experimental evidence supports a role for
      bacteria in affecting longevity through distinct mechanisms--as a nutrient
      source, as a potential pathogen that induces double-edged innate immune and
      stress responses, and as a coevolved sensory stimulus that modulates neuronal
      signaling pathways regulating longevity. Motivating this review is the
      anticipation that the molecular genetic dissection of the integrated host immune,
      stress, and neuroendocrine responses to microbes in C. elegans will uncover basic
      insights into the cellular and organismal physiology that governs aging and
      longevity.

PMID- 24274753
TI  - RNA editing in plants and its evolution.
AB  - RNA editing alters the identity of nucleotides in RNA molecules such that the
      information for a protein in the mRNA differs from the prediction of the genomic
      DNA. In chloroplasts and mitochondria of flowering plants, RNA editing changes C
      nucleotides to U nucleotides; in ferns and mosses, it also changes U to C. The
      approximately 500 editing sites in mitochondria and 40 editing sites in plastids
      of flowering plants are individually addressed by specific proteins, genes for
      which are amplified in plant species with organellar RNA editing. These proteins
      contain repeat elements that bind to cognate RNA sequence motifs just 5' to the
      edited nucleotide. In flowering plants, the site-specific proteins interact
      selectively with individual members of a different, smaller family of proteins.
      These latter proteins may be connectors between the site-specific proteins and
      the as yet unknown deaminating enzymatic activity. 

PMID- 24274751
TI  - Organizing principles of mammalian nonsense-mediated mRNA decay.
AB  - Cells use messenger RNAs (mRNAs) to ensure the accurate dissemination of genetic
      information encoded by DNA. Given that mRNAs largely direct the synthesis of a
      critical effector of cellular phenotype, i.e., proteins, tight regulation of both
      the quality and quantity of mRNA is a prerequisite for effective cellular
      homeostasis. Here, we review nonsense-mediated mRNA decay (NMD), which is the
      best-characterized posttranscriptional quality control mechanism that cells have
      evolved in their cytoplasm to ensure transcriptome fidelity. We use protein
      quality control as a conceptual framework to organize what is known about NMD,
      highlighting overarching similarities between these two polymer quality control
      pathways, where the protein quality control and NMD pathways intersect, and how
      protein quality control can suggest new avenues for research into mRNA quality
      control. 

PMID- 24274754
TI  - RNase III: Genetics and function; structure and mechanism.
AB  - RNase III is a global regulator of gene expression in Escherichia coli that is
      instrumental in the maturation of ribosomal and other structural RNAs. We examine
      here how RNase III itself is regulated in response to growth and other
      environmental changes encountered by the cell and how, by binding or processing
      double-stranded RNA (dsRNA) intermediates, RNase III controls the expression of
      genes. Recent insight into the mechanism of dsRNA binding and processing, gained
      from structural studies of RNase III, is reviewed. Structural studies also reveal
      new cleavage sites in the enzyme that can generate longer 3' overhangs. 

PMID- 24274756
TI  - Evidence for right ventricular lipotoxicity in heritable pulmonary arterial
      hypertension.
AB  - RATIONALE: Shorter survival in heritable pulmonary arterial hypertension (HPAH),
      often due to BMPR2 mutation, has been described in association with impaired
      right ventricle (RV) compensation. HPAH animal models are insulin resistant, and
      cells with BMPR2 mutation have impaired fatty acid oxidation, but whether these
      findings affect the RV in HPAH is unknown. OBJECTIVES: To test the hypothesis
      that BMPR2 mutation impairs RV hypertrophic responses in association with lipid
      deposition. METHODS: RV hypertrophy was assessed in two models of mutant Bmpr2
      expression, smooth muscle-specific (Sm22(R899X)) and universal expression
      (Rosa26(R899X)). Littermate control mice underwent the same stress using
      pulmonary artery banding (Low-PAB). Lipid content was assessed in rodent and
      human HPAH RVs and in Rosa26(R899X) mice after metformin administration. RV
      microarrays were performed using human HPAH and control subjects. RESULTS:
      RV/(left ventricle + septum) did not rise directly in proportion to RV systolic
      pressure in Rosa26(R899X) but did in Sm22(R899X) (P < 0.05). Rosa26(R899X) RVs
      demonstrated intracardiomyocyte triglyceride deposition not present in Low-PAB (P
      < 0.05). RV lipid deposition was identified in human HPAH RVs but not in
      controls. Microarray analysis demonstrated defects in fatty acid oxidation in
      human HPAH RVs. Metformin in Rosa26(R899X) mice resulted in reduced RV lipid
      deposition. CONCLUSIONS: These data demonstrate that Bmpr2 mutation affects RV
      stress responses in a transgenic rodent model. Impaired RV hypertrophy and
      triglyceride and ceramide deposition are present as a function of RV mutant Bmpr2
      in mice; fatty acid oxidation impairment in human HPAH RVs may underlie this
      finding. Further study of how BMPR2 mediates RV lipotoxicity is warranted.

PMID- 24274757
TI  - Tuning rectification in single-molecular diodes.
AB  - We demonstrate a new method of achieving rectification in single molecule devices
      using the high-bias properties of gold-carbon bonds. Our design for molecular
      rectifiers uses a symmetric, conjugated molecular backbone with a single
      methylsulfide group linking one end to a gold electrode and a covalent gold
      carbon bond at the other end. The gold-carbon bond results in a hybrid gold
      molecule "gateway" state pinned close to the Fermi level of one electrode.
      Through nonequilibrium transport calculations, we show that the energy of this
      state shifts drastically with applied bias, resulting in rectification at
      surprisingly low voltages. We use this concept to design and synthesize a family
      of diodes and demonstrate through single-molecule current-voltage measurements
      that the rectification ratio can be predictably and efficiently tuned. This
      result constitutes the first experimental demonstration of a rationally tunable
      system of single-molecule rectifiers. More generally, the results demonstrate
      that the high-bias properties of "gateway" states can be used to provide
      additional functionality to molecular electronic systems. 

PMID- 24274758
TI  - Chemical composition of desert willow (Salix psammophila) grown in the Kubuqi
      Desert, Inner Mongolia, China: bark extracts associated with environmental
      adaptability.
AB  - Bark of desert willow (Salix psammophila, Spsa) grown in Inner Mongolia was
      successively extracted with n-hexane, diethyl ether, acetone, methanol, and hot
      water to examine chemical components associated with its environmental
      adaptability to desert conditions. The yield of n-hexane extract (5.0% based on
      dry bark), mainly composed of wax, was higher than those of acetone and methanol
      extracts (3.7% and 4.2%, respectively), whereas the yields of n-hexane extract
      (1.4%) from willow bark grown in humid areas were much lower than those of
      acetone (17.4% and 19.9%) and methanol (12.5% and 14.0%) extracts. Unlike other
      willow bark samples, Spsa bark contained a certain amount of sugar alcohols. In
      particular, we identified arabinitol (0.21%), which has not previously been
      reported as a major component of extracts of willow bark. The high content of wax
      and sugar alcohol would be associated with the ability of Spsa to survive in
      desert conditions. Accumulation of wax on the outer bark surface would reduce
      water loss, while sugar alcohols might improve freezing tolerance. 

PMID- 24274755
TI  - Biology and genetics of prions causing neurodegeneration.
AB  - Prions are proteins that acquire alternative conformations that become self
      propagating. Transformation of proteins into prions is generally accompanied by
      an increase in beta-sheet structure and a propensity to aggregate into oligomers.
      Some prions are beneficial and perform cellular functions, whereas others cause
      neurodegeneration. In mammals, more than a dozen proteins that become prions have
      been identified, and a similar number has been found in fungi. In both mammals
      and fungi, variations in the prion conformation encipher the biological
      properties of distinct prion strains. Increasing evidence argues that prions
      cause many neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's,
      Creutzfeldt-Jakob, and Lou Gehrig's diseases, as well as the tauopathies. The
      majority of NDs are sporadic, and 10% to 20% are inherited. The late onset of
      heritable NDs, like their sporadic counterparts, may reflect the stochastic
      nature of prion formation; the pathogenesis of such illnesses seems to require
      prion accumulation to exceed some critical threshold before neurological
      dysfunction manifests. 

PMID- 24274759
TI  - On the direct electron transfer, sensing, and enzyme activity in the glucose
      oxidase/carbon nanotubes system.
AB  - The signal transduction and enzyme activity were investigated in biosensors based
      on the glucose oxidase (GOx) and carbon nanotubes (CNT) embedded in a bioadhesive
      film of chitosan (CHIT). The voltammetric studies showed that, regardless of CHIT
      matrix, the GOx adsorbed on CNT yielding a pair of surface-confined current peaks
      at -0.48 V. The anodic peak did not increase in the presence of glucose in an O2
      free solution indicating the lack of direct electron transfer (DET) between the
      enzymatically active GOx and CNT. The voltammetric peaks were due to the redox of
      enzyme cofactor flavin adenine dinucleotide (FAD), which was not the part of
      active enzyme. The presented data suggest that DET may not be happening for any
      type of GOx/CNT-based sensor. The biosensor was sensitive to glucose in air
      equilibrated solutions indicating the O2-mediated enzymatic oxidation of glucose.
      The signal transduction relied on the net drop in a biosensor current that was
      caused by a decrease in a 4-e(-) O2 reduction current and an increase in a 2-e(-)
      H2O2 reduction current. The enzyme assays showed that CNT nearly doubled the
      retention of GOx in a biosensor while decreasing the average enzymatic activity
      of retained enzyme by a factor of 4-5. Such inhibition should be considered when
      using a protein-assisted solubilization of CNT in water for biomedical
      applications. The proposed analytical protocols can be also applied to study the
      effects of nanoparticles on proteins in assessing the health risks associated
      with the use of nanomaterials. 

PMID- 24274760
TI  - Combined effects of PEG hydrogel elasticity and cell-adhesive coating on
      fibroblast adhesion and persistent migration.
AB  - The development and use of synthetic, cross-linked, macromolecular substrates
      with tunable elasticity has been instrumental in revealing the mechanisms by
      which cells sense and respond to their mechanical microenvironment. We here
      describe a hydrogel based on radical-free, cross-linked poly(ethylene glycol) to
      study the effects of both substrate elasticity and type of adhesive coating on
      fibroblast adhesion and migration. Hydrogel elasticity was controlled through the
      structure and concentration of branched precursors, which efficiently react via
      Michael-type addition to produce the polymer network. We found that cell
      spreading and focal adhesion characteristics are dependent on elasticity for all
      types of coatings (RGD peptide, fibronectin, vitronectin), albeit with
      significant differences in magnitude. Importantly, fibroblasts migrated slower
      but more persistently on stiffer hydrogels, with the effects being more
      pronounced on fibronectin-coated substrates. Therefore, our results validate the
      hydrogels presented in this study as suitable for future mechanosensing studies
      and indicate that cell adhesion, polarity, and associated migration persistence
      are tuned by substrate elasticity and biochemical properties. 

PMID- 24274761
TI  - Heterojunction PbS nanocrystal solar cells with oxide charge-transport layers.
AB  - Oxides are commonly employed as electron-transport layers in optoelectronic
      devices based on semiconductor nanocrystals, but are relatively rare as hole
      transport layers. We report studies of NiO hole-transport layers in PbS
      nanocrystal photovoltaic structures. Transient fluorescence experiments are used
      to verify the relevant energy levels for hole transfer. On the basis of these
      results, planar heterojunction devices with ZnO as the photoanode and NiO as the
      photocathode were fabricated and characterized. Solution-processed devices were
      used to systematically study the dependence on nanocrystal size and achieve
      conversion efficiency as high as 2.5%. Optical modeling indicates that optimum
      performance should be obtained with thinner oxide layers than can be produced
      reliably by solution casting. Room-temperature sputtering allows deposition of
      oxide layers as thin as 10 nm, which enables optimization of device performance
      with respect to the thickness of the charge-transport layers. The best devices
      achieve an open-circuit voltage of 0.72 V and efficiency of 5.3% while
      eliminating most organic material from the structure and being compatible with
      tandem structures. 

PMID- 24274762
TI  - The association of attention deficit hyperactivity disorder with socioeconomic
      disadvantage: alternative explanations and evidence.
AB  - BACKGROUND: Studies throughout Northern Europe, the United States and Australia
      have found an association between childhood attention deficit hyperactivity
      disorder (ADHD) and family socioeconomic disadvantage. We report further evidence
      for the association and review potential causal pathways that might explain the
      link. METHOD: Secondary analysis of a UK birth cohort (the Millennium Cohort
      Study, N = 19,519) was used to model the association of ADHD with socioeconomic
      disadvantage and assess evidence for several potential explanatory pathways. The
      case definition of ADHD was a parent-report of whether ADHD had been identified
      by a medical doctor or health professional when children were 7 years old.
      RESULTS: ADHD was associated with a range of indicators of social and economic
      disadvantage including poverty, housing tenure, maternal education, income, lone
      parenthood and younger motherhood. There was no evidence to suggest childhood
      ADHD was a causal factor of socioeconomic disadvantage: income did not decrease
      for parents of children with ADHD compared to controls over the 7-year study
      period. No clinical bias towards labelling ADHD in low SES groups was detected.
      There was evidence to suggest that parent attachment/family conflict mediated the
      relationship between ADHD and SES. CONCLUSION: Although genetic and neurological
      determinants may be the primary predictors of difficulties with activity level
      and attention, aetiology appears to be influenced by socioeconomic situation.

PMID- 24274763
TI  - Identification of novel downstream molecules of tissue factor activation by
      comparative proteomic analysis.
AB  - Tissue factor (TF) is both an initiator of blood coagulation and a signaling
      receptor. Using a proteomic approach, we investigated the role of TF in cell
      signaling when stimulated by its ligand, activated factor VII (FVIIa). From a 2-D
      difference gel electrophoresis (DIGE) study we found forty one spots that were
      differentially regulated over time in FVIIa stimulated cells or in comparison to
      nonstimulated cells. Mass spectrometry identifies 23 out of these as 13 different
      proteins. One of them, elongation factor 2 (EF-2), was investigated in greater
      detail by Western blot, a protein synthesis assay and cell cycle analysis. When
      tissue factor was stimulated by FVIIa, the phosphorylation of EF-2 increased
      which inactivates this protein. Analyzing the effect using site inactivated FVIIa
      (FVIIai), as well as the protease activated receptor 2 (PAR-2) agonist SLIGKV,
      indicated that the inactivation was not PAR-2 dependent. A panel of tissue factor
      mutants was analyzed further to try to pinpoint what part of the cytoplasmic
      domain that is needed for this effect. Performing a protein synthesis assay in
      two different cell lines we could confirm that protein synthesis decreased upon
      stimulation by FVIIa. Cell cycle analysis showed that FVIIa also promotes a
      higher degree of cell proliferation. 

PMID- 24274764
TI  - Emotional stress-reactivity and positive affect among college students: the role
      of depression history.
AB  - Multiple theories posit that people with a history of depression are at higher
      risk for a depressive episode than people who have never experienced depression,
      which may be partly due to differences in stress-reactivity. In addition, both
      the dynamic model of affect and the broaden-and-build theory suggest that stress
      and positive affect interact to predict negative affect, but this moderation has
      never been tested in the context of depression history. The current study used
      multilevel modeling to examine these issues among 1,549 college students with or
      without a history of depression. Students completed a 30-day online diary study
      in which they reported daily their perceived stress, positive affect, and
      negative affect (including depression, anxiety, and hostility). On days
      characterized by higher than usual stress, students with a history of depression
      reported greater decreases in positive affect and greater increases in depressed
      affect than students with no history. Furthermore, the relations between daily
      stress and both depressed and anxious affect were moderated by daily positive
      affect among students with remitted depression. These results indicate that
      students with a history of depression show greater stress-reactivity even when in
      remission, which may place them at greater risk for recurrence. These individuals
      may also benefit more from positive affect on higher stress days despite being
      less likely to experience positive affect on such days. The current findings have
      various implications both clinically and for research on stress, mood, and
      depression. (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24274765
TI  - Distinct sources of self-discrepancies: effects of being who you want to be and
      wanting to be who you are on well-being.
AB  - Self-discrepancy theory contends that well-being depends, in part, on the amount
      of overlap between one's actual and ideal selves. There is a variety of
      supportive evidence, but Rabbi Hyman Schachtel's (1954, The real enjoyment of
      living, New York, NY, Dutton) contention that "happiness is not having what you
      want, but wanting what you have" (p. 37) highlights that a distinction between
      two potential sources of overlap between one's actual and ideal selves has been
      overlooked. Whereas most measures of ideal self-discrepancies index the extent to
      which people are who they want to be (i.e., ideal self-actualization [ISA]),
      others index the extent to which people want to be who they are (i.e., actual
      self-regard [ASR]). In several studies, we measured ideal self-actualization by
      asking people to identify traits they would ideally like to possess and rate the
      extent to which they had those traits. We also measured actual self-regard by
      asking participants to identify traits they possessed and indicate the extent to
      which they wanted those traits. In all 4 studies, ideal self-actualization and
      actual self-regard were distinct from one another (rs = .24 to .32) and both were
      distinct from self-compassion (Study 1) and global self-esteem (Study 4).
      Moreover, ASR consistently accounted for unique variance in aspects of well-being
      (e.g., subjective well-being, positive affect, psychological growth) and ISA
      often did so. Finally, a longitudinal study provided evidence that actual self
      regard is a precursor, but not a consequence, of subjective well-being (Study 4).

PMID- 24274766
TI  - Restoration of WNT4 inhibits cell growth in leukemia-derived cell lines.
AB  - BACKGROUND: WNT signaling pathways are significantly altered during cancer
      development. Vertebrates possess two classes of WNT signaling pathways: the
      "canonical" WNT/beta-catenin signaling pathway, and the "non-canonical" pathways
      including WNT/Ca2+ and WNT/Planar cell polarity [PCP] signaling. WNT4 influences
      hematopoietic progenitor cell expansion and survival; however, WNT4 function in
      cancer development and the resulting implications for oncogenesis are poorly
      understood.The aim of this study was twofold: first, to determine the expression
      of WNT4 in mature peripheral blood cells and diverse leukemia-derived cells
      including cell lines from hematopoietic neoplasms and cells from patients with
      leukemia; second, to identify the effect of this ligand on the proliferation and
      apoptosis of the blast-derived cell lines BJAB, Jurkat, CEM, K562, and HL60.
      METHODS: We determined WNT4 expression by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) in peripheral blood mononuclear cells (PBMCs)
      and T- and B-lymphocytes from healthy individuals, as well as from five leukemia
      derived cell lines and blasts derived from patients with leukemia. To analyze the
      effect of WNT4 on cell proliferation, PBMCs and cell lines were exposed to a
      commercially available WNT4 recombinant human protein. Furthermore, WNT4
      expression was restored in BJAB cells using an inducible lentiviral expression
      system. Cell viability and proliferation were measured by the addition of WST-1
      to cell cultures and counting cells; in addition, the progression of the cell
      cycle and the amount of apoptosis were analyzed in the absence or presence of
      WNT4. Finally, the expression of WNT-pathway target genes was measured by qRT
      PCR. RESULTS: WNT4 expression was severely reduced in leukemia-derived cell lines
      and blasts derived from patients with leukemia. The exposure of cell lines to
      WNT4 recombinant protein significantly inhibited cell proliferation; inducing
      WNT4 expression in BJAB cells corroborated this observation. Interestingly,
      restoration of WNT4 expression in BJAB cells increased the accumulation of cells
      in G1 phase, and did not induce activation of canonical WNT/beta-catenin target
      genes. CONCLUSIONS: Our findings suggest that the WNT4 ligand plays a role in
      regulating the cell growth of leukemia-derived cells by arresting cells in the G1
      cell cycle phase in an FZD6-independent manner, possibly through antagonizing the
      canonical WNT/beta-catenin signaling pathway.

PMID- 24274767
TI  - Low temperature thermal dependent Filgrastim adsorption behavior detected with
      ToF-SIMS.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) detected changes in
      Filgrastim (granulocyte colony stimulating growth factor, G-CSF) adsorption
      behavior at a solid interface when exposed to temperatures as low as 35  degrees
      C, i.e., before thermal denaturation, was detected by circular dichroism (CD) or
      dynamic light scattering (DLS). Biopharmaceuticals rely on maintaining sufficient
      conformation to impart correct biological function in vivo. Stability of such
      molecules is critical during synthesis, storage, transport, and administration.
      CD analysis indicated loss of structure at temperatures greater than ~60  degrees
      C, while DLS detected aggregation at ~42  degrees C. Furthermore, we demonstrate
      the nature of G-CSF interaction with a surface was altered rapidly and at
      relatively low temperatures. Specifically, after 10 min thermal treatment,
      changes in adsorption behavior occurred at 35  degrees C indicated by principal
      component analysis of spectra as primarily due to increasing yields of methionine
      fragments. This was likely to be due to either altering the preferential protein
      orientation upon adsorption or greater denaturation exposing the hydrophobic
      core. This investigation demonstrates the sensitivity of ToF-SIMS in studying
      biopharmaceutical adsorption and conformational change and can assist with
      studies into promoting their stability.

PMID- 24274768
TI  - Views of mammography screening among U.S. Black and Hispanic immigrant women and
      their providers.
AB  - Views of ethnic immigrant women's experiences about mammography screening are
      important to determine barriers to cancer screening. We explored perceptions and
      barriers about mammography screening and breast health services among Haitian,
      Hispanic, Portuguese, and Somali women (n = 51) using semistructured interviews.
      Providers (n = 19) offered insight into health system barriers. Content analysis
      was conducted using qualitative data from the 2011 Komen Massachusetts needs
      assessment. Grounded theory was employed to explore themes and patterns in
      narratives. Six themes represented knowledge, health care, culture, spirituality,
      survivorship, and health systems improvement. Results may inform breast health
      policies that impact ethnic immigrant women in Massachusetts. 

PMID- 24274769
TI  - Comparison of the electrochemical performance of NiMoO4 nanorods and hierarchical
      nanospheres for supercapacitor applications.
AB  - Much attention has been paid to exploring electrode materials with enhanced
      supercapacitor performance as well as relatively low cost and environmental
      friendliness. In this work, NiMoO4 nanospheres and nanorods were synthesized by
      facile hydrothermal methods. The hierarchical NiMoO4 nanospheres were about 2.5
      MUm in diameter and assembled from thin mesoporous nanosheets with a thickness of
      about 10-20 nm. The NiMoO4 nanorods were about 80 nm in diameter and about 300 nm
      to 1 MUm in length. Their electrochemical properties were investigated for use as
      electrode materials for supercapacitors (SCs). The NiMoO4 nanospheres exhibited a
      higher specific capacitance and better cycling stability and rate capability,
      which were attributed to their large surface area and high electrical
      conductivity. The specific capacitances were 974.4, 920.8, 875.5, 859.1, and
      821.4 F/g at current densities of 1, 2, 4, 6, and 10 A/g, respectively.
      Remarkably, the energy density was able to reach 20.1 Wh/kg at a power density of
      2100 W/kg. After 2000 cycles, the NiMoO4 nanospheres still displayed a high
      specific capacitance of about 631.8 F/g at a current density of 5 A/g. These
      results implied that the hierarchical NiMoO4 nanospheres could be a promising
      candidate for use as high-performance SCs.

PMID- 24274770
TI  - Structure prediction of Au(44)(SR)(28): a chiral superatom cluster.
AB  - The structure of a thiolate-protected Au44 cluster, [Au44(SR)28], is
      theoretically predicted via density functional theory calculations. Au44(SR)28 is
      predicted to contain a "two-shell" face-centered-cubic type of Au kernel and
      possess chirality. The predicted cluster structure is validated by comparison of
      optical absorption properties between theory and previous experiments, as well as
      energy evaluations. Based on the predicted cluster structure, the magic stability
      of Au44(SR)28 is understood from the superatom electronic configuration and
      formation of a unique double-helix superatom network inside. 

PMID- 24274771
TI  - Effects of dark chocolate and cocoa consumption on endothelial function and
      arterial stiffness in overweight adults.
AB  - The consumption of cocoa and dark chocolate is associated with a lower risk of
      CVD, and improvements in endothelial function may mediate this relationship. Less
      is known about the effects of cocoa/chocolate on the augmentation index (AI), a
      measure of vascular stiffness and vascular tone in the peripheral arterioles. We
      enrolled thirty middle-aged, overweight adults in a randomised, placebo
      controlled, 4-week, cross-over study. During the active treatment (cocoa) period,
      the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa
      beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched
      controls included a low-flavanol chocolate bar and a cocoa-free beverage with no
      added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat,
      carbohydrates and protein. The cocoa treatment significantly increased the basal
      diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood
      flow volume by 22%. Substantial decreases in the AI, a measure of arterial
      stiffness, were observed in only women. Flow-mediated dilation and the reactive
      hyperaemia index remained unchanged. The consumption of cocoa had no effect on
      fasting blood measures, while the control treatment increased fasting insulin
      concentration and insulin resistance (P= 0.01). Fasting blood pressure (BP)
      remained unchanged, although the acute consumption of cocoa increased resting BP
      by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was
      associated with enhanced vasodilation in both conduit and resistance arteries and
      was accompanied by significant reductions in arterial stiffness in women.

PMID- 24274772
TI  - Association of activated partial thromboplastin time and fibrinogen level in
      patients with type II diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus have a high risk of atherothrombotic
      events. Diabetes contributes for initiation and progression of microvascular and
      macrovascular complications. Shortened activated partial thromboplastin time
      (aPTT) values may reflect hypercoaguable state, which is associated with
      increased thrombotic risk and adverse cardiovascular events. Increased level of
      fibrinogen is common in type II diabetes. The present study was conducted to
      study the aPTT and fibrinogen levels in diabetics in a tertiary care Teaching
      Hospital of Nepal. METHODS: Observational study was performed at out-patients
      visiting Pathology Department at Tribhuvan University Teaching Hospital from
      August 5 to September 7, 2012. Research protocol was approved by Institutional
      Review Board at Tribhuvan University Institute of Medicine. Altogether 90 people
      who came to the hospital during study period and who met inclusion criteria were
      selected, out of which 72 were diabetics and 18 were normal controls. Diabetic
      cases were identified via verbal interview with patients themselves and review of
      laboratory findings and diagnosis performed by their physicians. Diabetics with a
      diabetic history of more than one year and stabilized with antidiabetic medicines
      such as insulin, metformin, glibenclamide, and gliclazide and diabetics with
      controlled diabetes as revealed by HbA1c in the range 6.2-7% were taken for the
      study purpose. Data were analyzed with chi square test and Fischer's exact test
      (when each cell frequency was less than 5) using Statistical Package for Social
      Sciences 17. RESULTS: Maximum (53; 73.6%) diabetics and all non-diabetics had
      aPTT in the range 26-40 seconds. Maximum (51; 70.8%) patients had fibrinogen
      beyond 351 whereas all non-diabetics had fibrinogen in the range 151-350. Mean
      aPTT values of the diabetic patients and non-diabetic persons were 29.88 +/- 4.89
      seconds and 32.44 +/- 2.25 seconds respectively. Mean fibrinogen values of the
      diabetic patients and non-diabetic persons were 388.57 +/- 60.90 mg/dL and 320.89
      +/- 10.20 mg/dL respectively. Test data identified in results were statistically
      significant for aPTT (p value 0.000) and fibrinogen (p value 0.000) between the
      diabetics and non-diabetics. CONCLUSIONS: Diabetics have an increased level of
      fibrinogen and relatively shortened aPTT as compared to the non-diabetic
      patients.

PMID- 24274774
TI  - Editorial.

PMID- 24274773
TI  - Healthcare reform: implications for knowledge translation in primary care.
AB  - BACKGROUND: The primary care sector represents the linchpin of many health
      systems. However, the translation of evidence-based practices into patient care
      can be difficult, particularly during healthcare reform. This can have
      significant implications for patients, their communities, and the public purse.
      This is aptly demonstrated in the area of sexual health. The aim of this paper is
      to determine what works to facilitate evidence-based sexual healthcare within the
      primary care sector. METHODS: 431 clinicians (214 general practitioners and 217
      practice nurses) in New South Wales, Australia, were surveyed about their
      awareness, their use, the perceived impact, and the factors that hindered the use
      of six resources to promote sexual healthcare. Descriptive statistics were
      calculated from the responses to the closed survey items, while responses to open
      ended item were thematically analyzed. RESULTS: All six resources were reported
      to improve the delivery of evidence-based sexual healthcare. Two resources - both
      double-sided A4-placards - had the greatest reach and use. Barriers that hindered
      resource-use included limited time, limited perceived need, and limited access
      to, or familiarity with the resources. Furthermore, the reorganization of the
      primary care sector and the removal of particular medical benefits scheme items
      may have hampered clinician capacity to translate evidence-based practices into
      patient care. CONCLUSIONS: Findings reveal: (1) the translation of evidence-based
      practices into patient care is viable despite reform; (2) the potential value of
      a multi-modal approach; (3) the dissemination of relatively inexpensive resources
      might influence clinical practices; and (4) reforms to governance and/or funding
      arrangements may widen the void between evidence-based practices and patient
      care.

PMID- 24274775
TI  - Motivational beliefs, cognitive engagement, and achievement in language and
      mathematics in elementary school children.
AB  - The contextual differences in the patterns of relations among various
      motivational, cognitive, and metacognitive components of self-regulated learning
      and performance in two key curriculum subject areas, language and mathematics,
      were examined in a sample of 263 Greek primary school children of fifth- and
      sixth-grade classrooms. Age and gender differences were also investigated.
      Students were asked to complete the Motivated Strategies for Learning
      Questionnaire (Pintrich & De Groot, 1990 ), which comprised five factors: (a)
      Self-efficacy, (b) Intrinsic Value, (c) Test Anxiety, (d) Cognitive Strategy Use,
      and (e) Self-regulation Strategies. They responded to the statements of the
      questionnaire on a 7-point Likert scale in terms of their behaviour in
      mathematics and language classes, respectively. Moreover, their teachers were
      asked to evaluate each of their students' academic achievement in Greek language
      and mathematics on a 1- to 20-point comparative scale in relation to the rest of
      the class. The results of the study indicated very few differences in the pattern
      of relations among self-regulated components within and across the two subject
      areas and at the same time revealed a context-specific character of self
      regulated components at a mean level differences. Further, the current study (a)
      confirmed the mediatory role of strategies in the motivation-performance
      relation, (b) stressed the differential role of cognitive and regulatory
      strategies in predicting performance in subject areas that differ in their
      structural characteristics of the content, and (c) pointed out the key
      motivational role of self-efficacy. In fact, self-efficacy proved the most
      significant predictor not only of performance but of cognitive and regulatory
      strategy use as well. Gender differences in motivation and strategy use were not
      reported, while motivation was found to vary mainly with age. The usefulness of
      these findings for promoting greater clarity among motivational and metacognitive
      frameworks and ideas for future research are discussed. Cette etude porte sur les
      differences contextuelles dans les patrons relationnels entre les diverses
      composantes motivationnelle, cognitive et metacognitive de l'apprentissage et de
      la performance auto-regules dans deux domaines d'etude cle du programme, soit la
      langue et les mathematiques. Ces differences contextuelles ont ete examinees dans
      un echantillon de 263 d'enfants d'une ecole primaire grecque (of) en cinquieme et
      sixieme annee. Les differences sexuelles et les differences d'age ont ete aussi
      etudiees. Les eleves ont ete pries de completer le "Motivated Strategies for
      Learning Questionnaire" (Pintrich & De Groot, 1990 ) qui comprend cinq facteurs:
      (a) l'auto-efficacite, (b) la valeur intrinseque, (c) un test d'anxiete, (d)
      l'utilisation d'une strategie cognitive et (e) les strategies d'auto-regulation.
      Ils ont repondu aux enonces du questionnaire sur une echelle de type Likert a 7
      points en termes de leur comportement en classe de langue et en classe de
      mathematiques separement. De plus, les enseignants ont ete pries d'evaluer chaque
      resultat de leurs eleves dans la langue grecque et en mathematique sur une
      echelle allant de 1 a 20 points en comparaison au reste de la classe. Les
      resultats de l'etude ont indique tres peu de differences dans les patrons
      relationnels entre les composantes auto-regulees a l'interieur et entre les
      domaines d'etude. En meme temps, les resultats ont revele un caractere contextuel
      specifique des composantes auto-regulees. De plus, la presente etude (a) a
      confirme le role mediateur des strategies dans la relation motivation
      performance, (b) a souligne le role differe des strategies cognitive et
      regulatoire dans la prediction de la performance dans les domaines d'etude qui
      different dans leurs caracteristiques structurelles du contenu et (c) a souligne
      le role motivationnel cle de l'auto-efficacite. En effet, l'auto-efficacite s'est
      averee etre le predicteur le plus significatif non seulement de la performance
      mais aussi de l'utilisation d'une strategie cognitive et regulatoire. Des
      differences sexuelles dans la motivation et dans l'utilisation d'une strategie
      n'ont pas ete rapportees alors qu'il s'est avere que la motivation variait
      principalement en fonction de l'age. L'utilite de ces resultats pour la promotion
      d'une grande clarte entre les cadres motivationnel et metacognitif et les idees
      pour les etudes futures sont discutees. Se examino, en una muestra de 263 ninos
      griegos de quinto y sexto anos de la escuela primaria, las diferencias
      contextuales en las pautas con las que se dan las relaciones entre varios
      componentes motivacionales, cognitivos y meta cognitivos del aprendizaje
      autorregulado y el desempeno en dos areas clave del curriculo, lenguaje y
      matematicas. Tambien se investigo las diferencias de edad y genero. Se pidio a
      los alumnos que respondieran el Cuestionario de Estrategias Motivadas para el
      Aprendizaje (Pintrich & De Groot, 1990 ), compuesto por cinco factores: (a) Auto
      eficacia, (b) Valor Intrinseco, (c) Ansiedad ante los Examenes, (d) Empleo de
      Estrategias Cognitivas, y (e) Estrategias Autorreguladas. Respondieron a los
      enunciados del cuestionario sobre una escala Likert de 7 puntos en terminos de su
      conducta en las clases de matematicas y lenguaje por separado. Es mas, se pidio a
      sus profesores que evaluaran el desempeno de cada uno de sus estudiantes en
      Lenguaje Griego y Matematicas de acuerdo con una escala comparativa de 1 a 20
      puntos, en relacion con el resto del grupo escolar. Los resultados del estudio
      indicaron pocas diferencias en la pauta que describen las relaciones entre los
      componentes de autorregulacion al interior de y entre ambas areas de estudio y,
      al mismo tiempo, revelaron un caracter especifico del contexto de los componentes
      de la autorregulacion con diferencias en el nivel medio. Mas aun, el presente
      estudio (a) confirmo el papel de mediador que desempenan las estrategias sobre la
      relacion motivacion-desempeno, (b) acentuo el papel diferencial de las
      estrategias cognitiva y reguladora al predecir el desempeno en areas de estudio
      que difieren en las caracteristicas estructurales de su contenido, y (c) senalo
      el papel motivacional clave que desempena la auto eficacia. De hecho, la auto
      eficacia predijo de manera mas significativa no solo el desempeno, sino tambien
      el uso de la estrategia cognitiva y reguladora. No hubo diferencias de genero
      respecto a la motivacion y al uso de la estrategia, aunque se encontro que la
      motivacion varia principalmente con la edad. Se discute la utilidad de estos
      hallazgos para aclarar los referentes motivacionales y meta cognitivos y promover
      ideas para investigaciones futuras. 

PMID- 24274776
TI  - Contemporary attitudes and their ideological representation in Flanders
      (Belgium), Poland, and the Ukraine.
AB  - The present research tests the validity of a two-dimensional cultural and
      economic right-wing model of ideology, as well as the relationships between these
      dimensions and attitudes toward recent political issues. Opinions about
      environmentalism, war on terror, and European Union enlargement were selected as
      representative contemporary attitudes. The present research questions were
      investigated in a Flemish (N = 176), Polish (N = 93), and Ukrainian (N = 93)
      sample. The results revealed that two dimensions underlie the ideological
      spectrum in all samples, one referring to cultural conservatism and right-wing
      authoritarianism (RWA), and one referring to economic conservatism and social
      dominance orientation (SDO). Although the validity of differentiating between
      these ideological dimensions has been amply illustrated in studies on Western
      samples, the replication of these dimensions in former communist countries add to
      their validity and generality, because these countries have a specific political
      culture and history. However, important cross-cultural differences with respect
      to the representation of the contemporary attitudes in this two-dimensional
      ideological space were obtained as well. Whereas the war on terror attitude was
      meaningfully related to the cultural right-wing dimension in all samples, the
      relationships for the environmentalism and EU enlargement attitudes were sample
      dependent. These cross-cultural differences were explained in terms of saliency
      of the issue (nonsignificant versus significant relationships in the case of
      environmentalism) and pragmatic concerns in terms of profits and costs (in the
      case of EU enlargement). In the discussion it is also argued that the closer
      correspondence between the ideological representation of these attitudes in
      Polish and Western society may be caused by the fact that communism was less
      successful in penetrating political mentality in Poland than in the Ukraine. La
      presente recherche teste la validite d'un modele ideologique d'extreme droite a
      deux dimensions culturelle et economique ainsi que les relations entre ces
      dimensions et les attitudes envers les enjeux politiques recents. Les opinions
      sur l'environnementalisme, sur la guerre contre le terrorisme et sur
      l'elargissement de l'Union Europeenne (UE) ont ete selectionnes comme etant des
      attitudes contemporaines representatives. Les presentes questions de recherche
      ont ete examinees dans un echantillon flamand (N = 176), polonais (N = 93) et
      ukrainien (N = 93). Les resultats ont revele que deux dimensions sont sous
      jacentes au spectre ideologique dans tous les echantillons: une de ces dimensions
      refere au conservatisme culturel et a l'autoritarisme d'extreme droite (RWA en
      anglais) et l'autre refere au conservatisme economique et a la theorie de la
      dominance sociale (SDO en anglais). Meme si la validite de la differentiation
      entre ces dimensions ideologiques a ete amplement illustree dans les etudes sur
      les echantillons occidentaux, la replication de ces dimensions dans les anciens
      pays communistes ajoute a leur validite et a leur generalisabilite parce que ces
      pays ont une culture et une histoire politique specifique. Cependant,
      d'importantes differences trans-culturelles en ce qui concerne la representation
      des attitudes contemporaines dans cet espace ideologique a deux dimensions ont
      egalement ete obtenues. Tandis que la guerre contre le terrorisme a ete liee
      significativement a la dimension culturelle d'extreme droite dans tous les
      echantillons, les relations pour l'environnementalisme et les attitudes envers
      l'elargissement de l'UE variaient selon les echantillons. Ces differences trans
      culturelles ont ete expliquees en termes de degre de saillance du sujet
      (relations non significatives versus significatives dans le cas de
      l'environnementalisme) et des soucis pragmatiques quant aux profits et aux couts
      (dans le cas de l'elargissement de l'UE). Dans la discussion, il est aussi
      argumente que la correspondance plus etroite entre la representation ideologique
      de ces attitudes dans les societes polonaise et occidentale peut etre due au fait
      que le communisme a moins reussi a penetrer la mentalite politique en Pologne
      qu'en Ukraine. La presente investigacion somete a prueba la validez de un modelo
      de dos dimensiones, cultural y economico de ideologia de derecha, asi como las
      relaciones entre estas dimensiones y actitudes hacia temas politicos recientes.
      Las opiniones sobre el ambiente, la guerra al terror, y la ampliacion de la Union
      Europea se seleccionaron como actitudes representativas contemporaneas. Se
      investigaron las preguntas de investigacion en muestras flamencas (N = 176),
      polacas (N = 93) y ucranianas (N = 93). Los resultados revelan que subyacen dos
      dimensiones al espectro ideologico en todas las muestras, una se refiere al
      conservadurismo cultural y al autoritarismo de derecha (AD), y otra que se
      refiere al conservadurismo economico y a la orientacion de dominancia social
      (ODS). A pesar de que los estudios en muestras occidentales han ilustrado
      ampliamente la validez de las diferencias entre estas dimensiones ideologicas, la
      replica de estos estudios en paises anteriormente comunistas contribuye a su
      validez y generalidad, porque estos paises poseen una cultura e historia politica
      especifica. Sin embargo, tambien se obtuvieron diferencias interculturales
      importantes respecto a la representacion de las actitudes contemporaneas en este
      espacio ideologico de dos dimensiones. En tanto que la guerra al terror se
      relaciono de manera significativa a la dimension de derecha en todas las
      muestras, las relaciones para el ambientalismo y la ampliacion de la Union
      Europea dependieron de la muestra. Las diferencias interculturales se explican en
      terminos de la notoriedad del tema (relaciones no significativas contra
      significativas en el caso del ambientalismo) y preocupaciones pragmaticas en
      terminos de ganancias y costes (en el caso de la ampliacion de la Union Europea).
      En la discusion, se argumenta tambien que el hecho de que el comunismo penetrara
      en la mentalidad politica con menos exito en Polonia que en la Ucrania podria ser
      la causa de la correspondencia cercana entre la representacion ideologica de
      estas actitudes en Polonia y la de la sociedad occidental. 

PMID- 24274777
TI  - Are Japanese groups more competitive than Japanese individuals? A cross-cultural
      validation of the interindividual-intergroup discontinuity effect.
AB  - The interindividual-intergroup discontinuity effect is the tendency for
      relationships between groups to be more competitive than the relationships
      between individuals. It has been observed robustly in studies conducted in the
      United States, which is a society characterized as "individualistic." In this
      study, it was explored whether the effect was replicable in a "collectivistic"
      society such as Japan. From the traditional view in cross-cultural psychology,
      which emphasizes the collectivistic nature of East Asian peoples, it was expected
      that the discontinuity effect would be greater in Japan than in the United
      States. On the other hand, based on recent empirical findings suggesting that
      North Americans are no less group-oriented than East Asians, it was expected that
      the discontinuity effect would be no greater in Japan than in the United States.
      One hundred and sixty Japanese university students played a 10-trial repeated
      prisoner's dilemma game: 26 sessions of interindividual and 18 sessions of
      intergroup. Following exactly the procedure of prior experiments in the US,
      individuals and groups were allowed face-to-face communication with their
      opponents before making their decisions, and participants in the intergroup
      condition were further allowed to converse freely with their in-group members.
      Results replicated previous findings in the United States; groups made more
      competitive choices than did individuals. In addition, neither the magnitude of
      the discontinuity effect, nor the frequency of competitive choices made by the
      groups, were larger in Japan than they were in the majority of prior studies
      conducted in the United States. These findings suggest cross-cultural robustness
      of the interindividual-intergroup discontinuity effect. Also, interestingly, they
      contradict the simple distinction between individualism and collectivism.
      Implications for studies of culture and group processes are discussed. This
      research was supported by grants from the Center for the Study of Cultural and
      Ecological Foundations of the Mind, a 21(st) Century Center of Excellence Program
      at Hokkaido University. The authors would like to thank Dr. Laura Hernandez
      Guzman, three anonymous reviewers, and Robin Cooper, Mark H. B. Radford, and Paul
      A. Wehr for their helpful comments on earlier versions of this article. They
      would also like to thank Dr. Chester A. Insko for his kind and valuable advice
      during the planning of this experiment as well as the interpretation of its
      results, Kaori Akaishi for her help with data collection, and, finally,
      colleagues at Hokkaido University who helped to recruit potential participants
      from their classes. L'effet de discontinuite entre les individus et entre les
      groupes est la tendance des relations entre les groupes a etre plus competitives
      que les relations entre les individus. Cet effet fut fermement demontre dans des
      etudes menees aux Etats-Unis, une societe caracterisee d' "individualiste". Dans
      la presente etude, nous avons explore dans quelle mesure l'effet etait applicable
      a une societe "collectiviste" comme le Japon. A partir du point de vue
      traditionnel de la psychologie interculturelle, laquelle met l'emphase sur la
      nature collectiviste des peuples de l'Asie de l'Est, il etait attendu que l'effet
      de discontinuite allait etre plus grand au Japon qu'aux Etats-Unis. D'un autre
      cote, se basant sur les donnees empiriques recentes qui suggerent que les Nord
      americains ne sont pas moins orientes vers le groupe que les Asiatiques de l'Est,
      il etait attendu que l'effet de discontinuite ne serait pas plus important au
      Japon qu'aux Etats-Unis. Cent soixante etudiants universitaires japonais ont pris
      part a un jeu de dilemme de prisonnier de 10 essais repetes: 26 sessions entre
      individus et 18 sessions entre groupes. Suivant exactement la procedure des
      experiences menees precedemment aux Etats-Unis, les individus et les groupes
      avaient la permission de communiquer face-a-face avec leur opposant avant de
      prendre leur decision. De plus, les participants de la condition entre groupes
      avaient egalement la possibilite de converser librement avec les membres de leur
      propre groupe. Les resultats se sont reveles semblables a ceux des etudes
      anterieures realisees aux Etats-Unis; les groupes ont fait des choix plus
      competitifs que les individus. En outre, ni la magnitude de l'effet de
      discontinuite, ni la frequence des choix competitifs faits par les groupes
      n'etaient plus grands chez les Japonais comparativement a la majorite des etudes
      anterieures menees aux Etats-Unis. Ces resultats soutiennent la robustesse
      interculturelle de l'effet de discontinuite entre les individus et entre les
      groupes. Aussi, fait interessant, ils contredisent la simple distinction entre
      l'individualisme et le collectivisme. Les implications pour des etudes sur les
      cultures et les processus de groupe sont discutees. El efecto de discontinuidad
      entre individuos y entre grupos es la tendencia a que las relaciones entre grupos
      sean mas competitivas que las relaciones entre individuos. Se ha observado con
      insistencia en estudios conducidos en Estados Unidos, una sociedad caracterizada
      como "individualista". En el presente estudio, se exploro si el efecto se repetia
      en una sociedad "colectivista" como la japonesa. Desde la perspectiva tradicional
      de la psicologia trans cultural, que subraya la naturaleza colectivista de los
      pueblos asiaticos, se esperaba que el efecto de discontinuidad fuese mayor en
      Japon que en Estados Unidos. Por otra parte, con base en los hallazgos empiricos
      recientes que sugieren que los estadounidenses no estan menos orientados al grupo
      que los de este asiatico, se esperaba que el efecto de discontinuidad no fuera
      mayor en Japon que en los Estados Unidos. Ciento sesenta estudiantes
      universitarios japoneses participaron en un juego del dilema de un prisionero de
      diez ensayos repetidos: veintiseis sesiones entre individuos y diez y ocho entre
      grupos. Siguiendo exactamente el procedimiento de los experimentos previos en los
      Estados Unidos, se permitio tanto a los individuos como a los grupos una
      comunicacion cara a cara con sus oponentes antes de tomar sus decisiones, y se
      permitio a los participantes en la condicion entre grupos que conversaran
      libremente con los miembros de su propio grupo. Los resultados repitieron los
      hallazgos previos en los Estados Unidos; los grupos hicieron elecciones mas
      competitivas que los individuos. Ademas, ni la magnitud del efecto de
      discontinuidad ni la frecuencia de las elecciones competitivas de los grupos,
      fueron mayores en Japon que en la mayoria de los estudios previos en Estados
      Unidos. Estos hallazgos sugieren la robustez trans cultural del efecto de
      discontinuidad entre individuos y entre grupos. Tambien, de manera interesante,
      contradicen la simple distincion entre individualismo y colectivismo. Se
      discutieron las implicaciones para los estudios sobre cultura y procesos
      grupales. 

PMID- 24274778
TI  - Parent-adolescent communication in foster, inter-country adoptive, and biological
      Italian families: Gender and generational differences.
AB  - There is a paucity of studies aimed at comparing how parents and children in
      different family structures cope with the challenges posed by the adolescence
      transition; in particular, there are few studies aimed at comparing adoptive and
      foster families. In order to partially fill this gap, the principal aims of the
      present study were to verify whether there are differences in parent-child
      communication among foster, intercountry adoptive, and biological families
      according to the adolescents' gender, and to compare the perceptions of parents
      and adolescents concerning parent-child communication. Data were elaborated on
      two levels: a generational level (adolescent's and his/her parents' perceptions
      among the three family groups) and a dyadic level (mother-child and father-child
      perceptions). The sample was composed of 276 Italian families with adolescents
      aged between 11 and 17 (81 foster, 98 international adoptive, and 97 biological
      families). Subjects (mothers, fathers, and children) filled out a questionnaire
      including the Parent-Adolescent Communication Scale (Barnes & Olson, 1985 ).
      Results highlighted that in foster families, parent-child communication showed
      more difficulties from both the adolescent's and the parents' point of view.
      Adoptive adolescents, however, reported a more positive communication with both
      their parents than did their peers living in biological and foster families. At a
      dyadic level, some differences emerged among the three groups. In biological
      families, a more pronounced distance emerged between parents and children. In
      adoptive families, father and adolescent shared more similar perceptions, whereas
      a significant discrepancy emerged between mother and child. A higher level of
      perceptual congruence between adolescents and parents was found in foster
      families. Gender differences were also seen: Mothers experienced a more open
      communication with their children than did fathers, and adolescents, and above
      all females, communicated better with their mothers than with their fathers in
      all three family groups. Il existe peu d'etudes qui visent a comparer comment les
      parents et les enfants, dans differentes structures familiales, composent avec
      les defis amenes par la transition a l'adolescence; en particulier, il existe peu
      d'etudes qui visent a comparer les familles adoptives et les familles d'accueil.
      Dans le but de combler en partie cette lacune, les principaux buts de la presente
      etude etaient de verifier s'il existe des differences dans la communication
      parent-enfant entre les familles d'accueil, les familles adoptives (adoption
      entre pays) et les familles biologiques en fonction du sexe des adolescents et de
      comparer les perceptions des parents et des adolescents au sujet de la
      communication parent-enfant. Les donnees ont ete elaborees a deux niveaux: un
      niveau generationnel (les perceptions de l'adolescent et de son parent parmi les
      trois groupes familiaux) et un niveau dyadique (perceptions mere-enfant et pere
      enfant). L'echantillon etait compose de 276 familles italiennes avec adolescents
      entre 11 et 17 ans (81 familles d'accueil, 98 familles adoptives internationales
      et 97 familles biologiques). Les participants (meres, peres et enfants) ont
      complete un questionnaire incluant le "Parent-Adolescent Communication Scale
      (Barnes & Olson, 1985 ). Les resultats ont souligne que, dans les familles
      d'accueil, la communication parent-enfant a montre plus de difficultes a la fois
      du point de vue de l'adolescent et du point du parent. Cependant, les adolescents
      adoptifs ont evalue leur communication avec leurs meres et peres comme etant plus
      positive en comparaison a leurs pairs vivant dans des familles d'accueil et dans
      des familles biologiques. A un niveau dyadique, quelques differences ont emerge
      entre les trois groupes. Dans les familles biologiques, une distance plus
      prononcee a emerge entre les parents et les enfants. Dans les familles adoptives,
      le pere et l'adolescent partageaient des perceptions similaires, tandis qu'une
      difference significative a emerge entre la mere et l'enfant. Un plus grand niveau
      de congruence perceptuelle entre les adolescents et les parents a ete trouve dans
      les familles d'accueil. Des differences entre les sexes ont aussi apparu: en
      comparaison aux peres, les meres ont experimente une communication plus ouverte
      avec leurs enfants et les adolescents, surtout les filles, communiquaient mieux
      avec leurs meres qu'avec leurs peres dans les trois groupes familiaux. Son
      escasos los estudios que se han propuesto comparar como los padres e hijos
      pertenecientes a diferentes estructuras familiares afrontan los retos que impone
      la transicion a la adolescencia; en particular, pocos estudios comparan las
      familias adoptivas y las que ejercen el cuidado temporal. Para subsanar
      parcialmente esta deficiencia, los propositos principales de el presente estudio
      fueron verificar si difiere la comunicacion padres-hijos entre familias que
      ejercen cuidado temporal, aquellas adoptivas entre paises, y biologicas de
      acuerdo con el sexo del adolescente, y comparar las percepciones de los padres y
      de los adolescentes en cuanto a la comunicacion padres-hijo. Los datos se
      analizaron en dos niveles: un nivel de generaciones (las percepciones del
      adolescente y de sus padres entre los tres grupos de familias) y un nivel de
      diadas (las percepciones madre-hijo y padre-hijo). Doscientas setenta y seis
      familias italianas con adolescentes entre 11 y 17 anos de edad (81 familias de
      cuidado temporal, 98 adoptivas internacionalmente y 97 biologicas) constituyeron
      la muestra. Los participantes (madres, padres e hijos) respondieron a un
      cuestionario que incluia la Escala de Comunicacion Padre-Adolescente (Barnes &
      Olson, 1985 ). Los resultados resaltan mas dificultades en la comunicacion padres
      hijo en las familias que ejercen cuidado temporal, tanto desde la perspectiva del
      adolescente como de los padres. En tanto que los adolescentes adoptados perciben
      una comunicacion mas positiva que la de sus companeros que viven en familias
      biologicas y de cuidado temporal. En el nivel de diadas, surgieron algunas
      diferencias entre los tres grupos. En las familias biologicas, se observo una
      distancia mas pronunciada entre padres e hijos. En las familias adoptivas, el
      padre y el adolescente comparten percepciones mas similares, mientras que
      discrepan significativamente madre e hijo. Se encontro un nivel mayor de
      congruencia perceptual entre los adolescentes y sus padres en las familias de
      cuidado temporal. En cuanto a diferencias de genero, las madres experimentan una
      comunicacion mas abierta con sus hijos en comparacion con los padres, y los
      adolescentes, sobretodo las mujeres, se comunican mejor con sus madres que con
      sus padres en los tres grupos de familias. 

PMID- 24274779
TI  - Revisiting an era in Germany from the perspective of adolescents in mother-headed
      single-parent families.
AB  - Much of the documented work on families headed by single mothers is based on
      empirical evidence from North America and a few Anglo-Saxon countries. Many
      researchers consider single-mother families to be at a disadvantage because of
      nonsupportive family policies. This paper uses data from a social context that
      differed hugely in this respect-the German Democratic Republic (GDR). The GDR
      provided extensive state support to single-mother families and, thus, was vastly
      different from other countries. Based on a literature review and using Hill's
      family stress theory, this paper is based on the hypothesis that adolescents
      living in mother-headed single-parent families and those living with their
      biological parents would have near-similar social outcomes (display of
      psychosomatic symptoms, perception of stress, display of delinquent behaviour,
      life satisfaction, academic self-efficacy, and academic grades) and family
      related outcomes (relationship with parents and perception of family
      environment). Further, it was hypothesized that adolescents from stepfather
      families would display more negative social and family-related outcomes when
      compared with respondents from the other two family types. The sample comprised
      1302 adolescents (M  =  13.82 years, SD  =  1.88) who were recruited from the
      city of Leipzig in the year immediately following German unification, 1991.
      Respondents reported on measures of psychosomatic symptoms, stress, delinquency,
      life satisfaction, academic achievement, and family-related variables. ANCOVAs,
      with a control for income adjusted for household size, indicated adolescents from
      single-mother families to have very similar experiences to respondents living
      with their biological parents on all measures except for their assessment of
      family environment. Adolescents living in stepfather families reported the least
      favourable experiences. Results are indicative of a social context in Germany
      that, despite unification and the early hardships for single-mother families,
      still provided these families with more opportunities than constraints. This
      paper was completed during a postdoctoral research fellowship from the Alexander
      von Humboldt Foundation awarded to the first author at the Department of
      Developmental Psychology and Centre for Applied Developmental Science, University
      of Jena, Germany. La plupart de la recherche publiee sur les familles dirigees
      par des meres monoparentales est basee sur l'evidence empirique de l'Amerique du
      Nord et de quelques pays anglo-saxons. Plusieurs chercheurs considerent les
      familles de meres monoparentales comme etant desavantagees a cause des politiques
      familiales non supportantes. Cet article utilise des donnees provenant d'un
      contexte social qui differe largement dans ce sens, soit la Republique
      democratique allemande (RDA). La RDA a offert un large soutien de l'etat aux
      familles de meres celibataires et etait ainsi largement differente des autres
      pays. En se fondant sur une recension des ecrits et en utilisant la theorie du
      stress familial de Hill, cet article est base sur l'hypothese que les adolescents
      vivant dans des familles monoparentales dirigees par des meres et ceux vivant
      avec leurs parents biologiques auraient des resultats sociaux (manifestation de
      symptomes psychosomatiques, perception du stress, expression du comportement
      delinquant satisfaction de la vie, auto-efficacite scolaire et notes scolaires)
      et des resultats familiaux (relation avec les parents et perception de
      l'environnement familial) quasi similaires. De plus, nous avons emis l'hypothese
      que les adolescents de familles recomposees avec beau-pere demontreraient plus de
      resultats familiaux et sociaux negatifs, en comparaison aux repondants des deux
      autres types de familles. L'echantillon comprend 1302 adolescents (M = 13.82 ans,
      ecart-type = 1.88) et etait recrute de la ville de Leipzig pendant l'annee qui a
      immediatement suivi l'unification allemande, soit 1991. Les repondants ont
      rapporte sur des mesures de symptomes psychosomatiques, de stress, de
      delinquance, de satisfaction de la vie, de l'accomplissement scolaire et des
      variables reliees a la famille. Des ANCOVAs, en controlant pour le revenu ajuste
      pour la taille du menage, ont indique que les adolescents provenant de familles
      de meres monoparentales ont des experiences tres similaires aux repondants vivant
      avec leurs parents biologiques sur toutes les mesures a l'exception de leur
      evaluation de l'environnement familial. Les adolescents vivant dans des familles
      recomposees avec beau-pere ont rapporte les experiences les moins favorables. Les
      resultats de cette etude devoilent un contexte social en Allemagne qui, malgre
      l'unification du pays et ses difficultes initiales pour les familles de meres
      monoparentales, leur a quand meme offert plus d'opportunites que de contraintes.
      Gran parte de trabajo documentado con familias encabezadas por una madre soltera
      se basa en datos de paises del norte de America y anglo sajones. Muchos
      investigadores consideran a las familias de madre soltera en desventaja, debido a
      politicas que no apoyan a las familias. Este trabajo emplea datos de un contexto
      social diferente, la Republica Democratica Alemana (RDA). La RDA proporciono gran
      apoyo estatal a las familias de madres solteras y, por lo tanto, diferia
      ampliamente de otros paises. Este trabajo, basado en la revision de la literatura
      y empleando la teoria del estres familiar de Hill, propone como hipotesis que
      habria similitud entre los adolescentes que viven en familias de madre soltera y
      aquellos que viven con ambos padres biologicos respecto a desenlaces sociales
      (manifestacion de sintomas psicosomaticos, percepcion de estres, manifestacion de
      conducta delincuente, satisfaccion con la vida, autoeficacia academica, y
      calificaciones escolares) y desenlaces relativos a la familia ( relacion con los
      padres y percepcion del ambiente familiar). Es mas, se propuso la hipotesis de
      que los adolescentes de familias con padrastro manifestarian mas efectos sociales
      y familiares negativos al compararse con adolescentes provenientes de los otros
      dos tipos de familias. La muestra, compuesta por 1302 adolescentes (M = 13.82
      anos, SD = 1.88), se recluto en la ciudad de Leipzig al ano siguiente de la
      unificacion de Alemania, 1991. Los participantes respondieron a medidas de
      sintomas psicosomaticos, estres, delincuencia, satisfaccion por la vida,
      desempeno academico y variables relativas a la familia. Los analisis de
      covarianza aplicados, controlando el ingreso ajustado al tamano de la familia,
      sugirieron que los adolescentes de familias de madre soltera tenian experiencias
      muy similares a las de aquellos que vivian con sus padres biologicos en todas las
      medidas, excepto en la de evaluacion del ambiente familiar. Los adolescentes que
      vivian en familias con padrastro informaron experiencias menos favorables. Los
      resultados son indicativos de que el contexto social en Alemania proporciono aun
      mas oportunidades que restricciones a las familias de madre soltera, a pesar de
      la unificacion y el comienzo de las dificultades que esta les impuso. 

PMID- 24274780
TI  - A review of eating disorders research in Mexico.
AB  - The objective of this paper is to summarize research findings on eating disorders
      and the current state of the field in Mexico. Papers published in indexed
      journals and graduate dissertations were retrieved, using "eating disorders,"
      "anorexia nervosa," "bulimia nervosa," "body image," "binge eating," "restrained
      eating," "weight and shape concern," and "dieting" as keywords. These were
      combined with the Boolean operator "AND" with "Mexico" and "Latin America."
      Findings are presented for epidemiology, the validity of assessment instruments,
      comorbidity, and risk factors. A national representative survey found a
      prevalence of 1.8% for bulimia nervosa, and no cases of anorexia nervosa.
      However, the lack of studies with confirmatory clinical interview and other
      national or regional representative samples makes it difficult to reach
      conclusions about the actual prevalence. A number of instruments for the
      detection of eating disorders and disordered eating have been validated for the
      Mexican population. The comorbidity of eating disorders in Mexico includes drug
      and alcohol abuse, obesity, and borderline personality disorder. Risk factors
      found included body weight and cultural pressure to be thin. Future lines of
      research should include epidemiological studies with representative samples and
      diagnosis confirmation, longitudinal studies, and the exploration of protective
      and risk factors specific to this population. We want to acknowledge Dr Richard
      A. Gordon's encouragement to write this manuscript and his accurate comments on
      its preliminary and final versions. We also want to thank the participants of the
      seminar on publications held at the Office of Epidemiological and Psychosocial
      Studies of the National Institute of Psychiatry for the comments they made to
      this article. El objetivo de este trabajo es el de resumir los hallazgos de
      investigacion sobre los trastornos alimentarios y el estado actual del campo en
      Mexico. Se recupero la obra publicada en revistas indizadas y tesis de grado,
      mediante los descriptores "trastorno alimentario," anorexia nervosa," bulimia
      nervosa," "imagen corporal," "atracones," "restriccion alimentaria,"
      "preocupacion por el peso y la figura," y "conducta de dieta." Estos se
      combinaron con el operador Booleano "AND" con "Mexico" y "America Latina." Se
      presentan los hallazgos para la epidemiologia, la validez de los instrumentos de
      medicion, comorbilidad, y factores de riesgo. Una encuesta nacional
      representativa encontro una prevalencia de 1.8% para la bulimia nervosa, y ningun
      caso de anorexia nervosa. No obstante, la carencia de estudios con una entrevista
      clinica confirmatoria y de otras muestras nacionales o regionales dificulta el
      arribo a conclusiones acerca de la prevalencia real. Varios instrumentos para la
      deteccion de los trastornos alimentarios y de la alimentacion desordenada se han
      validado en poblacion mexicana. La comorbilidad de los trastornos alimentarios en
      Mexico incluye el uso y abuso de alcohol, la obesidad y el trastorno de
      personalidad limitrofe. Los factores de riesgo referidos incluyen el peso
      corporal y la presion cultural para estar delgado. Las lineas de investigacion
      futuras deberan incluir estudios epidemiologicos con muestras representativas y
      la confirmacion del diagnostico, estudios longitudinales, y la exploracion de
      factores de riesgo y protectores especificos a esta poblacion. L'objectif de cet
      article est de resumer les resultats de recherche et l'etat actuel des
      connaissances sur les troubles alimentaires au Mexique. Les articles publies dans
      des revues indexees et les theses de doctorat ont ete recenses en utilisant les
      mots-cles " eating disorders ", " anorexia nervosa ", " bulimia nervosa ", " body
      image ", " binge eating ", " restrained eating ", " weight and shape concern " et
      " dieting ". Ceux-ci furent combines, en utilisant la conjonction " AND ", avec
      les termes " Mexico " et " Latin America ". Les resultats sont presentes de facon
      a decrire l'epidemiologie, la validite des instruments d'evaluation, la
      comorbidite et les facteurs de risque. Une enquete normative nationale a indique
      un taux de prevalence de 1,8% pour la nevrose boulimique et aucun cas de nevrose
      anorexique. Cependant, le manque d'etudes utilisant des entrevues cliniques
      confirmatoires et d'autres echantillons normatifs nationaux et regionaux limite
      les conclusions sur la prevalence actuelle. Un nombre important d'instruments
      pour depister les troubles alimentaires et l'alimentation inadequate ont ete
      valides aupres de la population mexicaine. Les principaux problemes de
      comorbidite avec les troubles alimentaires au Mexique incluent l'abus de drogue
      ou d'alcool, l'obesite et le trouble de personnalite etat-limite. Les facteurs de
      risque incluent le poids corporel et la pression culturelle a etre mince. Les
      avenues de recherche futures devraient inclure des etudes epidemiologiques aupres
      d'echantillons representatifs, de la confirmation de diagnostic, des etudes
      longitudinales et de l'exploration de facteurs de protection et de facteurs de
      risque specifiques a cette population. 

PMID- 24274781
TI  - Corrigendum.

PMID- 24274782
TI  - Acne vulgaris in preadolescent children: recommendations for evaluation.
AB  - Acne vulgaris in infants and children often triggers extensive laboratory
      evaluation out of concern about associated endocrinopathy. Clinical parameters to
      help guide evaluation of these children have not been defined. This was a
      retrospective chart review of 24 preadolescent patients with acne and a review of
      related medical literature. Two age-related subsets were identified: 12 patients
      who developed acne before the age of 15 months, 75% male, with comedonal and
      inflammatory lesions; and 12 patients who developed acne between the ages of 2
      and 7 years, 75% female, with primarily comedonal lesions. Laboratory evaluation
      in 13 of the patients was unremarkable. Bone age was advanced in 1 of the 11
      children imaged. Premature adrenarche was diagnosed in four patients; all four
      had additional clinical signs of puberty and growth parameters >90th percentile.
      None required additional treatment. Our cohort of preadolescent children
      presenting with acne included an equal number of patients in two distinct
      subsets: infantile and childhood-onset acne. Literature review identified a rare
      third subset presenting with acne, signs of advanced puberty, and associated
      endocrinopathy. There was no evidence of endocrinopathy in our patients with
      infantile acne. Two-thirds of our patients with childhood-onset acne had no
      additional clinical signs of puberty and no evidence of endocrinopathy. A focused
      history and physical examination is sufficient to evaluate the majority of
      infants and children with acne. Hand X-ray for bone age is a useful screening
      test. Further evaluation and endocrinology referral are warranted in
      preadolescents with acne and advanced bone age or additional clinical evidence of
      early puberty.

PMID- 24274783
TI  - Myocarditis after trimethoprim/sulfamethoxazole treatment for ehrlichiosis.
AB  - The manifestations of human monocytic ehrlichiosis range from a mild febrile
      syndrome to a severe multisystem illness. Myocardial involvement is uncommon. We
      report a woman, 78 years of age, who was treated with
      trimethoprim/sulfamethoxazole after a tick bite, in whom myocarditis was
      subsequently diagnosed. She recovered completely after doxycycline therapy. 

PMID- 24274784
TI  - The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical
      recurrence in intermediate-risk prostate cancer treated with external beam
      radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.
AB  - OBJECTIVE: To study the prognostic value of the University of California, San
      Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict
      biochemical failure (bF) after various doses of external beam radiotherapy (EBRT)
      and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). PATIENTS
      AND METHODS: We retrospectively analysed 345 patients with intermediate-risk
      prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244
      EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum
      follow-up was 3 years. No patient received primary androgen-deprivation therapy.
      bF was defined according to the Phoenix definition. Cox regression analysis was
      used to estimate the differences between CAPRA groups. RESULTS: The overall bF
      rate was 13% (45/345). The CAPRA score, as a continuous variable, was
      statistically significant in multivariate analysis for predicting bF (hazard
      ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a
      trend for a lower bF rate in patients treated with LDR PB when compared with
      those treated by EBRT <= 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in
      multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5,
      CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01
      2.27, P = 0.047) in multivariate analysis. CONCLUSION: The CAPRA score is useful
      for predicting biochemical recurrence in patients treated for intermediate-risk
      prostate cancer with EBRT or LDR PB. It could help in treatment decisions.

PMID- 24274785
TI  - Oxidation states, geometries, and electronic structures of plutonium tetroxide
      PuO4 isomers: is octavalent Pu viable?
AB  - In neutral chemical compounds, the highest known oxidation state of all elements
      in the Periodic Table is +VIII. While PuO4 is viewed as an exotic Pu(+VIII)
      complex, we have shown here that no stable electronic homologue of octavalent
      RuO4 and OsO4 exists for PuO4, even though Pu has the same number of eight
      valence electrons as Ru and Os. Using quantum chemical approaches at the levels
      of quasi-relativistic DFT, MP2, CCSD(T), and CASPT2, we find the ground state of
      PuO4 as a quintet (5)C2v-(PuO2)(+)(O2)(-) complex with the leading valence
      configuration of an (f(3))plutonyl(V) unit, loosely coupled to a superoxido
      (pi*(3))O2(-) ligand. This stable isomer is likely detectable as a transient
      species, while the previously suggested planar (1)D4h-Pu(VIII)O4 isomer is only
      metastable. Through electronic structure analyses, the bonding and the oxidation
      states are explained and rationalized. We have predicted the characteristics of
      the electronic and vibrational spectra to assist future experimental
      identification of (PuO2)(+)(O2)(-) by IR, UV-vis, and ionization spectroscopy. 

PMID- 24274786
TI  - Pediatric invasive streptococcal infection in northern and eastern regions of
      Hokkaido, Japan from 2010 to 2012.
AB  - BACKGROUND: The frequency of occurrence of pediatric invasive streptococcal
      infection in Japan has not been studied, therefore the aim of this study was to
      survey the northern and eastern regions of Hokkaido from 2010 to 2012. METHOD:
      Survey sheets were sent to the pediatric departments at 17 facilities where
      children in the subject region can be hospitalized. Responses were obtained from
      all of the 17 facilities. RESULTS: Seven patients developed group A streptococcal
      infection over the 3 years, and their ages ranged from 1 day after the birth to
      15 years old. Sepsis was diagnosed in five children, and empyema and arthritis in
      the knee were found in one child each, respectively. The number of cases in
      children under 15 years old was six excluding the child who was 15 years old, and
      the incidence rate per 100,000 population was 1.00. Eight children developed
      group B streptococcal infection, and their ages ranged from 0 days to 2 months
      after birth. Two cases were the early onset type (age within 7 days) and six
      cases were the late onset type. Five children developed sepsis and three children
      developed meningitis. The frequency of occurrence was 0.24 per 1000 births; which
      was 0.06 per 1000 births for the early onset type and was 0.18 per 1000 births
      for the late onset type. No reports for group C or group G hemolytic
      streptococcal infection were obtained. CONCLUSIONS: The incidence rates
      identified in the present survey are similar to those in other advanced
      countries, and appear to be valid.

PMID- 24274787
TI  - Vaccinia virus in household environment during bovine vaccinia outbreak, Brazil.

PMID- 24274788
TI  - Subcellular targeting of proteins and pathways during evolution.

PMID- 24274790
TI  - Nutrient responses to ecosystem disturbances from annual to multi-millennial
      timescales.

PMID- 24274789
TI  - Unseen sex in ancient virgin fungi.

PMID- 24274791
TI  - Two new triterpenoids from Ampelopsis japonica (Thunb.) Makino.
AB  - Two new triterpenoids were isolated from the ethanolic extract of the roots of
      Ampelopsis japonica (Thunb.) Makino. Their structures were defined as 3alpha
      trans-feruloyloxy-2alpha-O-acetylurs-12-en-28-oic acid (1) and methyl 3alpha
      trans-feruloyloxy-2alpha-hydroxyurs-12-en-28-oate (2) on the basis of spectral
      analysis. 

PMID- 24274792
TI  - Band structure engineering in topological insulator based heterostructures.
AB  - The ability to engineer an electronic band structure of topological insulators
      would allow the production of topological materials with tailor-made properties.
      Using ab initio calculations, we show a promising way to control the conducting
      surface state in topological insulator based heterostructures representing an
      insulator ultrathin films on the topological insulator substrates. Because of a
      specific relation between work functions and band gaps of the topological
      insulator substrate and the insulator ultrathin film overlayer, a sizable shift
      of the Dirac point occurs resulting in a significant increase in the number of
      the topological surface state charge carriers as compared to that of the
      substrate itself. Such an effect can also be realized by applying the external
      electric field that allows a gradual tuning of the topological surface state. A
      simultaneous use of both approaches makes it possible to obtain a topological
      insulator based heterostructure with a highly tunable topological surface state. 

PMID- 24274794
TI  - Cyclization of squalene from both termini: identification of an onoceroid
      synthase and enzymatic synthesis of ambrein.
AB  - The onoceroids are triterpenoids biosynthesized from squalene or (3S)-2,3
      oxidosqualene by cyclization from both termini. We recently revealed that
      tetraprenyl-beta-curcumene cyclase from Bacillus megaterium (BmeTC) is a
      bifunctional triterpene/sesquarterpene cyclase that converts head-to-tail
      tetraprenyl-beta-curcumene and tail-to-tail squalene into pentacyclic and
      bicyclic products, respectively, in vivo. Here, we reveal that BmeTC has an
      unprecedented catalytic function in cyclizing squalene from both termini and is
      the first onoceroid synthase. We also report the first onoceroids from bacterial
      origin. Our discoveries suggest that symmetric and asymmetric onoceroids could be
      biosynthesized by a single enzyme via an intermediate cyclized at one terminus of
      squalene. Furthermore, the new function of BmeTC enabled the synthesis of (+)
      ambrein, a major constituent of ambergris that is difficult to obtain naturally,
      via a mutated squalene-hopene cyclase-catalyzed reaction from easily available
      squalene. 

PMID- 24274793
TI  - Spirometry and health status worsen with weight gain in obese smokers but improve
      in normal-weight smokers.
AB  - RATIONALE: The literature on the effect of obesity and weight gain on respiratory
      outcomes in smokers is contradictory. OBJECTIVE: To examine the cross-sectional
      effect of body mass index (BMI) and the longitudinal effect of change in BMI upon
      spirometry and health status among smokers at risk for and with milder chronic
      obstructive pulmonary disease (COPD). METHODS: Participants from the Lovelace
      Smokers' Cohort were followed for a median period of 6 years, 75% of whom were at
      risk and 25% of whom had COPD at baseline examination. BMI and gain in BMI were
      examined as continuous independent variables overall and after stratification
      into three categories (normal-weight, overweight, and obese) determined on the
      basis of baseline weight. Spirometry and health status (as assessed by St. George
      Respiratory Questionnaire total and subscale scores) were dependent variables.
      Covariates included age, sex, ethnicity, pack-years of smoking, and current
      smoking status. Cross-sectional analysis used linear and logistic regression;
      longitudinal analysis used a mixed model approach. MEASUREMENTS AND MAIN RESULTS:
      In cross-sectional analyses, higher BMI was associated with worse health status
      among obese smokers but with better health status among normal-weight smokers. In
      longitudinal analyses, weight gain was associated with a decrease in FEV1 and
      health status among obese smokers and with an increase in these outcomes among
      normal-weight smokers. CONCLUSIONS: Weight gain affects respiratory outcomes
      differently between obese and normal-weight smokers. Whereas FEV1 and health
      status decrease with weight gain among obese smokers, they improve among normal
      weight smokers. The nonlinear relationship between weight gain and respiratory
      outcomes suggests that this effect of excess weight is unlikely to be mechanical
      alone.

PMID- 24274795
TI  - Structure-plant growth inhibitory activity relationship of lariciresinol.
AB  - The syntheses of 55 lariciresinol derivatives containing derivatives on the 9
      position and an aryl group at both 7- and 7'-positions were successful to examine
      the effect of structure of (-)-lariciresinol (1) on plant growth regulatory
      activity. (-)-(7R,8R,8'S)-9-Dehydroxylariciresinol 9 showed activity 2-fold more
      potent than that of natural (-)-lariciresinol (1) and -95% growth inhibitory
      activity to negative control against rye grass root at 1 mM. The derivatives
      bearing hydrophobic and smaller groups at the 9-position showed higher activity.
      The importance of 4- and 4'-hydroxy groups and 3- and 3'-small hydrophobic groups
      on 7- and 7'-phenyl groups for higher activity was also suggested. 

PMID- 24274796
TI  - Space-weathering of solar system bodies: a laboratory perspective.

PMID- 24274797
TI  - Identification and prediction of group-based glycemic control trajectories during
      the transition to adolescence.
AB  - OBJECTIVE: To identify trajectories of glycemic control over a period of 3 years
      in a pediatric sample of youth diagnosed with Type 1 diabetes transitioning to
      adolescence. A second aim was to examine a set of modifiable individual and
      family level baseline predictors of glycemic control group membership. METHODS:
      This multisite, prospective study included 239 children and adolescents (ages 9
      11 years at baseline) diagnosed with Type 1 diabetes and their caregivers.
      Glycemic control was based on hemoglobin A1c (HbA1c) collected at 6-month
      intervals over a period of 3 years. Predictors of glycemic control membership
      included baseline global executive functioning, diabetes self-management,
      diabetes-specific family conflict, blood glucose monitoring frequency, and
      relevant individual and family level covariates. RESULTS: Group-based trajectory
      analyses were used to describe patterns of glycemic control from baseline to 36
      months and 3 trajectories were identified: low risk (42.9%), elevated risk
      (44.6%), and high risk (12.1%) subgroups. Baseline maternal-reported family
      conflict, blood glucose monitoring frequency, and gender were significant
      predictors of glycemic control group membership. Higher levels of baseline family
      conflict, lower frequency of blood glucose monitoring, and female gender were
      associated with elevated and high-risk group membership. CONCLUSIONS: These
      findings underscore the importance of examining trajectories of HbA1c across
      time. These results suggest that problematic trajectories of glycemic control are
      evident during the transition to adolescence. Furthermore, there are modifiable
      individual and family level characteristics that predict group membership and
      hence could be targeted in interventions to ensure adequate glycemic control is
      maintained over time and that risks for diabetes-related complications are
      reduced.

PMID- 24274798
TI  - Harnessing benefits of helping others: a randomized controlled trial testing
      expressive helping to address survivorship problems after hematopoietic stem cell
      transplant.
AB  - OBJECTIVE: Prior research supports the hypothesis that cancer survivors who help
      others face treatment experience a range of psychosocial and health-related
      benefits as a result of peer helping. This study investigates an expressive
      helping (EH) intervention designed to harness those benefits by targeting
      survivorship problems among cancer survivors treated with hematopoietic stem cell
      transplant. EH includes two components: (a) emotionally expressive writing (EW;
      writing one's deepest thoughts and feelings about the transplant experience in a
      series of brief, structured writing sessions) followed by (b) peer helping (PH;
      helping other people prepare for transplant by sharing one's own transplant
      experiences along with advice and encouragement through a written narrative).
      METHOD: EH was compared with neutral writing (NW), EW (without PH), and PH
      (without EW) in a 4-arm randomized controlled trial in which survivors completed
      baseline measures, 4 structured writing exercises (with instructions depending on
      randomization), and postintervention measures including validated measures of
      general psychological distress, physical symptoms, and health-related quality of
      life (HRQOL). RESULTS: Among survivors with moderate-severe survivorship
      problems, EH reduced distress (compared with NW and PH; ps < .05) and improved
      physical symptoms (compared with NW, PH, and EW; ps < .002) and HRQOL (compared
      with NW; p = .02). CONCLUSIONS: Peer helping through writing benefits transplant
      survivors with moderate-severe survivorship problems, but only if they have first
      completed expressive writing.

PMID- 24274799
TI  - The power of positive and negative expectations to influence reported symptoms
      and mood during exposure to wind farm sound.
AB  - OBJECTIVE: Wind farm developments have been hampered by claims that sound from
      wind turbines causes symptoms and negative health reports in nearby residents. As
      scientific reviews have failed to identify a plausible link between wind turbine
      sound and health effects, psychological expectations have been proposed as an
      explanation for health complaints. Building on recent work showing negative
      expectations can create symptoms from wind turbines, we investigated whether
      positive expectations can produce the opposite effect, in terms of a reduction in
      symptoms and improvements in reported health. METHOD: 60 participants were
      randomized to either positive or negative expectation groups and subsequently
      exposed to audible wind farm sound and infrasound. Prior to exposure, negative
      expectation participants watched a DVD incorporating TV footage about health
      effects said to be caused by infrasound produced by wind turbines. In contrast,
      positive expectation participants viewed a DVD that outlined the possible
      therapeutic effects of infrasound exposure. RESULTS: During exposure to audible
      windfarm sound and infrasound, symptoms and mood were strongly influenced by the
      type of expectations. Negative expectation participants experienced a significant
      increase in symptoms and a significant deterioration in mood, while positive
      expectation participants reported a significant decrease in symptoms and a
      significant improvement in mood. CONCLUSION: The study demonstrates that
      expectations can influence symptom and mood reports in both positive and negative
      directions. The results suggest that if expectations about infrasound are framed
      in more neutral or benign ways, then it is likely reports of symptoms or negative
      effects could be nullified.

PMID- 24274800
TI  - Symptom dimensions of anxiety following myocardial infarction: associations with
      depressive symptoms and prognosis.
AB  - OBJECTIVE: Differential associations of symptom dimensions with prognosis in
      myocardial infarction (MI) patients have been shown for depression, but no
      studies have focused on anxiety dimensions. The aim of this study was to assess
      the association between somatic and psychological symptoms of anxiety following
      acute MI with adverse prognosis and to assess the overlap between anxiety and
      depression dimensions. METHOD: Patients (n = 418) were assessed on demographic
      and clinical variables. The Hamilton Anxiety and Depression Rating Scales were
      used to measure anxiety and depression 2 months post-MI. Mean follow-up period
      was 3.8 years and the endpoint consisted of all-cause mortality and recurrent MI.
      RESULTS: After adjustment for demographic and clinical variables, somatic anxiety
      was significantly associated with recurrent MI and mortality (HR: 1.32; 95% CI
      [1.03, 1.69]; p = .03), and a trend was shown for an association between
      psychological anxiety and outcome (HR: 1.29; 95% CI [0.99, 1.67]; p = .06). The
      total anxiety score of the HARS was the strongest predictor of recurrent MI and
      mortality (HR: 1.38; 95% CI [1.07, 1.78]; p = .02). The HARS and the HDRS were
      highly correlated (r = .86; p < .01). Dimensions consisting of psychological
      distress (HR: 1.29; 95% CI [1.02, 1.63]; p = .03) and cardiopulmonary/autonomic
      symptoms (HR: 1.36; 95% CI [1.06, 1.75]; p = .02) also predicted outcome in
      adjusted analyses. CONCLUSIONS: Anxiety was associated with adverse prognosis in
      MI patients with significant associations for somatic anxiety and total anxiety.
      When combining anxiety and depression items, psychological distress and
      cardiopulmonary/autonomic symptoms predicted recurrent MI and mortality. Future
      research might better focus on dimensions of anxiety and depression
      simultaneously in MI patients.

PMID- 24274801
TI  - Response rates in studies of couples coping with cancer: a systematic review.
AB  - OBJECTIVE: Recruiting couples for psychological studies can be challenging. This
      brief report is the first to examine the average couples' response rate and to
      systematically review the quality of reporting of couples' response rate in
      studies of couples coping with cancer. METHOD: A systematic review (1980-2011)
      was conducted, including 83 studies meeting the inclusion criteria of being
      published in peer-reviewed journals, describing quantitative findings using a
      cross-sectional or longitudinal design. RESULTS: Overall reporting was
      unsatisfactory in more than half of the included studies. As a consequence, the
      couples' response rate (CRR; all analyzed couples divided by the number of
      eligible partnered patients/couples approached) could be calculated for only 33
      samples. This CRR varied considerably across studies from 25% to 90% (CRRM = 58%,
      SD = 17%). The rates reported in the articles (M = 65%) were often higher than
      the average CRR (CRRM = 57%) of these samples. CONCLUSIONS: This systematic
      review revealed incomplete reporting of response rate. Therefore, it cannot be
      firmly concluded that the average CRR reported is representative for all studies
      on couples coping with cancer. Finally, the figures presented, which are often
      more favorable than the CRR, may create the impression that the sample is more
      representative of the target population than it actually is. This has
      consequences for implementing the findings of such studies into practice. The
      results are critically discussed, and recommendations for improvement are
      provided.

PMID- 24274802
TI  - Combinations of techniques that effectively change health behavior: evidence from
      Meta-CART analysis.
AB  - OBJECTIVE: Many health-promoting interventions combine multiple behavior change
      techniques (BCTs) to maximize effectiveness. Although, in theory, BCTs can
      amplify each other, the available meta-analyses have not been able to identify
      specific combinations of techniques that provide synergistic effects. This study
      overcomes some of the shortcomings in the current methodology by applying
      classification and regression trees (CART) to meta-analytic data in a special
      way, referred to as Meta-CART. The aim was to identify particular combinations of
      BCTs that explain intervention success. METHOD: A reanalysis of data from Michie,
      Abraham, Whittington, McAteer, and Gupta (2009) was performed. These data
      included effect sizes from 122 interventions targeted at physical activity and
      healthy eating, and the coding of the interventions into 26 BCTs. A CART analysis
      was performed using the BCTs as predictors and treatment success (i.e., effect
      size) as outcome. A subgroup meta-analysis using a mixed effects model was
      performed to compare the treatment effect in the subgroups found by CART.
      RESULTS: Meta-CART identified the following most effective combinations: Provide
      information about behavior-health link with Prompt intention formation (mean
      effect size g = 0.46), and Provide information about behavior-health link with
      Provide information on consequences and Use of follow-up prompts (g = 0.44).
      Least effective interventions were those using Provide feedback on performance
      without using Provide instruction (g = 0.05). CONCLUSIONS: Specific combinations
      of BCTs increase the likelihood of achieving change in health behavior, whereas
      other combinations decrease this likelihood. Meta-CART successfully identified
      these combinations and thus provides a viable methodology in the context of meta
      analysis.

PMID- 24274803
TI  - Offspring of a parent with genetic disease: childhood experiences and adult
      psychological characteristics.
AB  - OBJECTIVE: To investigate childhood experiences and psychological characteristics
      in offspring of a parent with genetic disease. METHOD: Self-report scales were
      used to assess adverse childhood experiences (ACEs), adult attachment style,
      mental health, and psychological symptomatology in offspring of a parent with a
      neurogenetic disorder (i.e. Huntington's Disease, HD; Cerebral Autosomal Dominant
      Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL; and
      Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type, HCHWA-D), and in
      offspring of a parent affected with Hereditary Breast/Ovarian Cancer (HBOC).
      These groups were compared to persons who did not have a parent with one of these
      genetic diseases. Associations between childhood experiences and adult
      psychological characteristics were investigated. RESULTS: Compared with the
      reference group (n = 127), offspring of a parent with a neurogenetic disorder (n
      = 96) reported more parental dysfunction in childhood, and showed more adult
      attachment anxiety and poorer mental health. Offspring of a parent with HBOC (n =
      70) reported more parental loss in childhood and showed poorer mental health.
      Offspring who experienced parental genetic disease in childhood had more
      attachment anxiety than offspring who experienced parental disease later in life.
      In the group of offspring, a higher number of ACEs was associated with poorer
      mental health and more psychological symptomatology. CONCLUSIONS: This cross
      sectional study indicates that adult offspring of a parent with genetic disease
      may differ in attachment style and mental health from persons without one of
      these genetic diseases in their family, and that this may be related to adverse
      childhood experiences.

PMID- 24274804
TI  - A comparison of correlates associated with adult physical activity behavior in
      major cities and regional settings.
AB  - OBJECTIVE: People living outside of urban areas are at higher risk for physical
      inactivity. Understanding physical activity correlates in different settings is
      important for understanding this risk. This study compared psychological,
      demographic, and health-related correlates of activity among adults living in
      major cities (urban areas) and regional (low-population density) towns and
      whether there were significant differences in how these potential determinants
      related to physical activity. METHODS: Participants (n = 756) were male and
      female adults who were members of the Australian Health and Social Science panel.
      Participant characteristics and physical activity were assessed using
      standardized measures via an online survey. Differences in the strength of the
      relation between the physical activity correlates were tested using equality of
      regression coefficient tests. RESULTS: Few differences in physical activity
      determinants between major cities and regional settings were observed. For major
      city and regional areas, self-efficacy and outcome expectations were the most
      strongly related correlates to physical activity. The strength of associations
      between the correlates and physical activity did not differ between areas, with
      the exception of working status. Not working was associated with lower odds of
      meeting physical activity guidelines for major city residents but not for
      regional residents. CONCLUSION: Physical activity correlates were generally
      similar for people living in major city and regional areas. This suggests that
      physical activity interventions targeting personal factors do not need to tailor
      to a person's level of urbanization. Studies examining the interaction between
      psychological correlates of physical activity and environmental factors are
      needed.

PMID- 24274805
TI  - Childhood cumulative risk and later allostatic load: mediating role of substance
      use.
AB  - OBJECTIVE: The present study investigated the long-term impact of exposure to
      poverty-related stressors during childhood on allostatic load, an index of
      physiological dysregulation, and the potential mediating role of substance use.
      METHOD: Participants (n = 162) were rural children from New York State, followed
      for 8 years (between the ages 9 and 17). Poverty- related stress was computed
      using the cumulative risk approach, assessing stressors across 9 domains,
      including environmental, psychosocial, and demographic factors. Allostatic load
      captured a range of physiological responses, including cardiovascular,
      hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, and
      metabolic activity. Smoking and alcohol/drug use were tested as mediators of the
      hypothesized childhood risk-adolescent allostatic load relationship. RESULTS:
      Cumulative risk exposure at age 9 predicted increases in allostatic load 8 years
      later. Smoking, but not alcohol and drug use, was a significant mediator of the
      prospective, longitudinal relationship between childhood cumulative risk and
      adolescent allostatic load. CONCLUSIONS: The present paper contributes to the
      understanding of the role of early life stress in health across the life span and
      of the mechanisms by which adverse childhood environments impact health as
      children emerge into early adulthood. This knowledge will have implications for
      early intervention efforts.

PMID- 24274806
TI  - Coaction in multiple behavior change interventions: consistency across multiple
      studies on weight management and obesity prevention.
AB  - OBJECTIVE: Coaction refers to the extent to which taking action on one behavior
      increases the odds of taking action on a second behavior. This integrative study
      examines the generalization of coaction in three studies on weight-related
      behaviors. METHOD: Data from three randomized trials of tailored interventions (n
      = 1,277, n = 1,800, and n = 6,000) were examined to determine if coaction of
      behavior change occurred differentially in treatment and control groups. In each
      analysis, the likelihood of progressing to the Action or Maintenance stages for
      the target behaviors was evaluated using logistic regression. RESULTS: Despite
      differences in populations, targeted behaviors, levels of tailoring in
      interventions, and timing of follow-up assessments, 17 out of 24 (70.8%) logistic
      regressions revealed significant coaction in the treatment group as opposed to
      only three out of 24 (12.5%) in the control condition. In 23/24 analyses,
      coaction of behavior change was larger on an absolute basis in the treatment
      group. Individuals in the treatment group progressing to Action/Maintenance for
      one behavior were 1.4-5 times more likely to make progress on another behavior
      compared to those in the treatment group who did not make such progress on the
      first behavior. CONCLUSIONS: This study demonstrates that despite considerable
      variability in study design, coaction reliably occurs more in the presence of
      Transtheoretical-Model based multiple behavior change interventions. Additional
      studies are needed to replicate these results in other behavioral areas and to
      examine the predictors of differential coaction. The ability to consistently
      create coaction within multiple behavior interventions can increase the efficacy
      and cost-effectiveness of multiple behavior change interventions.

PMID- 24274807
TI  - Social oppression, psychological vulnerability, and unprotected intercourse among
      young Black men who have sex with men.
AB  - OBJECTIVE: Young Black men who have sex with men (YBMSM) are at extraordinarily
      high risk for HIV infection. Given their dual minority identity, they experience
      multiple forms of social oppression-racism, homophobia, and poverty. This study
      tested a model for how these forces contribute to their sexual risk behavior.
      METHOD: YBMSM (n = 1,289) from 2 Texas cities completed a 1-time assessment of
      sexual behaviors and psychosocial variables. Structural equation modeling was
      used to characterize relationships among variables. RESULTS: Experiences of
      racism, homophobia, and socioeconomic distress were all associated with
      unprotected anal intercourse (UAI) either directly or indirectly in a manner
      largely consistent with Diaz's (1997, 1998) model of the effects of social
      oppression. Racism, homophobia, and socioeconomic distress were each associated
      with specific psychological vulnerabilities, which were in turn associated with
      participation in difficult sexual situations (e.g., in a public setting), and
      then UAI. The effects of racism were largely mediated by depressive symptoms and
      participation in difficult sexual situations. Homophobia was mediated by
      depressive symptoms, social support, and internalized homophobia. The effects of
      socioeconomic distress were partially mediated by decreased social support and
      greater participation in difficult sexual situations. Socioeconomic distress also
      had a significant direct effect on UAI not explained by the proposed mediators.
      CONCLUSIONS: Social oppression contributes to YBMSM's psychological
      vulnerabilities, participation in difficult sexual situations, and their UAI.
      Interventions to reduce sexual risk in YBMSM should address socioeconomic
      disadvantage, homophobia, and racism, as well as the psychological challenges
      that social oppression creates for them.

PMID- 24274808
TI  - Online prostate cancer screening decision aid for at-risk men: a randomized
      trial.
AB  - OBJECTIVE: This study examines the efficacy of an online screening decision aid
      (DA) for men with a family history of prostate cancer. METHODS: Unaffected
      Australian men (40-79 years) with at least one affected relative completed the
      first online questionnaire, were randomized to read either the tailored DA
      (intervention) or nontailored information about prostate cancer screening
      (control), then completed a questionnaire postreading and 12 months later. The
      primary outcome was decisional conflict regarding prostate specific antigen (PSA)
      testing. The impact of the DA on longitudinal outcomes was analyzed by using
      random intercept mixed effects models. Logistic and linear regressions were used
      to analyze the impact of the DA on screening behavior and decision regret. Stage
      of decision-making was tested as a moderator for decisional conflict and decision
      regret. The frequency of online material access was recorded. RESULTS: The DA had
      no effect on decisional conflict, knowledge, inclination toward PSA testing,
      accuracy of perceived risk, or screening behavior. However, among men considering
      PSA testing, those who read the DA had lower decision regret compared with men
      who read the control materials, beta = 0.34, p < .001, 95% confidence interval
      (CI) = [.22, .53]. CONCLUSIONS: This is the first study to our knowledge to
      evaluate the uptake and efficacy of an online screening DA among men with a
      family history of prostate cancer. Men who were undecided about screening at
      baseline benefitted from the DA, experiencing less regret 12 months later. In
      relation to decisional conflict, the control materials may have operated as a
      less complex and equally informative DA.

PMID- 24274809
TI  - Simplified quantitative glycomics using the stable isotope label Girard's reagent
      p by electrospray ionization mass spectrometry.
AB  - Fast, sensitive, and simple methods for quantitative analysis of disparities in
      glycan expression between different biological samples are essential for studies
      of protein glycosylation patterns (glycomics) and the search for disease glycan
      biomarkers. Relative quantitation of glycans based on stable isotope labeling
      combined with mass spectrometric detection represents an emerging and promising
      technique. However, this technique is undermined by the complexity of mass
      spectra of isotope-labeled glycans caused by the presence of multiple metal ion
      adduct signals, which result in a decrease of detection sensitivity and an
      increase of difficulties in data interpretation. Herein we report a simplified
      quantitative glycomics strategy, which features nonreductive isotopic labeling of
      reducing glycans with either nondeuterated (d0-) or deuterated (d5-) Girard's
      reagent P (GP) without salts introduced and simplified mass spectrometric
      profiles of d0- and d5-GP derivatives of neutral glycans as molecular ions
      without complex metal ion adducts, allowing rapid and sensitive quantitative
      comparison between different glycan samples. We have obtained optimized GP
      labeling conditions and good quantitation linearity, reproducibility, and
      accuracy of data by the method. Its excellent applicability was validated by
      comparatively quantitative analysis of the neutral N-glycans released from bovine
      and porcine immunoglobulin G as well as of those from mouse and rat sera.
      Additionally, we have revealed the potential of this strategy for the high
      sensitivity analysis of sialylated glycans as GP derivatives, which involves
      neutralization of the carboxyl group of sialic acid by chemical derivatization. 

PMID- 24274810
TI  - Fluorescence quenching of carbon nitride nanosheet through its interaction with
      DNA for versatile fluorescence sensing.
AB  - This work investigates the interaction of carbon nitride nanosheet (CNNS), a
      recently developed two-dimensional nanomaterial, with DNA and its fluorescence
      quenching mechanism on fluorophore labeled single-stranded DNA probes. The static
      quenching through the photoinduced electron transfer (PET) from the excited
      fluorophore to the conductive band of CNNS is identified. Utilizing the affinity
      change of CNNS to DNA probes upon their recognition to targets and the PET-based
      fluorescence quenching effect, a universal sensing strategy is proposed for
      design of several homogeneous fluorescence detection methods with short assay
      time and high sensitivity. This strategy is versatile and can be combined with
      different amplification tools for quick fluorescence sensing of DNA and extensive
      DNA related analytes such as metal cations, small molecules, and proteins. As
      examples, two simple fluorescence detection methods for DNA and Hg(2+), one
      facile detection method coupled with Exo III-mediated target recycling for
      sensitive DNA analysis, and a ratiometric fluorescence protocol for DNA detection
      are proposed. This work provides an avenue for understanding the interaction
      between two-dimensional nanomaterials and biomolecules and designing novel
      sensing strategies for extending the applications of nanomaterials in
      bioanalysis. 

PMID- 24274811
TI  - The zoonotic potential of daptomycin non-susceptible enterococci.
AB  - Daptomycin non-susceptible Enterococcus (DNSE) is an emerging clinical problem.
      Little is known about how de novo DNSE infections develop or the risk factors
      associated with them. Determining risk factors associated with de novo DNSE
      infections will aid in understanding the mechanisms of daptomycin non
      susceptibility. Humans in contact with animals worldwide are at risk of carriage
      of multidrug-resistant bacteria. Herein, I review the scientific evidence that
      supports the hypothesis that transport of daptomycin non-susceptibility genes
      between animals and humans may be a possible mechanism for development of de novo
      daptomycin non-susceptibility in enterococci. 

PMID- 24274812
TI  - What can nano do?

PMID- 24274815
TI  - Synthesis, evaluation and pharmacological applications of antioxidants- part 2.

PMID- 24274814
TI  - Nanoparticles for combination drug therapy.
AB  - Nanoparticles have recently emerged as a promising class of carriers for the co
      delivery of multiple drugs. Combination therapies of small-molecule drugs are
      common in clinical practice, and it is anticipated that packaging into single
      macromolecular carriers will enable drug release in precisely balanced ratios and
      rates and in selectively targeted tissues and cells. This vast level of
      pharmacological control is intriguing, especially from the perspective of
      tailoring personalized treatments with maximized therapeutic synergy for
      individual patients. Here, we discuss promising formulations and opportunities to
      employ advanced screening tools and new animal models of disease that can improve
      chances for successful clinical translation. 

PMID- 24274816
TI  - Counteracting oxidative stress in pregnancy through modulation of maternal
      micronutrients and omega-3 fatty acids.
AB  - During pregnancy, oxidative stress has been implicated in the pathophysiology of
      preeclampsia and preterm birth leading to poor birth outcome.
      Hyperhomocysteinemia caused as a consequence of altered micronutrients like folic
      acid and vitamin B12 is associated with increased production of reactive oxygen
      species that generate oxidative stress. These micronutrients are important
      determinants of methyl donor, s-adenosyl methionine while phospholipids are
      important methyl acceptors in the one-carbon metabolic cycle. A series of our
      studies in women during pregnancy have demonstrated altered levels of these
      micronutrients and the negative association of docosahexaenoic acid with
      homocysteine. Various strategies to counteract oxidative stress during pregnancy
      such as antioxidant therapy have been examined and found to be inconsistent. In
      this review, we focus on the role of oxidative stress in pregnancy and discuss
      the possibility of ameliorating it through modulation of maternal micronutrients
      and omega 3 fatty acids especially docosahexaenoic acid. We propose for the first
      time that manipulation of one-carbon metabolism by maternal diet could be a
      potential mechanism to counteract oxidative stress through homocysteine lowering
      effects and help in reducing the risk for adverse pregnancy outcomes. 

PMID- 24274817
TI  - Bio-antioxidants - a chemical base of their antioxidant activity and beneficial
      effect on human health.
AB  - The paradox of aerobic life is that higher eukaryotic organisms cannot exist
      without oxygen, yet oxygen is inherently dangerous to their existence.
      Autoxidation of organic substances frequently occurs via free radical mechanism
      which generates different active radicals and peroxides OH(*), O2 (*-), LO2 (*),
      HOOH, LOOH, so called reactive oxygen species (ROS), which appear to be
      responsible for oxygen toxicity. To survive in such an unfriendly oxygen
      environment, living organisms generate - or obtain from food - a variety of water
      and lipid-soluble antioxidant compounds. Biologically active compounds with
      antioxidant potential, i.e. bio-antioxidants (natural and their synthetic
      analogues) have a wide range of applications. They are important drugs,
      antibiotics, agrochemical substitutes, and food preservatives. Many of the drugs
      today are synthetic modifications of naturally obtained substances. This review
      presents information about the chemical base of antioxidant activities and
      beneficial effects on human health of known and new bio-antioxidants. There is
      abundant literature on the phenolic antioxidants and tocopherols in particular.
      In this review the following bio-antioxidants are considered: A) Carotenoids, B)
      Cathecholamines, C) Phospholipids, D) Chalcones, E) Coumarins, F) Phenolic acids,
      G) Flavonoids, H) Lignans, and I) Tannins. 

PMID- 24274818
TI  - Impact of donor-acceptor functionalization on the properties of linearly pi
      conjugated oligomers: establishing quantitative relationships for the substituent
      and substituent cooperative effect based on quantum chemical calculations.
AB  - To understand better the impact of donor-acceptor substitution on the properties
      of linearly pi-conjugated compounds, we performed a computational study on a
      series of variably substituted trans-polyacetylenes, polyynes, and
      polythiophenes. The focus of this work is on how rapidly the impact of a given
      substituent or a given combination of substituents vanishes along the pi
      conjugated chain. The response of the structural (bond-length alternation,
      rotational barrier) and molecular properties ((hyper)polarizability, chemical
      shift) to substitution is analyzed using different protocols, including a
      superposition model for the evaluation of the cooperative effect of substituents
      in homo- and heterosubstituted oligomers. With the exception of the
      (hyper)polarizability, the impact of donor-acceptor substitution is found to
      vanish following an exponential. The rate of decay of the substituent impact is
      found to be characteristic for each backbone, whereas the choice of substituent
      determines the absolute value of the respective property. The combination of
      substituents is shown to determine whether the substituent cooperative effect on
      a property is of an enhancing or damping nature. The rate of decay of the
      cooperative effect on most properties, including the (hyper)polarizability, is
      also found to follow an exponential law. 

PMID- 24274819
TI  - Challenges in quantifying the patient-reported burden of herpes zoster and post
      herpetic neuralgia in the UK: learnings from the Zoster Quality of Life (ZQOL)
      study.
AB  - BACKGROUND: Acute presentation of herpes zoster (HZ) and the subsequent
      development of post-herpetic neuralgia (PHN) can have a significant impact on
      patients' lives. To date, evidence regarding the human and economic burden of HZ
      and PHN in the UK is limited. To address this knowledge gap a national,
      multicentre, large-scale real-world study was conducted to inform the scientific
      community and healthcare decision-makers. This paper outlines difficulties
      encountered and challenges to conducting real-world studies in the UK, methods
      used to overcome these hurdles and strategies that can be employed to promote and
      facilitate the conduct of future studies. FINDINGS: The Zoster Quality of Life
      (ZQOL) study is the first UK-wide and largest observational study investigating
      patient burden associated with HZ and PHN. A total of 383 patients (229 HZ; 154
      PHN) over the age of 50 years were recruited from 42 primary and
      secondary/tertiary care centres. Patient-reported outcome (PRO) assessments of
      pain, quality of life and treatment satisfaction were completed by all
      participants and supplemented by clinical information from participating
      physicians.Key challenges encountered during the conduct of this study can be
      broadly categorised as follows: 1) identification of centres willing/able to
      participate in the study: lack of resources and limited research experience were
      major barriers to recruitment of centres for participation in the study; 2)
      obtaining local research & development (R&D) approval: lack of clearly defined
      processes and requirements specific to real-world studies and limited degree of
      standardisation between R&D departments in approval procedures led to significant
      variability in submission requirements and lead times for obtaining approval; 3)
      recruitment of study participants: rates of recruitment were slower than
      anticipated, meaning it was necessary to extend the study recruitment period and
      increase the number of participating centres. DISCUSSION: Initiatives designed to
      promote and facilitate the conduct of research in the UK are important for real
      world studies. The ZQOL study shows that opportunities exist for real-word
      research. However, streamlining the R&D approval process where possible and
      further incentivising the participation of primary care centres in such studies
      would help to further facilitate the generation of real-world evidence to inform
      healthcare decisions.

PMID- 24274820
TI  - Right time, right place: improving access to health service through effective
      retention and distribution of health workers.
AB  - This editorial introduces the 'Right time, Right place: improving access to
      health service through effective retention and distribution of health workers'
      thematic series. This series draws from studies in a range of countries and
      provides new insights into what can be done to improve access to health through
      more effective human resources policies, planning and management. The primary
      focus is on health workforce distribution and retention. 

PMID- 24274822
TI  - Self-aligned formation of sub 1 nm gaps utilizing electromigration during metal
      deposition.
AB  - We developed a procedure for the fabrication of sub 1 nm gap Au electrodes via
      electromigration. Self-aligned nanogap formation was achieved by applying a bias
      voltage, which causes electromigration during metal evaporation. We also
      demonstrated the application of this method for the formation of nanogaps as
      small as 1 nm in width, and we found that the gap size can be controlled by
      changing the magnitude of the applied voltage. On the basis of the electric
      conductance and surface-enhanced Raman scattering (SERS) measurements, the
      fabricated gap size was estimated to be nearly equal to the molecular length of
      1,4-benzenedithiol (BDT). Compared with existing electromigration methods, the
      new method provides two advantages: the process currents are clearly suppressed
      and parallel or large area production is possible. This simple method for the
      fabrication of a sub 1 nm gap electrode is useful for single-molecule-sized
      electronics and opens the door to future research on integrated sub 1 nm sized
      nanogap devices. 

PMID- 24274821
TI  - St Gallen molecular subtypes in primary breast cancer and matched lymph node
      metastases--aspects on distribution and prognosis for patients with luminal A
      tumours: results from a prospective randomised trial.
AB  - BACKGROUND: The St Gallen surrogate molecular subtype definitions classify the
      oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes
      according to proliferation rate and/or expression of human epidermal growth
      factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness.
      Primary tumours and lymph node metastases might represent different malignant
      clones, but in the clinical setting only the biomarker profile of the primary
      tumour is used for selection of adjuvant systemic treatment. The present study
      aimed to classify primary breast tumours and matched lymph node metastases into
      luminal A, luminal B, HER2-positive and triple-negative subtypes and compare the
      distributions. METHODS: Eighty-five patients with available tumour tissue from
      both locations were classified. The distribution of molecular subtypes in primary
      tumours and corresponding lymph node metastases were compared, and related to 5
      year distant disease-free survival (DDFS). RESULTS: The St Gallen molecular
      subtypes were discordant between primary tumours and matched lymph node
      metastases in 11% of the patients (p = 0.06). The luminal A subtype in the
      primary tumour shifted to a subtype with a worse prognostic profile in the lymph
      node metastases in 7 of 45 cases (16%) whereas no shift in the opposite direction
      was observed (0/38) (p = 0.02). All subtypes had an increased hazard for
      developing distant metastasis during the first 5 years after diagnosis in both
      primary breast tumours and matched lymph node metastases, compared with the
      luminal A subtype. CONCLUSION: The classification according to the St Gallen
      molecular subtypes in primary tumours and matched lymph node metastases,
      implicates a shift to a more aggressive subtype in synchronous lymph node
      metastases compared to the primary breast tumour. The selection of systemic
      adjuvant therapy might benefit from taking the molecular subtypes in the
      metastatic node into account.

PMID- 24274823
TI  - Distinct lineage of vesiculovirus from big brown bats, United States.
AB  - We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem
      tissue samples from 120 rabies-negative big brown bats with a history of human
      contact. Five percent of the tested bats were infected with this virus. The
      extent of zoonotic exposure and possible health effects in humans from this virus
      are unknown. 

PMID- 24274824
TI  - Investigation of the effect of sugar stereochemistry on biologically relevant
      lyotropic phases from branched-chain synthetic glycolipids by small-angle X-ray
      scattering.
AB  - Synthetic branched-chain glycolipids are suitable as model systems in
      understanding biological cell membranes, particularly because certain natural
      lipids possess chain branching. Herein, four branched-chain glycopyranosides,
      namely, 2-hexyl-decyl-alpha-D-glucopyranoside (alpha-Glc-OC10C6), 2-hexyl-decyl
      beta-D-glucopyranoside (beta-Glc-OC10C6), 2-hexyl-decyl-alpha-D-galactopyranoside
      (alpha-Gal-OC10C6), and 2-hexyl-decyl-beta-D-galactopyranoside (beta-Gal-OC10C6),
      with a total alkyl chain length of 16 carbon atoms have been synthesized, and
      their phase behavior has been studied. The partial binary phase diagrams of these
      nonionic surfactants in water were investigated by optical polarizing microscopy
      (OPM) and small-angle X-ray scattering (SAXS). The introduction of chain
      branching in the hydrocarbon chain region is shown to result in the formation of
      inverse structures such as inverse hexagonal and inverse bicontinuous cubic
      phases. A comparison of the four compounds showed that they exhibited different
      polymorphism, especially in the thermotropic state, as a result of contributions
      from anomeric and epimeric effects according to their stereochemistry. The neat
      alpha-Glc-OC10C6 compound exhibited a lamellar (Lalpha) phase whereas dry alpha
      Gal-OC10C6 formed an inverse bicontinuous cubic Ia3d (QII(G)) phase. Both beta
      anomers of glucoside and galactoside adopted the inverse hexagonal phase (HII) in
      the dry state. Generally, in the presence of water, all four glycolipids formed
      inverse bicontinuous cubic Ia3d (QII(G)) and Pn3m (QII(D)) phases over wide
      temperature and concentration ranges. The formation of inverse nonlamellar phases
      by these Guerbet branched-chain glycosides confirms their potential as materials
      for novel biotechnological applications such as drug delivery and crystallization
      of membrane proteins.

PMID- 24274825
TI  - Familial papular epidermal nevus with "skyline" basal cell layer.
AB  - Papular epidermal nevus with "skyline" basal cell layer (PENS), a novel
      keratinocytic nevus, has recently been described as a mosaic condition with
      varying presentations. We herein describe typical PENS lesions, which usually
      occur sporadically, affecting two members of the same family. The concept of
      paradominant inheritance is proposed to explain the paradox of occasional
      transmission of normally sporadically occurring traits. 

PMID- 24274826
TI  - Vesico-ureteric reflux (VUR) management and screening patterns: are paediatric
      urologists following the 2010 American Urological Association (AUA) guidelines?
AB  - OBJECTIVE: To evaluate the current practice patterns of vesico-ureteric reflux
      (VUR) management and screening among paediatric urologists and their relationship
      with the current American Urological Association (AUA) guidelines in managing and
      treating VUR. SUBJECTS AND METHODS: A 17-question survey was sent out to 476
      paediatric urologists who are members of the Society for Pediatric Urology (SPU).
      In all, 133 respondents answered the survey and results were included for all
      questions. RESULTS: Paediatric urologists who were surveyed were consistent with
      the 2010 AUA guidelines in the initial evaluation of children with VUR,
      continuous antibiotic prophylaxis for the child aged < or >1 year, and follow-up
      evaluation in children with VUR. Most paediatric urologists do not obtain a serum
      creatinine on initial screening of children with VUR. The new guidelines address
      screening of siblings of patients with VUR and most paediatric urologists were
      consistent with these recommendations. Almost one third of responders screened
      all neonates diagnosed with prenatal hydronephrosis regardless of clinical
      history or findings on imaging despite the recommendations of the new guidelines.
      CONCLUSION: We conclude that based on our present sample, most paediatric
      urologists follow the 2010 AUA guidelines on VUR management.

PMID- 24274827
TI  - Workplace safety and health programs, practices, and conditions in auto collision
      repair businesses.
AB  - This article describes the results of a pre-intervention safety assessment
      conducted in 49 auto collision repair businesses and owners' commitments to
      specific improvements. A 92-item standardized audit tool employed interviews,
      record reviews, and observations to assess safety and health programs, training,
      and workplace conditions. Owners were asked to improve at least one-third of
      incorrect, deficient, or missing (not in compliance with regulations or not
      meeting best practice) items, of which a majority were critical or highly
      important for ensuring workplace safety. Two-thirds of all items were present,
      with the highest fraction related to electrical safety, machine safety, and
      lockout/tagout. One-half of shops did not have written safety programs and had
      not conducted recent training. Many had deficiencies in respiratory protection
      programs and practices. Thirteen businesses with a current or past relationship
      with a safety consultant had a significantly higher fraction of correct items, in
      particular related to safety programs, up-to-date training, paint booth and
      mixing room conditions, electrical safety, and respiratory protection. Owners
      selected an average of 58% of recommended improvements; they were most likely to
      select items related to employee Right-to-Know training, emergency exits, fire
      extinguishers, and respiratory protection. They were least likely to say they
      would improve written safety programs, stop routine spraying outside the booth,
      or provide adequate fire protection for spray areas outside the booth. These
      baseline results suggest that it may be possible to bring about workplace
      improvements using targeted assistance from occupational health and safety
      professionals. 

PMID- 24274828
TI  - Does self-monitoring by means of symptom diaries improve asthma control in
      children?
AB  - OBJECTIVE: Keeping symptom diaries on a regular basis may facilitate the
      execution of symptom-based action plans, enhance the patients' adherence to
      treatment program and finally allow better asthma control. We hypothesize that
      disease control in children who keep symptom diaries regularly would be better
      compared to children who do not keep symptom diaries regularly. METHODS:
      Asthmatic children, aged between 6 and 17 years, who were monitored at least 2
      years at our outpatient clinic and examined at least twice within the last year,
      were enrolled in this study. The patients were assigned to the following two
      groups: group I included the patients who keep symptom diaries regularly and
      group II included the patients who do not keep symptom diaries regularly. Asthma
      control parameters of patients during the last year were investigated. The number
      of asthma attacks require systemic corticosteroid use, the frequency of emergency
      department (ED) admissions and the number of attacks requiring hospitalization,
      forced expiratory volume in 1 s (FEV1) values and asthma control test (ACT)
      scores were compared. RESULTS: 89 (26.2%) of 340 patients included in the study
      were identified to keep a symptom diary regularly. Although age (p = 0.20) and
      sex (p = 0.48) did not differ significantly between the groups, regular use of
      anti-inflammatory drug was found to be significantly higher in group I (p <
      0.001). When all of the study parameters were compared using a multivariate
      analysis, the number of systemic corticosteroid use, ED visits, attacks requiring
      hospitalization and ACT scores and FEV1 did not differ significantly between the
      groups (p > 0.05 in all of the parameters). CONCLUSIONS: Keeping a symptom diary
      on a regular basis in asthmatic children was shown to have neither beneficial
      effect on the day-to-day asthma control nor a decrease in the future risk of
      asthma control.

PMID- 24274829
TI  - The delivery of heavy menstrual bleeding services in England and Wales after
      publication of national guidelines: a survey of hospitals.
AB  - BACKGROUND: In 2007-2008, two UK-based organisations, the National Institute for
      Health and Clinical Excellence and the Royal College of Obstetricians and
      Gynaecologists, published guidelines for the management of care and organisation
      of outpatient services for women with heavy menstrual bleeding (HMB). In 2010,
      this study was conducted to provide an update on guideline-related services
      provided in England and Wales, and whether they are consistent with national
      clinical guidelines two to three years after publication. METHODS: An
      organisational survey of outpatient gynaecology clinics was conducted of 221
      hospitals in 154 acute National Health Service (NHS) trusts in England and Wales.
      A questionnaire was distributed to all hospitals to examine provision of
      diagnostic and therapeutic services in outpatient settings. Descriptive
      statistics were used to summarize results. RESULTS: The response rate was 100%.
      For diagnosis, 80% of hospitals had ultrasound, 87% had hysteroscopy, and 98% had
      endometrial biopsy available. Overall, 76% of hospitals provided an information
      leaflet, 8% referred patients to a website for information, and 20% did not
      provide any written information. A dedicated menstrual bleeding clinic was
      present in 38% of hospitals. Only 30% of hospitals reported that they have a
      local written protocol regarding the care and management of women with HMB.
      CONCLUSION: The majority of hospitals offer appropriate diagnostic and surgical
      services for women with HMB. However, local protocol development may not reflect
      the local services. It may be that hospitals are finding it difficult to summon
      resources to provide clinics for women with menstrual disorders.

PMID- 24274830
TI  - Cochlear implant after bacterial meningitis.
AB  - BACKGROUND: The aim of this retrospective case study at a tertiary referral
      center was to investigate the outcome of cochlear implantation (CI) in children
      with sensorineural hearing loss due to meningitis compared to CI in children with
      deafness due to other reasons. METHODS: This post-meningial group (PMG) consisted
      of 22 children undergoing CI due to deafness induced by meningitis, between
      December 1996 and January 2012. Five children had bilateral simultaneous
      implantation. None was excluded and the children were followed for at least 3
      years. Operations were carried out by one of two surgeons using similar
      techniques in all cases. Each patient from the PMG was matched 2:1 with children
      having implantation for other reasons according to age and follow up (control
      group). RESULTS: Overall, the median category of auditory performance (CAP) and
      speech intelligibility rating (SIR) score were not statistically significantly
      different between the two groups. The presence of additional central nervous
      system (CNS) disorders (post-meningeal sequelae), however, correlated
      significantly with poorer outcome CONCLUSIONS: CI was a safe procedure without
      surgical complications in the present study. It is possible to restore auditory
      capacity and speech performance to a degree comparable to children undergoing
      implantation for other reasons. A statistically important variable is secondary
      CNS involvement. The rehabilitation program after CI should be adjusted according
      to these additional handicaps. It is recommended to screen meningitis patients as
      fast as possible to identify those with hearing loss and initiate treatment with
      hearing aids or CI.

PMID- 24274831
TI  - Phosphonium chloromercurate room temperature ionic liquids of variable
      composition.
AB  - The system trihexyl(tetradecyl)phosphonium ([P66614]Cl)/mercury chloride (HgCl2)
      has been investigated by varying the stoichiometric ratios from 4:1 to 1:2 (25,
      50, 75, 100, 150, and 200 mol % HgCl2). All investigated compositions turn out to
      give rise to ionic liquids (ILs) at room temperature. The prepared ionic liquids
      offer the possibility to study the structurally and compositionally versatile
      chloromercurates in a liquid state at low temperatures in the absence of
      solvents. [P66614]2[HgCl4] is a simple IL with one discrete type of anion, while
      [P66614]{HgCl3} (with {} indicating a polynuclear arrangement) is an ionic liquid
      with a variety of polyanionic species, with [Hg2Cl6](2-) apparently being the
      predominant building block. [P66614]2[Hg3Cl8] and [P66614][Hg2Cl5] appear to be
      ILs at ambient conditions but lose HgCl2 when heated in a vacuum. For the liquids
      with the compositions 4:1 and 4:3, more than two discrete ions can be evidenced,
      namely, [P66614](+), [HgCl4](2-), and Cl(-) and [P66614](+), [HgCl4](2-), and the
      polynuclear {HgCl3}(-), respectively. The different stoichiometric compositions
      were characterized by (199)Hg NMR, Raman- and UV-vis spectroscopy, and cyclic
      voltammetry, among other techniques, and their densities and viscosities were
      determined. The [P66614]Cl/HgCl2 system shows similarities to the well-known
      chloroaluminate ILs (e.g., decrease in viscosity with increasing metal content
      after addition of more than 0.5 mol of HgCl2/mol [P66614]Cl, increasing density
      with increasing metal content, and the likely formation of
      polynuclear/polymeric/polyanionic species) but offer the advantage that they are
      air and water stable. 

PMID- 24274832
TI  - Porcine epidemic diarrhea virus variants with high pathogenicity, China.

PMID- 24274833
TI  - Safe transfer technique.

PMID- 24274834
TI  - Isolation and identification of new phytoconstituents from the fruit extract of
      Amomum subulatum Roxb.
AB  - The fruits of Amomum subulatum Roxb. (Zingiberaceae) (large cardamom), cultivated
      in the northern Himalayas, are used to treat stomach disorders, pulmonary
      diseases and liver complaints. Phytochemical investigation of the fruits led to
      the isolation of four new chemical compounds characterised as geranil-3(10)-en-9
      olyl octadec-9-enoate, geranil-3(10)-en-9-carboxyl-beta-D-arabinopyranoside,
      geranilan-9-carboxy-alpha-L-arabinopyranoside and stigmast-5-en-3beta-ol-3beta-D
      arabinopyranosyl-2'-(3"-methoxy) benzoate-3'-octadec-9''',12''',15'''-trienoate,
      along with the known compounds oleodilinolein and glyceryl trilinoleniate on the
      basis of spectral data analysis.

PMID- 24274835
TI  - Acute hepatitis B in blood donors over a 5-year period in England and North
      Wales: who is getting infected?
AB  - BACKGROUND: Hepatitis B virus (HBV) remains the infection most frequently
      recognized by donation testing in blood donors. It is usually a persistent
      infection and mostly reflects the country of origin of the donor or the donor's
      family. There are, however, a minority of acute infections and this study
      undertook their phylogenetic analysis to determine the likely source of
      infection. STUDY DESIGN AND METHODS: Plasma samples from 11 donors donating
      between July 2005 and June 2010, whose test results revealed recent infection
      with hepatitis B, were available for further analysis. Plasma DNA was extracted,
      amplified, sequenced, and analyzed phylogenetically. Donor and virus
      characteristics were compared with the overall demography of all hepatitis B
      infected donors attending over the same period. RESULTS: Three of the 11
      individuals were first-time donors. Nine were male, of whom eight were white
      British. All had serum markers of very recent infection. Only two indicated known
      HBV exclusion risk factors at postdonation discussion not declared previously.
      Genotype A was present in seven, Genotype B in two, and Genotype C in two,
      contrasting with the pattern in persistently infected persons in the United
      Kingdom. A single A2 strain was identified in six of the white British male
      donors, suggesting epidemiologic linkage. CONCLUSION: Phylogenetic analysis of
      HBV-infected donors performed in real time can potentially lead to identification
      of undeclared risk factors that donor health questionnaires may fail to identify.

PMID- 24274836
TI  - eLearning course may shorten the duration of mechanical restraint among
      psychiatric inpatients: a cluster-randomized trial.
AB  - BACKGROUND: The management of psychiatric inpatients exhibiting severely
      disturbed and aggressive behaviour is an important educational topic. Well
      structured, IT-based educational programmes (eLearning) often ensure quality and
      may make training more affordable and accessible. AIMS: The aim of this study was
      to explore the impact of an eLearning course for personnel on the rates and
      duration of seclusion and mechanical restraint among psychiatric inpatients.
      METHODS: In a cluster-randomized intervention trial, the nursing personnel on 10
      wards were randomly assigned to eLearning (intervention) or training-as-usual
      (control) groups. The eLearning course comprised six modules with specific topics
      (legal and ethical issues, behaviour-related factors, therapeutic relationship
      and self-awareness, teamwork and integrating knowledge with practice) and
      specific learning methods. The rates (incidents per 1000 occupied bed days) and
      durations of the coercion incidents were examined before and after the course.
      RESULTS: A total of 1283 coercion incidents (1143 seclusions [89%] and 140
      incidents involving the use of mechanical restraints [11%]) were recorded on the
      study wards during the data collection period. On the intervention wards, there
      were no statistically significant changes in the rates of seclusion and
      mechanical restraint. However, the duration of incidents involving mechanical
      restraints shortened from 36.0 to 4.0 h (median) (P < 0.001). No statistically
      significant changes occurred on the control wards. CONCLUSIONS: After our
      eLearning course, the duration of incidents involving the use of mechanical
      restraints decreased. However, more studies are needed to ensure that the content
      of the course focuses on the most important factors associated with the seclusion
      related elements. The eLearning course deserves further development and further
      studies. The duration of coercion incidents merits attention in future research.

PMID- 24274837
TI  - Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in
      Sweden.
AB  - AIMS: To determine the cost-effectiveness of long-acting injectable (LAI)
      antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision
      tree was developed for Sweden using published data and expert opinion. Five
      treatment strategies lasting 1 year were compared: paliperidone palmitate (PP
      LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate
      (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs
      switched to another depot; subsequent failures received clozapine. Resources and
      employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK),
      from standard government lists. The model calculated the average cost/patient and
      quality-adjusted life-years (QALYs), which were combined into incremental cost
      effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model
      stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient
      (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI
      followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI
      cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK
      (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The
      greatest proportions of costs (52.5-83.8%) were for institutional care; indirect
      costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and
      hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated
      OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI
      in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI
      in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000
      iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden
      for chronic schizophrenia and cost-saving overall to the healthcare system.

PMID- 24274838
TI  - A register-based study of long-term healthcare use before and after
      psychotherapy.
AB  - BACKGROUND: Psychotherapeutic treatment for non-psychotic disorders is associated
      with significant reduction in patients' symptoms, and therefore it is believed
      that treatment improves health and decreases the need for additional healthcare.
      However, little is known about long-term changes in utilization of healthcare
      services. AIM: To investigate long-term changes in utilization of public
      healthcare services for patients referred to psychotherapeutic treatment.
      METHODS: A pre-post study with 761 consecutive patients and 15,220 matched
      individuals in a matched population reference group. Data from a comprehensive
      set of healthcare services were collected from central registries for 4 years
      prior to intake and for 4 years after completion of treatment. RESULTS: Of the
      761 patients, 216 did not show up for treatment and 545 completed treatment.
      Completer patients achieved a substantial reduction in symptoms (effect size, ES
      = 0.99). However, completer patients increased their use of all healthcare
      services by 296% (ES = 0.58) in the 4th year pre-post comparison, while the
      reference group increased usage by 99% (ES = 0.23). Completer patients had
      significantly higher increase in contacts with psychiatric hospitals (P < 0.008),
      contacts with primary care psychologists (P < 0.001), psychotropic medication (P
      < 0.001) and contacts with primary care physicians (P < 0.001) than the reference
      group at the 4th year pre-post comparison. CONCLUSION: Over a long-term period,
      patients who completed psychotherapeutic treatment increased utilization of
      healthcare services. Studies are needed to clarify how and why psychotherapeutic
      treatment does not necessarily lead to a reduction in the utilization of
      healthcare services for the average patient and to evaluate other potential
      interventions for patients with mental problems and include efficiency studies in
      this evaluation.

PMID- 24274839
TI  - Association between body mass index and mental health among Scottish adult
      population: a cross-sectional study of 37,272 participants.
AB  - BACKGROUND: The evidence is conflicting as to whether body mass index (BMI) is
      associated with mental health and, if so, to what extent it varies by sex and
      age. We studied mental health across the full spectrum of BMI among the general
      population, and conducted subgroup analyses by sex and age. METHOD: We undertook
      a cross-sectional study of a representative sample of the Scottish adult
      population. The Scottish Health Survey provided data on mental health, measured
      by the General Health Questionnaire-12 (GHQ), BMI, demographic and life-style
      information. Good mental health was defined as a GHQ score <4, and poor mental
      health as a GHQ score ?4. Logistic regression models were applied. RESULTS: Of
      the 37 272 participants, 5739 (15.4%) had poor mental health. Overall, overweight
      participants had better mental health than the normal-weight group [adjusted odds
      ratio (OR) 0.93, 95% confidence interval (CI) 0.87-0.99, p = 0.049], and
      individuals who were underweight, class II or class III obese had poorer mental
      health (class III obese group: adjusted OR 1.26, 95% CI 1.05-1.51, p = 0.013).
      There were significant interactions of BMI with sex (p = 0.013) and with age (p <
      0.001). Being overweight was associated with significantly better mental health
      in middle-aged men only. In contrast, being underweight at all ages or obese at a
      young age was associated with significantly poorer mental health in women only.
      CONCLUSIONS: The adverse associations between adiposity and mental health are
      specific to women. Underweight women and young women who are obese have poorer
      mental health. In contrast, middle-aged overweight men have better mental health.

PMID- 24274840
TI  - Influence of particle coating and matrix constituents on the cloud point
      extraction efficiency of silver nanoparticles (Ag-NPs) and application for
      monitoring the formation of Ag-NPs from Ag(+).
AB  - For the quantification of silver nanoparticles (Ag-NPs) in environmental samples
      using cloud point extraction (CPE) for selective enrichment, surface modification
      of the Ag-NPs and matrix effects can play a key role. In this work we validate
      CPE with respect to the influence of different coatings and naturally occurring
      matrix components. The Ag-NPs tested were functionalized with inorganic and
      organic compounds as well as with biomolecules. Commercially available NPs and
      NPs synthesized according to methods published in the literature were used. We
      found that CPE can extract almost all Ag-NPs tested with very good efficiencies
      (82-105%). Only Ag-NPs functionalized with BSA (bovine serum albumin), which is a
      protein with the function to keep colloids in solution, cannot be extracted. No
      or little effect of environmentally relevant salts, organic matter, and inorganic
      colloids on the CPE of AgNPs was found. Additionally we used CPE to observe the
      in situ formation of Ag-NPs produced by the reduction of Ag(+) with natural
      organic matter (NOM). 

PMID- 24274841
TI  - Nonoperative treatment of unicompartmental arthritis: from bracing to injection.
AB  - The published recommendations for the nonoperative treatment of osteoarthritis
      (OA) of the knee include weight loss, physical therapy to strengthen lower
      extremity musculature, nonsteroidal antiinflammatories, nutritional supplements,
      topical treatments, and steroid injections. Evidenced-based results have been
      mixed using these treatment modalities. The results using unloader braces and
      viscosupplementation have also been variable. This article reviews the use of
      conservative treatment of OA of the knee. 

PMID- 24274842
TI  - Diagnosis and indications for treatment of unicompartmental arthritis.
AB  - Unicompartmental knee arthroplasty (UKA) is a reliable operation for isolated
      unicompartmental arthritis. A comprehensive understanding of the limitations of
      UKA is crucial for success in the young patient. Obesity may impact implant
      longevity; however, acceptable results can be achieved with precise component
      implantation and careful patient selection. UKA for degenerative medial
      compartment arthritis with attritional anterior cruciate ligament (ACL) rupture
      is generally contraindicated. However, concomitant ACL/UKA reconstruction is a
      dependable treatment for early posterior-medial compartment arthritis caused by
      an acute ACL rupture. Regardless of its limitations, the functional benefits and
      limited morbidity of UKA make it an appealing treatment option for
      unicompartmental disease. 

PMID- 24274843
TI  - Arthroscopic debridement of unicompartmental arthritis: fact or fiction?
AB  - Patients with recurrent or mechanical symptoms of unicompartmental knee arthritis
      that have failed conservative management are candidates for surgical
      intervention. Surgical options include debridement, lavage, chondroplasty, bone
      marrow-stimulating techniques, chondrocyte transfer, and chondrocyte
      implantation. These techniques have been well studied but it is still unclear
      which technique is superior. Various factors need to be accounted for when
      choosing the proper technique; among the factors discussed are the patient's age
      and the size of the articular cartilage defect. 

PMID- 24274844
TI  - The anterior cruciate ligament-deficient knee and unicompartmental arthritis.
AB  - Treatment of medial and lateral compartment arthritis in the anterior cruciate
      ligament (ACL)-deficient knee remains a topic of debate among orthopedic
      surgeons. This article discusses the treatment options for the ACL-deficient knee
      with unicompartmental arthritis and provides a rationale for clinical decision
      making in this difficult group of patients. Unicondylar knee arthroplasty (UKA)
      is a viable option in a select group of patients to decrease pain and maintain an
      active lifestyle. When performing a UKA in an ACL-deficient knee, it is important
      to manage appropriate expectations for a successful outcome. 

PMID- 24274845
TI  - UniCAP as an alternative for unicompartmental arthritis.
AB  - Medial tibiofemoral arthrosis is a disabling disease, particularly for active
      middle-aged patients who have failed conservative and biological precursor
      treatments. The UniCAP Bipolar Knee Resurfacing System (Arthrosurface,
      Incorporated, Franklin, Massachusetts) was introduced in 2008 to add a new layer
      to reconstructive joint surgery, allowing for a delay in traditional joint
      replacement procedures. It utilizes intraoperative, 3-dimensional joint surface
      mapping to fit and implant defect-sized components that are matched to the
      individual joint surface. 

PMID- 24274846
TI  - Unicondylar knee: the Arthrex experience.
AB  - Unicondylar arthroplasty of the knee in appropriate patients has the ability to
      relieve pain and restore function. The procedure allows for the preservation of
      more normal kinematics and function compared with total knee arthroplasty. Using
      a gap balancing technique allows the surgeon to customize placement of the
      prosthesis to optimize range of motion and maintain ligament isometry and
      stability throughout range of motion. 

PMID- 24274847
TI  - The simple unicondylar knee: extramedullary technique.
AB  - Unicompartmental knee arthroplasty (UKA) is a successful procedure that is
      gaining popularity in the United States. Outcomes of UKA depend on careful
      patient selection as well a meticulous surgical technique and avoiding
      overcorrection of the preoperative deformity. Intramedullary and extramedullary
      (EM) cutting guides are available for most commercial systems. EM techniques
      avoid cannulating the medullary canals of the femur or tibia, thus diminishing
      the chances of marrow emboli and bleeding from the canal during the procedure.
      Both with accurate cuts high levels of success with precise component alignment
      can be achieved when using EM techniques for UKA. 

PMID- 24274848
TI  - Unicondylar knee arthroplasty: intramedullary technique.
AB  - Unicondylar knee arthroplasty (UKA) is a challenging surgical procedure for many
      orthopedic surgeons when compared with total knee arthroplasty (TKA). Given the
      proven similarities in knee biomechanics between UKA and the native knee and
      recent evidence showing excellent survivorship and functionality, UKA is an
      excellent alternative to TKA in the appropriate patient. This article discusses
      the use of intramedullary guides for preparation in partial knee replacement
      surgery. The concerns of complications arising from cannulating the medullary
      canal and excessive bleeding have not been seen. The intramedullary UKA yields
      high levels of success and long-term outcomes, with excellent alignment. 

PMID- 24274849
TI  - Mobile-bearing unicondylar knee arthroplasty: the Oxford experience.
AB  - With the recent increase in medial unicompartmental arthroplasty, this article
      reviews the design history, indications, results, and modern technique for the
      implantation of the Oxford mobile-bearing unicompartmental arthroplasty. The
      article also discusses how the indications for the Oxford differ from the
      historical indications for medial unicompartmental arthroplasty and supports this
      paradigm shift with review of the recent data. A detailed series of surgical
      pearls is also presented to help surgeons with the surgical nuances of the Oxford
      partial knee. 

PMID- 24274850
TI  - Robotic-assisted unicompartmental knee arthroplasty: the MAKO experience.
AB  - Since its introduction, unicompartmental knee arthroplasty has been controversial
      because of poor early clinical outcomes due to implant design, bony fixation,
      surgical instrumentation, and technique. Improvements in surgical technique and
      implant design have resulted in improved results and greater survivorship. The
      ability to obtain accurate implant placement includes avoiding surgeon decisions
      leading to potential errors. These errors include alignment in the sagittal,
      coronal, and axial planes on each prepared condyle as well as the preservation of
      the joint line and the resulting overall limb alignment as something critical to
      obtaining a successful outcome. 

PMID- 24274851
TI  - Patient-specific instrumentation and return to activities after unicondylar knee
      arthroplasty.
AB  - In the past decade, there has been a major increase in the use of
      unicompartmental knee arthroplasty (UKA) as surgical techniques have been refined
      and patient selection has improved. UKAs now account for 8% to 10% of knee
      arthoplasty procedures. Recent studies have suggested excellent medium- and long
      term results of UKA. Overall, results have shown 85% to 90% survivorship at 10
      years, with 90% of patients reporting good to excellent subjective and objective
      outcomes. Recent studies suggest that unicompartmental arthroplasty allows a high
      percentage of patients to return to presurgical sport and activity participation.

PMID- 24274852
TI  - Outcomes and complications of unicondylar arthroplasty.
AB  - Unicompartmental knee arthroplasty has experienced resurgence in popularity
      because of the lower morbidity of the procedure and the proposed benefits over
      total knee replacement in appropriately selected patients. Improved component
      designs and advanced surgical techniques have promoted excellent results.
      Expanded indications to include the very young and the elderly have yielded
      comparable clinical outcomes. Nonetheless, the success of unicompartmental
      replacement depends on proper surgical technique and patient selection. Distinct
      surgical considerations exist depending on whether the medial, lateral, or
      patellofemoral compartment is replaced. Long-term studies have shown that
      unicompartmental knee replacement is an alternative to total knee arthroplasty. 

PMID- 24274853
TI  - Future trends for unicompartmental arthritis of the knee: injectables & stem
      cells.
AB  - Arthritis is one of the most frequent musculoskeletal problems, causing pain,
      disability, and a significant economic burden. In this article, we discuss
      current nonsurgical injectable treatment options as well as future trends for
      cartilage lesions and early arthritis of the knee. We cover some potential
      treatments for knee osteoarthritis, including stem cell and gene therapies. 

PMID- 24274854
TI  - Unicompartmental knee arthritis.

PMID- 24274855
TI  - Note from consulting editor.

PMID- 24274856
TI  - The increasing recognition of unicompartment arthritis. Preface.

PMID- 24274857
TI  - Development of a multipoint quantitation method to simultaneously measure
      enzymatic and structural components of the Clostridium thermocellum cellulosome
      protein complex.
AB  - Clostridium thermocellum has emerged as a leading bioenergy-relevant microbe due
      to its ability to solubilize cellulose into carbohydrates, mediated by
      multicomponent membrane-attached complexes termed cellulosomes. To probe
      microbial cellulose utilization rates, it is desirable to be able to measure the
      concentrations of saccharolytic enzymes and estimate the total amount of
      cellulosome present on a mass basis. Current cellulase determination
      methodologies involve labor-intensive purification procedures and only allow for
      indirect determination of abundance. We have developed a method using multiple
      reaction monitoring (MRM-MS) to simultaneously quantitate both enzymatic and
      structural components of the cellulosome protein complex in samples ranging in
      complexity from purified cellulosomes to whole cell lysates, as an alternative to
      a previously developed enzyme-linked immunosorbent assay (ELISA) method of
      cellulosome quantitation. The precision of the cellulosome mass concentration in
      technical replicates is better than 5% relative standard deviation for all
      samples, indicating high precision for determination of the mass concentration of
      cellulosome components. 

PMID- 24274858
TI  - Synthetically encoding 10 nm morphology in silicon nanowires.
AB  - Si nanowires (NWs) have been widely explored as a platform for photonic and
      electronic technologies. Here, we report a bottom-up method to break the
      conventional "wire" symmetry and synthetically encode a high-resolution array of
      arbitrary shapes, including nanorods, sinusoids, bowties, tapers, nanogaps, and
      gratings, along the NW growth axis. Rapid modulation of phosphorus doping
      combined with selective wet-chemical etching enabled morphological features as
      small as 10 nm to be patterned over wires more than 50 MUm in length. This
      capability fundamentally expands the set of technologies that can be realized
      with Si NWs, and as proof-of-concept, we demonstrate two distinct applications.
      First, nanogap-encoded NWs were used as templates for Noble metals, yielding
      plasmonic structures with tunable resonances for surface-enhanced Raman imaging.
      Second, core/shell Si/SiO2 nanorods were integrated into electronic devices that
      exhibit resistive switching, enabling nonvolatile memory storage. Moving beyond
      these initial examples, we envision this method will become a generic route to
      encode new functionality in semiconductor NWs. 

PMID- 24274859
TI  - Effects of white, blue, and red light-emitting diodes on carotenoid biosynthetic
      gene expression levels and carotenoid accumulation in sprouts of tartary
      buckwheat (Fagopyrum tataricum Gaertn.).
AB  - In this study, the optimum wavelengths of light required for carotenoid
      biosynthesis were determined by investigating the expression levels of carotenoid
      biosynthetic genes and carotenoid accumulation in sprouts of tartary buckwheat
      (Fagopyrum tataricum Gaertn.) exposed to white, blue, and red light-emitting
      diodes (LEDs). Most carotenoid biosynthetic genes showed higher expression in
      sprouts irradiated with white light at 8 days after sowing than in those
      irradiated with blue and red lights. The dominant carotenoids in tartary
      buckwheat sprouts were lutein and beta-carotene. The richest accumulation of
      total carotenoids was observed in sprouts grown under white light (1282.63 MUg g(
      1) dry weight), which was relatively higher than that in sprouts grown under blue
      and red lights (940.86 and 985.54 MUg g(-1), respectively). This study might
      establish an effective strategy for maximizing the production of carotenoids and
      other important secondary metabolites in tartary buckwheat sprouts by using LED
      technology.

PMID- 24274860
TI  - Autonomic dysfunction in reversible cerebral vasoconstriction syndromes.
AB  - BACKGROUND: Autonomic imbalance may play an important role in the pathogenesis of
      reversible cerebral vasoconstriction syndromes (RCVS). This study aimed to assess
      the autonomic function by analyzing heart rate variability (HRV) in patients with
      RCVS. METHODS: Patients with RCVS and age- and gender-matched controls were
      consecutively recruited. All patients (both ictal and remission stage) and
      controls underwent 24-hour ambulatory electrocardiographic (ECG) recordings. HRV
      measures covering time and frequency domains were used to assess autonomic
      functioning. RESULTS: Thirty-nine patients with RCVS and 39 controls completed
      the study. Compared to the controls, RCVS patients during the ictal stage showed
      reductions in parasympathetic-related indices, including the root mean square of
      difference of consecutive interbeat intervals (RMSSD) (22.1 +/- 7.0 vs. 35.2 +/-
      14.2, p < 0.001), the percentage of adjacent intervals that varied by more than
      50 ms (pNN50) (3.7 +/- 3.4 vs. 10.6 +/- 8.1, p < 0.001), and high-frequency power
      (HF) (5.82 +/- 0.73 vs. 6.77 +/- 0.74; p < 0.001), and increased low
      frequency/high-frequency (LF/HF) ratio (index of sympathovagal balance) (3.38 +/-
      1.32 vs. 2.48 +/- 1.07; p =0.001). These HRV indices improved partially but
      remained significantly different from controls during remission. CONCLUSIONS:
      Decreased parasympathetic modulations and accentuated sympathetic activity might
      be a biological trait in patients with RCVS.

PMID- 24274861
TI  - Obesity and liver disease: the epidemic of the twenty-first century.
AB  - Obesity is a rapidly growing health problem that is associated with more than 65
      comorbidities and results in substantially increased all-cause mortality. The
      increase of obesity has played an important role in the increasing prevalence of
      nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease
      in the United States. Understanding the prevalence, comorbidities, and
      pathogenesis of obesity provides an essential foundation for clinicians who care
      for individuals with NAFLD.

PMID- 24274862
TI  - Obesity-associated nonalcoholic fatty liver disease.
AB  - Obesity is strongly associated with the prevalence of nonalcoholic fatty liver
      disease (NAFLD) in adult and pediatric populations. Nutrition, physical activity,
      and behavioral modifications are critical components of the treatment regimen for
      all obese patients with NAFLD. Bariatric surgeries that affect or restrict the
      flow of food through the gastrointestinal tract may improve liver histology in
      morbidly obese patients with nonalcoholic steatohepatitis (NASH), although
      randomized clinical trials and quasi-randomized clinical studies are lacking.
      Early detection of NASH and hepatic fibrosis using noninvasive biochemical and
      imaging markers that may replace liver biopsy is the current challenge.

PMID- 24274863
TI  - The impact of obesity on liver histology.
AB  - Obesity and insulin resistance produce alterations in the liver's normal role in
      lipid metabolism resulting in a sequence of changes recognizable on liver biopsy.
      Hepatocellular fat vacuoles increase with BMI, producing steatosis.
      Steatohepatitis occurs when there is also cytoskeletal damage with loss of
      keratin filaments, ballooning of affected liver cells and formation of Mallory
      Denk bodies. Activation of hepatic stellate cells produces fibrosis in the
      perisinusoidal spaces. With continuing fibrogenesis there is progression to
      bridging fibrosis and cirrhosis. Hepatocellular carcinoma may develop in the
      cirrhotic liver, but both hepatocellular adenoma and hepatocellular carcinoma may
      occur in pre-cirrhotic fatty liver disease.

PMID- 24274864
TI  - Adipose tissue as an endocrine organ.
AB  - Obesity is one of the most important health challenges faced by developed
      countries and is increasingly affecting adolescents and children. Obesity is also
      a considerable risk factor for the development of numerous other chronic
      diseases, such as insulin resistance, type 2 diabetes, heart disease and
      nonalcoholic fatty liver disease. The epidemic proportions of obesity and its
      numerous comorbidities are bringing into focus the highly complex and
      metabolically active adipose tissue. Adipose tissue is increasingly being
      considered as a functional endocrine organ. This article discusses the endocrine
      effects of adipose tissue during obesity and the systemic impact of this
      signaling.

PMID- 24274865
TI  - Obesity and NAFLD: the role of bacteria and microbiota.
AB  - There are trillions of microorganisms in the human intestine collectively called
      gut microbiota. Obesity may be affected by the gut microbiota through energy
      harvesting and fat storage by the bacteria. Small intestinal bacterial overgrowth
      is also responsible for endotoxemia, systemic inflammation, and its consequences
      including obesity and nonalcoholic fatty liver disease (NAFLD). Relationship
      between gut microbiota and NAFLD is also dependent on altered choline and bile
      acid metabolism and endogenous alcohol production by gut bacteria. Further
      evidence linking gut microbiota with obesity and NAFLD comes from studies showing
      usefulness of probiotics in animals and patients with NAFLD. This article reviews
      the relationship among gut microbiota, obesity, and NAFLD.

PMID- 24274866
TI  - The role of medications for the management of patients with NAFLD.
AB  - The article is intended to provide an overview of the strengths and limits of
      controlled trials of pharmacologic treatment of nonalcoholic fatty liver disease.
      No drug has so far been approved, although validated on histologic outcomes.
      Several new drugs are under scrutiny, acting with different mechanisms along the
      chain of events from fatty liver to fibrosis, cirrhosis, and hepatocellular
      carcinoma. The article investigates which drug, if any, should be preferred for a
      tailored intervention in individual patients, according to age, comorbidities,
      and disease severity, and if treatment should be continued lifelong, to prevent
      disease progression and long-term occurrence of cirrhosis.

PMID- 24274867
TI  - The role of diet and nutritional intervention for the management of patients with
      NAFLD.
AB  - During the last few decades, the prevalence of obesity, insulin resistance and
      non-alcoholic fatty liver disease (NAFLD) have dramatically increased. Nutrition
      and modern lifestyle habits are intimately involved in this epidemiological
      change. Although lifestyle intervention can theoretically revert the metabolic
      disturbances and prevent the long term complications of NAFLD, its efficacy is
      diminished in clinical practice by poor implementation and reduced adherence to
      lifestyle intervention programs. In this article we summarize the main elements
      of dietary interventions for NAFLD, describe practical strategies to optimize
      efficacy and review potential nutritional strategies under development that
      hopefully will improve outcomes in the future.

PMID- 24274868
TI  - Role of exercise in optimizing the functional status of patients with
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is frequently concomitant with obesity.
      This article discusses factors that influence health and functional outcomes of
      people who develop NAFLD, including increased burden of illness, whole body
      function, performance, and perception of self-efficacy. Changes in
      macronutrients, amount of calories consumed, and decreased physical activity all
      negatively influence patient outcome. The benefits of exercise in this population
      are also discussed. To be effective, exercise must be performed, regularly and in
      conjunction with dietary and other behavioral change. Therefore, a lifelong
      commitment to exercise, activity, and diet are needed if NAFLD is to be
      successfully treated. 

PMID- 24274869
TI  - Surgical management of obesity in patients with morbid obesity and nonalcoholic
      fatty liver disease.
AB  - Most patients with severe complex obesity presenting for bariatric-metabolic
      surgery have nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with
      central obesity, insulin resistance, type 2 diabetes, hypertension, and obesity
      related dyslipidemia. Weight loss should be a primary therapy for NAFLD. However,
      evidence supporting intentional weight loss as a therapy for NAFLD is limited.
      Bariatric-metabolic surgery provides the most reliable method of achieving
      substantial sustained weight loss and the most commonly used procedures are
      associated with reduced steatosis and lobular inflammatory changes, but there are
      mixed reports regarding fibrosis. Surgery should complement treatment of obesity
      related comorbidity, but not replace established therapy.

PMID- 24274870
TI  - The impact of obesity and metabolic syndrome on chronic hepatitis C.
AB  - The metabolic syndrome and the hepatitis C virus (HCV) infection are 2 global
      health care challenges with a complex interaction. Insulin resistance, a central
      component of the metabolic syndrome, is epidemiologically and
      pathophysiologically intrinsically linked to HCV infection. Insulin resistance
      and diabetes affect clinical outcomes in patients with liver disease related to
      HCV, namely, incidence of hepatocellular carcinoma, liver-related mortality,
      fibrosis progression rate, response to antiviral therapy, and possibly the
      incidence of cardiovascular events. Viral and metabolic steatosis and its
      interactions with HCV and the metabolic syndrome are discussed. Management and
      the need for further research conclude the article.

PMID- 24274871
TI  - The impact of obesity and metabolic syndrome on alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) remains a major cause of chronic liver diseases and
      liver failure. Population-based prospective studies and patient cohort studies
      have demonstrated that obesity and the metabolic syndrome exacerbate progression
      of ALD and increase hepatocellular carcinoma (HCC) incidence and mortality.
      Emerging evidence also suggests a synergism between alcohol and obesity in
      mortality and HCC incidence. Recognition of these increased risks and detection
      of early-stage liver disease may offer the opportunity to address these
      modifiable risk factors and prevent disease progression in these patients.

PMID- 24274872
TI  - The impact of obesity and metabolic syndrome on chronic hepatitis B and drug
      induced liver disease.
AB  - Steatosis and insulin resistance (IR) are no more frequent in chronic hepatitis B
      (CHB) than in the general population. Although experimental studies suggest that
      the HBx protein induces liver fat, human studies have shown that steatosis and IR
      are related to coexistent metabolic risk factors, thus epidemiologically linked
      rather than virally induced. Diabetes and obesity are associated with advanced
      fibrosis and increased risk of hepatocellular carcinoma in CHB. Despite abundant
      experimental data showing that fatty liver is more susceptible to liver injury,
      drug-induced liver disease seems no more frequent in NAFLD patients, except,
      possibly, a higher incidence but not severity of acetaminophen hepatotoxicity. 

PMID- 24274873
TI  - Nutrition in cirrhosis and chronic liver disease.
AB  - Nutrition has not been a primary focus of many medical conditions despite its
      importance in the development and the severity of these diseases. This is
      certainly the case with nutrition and end-stage liver disease despite the well
      established association of nutritional deficiencies and increased rates of
      complications and mortality in cirrhosis. This review provides an overview of
      nutrition in chronic liver disease with an emphasis on its pathogenesis as well
      as ways to assess nutritional status and intervene in an effort to improve
      nutrition. 

PMID- 24274874
TI  - Obesity and liver cancer.
AB  - Obesity is an established risk factor for many types of cancers, particularly for
      hepatocellular carcinoma (HCC), owing to its carcinogenic potential and the
      association with nonalcoholic fatty liver disease (NAFLD). HCC may develop in
      cirrhotic and noncirrhotic livers with NAFLD, particularly in the presence of
      multiple metabolic risk factors such as obesity and diabetes. This issue is
      alarming because the population potentially at higher risk is greatly increasing.
      This review summarizes current evidence linking obesity and liver cancer, and
      discusses recent advances on the mechanisms underlying this relationship.

PMID- 24274875
TI  - Impact of nutrition and obesity on chronic liver disease.
AB  - Undernutrition and obesity are at opposite ends of a spectrum that has an
      enormous impact on all aspects of liver diseases. The myriad effects of the
      opposing ends of the nutrition spectrum have led to a wealth of research aimed at
      elucidating the exact mechanisms of how they cause liver damage. In this article,
      the role of the liver in nutrient and energy metabolism is discussed, as well as
      the known and possible effects of specific nutrient deficiencies and obesity.

PMID- 24274877
TI  - The interactions of nonalcoholic fatty liver disease and cardiovascular diseases.
AB  - A complex interaction among metabolic factors, adipose tissue lipolysis,
      oxidative stress, and insulin resistance results in a deleterious process that
      may link nonalcoholic fatty liver disease (NAFLD) with severe cardiovascular (CV)
      outcomes. Patients with NAFLD are at higher risk of atherosclerosis, new onset of
      CV events, and overall mortality. The strong association between NAFLD and CV
      disease should affect clinical practice, with screening and surveillance of
      patients with NAFLD. This review discusses the data linking these major diseases.

PMID- 24274876
TI  - Obesity, nutrition, and liver disease in children.
AB  - In this article, several aspects of childhood obesity are discussed, including
      epidemiology, associated metabolic complications, management strategies, and
      therapy with particular attention to the impact of obesity on the liver,
      resulting in nonalcoholic or metabolic fatty liver disease. The deleterious
      effects of obesity on the liver and health overall can be significantly impacted
      by a culture that fosters sustained nutritional improvement and regular physical
      activity. The current evidence is summarized supporting pharmacologic,
      behavioral, and dietary interventions for the management of obesity and fatty
      liver disease in children.

PMID- 24274878
TI  - Host genetic variants in obesity-related nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a complex disease. The considerable
      variability in the natural history of the disease suggests an important role for
      genetic variants in the disease development and progression. There is evidence
      based on genome-wide association studies and/or candidate gene studies that
      genetic polymorphisms underlying insulin signaling, lipid metabolism, oxidative
      stress, fibrogenesis, and inflammation can predispose individuals to NAFLD. This
      review highlights some of the genetic variants in NAFLD.

PMID- 24274879
TI  - Obesity and liver disease.

PMID- 24274880
TI  - Platinum(II)-catalyzed asymmetric ring-opening addition of arylboronic acids to
      oxabenzonorbornadienes.
AB  - A new platinum(II)-catalyzed asymmetric ring-opening addition of arylboronic
      acids to oxabenzonorbornadienes was developed, which afforded the corresponding
      cis-2-aryl-1,2-dihydronaphthalen-1-ol products in high yields (up to 97%) with
      moderate to good enantioselectivities (up to 89% ee) under very mild conditions.
      The effects of various ligands, catalyst loading, bases, solvents, and
      temperatures on the yield and enantioselectivity of the reaction were also
      investigated. The cis configuration of product 2m was confirmed by X-ray
      diffraction analysis. A potential mechanism for the present catalytic reaction is
      proposed. 

PMID- 24274882
TI  - Power of treatment success definitions when the Canine Brief Pain Inventory is
      used to evaluate carprofen treatment for the control of pain and inflammation in
      dogs with osteoarthritis.
AB  - OBJECTIVE: To determine the optimal method for use of the Canine Brief Pain
      Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment
      with carprofen or placebo. ANIMALS: 150 dogs with osteoarthritis. PROCEDURES:
      Data were analyzed from 2 studies with identical protocols in which owner
      completed CBPIs were used. Treatment for each dog was classified as a success or
      failure by comparing the pain severity score (PSS) and pain interference score
      (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was
      defined on the basis of various combinations of reduction in the 2 scores when
      inclusion criteria were set as a PSS and PIS >= 1, 2, or 3 at baseline.
      Statistical analyses were performed to select the definition of treatment success
      that had the greatest statistical power to detect differences between carprofen
      and placebo treatments. RESULTS: Defining treatment success as a reduction of >=
      1 in PSS and >= 2 in PIS in each dog had consistently robust power. Power was
      62.8% in the population that included only dogs with baseline scores >= 2 and
      64.7% in the population that included only dogs with baseline scores >= 3.
      CONCLUSIONS AND CLINICAL RELEVANCE: The CBPI had robust statistical power to
      evaluate the treatment effect of carprofen in dogs with osteoarthritis when
      protocol success criteria were predefined as a reduction >= 1 in PIS and >= 2 in
      PSS. Results indicated the CBPI can be used as an outcome measure in clinical
      trials to evaluate new pain treatments when it is desirable to evaluate success
      in individual dogs rather than overall mean or median scores in a test
      population.

PMID- 24274883
TI  - Digital image analysis of rhodanine-stained liver biopsy specimens for
      calculation of hepatic copper concentrations in dogs.
AB  - OBJECTIVE: To evaluate the accuracy of digitally scanned rhodanine-stained liver
      biopsy specimens for determination of hepatic copper concentration and compare
      results with qualitatively assigned histologic copper scores in dogs. SAMPLE: 353
      liver biopsy specimens from dogs. PROCEDURES: Specimens (n = 139) with quantified
      copper concentration ranging from 93 to 6,900 MUg/g were allocated to group 1 (<
      400 MUg/g [37]), group 2 (401 to 1,000 MUg/g [27]), group 3 (1,001 to 2,000 MUg/g
      [34]), and group 4 (> 2,001 MUg/g [41]); stained with rhodanine; and digitally
      scanned and analyzed with a proprietary positive pixel algorithm. Measured versus
      calculated copper concentrations were compared, and limits of agreement
      determined. Influence of nodular remodeling, fibrosis, or parenchymal loss on
      copper concentration was determined by digitally analyzing selected regions in 17
      specimens. After method validation, 214 additional liver specimens underwent
      digital scanning for copper concentration determination. All sections (n = 353)
      were then independently scored by 2 naive evaluators with a qualitative scoring
      schema. Agreement between assigned scores and between assigned scores and tissue
      copper concentrations was determined. RESULTS: Linear regression was used to
      develop a formula for calculating hepatic copper concentration >= 400 MUg/g from
      scanned sections. Copper concentrations in unremodeled specimens were
      significantly higher than in remodeled specimens. Qualitative scores widely
      overlapped among quantitative copper concentration groups. CONCLUSIONS AND
      CLINICAL RELEVANCE: Calculated copper concentrations determined by means of
      digital scanning of rhodanine-stained liver sections were highly correlated with
      measured values and more accurate than qualitative copper scores, which should
      improve diagnostic usefulness of hepatic copper concentrations and assessments in
      sequential biopsy specimens.

PMID- 24274884
TI  - Microvasculature of the suspensory ligament of the forelimb of horses.
AB  - OBJECTIVE: To determine the microvascular anatomy of the suspensory ligament of
      the forelimb of horses. SAMPLE: 17 cadaveric forelimbs from 9 adult horses with
      no known history of forelimb lameness. PROCEDURES: The median artery of the
      forelimb was cannulated proximal to the antebrachiocarpal joint and injected with
      contrast medium for CT evaluation of the gross vasculature (n = 2) or India ink
      to evaluate the microvasculature (12). Routine histologic evaluation was
      performed on an additional 3 forelimbs to confirm the microvascular anatomy.
      RESULTS: The vascular supply of the suspensory ligament of the forelimb
      originated from branches of the medial and lateral palmar and palmar metacarpal
      vessels as well as the proximal and distal deep palmar arches. An abundant,
      longitudinally oriented microvascular supply was evident throughout the length of
      the suspensory ligament without distinct variation among the proximal, midbody,
      and distal regions. The intraligamentous blood supply originated from a
      periligamentous vascular plexus that surrounded the suspensory ligament
      throughout its length. Histologic findings indicated the presence of a
      periligamentous connective tissue plexus, which contained vessels that penetrated
      and anastomosed with an extensive network of intraligamentous vessels throughout
      the length of the suspensory ligament. CONCLUSIONS AND CLINICAL RELEVANCE: The
      suspensory ligament of the equine forelimb had an abundant intraligamentous
      microvascular supply throughout its entire length. The absence of an obvious
      hypovascular area suggested that regional variations in healing rates of the
      suspensory ligament are not associated with the microvascular anatomy.

PMID- 24274885
TI  - Effect of configuration on the biomechanical performance of three suture
      materials used in combination with a metallic bone anchor.
AB  - OBJECTIVE: To determine whether different suture configurations could improve the
      biomechanical performance of 3 suture materials used with bone anchors. SAMPLES:
      3 suture materials (60-lb test nylon leader line, size 2 polyblend polyethylene
      composite suture, and 150-lb test ultrahigh-molecular weight spun polyethylene).
      PROCEDURES-Each suture material was looped through the eyelet of a metallic bone
      anchor and constructs were evaluated by use of an acute uniaxial load. Three
      configurations were tested for each suture material: single stranded (SS), double
      stranded (DS), and single stranded plus plastic insert (SSP). Force at failure,
      extension at failure, force at 3 mm of extension, stiffness, and site of failure
      of the suture were recorded for each test. RESULTS: For all sutures, the DS
      configuration was the stiffest and yielded significantly higher forces at failure
      and forces at 3 mm of extension. The SS configuration had the lowest forces at
      failure. The SSP configuration yielded greater forces at failure for all suture
      materials, compared with the SS configuration, with a comparable stiffness. All
      sutures failed at the eyelet in the SS and DS configurations. In the SSP
      configuration, 60-lb test nylon leader line and 150-lb test ultrahigh-molecular
      weight spun polyethylene failed at the eyelet less frequently than did the
      polyblend composite suture. CONCLUSIONS AND CLINICAL RELEVANCE: Among the tested
      constructs, a DS suture configuration used in combination with the metallic bone
      anchor gave the best biomechanical results for all suture materials. Considering
      that the SSP configuration yielded greater forces at failure, compared with the
      SS configuration, covering metallic edges in bone anchors with softer materials
      might protect sutures and result in increased forces at failure.

PMID- 24274886
TI  - Evaluation and modification of the overall hemostasis potential assay for use
      with canine plasma.
AB  - OBJECTIVE: To optimize the overall hemostasis potential (OHP) assay for use with
      canine platelet-poor plasma and determine reference intervals in healthy dogs.
      ANIMALS: 40 healthy dogs. PROCEDURES: Blood was collected from the dogs into
      citrated tubes, and platlet-poor plasma was obtained. The OHP assay and standard
      coagulation assays (prothrombin time, activated partial thromboplastin time, and
      fibrinogen concentration) were performed for each sample. The OHP assay outputs
      were tested for correlations with results of the standard coagulation assays,
      age, and sex. RESULTS: Modifications to the published methodology for the OHP
      assay were required for use with canine plasma, with less coagulation activator
      (thrombin) and more fibrinolysis activator (tissue plasminogen activator) than
      used with human plasma. Male dogs had a higher OHP than did females. High
      fibrinogen concentrations were associated with increases in maximum optical
      density, OHP, and overall coagulation potential, and reduced prothrombin time was
      associated with increases in maximum optical density, overall coagulation
      potential, OHP, and maximum slope. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      supported the use of the OHP assay as an accessible, cost-effective global
      coagulation assay. Further research is required to determine its clinical
      application as an alternative to thromboelastography or thrombin generation
      assays.

PMID- 24274887
TI  - Inoculation of dogs with a recombinant ACTH vaccine.
AB  - OBJECTIVE: To determine whether inoculation of healthy dogs with a recombinant
      peptide containing 3 copies of ACTH would result in the production of antibodies
      against ACTH and whether this would affect pituitary-adrenocortical function.
      ANIMALS: 8 healthy dogs. PROCEDURES: A recombinant peptide consisting of 3 copies
      of ACTH fused to a T-helper cell epitope was produced in Escherichia coli. The
      protein was inoculated into 4 dogs at 4-week intervals (total of 3
      inoculations/dog). Four control dogs received inoculations of PBS solution mixed
      with adjuvant. Blood samples were collected for determination of antibody titers
      against ACTH and for measurement of basal and ACTH-stimulated plasma cortisol
      concentrations. RESULTS: Inoculation with the ACTH vaccine resulted in production
      of anti-ACTH antibodies in all 4 dogs. Titers were initially high but declined by
      15 weeks after the initial inoculation. Basal cortisol concentrations were
      unaffected by inoculation with the ACTH vaccine. Plasma cortisol concentrations
      in response to ACTH stimulation were reduced at 12 weeks, but not at 15 weeks,
      after the first inoculation. CONCLUSIONS AND CLINICAL RELEVANCE: Inoculation of
      dogs with a recombinant ACTH vaccine resulted in the production of antibodies
      against the hormone. Anti-ACTH titers were initially high but were not sustained.
      The only detectable endocrine effect in treated dogs was a reduction in cortisol
      concentration in response to ACTH stimulation in 2 of 4 dogs at 12 weeks after
      the first inoculation. The effect of vaccine administration on the pituitary
      adrenal system was subtle and transient.

PMID- 24274888
TI  - Short-term effect of ovariectomy on measures of insulin sensitivity and response
      to dexamethasone administration in horses.
AB  - OBJECTIVE: To evaluate the effect of ovariectomy on insulin sensitivity in horses
      and determine whether the effects of suppression of the hypothalamo-pituitary
      adrenal axis differ before and after ovariectomy. ANIMALS: 6 healthy mares.
      PROCEDURES: The horses underwent an IV glucose tolerance test (IVGTT), an insulin
      sensitivity test, and a dexamethasone suppression test before and 5 weeks after
      ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum
      insulin-to-blood glucose concentration ratios, and changes in blood glucose
      concentration with time after injection of glucose or insulin were compared
      before and after ovariectomy. RESULTS: The dexamethasone injection resulted in a
      decrease in serum cortisol concentration before and after ovariectomy. In all
      horses, baseline plasma ACTH concentrations were within the reference range
      before and after ovariectomy. For each mare, results of an IVGTT before and after
      ovariectomy were considered normal. No significant differences in basal blood
      glucose concentration or time to reach baseline glucose concentration after an
      IVGTT were observed. Basal serum insulin concentration and serum insulin-to-blood
      glucose concentration ratios were not significantly different before or after
      ovariectomy, nor was the mean time to attain a 50% decrease in blood glucose
      concentration after insulin injection. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that ovariectomy does not appear to modify dexamethasone
      response in horses and that it does not modify short-term measures of insulin
      sensitivity. Findings suggested that horses undergoing ovariectomy are not at
      higher risk of developing equine metabolic syndrome or hypothalamo-pituitary
      adrenal axis dysfunction and associated morbidity.

PMID- 24274889
TI  - Assessment of calcitonin response to experimentally induced hypercalcemia in
      cats.
AB  - OBJECTIVE: To characterize the dynamics of calcitonin secretion in response to
      experimentally induced hypercalcemia in cats. ANIMALS: 13 healthy adult European
      Shorthair cats. PROCEDURES: For each cat, the calcitonin response to
      hypercalcemia (defined as an increase in ionized calcium concentration > 0.3 mM)
      was investigated by infusing calcium chloride solution and measuring circulating
      calcitonin concentrations before infusion (baseline) and at various ionized
      calcium concentrations. Calcitonin expression in the thyroid glands of 10 of the
      cats was investigated by immunohistochemical analysis. RESULTS: Preinfusion
      baseline plasma calcitonin concentrations were very low in many cats, sometimes
      less than the limit of detection of the assay. Cats had a heterogeneous
      calcitonin response to hypercalcemia. Calcitonin concentrations only increased in
      response to hypercalcemia in 6 of 13 cats; in those cats, the increase in
      calcitonin concentration was quite variable. In cats that responded to
      hypercalcemia, calcitonin concentration increased from 1.3 +/- 0.3 pg/mL at
      baseline ionized calcium concentration to a maximum of 21.2 +/- 8.4 pg/mL at an
      ionized calcium concentration of 1.60 mM. Cats that did not respond to
      hypercalcemia had a flat calcitonin-to-ionized calcium concentration curve that
      was not modified by changes in ionized calcium concentration. A significant
      strong correlation (r = 0.813) was found between the number of calcitonin
      positive cells in the thyroid gland and plasma calcitonin concentrations during
      hypercalcemia. CONCLUSIONS AND CLINICAL RELEVANCE: Healthy cats had very low
      baseline plasma calcitonin concentrations. A heterogeneous increase in plasma
      calcitonin concentration in response to hypercalcemia, which correlated with the
      expression of calcitonin-producing cells in the thyroid, was identified in cats.

PMID- 24274890
TI  - Evaluation of endocrine and immune responses of steers challenged with infectious
      bovine rhinotracheitis virus.
AB  - OBJECTIVE: To evaluate the endocrine and immune responses of steers challenged
      with infectious bovine rhinotracheitis virus (IBRV). ANIMALS: 12 crossbred beef
      steers. PROCEDURES: Steers were randomly assigned to IBRV- (control) or IBRV+
      treatment groups. Experimentally challenged steers (IBRV+) received a dose of
      IBRV intranasally (8.0 50% tissue culture infective doses), IBRV- steers received
      a saline (0.9% NaCl) solution placebo intranasally, and each group was placed in
      an isolated paddock. At 72 hours after challenge, all steers were fitted with
      indwelling jugular catheters and placed into individual stanchions. Blood samples
      were collected on days 4 through 8. Serum was analyzed for concentrations of
      cortisol, interleukin-6, interferon-gamma, tumor necrosis factor-alpha, growth
      hormone, and insulin-like growth factor I. RESULTS: From 72 to 144 hours after
      challenge inoculation, the IBRV+ group had significantly greater mean rectal
      temperature, compared with the IBRV- group; the greatest temperatures in both
      groups were observed at 72 hours. Serum cortisol concentrations were increased in
      both groups from hours 72 to 136 and serum interferon-gamma concentrations were
      greater in the IBRV+ from 94 to 112 hours after inoculation. Growth hormone
      concentration was greater in the IBRV+ group at various time points, but no
      difference in insulin-like growth factor- I concentration was observed.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that IBVR challenge altered
      growth hormone concentration at some time points but was not associated with
      large increases in circulating proinflammatory cytokines.

PMID- 24274891
TI  - Effects of quaternary benzo(c)phenanthridine alkaloids on growth performance,
      shedding of organisms, and gastrointestinal tract integrity in pigs inoculated
      with multidrug-resistant Salmonella spp.
AB  - OBJECTIVE: To evaluate effects of quaternary benzo(c)phenanthridine alkaloids
      (QBAs) against Salmonella spp and determine effects on growth performance,
      organism shedding, and gastrointestinal tract integrity in pigs inoculated with
      Salmonella enterica serovar Typhimurium. SAMPLE: 36 Salmonella isolates and
      twenty 5-week-old pigs. PROCEDURES: Minimum inhibitory concentration of QBAs
      against the Salmonella isolates was determined. Pigs were allocated to 4 groups
      and inoculated with Salmonella organisms. Pigs received diets supplemented with
      1.5 g of QBAs/1,000 kg of feed, 0.75 g of QBAs/1,000 kg of feed, or 59.4 g of
      chlortetracycline/1,000 kg of feed or a nonsupplemented (control) diet. Pigs were
      weighed on day 0 and then weekly for 40 days. Fecal samples were collected to
      quantify Salmonella organisms. Gastrointestinal tract integrity was evaluated by
      measuring transepithelial resistance. RESULTS: In vitro, 9 of 36 (25%) Salmonella
      isolates were inhibited at 90 MUg of QBAs/mL; all 36 were inhibited at 179 MUg of
      QBAs/mL. Diets containing QBAs significantly decreased Salmonella spp shedding;
      shedding was lower 40 days after inoculation for pigs fed diets containing QBAs
      or chlortetracycline than for pigs fed the control diet. Growth performance was
      similar for pigs fed diets containing QBA or chlortetracycline. Gastrointestinal
      tract integrity was improved in pigs fed the diet containing 1.5 g of QBAs/1,000
      kg of feed. CONCLUSIONS AND CLINICAL RELEVANCE: QBAs and chlortetracycline
      decreased Salmonella spp shedding but did not differ with regard to growth
      performance. Gastrointestinal tract integrity was better, albeit not
      significantly, in pigs fed diets containing QBAs. Further investigation into the
      role of QBAs and their mechanism as an immunomodulator is necessary.

PMID- 24274892
TI  - Collection and characterization of semen from green iguanas (Iguana iguana).
AB  - OBJECTIVE: To determine an efficient method for the collection of semen samples
      by means of electroejaculation, characterize spermatozoa quality and quantity,
      and determine the effect of refrigerated storage on motility of spermatozoa
      obtained from green iguanas (Iguana iguana). ANIMALS: 18 adult green iguanas.
      PROCEDURES: Green iguanas were anesthetized, and semen samples were obtained by
      means of electroejaculation. Up to 3 series of electrostimulations were
      performed; the procedure was stopped after a semen sample was obtained. Various
      semen sample variables were evaluated. RESULTS: Semen samples were obtained from
      16 iguanas; most (n = 10) iguanas produced a semen sample after the second series
      of electrostimulations. Median semen sample volume was 0.05 mL. Mean spermatozoa
      concentration was 2 69.0 * 10(6) spermatozoa/mL. Median percentage of motile
      spermatozoa was 78%. The only morphological abnormality of spermatozoa was bent
      tails (mean percentage in a semen sample, 5.7%). Spermatozoa motility decreased
      significantly during refrigeration (4 degrees C); median percentage motility
      after 24, 48, and 72 hours of refrigeration was 60%, 33%, and 0%, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested
      electroejaculation can be performed to collect semen samples from green iguanas,
      characteristics of iguana semen samples are similar to those for semen samples
      obtained from other reptiles, and motility of iguana spermatozoa decreases during
      refrigeration within 48 to 72 hours.

PMID- 24274893
TI  - Association between urine osmolality and specific gravity in dogs and the effect
      of commonly measured urine solutes on that association.
AB  - OBJECTIVE: To determine the association between urine osmolality and specific
      gravity (USG) in dogs and to evaluate the effect of commonly measured urine
      solutes on that association. ANIMALS: 60 dogs evaluated by an internal medicine
      service. PROCEDURES: From each dog, urine was obtained by cystocentesis and USG
      was determined with a refractometer. The sample was divided, and one aliquot was
      sent to a diagnostic laboratory for urinalysis and the other was frozen at -80
      degrees C until osmolality was determined. Urine samples were thawed and
      osmolality was measured in duplicate with a freezing-point depression osmometer.
      The correlation between mean urine osmolality and USG was determined; the effect
      of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on
      this relationship was investigated with multiple regression analysis. RESULTS:
      The Pearson correlation coefficient between urine osmolality and USG was 0.87.
      The final multivariable regression model for urine osmolality included USG and
      the presence of ketones; ketonuria had a small negative association with urine
      osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a strong linear
      correlation between osmolality and USG in urine samples obtained from dogs with
      various pathological conditions, and ketonuria had a small negative effect on
      that correlation.

PMID- 24274894
TI  - Prevalence of extended spectrum beta lactamase producing Escherichia coli and
      Klebsiella pneumoniae urinary isolates in a tertiary care hospital in Kathmandu,
      Nepal.
AB  - BACKGROUND: Escherichia coli and Klebsiella pneumoniae are the major bacterial
      pathogens being isolated and reported from mid stream urine (MSU) specimens,
      globally. These uropathogens are mostly implicated as the major extended spectrum
      beta-lactamase (ESBL) producers, severely limiting the therapeutic management in
      cases of urinary tract infections. Limited studies had been reported from Nepal
      investigating the ESBL producers among uropathogens. This study was designed to
      assess the prevalence of ESBL producing E.coli and K. pneumoniae in urinary
      isolates at a centrally located major tertiary care hospital in Kathmandu valley,
      Nepal. METHODS: Between September 2011 and May 2012, during the nine months
      period, 6308 MSU specimens were collected aseptically from the same number of
      clinically suspected patients of urinary tract infections. The samples were
      cultured on MacConkey agar and blood agar. The isolates with significant
      bacteriuria (105 CFU / ml) were identified based on standard laboratory
      procedures. Antimicrobial susceptibility tests were carried out using various
      antimicrobial discs alongwith ceftriaxone on E.coli and K. pneumoniae isolates by
      Kirby Bauer disc diffusion method as per the recommendations of CLSI. On initial
      screening with ceftriaxone (30 MUg) disc showing resistance was then confirmed
      for ESBL production by phenotypic confirmatory disc diffusion test (PCDDT) using
      ceftazidime (30 ug) and ceftazidime + clavulanic acid (30 MUg + 10ug) disc as per
      guidelines of CLSI (2011). RESULTS: Out of a total of 6308 MSU specimens
      investigated for significant bacteriuria, E.coli isolates were 444 (7.04%) and
      K.pneuminiae were 145 (2.3%) making a total of 589 (9.34%). Initial screening
      with ceftriaxone disc revealed 155 isolates of E.coli and 70 isolates of
      K.pneumoniae to be resistant. Further testing by PCDDT method showed 60/444
      (=13.51%) of E. coli and 24/145 (=16.55%) of K. pneumoniae isolates to be
      confirmed ESBL producers. These ESBL - producer uropathogens showed high degree
      of resistance to ceftriaxone (100.0%), amoxycillin, fluoroquinolones and co
      trimoxazole. CONCLUSION: An emerging and moderately high prevalence of ESBL
      producing E. coli and K. pneumoniae was observed and confirmed in the urinary
      isolates investigated. It is essential to have a regular and routine monitoring
      of ESBL producing clinical isolates in laboratory practice.

PMID- 24274895
TI  - Exploring physical exposures and identifying high-risk work tasks within the
      floor layer trade.
AB  - INTRODUCTION: Floor layers have high rates of musculoskeletal disorders yet few
      studies have examined their work exposures. This study used observational methods
      to describe physical exposures within floor laying tasks. METHODS: We analyzed 45
      videos from 32 floor layers using Multimedia-Video Task Analysis software to
      determine the time in task, forces, postures, and repetitive hand movements for
      installation of four common flooring materials. We used the WISHA checklists to
      define exposure thresholds. RESULTS: Most workers (91%) met the caution threshold
      for one or more exposures. Workers showed high exposures in multiple body parts
      with variability in exposures across tasks and for different materials. Prolonged
      exposures were seen for kneeling, poor neck and low back postures, and
      intermittent but frequent hand grip forces. CONCLUSIONS: Floor layers experience
      prolonged awkward postures and high force physical exposures in multiple body
      parts, which probably contribute to their high rates of musculoskeletal
      disorders.

PMID- 24274896
TI  - Acute Toxoplasma gondii infection among family members in the United States.
AB  - We investigated 32 families of persons with acute toxoplasmosis in which > or = 1
      other family member was tested for Toxoplasma gondii infection; 18 (56%) families
      had > or = 1 additional family member with acute infection. Family members of
      persons with acute toxoplasmosis should be screened for infection, especially
      pregnant women and immunocompromised persons.

PMID- 24274897
TI  - Highly uniform hole spacing micro brushes based on aligned carbon nanotube
      arrays.
AB  - Highly uniform hole spacing micro brushes were fabricated based on aligned carbon
      nanotube (CNT) arrays synthesized by chemical vapor deposition method with the
      assistance of anodic aluminum oxide (AAO) template. Different micro brushes from
      CNT arrays were constructed on silicon, glass, and polyimide substrates,
      respectively. The micro brushes had highly uniform hole spacing originating from
      the regularly periodic pore structure of AAO template. The CNT arrays, serving as
      bristles, were firmly grafted on the substrates. The brushes can easily clean
      particles with scale of micrometer on the surface of silicon wafer and from the
      narrow spaces between the electrodes in a series of cleaning experiments. The
      results show the potential application of the CNT micro brushes as a cleaning
      tool in microelectronics manufacture field. 

PMID- 24274898
TI  - New Delhi metallo-beta-lactamase-1 in carbapenem-resistant Salmonella strain,
      China.

PMID- 24274899
TI  - Tupichinins B-D, three new spirostanol saponins from Tupistra chinensis rhizomes.
AB  - Three new spirostanol saponins were isolated from the EtOAc fraction of methanol
      extract from Tupistra chinensis rhizomes. Based on the detailed analysis of their
      1D and 2D NMR spectra and chemical evidence, their structures were determined as
      1beta-O-acetyl-spirost-5,25(27)-dien-3alpha-yl-O-beta-D-glucopyranoside (1),
      (25S)-1beta,2beta,5beta-trihydroxy-spirostane-3beta-yl-O-beta-D-glucopyranoside
      (2) and (25S)-1beta,2beta-dihydroxy-5beta-spirostane-3beta-yl-O-beta-D
      xylopyranoside (3), respectively.

PMID- 24274900
TI  - High Hemoglobin A1c levels and glycemic variability increase risk of severe
      hypoglycemia in diabetic hemodialysis patients.
AB  - While hyperglycemia is central to the pathogenesis and management of diabetes
      mellitus, hypoglycemia and glucose variability also contribute to outcomes. We
      previously reported on the relationship of glycemic control to outcomes in a
      large population of diabetic end-stage renal disease (ESRD) patients. Recognizing
      that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the
      association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic
      variability in those with hypoglycemia. This is a retrospective study of patients
      with diabetes enrolled in a large hemodialysis program. Hypoglycemia was
      identified from hospital discharge diagnostic codes. Glycemic variability was
      assessed by the standard deviation of HgbA1c and glucose levels over time.
      Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher
      baseline HgbA1c was associated with greater risk for hypoglycemia
      hospitalization, a finding confirmed by time-lagged HgbA1c levels drawn a quarter
      earlier. Higher baseline HgbA1c categories were also associated with greater
      variability in HgbA1c levels during the analysis period. Similarly, greater
      glucose variability was associated with higher mean glucose levels by trend
      analysis. High, not low, HgbA1c levels are associated with greater risk of severe
      hypoglycemia, which may derive from glucose variability in the setting of
      treatment for hyperglycemia. High HgbA1c and glycemic variability are associated
      with increased risk of hypoglycemia in individuals with diabetes and ESRD. 

PMID- 24274901
TI  - Asking for something different from our donors: factors influencing persuasion
      success.
AB  - BACKGROUND: Demand for plasma-derived products, and consequently plasmapheresis
      donors, continues to increase. This study aims to identify the factors that
      facilitate the persuasion success of conversations with whole blood (WB) donors
      to convert to plasmapheresis donation within a voluntary nonremunerated context.
      STUDY DESIGN AND METHODS: Surveys were sent to WB donors after a plasmapheresis
      conversion conversation with a blood collection agency (BCA) staff member: in
      center (Sample 1) or via a call center (Sample 2). Participants reported the
      number of donor-initiated and BCA-initiated conversations about plasma,
      experienced in the prior 12 months. Perceptions of the most recent conversation,
      donor oriented and conversion oriented, were also reported. The BCA provided WB
      donation history for the prior 5 years. Participants' intentions to make a first
      plasmapheresis donation were captured and any subsequent plasmapheresis donation
      was objectively recorded. RESULTS: Conversion rates were higher for in-center
      than call center-based conversations. For both samples, path analyses revealed
      that intentions are associated with conversion. Prior WB donations are negatively
      associated, while donor-initiated and donor-orientated conversations are
      positively associated with conversion intentions. Results for agent-initiated
      conversations and conversion-orientated conversations were mixed across samples.
      CONCLUSION: Converting suitable WB donors to plasmapheresis is best achieved
      early in the donor's career using face-to-face conversations with collection
      center staff. BCAs should facilitate donor-initiated conversations through
      promotional campaigns that encourage donors to approach staff. Conversations that
      focus on donors' needs and welfare more effectively encourage conversion
      intentions than those perceived as pushing the requirements of the BCA.

PMID- 24274902
TI  - Cross-linking of thioredoxin reductase by the sulfur mustard analogue
      mechlorethamine (methylbis(2-chloroethyl)amine) in human lung epithelial cells
      and rat lung: selective inhibition of disulfide reduction but not redox cycling.
AB  - Oxidative stress plays a key role in mechlorethamine (methylbis(2
      chloroethyl)amine, HN2) toxicity. The thioredoxin system, consisting of
      thioredoxin reductase (TrxR), thioredoxin, and NADPH, is important in redox
      regulation and protection against oxidative stress. HN2 contains two
      electrophilic side chains that can react with nucleophilic sites in proteins,
      leading to changes in their structure and function. We report that HN2 inhibits
      the cytosolic (TrxR1) and mitochondrial (TrxR2) forms of TrxR in A549 lung
      epithelial cells. TrxR exists as homodimers under native conditions; monomers can
      be detected by denaturing and reducing SDS-PAGE followed by western blotting. HN2
      treatment caused marked decreases in TrxR1 and TrxR2 monomers along with
      increases in dimers and oligomers under reducing conditions, indicating that HN2
      cross-links TrxR. Cross-links were also observed in rat lung after HN2 treatment.
      Using purified TrxR1, NADPH reduced, but not oxidized, enzyme was inhibited and
      cross-linked by HN2. LC-MS/MS analysis of TrxR1 demonstrated that HN2 adducted
      cysteine- and selenocysteine-containing redox centers forming monoadducts,
      intramolecule and intermolecule cross-links, resulting in enzyme inhibition. HN2
      cross-links two dimeric subunits through intermolecular binding to cysteine 59 in
      one subunit of the dimer and selenocysteine 498 in the other subunit, confirming
      the close proximity of the N- and C-terminal redox centers of adjacent subunits.
      Despite cross-linking and inhibition of TrxR activity by HN2, TrxR continued to
      mediate menadione redox cycling and generated reactive oxygen species. These data
      suggest that disruption of the thioredoxin system contributes to oxidative stress
      and tissue injury induced by HN2. 

PMID- 24274903
TI  - Study of quality of life in patients with benign prostatic hyperplasia under
      treatment with silodosin.
AB  - OBJECTIVES: To assess the impact of urinary symptoms associated with benign
      prostatic hyperplasia and its treatment with silodosin, on quality of life (QoL)
      and sexual function, depending on age, severity of symptoms, time on treatment
      and prostate size. MATERIAL AND METHODS: A cross-sectional, observational study
      was conducted in 305 urology practices all around Spain. Socio-demographic and
      clinical data were collected and patients filled the following questionnaires: EQ
      5D, Sexual Function Index (SFI) and International Prostate Symptom Score (IPSS).
      Multiple regression models were used to determine factors independently
      associated with patients' QoL. RESULTS: A total of 1,019 patients were enrolled,
      mean (SD) for: age 62.7 (5.7), EQ-5D 89.9 (13.9), sexual drive-SFI 3.71 (1.67),
      erection-SFI 6.11 (3.08), ejaculation-SFI 4.50 (2.06) problems-SFI 6.85 (3.37)
      and overall satisfaction-SFI 2.00 (0.99). The EQ-5D and SFI score were
      statistically lower with: older age, severe LUTS and greater prostate size
      (P<.01), but no differences were found related to time on treatment with
      silodosin. The EQ-5D score was positively associated with sexual satisfaction and
      desire size of SFI and the EQ-5D VAS score, and negatively with disability, semi
      urban residence and comorbidities in the multiple regression analyses.
      CONCLUSIONS: Severe LUTS and older age are associated to a greater deterioration
      in sexual function and quality of life. However time on treatment with silodosin
      does not produce deterioration in the quality of life.

PMID- 24274904
TI  - Hand function and quality of life in children with epidermolysis bullosa.
AB  - Patient-reported outcomes are becoming increasingly important to clinical care.
      Epidermolysis bullosa (EB), a rare genetic skin disorder, can result in severe
      hand impairment, but parent and patient perceptions of hand function have never
      been assessed. This study aimed to quantify parent- and patient-reported hand
      function and assess its relationship with quality of life (QOL) in children with
      EB. This cross-sectional study included children with EB treated at an
      interdisciplinary EB center. Hospital records were searched for demographic
      characteristics and medical history. Eligible families were invited to complete
      two surveys by mail or telephone. The ABILHAND-Kids questionnaire assessed manual
      hand ability for 21 functions. The Quality of Life in Epidermolysis Bullosa
      questionnaire assessed EB-related QOL. Hand function and QOL of various subtypes
      were compared using Mann-Whitney tests. Seventy-one parents and patients ages 2
      to 18 years with EB from 20 states in the United States completed questionnaires.
      Children with recessive dystrophic EB reported the worst hand function and QOL.
      Bimanual functions involving finger mobility were the most challenging for all EB
      subtypes. QOL was highly related to the degree of hand function, being correlated
      with 20 of the 21 individual hand functions and most associated with the ability
      to perform unimanual functions. Parent- and patient-reported hand function can be
      measured in children with EB using the ABILHAND-Kids questionnaire. Hand
      impairment is strongly associated with worse QOL, probably due to difficulty
      performing daily activities. The effect of interventions such as hand surgery
      could be prospectively evaluated using this questionnaire. 

PMID- 24274905
TI  - Cage shrinkage of fullerene via a C2 loss: from IPR C90(28)Cl24 to nonclassical,
      heptagon-containing C88Cl22/24.
AB  - A new case of chlorination-promoted fullerene cage shrinkage is reported.
      Chlorination of C90 (isolated pentagon rule isomer no. 28) with VCl4 afforded
      C88Cl22 with a nonclassic carbon cage (NCC) containing 1 heptagon and 13
      pentagons including 2 fused pairs flanking the heptagon. The pathway of C2
      abstraction from the C90 cage is suggested on the basis of density functional
      theory calculations. 

PMID- 24274906
TI  - Development of an ELISA assay for the quantification of soluble huntingtin in
      human blood cells.
AB  - BACKGROUND: Huntington's disease (HD) is a monogenic disorder caused by an
      aberrant expansion of CAG repeats in the huntingtin gene (HTT). Pathogenesis is
      associated with expression of the mutant (mHTT) protein in the CNS, with its
      levels most likely related to disease progression and symptom severity. Since non
      invasive methods to quantify HTT in the CNS do not exist, measuring amount of
      soluble HTT in peripheral cells represents an important step in development of
      disease-modifying interventions in HD. RESULTS: An ELISA assay using commercially
      available antibodies was developed to quantify HTT levels in complex matrices
      like mammalian cell cultures lysates and human samples. The immunoassay was
      optimized using a recombinant full-length HTT protein, and validated both on wild
      type and mutant HTT species. The ability of the assay to detect significant
      variations of soluble HTT levels was evaluated using an HSP90 inhibitor that is
      known to enhance HTT degradation. Once optimized, the bioassay was applied to
      peripheral blood mononuclear cells (PBMCs) from HD patients, demonstrating good
      potential in tracking the disease course. CONCLUSIONS: The method described here
      represents a validated, simple and rapid bio-molecular assay to evaluate soluble
      HTT levels in blood cells as useful tool in disease and pharmacodynamic marker
      identification for observational and clinical trials.

PMID- 24274907
TI  - Systemic administration of fluoro-gold for the histological assessment of
      vascular structure, integrity and damage.
AB  - Fluoro-Gold (F-G) has been used extensively as a fluorescent retrograde neuronal
      track tracer in the past. We now report that intraperitoneal administration of 10
      to 30 mg/ kg of F-G from 30 min to 7 days prior to sacrifice labels vascular
      endothelial cells of the brain, choroid plexus and meninges and can be used to
      assess vascular integrity and damage. F-G vascular labeling co-localized with rat
      endothelial cell antigen (RECA-1) in the membrane. F-G also intensely labeled the
      nuclei of the endothelial cells, and co-localized with propidium iodide staining
      of these nuclei. As well, the administration of F-G during neurotoxic insults
      produced by amphetamine, kainic acid or "penetrating" wound to the brain can
      detect where vascular leakage/ hemorrhage has occurred. Histological methods to
      detect F-G labeled brain vasculature were performed in the same manner as that
      used for fluorescent visualization of neuronal elements labeled with F-G after
      perfusion fixation and coronal sectioning (15 to 40 um) of the brain. This in
      vivo F-G labeling of endothelial cells and their nuclei yields a clear picture of
      the integrity of the vasculature and can be used to detect changes in structure.
      Vascular leaks after "penetrating" wounds through the cortex and striatum,
      hyperthermic amphetamine exposure or excitotoxic kainate exposure were detected
      by F-G in the extracellular space and via parenchymal F-G subsequently labeling
      the terminals and neurons adjacent to the lesioned or damaged vasculature.
      Further studies are necessary to determine the extent of the leakage necessary to
      detect vasculature damage. Visualization of the F-G labeling of vasculature
      structure and leakage is compatible with standard fluorescent immuno-labeling
      methods used to detect the presence and distribution of a protein in histological
      sections. This method should be directly applicable to studying brain vascular
      damage that occurs in the progression of Alzheimer's disease, diabetes and for
      monitoring the brain vascular changes during development. 

PMID- 24274908
TI  - Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's
      disease.
AB  - Although selective neurodegeneration of nigro-striatal dopaminergic neurons is
      widely accepted as a cause of Parkinson's disease (PD), the role of vascular
      components in the brain in PD pathology is not well understood. However, the
      neurodegeneration seen in PD is known to be associated with neuroinflammatory
      like changes that can affect or be associated with brain vascular function. Thus,
      dysfunction of the capillary endothelial cell component of neurovascular units
      present in the brain may contribute to the damage to dopaminergic neurons that
      occurs in PD. An animal model of PD employing acute, sub-acute and chronic
      exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to
      determine the extent to which brain vasculature may be damaged in PD. Fluoro
      Turquoise gelatin labeling of microvessels and endothelial cells was used to
      determine the extent of vascular damage produced by MPTP. In addition, tyrosine
      hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic
      neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was
      evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced
      TH immunoreactive neurons in the SNc (20.68 +/- 2.83 in acute; 22.98 +/- 2.14 in
      sub-acute; 10.20 +/- 2.24 in chronic vs 34.88 +/- 2.91 in controls; p<0.001).
      Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of
      MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease
      in the intensity, length, and number of vessels in both CPu and SNc. Degenerative
      vascular changes such as endothelial cell 'clusters' were also observed after
      MPTP suggesting that vasculature damage may be modifying the availability of
      nutrients and exposing blood cells and/or toxic substances to neurons and glia.
      In summary, vascular damage and degeneration could be an additional exacerbating
      factor in the progression of PD, and therapeutics that protect and insure
      vascular integrity may be novel treatments for PD.

PMID- 24274909
TI  - Age-related vascular differences among patients suffering from multiple
      sclerosis.
AB  - The aim of our study was to analyze morphological and functional aspects of
      cerebral veins by means of ecocolor-Doppler in young (i.e., <= 30 years old) and
      older (i.e., >30 years old) patients suffering from multiple sclerosis. 552
      multiple sclerosis patients were evaluated by means of a dedicated Echo-Color
      Doppler support (MyLab Vinco echocolor Doppler System, Esaote), in both supine
      and sitting positions. 458 (83%) showed alterations in their morphological and
      functional structures of cerebral veins and were divided in two different groups:
      1) <= 30 (110 patients) and 2) >30 years old (348 patients). Young patients
      showed a statistically significant higher number of both hemodynamically (44% vs.
      35%, p<0.01) and non-hemodynamically (51% vs. 45%, p<0.05) significant stenosis
      in the internal jugular veins as compared to older patients. A lower percentage
      of young patients showed blocked outflow in the cervical veins (50% vs. 65%,
      p<0.01) as compared to older ones. Patients >30 years old outlined a
      significantly higher disability degree (Expanded Disability Status Scale score: 5
      vs. 3, p<0.01) as well as higher disease duration (12 vs. 5 months, p<0.01) than
      younger. No differences could be outlined about multiple sclerosis clinical form
      of the disease. It was evidenced that young and adult groups are different kind
      of patients, the former showing much more cerebral veins stenosis and blocked
      flow in internal jugular veins and vertebral veins than the latter. Duration of
      disease could explain such differences: the higher the diseases duration, the
      higher the degree of vascular alterations and, therefore, the disability degree.
      This could be due to the complex venous hemodynamic impairments induced by
      alterations in vascular walls: the blocked or difficult blood flow through
      stenosis could increase the hydrostatic pressure in the skull and this could
      induce damages to cerebral cells leading to the genesis of more advanced
      morphological abnormalities. Furthermore, the vessels' alterations could impair
      venous endothelial functions which could turn in a possible alteration of the
      controls of cerebral vein return which could worsen the cerebral vascular
      outflow. It may be possible that early clinical, pharmacological and/or invasive
      vascular interventions could exert a possible role in the natural history of
      multiple sclerosis. Nevertheless, further trials are needed in order to confirm
      such considerations.

PMID- 24274910
TI  - APIC Strategic Partner Program.

PMID- 24274911
TI  - National Healthcare Safety Network (NHSN) report, data summary for 2012, Device
      associated module.

PMID- 24274912
TI  - Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal
      colonization with nonabsorbable oral antibiotic treatment: A prospective
      controlled trial.
AB  - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In
      attempt to eradicate CRE colonization, we conducted a semirandomized,
      prospective, controlled trial using oral nonabsorbable antibiotics. METHODS:
      Consecutive hospitalized CRE carriers were studied. Patients whose rectal
      isolates were gentamicin sensitive but colistin resistant were treated with
      gentamicin. Patients whose isolates were colistin sensitive but gentamicin
      resistant were treated with colistin. Patients whose isolates were sensitive to
      both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin,
      colistin, or both. Patients whose isolates were resistant to both drugs, and
      those who did not consent, were followed for spontaneous eradication. RESULTS:
      One hundred fifty-two patients were included; 102 were followed for spontaneous
      eradication for a median duration of 140 days (controls), and 50 received 1 of
      the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a
      median duration of 33 days. Eradication rates in the 3 treatment groups were 42%,
      50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous
      eradication rate in the control group (P < .001, P < .001, and P = .004,
      respectively) with no difference between the regimens. No significant adverse
      effects were observed. CONCLUSION: Oral antibiotic treatment with nonabsorbable
      drugs to which CRE is susceptible appears to be an effective and safe for
      eradication of CRE colonization and, thereby, may reduce patient-to-patient
      transmission and incidence of clinical infection with this difficult-to-treat
      organism.

PMID- 24274913
TI  - New sensitive high-performance liquid chromatography-tandem mass spectrometry
      method for the detection of horse and pork in halal beef.
AB  - The accidental or fraudulent blending of meat from different species is a highly
      relevant aspect for food product quality control, especially for consumers with
      ethical concerns against species, such as horse or pork. In this study, we
      present a sensitive mass spectrometrical approach for the detection of trace
      contaminations of horse meat and pork and demonstrate the specificity of the
      identified biomarker peptides against chicken, lamb, and beef. Biomarker peptides
      were identified by a shotgun proteomic approach using tryptic digests of protein
      extracts and were verified by the analysis of 21 different meat samples from the
      5 species included in this study. For the most sensitive peptides, a multiple
      reaction monitoring (MRM) method was developed that allows for the detection of
      0.55% horse or pork in a beef matrix. To enhance sensitivity, we applied MRM(3)
      experiments and were able to detect down to 0.13% pork contamination in beef. To
      the best of our knowledge, we present here the first rapid and sensitive mass
      spectrometrical method for the detection of horse and pork by use of MRM and
      MRM(3). 

PMID- 24274914
TI  - Examining the scope of questionable diagnostic reliability in Sexually Violent
      Predator (SVP) evaluations.
AB  - Research has suggested questionable reliability of diagnosing mental abnormality
      during Sexually Violent Predator (SVP) evaluations, despite this being a
      necessary requirement for SVP commitment. Findings have been inconsistent across
      studies, and little is known about the extent of such trends across diagnoses and
      clinicians. The current study includes data from 375 sex offenders referred for
      evaluation for SVP commitment in New Jersey. Clinicians (n = 128) rendered a
      variety of diagnoses, most commonly Pedophilia. Results suggested questionable
      agreement across paraphilic and non-paraphilic diagnoses, although agreement was
      fair for diagnoses of Pedophilia. Further analyses of cases (n = 49) involving
      clinicians receiving a large number of referrals (n = 14) were generally
      consistent with these findings, with no outlier effect apparent. Findings suggest
      questionable diagnostic reliability to be a widespread issue in SVP evaluations,
      present across a variety of diagnoses and across the general body of clinicians
      involved in evaluations.

PMID- 24274915
TI  - A model to systematically employ professional judgment in the Bayesian Decision
      Analysis for a semiconductor industry exposure assessment.
AB  - Bayesian Decision Analysis (BDA) uses Bayesian statistics to integrate multiple
      types of exposure information and classify exposures within the exposure rating
      categorization scheme promoted in American Industrial Hygiene Association (AIHA)
      publications. Prior distributions for BDA may be developed from existing
      monitoring data, mathematical models, or professional judgment. Professional
      judgments may misclassify exposures. We suggest that a structured qualitative
      risk assessment (QLRA) method can provide consistency and transparency in
      professional judgments. In this analysis, we use a structured QLRA method to
      define prior distributions (priors) for BDA. We applied this approach at three
      semiconductor facilities in South Korea, and present an evaluation of the
      performance of structured QLRA for determination of priors, and an evaluation of
      occupational exposures using BDA. Specifically, the structured QLRA was applied
      to chemical agents in similar exposure groups to identify provisional risk
      ratings. Standard priors were developed for each risk rating before review of
      historical monitoring data. Newly collected monitoring data were used to update
      priors informed by QLRA or historical monitoring data, and determine the
      posterior distribution. Exposure ratings were defined by the rating category with
      the highest probability--i.e., the most likely. We found the most likely exposure
      rating in the QLRA-informed priors to be consistent with historical and newly
      collected monitoring data, and the posterior exposure ratings developed with QLRA
      informed priors to be equal to or greater than those developed with data-informed
      priors in 94% of comparisons. Overall, exposures at these facilities are
      consistent with well-controlled work environments. That is, the 95th percentile
      of exposure distributions are <=50% of the occupational exposure limit (OEL) for
      all chemical-SEG combinations evaluated; and are <=10% of the limit for 94% of
      chemical-SEG combinations evaluated.

PMID- 24274916
TI  - Healthier choices in an Australian health service: a pre-post audit of an
      intervention to improve the nutritional value of foods and drinks in vending
      machines and food outlets.
AB  - BACKGROUND: Vending machines and shops located within health care facilities are
      a source of food and drinks for staff, visitors and outpatients and they have the
      potential to promote healthy food and drink choices. This paper describes
      perceptions of parents and managers of health-service located food outlets
      towards the availability and labelling of healthier food options and the food and
      drinks offered for sale in health care facilities in Australia. It also describes
      the impact of an intervention to improve availability and labelling of healthier
      foods and drinks for sale. METHODS: Parents (n = 168) and food outlet managers (n
      = 17) were surveyed. Food and drinks for sale in health-service operated food
      outlets (n = 5) and vending machines (n = 90) in health care facilities in the
      Hunter New England region of NSW were audited pre (2007) and post (2010/11) the
      introduction of policy and associated support to increase the availability of
      healthier choices. A traffic light system was used to classify foods from least
      (red) to most healthy choices (green). RESULTS: Almost all (95%) parents and most
      (65%) food outlet managers thought food outlets on health service sites should
      have signs clearly showing healthy choices. Parents (90%) also thought all food
      outlets on health service sites should provide mostly healthy items compared to
      47% of managers. The proportion of healthier beverage slots in vending machines
      increased from 29% to 51% at follow-up and the proportion of machines that
      labelled healthier drinks increased from 0 to 26%. No outlets labelled healthier
      items at baseline compared to 4 out of 5 after the intervention. No changes were
      observed in the availability or labelling of healthier food in vending machines
      or the availability of healthier food or drinks in food outlets. CONCLUSIONS:
      Baseline availability and labelling of healthier food and beverage choices for
      sale in health care facilities was poor in spite of the support of parents and
      outlet managers for such initiatives. The intervention encouraged improvements in
      the availability and labelling of healthier drinks but not foods in vending
      machines.

PMID- 24274917
TI  - The multifaceted nature of access to compounded progesterone: a cross-sectional
      study from Australia.
AB  - OBJECTIVE: To explore the influences on accessibility of compounded progesterone
      therapy for Australian women. STUDY DESIGN: A cross-sectional survey of a
      stratified sample of Australian women who use progesterone only products using
      the 'Perspectives on Progesterone' questionnaire. MAIN OUTCOME MEASURES:
      Principle components analysis (PCA) to determine components of access to
      progesterone treatment and multi-way analysis of variance to compare groups.
      RESULTS: Women using compounded progesterone were likely to have made at least
      one lifestyle adaptation (73%), and to have tried and stopped using at least one
      complementary and alternative medicine therapy (63%) or conventional hormone
      therapy (41%). PCA revealed six components of access to progesterone treatment:
      affordable, values natural treatments and is concerned about other treatments,
      conventionally available, perceived knowledge, values information gathered from a
      variety of sources, and rural & disadvantaged. The multifaceted nature of
      progesterone use illustrates that there are multiple aspects to use of non
      conventional medicines. Women looking for non-conventional treatment are neither
      stupid nor uninformed, their understandings, based on experience and research,
      need to be addressed by health professionals while assessing their condition
      prior to discussing the risks and benefits of non-conventional medicines.
      CONCLUSION: Access to compounded progesterone is multifaceted, and many of the
      women who use it have tried other treatments first. Despite the clinical
      ambivalence towards progesterone as an alternative for women who may have tried
      and rejected other treatments, including conventional hormone therapy, the women
      described in this paper are using it.

PMID- 24274918
TI  - Lesions of the avian pancreas.
AB  - Although not well described, occasional reports of avian exocrine and endocrine
      pancreatic disease are available. This article describes the lesions associated
      with common diseases of the avian pancreas reported in the literature and/or seen
      by the authors. 

PMID- 24274919
TI  - Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical
      aspects.
AB  - This article describes the anatomy of the avian hypothalamic/pituitary axis, the
      hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the
      hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

PMID- 24274920
TI  - Use of GnRH-agonists for medical management of reproductive disorders in birds.
AB  - Pet birds suffer from a wide range of reproductive conditions and diseases.
      Chronic egg laying, egg binding, and excessive reproductive activities are common
      problems. Veterinarians may prescribe behavior modification, changes in captive
      care, and medical therapy to curb these behaviors. Surgical removal of the
      oviduct is effective at stopping egg production; however, it is a specialized
      surgery that carries surgical and anesthetic-related risks. The inability to
      surgically remove the ovary in birds may result in persistent ovarian activity
      and secondary complications. Therefore, hormone therapy as an adjunct or main
      therapeutic approach, using sustained-release GnRH agonists, shows promise in pet
      birds.

PMID- 24274921
TI  - Nonsurgical management of hyperadrenocorticism in ferrets.
AB  - Several medical therapeutic options are available for the management of the
      clinical signs of adrenal disease in ferrets. Many of these medical modalities
      seem to be well tolerated and are a suitable alternative to adrenalectomy,
      especially for ferrets that are not surgical candidates. However, drugs that are
      currently available only manage the symptoms and do not provide a cure for the
      diseased adrenal gland, which may continue to enlarge. The medical management of
      urinary obstruction caused by prostatic enlargement and nonregenerative anemia
      caused by hyperestrogenism are also discussed in this article.

PMID- 24274922
TI  - Thyroid diseases in rodent species.
AB  - There are an abundance of studies of thyroid disease in rodents in a laboratory
      setting; however, research is limited in pet rodent populations. Validated
      reference intervals for thyroid testing are scarce, making interpretation of
      blood work difficult. Hyperthyroidism and hypothyroidism have been reported in
      multiple rodent species, with the most data available for guinea pigs. Thyroid
      neoplasia has been reported in the most common rodent species, although often as
      an incidental finding at necropsy. Further research is needed to determine
      frequencies of disease, methods of diagnosing, and treatment options with the
      best efficacy. 

PMID- 24274923
TI  - Ovarian cystic disease in guinea pigs.
AB  - Ovarian cysts are nonfunctional, fluid-filled cysts that develop spontaneously
      near the ovaries throughout the female guinea pig's reproductive cycle, reducing
      fertility in females older than 15 months and causing potentially serious uterine
      disorders. Permanent treatment requires ovariohysterectomy or ovariectomy. This
      article reviews the clinical signs, diagnosis, histopathology, treatment
      (including hormonal therapies), surgery, and postoperative care.

PMID- 24274924
TI  - Feather loss and feather destructive behavior in pet birds.
AB  - Feather loss in psittacine birds is a common and frustrating clinical
      presentation. Causes include medical and nonmedical causes of feather loss with
      and without overt feather destructive behavior. Underlying causes include
      inappropriate husbandry and housing; parasitic, viral and bacterial infections;
      metabolic and allergic diseases; and behavioral disorders. Prior to a diagnosis
      of a behavioral disorder, medical causes of feather loss must be excluded through
      a complete medical work-up including history, physical examination, and
      diagnostic testing. This article focuses on common medical and nonmedical causes
      of feather loss and feather destructive behavior and approaches to diagnosis and
      treatment.

PMID- 24274925
TI  - Topics in endocrinology. Preface.

PMID- 24274926
TI  - Studies on difficult intramolecular hydroaminations in the context of four
      syntheses of alkaloid natural products.
AB  - Examples of intramolecular alkene hydroaminations forming six-membered ring
      systems are rare, especially for systems in which the double bond is
      disubstituted. Such cyclizations have important synthetic relevance. Herein we
      report a systematic study of these cyclizations using recently developed Cope
      type hydroamination methodologies. Difficult intramolecular alkene
      hydroaminations were used as key steps in syntheses of 2-epi-pumiliotoxin C,
      coniine, N-norreticuline and desbromoarborescidine A. This effort required the
      development of optimized hydroamination conditions to improve the efficiency of
      the cyclizations. Collectively, our results show that Cope-type cyclizations can
      be achieved on a variety of challenging substrates and proceed under similar
      conditions for both N-H and N-substituted hydroxylamines. 

PMID- 24274927
TI  - Immunohistochemical diagnosis of tenacibaculosis in paraffin-embedded tissues of
      Senegalese sole Solea senegalensis Kaup, 1858.
AB  - A sensitive and specific immunohistochemical technique was developed to improve
      the diagnosis of tenacibaculosis and to better understand its pathogenesis.
      Senegalese sole Solea senegalensis Kaup, 1858 were inoculated subcutaneously with
      a bacterial suspension of Tenacibaculum maritimum, and samples were taken at
      different hours post-inoculation. Sections from different organs were used as
      positive controls. In addition, a total of 128 field samples from different
      organs collected from tenacibaculosis outbreaks were used. Tenacibaculum
      maritimum antigens were detected in several organs of experimentally infected
      Senegalese sole and in at least one of the tissues from fish suffering from
      natural tenacibaculosis previously confirmed by culture and PCR-based methods. In
      fish collected during outbreaks, a strong positive reaction was detected in
      ulcerative skin areas. Moreover, bacterial antigen was identified inside scale
      pockets and in sites of the skin with mild lesion. In kidney and spleen, evident
      immunostaining of bacterial antigen was detected in both naturally and
      experimentally infected fish. Besides, the presence of T. maritimum in the
      intestinal tract without associated histological changes suggests that this organ
      may act as a reservoir for T. maritimum. The results of this study confirm the
      usefulness of IHC for the diagnosis of tenacibaculosis in paraffin-embedded
      tissues. 

PMID- 24274928
TI  - The utility of using fiberoptic rhinoscopy in the diagnosis of nasal polyps.
AB  - BACKGROUND: Symtomatology of nasal polyps (NP) is relatively non-specific and
      other nasal conditions that cause nasal may be mistaken for NP. The purpose of
      this study was to evaluate the accuracy otoscopic (OT) examination in detecting
      presence of NP by using fiberoptic rhinoscopy (FR) as the gold standard to
      confirm diagnosis of NP. METHODS: Charts from a single allergy clinic were
      reviewed for any patient having NP diagnosed by FR. Data collected included
      gender, age, allergy skin test results, and presence of asthma, aspirin allergy,
      previous nasal surgeries, intranasal corticosteroid use and leukotriene receptor
      antagonist use. RESULTS: The OT examination had 44% sensitivity. In this study,
      more than half (56%) of patients with NP would have had their NP missed if FR had
      not been performed in addition to the OT examination. CONCLUSIONS: The standard
      physical examination procedure is often not sufficient to confirm a diagnosis of
      NP. FR should be considered in the investigation of patients with rhinitis
      symptoms.

PMID- 24274929
TI  - Intracranial hemorrhage in infants with cephalohematoma.
AB  - BACKGROUND: Intracranial hemorrhage (ICH) is a rare birth injury in term infants.
      Newborn infants with cephalohematoma (CH) associated with ICH, however, have
      frequently been found incidentally at Kyungpook National University Hospital;
      many of them had no neurological symptoms. The aim of this study was to evaluate
      the clinical manifestations of ICH in newborn infants with CH. METHODS: Newborn
      infants with CH in the neonatal intensive care unit were retrospectively
      evaluated. During period I (5 years), neuroimaging (brain computed tomography and
      magnetic resonance imaging) was performed when intracranial abnormalities were
      suspected. During period II (36 months) neuroimaging was performed when CH > 5 cm
      in diameter was present. RESULTS: During period I, seven out of 19 infants who
      underwent neuroimaging had ICH (36.8%) including two epidural hemorrhages (EDH).
      During period II, 18 out of 27 infants who underwent neuroimaging had ICH
      (66.7%), including two EDH. There was no significant difference in the clinical
      manifestations between infants with and without ICH. In 10 cases of CH
      accompanied with a linear skull fracture, nine had ICH, including all cases of
      ICH that needed intervention. CONCLUSIONS: The association of ICH appears to be
      common in newborn infants with CH; particularly in infants with CH accompanied
      with a skull fracture, the rate of ICH was very high, and all cases of EDH
      requiring intervention were associated with skull fracture. Therefore, evaluation
      of accompanying skull fracture should be required in infants with CH, and, in
      cases of skull fracture, neuroimaging should be considered.

PMID- 24274930
TI  - Is there evidence for correct diagnosis in cystic fibrosis registries?
AB  - BACKGROUND: Cystic fibrosis (CF) spans a wide spectrum. Therefore, benchmarking
      between registries implies comparing similar cohorts. OBJECTIVE AND METHODS:
      Explore patient characteristics in Belgian (B), French (F), German (G) and Dutch
      (NL) registries (total N=13,122) and determine whether they fulfill predefined
      diagnostic criteria. RESULTS: Using as case definition sweat chloride >60mmol/L
      or 2 CFTR mutations identified, CF diagnosis was not documented in 2.8, 5.7, 6.5
      and 21.6% of subjects in the F, B, NL, and G registries. Restricting CFTR
      mutation interpretation to 124 CF causing mutations in CFTR2, these numbers rose
      to 10.5, 10.4, 14.5 and 24.3% respectively. Excluding these subjects impacted on
      outcomes. The impact differed between countries; the largest changes seen were a
      decrease in % adults from 51.9 to 47.8% in G, a decrease in % pancreas
      sufficiency from 17.0 to 13.0 in F, an increase in % homozygous for F508del from
      55.3 to 63.7 in NL and a decrease of % with sweat chloride <=60mmol/L from 8.4 to
      1.1 in B. CONCLUSION: CF diagnosis is not documented in 10 to 24% of patients
      included in CF registries. Excluding these patients for analyses leads to
      significant changes in outcomes.

PMID- 24274931
TI  - Deciphering the human brain proteome: characterization of the anterior temporal
      lobe and corpus callosum as part of the Chromosome 15-centric Human Proteome
      Project.
AB  - Defining the proteomes encoded by each chromosome and characterizing proteins
      related to human illnesses are among the goals of the Chromosome-centric Human
      Proteome Project (C-HPP) and the Biology and Disease-driven HPP. Following these
      objectives, we investigated the proteomes of the human anterior temporal lobe
      (ATL) and corpus callosum (CC) collected post-mortem from eight subjects. Using a
      label-free GeLC-MS/MS approach, we identified 2454 proteins in the ATL and 1887
      in the CC through roughly 7500 and 5500 peptides, respectively. Considering that
      the ATL is a gray-matter region while the CC is a white-matter region, they
      presented proteomes specific to their functions. Besides, 38 proteins were found
      to be differentially expressed between the two regions. Furthermore, the proteome
      data sets were classified according to their chromosomal origin, and five
      proteins were evidenced at the MS level for the first time. We identified 70
      proteins of the chromosome 15 - one of them for the first time by MS - which were
      submitted to an in silico pathway analysis. These revealed branch point proteins
      associated with Prader-Willi and Angelman syndromes and dyskeratosis congenita,
      which are chromosome-15-associated diseases. Data presented here can be a useful
      for brain disorder studies as well as for contributing to the C-HPP initiative.
      Our data are publicly available as resource data to C-HPP participant groups at
      http://yoda.iq.ufrj.br/Daniel/chpp2013. Additionally, the mass spectrometry
      proteomics data have been deposited to the ProteomeXchange with identifier
      PXD000547 for the corpus callosum and PXD000548 for the anterior temporal lobe.

PMID- 24274932
TI  - Harlequin ichthyosis: neonatal management and identification of a new ABCA12
      mutation.
AB  - A case of harlequin ichthyosis with compound heterozygous mutations in ABCA12 was
      successfully managed with intensive neonatal care and endotracheal intubation and
      without oral retinoids. The individual's appearance improved dramatically during
      hospitalization and at discharge resembled congenital ichthyosiform erythroderma.

PMID- 24274933
TI  - Letter to the Editor: Response to 'Augmenting cognitive behavior therapy for post
      traumatic stress disorder with emotion tolerance training'.

PMID- 24274934
TI  - Knowledge of stroke symptoms and treatment among community residents in Western
      Urban China.
AB  - BACKGROUND: Prehospital delay is still now the main barrier in receiving acute
      stroke therapy. Increase public awareness of stroke warning signs may help to
      activate emergency medical services and reduce prehospital delay. Our objectives
      were to survey the recognition of stroke warning signs among residents of Yuzhong
      District in Chongqing, China, and determine the proportion of these residents who
      would make an emergency call (120, in China) if suddenly faced with unexpected
      stroke warning signs and analyze the relationship between recognition of stroke
      warning signs and the response of calling for emergency assistance. METHODS: In
      2011, a population-based face-to-face interview survey using a multistage
      sampling method was conducted in Yuzhong District, Chongqing. We assessed
      residents' recognition of stroke warning signs and the proportion of those who
      would call the emergency number, 120, if suddenly encountering unexpected stroke
      warning signs. The association between the knowledge of stroke warning signs and
      activation of 120 was examined. RESULTS: A total of 1101 participants completed
      the questionnaire. Only 15.6% of respondents knew all 5 stroke warning signs;
      17.6% reported that they would call 120 for all 5 stroke warning signs.
      Recognition of stroke warning signs was associated with the response of calling
      120 (odds ratios, 1.92-3.34). Even among those who knew all 5 warning signs of
      stroke, only 35.5% (95% confidence interval, 28.3-42.6) would call 120 for all 5
      signs. CONCLUSIONS: Residents of the examined district in Chongqing exhibited low
      recognition of stroke warning signs and low awareness of appropriate emergency
      responses to stroke-related symptoms.

PMID- 24274935
TI  - Adenosine diphosphate-induced platelet aggregation might contribute to poor
      outcomes in atrial fibrillation-related ischemic stroke.
AB  - Systemic atherosclerosis is involved in ischemic damages and cardioembolism after
      atrial fibrillation (AF)-related ischemic stroke (IS). Platelet activation is a
      critical factor in systemic atherosclerosis; however, there is little information
      regarding the role of platelet activation on the outcome of AF-related IS. We
      investigated the relationship between adenosine diphosphate (ADP)-induced
      platelet aggregation and the long-term outcomes of AF-related IS. We studied 249
      patients who were exclusively treated with anticoagulation therapy after they had
      experienced AF-related IS. We evaluated their platelet function 5 days after
      admission to the hospital by using an optic platelet aggregometer test. We also
      assessed the prognoses of patients 90 days after the AF-related IS. Our results
      showed that ADP-induced platelet aggregation was positively correlated with
      CHA2DS2-VASc scores (r = .285, P < .01). Totally, 107 (43.0%) patients had a poor
      outcome at 90 days after IS. Univariate analysis showed that the following
      factors significantly contribute to a poor outcome: older age (odds ratio [OR] =
      1.07, confidence interval [CI] 1.04-1.10, P < .01), a history of stroke (OR =
      3.24, CI 1.61-6.53, P < .01), high scores on the National Institutes of Health
      Stroke Scale (NIHSS; OR = 1.25, CI 1.18-1.32, P < .01), increased white blood
      cell counts (OR = 1.12, CI 1.02-1.24, P < .01), high CHA2DS2-VASc scores (>=5, OR
      = 7.31, CI 3.36-15.93, P = .025), and the highest tertile of ADP-induced platelet
      aggregation (>=72%, OR = 3.17, CI 1.67-5.99, P < .01). Of these factors, high
      NIHSS scores (OR = 1.27, CI 1.20-1.36, P < .01), high CHA2DS2-VASc scores (OR =
      4.69, CI 1.21-18.14, P = .03), and the highest tertile of ADP-induced platelet
      aggregation (OR = 2.49, CI 1.17-5.27, P = .02) were independently associated with
      a poor outcome at 90 days after IS. Therefore, our results suggest that platelet
      activation might affect the outcome of AF-related IS.

PMID- 24274936
TI  - Macrophage migration inhibitory factor regulates AKT signaling in hypoxic culture
      to modulate senescence of human mesenchymal stem cells.
AB  - Hypoxic culture has been shown to delay premature senescence occurring during in
      vitro culture. Human mesenchymal stem cells (hMSCs) cultured under hypoxia have
      been reported to maintain their stemness properties and delay senescence compared
      to the cells cultured under normoxia. However, the molecular mechanism by which
      hypoxia regulates premature senescence has not been fully revealed. In this
      study, hMSCs were cultured under the conditions of 21% (normoxia) and 1% O2
      (hypoxia) tension and analyzed for cell growth, expression of MSC surface
      markers, multilineage differentiation, and cellular senescence. Our results
      showed that more cells retained MSC surface markers in hypoxic culture than those
      in normoxic culture, and hypoxia was able to enhance multilineage differentiation
      of hMSCs. The hypoxic condition also delayed cellular senescence of hMSCs,
      increased activation of AKT signaling, and upregulated both intra- and
      extracellular levels of macrophage migration inhibitory factor (MIF) compared to
      the normoxic condition. Inhibition of AKT activity in hypoxic culture increased
      the number of cells with positive staining for senescence-associated beta
      galactosidase activity, upregulated expression levels of senescence-associated
      markers p16 and p21 mRNA transcripts, and decreased expression levels of potency
      associated markers, including NANOG, OCT3/4, and SOX2. On the other hand,
      upregulated intra- and extracellular levels of MIF by stable MIF overexpression
      in normoxic culture increased the activation of AKT while decreasing mRNA
      expression of senescence-associated markers and increasing expression of potency
      associated markers. Taken together, our findings suggest that hMSCs in hypoxic
      culture produce endogenous MIF to activate AKT signaling to delay the progression
      of cellular senescence. 

PMID- 24274937
TI  - Cervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16
      prevalence and vaccination impact.
AB  - INTRODUCTION: The etiology of cervical intraepithelial neoplasia grade 2 or worse
      (CIN2+) can influence the efficacy of Public Health preventive strategies. This
      study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in
      CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of
      bivalent vaccination, and the distribution of HPV 16 in squamous lesions.
      MATERIAL AND METHODS: Ninety-four histologically confirmed cases of CIN2+ (2009
      2010) were retrospectively studied: 23 CIN2, 58 CIN3- squamous carcinoma in situ
      (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical
      cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim,
      Germany) was performed on the cervical specimens. Bivalent vaccination impact was
      calculated, based on regional vaccination coverage data, local HR-HPV prevalence,
      and reported efficacy (direct and cross-protection) of the vaccine. RESULTS: HR
      HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8-58.2%)
      and HPV 31 (9.3%-12.1%), considering single infections or single-multiple
      infections, respectively (hierarchical attribution). In squamous lesions, HPV 16
      prevalence in women younger than 45 years of age increased in severe lesions
      (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine
      could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or
      by 62.7% (direct and cross-protection). CONCLUSION: HPV vaccination could have a
      great impact in women younger than 45 years of age due to the high prevalence of
      HPV 16 in their lesions.

PMID- 24274938
TI  - Surfactant-assisted size control of hydroxyapatite nanorods for bone tissue
      engineering.
AB  - This study presents the physicochemical characterization of the pluronic
      surfactant-assisted size control of hydroxyapatite (HAp) nanorods for bone tissue
      engineering (BTE). Rod-shaped HAp nanoparticles were synthesized via a simple
      route by hydrothermal treatment and with the assistance of the triblock co
      polymer PEO20-PPO70-PEO20 (P123). The films of poly (d, l) lactic acid (PDLLA)
      were prepared as a substrate to spread synthesized HAp nanorods. Powder X-ray
      diffraction (XRD), field electron scanning microscopy, Fourier transform infrared
      spectroscopy, nitrogen adsorption isotherms, and energy-dispersive X-ray
      spectroscopy were used to characterize the structure and composition of the HAp
      samples. Results showed that regular rod-shaped HAp nanoparticles (with a mean
      length of 120 nm and a mean width of 28 nm) were successfully produced. Moreover,
      synthesized HAp nanorods revealed the rapid formation of bone-like apatite with a
      distinctive morphology, similar to flower-like apatite; the formation was
      observed as early as 7 days after incubation in stimulated body fluids. This
      study is a positive addition to the ongoing research on the preparation of HAp
      nanostructures toward the development of biocompatible composite scaffolds for
      BTE applications.

PMID- 24274939
TI  - Interfacing of dextran coated ferrite nanomaterials with cellular system and
      delayed hypersensitivity on Guinea pigs.
AB  - The study focused on the interfacing of dextran coated ferrite nanomaterials
      (DFNM) with the cellular system and delayed hypersensitivity on Guinea pigs. In
      vitro study investigated the cytotoxic potential of DFNM on L929 cells, effect on
      antioxidant enzymes and Lipid peroxides (LPO) production on rat brain
      homogenates. DFNM was also repeatedly exposed topically to Guinea pigs for the
      evidence of skin sensitization and toxicity at the molecular level. Biochemical
      and hematological parameters were estimated. Liver and brain of Guinea pigs were
      homogenized and evaluated for the induction of LPO, glutathione (GSH),
      glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase
      (SOD) and 8-hydroxyl-2-deoxyguanosine (8-OHdG). The results of the study
      demonstrated that there was no significant alternation in the level of
      antioxidant defense enzymes, LPO, hematological, biochemical or oxidative stress
      related DNA damage. Hence, it can be concluded that the synthesized DFNM was non
      skin irritant or non-toxic at the molecular level under the laboratory
      conditions. 

PMID- 24274940
TI  - [Bladder augmentation in childhood and adolescence: beware of risk of cancer on
      adult patients].

PMID- 24274941
TI  - [PSA interest and prostatitis: literature review].
AB  - Prostatitis is easily diagnosed but sometimes associated with PSA measurement. An
      increased PSA in an asymptomatic patient may be associated with antibiotic use to
      eliminate the inflammatory part and to confirm prostate biopsy. It seems
      interesting to confirm or infirm these attitudes with a systematic review of the
      literature METHOD: We performed a literature review using the words
      [prostatitis], [acute prostatitis], [prostate specific antigen], [PSA], in the
      MEDLINE, Pubmed and AMBASE database searching for articles in French or English
      published in the past 20 years. RESULTS: PSA is not always increased during an
      acute prostatitis episode. An increased PSA in an asymptomatic man does not seem
      to be systematically correlated to prostate inflammation. Analyzing the studies,
      it seems inaccurate to measure PSA value during a febrile urinary infection
      episode in men. Systematic use of antibiotic to decrease PSA and not performing
      prostate biopsy is not relevant and may induce resistance to antibiotic and
      doesn't induce a reduction risk of having prostate biopsy. CONCLUSION: PSA is
      unnecessary in case of febrile urinary tract infection in men.

PMID- 24274942
TI  - [Prognostic factors of upper tract urothelial carcinoma].
AB  - INTRODUCTION: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease.
      Thus, little evidence-based data are available to guide clinical decision-making.
      The aim of the study was to provide an overview of the currently available
      prognostic factors for UTUC. MATERIAL AND METHODS: A systematic literature search
      was conducted using the PubMed databases to identify original articles regarding
      prognostic factors in patients with UTUC. RESULTS: We divided the prognostic
      factors for UTUC in four different categories: clinical factors, preoperative
      characteristics, intraoperative/surgical factors and postoperative/pathologic
      factors. Prognostic factors described in order of importance are: tumor stage and
      grade, lymph node involvement, a concomitant cis, age at the diagnostic,
      lymphovascular invasion, tumor architecture and necrosis, tumor location and
      multifocality, gender. The impact of obesity, smoking and other comorbidities
      (ECOG, ASA) on outcomes has been recently reported but needs to be validated. The
      endoscopic approach of distal ureter management during radical nephroureterectomy
      has been shown to be at higher risk of bladder recurrence. CONCLUSION: The
      incorporation of such prognosticators into clinical prediction models might help
      to guide decision-making with regard to timing of surveillance, type of
      treatment, performance of lymphadenectomy, and consideration of neoadjuvant or
      adjuvant systemic therapies.

PMID- 24274943
TI  - [Management of adult's renal and ureteral stones. Update of the Lithiasis
      Committee of the French Association of Urology (CLAFU). General considerations].
AB  - The Lithiasis Committee of the French Association of Urology (CLAFU) aimed to
      update the current knowledge about urolithiasis. This update will be divided into
      four parts: 1) general considerations; 2) the management of ureteral stones; 3)
      the management of kidney stones; 4) metabolic assessment and medical treatment of
      urolithiasis. Recent technicals advances helped the urologists to improve stones
      management: new extracorporeal shockwave lithotripsy (ESWL) devices, new flexible
      ureterorenoscopes, development of laser fragmentation. ESWL, semi-rigid and
      flexible ureteroscopy and the percutaneous nephrolithotomy (PCNL) remain
      currently the main therapeutic options. The first part of this update deals with
      the description and classification of stones, preoperative assessment, post
      operative management and clinical follow-up. Main criteria of therapeutic choices
      are stone location, stone composition and stone size. Stone composition is
      assessed with infrared spectrophotometry analysis and its hardness is correlated
      with U.H. density on CT scan assessment. Preoperative assessment consists in
      urinary cytobacteriological examine, urinary PH, blood creatininemia, hemostasis.
      Low-dose CT scan is recommended before urological treatment. The result of the
      treatment must be done 1 or 3 months later with plain abdominal film and
      ultrasonography. Medical management of urolithiasis will be based on stone
      composition, metabolic and nutritional evaluation. Treatment success is definited
      by absence of residual fragments. Annual follow-up is recommended and based
      either on plain abdominal film and ultrasonography or low-dose CT scan.

PMID- 24274944
TI  - [Emergency nephrectomies: retrospective monocentric study, about eight cases].
AB  - OBJECTIVE: Emergency nephrectomies are rare because of the improvement of the
      management of urinary tract infections and the development of radio-embolization.
      Few series of patients have been reported. The objective of our study is to
      assess the indication, the morbi-mortality and the outcome of the emergency
      nephrectomy performed in our hospital. PATIENTS: Between January 2011 and
      November 2012, eight patients underwent an emergency nephrectomy at the
      University Hospital Center of Caen. The present review reports the
      characteristics of this emergency nephrectomy and their morbi-mortality. RESULTS:
      Six women and two men were analyzed retrospectively between January 2011 and
      November 2012. All patients except one needed intensive care for a multiple-organ
      failure. All these eight emergency nephrectomies concerned a native kidney with a
      surgical approach as a lombotomy or subcostal laparotomy. Both patients survived.
      One patient need a renal dialysis support. CONCLUSION: Emergency nephrectomy are
      rare. Uncontrolled urinary sepsis represents the main indication. Identifying the
      population at risk of evolution to the toxic shock is indispensable for a better
      and faster care and to reduce the mortality bound to the sepsis.

PMID- 24274945
TI  - [Screening of prostate cancer seen by general practitioners].
AB  - INTRODUCTION: The screening of prostate cancer was recently the subject of
      international studies and debates in France. We decided to study the vision of
      the screening, in particular by the PSA, which have the general practitioners.
      METHODS: We sent a questionnaire to 456 general practitioners of Oise (French
      department) to be returned in an anonymous way on the prostate cancer, PSA, the
      economic impact of the PSA and we asked whether the doctors realized the
      screening or not, if they were favorable to it and for which reasons. RESULTS: We
      received 38% of answers. Eighty-one percent of the general practitioners
      considered that prostate cancer is frequent, 72% that it evolved slowly and 55%
      that it affected old men. For 79% of the general practitioners, the patients were
      asking for a screening by PSA. Eighty-eight percent thought that they had to be
      in front line of the screening, 58% that the functional consequences of the
      screening were satisfactory. Fifty-seven percent of the general practitioners
      realized the screening in a systematic way and 88% were favorable to it.
      CONCLUSION: The general practitioners of Oise remained favorable for the greater
      part to the screening of prostate cancer and the patients applicants in spite of
      various debates.

PMID- 24274946
TI  - [Preoperative endorectal MRI in prostate cancer: a monocentric retrospective
      cohort].
AB  - INTRODUCTION: The aim of the study was to assess the added value of a prostatic
      MRI performed in a non-expert center before radical prostatectomy for prostate
      cancer. PATIENTS AND METHODS: All patients considered for a radical prostatectomy
      for a clinically localised prostate cancer in our institution between June 2006
      and April 2011 were analysed. They underwent a systematic endorectal 1.5 T MRI
      [eMRI] (T2 and diffusion-weighted imaging). The procedure was performed at least
      8 weeks after transrectal ultrasound guided prostate biopsies. They were analyzed
      by a single experimented genitourinary radiologist. The preoperative
      characteristics and biopsy data were collected, as the eMRI interpretation using
      a systematic scale. Correlation between eMRI and final histopathology has been
      analyzed (standardized pathological report using the Stanford procedure). We
      considered the following points: extracapsular extension, seminal vesicle
      invasion and cancer localisation. Cancer localization was analyzed both by halves
      (left/right) and on sextant-basis (base, middle, apex, left and right
      respectively). For each data, sensitivity, specificity, positive (PPV) and
      negative predictive value (NPV) were calculated. Finally, we compared the results
      with those from the Partin's table and the Kattan's nomogram for T stage.
      RESULTS: Two hundred and fifteen patients underwent a radical prostatectomy,
      having a mean age of 63 +/- 6 years, a mean PSA: 7.8 +/- 3.8 ng/mL. One hundred
      and fifty-nine patients had organ confined disease. Fifty-six had pT3 disease (50
      pT3a and 6 pT3b). Sensibilities and specificities were the following: for
      extracapsular extension 26% and 96%; for seminal vesicle invasion 17% and 98%;
      for cancer localisation 64% and 74%; for prediction of left or right side 81% and
      48%. DISCUSSION: MRI showed equal performances compared to the Partin's table and
      the Kattan's nomogram for T stage. It showed lower performance compared to biopsy
      results for cancer localization (sensitivity 88%, specificity 70%). Literature
      provides wide ranges of results for eMRI. The results of this study were at the
      low limit of these ranges but reflect everyday practice. When performed, as it
      was in our study, eMRI did not seem to be accurate for staging. It had at best a
      very limited added value compared to the existing tools.

PMID- 24274947
TI  - [Inflatable penile prosthesis: satisfaction rate, result, prognostic factors.
      Prospective study on 50 primooperated patients in CHU of Nice between 2000 and
      2009].
AB  - OBJECTIVE: To evaluate satisfaction rates and results in patients with penile
      prosthesis (5 PP). MATERIALS AND METHODS: From January 2000 till 2009, 50
      patients with organic erectile dysfunction (ED) were implanted with hydraulics
      penile prosthesis by the same surgeon. Medical records were collected
      retrospectively. We analysed demographic characteristics, type of prosthesis
      used, per- and postoperative complications, prosthesis explantations and
      satisfaction rate measured by EDITS modified. RESULTS: Mean age of patients was
      60.2 +/- 8.46 years (35-75). Thirty implanted patients (60%) were diabetics. We
      used a peno-scrotal incision in all patients. Three types of prosthesis were
      used; AMS Ambicor, AMS 700, Titan OTR. A bi-compartment and three-compartment
      prosthesis were implanted respectively in 24 and 26 patients. The prosthesis was
      retrieved in two patients secondary to a mechanical failure, in three patients
      for prosthesis erosion, in two patients for prosthesis infection. In four out of
      the seven explanted patients, a second prosthesis was implanted. The EDITS
      questionnary was realized by telephonic interview in 47 patients after a mean
      follow-up of 45 months (5-114). The response rate was of 83%. The satisfaction
      rate was of 81%. CONCLUSION: In our series, the satisfaction rate was better for
      the three-compartment prosthesis. After 45 months of follow-up, 73% (31/42) of
      patients had a functional prosthesis. The non-satisfaction most frequently found
      were patients who have complications as sepsis; mechanical failure, and
      prosthesis erosion, and subjective feeling of penile length reduction.

PMID- 24274948
TI  - [Epidemiological and clinical aspects of visible urogenital malformations among
      adolescent's schoolboys at Cotonou].
AB  - AIMS: To detect systematically visible urogenital malformations (VUGM) in
      adolescents and describe their epidemiological and clinical aspects. PATIENTS AND
      METHODS: It was a cross sectional, descriptive and analytical study, conducted
      from February to August 2012. Upon 2724 adolescents from 10 to 19 years old, of
      the public secondary schools of Cotonou. Among the 26,594 registered pupils, 2724
      were included and examined after a randomized sampling of 30 clusters. RESULTS:
      The mean age of the pupils was of 15 +/- 2.30 years (11-19 years), with a peak at
      18 years. The prevalence of the VUGM was slightly higher (9.57%) in individuals
      those had parents with low socioeconomic level. The prevalence of the VUGM was
      high in Yoruba and related (P=0.02). It was stronger (9.84%) among subjects in
      puberty period's than in pre-puberty (6.69%) (P=0.03). From the 253 having VUGM,
      78 (30.83%) had 146 functional signs. It was indexed 266 affections and of
      malformatives associations in 21 pupils (8.30%). Varicocele was the most frequent
      (5.47%), followed by inguinal hernia (0.99%), hydrocele (0.88%), anomalies of
      testis migration (0.59%), cyst of spermatic cord (0.51%), insulated testicular
      hypotrophy (0.48%), micro-penile (0.33%), hypospadias (0.22%), penile curvature
      (0.22%) and epididymis cyst (0.07%). CONCLUSION: Among patients who had VUGM, the
      majority had at least a varicocele, which occupies so far the first place within
      these malformations at the adolescents in Cotonou.

PMID- 24274949
TI  - [Results of a survey on urologic activity in 1-day surgery in Midi-Pyrenees].
AB  - INTRODUCTION: One-day surgery is an exercise whose development has grown
      significantly over the last decade. This survey aims at reviewing the different
      aspects of this practice in urology, in the second largest region of France.
      MATERIALS AND METHODS: A cross-sectional study was conducted among the 57
      urologists working in the Midi-Pyrenees region. A computerized questionnaire was
      made available on Internet. The non-responder urologists received a reminder
      email every week. The questionnaire included 25 questions, divided into four
      subgroups. RESULTS: The response rate was 57.9% (33/57 urologists). Results
      showed that the 1-day surgery rate was 26.4%. It was higher in the private sector
      (33.07 +/- 17.16 vs. 20.42 +/- 13.54%, P=0.04). Surgeries were made mainly in non
      dedicated operating theaters (75.0%) and in the conventional list (71.8%). There
      was a written output protocol in 90.6% of cases (29 urologists), which was never
      given to the patient in 7.0% of cases (2 urologists) and never sent to the family
      doctor in 75.8% of cases (22 urologists). CONCLUSION: This study has shown that
      outpatient surgery accounted for a quarter of urologic surgery in Midi-Pyrenees
      region, and that the organization follows the recommendations of the
      International Association for Ambulatory Surgery. The main problems were the lack
      of information of the family doctor, and the lack of organized follow.
      Organizational problems were considered as the limiting factors of this activity
      development.

PMID- 24274950
TI  - [Ureteral metastasis of prostatic adenocarcinoma: case report and literature
      review].
AB  - Ureteral metastases of prostatic adenocarcinoma are very rare. We report the case
      of a 66-year-old man with a right ureteral metastasis of prostate cancer. Only 10
      cases have been reported in the literature these last 30 years. Most patients had
      a multimetastatic prostate cancer. Local treatment is not standardized.
      Hormonotherapy seems to be the most appropriate treatment in first intention.

PMID- 24274951
TI  - [Response to the comment to the laparoscopic nephrectomy for polycystic kidney is
      feasible and reproducible].

PMID- 24274952
TI  - 'Krokodil'--a designer drug from across the Atlantic, with serious consequences.

PMID- 24274953
TI  - Enrichment and partitioning of polycyclic aromatic hydrocarbons in the sea
      surface microlayer and subsurface water along the coast of Xiamen Island, China.
AB  - Sea microlayer (SML) and subsurface water (SSW) samples were collected around
      Xiamen Island to study the enrichment and partitioning of polycyclic aromatic
      hydrocarbons (PAHs). Total PAH concentrations ranged from 93.43 to 411.05 ng L(
      1) in the SML and 49.29-279.42 ng L(-1) in the SSW. Compared with the results of
      previous studies before pollution control measurements, PAHs levels decreased
      significantly. The enrichment factors (EFs) of dissolved and particulate PAHs
      varied from 0.68 to 2.71 and 0.43-3.56. EFs showed the consistent enrichment
      trends with sites and exhibited different enrichment characteristics between 2
      and 3 ring PAHs and 4 ring PAHs. Furthermore, the much higher concentrations of
      BaP (strong carcinogenicity) were accompanied by higher EFs in the SML samples
      from the Western Xiamen Harbour, which together indicated the risk of impacts to
      the fish eggs that usually float on the SML water after exposure to oil spills
      and combustion, contributed directly by the port and shipping activities.

PMID- 24274955
TI  - Comparison of skeletal anchored facemask and tooth-borne facemask according to
      vertical skeletal pattern and growth stage.
AB  - OBJECTIVE: To compare the treatment effects between skeletal anchored facemask
      (SAFM) and tooth-borne facemask (TBFM) on different maturation stages and
      vertical skeletal patterns. MATERIALS AND METHODS: In this retrospective study,
      28 patients who were treated with TBFM treatment and 19 patients who were treated
      with SAFM were reviewed. Cephalograms at the beginning and end of facemask
      application were obtained and assessed. Each treatment group was divided
      according to skeletal maturity and facial angle type. Nonparametric Mann-Whitney
      U-test was used for comparisons of maturity stage and vertical skeletal type
      between the treatment groups. RESULTS: SAFM produced a significant increase in
      the anterior-posterior position of orbitale (SNOr) and A point (N. per. to A).
      The high mandibular plane angle group of SAFM revealed greater anterior movement
      than that of TBFM without opening of the mandibular plane. In the SAFM group, the
      angulation of the maxillary incisors was retroclined at CVM3 compared to CVM4. In
      the younger group (CVM3), SAFM showed greater changes in the variables of
      orbitale (2.909 degrees ) and maxillary length (5.818 mm), compared to TBFM.
      CONCLUSIONS: Compared with the TBFM group, the findings suggest significant
      advantages for the SAFM group for relative skeletal maturity and vertical
      skeletal pattern.

PMID- 24274954
TI  - Sarcoplasmic reticulum Ca2+ cycling protein phosphorylation in a physiologic Ca2+
      milieu unleashes a high-power, rhythmic Ca2+ clock in ventricular myocytes:
      relevance to arrhythmias and bio-pacemaker design.
AB  - Basal phosphorylation of sarcoplasmic reticulum (SR) Ca(2+) proteins is high in
      sinoatrial nodal cells (SANC), which generate partially synchronized,
      spontaneous, rhythmic, diastolic local Ca(2+) releases (LCRs), but low in
      ventricular myocytes (VM), which exhibit rare diastolic, stochastic SR-generated
      Ca(2+) sparks. We tested the hypothesis that in a physiologic Ca(2+) milieu, and
      independent of increased Ca(2+) influx, an increase in basal phosphorylation of
      SR Ca(2+) cycling proteins will convert stochastic Ca(2+) sparks into periodic,
      high-power Ca(2+) signals of the type that drives SANC normal automaticity. We
      measured phosphorylation of SR-associated proteins, phospholamban (PLB) and
      ryanodine receptors (RyR), and spontaneous local Ca(2+) release characteristics
      (LCR) in permeabilized single, rabbit VM in physiologic [Ca(2+)], prior to and
      during inhibition of protein phosphatase (PP) and phosphodiesterase (PDE), or
      addition of exogenous cAMP, or in the presence of an antibody (2D12), that
      specifically inhibits binding of the PLB to SERCA-2. In the absence of the
      aforementioned perturbations, VM could only generate stochastic local Ca(2+)
      releases of low power and low amplitude, as assessed by confocal Ca(2+) imaging
      and spectral analysis. When the kinetics of Ca(2+) pumping into the SR were
      increased by an increase in PLB phosphorylation (via PDE and PP inhibition or
      addition of cAMP) or by 2D12, self-organized, "clock-like" local Ca(2+) releases,
      partially synchronized in space and time (Ca(2+) wavelets), emerged, and the
      ensemble of these rhythmic local Ca(2+) wavelets generated a periodic high
      amplitude Ca(2+) signal. Thus, a Ca(2+) clock is not specific to pacemaker cells,
      but can also be unleashed in VM when SR Ca(2+) cycling increases and spontaneous
      local Ca(2+) release becomes partially synchronized. This unleashed Ca(2+) clock
      that emerges in a physiological Ca(2+) milieu in VM has two faces, however: it
      can provoke ventricular arrhythmias; or if harnessed, can be an important feature
      of novel bio-pacemaker designs. 

PMID- 24274956
TI  - Maxillary incisor inclination of skeletal Class III patients treated with
      extraction of the upper first premolars and two-jaw surgery: conventional
      orthognathic surgery vs surgery-first approach.
AB  - OBJECTIVE: To investigate the differences in the amount and pattern of the
      maxillary incisor (MXI) inclination change in skeletal Class III patients treated
      with extraction of the maxillary first premolars (MXP1) and two-jaw surgery (TJS)
      between conventional orthognathic surgery (COS) and surgery-first approach (SFA).
      MATERIALS AND METHODS: The study included 60 skeletal Class III patients who had
      normal maxillary position, prognathic mandible, and mild crowding in the
      maxillary arch (<=4 mm). The patients were divided into group 1 (COS, n  =  36)
      and group 2 (SFA, n  =  24). Lateral cephalograms were taken before treatment
      (T0), 1 month before surgery (T1), within 1 month after surgery (T2), and after
      debonding (T3) for COS patients and at T0, T2, and T3 for SFA patients. After
      measurement of the skeletodental variables, statistical analyses were performed.
      RESULTS: During T0-T2, the amount of MXI inclination change (DeltaU1-SN) in group
      1 was significantly larger than that in group 2 (-12.8 degrees  vs -4.4 degrees ;
      P < .001). During T2-T3, DeltaU1-SN in groups 1 and 2 occurred in opposite
      directions (3.8 degrees  vs -5.9 degrees ; P < .001). However, the total amount
      of DeltaU1-SN during T0-T3 was not different between groups 1 and 2 (-9.0 degrees
      vs -10.3 degrees ). At T3 the U1-SN values for groups 1 and 2, respectively,
      moved closer to normal according to the values of the normal range rate (all
      83%), relative percentage ratio (102.4% and 100.1%), and achievement ratio (77.7%
      and 97.8%). CONCLUSIONS: The results of this study might provide basic data for
      predicting the amount and pattern of MXI inclination change in SFA for skeletal
      Class III TJS patients.

PMID- 24274957
TI  - Malocclusion and treatment need in children and adolescents with sickle cell
      disease.
AB  - OBJECTIVE: To assess the prevalence of malocclusion and treatment need in
      children and adolescents with sickle cell disease (SCD). MATERIALS AND METHODS:
      In this cross-sectional study, the sample size comprised 35 five-year-old
      children and 36 adolescents of both sexes, aged between 12 to 18 years, with SCD.
      Dental occlusion was assessed using two indexes: the Malocclusion Index (World
      Health Organization) and the Dental Aesthetic Index (DAI). RESULTS: The
      prevalence of malocclusion in the preschool children was 62.9%. The main
      malocclusions observed in this age group were Class II (37.1%), increased overjet
      (28.6%), reduced overbite (28.6%), and open bite (17.1%). In the 12- to 18-year
      old subjects, the prevalence of malocclusion was 100%, and the most prevalent
      types of malocclusion were maxillary overjet (63.9%) and maxillary misalignment
      (58.3%). It is noteworthy that the majority of adolescents (80.6%) had very
      severe or disabling malocclusions. CONCLUSION: The results revealed a high
      prevalence of malocclusion in children and adolescents with SCD. According to DAI
      score, the majority of the sample presented with very severe malocclusion and a
      compulsory treatment need.

PMID- 24274958
TI  - Modified tandem traction bow appliance compared with facemask therapy in treating
      Class III malocclusions.
AB  - OBJECTIVE: To compare the effects of the modified tandem traction bow appliance
      (MTTBA) and the facemask in treating patients with Class III malocclusion.
      MATERIALS AND METHODS: The material consisted of the pre-post treatment?pre-post
      observation lateral cephalograms of 65 subjects with skeletal and dental Class
      III malocclusion. In the first group 21 patients (mean age: 10 years, 6 months)
      were treated with a Delaire-type facemask (FM). In the second group 22 patients
      treated (mean age: 10 years) with MTTBA. The remaining 22 children (mean age: 9
      years, 7 months) were observed without treatment for 11 months. RESULTS: Increase
      in SNA, N-FH ? A, and ANB angles were significantly greater in the treatment
      groups compared to the control group. However, ANB angle showed a significantly
      greater increase in the FM group (2.8 +/- 0.30 degrees ) than in the MTTBA group
      (2.0 +/- 0.18 degrees ). The overjet and molar relation increased significantly
      in both treatment groups, but in the FM group (5.2 +/- 0.40 mm) increase in
      overjet was significantly greater than in the MTTBA group (4.0 +/- 0.27 mm).
      Mesial movement of upper molar and incisor were found to be greater in the FM
      group compared to the modified TTBA group. CONCLUSIONS: Both appliances were
      found to be effective in the treatment of Class III malocclusion. Their skeletal
      and dental effects showed differences due to their design.

PMID- 24274959
TI  - Encoding and reinstatement of threat: recognition potentials.
AB  - On a recognition test, stimuli originally encoded in the context of shock threat
      show an enhanced late parietal positivity during later recognition compared to
      stimuli encoded during safety, particularly for emotionally arousing stimuli. The
      present study investigated whether this ERP old/new effect is further influenced
      when a threat context is reinstated during the recognition test. ERPs were
      measured in a yes-no recognition test for words rated high or low in emotional
      arousal that were encoded and recognized in the context of cues that signaled
      threat of shock or safety. Correct recognition of words encoded under threat,
      irrespective of reinstatement, was associated with an enhanced old-new ERP
      difference (500-700ms; centro-parietal), and this difference was only reliable
      for emotionally arousing words. Taken together, the data suggest that information
      processed in a stressful context are associated with better recollection on later
      recognition, an effect that was not modulated by reinstating the stressful
      context at retrieval. 

PMID- 24274960
TI  - Risk factors of late-onset neonatal sepsis in Taiwan: A matched case-control
      study.
AB  - BACKGROUND: Infants in a neonatal intensive care unit (NICU) have a higher
      incidence of bloodstream infections (BSIs) than any other pediatric or adult
      population. The predisposing factors have not been comprehensively evaluated in
      this population in Taiwan. METHODS: A retrospective matched case-control study
      was conducted in the NICUs of a teaching hospital in Taiwan. The case patients
      were identified from a staff-maintained electronic database containing the
      records of BSIs from July 2003 to June 2006. The case patients and the control
      patients (who did not develop BSI during their NICU stay) were 1:1 matched by
      birth weight, gestational age, gender, Apgar score, and date of birth. RESULTS: A
      total of 164 infants with culture-proven BSI were identified. Of these, 74
      (45.1%) infants were female. The mean gestational age and birth weight were 30.7
      +/- 0.7 weeks and 1512 +/- 804 g, respectively. The common etiologic pathogens
      included coagulase-negative staphylococci (28.7%), Staphylococcus aureus (16.5%),
      and Klebsiella pneumoniae (14.6%). Candida spp. accounted for 11 (6.7%) episodes.
      Two independent factors associated with BSIs in the neonates, as identified by
      multivariate analysis using conditional logistic regression, were the use of
      parenteral nutrition (matched odds ratio [mOR], 6.07; 95% confidence interval
      [CI], 1.14-32.32; p = 0.034) and intraventricular hemorrhage (mOR, 2.68; 95% CI,
      1.20-5.99; p = 0.017). CONCLUSION: Parenteral nutrition was a significant and
      independent risk of late-onset neonatal sepsis. This risk should be considered
      when implementing early parenteral nutrition in NICUs.

PMID- 24274961
TI  - Aryl-substituted unsymmetrical benzothiadiazoles: synthesis, structure, and
      properties.
AB  - A family of unsymmetrical donor-acceptor, ferrocenyl-substituted
      benzothiadiazoles of types D1-pi-A-pi-D2, D1-pi-A1-pi-A2, D1-A-pi-D2, and D1-A1
      A2-D2, bearing a variety of electron-donating and electron-withdrawing groups,
      were designed and synthesized. Their photophysical, electrochemical, and
      computational properties were explored, which show strong donor-acceptor
      interaction. The presence of electron-rich units anthracene (6f) and
      triphenylamine (6h), and an electron-deficient unit 1,1,4,4-tetracyanobuta-1,3
      diene (TCBD) (9b) results in lowering of the band gap, which leads to a red shift
      of the absorption spectrum in these benzothiadiazole systems. The single crystal
      structures of 6c, 6g, 7a, and 7b are reported, which show marvelous
      supramolecular interactions. 

PMID- 24274962
TI  - Pubertal timing in girls and depression: a systematic review.
AB  - BACKGROUND: Because the incidence of depression increases after puberty, it is
      possible that pubertal timing in girls influences the onset of depression. Our
      objective was to assess the effect of early and late puberty in girls on the
      incidence of depression. METHODS: We systematically searched relevant databases
      for controlled studies that assessed the impact of pubertal timing in girls on
      the incidence of depression or depressive symptoms. The last search was completed
      in August 2013. Two authors selected the studies, extracted the data, and
      assessed the quality of the evidence. Meta-analyses of the adjusted and
      unadjusted results were calculated using random effects. RESULTS: Four cohort
      studies were included (n=8055 participants). Early puberty significantly
      increased the risk of new cases of depression in the unadjusted meta-analysis
      (RR=1.33; CI 95%: 1.02, 1.73) but not in the adjusted estimate of two of the
      included studies (RR=1.48; CI 95%: 0.69, 2.28). For late puberty, no significant
      associations were found (unadjusted RR=1.28; CI 95%: 0.87, 1.88). Two studies
      assessed the effect of early puberty on depressive symptoms and found positive
      associations. The quality of the available evidence was rated as very low.
      LIMITATIONS: The polled results had wide confidence intervals, and the available
      evidence was of very low quality. CONCLUSIONS: The available evidence supports
      little confidence regarding the impact of pubertal timing on the onset of
      depression in girls but suggests that early puberty in girls may increase the
      risk of depression. Further higher quality studies are needed to clarify the
      association between pubertal timing and the incidence of depression in girls and
      women.

PMID- 24274963
TI  - A multicentre randomised controlled trial of a carer supervised culturally
      adapted CBT (CaCBT) based self-help for depression in Pakistan.
AB  - BACKGROUND: Cognitive Behaviour Therapy (CBT) based self-help has been found to
      be effective for treating depression and anxiety. There is some evidence to
      suggest that CBT needs to be culturally adapted for it to be effective in non
      Western cultures. CBT is not widely used in low and middle income countries and
      there is a need to test its effectiveness in different settings and formats,
      including self-help. METHODS: We describe a RCT of a Culturally adapted CBT
      (CaCBT) based self-help manual in Pakistan. The trial was conducted in psychiatry
      departments in three cities. Assessments were carried out at baseline and at 12
      weeks, using Hospital Anxiety and Depression Scale, Bradford somatic Inventory
      and brief disability Questionnaire. RESULTS: At the end of the trial CaCBT based
      self-help was found to be effective against care as usual in reducing the
      symptoms of depression and anxiety, as well as somatic symptoms and disability.
      LIMITATIONS: This study was conducted only in secondary care and required either
      patient or a carer to be able to read and write. CONCLUSIONS: This is the first
      study outside West of a CBT based self-help intervention for depression. This
      study highlights the importance of using cost effective interventions in
      developing world in low intensity formats. Future studies should focus on trying
      these resources in different settings, like primary care, and with the use of
      audio/video or multimedia resources to improve compliance in patients with lower
      literacy.

PMID- 24274964
TI  - Type D personality in never-depressed patients and the development of major and
      minor depression after acute coronary syndrome.
AB  - BACKGROUND: Type D personality (TDP) has been proposed as a risk factor for the
      development of depressive symptoms after an acute coronary syndrome (ACS).
      However, contrasting findings emerged about its predicting power on the onset of
      depression, since an overlap between TDP and depressive symptoms has been
      proposed. The present study was aimed to verify whether TDP predicts the
      development of a depressive disorder in the 6 months after the discharge from
      hospital. METHODS: Two hundred fifty consecutive patients were recruited, at the
      Coronary Intensive Care Unit at the University Hospital of Parma, who were both
      presenting their first ACS and had no history of depression. The presence and the
      severity of major (MD) and minor (md) depression were evaluated with the Primary
      Care Evaluation of Mental Disorders (PRIME-MD) and the Hospital Anxiety and
      Depression Scale (HADS) respectively. Type D Personality was assessed with the
      DS14, both at baseline and at 1, 2, 4 and 6 month follow ups. RESULTS: Out of 250
      subjects (81.2% males), MD was diagnosed in 12 patients (4.8%) and md in 18
      patients (7.2%). At baseline risk factors for a post-ACS depressive disorder were
      HADS depression scores, whereas TDP, or its subscales, did not showed any effect.
      LIMITATION: The small amount of patients with incidence of depression, due to
      highly selective inclusion criteria, tempers the reliability of our results.
      CONCLUSION: Our data suggests that TDP does not predict the development of
      depressive disorders in never-depressed patients at their first ACS, when the
      baseline depression severity was controlled.

PMID- 24274965
TI  - How German children use intonation to signal information status in narrative
      discourse.
AB  - Recent research on adult German suggests that speakers use particular pitch
      accent types to signal the information status of discourse referents. This study
      investigates to what extent German five- and seven-year-olds have acquired this
      mapping. Semi-natural speech data was obtained from a picture-elicited narration
      task in which the information status was systematically varied. Surprisingly,
      data from an adult control group were inconsistent with the claim of a clear
      status-accent mapping, and demonstrated that adult scripted speech cannot be
      taken as a target model. However, compared with adults' unscripted speech
      productions, children were indeed adult-like in their information status marking.
      Both child groups accented new referents, but tended to deaccent given referents.
      Accessible referents (whose first mentions were less recent) were mostly realized
      like new referents. Differences between adults and children emerged in the use of
      intonation to structure narrations, suggesting that some functions of intonation
      may be acquired only later.

PMID- 24274966
TI  - Molecular basis of cancer-therapy-induced cardiotoxicity: introducing microRNA
      biomarkers for early assessment of subclinical myocardial injury.
AB  - Development of reliable biomarkers for early clinical assessment of drug-induced
      cardiotoxicity could allow the detection of subclinical cardiac injury risk in
      vulnerable patients before irreversible damage occurs. Currently, it is difficult
      to predict who will develop drug-induced cardiotoxicity owing to lack of
      sensitivity and/or specificity of currently used diagnostics. miRNAs are mRNA
      regulators and they are currently being extensively profiled for use as
      biomarkers due to their specific tissue and disease expression signature
      profiles. Identification of cardiotoxicity-specific miRNA biomarkers could
      provide clinicians with a valuable tool to allow prognosis of patients at risk of
      cardiovascular injury, alteration of a treatment regime or the introduction of an
      adjunct therapy in order to increase the long-term survival rate of patients
      treated with cardiotoxic drugs. 

PMID- 24274967
TI  - Statins and the autonomic nervous system.
AB  - Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma
      cholesterol and improve endothelium-dependent vasodilation, inflammation and
      oxidative stress. A 'pleiotropic' property of statins receiving less attention is
      their effect on the autonomic nervous system. Increased central sympathetic
      outflow and diminished cardiac vagal tone are disturbances characteristic of a
      range of cardiovascular conditions for which statins are now prescribed routinely
      to reduce cardiovascular events: following myocardial infarction, and in
      hypertension, chronic kidney disease, heart failure and diabetes. The purpose of
      the present review is to synthesize contemporary evidence that statins can
      improve autonomic circulatory regulation. In experimental preparations, high-dose
      lipophilic statins have been shown to reduce adrenergic outflow by attenuating
      oxidative stress in central brain regions involved in sympathetic and
      parasympathetic discharge induction and modulation. In patients with
      hypertension, chronic kidney disease and heart failure, lipophilic statins, such
      as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle
      sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin
      therapy on HRV (heart rate variability) are less consistent. Because of their
      implications for BP (blood pressure) control, insulin sensitivity,
      arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions
      should be considered additional mechanisms by which statins lower cardiovascular
      risk.

PMID- 24274969
TI  - Determinants of daytime sleepiness in first-year nursing students: a
      questionnaire survey.
AB  - BACKGROUND: Daytime sleepiness may affect student learning achievement. Research
      studies have found that daytime sleepiness is common in university students;
      however, information regarding the determinants of daytime sleepiness in this
      population is still lacking. OBJECTIVES: The purpose of this study was to
      investigate the determinants of daytime sleepiness in first-year nursing
      students. In particular, we looked for the relationship between perceived
      symptoms, nocturnal sleep quality, and daytime sleepiness. DESIGN: A cross
      sectional and correlational design was employed. PARTICIPANTS AND METHOD:
      Participants were recruited from two nursing programs at an institute of
      technology located in southern Taiwan. Ninety-three nursing students completed
      the questionnaires one month after enrollment into their program. RESULTS:
      Approximately 35% of the participants experienced excessive daytime sleepiness at
      the beginning of the semester. Six variables (joining a student club, perceived
      symptoms, daytime dysfunction, sleep disturbances, sleep latency, and subjective
      sleep quality) were significantly correlated with daytime sleepiness. Among them,
      daytime dysfunction and perceived symptoms were two major determinants of daytime
      sleepiness, both accounting for 37.2% of the variance. CONCLUSIONS: Daytime
      sleepiness in students should not be ignored. It is necessary to help first-year
      students identify and mitigate physical and psychological symptoms early on, as
      well as improve daytime functioning, to maintain their daytime performance and
      promote learning achievement.

PMID- 24274970
TI  - Increased serum chemerin level promotes cellular invasiveness in gastric cancer:
      a clinical and experimental study.
AB  - This study sought to determine the serum levels of chemerin in gastric cancer
      patients and healthy subjects and to investigate the biological effect of
      chemerin on gastric cancer cells. Serum chemerin level of 36 gastric cancer
      patients and 40 healthy subjects was measured by enzyme-linked immunosorbent
      assay. AGS and MKN28 cells were treated with recombinant human chemerin, MAPKs
      phosphorylation was then measured. Chemerin were added to culture medium of AGS
      and MKN28 in the absence or presence of MAPK inhibitors, VEGF, MMP-7, IL-6 and
      cell invasiveness assay were then performed. Serum level of chemerin was
      significantly higher in gastric cancer patients than healthy subjects (P<0.01).
      The elevation of serum chemerin level was associated with advanced clinical
      stages and nonintestinal type of gastric cancer. Chemerin increased invasiveness
      of gastric cancer cells. Chemerin induced phosphorylation of p38 and ERK1/2 MAPKs
      and upregulated VEGF, MMP-7 and IL-6. Inhibition of ERK1/2 phosphorylation
      abolished the upregulation of VEGF, MMP-7 and IL-6 and the pro-invasive effect of
      chemerin. This study demonstrates a novel action of chemerin in gastric
      carcinogenesis. 

PMID- 24274971
TI  - Purified PEGylated porcine glucagon-like peptide-2 reduces the severity of
      colonic injury in a murine model of experimental colitis.
AB  - The rapid degradation of porcine glucagon-like peptide-2 (pGLP-2) by the enzyme
      dipeptidyl peptidase-IV (DPP-IV) is the main impediment in the development of
      pGLP-2 as a potential therapeutic agent for intestinal dysfunction and damage. In
      this study, one mono-modified Lys(30)-polyethylene glycol (PEG)-pGLP-2 was
      prepared using mPEG-succinimidyl propionate. To determine the optimized condition
      for PEGylation, the reactions were monitored by RP-HPLC and MALDI-TOF-MS.
      Stability was tested in purified DPP-IV in vitro. In vivo, the protective effects
      for colonic injury were measured in dextran sulfate sodium (DSS)-induced colitis
      in mice. The monoPEGylated products reached the maximum yield at 4:1 ratio of
      mPEG5k-SPA to pGLP-2. An effective method of successfully separating PEGylated
      pGLP-2 from mPEG-SPA5kD using CM Sepharose Fast Flow resin was established. The
      half-life of Lys(30)-PEG-pGLP-2 was 16-fold longer than that of pGLP-2 in DPP-IV.
      The DSS mice exhibited marked weight loss), which was significantly reduced by
      Lys(30)-PEG-pGLP-2 therapy. DSS treatment significantly increased colonic damage
      score, which was significantly reduced by administration of Lys(30)-PEG-pGLP-2 in
      DSS-mice. DSS-induced colitis clearly induced Myeloperoxidase activity in the
      colon, which was significantly reduced by treatments with 3% DSS-pGLP-2 or 3% DSS
      PEG-pGLP-2. These results showed that site-specific Lys(30)-PEG-GLP-2 was
      resistant to degradation and reduced the severity of colonic injury in murine
      colitis. The enhanced biological potency of this product highlighted its
      potential as a therapeutic agent for intestinal diseases. 

PMID- 24274972
TI  - A case of phrynoderma in a patient with Crohn's disease.
AB  - Phrynoderma is a type of follicular hyperkeratosis associated with nutritional
      deficiencies. It is rarely seen in developed countries, although cases have been
      reported in patients with severe malnutrition or malabsorption secondary to
      various causes. This report describes a 19-year-old patient with poorly
      controlled Crohn's disease and malnutrition who developed the characteristic
      hyperkeratotic papules and plaques on his trunk and extremities in the setting of
      low serum vitamin A levels. To our knowledge, there are no reports of phrynoderma
      associated with Crohn's disease. It is likely that our patient's low vitamin A
      level and subsequent phrynoderma was the result of increased Crohn's disease
      activity and malnutrition. 

PMID- 24274973
TI  - Electronic cigarette use among Korean adolescents: a cross-sectional study of
      market penetration, dual use, and relationship to quit attempts and former
      smoking.
AB  - PURPOSE: As elsewhere, in South Korea electronic cigarettes (e-cigarettes) are
      marketed, in part, as a smoking cessation aid. We assessed the prevalence of e
      cigarette use among Korean adolescents and the relationship between e-cigarette
      use and current (past 30-day) smoking, cigarettes/day, attempts to quit
      conventional cigarettes, and ceasing to use cigarettes. METHODS: Data from the
      2011 Korean Youth Risk Behavior Web-based Survey of 75,643 students aged 13-18
      years were analyzed with logistic regression. RESULTS: A total of 9.4% (8.0% ever
      dual users who were concurrently using e-cigarettes and smoking conventional
      cigarettes and 1.4% ever-e-cigarette only users) of Korean adolescents have ever
      used e-cigarettes and 4.7% were current (past 30-day) e-cigarette users (3.6%
      dual users and 1.1% e-cigarettes only). After adjusting for demographics, current
      cigarette smokers were much more likely to use e-cigarettes than were nonsmokers.
      Among current cigarette smokers, those who smoked more frequently were more
      likely to be current e-cigarette users. The odds of being an e-cigarette user
      were 1.58 times (95% confidence interval, 1.39-1.79) higher among students who
      had made an attempt to quit than for those who had not. It was rare for students
      no longer using cigarettes to be among current e-cigarette users (odds ratio,
      .10; confidence interval, .09-.12). CONCLUSIONS: Some Korean adolescents may be
      responding to advertising claims that e-cigarettes are a cessation aid: those who
      had made an attempt to quit were more likely to use e-cigarettes but less likely
      to no longer use cigarettes. E-cigarette use was strongly associated with current
      and heavier cigarette smoking.

PMID- 24274974
TI  - Effect of upper strap downward displacement on n95 filtering facepiece respirator
      fit factors: a pilot study.
AB  - Fifteen subjects underwent three replicates of quantitative respirator fit
      testing with N95 filtering facepiece respirators that were donned with the upper
      strap high on the occiput, as per the manufacturers' donning instructions. Each
      fit-test was immediately followed by repeat fit-testing with the upper strap
      downwardly displaced to the level of the ear sulcus to determine any change in
      fit factors that might occur with upper strap downward slippage. A total of 35/45
      (78%) initial fit-tests had a passing score (fit factor >= 100) with the top
      strap high on the occiput and 33/35 (94%) of these passed subsequent fit-testing
      after the top strap was displaced downward to the ear sulcus. Geometric mean fit
      factors for the initial passed fit-tests, and following downward strap
      displacement, were 217 +/- 1.6 and 207 +/- 1.9, respectively (p = 0.64). Downward
      displacement of the top strap did not significantly impact fit factors of N95
      FFRs that had previously passed fit-testing.

PMID- 24274975
TI  - Autoimmune thyroiditis: Centennial jubilee of a social disease and its
      comorbidity.
AB  - The history of autoimmune thyroiditis (AIT) and its role in pathophysiology of
      transition from adolescent hypothalamic syndrome (obesity with rose striae) into
      early metabolic syndrome is reviewed. Marfanoid phenotype and chronic
      disequilibrium between local, autacoid-mediated and systemic, hormone-mediated
      regulation, typical for inherited connective tissue disorders, may promote this
      transition. Pathogenetic roles of hyperprolactinemia and cytokine misbalance are
      evaluated and discussed in its pathogenesis. 

PMID- 24274976
TI  - The influence of YS-1 on the Dll4-Notch1 signaling pathway.
AB  - In this study, we investigated the role and molecular mechanism of p43 and YS-1
      (recombinant human p43 protein) in Dll4-Notch1 signaling pathway. Active, small
      interfering RNA and recombinant plasmid targeting of p43 protein were used to
      infect human umbilical vein endothelial cells (HUVECs). Three-dimensional
      sprouting model, endothelial cell migration assay, and sprouting and tube
      formation assay were used to deduce the function of p43 and YS-1 in angiogenesis.
      Semi-quantitative reverse transcription-polymerase chain reaction and western
      blot analysis were performed to detect the efficiency of p43 in Dll4-Notch1
      signaling in HUVECs. It was found that silencing and overexpression of p43 could
      upregulate Dll4-Notch and stimulate angiogenesis. p43 plays a complex role in
      angiogenesis. When the concentration is under 100 nM, it promotes angiogenesis;
      instead, when the concentration is over 100 nM, it inhibits angiogenesis. In this
      study, we found that the expression level of p43 was under 60 nM. However,
      recombinant human p43 protein, YS-1, inhibited endothelial cell sprouting, and
      500 MUg/ml of YS-1 attenuated the activation of Dll4-Notch1 signaling. These
      results suggested that YS-1 could directly inhibit angiogenesis through Dll4
      Notch1 signal transduction pathway, while p43 plays a modulating role in this
      signaling pathway. 

PMID- 24274978
TI  - Neutral-like abundance distributions in the presence of selection in a continuous
      fitness landscape.
AB  - The neutral theory of biodiversity has successfully explained the observed
      composition of many ecological communities but it relies on strict demographic
      equivalence among species and provides no room for evolutionary processes such as
      selection and adaptation. Here we show how to embed the neutral theory within the
      Darwinian framework. In a continuous fitness landscape with a quadratic maximum,
      typical for quantitative traits, selection does restrict the extant species to
      have trait values close to optimal, but due to the continuous nature of the
      landscape, there are always many such species available, and so competition among
      them is effectively neutral. For sufficiently small mutational steps, the
      community structure fits perfectly to the Fisher log-series species abundance
      distribution. In general, the selection-mutation process, when superimposed on
      demographic and environmental noise, yields a small set of characteristic
      patterns for species abundance curves. A survey of these patterns is given. 

PMID- 24274977
TI  - Diagnosis and treatment strategies for community-acquired Streptococcus
      salivarius meningitis.

PMID- 24274979
TI  - [Maple syrup urine disease caused by a new mutation: C.1128-1130delCinsTT].

PMID- 24274980
TI  - Type 1 diabetes, metabolic syndrome and cardiovascular risk.
AB  - Patients with type 1 diabetes mellitus (T1DM) traditionally had a low body mass
      index and microangiopathic complications were common, while macroangiopathy and
      the metabolic syndrome were exceptional. The Diabetes Control and Complications
      Trial, published in 1993, demonstrated that therapy aimed at maintaining HbA1c
      levels as close to normal as feasible reduced the incidence of microangiopathy.
      Since then, the use of intensive insulin therapy to optimize metabolic control
      became generalized. Improved glycemic control resulted in a lower incidence of
      microangiopathy; however, its side effects included a higher rate of severe
      hypoglycemia and increased weight gain. Approximately 50% of patients with T1DM
      are currently obese or overweight, and between 8% and 40% meet the metabolic
      syndrome criteria. The components of the metabolic syndrome and insulin
      resistance have been linked to chronic T1DM complications, and cardiovascular
      disease is now the leading cause of death in these patients. Therefore, new
      therapeutic strategies are required in T1DM subjects, not only to intensively
      lower glycemia, but to control all associated metabolic syndrome traits. 

PMID- 24274981
TI  - Use of in silico tools for classification of novel missense mutations identified
      in dystrophin gene in developing countries.
AB  - DMD gene which is composed of 79 exons is the largest known gene located on X
      chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30
      35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is
      costly in developing countries, therefore, a few of the exons are selected to be
      analyzed routinely in clinical laboratories. In this study, direct sequencing was
      used for detection of point mutations in 10 exons of dystrophin gene in patients
      affected with DMD without detectable large rearrangements. Freely available
      programs were used to predict the damaging effects of the mutations. Point
      mutations were successfully detected in three patients. Three novel mutations,
      two missense mutations located on nonconservative domains and a single nucleotide
      deletion, were detected. Missense mutations were predicted to change splicing
      efficiency. Detection of point mutations by DNA analysis followed by prediction
      of the pathogenecity by using bioinformatic tool might be an asset to provide
      proper diagnosis or genetic counseling to patients and their family. 

PMID- 24274982
TI  - Analysis of donor and recipient ABO incompatibility and antibody-associated
      complications after allogeneic stem cell transplantation with reduced-intensity
      conditioning.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) can be performed across
      the ABO blood group barrier. The impact of ABO incompatibility on clinical
      outcome is controversial. A retrospective analysis of 310 patients who underwent
      HSCT with reduced-intensity conditioning between 1998 and 2011 was performed to
      investigate the frequency and clinical implications of anti-RBC antibodies in
      passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or
      recurring recipient type ABO antibodies (PRABO) after major ABO mm HSCT, and
      autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical
      outcome were analyzed by univariate and multivariate analysis for groups with or
      without anti-RBC antibodies. ABO blood group incompatibility did not affect
      clinical outcome despite an increased requirement of blood transfusion. Twelve
      patients with AIHA, 6 patients with PLS, and 12 patients with PRABO post-HSCT
      were identified. AIHA did not affect overall survival (OS) or transplant-related
      mortality (TRM), but patients with AIHA had a lower incidence of grades II to IV
      acute graft-versus-host disease (P = .05). OS in the PLS group was 0% compared
      with 61% in the whole group receiving minor ABO mm transplants (P < .001).
      Comparing PRABO patients with those receiving a major ABO mm HSCT, the OS was 17%
      versus 73% (P = .002) and TRM was 50% versus 21% (P = .03). At our center, PLS
      after minor ABO mm and PRABO antibodies after major ABO mm HSCT are significant
      risk factors for decreased OS and TRM. Our results suggest that occurrence of
      unexpected ABO antibodies after HSCT warrant a wider investigation individual to
      find the underlying cause. 

PMID- 24274983
TI  - Autoimmune hematological diseases after allogeneic hematopoietic stem cell
      transplantation in children: an Italian multicenter experience.
AB  - Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic
      stem cell transplantation (HSCT), but reports on these complications in large
      cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574
      consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three
      children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune
      thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%),
      and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5%
      (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of
      alternative donor and nonmalignant disease was statistically associated with
      AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained
      complete remission was achieved in 87% of cases with the anti-CD20 monoclonal
      antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans'
      syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD
      diagnosis as a direct or indirect consequence of their disorder. Our data suggest
      that AHDs are a relatively rare complication occurring after HSCT that usually
      respond to treatment with rituximab. 

PMID- 24274984
TI  - Role of cortactin in dynamic actin remodeling events in gonadotrope cells.
AB  - GnRH induces marked activation of the actin cytoskeleton in gonadotropes;
      however, the physiological consequences and cellular mechanisms responsible have
      yet to be fully elucidated. The current studies focus on the actin scaffolding
      protein cortactin. Using the gonadotrope-derived alphaT3-1 cell line, we found
      that cortactin is phosphorylated at Y(421), S(405), and S(418) in a time
      dependent manner in response to the GnRH agonist buserelin (GnRHa). GnRHa induced
      translocation of cortactin to the leading edge of the plasma membrane where it
      colocalizes with actin and actin-related protein 3 (Arp3). Incubation of alphaT3
      1 cells with the c-src inhibitor phosphoprotein phosphatase 1, blocked tyrosine
      phosphorylation of cortactin, reduced cortactin association with Arp3, and
      blunted actin reorganization in response to GnRHa. Additionally, we used RNA
      silencing strategies to knock down cortactin in alphaT3-1 cells. Knockdown of
      cortactin blocked the ability of alphaT3-1 cells to generate filopodia,
      lamellipodia, and membrane ruffles in response to GnRHa. We show that
      lamellipodia and filopodia are capable of LHbeta mobilization in primary
      pituitary culture after GnRHa treatment, and disruption of these structures using
      jasplakinolide reduces LH secretion. Collectively, our findings suggest that
      after GnRHa activation, src activity leads to tyrosine phosphorylation of
      cortactin, which facilitates its association with Arp3 to engage the actin
      cytoskeleton. The reorganization of actin by cortactin potentially underlies
      GnRHa-induced secretory events within alphaT3-1 cells. 

PMID- 24274985
TI  - 17beta-estradiol replacement reverses age-related lung disease in estrogen
      deficient C57BL/6J mice.
AB  - The role that estrogens play in the aging lung is poorly understood. Remodeling
      of the aging lung with thickening of the alveolar walls and reduction in the
      number of peripheral airways is well recognized. The present study was designed
      to address whether estrogen deficiency would affect age-associated changes in the
      lungs of female C57BL/6J mice. Lungs isolated from old mice (24 months old,
      estrogen-deficient) demonstrated decreased lung volume and decreased alveolar
      surface area. There was no difference in alveolar number in the lungs of old and
      young mice (6 months old, estrogen-replete). Estrogen replacement restored lung
      volume, alveolar surface area, and alveolar wall thickness to that of a young
      mouse. Estrogen receptor-alpha (ERalpha) protein expression increased without a
      change in ERbeta protein expression in the lung tissue isolated from old mice. In
      the lungs of old mice, the number of apoptotic cells was increased as well as the
      activation of matrix metalloproteinase-2 and ERK. Young mice had the highest
      serum 17beta-estradiol levels that decreased with age. Our data suggest that in
      the aging female mouse lung, estrogen deficiency and an increase of ERalpha
      expression lead to the development of an emphysematous phenotype. Estrogen
      replacement partially prevents these age-associated changes in the lung
      architecture by restoration of interalveolar septa. Understanding the role of
      estrogens in the remodeling of the lung during aging may facilitate interventions
      and therapies for aging-related lung disease in women. 

PMID- 24274986
TI  - Accurate prediction of polarised high order electrostatic interactions for
      hydrogen bonded complexes using the machine learning method kriging.
AB  - As intermolecular interactions such as the hydrogen bond are electrostatic in
      origin, rigorous treatment of this term within force field methodologies should
      be mandatory. We present a method able of accurately reproducing such
      interactions for seven van der Waals complexes. It uses atomic multipole moments
      up to hexadecupole moment mapped to the positions of the nuclear coordinates by
      the machine learning method kriging. Models were built at three levels of theory:
      HF/6-31G(**), B3LYP/aug-cc-pVDZ and M06-2X/aug-cc-pVDZ. The quality of the
      kriging models was measured by their ability to predict the electrostatic
      interaction energy between atoms in external test examples for which the true
      energies are known. At all levels of theory, >90% of test cases for small van der
      Waals complexes were predicted within 1 kJ mol(-1), decreasing to 60-70% of test
      cases for larger base pair complexes. Models built on moments obtained at B3LYP
      and M06-2X level generally outperformed those at HF level. For all systems the
      individual interactions were predicted with a mean unsigned error of less than 1
      kJ mol(-1).

PMID- 24274987
TI  - Amniotic fluid infection, inflammation, and colonization in preterm labor with
      intact membranes.
AB  - OBJECTIVE: The purpose of this study was to compare intraamniotic inflammation vs
      microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome
      in preterm labor with intact membranes. STUDY DESIGN: Interleukin-6 (IL-6) was
      measured in prospectively collected amniotic fluid from 305 women with preterm
      labor. MIAC was defined by amniotic fluid culture and/or detection of microbial
      16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6,
      >=11.3 ng/mL); severe inflammation (no MIAC; IL-6, >=11.3 ng/mL); mild
      inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6
      ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS: The infection (n = 27) and
      severe inflammation (n = 36) groups had similar latency (median, <1 day and 2
      days, respectively) and similar rates of composite perinatal morbidity and
      mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n =
      195) groups had similar outcomes (median latency, 23.5 and 25 days; composite
      morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation
      (n = 47) groups had outcomes that were intermediate to the severe inflammation
      and negative groups (median latency, 7 days; composite morbidity and mortality
      rates, 53%). In logistic regression adjusting for gestational age at enrollment,
      IL-6 >=11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with
      composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence
      interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5,
      respectively). CONCLUSION: We confirmed previous reports that intraamniotic
      inflammation is associated with adverse perinatal outcomes whether or not
      intraamniotic microbes are detected. Colonization without inflammation appears
      relatively benign. Intraamniotic inflammation is not simply present or absent but
      also has degrees of severity that correlate with adverse outcomes. We propose the
      designation amniotic inflammatory response syndrome to denote the adverse
      outcomes that are associated with intraamniotic inflammation.

PMID- 24274988
TI  - Specific rare cell capture using micro-patterned silicon nanowire platform.
AB  - We report on the rapid and direct quantification of specific cell captures using
      a micro-patterned streptavidin (STR)-functionalized silicon nanowire (SiNW)
      platform, which was prepared by Ag-assisted wet chemical etching and a photo
      lithography process. This platform operates by high-affinity cell capture
      rendered by the combination of antibody-epithelial cell surface-binding, biotin
      streptavidin binding, and the topologically enhanced cell-substrate interaction
      on a 3-dimensional SiNWs array. In this work, we developed a micro-patterned
      nanowire platform, with which we were able to directly evaluate the performance
      enhancement due to nanotopography. An excellent capture efficiency of ~96.6+/
      6.7%, which is the highest value achieved thus far for the targeting specific
      A549 cells on a selective area of patterned SiNWs, is demonstrated. Direct
      comparison between the nanowire region and the planar region on the same
      substrate indicates dramatically elevated cell-capture efficiency on
      nanotopological surface identical surface chemistry (<2% cell-capture
      efficiency). An excellent linear response was seen for quantifying captured A549
      cells with respect to loaded cells. This study suggests that the micro-patterned
      STR-functionalized SiNWs platform provides additional advantage for detecting
      rare cells populations in a more quantitative and specific manner. 

PMID- 24274989
TI  - Tumoral melanosis in an adolescent after trauma: a clinicopathological dilemma.
AB  - Tumoral melanosis (TM) is a histologic term used to indicate a nodular
      accumulation of melanophages in the dermis clinically presenting as a pigmented
      lesion. It is usually associated with regression of melanoma and nonmelanoma
      melanocytic pigmented lesions. We present the case of a 16-year-old girl with a
      suspicious pigmented macule on her right knee that appeared after trauma. The
      lesion was completely excised and diagnosed as TM. 

PMID- 24274990
TI  - Association between gene variants and response to buprenorphine maintenance
      treatment.
AB  - A variety of studies were addressed to differentiate responders and non
      responders to substitution treatment among heroin dependent patients, without
      conclusive findings. In particular, preliminary pharmacogenetic findings have
      been reported to predict treatment effectiveness in mental health and substance
      use disorders. Aim of the present study was to investigate the possible
      association of buprenorphine (BUP) treatment outcome with gene variants that may
      affect kappa-opioid receptors and dopamine system function. One hundred and seven
      heroin addicts (West European, Caucasians) who underwent buprenorphine
      maintenance treatment were genotyped and classified into two groups (A and B) on
      the basis of treatment outcome. Non-responders to buprenorphine (group B) have
      been identified taking into account early drop out, continuous use of heroin,
      severe behavioral or psychiatric problems, misbehavior and diversion during the 6
      months treatment period. No difference was evidenced between responders and non
      responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP.
      The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1),
      allele 10, was evidently much higher in "non-responder" than in "responder"
      individuals (64.9% vs. 55.93%) whereas the frequency of the category of other
      alleles (6, 7 and 11) was higher in responder than in non-responder individuals
      (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene
      related changes in kappa-opioid receptor could consistently affect buprenorphine
      pharmacological action and clinical effectiveness was not confirmed in our study,
      at least in relation to the single nucleotide polymorphism 36G>T. On the other
      hand, the possibility that gene-related dopamine changes could have reduced BUP
      effectiveness and impaired maintenance treatment outcome was cautiously supported
      by our findings. DAT1 gene variants such as allele 10, previously reported in
      association with personality and behavioral problems, would have influenced the
      effects of BUP-induced dopamine release, modulated through mu and kappa opioid
      receptors, and probably the related reinforcing capacity of the drug. 

PMID- 24274991
TI  - Postpartum depression: identifying associations with bipolarity and personality
      traits. Preliminary results from a cross-sectional study in Poland.
AB  - The goals of this study have been to determine the prevalence of the bipolar
      spectrum features in the population of women with postpartum depression (PPD)
      symptoms, as well as to analyze the personality differences between putative
      'unipolar' and 'bipolar' PPD subjects. The sample enrolled into the cross
      sectional study consisted of 344 women at 6-12 weeks postpartum. The authors used
      the Edinburgh Postnatal Depression Scale (EPDS; cut-off score: 13 pts.) for the
      assessment of the PPD symptoms, the Mood Disorder Questionnaire (MDQ; cut-off
      scores: 7 or 8 pts.) for diagnosing the bipolar features, and the NEO-Five Factor
      Inventory (NEO-FFI) for the assessment of personality traits. The EPDS-positive
      subjects were more likely to score positively on the MDQ, as compared to the EPDS
      negative ones. The EPDS-positive subjects who also scored >=8 pts. on the MDQ
      were characterized by higher index of neuroticism, as compared to those who
      scored positively on the EPDS only. The results suggest that the presence of PPD
      symptoms is related to significantly higher scores of bipolarity and neuroticism.
      The more robust trait of neuroticism might be a marker of the 'bipolar' PPD, as
      compared to the 'unipolar' form of the disorder. 

PMID- 24274992
TI  - Prediction of bone strength by MUCT and MDCT-based finite-element-models: how
      much spatial resolution is needed?
AB  - OBJECTIVES: Finite-element-models (FEM) are a promising technology to predict
      bone strength and fracture risk. Usually, the highest spatial resolution
      technically available is used, but this requires excessive computation time and
      memory in numerical simulations of large volumes. Thus, FEM were compared at
      decreasing resolutions with respect to local strain distribution and prediction
      of failure load to (1) validate MDCT-based FEM and to (2) optimize spatial
      resolution to save computation time. MATERIALS AND METHODS: 20 cylindrical
      trabecular bone specimens (diameter 12 mm, length 15-20mm) were harvested from
      elderly formalin-fixed human thoracic spines. All specimens were examined by
      micro-CT (isotropic resolution 30 MUm) and whole-body multi-row-detector computed
      tomography (MDCT, 250 MUm * 250 MUm * 500 MUm). The resolution of all datasets
      was lowered in eight steps to ~ 2,000 MUm * 2000 MUm * 500 MUm and FEM were
      calculated at all resolutions. Failure load was determined by biomechanical
      testing. Probability density functions of local micro-strains were compared in
      all datasets and correlations between FEM-based and biomechanically measured
      failure loads were determined. RESULTS: The distribution of local micro-strains
      was similar for micro-CT and MDCT at comparable resolutions and showed a shift
      toward higher average values with decreasing resolution, corresponding to the
      increasing apparent trabecular thickness. Small micro-strains (epsiloneff<0.005)
      could be calculated down to 250 MUm * 250 MUm * 500 MUm. Biomechanically
      determined failure load showed significant correlations with all FEM, up to
      r=0.85 and did not significantly change with lower resolution but decreased with
      high thresholds, due to loss of trabecular connectivity. CONCLUSION: When
      choosing connectivity-preserving thresholds, both micro-CT- and MDCT-based finite
      element-models well predicted failure load and still accurately revealed the
      distribution of local micro-strains in spatial resolutions, available in vivo
      (250 MUm * 250 MUm * 500 MUm), that thus seemed to be the optimal compromise
      between high accuracy and low computation time.

PMID- 24274993
TI  - Prenatal and mental health care among trauma-exposed, HIV-infected, pregnant
      women in the United States.
AB  - Comprehensive prenatal care for HIV-infected women in the United States involves
      addressing mental health needs. Retrospective quantitative data are presented
      from HIV-infected pregnant women (n = 45) who reported childhood sexual or
      physical abuse (66%), abuse in adulthood by a sexual partner (25%), and abuse
      during pregnancy (10%). Depression and anxiety were the most commonly reported
      psychological symptoms; more than half of the sample reported symptoms of
      posttraumatic stress disorder (PTSD), including HIV-related PTSD (PTSD-HIV).
      There was a strong association between depression and PTSD as well as between
      anxiety and PTSD-HIV. The majority of infants received zidovudine at birth and
      continued the recommended regimen. All but one infant were determined to be
      noninfected. Women improved their CD4(+) T cell counts and HIV RNA viral loads
      while in prenatal care. Results support the need for targeted prenatal programs
      to address depression, anxiety, substance use, and trauma in HIV-infected women. 

PMID- 24274994
TI  - The Cochrane Collaboration and evidence-based practice: where the art and science
      of HIV nursing meet.

PMID- 24274995
TI  - Transgenic overexpression of the presynaptic choline transporter elevates
      acetylcholine levels and augments motor endurance.
AB  - The hemicholinium-3 (HC-3) sensitive, high-affinity choline transporter (CHT)
      sustains cholinergic signaling via the presynaptic uptake of choline derived from
      dietary sources or from acetylcholinesterase (AChE)-mediated hydrolysis of
      acetylcholine (ACh). Loss of cholinergic signaling capacity is associated with
      cognitive and motor deficits in humans and in animal models. Whereas genetic
      elimination of CHT has revealed the critical nature of CHT in maintaining ACh
      stores and sustaining cholinergic signaling, the consequences of elevating CHT
      expression have yet to be studied. Using bacterial artificial chromosome (BAC)
      mediated transgenic methods, we generated mice with integrated additional copies
      of the mouse Slc5a7 gene. BAC-CHT mice are viable, appear to develop normally,
      and breed at wild-type (WT) rates. Biochemical studies revealed a 2 to 3-fold
      elevation in CHT protein levels in the CNS and periphery, paralleled by
      significant increases in [(3)H]HC-3 binding and synaptosomal choline transport
      activity. Elevations of ACh in the BAC-CHT mice occurred without compensatory
      changes in the activity of either choline acetyltransferase (ChAT) or AChE.
      Immunohistochemistry for CHT in BAC-CHT brain sections revealed markedly elevated
      CHT expression in the cell bodies of cholinergic neurons and in axons projecting
      to regions known to receive cholinergic innervation. Behaviorally, BAC-CHT mice
      exhibited diminished fatigue and increased speeds on the treadmill test without
      evidence of increased strength. Finally, BAC-CHT mice displayed elevated
      horizontal activity in the open field test, diminished spontaneous alteration in
      the Y-maze, and reduced time in the open arms of the elevated plus maze.
      Together, these studies provide biochemical, pharmacological and behavioral
      evidence that CHT protein expression and activity can be elevated beyond that
      seen in wild-type animals. BAC-CHT mice thus represent a novel tool to examine
      both the positive and negative impact of constitutively elevated cholinergic
      signaling capacity. 

PMID- 24274996
TI  - Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing
      anti-inflammatory responses.
AB  - Multiple sclerosis (MS) is a common inflammatory and demyelinating neurological
      disease. Experimental autoimmune encephalomyelitis (EAE), an animal model of MS,
      has been widely used to test MS treatment methods. Ulinastatin (UTI), a drug used
      to treat acute inflammatory disorders, has been tested in animal models of
      autoimmune inflammatory diseases, such as ulcerative colitis and crescentic
      glomerulonephritis. We recently found that UTI has a neuroprotective effect on
      EAE by reducing oligodendrocyte apoptosis and demyelination. The anti
      inflammatory effects of UTI on EAE/MS, however, have never been investigated. We
      have therefore evaluated the anti-inflammatory effects of UTI in EAE and explored
      the mechanisms underlying this effect. EAE was induced in mice with and without
      UTI treatment. Inflammation and demyelination of spinal cords were evaluated by
      staining with hematoxylin and eosin and with Luxol fast blue, respectively.
      Inflammatory markers in serum were analyzed by the Luminex method, and spinal
      cords were evaluated by immunofluorescence and Western blotting. UTI
      significantly lowered the clinical and pathological scores and the serum
      concentrations of the inflammatory cytokines interleukin (IL)-1beta, IL-6, and
      matrix metal protease-9 (MMP-9). UTI also reduced the expression of tumor
      necrosis factor-alpha (TNF-alpha)/nuclear factor kappaB (NF-kappaB)/inducible
      nitric oxide synthase (iNOS) proteins and decreased CD11b(+) cells in spinal cord
      lesions. UTI may protect against EAE in mice by suppressing inflammatory
      responses. We think that UTI might be a potential therapeutic agent for MS. 

PMID- 24274997
TI  - Improving somatic health in severe mental illness.

PMID- 24274998
TI  - Long-term changes in heart rate variability in elementary school-aged children
      with sleep-disordered breathing.
AB  - OBJECTIVE: Sleep-disordered breathing (SDB) in adults and children has been
      associated with reduced heart rate variability (HRV) indicative of autonomic
      dysfunction, which in turn is associated with an increased risk for
      cardiovascular morbidity. However, the long-term effects of pediatric SDB that
      has either resolved or remains unresolved on HRV are unknown. METHODS: Forty
      Children with previously diagnosed SDB and 20 non snoring controls underwent
      repeat overnight polysomnography (PSG) four years after the original diagnosis.
      At follow-up, children aged 11 to 16 years were categorized into resolved
      (absence of snoring and obstructive apnea hypopnea index [OAHI]<=1) or unresolved
      (continued to snore or had an OAHI>1) groups. HRV was assessed using power
      spectral analysis for each sleep stage. RESULTS: There were no group differences
      in age, sex or body mass index (BMI) z score. Both the resolved and unresolved
      SDB groups showed significant improvement in OAHI. The control, resolved, and
      unresolved groups all showed a significant reduction in total power (P<.001), low
      frequency (LF) power (P<.05), high-frequency (HF) power (P<.001), and an increase
      in the LF/HF ratio (P<.001) from baseline to follow-up in all sleep stages.
      CONCLUSIONS: HRV did not differ between non snoring children and children with
      resolved and unresolved SDB four years after initial diagnosis, concomitant with
      a significant reduction in OAHI in both SDB groups. All groups demonstrated a
      decrease in HRV from baseline to follow-up which may reflect an age-related
      phenomenon in these children.

PMID- 24274999
TI  - Unhealthy lifestyle in early psychoses: the role of life stress and the
      hypothalamic-pituitary-adrenal axis.
AB  - An unhealthy lifestyle is thought to contribute to the metabolic syndrome in
      subjects with psychoses. In the present study we aimed to study whether life
      stress or cortisol measures may influence dietary patterns in subjects with early
      stages of psychoses. We studied 81 subjects with early psychoses (65 subjects
      with a psychotic disorder [PD] and <5 years of illness; 16 subjects at risk for
      psychosis [high-risk, HR]) and a control group of 25 healthy subjects (HS).
      Dietary habits were examined by a dietician, who registered food intake (24h
      recall). Physical activity was assessed by validated questionnaire. Life stress
      was assessed with Holmes-Rahe Social Readjustment Scale. Fasting morning salivary
      and plasma cortisol levels were determined. We found that PD and HR reported an
      unhealthier lifestyle with more smoking, reduced physical activity and poorer
      dietary habits. HR reported increased intake of calories and saturated fatty
      acids and reduced protein consumption, when compared to HS. Life stress was a
      predictor of these adverse behaviours, although we found opposite associations in
      HR and PD. Life stress was associated with increased intake of refined sugar in
      PD and decreased intake in HR and HS. Salivary cortisol was related to increased
      intake of saturated fat only in HR subjects, but cortisol levels in plasma or
      saliva were not associated with other dietary habits or obesity measures (BMI,
      waist circumference). Our study suggests that unhealthy diet in early psychoses
      is influenced by stress, but our data do not support this effect being mediated
      by hypercortisolism. Future preventive interventions in psychosis may target
      dietary habits, particularly for those who are at risk for psychosis. 

PMID- 24275000
TI  - In touch with your emotions: oxytocin and touch change social impressions while
      others' facial expressions can alter touch.
AB  - Interpersonal touch is frequently used for communicating emotions, strengthen
      social bonds and to give others pleasure. The neuropeptide oxytocin increases
      social interest, improves recognition of others' emotions, and it is released
      during touch. Here, we investigated how oxytocin and gentle human touch affect
      social impressions of others, and vice versa, how others' facial expressions and
      oxytocin affect touch experience. In a placebo-controlled crossover study using
      intranasal oxytocin, 40 healthy volunteers viewed faces with different facial
      expressions along with concomitant gentle human touch or control machine touch,
      while pupil diameter was monitored. After each stimulus pair, participants rated
      the perceived friendliness and attractiveness of the faces, perceived facial
      expression, or pleasantness and intensity of the touch. After intranasal oxytocin
      treatment, gentle human touch had a sharpening effect on social evaluations of
      others relative to machine touch, such that frowning faces were rated as less
      friendly and attractive, whereas smiling faces were rated as more friendly and
      attractive. Conversely, smiling faces increased, whereas frowning faces reduced,
      pleasantness of concomitant touch - the latter effect being stronger for human
      touch. Oxytocin did not alter touch pleasantness. Pupillary responses, a measure
      of attentional allocation, were larger to human touch than to equally intense
      machine touch, especially when paired with a smiling face. Overall, our results
      point to mechanisms important for human affiliation and social bond formation. 

PMID- 24275001
TI  - Recent and long-term occupational noise exposure and salivary cortisol level.
AB  - Environmental and occupational noise exposure have been related to increased risk
      of cardiovascular disease, hypothetically mediated by stress-activation of the
      hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to
      investigate the relation between recent and long-term occupational noise exposure
      and cortisol level measured off work to assess a possible sustained HPA-axis
      effect. We included 501 industrial, finance, and service workers who were
      followed for 24h during work, leisure, and sleep. Ambient occupational noise
      exposure levels were recorded every 5s by personal dosimeters and we calculated
      the full-shift LAEq value and estimated duration and cumulative exposure based on
      their work histories since 1980. For 332 workers who kept a log-book on the use
      of hearing protection devices (HPD), we subtracted 10 dB from every noise
      recording obtained during HPD use and estimated the noise level at the ear.
      Salivary cortisol concentration was measured at 20.00 h, the following day at
      awakening, and 30 min after awakening on average 5, 14 and 14.5h after finishing
      work. The mean ambient noise exposure level was 79.9 dB(A) [range: 55.0-98.9] and
      the mean estimated level at the ear 77.7 dB(A) [range: 55.0-94.2]. In linear and
      mixed regression models that adjusted for age, sex, current smoking, heavy
      alcohol consumption, personal income, BMI, leisure-time noise exposure level,
      time since occupational noise exposure ceased, awakening time, and time of saliva
      sampling, we observed no statistically significant exposure response relation
      between recent, or long-term ambient occupational noise exposure level and any
      cortisol parameter off work. This was neither the case for recent noise level at
      the ear. To conclude, neither recent nor long-term occupational noise exposure
      levels were associated with increased cortisol level off work. Thus, our results
      do not indicate that a sustained activation of the HPA axis, as measured by
      cortisol, is involved in the causal pathway between occupational noise exposure
      and cardiovascular disease.

PMID- 24275002
TI  - Decrease of serum S100B during an oral glucose tolerance test correlates
      inversely with the insulin response.
AB  - Increased S100B serum levels have been considered as a marker of glial pathology,
      brain damage, and blood-brain-barrier impairment. However, S100B expression has
      also been detected outside the nervous system, suggesting that altered S100B
      serum levels may not exclusively reflect brain-specific pathologies. Notably,
      S100B secretion in adipocytes seems to be down-regulated by insulin, and up
      regulated by stress and fasting. Therefore, we assumed that dynamic changes of
      S100B could be observed by challenging healthy subjects with an oral glucose
      tolerance test (OGTT). OGTT was performed in 17 healthy adult test persons (9
      male and 8 female). Apart from S100B, glucose, free fatty acids, insulin, C
      peptide, and cortisol were determined in all samples after an overnight fast (0
      h), as well as 1h and 2h after ingestion of 75 g glucose. Mean S100B
      concentrations decreased about 20% during the first hour after glucose ingestion
      (P<0.001). This decrease of S100B levels was not related to the declining morning
      peak of cortisol. However, the decrease of serum-S100B 1h after glucose ingestion
      correlated inversely with the respective changes of serum-insulin (r = -0.484,
      P=0.049) and serum-C-peptide (r = -0.570, P = 0.017). Our study suggests an
      inverse correlation between insulin secretion and S100B release after a
      standardized OGTT. Additional experiments, including the administration of
      insulin and the measurement of other food intake-related factors are important to
      ascertain an insulin-regulated S100B release in vivo. To improve comparability
      between clinical studies assessing conditions with rather mild changes of serum
      S100B, blood should be taken in a more standardized way (e.g., after fasting
      overnight).

PMID- 24275003
TI  - Early experience of a novel-environment in isolation primes a fearful phenotype
      characterized by persistent amygdala activation.
AB  - Prolonged maternal separation (MS) activates the neonate's hypothalamus-pituitary
      adrenal axis causing elevated basal and stress-induced corticosterone levels that
      may initiate amygdala-dependent fear learning. Here we test the hypothesis that
      the adult fearful phenotype is programmed by the pup's stressful experience
      during prolonged MS rather than by prolonged maternal absence per se. For this
      purpose, Wistar rat pups were exposed, on postnatal-day (pnd) 3, to: (i) repeated
      MS in home-environment (HOME-SEP), 8h-MS daily for three days with the pups
      remaining together in the home-cage; (ii) repeated-MS in a novel-environment
      (NOVEL-SEP), with the same separation procedure, but now the pups were
      individually housed in a novel-environment during the 8h dam's absence; (iii)
      repeated handling, which consisted of daily brief (15 min instead of 8h) MS in
      the home-altogether or in a novel-environment individually (HOME-HAN and NOVEL
      HAN, respectively); (iv) no-separation/no-handling (NON-SEP/NON-HAN) control
      condition, in which pups were left undisturbed in their home-cage. Compared to
      HOME-SEP rats, the NOVEL-SEP rats showed one day after the last MS enhanced
      stress-induced amygdala c-Fos expression and ACTH-release, despite of reduced
      adrenal corticosterone secretion. The higher amygdala c-Fos expression, ACTH
      release and reduced corticosterone output observed postnatally, persisted into
      adulthood of the NOVEL-SEP animals. Behaviorally, NOVEL-SEP juvenile rats
      displayed deficits in social play, had intact spatial memory in the peri-pubertal
      period and showed more contextual fear memory compared to HOME-SEP in adulthood.
      Finally, NOVEL-HAN, compared to HOME-HAN, displayed increased stress-induced
      corticosterone output, no deficits in social play and reduced contextual fear. In
      conclusion, programming of an adult fearful phenotype linked to amygdala priming
      develops if pups are repeatedly isolated from peers in a novel-environment, while
      away from the dam for a prolonged period of time.

PMID- 24275004
TI  - Salivary testosterone change following monetary wins and losses predicts future
      financial risk-taking.
AB  - While baseline testosterone has recently been implicated in risk-taking in men,
      less is known about the effects of changing levels of testosterone on financial
      risk. Here we attempt to influence testosterone in men by having them win or lose
      money in a chance-based competition against another male opponent. We employ two
      treatments where we vary the amount of money at stake so that we can directly
      compare winners to losers who earn the same amount, thereby abstracting from
      income effects. We find that men who experience a greater increase in bioactive
      testosterone take on more risk, an association that remains when controlling for
      whether the participant won the competition. In fact, whether subjects won the
      competition did not predict future risk. These results suggest that testosterone
      change, and thus individual differences in testosterone reactivity, rather than
      the act of winning or losing, influence financial risk-taking. 

PMID- 24275005
TI  - Transsexual patients' psychiatric comorbidity and positive effect of cross-sex
      hormonal treatment on mental health: results from a longitudinal study.
AB  - The aim of the present study was to evaluate the presence of psychiatric
      diseases/symptoms in transsexual patients and to compare psychiatric distress
      related to the hormonal intervention in a one year follow-up assessment. We
      investigated 118 patients before starting the hormonal therapy and after about 12
      months. We used the SCID-I to determine major mental disorders and functional
      impairment. We used the Zung Self-Rating Anxiety Scale (SAS) and the Zung Self
      Rating Depression Scale (SDS) for evaluating self-reported anxiety and
      depression. We used the Symptom Checklist 90-R (SCL-90-R) for assessing self
      reported global psychological symptoms. Seventeen patients (14%) had a DSM-IV-TR
      axis I psychiatric comorbidity. At enrollment the mean SAS score was above the
      normal range. The mean SDS and SCL-90-R scores were on the normal range except
      for SCL-90-R anxiety subscale. When treated, patients reported lower SAS, SDS and
      SCL-90-R scores, with statistically significant differences. Psychiatric distress
      and functional impairment were present in a significantly higher percentage of
      patients before starting the hormonal treatment than after 12 months (50% vs. 17%
      for anxiety; 42% vs. 23% for depression; 24% vs. 11% for psychological symptoms;
      23% vs. 10% for functional impairment). The results revealed that the majority of
      transsexual patients have no psychiatric comorbidity, suggesting that
      transsexualism is not necessarily associated with severe comorbid psychiatric
      findings. The condition, however, seemed to be associated with subthreshold
      anxiety/depression, psychological symptoms and functional impairment. Moreover,
      treated patients reported less psychiatric distress. Therefore, hormonal
      treatment seemed to have a positive effect on transsexual patients' mental
      health. 

PMID- 24275006
TI  - Oxytocin enhances attractiveness of unfamiliar female faces independent of the
      dopamine reward system.
AB  - Evidence from animal studies suggests that the social attraction and bonding
      effects of the neuropeptide oxytocin (OXT) are mediated by its modulation of
      dopamine (DA) release in brain reward centers, but this has not yet been
      demonstrated in humans. DA release can be measured by positron emission
      tomography (PET) using the radioligand [11C]raclopride. Its binding to DA D2
      receptors (D2R) is sensitive and reciprocally related to endogenous DA,
      especially in the striatum. In a randomized double-blind placebo-controlled
      within-subjects trial on 18 adult male volunteers we combined [11C]raclopride PET
      and a facial attractiveness rating task to establish whether intranasal OXT (24
      IU) increased both the perceived attractiveness of unfamiliar female faces and
      striatal DA release compared with placebo administration. While our behavioral
      data confirmed that subjects rated unfamiliar female faces as more attractive
      following OXT treatment, and this correlated with an increased perfusion rate in
      the striatum, there was no evidence for altered [11C]raclopride binding in the
      striatum or pallidum. Instead under OXT we rather observed an increased
      [11C]raclopride binding and reduced perfusion rate in subregions of the right
      dorsomedial prefrontal gyrus and superior parietal gyrus. The absence of OXT
      effects on dopamine release and D2 receptors in brain reward centers, despite
      increased striatal activity, implies that the peptide may facilitate perceived
      attraction via non-dopaminergic actions. 

PMID- 24275008
TI  - Effect of BDNF Val66Met polymorphism on regional white matter hyperintensities
      and cognitive function in elderly males without dementia.
AB  - White matter lesions, also termed White Matter Hyperintensities (WMH), on T2
      weighted MR images, are common in the elderly population. Of note, their presence
      is often accompanied with cognitive decline and the risk of dementia. Even though
      previous brain ischemia and WM lesion studies have been conducted and indicated
      that brain-derived neurotrophic factor (BDNF) might protect against neuronal cell
      death, the interaction between regional WMH volume and the BDNF Val66Met
      polymorphism on the cognitive performance of healthy elderly population remains
      unclear. To investigate the genetic effect of BDNF on cognitive function and
      regional WMH in the healthy elderly population, 90 elderly men, without dementia,
      with a mean age of 80.6 +/- 5.6 y/o were recruited to undergo cognitive tests,
      structural magnetic resonance imaging (MRI) scans, and genotyping of BDNF
      alleles. Compared with Met homozygotes, Val homozygotes showed significantly
      inferior short-term memory (STM) performance (P = .001). A tendency toward dose
      dependent effects of the Val allele on WMH volume was found, and Val homozygotes
      showed larger WMH volume in the temporal (P = .035), the occipital (P = .006),
      and the global WMH volume (P = .025) than others. Significant interaction effects
      of BDNF genotypes with temporal WMH volume on STM performance was observed (F1,89
      = 4.306, P = .041). Val homozygotes presented steeper negative correlation
      compared to Met carriers. Mediation analysis also demonstrated that WMH in
      temporal, limbic, and subcortical regions might mediate the relationship between
      BDNF's genetic effect and STM performance. Our findings supported the hypothesis
      that the BDNF Val66Met polymorphism may affect susceptibility to regional WMH
      volume and such genotype-by-WMH interaction effect is correlated with cognitive
      decline in non-demented elderly males, in which the Met allele plays a protective
      role.

PMID- 24275007
TI  - Linking plasma cortisol levels to phenotypic heterogeneity of posttraumatic
      stress symptomatology.
AB  - INTRODUCTION: Recent confirmatory factor analytic studies of the dimensional
      structure of posttraumatic stress disorder (PTSD) suggest that this disorder may
      be best characterized by five symptom dimensions-re-experiencing, avoidance,
      numbing, dysphoric arousal, and anxious arousal. Hypothalamic-pituitary-adrenal
      (HPA) axis dysregulation in PTSD and has been attributed to enhanced
      glucocorticoid responsiveness. However, little is known about how altered HPA
      axis function is related to this contemporary phenotypic model of PTSD. METHODS:
      We compared morning plasma cortisol levels of drug-free civilian adults with PTSD
      (N = 29) to trauma-exposed (TC; N = 12) and non-trauma-exposed healthy controls
      (HC; N = 23). We then examined the relation between cortisol levels and a
      contemporary 5-factor 'dysphoric arousal' model of PTSD symptoms among
      individuals with PTSD. RESULTS: After adjustment for white race/ethnicity,
      education, lifetime alcohol use disorder, and current smoking status, the PTSD
      (Cohen's d = 1.1) and TC (Cohen's d = 1.3) groups had significantly lower
      cortisol levels than the HC group; cortisol levels did not differ between the TC
      and PTSD groups. Except for age (r = -.46), none of the other demographic, trauma
      related, or clinical variables, including lifetime mood/anxiety disorder and
      severity of current depressive and anxiety symptoms, were associated with
      cortisol levels. In a stepwise linear regression analysis, age (beta = -.44) and
      severity of emotional numbing symptoms (beta = -.35) were independently
      associated with cortisol levels in the PTSD group; none of the other PTSD symptom
      clusters or depression symptoms were significant. Post hoc analyses revealed that
      severity of the emotional numbing symptom of restricted range of affect (i.e.,
      unable to have loving feelings) was independently related to cortisol levels
      (beta = -.35). CONCLUSION: These results suggest that trauma-exposed civilian
      adults with and without PTSD have significantly lower cortisol levels compared to
      healthy, non-trauma-exposed adults. They further suggest that low cortisol levels
      among adults with PTSD may be specifically linked to emotional numbing
      symptomatology that is unique to the PTSD phenotype and unrelated to depressive
      symptoms.

PMID- 24275009
TI  - Do depressed patients without activation of the hypothalamus-pituitary-adrenal
      (HPA) system have metabolic disturbances?
AB  - This study compared features of the metabolic syndrome between healthy controls
      and depressed patients without activation of the hypothalamus-pituitary-adrenal
      (HPA) system. After exclusion of non-suppressors to 1mg dexamethasone, we
      included 20 depressed inpatients and 34 healthy controls in the analyses. We
      assessed HPA system activity (diurnal saliva cortisol profile, cortisol
      excretion), normetanephrine excretion as well as fasting glucose, lipid profile
      and blood pressure. With regard to body composition, we measured waist
      circumference as well as visceral fat and adrenal volume by magnetic resonance
      (MR) imaging. Five depressed patients (25%) and five healthy controls (15%)
      fulfilled the criteria of the metabolic syndrome according NCEP-ATP-III.
      Depression was significantly related with fasting glucose and negatively
      associated with mean blood pressure (BP) and, by trend, with low HDL-cholesterol.
      We conclude that depressed patients may have modest metabolic disturbances even
      in the complete absence of activation of stress-responsive systems. Hence some
      metabolic disturbances in depressed patients may not be explicable by HPA
      activation. Additional factors are required to mediate the link between affective
      and metabolic disorders. 

PMID- 24275010
TI  - Acute stress-induced cortisol elevations mediate reward system activity during
      subconscious processing of sexual stimuli.
AB  - Stress is thought to alter motivational processes by increasing dopamine (DA)
      secretion in the brain's "reward system", and its key region, the nucleus
      accumbens (NAcc). However, stress studies using functional magnetic resonance
      imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc
      responsiveness toward reward cues. Results from both animal and human PET studies
      indicate that the stress hormone cortisol may be crucial in the interaction
      between stress and dopaminergic actions. In the present study we therefore
      investigated whether cortisol mediated the effect of stress on DA-related
      responses to -subliminal-presentation of reward cues using the Trier Social
      Stress Test (TSST), which is known to reliably enhance cortisol levels. Young
      healthy males (n = 37) were randomly assigned to the TSST or control condition.
      After stress induction, brain activation was assessed using fMRI during a
      backward-masking paradigm in which potentially rewarding (sexual), emotionally
      negative and neutral stimuli were presented subliminally, masked by pictures of
      inanimate objects. A region of interest analysis showed that stress decreased
      activation in the NAcc in response to masked sexual cues (voxel-corrected, p<05).
      Furthermore, with mediation analysis it was found that high cortisol levels were
      related to stronger NAcc activation, showing that cortisol acted as a suppressor
      variable in the negative relation between stress and NAcc activation. The present
      findings indicate that cortisol is crucially involved in the relation between
      stress and the responsiveness of the reward system. Although generally stress
      decreases activation in the NAcc in response to rewarding stimuli, high stress
      induced cortisol levels suppress this relation, and are associated with stronger
      NAcc activation. Individuals with a high cortisol response to stress might on one
      hand be protected against reductions in reward sensitivity, which has been linked
      to anhedonia and depression, but they may ultimately be more vulnerable to
      increased reward sensitivity, and addictions. Future studies investigating
      effects of stress on reward sensitivity should take into account the severity of
      the stressor and the individual cortisol response to stress.

PMID- 24275011
TI  - Brain region-specific methylation in the promoter of the murine oxytocin receptor
      gene is involved in its expression regulation.
AB  - Oxytocin is a nine amino acid neuropeptide that is known to play a critical role
      in fetal expulsion and breast-feeding, and has been recently implicated in
      mammalian social behavior. The actions of both central and peripheral oxytocin
      are mediated through the oxytocin receptor (Oxtr), which is encoded by a single
      gene. In contrast to the highly conserved expression of oxytocin in specific
      hypothalamic nuclei, the expression of its receptor in the brain is highly
      diverse among different mammalian species or even within individuals of the same
      species. The diversity in the pattern of brain Oxtr expression among mammals is
      thought to contribute to the broad range of social systems and organizations.
      Yet, the mechanisms underlying this diversity are poorly understood. DNA
      methylation is a major epigenetic mechanism that regulates gene transcription,
      and has been linked to reduced expression levels of the Oxtr in individuals with
      autism. Here we hypothesize that DNA methylation is involved in the expression
      regulation of Oxtr in the mouse brain. By combining bisulfite DNA conversion and
      Next-Generation Sequencing we found that specific CpG sites are differentially
      methylated between distinct brain regions expressing different levels of Oxtr
      mRNA. Some of these CpG sites are located within putative binding sites of
      transcription factors known to regulate Oxtr expression, including estrogen
      receptor alpha (ERalpha) and SP1. Specifically, methylation of the SP1 site was
      found to positively correlate with Oxtr expression. Furthermore, we revealed that
      the methylation levels of these sites in the various brain regions predict the
      relationship between ERalpha and Oxtr mRNA levels. Collectively, our results
      suggest that brain region-specific expression of the mouse Oxtr gene is
      epigenetically regulated by DNA methylation of its promoter. 

PMID- 24275012
TI  - Predictors of hair cortisol concentrations in older adults.
AB  - People at older ages are at increased risk for developing stress-related diseases
      associated with chronically elevated cortisol secretion. However, the main
      factors contributing to such endocrine alterations in this age group are still
      largely unknown. This cross-sectional study examined patterns of long-term
      integrated cortisol secretion, as assessed in hair, in a sample of 654
      participants in middle and old adulthood (mean age: 65.8 years; range: 47-82
      years) from the German cohort of the European Prospective Investigation into
      Cancer and Nutrition (EPIC) study in Potsdam. Hair cortisol concentrations (HCC)
      were determined from the first scalp-near 3 cm hair segment and several
      sociodemographic, lifestyle, anthropometric, disease-related, and psychological
      parameters were assessed. In simple linear regressions, HCC were found to
      increase with participants' age and to be higher in men compared to women. HCC
      also showed positive associations with waist-to-hip ratio, waist circumference,
      smoking, prevalent type 2 diabetes mellitus, mental health, daytime sleeping, and
      being unemployed or retired--as well as a negative association with diastolic
      blood pressure. After full mutual adjustment, only age and smoking remained
      independent predictors of HCC. The association between prevalent type 2 diabetes
      mellitus and HCC was attenuated but still persisted independently in women.
      Similar, a positive relationship between HCC and alcohol consumption was found in
      women. The current results confirm previous evidence of positive associations of
      HCC with age, sex, alcohol consumption, and type 2 diabetes mellitus and add new
      knowledge on factors--such as smoking--that may contribute to elevated cortisol
      levels in people at older ages.

PMID- 24275013
TI  - Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in
      depression.
AB  - BACKGROUND: In this study, the impact of quetiapine fumarate extended release
      (QXR) and escitalopram (ESC) on HPA axis activity was investigated in depressed
      patients in relationship to antidepressant efficacy. METHODS: In a randomized,
      open-label 5-week trial 60 inpatients suffering from major depression (DSM-IV
      criteria) were treated for 5 weeks with either QXR (300 mg/day) or ESC
      (10mg/day). The dexamethasone/CRH (DEX/CRH) test was performed before treatment,
      after 1, and after 5 weeks of treatment. Cortisol (COR) AUC values were used to
      assess HPA axis function. The Hamilton Depression Rating Scale was used weekly to
      estimate antidepressant efficacy. RESULTS: QXR and ESC showed comparable
      antidepressant effects but strongly differed in their impact on HPA axis
      activity. In the QXR group, a marked inhibition of COR AUC levels was observed
      which was most pronounced after one week of treatment but showed a partial re
      increase after 5 weeks of treatment. In contrast, ESC transiently stimulated COR
      AUC values (week 1) whereas COR AUC levels at week 0 and week 5 were comparable.
      COR improvement at week 1 (defined as COR peak value reduction between DEX/CRH
      test 1 and 2) was significantly associated with better clinical outcome.
      CONCLUSION: Apparently, different effects on HPA axis activity reflect distinct
      pharmacoendocrinological properties of psychotropic drugs.

PMID- 24275014
TI  - Social partners prevent alcohol relapse behavior in prairie voles.
AB  - There is robust evidence for a protective role of interpersonal factors such as
      social support on alcohol relapse, but research on the mechanisms that social
      factors may be acting on to effectively protect individuals against relapse is
      lacking. Prairie voles are highly social, monogamous rodents that freely self
      administer ethanol in high amounts, and are a useful model for understanding
      social influences on alcohol drinking. Here we investigated whether prairie voles
      can be used to model social influences on relapse using the alcohol deprivation
      effect, in which animals show a transient increase in ethanol drinking following
      deprivation. In Experiment I, subjects were housed alone during four weeks of 24
      h access to 10% ethanol in a two-bottle choice test. Ethanol was then removed
      from the cage for 72 h. Animals remained in isolation or were then housed with a
      familiar same-sex social partner, and ethanol access was resumed. Animals that
      remained isolated showed an increase in ethanol intake relative to pre
      deprivation baseline, indicative of relapse-like behavior. However, animals that
      were socially housed did not show an increase in ethanol intake, and this was
      independent of whether the social partner also had access to ethanol. Experiment
      II replicated the alcohol deprivation effect in a separate cohort of isolated
      animals. These findings demonstrate that prairie voles display an alcohol
      deprivation effect and suggest a 'social buffering' effect of relapse-like
      behavior in the prairie vole. This behavioral paradigm provides a novel approach
      for investigating the behavioral and neurobiological underpinnings of social
      influences on alcohol relapse.

PMID- 24275015
TI  - Nitric oxide as a regulatory molecule in the processing of the visual stimulus.
AB  - Nitric oxide (NO) is a highly reactive gas with considerable diffusion power that
      is produced pre- and post synaptically in the central nervous system (CNS). In
      the visual system, it is involved in the processing of the visual information
      from the retina to superior visual centers. In this review we discuss the main
      mechanisms through which nitric oxide acts, in physiological levels, on the
      retina, lateral geniculate nucleus (LGN) and primary visual cortex. In the
      retina, the cGMP-dependent nitric oxide activity initially amplifies the signal,
      subsequently increasing the inhibitory activity, suggesting that the signal is
      "filtered". In the thalamus, on dLGN, neuronal activity is amplified by NO
      derived from brainstem cholinergic cells, in a cGMP-independent mechanism; the
      result is the amplification of the signal arriving from retina. Finally, on the
      visual cortex (V1), NO acts through changes on the cGMP levels, increasing signal
      detection. These observations suggest that NO works like a filter, modulating the
      signal along the visual pathways. 

PMID- 24275016
TI  - A quantitative assessment of the total inward leakage of NaCl aerosol
      representing submicron-size bioaerosol through N95 filtering facepiece
      respirators and surgical masks.
AB  - Respiratory protection provided by a particulate respirator is a function of
      particle penetration through filter media and through faceseal leakage. Faceseal
      leakage largely contributes to the penetration of particles through a respirator
      and compromises protection. When faceseal leaks arise, filter penetration is
      assumed to be negligible. The contribution of filter penetration and faceseal
      leakage to total inward leakage (TIL) of submicron-size bioaerosols is not well
      studied. To address this issue, TIL values for two N95 filtering facepiece
      respirator (FFR) models and two surgical mask (SM) models sealed to a manikin
      were measured at 8 L and 40 L breathing minute volumes with different artificial
      leak sizes. TIL values for different size (20-800 nm, electrical mobility
      diameter) NaCl particles representing submicron-size bioaerosols were measured
      using a scanning mobility particle sizer. Efficiency of filtering devices was
      assessed by measuring the penetration against NaCl aerosol similar to the method
      used for NIOSH particulate filter certification. Results showed that the most
      penetrating particle size (MPPS) was ~45 nm for both N95 FFR models and one of
      the two SM models, and ~350 nm for the other SM model at sealed condition with no
      leaks as well as with different leak sizes. TIL values increased with increasing
      leak sizes and breathing minute volumes. Relatively, higher efficiency N95 and SM
      models showed lower TIL values. Filter efficiency of FFRs and SMs influenced the
      TIL at different flow rates and leak sizes. Overall, the data indicate that good
      fitting higher-efficiency FFRs may offer higher protection against submicron-size
      bioaerosols. 

PMID- 24275018
TI  - A model for a spatially structured metapopulation accounting for within patch
      dynamics.
AB  - We develop a stochastic metapopulation model that accounts for spatial structure
      as well as within patch dynamics. Using a deterministic approximation derived
      from a functional law of large numbers, we develop conditions for extinction and
      persistence of the metapopulation in terms of the birth, death and migration
      parameters. Interestingly, we observe the Allee effect in a metapopulation
      comprising two patches of greatly different sizes, despite there being decreasing
      patch specific per-capita birth rates. We show that the Allee effect is due to
      the way the migration rates depend on the population density of the patches. 

PMID- 24275017
TI  - Guideline-adherent therapy in patients with cardiovascular diseases in Taiwan.
AB  - BACKGROUND/PURPOSE: Aggressive and persistent control of risk factors is
      recommended for prevention of secondary comorbidities in patients with
      cardiovascular diseases. This study aimed to evaluate guideline recommendations
      for achieving targets for lipid and blood pressure (BP) control in patients with
      cardiovascular diseases in Taiwan. METHODS: This multicenter cohort study was
      conducted in 14 hospitals in Taiwan. A total of 3316 outpatients who had
      established cerebrovascular disease (CVD), coronary artery disease (CAD), or both
      were recruited. Risk factors for comorbid conditions such as high BP, sugar,
      hemoglobin A1C, abnormal lipids, lipoproteins, and medication use were compared
      between patients with CVD, CAD, or both. RESULTS: Of all patients, 503 (15.2%)
      had CVD only, 2568 (77.4%) had CAD only, and 245 (7.4%) had both CVD and CAD.
      Compared with patients who had only CAD, those with CVD were older, had higher
      frequency of hypertension, and lower frequency of diabetes mellitus. Patients
      with CAD were more likely to receive lipid-lowering and antihypertensive drugs
      than those with CVD (p < 0.001). Only 54.8% and 55.9% of patients achieved the
      recommended lipid and BP control targets, respectively. Patients with CVD
      (adjusted odds ratio: 0.61; 95% confidence interval: 0.48-0.78; p < 0.001) and
      women (adjusted odds ratio: 0.65; 95% confidence interval: 0.55-0.78; p < 0.001)
      were less likely to achieve the recommended lipid and BP targets. CONCLUSION: The
      guideline-recommended targets for lipids and BP in patients with CAD and CVD were
      still suboptimal in Taiwan. Greater efforts are required to achieve the targets,
      particularly in patients with CVD and in women.

PMID- 24275019
TI  - In situ measurement of superoxide and hydroxyl radicals by frequency mixing
      detection technique.
AB  - Frequency mixing magnetic detection (FMMD) was used to detect superoxide from
      hypoxanthine and xanthine reaction and to detect hydroxyl radical from the Fenton
      reaction. FMMD was also applied to measure the reactive oxygen species (ROS)
      level released from microglial cells. We could assess the formation and
      extinction of the free radicals without a spin trap reagent. The FMMD signal
      amplitude scaled with the concentration of the radicals. It was verified that no
      signals are obtained from the substrates and reagents. Based on the observations
      and on previous research, we suggest that the FMMD signals originate from
      superoxide and hydroxyl radicals, indicating that FMMD can be used to detect O
      centered radicals. Subsequent analysis of free radicals generated from living
      microglial cells showed that there were significant differences between the
      activated microglial cells and resting ones. The results of this research are
      promising regarding the applications of FMMD for in situ measurement of free
      radicals from various sources, including the cell. 

PMID- 24275020
TI  - Understanding the gap between cognitive abilities and daily living skills in
      adolescents with autism spectrum disorders with average intelligence.
AB  - Daily living skills standard scores on the Vineland Adaptive Behavior Scales-2nd
      edition were examined in 417 adolescents from the Simons Simplex Collection. All
      participants had at least average intelligence and a diagnosis of autism spectrum
      disorder. Descriptive statistics and binary logistic regressions were used to
      examine the prevalence and predictors of a "daily living skills deficit," defined
      as below average daily living skills in the context of average intelligence
      quotient. Approximately half of the adolescents were identified as having a daily
      living skills deficit. Autism symptomatology, intelligence quotient, maternal
      education, age, and sex accounted for only 10% of the variance in predicting a
      daily living skills deficit. Identifying factors associated with better or worse
      daily living skills may help shed light on the variability in adult outcome in
      individuals with autism spectrum disorder with average intelligence. 

PMID- 24275021
TI  - Integrating multimodal transport into cellulosic biofuel supply chain design
      under feedstock seasonality with a case study based on California.
AB  - A multistage, mixed integer programing model was developed that fully integrates
      multimodal transport into the cellulosic biofuel supply chain design under
      feedstock seasonality. Three transport modes are considered: truck, single
      railcar, and unit train. The goal is to minimize the total cost for
      infrastructure, feedstock harvesting, biofuel production, and transportation.
      Strategic decisions including the locations and capacities of transshipment hubs,
      biorefineries, and terminals and tactical decisions on system operations are
      optimized in an integrated manner. When the model was implemented to a case study
      of cellulosic ethanol production in California, it was found that trucks are
      convenient for short-haul deliveries while rails are more effective for long-haul
      transportation. Taking the advantage of these benefits, the multimodal transport
      provides more cost effective solutions than the single-mode transport (truck). 

PMID- 24275022
TI  - Potential of bioethanol production from olive mill solid wastes.
AB  - The main objective of this study was to screen endogenous microorganisms grown on
      olive mill solid wastes (OMSW) with the potential to ferment pentoses and produce
      ethanol. Two yeasts were isolated and identified as Issatchenkia orientalis, and
      Pichia galeiformis/manshurica. The adaptation of the strains displayed a positive
      impact on the fermentation process. In terms of xylose utilization and ethanol
      production, all strains were able to utilize xylose and produce xylitol but no
      ethanol was detected. Separate hydrolysis and fermentation process on hydrolysate
      undergo detoxification, strain I. orientalis showed the best efficiency in
      producing of ethanol when supplemented with glucose. Using simultaneous
      saccharification and fermentation process following pretreatment of OMSW, the
      average ethanol yield was 3 g/100 g dry OMSW. Bioethanol production from OMSW is
      not economic despite the raw material is cheap.

PMID- 24275023
TI  - Specific lignin precipitation for oligosaccharides recovery from hot water wood
      extract.
AB  - Hot water extraction is an important strategy of wood fractionation, by which the
      hemicelluloses can be separated for value-added products, while the residual
      solid can still be processed into traditional wood products. In this study, a
      combined process consisting of specific lignin precipitation and dialysis was
      proposed to recover hemicellulosic oligosaccharides (OS) from hot water extract
      (HWE). The results showed that polyaluminium chloride (PAC) precipitation was
      highly specific to large molecular lignin, leading to 25.1% lignin removal with
      negligible OS loss through charge neutralization mechanism. The separation was
      further enhanced by dialysis, reaching 37.6% OS recovery from HWE with remarkable
      purity of 94.1%. By the proposed process, 56.36 g OS, mainly xylooligosaccharides
      with two fractions of 5.2 and 0.51 kDa was recovered from one kg dried wood. This
      process can be envisaged as a great contribution to wood biorefinery.

PMID- 24275024
TI  - Probing the nature of AFEX-pretreated corn stover derived decomposition products
      that inhibit cellulase activity.
AB  - Sequential fractionation of AFEX-pretreated corn stover extracts was carried out
      using ultra-centrifugation, ultra-filtration, and solid phase extraction to
      isolate various classes of pretreatment products to evaluate their inhibitory
      effect on cellulases. Ultra-centrifugation removed dark brown precipitates that
      caused no appreciable enzyme inhibition. Ultra-filtration of ultra-centrifuged
      AFEX-pretreated corn stover extractives using a 10 kDa molecular weight cutoff
      (MWCO) membrane removed additional high molecular weight components that
      accounted for 24-28% of the total observed enzyme inhibition while a 3 kDa MWCO
      membrane removed 60-65%, suggesting significant inhibition is caused by
      oligomeric materials. Solid phase extraction (SPE) of AFEX-pretreated corn stover
      extractives after ultra-centrifugation removed 34-43% of the inhibition; ultra
      filtration with a 5 kDa membrane removed 44-56% of the inhibition and when this
      ultra-filtrate was subjected to SPE a total of 69-70% of the inhibition were
      removed. Mass spectrometry found several phenolic compounds among the hydrophobic
      inhibition removed by SPE adsorption.

PMID- 24275025
TI  - Treating refinery wastewaters in microbial fuel cells using separator electrode
      assembly or spaced electrode configurations.
AB  - The effectiveness of refinery wastewater (RW) treatment using air-cathode,
      microbial fuel cells (MFCs) was examined relative to previous tests based on
      completely anaerobic microbial electrolysis cells (MECs). MFCs were configured
      with separator electrode assembly (SEA) or spaced electrode (SPA) configurations
      to measure power production and relative impacts of oxygen crossover on organics
      removal. The SEA configuration produced a higher maximum power density (280+/-6
      mW/m(2); 16.3+/-0.4 W/m(3)) than the SPA arrangement (255+/-2 mW/m(2)) due to
      lower internal resistance. Power production in both configurations was lower than
      that obtained with the domestic wastewater (positive control) due to less
      favorable (more positive) anode potentials, indicating poorer biodegradability of
      the RW. MFCs with RW achieved up to 84% total COD removal, 73% soluble COD
      removal and 92% HBOD removal. These removals were higher than those previously
      obtained in mini-MEC tests, as oxygen crossover from the cathode enhanced
      degradation in MFCs compared to MECs.

PMID- 24275026
TI  - Multiple imputation in the presence of high-dimensional data.
AB  - Missing data are frequently encountered in biomedical, epidemiologic and social
      research. It is well known that a naive analysis without adequate handling of
      missing data may lead to bias and/or loss of efficiency. Partly due to its ease
      of use, multiple imputation has become increasingly popular in practice for
      handling missing data. However, it is unclear what is the best strategy to
      conduct multiple imputation in the presence of high-dimensional data. To answer
      this question, we investigate several approaches of using regularized regression
      and Bayesian lasso regression to impute missing values in the presence of high
      dimensional data. We compare the performance of these methods through numerical
      studies, in which we also evaluate the impact of the dimension of the data, the
      size of the true active set for imputation, and the strength of correlation. Our
      numerical studies show that in the presence of high-dimensional data the standard
      multiple imputation approach performs poorly and the imputation approach using
      Bayesian lasso regression achieves, in most cases, better performance than the
      other imputation methods including the standard imputation approach using the
      correctly specified imputation model. Our results suggest that Bayesian lasso
      regression and its extensions are better suited for multiple imputation in the
      presence of high-dimensional data than the other regression methods.

PMID- 24275027
TI  - Self-reported adverse events in adolescents aged 13-18 years after mass
      vaccination with pertussis-containing vaccine, following a school outbreak.

PMID- 24275028
TI  - An exploration of artists' perspectives of participatory arts and health projects
      for people with mental health needs.
AB  - OBJECTIVES: This study addresses the views and experiences of artists who run
      participatory arts and health courses for those with mental health or social
      problems. STUDY DESIGN: Qualitative research with 11 artists from three different
      organizations providing participatory arts and health courses. METHODS: Semi
      structured in-depth interviews were conducted. Participants provided oral
      contributions that were transcribed and then thematically analysed by the
      authors. RESULTS: Participants described perceived positive benefits of
      participatory arts and health courses, including developing friendships, self
      expression and creativity, a non-judgmental environment, along with key issues
      arising, including managing challenging behaviours and provision of follow-on
      options. CONCLUSIONS: Results indicate that improvements in well-being can be
      identified by artists during courses, the activity can help develop friendships,
      courses can be well managed in community settings, and benefits of follow-on
      activities should be investigated in future.

PMID- 24275029
TI  - Trends in overweight and obesity among rural preschool children in southeast
      China from 1998 to 2005.
AB  - OBJECTIVE: To examine the trends in prevalence of overweight and obesity, as well
      as the impact of stunting on overweight/obesity, among rural children aged <60
      months in southeast China between 1998 and 2005. STUDY DESIGN: Data from the
      population-based Child Health Care Surveillance System (CHCSS) from eight
      counties in southeast China were used. Overweight and obesity were defined as
      weight-for-height/length z score >2 and >3 standard deviations (SDs),
      respectively, and stunting was defined as height/length-for-age z score <-2 SD,
      in accordance with the 2006 World Health Organization growth standard. METHODS: A
      total of 550,693 clinic visit records of 280,931 children from the CHCSS,
      collected between 1998 and 2005, were included in the analysis. The age- and sex
      adjusted prevalence rates of overweight, obesity and stunting were estimated for
      each year, and the trends over time were examined. The impact of stunting on
      overweight/obesity was determined using multiple logistic regression analysis.
      RESULTS: The prevalence of overweight increased from 3.7% in 1998 to 3.9% in 2005
      (P < 0.001), but no increase in the prevalence of obesity was observed (0.5% in
      1998 and 0.6% in 2005; P > 0.05). The prevalence of obesity increased
      significantly in 2005 compared with 1998 among boys aged >=24 months, but was
      similar between 1998 and 2005 for girls aged >=12 months. The prevalence of
      stunting decreased from 3.9% in 1998 to 1.6% in 2005 (P < 0.001). There was a
      positive association between stunting and overweight/obesity in both 1998 and
      2005, although the association was attenuated in 2005. CONCLUSION: There was a
      small increase in the prevalence of overweight among rural preschool children in
      southeast China from 1998 to 2005. The prevalence of obesity remained stable.
      However, the prevalence of stunting decreased and its positive influence on
      overweight/obesity was weaker in 2005.

PMID- 24275030
TI  - An even more beautiful game.

PMID- 24275031
TI  - Health behaviours and mental health status of parents with intellectual
      disabilities: cross sectional study.
AB  - OBJECTIVES: The authors sought to: (1) estimate the prevalence of health
      behaviours, mental health and exposure to social determinants of poorer health
      among parents with and without intellectual disability; and (2) determine the
      extent to which between-group differences in health behaviours/status may be
      attributable to differential exposure to social determinants of poorer health.
      STUDY DESIGN: Cross sectional survey. METHODS: Secondary analysis of
      confidentialized needs analysis data collected in three Primary Care Trusts in
      England on 46,023 households with young children. RESULTS: Households containing
      a parent with intellectual disabilities are at increased risk of: (1) poorer
      parental mental health, parental drug and alcohol abuse and smoking; (2) exposure
      to a range of environmental adversities. Controlling for the latter eliminated
      the increased risk of poorer health for single parent households headed by a
      person with intellectual disabilities. For two parent headed households, risk of
      poorer parental mental health remained elevated. CONCLUSIONS: The poorer health
      of parents with intellectual disability may be accounted for by their markedly
      greater risk of exposure to common social determinants of poorer health rather
      than being directly attributable to their intellectual disability.

PMID- 24275032
TI  - Screening and brief intervention for substance misuse in Thailand.

PMID- 24275033
TI  - Assessing the effects of HIV/AIDS and TB disease control programmes on health
      systems in low- and middle-income countries of Southeast Asia: a semi-systematic
      review of the literature.
AB  - OBJECTIVE: To systematically review the literature on if and how HIV/AIDS and TB
      programmes have impacted on general healthcare systems in Association of
      Southeast Asian Nations (ASEAN) countries. METHODS: Medline, Embase, Global
      Health and CINHAL were searched for English language literature published between
      1st January 2003 and 31st March 2011. Papers included had to focus on: HIV and/or
      TB control programmes; the low- and-middle-income ASEAN countries; and factors
      related to any health systems functions. The effects were examined along six
      system functions: Stewardship and Governance; Financing; Planning; Service
      Delivery; Monitoring and Evaluation; and Demand Generation. A comprehensive
      thematic analytical tool aligned with the above six health systems functions was
      developed to support data extraction and analysis. FINDINGS: 88 papers met the
      inclusion criteria. Most programme effects highlighted were related with health
      service delivery. The other five health system functions were seldom scrutinized,
      and each covered by less than a quarter of papers. Overall 69% of effects
      highlighted were positive effects whereas 31% were negative. CONCLUSION: There
      was a paucity of robust evidence. Effects on health systems were rarely a focus
      of research protocols but more often a minor component in the Results/Discussion
      sections. Particular attention should be paid by Global Health Initiatives to the
      negative effects that emerged from this study, such as the development of
      parallel systems, specific incentives not available to the general health
      systems, and lack of integration of services with private healthcare providers.

PMID- 24275034
TI  - Adult obesity prescribing in Wiltshire.

PMID- 24275036
TI  - Getting to zero.

PMID- 24275035
TI  - Variation in U.S. traffic safety policy environments and motor vehicle fatalities
      1980-2010.
AB  - OBJECTIVE: To examine the impact of variation in state laws governing traffic
      safety on motor vehicle fatalities. STUDY DESIGN: Repeated cross sectional time
      series design. METHODS: Fixed effects regression models estimate the relationship
      between state motor vehicle fatality rates and the strength of the state law
      environment for 50 states, 1980-2010. The strength of the state policy
      environment is measured by calculating the proportion of a set of 27 evidence
      based laws in place each year. The effect of alcohol consumption on motor vehicle
      fatalities is estimated using a subset of alcohol laws as instrumental variables.
      RESULTS: Once other risk factors are controlled in statistical models, states
      with stronger regulation of safer driving and driver/passenger protections had
      significantly lower motor vehicle fatality rates for all ages. Alcohol
      consumption was strongly associated with higher MVC death rates, as were state
      unemployment rates. CONCLUSIONS: Encouraging laggard states to adopt the full
      range of available laws could significantly reduce preventable traffic-related
      deaths in the U.S. - especially those among younger individuals. Estimating the
      relationship between different policy environments and health outcomes can
      quantify the result of policy gaps.

PMID- 24275037
TI  - Patients' expectations and online presence of Oral and Maxillofacial Surgery in
      the United Kingdom.
AB  - In patient-centred medical practice, consideration of the patients' expectations
      is vital to the planning and delivery of service. Modern medicine must use the
      continuing advances in information technology to disseminate knowledge and raise
      awareness among patients and the public. People increasingly use the Internet to
      search for information on health, and the online presence of an organisation or a
      profession is known to bring a wide range of benefits. We aimed to find out what
      patients expect from the website of an Oral and Maxillofacial Surgery (OMFS) unit
      and to assess the online presence of OMFS units in the United Kingdom. Results
      from 100 self-administered questionnaires showed that there were 18 common
      domains that patients would like to see on OMFS websites. When ranked according
      to the number of times they were mentioned, a map of the department was mentioned
      most and the complaints policy least. Of the 156 OMFS units in the UK, only 51%
      have websites and of these, 80% are in London. There were none in Wales and
      Northern Ireland. Only half of the websites contained information that related to
      patients' expectations. Strategies to improve the content of websites for OMFS
      units and to improve their online presence are urgently needed. 

PMID- 24275038
TI  - Mitotic phosphorylation of histone H3 threonine 80.
AB  - The onset and regulation of mitosis is dependent on phosphorylation of a wide
      array of proteins. Among the proteins that are phosphorylated during mitosis is
      histone H3, which is heavily phosphorylated on its N-terminal tail. In addition,
      large-scale mass spectrometry screens have revealed that histone H3
      phosphorylation can occur at multiple sites within its globular domain, yet
      detailed analyses of the functions of these phosphorylations are lacking. Here,
      we explore one such histone H3 phosphorylation site, threonine 80 (H3T80), which
      is located on the nucleosome surface. Phosphorylated H3T80 (H3T80ph) is enriched
      in metazoan cells undergoing mitosis. Unlike H3S10 and H3S28, H3T80 is not
      phosphorylated by the Aurora B kinase. Further, mutations of T80 to either
      glutamic acid, a phosphomimetic, or to alanine, an unmodifiable residue, result
      in an increase in cells in prophase and an increase in anaphase/telophase
      bridges, respectively. SILAC-coupled mass spectrometry shows that phosphorylated
      H3T80 (H3T80ph) preferentially interacts with histones H2A and H4 relative to non
      phosphorylated H3T80, and this result is supported by increased binding of
      H3T80ph to histone octamers in vitro. These findings support a model where
      H3T80ph, protruding from the nucleosome surface, promotes interactions between
      adjacent nucleosomes to promote chromatin compaction during mitosis in metazoan
      cells. 

PMID- 24275039
TI  - Organic barn dust extract exposure impairs porcine macrophage function in vitro:
      implications for respiratory health.
AB  - Respiratory diseases are responsible for a significant amount of animal morbidity
      and mortality in the swine industry, including the majority of nursery and
      grower/finisher deaths. Innate immunity, including the maintenance of lung
      macrophage health and function, is an important defense mechanism against
      respiratory pathogens and their associated losses. Chronic exposure of swine
      industry workers to airborne barn dust results in significant predisposition to
      airway diseases and impairment of alveolar macrophage (AMphi) function. Because
      of their importance in maintaining normal respiratory function, this study was
      designed to evaluate the impact of barn dust on swine macrophages. As measures of
      macrophage function, we evaluated the activation of NF-kappaB, cytokine
      production, cell surface marker expression and the phagocytic and antibacterial
      capabilities of porcine macrophages after in vitro exposure to an organic swine
      barn dust extract (ODE). ODE treatment induced AMphi secretion of both pro- and
      anti-inflammatory cytokines, suggesting a complex activation profile.
      Additionally, ODE induced expression of genes (TLR2, NOD2) involved in sensing
      Gram-positive bacteria, a major component of barn dust. ODE exposure also
      enhanced the expression of several cell surface markers of activation, including
      a receptor for the porcine reproductive and respiratory syndrome virus. Moreover,
      two key functions of AMphi, phagocytosis and bacterial killing, were impaired
      after exposure to ODE. Treatment with ODE for the first 72 h of differentiation
      also inhibited the ability of monocyte-derived macrophages to translocate NF
      kappaB to the nucleus following endotoxin stimulation. Taken together, these
      results demonstrate, for the first time, that organic dust extract exposure
      negatively affects pig macrophage activation and function, potentially enhancing
      host susceptibility to a variety of respiratory infections.

PMID- 24275040
TI  - Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to
      virulent Trypanosoma cruzi.
AB  - Chagas' disease, endemic in Latin America, is spread in natural environments
      through animal reservoirs, including marsupials, mice and guinea pigs. Farms
      breeding guinea pigs for food are located in some Latin-American countries with
      consequent risk of digestive infection. The aim of this work was to study the
      effect of vaccination with Trypanosoma rangeli in guinea pigs challenged with
      Trypanosoma cruzi. Animals were vaccinated with fixated epimastigotes of T.
      rangeli, emulsified with saponin. Controls received only PBS. Before being
      challenged with T. cruzi, parasitemia, survival rates and histological studies
      were performed. The vaccinated guinea pigs revealed significantly lower
      parasitemia than controls (p<0.0001-0.01) and a discrete lymphomonocytic
      infiltrate in cardiac and skeletal muscles was present. In the chronic phase, the
      histological view was normal. In contrast, control group revealed amastigote
      nests and typical histopathological alterations compatible with chagasic
      myocarditis, endocarditis and pericarditis. These results, together with previous
      works in our laboratory, show that T. rangeli induces immunoprotection in three
      species of animals: mice, guinea pigs and dogs. The development of vaccines for
      use in animals, like domestic dogs and guinea pigs in captivity, opens up new
      opportunities for preventive tools, and could reduce the risk of infection with
      T. cruzi in the community. 

PMID- 24275041
TI  - Interscapulothoracic (forequarter) amputation for malignant tumors involving the
      upper extremity: surgical technique and case series.
AB  - BACKGROUND: Forequarter amputation (FQA) is reserved for large, multifocal, or
      recurrent tumors affecting the shoulder and upper extremity. Although it is
      performed less frequently with the advancement of limb salvage surgery, FQA
      remains an important treatment in select patients. The purpose of this study is
      to illustrate the surgical technique in a case series of 4 patients. METHODS:
      Between 2010 and 2012, 4 patients (mean age, 61 years; range, 36-78 years)
      presented with malignant disease of the upper extremity that was not amenable to
      or had failed limb salvage. All patients had FQA by the illustrated anterior
      clavicular osteotomy technique. Patient data were retrospectively reviewed from
      preoperative workup until last follow-up or death. RESULTS: All patients had
      tumors that involved major neurovascular structures of the upper extremity and
      shoulder girdle. One presented with neuroendocrine carcinoma and has achieved
      local control after FQA. Three presented with high-grade sarcoma. One of these
      had recurrence after prior limb salvage and neoadjuvant radiation and
      unfortunately succumbed to metastatic disease 6 months after FQA. An additional
      sarcoma patient who presented after shoulder arthroscopy for a "labral cyst" with
      recurrent and fulminant synovial sarcoma succumbed to her disease. The remaining
      sarcoma patient has had no recurrence and minimal phantom pain at last follow-up.
      DISCUSSION: Obtaining vascular control early in the procedure is crucial to
      minimize blood loss. When it is indicated, FQA is a relatively safe and reliable
      procedure for dealing with otherwise challenging tumors of the shoulder girdle
      and upper extremity. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

PMID- 24275042
TI  - Slow response to entecavir treatment in treatment-naive HBV patients is
      conditioned by immune response rather than by the presence or selection of
      refractory variants.
AB  - BACKGROUND: Entecavir is the drug of choice as first-line treatment for treatment
      naive HBV patients. As a result of the high genetic barrier to resistance,
      treatment failure remains rare, but occurs within 3 years of initiation,
      suggesting that viral genetic characteristics may provide a fast lane to
      resistance. One of the main concerns is the long time to viral suppression
      observed in some (even treatment-naive) patients. The reasons for this phenomenon
      were investigated in a group of chronic hepatitis B treatment-naive patients.
      METHODS: Out of 23 treatment-naive patients starting entecavir, the 5 with the
      best and those with the worst viral load decay curves were selected for the
      study. Quasispecies analysis was performed for the reverse
      transcriptase/hepatitis B surface antigen (HBsAg) open reading frame (ORF) by
      ultra-deep pyrosequencing. For each patient, the analysis was performed at
      baseline (T0) and when viraemia reached between 15,000 and 200 IU/ml (T1).
      RESULTS: The few resistance mutations present at T0 were not selected by
      treatment; no other resistance mutations or suggestive mutational patterns were
      selected at T1. Selective pressure analysis indicated that both at T0 and T1 the
      HBsAg ORF was subjected to a significantly higher pressure in rapid responders,
      especially in a region rich in cytotoxic T-lymphocyte (CTL) epitopes.
      CONCLUSIONS: The results did not provide evidence that a slower response to
      entecavir is due to the emergence of less sensitive variants. Rather, the lower
      selective pressure and variability in humoral and CTL epitopes in slow responders
      suggests that their immune response might be at odds in rapidly clearing infected
      cells from the liver.

PMID- 24275043
TI  - Cerebral oximetry and cerebral blood flow monitoring in 2 pediatric survivors
      with out-of-hospital cardiac arrest.
AB  - In pediatric out-of-hospital cardiac arrest (POHCA), cardiovascular monitoring
      tools have improved resuscitative endeavors and cardiovascular outcomes but with
      still poor neurologic outcomes. Regarding cardiac arrest in patients with
      congenital heart disease during surgery, the application of cerebral oximetry
      with blood volume index (BVI) during the resuscitation has shown significant
      results and prognostic significance. We present 2 POHCA patients who had cerebral
      oximetry with BVI monitoring during their arrest and postarrest phase in the
      emergency department and its potential prognostic aspect.Basic procedures include
      left and right cerebral oximetry with BVI monitoring at every 5-second interval
      during cardiac arrest, resuscitation, and postarrest in 2 POHCA patients in the
      pediatric emergency department.Regional cerebral tissue oxygen saturation (rSo2)
      with BVI readings in these 2 POHCA survivors demonstrated interesting cerebral
      physiology, blood flow, and potential prognostic outcome. In 1 patient, the
      reference range of cerebral rSo2 with positive blood flow during arrest and
      postarrest phases consistently occurred. This neurologic monitoring had its
      significance when the resuscitation effectiveness was used and end-tidal CO2
      changes were lost. The other patient's cerebral rSo2 with simultaneous BVI
      readings and trending showed the effectiveness of the emergency medical services
      (EMS) resuscitation.Cerebral oximetry with cerebral blood flow index monitoring
      in these POHCA survivors demonstrates compelling periarrest and postarrest
      cerebral physiology information and prognostication. Cerebral oximetry with
      cerebral BVI monitoring during these arrest phases has potential as a neurologic
      monitor for the resuscitative intervention's effectiveness and its possible
      neurologic prognostic application in the pediatric OCHA patients.

PMID- 24275044
TI  - Cecal pneumatosis intestinalis in obstructing sigmoid cancer: emergency metallic
      stenting.
AB  - An 85-year-old man presented with acute abdomen. Abdominal computed tomography
      revealed obstructing sigmoid colon cancer with pneumatosis intestinalis of the
      ascending colon. A surgeon was consulted for colonic obstruction with impending
      sepsis, who declined surgery considering the patient's advanced age. After
      discussion, the patient consented for emergent endoscopic metallic colonic stent
      placement. Complete obstruction of the lumen was observed at the sigmoid colon,
      followed by successful metallic colonic stent placement through the obstructed
      area. Normal stool passage was achieved after this, and the patient survived the
      9-month follow-up period. Acute colonic obstruction from obstructive colon cancer
      requires emergency management, wherein the presence of pneumatosis intestinalis
      poses a high risk of cecal perforation. Emergency endoscopic colonic metallic
      stent placement provides an alternative therapy, particularly when surgery is not
      feasible, as described here.

PMID- 24275045
TI  - Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the
      amygdala in the anxiolytic effect of chronic antidepressant treatment.
AB  - Facilitation of serotonin 2C- and 1A-receptor (5-HT2C-R and 5-HT1A-R) mediated
      neurotransmission in the basolateral nucleus of the amygdala (BLA) has been
      associated with anxiogenic and anxiolytic effects, respectively. It has been also
      shown that stimulation of BLA 5-HT2C-Rs underlies the anxiogenic effect caused by
      acute systemic administration of the antidepressants imipramine or fluoxetine.
      Here we investigated whether chronic treatment with these two antidepressants,
      which causes anxiolytic effects, decreases the responsiveness of these receptors
      in the BLA. We also investigated whether the blockage of 5-HT1A-Rs in the same
      amygdala nucleus alters the anxiolytic effect of chronic imipramine treatment.
      The results showed that in male Wistar rats intra-BLA injection of the 5-HT2C-R
      agonist MK-212 facilitated inhibitory avoidance acquisition in the elevated T
      maze and decreased the percentage of time spent by the animals in the lit
      compartment of the light-dark transition test, indicating an anxiogenic effect.
      Chronic (21 days) systemic treatment with imipramine (5 or 15 mg/kg) or
      fluoxetine (10 mg/kg) abolished these effects of MK-212. Acute administration of
      imipramine (5 mg/kg) failed to interfere with MK-212 effects in both tests. Intra
      BLA injection of the 5-HT1A antagonist WAY-100635 blocked the anxiolytic, but not
      the panicolytic, effect of imipramine in the tests used. Our findings indicate
      that both a reduction in 5-HT2C-R- and a facilitation of 5-HT1A-R-mediated
      neurotransmission in the BLA are involved in the anxiolytic effect of
      antidepressant drugs. 

PMID- 24275046
TI  - Monoamine transporter and receptor interaction profiles of a new series of
      designer cathinones.
AB  - Psychoactive beta-keto amphetamines (cathinones) are sold as "bath salts" or
      "legal highs" and recreationally abused. We characterized the pharmacology of a
      new series of cathinones, including methedrone, 4-methylethcathinone (4-MEC), 3
      fluoromethcathinone (3-FMC), pentylone, ethcathinone, buphedrone, pentedrone, and
      N,N-dimethylcathinone. We investigated norepinephrine (NE), dopamine (DA), and
      serotonin (5-HT) uptake inhibition using human embryonic kidney 293 (HEK 293)
      cells that express the respective human monoamine transporter, the drug-induced
      efflux of NE, DA, and 5-HT from monoamine-preloaded cells, and binding affinity
      to monoamine transporters and receptors. All of the cathinones were potent NE
      uptake inhibitors but differed in their DA vs. 5-HT transporter inhibition
      profiles and monoamine release effects. Methedrone was a more potent 5-HT than DA
      transporter inhibitor and released NE and 5-HT similar to para
      methoxymethamphetamine (PMMA), para-methoxyamphetamine (PMA), 4
      methylthioamphetamine (4-MTA), and 3,4-methylenedioxymethamphetamine (MDMA). 4
      MEC and pentylone equipotently inhibited all of the monoamine transporters and
      released 5-HT. Ethcathinone and 3-FMC inhibited NE and DA uptake and released NE,
      and 3-FMC also released DA similar to N-ethylamphetamine and methamphetamine.
      Pentedrone and N,N-dimethylcathinone were non-releasing NE and DA uptake
      inhibitors as previously shown for pyrovalerone cathinones. Buphedrone
      preferentially inhibited NE and DA uptake and also released NE. None of the
      cathinones bound to rodent trace amine-associated receptor 1, in contrast to the
      non-beta-keto-amphetamines. None of the cathinones exhibited relevant binding to
      other monoamine receptors. In summary, we found considerable differences in the
      monoamine transporter interaction profiles among different cathinones and
      compared with related amphetamines. 

PMID- 24275047
TI  - Distribution of orientation of smooth muscle bundles does not change along human
      great and small varicose veins.
AB  - Wall remodeling in varicose veins is associated with hypertrophy of
      subendothelial tissue, increase in inner diameter, wrinkling and invagination of
      the endothelial layer. Due to structural alterations of the wall, the smooth
      muscle cells (SMCs) change their original circular and longitudinal orientations.
      Our aim was to quantify the volume fraction of circularly, longitudinally and
      obliquely oriented SMCs within both the inner and outer half of the wall of 11
      great saphenous varicose veins and five small saphenous varicose veins. Using
      stereological methods applied on cross-sections of the vessels regularly gained
      each 5 cm along the vessel we determined the wall thickness (846 +/- 319 MUm,
      mean +/- standard deviation), the volume fraction of circular SMCs in the inner
      (0.19 +/- 0.13) and outer (0.06 +/- 0.06) layers, the volume fraction of
      longitudinal SMCs in the inner (0.06 +/- 0.05) and outer (0.05 +/- 0.04) layers,
      the volume fraction of oblique SMCs in the inner (0.15 +/- 0.08) and outer (0.09
      +/- 0.08) layers, and the total volume fraction of SMCs in the inner (0.4 +/-
      0.1) and outer (0.21 +/- 0.09) layers. The volume fraction of SMCs with circular
      and oblique but not with longitudinal orientation was greater in the inner layer
      compared to the outer layer. The SMC orientation distribution was uniform along
      the varicose saphenous veins. With increasing wall thickness, the volume fraction
      of longitudinal and oblique SMC bundles increased in both layers at the expansion
      of circular SMC bundles. The main differences in the orientation of the SMCs in
      the inner and outer wall layers should be taken into account when computational
      modeling of varicose saphenous veins is attempted.

PMID- 24275048
TI  - Pseudo dislodgement of a stent due to crumpling of a coronary artery: a hitherto
      unreported complication of the "accordion effect".
AB  - The "accordion effect" is a mechanical remodeling of the arterial wall produced
      by endoluminal introduction of stiff guidewires, leading to vessel wall
      shortening and development of multiple eccentric constrictions. This phenomenon
      is unresponsive to vasodilators and may lead to unnecessary stenting of the
      pseudo-lesions. It must be suspected with the development of multiple lesions and
      when a tortuous artery assumes a linear shape after advancing distally a stiff
      wire. In the situation of a complete occlusion of the artery the diagnosis may be
      challenging. Stenting in this scenario can be demanding because of the difficulty
      to appropriately size the length of the stent to the true lesion. We present a
      case of an unrecognized accordion phenomenon in an occluded coronary artery with
      a long dissection treated with two stents that after retrieving the wire were
      insufficient to cover the whole dissection. 

PMID- 24275049
TI  - Invasive filamentous fungus infection with secondary cerebral vasculitis in a
      patient with no obvious immune suppression.
AB  - Invasive mold infections represent an emerging and important diagnostic
      challenge, especially in immunocompetent patients when microscopy and cultures of
      the biological fluids remain negative. A central nervous system localization is
      not common and the clinical presentation is aspecific. 

PMID- 24275050
TI  - Derivation of a No-Significant-Risk-Level (NSRL) for diethanolamine (DEA).
AB  - Diethanolamine (DEA) has been listed on the State of California's Proposition 65
      List. This listing is based in part on tumors reported in a National Toxicology
      Program (NTP) 2-year dermal carcinogenicity study in mice which found clear
      evidence of carcinogenic activity in B6C3F1 mice based on increased incidences of
      liver neoplasms in both sexes, and increased incidences of renal tubule neoplasms
      in males. Although considerable controversy exists on the relevance of the NTP
      study to humans, industries are obligated to comply with the Proposition 65
      labeling requirement and drinking water discharge prohibition, unless they are
      able to demonstrate that DEA levels in their products are below a specific No
      Significant Risk Level (NSRL). The State of California has not published an NSRL
      for DEA. In this article, a NSRL of 5.6 MUg/day and a life-stage-adjusted
      NSRL(adj) of 1.4 MUg/day are derived from the NTP carcinogenicity study using a
      benchmark dose modeling method based on the incidence of hepatocellular
      carcinomas in female mice, in accordance with the guidelines of California EPA.

PMID- 24275051
TI  - Scaphoid overstuffing: the effects of the dimensions of scaphoid reconstruction
      on scapholunate alignment.
AB  - PURPOSE: Osteochondral replacement of the proximal scaphoid has been reported
      using a vascularized flap from the medial femoral trochlea. A concern with this
      technique is the loss of stability of the scapholunate relationship with
      resection of the scaphoid proximal pole. Overexpansion of the scaphoid dimensions
      (overstuffing) during scaphoid reconstruction with the osteochondral flap may
      play a role in maintaining scapholunate alignment. Our purpose was to determine
      if overstuffing the scaphoid can correct rotatory carpal instability in a
      cadaveric model studied radiographically. METHODS: The radiolunate angle and
      scapholunate interval were measured for 5 fresh cadaver wrists. We completely
      incised the scapholunate interosseous ligament and performed an osteotomy to
      excise the proximal third of the scaphoid to simulate a proximal pole deficiency
      nonunion and create a dorsal intercalated segmental instability deformity.
      Radiographic measurements were repeated. The proximal pole of the scaphoid was
      replaced with its original piece of bone; radiographic measurements were repeated
      without scapholunate ligament repair. The osteotomy site was overstuffed with a 4
      mm sawbone spacer without scapholunate ligament repair, and radiographs were
      obtained. RESULTS: Sectioning of scapholunate ligaments and proximal pole
      excision successfully created carpal instability demonstrated by abnormal
      radiolunate angles. Without ligament repair, proximal pole replacement did not
      restore normal radiolunate angles. Expansion of the scaphoid dimensions corrected
      radiolunate angles on lateral unloaded radiographs and improved scapholunate
      intervals on clenched fist radiographs. These findings were statistically
      significant compared with the unexpanded (replaced) scaphoid. CONCLUSIONS: These
      findings suggest that scaphoid reconstruction that results in expansion of the
      scaphoid's normal dimensions will restore carpal alignment without scapholunate
      ligament reconstruction. CLINICAL RELEVANCE: Osteochondral reconstruction of
      difficult proximal pole nonunions may not require any preservation or
      reconstruction of scapholunate integrity if the reconstruction expands the normal
      dimensions of the native scaphoid. Scapholunate interval and carpal alignment may
      be restored by scaphoid over stuffing. The effects on increased contact pressure
      and range of motion require further investigation.

PMID- 24275052
TI  - Long-term results following surgical treatment of elbow deformity in patients
      with cerebral palsy.
AB  - PURPOSE: To evaluate the long-term results of surgical intervention for elbow
      flexion deformity in cerebral palsy. We hypothesized that improvements in elbow
      extension and flexion posture angle at ambulation would be maintained over time
      with preservation of active flexion. METHODS: A total of 23 patients (23 elbows)
      were available for long-term follow-up. Patients had fixed elbow contractures
      less than 45 degrees  and were treated with partial elbow muscle lengthening.
      Active and passive range of motion and elbow flexion posture during ambulation
      were measured at each follow-up, and longitudinal results were compared. RESULTS:
      Active extension and flexion posture angle during ambulation improved 12 degrees 
      and 63 degrees , respectively, with an 8 degrees  loss of active flexion.
      CONCLUSIONS: Soft tissue lengthening of the anterior elbow can provide
      statistically significant lasting improvements in active extension and flexion
      posture during ambulation in patients with cerebral palsy. Our long-term findings
      substantiate previously reported short-term results. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 24275053
TI  - ASSH Presidential Address: power of inclusion.

PMID- 24275054
TI  - Arthroscopic ligamentoplasty of the dorsal and volar portions of the scapholunate
      ligament.
AB  - Classical arthroscopic techniques for scapholunate instability consist of
      debridement, thermal shrinkage, and percutaneous pinning. Good results are
      obtained in acute lesions or in chronic partial tears, but they are less
      predictable when the lesion is complete, because of the poor healing capacity of
      the scapholunate ligament and because it is not possible to perform an anatomic
      ligamentous reconstruction with these techniques. Open techniques are thus
      required for reconstruction, but they damage the soft tissues. We recently
      published a description and cadaver study of an arthroscopic ligamentoplasty,
      trying to combine the advantages of arthroscopic techniques (minimally invasive
      surgery) and open techniques (reconstruction of the ligament). With this
      approach, it is possible to reconstruct the dorsal scapholunate ligament and the
      secondary stabilizers while causing minimal damage to the soft tissues and
      avoiding injury to the posterior interosseous nerve and detachment of the dorsal
      intercarpal ligament. The current report describes an additional step to this
      technique with which it is possible to reconstruct the volar portion of the
      scapholunate ligament. We also describe an early mobilization postoperative
      protocol that we believe is equally important. 

PMID- 24275055
TI  - Fibrin glue augmentation for flexor tendon repair increases friction compared
      with epitendinous suture.
AB  - PURPOSE: To compare the gliding resistance, repair gapping, and ultimate strength
      of a common suture construct with a modified construct with fibrin glue
      augmentation. METHODS: Twelve human cadaveric flexor digitorum profundus tendons
      were transected and repaired with a 4-strand core suture. Specimens were divided
      into 2 groups and augmented with epitendinous suture (n = 6) or fibrin glue (n =
      6). We compared gliding resistance, 2-mm gapping, and ultimate strength of the
      repaired tendon between groups. RESULTS: The linear stiffness, force to produce a
      2-mm gap, and ultimate failure were similar in both repair methods. However, the
      4-strand suture repair with fibrin glue augmentation displayed significantly
      higher gliding resistance compared with the 4-strand suture with a running
      epitendinous suture. CONCLUSIONS: The significantly increased gliding resistance
      associated with fibrin glue raises questions regarding the use of this material
      for flexor tendon repair augmentation. CLINICAL RELEVANCE: In a human cadaveric
      study, fibrin glue augmentation to zone II flexor tendon repairs significantly
      increased friction in the tendon sheath compared with an epitendinous suture.

PMID- 24275056
TI  - A tricky diagnosis.

PMID- 24275057
TI  - In reply.

PMID- 24275058
TI  - Preventing air leakage in negative atmospheric pressure therapy for open
      fractures treated with external fixators.

PMID- 24275059
TI  - Nanosecond laser switching of surface wettability and epitaxial integration of c
      axis ZnO thin films with Si(111) substrates.
AB  - We have achieved integration of polar ZnO[0001] epitaxial thin films with Si(111)
      substrates where cubic yttria-stabilized zirconia (c-YSZ) was used as a template
      on a Si(111) substrate. Using XRD (theta-2theta and phi scans) and HRTEM
      techniques, the epitaxial relationship between the ZnO and the c-YSZ layers was
      shown to be [0001]ZnO || [111]YSZ and [21-1-0]ZnO || [1-01](c-YSZ), where the [21
      1-0] direction lies in the (0001) plane, and the [1-01] direction lies in the
      (111) plane. Similar studies on the c-YSZ/Si interface revealed epitaxy as
      (111)YSZ || (111)Si and in-plane (110)YSZ || (110)Si. HRTEM micrographs revealed
      atomically sharp and crystallographically continuous interfaces. The ZnO
      epilayers were subsequently laser annealed by a single pulse of a nanosecond
      excimer KrF laser. It was shown that the hydrophobic behavior of the pristine
      sample became hydrophilic after laser treatment. XPS was employed to study the
      effect of laser treatment on surface stoichiometry of the ZnO epilayers. The
      results revealed the formation of oxygen vacancies, which are envisaged to
      control the observed hydrophilic behavior. Our AFM studies showed surface
      smoothing due to the coupling of the high energy laser beam with the surface. The
      importance of integration of c-axis ZnO with Si(111) substrates is emphasized
      using the paradigm of domain matching epitaxy on the c-YSZ[111] buffer platform
      along with their out-of-plane orientation, which leads to improvement of the
      performance of the solid-state devices. The observed ultrafast response and
      switching in photochemical characteristics provide new opportunities for
      application of ZnO in smart catalysts, sensors, membranes, DNA self-assembly and
      multifunctional devices.

PMID- 24275062
TI  - UV light and urban pollution: bad cocktail for mosquitoes?
AB  - Mosquito breeding sites consist of water pools, which can either be large open
      areas or highly covered ponds with vegetation, thus with different light
      exposures combined with the presence in water of xenobiotics including polycyclic
      aromatic hydrocarbons (PAHs) generated by urban pollution. UV light and PAHs are
      abiotic factors known to both affect the mosquito insecticide resistance status.
      Nonetheless, their potential combined effects on the mosquito physiology have
      never been investigated. The present article aims at describing the effects of UV
      exposure alongside water contamination with two major PAH pollutants
      (fluoranthene and benzo[a]pyrene) on a laboratory population of the yellow fever
      mosquito Aedes aegypti. To evaluate the effects of PAH exposure and low energetic
      UV (UV-A) irradiation on mosquitoes, different parameters were measured
      including: (1) The PAH localization and its impact on cell mortality by
      fluorescent microscopy; (2) The detoxification capacities (cytochrome P450,
      glutathione-S-transferase, esterase); (3) The responses to oxidative stress
      (Reactive Oxygen Species-ROS) and (4) The tolerance of mosquito larvae to a
      bioinsecticide (Bacillus thuringiensis subsp. israelensis-Bti) and to five
      chemical insecticides (DDT, imidacloprid, permethrin, propoxur and temephos).
      Contrasting effects regarding mosquito cell mortality, detoxification and
      oxidative stress were observed as being dependent on the pollutant considered,
      despite the fact that the two PAHs belong to the same family. Moreover, UV is
      able to modify pollutant effects on mosquitoes, including tolerance to three
      insecticides (imidacloprid, propoxur and temephos), cell damage and response to
      oxidative stress. Taken together, our results suggest that UV and pollution,
      individually or in combination, are abiotic parameters that can affect the
      physiology and insecticide tolerance of mosquitoes; but the complexity of their
      direct effect and of their interaction will require further investigation to know
      in which condition they can affect the efficacy of insecticide-based vector
      control strategies in the field. 

PMID- 24275061
TI  - IFNgamma-stimulated dendritic cell exosomes as a potential therapeutic for
      remyelination.
AB  - Dendritic cells (DCs) release exosomes with different characteristics based on
      stimulus. Here, we showed that DC cultures stimulated with low-level IFNgamma
      released exosomes (IFNgamma-DC-Exos) that contained microRNA species that can
      increase baseline myelination, reduce oxidative stress, and improve remyelination
      following acute lysolecithin-induced demyelination. Furthermore, nasally
      administered IFNgamma-DC-Exos increased CNS myelination in vivo. IFNgamma-DC-Exos
      were preferentially taken up by oligodendrocytes, suggesting that they directly
      impact oligodendrocytes to increase myelination. Thus, our results show great
      potential for use of these IFNgamma-DC-Exos as a therapeutic to promote
      remyelination in multiple sclerosis and dysmyelinating syndromes. 

PMID- 24275064
TI  - Dexterity training improves manual precision in patients affected by essential
      tremor.
AB  - OBJECTIVE: To evaluate the effect of a short-term dexterity-training program on
      muscle tremor and the performance of hand precision tasks in patients with
      essential tremor (ET). DESIGN: Three testing sessions: baseline, after 4 weeks
      without any interventions (control), and after 4 weeks of dexterity-training
      carried out 3 times per week. SETTING: Biomechanics research laboratory.
      PARTICIPANTS: Patients (N=8) with a diagnosis of ET. INTERVENTION: Training
      program consisted of 12 dexterity training sessions where each session comprised
      4 tasks involving both goal-directed manual movements and hand postural
      exercises. MAIN OUTCOME MEASURES: Testing included an ET-specific quality of life
      questionnaire and postural and kinetic tremor assessments. Each training session
      was scored to evaluate the performance. RESULTS: After training, improvements
      were observed in the performance of the 2 goal-directed tasks (P<.01); however,
      postural and kinetic tremor did not change. CONCLUSIONS: This study suggests that
      dexterity training could be effective in increasing fine manual control during
      goal-directed movements, which are known to be the most compromised in this
      pathology. The absence of a decrease in tremor severity highlights the necessity
      for developing this novel training technique further, perhaps over a longer
      period of time. This study could provide guidelines for the prescription of self
      directed and personalized home-based exercises and will offer clinicians a
      treatment that might be used as an adjuvant or an alternative to the classical
      pharmacotherapy.

PMID- 24275063
TI  - Clinical and neuropsychological long-term outcomes after late recovery of
      responsiveness: a case series.
AB  - OBJECTIVE: To report clinical conditions and neuropsychological functioning of
      patients with late recovery of responsiveness at least 5 years after injury.
      DESIGN: Patient series. SETTING: Patients discharged from an inpatient
      rehabilitation unit. PARTICIPANTS: Patients (N=13) who recovered from a
      vegetative state 1 year after severe traumatic brain injury or 6 months after
      nontraumatic brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Coma Recovery Scale-Revised, Disability Rating Scale, and FIM. For patients who
      recovered full consciousness, neuropsychological tests specifically adapted for
      patients with very severe disabilities were used. RESULTS: After regaining
      responsiveness, 2 patients died because of severe clinical complications. Among
      the remaining 11 patients, 5 were still in a minimally conscious state at their
      last assessment, but 4 of them had recovered some complex behavioral responses to
      the environment (eg, they could follow simple commands, albeit inconsistently).
      Six patients had emerged from a minimally conscious state at the last evaluation.
      Severe functional disability was present in both patients who were conscious and
      patients who were minimally conscious. No patient was autonomous in common daily
      life activities or in transfers. All patients who were conscious showed variable
      cognitive impairments, and some of them also developed behavioral and
      psychological symptoms. However, such disturbances did not impede the patients'
      interaction with relatives and caregivers. CONCLUSIONS: This study provides
      systematic data about the course of the disease in a cohort of patients that was
      previously considered as exceptional. Patients with late recovery show a variable
      degree of functional recovery, although they experience marked residual motor and
      cognitive disabilities. The present findings contribute to enhance the
      understanding of the course of the disease in patients with late recovery and
      might help clinicians optimize the levels of care and provide the patients'
      families with correct information.

PMID- 24275060
TI  - Role of childhood infection in the sequelae of H. pylori disease.
AB  - The persistence of Helicobacter pylori infection plays a fundamental role in the
      development of H. pylori-associated complications. Since the majority of infected
      persons acquire the bacteria during early childhood, an examination of the
      immunobiology of H. pylori infection in children compared with that of adults may
      help identify host factors that contribute to persistent infection. Therefore, we
      begin our review of the role of persistence in H. pylori disease with an
      assessment of the clinical features of H. pylori infection in children. We next
      review the bacterial factors that promote colonization and evasion of host
      defense mechanisms. We then focus our attention on the early host immunological
      factors that promote persistence of the infection and its complications in humans
      and mouse models. We also highlight topics in which further research is needed.
      An examination of how immunological factors cause divergent manifestations of H.
      pylori infection in children compared with adults may provide new insight for
      therapeutic modification or prevention of persistent H. pylori infection and its
      complications. 

PMID- 24275065
TI  - Survival in persons with traumatic spinal cord injury receiving structured follow
      up in South India.
AB  - OBJECTIVE: To assess the survival in persons with traumatic spinal cord injury
      (SCI) receiving structured follow-up in South India. DESIGN: Retrospective study.
      SETTING: Rehabilitation center. PARTICIPANTS: Persons with traumatic SCI (N=490)
      residing within a 100-km radius of the institute who were managed and regularly
      followed up by the rehabilitation center between the years 1981 and 2011.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survival rates and
      mortality risk factors. Measures were estimated using the product limit (Kaplan
      Meier) method and the Cox model. RESULTS: The survival rate after SCI was 86%
      after 5 years, 71% after 15 years, and 58% after 25 years. Survival of persons
      with complete high cervical injury is substantially low compared with other
      levels of SCI. Level of injury and extent of lesion (Frankel classification
      and/or American Spinal Injury Association Impairment Scale) play a significant
      role in predicting survival of this population. CONCLUSIONS: Survival rates of
      regularly followed-up persons with SCI from this study show promising results,
      though survival rates are lesser when compared with studies from developed
      countries. Better understanding of the predictors, causes of deaths,
      comprehensive rehabilitation, community integration, and regular follow-up could
      possibly assist in improving survival rates.

PMID- 24275066
TI  - Applying the Quadruple Process model to evaluate change in implicit attitudinal
      responses during therapy for panic disorder.
AB  - OBJECTIVE: This study explored the automatic and controlled processes that may
      influence performance on an implicit measure across cognitive-behavioral group
      therapy for panic disorder. METHOD: The Quadruple Process model was applied to
      error scores from an Implicit Association Test evaluating associations between
      the concepts Me (vs. Not Me) + Calm (vs. Panicked) to evaluate four distinct
      processes: Association Activation, Detection, Guessing, and Overcoming Bias.
      Parameter estimates were calculated in the panic group (n = 28) across each
      treatment session where the IAT was administered, and at matched times when the
      IAT was completed in the healthy control group (n = 31). RESULTS: Association
      Activation for Me + Calm became stronger over treatment for participants in the
      panic group, demonstrating that it is possible to change automatically activated
      associations in memory (vs. simply overriding those associations) in a clinical
      sample via therapy. As well, the Guessing bias toward the calm category increased
      over treatment for participants in the panic group. CONCLUSIONS: This research
      evaluates key tenets about the role of automatic processing in cognitive models
      of anxiety, and emphasizes the viability of changing the actual activation of
      automatic associations in the context of treatment, versus only changing a
      person's ability to use reflective processing to overcome biased automatic
      processing.

PMID- 24275067
TI  - Therapist effects and the outcome-alliance correlation in cognitive behavioral
      therapy for panic disorder with agoraphobia.
AB  - Although the alliance-outcome correlation is well established, no published
      studies to date have separated between therapists' and patients' contributions
      while controlling for early symptom change. In this study, we examined therapist
      effects in two trials of CBT for panic disorder with agoraphobia (PDA) and the
      impact of therapists' and patients' contribution to the alliance on outcome and
      attrition in one trial. Alliance ratings were obtained from patients and
      therapists early and late in treatment (n = 133). Data were analyzed using multi
      level modeling controlling for early symptom change. No therapist effects were
      found. The patients' contribution to the alliance predicted outcome (in both
      panic severity and anxiety sensitivity) and attrition. The therapists'
      contribution to the alliance predicted attrition but not outcome. Results suggest
      that the patient's contribution to the alliance plays an important role in CBT
      for PDA and that including common factors into research on CBT may help elucidate
      treatment processes. 

PMID- 24275068
TI  - Speech and language outcomes of very preterm infants.
AB  - Speech and language impairments of both simple and complex language functions are
      common among former preterm infants. Risk factors include lower gestational age
      and increasing illness severity including severe brain injury. Even in the
      absence of brain injury, however, altered brain maturation and vulnerability
      imposed by premature entrance to the extrauterine environment is associated with
      brain structural and microstructural changes. These alterations are associated
      with language impairments with lasting effects in childhood and adolescence and
      increased needs for speech therapy and education supports. Studies are needed to
      investigate language interventions which begin in the neonatal intensive care
      unit. 

PMID- 24275069
TI  - Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency
      in reducing PARP-1 activity, leading to inhibition of DNA repair.
AB  - Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of
      ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose)
      polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a
      sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein
      function as a critical structure in DNA recognition and binding. Since cellular
      poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status
      in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is
      equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition
      of DNA repair. To test this hypothesis, we compared the effects of arsenite
      exposure with zinc deficiency, created by using the membrane-permeable zinc
      chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in
      HaCat cells. Our results show that arsenite exposure and zinc deficiency had
      similar effects on PARP-1 protein, whereas supplemental zinc reversed these
      effects. To investigate the molecular mechanism of zinc loss induced by arsenite,
      ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy
      were utilized to examine arsenite binding and occupation of a peptide
      representing the first zinc finger of PARP-1. We found that arsenite binding as
      well as zinc loss altered the conformation of zinc finger structure which
      functionally leads to PARP-1 inhibition. These findings suggest that arsenite
      binding to PARP-1 protein created similar adverse biological effects as zinc
      deficiency, which establishes the molecular mechanism for zinc supplementation as
      a potentially effective treatment to reverse the detrimental outcomes of arsenic
      exposure. 

PMID- 24275070
TI  - Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic
      fatty liver disease in female adult offspring rats.
AB  - Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus
      and adult offspring. However, whether PEE increases the susceptibility to non
      alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism
      remain unknown. This study aimed to demonstrate an increased susceptibility to
      high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in
      female rat offspring with PEE. Rat model of intrauterine growth retardation
      (IUGR) was established by PEE, the female fetus and adult offspring that fed
      normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND
      group, serum corticosterone (CORT) slightly decreased and insulin-like growth
      factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD
      group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG)
      increased, with notable catch-up growth, higher metabolic status and NAFLD
      formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and
      lipid synthesis as well as reduced expression of lipid output were accompanied in
      PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low
      body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1
      expression as well as lipid output was down-regulated, while lipid synthesis
      significantly increased. Based on these findings, we propose a "two-programming"
      hypothesis for an increased susceptibility to HFD-induced NAFLD in female
      offspring of PEE. That is, the intrauterine programming of liver glucose and
      lipid metabolic function is "the first programming", and postnatal adaptive catch
      up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the
      second programming". 

PMID- 24275071
TI  - Genotype-phenotype analysis in inherited prion disease with eight octapeptide
      repeat insertional mutation.
AB  - A minority of inherited prion diseases (IPD) are caused by four to 12 extra
      octapeptide repeat insertions (OPRI) in the prion protein gene (PRNP). Only four
      families affected by IPD with 8-OPRI have been reported, one of them was a three
      generation Swedish kindred in which four of seven affected subjects had chorea
      which was initially attributed to Huntington's disease (HD). Following the
      exclusion of HD, this phenotype was labeled Huntington disease-like 1 (HDL1).
      Here, we provide an update on the Swedish 8-OPRI family, describe the clinical
      features of one of its affected members with video-recordings, compare the four 8
      OPRI families and study the effect of PRNP polymorphic codon 129 and gender on
      phenotype. Surprisingly, the Swedish kindred displayed the longest survival of
      all of the 8-OPRI families with a mean of 15.1 years from onset of symptoms.
      Subjects with PRNP polymorphic codon 129M in the mutated allele had significantly
      earlier age of onset, longer survival and earlier age of death than 129V
      subjects. Homozygous 129MM had earlier age of onset than 129VV. Females had a
      significantly earlier age of onset and earlier age of death than males. Up to 50%
      of variability in age of onset was conferred by the combined effect of PRNP
      polymorphic codon 129 and gender. An inverse correlation between early age of
      onset and long survival was found for this mutation. 

PMID- 24275072
TI  - Benchmarking the use of a rapid response team by surgical services at a tertiary
      care hospital.
AB  - BACKGROUND: Rapid response teams (RRT) are used to prevent adverse events in
      patients with acute clinical deterioration, and to save costs of unnecessary
      transfer in patients with lower-acuity problems. However, determining the optimal
      use of RRT services is challenging. One method of benchmarking performance is to
      determine whether a department's event rate is commensurate with its volume and
      acuity. STUDY DESIGN: Using admissions between 2009 and 2011 to 18 distinct
      surgical services at a tertiary care center, we developed logistic regression
      models to predict RRT activation, accounting for days at-risk for RRT and patient
      acuity, using claims modifiers for risk of mortality (ROM) and severity of
      illness (SOI). The model was used to compute observed-to-expected (O/E) RRT use
      by service. RESULTS: Of 45,651 admissions, 728 (1.6%, or 3.2 per 1,000 inpatient
      days) resulted in 1 or more RRT activations. Use varied widely across services
      (0.4% to 6.2% of admissions; 1.39 to 8.73 per 1,000 inpatient days, unadjusted).
      In the multivariable model, the greatest contributors to the likelihood of RRT
      were days at risk, SOI, and ROM. The O/E RRT use ranged from 0.32 to 2.82 across
      services, with 8 services having an observed value that was significantly higher
      or lower than predicted by the model. CONCLUSIONS: We developed a tool for
      identifying outlying use of an important institutional medical resource. The O/E
      computation provides a starting point for further investigation into the reasons
      for variability among services, and a benchmark for quality and process
      improvement efforts in patient safety.

PMID- 24275074
TI  - Minimally-invasive vs open pancreaticoduodenectomy: systematic review and meta
      analysis.

PMID- 24275073
TI  - Florida Initiative for Quality Cancer Care: improvements on colorectal cancer
      quality of care indicators during a 3-year interval.
AB  - BACKGROUND: The quality of cancer care has become a national priority; however,
      there are few ongoing efforts to assist medical oncology practices in identifying
      areas for improvement. The Florida Initiative for Quality Cancer Care is a
      consortium of 11 medical oncology practices that evaluates the quality of cancer
      care across Florida. Within this practice-based system of self-assessment, we
      determined adherence to colorectal cancer quality of care indicators (QCIs) in
      2006, disseminated results to each practice and reassessed adherence in 2009. The
      current report focuses on evaluating the direction and magnitude of change in
      adherence to QCIs for colorectal cancer patients between the 2 assessments. STUDY
      DESIGN: Medical records were reviewed for all colorectal cancer patients seen by
      a medical oncologist in 2006 (n = 489) and 2009 (n = 511) at 10 participating
      practices. Thirty-five indicators were evaluated individually and changes in QCI
      adherence over time and by site were examined. RESULTS: Significant improvements
      were noted from 2006 to 2009, with large gains in surgical/pathological QCIs (eg,
      documenting rectal radial margin status, lymphovascular invasion, and the review
      of >= 12 lymph nodes) and medical oncology QCIs (documenting planned treatment
      regimen and providing recommended neoadjuvant regimens). Documentation of
      perineural invasion and radial margins significantly improved; however, adherence
      remained low (47% and 71%, respectively). There was significant variability in
      adherence for some QCIs across institutions at follow-up. CONCLUSIONS: The
      Florida Initiative for Quality Cancer Care practices conducted self-directed
      quality-improvement efforts during a 3-year interval and overall adherence to
      QCIs improved. However, adherence remained low for several indicators, suggesting
      that organized improvement efforts might be needed for QCIs that remained
      consistently low over time. Findings demonstrate how efforts such as the Florida
      Initiative for Quality Cancer Care are useful for evaluating and improving the
      quality of cancer care at a regional level.

PMID- 24275075
TI  - Distinct effects of duration of untreated psychosis on brain cortical activities
      in different treatment phases of schizophrenia: a multi-channel near-infrared
      spectroscopy study.
AB  - BACKGROUND: Duration of untreated psychosis (DUP) has been shown to be associated
      with both poor short-term and long-term outcomes in schizophrenia. Even so, few
      studies have used functional neuroimaging to investigate DUP in schizophrenia. In
      the present study, we used near-infrared spectroscopy (NIRS) to investigate the
      influence of DUP on brain functions during a verbal fluency test (VFT) in
      patients with schizophrenia. METHODS: A total of 62 patients with schizophrenia
      were included. They were categorized into either short treatment (<=6months,
      n=33) or long treatment (>6months, n=29) groups based on their duration of
      treatment. Hemodynamic changes over the frontotemporal regions during a VFT were
      measured using multi-channel NIRS. We examined the associations between DUP and
      hemodynamic changes in each group to explore if there were different effects of
      DUP on brain cortical activity at different treatment durations. RESULTS: In the
      long treatment group, we found significant associations between a longer DUP and
      decreased cortical activity approximately at the left inferior frontal gyrus,
      left middle frontal gyrus, left postcentral gyrus, right precentral gyrus,
      bilateral superior temporal gyrus, and bilateral middle temporal gyrus, whereas
      no associations between DUP and brain cortical activity were observed in the
      short treatment group. CONCLUSIONS: Our results indicated that longer DUP may be
      associated with decreased level of cortical activities over the frontotemporal
      regions in the long-term. Early detection and intervention of psychosis that
      shortens DUP might help to improve the long-term outcomes in patients with
      schizophrenia.

PMID- 24275077
TI  - Optomechanical interactions in two-dimensional Si and GaAs phoXonic cavities.
AB  - We investigate theoretically the optomechanical interactions inside cavities
      created in two-dimensional infinite phoXonic crystals constituted by a square
      array of holes in silicon (Si) and gallium arsenide (GaAs) matrices. The cavity
      is simply obtained by removing one hole in the perfect crystal. Our calculations
      take into account two mechanisms that contribute to the optomechanical coupling,
      namely the bulk photoelastic effect and the deformations of the interfaces due to
      the acoustic strain. The coupling strength is estimated by two different methods,
      modulation of the photonic mode frequency during one period of the acoustic
      oscillations and calculation of the optomechanical coupling rate. We discuss the
      important roles of the symmetry and degeneracy of the modes to discriminate which
      ones are not able to interact efficiently. Calculations in Si and GaAs crystals
      at different optical wavelengths emphasize the dependence of the photoelastic
      contribution to the optomechanical interaction as a function of material and
      wavelength, especially owing to the significant variation of the photoelastic
      coefficients near the semiconductor band gap. 

PMID- 24275076
TI  - Acute, but not repeated, administration of the neurotensin NTS1 receptor agonist
      PD149163 decreases conditioned footshock-induced ultrasonic vocalizations in
      rats.
AB  - Neurotensin is an endogenous neuropeptide that has significant interactions with
      monoamine neurotransmitter systems. To date, neurotensin NTS1 receptor agonists,
      such as PD149163, have been primarily evaluated for the treatment for
      schizophrenia, drug addiction, and pain. Recently, PD149163 was found to
      attenuate fear-potentiated startle in rats, an experimental procedure used for
      screening anxiolytic drugs. The present study sought to assess these findings
      through testing PD149163 in a conditioned footshock-induced ultrasonic
      vocalization (USV) model. Conditioning was conducted in male Wistar rats using
      chambers equipped with shock grid floors and an ultrasonic vocalization detector.
      PD149163 and the 5-HT1A receptor partial agonist buspirone produced a
      statistically significant reduction of 22kHz USV counts. The typical
      antipsychotic haloperidol also reduced 22kHz USV counts, but did so at cataleptic
      doses. Ten days of repeated administration of PD149163 abolished the inhibitory
      effects of PD149163 on 22kHz USVs. These findings further support an anxiolytic
      profile for PD149163. However, tolerance to these effects may limit the utility
      of these drugs for the treatment of anxiety. 

PMID- 24275078
TI  - The present and future of microplastic pollution in the marine environment.
AB  - Recently, research examining the occurrence of microplastics in the marine
      environment has substantially increased. Field and laboratory work regularly
      provide new evidence on the fate of microplastic debris. This debris has been
      observed within every marine habitat. In this study, at least 101 peer-reviewed
      papers investigating microplastic pollution were critically analysed
      (Supplementary material). Microplastics are commonly studied in relation to (1)
      plankton samples, (2) sandy and muddy sediments, (3) vertebrate and invertebrate
      ingestion, and (4) chemical pollutant interactions. All of the marine organism
      groups are at an eminent risk of interacting with microplastics according to the
      available literature. Dozens of works on other relevant issues (i.e., polymer
      decay at sea, new sampling and laboratory methods, emerging sources,
      externalities) were also analysed and discussed. This paper provides the first in
      depth exploration of the effects of microplastics on the marine environment and
      biota. The number of scientific publications will increase in response to present
      and projected plastic uses and discard patterns. Therefore, new themes and
      important approaches for future work are proposed. 

PMID- 24275079
TI  - Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal
      circulation.
AB  - OBJECTIVE: Extracorporeal circulation (ECC) is regularly applied to maintain
      organ perfusion during major aortic and cardiovascular surgery. During
      thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion
      (SVP) results in changed microcirculatory perfusion (shift from the muscularis
      toward the mucosal small intestinal layer) in conjunction with macrohemodynamic
      hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim
      of this study was to assess in a porcine model whether ECC itself or the
      hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the
      small intestinal wall. METHODS: A thoracoabdominal aortic approach was performed
      in 15 healthy pigs divided equally into three groups: group I, control; group II,
      thoracic aortic cross-clamping with distal aortic perfusion; and group III,
      thoracic aortic cross-clamping with distal aortic perfusion and SVP.
      Macrocirculatory and microcirculatory blood flow was assessed by transit time
      ultrasound volume flow measurement and fluorescent microspheres. In addition,
      markers for metabolism and intestinal ischemia-reperfusion injury were
      determined. RESULTS: ECC with a roller pump induced a significant switch from the
      muscularis and mucosal layer of the small intestine, even with adequate
      macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005;
      group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased
      significantly in groups II (>30%) and III (>40%) in the beginning of the ECC
      compared with the control (group I vs II, P = .0037; group I vs III, P = .0062).
      Lactate concentrations and pH values did not differ between groups I and II; but
      group III demonstrated a significant shifting toward a lactate-associated
      acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001).
      CONCLUSIONS: We demonstrated a significant shifting between the small intestinal
      gut wall layers induced by roller pump-driven ECC. The shift occurs independently
      of macrohemodynamics, with a significant effect on aerobic metabolism in the gut
      wall. Consequently, an optimal intestinal perfusion cannot be guaranteed by a
      roller pump; therefore, perfusion techniques need to be optimized.

PMID- 24275080
TI  - Are cases of mumps in vaccinated patients attributable to mismatches in both
      vaccine T-cell and B-cell epitopes?: An immunoinformatic analysis.
AB  - Resurgent mumps outbreaks have raised questions about the current efficacy of
      mumps vaccines. We have applied immunoinformatics techniques based on principal
      component analysis to evaluate patterns in predicted B-cell linear epitopes, MHC
      binding affinity and cathepsin cleavage in the hemagglutinin neuraminidase
      protein of vaccine strains and wild-type mumps isolates. We have mapped predicted
      MHC-peptide binding for 37 MHC-I and 28 MHC-II alleles and predicted cleavage by
      cathepsin B, L and S. By all measures we applied Jeryl-Lynn JL5 major strain is
      an outlier with immunomic features arising from a small number of amino acid
      changes that distinguish it from other virus strains. Individuals vaccinated with
      Jeryl-Lynn who are not exposed to wild-type virus until their protective antibody
      titer has waned may be unable to recall a protective immune response when exposed
      to wild-type virus. Dependence on serology to evaluate mumps vaccines may have
      overemphasized the conservation of one neutralizing antibody epitope, at the
      expense of monitoring other related changes in the HN protein that could affect
      recall responses. 

PMID- 24275081
TI  - GdpS contributes to Staphylococcus aureus biofilm formation by regulation of eDNA
      release.
AB  - In Staphylococcus aureus, the role of the GGDEF domain-containing protein GdpS
      remains poorly understood. Previous studies reported that gdpS mutant strains had
      decreased biofilm formation due to changes in icaADBC expression that were
      independent of cyclic-di-GMP levels. We deleted gdpS in three unrelated S. aureus
      isolates, and analyzed the resultant mutants for alterations in biofilm
      formation, metabolism and transcription. Dynamic imaging during biofilm
      development showed that GdpS inhibited early biofilm formation in only two out of
      the three strains examined, without affecting bacterial survival. However,
      quantification of biofilm formation using crystal violet staining revealed that
      inactivation of gdpS affected biofilm formation in all three studied strains.
      Extraction of metabolites from S. aureus cells confirmed the absence of cyclic-di
      GMP, suggesting that biofilm formation in this species differs from that in other
      Gram-positive organisms. In addition, targeted mutagenesis demonstrated that the
      GGDEF domain was not required for GdpS activity. Transcriptomic analysis revealed
      that the vast majority of GGDEF-regulated genes were involved in virulence,
      metabolism, cell wall biogenesis and eDNA release. Finally, expression of lrgAB
      or deletion of cidABC in a strain lacking gdpS confirmed the role of GdpS on
      regulation of eDNA production that occurred without an increase in cell
      autolysis, but with a late increase in holin-mediated autolysis, in the presence
      of high oxacillin concentrations. In summary, S. aureus GdpS contributes to cell
      to-cell interactions during early biofilm formation by influencing expression of
      lrgAB and cidABC mediated eDNA release. We conclude that GdpS acts as a negative
      regulator of eDNA release. 

PMID- 24275082
TI  - Potential role of biofilms in deep cervical abscess.
AB  - OBJECTIVES: Deep neck abscesses are complex head & neck problems that can lead to
      significant complications including life threatening infections. It is understood
      that the pathology of these infections is primarily polymicrobial. Although broad
      spectrum antibiotics can be effective for small abscesses, larger abscesses can
      be recalcitrant and difficult to treat with antibiotics. It has been demonstrated
      for several infectious diseases, including some of head & neck, that biofilm
      phenotypes present a unique model for recurrence and chronicity of infectious
      diseases. It is suspected that biofilm phenotypes could play a crucial role in
      the recalcitrance of large deep neck abscesses. This study presents initial
      evidence indicating the presence of polymicrobial biofilms in deep neck space
      infections. METHODS: Fourteen samples obtained via biopsy of abscess walls from
      deep neck spaces of patients undergoing surgical drainage. Eight patients were
      male and 6 were female. All but one patient were pediatric with ages ranging from
      18 months to 32 years. All samples were processed and analyzed with scanning
      electron microscopy. RESULTS: Electron micrographs of 12 out of 14 specimens
      showed discrete biofilm architecture with individual bacteria, both rods and
      cocci, embedded within the matrix. This was starkly different from tissue
      surfaces devoid of biofilms. CONCLUSIONS: This initial evidence suggests that
      biofilm phenotypes could play a role in the pathogenesis and recalcitrance of
      deep neck infections, particularly in larger abscesses.

PMID- 24275083
TI  - Conversion of yeast mannan polysaccharide in mannose oligosaccharides with a
      thiopropargyl linker at the pseudo-reducing end.
AB  - Polysaccharides are useful sources of preformed glycosyl linkages and therefore
      convenient building blocks can be prepared from them upon application of a proper
      degradation and derivatization scheme. Following this idea, the alpha-(1->6)
      linkages of this polysaccharide were broken applying acetolysis reaction and the
      pseudo-reducing position of the resulting acetylated mannose oligosaccharides was
      functionalized with a thiopropargyl appendage through thiourea activation of the
      related glycosyl iodides. Deacetylation of the final products and optimization of
      the purification procedures are discussed. The best yields were observed
      combining size exclusion chromatography and HPLC. Nine different
      oligosaccharides, from mono- to tetrasaccharides, mainly alpha-configured at the
      pseudo-reducing terminal, were obtained in pure form, presenting the propargyl
      appendage, a feature that makes them suitable substrates for successive
      functionalizations. 

PMID- 24275084
TI  - Cyanotoxin occurrence and potentially toxin producing cyanobacteria in
      freshwaters of Greece: a multi-disciplinary approach.
AB  - Cyanobacteria harmful algal blooms (or CyanoHABs) represent one of the most
      conspicuous waterborne microbial hazards in aquatic environments mostly due to
      the production of harmful secondary metabolites, known as cyanotoxins. In
      freshwaters of Greece only the presence of microcystins (MCs) has been reported
      despite the increasing occurrence of species able to produce other cyanotoxins
      too. In this paper, we studied the occurrence of potentially toxic cyanobacteria
      in water samples collected from six lakes and reservoirs in Greece. A multi
      technique approach was applied by the use of microscopy, molecular, and
      immunological methods. Cyanobacteria were found in all the sites ranging from 4.7
      * 103 to 5.3 * 108 individuals L-1, representing >70% of the total phytoplankton
      abundance. Microcystins (MCs), cylindrospermopsins (CYNs), and saxitoxins (STXs)
      were detected using ELISA, in concentrations ranging from 3.9 to 108 MUg L-1,
      from 0.3 to 2.8 MUg L-1 and from 0.4 to 1.2 MUg L-1, respectively. In half of the
      samples examined more than one cyanotoxins were detected. Our results document
      the first report on the occurrence of CYN and STX in freshwaters of Greece and
      show that potential STX producers are Cylindrospermopsis raciborskii and
      Aphanizomenon flos-aquae. Further studies are needed to assess potential CYN
      producers. This study provides further data on the distribution and toxicity of
      C. raciborskii and Aph. flos-aquae and documents a C. raciborskii dominated bloom
      producing STX in Europe.

PMID- 24275085
TI  - Effect of mindfulness meditation on brain-computer interface performance.
AB  - Electroencephalogram based brain-computer interfaces (BCIs) enable stroke and
      motor neuron disease patients to communicate and control devices. Mindfulness
      meditation has been claimed to enhance metacognitive regulation. The current
      study explores whether mindfulness meditation training can thus improve the
      performance of BCI users. To eliminate the possibility of expectation of
      improvement influencing the results, we introduced a music training condition. A
      norming study found that both meditation and music interventions elicited clear
      expectations for improvement on the BCI task, with the strength of expectation
      being closely matched. In the main 12 week intervention study, seventy-six
      healthy volunteers were randomly assigned to three groups: a meditation training
      group; a music training group; and a no treatment control group. The mindfulness
      meditation training group obtained a significantly higher BCI accuracy compared
      to both the music training and no-treatment control groups after the
      intervention, indicating effects of meditation above and beyond expectancy
      effects.

PMID- 24275086
TI  - Oxidative stress and photoinhibition can be separated in the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Roles of oxidative stress and photoinhibition in high light acclimation were
      studied using a regulatory mutant of the cyanobacterium Synechocystis sp. PCC
      6803. The mutant strain DeltasigCDE contains the stress responsive SigB as the
      only functional group 2 sigma factor. The ?sigCDE strain grew more slowly than
      the control strain in methyl-viologen-induced oxidative stress. Furthermore, a
      fluorescence dye detecting H2O2, hydroxyl and peroxyl radicals and peroxynitrite,
      produced a stronger signal in ?sigCDE than in the control strain, and
      immunological detection of carbonylated residues showed more protein oxidation in
      ?sigCDE than in the control strain. These results indicate that ?sigCDE suffers
      from oxidative stress in standard conditions. The oxidative stress may be
      explained by the findings that ?sigCDE had a low content of glutathione and low
      amount of Flv3 protein functioning in the Mehler-like reaction. Although ?sigCDE
      suffers from oxidative stress, up-regulation of photoprotective carotenoids and
      Flv4, Sll2018, Flv2 proteins protected PSII against light induced damage by
      quenching singlet oxygen more efficiently in ?sigCDE than in the control strain
      in visible and in UV-A/B light. However, in UV-C light singlet oxygen is not
      produced and PSII damage occurred similarly in the ?sigCDE and control strains.
      According to our results, resistance against the light-induced damage of PSII
      alone does not lead to high light tolerance of the cells, but in addition
      efficient protection against oxidative stress would be required.

PMID- 24275087
TI  - Mitochondrial dismissal in mammals, from protein degradation to mitophagy.
AB  - Mitochondria are double-membraned highly dynamic organelles; the shape, location
      and function of which are determined by a constant balance between opposing
      fusion and fission events. A fine modulation of mitochondrial structure is
      crucial for their correct functionality and for many physiological cell
      processes, the status of these organelles, being thus a key aspect in a cell's
      fate. Indeed, the homeostasis of mitochondria needs to be highly regulated for
      the above mentioned reasons, and since a) they are the major source of energy; b)
      they participate in various signaling pathways; albeit at the same time c) they
      are also the major source of reactive oxygen species (ROS, the main damaging
      detrimental players for all cell components). Elaborate mechanisms of
      mitochondrial quality control have evolved for maintaining a functional
      mitochondrial network and avoiding cell damage. The first mechanism is the
      removal of damaged mitochondrial proteins within the organelle via chaperones and
      protease; the second is the cytosolic ubiquitin-proteasome system (UPS), able to
      eliminate proteins embedded in the outer mitochondrial membrane; the third is the
      removal of the entire mitochondria through mitophagy, in the case of extensive
      organelle damage and dysfunction. In this review, we provide an overview of these
      mitochondria stability and quality control mechanisms, highlighting mitophagy,
      and emphasizing the central role of mitochondrial dynamics in this context. This
      article is part of a Special Issue entitled: Dynamic and ultrastructure of
      bioenergetic membranes and their components. 

PMID- 24275088
TI  - Prevention of rat liver fibrosis and carcinogenesis by coffee and caffeine.
AB  - Coffee has been inversely related to the incidence of human liver disease;
      however, whether caffeine is the component responsible for the beneficial effects
      of coffee remains controversial. This study evaluated the beneficial effects of
      coffee or caffeine in a medium-term bioassay for rat liver
      fibrosis/carcinogenesis induced by diethylnitrosamine (DEN) and carbon
      tetrachloride (CCl4). One week after the DEN injection, the groups started to
      receive conventional coffee, instant coffee or 0.1% caffeine ad libitum for 24
      weeks. The groups receiving conventional coffee or caffeine presented a
      significant reduction in collagen content and mRNA expression of collagen I. The
      groups receiving instant coffee or caffeine had a significant reduction in the
      size and area of pre-neoplastic lesions and in the mean number of neoplastic
      lesions. A significant increase in liver bax protein levels was observed in the
      groups receiving instant coffee or caffeine as compared to the control group.
      These data indicate that the most pronounced hepatoprotective effect against
      fibrosis was observed in the groups receiving conventional coffee and 0.1%
      caffeine, and the greatest effects against liver carcinogenesis were detected in
      the groups receiving instant coffee and 0.1% caffeine.

PMID- 24275089
TI  - Monascin and ankaflavin act as natural AMPK activators with PPARalpha agonist
      activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed
      C57BL/6 mice.
AB  - Yellow pigments monascin (MS) and ankaflavin (AK) are secondary metabolites
      derived from Monascus-fermented products. The hypolipidemic and anti-inflammatory
      effects of MS and AK indicate that they have potential on preventing or curing
      nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) and high-fat diet were
      used to induce steatosis in FL83B hepatocytes and NAFLD in mice, respectively. We
      found that both MS and AK prevented fatty acid accumulation in hepatocytes by
      inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid beta
      oxidation mediated by activating peroxisome proliferator-activated receptor
      (PPAR)-alpha and AMP-activated kinase (AMPK). Furthermore, MS and AK
      significantly attenuated high-fat diet-induced elevation of total cholesterol
      (TC), triaceylglycerol (TG), free fatty acid (FFA), and low density lipoprotein
      cholesterol (LDL-C) in plasma. MS and AK promoted AMPK phosphorylation,
      suppressed the steatosis-related mRNA expression and inflammatory cytokines
      secretion, as well as upregulated farnesoid X receptor (FXR), peroxisome
      proliferator-activated receptor gamma co-activator (PGC)-1alpha, and PPARalpha
      expression to induce fatty acid oxidation in the liver of mice. We provided
      evidence that MS and AK act as PPARalpha agonists to upregulate AMPK activity and
      attenuate NAFLD. MS and AK may be supplied in food supplements or developed as
      functional foods to reduce the risk of diabetes and obesity. 

PMID- 24275090
TI  - Bioactivity assessment and toxicity of crocin: a comprehensive review.
AB  - Since ancient times, saffron, the dried stigma of the plant Crocus sativus L. has
      been extensively used as a spice and food colorant; in folk medicine it has been
      reputed to be efficacious for the alleviation and treatment of ailments. In
      addition to the three founded major constituents including crocin, picrocrocin
      and safranal, presence of carotenoids, carbohydrates, proteins, anthocyanins,
      vitamins and minerals provide valuable insights into the health benefits and
      nutritional value of saffron. Of the carotenoids present in saffron, highly water
      soluble crocin (mono and diglycosyl esters of a polyene dicarboxylic acid, named
      crocetin) is responsible for the majority of its color, and appears to possess
      various health-promoting properties, as an antioxidant, antitumor, memory
      enhancer, antidepressant, anxiolytic and aphrodisiac. It is also worth noting
      that the crocin principle of saffron exhibited high efficacy along with no major
      toxicity in experimental models. We would be remiss to not consider the great
      potential of saffron and crocin, which benefits the cuisine and health of human
      life throughout the world. The present study provides a comprehensive and updated
      report of empirical investigations on bioactivities and biological
      characteristics of crocin. 

PMID- 24275091
TI  - Dual inhibition of Src family kinases and Aurora kinases by SU6656 modulates CTGF
      (connective tissue growth factor) expression in an ERK-dependent manner.
AB  - Src kinases are regulators of the expression of connective tissue growth factor
      (CTGF/CCN2), which plays a role in fibrotic injuries. The aim of the present
      study was to evaluate the potential of SU6656, a dual inhibitor of Src family and
      Aurora kinases, to interfere with the synthesis of this pro-fibrotic factor.
      SU6656 impaired TGF-beta-mediated upregulation of CTGF mRNA and protein in
      proximal epithelial HKC-8 cells, and also reduced CTGF expression in cells
      exposed to autocrine growth factors. In association with the inhibition of Src
      family kinases and diminished focal adhesion kinase activity, adherence of the
      cells was reduced. Furthermore, SU6656 interfered with Aurora kinase activity
      resulting in inhibition of cell division and formation multilobular nuclei after
      24h. Comparable alterations were observed in primary tubular cells. When cell
      division was inhibited by SU6656 or ZM447439, a specific inhibitor of Aurora
      kinases, CTGF levels were back to control or even increased after 48h. The
      activity of RhoA-Rho kinase and ERK signaling was analyzed to delineate the
      signaling pathways responsible for the biphasic regulation of CTGF. While Rho
      kinase was not significantly altered by SU6656, ERK activity was inhibited in the
      early phase and increased after 24-48h. ERK activity correlated with secreted
      CTGF. As ZM447439 increased ERK activity only after 48h, cellular reorganization
      is likely responsible for triggering the ERK-dependent upregulation of CTGF.
      Taken together, in non-transformed epithelial cells, SU6656 modulates the
      expression of the pro-fibrotic factor CTGF in a time-dependent manner by
      inhibition of Src kinases and Aurora kinases. 

PMID- 24275092
TI  - Podoplanin is a substrate of presenilin-1/gamma-secretase.
AB  - Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an
      important role in development and cancer. Here, we provide evidence that the
      intracellular domain (ICD) of podoplanin is released into the cytosol following a
      sequential proteolytic processing by a metalloprotease and gamma-secretase.
      Western blotting and cell fractionation studies revealed that HEK293T and MDCK
      cells transfected with an eGFP-tagged podoplanin construct (PDPNeGFP, 50-63kDa)
      constitutively express two C-terminal fragments (CTFs): a ~33kDa membrane-bound
      PCTF33, and a ~29kDa cytosolic podoplanin ICD (PICD). While pharmacological
      inhibition of metalloproteases reduced the expression of PCTF33, treatment of
      cells with gamma-secretase inhibitors resulted in enhanced PCTF33 levels. PCTF33
      processing by gamma-secretase depends on presenilin-1 (PS1) function: cells
      expressing a dominant negative form of PS1 (PS1 D385N), and mouse embryonic
      fibroblasts (MEFs) genetically deficient in PS1, but not in PS2, show higher
      levels of PCTF33 expression with respect to wild-type MEFs. Furthermore,
      transfection of PS1 deficient MEFs with wild-type PS1 (PS1 wt) decreased PCTF33
      levels. N-terminal amino acid sequencing of the affinity purified PICD revealed
      that the gamma-secretase cleavage site was located between valines 150 and 151,
      but these residues are not critical for proteolysis. We found that podoplanin
      CTFs are also generated in cells expressing podoplanin mutants harboring
      heterologous transmembrane regions. Taken together, these results indicate that
      podoplanin is a novel substrate for PS1/gamma-secretase. 

PMID- 24275093
TI  - AP2alpha transcriptional activity is essential for retinoid-induced neuronal
      differentiation of mesenchymal stem cells.
AB  - Pre-activation of the retinoid signaling pathway by all-trans retinoic acid
      facilitates neuronal differentiation of mesenchymal stem cells. Using protein/DNA
      based screening assays, we identified activator protein 2alpha as an important
      downstream target of all-trans retinoic acid. Although all-trans retinoic acid
      treatment significantly increased activator protein 2alpha transcriptional
      activity, it did not affect its expression. Inhibition of activator protein
      2alpha with dominant-negative mutants reduced ATRA-induced differentiation of
      mesenchymal stem cells into neurons and reversed its associated functional
      recovery of memory impairment in the cell-based treatment of a hypoxic-ischemic
      brain damage rat model. Dominant-negative mutants of activator protein 2alpha
      inhibited the expression of neuronal markers which were induced by retinoic acid
      receptor beta activation. All-trans retinoic acid treatment increased
      phosphorylation of activator protein 2alpha and resulted in its nuclear
      translocation. This was blocked by siRNA-mediated knockdown of retinoic acid
      receptor beta. Furthermore, we found that retinoic acid receptor beta directly
      interacted with activator protein 2alpha. In summary, the regulation of all-trans
      retinoic acid on activator protein 2alpha transcriptional activity was mediated
      by activation of retinoic acid receptor beta and subsequent phosphorylation and
      nuclear translocation of activator protein 2alpha. Our results strongly suggest
      that activator protein 2alpha transcriptional activity is essential for all-trans
      retinoic acid-induced neuronal differentiation of mesenchymal stem cells. 

PMID- 24275094
TI  - The anti-atherogenic cytokine interleukin-33 inhibits the expression of a
      disintegrin and metalloproteinase with thrombospondin motifs-1, -4 and -5 in
      human macrophages: Requirement of extracellular signal-regulated kinase, c-Jun N
      terminal kinase and phosphoinositide 3-kinase signaling pathways.
AB  - Atherosclerosis is an inflammatory disorder of the vasculature regulated by
      cytokines. Amongst the cytokines, IL-33 attenuates the development of
      atherosclerosis in mouse model systems via several mechanisms, including
      inhibition of macrophage foam cell formation and promotion of a Th1 to Th2 shift.
      Proteases produced by macrophages, such as matrix metalloproteinases and members
      of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)
      family, play potential roles in regulating atherosclerotic plaque stability.
      Despite such importance, the action of IL-33 on the expression of such proteases
      has not been analyzed. We have therefore investigated the effect of IL-33 on the
      expression of ADAMTS-1, -4 and -5 in human macrophages. Immunohistochemical
      analysis showed that these three proteases were expressed in human
      atherosclerotic lesions, particularly by macrophages and, to a lesser extent, by
      smooth muscle cells and endothelial cells. The expression of ADAMTS-1, -4 and -5
      in human macrophages was specifically inhibited by IL-33. The action of IL-33 on
      the expression of these ADAMTS members was mediated through its receptor ST2. IL
      33 activated ERK1/2, JNK1/2 and c-Jun, but not p38 MAPK or Akt, in human
      macrophages. RNA interference assays using a combination of adenoviral encoding
      small hairpin RNA and small interfering RNA showed a requirement of ERK1/2,
      JNK1/2, c-Jun, PI3Kgamma and PI3Kdelta, but not p38alpha, in the IL-33-inhibited
      expression of these ADAMTS isoforms. These studies provide novel insights into
      the expression of ADAMTS-1, -4 and -5 in human atherosclerotic lesions and the
      regulation of their expression in human macrophages by the key anti-atherogenic
      cytokine IL-33. 

PMID- 24275095
TI  - Syndecan-4 inhibits Wnt/beta-catenin signaling through regulation of low-density
      lipoprotein receptor-related protein (LRP6) and R-spondin 3.
AB  - Regulation of Wnt signaling is crucial for embryonic development and adult
      homeostasis. Here we study the role of Syndecan-4 (SDC4), a cell-surface heparan
      sulphate proteoglycan, and Fibronectin (FN), in Wnt/beta-catenin signaling. Gain-
      and loss-of-function experiments in mammalian cell lines and Xenopus embryos
      demonstrate that SDC4 and FN inhibit Wnt/beta-catenin signaling. Epistatic and
      biochemical experiments show that this inhibition occurs at the cell membrane
      level through regulation of LRP6. R-spondin 3, a ligand that promotes canonical
      and non-canonical Wnt signaling, is more prone to potentiate Wnt/beta-catenin
      signaling when SDC4 levels are reduced, suggesting a model whereby SDC4 tunes the
      ability of R-spondin to modulate the different Wnt signaling pathways. Since SDC4
      has been previously related to non-canonical Wnt signaling, our results also
      suggest that this proteoglycan can be a key component in the regulation of Wnt
      signaling. 

PMID- 24275096
TI  - Making surrogate beta-cells from mesenchymal stromal cells: perspectives and
      future endeavors.
AB  - Generation of surrogate beta-cells is the need of the day to compensate the short
      supply of islets for transplantation to diabetic patients requiring daily shots
      of insulin. Over the years several sources of stem cells have been claimed to
      cater to the need of insulin producing cells. These include human embryonic stem
      cells, induced pluripotent stem cells, human perinatal tissues such as amnion,
      placenta, umbilical cord and postnatal tissues involving adipose tissue, bone
      marrow, blood monocytes, cord blood, dental pulp, endometrium, liver, labia
      minora dermis-derived fibroblasts and pancreas. Despite the availability of such
      heterogonous sources, there is no substantial breakthrough in selecting and
      implementing an ideal source for generating large number of stable insulin
      producing cells. Although the progress in derivation of beta-cell like cells from
      embryonic stem cells has taken a greater leap, their application is limited due
      to controversy surrounding the destruction of human embryo and immune rejection.
      Since multipotent mesenchymal stromal cells are free of ethical and immunological
      complications, they could provide unprecedented opportunity as starting material
      to derive insulin secreting cells. The main focus of this review is to discuss
      the merits and demerits of MSCs obtained from human peri- and post-natal tissue
      sources to yield abundant glucose responsive insulin producing cells as ideal
      candidates for prospective stem cell therapy to treat diabetes. 

PMID- 24275097
TI  - GPER activates Notch signaling in breast cancer cells and cancer-associated
      fibroblasts (CAFs).
AB  - The G protein-coupled receptor GPR30/GPER has been shown to mediate rapid effects
      of 17beta-estradiol (E2) in diverse types of cancer cells. Here, we provide
      evidence for a novel crosstalk between GPER and the Notch signaling pathway in
      breast cancer cells and cancer-associated fibroblasts (CAFs). We show that E2 and
      the GPER selective ligand G-1 induce both the gamma-secretase-dependent
      activation of Notch-1 and the expression of the Notch target gene Hes-1. These
      inductions are prevented by knocking down GPER or by using a dominant-negative
      mutant of the Notch transcriptional co-activator Master-mind like-1 (DN-MAML-1),
      hence suggesting the involvement of GPER in the Notch-dependent transcription. By
      performing chromatin-immunoprecipitation experiments and luciferase assays, we
      also demonstrate that E2 and G-1 induce the recruitment of the intracellular
      domain of Notch-1 (N1ICD) to the Hes-1 promoter and the transactivation of a Hes
      1-reporter gene, respectively. Functionally, the E2 and G-1-induced migration of
      breast cancer cells and CAFs is abolished in presence of the gamma-secretase
      inhibitor GSI or DN-MAML-1, which both inhibit the Notch signaling pathway. In
      addition, we demonstrate that E2 and G-1 prevent the expression of VE-Cadherin,
      while both compounds induce the expression of Snail, a Notch target gene acting
      as a repressor of cadherins expression. Notably, both GSI and DN-MAML-1 abolish
      the up-regulation of Snail-1 by E2 and G-1, whereas the use of GSI rescues VE
      Cadherin expression. Taken together, our results prove the involvement of the
      Notch signaling pathway in mediating the effects of estrogenic GPER signaling in
      breast cancer cells and CAFs. 

PMID- 24275098
TI  - Relative bioavailability of a paediatric granule formulation of the HIV integrase
      inhibitor dolutegravir in healthy adult subjects.
AB  - BACKGROUND: This study evaluated the pharmacokinetics of a granule formulation of
      dolutegravir developed as an alternative to tablets for use in paediatric
      populations. METHODS: A randomized, open-label study in healthy adults was
      carried out. Subjects received five treatments in a crossover design: a single
      dose of dolutegravir 50 mg as a tablet and dolutegravir 50 mg in 10 g of granule
      administered directly to mouth or mixed with purified water, water containing
      high cation concentrations or milk-based infant formula. Study treatments were
      separated by 7 days. Safety evaluations and serial pharmacokinetic sampling were
      done during each treatment period. A non-compartmental pharmacokinetic analysis
      was performed; geometric least-squares mean ratios and 90% CIs were generated for
      treatment comparison. Palatability was assessed by questionnaire. RESULTS: Plasma
      dolutegravir exposures in all granule treatment arms exceeded those of tablet
      formulation. The mean area under the curve from time 0 to infinity (AUC(0
      infinity)) and maximum concentrations were 55-83% and 62-102% higher,
      respectively. Pharmacokinetics were similar when dolutegravir was mixed with
      purified or cation-containing water. Dolutegravir was well tolerated, with no
      withdrawals due to adverse events. Taste was rated acceptable for all treatments.
      CONCLUSIONS: The exposure of dolutegravir after administration of granule
      formulation alone, with different types of water and with milk formula, exceeded
      that of the tablet. The similarity of dolutegravir exposure seen with the granule
      formulation demonstrates that dolutegravir granule can be given without
      restriction on the type of liquid or can be administered directly to the mouth
      (for example, when potable water is not available).

PMID- 24275099
TI  - Inhibition of Binding of beta2-Glycoprotein 1 to Phosphatidylserine by Polymyxin
      B, a Lupus-Like Anticoagulant.
AB  - Polymyxin B is a cationic peptide that inhibits phospholipid-dependent
      coagulation tests including activated partial thromboplastin time and to a lesser
      degree prothrombin time. Thrombin clotting time is insensitive to polymyxin B.
      beta2-glycoprotein 1 (beta2GP1) is a cofactor of antiphospholipid antibodies.
      Antiphospholipid autoantibodies also poses lupus anticoagulant activity through
      interactions with beta2GP1. Using affinity chromatography, polymyxin B can
      effectively decrease the binding of beta2GP1 to immobilize phosphatidylserine.
      Since then, anticoagulant effect of polymyxin B is most likely due to the binding
      to negatively charged phospholipids, preventing formation of coagulation
      complexes. 

PMID- 24275100
TI  - Exopolyphosphatase of Pseudomonas aeruginosa is essential for the production of
      virulence factors, and its expression is controlled by NtrC and PhoB acting at
      two interspaced promoters.
AB  - The exopolyphosphatase (Ppx) of Pseudomonas aeruginosa is encoded by the PA5241
      gene (ppx). Ppx catalyses the hydrolysis of inorganic polyphosphates to
      orthophosphate (Pi). In the present work, we identified and characterized the
      promoter region of ppx and its regulation under environmental stress conditions.
      The role of Ppx in the production of several virulence factors was demonstrated
      through studies performed on a ppx null mutant. We found that ppx is under the
      control of two interspaced promoters, dually regulated by nitrogen and phosphate
      limitation. Under nitrogen-limiting conditions, its expression was controlled
      from a sigma(54)-dependent promoter activated by the response regulator NtrC.
      However, under Pi limitation, the expression was controlled from a sigma(70)
      promoter, activated by PhoB. Results obtained from the ppx null mutant
      demonstrated that Ppx is involved in the production of virulence factors
      associated with both acute infection (e.g. motility-promoting factors, blue/green
      pigment production, C6-C12 quorum-sensing homoserine lactones) and chronic
      infection (e.g. rhamnolipids, biofilm formation). Molecular and physiological
      approaches used in this study indicated that P. aeruginosa maintains consistently
      proper levels of Ppx regardless of environmental conditions. The precise control
      of ppx expression appeared to be essential for the survival of P. aeruginosa and
      the occurrence of either acute or chronic infection in the host. 

PMID- 24275101
TI  - Identification of the immunoproteome of the meningococcus by cell surface
      immunoprecipitation and MS.
AB  - Most healthy adults are protected from meningococcal disease by the presence of
      naturally acquired anti-meningococcal antibodies; however, the identity of the
      target antigens of this protective immunity remains unclear, particularly for
      protection against serogroup B disease. To identify the protein targets of
      natural protective immunity we developed an immunoprecipitation and proteomics
      approach to define the immunoproteome of the meningococcus. Sera from 10 healthy
      individuals showing serum bactericidal activity against both a meningococcal C
      strain (L91543) and the B strain MC58, together with commercially available
      pooled human sera, were used as probe antisera. Immunoprecipitation was performed
      with each serum sample and live cells from both meningococcal strains.
      Immunoprecipitated proteins were identified by MS. Analysis of the immunoproteome
      from each serum demonstrated both pan-reactive antigens that were recognized by
      most sera as well as subject-specific antigens. Most antigens were found in both
      meningococcal strains, but a few were strain-specific. Many of the
      immunoprecipitated proteins have been characterized previously as surface
      antigens, including adhesins and proteases, several of which have been recognized
      as vaccine candidate antigens, e.g. factor H-binding protein, NadA and neisserial
      heparin-binding antigen. The data demonstrate clearly the presence of
      meningococcal antibodies in healthy individuals with no history of meningococcal
      infection and a wide diversity of immune responses. The identification of the
      immunoreactive proteins of the meningococcus provides a basis for understanding
      the role of each antigen in the natural immunity associated with carriage and may
      help to design vaccination strategies. 

PMID- 24275102
TI  - A 2D gel electrophoresis-based snapshot of the phosphoproteome in the
      cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - Cyanobacteria are photoautotrophic prokaryotes that occur in highly variable
      environments. Protein phosphorylation is one of the most widespread means to
      adjust cell metabolism and gene expression to the demands of changing growth
      conditions. Using a 2D gel electrophoresis-based approach and a phosphoprotein
      specific dye, we investigated the protein phosphorylation pattern in cells of the
      model cyanobacterium Synechocystis sp. strain PCC 6803. The comparison of gels
      stained for total and phosphorylated proteins revealed that approximately 5 % of
      the protein spots seemed to be phosphoproteins, from which 32 were identified
      using MALDI-TOF MS. For eight of them the phosphorylated amino acid residues were
      mapped by subsequent mass spectrometric investigations of isolated
      phosphopeptides. Among the phosphoproteins, we found regulatory proteins, mostly
      putative anti-sigma factor antagonists, and proteins involved in translation.
      Moreover, a number of enzymes catalysing steps in glycolysis or the Calvin-Benson
      cycle were found to be phosphorylated, implying that protein phosphorylation
      might represent an important mechanism for the regulation of the primary carbon
      metabolism in cyanobacterial cells. 

PMID- 24275103
TI  - Patterns and trends in insulin intensification among patients with type 2
      diabetes: a systematic review.
AB  - Type 2 diabetes (T2DM) diagnoses are skyrocketing, making treatment of this
      disease an increasing focus of primary care visits. Guidelines recommend insulin
      intensification over time to achieve HbA1c targets. We conducted a systematic
      review regarding patterns and trends of insulin intensification and barriers to
      intensification. Providers across primary and specialty care settings often did
      not intensify insulin regimens despite patients' clinical status. Even among
      progressed patients, HbA1c values remained high. The paucity of available studies
      prevented a comprehensive understanding of patterns and trends in insulin
      intensification. Such information is needed to assess the quality of
      pharmacologic care for patients with T2DM. 

PMID- 24275104
TI  - Impact of clinical inertia on cardiovascular risk factors in patients with
      diabetes.
AB  - AIMS: To determine whether clinical inertia is associated with simpler
      interventions occurring more often than complex changes and the association
      between clinical inertia and outcomes. METHODS: Prevalence of clinical inertia
      over a 30 month period for hyperglycaemia, hypertension and dyslipidaemia was
      calculated in a random sample (n=334) of patients attending a diabetes clinic.
      Comparisons between prevalence of clinical inertia and outcomes for each
      condition were examined using parametric tests of association. RESULTS: There was
      less clinical inertia in hyperglycaemia (29% of consultations) compared with LDL
      (80% of consultations) and systolic BP (68% of consultations). Consultations
      where therapy was intensified had a greater reduction in risk factor levels than
      when no change was made. No association was found between treatment intensity
      scores and changes in HbA1c, LDL or blood pressure over 30 months. CONCLUSIONS:
      Physicians are no more likely to intervene in conditions where simple therapeutic
      changes are necessary as opposed to complex changes. Greater clinical inertia
      leads to poorer outcomes. There continues to be substantial clinical inertia in
      routine clinical practice. Physicians should adopt a holistic approach to
      cardiovascular risk reduction in patients with diabetes, adhere more closely to
      established management guidelines and emphasize personal individualized target
      setting.

PMID- 24275105
TI  - Structural, electronic and magnetic properties of binary transition metal
      aluminum clusters: absence of electronic shell structure.
AB  - Single Cr, Mn, Fe, Co and Ni doped Al clusters having up to 12 Al atoms are
      studied using density functional methods. The global minima of structure for all
      the clusters are identified, and their relative stability and electronic and
      magnetic properties are studied. FeAl4 and CoAl3 are found to have enhanced
      stability and aromatic behavior. In contrast to binary transition metal alkali
      and transition metal alkaline earth clusters, spherical shell models cannot
      describe the electronic structure of transition metal aluminum clusters. 

PMID- 24275106
TI  - Enhanced anaerobic digestion of waste activated sludge digestion by the addition
      of zero valent iron.
AB  - Anaerobic digestion is promising technology to recover energy from waste
      activated sludge. However, the sludge digestion is limited by its low efficiency
      of hydrolysis-acidification. Zero valent iron (ZVI) as a reducing material is
      expected to enhance anaerobic process including the hydrolysis-acidification
      process. Considering that, ZVI was added into an anaerobic sludge digestion
      system to accelerate the sludge digestion in this study. The results indicated
      that ZVI effectively enhanced the decomposition of protein and cellulose, the two
      main components of the sludge. Compared to the control test without ZVI, the
      degradation of protein increased 21.9% and the volatile fatty acids production
      increased 37.3% with adding ZVI. More acetate and less propionate are found
      during the hydrolysis-acidification with ZVI. The activities of several key
      enzymes in the hydrolysis and acidification increased 0.6-1 time. ZVI made the
      methane production raise 43.5% and sludge reduction ratio increase 12.2 percent
      points. Fluorescence in situ hybridization analysis showed that the abundances of
      hydrogen-consuming microorganisms including homoacetogens and hydrogenotrophic
      methanogens with ZVI were higher than the control, which reduced the H2
      accumulation to create a beneficial condition for the sludge digestion in
      thermodynamics. 

PMID- 24275107
TI  - A three-step test of phosphate sorption efficiency of potential agricultural
      drainage filter materials.
AB  - Phosphorus (P) eutrophication of lakes and streams, coming from drained
      farmlands, is a serious problem in areas with intensive agriculture. Installation
      of P sorbing filters at drain outlets may be a solution. Efficient sorbents to be
      used for such filters must possess high P bonding affinity to retain ortho
      phosphate (Pi) at low concentrations. In addition high P sorption capacity, fast
      bonding and low desorption is necessary. In this study five potential filter
      materials (Filtralite-P((r)), limestone, calcinated diatomaceous earth, shell
      sand and iron-oxide based CFH) in four particle size intervals were investigated
      under field relevant P concentrations (0-161 MUM) and retentions times of 0-24
      min. Of the five materials examined, the results from P sorption and desorption
      studies clearly demonstrate that the iron based CFH is superior as a filter
      material compared to calcium based materials when tested against criteria for
      sorption affinity, capacity and stability. The finest CFH and Filtralite-P((r))
      fractions (0.05-0.5 mm) were best with P retention of >=90% of Pi from an initial
      concentration of 161 MUM corresponding to 14.5 mmol/kg sorbed within 24 min. They
      were further capable to retain >=90% of Pi from an initially 16 MUM solution
      within 11/2 min. However, only the finest CFH fraction was also able to retain
      >=90% of Pi sorbed from the 16 MUM solution against 4 times desorption sequences
      with 6 mM KNO3. Among the materials investigated, the finest CFH fraction is
      therefore the only suitable filter material, when very fast and strong bonding of
      high Pi concentrations is needed, e.g. in drains under P rich soils during
      extreme weather conditions. 

PMID- 24275108
TI  - The accumulation of radioactive contaminants in drinking water distribution
      systems.
AB  - The accumulation of trace contaminants in drinking water distribution system
      sediment and scales has been documented, raising concerns that the subsequent
      release of the contaminants back to the water is a potential human exposure
      pathway. Radioactive contaminants are of concern because of their known health
      effects and because of their persistence within associated distribution system
      materials. The objective of this work was to measure the amount of a number of
      radioactive contaminants (radium, thorium, and uranium isotopes, and gross alpha
      and beta activity) in distribution solids collected from water systems in four
      states (Wisconsin, Illinois, Minnesota, and Texas). The water utilities chosen
      had measurable levels of radium in their source waters. In addition, 19 other
      elements in the solids were quantified. Water systems provided solids primarily
      collected during routine fire hydrant flushing. Iron was the dominant element in
      nearly all of the solids and was followed by calcium, phosphorus, magnesium,
      manganese, silicon, aluminum and barium in descending order. Gross alpha and beta
      radiation averaged 255 and 181 pCi/g, and were as high as 1602 and 1169 pCi/g,
      respectively. Total radium, thorium and uranium averaged 143, 40 and 6.4 pCi/g,
      respectively. Radium-226 and -228 averaged 74 and 69 pCi/g, and were as high as
      250 and 351 pCi/g, respectively. 

PMID- 24275109
TI  - Treatment of poly- and perfluoroalkyl substances in U.S. full-scale water
      treatment systems.
AB  - The near ubiquitous presence of poly- and perfluoroalkyl substances (PFASs) in
      humans has raised concerns about potential human health effects from these
      chemicals, some of which are both extremely persistent and bioaccumulative.
      Because some of these chemicals are highly water soluble, one major pathway for
      human exposure is the consumption of contaminated drinking water. This study
      measured concentrations of PFASs in 18 raw drinking water sources and 2 treated
      wastewater effluents and evaluated 15 full-scale treatment systems for the
      attenuation of PFASs in water treatment utilities throughout the U.S. A liquid
      chromatography tandem mass-spectrometry method was used to enable measurement of
      a suite of 23 PFASs, including perfluorocarboxylic acids (PFCAs) and
      perfluorosulfonic acids (PFSAs). Despite the differences in reporting levels, the
      PFASs that were detected in >70% of the source water samples (n = 39) included
      PFSAs, perfluorobutane sulfonic acid (74%), perfluorohexane sulfonic acid (79%),
      and perfluorooctane sulfonic acid (84%), and PFCAs, perfluoropentanoic acid
      (74%), perfluorohexanoic acid (79%), perfluoroheptanoic acid (74%), and
      perfluorooctanoic acid (74%). More importantly, water treatment techniques such
      as ferric or alum coagulation, granular/micro-/ultra- filtration, aeration,
      oxidation (i.e., permanganate, ultraviolet/hydrogen peroxide), and disinfection
      (i.e., ozonation, chlorine dioxide, chlorination, and chloramination) were mostly
      ineffective in removing PFASs. However, anion exchange and granular activated
      carbon treatment preferably removed longer-chain PFASs and the PFSAs compared to
      the PFCAs, and reverse osmosis demonstrated significant removal for all the
      PFASs, including the smallest PFAS, perfluorobutanoic acid. 

PMID- 24275110
TI  - Sorption and biodegradation of organic micropollutants during river bank
      filtration: a laboratory column study.
AB  - This study investigated sorption and biodegradation behaviour of 14 organic
      micropollutants (OMP) in soil columns representative of the first metre (oxic
      conditions) of the river bank filtration (RBF) process. Breakthrough curves were
      modelled to differentiate between OMP sorption and biodegradation. The main
      objective of this study was to investigate if the OMP biodegradation rate could
      be related to the physico-chemical properties (charge, hydrophobicity and
      molecular weight) or functional groups of the OMPs. Although trends were observed
      between charge or hydrophobicity and the biodegradation rate for charged
      compounds, a statistically significant linear relationship for the complete OMP
      mixture could not be obtained using these physico-chemical properties. However, a
      statistically significant relationship was obtained between biological
      degradation rates and the OMP functional groups. The presence of ethers and
      carbonyl groups will increase biodegradability, while the presence of amines,
      ring structures, aliphatic ethers and sulphur will decrease biodegradability.
      This predictive model based on functional groups can be used by drinking water
      companies to make a first estimate whether a newly detected compound will be
      biodegraded during the first metre of RBF or that additional treatment is
      required. In addition, the influence of active and inactive biomass
      (biosorption), sand grains and the water matrix on OMP sorption was found to be
      negligible under the conditions investigated in this study. Retardation factors
      for most compounds were close to 1, indicating mobile behaviour of these
      compounds during soil passage. Adaptation of the biomass towards the dosed OMPs
      was not observed for a 6 month period, implying that new developed RBF sites
      might not be able to biodegrade compounds such as atrazine and sulfamethoxazole
      in the first few months of operation. 

PMID- 24275111
TI  - Kinetics of dechlorination by Dehalococcoides mccartyi using different carbon
      sources.
AB  - Stimulated anaerobic dechlorination is generally considered a valuable step for
      the remediation of aquifers polluted with chlorinated ethenes (CEs). Correct
      simulation and prediction of this process in situ, however, require good
      knowledge of the associated biological reactions. The aim of this study was to
      evaluate the dechlorination reaction in an aquifer contaminated with
      trichloroethene (TCE) and its daughter products, discharging into the Zenne
      River. Different carbon sources were used in batch cultures and these were
      related to the dechlorination reaction, together with the monitored biomarkers.
      Appropriate kinetic formulations were assessed. Reductive dechlorination of TCE
      took place only when external carbon sources were added to microcosms, and
      occurred concomitant with a pronounced increase in the Dehalococcoides mccartyi
      cell count as determined by 16S rRNA gene-targeted qPCR. This indicates that
      native dechlorinating bacteria are present in the aquifer of the Zenne site and
      that the oligotrophic nature of the aquifer prevents a complete degradation to
      ethene. The type of carbon source, the cell number of D. mccartyi or the
      reductive dehalogenase genes, however, did not unequivocally explain the observed
      differences in degradation rates or the extent of dechlorination. Neither first
      order, Michaelis-Menten nor Monod kinetics could perfectly simulate the
      dechlorination reactions in TCE spiked microcosms. A sensitivity analysis
      indicated that the inclusion of donor limitation would not significantly enhance
      the simulations without a clear process understanding. Results point to the role
      of the supporting microbial community but it remains to be verified how the
      complexity of the microbial (inter)actions should be represented in a model
      framework. 

PMID- 24275113
TI  - Acute urticaria presenting in the emergency room of a general hospital.
AB  - BACKGROUND: Acute urticaria is a common disorder that often prompts patients to
      seek treatment in the emergency room (ER). There are few data on acute urticaria
      presenting in ER. OBJECTIVES: This study aimed to provide demographic and
      clinical data of patients presenting with acute urticaria at an ER of an Italian
      general hospital covering an area of about 90,000 inhabitants. The predictive
      factors of the length of stay in the ER had also been investigated. METHODS: The
      database of ER patients was searched for urticaria by ICD-9 code and by keywords
      in the diagnosis description. All the medical records of the identified patients
      were reviewed and the length of stay in ER was noted. RESULTS: A total of 459
      patients were admitted to ER with acute urticaria in a 1-year period
      corresponding to 1.01% of total ER visits and to 1.2 admission per day.
      Angioedema was present in 139 cases (30.3%), fever in 55 (12%). Twenty-nine
      patients fulfilled the criteria of anaphylaxis. Triggers could be identified in
      193 cases (42%): drugs in 20.7%, insects bites (10.2%), foods (7.4%) and contact
      urticaria in 3.7%. Anaphylaxis (p<0.001), food (p<0.05) and drugs (p<0.05) as
      triggers were significant and independent predictive factors of the length of
      stay in ER. CONCLUSIONS: Patients with acute urticaria are frequently referred to
      the emergency room, but only in a few cases urticaria is associated with severe
      allergic manifestations. Drug and food hypersensitivity, together with
      anaphylaxis, are the best predictors of the length of stay in ER.

PMID- 24275115
TI  - Dissemination of carbapenemase-producing Enterobacteriaceae in France, 2012.
AB  - OBJECTIVES: Carbapenem-resistant Enterobacteriaceae isolates (n = 1485) were
      received at the French Associated National Reference Center for Antibiotic
      Resistance in 2012 and were characterized for their mechanism of resistance to
      carbapenems. METHODS: Carbapenemase production was detected using the biochemical
      based Carba NP test, based on the detection of in vitro hydrolysis of imipenem.
      All isolates with a positive Carba NP test result were characterized by PCR and
      sequencing. RESULTS: Carbapenemase production was identified in 23.1% of the
      isolates. The main carbapenemase type identified was OXA-48 and derivatives
      (75.5%). An overseas source was clearly demonstrated for only 27.6% of the
      isolates. CONCLUSIONS: OXA-48 and derivatives are now the most prevalent
      carbapenemases in France, with a possible spread of these producers in the
      community.

PMID- 24275114
TI  - Complete sequences of a novel blaNDM-1-harbouring plasmid from Providencia
      rettgeri and an FII-type plasmid from Klebsiella pneumoniae identified in Canada.
AB  - OBJECTIVES: Emergence of plasmids harbouring bla(NDM-1) is a major public health
      concern due to their association with multidrug resistance and their potential
      mobility. METHODS: PCR was used to detect bla(NDM-1) from clinical isolates of
      Providencia rettgeri (PR) and Klebsiella pneumoniae (KP). Antimicrobial
      susceptibilities were determined using Vitek 2. The complete DNA sequence of two
      bla(NDM-1) plasmids (pPrY2001 and pKp11-42) was obtained using a 454-Genome
      Sequencer FLX. Contig assembly and gap closures were confirmed by PCR-based
      sequencing. Comparative analysis was done using BLASTn and BLASTp algorithms.
      RESULTS: Both clinical isolates were resistant to all beta-lactams, carbapenems,
      aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole, and susceptible
      to tigecycline. Plasmid pPrY2001 (113 295 bp) was isolated from PR. It did not
      show significant homology to any known plasmid backbone and contained a truncated
      repA and novel repB. Two bla(NDM-1)-harbouring plasmids from Acinetobacter
      lwoffii (JQ001791 and JQ060896) shared 100% similarity to a 15 kb region that
      contained bla(NDM-1). pPrY2001 also contained a type II toxin/antitoxin system.
      pKp11-42 (146 695 bp) was isolated from KP. It contained multiple repA genes. The
      plasmid backbone had the highest homology to the IncFIIk plasmid type (51%
      coverage, 100% nucleotide identity). The bla(NDM-1) region was unique in that it
      was flanked upstream by IS3000 and downstream by a novel transposon designated
      Tn6229. pKp11-42 also contained a number of mutagenesis and plasmid stability
      proteins. CONCLUSIONS: pPrY2001 differed from all known plasmids due to its novel
      backbone and repB. pKp11-42 was similar to IncFIIk plasmids and contained a
      number of genes that aid in plasmid persistence.

PMID- 24275117
TI  - MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin.
AB  - OBJECTIVES: The aim of this study was to determine the MICs of 32 antimicrobial
      agents for 200 isolates of Rhodococcus equi of animal origin by applying a
      recently described broth microdilution protocol, and to investigate isolates with
      distinctly elevated rifampicin MICs for the genetic basis of rifampicin
      resistance. METHODS: The study included 200 R. equi isolates, including 160
      isolates from horses and 40 isolates from other animal sources, from the USA and
      Europe. MIC testing of 32 antimicrobial agents or combinations thereof followed a
      recently published protocol. A novel PCR protocol for the joint amplification of
      the three rpoB regions in which rifampicin resistance-mediating mutations have
      been reported was applied to isolates with elevated rifampicin MICs. The
      amplicons were sequenced and screened for mutations. RESULTS: Susceptibility
      testing revealed a rather uniform distribution of MICs for most of the
      antimicrobial agents tested. The lowest MICs were seen for clarithromycin,
      rifampicin and imipenem. Six isolates (3%) exhibited distinctly higher MICs of
      rifampicin than the remaining 194 isolates. In five of these six isolates, single
      bp exchanges, which resulted in the amino acid exchanges Gln513Leu, Asp516Val,
      His526Asp or Ser531Leu, were detected in the rifampicin resistance-determining
      region 1 of the rpoB gene, with Gln513Leu representing a novel substitution for
      R. equi. CONCLUSIONS: This study shows the MIC distribution of 32 antimicrobial
      agents for a large collection of R. equi isolates of animal origin from two
      continents. Isolates that exhibited distinctly elevated MICs of rifampicin were
      only rarely detected.

PMID- 24275116
TI  - An update to the HIV-TRePS system: the development of new computational models
      that do not require a genotype to predict HIV treatment outcomes.
AB  - OBJECTIVES: The optimal individualized selection of antiretroviral drugs in
      resource-limited settings is challenging because of the limited availability of
      drugs and genotyping. Here we describe the development of the latest
      computational models to predict the response to combination antiretroviral
      therapy without a genotype, for potential use in such settings. METHODS: Random
      forest models were trained to predict the probability of a virological response
      to therapy (<50 copies HIV RNA/mL) following virological failure using the
      following data from 22,567 treatment-change episodes including 1090 from southern
      Africa: baseline viral load and CD4 cell count, treatment history, drugs in the
      new regimen, time to follow-up and follow-up viral load. The models were assessed
      during cross-validation and with an independent global test set of 1000 cases
      including 100 from southern Africa. The models' accuracy [area under the receiver
      operating characteristic curve (AUC)] was evaluated and compared with genotyping
      using rules-based interpretation systems for those cases with genotypes
      available. RESULTS: The models achieved AUCs of 0.79-0.84 (mean 0.82) during
      cross-validation, 0.80 with the global test set and 0.78 with the southern
      African subset. The AUCs were significantly lower (0.56-0.57) for genotyping.
      CONCLUSIONS: The models predicted virological response to HIV therapy without a
      genotype as accurately as previous models that included a genotype. They were
      accurate for cases from southern Africa and significantly more accurate than
      genotyping. These models will be accessible via the online treatment support tool
      HIV-TRePS and have the potential to help optimize antiretroviral therapy in
      resource-limited settings where genotyping is not generally available.

PMID- 24275118
TI  - Efavirenz induces interactions between leucocytes and endothelium through the
      activation of Mac-1 and gp150,95.
AB  - OBJECTIVES: The potential cardiovascular (CV) toxicity associated with combined
      antiretroviral therapy (cART) has been attributed mainly to the nucleoside
      reverse transcriptase inhibitors abacavir and didanosine. However, the other two
      components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and
      protease inhibitors (PIs)--may also be implicated, either directly or by
      influencing the action of the other drugs. This study evaluates the acute direct
      effects of the NNRTIs efavirenz and nevirapine and one of the most widely
      employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV
      disease. METHODS: Drugs were analysed in vitro in human cells (interactions of
      peripheral blood polymorphonuclear or mononuclear cells with human umbilical vein
      endothelial cells) using a flow chamber system, and in vivo in rat mesenteric
      vessels by means of intravital microscopy. The expression of adhesion molecules
      in leucocytes and endothelial cells was studied by flow cytometry, and the role
      of these molecules in white cell recruitment was evaluated by pre-treating human
      cells or rats with blocking antibodies. RESULTS: Efavirenz and nevirapine, but
      not lopinavir, increased the rolling flux and adhesion of leucocytes in vitro and
      in vivo while inducing emigration in rat venules. Efavirenz, but not nevirapine,
      augmented the levels of CD11b, CD11c and CD18 in neutrophils and monocytes. The
      actions of efavirenz, but not of nevirapine, were reversed by antibodies against
      Mac-1 (CD11b/CD18), gp150,95 (CD11c/CD18) or ICAM-1 (CD54). CONCLUSIONS: NNRTIs,
      but not PIs, interfere with leucocyte-endothelial interactions. However,
      differences between efavirenz and nevirapine suggest a specific CV profile for
      each compound.

PMID- 24275119
TI  - A novel cell-based high-throughput screen for inhibitors of HIV-1 gene expression
      and budding identifies the cardiac glycosides.
AB  - OBJECTIVES: Highly active antiretroviral therapy (HAART) is the mainstay of
      treatment for HIV-1 infection. While current HAART regimens have been extremely
      effective, issues of associated toxicity, cost and resistance remain and there is
      a need for novel antiretroviral compounds to complement the existing therapy. We
      sought to develop a novel high-throughput method for identifying compounds that
      block later steps in the life cycle not targeted by current therapy. METHODS: We
      designed a high-throughput screen to identify inhibitors of post-integration
      steps in the HIV-1 life cycle. The screening method was applied to a library of
      compounds that included numerous FDA-approved small molecules. RESULTS: Among the
      small molecules that inhibited late stages in HIV-1 replication were members of
      the cardiac glycoside family. We demonstrate that cardiac glycosides potently
      inhibit HIV-1 gene expression, thereby reducing the production of infectious HIV
      1. We demonstrate that this inhibition is dependent upon the human Na(+)/K(+)
      ATPase, but independent of cardiac glycoside-induced increases in intracellular
      Ca(2+). CONCLUSIONS: We have validated a novel high-throughput screen to identify
      small molecule inhibitors of HIV-1 gene expression, virion assembly and budding.
      Using this screen, we have demonstrated that a number of FDA-approved compounds
      developed for other purposes potently inhibit HIV-1 replication, including the
      cardiac glycosides. Our work indicates that the entire cardiac glycoside family
      of drugs shows potential for antiretroviral drug development.

PMID- 24275121
TI  - The influence of lower-extremity function in elderly individuals' quality of life
      (QOL): an analysis of the correlation between SPPB and EQ-5D.
AB  - BACKGROUND: If an association between a decline in physical performance and
      subjective QOL is confirmed, the SPPB could be used as a predictor for declining
      QOL in older people. OBJECTIVE: This study aimed to elucidate the association
      between the short physical performance battery (SPPB) and QOL (EQ-5D) to
      determine the utility of the SPPB as a predictor of declining QOL. METHODS: The
      SPPB and the EQ-5D test were performed with a random sample of participants
      nested in the Korean Longitudinal Study of Aging (KLoSA) panel. Comparisons of
      the adjusted mean scores on the EQ-5D index between normal and abnormal SPPB
      groups were performed. We selected the quartiles of the EQ-5D index variables for
      the analysis. The association between the EQ-5D index and SPPB abnormality was
      examined using multinomial logistic regression analysis. Additionally, the
      associations between gait speed and chair stand time and the EQ-5D index were
      examined using the same analysis. RESULTS: Four hundred and twenty-two subjects
      were included in the analysis. The adjusted means for the EQ-5D index were
      significantly lower when the SPPB score was abnormal (p=0.022 for men, p=0.047
      for women). An abnormal SPPB score was significantly associated with the lowest
      quartile of EQ-5D index score (adjusted OR 3.54 in the lowest quartile for men;
      adjusted OR 2.50 and 3.37 in the lowest and second quartiles for women). Gait
      speed was significantly associated with the EQ-5D index for participants of both
      sexes, but standup time was associated with the EQ-5D index only for men.
      CONCLUSIONS: An abnormal SPPB score was associated with lower QOL. Thus, the SPPB
      has the potential to be used as an early predictor of declining QOL in clinical
      settings and epidemiological studies.

PMID- 24275120
TI  - Iron status in the elderly.
AB  - Iron deficiency anaemia is prevalent in older age, particularly after the age of
      80. Serum ferritin concentrations also decline, although there is no evidence to
      suggest that changes in iron stores are an inevitable consequence of ageing.
      Chronic inflammation is a common condition in older people, making the
      measurement of iron status difficult, and it is likely that elevated levels of
      circulating hepcidin are responsible for changes in iron metabolism that result
      in systemic iron depletion. Other contributory factors are poor diet and some
      medications, such as aspirin. Anaemia in older age has undesirable health
      outcomes, including increased susceptibility to falling and depression. However,
      there are concerns about possible adverse effects of iron supplements, either in
      relation to pro-inflammatory effects in the gut or inappropriate tissue iron
      deposition. Brain iron levels are increased with age-related degenerative
      diseases, but it is not known if this is the cause or a consequence of the
      disease, and genetic factors are likely to play a role. In order to maintain body
      iron within the normal range a personalised approach is required, taking into
      account all of the factors that may affect iron metabolism and the available
      strategies for preventing iron deficiency or overload. 

PMID- 24275122
TI  - Assessment of mental chronometry (MC) in healthy subjects.
AB  - OBJECTIVE: This study examined the temporal congruency between real and imagined
      movements and explored intermanual transfer effects in healthy subjects. METHODS:
      Seventy-six right-handed healthy subjects were allocated to three age groups and
      tested with a modified version of the Box and Block Test (BBT). We focussed on
      two aspects. First, the BBT was evaluated with respect to its ability to assess
      MC. Second, we were interested whether performance of motor imagery (MI) and real
      execution with one hand would modify performance with the other hand. To explore
      MC, we measured motor execution (ME) time as the time needed to perform the BBT,
      and MC time as the time difference between ME and the time needed for imagination
      of task execution. The BBT was performed with both hands consecutively to study
      transfer effects from one hand to the other and then repeated with the first hand
      for practice effects. RESULTS: The age group with the oldest subjects exhibited a
      slower BBT performance and a less precise MC than the other 2 age groups.
      Irrespective of the age, MC abilities could be transferred to the other hand,
      whereas ME only improved when repeating the task with the same hand. CONCLUSIONS:
      The BBT was able to demonstrate an age-related decline of dexterity and MC.
      Intermanual transfer of MI abilities occurred even after a single run.

PMID- 24275124
TI  - Active and non-active video gaming among Dutch adolescents: who plays and how
      much?
AB  - OBJECTIVES: The aim of study was to determine prevalence and identify demographic
      correlates of active and non-active gaming among adolescents. DESIGN: Cross
      sectional. METHODS: A survey, assessing game behavior and correlates, was
      conducted among adolescents (12-16 years, n = 373), recruited via schools.
      Multivariable logistic regression analyses were conducted to examine demographic
      correlates of active gaming (>= 1 h per week) and non-active gaming (>7h per
      week). RESULTS: Of all participants (n=373), 3% reported to play exclusively
      active games, 40% active games and non-active games, 40% exclusively non-active
      games, and 17% not playing video games at all. Active gaming adolescents played
      active games on average on 1.5 (sd = 1.2) days per school week for 36 (sd =
      32.9)min and 1 (sd = 0.54) day per weekend for 42 (sd = 36.5)min. Non-active
      gaming adolescents played on average on 3.3 (sd = 1.6) days per school week for
      65 (sd = 46.0)min and 1.4 (sd = 0.65) days per weekend for 80 (sd = 50.8)min.
      Adolescents attending lower levels of education were more likely to play active
      games >= 1 h per week than adolescents attending higher educational levels. Boys
      and older adolescents were more likely to play non-active games >7h per week,
      than girls or younger adolescents. CONCLUSIONS: Many adolescents play active
      games, especially those following a lower educational level, but time spent in
      this activity is relatively low compared to non-active gaming. To be feasible as
      a public health strategy, active gaming interventions should achieve more time is
      spent on active gaming at the expense of non-active gaming.

PMID- 24275123
TI  - Analysis of a lung defect in autophagy-deficient mouse strains.
AB  - Yeast Atg1 initiates autophagy in response to nutrient limitation. The Ulk gene
      family encompasses the mammalian orthologs of yeast ATG1. We created mice
      deficient for both Ulk1 and Ulk2 and found that the mice die within 24 h of
      birth. When found alive, pups exhibited signs of respiratory distress.
      Histological sections of lungs of the Ulk1/2 DKO pups showed reduced airspaces
      with thickened septae. A similar defect was seen in Atg5-deficient pups as both
      Ulk1/2 DKO and Atg5 KO lungs show numerous glycogen-laden alveolar type II cells
      by electron microscopy, PAS staining, and increased levels of glycogen in lung
      homogenates. No abnormalities were noted in expression of genes encoding
      surfactant proteins but the ability to incorporate exogenous choline into
      phosphatidylcholine, the major phospholipid component of surfactant, was
      increased in comparison to controls. Despite this, there was a trend for total
      phospholipid levels in lung tissue to be lower in Ulk1/2 DKO and Atg5 KO compared
      with controls. Autophagy was abundant in lung epithelial cells from wild-type
      mice, but lacking in Atg5 KO and Ulk1/2 DKO mice at P1. Analysis of the autophagy
      signaling pathway showed the existence of a negative feedback loop between the
      ULK1 and 2 and MTORC1 and 2, in lung tissue. In the absence of autophagy,
      alveolar epithelial cells are unable to mobilize internal glycogen stores
      independently of surfactant maturation. Together, the data suggested that
      autophagy plays a vital role in lung structural maturation in support of
      perinatal adaptation to air breathing. 

PMID- 24275125
TI  - Dignity in death: the triumph of politics over evidence.

PMID- 24275126
TI  - Reproducing our species and finding solutions.

PMID- 24275127
TI  - Should oncologists support the Affordable Care Act?

PMID- 24275128
TI  - Mistletoe: for cancer or just for Christmas?

PMID- 24275129
TI  - Time for evidence-based e-cigarette regulation.

PMID- 24275130
TI  - Perspectives on breast cancer in Arab populations.

PMID- 24275131
TI  - Adjuvant treatment for resected pancreatic adenocarcinoma-still an unresolved
      issue.

PMID- 24275132
TI  - CT screening for lung cancer: countdown to implementation.
AB  - Implementation of lung cancer CT screening is currently the subject of a major
      policy decision within the USA. Findings of the US National Lung Screening Trial
      showed a 20% reduction in lung cancer mortality and a 6.7% decrease in all-cause
      mortality; subsequently, five US professional and clinical organisations and the
      US Preventive Services Task Force recommended that screening should be
      implemented. Should national health services in Europe follow suit? The European
      community awaits mortality and cost-effectiveness data from the NELSON trial in
      2015-16 and pooled findings of European trials. In the intervening years, a
      recommendation is proposed that a demonstration trial is done in the UK. In this
      Review, we summarise the existing evidence and identify questions that remain to
      be answered before the implementation of international lung cancer screening
      programmes. 

PMID- 24275133
TI  - Ovarian transposition in prepubescent and adolescent girls with cancer.
AB  - Ovarian transposition was the first procedure proposed to preserve fertility in
      girls with cancer and is indicated for patients with tumours requiring pelvic
      radiation at doses of 42.0-58.4 Gy, much higher doses than those that can induce
      loss of ovarian function (4-20 Gy). Ovarian transposition is usually done after
      neoadjuvant chemotherapy and is completed by minimally invasive surgery or open
      surgery in case of concomitant resection of the abdominal tumour. According to
      the type of tumour, the ovaries are moved and placed in the paracolic gutters
      when the radiation field reaches the midline (for medulloblastoma or urogenital
      rhabdomyosarcoma), contralaterally to the tumour (for pelvic sarcomas), or in
      line with the iliac crests (for Hodgkin's lymphoma). However, in 10-14% of cases
      the procedure can fail to protect the ovaries. Although few long-term results in
      adults are available, normal hormonal function and pregnancies have been reported
      in a few long-term follow-up studies. In view of the continued development of
      fertility preservation techniques, ovarian transposition should be discussed at a
      multidisciplinary meeting at the time of cancer diagnosis. 

PMID- 24275134
TI  - Neonatal cancer.
AB  - Neonatal cancer is rare and comprises a heterogeneous group of neoplasms with
      substantial histological diversity. Almost all types of paediatric cancer can
      occur in fetuses and neonates; however, the presentation and behaviour of
      neonatal tumours often differs from that in older children, leading to
      differences in diagnosis and management. The causes of neonatal cancer are
      unclear, but genetic factors probably have a key role. Other congenital
      abnormalities are frequently present. Teratoma and neuroblastoma are the most
      common histological types of neonatal cancer, with soft-tissue sarcoma,
      leukaemia, renal tumours, and brain tumours also among the more frequent types.
      Prenatal detection, most often on routine ultrasound or in the context of a known
      predisposition syndrome, is becoming more common. Treatment options pose
      challenges because of the particular vulnerability of the population. Neonatal
      cancer raises diagnostic, therapeutic, and ethical issues, and management
      requires a multidisciplinary approach. 

PMID- 24275135
TI  - Recommendations for breast cancer surveillance for female survivors of childhood,
      adolescent, and young adult cancer given chest radiation: a report from the
      International Late Effects of Childhood Cancer Guideline Harmonization Group.
AB  - Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were
      given radiation to fields that include breast tissue (ie, chest radiation) have
      an increased risk of breast cancer. Clinical practice guidelines are essential to
      ensure that these individuals receive optimum care and to reduce the detrimental
      consequences of cancer treatment; however, surveillance recommendations vary
      among the existing long-term follow-up guidelines. We applied evidence-based
      methods to develop international, harmonised recommendations for breast cancer
      surveillance among female survivors of CAYA cancer who were given chest radiation
      before age 30 years. The recommendations were formulated by an international,
      multidisciplinary panel and are graded according to the strength of the
      underlying evidence. 

PMID- 24275136
TI  - Synthetic embryonic lethality upon deletion of the ER cochaperone p58(IPK) and
      the ER stress sensor ATF6alpha.
AB  - The unfolded protein response (UPR) is activated as a consequence of alterations
      to ER homeostasis. It upregulates a group of ER chaperones and cochaperones, as
      well as other genes that improve protein processing within the secretory pathway.
      The UPR effector ATF6alpha augments-but is not essential for-maximal induction of
      ER chaperones during stress, yet its role, if any, in protecting cellular
      function during normal development and physiology is unknown. A systematic
      analysis of multiple tissues from Atf6alpha-/- mice revealed that all tissues
      examined were grossly insensitive to loss of ATF6alpha. However, combined
      deletion of ATF6alpha and the ER cochaperone p58(IPK) resulted in synthetic
      embryonic lethality. These findings reveal for the first time that an intact UPR
      can compensate for the genetic impairment of protein folding in the ER in vivo.
      The also expose a role for p58(IPK) in normal embryonic development. 

PMID- 24275137
TI  - Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to
      chemoradiotherapy in vitro.
AB  - 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely
      used for colorectal cancer treatment, but colorectal cancer cells are often
      resistant to primary or acquired 5-FU therapy. Several studies have shown that
      miR-21 is significantly elevated in colorectal cancer. This suggests that this
      miRNA might play a role in this resistance. In this study, we investigated this
      possibility and the possible mechanism underlying this role. We showed that
      forced expression of miR-21 significantly inhibited apoptosis, enhanced cell
      proliferation, invasion, and colony formation ability, promoted G1/S cell cycle
      transition and increased the resistance of tumor cells to 5-FU and X radiation in
      HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects
      on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy.
      Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and
      indirectly regulated the expression of thymidine phosphorylase (TP) and
      dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may
      play an important role in the 5-FU resistance of colon cancer cells. 

PMID- 24275138
TI  - Hypoxia and hypoxia mimetic cooperate to counteract tumor cell resistance to
      glucose starvation preferentially in tumor cells with mutant p53.
AB  - We demonstrated that exogenous pyruvate promotes survival under glucose depletion
      in aerobic mutant p53 (R175H) human melanoma cells. Others subsequently indicated
      that mutant p53 tumor cells undergo p53 degradation and cell death under aerobic
      glucose-free conditions. Since glucose starvation occurs in hypoxic gradients of
      poorly vascularized tumors, we investigated the role of p53 siRNA under hypoxia
      in wt p53 C8161 melanoma using glucose starvation or 5mM physiological glucose.
      p53 Silencing decreased survival of glucose-starved C8161 melanoma with pyruvate
      supplementation under hypoxia (<=1% oxygen), but increased resistance to
      glycolytic inhibitors oxamate and 2-deoxyglucose in 5mM glucose, preferentially
      under normoxia. Aiming to counteract hypoxic tumor cell survival irrespective of
      p53 status, genetically-matched human C8161 melanoma harboring wt p53 or mutant
      p53 (R175H) were used combining true hypoxia (<=1% oxygen) and hypoxia mimetic
      CoCl2. No significant decrease in metabolic activity was evidenced in C8161
      melanoma irrespective of p53 status in 2.5mM glucose after 48h of physical
      hypoxia. However, combining the latter with 100MUM CoCl2 was preferentially toxic
      for mutant p53 C8161 melanoma, and was enhanced by catalase in wt p53 C8161
      cells. Downregulation of MnSOD and LDHA accompanied the toxicity induced by
      hypoxia and CoCl2 in 5mM glucose, and these changes were enhanced by oxamate or 2
      deoxyglucose. Our results show for the first time that survival of malignant
      cells in a hypoxic microenvironment can be counteracted by hypoxia mimetic co
      treatment in a p53 dependent manner.

PMID- 24275140
TI  - Effects of oxysterols on the blood-brain barrier: implications for Alzheimer's
      disease.
AB  - Altered brain cholesterol homeostasis plays a key role in neurodegenerative
      diseases such as Alzheimer's disease (AD). For a long time, the blood-brain
      barrier (BBB) was basically considered as a barrier isolating the brain from
      circulating cholesterol, however, several lines of evidence now suggest that the
      BBB strictly regulates the exchanges of sterol between the brain and the
      peripheral circulation. Oxysterols, synthesized by neurons or by peripheral
      cells, cross the BBB easily and modulate the expression of several enzymes,
      receptors and transporters which are involved not only in cholesterol metabolism
      but also in other brain functions. This review article deals with the way
      oxysterols impact BBB cells. These perspectives open new routes for designing
      certain therapeutical approaches that target the BBB so that the onset and/or
      progression of brain diseases such as AD may be modulated. 

PMID- 24275139
TI  - CB2 cannabinoid receptor is a novel target for third-generation selective
      estrogen receptor modulators bazedoxifene and lasofoxifene.
AB  - The purpose of the current study was to investigate the ability of the third
      generation selective estrogen receptor modulators (SERMs) bazedoxifene and
      lasofoxifene to bind and act on CB2 cannabinoid receptor. We have identified, for
      the first time, that CB2 is a novel target for bazedoxifene and lasofoxifene. Our
      results showed that bazedoxifene and lasofoxifene were able to compete for
      specific [(3)H]CP-55,940 binding to CB2 in a concentration-dependent manner. Our
      data also demonstrated that by acting on CB2, bazedoxifene and lasofoxifene
      concentration-dependently enhanced forskolin-stimulated cAMP accumulation.
      Furthermore, bazedoxifene and lasofoxifene caused parallel, rightward shifts of
      the CP-55,940, HU-210, and WIN55,212-2 concentration-response curves without
      altering the efficacy of these cannabinoid agonists on CB2, which indicates that
      bazedoxifene- and lasofoxifene-induced CB2 antagonism is most likely competitive
      in nature. Our discovery that CB2 is a novel target for bazedoxifene and
      lasofoxifene suggests that these third-generation SERMs can potentially be
      repurposed for novel therapeutic indications for which CB2 is a target. In
      addition, identifying bazedoxifene and lasofoxifene as CB2 inverse agonists also
      provides important novel mechanisms of actions to explain the known therapeutic
      effects of these SERMs. 

PMID- 24275141
TI  - Overexpression of tomato SpMPK3 gene in Arabidopsis enhances the osmotic
      tolerance.
AB  - Mitogen-activated protein kinase (MAPK) class plays diverse roles in plant
      response to abiotic stresses. SpMPK3, a serine/threonine protein kinase
      containing a Thr-Glu-Tyr (TEY) activation domain, has been reported to function
      against bacterial, fungus and insect attack in tomatoes. But, its roles in
      abiotic stress response are poorly experienced. Herein, the experiment we have
      conducted demonstrates that there is a substantial increase of SpMPK3 expression
      in tomato leaves by drought, salt and cold stress. Transgenic Arabidopsis plants
      overexpressing SpMPK3 showed improved seed germination and antioxidant capacity
      under osmotic stress, but decreased seed germination with ABA treatment compared
      to wile-type. In addition, SpMPK3 overexpression enhanced the transcription
      levels of ABA inducible genes-RD29A, RAB18 and RD22, and transcription factor
      genes-ZAT6, ZAT10 and MYB44, in transgenic Arabidopsis compared with wild-type in
      response to ABA or salt stress. These results suggest that SpMPK3 is a positive
      regulator in response to osmotic stress in Arabidopsis at germination and
      development stage. 

PMID- 24275142
TI  - "Drinking in the dark" (DID) procedures: a model of binge-like ethanol drinking
      in non-dependent mice.
AB  - This review provides an overview of an animal model of binge-like ethanol
      drinking that has come to be called "drinking in the dark" (DID), a procedure
      that promotes high levels of ethanol drinking and pharmacologically relevant
      blood ethanol concentrations (BECs) in ethanol-preferring strains of mice.
      Originally described by Rhodes, Best, Belknap, Finn, and Crabbe (2005), the most
      common variation of the DID procedure, using singly housed mice, involves
      replacing the water bottle with a bottle containing 20% ethanol for 2-4 h,
      beginning 3 h into the dark cycle. Using this procedure, high ethanol drinking
      strains of mice (e.g., C57BL/6J) typically consume enough ethanol to achieve BECs
      greater than 100 mg/dL and to exhibit behavioral evidence of intoxication. This
      limited access procedure takes advantage of the time in the animal's dark cycle
      in which the levels of ingestive behaviors are high, yet high ethanol intake does
      not appear to stem from caloric need. Mice have the choice of drinking or
      avoiding the ethanol solution, eliminating the stressful conditions that are
      inherent in other models of binge-like ethanol exposure in which ethanol is
      administered by the experimenter, and in some cases, potentially painful. The DID
      procedure is a high throughput approach that does not require extensive training
      or the inclusion of sweet compounds to motivate high levels of ethanol intake.
      The high throughput nature of the DID procedure makes it useful for rapid
      screening of pharmacological targets that are protective against binge-like
      drinking and for identifying strains of mice that exhibit binge-like drinking
      behavior. Additionally, the simplicity of DID procedures allows for easy
      integration into other paradigms, such as prenatal ethanol exposure and
      adolescent ethanol drinking. It is suggested that the DID model is a useful tool
      for studying the neurobiology and genetics underlying binge-like ethanol
      drinking, and may be useful for studying the transition to ethanol dependence. 

PMID- 24275143
TI  - A novel hairpin-like antimicrobial peptide from barnyard grass (Echinochloa
      crusgalli L.) seeds: Structure-functional and molecular-genetics
      characterization.
AB  - A novel plant hairpin-like defense polypeptide named EcAMP3 was isolated from
      latent barnyard grass (Echinochloa crusgalli L.) seeds. The native peptide and
      its recombinant analogue were characterized. EcAMP3 displays antifungal and
      antibacterial activity in vitro. The gene family encoding EcAMPs precursor
      protein was also characterized; the genes and pseudogenes of this family show 97
      100% homology. Every member of EcAMPs precursor family contains seven identical
      cysteine motifs: C1XXXC2(11-13)C3XXXC4. One of those motifs corresponds to the
      isolated peptide. EcAMP3 is the first member of the plant hairpin-like peptide
      family that inhibits the growth of phytopathogenic bacteria. Obtained results can
      explain the nature of the complex resistance of barnyard grass to a variety of
      pathogenic microorganisms. 

PMID- 24275144
TI  - Controversial identification in a historical case is illustrative of the
      complexity of DNA typing in forensic research. Response to Charlier et al.
AB  - The previously published genetic identification of presumptive samples attributed
      to two French kings, Henri IV and Louis XVI, by Charlier et al., was recently
      refuted by a genetic genealogic approach. This (provisional) refutation
      illustrates the difficulties in confirming the identification of historical DNA
      samples using limited genetic data. Therefore, we want to stress the necessity of
      including the genetic genealogic approach--which relies on DNA typing of living
      relatives of the presumptive donor as a confirmed reference--to validate genetic
      results in historical cases. Moreover, the popularity and broad media coverage of
      such studies are useful in bringing awareness to the general public, non-DNA
      forensic experts and lawyers about the complexity of DNA typing in forensic
      cases.

PMID- 24275145
TI  - Chronic rhinitis and its association with headache frequency and disability in
      persons with migraine: results of the American Migraine Prevalence and Prevention
      (AMPP) Study.
AB  - BACKGROUND: Rhinitis is a comorbidity of migraine, but its relationship to
      migraine headache frequency and headache-related disability is unknown.
      OBJECTIVES: To determine if rhinitis and its subtypes are associated with an
      increased frequency and associated disability of migraine. METHODS: The AMPP
      Study is a longitudinal study of individuals with "severe" headache from the US
      population. Respondents meeting ICHD-2 criteria for migraine in 2008 were
      identified and the presence of rhinitis was determined using the European
      Community Respiratory Health Survey (ECRHS). Those with rhinitis were subtyped as
      allergic, non-allergic, mixed and unclassified based on a rhinitis questionnaire.
      The primary outcome measures were categories of headache-day frequency and
      headache-related disability as measured by the Migraine Disability Assessment
      Scale (MIDAS). Logistic regression for ordered categories was used for modeling
      each outcome separately, adjusted for sociodemographics profile, headache
      features, headache treatments and comorbidities. RESULTS: The AMPP Study
      questionnaire was mailed to 17,892 persons and returned by 60.1% of respondents.
      Among the migraine sample ( N  = 5849), 66.8% had rhinitis with mixed rhinitis as
      the most common form. The presence of rhinitis of any type was associated with
      headache frequency after adjusting for sociodemographic variables only (OR 1.33;
      95% CI 1.16, 1.53) and in the fully adjusted model (OR 1.25; 95% CI 1.05-1.49).
      Headache-related disability (MIDAS category) was associated with rhinitis after
      adjusting for sociodemographic features (OR 1.30; 95% CI 1.17-1.46), but lost
      significance in the fully adjusted model (OR 1.10; 95% CI 0.96-1.26). Mixed
      rhinitis was associated with an increased headache frequency category in the
      model adjusted for sociodemographics (OR 1.45; 95% CI 1.24-1.70) and in that
      adjusted for all covariates (OR 1.28; 95% CI 1.05-1.57). The odds ratio for MIDAS
      categories were similarly increased in both models for the mixed rhinitis group.
      CONCLUSIONS: The frequency and disability of migraine are higher in persons with
      rhinitis, particularly those with mixed rhinitis. These results, however, should
      be considered preliminary until confirmed in future studies because of the modest
      questionnaire response rate in this study.

PMID- 24275146
TI  - Trends in long-term oxygen therapy for COPD in Denmark from 2001 to 2010.
AB  - OBJECTIVES: To evaluate changes in demographics, incidence, prevalence, treatment
      modalities, and survival of COPD patients on long-term oxygen therapy (LTOT) from
      year 2001-2010 in Denmark. METHODS: All 14,965 COPD patients with COPD treated
      LTOT in Denmark in the period 2001-2010. RESULTS: During the study period, the
      incidence and prevalence of COPD patients on LTOT increased from 30.5 to 32.2 per
      100.000, and from 42.0 to 48.1 per 100.000, respectively. Mean age of patients
      increased from 73.4 to 74.8 years, P < 0.001. An increasing number of patients
      were prescribed LTOT in connection with discharge after hospitalisation for an
      exacerbation (2001 vs. 2010: 76.5% vs. 91.7%, P < 0.001); were prescribed oxygen
      15-24 h/day (85.8% vs. 89.5%, P < 0.001); had mobile oxygen (56.4% vs. 94.2%, P <
      0.001), and stopped LTOT alive within 6 months (20.6% vs. 30.8%, P < 0.001).
      Ninety-nine percent of the patients received oxygen concentrator or liquid oxygen
      with no change in the study period (P = 0.66). The median survival on LTOT
      increased insignificantly from 16.5 to 17.8 months (P = 0.12). Women had a lower
      risk of dying compared with men, with an adjusted hazard ratio of 0.81 (95%
      confidence interval (CI) 0.78-0.84), P < 0.001). During the study period, the
      risk of death for women, compared to men, decreased significantly with a hazard
      ratio of 0.978 (95% CI: 0.964-0.992) per calendar year. CONCLUSIONS: The
      incidence of COPD patients on LTOT in Denmark has levelled of during recent
      years, and the quality of prescribing LTOT and follow up has improved. Women had
      better survival than men, and this difference has increased during the study
      period.

PMID- 24275147
TI  - SC-60, a dimer-based sorafenib derivative, shows a better anti-hepatocellular
      carcinoma effect than sorafenib in a preclinical hepatocellular carcinoma model.
AB  - Sorafenib is the first approved targeted therapeutic reagent for hepatocellular
      carcinoma. Here, we report that SC-60, a dimer-based sorafenib derivative,
      overcomes the resistance of sorafenib and shows a better anti-hepatocellular
      carcinoma effect in vitro and in vivo. SC-60 substantially increased SH2 domain
      containing phosphatase 1 (SHP-1) phosphatase activity in hepatocellular carcinoma
      cells and purified SHP-1 proteins, suggesting that SC-60 affects SHP-1 directly.
      Molecular docking and truncated mutants of SHP-1 further confirmed that SC-60
      interferes with the inhibitory N-SH2 domain to relieve the closed catalytic
      protein tyrosine phosphatase domain of SHP-1. Deletion of N-SH2 domain (dN1) or
      point mutation (D61A) of SHP-1 abolished the effect of SC-60 on SHP-1, p-STAT3,
      and apoptosis. Importantly, SC-60 exhibited significant survival benefits
      compared with sorafenib in a hepatocellular carcinoma orthotopic model via
      targeting the SHP-1/STAT3-related signaling pathway. In summary, dimer derivative
      of sorafenib, SC-60, is a SHP-1 agonist and may be a potent reagent for
      hepatocellular carcinoma-targeted therapy.

PMID- 24275148
TI  - Phytotoxicity effects and biological responses of Arabidopsis thaliana to 2,3,7,8
      tetrachlorinated dibenzo-p-dioxin exposure.
AB  - Dioxins are persistent organic pollutants. Their bioaccumulation in the food
      chain makes dioxins a considerable risk for human health. The use of plants for
      removing toxic organic compounds, including dioxins, is a safe and efficient
      strategy. Herein we studied the toxicity effects and the biological responses in
      Arabidopsis thaliana to 2',3',7',8'-tetrachlorinated dibenzo-p-dioxin (TCDD)
      exposure. First, TCDD-induced toxicity was demonstrated using several parameters
      including, a decrease in seed germination, a loss in fresh weight with a striking
      decrease in chlorophyll content, but not in carotenoids, and an augmentation in
      the biomass of the lateral roots system, but not in the elongation of the primary
      root. Uptake of TCDD by Arabidopsis was confirmed. Responses to TCDD-exposure
      were marked by an enhanced level of hydrogen peroxide H2O2 production and a
      massive stimulation of anti-oxidative enzyme activities. Moreover, a significant
      variation in the transcript level of transcription factor genes, bHLH, MYB and
      AP2-EREBP was detected in Arabidopsis shoot and an up-regulation of WRKY, MYB and
      IAA was observed in the root. Our results illustrate the TCDD-induced toxicity
      effects and the biological responses of Arabidopsis to TCDD. Better understanding
      of the plants ability to detoxifydioxins would help to improve their use as a
      safe bioremediators. 

PMID- 24275149
TI  - New insight into pesticide partition coefficient Kd for modelling pesticide
      fluvial transport: application to an agricultural catchment in south-western
      France.
AB  - Pesticides applied on crops are leached with rainfall to groundwater and surface
      water. They threat the aquatic environment and may render water unfit for human
      consumption. Pesticide partitioning is one of the pesticide fate processes in the
      environment that should be properly formalised in pesticide fate models. Based on
      the analysis of 7 pesticide molecules (alachlor, atrazine, atrazine's
      transformation product deethylatrazine or DEA, isoproturon, tebuconazole and
      trifluralin) sampled from July 2009 to October 2010 at the outlet of the river
      Save (south-western France), the objectives of this study were (1) to check which
      of the environmental factors (discharge, pH, concentrations of total suspended
      matter (TSM), dissolved organic carbon (DOC) and particulate organic carbon (POC)
      could control the pesticide sorption dynamic, and (2) to establish a relationship
      between environmental factors, the partition coefficient Kd and the octanol/water
      distribution coefficient Kow. The comparison of physico-chemical parameters
      values during low flow and high flow shows that discharge, TSM and POC are the
      factors most likely controlling the pesticide sorption processes in the Save
      river network, especially for lower values of TSM (below 13mgL(-1)). We therefore
      express Kd depending on the widely literature-related variable Kow and on the
      commonly simulated variable TSM concentration. The equation can be implemented in
      any model describing the fluvial transport and fate of pesticides in both
      dissolved and sorbed phases, thus, Kd becomes a variable in time and space. The
      Kd calculation method can be applied to a wide range of catchments and organic
      contaminants. 

PMID- 24275150
TI  - Enhancement of toxic effects of phenanthrene to Daphnia magna due to the presence
      of suspended sediment.
AB  - In the present work, the influences of suspended sediment (SPS) on the toxic
      effects of phenanthrene (PHE), one kind of polycyclic aromatic hydrocarbons, to
      Daphnia magna was studied using a dialysis bag simulation system, which equalized
      the freely dissolved concentration of PHE between outside the dialysis bag in the
      presence of SPS and inside the dialysis bag in the absence of SPS. The
      immobilization and total superoxide dismutase (T-SOD) activity of Daphnia magna
      caused by PHE (0-0.8 mg L(-1)) were investigated under the influence of different
      SPS concentrations (0, 1, 3, 5 g L(-1)) during a 96 h-exposure. The results
      showed that, compared to the absence of SPS, the presence of SPS (1-5 g L(-1))
      increased the immobilization of Daphnia magna by 1.6-2.7 times when the freely
      dissolved concentration of PHE was identical in both systems. The inhibition of T
      SOD activity of Daphnia magna by PHE was significantly greater in the presence of
      SPS than in the absence of SPS (p<0.01). This infers that the PHE sorbed on SPS
      might be bioavailable and enhanced the toxic effect of PHE to Daphnia magna. The
      bioavailable fraction of PHE sorbed on SPS ranged from 10.1% to 22.7%, and the
      contribution of PHE sorbed on SPS to the immobilization caused by total PHE in
      the exposure system increased with SPS concentration, with the contribution ratio
      increasing from 36.7% to 57.7% when SPS concentration increased from 1 to 5 g L(
      1). This study suggests that only considering the concentrations of hydrophobic
      organic compounds in the water phase may underestimate their toxicity; and the
      hydrophobic organic compounds sorbed on SPS should not be ignored in assessment
      of water quality and the establishment of water quality standard in the future.

PMID- 24275151
TI  - Larvicidal activity of Mentha x villosa Hudson essential oil, rotundifolone and
      derivatives.
AB  - The aim of this study was to evaluate the larvicidal activity of Mentha x villosa
      essential oil (MVEO) and its major constituent, rotundifolone, against larvae of
      Aedes aegypti. Additionally, a set of 15 analogues of the rotundifolone were
      evaluated to identify the molecular characteristics which contribute to the
      larvicidal effect. The results from the present study showed that the MVEO
      exhibited outstanding toxic effects against Ae. aegypti larvae (LC50=45.0ppm).
      Rotundifolone exhibited reasonable larvicidal activity (LC50=62.5ppm). With
      respect to comparative study of rotundifolone and its analogues, all tested
      compounds were less potent than rotundifolone, except (-)-limonene. In general,
      replacement of C-C double bonds by epoxides groups decreases the larvicidal
      potency. The presence of alpha,beta-unsaturated carbonyls contributes to the
      larvicidal toxicity. The addition of hydroxyl groups in the chemical structure
      resulted in less potent compounds. Furthermore, the enantioselectivity seems to
      play an important role for the larvicidal toxicity.

PMID- 24275152
TI  - Assessment of chromium-contaminated groundwater using a thiosulfate-oxidizing
      bacteria (TOB) biosensor.
AB  - The effect of Cr(6+)-contaminated groundwater was assessed using thiosulfate
      oxidizing bacteria (TOB). Electrical conductivity (EC), pH, and sulfate
      production were determined based on thiosulfate oxidation. Final pH values in the
      different test treatments of Cr(6+)-contaminated groundwater (50-1000 MUg
      Cr(6+)L(-1)) ranged from 2.02 +/- 0.09 to 7.76 +/- 0.07 and EC ranged from 5.95
      +/- 0.03 to 3.63 +/- 0.03 mS cm(-1). Inhibition of TOB due to Cr(6+) was between
      16.7% and 100%, with higher levels of inhibition occurring at higher Cr(6+)
      concentrations. The median effective concentration (EC50) was 78.96 MUg Cr(6+)L(
      1). These data demonstrate that TOB can detect less than 100 MUg L(-1) of Cr(6+)
      in the groundwater and can be used as an effective bioassay for toxicity
      assessment.

PMID- 24275153
TI  - Catalytic reforming of toluene as tar model compound: effect of Ce and Ce-Mg
      promoter using Ni/olivine catalyst.
AB  - Tar produced by biomass gasification as a route of renewable energy must be
      removed before the gas can be used. This study was undertaken using toluene as a
      model tar compound for evaluating its steam reforming conversion with three Ni
      based catalysts, Ni/olivine, Ni-Ce/olivine and Ni-Ce-Mg/olivine. Effects of Ce
      and Mg promoters on the reaction activity and coke deposition were studied.
      Overall the performance of Ce and Mg promoted Ni/olivine catalysts is better than
      that of only Ce promoter and Ni/olivine alone. The experimental results indicate
      that Ni-Ce-Mg/olivine catalysts could improve the resistance to carbon
      deposition, enhance energy gases yield and resist 10ppm H2S poison at 100mLmin(
      1) for up to 400min. Furthermore, the activity of catalysts was related to the
      steam/carbon (S/C) ratios; at S/C ratio=5, T=790 degrees C, space velocity=782h(
      1) and t=2h, the Ni-Ce-Mg/olivine system yielded 89% toluene conversion, 5.6Lh(
      1) product gas rate, 62.6mol% H2 content and 10% (mol useful gas mol(-1) toluene)
      energy yield. Moreover, at low S/C ratio, it had higher reaction activity and
      better ability to prevent coking. There is a small amount of carbon deposition in
      the form of amorphous carbon after 7h. Various characterization techniques such
      as XRD, FTIR and thermogravimetric were performed to investigate the coke
      deposition of Ni/olivine, Ni-Ce/olivine and Ni-Ce-Mg/olivine. It is suggested
      that 3% Ni-1% Ce-1% Mg/olivine was the most promising catalyst due to its minimum
      coke amount and the lower activation energy of coke burning. 

PMID- 24275154
TI  - Acquired von Willebrand syndrome in patients with Gaucher disease.
AB  - Although various coagulation abnormalities occur in patients with Gaucher disease
      (GD), von Willebrand factor (vWF) deficiency has rarely been reported. A
      retrospective review of six treatment naive cases with GD and concomitant vWF
      deficiency over a 12-year-period in a single center is presented. All patients
      had a personal history of prior hemorrhages. Based on both reduced level of vWF
      antigen (vWF:Ag, range 14-56%) and ristocetin cofactor activity (vWF:RCo, range
      12-53%), with a vWF:RCo/Ag ratio >0.7, the diagnosis of type 1 von Willebrand
      disease was made in all six cases. During enzyme replacement therapy (ERT) of a 2
      year duration all patients normalized their vWF:Ag levels. Based on the positive
      ERT effect on vWF:Ag levels, vWF deficiency was assumed to be acquired. It should
      be noted that beside vWF deficiency four patients with GD exhibited mild
      thrombocytopenia (range 81-131*10(9)/L) and three had additional hemostatic
      defects (reduced collagen platelet aggregation, FV, FXI and FXII deficiencies). 

PMID- 24275155
TI  - Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with
      cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian
      cancer: preliminary clinical experience.
AB  - OBJECTIVE: To assess the activity of laparoscopic Pressurized IntraPeritoneal
      Aerosol Chemotherapy (PIPAC) in women with recurrent, platinum-resistant ovarian
      cancer. METHODS: Prospective case series using repeated courses q 28-42 days of
      PIPAC containing cisplatin 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2) at 12 mmHg and
      37 degrees C for 30 min. Objective tumor response was defined as tumor regression
      on histology and peritoneal carcinomatosis index (PCI) improvement on repeated
      video-laparoscopy. RESULTS: 34 PIPAC procedures were performed in 18 women, in 8
      instances combined with cytoreductive surgery (CRS). Eight women had repeated
      PIPAC and objective tumor response was observed in 6 (complete remission: 1;
      partial remission: 2; stable disease: 3). Five adverse events WHO grade >= 2 were
      noted, 3 of them after combined CRS. No perioperative mortality occurred. Median
      follow-up was 192 days (min. 13-max. 639). Cumulative survival after 400 days was
      62% and mean actuarial survival time was 442 days. In a multivariable regression
      analysis with objective tumor response (yes vs. no) as the dependent variable and
      PIPAC (1 vs.>1), patient age (<75 vs.>=75 years), serum CA-125 (<1000 vs.>1000
      U/mL), and the presence of ascites (yes vs. no) as independent variables, PIPAC
      independently predicted objective tumor response. CONCLUSION: PIPAC has activity
      in women with recurrent, platinum-resistant ovarian cancer and should be
      investigated in prospective clinical trials.

PMID- 24275156
TI  - A model for ballistic transport across locally gated graphene bipolar junctions.
AB  - An alternative model of Gaussian-type potential is suggested, which allows us to
      describe the transport properties of the locally gated graphene bipolar junctions
      in all possible charge density regimes, including a smooth transition between the
      regimes. Using this model we systematically study the transmission probability,
      the resistances, the current-voltage characteristics, and the shot noise for
      ballistic graphene bipolar junctions of different top gate lengths under largely
      varying gate voltages. Obtained results on the one hand show multifarious
      manifestations of the Klein tunneling and the interference effects, and on the
      other hand describe well typical experimental data on the junction resistances. 

PMID- 24275157
TI  - Short-term glucosamine infusion increases islet blood flow in anesthetized rats.
AB  - Impaired glucose tolerance and type 2 diabetes in rodents are associated with
      increased islet blood flow. If this is important for modulation of the endocrine
      function is at present unknown. We evaluated if glucosamine infusion, which
      induces peripheral insulin resistance and glucose intolerance, could be used to
      acutely increase islet blood flow. We infused anaesthetized Sprague-Dawley rats
      for 2 h with glucosamine (6 mg/kg body weight), in some cases followed by glucose
      administration. The former induced a 2-fold increase in serum insulin
      concentrations while plasma glucose remained unchanged. In vitro an augmented
      insulin response to hyperglycemia and decreased insulin content in batch type
      islet incubations with glucosamine for 24 h were seen. After 2 h glucosamine
      exposure in vitro, insulin release was decreased. In vivo glucosamine infusion
      increased islet blood flow, without affecting other regional blood flow values.
      Glucose increased islet blood flow to the same extent in control and glucosamine
      infused rats. When exposed to 10 mmol/L glucosamine arterioles of isolated
      perfused islets showed a 10% dilation of their vascular smooth muscle. Thus,
      application of this model leads to acute hyperinsulinemia in vivo but a decreased
      insulin release in vitro, which suggests that effects not located to beta cells
      are responsible for the effects seen in vivo. An increased islet blood flow in
      previously healthy animals was also seen after glucose administration, which can
      be used to further dissect the importance of blood flow changes in islet
      function. 

PMID- 24275158
TI  - Multilevel socioeconomic status and incidence of frailty post myocardial
      infarction.
AB  - BACKGROUND: Frailty predicts mortality and hospitalizations in post-myocardial
      infarction (MI) patients. Socioeconomic status (SES) demonstrates a clear
      relationship with post-MI outcomes and is also associated with community frailty;
      however this relationship has yet to be evaluated in post-MI patients. We
      investigated the predictive value of socioeconomic factors in the development of
      post-MI frailty. METHODS: A cohort of 1151 post-MI patients was followed up from
      initial hospitalization in 1992-1993 for 10-13 years. Individual and neighborhood
      SES measures were assessed at baseline and frailty was assessed during follow-up
      via an index of deficit accumulation. Logistic regression models and
      discrimination indices enabled determination of the predictive value of
      socioeconomic factors over basic clinical variables in classifying frailty risk.
      RESULTS: During follow-up, 399 patients (35%) developed frailty. Individual and
      neighborhood SES were significantly and independently associated with the risk of
      developing frailty. Low income patients had more than twice the risk of becoming
      frail compared with those with high income [odds ratio (OR), 2.29, 95% CI 1.41
      3.73]; while being in the lower vs. upper neighborhood SES tertile was associated
      with a 60% increased odds (OR, 1.60, 95% CI 1.03-2.49). Inclusion of multilevel
      SES yielded substantial gains in c-statistic (0.70 to 0.76), net reclassification
      improvement (21.4%) and integrated discrimination improvement (6.4%) over basic
      clinical factors (all p<0.001), indicating increased predictive value and gains
      in sensitivity and specificity. CONCLUSIONS: Individual and neighborhood
      socioeconomic factors influence the development of frailty post-MI, and
      contribute to risk discrimination in this population.

PMID- 24275160
TI  - What is responsible for a large and unusual outbreak of leishmaniasis in Madrid?
AB  - Several towns in the southwest of Madrid, Spain, have been suffering from an
      outbreak of leishmaniasis since 2009 and, by December 2012, human infections had
      increased significantly. Although dogs are the main reservoir host, hares are
      suspected as a potential culprit for the surprising increase of cases. 

PMID- 24275161
TI  - Coronary artery embolism causing acute myocardial infarction in patients with
      mechanical heart valve prosthesis: which is the optimal treatment?
AB  - OBJECTIVE: Coronary artery embolism resulting in acute myocardial infarction
      (AMI) is an infrequent but potentially life-threatening occurrence. To date,
      there is still no consensus in the literature regarding the optimal therapeutic
      algorithm for embolic myocardial infarction. PATIENTS: We present our experience
      with three patients who had mechanical valve prosthesis and suffered from AMI due
      to coronary artery embolism in the setting of sub-therapeutic or interrupted anti
      coagulation therapy. Those patients were treated with intracoronary thrombolysis,
      thrombus aspiration followed by balloon angioplasty and thrombus aspiration
      alone, respectively. RESULTS: In our case 1, the coronary angiogram demonstrated
      extensive thrombus within the left circumflex coronary artery and extending into
      the left anterior descending (LAD). We performed intracoronary thrombolytic
      therapy, which results in completed thrombus resolution and favourable clinical
      outcome. In our case 3, coronary angiography revealed massive thrombus within the
      middle-LAD with a TIMI grade 3 distal flow. The patient underwent a successful
      thrombus aspiration procedure without stent implantation. In our case 2, the
      coronary angiography revealed total occlusion of the middle LAD, and thrombus
      aspiration was initially performed because of the large thrombus burden. However,
      this approach was unsuccessful and so the patient was then treated with balloon
      angioplasty, resulting in TIMI 2 flow. CONCLUSION: Embolic myocardial infarction,
      although uncommon, can occur in predisposed groups such as those with prosthetic
      mechanical valves with sub-therapeutic anticoagulation. The treatment for this
      specific group of patients needs to be tailored individually.

PMID- 24275163
TI  - Quercetin exerts anti-melanoma activities and inhibits STAT3 signaling.
AB  - Melanoma is highly resistant to chemotherapy, and the mortality rate is
      increasing rapidly worldwide. STAT3 signaling has been implicated in the
      pathogenesis of melanoma and constitutive activated STAT3 has been validated can
      as a target for melanoma therapy. Quercetin, a noncarcinogenic dietary flavonoid
      with low toxicity, has been shown to exert anti-melanoma activity. However, the
      anti-melanoma mechanisms of quercetin are not fully understood. In this study, we
      sought to test the involvement of STAT3 signaling in the inhibitory effects of
      quercetin on melanoma cell growth, migration and invasion. Our results showed
      that exposure to quercetin resulted in inhibition of proliferation of melanoma
      cells, induction of cell apoptosis, and suppression of migratory and invasive
      properties. Mechanistic study indicated that quercetin inhibited the activation
      of STAT3 signaling by interfering with STAT3 phosphorylation, and reducing STAT3
      nuclear localization. This inhibited STAT3 transcription activity and down
      regulated STAT3 targeted genes Mcl-1, MMP-2, MMP-9 and VEGF, which are involved
      in cell growth, migration and invasion. Importantly, overexpression of
      constitutively active STAT3 partially rescued the growth inhibiting effects
      induced by quercetin. Furthermore, quercetin suppressed A375 tumor growth and
      STAT3 activities in xenografted mice model, and inhibited murine B16F10 cells
      lung metastasis in an animal model. Overall, these results indicate that the
      antitumor activity of quercetin is at least partially due to inhibition of STAT3
      signaling in melanoma cells. Our findings provided new insight into the action of
      quercetin potently inhibits the STAT3 signaling pathway, suggesting it has a
      potential role in the prevention and treatment of melanoma. 

PMID- 24275162
TI  - The multifunctional autophagy pathway in the human malaria parasite, Plasmodium
      falciparum.
AB  - Autophagy is a catabolic pathway typically induced by nutrient starvation to
      recycle amino acids, but can also function in removing damaged organelles. In
      addition, this pathway plays a key role in eukaryotic development. To date, not
      much is known about the role of autophagy in apicomplexan parasites and more
      specifically in the human malaria parasite Plasmodium falciparum. Comparative
      genomic analysis has uncovered some, but not all, orthologs of autophagy-related
      (ATG) genes in the malaria parasite genome. Here, using a genome-wide in silico
      analysis, we confirmed that ATG genes whose products are required for vesicle
      expansion and completion are present, while genes involved in induction of
      autophagy and cargo packaging are mostly absent. We subsequently focused on the
      molecular and cellular function of P. falciparum ATG8 (PfATG8), an autophagosome
      membrane marker and key component of the autophagy pathway, throughout the
      parasite asexual and sexual erythrocytic stages. In this context, we showed that
      PfATG8 has a distinct and atypical role in parasite development. PfATG8 localized
      in the apicoplast and in vesicles throughout the cytosol during parasite
      development. Immunofluorescence assays of PfATG8 in apicoplast-minus parasites
      suggest that PfATG8 is involved in apicoplast biogenesis. Furthermore, treatment
      of parasite cultures with bafilomycin A 1 and chloroquine, both lysosomotropic
      agents that inhibit autophagosome and lysosome fusion, resulted in dramatic
      morphological changes of the apicoplast, and parasite death. Furthermore, deep
      proteomic analysis of components associated with PfATG8 indicated that it may
      possibly be involved in ribophagy and piecemeal microautophagy of the nucleus.
      Collectively, our data revealed the importance and specificity of the autophagy
      pathway in the malaria parasite and offer potential novel therapeutic strategies.

PMID- 24275164
TI  - Perspective on future role of biological markers in clinical therapy trials of
      Alzheimer's disease: a long-range point of view beyond 2020.
AB  - Recent advances in understanding the molecular mechanisms underlying various
      paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide
      new insight for interventions to modify disease progression. The evolving
      knowledge gained from multidisciplinary basic research has begun to identify new
      concepts for treatments and distinct classes of therapeutic targets; as well as
      putative disease-modifying compounds that are now being tested in clinical
      trials. There is a mounting consensus that such disease modifying compounds
      and/or interventions are more likely to be effectively administered as early as
      possible in the cascade of pathogenic processes preceding and underlying the
      clinical expression of AD. The budding sentiment is that "treatments" need to be
      applied before various molecular mechanisms converge into an irreversible pathway
      leading to morphological, metabolic and functional alterations that characterize
      the pathophysiology of AD. In light of this, biological indicators of
      pathophysiological mechanisms are desired to chart and detect AD throughout the
      asymptomatic early molecular stages into the prodromal and early dementia phase.
      A major conceptual development in the clinical AD research field was the recent
      proposal of new diagnostic criteria, which specifically incorporate the use of
      biomarkers as defining criteria for preclinical stages of AD. This paradigm shift
      in AD definition, conceptualization, operationalization, detection and diagnosis
      represents novel fundamental opportunities for the modification of interventional
      trial designs. This perspective summarizes not only present knowledge regarding
      biological markers but also unresolved questions on the status of surrogate
      indicators for detection of the disease in asymptomatic people and diagnosis of
      AD. 

PMID- 24275165
TI  - Deriving semantic structure from category fluency: clustering techniques and
      their pitfalls.
AB  - Assessing verbal output in category fluency tasks provides a sensitive indicator
      of cortical dysfunction. The most common metrics are the overall number of words
      produced and the number of errors. Two main observations have been made about the
      structure of the output, first that there is a temporal component to it with
      words being generated in spurts, and second that the clustering pattern may
      reflect a search for meanings such that the 'clustering' is attributable to the
      activation of a specific semantic field in memory. A number of sophisticated
      approaches to examining the structure of this clustering have been developed, and
      a core theme is that the similarity relations between category members will
      reveal the mental semantic structure of the category underlying an individual's
      responses, which can then be visualized by a number of algorithms, such as MDS,
      hierarchical clustering, ADDTREE, ADCLUS or SVD. Such approaches have been
      applied to a variety of neurological and psychiatric populations, and the general
      conclusion has been that the clinical condition systematically distorts the
      semantic structure in the patients, as compared to the healthy controls. In the
      present paper we explore this approach to understanding semantic structure using
      category fluency data. On the basis of a large pool of patients with
      schizophrenia (n = 204) and healthy control participants (n = 204), we find that
      the methods are problematic and unreliable to the extent that it is not possible
      to conclude that any putative difference reflects a systematic difference between
      the semantic representations in patients and controls. Moreover, taking into
      account the unreliability of the methods, we find that the most probable
      conclusion to be made is that no difference in underlying semantic representation
      exists. The consequences of these findings to understanding semantic structure,
      and the use of category fluency data, in cortical dysfunction are discussed. 

PMID- 24275166
TI  - Sturge-Weber syndrome: from the past to the present.
AB  - Sturge-Weber syndrome is a rare sporadic neurocutaneous syndrome the hallmark of
      which is a facial port-wine stain involving the first division of the trigeminal
      nerve, ipsilateral leptomeningeal angiomata and angioma involving the ipsilateral
      eye. Our understanding of the disease process has vastly improved since it was
      first described in 1879, with recent identification of an activating somatic
      mutation in the GNAQ gene found in association with both Sturge-Weber syndrome
      and non-syndromic facial port-wine stain. Sturge-Weber syndrome is marked by a
      variable but usually progressive course in early childhood characterised by
      seizures, stroke-like episodes, headaches, neurological and cognitive
      deterioration, hemiparesis, glaucoma and visual field defects. More recently, the
      increased prevalance of otolaryngological, endocrine and emotional-behavioural
      issues have been established. Neurophysiology and neuroimaging studies provide
      information regarding the evolution of changes in Sturge-Weber syndrome over
      time. Early recognition and aggressive management of symptoms remains cornerstone
      in the management of this syndrome. An international collaborative effort is
      needed to maximise our understanding of the natural history and response to
      interventions in Sturge-Weber Syndrome. 

PMID- 24275167
TI  - Emerging drugs of abuse.
AB  - Many new emerging drugs of abuse are marketed as legal highs despite being
      labeled "not for human consumption" to avoid regulation. The availability of
      these substances over the Internet and in "head shops" has lead to a multitude of
      emergency department visits with severe complications including deaths worldwide.
      Despite recent media attention, many of the newer drugs of abuse are still
      largely unknown by health care providers. Slight alterations of the basic
      chemical structure of substances create an entirely new drug no longer regulated
      by current laws and an ever-changing landscape of clinical effects. The purity of
      each substance with exact pharmacokinetic and toxicity profiles is largely
      unknown. Many of these substances can be grouped by the class of drug and
      includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well
      as piperazine derivatives. Resultant effects generally include psychoactive and
      sympathomimetic-like symptoms. Additionally, prescription medications,
      performance enhancing medications, and herbal supplements are also becoming more
      commonly abused. Most new drugs of abuse have no specific antidote and management
      largely involves symptom based goal directed supportive care with benzodiazepines
      as a useful adjunct. This paper will focus on the history, epidemiology, clinical
      effects, laboratory analysis, and management strategy for many of these emerging
      drugs of abuse.

PMID- 24275168
TI  - Pediatric toxicology: specialized approach to the poisoned child.
AB  - The poisoned child presents unique considerations in circumstances of exposure,
      clinical effects, diagnostic approach, and therapeutic interventions. The
      emergency provider must be aware of the pathophysiologic vulnerabilities of
      infants and children and substances that are especially toxic. Awareness is
      essential for situations in which the risk of morbidity and mortality is
      increased, such as child abuse by poisoning. Considerations in treatment include
      the need for attentive supportive care, pediatric implications for antidotal
      therapy, and extracorporeal removal methods such as hemodialysis in children. In
      this article, each of these issues and emerging poison hazards are discussed. 

PMID- 24275169
TI  - Toxin-induced coagulopathy.
AB  - Although warfarin and heparin have been mainstays of anticoagulation for almost
      50 years, the recent introduction of multiple oral anticoagulants has led some
      practitioners to shift away from warfarin as the anticoagulant of choice for
      various diseases. Major advances have been made in targeting downstream clotting
      factors in the coagulation cascade, resulting in two major new classes of drugs:
      direct thrombin inhibitors and factor Xa inhibitors. Developed partially with the
      patient in mind, these drugs are taken orally and, because of their target
      specificity, have eliminated the need for routine blood monitoring, making them
      attractive to patients currently on warfarin.

PMID- 24275170
TI  - Toxin-induced cardiovascular failure.
AB  - Adverse cardiovascular events comprise a large portion of the morbidity and
      mortality in drug overdose emergencies. Adverse cardiovascular events encountered
      by emergency physicians treating poisoned patients include myocardial injury,
      hemodynamic compromise with shock, tachydysrhythmias, and cardiac arrest. Early
      signs of toxin-induced cardiovascular failure include bradycardia, tachycardia,
      and specific ECG findings. Treatment of toxicologic tachycardia relies on rapid
      supportive care along with proper use of benzodiazepines for sedation. Treatment
      of toxicologic bradycardia consists of the use of isotonic fluids, atropine,
      calcium salts, and glucagon. High-dose insulin euglycemia should be used early in
      the course of suspected severe poisoning and intravenous lipid emulsion given to
      patients who suffer cardiac arrest.

PMID- 24275171
TI  - Toxin-induced hepatic injury.
AB  - Toxins such as pharmaceuticals, herbals, foods, and supplements may lead to
      hepatic damage. This damage may range from nonspecific symptoms in the setting of
      liver test abnormalities to acute hepatic failure. The majority of severe cases
      of toxin-induced hepatic injury are caused by acetaminophen and ethanol. The most
      important step in the patient evaluation is to gather an extensive history that
      includes toxin exposure and exclude common causes of liver dysfunction. Patients
      whose hepatic dysfunction progresses to acute liver failure may benefit from
      transfer to a transplant service for further management. Currently, the mainstay
      in management for most exposures is discontinuing the offending agent. This
      manuscript will review the incidence, pathophysiology, diagnosis and management
      of the different forms of toxin-induced hepatic injury and exam in-depth the most
      common hepatic toxins.

PMID- 24275172
TI  - Toxin-induced respiratory distress.
AB  - This article describes the impact of various toxic substances on the airway and
      pulmonary system. Pulmonary anatomy and physiology provide the basis for
      understanding the response to toxin-induced injury. Simple asphyxiants displace
      oxygen from the inspired air. Respiratory irritants include water-soluble and
      water-insoluble compounds. Several inhaled agents produce direct airway injury,
      which may be mediated by caustic, thermal, and hydrocarbon exposures. Unique
      pulmonary toxins and toxicants are discussed, as well as inhaled toxin mixtures.
      Several inhaled toxins may also impair oxygen transport. The pulmonary system may
      also provide a mechanism for systemic toxin delivery on respiratory exposure.

PMID- 24275173
TI  - Toxicologic acid-base disorders.
AB  - Acid-base disorders may complicate the presentation of patients with poisoning.
      This article summarizes an approach to acid-base disorders from a toxicologic
      perspective. It aims to assist the reader in identifying underlying acid-base
      processes, generating a differential diagnosis for each, and approaching that
      differential diagnosis in a systematic fashion. Understanding these processes
      will help to guide management and interventional strategies. 

PMID- 24275174
TI  - An approach to chemotherapy-associated toxicity.
AB  - The effects of chemotherapy in multiple organ systems may be challenging to
      discern from the sequelae of malignancy and systemic illnesses with concomitant
      immunocompromise. Chemotherapeutic agents typically affect multiple organ
      systems. Intrathecal medication errors may pose particularly devastating
      neurologic consequences and death, often requiring emergent intervention. This
      article provides an overview of commonly used chemotherapeutic drugs, indications
      for use, their adverse effects by organ system, and the management of commonly
      encountered toxicities. Intrathecal medication errors and specific antidotes are
      discussed in pertinent management sections. Emergency department management
      should focus on rapid patient assessment, immediate intervention following
      intrathecal medication errors, exclusion of infection, and excellent supportive
      care.

PMID- 24275175
TI  - Central nervous system toxicity.
AB  - Central nervous system toxicity caused by xenobiotic exposure is a common reason
      for presentation to the emergency department. Sources of exposure may be
      medicinal, recreational, environmental, or occupational; the means of exposure
      may be intentional or unintended. Toxicity may manifest as altered thought
      content resulting in psychosis or confusion; may affect arousal, resulting in
      lethargy, stupor, or coma; or may affect both elements of consciousness. Seizures
      may also occur.

PMID- 24275176
TI  - Marine envenomations.
AB  - This article describes the epidemiology and presentation of human envenomation
      from marine organisms. Venom pathophysiology, envenomation presentation, and
      treatment options are discussed for sea snake, stingray, spiny fish, jellyfish,
      octopus, cone snail, sea urchin, and sponge envenomation. The authors describe
      the management of common exposures that cause morbidity as well as the keys to
      recognition and treatment of life-threatening exposures. 

PMID- 24275177
TI  - Ionizing radiation injuries and illnesses.
AB  - Although the spectrum of information related to diagnosis and management of
      radiation injuries and illnesses is vast and as radiation contamination incidents
      are rare, most emergency practitioners have had little to no practical experience
      with such cases. Exposures to ionizing radiation and internal contamination with
      radioactive materials can cause significant tissue damage and conditions.
      Emergency practitioners unaware of ionizing radiation as the cause of a condition
      may miss the diagnosis of radiation-induced injury or illness. This article
      reviews the pertinent terms, physics, radiobiology, and medical management of
      radiation injuries and illnesses that may confront the emergency practitioner.

PMID- 24275178
TI  - Clinical toxicology.

PMID- 24275179
TI  - Clinical toxicology. Preface.

PMID- 24275180
TI  - Estrogen modulates cardiac growth through an estrogen receptor alpha-dependent
      mechanism in healthy ovariectomized mice.
AB  - The modulation of cardiac growth by estrogen in healthy mice is not completely
      understood. The aim was to investigate the effects of estrogen on cardiac growth
      in healthy mice lacking either estrogen receptor (ER) alpha or beta. Wild-type
      (WT), ERalpha knockout (ERKO) and ERbeta knockout (BERKO) 2-month-old mice were
      ovariectomized and randomly assigned to groups receiving an estradiol (E2)
      containing or soy-free (control, CON) diet (n=5-7/group). After three months of
      E2 administration, WT and BERKO mice had significantly lower body weight, higher
      relative uterus and heart weight than CON mice, while there was no major E2
      effect in ERKO mice. Furthermore, there was a higher concentration of E2
      responsive genes Igf1 and Myocd in WT and BERKO but not in ERKO mice. Together,
      these findings indicate that the estrogenic regulation of cardiac growth in
      healthy mice is primarily mediated through ERalpha and not ERbeta. 

PMID- 24275181
TI  - Real-time trafficking and signaling of the glucagon-like peptide-1 receptor.
AB  - The glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein
      coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its
      regulatory effect on post-prandial blood-glucose levels. The mechanism(s)
      controlling GLP-1R mediated signaling are far from fully understood. A
      fundamental mechanism controlling the signaling capacity of GPCRs is the post
      endocytic trafficking of receptors between recycling and degradative fates. Here,
      we combined microscopy with novel real-time assays to monitor both receptor
      trafficking and signaling in living cells. We find that the human GLP-1R
      internalizes rapidly and with similar kinetics in response to equipotent
      concentrations of GLP-1 and the stable GLP-1 analogues exendin-4 and liraglutide.
      Receptor internalization was confirmed in mouse pancreatic islets. GLP-1R is
      shown to be a recycling receptor with faster recycling rates mediated by GLP-1 as
      compared to exendin-4 and liraglutide. Furthermore, a prolonged cycling of ligand
      activated GLP-1Rs was observed and is suggested to be correlated with a prolonged
      cAMP signal. 

PMID- 24275183
TI  - Pomegranate anaphylaxis due to cross-reactivity with Peach LTP (Pru p 3).

PMID- 24275182
TI  - Hypoxia induces a HIF-1alpha dependent signaling cascade to make a complex
      metabolic switch in SGBS-adipocytes.
AB  - To elucidate the complex impact of hypoxia on adipose tissue, resulting in biased
      metabolism, insulin resistance and finally diabetes we used mature adipocytes
      derived from a Simpson-Golabi-Behmel syndrome patient for microarray analysis. We
      found a significantly increased transcription rate of genes involved in
      glycolysis and a striking association between the pattern of upregulated genes
      and disease biomarkers for diabetes mellitus and insulin resistance. Although
      their upregulation turned out to be HIF-1alpha-dependent, we identified further
      transcription factors mainly AP-1 components to play also an important role in
      hypoxia response. Analyzing the regulatory network of mentioned transcription
      factors and glycolysis targets we revealed a clear hint for directing glycolysis
      to glutathione and glycogen synthesis. This metabolic switch in adipocytes
      enables the cell to prevent oxidative damage in the short term but might induce
      lipogenesis and establish systemic metabolic disorders in the long run. 

PMID- 24275184
TI  - Serotonin 1A receptors and sexual behavior in female rats: a review.
AB  - This review focuses on the role of serotonin and especially 5-HT1A receptors in
      female rat sexual behavior. In addition, the differences and/or similarities with
      male rats are discussed. Overall, in both males and females 5-HT1A receptors do
      not appear to be involved in sexual behavior under normal circumstances, but
      become very important under conditions of elevated serotonin levels. 5-HT1A
      receptor agonists facilitate sexual behavior in male rats, but inhibit female
      sexual activity. At first sight, this seems quite conflicting, but could be due
      to our definitions of different elements of sexual behavior. Three different
      phases can be distinguished in rats' sexual cycle, the introductory
      (precopulatory), the copulatory and the executive (ejaculatory) phases. Different
      mechanisms and brain regions are involved in these phases. If the appropriate
      phases of males and females are properly compared, the role of 5-HT1A receptors
      in rats might be more similar than assumed thus far.

PMID- 24275186
TI  - Pitfalls in hormone determinations.

PMID- 24275185
TI  - Adolescent binge ethanol treatment alters adult brain regional volumes, cortical
      extracellular matrix protein and behavioral flexibility.
AB  - Adolescents binge drink more than any other age group, increasing risk of
      disrupting the development of the frontal cortex. We hypothesized that adolescent
      binge drinking would lead to persistent alterations in adulthood. In this study,
      we modeled adolescent weekend underage binge-drinking, using adolescent mice
      (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE)
      treatment includes 6 binge intragastric doses of ethanol in an intermittent
      pattern across adolescence. Assessments were conducted in adulthood following
      extended abstinence to determine if there were persistent changes in adults.
      Reversal learning, open field and other behavioral assessments as well as brain
      structure using magnetic imaging and immunohistochemistry were determined. We
      found that AIE did not impact adult Barnes Maze learning. However, AIE did cause
      reversal learning deficits in adults. AIE also caused structural changes in the
      adult brain. AIE was associated with adulthood volume enlargements in specific
      brain regions without changes in total brain volume. Enlarged regions included
      the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal
      capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in
      adults after AIE is consistent with previous imaging studies in human
      adolescents. AIE treatment was associated with significant increases in the
      expression of several extracellular matrix (ECM) proteins in the adult OFC
      including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP
      (5%). These findings are consistent with AIE causing persistent changes in brain
      structure that could contribute to a lack of behavioral flexibility. 

PMID- 24275187
TI  - Pitfalls in the measurement and interpretation of thyroid function tests.
AB  - Thyroid function tests (TFTs) are amongst the most commonly requested laboratory
      investigations in both primary and secondary care. Fortunately, most TFTs are
      straightforward to interpret and confirm the clinical impression of euthyroidism,
      hypothyroidism or hyperthyroidism. However, in an important subgroup of patients
      the results of TFTs can seem confusing, either by virtue of being discordant with
      the clinical picture or because they appear incongruent with each other [e.g.
      raised thyroid hormones (TH), but with non-suppressed thyrotropin (TSH); raised
      TSH, but with normal TH]. In such cases, it is important first to revisit the
      clinical context, and to consider potential confounding factors, including
      alterations in normal physiology (e.g. pregnancy), intercurrent (non-thyroidal)
      illness, and medication usage (e.g. thyroxine, amiodarone, heparin). Once these
      have been excluded, laboratory artefacts in commonly used TSH or TH immunoassays
      should be screened for, thus avoiding unnecessary further investigation and/or
      treatment in cases where there is assay interference. In the remainder,
      consideration should be given to screening for rare genetic and acquired
      disorders of the hypothalamic-pituitary-thyroid (HPT) axis [e.g. resistance to
      thyroid hormone (RTH), thyrotropinoma (TSHoma)]. Here, we discuss the main
      pitfalls in the measurement and interpretation of TFTs, and propose a structured
      algorithm for the investigation and management of patients with
      anomalous/discordant TFTs.

PMID- 24275188
TI  - Determination of insulin for the diagnosis of hyperinsulinemic hypoglycemia.
AB  - Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia
      in children and adults. The diagnosis of hyperinsulinemic hypoglycemia relies on
      the evaluation of the biochemical profile at the time of hypoglycemia, however,
      contrary to common perception, plasma insulin is not always elevated. Thus, the
      diagnosis must often be based on the examination of other physiologic
      manifestations of excessive insulin secretion, such as suppression of
      glycogenolysis, lipolysis and ketogenesis, which can be inferred by the finding
      of a glycemic response to glucagon, and the suppression of plasma free fatty
      acids and beta-hydroxybutyrate concentrations during hypoglycemia.

PMID- 24275189
TI  - Determination of IGFs and their binding proteins.
AB  - The worldwide clinical and scientific interest in peptides belonging to the
      insulin-like growth factor (IGF) system has brought along a call for
      standardization of assays used to quantify the different IGF related proteins.
      This relates in particular to the measurement of IGF-I, which has stood the test
      of time as an important biochemical tool in the diagnosis and treatment of growth
      hormone (GH) related disorders. The first international consensus statement on
      the measurement of IGF-I in 2011 represents an important milestone and will
      undoubtedly improve commutability of reference ranges for IGF-I and clinically
      applicable cut-off values. By contrast, there is no consensus addressing the
      measurements of the other IGF-related peptides. Nevertheless, measurement of
      these peptides may be of interest, either as additional tools in GH disorders or
      as prognostic biomarkers of various diseases. Therefore, standardization of
      assays for the other IGF-related peptides is highly relevant. This chapter
      discusses the recent consensus on IGF-I measurements and how this approach may be
      applied to measurement of the other IGF-related peptides. In addition, assay
      pitfalls, pre- and post-analytical challenges, alternative methods for IGF-I
      measurements and potential assays of tomorrow will be discussed.

PMID- 24275190
TI  - Determination of human chorionic gonadotropin.
AB  - Determination of human chorionic gonadotropin (hCG) is used for diagnosis and
      monitoring of pregnancy, pregnancy related disorders, for trophoblastic and some
      nontrophoblastic tumors. In addition, hCG is determined for doping control in
      males. Assay of hCG is complicated by the occurrence of different molecular
      forms, which are detected to various degrees by different assays. The main form
      of hCG in circulation and in patients with trophoblastic tumors is intact
      heterodimeric hCG. The free beta subunit (hCGbeta) is a minor form in plasma in
      both conditions, but it may be the major form aggressive trophoblastic cancer.
      Therefore, assays measuring hCG and hCGbeta together are mainly used for
      diagnosis of pregnancy and trophoblastic diseases. When excreted into urine, most
      of hCG (and hCGbeta) is broken down to the core fragment of hCGbeta (hCGbetacf),
      which is the main immunoreactive form of hCG in urine during pregnancy. Specific
      determination of hCGbeta is of value in screening for Down's syndrome and
      diagnosis of nontrophoblastic cancer. hCGbcf is of limited utility but it is
      important because it may disturb assay of hCG in pregnancy.

PMID- 24275191
TI  - Determination of cortisol in serum, saliva and urine.
AB  - Cortisol is quantitatively the major glucocorticoid product of the adrenal
      cortex. The main reason to measure cortisol is to diagnose human diseases
      characterised by deficiency of adrenal steroid excretion in Addison's disease or
      overproduction in Cushing's syndrome (CS). In both cases a sensitive, accurate
      and reproducible assay of cortisol is required. Several methods have been
      described for the quantitative measurement of cortisol in both serum and urine.
      The most widely used methods in routine clinical laboratories are immunoassays
      (IA) and enzyme immunoassays (EIA), luminescence and fluorescence assays, which
      are available in numerous commercial kits and on automated platforms. However,
      there remains a number of problems in the so-called direct immunoassays if
      extraction and prepurification are not carried out before the assay. Recently,
      more specific chromatographic methods have been introduced, such as high pressure
      liquid chromatographic (HPLC) or liquid chromatography tandem mass spectrometric
      assays (LC-MS/MS). The high specificity especially of LC-MS/MS facilitates
      reliable measurement of cortisol both in plasma, urine and saliva samples.

PMID- 24275192
TI  - External quality assessment of hormone determinations.
AB  - Hormone determinations are of central importance to the practice of Clinical
      Endocrinology, and ensuring their correct use and performance is a
      multidisciplinary responsibility involving clinicians, laboratory staff,
      manufacturers of diagnostic systems and healthcare regulatory agencies. All these
      professional groups have, therefore, an interest in external quality assessment
      (EQA) as an audit tool that can identify areas where use of tests in routine
      practice requires improvement to reduce risks to patients. This chapter reviews
      the principles of EQA, and outlines its strengths and limitations, illustrated
      with example data from the UK National External Quality Assessment Service (UK
      NEQAS). The immunological nature of many hormone assays, often further
      complicated by heterogeneity of analyte structure and lack of suitable
      calibrators, presents special problems for the designers of EQA schemes in
      ensuring that specimens are appropriate and that target values are accurate.
      Laboratory users of EQA should have sufficient knowledge of the characteristics
      of the EQA schemes in which they participate to make informed interpretation of
      their data. The trend since the 1980s for in-house assays designed in individual
      laboratories to be superseded by automated assays provided by a small number of
      diagnostics manufacturers places a special responsibility on manufacturers to
      ensure reliable assay design and calibration. In collaboration with other parties
      EQA can help identify priorities for improved assay design and calibration.
      Although traditionally the focus of EQA has been on assessing the analytical
      phase it can also make some assessment of other important aspects of performance,
      e.g. the consistency of reference ranges and how results are interpreted.
      Overall, EQA has a valuable role both in laboratory accreditation and as an
      educational resource, thereby helping to ensure and improve the quality of
      laboratory services that support patient care.

PMID- 24275193
TI  - Standardization of hormone determinations.
AB  - Standardization of hormone determinations is important because it simplifies
      interpretation of results and facilitates the use of common reference values for
      different assays. Progress in standardization has been achieved through the
      introduction of more homogeneous hormone standards for peptide and protein
      hormones. However, many automated methods for determinations of steroid hormones
      do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS)
      has been used to establish reference methods for steroid hormone determinations
      and is now increasingly used for routine determinations of steroids and other low
      molecular weight compounds. Reference methods for protein hormones based on MS
      are being developed and these promise to improve standardization.

PMID- 24275194
TI  - Age-related changes in thyroid hormone levels of bonobos and chimpanzees indicate
      heterochrony in development.
AB  - We present information on age related changes of thyroid hormone levels in
      bonobos (N = 96) and chimpanzees (N = 100) ranging between one and 56 years of
      age. Fresh urine samples were used for hormone measurements with a commercial
      competitive total triiodothyronine (T3) ELISA. In both species, immature
      individuals had higher TT3 levels than adults and there was a marked decrease in
      TT3 levels between age classes. The two species differed in terms of the timing
      of TT3 level changes, with chimpanzees experiencing a significant decline in TT3
      levels after 10 years of age and bonobos after 20 years of age. The decline of
      TT3 in chimpanzees appears to coincide with the time when somatic growth
      terminates while TT3 values in bonobos decrease much later. This temporal
      asymmetry in urinary thyroid hormone levels indicates heterochrony in the
      ontogenetic changes of the two sister species and developmental delay in bonobos.
      The prolongation of high TT3 levels in bonobos, which is characteristic of
      immatures of both Pan species may affect the behavior of bonobos; namely, the low
      intensity of aggression they display. Given that developmental studies are often
      based on post-mortem analyses of skeletons, measures of urinary thyroid hormones
      offer a non-invasive tool for exploring ontogenetic changes in living wild and
      captive hominoids. 

PMID- 24275195
TI  - Preparation of ZnS:Ni/ZnS quantum dots with core/shell structure and application
      for detecting cefoperazone-sulbactam.
AB  - ZnS:Ni quantum dots (QDs) have been synthesized via a water-soluble route, which
      were coated by ZnS shell through surface modification to give ZnS:Ni/ZnS QDs. The
      QDs were characterized by atomic force microscope, X-ray diffraction, infrared
      spectrometry and fluorescent spectrometry. Then, a novel method for the
      determination of cefoperazone-sulbactam (CPZ-SBT) in aqueous solutions has been
      developed based on the enhancement of fluorescence of ZnS:Ni/ZnS QDs in the
      presence of CPZ-SBT. Under the optimal conditions, the enhanced fluorescence
      intensity (DeltaF) was proportional to CPZ-SBT concentration in the range of
      8.0*10(-6)-1.0*10(-4) g/L with a detection limit of 1.0*10(-7) g/L. The method
      was employed for the determination of CPZ-SBT in sample to give satisfactory
      result. Compared with others, this method was more sensitive, fast and simple
      with low limit detection.

PMID- 24275197
TI  - The contribution of different frequency bands of fMRI data to the correlation
      with EEG alpha rhythm.
AB  - Alpha rhythm is a prominent EEG rhythm observed during resting state and is
      thought to be related to multiple cognitive processes. Previous simultaneous
      electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) studies
      have demonstrated that alpha rhythm is associated with blood oxygen level
      dependent (BOLD) signals in several different functional networks. How these
      networks influence alpha rhythm respectively is unclear. The low-frequency
      oscillations (LFO) in spontaneous BOLD activity are thought to contribute to the
      local correlations in resting state. Recent studies suggested that either LFO or
      other components of fMRI can be further divided into sub-components on different
      frequency bands. We hypothesized that those BOLD sub-components characterized the
      contributions of different brain networks to alpha rhythm. To test this
      hypothesis, EEG and fMRI data were simultaneously recorded from 17 human subjects
      performing an eyes-close resting state experiment. EEG alpha rhythm was
      correlated with the filtered fMRI time courses at different frequency bands (0.01
      0.08 Hz, 0.08-0.25 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198
      0.25 Hz). The results demonstrated significant relations between alpha rhythm and
      the BOLD signals in the visual network and in the attention network at LFO band,
      especially at the very low frequency band (0.01-0.027 Hz).

PMID- 24275196
TI  - Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF
      mediated protection from hypoxia.
AB  - Carbonic anhydrases (CAs) comprise a family of zinc-containing enzymes that
      catalyze the reversible hydration of carbon dioxide. CAs contribute to a myriad
      of physiological processes, including pH regulation, anion transport and water
      balance. To date, 16 known members of the mammalian alpha-CA family have been
      identified. Given that the catalytic family members share identical reaction
      chemistry, their physiologic roles are influenced greatly by their tissue and sub
      cellular locations. CAVI is the lone secreted CA and exists in both saliva and
      the gastrointestinal mucosa. An alternative, stress-inducible isoform of CAVI
      (CAVI-b) has been shown to be expressed from a cryptic promoter that is activated
      by the CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP). The CAVI-b
      isoform is not secreted and is currently of unknown physiological function. Here
      we use neuronal models, including a model derived using Car6 and CHOP gene
      ablations, to delineate a role for CAVI-b in ischemic protection. Our results
      demonstrate that CAVI-b expression, which is increased through CHOP-signaling in
      response to unfolded protein stress, is also increased by oxygen-glucose
      deprivation (OGD). While enforced expression of CAVI-b is not sufficient to
      protect against ischemia, CHOP regulation of CAVI-b is necessary for adaptive
      changes mediated by BDNF that reduce subsequent ischemic damage. These results
      suggest that CAVI-b comprises a necessary component of a larger adaptive
      signaling pathway downstream of CHOP. 

PMID- 24275198
TI  - Neuroprotection by genipin against reactive oxygen and reactive nitrogen species
      mediated injury in organotypic hippocampal slice cultures.
AB  - Genipin, the multipotent ingredient in Gardenia jasmenoides fruit extract (GFE),
      may be an effective candidate for treatment following stroke or traumatic brain
      injury (TBI). Secondary injury includes damage mediated by reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), which can alter the biological
      function of key cellular structures and eventually lead to cell death. In this
      work, we studied the neuroprotective potential of genipin against damage stemming
      from ROS and RNS production in organotypic hippocampal slice cultures (OHSC), as
      well as its potential as a direct free radical scavenger. A 50 uM dose of genipin
      provided significant protection against tert-butyl hydroperoxide (tBHP), a
      damaging organic peroxide. This dosage of genipin significantly reduced cell
      death at 48 h compared to vehicle control (0.1% DMSO) when administered 0, 1, 6,
      and 24 h after addition of tBHP. Similarly, genipin significantly reduced cell
      death at 48 h when administered 0, 1, 2, and 6h after addition of rotenone, which
      generates reactive oxygen species via a more physiologically relevant mechanism.
      Furthermore, genipin significantly reduced both cell death and nitrite levels at
      24 h caused by S-nitroso-N-acetylpenicillamine (SNAP), a direct nitric oxide (NO)
      donor, and successfully quenched 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), a stable
      free radical, suggesting that genipin may act as a direct free radical scavenger.
      Our encouraging findings suggest that genipin should be tested in animal models
      of CNS injury with a significant component of ROS- and RNS-mediated damage, such
      as TBI and stroke, to assess its in vivo efficacy.

PMID- 24275199
TI  - Motor neuron expression of the voltage-gated calcium channel cacophony restores
      locomotion defects in a Drosophila, TDP-43 loss of function model of ALS.
AB  - Dysfunction of the RNA-binding protein, TDP-43, is strongly implicated as a
      causative event in many neurodegenerative diseases including amyotrophic lateral
      sclerosis (ALS). TDP-43 is normally found in the nucleus and pathological
      hallmarks of ALS include the presence of cytoplasmic protein aggregates
      containing TDP-43 and an associated loss of TDP-43 from the nucleus. Loss of
      nuclear TDP-43 likely contributes to neurodegeneration. Using Drosophila
      melanogaster to model TDP-43 loss of function, we show that reduced levels of the
      voltage-gated calcium channel, cacophony, mediate some of the physiological
      effects of TDP-43 loss. Null mutations in the Drosophila orthologue of TDP-43,
      named TBPH, resulted in defective larval locomotion and reduced levels of
      cacophony protein in whole animals and at the neuromuscular junction. Restoring
      the levels of cacophony in all neurons or selectively in motor neurons rescued
      these locomotion defects. Using TBPH immunoprecipitation, we showed that TBPH
      associates with cacophony transcript, indicating that it is likely to be a direct
      target for TBPH. Loss of TBPH leads to reduced levels of cacophony transcript,
      possibly due to increased degradation. In addition, TBPH also appears to regulate
      the inclusion of some alternatively spliced exons of cacophony. If similar
      effects of cacophony or related calcium channels are found in human ALS patients,
      these could be targets for the development of pharmacological therapies for ALS.

PMID- 24275200
TI  - Control over band structure and tunneling in bilayer graphene induced by velocity
      engineering.
AB  - The band structure and transport properties of massive Dirac fermions in bilayer
      graphene with velocity modulation in space are investigated in the presence of a
      previously created band gap. It is pointed out that velocity engineering may be
      considered as a factor to control the band gap of symmetry-broken bilayer
      graphene. The band gap is direct and independent of velocity value if the
      velocity modulated in two layers is set up equally. Otherwise, in the case of
      interlayer asymmetric velocity, not only is the band gap indirect, but also the
      electron-hole symmetry fails. This band gap is controllable by the ratio of the
      velocity modulated in the upper layer to the velocity modulated in the lower
      layer. In more detail, the shift of momentum from the conduction band edge to the
      valence band edge can be engineered by the gate bias and velocity ratio. A
      transfer matrix method is also elaborated to calculate the four-band coherent
      conductance through a velocity barrier possibly subjected to a gate bias.
      Electronic transport depends on the ratio of velocity modulated inside the
      barrier to that for surrounding regions. As a result, a quantum version of total
      internal reflection is observed for thick enough velocity barriers. Moreover, a
      transport gap originating from the applied gate bias is engineered by modulating
      the velocities of the carriers in the upper and lower layers. 

PMID- 24275201
TI  - Unidirectional laning and migrating cluster crystals in confined self-propelled
      particle systems.
AB  - One standard approach to describe the collective behaviour of self-propelled
      particles is the Vicsek model: point-like self-propelled particles tend to align
      their migration directions to the ones of their nearer neighbours at each time
      step. Here we use a variant of the Vicsek model that includes pairwise repulsive
      interactions. Confining the system between parallel walls can qualitatively
      change its appearance: a laning state can emerge that is different from the ones
      previously reported. All lanes show on average the same migration direction of
      the contained particles with a finite separation distance between the lanes.
      Furthermore, in certain parameter ranges we observe collectively migrating
      clusters that arrange in an approximately hexagonal way. We suggest that the
      mechanism behind these regular textures is an overreaction in the alignment
      mechanism. Considering the more realistic scenario of non-point-like particles in
      the presence of confining surfaces is generally important for the comparison to
      experimental systems. 

PMID- 24275202
TI  - Significant impact of patient age on outcome after liver resection for HCC in
      cirrhosis.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumors worldwide. The majority of patients with HCC have cirrhosis. Beside liver
      transplantation the resection is an established curative treatment option for
      patients with HCC in cirrhosis. However, the long term success is limited by a
      high tumor recurrence rate. Furthermore, by many patients surgical resection is
      restricted by poor liver function. The purpose of this study was to investigate
      the influence of patient age on long term outcome after liver resection in
      patients with HCC in cirrhotic liver. Further purpose was to define the potential
      prognostic factors. PATIENTS AND METHODS: The outcome of 141 patients with liver
      cirrhosis after curative resection was analyzed using a prospective database.
      Only patients with postoperative histological assurance of HCC were included in
      the database. Patients with fibrolamellar HCC were excluded. RESULTS: By patients
      below 70 years of age the 1-, 3- and 5-year survival rates were 78.5%, 56.5% and
      47.1%. By patients over 70 years the 1-, 3- and 5-year survival rates were 59.9%,
      40.3% and 6.7%. Cumulative survival of the total collective was significant
      influenced by patient age, Clavien grade, positive lymph vessels, mechanical
      ventilation and BMI. The overall postoperative morbidity was 44.7%. No
      intraoperative deaths were observed, but 11 patients (8 older than 70 and 3
      younger than 70 years) died during the hospital stay. Clavien grade correlated
      with preoperative increased GGT, need for intraoperative blood and fresh frozen
      plasma transfusion. CONCLUSIONS: Patient age and postoperative complications are
      more relevant for the outcome than many tumor factors, especially by patients
      over 70 years of age. In contrast, the prognosis of patients below 70 years of
      age is significantly better and a 5 year survival rate above 50% could be shown
      in our patients. However, by carefully selected elderly patients with HCC in
      cirrhosis an acceptable long term survival is reachable.

PMID- 24275203
TI  - Appendiceal adenocarcinoma in a patient with chronic ulcerative colitis: what is
      the appropriate surgical procedure?

PMID- 24275204
TI  - Predictive factors for clinically actionable computed tomography findings in
      inflammatory bowel disease patients seen in the emergency department with acute
      gastrointestinal symptoms.
AB  - BACKGROUND: The wide use of abdomino-pelvic computed tomography (APCT) in
      emergency departments (ED) has raised the concern for radiation exposure, costs
      and potential reactions to contrast agents. The aim of this study was to
      determine the yield and predictive factors for clinically actionable findings
      (CAF) in APCTs performed in patients with inflammatory bowel disease (IBD) who
      visit the ED. METHODS: We performed a cross-sectional study including patients
      with IBD who visited the ED. Variables considered were demographics, IBD
      phenotype, clinical symptoms, IBD medication use prior to ED visit, laboratory
      values, and imaging results. The primary outcome was a composite of CAF, defined
      as new, intra-abdominal abscess or tumor, bowel obstruction, fistulae,
      diverticulitis, choledocholithiasis, or appendicitis. RESULTS: 354 patients were
      included. One or more CAF were reported in 26.6% of the APCTs (32.1% in CD and
      12.8% in UC [p<0.01]). Independent predictive variables of CAF in CD were: CRP
      level >=5mg/dl (p=0.04), previous history of IBD surgery (p=0.037), Black race
      (p<0.01) and low body mass index (p<0.01). None of the study variables predicted
      CAF in UC. CONCLUSIONS: The yield for CAF with APCT in the ED was high for CD
      patients but minimal for those with UC and was not improved by the use of
      contrast. Elevated CRP, low BMI, Black race and previous history of IBD surgery
      predicted CAF in CD but no variables were predictive of CAF in UC.

PMID- 24275205
TI  - Mapping the economic benefits to livestock keepers from intervening against
      bovine trypanosomosis in Eastern Africa.
AB  - Endemic animal diseases such as tsetse-transmitted trypanosomosis are a constant
      drain on the financial resources of African livestock keepers and on the
      productivity of their livestock. Knowing where the potential benefits of removing
      animal trypanosomosis are distributed geographically would provide crucial
      evidence for prioritising and targeting cost-effective interventions as well as a
      powerful tool for advocacy. To this end, a study was conducted on six tsetse
      infested countries in Eastern Africa: Ethiopia, Kenya, Somalia, South Sudan,
      Sudan and Uganda. First, a map of cattle production systems was generated, with
      particular attention to the presence of draught and dairy animals. Second, herd
      models for each production system were developed for two scenarios: with or
      without trypanosomosis. The herd models were based on publications and reports on
      cattle productivity (fertility, mortality, yields, sales), from which the income
      from, and growth of cattle populations were estimated over a twenty-year period.
      Third, a step-wise spatial expansion model was used to estimate how cattle
      populations might migrate to new areas when maximum stocking rates are exceeded.
      Last, differences in income between the two scenarios were mapped, thus providing
      a measure of the maximum benefits that could be obtained from intervening against
      tsetse and trypanosomosis. For this information to be readily mappable, benefits
      were calculated per bovine and converted to US$ per square kilometre. Results
      indicate that the potential benefits from dealing with trypanosomosis in Eastern
      Africa are both very high and geographically highly variable. The estimated total
      maximum benefit to livestock keepers for the whole of the study area amounts to
      nearly US$ 2.5 billion, discounted at 10% over twenty years--an average of
      approximately US$ 3300 per square kilometre of tsetse-infested area--but with
      great regional variation from less than US$ 500 per square kilometre to well over
      US$ 10,000. The greatest potential benefits accrue to Ethiopia, because of its
      very high livestock densities and the importance of animal traction, but also to
      parts of Kenya and Uganda. In general, the highest benefit levels occur on the
      fringes of the tsetse infestations. The implications of the models' assumptions
      and generalisations are discussed.

PMID- 24275206
TI  - GAMT deficiency: 20 years of a treatable inborn error of metabolism.

PMID- 24275207
TI  - Knowledge, attitudes and practices of physicians and nurses regarding the link
      between IVF treatments and breast cancer.
AB  - PURPOSE: The ovarian stimulating hormones used in In-Vitro Fertilization may
      increase the incidence of breast cancer. Little research has been conducted to
      ascertain health professionals' knowledge or practices regarding this possible
      connection and if they communicate this risk to their patients. This study
      described the knowledge, attitudes and practices of doctors and nurses regarding
      the causative link between In-Vitro Fertilization treatments and breast cancer,
      and to determine if these health professionals were assessing or communicating
      this possible risk to their patients. METHOD: Seventy gynecologists and nurses
      who worked in fertility clinics, had at least one year of experience in fertility
      and were literate in Hebrew were asked to complete the questionnaires. Ten
      clinics around the country were contacted and the questionnaires were distributed
      and collected on the same day. RESULTS: 35 Nurses and 35 gynecologists completed
      the survey. Although the majority of the physicians (68%) and nurses (69%)
      thought that there was a possible connection between the hormonal treatment of
      IVF and breast cancer, physicians were significantly more likely to inform their
      patients about the connection than were nurses. CONCLUSIONS: There is a gap
      between the attitudes and practices of both physicians and nurses in
      communicating possible cancer risk to IVF clients. It would be beneficial to
      create a standardized risk communication protocol that would include information
      and guidelines for practice. More research must be conducted in this area, as
      there is almost no data on possible maternal risk from IVF treatment.

PMID- 24275208
TI  - Randomised controlled trial of a tailored information pack for patients
      undergoing surgery and treatment for rectal cancer.
AB  - PURPOSE: To evaluate the effects of a tailored information package for rectal
      cancer patients on satisfaction with information, anxiety and depression and
      readjustment. METHOD: The study used a randomised control trial method. Seventy
      six patients undergoing surgery and treatment for rectal cancer were randomly
      assigned to an intervention (n = 43) or control group (n = 33). The intervention
      group received an information pack tailored according to their treatment plan and
      preferred information. The control group received the information currently given
      to these patients. Satisfaction with information was measured using the Patient
      Satisfaction with Cancer Treatment Education (PSCaTE) scale, anxiety and
      depression were measured using the Hospital Anxiety and Depression Scale (HADS)
      and readjustment was measured using the Reintegration to Normal Living Index, at
      three time points. RESULTS: There was a statistically significant difference
      between the intervention and control group on pre and post intervention scores
      with patients in the intervention group expressing a higher level of satisfaction
      with information than those in the control group at Times 2 and 3 (p = 0.00 for
      both). The intervention group also had a significantly lower anxiety score than
      the control group at Time 3 (p = 0.03). There was no difference between
      depression and readjustment scores in the two groups. CONCLUSION: The results
      support the hypothesis that a tailored information pack for patients with rectal
      cancer will positively affect satisfaction with information. These results will
      enhance the knowledge base surrounding the provision of tailored information to
      specific patient groups.

PMID- 24275209
TI  - Review of attrition and adherence in exercise studies following hematopoietic
      stem cell transplantation.
AB  - PURPOSE: Implementing exercise programs in people receiving high-dose
      chemotherapy followed by bone marrow (BMT) or hematopoietic stem cell
      transplantation (SCT) presents unique challenges. This review examines subject
      attrition rates and reasons for attrition as well as adherence to exercise
      interventions following BMT/SCT. METHODS: Studies published between January 1985
      and December 2012 that prospectively tested an exercise intervention following
      BMT or SCT were included in the review. Evaluation criteria included: (1)
      exercise modality; (2) the amount of supervision required to implement the
      intervention; (3) timing of the intervention; (4) subject attrition rates and
      reasons for attrition; and (5) exercise adherence rates. RESULTS: Of the 20
      studies reviewed, most tested an aerobic exercise intervention or a combination
      of aerobic and strength training. Supervised exercise sessions were more commonly
      used than unsupervised sessions. The overall attrition rate was 18% for the 998
      subjects enrolled in the studies. Major reasons for attrition included death,
      change in health status, protocol issues, personal issues with subjects, and lost
      to follow-up/no reason provided. Authors of supervised exercise programs rarely
      published exercise adherence information. Unsupervised exercise programs relied
      mainly on self-report to document adherence. CONCLUSION: Exercise research
      following BMT/SCT is becoming more sophisticated as researchers build upon the
      expanding literature base. Questions regarding subject attrition and adherence to
      exercise interventions must be addressed to identify interventions that are
      likely to be successful when translated into clinical practice. Subject attrition
      from exercise studies following BMT/SCT is relatively low. Adherence information
      for exercise interventions needs to be regularly addressed.

PMID- 24275210
TI  - Change in rank of Megaperidae (Trematoda) to Megaperinae within the Apocreadiidae
      and description of Haintestinum amplum n. g., n. sp.
AB  - Haintestinum amplum n. g., n. sp. is described from the scrawled cowfish,
      Acanthostracion quadricornis, collected in the Eastern Gulf of Mexico off
      Florida, USA. The new species is relatively large and shares characters of the
      Apocreadiidae and Megaperidae but conforms to the diagnosis of neither. It
      belongs in a new genus possessing a pharynx with lobed anterior margin and
      intestine terminating in paired ani, like in megaperids, and, when compared with
      apocreadiids, it shares important anatomical features, including an I-shaped
      excretory vesicle, canicular seminal vesicle, eye-spot remnants, and
      pretesticular uterus and lacks a cirrus and cirrus sac. The H-shaped intestine
      and large funnel-shaped oral sucker without a U-shaped sphincter encircling half
      the anterior aperture are the most notable diagnostic characters of the new
      monotypic genus. Additionally, the phylogenetic position of the Megaperidae is
      investigated for the first time, using analysis of partial 28S rDNA gene
      sequences from H. amplum, two species in the Megapera, Thysanopharynx elongatus,
      and previously published 28S sequences of species from members of the
      Apocreadiata, Haploporoidae, Lepocreadiata, and Opisthorchiata. The resulting
      analysis demonstrated a close relationship among the new genus and the three
      species of megaperids, and the megaperids were most closely allied with
      Schistorchis zancli of the apocreadiids. Moreover, we now consider Megaperidae as
      the subfamily Megaperinae within the Apocreadiidae. 

PMID- 24275211
TI  - Unusual growth rate during cystic echinococcosis.
AB  - Cystic echinococcosis is a world wild zoonosis caused by Echinococcus granulosus,
      leading to hepatic and lung cysts with a usually slight growth rate. We report
      the case of an 82year-old Algerian woman with hepatic and lung cystic
      echinococcosis with a 10-fold size increase in 6months. 

PMID- 24275212
TI  - The role of tyrosine hydroxylase gene variants in suicide attempt in
      schizophrenia.
AB  - Evidence has shown that attempted suicide in psychiatric disorders is a complex
      interplay of genes and environment. Noradrenergic dysfunction due to
      abnormalities in the tyrosine hydroxylase (TH) gene has been implicated in the
      pathogenesis of suicidal behavior in mood disorders. However, suicide is a
      leading cause of mortality in schizophrenia too. Recent evidence suggests that TH
      gene variants may also increase the risk of suicide attempts in schizophrenia
      patients, although the interaction with established clinical risk factors is
      unclear. This study aimed to identify TH gene variants conferring risk for
      suicide attempt in schizophrenia while accounting for the interaction between
      this gene and clinical risk factors. We performed analysis on four TH SNPs
      (rs11564717, rs11042950, rs2070762, rs689) and the common TCAT repeat
      (UniSTS:240639) for 234 schizophrenia patients (51 suicide attempters and 183 non
      attempters). Clinical risk factors and ethnic stratification were included as
      covariates. Single marker analysis identified the SNP rs11564717 (p=0.042) and
      the TCAT(6) (p=0.004) as risk variants for suicide attempt. We also identified
      the haplotype A-A-A-G as a risk factor for suicide attempt (p=0.0025). In
      conclusion, our findings suggest that TH polymorphisms may contribute to the risk
      of attempted suicide in schizophrenia even after accounting for established
      clinical risk factors and ethnic stratification. Further larger scale studies are
      needed to confirm these findings and to understand the mechanisms underlying the
      role of TH gene variants in suicide attempt in schizophrenia. 

PMID- 24275213
TI  - Alterations in regional functional coherence within the sensory-motor network in
      amyotrophic lateral sclerosis.
AB  - Alteration of brain activity synchrony has been shown in amyotrophic lateral
      sclerosis (ALS) using seed-based functional connectivity analysis. However,
      regional activity synchrony has not been characterized in ALS. The purpose of
      this study was to assess regional brain synchrony by calculating regional data
      coherence of resting state functional MRI (rsfMRI), as well as its correlations
      to clinical indices. Twelve ALS patients and 12 age- and sex-matched healthy
      controls underwent rsfMRI scans. Coherence measurement was performed in the
      sensory-motor network (SMN), a key brain network impaired by ALS. Decreased
      coherence was found in the superior medial SMN, which was surrounded by increased
      coherence in the peripheral SMN areas. Decreased regional coherence in the right
      postcentral gyrus/precentral gyrus/superior frontal gyrus was correlated with
      high disease severity as indicated by lower ALSFRS-r scores; meanwhile, enhanced
      regional coherence in left postcentral gyrus and inferior parietal cortex was
      related to longer disease duration. Finally, increased coherence in left
      postcentral gyrus corresponds to fast disease progression rate. These ALS-related
      SMN regional coherence alterations suggest using regional coherence as a
      potential marker for studying ALS and its progression. 

PMID- 24275214
TI  - Clonal alteration of breast cancer receptors between primary ductal carcinoma in
      situ (DCIS) and corresponding local events.
AB  - BACKGROUND: Emerging data propose biomarker alteration due to clonal selection
      between the primary invasive breast cancer and corresponding metastases. In
      addition, impact on survival has been demonstrated. The present study
      investigates the relationship between the oestrogen receptor (ER), progesterone
      receptor (PR) and human epidermal growth factor receptor 2 (HER2) between primary
      ductal carcinoma in situ (DCIS) and intra-individually matched ipsilateral event.
      MATERIALS AND METHODS: The cohort includes 1504 patients, diagnosed with a
      primary DCIS between 1986 and 2004. Of the 274 patients who developed a local
      relapse, 135 developed a new in situ carcinoma and 139 an invasive cancer up to
      31st December 2011. ER and PR were identified by immunohistochemistry (IHC) and
      HER2 by silver-enhanced in situ hybridisation (SISH) as well as IHC. RESULTS: ER
      (n=112), PR (n=113) and HER2 (n=114) status from both the primary DCIS and the
      corresponding relapse were assessed and were demonstrated to be discordant in
      15.1%, 29.2% and 10.5% respectively. The receptor conversion was both from
      negative to positive and from positive to negative with no general pattern being
      seen in spite of sub-dividing into in situ relapse and invasive relapse. However,
      primary DCIS was HER2 positive in 40.3% whereas in situ and invasive relapses
      were HER2 positive in 42.9% and 34.5% respectively. CONCLUSIONS: Receptor
      conversion for ER, PR and HER2 status occurred between primary DCIS and
      corresponding local relapse in 10-30%. This study could not confirm that HER2
      overexpression in primary DCIS had any impact on tumour progression to invasive
      cancer which has been proposed.

PMID- 24275215
TI  - Treatment of late-onset hearing loss in infants with congenital cytomegalovirus
      infection.
AB  - OBJECTIVE: To evaluate the effect of antiviral treatment on late-onset hearing
      loss in infants with congenital cytomegalovirus infection. DESIGN: The database
      of all infants who had normal hearing at birth, and treated for late-onset
      hearing loss was collected. The primary study endpoint was the need for a
      cochlear implant at the last follow-up visit. RESULTS: Twenty-one infants met the
      inclusion criteria. Brain stem-evoked response audiometry testing revealed
      hearing loss in 35 of 42 ears (83%). Mean age at diagnosis of hearing loss was
      7.4 +/- 3.7 months and onset of antiviral therapy 10.3 +/- 7.8 months. None of
      the ears showed further deterioration as referred to pretreatment values. Hearing
      thresholds improved in 29 ears (69%). None of the patients needed a cochlear
      implant. CONCLUSIONS: In children with late-onset hearing loss due to
      cytomegalovirus infection, antiviral treatment appears to prevent further
      deterioration and produce improvement. Controlled studies are needed to verify
      this observation.

PMID- 24275216
TI  - Adolescents with cerebral palsy: transitioning to adult health care services.
AB  - Data from the 2009-2010 US National Survey of Children with Special Health Care
      Needs were examined to determine the health, developmental and behavioral status
      of adolescents with cerebral palsy (CP) and to assess how well pediatric health
      care providers were preparing them for transition to adult health care services.
      Adolescents with CP had no higher rates of attention deficit hyperactivity
      disorder, depression, anxiety, oppositional or conduct disorders, or autism
      spectrum than a comparison group. However, those with CP participated less in
      sports, clubs, or other organized activities (P < .001). Neither group reported
      much help in coordinating health services or preparing for transition to adult
      health care services. Inadequate adult health care services have a direct and
      unsatisfactory impact on the adult life span. Physicians and other health care
      providers who include adolescents with CP in their practices should begin
      discussion and planning for transition to adult health care early in adolescence.

PMID- 24275217
TI  - The OPPERA study: act two.

PMID- 24275218
TI  - Multivariable modeling of phenotypic risk factors for first-onset TMD: the OPPERA
      prospective cohort study.
AB  - Incidence of temporomandibular disorder (TMD) was predicted with multivariable
      models that used putative risk factors collected from initially TMD-free
      individuals in the Orofacial Pain: Prospective Evaluation and Risk Assessment
      (OPPERA) study. The 202 baseline risk factors included sociodemographic and
      clinical characteristics, measures of general health status, experimental pain
      sensitivity, autonomic function, and psychological distress. Study participants
      (n = 2,737) were then followed prospectively for a median of 2.8 years to
      ascertain cases of first-onset TMD. Lasso regression and random forest models
      were used to predict incidence of first-onset TMD using all of the aforementioned
      measures. Variable importance scores identified the most important risk factors,
      and their relationship with TMD incidence was illustrated graphically using
      partial dependence plots. Two of the most important risk factors for elevated TMD
      incidence were greater numbers of comorbid pain conditions and greater extent of
      nonspecific orofacial symptoms. Other important baseline risk factors were
      preexisting bodily pain, heightened somatic awareness, and greater extent of pain
      in response to examiners' palpation of the head, neck, and body. Several
      demographic variables persisted as risk factors even after adjusting for other
      OPPERA variables, suggesting that environmental variables not measured in OPPERA
      may also contribute to first-onset TMD. PERSPECTIVE: Multivariable methods were
      used to identify the most important predictors of first-onset TMD in the OPPERA
      study. Important variables included comorbid pain conditions, preexisting pain,
      and somatic awareness. Demographic characteristics, which probably reflect
      environmental variables not measured in OPPERA, also appear to play an important
      role in the etiology of TMD.

PMID- 24275219
TI  - Summary of findings from the OPPERA prospective cohort study of incidence of
      first-onset temporomandibular disorder: implications and future directions.
AB  - Papers in this issue investigate when and how putative risk factors influence
      development of first-onset, painful temporomandibular disorder (TMD). The results
      represent first findings from the Orofacial Pain: Prospective Evaluation and Risk
      Assessment (OPPERA) prospective cohort study that monitored 2,737 men and women
      aged 18 to 44 years recruited at 4 U.S. study sites. During a median 2.8-year
      follow-up period, 260 participants developed TMD. The average incidence rate of
      4% per annum was influenced by a broad range of phenotypic risk factors including
      sociodemographic characteristics, health status, clinical orofacial factors,
      psychological functioning, pain sensitivity, and cardiac autonomic responses. A
      novel method of multivariable analysis used random forest models to
      simultaneously evaluate contributions of all 202 phenotypic variables. Variables
      from the health status domain made the greatest contribution to TMD incidence,
      followed closely by psychological and clinical orofacial domains. However, only a
      few measures of pain sensitivity and autonomic function contributed to TMD
      incidence, and their effects were modest. Meanwhile, age and study site were
      independent predictors of TMD incidence, even after controlling for other
      phenotypes. Separate analysis of 358 genes that regulate pain found several novel
      genetic associations with intermediate phenotypes that, themselves, are risk
      factors for TMD, suggesting new avenues to investigate biological pathways
      contributing to TMD. PERSPECTIVE: Collectively, the papers in this issue
      demonstrate that TMD is a complex disorder with multiple causes consistent with a
      biopsychosocial model of illness. It is a misnomer and no longer appropriate to
      regard TMD solely as a localized orofacial pain condition.

PMID- 24275220
TI  - Study protocol, sample characteristics, and loss to follow-up: the OPPERA
      prospective cohort study.
AB  - When studying incidence of pain conditions such as temporomandibular disorder
      (TMD), repeated monitoring is needed in prospective cohort studies. However,
      monitoring methods usually have limitations and, over a period of years, some
      loss to follow-up is inevitable. The OPPERA prospective cohort study of first
      onset TMD screened for symptoms using quarterly questionnaires and examined
      symptomatic participants to definitively ascertain TMD incidence. During the
      median 2.8-year observation period, 16% of the 3,263 enrollees completed no
      follow-up questionnaires, others provided incomplete follow-up, and examinations
      were not conducted for one third of symptomatic episodes. Although screening
      methods and examinations were found to have excellent reliability and validity,
      they were not perfect. Loss to follow-up varied according to some putative TMD
      risk factors, although multiple imputation to correct the problem suggested that
      bias was minimal. A second method of multiple imputation that evaluated bias
      associated with omitted and dubious examinations revealed a slight underestimate
      of incidence and some small biases in hazard ratios used to quantify effects of
      risk factors. Although "bottom line" statistical conclusions were not affected,
      multiply-imputed estimates should be considered when evaluating the large number
      of risk factors under investigation in the OPPERA study. PERSPECTIVE: These
      findings support the validity of the OPPERA prospective cohort study for the
      purpose of investigating the etiology of first-onset TMD, providing the
      foundation for other papers investigating risk factors hypothesized in the OPPERA
      project.

PMID- 24275221
TI  - Signs and symptoms of first-onset TMD and sociodemographic predictors of its
      development: the OPPERA prospective cohort study.
AB  - Although cross-sectional studies of temporomandibular disorder (TMD) often report
      elevated prevalence in young women, they do not address the risk of its
      development. Here we evaluate sociodemographic predictors of TMD incidence in a
      community-based prospective cohort study of U.S. adults. Symptoms and pain
      related disability in TMD cases are also described. People aged 18 to 44 years
      with no history of TMD were enrolled at 4 study sites when they completed
      questionnaires about sociodemographic characteristics. During the median 2.8-year
      follow-up period, 2,737 participants completed quarterly screening
      questionnaires. Those reporting symptoms were examined clinically and 260 had
      first-onset TMD. Additional questionnaires asked about severity and impact of
      their symptoms. Univariate and multivariable Cox regression models quantified
      associations between sociodemographic characteristics and TMD incidence. First
      onset TMD developed in 3.9% of participants per annum, typically producing mild
      to moderate levels of pain and disability in cases. TMD incidence was positively
      associated with age, whereas females had only slightly greater incidence than
      males. Compared to whites, Asians had lower TMD incidence whereas African
      Americans had greater incidence, although the latter was attenuated somewhat
      after adjusting for satisfaction with socioeconomic circumstances. PERSPECTIVE:
      In this study of 18- to 44-year-olds, TMD developed at a higher rate than
      reported previously for similar age groups. TMD incidence was positively
      associated with age but weakly associated with gender, thereby differing from
      demographic patterns of prevalence found in some cross-sectional studies.
      Experiences related to aging merit investigation as etiologic influences on
      development of TMD.

PMID- 24275222
TI  - Clinical orofacial characteristics associated with risk of first-onset TMD: the
      OPPERA prospective cohort study.
AB  - Case-control studies have documented clinical manifestations of chronic
      temporomandibular disorder (TMD), whereas clinical predictors of TMD development
      are largely unknown. We evaluated 41 clinical orofacial characteristics thought
      to predict first-onset TMD in a prospective cohort study of U.S. adults aged 18
      to 44 years. During the median 2.8-year follow-up period, 2,737 people completed
      quarterly screening questionnaires. Those reporting symptoms were examined and
      260 people were identified with first-onset TMD. Univariate and multivariable Cox
      regression models quantified associations between baseline clinical orofacial
      measures and TMD incidence. Significant predictors from baseline self-report
      instruments included oral parafunctions, prior facial pain and its life-impact,
      temporomandibular joint noises and jaw locking, and nonspecific orofacial
      symptoms. Significant predictors from the baseline clinical examination were pain
      on jaw opening and pain from palpation of masticatory, neck, and body muscles.
      Examiner assessments of temporomandibular joint noise and tooth wear facets did
      not predict incidence. In multivariable analysis, nonspecific orofacial symptoms,
      pain from jaw opening, and oral parafunctions predicted TMD incidence. The
      results indicate that only a few orofacial examination findings influenced TMD
      incidence, and only to a modest degree. More pronounced influences were found for
      self-reported symptoms, particularly those that appeared to reflect alterations
      to systems beyond the masticatory tissues. PERSPECTIVE: OPPERA's prospective
      cohort study identifies predictors of first-onset TMD comprising self-reported
      orofacial symptoms and examination findings. The results suggest a complex
      pattern of TMD etiology that is influenced by disorders locally, in masticatory
      tissues, and systemically, in pain-regulatory systems.

PMID- 24275223
TI  - General health status and incidence of first-onset temporomandibular disorder:
      the OPPERA prospective cohort study.
AB  - Temporomandibular disorder (TMD) overlaps with other health conditions, but no
      study has examined which of these conditions increase the risk of developing
      first-onset TMD. The authors prospectively evaluated the relationship between
      health status at enrollment and subsequent incidence of TMD in 2,722 men and
      women. Participants aged 18 to 44 years had no history of TMD and were clinically
      free of TMD when enrolled in 2006 to 2008 at 4 U.S. study sites in the Orofacial
      Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort
      study. First-onset examiner-classified TMD developed in 260 people over a median
      2.8 years of follow-up. Cox regression estimated the association between health
      conditions and TMD incidence while accounting for potential confounders.
      Incidence of first-onset TMD was 50% higher for people with low back pain
      (adjusted hazard ratio [AHR] = 1.50, 95% confidence limits [CLs]: 1.08, 2.10) and
      75% higher for people with genital pain symptoms (AHR = 1.75, 95% CLs = 1.04,
      2.93) than people without a history of these pain disorders. Digit ratio, a
      marker of intrauterine exposure to sex hormones, was significantly associated
      with TMD incidence. Other independent predictors of first-onset TMD were sleep
      disturbance and cigarette smoking. These findings reveal multiple influences of
      health status on incidence of first-onset TMD. PERSPECTIVE: This article examines
      health conditions that commonly overlap with TMD to determine which ones predict
      first-onset TMD. A history of low back pain and genital pain conditions at
      baseline were important predictors. Novel findings were that disrupted sleep and
      conditions in utero may increase incidence of first-onset TMD.

PMID- 24275224
TI  - Pain sensitivity and autonomic factors associated with development of TMD: the
      OPPERA prospective cohort study.
AB  - Multiple studies report that individuals with chronic temporomandibular disorder
      (TMD) have enhanced sensitivity to experimental pain. Additionally, chronic TMD
      cases show altered autonomic function, including elevated heart rate and reduced
      heart rate variability. However, causal inferences regarding the association
      between TMD and pain sensitivity and autonomic function cannot be drawn from
      these cross-sectional observations. The prospective Orofacial Pain: Prospective
      Evaluation and Risk Assessment (OPPERA) study examines whether measures of pain
      sensitivity or cardiac autonomic function provide predictive value in TMD
      incidence. A cohort of 2,737 initially TMD-free participants was followed for up
      to 5.2 years, during which time 260 developed first-onset TMD. Fourteen of 39
      experimental pain measures produced significant hazard ratios, such that greater
      pain sensitivity was associated with greater TMD incidence. A single autonomic
      measure-heart rate at rest-was also associated significantly with greater TMD
      incidence. In contrast, using the same measures of pain sensitivity and cardiac
      autonomic function, we previously reported a larger group of variables that was
      significantly associated with chronic TMD in the OPPERA case-control study.
      Future studies should investigate whether premorbid pain sensitivity or autonomic
      function more specifically predicts risk of developing chronic TMD than first
      onset TMD. PERSPECTIVE: Our previous case-control studies showed that
      associations with both pain sensitivity and cardiac autonomic function are
      profound in chronic TMD cases. Here we show that some measures of enhanced pain
      sensitivity contribute modestly to the risk of developing TMD whereas autonomic
      dysregulation appears to confer little or no risk for TMD incidence.

PMID- 24275227
TI  - Diagnosis of diabetes mellitus or cardiovascular disease and lifestyle changes -
      the Doetinchem cohort study.
AB  - OBJECTIVE: To study whether being diagnosed with a cardiovascular disease (CVD)
      or diabetes mellitus (DM) is associated with improvements in lifestyles. METHODS:
      We used data from the Doetinchem Cohort Study, a prospective study among 6386
      Dutch men and women initially aged 20-59years who were examined four times over
      15years (1987-2007). Logistic and linear regression models were used to assess
      the effect of a self-reported diagnosis of CVD (n=403) or DM (n=221) on smoking,
      alcohol consumption, weight, diet and physical activity. RESULTS: Self-reported
      diagnosis of CVD increased rates of smoking cessation (OR=2.2, 95%CI 1.6 - 3.1).
      Adults reporting a diagnosis of DM (relatively) decreased weight (3.2%, 95%CI 2.2
      - 4.2), (relatively) decreased energy intake (4.2%, 95%CI 0.7 - 7.7), decreased
      energy percentage from saturated fat (0.4%, 95%CI 0.0 - 0.9) and increased fish
      consumption (2.8 g/day, 95%CI 0.4 - 5.1). A self-reported diagnosis of CVD or DM
      was not associated with changes in physical activity. CONCLUSION: A diagnosis of
      CVD or DM may act, along with possible effects of medical treatment, as a trigger
      to adopt a healthier lifestyle in terms of smoking cessation, healthier diet and
      weight loss.

PMID- 24275225
TI  - Psychological factors associated with development of TMD: the OPPERA prospective
      cohort study.
AB  - Case-control studies have consistently associated psychological factors with
      chronic pain in general and with temporomandibular disorder (TMD) specifically.
      However, only a handful of prospective studies have explored whether preexisting
      psychological characteristics represent risk factors for first-onset TMD. The
      current findings derive from the prospective cohort study of the Orofacial Pain:
      Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For
      this study, 3,263 TMD-free participants completed a battery of psychological
      instruments assessing general psychological adjustment and personality, affective
      distress, psychosocial stress, somatic symptoms, and pain coping and
      catastrophizing. Study participants were then followed prospectively for an
      average of 2.8 years to ascertain cases of first-onset of TMD, and 2,737 provided
      follow-up data and were considered in the analyses of TMD onset. In bivariate and
      demographically adjusted analyses, several psychological variables predicted
      increased risk of first-onset TMD, including reported somatic symptoms,
      psychosocial stress, and affective distress. Principal component analysis of 26
      psychological scores was used to identify latent constructs, revealing 4
      components: stress and negative affectivity, global psychological and somatic
      symptoms, passive pain coping, and active pain coping. In multivariable analyses,
      global psychological and somatic symptoms emerged as the most robust risk factor
      for incident TMD. These findings provide evidence that measures of psychological
      functioning can predict first onset of TMD. Future analyses in the OPPERA cohort
      will determine whether these psychological factors interact with other variables
      to increase risk for TMD onset and persistence. PERSPECTIVE: This article reports
      that several premorbid psychological variables predict first-onset TMD in the
      OPPERA study, a large prospective cohort study designed to discover causal
      determinants of TMD pain. Measures of somatic symptoms were most strongly
      associated with TMD onset, but perceived stress, previous life events, and
      negative affect also predicted TMD incidence.

PMID- 24275226
TI  - Genetic variants associated with development of TMD and its intermediate
      phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort
      study.
AB  - Genetic risk factors are believed to combine with environmental exposures and
      contribute to the risk of developing temporomandibular disorder (TMD). In this
      prospective cohort study, 2,737 people without TMD were assessed for common
      genetic variation in 358 genes known to contribute to nociceptive pathways,
      inflammation, and affective distress. During a median follow-up period of 2.8
      years, 260 people developed first-onset TMD. Hazard ratios were computed as
      measures of association between 2,924 single-nucleotide polymorphisms and TMD
      incidence. After correction for multiple testing, no single single-nucleotide
      polymorphism was significantly associated with risk of onset TMD. However,
      several single-nucleotide polymorphisms exceeded Bonferroni correction for
      multiple comparison or false discovery rate thresholds (.05, .1, or .2) for
      association with intermediate phenotypes shown to be predictive of TMD onset.
      Nonspecific orofacial symptoms were associated with voltage-gated sodium channel,
      type I, alpha subunit (SCN1A, rs6432860, P = 2.77 * 10(-5)) and angiotensin I
      converting enzyme 2 (ACE2, rs1514280, P = 4.86 * 10(-5)); global psychological
      symptoms with prostaglandin-endoperoxide synthase 1 (PTGS1, rs3842803, P = 2.79 *
      10(-6)); stress and negative affectivity with amyloid-beta (A4) precursor protein
      (APP, rs466448, P = 4.29 * 10(-5)); and heat pain temporal summation with
      multiple PDZ domain protein (MPDZ, rs10809907, P = 3.05 * 10(-5)). The use of
      intermediate phenotypes for complex pain diseases revealed new genetic pathways
      influencing risk of TMD. PERSPECTIVE: This article reports the findings of a
      large candidate gene association study of first-onset TMD and related
      intermediate phenotypes in the OPPERA Study. Although no genetic markers
      predicted TMD onset, several genetic risk factors for clinical, psychological,
      and sensory phenotypes associated with TMD onset were observed.

PMID- 24275228
TI  - Wastewater analysis reveals regional variability in exposure to abused drugs and
      opioids in Finland.
AB  - Abused drug concentrations were determined in nine Finnish wastewater treatment
      plants (WWTPs), representing the metropolitan area, university cities and rural
      towns. In an eight-day study period in August 2012, 24-hour composite influent
      wastewater samples were collected. Biological markers and census-based
      information were used to estimate the size of the population served. The
      analytical method included solid phase extraction, liquid chromatographic
      separation, tandem mass spectrometric identification, and quantification using
      isotope-labeled internal standards. The study covered amphetamines, cannabis and
      cocaine. The levels of some opioids used in treatment and their metabolites were
      also determined. Amphetamine was the most prevalent drug of abuse, the median
      loads varying between the cities from 4.16 to 29.6 mg/1000 inhabitants/d. In
      three western cities methamphetamine was detected in even higher amounts, ranging
      from 0.87 to 47.5mg/1000 inhabitants/d. Ecstasy (MDMA) and cocaine (as
      benzoylecgonine, BE) were found in higher concentrations during weekends compared
      to weekdays, the difference being statistically significant. The concentration of
      tetrahydrocannabinol-9-carboxylic acid (THCA) was below the limit of
      quantification in the two rural towns, while in the other cities the load varied
      between 3.77 and 20.7 mg/1000 inhabitants/d. The average variation in BE load was
      0.05-6.82 and that of MDMA 0-20.6 mg/1000 inhabitants/d. While the metropolitan
      area showed the highest loads of abused drugs, the substances were continuously
      detected at all WWTPs included in the study. The median concentration of codeine
      ranged from 164 to 325 mg/1000 inhabitants/d and that of morphine from 18.8 to
      31.5mg/1000 inhabitants/d. The methadone load was below the level of detection in
      two towns, and at the other locations were 1.22-9.46 mg/1000 inhabitants/d. The
      first metabolite of heroin, 6-monoacetylmorphine (6-MAM), was not detected at
      all. Although the method has limitations, wastewater analysis gives additional
      information for assessing the degree of drug abuse and range of drugs abused in a
      society.

PMID- 24275229
TI  - Modulation of transient receptor vanilloid 1 activity by transient receptor
      potential ankyrin 1.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a nonselective ligand-gated
      cation channel responding to noxious heat, protons, and chemicals such as
      capsaicin. TRPV1 is expressed in sensory neurons and plays a critical role in
      pain associated with tissue injury, inflammation, and nerve lesions. Transient
      receptor potential ankyrin 1 (TRPA1) is coexpressed with TRPV1. It is activated
      by compounds that cause a burning sensation (e.g., mustard oil) and, indirectly,
      by components of the inflammatory milieu eliciting nociceptor excitation and pain
      hypersensitivity. Previous studies indicate an interaction of TRPV1 and TRPA1
      signaling pathways. Here we sought to examine the molecular mechanisms underlying
      such interactions in nociceptive neurons. We first excluded physical interactions
      of both channels using radioligand binding studies. By microfluorimetry,
      electrophysiological experiments, cAMP measurements, and site-directed
      mutagenesis we found a sensitization of TRPV1 after TRPA1 stimulation with
      mustard oil in a calcium and cAMP/protein kinase A (PKA)-dependent manner. TRPA1
      stimulation enhanced TRPV1 phosphorylation via the putative PKA phosphorylation
      site serine 116. We also detected calcium-sensitive increased TRPV1 activity
      after TRPA1 activation in dorsal root ganglion neurons. The inhibition of TRPA1
      by HC-030031 (1,2,3,6-tetrahydro-1,3-dimethyl-N-[4-(1-methylethyl)phenyl]-2,6
      dioxo-7H-purine-7-acetamide, 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H
      purin-7-yl)-N-(4-isopropylphenyl)acetamide) after its initial stimulation (and
      the calcium-insensitive TRPA1 mutant D477A) still showed increased capsaicin
      induced TRPV1 activity. This excludes a calcium-induced additive TRPA1 current
      after TRPV1 stimulation. Our study shows sensitization of TRPV1 via activation of
      TRPA1, which involves adenylyl cyclase, increased cAMP, subsequent translocation
      and activation of PKA, and phosphorylation of TRPV1 at PKA phosphorylation
      residues. This suggests that cross-sensitization of TRP channels contributes to
      enhanced pain sensitivity in inflamed tissues. 

PMID- 24275230
TI  - Glutamate, substance P, and calcitonin gene-related peptide cooperate in
      inflammation-induced heat hyperalgesia.
AB  - The transient receptor potential cation channel subfamily V member 1 (TRPV1) is
      known as a thermosensor and integrator of inflammation-induced hyperalgesia.
      TRPV1 is expressed in a subpopulation of primary afferent neurons that express
      several different neurotransmitters. The role of the TRPV1 channel in the
      development of hyperalgesia is established, but the role of the neurotransmitter
      glutamate, used partially by the same neuronal population and thus probably
      mediating the response, is still under investigation. We have used a Trpv1-Cre
      mouse line in which we either ablated Trpv1-Cre expressing neurons or induced
      vesicular glutamate transporter 2 (Vglut2) deficiency in Trpv1-Cre expressing
      neurons and investigated specific states of hyperalgesia after persistent
      inflammation. Furthermore, by pharmacologic inhibition of substance P (SP) or
      calcitonin gene-related peptide (CGRP) signaling in Vglut2-deficient mice, we
      also evaluated the contribution of SP or CGRP to inflammation-induced
      hyperalgesia, with or without the presence of vesicular glutamate transporter 2
      (VGLUT2)-mediated glutamatergic transmission in Trpv1-Cre neurons. This
      examination, together with c-Fos analyses, showed that VGLUT2-mediated
      glutamatergic transmission in Trpv1-Cre afferents together with SP or CGRP is
      essential for the development of the heat hyperalgesia associated with persistent
      inflammation. Additionally, SP-, CGRP-, and VGLUT2-mediated transmission together
      were found to play a role in the development of mechanical hyperalgesia after
      persistent inflammation. 

PMID- 24275231
TI  - Trends in maternal mortality in Hungary between 1978 and 2010.
AB  - OBJECTIVE: We evaluated the trends of the last decades in maternal mortality in
      Hungary and compared Hungarian results with those of other European countries.
      STUDY DESIGN: Cases of maternal death in Hungary during the study period from
      calendar year 1978 to 2010 were analyzed in a retrospective manner to
      characterize mortality distribution and to identify potential clinical or
      demographic predictors. Data in all cases were extracted both from the national
      Obstetric Registry operated by the National Institute of Gynecology and
      Obstetrics, from the Hungarian Central Bureau of Statistics and from the National
      Public Health and Medical Officer Service. Detailed clinical data were obtained
      based on obligatory reporting by individual clinical institutions. RESULTS: The
      annual maternal mortality rate (MMR) was 26.7 per 100,000 live births in the
      period 1978-1987 and declined significantly to 10.9 per 100,000 live births in
      the period 1997-2010. In the period 1988-1996 (with missing associated clinical
      and demographic data) the MMR was 16.4 per 100,000 live births. The proportion of
      delivery-associated causes of death increased significantly between the two study
      periods from 49.4% to 62.9% (p<0.05). Among obstetric causes of death, the rate
      of thromboembolism showed a significant increase, while there was a trend toward
      a decline in rate of maternal deaths attributable to hemorrhagic shock. Among
      medical causes of death not directly attributable to obstetric complications, the
      rate of renal and gastrointestinal etiologies declined significantly throughout
      the study periods. CONCLUSIONS: We observed a marked decline in maternal
      mortality during the last few decades in Hungary. Recent changes in mortality
      distribution highlight current characteristics of pregnancy care in Hungary and
      may help identify strategies for future improvement.

PMID- 24275232
TI  - Maximum standardized lymph node uptake value could be an important predictor of
      recurrence and survival in patients with cervical cancer.
AB  - OBJECTIVES: To investigate prognostic values of maximum standardized lymph node
      (LN) uptake (SUVmax), minimum apparent LN diffusion coefficient (ADCmin), and LN
      short-axis length in women with cervical cancer. STUDY DESIGN: Retrospective
      review of diffusion-weighted magnetic resonance imaging (DWI) and positron
      emission tomography/computed tomography (PET/CT) of LN confined to the pelvis in
      80 cervical cancer patients before undergoing radiotherapy (RT) with or without
      concurrent chemotherapy. Optimal cut-off values for disease-free survival (DFS)
      and overall survival (OS) were determined by receiver operating characteristic
      (ROC) curve analysis. We used ROC curve analyses to evaluate whether LN SUVmax,
      LN ADCmin and LN short-axis length predicted risk of recurrence or survival.
      RESULTS: Median DFS and OS for all patients were 18.97 and 22.28 months,
      respectively. DFS and OS rates of patients with high LN SUVmax was significantly
      lower than those of patients exhibiting low LN SUVmax (P=0.003 and P=0.019).
      Patients with low LN ADCmin had poorer DFS and OS than those with high LN ADCmin
      (P=0.033 and P=0.005). DFS for patients exhibiting longer LN short-axis length
      was significantly lower than those of patients exhibiting shorter LN short-axis
      length (P=0.018). Multivariate analyses indicated that high LN SUVmax was an
      independent predictor for both DFS and OS (P=0.0231 and P=0.0146). CONCLUSIONS:
      LN SUVmax could be an important predictor of recurrence and survival in patients
      with cervical cancer confined to the pelvis.

PMID- 24275233
TI  - Sharp compared with blunt fascial incision at cesarean delivery: a randomized
      controlled trial with each case as her own control.
AB  - OBJECTIVE: To compare patient preference for either sharp incision with scissors
      or blunt manual cleavage of the fascia at cesarean delivery in a randomized
      controlled trial in which each woman was her own control. STUDY DESIGN: Women
      undergoing primary cesarean delivery (n=34) were randomized to side distribution
      of sharp or blunt incision of the fascia (sharp right and blunt left or blunt
      right and sharp left) and followed three months postoperatively. The primary
      outcome was patient preference for the right or left side of the scar 3 months
      postoperatively and modeled by polytomous logistic regression. The secondary
      outcome was difference in pain between the two sides measured on a 0.0-10.0
      numerical rating scale at 1, 3, and 7 days and 1 and 3 months postoperatively.
      Pain scores were analyzed with a Wilcoxon signed rank test. RESULTS: 28 cases
      were analyzed and no significant difference was found in preference after three
      months. Nine women preferred the sharp (32%, 95% CI 16-52%) and 7 the blunt side
      (25%, 95% CI 11-45%) (P=0.804). Pain scores did not differ significantly between
      the two sides at any time postoperatively either at rest or during mobilization.
      CONCLUSION: No significant difference was found in patient preference with regard
      to sharp or blunt incision of the fascia, nor was there a significant difference
      in postoperative pain scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov:
      www.clinicaltrials.org;NCT01297725.

PMID- 24275234
TI  - Is it possible to simplify risk stratification scores for patients with ST
      segment elevation myocardial infarction undergoing primary angioplasty?
AB  - INTRODUCTION: There are several risk scores for stratification of patients with
      ST-segment elevation myocardial infarction (STEMI), the most widely used of which
      are the TIMI and GRACE scores. However, these are complex and require several
      variables. The aim of this study was to obtain a reduced model with fewer
      variables and similar predictive and discriminative ability. METHODS: We studied
      607 patients (age 62 years, SD=13; 76% male) who were admitted with STEMI and
      underwent successful primary angioplasty. Our endpoints were all-cause in
      hospital and 30-day mortality. Considering all variables from the TIMI and GRACE
      risk scores, multivariate logistic regression models were fitted to the data to
      identify the variables that best predicted death. RESULTS: Compared to the TIMI
      score, the GRACE score had better predictive and discriminative performance for
      in-hospital mortality, with similar results for 30-day mortality. After data
      modeling, the variables with highest predictive ability were age, serum
      creatinine, heart failure and the occurrence of cardiac arrest. The new
      predictive model was compared with the GRACE risk score, after internal
      validation using 10-fold cross validation. A similar discriminative performance
      was obtained and some improvement was achieved in estimates of probabilities of
      death (increased for patients who died and decreased for those who did not).
      CONCLUSION: It is possible to simplify risk stratification scores for STEMI and
      primary angioplasty using only four variables (age, serum creatinine, heart
      failure and cardiac arrest). This simplified model maintained a good predictive
      and discriminative performance for short-term mortality.

PMID- 24275235
TI  - Double duct sign in a 3-year-old child.

PMID- 24275236
TI  - Potential benefit of telbivudine on renal function does not outweigh its high
      rate of antiviral drug resistance and other adverse effects.

PMID- 24275238
TI  - New insights into the cell lineage of pancreatic ductal adenocarcinoma: evidence
      for tumor stem cells in premalignant lesions?

PMID- 24275239
TI  - A rare finding on evaluation for iron deficiency anemia.

PMID- 24275240
TI  - Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten
      sensitivity.

PMID- 24275241
TI  - Diet as a therapy for irritable bowel syndrome: progress at last.

PMID- 24275243
TI  - Endoscopy-related factors contributing to postcolonoscopy colorectal cancers.

PMID- 24275244
TI  - Detection of autoantibodies to periplakin and envoplakin in paraneoplastic
      pemphigus but not idiopathic pulmonary fibrosis using full-length recombinant
      proteins.
AB  - BACKGROUND: Paraneoplastic pemphigus (PNP) serum preferentially reacts with
      periplakin and envoplakin, which are plakin family proteins localized to
      desmosomes and intermediate filaments. Recently, anti-periplakin antibodies were
      also detected in patients with idiopathic pulmonary fibrosis (IPF). Although
      previous epitope-mapping studies showed multiple epitopes in each protein, enzyme
      linked immunosorbent assays have used several truncated, but not full-length,
      recombinant proteins. METHODS: This study aimed to produce full-length
      biotinylated recombinant proteins of periplakin and envoplakin for detection of
      autoantibodies by immunoprecipitation and ELISA. Serum from a PNP patient who had
      been confirmed as carrying anti-periplakin and anti-envoplakin antibodies in our
      previous study was used as a positive control. Sera from 15 patients with IPF
      were analyzed for both antibodies by immunoprecipitation and by ELISA. RESULTS:
      The PNP serum reacted strongly with the full-length recombinant proteins in
      immunoprecipitation and ELISA. Longitudinal serum samples from the PNP patient
      showed a clear decline of autoantibodies to both periplakin and envoplakin. None
      of the IPF sera showed both autoantibodies. CONCLUSIONS: We found that the
      detection of anti-periplakin and anti-envoplakin antibodies using full-length
      recombinant proteins is useful immunoprecipitation and ELISA.

PMID- 24275245
TI  - Stabilities of intact hemoglobin molecules and hemoglobin peptides in dried blood
      samples.

PMID- 24275246
TI  - A study of transport suppression in an undoped AlGaAs/GaAs quantum dot single
      electron transistor.
AB  - We report a study of transport blockade features in a quantum dot single-electron
      transistor, based on an undoped AlGaAs/GaAs heterostructure. We observe
      suppression of transport through the ground state of the dot, as well as negative
      differential conductance at finite source-drain bias. The temperature and
      magnetic field dependences of these features indicate the couplings between the
      leads and the quantum dot states are suppressed. We attribute this to two
      possible mechanisms: spin effects which determine whether a particular charge
      transition is allowed based on the change in total spin, and the interference
      effects which arise from coherent tunnelling of electrons in the quantum dot. 

PMID- 24275247
TI  - Density of states of helically symmetric boron carbon nitride nanotubes.
AB  - Motivated by the existence of helical wrapping patterns in composite nanotube
      systems, in this work we study the effects of the helical incorporation of carbon
      atoms in boron nitride nanotubes. We consider the substitutional carbon atoms
      distributed in stripes forming helical patterns along the nanotube axis. The
      density of states and energy band gap were calculated adopting Green function
      formalism by using the Rubio-Sancho technique in order to solve the matrix Dyson
      equation. We report the effects of the helical atomic distribution of carbon
      atoms on the behaviour of the density of states and the energy band gap. In
      particular, we show that the electronic energy band gap displays a non
      monotonical dependence on the helical pattern, oscillating as a function of the
      helical angle theta. 

PMID- 24275248
TI  - Synthesis and biological evaluation of new epalrestat analogues as aldose
      reductase inhibitors (ARIs).
AB  - Baylis-Hillman chemistry derived four series of new epalrestat analogues were
      synthesized. Three structural changes are introduced in these 39 new epalrestat
      analogues synthesized. All compounds were evaluated for their in vitro aldose
      reductase inhibitory (ALR) activity. Biological activity data indicates that
      compounds 6, 16, 19, 28 and 29 are potent and the activity is in the range of
      reference drug, epalrestat. Molecular modelling studies were performed to
      understand the binding interactions of these active molecules with the ALR
      protein. Molecular docking data indicates the key interactions of epalrestat were
      retained in some of the active compounds whereas some new interactions were
      noticed for other molecules. The modifications introduced on epalrestat have
      impact for developing a new-type of ALR inhibitor.

PMID- 24275249
TI  - Functionalized curcumin analogs as potent modulators of the Wnt/beta-catenin
      signaling pathway.
AB  - Osteosarcoma is a primary bone malignancy with aggressive metastatic potential
      and poor prognosis rates. In our earlier work we have investigated the
      therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by
      its ability to regulate the Wnt/beta-catenin signaling pathway. However, the
      clinical use of curcumin is limited owing to its low potency and poor
      pharmacokinetic profile. In this study, an attempt was made to achieve more
      potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic
      chemical modifications of curcumin. We synthesized a total of five series
      consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of
      beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to
      60-fold more potent than curcumin in inhibiting Wnt activity, were further
      assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western
      blot analysis showed disruption of beta-catenin protein nuclear translocation
      following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also
      found that these compounds were more potent than 1a (curcumin) in impeding the
      invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity.
      Structure-activity-relationship studies revealed that Wnt inhibitory effects
      could be enhanced by shortening and restraining the flexibility of the 7-carbon
      linker moiety connecting the terminal aromatic rings of curcumin and substituting
      both rings with appropriate substituents. Our results demonstrate that the
      synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell
      lines as compared to parental curcumin and are good lead compounds for further
      development. Future in vivo tests with these compounds will define their
      therapeutic potentials as promising drug candidates for clinical treatment of
      osteosarcoma. 

PMID- 24275250
TI  - Sternites and spiracles - the unclear homology of ventral sclerites in the basal
      millipede order Glomeridesmida (Myriapoda, Diplopoda).
AB  - We report the discovery of a ventral plate in the basal and little-known
      chilognath millipede order Glomeridesmida. This ventral plate, interpreted here
      as a 'true sternite', is clearly separate from both the coxa and the more lateral
      stigma-carrying plates commonly referred to as 'diplopod sternites'. Therefore,
      the lateral, stigma-carrying plates of the Diplopoda, previously referred to as
      sternites, are not sternal elements, but subcoxal elements associated with the
      limb base. This discovery changes the nomenclature used for the ventral plates in
      Diplopoda, with the formerly named 'sternite' better referred to as 'stigma
      carrying plate'. In helminthomorph Diplopoda, the stigma-carrying plates are
      apparently secondarily fused with the sternite. The main argument for the
      independent evolution of tracheae in insects and myriapods, the different
      location of their respective spiracles, no longer holds true. In all Myriapoda
      and Hexapoda the spiracles associated with subcoxal elements are located lateral
      to the limb base. This discovery shows that the arguments for an independent
      origin of tracheae in insects and myriapods are not uncontestable. 

PMID- 24275251
TI  - [Comment on the study "ipsilateral brachial plexus C7 root transfer. Presentation
      of a case and a literature review", by Vergara-Amador and Ramirez].

PMID- 24275252
TI  - Automated cerebrospinal fluid cell count--new reference ranges and evaluation of
      its clinical use in central nervous system infections.
AB  - OBJECTIVES: The purposes of this study were to establish new reference ranges for
      leukocytes in the CSF and to examine if the separation of mononuclear cells into
      lymphocytes and monocytes could be used to differentiate between various CNS
      infections that present with a similar picture in manual CSF cell counts. DESIGN
      AND METHODS: The automated cell counter Siemens ADVIA 2120 i was used. For the
      reference range section, we analyzed CSF from 80 neurologically healthy
      volunteers. For the differential diagnosis section we analyzed cell counts and
      hospital records from 175 patients with CSF mononuclear pleocytosis. RESULTS:
      Correlation was good between automated and manual leukocyte counts for samples
      with erythrocyte counts <250 cells/MUL. For the neurologically healthy volunteers
      studied in the reference range section, the 95th percentile was 3.0 cells/MUL for
      lymphocytes, 1.0 cell/MUL for monocytes and 1.0 cell/MUL for granulocytes. In the
      differential diagnosis section, comparisons were done between the groups Lyme
      neuroborreliosis and viral CNS infection. There were no significant differences
      between these two groups regarding cell counts; neither for lymphocytes, median
      58 cells/MUL vs. 72 cells/MUL (P = n.s.); nor for monocytes, median 13 cells/MUL
      vs. 16 cells/MUL (P = n.s.); nor for granulocytes, median 1 cell/MUL vs. 2
      cells/MUL (P = n.s.) CONCLUSIONS: We suggest new CSF cell count reference ranges
      of <4 cells/MUL for lymphocytes, <3 cells/MUL for monocytes and <3 cells/MUL for
      granulocytes. The separation of mononuclear cells into lymphocytes and monocytes
      did not facilitate the discrimination between Lyme neuroborreliosis and viral CNS
      infection.

PMID- 24275253
TI  - Identification of microRNAs predominately derived from testis and epididymis in
      human seminal plasma.
AB  - OBJECTIVES: Aiming to develop potential noninvasive biomarkers for male
      infertility, the present study is designed to identify cell-free seminal piRNAs
      (PIWI-interacting RNA), and microRNAs predominately derived from testis and
      epididymis in human semen, which is secreted from the male accessory reproductive
      organs. DESIGN AND METHODS: The ejaculate of successfully vasectomized men does
      not contain any secretion from the testis or epididymis. We screened cell-free
      seminal piRNAs, and microRNAs that predominately derived from testis/epididymis
      by comparing Solexa sequencing of seminal RNA of normozoospermic donors and
      vasectomized men, followed by quantitative PCR validation in individuals.
      RESULTS: Totally 84 seminal microRNAs exhibited levels >4-fold higher in
      normozoospermic donors than in vasectomized men. Subsequent quantitative PCR
      validation in individuals confirmed 61 microRNAs predominately secreted from
      testis/epididymis. Of these miRNAs, the lowest level in normozoospermic donors is
      >=2-fold (24 miRNAs) or 0-2-fold (37 miRNAs) more than the highest level in
      vasectomized men. Interestingly, 28 microRNAs, which contain 5 microRNA clusters
      (18 microRNAs), reside on the X-chromosome. Some microRNAs have been shown or
      predicted to target important genes in spermatogenesis or sperm maturation. At
      least 995 seminal piRNAs were identified in normozoospermic donors while were
      absent in vasectomized men. CONCLUSIONS: The present study identified cell-free
      seminal piRNAs, and microRNAs that predominately derived from testis and
      epididymis. These small noncoding RNAs might be useful noninvasive epigenetic
      markers for human male infertility researches on revealing the etiology and
      physiopathological status of impaired sperm production and maturation.

PMID- 24275254
TI  - HIV-1 Tat clade-specific cytokine induction in monocytes/macrophages is not
      evidenced in total or Vgamma9Vdelta2 T lymphocytes.
AB  - HIV-1 Tat exhibits clade-specific cytokine induction in monocytes. We
      investigated if Tat clades A-D can alter tumour necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma production by total and Vgamma9Vdelta2 T cells in vitro.
      Tat clade B, but not C, augmented TNF-alpha production by THP-1 cells. However,
      Tat clades A-D did not affect TNF-alpha or IFN-gamma production or secretion by
      resting or activated conventional and Vgamma9Vdelta2 T cells. Therefore,
      transactivation of cytokines by Tat is immune cell-specific. 

PMID- 24275256
TI  - Confirming neuropathic pain in cancer patients: applying the NeuPSIG grading
      system in clinical practice and clinical research.

PMID- 24275255
TI  - Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment -
      affect tenofovir pharmacokinetics in a large cohort of HIV-infected women.
AB  - OBJECTIVE: Tenofovir is used commonly in HIV treatment and prevention settings,
      but factors that correlate with tenofovir exposure in real-world settings are
      unknown. DESIGN: Intensive pharmacokinetic studies of tenofovir in a large,
      diverse cohort of HIV-infected women over 24 h at steady state were performed and
      factors that influenced exposure [assessed by areas under the concentration-time
      curves (AUCs)] identified. METHODS: HIV-infected women (n = 101) on tenofovir
      based therapy underwent intensive 24-h pharmacokinetic sampling. Data on
      race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant
      medications, recreational drugs and/or tobacco, hepatic and renal function,
      weight, and BMI were collected. Multivariable models using forward stepwise
      selection identified factors associated with effects on AUC. Glomerular
      filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both
      creatinine and cystatin-C measures. RESULTS: The median (range) of tenofovir AUCs
      was 3350 (1031-13 911) ng * h/ml. Higher AUCs were associated with concomitant
      ritonavir use (1.33-fold increase, P = 0.002), increasing age (1.21-fold increase
      per decade, P = 0.0007), and decreasing BMI (1.04-fold increase per 10% decrease
      in BMI). When GFR was calculated using cystatin-C measures, mild renal
      insufficiency prior to tenofovir initiation was associated with higher subsequent
      exposure (1.35-fold increase when pre-tenofovir GFR <70 ml/min, P = 0.0075).
      CONCLUSION: Concomitant ritonavir use, increasing age, decreasing BMI, and lower
      GFR prior to tenofovir initiation as estimated by cystatin C were all associated
      with elevated tenofovir exposure in a diverse cohort of HIV-infected women.
      Clinicians treating HIV-infected women should be aware of common clinical
      conditions that affect tenofovir exposure when prescribing this medication.

PMID- 24275257
TI  - Reporting of primary analyses and multiplicity adjustment in recent analgesic
      clinical trials: ACTTION systematic review and recommendations.
AB  - Performing multiple analyses in clinical trials can inflate the probability of a
      type I error, or the chance of falsely concluding a significant effect of the
      treatment. Strategies to minimize type I error probability include
      prespecification of primary analyses and statistical adjustment for multiple
      comparisons, when applicable. The objective of this study was to assess the
      quality of primary analysis reporting and frequency of multiplicity adjustment in
      3 major pain journals (ie, European Journal of Pain, Journal of Pain, and
      PAIN(r)). A total of 161 randomized controlled trials investigating noninvasive
      pharmacological treatments or interventional treatments for pain, published
      between 2006 and 2012, were included. Only 52% of trials identified a primary
      analysis, and only 10% of trials reported prespecification of that analysis.
      Among the 33 articles that identified a primary analysis with multiple testing,
      15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported
      prespecification of the adjustment methodology. Trials in clinical pain
      conditions and industry-sponsored trials identified a primary analysis more often
      than trials in experimental pain models and non-industry-sponsored trials,
      respectively. The results of this systematic review demonstrate deficiencies in
      the reporting and possibly the execution of primary analyses in published
      analgesic trials. These deficiencies can be rectified by changes in, or better
      enforcement of, journal policies pertaining to requirements for the reporting of
      analyses of clinical trial data. 

PMID- 24275258
TI  - Cancer incidence in ethnic German migrants from the Former Soviet Union in
      comparison to the host population.
AB  - AIM: To investigate cancer incidence patterns among ethnic German migrants
      (Aussiedler) from the Former Soviet Union, a large migrant group in Germany, in
      comparison to autochthonous Saarland population over a 20 year observation
      period. METHODS: Data were obtained from a cohort of Aussiedler residing in the
      federal state of Saarland (n=18,619). Cancer incidence and vital status were
      ascertained through record linkage with the Saarland Cancer Registry and local
      population registries. RESULTS: During the follow up period from 1990 to 2009 we
      observed 638 incident diagnoses of malignant neoplasms (except non-melanoma skin
      cancer). The overall standardized incidence ratio (SIR) was 0.98 (95% confidence
      interval 0.92, 1.04). However, site-specific SIRs revealed great variation.
      Stomach cancer incidence was significantly higher among Aussiedler. Lung cancer
      was elevated for males, but lower among females. Additionally, diagnoses for
      colorectal cancer among males were significantly lower. Age-standardized rates
      (ASRs) over time show not all cancer rates of Aussiedler attenuate as expected to
      Saarland rates. For example, lung and prostate cancer incidence rates show
      increasing disparity from Saarland rates and female breast cancer incidence
      develops in parallel. Furthermore, ASR for overall cancer incidence of Aussiedler
      shows a yearly decrease (p=0.06) whereas Saarland rates remain stable.
      DISCUSSION: Aussiedler incidence rates reflect incidence pattern observed in
      their countries of origin.

PMID- 24275259
TI  - Statin use and risk of prostate cancer: a Danish population-based case-control
      study, 1997-2010.
AB  - PURPOSE: Conflicting evidence has suggested that statins possess chemopreventive
      properties against prostate cancer (PCa). Therefore, we examined the association
      between statin use and risk of PCa in a Denmark-based case-control study.
      MATERIALS AND METHODS: We identified 42,480 patients diagnosed with incident PCa
      during 1997-2010 from a national cancer registry. Five age-matched population
      controls (n=212,400) were selected for each case using risk-set sampling. Statin
      use from 1996 to the index date was obtained from the National Prescription
      Registry. Odds ratios (ORs) adjusted for age, comorbidity, non-steroidal anti
      inflammatory drug use, and educational level for PCa associated with statin use,
      were computed using conditional logistic regression. Analyses were stratified by
      duration of statin use (0-1, 2-4, 5-9, or >=10 years), stage of PCa (localized or
      advanced), and type of statin used (lipophilic or hydrophilic). RESULTS: In
      total, 7915 patients (19%) and 39,384 controls (19%) redeemed statin
      prescriptions prior to the index date. Overall, statin users had a 6% lower risk
      of PCa compared with non-users [adjusted OR (ORa), 0.94; 95% confidence interval
      (CI), 0.91-0.97]. Risk estimates did not differ substantially by duration or type
      of statin used. Slightly larger statin use-associated risk reductions were
      observed for advanced PCa (ORa, 0.90; 95% CI, 0.85-0.96) and with statin use >=10
      years (ORa, 0.78; 95% CI, 0.65-0.95). CONCLUSION: Statin use was associated with
      a risk reduction overall (6%) and, specifically with advanced PCa (10%).
      Differences in diagnostic measures and residual confounding by socioeconomic
      parameters may have influenced our results.

PMID- 24275261
TI  - Production and purification of xylooligosaccharides from oil palm empty fruit
      bunch fibre by a non-isothermal process.
AB  - Oil palm empty fruit bunches (OPEFB) fibre, a by-product generated from non
      woody, tropical perennial oil palm crop was evaluated for xylooligosaccharides
      (XOS) production. Samples of OPEFB fibre were subjected to non-isothermal
      autohydrolysis treatment using a temperature range from 150 to 220  degrees C.
      The highest XOS concentration, 17.6g/L which relayed from solubilisation of 63
      g/100 g xylan was achieved at 210  degrees C and there was a minimum amount of
      xylose and furfural being produced. The chromatographic purification which was
      undertaken to purify the oligosaccharide-rich liquor resulted in a product with
      74-78% purity, of which 83-85% was XOS with degree of polymerisation (DP) between
      5 and 40.

PMID- 24275260
TI  - Community-acquired infections and their association with myeloid malignancies.
AB  - INTRODUCTION: Antigenic stimulation is a proposed aetiologic mechanism for many
      haematological malignancies. Limited evidence suggests that community-acquired
      infections may increase the risk of acute myeloid leukaemia (AML) and
      myelodysplastic syndrome (MDS). However, associations with other myeloid
      malignancies including chronic myeloid leukaemia (CML) and myeloproliferative
      neoplasms (MPNs) are unknown. MATERIALS AND METHODS: Using the Surveillance,
      Epidemiology and End Result (SEER)-Medicare database, fourteen community-acquired
      infections were compared between myeloid malignancy patients [AML (n=8489), CML
      (n=3626) diagnosed 1992-2005; MDS (n=3072) and MPNs (n=2001) diagnosed 2001-2005;
      and controls (200,000 for AML/CML and 97,681 for MDS/MPN]. Odds ratios (ORs) and
      95% confidence intervals were adjusted for gender, age and year of selection
      excluding infections diagnosed in the 13-month period prior to selection to
      reduce reverse causality. RESULTS: Risk of AML and MDS respectively, were
      significantly associated with respiratory tract infections, bronchitis (ORs 1.20
      [95% CI: 1.14-1.26], 1.25 [95% CI: 1.16-1.36]), influenza (ORs 1.16 [95% CI: 1.07
      1.25], 1.29 [95% CI: 1.16-1.44]), pharyngitis (ORs 1.13 [95% CI: 1.06-1.21], 1.22
      [95% CI: 1.11-1.35]), pneumonia (ORs 1.28 [95% CI: 1.21-1.36], 1.52 [95% CI: 1.40
      1.66]), sinusitis (ORs 1.23 [95% CI: 1.16-1.30], 1.25 [95% CI: 1.15-1.36]) as was
      cystitis (ORs 1.13 [95% CI: 1.07-1.18], 1.26 [95% CI: 1.17-1.36]). Cellulitis (OR
      1.51 [95% CI: 1.39-1.64]), herpes zoster (OR 1.31 [95% CI: 1.14-1.50]) and
      gastroenteritis (OR 1.38 [95% CI: 1.17-1.64]) were more common in MDS patients
      than controls. For CML, associations were limited to bronchitis (OR 1.21 [95% CI:
      1.12-1.31]), pneumonia (OR 1.49 [95% CI: 1.37-1.62]), sinusitis (OR 1.19 [95% CI:
      1.09-1.29]) and cellulitis (OR 1.43 [95% CI: 1.32-1.55]) following Bonferroni
      correction. Only cellulitis (OR 1.34 [95% CI: 1.21-1.49]) remained significant in
      MPN patients. Many infections remained elevated when more than 6 years of
      preceding claims data were excluded. DISCUSSION: Common community-acquired
      infections may be important in the malignant transformation of the myeloid
      lineage. Differences in the aetiology of classic MPNs and other myeloid
      malignancies require further exploration.

PMID- 24275262
TI  - Barbed versus traditional sutures: closure time, cost, and wound related outcomes
      in total joint arthroplasty.
AB  - The purpose of this study was to compare barbed sutures to traditional sutures in
      three domains: time, cost, and wound related outcomes in total knee arthroplasty
      (TKA) and total hip arthroplasty (THA). A total of 34 patients were enrolled in a
      prospective randomized controlled trial to assess time to wound closure and cost.
      In addition, a retrospective chart review of an additional 100 patients was
      conducted to further assess wound-related outcomes. On average, barbed sutures
      decreased time to wound closure by 9.72 min (P<0.05) after controlling for length
      of incision, patient's BMI and number of physicians closing. Further, using
      barbed sutures saved an average of $549.59 per case. However, increased frequency
      and severity of wound complications were associated with barbed sutures.

PMID- 24275263
TI  - Nondrainage decreases blood transfusion need and infection rate in bilateral
      total knee arthroplasty.
AB  - This retrospective study enrolled 526 patients undergoing bilateral total knee
      arthroplasties at our institution. In nondrainage group (Group 1) of 255 patients
      (510 knees), a disposable elastic sterile exsanguination tourniquet (HemaClear),
      wound closure in layers and Jones Bandage, without pre-tourniquet removal
      hemostasis or Hemovac drain were used. In drainage group (Group 2) of 227
      patients (454 knees), pneumatic tourniquet, post-deflation hemostasis, a Hemovac
      drain and Jones bandage were used. The maximal drop in hemoglobin was
      significantly greater in Group 2 than Group 1 (P < 0.001). Also infection rate
      was significantly lower in Group 1 (P = 0.017). The use of sterile tourniquet
      removed after wound closure without Hemovac drain decreases blood transfusion
      need, infection rate, tourniquet related pain and postoperative complications.

PMID- 24275264
TI  - Asymmetric bandgaps and Landau levels in a Bernal-stacked hexagonal boron-nitride
      bilayer.
AB  - A Bernal-stacked hexagonal boron-nitride (h-BN) bilayer is a two-dimensional
      polar crystal. Within the tight-binding approximation, we investigate the band
      structure of a gated h-BN bilayer by analyzing the density of states and the
      behavior of the charge transfer. We find that the bandgaps of the h-BN bilayer
      vary asymmetrically under two opposite biases due to asymmetric changes of the
      interlayer and intralayer polarities. We also find that the bias-driven net
      charge transfer between layers can be up to 0.2 electron per unit cell. Under the
      bias along one direction, the system exhibits quantum phase transitions from a
      semiconductor to a semimetal and then to a semiconductor again, whereas under the
      reverse bias, the system is always semiconducting. Besides, asymmetric Landau
      levels under opposite biases arise in the presence of a magnetic field. Moreover,
      dispersive edge states are found to exist in the bulk bandgap for an h-BN bilayer
      nanoribbon under the bias along one direction, which does not happen when the
      bias is reversed. All these properties of h-BN bilayers are measurable in
      transport experiments.

PMID- 24275265
TI  - Syphilis in the modern era: an update for physicians.
AB  - Syphilis is a complex, systemic disease caused by the spirochete Treponema
      pallidum. Syphilis is most commonly transmitted sexually or congenitally and can
      involve nearly every organ system. Its clinical progression involves several well
      characterized stages: an incubation period, a primary stage, a secondary stage, a
      latent stage, and a late or tertiary stage. Syphilis during pregnancy is a
      leading cause of perinatal mortality in sub-Saharan Africa and can cause
      spontaneous abortion, stillbirth, prematurity, low birth weight, or congenital
      syphilis. Penicillin is highly effective against syphilis and remains the
      treatment of choice. This article reviews the epidemiology, clinical features,
      diagnostic approach, treatment, and prevention of syphilis.

PMID- 24275267
TI  - Screening and management of genital chlamydial infections.
AB  - Chlamydial genital infection is common and asymptomatic in most cases. National
      screening efforts developed to educate practitioners, expand screening, and link
      testing to local health laboratories are not meeting the needs of populations at
      great risk of disease, including young racial/ethnic minority women and sexual
      minorities. The development and availability of newer diagnostics will likely
      make chlamydia testing more efficient and widely available for patients and
      providers. Practitioners are reminded to have a low threshold to offer testing
      and presumptive treatment to patients that are deemed at high risk of disease,
      particularly those who are challenging to engage in care.

PMID- 24275266
TI  - Control of Neisseria gonorrhoeae in the era of evolving antimicrobial resistance.
AB  - Neisseria gonorrhoeae has developed resistance to all previous first-line
      antimicrobial therapies over the past 75 years. Today the cephalosporins, the
      last available antibiotic class that is sufficiently effective, are also
      threatened by evolving resistance. Screening for asymptomatic gonorrhea in women
      and men who have sex with men, treating with a dual antibiotic regimen, ensuring
      effective partner therapy, and remaining vigilant for treatment failures
      constitute critical activities for clinicians in responding to evolving
      antimicrobial resistance. This article reviews the epidemiology, history of
      antimicrobial resistance, current screening and treatment guidelines, and future
      treatment options for gonorrhea.

PMID- 24275268
TI  - Trichomoniasis: the "neglected" sexually transmitted disease.
AB  - Trichomonas vaginalis is the most prevalent nonviral sexually transmitted
      infection, affecting an estimated 3.7 million people in the United States.
      Although trichomoniasis is common, it has been considered a "neglected" sexually
      transmitted disease, due to limited knowledge of its sequelae and associated
      costs. This article reviews current epidemiology, pathophysiology, diagnostic
      methods, clinical management recommendations and special considerations, research
      on associated conditions and costs, prevention strategies, and controversies
      regarding trichomoniasis.

PMID- 24275269
TI  - HPV and HPV-associated diseases.
AB  - Human papillomavirus (HPV) is the most common sexually transmitted infection. HPV
      is associated with a significant burden of disease and cancer, including
      anogenital warts and recurrent respiratory papillomatosis, and anogenital and
      oropharyngeal cancers. Effective prevention is available, including primary
      prevention of cancers and anogenital warts through HPV vaccination, and secondary
      prevention of cervical cancer through screening and treatment of precancer. This
      article focuses on HPV infection and the clinical consequences of infection, with
      attention to cervical and anogenital squamous intraepithelial neoplasia and
      anogenital warts.

PMID- 24275270
TI  - Mycoplasma genitalium: An emergent sexually transmitted disease?
AB  - This article summarizes the epidemiologic evidence linking Mycoplasma genitalium
      to sexually transmitted disease syndromes, including male urethritis, and female
      cervicitis, pelvic inflammatory disease, infertility, and adverse birth outcomes.
      It discusses the relationship of this bacterium to human immunodeficiency virus
      infection and reviews the available literature on the efficacy of standard
      antimicrobial therapies against M genitalium.

PMID- 24275272
TI  - Sexual transmission of viral hepatitis.
AB  - Identification and vaccination of adults at risk for hepatitis B virus
      acquisition through sexual contact is a key strategy to reduce new hepatitis B
      virus infections among at-risk adults. Hepatitis C has emerged as a sexually
      transmitted infection among men with male sex partners (MSM). Several biological
      and behavioral factors have been linked to hepatitis C virus transmission among
      MSM, including human immunodeficiency virus coinfection; participation in sexual
      practices that result in mucosal damage or result in exposure to blood; presence
      of sexually transmitted diseases (STIs), particularly ulcerative STIs;
      multiple/casual sex partners; and unprotected anal intercourse.

PMID- 24275273
TI  - Sexually transmitted infections. Preface.

PMID- 24275271
TI  - Pelvic inflammatory disease: current concepts in pathogenesis, diagnosis and
      treatment.
AB  - Pelvic inflammatory disease (PID) is characterized by infection and inflammation
      of the upper genital tract in women and can cause significant reproductive health
      sequelae for women. Although a definitive diagnosis of PID is made by
      laparoscopic visualization of inflamed, purulent fallopian tubes, PID is
      generally a clinical diagnosis and thus represents a diagnostic challenge.
      Therefore, diagnosis and treatment algorithms advise a high index of suspicion
      for PID in any woman of reproductive age with pelvic or abdominal pain.
      Antibiotic therapy should be started early, and given for an adequate period of
      time to reduce the risk of complications. Coverage for anaerobic organisms should
      be considered in most cases.

PMID- 24275274
TI  - Sensory substitution: closing the gap between basic research and widespread
      practical visual rehabilitation.
AB  - Sensory substitution devices (SSDs) have come a long way since first developed
      for visual rehabilitation. They have produced exciting experimental results, and
      have furthered our understanding of the human brain. Unfortunately, they are
      still not used for practical visual rehabilitation, and are currently considered
      as reserved primarily for experiments in controlled settings. Over the past
      decade, our understanding of the neural mechanisms behind visual restoration has
      changed as a result of converging evidence, much of which was gathered with SSDs.
      This evidence suggests that the brain is more than a pure sensory-machine but
      rather is a highly flexible task-machine, i.e., brain regions can maintain or
      regain their function in vision even with input from other senses. This
      complements a recent set of more promising behavioral achievements using SSDs and
      new promising technologies and tools. All these changes strongly suggest that the
      time has come to revive the focus on practical visual rehabilitation with SSDs
      and we chart several key steps in this direction such as training protocols and
      self-train tools. 

PMID- 24275275
TI  - BiVap saline vaporization of the prostate in men with benign prostatic
      hyperplasia: our clinical experience.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and postoperative outcomes of the
      recently developing endoscopic technique of BiVap saline vaporization of the
      prostate in patients with benign prostatic obstruction (BPO). METHODS: Ninety-six
      patients who underwent transurethral resection of the prostate with BiVap system
      for BPO and with available data during the 1-year postoperative follow-up period
      were included in the study. All patients were evaluated at the postoperative 1st,
      3rd, 6th, and 12th month, and preoperative and postoperative values of
      International Prostate Symptom Score (IPSS), quality of life (QoL) score, total
      prostate-specific antigen, International Index of Erectile Function 15,
      postvoiding residual urinary volume (PVR), maximum urinary flow rate (Qmax), and
      average urinary flow rate (Qave) were compared. Statistical analyses were
      performed with SPSS version 18. A P value <.05 was considered significant.
      RESULTS: Mean age of the patients was 65.6 +/- 7.5 years. Significant improvement
      was noted for IPSS, Qmax, Qave, PVR, and QoL score by the postoperative first
      month when compared with the preoperative values. Maximum improvement in the
      IPSS, Qmax, Qave, PVR, and QoL score was achieved at postoperative 6th, 3rd, 6th,
      12th, and 3rd months, respectively. Although total International Index of
      Erectile Function and subgroup scores decreased at the postoperative first month,
      all improved to their preoperative levels by the postoperative third month.
      CONCLUSION: BiVap system is a safe, effective, and useful technique, which can be
      easily performed in patients with BPO.

PMID- 24275276
TI  - Severe penile injuries in children and adolescents: reconstruction modalities and
      outcomes.
AB  - OBJECTIVE: To review our experience with severe penile trauma, mechanism of
      injury, and their treatment modalities in 16 children younger than 18 years.
      Management of penile trauma poses diverse challenges to the reconstructive
      urologist, as injuries vary from abrasions to total emasculation. METHODS:
      Analysis of 16 patients with severe penile injuries referred to us between 2002
      and 2011 was undertaken. The median age at surgery was 13 years (range, 5-17).
      Etiology of penile trauma and choice of treatment were evaluated. The management
      included a wide variety of surgical techniques that were tailored to the
      individual patient. Results were analyzed to define etiology, that is, mechanism
      of penile injury and to estimate modalities of surgical management and
      postoperative outcomes. Also, postoperative questionnaire was used, which
      included questions on functioning and esthetical appearance of participating
      patients and overall satisfaction. RESULTS: The causes of penile injury in these
      series were traffic accidents (2), iatrogenic trauma (5), self-amputation (1),
      electrocution (1), burns (3), dog bite (2), zipper injury (1), and mother's hair
      strangulation (1). The mean follow-up was 46 months (range, 14-122), and
      examinations were uneventful, except for 2 fistulae formation after neophallic
      urethral reconstruction. CONCLUSION: The main goal of reconstructive surgery is
      to have a penis with normal appearance and functions. Severe penile injuries
      should be treated on a case-by-case basis using the most propitious techniques.

PMID- 24275277
TI  - Reply: To PMID 24275278.

PMID- 24275278
TI  - Editorial comment.

PMID- 24275279
TI  - Robotic vs open simple enucleation for the treatment of T1a-T1b renal cell
      carcinoma: a single center matched-pair comparison.
AB  - OBJECTIVE: To compare surgical, pathological, short-term functional data, and
      complications of endoscopic robotic-assisted simple enucleation (ERASE) and open
      simple enucleation (OSE). METHODS: We undertook matched-pair analysis (age, tumor
      size, and preoperative aspects and dimensions used for an anatomical [PADUA]
      score) of 392 patients treated with simple enucleation (SE) for T1a-T1b renal
      tumors in our department, including 160 patients in the OSE group and 80 in the
      ERASE group. Perioperative outcomes were compared with univariate analysis.
      Variables associated with warm ischemia time (WIT) >25 minutes, complications,
      and postoperative acute kidney dysfunction (AKD) were assessed with multivariate
      analysis. RESULTS: The groups were comparable in body mass index (BMI),
      comorbidity, and preoperative renal function. In the ERASE vs the OSE group, no
      significant differences resulted regarding WIT (18.5 vs 16.4 minutes, P = .5),
      complications, transfusion rate, reoperation rate for Clavien grade >= 3
      complications, and positive surgical margin rate (2.9% vs 2.1%, P = .63). In
      elective patients, no significant difference resulted in variation of estimated
      glomerular filtration rate from baseline (8.5 vs 13.9 mL/min, P = .17) and AKD.
      In the ERASE group, the clamping of renal pedicle was used with a lower frequency
      (P <.0001), with lower estimated blood loss (EBL), longer operative time, and a 1
      day shorter hospitalization (P = .001). On the multivariate analysis, the
      surgical approach was not independently associated with WIT >25 minutes,
      postoperative complications, and AKD. CONCLUSION: The ERASE is a feasible
      technique with a positive surgical margin rate comparable to OSE; it showed WIT
      and complication rates similar to the open approach, along with the advantages of
      mini-invasivity.

PMID- 24275280
TI  - Reply: To PMID 24275282.

PMID- 24275281
TI  - Pre-emptive penile ring block with sucrose analgesia reduces pain response to
      neonatal circumcision.
AB  - OBJECTIVE: To compare retrospective use of oral sucrose (SUC) vs oral sucrose
      plus lidocaine ring block (SUC + RB) in the management of pain during neonatal
      circumcision. METHODS: A retrospective review of medical records of newborns
      circumcised using the "Neonatal Infant Pain Scale" was done. RESULTS: With regard
      to pain, the SUC group had a significantly greater percentage of those with pain
      than the SUC + RB group at 1 minute (77.7% vs 69.4%; P = .01) and 5 minutes
      (65.7% vs 55.7%; P = .004). There was no significant pain difference at 30
      minutes. In the multivariate logistic regression analyses, those in the SUC group
      had significantly greater odds for pain at 1 minute than those in the SUC + RB
      group (odds ratio 1.45, 95% confidence interval 1.04-2.02; P = .03). No
      significant difference was noted at 5 minutes. Each of the SUC and SUC + RB
      groups had significant decreases in pain percentages at 5 minutes and 30 minutes
      (P <.001). In addition, post-term gestational age had significantly greater odds
      for pain at 5 minutes (odds ratio 3.67, 95% confidence interval 1.51-8.93; P =
      .004). CONCLUSION: We found that sucrose use alone as compared with sucrose and
      ring block combined had greater odds for pain at 1 minute but not at 5 minutes.
      In addition, those with post-term gestational age had greater odds for pain at 5
      minutes as compared with those with regular gestational age. We recommend for
      hospital-based circumcision using clamps, the use of combined sucrose and ring
      block for increased analgesia. In addition, for post-term neonates, we recommend
      greater focus on pain levels, including considering higher dosages of pain
      medications.

PMID- 24275282
TI  - Measurement of ureteric stone diameter in different planes on multidetector
      computed tomography--impact on the clinical decision making.
AB  - OBJECTIVE: To determine if the measurement of ureteric stone in coronal
      reconstruction plane is different from the measurement in axial plane and whether
      the difference can impact the management decision in patients with ureteric
      colic. METHODS: All patients who underwent unenhanced multidetector computed
      tomographic (MDCT) scan for the evaluation of reno-ureteral colic in outpatient
      clinics and emergency room were evaluated. The scans were evaluated on Picture
      Archiving Computer System with a 3-mm axial and reformatted 3-mm coronal
      sections. Maximal stone diameter was measured in 2 dimensions in the axial and
      reformatted coronal sections by 2 reviewers. Only scans with isolated,
      unilateral, solitary ureteric calculi were included in the final analysis. All
      patients were monitored up to 4 weeks after MDCT to determine the clinical
      outcome. RESULTS: A total of 331 patients (272 male and 59 female; mean age +/-
      standard deviation, 39.8 +/- 13.8 years) were included. One hundred seventy-one
      (51.7%) stones passed spontaneously during the follow-up period. There was a 20%
      underestimation of maximal stone diameter in axial plane for all stones and a 17%
      for the stones that passed spontaneously or with medical expulsive therapy, as
      compared with measurement on coronal reconstruction. CONCLUSION: Measuring the
      transverse stone diameter on axial images of MDCT scan underestimates size of
      ureteric stone. This can have an impact on counseling of patients and their
      clinical outcome, coronal reformatted images be used for size estimation.

PMID- 24275283
TI  - Prostate type epithelial polyps of urogenital tract: a series of 3 cases and
      literature review.
AB  - OBJECTIVE: To present clinicopathologic and immunohistochemical features of 3
      cases of rare and unusual condition of urogenital tract, prostatic epithelial
      polyps situated in various parts of the urinary tract, with a heterogeneous
      presentation and a benign behavior. METHODS: Detailed data on 3 patients with
      polyps in the urinary tract presented from January 2008 to December 2012 were
      reviewed, and the clinicopathologic characteristics of the patients and disease
      along with various diagnostic and treatment modalities were recorded. RESULTS:
      All the 3 patients were aged older than 45 years. The presenting symptom
      hematuria was common to each patient. One patient had polypoidal growth in
      preprostatic (intramural) urethra; the other 2 had polyps in bladder. Each
      patient had other urogenital tract disease, 2 were known case of benign prostatic
      hyperplasia, and 1 had past history of urinary bladder carcinoma. Clinically,
      each of the case was misdiagnosed as aggressive lesions; however, after
      histopathologic diagnosis, management was undertaken according to benign result.
      No recurrence or metastasis was observed to date. Immunohistochemical stain
      prostate-specific antigen was positive in the epithelium. All 3 patients were
      recurrence-free on follow-up. CONCLUSION: The prostate type epithelial polyps are
      rare in urinary bladder and bladder urethra and are frequently associated with
      concurrent pathologies of urogenital tract. These are benign conditions with
      differential of other benign and malignant disorders.

PMID- 24275284
TI  - Micturitional urethral pressure profilometry for the diagnosis, grading, and
      localization of bladder outlet obstruction in adult men: a comparison with
      pressure-flow study.
AB  - OBJECTIVE: To investigate the accuracy of micturitional urethral pressure
      profilometry (MUPP) for diagnosis, grading, and localization of bladder outlet
      obstruction (BOO) in men with obstructive lower urinary tract symptoms. METHODS:
      This prospective study included adult men with voiding symptoms qualifying for
      urodynamics (UDS). Patients with urethral stricture, urinary-tract infection, and
      inflammatory diseases of the bladder were excluded. Patients were subjected to
      UDS followed by VCUG the same day. UDS was performed using Solar Silver (MMS
      International, Enschede, the Netherlands) and included uroflowmetry, resting
      cystometry with UPP, pressure-flow study with MUPP, and perineal surface
      electromyography. The study was performed in accordance with International
      Continence Society Good Urodynamic-practice Guidelines (2002). VCUG was
      considered the gold standard for presence and localization of BOO. RESULTS: A
      total of 64 male patients with mean age 53.3 +/- 17.8 years and International
      Prostate Symptom Score 17.2 +/- 6.8 completed the study. Uroflowmetry revealed
      maximum urine flow 10.1 +/- 7.1 mL/s, voided-volume 218.9 +/- 161.6 mL, and
      postvoid residue 129.8 +/- 126.5 mL. For diagnosis of BOO, Abrams-Griffith
      number, Schaefer obstruction-grades, and obstruction-coefficient had weak
      agreement with VCUG (Cohen's kappa k <0.20), whereas urethral closure-pressure
      (Pclo) had strong agreement (k = 0.78). For grading, Pclomax had a significant
      positive linear correlation with Abram-Griffiths number (R(2) = 0.562; P =
      .0001). MUPP was able to localize the site of obstruction correctly in 55 of 57
      obstructed patients. CONCLUSION: MUPP is highly accurate in diagnosis, grading,
      and localization of BOO in men with voiding dysfunction. It might be a useful
      supplement to VCUG/UDS.

PMID- 24275285
TI  - SIU/ICUD Consultation on Urethral Strictures: Evaluation and follow-up.
AB  - For the 2010 International Consultation on Urethral Strictures, all available
      published data relating to the evaluation and follow-up of patients with anterior
      urethral stricture or posterior urethral stenosis were reviewed and evaluated.
      Selected manuscripts were classified by Level of Evidence using previously
      established criteria. Consensus was achieved through group discussion, and formal
      recommendations were established and graded on the basis of levels of evidence
      and expert opinion. Retrograde urethrography remains the de facto standard for
      the evaluation of patients with urethral stricture. It can readily be combined
      with voiding cystourethrography to achieve a synergistic evaluation of the entire
      urethra, and this approach is currently recommended as the optimal method for
      pretreatment staging. Cystoscopy is recommended as the most specific procedure
      for the diagnosis of urethral stricture and is a useful adjunct in the staging of
      anterior urethral stricture, particularly to confirm abnormal or equivocal
      findings on imaging studies. Cystoscopy is also an important modality for
      assessing the bladder neck and posterior urethra in the setting of a pelvic
      fracture-related urethral injury. Although urethrography and cystoscopy remain
      the principle forms of assessment of the patient with urethral stricture,
      additional adjuncts include uroflowmetry, symptom scores, quality of life
      assessments, ultrasonography, computed tomography, and magnetic resonance
      imaging. These modalities might be helpful to further evaluate patients in select
      circumstances or provide a less invasive approach to monitoring outcomes after
      surgical treatment. Further research is needed to establish consensus opinion as
      to the definition of success after urethroplasty and to develop standardized
      patient outcome measures. 

PMID- 24275286
TI  - Interleukin 10 reduces testicular damage in experimental testicular
      ischemia/reperfusion injury.
AB  - OBJECTIVE: To evaluate the protective effect of interleukin 10 (IL-10) on
      biochemical and histopathologic changes in experimental testicular ischemia or
      reperfusion injury (RI) in rats. METHODS: Sprague-Dawley rats were randomly
      divided into 3 groups, each containing 7 rats; sham-control, I-R/untreated group,
      and I/R treated with IL-10. The ischemia period was 6 hours, and orchiectomy was
      performed after 1 hour of detorsion. IL-10 was given intraperitoneally in a
      period of 10 minutes before reperfusion. In all groups, ipsilateral orchiectomies
      were performed to make histologic examination and biochemical analysis such as
      malondialdehyde, glutathione peroxidase, and myeloperoxidase (MPO). RESULTS: IL
      10 treatment significantly decreased the I-R-induced elevation in testes
      malondialdehyde levels. In the I-R/IL-10-treated group, testes glutathione
      peroxidase levels were increased compared with the I-R/untreated group rats. MPO
      activities were significantly increased in the testes tissues of the I
      R/untreated group. However, in the I-R/IL-10-treated group, MPO levels
      significantly decreased. Histopathologically, in the I-R/untreated group rats,
      edema, congestion, hemorrhage among seminiferous tubules, and necrosis of the
      germinal cells were predominant features in sections. The testicular injury score
      was lower in the IL-10-treated group rats compared with the I-R/untreated group.
      CONCLUSION: IL-10 might play a protective role in reducing reperfusion injury.

PMID- 24275287
TI  - The use of bovine pericardium for complex urologic venous reconstruction.
AB  - OBJECTIVE: To describe the use of bovine pericardium (BP) in several scenarios
      for venous patching and as a tubularized graft in urologic surgery. METHODS: BP
      was used as patch or tubularized graft in 7 patients between 2010 and 2013.
      Clinical scenarios and operative indications were reviewed. We used BP as a patch
      graft for the inferior vena cava (IVC) (N = 3) and for the iliac venous system (N
      = 1) to restore venous outflow. Tubularized grafts were used (N = 2) to replace
      the left renal vein in oncology procedures and during renal autotransplantation
      (N = 1). Surgical technique is reviewed in detail. RESULTS: We used BP as a
      venous patching in 4 cases and as a tubularized graft in 3 cases. There was no
      evidence of venous thrombosis of the replaced system with a mean of 14.8 months
      (range, 9-26) follow-up. CONCLUSION: The use of BP as a patch or tubularized
      graft is an option for complicated urologic venous reconstruction. Although the
      follow-up interval is relatively short and this initial series small, our initial
      results are promising.

PMID- 24275288
TI  - Editorial comment.

PMID- 24275290
TI  - The epidemiology of heart failure in adults with congenital heart disease.
AB  - The impact of lifelong exposure to myocardial dysfunction in populations with
      congenital heart disease (CHD) is becoming increasingly recognized. Most children
      born with CHD now reach adulthood and the long-term sequelae of treatment are
      contributing to substantial comorbidity. The combination of structural changes
      present at birth with changes resulting from cardiac surgery can result in heart
      failure. This article reports on the current state of knowledge on the
      epidemiology of heart failure in this patient population.

PMID- 24275291
TI  - Imaging for the assessment of heart failure in congenital heart disease:
      ventricular function and beyond.
AB  - Although heart failure is a diagnosis made on clinical grounds, cardiac imaging
      remains essential for quantifying ventricular remodeling and function, and for
      identifying potentially reversible causes of heart failure. Various nongeometric
      methods for the assessment of ventricular function have been developed, and 3
      dimensional imaging is also gaining ground in its clinical applications. This
      review focuses on the application of noninvasive imaging strategies in the
      assessment of heart failure in congenital heart disease, specifically
      echocardiography, cardiac magnetic resonance imaging, and computed tomography.
      Both traditional and emerging techniques are discussed, and their potential
      applications and limitations explored.

PMID- 24275289
TI  - Hippocampal mossy fiber leu-enkephalin immunoreactivity in female rats is
      significantly altered following both acute and chronic stress.
AB  - Research indicates that responses to stress are sexually dimorphic, particularly
      in regard to learning and memory processes: while males display impaired
      cognitive performance and hippocampal CA3 pyramidal cell dendritic remodeling
      following chronic stress, females exhibit enhanced performance and no remodeling.
      Leu-enkephalin, an endogenous opioid peptide found in the hippocampal mossy fiber
      pathway, plays a critical role in mediating synaptic plasticity at the mossy
      fiber-CA3 pyramidal cell synapse. Estrogen is known to influence the expression
      of leu-enkephalin in the mossy fibers of females, with leu-enkephalin levels
      being highest at proestrus and estrus, when estrogen levels are elevated. Since
      stress is also known to alter the expression of leu-enkephalin in various brain
      regions, this study was designed to determine whether acute or chronic stress had
      an effect on mossy fiber leu-enkephalin levels in females or males, through the
      application of correlated quantitative light and electron microscopic
      immunocytochemistry. Both acute and chronic stress eliminated the estrogen
      dependence of leu-enkephalin levels across the estrous cycle in females, but had
      no effect on male levels. However, following acute stress leu-enkephalin levels
      in females were consistently lowered to values comparable to the lowest control
      values, while following chronic stress they were consistently elevated to values
      comparable to the highest control values. Ultrastructural changes in leu
      enkephalin labeled dense core vesicles paralleled light microscopic observations,
      with acute stress inducing a decrease in leu-enkephalin labeled dense core
      vesicles, and chronic stress inducing an increase in leu-enkephalin labeled dense
      core vesicles in females. These findings suggest that alterations in leu
      enkephalin levels following stress could play an important role in the sex
      specific responses that females display in learning processes, including those
      important in addiction. 

PMID- 24275292
TI  - Exercise physiology and testing in adult patients with congenital heart disease.
AB  - As the longevity of patients with congenital heart disease improves, the number
      surviving to adulthood will continue to rise. Consequently, practicing physicians
      can expect to encounter an increasing number of adult patients with various
      congenital cardiac conditions. Impaired exercise tolerance in this patient
      population is exceptionally common; adult patients with congenital heart disease
      have reduced exercise capacity compared with healthy, age-matched counterparts.
      The different methods of evaluating exercise capacity, the characteristic
      physiologic abnormalities encountered in patients with various congenital cardiac
      conditions, the pathophysiologic mechanisms that may account for these
      abnormalities, and the clinical implications of these findings are discussed.

PMID- 24275293
TI  - Psychosocial functioning and quality of life in adults with congenital heart
      disease and heart failure.
AB  - Complex congenital heart disease (CHD) is a chronic medical condition to which
      patients are expected to adapt throughout their lives. Many patients are at risk
      of developing heart failure in adulthood and their comprehensive care requires an
      interdisciplinary approach. North American studies indicate that adults with CHD
      are at increased risk of psychosocial difficulties. Research suggests that adults
      with heart failure caused by acquired heart disease are also likely to experience
      impaired psychosocial functioning and quality of life (QOL). Thus, adults with
      CHD who develop heart failure are a particularly vulnerable group with regard to
      psychosocial functioning and QOL.

PMID- 24275294
TI  - Biomarkers in adult congenital heart disease heart failure.
AB  - Most adults with congenital heart disease show high levels of natriuretic peptide
      (NP) when compared with normal controls. Levels of norepinephrine and NP were
      strongly related to outcome in studies that included many symptomatic patients,
      especially those with unrepaired congenital heart disease, Eisenmenger syndrome,
      and pulmonary hypertension. Limited data are available regarding serial
      assessment of biomarkers; such information could provide additional important
      information to help identify patients at risk, as demonstrated during patient
      follow-up and pregnancy.

PMID- 24275295
TI  - Diagnostic tools for arrhythmia detection in adults with congenital heart disease
      and heart failure.
AB  - As patients with congenital heart disease age with increasingly complex lesions,
      heart failure and arrhythmias have emerged as leading sources of morbidity and
      mortality. The two are intertwined, as one may herald, beget, or aggravate the
      other. Moreover, arrhythmias in adults with congenital heart disease and heart
      failure can be poorly tolerated or life threatening. There is, therefore, much
      interest in promptly and accurately diagnosing arrhythmias and identifying risk
      factors for sudden death. This article appraises current knowledge regarding
      diagnostic tools for arrhythmias in adults with congenital heart disease and
      heart failure and comments on their prognostic value where relevant.

PMID- 24275296
TI  - Electrophysiologic therapeutics in heart failure in adult congenital heart
      disease.
AB  - Arrhythmias have long been recognized as a major cause of morbidity and mortality
      in the adult with congenital heart disease. It is important that the clinician
      accurately diagnoses these disturbances and is cognizant of the full array of
      antiarrhythmic agents and devices available to treat these conditions. This
      review discusses the most common arrhythmias encountered in this population and
      the therapeutic options available. Specific issues unique to this population are
      also addressed.

PMID- 24275297
TI  - The exceptional and far-flung manifestations of heart failure in Eisenmenger
      syndrome.
AB  - Dramatic advances in the diagnosis and treatment of congenital heart disease
      (CHD), the most common inborn defect, has resulted in a growing population of
      adults with CHD. Eisenmenger syndrome (ES) represents the extreme form of
      pulmonary arterial hypertension associated with CHD, characterized by markedly
      increased pulmonary vascular resistance with consequently reversed or
      bidirectional shunting. While ES is a direct consequence of a heart defect, it is
      a fundamentally multisystem syndrome with wide-ranging clinical manifestations.
      The introduction of targeted pulmonary hypertension therapies aimed has subtly
      shifted clinical focus from preventing iatrogenic and other adverse events toward
      cautious therapeutic activism.

PMID- 24275298
TI  - Failure of the fontan circulation.
AB  - The essence of a Fontan circuit is the creation of the Fontan "neoportal system,"
      which allows for oxygenation at near normal levels, but at the cost of a chronic
      state of systemic venous congestion and decreased cardiac output. The heart,
      while still the engine of the circuit, cannot compensate for this major flow
      restriction: the ventricle has lost control of the output and venous congestion.
      Systolic and diastolic ventricular dysfunction may aggravate the hemodynamic
      burden. The abnormal hemodynamics affects organs outside the heart and may lead
      to liver cirrhosis/malignancy, protein-losing enteropathy, or plastic bronchitis.
      The chronic low flow state causes an increase of pulmonary (and systemic)
      vascular resistance and ventricular filling pressures, causing failure of the
      Fontan to be progressive with increasing functional impairment.

PMID- 24275299
TI  - Pregnancy in women with heart disease: risk assessment and management of heart
      failure.
AB  - Heart disease, present in 0.5% to 3% of pregnant women, is an important cause of
      morbidity and the leading cause of death among pregnant women in the developed
      world. Certain heart conditions are associated with an increased risk of heart
      failure during pregnancy or the postpartum period; for these conditions,
      management during pregnancy benefits from multidisciplinary care at a center with
      expertise in pregnancy and heart disease. This article focuses on cardiac risks
      and management strategies for women with acquired and congenital heart disease
      who are at increased risk of heart failure during pregnancy.

PMID- 24275300
TI  - The tricuspid valve in adult congenital heart disease.
AB  - The tricuspid valve is frequently affected in adults with congenital heart
      disease but is also frequently overlooked. Disease of this valve can occur
      primarily or develop secondary to changes in the right ventricle caused by other
      disease states. The embryology and anatomy of the tricuspid valve are important
      to understanding pathogenesis of valve dysfunction in congenital heart disease.
      Clinical findings can be subtle. Multimodality imaging may be necessary to fully
      assess the cause and impact of tricuspid valve lesions. More research is needed
      in pathophysiology, imaging, and treatment in this area.

PMID- 24275301
TI  - Heart failure caused by congenital left-sided lesions.
AB  - There are diverse mechanisms by which congenital left-sided cardiac lesions can
      precipitate heart failure. Left heart outflow obstruction can impose abnormal
      pressure load on the left ventricle, inducing adverse remodeling, hypertrophy,
      and diastolic and systolic dysfunction. Abnormalities in left ventricular inflow
      can increase pulmonary venous pressure and predisposing to pulmonary edema. In
      addition, inborn abnormalities in left ventricular myocardial structure and
      function can impair both systolic and diastolic function and manifest as heart
      failure later in life. In this article, the different mechanisms, outcomes, and
      treatments of heart failure in patients with congenital left-sided lesions are
      discussed. 

PMID- 24275302
TI  - Medical therapy in adults with congenital heart disease.
AB  - Heart failure is a common late complication in adults with congenital heart
      defects, both repaired and unrepaired. The onset of clinical heart failure is
      associated with increased morbidity and mortality. Some patients with congenital
      heart disease may benefit from medications shown to improve survival in the
      population with acquired heart failure, but these same therapies may be of no
      benefit to other patients. Further studies are needed to better guide the choice
      of medical therapies. 

PMID- 24275303
TI  - Percutaneous options for heart failure in adults with congenital heart disease.
AB  - In the context of congenital heart disease (CHD), the complex biochemical and
      physiologic response to the pressure- or volume-loaded ventricle can be induced
      by stenotic and shunt/regurgitant lesions, respectively. A range of transcatheter
      therapies have recently emerged to expand the therapeutic potential of the more
      traditional surgical and medical interventions for heart failure in patients with
      CHD. Together, these complementary interventions aim to treat the growing patient
      population with adult CHD (ACHD). In this article, the most commonly used
      transcatheter interventions for heart failure in patients with ACHD are reviewed.

PMID- 24275304
TI  - Surgical device therapy for heart failure in the adult with congenital heart
      disease.
AB  - Individuals with adult congenital heart disease (ACHD) are at a great risk for
      heart failure, and the underlying anatomic features are important predictors of
      heart failure. As the ACHD population grows older, multiple events, including
      years of an altered physiology, the neurohormonal cascade, and many still
      unknown, culminate in ventricular failure. Surgical device therapy is an
      effective method in supporting patients with heart failure. Ventricular assist
      devices have been used with success in bridging ACHD patients to heart
      transplantation or destination therapy.

PMID- 24275305
TI  - Heart transplantation in adults with congenital heart disease.
AB  - Heart transplantation has become an increasingly common and effective therapy for
      adults with end-stage congenital heart disease (CHD) because of advances in
      patient selection and surgical technique. Indications for transplantation in CHD
      are similar to other forms of heart failure. Pretransplant assessment of CHD
      patients emphasizes evaluation of cardiac anatomy, pulmonary vascular disease,
      allosensitization, hepatic dysfunction, and neuropsychiatric status. CHD patients
      experience longer waitlist times and higher waitlist mortality than other
      transplant candidates. Adult CHD patients undergoing transplantation carry an
      early hazard for mortality compared with non-CHD recipients, but by 10 years
      posttransplant, CHD patients have a slight actuarial survival advantage.

PMID- 24275306
TI  - Heart failure in congenital heart disease: a confluence of acquired and
      congenital.
AB  - Heart failure (HF) is a common cause of morbidity and mortality in congenital
      heart disease (CHD), with increasing prevalence because of improved treatment
      options and outcomes. Genetic factors and acquired postnatal factors in CHD might
      play a major role in the progression to HF. This article proposes 3 routes that
      lead to HF in CHD: rare monogenic entities that cause both CHD and HF; severe CHD
      lesions in which acquired hemodynamic effects of CHD or surgery result in HF;
      and, most commonly, a combined effect of complex genetics in overlapping pathways
      and acquired stressors caused by the primary lesion. 

PMID- 24275307
TI  - Adults with congenital heart disease: growing pains.

PMID- 24275308
TI  - Evolving perspectives on heart failure in adults with congenital heart disease.
      Preface.

PMID- 24275309
TI  - Spatial modulation of above-the-gap cathodoluminescence in InP nanowires.
AB  - We report the observation of light emission on wurtzite InP nanowires excited by
      fast electrons. The experiments were performed in a scanning transmission
      electron microscope using an in-house-built cathodoluminescence detector. Besides
      the exciton emission, at 850 nm, emission above the band gap from 400 to 800 nm
      was observed. In particular, this broad emission presented systematic periodic
      modulations indicating variations in the local excitation probability. The
      physical origin of the detected emission is not clear. Measurements of the
      spatial variation of the above-the-gap emission points to the formation of leaky
      cavity modes of a plasmonic nature along the nanowire length, indicating the wave
      nature of the excitation. We propose a phenomenological model, which fits closely
      the observed spatial variations. 

PMID- 24275310
TI  - Comparative efficacy and safety of medical treatments for the management of
      overactive bladder: a systematic literature review and mixed treatment
      comparison.
AB  - CONTEXT: Overactive bladder (OAB) treatment guidelines recommend antimuscarinics
      as first-line pharmacologic therapy. Mirabegron is a first-in-class beta3
      adrenoceptor agonist licensed for the treatment of OAB and has shown to be well
      tolerated and effective in the treatment of OAB symptoms. OBJECTIVE: To assess
      the relative efficacy and tolerability of OAB medications, specifically
      mirabegron 50 mg versus antimuscarinics in patients with OAB. EVIDENCE
      ACQUISITION: A systematic literature search was performed on published peer
      reviewed articles from 2000 to 2013. This review included randomised controlled
      trials (RCTs) studying changes in symptoms (micturition frequency, incontinence,
      and urgency urinary incontinence [UUI] episodes) and incidence of the most
      frequently reported adverse events (dry mouth, constipation) associated with
      current OAB medications. The following drugs were considered in addition to
      mirabegron: darifenacin, tolterodine immediate release (IR) and extended release
      (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed
      treatment comparisons (MTCs) were performed for efficacy (micturition,
      incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision).
      EVIDENCE SYNTHESIS: Overall, 44 RCTs involving 27,309 patients were included. The
      MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in
      reducing the frequency of micturition incontinence and UUI episodes, with the
      exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in
      improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an
      incidence of dry mouth similar to placebo and significantly lower than all
      included antimuscarinics. CONCLUSIONS: Mirabegron 50 mg had similar efficacy to
      most antimuscarinics and lower incidence of dry mouth, the most common adverse
      event reported with antimuscarinics and one of the main causes of discontinuation
      of treatment. Despite being a powerful tool for evidence-based health care
      evaluation, the Bayesian MTC method has limitations. Further head-to-head
      comparisons between mirabegron and antimuscarinics should be conducted to confirm
      our results.

PMID- 24275311
TI  - R-LESS partial nephrectomy trifecta outcome is inferior to multiport robotic
      partial nephrectomy: comparative analysis.
AB  - BACKGROUND: Trifecta achievement in partial nephrectomy (PN) is defined as the
      combination of warm ischemia time <= 20 min, negative surgical margins, and no
      surgical complications. OBJECTIVE: To compare trifecta achievement between
      robotic, laparoendoscopic, single-site (R-LESS) PN and multiport robotic PN
      (RPN). DESIGN, SETTING, AND PARTICIPANTS: Data from 167 patients who underwent
      RPN from 2006 to 2012 were retrospectively analyzed. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Primary outcome measurement was trifecta achievement;
      secondary outcome was the perioperative and postoperative comparison between
      groups. The measurements were estimated and analyzed with SPSS v.18 using
      univariable, multivariable, and subgroup analyses. RESULTS AND LIMITATIONS:
      Eighty-nine patients were treated with RPN and 78 were treated with R-LESS PN.
      Baseline characteristics of both groups were similar. Trifecta was achieved in 38
      patients (42.7%) in the multiport RPN group and 20 patients (25.6%) in the R-LESS
      PN group (p=0.021). Patients in the R-LESS PN group had longer mean operative
      time, warm ischemia time, and increased estimated glomerular filtration rate
      (eGFR) percentage change. No significant differences were found between the two
      groups in days of hospitalization, blood loss, postoperative eGFR, positive
      surgical margins, and surgical complications. Patients with increased PADUA and
      RENAL scores, infiltration of the collecting system, and renal sinus involvement
      had an increased probability of not achieving the trifecta. In regression
      analysis, the type of procedure and the tumor size could predict trifecta
      accomplishment (p=0.019 and 0.043, respectively). The retrospective study, the
      low number of series, and the controversial definition of trifecta were the main
      limitations. CONCLUSIONS: The trifecta was achieved in significantly more
      patients who underwent multiport RPN than those who underwent R-LESS PN. R-LESS
      PN could be an alternative option for patients with decreased tumor size, low
      PADUA and RENAL scores, and without renal sinus or collecting system involvement.
      PATIENT SUMMARY: In this study, we looked at the outcomes of patients who had
      undergone robotic partial nephrectomy. We found that conventional robotic partial
      nephrectomy is superior to R-LESS partial nephrectomy with regard to the
      accomplishment of negative margins, reduced warm ischemia time, and minimal
      surgical complications.

PMID- 24275312
TI  - Human hepatoma cells exposed to estuarine sediment contaminant extracts permitted
      the differentiation between cytotoxic and pro-mutagenic fractions.
AB  - Complex toxicant mixtures present in estuarine sediments often render contaminant
      screening unfeasible and compromise determining causation. HepG2 cells were
      subjected to bioassays with sediment extracts obtained with a series of
      progressively polar solvents plus a crude extract. The sediments were collected
      from an impacted area of an estuary otherwise regarded as pristine, whose
      stressors result mostly from aquaculture effluents and hydrodynamic shifts that
      enhance particle deposition. Compared to a reference scenario, the most polar
      extracts yielded highest cytotoxicity while higher genotoxicity (including
      oxidative damage) was elicited by non-polar solvents. While the former caused
      effects similar to those expected from biocides, the latter triggered effects
      compatible with known pro-mutagens like PAHs, even though the overall levels of
      toxicants were considered of low risk. The results indicate that the approach may
      constitute an effective line-of-evidence to infer on the predominant set of
      hazardous contaminants present in complex environmental mixtures. 

PMID- 24275313
TI  - The characteristics of Beijing aerosol during two distinct episodes: impacts of
      biomass burning and fireworks.
AB  - The chemical composition of Beijing aerosol was measured during summer and
      winter. Two distinct episodes were identified. Water-soluble potassium (K(+))
      increased significantly during the firework episode in winter with an episode to
      non-episode ratio of 4.97, whereas the biomass burning (BB) episode in summer was
      characterized by high episode to non-episode ratios of levoglucosan (6.38) and
      K(+) (6.90). The BB and firework episodes had only a minor influence on the water
      soluble OC (organic carbon) to OC ratio. Based on separate investigations of
      episode and non-episode periods, it was found that: (i) sulfate correlated
      strongly with both relative humidity and nitrate during the typical winter period
      presumably indicating the importance of the aqueous-phase oxidation of sulfur
      dioxide by nitrogen dioxide, (ii) oxalate and WSOC during both winter and summer
      in Beijing were mainly due to secondary formation, and (iii) high humidity can
      significantly enhance the formation potential of WSOC in winter. 

PMID- 24275314
TI  - Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX
      ovarian cancer cells.
AB  - Chemotherapy could be used as an effective treatment for ovarian cancer and
      subsequent peritoneal metastasis. Administration of chemoagents in a targeted
      manner may bring the advantage of higher efficiency and lower drug resistance. In
      the present study, folate receptor (FR)-targeted nano-paclitaxel formulations
      were generated and tested for cytotoxicity in a peritoneal xenograft model of
      paclitaxel-resistant ovarian cancer and SKOV3/TAX cell lines. Immunocytochemical
      staining confirmed the expression of FR in both SKOV3 and SKOV3/TAX cells. The
      enrichment of the folic acid-coupled PEGylated nano-paclitaxel liposome (FA-NP)
      in FR-positive cells was visualized with fluorescence. The uptake of the FA-NP
      peaked at 4 h and was more robust than nontargeted PEGylated nano-paclitaxel
      liposome (NP). FA-NP but not NP markedly inhibited the growth of ovarian cancer
      cells and induced a two-fold increase in the doubling time. The cytotoxic effects
      of FA-NP were more potent than NP in both SKOV3 cells [50% of inhibition
      concentration (IC50), 5.67 vs. 50.2 MUg/ml, FA-NP vs. NP] and SKOV3/TAX cells
      (IC50, 0.38 vs. >200 MUg/ml, FA-NP vs. NP). FA-NP caused more G2-M cell cycle
      arrest and apoptotic changes in ovarian cancer cells than NP or regular
      paclitaxel. However, these effects were blunted in the presence of free FA, which
      competitively inhibited the receptor-mediated uptake of FA-NP particles.
      Intraperitoneal (i.p.) administration of FA-NP but not regular paclitaxel, NP, or
      vehicle significantly prolonged the survival and reduced tumor nodule number
      (2.9+/-0.3) in BALB/c nude mice. FA-NP also markedly enhanced the percentage of
      apoptotic cells in peritoneal xenografts of paclitaxel-resistant ovarian cancer
      cells (44.6+/-8.5 vs. 3.2+/-1.1% for vehicle, 22.4+/-5.9% for regular paclitaxel,
      and 35.2+/-7.7% for NP; P<0.05). However, intravenous administration of FA-NP at
      the same dose failed to induce apoptosis (20.1+/-6.2%; P<0.05) and inhibit tumor
      nodule number to the same extent as intraperitoneal administration. FA-NP
      reversed the drug resistance in paclitaxel-resistant SKOV3/TAX ovarian cancer
      cells both in vitro and in vivo. Localized and targeted administration of the FR
      targeted chemoagents might prolong the survival time in patients with drug
      resistant ovarian cancer. 

PMID- 24275315
TI  - N-acetylation of three aromatic amine hair dye precursor molecules eliminates
      their genotoxic potential.
AB  - N-acetylation has been described as a detoxification reaction for aromatic
      amines; however, there is only limited data available showing that this metabolic
      conversion step changes their genotoxicity potential. To extend this database,
      three aromatic amines, all widely used as precursors in oxidative hair dye
      formulations, were chosen for this study: p-phenylenediamine (PPD), 2,5
      diaminotoluene (DAT) and 4-amino-2-hydroxytoluene (AHT). Aiming at a deeper
      mechanistic understanding of the interplay between activation and detoxification
      for this chemical class, we compared the genotoxicity profiles of the parent
      compounds with those of their N-acetylated metabolites. While PPD, DAT and AHT
      all show genotoxic potential in vitro, their N-acetylated metabolites completely
      lack genotoxic potential as shown in the Salmonella typhimurium reversion assay,
      micronucleus test with cultured human lymphocytes (AHT), chromosome aberration
      assay with V79 cells (DAT) and Comet assay performed with V79 cells. For the
      bifunctional aromatic amines studied (PPD and DAT), monoacetylation was
      sufficient to completely abolish their genotoxic potential. Detoxification
      through N-acetylation was further confirmed by comparing PPD, DAT and AHT in the
      Comet assay using standard V79 cells (N-acetyltransferase (NAT) deficient) and
      two NAT-proficient cell lines,V79NAT1*4 and HaCaT (human keratinocytes). Here we
      observed a clear shift of dose-response curves towards decreased genotoxicity of
      the parent aromatic amines in the NAT-proficient cells. These findings suggest
      that genotoxic effects will only be found at concentrations where the N
      acetylation (detoxifying) capacity of the cells is overwhelmed, indicating that a
      'first-pass' effect in skin could be taken into account for risk assessment of
      these topically applied aromatic amines. The findings also indicate that the use
      of liver S-9 preparations, which generally underestimate Phase II reactions,
      contributes to the generation of irrelevant positive results in standard
      genotoxicity tests for this chemical class. 

PMID- 24275316
TI  - Influence of experimental pain on the perception of action capabilities and
      performance of a maximal single-leg hop.
AB  - Changes in an individual's state-for example, anxiety/chronic pain-can modify the
      perception of action capabilities and physical task requirements. In parallel,
      considerable literature supports altered motor performance during both acute and
      chronic pain. This study aimed to determine the effect of experimental pain on
      perception of action capabilities and performance of a dynamic motor task.
      Performance estimates and actual performance of maximal single-leg hops were
      recorded for both legs in 13 healthy participants before, during, and after an
      episode of acute pain induced by a single bolus injection of hypertonic saline
      into vastus lateralis of 1 leg, with the side counterbalanced among participants.
      Both estimation of performance and actual performance were smaller (P < .01)
      during pain than before and after pain. This decrease in estimation and
      performance during pain was apparent for hops using either leg, but it was
      greater (P < .01) for the painful leg (-10.8 +/- 12.1 cm) than for the control
      leg (-5.5 +/- 7.9 cm). Participants accurately estimated their performance in all
      conditions for both legs. The results provide evidence that healthy participants
      have the ability to update the action-scaled relationship between perception and
      ability during acute pain. PERSPECTIVE: This study demonstrates that the
      relationship between perceived physical ability and actual performance is
      effectively updated during acute muscle pain. This match between perceived
      ability and performance could be relevant during clinical pain assessment, with
      the potential to be a biomarker of transition from acute to chronic pain state.

PMID- 24275317
TI  - Health care professionals' reactions to patient pain: impact of knowledge about
      medical evidence and psychosocial influences.
AB  - This study examined the impact of evidence concerning the presence of 1) a
      biomedical basis for pain and 2) psychosocial influences on practitioner
      appraisals of patient pain experiences. Furthermore, the potential moderating
      role of patient pain behavior was examined. In an online study, 52 general
      practitioners and 46 physiotherapists viewed video sequences of 4 patients
      manifesting pain, with accompanying vignettes describing presence or absence of
      medical evidence and psychosocial influences. Participants estimated pain
      intensity, daily interference, sympathy felt, effectiveness of pain medication,
      self-efficacy, their likability, and suspicions of deception. Primary findings
      indicated lower perceived pain and daily interference, less sympathy, lower
      expectations of medication impact, and less self-efficacy when medical evidence
      was absent. The same results were found when psychosocial influences were
      present, but only when the patient displayed higher levels of pain behavior.
      Furthermore, absence of medical evidence was related to less positive evaluations
      of the patients and to higher beliefs in deception in both professions. The
      presence of psychosocial influences was related to less positive evaluations and
      higher beliefs in deception in both professions. In sum, a range of contextual
      factors influence health care practitioner responses to patient pain.
      Implications for caregiving behavior are discussed. PERSPECTIVE: The present
      study indicates that in the absence of clear medical evidence and in the presence
      of psychosocial influences, patient pain might be taken less seriously by health
      care practitioners. These findings are important to further understand the
      difficulties that relate to the clinical encounter between pain patients and
      health care practitioners.

PMID- 24275319
TI  - [Menopause-related symptoms in middle-aged women residing in the Zaragoza
      Province].
AB  - OBJETIVE: The aim of this study was to assess menopausal symptoms and related
      sociodemographic conditions in middle-aged women from the Spanish province of
      Zaragoza. METHOD: This was a cross-sectional study in which 241 women (40-59
      years old) from the Zaragoza province completed the Menopause Rating Scale (MRS)
      and a sociodemographic questionnaire containing personal and partner data to
      assess symptoms associated with the menopause. RESULTS: The most prevalent
      symptoms were musculoskeletal, followed by hot flushes and perspiration. Somatic,
      psychological and urogenital symptoms were more severe in post-menopausal women.
      Somatic and urogenital symptoms worsen with age, body mass index, age at
      menopause, and partner age. Multiple linear regression analysis (MA) for somatic
      symptoms was related with the menopausal status, psychiatric treatment, problems
      with sexual relationships, and history of gender violence. The MA for
      psychological symptoms was associated with menopausal status, psychiatric
      treatment and a history of gender violence. The MA for urogenital symptoms was
      associated with menopausal status, problems with sexual relationships, urinary
      incontinence and partner alcohol abuse. A history of gender violence was reported
      by 11.6% of the women. CONCLUSION: In this sample of middle-aged women,
      menopausal symptoms were related to menopausal status, and other factors
      associated with their partner factors, including gender violence.

PMID- 24275318
TI  - Contralateral prophylactic mastectomy in an Asian population: a single
      institution review.
AB  - BACKGROUND: Contralateral prophylactic mastectomy (CPM) removes the non-diseased
      breast in women who have unilateral breast cancer. This reduces the incidence of
      contralateral breast cancer, and potentially improves survival in high risk
      patients. Such surgical risk-reduction strategy is increasingly being adopted in
      the United States, despite a decreasing incidence of contralateral breast cancer.
      The use of CPM in an Asian population is yet unknown. We present the first Asian
      report on CPM rates and trends in Singapore, the country with the highest
      incidence of breast cancer in Asia. METHODS: A retrospective review of all
      patients who had breast cancer surgery from 2001 to 2010 at the largest
      healthcare system in Singapore was performed. Patient demographics and tumour
      characteristics were analysed with regards to type of surgery performed. Factors
      associated with CPM were identified. RESULTS: From 2001 to 2010, a total of 5130
      patients underwent oncological breast surgery. A decreasing trend of mastectomies
      (82.7%-70.8%), an upward trend of breast conserving surgery (BCS) (17.3%-29.2%)
      and an increasing trend in CPM (0.46%-1.25%) is observed. Patients who opted for
      CPM are likely to be younger (48.4 +/- 9.4 years), married (60%), parous (56.7%),
      with no family history of breast/ovarian cancer (66.7%), and diagnosed at an
      earlier stage. The rate of synchronous occult breast malignancy was found to be
      10% (n = 30), and these were in patients who were of a low cancer-risk profile.
      CONCLUSIONS: This retrospective study reflects an increasing incidence of breast
      cancer in Singapore, with a decrease in mastectomies, and an increase in BCS and
      CPM rates, similar to Western data. Similar to Western populations, the Asian
      woman who opts for CPM is likely to be young and have an earlier stage of breast
      cancer. In contrast, the Asian woman is likely to have no family history of
      breast or ovarian cancers. Commonly cited reasons for increased CPM rates such as
      the increased availability of genetic counselling and pre-operative MRI
      evaluation, along with wide use of reconstruction, do not feature as dominant
      factors in our population, suggesting that the Asian patients may have different
      considerations when electing for CPM.

PMID- 24275320
TI  - Nucleus accumbens core lesions enhance two-way active avoidance.
AB  - The majority of work examining the nucleus accumbens core (NAc) has focused on
      functions pertaining to behaviors guided by appetitive outcomes. These studies
      have pointed to the NAc as being critical for motivating behavior toward
      desirable outcomes. For example, we have recently shown that lesions of the NAc
      impaired performance on a reward-guided decision-making task that required rats
      to choose between differently valued rewards. Unfortunately, much less is known
      about the role that the NAc plays in motivating behavior when aversive outcomes
      are predicted. To address this issue we asked if NAc lesions impact performance
      on a two-way active avoidance task in which rats must learn to shuttle back and
      forth in a behavioral training box in order to avoid a footshock predicted by an
      auditory tone. Although bilateral NAc lesions initially impaired reward-guided
      decision-making, we found that the same lesions improved acquisition and
      retention of two-way active avoidance. 

PMID- 24275321
TI  - Mechanisms regulating the development of oligodendrocytes and central nervous
      system myelin.
AB  - Oligodendrocytes and the myelin they produce are a remarkable vertebrate
      specialization that enables rapid and efficient nerve conduction within the
      central nervous system. The generation of myelin during development involves a
      finely-tuned pathway of oligodendrocyte precursor specification, proliferation
      and migration followed by differentiation and the subsequent myelination of
      appropriate axons. In this review we summarize the molecular mechanisms known to
      regulate each of these processes, including the extracellular ligands that
      promote or inhibit development of the oligodendrocyte lineage, the intracellular
      pathways they signal through and the key transcription factors that mediate their
      effects. Many of these regulatory mechanisms have recurring roles in regulating
      several transitions during oligodendrocyte development, highlighting their
      importance. It is also highly likely that many of these developmental mechanisms
      will also be involved in myelin repair in human neurological disease. 

PMID- 24275322
TI  - The mitochondria as a target for cardioprotection in acute myocardial ischemia.
AB  - The ischemic heart suffers from nutrient deprivation, lack of oxygen, metabolic
      acidosis, hyperkalemia and Ca(2+) overload as well as high level of reactive
      oxygen species (ROS) generation; these risk factors endanger the cardiomyoctes
      and may cause their demise. Nevertheless, the treatment of acute myocardial
      infarction includes reperfusion, although it can exacerbate the effects of
      ischemia since resumption of blood supply to the ischemic myocardium is
      associated with increased ROS production. In the past 20 years, preconditioning
      and postconditioning were revealed, directing research efforts at finding
      pharmacological agents that can mimic these techniques. Soon thereafter, the
      involvement of several molecular pathways such as the reperfusion injury salvage
      kinase, the ATP-sensitive K(+) channel, the survivor-activating factor
      enhancement and the adenosine mono phosphate activated protein kinase pathways
      were discovered. Further, studies have shown that these pathways convey the
      adverse effects of ischemia, reperfusion and the combination thereof to the
      mitochondria, suggesting that the death signals during ischemia and reperfusion
      are controllable, and can therefore be partially inhibited or even reversed.
      Hence, the aim of this review is to describe these signaling pathways, the
      established pre-clinical means to manipulate them, and their current application
      status in the clinic.

PMID- 24275323
TI  - The cardioprotective effects of mineralocorticoid receptor antagonists.
AB  - Despite state-of-the-art reperfusion therapy, morbidity and mortality remain
      significant in patients with an acute myocardial infarction. Therefore, novel
      strategies to limit myocardial ischemia-reperfusion injury are urgently needed.
      Mineralocorticoid receptor (MR) antagonists are attractive candidates for this
      purpose, since several clinical trials in patients with heart failure have
      reported a survival benefit with MR antagonist treatment. MRs are expressed by
      several cells of the cardiovascular system, including cardiomyocytes, cardiac
      fibroblasts, vascular smooth muscle cells, and endothelial cells. Experiments in
      animal models of myocardial infarction have demonstrated that acute
      administration of MR antagonists, either before ischemia or immediately at the
      moment of coronary reperfusion, limits infarct size. This action appears to be
      independent of the presence of aldosterone and cortisol, which are the endogenous
      ligands for the MR. The cardioprotective effect is mediated by a nongenomic
      intracellular signaling pathway, including adenosine receptor stimulation, and
      activation of several components of the Reperfusion Injury Salvage Kinase (RISK)
      pathway. In addition to limiting infarct size, MR antagonists can improve scar
      healing when administered shortly after reperfusion and can reduce cardiac
      remodeling post myocardial infarction. Clinical trials are currently being
      performed studying whether early administration of MR antagonists can indeed
      improve prognosis in patients with an acute myocardial infarction, independent of
      the presence of heart failure. 

PMID- 24275324
TI  - ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic
      differentiation of muscle stem cells.
AB  - Satellite cells are resident stem cells of skeletal muscle, supplying myoblasts
      for post-natal muscle growth, hypertrophy and repair. Many regulatory networks
      control satellite cell function, which includes EGF signalling via the ErbB
      family of receptors. Here we investigated the role of ErbB3 binding protein-1
      (Ebp1) in regulation of myogenic stem cell proliferation and differentiation.
      Ebp1 is a well-conserved DNA/RNA binding protein that is implicated in cell
      growth, apoptosis and differentiation in many cell types. Of the two main Ebp1
      isoforms, only p48 was expressed in satellite cells and C2C12 myoblasts. Although
      not present in quiescent satellite cells, p48 was strongly induced during
      activation, remaining at high levels during proliferation and differentiation.
      While retroviral-mediated over-expression of Ebp1 had only minor effects, siRNA
      mediated Ebp1 knockdown inhibited both proliferation and differentiation of
      satellite cells and C2C12 myoblasts, with a clear failure of myotube formation.
      Ebp1-knockdown significantly reduced ErbB3 receptor levels, yet over-expression
      of ErbB3 in Ebp1 knockdown cells did not rescue differentiation. Ebp1 was also
      expressed by muscle cells during developmental myogenesis in mouse. Since Ebp1 is
      well-conserved between mouse and chick, we switched to chick to examine its role
      in muscle formation. In chick embryo, Ebp1 was expressed in the dermomyotome, and
      myogenic differentiation of muscle progenitors was inhibited by specific Ebp1
      down-regulation using shRNA electroporation. These observations demonstrate a
      conserved function of Ebp1 in the regulation of embryonic muscle progenitors and
      adult muscle stem cells, which likely operates independently of ErbB3 signaling. 

PMID- 24275325
TI  - Patterns of hospice care among military veterans and non-veterans.
AB  - CONTEXT: Historically, hospice use by veterans has lagged behind that of non
      veterans. Little is known about hospice use by veterans at a population level.
      OBJECTIVES: To determine whether veteran and non-veteran hospice users differ by
      demographics, primary diagnosis, location of care, and service utilization.
      METHODS: Using the 2007 National Home and Hospice Care Survey, we identified 483
      veteran and 932 non-veteran male hospice users representing 287,620 hospice
      enrollees nationally. We used chi-square and t-tests to compare veterans and non
      veterans by demographic characteristics, primary diagnosis, and location of
      hospice care. We used multivariate regression to assess for differences in
      hospice diagnosis and location of care, adjusting for demographic and clinical
      factors. We also compared length of stay and number of visits by hospice
      personnel between veterans and non-veterans using multivariate regression.
      RESULTS: Veteran hospice users were older than non-veterans (77.0 vs. 74.3 years,
      P = 0.02) but did not differ by other demographics. In adjusted analyses, cancer
      was a more common primary diagnosis among veterans than non-veterans (56.4% vs.
      48.4%; P = 0.02), and veteran hospice users were more likely than non-veterans to
      receive hospice at home (68.4% vs. 57.6%; P = 0.007). The median adjusted length
      of stay and number of nurse or social worker visits did not differ by veteran
      status (all P > 0.10), but veterans received fewer home health aide visits than
      non-veterans (one every 5.3 days vs. one every 3.7 days; P = 0.002). CONCLUSION:
      Although veteran and non-veteran hospice users were similar on most demographic
      measures, important differences in hospice referral patterns and utilization
      exist.

PMID- 24275326
TI  - Abecedarium: who am I? K'....

PMID- 24275328
TI  - The genetic relationship between handedness and neurodevelopmental disorders.
AB  - Handedness and brain asymmetry have been linked to neurodevelopmental disorders
      such as dyslexia and schizophrenia. The genetic nature of this correlation is not
      understood. Recent discoveries have shown handedness is determined in part by the
      biological pathways that establish left/right (LR) body asymmetry during
      development. Cilia play a key role in this process, and candidate genes for
      dyslexia have also been recently shown to be involved in cilia formation.
      Defective cilia result not only in LR body asymmetry phenotypes but also brain
      midline phenotypes such as an absent corpus callosum. These findings suggest that
      the mechanisms for establishing LR asymmetry in the body are reused for brain
      midline development, which in turn influences traits such as handedness and
      reading ability. 

PMID- 24275330
TI  - Humanizing the healthcare experience: the key to improved outcomes.

PMID- 24275329
TI  - A phenotypic analysis shows that eosinophilic esophagitis is a progressive
      fibrostenotic disease.
AB  - BACKGROUND: Phenotypes of eosinophilic esophagitis (EoE) are not well
      characterized. OBJECTIVE: To describe clinical features of patients with EoE with
      predefined phenotypes, determine predictors of these phenotypes, and make
      inferences about the natural history of EoE. DESIGN: Retrospective study.
      SETTING: Tertiary-care center. PATIENTS: Incident EoE cases from 2001 to 2011
      that met consensus diagnostic guidelines. INTERVENTION: Review of records. MAIN
      OUTCOME MEASUREMENTS: Endoscopic phenotypes, including fibrostenotic,
      inflammatory, or mixed. Other groups of clinical characteristics examined
      included atopy, level of esophageal eosinophilia, and age of symptom onset.
      Multinomial logistic regression assessed predictors of phenotype status. RESULTS:
      Of 379 cases of EoE identified, there were no significant phenotypic differences
      by atopic status or level of eosinophilia. Those with the inflammatory phenotype
      were more likely to be younger than those with mixed or fibrostenotic (13 vs 29
      vs 39 years, respectively; P < .001) and less likely to have dysphagia, food
      impaction, and esophageal dilation (P < .001 for all). The mean symptom length
      before diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; P = .02). After
      multivariate analysis, age and dysphagia independently predicted phenotype. The
      odds ratio (OR) for fibrostenosis for each 10-year increase in age was 2.1 (95%
      CI, 1.7-2.7). The OR for dysphagia was 7.0 (95% CI, 2.6-18.6). LIMITATIONS:
      Retrospective, single-center study. CONCLUSION: In this large EoE cohort, the
      likelihood of fibrostenotic disease increased markedly with age. For every 10
      year increase in age, the odds of having a fibrostenotic EoE phenotype more than
      doubled. This association suggests that the natural history of EoE is a
      progression from an inflammatory to a fibrostenotic disease.

PMID- 24275331
TI  - Correspondence between neutron depolarization and higher order magnetic
      susceptibility to investigate ferromagnetic clusters in phase separated systems.
AB  - It is a tough task to distinguish a short-range ferromagnetically correlated
      cluster-glass phase from a canonical spin-glass-like phase in many magnetic oxide
      systems using conventional magnetometry measurements. As a case study, we
      investigate the magnetic ground state of La0.85Sr0.15CoO3, which is often debated
      based on phase separation issues. We report the results of two samples of
      La0.85Sr0.15CoO3 (S-1 and S-2) prepared under different conditions. Neutron
      depolarization, higher harmonic ac susceptibility and magnetic relaxation studies
      were carried out along with conventional magnetometry measurements to
      differentiate subtle changes at the microscopic level. There is no evidence of
      ferromagnetic correlation in the sample S-2 attributed to a spin-glass phase, and
      this is compounded by the lack of existence of a second order component of higher
      harmonic ac susceptibility and neutron depolarization. A magnetic relaxation
      experiment at different temperatures complements the spin glass characteristic in
      S-2. All these signal a sharp variance when we consider the cluster-glass-like
      phase (phase separated) in S-1, especially when prepared from an improper
      chemical synthesis process. This shows that the nonlinear ac susceptibility is a
      viable tool to detect ferromagnetic clusters such as those the neutron
      depolarization study can reveal. 

PMID- 24275332
TI  - Adrenal nodule visualised on adrenal vein catheterisation.

PMID- 24275333
TI  - New onset S wave in pulmonary embolism: revisited (something old and something
      new).
AB  - We report a case of a young man who had a new onset S wave in lead 1 in his ECG
      with typical symptoms of acute onset of dyspoena 2 months after an episode of
      deep vein thrombosis, S wave disappeared 6 days after thrombolysis. We report
      this case as the clinical course was very typical plus we have reviewed the
      literature regarding diagnosis and risk stratification of pulmonary embolism for
      the student, or the casualty medical officer. 

PMID- 24275334
TI  - A colorectal carcinoma imitating a primary ovarian carcinoma in a postpartum
      woman.
AB  - This is a case report of a 33-year-old woman who presented 5 days post-partum
      with abdominal distension, abdominal discomfort, increased bladder pressure and
      fatigue. These symptoms prompted a pelvic ultrasound and CT scan of the chest,
      abdomen and pelvis which showed a large 20 cm left-sided adnexal mass. Following
      this imaging, blood tests revealed elevated tumour markers CA-125 and lactate
      dehydrogenase, resulting in referral to and surgical intervention by the
      gynaecology oncology team. Pathology and immunohistochemistry indicated that the
      tumour was a metastasis from the colon, that prompted for colonoscopy which
      confirmed that the carcinoma was a metastases from the sigmoid. 

PMID- 24275335
TI  - Skin rash from dengue fever.

PMID- 24275336
TI  - Acute cytomegalovirus hepatitis in an immunocompetent host.
AB  - A 52-year-old woman presented with a 1-week history of recurrent fevers and joint
      pains accompanied by abdominal and low back discomfort. She has a history of
      hypoparathyroidism and is on calcium supplements. Physical examination revealed
      fever and tachycardia. The rest of the examination was normal. Laboratory tests
      showed newly increased transaminase activity. Serum bilirubin and prothrombin
      time were normal. She was admitted for evaluation of acute hepatitis. Serology
      for hepatitis A, B, C and HIV were negative. Her serum acetaminophen and alcohol
      were undetected. Abdominal imaging was normal. Cultures were sterile. Additional
      tests for uncommon viral hepatitis included herpes simplex virus, cytomegalovirus
      and Epstein-Barr virus. Liver biopsy revealed non-specific inflammation.
      Subsequently, cytomegalovirus serology showed an IgM positive and negative IgG
      titre. Cytomegalovirus DNA qualitative PCR was also positive. No antiviral
      medication was given. She continued to have intermittent daily fever but reported
      no associated symptoms. She was discharged 9 days after admission in stable
      condition per her request with the advice to follow-up in the clinic in 1 week.
      Her serum hepatic profile returned to normal and she reported no more episodes of
      fever. Repeated titres of cytomegalovirus serology showed seroconversion. 

PMID- 24275337
TI  - True posterior communicating artery aneurysms with or without increased flow
      dynamical stress: report of three cases.

PMID- 24275338
TI  - Successful treatment of negative pressure hydrocephalus using timely titrated
      external ventricular drainage: a case series.
AB  - OBJECTIVE: Negative-pressure hydrocephalus (NegPH) is a rare clinical entity
      characterised by enlarged ventricles and symptoms consistent with increased
      intracranial pressure (ICP) in the setting of negative ICP. Little has been
      published regarding appropriate treatment and outcomes of negative-pressure
      hydrocephalus patients, and no data have been published demonstrating successful
      therapy producing acceptable long-term outcomes. Here we present 8 cases
      successfully treated by titrated external ventricular drainage (TEVD), including
      drainage at negative (subatmospheric) pressure, and subsequent low-pressure
      ventriculoperitoneal shunting. METHODS: A retrospective audit of all cases of
      negative-pressure hydrocephalus occurring at a university teaching hospital
      between 2006 and 2012 was undertaken. The clinical features of these cases,
      results of radiological investigations, treatment, and outcome were drawn from
      the patients' records. RESULTS: Eight cases of NegPH were identified. All
      patients had at least one preceding intracranial procedure (mean number of
      procedures 3.0). All cases were treated using TEVD, titrated to produce between 5
      and 15 mL per hour of CSF drainage, including drainage under subatmospheric
      pressure if this was required to maintain CSF flow. Mean delay from first
      negative ICP to TEVD was 1.8 days. All 8 patients demonstrated clinical
      improvement. TEVD resulted in improvement in Glasgow Coma Scale (mean increase
      4.6, p=0.003), and increases in ICP (mean increase 8.5, p<0.001). Mean length of
      follow-up was 471.8 days. At follow-up, four patients had returned to pre-morbid
      functioning, three had a reduction in functioning attributable to their initial
      presentation (not NegPH), and one had died of unknown cause. Illustrative case
      descriptions are included. CONCLUSIONS: Negative-pressure hydrocephalus is a rare
      but underrecognised syndrome that can be successfully treated by timely external
      ventricular drainage titrated to maintain CSF flow, and subsequent low-pressure
      ventriculoperitoneal shunting.

PMID- 24275339
TI  - Rapamycin together with TGF-beta1, IL-2 and IL-15 induces the generation of
      functional regulatory gammadeltaT cells from human peripheral blood mononuclear
      cells.
AB  - Regulatory gammadeltaT cell (gammadeltaTreg) is a recently reported subset of
      gammadeltaT cells characterized by both expressions of TCRgammadelta and Foxp3,
      with potential immunosuppressive functions. However, the further studies of
      gammadeltaTreg are limited mainly due to its low quantities in vivo and the lack
      of methods to induce gammadeltaTreg largely in vitro. Here we show that rapamycin
      together with TGF-beta1, IL-2 and IL-15 can induce and expand gammadeltaTregs
      derived from human peripheral blood mononuclear cells efficiently in vitro. Thus
      induced gammadeltaTregs express high levels of Foxp3 and CD25, and display
      significant immunosuppressive activities in vitro. 

PMID- 24275340
TI  - Gate dependent Raman spectroscopy of graphene on hexagonal boron nitride.
AB  - Raman spectroscopy, a fast and nondestructive imaging method, can be used to
      monitor the doping level in graphene devices. We fabricated chemical vapor
      deposition (CVD) grown graphene on atomically flat hexagonal boron nitride (hBN)
      flakes and SiO2 substrates. We compared their Raman response as a function of
      charge carrier density using an ion gel as a top gate. The G peak position, the
      2D peak position, the 2D peak width and the ratio of the 2D peak area to the G
      peak area show a dependence on carrier density that differs for hBN compared to
      SiO2. Histograms of two-dimensional mapping are used to compare the fluctuations
      in the Raman peak properties between the two substrates. The hBN substrate has
      been found to produce fewer fluctuations at the same charge density owing to its
      atomically flat surface and reduced charged impurities. 

PMID- 24275342
TI  - Halomonas desiderata as a bacterial model to predict the possible biological
      nitrate reduction in concrete cells of nuclear waste disposals.
AB  - After closure of a waste disposal cell in a repository for radioactive waste,
      resaturation is likely to cause the release of soluble species contained in
      cement and bituminous matrices, such as ionic species (nitrates, sulfates,
      calcium and alkaline ions, etc.), organic matter (mainly organic acids), or gases
      (from steel containers and reinforced concrete structures as well as from
      radiolysis within the waste packages). However, in the presence of nitrates in
      the near-field of waste, the waste cell can initiate oxidative conditions leading
      to enhanced mobility of redox-sensitive radionuclides (RN). In biotic conditions
      and in the presence of organic matter and/or hydrogen as electron donors,
      nitrates may be microbiologically reduced, allowing a return to reducing
      conditions that promote the safety of storage. Our work aims to analyze the
      possible microbial reactivity of nitrates at the bitumen - concrete interface in
      conditions as close as possible to radioactive waste storage conditions in order
      (i) to evaluate the nitrate reaction kinetics; (ii) to identify the by-products
      (NO2(-), NH4(+), N2, N2O, etc.); and (iii) to discriminate between the roles of
      planktonic bacteria and those adhering as a biofilm structure in the denitrifying
      activity. Leaching experiments on solid matrices (bitumen and cement pastes) were
      first implemented to define the physicochemical conditions that microorganisms
      are likely to meet at the bitumen-concrete interface, e.g. highly alkaline pH
      conditions (10 < pH < 11) imposed by the cement matrix. The screening of a range
      of anaerobic denitrifying bacterial strains led us to select Halomonas desiderata
      as a model bacterium capable of catalyzing the reaction of nitrate reduction in
      these particular conditions of pH. The denitrifying activity of H. desiderata was
      quantified in a batch bioreactor in the presence of solid matrices and/or
      leachate from bitumen and cement matrices. Denitrification was relatively fast in
      the presence of cement matrix (<100 h) and 2-3 times slower in the presence of
      bituminous matrix (pH 9.7). The maximal rate of denitrification was approximately
      0.063 mM h(-1) and some traces of nitrite were detected for a few hours (<2%).
      Overall, the presence of solid cement promoted the kinetics of denitrification.
      The inspection of the solid surfaces at the end of the experiment revealed the
      presence of a biofilm of H. desiderata on the cement paste surface. These
      attached bacteria showed a comparable denitrifying activity to planktonic
      bacterial culture. However, no colonization of bitumen was observed either by SEM
      or by epifluorescence microscopy.

PMID- 24275341
TI  - Chutes and ladders in hepatitis C nucleoside drug development.
AB  - Chutes and Ladders is an exciting up-and-down-again game in which players race to
      be the first to the top of the board. Along the way, they will find ladders to
      help them advance, and chutes that will cause them to move backwards. The
      development of nucleoside analogs for clinical treatment of hepatitis C presents
      a similar scenario in which taking shortcuts may help quickly advance a program,
      but there is always a tremendous risk of being sent backwards as one competes for
      the finish line. In recent years the treatment options for chronic hepatitis C
      virus (HCV) infection have expand due to the development of a replicon based in
      vitro evaluation system, allowing for the identification of multiple drugable
      viral targets along with a concerted and substantial drug discovery effort. Three
      major drug targets have reached clinical study for chronic HCV infection: the
      NS3/4A serine protease, the large phosphoprotein NS5A, and the NS5B RNA-dependent
      RNA polymerase. Recently, two oral HCV protease inhibitors were approved by the
      FDA and were the first direct acting anti-HCV agents to result from the
      substantial research in this area. There are currently many new chemical entities
      from several different target classes that are being evaluated worldwide in
      clinical trials for their effectiveness at achieving a sustained virologic
      response (SVR) (Pham et al., 2004; Radkowski et al., 2005). Clearly the goal is
      to develop therapies leading to a cure that are safe, widely accessible and
      available, and effective against all HCV genotypes (GT), and all stages of the
      disease. Nucleoside analogs that target the HCV NS5B polymerase that have reached
      human clinical trials is the focus of this review as they have demonstrated
      significant advantages in the clinic with broader activity against the various
      HCV GT and a higher barrier to the development of resistant viruses when compared
      to all other classes of HCV inhibitors. 

PMID- 24275343
TI  - Update on biomarkers of hepatocellular carcinoma.
AB  - New biomarkers of hepatocellular carcinoma (HCC) have been identified using
      advanced genomic, proteomic, and metabolomics technologies. These are being
      developed not only for use in diagnosis of HCC, but also in prediction of patient
      and treatment outcomes and individualization of therapy. Some HCC biomarkers are
      currently used in surveillance to detect early stage HCCs and reduce mortality.
      Further studies are needed to determine whether the recently identified HCC
      biomarkers can be used in clinical practice; most are only in phase 1 or 2
      studies. The diagnostic and predictive abilities of biomarkers are limited by the
      heterogeneous nature of HCCs; there is no perfect single biomarker of this tumor.
      To improve performance, combinations of biomarkers (panels), or combinations of
      biomarkers and clinical parameters or laboratory test results, might be required.
      We describe recently discovered biomarkers of HCC and discuss challenges to their
      development and application. 

PMID- 24275344
TI  - Role of familiarity versus interleukin-1 genes cluster polymorphisms in chronic
      periodontitis.
AB  - Periodontitis (PO) is a multifactorial disease affecting about 10% to 20% of the
      general population. Several studies have suggested that part of the clinical
      variability in PO might be explained by genetic factors. Among the candidate
      genes for PO, IL1 gene polymorphisms have been broadly investigated, with
      variable results, for their relationship with the disease. We studied three IL1
      polymorphisms, IL1A C[-889]T (rs1800587), IL1B C[3953/4]T (rs1143634), and IL1RN
      VNTR [+2018] (rs419598) in relation to different life styles and familiarities.
      We did not find correlation between these IL1 polymorphisms and chronic PO, as
      well as between chronic PO and life styles (smoking, alcohol, coffee, fizzy drink
      and fish). We found a strong correlation, also after adjustment for age, between
      familiarity and PO onset (P=0.0062; OR 5.754, 95% CI 1.644-20.145). In
      conclusion, we did confirm the previously suggested association between PO and
      IL1 gene cluster polymorphisms, and between PO and four common risk factors
      (coffee, smoking, alcohol and fizzy drinks) and one common protective factor
      (fish). On the contrary, we found a strong role of familiarity. 

PMID- 24275345
TI  - Expression profiling of the sex-related gene Dmrt1 in adults of the Lusitanian
      toadfish Halobatrachus didactylus (Bloch and Schneider, 1801).
AB  - Doublesex and mab-3 related transcription factor 1 (Dmrt1) gene is a widely
      conserved gene involved in sex determination and differentiation across phyla. To
      gain insights on Dmrt1 implication for fish gonad cell differentiation and
      gametogenesis development, its mRNA was isolated from testis and ovary from the
      Lusitanian toadfish (Halobatrachus didactylus). The cDNA from Dmrt1 was
      synthesized and cloned, whereas its quantitative and qualitative gene expression,
      as well as its protein immunolocalization, were analyzed. A main product of 1.38
      kb, which encodes a protein of 295 aa, was reported, but other minority Dmrt1
      products were also identified by RACE-PCR. This gene is predominantly expressed
      in testis (about 20 times more than in other organs or tissues), specially in
      spermatogonia, spermatocytes and spermatids, as well as in somatic Sertoli cells,
      indicating that Dmrt1 plays an important role in spermatogenesis. Although Dmrt1
      transcripts also seem to be involved in oogenesis development, and it cannot be
      excluded that toadfish Dmrt1 could be functionally involved in other processes
      not related to sex.

PMID- 24275346
TI  - Characterization of regulatory mechanism of Poncirus trifoliata microRNAs on
      their target genes with an integrated strategy of newly developed PPM-RACE and
      RLM-RACE.
AB  - MicroRNAs (miRNAs) play an important role in post-transcriptional gene regulation
      that involved various biological and metabolic processes. Many extensive studies
      have been done in model plant species, to discover miRNAs' regulating expression
      of their target genes and analyze their functions. But, the function of Poncirus
      trifoliata miRNAs has not been properly investigated. In this study, we employed
      the RNA ligase-mediated 5' rapid amplification of cDNA ends (RLM-RACE) and the
      newly developed method called poly (A) polymerase-mediated 3' rapid amplification
      of cDNA ends (PPM-RACE), which mapped the cleavage site of target mRNAs and
      detected expression patterns of cleaved fragments that could in turn indicate the
      regulatory functions of the miRNAs on their target genes. Furthermore, the
      spatiotemporal expression levels of target genes were analyzed by qRT-PCR, with
      exhibiting different expression trends from their corresponding miRNAs, thus
      indicating the cleavage mode of miRNAs on their target genes. The expression
      patterns of miRNAs, their target mRNAs and cleaved target mRNAs in different
      organs of juvenile and adult trifoliate orange were studied. The results showed
      that the expression of miRNAs and their target mRNAs was in a trade-off trend.
      When the miRNA expression was high, its corresponding target mRNA expression was
      low, while the cleaved target mRNA expression was high; when the miRNA expression
      was low, its target mRNA expression was high, while the expression of cleaved
      target mRNAs follows that of the miRNA. The validation of the cleavage site of
      target mRNAs and the detection of expression patterns of cleaved fragments can
      further broaden the knowledge of small RNA-mediated regulation in P. trifoliate. 

PMID- 24275347
TI  - Impact resistance and fractography in ultra high molecular weight polyethylenes.
AB  - Highly crosslinked ultra high molecular weight polyethylenes (UHMWPE) stabilized
      by a remelting process or by the addition of an antioxidant are highly wear
      resistant and chemically stable. However, these polyethylenes currently used in
      total joint replacements suffer a loss of mechanical properties, especially in
      terms of fracture toughness. In this study we analyze the impact behavior of
      different polyethylenes using an instrumented double notch Izod test. The
      materials studied are three resins: GUR1050, GUR1020 with 0.1wt% of vitamin E,
      and MG003 with 0.1wt% of vitamin E. These resins were gamma irradiated at 90kGy,
      and pre and post-irradiation remelting processes were applied to GUR1050 for two
      different time periods. Microstructural data were determined by means of
      differential scanning calorimetry and transmission electron microscopy.
      Fractography carried out on the impact fracture surfaces and images obtained by
      scanning electron microscopy after etching indicated the existence of a fringe
      structure formed by consecutive ductile-brittle and brittle-ductile transitions,
      which is related to the appearance of discontinuities in the load-deflection
      curves. A correlation has been made of the macroscopic impact strength results
      and the molecular chain and microstructural characteristics of these
      aforementioned materials, with a view to designing future resins with improved
      impact resistance. The use of UHMWPE resins with low molecular weight or the
      application of a remelting treatment could contribute to obtain a better impact
      strength behavior. 

PMID- 24275348
TI  - Optimization of potency and pharmacokinetics of tricyclic indole derived
      inhibitors of HCV NS5B polymerase. Identification of ester prodrugs with improved
      oral pharmacokinetics.
AB  - HCV infections are the leading causes for hepatocellular carcinoma and liver
      transplantation in the United States. Recent advances in drug discovery have
      identified direct acting antivirals which have significantly improved cure rates
      in patients. Current efforts are directed towards identification of novel direct
      acting antiviral targeting different mechanism of actions which could become part
      of all oral therapies. We recently disclosed the identification of a novel
      tricyclic indole derived inhibitors of HCV NS5B polymerase that bound to the
      enzyme close to the active site. In this manuscript we describe further
      optimization of potency and pharmacokinetics (PK) of these inhibitors to identify
      compounds in low nM potency against gt-1b. These analogs also demonstrate
      excellent PK in rats and monkeys when administered as a dimethyl ethyl amino
      ester prodrug. 

PMID- 24275349
TI  - Design, synthesis and preliminary SAR studies of novel N-arylmethyl substituted
      piperidine-linked aniline derivatives as potent HIV-1 NNRTIs.
AB  - A series of novel N-arylmethyl substituted piperidine-linked aniline derivatives
      were designed, synthesized and evaluated for their anti-HIV activity in MT-4
      cells. All the new compounds showed moderate to potent activities against wild
      type (wt) HIV-1 with an EC50 range from 0.022 to 2.1 MUM. Among them, compound
      5a6 (EC50=0.022 +/- 0.0091 MUM, SI >10,770) was confirmed to be the most potent
      and selective inhibitor, which proved more potent than DDI and DLV in a cell
      based assay against wt HIV-1, and more efficient than NVP in an RT (reverse
      transcriptase) assay. Besides, it is worth noting that compound 7a1 retained
      moderate inhibitory activity (EC50=4.8 +/- 0.95 MUM) against the HIV-1 double RT
      mutant strain (K103N/Y181C). The preliminary structure-activity relationship was
      discussed and rationalized by molecular simulation.

PMID- 24275350
TI  - The phytoalexins brassilexin and camalexin inhibit cyclobrassinin hydrolase, a
      unique enzyme from the fungal pathogen Alternaria brassicicola.
AB  - Alternaria brassicicola is a fungal pathogen of many agriculturally important
      cruciferous crops. Cyclobrassinin hydrolase (CH) is an enzyme produced by A.
      brassicicola that catalyzes the transformation of the cruciferous phytoalexin
      cyclobrassinin into S-methyl[(2-sulfanyl-1H-indolyl-3)methyl]carbamothioate. The
      purification and characterization of CH was performed using a four-step
      chromatography method. SDS-PAGE and gel exclusion chromatography indicated that
      CH is a tetrameric protein with molecular mass of 330 kDa. Sequence analysis and
      chemical modification of CH with selective reagents suggested that the enzyme
      mediates hydrolysis of cyclobrassinin using a catalytic amino acid triad. Enzyme
      kinetic studies using cyclobrassinin and 1-methylcyclobrassinin as substrates
      revealed that CH displayed positive substrate cooperativity. Investigation of the
      effect of nine phytoalexins and two derivatives on the activity of CH indicated
      that six compounds displayed inhibitory activity: brassilexin, 1
      methylbrassilexin, dioxibrassinin, camalexin, brassicanal A and sinalexin. The
      enzyme kinetics of CH strongly suggested that brassilexin and 1-methylbrassilexin
      are noncompetitive inhibitors of CH activity, and that camalexin is a competitive
      inhibitor while dioxibrassinin inhibits CH through a mixed mechanism. The
      phytoalexin brassilexin is the most effective inhibitor of CH (K(i)=32 +/- 9
      MUM). These results suggest that crops able to accumulate higher concentration of
      brassilexin would display higher resistance levels to the fungus.

PMID- 24275351
TI  - Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase
      cerebral vascular mitochondrial biogenesis and reactive oxygen species
      protection.
AB  - We previously found that estrogen exerts a novel protective effect on
      mitochondria in brain vasculature. Here we demonstrate in rat cerebral blood
      vessels that 17beta-estradiol (estrogen), both in vivo and ex vivo, affects key
      transcriptional coactivators responsible for mitochondrial regulation. Treatment
      of ovariectomized rats with estrogen in vivo lowered mRNA levels of peroxisome
      proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) but
      increased levels of the other PGC-1 isoforms: PGC-1beta and PGC-1 related
      coactivator (PRC). In vessels ex vivo, estrogen decreased protein levels of PGC
      1alpha via activation of phosphatidylinositol 3-kinase (PI3K). Estrogen treatment
      also increased phosphorylation of forkhead transcription factor, FoxO1, a known
      pathway for PGC-1alpha downregulation. In contrast to the decrease in PGC-1alpha,
      estrogen increased protein levels of nuclear respiratory factor 1, a known PGC
      target and mediator of mitochondrial biogenesis. The latter effect of estrogen
      was independent of PI3K, suggesting a separate mechanism consistent with
      increased expression of PGC-1beta and PRC. We demonstrated increased
      mitochondrial biogenesis following estrogen treatment in vivo; cerebrovascular
      levels of mitochondrial transcription factor A and electron transport chain
      subunits as well as the mitochondrial/nuclear DNA ratio were increased. We
      examined a downstream target of PGC-1beta, glutamate-cysteine ligase (GCL), the
      rate-limiting enzyme for glutathione synthesis. In vivo estrogen increased
      protein levels of both GCL subunits and total glutathione levels. Together these
      data show estrogen differentially regulates PGC-1 isoforms in brain vasculature,
      underscoring the importance of these coactivators in adapting mitochondria in
      specific tissues. By upregulating PGC-1beta and/or PRC, estrogen appears to
      enhance mitochondrial biogenesis, function and reactive oxygen species
      protection. 

PMID- 24275352
TI  - Myogenic effect of SP-1f and SP-1h two novel beta3-adrenoceptor (beta3-AR)
      agonists in human colonic circular smooth muscle.
AB  - The effect of two novel beta3-adrenoceptor (beta3-AR) agonists SP-1f and SP-1h on
      human colon circular smooth muscle contractility and beta3-AR mRNA expression
      have been determined. beta3-AR is ascertained co-participates to the control of
      the gut motility. Isometric tension on human colon muscle strips was measured in
      response to increasing concentrations of SP-1f, SP-1h and (-)-isoprenaline, alone
      and in the presence of Betaxolol, ICI 11,855 and SR 59230A (beta1-, beta2- and
      beta3-AR antagonists, respectively). (-)-Isoprenaline concentration-dependently
      relaxed circular muscle strips with an EC50=0.32+/-0.06MUM. Such an effect was
      antagonized either by the contemporaneously presence of Betaxolol and ICI 11,855
      [(-)-isoprenaline EC50=1.75+/-0.35MUM, pKB=7.88+/-0.10] or by Betaxolol, ICI
      11,855 and SR 59230A [(-)-isoprenaline EC50=3.49+/-0.38MUM, pKB=8.51+/-0.14].
      Besides, SP-1f and SP-1h concentration-dependently relaxed circular muscle strips
      with an EC50=0.35+/-0.07MUM and 0.45+/-0.12MUM, respectively. These values
      remained unchanged by blocking the beta1- and beta2-AR. The presence of SR 59230A
      antagonized the relaxing effect of SP-1f (EC50=3.51+/-0.94MUM, pKB=8.93+/-0.16)
      and did not modify the SP-1h relaxing potency. In colon circular smooth muscle
      and in mucosa, beta3-AR mRNA expression levels were found to be 0.39+/-0.70 and
      0.26+/-0.12 (P<0.05), respectively. Such results provide further evidence of the
      beta3-adrenoceptor functional role in the human colon and the crucial
      contribution of SP-1f to the control of the gut dysmotility. 

PMID- 24275353
TI  - Inhibitory effects of beta-amyloid on the nicotinic receptors which stimulate
      glutamate release in rat hippocampus: the glial contribution.
AB  - We investigated on the neuronal nicotinic acetylcholine receptor subtypes
      involved in the cholinergic control of in vivo hippocampal glutamate (GLU),
      aspartate (ASP) and inhibitory gamma-aminobutyric acid (GABA) overflow. We also
      investigated on the possible contribution of nicotinic acetylcholine receptors
      subtypes present on astrocytes in the regulation of the three neurotransmitter
      amino acids overflow using hippocampal gliosomes and on the effects of beta
      amyloid (Abeta) 1-40 on the nicotinic control of amino acid neurotransmitter
      release. Nicotine was able to enhance the in vivo overflow of the three amino
      acids being more potent in stimulating GLU overflow. The alpha7 selective agonist
      PHA543613 induced an overflow very similar to that of nicotine. The alpha4beta2
      selective agonist 5IA85380 was significantly less potent in inducing GLU overflow
      while the overflow of ASP and GABA were almost inconsistent. Abeta1-40 inhibited
      the neurotransmitter overflow stimulated by PHA543613 but not the one evoked by
      5IA85380. In hippocampal gliosomes nicotine elicited selectively GLU overflow
      which was also evoked by 5IA85380 and by the alpha7 selective agonist choline.
      Nicotine- and choline-induced glutamate overflow in gliosomes was inhibited by
      Aalpha1-40. In conclusion nicotine administration in vivo elicits hippocampal GLU
      release mostly through alpha7 nicotinic acetylcholine receptors likely present
      both on neurons and astrocytes. Abeta inhibitory effect on the nicotinic-control
      of GLU release seems to depend primarily to the inhibition of alpha7 nicotinic
      acetylcholine receptors functional responses. 

PMID- 24275354
TI  - Hybrid ameloblastoma and adenomatoid odontogenic tumor: report of a case and
      review of hybrid variations in the literature.
AB  - Hybrid odontogenic tumors including 2 or more different histologic types have
      been documented, but their occurrences are not very common. We present a case of
      hybrid odontogenic tumor composed of ameloblastoma and adenomatoid odontogenic
      tumor (AOT) arising in the mandibular molar region of a 31-year-old Japanese
      woman who had a history of familial adenomatous polyposis. The tumor, measuring
      10 mm in diameter, was surgically removed from the alveolar bone.
      Histopathologically, the tumor consisted of both follicular and plexiform types
      of ameloblastoma in which multiple and smaller foci of AOT were intermingled.
      There have been 3 reported cases of hybrid ameloblastoma and AOT, all of which
      presented unicystic types as ameloblastoma components. This, however, is the
      first report of a hybrid tumor containing an authentic solid-type ameloblastoma
      compartment and an AOT compartment in a patient with a background of familial
      adenomatous polyposis.

PMID- 24275355
TI  - T4 squamous cell carcinoma of the oral tongue without mandibular involvement:
      surgery or chemoradiotherapy?
AB  - OBJECTIVE: To investigate disease control and functional outcomes in patients
      with T4 squamous cell carcinoma of the oral tongue who had undergone surgery or
      definitive chemoradiotherapy. STUDY DESIGN: Records of all consecutive patients
      with T4 squamous cell carcinoma of the oral tongue treated radically between 1999
      and 2010 at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia,
      were retrospectively reviewed. RESULTS: Of 31 patients, 19 underwent surgery and
      12 underwent definitive chemoradiotherapy. There were no significant differences
      between cohorts in terms of age, nodal involvement, or performance status. All
      patients had T4 disease on the basis of extrinsic muscle invasion; none had bone
      invasion. Disease outcomes at 5 years after surgery or chemoradiotherapy were not
      significantly different, including local control (61% vs 70%), progression-free
      rate (56% vs 55%), and overall survival (27% vs 40%). A higher proportion of
      patients in the chemoradiotherapy group had only mild impairment of speech and
      swallowing. CONCLUSIONS: Definitive chemoradiotherapy may be a reasonable
      alternative to surgery for patients with T4 squamous cell carcinoma of the oral
      tongue without bony invasion.

PMID- 24275356
TI  - Pigmented mucoepidermoid carcinoma with spindle cell differentiation.
AB  - Mucoepidermoid carcinoma is the most common malignant salivary gland tumor of
      children and adults, showing diverse histopathologic features. Mucoepidermoid
      carcinoma with both melanin pigmentation and spindle cell differentiation has not
      been previously reported. We report the first documented case of pigmented
      mucoepidermoid carcinoma with spindle cell differentiation in a 34-year-old woman
      who presented with a swelling of the floor of the mouth.

PMID- 24275357
TI  - Predictive factors of distal femoral fracture nonunion after lateral locked
      plating: a retrospective multicenter case-control study of 283 fractures.
AB  - INTRODUCTION: Reported initial success rates after lateral locked plating (LLP)
      of distal femur fractures have led to more concerning outcomes with reported
      nonunion rates now ranging from 0 to 21%. Reported factors associated with
      nonunion include comorbidities such as obesity, age and diabetes. In this study,
      our goal was to identify patient comorbidities, injury and construct
      characteristics that are independent predictors of nonunion risk in LLP of distal
      femur fractures; and to develop a predictive algorithm of nonunion risk,
      irrespective of institutional criteria for clinical intervention variability.
      PATIENTS AND METHODS: A retrospective review of 283 distal femoral fractures in
      278 consecutive patients treated with LLP at three Level1 academic trauma
      centers. Nonunion was liberally defined as need for secondary procedure to manage
      poor healing based on unrestricted surgeon criteria. Patient demographics (age,
      gender), comorbidities (obesity, smoking, diabetes, chronic steroid use,
      dialysis), injury characteristics (AO type, periprosthetic fracture, open
      fracture, infection), and management factors (institution, reason for
      intervention, time to intervention, plate length, screw density, and plate
      material) were obtained for all participants. Multivariable analysis was
      performed using logistic regression to control for confounding in order to
      identify independent risk factors for nonunion. RESULTS: 28 of the 283 fractures
      were treated for nonunion, 13 were referred to us from other institutions.
      Obesity (BMI>30), open fracture, occurrence of infection, and use of stainless
      steel plate were significant independent risk factors (P<0.01). A predictive
      algorithm demonstrates that when none of these variables are present (titanium
      instead of stainless steel) the risk of nonunion requiring intervention is 4%,
      but increases to 96% with all factors present. When a stainless plate is used,
      obesity alone carries a risk of 44% while infection alone a risk of 66%. While
      Chi-square testing suggested no institutional differences in nonunion rates, the
      time to intervention for nonunion varied inversely with nonunion rates between
      institutions, indicating varying trends in management approach. DISCUSSION:
      Obesity, open fracture, occurrence of infection, and the use of stainless steel
      are prognostic risk factors of nonunion in distal femoral fractures treated with
      LLP independent of differing trends in how surgeons intervene in the management
      of nonunion.

PMID- 24275358
TI  - Intramedullary nailing versus plating for extra-articular distal tibial
      metaphyseal fracture: a systematic review and meta-analysis.
AB  - INTRODUCTION: With development in the techniques of reduction and fixation, there
      has been a controversy in comparison between intramedullary nailing (IMN) and
      plating for the treatment of distal tibial metaphyseal fracture (DTF). The study
      aimed to investigate: (1) which fixation, IMN or plating, was better in the
      clinical outcomes and in the complications for the treatment of DTF and (2) which
      modifying variables affected the comparative results between the two modalities.
      METHODS: PubMed, EMBASE, OVID, Scopus, ISI Web of Science, the Cochrane Library,
      Google Scholar and specific orthopaedic journals were searched from inception to
      July 2013, using the search strategy of '('Fracture Fixation, Intramedullary'
      [MeSH]) AND ('Tibial Fractures' [MeSH]) AND (plate OR plating)'. All prospective
      and retrospective controlled trials comparing function, pain, bone union and
      complications between IMN and plating for DTF were identified. Our analysis had
      no limitation of the language or the publication year. The primary outcome
      measurements were complication rate, union time, operation time and hospital
      stays, while the secondary outcome measurements were functional score and pain
      score. RESULT: Fourteen of 6620 studies with 842 patients were included. IMN was
      probably preferential to plating for DTF given its higher functional score
      (p=0.01), lower risk of infection (p=0.02) and comparable pain score (p=0.33),
      total complication rate (p=0.53) and time to union (p=0.86). However, plating had
      a lower malunion rate than IMN (p<0.0001). All the results were based on the
      Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      evidence of moderate quality. CONCLUSIONS: With a satisfying alignment obtained,
      IMN may be preferential to plating for fixation of DTF with better function and
      lower risk of infection. However, IMN showed higher malunion rate for fixation of
      DTF. With the biases in our meta-analysis, it will ultimately require a rigorous
      and adequately powered randomised controlled trial (RCT) to prove. LEVEL OF
      EVIDENCE: Level III, therapeutic study (systematic review).

PMID- 24275359
TI  - A proposal of a spin cell using light on magnetic tunneling junctions.
AB  - We propose and theoretically investigate a spin cell using light as the power
      source. Such a device can be realized when a quantum dot is connected to two
      ferromagnetic electrodes. In the case of identical electrodes, a pure spin
      current (PSC) can be generated when the light is shone on the quantum dot.
      Moreover, the PSC can be tuned continuously from zero to the maximum when the
      magnetic moment orientations of the two electrodes are changed from parallel to
      anti-parallel. The output spin bias is linear with the light power in the low
      power region, while it approaches the theoretical limit when the power is
      extremely high because of the electrodes' renormalization by the spin transfer
      torque. This effect implies that light energy can be transferred to electron spin
      directly, which may be applicable in future opto-spintronics. 

PMID- 24275360
TI  - Hypokalaemic periodic paralysis in rural northern India--most have secondary
      causes.
AB  - Hypokalaemic periodic paralysis (HPP) is a life-threatening condition. Our aim
      was to study the clinical profile and laboratory parameters of HPP patients and
      to develop an algorithm to determine the causes of HPP. 84 patients presented
      with HPP over a 3 year period. 58 (69.0%) were found to have renal tubular
      acidosis (RTA). The other causes were idiopathic HPP (8 (9.5%)), acute
      gastroenteritis (4 (4.8%)), suspected primary hyperaldosteronism and familial HPP
      (2 each (2.4%)) and suspected Gitelman/Bartter Syndrome and thyrotoxic periodic
      paralysis (1 each (1.2%)). The number of cases peaks in the hot season. Over a
      third of the patients (35.7%) had recurrent episodes. 80% had secondary HPP and
      therefore a biochemical evaluation is mandatory. A simple algorithm was
      developed. Both health professionals and patients need further education
      regarding this problem in order to improve diagnosis and treatment and to improve
      compliance. 

PMID- 24275361
TI  - Solution structure of Rv0569, potent hypoxic signal transduction protein, from
      Mycobacterium tuberculosis.
AB  - The latent infection is unique characteristic of Mycobacterium tuberculosis to
      overcome human immune response for its survival. The M. tb develops adaptation to
      extreme stress conditions to increase the viability, thus easily acquires drug
      resistance than any other bacteria and maintains a long-term infection status
      without any symptoms. Rv0569 is a conserved hypothetical protein that
      overexpresses under dormant state induced by hypoxia, starvation, and medication.
      To study function and structure in detail, we determined the solution structure
      of Rv0569 by NMR. NOE and RDC restraints were used to calculate the structure,
      which was further refined with AMBER. Rv0569 is composed of five antiparallel
      beta-sheets and one alpha-helix. Rv0569 shows structural similarity with its
      homolog Rv2302, yet there is a big difference in the orientation of C-terminal
      alpha-helix between Rv0569 and Rv2302. According to previous studies, Rv0569
      might comprise a hypoxia induced operon with the Rv0570 which is located 29 bp
      downstream of the Rv0569 and Rv0570 plays an important role in the latent
      infection. From our structure and bioinformatics research, we suggest that Rv0569
      contributes to signaling transduction in hypoxic condition by binding with DNA
      for upregulation of Rv0570 or supporting Rv0570 for binding ATP during dormancy
      of tuberculosis. 

PMID- 24275362
TI  - 25-Hydroxyvitamin D levels after recovery from tuberculosis: insights into
      pathogenesis.
AB  - OBJECTIVE: 25-Hydroxyvitamin D [25(OH)D] levels after recovery from tuberculosis
      (TB) may reflect pre-morbid levels and therefore provide insight into
      pathogenesis. We assessed 25(OH)D levels after recovery from TB disease, and
      compared to levels in persons without TB disease. METHODS: Case-control study.
      Cases were persons who had recovered from culture-confirmed Mycobacterium
      tuberculosis disease. Controls were persons without TB disease. Total 25(OH)D was
      measured from stored plasma specimens using liquid chromatography-mass
      spectrometry. RESULTS: 29 persons with prior TB disease and 36 controls were
      included. Median 25(OH)D levels were 24.7 ng/mL (IQR, 18.3-34.1) in prior TB
      disease, and 33.6 ng/mL (IQR, 26.2-42.4) in controls (Mann-Whitney; P = 0.01).
      Multivariable linear regression analysis showed that black race (adjusted mean
      difference [beta] = -8.3 ng/mL; 95% CI -14.5, -2.2; P < 0.01), enrollment in
      winter (beta = -10.4 ng/mL; 95% CI -17.0, -3.8; P < 0.01) and prior TB disease
      (beta = -5.8 ng/mL; 95% CI -11.4, -0.3; P = 0.05) were associated with lower
      25(OH)D levels. CONCLUSIONS: Persons who had recovered from TB disease had lower
      25(OH)D levels compared to controls without TB disease, after adjusting for
      important confounders. Larger, longitudinal studies are needed to further
      characterize the possible role of low 25(OH)D in the pathogenesis of TB disease
      and TB recurrence after recovery.

PMID- 24275363
TI  - Regulation of TH17 markers early in life through maternal farm exposure.
AB  - BACKGROUND: Previous studies suggested that maternal farm exposure during
      pregnancy modulates early immune development toward an allergy-protective status
      potentially mediated by TH1 or regulatory T (Treg) cells. However, the underlying
      mechanisms might involve immune modulation of additional T-cell populations, such
      as TH17 cells, influenced by genetic predisposition. OBJECTIVE: We examined the
      role of maternal farm exposure and genetic predisposition on TH17 cell responses
      to innate and adaptive immune stimulation in cord blood. METHODS: Eighty-four
      pregnant mothers were recruited before delivery. Detailed questionnaires (60
      nonfarming mother, 22 farming mothers, and 2 exclusions) assessed farming
      exposures. Cord blood was stimulated with lipid A, peptidoglycan (Ppg), or PHA.
      TH17 lineage (retinoic acid receptor-related orphan receptor C [RORC], retinoic
      acid receptor-related orphan receptor alpha [RORA], IL-23 receptor [IL23R], IL17,
      IL17F, and IL22) and Treg cell markers (forkhead box protein 3 [FOXP3],
      lymphocyte activation gene 3 [LAG3], and glucocorticoid-induced TNF receptor
      [GITR]) were assessed at the mRNA level. TH17/Treg/TH1/TH2 cytokines and 7 single
      nucleotide polymorphisms within the TH17 lineage (RORC, IL23R, and IL17) were
      examined. RESULTS: TH17 lineage mRNA markers were expressed at birth at low
      concentrations independent of maternal farm exposure. A positive correlation
      between TH17 lineage markers and FOXP3 (mRNA) was observed on stimulation
      (nonfarming mothers: lipid A, Ppg, and PHA; farming mothers: Ppg and PHA),
      influenced by maternal farming. Specific single nucleotide polymorphisms within
      the TH17 lineage genes influenced gene expression of TH17 and Treg cell markers
      and cytokine secretion. CONCLUSIONS: Gene expression of TH17 lineage markers in
      cord blood was not influenced by maternal farming. Yet TH17 and Treg cell markers
      were positively correlated and influenced by maternal farm exposure. Our data
      suggest that prenatal exposures and genetic predisposition play a role during
      early TH17 immune maturation, potentially regulating the development of immune
      mediated diseases, such as childhood asthma.

PMID- 24275364
TI  - Fecal leukocyte in the diagnosis of ulcerative colitis.

PMID- 24275365
TI  - Mortality of children following a diagnosis of HIV infection in northeastern
      Brazil.

PMID- 24275366
TI  - Association of X4 tropism with disease progression in antiretroviral-treated
      children and adolescents living with HIV/AIDS in Sao Paulo, Brazil.
AB  - Management of children with HIV/AIDS is specially challenging. Age-related issues
      do not allow for direct transposition of adult observations to this population.
      CXCR4 tropism has been associated with disease progression in adults. The
      geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3
      sequences, generating a false positive rate for a CXCR4 prediction. We evaluated
      the association of HIV-1 tropism prediction with clinical and laboratory outcome
      of 73 children with HIV/AIDS in Sao Paulo, Brazil. The CXCR4 tropism was strongly
      associated with a lower (nadir) CD4 documented during follow-up (p<0.0001) and
      with disease severity (clinical event and/or CD4 below 200cells/mm(3)) at the
      last observation, using commonly applied clinical cutoffs, such as (10%)FPRclonal
      (p=0.001). When variables obtained during follow-up are included, both treatment
      adherence and viral tropism show a significant association with disease severity.
      As for viremia suppression, 30% (22/73) were undetectable at the last
      observation, with only adherence strongly associated with suppression after
      adjustment. The study brings further support to the notion that antiretroviral
      treatment adherence is pivotal to management of HIV disease, but suggests that
      tropism prediction may provide an additional prognostic marker to monitor HIV
      disease in children. 

PMID- 24275367
TI  - Human herpesvirus-6 and cytomegalovirus DNA in liver donor biopsies and their
      correlation with HLA matches and acute cellular rejection.
AB  - Herpesvirus reactivation is common after liver transplantation. OBJECTIVE:
      Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6)
      DNA in liver donor biopsies, seeking to better understand issues involving human
      donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute
      cellular rejection. METHODS: Fifty-nine liver transplantation patients were
      investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies,
      using the Nested-PCR technique. The clinical donor information and HLA matches
      were obtained from the Sao Paulo State Transplant System. The recipients' records
      regarding acute cellular rejection were studied. RESULTS: Seven (11.8%) biopsies
      were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors
      with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for
      significant association (p=0.09), 22 recipients developed acute cellular
      rejection and 9/22 were positive for HLA-DR 15 (p=0.03; chi(2)=4.51), which was
      statistically significant in univariate analysis and showed a tendency after
      multivariate analysis (p=0.08). CONCLUSION: HHV-6 DNA was prevalent in liver
      donors studied as well as HLA-DR 15. These findings suggest that patients with
      HLA-DR 15 in liver donor biopsies develop more rejection after liver
      transplantation.

PMID- 24275368
TI  - Microbiology of the middle meatus compared to sputum in young patients with
      cystic fibrosis from Bahia - Brazil.
AB  - Lower airway infection is a major cause of morbidity and mortality in patients
      with cystic fibrosis. It is currently unknown if the infection of the upper
      airway can cause exacerbation of lower respiratory tract infection. This study
      aimed to determine the microbiological profile of the anterior paranasal sinuses
      outflow tract (middle meatus) of cystic fibrosis outpatients. The microbiological
      profile was defined using endoscopically directed middle meatal cultures. Paired
      middle meatal and sputum specimens were collected from 56 outpatients for aerobic
      cultures. A semi-quantitative leukocyte count of the middle meatal samples was
      performed. The median age of patients was nine years (3-20 years). Staphylococcus
      aureus (37%), Staphylococcus coagulase-negative (25%), Neisseriac (14%),
      Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (7%) were the most
      prevalent microorganisms in the middle meatal cultures. Using the middle meatal
      leukocyte count, 16 out of 54 patients (29.6%) presented sinus infection. The
      most frequently identified pathogens in patients with sinus infections were
      Staphylococcus aureus (10 patients), Pseudomonas aeruginosa (4 patients), and
      Streptococcus pneumoniae (3 patients). Agreement of paired middle meatal and
      sputum cultures was significantly higher among patients with infection in middle
      meatal (69%). The most common middle meatal pathogens were the typical cystic
      fibrosis spectrum. This suggests the potential for participating in post-nasal
      lower airway seeding. 

PMID- 24275369
TI  - Risk factors for mortality in burn children.
AB  - Studies about risk factors for mortality in burn children are scarce. We
      conducted this study to evaluate the risk factors for mortality in pediatric burn
      patients. We included 110 patients. Mean age was 31.5 months (range: 1 to 204).
      The burn surface was between 1% and 95%(median 27%) Type of burn was: A or
      superfitial in 39 patients (36%), AB or intermediate in 19 (17%), and B or full
      thickness in 52 (47%). Inhalatory injury was present in 52 patients (47%).
      Invasive procedures were: venous catheter, 90 patients (82%), arterial catheter,
      83 patients (75.5%), urinary catheter, 86 patients (78%), and mechanical
      ventilation, 75 patients (68%). In 84 patients, 128 infections were diagnosed. in
      53 cases (48%). Multiresistant Pseudomonas aeruginosa and Acynetobacter baumannii
      were the most common organisms isolated. The median length of hospital stay was
      33 days (r: 8-139 days). Seventeen patients (15%) died and 14 of them of
      infection-related causes. Age <= <4 years, Garces 4, full thickness burn, >= 40%
      burn surface, presence of inhalatory syndrome, use of venous catheter, arterial
      catheter, urinary catheter and mechanical ventilation, positive blood cultures,
      colistin use in documented multiresistant infections, antifungal use and graft
      requirement, were identified as risks factors for mortality in the univariate
      analysis. By multivariate analysis: age <= 4 years, Garces 4, colistin use in
      multiresistant infections, mechanical ventilation and graft requirement were
      independent variables related with mortality. CONCLUSIONS: In this series of burn
      children age <= 4 years, Garces index score 4, colistin use in documented
      multiresistant infections, mechanical ventilation and graft requirement were
      identified as independent variables related with mortality.

PMID- 24275370
TI  - Pertussis in the central-west region of Brazil: one decade study.
AB  - In many parts of the world, numerous outbreaks of pertussis have been described
      despite high vaccination coverage. In this article we report the epidemiological
      characteristics of pertussis in Brazil using a Surveillance Worksheet. Secondary
      data of pertussis case investigations reported from January 1999 to December 2008
      recorded in the Information System for Notifiable Diseases (SINAN) and the
      Central Laboratory for Public Health (LACEN-MS) were utilized. The total of 561
      suspected cases were reported and 238 (42.4%) of these were confirmed, mainly in
      children under six months (61.8%) and with incomplete immunization (56.3%). Two
      outbreaks were detected. Mortality rate ranged from 2.56% to 11.11%. The
      occurrence of outbreaks and the poor performance of cultures for confirming
      diagnosis are problems which need to be addressed. High vaccination coverage is
      certainly a good strategy to reduce the number of cases and to reduce the impact
      of the disease in children younger than six months. 

PMID- 24275371
TI  - Immune responses to Leptospira infection: roles as biomarkers for disease
      severity.
AB  - Various leptospiral components have been identified and shown to be involved in
      tissue destruction. In addition, immune responses to leptospires have been
      implicated in target organ damages in severe leptospirosis cases. Several
      inflammatory mediators were shown to be higher in susceptible animals than in
      resistant hosts. Moreover, cytokines/chemokines and serum proteins induced
      following Leptospira infection were suggested to be biomarkers for disease
      severity in human leptospirosis. This review focuses on the role of immune
      responses in the severity of leptospirosis. Studies in both animal models and
      humans are discussed. 

PMID- 24275372
TI  - Trends in overall opportunistic illnesses, Pneumocystis carinii pneumonia,
      cerebral toxoplasmosis and Mycobacterium avium complex incidence rates over the
      30 years of the HIV epidemic: a systematic review.
AB  - BACKGROUND: The natural history of HIV infection has changed dramatically after
      the introduction of highly active antiretroviral therapy. Currently,
      opportunistic illnesses still represent a major cause of death and
      hospitalization in this population. In this study, we review the trends in
      opportunistic illnesses incidence rates and compare the results observed in high
      income settings with that for low/middle-income settings, with special attention
      given to studies from Brazil. METHODS: We systematically searched Pubmed, Web of
      Science, Lilacs and Google scholar for publications on HIV associated
      opportunistic illness. Studies reporting rates based on person-time for all
      opportunistic illnesses and/or the three opportunistic infections of interest,
      namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium
      avium complex were included. RESULTS: Significant reductions in the incidence
      rates were demonstrated for opportunistic illnesses overall and also for the
      specific opportunistic infections included in the present study, both in high and
      low/middle-income settings. Out of the 37 studies included in the present review,
      almost 70% were from high-income settings. All the studies conducted in
      low/middle-income settings were single center studies and four were from Brazil.
      We found no study from Brazil reporting annual incidence rates of opportunistic
      illnesses. CONCLUSIONS: Opportunistic illnesses remain an important public health
      problem. To better guide health policies in low/middle-income settings,
      multicenter cohort studies should be encouraged. Studies from Brazil are urgently
      needed to assess the current burden of opportunistic illnesses in our population
      and to support the planning of HIV/AIDS health care services organization.

PMID- 24275373
TI  - Rifampin induced angioedema: a rare but serious side effect.

PMID- 24275374
TI  - Microsporum spp. onychomycosis: disease presentation, risk factors and treatment
      responses in an urban population.
AB  - BACKGROUND: Dermatophytes are the main causative agent of all onychomycosis, but
      genus Microsporum is infrequent and the risk of acquiring the infection is often
      associated with exposure to risk factors. OBJECTIVES: To describe clinical
      characteristics of onychomycosis due to Microsporum onychomycosis in an urban
      population. METHODS: This was a retrospective analysis of the epidemiological and
      clinical features of 18 Microsporum onychomycosis cases of a total of 4220 of
      onychomycosis cases diagnosed between May 2008 and September 2011 at the tertiary
      referral center for mycology in Guatemala. RESULTS: Eighteen cases of Microsporum
      onychomycosis (M. canis, n=10; M. gypseum, n=7; M. nanum, n=1) were identified
      (prevalence=0.43%). Infection was limited to nails only and disease duration
      ranged from 1 month to 20 years (mean=6.55 years). The toenails were affected in
      all cases except for a single M. gypseum case of fingernail. The most common
      clinical presentation was distal lateral subungual onychomycosis (12/18) followed
      by total dystrophic onychomycosis (5/18), and superficial white onychomycosis
      (1/18). M. gypseum presented in 6 cases as distal lateral subungual onychomycosis
      and in 1 case like total dystrophic onychomycosis. Five cases (27.78%) were
      associated with hypertension, diabetes, and psoriasis. Treatment with terbinafine
      or itraconazole was effective. Two cases of M. canis distal lateral subungual
      onychomycosis responded to photodynamic therapy. CONCLUSION: This is the largest
      reported series of Microsporum onychomycosis and demonstrates such a disease in
      an urban population. In 27.78% of the cases risk factors for infection were
      associated to comorbid states. We also report the first 2 cases of successfully
      treated M. canis onychomycosis with photodynamic therapy and a rare case of M.
      canis associated dermatophytoma.

PMID- 24275375
TI  - Epidemiology of healthcare-associated infections among patients from a
      hemodialysis unit in southeastern Brazil.
AB  - Patients submitted to hemodialysis are at a high risk for healthcare-associated
      infections (HAI). Presently there are scarce data to allow benchmarking of HAI
      rates in developing countries. Also, most studies focus only on bloodstream
      infections (BSI) or local access infections (LAI). Our study aimed to provide a
      wide overview of HAI epidemiology in a hemodialysis unit in southeastern Brazil.
      We present data from prospective surveillance carried out from March 2010 through
      May 2012. Rates were compared (mid-p exact test) and temporally analyzed in
      Shewhart control charts for Poisson distributions. The overall incidence of BSI
      was 1.12 per 1000 access-days. The rate was higher for patients performing
      dialysis through central venous catheters (CVC), either temporary (RR=13.35, 95%
      CI=6.68-26.95) or permanent (RR=2.10, 95% CI=1.09-4.13), as compared to those
      with arteriovenous fistula. Control charts identified a BSI outbreak caused by
      Pseudomonas aeruginosa in April 2010. LAI incidence was 3.80 per 1000 access
      days. Incidence rates for other HAI (per 1000 patients-day) were as follows:
      upper respiratory infections, 1.72; pneumonia, 1.35; urinary tract infections,
      1.25; skin/soft tissues infections, 0.93. The data point out to the usefulness of
      applying methods commonly used in hospital-based surveillance for hemodialysis
      units. 

PMID- 24275376
TI  - Carbapenemase KPC-2 in ESBL-producing Enterobacteriaceae from two clinics from
      Villavicencio, Colombia.

PMID- 24275377
TI  - Necrotizing fasciitis: eight-year experience and literature review.
AB  - OBJECTIVES: To describe clinical, laboratory, microbiological features, and
      outcomes of necrotizing fasciitis. METHODS: From January 1, 2004 to December 31,
      2011, 115 patients (79 males, 36 females) diagnosed with necrotizing fasciitis
      were admitted to Mackay Memorial Hospital in Taitung. Demographic data, clinical
      features, location of infection, type of comorbidities, microbiology and
      laboratory results, and outcomes of patients were retrospectively analyzed.
      RESULTS: Among 115 cases, 91 survived (79.1%) and 24 died (20.9%). There were 67
      males (73.6%) and 24 females (26.4%) with a median age of 54 years (inter
      quartile ranges, 44.0-68.0 years) in the survival group; and 12 males (50%) and
      12 females (50%) with a median age of 61 years (inter-quartile ranges, 55.5-71.5
      years) in the non-surviving group. The most common symptoms were local
      swelling/erythema, fever, pain/tenderness in 92 (80%), 87 (76%) and 84 (73%)
      patients, respectively. The most common comorbidies were liver cirrhosis in 54
      patients (47%) and diabetes mellitus in 45 patients (39%). A single organism was
      identified in 70 patients (61%), multiple pathogens were isolated in 20 patients
      (17%), and no microorganism was identified in 30 patients (26%). The significant
      risk factors were gender, hospital length of stay, and albumin level. DISCUSSION:
      Necrotizing fasciitis, although not common, can cause notable rates of morbidity
      and mortality. It is important to have a high index of suspicion and increase
      awareness in view of the paucity of specific cutaneous findings early in the
      course of the disease. Prompt diagnosis and early operative debridement with
      adequate antibiotics are vital.

PMID- 24275378
TI  - Coffee has hepatoprotective benefits in Brazilian patients with chronic hepatitis
      C even in lower daily consumption than in American and European populations.
AB  - The potential role of coffee as a hepatoprotective substance for chronic liver
      diseases has been widely discussed. Our main aim was to evaluate the effect of
      coffee intake regarding clinical, biochemical tests and liver biopsy data in
      treatment naive patients with chronic hepatitis C. One hundred and thirty-six
      patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of
      clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by
      determination of biochemical tests, metabolic and morphological alterations. Food
      frequency was scrutinized by using a structured questionnaire. Coffee intake
      represented more than 90% of the total daily caffeine, and the 75th percentile
      was 4-Brazilian coffee-cup/day (>= 255 mL/day or >= 123 mg caffeine/day).
      According to caffeine intake, patients were divided into two groups (< or >= 123
      mg caffeine/day). Patients with higher ingestion of caffeine had lower serum
      levels of aspartate aminotransferase (* upper limit of normal) (1.8 +/- 1.5 vs
      2.3 +/- 1.5, p=0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs
      54.5%, p<0.001) and of histological activity grade (A3, A4) observed in liver
      biopsies (13.8% vs 36.9%, p<0.001). By multivariate logistic regression, fibrosis
      was independently associated with caffeine intake (OR- 0.16; 95%CI - 0.03-0.80;
      p=0.026), gamma-glutamil transferase serum levels and morphological activity. But
      only fibrosis was associated with histological activity. In conclusion caffeine
      consumption greater than 123 mg/day was associated with reduced hepatic fibrosis.
      In addition, this study supports the assumption that coffee intake has
      hepatoprotective benefits for Brazilian patients with chronic hepatitis C, even
      in lower doses than that of American and European population intake.

PMID- 24275379
TI  - Correlated cryo-fluorescence and cryo-electron microscopy with high spatial
      precision and improved sensitivity.
AB  - Performing fluorescence microscopy and electron microscopy on the same sample
      allows fluorescent signals to be used to identify and locate features of interest
      for subsequent imaging by electron microscopy. To carry out such correlative
      microscopy on vitrified samples appropriate for structural cryo-electron
      microscopy it is necessary to perform fluorescence microscopy at liquid-nitrogen
      temperatures. Here we describe an adaptation of a cryo-light microscopy stage to
      permit use of high-numerical aperture objectives. This allows high-sensitivity
      and high-resolution fluorescence microscopy of vitrified samples. We describe and
      apply a correlative cryo-fluorescence and cryo-electron microscopy workflow
      together with a fiducial bead-based image correlation procedure. This procedure
      allows us to locate fluorescent bacteriophages in cryo-electron microscopy images
      with an accuracy on the order of 50 nm, based on their fluorescent signal. It
      will allow the user to precisely and unambiguously identify and locate objects
      and events for subsequent high-resolution structural study, based on fluorescent
      signals.

PMID- 24275380
TI  - Does comprehension of symbolic gestures and corresponding-in-meaning words make
      use of motor simulation?
AB  - The present study aimed at determining whether or not the comprehension of
      symbolic gestures, and corresponding-in-meaning words, makes use of cortical
      circuits involved in movement execution control. Participants were presented with
      videos of an actress producing meaningful or meaningless gestures, pronouncing
      corresponding-in-meaning words or pseudo-words; they were required to judge
      whether the signal was meaningful or meaningless. Single pulse TMS was applied to
      forearm primary motor cortex area 150-200 ms after the point when the stimulus
      meaning could be understood. MEPs were significantly greater when processing
      meaningless signals as compared to a baseline condition presenting a still-and
      silent actress. In contrast, this was not the case for meaningful signals whose
      motor activation did not differ from that for the baseline stimulus. MEPs were
      significantly greater for meaningless than meaningful signals and no significant
      difference was found between gesture and speech. On the basis of these results,
      we hypothesized that the observation-of/listening-to meaningless signals recruits
      motor areas. In contrast, this did not occur when the signals were meaningful.
      Overall, the data suggest that the processes related to comprehension of symbolic
      gestures and communicative words do not involve primary motor area and probably
      use brain areas involved in semantics.

PMID- 24275381
TI  - Behaviorally inhibited individuals demonstrate significantly enhanced conditioned
      response acquisition under non-optimal learning conditions.
AB  - Behavioral inhibition (BI) is an anxiety vulnerability factor associated with
      hypervigilance to novel stimuli, threat, and ambiguous cues. The progression from
      anxiety risk to a clinical disorder is unknown, although the acquisition of
      defensive learning and avoidance may be a critical feature. As the expression of
      avoidance is also central to anxiety development, the present study examined
      avoidance acquisition as a function of inhibited temperament using classical
      eyeblink conditioning. Individuals were classified as behaviorally inhibited (BI)
      or non-inhibited (NI) based on combined scores from the Adult and Retrospective
      Measures of Behavioural Inhibition (AMBI and RMBI, respectively). Acquisition was
      assessed using delay, omission, or yoked conditioning schedules of reinforcement.
      Omission training was identical to delay, except that the emission of an eyeblink
      conditioned response (CR) resulted in omission of the unconditioned airpuff
      stimulus (US) on that trial. Each subject in the yoked group was matched on total
      BI score to a subject in the omission group, and received the same schedule of CS
      and US delivery, resulting in a partial reinforcement training schedule. Delay
      conditioning elicited significantly more CRs compared to the omission and yoked
      contingencies, the latter two of which did not differ from each other. Thus,
      acquisition of an avoidance response was not apparent. BI individuals
      demonstrated enhanced acquisition overall, while partial reinforcement training
      significantly distinguished between BI and NI groups. Enhanced learning in BI may
      be a function of an increased defensive learning capacity, or sensitivity to
      uncertainty. Further work examining the influence of BI on learning acquisition
      is important for understanding individual differences in disorder etiology in
      anxiety vulnerable cohorts. 

PMID- 24275382
TI  - Cell biology - consultant for the clinic.

PMID- 24275383
TI  - Of fish and men: using zebrafish to fight human diseases.
AB  - Long restricted to the field of developmental biology, the use of the zebrafish
      (Danio rerio) has extended to the study of human pathogenesis. Fostered by the
      rapid adaptation of new technologies, the design and analysis of fish models of
      human diseases have contributed important findings that are now making their way
      from aquariums to clinics. Here we outline the clinical relevance of the
      zebrafish as a model organism. 

PMID- 24275384
TI  - Cisplatin, oxaliplatin, and carboplatin unequally inhibit in vitro mRNA
      translation.
AB  - DNA is considered the preferential target of platinum containing cytostatics such
      as cisplatin, oxaliplatin, and carboplatin. Despite profound knowledge on the
      interaction between platinum drugs and DNA, there is little data on the
      interaction with mRNA and even less on the potential differences among these
      antineoplastic agents to inhibit protein synthesis. We therefore established an
      in vitro translation system using in vitro transcribed mRNA encoding green
      fluorescent protein (GFP) to evaluate the effects of exposure of GFP mRNA to 0
      100 MUM of cisplatin, oxaliplatin, or carboplatin. We additionally investigated
      the interaction between these drugs and mRNA through evaluation of crossing
      points during quantitative real-time polymerase chain reactions. In contrast to
      oxaliplatin or carboplatin, 100 MUM cisplatin significantly increased crossing
      points by about 3 cycles (P<0.01) and profoundly attenuated translation of GFP
      mRNA (P<0.05). Oxaliplatin showed a trend to reduce GFP mRNA translation, whereas
      carboplatin entirely failed to influence it. In conclusion, this study for the
      very first time documents different effects of platinum cytostatics on mRNA
      translation and demonstrates mRNA to be a functionally relevant target of at
      least cisplatin.

PMID- 24275385
TI  - Genotoxic risk in rubber manufacturing industry: a systematic review.
AB  - A large body of evidence from epidemiological studies among workers employed in
      the rubber manufacturing industry has indicated a significant excess cancer risk
      in a variety of sites. The International Agency for Research on Cancer has
      recently classified the "Occupational exposures in the rubber-manufacturing
      industry" as carcinogenic to humans (Group 1). A genotoxic mechanism for the
      increased cancer risk was suggested on the basis of the evidence from the
      scientific literature. Exposure assessment studies have shown that workers in the
      rubber manufacturing industry may be exposed to different airborne carcinogenic
      and/or genotoxic chemicals, such as certain aromatic amines, polycyclic aromatic
      hydrocarbons, N-nitrosamines, although the available information does not allow
      to establish a causal association of cancer or genotoxic risk with particular
      substances/classes of chemicals or specific jobs. The aim of this paper is to
      critically evaluate, by conducting a systematic review, the available
      biomonitoring studies using genotoxicity biomarkers in rubber manufacturing
      industry. This systematic review suggests that a genotoxic hazard may still be
      present in certain rubber manufacturing industries. A quantitative risk
      assessment needs further studies addressing the different, processes and
      chemicals in the rubber manufacturing industries. 

PMID- 24275387
TI  - Spin-dependent thermoelectric properties of a Kondo-correlated quantum dot with
      Rashba spin-orbit coupling.
AB  - Thermoelectric transport phenomena in a single-level quantum dot coupled to
      ferromagnetic leads are considered theoretically in the Kondo regime. The dot is
      described by the Anderson model with Rashba type spin-orbit interactions. The
      finite-U mean field slave boson technique is used to describe transport
      characteristics, such as the heat conductance, thermopower and thermoelectric
      efficiency (figure of merit). The role of quantum interference effects in the
      thermoelectric parameters is also analyzed. 

PMID- 24275386
TI  - Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and
      early fibrosis.
AB  - Acute kidney injury (AKI) is a disease with mitochondrial dysfunction and a newly
      established risk factor for the development of chronic kidney disease (CKD) and
      fibrosis. We examined mitochondrial homeostasis in the folic acid (FA)-induced
      AKI model that develops early fibrosis over a rapid time course. Mice given a
      single dose of FA had elevated serum creatinine (3-fold) and urine glucose (2.2
      fold) 1 and 2 d after injection that resolved by 4d. In contrast, peroxisome
      proliferator gamma coactivator 1alpha (PGC-1alpha) and mitochondrial
      transcription factor A (TFAM), critical transcriptional regulators of
      mitochondrial biogenesis (MB), were down-regulated ~80% 1d after FA injection and
      remained depressed through 14 d. Multiple electron transport chain and ATP
      synthesis genes were also down-regulated from 1 to 14 d after FA, including NADH
      dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUFbeta8), ATP synthase subunit
      beta (ATPS-beta), and cytochrome C oxidase subunit I (COXI). Mitochondrial DNA
      copy number was reduced ~50% from 2 to 14 d after FA injection. Protein levels of
      early fibrosis markers alpha-smooth muscle actin and transforming growth factor
      beta1 were elevated at 6 and 14 d after FA. Picrosirius red staining and collagen
      1A2 (COL1A2) IHC revealed staining for mature collagen deposition at 14 d. We
      propose that mitochondrial dysfunction induced by AKI is a persistent cellular
      injury that promotes progression to fibrosis and CKD, and that this model can be
      used to test mitochondrial therapeutics that limit progression to fibrosis and
      CKD.

PMID- 24275388
TI  - The swan song of the pulmonary artery catheter.

PMID- 24275389
TI  - End-of-life care and the withdrawal of cardiorespiratory life support: are
      practice recommendations trustworthy?

PMID- 24275390
TI  - Everything should be made as simple as possible, but not simpler.

PMID- 24275391
TI  - Goal-directed advanced cardiac life support: coronary perfusion pressure as a
      target during resuscitation.

PMID- 24275392
TI  - Balancing the quality of care we provide our current versus future patients: are
      we doing the right thing?

PMID- 24275393
TI  - Goldilocks in the ICU: too few beds, too many, or just right?

PMID- 24275394
TI  - Diabetes and acute respiratory distress syndrome: can we finally believe the
      epidemiology?

PMID- 24275395
TI  - The guest who would not leave.

PMID- 24275396
TI  - Feeding ICU patients on invasive mechanical ventilation: designing the optimal
      protocol.

PMID- 24275397
TI  - Skipping along the yellow brick road: unifying critical care medicine and
      training.

PMID- 24275398
TI  - More, please.

PMID- 24275399
TI  - Readmission after intracerebral hemorrhage: can we really predict the future?

PMID- 24275400
TI  - Back to the PICU: who is at risk and outcome of unplanned readmissions.

PMID- 24275401
TI  - Cardiopulmonary resuscitation: saving life then saving organs?

PMID- 24275402
TI  - Platelet: RBC ratios: randomized controlled trials are needed for optimal
      resuscitation of injured patients.

PMID- 24275403
TI  - Is the time right to fight global warming in sepsis?

PMID- 24275404
TI  - Alveolar recruitment and lung injury: an issue of timing and location?

PMID- 24275405
TI  - alpha(2)-agonists to restore adrenergic vasoconstrictor responsiveness in septic
      shock: thinking outside of the box or fishing in the wrong pond?

PMID- 24275406
TI  - Environmental sources apart from air need to be investigated first.

PMID- 24275407
TI  - The authors reply.

PMID- 24275408
TI  - Noninvasive mechanical ventilation and sleep quality in ICU: intensivists are
      waking up!

PMID- 24275409
TI  - The authors reply.

PMID- 24275410
TI  - Vasopressin guidelines in surviving sepsis campaign: 2012.

PMID- 24275411
TI  - The authors reply.

PMID- 24275412
TI  - Vasopressor dosing in septic shock.

PMID- 24275413
TI  - The authors reply.

PMID- 24275414
TI  - Fluid therapy in severe sepsis and septic shock.

PMID- 24275415
TI  - The authors reply.

PMID- 24275416
TI  - Surviving sepsis guidelines 2012.

PMID- 24275417
TI  - The author replies.

PMID- 24275418
TI  - Comments on surviving sepsis guideline 2012.

PMID- 24275419
TI  - The authors reply.

PMID- 24275420
TI  - Inclusion and recommendation of (1->3)-beta-D-glucan testing in the international
      guidelines for management of severe sepsis and septic shock.

PMID- 24275421
TI  - The authors reply.

PMID- 24275422
TI  - The worth of the guidelines: pediatric considerations in severe sepsis and septic
      shock.

PMID- 24275423
TI  - The author replies.

PMID- 24275424
TI  - Meaning of the venoarterial carbon dioxide difference/arterial-venous oxygen
      difference ratio.

PMID- 24275425
TI  - The authors reply.

PMID- 24275426
TI  - A ruptured omental aneurysm, a rare cause of intraabdominal bleeding.
AB  - Of all splanchnic artery aneurysms, the omental artery aneurysm is the most
      uncommon. In the published literature, there is no report of an incidental
      diagnosis, and all were discovered only after rupture. Until now, this is only
      the sixth case of a ruptured omental aneurysm published, and the first case with
      a concomitant nonruptured omental aneurysm. 

PMID- 24275427
TI  - What is the true incidence of anomalous bovine left common carotid artery
      configuration?
AB  - BACKGROUND: Earlier studies have indicated that bovine left common carotid artery
      configuration occurs in 10.2-22% of patients and increases the complexity of
      navigating endovascular devices in the aortic arch. However, we anecdotally noted
      a higher incidence of bovine arch among angiosuite outpatients in Los Angeles,
      California. Thus, we retrospectively reviewed aortic arch angiograms performed in
      93 unique outpatients to determine the true incidence of this anomalous
      configuration. METHODS: We were able to obtain complete angiographies from
      clinical data on 90 patients (mean age 50 years, SD 15.23 years, range 17-88
      years) from May 2006 to January 2012. Angiograms were categorized as: normal
      arch; bovine arch with brachiocephalic trunk; bovine arch with common trunk; or
      indeterminate. RESULTS: The findings indicated an overall 35.16% bovine arch
      incidence, of which 78.13% is bovine arch with common trunk and 21.88% is bovine
      arch with brachiocephalic trunk. There was a higher prevalence in the women (40%,
      n = 60) than men (26.67%, n = 30). Caucasians had a lower incidence of bovine
      arch (27.78%, n = 47) compared with other ethnicities. The prevalence of bovine
      arch in different ethnicity and gender groups was assessed and the differences
      were not statistically significant. CONCLUSIONS: The incidence of bovine left
      common carotid artery is higher than previously reported and varies by gender and
      race. Advanced knowledge of the high prevalence of this anomaly could reduce the
      risks and increase the efficiency of navigating catheters through the tortuous
      vessels during endovascular procedures. The clinical implications of this report
      warrant further investigation.

PMID- 24275428
TI  - De novo periaortic fibrosis after endovascular aortic repair.
AB  - We report a case of a 63-year-old man presenting with abdominal pain and
      hydronephrosis secondary to periaortic fibrosis (PAF) 8 months after an
      endovascular aortic repair (EVAR) using a woven polyester bifurcated graft. De
      novo delayed PAF after open repair is rare and even more infrequent after EVAR.
      All 3 previously reported cases occurred after woven polyester grafts and no
      reported cases after polytetrafluorethylene grafts. Management included steroidal
      anti-inflammatory treatment and bilateral double J tube placement. Satisfactory
      results were obtained.

PMID- 24275429
TI  - Do health provider-patient relationships matter? Exploring dentist-patient
      relationships and oral health-related quality of life in older people.
AB  - BACKGROUND: patient experience is now a key parameter in health care. Yet, very
      little is known about the possible impact of dentist-patient relationships on
      patient-centred outcomes including older peoples' oral health-related quality of
      life (OHRQoL). OBJECTIVE: this study assessed the relationship between OHRQoL and
      dentist-patient relationships related to perceived unmet dental needs; shared
      decision-making; time spent discussing oral health problems; respect and
      confidence and trust. PARTICIPANTS: older people aged 65 years and over living in
      East London, U.K. in 2011. METHODS: a cross-sectional study using stratified
      random sampling recruited a representative sample of older people (n = 772).
      PARTICIPANTS completed an oral examination and a structured questionnaire
      including the Oral Health Impact Profile-14 (OHIP-14) measuring OHRQoL and five
      dentist-patient relationship questions taken from the U.K. 2009 Adult Dental
      Health Survey. Multivariate Poisson regressions modelled the association between
      OHRQoL and dentist-patient factors adjusting for socio-demographic factors,
      clinical oral indicators, and dental attendance. RESULTS: having a perceived
      unmet need for dental treatment (PRR = 1.84; 95% CI: 1.32, 2.56) and expressing a
      lack of trust and confidence in one's dentist (PRR = 1.74; 95% CI: 1.01, 2.98)
      were significant predictors of poor OHRQoL among older people. CONCLUSIONS: these
      findings suggest that older people with unmet dental needs and those who
      expressed a lack of trust and confidence in their dentist were more likely to
      experience poor OHRQoL reinforcing the importance of the dental patient
      experience in healthy ageing and well-being.

PMID- 24275430
TI  - Molecular forms of the insulin-like growth factor-binding protein-2 in patients
      with colorectal cancer.
AB  - The components of the insulin-like growth factor (IGF) system and molecules with
      which they interact are associated with the neoplastic transformation of cells in
      colorectal cancer. The IGF-binding protein-2 (IGFBP-2) plays a significant role
      in mitotic stimulation of the cancer cells and its concentration is significantly
      elevated in tumor states. Little is known about IGFBP-2 at the molecular level
      and the purpose of this study was to examine the interactions between IGFBP-2 and
      some other proteins, the fragmentation pattern and posttranslational
      modifications that might have occurred due to a disease. Results have shown that
      the amount of monomer IGFBP-2 was 20-30% greater in patients with cancer and the
      amount of fragmented IGFBP-2 was doubled compared to healthy people, whereas the
      portion of IGFBP-2 in complex with alpha2 macroglobulin (alpha2M) was 2.5 times
      lower in cancer patients. According to this distribution, IGFBP-2 was not only
      increasingly synthetized in patients with cancer, but also the amount involved in
      complexes with alpha2M was reduced favoring the existence of binary IGFBP-2/IGF
      complexes, free to leave the circulation. Both IGFBP-2 and alpha2M were
      significantly more oxidized in patients with colon cancer than in healthy
      individuals and alpha2M was additionally sialylated. It can be speculated that
      the formation of IGFBP-2/alpha2M complexes is part of the control mechanism
      involved in the regulation of IGFBP-2 and, consequently, IGF availability. It
      also seems that posttranslational modifications are more important factors in
      determining the amount of IGFBP-2/alpha2M complexes than the actual quantity of
      these two proteins. 

PMID- 24275431
TI  - Re: Factors predictive of macrosomia in pregnancies with a positive oral glucose
      challenge test: importance of fasting plasma glucose.

PMID- 24275432
TI  - Insights into mRNA export-linked molecular mechanisms of human disease through a
      Gle1 structure-function analysis.
AB  - A critical step during gene expression is the directional export of nuclear
      messenger (m)RNA through nuclear pore complexes (NPCs) to the cytoplasm. During
      export, Gle1 in conjunction with inositol hexakisphosphate (IP6) spatially
      regulates the activity of the DEAD-box protein Dbp5 at the NPC cytoplasmic face.
      GLE1 mutations are causally linked to the human diseases lethal congenital
      contracture syndrome 1 (LCCS-1) and lethal arthrogryposis with anterior horn cell
      disease (LAAHD). Here, structure prediction and functional analysis provide
      strong evidence to suggest that the LCCS-1 and LAAHD disease mutations disrupt
      the function of Gle1 in mRNA export. Strikingly, direct fluorescence microscopy
      in living cells reveals a dramatic loss of steady-state NPC localization for GFP
      gle1 proteins expressed from human gle1 genes harboring LAAHD and LCCS-1
      mutations. The potential significance of these residues is further clarified by
      analyses of sequence and predicted structural conservation. This work offers
      insights into the perturbed mechanisms underlying human LCCS-1 and LAAHD disease
      states and emphasizes the potential impact of altered mRNA transport and gene
      expression in human disease. 

PMID- 24275433
TI  - Autonomic nerve activity and blood pressure in ambulatory dogs.
AB  - BACKGROUND: The relationship between cardiac autonomic nerve activity and blood
      pressure (BP) changes in ambulatory dogs is unclear. OBJECTIVE: The purpose of
      this study was to test the hypotheses that simultaneous termination of stellate
      ganglion nerve activity (SGNA) and vagal nerve activity (VNA) predisposes to
      spontaneous orthostatic hypotension and that specific beta2-adrenoceptor blockade
      prevents the hypotensive episodes. METHODS: We used a radiotransmitter to record
      SGNA, VNA, and BP in eight ambulatory dogs. Video imaging was used to document
      postural changes. RESULTS: Of these eight dogs, five showed simultaneous
      sympathovagal discharges in which the minute-by-minute integrated SGNA correlated
      with integrated VNA in a linear pattern (group 1). In these dogs, abrupt
      termination of simultaneous SGNA-VNA at the time of postural changes (as
      documented by video imaging) was followed by abrupt (>20 mm Hg over four beats)
      drops in BP. Dogs without simultaneous on/off firing (group 2) did not have
      drastic drops in pressure. ICI-118,551 (ICI, a specific beta2-blocker) infused at
      3 ug/kg/h for 7 days significantly increased BP from 126 mm Hg (95% confidence
      interval 118-133) to 133 mm Hg (95% confidence interval 125-141; P = .0001). The
      duration of hypotension (mean systolic BP <100 mm Hg) during baseline accounted
      for 7.1% of the recording. The percentage was reduced by ICI to 1.3% (P = .01).
      CONCLUSION: Abrupt simultaneous termination of SGNA-VNA was observed at the time
      of orthostatic hypotension in ambulatory dogs. Selective beta2-adrenoceptor
      blockade increased BP and reduced the duration of hypotension in this model.

PMID- 24275434
TI  - An inverse modeling approach for stress estimation in mitral valve anterior
      leaflet valvuloplasty for in-vivo valvular biomaterial assessment.
AB  - Estimation of regional tissue stresses in the functioning heart valve remains an
      important goal in our understanding of normal valve function and in developing
      novel engineered tissue strategies for valvular repair and replacement. Methods
      to accurately estimate regional tissue stresses are thus needed for this purpose,
      and in particular to develop accurate, statistically informed means to validate
      computational models of valve function. Moreover, there exists no currently
      accepted method to evaluate engineered heart valve tissues and replacement heart
      valve biomaterials undergoing valvular stresses in blood contact. While we have
      utilized mitral valve anterior leaflet valvuloplasty as an experimental approach
      to address this limitation, robust computational techniques to estimate implant
      stresses are required. In the present study, we developed a novel numerical
      analysis approach for estimation of the in-vivo stresses of the central region of
      the mitral valve anterior leaflet (MVAL) delimited by a sonocrystal transducer
      array. The in-vivo material properties of the MVAL were simulated using an
      inverse FE modeling approach based on three pseudo-hyperelastic constitutive
      models: the neo-Hookean, exponential-type isotropic, and full collagen-fiber
      mapped transversely isotropic models. A series of numerical replications with
      varying structural configurations were developed by incorporating measured
      statistical variations in MVAL local preferred fiber directions and fiber splay.
      These model replications were then used to investigate how known variations in
      the valve tissue microstructure influence the estimated ROI stresses and its
      variation at each time point during a cardiac cycle. Simulations were also able
      to include estimates of the variation in tissue stresses for an individual
      specimen dataset over the cardiac cycle. Of the three material models, the
      transversely anisotropic model produced the most accurate results, with ROI
      averaged stresses at the fully-loaded state of 432.6+/-46.5 kPa and 241.4+/-40.5
      kPa in the radial and circumferential directions, respectively. We conclude that
      the present approach can provide robust instantaneous mean and variation
      estimates of tissue stresses of the central regions of the MVAL. 

PMID- 24275435
TI  - Specimen-specific modeling of hip fracture pattern and repair.
AB  - Hip fracture remains a major health problem for the elderly. Clinical studies
      have assessed fracture risk based on bone quality in the aging population and
      cadaveric testing has quantified bone strength and fracture loads. Prior modeling
      has primarily focused on quantifying the strain distribution in bone as an
      indicator of fracture risk. Recent advances in the extended finite element method
      (XFEM) enable prediction of the initiation and propagation of cracks without
      requiring a priori knowledge of the crack path. Accordingly, the objectives of
      this study were to predict femoral fracture in specimen-specific models using the
      XFEM approach, to perform one-to-one comparisons of predicted and in vitro
      fracture patterns, and to develop a framework to assess the mechanics and load
      transfer in the fractured femur when it is repaired with an osteosynthesis
      implant. Five specimen-specific femur models were developed from in vitro
      experiments under a simulated stance loading condition. Predicted fracture
      patterns closely matched the in vitro patterns; however, predictions of fracture
      load differed by approximately 50% due to sensitivity to local material
      properties. Specimen-specific intertrochanteric fractures were induced by
      subjecting the femur models to a sideways fall and repaired with a contemporary
      implant. Under a post-surgical stance loading, model-predicted load sharing
      between the implant and bone across the fracture surface varied from 59%:41% to
      89%:11%, underscoring the importance of considering anatomic and fracture
      variability in the evaluation of implants. XFEM modeling shows potential as a
      macro-level analysis enabling fracture investigations of clinical cohorts,
      including at-risk groups, and the design of robust implants. 

PMID- 24275436
TI  - An analytical model to predict interstitial lubrication of cartilage in migrating
      contact areas.
AB  - For nearly a century, articular cartilage has been known for its exceptional
      tribological properties. For nearly as long, there have been research efforts to
      elucidate the responsible mechanisms for application toward biomimetic bearing
      applications. It is now widely accepted that interstitial fluid pressurization is
      the primary mechanism responsible for the unusual lubrication and load bearing
      properties of cartilage. Although the biomechanics community has developed
      elegant mathematical theories describing the coupling of solid and fluid
      (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps
      in our understanding of cartilage tribology have inhibited our ability to predict
      how tribological conditions and material properties impact tissue function. This
      paper presents an analytical model of the interstitial lubrication of biphasic
      materials under migrating contact conditions. Although finite element and other
      numerical models of cartilage mechanics exist, they typically neglect the
      important role of the collagen network and are limited to a specific set of input
      conditions, which limits general applicability. The simplified approach taken in
      this work aims to capture the broader underlying physics as a starting point for
      further model development. In agreement with existing literature, the model
      indicates that a large Peclet number, Pe, is necessary for effective interstitial
      lubrication. It also predicts that the tensile modulus must be large relative to
      the compressive modulus. This explains why hydrogels and other biphasic materials
      do not provide significant interstitial pressure under high Pe conditions. The
      model quantitatively agrees with in-situ measurements of interstitial load
      support and the results have interesting implications for tissue engineering and
      osteoarthritis problems. This paper suggests that a low tensile modulus (from
      chondromalacia or local collagen rupture after impact, for example) may disrupt
      interstitial pressurization, increase shear stresses, and activate a condition of
      progressive surface damage as a potential precursor of osteoarthritis. 

PMID- 24275438
TI  - Hemodynamics in coronary arteries with overlapping stents.
AB  - Coronary artery stenosis is commonly treated by stent placement via percutaneous
      intervention, at times requiring multiple stents that may overlap. Stent overlap
      is associated with increased risk of adverse clinical outcome. While changes in
      local blood flow are suspected to play a role therein, hemodynamics in arteries
      with overlapping stents remain poorly understood. In this study we analyzed six
      cases of partially overlapping stents, placed ex vivo in porcine left coronary
      arteries and compared them to five cases with two non-overlapping stents. The
      stented vessel geometries were obtained by micro-computed tomography of corrosion
      casts. Flow and shear stress distribution were calculated using computational
      fluid dynamics. We observed a significant increase in the relative area exposed
      to low wall shear stress (WSS<0.5 Pa) in the overlapping stent segments compared
      both to areas without overlap in the same samples, as well as to non-overlapping
      stents. We further observed that the configuration of the overlapping stent
      struts relative to each other influenced the size of the low WSS area:
      positioning of the struts in the same axial location led to larger areas of low
      WSS compared to alternating struts. Our results indicate that the overlap
      geometry is by itself sufficient to cause unfavorable flow conditions that may
      worsen clinical outcome. While stent overlap cannot always be avoided, improved
      deployment strategies or stent designs could reduce the low WSS burden.

PMID- 24275437
TI  - The mechanical microenvironment of high concentration agarose for applying
      deformation to primary chondrocytes.
AB  - Cartilage and chondrocytes experience loading that causes alterations in
      chondrocyte biological activity. In vivo chondrocytes are surrounded by a
      pericellular matrix with a stiffness of ~25-200kPa. Understanding the mechanical
      loading environment of the chondrocyte is of substantial interest for
      understanding chondrocyte mechanotransduction. The first objective of this study
      was to analyze the spatial variability of applied mechanical deformations in
      physiologically stiff agarose on cellular and sub-cellular length scales.
      Fluorescent microspheres were embedded in physiologically stiff agarose
      hydrogels. Microsphere positions were measured via confocal microscopy and used
      to calculate displacement and strain fields as a function of spatial position.
      The second objective was to assess the feasibility of encapsulating primary human
      chondrocytes in physiologically stiff agarose. The third objective was to
      determine if primary human chondrocytes could deform in high-stiffness agarose
      gels. Primary human chondrocyte viability was assessed using live-dead imaging
      following 24 and 72h in tissue culture. Chondrocyte shape was measured before and
      after application of 10% compression. These data indicate that (1) displacement
      and strain precision are ~1% and 6.5% respectively, (2) high-stiffness agarose
      gels can maintain primary human chondrocyte viability of >95%, and (3)
      compression of chondrocytes in 4.5% agarose can induce shape changes indicative
      of cellular compression. Overall, these results demonstrate the feasibility of
      using high-concentration agarose for applying in vitro compression to
      chondrocytes as a model for understanding how chondrocytes respond to in vivo
      loading. 

PMID- 24275439
TI  - A novel in vitro loading system to produce supraphysiologic oscillatory fluid
      shear stress.
AB  - A multi-well fluid loading (MFL) system was developed to deliver oscillatory
      subphysiologic to supraphysiologic fluid shear stresses to cell monolayers in
      vitro using standard multi-well culture plates. Computational fluid dynamics
      modeling with fluid-structure interactions was used to quantify the squeeze film
      fluid flow between an axially displaced piston and the well plate surface.
      Adjusting the cone angle of the piston base modulated the fluid pressure,
      velocity, and shear stress magnitudes. Modeling results showed that there was
      near uniform fluid shear stress across the well with a linear drop in pressure
      across the radius of the well. Using the MFL system, RAW 264.7 osteoclastic cells
      were exposed to oscillatory fluid shear stresses of 0, 0.5, 1.5, 4, 6, and 17 Pa.
      Cells were loaded 1 h per day at 1 Hz for two days. Compared to sub-physiologic
      and physiologic levels, supraphysiologic oscillatory fluid shear induced
      upregulation of osteoclastic activity as measured by tartrate-resistant acid
      phosphatase activity and formation of mineral resorption pits. Cell number
      remained constant across all treatment groups.

PMID- 24275441
TI  - Leg stiffness and joint stiffness while running to and jumping over an obstacle.
AB  - During running, muscles of the lower limb act like a linear spring bouncing on
      the ground. When approaching an obstacle, the overall stiffness of this leg
      spring system (k(leg)) is modified during the two steps preceding the jump to
      enhance the movement of the center of mass of the body while leaping the
      obstacle. The aim of the present study is to understand how k(leg) is modified
      during the running steps preceding the jump. Since k(leg) depends on the joint
      torsional stiffness and on the leg geometry, we analyzed the changes in these two
      parameters in eight subjects approaching and leaping a 0.65 m-high barrier at 15
      km h(-1). Ground reaction force (F) was measured during 5-6 steps preceding the
      obstacle using force platform and the lower limb movements were recorded by
      camera. From these data, the net muscular moment (M(j)), the angular displacement
      (theta(j)) and the lever arm of F were evaluated at the hip, knee and ankle. At
      the level of the hip, the M(j)-theta(j) relation shows that muscles are not
      acting like torsional springs. At the level of the knee and ankle, the M(j)
      theta(j) relation shows that muscles are acting like torsional springs: as
      compared to steady-state running, the torsional stiffness k(j) decreases from
      ~1/3 two contacts before the obstacle, and increases from ~2/3 during the last
      contact. These modifications in k(j) reflect in changes in the magnitude of F but
      also to changes in the leg geometry, i.e. in the lever arms of F.

PMID- 24275440
TI  - Control of dynamic foot-ground interactions in male and female soccer athletes:
      females exhibit reduced dexterity and higher limb stiffness during landing.
AB  - Controlling dynamic interactions between the lower limb and ground is important
      for skilled locomotion and may influence injury risk in athletes. It is well
      known that female athletes sustain anterior cruciate ligament (ACL) tears at
      higher rates than male athletes, and exhibit lower extremity biomechanics thought
      to increase injury risk during sport maneuvers. The purpose of this study was to
      examine whether lower extremity dexterity (LED)--the ability to dynamically
      control endpoint force magnitude and direction as quantified by compressing an
      unstable spring with the lower limb at submaximal forces--is a potential
      contributing factor to the "at-risk" movement behavior exhibited by female
      athletes. We tested this hypothesis by comparing LED-test performance and single
      limb drop jump biomechanics between 14 female and 14 male high school soccer
      players. We found that female athletes exhibited reduced LED-test performance
      (p=0.001) and higher limb stiffness during landing (p=0.008) calculated on
      average within 51 ms of foot contact. Females also exhibited higher coactivation
      at the ankle (p=0.001) and knee (p=0.02) before landing. No sex differences in
      sagittal plane joint angles and center of mass velocity at foot contact were
      observed. Collectively, our results raise the possibility that the higher leg
      stiffness observed in females during landing is an anticipatory behavior due in
      part to reduced lower extremity dexterity. The reduced lower extremity dexterity
      and compensatory stiffening strategy may contribute to the heightened risk of ACL
      injury in this population.

PMID- 24275443
TI  - Nonadiabatic time-dependent spin-density functional theory for strongly
      correlated systems.
AB  - We propose a nonadiabatic time-dependent spin-density functional theory (TDSDFT)
      approach for studying single-electron excited states and the ultrafast response
      of systems with strong electron correlations. The correlation part of the
      nonadiabatic exchange-correlation (XC) kernel is constructed by using exact
      results for the Hubbard model of strongly correlated electrons. We demonstrate
      that the corresponding nonadiabatic XC kernel reproduces the main features of the
      spectrum of the Hubbard dimer and the 2D, 3D and infinite-dimensional Hubbard
      models, some of which are impossible to obtain within the adiabatic approach. The
      formalism may be applied for ab initio examination of strongly correlated
      electron systems in- and out-of-equilibrium within the TDSDFT, extending it
      beyond the metallic and semiconductor structures with plasmons, excitons and
      other excitations. 

PMID- 24275442
TI  - A high throughput mechanical screening device for cartilage tissue engineering.
AB  - Articular cartilage enables efficient and near-frictionless load transmission,
      but suffers from poor inherent healing capacity. As such, cartilage tissue
      engineering strategies have focused on mimicking both compositional and
      mechanical properties of native tissue in order to provide effective repair
      materials for the treatment of damaged or degenerated joint surfaces. However,
      given the large number design parameters available (e.g. cell sources, scaffold
      designs, and growth factors), it is difficult to conduct combinatorial
      experiments of engineered cartilage. This is particularly exacerbated when
      mechanical properties are a primary outcome, given the long time required for
      testing of individual samples. High throughput screening is utilized widely in
      the pharmaceutical industry to rapidly and cost-effectively assess the effects of
      thousands of compounds for therapeutic discovery. Here we adapted this approach
      to develop a high throughput mechanical screening (HTMS) system capable of
      measuring the mechanical properties of up to 48 materials simultaneously. The
      HTMS device was validated by testing various biomaterials and engineered
      cartilage constructs and by comparing the HTMS results to those derived from
      conventional single sample compression tests. Further evaluation showed that the
      HTMS system was capable of distinguishing and identifying 'hits', or factors that
      influence the degree of tissue maturation. Future iterations of this device will
      focus on reducing data variability, increasing force sensitivity and range, as
      well as scaling-up to even larger (96-well) formats. This HTMS device provides a
      novel tool for cartilage tissue engineering, freeing experimental design from the
      limitations of mechanical testing throughput. 

PMID- 24275444
TI  - Equine parasite control under prescription-only conditions in Denmark--awareness,
      knowledge, perception, and strategies applied.
AB  - Due to widespread development of anthelmintic resistance in equine parasites,
      recommendations for their control are currently undergoing marked changes with a
      shift of emphasis toward more coprological surveillance and reduced treatment
      intensity. Denmark was the first nation to introduce prescription-only
      restrictions of anthelmintic drugs in 1999, but other European countries have
      implemented similar legislations over recent years. A questionnaire survey was
      performed in 2008 among Danish horse owners to provide a current status of
      practices and perceptions with relation to parasite control. Questions aimed at
      describing the current use of coprological surveillance and resulting
      anthelmintic treatment intensities, evaluating knowledge and perceptions about
      the importance of various attributes of parasite control, and assessing
      respondents' willingness to pay for advice and parasite surveillance services
      from their veterinarians. A total of 1060 respondents completed the
      questionnaire. A large majority of respondents (71.9%) were familiar with the
      concept of selective therapy. Results illustrated that the respondents' self
      evaluation of their knowledge about parasites and their control associated
      significantly with their level of interest in the topic and their type of
      education (P<0.0001). The large majority of respondents either dewormed their
      horses twice a year and/or performed two fecal egg counts per horse per year.
      This approach was almost equally pronounced in foals, horses aged 1-3 years old,
      and adult horses. The respondents rated prevention of parasitic disease and
      prevention of drug resistance as the most important attributes, while cost and
      frequent fecal testing were rated least important. Respondents' actual spending
      on parasite control per horse in the previous year correlated significantly with
      the amount they declared themselves willing to spend (P<0.0001). However, 44.4%
      declared themselves willing to pay more than what they were spending. Altogether,
      results indicate that respondents were generally familiar with equine parasites
      and the concept of selective therapy, although there was some confusion over the
      terms small and large strongyles. They used a large degree of fecal surveillance
      in all age groups, with a majority of respondents sampling and/or treating around
      twice a year. Finally, respondents appeared willing to spend money on parasite
      control for their horses. It is of concern that the survey suggested that foals
      and young horses are treated in a manner very similar to adult horses, which is
      against current recommendations. Thus, the survey illustrates the importance of
      clear communication of guidelines for equine parasite control. 

PMID- 24275445
TI  - Polyurethane and polyurea nanoparticles based on polyoxyethylene castor oil
      derivative surfactant suitable for endovascular applications.
AB  - The design of new, safe and effective nanotherapeutic systems is an important
      challenge for the researchers in the nanotechnology area. This study describes
      the formation of biocompatible polyurethane and polyurea nanoparticles based on
      polyoxyethylene castor oil derivative surfactant formed from O/W nano-emulsions
      by polymerization at the droplet interfaces in systems composed by aqueous
      solution/Kolliphor((r)) ELP/medium chain triglyceride suitable for intravenous
      administration. Initial nano-emulsions incorporating highly hydrophilic materials
      were prepared by the phase inversion composition (PIC) method. After
      polymerization, nanoparticles with a small particle diameter (25-55 nm) and low
      polydispersity index were obtained. Parameters such as concentration of monomer,
      O/S weight ratio as well as the polymerization temperature were crucial to
      achieve a correct formation of these nanoparticles. Moreover, FT-IR studies
      showed the full conversion of the monomer to polyurethane and polyurea polymers.
      Likewise the involvement of the surfactant in the polymerization process through
      their nucleophilic groups to form the polymeric matrix was demonstrated. This
      could mean a first step in the development of biocompatible systems formulated
      with polyoxyethylene castor oil derivative surfactants. In addition, haemolysis
      and cell viability assays evidenced the good biocompatibility of KELP
      polyurethane and polyurea nanoparticles thus indicating the potential of these
      nanosystems as promising drug carriers.

PMID- 24275446
TI  - PAMAM dendrimers as aerosol drug nanocarriers for pulmonary delivery via
      nebulization.
AB  - Polyamidoamine (PAMAM) dendrimers were evaluated as nanocarriers for pulmonary
      delivery of the model poorly soluble anti-asthma drug beclometasone dipropionate
      (BDP) using G3, G4 and G4(12) dendrimers. BDP-loaded dendrimers were
      characterized for drug solubility, in vitro drug release and aerosolization
      properties using three nebulizers: Pari LC Sprint (air-jet), Aeroneb Pro
      (actively vibrating-mesh) and Omron MicroAir (passively vibrating-mesh)
      nebulizers. Solubilization of BDP using dendrimers was increased by increasing
      the dendrimer generation and by using higher pH media. In vitro release studies
      showed that BDP when complexed with dendrimers exhibited a sustained release, and
      for all dendrimer formulations less than 35% of the drug was released after 8h.
      Nebulization studies revealed that aerosol performance was dependent on nebulizer
      rather than dendrimer generation. Nebulization output values for the Pari (air
      jet) and Aeroneb Pro (active mesh) nebulizers were in the range of 90-92% and 85
      89% respectively compared to 57-63% for the Omron (passive mesh) nebulizer. The
      size of the droplets generated from the jet nebulizer was slightly smaller and
      aerosol polydispersity was lower compared to both mesh devices. The "fine
      particle fraction (FPF)" of the aerosols was in the following order: Pari (air
      jet)>Aeroneb Pro (active mesh)>Omron (passive mesh). This study demonstrates that
      BDP-dendrimers have potential for pulmonary inhalation using air-jet and
      vibrating-mesh nebulizers. Moreover, the aerosol characteristics are influenced
      by nebulizer design rather than dendrimer generation. 

PMID- 24275447
TI  - Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a
      mechanistic study.
AB  - Liposomes containing bile salts (BS-liposomes) significantly enhanced the oral
      bioavailability of insulin (rhINS). However, the underlying absorption mechanisms
      have not been well understood yet. In this study, the transiting fate of the
      liposomes was first investigated using fluorescent imaging tools to confirm the
      effect of enhanced gastrointestinal stability. In order to obtain evidence of
      enhanced transcellular permeation, the interaction between BS-liposomes and the
      biomembrane was investigated in Caco-2 cell lines. BS-liposomes were found to be
      more stable in the gastrointestinal tract by showing prolonged residence time in
      comparison with conventional liposomes. BS-liposomes were significantly more
      effective for cellular uptake and transport of rhINS; and this effect was found
      to be size- and concentration-dependent. A good linear correlation was observed
      between the concentration of the liposomes and uptake/transport of rhINS.
      Confocal laser scanning microscopy visualization further validated the
      transcellular transit of BS-liposomes. The BS-liposomes showed little effect on
      cytotoxicity and did not induce apoptosis within 24h investigation. It was
      concluded that BS-liposomes showed improved in vivo residence time and enhanced
      permeation across the biomemebranes. Mechanisms of trans-enterocytic
      internalization could be proposed as an interpretation for enhanced absorption of
      insulin-loaded liposomes. 

PMID- 24275449
TI  - Design of cationic lipid nanoparticles for ocular delivery: development,
      characterization and cytotoxicity.
AB  - In the present study we have developed lipid nanoparticle (LN) dispersions based
      on a multiple emulsion technique for encapsulation of hydrophilic drugs or/and
      proteins by a full factorial design. In order to increase ocular retention time
      and mucoadhesion by electrostatic attraction, a cationic lipid, namely
      cetyltrimethylammonium bromide (CTAB), was added in the lipid matrix of the
      optimal LN dispersion obtained from the factorial design. There are a limited
      number of studies reporting the ideal concentration of cationic agents in LN for
      drug delivery. This paper suggests that the choice of the concentration of a
      cationic agent is critical when formulating a safe and stable LN. CTAB was
      included in the lipid matrix of LN, testing four different concentrations (0.25%,
      0.5%, 0.75%, or 1.0%wt) and how composition affects LN behavior regarding
      physical and chemical parameters, lipid crystallization and polymorphism, and
      stability of dispersion during storage. In order to develop a safe and compatible
      system for ocular delivery, CTAB-LN dispersions were exposed to Human
      retinoblastoma cell line Y-79. The toxicity testing of the CTAB-LN dispersions
      was a fundamental tool to find the best CTAB concentration for development of
      these cationic LN, which was found to be 0.5 wt% of CTAB.

PMID- 24275448
TI  - Gene delivery of PAMAM dendrimer conjugated with the nuclear localization signal
      peptide originated from fibroblast growth factor 3.
AB  - Polyamidoamine (PAMAM) is one of the widely employed non-viral vectors in gene
      therapy research, and shows excellent biocompatibility and relatively low
      cytotoxicity. However, it has poor transfection efficiency compared with that of
      polyethylenimine (PEI, 25 kDa). To enhance the gene expression efficiency, we
      introduced the RRRK peptide from mouse fibroblast growth factor 3 (FGF3) to
      PAMAM, which is a known nuclear localization signal (NLS). We synthesized PAMAM
      KRRR and PAMAM-RRRK to verify the difference of the induced functional status
      from reversal of the N-terminus. PAMAM containing the FGF3 peptide showed a
      transfection efficiency corresponding to that of PEI in HEK293, and HeLa cells,
      and showed much higher gene expression capacity than that of PEI in NIH3T3 cells
      with relatively decreased cytotoxicity. These results imply that introduction of
      the FGF 3 peptide has the potential to provide a novel PAMAM-based vector by
      enhancing its gene expression efficiency.

PMID- 24275450
TI  - The effects of suspension particle size on the performance of air-jet, ultrasonic
      and vibrating-mesh nebulisers.
AB  - Using latex microspheres as model suspensions, the influence of suspension
      particle size (1, 4.5 and 10 MUm) on the properties of aerosols produced using
      Pari LC Sprint (air-jet), Polygreen (ultrasonic), Aeroneb Pro (actively vibrating
      mesh) and Omron MicroAir NE-U22 (passively vibrating-mesh) nebulisers was
      investigated. The performance of the Pari nebuliser was independent of latex
      spheres particle size. For both Polygreen and Aeroneb Pro nebulizers, total
      aerosol output increased when the size of latex spheres increased, with highest
      fine particle fraction (FPF) values being recorded. However, following
      nebulisation of 1 or 4.5 MUm suspensions with the Polygreen device, no particles
      were detected in the aerosols deposited in a two-stage impinger, suggesting that
      the aerosols generated from this device consisted mainly of the continuous phase
      while the dispersed microspheres were excluded and remained in the nebuliser. The
      Omron nebuliser efficiently nebulised the 1 MUm latex spheres, with high output
      rate and no particle aggregation. However, this device functioned inefficiently
      when delivering 4.5 or 10 MUm suspensions, which was attributed to the mild
      vibrations of its mesh and/or the blockage of the mesh apertures by the
      microspheres. The Aeroneb Pro fragmented latex spheres into smaller particles,
      but uncontrolled aggregation occurred upon nebulisation. This study has shown
      that the design of the nebuliser influenced the aerosol properties using latex
      spheres as model suspensions. Moreover, for the recently marketed mesh
      nebulisers, the performance of the Aeroneb Pro device was less dependent on
      particle size of the suspension compared with the Omron MicroAir nebuliser.

PMID- 24275451
TI  - Travelling with HIV: a cross sectional analysis of Danish HIV-infected patients.
AB  - BACKGROUND: We aimed to describe travel patterns, extent of professional pre
      travel advice and health problems encountered during travel among HIV-infected
      individuals. METHODS: During a six-month period a questionnaire was handed out to
      2821 adult HIV-infected individuals attending any of the eight Danish medical HIV
      care centers. RESULTS: A total of 763 individuals responded. During the previous
      two years 49% had travelled outside Europe; 18% had travelled less and 30% were
      more cautious when choosing travel destination than before the HIV diagnosis. Pre
      travel advice was sought by only 38%, and travel insurance was taken out by 86%.
      However, 29%/74% did not inform the advisor/the insurance company about their HIV
      status. Nearly all patients on highly active antiretroviral therapy (HAART) were
      adherent, but 58% worried about carrying HIV-medicine and 19% tried to hide it.
      Only 19% experienced health problems during travel, 6% sought medical assistance
      and 0.5% was hospitalized. CONCLUSIONS: Danish HIV-infected patients travel
      frequently outside Denmark. Health and adherence to HAART were not major problems
      during travel. The main problems were failure to seek pre-travel advice, lack of
      disclosure of HIV status when seeking pre-travel advice or getting a travel
      insurance.

PMID- 24275453
TI  - Effects of respiratory muscle training on pulmonary functions in patients with
      slowly progressive neuromuscular disease: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of inspiratory and expiratory muscle
      training on pulmonary functions in patients with slowly progressive neuromuscular
      disease. DESIGN: Prospective randomized controlled double-blinded study. SETTING:
      Chest diseases clinic of university hospital. SUBJECTS: Twenty-six patients with
      slowly progressive neuromuscular disease followed for respiratory problems were
      included in the study. Patients were randomly divided into two groups;
      experimental (n = 14; age 31.6 +/-12.3 years) and sham (n = 12; age 26.5 +/-8.6
      years) groups. METHODS: Spirometry, peak cough flow, maximal inspiratory
      pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure were
      measured before the eighth week of study, and subsequently at end of it.
      Respiratory muscle training was performed by inspiratory (Threshold Inspiratory
      Muscle Trainer) and expiratory (Threshold Positive Expiratory Pressure) threshold
      loading methods. Training intensities were increased according to maximal
      inspiratory and expiratory pressures in the experimental group, while the lowest
      loads were used for training in the sham group. Patients performed 15 minutes
      inspiratory muscle training and 15 minutes expiratory muscle training, twice a
      day, five days/week, for a total of eight weeks at home. Training intensity was
      adjusted in the training group once a week. RESULTS: Maximal inspiratory and
      expiratory pressures (cmH2O, % predicted) (respectively p = 0.002, p = 0.003, p =
      0.04, p = 0.03) and sniff nasal inspiratory pressure (p = 0.04) were improved in
      the experimental group when compared with the sham group. However, there was no
      improvement in spirometric measurements when groups were compared (p > 0.05).
      CONCLUSIONS: As a conclusion of our study, we found that respiratory muscle
      strength improved by inspiratory and expiratory muscle training in patients with
      slowly progressive neuromuscular disease.

PMID- 24275452
TI  - Measuring complexity in neurological rehabilitation: the Oxford Case Complexity
      Assessment Measure (OCCAM).
AB  - OBJECTIVE: To investigate validity and reliability of a new measure of case
      complexity, the Oxford Case Complexity Assessment Measure (OCCAM). DESIGN: Data
      collection on inpatients and outpatients attending for rehabilitation. In
      subsets, repeat assessments were undertaken two weeks apart, by clinicians
      unaware of initial data, and on admission and on discharge from inpatient
      rehabilitation. SETTING: Specialist neurological rehabilitation service.
      SUBJECTS: Patients receiving rehabilitation after acute onset disability.
      INTERVENTIONS: Assessment by clinical staff as part of routine care. MEASURES:
      OCCAM, the INTERMED, Rehabilitation Complexity Scale - Extended (RCS-E), clinical
      judgement of complexity (0-10 numerical rating scale), length of stay and
      discharge destination (for inpatients). RESULTS: For the OCCAM, the Cronbach's
      alpha coefficient was 0.69 and item-total correlations were moderate to high
      except for pathology and time. The correlation coefficients with OCCAM were:
      INTERMED (rho = 0.694), RCS-E (rho = 0.736), and team judgement (rho = 0.796).
      Inter-rater agreement was excellent (Weighted kappa = 0.95). Correlation between
      admission and discharge scores was rho = 0.917. Test-retest agreement was good
      (intraclass correlation coefficient 0.86). Higher mean admission scores were
      associated with prolonged stays (38.6 +/- 12.2 versus 32.9 +/- 13.7, P = 0.04)
      and failure to return home (48.0 +/- 13.7 versus mean 32.1 +/- 10.7, P < 0.001).
      The optimal cut-off of OCCAM to detect patients not discharged home was >= 34,
      with corresponding sensitivity and specificity of 84.6% and 62.8%, respectively.
      CONCLUSIONS: This preliminary evidence suggests that the OCCAM may measure case
      complexity reliably, and may predict rehabilitation resource used and outcome.
      Further research is warranted.

PMID- 24275454
TI  - Standardization and quality control in proteomics.

PMID- 24275455
TI  - The ubiquitin ligase RNF126 regulates the retrograde sorting of the cation
      independent mannose 6-phosphate receptor.
AB  - The ubiquitin proteasome system is central to the regulation of a number of
      intracellular sorting pathways in mammalian cells including quality control at
      the endoplasmic reticulum and the internalization and endosomal sorting of cell
      surface receptors. Here we describe that RNF126, an E3 ubiquitin ligase, is
      involved in the sorting of the cation-independent mannose 6-phosphate receptor
      (CI-MPR). In cells transiently depleted of RNF126, the CI-MPR is dispersed into
      Rab4 positive endosomes and the efficiency of retrograde sorting is delayed.
      Furthermore, the stable knockdown of RNF126 leads to the lysosomal degradation of
      CI-MPR and missorting of cathepsin D. RNF126 specifically regulates the sorting
      of the CI-MPR as other cargo that follow the retrograde sorting route including
      the cholera toxin, furin and TGN38 are unaffected in the absence of RNF126.
      Lastly we show that the RING finger domain of RNF126 is required to rescue the
      decrease in CI-MPR levels, suggesting that the ubiquitin ligase activity of
      RNF126 is required for CI-MPR sorting. Together, our data indicate that the
      ubiquitin ligase RNF126 has a role in the retrograde sorting of the CI-MPR. 

PMID- 24275456
TI  - KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic
      cancer cells in vitro.
AB  - Pancreatic cancer is an aggressive malignancy and one of the leading causes of
      cancer deaths. The high mortality rate is mostly due to the lack of appropriate
      tools for early detection of the disease and a shortage of effective therapies.
      We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of
      the alpha karyopherin family of nuclear import receptors, is frequently amplified
      and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is
      absent in practically all normal human adult tissues but elevated in several
      pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T
      pancreatic cancer cells led to a reduction in cell growth and decreased anchorage
      independent growth, as well as increased autophagy. The cell growth effects were
      accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of
      the cell cycle. Interestingly, the p21 induction was caused by increased mRNA
      synthesis and not defective nuclear transport. These data strongly demonstrate
      that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells
      in vitro and thereby provide the first evidence on the functional role for KPNA7
      in human cancer. 

PMID- 24275457
TI  - Graphical evaluation of vocal fold vibratory patterns by high-speed
      videolaryngoscopy.
AB  - OBJECTIVE: To characterize the voice and vocal fold function of an individual, it
      is essential to evaluate vocal fold vibration. The most widely used method for
      this purpose has been videolaryngoscopy. METHODS: This article proposes a digital
      image processing algorithm to estimate the glottal area (ie, the space between
      the vocal folds) and produce graphs of the opening and closing phases of the
      glottal cycle. In eight subjects without voice disorders, vocal fold movements
      were recorded by high-speed videolaryngoscopy at 4000 frames per second. The
      video data were processed by a combination of image segmentation techniques that
      estimate the glottal area. The segmented area was used to construct the glottal
      waveform. RESULTS: The graphs revealed important properties of vocal fold
      vibration, including amplitude, velocity, and other characteristics that have a
      major influence on voice quality. CONCLUSIONS: The combination of the high-speed
      technology with the proposed method improves the vocal fold analysis given a
      numerical feedback through graphical representation of the real vibratory
      patterns of the folds.

PMID- 24275458
TI  - Voice change in end-stage renal disease patients after hemodialysis: correlation
      of subjective hoarseness and objective acoustic parameters.
AB  - INTRODUCTION: Patients with end-stage renal disease (ESRD) who are treated with
      hemodialysis (HD) frequently complain about hoarseness after completion of each
      HD session. The HD treatment affects laryngeal volume and muscle function. This
      study attempted to evaluate the vocal effect of HD by acoustic and aerodynamic
      analysis and to determine the difference between voice change group (VCG) and
      nonvoice change group (NVCG). MATERIALS AND METHODS: A total of 55 patients (34
      females and 21 males) diagnosed with ESRD and undergoing outpatient HD were
      enrolled. The subjects were divided into the VCG (n=13) and NVCG (n=42) by the
      change of the Korean Voice Handicap Index score. Patients underwent weighing and
      acoustic, aerodynamic analysis before and after the HD. Fundamental frequency
      (F0), jitter, shimmer, noise-to-harmonics ratio (NHR), pitch range, habitual
      pitch, voice energy, and maximal phonation time (MPT) were obtained. The pre- and
      post-HD data were compared using paired t test. The results were compared after
      dividing the total group into the VCG and NVCG categories. Correlation between
      the change of the weight and change of the voice analysis result was certified by
      Pearson correlation coefficient. RESULTS: The F0 and habitual pitch increased in
      all subjects. The NHR and MPT parameters significantly decreased (P<0.05). In the
      NVCG group, all the results were same as the total group. In the VCG group, the
      NHR result differed from the total group. All acoustic parameters showed no
      statistically significant differences between the two groups. There was no
      correlation between the weight change (%) and the change of acoustic parameter
      results. CONCLUSIONS: The NVCG group of patient displayed improvement in NHR,
      whereas the VCG group showed no change. Weight change did not significantly
      correlate with the voice analysis results.

PMID- 24275459
TI  - Correlation of otologic complaints in soldiers with speech disorders after
      traumatic brain injury.
AB  - OBJECTIVES/HYPOTHESIS: To determine the prevalence of otologic complaints in
      subjects with dysphonia and traumatic brain injury (TBI) in a sample population
      of the US Army. STUDY DESIGN: Cross-sectional study. METHODS: A total of 292
      subjects were identified with a new diagnosis of voice disorder during a 3.5-year
      period at three large military medical centers. Of them, 70 subjects were also
      identified with TBI and had no history of dysphonia before this time period. In
      those with voice disorders and TBI, documentation of hearing complaints, hearing
      loss, tinnitus, or vertigo was recorded. Time to visit an otolaryngologist and
      audiologist were also recorded. RESULTS: A total of 70 soldiers were identified
      with a diagnosis of a voice disorder and TBI. Of these soldiers, 83% had at least
      one otologic complaint and 50% had more than one. Approximately 60%, 39%, and 44%
      of the subjects reported tinnitus, hearing loss, or vertigo, respectively. A
      total of 62% of the subjects with otologic complaints, TBI, and dysphonia were
      seen by an otolaryngologist. Time until an otolaryngologist evaluated these
      soldiers varied widely, with an average of 17 months and standard deviation of
      12.5 months. CONCLUSIONS: Otologic manifestations are common in soldiers with
      dysphonia and TBI. Careful consideration of communication impairment from
      otologic dysfunction in those with speech disorders after TBI is warranted.

PMID- 24275460
TI  - Correlation among the dysphonia severity index (DSI), the RBH voice perceptual
      evaluation, and minimum glottal area in female patients with vocal fold nodules.
AB  - OBJECTIVES: To investigate the clinical significance and correlation of the
      dysphonia severity index (DSI), the RBH (roughness [R]; breathiness [B];
      hoarseness [H]) perceptual voice quality evaluation, and minimum glottal area
      (MGA) in patients with vocal fold nodules and validate the practicality of the
      DSI further. METHODS: The DSI evaluation, the voice RBH perceptual evaluation,
      and the MGA were performed on 30 female patients with vocal fold nodules (the
      patient group) and 30 female volunteers with normal voices (the control group).
      The DSI determination was calculated using the following formula: DSI = 0.13 *
      MPT + 0.0053 * F(0)-High - 0.26 * I-Low - 1.18 * Jitter(%) + 12.4. The RBH
      evaluation was graded according to four scales. The MGA was measured by KayPENTAX
      Kips (7105) software. The differences among the DSI, the RBH grade, and MGA of
      the patients were compared. RESULTS: The median DSI values of the patient group
      and the control group were -0.81 and 3.79, respectively, and the difference was
      statistically significant (P < 0.01). The median MGA of the patient group and the
      control group were 355.5 and 121, respectively, and the difference was
      statistically significant (P < 0.01). DSI exhibited moderate negative correlation
      with R (rP = -0.686, P < 0.01), B (rP = -0.609, P < 0.01), and H (rP = -0.487, P
      < 0.01). MGA demonstrated moderate positive correlation with R (rP = 0.667, P <
      0.01), B (rP = 0.545, P < 0.01), and H (rP = 0.449, P < 0.01), whereas MGA showed
      strong negative correlation with DSI (rP = -0.888, P < 0.01). CONCLUSIONS: The
      application of the DSI as an objective parameter to evaluate dysphonia in female
      patients with vocal nodules has significant clinical application and good
      correlation with MGA measurement.

PMID- 24275461
TI  - Stroboscopy in detection of laryngeal dysplasia effectiveness and limitations.
AB  - Vocal fold pathology changes the appearance and vibratory patterns observed
      during stroboscopic examination, but a strict correlation between the vibratory
      pattern and the dysplasia type does not exist. The aims of this study were to
      determine the role of stroboscopy in vocal fold dysplasia assessment and to
      determine whether stroboscopy is the deciding factor when performing
      laryngomicroscopy with biopsy in suspicious lesions. This prospective controlled
      study involved 112 patients with laryngeal dysplasia treated over a 2-year period
      at a tertiary medical center. Patient data and clinical, stroboscopy,
      laryngomicroscopy, and histopathologic reports were reviewed. During the
      stroboscopy, glottic occlusion, phase symmetry, periodicity, amplitude, mucosal
      wave, and nonvibratory segments were followed. Laryngomicroscopy with different
      types of endoscopic cordectomies (types I-III) was performed as a therapeutic
      measure, with a 12-month follow-up period. Nonvibrating segments were present in
      15.1% of the patients with mild dysplasia and in 38.5% of the patients with
      moderate dysplasia. In 45.5% of the patients with severe dysplasia (carcinoma in
      situ), nonvibrating segments were absent. The amplitude of vocal fold vibrations
      in patients with mild dysplasia (P=0.03) was a significant factor indicative of
      recurrent disease, but none of the stroboscopic signs was significant for the
      disease progression. Severe dysplasia can be related to both nonvibrating and
      vibrating vocal fold segments. Stroboscopy cannot be used reliably for
      classifying laryngeal dysplasia and may indicate the need to perform
      laryngomicroscopy with biopsy in suspicious vocal fold lesions. The warning
      factors for recurrence and progression of dysplasia are treatment modality,
      abnormal amplitude of vibration, and nonvibrating segment. 

PMID- 24275462
TI  - Clinical voice analysis of Carnatic singers.
AB  - BACKGROUND AND OBJECTIVE: Carnatic singing is a classical South Indian style of
      music that involves rigorous training to produce an "open throated" loud,
      predominantly low-pitched singing, embedded with vocal nuances in higher pitches.
      Voice problems in singers are not uncommon. The objective was to report the
      nature of voice problems and apply a routine protocol to assess the voice.
      METHODS: Forty-five trained performing singers (females: 36 and males: 9) who
      reported to a tertiary care hospital with voice problems underwent voice
      assessment. The study analyzed their problems and the clinical findings. RESULTS:
      Voice change, difficulty in singing higher pitches, and voice fatigue were major
      complaints. Most of the singers suffered laryngopharyngeal reflux that coexisted
      with muscle tension dysphonia and chronic laryngitis. Speaking voices were rated
      predominantly as "moderate deviation" on GRBAS (Grade, Rough, Breathy, Asthenia,
      and Strain). Maximum phonation time ranged from 4 to 29 seconds (females: 10.2,
      standard deviation [SD]: 5.28 and males: 15.7, SD: 5.79). Singing frequency range
      was reduced (females: 21.3 Semitones and males: 23.99 Semitones). Dysphonia
      severity index (DSI) scores ranged from -3.5 to 4.91 (females: 0.075 and males:
      0.64). Singing frequency range and DSI did not show significant difference
      between sex and across clinical diagnosis. Self-perception using voice disorder
      outcome profile revealed overall severity score of 5.1 (SD: 2.7). Findings are
      discussed from a clinical intervention perspective. CONCLUSIONS: Study
      highlighted the nature of voice problems (hyperfunctional) and required
      modifications in assessment protocol for Carnatic singers. Need for regular
      assessments and vocal hygiene education to maintain good vocal health are
      emphasized as outcomes.

PMID- 24275468
TI  - Corticotropin-releasing factor-like peptide modifies the AMPA-, NMDA-dependent
      and GABAB-ergic properties of synaptic transmissions in vitro.
AB  - The aim of this study was to investigate the neurotrophic effects of the mystixin
      7 mini-peptide (MTX, a synthetic corticotrophin-releasing-factor-like peptide
      like peptide) using a slice-based system. The technique on-line monitoring of
      electrophysiological parameters (excitatory glutamatergic AMPAR-, NMDAR-dependent
      and inhibitory GABAB-ergic postsynaptic mechanisms) in the olfactory cortex
      slices of the rat brain exposed to varied amounts of MTX was used. MTX in a dose
      dependent manner inhibited both the AMPAR- and NMDAR-mediated postsynaptic
      processes. The peptide caused depression of inhibitory GABAB-ergic processes only
      at low doses of MTX (10, 25, 50 mg/mL) while at higher doses (100, 250 mg/mL) it
      enhanced them. These effects of MTX were reversible. AMPA-dependent (but not NMDA
      mediated mechanisms) and inhibitory processes were restored after washing. Triple
      reperfusion of slices with MTX (100 mg/mL) accelerated the inhibitory processes
      and induced NMDAR desensitization. MTX evoked the long-term depression on theta
      burst stimulation of the slices. This study did not only lead to the conclusion
      that the functions of the MTX mini-peptide is not limited to anti-inflammatory
      effects, but also is included modifications of excitatory glutamatergic AMPAR-,
      NMDAR-dependent and inhibitory GABAB-ergic postsynaptic mechanisms.

PMID- 24275469
TI  - Simultaneous removal of sulfide, nitrate and acetate under denitrifying sulfide
      removal condition: modeling and experimental validation.
AB  - Simultaneous removal of sulfide (S(2-)), nitrate (NO3(-)) and acetate (Ac(-))
      under denitrifying sulfide removal process (DSR) is a novel biological wastewater
      treatment process. This work developed a mathematical model to describe the
      kinetic behavior of sulfur-nitrogen-carbon and interactions between autotrophic
      denitrifiers and heterotrophic denitrifiers. The kinetic parameters of the model
      were estimated via data fitting considering the effects of initial S(2-)
      concentration, S(2-)/NO3(-)-N ratio and Ac(-)-C/NO3(-)-N ratio. Simulation
      supported that the heterotrophic denitratation step (NO3(-) reduction to NO2(-))
      was inhibited by S(2-) compared with the denitritation step (NO2(-) reduction to
      N2). Also, the S(2-) oxidation by autotrophic denitrifiers was shown two times
      lower in rate with NO2(-) as electron acceptor than that with NO3(-) as electron
      acceptor. NO3(-) reduction by autotrophic denitrifiers occurs 3-10 times slower
      when S(0) participates as final electron donor compared to the S(2-)-driven
      pathway. Model simulation on continuous-flow DSR reactor suggested that the
      adjustment of hydraulic retention time is an efficient way to make the reactor
      tolerating high S(2-) loadings. The proposed model properly described the kinetic
      behaviors of DSR processes over wide parametric ranges and which can offer
      engineers with basis to optimize bioreactor operation to improve the treatment
      capacity. 

PMID- 24275471
TI  - Toxicity assessment of size-fractionated urban road dust using ostracod
      Heterocypris incongruens direct contact test.
AB  - Urban road dusts (URDs, n=10) were collected from arterial, residential, parking
      area in highway and highway roads in and around Tokyo, Japan, to characterize
      toxicity of size-fractions by the ostracod Heterocypris incongruens direct
      contact test. The URDs were collected with vacuum cleaner and highway sweeping
      vehicles, dried and size-fractionated before conducting toxicity test. The LC20
      and LC50 of URDs varied (v/v) from 1.6 to 49%, and 3.8 to 67% respectively.
      Cluster analysis of URDs based on the concentration of heavy metal and PAHs
      standardized with the organic matter content was able to differentiate URDs into
      two groups, one group of higher toxicity and the other group of medium and lower
      toxicity. Mortality of ostracod decreased for some of the URDs when holding time
      of URD-water mixture was changed from 1h to 24h prior to the toxicity test.
      Fraction of fine particles was not always more toxic than the other fractions of
      coarse and medium particles. Site specific differences in toxicity of size
      fractionated URDs indicated the complexity in defining URD toxicity as there
      could be co-existence of various non-targeted toxicants. 

PMID- 24275470
TI  - Methyl parathion imprinted polymer nanoshell coated on the magnetic nanocore for
      selective recognition and fast adsorption and separation in soils.
AB  - Core-shell magnetic methyl parathion (MP) imprinted polymers (Fe3O4@MPIPs) were
      fabricated by a layer-by-layer self-assembly process. In order to take full
      advantage of the synergistic effect of hydrogen-binding interactions and pi-pi
      accumulation between host and guest for molecular recognition, methacrylic acid
      and 4-vinyl pyridine were chosen as co-functional monomers and their optimal
      proportion were investigated. The core-shell and crystalline structure,
      morphology and magnetic properties of Fe3O4@MPIPs were characterized. The MP
      imprinted nanoshell was almost uniform and about 100nm thick. Binding experiments
      demonstrated that Fe3O4@MPIPs possessed excellent binding properties, including
      high adsorption capacity and specific recognition, as well as fast adsorption
      kinetics and a fast phase separation rate. The equilibration adsorption capacity
      reached up to 9.1mg/g, which was 12 times higher than that of magnetic non
      imprinted polymers, while adsorption reached equilibrium within 5min at a
      concentration of 0.2mmol/L. Furthermore, Fe3O4@MPIPs successfully provided
      selective separation and removal of MP in soils with a recovery and detection
      limit of 81.1-87.0% and 5.2ng/g, respectively. 

PMID- 24275472
TI  - Mercury removal from water streams through the ion exchange membrane bioreactor
      concept.
AB  - Mercury is a highly toxic heavy metal that causes human health problems and
      environmental contamination. In this study, an ion exchange membrane bioreactor
      (IEMB) process was developed to achieve Hg(II) removal from drinking water and
      industrial effluents. Hg(II) transport through a cation exchange membrane was
      coupled with its bioreduction to Hg(0) in order to achieve Hg removal from
      concentrated streams, with minimal production of contaminated by-products
      observed. This study involves (1) membrane selection, (2) demonstration of
      process effectiveness for removing Hg from drinking water to below the 1ppb
      recommended limit, and (3) process application for treatment of concentrated
      water streams, where >98% of the Hg was removed, and the throughput of
      contaminated water was optimised through membrane pre-treatment. The IEMB process
      represents a novel mercury treatment technology with minimal generation of
      contaminated waste, thereby reducing the overall environmental impact of the
      process. 

PMID- 24275473
TI  - Preparation and characterization of Pd doped ceria-ZnO nanocomposite catalyst for
      methyl tert-butyl ether (MTBE) photodegradation.
AB  - A series of binary oxide catalysts (ceria-ZnO) were prepared and doped with
      different amounts of palladium in the range of 0.5%-1.5%. The prepared catalysts
      were characterized by SEM, TEM, XRD and XPS, as well as by N2 sorptiometry study.
      The XPS results confirmed the structure of the Pd CeO2-x-ZnO. The photocatalytic
      activity of these catalysts was evaluated for degradation of MTBE in water. These
      photocatalyst efficiently degrade a 100ppm aqueous solution of MTBE upon UV
      irradiation for 5h in the presence of 100mg of each of these photocatalysts. The
      removal of 99.6% of the MTBE was achieved with the ceria-ZnO catalyst doped with
      1% Pd. In addition to the Pd loading, the N2 sorptiometry study introduced other
      factors that might affect the catalytic efficiency is the catalyst average pore
      sizes. The photoreaction was determined to be a first order reaction. 

PMID- 24275474
TI  - Nanocrystalline ZnCO3-A novel sorbent for low-temperature removal of H2S.
AB  - The reactivity of a nanocrystalline ZnCO3 toward H2S (0.2vol% in N2/H2 mixture)
      at 140-180 degrees C was characterized by thermal gravimetric analysis and by
      breakthrough curves measurements. We have found that under used conditions
      transformation of ZnCO3 into ZnS is complete and the rate determining step of the
      sulfidation is the surface reaction. Such behavior is in strike contrast with
      that of ZnO whose sulfidation is severely limited by diffusion. The higher
      reactivity of ZnCO3 in comparison with ZnO is attributed to the different
      microstructure of ZnS layer formed in these materials after a partial
      sulfidation. As in ZnO-ZnS transformation the molar volume increases (from 14.5
      to 23.8cm(3)/mol), a continuous protective ZnS layer is formed hampering the
      access of H2S to the non reacted ZnO core. By contrast, in ZnCO3-ZnS
      transformation the molar volume decreases (from 27.9 to 23.8cm(3)/mol), which
      produces a discontinuous non-protective ZnS layer enabling a complete
      transformation of ZnCO3 even at 140 degrees C. The higher reactivity of ZnCO3
      results in a considerable increase of the breakthrough sulfur capacity of the
      carbonate in comparison with oxide. The material has therefore a good potential
      for being used as a disposable sorbent for H2S capture at low temperature. 

PMID- 24275475
TI  - Determination of arsenate in water by anion selective membrane electrode using
      polyurethane-silica gel fibrous anion exchanger composite.
AB  - Polyurethane (PU)-silica (Si gel) based fibrous anion exchanger composites were
      prepared by solid-gel polymerization of polyurethane in the presence of different
      amounts of silica gel. The formation of PU-Si gel fibrous anion exchanger
      composite was characterized by Fourier transform infra-red spectroscopy (FTIR), X
      ray diffraction (XRD), thermogravimetric analysis (TGA-DTA), scanning electron
      microscopy (SEM) and elemental analysis. The membrane having a composition of 5:3
      (PU:Si gel) shows best results for water content, porosity, thickness and
      swelling. Our studies show that the present ion selective membrane electrode is
      selective for arsenic, having detection limit (1*10(-8)M to 1*10(-1)M), response
      time (45s) and working pH range (5-8). The selectivity coefficient values for
      interfering ions indicate good selectivity for arsenate (AsO4(3-)) over
      interfering anions. The accuracy of the detection limit results was compared by
      PCA-Arsenomat. 

PMID- 24275476
TI  - Foliar exposure of the crop Lactuca sativa to silver nanoparticles: evidence for
      internalization and changes in Ag speciation.
AB  - The impact of engineered nanomaterials on plants, which act as a major point of
      entry of contaminants into trophic chains, is little documented. The foliar
      pathway is even less known than the soil-root pathway. However, significant
      inputs of nanoparticles (NPs) on plant foliage may be expected due to deposition
      of atmospheric particles or application of NP-containing pesticides. The uptake
      of Ag-NPs in the crop species Lactuca sativa after foliar exposure and their
      possible biotransformation and phytotoxic effects were studied. In addition to
      chemical analyses and ecotoxicological tests, micro X-ray fluorescence, micro X
      ray absorption spectroscopy, time of flight secondary ion mass spectrometry and
      electron microscopy were used to localize and determine the speciation of Ag at
      sub-micrometer resolution. Although no sign of phytotoxicity was observed, Ag was
      effectively trapped on lettuce leaves and a thorough washing did not decrease Ag
      content significantly. We provide first evidence for the entrapment of Ag-NPs by
      the cuticle and penetration in the leaf tissue through stomata, for the diffusion
      of Ag in leaf tissues, and oxidation of Ag-NPs and complexation of Ag(+) by thiol
      containing molecules. Such type of information is crucial for better assessing
      the risk associated to Ag-NP containing products. 

PMID- 24275477
TI  - Tick-borne encephalitis virus in ticks detached from humans and follow-up of
      serological and clinical response.
AB  - The risk of tick-borne encephalitis virus (TBEV) infection after a tick bite
      remains largely unknown. To address this, we investigated the presence of TBEV in
      ticks detached from humans in an attempt to relate viral copy number, TBEV
      subtype, and tick feeding time with the serological and clinical response of the
      tick-bitten participants. Ticks, blood samples, and questionnaires were collected
      from tick-bitten humans at 34 primary health care centers in Sweden and in the
      Aland Islands (Finland). A total of 2167 ticks was received from 1886 persons in
      2008-2009. Using a multiplex quantitative real-time PCR, 5 TBEV-infected ticks
      were found (overall prevalence 0.23%, copy range <4*10(2)-7.7*10(6)per tick). One
      unvaccinated person bitten by a tick containing 7.7*10(6) TBEV copies experienced
      symptoms. Another unvaccinated person bitten by a tick containing 1.8*10(3) TBEV
      copies developed neither symptoms nor TBEV antibodies. The remaining 3 persons
      were protected by vaccination. In contrast, despite lack of TBEV in the detached
      ticks, 2 persons developed antibodies against TBEV, one of whom reported
      symptoms. Overall, a low risk of TBEV infection was observed, and too few persons
      got bitten by TBEV-infected ticks to draw certain conclusions regarding the
      clinical outcome in relation to the duration of the blood meal and virus copy
      number. However, this study indicates that an antibody response may develop
      without clinical symptoms, that a bite by an infected tick not always leads to an
      antibody response or clinical symptoms, and a possible correlation between virus
      load and tick feeding time. 

PMID- 24275478
TI  - Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell
      nanoparticles induce long-lasting CD8(+) T cell responses in mice.
AB  - Distributed and on-demand vaccine production could be game-changing for
      infectious disease treatment in the developing world by providing new therapeutic
      opportunities and breaking the refrigeration "cold chain". Here, we show that a
      fusion protein between a calcium phosphate binding domain and the model antigen
      ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting
      50 nm calcium phosphate core-immunogen shell particles are comparable to soluble
      protein in inducing ovalbumin-specific antibody response and class switch
      recombination in mice. However, single dose vaccination with nanoparticles leads
      to higher expansion of ovalbumin-specific CD8(+) T cells upon challenge with an
      influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells
      produce high levels of IFN-gamma. Furthermore, mice exhibit a robust antigen
      specific CD8(+) T cell recall response when challenged with virus 8 months post
      immunization. These results underscore the promise of immunogen-controlled
      adjuvant mineralization for just-in-time manufacturing of effective T cell
      vaccines. FROM THE CLINICAL EDITOR: This paper reports that a fusion protein
      between a calcium phosphate binding domain and the model antigen ovalbumin can
      mineralize into a biocompatible adjuvant in a single step, enabling distributed
      and on-demand vaccine production and eliminating the need for refrigeration of
      vaccines. The findings highlight the possibility of immunogen-controlled adjuvant
      mineralization for just-in-time manufacturing of effective T cell vaccines.

PMID- 24275479
TI  - Fear acquisition and extinction in offspring of mothers with anxiety and
      depressive disorders.
AB  - Maternal anxiety and depression are significant risk factors for the development
      of these disorders in offspring. The pathways through which risk is conferred
      remain unclear. This study examined fear acquisition and extinction in 26
      children at high risk for emotional disorders by virtue of maternal
      psychopathology (n=14 with a mother with a principal anxiety disorder and n=12
      with a mother with a principal unipolar depressive disorder) and 31 low risk
      controls using a discriminative Pavlovian conditioning procedure. Participants,
      aged between 7 and 14 years, completed 16 trials of discriminative conditioning
      of two geometric figures, with (CS+) and without (CS-) an aversive tone (US),
      followed by 8 extinction trials (4*CS+, 4*CS-). In the context of comparable
      discriminative conditioning, children of anxious mothers showed larger skin
      conductance responses during extinction to the CS+ compared to the CS-, and to
      both CSs from the first to the second block of extinction trials, in comparison
      with low risk controls. Compared to low risk controls, children of depressed
      mothers showed smaller skin conductance responses to the CS+ than the CS- during
      acquisition. These findings suggest distinct psychophysiological premorbid risk
      markers in offspring of anxious and depressed mothers. 

PMID- 24275480
TI  - Predicting body fat percentage based on gender, age and BMI by using artificial
      neural networks.
AB  - In the human body, the relation between fat and fat-free mass (muscles, bones
      etc.) is necessary for the diagnosis of obesity and prediction of its
      comorbidities. Numerous formulas, such as Deurenberg et al., Gallagher et al.,
      Jackson and Pollock, Jackson et al. etc., are available to predict body fat
      percentage (BF%) from gender (GEN), age (AGE) and body mass index (BMI). These
      formulas are all fairly similar and widely applicable, since they provide an
      easy, low-cost and non-invasive prediction of BF%. This paper presents a program
      solution for predicting BF% based on artificial neural network (ANN). ANN
      training, validation and testing are done by randomly divided dataset that
      includes 2755 subjects: 1332 women (GEN = 0) and 1423 men (GEN = 1), with AGE
      from 18 to 88 y and BMI from 16.60 to 64.60 kg/m(2). BF% was estimated by using
      Tanita bioelectrical impedance measurements (Tanita Corporation, Tokyo, Japan).
      ANN inputs are: GEN, AGE and BMI, and output is BF%. The predictive accuracy of
      our solution is 80.43%. The main goal of this paper is to promote a new approach
      to predicting BF% that has same complexity and costs but higher predictive
      accuracy than above-mentioned formulas.

PMID- 24275481
TI  - Common maxillofacial terminology: do our patients understand what we say?
AB  - For a patient to make appropriate, informed decisions regarding their medical
      care, it is vital that the information given to them is complete and
      comprehensible. We have investigated patients' understanding of commonly used
      terms in an oral and maxillofacial clinic. To the authors' knowledge, this
      pertinent subject has not previously been explored for this specialty. METHOD:
      Patients were recruited for this questionnaire-based study in the oral and
      maxillofacial department out-patient clinics. The questionnaire includes multiple
      choice questions and 'free text' answers. RESULTS: All patients were invited to
      participate and we have shown the results of the 100 consecutive patients who
      agreed to take part. The 100 patients recruited ranged between the ages of 16 and
      75. English was the first language for 76 participants. The term 'mandible' was
      correctly defined by 37 respondents. Sixty per cent of patients' think that a
      fracture is a 'crack' and less severe than a broken bone. CONCLUSION: Common
      maxillofacial jargon can easily be misunderstood by patients. It is essential
      that all clinicians appropriately modify their language during consultations in
      order to deliver information in a comprehensive manner, to educate patients on
      their condition and to ensure sensible decision making by patients.

PMID- 24275482
TI  - Silver nitrate cauterization: a treatment option for aphthous stomatitis.
AB  - OBJECTIVES: In this study we compared silver nitrate cautery with placebo to
      assess the effect of silver nitrate cautery in aphthous stomatitis for pain
      relief and healing time. MATERIAL AND METHODS: In this study, sixty-five patients
      with aphthous stomatitis were assessed. Silver nitrate sticks were used in group
      A (treatment group) and placebo sticks were used for group B (control group).
      Change in the severity of pain, change in the size of the ulcers, healing time,
      side effects of the procedure were assessed. RESULTS: Although the mean value of
      pain scores before the procedure was similar in both of the groups, there were
      statistically significant differences between two groups after the procedure on
      the first to the seventh day. On the seventh day after the procedure, the ulcers
      were completely reepithelialized in 21 patients (60%) in the treatment group and
      in 10 patients (32%) in the placebo group. The difference was statistically
      significant (p < 0.01). In the treatment group, the mean healing time of ulcers,
      reported by these 21 patients, was 2.7 days (range 2-4) after the procedure. In
      the placebo group, the mean healing time of ulcers, reported by 10 patients with
      healed ulcers, was 5.5 days (range 4-7) after the procedure. The difference was
      statistically significant (p < 0.01). No side effects were recorded in either of
      the groups. CONCLUSION: In conclusion, silver nitrate cautery appears to be an
      effective and rapid treatment option for pain relief in aphthous stomatitis. Also
      this treatment shortens the healing time of ulcers.

PMID- 24275483
TI  - Different vaccination strategies in Spain and its impact on severe varicella and
      zoster.
AB  - Varicella vaccines available in Spain were marketed in 1998 and 2003 for non
      routine use. Since 2006 some regions decided to include varicella vaccination in
      their regional routine vaccination programmes at 15-18 months of age. Other
      regions chose the strategy of vaccinating susceptible adolescents. This study
      shows the trends in severe varicella zoster virus infections through the analysis
      of the hospital discharges related to varicella and herpes zoster in the general
      population from 2005 to 2010 in Spain. A total of 11,125 hospital discharges
      related to varicella and 27,736 related to herpes zoster were reported during the
      study period. The overall annual rate of hospitalization was 4.14 cases per
      100,000 for varicella and 10.33 cases per 100,000 for herpes zoster. In children
      younger than 5 years old varicella hospitalization rate significantly decreased
      from 46.77 in 2005 to 26.55 per 100,000 in 2010. The hospitalization rate related
      to herpes zoster slightly increased from 9.71 in 2005 to 10.90 per 100,000 in
      2010. This increase was mainly due to the significant increase occurring in the
      >84 age group, from 69.55 to 97.68 per 100,000. When gathering for regions taking
      into account varicella vaccine strategy, varicella related hospitalizations
      decreased significantly more in those regions which included the vaccine at 15-18
      months of age as a routine vaccine comparing with those vaccinating at 10-14
      years old. No significant differences were found in herpes zoster hospitalization
      rates regarding the varicella vaccination strategy among regions. Severe
      varicella infections decreased after implementation of varicella vaccination in
      Spain. This decrease was significantly higher in regions including the vaccine at
      15-18 months of age compared with those vaccinating susceptible adolescents. 

PMID- 24275484
TI  - A charge-optimized many-body potential for the U-UO2-O2 system.
AB  - Building on previous charge-optimized many-body (COMB) potentials for metallic
      alpha-U and gaseous O2, we have developed a new potential for UO2, which also
      allows the simulation of U-UO2-O2 systems. The UO2 lattice parameter, elastic
      constants and formation energies of stoichiometric and non-stoichiometric
      intrinsic defects are well reproduced. Moreover, this is the first rigid-ion
      potential that produces the correct deviation of the Cauchy relation, as well as
      the first classical interatomic potential that is able to determine the defect
      energies of non-stoichiometric intrinsic point defects in UO2 with an appropriate
      reference state. The oxygen molecule interstitial in the alpha-U structure is
      shown to decompose, with some U-O bonds approaching the natural bond length of
      perfect UO2. Finally, we demonstrate the capability of this COMB potential to
      simulate a complex system by performing a simulation of the alpha-U + O2 -> UO2
      phase transformation. We also identify a possible mechanism for uranium oxidation
      and the orientation of the resulting fluorite UO2 structure relative to the
      coordinate system of orthorhombic alpha-U. 

PMID- 24275485
TI  - Hollow fibre cell fishing with high performance liquid chromatography for
      screening bioactive anthraquinones from traditional Chinese medicines.
AB  - Hollow fibre cell fishing with high performance liquid chromatography (HFCF-HPLC)
      is a newly developed method used to screen and fish bioactive compounds in
      traditional Chinese medicines (TCMs). In the study, colorectal cancer cell HCT116
      was first seeded in a hollow fibre and used for screening and fishing active
      compounds from TCMs. The surface properties of the hollow fibre seeded with
      HCT116 cells, the non-specific binding between active centres in the fibre and
      the target compounds, the cell survival rate under different conditions before
      and after screening, the repeatability and recovery of HFCF-HPLC were
      investigated in detail. The cell fishing factor of active compound was defined in
      HFCF-HPLC. We employed HFCF-HPLC to screen and fish anthraquinones active
      compounds group from extracts of Polygonum cuspidatum, Cecropia obtusifolia L.
      and Polygoni multiflori radix praeparata. Some of the anthraquinones structures
      screened from TCMs were identified by comparing to the retention time of the
      reference substances confirmed by mass spectrometry. The ability of permeable
      membrane of anthraquinones screened by HFCF-HPLC was further described.
      Indomethacin was used as the positive control substance. Results demonstrated
      that HFCF-HPLC is an effective, stable and reliable method to screen and analyse
      bioactive compounds. Other bioactive compounds from TCMs could also be screened. 

PMID- 24275486
TI  - Minimizing adsorption of histidine-tagged proteins for the study of protein
      deoxyribonucleic acid interactions by kinetic capillary electrophoresis.
AB  - Affinity interactions between DNA and proteins play a crucial role in many
      cellular processes. Kinetic Capillary Electrophoresis is a highly efficient tool
      for kinetic and equilibrium studies of protein-DNA interactions. Recombinant
      proteins, which are typically used for in vitro studies of protein-DNA
      interactions, are often expressed with a His tag to aid in their purification. In
      this work, we study how His tags affect Kinetic Capillary Electrophoresis
      analysis of protein-DNA interactions. We found that the addition of a His tag can
      increase or decrease protein adsorption to a bare-silica capillary wall,
      dependent on the protein. For Kinetic Capillary Electrophoresis measurements, it
      is essential to have as little protein adsorption as possible. We screened a
      number of capillary coatings to reduce adsorption of the His-tagged DNA mismatch
      repair protein MutS to the capillary wall and found that UltraTrol LN was the
      most effective coating. The effectiveness of the coating was confirmed with the
      prevention of adsorption of His-tagged fat mass and obesity-associated protein.
      Under typical conditions, the coating reduced protein adsorption to a level at
      which accurate Kinetic Capillary Electrophoresis analysis of protein-DNA
      interactions was possible. We further used Kinetic Capillary Electrophoresis to
      study how the His tag affected Kd of protein-DNA interactions for the MutS
      protein. Using UltraTrol LN, we found that the effect of the His tag was
      insignificant. 

PMID- 24275487
TI  - Illicit and abused drugs in sewage sludge: method optimization and occurrence.
AB  - A sensitive and reliable method for the determination of 20 abused and illicit
      drugs and their metabolites in sewage sludge has been developed and validated. To
      the authors' knowledge, nine out of the 20 selected analytes, namely,
      cocaethylene, ephedrine, heroin, alprazolam, lysergic acid diethylamide (LSD),
      its metabolite 2-oxo-3-hydroxy-LSD, and the cannabinoids Delta(9)
      tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), are
      investigated for the first time in this matrix. In the optimized approach, freeze
      dried sewage sludge samples were extracted by means of pressurized liquid
      extraction, and the extracts were further cleaned-up by solid phase extraction.
      Analytes were determined by liquid chromatography coupled to tandem mass
      spectrometry. Method limits of quantification were below 3.3ng/g d.w. for all
      compounds but cannabinoids (8.2-22.5ng/g d.w.). Method repeatability was below
      14% for most compounds. Overall method recoveries were low due to the presence of
      matrix interferences that could not be completely eliminated and suppressed the
      ionization of the target analytes between 26% and 89%. However, extraction losses
      and matrix effects were satisfactorily corrected through the use of isotopically
      labeled analogs as surrogate standards, ensuring reliable results. The method was
      applied to the analysis of various sewage sludge samples. Cannabinoids, methadone
      and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were
      the most ubiquitous and abundant compounds, showing maximum concentrations above
      100ng/g d.w. in all cases (up to 579ng/g d.w. in the case of THC). This work is
      the first evidence of the presence of the cannabinoids CBN, CBD, and THC in
      sewage sludge. 

PMID- 24275488
TI  - Risk factors affecting chronic rupture of the plantar fascia.
AB  - BACKGROUND: Prior to 1994, plantar fascia ruptures were considered as an acute
      injury that occurred primarily in athletes. However, plantar fascia ruptures have
      recently been reported in the setting of preexisting plantar fasciitis. We
      analyzed risk factors causing plantar fascia rupture in the presence of
      preexisting plantar fasciitis. METHODS: We retrospectively reviewed 286 patients
      with plantar fasciitis who were referred from private clinics between March 2004
      and February 2008. Patients were divided into those with or without a plantar
      fascia rupture. There were 35 patients in the rupture group and 251 in the
      nonrupture group. The clinical characteristics and risk factors for plantar
      fascia rupture were compared between the 2 groups. We compared age, gender, the
      affected site, visual analog scale pain score, previous treatment regimen, body
      mass index, degree of ankle dorsiflexion, the use of steroid injections, the
      extent of activity, calcaneal pitch angle, the presence of a calcaneal spur, and
      heel alignment between the 2 groups. RESULTS: Of the assessed risk factors, only
      steroid injection was associated with the occurrence of a plantar fascia rupture.
      Among the 35 patients with a rupture, 33 had received steroid injections. The
      odds ratio of steroid injection was 33. CONCLUSION: Steroid injections for
      plantar fasciitis should be cautiously administered because of the higher risk
      for plantar fascia rupture. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study.

PMID- 24275489
TI  - Immunology on chip: promises and opportunities.
AB  - Microfluidics has facilitated immunological studies by enhancing speed,
      efficiency and sensitivity of current analysis methods. It offers miniaturization
      of current laboratory equipment, and enables analysis of clinical samples without
      the need for sophisticated infrastructure. More importantly, microfluidics offers
      unique capabilities; including conducting multiple serial or parallel tasks as
      well as providing complex and precisely controlled environmental conditions that
      are not achievable using conventional laboratory equipment. Microfluidics is a
      promising technology for fundamental and applied immunological studies, allowing
      generation of high throughput, robust and portable platforms, opening a new area
      of automation in immunology. 

PMID- 24275490
TI  - The biophysical and biochemical properties of the autoimmune regulator (AIRE)
      protein.
AB  - AIRE (for autoimmune regulator) is a multidomain protein that performs a
      fundamental function in the thymus and possibly in the secondary lymphoid organs:
      the regulation, especially in the sense of activation, of the process of gene
      transcription in cell lines deputed to the presentation of self-antigens to the
      maturing T lymphocytes. The apoptosis of the elements bearing T-cell receptors
      with critical affinity for the exhibited self-antigens prevents the escape of
      autoreactive clones and represents a simple and efficient mechanism of deletional
      self-tolerance. However, AIRE action relies on an articulated complex of
      biophysical and biochemical properties, in most cases attributable to single
      subspecialized domains. Here a thorough review of the matter is presented, with a
      privileged look at the pathogenic changes of AIRE that interfere with such
      properties and lead to the impairment in its chief function. 

PMID- 24275491
TI  - PhylomeDB v4: zooming into the plurality of evolutionary histories of a genome.
AB  - Phylogenetic trees representing the evolutionary relationships of homologous
      genes are the entry point for many evolutionary analyses. For instance, the use
      of a phylogenetic tree can aid in the inference of orthology and paralogy
      relationships, and in the detection of relevant evolutionary events such as gene
      family expansions and contractions, horizontal gene transfer, recombination or
      incomplete lineage sorting. Similarly, given the plurality of evolutionary
      histories among genes encoded in a given genome, there is a need for the combined
      analysis of genome-wide collections of phylogenetic trees (phylomes). Here, we
      introduce a new release of PhylomeDB (http://phylomedb.org), a public repository
      of phylomes. Currently, PhylomeDB hosts 120 public phylomes, comprising >1.5
      million maximum likelihood trees and multiple sequence alignments. In the current
      release, phylogenetic trees are annotated with taxonomic, protein-domain
      arrangement, functional and evolutionary information. PhylomeDB is also a major
      source for phylogeny-based predictions of orthology and paralogy, covering >10
      million proteins across 1059 sequenced species. Here we describe newly
      implemented PhylomeDB features, and discuss a benchmark of the orthology
      predictions provided by the database, the impact of proteome updates and the use
      of the phylome approach in the analysis of newly sequenced genomes and
      transcriptomes. 

PMID- 24275492
TI  - Structural determinants of DNA recognition by plant MADS-domain transcription
      factors.
AB  - Plant MADS-domain transcription factors act as key regulators of many
      developmental processes. Despite the wealth of information that exists about
      these factors, the mechanisms by which they recognize their cognate DNA-binding
      site, called CArG-box (consensus CCW6GG), and how different MADS-domain proteins
      achieve DNA-binding specificity, are still largely unknown. We used information
      from in vivo ChIP-seq experiments, in vitro DNA-binding data and evolutionary
      conservation to address these important questions. We found that structural
      characteristics of the DNA play an important role in the DNA binding of plant
      MADS-domain proteins. The central region of the CArG-box largely resembles a
      structural motif called 'A-tract', which is characterized by a narrow minor
      groove and may assist bending of the DNA by MADS-domain proteins. Periodically
      spaced A-tracts outside the CArG-box suggest additional roles for this structure
      in the process of DNA binding of these transcription factors. Structural
      characteristics of the CArG-box not only play an important role in DNA-binding
      site recognition of MADS-domain proteins, but also partly explain differences in
      DNA-binding specificity of different members of this transcription factor family
      and their heteromeric complexes. 

PMID- 24275493
TI  - The Ddx5 and Ddx17 RNA helicases are cornerstones in the complex regulatory array
      of steroid hormone-signaling pathways.
AB  - Estrogen and androgen receptors (ER and AR) play key roles in breast and prostate
      cancers, respectively, where they regulate the transcription of large arrays of
      genes. The activities of ER and AR are controlled by large networks of protein
      kinases and transcriptional coregulators, including Ddx5 and its highly related
      paralog Ddx17. The Ddx5 and Ddx17 RNA helicases are also splicing regulators.
      Here, we report that Ddx5 and Ddx17 are master regulators of the estrogen- and
      androgen-signaling pathways by controlling transcription and splicing both
      upstream and downstream of the receptors. First, Ddx5 and Ddx17 are required
      downstream of ER and AR for the transcriptional and splicing regulation of a
      large number of steroid hormone target genes. Second, Ddx5 and Ddx17 act upstream
      of ER and AR by controlling the expression, at the splicing level, of several key
      regulators of ER and AR activities. Of particular interest, we demonstrate that
      Ddx5 and Ddx17 control alternative splicing of the GSK3beta kinase, which impacts
      on both ER and AR protein stability. We also provide a freely available online
      resource which gives information regarding splicing variants of genes involved in
      the estrogen- and androgen-signaling pathways. 

PMID- 24275494
TI  - 1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of
      natural selection in modern humans.
AB  - Searching for Darwinian selection in natural populations has been the focus of a
      multitude of studies over the last decades. Here we present the 1000 Genomes
      Selection Browser 1.0 (http://hsb.upf.edu) as a resource for signatures of recent
      natural selection in modern humans. We have implemented and applied a large
      number of neutrality tests as well as summary statistics informative for the
      action of selection such as Tajima's D, CLR, Fay and Wu's H, Fu and Li's F* and
      D*, XPEHH, DeltaiHH, iHS, F(ST), DeltaDAF and XPCLR among others to low coverage
      sequencing data from the 1000 genomes project (Phase 1; release April 2012). We
      have implemented a publicly available genome-wide browser to communicate the
      results from three different populations of West African, Northern European and
      East Asian ancestry (YRI, CEU, CHB). Information is provided in UCSC-style format
      to facilitate the integration with the rich UCSC browser tracks and an access
      page is provided with instructions and for convenient visualization. We believe
      that this expandable resource will facilitate the interpretation of signals of
      selection on different temporal, geographical and genomic scales.

PMID- 24275495
TI  - miRBase: annotating high confidence microRNAs using deep sequencing data.
AB  - We describe an update of the miRBase database (http://www.mirbase.org/), the
      primary microRNA sequence repository. The latest miRBase release (v20, June 2013)
      contains 24 521 microRNA loci from 206 species, processed to produce 30 424
      mature microRNA products. The rate of deposition of novel microRNAs and the
      number of researchers involved in their discovery continue to increase, driven
      largely by small RNA deep sequencing experiments. In the face of these increases,
      and a range of microRNA annotation methods and criteria, maintaining the quality
      of the microRNA sequence data set is a significant challenge. Here, we describe
      recent developments of the miRBase database to address this issue. In particular,
      we describe the collation and use of deep sequencing data sets to assign levels
      of confidence to miRBase entries. We now provide a high confidence subset of
      miRBase entries, based on the pattern of mapped reads. The high confidence
      microRNA data set is available alongside the complete microRNA collection at
      http://www.mirbase.org/. We also describe embedding microRNA-specific Wikipedia
      pages on the miRBase website to encourage the microRNA community to contribute
      and share textual and functional information. 

PMID- 24275496
TI  - CyanoBase and RhizoBase: databases of manually curated annotations for
      cyanobacterial and rhizobial genomes.
AB  - To understand newly sequenced genomes of closely related species, comprehensively
      curated reference genome databases are becoming increasingly important. We have
      extended CyanoBase (http://genome.microbedb.jp/cyanobase), a genome database for
      cyanobacteria, and newly developed RhizoBase
      (http://genome.microbedb.jp/rhizobase), a genome database for rhizobia, nitrogen
      fixing bacteria associated with leguminous plants. Both databases focus on the
      representation and reusability of reference genome annotations, which are
      continuously updated by manual curation. Domain experts have extracted names,
      products and functions of each gene reported in the literature. To ensure
      effectiveness of this procedure, we developed the TogoAnnotation system offering
      a web-based user interface and a uniform storage of annotations for the curators
      of the CyanoBase and RhizoBase databases. The number of references investigated
      for CyanoBase increased from 2260 in our previous report to 5285, and for
      RhizoBase, we perused 1216 references. The results of these intensive annotations
      are displayed on the GeneView pages of each database. Advanced users can also
      retrieve this information through the representational state transfer-based web
      application programming interface in an automated manner. 

PMID- 24275497
TI  - Differences between cotranscriptional and free riboswitch folding.
AB  - Riboswitches are part of noncoding regions of messenger RNA (mRNA) that act as
      RNA sensors regulating gene expression of the downstream gene. Typically, one out
      of two distinct conformations is formed depending on ligand binding when the
      transcript leaves RNA polymerase (RNAP). Elongation of the RNA chain by RNAP,
      folding and binding all occurs simultaneously and interdependently on the
      seconds' timescale. To investigate the effect of transcript elongation velocity
      on folding for the S-adenosylmethionine (SAM)-I and adenine riboswitches we
      employ two complementary coarse-grained in silico techniques. Native structure
      based molecular dynamics simulations provide a 3D, atomically resolved model of
      folding with homogenous energetics. Energetically more detailed kinetic Monte
      Carlo simulations give access to longer timescale by describing folding on the
      secondary structure level and feature the incorporation of competing aptamer
      conformations and a ligand-binding model. Depending on the extrusion scenarios,
      we observe and quantify different pathways in structure formation with robust
      agreements between the two techniques. In these scenarios, free-folding
      riboswitches exhibit different folding characteristics compared with
      transcription-rate limited folding. The critical transcription rate
      distinguishing these cases is higher than physiologically relevant rates. This
      result suggests that in vivo folding of the analyzed SAM-I and adenine
      riboswitches is transcription-rate limited. 

PMID- 24275498
TI  - Lattice and polarizability mediated spin activity in EuTiO3.
AB  - EuTiO3 is shown to exhibit novel strong spin-charge-lattice coupling deep in the
      paramagnetic phase. Its existence is evidenced by an, until now, unknown response
      of the paramagnetic susceptibility at temperatures exceeding the structural phase
      transition temperature T(S) = 282 K. The 'extra' features in the susceptibility
      follow the rotational soft zone boundary mode temperature dependence above and
      below TS. The theoretical modeling consistently reproduces this behavior and
      provides reasoning for the stabilization of the soft optic mode other than
      quantum fluctuations.

PMID- 24275499
TI  - Systematic review of the Hawthorne effect: new concepts are needed to study
      research participation effects.
AB  - OBJECTIVES: This study aims to (1) elucidate whether the Hawthorne effect exists,
      (2) explore under what conditions, and (3) estimate the size of any such effect.
      STUDY DESIGN AND SETTING: This systematic review summarizes and evaluates the
      strength of available evidence on the Hawthorne effect. An inclusive definition
      of any form of research artifact on behavior using this label, and without
      cointerventions, was adopted. RESULTS: Nineteen purposively designed studies were
      included, providing quantitative data on the size of the effect in eight
      randomized controlled trials, five quasiexperimental studies, and six
      observational evaluations of reporting on one's behavior by answering questions
      or being directly observed and being aware of being studied. Although all but one
      study was undertaken within health sciences, study methods, contexts, and
      findings were highly heterogeneous. Most studies reported some evidence of an
      effect, although significant biases are judged likely because of the complexity
      of the evaluation object. CONCLUSION: Consequences of research participation for
      behaviors being investigated do exist, although little can be securely known
      about the conditions under which they operate, their mechanisms of effects, or
      their magnitudes. New concepts are needed to guide empirical studies.

PMID- 24275500
TI  - A novel research design can aid disinvestment from existing health technologies
      with uncertain effectiveness, cost-effectiveness, and/or safety.
AB  - OBJECTIVES: Disinvestment is critical for ensuring the long-term sustainability
      of health-care services. Key barriers to disinvestment are heterogeneity between
      research and clinical settings, absence of evidence of effectiveness of some
      health technologies, and exposure of patients and organizations to risks and poor
      outcomes. We aimed to develop a feasible research design that can evaluate
      disinvestment in health technologies of uncertain effectiveness or cost
      effectiveness. STUDY DESIGN AND SETTING: This article (1) establishes the need
      for disinvestment methodologies, (2) identifies the ethical concerns and
      feasibility constraints of conventional research designs for this issue, (3)
      describes the planning, implementation, and analytical framework for a novel
      disinvestment-specific study design, and (4) describes potential limitations in
      application of this design. RESULTS: The stepped-wedge, roll-in cluster
      randomized controlled trial can facilitate the disinvestment process, whereas
      generating evidence to determine whether the decision to disinvest was sound in
      the clinical environment. A noninferiority research paradigm may be applied to
      this methodology to demonstrate that the removal of a health technology does not
      adversely affect outcomes. CONCLUSION: This research design can be applied across
      multiple fields and will assist determination of whether specific health
      technologies are clinically effective, cost-effective, and safe.

PMID- 24275501
TI  - Causal inference algorithms can be useful in life course epidemiology.
AB  - OBJECTIVES: Life course epidemiology attempts to unravel causal relationships
      between variables observed over time. Causal relationships can be represented as
      directed acyclic graphs. This article explains the theoretical concepts of the
      search algorithms used for finding such representations, discusses various types
      of such algorithms, and exemplifies their use in the context of obesity and
      insulin resistance. STUDY DESIGN AND SETTING: We investigated possible causal
      relations between gender, birth weight, waist circumference, and blood glucose
      level of 4,081 adult participants of the Prevention of REnal and Vascular ENd
      stage Disease study. The latter two variables were measured at three time points
      at intervals of about 3 years. RESULTS: We present the resulting causal graphs,
      estimate parameters of the corresponding structural equation models, and discuss
      usefulness and limitations of this methodology. CONCLUSION: As an exploratory
      method, causal graphs and the associated theory can help construct possible
      causal models underlying observational data. In this way, the causal search
      algorithms provide a valuable statistical tool for life course epidemiological
      research.

PMID- 24275502
TI  - Pupil responses derived from outer and inner retinal photoreception are normal in
      patients with hereditary optic neuropathy.
AB  - We compared the pupil responses originating from outer versus inner retinal
      photoreception between patients with isolated hereditary optic neuropathy (HON, n
      = 8) and healthy controls (n = 8). Three different testing protocols were used.
      For the first two protocols, a response function of the maximal pupil contraction
      versus stimulus light intensity was generated and the intensity at which half of
      the maximal pupil contraction, the half-max intensity, was determined. For the
      third protocol, the pupil size after light offset, the re-dilation rate and re
      dilation amplitude were calculated to assess the post-light stimulus response.
      Patients with HON had bilateral, symmetric optic atrophy and significant
      reduction of visual acuity and visual field compared to controls. There were no
      significant mean differences in the response curve and pupil response parameters
      that reflect mainly rod, cone or melanopsin activity between patients and
      controls. In patients, there was a significant correlation between the half-max
      intensity of the red light sequence and visual field loss. In conclusion, pupil
      responses derived from outer or inner retinal photoreception in HON patients
      having mild-to moderate visual dysfunction are not quantitatively different from
      age-matched controls. However, an association between the degree of visual field
      loss and the half-max intensity of the cone response suggests that more advanced
      stages of disease may lead to impaired pupil light reflexes. 

PMID- 24275503
TI  - [RECOT and the future of medical journals in the digital age].

PMID- 24275504
TI  - Typhoon Haiyan and beyond.

PMID- 24275505
TI  - Detection of imidacloprid in biological fluids in a case of fatal insecticide
      intoxication.
AB  - Here, we describe a high-performance liquid chromatography/photodiode array
      detector method for the detection of imidacloprid in biological fluids in a case
      of suicide by ingestion of liquor mixed with Admire(r) Flowable insecticide
      (containing 20% imidacloprid). A plastic bottle containing a cloudy liquid
      (concentration of ethanol in the liquid was 150 mg/ml and that of imidacloprid
      was 50 mg/ml) was found near the decedent. The biological fluids collected at
      autopsy were prepared by deproteinization with acetonitrile. Zolpidem was used as
      an internal standard. The concentrations of imidacloprid in femoral blood and
      cerebrospinal fluid were 105 and 58.5 MUg/ml, respectively. Ethanol was also
      detected in the samples, with concentrations of 1.0 mg/ml in femoral blood and
      1.4 mg/ml in cerebrospinal fluid.

PMID- 24275506
TI  - Probing the relation between protein-protein interactions and DNA binding for a
      linker mutant of the bacterial nucleoid protein H-NS.
AB  - We have investigated the relationship between oligomerization in solution and DNA
      binding for the bacterial nucleoid protein H-NS. This was done by comparing
      oligomerization and DNA binding of H-NS with that of a H-NS D68V-D71V linker
      mutant. The double linker mutation D68V-D71V, that makes the linker significantly
      more hydrophobic, leads to a dramatically enhanced and strongly temperature
      dependent H-NS oligomerization in solution, as detected by dynamic light
      scattering. The DNA binding affinity of H-NS D68V-D71V for the hns promoter
      region is lower and has stronger temperature dependence than that of H-NS. DNase
      I footprinting experiments show that at high concentrations, regions protected by
      H-NS D68V-D71V are larger and less defined than for H-NS. In vitro transcription
      assays show that the enhanced protection also leads to enhanced transcriptional
      repression. Whereas the lower affinity of the H-NS D68V-D71V for DNA could be
      caused by competition between oligomerization in solution and oligomerization on
      DNA, the larger size of protected regions clearly confirms the notion that
      cooperative binding of H-NS to DNA is related to protein-protein interactions.
      These results emphasize the relative contributions of protein-protein
      interactions and substrate-dependent oligomerization in the control of gene
      repression operated by H-NS. 

PMID- 24275507
TI  - Secreted major Venus flytrap chitinase enables digestion of Arthropod prey.
AB  - Predation plays a major role in energy and nutrient flow in the biological food
      chain. Plant carnivory has attracted much interest since Darwin's time, but many
      fundamental properties of the carnivorous lifestyle are largely unexplored. In
      particular, the chain of events leading from prey perception to its digestive
      utilization remains to be elucidated. One of the first steps after the capture of
      animal prey, i.e. the enzymatic breakup of the insects' chitin-based shell, is
      reflected by considerable chitinase activity in the secreted digestive fluid in
      the carnivorous plant Venus flytrap. This study addresses the molecular nature,
      function, and regulation of the underlying enzyme, VF chitinase-I. Using mass
      spectrometry based de novo sequencing, VF chitinase-I was identified in the
      secreted fluid. As anticipated for one of the most prominent proteins in the
      flytrap's "green stomach" during prey digestion, transcription of VF chitinase-I
      is restricted to glands and enhanced by secretion-inducing stimuli. In their
      natural habitat, Venus flytrap is exposed to high temperatures. We expressed and
      purified recombinant VF chitinase-I and show that the enzyme exhibits the
      hallmark properties expected from an enzyme active in the hot and acidic
      digestive fluid of Dionaea muscipula. Structural modeling revealed a relative
      compact globular form of VF chitinase-I, which might contribute to its overall
      stability and resistance to proteolysis. These peculiar characteristics could
      well serve industrial purposes, especially because of the ability to hydrolyze
      both soluble and crystalline chitin substrates including the commercially
      important cleavage of alpha-chitin. 

PMID- 24275508
TI  - Structural and biochemical analyses of Microcystis aeruginosa O-acetylserine
      sulfhydrylases reveal a negative feedback regulation of cysteine biosynthesis.
AB  - O-acetylserine sulfhydrylase (OASS) catalyzes the final step of cysteine
      biosynthesis from O-acetylserine (OAS) and inorganic sulfide in plants and
      bacteria. Bioinformatics analyses combined with activity assays enabled us to
      annotate the two putative genes of Microcystis aeruginosa PCC 7806 to CysK1 and
      CysK2, which encode the two 75% sequence-identical OASS paralogs. Moreover, we
      solved the crystal structures of CysK1 at 2.30A and cystine-complexed CysK2 at
      1.91A, revealing a quite similar overall structure that belongs to the family of
      fold-type II PLP-dependent enzymes. Structural comparison indicated a significant
      induced fit upon binding to the cystine, which occupies the binding site for the
      substrate OAS and blocks the product release tunnel. Subsequent enzymatic assays
      further confirmed that cystine is a competitive inhibitor of the substrate OAS.
      Moreover, multiple-sequence alignment revealed that the cystine-binding residues
      are highly conserved in all OASS proteins, suggesting that this auto-inhibition
      of cystine might be a universal mechanism of cysteine biosynthesis pathway. 

PMID- 24275509
TI  - Inflammation, caveolae and CD38-mediated calcium regulation in human airway
      smooth muscle.
AB  - The pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) increases
      expression of CD38 (a membrane-associated bifunctional enzyme regulating cyclic
      ADP ribose), and enhances agonist-induced intracellular Ca(2+) ([Ca(2+)]i)
      responses in human airway smooth muscle (ASM). We previously demonstrated that
      caveolae and their constituent protein caveolin-1 are important for ASM [Ca(2+)]i
      regulation, which is further enhanced by TNFalpha. Whether caveolae and CD38 are
      functionally linked in mediating TNFalpha effects is unknown. In this regard,
      whether the related cavin proteins (cavin-1 and -3) that maintain structure and
      function of caveolae play a role is also not known. In the present study, we
      hypothesized that TNFalpha effects on CD38 expression and function in human ASM
      involve caveolae. Caveolar fractions from isolated human ASM cells expressed CD38
      and its expression was upregulated by exposure to 20ng/ml TNFalpha (48h). ASM
      cells expressed cavin-1 and cavin-3, which were also upregulated by TNFalpha.
      Knockdown of caveolin-1, cavin-1 or cavin-3 (using siRNA) all significantly
      reduced CD38 expression and ADP-ribosyl cyclase activity in the presence or
      absence of TNFalpha. Furthermore, caveolin-1, cavin-1 and cavin-3 siRNAs reduced
      [Ca(2+)]i responses to histamine under control conditions, and blunted the
      enhanced [Ca(2+)]i responses in TNFalpha-exposed cells. These data demonstrate
      that CD38 is expressed within caveolae and its function is linked to the caveolar
      regulatory proteins caveolin-1, cavin-1 and -3. The link between caveolae and
      CD38 is further enhanced during airway inflammation demonstrating the important
      role of caveolae in regulation of [Ca(2+)]i and contractility in the airway. 

PMID- 24275510
TI  - Alpha-crystallin-mediated protection of lens cells against heat and oxidative
      stress-induced cell death.
AB  - In addition to their key role as structural lens proteins, alpha-crystallins also
      appear to confer protection against many eye diseases, including cataract,
      retinitis pigmentosa, and macular degeneration. Exogenous recombinant alpha
      crystallin proteins were examined for their ability to prevent cell death induced
      by heat or oxidative stress in a human lens epithelial cell line (HLE-B3). Wild
      type alphaA- or alphaB-crystallin (WT-alphaA and WT-alphaB) and alphaA- or alphaB
      crystallins, modified by the addition of a cell penetration peptide (CPP)
      designed to enhance the uptake of proteins into cells (gC-alphaB, TAT-alphaB, gC
      alphaA), were produced by recombinant methods. In vitro chaperone-like assays
      were used to assay the ability of alpha-crystallins to protect client proteins
      from chemical or heat induced aggregation. In vivo viability assays were
      performed in HLE-B3 to determine whether pre-treatment with alpha-crystallins
      reduced death after exposure to oxidative or heat stress. Most of the five
      recombinant alpha-crystallin proteins tested conferred some in vitro protection
      from protein aggregation, with the greatest effect seen with WT-alphaB and gC
      alphaB. All alpha-crystallins displayed significant protection to oxidative
      stress induced cell death, while only the alphaB-crystallins reduced cell death
      induced by thermal stress. Our findings indicate that the addition of the gC tag
      enhanced the protective effect of alphaB-crystallin against oxidative but not
      thermally-induced cell death. In conclusion, modifications that increase the
      uptake of alpha-crystallin proteins into cells, without destroying their
      chaperone-like activity and anti-apoptotic functions, create the potential to use
      these proteins therapeutically. 

PMID- 24275511
TI  - Acquiring procedural skills in ICUs: a prospective multicenter study*.
AB  - OBJECTIVES: Providing appropriate training of procedural skills to residents
      while ensuring patient safety through trainee supervision is a difficult and
      constant challenge. We sought to determine how effective and safe procedural
      skill acquisition is in French ICUs and to identify failure and complication risk
      factors. DESIGN: Multicenter prospective observational study. Invasive procedures
      performed by residents were recorded during two consecutive semesters. SETTING:
      Eighty-four residents. SUBJECTS: Eighty-four residents. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: Number of invasive procedures performed, failure
      and complication rates, supervision, and assistance provided. Five thousand six
      hundred seventeen procedures were prospectively studied: 1,007 tracheal
      intubations, 1,272 arterial and 2,586 central venous catheter insertions, 457
      fiberoptic bronchoscopies, and 295 chest tube insertions. During the semesters,
      residents performed a median of 10 intubations, 14 arterial catheter insertions,
      and 26 central venous catheter insertions. Complication rates were low, similar
      to those in the literature: 8.6% desaturation and 7.4% esophageal placement
      during intubation; 0.4% and 2.3% pneumothorax with jugular and subclavian central
      venous catheter insertions, respectively. We identified risk factors for failure
      and complications. Higher rates of failure and complications for intubation were
      associated with residents with no or little previous experience (p < 0.001);
      failure of internal jugular vein catheterization was associated with left-side
      insertion (p = 0.005) and absence of mechanical ventilation (p = 0.007).
      Supervision and assistance were more frequent at the beginning of the semester
      and for intubation and chest tube insertion. Finally, residents had less access
      to fiberoptic bronchoscopy and chest tube insertion. CONCLUSION: Procedural
      skills acquisition by residents in the ICU appears feasible and safe with
      complication rates comparable to what has previously been reported. We identified
      specific procedures and situations associated with higher failure and
      complication rates that could require proactive training. Questions still remain
      regarding minimal numbers of procedures to attain competence and how best to
      provide procedural training.

PMID- 24275512
TI  - Use of intensive care services and associated hospital mortality after
      Massachusetts healthcare reform*.
AB  - OBJECTIVE: To use the natural experiment of health insurance reform in
      Massachusetts to study the impact of increased insurance coverage on ICU
      utilization and mortality. DESIGN: Population-based cohort study. SETTING:
      Massachusetts and four states (New York, Washington, Nebraska, and North
      Carolina) that did not enact reform. PATIENTS: All nonpregnant nonelderly adults
      (age 18-64 yr) admitted to nonfederal acute care hospitals in one of the five
      states of interest were eligible, excluding patients who were not residents of a
      respective state at the time of admission. MEASUREMENTS: We used a difference-in
      differences approach to compare trends in ICU admissions and outcomes of in
      hospital mortality and discharge destination for ICU patients. MAIN RESULT:
      Healthcare reform in Massachusetts was associated with a decrease in ICU patients
      without insurance from 9.3% to 5.1%. There were no significant changes in
      adjusted ICU admission rates, mortality, or discharge destination. In a
      sensitivity analysis excluding a state that enacted Medicaid reform prior to the
      study period, our difference-in-differences analysis demonstrated a significant
      increase in mortality of 0.38% per year (95% CI, 0.12-0.64%) in Massachusetts,
      attributable to a greater per-year decrease in mortality postreform in comparison
      states (-0.37%; 95% CI, -0.52% to -0.21%) compared with Massachusetts (0.01%; 95%
      CI, -0.20% to 0.11%). CONCLUSION: Massachusetts healthcare reform increased the
      number of ICU patients with insurance but was not associated with significant
      changes in ICU use or discharge destination among ICU patients. Reform was also
      not associated with changed in-hospital mortality for ICU patients; however, this
      association was dependent on the comparison states chosen in the analysis.

PMID- 24275513
TI  - The association between renal replacement therapy modality and long-term outcomes
      among critically ill adults with acute kidney injury: a retrospective cohort
      study*.
AB  - OBJECTIVE: Among critically ill patients with acute kidney injury, the impact of
      renal replacement therapy modality on long-term kidney function is unknown.
      Compared with conventional intermittent hemodialysis, continuous renal
      replacement therapy may promote kidney recovery by conferring greater hemodynamic
      stability; yet continuous renal replacement therapy may not enhance patient
      survival and is resource intense. Our objective was to determine whether
      continuous renal replacement therapy was associated with a lower risk of chronic
      dialysis as compared with intermittent hemodialysis, among survivors of acute
      kidney injury. DESIGN: Retrospective cohort study. SETTING: Linked population
      wide administrative databases in Ontario, Canada. PATIENTS: Critically ill adults
      who initiated dialysis for acute kidney injury between July 1996 and December
      2009. In the primary analysis, we considered those who survived to at least 90
      days after renal replacement therapy initiation. INTERVENTIONS: Initial receipt
      of continuous renal replacement therapy versus intermittent hemodialysis.
      MEASUREMENTS AND MAIN RESULTS: Continuous renal replacement therapy recipients
      were matched 1:1 to intermittent hemodialysis recipients based on a history of
      chronic kidney disease, receipt of mechanical ventilation, and a propensity score
      for the likelihood of receiving continuous renal replacement therapy. Cox
      proportional hazards were used to evaluate the relationship between initial renal
      replacement therapy modality and the primary outcome of chronic dialysis, defined
      as the need for dialysis for a consecutive period of 90 days. We identified 2,315
      continuous renal replacement therapy recipients of whom 2,004 (87%) were
      successfully matched to 2,004 intermittent hemodialysis recipients. Participants
      were followed over a median duration of 3 years. The risk of chronic dialysis was
      significantly lower among patients who initially received continuous renal
      replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI,
      0.65-0.87). This relation was more prominent among those with preexisting chronic
      kidney disease (p value for interaction term = 0.065) and heart failure (p value
      for interaction term = 0.035). CONCLUSIONS: Compared with intermittent
      hemodialysis, initiation of continuous renal replacement therapy in critically
      ill adults with acute kidney injury is associated with a lower likelihood of
      chronic dialysis.

PMID- 24275514
TI  - Catatonia in the ICU: an important and underdiagnosed cause of altered mental
      status. a case series and review of the literature*.
AB  - OBJECTIVE: Catatonia is a neuropsychiatric syndrome with motor and behavioral
      symptoms occurring in patients with or without a history of psychiatric illness.
      Although it is associated with significant morbidity and mortality, the
      prevalence of catatonia in the ICU setting is unknown. The diagnosis and
      management of catatonia in the critically ill patient raises unique challenges.
      Furthermore, the diagnosis and management are not included in most critical care
      curricula. The objective of this retrospective study is to increase the awareness
      of this clinically important condition among critical care providers. DESIGN:
      Retrospective case series study. SETTING: Multiple critical care units at a
      university-affiliated tertiary care hospital. PATIENTS: Five critically ill
      patients with catatonia, aged 17 to 78. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: All notes, laboratory data, imaging results, other diagnostic
      studies, therapeutic interventions, and responses to treatment were reviewed for
      five critically ill patients with catatonia. No unifying cause of catatonia or
      predisposing conditions were identified for these patients. Currently available
      diagnostic criteria for catatonia were found to be nonspecific in the ICU
      setting. New diagnostic criteria for catatonia specific to the critically ill
      patient are proposed. CONCLUSIONS: Catatonia can occur in a wide variety of
      critical care settings, with or without precedent psychiatric illness, and it may
      be exacerbated or induced by common intensive care practices. Psychomotor
      findings are imperative in examination of critically ill patients with altered
      mental status in order to diagnose catatonia.

PMID- 24275515
TI  - [Torpedo maculopathy: anatomic and functional description].

PMID- 24275516
TI  - [Pseudophakic retinal detachment: how to manage?].
AB  - INTRODUCTION: Retinal detachment, a common complication of cataract surgery,
      requires urgent surgical treatment. The external approach combining retinopexy
      with scleral buckling remains the gold standard in the surgical management of
      pseudophakic retinal detachment (RD) without marked proliferative
      vitreoretinopathy (PVR), although intraocular surgery is currently preferred by
      most of the authors. The purpose of this study is to compare the anatomical and
      functional results obtained with both techniques. PATIENTS AND METHODS: This
      study compares the results of two techniques for treating pseudophakic retinal
      detachment: external surgery (group I), and vitrectomy with internal tamponade
      (group II). Ab-externo surgery was performed in 24 patients (24 eyes), while 22
      patients (22 eyes) underwent primary vitrectomy. In order to make both groups
      comparable, we excluded recurrences of RD, vitreous hemorrhage and other media
      opacities, giant tears and initial grade C PVR. Minimum follow-up was 12 months.
      Postoperative variables analyzed and compared were the rate of initial and final
      anatomical success, final visual acuity, and causes of failure of the initial
      surgery. RESULTS: The retina was reattached with a single operation in 21 eyes in
      group I (87.5%) and 19 eyes in group II (86.4%) (P=0.91). The causes of
      anatomical failure in both groups were proliferative vitreoretinopathy (4 cases)
      and secondary tears or tears not seen on initial examination (2 cases). For
      patients in group I, secondary surgery consisted of total vitrectomy with
      encircling buckle. Patients in group II underwent an additional vitrectomy
      (peeling of vitreoretinal proliferation, and silicone oil tamponade as
      necessary). After a mean follow-up of 12 months, the final examination noted a
      reattached retina in 23 eyes in group I (95.84%) and 21 eyes in group II (95.45%)
      (P=0.95). The final visual results were identical at comparable follow-up
      periods. Indeed, the final visual acuity was similar in the two groups with
      nearly 40% of patients having recovered visual acuity between 1/10 and 5/10
      (P=0.98). CONCLUSION: With regard to surgical treatment of pseudophakic retinal
      detachment, vitrectomy with internal tamponade provides anatomical and functional
      results comparable to those obtained with external surgery.

PMID- 24275517
TI  - [Cosmetic eyelid surgery].
AB  - Cosmetic eyelid surgery is becoming increasingly popular. It can rejuvenate the
      patient's appearance with relatively minor side effects. Its risk/benefit ratio
      is one of the best in facial cosmetic surgery. However, the patient does not
      always accurately assess the aesthetic appearance of his or her eyelids. This
      underscores the importance of clinical examination in order to determine the
      patient's wishes, and then make an accurate diagnosis and potential surgical
      plan. We currently oppose, in general, surgical techniques involving tissue
      removal (skin-muscle and/or fat) in favor of those involving tissue repositioning
      and grafting (autologous fat pearl transposition, obtained by liposuction, and
      lipostructure). Furthermore, the place of adjuvant therapies to blepharoplasty is
      steadily increasing. They mainly include surface treatments (peels and lasers),
      dermal fillers and anti-wrinkle botulinum toxin injections. They are also
      increasingly used in isolation in novel ways. In all cases, a perfect knowledge
      of anatomy and relevant skills and experience remain necessary. 

PMID- 24275518
TI  - Impact of the transition from screen-film to digital screening mammography on
      interval cancer characteristics and treatment - a population based study from the
      Netherlands.
AB  - INTRODUCTION: In most breast screening programmes screen-film mammography (SFM)
      has been replaced by full-field digital mammography (FFDM). We compared interval
      cancer characteristics at SFM and FFDM screening mammography. PATIENTS AND
      METHODS: We included all 297 screen-detected and 104 interval cancers in 60,770
      SFM examinations and 427 screen-detected and 124 interval cancers in 63,182 FFDM
      examinations, in women screened in the period 2008-2010. Breast imaging reports,
      biopsy results and surgical reports of all cancers were collected. Two
      radiologists reviewed prior and diagnostic mammograms of all interval cancers.
      They determined breast density, described mammographic abnormalities and
      classified interval cancers as missed, showing a minimal sign abnormality or true
      negative. RESULTS: The referral rate and cancer detection at SFM were 1.5% and
      4.90/00 respectively, compared to 3.0% (p<0.001) and 6.60/00 (p<0.001) at FFDM.
      Screening sensitivity was 74.1% at SFM (297/401, 95% confidence interval
      (CI)=69.8-78.4%) and 77.5% at FFDM (427/551, 95% CI=74.0-81.0%). Significantly
      more interval cancers were true negative at prior FFDM than at prior SFM
      screening mammography (65.3% (81/124) versus 47.1% (49/104), p=0.02). For
      interval cancers following SFM or FFDM screening mammography, no significant
      differences were observed in breast density or mammographic abnormalities at the
      prior screen, tumour size, lymph node status, receptor status, Nottingham tumour
      grade or surgical treatment (mastectomy versus breast conserving therapy).
      CONCLUSION: FFDM resulted in a significantly higher cancer detection rate, but
      sensitivity was similar for SFM and FFDM. Interval cancers are more likely to be
      true negative at prior FFDM than at prior SFM screening mammography, whereas
      their tumour characteristics and type of surgical treatment are comparable.

PMID- 24275519
TI  - The application of ultra-weak photon emission in dermatology.
AB  - Ultra-weak photo emission (UPE) is a phenomenon closely associated with life and
      provides us a rare window to look into oxidative reactions in life directly
      without the aid of other agents. Dozens of independent studies have investigated
      UPE in skin in the last 2 decades. Skin serves as a convenient target for the
      application of UPE. As the outmost layer of our body, skin is also subjected to
      the influences from environmental factors such as ultraviolet light. Therefore
      UPE measurement can help us better understand the interaction between skin and
      the outside world. A variety of dermatological interventions may benefit from UPE
      studies. In particular, those treatments aiming to manage the oxidative status of
      the skin can be monitored directly by UPE measurements. In recent years, UPE has
      already been used as a valuable in vivo tool to assist the selection of better
      skin care ingredients and products. The knowledge gained by UPE studies of skin
      may also help generate new insights and new targets for future treatments. This
      review emphasizes in vivo and clinical measurement of UPE in skin. The
      applications of UPE in skin research related to antioxidants and sunscreens are
      discussed.

PMID- 24275520
TI  - Sensitivity testing of the Seizure Severity Questionnaire (SSQ).
AB  - The sensitivity of the Seizure Severity Questionnaire (SSQ) was evaluated using
      pooled data from open-label extensions of two clinical trials in patients with
      partial-onset seizures. The SSQ includes questions relating to frequency and
      helpfulness of warning signs as well as frequency, severity, and bothersomeness
      of ictal and postictal effects. Differences between mean change from baseline for
      each SSQ item for responders and nonresponders were described and compared
      between patients solely with complex partial seizures (CPSs: responders, n=166;
      nonresponders, n=127) and those solely with secondarily generalized partial
      seizures (SGPSs: responders, n=26; nonresponders, n=24) at baseline. Seizure
      Severity Questionnaire total score and individual SSQ items related to ictal
      movement, consciousness, bothersomeness of postictal effects, and frequency of
      postictal emotional effects showed differentiation between seizure type
      responders. These data provide further validation of the SSQ by demonstrating its
      sensitivity in describing treatment effects. 

PMID- 24275521
TI  - Phylogenetic analysis reveals conservation and diversification of micro RNA166
      genes among diverse plant species.
AB  - Similar to the majority of the microRNAs, mature miR166s are derived from
      multiple members of MIR166 genes (precursors) and regulate various aspects of
      plant development by negatively regulating their target genes (Class III HD-ZIP).
      The evolutionary conservation or functional diversification of miRNA166 family
      members remains elusive. Here, we show the phylogenetic relationships among
      MIR166 precursor and mature sequences from three diverse model plant species.
      Despite strong conservation, some mature miR166 sequences, such as ppt-miR166m,
      have undergone sequence variation. Critical sequence variation in ppt-miR166m has
      led to functional diversification, as it targets non-HD-ZIPIII gene transcript
      (s). MIR166 precursor sequences have diverged in a lineage specific manner, and
      both precursors and mature osa-miR166i/j are highly conserved. Interestingly,
      polycistronic MIR166s were present in Physcomitrella and Oryza but not in
      Arabidopsis. The nature of cis-regulatory motifs on the upstream promoter
      sequences of MIR166 genes indicates their possible contribution to the functional
      variation observed among miR166 species. 

PMID- 24275522
TI  - Autism's cancer connection: the anti-proliferation hypothesis and why it may
      matter.
AB  - Autism remains an idiopathic disorder in 90% of cases. Recent prevalence,
      heritability, and genetic studies are suggestive that epigenetic and, therefore,
      environmental factors are important in autism pathogenesis. Among the
      environmental factors, only some uncommon viral infections and certain drugs have
      been conclusively linked to autism causation. Thalidomide, valproate, terbutaline
      and, most recently, antidepressants are the main drugs reported to elevate autism
      risk. This article discusses a phenomenal relationship between the drugs reported
      to elevate autism risk and the antiproliferative effects of the same drugs and/or
      analogs of the drugs in cancer cells. Cancer treatment has entered a new era
      epigenetic therapy. In cancer cell lines, thalidomide is antiangiogenic and
      antiproliferative via suppression of tumor necrosis factor-alpha (TNF-alpha) and
      downstream effects on the nuclear factor (NFkappaB) cascade. Valproate shares
      similar mechanisms with thalidomide, but is best known in cancer therapy for its
      epigenetic effects as a histone deacetylase inhibitor. Terbutaline, a beta
      adrenergic agonist, acts via adenylyl cyclase and cAMP-PKA signal transduction.
      Current cancer therapy aims to exploit this epigenetic pathway by developing site
      selective cAMP analogs. Last, it has long been noted in preclinical studies that
      some antidepressants are antiproliferative in cancer cells but the mechanisms
      remain unclear. Based on a systematic review of these drugs, it is hypothesized
      that all central nervous system-acting drugs, which show antiproliferative
      effects in cancer cell lines, share the potential to elevate autism risk when
      administered prenatally. It is further posited that, in autism, the drugs act as
      "triggers" that disturb the pro-proliferative fetal milieu using the same, mainly
      epigenetic, mechanisms that they demonstrate in rapidly proliferating cancer
      cells. In addition to their direct antiproliferative effects, evidence is
      suggestive that the drugs may lock in the pro-inflammatory bias of the prenatal
      immune system by preventing normal perinatal dendritic cell maturation. This
      unifying hypothesis for how structurally different drugs elevate autism risk
      could help focus research on other drugs, or other xenobiotics, that may elevate
      autism risk. For example, there is evidence that an old class of drugs, the
      phenothiazines, is antiproliferative in cancer cell lines via inhibition of
      calmodulin and/or histaminic pathways. Promethazine, one of the first
      heterocyclic phenothiazines synthesized, is commonly prescribed during pregnancy;
      however, its role in elevating the risk of autism has not been investigated.
      Based on the anti-proliferation hypothesis, more studies of promethazine and
      other similar drugs are suggested to evaluate their potential to elevate autism
      risk following prenatal exposures. 

PMID- 24275524
TI  - Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin
      microspheres for the treatment of intrinsic urethral sphincter deficiency.
AB  - In this study we developed a tissue engineered bulking agent that consisted of
      adipose-derived stem cells (ADSCs) and silk fibroin microspheres to treat stress
      urinary incontinence caused by severe intrinsic sphincter deficiency (ISD). ISD
      models were established by completely transection of the bilateral pudendal nerve
      (PNT) and confirmed by the decreased leak-point pressure (LPP) and increased
      lumen area of urethra. Injection of silk fibroin microspheres could recover LPP
      and lumen area at 4 weeks but its efficacy disappears at 8, 12 weeks. Moreover,
      it was exciting to find that tissue engineered bulking agent brought long-term
      efficacy (at 4, 8, 12 weeks post-injection) on the recovery of LPP and lumen
      area. Concomitantly with the function, tissue engineered bulking agent treated
      group also improved the urethral sphincter structure as exhibited by better
      tissue regeneration. The findings showed that silk fibroin microspheres alone
      could work effectively in short-term, while tissue engineered bulking agent that
      combined silk fibroin microspheres with ADSCs exhibited promising long-term
      efficacy. This study developed a new strategy of tissue engineered bulking agent
      for future ISD therapy. 

PMID- 24275523
TI  - A cylindrical specimen holder for electron cryo-tomography.
AB  - The use of slab-like flat specimens for electron cryo-tomography restricts the
      range of viewing angles that can be used. This leads to the "missing wedge"
      problem, which causes artefacts and anisotropic resolution in reconstructed
      tomograms. Cylindrical specimens provide a way to eliminate the problem, since
      they allow imaging from a full range of viewing angles around the tilt axis. Such
      specimens have been used before for tomography of radiation-insensitive samples
      at room temperature, but never for frozen-hydrated specimens. Here, we
      demonstrate the use of thin-walled carbon tubes as specimen holders, allowing the
      preparation of cylindrical frozen-hydrated samples of ribosomes, liposomes and
      whole bacterial cells. Images acquired from these cylinders have equal quality at
      all viewing angles, and the accessible tilt range is restricted only by the
      physical limits of the microscope. Tomographic reconstructions of these specimens
      demonstrate that the effects of the missing wedge are substantially reduced, and
      could be completely eliminated if a full tilt range was used. The overall quality
      of these tomograms is still lower than that obtained by existing methods, but
      improvements are likely in future. 

PMID- 24275525
TI  - Origins of the high temperature increase of the thermal conductivity of
      transition metal carbides from atomistic simulations.
AB  - To understand the unexpected increase of the thermal conductivity of transition
      metal carbides at high temperatures, we calculate, with atomistic simulations,
      the thermal conductivity of zirconium carbide (ZrC). To account for the common
      substoichiometry of this material, various numbers of carbon vacancies are
      considered. The vibrational part of the conductivity is calculated by empirical
      potential molecular dynamics while the electronic part is calculated from density
      functional theory electronic structure with the Kubo-Greenwood formula on
      selected atomic configurations generated by the same empirical potential. We find
      that the vibrational part of the conductivity is negligible at temperatures
      higher than 1500 K. The increase of thermal conductivity with temperature is
      quantitatively reproduced in the calculations. It appears for all compositions
      and proves to rely entirely on its electronic component. Three phenomena are
      found responsible for the rise of the thermal conductivity with temperature: the
      semi-metallic shape of the electronic density of states, the additional
      electrical resistivity induced by carbon vacancies and the rise of the density of
      states with either temperature or the concentration of vacancies. 

PMID- 24275527
TI  - Nuclear trafficking of Pten after brain injury leads to neuron survival not
      death.
AB  - There is controversy whether accumulation of the tumor suppressor PTEN protein in
      the cell nucleus under stress conditions such as trauma and stroke causes cell
      death. A number of in vitro studies have reported enhanced apoptosis in neurons
      possessing nuclear PTEN, with the interpretation that its nuclear phosphatase
      activity leads to reduction of the survival protein phospho-Akt. However, there
      have been no in vivo studies to show that nuclear PTEN in neurons under stress is
      detrimental. Using a mouse model of injury, we demonstrate here that brain trauma
      altered the nucleo-cytoplasmic distribution of Pten, resulting in increased
      nuclear Pten but only in surviving neurons near the lesion. This event was driven
      by Ndfip1, an adaptor and activator of protein ubiquitination by Nedd4 E3
      ligases. Neurons next to the lesion with nuclear PTEN were invariably negative
      for TUNEL, a marker for cell death. These neurons also showed increased Ndfip1
      which we previously showed to be associated with neuron survival. Biochemical
      assays revealed that overall levels of Pten in the affected cortex were unchanged
      after trauma, suggesting that Pten abundance globally had not increased but
      rather Pten subcellular location in affected neurons had changed. Following
      experimental injury, the number of neurons with nuclear Pten was reduced in
      heterozygous mice (Ndfip1(+/-)) although lesion volumes were increased. We
      conclude that nuclear trafficking of Pten following injury leads to neuron
      survival not death. 

PMID- 24275528
TI  - Modeling cell-death patterning during biofilm formation.
AB  - Self-organization by bacterial cells often leads to the formation of a highly
      complex spatially-structured biofilm. In such a bacterial biofilm, cells adhere
      to each other and are embedded in a self-produced extracellular matrix (ECM).
      Bacillus substilis bacteria utilize localized cell-death patterns which focuses
      mechanical forces to form wrinkled sheet-like structures in three dimensions. A
      most intriguing feature underlying this biofilm formation is that vertical
      buckling and ridge location is biased to occur in region of high cell-death. Here
      we present a spatially extended model to investigate the role of the bacterial
      secreted ECM during the biofilm formation and the self-organization of cell
      death. Using this reaction-diffusion model we show that the interaction between
      the cell's motion and the ECM concentration gives rise to a self-trapping
      instability, leading to variety of cell-death patterns. The resultant spot
      patterns generated by our model are shown to be in semi-quantitative agreement
      with recent experimental observation. 

PMID- 24275526
TI  - Glycogen synthase kinase 3 beta regulates glial glutamate transporter protein
      expression in the spinal dorsal horn in rats with neuropathic pain.
AB  - Dysfunctional glial glutamate transporters and over production of pro
      inflammatory cytokines (including interleukin-1beta, IL-1beta) are two prominent
      mechanisms by which glial cells enhance neuronal activities in the spinal dorsal
      horn in neuropathic pain conditions. Endogenous molecules regulating production
      of IL-1beta and glial glutamate functions remain poorly understood. In this
      study, we revealed a dynamic alteration of GSK3beta activities and its role in
      regulating glial glutamate transporter 1 (GLT-1) protein expression in the spinal
      dorsal horn and nociceptive behaviors following the nerve injury. Specifically,
      GSK3beta was expressed in both neurons and astrocytes in the spinal dorsal horn.
      GSK3beta activities were suppressed on day 3 but increased on day 10 following
      the nerve injury. In parallel, protein expression of GLT-1 in the spinal dorsal
      horn was enhanced on day 3 but reduced on day 10. In contrast to these time
      dependent changes, the activation of astrocytes and over-production of IL-1beta
      were found on both day 3 and day 10. Meanwhile, thermal hyperalgesia was observed
      from day 2 through day 10 and mechanical allodynia from day 4 through day 10. Pre
      emptive pharmacological inhibition of GSK3beta activities significantly
      ameliorated thermal hyperalgesia and mechanical allodynia at the late stage but
      did not have effects at the early stage. These were accompanied with the
      suppression of GSK3beta activities, prevention of decreased GLT-1 protein
      expression, inhibition of astrocytic activation, and reduction of IL-1beta in the
      spinal dorsal horn on day 10. These data indicate that the increased GSK3beta
      activity in the spinal dorsal horn is attributable to the downregulation of GLT-1
      protein expression in neuropathic rats at the late stage. Further, we also
      demonstrated that the nerve-injury-induced thermal hyperalgesia on day 10 was
      transiently suppressed by pharmacological inhibition of GSK3beta. Our study
      suggests that GSK3beta may be a potential target for the development of
      analgesics for chronic neuropathic pain. 

PMID- 24275529
TI  - Stability and cell uptake of calcium carbonate templated insulin microparticles.
AB  - Therapeutic proteins are an integral part of today's pharmaceutical practice, but
      they still present challenges from the drug delivery point of view. In this work,
      a new approach is studied based on hard templating for fabrication of
      microparticles composed of pure insulin, which may enable effective delivery, for
      instance pulmonary delivery. The approach is both simple and versatile: the
      protein particles are prepared by selective precipitation into porous CaCO3
      microtemplates, followed by full decomposition of the template at the isoelectric
      point of the protein (pH 5.2). Control over the main material parameters
      (mechanical properties, porosity, morphology and stability at physiological
      conditions) are critical for the envisioned application in drug delivery. It is
      demonstrated that these critical parameters can be significantly tuned by a
      slight final pH variation around the isoelectric point (pH range 4-6) and by the
      denaturation degree of insulin. Electrostatic interactions and inter-protein
      crosslinking in the protein particles as well as their internal structure are
      considered, to explain the variation in the particle properties. The particle
      property parameters are explored using atomic force microscopy, optical
      microscopy and circular dichroism spectra. Finally, phagocytic clearance of the
      protein particles in vitro was studied to explore possible enhancements in
      particle fabrication to improve the efficiency of insulin delivery by inhalation.

PMID- 24275530
TI  - Mercury accumulation in sea lamprey (Petromyzon marinus) from Lake Huron.
AB  - We determined whole-fish total mercury (Hg) concentrations of 40 male and 40
      female adult sea lampreys (Petromyzon marinus) captured in the Cheboygan River, a
      tributary to Lake Huron, during May 2011. In addition, bioenergetics modeling was
      used to explore the effects of sex-related differences in activity and resting
      (standard) metabolic rate (SMR) on mercury accumulation. The grand mean for Hg
      concentrations was 519 ng/g (standard error of the mean=46 ng/g). On average,
      males were 16% higher in Hg concentration than females. Bioenergetics modeling
      results indicated that 14% higher activity and SMR in males would account for
      this observed sex difference in Hg concentrations. We concluded that the higher
      Hg concentration in males was most likely due to higher rate of energy
      expenditure in males, stemming from greater activity and SMR. Our findings have
      implications for estimating the effects of sea lamprey populations on mercury
      cycling within ecosystems, as well as for the proposed opening of sea lamprey
      fisheries. Eventually, our results may prove useful in improving control of sea
      lamprey, a pest responsible for substantial damage to fisheries in lakes where it
      is not native.

PMID- 24275531
TI  - Sonographic features of a juvenile polyp: a case report and literature review.
AB  - Juvenile polyps are a rare form of gastrointestinal polyps and are generally
      diagnosed by colonoscopy or barium enema. In this article, we describe the case
      of a 3-year-old girl with a large juvenile polyp that was diagnosed by abdominal
      ultrasound. Ultrasound examination is necessary for children who pass dark red
      bloody stools either with or without abdominal pain. In addition, mechanical
      bowel preparation before ultrasonic testing is helpful to enable the detection of
      intraluminal lesions. 

PMID- 24275532
TI  - Does the concept of safety culture help or hinder systems thinking in safety?
AB  - The concept of safety culture has become established in safety management
      applications in all major safety-critical domains. The idea that safety culture
      somehow represents a "systemic view" on safety is seldom explicitly spoken out,
      but nevertheless seem to linger behind many safety culture discourses. However,
      in this paper we argue that the "new" contribution to safety management from
      safety culture never really became integrated with classical engineering
      principles and concepts. This integration would have been necessary for the
      development of a more genuine systems-oriented view on safety; e.g. a conception
      of safety in which human, technological, organisational and cultural factors are
      understood as mutually interacting elements. Without of this integration,
      researchers and the users of the various tools and methods associated with safety
      culture have sometimes fostered a belief that "safety culture" in fact represents
      such a systemic view about safety. This belief is, however, not backed up by
      theoretical or empirical evidence. It is true that safety culture, at least in
      some sense, represents a holistic term-a totality of factors that include human,
      organisational and technological aspects. However, the departure for such safety
      culture models is still human and organisational factors rather than technology
      (or safety) itself. The aim of this paper is to critically review the various
      uses of the concept of safety culture as representing a systemic view on safety.
      The article will take a look at the concepts of culture and safety culture based
      on previous studies, and outlines in more detail the theoretical challenges in
      safety culture as a systems concept. The paper also presents recommendations on
      how to make safety culture more systemic. 

PMID- 24275533
TI  - Epidemiological and nonclinical studies investigating effects of iron in
      carcinogenesis--a critical review.
AB  - The efficacy and tolerability of intravenous (i.v.) iron in managing cancer
      related anemia and iron deficiency has been clinically evaluated and reviewed
      recently. However, long-term data in cancer patients are not available; yet, long
      term i.v. iron treatment in hemodialysis patients is not associated with
      increased cancer risk. This review summarizes epidemiological and nonclinical
      data on the role of iron in carcinogenesis. In humans, epidemiological data
      suggest correlations between certain cancers and increased iron exposure or iron
      overload. Nonclinical models that investigated whether iron can enhance
      carcinogenesis provide only limited evidence relevant for cancer patients since
      they were typically based on high iron doses as well as injection routes and iron
      formulations which are not used in the clinical setting. Nevertheless, in the
      absence of long-term outcome data from prospectively defined trials in i.v. iron
      treated cancer patients, iron supplementation should be limited to periods of
      concomitant anti-tumor treatment.

PMID- 24275534
TI  - Ultrasound mediation for one-pot multi-component synthesis of amidoalkyl
      naphthols using new magnetic nanoparticles modified by ionic liquids.
AB  - The ionic liquid 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium acetate was
      immobilized on the Fe3O4 nanoparticles (MNPs-IL-OAc) and used as an efficient new
      heterogeneous nanocatalyst for the one-pot multi-component synthesis of 1
      amidoalkyl-2-naphthols under ultrasound irradiation. The advantages of present
      combined method are the use of a low scale catalyst, easier work-up procedure,
      waste-free, green and efficient synthetic entry to excellent yield of products in
      a high reusability and a short reaction time. 

PMID- 24275535
TI  - DNA probe based colorimetric method for detection of rifampicin resistance of
      Mycobacterium tuberculosis.
AB  - Rifampicin resistance of Mycobacterium tuberculosis is due to the occurrence of
      point mutations of the rpoB gene and the site of mutations vary geographically.
      Commercialized molecular based methods are not able to comprehensively detect
      rifampicin resistance as they target a limited number of gene mutations which are
      thought to be common. The aim of the study was to establish a low cost DNA probe
      based colorimetric method that can be customized for detection of rifampicin
      resistance of M. tuberculosis. Thus, enzyme-linked oligosorbent assay (ELOSA) was
      developed for the detection of polymerase chain reaction (PCR) amplified
      fragments of rpoB gene of M. tuberculosis DNA on microtiter plates. Forty two M.
      tuberculosis isolates (rifampicin resistant and susceptible isolates identified
      by agar proportion method) were used for developing and validating the assay. The
      point mutations of resistant isolates had been previously determined by DNA
      sequencing. Two fragments of rpoB gene were labeled with digoxigenin by PCR. The
      amplified products were hybridized with selected allele specific probes for three
      mutations and its wild types (six probes) which were captured onto streptavidin
      coated microtiter plates and detected by color development. Both sensitivity and
      specificity of all probes were >=96% and there was excellent discrimination (area
      under the curve (AUC)>0.9) between rifampicin susceptible cases and resistant
      cases. The probe-based colorimetric assay (PCR-ELOSA) developed in this study
      showed good agreement with reference mutations that were confirmed by DNA
      sequencing. In conclusion, PCR-ELOSA is a reliable and economical assay that can
      be customized for detection of rifampicin resistance. 

PMID- 24275536
TI  - Computer-aided multiview tumor detection for automated whole breast ultrasound.
AB  - Automated whole breast ultrasound (ABUS) has become a popular screening tool in
      recent years. To reduce the review time and misdetection from ABUS images by
      physicians, a computer-aided detection (CADe) system for ABUS images based on a
      multiview method is proposed in this study. A total of 58 pathology-proven
      lesions from 41 patients were used to evaluate the performance of the system. In
      the proposed CADe system, the fuzzy c-mean clustering method was applied to
      detect tumor candidates from these ABUS images. Subsequently, the tumor
      likelihoods of these candidates could be estimated by a logistic linear
      regression model based on the intensity, morphology, location, and size features
      in the transverse, longitudinal, and coronal views. Finally, the multiview tumor
      likelihoods of the tumor candidates could be obtained from the estimated tumor
      likelihoods of the three views, and the tumor candidates with high multiview
      tumor likelihoods were regarded as the detected tumors in the proposed system.
      The sensitivities of the multiview tumor detection for selecting 5, 10, 20, and
      30 tumor candidates with the largest multiview tumor likelihoods were 79.31%,
      86.21%, 96.55%, and 98.28%, respectively. 

PMID- 24275537
TI  - The effect of dead elements on the accuracy of Doppler ultrasound measurements.
AB  - The objective of this study is to investigate the effect of multiple dead
      elements in an ultrasound probe on the accuracy of Doppler ultrasound
      measurements. For this work, we used a specially designed ultrasound imaging
      system, the Ultrasonix Sonix RP, that provides the user with the ability to
      disable selected elements in the probe. Using fully functional convex, linear,
      and phased array probes, we established a performance baseline by measuring the
      parameters of a laminar parabolic flow profile. These same parameters were then
      measured using probes with 1 to 10 disabled elements. The acquired velocity
      spectra from the functional probes and the probes with disabled elements were
      then analyzed to determine the overall Doppler power, maximum flow velocity, and
      average flow velocity. Color Flow Doppler images were also evaluated in a similar
      manner. The analysis of the Doppler spectra indicates that the overall Doppler
      power as well as the detected maximum and average velocities decrease with the
      increasing number of disabled elements. With multiple disabled elements,
      decreases in the detected maximum and average velocities greater than 20% were
      recorded. Similar results were also observed with Color Flow Doppler
      measurements. Our results confirmed that the degradation of the ultrasound probe
      through the loss of viable elements will negatively affect the quality of the
      Doppler-derived diagnostic information. We conclude that the results of Doppler
      measurements cannot be considered accurate or reliable if there are four or more
      contiguous dead elements in any given probe. 

PMID- 24275538
TI  - Refraction correction in 3D transcranial ultrasound imaging.
AB  - We present the first correction of refraction in three-dimensional (3D)
      ultrasound imaging using an iterative approach that traces propagation paths
      through a two-layer planar tissue model, applying Snell's law in 3D. This
      approach is applied to real-time 3D transcranial ultrasound imaging by
      precomputing delays offline for several skull thicknesses, allowing the user to
      switch between three sets of delays for phased array imaging at the push of a
      button. Simulations indicate that refraction correction may be expected to
      increase sensitivity, reduce beam steering errors, and partially restore lost
      spatial resolution, with the greatest improvements occurring at the largest
      steering angles. Distorted images of cylindrical lesions were created by imaging
      through an acrylic plate in a tissue-mimicking phantom. As a result of correcting
      for refraction, lesions were restored to 93.6% of their original diameter in the
      lateral direction and 98.1% of their original shape along the long axis of the
      cylinders. In imaging two healthy volunteers, the mean brightness increased by
      8.3% and showed no spatial dependency. 

PMID- 24275539
TI  - Two-dimensional simulations of displacement accumulation incorporating shear
      strain.
AB  - Using ultrasound images to track large tissue deformations usually requires
      breaking up the deformation into steps and then summing the resulting
      displacement estimates. The accumulated displacement estimation error therefore
      depends not only on the error in each step but also on the statistical
      relationships between estimation steps. These relationships have not been
      thoroughly studied. Building on previous work with one-dimensional (1-D)
      simulations, the work reported here measured error variance for single-step and
      accumulated displacement estimates using two-dimensional (2-D) numerical
      simulations of ultrasound echo signals, subjected to both normal and axial shear
      strain as well as electronic noise. Previous results from 1-D simulations were
      confirmed, showing that errors due to electronic noise are negatively correlated
      between steps and accumulate slowly, while errors due to strain are positively
      correlated and accumulate quickly. These properties hold for both normal and
      axial shear strain. An analysis of 2-D kernel size for tissue under normal and
      axial shear strain was also performed. Under axial shear strain, error variance
      tends to increase with larger lateral kernel sizes but decrease for larger axial
      kernel sizes; the opposite relationship holds under normal strain. A combination
      of these two types of strain limits the practical kernel size in both dimensions.

PMID- 24275540
TI  - Selenoprotein S is a marker but not a regulator of endoplasmic reticulum stress
      in intestinal epithelial cells.
AB  - Selenoproteins are candidate mediators of selenium-dependent protection against
      tumorigenesis and inflammation in the gut. Expression and roles of only a limited
      number of intestinal selenoproteins have been described so far. Selenoprotein S
      (SelS) has been linked to various inflammatory diseases and is suggested to be
      involved in endoplasmic reticulum (ER) homeostasis regulation and antioxidative
      protection in a cell-type-dependent manner, but its protein expression,
      regulation, and function in the gut are not known. We here analyzed the
      expression and localization of SelS in the healthy and inflamed gut and studied
      its regulation and function in intestinal epithelial cell lines. SelS was
      expressed in the intestinal epithelium of the small and large intestine and
      colocalized with markers of Paneth cells and macrophages. It was upregulated in
      inflamed ileal tissue from Crohn's disease patients and in two models of
      experimental colitis in mice. We detected SelS in colorectal cell lines, where it
      colocalized with the ER marker calnexin. SelS protein expression was unaffected
      by enterocytic differentiation but increased in response to selenium
      supplementation and after treatment with the ER stress inducer tunicamycin. On
      the other hand, depletion of SelS in LS174T, HT29, and Caco-2 cells by RNA
      interference did not cause or modulate ER stress and had no effect on hydrogen
      peroxide-induced cell death. In summary, we introduce SelS as a novel marker of
      Paneth cells and intestinal ER stress. Although it is upregulated in Crohn's
      disease, its role in disease etiology remains to be established. 

PMID- 24275542
TI  - Ticlopidine and clopidogrel, sometimes combined with aspirin, only minimally
      increase the surgical risk in renal transplantation: a case-control study.
AB  - BACKGROUND: Patients undergoing kidney transplantation are sometimes being
      treated with antiplatelet agents such as ticlopidine or clopidogrel. Some teams
      refuse to wait-list these patients for fear of bleeding during transplant
      surgery. METHODS: We retrospectively reviewed the records of 702 adult patients
      with a kidney transplant alone between 2000 and 2010. Nineteen (2.7%) patients
      were taking clopidogrel or ticlopidine when called in for transplantation.
      Furthermore, 10 of these 19 patients were also taking low-dose aspirin (ASA). We
      compared the risk of bleeding peri- and postoperatively, and the occurrence of
      cardiovascular complications within 30 days after renal transplantation between
      19 cases and 39 controls randomly selected within the cohort. RESULTS: Platelets
      were administered to 7 cases (37%) versus 0 controls (P<0.001). A single case
      (5.3%) presented with significant bleeding during surgery following an
      implantation biopsy, and required 4 red bood cell (RBC) units. During the first
      day, 3 of the 19 cases (16%) and 1 of the 39 controls required RBC (P=0.1). No
      reoperation was performed for bleeding. After the transplant, clopidogrel or
      ticlopidine was resumed in only two patients. The platelet count and haemoglobin
      were similar between cases and controls at Day 30. No cardiovascular event
      occurred in cases or controls during the first month post-transplantation. At 5
      years, graft and patient survival was similar in cases and controls. CONCLUSIONS:
      Clopidogrel and ticlopidine, sometimes in combination with ASA, are associated
      with a low risk of bleeding during renal transplantation and does not seem to be
      a contraindication for renal transplant surgery.

PMID- 24275541
TI  - Role of the enteric microbiota in intestinal homeostasis and inflammation.
AB  - The mammalian intestine encounters many more microorganisms than any other tissue
      in the body thus making it the largest and most complex component of the immune
      system. Indeed, there are greater than 100 trillion (10(14)) microbes within the
      healthy human intestine, and the total number of genes derived from this diverse
      microbiome exceeds that of the entire human genome by at least 100-fold. Our
      coexistence with the gut microbiota represents a dynamic and mutually beneficial
      relationship that is thought to be a major determinant of health and disease.
      Because of the potential for intestinal microorganisms to induce local and/or
      systemic inflammation, the intestinal immune system has developed a number of
      immune mechanisms to protect the host from pathogenic infections while limiting
      the inflammatory tissue injury that accompanies these immune responses. Failure
      to properly regulate intestinal mucosal immunity is thought to be responsible for
      the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD;
      Crohn disease, ulcerative colitis). An accumulating body of experimental and
      clinical evidence strongly suggests that IBD results from a dysregulated immune
      response to components of the normal gut flora in genetically susceptible
      individuals. The objective of this review is to present our current understanding
      of the role that enteric microbiota play in intestinal homeostasis and
      pathogenesis of chronic intestinal inflammation. 

PMID- 24275543
TI  - Polychlorinated biphenyl exposures and cognition in older U.S. adults: NHANES
      (1999-2002).
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitously present in humans
      because of their resistance to degradation and accumulation in fatty tissues.
      Data on neurotoxic effects in older adults are limited. OBJECTIVE: We examined
      the cross-sectional association between serum PCB concentrations and cognitive
      function in older adults from the general U.S. population. METHODS: We analyzed
      data from 708 respondents, 60-84 years of age, participating in the National
      Health and Nutrition Examination Survey (1999-2002). We used the summed
      concentrations of 12 lipid-standardized PCB congeners as the measure of exposure
      and assessed cognitive function with the Digit-Symbol Coding test. We adjusted
      analyses for age, education, race/ethnicity, and poverty/income ratio. RESULTS:
      The median concentration of lipid-standardized PCBs in serum was 271 ng/g
      (interquartile range, 193-399 ng/g). We found a significant interaction between
      dioxin-like PCB concentration and age in association with cognitive score
      (p=0.04). Among older individuals (70-84 years of age), a 100-ng/g increase in
      serum concentrations of dioxin-like PCBs was associated with a significantly
      lower cognitive score (-2.7 points; 95% CI: -5.1, -0.2; p=0.04); however, in
      younger individuals (60-69 years of age), there was a nonsignificant positive
      association (2.9 points; 95% CI: -1.8, 7.7; p=0.32). Among the older
      participants, the negative association was more pronounced in women than in men.
      CONCLUSION: Our findings support the hypothesis that PCB exposure has adverse
      cognitive effects even at levels generally considered to pose low or no risk,
      perhaps affecting mainly those of advanced age.

PMID- 24275544
TI  - Distal 10q monosomy: new evidence for a neurobehavioral condition?
AB  - Pure distal monosomy of the long arm of chromosome 10 is a rare cytogenetic
      abnormality. The location and size of the deletions described in this region are
      variable. Nevertheless, the patients share characteristic facial appearance,
      variable cognitive impairment and neurobehavioral manifestations. A Minimal
      Critical Region corresponding to a 600 kb Smallest Region of deletion Overlap
      (SRO) has been proposed. In this report, we describe four patients with a distal
      10q26 deletion, who displayed attention-deficit/hyperactivity disorders (ADHD).
      One of them had a marked behavioral profile and relatively preserved cognitive
      functions. Interestingly, the SRO was not included in the deleted segment of this
      patient suggesting that this deletion could contain candidate genes involved in
      the control of neurobehavioral functions. One of these candidates was the CALY
      gene, known for its association with ADHD patients and whose expression level was
      shown to be correlated with neurobehavioral disturbances in varying animal
      models. This report emphasizes the importance of the behavioral problems as a
      cardinal feature of the 10q microdeletion syndrome. Haploinsufficiency of CALY
      could play a crucial role in the development of the behavioral troubles within
      these patients. 

PMID- 24275545
TI  - The origin of half-metallicity in conjugated electron systems--a study on
      transition-metal-doped graphyne.
AB  - We studied the mechanism of half-metallicity (HM) formation in transition-metal
      doped conjugated carbon based structures by first-principles electronic structure
      simulations. It is found that the HM is a rather complex phenomenon, determined
      by the ligand field splitting of d-orbitals of the transition metal atoms, the
      exchange splitting and the number of valence electrons. Since most of the
      conjugated carbon based structures possess ligands with intermediate strength,
      the ordering of the d-orbital splitting is similar in all structures, and the HM
      properties evolve according to the number of valence electrons. Based on this
      insight we predict that Cr-, Fe- and Co-doped graphyne will show HM, while Mn-
      and Ni-doped graphyne will not. By tuning the number of valence electrons, we are
      thus able to control the emergence of HM and control the energy gaps evolving in
      the majority or minority spin channels. 

PMID- 24275546
TI  - Negative spinal bone mineral density changes and subclinical ovulatory
      disturbances--prospective data in healthy premenopausal women with regular
      menstrual cycles.
AB  - Subclinical ovulatory disturbances (anovulation or short luteal phases within
      normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels.
      Given that progesterone plays a bone formation role, subclinical ovulatory
      disturbances may be associated with bone loss or less than expected bone gain.
      Our purpose was to perform a meta-analysis of prospective studies in healthy
      premenopausal women to determine the overall relationship of subclinical
      ovulatory disturbances to change in bone mineral density. Two reviewers
      independently identified from serial literature searches 6 studies meeting
      inclusion criteria: a 2-year study in 114 young adult women, 2006-2009,
      Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto,
      Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia;
      an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study
      in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985
      1988, Vancouver, Canada. This meta-analysis included a combined sample size of
      473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47
      years. The percentage of women with ovulatory disturbances varied significantly
      from 13% to 82%. Women with more frequent ovulatory disturbances had more
      negative percentage changes in spine bone mineral density (weighted mean
      difference = -0.86; P = 0.040) for random-effects analysis. There was significant
      heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show
      that regularly menstruating women with more frequent ovulatory disturbances
      experience more negative changes in bone (approximately -0.9% per year). These
      cycles with silent estrogen/progesterone imbalance may be clinically important. 

PMID- 24275547
TI  - Corporal punishment in rural Colombian families: prevalence, family structure and
      socio-demographic variables.
AB  - OBJECTIVE: To reveal the prevalence of corporal punishment in a rural area of
      Colombia and its correlates to family structure and other socio-demographic
      variables. METHOD: A survey about childrearing and childcare was developed for
      this study, including a specific question about corporal punishment that was
      developed based on the Conflict Tactics Scale (CTS). Family structure was
      categorized as follows, based on previous literature: 'nuclear family,' 'single
      parent' family, 'extended family,' 'simultaneous family' and 'composed family.'
      RESULTS: Forty-one percent of the parents surveyed admitted they had used
      corporal punishment of their children as a disciplinary strategy. The type of
      family structure, the number of children living at home, the age of the children,
      the gender of the parent who answered the survey, and the age and gender of the
      partner were significant predictors of corporal punishment. CONCLUSION: Family
      structure is an important variable in the understanding of corporal punishment,
      especially in regard to nuclear families that have a large number of children and
      parents who started their parental role early in life.

PMID- 24275548
TI  - The dimensional structure of posttraumatic stress symptomatology in 323,903 U.S.
      veterans.
AB  - There is ongoing debate regarding the optimal dimensional structure of
      posttraumatic stress disorder symptomatology. A better understanding of this
      structure has significant implications, as it can provide more refined phenotypic
      measures for use in studies of the etiology and neurobiology of PTSD, as well as
      for use as endpoints in treatment studies of this disorder. In this study we
      analyzed the dimensional structure of PTSD symptomatology, as assessed using the
      PTSD Symptom Checklist-Military Version in 323,903 Veterans. Confirmatory factor
      analyses were used to compare two 4-factor models and a newly proposed 5-factor
      model to the 3-factor DSM-IV model of PTSD symptom dimensionality. To evaluate
      the external validity of the best-fitting model, we then conducted a structural
      equation model examining how the symptom dimensions of this model related to
      diagnoses of depression, anxiety, and substance use disorder. Results indicated
      that a newly proposed 5-factor 'dysphoric arousal' model comprised of separate re
      experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptom
      clusters provided a significantly better fit to the data compared to the DSM-IV
      and the two alternative four-factor models. External validity analyses revealed
      that numbing symptoms were most strongly related to diagnoses of depression and
      substance use disorder, and that dysphoric arousal symptoms were most strongly
      related to a diagnosis of anxiety disorder. Thus the dimensional structure of
      PTSD may be best represented by five symptom dimensions. The clinical
      implications of these results and implications for further refinement of extant
      PTSD assessment instruments are discussed. 

PMID- 24275549
TI  - Higher risk of developing major depression and bipolar disorder in later life
      among adolescents with asthma: a nationwide prospective study.
AB  - OBJECTIVE: Previous studies have suggested an immunological dysfunction in mood
      disorders, but rarely have investigated the temporal association between allergic
      diseases and mood disorders. Using the Taiwan National Health Insurance Research
      Database, we attempted to investigate the association between asthma in early
      adolescence and the risk of unipolar depression and bipolar disorder in later
      life. METHODS: In all, 1453 adolescents with asthma aged between 10 and 15 years
      and 5812 age-/gender-matched controls were selected in 1998-2000. Subjects with
      unipolar depression and bipolar disorder that occurred up to the end of follow-up
      (December 31 2010) were identified. RESULTS: Adolescents with asthma had a higher
      incidence of major depression (2.8% vs. 1.1%, p < 0.001), any depressive disorder
      (6.1% vs. 2.6%, p < 0.001), and bipolar disorder (1.0% vs. 0.3%, p < 0.001) than
      the control group. Cox regression analysis showed that asthma in early
      adolescence was associated with an increased risk of developing major depression
      (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.14-2.89), any
      depressive disorder (HR: 1.74, 95% CI: 1.27-2.37), and bipolar disorder (HR:
      2.27, 95% CI: 1.01-5.07), after adjusting for demographic data and comorbid
      allergic diseases. DISCUSSION: Adolescents with asthma had an elevated risk of
      developing mood disorders in later life. Further studies would be required to
      investigate the underlying mechanisms for this comorbid association and elucidate
      whether prompt intervention for asthma would decrease the risk of developing mood
      disorders.

PMID- 24275550
TI  - The rearrangement of filamentous actin in mossy fiber synapses in
      pentylenetetrazol-kindled C57BL/6 mice.
AB  - Chemical kindling, as an experimental model of epileptogenesis, is induced by
      repetitive administration of subconvulsive amount of excitatory drugs. Kindled
      mice do not typically display spontaneous recurrent seizures, but are instead
      characterized by enhanced seizure susceptibility to convulsive stimulations. In
      order to provide insights into the aberrant synaptic plasticity during kindling,
      this study investigated the effect of pentylenetetrazol (PTZ) kindling on
      filamentous actin (F-actin) in mossy fiber synapses in C57BL/6 mice. Phalloidin
      labeling of F-actin showed that F-actin puncta were increased in number in the
      stratum lucidum of CA3 region in the hippocampus after kindling. The
      rearrangement of F-actin seemed to occur presynaptically, since synapsin I, a
      specific marker for mossy fiber terminals, was also up-regulated. Such subtle
      structural modifications occurring in the synapses are thought to contribute to
      the long-lasting increased sensitivity in the PTZ-kindled C57BL/6 mice. 

PMID- 24275551
TI  - Leptin enhances the secretion of interleukin (IL)-18, but not IL-1beta, from
      human monocytes via activation of caspase-1.
AB  - Circulating levels of leptin are elevated in type-2 diabetes mellitus (T2DM) and
      leptin plays a role in immune responses. Elevated circulating IL-18 levels are
      associated with clinical complications of T2DM. IL-18 regulates cytokine
      secretion and the function of a number of immune cells including T-cells,
      neutrophils and macrophages and as such has a key role in immunity and
      inflammation. Pro-inflammatory monocytes exhibiting elevated cytokine secretion
      are closely associated with inflammation in T2DM, however, little is known about
      the role of leptin in modifying monocyte IL-18 secretion. We therefore aimed to
      investigate the effect of leptin on IL-18 secretion by monocytes. We report
      herein that leptin increases IL-18 secretion in THP-1 and primary human monocytes
      but has no effect on IL-18mRNA. Leptin and LPS signalling in monocytes occurs by
      overlapping but distinct pathways. Thus, in contrast to a strong stimulation by
      LPS, leptin has no effect on IL-1betamRNA levels or IL-1beta secretion. In
      addition, LPS stimulates the secretion of IL-6 but leptin did not whereas both
      treatments up regulate IL-8 secretion from the same cells. Although leptin (and
      LPS) has a synergistic effect with exogenous ATP on IL-18 secretion in both THP-1
      and primary monocytes, experiments involving ATP assays and pharmacological
      inhibition of ATP signalling failed to provide any evidence that endogenous ATP
      secreted by leptin-stimulated monocytes was responsible for enhancement of
      monocyte IL-18 secretion by leptin. Analysis of the action of caspase-1 revealed
      that leptin up regulates caspase-1 activity and the effect of leptin on IL-18
      release is prevented by caspase-1 inhibitor (Ac-YVAD-cmk). These data suggest
      that leptin activates IL-18 processing rather than IL-18 transcription. In
      conclusion, leptin enhances IL-18 secretion via modulation of the caspase-1
      inflammasome function and acts synergistically with ATP in this regard. This
      process may contribute to aberrant immune responses in T2DM and other conditions
      of hyperleptinemia. 

PMID- 24275553
TI  - HIV protease inhibitors and onset of cardiovascular diseases: a central role for
      oxidative stress and dysregulation of the ubiquitin-proteasome system.
AB  - The successful roll-out of highly active antiretroviral therapy (HAART) has
      extended life expectancy and enhanced the overall well-being of HIV-positive
      individuals. There are, however, increased concerns regarding HAART-mediated
      metabolic derangements and its potential risk for cardiovascular diseases (CVD)
      in the long-term. Here certain classes of antiretroviral drugs such as the HIV
      protease inhibitors (PIs) are strongly implicated in this process. This article
      largely focuses on the direct PI-linked development of cardio-metabolic
      complications, and reviews the inter-linked roles of oxidative stress and the
      ubiquitin-proteasome system (UPS) as key mediators driving this process. It is
      proposed that PIs trigger reactive oxygen species (ROS) production that leads to
      serious downstream consequences such as cell death, impaired mitochondrial
      function, and UPS dysregulation. Moreover, we advocate that HIV PIs may also
      directly lower myocardial UPS function. The attenuation of cardiac UPS can
      initiate transcriptional changes that contribute to perturbed lipid metabolism,
      thereby fueling a pro-atherogenic milieu. It may also directly alter ionic
      channels and interfere with electrical signaling in the myocardium. Therefore HIV
      PI-induced ROS together with a dysfunctional UPS elicit detrimental effects on
      the cardiovascular system that will eventually result in the onset of heart
      diseases. Thus while HIV PIs substantially improve life expectancy and quality of
      life in HIV-positive patients, its longer-term side-effects on the cardiovascular
      system should lead to a) greater clinical awareness regarding its benefit-harm
      paradigm, and b) the development and evaluation of novel co-treatment strategies.

PMID- 24275554
TI  - Growth/differentiation factor 1 alleviates pressure overload-induced cardiac
      hypertrophy and dysfunction.
AB  - Pathological cardiac hypertrophy is a major risk factor for developing heart
      failure, the leading cause of death in the world. Growth/differentiation factor 1
      (GDF1), a transforming growth factor-beta family member, is a regulator of cell
      growth and differentiation in both embryonic and adult tissues. Evidence from
      human and animal studies suggests that GDF1 may play an important role in cardiac
      physiology and pathology. However, a critical role for GDF1 in cardiac
      remodelling has not been investigated. Here, we performed gain-of-function and
      loss-of-function studies using cardiac-specific GDF1 knockout mice and transgenic
      mice to determine the role of GDF1 in pathological cardiac hypertrophy, which was
      induced by aortic banding (AB). The extent of cardiac hypertrophy was evaluated
      by echocardiographic, hemodynamic, pathological, and molecular analyses. Our
      results demonstrated that cardiac specific GDF1 overexpression in the heart
      markedly attenuated cardiac hypertrophy, fibrosis, and cardiac dysfunction,
      whereas loss of GDF1 in cardiomyocytes exaggerated the pathological cardiac
      hypertrophy and dysfunction in response to pressure overload. Mechanistically, we
      revealed that the cardioprotective effect of GDF1 on cardiac remodeling was
      associated with the inhibition of the MEK-ERK1/2 and Smad signaling cascades.
      Collectively, our data suggest that GDF1 plays a protective role in cardiac
      remodeling via the negative regulation of the MEK-ERK1/2 and Smad signaling
      pathways. 

PMID- 24275556
TI  - Circulating microparticles from obstructive sleep apnea syndrome patients induce
      endothelin-mediated angiogenesis.
AB  - Microparticles are deemed true biomarkers and vectors of biological information
      between cells. Depending on their origin, the composition of microparticles
      varies and the subsequent message transported by them, such as proteins, mRNA, or
      miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating
      microparticles are associated with endothelial dysfunction by reducing
      endothelial-derived nitric oxide production. Here, we have analyzed the potential
      role of circulating microparticles from OSAS patients on the regulation of
      angiogenesis and the involved pathway. VEGF content carried by circulating
      microparticles from OSAS patients was increased when compared with microparticles
      from non-OSAS patients. Circulating microparticles from OSAS patients induced an
      increase of angiogenesis that was abolished in the presence of the antagonist of
      endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased
      in human endothelial cells treated by OSAS microparticles. We highlight that
      circulating microparticles from OSAS patients can modify the secretome of
      endothelial cells leading to angiogenesis. 

PMID- 24275555
TI  - Peri-conceptional obesogenic exposure induces sex-specific programming of disease
      susceptibilities in adult mouse offspring.
AB  - Vulnerability of the fetus upon maternal obesity can potentially occur during all
      developmental phases. We aimed at elaborating longer-term health outcomes of
      fetal overnutrition during the earliest stages of development. We utilized Naval
      Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational
      obesity and followed offspring outcomes in the absence of any postnatal
      obesogenic influences. Male adult offspring developed overweight, insulin
      resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these
      features were not observed in females. Instead, they showed impaired fasting
      glucose and a reduced fat mass and adipocyte size. Influences of the interaction
      of maternal diet*sex concerned offspring genes involved in fatty liver disease,
      lipid droplet size regulation and fat mass expansion. These data suggest that a
      peri-conceptional obesogenic exposure is sufficient to shape offspring gene
      expression patterns and health outcomes in a sex- and organ-specific manner,
      indicating varying developmental vulnerabilities between sexes towards metabolic
      disease in response to maternal overnutrition. 

PMID- 24275558
TI  - Neospora caninum and Toxoplasma gondii: relationship between hepatic lesions,
      cytological and biochemical analysis of the cavitary liquid during the acute
      phase of the diseases in experimental models.
AB  - The objective of this study was to evaluate the pathogenesis of ascites in mice
      infected with Toxoplasma gondii and gerbils infected with Neospora caninum during
      the acute phase disease. For that, 12 gerbils [Experiment I: not infected/control
      (n=6) and infected (n=6)] and 12 mice [Experiment II: control (n=6) and infected
      (n=6)] were used. Infected gerbils and mice showed marked ascites on days 5-7
      post-infection (PI), while the not-infected animals had not ascites. Peritoneal
      liquid was collected from the all mice with uninfected animals receiving 1.5mL of
      saline solution into their abdominal cavity, allowing the recovery of cavity
      liquid. As a result, it was possible to observe differences in physics, chemistry
      and cytological analysis of the fluid cavity of animals infected with N. caninum
      and T. gondii, when they were compared with uninfected animals, as well as
      between animals experimentally infected. Additionally both, N. caninum and T
      gondii, caused an increase in the levels of nitric oxide (NOx-nitrate/nitrite),
      protein oxidation (AOPP) and lipid peroxidation (TBARS), while serum total
      protein and albumin were reduced in infected gerbils and mice. Gerbils infected
      with N. caninum showed multiple large cells with multilobulated nucleus, lytic
      necrosis and abundant amount of eosinophilic cytoplasm into the hepatic
      parenchyma. By the other hand, mice infected with T. gondii developed myriad foci
      of lytic necrosis combined with tachyzoites and cysts containing bradyzoites in
      liver. Both experimental models for N. caninum and T. gondii showed inflammatory
      foci and tachyzoites the peritoneum, which could be a major cause of ascites.
      Toxoplasmosis and neosporosis were able to cause clinical signs in experimental
      models with similar alterations in peritoneal fluid; however the toxoplasmosis
      histological changes were much more evident. Therefore, the pathogenesis of
      ascites appears to be directly related to liver damage, which strongly suggests
      alteration in the normal production of proteins as observed in this study, along
      with peritonitis. 

PMID- 24275557
TI  - Antifilarial effects of polyphenol rich ethanolic extract from the leaves of
      Azadirachta indica through molecular and biochemical approaches describing
      reactive oxygen species (ROS) mediated apoptosis of Setaria cervi.
AB  - Lymphatic filariasis, a global cause of morbidity needs much more attention in
      developing potent therapeutics that can be effective against both microfilariae
      (mf) and adults. Efficient botanicals that can induce apoptosis of filarial
      parasites possibly can provide a direction towards developing new class of
      antifilarials. In this work we have evaluated the antifilarial efficacy of an
      optimized polyphenol rich ethanolic extract of Azadirachta indica leaves (EEA).
      A. indica A. Juss has been widely used in the traditional Indian medicinal system
      'Ayurveda' for the treatment of a variety of ailments. A thorough investigation
      towards biochemical and molecular mechanisms describing ROS mediated apoptosis in
      Setaria cervi was performed. Motility reduction, MTT reduction assay and dye
      exclusion test have confirmed the micro- and macrofilaricidal potential of EEA.
      Alterations were visible in mf and trichrome stained section of EEA-treated adult
      worms. We have found cellular disturbances in EEA-treated parasites characterized
      by chromatin condensation, in situ DNA fragmentation and nucleosomal DNA
      laddering. Depletion in worm GSH level and elevation in parasite GST, SOD,
      catalase, GPx and superoxide anion indicated the generation of ROS. Our results
      provided experimental evidence supporting that EEA causes a decreased expression
      of anti-apoptotic genes and increased pro-apoptotic gene expression at the level
      of both transcription and translation. Here we are reporting for the first time
      that antifilarial activity of EEA is mediated by ROS up regulation and apoptosis.

PMID- 24275559
TI  - Arthrodesis of the thumb interphalangeal joint and finger distal interphalangeal
      joints with a headless compression screw.
AB  - PURPOSE: To study the results of using a small, headless compression screw
      (AcuTwist) for thumb interphalangeal (IP) joint and finger distal interphalangeal
      (DIP) joint arthrodeses. METHODS: Between November 2007 and January 2012, 48
      primary arthrodeses of the thumb IP joint or DIP joint in the other digits were
      performed in 29 consecutive patients with AcuTwist devices. Indications for
      arthrodesis included 19 cases of osteoarthritis in 25 fingers, 3 cases of lupus
      in 9 fingers, 2 cases of post-traumatic osteoarthritis in 2 fingers, and 1 case
      and finger each of acute trauma, neuromuscular disorder, postinfectious
      osteoarthritis, boutonniere deformity, and Dupuytren contracture. Charts were
      reviewed for clinical data, and radiographs were assessed for alignment and
      healing. RESULTS: Age averaged 59 years and follow-up averaged 12 months (range,
      2-50 mo). Union occurred in 43 out of 46 fingers (94%). There were no cases of
      nail deformity, wound complications, tip hypersensitivity, or clinically notable
      malalignment. Three arthrodeses failed to fuse, including 2 asymptomatic
      nonunions and 1 fixation loss requiring revision with autograft. The complication
      rate was 9%. CONCLUSIONS: Distal digital joint arthrodesis with the AcuTwist
      resulted in a fusion rate of 94% with a complication rate of 9%. Our rate of
      fusion compares favorably with prior series using other methods of fixation. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24275560
TI  - Enabling variable-stiffness hand rehabilitation orthoses with dielectric
      elastomer transducers.
AB  - Patients affected by motor disorders of the hand and having residual voluntary
      movements of fingers or wrist can benefit from self-rehabilitation exercises
      performed with so-called dynamic hand splints. These systems consist of orthoses
      equipped with elastic cords or springs, which either provide a sustained stretch
      or resist voluntary movements of fingers or wrist. These simple systems are
      limited by the impossibility of modulating the mechanical stiffness. This
      limitation does not allow for customizations and real-time control of the
      training exercise, which would improve the rehabilitation efficacy. To overcome
      this limitation, 'active' orthoses equipped with devices that allow for
      electrical control of the mechanical stiffness are needed. Here, we report on a
      solution that relies on compact and light-weight electroactive elastic
      transducers that replace the passive elastic components. We developed a variable
      stiffness transducer made of dielectric elastomers, as the most performing types
      of electromechanically active polymers. The transducer was manufactured with a
      silicone film and tested with a purposely-developed stiffness control strategy
      that allowed for electrical modulations of the force-elongation response. Results
      showed that the proposed new technology is a promising and viable solution to
      develop electrically controllable dynamic hand orthoses for hand rehabilitation. 

PMID- 24275561
TI  - The mechanical and material properties of elderly human articular cartilage
      subject to impact and slow loading.
AB  - The mechanical properties of articular cartilage vary enormously with loading
      rate, and how these properties derive from the composition and structure of the
      tissue is still unclear. This study investigates the mechanical properties of
      human articular cartilage at rapid rates of loading, compares these with
      measurements at slow rates of loading and explores how they relate to the gross
      composition of the tissue. Full-depth femoral head cartilage biopsies were
      subjected to a slow, unconfined compression test followed by an impact at an
      energy of 78.5mJ and velocity 1.25ms(-1). The modulus was calculated from the
      slope of the loading curve and the coefficient of restitution from the areas
      under the loading and unloading curves. Tissue composition was measured as water,
      collagen and glycosaminoglycan contents. The maximum dynamic modulus ranged from
      25 to 150MPa. These values compared with 1-3MPa measured during quasi-static
      loading. The coefficient of restitution was 0.502 (0.066) (mean (standard
      deviation)) and showed no site variation. Water loss was not detectable.
      Composition was not strongly associated with modulus; water and collagen contents
      together predicted about 25% of the variance in modulus. 

PMID- 24275562
TI  - Trypsin-catalyzed tandem reaction: one-pot synthesis of 3,4-dihydropyrimidin
      2(1H)-ones by in situ formed acetaldehyde.
AB  - A simple, mild, one-pot tandem method catalyzed by trypsin was developed for the
      synthesis of 3,4-dihydropyrimidin-2(1H)-ones by the Biginelli reaction of urea,
      beta-dicarbonyl compounds, and in situ-formed acetaldehyde. Trypsin was found to
      display dual promiscuous functions to catalyze transesterification and the
      Biginelli reaction in sequence. 

PMID- 24275563
TI  - Evolution of electronic and magnetic properties in four polytypes of BaRuO3: a
      first-principles study.
AB  - Using density functional theory, we explore the evolution of the electronic and
      magnetic properties of BaRuO3 in four different phases, 9R, 4H, 6H and 3C,
      obtained by synthesizing under different pressure conditions. The four different
      phases differ in the differential proportion of hexagonal versus cubic close
      stacking of the BaO3 layers, leading to important changes in the structure. By
      computing the electronic and magnetic properties of the four different phases,
      and the optical properties of 4H and 9R phases, we find that density functional
      based calculations are to a large extent able to explain the change in properties
      of the four different polytypes. 

PMID- 24275564
TI  - Cutaneous leishmaniasis in a patient receiving infliximab for psoriatic
      arthritis: treatment with cryotherapy and intralesional meglumine antimonate.

PMID- 24275565
TI  - Dermatofibroma of the face: a clinicopathologic study of 20 cases.
AB  - INTRODUCTION: Dermatofibroma is one of the most common benign skin tumors. It
      typically develops on the lower limbs between the third and fifth decade of life
      and is more common in women. Clinical diagnosis is often straightforward.
      Dermatofibromas are associated with a very low rate of local recurrence following
      excision. OBJECTIVES: To describe the clinical and histologic features of
      dermatofibroma of the face based on our experience. MATERIALS AND METHODS:
      Descriptive retrospective study of the clinicopathologic features of
      dermatofibromas of the face diagnosed at the dermatology department of Hospital
      General Universitario de Valencia between 1990 and 2012. RESULTS: Twenty cases of
      dermatofibroma of the face (1.11% of all dermatofibromas diagnosed) were studied.
      The age at onset varied widely, from 28 to 84 years. The mean age at onset was
      57.15 years and the median was 54 years. There were 11 women and 9 men. Mean
      follow-up was 83 months and there were no local recurrences. All the tumors were
      confined to the papillary and reticular dermis and the storiform pattern was the
      most common growth pattern observed. CONCLUSIONS: This study of facial
      dermatofibromas diagnosed at our hospital over a period of 22 years suggests that
      the face is an uncommon site but that dermatofibromas in this location behave
      similarly to those occurring elsewhere on the body.

PMID- 24275566
TI  - Non-specific immune stimulation in respiratory tract infections. Separating the
      wheat from the chaff.
AB  - Parents of children suffering from recurrent respiratory infections can be
      persuaded by advertisements to pressure their family physicians and pediatricians
      for "immune-stimulating enhancements". However, the evidence base behind these
      immune stimulants is usually lacking. Often there is no peer-reviewed studies
      available that support claims made by "immune-booster" supplements. In this
      review, we critically analyze most of the marketed immuno-active drugs (including
      vitamin preparations, dietary supplements, homeopathic remedies, Ecchinacea,
      bacterial lysates, and probiotics) and identify the necessity to exclude an
      immunodeficiency in every child suffering from recurrent respiratory tract
      infections. 

PMID- 24275567
TI  - Acute pulmonary complications of sickle cell disease.
AB  - Acute pulmonary problems in sickle cell disease (SCD) patients, in particular
      acute chest syndrome (ACS), cause significant mortality and morbidity. It is
      important to differentiate ACS from pneumonia to avoid inappropriate or
      inadequate treatment. Asthma may increase the risk of ACS and co-morbid asthma
      and SCD are associated with worse patient outcomes and, in preclinical models,
      more severe inflammation. Recurrent wheezing, however, can occur in the absence
      of a diagnosis of asthma; it is likely due to SCD related inflammation and
      additional therapies than those that treat asthma may be required. Further
      research is merited to clarify these issues. 

PMID- 24275568
TI  - HCD-only fragmentation method balances peptide identification and quantitation of
      TMT-labeled samples in hybrid linear ion trap/orbitrap mass spectrometers.
AB  - Protein quantitation based on the generation of reporter ions from chemical
      labels is a widely used quantitative proteomics approach that enables measuring
      changes in protein abundance in response to biological perturbations. Isobaric
      labeling strategies at the MS2 level allow simultaneous measurements of different
      samples but it requires a fine-tuning of the collision energy used in HCD
      fragmentation to simultaneously obtain confident peptide identifications and
      highly sensitive and accurate quantitation. Although the recent development of
      dual CID/HCD fragmentation methods to circumvent these limitations, the fact is
      that many laboratories still use HCD-only methods for routine TMT protein
      quantitation experiments. Here, we have explored the effect of the collision
      energy on peptide identification and quantitation using HCD-only fragmentation
      methods on a linear ion trap/orbitrap mass spectrometer bearing an axial field
      HCD fragmentation cell. Our results using the HCD-only method show that a balance
      between the increase in the number of peptide identifications and the decrease in
      the precision of peptide quantitation is attained at a normalized collision
      energy of 40%. The HCD-only method at 40% does not only yield better results than
      those obtained using a higher collision energies, but it also outperforms the
      results obtained using the available CID/HCD dual method. BIOLOGICAL
      SIGNIFICANCE: In this work we have explored the effect of the collision energy on
      peptide identification and quantitation using HCD-only fragmentation methods on
      an Orbitrap Velos Pro mass spectrometer. Our results show that when using a HCD
      only method, a balance between the number of peptide identifications and the
      precision of peptide quantitation is attained at a normalized collision energy
      (NCE) of 40%. This contrast with the parameters routinely used in many
      laboratories, which are set at NCE 45%. The single HCD method at 40% does not
      only yield better results than those obtained using a collision energy of 45% but
      it also outperforms the results obtained using the available CID/HCD dual method.
      Therefore, we suggest that the single HCD method using the optimal NCE of 40% can
      therefore become the method of choice in routinely TMT protein quantitation
      experiments.

PMID- 24275569
TI  - An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
      phosphoproteome.
AB  - Protein phosphorylation is one of the most common post-translational
      modifications. It plays key roles in regulating diverse biological processes of
      liver tissues. To better understand the role of protein phosphorylation in liver
      functions, it is essential to perform in-depth phosphoproteome analysis of human
      liver. Here, an enzyme assisted reversed-phase-reversed-phase liquid
      chromatography (RP-RPLC) approach with both RPLC separations operated with
      optimized acidic mobile phase was developed. High orthogonal separation was
      achieved by trypsin digestion of the Glu-C generated peptides in the fractions
      collected from the first RPLC separation. The phosphoproteome coverage was
      further improved by using two types of instruments, i.e. TripleTOF 5600 and LTQ
      Orbitrap Velos. A total of 22,446 phosphorylation sites, corresponding to 6526
      nonredundant phosphoproteins were finally identified from normal human liver
      tissues. Of these sites, 15,229 sites were confidently localized with Ascore>=13.
      This dataset was the largest phosphoproteome dataset of human liver. It can be a
      public resource for the liver research community and holds promise for further
      biology studies. BIOLOGICAL SIGNIFICANCE: The enzyme assisted approach enabled
      the two RPLC separations operated both with optimized acidic mobile phases. The
      identifications from TripleTOF 5600 and Orbitrap Velos are highly complementary.
      The largest phosphoproteome dataset of human liver was generated.

PMID- 24275570
TI  - Is the use of haloperidol a safe and effective method of tranquilization for
      patients with psychosis-induced aggression or agitation?

PMID- 24275571
TI  - Ventilation with lower tidal volumes for critically ill patients without the
      acute respiratory distress syndrome: a systematic translational review and meta
      analysis.
AB  - PURPOSE OF REVIEW: There is convincing evidence for benefit from lung-protective
      mechanical ventilation with lower tidal volumes in patients with the acute
      respiratory distress syndrome (ARDS). It is uncertain whether this strategy
      benefits critically ill patients without ARDS as well. This manuscript
      systematically reviews recent preclinical studies of ventilation in animals with
      uninjured lungs, and clinical trials of ventilation in ICU patients without ARDS
      on the association between tidal volume size and pulmonary complications and
      outcome. RECENT FINDINGS: Successive preclinical studies almost without exception
      show that ventilation with lower tidal volumes reduces the injurious effects of
      ventilation in animals with uninjured lungs. This finding is in line with results
      from recent trials in ICU patients without ARDS, demonstrating that ventilation
      with lower tidal volumes has a strong potential to prevent development of
      pulmonary complications and maybe even to improve survival. However, evidence
      mostly comes from nonrandomized clinical trials, and concerns are expressed
      regarding unselected use of lower tidal volumes in the ICU, that is, in all
      ventilated critically ill patients, since this strategy could also increase needs
      for sedation and/or neuromuscular blockade, and maybe even cause respiratory
      muscle fatigue. These all then could in fact worsen outcome, possibly
      counteracting the beneficial effects of ventilation with lower tidal volumes.
      SUMMARY: Ventilation with lower tidal volumes protects against pulmonary
      complications, but well-powered randomized controlled trials are urgently needed
      to determine whether this ventilation strategy truly benefits all ventilated ICU
      patients without ARDS.

PMID- 24275572
TI  - Alterations in carbohydrate and protein metabolism in silver catfish (Rhamdia
      quelen) exposed to cadmium.
AB  - Changes in carbohydrate and protein metabolism were studied in silver catfish
      Rhamdia quelen exposed to cadmium (0; 0.236 or 0.414 mg/L) during 7 and 14 days.
      After exposure time the fish were exposed to recovery period (water without
      cadmium), during 7 and 14 days. Different alterations in the metabolic parameters
      were observed such as an increase in lactate, protein, amino acid and ammonia
      levels as well as a reduction in glucose values after the exposure periods in
      liver. In muscle, glycogen and glucose values enhanced after cadmium exposure at
      both concentrations for 7 days; however, at 0.414 mg/L cadmium, protein levels
      decreased while amino acids and ammonia levels enhanced. An increase in the
      lactate values was found in plasma after 7 days of exposure and a reduction in
      the lactate, glucose and protein levels occurred after 14 days of exposure.
      Results indicated that the metabolic alterations after cadmium exposure were
      dependent on the tissue type and exposure time. Cadmium exposure for 14 days and
      recovery period also of 14 days seem to be less harmful to the liver and muscle.
      However, even after recovering from some changes, fish health may be affected
      making them more sensitive to some environmental changes.

PMID- 24275573
TI  - Risk factors and criteria predicting early graft loss after adult-to-adult living
      donor liver transplantation.
AB  - BACKGROUND: Because deceased liver donors are scarce, adult-to-adult living donor
      liver transplantation (LDLT) is considered a suitable alterative. However, LDLT
      grafts are usually partial, resulting in a higher risk of early graft loss (EGL).
      The aim of the present study was to identify the risk factors and criteria
      predicting EGL after LDLT. METHODS: We retrospectively analyzed 178 consecutive
      adults who underwent LDLT. The recipients were divided into two groups as
      follows: group I, wherein patients showed graft survival longer than 3 mo after
      LDLT (n = 164), and group II, wherein graft loss occurred within 3 mo after
      transplantation (n = 14). RESULTS: Univariate analysis showed various risk
      factors; however, only the preoperative model for end-stage liver disease score,
      the presence of obvious pretransplant portal hypertension, and intraoperative
      blood loss were identified as independent predictors of EGL by multivariate
      analysis. After LDLT, significant differences were observed between the groups in
      the fold change in total bilirubin levels over postoperative day (POD) 1 (TBIL
      f1) and in the international normalized ratio over POD 1 (INR-f1). The
      combination of TBIL-f1 and INR-f1 on POD 10 was found to be a strong EGL
      predictor. Furthermore, a minimum indocyanine green (ICG) clearance rate constant
      K (m-KICG) <0.100/min after POD 3 was found to be the strongest predictor of EGL
      (sensitivity, 100%; specificity, 97.2%). CONCLUSIONS: The postoperative m-KICG
      and combination of TBIL-f1 and INR-f1 on POD 10 were useful predictors of EGL;
      moreover, m-KICG was superior and is expected to be especially useful for
      ensuring timely retransplantation.

PMID- 24275575
TI  - RE: The rare sugar D-allose has a reducing effect against ischemia-reperfusion
      injury on the rat abdominal skin island flap model: a molecular mechanism.

PMID- 24275574
TI  - The interaction between oxidative stress and mast cell activation plays a role in
      acute lung injuries induced by intestinal ischemia-reperfusion.
AB  - BACKGROUND: Both oxidative stress and mast cells are involved in acute lung
      injuries (ALIs) that are induced by intestinal ischemia-reperfusion (IIR). The
      aim of this study was to further investigate the interaction between oxidative
      stress and mast cells during the process of IIR-induced ALI. MATERIALS AND
      METHODS: Thirty adult Sprague-Dawley rats were randomly divided into five groups:
      sham, IIR, IIR + compound 48/80 (CP), N-acetylcysteine (NAC) + IIR, and NAC + IIR
      + CP. All rats except those in the sham group were subjected to 75 min of
      superior mesenteric artery occlusion, followed by 2 h of reperfusion. The rats in
      the NAC + IIR and NAC + IIR + CP groups were injected intraperitoneally with NAC
      (0.5 g/kg) for three successive days before undergoing IIR. The rats in the IIR +
      CP and NAC + IIR + CP groups were treated with CP (0.75 mg/kg), which was
      administered intravenously 5 min before the reperfusion. At the end of the
      experiment, lung tissue was obtained for pathologic and biochemical assays.
      RESULTS: IIR resulted in ALI, which was detected by elevated pathology scores, a
      higher lung wet-to-dry ratio, and decreased expression of prosurfactant protein C
      (P < 0.05). Concomitant elevations were observed in the expression levels of the
      nicotinamide adenine dinucleotide phosphate oxidase subunits p47(phox) and
      gp91(phox) and the levels of hydrogen peroxide and malondialdehyde. However,
      superoxide dismutase activity in the lung was reduced (P < 0.05). The level of
      interleukin 6, the activity of myeloperoxidase, and the expression of
      intercellular adhesion molecule 1 were also increased in the lung. IIR led to
      pulmonary mast cell degranulation and increases in the plasma and pulmonary beta
      hexosaminidase levels, mast cell counts, and tryptase expression in lung tissue.
      CP aggravated these conditions, altering the measurements further, whereas NAC
      attenuated the IIR-induced ALI and all biochemical changes (P < 0.05). However,
      CP abolished some of the protective effects of NAC. CONCLUSIONS: Oxidative stress
      and mast cells interact with each other and promote IIR-induced ALI.

PMID- 24275576
TI  - Role of non-MLC20 phosphorylation pathway in the regulation of vascular
      reactivity during shock.
AB  - BACKGROUND: Studies have shown that shock-induced vascular hyporeactivity is
      associated with the decrease in 20-kDa myosin light chain (MLC20)
      phosphorylation. Whether and how a non-MLC20 phosphorylation pathway participates
      in the regulation of vascular reactivity after shock is not known. METHODS: With
      superior mesentery artery (SMA) obtained from rats in hemorrhagic shock and
      hypoxia-treated SMA, the regulatory effect of platelet-derived growth factor
      (PDGF) on vascular reactivity and the roles of caldesmon, 27-kDa heat shock
      protein (HSP27), extracellular signal-regulated protein kinase (Erk), and p38
      mitogen-activated protein kinase (MAPK), the main molecules that are involved in
      the non-MLC20 phosphorylation pathway of the regulation of smooth-muscle
      contraction, were investigated. RESULTS: PDGF (40-100 ng/mL) increased the
      vascular reactivity after shock in a dose-dependent manner, whereas it did not
      increase the MLC20 phosphorylation in a dose-dependent manner. PDGF with
      concentration more than 60 ng/mL did not further increase the MLC20
      phosphorylation, whereas upregulated the phosphorylation of HSP27, Erk, and
      p38MAPK, and the activity of myosin adenosine triphosphatase in SMAs, and
      downregulated the phosphorylation of caldesmon. p38MAPK antagonist, SB203580, not
      only antagonized PDGF-induced increase in the phosphorylation of HSP27, but also
      antagonized PDGF-induced decrease in the phosphorylation of caldesmon, whereas
      Erk antagonist, PD98059, only antagonized PDGF-induced decrease in the
      phosphorylation of caldesmon. CONCLUSIONS: These findings suggested that a non
      MLC20 phosphorylation pathway participated in the regulation of vascular
      reactivity after shock. Caldesmon- and HSP27-mediated change in myosin adenosine
      triphosphatase activity and Erk and p38MAPK played an important role in this
      process. These findings may provide some potential targets for the treatment of
      vascular hyporeactivity after shock.

PMID- 24275577
TI  - Effects of olanzapine on the PR and QT intervals in patients with schizophrenia.

PMID- 24275578
TI  - MIR137 gene and target gene CACNA1C of miR-137 contribute to schizophrenia
      susceptibility in Han Chinese.
AB  - Recently, evidence has accumulated indicating that the MIR137 gene and the target
      gene CACNA1C of miR-137 might be two of the most robustly implicated genes in
      schizophrenia. In this study, we examined 33 single nucleotide polymorphisms
      (SNPs) located in two genes by performing an association analysis in a cohort of
      1430 schizophrenia patients and 1570 healthy Han Chinese control subjects. Single
      SNP association, sex-specific association and haplotype association analyses were
      performed. For the rs1625579 marker in MIR137 and the rs1006737 and rs4765905
      markers in CACNA1C, significant differences in the allele frequencies were found
      between the patients and controls (p=0.007949, p=0.013658 and p=0.013999,
      respectively), and the genotype association analysis for them suggested a similar
      pattern (p=0.023167, p=0.046623 and p=0.047824, respectively). Further analysis
      of the haplotype rs1006737-rs4765905-rs882194 in CACNA1C showed significant
      associations with schizophrenia (corrected global p<0.005), and two haplotypes
      (ACC and ACT) in the block were significantly increased in the patients. When the
      samples were analyzed separately by gender, we found no significant sex-specific
      associations in MIR137 and CACNA1C, which was similar to the results from the
      relevant haplotype association analysis in the female and male subgroups. We have
      provided new evidence supporting the association between MIR137 and CACNA1C and
      schizophrenia in the Han Chinese population. 

PMID- 24275579
TI  - Violence and violent victimization in people with severe mental illness in a
      rural low-income country setting: a comparative cross-sectional community study.
AB  - BACKGROUND: Violence perpetrated by and against people with severe mental illness
      (SMI) is important but rarely investigated in low- and middle income countries.
      OBJECTIVE: To compare the prevalence of perpetrated violence and violent
      victimization, and associated factors, in people with and without SMI in rural
      Ethiopia. METHOD: A random sub-sample of people with a standardized, clinician
      diagnosis of SMI (n=201) was recruited from an existing population-based study
      and compared to a group of unaffected individuals from the same neighborhood
      (n=200). The lifetime and 12-month prevalence of violence and violent
      victimization was measured using an adapted version of the McArthur Violence
      Interview. RESULT: Lifetime and 12-month prevalence of perpetrated violence in
      people with SMI (28.4% and 17.4%, respectively) was significantly higher than in
      the non-mentally ill comparison group (15.0% and 8.5%, respectively). Male
      gender, being literate and violent victimization were associated independently
      with violence in both groups. In people with SMI, violence was associated
      additionally with being unmarried, exposure to stressful life events and non
      response to medication. The prevalence of violent victimization was also
      significantly higher in people with SMI than those without SMI (60.7% vs. 41.5%).
      In people with SMI, violent victimization was associated with unemployment, non
      adherence to treatment and being a perpetrator of violence. CONCLUSIONS: Our
      finding of high levels of violence and violent victimization in people with SMI
      underscores the need to improve access to mental health services in this setting,
      as well as the urgent need to raise awareness about victimization of people with
      SMI.

PMID- 24275581
TI  - Should schizophrenia still be named so?

PMID- 24275580
TI  - Perinatal maternal life events and psychotic experiences in children at twelve
      years in a birth cohort study.
AB  - BACKGROUND: International studies indicate that the median prevalence of
      psychotic experiences in children is 7%. It has been proposed that environmental
      stress during pregnancy may affect the neurodevelopment of the foetus and lead to
      a vulnerability in the child to later stressors and psychopathology. AIM: In this
      study we explore the relationship between environmental stress during pregnancy
      and psychotic experiences in children in the general population at 12 years.
      METHODS: We analysed a birth cohort of 5038 children from the Avon Longitudinal
      Study of Parents and Children. Environmental stress was measured as life event
      exposure. Data on life events were collected on women during their pregnancy,
      whilst psychotic experiences in the offspring were assessed at age 12. RESULTS:
      There was a weak association between maternal exposure to life events and
      psychotic experiences at twelve years (crude OR 1.10 95% CI 1.02-1.18) per
      quartile of life event score. This association was not reduced after adjustment
      for socio-economic status, family history of schizophrenia, maternal education or
      birth weight but after adjustment for maternal anxiety and depression and smoking
      in early pregnancy there was no longer any evidence for an association (OR 1.01
      95% CI 0.93-1.10). CONCLUSION: This study provides some evidence to suggest that
      stressful life events may affect child psychotic experiences through effects on
      maternal psychopathology, and possibly physiology, during pregnancy.

PMID- 24275582
TI  - Age at initiation of amphetamine use and age at onset of psychosis: the
      Australian Survey of High Impact Psychosis.
AB  - Individuals with a psychotic disorder who had a premorbid history of amphetamine
      use (n=382) were analyzed in groups according to age of initiation to amphetamine
      (AIA) and mean number of years of duration of premorbid exposure to amphetamine
      (DPEA) was calculated. Univariate General Linear Models were used to test for
      group differences in age at onset of psychotic illness (AOI) and DPEA. Although a
      temporal direct relationship between AIA and AOI was detected (mean duration 5.3
      years), our findings suggested this association was spurious and better explained
      by a later initiation to amphetamine than to cannabis (by 2-3 years).

PMID- 24275583
TI  - Real-world effectiveness of antipsychotic monotherapy vs. polypharmacy in
      schizophrenia: to switch or to combine? A nationwide study in Hungary.
AB  - BACKGROUND: Leading guidelines recommend antipsychotic (AP) monotherapy for
      schizophrenia, nonetheless the combination of antipsychotics (polypharmacy) is
      common practice worldwide. We conducted a nationwide population-based study to
      investigate the comparative effectiveness of monotherapy versus polypharmacy in
      schizophrenia and other psychotic disorders. METHODS: Data was collected from the
      Hungarian National Health Insurance Fund's database and a non-interventional
      retrospective-prospective parallel arm study was designed with a monotherapy arm
      (MA, switch to a new antipsychotic after >60 days of monotherapy, N=5480) and a
      polypharmacy arm with two APs (PA, addition of a second antipsychotic after >60
      days of monotherapy, N=7901). The analyses focused on therapy changers, who
      started a new monotherapy or added a new AP to the existing one. Polypharmacy
      combinations with more than two APs were not investigated. Fourteen APs were
      investigated representing the majority of marketed antipsychotics of Hungary in
      the period of 1/2007-12/2009. The principal endpoint was the time to all-cause
      treatment discontinuation during a one-year observation period. Kaplan-Meier
      survival analysis and Cox proportional hazards model were applied with propensity
      score adjustment. RESULTS: The principal outcome measure time to all-cause
      discontinuation indicated superiority for monotherapy over polypharmacy for the
      majority of (oral and depot) second generation APs (SGAs). For first generation
      APs (FGAs), oral formulations did not show a difference between monotherapy and
      polypharmacy, while depot formulations exhibited polypharmacy advantage. For the
      four most frequently used oral SGAs, the median times to all-cause
      discontinuation for monotherapy and polypharmacy, respectively, were 192 and 100
      days for aripiprazole; 222 and 86 days for olanzapine; 176 and 91 days for
      quetiapine; and 157 and 93 days for risperidone. For mortality and
      hospitalization, a significant overall advantage of polypharmacy was detected.
      CONCLUSIONS: Our study provides evidence for the superiority of monotherapy over
      polypharmacy for SGAs in terms of all-cause treatment discontinuation in
      schizophrenia. Polypharmacy, however, was associated with a lower likelihood of
      mortality and hospitalizations. The finding that MA is superior to PA for long
      term sustained treatment whereas polypharmacy has advantage in mortality and
      psychiatric hospitalizations suggests that combination treatments may be more
      efficacious during exacerbation of psychotic symptoms.

PMID- 24275584
TI  - Exercise practices of young people at their first episode of psychosis.

PMID- 24275585
TI  - TCF4 gene polymorphism and cognitive performance in patients with first episode
      psychosis.
AB  - BACKGROUND: Single nucleotide polymorphisms in TCF4 gene have been consistently
      associated with schizophrenia in genome wide association studies, including the C
      allele of rs9960767. However, its exact role in modulating the schizophrenia
      phenotype is not known. AIMS: To comprehensively investigate the relationship
      between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients
      with first episode psychosis (FEP). METHODS: 173 patients with FEP received a
      comprehensive neurocognitive evaluation and were genotyped for rs9960767.
      Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using
      Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and
      substance abuse were included as covariates. RESULTS: Carriers of the risk allele
      had a statistically significant lower performance in the cognitive domain of
      Reasoning/Problem-Solving compared to non-carriers (F1,172=4.4, p=.038). There
      were no significant genotype effects on the other cognitive domains or general
      cognition. This effect on the Reasoning/Problem-Solving domain remained
      significant even when controlling for IQ (F1,172=4.3, p=.039). CONCLUSIONS:
      rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in
      the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A
      confirmation of this finding in a larger sample and including other TCF4
      polymorphisms will be needed to gain further validity of this result.

PMID- 24275587
TI  - Number and regional distribution of GAD65 mRNA-expressing interneurons in the rat
      hippocampal formation.
AB  - In rodent models for neuropsychiatric disorders reduced number of hippocampal
      interneurons have been reported, but the total number of GABAergic neurons in the
      normal rat hippocampus is yet unknown. We used in situ hybridization method to
      label the 65 isoform of glutamic acid decarboxylase (GAD65) and counted the
      number of GAD65 mRNA-expressing neurons along the entire septo-temporal axis of
      the hippocampus. We found that 2/3 of the interneurons were in Ammon's horn
      (61,590) and 1/3 in the dentate gyrus (28,000). We observed the following numbers
      in Ammon's horn: CA3 area 33,400, CA2 area 4,190, CA1 area 24,000 and in the
      dentate gyrus: 6,000 in the molecular and 9,000 in the granule cell layers and
      13,000 in the hilus. GAD65 mRNA-expressing neurons were significantly more
      numerous in dorsal than in ventral hippocampus. The ratio between interneurons
      and principal cells was lowest in the granule cell layer (0.9%) and highest in
      hilus (21%). In Ammon's horn this ratio was constant being 13% in CA3 and 8% in
      CA1-2 areas. In the entire hippocampal formation, the interneuron/principal cell
      ratio was 6%, with a significant difference between Ammon's horn (9.5%) and the
      dentate gyrus (2.8%) including the hilus. Such low ratios could suggest that even
      a limited loss of GABAergic neurons in the hippocampus may have a considerable
      functional impact. 

PMID- 24275588
TI  - The effect of partial food deprivation on the astroglia in the dorsal subnucleus
      of the lateral septum of the rat brain.
AB  - The effect of 40% partial food deprivation was studied on the
      immunohistochemically detectable amount of glial fibrillary acidic protein (GFAP)
      - the specific marker of astroglia - in the dorsal subnucleus of lateral septum
      (LS) of male, intact and ovariectomized (OVX) female rats. Animals were either
      fed ad libitum (control) or 40% food deprived for one week, then perfusion-fixed,
      their brains removed, and serial vibratome sections were processed for the
      immunocytochemical localization of GFAP. Computeraided densitometry was carried
      out on digital photographs.The results showed that ovariectomy alone did not
      exert any effect on the density of GFAPimmunoreactivity (GFAP-IR) as compared to
      the values detected in intact females. Food deprivation increased the density of
      GFAP in each experimental group. The difference was most pronounced in males,
      significant in females and much less in ovariectomized females. Parietal cortex
      chosen as reference area did not show any increase in the local GFAP-IR.It was
      previously shown that the dorsal subnucleus of the lateral septum reacts with
      plastic neurochemical changes to food deprivation. Our results prove that these
      changes affect not only neuronal but also glial elements. 

PMID- 24275586
TI  - Early DEtection of wEaring off in Parkinson disease: the DEEP study.
AB  - OBJECTIVE: Assessing the frequency of Wearing-Off (WO) in Parkinson's disease
      (PD) patients, and its impact on Quality of Life (QoL). METHODS: Consecutive
      ambulatory patients, who were on dopaminergic treatment for >= 1 year, were
      included in this multicentre, observational cross-sectional study. In a single
      visit, WO was diagnosed based on neurologist assessment as well as using the
      validated Italian version of a patient self-rated 19-question Wearing-Off
      Questionnaire (WOQ-19); WO was defined for scores >= 2. QoL was evaluated by the
      8-item Parkinson's Disease Questionnaire (PDQ-8). RESULTS: 617 subjects were
      included, with a mean anti-Parkinson treatment duration of 6.6 +/- 4.6 years,
      87.2% were on levodopa treatment. Neurologists identified presence of WO in 351
      subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self
      administered WOQ-19. In patients with a <2.5 years disease duration, WO was
      diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by
      the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were
      "slowness of movements" (55.8%) and "reduced dexterity" (48.8%). Younger age,
      female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and
      duration of anti-Parkinson treatment were found significantly associated with WO.
      The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms
      correlated with PDQ-8 total score. CONCLUSIONS: WO is common already at the early
      stages of PD and is underestimated by routine neurological clinical evaluation.
      The number of WO symptoms, both motor and non motor, increases along with disease
      duration and has a negative impact on patients QoL.

PMID- 24275589
TI  - FoxP2 and olfaction: divergence of FoxP2 expression in olfactory tubercle between
      different feeding habit bats.
AB  - FoxP2 is a member of the winged helix/forkhead class of transcription factors.
      Despite FoxP2 is found to have particular relevance to speech and language, the
      role of this gene is broader and not yet fully elucidated. In this study, we
      investigated the expression of FoxP2 in the brains of bats with different feeding
      habits (two frugivorous species and three insectivorous species). We found FoxP2
      expression in the olfactory tubercle of frugivorous species is significantly
      higher than that in insectivorous species. Difference of FoxP2 expression was not
      observed within each of the frugivorous or insectivorous group. The diverse
      expression patterns in olfactory tubercle between two kinds of bats indicate
      FoxP2 has a close relation with olfactory tubercle associated functions,
      suggesting its important role in sensory integration within the olfactory
      tubercle and such a discrepancy of FoxP2 expression in olfactory tubercle may
      take responsibility for the different feeding behaviors of frugivorous and
      insectivorous bats. 

PMID- 24275590
TI  - Cytotoxic and apoptotic functions of licofelone on rat glioma cells.
AB  - Gliomas are the largest group of central nervous system tumors and despite of
      clinical treatments death rate is very high. Inhibition of both cyclooxygenase
      and lipoxygenase pathways that take role in arachidonic acid metabolism prevents
      cancer development and induces apoptosis. One of the most promising compounds
      that blocks both of these pathways is licofelone. Using colchicine and 5
      fluorouracil as positive controls, we questioned whether licofelone affects the
      survival of rat glioma cell line (C6) and induces apoptosis in vitro. After
      growing the cells in culture, we determined viability with MT, apoptosis with
      flow cytometry and activity of caspase enzymes with real time PCR. All used doses
      of colchicine and 5-fluorouracil were cytotoxic and reduced the number of
      surviving C6 cells as much as 44% and 60%, respectively. Comparing to the
      control, treatments with 10, 50 and 100 MUM licofelone for 24 or 48 h did not
      influence C6 survival, however, 150, 200 and 250 MUM licofelone reduced the
      number of living cells by 58, 88 and 93%, respectively, and induced apoptosis of
      C6 cells in a dose and time dependent manner. Licofelone did not change the level
      of caspase-9, but increased the level of caspase-3. Comparing with 5-fluorouracil
      and colchicine, the present study reveals for the first time the possibility that
      licofelone possesses a strong dose and time dependent antiproliferative and
      proapoptotic properties on glioma cells. 

PMID- 24275591
TI  - Phenotypic comparison of four thalassemia model mice reconstructed from cryo
      banked embryos.
AB  - A major clinical feature of patients with thalassemia is growth retardation due
      to anemia, therefore, the hematological parameters, weanling weight and post
      weanling weight of pups obtained from vitrified warmed embryo transfers were
      studied for the first time in this report. Two-cell embryos of four transgenic
      (TG) thalassemic mouse lines (BKO, 654, E2, and E4) were produced by breeding
      four lines of TG thalassemic males to wild-type (WT) females (C57BL/6J) and were
      cryopreserved by vitrification in straws using 35% ethylene glycol. After
      transfer of vitrified-warmed embryos, hematological parameters, spleen index,
      weanling and post-weanling weight were determined in TG and WT viable pups. In
      the BKO and 654 mice significantly abnormal hematological parameters and spleen
      index were observed compared to WT, E2 and E4 mice. The weanling and post
      weanling weights of BKO and 654 pups were significantly less than that of the age
      matched WT pups. However, no significant differences in weanling and post
      weanling weight were found between WT and E2-TG or E4-TG pups. In conclusion, the
      four transgenic mice lines produced from cryopreserved embryo transfer retain the
      phenotype of the natural breeding mice indicating that these banked embryos are
      appropriate for thalassemia model productions.

PMID- 24275592
TI  - Impact of environmental and genetic factors on the scale shape of zebrafish,
      Danio rerio (Hamilton 1822): a geometric morphometric study.
AB  - Intraspecific morphological variability may reflect either genetic divergence
      among groups of individuals or response of individuals to environmental
      circumstances within the frame of phenotypic plasticity. Several studies were
      able to discriminate wild fish populations based on their scale shape. Here we
      examine whether the variations in the scale shape in fish populations could be
      related to genetic or environmental factors, or to both of them. In the first
      experiment, two inbred lines of zebrafish, Danio rerio (Hamilton 1822) reared
      under identical environmental conditions were compared. Secondly, to find out
      what effect environmental factors might have, offsprings were divided into two
      groups and reared on different diets for 12 weeks. Potential recovery of scales
      from an environmental effect was also assessed. Experimental groups could
      successfully be distinguished according to the shape of scales in both
      experiments, and the results showed that both genetic and environmental factors
      may notably influence scale shape. It was concluded that scale shape analysis
      might be used as an explanatory tool to detect potential variability of
      environmental influences impacting genetically homogeneous groups of fish.
      However, due to its sensitivity to environmental heterogeneity, the applicability
      of this technique in identifying intraspecific stock membership of fish could be
      limited. 

PMID- 24275593
TI  - Effect of cadmium pollution of atmospheric origin on field-grown maize in two
      consecutive years with diverse weather conditions.
AB  - The aim of the study was to analyse the effect of atmospheric cadmium (Cd)
      pollution of atmospheric origin in maize compared to a control without Cd
      pollution. The plant parameters investigated were the timing of phenological
      phases, leaf area index (LAI) and yield, while radiation and water regime
      parameters were represented by albedo (reflection grade) and evapotranspiration,
      respectively. In treatments with and without irrigation, Cd caused a significant
      reduction in LAI, accompanied by lower evapotranspiration. The mean annual albedo
      in the Cd-polluted treatment only rose to a moderate extent in 2011 (in 2010
      there was hardly any change), but changes within the year were more pronounced in
      certain phases of development. Cd led to greater reflection of radiation by
      plants during the vegetative phase, so the radiation absorption of the canopy was
      reduced leading to a lower level of evapotranspiration. In the dry, hot year of
      2011 maize plants in the non-irrigated treatments showed a substantial reduction
      in grain dry matter, but maize yield losses could be reduced by irrigation in
      areas exposed to Cd pollution. 

PMID- 24275594
TI  - Effect of electric arc furnace slag on growth and physiology of maize (Zea mays
      L.).
AB  - Basic slag, used in this study as a potential source of certain nutrients, is a
      byproduct of the production of steel in electric arc furnace (EAF). A pot
      experiment with two nutrient-poor substrates was conducted to investigate to
      compare the effect of EAF steel slag and fertilizers NPK + F e on growth and
      availability of specific nutrients to maize. Mineral content of both substrate
      and plant leaves, growth, chlorophyll fluorescence and photosynthetic pigments
      were measured following six weeks of cultivation. As steel slag also contains
      trace amounts of heavy metals, certain oxidative parameters (antioxidative enzyme
      activities and lipid peroxidation) were evaluated as well. The steel slag
      improved soil mineral composition, increased above ground maize biomass by
      providing Fe, Mn, Mg, K and partly P and improved photosynthetic parameters. The
      potential phytotoxicity of EAF slag containing substrates was not determined as
      evaluated by MDA (malondialdehyde), GR (glutathione reductase) and APX (ascorbate
      peroxidase) levels. The obtained results show that EAF steel slag is comparable
      to NPK + F e in supplying nutrients for maize growth, indicating the potential of
      EAF steel slag as an inexpensive and non-phytotoxic nutrient supplier especially
      in poor soils. 

PMID- 24275595
TI  - On the spectrophotometric determination of total phenolic and flavonoid contents.
AB  - Spectrophotometric assays assessing total phenol and flavonoid content in plant
      samples are cheaper and faster and thus more accessible methods than analytical
      chromatography techniques, although these identify compound categories rather
      than individual compounds. Most methods are used and are published in several
      varieties and their general (chemically unspecific) nature is often neglected.
      The aim of the present in vitro study was to compare five frequently used methods
      in terms of cross reactivity and sensitivity using pure phenolic substances. Test
      compounds were selected to represent categories of phenolic compounds of special
      interest in plant stress studies. Examining the classic Folin-Ciocalteu test we
      found that in addition to phenolics, it was also reactive to ascorbate. Three
      flavonoid assays were also examined. These are usually applied to quantify (i)
      flavonols using aluminium-chloride, (ii) flavanons and flavanonols using 2,4
      dinitrophenyl-hydrazine or (iii) flavanols using 4-dimethylamino-cinnamaldehyde.
      We found that all three methods were unaffected by the presence of ascorbate, but
      only the last one was specific to the group of compounds aimed at. Our results
      show that cross reactivities to various flavonoid groups should be taken into
      account when interpreting data from these assays. Methods utilizing the UV
      absorption of phenolic compounds were also tested and analyses of whole spectra
      were found more accurate than estimates based on absorptions at single
      wavelengths. 

PMID- 24275596
TI  - Interactions between naturally occurring antifungal agents.
AB  - Pairwise interactions between four antifungal compounds were studied. The beta
      1,3-glucan synthase inhibitor echinocandin B (ECB) showed synergistic effect with
      the cell wall hydrolase ChiB chitinase and EngA beta-1,3-glucanase on
      Saccharomyces cerevisiae, Candida albicans, Aspergillus rugulosus and A.
      fumigatus. The antifungal protein of Penicillium chrysogenum (PAF) did not
      influence the antifungal activity of ChiB or EngA, but showed antagonistic effect
      with ECB on A. nidulans, A. rugulosus and A. fumigatus. PAF had no significant
      effect on the growth of the tested yeasts as it was expected and did not
      influence significantly the antifungal activity of ECB, ChiB or EngA against
      yeasts. 

PMID- 24275597
TI  - Scaling in the correlation energies of two-dimensional artificial atoms.
AB  - We find an unexpected scaling in the correlation energy of artificial atoms,
      i.e., harmonically confined two-dimensional quantum dots. The scaling relation is
      found through extensive numerical examinations including Hartree-Fock,
      variational quantum Monte Carlo, density functional, and full configuration
      interaction calculations. We show that the correlation energy, i.e., the true
      ground-state total energy minus the Hartree-Fock total energy, follows a simple
      function of the Coulomb energy, confinement strength and number of electrons. We
      find an analytic expression for this function, as well as for the correlation
      energy per particle and for the ratio between the correlation and total energies.
      Our tests for independent diffusion Monte Carlo and coupled-cluster results for
      quantum dots-including open-shell data-confirm the generality of the scaling
      obtained. As the scaling also applies well to ?100 electrons, our results give
      interesting prospects for the development of correlation functionals within
      density functional theory. 

PMID- 24275599
TI  - Interleukin-37.
AB  - IL-37 was formerly termed IL-1 family member 7. The cytokine was discovered by in
      silico research of human databases. Although there are no genes in the databases
      with an open reading frame for a murine homologue for IL-37, human IL-37 is
      functional in the mouse. Like others members of the IL-1 family, IL-37 lacks a
      signal peptide. The precursor form of IL-37 has a caspase-1 site, but the role of
      caspase-1 in the processing and secretion of IL-37 has not been documented with
      certainty. IL-37 is similar to IL-1alpha and IL-33, in that the cytokine is found
      in the nucleus where, like IL-1alpha and IL-33, functions in transcription.
      Translocation of IL-37 to the nucleus likely involves SMAD3, which is a component
      of the TGFbeta anti-inflammatory signaling pathway. Also similar to IL-1alpha and
      IL-33, with loss of membrane integrity upon cell death, the IL-37 precursor exits
      from the cell where it binds to the IL-18 receptor alpha chain. However, this
      binding results in reduced inflammation. Without a murine form of IL-37, deletion
      studies were carried out with specific siRNA. In human monocytes deficient in IL
      37, LPS and IL-1beta induced cytokines increased 2-3 fold, suggesting that
      endogenous IL-37 serves as a break on inflammation. Indeed, in mice expressing
      human IL-37, inflammation is reduced in models of LPS shock, chemical colitis,
      cardiac ischemia and contact dermatitis. 

PMID- 24275600
TI  - Overview of the interleukin-1 family of ligands and receptors.
AB  - This issue of Seminars in Immunology on The Interleukin-1 (IL-1) Family of
      Ligands and Receptors updates the rapidly expanding importance of this family.
      There are individual chapters on IL-1alpha, IL-1beta, processing and secretion of
      IL-1beta, IL-18, IL-33, IL-36 and IL-37. In addition, a chapter of IL-1 decoy
      receptors, IL-1 signaling receptors and the clinical applications of IL-1
      blockade in human disease is included. More than any other cytokine family, the
      IL-1 family is closely linked to innate inflammatory and immune responses. This
      linkage is because the cytoplasmic segment of all members of IL-1 family of
      receptors contains a domain, which highly homologous to the cytoplasmic domains
      of all Toll like receptors (TLR). This domain is termed Toll IL-1 receptor (TIR)
      domain and mutations in the TIR of IL-1 receptors or TLR abrogates signal
      transduction. Thus, fundamental responses such as the induction of cyclo
      oxygenase type 2, increased surface expression of cellular adhesion molecules and
      increased gene expression of broad number of inflammatory molecules characterizes
      IL-1 signal transduction as it does for TLR agonists. Both TLR and IL-1 families
      non-specifically affect antigen recognition and lymphocyte function, and
      therefore act as helpers (adjuvants) for specific immune responses, now called
      acquired immunity. IL-1beta is the most studied member of the IL-1 family due to
      its role in mediating auto-inflammatory disease. Although the TLR and IL-1
      families evolved to assist host defense against infection, the IL-1 family also
      includes members that suppress inflammation, both specifically within the IL-1
      family but also non-specifically for TLR ligands and the innate immune response. 

PMID- 24275601
TI  - Interleukin-1beta in innate inflammation, autophagy and immunity.
AB  - Although IL-1beta is the master inflammatory cytokine in the IL-1 family, after
      more than ten years of continuous breeding, mice deficient in IL-1beta exhibit no
      spontaneous disease. Therefore, one concludes that IL-1beta is not needed for
      homeostasis. However, IL-1beta-deficient mice are protected against local and
      systemic inflammation due to live infections, autoimmune processes, tumor
      metastasis and even chemical carcinogenesis. Based on a large number of
      preclinical studies, blocking IL-1beta activity in humans with a broad spectrum
      of inflammatory conditions has reduced disease severity and for many, has lifted
      the burden of disease. Rare and common diseases are controlled by blocking IL
      1beta. Immunologically, IL-1beta is a natural adjuvant for responses to antigen.
      Alone, IL-1beta is not a growth factor for lymphocytes; rather in antigen
      activated immunocompetent cells, blocking IL-1 reduces IL-17 production. IL-1beta
      markedly increases in the expansion of naive and memory CD4T cells in response to
      challenge with their cognate antigen. The response occurs when only specific CD4T
      cells respond to IL-1beta and not to IL-6 or CD-28. A role for autophagy in
      production of IL-1beta has emerged with deletion of the autophagy gene ATG16L1.
      Macrophages from ATG16L1-deficient mice produce higher levels of IL-1beta after
      stimulation with TLR4 ligands via a mechanism of caspase-1 activation. The
      implications for increased IL-1beta release in persons with defective autophagy
      may have clinical importance for disease. 

PMID- 24275602
TI  - Interleukin-18, more than a Th1 cytokine.
AB  - Together with IL-12 or IL-15, interleukin-18 (IL-18) plays a major role in the
      production of interferon-gamma from T-cells and natural killer cells; thus, IL-18
      is considered to have a major role in the Th1 response. However, without IL-12,
      IL-18 is proinflammatory in an IFNgamma independent manner. IL-18 is a member of
      the IL-1 family of cytokines and similar to IL-1beta, the cytokine is synthesized
      as an inactive precursor requiring processing by caspase-1 into an active
      cytokine. IL-18 is also present as an integral membrane protein but requires
      caspase-1 for full activity in order to induce IFNgamma. Uniquely, unlike IL
      1beta, the IL-18 precursor is constitutively present in nearly all cells in
      healthy humans and animals. The activity of IL-18 is balanced by the presence of
      a high-affinity, naturally occurring IL-18 binding protein (IL-18BP). In humans,
      increased disease severity can be associated with an imbalance of IL-18 to IL
      18BP such that the levels of free IL-18 are elevated in the circulation.
      Increasing number of studies have expanded the role of IL-18 in mediating
      inflammation in animal models of disease using the IL-18BP, IL-18 deficient mice,
      neutralization of IL-18 or deficiency in the IL-18 receptor alpha chain. A role
      for IL-18 has been implicated in several autoimmune diseases, myocardial
      function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease,
      macrophage activation syndrome, sepsis and acute kidney injury, although
      paradoxically, in some models of disease, IL-18 is protective. The IL-18BP has
      been used safely in humans and clinical trials of IL-18BP as well as neutralizing
      anti-IL-18 antibodies are being tested in various diseases. 

PMID- 24275603
TI  - Modified bilobed flap for one-stage earlobe reconstruction: a case report.
AB  - Many techniques have been described in the literature for the reconstruction of
      congenital or acquired defects of the earlobe. Most techniques for earlobe
      reconstruction use adjacent tissue to compose a pedicled or bilobed flap, but
      usually require a two-stage procedure, or need a skin graft; more rarely
      reconstructive methods that led to a satisfactory result and a pleasant
      appearance in one-stage procedure have been described. We describe a personal and
      geometrical modification of the double-lobed flap according to Gavello's original
      technique, which allows to shape the anatomical curvature of the earlobe and to
      reduce the skin retraction without adding any scars or skin graft. In our
      opinion, the revisited reconstructive technique provides lots of advantages,
      improves aesthetical results and provides more natural appearance. 

PMID- 24275598
TI  - Treating inflammation by blocking interleukin-1 in humans.
AB  - IL-1 is a master cytokine of local and systemic inflammation. With the
      availability of specific IL-1 targeting therapies, a broadening list of diseases
      has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1,
      either IL-1alpha or IL-1beta, was administered to patients in order to improve
      bone marrow function or increase host immune responses to cancer, these patients
      experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias,
      fatigue, gastrointestinal upset and sleep disturbances; frank hypotension
      occurred. Thus it was not unexpected that specific pharmacological blockade of IL
      1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL
      1 activity in a broad spectrum of inflammatory syndromes results in a rapid and
      sustained reduction in disease severity. In common conditions such as heart
      failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL
      1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the
      IL-1 receptor and therefore reduces the activity of IL-1alpha and IL-1beta. A
      soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti
      interleukin-1beta antibody, canakinumab, are also approved. A monoclonal antibody
      directed against the IL-1 receptor and a neutralizing anti-IL-1alpha are in
      clinical trials. By specifically blocking IL-1, we have learned a great deal
      about the role of this cytokine in inflammation but equally important, reducing
      IL-1 activity has lifted the burden of disease for many patients. 

PMID- 24275604
TI  - Application of depression rating scales in patients with Parkinson's disease with
      and without co-Occurring anxiety.
AB  - BACKGROUND: In patients with Parkinson's disease (PD), depressive symptom rating
      scales facilitate identification of depressive disorders, which are common and
      disabling. Anxiety disturbances in PD, which lack valid assessment scales,
      frequently co-occur with PD-depression, are under-recognized, and require
      different interventions than depressive disorders. Whether high anxiety rates in
      PD confound depression scale performance or if any depression scales also predict
      anxiety disturbances is not known. OBJECTIVE: To test the impact of co-occurring
      anxiety disorders on psychometric properties of depression rating scales in
      depressed PD patients and compare disability between PD patients with anxiety,
      depression, and comorbid anxiety and depressive disorders. METHODS: PD subjects
      (n = 229) completed self-report and clinician-administered depression scales.
      Receiver operating characteristic curves were developed to estimate psychometric
      properties of each scale in those with depression alone, anxiety alone, and
      comorbid depression and anxiety. Between-group differences on all measures were
      examined. RESULTS: Comorbid anxiety did not affect the psychometric properties of
      any scale when identifying depressive disorders, but is associated with greater
      symptom severity and disability. Depression-scale scores were not significantly
      different between subjects with anxiety disorders only and those without
      depressive or anxiety diagnoses. CONCLUSIONS: Co-occurring anxiety disorders do
      not impact performance of depression rating scales in depressed PD patients.
      However, depression rating scales do not adequately identify anxiety disturbances
      alone or in patients with depression.

PMID- 24275606
TI  - Formulation of abalone hemocyanin with high antiviral activity and stability.
AB  - Hemocyanin has been shown to have potential antiviral activity against herpes
      simplex virus type-1. However, current liquid formulations have short shelf life
      and high risk of bacterial contamination. The aim of our study was to develop a
      stable functional formulation. Analytical techniques (nano-differential scanning
      calorimetry and spectroscopy) and biological assays (cytotoxicity and plaque
      reduction) were employed to measure the effect of sugar addition on the physical
      properties and shelf life of the solid formulated hemocyanin. Sucrose improved
      thermal stability significantly by both increasing the aggregation onset
      temperature (70 degrees C to>78  degrees C) and enhancing the activation energy
      (18%). Lyophilisation without trehalose caused degradation and unfolding of the
      alpha-helices of hemocyanin. However, the addition of an optimal proportion of
      trehalose:protein (5:1 by weight) prevented the degradation and unfolding during
      lyophilisation, hence maintained the protein solubility. The estimated ED50
      values of the formulated solid (0.43+/-0.1) and liquid samples (0.37+/-0.06) were
      similar in magnitude, and were significantly lower than the respective controls;
      thus, confirming enhanced antiviral activity of the formulation. Formulated
      compounds were stable for six months at 5  degrees C storage. The enhanced shelf
      life and stable antiviral activity of the formulation offers its significant
      potential as effective therapeutic agent in future clinical applications.

PMID- 24275607
TI  - Inhibition of fatty acid amide hydrolase (FAAH) as a novel therapeutic strategy
      in the treatment of pain and inflammatory diseases in the gastrointestinal tract.
AB  - Fatty acid amide hydrolase (FAAH) is the enzyme crucially involved in the
      modulation of physiological processes mediated by anandamide (AEA), as well as
      other endocannabinoids and non-cannabinoid biolipids in the gastrointestinal (GI)
      tract. FAAH also plays a major role in the etiology and the course of GI diseases
      and the inhibition of the enzyme has recently become a potential target for their
      therapy. In this review we look at the pharmacology of FAAH and possible clinical
      application of FAAH inhibitors in the treatment of GI disorders. In particular,
      we focus on inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS),
      whose symptoms include abdominal pain and motility disturbances. We also discuss
      why the inhibitor-based drugs may replace in future conventional therapies for
      IBD and IBS. 

PMID- 24275608
TI  - Environmentally relevant bouts of cooling stimulate corticosterone secretion in
      free-living eastern bluebird (Sialia sialis) nestlings: potential links between
      maternal behavior and corticosterone exposure in offspring.
AB  - In vertebrates, exposure to stressful stimuli or to elevated glucocorticoids
      early in development can contribute to phenotypic variation that may have
      significant fitness consequences. In species with altricial young, offspring may
      be partially buffered from elevations in glucocorticoids by a period of low
      glucocorticoid responsiveness to stressors coupled with high levels of parental
      care. Because altricial young depend heavily on their parents for warmth,
      parental brooding behavior could buffer offspring from glucocorticoid exposure
      associated with cooling. We studied eastern bluebirds (Sialia sialis) with two
      goals: (1) to determine whether an experimental drop in body temperature such as
      that which might occur when a brooding female is off the nest was sufficient to
      stimulate glucocorticoid secretion in young chicks, and (2) to examine the extent
      to which chicks experienced such bouts of cooling in the field. We subjected
      chicks to treatments simulating nest temperatures while females were brooding or
      absent from the nest. We also recorded chick surface temperatures and ambient
      temperatures at nests during the first week of the brood period. Reductions of
      surface temperature of less than 10 degrees C significantly elevated
      corticosterone secretion in chicks as young as 5days old, and thermal and
      hormonal responses of chicks to cooling increased in an age-dependent manner. One
      quarter of broods experienced repeated, natural bouts of cooling of this
      magnitude or greater in the nest. Our data suggest that natural variations in
      maternal brooding patterns can result in differential exposure of offspring to
      glucocorticoids, and this may have important phenotypic consequences later in
      life. 

PMID- 24275609
TI  - Linking social environment and stress physiology in feral mares (Equus caballus):
      group transfers elevate fecal cortisol levels.
AB  - Feral horses (Equus caballus) have a complex social structure, the stability of
      which is important to their overall health. Behavioral and demographic research
      has shown that decreases in group (or band) stability reduce female fitness, but
      the potential effects on the physiological stress response have not been
      demonstrated. To fully understand how band stability affects group-member
      fitness, we need to understand not only behavioral and demographic, but also
      physiological consequences of decreases to that stability. We studied group
      changes in feral mares (an activity that induces instability, including both male
      and female aggression) on Shackleford Banks, NC. We found that mares in the midst
      of changing groups exhibit increased fecal cortisol levels. In addition, mares
      making more group transfers show higher levels of cortisol two weeks post
      behavior. These results offer insights into how social instability is integrated
      into an animal's physiological phenotype. In addition, our results have important
      implications for feral horse management. On Shackleford Banks, mares contracepted
      with porcine zona pellucida (PZP) make approximately 10 times as many group
      changes as do untreated mares. Such animals may therefore be at higher risk of
      chronic stress. These results support the growing consensus that links between
      behavior and physiological stress must be taken into account when managing for
      healthy, functional populations. 

PMID- 24275605
TI  - The role of innate and adaptive immunity in Parkinson's disease.
AB  - In recent years, inflammation has become implicated as a major pathogenic factor
      in the onset and progression of Parkinson's disease. Understanding the precise
      role for inflammation in PD will likely lead to understanding of how sporadic
      disease arises. In vivo evidence for inflammation in PD includes microglial
      activation, increased expression of inflammatory genes in the periphery and in
      the central nervous system (CNS), infiltration of peripheral immune cells into
      the CNS, and altered composition and phenotype of peripheral immune cells. These
      findings are recapitulated in various animal models of PD and are reviewed
      herein. Furthermore, we examine the potential relevance of PD-linked genetic
      mutations to altered immune function and the extent to which environmental
      exposures that recapitulate these phenotypes, which may lead to sporadic PD
      through similar mechanisms. Given the implications of immune system involvement
      on disease progression, we conclude by reviewing the evidence supporting the
      potential efficacy of immunomodulatory therapies in PD prevention or treatment.
      There is a clear need for additional research to clarify the role of immunity and
      inflammation in this chronic, neurodegenerative disease. 

PMID- 24275610
TI  - Trends in plant virus epidemiology: opportunities from new or improved
      technologies.
AB  - This review focuses on new or improved technologies currently being applied, or
      likely to be applied in the future, to worldwide research on plant virus
      epidemiology. Recent technological advances and innovations provide many
      opportunities to improve understanding of the way diverse types of plant virus
      epidemics develop and how to manage them. The review starts at the macro level by
      considering how recent innovations in remote sensing and precision agriculture
      can provide valuable information about (i) virus epidemics occurring at
      continental, regional or district scales (via satellites) and within individual
      crops (mostly via lightweight unmanned aerial vehicles), and (ii) exactly where
      to target control measures. It then considers recent improvements in information
      systems and innovations in modelling that improve (i) understanding of virus
      epidemics and ability to predict them, and (ii) delivery to end-users of critical
      advice on control measures, such as Internet-based Decision Support Systems. The
      review goes on to discuss how advances in analysis of spatiotemporal virus spread
      patterns within crops can help to enhance understanding of how virus epidemics
      develop and validate potentially useful virus control measures. At the micro
      level, the review then considers the many insights that advances in molecular
      epidemiology can provide about genetic variation within plant virus populations
      involved in epidemics, and how this variation drives what occurs at the macro
      level. Next, it describes how recent innovations in virus detection technologies
      are providing many opportunities to collect and analyse new types, and ever
      increasing amounts, of data about virus epidemics, and the genetic variability of
      the virus populations involved. Finally, the implications for plant virus
      epidemiology of technologies likely to be important in the future are considered.
      To address looming world food insecurity and threats to plant biodiversity
      resulting from climate change and rapid population growth, it is important that
      new and improved technologies that help understand and control epidemics of
      damaging plant viruses are adopted as smoothly and speedily as possible. 

PMID- 24275611
TI  - Unruptured intracranial aneurysms conservatively followed with serial CT
      angiography: could morphology and growth predict rupture?
AB  - BACKGROUND AND PURPOSE: Despite several landmark studies, the natural history of
      unruptured intracranial aneurysms (UIA) remains uncertain. Our aim was to
      identify or confirm factors predictive of rupture of UIA being observed
      conservatively with serial CT angiography (CTA) in a North American patient
      population. METHODS: We performed a retrospective review of patients with UIA
      being followed with serial CTA studies from 1999 to 2010. The following features
      for each aneurysm were cataloged from the official radiologic reports and CTA
      images: maximum diameter, growth between follow-up studies, location,
      multiplicity, wall calcification, intraluminal thrombus and morphology.
      Univariate logistic regression analysis of the potential independent risk factors
      for aneurysm rupture was performed. Statistically significant risk factors from
      the univariate analysis were then entered into a multivariate logistic regression
      analysis. RESULTS: 152 patients with a total of 180 UIA had at least two CTA
      studies. Six aneurysms in six different patients ruptured during the CTA follow
      up period for an overall rupture rate of 3.3% and an annual rupture rate of
      0.97%. All ruptured aneurysms were >=9 mm. In the univariate analysis, the
      statistically significant predictors of aneurysm rupture were aneurysm size
      (p=0.003), aneurysm growth (p<0.0001) and aneurysm multilobulation (p=0.001). The
      risk factors that remained significant following the multivariate analysis were
      growth (OR 55.9; 95% CI 4.47 to 700.08; p=0.002) and multilobulation (OR 17.4;
      95% CI 1.52 to 198.4; p=0.022). CONCLUSIONS: Aneurysm morphology and interval
      growth are characteristics predictive of a higher risk of subsequent rupture
      during conservative CTA follow-up.

PMID- 24275612
TI  - Individualised but not general alcohol Stroop predicts alcohol use.
AB  - BACKGROUND: Recently, there have been investigations that have targeted improving
      the relatively poor validity and reliability of attentional bias measures. These
      studies have demonstrated that individuals show elevated attentional bias to
      stimuli associated with their drinking history, although to date, the predictive
      utility of these measures has yet to be assessed. The current study aimed to
      investigate the predictive value of an individualised alcohol Stroop task
      compared to that of an alcohol Stroop task with general alcohol-related words in
      a sample of non-dependent undergraduate drinkers. METHOD: 48 undergraduate social
      drinkers completed questionnaire measures of alcohol consumption and hazardous
      drinking which were combined to get an alcohol involvement measure. Participants
      also completed three blocked format Stroop tasks, a control Stroop (containing
      soft drink-related words), a general alcohol Stroop (containing a mixture of
      alcohol-related words) and an individualised Stroop that contained words relating
      to the participants' favourite alcoholic drink. RESULTS: Although there was no
      significant difference in participants' performance across the three different
      Stroop tasks, only performance on the individualised Stroop was associated with
      alcohol involvement. Notably, the individualised Stroop predicted variance in
      drinking after controlling for demographics and general alcohol Stroop
      performance. CONCLUSIONS: This study indicates that adopting individualised
      stimuli into attentional bias tasks may increase their predictive validity.

PMID- 24275613
TI  - Structure and polymer dynamics within PNIPAM-based microgel particles.
AB  - The synthesis of temperature-responsive microgels of poly(N-isopropylacrylamide)
      (PNIPAM) was first reported in 1986 and, since then, there have been hundreds of
      publications describing the preparation, characterization and applications of
      these systems. This paper reviews the developments concerning the study of the
      structure of PNIPAM-based microgels performed over the last years using small
      angle neutron scattering (SANS) and also the investigations of the polymer-chain
      dynamics within the microgels carried out with incoherent elastic and
      quasielastic neutron scattering, and pulse field gradient nuclear magnetic
      resonance (PFG-NMR) techniques. Furthermore, the self-diffusion coefficient of
      the water molecules within the microgel, determined by means of solvent
      relaxation NMR, is also discussed as a function of the polymer volume fraction of
      the microgels. 

PMID- 24275614
TI  - Chromatin and DNA sequences in defining promoters for transcription initiation.
AB  - One of the key events in eukaryotic gene regulation and consequent transcription
      is the assembly of general transcription factors and RNA polymerase II into a
      functional pre-initiation complex at core promoters. An emerging view of
      complexity arising from a variety of promoter associated DNA motifs, their
      binding factors and recent discoveries in characterising promoter associated
      chromatin properties brings an old question back into the limelight: how is a
      promoter defined? In addition to position-dependent DNA sequence motifs,
      accumulating evidence suggests that several parallel acting mechanisms are
      involved in orchestrating a pattern marked by the state of chromatin and general
      transcription factor binding in preparation for defining transcription start
      sites. In this review we attempt to summarise these promoter features and discuss
      the available evidence pointing at their interactions in defining transcription
      initiation in developmental contexts. This article is part of a Special Issue
      entitled: Chromatin and epigenetic regulation of animal development. 

PMID- 24275616
TI  - Influence of implant rod curvature on sagittal correction of scoliosis deformity.
AB  - BACKGROUND CONTEXT: Deformation of in vivo-implanted rods could alter the
      scoliosis sagittal correction. To our knowledge, no previous authors have
      investigated the influence of implanted-rod deformation on the sagittal deformity
      correction during scoliosis surgery. PURPOSE: To analyze the changes of the
      implant rod's angle of curvature during surgery and establish its influence on
      sagittal correction of scoliosis deformity. STUDY DESIGN: A retrospective
      analysis of the preoperative and postoperative implant rod geometry and angle of
      curvature was conducted. PATIENT SAMPLE: Twenty adolescent idiopathic scoliosis
      patients underwent surgery. Average age at the time of operation was 14 years.
      OUTCOME MEASURES: The preoperative and postoperative implant rod angle of
      curvature expressed in degrees was obtained for each patient. METHODS: Two
      implant rods were attached to the concave and convex side of the spinal
      deformity. The preoperative implant rod geometry was measured before surgical
      implantation. The postoperative implant rod geometry after surgery was measured
      by computed tomography. The implant rod angle of curvature at the sagittal plane
      was obtained from the implant rod geometry. The angle of curvature between the
      implant rod extreme ends was measured before implantation and after surgery. The
      sagittal curvature between the corresponding spinal levels of healthy adolescents
      obtained by previous studies was compared with the implant rod angle of curvature
      to evaluate the sagittal curve correction. The difference between the
      postoperative implant rod angle of curvature and normal spine sagittal curvature
      of the corresponding instrumented level was used to evaluate over or under
      correction of the sagittal deformity. RESULTS: The implant rods at the concave
      side of deformity of all patients were significantly deformed after surgery. The
      average degree of rod deformation Deltatheta at the concave and convex sides was
      15.8 degrees  and 1.6 degrees , respectively. The average preoperative and
      postoperative implant rod angle of curvature at the concave side was 33.6 degrees
      and 17.8 degrees , respectively. The average preoperative and postoperative
      implant rod angle of curvature at the convex side was 25.5 degrees  and 23.9
      degrees , respectively. A significant relationship was found between the degree
      of rod deformation and preoperative implant rod angle of curvature (r=0.60,
      p<.005). The implant rods at the convex side of all patients did not have
      significant deformation. The results indicate that the postoperative sagittal
      outcome could be predicted from the initial rod shape. CONCLUSIONS: Changes in
      implant rod angle of curvature may lead to over- or undercorrection of the
      sagittal curve. Rod deformation at the concave side suggests that corrective
      forces acting on that side are greater than the convex side.

PMID- 24275615
TI  - The Spine Instability Neoplastic Score: an independent reliability and
      reproducibility analysis.
AB  - BACKGROUND: Metastatic vertebral instability has not yet been clearly defined in
      the literature; there still exists a paucity of reliable criteria to assess the
      risk of vertebral collapse. PURPOSE: We performed an independent interobserver
      and intraobserver agreement evaluation of the Spine Instability Neoplastic Score
      (SINS) and correlated the score with selected clinical cases and the treatment
      they received. STUDY DESIGN: Independent reliability study for the newly created
      SINS. PATIENT SAMPLE: Thirty patients who underwent either radiotherapy alone or
      surgery followed by radiotherapy were randomly selected from the orthopedic
      surgery and radiotherapy department's databases. OUTCOME MEASURES: Patients were
      rated and classified for spinal stability using SINS. Intraclass correlation
      coefficient (ICC) and Fleiss's kappa measures were occupied for reliability
      analysis. METHODS: Patients who underwent either radiotherapy alone or surgery
      followed by radiotherapy were randomly selected and classified for spinal
      stability using the SINS by orthopedic surgeons and nonorthopedic oncology
      specialists. ICC and Fleiss's kappa were calculated for inter- and intraobserver
      agreement. A comparative analysis of SINS and the actual management was also
      conducted. RESULTS: Interobserver ICC reliability for the SINS was 0.79; kappa
      values for location, pain, bone quality, alignment, vertebral body collapse, and
      posterolateral involvement were 0.81, 0.58, 0.21, 0.45, 0.42, and 0.29
      respectively. Intraobserver ICC for the SINS scores was 0.96; ICC values for the
      same components were 0.98, 0.98, 0.87, 0.88, 0.92, and 0.86, respectively.
      Potentially unstable lesions (SINS score>=7) were operated on in 62.5%.
      CONCLUSIONS: SINS seem to be a reproducible tool that could be used equally by
      multiple specialists to estimate metastatic vertebral stability; however,
      prospective clinical validation is still pending.

PMID- 24275617
TI  - Evaluation of a bipolar-cooled radiofrequency device for ablation of bone
      metastases: preclinical assessment in porcine vertebrae.
AB  - BACKGROUND CONTEXT: Cancer spread to the spine affects bone stability and can
      lead to pathologic fracture and neurologic impairment. Radiofrequency ablation
      (RFA) recently has gained popularity in treating skeletal tumors. Conventional
      RFA devices use a monopolar design, which limits the ability to comprehensively
      treat large tumors in bony tissues and may pose risks to adjacent critical normal
      neurologic tissues when applied to vertebrae. New bipolar-cooled radiofrequency
      (BCRF) may generate larger controlled lesions without the same degree of risk to
      adjacent structures. PURPOSE: The purpose of this study was to evaluate the
      feasibility, efficacy, and safety of RFA with the use of a new bone-specific,
      BCRF probe in a porcine vertebral model and to evaluate the ability of magnetic
      resonance (MR) imaging to represent histologic outcomes of RFA treatment. STUDY
      DESIGN: Basic science: preclinical in vivo study. METHODS: RFA was evaluated in
      three noncontiguous lumbar vertebrae in six Yorkshire pigs (25-30 kg). Via a
      transpedicular approach for probe placement, two vertebrae received BCRF
      treatment and one vertebrae served as a sham control. MR imaging and neurological
      assessments were conducted pre- and posttreatment as well as immediately before
      animal sacrifice (n=3 at day 0, n=3 at day 14). MR ablation zones were compared
      with hematoxylin and eosin-stained histological sections. RESULTS: With BCRF,
      large reproducible zones of ablation were achieved, confined within the
      vertebrae, without damage to adjacent tissues or the spinal cord. All animals
      demonstrated normal consistent neurologic behavior pre- and posttreatment.
      External tissue temperatures around targeted vertebrae were not increased. MR
      imaging after 14 days was more effective in demonstrating ablation effects than
      images on day 0, with radiologic findings most apparent on T2-weighted sequences.
      Histologic analysis of samples corresponded well to the zones of ablation
      observed on MR images (R=0.9, p<.01). CONCLUSIONS: The study demonstrated
      feasibility, safety, and effectiveness of BCRF ablation of vertebral bone. This
      motivates ongoing preclinical evaluation in diseased models to further explore
      the potential for its use in clinical treatment of metastatic vertebrae.

PMID- 24275618
TI  - Update on endocrine and metabolic therapy-related late effects observed in
      survivors of childhood neoplasia.
AB  - PURPOSE OF REVIEW: To provide a summary of the most recent research pertaining to
      the endocrine and metabolic complications observed in childhood cancer survivors.
      RECENT FINDINGS: Data on prevalence and risk associations are increasingly
      available from large cohorts of childhood cancer survivors. New directions in
      research include novel risk-prediction strategies and the study of genetic
      predisposition. SUMMARY: Endocrine complications are observed in more than 50% of
      adult childhood cancer survivors. Some continue to develop decades following
      cancer treatment exposures. The present review provides a summary of the most
      recent outcomes research pertaining to growth, thyroid, gonadal-reproductive,
      bone and body composition with emphasis on new directions and challenges in each
      area.

PMID- 24275619
TI  - Changing perspectives in screening for congenital hypothyroidism and congenital
      adrenal hyperplasia.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent information
      that has had a significant impact on the laboratory diagnosis and clinical
      management of newborns with congenital hypothyroidism and congenital adrenal
      hyperplasia (CAH). RECENT FINDINGS: An approximate doubling of the incidence rate
      of congenital hypothyroidism in many parts of the world has been attributed to
      increased detection of infants with mild disease, delayed thyroid stimulating
      hormone elevations and demographic changes. A substantial number of children with
      modest thyroid stimulating hormone elevations on screening have permanent
      disease. Circulating levels of thyroxine may vary among hypothyroid children who
      are given identical dosages of medication. Treated infants should be monitored
      every 1-2 months during the first year of life. Although, generic and brand name
      thyroxine preparations may not be bioequivalent, children can be well controlled
      on generic formulations.Enzyme linked immunoassay assay for 17
      hydroxyprogesterone is associated with a high rate of false positive specimens.
      In attempts to minimize this problem, some programs have resorted to two-tier
      screening of the initial specimen with steroid profiling as the second tier.
      Several programs are routinely testing second specimens in an effort to reduce
      the incidence of missed CAH cases. SUMMARY: This review explains the uptick in
      incidence rate of congenital hypothyroidism and underscores issues in management
      that can affect developmental outcome. One specimen two-tier testing for CAH
      resulted in an increased false negative rate without significantly reducing the
      false positive rate. The benefit of collecting second specimens for CAH screening
      is problematic. Optimal treatment of CAH continues to pose a challenge.

PMID- 24275620
TI  - Update on neonatal hypoglycemia.
AB  - PURPOSE OF REVIEW: Neonatal hypoglycemia is one of the most common biochemical
      abnormalities encountered in the newborn. However, controversy remains
      surrounding its definition and management especially in asymptomatic patients.
      RECENT FINDINGS: New information has been published that describes the incidence
      and timing of low glucose concentrations in the groups most at risk for
      asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study
      failed to find an association between repetitive low glucose concentrations and
      poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to
      hyperinsulinism, especially genetic causes, continued to be associated with brain
      injury. New advances were made in the diagnosis and management of
      hyperinsulinism, including acquired hyperinsulinism in small for gestational age
      infants and others. Continuous glucose monitoring remains an attractive strategy
      for future research in this area. SUMMARY: The fundamental question of how best
      to manage asymptomatic newborns with low glucose concentrations remains
      unanswered. Balancing the risks of overtreating newborns with low glucose
      concentrations who are undergoing a normal transition following birth against the
      risks of undertreating those in whom low glucose concentrations are pathological,
      dangerous, and/or a harbinger of serious metabolic disease remains a challenge.

PMID- 24275622
TI  - Treatment patterns, healthcare resource utilization and costs in patients with
      bipolar disorder, newly treated with extended release or immediate release
      quetiapine fumarate using US healthcare administrative claims data.
AB  - BACKGROUND: Differences in treatment patterns, health care resource use, and
      costs are expected among patients newly treated with quetiapine extended release
      (XR) or quetiapine immediate release (IR). OBJECTIVE: To compare treatment
      patterns, health care resource use, and costs in patients with bipolar disorder
      newly treated with quetiapine XR or quetiapine IR. METHODS: This was an
      observational, retrospective cohort study that used HealthCore Integrated
      Research Database-identified patients (age range, 18-64 years) with an
      International Classification of Disease, Ninth Revision diagnosis of bipolar
      disorder and >=1 pharmacy claim for quetiapine XR or quetiapine IR between
      October 2, 2008, and July 31, 2010. Outcomes were as follows: patient
      characteristics at the index date (first claim for quetiapine XR or quetiapine
      IR); 12-month preindex clinical characteristics, health care resource use, and
      costs; and 12-month postindex treatment patterns, health care resource use, and
      costs, assessed using generalized linear models (adjusted for index date and
      preindex patient demographic characteristics, clinical characteristics, health
      care resource use, and costs). RESULTS: In total, 3049 patients with bipolar
      disorder were analyzed (651 in the quetiapine XR group and 2398 in the quetiapine
      IR group). Of patients initiating treatment with quetiapine XR, 8.8% had no
      change in or discontinuation of their index therapy compared with 5.7% of
      patients treated with quetiapine IR (adjusted odds ratio, 1.44; 95% confidence
      interval, 1.03-2.00; P = 0.0317). The average daily dose (adjusted mean) of
      quetiapine XR was higher than quetiapine IR (225 vs 175 mg/d, P < 0.0001). An
      average daily dose of 300 to 800 mg was reached sooner (15.6 vs 30.8 days, P =
      0.0049) and in more patients (44.2% vs 27.2%, P < 0.0001) who were taking
      quetiapine XR compared with patients taking quetiapine IR. No differences in
      total health care costs were found between the cohorts; however, patients taking
      quetiapine XR were less likely to be hospitalized for mental health-related
      reasons (12.1% vs 18.3%, P = 0.0022) and incurred lower mental health-related
      costs (US $6686 vs US $7577, P = 0.0063) compared with patients taking quetiapine
      IR. CONCLUSIONS: Treatment patterns and dosing differ in patients with bipolar
      disorder treated with quetiapine XR compared with those treated with quetiapine
      IR. Mental health-related hospitalizations and costs may be reduced in the 12
      months after patients initiating treatment with quetiapine XR compared with
      initiating treatment with quetiapine IR.

PMID- 24275621
TI  - Endocrinology of anorexia nervosa in young people: recent insights.
AB  - PURPOSE OF REVIEW: Anorexia nervosa is among the most prevalent chronic medical
      conditions in young adults. It has acute as well as long-term consequences, some
      of which, such as low bone mineral density (BMD), are not completely reversible
      even after weight restoration. This review discusses our current understanding of
      endocrine consequences of anorexia nervosa. RECENT FINDINGS: Anorexia nervosa is
      characterized by changes in multiple neuroendocrine axes including acquired
      hypogonadotropic hypogonadism, growth hormone resistance with low insulin-like
      growth factor-1 (likely mediated by fibroblast growth factor-1), relative
      hypercortisolemia, alterations in adipokines such as leptin, adiponectin and
      resistin, and gut peptides including ghrelin, PYY and amylin. These changes in
      turn contribute to low BMD. Studies in anorexia nervosa have demonstrated
      abnormalities in bone microarchitecture and strength, and an association between
      increased marrow fat and decreased BMD. One study in adolescents reported an
      improvement in BMD following physiologic estrogen replacement, and another in
      adults demonstrated improved BMD following risedronate administration. Brown
      adipose tissue is reduced in anorexia nervosa, consistent with an adaptive
      response to the energy deficit state. SUMMARY: Anorexia nervosa is associated
      with widespread physiologic adaptations to the underlying state of
      undernutrition. Hormonal changes in anorexia nervosa affect BMD adversely.
      Further investigation is underway to optimize therapeutic strategies for low BMD.

PMID- 24275625
TI  - Evaluating the effect of splitting cylindrical power on improving patient
      tolerance to toric lens misalignment.
AB  - PURPOSE: Evaluating the impact of splitting toric power on patient tolerance to
      misorientation such as with intraocular lens rotation. SETTING: University vision
      clinic. METHODS: Healthy, non astigmats had +1.50D astigmatism induced with
      spectacle lenses at 90 degrees , 135 degrees , 180 degrees  and +3.00D at 90
      degrees . Two correcting cylindrical lenses of the opposite sign and half the
      power each were subsequently added to the trial frame misaligned by 0 degrees , 5
      degrees  or 10 degrees  in a random order and misorientated from the initial axis
      in a clockwise direction by up to 15 degrees  in 5 degrees  steps. A second group
      of adapted astigmats with between 1.00 and 3.00DC had their astigmatism corrected
      with two toric spectacle lenses of half the power separated by 0 degrees , 5
      degrees  or 10 degrees  and misorientated from the initial axis in both
      directions by up to 15 degrees  in 5 degrees  steps. Distance, high contrast
      visual acuity was measured using a computerised test chart at each lens
      misalignment and misorientation. RESULTS: Misorientation of the split toric
      lenses caused a statistically significant drop in visual acuity (F=70.341;
      p<0.001). Comparatively better acuities were observed around 180 degrees , as
      anticipated (F=3.775; p=0.035). Misaligning the split toric power produced no
      benefit in visual acuity retention with axis misorientation when subjects had
      astigmatism induced with a low (F=2.190, p=0.129) or high cylinder (F=0.491,
      p=0.617) or in the adapted astigmats (F=0.120, p=0.887). CONCLUSION: Misalignment
      of toric lens power split across the front and back lens surfaces had no
      beneficial effect on distance visual acuity, but also no negative effect.

PMID- 24275626
TI  - Growing impact of restenosis on the surgical treatment of peripheral arterial
      disease.
AB  - BACKGROUND: Patients with peripheral arterial disease often experience treatment
      failure from restenosis at the site of a prior peripheral endovascular
      intervention (PVI) or lower extremity bypass (LEB). The impact of these treatment
      failures on the utilization and outcomes of secondary interventions is poorly
      understood. METHODS AND RESULTS: In our regional vascular quality improvement
      collaborative, we compared 2350 patients undergoing primary infrainguinal LEB
      with 1154 patients undergoing secondary infrainguinal LEB (LEB performed after
      previous revascularization in the index limb) between 2003 and 2011. The
      proportion of patients undergoing secondary LEB increased by 72% during the study
      period (22% of all LEBs in 2003 to 38% in 2011, P<0.001). In-hospital outcomes,
      such as myocardial infarction, death, and amputation, were similar between
      primary and secondary LEB groups. However, in both crude and propensity-weighted
      analyses, secondary LEB was associated with significantly inferior 1-year
      outcomes, including major adverse limb event-free survival (composite of death,
      new bypass graft, surgical bypass graft revision, thrombectomy/thrombolysis, or
      above-ankle amputation; Secondary LEB MALE-free survival = 61.6% vs primary LEB
      MALE-free survival = 67.5%, P=0.002) and reintervention or amputation-free
      survival (composite of death, reintervention, or above-ankle amputation;
      Secondary LEB RAO-free survival = 58.9% vs Primary LEB RAO-free survival 64.1%,
      P=0.003). Inferior outcomes for secondary LEB were observed regardless of the
      prior failed treatment type (PVI or LEB). CONCLUSIONS: In an era of increasing
      utilization of PVI, a growing proportion of patients undergo LEB in the setting
      of a prior failed PVI or surgical bypass. When caring for patients with
      peripheral arterial disease, physicians should recognize that first treatment
      failure (PVI or LEB) affects the success of subsequent revascularizations.

PMID- 24275627
TI  - Pulmonary embolism in ischemic stroke: clinical presentation, risk factors, and
      outcome.
AB  - BACKGROUND: Limited information is available on the frequency of pulmonary
      embolism (PE) in patients with an acute ischemic stroke (AIS). We evaluated
      clinical characteristics, predisposing factors, and outcomes in AIS patients with
      PE. METHODS AND RESULTS: We included all AIS patients admitted to participating
      institutions in the Registry of the Canadian Stroke Network. Clinically PE was
      documented by a physician and confirmed by computed tomography pulmonary
      angiography within 30 days of the stroke case index. The primary outcome was
      death or disability at discharge. Secondary outcomes included disposition, length
      of hospital stay, mortality at 3 months and 1 year. Among 11 287 patients with
      AIS, PE was found in 89 (0.78%) patients. History of cancer, deep vein thrombosis
      (DVT)/PE, and DVT during the hospitalization were associated with PE. PE was
      associated with higher risk of death at 30 days (25.8% versus 13.6%; P<0.001), at
      1 year (47.2% versus 24.6%; P<0.001), and disability at discharge (85.4% versus
      63.6%; P<0.001). Mean length of stay was longer in stroke patients with PE (36
      versus 16 days; P=0.001). After adjusting for age, sex, and stroke severity, PE
      remained associated with lower survival at 30 days and 1 year, and death or
      disability at discharge (OR 3.02; 95% CI 1.56 to 5.83). CONCLUSIONS: In this
      large cohort study, PE occurred in nearly 1% of AIS patients. PE was more common
      in patients with severe stroke, history of cancer, previous DVT/PE or acute DVT
      and associated with lower short- and long-term survival, greater disability, and
      longer length of stay.

PMID- 24275628
TI  - Effect of sleep apnea and continuous positive airway pressure on cardiac
      structure and recurrence of atrial fibrillation.
AB  - BACKGROUND: Sleep apnea (SA) is associated with an increased risk of atrial
      fibrillation (AF). We sought to determine the effect of SA on cardiac structure
      in patients with AF, whether therapy for SA was associated with beneficial
      cardiac structural remodelling, and whether beneficial cardiac structural
      remodelling translated into a reduced risk of recurrence of AF after pulmonary
      venous isolation (PVI). METHODS AND RESULTS: A consecutive group of 720 patients
      underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142,
      20%) were more likely to be male, diabetic, and hypertensive and have an
      increased pulmonary artery pressure, right ventricular volume, atrial dimensions,
      and left ventricular mass. Treated SA was defined as duration of continuous
      positive airway pressure therapy of >4 hours per night. Treated SA patients
      (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower
      ventricular mass, and smaller left atrium. During a follow-up of 42 months, AF
      recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in
      patients with SA, 30% in patients without SA, 68% in patients with untreated SA,
      and 35% in patients with treated SA. In a multivariable model, the presence of SA
      (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio
      1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence.
      CONCLUSIONS: Patients with SA have an increased blood pressure, pulmonary artery
      pressure, right ventricular volume, left atrial size, and left ventricular mass.
      Therapy with continuous positive airway pressure is associated with lower blood
      pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence
      after PVI.

PMID- 24275629
TI  - Peripheral endothelial function and cardiovascular events in high-risk patients.
AB  - BACKGROUND: Endothelial dysfunction is a key component of vascular vulnerability.
      Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry,
      can noninvasively evaluate endothelial function. This study was designed to
      determine the additional prognostic value of endothelial function to the Synergy
      Between PCI With Taxus and Cardiac Surgery Score (SYNTAXsc) and the Framingham
      Risk Score (FRS) in predicting cardiovascular events in high-risk patients.
      METHODS AND RESULTS: We undertook a two-center prospective study in 528 stable
      patients at high-risk for cardiovascular events from the years 2006-2011. The RHI
      was measured before coronary angiography and coronary complexity was assessed by
      SYNTAXsc. After optimal therapies including coronary revascularization, there was
      follow-up with patients until August 2012. Cardiovascular events consist of
      cardiovascular death, myocardial infarction, unstable angina, ischemic stroke,
      coronary revascularization, heart failure-induced hospitalization, aortic
      disease, and peripheral arterial disease. During 1468 person-years of follow-up,
      105 patients developed cardiovascular events. Multivariate Cox proportional
      hazards analysis identified B-type natriuretic peptide (BNP), SYNTAXsc, and RHI
      as independent cardiovascular event predictors (hazard ratio [95% confidence
      interval]: natural logarithm of BNP per 0.1: 1.019 [1.002 to 1.037]; P=0.023,
      SYNTAXsc per tertile: 2.426 [1.825 to 3.225]; P<0.0001, RHI per 0.1: 0.761 [0.673
      to 0.859]; P<0.0001). When RHI was added to the FRS, BNP, and SYNTAXsc, net
      reclassification index was significantly improved (27.5%; P<0.0001), with a
      significant increase in the C-statistic (from 0.728 [0.679 to 0.778] to 0.766
      [0.726 to 0.806]; P=0.031). CONCLUSIONS: Advanced endothelial dysfunction
      significantly correlated with near future cardiovascular events in high-risk
      patients. This physiological vascular measurement improved risk discrimination
      when added to the FRS, BNP, and SYNTAXsc. CLINICAL TRIAL REGISTRATION URL:
      clinicaltrials.gov (http://www.clinicaltrials.gov). Unique identifier:
      NCT00737945.

PMID- 24275631
TI  - Impact of atrial fibrillation on stroke-related healthcare costs.
AB  - BACKGROUND: Limited data exist on the economic implications of stroke among
      patients with atrial fibrillation (AF). This study assesses the impact of AF on
      healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS),
      or transient ischemic attack (TIA). METHODS AND RESULTS: A retrospective analysis
      of MarketScan claims data (2005-2011) for AF patients >=18 years old with >=1
      inpatient claim for stroke, or >=1 ED or inpatient claim for TIA as identified by
      ICD-9-CM codes who had >=12 months continuous enrollment prior to initial stroke.
      Initial event- and stroke-related costs 12 months post-index were compared among
      patients with AF and without AF. Adjusted costs were estimated, controlling for
      demographics, comorbidities, anticoagulant use, and baseline resource use. Data
      from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted
      mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA
      hospitalization, and $3395 for TIA ED visit. After controlling for potential
      confounders, adjusted mean incremental costs (index plus 12-month post-index) for
      AF patients were higher than those for non-AF patients by: $4726, $7824, and
      $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and
      $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression
      analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in
      total stroke-related costs. CONCLUSION: Stroke-related care for IS, HS, and TIA
      is costly, especially among individuals with AF. Reducing the risk of AF-related
      stroke is important from both clinical and economic standpoints.

PMID- 24275633
TI  - The neurobiology of autism spectrum disorders.
AB  - Data is progressively and robustly accumulating regarding the biological basis of
      autism. Autism spectrum disorders (ASD) are currently considered a group of
      neurodevelopmental disorders with onset very early in life and a complex,
      heterogeneous, multifactorial aetiology. A comprehensive search of the last five
      years of the Medline database was conducted in order to summarize recent evidence
      on the neurobiological bases of autism. The main findings on genetic influence,
      neuropathology, neurostructure and brain networks are summarized. In addition,
      findings from peripheral samples of subjects with autism and animal models, which
      show immune, oxidative, mitochondrial dysregulations, are reported. Then, other
      biomarkers from very different systems associated with autism are reported.
      Finally, an attempt is made to try and integrate the available evidence, which
      points to a oligogenetic, multifactorial aetiology that converges in an aberrant
      micro-organization of the cortex, with abnormal functioning of the synapses and
      abnormalities in very general physiological pathways (such as inflammatory,
      immune and redox systems). 

PMID- 24275632
TI  - Early adoption of dabigatran and its dosing in US patients with atrial
      fibrillation: results from the outcomes registry for better informed treatment of
      atrial fibrillation.
AB  - BACKGROUND: Dabigatran is a novel oral anticoagulant approved for
      thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in
      community practice are unknown. METHODS AND RESULTS: We studied patterns of
      dabigatran use among patients enrolled in the Outcomes Registry for Better
      Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010
      and August 2011 and followed for 12 months. Among 9974 atrial fibrillation
      patients included, 1217 (12%) were treated with dabigatran during the study.
      Overall, patients receiving dabigatran were younger (median age 72 versus 75
      years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely
      to have private insurance (33% versus 25%, P<0.0001), and less likely to have
      prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset
      atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated
      risk based on the presence of congestive heart failure, hypertension, aged >=75
      years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0
      versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial
      Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25,
      56%) of patients with severe kidney disease were not prescribed reduced dosing,
      whereas 10% (n=91/920) with preserved renal function received lower dosing. Among
      patients not on dabigatran at baseline, 8% had dabigatran initiated during follow
      up. Patient education was significantly associated with switching from warfarin
      to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas
      antiarrhythmic drug use significantly correlated with de novo adoption of
      dabigatran (adjusted odds ratio 2.4, P<0.0001). CONCLUSIONS: Patients receiving
      dabigatran were younger and at a lower risk of stroke and bleeding. Patients
      appeared to drive switching from warfarin, whereas clinical characteristics
      influenced de novo start of dabigatran. These data suggest cautious early uptake
      of dabigatran, and more careful attention to dosing adjustments is warranted.
      CLINICAL TRIAL REGISTRATION URL: Clinicaltrials.gov. Unique identifier:
      NCT01165710.

PMID- 24275634
TI  - Multimodal Sensory Distortions in Postpartum Exacerbation of Schizophrenia.
AB  - BACKGROUND: Sensory distortions of body image commonly occur during migraine,
      seizures, nondominant cortical infarcts and hallucinogen abuse. METHODS: We
      report the case of a 30-year-old woman with paranoid schizophrenia presenting
      with postpartum onset multimodal sensory distortions in the absence of any
      neurological disorders or substance use. RESULTS: Her symptoms involved
      persistent facial/body metamorphopsia (distorted images) and vocal paracousis
      (distorted voices), in the absence of visual hallucinations, illusions or
      agnosia. Neuropsychological assessments revealed deficits on visual processing
      tasks. Neuroimaging, electroencephalography and ophthalmological evaluation
      revealed no abnormalities. The multimodal sensory distortions responded to
      antipsychotic treatment, paralleling improvement in other schizophrenia
      psychopathology, over a period of one month. CONCLUSIONS: Prominent and
      persistent multimodal sensory distortions like metamorphopsia and paracousis in
      the presence of psychotic symptoms warrant a detailed neurological and general
      medical work-up. These symptoms presenting in the absence of neurological or
      substance use disorders may be a component of schizophrenia.

PMID- 24275635
TI  - The Development and Implementation of an Electronic Health Record Tool for
      Monitoring Metabolic Syndrome Indices in Patients with Serious Mental Illness.
AB  - Objectives1. A quality performance improvement (QI) project to implement an
      electronic screening and monitoring tool to record components of the metabolic
      syndrome (e-MSD) during clinic visits by persons with serious mental illness
      (SMI). 2. To encourage psychiatrists to use this tool in their
      documentation.MethodsWorking with the information technology staff; five
      psychiatrists developed, tested, revised and embedded the e-MSD tool into the
      medication management document within the electronic health record. A continuing
      medical education program on metabolic syndrome was developed, and released to
      psychiatrists and mental health clinicians. Psychiatrist offices at one clinic
      were equipped with weighing scales, sphygmomanometers, waist circumference tapes
      and a QI project was initiated.ResultsAt one month, 9 to 12% of the
      anthropometric measures (height, weight, body mass index, waist circumference,
      and blood pressure) were recorded in 974 unique patient encounters, and 1 year
      later the numbers moved upwards - 15 to 41%. Towards the end of Year 1, a patient
      care associate was hired to measure the anthropometric measures, and one year
      later, the documented rates increased to 75-80%. Laboratory recordings (glucose
      and lipids) remained <= 8% throughout the first year, but moved upwards to 25% in
      Year 2.DiscussionNotwithstanding significant administrative and technical support
      for this QI project, changing clinician practice to screen, monitor and document
      metabolic indices in persons with SMI in the ambulatory setting changed
      significantly after the hiring of a patient care associate. Efforts to obtain
      laboratory measures in real-time remain a challenge. Next steps include
      interventions to promote weight loss and smoking cessation in SMI patients, and
      effective communication with their primary care doctors.

PMID- 24275636
TI  - Stressful life events, social class and symptoms of schizophrenia.
AB  - We test to see if severe stressful life events precede onset of specific symptoms
      of schizophrenia. Our analyses extend to possible variations in the effect by
      socioeconomic status (SES) of origin. The medical records of 431 schizophrenic
      patients were categorized into negative and positive subtypes by application of
      SANS, SAPS and PANS scales. SES was bifurcated into low SES and high SES groups.
      Stressful life events were classified into four domains. The study variables were
      tested by the use of chi-square analysis. Our results show that there is an
      elevated rate of positive symptoms among low SES patients who underwent a
      stressful life event before symptom onset. Significance is confirmed with a X2
      value of 5.418, p=.020. The finding does not hold true for high SES patients and
      is not related to type of stressful life event. Thus, we conclude that
      environmental stressors frequently precede onset of positive symptoms of
      schizophrenia. This is only true for patients of low SES of origin. We
      hypothesize that low SES patients have a heightened reactivity to stressors, a
      reactivity that is incubated by the human toll of impoverishment.

PMID- 24275630
TI  - Taking diabetes to heart--deregulation of myocardial lipid metabolism in diabetic
      cardiomyopathy.

PMID- 24275637
TI  - Fano-Kondo and the Kondo box regimes crossover in a quantum dot coupled to a
      quantum box.
AB  - In this work, we study the Kondo effect of a quantum dot (QD) connected to leads
      and to a discrete set of one-particle states provided by a quantum box
      represented by a quantum ring (QR) pierced by a magnetic flux side attached to
      the QD. The interplay between the bulk Kondo effect and the so-called Kondo box
      regime is studied. In this system the QR energies can be continuously modified by
      the application of the magnetic field. The crossover between these two regimes is
      analyzed by changing the connection of the QD to the QR from the weak to the
      strong coupling regime. In the weak coupling regime, the differential conductance
      develops a sequence of Fano-Kondo anti-resonances due to destructive interference
      between the discrete quantum ring levels and the conducting Kondo channel
      provided by the leads. In the strong coupling regime the differential conductance
      has very sharp resonances when one of the Kondo discrete sub-levels
      characterizing the Kondo box is tuned by the applied potential. The conductance,
      the current fluctuations and the Fano coefficient result as being the relevant
      physical magnitudes to be analyzed to reveal the physical properties of these two
      Kondo regimes and the crossover region between them. The results were obtained by
      using the slave boson mean field theory (SBMFT). 

PMID- 24275638
TI  - Development of lentiviral vectors for transient and stable protein overexpression
      in mammalian cells. A new strategy for recombinant human FVIII (rhFVIII)
      production.
AB  - BACKGROUND: Recombinant protein overexpression in mammalian cells constitutes a
      real challenge in therapeutic protein production. Following the discovery of
      intron functionality in gene expression, various expression vectors that include
      them in their sequences have been developed. In this study, the main goal was to
      develop new lentiviral vectors (LVs) carrying different promoter and intron
      containing 5'UTR (5' untranslated region) combinations and the design of LVs for
      rhFVIII production in Chinese hamster ovary (CHO) cells. RESULTS: By combining
      the human cytomegalovirus (CMV) or the elongation factor 1alpha (EF-1alpha)
      promoters along with different 5'UTRs that included leader introns, between 2 and
      12-fold increases were reached, when transient and stable expression of the
      enhanced green fluorescent protein (EGFP) and rhFVIII were analyzed. Also, new
      LVs provided with promoters and 5'UTRs from high expression genes, according to a
      gene database, were designed. Three of them were shown to be superior to the EF
      1alpha promoter in three widely used cell lines. CONCLUSION: In the present work,
      LVs containing different promoters and 5'UTRs were designed. In transient and
      stable assays some of these constructs have shown higher activity compared with
      commercial promoters and, therefore, constitute promising candidates for
      therapeutic protein production.

PMID- 24275639
TI  - Purification of a recombinant human growth hormone by an integrated IMAC
      procedure.
AB  - In this study, integration of three discrete process aspects of the IMAC
      purification of Escherichia coli expressed recombinant proteins has been
      investigated. To this end, novel N-terminally tagged human growth hormone
      variants (tagged-vhGHs) have been expressed in E. coli by tank fermentation and
      captured directly from the cell lysate by a new IMAC approach. The chelating
      ligands used were 1,4,7-triaza-cyclononane (tacn) and bis(1,4,7-triazacyclononyl)
      propane (dtnp) with copper(II) as the immobilised metal ion. The N-terminal tags
      were specifically selected for their potential to bind to these immobilised
      complexes and also for their ease of removal from the tagged protein by the
      dipeptidyl peptidase, DAP-1. Low levels of detergents in the binding buffer did
      not dramatically affect the purification, but increased concentrations of NaCl in
      the loading buffer improved the binding performance. The same IMAC systems,
      operated in the 'negative' adsorption chromatographic mode, could be used to
      obtain the purified mature human growth hormone variant, as assessed by MALDI-TOF
      and N-terminal sequencing studies, following removal of the affinity tag by the
      dipeptidyl peptidase 1. Western immunoblot analysis of the eluted fractions of
      both the tagged and de-tagged vhGH demonstrated significant clearance of E. coli
      host cell proteins (HCPs). Further, these IMAC resins can be used multiple times
      without the need for metal ion re-charging between runs. This study thus
      documents an integrated approach for the purification of specifically tagged
      recombinant proteins expressed in genetically modified E. coli. 

PMID- 24275640
TI  - Oxidative stress on cardiotoxicity after treatment with single and multiple doses
      of doxorubicin.
AB  - The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial.
      Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly
      assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8)
      and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to
      determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX
      (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1
      week after each injection (M1, M2, M3, and M4) to determine the chronological
      effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute
      study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology
      analyses were carried out at each time point. Single dose of DOX was associated
      with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks
      (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed
      an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R
      = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p =
      0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018),
      and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is
      associated with acute cardiotoxicity induced by a single dose of DOX only.
      Increased resistance to the oxidative stress is plausible for the multiple dose
      of DOX. Thus, different mechanisms may be involved in acute toxicity versus
      chronic toxicity. 

PMID- 24275641
TI  - Cytotoxicity evaluation of dentin contacting materials with dentin barrier test
      device using erbium-doped yttrium, aluminum, and garnet laser-treated dentin.
AB  - OBJECTIVES: The effect of dentin contacting materials on three-dimensional
      cultures of pulp-derived cells was evaluated in a dentin barrier test device
      using erbium-doped yttrium, aluminum, and garnet (Er:YAG) laser-treated dentin.
      METHODS: The test materials (iBond((r)), G-BondTM, and VitrebondTM) were applied
      on laser-treated or untreated dentin discs. After 24 h of exposure with perfusion
      of the test chamber, cell survival was evaluated by enzyme activity and related
      to a nontoxic control material. The mean values of control tissues were set to
      represent 100% viability. Data were analyzed using Kruskal-Wallis and Mann
      Whitney U test. RESULTS: Vitrebond was the most toxic material for both laser
      treated and untreated dentin. On untreated dentin, G-bond was cytotoxic to the
      pulp-derived cells (p < 0.05), and iBond was similar to the negative control
      group (p > 0.05). However, G-Bond and iBond were not cytotoxic when they were
      applied to Er:YAG laser-treated dentin (p > 0.05). CONCLUSION: Er:YAG laser
      treatment of dentin may protect the pulp cells from toxic substances of dentin
      contacting restorative materials; however, this effect is material related.
      Taking into consideration the limitations of this in vitro study, the Er:YAG
      laser treatment of dentin before restoration might be an option for decreasing
      the cytotoxic effects of the dental materials. Further research is required for
      clinical applications.

PMID- 24275642
TI  - Chromosomal damage in peripheral blood lymphocytes from nurses occupationally
      exposed to chemicals.
AB  - In the present study, we evaluated the induced genome damage in peripheral blood
      lymphocytes from a sample of nurses occupationally exposed to low doses of
      different chemicals. A comprehensive multi-biomarker approach using cytogenetic
      endpoints was employed for analyzing chromosomal aberrations (CAs) and sister
      chromatid exchange (SCE) assay. The study included 20 nurses and 20 control
      subjects matched in age, gender and smoking habits. Nurses were exposed to
      different chemicals, such as cytostatic drugs, anaesthetics, formaldehyde and
      other sterilizing gases. Significant differences were found between exposure
      group and control group in terms of SCEs frequency (p < 0.001) but not in terms
      of replication index value (p = 0.845) and CAs (p = 0.236). Regression analyses
      indicated that the age and the exposure years did not influence the amount of the
      chromosomal damage among nurses. Vice versa, among controls, a positive
      correlation was found between the number of SCEs and age. In conclusion, our
      results suggest that a continuous long-term exposure to low doses of chemicals
      could result in increased levels of SCEs among nurses. This data emphasize the
      importance of biomonitoring nurses and other hospital workers handling drugs. 

PMID- 24275643
TI  - Vaccination to prevent varicella: Goldman and King's response to Myers'
      interpretation of Varicella Active Surveillance Project data.
AB  - BACKGROUND: There is increasing evidence that herpes zoster (HZ) incidence rates
      among children and adults (aged <60 years) with a history of natural varicella
      are influenced primarily by the frequency of exogenous exposures, while
      asymptomatic endogenous reactivations help to cap the rate at approximately 550
      cases/100,000 person-years when exogenous boosting becomes rare. The Antelope
      Valley Varicella Active Surveillance Project was funded by the Centers for
      Disease Control and Prevention in 1995 to monitor the effects of varicella
      vaccination in one of the three representative regions of the United States. The
      stability in the data collection and number of reporting sites under varicella
      surveillance from 1995-2002 and HZ surveillance during 2000-2001 and 2006-2007
      contributed to the robustness of the discerned trends. DISCUSSION: Varicella
      vaccination may be useful for leukemic children; however, the target population
      in the United States is all children. Since the varicella vaccine inoculates its
      recipients with live, attenuated varicella-zoster virus (VZV), clinical varicella
      cases have dramatically declined. Declining exogenous exposures (boosts) from
      children shedding natural VZV have caused waning cell-mediated immunity. Thus,
      the protection provided by varicella vaccination is neither lifelong nor
      complete. Moreover, dramatic increases in the incidence of adult shingles cases
      have been observed since HZ was added to the surveillance in 2000. In 2013, this
      topic is still debated and remains controversial in the United States. SUMMARY:
      When the costs of the booster dose for varicella and the increased shingles
      recurrences are included, the universal varicella vaccination program is neither
      effective nor cost-effective.

PMID- 24275644
TI  - Crocin attenuates cisplatin-induced liver injury in the mice.
AB  - Cisplatin (CDDP) is one of the most frequently used antitumor agents, but its
      application is significantly limited by its hepatotoxicity. In the present study,
      we investigated the effects of crocin against CDDP-induced oxidative stress and
      apoptosis in the liver of Kunming mice. Crocin was administered to the mice once
      daily for 7 consecutive days at the doses of 6.25 and 12.5 mg/kg body weight
      orally. On day 1, a single intraperitoneal injection of CDDP was given at the
      dose of 10 mg/kg body weight. Crocin treatment significantly improved CDDP
      induced hepatic damage as indicated by serum aspartate aminotransferase and
      alanine aminotransferase levels. Crocin relieved CDDP-induced oxidative stress by
      reducing malondialdehyde level and recovering the levels of glutathione and
      antioxidant enzymes such as superoxide dismutase, catalase, and glutathione
      peroxidase. In addition, liver histopathology indicated that crocin alleviated
      CDDP-induced focal necrosis. Immunohistochemical staining and Western blot
      analysis showed that crocin significantly decreased the levels of phospho-p38
      mitogen-activated protein kinase (MAPK), tumor protein 53 (p53), and cleaved
      caspase-3. Taken together, our data suggest that crocin provides protective
      effects against CDDP-induced hepatoxicity by attenuating oxidative stress and
      inhibiting the activation of p38 MAPK, p53, and caspase-3. 

PMID- 24275645
TI  - Application of ultrasound-assisted emulsification microextraction for
      simultaneous determination of aminophenol isomers in human urine, hair dye, and
      water samples using high-performance liquid chromatography.
AB  - Aminophenol isomers (2-, 3-, and 4-aminophenols) are typically classified as
      industrial pollutants with genotoxic and mutagenic effects due to their easy
      penetration through the skin and membranes of human, animals, and plants. In the
      present study, a simple and efficient ultrasound-assisted emulsification
      microextraction procedure coupled with high-performance liquid chromatography
      with ultraviolet detector was developed for preconcentration and determination of
      these compounds in human fluid and environmental water samples. Effective
      parameters (such as type and volume of extraction solvent, pH and ionic strength
      of sample, and ultrasonication and centrifuging time) were investigated and
      optimized. Under optimum conditions (including sample volume: 5 mL; extraction
      solvent: chloroform, 80 uL; pH: 6.5; without salt addition; ultrasonication: 3.5
      min; and centrifuging time: 3 min, 5000 rpm min(-1)), the enrichment factors and
      limits of detection were ranged from 42 to 51 and 0.028 to 0.112 ug mL(-1),
      respectively. Once optimized, analytical performance of the method was studied in
      terms of linearity (0.085-157 ug mL(-1), r (2) > 0.998), accuracy (recovery =
      88.6- 101.7%), and precision (repeatability: intraday precision < 3.98%, and
      interday precision < 5.12%). Finally, applicability of the method was evaluated
      by the extraction and determination of these compounds in human urine, hair dye,
      and real water samples. 

PMID- 24275646
TI  - Orders out of chaos--molecular phylogenetics reveals the complexity of shark and
      stingray tapeworm relationships.
AB  - Novel molecular data are presented to resolve the long-standing issue of the non
      monophyly of the elasmobranch-hosted tapeworm order Tetraphyllidea relative to
      the other acetabulate eucestode orders. Bayesian inference analyses of various
      combinations of full ssrDNA, and full or partial lsrDNA (D1-D3), sequence data,
      which included 134 species representing 97 genera across the 15 eucestode orders,
      were conducted. New ssrDNA data were generated for 82 species, partial lsrDNA
      data for 53 species, and full lsrDNA data for 29 species. The monophyly of each
      of the elasmobranch-hosted orders Cathetocephalidea, Litobothriidea,
      Lecanicephalidea and Rhinebothriidea was confirmed, as was the non-monophyly of
      the Tetraphyllidea. Two relatively stable groups of tetraphyllidean taxa emerged
      and are hereby designated as new orders. The Onchoproteocephalidea n. ord. is
      established to recognise the integrated nature of one undescribed and 10
      described genera of hook-bearing tetraphyllideans, previously placed in the
      family Onchobothriidae, with the members of the order Proteocephalidea. The
      Phyllobothriidea n. ord. is established for a subset of 12 non-hooked genera
      characterised by scoleces bearing four bothridia each with an anterior accessory
      sucker; most parasitise sharks and have been assigned to the Phyllobothriidae at
      one time or another. Tentative ordinal placements are suggested for eight
      additional genera; placements for the remaining tetraphyllidean genera have not
      yet emerged. We propose that these 17 genera remain in the "Tetraphyllidea".
      Among these, particularly labile across analyses were Anthobothrium, Megalonchos,
      Carpobothrium, Calliobothrium and Caulobothrium. The unique association of
      Chimaerocestus with holocephalans, rather than with elasmobranchs, appears to
      represent a host-switching event. Both of the non-elasmobranch hosted clades of
      acetabulate cestodes (i.e. Proteocephalidea and Cyclophyllidea and their kin)
      appear to have had their origins with elasmobranch cestodes. Across analyses, the
      sister group to the clade of "terrestrial" cestode orders was found to be an
      elasmobranch-hosted genus, as was the sister to the freshwater fish- and tetrapod
      hosted Proteocephalidea. Whilst further data are required to resolve outstanding
      nomenclatural and phylogenetic issues, the present analyses contribute
      significantly to an understanding of the evolutionary radiation of the entire
      Cestoda. Clearly, elasmobranch tapeworms comprise the backbone of cestode
      phylogeny. 

PMID- 24275647
TI  - Arresting a Torsin ATPase reshapes the endoplasmic reticulum.
AB  - Torsins are membrane-tethered AAA+ ATPases residing in the nuclear envelope (NE)
      and endoplasmic reticulum (ER). Here, we show that the induction of a
      conditional, dominant-negative TorsinB variant provokes a profound reorganization
      of the endomembrane system into foci containing double membrane structures that
      are derived from the ER. These double-membrane sinusoidal structures are formed
      by compressing the ER lumen to a constant width of 15 nm, and are highly enriched
      in the ATPase activator LULL1. Further, we define an important role for a highly
      conserved aromatic motif at the C terminus of Torsins. Mutations in this motif
      perturb LULL1 binding, reduce ATPase activity, and profoundly limit the induction
      of sinusoidal structures. 

PMID- 24275648
TI  - Ouabain-induced internalization and lysosomal degradation of the Na+/K+-ATPase.
AB  - Internalization of the Na(+)/K(+)-ATPase (the Na(+) pump) has been studied in the
      human lung carcinoma cell line H1299 that expresses YFP-tagged alpha1 from its
      normal genomic localization. Both real-time imaging and surface biotinylation
      have demonstrated internalization of alpha1 induced by >=100 nm ouabain which
      occurs in a time scale of hours. Unlike previous studies in other systems, the
      ouabain-induced internalization was insensitive to Src or PI3K inhibitors.
      Accumulation of alpha1 in the cells could be augmented by inhibition of lysosomal
      degradation but not by proteosomal inhibitors. In agreement, the internalized
      alpha1 could be colocalized with the lysosomal marker LAMP1 but not with Golgi or
      nuclear markers. In principle, internalization could be triggered by a
      conformational change of the ouabain-bound Na(+)/K(+)-ATPase molecule or more
      generally by the disruption of cation homeostasis (Na(+), K(+), Ca(2+)) due to
      the partial inhibition of active Na(+) and K(+) transport. Overexpression of
      ouabain-insensitive rat alpha1 failed to inhibit internalization of human alpha1
      expressed in the same cells. In addition, incubating cells in a K(+)-free medium
      did not induce internalization of the pump or affect the response to ouabain.
      Thus, internalization is not the result of changes in the cellular cation balance
      but is likely to be triggered by a conformational change of the protein itself.
      In physiological conditions, internalization may serve to eliminate pumps that
      have been blocked by endogenous ouabain or other cardiac glycosides. This
      mechanism may be required due to the very slow dissociation of the
      ouabain.Na(+)/K(+)-ATPase complex. 

PMID- 24275649
TI  - Locking intracellular helices 2 and 3 together inactivates human P-glycoprotein.
AB  - The P-glycoprotein (P-gp) drug pump (ABCB1) has two transmembrane domains and two
      nucleotide-binding domains (NBDs). Coupling of the drug-binding sites in the
      transmembrane domains to the NBDs occurs through interaction of the intracellular
      helices (IHs) with residues in the NBDs (IH1/IH4/NBD1 and IH2/IH3/NBD2). We
      showed previously that cross-linking of cysteines in IH3 and IH1 with a short
      cross-linker mimicked drug binding as it activated P-gp ATPase activity. Here we
      show that residue A259C(IH2) could be directly cross-linked to W803C(IH3). Cross
      linking was inhibited by the presence of ATP and adenosine 5'-(beta,gamma
      imino)triphosphate but not by ADP. Cross-linking of mutant A259C/W803C inhibited
      its verapamil-stimulated ATPase activity mutant, but activity was restored after
      addition of dithiothreitol. Because these residues are close to the ball-and
      socket joint A266C(IH2)/Phe(1086)(NBD2), we mutated the adjacent Tyr(1087)(NBD2)
      close to IH3. Mutants Y1087A and Y1087L, but not Y1087F, were misprocessed, and
      all inhibited ATPase activity. Mutation of hydrophobic residues (F793A, L797A,
      L814A, and L818A) flanking IH3 also inhibited maturation. The results suggest
      that these residues, together with Trp(803) and Phe(804), form a large
      hydrophobic pocket. The results show that there is an important hydrophobic
      network at the IH2/IH3/NBD2 transmission interface that is critical for folding
      and activity of P-gp. 

PMID- 24275650
TI  - Functional analysis of light-harvesting-like protein 3 (LIL3) and its light
      harvesting chlorophyll-binding motif in Arabidopsis.
AB  - The light-harvesting complex (LHC) constitutes the major light-harvesting antenna
      of photosynthetic eukaryotes. LHC contains a characteristic sequence motif,
      termed LHC motif, consisting of 25-30 mostly hydrophobic amino acids. This motif
      is shared by a number of transmembrane proteins from oxygenic photoautotrophs
      that are termed light-harvesting-like (LIL) proteins. To gain insights into the
      functions of LIL proteins and their LHC motifs, we functionally characterized a
      plant LIL protein, LIL3. This protein has been shown previously to stabilize
      geranylgeranyl reductase (GGR), a key enzyme in phytol biosynthesis. It is
      hypothesized that LIL3 functions to anchor GGR to membranes. First, we conjugated
      the transmembrane domain of LIL3 or that of ascorbate peroxidase to GGR and
      expressed these chimeric proteins in an Arabidopsis mutant lacking LIL3 protein.
      As a result, the transgenic plants restored phytol-synthesizing activity. These
      results indicate that GGR is active as long as it is anchored to membranes, even
      in the absence of LIL3. Subsequently, we addressed the question why the LHC motif
      is conserved in the LIL3 sequences. We modified the transmembrane domain of LIL3,
      which contains the LHC motif, by substituting its conserved amino acids (Glu-171,
      Asn-174, and Asp-189) with alanine. As a result, the Arabidopsis transgenic
      plants partly recovered the phytol-biosynthesizing activity. However, in these
      transgenic plants, the LIL3-GGR complexes were partially dissociated.
      Collectively, these results indicate that the LHC motif of LIL3 is involved in
      the complex formation of LIL3 and GGR, which might contribute to the GGR
      reaction. 

PMID- 24275651
TI  - A catalytically essential motif in external loop 5 of the bacterial
      oligosaccharyltransferase PglB.
AB  - Asparagine-linked glycosylation is a post-translational protein modification that
      is conserved in all domains of life. The initial transfer of a lipid-linked
      oligosaccharide (LLO) onto acceptor asparagines is catalyzed by the integral
      membrane protein oligosaccharyltransferase (OST). The previously reported
      structure of a single-subunit OST enzyme, the Campylobacter lari protein PglB,
      revealed a partially disordered external loop (EL5), whose role in catalysis was
      unclear. We identified a new and functionally important sequence motif in EL5
      containing a conserved tyrosine residue (Tyr293) whose aromatic side chain is
      essential for catalysis. A synthetic peptide containing the conserved motif can
      partially but specifically rescue in vitro activity of mutated PglB lacking
      Tyr293. Using site-directed disulfide cross-linking, we show that disengagement
      of the structurally ordered part of EL5 is an essential step of the glycosylation
      reaction, probably by allowing sequon binding or glyco-product release. Our
      findings define two distinct mechanistic roles of EL5 in OST-catalyzed
      glycosylation. These functions, exerted by the two halves of EL5, are
      independent, because the loop can be cleaved by specific proteolysis with only
      slight reduction in activity.

PMID- 24275652
TI  - CD14 mediates Toll-like receptor 4 (TLR4) endocytosis and spleen tyrosine kinase
      (Syk) and interferon regulatory transcription factor 3 (IRF3) activation in
      epithelial cells and impairs neutrophil infiltration and Pseudomonas aeruginosa
      killing in vivo.
AB  - In the current study, we examined the role of CD14 in regulating LPS activation
      of corneal epithelial cells and Pseudomonas aeruginosa corneal infection. Our
      findings demonstrate that LPS induces Toll-like receptor 4 (TLR4) internalization
      in corneal epithelial cells and that blocking with anti-CD14 selectively inhibits
      TLR4 endocytosis, spleen tyrosine kinase (Syk) and IRF3 phosphorylation, and
      production of CCL5/RANTES and IFN-beta, but not IL-8. Using a murine model of P.
      aeruginosa corneal infection, we show that although infected CD14(-/-) corneas
      produce less CCL5, they exhibit significantly increased CXC chemokine production,
      neutrophil recruitment to the corneal stroma, and bacterial clearance than
      C57BL/6 mice. We conclude that CD14 has a critical role in mediating TLR4
      signaling through IRF3 in resident corneal epithelial cells and macrophages and
      thereby modulates TLR4 cell surface activation of the MyD88/NF-kappaB/AP-1
      pathway and production of CXC chemokines and neutrophil infiltration to infected
      tissues. 

PMID- 24275653
TI  - Molecular analysis of an alternative N-glycosylation machinery by functional
      transfer from Actinobacillus pleuropneumoniae to Escherichia coli.
AB  - N-Linked protein glycosylation is a frequent post-translational modification that
      can be found in all three domains of life. In a canonical, highly conserved
      pathway, an oligosaccharide is transferred by a membrane-bound
      oligosaccharyltransferase from a lipid donor to asparagines in the sequon NX(S/T)
      of secreted polypeptides. The delta-proteobacterium Actinobacillus
      pleuropneumoniae encodes an unusual pathway for N-linked protein glycosylation.
      This pathway takes place in the cytoplasm and is mediated by a soluble N
      glycosyltransferase (NGT) that uses nucleotide-activated monosaccharides to
      glycosylate asparagine residues. To characterize the process of cytoplasmic N
      glycosylation in more detail, we studied the glycosylation in A. pleuropneumoniae
      and functionally transferred the glycosylation system to Escherichia coli. N
      Linked glucose specific human sera were used for the analysis of the
      glycosylation process. We identified autotransporter adhesins as the preferred
      protein substrate of NGT in vivo, and in depth analysis of the modified sites in
      E. coli revealed a surprisingly relaxed peptide substrate specificity. Although
      NX(S/T) is the preferred acceptor sequon, we detected glycosylation of
      alternative sequons, including modification of glutamine and serine residues. We
      also demonstrate the use of NGT to glycosylate heterologous proteins. Therefore,
      our study could provide the basis for a novel route for the engineering of N
      glycoproteins in bacteria. 

PMID- 24275654
TI  - A direct interaction between leucine-rich repeat kinase 2 and specific beta
      tubulin isoforms regulates tubulin acetylation.
AB  - Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat
      kinase 2 (LRRK2), are a common cause of Parkinson disease. LRRK2 has been
      suggested to influence the cytoskeleton as LRRK2 mutants reduce neurite outgrowth
      and cause an accumulation of hyperphosphorylated Tau. This might cause
      alterations in the dynamic instability of microtubules suggested to contribute to
      the pathogenesis of Parkinson disease. Here, we describe a direct interaction
      between LRRK2 and beta-tubulin. This interaction is conferred by the LRRK2 Roc
      domain and is disrupted by the familial R1441G mutation and artificial Roc domain
      mutations that mimic autophosphorylation. LRRK2 selectively interacts with three
      beta-tubulin isoforms: TUBB, TUBB4, and TUBB6, one of which (TUBB4) is mutated in
      the movement disorder dystonia type 4 (DYT4). Binding specificity is determined
      by lysine 362 and alanine 364 of beta-tubulin. Molecular modeling was used to map
      the interaction surface to the luminal face of microtubule protofibrils in close
      proximity to the lysine 40 acetylation site in alpha-tubulin. This location is
      predicted to be poorly accessible within mature stabilized microtubules, but
      exposed in dynamic microtubule populations. Consistent with this finding,
      endogenous LRRK2 displays a preferential localization to dynamic microtubules
      within growth cones, rather than adjacent axonal microtubule bundles. This
      interaction is functionally relevant to microtubule dynamics, as mouse embryonic
      fibroblasts derived from LRRK2 knock-out mice display increased microtubule
      acetylation. Taken together, our data shed light on the nature of the LRRK2
      tubulin interaction, and indicate that alterations in microtubule stability
      caused by changes in LRRK2 might contribute to the pathogenesis of Parkinson
      disease. 

PMID- 24275655
TI  - Homo-oligomerization of the activating natural killer cell receptor NKp30
      ectodomain increases its binding affinity for cellular ligands.
AB  - The natural cytotoxicity receptors, comprised of three type I membrane proteins
      NKp30, NKp44, and NKp46, are a unique set of activating proteins expressed mainly
      on the surface of natural killer (NK) cells. Among these, NKp30 is a major
      receptor targeting virus-infected cells, malignantly transformed cells, and
      immature dendritic cells. To date, only few cellular ligands of NKp30 have been
      discovered, and the molecular details of ligand recognition by NKp30 are poorly
      understood. Within the current study, we found that the ectodomain of NKp30 forms
      functional homo-oligomers that mediate high affinity binding to its corresponding
      cellular ligand B7-H6. Notably, this homo-oligomerization is strongly promoted by
      the stalk domain of NKp30. Based on these data, we suggest that homo
      oligomerization of NKp30 in the plasma membrane of NK cells, which might be
      favored by IL-2-dependent up-regulation of NKp30 expression, provides a way to
      improve recognition and lysis of target cells by NK cells. 

PMID- 24275656
TI  - Crystal structures of the Toll/Interleukin-1 receptor (TIR) domains from the
      Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular
      mimicry.
AB  - The Toll/IL-1 receptor (TIR) domains are crucial innate immune signaling modules.
      Microbial TIR domain-containing proteins inhibit Toll-like receptor (TLR)
      signaling through molecular mimicry. The TIR domain-containing protein TcpB from
      Brucella inhibits TLR signaling through interaction with host adaptor proteins
      TIRAP/Mal and MyD88. To characterize the microbial mimicry of host proteins, we
      have determined the X-ray crystal structures of the TIR domains from the Brucella
      protein TcpB and the host adaptor protein TIRAP. We have further characterized
      homotypic interactions of TcpB using hydrogen/deuterium exchange mass
      spectrometry and heterotypic TcpB and TIRAP interaction by co-immunoprecipitation
      and NF-kappaB reporter assays. The crystal structure of the TcpB TIR domain
      reveals the microtubule-binding site encompassing the BB loop as well as a
      symmetrical dimer mediated by the DD and EE loops. This dimerization interface is
      validated by peptide mapping through hydrogen/deuterium exchange mass
      spectrometry. The human TIRAP TIR domain crystal structure reveals a unique N
      terminal TIR domain fold containing a disulfide bond formed by Cys(89) and
      Cys(134). A comparison between the TcpB and TIRAP crystal structures reveals
      substantial conformational differences in the region that encompasses the BB
      loop. These findings underscore the similarities and differences in the molecular
      features found in the microbial and host TIR domains, which suggests mechanisms
      of bacterial mimicry of host signaling adaptor proteins, such as TIRAP. 

PMID- 24275657
TI  - Polarity and charge of the periplasmic loop determine the YidC and sec
      translocase requirement for the M13 procoat lep protein.
AB  - During membrane biogenesis, the M13 procoat protein is inserted into the lipid
      bilayer in a strictly YidC-dependent manner with both the hydrophobic signal
      sequence and the membrane anchor sequence promoting translocation of the
      periplasmic loop via a hairpin mechanism. Here, we find that the translocase
      requirements can be altered for PClep in a predictable manner by changing the
      polarity and charge of the peptide region that is translocated across the
      membrane. When the polarity of the translocated peptide region is lowered and the
      charged residues in this region are removed, translocation of this loop region
      occurs largely by a YidC- and Sec-independent mechanism. When the polarity is
      increased to that of the wild-type procoat protein, the YidC insertase is
      essential for translocation. Further increasing the polarity, by adding charged
      residues, switches the insertion pathway to a YidC/Sec mechanism. Conversely, we
      find that increasing the hydrophobicity of the transmembrane segments of PClep
      can decrease the translocase requirement for translocation of the peptide chain.
      This study provides a framework to understand why the YidC and Sec machineries
      exist in parallel and demonstrates that the YidC insertase has a limited capacity
      to translocate a peptide chain on its own. 

PMID- 24275658
TI  - Mitogen-activated protein kinase-mediated licensing of interferon regulatory
      factor 3/7 reinforces the cell response to virus.
AB  - The induction of the intrinsic antiviral defense in mammals relies on the
      accumulation of foreign genetic material. As such, complete engagement of this
      response is limited to replication-competent viruses. Interferon regulatory
      factors (IRFs) are mediators of this defense with shared enhancer elements but
      display a spectrum of transcriptional potential. Here we describe a mechanism
      designed to enhance this response should a pathogen not be successfully
      inhibited. We find that activation of IRF7 results in the induction of MAP3K8 and
      restructuring of the antiviral transcriptome. MAP3K8 mediates the phosphorylation
      and repression of IRF3 homodimers to promote greater transcriptional activity
      through utilization of IRF3:IRF7 heterodimers. Among the genes influenced by the
      MAP3K8/IRF7 signaling axis are members of the SP100 gene family that serve as
      general transcriptional enhancers of the antiviral defense. We propose that this
      feed forward loop serves to reinforce the cellular response and is reserved for
      imminent threats to the host. 

PMID- 24275659
TI  - The c-FLIPL cleavage product p43FLIP promotes activation of extracellular signal
      regulated kinase (ERK), nuclear factor kappaB (NF-kappaB), and caspase-8 and T
      cell survival.
AB  - Caspase-8 is now appreciated to govern both apoptosis following death receptor
      ligation and cell survival and growth via inhibition of the Ripoptosome. Cells
      must therefore carefully regulate the high level of caspase-8 activity during
      apoptosis versus the modest levels observed during cell growth. The caspase-8
      paralogue c-FLIP is a good candidate for a molecular rheostat of caspase-8
      activity. c-FLIP can inhibit death receptor-mediated apoptosis by competing with
      caspase-8 for recruitment to FADD. However, full-length c-FLIPL can also
      heterodimerize with caspase-8 independent of death receptor ligation and activate
      caspase-8 via an activation loop in the C terminus of c-FLIPL. This triggers
      cleavage of c-FLIPL at Asp-376 by caspase-8 to produce p43FLIP. The continued
      function of p43FLIP has, however, not been determined. We demonstrate that acute
      deletion of endogenous c-FLIP in murine effector T cells results in loss of
      caspase-8 activity and cell death. The lethality and caspase-8 activity can both
      be rescued by the transgenic expression of p43FLIP. Furthermore, p43FLIP
      associates with Raf1, TRAF2, and RIPK1, which augments ERK and NF-kappaB
      activation, IL-2 production, and T cell proliferation. Thus, not only is c-FLIP
      the initiator of caspase-8 activity during T cell activation, it is also an
      initial caspase-8 substrate, with cleaved p43FLIP serving to both stabilize
      caspase-8 activity and promote activation of pathways involved with T cell
      growth. 

PMID- 24275660
TI  - Structural basis for autoinhibition of CTP:phosphocholine cytidylyltransferase
      (CCT), the regulatory enzyme in phosphatidylcholine synthesis, by its membrane
      binding amphipathic helix.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) interconverts between an inactive
      soluble and active membrane-bound form in response to changes in membrane lipid
      composition. Activation involves disruption of an inhibitory interaction between
      the alphaE helices at the base of the active site and an autoinhibitory (AI)
      segment in the regulatory M domain and membrane insertion of the M domain as an
      amphipathic helix. We show that in the CCT soluble form the AI segment functions
      to suppress kcat and elevate the Km for CTP. The crystal structure of a CCT dimer
      composed of the catalytic and AI segments reveals an AI-alphaE interaction as a
      cluster of four amphipathic helices (two alphaE and two AI helices) at the base
      of the active sites. This interaction corroborates mutagenesis implicating
      multiple hydrophobic residues within the AI segment that contribute to its
      silencing function. The AI-alphaE interaction directs the turn at the C-terminal
      end of the AI helix into backbone-to-backbone contact with a loop (L2) at the
      opening to the active site, which houses the key catalytic residue, lysine 122.
      Molecular dynamics simulations suggest that lysine 122 side-chain orientations
      are constrained by contacts with the AI helix-turn, which could obstruct its
      engagement with substrates. This work deciphers how the CCT regulatory
      amphipathic helix functions as a silencing device. 

PMID- 24275661
TI  - The RNA-binding protein HuD regulates autophagosome formation in pancreatic beta
      cells by promoting autophagy-related gene 5 expression.
AB  - Tight regulation of autophagy is critical for the fate of pancreatic beta cells.
      The autophagy protein ATG5 is essential for the formation of autophagosomes by
      promoting the lipidation of microtubule-associated protein LC3 (light chain 3).
      However, little is known about the mechanisms that regulate ATG5 expression
      levels. In this study, we investigated the regulation of ATG5 expression by HuD.
      The association of HuD with ATG5 mRNA was analyzed by ribonucleoprotein complex
      immunoprecipitation and biotin pulldown assays. HuD expression levels in
      pancreatic beta cells were knocked down via siRNA, elevated by overexpression of
      a HuD-expressing plasmid. The expression levels of HuD, ATG5, LC3, and beta-actin
      were determined by Western blot and quantitative RT-PCR analysis. Autophagosome
      formation was assessed by fluorescence microscopy in GFP-LC3-expressing cells and
      in pancreatic tissues from WT and HuD-null mice. We identified ATG5 mRNA as a
      post-transcriptional target of the mammalian RNA-binding protein HuD in
      pancreatic beta cells. HuD associated with the 3'-UTR of the ATG5 mRNA.
      Modulating HuD abundance did not alter ATG5 mRNA levels, but HuD silencing
      decreased ATG5 mRNA translation, and, conversely, HuD overexpression enhanced
      ATG5 mRNA translation. Through its effect on ATG5, HuD contributed to the
      lipidation of LC3 and the formation of LC3-positive autophagosomes. In keeping
      with this regulatory paradigm, HuD-null mice displayed lower ATG5 and LC3 levels
      in pancreatic beta cells. Our results reveal HuD to be an inducer of ATG5
      expression and hence a critical regulator of autophagosome formation in
      pancreatic beta cells. 

PMID- 24275662
TI  - Tetramers are the activation-competent species of the HOCl-specific transcription
      factor HypT.
AB  - Hypochlorous acid (HOCl) is an important component of the immune system and is
      produced by neutrophils to kill invading microorganisms. The transcription factor
      HypT is specifically activated by HOCl by methionine oxidation and protects
      Escherichia coli cells from the detrimental effects of HOCl. HypT forms
      dodecameric ring-like oligomers. Binding of HypT to DNA induces dissociation of
      the dodecamers into dimers and tetramers, thus forming the DNA-binding species.
      To dissect HypT dissociation, binding to DNA, and activation, we aimed to
      dissociate the dodecamers independently of DNA and to analyze HOCl-dependent
      activation in vitro. We found that HypT dodecamers dissociated into tetramers in
      the presence of l-arginine and NaCl, which was reversible upon dilution of the
      additive. Making use of the reversible dissociation, we generated mixed
      assemblies consisting of wild-type and mutant HypT subunits and determined that
      mutant subunits with reduced thermal stability were stabilized by wild-type HypT
      in the mixed assembly. HypT tetramers, as present at high NaCl concentrations,
      were stabilized against thermal unfolding and aggregation triggered by high HOCl
      concentrations. Importantly, in vitro activation by HOCl of HypT tetramers was
      completed within 1 min, whereas activation of dodecamers required 1 h for
      completion. Furthermore, activation of HypT tetramers required stoichiometric
      amounts of HOCl instead of an excess of HOCl, as observed for dodecamers. This
      supports the idea that small HypT oligomers are the activation-competent species,
      whereas the dodecamers are a storage form. Our study reveals the importance of
      the dynamic oligomeric state for HypT activation by HOCl. 

PMID- 24275663
TI  - Leishmania donovani prevents oxidative burst-mediated apoptosis of host
      macrophages through selective induction of suppressors of cytokine signaling
      (SOCS) proteins.
AB  - One of the mechanisms for establishment of infection employed by intra-macrophage
      pathogen-like Leishmania is inhibition of oxidative burst-mediated macrophage
      apoptosis to protect their niche for survival and replication. We tried to
      elucidate the underlying mechanism for this by using H2O2 for induction of
      apoptosis. Leishmania donovani-infected macrophages were much more resistant to
      H2O2-mediated apoptosis compared with control. Although infected cells were
      capable of comparable reactive oxygen species production, there was less
      activation of the downstream cascade consisting of caspase-3 and -7 and cleaved
      poly(ADP)-ribose polymerase. Suppressors of cytokine signaling (SOCS) 1 and 3
      proteins and reactive oxygen species scavenging enzyme thioredoxin, known to be
      involved in stabilization of protein-tyrosine phosphatases, were found to be
      induced during infection. Induction of SOCS proteins may be mediated by Egr1, and
      silencing of Socs1 and -3 either alone or in combination resulted in reduced
      thioredoxin levels, enhanced activation of caspases, and increased apoptosis of
      infected macrophages. The induction of protein-tyrosine phosphatases,
      thioredoxin, SOCS, and Egr1 in L. donovani-infected macrophages was found to be
      unaffected by H2O2 treatment. SOCS knocked down cells also displayed decreased
      parasite survival thus marking reduction in disease progression. Taken together,
      these results suggest that L. donovani may exploit SOCS for subverting macrophage
      apoptotic machinery toward establishing its replicative niche inside the host. 

PMID- 24275664
TI  - Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor
      necrosis factor-alpha in macrophages.
AB  - The haptoglobin-hemoglobin receptor CD163 and proTNF-alpha are transmembrane
      macrophage proteins subjected to cleavage by the inflammation-responsive protease
      ADAM17. This leads to release of soluble CD163 (sCD163) and bioactive TNF-alpha.
      Sequence comparison of the juxtamembrane region identified similar palindromic
      sequences in human CD163 ((1044)Arg-Ser-Ser-Arg) and proTNF-alpha ((78)Arg-Ser
      Ser-Ser-Arg). In proTNF-alpha the Arg-Ser-Ser-Ser-Arg sequence is situated next
      to the previously established ADAM17 cleavage site. Site-directed mutagenesis
      revealed that the sequences harbor essential information for efficient cleavage
      of the two proteins upon ADAM17 stimulation. This was further evidenced by
      analysis of mouse CD163 that, like CD163 in other non-primates, does not contain
      the palindromic CD163 sequence in the juxtamembrane region. Mouse CD163 resisted
      endotoxin- and phorbol ester-induced shedding, and ex vivo analysis of knock-in
      of the Arg-Ser-Ser-Arg sequence in mouse CD163 revealed a receptor shedding
      comparable with that of human CD163. In conclusion, we have identified an
      essential substrate motif for ADAM17-mediated CD163 and proTNF-alpha cleavage in
      macrophages. In addition, the present data indicate that CD163, by incorporation
      of this motif in late evolution, underwent a modification that allows for an
      instant down-regulation of surface CD163 expression and inhibition of hemoglobin
      uptake. This regulatory modality seems to have coincided with the evolution of an
      enhanced hemoglobin-protecting role of the haptoglobin-CD163 system in primates. 

PMID- 24275665
TI  - Antisense oligonucleotide-stimulated transcriptional pausing reveals RNA exit
      channel specificity of RNA polymerase and mechanistic contributions of NusA and
      RfaH.
AB  - Transcript elongation by bacterial RNA polymerase (RNAP) is thought to be
      regulated at pause sites by open versus closed positions of the RNAP clamp
      domain, pause-suppressing regulators like NusG and RfaH that stabilize the closed
      clampRNAP conformation, and pause-enhancing regulators like NusA and exit channel
      nascent RNA structures that stabilize the open clamp RNAP conformation. However,
      the mutual effects of these protein and RNA regulators on RNAP conformation are
      incompletely understood. For example, it is unknown whether NusA directly
      interacts with exit channel duplexes and whether formation of exit channel
      duplexes and RfaH binding compete by favoring the open and closed RNAP
      conformations. We report new insights into these mechanisms using antisense
      oligonucleotide mimics of a pause RNA hairpin from the leader region of the his
      biosynthetic operon of enteric bacteria like Escherichia coli. By systematically
      varying the structure and length of the oligonucleotide mimic, we determined that
      full pause stabilization requires an RNA-RNA duplex of at least 8 bp or a DNA-RNA
      duplex of at least 11 bp; RNA-RNA duplexes were more effective than DNA-RNA. NusA
      stimulation of pausing was optimal with 10-bp RNA-RNA duplexes and was aided by
      single-stranded RNA upstream of the duplex but was significantly reduced with DNA
      RNA duplexes. Our results favor direct NusA stabilization of exit channel
      duplexes, which consequently affect RNAP clamp conformation. Effects of RfaH,
      which suppresses oligo-stabilization of pausing, were competitive with antisense
      oligonucleotide concentration, suggesting that RfaH and exit channel duplexes
      compete via opposing effects on RNAP clamp conformation.

PMID- 24275666
TI  - Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) promotes
      breast cancer progression through enhancing glucose starvation-induced autophagy
      and Akt signaling.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of
      cell growth and proliferation. Recent studies have suggested that constitutive
      activation of mTORC1 in normal cells could lead to malignant tumor development in
      several tissues. However, the mechanisms of mTORC1 hyperactivation to promote the
      growth and metastasis of breast or other cancers are still not well
      characterized. Here, using a new inducible deletion system, we show that deletion
      of Tsc1 in mouse primary mammary tumor cells, either before or after their
      transplantation, significantly increased their growth in vivo. The increase in
      tumor growth was completely rescued by rapamycin treatment, suggesting a major
      contribution from mTORC1 hyperactivation. Interestingly, glucose starvation
      induced autophagy, but not amino acid starvation-induced autophagy, was increased
      significantly in Tsc1-null tumor cells. Further analysis of these cells also
      showed an increased Akt activation but no significant changes in Erk signaling.
      Together, these results provide insights into the mechanism by which
      hyperactivation of mTORC1 promotes breast cancer progression through increasing
      autophagy and Akt activation in vivo. 

PMID- 24275668
TI  - Food consumption by young children: a function of parental feeding goals and
      practices.
AB  - Staggering health implications are associated with poor child diet. Given the
      importance of parents in impacting children's eating outcomes, the current study
      examined a theoretical framework in which both parental feeding goals and
      practices impact specific healthy and unhealthy child eating behaviors.
      Participants were 171 mothers of 3-6year old children who were diverse both
      socioeconomically and with regard to BMI. Mothers completed questionnaires via
      Mechanical Turk, an online workforce through Amazon.com. Structural Equation
      Modeling showed an adequate model fit in which Negative Feeding Practices (e.g.,
      using food as a reward) mediated the relationship between Health-Related Feeding
      Goals (i.e., feeding children with health-oriented goals in mind) and Negative
      Eating Behaviors (e.g., consumption of candy and snacks). However, Negative
      Feeding Practices did not mediate the relationship between Health-Related Feeding
      Goals and Positive Eating Behaviors (i.e., fruits and vegetables). These findings
      suggest the important role of habitual food parenting practices in children's
      eating and have implications for parental health education programs. 

PMID- 24275667
TI  - Small peptides blocking inhibition of factor Xa and tissue factor-factor VIIa by
      tissue factor pathway inhibitor (TFPI).
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that
      inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue
      factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa
      complex. Inhibition of TFPI enhances coagulation in hemophilia models. Using a
      library approach, we selected and subsequently optimized peptides that bind TFPI
      and block its anticoagulant activity. One peptide (termed compound 3), bound with
      high affinity to the Kunitz-1 (K1) domain of TFPI (Kd ~1 nM). We solved the
      crystal structure of this peptide in complex with the K1 of TFPI at 2.55-A
      resolution. The structure of compound 3 can be segmented into a N-terminal
      anchor; an Omega-shaped loop; an intermediate segment; a tight glycine-loop; and
      a C-terminal alpha-helix that is anchored to K1 at its reactive center loop and
      two-stranded beta-sheet. The contact surface has an overall hydrophobic character
      with some charged hot spots. In a model system, compound 3 blocked FXa inhibition
      by TFPI (EC50 = 11 nM) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI
      (EC50 = 2 nM). The peptide prevented transition from the loose to the tight FXa
      TFPI complex, but did not affect formation of the loose FXa-TFPI complex. The K1
      domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa.
      Because compound 3 binds to K1, our data show that K1 is not only important for
      FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the
      loose to the tight FXa-TFPI complex. This mode of action translates into
      normalization of coagulation of hemophilia plasmas. Compound 3 thus bears
      potential to prevent bleeding in hemophilia patients.

PMID- 24275669
TI  - Relationships between expected, online and remembered enjoyment for food
      products.
AB  - How enjoyable a food product is remembered to be is likely to shape future
      choice. The present study tested the influence that expectations and specific
      moments during consumption experiences have on remembered enjoyment for food
      products. Sixty-four participants consumed three snack foods (savoury, sweet and
      savoury-sweet) and rated expected and online enjoyment for each product. Twenty
      four hours later participants rated remembered enjoyment and future expected
      enjoyment for each product. Remembered enjoyment differed to online enjoyment for
      two of the three products, resulting in the foods being remembered as less
      enjoyable than they actually were. Both expected enjoyment and specific moments
      during the consumption experience (e.g. the least enjoyable mouthful) influenced
      remembered enjoyment. However, the factors that shaped remembered enjoyment were
      not consistent across the different food products. Remembered enjoyment was also
      shown to be a better predictor of future expected enjoyment than online
      enjoyment. Remembered enjoyment is likely to influence choice behaviour and can
      be discrepant to actual enjoyment. Specific moments during a consumption
      experience can have disproportionately large influence on remembered enjoyment
      (whilst others are neglected), but the factors that determine which moments
      influence remembered enjoyment are unclear. 

PMID- 24275670
TI  - Chocolate cake. Guilt or celebration? Associations with healthy eating attitudes,
      perceived behavioural control, intentions and weight-loss.
AB  - Food and eating are often associated with ambivalent feelings: pleasure and
      enjoyment, but also worry and guilt. Guilt has the potential to motivate
      behaviour change, but may also lead to feelings of helplessness and loss of
      control. This study firstly examined whether a default association of either
      'guilt' or 'celebration' with a prototypical forbidden food item (chocolate cake)
      was related to differences in attitudes, perceived behavioural control, and
      intentions in relation to healthy eating, and secondly whether the default
      association was related to weight change over an 18month period (and short term
      weight-loss in a subsample of participants with a weight-loss goal). This study
      did not find any evidence for adaptive or motivational properties of guilt.
      Participants associating chocolate cake with guilt did not report more positive
      attitudes or stronger intentions to eat healthy than did those associating
      chocolate cake with celebration. Instead, they reported lower levels of perceived
      behavioural control over eating and were less successful at maintaining their
      weight over an 18month period. Participants with a weight-loss goal who
      associated chocolate cake with guilt were less successful at losing weight over a
      3month period compared to those associating chocolate cake with celebration. 

PMID- 24275671
TI  - Fecal microbiota transplantation for Clostridium difficile infection: benefits
      and barriers.
AB  - PURPOSE OF REVIEW: The incidence and severity of Clostridium difficile infection
      (CDI) have increased worldwide in the past two decades. A principal function of
      the gut microbiota is to protect the intestine against colonization by exogenous
      pathogens. Increasingly, the gut microbiota have been shown to influence
      susceptibility to other genetic and environmentally acquired conditions.
      Transplantation of healthy donor fecal material in patients with CDI may re
      establish the normal composition of the gut microbiota and has been shown to be
      effective in recurrent CDI. We intend to review the most recent data on fecal
      microbiota transplantation (FMT) and critically discuss potential advantages and
      handicaps of this new therapeutic approach. RECENT FINDINGS: Evidence from case
      series and only one randomized clinical trial suggests that FMT is able to
      restore the wide diversity of microflora, improve C. difficile-related symptoms
      and prevent CDI recurrence. SUMMARY: FMT is a promising treatment option for
      serious and recurrent CDI, and current evidence (although weak) demonstrates
      consistent and excellent efficacy in clinical outcomes. However, many questions
      should be answered before it may be recommended as routine standard treatment.
      Mechanisms of action need to be better understood. Long-term follow-up studies
      are needed to determine long-lasting effects (including the association with
      autoimmune diseases).

PMID- 24275672
TI  - Emerging infectious colitis.
AB  - PURPOSE OF REVIEW: The present review will highlight recent advances in the
      knowledge of emerging pathogens causing infectious colitis and provide a
      description of the most important food-borne outbreaks. RECENT FINDINGS:
      Outbreaks of enteric disease caused by Salmonella spp., Campylobacter spp., and
      Shiga toxin-producing Escherichia coli (STEC) continue to surprise with new
      epidemiological findings or changing virulence characteristics. These pathogens
      evolve to exploit novel opportunities for spread and transmission, such as fresh
      produce within the food chain, and generate new public health challenges. Organic
      sprouts were recently considered as the source responsible for a large German
      disease outbreak comprising 3842 patients. The outbreak strain was identified as
      an enteroaggregative STEC O104:H4 (EAggC), a rare hybrid pathogen that harbours
      the phage encoded Shiga toxin gene and antibiotic resistance in an EAggEC
      background. Clostridium difficile PCR ribotype 078 is emerging across Europe,
      causing severe disease outside healthcare facilities as well as disease in farm
      animals, indicating that the species border has been crossed. Although the global
      impact of cryptosporidiosis is less pronounced, these organisms have been
      responsible for large outbreaks of infectious diarrhoea, often not reported.
      Invasive listeriosis is a serious food-borne illness and was found recently in 28
      US states affecting 147 patients, associated with eating contaminated cantaloupe.
      Outbreaks of gastroenteritis caused by Listeria monocytogenes are most likely
      severely underestimated. Centralized surveillance of food-borne enteropathogens
      is essential for the early detection of disease outbreaks and for the
      organization of an immediate and appropriate response. SUMMARY: An improved
      understanding of the pathogenesis, pathology and epidemiology of emerging
      enteropathogens causing infectious colitis will provide new approaches for
      disease prevention and control.

PMID- 24275674
TI  - Relationship between CD4 cell count and serious long-term complications among HIV
      positive individuals.
AB  - PURPOSE OF REVIEW: To summarize recent findings on the relationship between CD4
      cell count metrics and selected serious clinical outcomes, and to deduce
      implications for CD4 cell count monitoring in treated HIV infection and the
      timing of combination antiretroviral therapy initiation. RECENT FINDINGS: In
      treated HIV infection, a higher latest CD4 cell count is associated with a lower
      short-term risk of serious non-AIDS events (often composite endpoints) even in
      CD4 cell count strata more than 350/MUl. Knowledge of alternate CD4 cell count
      metrics, such as CD4 cell count slope, nadir level and time spent under specific
      CD4 cell count thresholds, does not seem to confer additional prognostic
      information beyond that achieved by current CD4 cell count. Latest CD4 cell count
      is strongly associated with a short-term risk of infection-related non-AIDS
      malignancies, and serious hepatic events; however, the evidence is inconsistent
      for cardiovascular outcomes. Studies vary significantly in definitions of
      composite endpoints as well as the rigorousness of outcome ascertainment, which
      could explain the heterogeneity in results. SUMMARY: Current CD4 cell count, but
      not other metrics, could be an important clinical tool to predict the short-term
      risk of serious non-AIDS events in treated HIV-positive individuals. An earlier
      initiation of therapy at CD4 cell count more than 350/MUl or above 500/MUl is
      likely to improve long-term CD4 cell count metrics. Whether it provides net
      individual clinical benefit requires a randomized trial.

PMID- 24275673
TI  - Markers of coagulation and inflammation often remain elevated in ART-treated HIV
      infected patients.
AB  - PURPOSE OF REVIEW: Current antiretroviral therapies have dramatically changed the
      disease course of HIV infection. Although antiretroviral therapy is effective at
      decreasing viral replication and preserving CD4 T-cell numbers, low-level immune
      activation and inflammation persist in virally suppressed HIV-infected patients.
      This chronic immune activation/inflammation may contribute to an increased risk
      for venous and arterial thrombosis. RECENT FINDINGS: Several markers of
      coagulation and inflammation are increased in HIV-infected patients. The
      Strategies for the Management of Antiretroviral Therapy study reported that
      plasma D-dimer levels, a marker of fibrinolysis, independently predicted
      morbidity in HIV-infected patients. Increased plasma and cell surface levels of
      the procoagulant tissue factor have also been reported in patients with HIV
      disease. Fibrinogen, von Willebrand factor, and P-selectin are likewise increased
      in plasma samples of HIV-infected patients; all of these markers suggest HIV
      infection results in a procoagulant state. Treatment with antiretroviral therapy
      reduces, but does not always normalize, levels of biomarkers associated with
      inflammation and coagulation in HIV+ patients. SUMMARY: HIV-infected patients are
      at greater risk for both venous and arterial thrombosis. Chronic immune
      activation and inflammation in these patients appears to contribute to
      coagulation risk. Antiretroviral therapy reduces viral replication, immune
      activation, and markers of coagulation, but these indices do not always return to
      normal, even after several years of viremic control.

PMID- 24275675
TI  - Can antiretroviral therapy prevent HIV-associated cognitive disorders?
AB  - PURPOSE OF REVIEW: In general, the initiation of combination antiretroviral
      (cART) is associated with improvement in cognitive function. However, the impact
      of cART has on cognitive function in neurologically asymptomatic HIV-infected
      individuals initiating therapy at high CD4 lymphocyte cell counts is unknown.
      RECENT FINDINGS: Cognitive function impairment remains prevalent despite
      effective cART. Several clinical risk factors for this condition have been
      described, including low nadir CD4 lymphocyte cell count which may be associated
      with greater neuroinflammatory process, a potential pathogenic mechanism
      underlying this cognitive impairment. The earlier initiation of antiretroviral
      therapy could theoretically avoid this risk factor and limit the degree of
      neuroinflammation. On the converse, the earlier initiation of cART may be
      associated with the development of neuronal toxicities. SUMMARY: This review
      article highlights the recent literature and arguments for and against the
      earlier initiation of cART with regards to cognitive function.

PMID- 24275677
TI  - Differing effects of denosumab and alendronate on cortical and trabecular bone.
AB  - Vertebral fractures and trabecular bone loss are hallmarks of osteoporosis.
      However, 80% of fractures are non-vertebral and 70% of all bone loss is cortical
      and is produced by intracortical remodeling. The resulting cortical porosity
      increases bone fragility exponentially. Denosumab, a fully human anti-RANKL
      antibody, reduces the rate of bone remodeling more than alendronate. The aim of
      this study was to quantify the effects of denosumab and alendronate on cortical
      and trabecular bone. Postmenopausal women, mean age 61years (range 50 to 70),
      were randomized double blind to placebo (n=82), alendronate 70mg weekly (n=82),
      or denosumab 60mg every 6months (n=83) for 12months. Porosity of the compact
      appearing cortex (CC), outer and inner cortical transitional zones (OTZ, ITZ),
      and trabecular bone volume/total volume (BV/TV) of distal radius were quantified
      in vivo from high-resolution peripheral quantitative computed tomography scans.
      Denosumab reduced remodeling more rapidly and completely than alendronate,
      reduced porosity of the three cortical regions at 6months, more so by 12months
      relative to baseline and controls, and 1.5- to 2-fold more so than alendronate.
      The respective changes at 12months were [mean (95% CI)]; CC: -1.26% (-1.61, 
      0.91) versus -0.48% (-0.96, 0.00), p=0.012; OTZ: -1.97% (-2.37, -1.56) versus 
      0.81% (-1.45, -0.17), p=0.003; and ITZ: -1.17% (-1.38, -0.97) versus -0.78% (
      1.04, -0.52), p=0.021. Alendronate reduced porosity of the three cortical regions
      at 6months relative to baseline and controls but further decreased porosity of
      only the ITZ at 12months. By 12months, CC porosity was no different than baseline
      or controls, OTZ porosity was reduced only relative to baseline, not controls,
      while ITZ porosity was reduced relative to baseline and 6months, but not
      controls. Each treatment increased trabecular BV/TV volume similarly: 0.25%
      (0.19, 0.30) versus 0.19% (0.13, 0.30), p=0.208. The greater reduction in
      cortical porosity by denosumab may be due to greater inhibition of intracortical
      remodeling. Head to head studies are needed to determine whether differences in
      porosity result in differing fracture outcomes. 

PMID- 24275676
TI  - Initiation of antiretroviral therapy at high CD4 cell counts: does it reduce the
      risk of cardiovascular disease?
AB  - PURPOSE OF REVIEW: Inflammation and immune activation associated with untreated
      HIV infection may increase the risk for cardiovascular disease (CVD) and are not
      entirely reversed by antiretroviral therapy (ART). Although older ART regimens
      were associated with drug-specific risks for CVD, this may not be true for modern
      ART. Thus, with regard to CVD risk, the net benefit of initiating ART at higher
      CD4 T-cell counts remains unclear. RECENT FINDINGS: In addition to the well
      established risk of coronary heart disease, emerging evidence now suggests that
      chronic HIV infection is associated with higher risk of ischemic stroke, heart
      failure, and arrhythmias. These epidemiologic studies have associated
      immunodeficiency and active viral replication with higher CVD risk. Novel methods
      of imaging subclinical vascular disease continue to implicate inflammation and
      immune activation as likely mediators of CVD among patients with HIV. Newer
      generation protease inhibitors, chemokine receptor 5 antagonists, and integrase
      inhibitors do not appear to be associated with the adverse cardiometabolic risks
      of older drugs. SUMMARY: Recent evidence suggests that treating HIV infection
      with ART may reduce the risk of CVD, even at higher CD4 T-cell counts; however,
      the definitive answer to this question will come from clinical trials and long
      term observational studies.

PMID- 24275678
TI  - Standardized serum GM-CSF autoantibody testing for the routine clinical diagnosis
      of autoimmune pulmonary alveolar proteinosis.
AB  - Autoantibodies against granulocyte/macrophage colony-stimulating factor (GMAbs)
      cause autoimmune pulmonary alveolar proteinosis (PAP) and measurement of the GMAb
      level in serum is now commonly used to identify this disease, albeit, in a
      clinical research setting. The present study was undertaken to optimize and
      standardize serum GMAb concentration testing using a GMAb enzyme-linked
      immunosorbent assay (GMAb ELISA) to prepare for its introduction into routine
      clinical use. The GMAb ELISA was evaluated using serum specimens from autoimmune
      PAP patients, healthy people, and GMAb-spiked serum from healthy people. After
      optimizing assay components and procedures, its accuracy, precision, reliability,
      sensitivity, specificity, and ruggedness were evaluated. The coefficient of
      variation in repeated measurements was acceptable (<15%) for well-to-well, plate
      to-plate, day-to-day, and inter-operator variation, and was not affected by
      repeated freeze-thaw cycles of serum specimens or the reference standards, or by
      storage of serum samples at -80 degrees C. The lower limit of quantification
      (LLOQ) of the PAP patient-derived polyclonal GMAb reference standard (PCRS) was
      0.78ng/ml. Receiver operating characteristic curve analysis identified a serum
      GMAb level of 5MUg/ml (based on PCRS) as the optimal cut off value for
      distinguishing autoimmune PAP serum from normal serum. A pharmaceutical-grade,
      monoclonal GMAb reference standard (MCRS) was developed as the basis of a new
      unit of measure for GMAb concentration: one International Unit (IU) of GMAb is
      equivalent to 1MUg/ml of MCRS. The median [interquartile range] serum GMAb level
      was markedly higher in autoimmune PAP patients than in healthy people (21.54
      [12.83-36.38] versus 0.08 [0.05-0.14] IU; n=56, 38; respectively; P<0.0001).
      Results demonstrate that serum GMAb measurement using the GMAb ELISA was
      accurate, precise, reliable, had an acceptable LLOQ, and could be accurately
      expressed in standardized units. These findings support the use of this GMAb
      ELISA for the routine clinical diagnosis of autoimmune PAP and introduce a new
      unit of measure to enable standardized reporting of serum GMAb data from
      different laboratories. 

PMID- 24275679
TI  - The impact of pre-analytical variables on the stability of neurofilament proteins
      in CSF, determined by a novel validated SinglePlex Luminex assay and ELISA.
AB  - BACKGROUND: Neurofilament (Nf) proteins have been shown to be promising
      biomarkers for monitoring and predicting disease progression for various
      neurological diseases. The aim of this study was to evaluate the effects of pre
      analytical variables on the concentration of neurofilament heavy (NfH) and
      neurofilament light (NfL) proteins. METHODS: For NfH an in-house newly-developed
      and validated SinglePlex Luminex assay was used; ELISA was used to analyze NfL.
      RESULTS: For the NfL ELISA assay, the intra- and inter-assay variation was
      respectively, 1.5% and 16.7%. Analytical performance of the NfH SinglePlex
      Luminex assay in terms of sensitivity (6.6pg/mL), recovery in cerebrospinal fluid
      (CSF) (between 90 and 104%), linearity (from 6.6-1250pg/mL), and inter- and intra
      assay variation (<8%) were good. Concentrations of both NfL and NfH appeared not
      negatively affected by blood contamination, repeated freeze-thaw cycles (up to
      4), delayed processing (up to 24hours) and during long-term storage at -20
      degrees C, 4 degrees C, and room temperature. A decrease in concentration was
      observed during storage of both neurofilament proteins up to 21days at 37 degrees
      C, which was significant by day 5. CONCLUSIONS: The newly developed NfH
      SinglePlex Luminex assay has a good sensitivity and is robust. Moreover, both NfH
      and NfL are stable under the most prevalent pre-analytical variations.

PMID- 24275682
TI  - Lipids: atherosclerosis begins "shortly after birth" in children with FH.

PMID- 24275680
TI  - Hysteria, race, and phlogiston. A model of ontological elimination in the human
      sciences.
AB  - Elimination controversies are ubiquitous in philosophy and the human sciences.
      For example, it has been suggested that human races, hysteria, intelligence,
      mental disorder, propositional attitudes such as beliefs and desires, the self,
      and the super-ego should be eliminated from the list of respectable entities in
      the human sciences. I argue that eliminativist proposals are often presented in
      the framework of an oversimplified "phlogiston model" and suggest an alternative
      account that describes ontological elimination on a gradual scale between
      criticism of empirical assumptions and conceptual choices. 

PMID- 24275683
TI  - Coronary artery disease: noninvasive imaging technique can identify high-risk
      coronary plaques.

PMID- 24275684
TI  - Risk factors: insights from the REGARDS study.

PMID- 24275687
TI  - Interventional cardiology: biodegradable-polymer DES versus second-generation
      durable-polymer DES.

PMID- 24275688
TI  - Prevention: coronary artery calcium and polypill therapy.

PMID- 24275689
TI  - Inhibitors of CXC chemokine receptor type 4: putative therapeutic approaches in
      inflammatory diseases.
AB  - PURPOSE OF REVIEW: The CXC chemokine receptor type 4 (CXCR4), which is a G
      protein coupled receptor, and its ligand CXCL12 play an important role in
      neutrophil homeostasis and inflammation. This review focuses on involvement of
      the CXCL12/CXCR4 axis in inflammation and different inflammatory diseases and
      depicts that blocking CXCR4 is an attractive therapeutic strategy. RECENT
      FINDINGS: Binding of CXCL12 to CXCR4 retains immature neutrophils in the bone
      marrow and also participates in leukocyte recruitment into inflamed tissue. The
      CXCL12/CXCR4 axis is also involved in several inflammatory processes and diseases
      including the WHIM (warts, hypogammaglobulinemia, infections and myelokathexis)
      syndrome, HIV, autoimmune disorders, ischemic injury, and pulmonary fibrosis.
      SUMMARY: Based on these findings, blocking CXCR4 seems to be a therapeutic
      strategy in inflammatory diseases. Several promising CXCR4 antagonists are in
      different stages of development and clinical trials. Currently, only plerixafor
      (AMD3100) has been approved for short-term application.

PMID- 24275690
TI  - Defensins in innate immunity.
AB  - PURPOSE OF REVIEW: Defensins are a major family of antimicrobial peptides
      expressed predominantly in neutrophils and epithelial cells, and play important
      roles in innate immune defense against infectious pathogens. Their biological
      functions in and beyond innate immunity, structure and activity relationships,
      mechanisms of action, and therapeutic potential continue to be interesting
      research topics. This review examines recent progress in our understanding of
      alpha and theta-defensins - the two structural classes composed of members of
      myeloid origin. RECENT FINDINGS: A novel mode of antibacterial action is
      described for human enteric alpha-defensin 6, which forms structured nanonets to
      entrap bacterial pathogens and protect against bacterial invasion of the
      intestinal epithelium. The functional multiplicity and mechanistic complexity of
      defensins under different experimental conditions contribute to a debate over the
      role of enteric alpha-defensins in mucosal immunity against HIV-1 infection.
      Contrary to common belief, hydrophobicity rather than cationicity plays a
      dominant functional role in the action of human alpha-defensins; hydrophobicity
      mediated high-order assembly endows human alpha-defensins with an extraordinary
      ability to acquire structural diversity and functional versatility. Growing
      evidence suggests that theta-defensins offer the best opportunity for therapeutic
      development as a novel class of broadly active anti-infective and anti
      inflammatory agents. SUMMARY: Defensins are the 'Swiss army knife' in innate
      immunity against microbial pathogens. Their modes of action are often reminiscent
      of the story of 'The Blind Men and the Elephant'. The functional diversity and
      mechanistic complexity, as well as therapeutic potential of defensins, will
      continue to attract attention to this important family of antimicrobial peptides.

PMID- 24275691
TI  - Neutrophils and type 1 autoimmune diabetes.
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) is commonly portrayed as an autoimmune
      disease, in which misguided T lymphocyte activities cause selective destruction
      of insulin-producing pancreatic beta-cells. New findings suggest that the
      immunological picture might be more complex than previously imagined. This review
      will focus on the recent studies that provide new insight into the hypothesis
      that neutrophils might participate in T1D initiation and perpetuation. RECENT
      FINDINGS: Reduced circulating neutrophil counts associate with T1D in humans from
      the pre-diabetic to the onset phases. Additionally, a hitherto unacknowledged
      role for neutrophils in T1D pathogenesis has recently been demonstrated in mice
      with spontaneous autoimmune T1D. SUMMARY: Although these findings have yet to
      undergo the scrutiny of the scientific community, they suggest that neutrophils -
      in addition to macrophages, dendritic cells, and lymphocytes - may play a role in
      T1D immunopathology. Further research is needed, which might lead to the
      definition of new therapeutic strategies for a disease that to date has proved
      controllable but incurable.

PMID- 24275692
TI  - Understanding neutropenia.

PMID- 24275693
TI  - Correlation and interaction visualization of altmetric indicators extracted from
      scholarly social network activities: dimensions and structure.
AB  - BACKGROUND: Citation counts for peer-reviewed articles and the impact factor of
      journals have long been indicators of article importance or quality. In the Web
      2.0 era, growing numbers of scholars are using scholarly social network tools to
      communicate scientific ideas with colleagues, thereby making traditional
      indicators less sufficient, immediate, and comprehensive. In these new
      situations, the altmetric indicators offer alternative measures that reflect the
      multidimensional nature of scholarly impact in an immediate, open, and
      individualized way. In this direction of research, some studies have demonstrated
      the correlation between altmetrics and traditional metrics with different
      samples. However, up to now, there has been relatively little research done on
      the dimension and interaction structure of altmetrics. OBJECTIVE: Our goal was to
      reveal the number of dimensions that altmetric indicators should be divided into
      and the structure in which altmetric indicators interact with each other.
      METHODS: Because an article-level metrics dataset is collected from scholarly
      social media and open access platforms, it is one of the most robust samples
      available to study altmetric indicators. Therefore, we downloaded a large dataset
      containing activity data in 20 types of metrics present in 33,128 academic
      articles from the application programming interface website. First, we analyzed
      the correlation among altmetric indicators using Spearman rank correlation.
      Second, we visualized the multiple correlation coefficient matrixes with
      graduated colors. Third, inputting the correlation matrix, we drew an MDS diagram
      to demonstrate the dimension for altmetric indicators. For correlation structure,
      we used a social network map to represent the social relationships and the
      strength of relations. RESULTS: We found that the distribution of altmetric
      indicators is significantly non-normal and positively skewed. The distribution of
      downloads and page views follows the Pareto law. Moreover, we found that the
      Spearman coefficients from 91.58% of the pairs of variables indicate statistical
      significance at the .01 level. The non-metric MDS map divided the 20 altmetric
      indicators into three clusters: traditional metrics, active altmetrics, and
      inactive altmetrics. The social network diagram showed two subgroups that are
      tied to each other but not to other groups, thus indicating an intersection
      between altmetrics and traditional metric indicators. CONCLUSIONS: Altmetrics
      complement, and most correlate significantly with, traditional measures.
      Therefore, in future evaluations of the social impact of articles, we should
      consider not only traditional metrics but also active altmetrics. There may also
      be a transfer phenomenon for the social impact of academic articles. The impact
      transfer path has transfer, or intermediate, stations that transport and
      accelerate article social impact from active altmetrics to traditional metrics
      and vice versa. This discovery will be helpful to explain the impact transfer
      mechanism of articles in the Web 2.0 era. Hence, altmetrics are in fact superior
      to traditional filters for assessing scholarly impact in multiple dimensions and
      in terms of social structure.

PMID- 24275694
TI  - Management of Trypanosoma cruzi coinfection in HIV-positive individuals outside
      endemic areas.
AB  - PURPOSE OF THE REVIEW: Chagas disease has spread beyond the geographical barriers
      of the American continent in the past decade. Consequently, physicians treating
      HIV-infected patients in nonendemic countries have to face an opportunistic
      infection they have little experience with. This review examines the literature
      on Chagas disease in HIV-infected patients, with special emphasis on recent
      findings. RECENT FINDINGS: Although infection by Trypanosoma cruzi is a severe
      opportunistic infection in HIV-infected patients, awareness of this parasitosis
      in nonendemic countries remains low. Deeply immunosuppressed patients with
      chronic infection can develop reactivations, which can be very severe and are
      associated with high mortality. Reactivations mostly affect the central nervous
      system, followed by the heart, and diagnosis is based on the direct detection of
      the parasite or histology. There is no reliable method of predicting
      reactivations. Treatment is based on benzimidazoles, although neither the
      appropriate treatment schedule nor the need for secondary prophylaxis has been
      clearly established. Antiretroviral therapy seems to play a fundamental role in
      the prevention of reactivations and control of relapses; however, more
      information is needed. SUMMARY: Many aspects of T. cruzi-HIV coinfection remain
      uncertain. Until new data covering the current gaps become available, early
      diagnosis and prompt antiretroviral therapy seem to be fundamental for avoiding
      reactivations and improving late visceral involvement.

PMID- 24275695
TI  - Eradicating syphilis, hepatitis C and HIV in MSM through frequent testing
      strategies.
AB  - PURPOSE OF REVIEW: The rates of sexual transmission of HIV, syphilis and
      hepatitis C in MSM are rising in most countries. Recent research has raised the
      question of whether increasing testing and treatment of these infections could
      substantially reduce their transmission. RECENT FINDINGS: Although mathematical
      models suggest this strategy could be potentially effective in reducing
      transmission, there is currently very limited evidence that community-wide
      incidence has been curtailed by this strategy. SUMMARY: If increasing in testing
      is to substantially reduce the incidence of these infections then significant
      increases in testing are required together with innovative approaches to testing
      and healthcare delivery. Notwithstanding this, relatively simple approaches to
      increasing testing are currently underutilized.

PMID- 24275696
TI  - Global resistance of Neisseria gonorrhoeae: when theory becomes reality.
AB  - PURPOSE OF REVIEW: Neisseria gonorrhoeae has demonstrated a remarkable genetic
      capacity to acquire antimicrobial resistance (AMR) determinants. This review
      focuses on the recent developments in respect of third generation extended
      spectrum cephalosporin (ESC)-resistant gonorrhoea and the search for future
      treatment options. RECENT FINDINGS: The estimated incidence of new gonorrhoea
      cases is increasing, and the antimicrobial resistance profile of N. gonorrhoeae
      is worsening. The most significant recent finding has been the emergence of
      extensively drug-resistant (XDR) N. gonorrhoeae characterized by very high
      ceftriaxone minimum inhibitory concentrations. A national switch from cefixime to
      high-dose ceftriaxone as first-line antigonococcal therapy in England and Wales,
      as well as parts of Japan, has been accompanied by a reduction in the prevalence
      of oral ESC-resistant gonococci. Azithromycin given in combination with either
      gentamicin or gemifloxacin has been shown to be an effective alternative
      antigonococcal therapy. Both ertapenem and solithromycin have good in-vitro
      activity against ESC-resistant N. gonorrhoeae strains. SUMMARY: Current
      strategies to control gonococcal AMR should focus on the use of higher doses of
      ceftriaxone given as part of dual therapy and further evaluation of alternative
      drug combinations. The emergence of XDR gonorrhoea argues for enhanced efforts to
      develop novel antimicrobial agents and a gonococcal vaccine.

PMID- 24275697
TI  - Asymptomatic bacteriuria.
AB  - PURPOSE OF REVIEW: Asymptomatic bacteriuria is a common finding. Inappropriate
      antimicrobial treatment of asymptomatic bacteriuria has been identified as a
      major issue for antimicrobial stewardship programs. This review summarizes and
      evaluates recent studies which extend our knowledge of the occurrence,
      management, and outcomes of bacteriuria. RECENT FINDINGS: The reported prevalence
      of bacteriuria is higher in some developing countries than generally reported for
      developed countries, but reasons for this remain unclear. Clinical studies of
      young women, renal transplant patients, and patients undergoing minor
      nontraumatic urologic procedures confirm that treatment of asymptomatic
      bacteriuria for these populations is not beneficial, and may be harmful. There is
      also no benefit for treatment of asymptomatic bacteriuria prior to orthopedic
      surgery to decrease postoperative surgical site infection. Studies continue to
      report substantial inappropriate antimicrobial use for treatment of asymptomatic
      bacteriuria. SUMMARY: Recent publications confirm that asymptomatic bacteriuria
      is benign in most patients. Management strategies for pregnant women with
      recurrent bacteriuria require further clarification. There is a continuing
      problem with inappropriate treatment of asymptomatic bacteriuria, and sustainable
      strategies to optimize antimicrobial use for this problem are needed.

PMID- 24275698
TI  - Defining and measuring negative symptoms of schizophrenia in clinical trials.
AB  - Recent attention has focused on negative symptoms as a target for new therapeutic
      approaches including pharmacological agents, medical devices, and psychosocial
      treatments. Each of these approaches requires an instrument for measuring the
      severity of negative symptoms as well as changes in severity over time. The
      instrument selected should provide coverage for the domains of negative symptoms;
      it should be sensitive to change; it should be reliable and relatively brief; and
      it should be useful for large international trials. These criteria were used to
      evaluate a number of older instruments including the Schedule for the Assessment
      of Negative Symptoms (SANS), the Positive and Negative Symptoms Scale (PANSS),
      and the Negative Symptom Assessment Scale (NSA). Two newer scales, the Brief
      Negative Symptom Scale (BNSS) and the Clinical Assessment Interview for Negative
      Symptoms (CAINS) were developed following a National Institute of Mental Health
      consensus meeting and addressed some of the shortcomings of earlier instruments. 

PMID- 24275699
TI  - Negative symptoms of schizophrenia: clinical features, relevance to real world
      functioning and specificity versus other CNS disorders.
AB  - Negative symptoms have long been recognized as a central feature of the
      phenomenology of schizophrenia, dating back to the early descriptions by
      Kraepelin and Bleuler. Over the ensuing century, there have been important
      clarifications and reconceptualizations regarding the phenomenology of negative
      symptoms in schizophrenia. This review explores these developments, including the
      delineation of two underlying subdomains of negative symptoms - amotivation
      (i.e., avolition/apathy and asociality) and diminished expression (i.e., poverty
      of speech and affective flattening). Further, advances in our understanding of
      specific motivational and hedonic deficits seen in schizophrenia are explored.
      The findings that negative symptoms stand apart from depressive and cognitive
      symptoms in schizophrenia are also discussed. In terms of the predictors of
      functional outcomes in schizophrenia, we explore both the direct role of negative
      symptoms in this regard, as well as their indirect role through cognition. We
      then broaden our examination of negative symptoms to related disorders across the
      schizophrenia spectrum, as well as to other neuropsychiatric illnesses, where
      negative symptoms have been increasingly recognized. We explore the differential
      characteristics of negative symptoms across these illnesses, and their relevance
      to functional outcomes. This transdiagnostic presence and relevance of negative
      symptoms highlights the need for continued exploration of their phenomenology and
      neurobiology as we move to develop effective interventions to address these
      debilitating symptoms and improve functional outcomes.

PMID- 24275700
TI  - Effects of lithium and aripiprazole on brain stimulation reward and
      neuroplasticity markers in the limbic forebrain.
AB  - Bipolar disorder (BD) is a severe pathological condition with impaired reward
      related processing. The present study was designed to assess the effects of two
      commonly used BD medications, the mood stabilizer lithium chloride (LiCl) and the
      atypical antipsychotic and antimanic agent aripiprazole, in an animal model of
      reward and motivation and on markers of neuroplasticity in the limbic forebrain
      in rats. We utilized intracranial self-simulation (ICSS) to assess the effects of
      acute and chronic administration of LiCl and aripiprazole on brain stimulation
      reward, and phosphorylation studies to determine their effects on specific
      cellular neuroplasticity markers, i.e., the phosphorylation of CREB and crucial
      phosphorylation sites on the GluA1 subunit of AMPA receptors and the NA1 and NA2B
      subunits of NMDA receptors, in the limbic forebrain. Chronic LiCl induced
      tolerance to the anhedonic effect of the drug observed after acute
      administration, while chronic aripiprazole induced a sustained anhedonic effect.
      These distinct behavioral responses might be related to differences in molecular
      markers of neuroplasticity. Accordingly, we demonstrated that chronic LiCl, but
      not aripiprazole, decreased phosphorylation of CREB at the Ser133 site and NA1 at
      the Ser896 site in the prefrontal cortex and GluA1 at the Ser831 site and NA2B at
      the Ser1303 site in the ventral striatum. The present study provides evidence for
      BD medication-evoked changes in reward and motivation processes and in specific
      markers of neuronal plasticity in the limbic forebrain, promoting the notion that
      these drugs may blunt dysregulated reward processes in BD by counteracting
      neuronal plasticity deficits.

PMID- 24275702
TI  - Opening of a Peierls gap in BaVS3 probed by V L3 edge resonant inelastic x-ray
      scattering.
AB  - V L3 edge resonant inelastic x-ray scattering measurements performed on high
      quality BaVS3 single crystals reveal that the intra-t2g dd excitations close to
      the elastic peak are suppressed below the metal-insulator transition induced by
      the Peierls instability. The depletion of electronic states close to the Fermi
      level represents a direct observation of the opening of a charge gap inside the
      t2g manifold. 

PMID- 24275703
TI  - Adherence and persistence in the use of warfarin after hospital discharge among
      patients with heart failure and atrial fibrillation.
AB  - BACKGROUND: Postdischarge adherence and long-term persistence in the use of
      warfarin among patients with heart failure and atrial fibrillation without
      contraindications have not been fully described. METHODS AND RESULTS: We
      identified patients with heart failure and atrial fibrillation who were >= 65
      years old, eligible for warfarin, and discharged home from hospitals in the Get
      With the Guidelines-Heart Failure registry from January 1, 2006, to December 31,
      2009. We used linked Medicare prescription drug event data to measure adherence
      and persistence. The main outcome measures were rates of prescription at
      discharge, outpatient dispensing, discontinuation, and adherence as measured by
      the medication possession ratio. We hypothesized that adherence to warfarin would
      differ according to whether patients received the prescription at discharge.
      Among 2,691 eligible patients, 1,856 (69.0%) were prescribed warfarin at
      discharge. Patients prescribed warfarin at discharge had significantly higher
      prescription fill rates within 90 days (84.5% vs 12.3%; P < .001) and 1 year
      (91.6% vs 16.8%; P < .001) and significantly higher medication possession ratios
      (0.78 vs 0.63; P < .001). Among both previous nonusers and existing users, fill
      rates at 90 days and 1 year and possession ratios were significantly higher among
      those prescribed warfarin at discharge. CONCLUSIONS: One-third of eligible
      patients with heart failure and atrial fibrillation were not prescribed warfarin
      at discharge from a heart failure hospitalization, and few started therapy as
      outpatients. In contrast, most patients who were prescribed warfarin at discharge
      filled the prescription within 90 days and remained on therapy at 1 year.

PMID- 24275704
TI  - The evolution of substrate differentiation in Minuartia series Laricifoliae
      (Caryophyllaceae) in the European Alps: In situ origin or repeated colonization?
AB  - PREMISE OF THE STUDY: Substrate specialization is often considered an important
      factor in evolutionary diversification. A classic example of divergence related
      to different substrate types is the dichotomy between calcicole and calcifuge
      plants on calcareous and siliceous substrates as found in the European Alps. When
      closely related species with contrasting substrate preferences are found in the
      same area, it is generally hypothesized that they diverged where they now occur.
      However, it is possible that Alpine edaphic diversity instead allows the
      coexistence of related species whose edaphic differentiation took place deeper in
      the phylogeny, in some other part of the range of their clades. METHODS: We used
      sequences of the nuclear internal and external transcribed spacer regions to
      examine the origin of substrate differentiation in Minuartia series Laricifoliae,
      which contains many edaphic endemics, including a pair of Alpine taxa with
      contrasting substrate preferences: Minuartia langii (calcicole) and M.
      laricifolia (calcifuge). KEY RESULTS: MINUARTIA LANGII and M. laricifolia are
      each more closely related to Balkan species than they are to each other and
      reached the Alps independently. The clade to which they belong is ancestrally
      calcicole. Minuartia langii inherited the ancestral ecology, while M. laricifolia
      is part of a subclade with serpentine endemics and one substrate generalist.
      CONCLUSIONS: In the study group, taxa with contrasting substrate preferences did
      not diverge in the Alps. Instead, taxa whose substrate differentiation arose
      elsewhere, likely on the Balkan Peninsula, were preadapted to take advantage of
      Alpine substrate diversity.

PMID- 24275705
TI  - Phylogenetic lineages in Vanguerieae (Rubiaceae) associated with Burkholderia
      bacteria in sub-Saharan Africa.
AB  - PREMISE OF THE STUDY: It is well known that mutualistic bacteria can provide
      substantial benefits to their host plants. However, 'how,' 'why,' and the
      possible applications of such an interaction are only second to the questions
      'who is involved?', and 'where does it occur?'. In the coffee family (Rubiaceae),
      certain species closely interact with endophytic leaf bacteria that are freely
      distributed among the mesophyll cells. This type of interaction was recently
      discovered in South Africa. Our aim is to document the bacterial diversity
      associated with Rubiaceae ('who') and to establish the geographic range of the
      interaction ('where'). METHODS: Representatives of the Vanguerieae tribe in
      Rubiaceae were investigated for the presence of endophytes with special emphasis
      on the distributional range of the plant-bacteria association by collecting
      specimens from different African regions. KEY RESULTS: The interaction is found
      in five genera and is restricted to three major host lineages. The endophytic
      bacteria belong to the genus Burkholderia and are part of the plant-associated
      beneficial and environmental group. Some endophytes are similar to B. caledonica,
      B. graminis, B. phenoliruptrix or B. phytofirmans, while others are classified in
      OTUs that show no similarity with any previously described Burkholderia species
      of bacteria. CONCLUSIONS: The association is not obligate from the bacterial
      point of view and is considered a loose and recent interaction, which is
      demonstrated by the fact that there is no evidence for coevolution. The
      geographical distribution of the association is restricted by the distributional
      range of the host plants covering the whole of sub-Saharan Africa.

PMID- 24275707
TI  - Desert dust and human health disorders.
AB  - Dust storms may originate in many of the world's drylands and have an effect not
      only on human health in the drylands themselves but also in downwind
      environments, including some major urban centres, such as Phoenix, Kano, Athens,
      Madrid, Dubai, Jedda, Tehran, Jaipur, Beijing, Shanghai, Seoul, Taipei, Tokyo,
      Sydney, Brisbane and Melbourne. In some parts of the world dust storms occur
      frequently throughout the year. They can transport particulate material,
      pollutants, and potential allergens over thousands of km from source. The main
      sources include the Sahara, central and eastern Asia, the Middle East, and parts
      of the western USA. In some parts of the world, though not all, the frequency of
      dust storms is changing in response to land use and climatic changes, and in such
      locations the health implications may become more severe. Data on the PM10 and
      P2.5 loadings of dust events are discussed, as are various pollutants (heavy
      metals, pesticides, etc.) and biological components (spores, fungi, bacteria,
      etc.). Particulate loadings can far exceed healthy levels. Among the human health
      effects of dust storms are respiratory disorders (including asthma, tracheitis,
      pneumonia, allergic rhinitis and silicosis) cardiovascular disorders (including
      stroke), conjunctivitis, skin irritations, meningococcal meningitis, valley
      fever, diseases associated with toxic algal blooms and mortality and injuries
      related to transport accidents. 

PMID- 24275708
TI  - Native liver histology after successful portoenterostomy in biliary atresia.
AB  - BACKGROUND: Biliary atresia is the most common indication for childhood liver
      transplantation. The effects of successful portoenterostomy (PE) on native liver
      histology remain unclear. AIMS: We assessed changes in native liver histology
      after a successful PE in relation to liver function and clinical outcomes.
      METHODS: In total, 70 native liver biopsies of 44 biliary atresia patients were
      obtained at PE (n=30), 4.2 years after successful PE (n=23) and 1.1 years after
      failed PE (n=17), and reviewed for cholestasis, fibrosis, inflammation, and
      cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor
      livers served as controls. RESULTS: After a successful PE [serum bilirubin 11 (2
      to 35) MUmol/L at biopsy], histologic native liver cholestasis completely
      resolved in 83% of the patients and portal inflammation significantly decreased.
      Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct
      proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining
      [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects,
      respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of
      the patients, associated with the presence of portal hypertension, and correlated
      with serum-conjugated bilirubin (r=0.601, P=0.002), bile duct proliferation
      (r=0.657, P=0.001), and CK7 positivity (r=0.657, P=0.001). Aspartate transferase
      to platelet ratio index predicted native liver fibrosis and development of
      esophageal varices. The degree of fibrosis and portal inflammation at PE were
      unrelated to native liver survival. CONCLUSIONS: Despite resolution of
      cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7
      immunostaining, and fibrosis persist after successful PE. Fibrosis is associated
      with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity
      (chronic cholestasis), and development of portal hypertension.

PMID- 24275706
TI  - The fate of inhaled (14)C-labeled PCB11 and its metabolites in vivo.
AB  - BACKGROUND: The production ban of polychlorinated biphenyl (PCB) technical
      mixtures has left the erroneous impression that PCBs exist only as legacy
      pollutants. Some lower-chlorinated PCBs are still being produced and contaminate
      both indoor and ambient air. OBJECTIVES: To inform PCB risk assessment, we
      characterized lung uptake, distribution, metabolism and excretion of PCB11 as a
      signature compound for these airborne non-legacy PCBs. METHODS: After delivering
      [(14)C]PCB11 to the lungs of male rats, radioactivity in 34 major tissues and 5
      digestive matter compartments was measured at 12, 25, 50, 100, 200 and 720min
      postexposure, during which time the excreta and exhaled air were also collected.
      [(14)C]PCB11 and metabolites in lung, liver, blood, digestive matter, urine,
      feces, and adipose tissues were extracted separately to establish the metabolic
      profile of the disposition. RESULTS: [(14)C]PCB11 was distributed rapidly to all
      tissues after 99.8% pulmonary uptake and quickly underwent extensive metabolism.
      The major tissue deposition of [(14)C]PCB11 and metabolites translocated from
      liver, blood and muscle to skin and adipose tissue 200min postexposure, while
      over 50% of administered dose was discharged via urine and feces within 12h.
      Elimination of the [(14)C]PCB11 and metabolites consisted of an initial fast
      phase (t1/2=9-33min) and a slower clearance phase to low concentrations. Phase II
      metabolites dominated in liver blood and excreta after 25min postexposure.
      CONCLUSIONS: This study shows that PCB11 is completely absorbed after inhalation
      exposure and is rapidly eliminated from most tissues. Phase II metabolites
      dominated with a slower elimination rate than the PCB11 or phase I metabolites
      and thus can best serve as urine biomarkers of exposure.

PMID- 24275709
TI  - Video capsule endoscopy after bariatric and gastric surgery: oral ingestion is
      associated with satisfactory completion rate.
AB  - GOALS: To investigate the outcomes of video capsule endoscopy (VCE) performed on
      patients after bariatric and gastric surgery with a focus on delivery method
      (oral ingestion or endoscopic placement). BACKGROUND: There is minimal published
      data regarding the use of VCE in patients after bariatric and gastric surgery and
      the optimal delivery method is unknown. METHODS: Retrospective case series of
      patients with bariatric or gastric surgery undergoing VCE in a tertiary care
      center over 3 years. Outcomes of interest were completion of the procedure and
      bowel transit times. RESULTS: Twenty-three patients met study criteria. They
      underwent 24 VCE in the study period, with 13/16 (81.3%; 95% CI, 54%-96%)
      completed to the colon after oral ingestion and 5/8 (62.5%; 95% CI, 24%-91%)
      completed after endoscopic deployment. The median gastric transit time after oral
      ingestion was <1 minute (IQR, <1 to 99). Median total transit time after oral
      ingestion was 291 minutes (IQR, 213 to 434) and after endoscopic deployment was
      364 minutes (IQR, 233 to >440) (P=0.48). There were no instances of capsule
      retention. CONCLUSIONS: Oral ingestion of VCE resulted in a satisfactory
      completion rate with rapid gastric transit after bariatric and gastric surgery.
      There were no capsule retention events. Given this and the favorable risk and
      cost profile, oral ingestion should be favored over endoscopic placement in this
      patient population.

PMID- 24275710
TI  - Alpha-fetoprotein testing is still necessary for the detection of small
      hepatocellular carcinomas.

PMID- 24275711
TI  - The prevalence of elevated alanine transaminase and its possible causes in the
      general Korean population.
AB  - GOALS: The goal of the study was to investigate the current prevalence and causes
      of elevated alanine transaminase (ALT) in the general Korean population.
      BACKGROUND: Incidentally elevated ALT is frequently found because of increasing
      access to hospitals and blood tests. STUDY: A population-based cross-sectional
      study was carried out based on the Fourth Korean National Health and Nutrition
      Examination Survey (K-NHANES). Eligible subjects included 7894 men and 10,197
      women. We defined elevated ALT as >43 U/L. Among the subjects with elevated ALT,
      those who consumed alcohol, had the hepatitis B surface antigen (HBsAg), were
      obese (body mass index >=25 kg/m), were insulin resistant (the homeostasis model
      assessment-insulin resistance), or had metabolic syndrome (MetS) were
      investigated. RESULTS: The prevalence of elevated ALT was 7.4% in the Korean
      population. Increased ALT was more common in men (11.6%) than in women (3.1%)
      (P<0.001). Subjects with hypertension, diabetes, dyslipidemia (cholesterol >=240
      mg/dL or triglycerides >=150 mg/dL), obesity, significant consumption of alcohol,
      HBsAg positive, or MetS were associated with elevated ALT (all P<0.001). The most
      common potential cause of elevated ALT was metabolic disorder (MetS, obesity,
      and/or insulin resistance), which comprised 74.9% of cases. MetS was found in
      42.7% of men and 49.7% of women (P=0.031). Excess alcohol drinking was found in
      29.6% of men and 7.5% of women with elevated ALT (P<0.001). HBsAg positivity was
      found in only 6% of subjects. CONCLUSIONS: Incidentally elevated ALT is common in
      the Korean population. It is associated with metabolic disorders (obesity,
      insulin resistance, or MetS) in the majority of patients. This finding suggests
      that nonalcoholic fatty liver disease might be the most common cause of elevated
      ALT in the general Korean population.

PMID- 24275712
TI  - A modified ribavirin-free interferon therapy with boceprevir in post-liver
      transplant recurrent hepatitis C.

PMID- 24275713
TI  - Covered self-expanding metal stents may be preferable to plastic stents in the
      treatment of chronic pancreatitis-related biliary strictures: a systematic review
      comparing 2 methods of stent therapy in benign biliary strictures.
AB  - BACKGROUND: Covered self-expanding metal stents (CSEMS) are being increasingly
      used in the endoscopic treatment of benign biliary strictures (BBS). There is no
      solid evidence yet to support their routine use. GOALS: To evaluate feasibility,
      success rate, and complications of CSEMS compared with multiple plastic stents
      (PS) in BBS in a systematic review. STUDY: A systematic search of electronic
      databases (Medline, Scopus, and Embase) for studies published from 2000 to 2012
      combined to hand-search of reference lists resulted 4977 articles. Out of 99
      potentially relevant studies selected for full-text review, 12 CSEMS (376
      patients) and 13 PS studies (570 patients) met the final inclusion criteria. A
      systematic review comparing the 2 methods was made using proportion meta
      analysis. RESULTS: A tendency to successful use of CSEMS in strictures related to
      chronic pancreatitis (CP) was shown: clinical success of 77% and 33% [95%
      confidence interval (CI), 61%-94% vs. 4%-63%, P=0.06] was achieved with CSEMS and
      PS at 12 months follow-up, respectively. There were no differences in the success
      rates of other etiologies except CP or in the early complications. In CSEMS,
      incidence of late adverse events was lower in CP-related strictures (3% vs. 67%,
      95% CI, 0%-13% vs. 17%-99%, P=0.02). The median number of endoscopic retrograde
      cholangiopancreatographies was lower with CSEMSs: 1.5 versus 3.9 (P=0.002).
      CONCLUSIONS: Improved clinical success with fewer endoscopic sessions and
      corresponding complication rate may be achieved with CSEMS treatment compared
      with PS in BBS secondary to CP. In other BBS etiologies, this systematic review
      remains inconclusive.

PMID- 24275715
TI  - Early colon screening of adult patients with cystic fibrosis reveals high
      incidence of adenomatous colon polyps.
AB  - BACKGROUND AND GOALS: Cystic fibrosis (CF) is associated with increased incidence
      of gastrointestinal cancer. Increasing overall life expectancy of CF patients
      predicts emergence of colon cancer as a significant clinical problem in the adult
      CF population. The primary aim of this study was to estimate the incidence of
      adenomatous colon polyps in patients with CF during systematic screening by
      colonoscopy. STUDY: This is a single-center series of 45 CF patients aged 40
      years and above (mean age, 47 y) undergoing colonoscopic screening. A fraction of
      these patients (9/45) had history of organ transplantation. Results from
      transplant and nontransplant patients were analyzed separately. RESULTS: Adult CF
      patients have a high incidence of adenomatous polyps identified by colonoscopy.
      In addition, positive examinations are characterized by multiple polyps and
      common features of advanced pathology. The incidence of adenomatous colon polyps
      is greater in male patients, although the 1 patient in this cohort found to have
      colorectal cancer was female. CONCLUSIONS: CF has features of a hereditary colon
      cancer syndrome. Increasing life expectancy of CF patients suggests that earlier
      colon screening in this population may be warranted. Optimal criteria for
      initiation of screening and frequency of surveillance should be subject of
      further studies.

PMID- 24275714
TI  - Dysbiosis of gut fungal microbiota is associated with mucosal inflammation in
      Crohn's disease.
AB  - GOALS: We aim to characterize the fungal microbiota in the intestinal mucosa and
      feces in patients with Crohn's disease (CD). BACKGROUND: Fungi represent a
      diverse microbial community in the human intestine and might play a role in the
      pathogenesis of CD; however, little is known about the structure and composition
      of the fungal microbiota especially adhering to the intestinal mucosa in CD
      patient. STUDY: Nineteen patients with active CD and 7 healthy individuals were
      recruited in this study. The mucosa-associated and fecal fungal microbiotas in CD
      patients were analyzed using culture-independent community fingerprint
      techniques. RESULTS: The fungal richness and diversity were significantly
      elevated in the inflamed mucosa compared with the noninflamed mucosa. The
      predominant fungal composition in the inflamed mucosa was strikingly altered,
      mainly characterized by expansion in the proportions of Candida spp., Gibberella
      moniliformis, Alternaria brassicicola, and Cryptococcus neoformans. The fecal
      fungal community was perturbed in CD patients as accompanied by increased fungal
      diversity and prevalence in Candida albicans, Aspergillus clavatus, and C.
      neoformans. The species richness and diversity of the mucosal fungal community
      were associated with the expression of TNF-alpha, IFN-gamma, or IL-10 (P<0.05).
      The diversity of the fecal fungal microbiota positively correlated with serum C
      reactive protein and CD activity index (P<0.05). CONCLUSIONS: This study first
      demonstrates that the fungal microbiota in the inflamed mucosa is distinguishable
      from that of the noninflamed area. Shifts of gut fungal microbiota composition
      may be associated with mucosal inflammation and disease activity of CD. Our data
      would provide novel insights into understanding the potential of gut fungal
      microbiota in the pathogenesis of CD.

PMID- 24275716
TI  - Impact of ethnicity in upper gastrointestinal hemorrhage.
AB  - GOALS: To examine ethnicity's role in the etiology and outcome of upper
      gastrointestinal hemorrhage (UGIH). BACKGROUND: UGIH is a serious condition with
      considerable associated morbidity and mortality. MATERIALS AND METHODS: We
      analyzed 2196 patients admitted with acute UGIH between January 2006 and February
      2012. Complete clinical data were gathered prospectively and entered into our GI
      Bleed Registry, which captures demographic and clinical variables. Results were
      analyzed using the chi2 analyses and the analysis of variance techniques with
      Tukey multiple comparisons. RESULTS: Among 2196 patients, 620 (28%) were black,
      625 (29%) white, 881 (40%) Hispanic, and 70 (3%) were members of other
      ethnicities. Gastroduodenal ulcers (25%), esophageal varices (25%), and
      esophagitis (12%) were the most frequently identified causes of UGIH. Blacks
      experienced a high rate of gastroduodenal ulcers (199/620), whereas Hispanics
      most commonly had esophageal varices. In all ethnicities, the most common cause
      of bleeding in patients younger than 35 or older than 65 years was gastroduodenal
      ulcer disease. However, among patients aged 35 to 64 years, there were
      differences in the etiology of UGIH. Blacks aged 50 to 64 years frequently
      experienced gastroduodenal ulcers, whereas Hispanics aged 35 to 49 years
      typically had esophageal varices. Rebleeding rates were significantly lower in
      whites (5.8%) than in Hispanics (9.9%) or blacks (8.7%) (P=0.02). CONCLUSIONS: By
      examining a diverse population, we conclude that UGIH may follow trends.
      Hispanics were likely to have esophageal varices and higher rebleeding rates,
      whereas blacks were likely to have ulcers and the highest mortality. Whites were
      equally likely to have ulcers or varices, but a lower rate of rebleeding.

PMID- 24275717
TI  - The effect of puerperal uterine disease on uterine involution in cows assessed by
      Doppler sonography of the uterine arteries.
AB  - The objective of this study was to investigate the effects of puerperal uterine
      disease on uterine blood flow using trans-rectal Doppler sonography. Lactating
      Holstein Friesian cows (n=44) were divided into two groups based on whether they
      were healthy (UD-; n=23) or had uterine disease (UD+; n=21) defined as retained
      fetal membranes and/or metritis. General clinical examination, vaginoscopy, trans
      rectal palpation, and trans-rectal B-Mode sonography were conducted on Days 8,
      11, 18, 25 and then every 10 days until Day 65 after calving. Doppler sonography
      of the uterine arteries was conducted on Day 8, during diestrus after the second
      ovulation (Days 40-60 after calving) and during diestrus before breeding (Days 63
      75 after calving). Cows with uterine disease had greater (P<0.05) uterine size as
      assessed trans-rectally compared with cows of the UD group. Sonographic
      measurements on Day 11 after parturition revealed a greater (P<0.05) horn
      diameter in cows of the UD+ than in the UD- group. Both uterine size and uterine
      horn diameter decreased more earlier following parturition (P<0.05) in cows of
      the UD- group. Blood flow volume (BFV) was greater and pulsatility index was less
      on Day 8 after calving in cows of UD+ than UD- group (P<0.05). In cows of the UD
      , but not in those of the UD+ group, there was a further reduction in BFV
      subsequent to Day 45 after calving (P<0.05). The results of this study show that
      uterine blood flow measures by trans-rectal Doppler sonography are affected by
      puerperal uterine disease. 

PMID- 24275718
TI  - Is chemically synthesized graphene 'really' a unique substrate for SERS and
      fluorescence quenching?
AB  - We demonstrate observation of Raman signals of different analytes adsorbed on
      carbonaceous materials, such as, chemically reduced graphene, graphene oxide
      (GO), multi-walled carbon nanotube (MWCNT), graphite and activated carbon. The
      analytes selected for the study were Rhodamine 6G (R6G) (in resonant conditions),
      Rhodamine B (RB), Nile blue (NBA), Crystal Violet (CV) and acetaminophen
      (paracetamol). All the analytes except paracetamol absorb and fluoresce in the
      visible region. In this article we provide experimental evidence of the fact that
      observation of Raman signals of analytes on such carbonaceous materials are more
      due to resonance effect, suppression of fluorescence and efficient adsorption and
      that this property in not unique to graphene or nanotubes but prevalent for
      various type of carbon materials. 

PMID- 24275719
TI  - On testing factorial invariance: A reply to J.C.F. de Winter.
AB  - Since its publication, the Driver Behavior Questionnaire (DBQ) has been used for
      comparing subgroups of respondents on the constructs formed through factor
      analyzing the questionnaire items. However, not enough attention has been paid to
      ascertaining that the instrument actually measures the same constructs in the
      same way in all respondent groups. I recently published an article (Mattsson,
      2012) that aimed to do this for the Finnish 28-item version of the DBQ using the
      stage-wise factorial invariance approach in the Exploratory Structural Equation
      Modeling (ESEM) context. de Winter (2013) commented on the publication, arguing
      that the results were artifacts due to measurement error that too many factors
      were extracted and that too strict criteria for invariance were applied. In this
      contribution, I reply to each criticism and suggest methodological approaches for
      ensuring the measurement invariance of self-report instruments such as the DBQ. 

PMID- 24275720
TI  - Micro-simulation of vehicle conflicts involving right-turn vehicles at signalized
      intersections based on cellular automata.
AB  - At intersection, vehicles coming from different directions conflict with each
      other. Improper geometric design and signal settings at signalized intersection
      will increase occurrence of conflicts between road users and results in a
      reduction of the safety level. This study established a cellular automata (CA)
      model to simulate vehicular interactions involving right-turn vehicles (as
      similar to left-turn vehicles in US). Through various simulation scenarios for
      four case cross-intersections, the relationships between conflict occurrences
      involving right-turn vehicles with traffic volume and right-turn movement control
      strategies are analyzed. Impacts of traffic volume, permissive right-turn
      compared to red-amber-green (RAG) arrow, shared straight-through and right-turn
      lane as well as signal setting are estimated from simulation results. The
      simulation model is found to be able to provide reasonable assessment of
      conflicts through comparison of existed simulation approach and observed
      accidents. Through the proposed approach, prediction models for occurrences and
      severity of vehicle conflicts can be developed for various geometric layouts and
      traffic control strategies. 

PMID- 24275721
TI  - Genetics of dizziness: cerebellar and vestibular disorders.
AB  - PURPOSE OF REVIEW: Recent advances in next generation sequencing techniques (NGS)
      are increasing the number of novel genes associated with cerebellar and
      vestibular disorders. We have summarized clinical and molecular genetics findings
      in neuro-otolology during the last 2 years. RECENT FINDINGS: Whole-exome and
      targeted sequencing have defined the genetic basis of dizziness including new
      genes causing ataxia: GBA2, TGM6, ANO10 and SYT14. Novel mutations in KCNA1 and
      CACNA1A genes are associated with episodic ataxia type 1 and type 2,
      respectively. Moreover, new variants in genes such as COCH, MYO7A and POU4F3 are
      associated with nonsyndromic deafness and vestibular dysfunction. Several
      susceptibility loci have been linked to familial vestibular migraine, suggesting
      genetic heterogeneity, but no specific gene has been identified. Finally, loci
      for complex and heterogeneous diseases such as bilateral vestibular hypofunction
      or familial Meniere disease have not been identified yet, despite their strong
      familial aggregation. SUMMARY: Cerebellar and vestibular disorders leading to
      dizziness or episodic vertigo may show overlapping clinical features. A deep
      phenotyping including a complete familial history is a key step in performing a
      reliable molecular genetic diagnosis using NGS. Personalized molecular medicine
      will be essential to understand disease mechanisms as well as to improve their
      diagnosis and treatment.

PMID- 24275722
TI  - The ischemic penumbra: the location rather than the volume of recovery determines
      outcome.
AB  - PURPOSE OF REVIEW: The clinical efficiency of thrombolysis is explained by the
      rescue of ischemic penumbra areas resulting from early arterial recanalization.
      The perfusion-diffusion weighted imaging mismatch is a commonly used MRI
      surrogate of the ischemic penumbra. However, the randomized trials testing the
      mismatch hypothesis have been negative. We will review the 'mismatch concept' and
      the recent studies that aim to localize the clinically eloquent areas of penumbra
      in middle cerebral artery (MCA) infarcts. RECENT FINDINGS: New methods of image
      analysis have shown that poor outcomes after MCA stroke are related to infarction
      of an extremely well localized area of the periventricular white matter and
      adjacent internal capsule, where projections and association tracts are crossing
      and converging. This area almost colocalizes with the area salvaged by early
      arterial recanalization and is located extremely close to the initial ischemic
      core. SUMMARY: The location of the area that correlates with disability in MCA
      stroke patients and that is salvaged by early arterial recanalization is in the
      same specific region of the deep white matter, close to the initial ischemic
      core. These findings may have important implications for designing new
      recanalization trials and support the importance of basic research on white
      matter neuroprotection.

PMID- 24275723
TI  - Anomalously increased oxygen reduction reaction activity with accelerated
      durability test cycles for platinum on thiolated carbon nanotubes.
AB  - We report an anomalous phenomenon in Pt supported on thiolated multi-walled
      carbon nanotubes (Pt-S-MWNT): oxygen reduction reaction (ORR) activity increases
      with accelerated durability test (ADT) cycles. Sub-nanometer-sized Pt clusters on
      S-MWNT were gradually agglomerated to an optimal size with ADT cycles, and
      finally showed increased ORR activity after the ADT. 

PMID- 24275725
TI  - The etiology of infectious proctitis in men who have sex with men differs
      according to HIV status.
AB  - We compared the spectrum of pathogens responsible for infectious proctitis
      between HIV-positive and HIV-negative men who have sex with men. Only 32% of men
      with herpes simplex virus (HSV)-associated proctitis had visible external anal
      ulceration.The etiology of infectious proctitis among HIV-positive and HIV
      negative men is as follows: chlamydia (23.4% vs. 21.7%, P = 0.7), gonorrhea
      (13.4% vs. 10.8%, P = 0.5), HSV-1 (14.2% vs. 6.5%, P = 0.04), HSV-2 (22% vs.
      12.3%, P = 0.03), lymphogranuloma venereum (7.8% vs. 0.7%, P = 0.004), and
      multiple infections (17.7% vs. 8.6%, P = 0.017). Thirty-two percent with HSV
      proctitis had external anal ulceration. 

PMID- 24275726
TI  - Sexual coercion and sexual violence at first intercourse associated with sexually
      transmitted infections.
AB  - BACKGROUND: Violence against women has been associated with subsequent risky
      sexual behaviors and sexually transmitted infections (STIs). We explored whether
      sexual coercion or violence at first intercourse was associated with self
      reported STIs. METHODS: Using nationally representative data from the 2006 to
      2010 National Survey of Family Growth, we analyzed female respondents aged 18 to
      44 (n = 9466) who answered questions on coercion at first intercourse
      (wantedness, voluntariness, and types of force used) and STIs using logistic
      regression analyses. We explored degrees of coercion, which we label as neither,
      sexual coercion (unwanted or nonphysical force), or sexual violence (involuntary
      or physical force). RESULTS: Eighteen percent of US women reported sexual
      coercion, and 8.4% experienced sexual violence at first intercourse. Compared
      with women who experienced neither, the odds of reporting an STI was
      significantly greater for women who experienced sexual coercion (odds ratio,
      1.27; 95% confidence interval, 1.01-1.60), after controlling for all variables.
      The association between sexual violence at first intercourse and STIs (odds
      ratio, 1.20; 95% confidence interval, 0.91-1.57) seemed to be attenuated by
      subsequent sexual violence. CONCLUSIONS: Understanding that women who reported a
      variety of coercive sexual experiences are more likely to have contracted an STI
      may indicate a need to focus on the broader continuum of sexual violence to fully
      understand the impact of even subtle forms of violence on women's health. In
      addition, focusing on subsequent sexual behaviors and other negative consequences
      remains important to improve the sexual health of women who have experienced
      coercive sexual intercourse.

PMID- 24275724
TI  - Pelvic inflammatory disease: identifying research gaps--proceedings of a workshop
      sponsored by Department of Health and Human Services/National Institutes of
      Health/National Institute of Allergy and Infectious Diseases, November 3-4, 2011.
AB  - In November 2011, the National Institutes of Health convened a workshop of basic
      researchers, epidemiologists, and clinical experts in pelvic inflammatory disease
      to identify research gaps hindering advances in diagnosis, treatment, and
      prevention. This article summarizes the presentations, discussions, and
      conclusions of this group and highlights significant controversies that reveal
      aspects of pelvic inflammatory disease research that would most greatly benefit
      from the application of newer molecular, immunologic, and radiologic techniques.
      Multiple limitations to performing new clinical trials exist; however, emerging
      data from ongoing clinical trials will add to the current body of knowledge
      regarding prevention and treatment strategies. In addition, use of established
      health care databases could serve as a valuable tool for performance of unbiased
      epidemiologic outcome studies. 

PMID- 24275728
TI  - Identifying the correlates of membership in HIV-serodiscordant partnerships in
      New York City.
AB  - BACKGROUND: Identification and characterization of patients in HIV-serodiscordant
      partnerships can inform strategies to improve HIV prevention efforts for this
      group. METHODS: We conducted a case-control analysis using New York City
      Department of Health and Mental Hygiene HIV surveillance and partner services
      (PS) data from July 2006 to July 2010. HIV-infected index patients reported and
      interviewed for PS who named 1 or more sex and/or syringe-sharing partner (n =
      1309) and their sex partners notified by New York City Department of Health and
      Mental Hygiene with confirmed HIV serostatus (n = 1564) were selected for
      analysis. Index patients were classified into either serodiscordant or
      seroconcordant-positive partnerships based on the HIV serostatus of their
      partner(s). Multivariable regression analysis was conducted to examine the
      likelihood of membership in a serodiscordant partnership by a range of individual
      and partnership-level variables. RESULTS: Of the 1309 index patients, 624 (48%)
      were in HIV-serodiscordant partnerships. In multivariable analysis, the
      likelihood of serodiscordant partnership membership was slightly higher among
      women, individuals with unknown HIV transmission risk, and those with 2 to 3
      named partners versus 1. Index patients claimed more partners than they named;
      for example, index patients who named 1 partner claimed an average of 2.3
      partners in the past 12 months. CONCLUSIONS: Many HIV-infected patients who
      received PS were in HIV-serodiscordant partnerships, with characteristics
      indicating potential for HIV transmission. Our findings suggest several potential
      programmatic and policy needs, including enhanced linkage-to-care efforts for
      this population, especially HIV-infected individuals with uncontrolled viremia;
      ongoing PS for individuals with evidence of continuing exposure of others; and
      participation by patients and their serodiscordant, steady partners in local
      prevention interventions.

PMID- 24275727
TI  - Cost-effectiveness of screening men in Maricopa County jails for chlamydia and
      gonorrhea to avert infections in women.
AB  - BACKGROUND: Chlamydia and gonorrhea infections can lead to serious and costly
      sequelae in women, but sequelae in men are rare. In accordance with the Centers
      for Disease Control and Prevention guidelines, female jail inmates in Maricopa
      County (Phoenix area), Arizona, are screened for these infections. Owing to lack
      of evidence of screening benefits in men, male inmates are tested and treated
      based on symptoms only. METHODS: We developed a probabilistic simulation model to
      simulate chlamydia and gonorrhea infections in Maricopa County jail male inmates
      and transmissions to female partners per year. We estimated the cost
      effectiveness of screening as the cost per infection averted. Costs were
      estimated from the perspective of the Maricopa County Department of Public Health
      and the Correctional Health Services. RESULTS: Compared with symptom-based
      testing and treating strategy, screening male arrestees of all ages and only
      those 35 years or younger yielded the following results: averted approximately
      556 and 491 cases of infection in women at a cost of approximately US $1240 and
      $860 per case averted, respectively, if screened during physical examination
      (between days 8 and 14 from entry to jail), and averted approximately 1100 and
      995 cases of infections averted at a cost of US $1030 and $710 per infection
      averted, respectively, if screened early, within 2 to 3 days from entry to jail.
      CONCLUSIONS: Screening of male inmates incurs a modest cost per infection averted
      in women compared with symptom-based testing. Screening in correctional settings
      can be used by public health programs to reduce disease burden, sequelae, and
      associated costs.

PMID- 24275729
TI  - A case of late-stage lymphogranuloma venereum in a woman in Europe.
AB  - Lymphogranuloma venereum is caused by Chlamydia trachomatis serovars L1-L3. The
      third stage of the disease leads to chronic progressive lymphangitis. The first
      European case of elephantiasic enlargement of the female genitalia caused by C.
      trachomatis L2 serovar in decades is reported. 

PMID- 24275730
TI  - Declining prevalence rates of syphilis among police officers in Guinea-Bissau,
      West Africa, 1990-2010.
AB  - We analyzed prevalence rates of syphilis (positive Treponema pallidum
      hemagglutinin antigen/T. pallidum particle antigen and venereal disease research
      laboratory test) among police officers in Guinea-Bissau from 1990 to 2010 and
      found a significant decline from 4.5% to 0.4% (P = 0.0065). Our results are in
      line with other recent reports from West Africa. More research is needed to
      identify the reasons for this decline. 

PMID- 24275731
TI  - Unprotected casual sex equally common with local and Western partners among long
      term Dutch travelers to (sub)tropical countries.
AB  - We studied casual sexual partnerships and consistency of condom use among Dutch
      long-term, travelers to (sub)tropical regions. Forty-two percent of casual sexual
      partnerships (n = 192/462) were with local partners, of which 39% were
      unprotected. Fewer travelers to Sub-Saharan Africa had casual sex, but partner's
      ethnicity was not significant in predicting condom use. 

PMID- 24275732
TI  - Sex workers' noncommercial male partners who inject drugs report higher-risk
      sexual behaviors.
AB  - Female sex workers are less likely to use condoms with noncommercial male
      partners than clients. We compare noncommercial male partners who do and do not
      inject drugs in Tijuana and Ciudad Juarez, Mexico. Sexual risk behaviors were
      more prevalent among injectors, who could promote HIV/sexually transmitted
      infection transmission in this region. 

PMID- 24275733
TI  - Prevalence and factors associated with Trichomonas vaginalis infection among high
      risk women in Los Angeles.
AB  - Remnant specimen from 1215 women screening for chlamydia/gonorrhea at 4 different
      venue types (sexually transmitted disease clinics, home-test kit users, juvenile
      and adult detention) in Los Angeles, California, were tested for Trichomonas
      vaginalis. Prevalence of T. vaginalis varied by screening population, and
      concurrent chlamydia or gonorrhea was independently associated with T. vaginalis.

PMID- 24275734
TI  - Elevated cerebrospinal fluid interleukin-17A and interferon-gamma levels in early
      asymptomatic neurosyphilis.
AB  - BACKGROUND: The mechanisms underlying the process of Treponema pallidum clearance
      from the central nervous system have not yet been established. Considering that
      neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with
      a lymphocytic predominance, it has been suggested that cells involved in the
      adaptive immune response may play a role in this process. In the current study,
      we assessed the cytokine production profile of T-helper cells in the serum and
      CSF of patients with early syphilis, with and without CSF abnormalities. METHODS:
      Cerebrospinal fluid and blood samples were collected from 33 patients with
      secondary and early latent syphilis. Five patients (15%) had a reactive CSF
      Venereal Disease Research Laboratory test without any accompanying neurological
      symptoms. According to the Centers of Disease Control and Prevention
      classification, they were diagnosed with asymptomatic neurosyphilis. Serum and
      CSF levels of interferon-gamma (IFN-gamma; Th1-type cytokine), interleukin-4 (IL
      4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were
      determined by enzyme-linked immunosorbent assay. RESULTS: Patients with
      asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and
      IFN-gamma (7.8-fold) in the CSF compared with patients in the no-neurosyphilis
      group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease
      Research Laboratory test result (presumptive neurosyphilis group). In this group,
      CSF IFN-gamma and CSF IL-17A levels were also significantly elevated when
      compared with no-neurosyphilis group. There was no correlation between serum and
      CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with
      both CSF IL-17A (r = 0.4, P = 0.01) and IFN-gamma (r = 0.42, P = 0.01).
      CONCLUSIONS: Increased CSF levels of IFN-gamma and IL-17A in syphilitic patients
      with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper
      cells producing IFN-gamma and IL-17) may contribute to the inflammatory response
      associated with neurosyphilis. In addition, the lack of correlation between serum
      and CSF IL-17A levels suggests intrathecal production of this cytokine. Further
      studies are needed to establish the exact nature of the immune response
      accompanying neurosyphilis and its clinical significance.

PMID- 24275735
TI  - Gestational and congenital syphilis epidemic in the Colombian Pacific Coast.
AB  - BACKGROUND: Congenital syphilis (CS) is a major global public health problem.
      Buenaventura, a socioeconomically deprived municipality in the Colombian Pacific
      Coast, accounts for 6.6% of all CS cases in Colombia. To begin to understand the
      main reasons for the high rates of the disease in Buenaventura, we conducted a
      retrospective electronic health record analysis of all infants admitted with CS
      during the first 7 months of 2011 to the Hospital Departamental de Buenaventura,
      the city's main birthing hospital. METHODS: The diagnosis of gestational syphilis
      and CS was based on a predefined Colombian public health service algorithm.
      Clinical, laboratory, and sociodemographic parameters for all infants studied,
      including maternal access to prenatal care, syphilis serologic diagnosis, and
      adequacy of penicillin treatment, were abstracted and analyzed. RESULTS: A total
      of 89 infants met the case definition for CS. Most mothers (80%) were affiliated
      with government-regulated or private health care insurance plans. While 64 (70%)
      of 92 attended at least 1 antenatal care visit and 59 of these 64 (84%) were
      screened for syphilis, only 5 (8%) of 59 received appropriate antibiotic therapy.
      Although most infants were asymptomatic at birth, prematurity (15/82) was common.
      Two infants died in the neonatal period, and 5 pregnancies ended in stillbirth.
      CONCLUSIONS: Our findings confirm that Buenaventura has a very high incidence of
      CS and demonstrate that existing antenatal care gestational syphilis programs are
      flawed. Prevention strategies should emphasize enhanced early syphilis screening
      in pregnancy, preferably through the implementation of point-of-care testing in
      the community and same-day treatment with at least 1 dose of penicillin.

PMID- 24275737
TI  - Parents' and sons' beliefs in sexual disinhibition after human papillomavirus
      vaccination.
AB  - BACKGROUND: The concern that adolescent girls who receive human papillomavirus
      (HPV) vaccine may be more likely to have sex (ie, sexual disinhibition) has been
      commonplace in media coverage, but this belief is not held by many parents of
      adolescent girls. Because no studies have addressed this topic for adolescent
      boys, we examined parents' and their adolescent sons' beliefs in sexual
      disinhibition occurring after boys receive HPV vaccine. METHODS: A national
      sample of parents of adolescent boys (n = 547) and their sons (aged 15-17 years;
      n = 176) completed online surveys in fall 2010. We used multi-item scales to
      measure parents' and sons' beliefs in sexual disinhibition after HPV vaccination.
      We used multivariate linear regression to identify correlates of beliefs in
      sexual disinhibition. RESULTS: Less than a quarter of parents or sons agreed with
      statements suggesting that HPV vaccination leads to sexual disinhibition among
      adolescent boys (range, 20%-24%). Parents who had more liberal political
      affiliations (beta = -0.11), had a daughter who had received HPV vaccine (beta = 
      0.12), or had no daughter (beta = -0.10) reported weaker beliefs in sexual
      disinhibition. Parents who reported higher anticipated regret if their sons got
      HPV vaccine and fainted (beta = 0.18) indicated stronger beliefs in sexual
      disinhibition. Sons who perceived higher peer acceptance of HPV vaccination (beta
      = 0.44) or were Hispanic (beta = 0.21) had stronger beliefs in sexual
      disinhibition. CONCLUSIONS: Most parents and sons did not believe that HPV
      vaccination leads to sexual disinhibition among boys. Understanding the
      characteristics of parents and sons who hold these beliefs may help inform
      efforts to increase HPV vaccine uptake among boys.

PMID- 24275738
TI  - Corynebacterium propinquum associated with acute, nongonococcal urethritis.
AB  - Corynebacterium propinquum is usually considered part of the normal human
      oropharyngeal flora and is rarely responsible for clinical infection. We report
      here what seems to be the first case of acute purulent urethral discharge in a
      young Iranian man with urethritis acquired after orogenital contact. Attention
      should be devoted to less common nondiphtheriae Corynebacterium species for
      differential diagnosis. 

PMID- 24275739
TI  - Obesity: The need to eat--overruling the homeostatic control of feeding.

PMID- 24275736
TI  - Increasing access by priority populations to Australian sexual health clinics.
AB  - Data from a network of 35 Australian sexual health clinics, in geographically
      diverse locations, showed that the number and proportion of patients from
      priority populations (ie, young people, men who have sex with men, indigenous
      people, and female sex workers) increased significantly between 2004 and 2011. 

PMID- 24275740
TI  - Pharmacotherapy: Small-molecule disruptors of glucokinase inhibition.

PMID- 24275741
TI  - Puberty in 2013: Unravelling the mystery of puberty.
AB  - In 2013, considerable progress was made towards deciphering the molecular
      foundations of puberty. Loss of transcriptional repression was identified as a
      core mechanism underlying the onset of puberty, and this loss was found to be
      precipitated by epigenetic cues. It was also discovered that nutritional
      deprivation delays puberty by repressing reproductive neuroendocrine function.

PMID- 24275745
TI  - Genetics: Mutant prolactin receptor--when lock and key no longer fit.

PMID- 24275746
TI  - Reproductive endocrinology: Menstrual dysfunction--a proxy for insulin resistance
      in PCOS?

PMID- 24275748
TI  - Characterization of early autophagy signaling by quantitative phosphoproteomics.
AB  - Under conditions of nutrient shortage autophagy is the primary cellular mechanism
      ensuring availability of substrates for continuous biosynthesis. Subjecting cells
      to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR
      signaling pathway triggering increased autophagic flux. To elucidate the
      regulation of early signaling events upon autophagy induction, we applied
      quantitative phosphoproteomics characterizing the temporal phosphorylation
      dynamics after starvation and rapamycin treatment. We obtained a comprehensive
      atlas of phosphorylation kinetics within the first 30 min upon induction of
      autophagy with both treatments affecting widely different cellular processes. The
      identification of dynamic phosphorylation already after 2 min demonstrates that
      the earliest events in autophagy signaling occur rapidly after induction. The
      data was subjected to extensive bioinformatics analysis revealing regulated
      phosphorylation sites on proteins involved in a wide range of cellular processes
      and an impact of the treatments on the kinome. To approach the potential function
      of the identified phosphorylation sites we performed a screen for MAP1LC3
      interacting proteins and identified a group of binding partners exhibiting
      dynamic phosphorylation patterns. The data presented here provide a valuable
      resource on phosphorylation events underlying early autophagy induction. 

PMID- 24275749
TI  - Evidence for a vortex-glass transition in superconducting Ba(Fe0.9Co0.1)2As2.
AB  - Measurements of magneto-resistivity and magnetic susceptibility were performed on
      single crystals of superconducting Ba(Fe0.9Co0.1)2As2 close to the conditions of
      optimal doping. The high quality of the investigated samples allows us to reveal
      dynamic scaling behaviour associated with a vortex-glass phase transition in the
      limit of a weak degree of quenched disorder. Accordingly, the dissipative
      component of the ac susceptibility is reproduced well within the framework of
      Havriliak-Negami relaxation, assuming a critical power-law divergence for the
      characteristic correlation time tau of the vortex dynamics. Remarkably, the
      random disorder introduced by the Fe1-xCox chemical substitution is found to act
      on the vortices as a much weaker quenched disorder than previously reported for
      cuprate superconductors such as Y1-xPrxBa2Cu3O7-delta. 

PMID- 24275750
TI  - Overexpression, purification, and enthalpy of unfolding of ferricytochrome c552
      from a psychrophilic microorganism.
AB  - The psychrophilic, hydrocarbonoclastic microorganism Colwellia psychrerythraea is
      important in global nutrient cycling and bioremediation. In order to investigate
      how this organism can live so efficiently at low temperatures (~4 degrees C),
      thermal denaturation studies of a small electron transfer protein from Colwellia
      were performed. Colwellia cytochrome c552 was overexpressed in Escherichia coli,
      isolated, purified, and characterized by UV-visible absorption spectroscopy. The
      melting temperature (Tm) and the van't Hoff enthalpy (DeltaHvH) were determined.
      These values suggest an unexpectedly high stability for this psychrophilic
      cytochrome.

PMID- 24275751
TI  - Sex-specific chest pain characteristics in the early diagnosis of acute
      myocardial infarction.
AB  - IMPORTANCE: Whether sex-specific chest pain characteristics (CPCs) would allow
      physicians in the emergency department to differentiate women with acute
      myocardial infarction (AMI) from women with other causes of acute chest pain more
      accurately remains unknown. OBJECTIVE To improve the management of suspected AMI
      in women by exploring sex-specific CPCs. DESIGN, SETTING, AND PARTICIPANTS: From
      April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients
      (796 women and 1679 men) presenting with acute chest pain to 9 emergency
      departments in a prospective multicenter study. The final diagnosis of AMI was
      adjudicated by 2 independent cardiologists. INTERVENTIONS: Treatment of AMI in
      the emergency department. MAIN OUTCOMES AND MEASURES: Sex-specific diagnostic
      performance of 34 predefined and uniformly recorded CPCs in the early diagnosis
      of AMI. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis
      in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with
      similar frequency in women and men, several CPCs were reported more frequently in
      women (P < .05). The accuracy of most CPCs in the diagnosis of AMI was low in
      women and men, with likelihood ratios close to 1. Thirty-one of 34 CPCs (91.2%)
      showed similar likelihood ratios for the diagnosis of AMI in women and men, and
      only 3 CPCs (8.8%) seemed to have a sex-specific diagnostic performance with P <
      .05 for interaction. These CPCs were related to pain duration (2-30 and >30
      minutes) and dynamics (decreasing pain intensity). However, because their
      likelihood ratios were close to 1, the 3 CPCs did not seem clinically helpful.
      Similar results were obtained when examining combinations of CPCs (all
      interactions, P >= .05). CONCLUSIONS AND RELEVANCE: Differences in the sex
      specific diagnostic performance of CPCs are small and do not seem to support the
      use of women-specific CPCs in the early diagnosis of AMI. TRIAL REGISTRATION
      clinicaltrials.gov Identifier: NCT00470587.

PMID- 24275752
TI  - Factors associated with calcification in the pedal arteries in patients with
      diabetes and neuropathy admitted for foot disease and its clinical significance.
AB  - The aim of this study was to determine the factors associated with calcification
      in the pedal arteries (CPAs) in a population of patients with diabetes admitted
      for acute foot disease and to find whether the presence of CPAs had any influence
      on the short-term outcomes. Electronic charts were retrospectively reviewed for
      patients admitted to our department for acute diabetic foot problems between
      January 1, 2008, and December 31, 2012. Digital images of the plain x-rays, which
      were performed on patients during this period, were reviewed. Patients were
      classified into 2 groups: those with absence (group 1) and presence of CPAs
      (group 2). One hundred and sixty-five patients were included in the present
      study. Ninety-eight (59.4%) patients had CPAs in the plain x-rays. The predictive
      variables related to the presence of CPAs were duration of diabetes >20 years
      (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.0-4.3), retinopathy (OR
      = 2.2, 95% CI = 1.0-4.6), albuminuria (OR = 3.3, 95% CI = 1.5-7.4), and
      peripheral arterial disease (OR = 4.2, 95% CI = 2.0-8.7). Fifty-six patients
      underwent amputation (33.9%): 13 (19.4%) in group 1 and 43 (43.9%) in group 2 (P
      < .01). Thirty-four patients (20.6) required reoperation: 6 (9%) in group 1 and
      28 (28.6%) in group 2 (P < .01). In conclusion, the predictive variables related
      to the presence of CPAs in a series of patients admitted for foot disease were
      duration of diabetes >20 years, retinopathy, albuminuria, and peripheral arterial
      disease. Differences in the outcomes were related to the association of CPAs with
      peripheral arterial disease. 

PMID- 24275753
TI  - Effect of radiofrequency ablation on healing of infected full-thickness wounds in
      minipigs.
AB  - The success of debridement is critical to optimize the treatment outcomes of
      traumatic wounds. To investigate the impact of radiofrequency ablation on healing
      potential of infected wounds, minipigs with infected full-thickness skin defects
      on backs were divided into 4 treatment groups randomly: radiofrequency ablation
      debridement, electric knife debridement, sharp instrument debridement, and no
      treatment. The healing rate, healing time, tissue filling rate, bacterial
      quantitative, and histological assay were evaluated postoperatively. The results
      obtained provide evidence that the wounds after radiofrequency ablation treatment
      enhanced the skin wound-healing efficacy and had better outcomes of tissue
      filling compared with other debridement therapies. Furthermore, we quantified the
      bacterial counting level in wound samples, and the results revealed a more
      significant decreasing trend in radiofrequency ablation group than that of the
      electric knife debridement group and the sharp instrument debridement group.
      Postoperative histological measurements showed that there were better granulation
      formation and re-epithelialization and collagen deposition in radiofrequency
      ablation-treated wounds than those in other groups. The present findings
      demonstrate that radiofrequency ablation has a significantly influence on
      reducing the number of bacteria and improving the healing quality and is a
      promising candidate for treatment of infected wounds. 

PMID- 24275754
TI  - A minimally invasive modified reverse sural adipofascial flap for treating
      posttraumatic distal tibial and calcaneal osteomyelitis.
AB  - Our aim was to report a modified reverse sural adipofascial flap for treating
      posttraumatic distal tibial or calcaneal osteomyelitis. We retrospectively
      reviewed the records of 15 patients with posttraumatic distal tibial or calcaneal
      osteomyelitis treated with modified reverse sural adipofascial flaps between 2005
      and 2010. The flap was raised through 2 short incisions in the posterior aspect
      of the lower leg. The raw surface of the flap was covered with a full-thickness
      skin graft. Donor sites were closed primarily. Lower Extremity Functional Scale
      (LEFS) scores and 2-point discrimination (TPD) were recorded preoperatively and
      postoperatively. There were 12 males and 3 females, with an average age of 39
      years (range = 18-55 years). Twelve lesions were in the distal tibia and 3 in the
      calcaneus. The flap ranged in size from 11 * 5 cm to 16 * 7 cm. All flaps
      survived, and skin grafts healed without complications. Recipient sites had an
      anatomic contour, and all patients were able to ambulate without the assistance
      of special shoes or orthoses. No infections recurred, and no ulcers of the
      grafted skin occurred with the regular wearing of shoes. The follow-up duration
      was 18.7 +/- 6.8 months (range = 12-36 months). The mean LEFS score increased
      from 22.4 +/- 8.3 preoperatively to 53.0 +/- 11.2 postoperatively (P = .001). TPD
      markedly recovered at 24 months postoperatively. The modified reverse sural
      adipofascial flap provides good outcomes in treating distal tibial and calcaneal
      osteomyelitis with minimal donor site morbidity. 

PMID- 24275755
TI  - Citric acid treatment of chronic nonhealing ulcerated tophaceous gout with
      bursitis.
AB  - The ulceration associated with gout tophi is very difficult to treat because of
      impaired and halted local inflammatory response resulting from the gout treatment
      regimen. We report chronic nonhealing tophaceous gout with bursitis in an 80-year
      old male, not responding to conventional treatment modality for months together.
      This nonhealing ulcer was treated successfully with local application of 3%
      citric acid ointment for 22 days. 

PMID- 24275757
TI  - New insights about cross-reactive epitopes of six trypanosomatid genera revealed
      that Crithidia and Leptomonas have antigenic similarity to L. (L.) chagasi.
AB  - We investigated whether ELISA using crude antigens from insect and plant
      trypanosomatids, which are non-pathogenic and easily cultivated in large scale,
      has the same positivity data as Leishmania (Leishmania) chagasi, the etiological
      agent of human visceral leishmaniasis (VL) or canine leishmaniasis (CanL), or as
      Trypanosoma cruzi, the etiological agent of Chagas disease (CD). The antigens
      from Crithidia fasciculata, Crithidia luciliae, and Leptomonas seymouri showed
      100% cross-reactivity with VL and CanL samples, with no statistically titers
      differences from L. (L.) chagasi, however, 34% (17/50) of VL samples revealed
      higher titers using the insect trypanosomatids than the homologous antigen. On
      the other hand, antigens from Strigomonas culicis, Angomonas deanei, and
      Phytomonas serpens showed low cross-reactivity with VL and CanL samples. The sera
      from patients with American tegumentary leishmaniasis showed low levels of cross
      reactivity with all trypanosomatids investigated, even with L. (L) chagasi,
      without titers dissimilarity among them. These parasites were also worthless as
      antigen source for detection of CD cases, which required homologous antigens to
      reach 100% positivity. This study showed, by ELISA, that crude extract of
      Crithidia and Leptomonas have epitopes similar to L. (L.) chagasi, which supports
      the idea of using them as antigens source for the serodiagnosis of visceral
      leishmaniasis. 

PMID- 24275756
TI  - Bone marrow cell mobilization by the systemic use of granulocyte colony
      stimulating factor (GCSF) improves wound bed preparation.
AB  - Innovative approaches are needed to accelerate the healing of human chronic
      wounds not responding to conventional therapies. An evolving and promising
      treatment is the use of stem cells. Our group has previously described the use of
      expanded (in vitro) autologous stem cells aspirated from human bone marrow and
      applied topically in a fibrin spray to human acute and chronic wounds. More
      recently, we have sought ways to mobilize stem cells directly from the bone
      marrow, without in vitro expansion. In this report, we show that systemic
      injections of granulocyte colony-stimulating factor (GCSF) can mobilize stem
      cells from bone marrow into the peripheral blood and then to the wound site. Our
      objectives were to optimize parameters for this method by using mouse models and
      proof of principle in a human chronic wound situation. Mice were injected for 5
      days with 2 different formulations of GCSF and compared to control saline. To
      monitor stem cell mobilization, flow cytometric measurements of Sca-1 and c-Kit
      and colony-forming cell assays were performed. Full-thickness tail wounds in mice
      were created and monitored for healing, and polyvinyl alcohol sponges were
      implanted dorsally to assess collagen accumulation. To determine bone marrow stem
      cell homing to the wound site, chimeric mice transplanted with Green Fluorescent
      Protein bone marrow cells were scanned by live imaging. Additionally, as proof of
      principle, we tested the systemic GCSF approach in a patient with a nonhealing
      venous ulcer. Our findings lay the ground work and indicate that the systemic
      administration of GCSF is effective in mobilizing bone marrow stem cells into the
      peripheral blood and to the wound site. These findings are associated with an
      increased accumulation of collagen and promising results in terms of wound bed
      preparation and healing. 

PMID- 24275758
TI  - Scholarship or censorship.

PMID- 24275759
TI  - Artificial ligament reconstruction of sternoclavicular joint instability: report
      of a novel surgical technique with early results.
AB  - Symptomatic instability of the sternoclavicular (SC) joint is an uncommon
      problem. The majority of patients respond well to nonoperative measures, although
      a small number require reconstructive surgery for symptomatic instability, with
      varying surgical techniques reported in the literature. We report a series of 5
      operations (in 4 patients) with chronic SC joint instability treated by
      reconstruction of SC and costoclavicular ligaments using an artificial ligament
      weave (LARS: Ligament Augmentation and Reconstruction System). Preoperative and
      postoperative disabilities of the Arm, Shoulder, and Hand (DASH) Scores and
      Oxford Shoulder Scores were collected to evaluate the outcomes. The patients had
      a mean age of 20 years (range, 17 to 22 y), with 2 male and 2 female patients.
      Three of the patients had traumatic dislocation of the SCJ and 1 patient had
      bilateral symptomatic atraumatic instability. Anterior instability was observed
      in 4 joints and posterior instability in 1 joint. In all cases, reconstruction
      was achieved with a 30 mm LARS ligament. Postoperative follow-up was for an
      average of 29 months (range, 19 to 41 mo). The DASH Score improved from 51.7
      points (range, 24.2 to 75.0) preoperatively to 13.7 points (range, 8.3 to 20.8)
      postoperatively. The Oxford Shoulder Scores improved from 20.6 preoperatively
      (range, 15 to 32) to 41.8 postoperatively (range, 39 to 47). All patients
      returned to full activity including competitive sports. In conclusion,
      stabilization of the SC joint using a LARS ligament with a weave technique is a
      feasible option for young, active patients with symptomatic SC joint instability
      after failure of nonoperative treatment. 

PMID- 24275760
TI  - Volar plate fixation of recalcitrant scaphoid nonunions with volar carpal artery
      vascularized bone graft.
AB  - Chronic scaphoid fracture nonunion continues to present a significant challenge
      to the treating orthopedic surgeon. Internal fixation with threaded compression
      screws leads to high union rates, and is currently the gold standard, but there
      are certainly circumstances where a scaphoid screw does not provide the stability
      necessary for nonunion repair. Results using a volar buttress plate have been
      promising, but have not been described in conjunction with the use of
      vascularized bone graft. Vascularized bone grafts have been shown to be highly
      effective in achieving rapid and reproducible rates of union. We describe a novel
      combination of a vascularized volar distal radius wedge autograft pedicled on the
      volar carpal artery and volar buttress plating for salvage treatment of chronic
      scaphoid nonunion. 

PMID- 24275761
TI  - The "turtleneck" pulley plasty for finger flexor tendon repair.
AB  - Injuries to the flexor tendons are frequent. Even when correctly treated, they
      can cause a loss of mobility of the digits secondary to postoperative adhesions.
      Further, conflicts between the tendon suture and the pulleys can limit the range
      of motion of the tendon and the flexion of the fingers. We propose a new pulley
      plasty that permits immediate retraining and avoids conflict with the tendon
      suture. Ten patients underwent surgery for a tendon injury in zone II, with no
      lesions of the associated pedicles. The tendons were repaired by a 4-strand
      stitch technique associated with a continuous peritendinous suture. Pulley plasty
      was systematically performed on A2, A4, or both. Eight patients recovered a
      satisfactory range of motion with a finger to palm distance of <1 cm, and 2
      others with a distance of <2 cm. Two tenolyses were performed, for which no
      secondary reconstruction of the pulleys was necessary. This plasty technique is
      simple to carry out, reliable, and reproducible. Because it facilitates tendon
      repair and reinforces the existing pulleys, it permits immediate retraining and
      controlled active mobilization. 

PMID- 24275762
TI  - Immunosuppression and monitoring of rejection in hand transplantation.
AB  - Advances in vascularized composite allotransplantation over the last decade have
      achieved significant milestones in basic science and translational research, as
      well as clinically with highly encouraging functional and immunologic outcomes.
      However, certain immunologic challenges remain. In particular, although tolerance
      has been induced to nearly all components of a hand allograft in experimental
      models, the skin component may still be subject to acute rejection episodes.
      Currently, conventional immunosuppressive protocols have been successful at
      preventing allograft loss; however, they have not prevented episodes of acute
      skin rejection. Furthermore, the profound side effect profile of the life-long,
      high-dose, multidrug immunosuppression regimen that is necessary to maintain a
      viable graft alters the risk to benefit ratio of this non-life-saving procedure.
      Therefore, there must be a concerted effort in the scientific community to
      develop novel protocols to either minimize immunosuppression or to induce
      tolerance to the allograft to promote the widespread application of this life
      changing procedure. 

PMID- 24275763
TI  - Benefits of an ungual prosthesis in traumatology and reconstructive surgery of
      the nail.
AB  - Lesions of the nail apparatus can leave esthetic and sometimes functional
      sequelae. Many sequelae are the result of incorrect growth of the nail plate.
      During the acute phase, in the absence of a nail plate, the nail bed may
      keratinize or form a pyogenic granuloma, compromising harmonious regrowth of the
      nail plate. The ideal is to reinsert the plate if it is available, but if it has
      been lost, an ungual prosthesis must be inserted to act as a temporary
      implantable splint. This implant must have the same shape and structure as the
      nail plate. Many ideas have been used in the past, including suture pack,
      infusion tubing, or x-ray film. However, these techniques are no longer
      acceptable, as, in many countries, all types of implants require a documented
      recorded identification or "traceability." The implants we use are packed
      individually in sterile packaging. They are therefore immediately available in
      traumatology departments treating Hand Emergencies. These prostheses are also
      very useful in reconstructive surgery of the digit in the hand and feet,
      particularly when the nail bed has to be reconstructed. In this case, the implant
      is used to flatten the nail bed, whether it is sutured, grafted, or reconstructed
      with flaps, during the slow regrowth of the nail plate. The author reports his
      experience in emergency or secondary repair of the nail complex. 

PMID- 24275764
TI  - Rehabilitation after bilateral hand transplantation in the quadrimembral patient:
      review and recommendations.
AB  - The hand transplantation is a unique entity in the fields of medicine and
      rehabilitation. Hand therapy and rehabilitation programs are consistently
      reported as essential to a successful functional outcome for the hand transplant
      patient. In September 2011, our medical center performed their first bilateral
      hand and forearm transplant on a 28-year-old female 4 years after losing her
      lower extremities and upper extremities due to multiorgan system failure and
      pressure-induced extremity ischemia. She participated in 4 months of hand
      therapy, occupational therapy, and physical therapy at our institution, and then
      returned to her hometown to continue with an intensive therapy program. At 16
      months after transplantation, she had sensory return to diminished protective
      level and motor return to all transplanted muscles except for intrinsics. Our
      hand therapy team established a treatment program based on literature,
      collaboration with other transplant centers, and clinical experience. Now, 2
      years after our first hand transplant case, we assess our plan and program, offer
      suggestions for developing a treatment program and encourage therapist to
      collaborate with their own transplant team and others around the United States
      and the world. 

PMID- 24275765
TI  - Above-elbow (supracondylar) arm transplantation: clinical considerations and
      surgical technique.
AB  - Vascularized composite allotransplantation, also known as "Reconstructive
      Transplantation" is becoming more commonplace worldwide. Hand and upper extremity
      transplantation make up the majority of clinical vascularized composite
      allotransplantation cases performed so far. As success with reconstructive
      transplantation becomes more common, more challenging examples of limb loss are
      being addressed, including above-elbow, or "supracondylar" upper extremity
      transplants. Although very few of these cases have been performed worldwide, the
      authors' experience includes the only 2 cases performed in the United States at
      the time of this report. This article will discuss indications, challenges,
      surgical technique, expected outcomes, and alternative technologies for treatment
      of limb loss above the elbow. 

PMID- 24275766
TI  - New single-stranded DNA virus with a unique genomic structure that infects marine
      diatom Chaetoceros setoensis.
AB  - Diatoms are among the most abundant organisms in nature; however, their
      relationships with single-stranded DNA (ssDNA) viruses have not yet been defined
      in detail. We report the isolation and characterisation of a virus (CsetDNAV)
      that lytically infects the bloom-forming diatom Chaetoceros setoensis. The virion
      is 33 nm in diameter and accumulates in the nucleus of its host. CsetDNAV
      harbours a covalently closed-circular ssDNA genome comprising 5836 nucleotides
      and eight different short-complementary fragments (67-145 nucleotides), which
      have not been reported in other diatom viruses. Phylogenetic analysis based on
      the putative replicase-related protein showed that CsetDNAV was not included in
      the monophyly of the recently established genus Bacilladnavirus. This discovery
      of CsetDNAV, which harbours a genome with a structure that is unique among known
      viruses that infect diatoms, suggests that other such undiscovered viruses
      possess diverse genomic architectures.

PMID- 24275767
TI  - Regulation of the sympathetic nervous system by the kidney.
AB  - PURPOSE OF REVIEW: The relationship between excessive sympathetic drive to the
      kidneys and hypertension is now well established. This has led to the development
      of therapeutic approaches, such as catheter-based bilateral renal denervation,
      for the treatment of resistant hypertension. The purpose of this article is to
      review the sympathetic regulation of kidney function, with specific focus given
      to clinical insights gained from human studies involving renal denervation and
      animal studies that have identified possible causal factors associated with
      disease. RECENT FINDINGS: Continuous chronic determinations of renal sympathetic
      nerve activity (RSNA) in animal models have recently identified a role of
      angiotensin II and obesity in the initiation of neurally related hypertension.
      Other potential mediating factors influencing RSNA include adipose tissue derived
      factors, neurohumoral pathways and baroreceptor-mediated mechanisms. Hypertension
      development is likely to reflect a combination of these factors. Interventions
      that directly interrupt renal sympathetic signaling show promising results in the
      treatment of resistant hypertension. SUMMARY: The mechanisms underlying the
      development of neurogenic hypertension are beginning to be elucidated, thanks to
      technological advancements that enable the direct measurement of RSNA.
      Determining factors associated with hypertension development will help to
      identify strategies to mitigate disease as well as provide scientific support for
      novel nonpharmacologic therapies.

PMID- 24275768
TI  - Heme oxygenase-1 and acute kidney injury.
AB  - PURPOSE OF REVIEW: Heme oxygenase activity, possessed by an inducible heme
      oxygenase-1 (HO-1) and a constitutive isoform (HO-2), catalyzes the conversion of
      heme to biliverdin, liberates iron, and generates carbon monoxide. First shown in
      acute kidney injury (AKI), HO-1 is now recognized as a protectant against diverse
      insults in assorted tissues. This review summarizes recent contributions to the
      field of HO-1 and AKI. RECENT FINDINGS: Recent findings elucidate the following:
      the transcriptional regulation and significance of human HO-1 in AKI; the
      protective effects of HO-1 in age-dependent and sepsis-related AKI, cardiorenal
      syndromes, and acute vascular rejection in renal xenografts; the role of heme
      oxygenase in tubuloglomerular feedback and renal resistance to injury; the basis
      for cytoprotection by HO-1; the protective properties of ferritin and carbon
      monoxide; HO-1 and the AKI-chronic kidney disease transition; HO-1 as a biomarker
      in AKI; the role of HO-1 in mediating the protective effects of specific
      cytokines, stem cells, and therapeutic agents in AKI; and HO-2 as a protectant in
      AKI. SUMMARY: Recent contributions support, and elucidate the basis for, the
      induction of HO-1 as a protectant against AKI. Translating such therapeutic
      potential into a therapeutic reality requires well tolerated and effective
      modalities for upregulating HO-1 and/or administering its products, which,
      optimally, should be salutary even when AKI is already established.

PMID- 24275769
TI  - Aldosterone's mechanism of action: roles of lysine-specific demethylase 1,
      caveolin and striatin.
AB  - PURPOSE OF REVIEW: Aldosterone's functions and mechanisms of action are different
      depending on the tissue and the environmental condition. The mineralocorticoid
      receptor is present in tissues beyond epithelial cells, including the heart and
      vessels. Furthermore, aldosterone has direct adverse effects by both genomic and
      rapid/nongenomic actions not only through a nuclear receptor but also through
      caveolae-mediated intracellular events. Also, multiple environmental-genetic
      interactions play an important role in salt-sensitive hypertension (SSH) and
      aldosterone modulation. These findings have reshaped our vision of aldosterone's
      role in cardiovascular pathophysiology. This review describes new mediators of
      aldosterone's mechanisms of action: lysine-specific demethylase 1 (LSD1),
      caveolin 1 (cav-1) and striatin. RECENT FINDINGS: LSD1, an epigenetic regulator,
      is involved in the pathogenesis of SSH in both humans and rodents. In addition,
      cav-1, the main component of caveolae, plays a substantial role in mediating
      aldosterone pathways of SSH. The mineralocorticoid receptor interacts with cav-1
      and is modulated by sodium intake. Finally, striatin, a scaffolding protein,
      mediates a novel interaction between signalling molecules and mineralocorticoid
      receptor's rapid effects in the cardiovascular system. SUMMARY: Substantial
      progress in aldosterone's functions and mechanisms of action should facilitate
      the study of cardiovascular diseases and the role of sodium intake in aldosterone
      induced damage.

PMID- 24275771
TI  - Patterns of cortico-limbic activations during visual processing of sad faces in
      depression patients: a coordinate-based meta-analysis.
AB  - The author retrieved 10 functional magnetic resonance imaging studies about
      visual tasks for emotional faces in subjects with depression. The activation foci
      were then summarized and entered into a coordinate-based meta-analysis. The
      depression group showed significantly increased activations in the left striatum
      and left parahippocampal gyrus; the control group showed increased activations in
      the left medial frontal gyrus, left middle frontal gyrus, right thalamus, left
      anterior cingulate, and superior frontal gyrus. The study suggests that
      depression patients have limbic activations, and controls have fronto-thalamic
      activations with visual processing of emotional faces. 

PMID- 24275770
TI  - Intrarenal renin-angiotensin system in regulation of glomerular function.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      current knowledge regarding the role of the intrarenal rennin-angiotensin system
      (RAS) in the regulation of glomerular function including glomerular dynamics and
      filtration rate, glomerular permeability and structural alterations during
      chronic increases in intrarenal angiotensin (Ang) II. RECENT FINDINGS: Recent
      studies have continued to delineate the complex interactions among the various
      RAS components that participate in regulating glomerular function. Although Ang
      II acting on AT1 receptors remains as the predominant influence on glomerular
      dynamics, some of these effects are indirectly mediated by Ang II modulating the
      sensitivity of the macula densa tubuloglomerular feedback mechanism as well as
      the more recently described feedback mechanism from the connecting tubule.
      Interestingly, the actions of Ang II on these systems cause opposite effects on
      glomerular function demonstrating the complexities associated with the influences
      of Ang II on glomerular function. When chronically elevated, Ang II also
      stimulates and/or interacts with other factors, including reactive oxygen
      species, cytokines and growth factors and other hormones or paracrine agents, to
      elicit structural alterations. SUMMARY: Recent studies have provided further
      evidence for the presence of many components of the RAS in glomerular structures,
      which supports the importance of locally produced angiotensin peptides to
      regulate glomerular haemodynamics, filtration rate and macromolecular
      permeability and contribute to fibrosis and glomerular injury when
      inappropriately augmented.

PMID- 24275772
TI  - Protamine-adsorbed magnetic nanoparticles for efficient isolation and
      concentration of hepatitis-C virus from human plasma samples.
AB  - Protamine hydrochloride adsorbed onto citrated superparamagnetic iron oxide
      nanoparticles represents an efficient tool for capturing and concentration of
      hepatitis-C virus from plasma samples, improving the sensitivity of downstream
      analysis by nucleic acid testing. 

PMID- 24275773
TI  - Modification of xenogeneic graft materials for improved release of P-15 peptides
      in a calvarium defect model.
AB  - Particulate bone augmentation is an established clinical alternative to
      regenerate bone. However, in regions of poor bone quality or previously infected
      sites, the clinical outcomes are more inconsistent. For that purpose, peptides
      have been added to particulate materials in an attempt to render them with
      antibacterial properties or to improve their osseoconductivity. For instance,
      competence-stimulating peptide (CSP) has been studied to decrease the division
      rate of Streptococcus mutans. Also, the addition of a specific short amino acid
      sequence peptide derived from type I collagen (P-15) to the bone substitutes has
      been introduced in an attempt to increase its osseoconductivity. The present
      study hypothesized that xenogeneic graft materials with and without CSP would
      present improved host-to-biomaterial response when used in combination with P-15.
      Particulate graft materials with and without P-15, OsteoGraf with CSP and
      OsteoGraf, were implanted in an 8-mm rabbit calvarial defect for 4 weeks, and
      thereafter, histological and histomorphometrical evaluation was performed. The
      results showed that both OsteoGraf and CSP groups with the addition of P-15
      induced bone growth towards the center of the defect. Furthermore, the addition
      of CSP to Osteograf showed a tendency to increase its osteoconductivity when
      combined with P-15. The results of the current study suggested that P-15 had some
      impact on osteogenesis; however, the effect differed between different bone
      substitute materials. Further investigation is necessary to clarify its
      effectiveness when used in combination with bone substitutes. 

PMID- 24275774
TI  - Hematological parameters in patients of cleft lip and cleft palate with special
      reference to eosinophil counts.
AB  - INTRODUCTION: Birth abnormalities like cleft lip and cleft palate account for
      about 1.4 per 1000 live births in India. These are seen to be associated with a
      high incidence of eosinophilia which delays the surgical management of these
      patients. AIMS: The aim of this paper is to study the hematological parameters in
      patients of cleft lip and cleft palate. PATIENTS AND METHODS: A total of 223
      cases of cleft lip and cleft palate were taken up for the study. Hematological
      parameters including hemoglobin, total leukocyte count, differential leukocyte
      count, absolute eosinophil count, and red cell indices were studied. RESULTS:
      Anemia was found in 182/223 (81.63%) cases which was most commonly of microcytic
      hypochromic type. Eosinophilia was seen in 46/223 (20.60%) cases. CONCLUSIONS:
      Many cleft lip and cleft palate patients show high eosinophil counts. Absolute
      eosinophil count was found to be a better parameter for assessment of
      eosinophils.

PMID- 24275775
TI  - Effects of mepivacaine 2% with epinephrine in the cardiovascular activity of
      patients undergoing third molar surgery: a prospective clinical study.
AB  - BACKGROUND: Cardiovascular effects of epinephrine, especially on blood pressure
      (BP) and heart rate (HR), have been well documented. When present in dental local
      anesthetic solutions, epinephrine concentration ranges from 5 to 20 ug/mL. Doses
      less than 200 ug are recommended to be clinically safe. OBJECTIVES: This study
      investigated the effects of the anesthetic solution of mepivacaine (2%) with
      epinephrine (10 ug/mL) in cardiovascular activity (HR and BP). METHODS: Twenty
      six patients underwent outpatient surgery for the removal of 2 unilateral (group
      I, n = 15) or 4 (group II, n = 11) third molars in a single session, being
      injected 5.4 and 10.8 mL of anesthetic solution, equivalent to 54 and 108 ug of
      epinephrine, respectively. The cardiovascular activity was monitored by
      cardioscope during the experimental period of 2 hours. Heart rate and BP were
      measured at the intervals of 0, 5, 10, 15, 20, 30, 40, 60, 90, and 120 minutes
      after anesthetic injection. RESULTS: After application of 2-way analysis of
      variance test, comparison between groups was not statistically significant for HR
      (P = 0.1388), systolic BP (P = 0.0228), and diastolic BP (P = 0.9846). However,
      patients from group II presented significantly greater sway in HR (P < 0.0001),
      systolic BP (P = 0.0169), and diastolic BP (P < 0.0001) in the course of 2 hours.
      CONCLUSIONS: Blood pressure did not present significant alterations after a local
      injection of 54 or 108 ug of epinephrine during surgery to remove 2 or 4 third
      molars. Although without significance, HR was more elevated in the 108-ug dose of
      epinephrine during the removal of 4 third molars.

PMID- 24275776
TI  - Intraoperative acquired pressure ulcer on lower lip: a complication of
      rhinoplasty.
AB  - Device-related pressure ulcers are not rare. However, few studies have reported
      pressure ulcers of the lower lip. We encountered 2 patients with an
      intraoperative pressure ulcer on the lower lip caused by an endotracheal tube
      during rhinoplasty. A 46-year-old man showed a deviated nose and nasal
      obstruction. Surgery was performed under general anesthesia with endotracheal
      intubation. The surgery time was 270 minutes. A 23-year-old man also showed a
      deviated nose and nasal obstruction. Surgery was performed under general
      anesthesia in the same fashion. The surgery time was 273 minutes. A preformed
      endotracheal tube was inserted and positioned over the mandible and secured with
      polyurethane film intraoperatively. Both patients had pressure ulcers on their
      lower lip. One showed a slightly visible scar. Care must be taken to avoid ulcers
      of the lower lip in rhinoplasty patients.

PMID- 24275777
TI  - Heminasal proboscis, a rare craniofacial cleft.
AB  - Craniofacial clefts are extremely rare congenital anomalies, the importance of
      which lies in their great range of variety of anatomic forms and their complex
      management. Proboscis is one of the rare cases of this kind in which half of the
      nose is separated from the face and it is only pedicled on the right or left
      medial canthal regions by a nose-like, rudimentary tubular structure. This
      article reports the case of a 3-month-old infant with left-sided proboscis. Left
      lower eyelid coloboma was also present. The proboscis was treated with local
      flaps at the age of 3 months, and at the age of 10 months the coloboma was
      managed. 

PMID- 24275778
TI  - Lateral orbital wall fracture as a mechanism of blow-out fracture in a patient
      with extensive pneumatization of the sphenoid bone.
AB  - We report a patient with a lateral orbital wall fracture that occurred as a
      result of a blow-out fracture. The patient has extensive pneumatization of the
      sphenoid sinus, and the air extends into the lateral orbital wall. It makes the
      lateral orbital wall much thinner unusually, being more vulnerable to a sudden
      increase in intraorbital pressure. Pure blow-out fracture of the lateral orbital
      wall has not been reported in the medical literature. Therefore, this is the
      first case report of a lateral orbital wall fracture occurring as a blow-out
      mechanism. 

PMID- 24275779
TI  - A rare remote epidural hematoma secondary to decompressive craniectomy.
AB  - Remote epidural hematoma (REDH) is an uncommon complication of decompressive
      craniectomy. Remote epidural hematomas of the parietal occiput region have been
      reported only rarely. We report a unique case of delayed-onset bilateral
      extensive straddle postsagittal sinus and bilateral lateral sinus parietal
      occiput REDH after decompressive craniectomy, of which volume was approximately
      130 mL, with left deviating midline structures. The patient was immediately taken
      back to the operating room for evacuation of the REDH via bilateral parietal and
      occiput craniectomy. Postoperatively, serial computed tomographic scans performed
      3 days later showed that the REDH had been completely evacuated. Two months
      later, the patient regained full consciousness and obtained a near-complete
      recovery except for right facial paralysis. 

PMID- 24275780
TI  - Middle ear pressure after septoplasty.
AB  - OBJECTIVES: The aim of this study was to determine the level of middle ear
      pressure and alterations in middle ear pressure levels after septoplasty among
      the individuals having advanced degree isolated nasal septal deviation. METHODS:
      A prospective randomized study was conducted. The study included 72 adult
      patients who had severely deviated septum. The middle ear pressure values at both
      sides of nasal obstruction and opposite side were determined using tympanometry
      before the surgery and at postoperative week 3. The middle ear pressure values
      were divided into 2 groups, side of nasal obstruction (group 1) and opposite
      nonaffected side (group 2). The middle ear pressure values obtained before and
      after septoplasty were compared. RESULTS: Before the septoplasty, the median
      middle ear pressure value was -54 dPa at the side of nasal obstruction, and -46
      dPa at the opposite side. Three weeks after the septoplasty, it was -38 dPa at
      the side of nasal obstruction, and -40 dPa at the opposite side. The middle ear
      pressure improved by approximately 30% at the side of nasal obstruction and by
      11% at the nonaffected side; a statistically significant decrease was found at
      the side of nasal obstruction (P < 0.05). CONCLUSIONS: In adult patients with
      isolated nasal septum deviation, the middle ear pressure is lower at the side of
      nasal obstruction, but it remains within reference ranges. An approximately 30%
      improvement occurs in the middle ear pressure after septoplasty.

PMID- 24275782
TI  - Aesthetic reconstruction of the postburn neck contracture with a preexpanded
      anterolateral thigh free flap.
AB  - INTRODUCTION: The release of wide burn contractures leads to defects that cannot
      be closed with local flaps. In these cases, tissue expansion of local tissues may
      be a solution. However, when local tissues are also burned, distant tissue
      transfer remains the only option. Tissue expanded anterolateral thigh (ALT) flaps
      can be a reasonable option. CASE: A 15-year-old boy with a cervical burn
      contracture had limited movement in the neck. The release of the contracture and
      removal of the scarred tissue resulted in a 22 * 18-cm neck defect. This was
      resurfaced with preexpanded anterolateral thigh perforator flap. RESULT: Three
      months postoperatively, the flap shrunk to the point that the underlying
      aesthetic anatomical landmarks such as the clavicle, sternal notch,
      sternocleidomastoid muscle, and thyroid cartilage were clearly visible. The
      reconstruction was both functionally and cosmetically excellent. CONCLUSION:
      Tissue expanded ALT can be a good option in wide burn contractures where local
      tissues are inadequate. The advantages are (1) large flaps can be prepared
      without any functional loss, (2) the expanded skin thins making it more
      cosmetically appropriate to resurface skin only defect, and (3) the donor area
      stays under the clothes during expansion period and is well tolerated by the
      patient.

PMID- 24275781
TI  - Orbital malign trichilemmal tumor with cerebral involvement.
AB  - Proliferating trichilemmal tumor is a rare encountered neoplasm. This neoplasm is
      usually benign, but it may be locally aggressive. To the best of our knowledge,
      magnetic resonance (MR) imaging features of cerebral involvement of this unusual
      neoplasm have not been described. We report the MR imaging findings of a case of
      malign proliferating trichilemmal tumor, with cerebral involvement. 

PMID- 24275783
TI  - Autophagy researchers.

PMID- 24275785
TI  - Stability of Recombinant Tissue Plasminogen Activator at -30  degrees C over One
      Year.
AB  - Recombinant tissue plasminogen activator (rt-PA) is used to restore patency and
      avoid inadvertent removal of peripheral and central venous catheters. rt-PA was
      reconstituted (1 mg/mL) then cryopreserved at -30  degrees C for 1, 2, 3, 6, 8,
      and 12 months and, then its stability was determined. After cryopreservation for
      one and two months, rt-PA kept more than 95% of its activity compared to standard
      samples, while cryopreservation for three months caused 8% loss of activity.
      However, after cryopreservation for six months or more, rt-PA retained only 87.5%
      or less activity compared to standard samples. Therefore, it is recommended that
      reconstituted rt-PA be cryopreserved at -30  degrees C for a maximum period of
      three months. 

PMID- 24275784
TI  - Strategies to modulate heritable epigenetic defects in cellular machinery:
      lessons from nature.
AB  - Natural epigenetic processes precisely orchestrate the intricate gene network by
      expressing and suppressing genes at the right place and time, thereby playing an
      essential role in maintaining the cellular homeostasis. Environment-mediated
      alteration of this natural epigenomic pattern causes abnormal cell behavior and
      shifts the cell from the normal to a diseased state, leading to certain cancers
      and neurodegenerative disorders. Unlike heritable diseases that are caused by the
      irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of
      epigenetic memory is also a major concern in the clinical translation of the
      Nobel Prize-winning discovery of induced pluripotent stem cell technology.
      Consequently, there is an increasing interest in the development of novel
      epigenetic switch-based therapeutic strategies that could potentially restore the
      heritable changes in epigenetically inherited disorders. Here we give a
      comprehensive overview of epigenetic inheritance and suggest the prospects of
      therapeutic gene modulation using epigenetic-based drugs, in particular histone
      deacetylase inhibitors. This review suggests that there is a need to develop
      therapeutic strategies that effectively mimic the natural environment and include
      the ways to modulate the gene expression at both the genetic and epigenetic
      levels. The development of tailor-made small molecules that could epigenetically
      alter DNA in a sequence-specific manner is a promising approach for restoring
      defects in an altered epigenome and may offer a sustainable solution to some
      unresolved clinical issues. 

PMID- 24275786
TI  - The potential role of cell penetrating peptides in the intracellular delivery of
      proteins for therapy of erythroid related disorders.
AB  - The erythroid related disorders (ERDs) represent a large group of hematological
      diseases, which in most cases are attributed either to the deficiency or
      malfunction of biosynthetic enzymes or oxygen transport proteins. Current
      treatments for these disorders include histo-compatible erythrocyte transfusions
      or allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy
      delivered via suitable viral vectors or genetically modified HSCs have been under
      way. Protein Transduction Domain (PTD) technology has allowed the production and
      intracellular delivery of recombinant therapeutic proteins, bearing Cell
      Penetrating Peptides (CPPs), into a variety of mammalian cells. Remarkable
      progress in the field of protein transduction leads to the development of novel
      protein therapeutics (CPP-mediated PTs) for the treatment of monogenetic and/or
      metabolic disorders. The "concept" developed in this paper is the intracellular
      protein delivery made possible via the PTD technology as a novel therapeutic
      intervention for treatment of ERDs. This can be achieved via four stages
      including: (i) the production of genetically engineered human CPP-mediated PT of
      interest, since the corresponding native protein either is missing or is mutated
      in the erythroid progenitor cell (ErPCs) or mature erythrocytes of patients; (ii)
      isolation of target cells from the peripheral blood of the selected patients;
      (iii) ex vivo transduction of cells with the CPP-mediated PT of interest; and
      (iv) re-administration of the successfully transduced cells back into the same
      patients. 

PMID- 24275787
TI  - A Potent (R)-alpha-bis-lipoyl Derivative Containing 8-Hydroxyquinoline Scaffold:
      Synthesis and Biological Evaluation of Its Neuroprotective Capabilities in SH
      SY5Y Human Neuroblastoma Cells.
AB  - A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA,
      5) was synthesized as a new multifunctional drug candidate with antioxidant,
      chelant, and neuroprotective properties for the treatment of neurodegenerative
      diseases. We have investigated the potential effectiveness of LA-HQ-LA against
      the cytotoxicity induced by 6-OHDA and H2O2 on human neuroblastoma SH-SY5Y cell
      line. Our outcomes showed that LA-HQ-LA resulted in significant neuroprotective
      and antioxidant effects against H2O2- and 6-OHDA-induced neurotoxicity in human
      neuroblastoma SH-SY5Y cells, as assessed by MTT assay. In particular, it showed
      potent neuroprotective effects against 6-OHDA in RA/PMA differentiated cells at
      all the tested concentrations. 

PMID- 24275788
TI  - Clevidipine for perioperative blood pressure control in infants and children.
AB  - Various pharmacologic agents have been used for perioperative BP control in
      pediatric patients, including sodium nitroprusside, nitroglycerin, beta
      adrenergic antagonists, fenoldopam, and calcium channel antagonists. Of the
      calcium antagonists, the majority of the clinical experience remains with the
      dihydropyridine nicardipine. Clevidipine is a short-acting, intravenous calcium
      channel antagonist of the dihydropyridine class. It undergoes rapid metabolism by
      non-specific blood and tissue esterases with a half-life of less than 1 minute.
      As a dihydropyridine, its cellular and end-organ effects parallel those of
      nicardipine. The clevidipine trials in the adult population have demonstrated
      efficacy in rapidly controlling BP in various clinical scenarios with a favorable
      adverse effect profile similar to nicardipine. Data from large clinical trials
      regarding the safety and efficacy of clevidipine in children is lacking. This
      manuscript aims to review the commonly used pharmacologic agents for
      perioperative BP control in children, discuss the role of calcium channel
      antagonists such as nicardipine, and outline the preliminary data regarding
      clevidipine in the pediatric population. 

PMID- 24275791
TI  - Liver: Key role for alphav integrins in myofibroblasts in liver fibrosis.

PMID- 24275792
TI  - Hepatitis C in 2013: HCV causes systemic disorders that can be cured.
AB  - Successful treatment with antivirals reduces the incidence of some extrahepatic
      manifestations of HCV. Thus, the advent of well-tolerated and highly potent
      antiviral regimens might enable extension of the indication for therapy to
      patients at risk of developing serious extrahepatic disorders, irrespective of
      the severity of the underlying liver disease.

PMID- 24275793
TI  - Emerging surgical therapies for faecal incontinence.
AB  - Faecal incontinence is a common condition and is associated with considerable
      morbidity and economic cost. The majority of patients are managed with
      conservative interventions. However, for those patients with severe or refractory
      incontinence, surgical treatment might be required. Over the past 20 years,
      numerous developments have been made in the surgical therapies available to treat
      such patients. These surgical therapies can be classified as techniques of
      neuromodulation, neosphincter creation (muscle or artificial) and injection
      therapy. Techniques of neuromodulation, particularly sacral nerve stimulation,
      have transformed the management of these patients with a minimally invasive
      procedure that offers good results and low morbidity. By contrast, neosphincter
      procedures are characterized by being more invasive and associated with
      considerable morbidity, although some patients will experience substantial
      improvements in their continence. Injection of bulking agents into the anal canal
      can improve symptoms and quality of life in patients with mild-to-moderate
      incontinence, and the use of autologous myoblasts might be a future therapy.
      Further research and development is required not only in terms of the devices and
      procedures, but also to identify which patients are likely to benefit most from
      such interventions. 

PMID- 24275794
TI  - Liver: Potential therapeutic role of osteopontin in alcoholic liver disease.

PMID- 24275796
TI  - Diuretics and diarrhea: a dangerous combination: a teachable moment.

PMID- 24275795
TI  - Photoinduced features of energy bandgap in quaternary Cu2CdGeS4 crystals.
AB  - The quaternary chalcogenide crystal Cu2CdGeS4 was studied both experimentally and
      theoretically in the present paper. Investigations of polarized fundamental
      absorption spectra demonstrated a high sensitivity to external light
      illumination. The photoinduced changes were studied using a cw 532 nm green laser
      with energy density about 0.4 J cm(-2). The spectral maximum of the photoinduced
      anisotropy was observed at spectral energies equal to about 1.4 eV (energy gap
      equal to about 1.85 eV) corresponding to maximal density of the intrinsic defect
      levels. Spectroscopic measurements were performed for polarized and unpolarized
      photoinducing laser light to separate the contribution of the intrinsic defect
      states from that of the pure states of the valence and conduction bands. To
      understand the origin of the observed photoinduced absorption near the
      fundamental edge, the benchmark first-principles calculations of the structural,
      electronic, optical and elastic properties of Cu2CdGeS4 were performed by the
      general gradient approximation (GGA) and local density approximation (LDA)
      methods. The calculated dielectric function and optical absorption spectra
      exhibit some anisotropic behavior (shift of the absorption maxima in different
      polarizations) within the 0.15-0.20 eV energy range not only near the absorption
      edge; optical anisotropy was also found for the deeper inter-band transition
      spectral range. Peculiar features of chemical bonds in Cu2CdGeS4 were revealed by
      studying the electron density distribution. Possible intrinsic defects are shown
      to affect the optical absorption spectra considerably. Pressure effects on the
      structural and electronic properties were modeled by optimizing the crystal
      structure and calculating all relevant properties at elevated hydrostatic
      pressure. The first estimations of the bulk modulus (69 GPa (GGA) or 91 GPa
      (LDA)) and its pressure derivative for Cu2CdGeS4 are also reported. 

PMID- 24275797
TI  - Brains of optimistic older adults respond less to fearful faces.
AB  - The authors examined the neural correlates of emotion processing and how they
      relate to individual differences in optimism among older adults. Brain response
      during processing of fearful faces was measured by functional magnetic resonance
      imaging in 16 older adults and was correlated with level of optimism. Greater
      optimism was associated with reduced activation in the fusiform gyrus and frontal
      regions, which may reflect decreased salience of negative emotional information
      or better emotion regulation among optimistic individuals. Relationships
      persisted after taking into account cortical thickness, amygdala volume, and
      resting perfusion. Findings have potential implications for the promotion of
      successful aging. 

PMID- 24275798
TI  - What is the full range of medical and surgical treatments available for patients
      with Eustachian tube dysfunction?
AB  - PURPOSE OF REVIEW: To present the current medical and surgical treatment options
      for Eustachian tube dysfunction. RECENT FINDINGS: Balloon dilation or
      microdebrider Eustachian tuboplasty are feasible treatment options for patients
      with refractory dilatory dysfunction as an alternative to tympanostomy tube
      placement. There is increasing evidence that repair of patulous Eustachian tubes
      by the insertion of a shim or fat graft reconstruction within the lumen of the
      Eustachian tube orifice may be effective. SUMMARY: In patients with Eustachian
      tube dysfunction that is refractory to medical management, newer surgical
      techniques may provide symptomatic relief with a reasonable duration. Continued
      basic science research into the cause of dysfunction, the mechanisms of benefit
      from intervention and long-term clinical outcomes are necessary.

PMID- 24275799
TI  - When and how should we treat biofilms in chronic sinusitis?
AB  - PURPOSE OF REVIEW: Biofilms have been observed on the sinus mucosa of patients
      with chronic rhinosinusitis and are associated with poor clinical outcomes after
      surgery. This article summarizes the recent studies which describe the efficacy
      of treating biofilms in chronic rhinosinusitis. RECENT FINDINGS: Biofilms are
      polymicrobial communities comprised of bacteria that tend to be more antibiotic
      resistant than when in planktonic forms. Antibiotic therapy against biofilms is
      usually associated with relapse following cessation of treatment and may also
      have an adverse effect on normal commensal microflora. Surfactants can improve
      clinical symptoms, but their use has been limited by side effects. Other
      treatment modalities that physically remove or disrupt biofilms, such as
      ultrasound, have shown some efficacy in small trials. The impact of surgery on
      biofilms has not been extensively investigated. SUMMARY: The nature of biofilms
      makes their removal difficult. No currently available treatment directed against
      them has demonstrated lasting efficacy.

PMID- 24275800
TI  - What is new and promising with drug-eluting stents in sinus surgery?
AB  - PURPOSE OF REVIEW: In the surgical management of chronic rhinosinusitis, medical
      therapy is often used to prevent postoperative complications such as adhesions.
      These complications often require painful debridements in the clinic or revision
      surgery. Systemic steroids are not without risk and topical steroids are not
      ideal, as the duration of mucosal contact and exact dosage are unknown and
      penetration into gravity-dependent sinuses is suboptimal. Therefore, we reviewed
      the literature assessing the use of drug-eluting stents in the management of
      chronic rhinosinusitis. RECENT FINDINGS: Three randomized controlled trials and a
      meta-analysis support the efficacy and safety of the use of steroid-eluting
      implants in chronic rhinosinusitis. Implants placed in the ethmoid sinuses at the
      time of surgery have been found to significantly reduce postoperative adhesions,
      recurrence of polyposis, middle turbinate lateralization, the need for
      postoperative oral steroids and the need for postoperative interventions. Studies
      also support the ocular safety of steroid-eluting implants. SUMMARY: Steroid
      eluting implants are well tolerated and an effective addition to the
      armamentarium utilized in the management of chronic rhinosinusitis. Future
      developments for the use of drug-eluting implants in chronic rhinosinusitis are
      discussed.

PMID- 24275801
TI  - A prototype point-of-use assay for measuring heavy metal contamination in water
      using time as a quantitative readout.
AB  - This Communication describes a prototype quantitative paper-based assay that
      simultaneously measures the levels of Pb(2+) and Hg(2+) in water. The assay
      requires only measurements of time to yield a quantitative readout, and the
      results are independent of sample volume, humidity, and sample viscosity. 

PMID- 24275802
TI  - Diffusion-weighted magnetic resonance imaging for assessment of lung lesions:
      repeatability of the apparent diffusion coefficient measurement.
AB  - PURPOSE: To establish repeatability of apparent diffusion coefficients (ADCs)
      acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW
      MRI) in malignant lung lesions and investigate effects of lesion size, location
      and respiratory motion. METHODS: Thirty-six malignant lung lesions (eight
      patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted
      and axial single-shot echo-planar DW-MRI (b = 100, 500, 800 s/mm(2)) during free
      breathing. Regions of interest around target lesions on computed b = 800 s/mm(2)
      images by two independent observers yielded ADC values from maps (pixel-by-pixel
      fitting using all b values and a mono-exponential decay model). Intra- and inter
      observer repeatability was assessed per lesion, per patient and by lesion size (>
      or <2 cm) or location. RESULTS: ADCs were similar between observers (mean +/- SD,
      1.15 +/- 0.28 * 10(-3) mm(2)/s, observer 1; 1.15 +/- 0.29 * 10(-3) mm(2)/s,
      observer 2). Intra-observer coefficients of variation of the mean [median] ADC
      per lesion and per patient were 11% [11.4%], 5.7% [5.7%] for observer 1 and 9.2%
      [9.5%], 3.9% [4.7%] for observer 2 respectively; inter-observer values were 8.9%
      [9.3%] (per lesion) and 3.0% [3.7%] (per patient). Inter-observer coefficient of
      variation (CoV) was greater for lesions <2 cm (n = 20) compared with >2 cm (n =
      16) (10.8% vs 6.5% ADCmean, 11.3% vs 6.7% ADCmedian) and for mid (n = 14) vs
      apical (n = 9) or lower zone (n = 13) lesions (13.9%, 2.7%, 3.8% respectively
      ADCmean; 14.2%, 2.8%, 4.7% respectively ADCmedian). CONCLUSION: Free-breathing DW
      MRI of whole lung achieves good intra- and inter-observer repeatability of ADC
      measurements in malignant lung tumours. KEY POINTS: * Diffusion-weighted MRI of
      the lung can be satisfactorily acquired during free-breathing * DW-MRI
      demonstrates high contrast between primary and metastatic lesions and normal lung
      * Apparent diffusion coefficient (ADC) measurements in lung tumours are
      repeatable and reliable * ADC offers potential in assessing response in lung
      metastases in clinical trials.

PMID- 24275803
TI  - Using R2* values to evaluate brain tumours on magnetic resonance imaging:
      preliminary results.
AB  - OBJECTIVE: To determine the usefulness of the R2* value in assessing the
      histopathological grade of glioma at magnetic resonance imaging and
      differentiating various brain tumours. METHODS: Sixty-four patients with brain
      tumours underwent R2* mapping and diffusion-weighted imaging examinations. ANOVA
      was performed to analyse R2* values among four groups of glioma and among high
      grade gliomas (grades III and IV), low-grade gliomas (grades I and II),
      meningiomas, and brain metastasis. Spearman's correlation coefficients were used
      to determine the relationships between the R2* values or apparent diffusion
      coefficient (ADC) and the histopathological grade of gliomas. R2* values of low-
      and high-grade gliomas were analysed with the receiver-operator characteristic
      curve. RESULTS: R2* values were significantly different among high-grade gliomas,
      low-grade gliomas, meningiomas, and brain metastasis, but not between grade I and
      grade II or between grade III and grade IV. The R2* value (18.73) of high-grade
      gliomas provided a very high sensitivity and specificity for differentiating low
      grade gliomas. A strong correlation existed between the R2* value and the
      pathological grade of gliomas. CONCLUSIONS: R2* mapping is a useful sequence for
      determining grade of gliomas and in distinguishing benign from malignant tumours.
      R2* values are better than ADC for characterising gliomas. KEY POINTS: * Magnetic
      resonance imaging parameters are increasingly used to assess cerebral lesions. *
      R2* values are better than diffusion weighting for characterising gliomas. * R2*
      values can help distinguish among different grades of glioma. * Significant
      difference existed in R2* values between high- and low-grade gliomas.

PMID- 24275804
TI  - Can a structured questionnaire identify patients with reduced renal function?
AB  - OBJECTIVES: To evaluate a structured questionnaire in identifying outpatients
      with renal dysfunction before MRI or CT in various age groups. METHODS: All
      patients completed a questionnaire with five risk factors indicating renal
      dysfunction: renal disease, renal surgery, hypertension, gout and diabetes. Serum
      creatinine determined by the point-of-care (POC) technique and estimated
      glomerular filtration (eGFR) rate was calculated using CKD-EPI equation. RESULTS:
      A total of 1,467 patients were enrolled. Thirty-four patients (2%) had an eGFR
      <30 ml/min/1.73 m(2) and 123 (8%) had an eGFR <45 ml/min/1.73 m(2). Among 55% of
      the 1,467 patients reporting at least one risk factor, 30 (4%) had an eGFR <30
      ml/min/1.73 m(2) and 105 (13%) had an eGFR <45 ml/min/1.73 m(2). Among 651
      patients not reporting a risk factor, 4 (0.6%) had an eGFR <30 ml/min/1.73 m(2)
      and 18 (3%) had an eGFR <45 ml/min/1.73 m(2). All four patients were >70 years
      old, and 12 of the 18 patients were >70 years old. CONCLUSION: The questionnaire
      used in patients <70 years old and determination of eGFR in patients >70 years
      old identified all patients with an eGFR between 30 and 45 ml/min/1.73 m(2)
      except 0.4%. KEY POINTS: * A questionnaire can adequately identify patients under
      70 with renal dysfunction * 8% of patients referred to CT/MRI have an eGFR <45
      ml/min/1.73 m (2) * 55% reported risk factors, but renal dysfunction was only
      found in 13% * Patients over 70 years should have eGFR determined before CT *
      eGFR determination is not beneficial when stable MRI agents are used.

PMID- 24275805
TI  - Clinical investigation of flat panel CT following middle ear reconstruction: a
      study of 107 patients.
AB  - OBJECTIVES: After middle ear reconstruction using partial or total ossicular
      replacement prostheses (PORP/TORP), an air-bone gap (ABG) may persist because of
      prosthesis displacement or malposition. So far, CT of the temporal bone has
      played the main role in the diagnosis of reasons for postoperative insufficient
      ABG improvement. Recent experimental and clinical studies have evaluated flat
      panel CT (fpCT) as an alternative imaging technique that provides images with
      high isovolumetric resolution, fewer metal-induced artefacts and lower
      irradiation doses. METHODS: One hundred and seven consecutive patients with
      chronic otitis media with or without cholesteatoma underwent reconstruction by
      PORP (n = 52) or TORP (n = 55). All subjects underwent preoperative and
      postoperative audiometric testing and postoperative fpCT. RESULTS: Statistical
      evaluation of all 107 patients as well as the sole sub-assembly groups (PORP or
      TORP) showed a highly significant correlation between hearing improvement and
      fpCT-determined prosthesis position. FpCT enables detailed postoperative
      information on patients with middle ear reconstruction. CONCLUSIONS: FpCT is a
      new imaging technique that provides immediate feedback on surgical results after
      reconstructive middle ear surgery. Specific parameters evaluated by fpCT may
      serve as a predictive tool for estimated postoperative hearing improvement.
      Therefore this imaging technique is suitable for postoperative quality control in
      reconstructive middle ear surgery. KEY POINTS: * Flat panel CT offers advantages
      with regard to artefacts and radiation dose. * FpCT provides higher isovolumetric
      resolution of temporal bone and middle ear implants. * FpCT allows prediction of
      the postoperative hearing outcome in patients. * FpCT is an important tool for
      immediate postoperative quality control. * FpCT improves postoperative management
      of patients with complications following ossicular replacement.

PMID- 24275806
TI  - Quantitative analysis of emphysema and airway measurements according to iterative
      reconstruction algorithms: comparison of filtered back projection, adaptive
      statistical iterative reconstruction and model-based iterative reconstruction.
AB  - OBJECTIVES: To evaluate filtered back projection (FBP) and two iterative
      reconstruction (IR) algorithms and their effects on the quantitative analysis of
      lung parenchyma and airway measurements on computed tomography (CT) images.
      METHODS: Low-dose chest CT obtained in 281 adult patients were reconstructed
      using three algorithms: FBP, adaptive statistical IR (ASIR) and model-based IR
      (MBIR). Measurements of each dataset were compared: total lung volume, emphysema
      index (EI), airway measurements of the lumen and wall area as well as average
      wall thickness. Accuracy of airway measurements of each algorithm was also
      evaluated using an airway phantom. RESULTS: EI using a threshold of -950 HU was
      significantly different among the three algorithms in decreasing order of FBP
      (2.30 %), ASIR (1.49 %) and MBIR (1.20 %) (P < 0.01). Wall thickness was also
      significantly different among the three algorithms with FBP (2.09 mm)
      demonstrating thicker walls than ASIR (2.00 mm) and MBIR (1.88 mm) (P < 0.01).
      Airway phantom analysis revealed that MBIR showed the most accurate value for
      airway measurements. CONCLUSION: The three algorithms presented different EIs and
      wall thicknesses, decreasing in the order of FBP, ASIR and MBIR. Thus, care
      should be taken in selecting the appropriate IR algorithm on quantitative
      analysis of the lung. KEY POINTS: * Computed tomography is increasingly used to
      provide objective measurements of intra-thoracic structures. * Iterative
      reconstruction algorithms can affect quantitative measurements of lung and
      airways. * Care should be taken in selecting reconstruction algorithms in
      longitudinal analysis. * Model-based iterative reconstruction seems to provide
      the most accurate airway measurements.

PMID- 24275808
TI  - A tracheid-differentiation factor from pine needles.
AB  - Exogenous indol-3yl-acetic acid (IAA), alone and together with several
      cytokinins, was ineffective in promoting the complete differentiation into
      tracheids of cambial derivatives of Pinus contorta Dougl.; IAA alone promoted
      cambial cell division and primary-wall growth in cambial derivatives throughout
      the stem's length. In contrast, a single pair of needles on a stem cutting in
      light promoted neither cambial cell division nor primary-wall growth in cambial
      derivatives but did promote complete differentiation of cambial cells into
      tracheids; tracheids differentiated only near the junction of the foliated short
      shoot with the stem. Clear inter-and intracellular differences in the extent of
      tracheid differentiation occurred in response to a single needle pair and have
      suggested the hypothesis that a specific tracheid-differentiation factor
      regulates the differentiation of cells into proto-, meta-, or secondary-xylem
      tracheary elements through an interaction with IAA. 

PMID- 24275807
TI  - Double contrast-enhanced ultrasonography in preoperative Borrmann classification
      of advanced gastric carcinoma: comparison with histopathology.
AB  - The purpose of this study was to investigate the accuracy of double contrast
      enhanced ultrasonography (DCEUS) for assessing the Borrmann classification of
      advanced gastric carcinoma (AGC) preoperatively. Three hundred twenty nine
      patients with proved AGC were enrolled. DCEUS (intravenous microbubbles combined
      with combined with oral contrast-enhanced ultrasound) was performed
      preoperatively. The diagnostic accuracy of DCEUS in determining Borrmann
      classification was compared with postoperative pathological findings. The
      reliability of DCEUS was analyzed. The accuracy of DCEUS in determining the
      Borrmann classification of AGC was 91.49%. The intra- and inter-observer
      reproducibility was both almost perfect for assessing the Borrmann classification
      of AGC by DCEUS. DCEUS could be considered as an accurate, non-invasive, and
      reliable diagnostic method for preoperative Borrmann classification of advanced
      gastric carcinoma. 

PMID- 24275809
TI  - Maturation and germination of Phaseolus vulgaris embryonic axes in culture.
AB  - In this study of embryo development in Phaseolus vulgaris L., we found that
      immature embryonic axes placed in culture show a growth lag before germinating.
      The length of this lag phase varies according to axis age at excision, but is not
      affected by transfer to fresh medium, alteration of sucrose concentration between
      0.5 and 2%, or whether the culture medium is liquid or agar-solidified. The lag
      phase was shortened by both actinomycin D and cordycepin treatment, and by
      treatment with 10(-5) to 10(-6) M benzyladenine. The effect of abscisic acid
      (ABA) varied with concentration: below a certain level, it had no effect on the
      lag phase, but above that level it inhibited, germination. This threshold
      concentration was 10(-7) M for 20-d-old axes but increased to 10(-5) M by the
      time the axes were 32 to 34 d old. To determine whether the axes were continuing
      their embryonic development during the lag phase, we tested them for desiccation
      tolerance and for synthesis of phaseolin, a seed storage protein which is
      specific for embryos of P. vulgaris. The ability to germinate after rapid
      desiccation was acquired by axes at 26 d past anthesis; when axes younger than
      this were placed in culture, they developed desiccation-tolerance during the lag
      phase of growth, indicating that they were continuing embryonic maturation.
      Phaseolin was present in isolated axes, although at lower levels than in
      cotyledons. It accumulated during axis development in parallel with total
      protein, staying at about 1% of total protein content. When isolated immature
      axes were pulsed with (3)H-or (14)C-amino acids, they incorporated label into
      phaseolin, shown by precipitation with anti-phaseolin antibody. Isolated axes
      from mature seeds, however, did not synthesize detectable amounts of phaseolin.
      Immature axes cultured in vitro for a period of one to several days continued
      synthesizing phaseolin until the day prior to visible germination. Treatment of
      cultured axes with ABA increased the amount of precursor amino acids incorporated
      into protein, but had a small or no effect on the relative proportion of
      phaseolin synthesized. We conclude that P. vulgaris axes in culture continue to
      develop embryonically for a period of time which seems to be under intrinisc
      control by the axis. This contrasts with "precocious germanation", a pattern of
      embryo behavior seen in many other species. When such embryos are excised from
      seeds while immature and placed in culture, they switch promptly from embryo
      development into germination. If ABA or water stress is responsible for
      preventing precocious germination, it may be that a high level of ABA is
      maintained or synthesized internally by embryonic axes of Phaseolus, while in
      other embryos the maternal environment supplies ABA and/or causes water stress. 

PMID- 24275810
TI  - Photosynthesis under osmotic stress : Inhibition of photosynthesis of intact
      chloroplasts, protoplasts, and leaf slices at high osmotic potentials.
AB  - 1. Photosynthesis of leaf slices, mesophyll protoplasts, and intact chloroplasts
      of spinach was inhibited in hypertonic sorbitol solutions. Sorbitol could be
      replaced by other nonpenetrating osmotica such as sucrose or glycinebetaine. As a
      penetrating solute, ethyleneglycol was also inhibitory, but osmolarities required
      for inhibition of photosynthesis were considerably higher than in the case of non
      penetrating osmotica.-2. With leaf slices and protoplasts, 50% inhibition by
      sorbitol was usually observed at osmotic potentials between 25 and 40 bar. With
      isolated intact chloroplasts, the osmotic potentials producing 50% inhibition
      varied considerably. Depending on the growth conditions of the plant material,
      50% inhibition occurred between 14 and 40 bar. The integrity of the chloroplast
      envelope as measured by the accessibility of the thylakoid system for
      ferricyanide was not affected by osmotic stress.-3. Quantum requirements for CO2
      assimilation and reduction of 3-phosphoglycerate or nitrite by intact
      chloroplasts increased under osmotic stress. The increase was larger for CO2
      reduction than for reduction of 3-phosphoglycerate or nitrite.-4. In intact
      chloroplasts, electron transport to methylviologen was not much affected by
      osmotic stress. Basal electron transport was not stimulated, suggesting absence
      of uncoupling.-5. The increase in ATP/ADP ratios on illumination of intact
      chloroplasts was slower at an osmotic potential of 36 bar than at 11 bar.-6. The
      results indicate that inhibition of photosynthesis is not caused by the
      sensitivity of a single photosynthetic reaction to increased osmotic potentials.
      Rather, several reactions are sensitive to water stress. Osmotic stress acts on
      the photosynthetic apparatus mainly at the level of dark reactions and ATP
      synthesis, and much less on primary photoreactions or electron transport, between
      water and the primary oxidant of photosystem I.-7. The different sensitivity of
      chloroplasts to penetrating and non-penetrating solutes and the observed
      variability of chloroplast sensitivity to stress suggests that the reduction in
      water potential is not directly responsible for damage to the photosynthetic
      apparatus during osmotic stress. Rather, the composition of the chloroplasts
      appears to be a decisive factor which determines sensitivity or resistance to
      osmotic stress. 

PMID- 24275811
TI  - Photosynthesis under osmotic stress : Effect of high solute concentrations on the
      permeability properties of the chloroplast envelope and on activity of stroma
      enzymes.
AB  - 1. Increasing the sorbitol concentration in a suspension of intact chloroplasts
      induced a fast, transient and not very specific efflux of metabolites from
      chloroplasts to the medium. Stroma proteins were retained by the chloroplasts. 2.
      Within the first 30 s following hypertonic stress, the chloroplast volume
      decreased according to the Boyle-Mariotte relation. A subsequent and transient
      increase suggested some influx of external solute. 3. Dark reactions of intact
      chloroplasts such as starch degradation and formation of labelled 3
      phosphoglycerate from dihydroxyacetone phosphate or ribose-5-phosphate and
      (14)CO2 were inhibited at low water potentials. After chloroplast rupture, the
      activity of stromal enzymes was decreased by high solute concentrations. Ribulose
      bisphosphate carboxylase exhibited a decrease of Vmax, while KmCO 2 remained
      unaltered. With sorbitol, sucrose, glycerol or glycinebetaine, 50% inhibition of
      enzymes was observed at osmotic potentials between 40 and 50 bar, with
      ethyleneglycol at about 70 bar. With salts such as KCl, 50% inhibition was found
      at 15 to 20 bar. 4. A comparison between inhibition of photosynthesis in intact
      chloroplasts and inhibition of enzymes in stroma extracts by solutes supports the
      notion that inhibition of photosynthesis at high osmotic potentials is mainly a
      solute effect. Another factor contributing to inhibition of photosynthesis in
      isolated chloroplasts is the loss of intermediates and cofactors which occurs
      during rapid osmotic dehydration. 

PMID- 24275812
TI  - Photosynthesis under osmotic stress : Differential recovery of photosynthetic
      activities of stroma enzymes, intact chloroplasts, protoplasts, and leaf slices
      after exposure to high solute concentrations.
AB  - The reversibility of the inhibition of photosynthetic reactions by water stress
      was examined with four systems of increasing complexity-stromal enzymes, intact
      chloroplasts, mesophyll protoplasts, and leaf slices. The inhibition of soluble
      chloroplast enzymes by high solute concentrations was instantly relieved when
      solutes were properly diluted. In contrast, photosynthesis was not restored but
      actually more inhibited when isolated chloroplasts exposed to hypertonic stress
      were transferred to conditions optimal for photosynthesis of unstressed
      chloroplasts. Upon transfer, chloroplast volumes increased beyond the volumes of
      unstressed chloroplasts, and partial envelope rupture occurred. In protoplasts
      and leaf slices, considerable and rapid, but incomplete restoration of
      photosynthesis was observed during transfer from hypertonic to isotonic
      conditions. Chloroplast envelopes did not rupture in situ during water uptake. It
      is concluded that inhibition of photosynthesis by severe water stress is at the
      biochemical level brought about in part by reversible inhibition of chloroplast
      enzymes and in part by membrane damage which requires repair mechanisms for
      reversibility. Both soluble enzymes and membranes appear to be affected by the
      increased concentration of internal solutes, which is caused by dehydration. 

PMID- 24275813
TI  - Isolation and characterization of aminopterin-resistant cell lines in maize.
AB  - Aminopterin-resistant cell lines of maize were isolated by two different
      procedures of callus selection and by plating suspension cultures on
      drugcontaining medium after mutagen treatment. Efficiencies of different methods
      of variant selection were compared. Four aminopterin-resistant cell lines were
      shown to be 10-40 times more resistant than the parental cell line, and they were
      also resistant to another folate analog, methotrexate. The results suggest that
      alterations in at least three different cell properties could be responsible for
      resistance; 1) increased dihydrofolate reductase activity, 2) altered aminopterin
      sensitivity of dihydrofolate reductase, and 3) reduced drug uptake. One of the
      resistant cell lines showed more than one alteration, but its resistance proved
      to be unstable. The results suggest that stable changes which may or may not be
      of genetic origin and also unstable physiological changes or a combination of
      both could lead to aminopterin resistance in maize cell cultures. 

PMID- 24275814
TI  - Effect of zearalenone (F-2) on pea stem, maize root, and rat liver mitochondria.
AB  - At 5 and 10 MUg ml(-1) concentration, zearalenone (F-2), a mycotoxin produced by
      a number of species of the genus Fusarium, causes an inhibition of the oxidative
      phosphorylation of isolated plant mitochondria, while at 20 and 40 MUg ml(-1) it
      causes uncoupling. However, when the mitochondria are pre-incubated for 20 min
      with F-2, the uncoupling appears to be the prevailing effect. F-2 is also able to
      inhibit the mitochondrial ATPase activity (Mg(2+)-dependent). Conversely, F-2 (40
      MUg ml(-1)) does not alter the ATP level of maize roots and only slightly affects
      the ATPase activity of pea stem and maize root microsomal fractions. In addition,
      F-2 (10-40 MUg ml(-1)) inhibits ATP synthesis catalyzed by rat liver
      mitochondria. It is suggested that the phytotoxicity of F-2, also known for its
      ability to collapse the transmembrane electric potential of maize roots, may be
      mainly linked to its ability to increase the proton permeability of the cell,
      similar to the common uncouplers. 

PMID- 24275815
TI  - Auxin binding in roots: A comparison between maize roots and coleoptiles.
AB  - Auxin binding onto membrane fractions of primary roots of maize seedlings has
      been demonstrated using naphth-1yl-acetic acid (NAA) and indol-3yl-acetic acid
      (IAA) as ligands. This binding is compared with the already well characterized
      interaction between auxins and coleoptile membranes. The results indicate that
      while kinetic parameters are of the same order for root and coleoptile binding, a
      number of differences occur with respect to location in cells and relative
      affinity. The possible significance of the existence of such binding sites in
      root cells is discussed in relation to auxin action. 

PMID- 24275816
TI  - Abscisic acid distribution in horizontal maize root segments.
AB  - Using gas chromatography-mass spectrometry (GC/MS) techniques of analyses, it has
      been found that endogenous abscisic acid (ABA) becomes asymmetrically distributed
      in the elongation zone of horizontal Zea mays (cv. LG 11) roots which are showing
      a positive gravitropic response. There is a relative increase in the ABA content
      of the lower half and a concomitant decrease for the upper half in such roots.
      Asymmetric distribution of ABA is also detected in the elongation zone of half
      decapped roots. 

PMID- 24275817
TI  - Glucosylation of flavonoids in petals of Petunia hybrida.
AB  - During the biosynthesis of anthocyanins in Petunia hybrida, the 3-hydroxyl group
      is glucosylated. Their supposed biosynthetic precursors, the dihydroflavonols,
      are glucosylated at the 7 or 4' positions. The question arose of whether these
      glucosides or the aglucones act as a substrate in anthocyanin synthesis. Using
      isolated flower buds of white flowering mutants that were blocked in an earlier
      step of biosynthesis, it was found that anthocyanin-3-glucosides and
      dihydroquercetin-7-glucoside were synthesized if dihydroquercetin,
      dihydroquercetin-7-glucoside, or dihydroquercetin-4'-glucoside were used as
      precursors in these experiments. Intracellular dihydroquercetin-glucosides were
      not used as a substrate for anthocyanin synthesis. The results are explained by
      deglucosylation of dihydroquercetin-glucosides during uptake by isolated flower
      limbs. Dihydroquercetin-7-glucoside, formed intracellularly, is not available as
      a precursor for anthocyanins. We conclude that the aglucone form of
      dihydroquercetin acts as a substrate in anthocyanin biosynthesis. 

PMID- 24275818
TI  - Modification of the B-ring during flavonoid synthesis in Petunia hybrida: Effect
      of the hydroxylation gene Hf1 on dihydroflavonol intermediates.
AB  - The white flowering mutant W48 of Petunia hybrida is dominant for the
      hydroxylation gene Hf1 and homozygous recessive for the hydroxylation gene Ht1
      and the anthocyanin gene An1. Flower buds of this mutant accumulate
      dihydrokaempferol-glucosides. Thus the effect of Hf1 being dominant is not the
      hydroxylation of the C15 skeleton, as is the case in mutants that are able to
      synthesize anthocyanins. This can be explained either by a feed-back inhibition
      of the hydroxylation by small amounts of dihydromyricetin (glucosides), or by a
      controlling effect of the gene An1 on the expression of Hf1. However, the white
      flowering mutant W58, which is homozygous recessive for the gene An6 and dominant
      for Hf1, accumulates dihydromyricetin (glucosides). This excludes a possible feed
      back inhibition by dihydromyricetin and we conclude that An1 controls the
      expression of Hf1. Feeding of radioactive malonic acid to isolated flower limbs
      of mutants able to synthesize anthocyanins, leads to the incorporation of
      radioactivity into dihydrokaempferol (glucosides) and dihydroquercetin
      (glucosides). These results show that glucosylation of dihydroflavonols is a
      normal event in anthocyanin biosynthesis and is not induced by an inhibition of
      anthocyanin synthesis. 

PMID- 24275819
TI  - Comparison of somatic and sexual incompatibility between Datura innoxia and
      Atropa belladonna.
AB  - After protoplast fusion somatic hybrid calli were obtained by complementation
      selection between an albino mutant of Datura innoxia and the wildtype of Atropa
      belladonna (Krumbiegel and Schieder, 1979. Planta 145, 371-375). In the present
      study experiments are described concerning leaf and shoot induction on several
      media supplemented with different combinations and concentrations of hormones.
      Except for fleshy leaves and embryos, no well-formed shoot could be obtained.
      However, under standard culture conditions after one and a half years, one line
      produced numerous green shoots, showing a reduced number of chromosomes from
      Atropa belladonna. The loss of some chromosomes decreased the degree of somatic
      incompatibility. The additional appearance of shoots with albino sectors, of
      total albino shoots, and of green shoots showing a different phenotype,
      demonstrated that the elimination of the chromosomes occurred not only once, but
      several times. At least one shoot nearly stable in chromosome content and green
      subline could be obtained possessing only 6 chromosomes of Atropa belladonna and
      the original chromosome number of Datura innoxia. Experiments were carried out to
      test the feasibility of producing sexual hybrids through in vivo and in vitro
      methods by cross pollination. However, no embryos, seeds, or plantlets were
      obtained, thus demonstrating that protoplast fusion is the only possibility for
      obtaining hybrids between these two species. 

PMID- 24275820
TI  - Light-induced inhibitors from intact and cultured caps of Zea roots.
AB  - Growth inhibitors were assayed from extracts of intact (attached) and of excised
      (cultured) root caps of Zea mays L., cv. Merit, the roots of which show a
      positive geotropic response only after exposure to light. If caps are intact at
      the time of illumination, at least two inhibitory substances are produced, an
      acid inhibitor and a neutral inhibitor, whereas if caps are detached from roots,
      placed in culture and then illuminated only the neutral inhibitor is formed.
      Cycloheximide retards inhibitor production in both intact and cultured caps. When
      [(14)C]mevalonic acid is included in the culture medium and the caps are
      illuminated, 15-25% of the recoverable (14)C cochromatographs with the neutral
      inhibitor, whereas in caps cultured in the dark, this radiolabelling pattern is
      not observed. Cyloheximide in the light reduces the incorporation of (14)C into
      compounds cochromatographing at the Rf of the neutral inhibitor. It is suggested
      that the neutral inhibitor may be important in the light-induced bending of
      roots. 

PMID- 24275821
TI  - Effect of choline chloride on fatty acid chain ordering in membranes of wheat
      (Triticum aestvium L. cv. Miranovskaja 808).
AB  - A winter variety (Miranovskaja 808) of wheat (Triticum aestivum L.) was grown in
      water cultures containing 0, 5, 15, 30, and 60 mM choline chloride. There was an
      increase in the phosphatidylcholine level at the expense of phosphatidic acid,
      parallel with an increasing choline concentration in the cultivating medium.
      While the ratio of free sterols to phospholipids remained essentially constant in
      the seedlings, there was an increase in the ratio of saturated-to-unsaturated
      fatty acids of the phospholipid fraction. Probing the protoplasts obtained from
      the leaves of the seedlings, with spin labeled 5-doxyl- and 16-doxyl stearic
      acids, indicated a progressive rigidifying of the hydrophobic core of the
      plasmalemma. It is suggested that this is a manifestation of compensatory
      mechanisms by which plants attempt to maintain unchanged average membrane
      fluidity across their membranes in response to the fluidizing effect of choline
      head groups. 

PMID- 24275822
TI  - Evidence of de novo synthesis of maltose excreted by the endosymbiotic Chlorella
      from Paramecium bursaria.
AB  - The endosymbiotic Chlorella sp. from Paramecium bursaria excretes maltose both in
      the light and in the dark. Experiments on photosynthetic (14)CO2 fixation and
      (14)CO2 pulse-chase experiments show that maltose is synthesized in the light
      directly from compounds of the Calvin cycle, whereas in the dark it results from
      starch degradation. 

PMID- 24275823
TI  - The electrochemical proton gradient and its influence on citrate uptake in
      tonoplast vesicles of Hevea brasiliensis.
AB  - The relationship between the electrochemical proton gradient, Delta MUH+ (-) ,
      and citrate transport has been studied in tonoplast vesicles from Hevea
      brasiliensis (the rubber tree). Vesicles were generated from lyophilized samples
      of fresh vacuoles obtained from the latex sap. Methylamine was used to measure
      intravesicular pH and lipophilic ions to determine the electrical potential
      difference (DeltaPsi) across the tonoplast. When incubated at pH 7.5 in the
      absence of ATP, the tonoplast vesicles showed a DeltapH of 0.6 units (interior
      acid) and a DeltaPsi of about-100 mV (interior negative). This potential is
      thought to be made up of contributions from an H(+) diffusion potential,
      diffusion potentials from other cations and a Donnan potential arising from the
      presence of internal citrate. In the presence of 5 mol m(-3) MgATP the DeltapH
      was increased to about 1.0 unit and the DeltaPsi to about-10 mV. Under these
      conditions the proton-motive force (Delta p Delta MUH+ (-) /F) became positive
      and reached +50 mV. These effects were specific to MgATP (ADP and Mg(2+) having
      no significant effect) and were prevented by the protonophore p
      trifluoromethoxycarbonylcyanidephenylhydrazone (FCCP). Citrate uptake by the
      vesicles was markedly stimulated by MgATP; ADP and Mg(2+) again had no effect.
      Nigericin greatly increased DeltapH and this was associated with a large increase
      in citrate accumulation. The results indicate that the vesicle membrane possesses
      a functional H(+)-translocating ATPase. The Delta MUH+ (-) generated by this
      ATPase can be used to drive citrate uptake into the vesicles. The properties of
      the tonoplast vesicles are compared with those of the fresh latex vacuoles. 

PMID- 24275824
TI  - Effect of gibberellic acid on ion uptake selectivity in pea seedlings.
AB  - Gibberellic acid reduced the uptake of nitrogen and phosphorus relative to the
      cations, a common reponse in the three pea cultivars studied. In addition, in the
      cv. Progress, it increased the uptake of calcium relative to magnesium and
      potassium. No effect in the proportion in which cations are absorbed was
      noticeable in the other two varieties. Ion uptake is modified by gibberellic acid
      through its influence on the sink strength of the shoot, the size and geometry of
      the root system, and the selectivity in uptake. The overall effect may result in
      a stimulation or an inhibition, depending on the ion considered and the pea
      cultivar. 

PMID- 24275825
TI  - Acidic organic compounds in beverage, food, and feed production.
AB  - Organic acids and their derivatives are frequently used in beverage, food, and
      feed production. Acidic additives may act as buffers to regulate acidity,
      antioxidants, preservatives, flavor enhancers, and sequestrants. Beneficial
      effects on animal health and growth performance have been observed when using
      acidic substances as feed additives. Organic acids could be classified in groups
      according to their chemical structure. Each group of organic acids has its own
      specific properties and is used for different applications. Organic acids with
      low molecular weight (e.g. acetic acid, lactic acid, and citric acid), which are
      part of the primary metabolism, are often produced by fermentation. Others are
      produced more economically by chemical synthesis based on petrochemical raw
      materials on an industrial scale (e.g. formic acid, propionic and benzoic acid).
      Biotechnology-based production is of interest due to legislation, consumer demand
      for natural ingredients, and increasing environmental awareness. In the United
      States, for example, biocatalytically produced esters for food applications can
      be labeled as "natural," whereas identical conventional acid catalyst-based
      molecules cannot. Natural esters command a price several times that of non
      natural esters. Biotechnological routes need to be optimized regarding raw
      materials and yield, microorganisms, and recovery methods. New bioprocesses are
      being developed for organic acids, which are at this time commercially produced
      by chemical synthesis. Moreover, new organic acids that could be produced with
      biotechnological methods are under investigation for food applications.

PMID- 24275826
TI  - Anatomical parameters of fifth lumbar vertebra in L5-S1 spondylolytic
      spondylolisthesis from a surgical point of view.
AB  - PURPOSE: We measured the length, width, height, and angles related to both
      Meyerding grading system and Marchetti-Bartolozzi classification in L5-S1
      spondylolytic spondylolisthesis patients to investigate the anatomical
      characteristics of fifth lumbar pedicles. METHODS: Seventy patients with L5-S1
      spondylolytic spondylolisthesis and general spinal disease were included. Patient
      attributes, Meyerding grading system and Marchetti-Bartolozzi classification of
      spondylolisthesis, length, width, height of L4 and L5 pedicle, and the angle
      between pedicle and vertebral midline were measured. The heights of L5 vertebral
      body, divided as anterior, mid, and posterior were also measured. RESULTS: The
      pedicle is elongated and the angle of the pedicle is wider in cases of L5-S1
      spondylolysis. Vertebral body shape was more posteriorly wedged in L5-S1
      spondylolysis. Pedicles were more narrow and shorter in L5-S1 spondylolysis.
      CONCLUSIONS: In L5-S1 spondylolytic spondylolisthesis, a longer screw is suitable
      for insertion of L5 pedicle and the screw should be inserted more medially
      compared to patients without spondylolysis.

PMID- 24275827
TI  - Cathodal tDCS over the left prefrontal cortex diminishes choice-induced
      preference change.
AB  - In everyday life, people often find themselves facing difficult decisions between
      options that are equally attractive. Cognitive dissonance theory states that
      after making a difficult choice between 2 equally preferred options, individuals
      no longer find the alternatives similarly desirable. Rather, they often change
      their existing preferences to align more closely with the choice they have just
      made. Despite the relevance of cognitive dissonance in modulating behavior,
      little is known about the brain processes crucially involved in choice-induced
      preference change. In the present study, we applied cathodal transcranial Direct
      Current Stimulation (tDCS) with the aim of downregulating the activity of the
      left or the right dorsolateral prefrontal cortex (DLPFC) during a revised version
      of Brehm's (in 1956. Post-decision changes in the desirability of alternatives. J
      Abnorm Soc Psychol. 52:384-389) free-choice paradigm. We found that cathodal tDCS
      over the left, but not over the right, DLPFC caused a reduction of the typical
      behavior-induced preference change relative to sham stimulation. Our findings
      highlight the role of prefrontal cortex in cognitive dissonance and provide
      evidence that left DLPFC plays a necessary role in the implementation of choice
      induced preference change. 

PMID- 24275828
TI  - Temporal organization of GABAergic interneurons in the intermediate CA1
      hippocampus during network oscillations.
AB  - Travelling theta oscillations and sharp wave-associated ripples (SWRs) provide
      temporal structures to neural activity in the CA1 hippocampus. The contribution
      of rhythm-generating GABAergic interneurons to network timing across the
      septotemporal CA1 axis remains unknown. We recorded the spike-timing of
      identified parvalbumin (PV)-expressing basket, axo-axonic, oriens-lacunosum
      moleculare (O-LM) interneurons, and pyramidal cells in the intermediate CA1
      (iCA1) of anesthetized rats in relation to simultaneously detected network
      oscillations in iCA1 and dorsal CA1 (dCA1). Distinct interneuron types were
      coupled differentially to SWR, and the majority of iCA1 SWR events occurred
      simultaneously with dCA1 SWR events. In contrast, iCA1 theta oscillations were
      shifted in time relative to dCA1 theta oscillations. During theta cycles, the
      highest firing of iCA1 axo-axonic cells was followed by PV-expressing basket
      cells and subsequently by O-LM together with pyramidal cells, similar to the
      firing sequence of dCA1 cell types reported previously. However, we observed that
      this temporal organization of cell types is shifted in time between dCA1 and
      iCA1, together with the respective shift in theta oscillations. We show that
      GABAergic activity can be synchronized during SWR but is shifted in time from
      dCA1 to iCA1 during theta oscillations, highlighting the flexible inhibitory
      control of excitatory activity across a brain structure. 

PMID- 24275829
TI  - Functional and effective hippocampal-neocortical connectivity during construction
      and elaboration of autobiographical memory retrieval.
AB  - Autobiographical memory (AM) provides the opportunity to study interactions among
      brain areas that support the search for a specific episodic memory
      (construction), and the later experience of mentally reliving it (elaboration).
      While the hippocampus supports both construction and elaboration, it is unclear
      how hippocampal-neocortical connectivity differs between these stages, and how
      this connectivity involves the anterior and posterior segments of the
      hippocampus, as these have been considered to support the retrieval of general
      concepts and recollection processes, respectively. We acquired fMRI data in 18
      healthy participants during an AM retrieval task in which participants were asked
      to access a specific AM (construction) and then to recollect it by recovering as
      many episodic details as possible (elaboration). Using multivariate analytic
      techniques, we examined changes in functional and effective connectivity of
      hippocampal-neocortical interactions during these phases of AM retrieval. We
      found that the left anterior hippocampus interacted with frontal areas during
      construction and bilateral posterior hippocampi with visual perceptual areas
      during elaboration, indicating key roles for both hippocampi in coordinating
      transient neocortical networks at both AM stages. Our findings demonstrate the
      importance of direct interrogation of hippocampal-neocortical interactions to
      better illuminate the neural dynamics underlying complex cognitive tasks such as
      AM retrieval. 

PMID- 24275831
TI  - Intraparietal sulcus activity and functional connectivity supporting spatial
      working memory manipulation.
AB  - The intraparietal sulcus (IPS) is recruited during tasks requiring attention,
      maintenance and manipulation of information in working memory (WM). While WM
      tasks often show broad bilateral engagement along the IPS, topographic maps of
      contralateral (CL) visual space have been identified along the IPS, similar to
      retinotopic maps in visual cortex. In the present study, we asked how these
      visuotopic IPS regions are differentially involved in the maintenance and
      manipulation of spatial information in WM. Visuotopic mapping was performed in 26
      participants to define regions of interest along the IPS, corresponding to
      previously described IPS0-4. In a separate task, we showed that while maintaining
      the location of a briefly flashed target in WM preferentially engaged CL IPS,
      manipulation of spatial information by mentally rotating the target around a
      circle engaged bilateral IPS, peaking in IPS1 in most participants. Functional
      connectivity analyses showed increased interaction between the IPS and prefrontal
      regions during manipulation, as well as interhemispheric interactions. Two
      control tasks demonstrated that covert attention shifts, and nonspatial
      manipulation (arithmetic), engaged patterns of IPS activation and connectivity
      that were distinct from WM manipulation. These findings add to our understanding
      of the role of IPS in spatial WM maintenance and manipulation. 

PMID- 24275830
TI  - Separable roles for attentional control sub-systems in reading tasks: a combined
      behavioral and fMRI study.
AB  - Attentional control is important both for learning to read and for performing
      difficult reading tasks. A previous study invoked 2 mechanisms to explain
      reaction time (RT) differences between reading tasks with variable attentional
      demands. The present study combined behavioral and neuroimaging measures to test
      the hypotheses that there are 2 mechanisms of interaction between attentional
      control and reading; that these mechanisms are dissociable both behaviorally and
      neuro-anatomically; and that the 2 mechanisms involve functionally separable
      control systems. First, RT evidence was found in support of the 2-mechanism
      model, corroborating the previous study. Next, 2 sets of brain regions were
      identified as showing functional magnetic resonance imaging blood oxygen level
      dependent activity that maps onto the 2-mechanism distinction. One set included
      bilateral Cingulo-opercular regions and mostly right-lateralized Dorsal Attention
      regions (CO/DA+). This CO/DA+ region set showed response properties consistent
      with a role in reporting which processing pathway (phonological or lexical) was
      biased for a particular trial. A second set was composed primarily of left
      lateralized Frontal-parietal (FP) regions. Its signal properties were consistent
      with a role in response checking. These results demonstrate how the subcomponents
      of attentional control interact with subcomponents of reading processes in
      healthy young adults. 

PMID- 24275832
TI  - Relational associative learning induces cross-modal plasticity in early visual
      cortex.
AB  - Neurobiological theories of memory posit that the neocortex is a storage site of
      declarative memories, a hallmark of which is the association of two arbitrary
      neutral stimuli. Early sensory cortices, once assumed uninvolved in memory
      storage, recently have been implicated in associations between neutral stimuli
      and reward or punishment. We asked whether links between neutral stimuli also
      could be formed in early visual or auditory cortices. Rats were presented with a
      tone paired with a light using a sensory preconditioning paradigm that enabled
      later evaluation of successful association. Subjects that acquired this
      association developed enhanced sound evoked potentials in their primary and
      secondary visual cortices. Laminar recordings localized this potential to
      cortical Layers 5 and 6. A similar pattern of activation was elicited by
      microstimulation of primary auditory cortex in the same subjects, consistent with
      a cortico-cortical substrate of association. Thus, early sensory cortex has the
      capability to form neutral stimulus associations. This plasticity may constitute
      a declarative memory trace between sensory cortices. 

PMID- 24275834
TI  - Hypertension: the Symplicity of renal denervation.

PMID- 24275833
TI  - GAD67 deficiency in parvalbumin interneurons produces deficits in inhibitory
      transmission and network disinhibition in mouse prefrontal cortex.
AB  - In mammalian neocortex, the delicate balance of neural circuits is regulated by a
      rich repertoire of inhibitory control mechanisms mediated by diverse classes of
      GABAergic interneurons. A key step common to all GABAergic neurons is the
      synthesis of GABA, catalyzed by 2 isoforms of glutamic acid decarboxylases (GAD).
      Among these, GAD67 is the rate-limiting enzyme. GAD67 level is regulated by
      neural activity and is altered in multiple neuropsychiatric disorders. The
      significance of altered GAD67 levels on inhibitory transmission, however, remains
      unclear. The presence of GAD65, postsynaptic GABA receptor regulation, and the
      diversity of cortical interneurons make the link from GAD67 levels to GABA
      transmission less than straightforward. Here, we selectively removed one allele
      of the GAD67 gene, Gad1, in PV interneurons in juvenile mice. We found
      substantial deficits in transmission from PV to pyramidal neurons in prefrontal
      cortex, along with increases of pyramidal cell excitability and
      excitation/inhibition balance in PV cells. Synaptic deficits recovered in adult
      mice, suggesting engagement of homeostatic and compensatory mechanisms. These
      results demonstrate that GAD67 levels directly influence synaptic inhibition.
      Thus, GAD67 deficiency in PV cells likely contributes to cortical dysfunction in
      disease states; the reversibility of synaptic deficits suggests nonpermanent
      damage to inhibitory circuitry. 

PMID- 24275835
TI  - Chronic kidney disease: Psoriasis--a risk factor for chronic kidney disease?
AB  - A new study presents compelling evidence of an association between moderate to
      severe psoriasis and chronic kidney disease (CKD). This association seems to be
      independent of traditional CKD risk factors and indicates that monitoring of
      kidney function in patients with psoriasis is warranted.

PMID- 24275836
TI  - Glomerular disease: the role of parietal epithelial cells in hyperplastic
      lesions.
AB  - Parietal epithelial cells (PECs) are increasingly recognized as key players in
      the pathogenesis of proliferative glomerular diseases. A new study by Rizzo and
      colleagues contributes to this emerging concept and identifies potential novel
      signalling pathways that might mediate the activation of PECs. However, the
      functional role of PECs remains controversial.

PMID- 24275837
TI  - Clinical trials: High-impact session from kidney week.

PMID- 24275838
TI  - Destiffening effect of valsartan and atenolol: influence of heart rate and blood
      pressure.
AB  - OBJECTIVE: We investigated data in 373 patients from the EXPLOR trial to
      determine the influence of heart rate (HR) and blood pressure (BP) on aortic
      stiffness in response to beta-blockade or angiotensin 2 type 1 receptor
      antagonism, administered during 24 weeks. METHODS: Carotid-femoral pulse wave
      velocity (PWV) was measured with aplanation tonometry (Sphygmocor ) after 8 (W8)
      and 24 weeks (W24) of treatment by the single-pill combination valsartan
      amlodipine (80/5  mg, then 160/10  mg) or an atenolol-amlodipine combination
      (50/5  mg, then 100/10  mg) in a prospective, randomized, parallel-groups
      multicenter trial with PROBE design. Drugs were up-titrated at W8. We analyzed
      the changes in PWV in relation with the changes in BP and HR, and major
      covariates, using mixed models in each treatment arm. RESULTS: The unadjusted
      reductions in mean BP and PWV were not significantly different between groups. HR
      was significantly reduced in the atenolol group, but not in the valsartan group.
      After adjustment on BP and HR, PWV significantly decreased with valsartan [-0.37 
      m/s (-0.70 to -0.08) at W8 and -0.43 (-0.76 to -0.10) m/s at W24], whereas no
      significant change was observed after atenolol [-0.16  m/s (-0.49 to 0.17) at W8
      and -0.05 (-0.35 to 0.44) m/s at W24]. CONCLUSION: These findings suggest that
      the reduction in PWV observed after atenolol could be explained by changes in BP
      and HR, whereas in patients treated by valsartan, about half of the decrease in
      aortic stiffness was BP-independent.

PMID- 24275840
TI  - Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically
      hypertensive mice.
AB  - OBJECTIVE: BPH/2J hypertensive mice have an exaggerated sympathetic contribution
      to blood pressure (BP). Premotor sympathetic neurons within the
      rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor
      tone and major site of action of the centrally acting sympatholytic agent,
      rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus
      normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM
      in the sympathetic contribution to hypertension in BPH/2J mice. METHODS: BPH/2J
      and BPN/3J mice were pre-implanted with telemetry devices to measure BP in
      conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group),
      orally for 14 days, at a wide range of doses (n=5/group), and also infused
      intracerebroventricularly for 7 days (n=6/group). RESULTS: Acute intraperitoneal
      rilmenidine induced greater depressor and bradycardic responses in BPH/2J than
      BPN/3J mice (Pstrain<0.01). Both responses were reduced by atropine pre
      treatment, with the remaining hypotensive effect being small and comparable
      between strains (Pstrain=1.0). This suggests that vagally induced reductions in
      cardiac output were responsible for the hypotension. Chronic
      intracerebroventricularly infused rilmenidine reduced BP from baseline marginally
      in BPH/2J mice during the dark (active) period (-6.5 +/- 2 mmHg; P=0.006).
      Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal
      effect on 24-h BP in both strains (P>0.16). CONCLUSION: The sympathetic vasomotor
      inhibitory effect of rilmenidine is minimal in both strains and similar in
      hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not
      likely mediated by greater neuronal activity in the RVLM, and agents such as
      rilmenidine would be an ineffective treatment for this form of neurogenic
      hypertension.

PMID- 24275839
TI  - Excess dietary sodium and inadequate potassium intake by hypertensive patients in
      Italy: results of the MINISAL-SIIA study program.
AB  - INTRODUCTION: The aim of the study was to assess the age-specific, sex-specific,
      and region-specific average sodium and potassium intake and its association with
      anthropometric characteristics in a sample of the Italian adult hypertensive
      population. METHODS: A total of 1232 hypertensive patients were recruited
      consecutively by 47 centers recognized by the Italian Society of Hypertension.
      The enrolled participants were on stable antihypertensive treatment.
      Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium
      excretion were measured and used as proxy for the average daily sodium and
      potassium intake. RESULTS: The average sodium intake was 172  mmol (or 10.1  g of
      salt/day) among men and 138 (or 8.1) among women, with no difference among
      geographical areas. Over 90% of men and 81% of women had a consumption higher
      than the recommended standard dietary intake of 5  g/day. The average potassium
      intake was 63 and 56  mmol, respectively in men and women, again without
      geographical differences, nearly 92% of men and 95% of women having an intake
      lower than the recommended intake (100  mmol/day or 3.9  g/day). There was a
      significant trend to a gradual decrease in sodium intake with age in both sexes
      (P <0.001). There was also a direct association between BMI and sodium intake in
      both sexes, this association being independent of age (P < 0.001). CONCLUSION: In
      this national sample of the Italian hypertensive population, dietary sodium
      intake was largely higher and potassium intake much lower than the recommended
      intakes, and this was true for all geographical areas. Overweight and obese
      hypertensive patients had particularly high sodium intakes.

PMID- 24275841
TI  - In prehypertension leukocytosis is associated with body mass index but not with
      blood pressure or incident hypertension.
AB  - BACKGROUND: Previous studies reported increased white blood cell counts (WBCCs),
      an inflammatory marker, in hypertension, prehypertension and metabolic syndrome.
      Evidence suggests that inflammation precedes blood pressure (BP) elevation and
      may contribute to incident hypertension. Angiotensin receptor blockers (ARBs) may
      reduce inflammation. We analyzed WBCC trends in TRial Of Preventing HYpertension
      (TROPHY) to determine if this inflammatory marker predicted incident hypertension
      in prehypertensive individuals and whether randomized assignment to the ARB
      candesartan (391 individuals) for 2 years, lowered WBCC compared with placebo
      treated controls (381 individuals). METHODS: A new analysis of TROPHY trial data.
      RESULTS: In the total population, baseline BMI correlated with WBCC (r = 0.185, P
      < 0.0001), neutrophils (r = 0.135, P < 0.001) and lymphocytes (r = 0.204, P <
      0.0001). Baseline triglycerides also correlated significantly with inflammatory
      markers. Despite a wide range of home BP (HBP) values, HBP did not correlate with
      baseline WBCC counts. After 2 years, candesartan decreased placebo corrected HBP
      by -5.5/-2.5 mmHg, (P < 0.0001), but WBCC, neutrophil and lymphocyte counts were
      not different in placebo and in candesartan groups. Baseline WBCC, neutrophils
      and lymphocyte counts did not predict incident hypertension in the placebo group.
      CONCLUSION: In TROPHY, candesartan lowered BP but did not alter WBCC. Baseline
      WBCC did not predict incident hypertension. Our findings do not support the
      hypothesis that inflammation contributes to incident hypertension or that ARB
      treatment suppresses inflammation. The significant independent association of
      WBCC with baseline BMI and triglycerides is consistent with the evidence that
      obesity and insulin resistance are associated with inflammation. The findings
      highlight the importance of effective lifestyle modification in prehypertension
      to reduce inflammatory cardio-metabolic risk and suppress transition to
      hypertension.

PMID- 24275842
TI  - Total cholesterol and leptin concentrations are associated with prospective
      changes in systemic blood pressure in healthy pregnant women.
AB  - BACKGROUND: Lipids and leptin have been associated with high blood pressure (BP)
      levels during pregnancy. The aim was to evaluate the associations between serum
      lipids and leptin concentrations during the first trimester and longitudinal
      changes of SBP and DBP in healthy pregnancies. METHODS: Prospective cohort of
      pregnant women followed at a public healthcare center in Rio de Janeiro, Brazil.
      SBP and DBP were obtained at the <=13th, 20-26th, and 30-36th weeks of gestation
      and were the dependent variables. Serum lipids and plasma leptin concentrations
      were collected at 13 weeks or less of gestation and were the main independent
      variables. Statistical analyses included longitudinal linear mixed-effects
      regression models, with (beta) coefficients and their 95% confidence intervals
      (CI). RESULTS: Mean BPs were 109.8/66.9, 107.8/64.3, and 111.2/66.9  mmHg,
      respectively in the 1st, 2nd, and 3rd trimester. Multiple longitudinal
      regressions revealed that leisure time physical activity before pregnancy
      (beta(SBP) = -3.003, 95% CI = -5.034 to -0.971; beta(DBP) = -2.620, 95% CI = 
      4.177 to -1.064), baseline BMI (beta(SBP) = 4.003, 95% CI = 1.924-6.081;
      beta(DBP) = 1.862, 95% CI = 0.252-3.412), parity (beta(SBP) = -2.778, 95% CI = 
      4.627 to -0.929; beta(DBP) = -1.780, 95% CI = -3.168 to -0.392), and Homeostasis
      model of assessment-Insulin Resistance (HOMA-IR; beta(SBP) = 2.554, 95% CI =
      0.552-4.557; beta(DBP) = 2.962, 95% CI = 1.436-4.489) were the covariates
      independently associated with SBP and DBP changes. Monthly per-capita family
      income (beta(SBP) = -0.006, 95% CI = -0.010 to -0.001), total cholesterol
      (beta(SBP) = 2.094, 95% CI = 0.223-3.965), and leptin (beta(SBP) = 2.211, 95% CI
      = 0.159-4.263) were associated only with SBP changes. CONCLUSION: Serum total
      cholesterol and leptin concentrations, HOMA-IR, and BMI were positively
      associated with changes in BP during healthy pregnancies, whereas physical
      activity, parity, and family income were negatively associated.

PMID- 24275843
TI  - What format for hypertension guidelines: a challenge for authors and users.

PMID- 24275844
TI  - Iron(II)-catalysed [2+2+2] cycloaddition for pyridine ring construction.
AB  - We report a new, simple and air-stable iron(II) complex pre-catalyst for the
      synthesis of substituted pyridines via a [2+2+2] cycloaddition between diynes and
      nitrile derivatives.

PMID- 24275845
TI  - Improved outcomes using brain SPECT-guided treatment versus treatment-as-usual in
      community psychiatric outpatients: a retrospective case-control study.
AB  - Brain single-photon emission computed tomography (SPECT) scans indirectly show
      functional activity via measurement of regional cerebral blood flow. Thirty
      patients at a community-based psychiatric clinic underwent brain SPECT scans.
      Changes in scoring of before-treatment and after-treatment scans correlated well
      with changes in patient Global Assessment of Functioning (GAF) scores before
      treatment and after treatment. Patients were retrospectively matched with
      controls with similar diagnoses and pretreatment GAF scores, and those who
      underwent SPECT-guided treatment improved significantly more than the control
      patients. 

PMID- 24275846
TI  - Investigation of lattice dynamical and dielectric properties of MgO under high
      pressure by means of mid- and far-infrared spectroscopy.
AB  - We investigate the lattice dynamical and dielectric properties of MgO single
      crystals and powders by measurements in the mid- and far-infrared frequency
      region under high pressures, ranging up to 21.7 GPa. The shift of the restrahlen
      region is used to determine the pressure dependence of the transverse and
      longitudinal optical modes. The analysis of the refractive index in the mid- and
      far-infrared region allowed us to obtain the pressure behavior of the static and
      electronic dielectric constants. The transverse effective charge slowly decreases
      under high pressure, reflecting the stability of MgO. As a consequence, the
      pressure dependence of the static and electronic dielectric constants is mainly
      determined by the pressure dependence of the polar phonon frequency and Penn gap,
      resulting in a pronounced decrease of the former and a moderate decrease of the
      latter. 

PMID- 24275847
TI  - Safety of immunosuppressive drugs used as maintenance therapy in kidney
      transplantation: a systematic review and meta-analysis.
AB  - To evaluate the safety of regimens containing calcineurin inhibitors (CNI),
      proliferation signal inhibitors (TOR-I) and antimetabolites, we conducted a meta
      analysis of randomized clinical trials (RCTs) and observational studies. A total
      of 4,960 citations were identified in our electronic search and 14 additional
      articles were identified through hand searching. Forty-eight articles (11,432
      participants) from 42 studies (38 RCTs and four cohorts) met the inclusion
      criteria. Meta-analysis results revealed the following: (i) tacrolimus was
      associated with an increased risk for diabetes and lower risk of dyslipidemia,
      compared to cyclosporine; (ii) mycophenolate mofetil (MMF) was associated with
      increased risk for total infections, abdominal pain, diarrhea and vomiting,
      compared with azathioprine; (iii) sirolimus was associated with higher risk of
      anemia, diabetes, dyslipidemia, lymphoceles and withdrawal compared to tacrolimus
      or cyclosporine, and cyclosporine was associated with an increased risk of CMV
      infection; (iv) the combination of CNI with antimetabolites was associated with
      more adverse events than CNI alone; (v) TOR-I was related to more adverse events
      than MMF. The data observed in this meta-analysis are similar to those describe
      by others authors; thus, the choice of treatment must be made by the clinical
      staff based on specific patient characteristics. 

PMID- 24275848
TI  - MicroRNAs as Molecular Targets for Cancer Therapy: On the Modulation of MicroRNA
      Expression.
AB  - The discovery of small RNA molecules with the capacity to regulate messenger RNA
      (mRNA) stability and translation (and consequently protein synthesis) has
      revealed an additional level of post-transcriptional gene control. MicroRNAs
      (miRNAs), an evolutionarily conserved class of small noncoding RNAs that regulate
      gene expression post-transcriptionally by base pairing to complementary sequences
      in the 3' untranslated regions of target mRNAs, are part of this modulatory RNA
      network playing a pivotal role in cell fate. Functional studies indicate that
      miRNAs are involved in the regulation of almost every biological pathway, while
      changes in miRNA expression are associated with several human pathologies,
      including cancer. By targeting oncogenes and tumor suppressors, miRNAs have the
      ability to modulate key cellular processes that define the cell phenotype, making
      them highly promising therapeutic targets. Over the last few years, miRNA-based
      anti-cancer therapeutic approaches have been exploited, either alone or in
      combination with standard targeted therapies, aiming at enhancing tumor cell
      killing and, ideally, promoting tumor regression and disease remission. Here we
      provide an overview on the involvement of miRNAs in cancer pathology, emphasizing
      the mechanisms of miRNA regulation. Strategies for modulating miRNA expression
      are presented and illustrated with representative examples of their application
      in a therapeutic context. 

PMID- 24275849
TI  - The use of central nervous system active drugs during pregnancy.
AB  - CNS-active drugs are used relatively often during pregnancy. Use during early
      pregnancy may increase the risk of a congenital malformation; use during the
      later part of pregnancy may be associated with preterm birth, intrauterine growth
      disturbances and neonatal morbidity. There is also a possibility that drug
      exposure can affect brain development with long-term neuropsychological harm as a
      result. This paper summarizes the literature on such drugs used during pregnancy:
      opioids, anticonvulsants, drugs used for Parkinson's disease, neuroleptics,
      sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS
      active drugs. In addition to an overview of the literature, data from the Swedish
      Medical Birth Register (1996-2011) are presented. The exposure data are either
      based on midwife interviews towards the end of the first trimester or on linkage
      with a prescribed drug register. An association between malformations and
      maternal use of anticonvulsants and notably valproic acid is well known from the
      literature and also demonstrated in the present study. Some other associations
      between drug exposure and outcome were found. 

PMID- 24275850
TI  - Glibenclamide for the treatment of acute CNS injury.
AB  - First introduced into clinical practice in 1969, glibenclamide (US adopted name,
      glyburide) is known best for its use in the treatment of diabetes mellitus type
      2, where it is used to promote the release of insulin by blocking pancreatic KATP
      [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade,
      glibenclamide has received renewed attention due to its pleiotropic protective
      effects in acute CNS injury. Acting via inhibition of the recently characterized
      Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some
      cases, via brain KATP channels, glibenclamide has been shown to be beneficial in
      several clinically relevant rodent models of ischemic and hemorrhagic stroke,
      traumatic brain injury, spinal cord injury, neonatal encephalopathy of
      prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to
      reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death,
      it exerts potent anti-inflammatory effects and it promotes neurogenesis-all via
      inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently
      are underway. These recent findings, which implicate Sur1 in a number of acute
      pathological conditions involving the CNS, present new opportunities to use
      glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions
      that heretofore had few or no treatment options. 

PMID- 24275852
TI  - Loss of response to long-term infliximab therapy in children with Crohn's
      disease.
AB  - Secondary loss of response (LoR) often precludes further use of infliximab in
      children with Crohn's disease. Immunomodulators may reduce the incidence of LoR
      but their combination with infliximab presents safety concerns. We aimed to
      determine the long-term durability of infliximab response in paediatric Crohn's,
      effect of immunomodulators on LoR, and secondarily the effect of infliximab on
      growth. We retrospectively audited patients on maintenance infliximab at a single
      centre. Data included height and weight, Paediatric Crohn's Disease Activity
      Index (PCDAI), and immunomodulator use. 71 children (32% female, mean age 14.4
      years) had been commenced on maintenance infliximab before July 2011. 89% had
      been on immunomodulators concurrently with infliximab. LoR occurred in 20 (28%),
      with a median time to LoR of 4.31 years. LoR was significantly increased in
      children who did not enter remission (PCDAI <= 10) after induction (p < 0.05).
      LoR occurred more frequently in the 72% who ceased immunomodulators, but this
      failed to reach statistical significance (p = 0.300). Height and weight SDS
      improved significantly on infliximab. Infliximab is a durable long-term therapy
      for paediatric Crohn's refractory to conventional therapy. A large-magnitude
      increase in the rate of loss of response after immunomodulator cessation was not
      observed. 

PMID- 24275851
TI  - Drug repositioning: an opportunity to develop novel treatments for Alzheimer's
      disease.
AB  - Alzheimer's Disease (AD) is the most common cause of dementia, affecting
      approximately two thirds of the 35 million people worldwide with the condition.
      Despite this, effective treatments are lacking, and there are no drugs that
      elicit disease modifying effects to improve outcome. There is an urgent need to
      develop and evaluate more effective pharmacological treatments. Drug
      repositioning offers an exciting opportunity to repurpose existing licensed
      treatments for use in AD, with the benefit of providing a far more rapid route to
      the clinic than through novel drug discovery approaches. This review outlines the
      current most promising candidates for repositioning in AD, their supporting
      evidence and their progress through trials to date. Furthermore, it begins to
      explore the potential of new transcriptomic and microarray techniques to consider
      the future of drug repositioning as a viable approach to drug discovery. 

PMID- 24275853
TI  - Sustaining cancer through addictive ectopic gene activation.
AB  - PURPOSE OF REVIEW: Systematic genetic and epigenetic alterations occurring in
      almost all cancer cells result in the ectopic expression of a variety of tissue
      specific potent regulatory factors. This review sheds light on a new aspect of
      cancer based on the integration of the 'out of context' activity of tissue
      restricted genes into the biology of cancer cells. RECENT FINDINGS: A systematic
      screen for the ectopic activation of tissue-restricted genes in a variety of
      cancers has revealed that many normally silent genes are expressed in tumours of
      all origins. This aberrant gene activation not only could be used as a source of
      biomarkers, but also, in several cases, reveals clear oncogenic mechanisms
      associated with the corresponding ectopically expressed factors. SUMMARY: The
      characteristic of all cancer cells, which systematically reprogram tissue
      specific gene expression and activate silent genes, can be exploited to develop
      new anticancer strategies aiming at the detection of malignant states, the
      prediction of their evolution and drug sensitivity and the discovery of new
      therapeutic approaches.

PMID- 24275854
TI  - Reactivation of p53 as therapeutic intervention for malignant melanoma.
AB  - PURPOSE OF REVIEW: Targeted therapy of malignant melanoma recently experienced
      remarkable advances with gene mutation-based therapies with signaling pathway
      inhibitors (kinase inhibitors). The treatments prolong patients' survival, but in
      general resistance is acquired and progression of disease occurs. Therefore,
      additional therapeutic targets are desperately needed. RECENT FINDINGS: The p53
      tumor suppressor gene is rarely mutated in melanoma, but its functional
      attenuation is needed for tumor development. Recently, it was found that the
      essential p53 inhibitor Mdmx is very frequently overexpressed in melanoma. Mdmx
      displays both p53-dependent and p53-independent oncogenic effects needed for
      melanoma growth SUMMARY: Current melanoma therapy based upon kinase inhibitors
      shows robust initial clinical effect, but the duration of effect is limited.
      Inactivation of Mdmx in melanoma inhibits tumor growth also of kinase-inhibitor
      resistant tumors. An observed synergistic effect of kinase-inhibition and Mdmx
      targeting can lead to better and more durable treatment of melanoma patients.

PMID- 24275856
TI  - Glatiramer acetate ameliorates experimental autoimmune neuritis.
AB  - Glatiramer acetate (GA) is one of the first-line disease-modifying medications
      that have been approved for the treatment of multiple sclerosis via immune
      modulatory mechanisms. However, it remains unclear whether the immunomodulation
      effect of GA is central nervous system (CNS) antigen specific. Here, we explored
      the mechanism of action of GA by subcutaneously injecting GA in experimental
      autoimmune neuritis (EAN) rats, an animal model for Guillain-Barre syndrome
      (GBS). Clinical, electrophysiological and histological findings showed that
      neurological deficits, demyelination and axonal injury of sciatic nerves were all
      significantly attenuated in Lewis rats when GA was administered before
      immunization with peripheral nervous system antigen P0. Our results further
      demonstrated that GA treatment inhibited either P0 or myelin basic protein (MBP)
      (CNS antigen)-stimulated auto-immune T-cell proliferation in vitro. GA
      administrated at 10 days after induction of EAN when neurological sign became
      apparent also ameliorated the severity of disease, inhibited T-cell response to
      P0 and MBP and induced shift of proinflammatory and immune modulatory cytokines.
      Collectively, our findings suggested that GA attenuated neurological deficits in
      EAN rats and that the immune modulatory mechanisms of GA were not CNS antigen
      specific. 

PMID- 24275859
TI  - Comparison of hamstring tendon and patellar tendon grafts in anterior cruciate
      ligament reconstruction in a nationwide population-based cohort study: results
      from the danish registry of knee ligament reconstruction.
AB  - BACKGROUND: The choice of graft for anterior cruciate ligament reconstruction
      (ACLR) remains controversial, and despite numerous studies, there is still an
      ongoing debate on this topic. The 2 most widely used grafts are the hamstring
      tendon and patellar tendon. HYPOTHESIS: In this study, we hypothesized that the
      revision rate after primary ACLR is greater when using hamstring tendon grafts
      compared with patellar tendon grafts. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: From the nationwide population-based Danish Knee Ligament
      Reconstruction Registry, we identified all primary ACLR procedures (n = 13,647)
      performed in Denmark between July 2005 and December 2011. The end point was
      revision ACLR. As other end points, we used objective measurements and patient
      reported outcome scores. Revision rates and relative risk estimates for revision
      ACLR were calculated using Cox multiple regression. RESULTS: The use of hamstring
      tendon grafts increased from 68% in 2005 to 85% in 2011. The cumulative revision
      rates for hamstring tendon grafts at 1 and 5 years were 0.65% (95% confidence
      interval [CI], 0.51%-0.82%) and 4.45% (95% CI, 3.94%-5.01%), respectively. For
      patellar tendon grafts, the revision rate was 0.16% (95% CI, 0.05%-0.50%) at 1
      year and 3.03% (95% CI, 2.27%-4.05%) at 5 years. The adjusted overall relative
      risk of revision surgery in the hamstring tendon group compared with the patellar
      tendon group was 1.41 (95% CI, 1.03-1.92), and the adjusted relative risk of
      undergoing revision surgery performed after 1 and 5 years was 3.82 (95% CI, 1.20
      12.2) and 1.90 (95% CI, 0.43-8.40), respectively. CONCLUSION: In this population
      based study, the use of hamstring tendon grafts in ACLR was associated with an
      increased risk of revision compared with patellar tendon grafts, in particular
      during the first year after surgery. These results demonstrate that both
      hamstring and patellar tendon grafts reveal good results after ACLR and suggest
      that graft selection should be based on an individual evaluation of patient
      demands and graft morbidity.

PMID- 24275855
TI  - Contributions of metabolic dysregulation and inflammation to nonalcoholic
      steatohepatitis, hepatic fibrosis, and cancer.
AB  - PURPOSE OF REVIEW: We review accumulating evidence that nonalcoholic
      steatohepatitis (NASH), a more advanced form of nonalcoholic fatty liver disease
      (NAFLD), predisposes patients to the risk of developing hepatocellular carcinoma
      (HCC), and we summarize recent advances in the elucidation of cancer-promoting
      pathways in NASH. We highlight the potential role of progenitor cells and hepatic
      stellate cells (HSCs) in promoting the early events that could culminate in
      cancer, as well as the emerging contribution of the gut-liver axis in promoting
      inflammation, senescence, and tumor growth in NASH and HCC. Finally, we review
      the role of bile acid receptors, vitamin D, and protective cellular pathways such
      as autophagy. RECENT FINDINGS: Studies have recently uncovered roles for gut
      microbiota, bile acid receptors and vitamin D in regulating the progression from
      NAFLD to HCC. Intriguing findings linking senescence and autophagy in hepatic
      stellate cells to HCC have also been discovered, as well as a link between
      dysregulated progenitor cell regulation and HCC. SUMMARY: NAFLD is the most
      common cause of chronic liver disease in the United States and Western Europe.
      The lack of definitive mechanisms underlying development of NASH among patients
      with NAFLD and its progression to HCC limit diagnosis and management, but new
      findings are paving the way for better biomarkers and therapies.

PMID- 24275857
TI  - Nicotinamide phosphoribosyltransferase (NAMPT) activity is essential for survival
      of resting lymphocytes.
AB  - NAD biosynthesis is emerging as a key regulator of immune cell functions.
      Accordingly, inhibitors of the NAD-synthesizing enzyme nicotinamide
      phosphoribosyltransferase (NAMPT) have anti-inflammatory effects, counteract
      hematological malignancies and are being tested in clinical trials. Still, their
      effect on different cell types still waits to be fully investigated. Here we show
      that the NAMPT inhibitor FK866 induces NAD depletion in various mouse organs but
      selectively causes dramatic atrophy of the spleen red pulp. Accordingly, in
      cultured mouse lymphocytes exposed to FK866, NAD contents drop to 50% of basal
      values within 2 days, a condition sufficient to prompt complete cell death.
      Cultures of human lymphocytes are more resistant to FK866 and sustain a 50% NAD
      reduction for 5 days before dying. Death of both cell types can be prevented by
      different NAD precursors, indicating critical NAD homeostasis in lymphocytes.
      Indeed, inhibition of the NAD-consuming enzyme poly(ADP-ribose) polimerase-1
      suffices to prevent FK866-induced NAD depletion and death of both lymphocyte
      types. Poly(ADP-ribose) polymerase-1-null lymphocytes also undergo lower NAD
      depletion and reduced cell death when exposed to the drug. At variance with other
      cell types, neither apoptosis nor autophagy are exclusively responsible for
      lymphocyte death by FK866, consistent with a general impairment of lymphocyte
      homeostasis following NAD depletion. Data demonstrate a unique sensitivity of
      resting lymphocytes to NAD-depleting agents, providing new hints of relevance to
      lymphocyte biology and therapeutic interventions with NAMPT inhibitors. 

PMID- 24275860
TI  - Relationship between isokinetic strength and tibiofemoral joint space width
      changes after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: It has been hypothesized that quadriceps muscle weakness is directly
      associated with the onset and progression of posttraumatic osteoarthritis after
      anterior cruciate ligament (ACL) injury and reconstruction (ACLR). This
      relationship, however, has not been studied with a prospective approach that
      includes the use of tibiofemoral joint space width difference (JSW-D)
      measurements to characterize the onset of posttraumatic osteoarthritis before the
      clinical manifestation of the disease. PURPOSE: To assess the relationship
      between thigh muscle strength and JSW-D at presurgery baseline and at 1- and 4
      year follow-up after ACLR compared with healthy, noninjured participants of
      similar sex, age, body mass index, and activity level. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: A total of 39 unilateral ACL-injured
      patients and 32 healthy controls were followed prospectively. During each follow
      up, JSW, isokinetic knee strength, single-legged hop, and clinical- and patient
      oriented outcomes were assessed. At final follow-up, ACL-injured participants who
      had JSW-D values (considered as the injured minus normal knee) that were less
      than the 95% confidence interval of controls were considered to be in the ACLR
      narrow group, while those with JSW-D values that fell within the confidence
      intervals were in the ACLR-normal group. Relationships were evaluated between
      ACLR groups and controls via multilevel regression, as well as Kruskal-Wallis
      tests for between-group comparisons at 4-year follow-up. RESULTS: At 4-year
      follow-up, 30 participants (79%) were in the ACLR-normal group and 8 (21%) were
      in the ACLR-narrow group. At baseline, the extension, flexion, and
      extension/flexion ratio strength values for both ACLR groups were significantly
      lower than those of controls (P <= .05), while the ACLR-narrow group had
      significantly lower extension strength at 60 and 180 deg/s (P = .04 and .03,
      respectively), as well as extension/flexion ratio at 60 deg/s (P = .04) in
      comparison with the ACL-normal group. At 4-year follow-up, 60 deg/s extension
      strength deficits persisted in the ACLR-narrow group compared with controls and
      ACLR-normal participants (P = .01 and .04, respectively). Flexion strength at 180
      and 300 deg/s was also significantly lower in the ACLR-narrow group compared with
      ACLR-normal (P = .02 and .04, respectively), as was single-legged hop distance (P
      = .04). CONCLUSION: Strength deficits present within months after ACL injury and
      persist through 4 years after ACLR in participants with significantly narrowed
      JSW-D, compared with ACLR participants with normal JSW-D and controls. This study
      revealed a significant relationship between quadriceps strength loss that
      occurred soon after injury and JSW narrowing.

PMID- 24275861
TI  - The effect of femoral tunnel position and graft tension on patellar contact
      mechanics and kinematics after medial patellofemoral ligament reconstruction.
AB  - BACKGROUND: An incorrect femoral tunnel position or inappropriate graft
      tensioning during medial patellofemoral ligament (MPFL) reconstruction may cause
      altered patellofemoral joint kinematics and contact mechanics, potentially
      resulting in pain and joint degeneration. HYPOTHESIS: Nonanatomic positioning of
      the tunnel or graft overtensioning during MPFL reconstruction will have an
      adverse effect on patellar tracking and patellofemoral joint contact mechanics.
      STUDY DESIGN: Controlled laboratory study. METHODS: Eight fresh-frozen cadaveric
      knees were placed on a customized testing rig, with the femur fixed and the tibia
      mobile through 90 degrees  of flexion. Individual heads of the quadriceps muscle
      and the iliotibial band were separated and loaded with 205 N in anatomic
      directions using a system of cables and weights. Patellofemoral contact pressures
      and patellar tracking were measured through the flexion range at 10 degrees 
      intervals using Tekscan pressure-sensitive film inserted between the patella and
      trochlea and an optical tracking system. The MPFL was transected and then
      reconstructed using a double-strand gracilis tendon graft. Pressures and
      kinematics were recorded for reconstructions with the graft positioned in
      anatomic, proximal, and distal tunnel positions. Measurements were then repeated
      with an anatomic tunnel and graft tension of 2 N, 10 N, and 30 N, fixed at 3
      different flexion angles of 0 degrees , 30 degrees , and 60 degrees . Statistical
      analysis was undertaken using repeated-measures analysis of variance, Bonferroni
      post hoc analysis, and paired t tests. RESULTS: For a graft tensioned to 2 N,
      anatomically positioned MPFL reconstruction restored intact medial and lateral
      joint contact pressures and patellar tracking (P > .05), but femoral tunnels
      positioned proximal or distal to the anatomic origin resulted in significant
      increases in peak and mean medial pressures and medial patellar tilt during knee
      flexion or extension, respectively (P < .05). Grafts tensioned with 10 N or 30 N
      also caused significant increases in medial pressure and tilt. Graft fixation at
      30 degrees  or 60 degrees  restored all measures to intact values (P > .05), but
      fixation at 0 degrees  caused significant increases (P < .05) in medial joint
      contact pressures compared with intact knees. CONCLUSION: Anatomically positioned
      reconstruction with 2-N tension fixed at 30 degrees  or 60 degrees  of knee
      flexion restored joint contact pressures and tracking. However, graft
      overtensioning or femoral tunnels positioned too proximal or distal caused
      significantly elevated medial joint contact pressures and increased medial
      patellar tilting. The importance of a correct femoral tunnel position and graft
      tensioning in restoring normal patellofemoral joint kinematics and articular
      cartilage contact stresses is therefore evident. CLINICAL RELEVANCE: A
      malpositioned femoral tunnel or overtensioned graft during MPFL reconstruction
      resulted in increased medial contact pressures and patellar tilting. This may
      lead to adverse outcomes such as early degenerative joint changes or pain if
      occurring in a clinical population.

PMID- 24275862
TI  - Epidemiology of primary anterior shoulder dislocation requiring closed reduction
      in Ontario, Canada.
AB  - BACKGROUND: There is a lack of high-quality population-based literature
      describing the epidemiology of primary anterior shoulder dislocation. PURPOSE: To
      (1) calculate the incidence density rate (IDR) of primary anterior shoulder
      dislocation requiring closed reduction (CR; "index event") in the general
      population and demographic subgroups, and (2) determine the rate of and risk
      factors for repeat shoulder CR. STUDY DESIGN: Cohort study (prognosis); Level of
      evidence, 2. METHODS: All patients who underwent shoulder CR by a physician in
      Ontario between April 2002 and September 2010 were identified with administrative
      databases. Exclusion criteria included age <16 and >70 years, posterior
      dislocation, and prior shoulder dislocation or surgery. Index event IDR was
      calculated for all populations/subgroups, and IDR comparisons were made. Repeat
      shoulder CR was sought until September 2012. Risk factors for repeat shoulder CR
      were identified with a Prentice, Williams, and Peterson proportional hazards
      model. RESULTS: There were 20,719 persons (median age, 35 years; 74.3% male) who
      underwent a shoulder CR after a primary anterior shoulder dislocation
      (23.1/100,000 person-years). The IDR was highest among young males (98.3/100,000
      person-years). A total of 3940 (19%) patients underwent repeat shoulder CR after
      a median of 0.9 years, of which 41.7% were <=20 years of age. Less than two
      thirds of all first repeat shoulder CR events occurred within 2 years; in fact,
      95% occurred within 5 years. The risk of repeat shoulder CR was lowest if the
      primary reduction had been performed by an orthopaedic surgeon (hazard ratio
      [HR], 0.76; 95% CI: 0.64, 0.90; P = .002) or was associated with a humeral
      tuberosity fracture (HR, 0.71; CI, 0.53, 0.95; P = .02). Older age (HR, 0.97; CI,
      0.97, 0.98; P < .0001) and higher medical comorbidity score (HR, 0.92; CI, 0.87,
      0.98; P = .009) were also protective. Risk was highest among males (HR, 1.26; CI,
      1.16, 1.36; P < .0001) and patients from low-income neighborhoods (HR, 1.23; CI,
      1.13, 1.34; P < .0001). CONCLUSION: Young male patients have the highest
      incidence of primary anterior shoulder dislocation requiring CR and the greatest
      risk of repeat shoulder CR. Patient, provider, and injury factors all influence
      repeat shoulder CR risk. A comprehensive understanding of the epidemiology of
      primary anterior shoulder dislocation will aid management decisions and injury
      prevention initiatives.

PMID- 24275864
TI  - Anterior talofibular ligament ruptures, part 1: biomechanical comparison of
      augmented Brostrom repair techniques with the intact anterior talofibular
      ligament.
AB  - BACKGROUND: The concept of utilizing nonabsorbable suture tape fixed directly to
      bone to augment Brostrom repairs of the anterior talofibular ligament (ATFL) has
      been proposed. No biomechanical studies of this technique are available.
      HYPOTHESIS: We hypothesized that suture tape augmentation alone and Brostrom
      repair with suture tape augmentation would have similar biomechanical properties
      to the intact ATFL at time zero in a cadaveric model. STUDY DESIGN: Controlled
      laboratory study. METHODS: Eighteen fresh-frozen cadaveric ankles were randomized
      into 3 groups of 6 specimens each: (1) intact ATFL, (2) suture tape augmentation,
      and (3) Brostrom repair with suture tape augmentation. The specimens were loaded
      to failure to determine the strength and stiffness of each construct. RESULTS:
      The mean ultimate load to failure of suture tape augmentation (315.5 +/- 66.8 N)
      was significantly higher than that of the intact ATFL (154.0 +/- 63.7 N) (P =
      .017). The mean ultimate load of the Brostrom repair with suture tape
      augmentation (250.8 +/- 122.7 N) was not significantly different from that of the
      intact ATFL. The mean stiffness of augmentation alone (31.4 +/- 9.9 N/mm) was
      significantly higher than that of the intact ATFL (14.5 +/- 4.4 N/mm) (P = .008).
      The mean stiffness of the Brostrom repair with augmentation (21.1 +/- 9.1 N/mm)
      was not significantly different from that of the intact ATFL. CONCLUSION: The
      ATFL with suture tape augmentation is at least as strong and stiff as the native
      ATFL at time zero in a fresh-frozen cadaveric model. CLINICAL RELEVANCE: The
      Brostrom repair for lateral ankle ligament ruptures is often unsuccessful in
      circumstances of poor tissue quality. Augmentations, such as with suture tape,
      have been proposed for these situations. Suture tape used alone or in combination
      with the Brostrom repair provided increased strength and stiffness compared with
      the standard Brostrom repair, which produced an immediate strength of less than
      50% of the intact ATFL. Adding strength to the Brostrom repair may be valuable in
      patients with generalized ligamentous laxity, in large patients or elite
      athletes, or when graft reconstruction is not feasible.

PMID- 24275863
TI  - Diagnostic value of knee arthrometry in the prediction of anterior cruciate
      ligament strain during landing.
AB  - BACKGROUND: Previous studies have indicated that higher knee joint laxity may be
      indicative of an increased risk of anterior cruciate ligament (ACL) injuries.
      Despite the frequent clinical use of knee arthrometry in the evaluation of knee
      laxity, little data exist to correlate instrumented laxity measures and ACL
      strain during dynamic high-risk activities. Purpose/ HYPOTHESES: The purpose of
      this study was to evaluate the relationships between ACL strain and anterior knee
      laxity measurements using arthrometry during both a drawer test and simulated
      bipedal landing (as an identified high-risk injurious task). We hypothesized that
      a high correlation exists between dynamic ACL strain and passive arthrometry
      displacement. The secondary hypothesis was that anterior knee laxity quantified
      by knee arthrometry is a valid predictor of injury risk such that specimens with
      greater anterior knee laxity would demonstrate increased levels of peak ACL
      strain during landing. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty
      cadaveric lower limbs (mean age, 46 +/- 6 years; 10 female and 10 male) were
      tested using a CompuKT knee arthrometer to measure knee joint laxity. Each
      specimen was tested under 4 continuous cycles of anterior-posterior shear force
      (+/-134 N) applied to the tibial tubercle. To quantify ACL strain, a differential
      variable reluctance transducer (DVRT) was arthroscopically placed on the ACL
      (anteromedial bundle), and specimens were retested. Subsequently, bipedal landing
      from 30 cm was simulated in a subset of 14 specimens (mean age, 45 +/- 6 years; 6
      female and 8 male) using a novel custom-designed drop stand. Changes in joint
      laxity and ACL strain under applied anterior shear force were statistically
      analyzed using paired sample t tests and analysis of variance. Multiple linear
      regression analyses were conducted to determine the relationship between anterior
      shear force, anterior tibial translation, and ACL strain. RESULTS: During
      simulated drawer tests, 134 N of applied anterior shear load produced a mean peak
      anterior tibial translation of 3.1 +/- 1.1 mm and a mean peak ACL strain of 4.9%
      +/- 4.3%. Anterior shear load was a significant determinant of anterior tibial
      translation (P < .0005) and peak ACL strain (P = .04). A significant correlation
      (r = 0.52, P < .0005) was observed between anterior tibial translation and ACL
      strain. Cadaveric simulations of landing produced a mean axial impact load of
      4070 +/- 732 N. Simulated landing significantly increased the mean peak anterior
      tibial translation to 10.4 +/- 3.5 mm and the mean peak ACL strain to 6.8% +/-
      2.8% (P < .0005) compared with the prelanding condition. Significant correlations
      were observed between peak ACL strain during simulated landing and anterior
      tibial translation quantified by knee arthrometry. CONCLUSION: Our first
      hypothesis is supported by a significant correlation between arthrometry
      displacement collected during laxity tests and concurrent ACL strain calculated
      from DVRT measurements. Experimental findings also support our second hypothesis
      that instrumented measures of anterior knee laxity predict peak ACL strain during
      landing, while specimens with greater knee laxity demonstrated higher levels of
      peak ACL strain during landing. CLINICAL RELEVANCE: The current findings
      highlight the importance of instrumented anterior knee laxity assessments as a
      potential indicator of the risk of ACL injuries in addition to its clinical
      utility in the evaluation of ACL integrity.

PMID- 24275866
TI  - Somatic hybridization in Nicotiana: Restoration of photoautotrophy to an albino
      mutant with defective plastids.
AB  - Protoplasts of a cytoplasmic albino mutant of Nicotiana tabacum L. characterized
      by a deficient chloroplast genome were fused with protoplasts of a nitrate
      reductase deficient mutant (NR(-)) of N. tabacum. Somatic hybrids were obtained
      where the genome of the NR(-) mutant was complemented by the cytoplasmic albino
      mutant which could synthesize an active nitrate reductase, and the chlorophyll
      deficiency in the albino mutant was restored by the chloroplasts from the NR(-)
      mutant. Cybrids were also obtained in which the deficient plastids of the
      cytoplasmic albino mutant were replaced by normal chloroplasts from the NR(-)
      mutant. The system used permitted a simple selection of the hybrids and the
      cybrids. The NR(-) mutant was excluded at the cellular level by transfer of the
      cells to medium deficient in reduced nitrogen. The cytoplasmic albino mutant grew
      well on the selective nitrate medium. However, during callus formation, clear
      differences in the morphology and pigmentation of the calli were found which
      permitted selection for photoautotrophy at the callus level. The hybrid or cybrid
      nature of the plants was confirmed by examination of their morphology and
      chromosome number. Although the fusion partners come from the same species, only
      one plant showed the white-green variegated pattern typical of that of the
      cytoplasmic albino parent, indicating that segregation of plastids occurred
      during development of the calli and regeneration of the plants. 

PMID- 24275865
TI  - KIFC3 promotes mitotic progression and integrity of the central spindle in
      cytokinesis.
AB  - Kinesin-14 motor proteins play a variety of roles during metaphase and anaphase.
      However, it is not known whether members of this family of motors also
      participate in the dramatic changes in mitotic spindle organization during the
      transition from telophase to cytokinesis. We have identified the minus-end
      directed motor, KIFC3, as an important contributor to central bridge morphology
      at this stage. KIFC3's unique motor-dependent localization at the central bridge
      allows it to congress microtubules, promoting efficient progress through
      cytokinesis. Conversely, when KIFC3 function is perturbed, abscission is delayed,
      and the central bridge is both widened and extended. Examination of KIFC3 on
      growing microtubules in interphase indicates that it caps microtubules released
      from the centrosome, both in the region of the centrosome and in the cell
      periphery. In line with other kinesin-14 family members, KIFC3 may guide free
      microtubules to their destination at the bridge and/or may slide and crosslink
      central bridge microtubules in order to stage the cells for abscission. 

PMID- 24275867
TI  - Somatic hybridization in Nicotiana: Segregation of organellar traits among hybrid
      and cybrid plants.
AB  - Protoplasts from a nitrate reductase-deficient mutant of Nicotiana tabacum L.
      were fused with protoplasts from a stamen-less, cytoplasmically malesterile
      cultivar of tobacco containing the cytoplasm from N. suaveolens Lehm. Plants were
      regenerated from the fused protoplasts and characterized with respect to stamen
      development, chromosome number, and chloroplast composition. Of 29 regenerated
      plants, stamen production was restored in 26 plants and pollen production in 22.
      One plant was male sterile and two plants have never flowered. Analysis of the
      electrophoretic mobility of ribulose-1,5-bisphosphate carboxylase (RuBPcase)
      showed that 19 of the plants contained RuBPcase of the N. suaveolens type, six
      plants contained enzyme of the N. tabacum type, and four plants contained both
      types. Analysis of resistance to tentoxin in seedlings from 20 of the plants
      demonstrated that 14 had N. suaveolens-type chloroplasts, three had N. tabacum
      type, and three contained both types. Many of the plants which produced stamens
      and pollen still contained chloroplasts of the N. suaveolens type. Thus, the
      trait of cytoplasmic male sterility in tobacco is not an expression of the type
      of chloroplast genetic material. 

PMID- 24275868
TI  - Amino-acid transport into cultured tobacco cells : III. Arginine transport.
AB  - Arginine transport in suspension-cultured cells of Nicotiana tabacum L. cv.
      Wisconsin-38 was investigated. Cells that were preincubated in the presence of
      Ca(2+) for 6 h prior to transport exhibited stimulated transport rates. After the
      preincubation treatment, initial rates of uptake were constant for at least 45
      min. Arginine accumulated in the cells against a concentration gradient; this
      accumulation was not the result of exchange diffusion. Arginine uptake over a
      concentration range of 2.5 MUM to 1 mM was characterized by simple Michaelis
      Menten kinetics with a Km of 0.1 mM and a Vmax of 9,000 nmol g(-1) fresh weight
      h(-1). Transport was inhibited by several compounds including carbonylcyanide-m
      chlorophenylhydrazone, 2,4-dinitrophenol, N,N'-dicyclohexylcarbodiimide, and N
      ethylmaleimide. Inhibition by these compounds was not the result of increased
      efflux resulting from membrane damage. A variety of amino acids and analogs, with
      the exception of D-arginine, inhibited transport, indicating that arginine
      transport was mediated by a general L-aminoacid permease. Competition experiments
      indicated that arginine and lysine exhibited cross-competition for transport,
      with Ki values similar to respective Km values. Arginine transport and low
      affinity lysine transport are probably mediated by the same system in these
      cells. 

PMID- 24275869
TI  - Synthesis of acyl-CoAs by isolated spinach chloroplasts in relation to added CoA
      and ATP.
AB  - The kinetics of incorporation of [2-(14)C] acetate into lipids and acyl-CoAs in
      relation to added CoA and ATP by isolated spinach chloroplasts have been
      examined. The effect of the concentration of these cofactors on lipid and acyl
      CoA synthesis was also studied. In the absence of cofactors, or when only one was
      present, the incorporation was very low and went mainly into lipids. When both
      cofactors were present a strong stimulation of both activities occurred. After 25
      min, acyl-CoAs were more strongly labeled than lipids and both activities
      continued linearly for at least 60 min. 

PMID- 24275870
TI  - Increase of protein synthesis after isolation in dormant and afterripened
      Agrostemma githago L. embryos.
AB  - Isolated embryos are more suitable for in vivo study of protein synthesis than
      non-isolated embryos because, after isolation, the uptake of labeled amino acids
      is about 1000 times higher. However, isolation also stimulates protein synthesis:
      Up to 4 h after isolation, the capacity to incorporate labeled amino acids
      increased 7 times. Therefore, data on incorporation obtained with isolated
      embryos cannot be extended to non-isolated embryos. The increase of protein
      synthesis was not due to synthesis of specific proteins, but was a general
      increase. Furthermore, ripening, dormant, and afterripened embryos showed the
      same degree of increase. Isolation therefore stimulates protein synthesis
      nonspecifically. When embryos were kept under anaerobic conditions after
      isolation, protein synthesis did not increase. Therefore, higher oxygen
      consumption after removal of the seedcoat is probably the cause of the higher
      incorporation capacity. Furthermore, the activation of protein synthesis lagged
      several hours behind the increase of oxygen consumption. 

PMID- 24275871
TI  - Endogenous plant hormones of the broad bean, Vicia faba L. (-)-jasmonic acid, a
      plant growth inhibitor in pericarp.
AB  - (-)-Jasmonic acid was identified as a plant growth inhibitor of the pericarp of
      Vicia faba by means of gas-liquid chromatography, high resolution mass
      spectrometry, (1)H-nuclear magnetic resonance ((1)H-NMR), and (13)C-NMR.
      Additionally, the pericarp contains very small amounts of abscisic acid (ABA) and
      4'-dihydrophaseic acid. The highest level of jasmonic acid was reached prior to
      full pericarp length. This amount (3 MUg g(-1) fresh weight) is similar to the
      maximal ABA content in the developing seed. Jasmonic acid is a plant growth
      inhibitor possessing a relative activity in the wheat seedling bioassay of 1
      2.5%, compared to ABA. Contrary to ABA, jasmonic acid does not cause retardation
      of leaf emergence. The possible physiological role of jasmonic acid in the
      pericarp is discussed and compared with the assumed function of ABA in developing
      seeds. 

PMID- 24275872
TI  - Chloroplast DNA of Acetabularia mediterranea: Cell cycle related changes in
      distribution.
AB  - Chloroplast DNA (cpDNA) distribution in the giant unicellular, uninucleate alga
      Acetabularia mediterranea was analyzed with the DNA-specific fluorochrome 4'6
      diamidino-2-phenylindole (DAPI) at various stages of the cell cycle. The number
      of chloroplasts exhibiting DNA/DAPI fluorescence changes during the cell's
      developmental cycle: (1) all chloroplasts in germlings contain DNA; (2) the
      number of plastids with DNA declines during polar growth of the vegetative cell;
      (3) it increases again prior to the transition from the vegetative to the
      generative phase; (4) several nucleoids of low fluorescence intensity are present
      in the chloroplasts of the gametes. The temporal distribution of the number of
      chloroplasts with DNA appears to be linked to the different mode of chloroplast
      division and growth during the various stages of development. The chloroplast
      cycle in relation to the cell cycle is discussed. 

PMID- 24275873
TI  - Phytochrome-mediated effects of near-ultraviolet radiation in the induction of
      flowering in etiolated Lemna paucicostata T-101, a short-day plant.
AB  - Induction of flowering of etiolated Lemna paucicostata Hegelm. T-101, a short-day
      plant, was inhibited by far-red (FR) or blue light (BL) applied at the beginning
      of a 72-h inductive dark period which was followed by two short days. In either
      case the inhibition was reversed by a subsequent exposure of the plants to near
      ultraviolet radiation (NUV), with a peak of effectiveness near 380 nm. Inhibition
      by BL or FR and its reversion by NUV are repeatable, i.e., NUV is acting in these
      photoresponses like red light although with much lower effectiveness. Thus, it is
      considered that NUV acts through phytochrome and no specific BL and NUV
      photoreceptor is involved in photocontrol of floral induction on this plant. 

PMID- 24275874
TI  - Synthesis of ribosomal RNA in ribosome-deficient plastids of the mutant
      "albostrians" of Hordeum vulgare L.
AB  - The nuclear gene-induced plastome mutant "albostrians" of Hordeum vulgare L. is
      characterized by a plastid ribosome-deficiency. This ribosome deficiency could be
      caused by the lack of or a defect in chloroplast RNA polymerase. However in our
      investigations we found an activity of chloroplast RNA polymerase in wild-type
      and mutant leaves of "albostrians" barley by (1) electron microscopic autoradio
      graphy after in vivo labelling of RNA, (2) determination of RNA polymerase
      activity in isolated plastids, and (3) characterization of the newly synthesized
      RNA by electrophoresis in polyacrylamide gels. The genes of 23S and 16S rRNA are
      transcribed in mutant plastids and the RNAs are processed. From these results we
      conclude that the enzymes involved in transcription and processing of chloroplast
      rRNA are synthesized on cytoplasmic ribosomes and that the plastid ribosome
      deficiency in albostrians barley is probably not caused by a defective
      chloroplast DNA dependent RNA polymerase or by a mutation in the genes of 23S and
      16S chloroplast rRNA. 

PMID- 24275875
TI  - Light quantity and quality interactions in the control of elongation growth in
      light-grown Chenopodium rubrum L. seedlings.
AB  - The spectral control of hypocotyl elongation in light-grown Chenopodium rubrum L.
      seedlings has been studied. The results showed that although the seedlings
      responded to changes in the quantity of combined red and far-red radiation, they
      were also very sensitive to changes in the quantity of blue radiation reaching
      the plant. Altering the proportion of red: far-red radiation in broad waveband
      white light caused marked differences in hypocotyl extension. Comparison of the
      responses of green and chlorophyll-free seedlings indicated no qualitative
      difference in the response to any of the light sources used, although
      photosynthetically incompetent plants were more sensitive to all wavelengths.
      Blue light was found to act primarily of a photoreceptor which is different from
      phytochrome. It is concluded that hypocotyl extension rate in vegetation shade is
      photoregulated by the quantity of blue light and the proportion of red: far-red
      radiation. In neutral shade, such as that caused by stones or overlying soil,
      hypocotyl extension appears to be regulated primarily by the quantity of light in
      the blue waveband and secondarily by the quantity of light in the red and far-red
      wavebands. 

PMID- 24275876
TI  - Levels of indole-3-acetic acid in intact and decapitated coleoptiles as
      determined by a specific and highly sensitive solid-phase enzyme immunoassay.
AB  - A specific solid-phase enzyme immunoassay for the detection of as little as 3-4
      pg of indole-3-acetic acid (IAA) is described. The assay involves minimal
      procedural efforts and requires only standard laboratory equipment. Up to 50
      samples in triplicate, processed simultaneously, can be assayed and evaluated in
      2.5 h. As little as 1 mg oat coleoptile tissue is sufficient for a quantitative
      IAA analysis and little or no extract purification is necessary. Using this
      assay, levels of IAA have been determined in coleoptiles of maize and oat. The
      distribution of IAA within single coleoptiles was quantitated and the production
      of IAA during the regeneration of the physiological tip in Avena coleoptiles was
      investigated. The changes in levels of IAA and other major phytohormones were
      quantitated during the growth of oat coleoptiles. 

PMID- 24275877
TI  - Control of light-induced bean leaf expansion: Role of osmotic potential, wall
      yield stress, and hydraulic conductivity.
AB  - The role of three-turgor-related cellular parameters, the osmotic potential (Psi
      s), the wall yield stress (Y) and the apparent hydraulic conductivity (L'p), in
      the initiation of ligh-induced expansion of bean (Phaseolus vulgaris L.) leaves
      has been determined. Although light causes an increase in the total solute
      content of leaf cells, the water uptake accompanying growth results in a slight
      increase in Psi s. Y is about 4 bar; and is unaffected by light. L'p, as
      calculated from growth rates and isopiestic measurements of leaf water potential,
      is only slightly greater in rapidly-growing leaves. The turgor pressure of
      growing cells is lower than that of the controls by about 35%. We conclude that
      light does not induce cell enlargement in the leaf by altering any of the above
      parameters, but does so primarily by increasing wall extensibility. 

PMID- 24275878
TI  - On the compartmentation of isopentenyl diphosphate synthesis and utilization in
      plant cells.
AB  - Purified spinach chloroplast and daffodil chromoplast preparations do not use
      mevalonate, phosphomevalonate, and diphosphomevalonate for the synthesis of
      isopentenyl diphosphate. Isopentenyl diphosphate, on the other hand, is
      incorporated into plastidal polyprenoids in large amounts. In the presence of a
      cytoplasmic supernatant, however, mevalonate and the phosphomevalonates were
      incorporated into the plastidal polyprenoids in equally large amounts, which
      demonstrates that the enzymes mevalonate kinase (EC 2.7.1.36), phosphomevalonate
      kinase (EC 2.7.4.2), and diphosphomevalonate decarboxylase (EC 4.1.1.33) are
      soluble cytoplasmic enzymes and that they apparently do not occur as isoenzymes
      within the plastids. The concept is developed that isopentenyl diphosphate is a
      central intermediate in plant polyprenoid formation which is channeled into
      several compartment for different biosynthetic pathways. 

PMID- 24275879
TI  - Influence of accumulated phosphate on culture growth and formation of cinnamoyl
      putrescines in medium-induced cell suspension cultures of Nicotiana tabacum.
AB  - The inorganic phosphate of the liquid nutrient medium was completely taken up by
      freshly inoculated cells of Nicotiana tabacum L. within the first 2 d of culture.
      Thus intracellular ortho-phosphate concentrations of approx. 0.06 M were
      accumulated, which upon growth of the cultures were diluted by cell division and
      subsequent cell growth. Cells from different stages of the growth cycle
      containing progressively decreasing levels of phosphate were transferred to a
      phosphate-free medium which normally stimulates the formation of cinnamoyl
      putrescines. The resulting accumulation of these compounds was inversely
      correlated with the intracellular phosphate level, whereas a direct linear
      relationship in the phosphate concentration was found with further growth in the
      phosphate-free medium. 

PMID- 24275881
TI  - Units, symbols, abbrevations.

PMID- 24275880
TI  - "Arabidobrassica": Chromosomal recombination and morphogenesis in asymmetric
      intergeneric hybrid cells.
AB  - A somatic hybrid cell line, cloned from an individual protoplast-fusion product
      between Arabidopsis thaliana and Brassica campestris, gave rise to formation of
      numerous plants differing drastically in morphology. Analysis of these various
      regenerants, all of which originated from one and the same heterokaryon derived
      from the fusion of two cells, shows the unspecific elimination of chromosomes of
      both parental species during the callus growth phase. Whereas the parental cells
      have so far not been sucessfully regenerated into plants, several of their
      different asymmetric hybrids are capable of morphogenesis. Furthermore,
      chromosomal analysis indicates extensive recombination. Most of the plants are
      predoinantly morphologically regular. Abnormalities are mostly limited to the
      flowers which tend to undergo phyllody. The results demonstrate that remote
      somatic hybridization may have applications although true amphidiploids may not
      be obtainable. The transfer of small units of genetic material between distantly
      related species by protoplast fusion seems to be a more realistic approach than
      the combination of complete, highly diverse genomes. 

PMID- 24275882
TI  - Hematoidin (crystallized bilirubin) crystals in an atypical meningioma.

PMID- 24275883
TI  - Extruded highly proliferative benign mucous neck cells: a peculiar histologic
      mimic of poorly cohesive gastric carcinoma.
AB  - Histologic mimics of poorly cohesive gastric carcinoma are uncommon but are
      important for pathologists to recognize. Here we report 2 cases of a novel
      histologic pattern mimicking poorly cohesive gastric carcinoma. In both cases,
      light microscopy revealed sheets of discohesive epithelial cells with prominent
      mitoses that have high proliferative activity, with a Ki67 proliferation index
      greater than 70%. One case was diagnosed as poorly cohesive carcinoma at an
      outside hospital and the other was referred in consultation as atypia of
      undetermined significance. Reexamination of the hematoxylin-eosin slides revealed
      morphologic clues that these sheets of discohesive cells represent artifactual
      extrusion of the highly proliferative neck zone from the surrounding benign
      mucosa. In contrast to poorly cohesive cancer, this artifact lacks all of the
      following diagnostic features: nuclear atypia, signet ring cell morphology, and
      intercellular stroma with infiltrating single cells between glands. Eight and 14
      months later, both patients remain cancer free. 

PMID- 24275884
TI  - Small cell tumors of the thyroid gland: a review.
AB  - The small cell group of thyroid tumors that includes lymphoma, poorly
      differentiated carcinoma, medullary carcinoma, secondary neoplasms, as well as
      tumors with uncertain histogenesis, remains as a valid diagnostic cul-de-sac due
      to its heterogeneous constitution. The existence of small cell thyroid tumors
      with EWSR1-FLI1 rearrangement together with neuroendocrine and/or carcinomatous
      differentiation raises not only differential diagnostic problems but also a very
      interesting therapeutic dilemma. This review explores the classification of small
      cell tumors of the thyroid taking into account the immunophenotype and molecular
      profile of such tumors.

PMID- 24275885
TI  - Rhabdomyoblastic differentiation in metastatic melanoma: making sense of a rare
      but complex form of mimicry.
AB  - A case of melanoma with rhabdomyoblastic differentiation is presented in the
      context of the previously reported cases. The emerging literature seeking to
      identify the molecular basis of rhabdoid and rhabdomyoblastic differentiation, as
      well as their poor prognosis, is reviewed. The combination of a diverse range of
      morphology and the potential for spontaneous primary tumor regression, despite
      metastasis, makes the accurate diagnosis of melanoma challenging. Histopathology
      review is often recommended in these cases, as is referral to a specialized
      cancer center for discussion in a multidisciplinary meeting. Improved recognition
      of this rare pattern of melanoma morphology may provide the means for omics-based
      techniques to identify novel therapeutic targets to improve the prognostic
      outlook for these patients. 

PMID- 24275886
TI  - Estimation of quizalofop ethyl residues in black gram (Vigna mungo L.) by gas
      liquid chromatography.
AB  - Quizalofop ethyl, a phenoxy propionate herbicide is used for post emergence
      control of annual and perennial grass weeds in broad-leaved crops in India. The
      experiments were designed to study the harvest time residues of quizalofop ethyl
      in black gram for two seasons. At harvest time, the residues of quizalofop ethyl
      on black gram seed, foliage and soil were found to be below the determination
      limit of 0.01 mg kg(-1) following a single application of the herbicide at 50 and
      100 g a.i. ha(-1) for both the periods. Application of the herbicide is quite
      safe from a consumer and environmental point of view.

PMID- 24275887
TI  - A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin
      superfamily gene potentially involved in sperm-egg fusion.
AB  - Fertilization is the process that leads to the formation of a diploid zygote from
      two haploid gametes. This is achieved through a complex series of cell-to-cell
      interactions between a sperm and an egg. The final event of fertilization is the
      fusion of the gametes' membranes, which allows the delivery of the sperm genetic
      material into the egg cytoplasm. In vivo studies in the laboratory mouse have led
      to the discovery of membrane proteins that are essential for the fusion process
      in both the sperm and egg. Specifically, the sperm protein Izumo1 was shown to be
      necessary for normal fertility. Izumo1-deficient spermatozoa fail to fuse with
      the egg plasma membrane. Izumo1 is a member of the Immunoglobulin Superfamily of
      proteins, which are known to be involved in cell adhesion. Here, we describe
      BART97b, a new mouse line with a recessive mutation that displays a fertilization
      block associated with a failure of sperm fusion. BART97b mutants carry a deletion
      that inactivates Spaca6, a previously uncharacterized gene expressed in testis.
      Similar to Izumo1, Spaca6 encodes an immunoglobulin-like protein. We propose that
      the Spaca6 gene product may, together with Izumo1, mediate sperm fusion by
      binding an as yet unidentified egg membrane receptor. 

PMID- 24275888
TI  - Online breath gas analysis in unrestrained mice by hs-PTR-MS.
AB  - The phenotyping of genetic mouse models for human disorders may greatly benefit
      from breath gas analysis as a noninvasive tool to identify metabolic alterations
      in mice. Phenotyping screens such as the German Mouse Clinic demand
      investigations in unrestrained mice. Therefore, we adapted a breath screen in
      which exhaled volatile organic compounds (VOCs) were online monitored by proton
      transfer reaction mass spectrometry (hs-PTR-MS). The source strength of VOCs was
      derived from the dynamics in the accumulation profile of exhaled VOCs of a single
      mouse in a respirometry chamber. A careful survey of the accumulation revealed
      alterations in the source strength due to confounders, e.g., urine and feces.
      Moreover changes in the source strength of humidity were triggered by changes in
      locomotor behavior as mice showed a typical behavioral pattern from activity to
      settling down in the course of subsequent accumulation profiles. We demonstrated
      that metabolic changes caused by a dietary intervention, e.g., after feeding a
      high-fat diet (HFD) a sample of 14 male mice, still resulted in a statistically
      significant shift in the source strength of exhaled VOCs. Applying a
      normalization which was derived from the distribution of the source strength of
      humidity and accounted for varying locomotor behaviors improved the shift. Hence,
      breath gas analysis may provide a noninvasive, fast access to monitor the
      metabolic adaptation of a mouse to alterations in energy balance due to
      overfeeding or fasting and dietary macronutrient composition as well as a high
      potential for systemic phenotyping of mouse mutants, intervention studies, and
      drug testing in mice. 

PMID- 24275889
TI  - Effect of ligand modification on the reactivity of phosphinoamide-bridged
      heterobimetallic Zr/Co complexes.
AB  - The effect of modifying the N-aryl substituent (aryl = mesityl vs. m-xylyl) of
      the phosphinoamide ligands linking Zr and Co in tris(phosphinoamide)-linked
      heterobimetallic complexes has been investigated. Treatment of the metalloligand
      ((i)Pr2PNXyl)3ZrCl (2) (Xyl = m-xylyl) with CoI2 affords the iodide-bridged
      product ICo((i)Pr2PNXyl)2(MU-I)Zr(eta(2-i)Pr2PNXyl) (3) rather than the C3
      symmetric isomer observed using the N-mesityl derivative, ICo((i)Pr2PNMes)3ZrCl.
      Upon two-electron reduction of complex 3, ligand rearrangement occurs to generate
      the three-fold symmetric reduced complex N2Co((i)Pr2PNXyl)3Zr(THF) (4).
      Comparison of 4 with the previously reported mesityl-substituted complex
      N2Co((i)Pr2PNMes)3Zr(THF) (1) reveals similar structural features but with a less
      sterically hindered Zr apical site in complex 4. An obvious electronic difference
      between these two complexes is also present based on the drastically different
      infrared N2 stretching frequencies of 1 and 4. These notable differences lend
      themselves to different reactivity in both stoichiometric and catalytic
      reactions. Alkyl halide addition to complex 4 results in homo-coupling products
      resulting from alkyl radicals rather than the alkyl-bridged or intramolecular C-H
      activation products formed upon addition of RX to 1. This difference in
      reactivity with alkyl halides renders complex 3 a less effective catalyst for the
      Kumada cross-coupling of alkyl halides with n-octylMgBr than
      ICo((i)Pr2PNMes)3ZrCl, as a greater proportion of homocoupling products are
      formed under catalytic conditions.

PMID- 24275890
TI  - Computed tomography quantification of bone density adjacent to cemented pegged
      polyethylene glenoid components in shoulder arthroplasty.
AB  - BACKGROUND: Cemented polyethylene devices are the prostheses implanted more
      frequently, but there is no agreement on the optimal glenoid component design. In
      this study, bone mineral density (BMD) adjacent to cemented all-polyethylene
      glenoid components was assessed to gain insights into the characteristics of
      glenoid bone as a potential risk factor implicated in the failure of shoulder
      arthroplasty. PATIENTS AND METHODS: Twenty-two subjects were examined at an
      average follow-up of 31 months using the Constant-Murley score (CS) and multi
      detector computed tomography. BMD was measured in 5 regions of interest (ROIs) at
      the sites where radiolucent lines are usually detected. BMD differences among the
      ROIs were tested. The relationship between BMD and a number of variables (CS
      subscores, age, gender, follow-up duration) was explored. RESULTS: There was a
      significant increase in CS scores (p<0.05). Significantly different BMD
      (p=0.0039) was found in the 5 ROIs, especially between ROIs 2 and 5 (p=0.016,
      Bonferroni's test) and between ROIs 3 and 5 (p=0.005, Bonferroni's test). BMD was
      lower in ROI 1 than ROI 3 and in ROI 2 than ROI 4, but the difference was not
      significant. DISCUSSION: The heterogeneous BMD distribution may be related to:
      (1) an interindividual variability in glenoid BMD; (2) the fixation technique; or
      (3) the different bone response to eccentric loading of the prosthetic head on
      the glenoid component. CONCLUSIONS: BMD analysis may contribute to extent our
      knowledge on glenoid component loosening and encourage further techniques of
      glenoid fixation.

PMID- 24275892
TI  - Initiative to test a multidisciplinary model with advanced practice nurses to
      reduce avoidable hospitalizations among nursing facility residents.

PMID- 24275891
TI  - Percutaneous autologous concentrated bone marrow grafting in the treatment for
      nonunion.
AB  - The purpose of this study was to evaluate the clinical and radiographic treatment
      effects of percutaneous autologous concentrated bone marrow grafting in nonunion
      cases and to evaluate the effectiveness of this grafting procedure. We enrolled
      17 cases those had atrophic changes due to continuous nonunion for over 9 months
      after injury and had undergone low-intensity pulsed ultrasound treatment for more
      than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5
      cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous
      autologous concentrated bone marrow grafting and continued low-intensity pulsed
      ultrasound stimulation treatment after grafting. Patients were evaluated using
      the visual analogue scale for pain at immediately before the procedure, 3, 6, and
      12 months after grafting. Plain radiographs of the affected site were taken and
      evaluated about the healing of the nonunion site at each clinical evaluation. As
      quantitative assessment, CT scans were undertaken before the procedure and 6
      months after grafting. The visual analogue scale pain score was reduced
      consistently after grafting in all patients. About the healing at the nonunion
      site, 11 and 13 cases of bone union were observed at 6 and 12 months after
      grafting. The mean volume of callus formation based on CT images was 4,147 (262
      27,392) mm3 total between grafting and 6 months. Percutaneous autologous
      concentrated bone marrow grafting is an effective procedure for the treatment of
      patients with nonunion.

PMID- 24275893
TI  - Mesenchymal stromal cells for organ transplantation: different sources and unique
      characteristics?
AB  - PURPOSE OF THE REVIEW: In this review, recent findings on the effects of tissue
      and donor origin, culturing conditions and preconditioning regimens on the
      therapeutic effect of mesenchymal stem cells (MSC) in organ transplantation are
      discussed and the importance of understanding the characteristics of MSC for
      developing efficient therapy is stressed. RECENT FINDINGS: MSC research in organ
      transplantation is currently moving from safety-feasibility studies to efficacy
      studies and finding the optimal MSC for therapy is therefore highly relevant.
      Although sharing basic properties, there are subtle differences between MSC from
      different tissue sources that may affect their efficacy. Furthermore, the use of
      MSC from diseased organ recipients, donor or third party may affect their
      therapeutic effect. The importance of these differences in MSC properties may
      however be overshadowed by the impact of culture conditions on MSC. Culture
      conditions dramatically change the characteristics of MSC, and this situation can
      be exploited by exposing MSC to preconditioning treatment to bring about the
      desired properties in MSC. As MSC appear to be short-lived after infusion, the
      specific characteristics of MSC are mostly relevant for short-term interactions
      between MSC and host cells, which will subsequently take over the effects of MSC.
      The multiple effects of MSC are by no means unique, but the full spectrum of the
      effects in combination with their easy isolation and expansion make MSC a
      suitable cell type for therapy. SUMMARY: Tissue source, donor source and culture
      conditions affect the phenotypical and functional properties of MSC. The efficacy
      of MSC therapy will therefore depend on the source and manipulation of MSC.

PMID- 24275894
TI  - Mesenchymal stromal cells to prevent fibrosis in kidney transplantation.
AB  - PURPOSE OF REVIEW: Kidney transplantation has improved the life expectancy and
      quality of life for patients with end-stage renal failure. However, despite the
      impressive improvements in short-term outcome parameters because of better and
      more potent immunosuppressive drugs, the long-term survival of renal allografts
      has changed little over the last decades. Sustained inflammation in the areas of
      interstitial fibrosis and tubular atrophy (IFTA) is a strong predictor of
      allograft failure. Mesenchymal stromal cells (MSCs) have potent anti-inflammatory
      and reparative properties, and could thus play a role in controlling these
      processes. RECENT FINDINGS: Local resident MSCs and exogenous MSCs have been
      implicated in the repair of the injured kidney, mostly by their paracrine
      functions. In the experimental models and clinical trials, first results with
      MSCs for the treatment of inflammation and IFTA suggest beneficial effects.
      SUMMARY: Endogenously and exogenously administered MSCs might enhance the
      intrinsic reparative capabilities of the kidney in transplant recipients and
      maybe developed as a tool to control both inflammation and fibrosis.

PMID- 24275895
TI  - Neuropsychological outcomes after psychosocial intervention for depression in
      Parkinson's disease.
AB  - The authors describe neuropsychological outcomes in people with Parkinson's
      disease (PD) after their participation in an NIH-sponsored, randomized,
      controlled trial of cognitive-behavioral treatment for depression. Improvements
      in mood were associated with modest gains in verbal memory and executive
      functioning over the 10-week treatment period and accounted for greater variance
      in neuropsychological outcomes at the end of treatment than other known
      correlates of cognitive functioning in PD, such as disease severity, age, and
      education. Baseline working memory and executive skills were also associated with
      depression improvement over time. 

PMID- 24275897
TI  - A to-do list for the next US surgeon general.

PMID- 24275896
TI  - Probing the metal specificity mechanism of superoxide dismutase from human
      pathogen Clostridium difficile.
AB  - The molecular mechanism of the metal specificity to superoxide dismutase from
      human pathogen C. difficile (SODcd) was investigated by X-ray crystallography,
      spectroscopy, SOD activity assay, electrochemistry, and DFT calculations, and the
      results indicate that the cognate metal characters tuned by the metal micro
      environment dominate the metal specificity of the SODcd. 

PMID- 24275898
TI  - Multiple-timescale relaxation dynamics in CsGd(MoO4)2--a dipolar magnet with a
      highly anisotropic layered crystal structure.
AB  - The dynamic properties of the dipolar magnet CsGd(MoO4)2 have been studied. The
      frequency and temperature dependence of the AC susceptibility investigated in the
      paramagnetic region above 2 K revealed the co-existence of magnetic field induced
      slow and fast relaxation channels with a timescale differing by three orders of
      magnitude. The slow relaxation is determined by the properties of the first
      coordination sphere of the Gd(3+) ion and has the character of a two-phonon
      Orbach process. The fast relaxation is potentially attributed to a two-phonon
      Raman process realized via a localized phonon mode associated with the layered
      crystal structure. The temperature dependence of the phonon mean free path in
      zero magnetic field indicates significant phonon scattering below 1 K resulting
      from the combined effect of magnetic correlations and the scattering of dominant
      phonons with energies corresponding to the crystal-field levels. 

PMID- 24275899
TI  - An infant with an ectopic torsed testis in the abdominal wall.
AB  - We report a unique case of an infant with testicular torsion in the anterior
      abdominal wall. In the work-up of acute abdominal pain in a male infant with
      nonpalpable testes, a careful search for the testes using ultrasound can often
      identify undescended or ectopic testes. Testicular torsion should remain an
      important consideration as a potential cause of abdominal pain in this selected
      group of individuals. 

PMID- 24275902
TI  - Old wine in new bottles: should we publish old data?

PMID- 24275900
TI  - Impact of the humidification device on intubation rate during noninvasive
      ventilation with ICU ventilators: results of a multicenter randomized controlled
      trial.
AB  - PURPOSE: The use of heat and moisture exchangers (HME) during noninvasive
      ventilation (NIV) can increase the work of breathing, decrease alveolar
      ventilation, and deliver less humidity in comparison with heated humidifiers
      (HH). We tested the hypothesis that the use of HH during NIV with ICU ventilators
      for patients with acute respiratory failure would decrease the rate of intubation
      (primary endpoint) as compared with HME. METHODS: We conducted a multicenter
      randomized controlled study in 15 centers. After stratification by center and
      type of respiratory failure (hypoxemic or hypercapnic), eligible patients were
      randomized to receive NIV with HH or HME. RESULTS: Of the 247 patients included,
      128 patients were allocated to the HME group and 119 to the HH group. Patients
      were comparable at baseline. The intubation rate was not significantly different:
      29.7% in the HME group and 36.9% in the HH group (p = 0.28). PaCO2 did not
      significantly differ between the two arms, even in the subgroup of hypercapnic
      patients. No significant difference was observed for NIV duration, ICU and
      hospital LOS, or ICU mortality (HME 14.1 vs. HH 21.5%, p = 0.18). CONCLUSIONS: In
      this study, the short-term physiological benefits of HH in comparison with HME
      during NIV with ICU ventilators were not observed, and no difference in
      intubation rate was found. The physiologic effects may have been obscured by
      leaks or other important factors in the clinical settings. This study does not
      support the recent recommendation favoring the use of HH during NIV with ICU
      ventilators.

PMID- 24275904
TI  - Complex spectral evolution in a BCS superconductor, ZrB12.
AB  - We investigate the electronic structure of a complex conventional superconductor,
      ZrB12 employing high resolution photoemission spectroscopy and ab initio band
      structure calculations. The experimental valence band spectra could be described
      reasonably well within the local density approximation. Energy bands close to the
      Fermi level possess t2g symmetry and the Fermi level is found to be in the
      proximity of quantum fluctuation regime. The spectral lineshape in the high
      resolution spectra is complex exhibiting signature of a deviation from Fermi
      liquid behavior. A dip at the Fermi level emerges above the superconducting
      transition temperature that gradually grows with the decrease in temperature. The
      spectral simulation of the dip and spectral lineshape based on a phenomenological
      self energy suggests finite electron pair lifetime and a pseudogap above the
      superconducting transition temperature. 

PMID- 24275901
TI  - Palliative care in the ICU: relief of pain, dyspnea, and thirst--a report from
      the IPAL-ICU Advisory Board.
AB  - PURPOSE: Pain, dyspnea, and thirst are three of the most prevalent, intense, and
      distressing symptoms of intensive care unit (ICU) patients. In this report, the
      interdisciplinary Advisory Board of the Improving Palliative Care in the ICU
      (IPAL-ICU) Project brings together expertise in both critical care and palliative
      care along with current information to address challenges in assessment and
      management. METHODS: We conducted a comprehensive review of literature focusing
      on intensive care and palliative care research related to palliation of pain,
      dyspnea, and thirst. RESULTS: Evidence-based methods to assess pain are the
      enlarged 0-10 Numeric Rating Scale (NRS) for ICU patients able to self-report and
      the Critical Care Pain Observation Tool or Behavior Pain Scale for patients who
      cannot report symptoms verbally or non-verbally. The Respiratory Distress
      Observation Scale is the only known behavioral scale for assessment of dyspnea,
      and thirst is evaluated by patient self-report using an 0-10 NRS. Opioids remain
      the mainstay for pain management, and all available intravenous opioids, when
      titrated to similar pain intensity end points, are equally effective. Dyspnea is
      treated (with or without invasive or noninvasive mechanical ventilation) by
      optimizing the underlying etiological condition, patient positioning and,
      sometimes, supplemental oxygen. Several oral interventions are recommended to
      alleviate thirst. Systematized improvement efforts addressing symptom management
      and assessment can be implemented in ICUs. CONCLUSIONS: Relief of symptom
      distress is a key component of critical care for all ICU patients, regardless of
      condition or prognosis. Evidence-based approaches for assessment and treatment
      together with well-designed work systems can help ensure comfort and related
      favorable outcomes for the critically ill.

PMID- 24275905
TI  - Electrocardiographic J waves are associated with right ventricular morphology and
      function: evaluation by cardiac magnetic resonance imaging.
AB  - We assessed the relationship between J waves and the ventricular morphology and
      function using cardiac magnetic resonance imaging (MRI). The 12-lead
      electrocardiograms (ECGs) of 105 consecutive patients who underwent cardiac MRI
      were reviewed, and those with signs of arrhythmogenic right ventricular
      cardiomyopathy, complete left bundle branch block, complete right bundle branch
      block, or chronic atrial fibrillation, where the J wave is difficult to
      distinguish, were excluded. The ECGs of the remaining 68 patients were analyzed
      for the presence of J waves. Ventricular morphologic abnormalities were
      identified on MRI, based on the largest short-axis diameter in the right and left
      ventricles (d-RVmax/d-LVmax), the area (a-RVmax/a-LVmax), and the ratio RV/LVmax.
      The percentage contraction of the RV (PC-RV) was used as a measure of ventricular
      function. Thirty-two patients (47.0 %) had J waves defined as QRS-ST junction
      elevation >0.1 mV from baseline in the inferior/lateral leads (J group; 56 +/- 15
      years; 19 males). Thirty-six patients (53.0 %) did not present J waves (NJ group;
      58 +/- 15 years; 27 males). The d-RVmax and a-RVmax in the J group were larger
      than those in the NJ group (41 +/- 5.2 vs 36 +/- 6.6 mm, P = 0.002 and 14 +/- 2.9
      vs 12 +/- 3.4 cm(2), P = 0.022, respectively). The RV/LVmax ratio in the J group
      was larger than that in the NJ group (0.83 +/- 0.15 vs 0.68 +/- 0.15, P < 0.001).
      The PC-RV in the J group was smaller than that in the NJ group (0.28 +/- 0.14 vs
      0.36 +/- 0.15, P = 0.013). J-wave amplitude was correlated positively with d
      RVmax (P = 0.010) and negatively with PC-RV (P = 0.005). These results suggested
      that J waves are associated with right ventricular morphologic and functional
      abnormalities.

PMID- 24275906
TI  - Descending aorta-external iliac artery bypass for middle aortic syndrome.
AB  - We encountered a surgical case of middle aortic syndrome (MAS) in a 56-year-old
      man who had resistant hypertension. Computed tomography showed severe stenosis of
      the abdominal aorta from below the superior mesenteric artery to above the
      inferior mesenteric artery. Although bilateral renal artery stenosis was
      confirmed, renal function was within normal limits. A 10-mm vascular prosthetic
      graft was used to perform a descending aorta to left external iliac artery
      bypass. His hypertension was well controlled without medication. This extra
      anatomic bypass may be a simple and useful approach for treating MAS if it is not
      necessary to reconstruct the renal artery or visceral artery. 

PMID- 24275907
TI  - Rapidly progressive symptom development of pulmonary arterial hypertension: a
      case report of Trousseau syndrome.
AB  - Trousseau syndrome is most commonly defined as a hypercoagulability syndrome
      associated with mucin-producing adenocarcinoma. We report here a rare case of
      Trousseau syndrome presenting as pulmonary arterial hypertension. The patient
      complained of cough and increasing exertional dyspnea. Rapidly progressive
      symptom development of pulmonary arterial hypertension accompanied by right heart
      failure was observed, and the patient died on hospital day 2. An autopsy revealed
      Krukenberg tumors on both ovaries and a signet-ring cell gastric carcinoma. In
      the lungs there was tumor embolism with signet-ring cells to some extent, but the
      peripheral pulmonary arteries were occupied primarily by pulmonary embolism with
      platelets, fibroblasts, and fibrotic organized thrombi. 

PMID- 24275908
TI  - Prevalence and the long-term prognosis of functional mitral regurgitation in
      Japanese patients with symptomatic heart failure.
AB  - Functional mitral regurgitation (FMR) is a common and critical condition in
      patients with heart failure (HF); however, the prevalence and clinical outcome of
      FMR in Japanese real-world clinical practice remain unclear. Within a single
      hospital-based cohort in the Shinken Database 2004-2011, which comprised all new
      patients (n = 17,517) who visited the Cardiovascular Institute, we followed
      symptomatic HF patients. A total of 1,701 patients were included: 104 FMR
      patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had
      none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia,
      but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York
      Heart Association functional class III/IV. FMR patients had higher levels of
      brain natriuretic peptide and lower left ventricular function. Use of
      cardiovascular drugs was more common among FMR patients. Kaplan-Meier curves
      revealed that the incidences of all-cause death, cardiovascular death, and
      admission for HF were significantly higher in FMR patients. The adjusted Cox
      regression analysis showed that significant FMR was associated with higher
      incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval
      (CI) 1.266-3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157
      4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133-2.920; P =
      0.013). FMR was common in Japanese symptomatic HF patients and was associated
      with adverse long-term outcomes. Establishing optimal therapeutic strategies for
      FMR is warranted. 

PMID- 24275909
TI  - A randomized controlled trial of psychoanalytic psychotherapy or cognitive
      behavioral therapy for bulimia nervosa.
AB  - OBJECTIVE: The authors compared psychoanalytic psychotherapy and cognitive
      behavioral therapy (CBT) in the treatment of bulimia nervosa. METHOD: A
      randomized controlled trial was conducted in which 70 patients with bulimia
      nervosa received either 2 years of weekly psychoanalytic psychotherapy or 20
      sessions of CBT over 5 months. The main outcome measure was the Eating Disorder
      Examination interview, which was administered blind to treatment condition at
      baseline, after 5 months, and after 2 years. The primary outcome analyses were
      conducted using logistic regression analysis. RESULTS: Both treatments resulted
      in improvement, but a marked difference was observed between CBT and
      psychoanalytic psychotherapy. After 5 months, 42% of patients in CBT (N=36) and
      6% of patients in psychoanalytic psychotherapy (N=34) had stopped binge eating
      and purging (odds ratio=13.40, 95% confidence interval [CI]=2.45-73.42; p<0.01).
      At 2 years, 44% in the CBT group and 15% in the psychoanalytic psychotherapy
      group had stopped binge eating and purging (odds ratio=4.34, 95% CI=1.33-14.21;
      p=0.02). By the end of both treatments, substantial improvements in eating
      disorder features and general psychopathology were observed, but in general these
      changes took place more rapidly in CBT. CONCLUSIONS: Despite the marked disparity
      in the number of treatment sessions and the duration of treatment, CBT was more
      effective in relieving binging and purging than psychoanalytic psychotherapy and
      was generally faster in alleviating eating disorder features and general
      psychopathology. The findings indicate the need to develop and test a more
      structured and symptom-focused version of psychoanalytic psychotherapy for
      bulimia nervosa.

PMID- 24275910
TI  - The genetic relationship between the tomato mutants, flacca and lateral
      suppressor, with reference to abscisic acid accumulation.
AB  - Two tomato mutants, Lycopersicon esculentum flacca and lateral suppressor, are
      assigned to map position 59 of chromosome 7. The tight linkage between these two
      gene loci was detected as a result of attempts to establish whether they would
      exhibit phenotypic interaction. The possibility that both mutants result in
      abnormalities of abscisic acid (ABA) accumulation is considered. ABA analysis
      supports the suggestion that plants homozygous for flacca have a substantially
      lower concentration but indicates that lateral suppressor homozygotes do not
      differ from normal in ABA content. An attempt is made to reconcile the results
      with those of Tucker (1976, New. Phytol. 77, 561-568) by suggesting that lateral
      suppressor plants may accumulate high levels of an ABA metabolite which is
      indistinguishable from ABA using the Commelina epidermal strip bioassay. 

PMID- 24275911
TI  - Glycinebetaine biosynthesis and its control in detached secondary leaves of
      spinach.
AB  - In secondary leaves from spinach plants pretreated in vermiculite for 24 h with
      300 mM NaCl, glycinebetaine accumulated at a rate of circa 0.16 MUmol 100 MUg(-1)
      Chl d(-1) (2 MUmol g(-1) FW d(-1)), about three times the rate of control plants.
      The soluble carbohydrate and free amino acid contents did not increase
      significantly following salinisation until after 4 d when the relative growth
      rate also decreased. Leaf proline levels remained very low throughout the
      experimental period. K(+) on a tissue water basis remained constant at 200 mM
      while Cl(-) and Na(+) levels increased linearly to reach 175 and 100 mM
      respectively after 5 d of saline treatment. The osmotic pressure of leaf tissue
      also increased from 300 to 500 mosmol kg(-1). These experimental conditions were
      considered suitable to study glycinebetaine biosynthesis and its induction by
      salinity in the absence of marked growth inhibition or metabolic disturbance.
      Radioactive labelled [(14)C]serine, ethanolamine and choline (all 1 MUmol, 13.3
      MBq in 10 MUl) were fed to detached secondary leaves via the petiole 24 h after
      the exposure of plants to salt. The rate of isotope incorporation into water
      soluble products, lipids and residue was measured over a further 24 h. The major
      metabolic fate of exogenous [(14)C]choline and [(14)C]ethanolamine was
      incorporation into glycinebetaine while less (14)C-label was found in
      phosphatidyl choline and phosphatidyl ethanolamine. Incorporation rates were
      identical in control and salinised leaves and were adequate to account for
      observed values of glycinebetaine accumulation previously reported in spinach. In
      contrast the labelling of glycinebetaine from [(14)C]serine was twice as great in
      salinated plants as in the controls. These results, together with short term
      labelling experiment with [(14)C]ethanolamine using leaf slices, were consistent
      with the formation of glycinebetaine via serine, ethanolamine and its methylated
      derivatives to choline with some control being exerted at the serine level.
      However a flux through the phosphorylated intermediates is not excluded.From a
      consideration of these results and the published data on barley subjected to
      water stress (Hanson and Scott, 1980 Plant Physiol. 66, 342-348) there appear to
      be significant differences in the biosynthetic pathways in spinach and barley. 

PMID- 24275912
TI  - Expression of genes for plastid membrane proteins in barley under intermittent
      light conditions.
AB  - Barley plants grown under intermittent light show a plastid membrane composition
      intermediate between those of etioplasts and chloroplasts. In particular
      protochlorophyll reductase disappears from the membranes whereas the 32000
      protein, coded for by chloroplast DNA, becomes integrated into the membranes. The
      light-harvesting chlorophyll a/b protein does not accumulate within the membranes
      even after 11 d of development, while the corresponding mRNA can already be
      observed after 4 d and is translated under in vivo conditions. 

PMID- 24275913
TI  - Stress-related levels of abscisic acid in guard cell protoplasts of Vicia faba L.
AB  - Levels of abscisis acid (ABA) were determined in isolated guard cell (GCP) and
      mesophyll cell (MCP) protoplasts of Vicia faba L. in relation to water stress.
      Incubation of GCP and MCP in 0.4 M or 0.8 M mannitol resulted in an average
      increase in the level of free abscisic acid (ABA) in the cells of 34% (GCP) and
      38% (MCP) within 15-60 min. It is concluded that guard cell protoplasts form ABA
      in response to osmotic stress. 

PMID- 24275914
TI  - Protoplasts isolated from aleurone layers of wild oat (Avena fatua L.) exhibit
      the classic response to gibberellic acid.
AB  - Viable, long-lived, gibberellic acid (GA3)-responsive protoplasts have, for the
      first time, been isolated from aleurone layers of mature wild oat (Avena fatua
      L.) grain. More than 90% of the cells of aleurone layers are recovered as
      protoplasts, and these respond to treatment with GA3 in essentially the same
      manner as the tissue from which they were derived. Protoplasts become vacuolate
      during incubation in vitro and, although not dependent upon GA3, vacuolation is
      markedly stimulated by the hormone. Amylase and ribonuclease (RNase) are produced
      and secreted only in the presence of GA3 and only after lag periods of 3 d and 4
      d respectively. The amounts of amylase produced and secreted are proportional to
      GA3 concentrations as low as 1.61.10(-13) M. With increasing concentrations of
      mannitol in the culture medium both vacuolation and the GA3-induced production
      and secretion of enzymes are inhibited progressively, the latter being precluded
      by 0.6 M to 0.7 M mannitol. 

PMID- 24275915
TI  - The influence of metal cations and pH on the heat sensitivity of photosynthetic
      oxygen evolution and chlorophyll fluorescence in spinach chloroplasts.
AB  - The heat-sensitivity of photosynthetic oxygen evolution of thylakoids isolated
      from spinach increases by increasing the pH above neutral value. The temperature
      for inactivation (transition temperature) is lowered from about 45 degrees  C (pH
      6.0-7.4) to 33 degrees C (pH 8.5). Similar results are obtained with intact
      chloroplasts. At pH 7.0 the transition temperature of washed thylakoids decreases
      by lowering the salt concentration below 20 mM with monovalent cations (Li(+),
      Na(+), K(+)) and below 3-4 mM with divalent cations (Mg(2+), Ca(2+), Sr(2+)).
      Illumination decreases the heat-sensitivity of oxygen evolution in intact
      chloroplasts, but even increases the heat-sensitivity in uncoupled chloroplasts.
      In intact chloroplasts the transition temperature of the heat-induced rise in
      chlorophyll fluorescence yield (Fo; see Schreiber and Armond 1978) decreases from
      44 degrees  C to 38 degrees  C when the pH of the suspending medium is increased
      from 6.5 to 8.5. At 20 degrees  C, Fo is almost insensitive to pH (6.0-8.5). At
      40 degrees  C, however, Fo is constant between 6.0 and 7.0, but strongly
      increases by increasing the pH above neutral value. The results are discussed in
      terms of a close relation between electrostatic forces at the thylakoid membrane
      and thermal sensitivity of photosynthetic apparatus. It is suggested that the
      heat-sensitivity of the photosystem II complex partially depends on the
      ionization state of fixed groups having alkaline pK. The "packed volume" of
      thylakoids suspended in a low salt medium increases when the temperature is
      increased above 30 degrees  C (pH 7.0) and above 20 degrees  C (pH 8.0),
      respectively. This result suggests a heat-induced increase in surface charge
      density of the thylakoid membrane. 

PMID- 24275916
TI  - A study of the subcellular localisation of an ethylene binding site in developing
      cotyledons of Phaseolus vulgaris L. by high resolution autoradiography.
AB  - Use was made of light microscopy and high resolution electron microscope
      autoradiography to determine the subcellular localisation of a binding site with
      a high affinity and specificity for ethylene in developing cotyledons of
      Phaseolus vulgaris L. The results indicate that the binding site is located on
      the endoplasmic reticulum and protein body membranes, confirming previous studies
      using cellular fractionation and marker enzymes. 

PMID- 24275917
TI  - Isolation of RNA polymerases from the water mold Achlya.
AB  - The DNA-dependent RNA polymerases I, II, and III (ribonucleosidetriphosphate: RNA
      nucleotidyl-transferase, EC 2.7.7.6) from Achlya ambisexualis E87 (male), have
      been isolated. The highly purified RNA polymerase I was found to be composed of
      polypeptides with the following molecular weights (.10(-4)): 18.5, 14, 11.8, 7.3,
      6.1, 4.9, 4.4, 2.8. RNA polymerase II showed a 400-fold higher resistance against
      alpha-amanitin than mammalian or higher plant RNA polymerase II. 

PMID- 24275918
TI  - The synthesis of palmitoylcarnitine by etio-chloroplasts of greening barley
      leaves.
AB  - CoASH, Mg(2+), ATP and (-)-carnitine were found to be essential for the
      production of palmitoylcarnitine from palmitate by purified barley etio
      chloroplasts. It was concluded that long-chain acyl CoA synthetase (palmitoyl CoA
      synthetase, EC 6.2.1.3) and carnitine long-chain acyl-transferase (carnitine
      palmitoyltransferase, EC 2.3.1.21) activity were present in the etio
      chloroplasts. It is suggested that the long-chain acylcarnitine formed may move
      more easily through membrane barriers than the long-chain acyl CoA compound. Also
      or alternatively this enzyme may spare CoA by transferring long-chain acyl groups
      from long-chain acyl CoA to carnitine. 

PMID- 24275919
TI  - The site of carotenogenic enzymes in chromoplasts from Narcissus pseudonarcissus
      L.
AB  - The membranes from the chromoplasts of Narcissus pseudonarcissus L. which are
      derived from the inner envelope membrane are the site of beta-carotene synthesis
      from [1-(14)C]isopentenyl diphosphate. The enzymes involved are partly peripheral
      membrane proteins (prenyltransferase, phytoene synthase) and partly integral
      membrane proteins (cis-trans isomerase, dehydrogenase(s), cyclase(s)). Metabolic
      channeling is suggested. 

PMID- 24275920
TI  - Photosynthetic activity of isolated chloroplasts from Euglena gracilis.
AB  - Functional chloroplasts from photoheterotrophic Euglena gracilis can be isolated
      in isoosmotic gradients of 10-80% Percoll. The chloroplasts display rates of CO2
      dependent O2 evolution and CO2 fixation of 30-50 MUmol mg(-1) chlorophyll h(-1)
      or 25-35% of the net O2 evolution by the whole cells and appear to be strikingly
      different from spinach chloroplasts in several respects: 1. tolerance to high
      concentration of orthophosphate in the assay medium; 2. inability to support
      oxaloacetate-dependent O2 evolution; 3. ability to support only low to moderate
      rates of 3-phosphoglycerate-dependent O2 evolution; 4. an apparent absence of a
      phosphate translocator in the terms described by Heldt and Rapley ([1970] FEBS
      Lett. 10, 143-148). 

PMID- 24275921
TI  - Fine structure of isolated and non-isolated potato tuber periderm.
AB  - Cell walls of the periderm of native potato tuber (Solanum tuberosum L. cv.
      Primura) consist of a primary wall, a suberized secondary wall and a tertiary
      wall. With a mixture of pectinase and cellulase intact periderm membranes can be
      isolated. Isolation does not affect fine structure. It is suggested that the
      lignin in the middle lamellae and primary walls prevents the enzymes from
      digesting pectinaceous materials and cellulose. In specimens fixed with OsO4, the
      suberized walls appear as alternating electrondense and electron-lucent lamellae.
      This lamellar architecture is not altered by extraction with chloroform.
      Therefore, the current view that the electronlucent lamellae consist of soluble
      lipids (waxes) can no longer be maintained. It is argued that the lamellation is
      a property of the suberin itself, and the suberized wall consists of alternating
      layers of suberins differing in polarity. A hypothesis of suberin assembly from
      sub-units is advanced and the subunits are shown for the first time. 

PMID- 24275922
TI  - Phytochrome control of plastid mRNA in mustard (Sinapis alba L.).
AB  - The steady-state levels of plastid RNA sequences in dark-grown and light-grown
      mustard (Sinapis alba L.) seedlings have been compared. Total cellular RNAs were
      labeled in vitro with (32)P and hybridized to separated restriction fragments of
      plastid DNA. Cloned DNA fragments which encode the large subunit (LS) of ribulose
      1,5-bisphosphate carboxylase [3-phospho-D-glycerate carboxylase (dimerizing), EC
      4.1.1.39] and a 35,000 plastid polypeptide were used as probes to assess the
      levels of these two plastid mRNAs. The 1.22-kilobase-pair mRNA for the 35,000
      polypeptide is almost undetectable in dark-grown seedlings, but is a major
      plastid mRNA in light-grown seedlings. The hybridization analysis of RNA from
      seedlings which were irradiated with red and far-red light indicates that the
      level of this mRNA, but not of LS mRNA, is controlled by phytochrome. 

PMID- 24275923
TI  - Characterization of maltose biosynthesis from alpha-D-glucose-1-phosphate in
      Spinacia oleracea. L.
AB  - The de novo synthesis of maltose in spinach (Spinacia oleracea L.) was shown to
      be catalyzed by a maltose synthase, which converts two molecules of alpha-D
      glucose-1-phosphate (alpha-G1P) (Km 1.5 mmol l(-1)) to maltose and 2
      orthophosphate (Pi). This enzyme was purified 203-fold by fractionated ammonium
      sulfate precipitation and by column chromatography on Sepharose 6B. The addition
      of alpha-G1P (15 mmol l(-1)) to the isolation buffer is required to stabilize the
      enzyme activity during the extraction and purification procedure. Molecular
      weight determination by gel filtration yielded a value of 95,000. delta
      Gluconolactone, ATP and Pi are competitive inhibitors toward the substrate alpha
      G1P. The maltose synthase catalyzes an exchange of the phosphate group of alpha
      G1P with [(32)P] orthophosphate; this transfer reaction suggests that the
      synthesis of maltose occurs via a glucose-enzyme in a double displacement
      reaction. The physiological role of this enzyme as a "starch initiator system" is
      discussed. 

PMID- 24275924
TI  - Stimulation of sugar loading into sieve elements of willow by potassium and
      sodium salts.
AB  - Potassium as the chloride, nitrate or sulphate or sodium as the chloride, were
      applied at a concentration of 50 mM either to the xylem of stem segments or to
      the cambial surface of bark strips of willow. Potassium chloride increased the
      concentration of sucrose in sieve tube exudate collected via severed aphid
      stylets, without significantly affecting the volume flow rate, or the
      concentration of potassium in the exudate. The increase in the sucrose level in
      the sieve tube sap was shown to be due to a stimulation of loading, rather than
      to an enhancement of longitudinal transport. Potassium nitrate and sulphate or
      sodium chloride, were not as effective as potassium chloride in stimulating the
      loading of sucrose. It is suggested that uptake of the cation into cells
      supplying sugars to the sieve tube is linked to the rate of release of sugars by
      the supplying cells. 

PMID- 24275925
TI  - Systems biology approach for subtyping asthma; where do we stand now?
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the present systems
      biology approach to asthma and how it is helping to define asthma subtypes.
      Although the general concept of systems biology will be discussed, the article
      will focus on recent developments in the field related to asthma. RECENT
      FINDINGS: The most recent work in systems biology and asthma has occurred in the
      area of genomics (e.g., pharmacogenomics and gene-environment interactions),
      protein interaction networks [e.g., interleukin (IL)-33/IL-1 receptor-like 1
      signaling], cluster analysis of asthma patients (e.g., application of severe
      asthma research program clusters to a general urban asthma population), and
      multiscale approaches to asthma encompassing data from the molecule to whole
      organ (e.g., modeling of airways hyperresponsiveness). SUMMARY: The results of
      recent work in this area have led to new insight into gene-cytokine and protein
      protein networks involved in asthma, a better determination of key clinical
      factors associated with asthma subtypes, and the beginning of sophisticated
      multiscale approaches to modeling, understanding and predicting the behavior of
      the asthmatic lung.

PMID- 24275926
TI  - Revisiting the role of exhaled nitric oxide in asthma.
AB  - PURPOSE OF REVIEW: This review focuses on the most recent studies investigating
      fractional nitric oxide concentration in exhaled breath (FeNO) as a useful
      biomarker for identifying specific phenotypes in asthma and as a tool for asthma
      diagnosis, monitoring and clinical decision-making. RECENT FINDINGS: On the basis
      of the current literature, it has been highlighted that FeNO is a clinically
      relevant marker in various clinical aspects of asthma: FeNO is a predictor for
      developing asthma in persistent rhinitis or in infants with respiratory symptoms;
      FeNO contributes to identification of asthma phenotypes in both children and
      adults, also in relation to severity; FeNO is useful in monitoring the
      effectiveness of inhaled corticosteroids (including compliance) and biologic
      treatments like omalizumab; FeNO, in conjunction with symptom registration and
      lung function measurements, contributes to asthma diagnosis and optimizes asthma
      management. SUMMARY: FeNO provides further information in distinguishing
      different phenotypes in asthma, allowing a much more appropriate control of the
      disease, especially in patients with difficult/severe asthma. In the future, it
      would be interesting to shed light on the hidden biological mechanisms
      responsible for low or normal FeNO values in symptomatic asthmatic patients.

PMID- 24275927
TI  - Monoclonal antibodies for the treatment of refractory asthma.
AB  - PURPOSE OF REVIEW: A small proportion of patients with asthma have severe disease
      characterized by persistent airflow obstruction, airway hyperresponsiveness and
      eosinophilic airway inflammation. This review focuses on the clinical efficacy of
      inhibiting T helper 2-cytokine-mediated inflammatory responses using monoclonal
      antibodies directed against immunoglobulin E (IgE), interleukin (IL)-5, and IL
      4/IL-13 in patients with severe refractory asthma. RECENT FINDINGS: The
      heterogeneity of airway inflammation in severe asthma has led to the recognition
      of multiple pathophysiologically distinct severe asthma endotypes. Biomarkers are
      being developed and evaluated to identify these endotypes and to guide the use of
      specific biologics in the appropriate patients who remain uncontrolled on high
      doses of inhaled corticosteroids and long-acting bronchodilators or oral
      corticosteroids. Examples include the efficacy of omalizumab in patients with
      severe refractory atopic asthma characterized by raised serum total IgE,
      mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic
      exacerbations characterized by blood and sputum eosinophilia despite high doses
      of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab
      that target the IL-4/IL-13 signalling pathways in patients with eosinophilic
      asthma or raised serum periostin. SUMMARY: In severe refractory asthma, both an
      understanding of the underlying pathophysiologic mechanisms driving airway
      inflammation and the identification of appropriate biomarkers in individual
      patients are critical in guiding the use of biologics and monoclonal antibodies
      that target the specific pathological processes.

PMID- 24275928
TI  - Bronchoprovocation tests in asthma: direct versus indirect challenges.
AB  - PURPOSE OF REVIEW: This review describes different bronchoprovocation tests and
      their merits in diagnosing asthma. RECENT FINDINGS: A new indirect challenge test
      using dry powder mannitol has been made available and has been systematically
      validated and tested in different populations. SUMMARY: Airway
      hyperresponsiveness (AHR) is a characteristic feature of asthma, and its
      measurement using direct inhalation challenges, particularly with inhaled
      methacholine or histamine, or indirect challenges using stimuli such as exercise,
      dry air hyperpnea, distilled water, hypertonic saline and mannitol, and the
      pharmacological agent adenosine monophosphate is important in establishing a
      correct diagnosis. Direct challenge tests are sensitive and have a high negative
      predictive value to exclude asthma. This is particularly true in excluding asthma
      as a diagnosis in patients with symptoms that suggest asthma, but are caused by
      another condition. Indirect AHR correlates better with eosinophilic airway
      inflammation. Therefore, indirect challenge tests are seen as more specific. A
      newer indirect challenge test that uses a kit containing prepacked capsules of
      dry powder mannitol in different doses is safe and efficient to use. Indirect
      challenge tests are superior to direct challenge tests to confirm the presence of
      asthma.

PMID- 24275929
TI  - Neurocritical care: Critical illness, delirium and cognitive impairment.

PMID- 24275930
TI  - Multiple sclerosis: Oral laquinimod for MS--bringing the brain into focus.

PMID- 24275931
TI  - Neurodegenerative disease: C9orf72 RNA foci--a therapeutic target for ALS and
      FTD?

PMID- 24275932
TI  - [Decision of the European Medicines Agency on hydroxyethyl starch : Important
      step towards therapeutic and legal security].

PMID- 24275933
TI  - [Pharmacogenetics. Clinical relevance in anesthsiology].
AB  - BACKGROUND: Pharmacogenetics deals with hereditary factors which influence the
      pharmacodynamics and pharmacokinetics of drugs leading to individual diverse
      reactions. Also in anesthesiology differences in the pharmacogenetics of patients
      can lead to relevant alterations in the pharmacodynamics of drugs. AIM: This
      article provides a summary of polymorphisms relevant to commonly used anesthetic
      agents and the clinical relevance in patients treated with these compounds. It
      describes the possibilities, the problems and limits of pharmacogenetic
      diagnostics and therapy and explains how this follows the target of
      individualized medicine. MATERIAL AND METHODS: This article describes in detail
      the alterations in pharmacodynamics and pharmakokinetics relevant for anesthesia
      and their clinical significance. Based on the results of current studies, an
      overview of the most important drugs in anesthesiology with significant
      polymorphisms is given. These include opioids, muscle relaxants, volatile
      anesthetic agents, non-steroidal anti-inflammatory drugs (NSAIDs),
      benzodiazepines, antiemetics and cardiovascular drugs as well as platelet
      aggregation inhibitors, anticoagulants and the so-called new oral anticoagulants.
      RESULTS: Genetic alterations can lead to substantial modifications in the
      effectiveness of drugs. Genetic alterations of opioid receptors and the enzyme
      cytochrome P450 (CYP) 2D6 can result in a failure of analgesia after
      administration of opioids. Alterations in plasma cholinesterase activity are
      associated with a prolonged effectiveness of muscle relaxants. Polymorphisms in
      ryanodine receptors can contribute to the development of the feared MH in
      patients after administration of volatile anesthetics or succinylcholine.
      CONCLUSION: The study results presented here emphasize that these days knowledge
      on pharmacogenetics should not be missing in modern induction of anesthesia. In
      the future a blood sample could enable physicians to identify pharmacologically
      relevant markers. And these could guide the decision on the prescription of drugs
      and their appropriate dose, in order to achieve the lowest risk of side effects
      and the highest effectiveness of the active substance.

PMID- 24275934
TI  - RETRACTED ARTICLE: Different anesthesia methods for laparoscopic cholecystectomy.

PMID- 24275935
TI  - [Ultrasound in interventional pain therapy].
AB  - Peripheral nerve blocks are currently performed relatively blind even in the most
      complex anatomical structures and physicians mostly rely on palpable anatomical
      landmarks on the surface. Ultrasound has become an indispensable part of the
      modern medical world and has long since found its way into almost all medical
      professions. More and more this trend also reaches interventional pain physicians
      as it is possible to accurately target structures, to track the needle course
      during the intervention and to visualize the spread of the local anesthetic.
      Another advantage compared to other radiological techniques is the profound
      radiation safety for patients as well as for personnel performing the
      intervention. A deep understanding of anatomy and its correlate in ultrasound
      images is one of the most important requirements for the successful use of these
      interventional techniques. Moreover, the safe performance of the procedure
      depends on the simultaneous hand-eye coordination. Nevertheless, despite the
      euphoria ultrasound technology should only be used in pain management with
      sufficient indications. 

PMID- 24275936
TI  - Perioperative hypertension: white coat, masked, and appropriately referred for
      treatment.

PMID- 24275938
TI  - Alternative BIS montage positions: caution still warranted.

PMID- 24275939
TI  - Can preoperative betaxolol eye drops reduce the incidence of postoperative visual
      loss (POVL)?

PMID- 24275940
TI  - Dual effects of ketamine: neurotoxicity versus neuroprotection in anesthesia for
      the developing brain.
AB  - Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used in
      pediatric anesthesia. Recently, a series of animal studies have shown that
      ketamine may have neurotoxic effects on the developing brain and that these
      effects can later cause neurofunctional impairment. However, other studies have
      also shown that ketamine protects the central nervous system by inhibiting
      inflammation in the developing brain. The present study offers a review of the
      existing preclinical and clinical studies. We concluded that the role of ketamine
      varies not only on the basis of the dose and frequency of exposure but also the
      intensity of the noxious stimuli. Moreover, the repeated ketamine usage may be
      neurotoxic to immature brains in the absence of noxious stimuli, whereas it may
      be neuroprotective in the same brains in the presence of strong painful stimuli.
      Balancing the neurotoxic and neuroprotective effects of ketamine on the
      developing brain may be possible, but further study is required. The therapeutic
      window during which precritical surgeries can be performed remains undefined. 

PMID- 24275941
TI  - Genome-wide identification and expression analysis of the mitogen-activated
      protein kinase gene family from banana suggest involvement of specific members in
      different stages of fruit ripening.
AB  - Mitogen-activated protein kinases (MAPKs) are important components of the
      tripartite mitogen-activated protein kinase signaling cascade and play an
      important role in plant growth and development. Although members of the MAPK gene
      family have been identified in model plants, little information is available
      regarding this gene family in fruit crops. In this study, we carried out a
      computational analysis using the Musa Genome database to identify members of the
      MAPK gene family in banana, an economically important crop and the most popular
      fruit worldwide. Our analysis identified 25 members of the MAP kinase (MAPK or
      MPK) gene family. Phylogenetic analyses of MPKs in Arabidopsis, Oryza, and
      Populus have classified these MPKs into four subgroups. The presence of conserved
      domains in the deduced amino acid sequences, phylogeny, and genomic organization
      strongly support their identity as members of the MPK gene family. Expression
      analysis during ethylene-induced banana fruit ripening suggests the involvement
      of several MPKs in the ethylene signal transduction pathway that are necessary
      for banana fruit ripening. Analysis of the cis-regulatory elements in the
      promoter regions and the involvement of the identified MPKs in various cellular
      processes, as analyzed using Pathway Studio, suggest a role for the banana MPK
      gene family in diverse functions related to growth, development, and the stress
      response. This report is the first concerning the identification of members of a
      gene family and the elucidation of their role in various processes using the Musa
      Genome database. 

PMID- 24275942
TI  - CNBP regulates wing development in Drosophila melanogaster by promoting IRES
      dependent translation of dMyc.
AB  - CCHC-type zinc finger nucleic acid binding protein (CNBP) is a small conserved
      protein, which plays a key role in development and disease. Studies in animal
      models have shown that the absence of CNBP results in severe developmental
      defects that have been mostly attributed to its ability to regulate c-myc mRNA
      expression. Functionally, CNBP binds single-stranded nucleic acids and acts as a
      molecular chaperone, thus regulating both transcription and translation.   In
      this work we report that in Drosophila melanogaster, CNBP is an essential gene,
      whose absence causes early embryonic lethality. In contrast to what observed in
      other species, ablation of CNBP does not affect dMyc mRNA expression, whereas the
      protein levels are markedly reduced. We demonstrate for the first time that dCNBP
      regulates dMyc translation through an IRES-dependent mechanism, and that
      knockdown of dCNBP in the wing territory causes a general reduction of wing size,
      in keeping with the reported role of dMyc in this region. Consistently,
      reintroduction of dMyc in CNBP-deficient wing imaginal discs rescues the wing
      size, further supporting a key role of the CNBP-Myc axis in this context.
      Collectively, these data show a previously uncharacterized mechanism, whereby, by
      regulating dMyc IRES-dependent translation, CNBP controls Drosophila wing
      development. These results may have relevant implications in other species and in
      pathophysiological conditions. 

PMID- 24275943
TI  - Progressive parkinsonism, balance difficulties, and supranuclear gaze palsy.
AB  - A 76-year-old man presented with a 4-year history of a progressive parkinsonian
      syndrome. It started with slowness of gait and mood dysfunction. Symptoms slowly
      progressed and further included occasional unexplained falls. On examination, he
      showed a severe parkinsonian syndrome featuring bradykinesia, rigidity (axial >
      appendicular), and positive pull-test finding. Moreover, there was an upgaze
      supranuclear palsy and slow saccades on vertical plane. Magnetic resonance
      imaging was performed that revealed significant basal ganglia lesions and white
      matter hyperintensities, including periventricular regions and both frontal and
      temporal subcortical areas, along with moderate widespread atrophy and
      ventricular enlargement. Here, we reveal the pathological diagnosis and discuss
      the approach to the clinical data. 

PMID- 24275944
TI  - Deprotonation induced formation of Mobius aromatic [32]heptaphyrins.
AB  - Upon treatment with tetrabutylammonium fluoride (TBAF), [32]heptaphyrins 1 and 2
      underwent conformational changes to form Mobius aromatic species, as indicated by
      the appearance of sharp and intense B-like bands and distinct Q-like bands, long
      lived S1-states, and relatively large TPA cross-section values. Hence,
      deprotonation has been shown to be an additional effective means to induce the
      formation of Mobius aromatic expanded porphyrins. 

PMID- 24275947
TI  - Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake
      of Non-Covalent Complexes into Live Cells.
AB  - Modulating signaling pathways for research and therapy requires either
      suppression or expression of selected genes or internalization of proteins such
      as enzymes, antibodies, nucleotide binding proteins or substrates including
      nucleoside phosphates and enzyme inhibitors. Peptides, proteins and nucleotides
      are transported by fusing or conjugating them to cell penetrating peptides or by
      formation of non-covalent complexes. The latter is often preferred because of
      easy handling, uptake efficiency and auto-release of cargo into the live cell. In
      our studies complexes are formed with labeled or readily detectable cargoes for
      qualitative and quantitative estimation of their internalization. Properties and
      behavior of adhesion and suspension vertebrate cells as well as the protozoa
      Leishmania tarentolae are investigated with respect to proteolytic activity,
      uptake efficiency, intracellular localization and cytotoxicity. Our results show
      that peptide stability to membrane-bound, secreted or intracellular proteases
      varies between different CPPs and that the suitability of individual CPPs for a
      particular cargo in complex formation by non-covalent interactions requires
      detailed studies. Cells vary in their sensitivity to increasing concentrations of
      CPPs. Thus, most cells can be efficiently transduced with peptides, proteins and
      nucleotides with intracellular concentrations in the low micromole range. For
      each cargo, cell type and CPP the optimal conditions must be determined
      separately. 

PMID- 24275945
TI  - siRNA Genome Screening Approaches to Therapeutic Drug Repositioning.
AB  - Bridging high-throughput screening (HTS) with RNA interference (RNAi) has allowed
      for rapid discovery of the molecular basis of many diseases, and identification
      of potential pathways for developing safe and effective treatments. These
      features have identified new host gene targets for existing drugs paving the
      pathway for therapeutic drug repositioning. Using RNAi to discover and help
      validate new drug targets has also provided a means to filter and prioritize
      promising therapeutics. This review summarizes these approaches across a spectrum
      of methods and targets in the host response to pathogens. Particular attention is
      given to the utility of drug repurposing utilizing the promiscuous nature of some
      drugs that affect multiple molecules or pathways, and how these biological
      pathways can be targeted to regulate disease outcome. 

PMID- 24275948
TI  - Elucidating the function of penetratin and a static magnetic field in cellular
      uptake of magnetic nanoparticles.
AB  - Nanotechnology plays an increasingly important role in the biomedical arena. In
      particular, magnetic nanoparticles (mNPs) have become important tools in
      molecular diagnostics, in vivo imaging and improved treatment of disease, with
      the ultimate aim of producing a more theranostic approach. Due to their small
      sizes, the nanoparticles can cross most of the biological barriers such as the
      blood vessels and the blood brain barrier, thus providing ubiquitous access to
      most tissues. In all biomedical applications maximum nanoparticle uptake into
      cells is required. Two promising methods employed to this end include
      functionalization of mNPs with cell-penetrating peptides to promote efficient
      translocation of cargo into the cell and the use of external magnetic fields for
      enhanced delivery. This study aimed to compare the effect of both penetratin and
      a static magnetic field with regards to the cellular uptake of 200 nm magnetic
      NPs and determine the route of uptake by both methods. Results demonstrated that
      both techniques increased particle uptake, with penetratin proving more cell
      specific. Clathrin- medicated endocytosis appeared to be responsible for uptake
      as shown via PCR and western blot, with Pitstop 2 (known to selectively block
      clathrin formation) blocking particle uptake. Interestingly, it was further shown
      that a magnetic field was able to reverse or overcome the blocking, suggesting an
      alternative route of uptake. 

PMID- 24275946
TI  - Dendrimers for siRNA Delivery.
AB  - Since the discovery of the "starburst polymer", later renamed as dendrimer, this
      class of polymers has gained considerable attention for numerous biomedical
      applications, due mainly to the unique characteristics of this macromolecule,
      including its monodispersity, uniformity, and the presence of numerous
      functionalizable terminal groups. In recent years, dendrimers have been studied
      extensively for their potential application as carriers for nucleic acid
      therapeutics, which utilize the cationic charge of the dendrimers for effective
      dendrimer-nucleic acid condensation. siRNA is considered a promising, versatile
      tool among various RNAi-based therapeutics, which can effectively regulate gene
      expression if delivered successfully inside the cells. This review reports on the
      advancements in the development of dendrimers as siRNA carriers. 

PMID- 24275949
TI  - RNAi Therapeutic Platforms for Lung Diseases.
AB  - RNA interference (RNAi) is rapidly becoming an important method for analyzing
      gene functions in many eukaryotes and holds promise for the development of
      therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs,
      which affect specific messenger RNA (mRNA) degradation. Two types of small RNA
      molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are
      central to RNAi. Drug discovery studies and novel treatments of siRNAs are
      currently targeting a wide range of diseases, including various viral infections
      and cancers. Lung diseases in general are attractive targets for siRNA
      therapeutics because of their lethality and prevalence. In addition, the lung is
      anatomically accessible to therapeutic agents via the intrapulmonary route.
      Recently, increasing evidence indicates that miRNAs play an important role in
      lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are
      being targeted for therapeutic purposes. In this review, we present strategies
      for RNAi delivery and discuss the current state-of-the-art RNAi-based
      therapeutics for various lung diseases. 

PMID- 24275950
TI  - NMDA Receptor Modulators in the Treatment of Drug Addiction.
AB  - Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate
      (NMDA) glutamate receptor subtype serves as a molecular target for several drugs
      of abuse. In this review, we will provide an overview of NMDA receptor structure
      and function, followed by a review of the mechanism of action, clinical efficacy,
      and side effect profile of NMDA receptor ligands that are currently in use or
      being explored for the treatment of drug addiction. These ligands include the
      NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA
      agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor
      modulators have relatively limited efficacy in the treatment of drug addiction,
      and that partial agonism of NMDA receptors may have some efficacy with regards to
      extinction learning during cue exposure therapy. However, the lack of consistency
      in results to date clearly indicates that additional studies are needed, as are
      studies examining novel ligands with indirect mechanisms for altering NMDA
      receptor function. 

PMID- 24275951
TI  - cGMP-Dependent Protein Kinase Inhibitors in Health and Disease.
AB  - cGMP-dependent protein kinases (PKG) exhibit diverse physiological functions in
      the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in
      platelets, in kidney, in bone growth, nociception and in the central nervous
      system. Furthermore, PKG were found in insects and in the malaria parasite
      Plasmodium falciparum. Two different genes of PKG exist: a) the PKG-I gene that
      is expressed as cytosolic PKG-Ialpha or PKG-Ibeta isoform, and b) the PKG-II
      gene, which expresses the membrane associated PKG-II protein. The enzyme
      kinetics, the localization and the substrates of these PKG enzymes differ
      utilizing different physiological functions. Various inhibitors of PKG were
      developed directed against diverse functional regions of the kinase. These
      inhibitors of PKG have been used to analyse the specific functions of these
      enzymes. The review article will summarize these different inhibitors regarding
      their specificity and their present applications in vitro and in vivo.
      Furthermore, it will be discussed that the distinct inhibition of the PKG enzymes
      could be used as a valuable pharmacological target e.g., in the treatment of
      cardiovascular diseases, diarrhea, cancer or malaria. 

PMID- 24275952
TI  - Relativistic and thermal effects on the magnon spectrum of a ferromagnetic
      monolayer.
AB  - A spin model including magnetic anisotropy terms and Dzyaloshinsky-Moriya
      interactions is studied for the case of a ferromagnetic monolayer with C2v
      symmetry like Fe/W(110). Using the quasiclassical stochastic Landau-Lifshitz
      Gilbert equations, the magnon spectrum of the system is derived using linear
      response theory. The Dzyaloshinsky-Moriya interaction leads to asymmetry in the
      spectrum, while the anisotropy terms induce a gap. It is shown that, in the
      presence of lattice defects, both the Dzyaloshinsky-Moriya interactions and the
      two-site anisotropy lead to a softening of the magnon energies. Two methods are
      developed to investigate the magnon spectrum at finite temperatures. The
      theoretical results are compared to atomistic spin dynamics simulations and good
      agreement is found between them. 

PMID- 24275953
TI  - Multicenter, randomized trial of quantitative pretest probability to reduce
      unnecessary medical radiation exposure in emergency department patients with
      chest pain and dyspnea.
AB  - BACKGROUND: Use of pretest probability can reduce unnecessary testing. We
      hypothesize that quantitative pretest probability, linked to evidence-based
      management strategies, can reduce unnecessary radiation exposure and cost in low
      risk patients with symptoms suggestive of acute coronary syndrome and pulmonary
      embolism. METHODS AND RESULTS: This was a prospective, 4-center, randomized
      controlled trial of decision support effectiveness. Subjects were adults with
      chest pain and dyspnea, nondiagnostic ECGs, and no obvious diagnosis. The
      clinician provided data needed to compute pretest probabilities from a Web-based
      system. Clinicians randomized to the intervention group received the pretest
      probability estimates for both acute coronary syndrome and pulmonary embolism and
      suggested clinical actions designed to lower radiation exposure and cost. The
      control group received nothing. Patients were followed for 90 days. The primary
      outcome and sample size of 550 was predicated on a significant reduction in the
      proportion of healthy patients exposed to >5 mSv chest radiation. A total of 550
      patients were randomized, and 541 had complete data. The proportion with >5 mSv
      to the chest and no significant cardiopulmonary diagnosis within 90 days was
      reduced from 33% to 25% (P=0.038). The intervention group had significantly lower
      median chest radiation exposure (0.06 versus 0.34 mSv; P=0.037, Mann-Whitney U
      test) and lower median costs ($934 versus $1275; P=0.018) for medical care.
      Adverse events occurred in 16% of controls and 11% in the intervention group
      (P=0.06). CONCLUSIONS: Provision of pretest probability and prescriptive advice
      reduced radiation exposure and cost of care in low-risk ambulatory patients with
      symptoms of acute coronary syndrome and pulmonary embolism. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01059500.

PMID- 24275954
TI  - Investigation of global and regional myocardial mechanics with 3-dimensional
      speckle tracking echocardiography and relations to hypertrophy and fibrosis in
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: In hypertrophic cardiomyopathy (HCM), heterogeneous myocardial
      hypertrophy and fibrosis are responsible for abnormalities of left ventricular
      (LV) function. We aimed to characterize LV global and regional myocardial
      mechanics in HCM, according to segmental hypertrophy and fibrosis. METHODS AND
      RESULTS: Fifty-nine patients with HCM underwent standard echocardiography, 3
      dimensional speckle tracking echocardiography, and cardiac magnetic resonance
      with late gadolinium enhancement (LGE); all 3 tests were <24 hours apart.
      Longitudinal, circumferential, and area strains were investigated according to
      the extent of LGE (no LGE, LGE<10%, and LGE>=10%), segmental thickness (>=15
      versus <15 mm), and segmental LGE (LGE versus non-LGE). Attenuated global
      longitudinal strain showed association with extent of hypertrophy (indexed LV
      mass, r=0.32, P=0.01; maximum LV wall thickness, r=0.34, P=0.009; number of
      segments>=15 mm, r=0.44, P<0.001), whereas enhanced global circumferential strain
      was correlated to LV global functional parameters (indexed end-systolic volume,
      r=0.47, P<0.001; ejection fraction, r=-0.75, P<0.001). Parameters of global
      myocardial mechanics showed no association with the extent of LGE; in contrast,
      the extent of LGE was associated with the extent of hypertrophy. All 3
      deformation parameters were attenuated both in segments>=15 mm in thickness and
      in those with LGE; adjusted analysis demonstrated that segmental presence of LGE
      was associated with additional attenuation in myocardial deformation.
      CONCLUSIONS: Both hypertrophy and fibrosis contribute to regional impairment of
      myocardial shortening in HCM. The extent of hypertrophy is the primary factor
      altering global myocardial mechanics. Circumferential myocardial shortening seems
      to be directly involved in preservation of LV systolic performance in HCM.

PMID- 24275955
TI  - Prognostic value of cardiovascular magnetic resonance imaging measurements
      corrected for age and sex in idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: There are limited data on the prognostic value of cardiovascular
      magnetic resonance measurements in idiopathic pulmonary arterial hypertension,
      with no studies investigating the impact of correction of cardiovascular magnetic
      resonance indices for age and sex on prognostic value. METHODS AND RESULTS:
      Consecutive patients with idiopathic pulmonary arterial hypertension underwent
      cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession
      cardiac volumes and mass measurements were corrected for age, sex, and body
      surface area according to reference data and prognostic significance assessed. A
      total of 80 patients with idiopathic pulmonary arterial hypertension were
      identified, and 23 patients died during the mean follow-up of 32+/-14 months.
      Corrected for age, sex, and body surface area, right ventricular end-systolic
      volume (P=0.004) strongly predicted mortality, independent of World Health
      Organization functional class, mean right atrial pressure, cardiac index, and
      mixed venous oxygen saturations. CONCLUSIONS: Consideration should be given to
      correcting cardiovascular magnetic resonance measures for age, sex, and body
      surface area, particularly given the changing demographics of patients with
      idiopathic pulmonary arterial hypertension. Corrected right ventricular end
      systolic volume is a strong prognostic marker in idiopathic pulmonary arterial
      hypertension, independent of invasively derived measurements, mean right atrial
      pressure cardiac index, and mixed venous oxygen saturations.

PMID- 24275956
TI  - Effects of switching from NPH insulin to insulin glargine in patients with type 2
      diabetes: the retrospective, observational LAUREL study in Italy.
AB  - The aim was to observe the effects of switching from neutral protamine Hagedorn
      (NPH) insulin to insulin glargine on glycaemic control in patients with type 2
      diabetes mellitus (T2DM) in everyday clinical practice in Italy. This
      multicenter, observational, retrospective study included 1,011 patients with T2DM
      who switched from NPH insulin to glargine or were maintained on NPH insulin. The
      primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included
      fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to
      treat population consisted of 996 patients (glargine 496; NPH 500). Prior to
      switching, HbA1c was higher in the glargine than the NPH group [mean (+/-SD) 8.8
      +/- 1.4 vs. 7.9 +/- 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with
      glargine (8.2 +/- 1.4%; p < 0.001) but not with NPH (8.0 +/- 1.4%; p = 0.20).
      Similar results were observed for FBG. The daily dose of glargine increased from
      0.22 +/- 0.10 U/kg at the switch to 0.26 +/- 0.11 U/kg at study end, while the
      NPH dose remained stable (0.19 +/- 0.09-0.20 +/- 0.09 U/kg). While not
      statistically significant, the percentage of patients with hypoglycaemic episodes
      during the last month of treatment tended to be less with glargine. No
      significant change in body weight occurred in either group. Switching patients
      from NPH insulin to insulin glargine in a real-life setting was associated with
      significant improvement in glycaemic control. The increase in glargine dose was
      not accompanied by increased hypoglycaemia or weight gain.

PMID- 24275957
TI  - Platelet-rich plasma: why intra-articular? A systematic review of preclinical
      studies and clinical evidence on PRP for joint degeneration.
AB  - PURPOSE: The aim of this review was to analyze the available evidence on the
      clinical application of this biological approach for the injective treatment of
      cartilage lesions and joint degeneration, together with preclinical studies to
      support the rationale for the use of platelet concentrates, to shed some light
      and give indications on what to treat and what to expect from intra-articular
      injections of platelet-rich plasma (PRP). METHODS: All in vitro, in vivo
      preclinical and clinical studies on PRP injective treatment in the English
      language concerning the effect of PRP on cartilage, synovial tissue, menisci, and
      mesenchymal stem cells were considered. A systematic review on the PubMed
      database was performed using the following words: (platelet-rich plasma or PRP or
      platelet concentrate or platelet lysate or platelet supernatant) and (cartilage
      or chondrocytes or synoviocytes or menisci or mesenchymal stem cells). RESULTS:
      Fifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo,
      2 were both in vivo and in vitro, and 22 were clinical studies. The analysis
      showed an increasing number of published studies over time. Preclinical evidence
      supports the use of PRP injections that might promote a favourable environment
      for joint tissues healing. Only a few high-quality clinical trials have been
      published, which showed a clinical improvement limited over time and mainly
      documented in younger patients not affected by advanced knee degeneration.
      CONCLUSIONS: Besides the limits and sometimes controversial findings, the
      preclinical literature shows an overall support toward this PRP application. An
      intra-articular injection does not just target cartilage; instead, PRP might
      influence the entire joint environment, leading to a short-term clinical
      improvement. Many biological variables might influence the clinical outcome and
      have to be studied to optimize PRP injective treatment of cartilage degeneration
      and osteoarthritis.

PMID- 24275959
TI  - Fifteen years of experience with the midfacial distraction without maxillary
      osteotomy protocol.
AB  - PURPOSE: Midfacial distraction for facial stenosis is minimizing the
      communication between cranial fossa and nasal fossa caused by the Le Fort III
      osteotomy during frontofacial advancement procedures. There are different types
      of distractors, such as internal and external devices. The aim of our study is to
      present a series of 22 consecutive distraction cases operated without any Le Fort
      osteotomy with external distraction frames. We completely avoid the gap between
      the skull and nose, thus avoiding related complications. PATIENTS AND METHODS:
      Between 1997 and 2012, we operated on 22 patients presenting syndromes
      associating midfacial retrusion, maxillomandibular class III malocclusion and
      upper airway obstruction. METHODS: We perform a fronto-orbital advancement. We do
      not perform any maxillary osteotomy. A vertical cut in the lateral orbital wall
      is done towards the inferior orbital fissure and another cut on the zygomatic
      arch. We realise the fixation of the frame posteriorly with a folded K-wire and
      anteriorly with a transmaxillary pin. Aiming overcorrection, we distract on
      average 1 mm a day for a mean period of 26 days and with a horizontal distraction
      vector. RESULTS: No deaths or life-threatening complications were reported. All
      midfacial retrusions were corrected without relapse. The advancement ranged
      between 6 and 20 mm. Several complications were notified: one sphenopetrous
      dislocation, one ethmoidonasal dislocation, two device disassemblages and two
      cases of maxillary sinusitis. Some of these complications caused an incomplete
      distraction result. CONCLUSIONS: Compared to other techniques, this method is
      safe, simple and efficient. By sparing major osteotomies, it avoids severe
      complications.

PMID- 24275958
TI  - Analysis of a bleeding mechanism in patients with the sylvian arachnoid cyst
      using a finite element model.
AB  - OBJECTIVE: The sylvian arachnoid cyst (AC) is a common benign disease; however,
      it sometimes leads to subdural or intracystic hemorrhage without major trauma.
      The reason of easy bleeding of the AC is not fully understood. The purpose of
      this study was to investigate the bleeding mechanism of the sylvian AC in
      biomechanical aspect and suggest treatment guidelines. METHODS: A finite element
      (FE) model of normal male adult head/brain was developed and validated by
      comparison with cadaveric experimental studies. Based on the normal FE model, two
      sylvian AC models with different sizes (mean size, 55.5 cm(3); large size, 75.2
      cm(3)) were developed. To simulate the interface between the dura mater and the
      arachnoid membrane, spot-weld constraints were assigned. The vulnerability of
      vein rupture was forecasted with calculated shear force at the spot-weld elements
      (SFSW). Simulation was performed for four different loading directions. RESULTS:
      The newly developed normal FE models showed reliable biomechanical responses
      comparable with the cadaveric experiments. The sylvian AC model showed
      significantly increased SFSW compared with normal model. As AC size increased,
      higher shear force was generated at the spot-weld element of outer wall of
      sylvian AC regardless of impact directions. CONCLUSION: Outer wall of sylvian AC
      receives higher shear force comparing with normal brain, which is a possible
      cause of vulnerability to bleeding. Although the size-reducing surgery may
      decrease bleeding risk of sylvian AC, clinicians need to consider the rare
      incidence of AC bleeding and unsatisfactory volume reduction in many cases of
      fenestration.

PMID- 24275960
TI  - The neural correlates of anomalous habituation to negative emotional pictures in
      borderline and avoidant personality disorder patients.
AB  - OBJECTIVE: Extreme emotional reactivity is a defining feature of borderline
      personality disorder, yet the neural-behavioral mechanisms underlying this
      affective instability are poorly understood. One possible contributor is
      diminished ability to engage the mechanism of emotional habituation. The authors
      tested this hypothesis by examining behavioral and neural correlates of
      habituation in borderline patients, healthy comparison subjects, and a
      psychopathological comparison group of patients with avoidant personality
      disorder. METHOD: During fMRI scanning, borderline patients, healthy subjects,
      and avoidant personality disorder patients viewed novel and repeated pictures,
      providing valence ratings at each presentation. Statistical parametric maps of
      the contrasts of activation during repeated versus novel negative picture viewing
      were compared between groups. Psychophysiological interaction analysis was
      employed to examine functional connectivity differences between groups. RESULTS:
      Unlike healthy subjects, neither borderline nor avoidant personality disorder
      patients exhibited increased activity in the dorsal anterior cingulate cortex
      when viewing repeated versus novel pictures. This lack of an increase in dorsal
      anterior cingulate activity was associated with greater affective instability in
      borderline patients. In addition, borderline and avoidant patients exhibited
      smaller increases in insula-amygdala functional connectivity than healthy
      subjects and, unlike healthy subjects, did not show habituation in ratings of the
      emotional intensity of the images. Borderline patients differed from avoidant
      patients in insula-ventral anterior cingulate functional connectivity during
      habituation. CONCLUSIONS: Unlike healthy subjects, borderline patients fail to
      habituate to negative pictures, and they differ from both healthy subjects and
      avoidant patients in neural activity during habituation. A failure to effectively
      engage emotional habituation processes may contribute to affective instability in
      borderline patients.

PMID- 24275961
TI  - Modifying cellular properties using artificial aptamer-lipid receptors.
AB  - We demonstrate that artificial aptamer-lipid receptors (AR), which anchor on the
      surface of cells, can modify important cellular functions, including protein
      binding, enzymatic activity, and intercellular interactions. Streptavidin (SA)-AR
      modified CEM cells captured the tetravalent SA with one biotin binding site. The
      remaining biotin sites captured biotinylated TDO5 aptamers, which target IgM on
      Ramos cells, to form CEM-Ramos cell assemblies. In another design, thrombin, an
      enzyme involved in blood clotting, was captured by thrombin-AR-modified cells and
      clot formation was visualized. Lastly, hematopoietic stem cell (HSC) mimics were
      modified with a tenascin-C-AR to improve the homing of HSC after an autologous
      bone marrow transplant. Tenascin-C-AR modified cells aggregated to cells in a
      tenascin-C expressing stem cell niche model better than library-AR modified
      cells. Modification of cellular properties using ARs is a one-step, dosable,
      nontoxic, and reversible method, which can be applied to any cell-type with any
      protein that has a known aptamer. 

PMID- 24275962
TI  - Gout in 2013. Imaging, genetics and therapy: gout research continues apace.
AB  - In 2013, much progress has occurred in gout research. Imaging continues to help
      elucidate aspects of pathophysiology and now suggests that healing of erosions
      could occur when urate levels are reduced dramatically. New genetic loci
      associated with hyperuricaemia have been identified and management strategies for
      prophylaxis of gout flares continue to evolve.

PMID- 24275963
TI  - Fracture repair: Could blockade of Notch signalling promote fracture repair?

PMID- 24275964
TI  - Rheumatoid arthritis: Prevotella copri associated with new-onset untreated RA.

PMID- 24275967
TI  - The ultrastructure of anthocyanoplasts in red-cabbage.
AB  - A study of the ultrastructure of anthocyanoplasts from the seedling hypocotyl and
      leaves from the heart of red-cabbage plants has been made. Evidence is presented
      that the anthocyanoplast does not represent a hydrophobic droplet but is bounded
      by a single tripartite membrane approximately 10 nm in thickness. The results
      provide further support for the view that the anthocyanoplast is an intracellular
      compartment containing at least the later enzymes of anthocyanin biosynthesis,
      which are thereby separated from the hostile acidic environment of the vacuolar
      sap. 

PMID- 24275965
TI  - Standardization of autoantibody testing: a paradigm for serology in rheumatic
      diseases.
AB  - Autoantibody measurement is an excellent tool to confirm the diagnosis of
      rheumatic autoimmune diseases. Hence, reliability and harmonization of
      autoantibody testing are essential, but these issues are still a matter of
      debate. Intrinsic variability in analytes and reagents as well as heterogeneity
      of the techniques are the main reasons for discrepancies in inter-laboratory
      variations and reporting of test results. This lack of reliability might be
      responsible for wrong or missed diagnoses, as well as additional costs due to
      assay repetition, unnecessary use of confirmatory tests and/or consequent
      diagnostic investigations. To overcome such issues, the standardization of
      autoantibody testing requires efforts on all aspects of the assays, including the
      definition of the analyte, the pre-analytical stages, the calibration method and
      the reporting of results. As part of such efforts, the availability of suitable
      reference materials for calibration and quality control would enable the
      development of a reliable reference system. Strong-positive sera from patients
      have been used as reference materials in most of the autoantibody assays for
      rheumatic diseases; however, antigen-affinity-purified immunoglobulin fractions
      or in some cases reliable monoclonal antibody preparations offer more adequate
      tools for standardization. Systematic assessments of reference materials are
      currently underway, and preliminary results appear to be encouraging. 

PMID- 24275968
TI  - Nodulation of soybean byRhizobium japonicum mutants with altered capsule
      synthesis.
AB  - Spontaneous mutants with altered capsule synthesis were isolated from a marked
      strain of the symbiont,Rhizobium japonicum. Differential centrifugation was used
      to enrich serially for mutants incapable of forming capsules. The desired mutants
      were detected by altered colony morphology and altered ability to bind host plant
      lectin. Three mutants failed to form detectable capsules at any growth phase when
      cultured in vitro or in association with the host (soybean,Glycine max (L.)
      Merr.) roots. These mutants were all capable of nodulating and attaching to
      soybean roots, indicating that the presence of a capsule physically surrounding
      the bacterium is not required for attachment or for infection and nodulation.
      Nodulation by several of the mutants was linearly proportional to the amount of
      acidic exopolysaccharide that they released into the culture medium during the
      exponential growth phase, indicating that such polysaccharide synthesis is
      important and perhaps required for nodulation. Two of the mutants appeared to
      synthesize normal lectin-binding capsules when cultured in association with host
      roots, but not when cultured in vitro. Nodulation by these mutants appeared to
      depend on how rapidly after inoculation they synthesized capsular polysaccharide.

PMID- 24275966
TI  - Juvenile fibromyalgia: current status of research and future developments.
AB  - Juvenile-onset fibromyalgia (JFM) is a poorly understood chronic pain condition
      most commonly affecting adolescent girls. The condition is characterized by
      widespread musculoskeletal pain and other associated symptoms, including fatigue,
      nonrestorative sleep, headaches, irritable bowel symptoms, dysautonomia and mood
      disorders such as anxiety and/or depression. In the past few years, there has
      been a greater focus on understanding JFM in adolescents. Research studies have
      provided insight into the clinical characteristics of this condition and its
      effect on both short-term and long-term psychosocial and physical functioning.
      The importance of early and effective intervention is being recognized, as
      research has shown that symptoms of JFM tend to persist and do not resolve over
      time as was previously believed. Efforts to improve treatments for JFM are
      underway, and new evidence strongly points to the potential benefits of cognitive
      behavioural therapy on improving mood and daily functioning. Research into
      pharmacotherapy and other nonpharmacological options is in progress. Advancements
      in the understanding of adult fibromyalgia have paved the way for future studies
      on diagnosis, assessment and management of JFM. This Review focuses on our
      current knowledge of the condition, provides an update of the latest research
      advances, and highlights areas for further study. 

PMID- 24275969
TI  - Amino-acid transport in suspension-cultured plant cells : V. Influence of L
      leucine, carbon-free and nitrogen-free media on L-leucine uptake.
AB  - The carrier system which transports L-leucine (L-leu) into suspension
      culturedNicotiana tabacum L. cv. Wisconsin 38 cells appeared to be constitutive
      since it was always present and was not induced by L-leu even in nitrogen-starved
      cells. However, L-leu uptake rates for cells grown in medium containing L-leu
      were transiently reduced as a result of either transinhibition or repression.
      Growth-phase cells appeared to have more L-leu carriers per unit area of membrane
      than stationary-phase cells, and for this reason growing-phase cells exhibit
      higher L-leu uptake rates. These higher rates reflect a physiological or
      developmental condition since growth-phase cells did not dramatically change
      their L-leu uptake rates when subcultured, while stationary-phase cells doubled
      their rates within 6 h after being subcultured. Cells grown in a medium lacking a
      useable carbon souce had uptake rates higher than control rates for several days.
      These higher rates peaked after about 1 d and then decreased over the next
      several days. Cells grown in a medium lacking a nitrogen souce responded
      similarly except that the increased rates peaked after about 3 d and persisted
      longer. Kinetic analysis of uptake rates in cells grown without a carbon souce
      for 1 d or without a nitrogen souce for 3 d indicated that the L-leu carrier had
      Kms similar to those of untreated cells. These results indicate that cultured
      tobacco cells respond to their environment by increasing or decreasing the number
      or activity of kinetically similar L-leu carriers. 

PMID- 24275970
TI  - The use and misuse of calcium carbonate as an aid to the spectrophotometric assay
      of phytochrome in vitro.
AB  - Supernatant and resuspended pellet samples from a centrifugation of homogenised,
      etiolated oat seedlings were prepared and assayed spectrophotometrically for
      phytochrome in the presence and absence of added calcium carbonate (CaCO3)
      particles under a variety of conditions. At a constant sample thickness, in the
      absence of CaCO3, increasing sample concentration had no significant effect on
      the expected phytochrome reading. In the presence of CaCO3, however, as sample
      concentration increased, the phytochrome reading was less than, expected more so
      in resuspended pellet samples than in supernatant samples. At a constant sample
      concentration in the absence of CaCO3, increasing sample thickness gave no
      significant difference from the excepted phytochrome reading in supernatant
      samples, but led to a slight increase over the expected phytochrome reading in
      resuspended pellet samples. In the presence of CaCO3, increasing sample thickness
      led to a drop from the expected phytochrome reading in both sample types, but
      more so in resuspended pellet samples. These findings show that the use of CaCO3
      as an aid to spectrophotometric phytochrome assay can lead to large artifacts in
      the instrument reading and that its use should be approached with caution. 

PMID- 24275971
TI  - Integral association of phytochrome with a membranous fraction from
      etiolatedAvena shoots: red/far-red photoreversibility and in vitro
      characterization.
AB  - The results reported in this paper provide strong evidence to support the belief
      that the small percentage of phytochrome recovered in low-speed centrifugation
      pellets, when prepared in the absence of divalent cations after various in vivo
      irradiations, is not simply a manifestation of non-specific co-precipitation of
      soluble phytochrome.The far-red reversibility of the observed near-doubling of
      phytochrome pelletability after in vivo red irradiation indicates that
      phytochrome pelletability in the absence of divalent cations is a phytochrome
      controlled response. The characteristics of the pelleted phytochrome indicate a
      strong, hydrophobic interaction with membranes. A tentative proposal to explain
      the observed characteristics of the association of phytochrome with membranous
      material in the absence of divalent cations after different in vivo irradiations
      has been put forward. 

PMID- 24275972
TI  - Integral association of phytochrome with a membranous fraction fromAvena shoots:
      in vivo characterization and physiological significance.
AB  - Phytochrome in the far-red light absorbing form (Pfr) was observed to disappear
      in vivo more rapidly from the non-cation-requiring pelletable phytochrome
      population than from the supernantant phytochrome population of oat seedlings
      given an increasing dark incubation after red irradiation. The amount of
      pelletable phytochrome in the red light absorbing form (Pr) remained relatively
      stable while supernatant Pr was lost. These observations indicated that supernant
      Pfr was subject to loss during the incubation, while pelletable Pfr was subject
      to both dark reversion and loss.During the incubation, the ability of far-red
      irradiation to reverse the red-induced increase in phytochrome pelletability was
      lost, with kinetics similar to those of the loss of pelletable Pfr.Far-red
      reversibility of the red-induced increase in coleoptile elongation correlated
      with the change intotal Pfr in both supernatant and pelletable phytochrome
      populations, but with the change in the ratio of Pfr to total phytochrome only in
      the pelletable phytochrome population.The possible significance of these results
      is discussed with reference to the action of phytochrome in the photocontrol of
      physiological growth responses. 

PMID- 24275973
TI  - Rapid stomatal responses to humidity.
AB  - The response of leaf conductance in apple to rapid changes in atmospheric
      humidity was studied using a continuous flow porometer. Leaf-air vapour pressure
      difference was changed by adjusting the humidity of the inlet air or by altering
      the flow rate of the air through the chamber. The time course of the response of
      leaf conductance to leaf-air vapour pressure difference was monitored for periods
      up to 10 min using a chart-recorder. There were significant changes in leaf
      conductance within seconds of changing humidity. These were attributed to
      alterations in stomatal aperture. 

PMID- 24275974
TI  - Dormancy in somatic embryos and seeds ofVitis: changes in endogenous abscisic
      acid during embryogeny and germination.
AB  - Abscisic acid (ABA) in extracts of somatic embryos and seeds of Gloryvine (Vitis
      vinifera L.xV. rupestris Scheele) was measured by gas chromatography-mass
      spectrometry-selected ion monitoring using deuterated ABA, (+/-)-[C-3Me
      (2)H3]ABA, ([(2)H3]ABA) as internal standard. The ABA content increased rapidly
      during embryogeny (0.035 ng/embryo at the globular stage to 0.22 ng/embryo at the
      mature stage). The level of ABA in the tissues of somatic embryos, expressed in
      ng/mg dry weight, decreased from the globular stage (0.76 ng/mg) to the mature
      stage (0.25 ng/mg). Chilling (4 degrees  C) induced normal germination of seeds
      and mature somatic embryos and precocious germination of globular, heart-shaped
      and torpedoshaped somatic embryos. In all cases chilling led to a marked
      reduction in endogenous ABA. Exogenous (+/-)-ABA inhibited the germination of
      chilled somatic embryos. 

PMID- 24275975
TI  - Oxidation of acetate, acetyl CoA and acetylcarnitine by pea mitochondria.
AB  - Acetylcarnitine was rapidly oxidised by pea mitochondria. (-)-carnitine was an
      essential addition for the oxidation of acetate or acetyl CoA. When acetate was
      sole substrate, ATP and Mg(2+) were also essential additives for maximum
      oxidation. CoASH additions inhibited the oxidation of acetate, acetyl CoA and
      acetylcarnitine. It was shown that CoASH was acting as a competitive inhibitor of
      the carnitine stimulated O2 uptake. It is suggested that acetylcarnitine and
      carnitine passed through the mitochondrial membrane barrier with ease but acetyl
      CoA and CoA did not. Carnitine may also buffer the extra- and intra-mitochondrial
      pools of CoA. The presence of carnitine acetyltransferase (EC 2.3.1.7) on the pea
      mitochondria is inferred. 

PMID- 24275976
TI  - Light-controlled inhibition of hypocotyl growth inSinapis alba L. seedlings :
      Fluence rate dependence of hourly light pulses and continuous irradiation.
AB  - Fluence rate-response curves were determined for the inhibition of hypocotyl
      growth in 54 h old dark-grownSinapis alba L. seedlings by continuous or hourly 5
      min red light irradiation (24 h). In both cases a fluence rate-dependence was
      observed. More than 90% of the continuous light effect could be substituted for
      by hourly light pulses if the total fluence of the two different light regimes
      was the same. Measurements of the far red absorbing form of phytochrome ([P fr])
      and [P fr]/[P tot] (total phytochrome) showed a strong fluence rate-dependence
      under continuous and pulsed light which partially paralleled the fluence rate
      response curves for the inhibition of the hypocotyl growth. 

PMID- 24275977
TI  - Differential patterns of phytoalexin accumulation and enzyme induction in wounded
      and elicitor-treated tissues ofPhaseolus vulgaris.
AB  - In wounded cotyledons ofPhaseolus vulgaris L. the accumulation of the 5-hydroxy
      isoflavonoids kievitone and 2'-hydroxygenistein precedes the major increases in
      the levels of the 5-deoxy compounds phaseollin and coumestrol. Increased
      phytoalexin levels are preceded by transient increases in the extractable
      activities of L-phenylalanine ammonia-lyase (EC 4.3.1.5.), chalcone synthase and
      chalcone isomerase (EC 5.5.1.6.). Accumulation of phytoalexins, above wounded
      control levels, is observed following treatment of excised cotyledons or
      hypocotyls with crude or fractionated elicitor preparations heat-released from
      the cell walls ofColletotrichum lindemuthianum. Chalcone synthase levels are also
      induced in cotyledons, although crude elicitor and all fractions suppress L
      phenylalanine ammonia-lyase activity in both tissues. Kievitone is the major
      phytoalexin induced in cotyledons, whereas in hypocotyls phaseollin predominates.
      Patterns of phytoalexin accumulation have been studied in response to varying
      concentrations of the crude and fractionated elicitor; 5-hydroxy isoflavonoid
      accumulation is highly dependent upon elicitor concentration, the dose-response
      curves for kievitone accumulation showing maxima at around 1 MUg glucose
      equivalents per cotyledon, minima at 2-3 MUg equivalents and increasing induction
      at higher concentrations. Similar patterns are observed for L-phenylalanine
      ammonia-lyase and chalcone synthase levels, although the overall extent of these
      changes is masked by the high wound response. Accumulation of 5-deoxy
      isoflavonoids above control levels requires high elicitor concentrations; no
      experimental conditions were found under which phaseollin accumulated to higher
      levels than kievitone in cotyledons during the first 48 h after elicitation. 

PMID- 24275978
TI  - A peroxisomal glycolate oxidase in the algaMougeotia.
AB  - Microbodies of the algaMougeotia were isolated in a linear sucrose gradient. The
      organelles, which moved to the density 1.24 g cm(-3), contained about 70% of the
      glycolate oxidase (EC 1.1.3.1) found in this alga. The enzyme oxidized glycolate,
      utilizing either oxygen or 2,6-dichlorophenolindophenol (DCPIP) as the electron
      acceptor. L-Lactate was an alternate substrate; almost no D-lactate was utilized.
      In the presence of O2, a Km of 415 MUM was determined for glycolate, whereas the
      Km for L-lactate was about 5,000 MUM. In the presence of DCPIP, lower
      concentrations of glycolate and L-lactate were sufficient to obtain the highest
      rates of enzyme activity. 

PMID- 24275979
TI  - The action of exogenous gibberellic acid on protein and mRNA in germinating
      castor bean seeds.
AB  - Gibberellic acid (GA3) stimulates water uptake in castor beans and increases the
      activity of certain enzymes associated with lipid mobilisation.The effect of the
      GA3 on the enzymes is possibly due to a general effect of the growth substance on
      protein synthesis. Gibberellic acid advanced the appearance of rRNA and poly
      (A(+))RNA in castor bean endosperms without specifically stimulating the
      synthesis of particular mRNA species. Thus these increased levels of mRNA and
      rRNA may act synergistically to affect the rate of a predetermined pattern of
      protein synthesis. 

PMID- 24275980
TI  - The action of exogenous gibberellic acid on isocitrate lyase -mRNA in germinating
      castor bean seeds.
AB  - Gibberellic acid (GA3) stimulates isocitrate lyase activity of the endosperm
      during germination of castor bean seeds. Isocitrate lyase from castor bean was
      purified and an antibody to it was prepared from rabbit serum. This antibody was
      used to measure the amounts of isocitrate lyase-mRNA using an in vitro
      translation system. No specific stimulation of isocitrate lyase-mRNA by
      application of GA3 was detected. The stimulation of isocitrate lyase activity by
      exogenous GA3 may be accounted for by the action of the growth substance in
      advancing the overall production of rRNA and mRNA which accelerates the rate of
      total protein synthesis during germination. The application of Amo 1618 retards
      the production of isocitrate lyase activity but also retards protein synthesis in
      general. This suggests that endogenous gibberellins also act non-specifically in
      the regulation of protein synthesis during castor bean germination. 

PMID- 24275981
TI  - Rice protein-body formation: all types are initiated by dilation of the
      endoplasmic reticulum.
AB  - The ultrastructure of protein deposition in the starchy endosperm of developing
      rice (Oryza sativa L.) grains was examined in conventionally fixed
      (glutaraldehyde and osmium tetroxide) tissues and also in thick sections (0.3
      MUm) of zinc iodide-osmium tetroxide post-fixed tissue. Three types of previously
      characterised protein body were observed and it was shown that each type was
      initiated by dilations of the endoplasmic reticulum. Crystalline type protein
      bodies were initiated by a ribosome-free dilation from rough cisternal
      endoplasmic reticulum and developed by inclusion of protein from dictyosome
      derived vesicles. The large spherical and small spherical protein bodies
      developed within the cisternae of the rough endoplasmic reticulum. 

PMID- 24275982
TI  - Light-enhanced perception of gravity in stems of intact pea seedlings.
AB  - Dark-grown, 6-d-old pea seedlings (Pisum sativum L. cv. Alaska) do not respond
      gravitropically to brief (approx. 3 min) horizontal presentations, but seedlings
      given a pulse of red light (R) 16-24 h earlier respond to such stimuli by
      vigorous curvature of the epicotyl. With continuous horizontal stimulation
      (approx. 100 min), the kinetics and extent of the gravitropic response are almost
      identical in irradiated and dark-control plants. Prior R thus increases
      graviperception without altering the rate-limiting steps underlying the
      generation of curvature. This effect of R on graviperception develops slowly;
      seedlings studied only a few hours after R show differences in the kinetics of
      the gravitropic response, but not in presentation time. Neither the kinetics nor
      the extent of gravitropic curvature should be used as criteria for establishing
      changes in primary processes in gravitropism. 

PMID- 24275983
TI  - Optical coherence tomography and visual field findings in patients with
      Friedreich ataxia.
AB  - BACKGROUND: To investigate the optical coherence tomography (OCT) and visual
      field findings in Friedreich ataxia (FRDA). METHODS: Ten eyes of 10 patients with
      genetically confirmed FRDA were included in this study. Twenty-two eyes of 22 age
      and sex-matched volunteers served as controls. All eyes were examined with
      spectral domain OCT (Retinascan Advanced RS-3000; NIDEK) and Humphrey Field
      Analyzer (HFA II 750; Zeiss-Humphrey Systems). RESULTS: OCT measurements of the
      average peripapillary retinal nerve fiber layer (RNFL) thickness, average
      peripapillary retinal thickness (RT), and foveal RT showed a statistically
      significant reduction in patients with FRDA (P < 0.0001). There was no
      statistically significant difference in choroidal thickness. OCT measurements of
      horizontal cup-to-disc (C/D) ratio, vertical C/D ratio, and average cup area were
      significantly increased in patients with FRDA. Visual acuity was significantly
      correlated with age at onset (P = 0.021) and average RNFL value (P = 0.045).
      There was a significant correlation between foveal thickness and disease duration
      (P = 0.014). Mean RNFL thickness was significantly correlated with the severity
      of neurological involvement (P = 0.039). Visual field testing (VFT) revealed a
      generalized reduction of sensitivity in the patients. CONCLUSION: Patients with
      FRDA may have a measurable degree of retinal thinning as determined by OCT and a
      generalized reduction of sensitivity in VFT. Combining structural and functional
      findings may be used in the follow-up of patients with FRDA.

PMID- 24275984
TI  - Optic nerve sheath decompression: a surgical technique with minimal operative
      complications.
AB  - BACKGROUND: The purpose of this study was to determine the safety and efficacy of
      optic nerve sheath decompression (ONSD) with a medial transconjunctival approach
      for a variety of indications in a larger population of patients than has
      previously been reported. METHODS: A retrospective chart review was performed on
      consecutive patients who underwent ONSD between January 1992 and December 2010.
      Before ONSD, all patients had documented evidence of progressive loss of visual
      acuity or visual field, or both. Postoperative follow-up visits were scheduled at
      1 week, 1 month, and then every 3-6 months. Main outcome measures were visual
      acuity, visual fields, and surgical complications. RESULTS: Five hundred seventy
      eight eyes of 331 patients underwent ONSD for progressive vision loss due to
      various indications, which included but were not limited to idiopathic
      intracranial hypertension (IIH), progressive nonarteritic ischemic optic
      neuropathy, and optic nerve drusen (OND). During a mean follow-up of 18.7 months
      (range, 1 week to 10 years), postoperative visual acuity remained stable or
      improved in 536 of 568 eyes (94.4%) and progressively worsened in 32 of 568 eyes
      (5.6%). Visual fields remained stable or improved in 257 of 268 eyes (95.9%) and
      progressive visual field loss occurred in 11 of 268 eyes (4.1%). There were no
      reported intraoperative complications. The most common postoperative complication
      was diplopia (6.0%). CONCLUSIONS: To our knowledge, this review represents the
      largest series of patients who have undergone ONSD for any indication. Our data
      are consistent with current literature supporting ONSD as a safe and effective
      procedure for IIH. Other indications for ONSD, such as progressive visual field
      loss associated with OND, warrant further study. Regardless of the indication,
      complications following ONSD with the technique described in this report are
      infrequent.

PMID- 24275985
TI  - Massage interventions and treatment-related side effects of breast cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Massage as a complementary and alternative therapy has been
      associated with enhancing health and coping with treatment-related side effects
      in patients with breast cancer worldwide. This systematic review examined whether
      massage interventions provide any measurable benefit in breast cancer-related
      symptoms. METHODS: Randomized controlled trials (RCTs) were searched for in
      PubMed, EMBASE.com and the Cochrane Library through June 2013. We evaluated the
      quality of the studies included by the Cochrane Handbook 5.2 standards and
      analyzed the data using the Cochrane Collaboration's RevMan 5.2 software.
      RESULTS: Eighteen RCTs with a total of 950 participants were included. Compared
      with the control group, our meta-analysis showed that patients receiving regular
      use of massage had significantly greater reductions in anger and fatigue
      symptoms. However, there were no significant differences in depression, anxiety,
      pain, upper limb lymphedema, cortisol and health-related quality of life.
      CONCLUSIONS: The current evidence demonstrates that there was mild evidence that
      massage may be a useful intervention in alleviating negative emotions and fatigue
      in patients with breast cancer. More trials with longer follow-up are needed to
      determine the exact long-term efficacy of this class of complementary and
      alternative medicine on breast cancer-related symptoms and quality of life.

PMID- 24275986
TI  - Biodegradation and adsorption of C1- and C2-phenanthrenes and C1- and C2
      dibenzothiophenes in the presence of clay minerals: effect on forensic diagnostic
      ratios.
AB  - The impact of modified montmorillonites on adsorption and biodegradation of crude
      oil C1-phenanthrenes, C1-dibenzothiophenes, C2-phenanthrenes and C2
      dibenzothiophenes was investigated in aqueous clay/oil microcosm experiments with
      a hydrocarbon degrading microorganism community. Consequently, the effect on C1
      dibenzothiophenes/C1-phenanthrenes, C2-dibenzothiophenes/C2-phenanthrenes, 2+3
      methyldibenzothiophene/4-methyldibenzothiophene and 1-methyldibenzothiophene/4
      methyldibenzothiophene ratios commonly used as diagnostic ratios for oil forensic
      studies was evaluated. The clay mineral samples were treated to produce acid
      activated montmorillonite, organomontmorillonite and homoionic montmorillonite
      which were used in this study. The different clay minerals (modified and
      unmodified) showed varied degrees of biodegradation and adsorption of the C1
      phenanthrenes, C1-dibenzothiophenes, C2-phenanthrenes and C2-dibenzothiophenes.
      The study indicated that as opposed to biodegradation, adsorption has no effect
      on the diagnostic ratios. Among the diagnostic ratios reviewed, only C2
      dibenzothiophenes/C2-phenanthrenes ratio was neither affected by adsorption nor
      biodegradation making this ratio very useful in forensic studies of oil spills
      and oil-oil correlation.

PMID- 24275988
TI  - Dihydromatricariate-based triglycerides, glyceride ethers, and waxes in the
      australian soldier beetle,Chauliognathus lugubris (Coleoptera: Cantharidae).
AB  - The soldier beetleChauliognathus lugubris is shown to contain triglycerides and
      glyceride ethers of 8-dihydromatricaria acid, and waxes of the C12 homolog, of
      this acid, as well as the previously reported free acid. The triglycerides
      contain one, two, or three dihydromatricariate moieties, with any remaining
      positions esterified with normal fatty acids. The glyceride ethers were
      monostearyl ethers of glycerol esterified with dihydromatricaria acid and oleic
      or linoleic acid. The waxes, which also include a dihydromatricaria chromophore
      in the alcohol moiety, occur only in the females and are present in paired
      accessory glands in the abdomen. The ethers are restricted to females and appear
      to be associated with developing eggs. The triglycerides are much more abundant
      in females than males. Triglycerides, glyceride ethers, and waxes represent about
      95% of the dihydromatricariate moiety (average, ca. 590 MUg) in females with free
      acid the remainder; in males free acid is present to over 50% (ca. 22 MUg) and
      the remainder is triglyceride (ca. 15 MUg). Larvae contain mainly
      tridihydromatricariate-substituted triglyceride and a smaller quantity of the
      free acid. 

PMID- 24275987
TI  - Effective biodemulsifier components secreted by Bacillus mojavensis XH-1 and
      analysis of the demulsification process.
AB  - The purpose of the present study was to investigate the effective components of
      the demulsifying bacterial strain Bacillus mojavensis XH-1 and its
      demulsification process. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and the shotgun LC-MS/MS method were used to separate
      and identify proteins with efficient demulsification activity. The zeta potential
      changes of the emulsion before and after addition of the biodemulsifier were
      tested, and the relationships between oil-in-water interfacial tension, the
      demulsification efficiency and the biodemulsifier structure were examined. The
      study results indicate that the effective biodemulsifier components were
      extracellular proteins attached to the cells or secreted into the culture
      solution that presented as a 50-80 kDa band observed by SDS-PAGE. Six of the
      proteins were unknown or unnamed, and the demulsifying functions of another 14
      proteins had not been previously reported. The main demulsification mechanisms
      were determined to be solubilization and replacement. When the concentration of
      the biodemulsifier was low, the replacement mechanism dominated, and the
      demulsification ratio increased with the biodemulsifier concentration.
      Solubilization dominated when a high concentration of biodemulsifier was
      provided, and the demulsification ratio decreased as the biodemulsifier
      concentration increased.

PMID- 24275989
TI  - Beneficial arthropod behavior mediated by airborne semiochemicals. II.
      Olfactometric studies of host location by the parasitoidMicroplitis croceipes
      (Cresson) (Hymenoptera: Braconidae).
AB  - The response ofMicroplitis croceipes (Cresson) to odors from a plant-host complex
      was investigated using a four-choice olfactometer. Female, but not male,
      parasitoids responded in a dose-dependent fashion to volatiles from the plant
      host complex and oviposition experience enhanced this response. Female age had no
      apparent effect on the response. Both artificially damaged leaves and frass
      elicited positive responses but of lower magnitude than those elicited by the
      plant-host complex. Volatiles collected from the plant-host complex placed on
      filter paper also elicited positive responses by female parasitoids. 

PMID- 24275990
TI  - Iridoid glycoside sequestration by two aposematicPenstemon-feeding geometrid
      larvae.
AB  - The iridoid glycoside catalpol was found to be sequestered by larvae ofMeris
      alticola feeding onPenstemon virgatus and by larvae ofNeoterpes graefiaria which
      utilizeP. barbatus. The strikingly similar larval patterns of these two ennomine
      geometrids were previously considered to be disruptive, but predator-based
      Mullerian mimicry is equally likely to be involved. The cryptic adult moths
      generally contain only small amounts of catalpol, having left most of the bitter
      iridoid in the pupal case and in the meconium excreted after eclosion.
      OneNeoterpes female did contain considerable catalpol in the abdomen, presumably
      in the eggs. 

PMID- 24275991
TI  - Evaluation of some weed extracts against field dodder on alfalfa (Medicago
      sativa).
AB  - Experiments were conducted to evaluate the effectiveness of some weed extracts
      against field dodderCuscuta campestris Yunck. on alfalfa (Medicago stiva L.) and
      to identify and quantify the phytotoxic agents of these extracts. All
      concentrations of aqueous extract of every weed showed significant effectiveness
      on dodder when compared to the untreated plant under lath house and field
      conditions. Control percentages of the (0.5 g) of Bermuda grass (Cynodon
      dactylon) and wall goosefoot (Chenopodium murale) ranged between 83 and 96, and
      the same concentration caused injury to alfalfa foliage up to 43% when applied in
      the field. Phytotoxic agents were identified as phenolic compounds such as
      chlorogenic, isochlorogenic,p-coumaric acids, and scopoletin. Their quantities
      varied with species; Bermuda grass had the highest content (32.2 MUg/g dry
      weight) followed by Johnson grass (Sorghum halepense), well goosefoot, and tumble
      pigweed (Amaranthus albus). These results might aid in screening for effective
      alternate approaches for controlling dodder on alfalfa planted for seeds. 

PMID- 24275992
TI  - Extraction of tannin from fresh and preserved leaves.
AB  - The extractability of tannin from fresh, lyophilized, and dried leaves collected
      at various times in the growing season was determined using the radial diffusion
      assay for protein-precipitating phenolics. The amount of tannin extracted
      depended on the method of leaf preservation and on the maturity of the leaf.
      Early in the season, more tannin was extracted from lyophilized leaves than from
      fresh leaves, but late in the season more tannin was extracted from fresh leaves.
      At all times, more tannin was extracted with aqueous acetone than with aqueous or
      acidic methanol. 

PMID- 24275993
TI  - Behavioral and electrophysiological studies with live larvae and larval rinses of
      the red imported fire ant,Solenopsis invicta Buren (Hymenoptera: Formicidae).
AB  - Behavioral and electrophysiological studies with live intact larvae and larval
      rinses of the red imported fire ant,Solenopsis invicta Buren, give undeniable
      evidence of a volatile material associated with the larvae of the ant that is
      capable of eliciting a response from brood-tending workers. In a Y-tube bioassay,
      worker ants were attracted equally to an airstream blown over sibling larvae or
      heterocolonial larvae. Workers were also attracted to a rinse of the larvae in a
      spot bioassay, aggregated about a piece of surrogate brood in another bioassay,
      and retrieved surrogate brood treated with the rinse material. A dose-response
      curve constructed from electroantennograms of workers revealed a receptor
      response of 1-100 brood equivalents. 

PMID- 24275994
TI  - The influence of dietarybeta-carboline alkaloids on growth rate, food
      consumption, and food utilization of larvae ofSpodoptera exigua (Hubner).
AB  - beta-Carboline alkaloids are found worldwide in many plant families. Harman,
      harmine, and other simple beta-carboline alkaloids were tested for activity
      against a generalist phytophagous insect, the beet army worm [Spodoptera exigua
      (Hubner)]. Chronic dietary exposure tests (neonate to pupa) reveal potent
      antifeedant and possible toxic effects. Acute dietary exposure tests on fifth
      instar larvae also demonstrate antifeedant activity. 

PMID- 24275995
TI  - Sex pheromone of femaleMyelois cribrella Hubner (Lepidoptera: Pyralidae) :
      Chemical identification, electrophysiological evaluation, and field attractancy
      tests.
AB  - Females ofMyelois cribrella contain about 20 ng/gland of the primary sex
      pheromone components (Z)-9-tetradecenyl acetate, (9Z,12E)-9,12-tetradecadienyl
      acetate, and (Z)-11-hexadecenyl acetate in proportions of 4?11?5, respectively.
      These physiologically active components are accompanied by a number of related
      compounds such as (Z)-9-tetradecen-1-ol, hexadecyl acetate, (9Z,12E)-9,12
      tetradecadien-1-ol, (Z)-11-hexadecen-1-ol, octadecyl acetate, octadecan-1-ol, and
      eicosyl and docosyl acetates. Octadecyl acetate, the most abundant component,
      represents about 42 ng/female moth; however, no physiological activity could be
      attributed to it. In field tests, a trap baited with a 1-mg mixture of (Z)-9
      tetradecenyl acetate, (9Z,12E)-9,12-tetradecadienyl acetate, and (Z)-11
      hexadecenyl acetate in a ratio of 1?2?1 caught more male moths than three live
      female moths. 

PMID- 24275996
TI  - Nest plundering allomones of the fire beeTrigona (Oxytrigona) mellicolor.
AB  - Ten volatile compounds derived from the cephalic glands of the fire beeTrigona
      (Oxytrigona)mellicolor were bioassayed for possible allomonal activities
      facilitating nest plundering. Two diketones, (E)-3-heptene-2,5-dione and (E)-3
      nonene-2,5-dione, caused the honeybeeApis mellifera to display avoidance behavior
      and reduced defensive behavior. These diketones are produced in relatively large
      quantities in fire-bee cephalic glands. 

PMID- 24275997
TI  - Some communicatory functions of scent marking in the cotton-top tamarin (Saguinus
      oedipus oedipus).
AB  - The ability of cotton-top tamarins to discriminate between scents from
      conspecifics and those from other tamarin species, and between scents from
      conspecific individuals was tested. Cotton-tops scent mark with specialized skin
      glands in the circumgenital area. Females possess larger glands than males and
      show more scent-marking behavior. In the first experiment, subjects were
      presented with a glass rod scented with either material collected from the
      surface of the scent glands of a conspecific female, with scent material from a
      female of a related species, or with an unscented rod. Glass rods carrying scent
      from conspecifics were sniffed more frequently than rods carrying scent from
      related tamarin species or unscented rods. A second experiment offered a choice
      between two glass rods, one scent marked by aSaguinus o. oedipus female, the
      second one scent marked by aSaguinus fusdcollis female. Shelves carrying rods
      that had been scent marked by conspecifics were contacted more frequently than
      those carrying rods marked by heterospecific females. Scent marks from
      conspecific females were also sniffed more frequently. A third experiment
      compared the level of responses to rods carrying material collected from the
      scent glands of female individuals to which the subjects had been habituated with
      their responses to rods carrying scent from females to which they had not been
      habituated. Contacting and sniffing responses to the scents of novel females were
      higher than those to the scents of females to which the subjects had been
      habituated. 

PMID- 24275998
TI  - Tetraponerines, toxic alkaloids in the venom of the Neo-Guinean pseudomyrmecine
      antTetraponera sp.
AB  - The Neo-Guinean pseudomyrmecine ant,Tetraponera sp. utilizes its modified sting
      to smear upon enemies a contact poison with strong deterring and toxic
      properties. The venom, which originates from the poison gland, contains a mixture
      of eight closely related, alkaloids (tetraponerine-1 to -8). The structure of
      tetraponerine-8 was established by an X-ray diffraction analysis and was reported
      previously. The structure of five other members of the series has now been
      determined by comparison of their spectral properties with those of tetraponerine
      8 and of model compounds. 

PMID- 24275999
TI  - Partial inhibition of pheromone production inDendroctonus ponderosae (Coleoptera:
      Scolytidae) by polysubstrate monooxygenase inhibitors.
AB  - Female and male mountain pine beetles,Dendroctonus ponderosae Hopkins, were
      treated topically with piperonyl butoxide or sesame oil, both of which are known
      to inhibit poly substrate monooxygenase activity. Beetles then exposed to vapors
      of the host monoterpenes alpha-pinene and myrcene were found to contain reduced
      levels of the pheromonestrans-verbenol and ipsdienol, as well as a buildup of
      monoterpene precursors. Polysubstrate monooxygenase enzymes appear to be at least
      partially responsible for the detoxification of host monoterpenes and for the
      production of terpene alcohol pheromones in this species. 

PMID- 24276000
TI  - Male confusion of the nun moth with disparlure at high and low population
      densities.
AB  - The feasibility of using the synthetic sex pheromone, disparlure, as a mating
      confusant of the nun moth (Lymantria monacha L.) was investigated on wild
      populations occurring in outbreak proportions in Poland and in low density in
      Czechoslovakia. The size of experimental plots ranged from 1 to 12 hectares. The
      amounts of pheromone applied were 10 or 20 g/hectare. Three types of slow-release
      formulations of a racemic mixture of disparlure were tested: (1) a spray
      formulation with latex as a carrier, (2) a tubing of natural rubber, and (3)
      sawdust of a porous material used for making tips of fiber-tip pens. All three
      pheromone formulations prevented significant numbers (98.6-100% in the low
      density situation, 90-96.2% during the outbreak) of the males from locating a
      discrete source of pheromone (a trap containing synthetic pheromone or a female)
      during the whole flight period, indicating long-lasting efficiency of the
      formulations. 

PMID- 24276001
TI  - Chemical defense in birch. Platyphylloside: A phenol fromBetula pendula
      inhibiting digestibility.
AB  - Extracts of Scandinavian birch (Betula pendula Roth) buds and internodes of
      varying twig diameters have been investigated for their inhibitory effect on
      ruminant digestibility in vitro. The predominant inhibitory effect was observed
      in extracts containing the phenol platyphylloside, 5-hydroxy-1,7-bis-(4-hydroxy
      phenyl)-3-heptan-one-3-O-beta-D-glucopyranoside. Isolation of the pure compound
      and incubation with rumen inocula showed that digestibility was negatively
      related to the concentration. Significant effect was measured below the
      concentration naturally occurring in birch (0.8% of dry matter). Another isolated
      compound, the closely related rhododendrin, 4-(4-hydroxyphenyl)-2-butanol-2-O
      beta-D-glucopyranoside, did not depress digestibility within the concentrations
      found in birch. An important phenol of buds, apigenin-4',7-dimethylether, did not
      have any measurable effect on digestibility, while a nonphenolic fraction of bud
      extract had a slight inhibitory effect on digestibility. Implications for
      browsers feeding on birch are briefly discussed. 

PMID- 24276002
TI  - Chemical aspects of host-plant specificity in threeLarrea-feeding grasshoppers.
AB  - The host-selection behavior of three species of grasshopper feeding on creosote
      bush,Larrea tridentata, in southern California was investigated. The species
      wereBootettix argentatus, which is monophagous;Ligurotettix coquilletti,
      oligophagous; andCibolacris parviceps, polyphagous. The monophagous species is
      stimulated to bite by nordihydroguaiaretic acid (NDGA), a compound that is
      characteristic of the host plant and that may comprise up to 10% of the dry
      weight of the leaf. Host specificity ofB. argentatus is enhanced by deterrent
      responses to compounds present in the surface waxes of all non-host-plant
      species. Both the oligophagous and polyphagous species are deterred by NDGA at
      naturally occurring concentrations. Their association withLarrea is probably
      based on tolerance of the plant chemicals rather than on dependence on specific
      chemicals. Factors other than the chemistry of the plant probably also contribute
      to the specificity ofB. argentatus andL. coquilletti. 

PMID- 24276003
TI  - Gypsy moth mating disruption: Dosage effects.
AB  - Small (1-hectare) plots in a dense gypsy moth (Lymantria dispar) infestation were
      treated with 5, 50, or 500 g racemic disparlure, and effects on male trap catch
      and mating behavior were studied. Capture of males in traps baited with 1, 10,
      100, or 1000 MUg (+)-disparlure declined as disruptant dosages increased. Traps
      with high levels of attractant caught moths when capture in those with lower
      baitings was dramatically reduced. While all disruptant dosages reduced trap
      catch, it was reducd at least 95% at all attractant levels at the 500-g
      disruptant application rate. Visual estimates indicated that male moth density
      was similar in treated and control plots; female mating success was reduced 6.5,
      34.5, and 84% in plots with 5, 50, and 500 g/ hectare disruptant, respectively.
      The duration of precopulatory and copulatory periods was similar for all females
      that were observed mating, regardless of disruptant treatment. It is proposed
      that reduced trap catch and female mating success are due to effects of
      atmospheric synthetic disparlure (disruptant) camouflaging natural attractant
      point sources. 

PMID- 24276004
TI  - Ferulate esters of higher fatty alcohols and allelopathy inKalanchoe
      daigremontiana.
AB  - Ferulate esters of normal C22-C30 alcohols were found in the root extract
      ofKalanchoe daigremontiana and the freen-C30 alcohol, triacontanol, was found on
      the leaves. Ferulic acid was isolated from the vermiculite in which plants were
      grown. Whole plant and tissue culture experiments were done to investigate the
      role of ferulic acid as an allelochemical and of triacontanol as a plant growth
      regulator inK. daigremontiana and other bioassay systems. No positive growth
      responses to triacontanol were observed, but inhibitation of growth response of
      plantlets by ferulic acid was seen. 

PMID- 24276005
TI  - Sex pheromone components of the oblique-banded leafroller,Choristoneura rosaceana
      in the Okanagan Valley of British Columbia.
AB  - (Z)-11-Tetradecen-1-yl acetate, (E)-11-tetradecen-1-yl acetate, and (Z)-11
      tetradecen-1-ol were previously reported as the sex pheromone in New York strains
      of the oblique-banded leafroller,Choristoneura rosaceana (Harris), and (E)-11
      tetradecen-1-ol was tentatively identified in female tip extracts. For Okanagan
      Valley strains ofC. rosaceana, an additional component, (Z)-11-tetradecenal, was
      identified from female tip extracts by split-less capillary gas-liquid
      chromatography and mass spectroscopy and was strongly stimulatory in
      electroantennogram studies. In field tests, 3 mg of 96.5?2?1.5 (Z)-11-tetradecen
      1-yl acetate, (E)-11-tetradecen-1-yl acetate, and (Z)-11-tetradecen-1-ol
      (containing approx. 1%E isomer) was not as attractive as female-baited traps, and
      significant numbers of European leafrollerArchips rosanus L. were attracted. The
      above blend with 1% (Z)-11-tetradecenal added was significantly more attractive
      than traps baited with femaleC. rosaceana, butA. rosanus males were still
      attracted. Increased percentages of (Z)-11-tetradecenal up to 4% caused increased
      catches ofC. rosaceana and decreased catches ofA. rosanus. Low amounts of (E)-11
      tetradecen-1-ol and (E)-11-tetradecenal male also contribute to increased
      specificity of the synthetic pheromone blend toC. rosaceana. 

PMID- 24276006
TI  - Glucocapparin variability among four populations ofIsomeris arborea Nutt.
AB  - Glucocapparin (methylglucosinolate), a putative defense compound, was found to
      vary between desert and nondesert populations ofIsomeris arborea (Capparaceae):
      Plants from desert populations contained greater concentrations than nondesert
      plants in four of the five organs analyzed. Immature leaves at desert sites had
      average glucocapparin concentrations of 9.2 mg/g and 8.4 mg/g, while nondesert
      sites averaged 6.0 mg/g and 4.6 mg/g. Mature leaves from desert sites had average
      concentrations of 12.8 mg/g and 7.9 mg/g; leaves from plants at nondesert sites
      contained approximately one third to one half of those concentrations. A similar
      pattern was observed in capsule walls and seeds but not in flower buds; for
      these, non-desert plants contained a slightly higher concentration of
      glucocapparin. Our studies show that nitrogen and glucocapparin concentrations
      fluctuate throughout the year and contribute to the observed variability among
      populations during any particular season. Glucocapparin may fluctuate seasonally
      as much as 37% in immature leaves and 78% in mature leaves. In a controlled
      experiment, glucocapparin concentration varied inversely with nitrogen fertilizer
      treatment. The plants treated with fertilizer lacking nitrogen ranged from 10.1
      mg/g to 10.9 mg/g glucapparin, which was roughly twice the concentration of those
      supplied with 20 mM nitrogen in the fertilizer. 

PMID- 24276007
TI  - Attraction of adultDiabrotica (Coleoptera: Chrysomelidae) to corn silks and
      analysis of the host-finding response.
AB  - Volatile chemicals from corn silks attractedDiabrotica virgifera virgifera
      LeConte andD. barberi (Smith and Lawrence). The behavioral response of both
      species of beetles to the host plant was typified by four distinct phases:
      perception, random movement, orientation to the source, and search with
      reorientation. The perception phase was composed of stationary behaviors, while
      the random, orientation, and search phases were composed of directed and
      nondirected movements. Each of the movement phases had a characteristic response
      pattern composed of the ratio of upwind, lateral, and downwind walking and flight
      movements, which affected net displacement of the beetle in the flight tunnel.
      The perception phase occurred within and between the other phases and was
      responsible for initiating changes from one movement phase to another (based on
      the presence or absence of volatiles from corn silks). Host finding was flexible,
      and the response pattern fit a flow-chart type of response, rather than a single
      stereotyped sequence of behaviors. 

PMID- 24276008
TI  - Trail-following behavior ofReticulitermes hesperus Banks (Isoptera:
      Rhinotermitidae).
AB  - The behavior ofReticulitermes hesperus Banks pseudergates (workers) was assessed
      on artificial trails containing different concentrations of sternal gland
      extract. On nongiadient trails, more pseudergates were recruited to trails of
      greater pheromone concentration, they traveled a greater distance without
      pausing, and their rate of locomotion increased over that observed on trails of
      lesser concentration (positive orthokinesis). Of the individuals pausing before
      completing trails of high concentration, fewer left the trails or reversed
      direction (negative klinokinesis) than on trails of lower concentration. Termites
      walking down concentration gradients failed to complete these trails to the low
      concentration termini. At a point representing an average decrease of slightly
      more than 10-fold in the original concentration of pheromone, individuals
      reversed their direction of travel and returned to the high-concentration
      terminus. Termites walking up pheromone gradients proceeded to the high
      concentration termini without reversing direction.R. hesperus pseudergates are
      thus able to orient along a gradient of trail pheromone by longitudinal
      klinotaxis. 

PMID- 24276009
TI  - The role of leaf lipids in food selection by larvae of the tobacco
      hornworm,Manduca sexta.
AB  - The role of leaf lipids in food plant selection by larvae ofManduca sexta was
      investigated by measuring preference responses in a two-choice preference test
      using glass fiber filter paper disks laced with extract (test) or water
      (control). The larvae respond to the petroleum ether extract of whole leaves of
      the host-plantLycopersicon esculentum (tomato) extract in a concentration
      dependent manner. At "natural concentration" it is the most strongly stimulating
      extract or compound yet tested using the disk test. This response is affected by
      food plant experience of the larvae, suggesting stimulation by plant-specific
      compounds in the extract. The extract contains volatile compounds that attract
      the larvae. In contrast, it does not promote continued feeding on an agar
      cellulose diet that incorporates the extract. Also stimulating are the extracts
      of leaf surfaces of two hosts,L. esculentum andSolanum pseudocapsicum, and two
      acceptable nonhosts,Brassicae napus andVigna sinensis, indicating the presence of
      nonpolar feeding stimulants at the leaf surface. However, similar leaf-surface
      extracts of the unacceptable plantCanna generalis were inactive, although the
      surface extraction process renders this plant acceptable. Leaf-surface extracts
      ofL. esculentum, S. pseudocapsicum, andB. napus evoke feeding responses that are
      qualitatively comparable to those of their corresponding leaves. However, no such
      parallel is found for surface extracts ofV. sinensis andC. generalis. Thus,
      nonpolar compounds at the leaf surface of host and some acceptable non-host-plant
      species strongly stimulate feeding and hence must play an important role in food
      selection by the tobacco hornworm. 

PMID- 24276010
TI  - Identification of sex pheromone components ofSpodoptera sunia Guenee
      (Lepidoptera: Noctuidae).
AB  - Moths belonging to the speciesSpodoptera sunia have been recognized as a new pest
      of cotton in Central America. By means of electro-physiologic investigations,
      solid sample injection gas chromatography, and combined gas chromatography-mass
      spectrometry, (Z)-9-tetradecenyl acetate, (9Z,12E)-9,12-tetradecadienyl acetate,
      (Z)-9-tetradecen-1-ol, and (Z)-11-hexadecenyl acetate, in a ratio of 100?5?31?20,
      were identified in the pheromone gland of female insects. These substances should
      serve as a base for the development of a pheromone-monitoring system for this
      lepidopteran pest. 

PMID- 24276011
TI  - Lectin studies of surface carbohydrates and induction of gland secretion in the
      free-living stages ofSchistosoma mansoni.
AB  - Secretion from glands was observed when cercariae ofSchistosoma mansoni were
      exposed to certain lectins. Lectins fromMaclura pomifera, Pisum sativum,
      andTriticum vulgaris, were effective at 7.5 MU/ml. The effects of cercarial gland
      secretion caused byT. vulgaris agglutinin andArachis hypogaea agglutinin were
      blocked by pretreatment with the inhibiting glycan. Discharge of glands was not
      visualized after exposure of miracidia to lectins. The distribution of five
      labeled lectins was determined on live miracidia and cercariae. OnlyT. vulgaris
      agglutinin generally labeled the cercarial and miracidial bodies. Specific
      labeling occurred with the other lectins on the anterior, in glands or on their
      secretions, in flame cells in both stages, and on an unidentified ring of cells
      in miracidia. The possible mechanisms involved in changes caused by the lectins
      are discussed. 

PMID- 24276012
TI  - Coyote estrous urine volatiles.
AB  - Samples of female coyote urine were taken once or twice each week during the
      winter and spring for two years. Headspace analysis was employed with Tenax GC
      trapping and GC-MS. Tenax trapping was started in less than 1 hr after sampling,
      and mild conditions were used to minimize losses of highly volatile and labile
      compounds. Thirty-four compounds were identified. They include sulfur compounds,
      aldehydes and ketones, hydrocarbons, and one alcohol. The principal constituent
      is methyl 3-methylbut-3-enyl sulfide, which usually comprised 50% or more of the
      total volatiles observed. The concentration of many constituents varied widely.
      This appeared to be quasiperiodic for five of the constituents, with a period of
      a few weeks, and with pronounced maxima at the peak of estrus. Apparently these
      compounds are 3-methyltetrahydrothiophene, methyl 3-methylbutyl sulfide, octanal,
      dodecanal, and bis(3-methylbut-3-enyl) disulfide. One or more of these compounds
      may have pheromonal activity in coyote relationships. 

PMID- 24276013
TI  - Defensive odor emission from larvae of two sawfly species,Pristiphora erichsonii
      andP. wesmaeli.
AB  - The emission of species-specific odors byPristiphora erichsonii andP. wesmaeli is
      accompanied by a characteristic defensive behavior called "snap bending." When
      the larvae are disturbed, blends of volatile compounds are emitted from ventral
      glands. The odor ofP. erichsonii, a colonial species, is composed of bornyl
      acetate, borneol,trans-pinocarveol, myrtenol, benzaldehyde, and tetradecyl,
      hexadecyl, and octadecyl acetates, whereas that of the solitaryP. wesmaeli is
      composed of 3-carene-10-al, linalool, myrtenal, and benzaldehyde. The role of
      these compounds in the defensive behavior of the larvae is discussed. 

PMID- 24276014
TI  - What is chemical ecology?

PMID- 24276015
TI  - Combining temperature and force to study folding of an RNA hairpin.
AB  - RNA folding in cells typically occurs at mesophilic temperatures. However, in
      vitro, RNA can be unfolded either by increasing temperature to values that are
      much higher than physiological, or by mechanically pulling structures apart at
      ambient temperature. To directly study RNA folding at physiological temperatures
      and to unify thermodynamics measured by melting and pulling, we developed
      temperature-controlled optical tweezers (thermal tweezers) that can be used to
      mechanically unfold single RNA molecules at mesophilic temperatures. Folding of a
      20-base-pair tetraloop hairpin was studied under different ionic conditions and
      at temperatures ranging from 22  degrees C to 42  degrees C. At each temperature,
      single hairpin molecules were held at constant force, and their two-state folding
      equilibria were monitored. The change in free energy derived from these
      measurements was used to construct a phase diagram of RNA structure using force
      and temperature as variables. Furthermore, we derived DeltaG(0pN,T), the folding
      free energy at zero force and temperature T, by subtracting the stretching energy
      of unfolded RNA from the reversible mechanical work done to unfold the hairpin.
      DeltaG(0pN,T) and its salt dependence agree reasonably well with the predictions
      by the nearest neighbor model. Under each ionic condition, DeltaG(0pN,T) depended
      linearly on temperature, yielding DeltaH(exp) and DeltaS(exp) that also matched
      the predictions. The combination of force and temperature to study RNA folding is
      a step toward unifying thermodynamics measured by thermal melting and mechanical
      unfolding, and opens a new path for directly monitoring temperature induced RNA
      structural changes, as it occurs often in biology.

PMID- 24276016
TI  - Inverse correlation of serum inflammatory markers with metabolic parameters in
      healthy, Black and White prepubertal youth.
AB  - OBJECTIVE: To examine for the first time the associations between pro
      inflammatory cytokines and obesity-related metabolic biomarkers in, exclusively
      prepubertal, otherwise healthy obese and non-obese Black and White children, 7-9
      years of age. DESIGN AND METHODS: Body mass index (BMI), homeostasis model
      assessment-estimated insulin resistance, visceral adipose tissue and subcutaneous
      adipose tissue (SAT (magnetic resonance imaging)); total body fat (dual-energy X
      ray absorptiometry), ectopic, intrahepatic lipid (IHL) and intramyocellular lipid
      (IMCL) fat (proton magnetic resonance spectroscopy) and serum levels of
      interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and
      monocyte chemoattractant protein-1 were measured in 40 obese and non-obese
      children. Relationships between inflammatory cytokines and obesity were assessed
      by analysis of variance and Spearman's rank correlation. RESULTS: Significant
      inverse correlations were found between BMI z-score, SAT, total BF, and IHL and
      levels of TNF-alpha (Spearman's rho=-0.36, -0.39, -0.43 and -0.39, respectively;
      P<0.05). Levels of IL-8 were significantly and inversely correlated with IMCL (
      0.39; P=0.03) and remained significant after adjusting for race. IMCL was
      inversely associated with TNF-alpha only after adjusting for race (-0.37;
      P=0.04). CONCLUSIONS: Relationships between pro-inflammatory and metabolic
      markers commonly observed in adults are reversed in healthy, Black and White
      children before puberty. Prospective studies are warranted to determine how these
      inverse relationships modify chronic disease risk later in life.

PMID- 24276017
TI  - Brain-derived neurotrophic factor in human subjects with function-altering
      melanocortin-4 receptor variants.
AB  - BACKGROUND: In rodents, hypothalamic brain-derived neurotrophic factor (BDNF)
      expression appears to be regulated by melanocortin-4 receptor (MC4R) activity.
      The impact of MC4R genetic variation on circulating BDNF in humans is unknown.
      OBJECTIVE: The objective of this study is to compare BDNF concentrations of
      subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants
      with those of controls with common sequence MC4R. METHODS: Circulating BDNF was
      measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian
      heritage ((mean+/-s.d.): age, 15.7+/-6.5 years; body mass index z-scores (BMI-Z),
      1.63+/-1.03) and 69 subjects of Hispanic heritage (10.8+/-3.6 years; BMI-Z,
      1.57+/-1.07). MC4R variants were characterized in vitro by cell surface
      expression, receptor binding and cyclic AMP response after agonist
      administration. BDNF single-nucleotide polymorphisms (SNPs) rs12291186, rs6265
      and rs7124442 were also genotyped. RESULTS: In the Pima cohort, no significant
      differences in serum BDNF was observed for 43 LOF subjects versus 65 LOF-matched
      controls (age, sex and BMI matched; P=0.29) or 20 GOF subjects versus 20 GOF
      matched controls (P=0.40). Serum BDNF was significantly associated with genotype
      for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99);
      BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the
      Hispanic cohort, plasma BDNF was not significantly different among 21 LOF
      subjects, 20 GOF subjects and 28 controls (P=0.79); plasma BDNF was not predicted
      by BDNF genotype or BDNF-x-MC4R genotype interaction. CONCLUSIONS: Circulating
      BDNF concentrations were not significantly associated with MC4R functional
      status, suggesting that peripheral BDNF does not directly reflect hypothalamic
      BDNF secretion and/or that MC4R signaling is not a significant regulator of the
      bulk of BDNF expression in humans.

PMID- 24276019
TI  - APOE genotype and brain development.

PMID- 24276018
TI  - Both GLS silencing and GLS2 overexpression synergize with oxidative stress
      against proliferation of glioma cells.
AB  - Mitochondrial glutaminase (GA) plays an essential role in cancer cell metabolism,
      contributing to biosynthesis, bioenergetics, and redox balance. Humans contain
      several GA isozymes encoded by the GLS and GLS2 genes, but the specific roles of
      each in cancer metabolism are still unclear. In this study, glioma SFxL and LN229
      cells with silenced isoenzyme glutaminase KGA (encoded by GLS) showed lower
      survival ratios and a reduced GSH-dependent antioxidant capacity. These GLS
      silenced cells also demonstrated induction of apoptosis indicated by enhanced
      annexin V binding capacity and caspase 3 activity. GLS silencing was associated
      with decreased mitochondrial membrane potential (DeltaPsim) (JC-1 dye test),
      indicating that apoptosis was mediated by mitochondrial dysfunction. Similar
      observations were made in T98 glioma cells overexpressing glutaminase isoenzyme
      GAB, encoded by GLS2, though some characteristics (GSH/GSSG ratio) were different
      in the differently treated cell lines. Thus, control of GA isoenzyme expression
      may prove to be a key tool to alter both metabolic and oxidative stress in cancer
      therapy. Interestingly, reactive oxygen species (ROS) generation by treatment
      with oxidizing agents: arsenic trioxide or hydrogen peroxide, synergizes with
      either KGA silencing or GAB overexpression to suppress malignant properties of
      glioma cells, including the reduction of cellular motility. Of note, negative
      modulation of GLS isoforms or GAB overexpression evoked lower c-myc and bcl-2
      expression, as well as higher pro-apoptotic bid expression. Combination of
      modulation of GA expression and treatment with oxidizing agents may become a
      therapeutic strategy for intractable cancers and provides a multi-angle
      evaluation system for anti-glioma pre-clinical investigations. KEY MESSAGE:
      Silencing GLS or overexpressing GLS2 induces growth inhibition in glioma cell
      lines. Inhibition is synergistically enhanced after arsenic trioxide (ATO) or
      H2O2 treatment. Glutatione levels decrease in GLS-silenced cells but augment if
      GLS2 is overexpressed. ROS synergistically inhibit cell migration by GLS
      silencing or GLS2 overexpression. c-myc, bid, and bcl-2 mediate apoptosis
      resulting from GLS silencing or GLS2 overexpression.

PMID- 24276020
TI  - RNAi Therapeutics in Autoimmune Disease.
AB  - Since the discovery of RNA interference (RNAi), excitement has grown over its
      potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to
      change biological processes post-transcriptionally in various health conditions
      such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA
      enhances stability and specificity of RNAi-based approaches whereas it has to
      reduce or prevent undesirable immune responses or off-target effects. Recent
      advances in understanding pathogenesis of autoimmune diseases have allowed
      application of these tools in vitro as well as in vivo with some degree of
      success. Further research on the design and delivery of effectors of RNAi pathway
      and underlying molecular basis of RNAi would warrant practical use of RNAi-based
      therapeutics in human applications. This review will focus on the approaches used
      for current therapeutics and their applications in autoimmune diseases, including
      rheumatoid arthritis and Sjogren's syndrome. 

PMID- 24276021
TI  - Cell penetration properties of a highly efficient mini maurocalcine Peptide.
AB  - Maurocalcine is a highly potent cell-penetrating peptide isolated from the
      Tunisian scorpion Maurus palmatus. Many cell-penetrating peptide analogues have
      been derived from the full-length maurocalcine by internal cysteine substitutions
      and sequence truncation. Herein we have further characterized the cell
      penetrating properties of one such peptide, MCaUF1-9, whose sequence matches that
      of the hydrophobic face of maurocalcine. This peptide shows very favorable cell
      penetration efficacy compared to Tat, penetratin or polyarginine. The peptide
      appears so specialized in cell penetration that it seems hard to improve by site
      directed mutagenesis. A comparative analysis of the efficacies of similar
      peptides isolated from other toxin members of the same family leads to the
      identification of hadrucalcin's hydrophobic face as an even better CPP.
      Protonation of the histidine residue at position 6 renders the cell penetration
      of MCaUF1-9 pH-sensitive. Greater cell penetration at acidic pH suggests that
      MCaUF1-9 can be used to specifically target cancer cells in vivo where tumor
      masses grow in more acidic environments. 

PMID- 24276022
TI  - A review of therapeutic aptamer conjugates with emphasis on new approaches.
AB  - The potential to emulate or enhance antibodies with nucleic acid aptamers while
      lowering costs has prompted development of new aptamer-protein, siRNA, drug, and
      nanoparticle conjugates. Specific focal points of this review discuss DNA
      aptamers covalently bound at their 3' ends to various proteins for enhanced
      stability and greater pharmacokinetic lifetimes in vivo. The proteins can include
      Fc tails of IgG for opsonization, and the first component of complement (C1q) to
      trigger complement-mediated lysis of antibiotic-resistant Gram negative bacteria,
      cancer cells and possibly some parasites during vulnerable stages. In addition,
      the 3' protein adduct may be a biotoxin, enzyme, or may simply be human serum
      albumin (HSA) or a drug known to bind HSA, thereby retarding kidney and other
      organ clearance and inhibiting serum exonucleases. In this review, the author
      summarizes existing therapeutic aptamer conjugate categories and describes his
      patented concept for PCR-based amplification of double-stranded aptamers followed
      by covalent attachment of proteins or other agents to the chemically vulnerable
      overhanging 3' adenine added by Taq polymerase. PCR amplification of aptamers
      could dramatically lower the current $2,000/gram cost of parallel chemical
      oligonucleotide synthesis, thereby enabling mass production of aptamer-3'-protein
      or drug conjugates to better compete against expensive humanized monoclonal
      antibodies. 

PMID- 24276024
TI  - Characterization of N-Linked Glycosylation in a Monoclonal Antibody Produced in
      NS0 Cells Using Capillary Electrophoresis with Laser-Induced Fluorescence
      Detection.
AB  - The N-linked glycosylation in recombinant monoclonal antibodies (mAb) occurs at
      Asn297 on the Fc region in the CH2 domain. Glycosylation heterogeneities have
      been well documented to affect biological activities such as antibody-dependent
      cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through
      their interaction with Fc-receptors. Hence, it is critical to monitor and
      characterize the N-linked glycosylation profile in a therapeutic protein such as
      a mAb for product consistency. In one approach, the glycans are first released
      from the mAb using an enzyme specific digestion, such as Protein N-Glycosidase F
      (PNGase) and subsequently they are labeled using a fluorophore, for example, 8
      aminopyrene-1,3,6-trisulfonic acid (APTS) . Here we have applied this approach
      and used Capillary Electrophoresis with Laser-Induced Fluorescence detection (CE
      LIF) to analyze a recombinant mAb produced in murine myeloma (NS0) cells. The
      technique provides short analysis times, efficient separations, and high
      sensitivity. CE-LIF peak identification was done by a combination of glycan
      standards and treatment with various exoglycosidases. Furthermore, the APTS
      labeled glycans were also analyzed using hydrophilic interaction chromatography
      (HILIC) high performance liquid chromatography (HPLC) to aid identification of
      minor peaks by sample collection and off-line mass spectrometry (MS) analysis. 

PMID- 24276023
TI  - Inactivation of caliciviruses.
AB  - The Caliciviridae family of viruses contains clinically important human and
      animal pathogens, as well as vesivirus 2117, a known contaminant of
      biopharmaceutical manufacturing processes employing Chinese hamster cells. An
      extensive literature exists for inactivation of various animal caliciviruses,
      especially feline calicivirus and murine norovirus. The caliciviruses are
      susceptible to wet heat inactivation at temperatures in excess of 60  degrees C
      with contact times of 30 min or greater, to UV-C inactivation at fluence >=30
      mJ/cm2, to high pressure processing >200 MPa for >5 min at 4  degrees C, and to
      certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.;
      noroviruses) display resistance to inactivation by low pH, while the non-enteric
      species (e.g.; feline calicivirus) are much more susceptible. The caliciviruses
      are inactivated by a variety of chemicals, including alcohols, oxidizing agents,
      aldehydes, and beta-propiolactone. As with inactivation of viruses in general,
      inactivation of caliciviruses by the various approaches may be matrix-,
      temperature-, and/or contact time-dependent. The susceptibilities of the
      caliciviruses to the various physical and chemical inactivation approaches are
      generally similar to those displayed by other small, non-enveloped viruses, with
      the exception that the parvoviruses and circoviruses may require higher
      temperatures for inactivation, while these families appear to be more susceptible
      to UV-C inactivation than are the caliciviruses. 

PMID- 24276025
TI  - Metastatic melanoma of unknown primary resembles the genotype of cutaneous
      melanomas.
AB  - BACKGROUND: Although 90% of all melanomas are of cutaneous origin, some patients
      present with melanoma metastases of unknown origin (MUP). Commonly, in these
      patients an extensive search for the primary tumor is carried out. In the past,
      genetic analyses have shown substantial differences in pathogenetic mutations
      among cutaneous, acral and mucosal melanomas. The aim of this study was to assess
      the mutational status of MUP in order to better characterize the putative origin
      of the primary tumor and to evaluate potential prognostic factors. PATIENTS AND
      METHODS: The medical records of 44 patients with MUP were analyzed and a survival
      analysis was conducted. In total, 66 paraffin samples of 44 patients were
      analyzed, and in 15 patients multiple metastases were tested. Mutational analysis
      of the BRAF, NRAS and KIT genes was carried out. RESULTS: Twenty-three patients
      (52.3%) had a mutation in the BRAF gene and 12 patients (23.8%) had a mutation in
      the NRAS gene. There were neither mutations in the KIT gene. In patients with
      multiple samples, there was 100% consistency regarding mutational status among
      the different metastases. The median overall survival (OS) was 86.4 months (39
      134). The American Joint Committee on Cancer stage at first diagnosis of
      metastatic melanoma (stage III versus IV) was significantly associated with OS (P
      < 0.001), BRAF or NRAS mutation status had no significant prognostic impact on
      clinical outcomes. CONCLUSIONS: MUP resembles the genotype of cutaneous melanoma
      and not that of mucosal melanomas.

PMID- 24276026
TI  - Metastatic breast cancer: are we treating the same patients as in the past?
AB  - BACKGROUND: Early detection and improved (neo)-adjuvant treatment has extended
      survival of breast cancer over the last decades. It remains controversial whether
      a survival benefit is achieved once metastases have occurred. This study
      investigates survival trends in metastatic breast cancer (MBC) looking at the
      distribution of prognostic factors and the time period of the diagnosis of the
      primary and metastatic disease. PATIENTS AND METHODS: In this retrospective
      study, 1635 patients, diagnosed with MBC and treated at three German cancer
      centers, were included. For the survival analysis, patients were grouped into
      three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were
      chosen according to the availability of new antineoplastic drugs for the
      treatment of MBC. Additionally, patients were divided into three risk groups
      using the simultaneously published prognostic score. RESULTS: The analysis of
      overall survival according to the date of primary diagnosis demonstrated a
      significant decline compared with the reference (a): (a versus b) hazard ratio
      (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time
      of first occurrence of metastasis, survival remains unchanged over the three
      periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435.
      However, a significant shift towards more unfavorable risk factors was seen.
      CONCLUSIONS: Although survival in MBC remains unchanged over time, patients
      developing metastatic disease have a more aggressive disease that is presumably
      compensated by more effective treatment. This alteration of tumor biology in MBC
      may be explained by a negative selection of patients with adverse risk profiles
      due to the advantages of the adjuvant therapy.

PMID- 24276027
TI  - A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy
      for metastatic non-seminomatous germ cell tumor.
AB  - BACKGROUND: Approximately a quarter of men with metastatic non-seminomatous germ
      cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after
      chemotherapy. The management of small residual masses (<=1 cm) is controversial,
      with good outcomes seen with either post-chemotherapy retroperitoneal lymph node
      dissection (PC-RPLND) or surveillance. We sought to review our experience of
      surveillance and synthesize the cumulative findings with the current literature
      in the form of a meta-analysis. PATIENTS AND METHODS: We searched PubMed, EMBASE
      and abstracts from ASCO and AUA to identify relevant, English-language studies
      for the meta-analysis. The DFCI (Dana Farber Cancer Institute) database was
      constructed from a database of men undergoing cisplatin-based chemotherapy for
      metastatic NSGCT. The outcomes of interest were the proportion with necrosis,
      teratoma or active cancer on histology at PC-RPLND (literature) and the total
      number of relapses, RP-only relapses and overall survival in men undergoing
      surveillance (literature and DFCI cohort). RESULTS: Three of 47 men undergoing
      post-chemotherapy surveillance at our institution relapsed over a median follow
      up of 5.4 years. All three were alive at a median of 4.2 years after relapse. On
      meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in
      the 588 men who underwent PC-RPLND were 71, 24 and 4%, respectively. Of the
      combined 455 men who underwent surveillance, the pooled estimate of the relapse
      rate was 5%, with an RP-only relapse rate of 3%. Of the 15 men who suffered an RP
      only relapse on surveillance, two died of disease. CONCLUSION: Surveillance is a
      reasonable strategy for men with minimal residual RP disease after chemotherapy
      and avoids an RPLND in ~97% of men who are cured with chemotherapy alone.

PMID- 24276030
TI  - Role of red cell distribution width in screening for Hb E trait in population
      screening for hemoglobin disorders.
AB  - The national screening policy for hemoglobinopathies uses the cutoffs for red
      cell indices mean corpuscular volume >80 and mean corpuscular hemoglobin >27, a
      strategy known to miss some individuals with Hb E trait (EBT), the most common
      abnormal hemoglobin in Sri Lanka. We wanted to determine if red cell distribution
      width (RDW) cutoff values would help in increasing the sensitivity of screening
      for Hb E trait. High-performance liquid chromatography was carried out as the
      gold standard to detect hemoglobinopathies and red blood cell parameters with
      colter counter. Receiver operating characteristic curve was drawn to determine
      the cutoff value for EBT against beta-trait (BTT) and other anemias. Of the 504
      patients, 246 had BTT, 110 had EBT, and 151 had other types of anemias. Mean (SD)
      RDW among patients with BTT was 16 (2.8), with EBT 14.5 (2.9), and with other
      anemias 15.8 (4.2) (P>0.001). With 14.45 as the cutoff for RDW and considering
      accepted values for mean corpuscular volume >80 and mean corpuscular hemoglobin
      >27, it gave a predictive sensitivity of 98.2% for EBT. By using RDW cutoff at
      14.45 in addition to the accepted screening indices, sensitivity of Hb E trait
      detection went up to 98.2% from 86.6%. This study highlights the importance of
      taking RDW into consideration for screening. 

PMID- 24276028
TI  - Coffee consumption and risk of nonaggressive, aggressive and fatal prostate
      cancer--a dose-response meta-analysis.
AB  - BACKGROUND: Existing epidemiological evidence is controversial regarding the
      possible associations between coffee consumption and risk of prostate cancer
      (PCa) by aggressiveness of the disease. MATERIALS AND METHODS: We conducted a
      random-effects dose-response meta-analysis to assess the relationships between
      coffee consumption and nonaggressive, aggressive and fatal PCa risk. Studies were
      identified by a search of Medline and Embase databases to 15 July 2013. We
      carried out separate analyses by grade (Gleason score: low-grade, high-grade) and
      stage (TNM staging system: localized, advanced) of the tumors. Nonaggressive
      tumors were defined as low-grade or localized, while aggressive tumors were
      defined as high-grade or advanced. RESULTS: Eight studies (three case-control and
      five cohort) were included in this meta-analysis. Gleason 7 tumors were
      classified as high-grade in one study, while in another study, Gleason 7(4 + 3)
      tumors were classified as high-grade and Gleason 7(3 + 4) as low-grade. In the
      remaining four studies, Gleason 7 tumors were excluded from the analyses or
      analyzed separately. The pooled relative risk (RR) for a consumption increment of
      3 cups/day was 0.97 [95% confidence interval (CI) 0.92-1.03] for low-grade PCa (n
      = 6), 0.97 (95% CI 0.94-0.99) for localized PCa (n = 6), 0.89 (95% CI 0.78-1.00)
      for high-grade PCa (n = 6), 0.95 (95% CI 0.85-1.06) for advanced PCa (n = 6) and
      0.89 (95% CI 0.82-0.97) for fatal PCa (n = 4). No evidence of publication bias
      was observed. Heterogeneity was absent or marginal (I(2) range = 0-26%), with the
      only exception of the analysis on advanced PCa, where moderate heterogeneity was
      observed (I(2) = 60%). When restricting the analyses only to those studies that
      defined high-grade tumors as Gleason 8-10, the inverse association became
      slightly stronger [RR: 0.84 (95% CI 0.72-0.98); n = 4]. CONCLUSIONS: Results from
      this dose-response meta-analysis suggest that coffee consumption may be inversely
      associated with the risk of fatal PCa. No clear evidence of an association with
      PCa incidence was observed.

PMID- 24276029
TI  - A rapid genetic counselling and testing in newly diagnosed breast cancer is
      associated with high rate of risk-reducing mastectomy in BRCA1/2-positive Italian
      women.
AB  - BACKGROUND: Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in
      BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this
      procedure is reluctant. PATIENTS AND METHODS: This is an observational study with
      retrospective design, using quantitative and qualitative research methods, aimed
      at evaluating the attitude towards RRM by rapid genetic counselling and testing
      (RGCT), at the time of BC diagnosis, compared with traditional genetic
      counselling and testing (TGCT), after previous BC surgery. Secondary aims were to
      investigate patient satisfaction after RRM and the rate of occult tumour in
      healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT,
      whereas 110 underwent RGCT. RESULTS: In TGCT, among 1058 patients, 209 (19.7%)
      mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209).
      Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15
      (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall
      good satisfaction, measured by interpretative phenomenological analysis 12 months
      after the intervention. CONCLUSIONS: Our study shows that RGCT in patients with a
      hereditary profile is associated with a high rate of RRM at the BC surgery time,
      this being the pathway offered within a multidisciplinary organization.

PMID- 24276031
TI  - Methylenetetrahydrofolate reductase and glutathione S-tranferase gene
      polymorphisms in secondary mixed phenotype acute leukemia: a case report.
AB  - BACKGROUND: Therapy-induced leukemia is a well-known clinical syndrome occurring
      as a late complication in patients treated with cytotoxic therapy. OBSERVATION:
      We herein present results of analysis of common gene polymorphisms in
      methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST)
      genes in a 10-year-old boy who developed very rare type of cancer, mixed
      phenotype acute leukemia, 6 years after treatment of acute lymphoblastic
      leukemia. CONCLUSIONS: Impairment in function of GST and MTHFR enzymes found in
      our patient may have contributed to the development of secondary mixed phenotype
      acute leukemia, although precise mechanism remains elusive.

PMID- 24276032
TI  - HbSD-Punjab: clinical and hematological profile of a rare hemoglobinopathy.
AB  - PURPOSE: Compound heterozygous HbSD-Punjab is an uncommon hemoglobinopathy
      encountered in Indians. Limited literature is available about its clinical
      course. The aim of this study was to describe the clinical and hematological
      profile of HbSD-Punjab patients from North India. MATERIALS AND METHODS: HbSD
      Punjab patients diagnosed in the hematology clinics between year 2000 and 2010
      were reviewed retrospectively. The diagnosis was established using high
      performance liquid chromatography, molecular analysis, and family screening.
      Clinical details, laboratory parameters, and therapy details were recorded from
      case records. RESULTS: Ten patients were identified. Median age at onset of
      symptoms was 3.5 years (interquartile range [IQR], 1.9 to 7.2). Clinical
      presentation included: anemia in 3, painful vaso-occlusive crisis in 2, acute
      chest syndrome in 2, and 3 were diagnosed incidentally. All had moderate to
      severe anemia (mean hemoglobin [Hb]: 6.8 +/- 1.2 g/dL). Eight required red cell
      transfusions (median: 3 [IQR, 2 to 8]). On high-performance liquid
      chromatography, median HbF, HbD, and HbS were 12.1% (IQR, 9 to 18.3), 39.7% (IQR,
      35 to 42), and 38.5% (IQR, 29 to 43). Five patients received hydroxyurea (HDU),
      median dose: 20 mg/kg/d (IQR, 18 to 23) with median duration of 7 months (IQR; 6,
      45). Increment in Hb and reduction in painful crisis was observed in response to
      HDU. CONCLUSIONS: HbSD-Punjab has a heterogeneous clinical presentation. Anemia
      and sickle crises are quite common. HDU may be considered for those presenting
      with severe phenotype.

PMID- 24276033
TI  - Intensive care unit admission in children with malignant or nonmalignant disease:
      incidence, outcome, and prognostic factors: a single-center experience.
AB  - OBJECTIVE: To investigate pediatric intensive care unit (PICU) admission in
      children with malignant and nonmalignant diseases who developed life-threatening
      complications. PATIENTS AND METHODS: Between 1999 and 2010, of the 1278 eligible
      pediatric patients treated for a malignant or nonmalignant disease, 54 were
      admitted to the PICU for respiratory distress (40.7%), neurological events
      (33.3%), severe sepsis (14.8%), and organ failure (11.2%). RESULTS: Rate of PICU
      admission was 4.2%, with a 2-year cumulative incidence of 4.5%. Risk factors
      associated with higher cumulative incidence of PICU admission were older age at
      study entry (P=0.003), nonmalignant underlying disease (P=0.015), and
      hematopoietic stem cell transplantation (P<0.001). Patients with
      leukemia/lymphoma were more likely to be admitted to the PICU compared with
      patients with solid tumors (P<0.001). Patients admitted because of organ failure
      had the highest frequency of death within 90 days. Factors significantly
      associated with survival at 90 days from PICU admission included: no mechanical
      ventilation (P<0.001), nonmalignant underlying disease (P=0.030), and year of
      PICU admission after 2005 (P=0.038). CONCLUSIONS: Nonmalignant disease and use of
      alternative hematopoietic stem cell transplantation were associated with higher
      risk of PICU admission. Close cooperation between hematologists and intensivists
      and definition of criteria for PICU admission and discharge contributed to
      increase in survival of these patients.

PMID- 24276034
TI  - Severe vitamin D deficiency in a patient with sickle cell disease: a case study
      with literature review.
AB  - PURPOSE: Vitamin D is essential for the normal absorption of calcium and to
      maintain calcium homeostasis. Vitamin D deficiency results in rickets,
      osteomalacia, and bony changes in the spine. Sickle cell disease patients are at
      an increased risk of vitamin D deficiency. CASE PRESENTATION: We describe a case
      of severe vitamin D deficiency and response to vitamin D supplementation in a
      patient with sickle cell disease. CONCLUSIONS: Currently, there are no
      recommendations for calcium and vitamin D supplementation in sickle cell
      patients. Vitamin D deficiency in these patients may be due to poor absorption.

PMID- 24276035
TI  - Successful treatment of recurrent metastatic nasopharyngeal carcinoma with
      oxaliplatin and doxorubicin.
AB  - Nasopharyngeal carcinoma (NPC) is a rare tumor in children and often presents as
      advanced-stage disease. NPC in children is treated with neoadjuvant chemotherapy
      and radiotherapy. The prognosis for children who relapse after treatment is
      extremely poor. This report describes the successful treatment and long-term
      disease-free survival of a 16-year-old male patient with a history of stage IVA
      NPC, who recurred with pulmonary and hepatic metastases. The patient was treated
      with a novel combination of oxaliplatin and doxorubicin without irradiation. 

PMID- 24276036
TI  - Chronic fatigue in long-term survivors of childhood lymphomas and leukemia:
      persistence and associated clinical factors.
AB  - BACKGROUND: Chronic fatigue (CF) is an important late effect after childhood
      malignancies. Our aim was to assess CF persistence over time, concurrent
      comorbidities, and associations with clinical symptoms. PROCEDURE: A total of 102
      long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53
      and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated
      for CF at a second TP after a median interval of 2.7 years. At TP2 a survey,
      including self-reported and objectively measured variables, assessed depressive
      symptoms, pain, and physical activity. RESULTS: A total of 32 of the 53 reported
      CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had
      changed their fatigue status between first and second assessment (converters).
      Major somatic comorbidities were equally distributed among the groups. After
      exclusion of converters and survivors with major comorbidity/pregnancy, 27
      persistent CF (PCF) cases and 35 controls were compared. PCF cases reported
      significantly more depression, sleeping problems, anxiety, pain, and reduced
      physical function. Further, they were less physically active than controls
      (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms
      remained the only significant predictor of PCF. CONCLUSIONS: Long-term survivors
      of childhood cancer with PCF are characterized by more depressive symptoms,
      anxiety, pain, insomnia, and less physical activity.

PMID- 24276037
TI  - Clinical features and treatment outcomes of Langerhans cell histiocytosis: a
      nationwide survey from Korea histiocytosis working party.
AB  - A nationwide survey was conducted to clarify the clinical features and outcomes
      of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis
      Working Party analyzed the data of 603 patients who were diagnosed with LCH
      between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was
      65 months (range, 0 to 276 mo). Bone was the most frequently affected organ
      (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single
      system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk
      organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ
      involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and
      MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year
      reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS
      rate was lower in patients with RO involvement (P=0.025) and lack of response to
      initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk
      factor for reactivation. Permanent consequences were documented in 99 patients
      (16.4%). Reactivation of disease, MS involvement, and age at diagnosis <= 2 years
      were associated with higher incidence of permanent consequences. This study
      emphasized that further efforts are required to improve survival of MS-RO
      patients and reduce reactivation in younger patients with MS involvement.

PMID- 24276038
TI  - Metachronous neuroblastoma in an infant with germline translocation resulting in
      partial trisomy 2p: a role for ALK?
AB  - A male infant with dysmorphic features, intestinal malrotation, and developmental
      delay was found to have a germline translocation resulting in partial trisomy 2p
      and monosomy 16p. At 3 and 9 months of age, he developed localized neuroblastoma
      in each adrenal, which was managed with surgical resection. Tumors were MYCN non
      amplified, with 2p copy gain consistent with the germline translocation. The
      potential increased risk of neuroblastoma associated with partial trisomy 2p is
      discussed in the context of this and previously published cases, and may be due
      to increased constitutional expression of MYCN and ALK genes, both located within
      the duplicated 2p region. 

PMID- 24276039
TI  - Response of subependymal giant cell astrocytoma with spinal cord metastasis to
      everolimus.
AB  - BACKGROUND: Brain subependymal giant cell astrocytomas (SEGAs) in patients with
      tuberous sclerosis have been reported to respond to everolimus. METHODS: A 15
      year-old male patient with intractable seizures and multiple SEGAs of the brain
      developed leptomeningeal enhancement and multiple metastatic, histologically
      confirmed SEGAs of the spinal cord. He received daily everolimus at a dose of 3
      mg/m for 6 weeks, which was then increased to 6 mg/m. RESULTS: Magnetic resonance
      image of the brain and spine showed significant reduction in the size of SEGAs
      after 6 weeks of treatment. The patient has remained free of progression for 24
      months. Additional benefits included: excellent seizure control, decrease in the
      size of cardiac rhabdomyomas, and improved quality of life. CONCLUSIONS: We
      describe a rare case of metastatic SEGA, which was successfully treated with
      everolimus.

PMID- 24276040
TI  - Prognostic significance of being overweight and obese at diagnosis in children
      with acute lymphoblastic leukemia.
AB  - This study tested the hypothesis that being overweight/obese at diagnosis of
      childhood ALL was related to risk of relapse. In a national cohort of 1033
      patients from the UK, there was no evidence that weight status at diagnosis was
      related significantly to risk of relapse: log-rank test (P=0.90) with overweight
      and obesity as the exposure (n=917); individual (P=0.42) and stepwise (P=0.96)
      proportional hazards models, with BMI Z score as the exposure. The study does not
      support the hypothesis that being overweight/obese at diagnosis impairs prognosis
      in childhood ALL in the UK. 

PMID- 24276041
TI  - Perception of Indian parents on health-related quality of life of children during
      maintenance therapy of acute lymphoblastic leukemia: a comparison with siblings
      and healthy children.
AB  - BACKGROUND: Advancements in treatment have improved the prognosis of children
      with acute lymphoblastic leukemia (ALL). Therefore, there is a need to explore
      health-related quality of life (HRQOL) in depth, specifically in maintenance
      therapy, where the available data are minimal. This study was conducted to assess
      the varied items listed in the domains of HRQOL of Children with ALL during
      maintenance therapy from a parent's perspective. METHODS: Forty children on the
      maintenance therapy of ALL, 40 siblings, and 40 healthy children were enrolled,
      and the HRQOL was assessed by parent proxy reports and child self-reports using
      PedsQL generic core 4.0 in local language. RESULTS: Parents significantly
      overrated the HRQOL of ALL patients, their siblings, and healthy children in
      comparison with child self-report in all domains of health. The HRQOL of children
      with ALL on maintenance therapy was significantly poorer than siblings and
      healthy children, but their ability to self-care, household work, attentiveness,
      and ability to do homework were not affected as per parents' reports. Parents
      reported that absenteeism because of sickness and hospital visits was more among
      children with ALL than siblings and healthy children. Children with ALL had
      emotional problems such as fear, anger, sleeping problems, and worries. In a
      social health domain, parents reported difficulty in competing among children
      with ALL. The HRQOL of siblings was as good as healthy children in physical,
      social, and school health domains as per parents' reports. CONCLUSIONS: In our
      cohort, parents overrated HRQOL in all groups of children. The study identified
      the various items in each domain of HRQOL that were affected in children with ALL
      from parents' perspective; this would guide health care professionals to focus on
      these specific items so as to improve the overall HRQOL of children with ALL.

PMID- 24276042
TI  - Hepatic sinusoidal obstruction syndrome during chemotherapy for childhood
      medulloblastoma: report of a case and review of the literature.
AB  - Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive
      disease, is a well-recognized toxic complication after autologous and allogeneic
      hematopoietic stem cell transplant, during treatment of Wilms tumor and
      rhabdomyosarcoma associated with actinomycin-D, and during acute lymphoblastic
      leukemia therapy due to oral 6-thioguanine. However, its occurrence in the
      context of chemotherapy regimens for other childhood malignancies is rare. We
      report a 5-year-old girl with high-risk anaplastic medulloblastoma, who developed
      severe HSOS during her second cycle of maintenance chemotherapy, consisting of
      vincristine, cisplatin, and cyclophosphamide. She was treated with defibrotide
      with complete resolution of the HSOS. These findings and a review of the
      literature, highlight the occurrence of HSOS in children outside the established
      settings of hematopoietic stem cell transplantation, Wilms tumor,
      rhabdomyosarcoma, and acute lymphoblastic leukemia. 

PMID- 24276043
TI  - Ewing sarcoma/peripheral primitive neuroectodermal tumor in the adrenal gland of
      an adolescent: a case report and review of the literature.
AB  - Ewing sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNETs) typically
      occur in the long or flat bones, the chest wall, extraskeletal soft tissue, or
      less frequently, in solid organs. They can arise from anywhere in the body;
      however, ES/pPNETs arising from the adrenal gland are very rare, especially in
      children and adolescents. Herein, the authors report a case of an ES/pPNET in the
      adrenal gland of a 17-year-old girl, who was successfully treated with a
      multimodal treatment, with a brief review of the pertinent literature. 

PMID- 24276044
TI  - Gastrointestinal stromal tumor in a newborn diagnosed in prenatal period: a case
      report and review of literature.
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of
      the gastrointestinal tract. Only 1.5% to 2% of all GISTs are observed in children
      and adolescents. Most of the pediatric cases are between 10 and 18 years of age,
      with a median age of 13 years. GIST is extremely rare in the newborn period. We
      could find only 5 reports on the neonatal cases. Herein, we have reported a case
      with abdominal tumor that was identified by prenatal ultrasonography and magnetic
      resonance imaging, and diagnosed as GIST on the seventh day of life. We have also
      reviewed the neonatal GIST cases reported in the English literature. 

PMID- 24276045
TI  - Distant metastatic spread of molecularly proven infantile fibrosarcoma of the
      chest in a 2-month-old girl: case report and review of literature.
AB  - Infantile fibrosarcoma (IFS) is a malignant neoplasm, arising in children younger
      than 2 years of age and with a hallmark chromosomal translocation
      t(12;15)(p13;q26) encoding an ETV6-NTRK3 fusion oncoprotein. A review of the
      world literature found no reported cases of molecularly proven IFS with distant
      metastatic spread at presentation. We report the case of a 2-month-old infant
      girl presenting with a chest wall primary IFS bearing and expressing the ETV6
      NTRK3 fusion, who had several pulmonary metastatic deposits at diagnosis. She
      achieved complete remission with chemotherapy and surgery. To our knowledge, this
      is the first reported case of molecularly proven IFS with distant metastatic
      spread. 

PMID- 24276046
TI  - Clinical and laboratory parameter dynamics as markers of blood stream infections
      in pediatric oncology patients with fever and neutropenia.
AB  - BACKGROUND: Identifying markers associated with blood stream infection (BSI) in
      children with fever and neutropenia (FN) could lead to a substantial reduction in
      unnecessary treatment. STUDY OBJECTIVE: The aim of this study was to determine
      the association between clinical/laboratory parameters and BSI in pediatric
      oncology patients with FN. METHODS: This prospective study was conducted between
      2007 and 2010 at the Pediatric oncology unit. Clinical and laboratory parameters
      were obtained from all hospitalized FN patients. Linear regression and trends
      were calculated to determine the association between clinical/laboratory
      parameters and BSI. RESULTS: Of the 195 FN episodes in 73 children, BSIs were
      identified in 38 (19%) episodes. Gram-positive bacteria, gram-negative bacteria,
      and fungi caused 47%, 43%, and 10% of all BSIs, respectively. Mean fever duration
      was longer in the BSI group (5 d) compared with the non-BSI group (2 d, P=0.01).
      Mean (+/-SD) monocyte count at admission was lower in the BSI group compared with
      the non-BSI group (0.06+/-0.1 vs. 0.14+/-0.33 cells/mm, respectively, P=0.05).
      Mean C-reactive protein (CRP) levels at hospitalization days 5 to 8 were higher
      in children with BSI (P<0.001). Increment trends of monocyte and platelet levels
      and decrement trend of CRP levels were noted in the BSI group but not in the non
      BSI group (P<0.01 for all). CONCLUSIONS: Prolonged fever, lower monocyte count at
      admission, higher CRP levels between the fifth and the eighth hospitalization
      days, increment trends of monocyte and platelet levels, and CRP level decrement
      were associated with BSI. These factors may serve as markers for BSI in pediatric
      oncology patients with FN.

PMID- 24276048
TI  - Propofol and additives in studies evaluating inflammatory responses.

PMID- 24276047
TI  - A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA)
      antagonist, administered in combination with chemotherapy in children with
      relapsed acute lymphoblastic leukemia (ALL): a report from the therapeutic
      advances in childhood leukemia and lymphoma (TACL) consortium.
AB  - To address the therapeutic challenges in childhood relapsed ALL, a phase 1 study
      combining a survivin mRNA antagonist, EZN-3042, with reinduction chemotherapy was
      developed for pediatric patients with second or greater bone marrow relapses of B
      lymphoblastic leukemia. EZN-3042 was administered as a single agent on days -5
      and -2 and then in combination with a 4-drug reinduction platform on days 8, 15,
      22, and 29. Toxicity and the biological activity of EZN-3042 were assessed. Six
      patients were enrolled at dose level 1 (EZN-3042 2.5 mg/kg/dose). Two dose
      limiting toxicities were observed: 1 patient developed a grade 3 gamma-glutamyl
      transferase elevation and another patient developed a grade 3 gastrointestinal
      bleeding. Downmodulation of survivin mRNA and protein were assessed after single
      agent dosing and decreased expression was observed in 2 of 5 patients with
      sufficient material for analysis. Although some biological activity was observed,
      the combination of EZN-3042 with intensive reinduction chemotherapy was not
      tolerated at a dose that led to consistent downregulation of survivin expression.
      The trial was terminated following the completion of dose level 1, after further
      clinical development of this agent was halted. 

PMID- 24276051
TI  - Firearm legislation and gun-related fatalities.

PMID- 24276052
TI  - Firearm legislation and gun-related fatalities.

PMID- 24276053
TI  - Firearm legislation and gun-related fatalities--reply.

PMID- 24276054
TI  - Inappropriate use of lumbar magnetic resonance imaging: limitations and potential
      solutions.

PMID- 24276055
TI  - Inappropriate use of lumbar magnetic resonance imaging: limitations and potential
      solutions--reply.

PMID- 24276056
TI  - Topical anesthetic-induced methemoglobinemia and veterans affairs hospitals.

PMID- 24276057
TI  - Topical anesthetic-induced methemoglobinemia and veterans affairs hospitals-
      reply.

PMID- 24276059
TI  - Prostate-specific antigen testing in france.

PMID- 24276060
TI  - Modulation of quinate: NAD(+) oxidoreductase activity through reversible
      phosphorylation in carrot cell suspensions.
AB  - Quinate: NAD(+) oxidoreductase (EC 1.1.1.24) from carrot cells was deactivated by
      incubating partially purified extract with MgCl2 at 30 degrees C. The
      deactivation process was prevented by adding fluoride, a phosphatase inhibitor.
      Once inactivated, the enzyme could recover its initial activity on incubation
      with ATP-Mg either in combination with or not in combination with an exogenous
      protein kinase. (32)PO4 was incorporated into the purified enzyme when the cell
      cultures were supplemented with labeled phosphate in vivo. Moreover, (32)P from
      [gamma-(32)P]ATP was incorporated into the reductase when the enzyme was
      reactivated in the presence of protein kinase. From these results, it is
      concluded that the activation-inactivation process is due to phosphorylation
      dephosphorylation of quinate:NAD(+) oxidoreductase. 

PMID- 24276061
TI  - Protein synthesis in germinating pollen of Petunia: role of proline.
AB  - Pollen of Petunia hybrida was germinated in artificial medium. At the beginning
      of the incubation, a large amount of proline, which comprises about half of the
      total free amino acid pool, was released into the medium. Part of this proline is
      reutilized by the pollen. Uptake of radioactive amino acids and their
      incorporation into proteins were studied. The highest rate of protein synthesis
      was found directly after the onset of germination. The endogenous free proline
      pool was found to be compartmentalized; one of the compartments is the protein
      precursor pool; its size is probably much less than 50% of the total free proline
      in the pollen. 

PMID- 24276062
TI  - The effects of colchicine and gibberellic acid on growth and microtubules in
      excised lettuce hypocotyls.
AB  - The effect of colchicine on growth and microtubules in H2O-and gibberellic acid
      (GA3)-treated hypocotyls of lettuce (Lactuca sativa L. cv. Arctic) was examined.
      Hypocotyls of seedlings from gamma-irradiated as well as non-irradiated seedlings
      were used in order to establish that the drug was affecting cell elongation and
      not cell division. Although colchicine inhibited elongation of GA3-treated
      hypocotyl sections at concentrations as low as 1 MUM, it did not affect the
      growth of sections. Rather, colchicine treatment caused a reorientation of the
      plane of cell expansion. Lumicolchicine had no effect on elongation of hypocotyl
      sections at a concentration (100 MUM) at which colchicine abolished GA3-induced
      elongation. Colchicine was only effective in reorienting the plane of growth in
      light; in darkness, it inhibited both radial and longitudinal cell expansion.
      Analogs of colchicine as well as other antimicrotubular agents were ineffective
      in changing the polarity of growth in lettuce. Electron microscopy showed that
      transversely oriented microtubules were numerous in the cortical cytoplasm
      adjacent to the longitudinal wall of freshly excised hypocotyl sections.
      Incubation in GA3 did not change the number or orientation of these microtubules,
      while incubation in H2O caused a reduction in their number and altered their
      distribution. Colchicine abolished microtubules under all conditions of
      incubation tested, but did not affect other characteristics of cell
      ultrastructure. 

PMID- 24276063
TI  - Leaf senescence in a non-yellowing mutant of Festuca pratensis : I. Chloroplast
      membrane polypeptides.
AB  - Soluble and thylakoid membrane polypeptides from senescing leaf tissue of Rossa,
      a normal yellowing Festuca pratensis genotype, were fractionated by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis and compared with those of
      the non-yellowing mutant Bf 993. Subunits of ribulose-1,5-bisphosphate
      carboxylase were the major soluble polypeptides and declined to low levels in
      senescing leaves of both genotypes. The major thylakoid polypeptides were those
      associated with the chlorophyllprotein complexes CPI and CPII. The levels of all
      thylakoid polypeptide species fell during senescence of Rossa leaf tissue but
      Bf993 lamellae retained CPI, CPII and a number of other hydrophobic low molecular
      weight polypeptides. The increasing hydrophobicity and decreasing protein
      complement of Bf 993 thylakoids were reflected in a fall in membrane density from
      1.16 to 1.13 g cm(-3) over 8 d of senescence and a decline in the extractability
      of chlorophyll-containing membranes in the same period. In Bf993 the molar ratio
      of chlorophyll to hydrophobic membrane protein increased from 92 at day 0 to 296
      at day 8. In the same time the ratio for Rossa increased from 88 to 722 and 8 d
      senesced Rossa tissue yielded less than 2% of the solvent-soluble protein it
      contained at day 0 as compared with 24% for the protein of Bf993. These results
      are discussed in relation to the nature of the non-yellowing lesion. 

PMID- 24276064
TI  - Leaf senescence in a non-yellowing mutant of Festuca pratensis : II. Proteolytic
      degradation of thylakoid and stroma polypeptides.
AB  - The acid proteinases (E.C. 3.4.4.?) of mature, nonsenescent Festuca pratensis
      leaf tissue were fractionated into one major and three minor activities by ion
      exchange chromatography. During senescence of leaf sections in darkness there was
      a general increase in total proteinase activity but no qualitative alteration in
      the proteinase complement. The pattern of proteinases in the nonyellowing mutant
      Bf 993 was essentially identical to that of the normal genotype Rossa. The pH
      responses of proteinases from senescent Bf 993 and Rossa tissue were measured
      using as substrates (14)C-labelled protein fractions prepared from barley
      seedlings. These fractions were: ribulose bisphosphate carboxylase; low molecular
      weight soluble protein; ethylene diamine tetraacetate soluble thylakoid protein;
      chloroform: methanol soluble thylakoid protein; and residual protein. For each
      substrate, the pH optimum was 5-6, there was a shoulder on the neutral-alkaline
      side of the pH curve and hydrolase activity was stimulated by borate at high pH.
      The responses of Bf 993 proteinases were very similar to those of Rossa. These
      results suggest that it is the accessibility of thylakoid proteins to proteinase
      action rather than proteinase per se that is impaired in the non-yellowing
      mutant. 

PMID- 24276065
TI  - Phytochrome-controlled extension growth of Avena sativa L. seedlings : I. Kinetic
      characterization of mesocotyl, coleoptile, and leaf responses.
AB  - The effects of continuous red and far-red light and of brief light pulses on the
      growth kinetics of the mesocotyl, coleoptile, and primary leaf of intact oat
      (Avena sativa L.) seedlings were investigated. Mesocotyl lengthening is strongly
      inhibited, even by very small amounts of Pfr, the far-red light absorbing form of
      phytochrome (e.g., by [Pfr]~0.1% of total phytochrome, established by a 756-nm
      light pulse). Coleoptile growth is at first promoted by Pfr, but apparently
      inhibited later. This inhibition is correlated in time with the rupturing of the
      coleoptile tip by the primary leaf, the growth of which is also promoted by
      phytochrome. The growth responses of all three seedling organs are fully
      reversible by far-red light. The apparent lack of photoreversibility observed by
      some previous investigators of the mesocotyl inhibition can be explained by an
      extremely high sensitivity to Pfr. Experiments with different seedling parts
      failed to demonstrate any further obvious interorgan relationship in the light
      mediated growth responses of the mesocotyl and coleoptile. The organspecific
      growth kinetics, don't appear to be influenced by Pfr destruction. Following an
      irradiation, the growth responses are quantitatively determined by the level of
      Pfr established at the onset of darkness rather than by the actual Pfr level
      present during the growth period. 

PMID- 24276066
TI  - Phytochrome-controlled extension growth of Avena sativa L. seedlings : II.
      Fluence rate response relationships and action spectra of mesocotyl and
      coleoptile responses.
AB  - Fluence rate response curves for light-induced inhibition of mesocotyl growth and
      promotion of coleoptile growth in etiolated Avena sativa L. (cv. Victory) were
      developed. The irradiation time was 24 h. Fluence rates between 10(-6) and 10(5)
      nmol m(-2)s(-1) and 30 wavelengths between 563 and 1,093 nm were used. The main
      conclusions are as follows: 1. Both organs exhibit a low fluence rate response as
      well as a high fluence rate response. 2. The mesocotyl response is more sensitive
      to light than the coleoptile response. 3. The low fluence rate response of the
      mesocotyl shows a threshold of sensitivity at about 10(-7) nmol m(-2)s(-1) (i.e.,
      total fluence of 5.10(-2) nmol m(-2) during the experiment) in the red and a
      saturation (about 70% inhibition of growth) at 10(-4) nmol m(-2)s(-1) (50 nmol m(
      2)). 4. The action spectrum for the low fluence rate response parallels the Pr
      absorption spectrum. Alterations induced by screening are discussed. 5. The
      action spectrum demonstrates an exponential decrease in apparent photoconversion
      cross-section (Pr->Pfr) up to about 800 nm. Between 800 and 1,093 nm the
      photoconversion cross-section is only weakly dependent on wavelength. 6. The
      action spectrum for the high fluence rate response shows a broad peak in the red,
      a trough at 723 nm, and a sharp peak at 740-750 nm. 

PMID- 24276067
TI  - Ultrastructure of cell wall and plugs of tobacco pollen tubes after chemical
      extraction of polysaccharides.
AB  - Tobacco pollen tubes grown in vitro and from pollinated tobacco styles were
      treated by chemical solvents to remove one or more of the following
      polysaccharides from the tube walls: pectin (ethylenediamine tetraacetic acid);
      hemicellulose (alkali); callose (alkali; potassium hypochlorite); cellulose
      (cuprammonium); and all polysaccharides with exception of cellulose (H2O2/glacial
      acetic acid). Both the inner tube wall, which we had regarded as the secondary
      wall, and the plugs contained, in addition to callose, microfibrils of cellulose
      and "non-cellulosic" microfibrils that had "pectin-like" properties. When using
      the expressions callosic or callose layer and callose plugs in reference to
      pollen tubes, one should realize that they do not imply the exclusive presence of
      callose in the inner tube wall layer and its localized thickenings. 

PMID- 24276068
TI  - Accessory polypeptides in phycobilisomes of red algae and cyanobacteria.
AB  - Phycobilisomes of red algae and cyanobacteria contain small amounts of
      nonpigmented polypeptides in addition to the major constituent biliprotein
      pigments. The localization of these polypeptides is analyzed by gel
      electrophoresis of phycobilisome fragments obtained by selective dissociation and
      subsequent separation. Five groups of biliprotein aggregates are determined,
      belonging to the 6, 11, 16, 18 and 23 S categories. Accessory nonpigmented high
      molecular weight proteins (80,000 MW) are exclusively bound to phycobilisome core
      fractions and thylakoids, thus apparently serving as links between the
      phycobilisomes and the photosynthetic units of the thylakoids. In contrast,
      smaller nonpigmented accessory polypeptides of 20,000 to 60,000 MW are preferably
      found in the peripheral biliprotein stacks. They may either form a compatible
      link between the phycobilisome core and periphery or bind and co-polymerize with
      hexameric biliproteins in the peripheral stacks to enhance or effect binding of
      the aggregates. Furthermore, they may determine the arrangement and composition
      of the phycobilisomes during development and chromatic adaptation. 

PMID- 24276069
TI  - Chloroplast development in low light-grown barley seedlings.
AB  - Segments of 7-d low light-grown barley laminae cut at 0.5 cm intervals up from
      the intercalary meristem were examined ultrastructurally and biochemically. The
      different regions upwards showed the succession of plastid development in light
      grown tissues of eoplasts, amyloplasts, amoeboid, immature and mature plastids as
      described by Whatley (1977). Semi-crystalline bodies were detected in all of
      them. The eoplast-amyloplast regions are characterised by a greater proportion of
      mitochondria and high levels of ATP and 3-phosphoglyceric acid, together with low
      levels of inorganic phosphate conducive to the activation of ADP glucose
      pyrophosphorylase. The amoeboid and immature plastid regions have higher levels
      of inhibitory phosphate and starch breakdown may be responsible for the release
      of metabolites and energy for development. Segments containing amoeboid and
      immature plastids also have reduced levels of ATP (and 3-phosphoglyceric acid) as
      photosynthetic components are synthesised. Using ultrastructural assessments of
      areas of thylakoids, first beta-carotene and violaxanthin, followed by
      chlorophyll a and lutein and, lastly, chlorophyll b are concentrated in the
      developing lamellar systems of the immature and mature chloroplasts. The
      formation of additional membraneous material which spreads these pigment systems
      over a greater thylakoid area within the plastids is the final stage of plastid
      morphogenesis in low light-grown seedlings. 

PMID- 24276070
TI  - The endogenous gibberellins of vegetative and reproductive tissue of G2 peas.
AB  - The gibberellins (GAs) of both vegetative (leaves and stems) and reproductive
      (pods and seeds) tissue of the G2 strain of peas Pisum sativum L. were
      characterized in purified extracts by a combination of sequential silicic-acid
      partition column chromatography, and gas chromatography-mass spectrometry.
      Gibberellins A19, A20, A29 and an A29 catabolite were identified in both types of
      tissue. Gibberellins A9, A17 and A44 were also found in pods and seeds. 

PMID- 24276071
TI  - Mass spectrometric measurement of zeatin glycoside levels in Vinca rosea L. crown
      gall tissue.
AB  - The range of zeatin glycosides found in crown gall tissue of Vinca rosea L. has
      been quantified using a mass spectrometric isotope dilution procedure. Problems
      in the quantitative analysis of cytokinins in plant extracts are discussed. 

PMID- 24276072
TI  - The Golgi apparatus in developing endosperm of wheat (Triticum aestivum L.).
AB  - The ultrastructure and distribution of the Golgi apparatus in developing wheat
      endosperm was investigated using a zinc iodide-osmium tetroxide staining complex
      in conjunction with low and high voltage electron microscopy. Dictyosomes were
      numerous in starchy endosperm and aleurone at 15 days after anthesis, and during
      the period of rapid storage protein deposition 25 d after anthesis. Fewer
      dictyosomes were seen in maturing endosperm. Two types of vesicles were
      associated with the dictyosomes; small, heavily-stained vesicles were sited at
      the ends of fine tubules which extend from the cisternae, and larger less-stained
      vesicles were associated with the periphery of the cisternae. Stereo-pairs of
      micrographs up to 1 MUm thick were taken to demonstrate the interconnections
      between cisternal and tubular endoplasmic reticulum. Elements of tubular ER were
      closely associated with dictyosomes, but connections were not observed. These
      results are discussed in relation to the transport of endosperm storage proteins
      from their site of synthesis on the cisternal ER to their site of storage, the
      protein bodies. 

PMID- 24276073
TI  - Variations in ribulose 1,5-bisphosphate carboxylase protein levels, activities
      and subcellular distribution during photoautotrophic batch culture of
      Chlorogloeopsis fritschii.
AB  - Ribulose 1,5-bisphosphate (RuBP) carboxylase is present in the cytoplasm and
      carboxysomes (polyhedral bodies) of the cyanobacterium Chlorogloeopsis fritschii.
      In vitro enzyme activities have been measured throughout photoautotrophic batch
      culture, together with RuBP carboxylase protein concentrations, determined by
      rocket immunoelectrophoresis. Enzyme activities and protein levels in the
      cytoplasmic and carboxysomal fractions varied in an apparently inverse manner
      during growth. The RuBP carboxylase activities per unit enzyme protein were
      maximal in late lag phase/early exponential phase for both cellular enzyme pools.
      Both rates per unit enzyme protein declined during exponential phase, cytoplasmic
      enzyme activity remaining consistently higher than that of the carboxysomal
      enzyme. Activities per unit cytoplasmic and carboxysomal enzyme protein showed
      very low, similar rates in late stationary phase and death phase. Dialysis
      experiments indicated that such changes were not due to interference in activity
      assays by soluble endogenous effectors. Major shifts in the subcellular
      distribution of RuBP carboxylase protein were found versus culture age, enzyme
      protein levels being predominantly carboxysomal in lag phase, mainly soluble in
      exponential phase and then mainly carboxysomal again in stationary/death phase.
      The data are discussed in terms of carboxysome function and the question of
      control of RuBP carboxylase synthesis in cyanobacteria. 

PMID- 24276074
TI  - A multicentre, prospective, randomised, double-blind study to measure the
      treatment effectiveness of abobotulinum A (AboBTXA) among women with refractory
      interstitial cystitis/bladder pain syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: To determine if abobotulinumtoxin A (AboBTXA) is an
      effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS).
      METHODS: We performed a double-blind study of 54 women with severe, refractory IC
      from three referral centres whom we randomly allocated to treatment with
      hydrodistension + injection of normal saline or to hydrodistension + injection
      with AboBTXA. The O'Leary-Sant questionnaire consists of problem (OLS-PI) and
      symptom (OLS-PI) index scores, and bladder diary data were compared between
      AboBTXA and control patients at baseline and at 3 months of follow-up.
      Measurements were made beyond 3 months, but no further randomised comparison was
      possible due to the ability of nonresponsive patients in either group to have
      AboBTXA treatment. RESULTS: Complete data were available in 50 patients, and in
      both groups, OLS questionnaires showed improvement at 3 months. Only the OLS-PI
      was improved in the AboBTXA group (p = 0.04). At 3 months, no difference was
      found in either OLS-SI or total OLS score. Twelve patients had urinary tract
      infection (UTI) treated during the follow-up period, which confounded results. In
      the 38 patients without UTI, there was improvement in total OLS score (p = 0.02),
      OLS-PI (0.08), and OLS-SI (p = 0.008) for the AboBTXA group at 3 months. Only
      five AboBTXA compared with two control patients had a 50% reduction in OLS score.
      CONCLUSIONS: For chronic refractory IC/BPS patients, AboBTXA was associated with
      no overall improvement in total OLS score, although significant benefit was noted
      in a small number of patients. The absence of posttreatment UTI was associated
      with a better response to AboBTXA.

PMID- 24276075
TI  - Does bariatric surgery change olfactory perception? Results of the early
      postoperative course.
AB  - PURPOSE: Changes of food preference toward foods with low caloric density have
      been demonstrated after bariatric surgery and may contribute to sustained body
      weight loss. It has been hypothesized that olfactory perception as an integral
      part of food selection might be altered after bariatric surgery. METHODS:
      Sniffin' Sticks(r) were used to investigate the olfactory perception of morbidly
      obese patients undergoing either Roux-en-Y gastric bypass (RYGB, n = 15) or
      sleeve gastrectomy (SG, n = 15) before 1, 6, 12, and 24 weeks after surgery.
      Obese patients without surgical intervention served as controls (CG, n = 12).
      Results are presented using the testing odor threshold, discrimination, and
      identification score (TDI; higher scores indicate better olfactory perception).
      Body weight loss was recorded. RESULTS: Initial BMI of the SG group (56.04 +/-
      7.096 kg m(-2)) was higher compared to the BMI of the RYGB (48.71 +/- 6.49 kg m(
      2)) and CG (50.35 +/- 6.78 kg m(-2)); p = 0.011. Body weight loss among the
      surgical groups was not different (p = 0.011) while controls did not lose weight.
      Mean baseline TDI scores were significantly lower in the SG group 27.1 +/- 3.9
      vs. 32.6 +/- 3.6 (RYGB) and 32.1 +/- 5.3 (CG), respectively, whereas there were
      after 24 weeks no changes in RYGB and CG patients; the TDI score in the SG group
      increased significantly to 31.1 +/- 3.5 (p < 0.01). CONCLUSIONS: Our data suggest
      that a substantial body weight loss per se does not affect olfactory perception.
      However, our results point towards improved olfactory perception after sleeve
      gastrectomy but not Roux-en-Y gastric bypass.

PMID- 24276076
TI  - CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting
      agents.
AB  - As the first in class steroid 17alpha-hydroxylase/C17,20-lyase (CYP17) inhibitor,
      abiraterone acetate (of which the active metabolite is abiraterone) has been
      shown to improve overall survival in patients with castration-resistant prostate
      cancer (CRPC)--in those who are chemotherapy-naive and those previously treated
      with docetaxel. Furthermore, the clinical success of abiraterone demonstrated
      that CRPC, which has previously been regarded as an androgen-independent disease,
      is still driven, at least in part, by androgens. More importantly, abiraterone is
      a 'promiscuous' drug that interacts with a number of targets, which dictate its
      clinical benefits and adverse effects profile. Besides CYP17 inhibition,
      abiraterone acts as an antagonist to the androgen receptor and inhibits 3beta
      hydroxysteroid dehydrogenase--two effects that potentially contribute to its
      antitumour effects. However, the inhibition of the 17alpha-hydroxylase activity
      of CYP17, CYP11B1 and a panel of hepatic CYP enzymes leads to adverse effects and
      toxicities that include secondary mineralocorticoid excess. Abiraterone is also
      associated with increased incidence of cardiac disorders. Under such
      circumstances, development of new CYP17 inhibitors as an additional line of
      defence is urgently needed. To achieve enhanced clinical benefits, new strategies
      are being explored that include selective inhibition of the C17,20-lyase activity
      of CYP17 and multi-targeting strategies that affect androgen synthesis and
      signalling at different points. Some of these strategies-including the drugs
      orteronel, VT-464 and galeterone--are supported by preclinical data and are being
      explored in the clinic.

PMID- 24276080
TI  - Prostate cancer: Intermediate efficacy end points to assess modern therapies.

PMID- 24276081
TI  - Prostate cancer: The high-risk dichotomy.

PMID- 24276082
TI  - Bladder cancer: Progress in defining progression in NMIBC.

PMID- 24276084
TI  - BPH: Promising future for the prostatic urethral lift.

PMID- 24276086
TI  - Trojan horses: drug culprits associated with antineutrophil cytoplasmic
      autoantibody (ANCA) vasculitis.
AB  - PURPOSE OF REVIEW: Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis is a
      systemic autoimmune disease resulting in small-vessel inflammation caused by
      pathogenic autoantibodies directed against proteinase 3 or myeloperoxidase. Legal
      drug culprits have been implicated as causative agents in secondary forms of
      disease, and a recent burst of reports also implicate levamisole-adulterated
      cocaine as a culprit. RECENT FINDINGS: Here, we briefly discuss all drug culprits
      associated with ANCA vasculitis and then focus on clinical, serologic,
      therapeutic and mechanistic aspects of four main drug culprits receiving
      attention of late, namely hydralazine, minocycline, propylthiouracil (PTU) and
      levamisole-adulterated cocaine. SUMMARY: Hydralazine, minocycline,
      propylthiouracil and levamisole-adulterated cocaine use should be closely
      considered in any patient where ANCA vasculitis is entertained given the wide use
      of these drugs in the community. Furthermore, medical practitioners should test
      urine for the presence of cocaine in any patient with presumed ANCA vasculitis,
      and if positive, then urine should also be tested for levamisole. Clinical
      features can be severe requiring not only drug cessation and supportive care, but
      also immunosuppression, plasma exchange in severe cases and dialysis as needed.
      Clinical trial investigators should strongly consider excluding patients with
      drug-induced forms of disease and mechanistic inroads are greatly needed in these
      secondary forms of disease to help elucidate the underlying cause and
      pathogenesis of ANCA vasculitis.

PMID- 24276085
TI  - The hippo pathway is activated and is a causal mechanism for adipogenesis in
      arrhythmogenic cardiomyopathy.
AB  - RATIONALE: Mutations in the intercalated disc proteins, such as plakophilin 2
      (PKP2), cause arrhythmogenic cardiomyopathy (AC). AC is characterized by the
      replacement of cardiac myocytes by fibro-adipocytes, cardiac dysfunction,
      arrhythmias, and sudden death. OBJECTIVE: To delineate the molecular pathogenesis
      of AC. METHODS AND RESULTS: Localization and levels of selected intercalated disc
      proteins, including signaling molecules, were markedly reduced in human hearts
      with AC. Altered protein constituents of intercalated discs were associated with
      activation of the upstream Hippo molecules in the human hearts, in Nkx2.5
      Cre:Dsp(W/F) and Myh6:Jup mouse models of AC, and in the PKP2 knockdown HL-1
      myocytes (HL-1(PKP2:shRNA)). Level of active protein kinase C-alpha isoform,
      which requires PKP2 for activity, was reduced. In contrast, neurofibromin 2 (or
      Merlin), a molecule upstream of the Hippo pathway and that is inactivated by
      protein kinase C-alpha isoform, was activated. Consequently, the downstream Hippo
      molecules mammalian STE20-like protein kinases 1/2 (MST1/2), large tumor
      suppressor kinases 1/2 (LATS1/2), and Yes-associated protein (YAP) (the latter is
      the effector of the pathway) were phosphorylated. Coimmunoprecipitation detected
      binding of phosphorylated YAP, phosphorylated beta-catenin, and junction protein
      plakoglobin (the latter translocated from the junction). RNA sequencing,
      transcript quantitative polymerase chain reaction, and reporter assays showed
      suppressed activity of SV40 transcriptional enhancer factor domain (TEAD) and
      transcription factor 7-like 2 (TCF7L2), which are transcription factors of the
      Hippo and the canonical Wnt signaling, respectively. In contrast, adipogenesis
      was enhanced. Simultaneous knockdown of Lats1/2, molecules upstream to YAP,
      rescued inactivation of YAP and beta-catenin and adipogenesis in the HL
      1(PKP2:shRNA) myocytes. CONCLUSIONS: Molecular remodeling of the intercalated
      discs leads to pathogenic activation of the Hippo pathway, suppression of the
      canonical Wnt signaling, and enhanced adipogenesis in AC. The findings offer
      novel mechanisms for the pathogenesis of AC.

PMID- 24276087
TI  - Emerging therapies in antineutrophil cytoplasm antibody-associated vasculitis.
AB  - PURPOSE OF REVIEW: The current standard therapy for antineutrophil cytoplasm
      antibody-associated vasculitis (AAV), high-dose glucocorticoid and
      cyclophosphamide followed by azathioprine, has improved the disease prognosis.
      However, there are still unmet needs. For example, reducing relapse risk and
      glucocorticoid toxicity. Newer therapies are needed. RECENT FINDINGS: Potential
      newer drugs are emerging following a better understanding of disease mechanisms
      and the availability of targeted therapies to B cells, T cells, proinflammatory
      cytokines and complement. Rituximab, an anti-CD20 monoclonal antibody, has proven
      efficacy in remission induction therapy for AAV, and two trials with rituximab as
      remission maintenance therapy are ongoing. Clinical trials evaluating
      mycophenolate mofetil as remission induction therapy, gusperimus, belimumab and
      complement factor C5a inhibition are also ongoing, and many other potential
      candidates are being investigated both clinically and experimentally. SUMMARY: B
      cell therapy is now an established treatment in AAV and several other therapies
      are under evaluation. However, the unmet need in vasculitis therapy remains large
      and newer therapies either alone or in combination will need to both improve
      efficacy and permit reductions in glucocorticoid and immunosuppressive exposure.

PMID- 24276088
TI  - Genome-wide association studies to advance our understanding of critical cell
      types and pathways in rheumatoid arthritis: recent findings and challenges.
AB  - PURPOSE OF REVIEW: A significant number of loci implicated in rheumatoid
      arthritis (RA) susceptibility have been highlighted by genome-wide association
      studies (GWAS). Here, we review the recent advances of GWAS in understanding the
      genetic architecture of RA, and place these findings in the context of RA
      pathogenesis. RECENT FINDINGS: Although the interpretation of GWAS findings in
      the context of the disease biology remains challenging, interesting observations
      can be highlighted. Integration of GWAS results with cell-type specific gene
      expression or epigenetic marks have highlighted regulatory T cells and CD4 memory
      T cells as critical cell types in RA. In addition, many genes in RA loci are
      involved in the nuclear factor-kappaB signaling pathway or the Janus kinase (JAK)
      signal transducers and activators of transcription (STAT) signaling pathway. The
      observation that these pathways are targeted by several approved drugs used to
      treat the symptoms of RA highlights the promises of human genetics to provide
      insights in the disease biology, and help identify new therapeutic targets.
      SUMMARY: These findings highlight the promises and need of future studies
      investigating causal genes and underlined mechanisms in GWAS loci to advance our
      understanding of RA.

PMID- 24276089
TI  - Arthritis and bone loss: a hen and egg story.
AB  - PURPOSE OF REVIEW: In this review, we will discuss the relation between bone loss
      and inflammation in rheumatoid arthritis. RECENT FINDINGS: We highlight recent
      discoveries on the pathomechanisms of bone loss in rheumatoid arthritis and
      challenge traditional concepts by suggesting that bone loss may precede
      inflammation. SUMMARY: During the clinical course of rheumatoid arthritis,
      inflammation is the key trigger for progressive local and systemic bone damage.
      Inflammatory cytokines induce the expression of molecules supporting the
      differentiation of osteoclasts, which are the primary bone-resorbing cells.
      However, bone loss can be observed in patients with recent-onset rheumatoid
      arthritis, suggesting that the start of the destructive phase of disease may be
      much earlier than previously expected. Recent data suggest that bone loss already
      starts during the autoimmune phase of the disease long before inflammation
      starts. Antibodies against citrullinated proteins thereby seem to be an important
      trigger for bone loss in the preclinical disease phase of rheumatoid arthritis.
      Although traditional concepts preferred a 'hen-egg' concept with inflammation
      coming first, later triggering bone loss, new data suggest an alternative 'egg
      hen' concept, where bone loss arises before the clinical disease onset and may be
      important for priming of the joint for susceptibility to chronic inflammation.

PMID- 24276090
TI  - Systematic conversion of single walled carbon nanotubes into n-type
      thermoelectric materials by molecular dopants.
AB  - Thermoelectrics is a challenging issue for modern and future energy conversion
      and recovery technology. Carbon nanotubes are promising active thermoelectic
      materials owing to their narrow bandgap energy and high charge carrier mobility,
      and they can be integrated into flexible thermoelectrics that can recover any
      waste heat. We here report air-stable n-type single walled carbon nanotubes with
      a variety of weak electron donors in the range of HOMO level between ca. -4.4 eV
      and ca. -5.6 eV, in which partial uphill electron injection from the dopant to
      the conduction band of single walled carbon nanotubes is dominant. We display
      flexible films of the doped single walled carbon nanotubes possessing
      significantly large thermoelectric effect, which is applicable to flexible
      ambient thermoelectric modules.

PMID- 24276091
TI  - ["Time is brain". Optimizing prehospital stroke management].
AB  - Acute stroke is one of the main causes of death and chronic disability.
      Thrombolysis, achieved by administering recombinant tissue plasminogen activator
      within 4.5 h, is an effective therapeutic option for ischemic stroke. However,
      less than 2-12 % of patients receive this treatment and a major reason is that
      most patients reach the hospital too late. Several time-saving measures should be
      implemented. Firstly, optimized and continual public awareness campaigns for
      patients should be initiated to reduce delays in notifying the emergency medical
      service. Secondly, emergency medical service personnel should develop protocols
      for prenotification of the receiving hospital. Other suggested measures involve
      educating emergency medical service personnel to systematically use scales for
      recognizing the symptoms of stroke and to triage patients to experienced stroke
      centers. In the future, administering treatment at the emergency site (mobile
      stroke unit concept) may allow more than a small minority of patients to benefit
      from available recanalization treatment options. 

PMID- 24276093
TI  - Developing Singapore as an international medical centre.

PMID- 24276092
TI  - Brain differences in infants at differential genetic risk for late-onset
      Alzheimer disease: a cross-sectional imaging study.
AB  - IMPORTANCE: Converging evidence suggests brain structure alterations may precede
      overt cognitive impairment in Alzheimer disease by several decades. Early
      detection of these alterations holds inherent value for the development and
      evaluation of preventive treatment therapies. OBJECTIVE: To compare magnetic
      resonance imaging measurements of white matter myelin water fraction (MWF) and
      gray matter volume (GMV) in healthy infant carriers and noncarriers of the
      apolipoprotein E (APOE) epsilon4 allele, the major susceptibility gene for late
      onset AD. DESIGN, SETTING, AND PARTICIPANTS: Quiet magnetic resonance imaging was
      performed at an academic research imaging center on 162 healthy, typically
      developing 2- to 25-month-old infants with no family history of Alzheimer disease
      or other neurological or psychiatric disorders. Cross-sectional measurements were
      compared in the APOE epsilon4 carrier and noncarrier groups. White matter MWF was
      compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60
      epsilon4 carriers and 102 noncarriers). Gray matter volume was compared in a
      subset of fifty-nine 6- to 25-month-old infants (23 epsilon4 carriers and 36
      noncarriers), who remained asleep during the scanning session. The carrier and
      noncarrier groups were matched for age, gestational duration, birth weight, sex
      ratio, maternal age, education, and socioeconomic status. MAIN OUTCOMES AND
      MEASURES: Automated algorithms compared regional white matter MWF and GMV in the
      carrier and noncarrier groups and characterized their associations with age.
      RESULTS: Infant epsilon4 carriers had lower MWF and GMV measurements than
      noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and
      medial occipitotemporal regions, areas preferentially affected by AD, and greater
      MWF and GMV measurements in extensive frontal regions and measurements were also
      significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05,
      after correction for multiple comparisons; GMV differences, P < .001, uncorrected
      for multiple comparisons). Infant epsilon4 carriers also exhibited an attenuated
      relationship between MWF and age in posterior white matter regions. CONCLUSIONS
      AND RELEVANCE: While our findings should be considered preliminary, this study
      demonstrates some of the earliest brain changes associated with the genetic
      predisposition to AD. It raises new questions about the role of APOE in normal
      human brain development, the extent to which these processes are related to
      subsequent AD pathology, and whether they could be targeted by AD prevention
      therapies.

PMID- 24276094
TI  - Electrocardiography series. Electrocardiographic T wave abnormalities.
AB  - The causes of abnormal T waves on electrocardiography are multiple and varied.
      Careful clinical history taking and physical examination are necessary for
      accurate identification of the cause of such abnormalities. Subsequent targeted
      specialised cardiac investigations, such as echocardiography or coronary
      angiography, may be of importance in the diagnosis of the underlying cardiac
      pathology. We present two cases of T wave inversions with markedly different
      aetiologies. 

PMID- 24276095
TI  - Clinics in diagnostic imaging (149). Bilateral testicular epidermoid cysts.
AB  - A 33-year-old man presented with a painless, non-growing left testicular mass for
      five years. Preoperative ultrasonography (US) of the scrotum showed a small,
      circumscribed calcific mass in the right testis and another well-defined
      heterogeneous echoic mass with a partially calcified wall in the left testis,
      with avascularity on colour Doppler US. These imaging findings in a clinical
      setting of non-growing testicular masses were highly suggestive of epidermoid
      cysts, thus leading to testis sparing surgery. Histopathology confirmed bilateral
      epidermoid cysts. To the best of our knowledge, only 15 cases of bilateral
      epidermoid cysts have been reported. We discuss the US features of epidermoid
      cyst and its surgical management, as well as various cases of testicular masses. 

PMID- 24276096
TI  - Effectiveness of Montreal Cognitive Assessment for the diagnosis of mild
      cognitive impairment and mild Alzheimer's disease in Singapore.
AB  - INTRODUCTION: Mild cognitive impairment (MCI) is an important clinical entity
      with significant management implications. However, traditional screening tools
      lack the sensitivity needed to detect amnestic MCI (MCI-A). Montreal Cognitive
      Assessment (MoCA) has yet to be validated for the diagnosis of MCI in a
      multiracial society such as Singapore. We thus aimed to study the effectiveness
      of MoCA for the diagnosis of MCI-A in the Singapore population. METHODS: Data on
      patients with MCI-A and mild Alzheimer's disease (AD) was obtained from a
      prospectively collected clinical database between January 2008 and January 2011.
      Patients with no cognitive impairment (NCI) were recruited from among the spouses
      and friends of patients attending the memory clinic. RESULTS: There were a total
      of 212 participants (103 NCI, 49 MCI-A, 60 mild AD). For the diagnosis of MCI-A,
      a MoCA score of < 26 for patients with <= 10 years of education, and a score of <
      27 for patients with > 10 years of education provided a sensitivity of > 94%. For
      the diagnosis of mild AD, a MoCA score of < 24 for patients with <= 10 years of
      education, and a score of < 25 for patients with > 10 years of education provided
      a sensitivity of > 85%. CONCLUSION: In the Singapore population, we recommend
      cutoff scores of 26/27 and 24/25 be used to detect MCI-A and mild AD,
      respectively, when using MoCA. For patients with <= 10 years of education, a +1
      point correction is needed.

PMID- 24276097
TI  - Effect of negative-pressure wound therapy on open fractures of the lower limb.
AB  - INTRODUCTION: Early debridement and coverage has long been regarded as the
      standard of care for open fractures of the lower limb, as infection is a serious
      complication. However, the best time for wound closure remains controversial.
      Negative-pressure wound therapy (NPWT) is thought to result in reduced flap
      infection and failure. To determine the effect of NPWT, we reviewed patients with
      open fractures of the lower limb and compared the rates of infection and flap
      failure in two time-based cohorts. METHODS: Two cohorts of patients (periods 2003
      2004 and 2008-2009) with Gustilo type IIIB open tibial fractures were recruited
      and their outcomes were compared. In the 2003-2004 cohort, wounds were dressed
      with occlusive dressing. In the 2008-2009 cohort, all patients underwent NPWT.
      Data was retrospectively analysed with regard to infection, failure, age, type of
      flap, comorbidities and defect size. The incidences of infection and flap failure
      were further analysed for any statistical difference between the different
      treatment protocols. RESULTS: In the 2003-2004 cohort, 33% of patients developed
      infection and 11% had flap failure. However, in the 2008-2009 cohort, 10% of
      patients developed infection and 6% had flap failure. The difference in the
      incidence of infection was statistically significant between the two cohorts (p =
      0.029). CONCLUSION: Patients in the 2008-2009 cohort had better outcomes, and we
      are of the opinion that performing NPWT may have contributed to this result.

PMID- 24276098
TI  - Poststroke constipation in the rehabilitation ward: incidence, clinical course
      and associated factors.
AB  - INTRODUCTION: Constipation is a common poststroke complication. This study was
      designed to document the incidence and clinical course of poststroke constipation
      in a rehabilitation ward, as well as identify the factors independently
      associated with the condition. METHODS: This retrospective study involved
      patients who were admitted to the rehabilitation ward of our institute due to an
      acute stroke between 1 August 2010 and 31 July 2011. The main outcome measured
      was the incidence of poststroke constipation, defined as the use of laxative
      after stroke, fulfilment of the Rome II diagnostic criteria for functional
      constipation and/or stool impaction. The variables examined were basic
      demographic data, presence of impairment, degree of disability (evaluated using
      the Barthel index), walking ability, medications taken and medical complications.
      RESULTS: Out of the 155 patients who met the inclusion criteria, 123 (79.4%) had
      poststroke constipation. All 123 patients used oral laxatives; 56 received
      additional rectal medications and 13 discontinued their use of laxatives at
      discharge. Patients with poststroke constipation were more likely to have major
      medical complications (p = 0.04). Those who used rectal medications had a higher
      risk of major medical complications than those who used only oral laxatives (p <
      0.01). Infratentorial lesions were an independent predictor of poststroke
      constipation (p = 0.003). More severe disability increased the severity of
      constipation, as indicated by the use of rectal medication. CONCLUSION:
      Poststroke constipation is a common complication during inpatient rehabilitation.
      Healthcare providers should be aware of the incidence of poststroke constipation.
      Further studies are required to establish standard guidelines for screening and
      managing bowel function in patients with stroke.

PMID- 24276099
TI  - Prevalence of nontraumatic foot pain among urban young working women and its
      contributing factors.
AB  - INTRODUCTION: Foot pain is a common problem, especially in women, and studies
      have shown that it is related to footwear. This study was conducted to establish
      the prevalence of nontraumatic foot pain and its contributing factors in young
      working Malaysian women in an urban setting. METHODS: The survey was conducted on
      a group of working women (age range 21-40 years) selected using convenience
      sampling. Data on foot problems was collected through an investigator-directed
      questionnaire and during clinical inspection of the foot. RESULTS: A total of 400
      women, with a mean age of 29.4 years, were recruited. Half (n = 200) of the women
      had experienced recurrent nontraumatic foot pain in the past one year. Subjective
      assessments of foot pain using the Numeric Intensity Scale gave an average score
      of 4.89 +/- 1.78 (range 2-10), with most episodes occurring at the heel. There
      was no statistically significant association between foot pain and age, ethnicity
      or body mass index. However, there was a higher incidence of foot pain in women
      wearing high-heeled footwear than those wearing non-high-heeled footwear (p =
      0.027, odds ratio 1.591). CONCLUSION: Nontraumatic foot pain is common among
      young working women in our society. More than half (68.4%) of the women with foot
      pain in our study attributed the pain to footwear. Wearing high-heeled shoes to
      work was a significant contributing factor. Increased public awareness on the
      importance of proper footwear may help to reduce the prevalence of nontraumatic
      foot pain in working women.

PMID- 24276100
TI  - Can the characteristics of emergency department attendances predict poor hospital
      outcomes in patients with sepsis?
AB  - INTRODUCTION: The emergency department (ED) is often the initial site of
      identification of patients with sepsis. We aimed to determine the characteristics
      of ED attendances that predict poor hospital outcomes. METHODS: We conducted a
      retrospective cohort study of adult patients in eight metropolitan EDs in Perth,
      Western Australia, from 2001 to 2006. Patients diagnosed with sepsis in the ED
      were identified using the International Classification of Diseases, 10th Revision
      Australian Modification code in the Emergency Department Information System
      (EDIS) database. The EDIS database was subsequently linked to mortality and
      hospital morbidity records. The following characteristics were examined: triage
      category, mode of arrival, source of referral and hospital of presentation.
      Multivariate logistic regression was performed to identify predictors of hospital
      mortality, prolonged length of stay, and admission to the intensive care unit
      (ICU). RESULTS: In the 1,311 patients diagnosed with sepsis in the ED, the
      hospital mortality and ICU admission rates were 19.5% and 18.5%, respectively.
      The mean hospital length of stay was 12 +/- 15 days. Acute triage categories
      predicted both hospital mortality and ICU admissions, while mode of arrival by
      ambulance was a predictor of all poor hospital outcomes (p < 0.001). Patients who
      presented to non-teaching hospitals had similar hospital outcomes as patients who
      presented to teaching hospitals. The source of referrals was not a predictor of
      poor hospital outcomes (p > 0.05). CONCLUSION: Mode of arrival and triage score,
      which are characteristics unique to the ED, may predict poor hospital outcomes in
      patients with sepsis.

PMID- 24276101
TI  - Toy safety in Singapore: where are we now?
AB  - INTRODUCTION: Toy-related injuries, a common reason for emergency department
      visits in the paediatric population, constitute a significant health burden in
      Singapore. Although government regulations imposed on toys and childcare-related
      items are in place, parents and caregivers still play a pivotal role in ensuring
      toy safety in children. We hypothesised that deficiencies in knowledge
      surrounding toy safety issues exist in our adult population. METHODS: We
      conducted a cross-sectional questionnaire study at KK Women's and Children's
      Hospital, Singapore, to examine the current attitudes, knowledge and practices of
      the local population regarding toy safety. Hypothetical questions on toy
      selection were included in the questionnaire to assess respondents' ability to
      identify appropriate toys and discern potentially dangerous toys for a specified
      age group. RESULTS: The scores of the 93 respondents showed that they were less
      able to identify appropriate toys for children in the 1-2 years (66.7%; 95%
      confidence interval [CI] 61.4%-72.0%) and 2-3 years age groups (69.9%; 95% CI
      65.5%-74.3%) than for children in the 0-1 year (82.8%; 95% CI 79.9%-85.7%) and 3
      5 years age groups (85.2%; 95% CI 81.2%-89.2%). Our survey also identified key
      areas for improvement (e.g. educational efforts and government regulation) in
      current practices in order to attain a higher level of toy safety. CONCLUSION:
      Our study highlights the current knowledge deficit in toy safety issues and the
      need for improvements in regulation, education and surveillance in order to
      minimise the risk of toy-related injuries in children.

PMID- 24276102
TI  - Evaluation of a novel device that maintains the balance of a cardiopulmonary
      resuscitation performer in a moving ambulance to improve chest compression
      quality.
AB  - INTRODUCTION: According to the findings of some studies, instability due to
      inertia during changes in speed may negatively impact the quality of chest
      compressions performed during cardiopulmonary resuscitation (CPR) in a moving
      environment. This study thus aimed to introduce a simple device that maintains
      the balance of a person performing CPR in a moving environment, such as an
      ambulance. We also sought to evaluate the effectiveness of this device in the
      improvement of the quality of chest compressions. METHODS: The experiment
      comprised a total of 40 simulated cardiopulmonary arrest scenes (20 in the
      experimental group and 20 in the control), in which CPR was conducted by eight
      paramedics. Each simulation involved two paramedics randomly selected from the
      eight. The ambulance took the same route from the simulated site to the hospital,
      and continuous CPR was performed on a manikin in the ambulance with or without
      the aid of our proposed novel device. RESULTS: The average number of chest
      compressions per simulation in the experimental and control groups was 1330.75
      and 1266.60, respectively (p = 0.095). The percentage of chest compressions with
      adequate depth achieved in the experimental and control groups was 72% +/- 4% and
      50% +/- 3%, respectively (p < 0.0001). CONCLUSION: By maintaining the balance of
      the CPR performer, our proposed novel device can offset the negative impact that
      instability (due to a moving environment) has on chest compressions. The device
      may also lead to an increase in the percentage of chest compressions that achieve
      adequate depth.

PMID- 24276103
TI  - Comparison of the effectiveness of intravenous piracetam and intravenous
      dimenhydrinate in the treatment of acute peripheral vertigo in the emergency
      department.
AB  - INTRODUCTION: We aimed to compare the effectiveness of intravenous piracetam with
      that of intravenous dimenhydrinate in the treatment of acute peripheral vertigo
      in the emergency department. METHODS: This double-blind study comprised a total
      of 200 patients, aged between 18 and 70 years, who had presented to the emergency
      department of Ankara Training and Research Hospital and were diagnosed with
      peripheral vertigo. Evaluation of the severity of the patients' vertigo was
      performed using a visual analogue scale, before and after drug administration.
      RESULTS: Both drugs were found to be effective (p < 0.001) and had comparable
      effects (p < 0.474). Dimenhydrinate was also found to have about two times the
      side effects of piracetam. Drowsiness was found to be the most common side effect
      of these two drugs. CONCLUSION: Dimenhydrinate and piracetam have similar levels
      of effectiveness with regard to acute vertigo. We conclude that piracetam, which
      has fewer side effects than dimenhydrinate, better vestibular compensation, and
      is effective for both acute and chronic vertigo, could be more frequently used in
      the emergency treatment of acute vertigo.

PMID- 24276104
TI  - A geographic information system-based analysis of ambulance station coverage area
      in Samsun, Turkey.
AB  - INTRODUCTION: The location of ambulance stations are of great importance, as
      location is a determining factor of whether ambulances are able to respond to
      emergency calls within the critical period. The aim of the present study was to
      determine whether the ambulance stations in the provincial centre of Samsun,
      Turkey, were able to cover their entire operational area within 10 mins of
      receiving an emergency call. METHODS: This study was based on emergency calls
      received by the emergency medical services of the study area. Detailed address
      data from the calls was used to produce thematic maps using the geographic
      information system (GIS). Buffer analysis was used to determine the adequacy of
      the stations' locations in relation to the time taken to respond to the emergency
      calls. RESULTS: In the study area, there were a total of 11,506 emergency
      ambulance calls made in 2009, which revealed a call density of 0.7 calls per ha
      and 23.8 calls per 1,000 population. A total of 75.8% of the calls were made due
      to medical reasons, while 11.6% were related to traffic accidents. The GIS-based
      investigation revealed that the 10-min coverage areas for the four ambulance
      stations in the provincial centre of Samsun served 76.9% of the area and 97.9% of
      its population. Of the 10,380 calls for which detailed address data were
      available, 99.2% were within the stations' 10-min coverage areas. CONCLUSION:
      According to the buffer analysis, the ambulance stations in the provincial centre
      of Samsun are able to reach 97.9% of the population within the critical 10-min
      response time. This study demonstrates that GIS is an indispensable tool for
      processing and analysing spatial data, which can in turn aid decision-making in
      the field of geographical epidemiology and public health.

PMID- 24276105
TI  - Antenatally diagnosed congenital diaphragmatic hernia in Singapore: a five-year
      series.

PMID- 24276106
TI  - Alexis Carrel (1873-1944): pioneer of vascular surgery and organ transplantation.

PMID- 24276107
TI  - Ultrasonography-guided ilioinguinal-iliohypogastric nerve block for inguinal
      herniotomies in ex-premature neonates.
AB  - The ilioinguinal-iliohypogastric (IG-IH) nerve block provides effective opioid
      sparing analgesia for inguinal surgeries. The technique is especially useful in
      apnoea-prone premature neonates with sacral anomalies and coagulopathy. A recent
      retrospective review of 82 ex-premature neonates who underwent inguinal
      herniotomy at KK Women's and Children's Hospital, Singapore, reported a success
      rate of 89% for landmark-guided IG-IH blocks. All blocks in that study were
      performed by senior paediatric anaesthetists using the landmark-based technique,
      which relies on fascial clicks. The IG-IH block is expected to be technically
      more difficult in neonates. There is also a stronger need to ensure success in
      these patients in order to avoid the use of opioids and reduce the risk of
      postoperative apnoea. Ultrasonographic guidance has been reported to improve the
      success of IG-IH blocks in older children to up to 94%. Herein, we report a
      series of six ex-premature neonates in whom ultrasonography-guided IG-IH blocks
      were successfully performed using reduced volumes of local anaesthetics (mean
      volume 0.17 mL/kg) for inguinal herniotomy. 

PMID- 24276108
TI  - Minimal fat renal angiomyolipoma with central scar and stellate calcification
      mimicking a calyceal calculus.
AB  - Renal angiomyolipomas are benign neoplasms composed of varying amounts of adipose
      tissue, smooth muscles and blood vessels. They typically contain macroscopic fat,
      which is seen as negative attenuation on computed tomography. Calcification and
      scarring is rarely seen in renal angiomyolipomas. We report the case of a 40-year
      old man who was found to have a renal angiomyolipoma with a central stellate scar
      and focal calcification. The lesion was initially misdiagnosed as a calyceal
      calculus. 

PMID- 24276109
TI  - Pseudoarthrosis and fracture: interaction between severe vitamin D deficiency and
      primary hyperparathyroidism.
AB  - A young woman with severe vitamin D deficiency presented with proximal muscle
      weakness, fragility fracture and pseudoarthrosis. On evaluation, she was found to
      have hypercalcaemia, a single parathyroid adenoma and an undetectable 25
      hydroxyvitamin D level. She received parenteral cholecalciferol and subsequently
      underwent curative parathyroidectomy. Postoperatively, she had hungry bone
      syndrome, which she gradually recovered from with calcium and calcitriol
      replacement. Notably, her calcium levels were in the lower limit of normal range
      and associated with elevated alkaline phosphatase levels at postoperative Day 14.
      Follow-up for the next four years showed that the patient had remarkable
      symptomatic and radiological improvements. In this report, we discuss the
      pathophysiological interactions between vitamin D deficiency and associated
      primary hyperparathyroidism. 

PMID- 24276110
TI  - Intra-articular haemangioma of the knee in the skeletally immature.
AB  - Intra-articular haemangioma is a rare and uncommon condition that sometimes
      presents in infants. The lesion can be a diagnostic challenge, with misdiagnosis
      often leading to delayed diagnosis and treatment. It is essential to establish
      and treat the condition early, as intra-articular haemangioma can lead to
      destruction of the joint and secondary arthrosis. Herein, we report the case of a
      five-year-old boy who presented with intra-articular haemangioma and discuss the
      management of his condition. 

PMID- 24276111
TI  - Splenic artery pseudoaneurysm due to seatbelt injury in a glucose-6-phosphate
      dehydrogenase-deficient adult.
AB  - A 23-year-old man presented with abdominal pain after suffering blunt trauma
      caused by a seatbelt injury. His low platelet count of 137 * 10(9)/L was
      initially attributed to trauma and his underlying hypersplenism due to glucose-6
      phosphate dehydrogenase (G6PD) deficiency. Despite conservative management, his
      platelet count remained persistently reduced even after his haemoglobin and
      clotting abnormalities were stabilised. After a week, follow-up imaging revealed
      an incidental finding of a pseudoaneurysm (measuring 9 mm * 8 mm * 10 mm)
      adjacent to a splenic laceration. The pseudoaneurysm was successfully closed via
      transcatheter glue embolisation; 20% of the spleen was also embolised. A week
      later, the platelet count normalised, and the patient was subsequently
      discharged. This case highlights the pitfalls in the detection of a delayed
      occurrence of splenic artery pseudoaneurysm after blunt injury via routine
      delayed phase computed tomography. While splenomegaly in G6PD may be a
      predisposing factor for injury, a low platelet count should arouse suspicion of
      internal haemorrhage rather than hypersplenism.

PMID- 24276112
TI  - Coexistence of tuberous sclerosis complex and malignant melanoma.
AB  - Tuberous sclerosis complex (TSC) is a multisystem genetic disorder characterised
      by widespread hamartomas in organs such as the skin, brain, heart, lung, liver
      and kidney. Although associations of TSC with hamartomas, angiomyolipomas and
      fibromas have been reported, there has been no report of its association with
      malignant melanoma. Herein, we describe a 31-year-old man with malignant melanoma
      associated with TSC. The patient had a history of epilepsia, multiple
      hypomelanotic macules, periungual fibromas and multiple hepatic lesions.
      Malignant melanoma was diagnosed by hepatic biopsy. To the best of our knowledge,
      this is the first report of malignant melanoma coexisting with TSC in the
      literature. We also present and discuss the imaging findings, prognosis,
      underlying mechanisms and practical approaches in relation to the disease. 

PMID- 24276113
TI  - Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT)
      deficiency.
AB  - Guanidinoacetate methyltransferase (GAMT) deficiency causes brain creatine
      deficiency characterized by developmental delays, speech delay, seizures and
      autism-like behavior. Identification and therapy at birth because of a positive
      family history has prevented intellectual disability and seizures in all cases
      reported. The objective of this study was to develop a method to identify
      patients with GAMT deficiency from newborn screening blood spots. Creatine and
      guanidinoacetate were extracted from 10,000 deidentified blood spots using the
      same protocol routinely used for newborn screening and quantified by stable
      isotope dilution using deuterated creatine and guanidinoacetate as internal
      standards. Residual dried blood spots from three infants with GAMT deficiency
      were used to evaluate the sensitivity of the method. A second tier test using
      UPLC-MS/MS was performed to analyze samples with a concentration of
      guanidinoacetate >2.44 MUmol/L (99.5th centile of the normal population). Fifty
      four blood spots required second tier testing in addition to seven blood spots
      from three patients with GAMT deficiency retrospectively analyzed. With second
      tier testing, only the samples from GAMT deficiency patients had elevated
      concentration of guanidinoacetate. Our results show that GAMT deficiency can be
      identified in newborns using routine extraction methods. The cost of this
      additional screening is minimal, as it does not require additional
      instrumentation, procedure, or sample collection. The use of a second tier test
      can reduce the false positive rate to a minimum. Summary Brain creatine
      deficiency syndromes cause mental retardation that can be prevented if therapy is
      initiated early in life. This manuscript reports that infants with GAMT
      deficiency (one of the brain creatine deficiency syndromes) can be identified
      from elevated guanidinoacetate in newborn blood spots with virtually absent false
      positive results using a second tier test. 

PMID- 24276115
TI  - Tuning excited-state proton transfer dynamics of a 3-hydroxychromone dye in
      supramolecular complexes via host-guest steric compatibility.
AB  - The photophysics of 2-(2'-benzofuryl)-3-hydroxychromone (BFHC) is remarkably
      modulated in its complexes with macrocyclic hosts such as beta-cyclodextrin (beta
      CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and methyl-beta-cyclodextrin (M
      beta-CD). BFHC exhibits dual emission bands, attributable to excited normal (N*)
      and tautomer (T*) forms, where the latter originates from the former through an
      excited-state intramolecular proton transfer (ESIPT) reaction. Fluorescence
      lifetimes of the tautomer, along with the intensity ratio (IT*/IN*) of the dual
      emission bands, and the fluorescence quantum yield (Phi) of the dye, increase
      significantly in the order beta-CD < HP-beta-CD < M-beta-CD to indicate
      increasing hydrophobicity of the dye environment in the host CD cavity. In
      accordance with this increasing hydrophobicity of the dye environment, the ESIPT
      dynamics of BFHC becomes increasingly fast in the host cavity in the order beta
      CD < HP-beta-CD < M-beta-CD. Binding constant data and molecular modeling studies
      indicate that the increasing order of the faster ESIPT dynamics originates from
      an increasingly tight host-guest spatial fit, which causes increasingly strong
      dehydration of the BFHC dye. Steric compatibility in size and shape between the
      host cavity and the guest, which modulates the tightness of the host-guest
      spatial fit and hence the extent of hydration, is a key factor for tuning the
      proton transfer dynamics since water molecules perturb the ESIPT reaction and
      quench the fluorescence of BFHC. 

PMID- 24276114
TI  - Management of acute perianal sepsis in neutropenic patients with hematological
      malignancy.
AB  - In neutropenic patients with acute perianal sepsis in the setting of
      hematological malignancy, the classical clinical features of abscess formation
      are lacking. Additionally, the role of surgical intervention is not well
      established. In this review, we discuss the challenges and controversy regarding
      diagnosis and optimal management when clear surgical guidelines are absent. In
      the literature, there is great diversity in the surgical approach to these
      patients, which leads to a high percentage of diagnostic errors, risks of
      complications, and unnecessary interventions. We review the literature and assess
      whether surgical intervention produces better outcomes than a non-surgical
      approach. Studies published on perianal sepsis in neutropenic cancer patients
      were identified by searching PubMed using the following key words: "perianal
      sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological
      malignancy, cancer". No randomized or prospective studies on the management of
      acute perianal sepsis in hematological malignancies were found. The largest
      retrospective study and most comprehensive clinical data demonstrated that 42% of
      patients were treated successfully without surgical intervention and without
      morbidity or mortality related to treatment chosen. Small retrospective studies
      advocated surgical intervention, while the majority of successes were in a non
      operative treatment. It is difficult to formulate a conclusion given the small
      retrospective series on management of neutropenic patients with hematological
      malignancies. While there is no evidence mandating a routine surgical approach in
      this category of patients, non-surgical management including careful follow-up to
      determine whether the patient's condition is deteriorating or treatment has
      failed is an acceptable approach in selected patients without pathognomonic
      features of abscess. Comprehensive and well-designed prospective studies are
      needed to firmly establish the guidelines of treatment protocols.

PMID- 24276116
TI  - Idiopathic chondrolysis of the hip: presentation, natural history and treatment
      options.
AB  - Idiopathic chondrolysis of the hip is a rare disorder characterized by pain,
      stiffness, limp and radiological loss of joint space of the affected hip. The
      clinical outcome varies from complete recovery to fibrous ankylosis. Management
      remains controversial. We aim to outline the natural history and pathology of the
      disease and treatment strategies. 

PMID- 24276117
TI  - Epicardial coronary artery spasm as cause of capecitabine-induced tako tsubo
      cardiomyopathy.

PMID- 24276118
TI  - Interactions of a Dopamine D1 Receptor Agonist with Glutamate NMDA Receptor
      Antagonists on the Volitional Consumption of Ethanol by the mHEP Rat.
AB  - Stimulation of the dopamine D1 receptor is reported to cause the phosphorylation
      of DARPP-32 at the thre34 position and activates the protein. If intracellular
      Ca2+ is increased, such as after activation of the glutamate NMDA receptor,
      calcineurin activity increases and the phosphates will be removed. This balance
      of phosphorylation control suggests that a D1 receptor agonist and a NMDA
      glutamate receptor antagonist should have additive or synergistic actions to
      increase activated DARPP-32 and consequent behavioral effects. This hypothesis
      was tested in a volitional consumption of ethanol model: the selectively bred
      Myers' high ethanol preferring (mHEP) rat. A 3-day baseline period was followed
      by 3-days of twice daily injections of drug(s) or vehicle(s) and then a 3-day
      post-treatment period. Vehicle, the D1 agonist SKF 38393, the non-competitive
      NMDA receptor antagonist memantine, or their combination were injected 2 h before
      and after lights out. The combination of 5.0 mg/kg SKF 38393 with either 3.0 or
      10 mg/kg memantine did not produce an additive or synergistic effect. For
      example, 5.0 mg/kg SKF reduced consumption of ethanol by 27.3% and 10 mg/kg
      memantine by 39.8%. When combined, consumption declined by 48.2% and the
      proportion of ethanol solution to total fluids consumed declined by 17%. However,
      the consumption of food also declined by 36.6%. The latter result indicates that
      this dose combination had a non-specific effect. The combination of SKF 38393
      with (+)-MK-801, another NMDA receptor antagonist, also failed to show an
      additive effect. The lack of additivity and specificity suggests that the
      hypothesis may not be correct for this in vivo model.  The interaction of these
      different receptor systems with intraneuronal signaling and behaviors needs to be
      studied further. 

PMID- 24276119
TI  - NMDA Receptor Antagonists for Treatment of Depression.
AB  - Depression is a psychiatric disorder that affects millions of people worldwide.
      Individuals battling this disorder commonly experience high rates of relapse,
      persistent residual symptoms, functional impairment, and diminished well-being.
      Medications have important utility in stabilizing moods and daily functions of
      many individuals. However, only one third of patients had considerable
      improvement with a standard antidepressant after 2 months and all patients had to
      deal with numerous side effects. The N-methyl-d-aspartate (NMDA) receptor family
      has received special attention because of its critical role in psychiatric
      disorders. Direct targeting of the NMDA receptor could result in more rapid
      antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists
      have been demonstrated in different animal models. MK-801 (a use-dependent
      channel blocker), and CGP 37849 (an NMDA receptor antagonist) have shown
      antidepressant properties in preclinical studies, either alone or combined with
      traditional antidepressants. A recent development is use of ketamine clinically
      for refractory depression. The purpose of this review is to examine and analyze
      current literature on the role of NMDA receptor antagonists for treatment of
      depression and whether this is a feasible route in drug discovery. 

PMID- 24276120
TI  - The Three Catecholics Benserazide, Catechol and Pyrogallol are GPR35 Agonists.
AB  - Nearly 1% of all clinically used drugs are catecholics, a family of catechol
      containing compounds. Using label-free dynamic mass redistribution and Tango beta
      arrestin translocation assays, we show that several catecholics, including
      benserazide, catechol, 3-methoxycatechol, pyrogallol, (+)-taxifolin and
      fenoldopam, display agonistic activity against GPR35. 

PMID- 24276121
TI  - Delivery of RNAi-Based Oligonucleotides by Electropermeabilization.
AB  - For more than a decade, understanding of RNA interference (RNAi) has been a
      growing field of interest. The potent gene silencing ability that small
      oligonucleotides have offers new perspectives for cancer therapeutics. One of the
      present limits is that many biological barriers exist for their efficient
      delivery into target cells or tissues. Electropermeabilization (EP) is one of the
      physical methods successfully used to transfer small oligonucleotides into cells
      or tissues. EP consists in the direct application of calibrated electric pulses
      to cells or tissues that transiently permeabilize the plasma membranes, allowing
      efficient in vitro and in vivo. cytoplasmic delivery of exogenous molecules. The
      present review reports on the type of therapeutic RNAi-based oligonucleotides
      that can be electrotransferred, the mechanism(s) of their electrotransfer and the
      technical settings for pre-clinical purposes. 

PMID- 24276122
TI  - Disease-causing allele-specific silencing by RNA interference.
AB  - Small double-stranded RNAs (dsRNAs) of approximately 21-nucleotides in size,
      referred to as small interfering RNA (siRNA) duplexes, can induce sequence
      specific posttranscriptional gene silencing, or RNA interference (RNAi). Since
      chemically synthesized siRNA duplexes were found to induce RNAi in mammalian
      cells, RNAi has become a powerful reverse genetic tool for suppressing the
      expression of a gene of interest in mammals, including human, and its application
      has been expanding to various fields. Recent studies further suggest that
      synthetic siRNA duplexes have the potential for specifically inhibiting the
      expression of an allele of interest without suppressing the expression of other
      alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene
      silencing by RNAi is an advanced technique with very promising applications. In
      this review, I would like to discuss the potential utility of allele-specific
      silencing by RNAi as a therapeutic method for dominantly inherited diseases, and
      describe possible improvements in siRNA duplexes for enhancing their efficacy. 

PMID- 24276123
TI  - Toxicity Studies on Novel N-Substituted Bicyclo-Heptan-2-Amines at NMDA
      Receptors.
AB  - Several novel norcamphor derivatives were designed and synthesized as
      uncompetitive NMDA receptor antagonists at the phencyclidine (PCP) binding site.
      Such compounds have potential as ligands for understanding and possibly the
      treatment of several neurodegenerative disorders and other glutamate-dependent
      disorders. We examined the toxic effects of the compounds as compared with
      memantine, an NMDA receptor antagonist that is FDA approved for treatment of
      Alzheimer's disease, by testing these compounds on two cell lines: MDCK (to mimic
      blood brain barrier) and N2a (a neuronal cell line). The compounds showed
      toxicity profiles similar to those of memantine i.e., dose dependence above 100
      MUM and IC50 values above 150 MUM for each cell line. It is known that the serum
      level of memantine under therapeutic conditions in patients is about 1 uM,
      indicting these compounds could have acceptable therapeutic indexes. 2-Phenyl-N
      (2-(piperidin-1-yl) ethyl)bicyclo[2.2.1]heptan-2-amine (5a) was found to possess
      acceptable toxicity profiles in both cell lines. Interestingly, this was the
      compound identified as a good lead in our previous studies based on binding and
      anticonvulsant (MES) activity studies. It has thus emerged as an excellent lead
      compound for further studies. 

PMID- 24276124
TI  - An allosteric modulator of the adenosine A1 receptor improves cardiac function
      following ischaemia in murine isolated hearts.
AB  - The effect of an allosteric modulator of the adenosine A1 receptors was
      investigated using an ischaemia-reperfusion protocol in murine isolated hearts.
      Isolated hearts were perfused with Kreb-Henseleit solution gassed with carbogen
      gas (95% O2 and 5% CO2) in Langendorff mode and electrically paced at 480 bpm.
      Following 20 min equilibration and 20 min global normothermic ischaemia, the
      allosteric modulator VCP333 (1 MUM) or the adenosine A1 receptor partial agonist
      VCP102 (10 MUM) were infused after 5 min of reperfusion for 15 min. Upon
      termination of the drug treatment, reperfusion continued for a further 40 min. At
      the end of 60 min reperfusion, treatment with VCP333 or VCP102 improved the
      recovery of the left ventricular developed pressure when compared to control
      group responses (p < 0.05). Neither compound affected end diastolic pressure,
      coronary flow rates or dP/dtmax values when compared to control tissues during
      reperfusion (p > 0.05). The infusion of VCP102 or VCP333 during reperfusion
      reduced cardiac troponin I efflux to 6.7% and 25% respectively of control heart
      efflux (p < 0.05). This data indicates that the allosteric modulator of the
      adenosine A1 receptor (VCP333) has similar characteristics to the adenosine
      receptor partial agonist VCP102 as it improves cardiac function and reduces
      myocardial cell death following an ischaemic episode. 

PMID- 24276126
TI  - Biological suppression of nitrification by selected cultivars ofHelianthus annum
      L.
AB  - The allelopathic potential of different cultivars ofHelianthus annuus against
      nitrification was studied using the soil incubation method. The results indicated
      that aqueous extracts and residues of roots and shoots of all test cultivars
      significantly reduced the nitrification rate in soil. However, cultivars Local
      and Citosol were found to be more inhibitory to nitrification than others. 

PMID- 24276127
TI  - Geranium defensive agents. III. Structural determination and biosynthetic
      considerations of anacardic acids of geranium.
AB  - Ozonolysis, dithioether derivatization, and EI and CI mass spectrometry were used
      to establish the location of the double bond in the side chain of the two major
      anacardic acids in geranium (Pelargonium hortorum) trichome exudate. The point of
      unsaturation was shown to be between C-5 and C-6 counting from the methyl end of
      the side chain, contradicting the earlier hypothesis that the olefmic bond was
      probably at the 9-10 position based upon expected biosynthetic considerations.
      The two major components are thus 6-[(Z)-10'-pentadecenyl]salicylic acid
      (C22H34O3) and 6-[(Z)-12'-heptadecenyl] salicylic acid (C24H38O3). This may
      indicate that the precursor of these anacardic acids is a saturated fatty acid
      since the location of a double bond at the 5-6 position is unusual among the
      unsaturated fatty acids. Capillary GLC and HPLC of the trichome exudate indicated
      the presence of small amounts of other anacardic acid analogs possessing such
      features as odd numbers of carbon atoms and saturated side chains. 

PMID- 24276125
TI  - Biologics in dermatology.
AB  - Skin and subcutaneous diseases affect millions of people worldwide, causing
      significant morbidity. Biologics are becoming increasingly useful for the
      treatment of many skin diseases, particularly as alternatives for patients who
      have failed to tolerate or respond to conventional systemic therapies. Biological
      therapies provide a targeted approach to treatment through interaction with
      specific components of the underlying immune and inflammatory disease processes.
      This review article examines the increasing evidence base for biologics in
      dermatology, including well-established treatments and novel agents. 

PMID- 24276128
TI  - Enniatins fromFusarium avenaceum isolated from balsam fir foliage and their
      toxicity to spruce budworm larvae,Choristoneura fumiferana (Clem.) (Lepidoptera:
      Tortricidae).
AB  - Material extracted from hyphae ofFusarium avenaceum, isolated from foliage of
      balsam fir,Abies balsamea, was toxic to spruce budworm larvae when incorporated
      into insect diet. The major insecticidal component of the toxic fraction was
      identified by chemical and spectroscopic methods as enniatin complex, rich in
      enniatin A/A1. Possible ecological implications of these observations are
      considered. 

PMID- 24276129
TI  - Allelochemical resistance of bald cypress,Taxodium distichum, heartwood to the
      subterranean termite,Coptotermes formosanus.
AB  - The heartwood of bald cypress,Taxodium distichum (L.) Rich., resisted feeding
      attack by the Formosan subterranean termite,Coptotermes formosanus Shiraki.
      Hexane-extracted heartwood, however, was consumed at > 12 times the amount of
      sound heartwood eaten. A bioassay usingT. distichum sapwood as a feeding
      substrate was employed to assess the antitermitic activity of successive hexane,
      acetone, and methanol extracts of heartwood shavings and isolates derived from
      the active hexane extract. Two fractions, eluted from the crude hexane extract by
      liquid chromatography, significantly reduced termite feeding compared to the
      parent extract, while a third fraction was less active than the original hexane
      extract. Each fraction contained one major component. All three components were
      structurally related diterpenes. The two most active heartwood constituents were
      identified by GC-MS and NMR as ferruginol and manool, while the third and least
      active, but most prevalent, compound in heartwood was identified as nezukol.
      Results of bioassays suggest that these allelochemicals act principally as
      feeding deterrents with accompanying termite mortality due to starvation. 

PMID- 24276130
TI  - Host-plant acceptance by geographic populations of the colorado potato
      beetle,Leptinotarsa decemlineata : Role of solanaceous alkaloids as sensory
      deterrents.
AB  - We used a detailed analysis of feeding behavior to investigate the role of
      solanaceous alkaloids as sensory-based feeding deterrents for the Colorado potato
      beetle,Leptinotarsa decemlineata (Say). Experiments were conducted on three
      geographic, host-adapted populations of beetles to determine whether evolutionary
      changes in host use have been accompanied by behavioral adaptations to alkaloids.
      Solanine and tomatine, steroidal glycoalkaloids found in two regional host
      plants, did not reduce leaf consumption or significantly alter behavior patterns
      of newly emerged beetles, including those from populations that normally will not
      feed on plants containing the compounds. Atropine, a tropane alkaloid found in
      several taxonomically related nonhost species, caused a significant increase in
      sampling behavior (indicating direct action on the sensory system) and reduced
      acceptance of treated potato leaves. We propose that variable acceptance of host
      plants among regional populations ofL. decemlineata has evolved independently of
      adaptations to alkaloids at the sensory level. To establish that secondary
      compounds such as atropine influence host choice in nature, field observations
      are needed to confirm that beetles routinely encounter, and sample, nonhost
      species. 

PMID- 24276131
TI  - Strawberry foliage headspace vapor components at periods of susceptibility and
      resistance toTetranychus urticae Koch.
AB  - Headspace components from strawberry foliage have been isolated by nitrogen
      entrainment and Tenax trapping. Traps were eluted with hexane, and components
      were analyzed by gas chromatography-mass spectrometry. Fifteen compounds were
      identified by comparison with authentic standards,trans-2-hexenal, 1
      hexanol,trans-2-hexen-1-ol,cis-3-hexen-1-ol, hexyl acetate,cis-3-hexenyl acetate,
      6-methyl-5-hepten-2-ol, 1-octanol, 1-octen-3-ol, linalool, alpha-terpineol,
      methyl salicylate, ethyl saiicylate, benzyl alcohol, and 2-phenylethanol. The
      relative amounts of these components were compared at flowering and after fruit
      harvest when plants were more resistant to the two-spotted spider
      mite,Tetranychus urticae Koch. The predominant components,cis-3-hexen-1-ol and
      its acetate, did not change markedly between the sampling periods, but methyl
      salicylate increased approximately 10-fold after fruit harvest. Methyl salicylate
      at low concentrations under bioassay conditions did not affect mite behavior. The
      biosynthetic relationship of this compound to other phenols which have been
      implicated in plant resistance is discussed. 

PMID- 24276132
TI  - Responses of male codling moths (Laspeyresia pomonella) to codlemone and other
      alcohols in a wind tunnel.
AB  - The primary pheromone (E,E)-8,10-dodecadien-1-ol (I, codle-mone), 11 further
      alcohols, and binary blends of both were evaluated for attractiveness as defined
      by the percentage ofL. pomonella males showing oriented upwind flight terminated
      by landing at the source within 10 min after release. Sources of I were
      attractive from 10(-5) MUg to 10(1) MUg, with approx. 70% males responding at 10(
      3)-10(-1) MUg. Most other alcohols also showed attractiveness, but the dose
      response curves differed greatly with respect to the range of effective lure
      doses as well as the maximum response level reached at any dose. (E,E)-7,9
      Undecadien-1-ol (III) revealed a dose-response curve similar in shape to I but
      shifted towards higher concentrations. (E,E)-8,10-Tridecadien-1-ol (II) and (E)
      8,10-undecadien-1-ol (IV) exhibited threshold values of 10(-5) MUg (same as for
      I) and were effective over, respectively, seven and nine decades of source load,
      but they did not reach a response level of 40% at any test amount. (E)-9,11
      Dodecadien-1-ol (VI) and the monoenes (E)-8-, (E)-10-, and (Z)-10-dodecen-1-ol
      (VIII-X) showed weak attractivity restricted to one to three test doses. Upwind
      approaches that broke off a few centimeters from the source were rarely seen in
      tests with I but frequently occurred with some of the analogs. When combined with
      10(-3) MUg of I, all alcohol analogs showed "inhibitory" properties, although the
      amounts required to obtain a significant lowering of response differed by up to
      10(5)-fold. This amount was the lowest (10(-4) MUg) for the positional isomer VI,
      and the highest (10(1) MUg) for undecan-1-ol (XI) and dodecan-1-ol (XII). With
      some mixtures, the presence of the inhibitor appeared to cause an alteration in
      landing behavior. No synergistic effects were seen in these tests. The results
      are briefly considered with respect to the sensory perception of the test stimuli
      and the involvement of minor components in the female pheromone blend. 

PMID- 24276133
TI  - Chemical trail marking and following by caterpillars ofMalacosoma neustria.
AB  - Chemical trail marking and following by gregarious caterpillars,Malacosoma
      neustria L. (Lepidoptera: Lasiocampidae), was studied in the laboratory. As in
      other species ofMalacosoma, larvae deposit a trail pheromone from a sternal
      secretory site when searching the host for food. Larvae in the vanguard of
      foraging columns establish chemical trails as they explore new territory. Marking
      behavior diminishes as successive unfed foragers utilize the trail. These
      exploratory trails are subsequently overmarked by fed larvae returning to the
      tent. Other foragers follow the trails of fed larvae in preference to trails of
      unfed larvae. Thus, like the eastern tent caterpillar,M. americanum, successful
      foragers ofM. neustria recruit colony-mates to feeding sites. The chemical
      activity of both recruitment and exploratory trails degrades slowly, suggesting
      that the trail pheromone ofM. neustria is a nonvolatile substance. Caterpillars
      ofM. neustria readily follow the nonvolatile trail pheromone which has been
      identified fromM. americanum, 5beta-cholestane-3,24-dione. 

PMID- 24276134
TI  - Isolation of the trail recruitment pheromone ofSolenopsis invicta.
AB  - TheSolenopsis invicta trail pheromone is synthesized by the Dufour's gland and is
      released through the sting apparatus. The recruitment subcategory of theS.
      invicta trail pheromone was shown to be composed of a mixture of the orientation
      pheromone, (Z,E)-alpha-farnesene and an unidentified homosesquiterpene consisting
      of three rings and one double bond (C-1). C-1 is present in worker Dufour's
      glands at only 75 pg per worker equivalent. This is the first report that
      demonstrates that different exocrine products from the same gland control
      different subcategories of behavior related to mass recruitment. 

PMID- 24276135
TI  - Effects of cotton leaf surface alkalinity on feeding ofSpodoptera littoralis
      larvae.
AB  - The high leaf surface pH in cotton (Gossypium hirsutum) var. Acala SJ2 was
      bioassayed againstSpodoptera littoralis larvae. Weight gain and leaf consumption
      of the larvae feeding on leaves devoid of alkalinity, due to daily washing, were
      recorded. Untreated cotton, with a leaf surface pH of 9.5-10.0 was used as
      control. The gland exudates contained potassium and magnesium cations, and the
      gland surface and intergland leaf areas were rich in calcium and phosphorus and
      low in K or Mg. The role of this plant antibiosis in the insect-host-plant
      relationship is discussed. 

PMID- 24276136
TI  - Effects of three phenolic compounds onLemna gibba G3.
AB  - Lemna gibba L. G3, (duckweed) was used as a bioassay organism to test the
      allelochemical effects of salicylic acid (SA), ferulic acid (FA), and
      umbelliferone (UM). Growth rate (K), dry weight (DW) and total chlorophyll (CHL)
      production were measured after seven days of growth. The bioassay procedure used
      50 ml of E medium with and without sucrose in 125-ml Erlenmeyer flasks plus the
      selected concentration of allelochemical. At concentrations of 50 MUM and
      greater, SA caused inhibition of K and DW production inL. gibba G3, while the
      threshold for CHL reduction was 20 MUM. FA inhibited the DW and CHL production at
      100 MUM when the compound was auto-claved in E medium containing sucrose.
      Treatments of UM were least toxic with an inhibition threshold of 500 MUM for K
      and DW production in medium without sucrose. UM did not reduce CHL production
      until 750 MUM. In some cases, different thresholds of inhibition were observed
      depending on the presence or absence of sucrose and tartaric acid in the medium,
      and whether or not the chemicals were autoclaved with the medium. 

PMID- 24276137
TI  - Comparison of earthworm- and fish-derived chemicals eliciting prey attack by
      garter snakes (Thamnophis).
AB  - Materials eliciting increased tongue flicking and prey attack in garter snakes
      were isolated from both earthworm and fish prey. New extraction methods based on
      chloroform-methanol mixtures are valuable adjuncts to the more typical aqueous
      preparations. Both high- and low-molecular weight components from earthworms and
      fish were active. The similarity between the active chemicals in these two
      classes of prey was established using several methods of analysis. These included
      chromatography, carbohydrate and amino acid analyses, and nuclear magnetic
      resonance. 

PMID- 24276138
TI  - Responses of braconid parasitoidsMicroplitis croceipes (Cresson) andM. demolitor
      Wilkinson to stereoisomers of kairomone 13-methylhentriacontane.
AB  - The responses ofMicroplitis croceipes (Cresson) andMicroplitis demolitor
      Wilkinson to theR andS stereoisomers of the kairomone 13-meth-ylhentriacontane
      were evaluated. Singly and in combination at 5, 50-, and 500-ng dosage levels
      each were tested. There was a linear dosage response by both species to the three
      dosages. Furthermore, there was no difference between responses to the two
      stereoisomers or their combination by either species at any dosage level. The
      effects of the two stereoisomers were fully interchangeable and additive. This is
      the first report of parasitoid responses to stereoisomers of a kairomone. 

PMID- 24276139
TI  - Synergistic interaction between potato glycoalkaloidsalpha-solanine andalpha
      chaconine in relation to destabilization of cell membranes: Ecological
      implications.
AB  - In studies of the lysis of rabbit erythrocytes, red beet cells, andPenicillium
      notatum protoplasts by the potato glycoalkaloids alpha-solanine and alpha
      chaconine, the latter was consistently the more membrane-disruptive compound and
      erythrocytes the more susceptible cell type. A 1?1 mixture of solanine and
      chaconine produced pronounced synergistic effects in all three test systems. In
      beet cells, such effects were apparent from an early stage of treatment and
      persisted over a period of several hours. With erythrocytes and fungal
      protoplasts, the synergism was maximal with mixtures containing approximately 70%
      chaconine, whereas with beet cells it peaked at approximately 40% chaconine.
      Synergistic interactions between solanine and chaconine also occurred with regard
      to cholesterol binding in vitro, with a maximum response corresponding to the 50%
      mixture. The implications of these findings for the nature and efficacy of
      chemical defense systems in plants are discussed. 

PMID- 24276140
TI  - Sex pheromone biosynthesis of (E,E)-8,10-dodecadienol in codling mothCydia
      pomonella involvesE9 desaturation.
AB  - Sex pheromone biosynthesis in the codling mothCydia pomonella (Lepidoptera;
      Tortricidae) was studied by topical application of deuterated fatty acids in DMSO
      to pheromone glands. The incorporation of deuterium label into fatty acids and
      alcohols in the pheromone gland was monitored by gas chromatography with flame
      ionization detection and mass spectrometry in the selected ion monitoring mode.
      Dodecanol, (E)-9-dodecenol, (E,E)-8,10-dodecadienol, tetradecanol, and
      hexadecanol were found in gland extracts. The application of [12,12,12
      (2)H3]dodecanoic acid resulted in labeled dodecanol, (E)-9-dodecenol, and (E,E)
      8,10-dodecadienol, as well as the corresponding labeled acids. No label was
      incorporated into tetradecanol or hexadecanol or any acid with more than 12
      carbon atoms. The application of labeled tetradecanoic or hexadecanoic acid
      introduced label not only into the 12-carbon alcohols, but also into
      tetradecanol, or tetradecanol and hexadecanol, respectively. The application of
      (E)-[11, 11,12,12,12,-(2)H5]9-dodecen-oic acid, whose facile synthesis is
      described, resulted in labeled (E)-9-do-decenol and (E,E)-8,10-dodecadienol. The
      (E,E)-8,10-dodecadienol so produced was characterized by an ion atm/z 186,
      equivalent to [M](+) of a dienol labeled with four deuterons. Thus, one deuterium
      label is lost when the labeled (E)-9-monoene is converted to the (E,E)-8,10
      diene. We conclude that (E,E)-8,10-dodecadienol is synthesized by chain
      shortening (beta-oxidation) of palmitic acid to dodecanoic acid, followed by an
      unusualE9 desaturation and subsequent conversion of this intermediate into the
      conjugated precursor, which is finally reduced to the pheromone alcohol. The
      evolutionary significance ofE9 desaturation being responsible for pheromone
      production in an Olethreutinae species is discussed. 

PMID- 24276141
TI  - Iridoid glycosides as oviposition stimulants for the buckeye butterfly,Junonia
      coenia (Nymphalidae).
AB  - Females ofJunonia coenia (Nymphalidae), a specialist on plants that contain
      iridoid glycosides, were found to use aucubin and catalpol, iridoid glycosides
      typical of a host plant,Plantago lanceolata (Plantaginaceae), as oviposition
      cues. Incorporating dried ground leaf material or pure iridoid glycosides into
      agar disks proved to be a very effective method of testing. In no-choice tests
      and choice tests, females laid more eggs on disks withP. lanceolata leaf material
      or iridoid glycosides, compared to agar controls. There was variation among
      individual females in preference for disks withP. lanceolata leaf material versus
      disks with iridoid glycosides. Females given a choice of three different
      concentrations of iridoid glycoside (0.2, 0.5, 1.0%) in the agar disks and a
      control laid more eggs on the disk with the highest concentration of iridoid
      glycoside. 

PMID- 24276142
TI  - Components of female sex pheromone of spotted bollworm,Earias vittella F.
      (Lepidoptera: Noctuidae): Identification and field evaluation in Pakistan.
AB  - Ovipositor washings from virgin femaleEarias vittella (F.) (Lepidoptera:
      Noctuidae) moths were examined by gas chromatography (GC) linked to
      electroantennography (EAG). Six components were detected by the male moth. These
      were identified by comparison of their retention times with those of a range of
      synthetic standards on fused silica capillary GC columns as hexadecanal, (Z)-11
      hexadecenal, (E,E)-10,12-hexadecadienal, octadecanal, (Z)-11-octadecenal, and
      (E,E)-10,12-hexadecadien-1-ol in 1?2?10?2?4?1 ratio. Field testing in Pakistan
      showed that a 2?10?2 mixture of (Z)-11-hexadecenal, (E,E)-10,12-hexadecadienal,
      and (Z)-11-octadecenal was as attractive to maleE. vittella moths as the six
      component mixture and equal in attractiveness to a virgin female moth. Omitting
      (Z)-11-hexadecenal or (Z)-11-octadecenal greatly reduced this attractiveness. It
      was found that synthetic lures must be protected from sunlight to prevent loss of
      attractiveness caused by isomerization of the conjugated diene aldehyde, and
      addition of (E,Z)-10,12-hexadecadienal, one of the products of isomerization, was
      shown to reduce attractiveness significantly. During this work, a 10?1 mixture of
      (E,E)-10, 12-hexadecadienal and (Z)-11-hexadecenal was shown to be as attractive
      toE. insulana (Boisd.) male moths as a virgin female moth, and the attractiveness
      of this mixture was further increased by addition of (E,Z)-10,12-hexadecadienal. 

PMID- 24276143
TI  - Identification of female sex pheromone in alfalfa blotch leafminer,Agromyza
      frontella (Rondani)(Diptera: Agromyzidae).
AB  - Gas chroinatography of hexane extracts of 3-day-old virgin A.frontella adults
      revealed a branched saturated hydrocarbon present only in females. This compound
      was isolated by argentation chromotography and preparative GC, identified by GC
      and GC-MS as 3,7-dimethylnonadecane, and subsequently synthesized. Three-day-old
      virgin females contained 54.1 +/- 3.5 ng (+/- SEM;N = 48) of 3,7
      dimethylnonadecane. Male cadavers do not elicit male courtship behavior, but when
      treated with ~ 18 ng of 3,7-dimethylnonadecane they were as attractive as
      cadavers of 3-day-old virgin females. Black cotton knots were less attractive
      than male cadavers when treated with 3,7-dimethylnonadecane, but all bioassays
      indicated that this compound is an important semiochemical modulating male mating
      behavior. 

PMID- 24276144
TI  - Synthesis of carrier-free tritium-labeled queen bee pheromone.
AB  - A short synthesis of [4,5-(3)H2] (E)-9-oxo-2-decenoic acid (ODA), a high-specific
      activity tritium-containing isotopomer of the queen bee pheromone, is described.
      Catalytic tritiation of the ketal of ethyl 9-oxo-4-decenoate introduces tritium
      into two positions, one of which is completely unactivated. Subsequent
      transformation by selenation, oxidation, and hydrolysis affords the labeled 9-ODA
      at >60 Ci/mmol. The material is suitable for biochemical studies of binding and
      catabolism in ovarian, antennal, and other target tissues. 

PMID- 24276145
TI  - Cuticular hydrocarbons of tsetse flies II:Glossina fuscipes fuscipes, G. palpalis
      palpalis, G. p. gambiensis, G. tachinoides, andG. brevipalpis.
AB  - The alkanes (methylalkanes) were analyzed from both sexes of four members of
      thepalpalis group of tsetse flies,Glossina fuscipes fuscipes, G. palpalis
      gambiensis, G. palpalis palpalis, G. tachinoides plus onefusca group member, G.
      brevipalpis, to determine structures, abundances, and the presence of unique or
      specific methylalkanes. These insects are unique in that trimethylalkanes were
      major components except in femaleG. tachinoides and both sexes ofG. brevipalpis
      where 2-methylalkanes were the major components. The identification of novel long
      chain tetramethylalkanes, including 11,15,19,23-tetramethylpentatriacontane, a
      minor component of femaleG. f. fuscipes, G. p. gambiensis, andG. p. palpalis, is
      reported here. Tetramethylalkanes were significant components of both sexes ofG.
      brevipalpis. The major tetramethylalkane in G.brevipalpis is 3,7,11,15
      tetramethylhen-triacontane. The use of the methylalkanes as taxonomic indicators
      in tsetse is discussed. 

PMID- 24276146
TI  - Toxicity and toxicokinetics of 6-methoxybenzoxazolinone (MBOA) in the european
      corn borer,Ostrinia nubilalis (Hubner).
AB  - The maize-derived secondary chemical 6-methyoxybenzoxazoii-none (MBOA) and a
      tritiated derivative were prepared synthetically for a detailed examination of
      their toxicity and toxicokinetics in the European corn borer (ECB),Ostrinia
      nubilalis. During feeding trials with MBOA incorporated into meridic diets (at 0,
      0.5, 1.5, 2.5, and 4.0 mg/g diet), the mean time to pupation and adult emergence
      was significantly lengthened at concentrations of 1.5 mg MBOA/g diet and above.
      Increased mortality occurred at concentrations at 1.5 mg/g and above. A decrease
      in the sex ratio (female/ total) and fecundity was observed at concentrations of
      0.5 mg/g and above. The latter observations represent new biological effects
      related to MBOA. In tracer studies, both uptake and excretion of MBOA
      administered in diets to larvae increased linearly with concentration. Body
      burden values indicated that the ECB larvae were capable of excreting enough
      compound to maintain total tissue levels at approximately 50% of the dietary
      concentration. Total amount of label increased with larval stage, but decreased
      in adults due to a large amount of label eliminated in the pupal case. In topical
      application studies, elimination of the label in the frass was rapid, reaching
      60% by 6 hr and 82% of applied dose by 24 hr. Accumulation of label in tissues
      other than hemolymph was small. The results show that MBOA is toxic to ECB, but
      the insect has efficient methods for minimizing these effects. 

PMID- 24276147
TI  - Haloacetate analogs of pheromones: Effects on catabolism and electrophysiology
      inPlutella xylostella.
AB  - A series of mono-, di-, and trihalogenated acetate analogs of Zl 1-16: Ac were
      prepared and examined for electrophysiological activity in antennae of males of
      the diamondback moth,Plutella xylostella. In addition, two potential affinity
      labels, a diazoacetate (Dza) and a trifluoromethyl ketone (Tfp), were evaluated
      for EAG activity. The Z11-16?Ac showed the highest activity in EAG assays,
      followed by the fluorinated acetates, but other halo-acetates were essentially
      inactive. The polar diazoacetate and the trifluoromethyl ketone were also very
      weak EAG stimulants. The effects of these analogs on the hydrolysis of [(3)H]Z11
      16?Ac to [(3)H]Z11-16?OH by antennal esterases was also examined. The three
      fluorinated acetates showed the greatest activity as inhibitors in competition
      assays, with rank order F2Ac > F(3)Ac > FAc > Ac > Cl2Ac > ClAc > Dza > Br2Ac >
      BrAc > Tfp > I > Cl3Ac > Br3Ac > OH. The relative polarities of the haloacetates,
      as determined by TLC mobility, are in the order mono- > di- > trihalo, but F, Cl,
      Br, and I all confer similar polarities within a substitution group. Thus, the
      steric size appears to be the predominant parameter affecting the interactions of
      the haloacetate analogs with both receptor and catabolic proteins inP. xylostella
      males. 

PMID- 24276148
TI  - Composition and role of volatile substances in atmosphere surrounding two
      gregarious locusts,Locusta migratoria andSchistocerca gregaria.
AB  - Volatile substances in the atmosphere surrounding gregarious locustsSchistocerca
      gregaria andLocusta migratoria were captured and investigated by combined gas
      chromatography-mass spectrometry. Three aromatic derivates have been identified:
      phenol, guaiacol, and veratrole. Their relative percentages differ for different
      ages and species. Behavioral tests show that essentially phenol, guaiacol, and
      the mixture of the three products tend to increase the aggregation behavior in
      both species and thus act as "cohesion pheromones." 

PMID- 24276149
TI  - Cuticular hydrocarbons of dampwood termites,Zootermopsis: Intra- and intercolony
      variation and potential as taxonomic characters.
AB  - Colonies ofZootermopsis were collected from the central Sierra Nevada and the
      Monterey Penninsula in California, and from southern Arizona. Cuticular
      hydrocarbons were identified by gas chromatography-mass spectrometry (GC-MS) and
      quantified by gas-liquid chromatography (GLC) for each caste of all colonies.
      Four consistent and distinct cuticular hydrocarbon patterns, or chemical
      phenotypes, were identified. Unique and abundant monomethyl- and dimethylalkanes,
      and ann-alkene provided easy separation of the various phenotypes. Significant
      differences in the proportions of the various components were found among castes
      within a colony and colonies within phenotypes from California. Differences in
      the hydrocarbon proportions for castes were not consistent between colonies. The
      current taxonomy of the genusZootermopsis recognizes three species. Our
      identification of four consistent, unique cuticular hydrocarbon phenotypes from
      the three described species should alert systematists and others to a major
      concern. If there are truly only three extant species, then the hypothesis that
      cuticular hydrocarbon profiles in this genus are species specific is not
      acceptable. Conversely, if cuticular hydrocarbon profiles are truly species
      specific, then there is at least one new, undescribed species ofZootermopsis. 

PMID- 24276150
TI  - CCN5 overexpression inhibits profibrotic phenotypes via the PI3K/Akt signaling
      pathway in lung fibroblasts isolated from patients with idiopathic pulmonary
      fibrosis and in an in vivo model of lung fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial
      lung disease with unknown etiology and undefined treatment modality. Fibroblasts
      are regarded as the major cell type that mediates the onset and progression of
      lung fibrosis by secreting large amounts of extracellular matrix (ECM) proteins,
      such as connective tissue growth factor (CTGF/CCN2). Current knowledge confers a
      crucial role of CCN2 in lung fibrosis. CCN5, another member of the CCN family,
      has been suggested to play an inhibitory role in some fibrotic diseases, such as
      cardiac fibrosis. However, the role of CCN5 in the process of IPF remains
      unknown. In the present study, using western blot analysis, we demonstrate that
      CCN2 is highly expressed in fibroblasts derived from IPF tissue, but is only
      slightly expressed in normal human lung fibroblasts. However, CCN5 was weakly
      expressed in all the above cells. qRT-PCR revealed that transforming growth
      factor (TGF)-beta1 stimulation increased CCN2 expression in the IPF-derived
      cultures of primary human lung fibroblasts (PIFs) in a time- and concentration
      dependent manner, but only slightly affected the expression of CCN5. The
      overexpression of CCN5 induced by the transfection of PIFs with recombinant
      plasmid did not affect cell viability, proliferation and apoptosis; however, it
      significantly suppressed the expression of CCN2, alpha-smooth muscle actin (alpha
      SMA) and collagen type I. The TGF-beta1-induced upregulation of the
      phosphorylation of Akt was reversed by CCN5 overexpression. Our results also
      demonstrated that adenovirus-mediated CCN5 overexpression in a mouse model of
      bleomycin-induced IPF significantly decreased the hydroxyproline content in the
      lungs, as well as TGF-beta1 expression in bronchoalveolar lavage fluid. Taken
      together, our data demonstrate that CCN5 exerts an inhibitory effect on the
      fibrotic phenotypes of pulmonary fibroblasts in vitro and in vivo, and as such
      may be a promising target for the treatment of IPF.

PMID- 24276151
TI  - Aging attenuates the association of central obesity with the accumulation of
      metabolic risk factors when assessed using the waist circumference measured at
      the umbilical level (the Japanese standard method).
AB  - OBJECTIVE: The objective of this study was to clarify the generation and gender
      differences in the association between central obesity and the accumulation of
      metabolic risk factors (RFs) in the Japanese population. MATERIAL AND METHODS: A
      total of 12 389 subjects (age: 18-80 years) without receiving medication for
      diabetes, dyslipidemia or hypertension were enrolled in this study and divided
      according to age and gender. In each group, we performed analyses as follows: (1)
      a receiver operating characteristic (ROC) analysis to evaluate the utility of the
      waist circumference (WC) for detecting subjects with multiple RFs of metabolic
      syndrome (MS); (2) a cross-sectional study to examine the relationship between
      the WC and the odds ratio (OR) for detecting those subjects and (3) a
      longitudinal study to examine how longitudinal changes (Delta) in WC over a 1
      year period affected the values of each metabolic RF. RESULTS: With age, the WC
      cutoff values yielding the maximum Youden index for detecting subjects with
      multiple RFs increased only in women, and the areas under the curves of the ROC
      analysis of WC for detecting those subjects decreased in both genders. The
      positive correlation between the WC and the OR for detecting subjects with
      multiple RFs became weaker with age, especially in women. In the longitudinal
      study, the significant correlation between DeltaWC and Delta each metabolic RF,
      except for hypertension, and between DeltaWC and Delta the number of RFs became
      weaker with age in women, whereas the significant correlation between DeltaWC and
      Delta the number of RFs was not affected with age in men. In women aged ?60
      years, none of the changes in each metabolic RF were significantly associated
      with DeltaWC. CONCLUSIONS: Aging attenuates the association of central obesity
      with the accumulation of metabolic RFs, especially in women.

PMID- 24276152
TI  - Embolic complications after endovascular repair of abdominal aortic aneurysms.
AB  - PURPOSE: This retrospective study aimed to review our experiences with
      endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs), along
      with the incidence, risk factors and prognoses of associated embolic events. Our
      goal was to present the EVAR results and related risk factors from a single
      center, with a focus on embolic complications. METHODS: We retrospectively
      reviewed the data of 539 patients with AAAs who underwent elective EVAR at Jikei
      University from July 2006 to April 2009. Of these, 438 patients were selected
      after excluding those requiring fenestrated and branched EVAR. RESULTS: The
      technical success rate was 91.1 % (399/438) with no surgical mortality. Embolic
      complications occurred in nine patients (2 %), four of whom developed ischemic
      colitis and were successfully treated with bowel rest and hydration. Lower
      extremity atheroembolization and stroke occurred in three and one patients,
      respectively. Two patients died of cholesterol crystal embolization. Seven of the
      nine embolic complications (77.8 %) were associated with the use of Zenith stent
      grafts. A Cox proportional-hazard regression analysis of the adjusted risk
      factors showed that smoking and severe arterial degeneration of the aorta,
      referred to as a shaggy aorta, to be independent predictors of embolic
      complications. CONCLUSIONS: The presence of a shaggy aorta and a history of
      smoking are independent predictors of embolic complications associated with EVAR.

PMID- 24276153
TI  - Visible-light-induced electron transfer between alternating stacked layers of
      tungstate and titanate mediated by excitation of intercalated dye molecules.
AB  - Visible-light-induced electron transfer from a tungstate to a titanate layer was
      demonstrated to be mediated by excited rhodamine B (RhB) intercalated by ion
      exchange between the two layers. The distance of only 1 nm between the layers
      provides a large contact area that enables the efficient mediation of electron
      transfer by RhB. 

PMID- 24276154
TI  - Changes in the activities of ferredoxin- and NADH-glutamate synthase during
      seedling development of peas.
AB  - Ferredoxin-glutamate synthase (EC 1.4.7.1) and NADH-glutamate synthase (EC
      1.4.1.14) activities in pea seedlings (Pisum sativum L., cv. Alaska) were
      measured during germination and the early stages of growth. Both enzymes were
      detected at all stages in the developing roots and shoots, but their relative
      activities varied according to the growth stages. In shoots of 5-d-old seedlings,
      the ratio of the NADH-enzyme to the ferredoxin-enzyme was 72:28. However, the
      ferredoxin-activity increased rapidly and in shoots of 17-d-old seedlings, the
      activities were in the ratio of 3:97. Similar trends in these ratio changes were
      observed in the roots. In both tissues, the NADH-enzyme was shown to be
      predominant in the immature parts. When chloroplasts prepared from mature pea
      leaves were incubated with [(14)C]glutamine and 2-oxoglutarate, the production of
      [(14)C]glutamate was found to be light dependent and was inhibited by azaserine
      (3 mM) and 3-(3,4-dichlorophenyl)-1-1-dimethylurea (20 MUM). In contrast,
      considerable amounts of [(14)C]glutamate were formed by chloroplasts from young
      leaves even in the dark. Addition of malate or dihydroxyacetone phosphate to the
      reaction mixture resulted in a twofold increase of this dark- and azaserine
      sensitive [(14)C]glutamate formation. 

PMID- 24276155
TI  - Superoxide, hydrogen peroxide, and the gelling of phloem sap from Cucurbita pepo.
AB  - The possible involvement of superoxide and hydrogen peroxide in the oxidative
      gelling of phloem exudate from Cucurbita pepo. was investigated. Neither
      superoxide dismutase (EC 1.15.1.1) nor catalase (EC 1.11.1.6) inhibited the
      reaction. Although catalase could not be detected in exudate, both peroxidase
      (EC. 1.11.1.7) and superoxide dismutase were present in reasonable amounts.
      Polyacrylamide gel electrophoresis revealed one major and one minor isozyme of
      superoxide dismutase, both of which were adjudged to contain copper and zinc as
      their prosthetic metals, on the basis of cyanide inhibition and molecular weight.

PMID- 24276156
TI  - Properties of phosphoenolpyruvate carboxylase in rapidly prepared, desalted leaf
      extracts of the Crassulacean acid metabolism plant Mesembryanthemum crystallinum
      L.
AB  - Properties of phosphoenolpyruvate (PEP) carboxylase, obtained from leaves of
      Mesembryanthemum crystallinum L. performing Crassulacean acid metabolism (CAM),
      were determined at frequent time points during a 12-h light/12-h dark cycle. Leaf
      extracts were rapidly desalted and PEP carboxylase activity as a function of PEP
      concentration, malate concentration, and pH was measured within 2 min after
      homogenization of the tissue. Maximum velocity of PEP carboxylase was similar in
      the light and dark at pH 7.5 and pH 8.0. However, PEP carboxylase had as much as
      a 12-fold lower K m for PEP and as much as a 20-fold higher K i for malate during
      the dark than during the light periods, the magnitude of these differences being
      dependent on the assay pH. Assuming that enzyme properties immediately after
      isolation reflect the approximate state of the enzyme in vivo, these differences
      in enzyme properties reduce the potential for CO2 fixation via PEP carboxylase in
      the light. A small decrease in cytoplasmic pH in the light would greatly magnify
      the above differences in day/night properties of PEP carboxylase, because the
      sensitivity of PEP carboxylase to inhibition by malate increased with decreasing
      pH. Properties of PEP carboxylase were also studied in plants exposed to short
      term perturbations of the normal 12-h light/12-h dark cycle (e.g., prolonged
      light period, prolonged dark period). Under all light/dark regimes, there was a
      close correlation between change in properties of PEP carboxylase and changes of
      the tissue from acidification to deacidification, and vice versa. Changes in
      properties of PEP carboxylase were not merely light/dark phenomena because they
      were also observed in plants exposed to continuous light or dark. the data
      indicate that, during CAM, PEP carboxylase exists in two stages which differ in
      their capacity for net malate synthesis. The "physiologically-active" state is
      distinguished by a low K m for PEP and a high K i for malate and favors malate
      synthesis. The "physiologically-inactive" state has a high K m for PEP and a low
      K i for malate and exists during periods of deacidification and other periods
      lacking synthesis of malic acid. 

PMID- 24276157
TI  - Activity and quantity of ribulose bisphosphate carboxylase-and
      phosphoenolpyruvate carboxylase-protein in two Crassulacean acid metabolism
      plants in relation to leaf age, nitrogen nutrition, and point in time during a
      day/night cycle.
AB  - Activity of ribulose 1,5-bisphosphate (RuBP) carboxylase in leaf extracts of the
      constitutive Crassulacean acid metabolism (CAM) plant Kalanchoe pinnata (Lam.)
      Pers. decreased with increasing leaf age, whereas the activity of
      phosphoenolpyruvate (PEP) carboxylase increased. Changes in enzyme activities
      were associated with changes in the amount of enzyme proteins as determined by
      immunochemical analysis, sucrose density gradient centrifugation, and SDS gel
      electrophoresis of leaf extracts. Young developing leaves of plants which
      received high amounts of NO 3 (-) during growth contained about 30% of the total
      soluble protein in the form of RuBP carboxylase; this value declined to about 17%
      in mature leaves. The level of PEP carboxylase in young leaves of plants at high
      NO 3 (-) was an estimated 1% of the total soluble protein and increased to
      approximately 10% in mature leaves, which showed maximum capacity for dark CO2
      fixation. The growth of plants at low levels of NO 3 (-) decreased the content of
      soluble protein per unit leaf area as well as the extractable activity and the
      percentage contribution of both RUBP carboxylase and PEP carboxylase to total
      soluble leaf protein. There was no definite change in the ratio of RuBP
      carboxylase to PEP carboxylase activity with a varying supply of NO 3 (-) during
      growth. It has been suggested (e.g., Planta 144, 143-151, 1978) that a rhythmic
      pattern of synthesis and degradation of PEP carboxylase protein is involved in
      the regulation of beta-carboxylation during a day/night cycle in CAM. No such
      changes in the quantity of PEP carboxylase protein were observed in the leaves of
      Kalanchoe pinnata (Lam.) Pers. or in the leaves of the inducible CAM plant
      Mesembryanthemum crystallinum L. 

PMID- 24276158
TI  - Water relations of immobilized giant algal cells.
AB  - Cells of Halicystis parvula, Acetabularia mediterranea, and Valonia utricularis
      were immobilized in a cross-linked alginate matrix (4-6% w/w) in order to
      simulate water-relation experiments in individual cells of higher plant tissues.
      The immobilization of these cells did not lead to an increase in the mechanical
      stability of the cell walls. This was demonstrated by measuring the volumetric
      elastic modulus of the cell wall and its dependence on turgor pressure with the
      aid of the non-miniaturized pressure probe. In immobilized cells, no changes in
      the absolute value of the elastic modulus of the cell wall could be detected for
      any given pressure. At the maximum turgor pressure at which non-immobilized cells
      normally burst (about 3-7 bar for V. utricularis; depending on cell size, 3 bar
      for A. mediterranea and 0.9 bar for H. parvula) reversible decreases in the
      pressure are observed which are succeeded by corresponding pressure increases.
      This obvervation indicates that coating the cells with the cross-linked matrix
      protects them from rapid water and turgor pressure loss. Turgor pressure
      relaxation processes in immobilized cells, which could be induced hydrostatically
      by means of the pressure probe, yielded accurate values for the half-times of
      water exchange and for the hydraulic conductivity of the cell membrane. The
      results demonstrate that the water transport equations derived for single cells
      in a large surrouding medium are valid for immobilized cells, so that any
      influence exerted by the unstirred layer which is caused by the presence of the
      cross-linked matrix can be ignored in the calculations. On the other hand, the
      evaluation of the half-times of water exchange and the hydraulic conductivity
      from turgor pressure relaxation processes, which have been induced osmotically,
      only yields correct values under certain circumstances. The model experiments
      presented here show, therefore, that the correct Lp-value for an individual cell
      in a higher plant tissue can probably only be obtained presently by using the
      pressure probe technique rather than the osmotic method. The results are also
      discussed in relation to the possible applications of immobilized cells and
      particularly of immobilized micro-organisms in catalytic reaction runs on an
      industrial scale. 

PMID- 24276159
TI  - Photoperiodism and crassulacean acid metabolism : I. Immunological and kinetic
      evidences for different patterns of phosphoenolpyruvate carboxylase isoforms in
      photoperiodically inducible and non-inducible Crassulacean acid metabolism
      plants.
AB  - Plants of Kalanchoe blossfeldiana v. Poelln. Tom Thumb and Sedum morganianum E.
      Walth. were grown under controlled photoperiodic conditions under either short or
      long days. Gaz exchange measurements confirmed that in K. blossfeldiana
      Crassulacean acid metabolism (CAM) was photoperiodically inducible and that S.
      morganianum performed CAM independently of photoperiod. With K. blossfeldiana, a
      comparison of catalytic and regulatory properties of phosphoenolpyruvate
      carboxylase (PEPC, EC 4.1.1.31) from short-day and long-day grown plants showed
      differences, but not with S. morganianum. Ouchterlony double diffusion tests and
      immunotitration experiments (using a S. morganianum PEPC antibody) established
      that CAM is induced in K. blossfeldiana-but not in S. morganianum-through the
      synthesis of a new PEPC isoform; this form shows an immunological behavior
      different from that prevailing under non-inductive conditions and can be
      considered as specific for CAM performance. 

PMID- 24276160
TI  - Photoperiodism and Crassulacean acid metabolism : II. Relations between leaf
      aging and photoperiod in Crassulacean acid metabolism induction.
AB  - Measurements of net CO2 exchange, malate accumulation, properties and capacity of
      phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) in leaves of different ages
      of two short-day dependent Crassulacean acid metabolism (CAM) plants (Kalanchoe
      blossfeldiana v. Poelln. Tom thumb and K. velutina Welw.) show that, in both
      species: a) young leaves from plants grown under long days display a CO2 exchange
      pattern typical of C3 plants; b) leaf aging promotes CAM under long-day
      conditions; c) short-day treatment induces CAM in young leaves to a higher degree
      than aging under long days; d) at least in K. blossfeldiana, the PEPC form
      developed with leaf aging under long days and the enzyme form synthetized de novo
      in young leaves grown under short days were shown to have similar properties.
      Short days also promote CAM in older leaves though at a lesser extent than in
      young leaves: The result is that this photoperiodic treatment increases the
      general level of CAM performance by the whole plant. The physiological meaning of
      the control of PEPC capacity by photoperiodism could be to afford a precisely
      timed seasonal increase in CAM potentiality, enabling the plant to immediately
      optimize its response to the onset of drought periods. 

PMID- 24276161
TI  - Photoperiodism and Crassulacean acid metabolism : III. Different characteristics
      of the photoperiod-sensitive and non-sensitive isoforms of phosphoenolpyruvate
      carboxylase and Crassulacean acid metabolism operation.
AB  - Sensitivity to glucose-6-P, inorganic phosphate and malate, Km
      phosphoenolpyruvate (PEP), and the effect of pH were comparatively investigated
      for phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) extracted along the day
      night cycle from leaves of Kalanchoe blossfeldiana v. Poelln. Tom Thumb, grown
      under different photoperiodic conditions. Under long days, sensitivity to
      effectors is weak and varies only slightly during the 24h cycle, together with
      small variations of Km (PEP), ranging from 1.2 to 1.8 mM. The response-curve to
      pH shows two peaks for pH 7.4 and 8.4. Transfer of the plants to short days
      established an increase in the sensitivity of the enzyme to the effectors
      together with the appearance of a day-night variation of this effect, maximum
      during the day. A clear diurnal oscillation of Km (PEP) is observed from 3.1 mM
      at the beginning of day (09.00 h) to 0.9 mM at midnight (00.00 h), at pH 7.4.
      These results complement previous electrophoretic and immunological data by
      affording enzyme kinetic evidence that short days induce a PEP carboxylase form
      responsible for full-Crassulacean acid metabolism (CAM) operation which is
      kinetically different from the photoperiod-sensitive, C3-like form prevailing in
      young leaves under long days. The results indicate that diurnal enzymic rhythms
      would improve the efficiency of the metabolic regulatory mechanisms and act as a
      coordinating factor for the daily and seasonal adaptive operation of CAM. 

PMID- 24276162
TI  - The proportion of calcium-bound pectin in plant cell walls.
AB  - The amount of pectin held in cell walls by ionic bonds only was determined by
      extraction with cyclohexanediamine tetraacetic acid (CDTA) at room temperature,
      to remove calcium ions without degrading the galacturonan chains. Enzymic
      degradation was avoided by extracting the cell walls with phenol-acetic acid
      water during preparation. From cell walls of celery petioles, cress hypocotyls
      and tomato and cucumber pericarp CDTA extracted 64-100 mg g(-1) pectin, leaving
      80-167 mg g(-1) uronic acid in the residue. An additional extraction at high
      ionic strength was used to make the galacturonan chains more flexible and thus
      detach any pectins held by steric interactions, but the amount released in this
      way was small. Most of the residual uronic acid polymers could be extracted by
      cold alkali and remained soluble on neutralisation, showing that it was not water
      insolubility that prevented their extraction with CDTA. Covalent bonding was
      thought more likely. 

PMID- 24276163
TI  - Lipid synthesis in the laticifers of Euphorbia lathyris L. seedlings.
AB  - Various solutions of labeled precursors were absorbed by the cotyledons of
      etiolated Euphorbia lathyris L. seedlings. Incorporation of (14)C into
      triterpenes from [2-(14)C]mevalonic acid, [1-(14)C]acetate, [3-(14)C]pyruvate, [U
      (14)C]glyoxylate, [U-(14)C]glycerol, [U-(14)C]serine, [U-(14)C]xylose, [U
      (14)C]glucose, and [U-(14)C]sucrose was obtained. The [(14)] triterpenes
      synthesized from [(14)C] sugars were mainly of latex origin. [(14)C]mevalonic
      acid was only involved in terpenoid synthesis outside the laticifers. Exogenously
      supplied glyoxylate, serine, and glycerol were hardly involved in lipid synthesis
      at all. The (14)C-distribution over the various triterpenols was consistent with
      the mass distribution of these constituents in gas liquid chromatography when
      [(14)C]sugars, [(14)C]acetate, and [(14)C]pyruvate were used. These precursors
      were supplied to the seedlings in the presence of increasing amounts of unlabeled
      substrates. The amount of substrate directly involved in lipid synthesis as well
      as the absolute triterpenol yield was calculated from the obtained
      [(14)C]triterpenols. The highest yield was obtained in the sucrose incorporated
      seedlings, being 25% of the daily increase of latex triterpenes in growing
      seedlings. 

PMID- 24276164
TI  - Morphogenesis of lucerne root nodules incited by Rhizobium meliloti in the
      presence of combined nitrogen.
AB  - Combined light and transmission electron microscopy were used to examine the
      effect of nitrate on the development of root nodules in lucerne (alfalfa,
      Medicago sativa L.) following induction by the nitrogen-fixing symbiont,
      Rhizobium meliloti. The timing of NO 3 (-) addition was varied in order to study
      its effect on all of the recognized morphogenetic steps of nodule formation.
      Roots of plants inoculated in the presence of 18 mM NO 3 (-) had straight root
      hairs which were devoid of adherent rhizobia and infection threads, and developed
      no nodules. However, nodules were formed on roots if 18 mM NO 3 (-) was added 5 d
      after inoculation. At this time, the initiation of nodule primordia had already
      commenced in the root cortex. The histology and ultrastructure of young nodules
      which had developed for 5 d in the absence of NO 3 (-) and another 5 d in the
      presence of 18 mM NO 3 (-) resembled nodules developing under N-free conditions,
      except that in the infection threads within the infection zone of the nodule 1)
      some bacteria tended to loose their normal shape and gain more electron density,
      indicating premature degradation, and 2) the matrix of the infection threads was
      abnormally enlarged. In the presence of high NO 3 (-) levels in the medium, lysis
      and degeneration of the bacteria released from the infection threads were
      observed in the infection and bacteroid zones of developing nodules, indicative
      of premature senescence. On the other hand, the nodule meristems continued to
      proliferate even after 12 d of exposure of 18 mM NO 3 (-) . This was the only
      morphogenetic step of root nodulation which was insensitive to levels of combined
      nitrogen that completely prevented infection if present at the time of
      inoculation. These data indicate that all of the recognized steps of root nodule
      morphogenesis in which the bacteria play a key role are sensitive to the
      inhibitory effect of combined nitrogen. 

PMID- 24276165
TI  - Action of light on accumulation of carotenoids and chlorophylls in the milo shoot
      (Sorghum vulgare Pers.).
AB  - We have performed a comprehensive study on the mechanism of regulation of
      carotenogenesis by light in the shoot of Sorghum vulgare. Our work shows that
      carotenoid accumulation is simultaneously controlled by phytochrome (Pfr) and by
      the availability of chlorophyll. Throughout plastidogenesis light dependent
      chlorophyll and carotenoid accumulation are interdependent processes:
      Accumulation of chlorophyll in natural light requires the presence of
      carotenoids; likewise, accumulation of considerable amount of carotenoids depends
      on the availability of chlorophyll. However, in both cases the efficiency of the
      biosynthetic pathway, the potential biosynthetic rates ("capacities") are
      determined by phytochrome. A "push and pull" model of carotenogenesis advanced
      previously (Frosch and Mohr 1980, Planta 148, 279) to explain carotenogenesis in
      the mustard (Sinapis alba) seedling also applies to the monocotyledonous milo
      (Sorghum vulgare) seedling. Therefore, we suggest that the model applies to
      carotenogenesis in higher plants in general. 

PMID- 24276166
TI  - Effect of cell turgor on hydraulic conductivity and elastic modulus of Elodea
      leaf cells.
AB  - Water relation parameters of leaf cells of the aquatic plant Elodea densa have
      been measured using the pressure probe. For cells in both the upper and lower
      epidermis it was found that the elastic modulus (epsilon) and the hydraulic
      conductivity (Lp) were dependent on cell turgor (P). Lp was (7.8+/-5.5).10(-7) cm
      s(-1) bar(-1) (mean+/-SD; n=22 cells) for P>4 bar in cells of the upper epidermis
      and was increasing by a factor of up to three for P->0 bar. No polarity of water
      movement or concentration dependence of Lp was observed. For cells of the lower
      epidermis the Lp-values were similar and the hydraulic conductivity also showed a
      similar dependence on turgor. No wall ingrowth or wall labyrinths (as in transfer
      cells) could be found in the cells of the lower epidermis. The elastic modulus
      (epsilon) of cells of the upper epidermis could be measured over the whole
      pressure range (P=0-7 bar) by changing the osmotic pressure of the medium.
      epsilon increased linearly with increasing turgor and ranged between 10 and 150
      bar. For cells of the lower epidermis the dependence of epsilon on P was similar,
      although the pressure dependence could not be measured on single cells. The Lp
      values are compared with literature data obtained for Elodea by a nuclear
      magnetic resonance (NMR)-technique. The dependence of Lp on P is discussed in
      terms of pressure dependent structural changes of the cell membranes and
      interactions between solute and water transport. 

PMID- 24276167
TI  - Seasonal changes in light transmission by bud scales of spruce and pine.
AB  - A bundle of optical fibres and a photometer were used to measure light
      transmission through bud scales of Norway spruce [Picea abies (L.) Karst.] and
      Scots pine (Pinus silvestris L.). Percentage transmission increases with
      wavelength from none below 480 nm to 3% the far-red. Transmission of all
      wavebands measured was lowest in late summer and winter and highest in the autumn
      and spring. For most of the year in pine, and only from July to September in
      spruce, there is a depression of red light (660-670 nm) transmission. This
      affects the ratio of 660/730 nm light penetrating the apical domes. This ratio is
      lowest in July and August, at the time of initiation of female strobili. The
      seasonal variation in transmission of light by bud scales is discussed in
      relation to the possible consequences for the control of flowering. 

PMID- 24276169
TI  - Improved estimation of protein-ligand binding free energy by using the ligand
      entropy and mobility of water molecules.
AB  - We previously developed the direct interaction approximation (DIA) method to
      estimate the protein-ligand binding free energy (DG). The DIA method estimates
      the DG value based on the direct van der Waals and electrostatic interaction
      energies between the protein and the ligand. In the current study, the effect of
      the entropy of the ligand was introduced with protein dynamic properties by
      molecular dynamics simulations, and the interaction between each residue of the
      protein and the ligand was also weighted considering the hydration of each
      residue. The molecular dynamics simulation of the apo target protein gave the
      hydration effect of each residue, under the assumption that the residues, which
      strongly bind the water molecules, are important in the protein-ligand binding.
      These two effects improved the reliability of the DIA method. In fact, the
      parameters used in the DIA became independent of the target protein. The averaged
      error of DG estimation was 1.3 kcal/mol and the correlation coefficient between
      the experimental DG value and the calculated DG value was 0.75. 

PMID- 24276168
TI  - Advances in Mammalian cell line development technologies for recombinant protein
      production.
AB  - From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have
      been approved by US Food and Drug Administration (FDA) annually. In addition, the
      expiration of blockbuster biologics has also spurred the emergence of
      biosimilars. The increasing numbers of innovator biologic products and
      biosimilars have thus fuelled the demand of production cell lines with high
      productivity. Currently, mammalian cell line development technologies used by
      most biopharmaceutical companies are based on either the methotrexate (MTX)
      amplification technology or the glutamine synthetase (GS) system. With both
      systems, the cell clones obtained are highly heterogeneous, as a result of random
      genome integration by the gene of interest and the gene amplification process.
      Consequently, large numbers of cell clones have to be screened to identify rare
      stable high producer cell clones. As such, the cell line development process
      typically requires 6 to 12 months and is a time, capital and labour intensive
      process. This article reviews established advances in protein expression and
      clone screening which are the core technologies in mammalian cell line
      development. Advancements in these component technologies are vital to improve
      the speed and efficiency of generating robust and highly productive cell line for
      large scale production of protein therapeutics. 

PMID- 24276170
TI  - In vitro assessment of clevidipine using the profilin1 hypertensive mouse model.
AB  - Hypertension represents a major risk factor for cardiovascular events,
      associating with vascular hypertrophy and dysfunction in resistance vessels.
      Clevidipine is a novel antihypertensive drug working as a selective calcium
      channel antagonist with an ultra-short half-life that lowers arterial blood
      pressure by reducing systemic arterial resistance. The aim was to assess the
      effect of clevidipine on the hypertrophic vessels of profilin1 hypertensive
      transgenic mice compared to sodium nitroprusside (SNP) and labetalol using wire
      myograph techniques. The effects of clevidipine, SNP and labetalol on the
      hypertrophic vessels were studied on mesenteric arterial function from 8
      profilin1 hypertrophic mice and eight non-transgenic controls. Our results showed
      a significant difference between the effects of the three drugs on the
      hypertrophic mesenteric arteries of transgenic profilin1 mice compared to the non
      transgenic controls. The half maximal effective concentration (EC50) of
      clevidipine, SNP and labetalol in profilin1 mice (1.90 +/- 0.05, 0.97 +/- 0.07,
      2.80 +/- 0.05 nM, respectively) were significantly higher than the EC50 in non
      transgenic controls (0.91 +/- 0.06, 0.32 +/- 0.06, 0.80 +/- 0.09 nM,
      respectively). Moreover, the increase in the EC50 for clevidipine (2-fold) to
      produce the same effect on both normal and hypertrophic arteries was less than
      that of SNP (3-fold) and labetalol (3.5-fold). Therefore, we concluded
      clevidipine exhibited the lowest dose shift to relax the hypertrophic vessels
      compared to SNP and labetalol in the profilin1 hypertrophic animal mouse model. 

PMID- 24276171
TI  - In Vivo Anti-Leukemia, Quantum Chemical Calculations and ADMET Investigations of
      Some Quaternary and Isothiouronium Surfactants.
AB  - Anti-leukemia screening of previously prepared isothiouronium and quaternary
      salts was performed, and some salts exhibited promising activity as anticancer
      agents. Quantum chemical calculations were utilized to explore the electronic
      structure and stability of these compounds. Computational studies have been
      carried out at the PM3 semiempirical molecular orbitals level, to establish the
      HOMO-LUMO, IP and ESP mapping of these compounds. The ADMET properties were also
      studied to gain a clear view of the potential oral bioavailability of these
      compounds. The surface properties calculated included critical micelle
      concentration (CMC), maximum surface excess (Gammamax), minimum surface area
      (Amin), free energy of micellization (DeltaGomic) and adsorption (DeltaGoads). 

PMID- 24276172
TI  - Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds
      through the Inhibition of Purinergic P2X Receptors.
AB  - Natural products have reemerged in traditional medicine as a potential source of
      new molecules or phytomedicines to help with health disorders. It has been
      established that members of the P2X subfamily, ATP-gated ion channels, are
      crucial to the inflammatory process and pain signalization. As such, several
      preclinical studies have demonstrated that P2X2R, P2X3R, P2X4R and P2X7R are
      promising pharmacological targets to control inflammatory and pain disorders.
      Several studies have indicated that natural products could be a good source of
      the new specific molecules needed for the treatment of diseases linked to
      inflammation and pain disorders through the regulation of these receptors.
      Herein, we discuss and give an overview of the applicability of natural products
      as a source to obtain P2X receptors (P2XR) selective antagonists for use in
      clinical treatment, which require further investigation. 

PMID- 24276173
TI  - Evolution of biologics screening technologies.
AB  - Screening for biologics, in particular antibody drugs, has evolved significantly
      over the last 20 years. Initially, the screening processes and technologies from
      many years experience with small molecules were adopted and modified to suit the
      needs of biologics discovery. Since then, antibody drug discovery has matured
      significantly and is today investing earlier in new technologies that commercial
      suppliers are now developing specifically to meet the growing needs of large
      molecule screening. Here, we review the evolution of screening and automation
      technologies employed in antibody discovery and highlight the benefits that these
      changes have brought. 

PMID- 24276174
TI  - Early use of surfactant and nitric oxide.

PMID- 24276175
TI  - Pleural effusion as a complication of a remotely placed catheter in a preterm
      infant.

PMID- 24276176
TI  - Local facial cutaneous vasoconstriction: an unusual complication of inhaled
      racemic epinephrine in a neonate.
AB  - A term infant treated for post-extubation stridor with nebulized racemic
      epinephrine developed localized facial blanching due to cutaneous absorption of
      the aerosolized vasoconstrictor. Local application of heat restored circulation
      to the afflicted area. This complication of a commonly used medication is not
      previously reported in the medical literature and has the potential for severe
      sequelae. 

PMID- 24276177
TI  - Encephalocele following a periconceptional exposure to efavirenz: a case report.
AB  - The use of Efaverinz in reproductive age women needs caution as its use in the
      first trimster of pregnancy is reportedly associated with an increased risk of
      neural tube defect (NTD) in the newborn. This concern is based on evidence from
      animal studies and two human case reports. We report here yet another case of
      encephalocele born from a mother who was taking efaverenze during conception and
      the first 8 weeks of gestation, the critical time in the pathogenesis of NTDs. 

PMID- 24276178
TI  - Human-centered incubator: beyond a design concept.

PMID- 24276179
TI  - Encouraging developments in incubator design.

PMID- 24276180
TI  - [Medical teaching. The challenge of digital natives in education].

PMID- 24276181
TI  - [Factors that predict depression in medical students].
AB  - INTRODUCTION: High prevalence of depression and anxiety symptoms has been
      observed in medical students. OBJECTIVE: To identify predictors of depressive
      symptoms according to CES-D in students during their first year of medical
      education. METHODS: We evaluated 517 students in their first year of medical
      education with the following instruments: Centers for Epidemiology Studies for
      Depression Scale, State-Trait anxiety inventory, and stressors list. A linear
      regression analysis was carried out to evaluate variables predicting high CES-D
      scores. RESULTS: We observed that anxiety and depressive symptoms were more
      frequent in women, as well as stressors. Predictors of depression were state of
      anxiety, stressors, and low socioeconomic level. CONCLUSIONS: It is important to
      implement support measures for students who live with stress factors, suffering
      anxiety, or with a low socioeconomic level.

PMID- 24276182
TI  - [Electroencephalographic and neurodevelopmental disorders in toddlers with severe
      congenital heart diseases. Preliminary study].
AB  - Within the field of pediatric heart disease, congenital cardiopathology is the
      most important issue due to the fact that in these patients a delay of
      neurodevelopment is the most frequent morbidity. The major aim of this work was
      to determine the impact of severe congenital cardiopathology (SCC) on the central
      nervous system (CNS) through the study of the electroencephalogram (EEG) and the
      assessment of neurodevelopment. POPULATION AND METHODS: Children under 3 years
      old, 41 of them presenting SCC and 15 healthy controls (C) were studied.
      Conventional EEG recording and assessment of neurodevelopment were performed.
      RESULTS: In twenty children presenting SCC (48.8%) the EEG was found abnormal
      (paroxysmal of spikes and sharp waves). Forty of them (97.6%) presented
      neurodevelopmental alterations, including hypotonia and a delay in gross motor
      skills. When comparing EEG between SCC and C children, odds ratio was 13.33
      (1.602-111) and comparing neurodevelopment delay, it was 35 (3.769-235). Both
      were statistically significant (p <= 0.00039 and p <= 0.00038, respectively).
      CONCLUSIONS: A high percentage of children suffering from SCC exhibited EEG
      patterns with abnormal epileptic-like activity although without clinical
      manifestation of seizures. These children also showed delay features in different
      areas of neurodevelopmental. The assessment of new born carrying some type of
      severe cardiopathology indicated that they were under high risk of suffering from
      CNS altered development.

PMID- 24276183
TI  - [Early analgesia does not block labor in first pregnancies].
AB  - Pain during labor alters the well-being of the mother and fetus. Peridural
      analgesia may prevent pain, but some physicians prefer to administrate this until
      labor has progressed in order to avoid blocking labor so a cesarean surgery would
      be required. In this case, the mother suffers pain until labor has progressed
      enough to apply analgesia. Thus, the mother suffers pain while labor has
      progressed enough. Cesarean surgery increases maternal morbidity, thus it is
      important to evaluate labor progression when analgesia is applied at an early or
      advanced stage of labor. This study evaluated the effect of early analgesia on
      labor progression. First pregnancies at a latent or active stage of labor were
      included. Ropivacaine peridural analgesia was applied. All the patients completed
      labor (latent labor: final dilation 10 cm (10-10 cm); active labor: final
      dilation 10 cm (10-10 cm); p = 0.812). The proportion of patients undergoing
      cesarean surgery was not different between the groups (four in latent labor (7%),
      eight in active labor (12%); p = 0.545). Our results suggest that early analgesia
      may be applied without compromising labor progression. 

PMID- 24276184
TI  - [Incidence of congenital heart disease and factors associated with mortality in
      children born in two Hospitals in the State of Mexico].
AB  - We studied the incidence, survival, and risk factors for mortality in a cohort of
      infants for a period of five years, born in two hospitals, one a second-level
      General Hospital, the second a tertiary perinatal hospital, both in the City of
      Toluca. The analysis of survival was performed with the Kaplan-Meier method, and
      Cox regression was used to estimate the risk of death according to different
      factors. We found an overall incidence of 7.4 per 1,000 live births; in preterm
      infants, the rate was 35.6 per 1,000, and in term newborns it was 3.68 per 1,000.
      The most common heart disease was the ductus arteriosus in the overall group and
      in preterm infants; in term newborns the most common was the atrial septal
      defect. The specific mortality was 18.64%, follow-up was 579 days, where we
      found, according to Kaplan-Meier, survival of an average of 437.92 days, with 95%
      confidence intervals of 393.25 to 482.6 days, with a standard error of 22.79
      days; the cumulative probability of survival was 0.741, with a standard error of
      0.44. In Cox regression, two variables had a high hazard ratio (HR): these were
      the presence or absence of cyanosis and the hospital where they were treated as
      newborns. 

PMID- 24276185
TI  - [Vision-threatening retinopathy in diabetics not referred to an ophthalmologist].
AB  - BACKGROUND: Vision-threatening forms of diabetic retinopathy (macular edema and
      proliferative retinopathy) can be efficiently treated with laser. Any delay in
      access to ophthalmic care may limit the opportunity of treatment. Diabetics that
      are not referred to an ophthalmologist are a vulnerable population, which could
      lose vision as a result of delayed attention. MATERIAL AND METHODS:
      Observational, descriptive, prospective, cross-sectional study in diabetics
      attending a hospital for non-ophthalmological causes, without prior evaluation of
      the ocular fundus. The proportion of eyes with vision-threatening diabetic
      retinopathy, and that of eyes in which visual loss could be prevented were
      identified. RESULTS: 100 patients, mean age 55.5 years, 53 females; 48 had
      diabetic retinopathy, six had proliferative retinopathy (6%; 95% CI: 1.3-10.7),
      and 23 had macular edema (23%; 95% CI: 14.8-31.2); the proportion of diabetic
      macular edema was higher than the one reported in the same population 15 years
      before (odds ratio 4.01; 95% CI: 1.98-8.15). Fifty-six percent of the patients
      with vision-threatening retinopathy did not have visual deficiency. CONCLUSION:
      Detection and referral of diabetic patients with risk of visual loss must be made
      easier, regardless of their visual symptoms, in order to achieve treatment
      efficacy by timely care.

PMID- 24276186
TI  - [Mechanisms of suppression of regulatory T-cells (Treg)].
AB  - An important feature of immunology is understanding how the immune system is able
      to discriminate between self and non-self. Regulatory T-cells (Treg) actively
      inhibit immune responses involved in the pathological and physiological
      responses, and, in consequence, contribute to the maintenance of homeostasis. The
      characterization of these regulatory T-cells has been controversial due to the
      lack of exclusive markers for their identification and isolation. The mechanisms
      that regulatory T-cells use to function are: cytokines, death cells, modullation
      of the microenvironment, and surface receptors. The immune system and Treg cells
      have been related to obesity and type 2 diabetes mellitus through the
      inflammatory process. In this work, we review the proposed markers for Treg
      cells, recent data on the mechanism used for the main function of Treg cells,
      immune regulation, and we conclude with the impact of these cells on obesity and
      type 2 diabetes mellitus. 

PMID- 24276187
TI  - [Neuroendocrine differentiation in prostate adenocarcinoma].
AB  - The human prostate is a gland composed of many types of cells and extracellular
      components with specific functions. The stromal compartment includes nerve
      tissue, fibroblasts, lymphocytes, macrophages, endothelial cells, and smooth
      muscular cells. The epithelial compartment is composed of luminal epithelial
      cells, basal cells, and a lesser number of neuroendocrine cells, which are
      transcendental in growth regulation, differentiation, and secretory function. In
      prostate cancer, neuroendocrine cells replicate especially in high grade and
      advanced stage, and hormonally treated tumoral cells adopt characteristics that
      make them resistant to hormonal deprivation. Androgen receptors have a crucial
      role in tumorigenesis of prostate adenocarcinoma. Deprivation hormone therapy
      blocks the expression of androgen receptors in the prostatic epithelial cells.
      Neuroendocrine cells lack androgen receptors; their growth is hormonally
      independent and that is why deprivation hormonal therapy does not eliminate the
      neoplasic neuroendocrine cells. In contrast, these types of cells proliferate
      after therapy and make a paracrine network, stimulating the proliferation of
      androgen-independent neoplastic cells, which finally lead to tumoral recurrence.
      In this work we describe the neuroendocrine function in normal tissue and in
      prostatic adenocarcinoma, including neoplasic proliferation stimulation,
      invasion, apoptosis resistance, and angiogenesis, and describe some molecular
      pathways involved in this neuroendocrine differentiation. 

PMID- 24276188
TI  - [Tyrosine kinase inhibitors (TKI): a new revolution in the treatment of chronic
      myeloid leukemia (CML)].
AB  - Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia
      associated with the t(9,22)(q34:q11) reciprocal translocation, also known as
      Philadelphia chromosome (Ph). As a result of such abnormality, a chimeric gene
      (bcr-abl) is produced that is translated into a chimeric protein (BCR-ABL), a
      constitutively activated tyrosine kinase. Major cell dysfunctions result from
      this abnormal kinase activity, including increased proliferation and reduced
      apoptosis. Based on the structure of BCR-ABL, several molecules have been
      designed that inhibit its kinase activity. Five such molecules have already been
      brought into the clinic for the treatment of Ph+ CML patients. Good results have
      been obtained in terms of patients' remission rates and quality of life. Some
      major problems, however, have been observed. Firstly, a significant proportion of
      patients develop resistance to the drugs; secondly, it is clear that such drugs
      affect most of the leukemic cells, but do not eliminate leukemia stem cells.
      Thus, important CML-related challenges remain to be solved in the near future. 

PMID- 24276189
TI  - [Involvement of matrix metalloproteinases in acute coronary syndrome (ACS)].
AB  - Matrix metalloproteinases (MMP) are enzymes that degrade extracellular matrix
      (ECM) proteins and regulate both their accumulation and composition. The MMP are
      involved in the atherosclerotic process since they contribute to the formation of
      the plaque and its subsequent rupture. This last step triggers the myocardial
      ischemia that will be clinically reflected as an acute coronary syndrome (ACS).
      Thus, MMP activity is a key to whether ACS develops or not. With an elevated
      transcription rate of the genes that codify these proteinases comes a higher
      enzymatic activity. This explains that if a polymorphism in the mentioned genes
      modifies transcription, there could be a predisposition to developing ACS.
      Several studies reveal that certain genetic variations in MMP-1, -2, -3, -7, -8, 
      9, -12, and -14 have an important role either as risk factors or as protective
      factors for the expression of ACS. 

PMID- 24276190
TI  - [Primary hyperaldosteronism by unilateral adrenal hyperplasia: a report of two
      cases].
AB  - Primary aldosteronism (PA) is actually the main cause of adrenal-endocrine
      hypertension. This syndrome is characterized by hypertension, hypokalemia,
      suppressed plasma renin activity, and increased aldosterone excretion. The most
      common causes of this syndrome are bilateral idiopathic hyperaldosteronism and
      aldosterone producing adenoma (Conn's syndrome) and less frequently unilateral
      adrenal hyperplasia, adrenal carcinoma, or familial hyperaldosteronism.
      Unilateral adrenal hyperplasia (UAP) constitutes 2% of the causes of PA. We
      present the case of two patients with UAP. 

PMID- 24276191
TI  - [Metastatic oropharyngeal squamous cell carcinoma in cervical lymph nodes
      associated to HPV infection type 16 and 45; clinical, morphological and molecular
      study of two cases].
AB  - Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has
      been identified as a distinct entity within squamous cell carcinoma of the head
      and neck. In contrast to carcinomas associated with alcohol and/or tobacco, this
      subtype occurs at younger age, with frequent absence of classic risk factors,
      correlation with oral sexual habits, strong predilection for the palatial tonsils
      and the base of the tongue (lingual tonsils), basaloid or lymphoepithelial
      differentiation, higher degree of radiosensitivity, and overall better survival.
      We report two cases of lymph node, metastatic, poorly differentiated squamous
      cell carcinoma that were positive by immunohistochemistry for p16 with detection
      of HPV-16 and HPV-45 by PCR. 

PMID- 24276192
TI  - [Molecular gerontology: towards healthy aging].
AB  - For many years aging research was confined to statistics, psychology, and
      socioeconomic aspects of old age. However, today the study of aging is one of the
      most attractive and prosperous fields in biology. This change followed on from
      observations that single gene mutations can modulate the aging process,
      demonstrating the dynamic and plastic nature of the pathways involved. The field
      of aging is continually being fuelled by the discovery of new genes and pathways
      that extend lifespan when manipulated in organisms ranging from unicellular yeast
      to the more complex round worm C. elegans and the fruit fly Drosophila
      melanogaster. Such interventions have also been successful in mammals, proving
      the principle that discoveries in invertebrates can be evolutionarily relevant to
      humans. The most successful and evolutionary conserved interventions are those
      related to nutrient sensing pathways, the effector pathways upon which dietary
      restriction operates to promote health and longevity. To validate the existence
      of genes that modify the aging process in humans, biogerontologists have opted
      for a genome-wide approach to studying centenarians, those fortunate to live
      beyond 100 years of age. By studying these individuals, they hope to unravel the
      genetic signatures that promote healthy ageing and long life. 

PMID- 24276193
TI  - [Constitutional analysis of Mexican Official Norm NOM-174-SSA1-1998 for the
      handling of obesity].
AB  - The First Chamber of the Mexican Supreme Court of Justice decided, by a majority
      of four votes, on a case where it had to be evaluated if some articles of a
      Mexican Official Norm (NOM) on obesity violated human rights. The majority in the
      chamber concluded that the restrictions went against Medics' prescribing or
      therapeutic rights, and therefore their freedom to work. Justice Cossio Diaz
      voted against the judgment and wrote a separate opinion where he holds, first of
      all, that the prescribing right works as a guideline for the medical profession
      and is not an essential element of the freedom to work. Secondly, he points out
      that the freedom to work is not an absolute right, for it has certain limits
      permitted by the Constitution. Consequently, experts' opinions should have been
      consulted for them to be able to determine if the NOM's requirements were in
      accordance with the Constitution. Finally, he considers that the judgment should
      have introduced a balancing test between freedom to work and the patient's health
      rights, since this last-mentioned right was what the NOM intended to protect. 

PMID- 24276194
TI  - Precise characterization of cuticular compounds in youngDrosophila by mass
      spectrometry.
AB  - Cuticular hydrocarbons of youngDrosophila flies are singular with very long
      chains and complex diene mixtures. A precise characterization of these substances
      was carried out by epoxidation and analysis of the products by GC-MS with
      negative chemical ionization. InD. melanogaster, double bonds of dienes are more
      probable at carbon positions 11 or 13 and 21 or 23. InD. simulans, double bonds
      are shifted more towards the interior of the chain. Such a difference is also
      found among monoenes of both species. The analyses of monoenes and dienes confirm
      the similarity of cuticular compounds of young flies of both sexes in both
      species. A main cuticular compound ofD. erecta females, 9, 23-tritriacontadiene,
      is also presented. 

PMID- 24276195
TI  - Effect of juvenile hormone analog, fenoxycarb, on pheromone production byIps
      paraconfusus (Coleoptera: Scolytidae).
AB  - Topical application of the juvenile hormone analog, fenoxycarb, in acetone
      induced newly emerged male California five-spined ips,Ips paraconfusus Lanier, to
      become attractive to females, as measured by positive responses to male abdominal
      extracts in a laboratory bioassay. Two pheromones, ipsdienol and ipsenol, were
      detected by gas chromatography in the abdominal extracts of fenoxycarb-treated
      males. Pheromone production was minimal at a dose of 0.1 MUg/insect of
      fenoxycarb, maximal at 10 MUg, and was reduced to unmeasurable amounts at a dose
      of 100 MUg. In comparison, peak production of pheromones was induced at a dose of
      0.1 MUg/insect of natural juvenile hormone (JH III). Treatment with 10 MUg of
      fenoxycarb resulted in the occurrence of pheromones 12 hr after exposure, maximal
      pheromone content between 16 and 20 hr, and undetectable amounts after 36 hr. The
      demonstration that fenoxycarb is an active juvenile hormone analog for a bark
      beetle suggests that it may have practical utility in managing these insects. 

PMID- 24276196
TI  - Butenolides in small ermine moths,Yponomeuta spp. (Lepidoptera: Yponomeutidae),
      and spindle-tree,Euonymus europaeus (Celastraceae).
AB  - A new butenolide, isosiphonodin [3-hydroxymethyl-2(5H)-furanone], along with a
      trace of siphonodin [4-hydroxymethyl-2(5H)-furanone], was isolated from fifth
      instar larvae of the small ermine mothYponomeuta cagnagellus. Leaves of its host
      plant spindle-tree,Euonymus europaeus, were found to contain the same two
      butenolides with siphonodin being present as the major compound. TLC showed that
      isosiphonodin was also present in larvae or pupae of six other small ermine moths
      which did not feed on spindle-tree. InY. cagnagellus butenolides might be plant
      derived, while isosiphonodin in the other investigated small ermine moths is
      probably synthesized by the insect. The possible role of butenolides in the
      chemical defense of small ermine moths is discussed. 

PMID- 24276197
TI  - Damage-induced alkaloids in tobacco: Pot-bound plants are not inducible.
AB  - Field-grown wild tobacco plants (Nicotiana sylvestris) were subjected to a
      defoliation regime designed to mimic the rate and amount of leaf mass removed by
      one tobacco hornworm per plant. Undamaged leaves on these plants undergo a
      dramatic (457% for leaf position 5, 410% for leaf position 8) increase in total
      leaf alkaloids compared to same-age and positioned control leaves on undamaged
      control plants. However, potted greenhouse-grown plants fail to exhibit the same
      damage-induced increase in alkaloid content. The greenhouse environment differs
      from the field environment in factors known to influence leaf alkaloid content,
      particularly soil N, P, K, near-UV radiation, and relative humidity. However,
      altering these environmental factors does not make potted plants able to increase
      their leaf alkaloid levels in response to defoliation. Transplanting plants into
      larger pots with more soil does allow the plants to respond to defoliation.
      Thirty days after transplanting, the plants are again unresponsive to damage,
      probably as a result of becoming "pot-bound." This result suggests a mechanism
      for the induction response, specifically that leaf damage triggers synthesis of
      these alkaloids in the roots, and offers a potentially valuable experimental tool
      for the study of induced-plant defenses in tobacco and other plants that
      synthesize alkaloids in their root tissues. 

PMID- 24276198
TI  - Identification of a male-produced pheromone ofAnticarsia gemmatalis (Hubner)
      (Lepidoptera; Noctuidae) attractive to conspecific males.
AB  - Observations in the laboratory and in the field indicated that maleAnticarsia
      gemmatalis (Hubner), the velvetbean caterpillar (VBC), are attracted to
      conspecific courting males. Male VBC subsequently were found to be attracted to
      extracts of male abdominal tips including the extrudable hairpencils. The active
      chemical in these extracts was identified as (Z,Z,Z)-3,6,9-heneicosatriene, which
      is also one of the major components of the female VBC sex pheromone. Male VBC in
      a wind tunnel and in the field exhibited a bimodal response distribution to a
      range of ratios of the (Z,Z,Z)-3,6,9-heneicosatriene and (Z,Z,Z)-3,6,9
      eicosatriene, with one maximum at the pure heneicosatriene alone and the other at
      the 60?40 female blend. This demonstrates that the male response to the male
      hairpencil component is distinct from that to the female sex pheromone. 

PMID- 24276199
TI  - Pheromone-dependent species recognition mechanisms betweenNeodiprion pinetum
      andDiprion similis on white pine.
AB  - The sex pheromones ofNeodiprion pinetum (Norton) andDiprion similis (Hartig)
      consist of two isomers, 2S,3S,7S and 2S,3R,7R, in either the acetate orpropionate
      forms of 3,7-dimethylpentadecan-2-ol, respectively. The 2S,3S,7S acetate isomer
      is utilized byN. pinetum as the major pheromone component and the 2S,3R,7R
      acetate as a Synergist. ConverselyD. similis utilizes 2S,3R,7R as propionate the
      major pheromone component and 2S,3S,7S propionate as a Synergist. This was
      confirmed in the field in both Michigan and Wisconsin. Capillary gas-liquid
      chromatographie analyses revealed that these two isomers are present in the
      natural pheromones of both species at the ratios close to those predicted by
      artificial blending of the two optical isomers. 

PMID- 24276200
TI  - Himachalol andbeta-himachalene: Insecticidal principles of himalayan cedarwood
      oil.
AB  - Chromatographic fractions of Himalayan cedarwood oil (Cedrus deodara) were
      bioassayed against the pulse beetle (Callosobruchus analis F.) and the housefly
      (Musca domestica L.). Almost all fractions showed insecticidal activity against
      both test species. Fractions I and V led to the highest mortality and also
      produced a quick knockdown effect. Fractions I and V, after rechromatography and
      purification, yielded himachalol (3%) and beta-himachalene (31%), based on
      essential oil weight, respectively. Further evaluation of these two naturally
      occurring sesquiterpenes indicated 97.5% mortality at 0.56 MUmol/insect against
      the pulse beetle. These biologically active natural products of plant origin may
      serve as a suitable prototypes for development of commercial insecticides. 

PMID- 24276201
TI  - Identification of thoracic gland constituents from maleXylocopa spp. latreille
      (Hymenoptera: Anthophoridae) from arizona.
AB  - Some male carpenter bees (Xylocopa spp.) possess massive propodeal exocrine
      glands that produce copious quantities of multicomponent blends of lipoidal
      material. Some of these compounds are volatile, producing a "flowery" aroma that
      can be easily detected several meters downwind from a territorial male. Chemical
      characterization of these secretions showed them to be blends of terpenoid
      compounds or fatty acid derivatives. InX. varipuncta, the mixture is composed of
      alltrans-geranylgeraniol, alltrans-farnesal, and an isomer of 3,7, 11-trimethyl
      2,7,10-dodecatrienal in an approximate 9?6?1 ratio. The secretion ofX. micheneri
      contains isopropyl oleate, (Z)-11-eicosen-1-ol, oleyl alcohol, and methyl
      palmitate at approximately 63?24?11?1. We hypothesize that these compounds act as
      pheromones that aid in attracting and holding conspecific females to symbolic
      nonresource encounter sites where mating occurs. They also appear to have utility
      as chemotaxonomic markers at the subgeneric level. 

PMID- 24276202
TI  - Pheromone gland components of some australian tortricids in relation to their
      taxonomy.
AB  - A survey has been carried out to identify the major sex pheromone gland
      components in 30 species of Australian tortricid moths. While more than half the
      species examined have (Z)-11-, (E)-11-, and/or (Z)-9-tetrade-cenyl acetates as
      the principal components, these compounds were not detected in some plesiomorphic
      taxa where combinations of (Z)-5 and (Z)-7 or (Z)-8 and (Z)-10 isomers are
      present. The results are discussed in relation to tortricid classification and
      current theories on pheromone evolution. 

PMID- 24276203
TI  - Responses of northern and western corn rootworms to semiochemical attractants in
      corn fields.
AB  - Small plots (18 * 18 m) were treated with grids of cotton wicks that contained
      semiochemicals for adultDiabrotica barberi Smith and Lawrence, the northern corn
      rootworm (NCR). In plots treated with eugenol (350 g/hectare), NCR were attracted
      to point sources of the compound, but there were no significant changes in
      numbers of either NCR orD. virgifera virgifera LeConte, the western corn rootworm
      (WCR), found on plants in the plots. In plots treated with 12.5 mg/hectare of 8R
      methyl-2R-decyl propanoate (2R,8R-MDP, the apparent female-produced sex pheromone
      of NCR and WCR), males of both species were attracted to point sources, but
      beetles did not congregate within treated plots. With racemic 2,8-MDP at 1.0
      g/hectare, male WCR were attracted into plots, but NCR of both sexes were
      strongly repelled. In a separate study, capture of beetles at pheromone-baited
      traps declined when the surrounding area contained wicks that emitted racemic 2,8
      MDP. In treated plots, male WCR were relatively inefficient at finding pheromone
      sources. With NCR, emigration from plots could account totally for the observed 3
      to 10-fold reduction in catch at 0.01-1.0 g/hectare. 

PMID- 24276204
TI  - Multivariate analysis of the correlation between noctuidae subfamilies and the
      chemical structure of their sex pheromones or male attractants.
AB  - Female-emitted pheromones and sex attractants of Noctuidae were investigated
      using a specific computer procedure to analyze data collected from the
      literature. Correspondence analysis was used to survey the structure-activity
      relationships of sex pheromones in seven subfamilies. Structural, stereochemical,
      and functional features of active molecules were related to taxonomy. This
      multidimensional analysis revealed that the prevalent chemical frame of noctuid
      moth pheromones was a monounsaturated acetate withZ stereochemistry and a double
      bond on the fifth carbon closest to the nonfunctional branch of the molecule.
      Possible phylogenetic relationships within Noctuidae and between Noctuidae and
      other families are discussed in light of the sex pheromone biochemistry. Female
      sex pheromones appeared to be an additional character to be considered in the
      classification of noctuid moths. 

PMID- 24276205
TI  - Antennnal olfactory and behavioral response of southern pine beetle,Dendroctonus
      frontalis, to analogs of its aggregation pheromone frontalin.
AB  - Antennal olfactory (electroantennogram) and laboratory and field behavioral tests
      were carried out on the response ofDendroctonus frontalis to its aggregation
      pheromone frontalin and analogs. The analogs were compounds modified by altering
      the position and methyl groups and/or by their deletion. Any modification to the
      frontalin structure significantly reduced both the antennal olfactory and
      behavioral response byD. frontalis. Beetle response, although significantly
      reduced, was elicited at the receptor level and in a laboratory bioassay by all
      analogs. However, only one analog (endo-5,7-dimethyl-Frontalin) elicited
      significant response from field populations of the beetle. 

PMID- 24276206
TI  - Astringency of douglas-fir foliage in relation to phenology and xylem pressure
      potential.
AB  - Astringency (tannin content) of Douglas-fir [Pseudotsuga menziesii (Mirb.)
      Franco] foliage was examined in relation to phenology and water status. Foliage
      was sampled from control trees, trees on south-facing slopes, and trenched trees
      prior to budbreak and at periods of two, six, and 12 weeks after budbreak.
      Astringency of prebudbreak foliage from untrenched trees was comparable to that
      of mature foliage. Foliage expansion was accompanied by dilution of the tannin
      content. Percent relative astringency of control trees was significantly and
      positively related to the absolute value of predawn xylem pressure potential,
      while this relationship was negative for trees in the south-facing group.
      Coefficients of determination for the relationship between astringency and
      predawn xylem pressure potential were high (0.67 and 0.79 for the control and
      south-facing groups, respectively). Astringency of foliage from trees in the
      south-facing group also was affected significantly by daytime xylem pressure
      potential. Astringency of foliage from trees in the control and south-facing
      groups was not significantly related to tissue age, while that from trenched
      trees was significantly related only to age. Results demonstrate that water
      status is a better predictor of foliage astringency than is tissue age in
      unperturbed trees of this species and that, depending on the magnitude and/or
      timing of water deficits, opposite relationships between astringency and xylem
      pressure potential can be observed. 

PMID- 24276207
TI  - Comparative effects of two plant secondary metabolites on host-parasitoid
      association.
AB  - Two plant-derived allelochemicals, berberine and alpha-terthienyl (alpha- T),
      were tested for their effects on the European corn borer,Ostrinia nubilalis, and
      its endoparasitoidDiadegma terebrans. The compounds were administered to the host
      insect in meridic diets, and the responses of the host larvae and parasitoids
      reared from treated hosts were measured in terms of growth parameters and
      survival. InO. nubilalis, survival to pupation and adult emergence were reduced
      significantly by the inclusion of berberine and alpha-T in larval diets at a
      concentration of 100 MUg/g. However, in the parasitoid, adverse effects were much
      more apparent with the alpha-T treatment than with the berberine treatment. alpha
      T and one of its metabolites were found in host larvae and in emerged adult
      parasitoids and their cocoons. Berberine residues were not detected. The
      implications of these responses to compounds of widely differing physiological
      properties are discussed with reference to host-plant resistance and biological
      control. 

PMID- 24276208
TI  - alpha-Tomatine and resistance of tomato cultivars toward the nematode,Meloidogyne
      incognita.
AB  - Susceptible and resistant tomato cultivars were assayed for root tomatine
      concentrations at different developmental times. No correlation between high
      tomatine levels and resistance towardMeloidogyne incognita was apparent. In
      plants infected with nematodes, tomatine in the roots was the same as in
      uninfected controls. Tomatine concentration, as measured by bulk analysis, does
      not appear to play an important role in resistance toward the nematode studied. 

PMID- 24276209
TI  - Influence of trichome exudates from species ofLycopersicon on oviposition
      behavior ofHeliothis zea (Boddie).
AB  - Cage experiments revealed that accessions of the wild tomato speciesLycopersicon
      hirsutum were preferred sites for oviposition byHeliothis zea. Hexane extracts
      from the leaves ofL. hirsutum were also preferred sites of oviposition in choice
      experiments among extracts from severalLycopersicon species. Extracts ofL.
      hirsutum were still biologically active several days after application,
      indicating that the phytochemical(s) involved are relatively stable and of low
      volatility. Gas Chromatographic analysis of leaf hexane extracts from 12
      different accessions of theL. hirsutum complex and three tomato cultivars
      revealed substantial qualitative and quantitative variation in the chemical
      composition of these extracts. Comparison of these results with extract
      oviposition studies implicate a group of structurally related compounds as the
      active agents. Mass spectroscopy has tentatively identified these compounds as
      sesquiterpenes with the chemical formula C15H22O2. These compounds are apparently
      synthesized and secreted from glandular trichomes on the leaf surface. These
      phytochemicals did not stimulate ovipositional behavior in females of the cabbage
      looper,Trichoplusia ni. The existence of genetic variation for the presence and
      amount of kairomones that serve as cues for insect orientation and oviposition
      could be utilized in a breeding program to develop tomato cultivars with
      genetically modified allelochemic profiles that would disrupt the sequential
      behavioral processes of insect host-plant selection. 

PMID- 24276210
TI  - Detoxification of isothiocyanate allelochemicals by glutathione transferase in
      three lepidopterous species.
AB  - Glutathione transferase activity towards various plant isothiocyanates was
      studied in larvae of the two generalists, fall armyworm [Spodoptera frugiperda
      (J.E. Smith)], and cabbage looper [Trichoplusia ni (Hubner)], and the specialist,
      velvetbean caterpillar (Anticarsia gemmatalis Hubner) using the midgut soluble
      fraction as enzyme source. The generalists, but not the specialist, are adapted
      to feeding on isothiocyanate-containing crucifers. Allyl and benzyl
      isothiocyanate were found to be metabolized by glutathione transferase from the
      two generalist species, but no activity was detected with the specialist. The
      transferase activity towards these allelochemicals in the cabbage looper was two-
      to sixfold higher than that in the fall armyworm. In all instances, activity was
      induced by various allelochemicals including indole 3-acetonitrile, indole 3
      carbinol, flavone, xanthotoxin, and its own substrates. The induction ranged from
      1.3- to 10.1-fold depending on the allelochemical, with the fall armyworm being
      more inducible. The transferase system of fall armyworm also metabolized another
      analog, 2-phenylethyl isothiocyanate, but activity can only be observed after
      induction. Bioassay results showed that these isothiocyanates were all toxic to
      the lepidopterans, causing acute toxicity in neonates and final-instar larvae.
      The results suggest that glutathione transferase plays an important role in the
      detoxification of isothiocyanates and hence food-plant adaptation in phytophagous
      insects. 

PMID- 24276211
TI  - Antennal olfactory responsiveness of three sympatricIps species [Ips avulsus
      (Eichhoff),Ips calligraphus (Germar),Ips grandicollis (Eichhoff)], to intra- and
      interspecific behavioral chemicals.
AB  - Electroantennograms (EAGs) from male and femaleIps avulsus, I. calligraphus,
      andI. grandicollis to their pheromones and selected host odorants or kairomones
      verified the presence of antennal olfactory receptors in both sexes of each
      species capable of detecting ipsdienol, ipsenol,cis- andtrans-verbenol,endo
      brevicomin alpha-pinene, frontalin, and verbenone. Each species possesses
      receptors with lower thresholds and in greater abundance for the compounds they
      produce and to which they are behaviorally most responsive. Detection of bothIps
      andDendroctonus pheromones by the three cohabiting species provides a sensory
      basis for olfactory interactions among the species. Differences in both threshold
      and saturation levels for EAGs for the various behavioral chemicals could denote
      differences in specific behavioral roles for each compound. 

PMID- 24276212
TI  - Sites of production and occurrence of volatiles in Douglas-fir
      beetle,Dendroctonus pseudotsugae hopkins.
AB  - Volatiles were found to be distributed throughout adult Douglasfir
      beetles,Dendroctonus pseudotsugae Hopkins, suggesting that the hindgut may not be
      the sole site of production. The volatile content of individual beetles increased
      dramatically with feeding; qualitative changes reflected the different bark
      habitats of newly emerged and established beetles. All detected volatiles were
      also found in beetle frass. Myrcene was the predominant monoterpene of emergent
      beetles and alpha-pinene of fed beetles. Linalool and bornyl acetate occurred in
      significant amounts after feeding, and diacetone alcohol and sulcatol were also
      detected for the first time. The presence of sulcatol explains the reported cross
      attraction withGnathotrichus spp.cis-Verbenol was also found to occur in addition
      totrans-verbenol. The volatile content of male beetles was similar to that of
      females but amounts of individual compounds were less. Acetic acid was found in
      both emerged and fed beetles and in lesser amounts in frass, suggesting that
      microbial metabolism could be a potential source of volatile production. 

PMID- 24276213
TI  - Aggregation pheromones inDrosophila borealis andDrosophila littoralis.
AB  - Mature males ofDrosophila borealis andD. littoralis (Diptera: Drosophilidae)
      produce pheromones that attract both males and females in a wind-tunnel bioassay.
      Ethyl tiglate is a major pheromone component in both species. Isopropyl tiglate
      is a minor component, as active as ethyl tiglate on an equal-weight basis, but
      less abundant in the flies. Both species respond to (Z)-9-heneicosene, a compound
      they do not possess, but which is a pheromone component in closely related
      species.D. borealis andD. littoralis are also able to discriminate among various
      heneicosene isomers. These responses to hydrocarbons may represent artifacts of
      evolution in this group. For both species, the pheromone was strongly synergized
      by an extract of fermenting aspen bark, a "host" material ofD. borealis. Benzyl
      alcohol was identified as one active component, although it did not account for
      all the activity of the extract. In nature, the flies probably respond to
      mixtures of fly-derived and host-derived volatiles. 

PMID- 24276214
TI  - [Osler's disease].
AB  - Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and
      Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal
      blood vessel formation in the skin, mucous membranes and often in organs, such as
      the lungs, liver and brain (arteriovenous malformations AVM). Various types are
      known. Patients may present with epistaxis. Teleangiectasia can be identified by
      visual inspection during physical examination of the skin or oral cavity or by
      endoscopy. Diagnosis is made after clinical examination and genetic testing based
      on the Curacao criteria. Modern imaging modalities, such as computed tomography
      (CT) or magnetic resonance imaging (MRI) have become more important as they can
      depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the
      use of a contrast agent while other locations including the central nervous
      system (CNS) usually require administration of contrast agents. Knowledge of
      possible clinical manifestations in various organs, possible complications and
      typical radiological presentation is mandatory to enable adequate therapy of
      these patients. Interventional procedures are becoming increasingly more
      important in the treatment of HHT patients. 

PMID- 24276215
TI  - [Tuberous sclerosis complex].
AB  - Tuberous sclerosis complex is an autosomal dominant disorder with variable
      affection of the central nervous system (CNS) and many other organ systems.
      Radiological features include various lesions of the brain as well as lesions of
      the lungs, kidneys and the heart. Imaging is important for the early detection of
      complications. This article provides an overview of the clinical features and
      therapy as well as the specific imaging of tuberous sclerosis complex. 

PMID- 24276216
TI  - Blood lead and cadmium levels and renal function in Korean adults.
AB  - BACKGROUND: The objective of this study was to evaluate the associations of blood
      lead and cadmium levels with estimated glomerular filtration rate (eGFR) and
      proteinuria in Korean adults. METHODS: This was a cross-sectional study based on
      the Korea Nation Health and Nutrition Examination Survey (KNHANES) to analyze the
      association of blood lead and cadmium levels with renal dysfunction and urine
      protein excretion. We defined renal dysfunction as eGFR < 60 ml/min/1.73 m(2), as
      measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation and proteinuria as positive urine dip-stick result. RESULTS: Blood lead
      and cadmium levels were significantly increased in the renal dysfunction group
      compared with the normal renal function group. Lead levels were significantly
      higher in the proteinuria group than in the group with no proteinuria. There were
      no differences in cadmium levels according to the amount of proteinuria.
      Multivariate logistic regression analysis adjusted for age and sex demonstrated
      higher lead and cadmium levels in the renal dysfunction group than in the group
      with normal renal function [odds ratio (OR) 1.344, 95 % confidence interval (CI)
      1.157-1.162, P < 0.05; OR 1.467, 95 % CI 1.077-1.999, P < 0.05, respectively].
      For proteinuria, the fully adjusted ORs comparing the highest versus the lowest
      lead and cadmium quartiles were 1.22 (95 % CI 1.00-1.50) and 0.51 (95 % CI 0.24
      1.08), respectively, showing no significance. For reduced eGFR, the fully
      adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles
      were 1.23 (95 % CI 0.98-1.53) and 1.93 (95 % CI 1.39-2.67), respectively, showing
      the significant association between lead and cadmium levels and renal function.
      The risk of having reduced eGFR for individuals in the highest quartiles of both
      lead and cadmium levels in blood was greater than for those in the highest
      quartile of blood level of lead or cadmium only. CONCLUSION: The CKD-EPI equation
      showed that blood lead and cadmium levels were associated with renal dysfunction
      in the Korean adult population. This finding has significant implications for
      environmental institutional strategies regarding heavy metal exposure.

PMID- 24276217
TI  - Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham
      Heart Study.
AB  - IMPORTANCE: In animal studies, brain-derived neurotrophic factor (BDNF) has been
      shown to impact neuronal survival and function and improve synaptic plasticity
      and long-term memory. Circulating BDNF levels increase with physical activity and
      caloric restriction, thus BDNF may mediate some of the observed associations
      between lifestyle and the risk for dementia. Some prior studies showed lower
      circulating BDNF in persons with Alzheimer disease (AD) compared with control
      participants; however, it remains uncertain whether reduced levels precede
      dementia onset. OBJECTIVE: To examine whether higher serum BDNF levels in
      cognitively healthy adults protect against the future risk for dementia and AD
      and to identify potential modifiers of this association. DESIGN, SETTING, AND
      PARTICIPANTS: Framingham Study original and offspring participants were followed
      up from 1992 and 1998, respectively, for up to 10 years. We used Cox models to
      relate BDNF levels to the risk for dementia and AD and adjusted for potential
      confounders. We also ran sensitivity analyses stratified by sex, age, and
      education, as well as related BDNF genetic variants to AD risk. This community
      based, prospective cohort study involved 2131 dementia-free participants aged 60
      years and older (mean [SD] age, 72 [7] years; 56% women). MAIN OUTCOMES AND
      MEASURES: Ten-year incidence of dementia and AD. RESULTS: During follow-up, 140
      participants developed dementia, 117 of whom had AD. Controlling for age and sex,
      each standard-deviation increment in BDNF was associated with a 33% lower risk
      for dementia and AD (P = .006 and P = .01, respectively) and these associations
      persisted after additional adjustments. Compared with the bottom quintile, BDNF
      levels in the top quintile were associated with less than half the risk for
      dementia and AD (hazard ratio, 0.49; 95% CI, 0.28-0.85; P = .01; and hazard
      ratio, 0.46; 95% CI, 0.24-0.86; P = .02, respectively). These associations were
      apparent only among women, persons aged 80 years and older, and those with
      college degrees (hazard ratios for AD: 0.65, [95% CI, 0.50-0.85], P = .001; 0.63
      [95% CI, 0.47-0.85], P = .002; and 0.27 [95% CI, 0.11-0.65], P = .003,
      respectively). Brain-derived neurotrophic factor genetic variants were not
      associated with AD risk. CONCLUSIONS AND RELEVANCE: Higher serum BDNF levels may
      protect against future occurrence of dementia and AD. Our findings suggest a role
      for BDNF in the biology and possibly in the prevention of dementia and AD,
      especially in select subgroups of women and older and more highly educated
      persons.

PMID- 24276218
TI  - Differential regulation of somatostatin receptor dephosphorylation by beta
      arrestin1 and beta-arrestin2.
AB  - Signaling of G protein-coupled receptors (GPCRs) is tightly regulated by
      coordinated phosphorylation of intracellular serine and threonine residues.
      Although the mechanisms of agonist-induced phosphorylation have been deciphered
      for many GPCRs, the regulation of their dephosphorylation remains poorly
      understood. Using a combination of siRNA knockdown screening and phosphosite
      specific antibodies, we have recently identified the catalytic subunit beta of
      protein phosphatase 1 (PP1beta) as major constituent of the GPCR phosphatase
      responsible for dephosphorylation of the sst2 somatostatin receptor. However, PP1
      targeting subunits specifically required for GPCR dephosphorylation have not been
      identified so far. Here, we show that siRNA knockdown of beta-arrestin1 strongly
      inhibits sst2 receptor dephosphorylation. Co-immunoprecipitation experiments
      demonstrate that beta-arrestin1 and PP1beta exist as constitutive complex that
      mediates rapid dephosphorylation of sst2 receptors at or near the plasma
      membrane. By contrast, beta-arrestin2 is not essential for rapid sst2 receptor
      dephosphorylation. Together, these findings reveal a novel scaffolding function
      of beta-arrestin1 that facilitates efficient targeting of PP1beta to
      phosphorylated GPCRs. 

PMID- 24276219
TI  - Adenylyl cyclase regulation in heart failure due to myocardial infarction in
      rats.
AB  - Cardiac adenylyl cyclase (AC) activity was described to be differentially
      regulated in left and right ventricles (LVs and RVs) of rats with heart failure
      (HF) due to LV myocardial infarction (MI) (Sethi et al. Am J Physiol 272:H884
      H893, 1997). AC activities in LVs and RVs were increased and decreased
      respectively in rats 8 and 16 weeks post MI under basal and stimulatory
      conditions including AC activation via beta-adrenergic receptors (beta-ARs),
      stimulatory G protein (Gs), and direct AC activation with forskolin (FS). The
      current study aimed to detect alterations in rat heart AC activities in a
      comparable model of HF 9 weeks post LV MI. Therefore, cardiac AC activities were
      measured under basal and beta-AR-, Gs-, or FS-stimulated conditions as well as
      under inhibition with various MANT [2'(3')-O-(N-methylanthraniloyl)]-nucleotide
      AC inhibitors and the P-site AC inhibitors NKY80 [2-amino-7-(2-furanyl)-7,8
      dihydro-5(6H)-quinazolinone] and vidarabine (9-beta-D-arabinosyladenine, AraAde).
      Basal and stimulated AC activities along with AC inhibition experiments did not
      reveal evidence for changes in AC activity in LVs and RVs from MI group animals
      despite the presence of congestive HF. However, our study is indeterminate.
      Further studies are required to identify the factors responsible for previously
      described changes in cardiac AC activity in MI induced HF and to elucidate the
      role of altered AC regulation in the pathophysiology of HF. In order to detect
      small changes in AC regulation, larger group sizes than the ones used in our
      present study are required. 

PMID- 24276221
TI  - The mechanisms and meaning of the mismatch negativity.
AB  - The mismatch negativity (MMN) is a pre-attentive auditory event-related potential
      (ERP) component that is elicited by a change in a repetitive acoustic pattern. It
      is obtained by subtracting responses evoked by frequent 'standard' sounds from
      responses evoked by infrequent 'deviant' sounds that differ from the standards
      along some acoustic dimension, e.g., frequency, intensity, or duration, or
      abstract feature. The MMN has been attributed to neural generators within the
      temporal and frontal lobes. The mechanisms and meaning of the MMN continue to be
      debated. Two dominant explanations for the MMN have been proposed. According to
      the "neural adaptation" hypothesis, repeated presentation of the standards
      results in adapted (i.e., attenuated) responses of feature-selective neurons in
      auditory cortex. Rare deviant sounds activate neurons that are less adapted than
      those stimulated by the frequent standard sounds, and thus elicit a larger
      'obligatory' response, which yields the MMN following the subtraction procedure.
      In contrast, according to the "sensory memory" hypothesis, the MMN is a 'novel'
      (non-obligatory) ERP component that reflects a deviation between properties of an
      incoming sound and those of a neural 'memory trace' established by the preceding
      standard sounds. Here, we provide a selective review of studies which are
      relevant to the controversy between proponents of these two interpretations of
      the MMN. We also present preliminary neurophysiological data from monkey auditory
      cortex with potential implications for the debate. We conclude that the
      mechanisms and meaning of the MMN are still unresolved and offer remarks on how
      to make progress on these important issues. 

PMID- 24276220
TI  - Learning to associate auditory and visual stimuli: behavioral and neural
      mechanisms.
AB  - The ability to effectively combine sensory inputs across modalities is vital for
      acquiring a unified percept of events. For example, watching a hammer hit a nail
      while simultaneously identifying the sound as originating from the event requires
      the ability to identify spatio-temporal congruencies and statistical
      regularities. In this study, we applied a reaction time and hazard function
      measure known as capacity (e.g., Townsend and AshbyCognitive Theory 200-239,
      1978) to quantify the extent to which observers learn paired associations between
      simple auditory and visual patterns in a model theoretic manner. As expected,
      results showed that learning was associated with an increase in accuracy, but
      more significantly, an increase in capacity. The aim of this study was to
      associate capacity measures of multisensory learning, with neural based measures,
      namely mean global field power (GFP). We observed a co-variation between an
      increase in capacity, and a decrease in GFP amplitude as learning occurred. This
      suggests that capacity constitutes a reliable behavioral index of efficient
      energy expenditure in the neural domain. 

PMID- 24276223
TI  - Effect of using repeated measurements of a Mediterranean style diet on the
      strength of the association with cardiovascular disease during 12 years: the
      Doetinchem Cohort Study.
AB  - BACKGROUND: In cohort studies, often only one baseline measurement of dietary
      intake is available. This may underestimate the strength of the association with
      cardiovascular diseases (CVD). OBJECTIVE: The main objective is to compare the
      strength of the association of a Mediterranean style diet with CVD using one
      baseline measurement of diet versus three repeated measurements over a 10-year
      period. DESIGN: We used dietary and lifestyle data of three rounds of the
      Doetinchem Cohort Study. At baseline, 7,769 persons aged 20-65 years were
      examined. Diet was assessed with a 178 item validated food-frequency
      questionnaire and operationalized with the Mediterranean Diet Score (MDS) ranging
      from 0 to 9. Cox proportional hazards models were used to estimate hazard ratios
      (HRs) and 95% confidence intervals (CI). Analyses were adjusted for age, sex, and
      repeated measurements of smoking, sports, total energy intake, and educational
      level. RESULTS: Comparing an MDS of >=5.5-9 to an MDS of 0-<3.5, baseline MDS was
      associated with a 23% lower risk [HR 0.77 (95% CI 0.53-1.11)] and the updated
      mean with a 35% lower risk [HR 0.65 (0.43-0.97)] of a composite of fatal CVD,
      nonfatal myocardial infarction, and stroke (composite CVD). For fatal CVD,
      baseline MDS was associated with a 13% lower risk [HR 0.87 (0.36-2.07)] and the
      updated mean with a 56% lower risk [HR 0.44 (0.19-1.05)]. CONCLUSION: The
      strength of the association between a Mediterranean style diet and CVD is likely
      underestimated because most studies so far used only one baseline measurement.

PMID- 24276222
TI  - The alpha' subunit of beta-conglycinin and the A1-5 subunits of glycinin are not
      essential for many hypolipidemic actions of dietary soy proteins in rats.
AB  - PURPOSE: This study examined the effects of dietary soy protein (SP) lacking
      different storage protein subunits and isoflavones (ISF) on the abdominal fat,
      blood lipids, thyroid hormones, and enzymatic activities in rats. METHODS:
      Weanling Sprague-Dawley rats (8 males and 8 females/group) were fed diets
      containing either 20 % casein without or with supplemental isoflavones or alcohol
      washed SP isolate or SP concentrates (SPC) prepared from 6 different soy bean
      lines for 8 weeks. RESULTS: Feeding of diets containing SPC regardless of their
      subunit compositions significantly lowered relative liver weights, blood total,
      free, and LDL cholesterol in both genders (P < 0.05) and also reduced serum free
      fatty acids (FFA) and abdominal fat in females (P < 0.05) compared to the casein
      or casein + ISF diets. Dietary SPC significantly elevated the plasma free
      triiodothyronine (T3) in both genders and total T3 in females compared to the
      casein diet (P < 0.05). The SPC lacking beta-conglycinin alpha' and either the
      glycinin A1-3 or A1-5 subunits increased total T3 in males and reduced plasma
      enzymatic activities of creatine kinase and lactate dehydrogenase compared to
      casein or casein + ISF diet (P < 0.05). CONCLUSIONS: Soy isoflavones were mainly
      responsible for the hypocholesterolemic effects and increased plasma free T3,
      whereas reduction in FFA, abdominal fat, liver weight and increased plasma total
      T3 were the effects of the soy proteins. Neither the alpha' subunit of beta
      conglycinin nor the A1-5 subunits of glycinin are essential for the hypolipidemic
      properties of soy proteins.

PMID- 24276225
TI  - Can turned inward patella predict an excess of femoral anteversion during gait in
      spastic diplegic children?
AB  - BACKGROUND: Determining patellar orientation in the transverse plane during
      observational gait analysis is a fundamental aspect of physical examinations.
      Many physicians consider that an abnormal position of the patella in the
      transverse planes is only explained by a rotational abnormality of the proximal
      femur. METHODS: A total of 188 spastic diplegic children with cerebral palsy were
      reviewed (376 lower limbs). The physical examination included observation of
      patellar orientation at midstride and measuring femoral anteversion (FA). All
      patients also underwent 3-dimensional (3D) computerized gait analysis of pelvic
      and hip rotation kinematics. RESULTS: Observational gait analysis and videotapes
      found 103 children (206 lower limbs) with inturned patella at midstance.
      Kinematic data from 3D gait analysis showed that the visual impression of turned
      inward patella was erroneous in 48 limbs. Of the remaining 158 lower limbs, 117
      (74%) exhibited excessive FA and 41 (26%) did not. Of the 117 with excessive FA,
      kinematics showed only 66 (56%) with excessive internal hip rotation (with or
      without excessive internal pelvic rotation). Of the 41 lower limbs without
      excessive FA, 25 were explained by excessive internal pelvic rotation and 16 were
      explained by excessive internal hip rotation (isolated spasticity and/or
      contracture of internal rotator muscles). Turned inward patella was caused by
      isolated excessive internal pelvic rotation in 48%, excessive internal hip
      rotation in 35% (including 44 cases with excessive FA and 12 cases with isolated
      spasticity and/or contracture of internal hip rotators), and excessive internal
      hip rotation combined with excessive internal pelvic rotation in 17%.
      CONCLUSIONS: Excessive FA was not the only cause of turned inward patella gait
      and could not explain this gait anomaly by itself. Excessive internal pelvic
      rotation was the most frequent cause of turned inward patella gait. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24276224
TI  - Pubertal supplementation of lipotropes in female rats reduces mammary cancer risk
      by suppressing histone deacetylase 1.
AB  - PURPOSE: The time from puberty to the first pregnancy is known to be important
      for a woman's life-time breast cancer risk. Recent studies suggest that
      epigenetic mechanisms may involve pubertal maturation processes, which can affect
      the risk of breast cancer in later life. Epigenetic alterations are related to
      lipotropes (methionine, choline, folate, and vitamin B12), which are methyl
      donors and cofactors. However, the effects of pubertal supplementation of
      lipotropes in breast cancer remain largely unknown. METHODS: Twenty female
      Sprague-Dawley rats, aged 6 weeks, were divided into two groups and fed a normal
      control diet or a lipotrope-fortified diet formulated to provide five times basal
      levels of lipotropes during puberty. All rats were injected intraperitoneally
      with N-nitroso-N-methylurea at 50 days of age to induce mammary tumors. RESULTS:
      Tumor multiplicity and tumor volume decreased significantly as a result of
      lipotrope supplementation. Interestingly, quantitative RT-PCR revealed
      significantly decreased expression of histone deacetylase 1 (Hdac1) and DNA
      methyltransferase 1 (Dnmt1) genes in tumor tissues of the rats supplemented with
      lipotrope-fortified diet, suggesting that reduced risk of breast cancer can be
      attributed, at least in part, to decreased expression of these two genes.
      CONCLUSIONS: This study demonstrates that supplementation of lipotrope-fortified
      diet during puberty suppresses tumor growth, potentially through down-regulating
      Hdac1 and Dnmt1 gene expression. Our findings suggest that pubertal methyl diet
      plays an important role in the etiology of breast cancer, and further studies are
      warranted to develop preventative strategies against breast cancer.

PMID- 24276226
TI  - The medial epicondyle-ulnar nerve relation with various elbow positions in
      healthy children.
AB  - BACKGROUND: The position of the ulnar nerve relative to the medial epicondyle in
      healthy children was determined with a high-resolution ultrasonography with elbow
      flexion, forearm pronation, and supination maneuvers which are commonly employed
      during reduction of the supracondylar humerus fractures. METHODS: Healthy
      children aged between 4 and 12 years were enrolled in this study. Both elbows of
      the children were evaluated with a high-resolution sonography device with gradual
      flexion of the elbow, whereas the forearm is alternately in pronation and
      supination. The medial epicondyle-ulnar nerve distance was measured with the
      various positions of the elbow and the forearm. One-way analysis of variance was
      used to analyze the differences of medial epicondyle-ulnar nerve distance at
      different elbow flexion angles and forearm supination-pronation positions. Paried
      t test was used to compare the differences between the age and sex of the
      children. RESULTS: Twelve female and 26 male children (76 elbows) with a mean age
      of 8.36 years were included in the study. Ulnar nerve was translated anteriorly
      through the medial epicondyle with increasing elbow flexion. The mean medial
      epicondyle-ulnar nerve distance that was 3.7 mm in an extended elbow decreased to
      1.1 mm with full elbow flexion. The difference was statistically significant
      (P<0.0001). Presence of the forearm in either supination or pronation did not
      produce a statistically significant difference. The age and sex of the children
      did not produce a statistically significance difference in medial epicondyle
      ulnar nerve distance. CONCLUSIONS: Flexion of the elbow brings the ulnar nerve to
      a close proximity to the medial epicondyle independent of forearm pronation and
      supination in healthy children. The decrement of the medial epicondyle-ulnar
      nerve distance up to 1.1 mm in a fully flexed elbow might be a factor that
      endangers the nerve during medial pinning in supracondylar humerus fractures.
      LEVEL OF EVIDENCE: Level I-diagnostic studies.

PMID- 24276227
TI  - Percutaneous correction of persistent severe metatarsus adductus in children.
AB  - BACKGROUND: Percutaneous techniques for the correction of foot deformities are
      gaining popularity in the adult population, but remain poorly explored in
      children. Of the several surgical techniques described to treat persistent severe
      metatarsus adductus (MA) deformity in children, neither was percutaneous. The
      purpose of the study was to describe a percutaneous technique for MA correction
      in children, to report the outcomes, and to discuss the advantages it offers.
      METHODS: We designed a prospective study on 34 consecutive feet with MA deformity
      from 26 children undergoing percutaneous correction. All operated feet had
      severe, rigid MA deformities, most of which were components of residual/recurrent
      clubfoot deformities. The mean age at surgery was 5.7 years and the mean follow
      up was 55.2 months. For clinical evaluation, we used the bisector method; the
      first cuneometatarsal angle and metatarsal-metaphyseal angle measured in weight
      bearing radiographs and AOFASf score were determined preoperatively and
      postoperatively. In unilateral cases, we used the contralateral foot measurements
      as control. The operating time and the hospitalization time were also recorded.
      The surgical technique consisted of performing the Cahuzac procedure for MA
      correction with a percutaneous approach. RESULTS: At the final follow-up all feet
      presented a normal heel bisector line. Radiologic parameters were normalized when
      compared with control feet. The mean surgical and hospitalization time was 14
      minutes and 6 hours, respectively. Mean AOFAS score improved from 78 to 98.
      CONCLUSIONS: A minimally invasive percutaneous technique allowed a successful
      correction of MA deformity in children and resulted in a substantive decrease in
      both surgical and hospitalization time and better cosmetic results. LEVEL OF
      EVIDENCE: Level II.

PMID- 24276228
TI  - The quality of pediatric orthopaedic information on the internet.
AB  - BACKGROUND: Many patients use the Internet for health information. However, there
      are few guarantees to the reliability and accuracy of this information. This
      study examined the quality and content of the Internet Web pages for 10 common
      pediatric orthopaedic diagnoses. METHODS: We identified 10 common diagnoses in
      pediatric orthopaedics: brachial plexus injury, cerebral palsy, clubfoot,
      developmental dysplasia of the hip, leg length discrepancy, osteochondroma,
      polydactyly, scoliosis, spina bifida, and syndactyly. We used 2 of the most
      popular search engines to identify the top 10 Web sites for each disease. We
      evaluated the Web sites utilizing both the quality-based Health On the Net (HON)
      Foundation criteria and our own content-based grading sheets. The custom grading
      sheets focused on essential information about disease summary, pathogenesis,
      diagnosis, treatment, and prognosis. RESULTS: Three orthopaedic surgeons graded
      98 academic, commercial, nonprofit, and physicians' Web sites for 10 diseases.
      Academic Web sites scored the highest in content (mean, 60.8% +/- 15.5%), whereas
      commercial Web sites scored the lowest (mean, 46.7% +/- 22.2%). Among the
      diagnoses, osteochondroma Web sites had the highest content scores (mean, 75.8%
      +/- 11.8%), whereas polydactyly Web sites had the lowest content scores (mean,
      39.3% +/- 15.7%). In contrast, Web sites about developmental dysplasia of the hip
      had the highest HON scores (65.0 +/- 11.1), whereas those about brachial plexus
      birth palsy scored the lowest (42.6% +/- 16.9%). Among the content subgroups,
      scores were generally higher for disease summary and diagnostics and lower for
      prognosis. CONCLUSIONS: The Internet Web sites reviewed demonstrated a wide range
      of content and information. We found that nonprofit and academic Web sites were
      the most reliable sources, whereas commercial and, surprisingly, physician-run
      Web sites were the least reliable. We advise physicians to talk to their patients
      about the information they get on the Internet and how it dictates their
      expectations. We hope this study, combined with further understanding of how our
      patients use this information, can help improve the Internet content. CLINICAL
      RELEVANCE: Physicians should know that their patients may be receiving misleading
      information from the Internet and be able to discuss this with their patients.

PMID- 24276229
TI  - Absence of radiographic abnormalities in nursemaid's elbows.
AB  - BACKGROUND: Disagreement exists between physicians on the usefulness of a
      prereduction radiograph for diagnosis and treatment of nursemaid's elbows in
      children. Some evidence suggests that nursemaid's elbows have identifying
      features on radiographs. This study compares the radiographs of nursemaid's
      elbows to normal, control elbows in children and hypothesizes that
      differentiating features do not exist on radiograph. METHODS: For this
      retrospective case-control study, hospital billing records were searched to
      identify all patients under age 6 treated with closed reduction for a nursemaid's
      elbow between November 2005 and October 2009. Twenty-seven nursemaid's elbows
      were age-matched and sex-matched to 27 normal "comparison view," control elbows.
      Radiocapitellar line offset, proximal radial length, anterior fat pad angle, and
      visibility of the posterior fat pad were measured on the radiographs by 2 raters.
      Their interrater reliability was assessed with intraclass correlations, and the
      nursemaid's and control elbow measures were compared using Wilcoxon tests.
      RESULTS: Nursemaid's elbows and healthy control elbows did not differ
      significantly in offset of the radiocapitellar line from the capitellum center on
      anteroposterior (P=0.49) or lateral views (P=0.67), in proximal radial length
      (P=0.95), anterior fat pad angle (P=0.49), or posterior fat pad visibility
      (P=1.00) on lateral views. CONCLUSIONS: Nursemaid's elbows are indistinguishable
      from healthy elbows on radiograph. Thus, the term "radial head subluxation"
      appears to be a misnomer, and prereduction radiographs should only be used to
      eliminate the possibility of fracture. From a radiologic perspective, nursemaid's
      elbows remain a diagnosis of exclusion. LEVEL OF EVIDENCE: Therapeutic Level III
      retrospective comparative study.

PMID- 24276230
TI  - Efficacy of nonfusion treatment for subacute and chronic atlanto-axial rotatory
      fixation in children.
AB  - BACKGROUND: Historical guidelines suggest limited efficacy for nonfusion
      treatment of chronic atlanto-axial rotatory subluxation/fixation (AARF). Surgical
      fusion has potential side effects; therefore, it is important to understand the
      role for nonfusion treatment of chronic AARF. This case series examines the
      success rate of nonfusion treatment. METHODS: A key word search was used to
      identify all patients with AARF with delayed presentation of >= 4 weeks. Fifteen
      patients met study inclusion criteria and had adequate clinical information for
      review. Data collected included age, sex, delay in presentation, mechanism of
      injury, severity of subluxation (Fielding classification), treatment, follow-up,
      and clinical information at latest follow-up. RESULTS: There were 11 girls and 3
      boys with an average age of 7.2 years (range, 1.5 to 12 years). Initial treatment
      of 3 patients included fusion. Eleven patients were initially treated without
      fusion. Eight of these 11 patients were successfully reduced with either halter
      traction, halo gravity traction, and noninvasive halo or halo vest, and reduction
      was maintained without fusion (73%) at 10.3 years follow-up. Three patients (27%)
      experienced recurrence of AARF at an average time of 2 weeks (range, 0 to 4 wk)
      and were treated with fusion. Average delay in presentation for all patients was
      18 weeks (range, 4 to 92 wk), whereas it was 6 weeks and 9.3 weeks in those
      successfully treated without fusion and in those who failed nonfusion treatment,
      respectively. Age, delay in presentation, and underlying diagnosis were similar
      for fusion and nonfusion groups. CONCLUSIONS: Although AARF may recur after a
      trial of reduction and nonfusion treatment, pediatric patients with delayed
      presentation (>1 month) of AARF may be treated with an initial trial of nonfusion
      treatment. Parents should be counseled about the risk of recurrence and possible
      need for ultimate fusion. LEVEL OF EVIDENCE: Level III, therapeutic retrospective
      comparative study.

PMID- 24276231
TI  - Medial approach for drainage of the obturator musculature in children.
AB  - BACKGROUND: In a recent study designed to determine the anatomic location of
      infection in children presenting with acute hip pain, fever, and elevated
      inflammatory markers, we demonstrated the incidence of infection of the
      musculature surrounding the hip to be greater than twice that of septic
      arthritis. Importantly, the obturator musculature was infected in >60% of cases.
      Situated deep in the pelvis, surrounding the obturator foramen, debridement of
      these muscles and placement of a drain traditionally requires an extensive
      ilioinguinal or Pfannenstiel approach, placing significant risk to the
      surrounding neurovascular structures. We hypothesized that the obturator internus
      and externus could be successfully debrided using a limited medial approach.
      METHODS: An IRB-approved prospective study of children (0 to 18 y) evaluated in
      the pediatric emergency department by an orthopaedic surgeon to rule out septic
      hip arthritis at a tertiary care children's hospital (July 1, 2010 to June 30,
      2012) was conducted. Infected obturator musculature was identified and confirmed
      using magnetic resonance imaging. Cadaveric dissection was performed comparing
      the ilioinguinal, Pfannenstiel, and proposed minimally invasive medial approach.
      The proposed approach was utilized to debride and place drains in 7 consecutive
      patients. RESULTS: Anatomic information gained from magnetic resonance images of
      patients with abscess within the obturator musculature, and from the results of
      cadaveric studies, allowed for planning of a novel surgical approach. We found
      that through the surgical approach used to perform an osteotomy of the ischium
      (Tonnis) the obturator externus could be debrided through the adductor brevis and
      the obturator internus could be debrided through the obturator foramen. Using our
      medial approach, resolution of symptoms in all children who underwent surgical
      drainage resulted without complication. CONCLUSIONS: Our medial approach can
      safely access the obturator musculature for abscess decompression and drain
      placement with successful results. Advantages to this approach include: lower
      risk to neurovascular structures within the pelvis, less soft tissue trauma, and
      similarity to current techniques used for adductor lengthening, medial reduction
      of the dislocated hip, and osteotomy of the ischium. LEVEL OF EVIDENCE: Level II.

PMID- 24276233
TI  - Structural relationships among LiNaMg[PO4]F and Na2M[PO4]F (M = Mn-Ni, and Mg),
      and the magnetic structure of LiNaNi[PO4]F.
AB  - The new compound LiNaMg[PO4]F has been synthesized by a wet chemical reaction
      route. Its crystal structure was determined from single-crystal X-ray diffraction
      data. LiNaMg[PO4]F crystallizes with the monoclinic pseudomerohedrally twinned
      LiNaNi[PO4]F structure, space group P2(1)/c, a = 6.772(4), b = 11.154(6), c =
      5.021(3) A, beta = 90.00(1) degrees  and Z = 4. The structure contains [MgO3F]n
      chains made up of zigzag edge-sharing MgO4F2 octahedra. These chains are
      interlinked by PO4 tetrahedra forming 2D-Mg[PO4]F layers. The alkali metal atoms
      are well ordered in between these layers over two atomic positions. The use of
      group-subgroup transformation schemes in the Barnighausen formalism enabled us to
      determine precise phase transition mechanisms from LiNaNi[PO4]F- to Na2M[PO4]F
      type structures (M = Mn-Ni, and Mg) (see video clip 1 and 2). The crystal and
      magnetic structure and properties of the parent LiNaNi[PO4]F phase were also
      studied by magnetometry and neutron powder diffraction. Despite the rather long
      interlayer distance, d(min)(Ni(+2)-Ni(+2)) ~ 6.8 A, the material develops a long
      range magnetic order below 5 K. The magnetic structure can be viewed as
      antiferromagnetically coupled ferromagnetic layers with moments parallel to the b
      axis.

PMID- 24276232
TI  - Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48
      containing lipoprotein in ApoE-deficient mice.
AB  - Individuals carrying mutations at both ataxia telangiectasia mutated (ATM) gene
      alleles reportedly have increased plasma cholesterol and triglyceride levels.
      Previous studies have demonstrated that defective ATM function promotes
      atherosclerosis. We previously demonstrated that ATM facilitates the clearance of
      plasma apolipoprotein (Apo)E-deficient, ApoB48-containing (E(-)/B(48))
      lipoproteins in ApoE-deficient mice (ApoE(-/-) mice). However, to date there is
      no exact explanation available as to the mechanism(s) through which ATM is
      involved in the removal of E(-)/B(48) lipoprotein in ApoE(-/-) mice. In this
      study, to our knowledge, we demonstrate for the first time that heterozygous ATM
      mutation reduces the hepatocyte uptake of E(-)/B(48) lipoproteins in ApoE(-/-)
      mice; however, heterozygous ATM mutation did not affect hepatocyte binding to E(
      )/B(48) lipoproteins. Moreover, our results revealed that ATM proteins were
      localized in the nucleus, early endosomes and late endosomes, but not in the
      plasma membrane in the hepatocytes of ApoE(-/-) mice. In addition, following
      treatment with the ATM activator, chloroquine, and E(-)/B(48) lipoproteins, ATM
      interacted with class III phosphatidylinositol-3-kinases (PI3Ks) and the
      activated ATM protein enhanced class III PI3K activity. Furthermore, treatment
      with a class III PI3K inhibitor (LY290042 and 3-MA) attenuated the intracellular
      total cholesterol accumulation induced by ATM activation. These results provide
      insight into the mechanisms behind the involvment of ATM in the process of
      endocytosis of E(-)/B(48) lipoprotein in ApoE(-/-) mice, demonstrating the role
      of class III PI3K protein.

PMID- 24276234
TI  - A new strategy to enhance low-temperature capacitance: combination of two charge
      storage mechanisms.
AB  - By combining two pseudocapacitance charge-storage mechanisms occurring on the
      electrode and in the electrolyte, respectively, the specific capacitance of NiO
      at -20  degrees C in an alkaline electrolyte containing Fe(CN)6(3-)/Fe(CN)6(4-)
      couple increases twice, superior to the level at room temperature. 

PMID- 24276235
TI  - Complete genome sequence of a new begomovirus associated with yellow mosaic
      disease of Hemidesmus indicus in India.
AB  - The complete DNA A genome of a virus isolate associated with yellow mosaic
      disease of a medicinal plant, Hemidesmus indicus, from India was cloned and
      sequenced. The length of DNA A was 2825 nucleotides, 35 nucleotides longer than
      the unit genome of monopartite begomoviruses. Comparison of the nucleotide
      sequence of DNA A of the virus isolate with those of other begomoviruses showed
      maximum sequence identity of 69 % to DNA A of ageratum yellow vein China virus
      (AYVCNV; AJ558120) and 68 % with tomato yellow leaf curl virus- LBa4 (TYLCV;
      EF185318), and it formed a distinct clade in phylogenetic analysis. The genome
      organization of the present virus isolate was found to be similar to that of Old
      World monopartite begomoviruses. The genome was considered to be monopartite,
      because association of DNA B and beta satellite DNA components was not detected.
      Based on its sequence identity (<70 %) to all other begomoviruses known to date
      and ICTV (International Committee on Taxonomy of Viruses) species demarcating
      criteria (<89 % identity), it is considered a member of a novel begomovirus
      species, and the tentative name "Hemidesmus yellow mosaic virus" (HeYMV) is
      proposed.

PMID- 24276236
TI  - Induction of chemokines and cytokines before neutrophils and macrophage
      recruitment in different regions of rat liver after TAA administration.
AB  - Single-dose thioacetamide (TAA) administration induces inflammation and acute
      liver damage. The mechanism of inflammatory cell recruitment in the liver is
      still unclear. The aim of this study was to examine the sequence and recruitment
      of inflammatory cells in different liver regions in relation to CXC- and CC
      chemokine and cytokine expression during acute liver injury. Single-dose TAA was
      administered to rats intraperitoneally, and animals were killed at different time
      points thereafter. Serum and liver tissue were taken and frozen immediately.
      Tissue was used for immunostaining cryostat sections, RNA, and protein
      extraction. RT-PCR and western blotting were performed for RNA and protein
      analysis, respectively. An early increase (3 h) in CXCL8/IL-8 levels was measured
      followed by a marked release in MCP1/CCL2 (24 h) serum levels after TAA
      administration compared with controls. Similarly, an early increase in specific
      RNA of hepatic chemokines CXCL1/KC and CXCL8/IL-8 was found at 3 h, followed by
      an upregulation of CXCL5/LIX (6 h), CXCL2/MIP-2 (12 h), and MCP1/CCL2 gene
      expression at 24-48 h. Further, an induction of pro-inflammatory cytokines IFN
      gamma and IL-1beta followed by IL-6 and TNF-alpha was observed with a maximum at
      12 h. The magnitude of increase in gene expression of TNF-alpha and MCP1/CCL2 was
      the highest among all cytokines and chemokines, respectively. By means of
      immunohistochemistry, an early (12-24 h) increase in the number of only
      neutrophil granulocytes (NGs) attached to and around portal vessel walls was
      observed, followed by increased numbers of mononuclear phagocytes (24-48 h) along
      the sinusoids. Treatment of the human monocytic cell line U-937 with TNF-alpha
      increased the gene expression of CXCL1/KC, CXCL8/IL-8, and MCP1/CCL2. Conversely,
      adding of infliximab (IFX) to the culture medium inhibited this upregulation
      significantly. In conclusion, single-dose TAA administration induces a sequence
      of events with a defined upregulation of gene expression of inflammatory
      chemokines and cytokines and a transient accumulation of NGs within the portal
      area and macrophages along the sinusoids throughout the liver. Periportal
      inflammation seems to precede hepatocellular damage. 

PMID- 24276237
TI  - MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERalpha)
      positive mammary adenocarcinomas.
AB  - Separase, a protease encoded by the ESPL1 gene, cleaves the chromosomal cohesin
      during mitosis. Separase protein and transcripts are overexpressed in a wide
      range of human cancers. To investigate the physiological consequence of Separase
      overexpression in animals, we have generated a transgenic MMTV-Espl1 mouse model
      that overexpresses Separase protein in the mammary glands. MMTV-Espl1 mice in a
      C57BL/6 genetic background develop aggressive, highly aneuploid and estrogen
      receptor alpha-positive (ERalpha+) mammary adenocarcinomas with an 80%
      penetrance. The mammary tumors caused by overexpression of Separase, alone or
      combined with p53 heterozygosity, in mammary epithelium mimic several aspects of
      the most aggressive forms of human breast cancer, including high levels of
      genetic instability, cell cycle defects, poor differentiation, distant metastasis
      and metaplasia. Histopathologically, MMTV-Espl1 tumors are highly heterogeneous
      showing features of both luminal as well as basal subtypes of breast cancers,
      with aggressive disease phenotype. In addition to aneuploidy, Separase
      overexpression results in chromosomal instability (CIN) including premature
      chromatid separation (PCS), lagging chromosomes, anaphase bridges, micronuclei,
      centrosome amplification, multinucleated cells, gradual accumulation of DNA
      damage and progressive loss of tumor suppressors p53 and cadherin gene loci.
      These results suggest that Separase-overexpressing mammary cells are not only
      susceptible to chromosomal missegregation-induced aneuploidy but also other
      genetic instabilities including DNA damage and loss of key tumor suppressor gene
      loci, which in combination can initiate tumorigenesis and disease progression. 

PMID- 24276238
TI  - Scrib heterozygosity predisposes to lung cancer and cooperates with KRas
      hyperactivation to accelerate lung cancer progression in vivo.
AB  - Lung cancer is the leading cause of cancer deaths worldwide with non small-cell
      lung cancer (NSCLC) accounting for 80% of all lung cancers. Although activating
      mutations in genes of the RAS-MAPK pathway occur in up to 30% of all NSCLC, the
      cooperating genetic lesions that are required for lung cancer initiation and
      progression remain poorly understood. Here we identify a role for the cell
      polarity regulator Scribble (Scrib) in NSCLC. A survey of genomic databases
      reveals deregulation of SCRIB in human lung cancer and we show that Scrib(+/-)
      mutant mice develop lung cancer by 540 days with a penetrance of 43%. To model
      NSCLC development in vivo, we used the extensively characterized LSL-KRas(G12D)
      murine model of NSCLC. We show that loss of Scrib and activated oncogenic KRas
      cooperate in vivo, resulting in more aggressive lung tumors, likely due to a
      synergistic elevation in RAS-MAPK signaling. Finally, we provide data consistent
      with immune infiltration having an important role in the acceleration of
      tumorigenesis in KRas(G12D) lung tumors following Scrib loss. 

PMID- 24276239
TI  - Low CHD5 expression activates the DNA damage response and predicts poor outcome
      in patients undergoing adjuvant therapy for resected pancreatic cancer.
AB  - The DNA damage response (DDR) promotes genome integrity and serves as a cancer
      barrier in precancerous lesions but paradoxically may promote cancer survival.
      Genes that activate the DDR when dysregulated could function as useful biomarkers
      for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer
      cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced,
      activates the DDR. We evaluated the relationship of CHD5 expression with DDR
      activation in human pancreatic cancer cells and the association of CHD5
      expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by
      immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5
      expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and
      CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier
      log-rank survival analysis, patients with low CHD5 expression had a median
      recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5
      expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5
      expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and
      overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox
      regression analysis, low CHD5 expression remained associated with worse OS (HR:
      3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy.
      Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients
      with resected PAC receiving adjuvant chemotherapy. Our findings support a model
      in which dysregulated expression of tumor suppressor genes that induce DDR
      activation can be utilized as biomarkers for poor outcome.

PMID- 24276240
TI  - SALL4, a novel marker for human gastric carcinogenesis and metastasis.
AB  - SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal
      and pluripotency, has been suggested to be involved in tumorigenesis. The role of
      SALL4 in human gastric cancer, however, remains largely unknown. In this study,
      we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein
      levels in human gastric cancer tissues, and SALL4 level was highly correlated
      with lymph node metastasis. Enforced expression of SALL4 enhanced the
      proliferation and migration of human gastric cancer cells, whereas knockdown of
      SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression
      promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4
      overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer
      cells, with increased expression of Twist1, N-cadherin and decreased expression
      of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric
      cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our
      findings indicate that SALL4 has oncogenic roles in gastric cancer through the
      modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human
      gastric cancer diagnosis and therapy. 

PMID- 24276241
TI  - cIAP1 regulates TNF-mediated cdc42 activation and filopodia formation.
AB  - Tumour necrosis factor-alpha (TNF) is a cytokine endowed with multiple functions,
      depending on the cellular and environmental context. TNF receptor engagement
      induces the formation of a multimolecular complex including the TNFR-associated
      factor TRAF2, the receptor-interaction protein kinase RIP1 and the cellular
      inhibitor of apoptosis cIAP1, the latter being essential for NF-kappaB
      activation. Here, we show that cIAP1 also regulates TNF-induced actin
      cytoskeleton reorganization through a cdc42-dependent, NF-kappaB-independent
      pathway. Deletion of cIAP1 prevents TNF-induced filopodia and cdc42 activation.
      The expression of cIAP1 or its E3-ubiquitin ligase-defective mutant restores the
      ability of cIAP1(-/-) MEFs to produce filopodia, whereas a cIAP1 mutant unable to
      bind TRAF2 does not. Accordingly, the silencing of TRAF2 inhibits TNF-mediated
      filopodia formation, whereas silencing of RIP1 does not. cIAP1 directly binds
      cdc42 and promotes its RhoGDIalpha-mediated stabilization. TNF decreases cIAP1
      cdc42 interaction, suggesting that TNF-induced recruitment of cIAP1/TRAF2 to the
      receptor releases cdc42, which in turn triggers actin remodeling. cIAP1 also
      regulates cdc42 activation in response to EGF and HRas-V12 expression. A
      downregulation of cIAP1 altered the cell polarization, the cell adhesion to
      endothelial cells and cell intercalation, which are cdc42-dependent processes.
      Finally, we demonstrated that the deletion of cIAP1 regulated the HRas-V12
      mediated transformation process, including anchorage-dependent cell growth,
      tumour growth in a xenograft model and the development of experimental metastasis
      in the lung. 

PMID- 24276242
TI  - Distinct cellular origin and genetic requirement of Hedgehog-Gli in postnatal
      rhabdomyosarcoma genesis.
AB  - Dysregulation of the Hedgehog (Hh)-Gli signaling pathway is implicated in a
      variety of human cancers, including basal cell carcinoma (BCC), medulloblastoma
      (MB) and embryonal rhabdhomyosarcoma (eRMS), three principle tumors associated
      with human Gorlin syndrome. However, the cells of origin of these tumors,
      including eRMS, remain poorly understood. In this study, we explore the cell
      populations that give rise to Hh-related tumors by specifically activating
      Smoothened (Smo) in both Hh-producing and -responsive cell lineages in postnatal
      mice. Interestingly, we find that unlike BCC and MB, eRMS originates from the
      stem/progenitor populations that do not normally receive active Hh signaling.
      Furthermore, we find that the myogenic lineage in postnatal mice is largely Hh
      quiescent and that Pax7-expressing muscle satellite cells are not able to give
      rise to eRMS upon Smo or Gli1/2 overactivation in vivo, suggesting that Hh
      induced skeletal muscle eRMS arises from Hh/Gli quiescent non-myogenic cells. In
      addition, using the Gli1 null allele and a Gli3 repressor allele, we reveal a
      specific genetic requirement for Gli proteins in Hh-induced eRMS formation and
      provide molecular evidence for the involvement of Sox4/11 in eRMS cell survival
      and differentiation. 

PMID- 24276243
TI  - PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes
      tumorigenesis through activation of PI3K/AKT signaling.
AB  - Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements
      or abnormal transcription in many human cancers. Although multiple gastric cancer
      genomes have been sequenced, the driving recurrent gene fusions have not been
      well characterized. Here, we used paired-end transcriptome sequencing to identify
      novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary
      human gastric cancer tissues and their adjacent normal tissues. Multiple samples
      revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B
      STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion
      transcript was detected in 21.3% of primary human gastric cancers but not in
      adjacent matched normal gastric tissues. Based on reverse transcription PCR
      analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B
      STARD3 appears to be generated by RNA processing without chromosomal
      rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased
      cell proliferation and colony formation. This increased proliferation was
      mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling.
      Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor
      growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B
      STARD3 fusion transcript has a key role in subsets of gastric cancers through the
      activation of PI3K/AKT signaling. 

PMID- 24276245
TI  - E2F1 drives chemotherapeutic drug resistance via ABCG2.
AB  - Multidrug resistance is a major barrier against successful chemotherapy, and this
      has been shown in vitro to be often caused by ATP-binding cassette (ABC)
      transporters. These transporters are frequently overexpressed in human cancers
      and confer an adverse prognosis in many common malignancies. The genetic factors,
      however, that initiate their expression in cancer are largely unknown. Here we
      report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and
      specifically activated by the transcription factor E2F1--a factor perturbed in
      the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell
      systems, and, importantly, we have identified a significant correlation between
      elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1
      causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2.
      Furthermore, the E2F1-ABCG2 axis suppresses chemotherapy-induced cell death that
      can be restored by the inhibition of ABCG2. These findings therefore identify a
      new axis in multidrug resistance and highlight a radical new function of E2F1
      that is relevant to tumor therapy.

PMID- 24276244
TI  - Selective roles of E2Fs for ErbB2- and Myc-mediated mammary tumorigenesis.
AB  - Previous studies have demonstrated that cyclin D1, an upstream regulator of the
      Rb/E2F pathway, is an essential component of the ErbB2/Ras (but not the Wnt/Myc)
      oncogenic pathway in the mammary epithelium. However, the role of specific E2fs
      for ErbB2/Ras-mediated mammary tumorigenesis remains unknown. Here, we show that
      in the majority of mouse and human primary mammary carcinomas with ErbB2/HER2
      overexpression, E2f3a is up-regulated, raising the possibility that E2F3a is a
      critical effector of the ErbB2 oncogenic signaling pathway in the mammary gland.
      We examined the consequence of ablating individual E2fs in mice on ErbB2
      triggered mammary tumorigenesis in comparison to a comparable Myc-driven mammary
      tumor model. We found that loss of E2f1 or E2f3 led to a significant delay in
      tumor onset in both oncogenic models, whereas loss of E2f2 accelerated mammary
      tumorigenesis driven by Myc-overexpression. Furthermore, southern blot analysis
      of final tumors derived from conditionally deleted E2f3(-/loxP) mammary glands
      revealed that there is a selection against E2f3(-/-) cells from developing
      mammary carcinomas, and that such selection pressure is higher in the presence of
      ErbB2 activation than in the presence of Myc activation. Taken together, our data
      suggest oncogenic activities of E2F1 and E2F3 in ErbB2- or Myc-triggered mammary
      tumorigenesis, and a tumor suppressor role of E2F2 in Myc-mediated mammary
      tumorigenesis. 

PMID- 24276246
TI  - Phosphatidylethanolamine-binding protein 4 is associated with breast cancer
      metastasis through Src-mediated Akt tyrosine phosphorylation.
AB  - Metastasis is responsible for more than 90% of the mortality observed among
      patients with breast cancer. Human phosphatidylethanolamine-binding protein 4
      (hPEBP4) is a novel member of the PEBP family and functions as an anti-apoptotic
      molecule. Here, we found that the metastatic MDA-MB-231 breast cancer cells
      expressed much higher levels of hPEBP4 than the nonmetastatic MCF-7 breast cancer
      cells and that the expression levels of hPEBP4 were positively correlated with
      the metastasis of clinical breast cancer. The hPEBP4 overexpression in the MDA-MB
      231 cells significantly promoted cell invasion in vitro and increased the
      development of lymph node metastasis in vivo. Conversely, the silencing of hPEBP4
      suppressed the cell-invasive ability both in vitro and in vivo. Further
      investigation showed that hPEBP4 promoted the expression or activity of the
      metastasis-related proteinases MMP (matrix metalloproteinase) 2, MMP9 and MMP13.
      This hPEBP4-potentiated cell invasion and MMP expression is due to an increase in
      Akt activation. Knockdown of Akt restored hPEBP4-induced breast tumor metastasis
      in the hPEBP4-MDA-MB-231 xenograft mouse model. Moreover, we found that hPEBP4
      functioned as a scaffolding molecule and enhanced the association of Akt with Src
      to promote Akt tyrosine phosphorylation, a prerequisite for the full activation
      of Akt, in a phosphatidylethanolamine-binding domain-dependent manner. Given the
      present information about human breast cancer, these functional data from cell
      culture and animal studies suggest that, in human breast cancer hPEBP4 is a novel
      and clinically relevant metastasis accelerator gene and may be a new diagnostic
      marker and therapeutic target for breast cancer metastasis. 

PMID- 24276247
TI  - Enhanced expression of transferrin receptor 1 contributes to oncogenic signalling
      by sphingosine kinase 1.
AB  - Sphingosine kinase 1 (SK1) is a lipid kinase that catalyses the formation of
      sphingosine-1-phosphate (S1P). Considerable evidence has implicated elevated
      cellular SK1 in tumour development, progression and disease severity. In
      particular, SK1 has been shown to enhance cell survival and proliferation and
      induce neoplastic transformation. Although S1P has been found to have both cell
      surface G-protein-coupled receptors and intracellular targets, the specific
      downstream pathways mediating oncogenic signalling by SK1 remain poorly defined.
      Here, using a gene expression array approach, we have demonstrated a novel
      mechanism whereby SK1 regulates cell survival, proliferation and neoplastic
      transformation through enhancing expression of transferrin receptor 1 (TFR1). We
      showed that elevated levels of SK1 enhanced total as well as cell-surface TFR1
      expression, resulting in increased transferrin uptake into cells. Notably, we
      also found that SK1 activation and localization to the plasma membrane, which are
      critical for its oncogenic effects, are necessary for regulation of TFR1
      expression specifically through engagement of the S1P G-protein coupled receptor,
      S1P2. Furthermore, we showed that blocking TFR1 function with a neutralizing
      antibody inhibits SK1-induced cell proliferation, survival and neoplastic
      transformation of NIH3T3 fibroblasts. Similar effects were observed following
      antagonism of S1P2. Together these findings suggest that TFR1 has an important
      role in SK1-mediated oncogenesis. 

PMID- 24276248
TI  - Metastatic castration-resistant prostate cancer: new therapies, novel combination
      strategies and implications for immunotherapy.
AB  - For the past decade, docetaxel has remained the global standard of care for
      frontline treatment of metastatic castration-resistant prostate cancer (mCRPC).
      Until recently, there were limited options for patients with mCRPC following
      docetaxel failure or resistance, but now the approved treatment choices for these
      patients have expanded to include abiraterone acetate, cabazitaxel and
      enzalutamide. Additionally, the radioactive therapeutic agent radium-223
      dichloride has been recently approved in patients with CRPC with bone metastases.
      Although each of these agents has been shown to convey significant survival
      benefit as a monotherapy, preclinical findings suggest that combining such
      innovative strategies with traditional treatments may achieve additive or
      synergistic effects, further augmenting patient benefit. This review will discuss
      the transformation of the post-docetaxel space in mCRPC, highlighting the
      spectrum of newly approved agents in this setting in the USA and the European
      Union, as well as summarizing treatments with non-chemotherapeutic mechanisms of
      action that have demonstrated promising results in recent phase 3 trials. Lastly,
      this review will address the potential of combinatorial regimens in mCRPC,
      including the pairing of novel immunotherapeutic approaches with chemotherapy,
      radiotherapy or androgen ablation. 

PMID- 24276249
TI  - An evidence-based warfarin management protocol reduces surgical delay in hip
      fracture patients.
AB  - BACKGROUND: Up to 4% of patients presenting with a hip fracture may be on
      warfarin at admission. There is little consensus on the timing, dosage or route
      of vitamin K administration. We aimed to evaluate the impact of a locally
      developed, evidence-based protocol for perioperative warfarin management on the
      admission-to-operation time (AOT) in hip fracture patients. MATERIALS AND
      METHODS: Clinical and demographic data were collected prospectively for hip
      fracture patients who were on warfarin at the time of admission (post-protocol
      group) and compared to a historical control group of patients who were on
      warfarin before implementation of the protocol (pre-protocol group). Univariate
      analysis was undertaken to identify any significant differences between the two
      groups. RESULTS: Twenty-seven patients in the pre-protocol group (27/616, 4.4%)
      and 40 patients in the post-protocol group (4.7%, 40/855) were on warfarin at
      admission. There was a significant reduction in the median AOT from 73 h (IQR 46
      105) to 37.7 h (IQR 28-45) after implementation of the warfarin protocol (p <
      0.001). The proportion of patients operated on within 48 h of admission increased
      from 30% (8/27) in the pre-protocol group to 80% (32/40) in the post-protocol
      group (p < 0.001). No significant differences in hospital length of stay (p =
      0.77) or the postoperative warfarin recommencement time (p = 0.90) were noted
      between the two groups. CONCLUSION: Implementation of a perioperative warfarin
      management protocol can expedite surgery in hip fracture patients, but did not
      reduce hospital stay in our cohort, possibly because of a delay in recommencing
      warfarin in these patients postoperatively. LEVEL OF EVIDENCE: Level III.

PMID- 24276250
TI  - A biomechanical comparison between locked 3.5-mm plates and 4.5-mm plates for the
      treatment of simple bicondylar tibial plateau fractures: is bigger necessarily
      better?
AB  - BACKGROUND: Evolution of periarticular implant technology has led to stiffer,
      more stable fixation constructs. However, as plate options increase, comparisons
      between different sized constructs have not been performed. The purpose of this
      study is to biomechanically assess any significant differences between 3.5- and
      4.5-mm locked tibial plateau plates in a simple bicondylar fracture model.
      MATERIALS AND METHODS: A total of 24 synthetic composite bone models (12
      Schatzker V and 12 Schatzker VI) specimens were tested. In each group, six
      specimens were fixed with a 3.5-mm locked proximal tibia plate and six specimens
      were fixed with a 4.5-mm locking plate. Testing measures included axial ramp
      loading to 500 N, cyclic loading to 10,000 cycles and axial load to failure.
      RESULTS: In the Schatzker V comparison model, there were no significant
      differences in inferior displacement or plastic deformation after 10, 100, 1,000
      and 10,000 cycles. In regards to axial load, the 4.5-mm plate exhibited a
      significantly higher load to failure (P = 0.05). In the Schatzker VI comparison
      model, there were significant differences in inferior displacement or elastic
      deformation after 10, 100, 1,000, and 10,000 cycles. In regards to axial load,
      the 4.5-mm plate again exhibited a higher load to failure, but this was not
      statistically significant (P = 0.21). CONCLUSIONS: In the advent of technological
      advancement, periarticular locking plate technology has offered an invaluable
      option in treating bicondylar tibial plateau fractures. Comparing the
      biomechanical properties of 3.5- and 4.5-mm locking plates yielded no significant
      differences in cyclic loading, even in regards to elastic and plastic
      deformation. Not surprisingly, the 4.5-mm plate was more robust in axial load to
      failure, but only in the Schatzker V model. In our testing construct, overall,
      without significant differences, the smaller, lower-profile 3.5-mm plate seems to
      be a biomechanically sound option in the reconstruction of bicondylar plateau
      fractures.

PMID- 24276251
TI  - One-step RT-droplet digital PCR: a breakthrough in the quantification of
      waterborne RNA viruses.
AB  - Water contamination by viruses has an increasing worldwide impact on human
      health, and has led to requirements for accurate and quantitative molecular
      tools. Here, we report the first one-step reverse-transcription droplet digital
      PCR-based absolute quantification of a RNA virus (rotavirus) in different types
      of surface water samples. This quantification method proved to be more precise
      and more tolerant to inhibitory substances than the benchmarking reverse
      transcription real-time PCR (RT-qPCR), and needs no standard curve. This new tool
      is fully amenable for the quantification of viruses in the particularly low
      concentrations usually found in water samples. 

PMID- 24276252
TI  - NO(2) measurement artifacts in the presence of soot.
AB  - Nitrogen dioxide is a regulated pollutant, which is measured routinely. Since it
      can be formed during combustion processes, it is often measured in the presence
      of soot. This study investigates the possible artifact formation due to the
      interaction of soot and NO2 in the sampling lines and instrument prefilters. The
      transfer of varying NO2 concentrations through filters and tubes coated with
      different kinds of soot was investigated by using a dedicated photoacoustic soot
      and NO2 analyzer (TwinPAS). The effects of flow rate, temperature, relative
      humidity, tubing respectively filter material, soot reactivity, and passivation
      on the NO2 measurement artifacts have been investigated. We found significant
      lags (up to 2 min) of the NO2 transfer as well as total NO2 losses of up 10 %.

PMID- 24276253
TI  - Simulation of oxidative stress of guanosine and 8-oxo-7,8-dihydroguanosine by
      electrochemically assisted injection-capillary electrophoresis-mass spectrometry.
AB  - Oxidative stress plays a crucial role in DNA and RNA damage within biological
      cells. As a consequence, mutations of DNA can occur, leading to disorders like
      cancer and neurodegenerative and cardiovascular diseases. The oxidative attack of
      guanosine and 8-oxo-7,8-dihydroguanosine is simulated by electrochemistry coupled
      to capillary electrophoresis-mass spectrometry. The electrochemical conversion of
      the compound of interest is implemented in the injection protocol termed
      electrochemically assisted injection (EAI). In this way, oxidation products of
      guanosine can be generated electrochemically, separated by capillary
      electrophoresis, and detected by electrospray ionization time-of-flight mass
      spectrometry (EAI-CE-MS). A fully automated laboratory-made EAI cell with an
      integrated buffer reservoir and a compartment holding screen-printed electrodes
      is used for the injection. In this study, parameters like pH of the sample
      solution and the redox potential applied during the injection were investigated
      in terms of corresponding formation of well-known markers of DNA damage. The
      important product species, 8-oxo-7,8-dihydroguanosine, was investigated in a
      separate study to distinguish between primary and secondary oxidation products. A
      comparison of product species formed under alkaline, neutral, and acidic
      conditions is presented. To compare real biological systems with an analytical
      approach for simulation of oxidative stress, it is desirable to have a well
      defined control over the redox potential and to use solutions, which are close to
      physiological conditions. In contrast to typical HPLC-MS protocols, the
      hyphenation of EAI, CE, and MS enables the generation and separation of species
      involved without the use of organic solvents. Thus, information of the
      electrochemical behavior of the nucleoside guanosine as well as the primary
      oxidation product 8-oxo-7,8-dihydroguanosine can be characterized under
      conditions close to the physiological situation. In addition, the migration
      behavior found in CE separations of product species can be used to identify
      compounds if several possible species have the same mass-to-charge values
      determined by MS detection. 

PMID- 24276254
TI  - [Intrascrotal lipoblastoma in childhood: diagnostic strategies and therapy
      planning].
AB  - Based on a case report of an intrascrotal lipoblastoma in childhood, we present
      the preoperative diagnostic algorithm and the main differential diagnoses in
      testicular and paratesticular tumors as well as their surgical management. An 8
      week-old infant was admitted with a scrotal tumor known since birth. MRI showed a
      pinnate vessel supply, originating in the left internal iliac artery. The tumor
      was exposed operatively and could be completely removed. Intrascrotal
      lipoblastoma are rare. Like most testicular and paratesticular tumors in
      childhood lipoblastomas are benign. Today ultrasound and Doppler sonography are
      basic tools for diagnosis and surgical planning in testicular and scrotal tumors
      in childhood. In some cases MRI can provide additional important information for
      surgical planning. In contrast to adults testis sparing surgery is favoured in
      children. 

PMID- 24276255
TI  - Finding a new generation of spies and manuscript reviewers.
AB  - This material was presented as a poster at the Seventh International Congress on
      Peer Review and Biomedical Publication, 8-10 September 2013, Chicago, IL, USA. 

PMID- 24276256
TI  - Calcium channel blockers as tocolytics: principles of their actions, adverse
      effects and therapeutic combinations.
AB  - Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment
      of premature labour. Their mechanism of action in tocolysis involves the blockade
      of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta
      adrenergic receptors (beta-ARs) and sexual hormones. In clinical practice, most
      experience has been gained with the use of nifedipine, whose efficacy is superior
      or comparable to those of beta-agonists and oxytocin antagonists. Additionally,
      it has a favourable adverse effect profile as compared with the majority of other
      tocolytics. The most frequent and well-tolerated side-effects of CCBs are
      tachycardia, headache and hypotension. In tocolytic therapy efforts are currently
      being made to find combinations of tocolytic agents that yield better therapeutic
      action. The available human and animal studies suggest that the combination of
      CCBs with beta-AR agonists is beneficial, although such combinations can pose
      risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular
      diseases. Preclinical data indicate the potential benefit of combinations of CCBs
      and oxytocin antagonists. However, the combinations of CCBs with progesterone or
      cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to
      remain one of the most important groups of drugs for the rapid inhibition of
      premature uterine contractions. Their significance may be magnified by further
      clinical studies on their combined use for tocolysis. 

PMID- 24276257
TI  - Virtual lead identification of farnesyltransferase inhibitors based on ligand and
      structure-based pharmacophore techniques.
AB  - Farnesyltransferase enzyme (FTase) is considered an essential enzyme in the Ras
      signaling pathway associated with cancer. Thus, designing inhibitors for this
      enzyme might lead to the discovery of compounds with effective anticancer
      activity. In an attempt to obtain effective FTase inhibitors, pharmacophore
      hypotheses were generated using structure-based and ligand-based approaches built
      in Discovery Studio v3.1. Knowing the presence of the zinc feature is essential
      for inhibitor's binding to the active site of FTase enzyme; further customization
      was applied to include this feature in the generated pharmacophore hypotheses.
      These pharmacophore hypotheses were thoroughly validated using various procedures
      such as ROC analysis and ligand pharmacophore mapping. The validated
      pharmacophore hypotheses were used to screen 3D databases to identify possible
      hits. Those which were both high ranked and showed sufficient ability to bind the
      zinc feature in active site, were further refined by applying drug-like criteria
      such as Lipiniski's "rule of five" and ADMET filters. Finally, the two candidate
      compounds (ZINC39323901 and ZINC01034774) were allowed to dock using CDOCKER and
      GOLD in the active site of FTase enzyme to optimize hit selection. 

PMID- 24276258
TI  - Dysregulation of the Mammalian Target of Rapamycin and p27Kip1 Promotes Intimal
      Hyperplasia in Diabetes Mellitus.
AB  - The proliferation and migration of vascular smooth muscle cells (VSMCs) in the
      intima of an artery, known as intimal hyperplasia, is an important component of
      cardiovascular diseases. This is seen most clearly in the case of in-stent
      restenosis, where drug eluting stents are used to deliver agents that prevent
      VSMC proliferation and migration. One class of agents that are highly effective
      in the prevention of in-stent restenosis is the mammalian Target of Rapamycin
      (mTOR) inhibitors. Inhibition of mTOR blocks protein synthesis, cell cycle
      progression, and cell migration. Key to the effects on cell cycle progression and
      cell migration is the inhibition of mTOR-mediated degradation of p27Kip1 protein.
      p27Kip1 is a cyclin dependent kinase inhibitor that is elevated in quiescent
      VSMCs and inhibits the G1 to S phase transition and cell migration. Under normal
      conditions, vascular injury promotes degradation of p27Kip1 protein in an mTOR
      dependent manner. Recent reports from our lab suggest that in the presence of
      diabetes mellitus, elevation of extracellular signal response kinase activity may
      promote decreased p27Kip1 mRNA and produce a relative resistance to mTOR
      inhibition. Here we review these findings and their relevance to designing
      treatments for cardiovascular disease in the presence of diabetes mellitus. 

PMID- 24276259
TI  - Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs.
AB  - Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for
      the protection of multicellular organisms such as plants and animals from
      infection. The number of AMPs discovered per year increased steadily since the
      1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and
      animals have been registered into the antimicrobial peptide database (APD). The
      majority of these AMPs (>86%) possess 11-50 amino acids with a net charge from 0
      to +7 and hydrophobic percentages between 31-70%. This article summarizes peptide
      discovery on the basis of the APD. The major methods are the linguistic model,
      database screening, de novo design, and template-based design. Using these
      methods, we identified various potent peptides against human immunodeficiency
      virus type 1 (HIV-1) or methicillin-resistant Staphylococcus aureus (MRSA). While
      the stepwise designed anti-HIV peptide is disulfide-linked and rich in arginines,
      the ab initio designed anti-MRSA peptide is linear and rich in leucines. Thus,
      there are different requirements for antiviral and antibacterial peptides, which
      could kill pathogens via different molecular targets. The biased amino acid
      composition in the database-designed peptides, or natural peptides such as theta
      defensins, requires the use of the improved two-dimensional NMR method for
      structural determination to avoid the publication of misleading structure and
      dynamics. In the case of human cathelicidin LL-37, structural determination
      requires 3D NMR techniques. The high-quality structure of LL-37 provides a solid
      basis for understanding its interactions with membranes of bacteria and other
      pathogens. In conclusion, the APD database is a comprehensive platform for
      storing, classifying, searching, predicting, and designing potent peptides
      against pathogenic bacteria, viruses, fungi, parasites, and cancer cells. 

PMID- 24276261
TI  - Phorbol ester modulation of Ca2+ channels mediates nociceptive transmission in
      dorsal horn neurones.
AB  - Phorbol esters are analogues of diacylglycerol which activate C1 domain proteins,
      such as protein kinase C (PKC). Phorbol ester/PKC pathways have been proposed as
      potential therapeutic targets for chronic pain states, potentially by
      phosphorylating proteins involved in nociception, such as voltage-dependent Ca2+
      channels (VDCCs). In this brief report, we investigate the potential involvement
      of CaV2 VDCC subtypes in functional effects of the phorbol ester, phorbol 12
      myristate 13-acetate (PMA) on nociceptive transmission in the spinal cord.
      Effects of PMA and of selective pharmacological blockers of CaV2 VDCC subtypes on
      nociceptive transmission at laminae II dorsal horn neurones were examined in
      mouse spinal cord slices. Experiments were extended to CaV2.3(-/-) mice to
      complement pharmacological studies. PMA increased the mean frequency of
      spontaneous postsynaptic currents (sPSCs) in dorsal horn neurones, without an
      effect on event amplitude or half-width. sPSC frequency was reduced by selective
      VDCC blockers, w-agatoxin-IVA (AgTX; CaV2.1), w-conotoxin-GVIA (CTX; CaV2.2) or
      SNX-482 (CaV2.3). PMA effects were attenuated in the presence of each VDCC
      blocker and, also, in CaV2.3(-/-) mice. These initial data demonstrate that PMA
      increases nociceptive transmission at dorsal horn neurones via actions on
      different CaV2 subtypes suggesting potential anti-nociceptive targets in this
      system. 

PMID- 24276260
TI  - How "Pharmacoresistant" is Cav2.3, the Major Component of Voltage-Gated R-type
      Ca2+ Channels?
AB  - Membrane-bound voltage-gated Ca2+ channels (VGCCs) are targets for specific
      signaling complexes, which regulate important processes like gene expression,
      neurotransmitter release and neuronal excitability. It is becoming increasingly
      evident that the so called "resistant" (R-type) VGCC Cav2.3 is critical in
      several physiologic and pathophysiologic processes in the central nervous system,
      vascular system and in endocrine systems. However its eponymous attribute of
      pharmacologic inertness initially made in depth investigation of the channel
      difficult. Although the identification of SNX-482 as a fairly specific inhibitor
      of Cav2.3 in the nanomolar range has enabled insights into the channels
      properties, availability of other pharmacologic modulators of Cav2.3 with
      different chemical, physical and biological properties are of great importance
      for future investigations. Therefore the literature was screened systematically
      for molecules that modulate Cav2.3 VGCCs. 

PMID- 24276264
TI  - Fine structure, distribution and frequency of plasmodesmata and pits in the
      cortex ofLaminaria hyperborea andL. saccharina.
AB  - Prior to a long-distance transport of photoassimilate in the sieve elements
      ofLaminaria, a parenchyma transport across the cortex must occur. It is suggested
      that this transport is a symplastic one. The structural basis for this statement,
      continuous cytoplasmic interconnections of cells along the transport pathway, is
      demonstrated here forL. hyperborea andL. saccharina. The distribution, size, and
      frequency of pit fields in cell walls of all planes were determined. The data
      suggest that the conductivity for assimilate transport in the cortex is highest
      in the long axis of the thallus, not radially across the cortex. The fine
      structure, arrangement and number of plasmodesmata in pit fields were studied.
      The estimated flux rates and the anatomical findings clearly point to a
      symplastic parechyma transport of photoassimilate in the cortex ofLaminaria. 

PMID- 24276262
TI  - Trends in otitis media-related health care use in the United States, 2001-2011.
AB  - IMPORTANCE: Otitis media (OM) is a leading cause of pediatric health care visits
      and the most frequent reason children consume antibiotics or undergo surgery.
      During recent years, several interventions have been introduced aiming to
      decrease OM burden. OBJECTIVE: To study the trend in OM-related health care use
      in the United States during the pneumococcal conjugate vaccine (PCV) era (2001
      2011). DESIGN, SETTING, AND PARTICIPANTS: An analysis of an insurance claims
      database of a large, nationwide managed health care plan was conducted. Enrolled
      children aged 6 years or younger with OM visits were identified. MAIN OUTCOMES
      AND MEASURES: Annual OM visit rates, OM-related complications, and surgical
      interventions were analyzed. RESULTS: Overall, 7.82 million unique children (5.51
      million child-years) contributed 6.21 million primary OM visits; 52% were boys
      and 48% were younger than 2 years. There was a downward trend in OM visit rates
      from 2004 to 2011, with a significant drop that coincided with the advent of the
      13-valent vaccine (PCV-13) in 2010. The observed OM visit rates in 2010
      (1.00/child-year) and 2011 (0.81/child-year) were lower than the projected rates
      based on the 2005-2009 trend had there been no intervention (P < .001). Recurrent
      OM (>=3 OM visits within 6-month look-back) rates decreased at 0.003/child-year
      (95% CI, 0.002-0.004/child-year) in 2001-2009 and at 0.018/child-year (95% CI,
      0.008-0.028/child-year) in 2010-2011. In the PCV-13 premarket years, there was a
      stable rate ratio (RR) between OM visit rates in children younger than 2 years
      and in those aged 2 to 6 years (RR, 1.38; 95% CI, 1.38-1.39); the RR decreased
      significantly (P < .001) during the transition year 2010 (RR 1.32; 95% CI, 1.31
      1.33) and the postmarket year 2011 (RR 1.01; 95% CI, 1.00-1.02). Tympanic
      membrane perforation/otorrhea rates gradually increased (from 3721 per 100,000 OM
      child-years in 2001 to 4542 per 100,000 OM child-years in 2011; P < .001); the
      increase was significant only in the older children group. Mastoiditis rates
      substantially decreased (from 61 per 100,000 child-years in 2008 to 37 per
      100,000 child-years in 2011; P < .001). Ventilating tube insertion rate decreased
      by 19% from 2010 to 2011 (P = .03). CONCLUSIONS AND RELEVANCE: There was an
      overall downward trend in OM-related health care use from 2001 to 2011. The
      significant reduction in OM visit rates in 2010-2011 in children younger than 2
      years coincided with the advent of PCV-13. Although tympanic membrane
      perforation/otorrhea rates steadily increased during that period, mastoiditis and
      ventilating tube insertion rates decreased in the last years of the study.

PMID- 24276265
TI  - Vanadium an essential element for some marine macroalgae.
AB  - In some marine algae cultivated axenically in the artificial medium ASP6 F2 (pH
      8.3) vanadium at 1-100 MUg l(-1) increases the fresh weight. In the multicellular
      brown algaFucus spiralis 10 MUg V I(-1) enhances the fresh weight by about 400%
      while in the green algaEnteromorpha compressa the yield is increased by 90%. Red
      algae do not respond to vanadium. InFucus morphological effects are displayed in
      more frequent branching and/or broader blades. No significant increase in the
      chlorophyll content could be demonstrated at the early stage at which these
      morphological effects first appeared. Later the chlorophyll content increased. 

PMID- 24276266
TI  - Changes in the content of modified nucleotides of total transfer RNA of wheat
      seedlings during greening.
AB  - The contents in minor nucleotides of total transfer RNA (tRNA) of etiolated and
      light-grown wheat (Triticum aestivum L.) seedlings and of seedlings illuminated
      for 24 or 48 h were examined. The total tRNA of seedlings illuminated 24 h
      contained more, and that from seedlings illuminated 48 h still more modified
      nucleotides than that from etiolated ones. Thus, the appearance of the
      characteristic minor nucleotides of tRNA of light-grown wheat seedlings needs a
      rather long greening period, of at least 48 h. 

PMID- 24276267
TI  - Extraction and immunochemical assays of a tubulin-like factor in cotton
      seedlings.
AB  - Antibodies to tubulin were prepared in rabbits by immunization with reduced
      carboxymethylated calf-brain tubulin. In immunodiffusion tests the antibodies
      showed full cross reactivity with the immunogen as well as with native calf-brain
      tubulin. The same antibodies showed cross reactivity with a factor in extract of
      cotton (Gossypium hirsutum L.) cotyledons but there was no full immunological
      identity between calf-brain tubulin and this factor. A solid-phase
      radioimmunoassay for quantitative estimation of this plant tubulin-like factor
      was developed. It measured the binding of antibodies to immobilized calf-native
      tubulin. Competition between the unknown soluble tubulin-like factor, and
      immobilized tubulin was assayed at serum dilution of 1:50. Extraction conditions
      which preserved the antigenic properties of the tubulin-like factor from cotton
      cotyledons were defined. The radioimmunoassay measured quantities of the tubulin
      like factor in the range of 0.1-10 MUg-equivalents of calf-brain tubulin.
      Immediately after homogenization of the tissue only 25% of the total amount of
      tubulin-like activity was present in soluble form, while most of it remained in
      the insoluble fraction. Apparent maximal solubilization was achieved
      spontaneously 10 h after homogenization or by treatment with guanidine
      hydrochloride. These results indicate that in this material, tubulin is not
      released immediately by homogenization but remains assembled in microtubules and
      or in a bound or sequestered form. 

PMID- 24276268
TI  - Increased drought tolerance of mycorrhizal onion plants caused by improved
      phosphorus nutrition.
AB  - Onion plants (Allium cepa L, cv. Downing Yellow Globe) grown in pots and infected
      by the mycorrhizal fungusGlomus etunicatus Becker and Gerdemann were more drought
      tolerant than were non-mycorrhizal individials when exposed to several periods of
      soil water stress separated by periods of high water supply, as shown by greater
      fresh and dry weights and higher tissue phosphorus levels in the mycorrhizal
      plants. The tissues of stressed, non-mycorrhizal plants were deficient in P,
      despite the fact that only non-mycorrhizal plants were fertilized with high
      levels of P (26 mg P per 440 g soil). Differences in plant water relations (leaf
      water potentials or transpiration rates) and changes in soil P levels which may
      have affected plant growth were investigated, and discounted as factors important
      for the results. The P nutrition of plants has been implicated in the ability of
      plants to tolerate drought and it was concluded that the ability of the
      mycorrhizal fungus to maintain adequate P nutrition in the onions during soil
      water stress was a major factor in the improved drought tolerance. Infection of
      the root by the fungus was found not to be affected by water stress or P
      fertilization but fungal reproduction, as determined by spore numbers in the
      soil, was decreased by water stress and by P fertilization. 

PMID- 24276269
TI  - Ultrastructure of the sporophyte foot-gametophyte vaginula complex inTimmiella
      barbuloides (Brid.) Moenk.
AB  - The sporophyte foot of the mossTimmiella barbuloides consists of an unistratose
      epidermis of transfer cells, a parenchymatous cortex, and a small central strand
      consisting only of hydroids. The parenchymatous tissue of the vaginula develops
      one layer of transfer cells opposite the foot, whose lower extremity extends into
      the gametophyte stem's central strand. From the bottom to the top of the foot the
      ultrastructure of the sporophyte transfer cells shows some gradual changes that
      appear related to a functional specialization of these cells. According to a
      centripetal gradient, the quantity of plastid starch progressively lessens in
      both vaginula parenchyma and foot cortex. the observed morphological patterns
      suggest that in the foot-vaginula complex nutrients are translocated radially up
      to the sporophyte central strand. 

PMID- 24276270
TI  - Temporal and spatial changes of cellulose synthesis inClosterium acerosum
      (Schrank) Ehrenberg during cell growth.
AB  - The amount and distribution of wall microfibril synthesis were investigated in
      the cell-division cycle ofClosterium acerosum. Electron-microscopic examination
      and a methylation analysis of alkali-extracted wall fragments showed that alkali
      extracted wall was mainly composed of microfibrils and that the microfibrils ofC.
      acerosum were 4-linked glucans, i.e., cellulose. Cellulose synthesis was measured
      as incorporation of(14)C, fed to cells as NaHCO3, into extracted wall fragments.
      Extensive cellulose synthesis was coincident with septum formation, continued for
      more than 6 h and then ceased. It was found by microautoradiography that
      cellulose synthesis after cell division was essentially restricted to the
      expanding new semicells. Such a restricted distribution of cellulose synthesis
      was maintained for more than 6 h after septum formation, i.e., for more than 2 h
      after the cessation of expansion; afterwards, cellulose synthesis in some, but
      not all, cells became extended to the old semicells, and then ceased.
      Considerable cellulose synthesis also took place in the band-like expanding part
      of non-divided cells, indicating that cell division was not necessarily required
      for the induction of cellulose synthesis and the latter was coupled with cell
      expansion. Extension of cellulose synthesis to old semicells was brought about in
      divided cells by treatment with 3 mM colchicine, 28 MUM vinblastine, 50 MUM
      isopropyl-N-phenylcarbamate or 1 MUM isopropyl-N(3-chlorophenyl)carbamate,
      indicating that microtubules are involved in the limitation of cellulose
      synthesis to the new semicells. 

PMID- 24276271
TI  - Protein turnover in the attached leaves of non-stressed and stressed barley
      seedlings.
AB  - Protein turnover was examined, using tritiated water, in various 2-cm regions of
      7-11-d-old, first leaves of barley (Hordeum vulgare). Differences were found
      between the regions in their protein turnover and their responses to stress. The
      rate constant for degradation for total protein was the same throughout the leaf
      and the average half-life (t1/2) of protein=approx. 220 h. Only in the older
      regions did a 24-h pulse of(3)H2O preferentially label protein with a t1/2 (90 h)
      considerably shorter than the t1/2 for total protein. 'Soluble' protein was
      degraded faster than 'insoluble' protein and contained an appreciable short-lived
      protein component observable by short-pulse labelling. The rate of protein
      synthesis was greatest in the cells of the youngest region and declined as each
      region aged. The mean rate of protein synthesis over the 4-d period was 4 and 7
      nmol h(-1) of amino-N with respect to the regions 1-3 and 7-9 cm from the leaf
      tip. Seedlings, stressed by adding polyethylene glycol (2.0 MPa) to the roots,
      showed a marked loss of protein from the older leaf regions with only small
      losses in the younger regions. Amino acids accumulated in the younger region
      continuously whereas in the older region little accumulation occurred until day 3
      of stress when proline levels increased. Protein synthesis was decreased by
      between 30% and 50% in all leaf regions. In the region 1-3 cm from the leaf tip,
      the rate of protein degradation of total protein was enhanced and equalled the
      rate of degradation of 24-h-pulse-labelled protein which was not itself
      significantly affected by stress (t1/2=approx. 90 h). In the region 3-5 cm, the
      degradation of both 4-d and 24-h-labelled protein was enhanced by stress to rates
      similar to those found in the region 1-3 cm. This was largely through increases
      in the degradation of the 'insoluble' protein, but the degradation of 'soluble'
      protein was also raised. Protein degradation in the region 7-9 cm was not
      affected by stress. 

PMID- 24276272
TI  - Effects of abscisic acid, cytokinins, and light on isoflavonoid phytoalexin
      accumulation inPhaseolus vulgaris L.
AB  - Cotyledons ofPhaseolus vulgaris L. contain small amounts of phaseollin and
      kievitone. Isolating the cotyledons from the plant does not alter phaseollin
      levels. Kievitone levels, however, although not affected in light-incubated
      cotyledons, increased rapidly in dark-incubated cotyledons. Abscisic acid (ABA)
      at 10(-4) M stimulated the accumulation of phaseollin in excised cotyledons in
      both light and darkness, whereas benzylaminopurine (BAP) increased these levels
      only in the light. The kievitone level was influenced by ABA and BAP only in dark
      incubated cotyledons, i.e., inhibited at 10(-4) M. When excised cotyledons were
      treated with mercuric chloride, both phaseollin and kievitone accumulated rapidly
      in both light and darkness. The effect of ABA on these cotyledons was similar to
      that on non-treated cotyledons. The results demonstrate that the synthesis of the
      two phytoalexins is regulated by separate mechanisms and indicate that the
      phytoalexin composition is dependent on the physiological condition of the
      cotyledons. ABA and BAP may play a role in the resistance response of the plant. 

PMID- 24276273
TI  - Variation in nicotine content of tobacco callus cultures.
AB  - Plants ofNicotiana tabacum L. cv. Burley 21 which showed no difference in
      nicotine content were used to establish callus cultures. Cultures were initiated
      from different plants and from different leaves within each plant. The nicotine
      content of the calli was determined, and the results subjected to an analysis of
      variance. Differences between plants and differences within plants significantly
      affected the nicotine content of the cultures. The differences between plants
      were transmitted sexually and asexually, providing evidence that they are
      genetically determined. No such differences in nicotine content were found
      between the plants from which the cultures were established, indicating that
      nicotine production in vitro involves additional genes to those which are needed
      for nicotine production in the plant. The differences within plants were further
      investigated by establishing callus cultures from pith explants taken from
      different parts of the stem. Explants from apical pith tissue gave calli having
      far more nicotine and more roots than cultures derived from basal pith explants.
      This results may reflect the proximity of the apical pith explants to the site of
      auxin synthesis in the stem apex. Callus cultures derived from pith explants
      showed greater growth and nicotine production than those derived from leaf
      explants when the calli were induced on Murashige-Skoog medium containing alpha
      naphthalene acetic acid. This result is in conflict with the widely held belief
      that explants from different parts of the plant give cultures with similar yields
      of species-specific compounds. 

PMID- 24276274
TI  - Induction of de novo synthesis of phenylalanine ammonia-lyase by L-alpha-aminooxy
      beta-phenylpropionic acid in suspension cultures ofDaucus carota L.
AB  - Application of L-alpha-aminooxy-beta-phenylpropionic acid (L-AOPP), a potent and
      specific competitive inhibitor of L-phenylalanine ammonia-lyase (PAL), to an
      anthocyanin-producing cell suspension culture ofDaucus carota results in a
      dramatic increase in extractable PAL activity and an accumulation of
      phenylalanine (Noe et al., 1980, Planta149, 283-287). Using an
      immunoprecipitation technique, evidence was obtained that the increase in PAL
      activity the result of de-novo synthesis. The activity of the other enzymes of
      the general phenylpropanoid metabolism, e.g., trans-cinnamate 4-hydroxylase and
      hydroxycinnamate: CoA ligase, were not affected by L-AOPP. This result strongly
      supports the view that PAL is regulated independently. 

PMID- 24276275
TI  - The presence and synthesis of the NADPH-protochlorophyllide oxidoreductase in
      barley leaves with a high temperature-induced deficiency of plastid ribosomes.
AB  - High-temperature-induced deficiency of plastid ribosomes in barley plants
      (Hordeum vulgare L.) was used as a system for studying the role of the cytoplasm
      in the synthesis of the NADPH-protochlorophyllide oxidoreductase. The enzyme is
      present in 33 degrees  C-grown plants. The failure of high-temperature-grown
      plants to accumulate chlorophyll during illumination is not caused by the absence
      of the protochlorophyllide-reducing enzyme. The synthesis of the NADPH
      protochlorophyllide oxidoreductase was studied by feeding [(35)S]methionine to
      the seedling and by following the incorporation of the radioactively labeled
      amino acid into plastid proteins. The NADPH-protochlorophyllide oxidoreductase
      was labeled in high-temperature-grown barley plants to the same extent as in
      control plants grown at 25 degrees  C. It is concluded that the 36,000-Mr
      polypeptide of the NADPH-protochlorophyllide oxidoreductase is synthesized
      outside the plastid on cytoplasmic 80S ribosomes. 

PMID- 24276276
TI  - Synthesis and turnover of the light-harvesting chlorophylla/b-protein inLemna
      gibba grown with intermittent red light: possible translational control.
AB  - Lemna gibba L. G-3 plants grown heterotrophically in the dark with intermittent
      red light (2 min every 8 h) contain a substantial amount of translatable mRNA
      encoding the light-harvesting chlorophyll (Chl)a/b-protein. However, very little
      [(35)S]methionine is incorporated into the apoproteins during a 1-h labeling
      period in the dark in these plants compared to plants grown in continuous white
      light. The Chla/b-protein mRNA is found to be associated with functioning
      polysomes in plants grown in the dark with intermittent red illumination (R
      plants). The small amounts of the apoproteins which are synthesized by these
      plants are found in the membrane fraction; neither the mature apoproteins nor
      their precursor(s) can be detected immunologically in the soluble fraction. The
      protein does not accumulate in these plants. Pulse-chase experiments with the R
      plants demonstrate that the newly synthesized apoproteins have a half-life of
      about 10 h in the dark. This turnover is not sufficient to explain the observed
      20-fold difference in [(35)S]methionine incorporation into the apoprotein between
      white-light-grown and R plants. We therefore suggest that the synthesis of the
      Chla/b-apoproteins can be regulated by a light-dependent step at the level of
      translation, and that this regulation occurs after the initiation of translation.

PMID- 24276277
TI  - The development of NAD(P)H-dependent and ferredoxin-dependent glutamate synthase
      in greening barley and pea leaves.
AB  - The activity of NAD(P)H-dependent glutamate synthase (E.C. 1.4.1.14) has been
      demonstrated in extracts from etiolated shoots of pea (Pisum sativum L.) and
      barley (Hordeum vulgare L.). This activity does not significantly alter upon
      greening of the etiolated shoots, and is at a similar level in light-grown
      material. Ferredoxin-dependent glutamate synthase (E.C. 1.4.7.1) has low activity
      in etiolated shoots but increases rapidly on greening. In light grown leaves
      ferredoxin-dependent activity is 30-40-fold higher than NAD(P)H-dependent
      activity. It is not considered that the NAD(P)H-dependent glutamate synthase
      plays an important role in ammonia assimilation in the photosynthetic tissue of
      higher plants. 

PMID- 24276279
TI  - Gas chromatographic-mass spectroscopic identification of protaglandin F2alpha in
      floweringKalanchoe blossfeldiana v. Poelln.
AB  - After further purification of a previously prepared impure compound from
      floweringKalanchoe blossfeldiana v. Poelln., and subjecting it to gas
      chromatography-mass spectrometry it was identified as prostaglandin F2alpha. The
      amount was 1-2 ng g(-1) fresh weight. This result demonstrates the presence of a
      prostaglandin in a higher plant. 

PMID- 24276278
TI  - Aspartate aminotransferases ofPanicum miliaceum L. andPanicum antidotale retz. :
      Inactivation and reconstitution.
AB  - L-Aspartate: 2-oxoglutarate transaminase was isolated and partially purified from
      leaves ofPanicum miliaceum (C4, NAD-malic enzyme type) and ofPanicum antidotale
      (C4, NADP-malic enzyme type). In each preparation two isoenzymes with different
      kinetic properties could be characterized. The enzyme activity was irreversibly
      inhibited by 2-aminooxyacetic acid and by 2-amino-4-methoxy-3-butenoic acid. The
      first inhibitor reacted with pyridoxal 5-phosphate, and its inhibition could be
      reversed by the exchange of the modified coenzyme. The second inhibitor binds not
      only to the coenzyme pyridoxal 5-phosphate, but also to the apoprotein. The
      results of the dissociation and reconstitution experiments were in agreement with
      the kinetic data, showing that the mode of inactivation was different for 2
      aminooxyacetic acid and 2-amino-4-methoxy-3-butenoic acid. 

PMID- 24276280
TI  - Induction of apoptosis by VB1 in breast cancer cells: the role of reactive oxygen
      species and Bcl-2 family proteins.
AB  - We have previously reported that the EVn-50 mixture of vitexins (lignan
      compounds) containing the purified vitexin (neolignan) compound, 6-hydroxy-4(4
      hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde,
      termed VB1, exhibits potent anticancer activity through the induction of
      apoptosis in several types of cancer cells, including MDA-MB-231 cells. However,
      the exact molecular mechanisms by which VB1 induces apoptosis in MDA-MB-231 cells
      have not yet been fully elucidated. In this study, to our knowledge, we provide
      for the first time mechanistic evidence that VB1-induced apoptosis in the human
      breast cancer line, MDA-MB-231, is associated with the generation of reactive
      oxygen species (ROS), the activation of caspases and the modulation of the
      expression of myeloid leukemia cell differentiation protein 1 (Mcl-1), B cell
      lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins. The silencing of Mcl-1
      by RNA interference enhanced VB1-induced apoptosis. In addition, VB1 did not
      induce ROS generation or apoptosis in the immortalized non-cancerous breast cell
      line, MCF-10A. Our findings reveal a novel mechanism underlying VB1-induced
      apoptosis, and highlight VB1 as a promising candidate for the therapy of human
      breast cancer.

PMID- 24276281
TI  - CD44 is prognostic for overall survival in the NCI randomized trial on breast
      conservation with 25 year follow-up.
AB  - CD44 is a transmembrane glycoprotein involved in numerous cellular functions,
      including cell adhesion and extracellular matrix interactions. It is known to be
      functionally diverse, with alternative splice variants increasingly implicated as
      a marker for tumor-initiating stem cells associated with poor prognosis. Here, we
      evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue
      specimens from patients treated on the National Cancer Institute 79-C-0111
      randomized trial of breast conservation versus mastectomy between 1979 and 1987
      were collected, and immunohistochemistry was performed using the standard isoform
      of CD44. Specimens were correlated with patient characteristics and outcomes.
      Survival analysis was performed using the log rank test. Fifty-one patients had
      evaluable tumor sections and available long-term clinical follow up data at a
      median follow up of 25.7 years. Significant predictors of OS were tumor size
      (median OFS 25.4 years for <=2 cm vs. 7.5 years for >2 cm, p = 0.001), nodal
      status (median OS 17.2 years for node-negative patients vs. 6.7 years for node
      positive patients, p = 0.017), and CD44 expression (median OS 18.9 years for CD44
      positive patients vs. 8.6 years for CD44 negative patients, p = 0.049). There was
      a trend toward increased PFS for patients with CD44 positive tumors (median PFS
      17.9 vs. 4.3 years, p = 0.17), but this did not reach statistical significance.
      These findings illustrate the potential utility of CD44 as a prognostic marker
      for early stage breast cancer. Subgroup analysis in patients with lymph node
      involvement revealed CD44 positivity to be most strongly associated with
      increased survival, suggesting a potential role of CD44 in decision making for
      axillary management. As there is increasing interest in CD44 as a therapeutic
      target in ongoing clinical trials, the results of this study suggest additional
      investigation regarding the role CD44 in breast cancer is warranted. 

PMID- 24276282
TI  - Quantification of copper binding to amyloid precursor protein domain 2 and its
      Caenorhabditis elegans ortholog. Implications for biological function.
AB  - Aberrant regulation of transition metals and the resultant disregulation of
      neuronal reactive oxygen species (ROS) are considered significant in the etiology
      of Alzheimer's disease (AD). We determined the solution structure of the D2
      domain of APL-1 (APL1-D2), the Caenorhabditis elegans ortholog of the amyloid
      precursor protein domain 2 (APP-D2). The copper binding affinities of APL1-D2 and
      APP-D2 were estimated and the ability of their copper complexes to promote
      formation of ROS was tested. The two protein domains are isostructural,
      consisting of a three-stranded beta-sheet packed against a short alpha-helix in a
      betaalphabetabeta fold. A six-residue insert in APL1-D2, absent in APP-D2, forms
      an extended loop. The putative copper binding ligands in APP-D2 are not conserved
      in APL1-D2 and this delineates a clear difference between them. APL1-D2 and APP
      D2 bind one equivalent of Cu(I) weakly, with dissociation constants KD ~10(-8.6)
      M and ~10(-10) M, respectively, and up to two equivalents of Cu(II) with KD
      values in the range 10(-6) -10(-8) M. The relative abilities of APL1-D2, APP-D2
      and amyloid-beta (Abeta) copper complexes to generate H2O2 correspond to their
      copper binding affinities. Copper affinities for Abeta (KD ~ 10(-10) M for both
      Cu(I) and Cu(II)) and APP-D2 are in a range allowing redox cycling to occur,
      albeit less efficiently for APP-D2. However, APL1-D2 binds Cu(I) and Cu(II) too
      weakly to sustain catalysis which further suggests that it plays no significant
      role in copper handling in C. elegans. Overall, the data are consistent with a
      possible role in copper homeostasis for APP-D2, but not APL1-D2.

PMID- 24276283
TI  - Analogs of sex pheromone of processionary moth,Thaumetopoea pityocampa: Synthesis
      and biological activity.
AB  - The synthesis and biological activity of some analogs of (Z)-13-hexadecen-11-ynyl
      acetate1, the major component of the sex pheromone of the processionary
      mothThaumetopoea pityocampa is described. The analogs have been formally derived
      by structural modification of the enyne and acetate functions of the parent
      compound1. In field tests, trifluoroacetate ester16 and the analog,11, with
      fluorine substitution at the olefin site, decreased the pheromone action, whereas
      epoxy derivative,10, from epoxidation of the olefin moiety in1, and propionate
      ester15 gave synergistic activity. The formate14 had a variable effect according
      to the composition of the lure. Formal reduction of the enyne to give the
      acetylene2 was found to retain activity. Alcohols12 and13, resulting from
      hydrolysis of the enyne1 and acetylene2, respectively, inhibited the action of
      their parent compounds. 

PMID- 24276284
TI  - Rubber substrates and their influence on isomerization of conjugated dienes in
      pheromone dispensers.
AB  - Release rate and degree of isomerization of pheromones with conjugated double
      bonds were studied in dispensers prepared from several rubber substrates. The
      substrates compared were made of rubber, cured with elemental sulfur or
      accelerators based on organic sulfur compounds or organic peroxides.
      Isomerization of the double bonds occurs immediately after impregnation of the
      substrate, and the degree of isomerization increases during field use and/or
      storage. The propensity of the isomers to isomerize corresponds to their
      proportion in the equilibrium mixture. AnE,Z isomer is isomerized faster than
      theE,E isomer, and finally a near-equilibrium mixture of the four isomers is
      present. Minimal isomerization was found in non-sulfur-cured substrates which are
      the material of choice. 

PMID- 24276285
TI  - Sex pheromone of European corn borer. : Ostrinia nubilalis: Polymorphism in
      various laboratory and field strains.
AB  - Sex gland extracts ofOstrinia nubilalis females collected in the wild or
      laboratory-reared from Switzerland, Italy, and Hungary were analyzed. Individuals
      collected in the north of Switzerland contained (Z)- and (E)-11-tetradecenyl
      acetate at the approximate ratio of 97?3 (Z type), in accordance with field
      responses of males and previous findings. On the other hand, females from a
      laboratory culture derived from field collections made in the same area and
      reared for four to five generations contained theZ andE isomers at ratios of ca.
      3?97 and 35?65, respectively. In the south, one of the eight wild females
      analyzed was of theZ type and the rest intermediate, whereas males were
      predominantly trapped with blends of the two isomers containing 60 to 97E. In a
      laboratory culture reared for one to two generations from corn borers collected
      in Hungary, three of nine females were of the intermediate type and the restZ.
      Small amounts of (Z)-11-hexadecenyl acetate were detected in female glands of
      theE strain; however, no effect of this compound could be observed in the field. 

PMID- 24276286
TI  - Volatile components of scent material from cotton-top tamarin (Saguinus o.
      oedipus) : A chemical and behavioral study.
AB  - The first chemical analysis of the volatile components of scent material from the
      cotton-top tamarin,Saguinus o. oedipus is presented. In contrast to our previous
      findings in saddle-back tamarins (Saguinus fuscicollis), the chemical composition
      of the scent marks is quite variable. Analysis of secretion expressed manually
      from different areas of the scent pads of sedated animals shows individual and
      regional variability. Only three components (squalene, cholesterol, andp
      methoxybenzaldehyde) were found in all scent mark samples analyzed. However,
      suprapubic secretions obtained from one sedated female contained, in addition, 12
      butyrate esters as well as five acetate esters which were homologous to the
      butyrates. The butyrate esters have been previously identified in scent material
      fromSaguinus fuscicollis. The variability of the composition of the scent
      material is discussed in relation to the scent-marking behavior of the cotton-top
      tamarins. Behavioral studies tested the ability of the cotton-top tamarins to
      discriminate between scent marks from conspecifics and scent marks from saddle
      back tamarins. The group of 12 subjects discriminated between the scent marks
      from both species in choice tests during which they could freely contact the
      scent samples. However, when scent marks were presented under a screen, so that
      the subjects could smell but not contact the stimuli, no discrimination was
      shown. Four individuals displayed more interest in the screened scent stimuli
      than all other subjects. When these animals were tested in a second experiment
      for their ability to discriminate between material from the two species on the
      basis of only volatile cues, it became evident that they were able to do so.
      These results indicate that volatile cues alone enable the tamarins to recognize
      scent marks from conspecifics, but that additional cues perceived during contact
      with the scent are important for its full attractiveness and/or informational
      content. 

PMID- 24276287
TI  - Computation of response factors for quantitative analysis of monoterpenes by gas
      liquid chromatography.
AB  - Response factors for quantitative analysis by gas-liquid chromatography were
      computed for 10 monoterpenes usingp-cymene as an internal standard. The results
      show that there is no significant variation in our estimates due to sample
      concentration, and very low variation due to the compound. The most significant
      deviation fromRF c=1.0 occurred with myrcene. We conclude that the underlying
      assumptions of quantitative analysis are met usingp-cymene as an internal
      standard for most plant or animal monoterpenes, and for total monoterpene
      content. 

PMID- 24276288
TI  - Effects of dietary protein and lupine alkaloids on growth and survivorship
      ofSpodoptera eridania.
AB  - Toxic chemicals and nutrients are often positively correlated within and among
      plants. We studied how such correlations affect the suitability of plants as food
      for herbivores by assessing the growth and survivorship ofSpodoptera eridania
      (army worm) on artificial diets containing lupine alkaloids and casein. We found
      that (1) the effects of casein were determined by other dietary components:
      increased dietary casein led to increased larval growth only when the diet was
      also high in wheat germ. (2) Dietary alkaloids were effective at very low
      concentrations, reducing both growth and survivorship. The alkaloids lupanine and
      sparteine were not synergistic in their effects, and the interaction between
      alkaloids and casein was significant only in the low-wheat-germ diets. (3) The
      effects of casein and alkaloids were generally apparent only in the first instar,
      and the growth of fifth-instar larvae was unaffected by diet. (4) Using these
      artificial diet experiments, we can make simple predictions about the food
      quality of plants grown under various nutrient regimes. These predictions are
      consistant with recent ideas about optimal plant defenses. 

PMID- 24276289
TI  - Algal phagostimulants for marine herbivorous gastropods.
AB  - Methanol extracts of the green algaUlva pertusa contain four kinds of
      glycerolipids that are active as feeding-stimulants for marine herbivorous
      gastropods. These compounds are digalactosyldiacylglycerol (DGDG), 1,2
      diacylglycerly-4'-O-(N,N,N-trimethyl)-homoserine (DGTH), 1-monoacylglyceryl-4'-O
      (N,N,N-trimethyl)-homoserine (MGTH), and 6-sulfoquinovosyldiacylglycerol (SQDG).
      The various gastropods exhibit marked specificity, however, as young
      abaloneHaliotis discus respond to DGDG and DGTH at minute dosages of 20-30
      MUg/sample zone, but do not respond to 300 MUg of SQDG, which is a phagostimulant
      for two other kinds of gastropods,Turbo comutus andOmphalius pfeifferi. 

PMID- 24276290
TI  - Sex pheromone of purplestriped shootworm,Zeiraphera unfortunana powell.
AB  - The analyses of virgin female sex pheromone gland extracts and gland volatiles by
      GC, GC-EAD and GC-MS, followed by field trapping experiments, have identified (E)
      9-dodecenyl acetate (E9-12?Ac) as the primary sex pheromone component of the
      purplestriped shootworm,Zeiraphera unfortunana. Dosages of 1.0-10.0 MUg ofE9
      12?Ac impregnated in rubber septa provide an effective trap bait and can be used
      for monitoring purposes. 

PMID- 24276291
TI  - Fluorinated analogs of aldehyde components of boll weevil pheromone : Synthesis
      and biological activity.
AB  - Analogs of the two geometrical isomers of the dimethylcyclohexylidene
      acetaldehyde component of the pheromone of the boll weevilAnthonomus grandis were
      synthesized in which the alpha-vinylic proton or the aldehydic proton were
      replaced by fluorine. These isosteric substitutions substantially alter charge
      distribution and reactivity of the enal system, as documented by spectroscopic
      changes and changes in reactivity. The electrophysiological activity of the (E)-
      and (Z)-acyl fluorides is two orders of magnitude lower than that of the natural
      aldehyde. In contrast, the EAG response of female antennae to the (E)- and (Z)
      alpha-fluoro compounds show that the thresholds are quite similar to (and in one
      isomer lower than) those of the natural aldehyde isomers. 

PMID- 24276292
TI  - Chemically mediated habitat recognition in shore insects (Coleoptera: Carabidae;
      Hemiptera: Saldidae).
AB  - Adults of 14 species of Carabidae and mixed nymphs and adults of two species of
      Saldidae, collected in habitats associated with a saline lakeshore, sedge fen,
      vernal pond, stream mud flat, salt spring, mud and sand river bank, pebble river
      bank, and a marine sand beach, aggregated in choice chambers above volatiles
      (allelochemics) collected from their habitats. In other tests adults of some
      carabid species responded to volatiles from habitats other than their own, and to
      arbitrarily selected individual components and mixtures of components of saline
      lakeshore volatiles. These results suggest that shore insects recognize habitat
      allelochemics and aggregate in areas where these compounds are emitted by
      resident microflora. It is proposed that some habitat allelochemics are short
      range signals that indicate locations of microhabitats used by shore insects for
      behaviors such as feeding, mating, and resting; in contrast, long-range
      allelochemics allow these insects to select their habitats from a distance. This
      hypothesis provides a mechanism for explaining how different shore habitats are
      partitioned among different species of shore insects. 

PMID- 24276293
TI  - Fatigue during high-intensity endurance exercise: the interaction between
      metabolic factors and thermal stress.
AB  - The purpose of this study was to examine the effects of hot (37 degrees  C) and
      cool (10 degrees  C) environments on cycling time to exhaustion (TTE), pH,
      lactate, and core temperature (Tc). Eleven endurance-trained subjects completed 4
      TTE trials: Hot 80% VO2max (H80), Cool 80% (C80), Hot 100% (H100), and Cool 100%
      VO2max (C100). Esophageal temperature and blood was sampled before, every 5
      minutes, at exhaustion, and 3 minutes after exercise and analyzed for lactate,
      pH, and HCO3-. Multifactorial analysis of variance with repeated measures was
      used to determine differences between mean values (+/- SD). Time to exhaustion
      was shorter in H100 and C100 vs. H80 and C80 (5.64 +/- 1.49 minutes, 5.83 +/-
      1.03 minutes, 12.82 +/- 2.0 minutes, and 24.85 +/- 6.0 minutes, respectively) and
      shorter in H80 vs. C80 (p < 0.01). The pH at exhaustion was different among all
      conditions (7.17 +/- 0.06, 7.15 +/- 0.07, 7.21 +/- 0.04, and 7.24 +/- 0.06 units
      for H100, C100, H80, and C80, respectively, p = 0.02). The Tc at exhaustion was
      lower in H100 and C100 (37.93 +/- 0.67 and 37.62 +/- 0.58 degrees  C) vs. H80 and
      C80 (38.54 +/- 0.51 degrees  C and 38.53 +/- 0.38 degrees  C) (p < 0.01). In H80
      and C80, the higher Tc likely played a greater role in the termination of
      exercise, whereas, in H100 and C100, pH and metabolic changes may have been more
      important. Despite these differences, neither an upper limit for Tc nor a lower
      limit for pH was identified; thus, fatigue based entirely on peripheral factors
      was not supported, and a combination of peripheral and central processes must be
      considered. The practical implications of these findings are that aerobic
      exercise at or near VO2max may be impacted more by metabolic factors, whereas
      lower intensities (~80% VO2max) may be affected more by heat stress; these
      differences should be considered when training for events of this type.

PMID- 24276294
TI  - The nature and prevalence of injury during CrossFit training.
AB  - CrossFit is a constantly varied, high intensity, functional movement strength and
      conditioning program which has seen a huge growth in popularity around the world
      since its inception twelve years ago. There has been much criticism as to the
      potential injuries associated with CrossFit training including rhabdomyolysis and
      musculoskeletal injuries. However to date no evidence exists in the literature to
      the injures and rates sustained. The purpose of this study was to determine the
      injury rates and profiles of CrossFit athletes sustained during routine CrossFit
      training. An online questionnaire was distributed amongst international CrossFit
      online forums. Data collected included general demographics, training programs,
      injury profiles and supplement use. A total of 132 responses were collected with
      97 (73.5%) having sustained an injury during CrossFit training. A total of 186
      injuries were reported with 9 (7.0%) requiring surgical intervention. An injury
      rate of 3.1 per 1000 hours trained was calculated. No incidences of
      rhabdomyolysis were reported. Injury rates with CrossFit training are similar to
      that reported in the literature for sports such as Olympic weight-lifting, power
      lifting and gymnastics and lower than competitive contact sports such as rugby
      union and rugby league. Shoulder and spine injuries predominate with no
      incidences of rhabdomyolysis obtained. To our knowledge this is the first paper
      in the literature detailing the injury rates and profiles with CrossFit
      participation.

PMID- 24276295
TI  - Long-term effect of whole body vibration training on jump height: meta-analysis.
AB  - Whole body vibration (WBV) is widely promoted as a means of improving muscle
      strength, but the evidence of a performance benefit is unclear with some
      reporting improvements and others finding none. The objective of this study was
      to analyze the current evidence for the effectiveness of WBV on jump height. We
      included randomized controlled trials or matched design studies comparing the
      effect of WBV training on countermovement and squat jump (SJ) height, which were
      gathered from MEDLINE, Web of Knowledge, Sciencedirect, Proquest, Scopus, Google
      Scholar, and SPORTDiscus databases. The overall effect of WBV training (from the
      15 studies included) compared with having no additional exercise on
      countermovement jump height yielded a positive standardized mean difference of
      0.77 (95% confidence interval, 0.55-0.99). The effect of WBV training on SJ
      height was 0.68 (0.08-1.11). Vibration exercise consisting of a higher frequency
      (>30 Hz, 0.86, 0.62-1.10), higher amplitude (>3 mm, 0.84, 0.52-1.17), longer
      exposure duration (>10 minutes per session, 0.92, 0.48-1.36), longer training
      period (>12 weeks, 0.87, 0.56-1.19) and among nonathletes (0.96, 0.63-1.30) had
      greater benefit for jump height improvement than a lower frequency (<= 30 Hz,
      0.56, 0.13-0.99), lower amplitude (<= 3 mm, 0.66, 0.35-0.98), shorter exposure
      duration (<= 10 minutes per session, 0.68, 0.45-0.92), intermediate training
      period (4-12 weeks, 0.72, 0.35-1.09), shorter training period (<4 weeks, 0.58, 
      0.08 to -1.23) and in athletes (0.59, 0.31-0.88). The effect of WBV training
      compared with a standard cardiovascular-type exercise group from 4 studies was
      0.63 (0.10-1.15). In conclusion, WBV training produces a moderate-to-large effect
      on jump height. Vibration training protocols with higher frequencies, higher
      amplitudes, longer exposures per session, and longer training periods are more
      likely to enhance muscle power.

PMID- 24276296
TI  - High intensity training and energy production during 90-second box jump in junior
      alpine skiers.
AB  - Alpine ski races can last up to 2.5 minutes and have very high metabolic demands.
      One limiting factor for performance is insufficient aerobic energy supply. We
      studied the effects of an 8-day interval training block on aerobic capacity
      (VO2max) and performance and physiology during the 90-second box jump test
      (BJ90), a maximal performance test employed to simulate the metabolic demands of
      alpine ski racing, in elite junior skiers. After 10 high-intensity interval
      training sessions, performed as cycling, running, or an obstacle course, VO2max
      increased in all subjects by 2.5 +/- 1.9 ml . minute(-1) . kg(-1) (4.3 +/- 3.2%),
      as did maximal blood lactate concentration in a graded cycling test (before: 11.7
      +/- 1.3 mmol . L(-1), after: 14.8 +/- 1.8 mmol . L(-1), both parameters p <=
      0.05). Performance (total jumps) and aerobic energy contribution (63.3 +/- 2.8%)
      during the BJ90 did not increase as hypothesized; however, subjects altered their
      pacing strategy, which may have counteracted such an effect. Additionally, the
      present data support the practicality of the performance test used for mimicking
      the demands of alpine skiing.

PMID- 24276297
TI  - Intrasession and intersession reliability in maximal and explosive isometric
      torque production of the elbow flexors.
AB  - The purpose of this study was to assess intrasession and intersession reliability
      of maximal and explosive isometric torque production of the elbow flexors and its
      respective neuromuscular activation pattern. Subjects (13 men, age: 24.8 +/- 3.1
      years, height: 1.9 +/- 0.1 m, body mass: 83.7 +/- 12.7 kg; and 6 women, age: 26.5
      +/- 1.4 years, height: 1.7 +/- 0.1 m, body mass: 62.7 +/- 7.0 kg) were tested and
      retested 2-7 days later performing unilateral maximal isometric elbow flexions.
      Absolute (coefficient of variation [CV], test-retest variability [TRV], Bland
      Altman plots with 95% limits of agreement) and relative reliability statistics
      (intraclass correlation coefficient) were calculated for various mechanical
      (i.e., maximal isometric torque, rate of torque development, impulse) and
      electromyographical measures (i.e., mean average voltage) at different time
      intervals relative to onset of torque (i.e., 30, 50, 100, 200, 300, 400, 100-200
      ms). Intraclass correlation coefficient values were >= 0.61 for all mechanical
      and electromyographical measures and time intervals indicating good to excellent
      intrasession and intersession reliability. Bland-Altman plots confirmed these
      findings by showing that only 0-2 (<= 13.3%) data points were beyond the limits
      of agreement. Regarding torque and electromyographic measures, CV (11.9-32.3%)
      and TRV (18.4-53.8%) values were high during the early intervals of torque
      development (<= 100 ms) indicating high variability. During the later intervals
      (>100 ms), lower CV (i.e., 5.0-29.9%) and TRV values (i.e., 5.4-34.6%) were
      observed indicating lower variability. The present study revealed that
      neuromuscular performance during explosive torque production of the elbow flexors
      is reproducible in time intervals >100 ms after onset of isometric actions,
      whereas during earlier time intervals variability is high.

PMID- 24276298
TI  - Development of a criterion method to determine peak mechanical power output in a
      countermovement jump.
AB  - There is a general agreement that the most valid method of measuring peak lower
      body mechanical power output (LBPP) in a countermovement jump (CMJ) is by
      analysis of the corresponding vertical component of the ground reaction force
      (VGRF)-time history of the jump. However, there is no published standard
      protocol. The purpose of this study was to establish a standard protocol. The
      variables necessary to define a valid and reliable CMJ method were: (a) vertical
      force range, (b) force sampling and integration frequency, (c) method of
      integration, (d) determination of body weight (BW), and (e) determination of the
      initiation of the CMJ. Countermovement jumps off a force platform (FP) were
      performed by 15 male professional rugby players. The 5 variables were then
      optimized to maximize the reliability and validity of the measure of LBPP. Errors
      of <1% (p <= 0.05) in the measurement of LBPP were obtained using the following
      specification: (a) 6 times BW (using a 16-bit analog to digital converter), (b)
      1,000 Hz, (c) Simpson's rule or the trapezoidal rule, (d) mean VGRF for 1 second
      of quiet standing immediately before jump signal, and (e) 30 ms before the
      instant BW +/- 5 SD is exceeded after the jump signal. Peak lower-body power
      output was most sensitive to variables 4 and 5. It was concluded that this study
      has established a standard protocol for the criterion method of measuring peak
      power in a CMJ using an FP. As all other estimates and less reliable methods of
      determining LBPP in a CMJ rely on the FP method for calibration, it is proposed
      that this protocol be used as the basis of future criterion measures using a FP.

PMID- 24276299
TI  - The effect of exercise intensity on postresistance exercise hypotension in
      trained men.
AB  - The occurrence of postresistance exercise hypotension (PEH) after resistance
      exercise remains unknown. This study examined blood pressure and heart rate (HR)
      responses to an acute bout of low- and high-intensity resistance exercise,
      matched for total work, in trained males. Sixteen resistance-trained males (23.1
      +/- 5.9 years) performed an acute bout of low- (40% of 1 repetition maximum
      [1RM]) and high-intensity resistance exercise (80% 1RM), matched for total work,
      separated by 7 days and performed in a counterbalanced order. Systolic blood
      pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP),
      and HR were assessed before exercise, after completion of each exercise
      resistance exercise (3 sets of back squat, bench press, and deadlift) and every
      10 minutes after resistance exercise for a period of 60 minutes. Results
      indicated a significant intensity * time interaction for SBP (p = 0.034, partial
      eta(2) = 0.122) and MAP (p = 0.047, partial eta(2) = 0.116) whereby SBP and MAP
      at 50-minute recovery and 60-minute recovery were significantly lower after high
      intensity exercise (p = 0.01 for SBP and p = 0.05 for MAP in both cases) compared
      with low-intensity exercise. There were no significant main effects or
      interactions in regard to DBP (all p > 0.05). Heart rate data indicated a
      significant main effect for time (F(9, 135) = 2.479, p = 0.0001, partial eta(2) =
      0.344). Post hoc multiple comparisons indicated that HR was significantly higher
      after squat, bench press, and deadlift exercise compared with resting HR and HR
      at 40-, 50-, and 60-minute recovery (all p = 0.03). The present findings suggest
      that an acute bout of high intensity, but not low intensity, resistance exercise
      using compound movements can promote PEH in trained men.

PMID- 24276300
TI  - Validity and interunit reliability of 10 Hz and 15 Hz GPS units for assessing
      athlete movement demands.
AB  - The purpose of this study was to assess the validity and interunit reliability of
      10 Hz (Catapult) and 15 Hz (GPSports) Global Positioning System (GPS) units and
      investigate the differences between these units as measures of team sport athlete
      movement demands. A team sport simulation circuit was completed by 8 trained male
      participants. The movement demands examined included: total distance covered
      (TD), average peak speed, and the distance covered, time spent, and the number of
      efforts performed low-speed running (0.00-13.99 km . h(-1)), high-speed running
      (14.00-19.99 km . h(-1)), and very high-speed running (>20.00 km . h(-1)). The
      degree of difference between the 10 Hz and the 15 Hz GPS units and validity was
      assessed using a paired samples t-test. Pearson's correlations were also used for
      validity assessment. Interunit reliability was established using percentage
      typical error of measurement (%TEM) and intraclass correlations. The findings
      revealed that 10 Hz GPS units were a valid (p > 0.05) and reliable (%TEM = 1.3%)
      measure of TD. In contrast, the 15 Hz GPS units exhibited lower validity for TD
      and average peak speed. Further, as the speed of movement increased the level of
      error for the 10 Hz and 15 Hz GPS units increased (%TEM = 0.8-19.9). The findings
      from this study suggest that comparisons should not be undertaken between 10 Hz
      and 15 Hz GPS units. In general, the 10 Hz GPS units measured movement demands
      with greater validity and interunit reliability than the 15 Hz units, however,
      both 10 Hz and 15 Hz units provided the improved measures of movement demands in
      comparison to 1 Hz and 5 Hz GPS units.

PMID- 24276301
TI  - Correspondence between training load executed by volleyball players and the one
      observed by coaches.
AB  - The main aim of this study was to compare the training load (TL) executed by
      volleyball players with that observed by coaches. Second, we analyzed the
      influence of the coaches' experience in the estimated TL. Twelve female
      volleyball players and 4 male coaches participated in this study. During a period
      of 15 weeks, physical (PT) and technical-tactical training sessions and matches
      were monitored. In each session, the session rating of perceived exertion (sRPE)
      was recorded to analyze the players' exercise intensity and TL(RP)E. Coaches were
      present in all sessions and rated their estimate of sRPE at the same time as the
      players to calculate the coaches' TL(RPE). Both players' and coaches' mean sRPE
      (4.0 +/- 1.1, 3.7 +/- 1.1, and 3.8 +/- 1.0 in players and expert and beginning
      coaches, respectively) and TLRPE (380.1 +/- 106.8, 358.3 +/- 110.5, and 359.7 +/-
      108.0 in players and expert and beginning coaches, respectively) were similar.
      However, a higher (p < 0.01) sRPE and TL(RPE) were observed in the players during
      PT. In general, the weekly TL(RPE) variation over the course of this study was
      similar in players and coaches. The players' sRPE and TL(RPE) were correlated (p
      < 0.01) with expert and beginner coaches' RPE (r = 0.70 and 0.72, respectively)
      and TL(RPE) (r = 0.75 and 0.76, respectively). In conclusion, the present
      findings show the correspondence between players' and coaches' sRPE and TL(RPE)
      regardless of their experience. Hence, coaches' TL(RPE) could be a useful and
      practical method to monitor and control the TL and other derived parameters in an
      easy way during volleyball.

PMID- 24276302
TI  - The influence of athletic status on the passive properties of the muscle-tendon
      unit and traditional performance measures in division I female soccer players and
      nonathlete controls.
AB  - The purpose of this study was to determine if passive muscle-tendon properties of
      the posterior muscles of the hip and thigh and lower-body muscle power could
      discriminate between athletic status in division I female soccer athletes and
      nonathlete controls. Ten athletes (mean +/- SE, age = 18.70 +/- 0.34 years; mass
      = 64.61 +/- 2.16 kg; height = 165.99 +/- 1.46 cm; thigh muscle cross-sectional
      area = 94.08 +/- 2.58 cm) and 11 nonathletes (mean +/- SE, age = 19.64 +/- 0.51
      years; mass = 62.81 +/- 2.60 kg; height = 162.44 +/- 2.20 cm; thigh muscle cross
      sectional area = 86.33 +/- 2.81 cm) performed 2 instrumented straight-leg raise
      (iSLR) assessments using an isokinetic dynamometer programmed in passive mode to
      move the foot toward the head at 5 degrees .s. During each iSLR, passive
      stiffness was calculated from the slopes of the initial (phase 1) and final
      (phase 2) portions of the angle-torque curve, and maximum range of motion (ROM)
      was determined as the point of discomfort but not pain, as indicated by the
      participant. Lower-body power characteristics were assessed through a
      countermovement vertical jump (CMJ) test. The results indicated that phase 1 and
      2 slopes, CMJ height, and peak power (Pmax) were significantly higher (p = 0.004
      0.036) for the athletes compared with the nonathletes; however, maximum ROM was
      not different (p = 0.601) between groups. Significant relationships were also
      observed between phase 1 and 2 slopes, and CMJ height and Pmax (r = 0.483-0.827;
      p <= 0.001-0.027). These findings suggest that in addition to traditional power
      characteristics, passive stiffness may also be a sensitive and effective measure
      for discriminating athletes from nonathletes. Coaches and practitioners may use
      these findings when designing training programs aimed at increasing
      musculotendinous stiffness of the posterior hip and thigh muscles and to help
      identify athletes with high overall athletic potential.

PMID- 24276303
TI  - Effect of supervised, periodized exercise training vs. self-directed training on
      lean body mass and other fitness variables in health club members.
AB  - Conventional wisdom suggests that exercise training with a personal trainer (PTr)
      is more beneficial for improving health-related fitness than training alone.
      However, there are no published data that confirm whether fitness club members
      who exercise with a PTr in the fitness club setting obtain superior results
      compared with self-directed training. We hypothesized that club members
      randomized to receive an evidence-based training program would accrue greater
      improvements in lean body mass (LBM) and other fitness measures than members
      randomized to self-training. Men, aged 30-44 years, who were members of a single
      Southern California fitness club were randomized to exercise with a PTr
      administering a nonlinear periodized training program (TRAINED, N = 17) or to
      self-directed training (SELF, N = 17); both groups trained 3 days per week for 12
      weeks. Lean body mass was determined by dual-energy x-ray absorptiometry.
      Secondary outcomes included muscle strength 1 repetition maximum (1RM), leg power
      (vertical jump), and aerobic capacity (V[Combining Dot Above]O2max). TRAINED
      individuals increased LBM by 1.3 (0.4) kg, mean (SEM) vs. no change in SELF, p =
      0.029. Similarly, significantly greater improvements were seen for TRAINED vs.
      SELF in chest press strength (42 vs. 19%; p = 0.003), peak leg power (6 vs. 0.6%;
      p < 0.0001), and V[Combining Dot Above]O2max (7 vs. -0.3%; p = 0.01). Leg press
      strength improved 38 and 25% in TRAINED and SELF, respectively (p = 0.14). We
      have demonstrated for the first time in a fitness club setting that members whose
      training is directed by well-qualified PTrs administering evidence-based training
      regimens achieve significantly greater improvements in LBM and other dimensions
      of fitness than members who direct their own training.

PMID- 24276304
TI  - beta-Alanine supplementation for athletic performance: an update.
AB  - beta-alanine supplementation has become a common practice among competitive
      athletes participating in a range of different sports. Although the mechanism by
      which chronic beta-alanine supplementation could have an ergogenic effect is
      widely debated, the popular view is that beta-alanine supplementation augments
      intramuscular carnosine content, leading to an increase in muscle buffer
      capacity, a delay in the onset of muscular fatigue, and a facilitated recovery
      during repeated bouts of high-intensity exercise. beta-alanine supplementation
      appears to be most effective for exercise tasks that rely heavily on ATP
      synthesis from anaerobic glycolysis. However, research investigating its efficacy
      as an ergogenic aid remains equivocal, making it difficult to draw conclusions as
      to its effectiveness for training and competition. The aim of this review was to
      update, summarize, and critically evaluate the findings associated with beta
      alanine supplementation and exercise performance with the most recent research
      available to allow the development of practical recommendations for coaches and
      athletes. A critical review of the literature reveals that when significant
      ergogenic effects have been found, they have been generally shown in untrained
      individuals performing exercise bouts under laboratory conditions. The body of
      scientific data available concerning highly trained athletes performing single
      competition-like exercise tasks indicates that this type of population receives
      modest but potentially worthwhile performance benefits from beta-alanine
      supplementation. Recent data indicate that athletes may not only be using beta
      alanine supplementation to enhance sports performance but also as a training aid
      to augment bouts of high-intensity training. beta-alanine supplementation has
      also been shown to increase resistance training performance and training volume
      in team-sport athletes, which may allow for greater overload and superior
      adaptations compared with training alone. The ergogenic potential of beta-alanine
      supplementation for elite athletes performing repeated high-intensity exercise
      bouts, either during training or during competition in sports which require
      repeated maximal efforts (e.g., rugby and soccer), needs scientific confirmation.

PMID- 24276305
TI  - The acute hormonal response to free weight and machine weight resistance
      exercise.
AB  - Resistance exercise can acutely increase the concentrations of circulating
      neuroendocrine factors, but the effect of mode on this response is not
      established. The purpose of this study was to examine the effect of resistance
      exercise selection on the acute hormonal response using similar lower-body
      multijoint movement free weight and machine weight exercises. Ten resistance
      trained men (25 +/- 3 years, 179 +/- 7 cm, 84.2 +/- 10.5 kg) completed 6 sets of
      10 repetitions of squat or leg press at the same relative intensity separated by
      1 week. Blood samples were collected before (PRE), immediately after (IP), and 15
      (P15) and 30 minutes (P30) after exercise, and analyzed for testosterone (T),
      growth hormone (GH), and cortisol (C) concentrations. Exercise increased (p <=
      0.05) T and GH at IP, but the concentrations at IP were greater for the squat (T:
      31.4 +/- 10.3 nmol.L(-1); GH: 9.5 +/- 7.3 MUg.L(-1)) than for the leg press (T:
      26.9 +/- 7.8 nmol.L(-1); GH: 2.8 +/- 3.2 MUg.L(-1)). At P15 and P30, GH was
      greater for the squat (P15: 12.3 +/- 8.9 MUg.L(-1); P30: 12.0 +/- 8.9 MUg.L(-1))
      than for the leg press (P15: 4.8 +/- 3.4 MUg.L(-1); P30: 5.4 +/- 4.1 MUg.L(-1)).
      C was increased after exercise and was greater for the squat than for the leg
      press. Although total work (external load and body mass moved) was greater for
      the squat than for the leg press, rating of perceived exertion did not differ
      between the modes. Free weight exercises seem to induce greater hormonal
      responses to resistance exercise than machine weight exercises using similar
      lower-body multijoint movements and primary movers.

PMID- 24276306
TI  - The influence of age on the viscoelastic stretch response.
AB  - Passive stretching is commonly recommended to help reduce passive stiffness in
      older adults, yet their acute viscoelastic stretch responses are still unclear.
      The purpose of this study was to determine the influence of age on the acute
      viscoelastic responses to a practical stretching intervention. Twenty-two younger
      (24 +/- 3 years) and 14 older (67 +/- 3 years) males performed four 30-second
      passive stretches of the plantar flexors at a predetermined torque threshold. The
      absolute and relative change in stress relaxation (decline in torque during each
      30-second stretch) and creep (increase in ankle joint angle across the 4
      stretches) were recorded. Passive stiffness was calculated as the slope of the
      angle-torque curve at 10 degrees  angle of dorsiflexion. There were no
      differences for the absolute stress relaxation responses (p >= 0.118); however,
      the relative change in stress relaxation was greater (p = 0.010) for the younger
      vs. older men at stretch 1 (13.0 vs. 8.6%) and decreased across stretches for the
      younger men (stretch 1 > 3 and 4; p <= 0.018), whereas the older men demonstrated
      a similar relative change across all 4 stretches (p = 0.917). No age related
      differences were found for either the absolute or relative creep responses (p >=
      0.072). Passive stiffness was also greater in the older men (p = 0.044). These
      results suggest that the younger men displayed a greater initial relative stress
      relaxation response that diminished across the repeated stretches, whereas the
      older men experienced a smaller relative response that remained constant across
      the four 30-second stretches. However, the increase in range of motion for a
      given stretch torque (creep) across all 4 stretches was similar between groups
      despite differences in passive stiffness.

PMID- 24276307
TI  - Use of heart rate variability in monitoring stress and recovery in judo athletes.
AB  - The main objective of this study was to examine the effect of different judo
      training loads on heart rate variability (HRV) measurements, to determine if they
      can be used as valid indicators in monitoring stress and recovery in judo
      athletes. Fourteen male national-standard judo athletes were randomly divided
      into 2 groups, and each group followed a different type of training, namely, a
      high training load (HTL) and a moderate training load program (MTL). Data
      collection included HRV measurements, a Recovery Stress Questionnaire for
      athletes (RESTQ-SPORT), and strength measurements, 4 weeks before and after the
      training program. The HTL group had lower square root of the mean squared
      difference of successive RR intervals, very low frequency, high frequency, short
      term variability, short-range scaling exponents, general recovery, sport-specific
      recovery, general stress, maximum strength, maximum power, and higher low/high
      frequency ratio at posttest compared with pretest (p <= 0.05). The HTL group
      showed lower short-range and long-range scaling exponents, general recovery,
      sport-specific recovery, and higher general stress than the MTL group in posttest
      measurements (p <= 0.05). In conclusion, judo athletes enrolled in an HTL program
      showed an imbalance of the autonomic nervous system with decreased vagal
      modulation, together with a decrease in strength parameters, higher markers for
      stress, and a lower perception of recovery.

PMID- 24276308
TI  - Stride angle as a novel indicator of running economy in well-trained runners.
AB  - The main purpose of this study was to investigate the relationship between a
      novel biomechanical variable, the stride angle, and running economy (RE) in a
      homogeneous group of long-distance athletes. Twenty-five well-trained male
      runners completed 4-minute running stages on a treadmill at different set
      velocities. During the test, biomechanical variables such as stride angle, swing
      time, ground contact time, stride length, stride frequency, and the different sub
      phases of ground contact were recorded using an optical measurement system. VO2
      values at velocities below the lactate threshold were measured to calculate RE.
      Stride angle was negatively correlated with RE at every speed (p < 0.001, large
      effect sizes). Running economy was also negatively correlated with swing phase
      and positively correlated with ground contact time and running performance
      according to the best 10-km race time (p <= 0.05, moderate and large effect
      sizes). Last, stride angle was correlated with ground contact time at every speed
      (p < 0.001, large effect sizes). In conclusion, it seems that optimal execution
      of stride angle allows runners to minimize contact time during ground contact,
      whereby facilitating a better RE. Coaches and/or athletes may find stride angle a
      useful and easily obtainable measure to track and make alterations to running
      technique, because changes in stride angle may influence the energy cost of
      running and lead to improved performance.

PMID- 24276310
TI  - Predicting punching acceleration from selected strength and power variables in
      elite karate athletes: a multiple regression analysis.
AB  - This study investigated the relationship between punching acceleration and
      selected strength and power variables in 19 professional karate athletes from the
      Brazilian National Team (9 men and 10 women; age, 23 +/- 3 years; height, 1.71 +/
      0.09 m; and body mass [BM], 67.34 +/- 13.44 kg). Punching acceleration was
      assessed under 4 different conditions in a randomized order: (a) fixed distance
      aiming to attain maximum speed (FS), (b) fixed distance aiming to attain maximum
      impact (FI), (c) self-selected distance aiming to attain maximum speed, and (d)
      self-selected distance aiming to attain maximum impact. The selected strength and
      power variables were as follows: maximal dynamic strength in bench press and
      squat-machine, squat and countermovement jump height, mean propulsive power in
      bench throw and jump squat, and mean propulsive velocity in jump squat with 40%
      of BM. Upper- and lower-body power and maximal dynamic strength variables were
      positively correlated to punch acceleration in all conditions. Multiple
      regression analysis also revealed predictive variables: relative mean propulsive
      power in squat jump (W.kg-1), and maximal dynamic strength 1 repetition maximum
      in both bench press and squat-machine exercises. An impact-oriented instruction
      and a self-selected distance to start the movement seem to be crucial to reach
      the highest acceleration during punching execution. This investigation, while
      demonstrating strong correlations between punching acceleration and strength
      power variables, also provides important information for coaches, especially for
      designing better training strategies to improve punching speed.

PMID- 24276311
TI  - Comparing one repetition maximum and three repetition maximum between
      conventional and eccentrically loaded deadlifts.
AB  - This study determined if an eccentrically loaded deadlift yields a higher 1
      repetition maximum (1RM) and 3RM than a conventional deadlift and if the 1RM
      conventional and eccentrically loaded deadlift can be accurately estimated from
      the 3RM (3RM = 93% of 1RM). Division 1 football players (n = 15; 20.3 +/- 1.9
      years; 95.8 +/- 18.2 kg; 184.4 +/- 6.6 cm) participated. Deadlift 1RM and 3RM
      were measured in the conventional and eccentrically loaded deadlift. Dependent t
      tests showed no significant difference between the 3RM and 1RM conventional
      deadlift and the 3RM and 1RM eccentrically loaded deadlift (p = 0.30 and p =
      0.20, respectively). Pearson correlation between the 1RM conventional deadlift
      estimate and 1RM conventional deadlift actual was r = 0.91 (p <= 0.01); a
      dependent t-test indicated the 1RM conventional deadlift estimate was
      significantly less than the 1RM conventional deadlift actual (p = 0.007). Pearson
      correlation between the 1RM eccentrically loaded deadlift estimate and 1RM
      eccentrically loaded deadlift actual was r = 0.84 (p <= 0.01); a dependent t-test
      indicated the 1RM eccentrically loaded deadlift estimate was nearly significantly
      less than the 1RM eccentrically loaded deadlift actual (p = 0.061). Results
      suggest that conventional and eccentrically loaded deadlifts may be
      interchangeable within a training program; this may elicit the benefits of using
      a broader variety of ground-based multijoint compound movements in an athlete's
      strength and power training. Additionally, because of differences between
      predicted and actual 1RM scores in the deadlift, strength coaches should
      prioritize actual 1RM testing of their athletes to optimize deadlift training
      loads across the RM continuum.

PMID- 24276312
TI  - The background is remapped across saccades.
AB  - Physiological studies have found that neurons prepare for impending eye
      movements, showing anticipatory responses to stimuli presented at the location of
      the post-saccadic receptive fields (RFs) (Wurtz in Vis Res 48:2070-2089, 2008).
      These studies proposed that visual neurons with shifting RFs prepared for the
      stimuli they would process after an impending saccade. Additionally,
      psychophysical studies have shown behavioral consequences of those anticipatory
      responses, including the transfer of aftereffects (Melcher in Nat Neurosci 10:903
      907, 2007) and the remapping of attention (Rolfs et al. in Nat Neurosci 14:252
      258, 2011). As the physiological studies proposed, the shifting RF mechanism
      explains the transfer of aftereffects. Recently, a new mechanism based on
      activation transfer via a saliency map was proposed, which accounted for the
      remapping of attention (Cavanagh et al. in Trends Cogn Sci 14:147-153, 2010). We
      hypothesized that there would be different aspects of the remapping corresponding
      to these different neural mechanisms. This study found that the information in
      the background was remapped to a similar extent as the figure, provided that the
      visual context remained stable. We manipulated the status of the figure and the
      ground in the saliency map and showed that the manipulation modulated the
      remapping of the figure and the ground in different ways. These results suggest
      that the visual system has an ability to remap the background as well as the
      figure, but lacks the ability to modulate the remapping of the background based
      on the visual context, and that different neural mechanisms might work together
      to maintain visual stability across saccades. 

PMID- 24276313
TI  - Haptic guidance interferes with learning to make movements at an angle to
      stimulus direction.
AB  - Haptic guidance has been shown to interfere with learning a novel visuo-motor
      rotation. Here, we ask whether this interference is specific to the learning of
      visuo-motor transformations or whether it is a more generalized phenomenon of
      learning spatial movement characteristics. Participants practiced to make
      movements at an angle of 75 degrees  relative to target directions with and
      without haptic path guidance. Test trials without guidance and without visual
      feedback revealed poorer performance after haptic guidance practice than in the
      no-guidance control group, even though during guided practice movement directions
      were more accurate than during unguided practice. The more precise directions
      during guided practice were associated with shorter movement latencies than in
      the control group, suggesting an incomplete rotation of the movement direction
      relative to the direction of the visual target. A detailed analysis of the first
      few millimeters of each movement revealed that the initial movement direction was
      indeed rotated too little, and the correct direction was adopted only gradually
      under the influence of haptic guidance. These findings support the perspective on
      motor learning as a process that is driven by consequent improvements of
      performance and that is compromised by factors that serve to improve performance
      even without learning. Haptic guidance is one such factor. 

PMID- 24276314
TI  - Analgesia to pressure-pain develops in the ipsilateral forehead after high- and
      low-frequency electrical stimulation of the forearm.
AB  - In healthy participants, high-frequency electrical stimulation of the forearm not
      only evokes local hyperalgesia but also inhibits sensitivity to pressure-pain in
      the ipsilateral forehead, possibly due to activation of ipsilateral inhibitory
      pain modulation processes. The aim of this study was to compare the effects of
      high- and low-frequency electrical stimulation of the forearm on sensitivity to
      pressure-pain in the ipsilateral forehead, as inhibitory pain modulation may be
      stronger after low- than high-frequency electrical stimulation. Before and after
      high- and low-frequency electrical stimulation, sensitivity to heat and to blunt
      and sharp stimuli was assessed at and adjacent to the electrically conditioned
      site in the forearm. In addition, sensitivity to blunt pressure was measured
      bilaterally in the forehead. Pain was more intense after high- than low-frequency
      electrical stimulation and was followed by primary and secondary hyperalgesia to
      mechanical stimulation after high- but not low-frequency electrical stimulation.
      Nevertheless, sensitivity to pressure-pain decreased to the same extent in the
      ipsilateral forehead after both forms of electrical stimulation. This decrease
      was associated with heightened sensitivity to pressure-pain at the electrically
      conditioned forearm site and with diminished sensitivity to heat around this
      site. These findings suggest that sensitisation of pressure-sensitive nociceptive
      afferents at the site of electrical stimulation is associated with generation of
      an ipsilateral pain-inhibitory process. This ipsilateral pain-inhibitory process
      may decrease sensitivity to pressure-pain in the ipsilateral forehead and
      suppress secondary hyperalgesia to heat. 

PMID- 24276317
TI  - Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study.
AB  - Some compounds articulated around a piperazine or an ethylenediamine linker have
      been evaluated in vitro to determine their activity in the presence of a 3T6
      fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively.
      The most efficient antifungal derivatives, namely N,N'-bis(benzamidine-4
      yl)ethane-1,2-diamine (compound 6, a diamidine) and N-(benzamidine-4-yl)-N'
      phenylethane-1,2-diamine (compound 7, a monoamidine), exhibited no cytotoxicity
      and were evaluated in vivo in a rat model. Only the diamidine 6 emerged as a
      promising hit for further studies. 

PMID- 24276316
TI  - Current Challenges and Future Directions in Recombinant AAV-Mediated Gene Therapy
      of Duchenne Muscular Dystrophy.
AB  - Various characteristics of adeno-associated virus (AAV)-based vectors with long
      term safe expression have made it an exciting transduction tool for clinical gene
      therapy of Duchenne muscular dystrophy (DMD). Although host immune reactions
      against the vector as well as transgene products were detected in some instances
      of the clinical studies, there have been promising observations. Methods of
      producing AAV vectors for considerable in vivo experimentation and clinical
      investigations have been developed and a number of studies with AAV vector
      mediated muscle transduction were attempted. Notably, an intravenous limb
      perfusion transduction technique enables extensive transgene expression in the
      skeletal muscles without noticeable adverse events. Furthermore, cardiac
      transduction by the rAAV9-microdystrophin would be promising to prevent
      development of cardiac dysfunction. Recent achievements in transduction
      technology suggest that long-term transgene expression with therapeutic benefits
      in DMD treatment would be achieved by the rAAV-mediated transduction strategy
      with an adequate regimen to regulate host immune response. 

PMID- 24276315
TI  - Voltage-gated calcium channel antagonists and traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability in the
      United States. Despite more than 30 years of research, no pharmacological agents
      have been identified that improve neurological function following TBI. However,
      several lines of research described in this review provide support for further
      development of voltage gated calcium channel (VGCC) antagonists as potential
      therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and
      sometimes enduring increase in intracellular calcium ([Ca2+]i). These fluxes in
      [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to
      long-term cell dysfunction in surviving cells. In a limited number of in vitro
      experiments, both L-type and N-type VGCC antagonists successfully reduced calcium
      loads as well as neuronal and astrocytic cell death following mechanical injury.
      In rodent models of TBI, administration of VGCC antagonists reduced cell death
      and improved cognitive function. It is clear that there is a critical need to
      find effective therapeutics and rational drug delivery strategies for the
      management and treatment of TBI, and we believe that further investigation of
      VGCC antagonists should be pursued before ruling out the possibility of
      successful translation to the clinic. 

PMID- 24276318
TI  - Role of diuretics and ultrafiltration in congestive heart failure.
AB  - Volume overload in heart failure (HF) results from neurohumoral activation
      causing renal sodium and water retention secondary to arterial underfilling.
      Volume overload not only causes signs and symptoms of congestion, but can impact
      myocardial remodeling and HF progression. Thus, treating congestion is a
      cornerstone of HF management. Loop diuretics are the most commonly used drugs in
      this setting. However, up to 30% of the patients with decompensated HF present
      with loop-diuretic resistance. A universally accepted definition of loop diuretic
      resistance, however, is lacking. Several approaches to treat diuretic-resistant
      HF are available, including addition of distal acting thiazide diuretics,
      natriuretic doses of mineralocorticoid receptor antagonists (MRAs), or vasoactive
      drugs. Slow continuous veno-venous ultrafiltration is another option.
      Ultrafiltration, if it is started early in the course of HF decompensation, may
      result in prominent decongestion and a reduction in re-hospitalization. On the
      other hand, ultrafiltration in HF patients with worsening renal function and
      volume overload after aggressive treatment with loop diuretics, failed to show
      benefit compared to a stepwise pharmacological approach, including diuretics and
      vasoactive drugs. Early detection of congested HF patients for ultrafiltration
      treatment might improve decongestion and reduce readmission. However, the best
      patient characteristics and best timing of ultrafiltration requires further
      evaluation in randomized controlled studies. 

PMID- 24276319
TI  - Protein-based blood substitutes: recent attempts at controlling pro-oxidant
      reactivity with and beyond hemoglobin.
AB  - Reviewed here are recent attempts to produce protein-based artificial oxygen
      carriers ("blood substitutes"). Most of these involve chemical or physical
      modifications on hemoglobin, although a recent line of research using hemerythrin
      instead of hemoglobin is also described. The focus is set on the extent to which
      these modifications alter the redox reactivity of the proteins, and on ways in
      which this can be done systematically and purposefully, within the framework of a
      working hypothesis where redox side-reactions hold an important role in the
      physiological outcome of experimental transfusions with artificial oxygen
      carriers. 

PMID- 24276321
TI  - Breeding for resistance to diseases in greengram and blackgram.
AB  - This review is given on the origin and interrelationship of blackgram and
      greengram: the symptoms, mode of transmission, and host range of important
      diseases, namely: mungbean yellow mosaic virus, leaf crinkle virus, leaf curl
      virus, mosaic mottle virus, Cercospora leaf spot, powdery mildew, root and stem
      rots, bacterial leaf spot and halo blight. The screening for resistance, sources
      of resistance, including interspecific hybridization, and induced mutations, as
      well as the genetics of resistance are treated along with suggestions for future
      breeding strategies of these crops. 

PMID- 24276322
TI  - X-ray irradiation of excised embryos of mesta (Hibiscus cannabinus L. and H.
      sabdariffa L.).
AB  - Excised embryos of Hibiscus spp. were treated with 1 kR to 6 kR of X-ray. Results
      indicate that germination was unaffected at this level of employed doses in both
      species, which in turn implies that the factors responsible for inhibition of
      germination are not present in the embryo. LD50 values differed between varieties
      and species. Early varieties of both species were more sensitive to radiation
      than late varieties. Strikingly similar effects were observed for the varieties
      with smaller embryos over those with larger ones. Allopolyploid H. sabdariffa
      (2n=72) was more susceptible than diploid H. cannabinus (2n=36).Differences in
      mutation frequency exist between species with different levels of ploidy and
      between varieties within the same species. Most of the HC mesta varieties yielded
      higher mutation frequencies than those of HS mesta. Optimal dose for triggering
      mutations in all varieties (except the chlorophyll mutation variety of HC mesta)
      of the two species lies within a narrow range of 1 kR to 2 kR. Cent per cent
      seedling abnormalities is concomitant to LD50; nevertheless, optimum dose for
      mutation frequency is independent of LD50. Hence, the response should be viewed
      in terms of respective genotype. The advantages of the embryo irradiation
      technique are mentioned. 

PMID- 24276323
TI  - Genetics of the sex ratio anomaly in Drosophila hybrids of the Virilis group.
AB  - A study was made of the effect of genotype and temperature (25 and 17 degrees C)
      on sex ratio in the hybrids D. virilis Sturt. X D. littoralis Sokolov. A genetic
      system has been found controlling sex-differential viability. In the F1 of the
      reciprocal hybrids D. virilis X D. littoralis the sex ratio is normal, though at
      17 degrees C females are slightly excessive. The abnormal sex ratio is observed
      only in the progeny of test crosses.The major gene causing the death of female
      progeny of the cross ? [? (?, ? D. virilis x ?, ? D. littoralis) x ? D. virilis]
      x ? D. littoralis is located on chromosome 2 of D. virilis. It is expressed as a
      lethal if chromosome 5 is heterogeneous virilis-littoralis. Chromosome 3 of D.
      virilis bears a modifier-enhancer and chromosome 5, a suppressor, of this lethal
      found in chromosome 2. This genetic system has a maternal effect and functions at
      25 degrees C, interacting with the X-chromosome of D. littoralis. If the
      maintainance temperature is lowered to 17 degrees C, the progeny of the cross
      'hybrid ? FB1 x ? D. littoralis' is predominantly female. Partial death of males
      is accounted for by a disturbance in the interaction between the genes of X
      chromosome in certain combinations with the D. virilis autosomes and the Y
      chromosome of the paternal species D. littoralis.Sex-differential mortality in
      the hybrids D. virilis x D. littoralis is one of the isolating factors between
      these species which does not appear to act until the second and subsequent F1
      generations due to the formation of the recombination load. 

PMID- 24276324
TI  - Genetic sexing in Drosophila melanogaster using the alcohol dehydrogenase locus
      and a Y-linked translocation.
AB  - By incorporating ethanol (4% v/v) into the larval rearing medium of a specially
      constructed Drosophila melanogaster strain it was possible to produce only male
      adults; the female larvae died.In this strain, the male determining chromosome
      was linked with a positive Alcohol dehydrogenase (ADH) allele by a translocation.
      The females were homozygous for the null allele and hence sensitive to
      ethanol.This genetic sexing method is discussed in relation to its use in the
      genetic control of insects. 

PMID- 24276320
TI  - New aspects of gene-silencing for the treatment of cardiovascular diseases.
AB  - Coronary heart disease (CHD), mainly caused by atherosclerosis, represents the
      single leading cause of death in industrialized countries. Besides the classical
      interventional therapies new applications for treatment of vascular wall
      pathologies are appearing on the horizon. RNA interference (RNAi) represents a
      novel therapeutic strategy due to sequence-specific gene-silencing through the
      use of small interfering RNA (siRNA). The modulation of gene expression by short
      RNAs provides a powerful tool to theoretically silence any disease-related or
      disease-promoting gene of interest. In this review we outline the RNAi
      mechanisms, the currently used delivery systems and their possible applications
      to the cardiovascular system. Especially, the optimization of the targeting and
      transfection procedures could enhance the efficiency of siRNA delivery
      drastically and might open the way to clinical applicability. The new findings of
      the last years may show the techniques to new innovative therapies and could
      probably play an important role in treating CHD in the future. 

PMID- 24276325
TI  - Chromosomal location of genes controlling seed proteins in species related to
      wheat.
AB  - The seed proteins of 'Chinese Spring' wheat stocks which possess single
      chromosomes from other plant species related to wheat have been separated by gel
      electrophoresis in the presence of sodium dodecyl sulphate. Marker protein bands
      have been detected for both arms of barley chromosome 5, chromosome E (= 1R) and
      B (= 2R) of rye, chromosomes A,B (= 1C(u)) and C (= 5C(u)) of Aegilops
      umbellulata and chromosomes I and III of Agropyron elongatum. These studies, and
      previous findings, indicate that chromosome 5 of barley, chromosome 1R of rye,
      chromosome I of Ag. elongatum and possibly chromosome 1C(u) of Ae. umbellulata
      are similar to chromosomes 1A, 1B and 1D in hexaploid wheat in that they carry
      genes controlling prolamins on their short arms and genes controlling high
      molecular-weight (apparent molecular weight greater than 86,000) seed protein
      species on their long arms. These findings support the idea that all these
      chromosomes are derived from a common ancestral chromosome and that they have
      maintained their integrity since their derivation from that ancestral chromosome.

PMID- 24276326
TI  - Identification of a 4A/7R and a 7B/4R wheat-rye chromosome translocation.
AB  - By producing chromosome substitutions with 'Imperial rye' chromosomes 4R (C) and
      7R (D) in the wheat cultivar 'Chinese Spring' two spontaneous translocation lines
      were obtained. One involves segments of wheat chromosome 4A and rye chromosome
      7R, the other involves portions of wheat chromosome 7B and rye chromosome 4R. 

PMID- 24276327
TI  - Characterization of the caryopsis of common wheat varieties and F2 generation
      hybrids by means of multivariate analysis.
AB  - Nineteen parameters of common wheat kernels were investigated by the multivariate
      procedure. A relationship between the DBC parameter and both specific gravity and
      kernel filling was found. In some populations an interdependence of the DBC
      parameter and the subaleurone endosperm thickness was found. In the analysis of
      principal components the DBC parameter was represented mostly by particular
      component. Significant dependences were found between the dimensions as well as
      the weight of the caryopsis and some dimensions of the crease and endosperm
      cavity. The dendrite constructed on the basis of the calculated Mahalanobis's
      generalized distances matrix represents the near affinity of reciprocal hybrids
      or pure lines originating from a single cultivar as well as hybrids and their
      parental forms. 

PMID- 24276328
TI  - Chromosome pairing in haploids of Brassica campestris.
AB  - The maximum chromosome pairing observed in haploids of Brassica campestris was
      two bivalents plus one trivalent but differences were observed in the chromosome
      pairing frequencies of the four haploids studied. This pairing supports the
      theorem that the species is hexasomic for one chromosome, tetrasomic for two and
      disomic for three others but it is emphasized that some of the observed pairing
      might be explained by a phenomenon other than homology. 

PMID- 24276329
TI  - Genetic-cytoplasmic male sterility in progeny of 4x-2x crosses in cultivated
      potatoes.
AB  - Forty-three percent of the progeny from 4x * 2x crosses [Group Tuberosum cultivar
      x diploid hybrid (Groups Phureja or Stenotomum x Group Tuberosum haploid)] were
      male sterile. In contrast only four percent of the progeny from the reciprocal
      crosses were male sterile. Male sterility among the former progeny is presumed to
      result from the interaction of Tuberosum cytoplasm with dominant genes from the
      cultivated diploids, Groups Phureja and Stenotomum, an interaction known to occur
      in crosses of Tuberosum haploid x cultivated diploid species (2n = 2x = 24). The
      frequency of fertile progeny from the 4x * 2x crosses (57%) was significantly
      higher than that from the 2x * 2x crosses (Tuberosum haploid x cultivated
      diploid), (28%). The frequency of male fertility among progeny from different
      cultivars in 4x * 2x crosses varied from 31-82 percent. The difference between
      cultivars strongly suggests that some cultivars may have dominant male fertility
      restorer genes. 

PMID- 24276330
TI  - Genetic variability of mineral concentrations in Festuca arundinacea Schreb.
AB  - Nine randomly chosen clones of tall fescue (Festuca arundinacea Schreb.) were
      mated in all possible combinations to determine the nature of genetic variation
      for Mg, Ca, K, and P concentrations in a broad genetic base population. General
      combining ability mean squares were significant for most variables, whereas
      specific combining ability mean squares were not significant in most instances
      indicating that additive genetic variance was more important. Genotype x year
      interactions were significant for most variables, suggesting that selection
      should be evaluated over many environments. Broad-sense heritability estimates
      based on parental and progeny variance components were generally high for P, K,
      Ca, and Mg but low for the ratio K/(Ca + Mg). Narrow-sense heritabilities for
      these minerals were close to the broad sense values since the additive genetic
      variance was the largest component of the total genetic variation. Correlations
      between mineral concentrations and herbage dry matter yield were low. It was
      concluded that adequate genetic variation exists to improve mineral concentration
      without altering herbage dry matter yields. 

PMID- 24276331
TI  - Characterization of the shear stress regulation of CD18 surface expression by
      HL60-derived neutrophil-like cells.
AB  - Shear stress-induced cleavage of cell surface CD18 integrins is reported to be
      part of an anti-inflammatory control mechanism that minimizes neutrophil activity
      in the blood under physiologic conditions. The cysteine protease, cathepsin B
      (catB), has been implicated in this mechanoregulatory mechanism, but its
      molecular dynamics remain to be elucidated. Moreover, attempts to do so using
      molecular approaches are hindered by the limited ex vivo life span of primary
      neutrophils. As an alternative, we explored the potential use of HL60-derived
      neutrophilic cells as a transfectable culture model that exhibits a shear-induced
      CD18 cleavage response comparable to primary neutrophils. HL60 cells were
      differentiated into neutrophil-like cells (dHL60-NCs) and exposed to laminar
      shear stress ([Formula: see text] for 10 min). Based on cytometric analyses,
      sheared cells cleaved CD18 and CD11a, but not CD11b, integrins. Treatment of
      cells with E64 or doxycycline prior to and during shear exposure inhibited CD18,
      but only attenuated CD11a, cleavage. Neither aprotinin nor pepstatin affected
      shear-induced CD18 or CD11a cleavage. Notably, dHL60-NCs expressed minimal catB.
      Thus, multiple cysteine proteases in addition to catB may cleave CD18 on sheared
      leukocytes. In fact, our findings indicate that multiple non-cysteine proteases
      also participate in the shear-related cleavage of CD11/CD18 heterodimers.
      Finally, shear-induced cleavage of CD18 and CD11a by dHL60-NCs was inhibited by
      fMLP concentrations of at least [Formula: see text]. Collectively, our findings
      indicate that shear-induced CD11/CD18 cleavage is phenotypic of neutrophilic
      cells, including those derived from HL60 cells. Moreover, our results verify
      shear stress as a key anti-inflammatory stimulus for neutrophils under
      physiologic conditions.

PMID- 24276332
TI  - Electrochemistry at nanometer-sized electrodes.
AB  - Electrodes of nanometer sizes provide a model approach to study the nanoscale
      electrochemical properties and processes, which are of fundamental and applied
      significance in a variety of areas including energy and environmental science,
      scanning probe microscopies, nanofabrication as well as electrochemistry itself.
      This Perspective reviews recent developments in conceptual understanding,
      theoretical modelling and simulation, and experimental observation of nanosize
      induced properties and phenomena at interfaces between nanometer-sized electrodes
      and electrolytes. The aim is to provide a view on how the dimension comparability
      of nanoelectrodes with the electric double layer and the effective electron
      tunnelling distance may raise distinct features in interfacial structure and
      reactivity. The strong coupling between the electrostatic field, the
      concentration field and the dielectric field of solvent at
      nanoelectrode/electrolyte interfaces is highlighted. The effects of this coupling
      on the voltammetric responses of nanoelectrodes are evaluated. Electron transfer
      kinetics at the nanoelectrode/electrolyte interface is discussed by emphasizing
      the inappropriateness of the Butler-Volmer (BV) and classic Marcus-Hush (MH)
      theories at potentials largely departing from the formal potential of the redox
      moieties and the importance of the long-distance electron tunnelling. The
      conditions for using the mathematically more straightforward BV and classic MH
      formalisms as an alternative to the physically more realistic but mathematically
      unfriendly Marcus-Hush-Chidsey model are analysed. 

PMID- 24276333
TI  - Feedback interaction of research, advocacy, and clinical care applied to ALS
      research in South America.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing motor
      neuron loss and weakness. Worldwide prevalence is 4-6/100,000. Incidence is 1.5
      2.7/100,000 per year and may be increasing. Studies suggest race and ethnicity
      affect the prevalence and incidence of ALS.(1) Understanding the impact of these
      variables on disease incidence could provide important insight into ALS
      determinants. A major roadblock for comparison across populations is the lack of
      epidemiologic data about ALS from many underdeveloped regions. In these regions,
      ALS is often undertreated due to health care disparities. This article discusses
      challenges for ALS research in South America (SA) and examines the ALS scientific
      record to explore the interactions and synergies of research, clinical care, and
      patient advocacy in underdeveloped regions. 

PMID- 24276334
TI  - Sonographic diagnosis of true neurogenic thoracic outlet syndrome.

PMID- 24276335
TI  - Distinction of seropositive NMO spectrum disorder and MS brain lesion
      distribution.

PMID- 24276336
TI  - Varicella-zoster virus acute myelitis in a patient with MS treated with
      natalizumab.

PMID- 24276337
TI  - Evidence-based guideline: Treatment of tardive syndromes: report of the Guideline
      Development Subcommittee of the American Academy of Neurology.

PMID- 24276338
TI  - Evidence-based guideline: Treatment of tardive syndromes: report of the Guideline
      Development Subcommittee of the American Academy of Neurology.

PMID- 24276339
TI  - Mystery case: Bilateral posterior periventricular heterotopias.

PMID- 24276340
TI  - Teaching neuroimages: conus medullaris involvement in cerebrospinal
      toxoplasmosis.

PMID- 24276341
TI  - Teaching neuroimages: combined retinal and cerebral hyperperfusion syndrome after
      carotid thromboendarterectomy.

PMID- 24276342
TI  - Patient page. Epilepsy and mood: update.

PMID- 24276344
TI  - The control of cellulose microfibril deposition in the cell wall of higher plants
      : I. Can directed membrane flow orient cellulose microfibrils? Indirect evidence
      from freeze-fractured plasma membranes of maize and pine seedlings.
AB  - In maize (Zea mays L.) and pine (Pinus taeda L.) seedlings, cellulose microfibril
      impressions are present on freeze-fractured plasma membranes. It has been
      proposed that impressions of newly synthesized microfibrils are a record of the
      movement of terminal synthesizing complexes through the plasma membrane (Mueller
      and Brown, 1980, J. Cell Biol. 84, 315-326). The association of terminal
      complexes with the ends of microfibril impressions or with the ends of
      microfibrils torn through the membrane indicates the orientation of microfibril
      tips. Unidirectionally-oriented microfibril tips (all pointing in the same
      direction) are associated with the organized deposition of parallel arrays of
      microfibrils. Multidirectionally-oriented microfibril tips were observed in a
      cell in which microfibril deposition was unusually disorganized. Microfibril
      patterns around pit fields are asymmetric and resemble flow patterns.
      Unidirectionally-oriented tears are associated with these microfibrils. Although
      microfibril orientations are deflected around pit fields, the main axis of
      microfibril orientation is maintained across the surface of the cell. The
      hypothesis is proposed that the interaction of a flowing plasma membrane with
      microfibril synthesizing complexes in the plane of the membrane may result in
      unidirectional deposition and asymmetric microfibril impressions around pit
      fields. 

PMID- 24276343
TI  - Barriers to human papillomavirus vaccination among US adolescents: a systematic
      review of the literature.
AB  - IMPORTANCE: Since licensure of the human papillomavirus (HPV) vaccine in 2006,
      HPV vaccine coverage among US adolescents has increased but remains low compared
      with other recommended vaccines. OBJECTIVE: To systematically review the
      literature on barriers to HPV vaccination among US adolescents to inform future
      efforts to increase HPV vaccine coverage. EVIDENCE REVIEW: We searched PubMed and
      previous review articles to identify original research articles describing
      barriers to HPV vaccine initiation and completion among US adolescents. Only
      articles reporting data collected in 2009 or later were included. Findings from
      55 relevant articles were summarized by target populations: health care
      professionals, parents, underserved and disadvantaged populations, and males.
      FINDINGS: Health care professionals cited financial concerns and parental
      attitudes and concerns as barriers to providing the HPV vaccine to patients.
      Parents often reported needing more information before vaccinating their
      children. Concerns about the vaccine's effect on sexual behavior, low perceived
      risk of HPV infection, social influences, irregular preventive care, and vaccine
      cost were also identified as potential barriers among parents. Some parents of
      sons reported not vaccinating their sons because of the perceived lack of direct
      benefit. Parents consistently cited health care professional recommendations as
      one of the most important factors in their decision to vaccinate their children.
      CONCLUSIONS AND RELEVANCE: Continued efforts are needed to ensure that health
      care professionals and parents understand the importance of vaccinating
      adolescents before they become sexually active. Health care professionals may
      benefit from guidance on communicating HPV recommendations to patients and
      parents. Further efforts are also needed to reduce missed opportunities for HPV
      vaccination when adolescents interface with the health care system. Efforts to
      increase uptake should take into account the specific needs of subgroups within
      the population. Efforts that address system-level barriers to vaccination may
      help to increase overall HPV vaccine uptake.

PMID- 24276345
TI  - The control of cellulose microfibril deposition in the cell wall of higher plants
      : II. Freeze-fracture microfibril patterns in maize seedling tissues following
      experimental alteration with colchicine and ethylene.
AB  - Cells of maize (Zea mays L.) seedling that are not fixed or cryoprotected contain
      the impressions of cellulose microfibrils on freeze-fractured plasma membranes.
      Impressions of the most recently deposited microfibrils have terminal complexes
      associated with them (see preceding paper). The orientations of microtubules in
      cytoplasmic fractures are parallel to the newest microfibrils observed on
      adjacent plasma membrane fractures. Small groups of microfibrils, distinguished
      from the next older layer by their new orientation, are sometimes observed
      directly adjacent and parallel to individual microtubules. Whereas microtubules
      are parallel to microfibril orientations which vary from transverse to
      occasionally longitudinal, microfilaments are parallel to the longitudinal cell
      axis. After colchicine treatment, cytoplasmic microtubules are absent, as are the
      bands of microfibrils that are observed on the membrane of control cells.
      Parallel orientations of microfibrils and normal pitfield outlines are often
      still observed after colchicine treatment. However, on some membranes,
      multidirectionally-oriented microfibril tips occur, associated with perturbations
      of microfibril orientation and rounded pit-field outlines. In ethylene-treated
      cells, some membranes have microfibril tips oriented in only one direction in new
      layers of longitudinal microfibrils. On other membranes, longitudinal bands of
      microfibril tips are oriented in opposing directions. We propose that after
      colchicine treatment, the patterns of microfibrils reflect an orientation
      mechanism which has been uncoupled from the influence of microtubules but which
      is still under some other form of cellular control. We propose that membrane flow
      could orient the lateral movement of synthesizing complexes in the membrane and
      that microtubules modulate this movement, apparently organizing the microfibrils
      into parallel bands in newly-forming wall layers. 

PMID- 24276346
TI  - Evidence for an intracellular sulfur cycle in cucumber leaves.
AB  - H2S emission from cucumber (Cucumis sativus L.) leaf discs supplied with L
      cysteine in the dark is inhibited 80-90% by aminooxyacetic acid (AOA), an
      inhibitor of pyridoxal-phosphate dependent enzymes. Exposure to L-cysteine in the
      light enhanced the emission of H2S in response to this sulfur source. Turning off
      the light reduced the emission of H2S to the rate observed in continuous dark;
      turning on the light enhanced the emission of H2S to the rate observed in
      continuous light. Therefore, in the light H2S emission in response to L-cysteine
      becomes a partially light-dependent process. Treatment with cyanazine, an
      inhibitor of photosynthetic electron transport, reduced H2S emission in the light
      to the rate observed in continuous dark, but did not affect H2S emission in the
      dark. In leaf discs pre-exposed to L-cysteine in the light, treatment with
      cyanazine+ AOA inhibited the emission of H2S in response to L-cysteine
      completely. Therefore, only part of the H2S emitted in response to this sulfur
      source is derived from a light-independent, but pyridoxal-phosphate-dependent
      process; the balance of the H2S emitted is derived from a light-dependent process
      that can be inhibited by cyanazine. When cucumber leaf discs were supplied with a
      pulse of L-[(35S)]cysteine, radioactively labeled H2S was emitted in two waves,
      one during the first hour of exposure to L-cysteine, and a second after 3-4 h;
      unlabeled H2S, however, was emitted continuously. The second wave of emission of
      labeled H2S was not observed in pulse-chase experiments in which sulfate or
      cyanazine were added to the treatment solution after 3 h of exposure to L
      cysteine, or when the lights was turned off. The labeling pattern of sulfur
      compounds inside cucumber cells supplied with a pulse of L-[(35)S]cysteine showed
      that the labeled H2S released from L-cysteine partially enters first the sulfite,
      then the sulfate pool of the cells. The radioactively labeled sulfate, however,
      is not incorporated into L-cysteine, but enters the H2S pool of the cells again.
      These observations are consistent with the idea of an intracellular sulfur cycle
      in plant cells. The L-cysteine taken up by the leaf discs seems to be
      desulfhydrated in a light-independent, but pyridoxal-phosphate-dependent process.
      The H2S synthesized this way may be partially released into the atmosphere; the
      other part of the H2S produced in response to L-cysteine may be oxidized to
      sulfite, then to sulfate, which is subsequently reduced via the light-depent
      sulfate assimilation pathway. In the presence of excess L-cysteine, synthesis of
      additional cysteine may be inhibited, and the sulfide moiety may be split off
      carrier bound sulfide to enter the H2S pool of the cells again. It is suggested
      that the function of this sulfur cycle may be regulation of the free cysteine
      pool. 

PMID- 24276347
TI  - The relationship of the charasome to chloride uptake in Chara corallina:
      physiological and histochemical investigations.
AB  - A possible role of the charasome in terms of chloride transport into Chara
      corallina Klein ex. Willd., em. R.D.W. is examined. The branches of Chara contain
      the most charasome material and are shown to be very effective in acquiring Cl(-)
      to support continued shoot growth. The early maturation of the branches, the
      rather large Cl(-) fluxes into these cells, and their ability of translocate Cl(
      ) to growing cells of the shoot indicate a special role of these branches in Cl(
      ) accumulation. The structure of the charasome, with its extensive periplasmic
      space, appears especially suited as a site for H(+)-Cl(-) cotransport (influx).
      We show, by histochemical assay, that the charasomes of mature cells contain
      ATPase activity; such activity is absent in growing charasomes of very young
      cells. ATPase activity is also associated with the plasmodesmata of C. corallina.
      Charasome ATPase activity and Cl(-) uptake are both inhibited by p
      chloromercuribenzenesulfonic acid (1 mM) or diethylstibestrol (40 MUM; 45 min).
      The anion transport inhibitor, 4,4-diisothiocyano-2,2-disulfonic acid stilbene (1
      mM) had no effect on Cl(-) transport and inhibited ATPase activity only when
      applied after chemical fixation of the cells. Results of an attempt to
      demonstrate the presence of Cl(-) within the cytoplasmic tubules of the
      charasome, using a silver precipitation technique, proved difficult to interpret
      because of a reaction between the silver and a cellular substance produced in the
      light. 

PMID- 24276348
TI  - Correlation between changes in photosynthetic activity and changes in total
      protoplast volume in leaf tissue from hygro-, meso- and xerophytes under osmotic
      stress.
AB  - Rates of photosynthesis of leaf slices from various hygro-, meso- and xerophytes
      were measured in the absence of stomatal control in various stages of osmotic
      dehydration. The external osmotic potential pi degrees  for a 50% inhibition of
      photosynthesis varied between 20 bar in some hygrophytes up to 50 bar in
      xerophytes. The response of photosynthetic enzymes to increased salt
      concentrations in the reaction medium was similar in leaf extracts from hygro-,
      meso- and xerophytes. The total protoplast volume in vacuum-infiltrated leaf
      discs from various plants was measured as the difference between (3)H2O-labeled
      space and [(14)C]sorbitol-labeled space. In all plants, the protoplast volume
      could be reduced to about 55% of the maximum volume of tissue in equilibrium with
      water, without decreasing photosynthesis. Reduction of the maximal protoplast
      volume below 55% decreased photosynthesis in all tissues to the same decreased
      photosynthesis in all tissues to the same degree. At 20% maximal volume,
      photosynthesis of all plants was completely inhibited. The differential decrease
      of protoplast volumes of various leaf tissues in response to changes in pi
      degrees  was mainly due to the different osmotic potential of the cell sap
      (pics). The relative contribution of sugars to the overall osmolarity of the cell
      sap was up to nineteen times higher in xerophytes than in hygrophytes. Short-term
      recovery of photosynthesis after hypertonic stress was good in xerophytes,
      incomplete in mesophytes and absent in hygrophytes. There was also a large
      discrepancy between the partial recovery of protoplast volumes and the complete
      absence of a recovery of photosynthesis in hygrophytes. 

PMID- 24276349
TI  - Hydroxylation of cinnamic acids and flavonoids during biosynthesis of
      anthocyanins in Petunia hybrida Hort.
AB  - The effect of hydroxylation genes on the hydroxylation of intermediates of
      flavonoid biosynthesis in Petunia hybrida is reported. In mutants homozygous
      recessive, for the gene An9, dihydroflavonols accumulate. The number of hydroxyl
      groups in the B-ring is determined by the hydroxylation genes Htl and Hfl. A
      similar effect of Htl and (probably) Hfl occurs in flavanone-accumulating
      mutants, homozygous recessive for the gene An3. Mutants dominant for Hfl probably
      accumulate a 5,7,3',4',5'-pentahydroxyflavanone. The mutant W43, homozygous
      recessive for the gene An5, is blocked in an early flavonoid biosynthesis step.
      It accumulates p-coumaric acid together with caffeic acid. The hydroxylation
      genes Htl and Hfl, however, are also homozygous recessive, which indicates that
      the hydroxylation of p-coumaric acid to caffeic acid or derivatives of these
      compounds is not controlled by Htl. The accumulation of caffeic acid was observed
      in all mutants investigated so far, regardless of which hydroxylation genes were
      dominant or recessive. We conclude that hydroxylations involved in anthocyanin
      biosynthesis occur at the C15 level. 

PMID- 24276350
TI  - Molecular weight distribution of cellulose in primary cell walls : Investigations
      with regenerating protoplasts, suspension cultured cells and mesophyll of
      tobacco.
AB  - The distribution pattern of the degree of polymerization (DP) of cellulose
      present in the cell walls of mesophyll- and suspension-cultured cells of tobacco
      was compared to that of newly synthesized (14)C-labeled cellulose from
      regenerating tobacco protoplasts and suspension-cultured cells. The cellulose was
      nitrated, and, after fractionation according to differences in solubility in
      acetone/water, the DP pattern of labeled or unlabeled cellulose nitrate was
      determined by viscosity measurements. A low (DP<500) and high DP-fraction
      (DP>2500) of cellulose were predominant in the cell walls of protoplasts,
      suspension - cultured cells, and mesophyll cells. The average DP of the high
      molecular weight fraction of cellulose in the cell walls of mesophyll was higher
      (DP~4,000) than in protoplasts or suspension - cultured cells (DP 2,500-3,000).
      In all cell walls tested, minor amounts of cellulose molecules with a broad
      spectrum of a medium DP were present. Pulse - chase experiments with either
      protoplasts or suspension -cultured cells showed that a large proportion of the
      low and medium DP-cellulose are a separate class of structural components of the
      cellulose network. The results are discussed in relation to the organization of
      cellulose in the primary cell wall. 

PMID- 24276352
TI  - A genetic basis for the origin of six different isolectins in hexaploid wheat.
AB  - Wheat (Triticum aestivum) germ agglutinin represents a complex mixture of
      multiple isolectin forms. Upon ion exchange chromatography at pH 3.8, three
      isolectins can be separated, each of which is composed of two identical subunits.
      At pH 5.0, however, three additional isolectins can be distinguished, which are
      built up of two different subunits (heteromeric lectins). Evidence is presented
      that these heterodimers are normal constituents of the wheat embryo cells.
      Analyses of the isolectin patterns in extracts from Triticum monococcum, Triticum
      turgidum dicoccum and Triticum aestivum, provide evidence that each genome,
      either in simple or complex (polyploid) genomes, directs the synthesis of a
      single lectin subunit species. In addition, a comparison of the isolectin pattern
      in these wheat species of increasing ploidy level, made it possible to determine
      unequivocally the genome by which the individual lectin subunits in polyploid
      species are coded for. The possible use of lectins in studies on the origin of
      individual genoms in polyploid species is discussed. 

PMID- 24276351
TI  - Transport and metabolism of [2(14)-C]abscisic acid in maize root.
AB  - The tips of intact maize (cv. LG 11) roots, maintained vertically, were
      pretreated with a droplet of buffer solution or a bead of anion exchange resin,
      both containing [2(14)-C]abscisic acid (ABA). A significant basipetal ABA
      movement was observed and two metabolites of ABA (possibly phaseic acid and
      dihydrophaseic acid) were found. ABA pretreatment enhanced the gravireaction of
      10 mm apical root segments kept both in the dark and in the light. The
      possibility that ABA could be one of the endogenous growth inhibitors produced or
      released by the cap cells is discussed. 

PMID- 24276353
TI  - Subunit exchange between lectins from different cereal species.
AB  - Lectins from Triticum monococcum, Secale cereale (rye), and Hordeum vulgare
      (barley) can exchange their subunits in vitro and thereby form (intergeneric)
      heteromeric lectins. An analysis of the isolectin pattern of a Triticale variety
      revealed that intergeneric heterodimers of wheat and rye lectin subunits are
      normal constituents of the embryo cells. It appears, therefore, that these
      different cereal lectins are structurally so closely related that their subunits
      can not distinguish between identical and nonidentical partners when they
      associate into dimers. 

PMID- 24276354
TI  - The induction of sensitivity to gibberellin in aleurone tissue of developing
      wheat grains : I. The effect of dehydration.
AB  - Aleurone layers from immature developing wheat grains (Triticum aestivum L. cvs.
      Sappo. and Champlein), though normally insensitive, can be made to produce alpha
      amylase in response to gibberellic acid by subjecting the grains to a period of
      enforced dehydration prior to introduction to the hormone. The change in
      sensitivity appears to depend upon the water content of the tissue, water levels
      of below approximately 25% being critical for the effect. Grain detachment or
      duration of drying apparently do not qualitatively influence the development of
      sensitivity to gibberellic acid. Enhanced sensitivity resulting from drying is
      not caused by changes in gibberellic acid uptake. A possible mechanism for the
      change in sensitivity of aleurone cells might be through structural alterations
      in cell membranes. 

PMID- 24276355
TI  - The induction of sensitivity to gibberellin in aleurone tissue of developing
      wheat grains : II. Evidence for temperature-dependent membrane transitions.
AB  - Aleurone tissue from undried immature developing wheat grains (Triticum aestivum
      L. cv. Sappo), normally insensitive to gibberellic acid, can be made to respond
      to the hormone by a series of temperature treatments. Incubation of the de
      embryoed grains at temperatures above 27 degrees  C for at least 8 h causes the
      tissue to become sensitive. Prolonged incubation at temperatures below 27 degrees
      C does not effect a change in sensitivity. In addition to the requirement for
      exposure to an elevated temperature for a period of several hours the tissue must
      also subsequently be subjected to a period at a lower temperature for just a few
      seconds for the response to be observed. Once sensitized, the tissue remains
      responsive to gibberellic acid for substantial periods of time. Exposure of the
      tissue to temperatures which induce sensitivity to gibberellic acid also results
      in an increased leakage of amino acids. It is suggested that the increase in
      sensitivity to gibberellin requires two separate processes to take place. One
      could be a homeoviscous adaptation of the cell membranes in response to elevated
      temperature, the other a subsequent, permanent change in conformation of membrane
      components. 

PMID- 24276356
TI  - Ammonium generation by nitrogen-starved cultures of Chlamydomonas reinhardii.
AB  - Ammonium (NH 4 (+) ) assimilation by Chlamydomonas reinhardii was inhibited when
      cultures were incubated with methionine sulphoximine (MSO). Methionine
      sulphoximine inhibited glutamine synthetase acitvity in vitro in extracts from
      wild-type (2192) and mutant (CC419) cultures. Mutant cultures were insensitive to
      MSO inhibition in vivo. Nitrogen-starved, wild-type cultures excreted ammonium
      when they were incubated with MSO in light or in darkness. Ammonium generation
      was stimulated by glutamine, inhibited by CO2 and stoichiometrically related to
      loss of protein. Notrogen replete cultures treated with MSO excreted ammonium in
      light but little was excreted in darkness. Ammonium excretion in darkness, in the
      presence of MSO, was enhanced by either a period of nitrogen deprivation or by
      the addition of acetate. Nitrogen deprivation also diminished the lag before
      ammonium excretion commenced. 

PMID- 24276357
TI  - Antidepressants and testicular cancer.
AB  - PURPOSE: Re-examine association of fluoxetine and paroxetine with risk of
      testicular cancer noted in drug screening, with 4 years more follow-up and
      expanded study of these and other antidepressant drugs. METHODS: In the Kaiser
      Permanente Medical Care Program in Northern California, 906 men with testicular
      cancer diagnosed August 1996-December 2010 were compared with 38,253 matched
      controls with race/ethnicity recorded regarding receipt of antidepressant drugs
      at least 2 years before diagnosis or control index date. Analyses emphasized
      duration of use and histological subgroups. RESULTS: With control for
      race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95 %
      confidence intervals (CI) for associations with testicular cancer were as
      follows: fluoxetine 1.22 (0.88-1.71), paroxetine 1.19 (0.78-1.83), and 1.21 (0.92
      1.58) for all serotonin reuptake inhibitors. There was no statistically
      significant association with risk of all testicular cancers or their histological
      subtypes for any individual drug or for tricyclics or all antidepressants
      combined except for citalopram with all testicular cancers 2.55 (1.43-4.52) and
      those of mixed histology 4.36 (1.50-12.68) and nefazodone with embryonal cancers
      9.79 (1.85-51.81). These could readily be chance findings in the context of the
      many analyses that were performed. Duration of use was not associated with risk
      of the drugs and drug groups with sufficient numbers of exposed cases for
      analysis. CONCLUSIONS: We found little evidence to support a testicular
      carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs, but
      a weakly positive association is not ruled out. The signals in prior screening
      may have been due to chance and/or uncontrolled confounding.

PMID- 24276358
TI  - Strategies used by an osteoporosis patient group to navigate for bone health care
      after a fracture.
AB  - OBJECTIVE: To examine experiences and behaviours with bone health management post
      fracture among members of a national osteoporosis (OP) patient group. METHODS: A
      qualitative study was conducted in English-speaking members of the group who had
      sustained a fragility fracture at 50+ years old and were not taking OP
      pharmacotherapy at the time of that fracture. Participants were recruited through
      an advertisement in the patient group newsletter and interviewed for ~1 h by
      telephone, responding to questions regarding visits to health care providers and
      their behaviours regarding bone health. We analysed the data following Giorgi's
      methodology. RESULTS: Twenty-eight eligible participants (26 females, two males;
      78% response rate) aged 51-89 years old completed an interview. More than half of
      our participants described effective consumer behaviours, including making
      requests of health care providers for referrals to bone specialists, bone mineral
      density tests, and prescription medication. CONCLUSION: Members of an OP patient
      group described effective consumer behaviours that could be incorporated as skill
      sets in post-fracture interventions to improve bone health.

PMID- 24276359
TI  - Outcomes of long retrograde intramedullary nailing for periprosthetic
      supracondylar femoral fractures following total knee arthroplasty.
AB  - BACKGROUND: The treatment of periprosthetic supracondylar femoral fractures
      following total knee arthroplasty (TKA) is challenging because of osteopenia and
      the limited bone available for distal fixation. The purpose of this study was to
      report the outcomes of periprosthetic supracondylar femoral fractures treated
      with long retrograde intramedullary nailing. METHODS: We conducted a
      retrospective review of 25 patients who were treated with a long retrograde
      intramedullary nail for periprosthetic supracondylar femoral fractures following
      TKA. Clinical evaluation included range of motion of knee, Knee Society Score
      (KSS), Western Ontario and McMaster Universities Arthritis (WOMAC) score, and
      radiologic evaluation including time to union, coronal and sagittal alignment of
      femoral component, lower limb alignment, and implant loosening. The mean duration
      of follow-up after the fracture repair was 39 months (range 12-47). RESULTS: All
      25 fractures were united with a mean time of 12 weeks (range 8-20). At the last
      follow-up, the mean knee flexion was 111 degrees  (range 60 degrees -130 degrees
      ), the mean KSS was 81.5 (range 50-100), and the mean WOMAC score was 30.2 (range
      5-55). Four (16%) of the 25 patients developed malalignment according to Rorabeck
      and Taylor criteria, but all patients had a knee flexion of more than 90 degrees
      . Coronal and sagittal alignments of femoral component and lower limb alignment
      did not differ significantly between before and after the fracture repair.
      Complications included the loosening or breakage of distal interlocking screws in
      three patients. No deep infection or prosthesis loosening was detected at the
      last follow-up. CONCLUSIONS: Surgical treatment of periprosthetic supracondylar
      femoral fractures following TKA with long retrograde intramedullary nailing
      resulted in high union rates and encouraging functional outcomes.

PMID- 24276360
TI  - Ten-year follow-up on Dutch orthopaedic blood management (DATA III survey).
AB  - INTRODUCTION: Hip and knee arthroplasties are frequently complicated by the need
      for allogeneic blood transfusions. This survey was conducted to assess the
      current use of perioperative blood-saving measures and to compare it with prior
      results. MATERIALS AND METHODS: All departments of orthopaedic surgery at Dutch
      hospitals were sent a follow-up survey on perioperative blood-saving measures,
      and data were compared to the results of two surveys conducted 5 and 10 years
      earlier. RESULTS: The response rate was 94 out of 108 departments (87%). Most
      departments used erythropoietin prior to hip and knee replacements at the expense
      of preoperative autologous blood donation. The use of intraoperative autologous
      retransfusion in revision hip (56 vs. 54%) as well as revision knee arthroplasty
      (26 vs. 24%), was virtually unchanged. Postoperative autologous retransfusion is
      still used by the majority of departments after both primary arthroplasty and
      revision of hip (58/53%) and knee (65/61%). CONCLUSIONS: Currently, just as in
      2007, the majority of Dutch orthopaedic departments uses erythropoietin,
      normothermia and postoperative autologous retransfusion with hip and knee
      arthroplasty. Intraoperative retransfusion is used mainly with hip revision
      arthroplasty. Other effective blood management modalities such as tranexamic acid
      have not been widely implemented.

PMID- 24276361
TI  - Diabetes mellitus increases the incidence of deep vein thrombosis after total
      knee arthroplasty.
AB  - INTRODUCTION: Many patients undergoing total knee arthroplasty (TKA) have
      diabetes mellitus, which may increase the risk of deep vein thrombosis (DVT)
      after TKA. We therefore assessed whether diabetes mellitus increased the
      incidence of DVT within 14 days after TKA. MATERIALS AND METHODS: The incidence
      of DVT within 14 days of surgery was compared in diabetic and non-diabetic
      patients undergoing TKA in our hospital between June 2011 and February 2013. The
      relationships between diabetes mellitus and DVT were analyzed. RESULTS: Of the
      358 enrolled patients, 70 (19.6%) had diabetes and 288 (80.4%) did not. DVT
      occurred within 14 days in 198 patients, 52 of 70 (74.3%) in the diabetes group
      and 146 of 288 (50.7%) in the non-diabetes group (p = 0.012). DVT of the
      contralateral leg was observed in 16 and 50 patients, respectively (p = 0.452).
      Logistic regression analysis showed that the risk of DVT was 2.71-fold higher in
      patients with than without diabetes mellitus (95% CI 1.183-6.212, p = 0.018).
      There were no significant differences in age, gender, hypertension, BMI, duration
      of surgery, intra-operative blood loss, and duration of tourniquet between the
      two groups. CONCLUSIONS: The incidence of DVT 14 days after TKA was significantly
      higher in patients with than without diabetes.

PMID- 24276362
TI  - Tibial component coverage based on bone mineral density of the cut tibial surface
      during unicompartmental knee arthroplasty: clinical relevance of the prevention
      of tibial component subsidence.
AB  - INTRODUCTION: An optimally implanted tibial component during unicompartmental
      knee arthroplasty would be flush with all edges of the cut tibial surface.
      However, this is often not possible, partly because the tibial component may not
      be an ideal shape or because the ideal component size may not be available. In
      such situations, surgeons need to decide between component overhang and underhang
      and as to which sites must be covered and which sites could be undercovered. The
      objectives of this study were to evaluate the bone mineral density of the cut
      surface of the proximal tibia around the cortical rim and to compare the bone
      mineral density according to the inclusion of the cortex and the site-specific
      matched evaluation. MATERIALS AND METHODS: One hundred and fifty consecutive
      patients (100 men and 50 women) were enrolled in this study. A quantitative
      computed tomography was used to determine the bone density of the cut tibial
      surface. Medial and lateral compartments were divided into anterior, middle, and
      posterior regions, and these three regions were further subdivided into two
      regions according to containment of cortex. The site-specific matched comparison
      (medial vs. lateral) of bone mineral density was performed. RESULTS: In medial
      sides, the mid-region, including the cortex, showed the highest bone mineral
      density in male and female patients. The posterior region showed the lowest bone
      mineral density in male patients, and the anterior and posterior regions showed
      the lowest bone mineral density in female patients. Regions including cortex
      showed higher bone mineral density than pure cancellous regions in medial sides.
      In lateral sides, posterior regions including cortex showed highest bone mineral
      density with statistical significance in both male and female patients. The
      anterior region showed the lowest bone mineral density in both male and female
      patients. CONCLUSION: The mid-region of the medial side and the posterior region
      of the lateral side are relatively safe without cortical coverage when the
      component is not flush with all edges of the tibia. Cortical coverage is strongly
      recommended for the prevention of subsidence of the tibial component in the
      posterior region of the medial side, and in the anterior region of the lateral
      side.

PMID- 24276363
TI  - Total knee arthroplasty after high tibial osteotomy: a registry-based case
      control study of 1,036 knees.
AB  - INTRODUCTION: Total knee arthroplasty (TKA) after high tibial osteotomy (HTO) is
      a technically demanding procedure, and concerns have been raised that previous
      HTO might compromise the outcome of TKA. The aims of the study were to assess the
      survivorship of TKA after HTO and to determine whether the survivorship is
      similar to that of primary TKA without previous HTO. MATERIALS AND METHODS: Using
      the Finnish Arthroplasty Register and the National Hospital Discharge Register,
      we extracted the data of 1,036 patients [mean age 64.3 years; followup 6.7 years
      (0-22)] who had undergone TKA after a previous HTO between 1987 and 2008. From
      this cohort, we calculated the Kaplan-Meier survivorship and compared the
      survivorship of these cases to that of 4,143 age- and gender-matched patients who
      had undergone primary TKAs without previous HTO. RESULTS: In the TKA after HTO
      group, we found Kaplan-Meier survivorship to be 95.3% at 5 years, 91.8% at 10
      years, and 88.4% at 15 years. Those survivorship values were lower than those of
      patients who had TKA without previous HTO (97.2, 94.5, and 90.6%, respectively)
      (hazard ratio 1.40; 95% confidence interval 1.09-1.81; p = 0.010). CONCLUSIONS:
      Previous studies have described technical difficulties during the TKA procedure
      after HTO, but they have found no adverse effects on the outcome. Our study
      supports previous research, and despite the slightly higher revision rate, TKA
      after HTO provides satisfactory results when compared to routine primary TKAs.

PMID- 24276364
TI  - Peroxidase-encapsulated cyclodextrin nanosponge immunoconjugates as a signal
      enhancement tool in optical and electrochemical assays.
AB  - Cyclodextrin nanosponges bearing carboxylate groups have been prepared by
      crosslinking beta-cyclodextrin with pyromellitic dianhydride to form a carboxylic
      acid terminated nanoporous material. The surface of the particles was covalently
      modified with an anti-IgG antibody and then loaded with horseradish peroxidase.
      The structures of unmodified and protein modified nanosponge particles were
      investigated by Raman spectroscopy and imaging methods. Confocal microscopy
      indicates that the antibody is located in the outside of the particle while HRP
      is encapsulated in the inner part. The possibility to use these modified
      nanosponges as a signal enhancement tool in enzyme-linked colorimetric and
      electrochemical assays was evaluated using a sandwich format comprising
      immobilised gliadin as an antigen, a target anti-gliadin antibody and an anti-IgG
      antibody conjugated to the enzyme-loaded nanosponge immunoconjugates. 

PMID- 24276365
TI  - Palmar and plantar melanomas differ for sex prevalence and tumor thickness but
      not for dermoscopic patterns.
AB  - The specific anatomy of the glabrous skin, characterized by marked orthokeratosis
      and the presence of furrows and ridges, results in peculiar dermoscopic patterns
      of acral melanocytic lesions. Most frequently, acral nevi are typified by a
      parallel furrow pattern and acral melanoma (AM) by a parallel ridge pattern
      (PRP). Although the dermoscopic patterns of AM have been extensively
      investigated, little attention has been paid to site-related differences between
      palmar and plantar AM. The current study aimed to compare patients'
      characteristics, melanoma thickness, and the morphologic variability of AM
      depending on the localization on palms or soles. Patients demographics and
      dermoscopic images of 118 AM, including 99 (83.9%) plantar and 19 (16.1%) palmar
      lesions (mean thickness, 2.1 mm), were extracted from the databases of seven
      pigmented skin lesion clinics and were evaluated for the presence of predefined
      criteria. Palmar melanomas were remarkably more frequent in women (male-to-female
      ratio, 1/3.8) and thinner than plantar melanomas (1.3 vs. 2.2 mm).
      Dermoscopically, no significant differences were found between plantar and palmar
      melanomas, with PRP scored in 64.6 and 68.4% of plantar and palmar lesions,
      respectively. Non-site-specific melanoma criteria were detected in 83.9% of
      lesions and, among melanomas not exhibiting a PRP, 95.1% showed at least one non
      site-specific melanoma criterion. In conclusion, plantar and palmar AMs show sex
      related and thickness-related differences, but do not differ with respect to
      their dermoscopic features. For cases lacking the PRP, non-site-specific melanoma
      criteria may be considered as helpful additional clues for the correct diagnosis.

PMID- 24276366
TI  - Environmental and genetic factors in the development of anticitrullinated protein
      antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological
      investigation in twins.
AB  - OBJECTIVE: To investigate the role of genetic and environmental factors in the
      development of anticitrullinated protein antibodies (ACPA) and ACPA-positive
      rheumatoid arthritis (RA) in a twin cohort. METHODS: A total of 12 590 twins were
      analysed for the presence of ACPAs (CCP2 ELISA), HLA-DRB1 shared epitope (SE)
      gene alleles, and exposure to smoking. Twins with established RA were identified
      in national public care registers. Antibody reactivities against citrullinated
      and native forms of alpha-enolase, vimentin, fibrinogen and type II collagen
      peptides were tested by ELISA in anti-CCP2-positive subjects and their cotwins.
      Structural equation models and ORs for the development of ACPA and ACPA-positive
      RA were computed for smokers and SE carriers. RESULTS: A total of 2.8% (350/12
      590) of the twins were ACPA positive, and 1.0% (124/12 590) had ACPA-positive RA.
      Most of the variability in the ACPA status was accounted for by non-shared
      environmental or stochastic factors (78%, 95% CI 55% to 100%) rather than shared
      environmental and genetic factors. Analysis of specific risk factors revealed an
      association between smoking and SE and the presence of ACPAs. Twins with ACPA
      positive RA were more frequently SE positive than twins with ACPAs without RA.
      Reactivities against multiple citrullinated peptides were present in most twins
      with ACPA-positive RA but in fewer twins with ACPAs without RA. CONCLUSIONS:
      Environment, lifestyle and stochastic factors may be more important than genetics
      in determining which individuals develop ACPAs. Genetic factors (particularly SE)
      may have a relatively larger role in determining which ACPA-positive individuals
      will ultimately develop arthritis.

PMID- 24276367
TI  - How dangerous are norovirus infections in patients with rheumatic diseases
      treated with biologics and DMARDs? Follow-up on a local outbreak and comparison
      with a control cohort.

PMID- 24276369
TI  - Electron density shape analysis of a family of through-space and through-bond
      interactions.
AB  - A family of styrene derivatives has been used to study the effects of through
      space and through-bond interactions on the local and global shapes of electron
      densities of complete molecules and a set of substituents on their central rings.
      Shape analysis methods which have been used extensively in the past for the study
      of molecular property-molecular shape correlations have shown that in these
      molecules a complementary role is played by the through-space and through-bond
      interactions. For each specific example, the dominance of either one of the two
      interactions can be identified and interpreted in terms of local shapes and the
      typical reactivities of the various substituents. Three levels of quantum
      chemical computational methods have been applied for these structures, including
      the B3LYP/cc-pVTZ level of density functional methodology, and the essential
      conclusions are the same for all three levels. The general approach is suggested
      as a tool for the identification of specific interaction types which are able to
      modify molecular electron densities. By separately influencing the through-space
      and through-bond components using polar groups and groups capable of conjugation,
      some fine-tuning of the overall effects becomes possible. The method described
      may contribute to an improved understanding and control of molecular properties
      involving complex interactions with a possible role in the emerging field of
      molecular design. 

PMID- 24276368
TI  - Degree of bone marrow oedema in sacroiliac joints of patients with axial
      spondyloarthritis is linked to gut inflammation and male sex: results from the
      GIANT cohort.
AB  - INTRODUCTION: Bone marrow oedema (BMO) of the sacroiliac joints (SIJs) is a
      hallmark of axial spondyloarthritis (SpA). However, the relationship between the
      extent of BMO and disease phenotype is poorly understood. OBJECTIVE: To assess
      the link between BMO of the SIJs and gut inflammation. We have also evaluated the
      correlation between BMO and established disease activity parameters. METHODS:
      Sixty-eight patients with axial SpA from the Gent Inflammatory Arthritis and
      spoNdylitis cohorT underwent ileocolonoscopy and MRI of the SIJs.
      Histopathological analysis and SPondyloArthritis Research Consortium of Canada
      (SPARCC) scores were performed. RESULTS: A significant higher SPARCC score
      (median (range)) was observed in axial SpA patients showing chronic gut
      inflammation (16.9 (3.8-68.3)) compared with axial SpA patients showing normal
      gut histology (9.8 (0.0-45.0); p<0.05). In a multiple linear regression model, we
      identified, besides chronic gut inflammation (effect size of 11.3, 95% CI (2.1 to
      20.4)), male sex (effect size of 10.5, 95% CI (3.3 to 17.8)) to be independently
      associated to the extent of BMO. There was a low to moderate correlation between
      the degree of BMO and C-reactive protein(r=0.39, p=0.002) and Ankylosing
      Spondylitis Disease Activity Score (r=0.35, p=0.007). CONCLUSIONS: Higher degrees
      of BMO were observed in patients showing chronic gut inflammation. These data
      solidify a link between mucosal inflammation and progressive disease in axial
      SpA.

PMID- 24276370
TI  - Immunolocalization of alpha-keratins and associated beta-proteins in lizard
      epidermis shows that acidic keratins mix with basic keratin-associated beta
      proteins.
AB  - The differentiation of the corneous layers of lizard epidermis has been analyzed
      by ultrastructural immunocytochemistry using specific antibodies against alpha
      keratins and keratin associated beta-proteins (KAbetaPs, formerly indicated as
      beta-keratins). Both beta-cells and alpha-cells of the corneous layer derive from
      the same germinal layer. An acidic type I alpha-keratin is present in basal and
      suprabasal layers, early differentiating clear, oberhautchen, and beta-cells.
      Type I keratin apparently disappears in differentiated beta- and alpha-layers of
      the mature corneous layers. Conversely, a basic type II alpha-keratin rich in
      glycine is absent or very scarce in basal and suprabasal layers and this keratin
      likely does not pair with type I keratin to form intermediate filaments but is
      weakly detected in the pre-corneous and corneous alpha-layer. Single and double
      labeling experiments show that in differentiating beta-cells, basic KAbetaPs are
      added and replace type-I keratin to form the hard beta-layer. Epidermal alpha
      keratins contain scarce cysteine (0.2-1.4 %) that instead represents 4-19 % of
      amino acids present in KAbetaPs. Possible chemical bonds formed between alpha
      keratins and KAbetaPs may derive from electrostatic interactions in addition to
      cross-linking through disulphide bonds. Both the high content in glycine of
      keratins and KAbetaPs may also contribute to increase the hydrophobicy of the
      beta- and alpha-layers and the resistance of the corneous layer. The increase of
      gly-rich KAbetaPs amount and the bonds to the framework of alpha-keratins give
      rise to the inflexible beta-layer while the cys-rich KAbetaPs produce a pliable
      alpha-layer.

PMID- 24276372
TI  - Removal of tracheal tube following unsuccessful resuscitation: a survey of
      current practice.

PMID- 24276371
TI  - Coordinated response of sulfate transport, cysteine biosynthesis, and glutathione
      mediated antioxidant defense in lentil (Lens culinaris Medik.) genotypes exposed
      to arsenic.
AB  - Response of sulfate transporters, thiol metabolism, and antioxidant defense
      system was studied in roots of two lentil (Lens culinaris Medik.) genotypes grown
      in arsenic (10, 25, and 40 MUM As(V))-supplemented nutrient solution, and
      significant changes compared to control (0 MUM As(V)) were observed mainly at 25
      and 40 MUM. In L 414, high glutathione (GSH) redox (0.8-0.9) was maintained with
      elevated thiol synthesis, powered by transcriptional up-regulation of LcSultr1;1
      and LcSultr1;2 sulfate transporters and significant induction of LcSAT1;1 and
      LcSAT1;2 (serine acetyltransferase), OAS-TL (O-acetylserine(thiol)-lyase), gamma
      ECS (gamma-glutamylcysteine synthetase), and PCS (phytochelatin synthase) genes
      predominantly within 12-24 h of As exposure at 25 MUM and within 6-12 h at 40
      MUM. This thiolic potency in L 414 roots was effectively complemented by up
      regulation of gene expressions and consequent enhanced activities of superoxide
      dismutase, ascorbate peroxidase (APX), dehydroascorbate reductase, glutathione
      reductase (GR), and glutathione-S-transferase (GST) isoforms at 25 and 40 MUMAs,
      efficiently scavenging excess reactive oxygen species to prevent onset of As
      induced oxidative stress and consequent inhibition of root growth in L 414. In
      contrast, down-regulation of vital sulfate-uptake transporters as well as entire
      thiol-metabolizing system and considerably low APX, GST, and GR expressions in
      DPL 59 not only resulted in reduced GSH redox but also led to over-accumulation
      of H2O2. This triggered membrane lipid peroxidations as the marks of As-induced
      oxidative damage. Results indicated coordinated response of thiol-metabolism and
      antioxidant defense in conferring As-tolerance in lentil, and GSH is the key
      point in this cascade.

PMID- 24276373
TI  - Anaesthesia for orphan disease: management of an infant with Silver-Russell
      syndrome.

PMID- 24276374
TI  - Anaesthesiological support in a cardiac electrophysiology laboratory.

PMID- 24276375
TI  - Analysis of transcription factor Stk40 expression and function during mouse pre
      implantation embryonic development.
AB  - Determining the molecular mechanisms in the regulation of early embryonic
      development is crucial for assisted reproductive technology clinical
      applications. Serine/threonine protein kinase 40 (Stk40) is a member of the
      serine/threonine kinase family. It is essential in diverse signaling pathways
      associated with a wide range of cellular activities, including proliferation,
      differentiation, survival and apoptosis. However, its involvement and molecular
      mechanisms in pre-implantation embryonic development have not been well-defined.
      In the present study, it was demonstrated that Stk40 was involved in the
      development of mouse pre-implantation embryos. Immunofluorescence and confocal
      microscopy analyses showed that Stk40 was equally expressed in the nuclei and
      cytoplasm during all stages of pre-implantation mouse embryos of imprinting
      control region mice. Reverse transcription-polymerase chain reaction showed a
      significantly higher transcription rate of Stk40 mRNA in the two-cell stage. The
      results demonstrated that Stk40 downregulation by microinjection of small
      interfering RNA into the mouse zygote markedly decreased the blastulation
      compared with that in the control (Stk40i-1 vs. control: 65.2% and 77.0%, P<0.05
      and Stk40i-2 vs. control: 49.8% and 70.1%, respectively, P<0.05). In addition,
      silencing of Stk40 significantly increased the transcription rate of
      reticulocalbin-2, whereas that of the homeobox protein, Cdx2, was decreased. In
      conclusion, the results suggested that Stk40 may be critical in the development
      of pre-implantation embryos.

PMID- 24276376
TI  - Targeting platelet thrombin receptor signaling to prevent thrombosis.
AB  - Platelets contribute fundamentally to ischemic heart disease, and antiplatelet
      therapy has been critical to reducing acute thrombotic complications of
      atherosclerotic disease. Thrombin, by acting on protease activated receptors
      (PAR), is one of the most potent platelet activators. PAR-1 antagonists may
      therefore provide more comprehensive antithrombotic effects. We review the
      pathophysiology of atherothrombosis, platelet activation by thrombin, the role of
      platelet protease activated receptors (PAR), and the clinical data supporting
      their use. 

PMID- 24276377
TI  - Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in
      Cancer.
AB  - It is well established that chronic inflammation underpins the development of a
      number of human cancers, with pro-inflammatory signaling within the tumor
      microenvironment contributing to tumor progression and metastasis. CXCL8 is an
      ELR+ pro-inflammatory CXC-chemokine which mediates its effects via signaling
      through two G protein-coupled receptors, CXCR1 and CXCR2. Elevated CXCL8-CXCR1/2
      signaling within the tumor microenvironment of numerous cancers is known to
      enhance tumor progression via activation of signaling pathways promoting
      proliferation, angiogenesis, migration, invasion and cell survival. This review
      provides an overview of established roles of CXCL8-CXCR1/2 signaling in cancer
      and subsequently, discusses the possible strategies of targeting CXCL8-CXCR1/2
      signaling in cancer, covering indirect strategies (e.g., anti-inflammatories,
      NFkappaB inhibitors) and direct CXCL8 or CXCR1/2 inhibition (e.g., neutralizing
      antibodies, small molecule receptor antagonists, pepducin inhibitors and siRNA
      strategies). Reports of pre-clinical cancer studies and clinical trials using
      CXCL8-CXCR1/2-targeting strategies for the treatment of inflammatory diseases
      will be discussed. The future translational opportunities for use of such agents
      in oncology will be discussed, with emphasis on exploitation in stratified
      populations. 

PMID- 24276378
TI  - The inhibition of stat5 by a Peptide aptamer ligand specific for the DNA binding
      domain prevents target gene transactivation and the growth of breast and prostate
      tumor cells.
AB  - The signal transducer and activator of transcription Stat5 is transiently
      activated by growth factor and cytokine signals in normal cells, but its
      persistent activation has been observed in a wide range of human tumors. Aberrant
      Stat5 activity was initially observed in leukemias, but subsequently also found
      in carcinomas. We investigated the importance of Stat5 in human tumor cell lines.
      shRNA mediated downregulation of Stat5 revealed the dependence of prostate and
      breast cancer cells on the expression of this transcription factor. We extended
      these inhibition studies and derived a peptide aptamer (PA) ligand, which
      directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid
      screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX)
      scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in
      bacteria, purified and introduced into tumor cells by protein transduction.
      Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a
      S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding
      ability of Stat5, suppressed Stat5 dependent transactivation and caused its
      intracellular degradation. Our experiments describe a peptide based inhibitor of
      Stat5 protein activity which can serve as a lead for the development of a
      clinically useful compound for cancer treatment. 

PMID- 24276380
TI  - Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor
      Blockade.
AB  - NMDA receptor (NMDA-R) is an important molecular entity governing a wide range of
      functions in the central nervous system. For example, the NMDA-R is involved in
      memory and cognition, and impairment of both (as in Alzheimer's Disease) is
      attributed to NMDA-mediated neurotoxicity. With greater understanding of the NMDA
      R structure, antagonists with varying degrees of binding-site and subtype
      selectivity have been developed and put into clinical use. Discovery of target
      specific Chinese herbs have also been made in parallel. This article provides an
      overview of the known active sites on the NMDA-R, followed by a discussion of the
      relevant herbs and their constituents. Experimental evidence supporting the
      inhibitory role of the herbal compounds on the NMDA-R is highlighted. For some of
      the compounds, potential research directions are also proposed to further
      elucidate the underlying mechanisms of the herbs. It is envisaged that future
      investigations based on the present data will allow more clinically relevant
      herbs to be identified. 

PMID- 24276382
TI  - Optimising two-stage independent culling selection in tree and animal breeding.
AB  - Theory is given for a simple practical method of predicting gain from two-stage
      independent culling, where stage 1 of selection is for individual performance and
      stage 2 is for either progeny performance only, or an index combining individual
      and progeny performance. Expected gain is determined as a direct function of
      heritabilities, genetic correlations, selection intensities and progeny-testing
      capacity. Results show the effect these parameters can have on proportions
      selected at each stage and, if multiple selection criteria are used, traits
      selected for first. Methods are discussed in the context of tree and animal
      breeding, with an example taken from forestry. 

PMID- 24276383
TI  - Methods for the production of multi-marker strains.
AB  - The production of a multi-marker strain given a series of strains each carrying a
      single marker will require a considerable investment in time and resources when
      based on a series of formal crosses. Such strains can be produced rapidly and
      with only minimal resources by recurrent cycles of random mating and selection,
      with selection based on the number of desired alleles carried. 

PMID- 24276384
TI  - The inheritance of node number and rate of node production in Brussels sprouts.
AB  - The total vegetative node number, rate of node production and number of sprouts
      over 13 mm diameter were recorded for 10 F1 Brussels sprout cultivars and 45
      progenies derived by intercrossing and selfing them. Significant differences,
      resulting from additive gene action, were found between the 10 cultivars and
      between their progenies for both characters. For total node number there was also
      evidence of dominant gene action. Total node number and rate of node production
      were closely correlated as were total node number and the number of harvested
      sprouts. The factors causing differences in rate of node production are indicated
      and the relationship of this character to other Brussels sprout yield components
      is outlined. 

PMID- 24276381
TI  - Characterization of Antimicrobial Peptides toward the Development of Novel
      Antibiotics.
AB  - Antimicrobial agents have eradicated many infectious diseases and significantly
      improved our living environment. However, abuse of antimicrobial agents has
      accelerated the emergence of multidrug-resistant microorganisms, and there is an
      urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted
      attention as a novel class of antimicrobial agents because AMPs efficiently kill
      a wide range of species, including bacteria, fungi, and viruses, via a novel
      mechanism of action. In addition, they are effective against pathogens that are
      resistant to almost all conventional antibiotics. AMPs have promising properties;
      they directly disrupt the functions of cellular membranes and nucleic acids, and
      the rate of appearance of AMP-resistant strains is very low. However, as
      pharmaceuticals, AMPs exhibit unfavorable properties, such as instability,
      hemolytic activity, high cost of production, salt sensitivity, and a broad
      spectrum of activity. Therefore, it is vital to improve these properties to
      develop novel AMP treatments. Here, we have reviewed the basic biochemical
      properties of AMPs and the recent strategies used to modulate these properties of
      AMPs to enhance their safety. 

PMID- 24276385
TI  - Genetic variation in the subunits of globulin-1 storage protein of French bean.
AB  - Charge and molecular weight heterogeneity of globulin-1 (G1) polypeptides of the
      bean, Phaseolus vulgaris L., were revealed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). Different bean cultivars were
      classified into three groups: 'Tendergreen', 'Sanilac', and 'Contender' on the
      basis of their protein subunit composition. Nine distinct major bands:
      alpha51,alpha49, alpha48.5,beta48(T), beta48(S), beta47, gamma45.5, gamma45(S),
      and gamma45(C), and two minor bands: gamma46(T) and gamma46(S) were found to
      account for the three profiles seen on one-dimensional SDS-PAGE. Two-dimensional
      analysis revealed these eleven protein bands to be composed of a minimum of
      fourteen distinct protein subunits. The 'Tendergreen' and 'Sanilac' types differ
      in their G1 polypeptide composition. The protein patterns of the 'Contender'
      types are intermediate, containing many protein subunits found in the patterns of
      the 'Tendergreen' and 'Sanilac' types suggesting a genetic and evolutionary
      relationship. 

PMID- 24276379
TI  - Personalizing colon cancer therapeutics: targeting old and new mechanisms of
      action.
AB  - The use of pharmaceuticals for colon cancer treatment has been increasingly
      personalized, in part due to the development of new molecular tools. In this
      review, we discuss the old and new colon cancer chemotherapeutics, and the
      parameters that have been shown to be predictive of efficacy and safety of these
      chemotherapeutics. In addition, we discuss how alternate pharmaceuticals have
      been developed in light of a potential lack of response or resistance to a
      particular chemotherapeutic. 

PMID- 24276386
TI  - Selection and characterization of ethionine-resistant alfalfa (Medicago sativa
      L.) cell lines.
AB  - Diploid alfalfa (HG2), capable of plant regeneration from tissue culture, was
      used to select variant cell lines resistant to growth inhibition due to ethionine
      (an analog of methionine). Approximately 10(7) suspension-cultured cells were
      mutagenized with methane sulfonic acid ethylester and then plated in solid media
      containing ethionine. Callus colonies formed on media with 0.02 mM ethionine. Of
      the 124 cell lines recovered, 91 regenerated plants. After six months growth on
      media without ethionine, 15 of 110 cell lines of callus grew significantly better
      than HG2 on 1 mM ethionine. Several ethionine-resistant callus cultures were also
      resistant to growth inhibition due to the addition of lysine + threonine to the
      media. High concentrations, relative to unselected HG2 callus, of methionine,
      cysteine, cystathionine, and glutathione were found in some, but not all,
      ethionine-resistant callus cultures. Cell line R32, which had a ca. tenfold
      increase in soluble methionine, had a 43% increase in total free amino acids and
      a 40% increase in amino acids in protein as compared to unselected HG2 callus.
      Relative amounts of each amino acid in protein were the same in both. 

PMID- 24276387
TI  - Variation for 2n pollen production in clones of Solanum phureja Juz. and Buk.
AB  - Frequency of unreduced pollen grains was estimated for five genotypes of Solanum
      phureja (2n=24) growing in three environments; (E1) cool (7.2-13.3 degrees C) and
      (E2) warm (12.2-17.2 degrees C) growth chambers and (E3) field conditions. Highly
      variable frequencies were found, with genotype, environment, and genotype x
      environment interaction as significant components of variance. The frequency of
      unreduced gametes for two additional genotypes was studied over time in two
      growth chamber environments (cool and warm). One genotype, characterized by
      mostly fused spindles at the second meiotic division, expressed a high frequency
      of big pollen (BP) in both environments, whereas the second, characterized by
      fused, parallel and tripolar second division spindless was found to increase in
      BP frequency over time in the cool chamber, but remained consistently low in the
      warm chamber. The identification of specific environmental components with
      general effect on the expression of un-reduced gametes is not possible because of
      the large genotype x environment interaction component of variance. A genetic
      hypothesis based on incomplete penetrance and variable expressivity of a dominant
      gene is presented as an alternative to the currently accepted theory of control
      of parallel spindles by a single recessive gene. 

PMID- 24276388
TI  - Worldwide patterns of genetic variation among four esterase loci in Barley
      (Hordeum vulgare L.).
AB  - Electrophoretic assays of 1506 accessions of domestic (Hordeum vulgare L.) and
      wild (H. spontaneum Koch.) barley, maintained in the USDA World Barley
      Collection, led to the following conclusions: (1) worldwide the four esterase
      loci, Est 1, Est 2, Est 3, and Est 4, have a minimum of 7, 12, 6, and 7 alleles,
      respectively; (2) little or no genetic differentation has developed between H.
      vulgare and H. spontaneum at these four esterase loci; (3) substantial genetic
      polymorphism and heterozygosity occur within many of the accessions despite the
      heavy inbreeding which results from the mating system of predominant self
      fertilization and from genetic drift associated with maintenance in small
      populations; (4) patterns of geographical distribution of alleles at these four
      loci are not at random over both small and large geographical areas, including
      differences on a continental scale; (5) four among 16 four-locus combinations of
      alleles are found in excess and all other combinations occur in deficiency on a
      worldwide basis. 

PMID- 24276389
TI  - Amino acids in anthers of Milo and in cytoplasmic genetic male sterile sorghums
      (Sorghum bicolor L. Moench) of Indian origin.
AB  - Amino acid composition of proteins from anthers of milo and Indian origin male
      steriles were determined. Comparison of amino acid between A and B lines showed
      lower contents of histidine, threonine, glutamic acid, glycine, leucine and
      phenylalanine and higher contents of alanine, serine, proline and tyrosine in
      line A compared to line B. Alanine content in anthers of A lines was more than
      two fold higher than that in the anthers from B lines. Marked differences in
      amino acid composition of anthers of A and B lines are suggestive of their
      involvement in male sterility. Cytoplasmic male steriles of Indian origin M35-1A
      and M31-2A showed greater similarity but differed from milo, VZM2A and B. 

PMID- 24276390
TI  - The genome specific grain proteins and the phylogenetic interrelation between
      Triticum L., Elytrigia Desf., Elymus L. and Agropyron Gaertn.
AB  - Immunochemical protein studies show that nongliadins of the ethanol-soluble
      fraction (EF) provide the best biochemical information on genome interrelations
      in cereals. After electrophoresis (pH 3.2) these genome specific proteins are
      shown to fall within the category of alpha-prolamines and albumins where
      inhibitors against alpha-amylases are to be found. Although these genome specific
      proteins of the EF exhibit identical serological properties, they may differ in
      electrophoretic mobility. They may very well be controlled by different
      chromosomes within a certain, characteristic genome. Electrophoretic analyses
      will thus likely reveal interrelations between individual chromosomes or even
      chromosome segments while the precipitation spectrum of the EF will function as a
      marker of the whole genomes or at least of the major part of their genetic
      material. This advantage of the immunological technique has been explored in a
      study of the phylogenetic relations between different genomes belonging to
      Triticum L., Elytrigia Desf., Elymus L. and Agropyron Gaertn. Serological markers
      for the main genomes of Triticum were checked against species and genomes of the
      other three genera.More than 80 species belonging to these three genera were
      proved to be immunologically distinctive from the wheat genomes. Antigens
      produced against diploid Elytrigia species were not only checked with other
      species belonging to Elytrigia but also to Elymus and Agropyron. This inventory
      of interrelationships confirmed previous knowledge and also added some new
      information on the phylogeny of the polyploid representatives of Elytrigia and
      Elymus. 

PMID- 24276391
TI  - Genotype-environment interaction effects on reproductive performance in Tribolium
      castaneum.
AB  - Three lines of Tribolium castaneum were raised totally on a yeast-free or yeast
      supplemented diet, or raised to pupation on a yeast-free diet and then on a yeast
      supplemented diet, and vice versa, to study the effects of genotype x environment
      interaction and diet changes after pupation on reproduction.Feeding the yeast
      supplemented diet generally resulted in earlier sexual maturation, heavier adult
      weights and higher egg production. The diets had no effects on larval viability.
      Changes in diet after pupation had no effects on age at sexual maturity or adult
      weight. Egg production was determined largely by the environment just prior to
      and during egg laying. However, egg production on the yeast-free diet was
      influenced by the pre-pupation diet.There was significant line x environment
      interaction effects on age at sexual maturity, mature egg production and adult
      weight (P<0.01). There was also a sire x environment effect on egg production
      (P<0.05). 

PMID- 24276393
TI  - A review of bullying prevention and intervention in South Korean schools: an
      application of the social-ecological framework.
AB  - School bullying is a serious social problem that results in potentially severe
      and long lasting consequences for youth, parents, teachers, and school officials.
      Commensurate with the serious nature and outcomes of bullying, there has been a
      number of bullying prevention and intervention programs and measures in schools.
      The current review provides a synthesis and evaluation of the existing research
      on bullying prevention and intervention strategies in South Korean schools, set
      within Bronfenbrenner's social-ecological contexts, including the micro- (i.e.,
      family, peer, school), meso- (i.e., family-school), and macro- (i.e., religion,
      policies) systems. We also discuss the strengths and limitations of the research
      reviewed and provide directions for future research focusing on major empirical
      gaps in the literature on bullying prevention and intervention strategies in
      South Korea. 

PMID- 24276392
TI  - Recognition of pain as another deficit in young males with high callous
      unemotional traits.
AB  - Prior research on callous-unemotional (CU) traits supports a deficit in
      recognizing fear in faces and body postures. Difficulties recognising others'
      emotions may impair the typical behavioural inhibition for violent behaviour.
      However, recent research has begun to examine other distress cues such as pain.
      The present study examined emotion recognition skills, including pain, of school
      excluded boys aged 11-16 years (N = 50). Using dynamic faces and body poses, we
      examined the relation between emotion recognition and CU traits using the youth
      psychopathic traits inventory (YPI) and the inventory of CU traits. Violent
      delinquency was covaried in regression analyses. Although fearful facial and
      fearful bodily expressions were unrelated to CU traits, recognition of dynamic
      pain facial expressions was negatively related to CU traits using the YPI. The
      failure to replicate a fear and sad deficit are discussed in relation to previous
      research. Also, findings are discussed in support of a general empathy deficit
      for distress cues which may underlie the problem behaviour of young males with CU
      traits.

PMID- 24276395
TI  - Towards biocompatible nano/microscale machines: self-propelled catalytic
      nanomotors not exhibiting acute toxicity.
AB  - Recent advances in nanotechnology have led to the evolution of self-propelled,
      artificial nano/microjet motors. These intelligent devices are considered to be
      the next generation self-powered drug delivery system in the field of biomedical
      applications. While many studies have strived to further improve the various
      properties of these devices such as their efficiency, performance and power,
      little attention has been paid to the actual biocompatibility of nanojets in
      vivo. In this paper, we will present for the first time the investigation of the
      toxicity effects of nanojets on the viability of human lung epithelial cells
      (A549 cells). From the 24 h and 48 h post-exposure studies, it is clearly shown
      that the nanojets we used in our work has negligible influence on the cell
      viability across all the concentrations tested. As such, the toxicity profile of
      our nanojets have been shown to be neither dose- nor time-dependent. This is
      strongly indicative of the benign nature of our nanojets, which is of paramount
      significance as it is the first step towards the applications of nano/micromotors
      in real-world practical medical devices. 

PMID- 24276394
TI  - Sleep-wake patterns reported by parents in hyperactive children diagnosed
      according to ICD-10, as compared to paired controls.
AB  - This study aimed primarily to compare the parent-reported sleep of children with
      ICD-10 hyperkinetic disorder (HKD) versus community children. Thirty children
      aged 5-13 years (83.3% boys) diagnosed with HKD by their child and adolescent
      psychiatrists took part in this study, plus 30 community children, matched for
      sex, age, and school year. Compared to the controls, the HKD children showed
      significantly later bedtimes, stronger bedtime resistance, longer sleep latency,
      shorter sleep; more frequent behaviors and symptoms concerning falling asleep
      into parents bed, needing something special to initiate sleep, nightmares, sleep
      talking, sleep bruxism, fear from darkness, bedwetting, and, most notably, loud
      snoring (26.7%); they also tended to show higher daytime somnolence. Attention
      deficit/hyperactivity disorder (ADHD)/HKD children may thus have more sleep
      related problems than typically developing children. Alternatively, our results
      may reflect misdiagnoses; thus, special attention should be directed to
      comorbidity and differential diagnosis issues between sleep disturbances and
      ADHD/HKD.

PMID- 24276396
TI  - Antinutritional effects and ecological significance of dietary condensed tannins
      may not be due to binding and inhibiting digestive enzymes.
AB  - The digestive enzymes alkaline phosphatase and 5'-nucleotide phosphodiesterase,
      solubilized from bovine intestinal mucosa and purified to homogeneity, were found
      to be strongly inhibited in vitro by condensed tannins (proanthocyanidins)
      purified from sorghum seeds and from quebracho. Tannin inhibition was prevented
      and reversed by the detergent Triton X-100 (protein-binding agent), by soluble
      polyvinylpyrrolidone (tannin-binding agent), or by phosphatidylcholine (membrane
      component). When tested as a crude particulate membrane fraction more
      characteristic of their in vivo condition, both enzymes were inhibited much less
      than either purified enzyme at the same tannin concentration. Because the enzymes
      appear to be relatively insensitive to inhibition by tannin in conditions which
      mimic in vivo conditions, and because the proportion of the dietary tannin which
      is available to interact with these enzymes in the digestive tract is likely to
      be rather small, we suggest that the antinutritional effects and ecological
      significance of dietary tannins are not due to tannin inhibition of these or
      other digestive enzymes by direct binding to them. 

PMID- 24276397
TI  - Castanospermine-a plant growth regulator.
AB  - Castanospermine, 1,6,7,8-tetrahydroxyoctahydroindolizine, has been shown to be a
      potent dicot phytotoxin. The effective concentration to inhibit root length
      elongation of dicot roots by 50% is 300 ppb, while the effective concentration
      against monocot roots is 200 ppm, i.e., 10(3) times less effective. In contrast
      swainsonine, 1,2,8-trihydroxyoctahydroindolizidine, is ineffective as an
      inhibitor of root length elongation. 

PMID- 24276398
TI  - Host egg kairomones essential for egg-larval parasitoid,Ascogaster reticulatus
      watanabe (Hymenoptera: Braconidae) : I. Internal and external kairomones.
AB  - An artificial egg with a Parafilm membrane was devised for the oviposition
      ofAscogaster reticulatus Watanabe (Hymenoptera: Braconidae), an egg-larval
      parasitoid of the smaller tea tortrix,Adoxophyes sp. (Lepidoptera: Tortricidae).
      Both external and internal kairomones were essential. The external kairomone,
      needed for host location and acceptance, was extracted with 70% ethanol, and the
      internal kairomone, needed for oviposition, was extracted with water. Female
      parasitoids responded to the external kairomone and oviposited through the
      membrane into the artificial egg when the supernatant of host egg-mass homogenate
      was inside, whereas they did not when water or saline solutions were inside. Thus
      an internal kairomone is responsible for the oviposition in the host egg. The
      internal kairomone apparently was not specific for the host egg mass because
      oviposition activity was found not only in egg, larval, and pupal stages of the
      host, but also in larvae of other species of Lepidoptera and Coleoptera. 

PMID- 24276399
TI  - Identification of tobacco hornworm antibiosis factor from cuticulae of repandae
      section ofNicotiana species.
AB  - Cuticular components of the green leaves of the Repandae section of theNicotiana
      species contain compounds that have been shown to be toxic to larvae of the
      tobacco hornworm larvae,Manduca sexta. The surface constituents of leaves of
      greenhouse-grownN. repanda, N. stocktonii, andN. nesophila were extracted with
      methylene chloride in order to isolate the active compounds. Solvent partitioning
      and gel chromatography was used to isolate a series of hydroxyacylnornicotines
      (HOAcylNN). The major component was identified asN'-(3-hydroxy-12
      methyltridecanoyl)nornicotine. A number of minor 3-hydroxyacylnornicotines, with
      the acyl group containing C13-C15, were also identified. The HOAcylNN mixture in
      ethanol was topically applied to first-instar tobacco hornworm larvae at rates of
      10, 50, 100, and 200 MUg. Mortalities after 48 hr were 33, 44, 78, and 100%
      respectively. 

PMID- 24276400
TI  - Mating stimulant of the pine weevilHylobius abietis (L.).
AB  - Factors eliciting copulatory behavior in mature maleHylobius abietis were studied
      in the laboratory. Dead female weevils were sexually attractive, while dead
      mature males and pentane-extracted female weevils were not. The sexual
      attractiveness of dead females declined with time after death. Pentane extracts
      of whole female weevils or of the anterior or posterior parts of their bodies
      elicited a copulatory response when applied to decoys. In contrast, extracts of
      hindgut or frass were inactive. Juvenile males were sexually attractive for about
      four weeks, after which their attractiveness gradually declined. The results
      indicate that the mating stimulant is present on the body surface of female and
      juvenile male weevils, and it can be extracted with pentane. 

PMID- 24276401
TI  - Camphor from juvenile white spruce as an antifeedant for snowshoe hares.
AB  - One theory in plant antiherbivore defense predicts that slow growing late
      succession plants like white spruce (Picea glauca) make large investments in
      antiherbivore defenses. Juvenile stages of white spruce in the Yukon, Canada, are
      rarely browsed by snowshoe hares (Lepus americanus), an abundant herbivore, but
      mature spruce is a highly preferred food. The hexane-soluble fractions of the
      methanol extracts from juvenile and mature white spruce contain camphor and bomyl
      acetate. There is four times as much camphor in juvenile spruce as in mature
      spruce from GC analysis. Plant extracts were added to rabbit chow. Pairs of
      extracts were offered to hares in choice tests. These tests demonstrated that
      camphor in the juvenile spruce extracts deterred feeding. Bornyl acetate did not
      have a clear antifeeding effect. 

PMID- 24276402
TI  - Artificial defloration and furanocoumarin induction inPastinaca sativa
      (Umbelliferae).
AB  - Damage simulating herbivory was tested as an inducer of furanocoumarins in the
      floral parts of the wild parsnip,Pastinaca sativa (Umbelliferae). In one
      experiment, primary umbels ofP. sativa were partially deflorated over the course
      of nine days, and higher-order umbels as well as the remaining primary umbel
      floral parts were sampled. Total furanocoumarin concentration was not
      significantly affected by defloration, but one furanocoumarin, isopimpinellin,
      increased in one floral stage of the secondary umbel in damaged plants. In a
      second experiment, primary umbels were completely deflorated and the higher-order
      umbels allowed to set seed. No significant effect of defloration on
      furanocoumarin content was found in the seeds of the higher-order umbels. 

PMID- 24276403
TI  - Behavioral responses of western corn rootworm larvae to volatile semiochemicals
      from corn seedlings.
AB  - Corn seedling volatiles collected cryogenically are highly attractive to western
      corn rootworm larvae,Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), in a laboratory bioassay. Carbon dioxide is known as an
      attractant for western corn rootworm larvae, and the amount of carbon dioxide in
      the cryogenic collections was measured with an infrared gas analyzer. In a choice
      test between a source containing carbon dioxide alone and a source containing
      corn seedling volatiles with an equal amount of carbon dioxide (verified by
      infrared gas analysis), western corn rootworm larvae chose the corn volatile
      source significantly more often than the side with carbon dioxide alone. This
      indicates that carbon dioxide is only one of the volatiles from corn seedlings
      that is behaviorally important and that other compounds of behavioral importance
      are present as well. 

PMID- 24276404
TI  - A family of cationic oxime-based hexametallic manganese(III) single-molecule
      magnets.
AB  - Three novel cationic hexametallic Mn(III) compounds of formulae [Mn6(MU3-O)2(H2N
      sao)6(py)6(EtOH)2](ClO4)2.4EtOH (1), [Mn6(MU3-O)2(H2N
      sao)6(tpy)6(H2O)2](ClO4)2.2tpy.4H2O.2EtOH (2) and [Mn6(MU3-O)2(H2N
      sao)6(Him)6(EtOH)2](ClO4)2.6EtOH (3) [H2N-saoH2 = salicylamidoxime, py =
      pyridine, tpy = 4-tert-butylpyridine and Him = imidazole] have been synthesised
      and magnetostructurally characterised. These [Mn6](2+) complexes are new members
      of the oxime-based family of neutral [Mn6] single-molecule magnets (SMMs) in
      which the previously terminally bonded carboxylates, phosphinates, halides or ROH
      molecules on the outwardly facing triangular faces have been replaced with
      pyridine (1), 4-tert-butylpyridine (2) and imidazole (3) molecules generating a
      new series of salts based on Mn6 complexes. These results suggest that the
      cationic [Mn6](2+) species could be used as suitable building blocks for
      preparing new materials with different functionalities.

PMID- 24276405
TI  - Integrins and their ligands are expressed in non-small cell lung cancer but not
      correlated with parameters of disease progression.
AB  - The aim of this study was to investigate the expression of integrins, their
      ligands, and integrin signaling-related molecules in a cohort of human primary
      non-small cell lung cancers (NSCLC). Formalin-fixed and paraffin-embedded tissue
      samples from 215 NSCLC were immunohistochemically stained using antibodies
      directed against alphavbeta3, alphavbeta5, alphavbeta6, alphavbeta8, alphav,
      osteopontin, fibronectin, vitronectin, epidermal growth factor (EGFR), vascular
      endothelial growth factor receptor (VEGFR), and Ki67. Immunostaining of tumor,
      stroma, and endothelial cells was evaluated separately by quantity and intensity
      (tumor cells) or intensity (stroma and endothelial cells) expressed in an
      immunoreactivity score. We studied correlations between the staining patterns of
      the different markers and of marker expression with clinicopathological data and
      patient survival. In the majority of NSCLC, each marker was expressed in at least
      one tumor component. As expected, alphav and alphav integrin heterodimers were
      significantly co-expressed, as were integrins and EGFR. Vitronectin was expressed
      significantly more often in smaller (T-category) and in well-differentiated
      tumors; Ki67 index was higher in larger (T-category) and in poorly differentiated
      tumors. No significant correlation was found between any marker expression and
      gender, venous invasion, lymph vessel invasion, lymph node metastasis, or
      survival. Although integrin expression does not seem to be associated with
      indicators of progression of NSCLC, the expression of alphavbeta3 in 89 % and
      alphavbeta5 in 100 % of NSCLC is novel and merits to be further investigated.

PMID- 24276406
TI  - HPV typing of high-grade dysplasia (CIN III) in cone biopsies of 38 HPV
      vaccinated women.
AB  - HPV-vaccinated women develop CIN III very rarely. We have identified a study
      group of 38 such patients and showed that a specific HPV genotype prevalence in
      those cases equals the prevalence of HPV genotypes in CIN III present in the
      general Czech population. In all cases, CIN III was diagnosed within 3 years
      after having completed the HPV vaccination. We conclude that dysplasia was
      present before the vaccination in those women. A history of abnormal pre
      vaccination PAP smear result (present in 78 % of women in the study group) and
      age of over 17 by the time of vaccination completion (97 % of women in the study
      group) are identified as probable factors increasing the risk of CIN III
      development after HPV vaccination.

PMID- 24276407
TI  - ALDH3A1 is overexpressed in a subset of hepatocellular carcinoma characterised by
      activation of the Wnt/beta-catenin pathway.
AB  - Aldehyde dehydrogenase isoforms, ALDH1A1 and ALDH3A1, are associated with poor
      clinical outcome and resistance to chemotherapy in a wide variety of human
      malignancies. So far, their expression and prognostic significance in
      hepatocellular carcinoma (HCC) remains unknown. The aim of our study was to
      investigate their expression in HCC, and to correlate this to clinical,
      pathological and molecular features. ALDH1A1 and ALDH3A1 expression was first
      evaluated by microarray analysis in a series of 60 HCCs and five tumour-free
      liver tissue samples. Our findings related to ALDH3A1 were further validated by
      immunohistochemistry in a series of 81 HCCs and 23 hepatocellular adenomas (HCA).
      Microarray analysis showed no difference in ALDH1A1 expression between HCCs and
      tumour-free liver tissue. In contrast, ALDH3A1 was strongly upregulated in a
      subset of HCCs characterised by activation of the Wnt/beta-catenin pathway and
      CTNNB1 mutations. Using immunohistochemistry, we confirmed that high ALDH3A1
      expression is associated with nuclear staining for beta-catenin and strong
      homogeneous staining for glutamine synthetase, two classical Wnt/beta-catenin
      pathway activation markers. Consistent with this finding, in tumour-free liver
      tissue, ALDH3A1 expression was observed in centrilobular hepatocytes, in which
      the Wnt/beta-catenin pathway is known to be physiologically activated. We also
      observed higher ALDH3A1 expression in CTNNB1-mutated HCA when compared with other
      subtypes. No correlation between ALDH3A1 expression and patient survival or
      tumour recurrence was observed.In conclusion, ALDH3A1 is a marker of activation
      of the Wnt/beta-catenin pathway in HCC, HCA and tumour-free liver tissue. Further
      studies may help to elucidate the potential role of ALDH3A1 in HCC development
      and resistance to chemotherapy. 

PMID- 24276408
TI  - omega-3 polyunsaturated fatty acids inhibit the proliferation of the lung
      adenocarcinoma cell line A549 in vitro.
AB  - omega-3 polyunsaturated fatty acids (n-3 PUFA), in particular the marine-derived
      forms eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been
      demonstrated to affect cancer cell replication, the cell cycle and cell death.
      Epidemiological studies have also suggested diets rich in n-3 PUFA were inversely
      correlated with the development of cancer. In the present study, we explored the
      effects of DHA and EPA on the proliferation activity and apoptosis of the human
      lung adenocarcinoma cell line A549. A methyl thiazolyl tetrazolium (MTT) assay
      was used to detect cell proliferation, apoptosis was detected by flow cytometry
      and morphological analysis was determined by fluorescence microscopy and
      transmission electron microscopy. A549 cells were treated with different doses of
      DHA (40, 45, 50 and 55 ug/ml) or EPA (45, 50, 55 and 60 ug/ml) for 24, 48 and 72
      h. The results demonstrated that DHA and EPA significantly suppressed the
      proliferation of A549 cells and induced apoptosis of A549 cells in a dose- and
      time-dependent manner. The apoptotic phenomenon was also confirmed by
      fluorescence microscopy and transmission electron microscopy. Furthermore,
      compared with the control, the formation of autophagosomes was clearly enhanced
      in DHA- or EPA-treated cells. In conclusion, DHA and EPA inhibited the
      proliferation of A549 cells and induced cell apoptosis and autophagy, which may
      provide new safe and effective options for the treatment of lung cancer in the
      future.

PMID- 24276409
TI  - Expression of metallothionein of freshwater crab (Sinopotamon henanense) in
      Escherichia coli enhances tolerance and accumulation of zinc, copper and cadmium.
AB  - Metallothioneins (MTs) are ubiquitous metal-binding, cysteine-rich, small
      proteins and play a major role in metal homeostasis and/or detoxification in all
      organisms. In a previous study, a novel full length MT gene was isolated from the
      freshwater crab (Sinopotamon henanense), a species widely distributed in Shanxi
      and Henan Provinces, China. In this report, the gene for the crab MT was inserted
      into a PET-28a-6His-SUMO vector and recombinant soluble MT was over-expressed as
      fusions with SUMO in Escherichia coli. The recombinant fusion protein was
      purified by affinity chromatography and its biochemical properties were analyzed.
      In addition, on the basis of constructing SUMO-MT, two mutants, namely SUMO-MTt1
      and SUMO-MTt2, were constructed to change the primary structure of SUMO-MT using
      site-directed mutagenesis techniques with the amino acid substitutions D3C and
      S37C in order to increase metal-binding capacity of MT. E. coli cells expressing
      SUMO-MT and these single-mutant proteins exhibited enhanced metal tolerance and
      higher accumulation of metal ions than control cells. The results showed that the
      bioaccumulation and tolerance of Zn(2+), Cu(2+) and Cd(2+) in these strains
      followed the decreasing order of SUMO-MTt1 > SUMO-MTt2 > SUMO-MT. E. coli cells
      have low tolerance and high accumulation towards cadmium compared to zinc and
      copper. These results show that the MT of S. henanense could enhance tolerance
      and accumulation of metal ions. Moreover, we were able to create a novel protein
      based on the crab MT to bind metal ions at high density and with high affinity.
      Therefore, SUMO-MT and its mutants can provide potential candidates for heavy
      metal bioremediation. This study could help further elucidate the mechanism of
      how the crab detoxifies heavy metals and provide a scientific basis for
      environment bioremediation of heavy metal pollution using the over-expression of
      the crab MT and mutant proteins. 

PMID- 24276410
TI  - Biochemical, histological and ultrastructural alterations of the alimentary
      system in the freshwater crab Sinopotamon henanense subchronically exposed to
      cadmium.
AB  - Cadmium (Cd) is one of the toxic metals in the aquatic environment. We
      investigated the effects of Cd on the digestive enzymes, antioxidant enzymes,
      malondialdehyde (MDA) content and morphology of the hepatopancreas and intestine
      in the freshwater crab Sinopotamon henanense. Crabs were exposed to sublethal Cd
      concentrations of 0, 0.725, 1.450 and 2.900 mg/L for 21 days. After Cd exposure,
      the activities of maltase, amylase and trypsin of two tissues were lower than the
      control. The activities of superoxide dismutase, catalase and glutathione
      peroxidase in the hepatopancreas and intestine were decreased, and the MDA
      concentration increased in all of the treated groups, over the experimental
      period. The results of light and transmission electron microscopy showed that
      2.900 mg/L of Cd exposure caused profound morphological damages in the
      hepatopancreas and midgut. After exposure, histological abnormalities of two
      tissues were discovered, including cellular swelling and necrosis. Additionally,
      alterations in microvilli, nucleus, mitochondria, rough endoplasmic reticulum as
      well as Golgi complex in epithelial cells of two tissues were observed. This may
      be due to antioxidant enzymes activities that were reduced by Cd in the
      alimentary system of the crabs, and led to membrane lipid peroxidation. The
      membrane structure was destroyed, and caused further tissue damage, which likely
      made the alimentary system unable to secrete digestive enzymes, leading to
      further reduction of digestive enzymes. 

PMID- 24276411
TI  - Gastroesophageal reflux in infants: more than just a pHenomenon.
AB  - IMPORTANCE: Rarely have the best methods of diagnosis or the treatment of a
      disease engendered more controversy than gastroesophageal reflux (GER), a highly
      prevalent condition in infants. OBJECTIVE: To discuss the latest controversies in
      the diagnosis and treatment of GER in infants. EVIDENCE REVIEW: All articles
      related to the diagnosis and treatment of GER were reviewed and, whenever
      possible, literature about infants was weighted with greater importance than
      literature about older children and adults. FINDINGS: Although as many as 60% of
      infants have signs of GER, the role of GER in causing disease is difficult to
      elucidate. Despite new diagnostic tools to detect acid and nonacid reflux, our
      understanding of the relationship between reflux events and symptoms is complex.
      Furthermore, acid suppression, the mainstay of therapy for GER, increases the
      burden of nonacid reflux, which is already much higher in infants than in older
      children and which may worsen symptoms. Therefore, more conservative therapies
      are recommended for symptomatic infants. CONCLUSIONS AND RELEVANCE: Although GER
      is a common reason for visits to primary care providers and specialists, few data
      suggest that GER results in many of the symptoms to which it has been attributed.
      A strong shift away from acid-suppression therapy in infants has occurred because
      of the adverse effects, lack of efficacy, and increase of nonacid reflux burden
      relative to acid burden. Nonpharmacologic measures should be used whenever
      possible because most infant GER will resolve without intervention.

PMID- 24276412
TI  - Persistence of antihypertensive drug use in German primary care: a follow-up
      study based on pharmacy claims data.
AB  - PURPOSE: To study drug persistence for antihypertensive treatment considering
      typical patient behaviour including extended drug holidays or irregular repeat
      prescriptions. METHODS: We used prescription data from a German statutory health
      insurance to follow up patients for 4 years. Medication persistence was defined
      as the continued use of a specific drug class, therapy persistence as the
      continued use of any antihypertensive drug. We applied 2 different interval
      criteria within which a repeat prescription had to be issued: 180 and 360 days.
      RESULTS: A total of 9,513 patients started an antihypertensive therapy between
      2006 and 2008. Applying the 180-day (360-day) interval criterion, 28 % (66 %) of
      the patients starting therapy with a beta-blocker were still medication
      persistent after 4 years. The rates were similar for angiotensin-II receptor
      blockers (ARBs; 30 % and 69 % respectively) or angiotensin-converting enzyme
      (ACE) inhibitors (28 % and 61 % respectively). Looking at therapy persistence,
      these rates were 44 % (79 %) when an ACE inhibitor was the initial drug, 46 % (82
      %) for ARBs. On average, even of those who were defined as therapeutically
      persistent with the 360 days criterion, half received a repeat prescription
      within 96 days, three quarters within 131 days-with a median supply of 1.2 units
      per day and 1.25 defined daily doses. CONCLUSION: By applying more patient
      orientated criteria, we found that many patients were therapy-persistent and
      received a prescription at the appropriate time. Therapy persistence was nearly
      independent of the initial agent; thus, drug persistence may not be an argument
      in favour of choosing a certain drug as a first-line option.

PMID- 24276413
TI  - Almost a tragedy: severe methotrexate toxicity in a hemodialysis patient treated
      for ectopic pregnancy.
AB  - BACKGROUND: Methotrexate (MTX), an antimetabolite of folic acid, is the drug of
      choice for the nonsurgical management of ectopic pregnancy. MTX-related toxicity
      may include leukopenia, thrombocytopenia, pancytopenia, nausea, vomiting,
      stomatitis, mucositis, and liver and lung toxicity, depending primarily on the
      dosage of the drug and patients' renal function. Currently, the use of MTX in
      hemodialysis patients, even at a low dosage, is controversial, and no clear-cut
      guidelines are available. CASE REPORT: We report here a rare case of a life
      threatening complication characterized by severe pancytopenia and skin and
      mucosal injury, which developed in a young patient on hemodialysis after oral
      treatment with MTX for ectopic pregnancy. CONCLUSION: We conclude that even low
      dose MTX administration is not to be used in patients with renal insufficiency,
      and when no other therapeutic options are available we suggest taking several
      clinical measures to prevent or treat myelosuppression.

PMID- 24276415
TI  - Pubertal timing, menstrual irregularity, and mental health: results of a
      population-based study.
AB  - Reproductive events have a significant impact on women's lives. The aim of this
      study was to analyze the effects of age at menarche and current menstrual
      irregularity on psychological well-being and psychopathology. Data were collected
      in the context of the Finnish population-based Health 2000 study with self
      administered questionnaires, a home interview, and a clinical health examination.
      The Beck Depression Inventory (BDI-21), the General Health Questionnaire-12 (GHQ
      12), and the Composite International Diagnostic Interview (M-CIDI) were used to
      assess psychopathology. The relationships between age at menarche and current
      menstrual flow irregularity vs. BDI-21 and GHQ-12 scores and M-CIDI diagnoses
      were studied among 4,391 women aged 30 years and over. Negative, nonsignificant
      associations were found between age at menarche and BDI-21 and GHQ-12 scores.
      Young age at menarche was associated with increased risks of any recent mental
      disorder (OR = 0.894, p < 0.01), major depressive episode (OR = 0.900, p < 0.05),
      major depressive disorder (OR = 0.888; p < 0.05), and anxiety disorder (OR =
      0.892; p < 0.05). Menstrual irregularity was associated with BDI-21 (p < 0.001)
      and GHQ-12 (p < 0.05) scores, but not with any recent psychiatric diagnosis. Age
      at menarche and menstrual irregularity have an influence on mental health,
      particularly on mood and anxiety symptoms. Reproductive features (age at menarche
      and menstrual irregularity) should be paid attention to during psychiatric
      evaluations. 

PMID- 24276414
TI  - Association of changes in fitness and body composition with cancer mortality in
      men.
AB  - INTRODUCTION: Both baseline cardiorespiratory fitness and adiposity predict the
      risk of cancer mortality. However, the effects of changes in these two factors
      over time have not been evaluated thoroughly. The aim of this study was to
      examine the independent and joint associations of changes in cardiorespiratory
      fitness and body composition on cancer mortality. METHODS: The cohort consisted
      of 13,930 men (initially cancer-free) with two or more medical examinations from
      1974 to 2002. Cardiorespiratory fitness was assessed by a maximal treadmill
      exercise test, and body composition was expressed by body mass index (BMI) and
      percent body fat. Changes in cardiorespiratory fitness and body composition
      between the baseline and the last examination were classified into loss, stable,
      and gain groups. RESULTS: There were 386 deaths from cancer during an average of
      12.5 yr of follow-up. After adjusting for possible confounders and BMI, change
      hazard ratios (95% confidence intervals) of cancer mortality were 0.74 (0.57
      0.96) for stable fitness and 0.74 (0.56-0.98) for fitness gain. Inverse dose
      response relationships were observed between changes in maximal METs and cancer
      mortality (P for linear trend = 0.05). Neither BMI change nor percent body fat
      change was associated with cancer mortality after adjusting for possible
      confounders and maximal METs change. In the joint analyses, men who became less
      fit had a higher risk of cancer mortality (P for linear trend = 0.03) compared
      with those who became more fit, regardless of BMI change levels. CONCLUSIONS:
      Being unfit or losing cardiorespiratory fitness over time was found to predict
      cancer mortality in men. Improving or maintaining adequate levels of
      cardiorespiratory fitness appears to be important for decreasing cancer mortality
      in men.

PMID- 24276416
TI  - Factors influencing bladder management in male patients with spinal cord injury:
      a qualitative study.
AB  - STUDY DESIGN: Qualitative study using individual in-depth interviews. OBJECTIVES:
      The objective of this study was to explore the factors influencing the choice of
      bladder management for male patients with spinal cord injury (SCI). SETTING:
      Public hospitals in Malaysia. METHODS: Semistructured (one-on-one) interviews of
      17 patients with SCI; 7 were in-patients with a recent injury and 10 lived in the
      community. All had a neurogenic bladder and were on various methods of bladder
      drainage. Interviews were audio-recorded, transcribed verbatim and analyzed using
      thematic analyses. RESULTS: The choice of bladder management was influenced by
      treatment attributes, patients' physical and psychological attributes, health
      practitioners' influences and social attributes. Participants were more likely to
      choose a treatment option that was perceived to be convenient to execute and
      helped maintain continence. The influence of potential treatment complications on
      decision making was more variable. Health professionals' and peers' opinions on
      treatment options had a significant influence on participants' decision. In
      addition, patients' choices depended on their physical ability to carry out the
      task, the level of family support received and the anticipated level of social
      activities. Psychological factors such as embarrassment with using urine bags,
      confidence in self-catheterization and satisfaction with the current method also
      influenced the choice of bladder management method. CONCLUSION: The choice of
      bladder management in people with SCI is influenced by a variety of factors and
      must be individualized. Health professionals should consider these factors when
      supporting patients in making decisions about their treatment options.

PMID- 24276417
TI  - Bosentan reduces neuronal apoptosis following spinal cord ischemic reperfusion
      injury.
AB  - STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the effects of
      endothelin-receptor antagonist Bosentan on the spinal neural apoptosis in rats
      with ischemic reperfusion (IR) injury. SETTING: Department of Neurosurgery, the
      Second Affiliated Hospital, Xi'an Jiaotong University School of Medcine, Xi'an,
      Shaanxi Province, China: METHODS: Sprague-Dawley Rats were randomly divided into
      two groups, saline (IRS, n=48) and Bosentan (IRB, n=48) treatment, respectively,
      when reperfused in 6 h, 12 h, 24 h, 3 days, 5 days and 7 days.
      Immunohistochemical staining was used to assess endothelin-1 (ET-1), endothelin
      receptor type A (ETRA), endothelin receptor type B (ETRB), Bcl-2, Bax, Caspase-8,
      Caspase-9 and Caspase-3 expression. ET-1 and its receptor in spinal cord tissue
      were evaluated by real-time PCR. Plasma ET-1 concentration was also detected
      using radioimmunoassay. RESULTS: Compared with the group IRS, plasma
      concentration of ET-1 in group IRB was significantly increased at each time point
      (P<0.05) and peaked at 24 h (P<0.01). ETRB expression in group IRB was
      significantly higher than group IRS at each time point (P<0.05) and peaked at day
      3 (P<0.01). The difference in the expression of ETRA was not statistically
      significant in the group IRS and IRB (P>0.05). The apoptosis rate in group IRB
      was significantly decreased at each time point (P<0.05). The protein expressions
      of Bcl-2, Bax, Caspase-8, Caspase-9 and Caspase-3 were significantly increased in
      response to Bosentan treatment after IR. CONCLUSION: These results suggest
      Bosentan decreases apoptosis rate after IR injury in the spinal cord, possibly
      through the ET-1-ETRB signaling pathway.

PMID- 24276418
TI  - To cystoscope or not to cystoscope patients with traumatic spinal cord injuries
      managed with indwelling urethral or suprapubic catheters? That is the question!
AB  - STUDY DESIGN: Retrospective review of findings during cystourethroscopic
      surveillance of symptomatic and asymptomatic patients with indwelling urethral
      catheters (IUC) and suprapubic catheters (SPC) monitored between January 2003 and
      December 2008. OBJECTIVES: To audit and compare findings between symptomatic and
      asymptomatic patients and between SPC and IUC population. To systematically
      review the literature including the recent National Institute for Health and
      Clinical Excellence guidelines on cystoscopic surveillance. METHODS: Theater
      management system and the electronic patient records used to retrieve
      demographics, injury details and operative findings. RESULTS: Of 925 cystoscopies
      performed in 507 patients, 449 were performed in 277 patients with IUC/SPC. Only
      419 procedures (SPC 264; IUC 155) in 262 patients fit the inclusion criteria.
      Thirty procedures in fifteen non traumatic patients were excluded. Statistically
      there was no significant difference in incidence of findings between the
      symptomatic and asymptomatic group. Recurrent blockage of catheter was
      predominant in the SPC group and symptomatic urinary tract infections (UTIs) were
      the most common indications in the IUC group. In the asymptomatic group, there
      were 44 squamous metaplastic changes in 27 patients. Two of these patients had
      keratinizing variants. The duration of catheterization ranged from 20 months to
      27 years and mean of 13.7 years. The average duration between two cystoscopies in
      the symptomatic group was 16 months compared with an average 21 months in the
      asymptomatic group. CONCLUSION: Cystourethroscopic surveillance in high-risk
      patients with IUC/SPC is essential to diagnose and manage at an early-stage
      complications associated with IUC/SPC, minimize symptomatology, mitigate
      aggravation of complications, maintain good health and probably good quality of
      life.

PMID- 24276419
TI  - National hospitalization burden associated with spinal cord injuries in the
      United States.
AB  - OBJECTIVES: The objective of this study was to determine the national
      hospitalization burden of spinal cord injuries (SCIs) among adults in the United
      States. Factors predicting hospitalization outcomes including length of stay
      (LOS), total charges and discharge disposition of death were identified. SETTING:
      The study was conducted in the United States. METHODS: The 2009 Health Care
      Utilization Project Nationwide Inpatient Sample (HCUP-NIS) data were used in this
      study. Hospitalization outcomes among individuals with SCI were compared with a
      control group of individuals without SCI. Predictors of LOS, total charges and
      discharge disposition of death for SCI-related hospitalizations were determined
      using regression techniques. RESULTS: In 2009, there were a total of 11,848
      hospitalizations because of SCI in the United States. Hospitalizations because of
      SCIs had 2.5 times higher LOS (12.37 (+/- 0.51) versus 4.93 (+/- 0.09), P<0.0001)
      and 4 times higher average charges ($142,366 (+/-$7430.51) versus $35,011 (+/
      $1048.88), P<0.0001) as compared with those for the control group. The total
      national charge attributable to SCI-related hospitalizations was approximately
      $1.69 billion in 2009. Percentage of hospitalizations with discharge disposition
      of death was significantly higher among individuals with SCI as compared with
      those without SCI (5.77 versus 2.27%, P<0.0001). Different patient and hospital
      characteristics predicted LOS, total charges and discharge disposition of death
      for SCI-related hospitalizations. CONCLUSIONS: There is considerable inpatient
      burden associated with SCI in the United States. Inpatient LOS, charges and
      percentage of hospitalizations with discharge disposition of death were higher
      among individuals with SCI as compared with those without SCI.

PMID- 24276420
TI  - Structural and affinity analyses of g-quadruplex DNA aptamers for camptothecin
      derivatives.
AB  - We recently selected DNA aptamers that bind to camptothecin (CPT) and CPT
      derivatives from a 70-mer oligodeoxyribonucleotide (ODN) library using the
      Systematic Evolution of Ligands by EXponential enrichment (SELEX) method. The
      target-binding activity of the obtained 70-mer CPT-binding DNA aptamer, termed CA
      70, which contains a 16-mer guanine (G)-core motif (G3TG3TG3T2G3) that forms a
      three-tiered G-quadruplex, was determined using fluorescence titration. In this
      study, truncated fragments of CA-70 that all have the G-core motif, CA-40, -20, 
      19, -18A, -18B, -17, and -16, were carefully analyzed. We found that CA-40
      retained the target-binding activity, whereas CA-20, -19, and -18B exhibited
      little or no binding activities. Further, not only CA-18A but also the shorter
      length fragments CA-17 and -16 clearly retained the binding activity, indicating
      that tail strands of the G-quadruplex structure can significantly affect the
      target binding of G-quadruplex DNA aptamers. Further analyses using circular
      dichroism (CD) spectroscopy and fluorescence polarization (FP) assay were
      conducted to investigate the structure and affinity of G-quadruplex DNA aptamers.

PMID- 24276422
TI  - What Goes around Comes around-A Comparative Study of the Influence of Chemical
      Modifications on the Antimicrobial Properties of Small Cyclic Peptides.
AB  - Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine
      high antibacterial activity with rapid cell killing kinetics, but show low
      toxicity in human cell lines. The peptides fulfil the structural requirements for
      membrane interaction such as high amphipathicity and cationic charge, but
      membrane permeabilisation, which is the most common mode of action of
      antimicrobial peptides (AMPs), could not be observed. Our current studies focus
      on elucidating a putative membrane translocation mechanism whereupon the peptides
      might interfere with intracellular processes. These investigations require
      particular analytical tools: fluorescent analogues and peptides bearing
      appropriate reactive groups were synthesized and characterized in order to be
      used in confocal laser scanning microscopy and HPLC analysis. We found that
      minimal changes in both the cationic and hydrophobic domain of the peptides in
      most cases led to significant reduction of antimicrobial activity and/or changes
      in the mode of action. However, we were able to identify two modified peptides
      which exhibited properties similar to those of the cyclic parent hexapeptide and
      are suitable for subsequent studies on membrane translocation and uptake into
      bacterial cells. 

PMID- 24276421
TI  - Clinical pharmacology of furosemide in neonates: a review.
AB  - Furosemide is the diuretic most used in newborn infants. It blocks the Na+-K+-2Cl
      symporter in the thick ascending limb of the loop of Henle increasing urinary
      excretion of Na+ and Cl-. This article aimed to review the published data on the
      clinical pharmacology of furosemide in neonates to provide a critical,
      comprehensive, authoritative and, updated survey on the metabolism,
      pharmacokinetics, pharmacodynamics and side-effects of furosemide in neonates.
      The bibliographic search was performed using PubMed and EMBASE databases as
      search engines; January 2013 was the cutoff point. Furosemide half-life (t1/2) is
      6 to 20-fold longer, clearance (Cl) is 1.2 to 14-fold smaller and volume of
      distribution (Vd) is 1.3 to 6-fold larger than the adult values. t1/2 shortens
      and Cl increases as the neonatal maturation proceeds. Continuous intravenous
      infusion of furosemide yields more controlled diuresis than the intermittent
      intravenous infusion. Furosemide may be administered by inhalation to infants
      with chronic lung disease to improve pulmonary mechanics. Furosemide stimulates
      prostaglandin E2 synthesis, a potent dilator of the patent ductus arteriosus, and
      the administration of furosemide to any preterm infants should be carefully
      weighed against the risk of precipitation of a symptomatic patent ductus
      arteriosus. Infants with low birthweight treated with chronic furosemide are at
      risk for the development of intra-renal calcifications. 

PMID- 24276424
TI  - Ultrasound assessment of bladder wall thickness as a screening test for detrusor
      instability.
AB  - PURPOSE: The aim of the current study was to evaluate the diagnostic accuracy of
      transvaginal ultrasound measurement of bladder wall thickness (BWT) in diagnosis
      of over active bladder (OAB). METHODS: The current prospective study was
      conducted at Ain Shams University Maternity Hospital over 2 years. Patients
      presented to the urogynecology outpatient clinic with symptoms of urinary
      frequency, urgency, nocturia and/or urge incontinence were included in this
      study. The allocated patients were divided into two groups; Group 1(study group):
      fifty (50) patients with urodynamic diagnosis of detrusor instability (OAB) were
      included. Group 2 (control): fifty (50) patients with urodynamic diagnosis of
      stress incontinence were included. Using a transvaginal probe, BWT was measured
      in three sites at the thickest part of (a) the dome of the bladder (b) the
      trigone, and (c) the anterior wall of the bladder. An average of the three
      measurements was considered as the mean bladder thickness. RESULTS: A total of
      100 patients with lower urinary symptoms were finally analyzed. There were no
      statistical significant differences between both groups regarding age, parity and
      body mass index, while there was statistically longer disease duration in group
      2. Excluding urgency, there was statistical significant difference (P < 0.001)
      regarding lower urinary tract symptoms namely frequency, urgency incontinence,
      coital incontinence and nocturia. Patients in group 1 were more positive to
      symptoms of frequency, urgency incontinence, and nocturia, while patients in
      group 2 were more positive regarding coital incontinence. The thickness of
      trigon, dome, anterior wall and mean BWT was significantly higher in group 1 when
      compared to group 2. Receiver operator characteristics curve was constructed for
      estimating the association between mean BWT and prediction of OAB in patients
      with lower urinary tract symptoms. Mean BWT at 4.78 mm was considered as best cut
      off value for prediction of OAB with sensitivity of 90 % and specificity of 78 %.
      Mean BWT was significantly associated with OAB > 4.78 mm as denoted by the
      significantly large area under the curve [AUC], AUC was 0.905. CONCLUSION: In
      women with lower urinary tract symptom, transvaginal ultrasounds measured mean
      BWT seems to be an effective non invasive diagnostic tool for prediction of OAB.

PMID- 24276425
TI  - Twice-daily dosing of gonadotropins does not improve embryo quality during in
      vitro fertilization cycles in women with polycystic ovary syndrome, when compared
      to once-daily dosing: a pilot study.
AB  - PURPOSE: To determine whether overexpression of the FSH receptor in polycystic
      ovary syndrome (PCOS) results in a relative deficiency of gonadotropins and poor
      oocyte and embryo quality during in vitro fertilization (IVF) cycles. Whether
      twice-daily dosing of gonadotropins could therefore result in improved embryo
      quality, by fixing this hypothesized relative deficiency of gonadotropins.
      METHOD: Embryos generated at a university-based fertility center in women with
      PCOS were compared from twice-daily dosing to once-daily dosing of gonadotropins
      during IVF cycles. Oocyte and embryo quality was compared. A single patient's
      embryos were included in the analysis from only one IVF cycle and all embryos
      from that cycle were included. 254 embryos were compared. RESULTS: Twice-daily
      vs. once-daily dosing of gonadotropins does not improve embryo or oocyte quality
      in women with PCOS. CONCLUSIONS: The defect in response to gonadotropins in PCOS
      is most likely due to an inherent defect in the ovary and not a relative
      deficiency of gonadotropins due to overexpression of the FSH receptors. More
      studies are needed to confirm this finding.

PMID- 24276426
TI  - Synthesis and anti-toxoplasmosis activity of 4-arylquinoline-2-carboxylate
      derivatives.
AB  - A one-step synthesis of 4-arylquinoline-2-carboxylates along with their
      antiprotozoal activity against the pathogenic parasite Toxoplasma gondii is
      reported. Mechanistic insights into the role of Lewis acid (silver triflate)
      versus Bronsted acid (triflic acid) catalysis are revealed clarifying aspects of
      the mechanism of the quinoline synthesis. 

PMID- 24276423
TI  - Dynamic Cross Talk between S1P and CXCL12 Regulates Hematopoietic Stem Cells
      Migration, Development and Bone Remodeling.
AB  - Hematopoietic stem cells (HSCs) are mostly retained in a quiescent non-motile
      mode in their bone marrow (BM) niches, shifting to a migratory cycling and
      differentiating state to replenish the blood with mature leukocytes on demand.
      The balance between the major chemo-attractants CXCL12, predominantly in the BM,
      and S1P, mainly in the blood, dynamically regulates HSC recruitment to the
      circulation versus their retention in the BM. During alarm situations, stress
      signals induce a decrease in CXCL12 levels in the BM, while S1P levels are
      rapidly and transiently increased in the circulation, thus favoring mobilization
      of stem cells as part of host defense and repair mechanisms. Myeloid cytokines,
      including G-CSF, up-regulate S1P signaling in the BM via the PI3K pathway.
      Induced CXCL12 secretion from stromal cells via reactive oxygen species (ROS)
      generation and increased S1P1 expression and ROS signaling in HSCs, all
      facilitate mobilization. Bone turnover is also modulated by both CXCL12 and S1P,
      regulating the dynamic BM stromal microenvironment, osteoclasts and stem cell
      niches which all functionally express CXCL12 and S1P receptors. Overall, CXCL12
      and S1P levels in the BM and circulation are synchronized to mutually control HSC
      motility, leukocyte production and osteoclast/osteoblast bone turnover during
      homeostasis and stress situations. 

PMID- 24276428
TI  - Potential for evolution of resistance to pheromones : Worldwide and local
      variation in chemical communication system of pink bollworm moth,Pectinophora
      gossypiella.
AB  - FemalePectinophora gossypiella (Saunders) from most of the desert cotton-growing
      areas of southern California emitted significantly more pheromone in 1984 and
      1985 than in preceding years (1982 and 1983). This increase amounted to almost
      20% by 1985. It is unlikely that this small change would represent effective
      resistance to disruptant pheromones, but this increase could reflect the result
      of selection pressure imposed by the use of mating disruption for population
      control. A worldwide survey of emitted pheromone from this species found that
      there was much more variation in the emission rate than the blend ratio of the
      two pheromone components. The emitted blend ratio was remarkably consistent over
      time (in southern California) and throughout the worldwide range of the insect.
      Small differences in the blend ratio that were detected probably have no major
      biological significance because of the relatively broad response spectrum of
      males to changes in the blend of pheromonal components. Populations of males did
      not consist of several phenotypes, each with a different preference for specific
      blend ratios. Rather, the broad response spectrum to blend ratios in a population
      can be attributed to variation in the response of any individual. Therefore,
      selection for a response phenotype that is narrowly tuned to the blend emitted by
      females may be difficult. 

PMID- 24276429
TI  - Degradation of juglone by soil bacteria.
AB  - Bacteria that can degrade juglone (5-hydroxy-1,4-naphthoquinone) were isolated
      from soil beneath black walnut trees. Autecological studies with one of these
      bacteria (Pseudomonas J1), demonstrated that it could grow rapidly using juglone
      as its sole source of carbon and energy. Using nonlinear regression analysis and
      the Monod equation, it was determined that this bacterium had a high affinity for
      juglone (K s = 0.95 MUg/ml).Pseudomonas J1 can also utilize other aromatic
      compounds from plants as its sole source of carbon and energy. Compounds such as
      chlorogenic acid, ferulic acid, gallic acid, and 2-hydroxy-1,4-naphthoquinone
      (Lawson) were rapidly degraded byPseudomonas J1. The rapid degradation of juglone
      and other suspected allelochemicals by soil bacteria make it unlikely that these
      compounds are important mediators of plant-plant interactions under natural
      conditions. 

PMID- 24276427
TI  - Gene polymorphism of beta-defensin-1 is associated with susceptibility to
      periodontitis in Japanese.
AB  - Periodontitis is a multifactorial disease associated with genetic and
      environmental factors. Single-nucleotide polymorphisms (SNPs) are associated with
      susceptibility to common diseases such as diabetes and periodontitis. Although
      the oral cavity is exposed to various organisms, the conditions are well
      controlled by innate and acquired immune systems. Antimicrobial peptides (AMPs)
      play an important role in the innate immune system; however, the association of
      AMP-SNPs with periodontitis has not been fully elucidated. This study
      investigated the relationship between AMP-SNPs and periodontitis in Japanese. One
      hundred and five Japanese subjects were recruited, which included patients with
      aggressive, severe, moderate and mild periodontitis, and age-matched healthy
      controls. Genomic DNA was isolated from peripheral blood and genotypes of SNPs of
      beta-defensin-1 and lactoferrin genes (DEFB1: rs1799946, rs1800972 and rs11362;
      and LTF: rs1126478) were investigated using the PCR-Invader assay. Protein level
      of AMPs in gingival crevicular fluid (GCF) was quantified by ELISA. Case-control
      studies revealed that the -44 CC genotype of DEFB1 (rs1800972) was associated
      with periodontitis (OR 2.51), particularly with severe chronic periodontitis (OR
      4.15) and with combined severe and moderate chronic periodontitis (OR 4.04). No
      statistical differences were found in other genotypes. The beta-defensin-1
      concentrations in GCF were significantly lower in subjects with the -44 CC
      genotype of DEFB1 than in those without this genotype. No significant differences
      between GCF concentrations of AMPs and other genotypes were detected. The -44 CC
      genotype of the beta-defensin-1 gene (DEFB1 rs1800972) may be associated with
      susceptibility to chronic periodontitis in Japanese. 

PMID- 24276430
TI  - Biological activity and tentative identification of flavonoid components in
      velvetleaf (Abutilon theophrasti Medik.) seed coats.
AB  - The biological activity of aqueous extracts of velvetleaf (Abutilon theophrasti
      Medik.) seed coats and their flavonoid components against three plant species and
      five soil fungi was investigated. Aqueous extracts slightly inhibited germination
      and significantly inhibited radicle growth of all plant species tested. Fungal
      growth was inhibited or not affected, depending on species, by aqueous extracts.
      The aqueous extracts were extracted into methanol and separated using paper
      chromatography for identification of compounds responsible for inhibition of
      seedling and fungal growth. Six flavonoid compounds were isolated and tentatively
      identified as delphinidin, cyanidin, quercetin, myricetin, (+)-catechin, and (-)
      epicatechin. Bioassays revealed that the flavonoid compounds significantly
      inhibited germination and radicle growth of all test species at a concentration
      of 1.0 mM. Individual flavonoids had variable effects on fungi but appeared to
      inhibit growth and sporulation of potential seed-decomposing fungi rather than
      "beneficial" fungi. These results indicate that the flavonoid complement of
      velvetleaf seed coats may function in a dual defensive role against competing
      seedlings and seed-attacking fungi. 

PMID- 24276431
TI  - Beneficial arthropod behavior mediated by airborne semiochemicals : III.
      Influence of age and experience on flight chamber responses ofMicroplitis
      demolitor wilkinson.
AB  - Heliothis zea (Boddie) larvae fed cowpea seedlings produced volatile
      semiochemicals to whichMicroplitis demolitor Wilkinson responded in a wind
      tunnel. However, mostM. demolitor females reared fromH. zea larvae fed an
      artificial diet were not responsive at emergence to the same volatile
      semiochemicals. A preflight contact with frass fromH. zea fed cowpea was needed
      to stimulate a response of sustained flight in a wind tunnel. The most consistent
      flight response was 7-10 days postemergence. Response resulting from both
      antennal and ovipositor contact with host frass during preflight stimulation was
      no better than from antennal contact alone. Chilling the parasitoid pupae
      rendered most of the emerging females unresponsive to volatile semiochemicals. 

PMID- 24276432
TI  - Beneficial arthropod behavior mediated by airborne semiochemicals : IV. Influence
      of host diet on host-oriented flight chamber responses ofMicroplitis demolitor
      Wilkinson.
AB  - Microplitis demolitor Wilkinson were reared fromHeliothis zea larvae fed either
      an artificial diet or a diet of cowpea seedlings. Responses of females from these
      two sources to semiochemicals from the insect hostcowpea complex were compared in
      a flight tunnel. Very limited responses were obtained from females reared from
      hosts fed artificial diet unless they first had preflight contact with frass from
      plant-fed hosts. Female parasite is reared from plant-fed hosts were generally
      responsive without preflight contact. Contact with cocoons containing frass of
      the plant fed host at the time of emergence was an important source of
      stimulation. It increased their subsequent responsiveness to the volatile
      semiochemicals of the insect host-plant complex. The cocoons of females reared
      from artificial diet-fed hosts were apparently lacking plant chemicals that are
      vital to their subsequent responsiveness. Imprinting of the adults at time of
      emergence from the cocoon is strongly indicated. 

PMID- 24276433
TI  - Beneficial arthropod behavior mediated by airborne semiochemicals : V. Influence
      of rearing method, host plant, and adult experience on host-searching behavior
      ofMicroplitis croceipes (Cresson), a larval parasitoid ofHeliothis.
AB  - Rearing the parasitoidM. croceipes on hosts fed cowpea-seedling leaves instead of
      artificial diet increased the percentage of oriented flights to odors of a cowpea
      seedling-H. zea complex in a flight tunnel. However, the increase in response was
      much stronger after adult females had searched a fresh plant-host complex just
      prior to a test. The host plant appears to be of major importance in the
      parasitoid-host relationship: host-plant species, growth phase, and part of the
      host plant influence the parasitoid's response in the flight tunnel. The
      percentage of inexperienced females responding to infested leaves was higher for
      4- to 5-day-old females than for 0- to 1-day-old females, while the response to
      uninfested flowers was equally high for both age groups. Olfactory experience
      with odors of an attractive plant-host complex increased the response to an
      unattractive plant-host complex. Possible implications of the results are
      discussed. 

PMID- 24276434
TI  - Volatile methyl ketone seed-germination inhibitors fromAmaranthus palmeri S.
      Wats. Residues.
AB  - The effects of nine methyl ketones previously identified in the mixture of
      volatiles released byAmaranthus palmeri (AMAPA) residues upon onion, carrot,
      AMAPA, and tomato seed germination were determined. Three-day exposures to these
      volatiles significantly inhibited germination of all assay seeds, and the degree
      of inhibition was dependent upon seed species, exposure time, and concentration.
      Based on the degree of inhibition observed in both time- and concentration
      dependent assays, the following activity series was obtained: 2-octanone, 2
      nonanone > 2-undecanone > 2-heptanone > 2-hexanone, 3-methyl-2-butanone, 2
      pentanone, 3-hydroxy-2-butanone > 2-butanone. The activities of these compounds
      appear to be additive and dependent on relative volatility and hydrophilicity. 

PMID- 24276435
TI  - Seed-germination inhibition by volatile alcohols and other compounds associated
      withAmaranthus palmeri residues.
AB  - Effects of 3-pentanone and eight low molecular weight aliphatic alcohols and
      aldehydes identifed in the mixtures of volatiles released byAmaranthus palmeri S.
      Wats. (AMAPA) residues were determined on germination of onion, carrot, AMAPA,
      and tomato seeds. Three-day exposures to these volatiles significantly inhibited
      germination of these assay seeds, and the inhibition was dependent upon exposure
      time and concentration. Based on the degree of inhibition observed in both time-
      and concentration-dependent assays, the following activity series was obtained: 2
      heptanol > 3-methyl-1-butanol, 1-hexanol > hexanal, 1-pentanol, 3-pentanone,
      acetaldehyde > ethanol, 2-methyl-1-propanol. The activities of this group of
      compounds with that of 2-heptanone appear to be additive and related to test
      compound volatility and hydrophilicity. 2-Heptanol and 2-heptanone also
      significantly inhibited the germination of other species, including
      shepherdspurse, soybean, lettuce, alfalfa, common purslane, oats, and lovegrass. 

PMID- 24276436
TI  - Contribution of Coulomb explosion to form factors and mosaicity spread in single
      particle X-ray scattering.
AB  - The Coulomb explosion of the octamer water cluster has been studied employing
      time-dependent density functional theory explicitly accounting for the laser
      field and thus not imposing any constraint on the interaction between the laser
      pulse and the cluster. We focus on the effects of electron density changes in the
      system under high-intensity (10(16) and 10(15) W cm(-2)) soft X-ray laser pulses
      and their fingerprint in the reciprocal space, namely the ultrafast changes in X
      ray diffuse scattering signals in k-space (in the investigated k-space range from
      10(-3) up to 10 A(-1)). The present simulations indicate that diffusional
      components in X-ray intensity changes propagate from low reciprocal resolution
      (resembling the small-angle X-ray scattering regime) to very high resolution (the
      wide-angle X-ray scattering regime) during the Coulomb explosion process. 

PMID- 24276437
TI  - Clinical and genetic aspects of hypophosphatasia in Japanese patients.
AB  - OBJECTIVE: We examined the clinical and genetic features of hypophosphatasia
      (HPP) in Japanese patients. HPP is a rare metabolic bone disorder of bone
      mineralisation caused by mutations in the liver/bone/kidney alkaline phosphatase
      (ALPL) gene, which encodes tissue-non-specific alkaline phosphatase isoenzyme. 
      METHODS: We retrospectively investigate the incidence and clinical features of 52
      patients with paediatric HPP who were born between 1999 and 2010. Mutations of
      the ALPL gene were analysed in 31 patients. RESULTS: The annual incidence of
      perinatal lethal HPP (PLH) was estimated to be 2-3/1 000 000 births. The most
      frequent clinical type was PLH followed by prenatal benign. In addition to bone
      symptoms, cerebral manifestations were frequently observed including convulsion,
      mental retardation, deafness and short stature with growth hormone deficiency.
      Respiratory failure was the most significant predictor of a poor prognosis for
      PLH. The first and second most frequent mutations in the ALPL gene were
      c.1559delT and c.T979C (p.F327L), respectively. The c.1559delT homozygous
      mutation was lethal with respiratory failure. Patients with the p.F327L compound
      heterozygous mutation had the different non-lethal type with short stature and a
      gradual improvement in ALP level and bone mineralisation. CONCLUSIONS: The most
      frequent clinical type was the PLH type with prognosis related to respiratory
      failure, biochemical/radiological changes and ALPL mutations. Cerebral
      manifestations frequently occurred. Genotype-phenotype correlations were
      associated with specific outcomes in the PLH type, whereas different clinical
      features were associated with the same genotype in the non-lethal type.

PMID- 24276438
TI  - Selection for efficiency of feed utilization in growing mice.
AB  - Selection was practised for improved feed efficiency (gain/feed intake) of mice
      on two alternative feeding regimes. In one set of lines animals were fed ad
      libitum, in the other set they were individually fed a fixed amount of feed
      (about 10% below the control ad libitum intake) which was not changed over
      generations. For each treatment, a pair of replicate lines (E) were selected on
      efficiency from 3-5 weeks of age for 8 generations and another pair (L) from 5-7
      weeks for 7 generations. A control line was maintained for both E and L lines. In
      terminal generations mice from each line were tested on each feeding regime, and
      carcasses of ad libitum fed mice were analysed.The realized heritability (within
      families) for efficiency averaged 13%, without much variation over treatments. In
      the E lines efficiency increased by about 18% of the control mean and in the L
      lines by about 60%, although absolute changes were small, and responses were
      similar on the two feeding regimes. Weights at the start of test decreased in the
      E lines and increased in the L lines; weights at the end of test increased in
      both.When tested on the alternative regimes, no interactions were detected for
      live weights, weight gains or efficiency; selection under fixed intake led to the
      same increase in appetite as did that under ad libitum.There were no interactions
      for carcass composition. Selection for efficiency led to an increase in fatness
      on both selection regimes and both weight ranges. 

PMID- 24276439
TI  - Genetic segregation in relation to chromosome pairing in tetraploid hybrids
      between Lolium perenne and L. multiflorum.
AB  - Segregation at one of the loci controlling tiller-base pigmentation was studied
      to determine the mode of inheritance in tetraploid hybrids between Lolium perenne
      and L. multiflorum. The results could be explained by tetrasomic inheritance and
      thus did not support previous reports of a degree of preferential chromosome
      pairing in this material. However, double reduction and aneuploidy may to some
      extent have masked any tendency to disomic segregation brought about by
      preferential pairing. Moreover, there was significant heterogeneity between
      families in the segregation ratios which may indicate genetically controlled
      differences in pairing behaviour. The results are related to previous cytological
      and genetic studies. 

PMID- 24276440
TI  - Genetic studies of frost resistance in wheat.
AB  - Genetic studies of frost resistance were performed on various wheat varieties
      using diallel, F2 monosomic and substitution analysis.A six-parental cross
      including reciprocals was carried out, and F1 hybrids and their parents were used
      for the freezing tests under controlled conditions. Both the general combining
      ability (GCA) and the specific combining ability (SCA) were significant,
      indicating additive and non-additive gene action in the inheritance of frost
      resistance. The high GCA?SCA ratio revealed a preponderance of additive genetic
      variance. No significant reciprocal differences were found between the reciprocal
      crosses. The variance/covariance graphical analysis indicated the partial
      dominance of frost sensitivity. Frost sensitive varieties had the largest number
      of dominant genes, while frost resistant varieties had the highest proportion of
      recessive genes. The magnitude of the additive component of variation was higher
      than that of the dominance component, and the overall measure of the degree of
      dominance was smaller than one, so average dominance is incomplete. The
      increasing and decreasing alleles are not equally frequent at all loci. In this
      set of wheat varieties the values of narrow and broad heritability are relatively
      high.F2 monosomic analysis of the winter wheat variety 'Arthur' crossed with the
      monosomics of 'Chinese Spring' revealed that the average frost resistance of all
      the 21 monosomics was lower than that of the disomic. F2 monosomic hybrids 5A,
      2B, 4B and 5D proved to be relatively frost resistant, while monosomics 3A, 3B
      and 6D were the most sensitive.The control of frost resistance in the set of
      chromosome substitution lines of the variety 'Cheyenne' into 'Chinese Spring'
      (with the exception of 2B) indicated that the genes responsible for the frost
      resistance of 'Cheyenne' are localised in chromosomes 5A, 7A, 4B, 5B, 4D and
      5D.The genetic basis of frost resistance and problems of analysis are discussed. 

PMID- 24276441
TI  - An evaluation of mitochondrial heterosis and in vitro mitochondrial
      complementation in wheat, barley and maize.
AB  - Two families each of wheat (Triticum aestivum L.), barley (Hordeum vulgare L.)
      and maize (Zea mays L.) were studied for mitochondrial heterosis and in vitro
      mitochondrial complementation. Inbred parents and their hybrids were compared for
      seedling heights and rate of oxygen uptake by the whole tissue to find out if the
      hybrids showed greater growth and respiratory activity at the seedling stage.
      Further comparisons were made by isolating mitochondria from the seedling tissues
      and measuring their ADP?0 ratio, respiratory control ratio and cytochrome c
      oxidase activity for mitochondrial heterosis. Mixtures of parental mitochondria
      were similarly compared with parental and hybrid mitochondria for in vitro
      mitochondrial complementation. No evidence for mitochondrial heterosis or in
      vitro mitochondrial complementation was found, nor any correlation between the
      different mitochondrial parameters, seedling heights or rates of oxygen uptake by
      seedling tissue. The suggested use of mitochondrial heterosis and in vitro
      mitochondrial complementation for plant breeding is discussed. 

PMID- 24276442
TI  - Mitochondrial DNA variation in maize plants regenerated during tissue culture
      selection.
AB  - Plants resistant to Helminthosporium maydis race T were obtained following
      selection for H. maydis pathotoxin resistance in tissue cultures of susceptible,
      Texas male-sterile (T) cytoplasm maize. The selected lines transmitted H. maydis
      resistance to their sexual progeny as an extranuclear trait. Of 167 resistant,
      regenerated plants, 97 were male fertile and 70 were classified male sterile for
      reasons that included abnormal plant, tassel, anther or pollen development. No
      progeny were obtained from these male-sterile, resistant plants. Male fertility
      and resistance to the Phyllosticta maydis pathotoxin that specifically affects T
      cytoplasm maize were co-transmitted with H. maydis resistance to progeny of male
      fertile, resistant plants. These three traits previously were associated only
      with the normal (N) male-fertile cytoplasm condition in maize. Three generations
      of progeny testing provided no indication that the cytoplasmic association of
      male sterility and toxin susceptibility had been broken by this selection and
      regeneration procedure. Restriction endonuclease analysis of mitochondrial DNA
      (mtDNA) revealed that three selected, resistant lines had distinct mtDNA
      organization that distinguished them from each other, from T and from N cytoplasm
      maize. Restriction patterns of the selected resistant lines were similar to those
      from T cytoplasm mtDNA; these patterns had not been observed in any previous
      analyses of various sources of T cytoplasm. The mtDNA analyses indicated that the
      male-fertile, toxin-resistant lines did not originate from selection of N
      mitochondrial genomes coexisting previously with T genomes in the T cytoplasm
      line used for selection. 

PMID- 24276443
TI  - Origin and differentiation of Aegilops triuncialis L. as determined by esterase
      isozyme analysis.
AB  - Banding patterns of esterase isozymes in Aegilops triuncialis (2n = 28, genome
      formula C(u)C(u)CC) and its putative parental species, Ae. umbellulata (2n = 14,
      C(u)C(u)) and Ae. caudata (2n = 14, CC), were studied by the gel isoelectric
      focusing method using pH 6-8 carrier ampholite. Zymogram phenotypes of both
      parents were quite uniform. Seven zymogram phenotypes (designated as phenotypes 1
      to 7) were found among the 260 strains of Ae. triuncialis examined. Of these
      phenotypes, phenotype 1 was identical to the zymogram phenotype produced by the
      ancestral species, Ae. umbellulata, and bands considered to have been derived
      from Ae. caudata were absent in this phenotype. Phenotype 3 had all bands of both
      parents. The other phenotypes differed greatly from phenotype 3. Therefore,
      phenotype 3 was considered to be most primitive of the 7 types, and the Ae.
      triuncialis strains which showed phenotype 3 to be the most primitive of the
      strains examined. If Ae. triuncialis originated as a hybrid between Ae.
      umbellulata and Ae. caudata, the zymogram phenotype must have been phenotype 3,
      in which the isozymes of both parental species are present. Whether the
      phenotypes other than type 3 were due to introgressive hybridization could not be
      verified, but they were considered in this article to be a consequence of a
      rearrangement of chromosomes. 

PMID- 24276444
TI  - Basis and extent of genetic variability among doubled haploid plants obtained by
      pollen culture in Nicotiana sylvestris.
AB  - All diploid plants (doubled-haploid plants: D.H.) regenerated by androgenesis
      from binucleated pollen grains in Nicotiana sylvestris differ genetically from
      the original line as far as morphological features and growth rates are
      concerned. This androgenic variation (A.V.) is under nuclear control and is
      transmitted continuously by some D.H. for at least four generations of selfing;
      other D.H. progenies segregate. Further androgeneses carried out on one single
      D.H. reveal a new variability and increase the drift from the original line. All
      results cannot be explained by the presence of residual heterozygosity in the
      original line, and we suggest that most of the A.V. could originate from changes
      that occur in the DNA of the vegetative pollen grain cell. D.H. resulting from
      endomitosis of the vegetative cell would be 'homozygous' and stable, whereas D.H.
      resulting from nuclear fusion between a vegetative and a generative cell would be
      'heterozygous' and would segregate in seeds through succeeding generations. 

PMID- 24276445
TI  - S-specific proteins in styles of self-incompatible Nicotiana alata.
AB  - A comparison of the stigma protein patterns of individual plants of the inbred-
      and cross-progenies in Nicotiana alata by isoelectric focusing revealed the
      presence of S-specific proteins. The S allele-protein relationship was found for
      three different S alleles. The S-specific proteins occurred in both stigma and
      stylar parts of the pistil whereas they were absent in leaves. In clone OWL the
      concentration of S-specific proteins in the stigma increased gradually during
      floral development. The shift from compatibility to incompatibility was not
      accompanied by an abrupt increase in concentration of the S-proteins. 

PMID- 24276446
TI  - Streptomycin resistant and sensitive somatic hybrids of Nicotiana tabacum +
      Nicotiana knightiana: correlation of resistance to N. tabacum plastids.
AB  - Protoplasts of Nicotiana tabacum SRI (streptomycin resistant) and of Nicotiana
      knightiana (streptomycin sensitive) were fused using polyethylene glycol
      treatment. From three heterokaryons 500 clones were obtained. From the 43 which
      were further investigated, 6 resistant, 3 sensitive, and 34 chimeric (consisting
      of resistant and sensitive sectors) calli were found. From eight clones, a total
      of 39 plants were regenerated and identified as somatic hybrids. Chloroplast type
      (N. tabacum = NT or N. knightiana = NK) in the plants was determined on the basis
      of the species specific EcoRI restriction pattern of the chloroplast DNA.
      Regenerates contained NT (13 plants) or NK (15 plants) plastids but only the
      plants with the NT chloroplasts were resistant to streptomycin. This finding and
      our earlier data on uniparental inheritance points to the chloroplasts as the
      carriers of the streptomycin resistance factor. 

PMID- 24276447
TI  - Central diabetes insipidus in children and young adults: etiological diagnosis
      and long-term outcome of idiopathic cases.
AB  - CONTEXT: Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50%
      of affected subjects. OBJECTIVE: The purpose of this study was to determine
      whether a systematic diagnostic workup could achieve better etiologic diagnosis
      in children and adolescents presenting with polyuria and polydipsia. DESIGN AND
      SETTING: This is a prospective study conducted at a tertiary referral center.
      Patients underwent clinical and endocrine evaluations every 6 months and
      neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine
      function and neuroimaging were also reassessed after adult height achievement.
      PARTICIPANTS: A total of 85 consecutive patients with CDI were enrolled at a
      median age of 7.5 years; those with idiopathic CDI were stratified based on
      pituitary stalk thickness. MAIN OUTCOME MEASURES: To establish the etiology of
      CDI, we determined the time lag between its onset and the specific diagnosis, the
      long-term impact on pituitary function, and the overall long-term outcomes.
      RESULTS: Of the subjects, 24 (28.2%) received an etiologic diagnosis at
      presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans
      cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were
      considered to have idiopathic disease and were followed until the median age of
      17.3 years. Neuroimaging identified 40 of 43 patients with self-limited
      inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the
      severity of which was significantly correlated to pituitary dysfunction. The
      probability of >10-year-survival without an anterior pituitary defect was related
      to the severity of pituitary stalk thickness, and 53% showed permanent anterior
      pituitary defects. Three patients developed Langerhans cell histiocytosis and 1
      developed Hodgkin lymphoma after a median of 9 and 13 years, respectively.
      CONCLUSIONS: A diagnostic etiology was achieved in 96% of patients with CDI. Risk
      stratification based on the degree of pituitary stalk thickness is of prognostic
      value for long-term outcomes including permanent pituitary dysfunction. New
      guidance is provided for the management of these patients.

PMID- 24276448
TI  - Lower serum endogenous secretory receptor for advanced glycation end product
      level as a risk factor of metabolic syndrome among Japanese adult men: a 2-year
      longitudinal study.
AB  - CONTEXT: Receptor for advanced glycation end products (RAGE) activation by its
      ligands is implicated in obesity-related metabolic disease and accelerated
      atherothrombosis. Circulating soluble (sRAGE) and/or endogenous secretory RAGE
      (esRAGE) may counteract the detrimental effects of RAGE. OBJECTIVE: This study
      aimed at determining the relationship between circulating RAGE and metabolic
      syndrome (MetS) incidence among Japanese adult men. METHODS: This 2-year
      longitudinal study included 426 Japanese men aged 30-83 years who had no MetS at
      baseline. Serum esRAGE and sRAGE were assayed by ELISA at baseline. Incident
      metabolic syndrome, defined according to the Asian cutoff based on the 2009
      criteria of the American Heart Association Scientific Statements, was evaluated
      after the 2-year follow-up. RESULTS: During the follow-up period, 55 participants
      (12.9%) had newly diagnosed MetS. In the multiple logistic models comparing MetS
      risk in the lowest with that in the highest tertile of baseline esRAGE, a high
      serum esRAGE level was found to be significantly associated with a low risk of
      MetS [odds ratios (95% confidence interval), 0.37 (0.14-0.95); P for trend =
      0.038] after adjusting for lifestyle and sociodemographic factors, serum high
      sensitivity C-reactive protein level, estimated glomerular filtration rate, and
      MetS components at baseline. Although sRAGE and esRAGE were strongly correlated
      (r(s) = 0.88), the sRAGE level was not associated with MetS incidence.
      CONCLUSIONS: A high circulating esRAGE level, but not sRAGE level, was associated
      with a low MetS incidence among Japanese adult men.

PMID- 24276449
TI  - Mosaicism in HIF2A-related polycythemia-paraganglioma syndrome.
AB  - CONTEXT: HIF2A germline mutations were known to cause congenital polycythemia.
      Recently, HIF2A somatic mutations were found in several patients with
      polycythemia and paraganglioma, pheochromocytoma, or somatostatinoma, suggesting
      the occurrence of a de novo postzygotic HIF2A mutation that has not been
      demonstrated clearly. PATIENTS: Patient 1 is a woman suffering from polycythemia
      diagnosed at the age of 16 years. She was operated on for a pheochromocytoma at
      45 years and for two abdominal paragangliomas at 59 years. She was also diagnosed
      with somatostatinoma. Patient 2 is a young boy who suffered from polycythemia
      since infancy. He underwent surgery for a nonfunctional adrenal paraganglioma at
      the age of 9 years. METHODS: We sequenced by Sanger and next-generation
      sequencing the HIF2A gene in DNA extracted from tumors, leukocytes, and buccal
      cells. RESULTS: In patient 1, we identified a somatic HIF2A mutation (c.1586T>C;
      p.Leu529Pro) in DNA extracted from both paragangliomas. The mutation was detected
      as a somatic mosaic in DNA extracted from somatostatinoma and was absent from
      germline DNA. In patient 2, we found an HIF2A heterozygous mutation (c.1625T>C;
      p.Leu542Pro) in the paraganglioma, but the mutation was also present as a mosaic
      in leukocyte DNA and in DNA extracted from buccal cells (3.3 and 8.96% of
      sequencing reads, respectively). Both mutations disrupt the hydroxylation domain
      of the HIF2alpha protein. CONCLUSIONS: Our study shows that HIF2A-related tumors
      are caused by postzygotic mutations occurring in early developmental stages.
      Potential germline mosaicism should be considered during the familial genetic
      counseling when an individual has been diagnosed with HIF2A-related polycythemia
      paraganglioma syndrome.

PMID- 24276450
TI  - The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic
      review and meta-analysis.
AB  - CONTEXT: Significant uncertainty remains surrounding the diagnostic accuracy of
      sonographic features used to predict the malignant potential of thyroid nodules.
      OBJECTIVE: The objective of the study was to summarize the available literature
      related to the accuracy of thyroid nodule ultrasound (US) in the prediction of
      thyroid cancer. METHODS: We searched multiple databases and reference lists for
      cohort studies that enrolled adults with thyroid nodules with reported diagnostic
      measures of sonography. A total of 14 relevant US features were analyzed.
      RESULTS: We included 31 studies between 1985 and 2012 (number of nodules studied
      18,288; average size 15 mm). The frequency of thyroid cancer was 20%. The most
      common type of cancer was papillary thyroid cancer (84%). The US nodule features
      with the highest diagnostic odds ratio for malignancy was being taller than wider
      [11.14 (95% confidence interval 6.6-18.9)]. Conversely, the US nodule features
      with the highest diagnostic odds ratio for benign nodules was spongiform
      appearance [12 (95% confidence interval 0.61-234.3)]. Heterogeneity across
      studies was substantial. Estimates of accuracy depended on the experience of the
      physician interpreting the US, the type of cancer and nodule (indeterminate), and
      type of reference standard. In a threshold model, spongiform appearance and
      cystic nodules were the only two features that, if present, could have avoided
      the use of fine-needle aspiration biopsy. CONCLUSIONS: Low- to moderate-quality
      evidence suggests that individual ultrasound features are not accurate predictors
      of thyroid cancer. Two features, cystic content and spongiform appearance,
      however, might predict benign nodules, but this has limited applicability to
      clinical practice due to their infrequent occurrence.

PMID- 24276451
TI  - Lipopolysaccharide-binding protein plasma levels in children: effects of
      obstructive sleep apnea and obesity.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been linked to obesity,
      inflammation, and metabolic syndrome. The gut microbiota, which serves as
      reservoir for bacterial lipopolysaccharides (LPS), could be altered by OSA and
      trigger inflammation. LPS-binding protein (LBP) serves as a surrogate marker of
      underlying low-grade endotoxemia by LPS from the gut. We hypothesized that
      systemic LBP levels would be higher in obese children and in those with OSA.
      METHODS: Consecutive snoring and nonsnoring children (mean age 6.8 +/- 1.3 y)
      were included after overnight polysomnography, and fasting levels of lipids,
      insulin glucose, and high-sensitivity C-reactive protein were obtained. Children
      were subdivided into four subgroups based on the presence of obesity or OSA.
      Plasma LBP levels were assayed using ELISA. RESULTS: Of 219 participants,
      nonobese controls had the lowest levels of LBP, and the presence of obesity
      without OSA was associated with significant LBP increases. Nonobese children with
      OSA exhibited increased LBP levels, with obese children with OSA demonstrating
      the highest LBP levels of all four groups. Furthermore, LBP was independently
      associated with body mass index and with measures of OSA severity as well as with
      metabolic dysfunction, particularly insulin resistance as indicated by the
      homeostasis model assessment of insulin resistance. CONCLUSIONS: Systemic low
      level endotoxemia and resultant systemic inflammation is present in children who
      are either obese or suffer from OSA and is particularly prominent when both
      conditions are present. We postulate that disrupted sleep and other factors
      facilitating obesity such as a high-fat diet may disrupt the gut microbiome and
      lead to increased systemic LPS levels with resultant inflammation, promoting
      downstream metabolic dysfunction.

PMID- 24276452
TI  - Determination of the optimal time interval for repeat evaluation after a benign
      thyroid nodule aspiration.
AB  - INTRODUCTION: The optimal timing for repeat evaluation of a cytologically benign
      thyroid nodule greater than 1 cm is uncertain. Arguably, the most important
      determinant is the disease-specific mortality resulting from an undetected
      thyroid cancer. Presently there exist no data that evaluate this important end
      point. METHODS: We studied the long-term status of all patients evaluated in our
      thyroid nodule clinic between 1995 and 2003 with initially benign fine-needle
      aspiration (FNA) cytology. The follow-up interval was defined from the time of
      the initial benign FNA to any one of the following factors: thyroidectomy, death,
      or the most recent clinic visit documented anywhere in our health care system. We
      sought to determine the optimal timing for repeat assessment based on the
      identification of falsely benign malignancy and, most important, disease-related
      mortality due to a missed diagnosis. RESULTS: One thousand three hundred sixty
      nine patients with 2010 cytologically benign nodules were followed up for an
      average of 8.5 years (range 0.25-18 y). Thirty deaths were documented, although
      zero were attributed to thyroid cancer. Eighteen false-negative thyroid
      malignancies were identified and removed at a mean 4.5 years (range 0.3-10 y)
      after the initial benign aspiration. None had distant metastasis, and all are
      alive presently at an average of 11 years after the initial falsely benign FNA.
      Separate analysis demonstrates that patients with initially benign nodules who
      subsequently sought thyroidectomy for compressive symptoms did so an average of
      4.5 years later. CONCLUSIONS: An initially benign FNA confers negligable
      mortality risk during long-term follow-up despite a low risk of identifying
      several such nodules as thyroid cancer. Because such malignancies appear
      adequately treated despite detection at a mean 4.5 years after falsely benign
      cytology, these data support a recommendation for repeat thyroid nodule
      evaluation 2-4 years after the initial benign FNA.

PMID- 24276453
TI  - Thyrotropin secretion in healthy subjects is robust and independent of age and
      gender, and only weakly dependent on body mass index.
AB  - CONTEXT: Studies of the influence of sex, age, and body weight on TSH secretion
      are not unanimous. Most reports are based on a single TSH measurement; studies
      using frequent blood sampling are scarce and include a limited number of selected
      subjects. OBJECTIVE: The goal was to investigate TSH dynamics in 117 healthy
      adults. METHODS: TSH was measured by a sensitive immunofluorometric assay.
      Secretion parameters were quantified by automated deconvolution, approximate
      entropy [ApEn], spikiness, and diurnal properties. RESULTS: Mean age was 43 years
      (range, 22-77 y). Mean body mass index (BMI) was 26.8 kg/m(2) (range, 18.3-39.4
      kg/m(2)). Daily TSH secretion was 45.4 mU/L (range, 8.0-207 mU/L). There were no
      sex differences in secretion parameters, including pulse frequency; basal,
      pulsatile, and total secretion; pulse mode; half life; pulse regularity; ApEn;
      spikiness; and nycthemeral properties. BMI was positively related to basal
      secretion. Total secretion correlated negatively with free T4 (R = 0.225; P =
      .018). The onset of the nocturnal surge was delayed by increasing BMI and
      advanced by increasing age. ApEn and spikiness correlated positively with age,
      especially in men. The 9 am sample correlated strongly with the total 24-hour
      secretion, explaining two-thirds of the variability. CONCLUSION: This study shows
      that the 24-hour TSH secretion in healthy volunteers is stable and robust and not
      influenced by sex, BMI, and age. ApEn in the elderly, especially men, is
      increased, pointing to a less tight feedback control. Furthermore, aging is
      associated with advance shifting of the TSH rhythm, which is a phenomenon also
      observed in other biological rhythms.

PMID- 24276454
TI  - Comparative risk of fracture in men and women with HIV.
AB  - CONTEXT: Men and women with HIV have an increased risk of fracture compared with
      individuals without HIV; however, it is unknown if women with HIV fracture at
      higher rates than men. OBJECTIVE: We aimed to compare the incidence rates (IR) of
      fractures between men and women with HIV. DESIGN: The study was designed as a
      cohort study, examining medical records from November 2001 to August 2012.
      SETTING: The study was performed using records from two tertiary-care hospitals
      in Boston, Massachusetts. PATIENTS: The study patients were adults with HIV: this
      was defined by diagnosis codes for HIV on two visits, at least one prescription
      for antiretroviral therapy, and at least 18 years of age. INTERVENTION: IRs per
      1000 person-years of all fractures and fractures at osteoporotic sites were
      calculated. We calculated IRs within age and gender strata and estimated IR
      ratios (IRR) between men and women. MAIN OUTCOME MEASURE: The main outcome
      measure was fracture at any site. RESULTS: We identified a cohort of 3161 HIV
      infected patients (869 women and 2292 men) with a total of 587 fractures. The IRR
      of all fractures was 1.00 (95% confidence interval [CI] 0.83-1.19) between men
      and women. The IR of fractures at osteoporotic sites among men was 15.2 (95% CI
      12.7-17.6) per 1000 person-years compared with 12.1 (95% CI 8.6-15.6) in women,
      with IRR of 1.26 (95% CI 0.90-1.75). Men had similar or higher IRs than women for
      osteoporotic site fractures across most age groups. CONCLUSIONS: This study found
      similar rates of fracture in men and women with HIV. Further studies validating
      these findings are required to determine whether men with HIV should be screened
      for osteoporosis.

PMID- 24276455
TI  - Synergistic cooperation between sunitinib and cisplatin promotes apoptotic cell
      death in human medullary thyroid cancer.
AB  - CONTEXT: Tyrosine kinase inhibitors represent a new treatment option for patients
      with advanced medullary thyroid cancer (MTC). However, cures have not been
      achieved with current available agents used in monotherapy. OBJECTIVE: Because
      RET has been shown to negatively regulate CD95 death receptor activation in
      preclinical models of RET-dependent MTC, we investigated the potential of the
      combination approach with the RET-targeting tyrosine kinase inhibitor sunitinib
      and cisplatin to enhance apoptosis activation through the extrinsic pathway.
      DESIGN: The effects of sunitinib and cisplatin were examined in human MTC cell
      lines harboring oncogenic RET mutations. Experiments were designed to determine
      drug effects on RET signaling, cell growth, apoptosis, autophagy, and tumor
      growth in mice and to investigate the mechanisms of the drug interaction.
      RESULTS: Sunitinib and cisplatin synergistically inhibited the growth of MZ-CRC-1
      cells harboring the RET M918T activating mutation. The combination enhanced
      apoptosis activation through CD95-mediated, caspase-8-dependent pathway.
      Moreover, sunitinib induced a severe perturbation of the autophagic flux
      characterized by autophagosome accumulation and a remarkable lysosomal
      dysfunction, which was further enhanced, with lysosomal leakage induction, by
      cisplatin. Administration of the drug combination to mice xenografted with MZ-CRC
      1 cells improved the antitumor efficacy, as compared with single-agent
      treatments, inducing complete responses in 30% of the treated mice, a significant
      increase in caspase-3 activation (P < .01 vs cisplatin, and P < .0005 vs
      sunitinib) and apoptosis in tumor cells. CONCLUSIONS: Addition of cisplatin to
      sunitinib potentiates apoptotic cell death and has promising preclinical activity
      in MTCs harboring the RET M918T oncogene.

PMID- 24276456
TI  - Severe abdominal aortic calcification in older men is negatively associated with
      DKK1 serum levels: the STRAMBO study.
AB  - CONTEXT: Experimental data show that dickkopf-1 (DKK1) may be involved in the
      regulation of arterial calcification. However, clinical data on the association
      between serum DKK1 levels and severity of abdominal aortic calcification (AAC)
      are scarce. OBJECTIVE: Our aim was to determine the association between serum
      DKK1 concentration and AAC severity in men. DESIGN: This is a cross-sectional
      analysis in the STRAMBO cohort. SETTING: The cohort was recruited from the
      general population. PARTICIPANTS: We examined 1139 male volunteers aged 20 to 87
      years. No specific exclusion criteria were used. INTERVENTIONS: We collected
      blood samples and assessed AAC severity on the lateral spine scans obtained by a
      Discovery A Hologic device using the semiquantitative Kauppila score. MAIN
      OUTCOME MEASURES: We tested the hypothesis that low DKK1 levels are associated
      with AAC severity in men. RESULTS: In men aged 20 to 60 years, serum DKK1 levels
      were not associated with other variables. In men aged 60 years and older, lower
      DKK1 levels were associated with higher odds of severe AAC (AAC score >5). After
      adjustment for confounders, odds of severe AAC increased with decreasing DKK1
      levels (odds ratio = 1.42, 95% confidence interval = 1.13-1.79, P < .005) and was
      higher below vs above the median DKK1 level (odds ratio = 2.19, 95% confidence
      interval = 1.37-3.49, P < .005). Heavy smoking, hypertension, ischemic heart
      disease, and elevated levels of fibroblast growth factor 23 were associated with
      severe AAC significantly, independently of DKK1 and additively with low DKK1
      levels. CONCLUSION: In older men, lower serum DKK1 levels are associated with
      severe AAC regardless of age and other potential confounders.

PMID- 24276457
TI  - The effect of extent of surgery and number of lymph node metastases on overall
      survival in patients with medullary thyroid cancer.
AB  - CONTEXT: Total thyroidectomy with central lymph node dissection is recommended in
      patients with medullary thyroid cancer (MTC). However, the relationship between
      disease severity and extent of resection on overall survival remains unknown.
      OBJECTIVE: The aim of the study was to identify the effect of surgery on overall
      survival in MTC patients. METHODS: Using data from 2968 patients with MTC
      diagnosed between 1998 and 2005 from the National Cancer Database, we determined
      the relationship between the number of cervical lymph node metastases, tumor
      size, distant metastases, and extent of surgery on overall survival in patients
      with MTC. RESULTS: Older patient age (5.69 [95% CI, 3.34-9.72]), larger tumor
      size (2.89 [95% CI, 2.14-3.90]), presence of distant metastases (5.68 [95% CI,
      4.61-6.99]), and number of positive regional lymph nodes (for >=16 lymph nodes,
      3.40 [95% CI, 2.41-4.79]) were independently associated with decreased survival.
      Overall survival rate for patients with cervical lymph nodes resected and
      negative, cervical lymph nodes not resected, and 1-5, 6-10, 11-16, and >=16
      cervical lymph node metastases was 90, 76, 74, 61, 69, and 55%, respectively.
      There was no difference in survival based on surgical intervention in patients
      with tumor size <= 2 cm without distant metastases. In patients with tumor size >
      2.0 cm and no distant metastases, all surgical treatments resulted in a
      significant improvement in survival compared to no surgery (P < .001). In
      patients with distant metastases, only total thyroidectomy with regional lymph
      node resection resulted in a significant improvement in survival (P < .001).
      CONCLUSIONS: The number of lymph node metastases should be incorporated into MTC
      staging. The extent of surgery in patients with MTC should be tailored to tumor
      size and distant metastases.

PMID- 24276458
TI  - Assessment of thyroid function during first-trimester pregnancy: what is the
      rational upper limit of serum TSH during the first trimester in Chinese pregnant
      women?
AB  - CONTEXT: Guidelines of the American Thyroid Association (ATA) proposed that the
      upper limit of the TSH reference range should be 2.5 mIU/L in first trimester,
      but the reported ranges in China are significantly higher. OBJECTIVE: Our
      objective was to establish a rational reference range of serum TSH for diagnosis
      of subclinical hypothyroidism in the first trimester of pregnant women in China.
      DESIGN: We screened 4800 pregnant women in the first trimester and 2000 women who
      planned to become pregnant and evaluated 535 pregnant women in follow-up visits
      during the second and third trimester. RESULTS: Median concentrations of serum
      TSH decreased significantly from the seventh week of gestation. The median of TSH
      from 4 to 6 weeks was significantly higher than from 7 to 12 weeks (2.15 [0.56
      5.31] mIU/L vs 1.47 [0.10-4.34] mIU/L, P<.001); however, there was no significant
      difference compared with nonpregnant women (2.07 [0.69-5.64] mIU/L; P=.784). The
      median of free T4 was not significantly altered in the first trimester. The
      prevalence of subclinical hypothyroidism in the 4800 pregnant women was 27.8% on
      the diagnostic criteria of TSH>2.5 mIU/L and 4.0% using the reference interval
      derived by our laboratory (0.14-4.87 mIU/L).Additionally, of 118 pregnant women
      who had serum TSH>2.5 mIU/L in the first trimester, only 30.0% and 20.3% of them
      at the 20th and 30th week of gestation had TSH>3.0 mIU/L. CONCLUSIONS: The
      reference range for nonpregnant women can be used for the assessment of pregnant
      women at 4 to 6 weeks of gestation. The upper limit of serum TSH in the first
      trimester was much higher than 2.5 mIU/L in Chinese pregnant women.

PMID- 24276459
TI  - The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic
      adults.
AB  - CONTEXT: Hyperhomocysteinemia is an independent risk factor for premature
      atherosclerosis and thromboembolism. 25-Hydroxyvitamin D [25(OH)D] may modulate
      the expression of genes involved in homocysteine metabolism. OBJECTIVE: Little is
      known about the relationship between homocysteine and 25(OH)D. We hypothesized an
      inverse and nonlinear association between 25(OH)D and homocysteine. DESIGN: We
      analyzed data from the continuous National Health and Nutrition Examination
      Survey 2001-2006 for asymptomatic adults (>=18 y). SETTING: Linear regression
      models with spline adjusted for cardiovascular disease risk factors were used to
      explore nonlinearity. MAIN OUTCOMES MEASURE: Mean change (beta-coefficients with
      95% confidence intervals) in homocysteine was reported per 10 ng/mL change in
      25(OH)D. RESULTS: Mean (SD) age and homocysteine levels of 14 630 participants
      were 47.2 (20) years and 8.8 (4.7) MUmol/L, respectively, whereas the median
      (interquartile range) of 25(OH)D was 21 (15-27) ng/mL. Without using spline, we
      observed an inverse relation between homocysteine and 25(OH)D both in simple [
      0.25 (-0.34 to -0.02) MUmol/L] and multivariable [-0.13 (-0.18 to -0.01) MUmol/L]
      regression. With spline, in a univariate model, an increase in 25(OH)D was
      associated with a significant decrease in homocysteine [-0.56 (-0.75 to -0.37)
      MUmol/L] until 25(OH)D reaches but not if above its median (21 ng/mL). Similarly,
      in multivariable spline models, the inverse relationship between homocysteine and
      25(OH)D remain significant [-0.49 (-0.67 to -0.31) MUmol/L] only below the
      population median of 25(OH)D. CONCLUSIONS: From a large community-based cohort of
      asymptomatic adults, we found an inverse relation between 25(OH)D and
      homocysteine among those with 25(OH)D concentration of 21 ng/mL or less. We did
      not observe any statistical decrease in homocysteine once 25(OH)D concentration
      rose above 21 ng/mL.

PMID- 24276460
TI  - Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable
      pharmacodynamics and pharmacokinetics in older men and postmenopausal women.
AB  - BACKGROUND: Odanacatib is a cathepsin K inhibitor in development for the
      treatment of osteoporosis. Evaluation of therapies to ensure that treatment
      effects are relevant regardless of sex is clinically important. METHODS: In this
      double-blind, randomized controlled trial, older men (aged 50-75 years) and
      postmenopausal women (aged 45-75 years) were given odanacatib 50 mg once weekly
      or placebo for 4 weeks. Pharmacodynamic (PD) evaluation measured weighted average
      inhibition (WAI) of urine amino-terminal cross-linked telopeptide of type I
      collagen/creatinine (uNTx/Cr) after odanacatib administration. Pharmacokinetic
      (PK) parameter data were collected, and an analysis of sex as a factor in the
      PK/PD relationship was conducted. Adverse events were monitored. The hypotheses
      were that WAI of uNTx/Cr would be >40% (including >40% for the lower limit of the
      90% confidence intervals [CIs]) for older men and postmenopausal women, that
      there would be no important differences in area under the curve from 0 to 168
      hours (AUC0-168 h) between men and women, and that odanacatib would be safe and
      well tolerated. RESULTS: A total of 44 subjects (32 men and 12 women) were
      randomized. The least squares mean WAI (uNTx/Cr) at week 4 was 42.8% (90% CI,
      35.5%-49.3%) for men and 42.7% (90% CI, 30.3%-52.9%) for women; mean values were
      >40%, but lower bounds were <40% as prespecified in the primary hypothesis. The
      differences among men and women in PD parameters were not meaningful (0.1; 90%
      CI, -14.7 to 14.9). PK parameters for both groups were comparable (geometric mean
      ratio of AUC0-168 h, 0.90; 90% CI, 0.75-1.07). A PK/PD analysis found that the
      EC50 and maximum fractional inhibition were similar in male and female subjects.
      There were no notable or serious adverse events in this study. CONCLUSIONS:
      Although the primary hypothesis was not met, there were no clinically meaningful
      differences in PD, PK, or PK/PD parameters between older men and postmenopausal
      women, supporting further research on odanacatib (50 mg once weekly) as a
      treatment for male osteoporosis. Odanacatib was generally well tolerated.

PMID- 24276461
TI  - Negative effects of progesterone receptor isoform-A on human placental activity
      of the noncanonical NF-kappaB signaling.
AB  - CONTEXT: Progesterone (P4)contributes to the maintenance of human pregnancy, in
      part by inhibiting activity of the human pro-labor genes CRH and cyclooxygenase-2
      (COX-2). However, the molecular mechanisms underlying the action of P4 remain
      poorly defined. We have shown that in human placenta, the constitutively
      activated noncanonical nuclear factor (NF)-kappaB pathway positively regulates
      CRH and COX-2, which is further stimulated by glucocorticoid receptor signaling.
      OBJECTIVE: We investigated the role of P4 receptor (PR) in the regulation of
      nuclear activity of v-rel avian reticuloendotheliosis viral oncogene homolog B
      (RelB)/NF-kappaB2 and, in turn, expression of placental CRH and COX-2. METHODS:
      We used a variety of techniques including gene silencing, ectopic expression,
      chromatin immunoprecipitation, Western blot, quantitative RT-PCR, and
      immunohistochemical staining assays in human placental tissues and primary
      culture of human cytotrophoblast. RESULTS: We identified PR isoform-A (PR-A) as
      the only isoform of PR produced in human placenta. PR-A levels were lower in term
      placenta than in midterm placenta. Depletion of PR-A by short interfering RNA
      derepressed inhibition of CRH and COX-2 by P4 and the synthetic progestin 17alpha
      hydroxyprogesterone caproate. Overexpression of PR-A inhibited transcription of
      CRH and COX-2, which was further downregulated by treatment with P4 or 17alpha
      hydroxyprogesterone caproate. Such an inhibition was mediated by a negative
      functional interaction of PR-A with the activity of RelB/NF-kappaB2. CONCLUSION:
      P4 inhibits the pro-labor genes CRH and COX-2 via PR-A repression of the
      noncanonical NF-kappaB signaling in human placenta. Characterization of these
      pathways may identify potential drug targets for prevention of preterm birth.

PMID- 24276462
TI  - Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a
      potential indicator of ovarian reserve.
AB  - CONTEXT: The interaction of advanced glycation end-products (AGEs) with their
      cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian
      follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE
      (sRAGE), which neutralizes the action of AGEs and might exert a protective role
      on the follicular environment. OBJECTIVE: The objective of the study was to
      investigate whether serum or follicular fluid (FF) sRAGE levels are associated
      with markers of ovarian reserve. DESIGN, SETTING, AND PARTICIPANTS: Serum anti
      Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31
      reproductive-aged women. An additional 33 women who underwent oocyte retrieval
      for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA
      levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein
      levels were measured. MAIN OUTCOME MEASURES: Granulosa cell AMH and AMHR-II gene
      expression, serum and FF AMH and sRAGE protein concentration, and number of
      oocytes retrieved were measured. RESULTS: In the serum, sRAGE levels were
      negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not
      with age or serum AMH. The higher the FF sRAGE, the lower the number of
      international units of gonadotropin needed per cycle independent of age, BMI, or
      day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and
      the total dose of gonadotropins, FF sRAGE predicted the number of oocytes
      retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH
      levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF
      sRAGE and AMH or AMHR-II mRNA levels. CONCLUSION: These data support a
      relationship between FF sRAGE and measures of ovarian reserve. The pathological
      significance of the harmful inflammatory AGEs in follicular health clearly
      requires further investigation. Targeting AGEs might offer potential therapeutic
      options for the treatment of diminished ovarian response.

PMID- 24276463
TI  - Feeding and bone turnover in gastric bypass.
AB  - CONTEXT: Roux-en-Y gastric bypass (RYGB) is associated with high bone turnover.
      In healthy subjects, feeding causes acute reduction of bone resorption, which is
      regulated by several intestinal and pancreatic peptides. OBJECTIVE: Our objective
      was to assess bone turnover after feeding in patients with RYGB. DESIGN AND
      SETTING: This was a cross-sectional case-control study at a university hospital.
      PARTICIPANTS: Fifteen postmenopausal women who underwent RYGB 7.4 +/- 4.1 years
      previously were matched by age and body mass index with 15 nonoperated women
      (controls). MAIN OUTCOMES: Serum PTH, calcium, phosphorus, insulin, carboxy
      telopeptide (CTX), procollagen type I N-terminal propeptide (P1NP), and glucagon
      like peptide 2 (GLP-2) were measured while fasting and after a standard meal
      (SM). RESULTS: The fasting calcium, phosphorus, and PTH were similar in both
      groups and exhibited similar decreases after an SM. The fasting CTX level was
      higher in the RYGB than in the control group (0.589 +/- 0.18 vs 0.382 +/- 0.11
      ng/mL; P < .05) and fell to a nadir of 42.2% of the basal value in the RYGB and
      53.9% in controls (P < .05). The fasting and postprandial P1NP levels were
      similar in both groups and fell to a nadir of 85.8% in the RYGB and 89.3% in
      controls. Insulin and GLP-2 levels were similar during fasting in both groups.
      RYGB patients had exaggerated postprandial insulin and GLP-2 response compared
      with the controls with the insulin and GLP-2 area under the curve being
      significantly higher in the RYGB group. There was a significant negative
      correlation between the peak of insulin levels and the CTX changes. CONCLUSION:
      The acute reduction in bone resorption after feeding is preserved in RYGB and is
      even higher than in nonoperated subjects. This phenomenon is related to the
      increase of postprandial levels of insulin. These findings suggest a bone
      protecting mechanism in RYGB that may counteract the elevated bone resorption
      that occurs during fasting.

PMID- 24276465
TI  - MEN1 gene mutation and reduced expression are associated with poor prognosis in
      pulmonary carcinoids.
AB  - CONTEXT: MEN1 gene alterations have been implicated in lung carcinoids, but their
      effect on gene expression and disease outcome is unknown. OBJECTIVE: Our
      objective was to analyze MEN1 gene and expression anomalies in lung
      neuroendocrine neoplasms and their correlations with clinicopathologic data and
      disease outcome. DESIGN: We examined 74 lung neuroendocrine neoplasms including
      58 carcinoids and 16 high-grade neuroendocrine carcinomas (HGNECs) for MEN1
      mutations (n = 70) and allelic losses (n = 69), promoter hypermethylation (n =
      65), and mRNA (n = 74) expression. Results were correlated with disease outcome.
      RESULTS: MEN1 mutations were found in 7 of 55 (13%) carcinoids and in 1 HGNEC,
      mostly associated with loss of the second allele. MEN1 decreased expression
      levels correlated with the presence of mutations (P = .0060) and was also lower
      in HGNECs than carcinoids (P = .0024). MEN1 methylation was not associated with
      mRNA expression levels. Patients with carcinoids harboring MEN1 mutation and loss
      had shorter overall survival (P = .039 and P = .035, respectively) and low MEN1
      mRNA levels correlated with distant metastasis (P = .00010) and shorter survival
      (P = .0071). In multivariate analysis, stage and MEN1 allelic loss were
      independent predictors of prognosis. CONCLUSION: Thirteen percent of pulmonary
      carcinoids harbor MEN1 mutation associated with reduced mRNA expression and poor
      prognosis. Also in mutation-negative tumors, low MEN1 gene expression correlates
      with an adverse disease outcome. Hypermethylation was excluded as the underlying
      mechanism.

PMID- 24276464
TI  - Adipocyte mitochondrial function is reduced in human obesity independent of fat
      cell size.
AB  - CONTEXT: It has been suggested that mitochondrial dysfunction in adipocytes
      contributes to obesity-related metabolic complications. However, obesity results
      in adipocyte hypertrophy, and large and small adipocytes from the same depot have
      different characteristics, raising the possibility that obesity-related
      mitochondrial defects are an inherent function of large adipocytes. OBJECTIVE:
      Our goal was to examine whether obesity, independent of fat cell size and fat
      depot, is associated with mitochondria dysfunction. DESIGN: We compared adipocyte
      mitochondrial function using a cross-sectional comparison study design. SETTING:
      The studies were performed at Mayo Clinic, an academic medical center. PATIENTS
      OR OTHER PARTICIPANTS: Omental and/or abdominal subcutaneous adipose samples were
      collected from 20 age-matched obese and nonobese nondiabetic men and women
      undergoing either elective abdominal surgery or research needle biopsy.
      INTERVENTION: Interventions were not conducted as part of these studies. MAIN
      OUTCOME MEASURES: We measured mitochondrial DNA abundance, oxygen consumption
      rates, and citrate synthase activity from populations of large and small
      adipocytes (separated with differential floatation). RESULTS: For both omental
      and subcutaneous adipocytes, at the cell and organelle level, oxygen consumption
      rates and citrate synthase activity were significantly reduced in cells from
      obese compared with nonobese volunteers, even when matched for cell size by
      comparing large adipocytes from nonobese and small adipocytes from obese.
      Adipocyte mitochondrial content was not significantly different between obese and
      nonobese volunteers. Mitochondrial function and content parameters were not
      different between small and large cells, omental, and subcutaneous adipocytes
      from the same person. CONCLUSION: Adipocyte mitochondrial oxidative capacity is
      reduced in obese compared with nonobese adults and this difference is not due to
      cell size differences. Adipocyte mitochondrial dysfunction in obesity is
      therefore related to overall adiposity rather than adipocyte hypertrophy.

PMID- 24276466
TI  - The impact of nonhip nonvertebral fractures in elderly women and men.
AB  - CONTEXT: Nonhip nonvertebral fractures represent half of all osteoporotic
      fractures; however, their contribution to the burden of refracture and premature
      mortality is unclear. OBJECTIVES: To examine the risk and burden of subsequent
      fracture and mortality associated with an initial nonhip nonvertebral fracture.
      SETTING AND PARTICIPANTS: This is a prospective cohort from the Dubbo
      Osteoporosis Epidemiology Study, 1989-2010 of community dwelling participants
      aged 60+ with incident fractures. OUTCOME MEASURES: Relative risk of all
      subsequent fractures and age-adjusted standardized mortality ratios were
      calculated according to initial fracture type. The total burden of adverse events
      was assessed using competing risk models with four potential outcomes: mortality
      after initial fracture, mortality after subsequent fracture, subsequent fracture
      and alive, or event-free. RESULTS: Of the 952 fractures in women and 343 in men,
      over half were nonhip nonvertebral fractures (486 in women and 173 in men).
      Nonhip nonvertebral fractures were associated with increased risk of any
      subsequent fracture (1.95 [1.67-2.27] for women and 2.47 [1.82-3.35] for men),
      hip refracture (2.11 [1.04-4.28] for women and 2.63 [1.35-5.13] for men), and
      vertebral refracture (1.89 [1.43-2.48] for women and 2.13 [1.20-3.79] for men).
      More importantly, nonhip nonvertebral fractures were associated overall with 20%
      excess mortality for the first 5 years postfracture, of which approximately half
      were due to initial fracture and the remaining due to subsequent fractures.
      Proximal fractures were associated with increased mortality risk per se, whereas
      distal fractures were associated with increased mortality risk only in the group
      who sustained subsequent fractures. CONCLUSION: Nonhip nonvertebral fractures are
      associated with significant risk of subsequent fracture including hip and
      vertebral refracture, and premature mortality. Due to their high prevalence,
      about half of all subsequent fractures and a quarter of all fracture-related
      excess mortality were attributable to nonhip nonvertebral fracture. Thus nonhip
      nonvertebral fracture warrants early investigation and appropriate intervention.

PMID- 24276468
TI  - To adjust or not in studies on racial differences in hormone concentrations?
      Depends on the question!

PMID- 24276467
TI  - Germline prokineticin receptor 2 (PROKR2) variants associated with central
      hypogonadism cause differental modulation of distinct intracellular pathways.
AB  - INTRODUCTION: Defects of prokineticin pathway affect the neuroendocrine control
      of reproduction, but their role in the pathogenesis of central hypogonadism
      remains undefined, and the functional impact of the missense PROKR2 variants has
      been incompletely characterized. MATERIAL AND METHODS: In a series of 246
      idiopathic central hypogonadism patients, we found three novel (p.V158I, p.V334M,
      and p.N15TfsX30) and six already known (p.L173R, p.T260M, p.R268C, p.V274D,
      p.V331M, and p.H20MfsX23) germline variants in the PROKR2 gene. We evaluated the
      effects of seven missense alterations on two different prokineticin receptor 2
      (PROKR2)-dependent pathways: inositol phosphate-Ca(2+) (Gq coupling) and cAMP (Gs
      coupling). RESULTS: PROKR2 variants were found in 16 patients (6.5%). Expression
      levels of variants p.V158I and p.V331M were moderately reduced, whereas they were
      markedly impaired in the remaining cases, except p.V334M, which was significantly
      overexpressed. The variants p.T260M, p.R268C, and p.V331M showed no remarkable
      changes in cAMP response (EC50) whereas the IP signaling appeared more profoundly
      affected. In contrast, cAMP accumulation cannot be stimulated through the p.L173R
      and p.V274D, but IP EC50 was similar to wt inp.L173R and increased by 10-fold in
      p.V274D. The variant p.V334M led to a 3-fold increase of EC50 for both cAMP and
      IP. CONCLUSION: Our study shows that single PROKR2 missense allelic variants can
      either affect both signaling pathways differently or selectively. Thus, the
      integrity of both PROKR2-dependent cAMP and IP signals should be evaluated for a
      complete functional testing of novel identified allelic variants.

PMID- 24276469
TI  - Screening for oral cancer: U.S. Preventive Services Task Force recommendation
      statement.
AB  - DESCRIPTION: Update of the 2004 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for oral cancer. METHODS: The USPSTF reviewed the
      evidence on whether screening for oral cancer reduces morbidity or mortality and
      on the accuracy of the oral screening examination for identifying oral cancer or
      potentially malignant disorders that have a high likelihood of progression to
      oral cancer. POPULATION: This recommendation applies to asymptomatic adults aged
      18 years or older who are seen by primary care providers. This recommendation
      focuses on screening of the oral cavity performed by primary care providers and
      not dental providers or otolaryngologists. RECOMMENDATION: The USPSTF concludes
      that the current evidence is insufficient to assess the balance of benefits and
      harms of screening for oral cancer in asymptomatic adults.

PMID- 24276470
TI  - The up-regulation expression of APRIL is a marker of glottic malignant disease.
AB  - A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor
      (TNF) family. Recent studies have implied that APRIL is closely related to solid
      tumors and hematological tumors, indicating that APRIL could be a potential
      marker to diagnose glottic malignant disease. The purpose of this study was to
      investigate the difference of the APRIL mRNA and protein expression in glottic
      malignant disease, corresponding adjacent non-neoplastic tissues and glottic
      benign lesion, and detect the influence of different clinical parameter in
      glottic carcinoma. The APRIL mRNA expression in the glottic carcinoma,
      corresponding adjacent non-neoplastic tissues and glottic polypus tissue samples
      from patients was detected by qRT-PCR. Moreover, we studied the APRIL protein
      expression in pathological sections of other patients with glottic carcinoma or
      glottic polypus using immunohistochemistry. All the patients with different
      clinical parameter underwent surgery. Using qRT-PCR, we revealed an up-regulation
      of APRIL mRNA expression in glottic carcinoma as compared to glottic polypus and
      corresponding adjacent non-neoplastic tissues, but no significant difference with
      T stages, histopathological differentiation grade or lymph node metastasis in
      glottic carcinoma. The result of the immunohistochemistry was the same, with no
      influence of different clinical parameter in glottic carcinoma. These results
      strongly suggest that APRIL could be a potential diagnosed marker to distinguish
      glottic malignant disease from glottic benign lesion, and it may play an
      important role in the development of glottic malignant disease. 

PMID- 24276471
TI  - When is reoperative surgery not indicated for recurrent head and neck squamous
      cell carcinoma?

PMID- 24276472
TI  - Effect of atrazine, glyphosate and quinclorac on biochemical parameters, lipid
      peroxidation and survival in bullfrog tadpoles (Lithobates catesbeianus).
AB  - Increased use of pesticides worldwide has led to damage not only to natural
      ecosystems but also to nontarget species. This study assessed the effects of
      different concentrations of the herbicides atrazine, glyphosate, and quinclorac
      on biochemical parameters, lipid peroxidation, and survival in tadpoles of
      Lithobates catesbeianus (bullfrog). Two hundred eighty-eight tadpoles were
      acquired from a frog farm in the south of Brazil. All animals were kept in
      aquariums under controlled laboratory conditions for 7 days and exposed to
      commercial formulations of atrazine (5, 10, and 20 MUg/L), glyphosate (36, 72,
      and 144 MUg/L), and quinclorac (0.05, 0.10, and 0.20 MUg/L) for 7 days
      thereafter. The concentrations used in this study are similar to the levels of
      these herbicides found in natural water bodies. After exposure, gill, liver, and
      muscle samples were removed from each animal for quantitation of glycogen, total
      lipids, triglycerides, cholesterol, total proteins, and lipid peroxidation.
      Atrazine, glyphosate, and quinclorac exposure induced a significant decrease in
      levels of glycogen and total lipids in gill, liver, and muscle. Triglycerides
      levels in the gill increased after exposure to glyphosate, and decreased after
      exposure to atrazine and quinclorac; their levels in liver and muscle decreased
      on exposure to all herbicides. Cholesterol and total protein levels decreased in
      liver and muscle for all three herbicides. All tissues exhibited increased lipid
      peroxidation after exposure to all herbicides. In conclusion, exposure to the
      herbicides tested in this study induced significant changes in biochemical
      parameters and increased lipid peroxidation levels in tadpoles of L.
      catesbeianus. 

PMID- 24276473
TI  - NBD-based colorimetric and fluorescent turn-on probes for hydrogen sulfide.
AB  - Hydrogen sulfide (H2S) is an important endogenous signalling molecule and also an
      important environmental target for detection. New reaction-based colorimetric and
      fluorescent turn-on probes based on selective thiolyling of NBD (7-nitro-1,2,3
      benzoxadiazole) ether were explored for sensing of H2S in aqueous buffer. The
      syntheses of both probes are simple and quite straightforward. The probes are
      highly sensitive and selective toward H2S over other biologically relevant
      species. Probe 1 can be used to directly visualize H2S by the naked eye and shows
      more than 1000-fold fluorescence increase upon reaction with H2S. Probe 2 is a
      near-infrared fluorescent sensor for H2S at physiological pH. 

PMID- 24276474
TI  - Drugs for migraine.

PMID- 24276475
TI  - Mapping three-dimensional temperature in microfluidic chip.
AB  - Three-dimensional (3D) temperature mapping method with high spatial resolution
      and acquisition rate is of vital importance in evaluating thermal processes in
      micro-environment. We have synthesized a new temperature-sensitive functional
      material (Rhodamine B functionalized Polydimethylsiloxane). By performing optical
      sectioning of this material, we established an advanced method for visualizing
      the micro-scale 3D thermal distribution inside microfluidic chip with down to 10
      ms temporal resolution and 2 ~ 6  degrees C temperature resolution depending the
      capture parameters. This method is successfully applied to monitor the local
      temperature variation throughout micro-droplet heat transfer process and further
      reveal exothermic nanoliter droplet reactions to be unique and milder than bench
      top experiment.

PMID- 24276477
TI  - Bacterial community dynamics in a rotating biological contactor treating 2
      fluorophenol-containing wastewater.
AB  - One of the main factors affecting the performance of rotating biological
      contactors (RBC) is the biofilm characteristics. Therefore, a deep understanding
      of the microbial population dynamics and structure of the biofilm is mandatory if
      optimization of organic matter and nutrients removal is targeted. This study
      focused on the effects of organic shock loads of 2-fluorophenol (2-FP) on the
      microbial diversity present in an RBC biofilm. The RBC was seeded with activated
      sludge from a conventional wastewater treatment plant and was operated during 496
      days. During the first 126 days, the RBC was subjected to intermittent 2-FP
      shocks of 25 mg l(-1) and no degradation occurred. Therefore, the reactor was
      subsequently augmented with a 2-FP-degrading strain (FP1). Afterwards, the RBC
      had a stable performance when subjected to 2-FP shocks up to 50 mg l(-1) and to a
      starvation period, as indicated by removal of the compound. Denaturing gradient
      gel electrophoresis (DGGE) revealed large shifts in microbial communities present
      in the first and fifth stages, although no clear relation between the sample
      collection time and spatial factor was found. Phylogenetic affiliation of some
      predominant members was assessed by direct sequencing of correspondent DGGE
      bands. Affiliations to alpha-, beta- and delta-Proteobacteria were found. Several
      bacterial strains isolated from the reactor showed capacity for 2-FP degradation.
      Strain FP1 was successfully recovered from the biofilm by plating and by DGGE,
      reinforcing that bioaugmentation was successfully achieved. 

PMID- 24276476
TI  - Stepwise histone modifications are mediated by multiple enzymes that rapidly
      associate with nascent DNA during replication.
AB  - The mechanism of epigenetic inheritance following DNA replication may involve
      dissociation of chromosomal proteins from parental DNA and reassembly on daughter
      strands in a specific order. Here we investigated the behaviour of different
      types of chromosomal proteins using newly developed methods that allow assessment
      of the assembly of proteins during DNA replication. Unexpectedly, most chromatin
      modifying proteins tested, including methylases, demethylases, acetyltransferases
      and a deacetylase, are found in close proximity to PCNA or associate with short
      nascent DNA. Histone modifications occur in a temporal order following DNA
      replication, mediated by complex activities of different enzymes. In contrast,
      components of several major nucleosome-remodelling complexes are dissociated from
      parental DNA, and are later recruited to nascent DNA following replication.
      Epigenetic inheritance of gene expression patterns may require many aspects of
      chromatin structure to remain in close proximity to the replication complex
      followed by reassembly on nascent DNA shortly after replication. 

PMID- 24276478
TI  - Cinnamaldehyde/chemotherapeutic agents interaction and drug-metabolizing genes in
      colorectal cancer.
AB  - Cinnamaldehyde is an active monomer isolated from the stem bark of Cinnamomum
      cassia, a traditional oriental medicinal herb, which is known to possess marked
      antitumor effects in vitro and in vivo. The aim of the present study was to
      examine the potential advantages of using cinnamaldehyde in combination with
      chemotherapeutic agents commonly used in colorectal carcinoma (CRC) therapy, as
      well as to investigate the effect of cinnamaldehyde on chemotherapeutic
      associated gene expression. The synergistic interaction of cinnamaldehyde and
      chemotherapeutic agents on human CRC HT-29 and LoVo cells was evaluated using the
      combination index (CI) method. The double staining with Annexin V conjugated to
      fluorescein-isothiocyanate and phosphatidylserine was employed for apoptosis
      detection. The expression of drug-metabolizing genes, including excision repair
      cross-complementing 1 (ERCC1), orotate phosphoribosyltransferase (OPRT),
      thymidylate synthase (TS), breast cancer susceptibility gene 1 (BRCA1) and
      topoisomerase 1 (TOPO1), all in HT-29 and LoVo cells, with or without the
      addition of cinnamaldehyde, was examined by quantitative polymerase chain
      reaction (PCR). Cinnamaldehyde had a synergistic effect on the chemotherapeutic
      agents cytotoxicity in HT-29 and LoVo cells. In addition, cinnamaldehyde
      suppressed BRCA1, TOPO1, ERCC1 and TS mRNA expression, except for OPRT
      expression, which was markedly upregulated. Our findings indicate that
      cinnamaldehyde appears to be a promising candidate as an adjuvant in combination
      therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic
      agents used in CRC treatment. The possible mechanisms of its action may involve
      the regulation of drug-metabolizing genes.

PMID- 24276480
TI  - Efficient hybridization between Lycopersicon esculentum and L. peruvianum via
      embryo callus.
AB  - Embryo callus was produced in up to 12% of the undeveloped seeds of the
      interspecific cross L. esculentum cv. VFNT cherry x L. peruvianum LA1283-4, a
      cross which does not produce viable seeds. Plants were produced from 90% of those
      callus clones by regeneration and rooting. Evidence that these plants were hybrid
      includes morphology, isoenzyme patterns and fertility relations. Both diploid and
      tetraploid plants were produced, 40% of the regenerated callus clones producing
      at least one diploid plant. Thus, up to 4% of the undeveloped seeds plated for
      callus production eventually yielded diploid hybrid plants. In contrast, among
      401 undeveloped seeds dissected, no embryos suitable for embryo culture were
      found. A backcross of the embryo callus hybrids to the L. esculentum parent has
      succeeded - producing, as expected, only undeveloped seeds; these undeveloped
      seeds have produced callus. 

PMID- 24276479
TI  - Cytogenetics of synaptic mutants in higher plants.

PMID- 24276481
TI  - Suppression of multivalent formation by B chromosomes in natural and artificial
      autopolyploids of scurvy-grass (Cochlearia L.).
AB  - In diploid Cochlearia pyrenaica, its established natural autotetraploid C.
      officinalis, and their newly induced autotetraploid and auto-octoploid
      derivatives, B chromosomes change the normal pattern of chromosome association by
      suppressing homologous pairing. Frequency of bivalents increases at the expense
      of multivalents from lower to higher numbers of B chromosomes. The reduction of
      multivalents due to the direct influence of the B chromosomes, independent of
      pollen mother cell chiasma frequency, is suggested as being related to the
      mechanism that prevents A/B chromosome pairing. 

PMID- 24276482
TI  - Effects of chromosome reconstruction on deletion clustering in Hordeum vulgare.
AB  - The barley standard karyotype, two reconstructed karyotypes with all chromosomes
      interdistinguishable, and four translocation lines were treated with maleic
      hydrazide. A specific chromosomal site in satellite chromosome 7 (segment 44
      adjacent to the nucleolus organizer region) of the standard karyotype was found
      to represent a deletion hot spot. A sample of specifically reconstructed
      karyotypes were used to check whether or not transposition of the hot spot
      region, or changes of its neighborhood, would affect its involvement in
      deletions. One of the seven karyotypes (translocation line T 505 with a pair of
      chromosomes having both nucleolus organizer regions and satellites in opposite
      arms) was without deletion clustering in segment 44. At the same time, a
      prominent Giemsa band close to the secondary constriction was absent from segment
      44. These data show that the involvement in deletions of a certain chromosome
      segment is modifiable in certain cases by chromosome reconstruction. Similar
      observations have been made in Vicia faba. 

PMID- 24276483
TI  - Electrophoretic analysis of sucrose synthetase proteins in the complementing
      heterozygotes at the Shrunken locus in maize.
AB  - Electrophoretic comparisons of sucrose synthetase (SS) proteins in complementing
      heterozygotes and the corresponding in vitro mixtures of extracts from the
      homozygotes are described. The latter revealed two protein bands in the expected
      fashion. The SS protein pattern in the hybrid was different from that of the
      mixtures. The possibility of heteromeric SS molecules, formed by random
      polymerization of subunits of the tetramer coded by each allele in the
      heterozygote, was considered. Such an interaction was expected to form a multiple
      of five SS proteins that could be visualized after gel electrophoresis. However,
      only two SS bands were seen in the hybrids. The basis of this marked deviation
      remains to be explained. 

PMID- 24276484
TI  - Low temperature effect on selective fertilization by pollen mixtures of wild and
      cultivated tomato species.
AB  - In vitro pollen germination of cultivated tomato, Lycopersicon esculentum Mill.,
      is inhibited by an ambient temperature of 5 degrees C, more so than pollen from a
      Peruvian ecotype of Lycopersicon hirsutum Humb. & Bonpl. originating from an
      altitude of 3200 m. The frequency of L. hirsutum gametes contributing to hybrid
      zygote formation is more than doubled when controlled fertilizations with pollen
      mixtures of the two species occurs at 12/6 degrees C as compared to crosses with
      the same mixtures at 24/19 degrees C. The results suggest that differential
      selection at the gametophytic level occurs in response to low temperature
      regimes. To our knowledge this is the first time in higher plants that alteration
      of an environmental factor has been demonstrated to change selection values of
      male gametophytes in a fashion predicted by the ecology of the parental
      sporophytes. 

PMID- 24276485
TI  - Studies on maternal inheritance in polyploid wheats with cytoplasmic DNAs as
      genetic markers.
AB  - Restriction fragment patterns of DNA fragments obtained after EcoRI cleavage of
      chloroplastic (cp) and mitochondrial (mt) DNAs isolated from different wheat
      species were compared. T. aestivum, T. timopheevi, Ae. speltoides, Ae.
      sharonensis and T. urartu gave species specific mt DNA patterns. Consequently,
      the cytoplasmic genomes of wheat cannot have originated from contemporary Ae.
      speltoides, Ae. sharonensis and T. urartu species. It is shown that cp and mt
      DNAs of Ae. ventricosa, a tetraploid used to transfer eyespot resistance into T.
      aestivum, contains cp and mt DNAs differing from DNAs isolated from T. aestivum
      and other wheats. In contrast, the cytoplasmic DNAs of Ae. ventricosa and Ae.
      squarrosa reveal an important homology, suggesting that Ae. squarrosa was the
      female parent of Ae. ventricosa. Disomic addition lines (T. aestivum - Ae.
      ventricosa) in both Ae. ventricosa cytoplasm and T. aestivum cytoplasm contained
      cytoplasmic DNAs identical to those of the maternal parent. Restriction patterns
      of the cp and mt DNAs isolated from eight lines of Triticale differing in their
      cytoplasm have been compared to those of the maternal parent. A strict maternal
      inheritance has been observed in each case. 

PMID- 24276486
TI  - Single tester triple test cross analysis in spring wheat.
AB  - Two experiments, each including the same 30 homozygous varieties of spring wheat
      plus one separate tester variety, were conducted in order to detect epistasis and
      to test and estimate the additive and dominance components of genetic variation
      for five quantitative traits: final plant height, spike length, number of
      spikelets per spike, 100-kernel weight and grain yield per plant. Epistasis
      played a significant role in the control of 100-kernel weight and yield per
      plant. There was a gratifyingly good agreement between the two independent
      methods (2-B1i - -f1i - -Pi and 2-Bci - -F1i) used to test the presence of
      epistasis. In both experiments, there was a remarkably uniform high dominance
      ratio for most of the traits studied indicating that this test cross design is
      equally sensitive to both additive and dominance genetic variation. 

PMID- 24276487
TI  - Forging links between population and quantitative genetics.
AB  - An initially rare allele with a large effect on a quantitative character is
      expected to exhibit the following behaviour in artificial selection lines: 1. It
      should change in frequency, or be lost by chance, at rates predictable from the
      effects of the allele on the quantitative character and the selection regime
      imposed. 2. At the phenotypic level the behaviour of the allele should cause (a)
      asymmetrical responses to bidirectional selection, (b) variation among replicate
      lines in response to selection corresponding to the behaviour of the allele in
      individual lines, (c) changes in heritability in lines in which the allele
      increases in frequency and (d) selection response compatible with the effects of
      the allele. This paper reports an experimental evaluation of these predictions
      utilizing a rare allele of large effect (sm (lab) ) detected in a sample of the
      Canberra outbred population of Drosophila melanogaster at a frequency of 1/120.
      Homosygosity for this allele reduced abdominal bristle number by more than 50%,
      altered the abdominal bristle pattern and reversed the sexual dimorphism for
      abdominal bristle number. Experiments were done to characterise sm (lab) and all
      evidence indicates that it is a single allele with a very large
      effect.Bidirectional selection for abdominal bristle number was carried out in
      three high and three low lines from this sample of the Canberra population. The
      sm (lab) allele rose in frequency and went to fixation in two of the low lines
      (in 10 generations) but was lost from the third. These times to fixation were
      slower than the expectations derived from computer simulations of the behaviour
      of such an allele but this can be attributed to the lower fitness of sm (lab)
      homozygotes. The proportions of lines with the allele fixed or lost were
      compatible with expectations. At the phenotypic level, the behavior of sm (lab)
      had the expected consequences, namely, (i) asymmetrical responses to
      bidirectional selection, (ii) variation in response among replicate low lines
      corresponding to the behaviour of sm (lab) , (iii) changes in heritabilities in
      the lines in which sm (lab) went to fixation, and (iv) selection responses
      compatible with the effects of the allele.A test for rare alleles of large effect
      was proposed, based on the expected pattern of change in heritability under
      artificial selection. This test was applied to the high selection lines but no
      evidence was found for important effects due to rare alleles of large effect
      increasing abdominal bristle number, a conclusion consistent with other
      independent evidence.This work provides experimental corroboration of the links
      between population genetics and quantitative genetics. 

PMID- 24276488
TI  - Axial binding and host-guest interactions of a phthalocyanine resorcinarene
      cavitand hybrid.
AB  - A Zn phthalocyanine-resorcinarene cavitand hybrid was prepared. The axial binding
      and host-guest interactions of this hybrid with a pyridinyl-pyrene were
      investigated by UV-vis and fluorescence spectroscopic means, revealing the
      encapsulation of the guest maintained by axial coordination to the Zn
      phthalocyanine. Energy transfer between the pyrene and the phthalocyanine was
      evidenced. 

PMID- 24276490
TI  - Femtosecond to nanosecond dynamics of 2,2'-bipyridine-3,3'-diol inside the nano
      cavities of molecular containers.
AB  - Femtosecond fluorescence upconversion measurements are employed to elucidate the
      mechanism of ultrafast double proton transfer dynamics of BP(OH)2 inside
      molecular containers (cucurbit[7]uril (CB7) and beta-cyclodextrin (beta-CD)).
      Femtosecond up-converted signals of BP(OH)2 in water consist of growth followed
      by a long decay component (~650 ps). The appearance of the growth component (~35
      ps) in the up-converted signal indicates the presence of a two-step sequential
      proton transfer process of BP(OH)2 in water. Surprisingly, the up-converted
      signal of BP(OH)2 inside the CB7 nano-cavity does not exhibit any growth
      component characteristic of a two-step sequential process. Interestingly, the
      growth component exists inside the nano-cavity of beta-CD (having similar cavity
      size as that of CB7), inferring the presence of a two-step sequential process of
      PT inside the beta-CD nano-cavity. The different features of PT dynamics of
      BP(OH)2 in the above mentioned two macrocyclic hosts may be attributed to the
      presence and absence of water solvation network surrounding the BP(OH)2 inside
      the nano-cavities of beta-CD and CB7, respectively. Finally, docking and DFT
      calculations have been employed in deciphering the molecular pictures of the
      interactions between BP(OH)2 and the macrocyclic host.

PMID- 24276489
TI  - Post-mortem computed tomography ventilation; simulating breath holding.
AB  - Whilst the literature continues to report on advances in the use of post-mortem
      computed tomography (PMCT), particularly in relation to post-mortem angiography,
      there are few papers published that address the diagnostic problems related to
      post-mortem changes in the lungs and ventilation. We present a development of
      previous methods to achieve ventilated PMCT (VPMCT). We successfully introduced a
      supraglottic airway in 17/18 cases without causing overt damage, despite rigor
      mortis. Using a clinical portable ventilator, we delivered continuous positive
      airway pressure to mimic clinical breath-hold inspiratory scans. This caused
      significant lung expansion and a reduction in lung density and visible normal
      post-mortem changes. All thoracic pathology identified at autopsy, including
      pneumonia, was diagnosed on VPMCT in this small series. This technique provides a
      rapid form of VPMCT, which can be used in both permanent and temporary
      mortuaries, allowing for the post-mortem radiological comparison of pre
      ventilation and post-ventilation images mimicking expiratory and inspiratory
      phases. We believe that it will enhance the diagnostic ability of PMCT in
      relation to lung pathology. 

PMID- 24276491
TI  - Summaries for patients. Screening for oral cancer: U.S. Preventive Services Task
      Force recommendation statement.

PMID- 24276492
TI  - Evaluation of gastroenterology and hepatology articles on Wikipedia: are they
      suitable as learning resources for medical students?
AB  - BACKGROUND: With the changes introduced to medical curricula, medical students
      use learning resources on the Internet such as Wikipedia. However, the
      credibility of the medical content of Wikipedia has been questioned and there is
      no evidence to respond to these concerns. The aim of this paper was to critically
      evaluate the accuracy and reliability of the gastroenterology and hepatology
      information that medical students retrieve from Wikipedia. METHODS: The Wikipedia
      website was searched for articles on gastroenterology and hepatology on 28 May
      2013. Copies of these articles were evaluated by three assessors independently
      using an appraisal form modified from the DISCERN instrument. The articles were
      scored for accuracy of content, readability, frequency of updating, and quality
      of references. RESULTS: A total of 39 articles were evaluated. Although the
      articles appeared to be well cited and reviewed regularly, several problems were
      identified with regard to depth of discussion of mechanisms and pathogenesis of
      diseases, as well as poor elaboration on different investigations. Analysis of
      the content showed a score ranging from 15.6+/-0.6 to 43.6+/-3.2 (mean+/-SD). The
      total number of references in all articles was 1233, and the number of references
      varied from 4 to 144 (mean+/-SD, 31.6+/-27.3). The number of citations from peer
      reviewed journals published in the last 5 years was 242 (28%); however, several
      problems were identified in the list of references and citations made. The
      readability of articles was in the range of -8.0+/-55.7 to 44.4+/-1.4; for all
      articles the readability was 26+/-9.0 (mean+/-SD). The concordance between the
      assessors on applying the criteria had mean kappa scores in the range of 0.61 to
      0.79. CONCLUSION: Wikipedia is not a reliable source of information for medical
      students searching for gastroenterology and hepatology articles. Several
      limitations, deficiencies, and scientific errors have been identified in the
      articles examined.

PMID- 24276493
TI  - Persistence of chlorantraniliprole granule formulation in sugarcane field soil.
AB  - Chlorantraniliprole, an anthranilic diamide insecticide with novel mode of
      action, is found effective against several lepidopteran as well as coleopteran,
      dipteran, and hemipteran pests. The present studies were carried out to study the
      persistence pattern of chlorantraniliprole on sugarcane field soil following
      application of granule formulation. The residues of chlorantraniliprole were
      estimated using high performance liquid chromatograph (HPLC) and confirmed by
      liquid chromatograph-mass spectrometry (LC-MS/MS). Following application of
      chlorantraniliprole (Ferterra 0.4G) at 100 and 200 g a.i. ha(-1), the average
      initial deposits of chlorantraniliprole were observed to be 0.88 and 1.59 mg kg(
      1), respectively. These residues dissipated below the limit of quantification
      (LOQ) of 0.01 mg kg(-1) after 56 days of the application of insecticides at both
      the dosages. The half-life values (t 1/2) of chlorantraniliprole were worked out
      to be 8.36 and 8.25 days, at recommended and double the recommended dosages,
      respectively.

PMID- 24276494
TI  - Physicochemical properties of seeds of Capparis species growing wild in Turkey.
AB  - While Capparis spinosa var. herbaceace (2009) seeds collected from the Mardin
      midyat region contains the highest protein (22.25%), C. spinosa var. spinosa
      seeds (2009) collected from the Mugla-Milas region contained the lowest protein
      (18.25%). In addition, oil contents of C. spinosa and Capparis ovata seeds
      changed between 27.74 to 31.09 and 28.66 to 31.40%, respectively. Crude cellulose
      contents of C. spinosa and C. ovata seeds were found as 28.24 and 29.67%,
      respectively. It was found that ash content of C. spinosa and C. ovata seeds were
      found between 2.13 and 2.23%, respectively. Phenolic matter content of C. spinosa
      and C. ovata were found between 1.98 mg (GAE) and 1.76 mg (GAE), respectively.
      Radical activity values of C. spinosa and C. ovata were determined as 83.432 and
      83.718%, respectively.

PMID- 24276495
TI  - Genetic absence of the vesicular inhibitory amino acid transporter differentially
      regulates respiratory and locomotor motor neuron development.
AB  - During mid to late embryonic development (E13 to birth in mice), the neuromotor
      system is refined by reducing motor neuron (MN) numbers and establishing nascent
      synaptic connections onto and by MNs. Concurrently, the response to GABAergic and
      glycinergic synaptic activity switches from postsynaptic excitation to
      inhibition. Our previous studies on mutant mice lacking glycinergic transmission
      or deficient in GABA suggests that altered MN activity levels during this
      developmental period differentially regulates MN survival and muscle innervation
      for respiratory and non-respiratory motor pools. To determine if combined loss of
      GABAergic and glycinergic transmission plays a similar or exaggerated role, we
      quantified MN number and muscle innervation in two respiratory (hypoglossal and
      phrenic) and two locomotor (brachial and lumbar) motor pools, in mice lacking
      vesicular inhibitory amino acid transporter, which display absent or severely
      impaired GABAergic and glycinergic neurotransmission. For respiratory MNs, we
      observed significant decreases in MN number (-20 % hypoglossal and -36 % phrenic)
      and diaphragm axonal branching (-60 %). By contrast, for non-respiratory brachial
      and lumbar MNs, we observed increases in MN number (+62 % brachial and +84 %
      lumbar) and axonal branching for innervated muscles (+123 % latissimus dorsi for
      brachial and +61 % gluteal for lumbar). These results show that combined absence
      of GABAergic and glycinergic neurotransmission causes distinct regional changes
      in MN number and muscle innervation, which are dependent upon the motor function
      of the specific motor pool.

PMID- 24276496
TI  - Feeding preferences of eastern spruce budworm larvae in two-choice tests with
      extracts of mature foliage and with pure amino acids.
AB  - The feeding preferences and feeding rates of eastern spruce budworm on extracts
      from mature foliage normally avoided by larvae indicate that the chemical
      composition of four major host plants does not account for this avoidance. Other
      factors such as the degree of lignification and/or moisture content of the older
      foliage may play a more important role. Of 14 amino acids tested, alanine,
      lysine, proline, and serine stimulated feeding. The interactions of amino acids
      and sucrose were studied, and the results are discussed in relation to feeding
      preferences and feeding rates. 

PMID- 24276497
TI  - Chemical protection of pheromones containing an internal conjugated diene system
      from isomerization and oxidation.
AB  - Conjugated diene systems are common in natural products, including pheromones.
      The systems are sensitive to heat, light, and oxygen, among other things. They
      can be protected by antioxidants and UV absorbers, which slow downcis-trans
      isomerization and oxidation. Three sex pheromones (one as an analog)
      containingZ,E, E,Z, andE,E units were studied: (Z,E)-9,11-C14OAc, (E,Z)-7,9
      C12OAc, and (E,E)-10,12-C16OAc. The UV absorber 2-hydroxy-4-methoxybenzophenone
      and the antioxidants BHT and BHA were found to be effective in solution. The
      protective effect of the UV absorber against photoisomerization on paper carriers
      was not as good as that in solution. Preliminary studies on the utilization of
      formulations containing these compounds and (Z,E)-9,11-C14OAc in the mass
      trapping of Egyptian cotton leafworm male in cotton fields showed the new
      combinations to be as good as a previously used formulation with UOP 688, a
      compound which is unpleasant to handle. 

PMID- 24276498
TI  - Trirhabda canadensis (Coleoptera: Chrysomelidae) responses to plant odors.
AB  - The responses of the goldenrod leaf beetleTrirhabda canadensis to host and
      nonhost volatile odors were tested in a Y-tube olfactometer in the laboratory.
      Beetles preferred host to nonhost odors and were sensitive to concentrations of
      host odor. Beetles distinguished between host and nonhost volatiles of only one
      of the two nonhostSolidago species; host volatiles were preferred to all nonhost
      volatiles at the family and order levels. In other words, all nonhosts above the
      genus level had similar effects on beetle responses. Although the odors of most
      nonhosts were neutral (i.e., neither attractive nor repellent) to the beetles as
      tested against air, this neutrality disappeared if the odors of two or more
      nonhosts were added to the host odor and beetles were given a choice between this
      mixture and pure host odor. Given this choice, they strongly preferred pure host
      odor, which suggests that diversity of odors per se is unattractive to the
      beetles. Beetles walked rather than flew to locate their hosts in the field, and
      their movements suggest that they used olfactory cues to locate hosts. 

PMID- 24276499
TI  - Chemosensory responses in two species of elephants to constituents of temporal
      gland secretion and musth urine.
AB  - This report discusses three areas of investigation: (1) The chemical components
      in the temporal gland secretion (TGS) of Asian (Elephas maximus) and African
      (Loxodonta africana) elephants were characterized by radioimmunoassay (RIA) for
      testosterone (T) and dihydrotestosterone (DHT) levels and by on-column capillary
      column gas chromatographic analysis of volatiles. An inverse relationship between
      TGS testosterone levels and (E)-farnesol levels was observed. (2). African
      elephants responded preferentially toward a particular constituent of African
      elephant TGS. (3) Urine from Asian bull elephants in musth was partially
      fractionated by high-performance liquid chromatography. Specific chromatographic
      regions elicited dramatic avoidance responses from female African elephants.
      These results support the suggestion that the TGS plays multiple
      chemocommunicative roles. 

PMID- 24276500
TI  - Ponatinib (Inclusig) marketing and sales suspended.

PMID- 24276501
TI  - Vortioxetine (Brintellix) for depression.

PMID- 24276502
TI  - Hydrocodone/chlorpheniramine (Vituz).

PMID- 24276503
TI  - Ezogabine (Potiga) toxicity.

PMID- 24276504
TI  - Perioperative cardiac complications and 30-day mortality in patients undergoing
      intracranial aneurysmal surgery with adenosine-induced flow arrest: a
      retrospective comparative study.
AB  - BACKGROUND: Adenosine-induced flow arrest is a technique used to assist in the
      surgical clipping of complex aneurysms. OBJECTIVE: To assess the safety
      associated with adenosine-assisted intracranial aneurysm surgery. METHODS:
      Medical records of all patients presenting between January 1, 2009, and December
      31, 2012, for intracranial aneurysm surgery were analyzed. Patients were divided
      into 2 groups based on the intraoperative administration of adenosine: the
      nonadenosine group (n = 262) and the adenosine group (n = 64). The primary
      outcome compared between groups included a composite of 30-day mortality and
      incidences of perioperative cardiac complications (perioperative myocardial
      infarction or perioperative cardiac arrhythmias). RESULTS: The study groups were
      statistically similar except for a difference in the size and location of
      cerebral aneurysms and the incidence of coronary artery disease. The primary
      composite outcome occurred in 4.6% and 9.4% of patients in the nonadenosine and
      adenosine groups, respectively (P = .13). After adjustment for differences in the
      incidence of coronary artery disease between the 2 groups, the odds of the
      primary outcome were not significantly different between the groups (adjusted
      odds ratio = 2.12; 95% confidence interval, 0.76-5.93; P = .15). There were also
      no significant differences in the durations of hospital and intensive care unit
      stay between the study groups. CONCLUSION: Our results suggest that adenosine
      assisted intracranial aneurysm surgery is not associated with an increase in
      perioperative cardiac complications or mortality in patients with low risk of
      coronary artery disease and may be considered a safe technique to assist clipping
      of complex aneurysms.

PMID- 24276505
TI  - The neurological emergency room and prehospital stroke alert: the whole is
      greater than the sum of its parts.
AB  - BACKGROUND: Emergency medical services (EMS) prenotification to hospitals
      regarding the arrival of patients who have had a stroke is recommended to
      facilitate the workup once the patient arrives. Most hospitals have the patient
      enter the emergency department (ED) before obtaining a head computed tomography
      (CT) scan. At Capital Health, prehospital stroke-alert patients are delivered
      directly to CT and met by a neurological emergency team. The goal of bypassing
      the ED is to reduce the time to treatment. OBJECTIVE: To evaluate (1) door-to-CT
      and door-to-needle time in patients with an acute stroke who arrive as
      prehospital stroke alerts and (2) the accuracy of EMS assessment. METHODS: A
      prospective database of all prehospital stroke alert patients was kept and data
      retrospectively reviewed for patients who were seen between July 2012 and July
      2013. RESULTS: Between July 2012 and July 2013, 141 prehospital stroke alerts
      were called to our emergency department, and the patients were stable enough to
      bypass the ED and go directly to CT. EMS assessment of stroke was accurate 66% of
      the time, and the diagnosis was neurological 89% of the time. The average time
      between patient arrival and acquisition of CT imaging was 11.8 minutes. Twenty
      six of the 141 patients (18%) received intravenous tissue plasminogen activator.
      The median time from arrival to intravenous tissue plasminogen activator bolus
      was 44 minutes. CONCLUSION: Trained EMS responders are able to correctly identify
      patients who are experiencing neurological/neurosurgical emergencies and deliver
      patients to our comprehensive stroke center in a timely fashion after
      prenotification. The prehospital stroke alert protocol bypasses the ED, allowing
      the patient to be met in CT by the neurological ED team, which has proven to
      decrease door-to-CT and door-to-needle times from our historical means.
      ABBREVIATIONS: ASLS, Advanced Stroke Life SupportDTN, door-to-needleED, emergency
      departmentEMS, emergency medical servicesEMT, emergency medical technicianIV,
      intravenousMEND, Miami Emergency Neurological DeficitPHSA, prehospital stroke
      alerttPA, tissue plasminogen activator.

PMID- 24276506
TI  - Discovery of novel FabF ligands inspired by platensimycin by integrating
      structure-based design with diversity-oriented synthetic accessibility.
AB  - An approach for designing bioactive small molecules has been developed in which
      de novo structure-based ligand design (SBLD) was focused on regions of chemical
      space accessible using a diversity-oriented synthetic approach. The approach was
      exploited in the design and synthesis of a focused library of platensimycin
      analogues in which the complex bridged ring system was replaced with a series of
      alternative ring systems. The affinity of the resulting compounds for the C163Q
      mutant of FabF was determined using a WaterLOGSY competition binding assay.
      Several compounds had significantly improved affinity for the protein relative to
      a reference ligand. The integration of synthetic accessibility with ligand design
      enabled focus to be placed on synthetically-accessible regions of chemical space
      that were relevant to the target protein under investigation. 

PMID- 24276507
TI  - Current status of paediatric post-mortem imaging: an ESPR questionnaire-based
      survey.
AB  - BACKGROUND: The use of post-mortem imaging, including skeletal radiography, CT
      and MRI, is increasing, providing a minimally invasive alternative to
      conventional autopsy techniques. The development of clinical guidelines and
      national standards is being encouraged, particularly for cross-sectional
      techniques. OBJECTIVE: To outline the current practice of post-mortem imaging
      amongst members of the European Society of Paediatric Radiology (ESPR). MATERIALS
      AND METHODS: We e-mailed an online questionnaire of current post-mortem service
      provisions to members of the ESPR in January 2013. The survey included direct
      questions about what services were offered, the population imaged, current
      techniques used, imaging protocols, reporting experience and intended future
      involvement. RESULTS: Seventy-one percent (47/66) of centres from which surveys
      were returned reported performing some form of post-mortem imaging in children,
      of which 81 % perform radiographs, 51% CT and 38% MRI. Eighty-seven percent of
      the imaging is performed within the radiology or imaging departments, usually by
      radiographers (75%), and 89% is reported by radiologists, of which 64% is
      reported by paediatric radiologists. Overall, 72% of positive respondents have a
      standardised protocol for radiographs, but only 32% have such a protocol for CT
      and 27% for MRI. Sixty-one percent of respondents wrote that this is an important
      area that needs to be developed. CONCLUSION: Overall, the majority of centres
      provide some post-mortem imaging service, most of which is performed within an
      imaging department and reported by a paediatric radiologist. However, the
      populations imaged as well as the details of the services offered are highly
      variable among institutions and lack standardisation. We have identified people
      who would be interested in taking this work forwards.

PMID- 24276509
TI  - Somatic embryogenesis from Lycopersicon peruvianum leaf mesophyll protoplasts.
AB  - One to five percent of Lycopersicon peruvianum (L.) Mill. leaf mesophyll
      protoplasts undergo cell division and concomitant organization to form
      embryogenic-like structures when cultured in Murashige and Skoog medium (1962)
      containing 3% sucrose, 9% mannitol, 1.0 mg/l kinetin (K) and 1.0 mg/l naphthalene
      acetic acid (NAA) at pH 5.6-5.8 (medium A). These embryogenic structures, after
      passing through developmental stages similar to those observed in zygotic
      embryogeny, are capable of forming shoots on hormone-free medium A. In medium B,
      wherein 0.5 mg/l of 2,4-dichlorophenoxyacetic (2,4-D) replaced the hormones (K
      and NAA), embryogenic structures did not develop. However, callus originating in
      medium B retained morphogenetic capacity as was evidenced by subsequent shoot
      regeneration when they were transferred to medium A with K and NAA replaced by
      1.0 mg/l zeatin (Z). The potential value of incorporating this regeneration trait
      into Lycopersicon species and cultivated lines for use in tissue culture programs
      is discussed. 

PMID- 24276508
TI  - Limited genetic diversity in the critically endangered Mexican howler monkey
      (Alouatta palliata mexicana) in the Selva Zoque, Mexico.
AB  - The Mexican howler monkey (Alouatta palliata mexicana) is a critically endangered
      primate, which is paleoendemic to Mexico. However, despite the potential
      significance of genetic data for its management and conservation, there have been
      no population genetic studies of this subspecies. To examine genetic diversity in
      the key remaining forest refuge for A. p. mexicana, the Selva Zoque, we amplified
      full-length mitochondrial control region sequences (1,100 bp) from 45 individuals
      and found 7 very similar haplotypes. Haplotype diversity (h = 0.486) and
      nucleotide diversity (pi = 0.0007) were extremely low compared to other
      Neotropical primates. Neutrality tests, used to evaluate demographic effects
      (Tajima's D = -1.48, p = 0.05; Fu's F s = -3.33, p = 0.02), and mismatch
      distribution (sum of squares deviation = 0.006, p = 0.38; raggedness index =
      0.12, p = 0.33) were consistent with a recent and mild population expansion and
      genetic diversity appears to be historically low in this taxon. Future studies
      should use a combination of mitochondrial and nuclear markers to fully evaluate
      genetic diversity and to better understand demographic history in A. p. mexicana.
      These studies should be undertaken throughout its geographic range in order to
      evaluate population structure and identify management units for conservation. Due
      to the limited distribution and population size of A. p. mexicana, future
      conservation strategies may need to consider genetic management. However, a more
      detailed knowledge of the population genetics of the subspecies is urgently
      recommended to maximise the conservation impact of these strategies.

PMID- 24276510
TI  - Somatic embryogenesis and plant regeneration from leaf tissues and anthers of
      Pennisetum purpureum Schum.
AB  - Expiants obtained from leaves of Pennisetum purpureum Schum. gave rise to callus
      tissues when cultured on Murashige and Skoog's nutrient medium containing only
      2,4-dichlorophenoxyacetic acid (2,4-D), or 2,4-D supplemented with naphthalene
      acetic acid and/or 6-benzylaminopurine. Embryoids were formed in the white,
      compact and highly organised areas of the callus and developed into plants.
      Histological examination of cultured leaf segments showed that the callus tissue
      was formed by division in cells of the mesophyll tissue as well as the lower
      epidermis. A rapidly growing embryogenic callus tissue was also obtained
      apparently from the somatic tissues of anthers of P. purpureum, and induced to
      form plants through somatic embryogenesis. Plants obtained from leaf and anther
      culture were grown to maturity, and were shown to have the normal chromosome
      number of 2n = 4x = 28. 

PMID- 24276511
TI  - Somatic embryogenesis and plant regeneration from leaf tissues of Panicum maximum
      Jacq.
AB  - Somatic embryogenesis was induced in proliferating leaf segments of Panicum
      maximum Jacq., cultured on Murashige and Skoog's nutrient medium containing 2,4
      dichlorophenoxyacetic acid and coconut milk. The embryoids gave rise to plants on
      a medium containing gibberellic acid. The plants were successfully transplanted
      to soil and grown to maturity. Histological examination of proliferating leaves
      showed that the embryogenic callus tissue was formed by divisions in cells of the
      lower epidermis as well as the mesophyll tissue. The regenerated plants showed
      the normal chromosome number of 2n=4x=32. 

PMID- 24276512
TI  - Restriction endonuclease cleavage site map of chloroplast DNA from Oenothera
      parviflora (Euoenothera plastome IV).
AB  - 1) More than 50 cleavage sites produced by the restriction endonucleases Sal I,
      Pst I, Kpn I, Sma I and Eco RI have been physically mapped on the 47 MUm circular
      DNA molecule of the Euoenothera plastome IV. This plastome (= plastid genome) is
      considered to be the phylogenetically oldest of the subsection. 2) The DNA
      molecule is segmentally organized into four regions represented by a large
      duplicated sequence in inverted orientation whose copies are separated by two
      single-copy segments. The single-copy regions comprise about 14 and 57 Md in
      size, respectively. 3) The size of the inverted repeat, about 15 Md, was
      determined by restriction site mapping, by mapping of genes for ribosomal RNAs
      and by hybridization of a cRNA transcribed from a homologous part of Spinacia
      oleracea chloroplast DNA which appears to be phylogenetically conserved. 4)
      Hybridization of radio-iodinated spinach 16S, 23S and 5S chloroplast rRNA species
      to Southern blots of restricted plastome IV DNA has localized the rDNA to the
      inverted repeat regions, in the order given. The genes for 16S and 23S rRNA are
      separated by a 2.4 kbp spacer. 5) The physical map of the plastome IV DNA serves
      as basis for comparison with the DNA from the four other, closely related
      Euoenothera plastomes. 

PMID- 24276513
TI  - Peculiarities in PMC Meiosis of Pisum sativum.
AB  - The general outline of meiotic prophase proposed by Wilson in 1925 included three
      stages which usually are missing in the description of meiosis today: (1)
      synizesis (= the synaptic stage in plants), (2) the diffuse stage, which follows
      the pachytene and (3) the second contraction, following the diffuse stage. The
      last two stages were regarded by Wilson as being very variable and could even be
      lacking. These stages, described by early plant cytologists later became regarded
      as fixation artefacts and after the introduction of the squash technique were
      either misinterpreted and/or forgotten.However, all three stages are easily
      recognised in aceticethanol fixed preparations of plant meiosis and are
      demonstrated in Pisum sativum meiosis. Pisum meiosis differs from the usual plant
      meiosis by: (1) the peculiar timing of the late prophase, (2) the existence of
      extrachromosomal fibrillar structures appearing at synizesis and staining by
      Feulgen - Light Green, and (3) the appearance of multiple nucleoli in the late
      prophase. The possibility that these nucleoli and fibrillar structures are of
      relevance in relation to gene amplification is discussed. 

PMID- 24276514
TI  - Cytogenetic studies on the F1 hybrid Solanum indicum x S. torvum.
AB  - The F1 hybrid Solanum indicum x S. torvum could be maintained only under special
      conditions. Meiosis was highly irregular: about 45% of chromosomes remained as
      univalents and wherever pairing was observed, it appeared to be loose. A maximum
      number of three higher chromosome associations other than bivalents, including
      'Y' and 'spoon' type associations, indicate extensive chromosome repatterning.
      Occasional occurrence of twelve bivalents per PMC suggests that, notwithstanding
      the extreme divergence, the species have retained sufficient ancestral chromosome
      homoeologies. Chromosome distribution at anaphase-I was highly irregular and
      precocious division of chromosomes was observed frequently. This hybrid was 100%
      sterile and the dropping off of immature flower buds was observed. 

PMID- 24276515
TI  - Translocations induced by fast neutrons and X-rays in Delia antiqua.
AB  - A comparison was made using X-rays and fast neutrons for the induction of
      translocations in Delia antiqua. Using the same radiation dose, no difference in
      efficiency between the two radiation types could be observed. However, with fast
      neutrons many multiple translocations were induced, including a quadruple
      translocation involving 4 out of 5 autosomes. One male linked translocation was
      also induced.The reciprocal translocations were assigned into two classes:
      symmetrical and asymmetrical, and ten of the latter were chosen for inbreeding to
      produce homozygotes. Asymmetrical exchanges were chosen so that translocation
      homozygotes could be differentiated cytologically from the normal karyotype. In
      seven different translocations, homozygous larvae were observed, but often at a
      low frequency. In four of these lines, viable adult homozygotes were observed.
      Subsequent random sib-crossing failed to produce a homozygous line. 

PMID- 24276516
TI  - Monosomic analysis of genes for resistance against stem rust races in bread
      wheat.
AB  - Using monosomic analysis genes governing resistance in one wheat variety,
      'E5883', against stem rust races 15C and 122, were located on specific
      chromosomes. Against race 15C, a major dominant gene, Sr6, was located on
      chromosome 2D of 'E5883' with minor modifiers found on chromosomes 4A and 6D.
      Against race 122, the presence of a recessive hemizygous ineffective gene, Sr8,
      was identified, located on chromosome 6A of variety 'E5883'. 

PMID- 24276517
TI  - Analysing environments for plant breeding purposes as exemplified by multivariate
      analyses of long term wheat yields.
AB  - A previous attempt to relate long term yields from the Western Australian wheat
      belt to climatic factors proved only partially successful. Here, principal
      component analysis has been used to examine the patterns of variability created
      by those socio-economic factors which may have obscured any underlying
      relationship which existed between yield and climate. In fact, these analyses
      revealed the existence of variation peculiar to particular groups of years, a
      result which could explain why many attempts to relate crop yields directly to
      climatic factors have proved unsuccessful. The plant breeding implications of
      these genotype x environment interactions are considered. 

PMID- 24276518
TI  - A note on the island model with sex dependent migration.
AB  - A theoretical calculation is presented which extends Wright's island model of
      drift and migration to differential migration between the two sexes. In this
      circumstance, local demes no longer have Hardy-Weinberg frequencies. There may be
      local heterozygote excess or deficiency depending, respectively, on whether
      migration occurs before or after mating. The magnitude of the local departure
      from Hardy-Weinberg is directly proportional to the difference between the
      migration parameters of the two sexes. These results could have important
      implications for studies where genetic markers are used for inferring population
      structure. An example from a study of Marmot colonies is cited. 

PMID- 24276519
TI  - Ferroelectric polymer networks with high energy density and improved discharged
      efficiency for dielectric energy storage.
AB  - Ferroelectric polymers are being actively explored as dielectric materials for
      electrical energy storage applications. However, their high dielectric constants
      and outstanding energy densities are accompanied by large dielectric loss due to
      ferroelectric hysteresis and electrical conduction, resulting in poor charge
      discharge efficiencies under high electric fields. To address this long-standing
      problem, here we report the ferroelectric polymer networks exhibiting
      significantly reduced dielectric loss, superior polarization and greatly improved
      breakdown strength and reliability, while maintaining their fast discharge
      capability at a rate of microseconds. These concurrent improvements lead to
      unprecedented charge-discharge efficiencies and large values of the discharged
      energy density and also enable the operation of the ferroelectric polymers at
      elevated temperatures, which clearly outperforms the melt-extruded ferroelectric
      polymer films that represents the state of the art in dielectric polymers. The
      simplicity and scalability of the described method further suggest their
      potential for high energy density capacitors. 

PMID- 24276520
TI  - Two-year follow-up after chelating therapy in a patient with adult-onset
      parkinsonism and hypermanganesaemia due to SLC30A10 mutations.

PMID- 24276521
TI  - Unusual natalizumab-associated progressive multifocal leukoencephalopathy
      starting in the brainstem.

PMID- 24276523
TI  - Molecular tectonics: homochiral coordination networks based on combinations of a
      chiral neutral tecton with Hg(II), Cu(II) or Ni(II) neutral complexes as
      metallatectons.
AB  - The use of compound 1 as an enantiomerically pure neutral and rigid organic
      linear tecton bearing two divergently oriented monodentate coordinating sites
      appended with two chiral centres of the same (S) configuration leads, in the
      presence of neutral metal complexes behaving either as a linear (Cu(hfac)2,
      Cu(OAc)2) or a V-shaped (HgCl2) 2-connecting node or a 4-connecting square node
      (NiCl2), to the formation of four homochiral 1- and 2-D coordination polymers.

PMID- 24276522
TI  - Long-term outcome after aneurysmal subarachnoid hemorrhage-risks of vascular
      events, death from cancer and all-cause death.
AB  - Smoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage
      (aSAH), but also for other cardiovascular diseases and cancer. Few prospective
      data are available on the very long term risks of vascular diseases and vascular,
      cancer-related and overall death after aSAH. We determined vascular events and
      survival status in 1,765 patients with aSAH admitted to our center from 1985 to
      2010. Cumulative risks were estimated with survival analysis. We compared risks
      of vascular, cancer-related and all-cause death with the general population with
      standardized mortality ratios (SMRs). Incidences of vascular events and death
      were compared with those after TIA/minor stroke. Conditional on surviving 3
      months after aSAH, the risk of death was 8.7 % (95 % CI 7.3-10.1) within 5 years,
      17.9 % (16.1-19.9) within 10 years, 29.5 % (27.3-31.8) within 15 years, and 43.6
      % (41.2-46.1) within 20 years after SAH. The SMR for all-cause death was 1.8 (1.6
      2.1), for vascular death 2.0 (95 % CI 1.6-2.5) and for cancer-related death 1.2
      (0.9-1.5; sensitivity analysis 1.4; 95 % CI 1.1-1.8). The increased SMR for all
      cause death persevered up to 20 years after aSAH. Compared with TIA/minor stroke
      patients, the age- and sex-adjusted cumulative incidence on vascular events was
      lower for aSAH patients [hazard ratio (HR) 0.48; 95 % CI 0.40-0.57); the HR for
      all-cause death was 0.96 (95 % CI 0.84-1.10). After aSAH, risks of vascular
      events and death, and probably also that of cancer-related death, are higher than
      in the general population. Although the long-term risk of vascular events was
      lower in aSAH patients than in TIA/minor stroke patients, the risk of death was
      similar. 

PMID- 24276524
TI  - An organizational schema for epidemiologic causal effects.
AB  - Epidemiologic textbooks and methodological papers define multiple causal effects.
      These causal effects can differ substantially; yet, the causal effect of interest
      is rarely specified in published epidemiologic studies perhaps because their
      distinctions are underappreciated. Here, we provide an organizational schema that
      distinguishes causal effects based on six characteristics. We use simple numeric
      examples to demonstrate the variability across effects and show why specifying
      the causal effect is necessary for an accurate intervention interpretation even
      under the simplest scenarios. The objective of our schema was to illuminate the
      distinguishing characteristics of various causal effects and clarify their
      interpretation, thus guiding epidemiologists in choosing an appropriate causal
      effect to estimate. 

PMID- 24276526
TI  - Co9S8 nanotube arrays supported on nickel foam for high-performance
      supercapacitors.
AB  - Uniform Co9S8 nanotube arrays on conductive nickel foam were successfully
      synthesized through a facile two-step hydrothermal method and were directly
      applied as the electrode for high-performance electrochemical capacitors. The
      formation of the tubular structure of Co9S8 can be attributed to the nanoscale
      Kirkendall effect. SEM and TEM images show that most of the Co9S8 nanotubes have
      hexagonal sections. The diameter of the Co9S8 nanotubes is about 120-200 nm and
      the wall thickness is of 40-60 nm. Cyclic voltammetry, galvanostatic charge
      discharge and electrochemical impedance measurements are applied to investigate
      the electrochemical performance of the Co9S8 nanotubes. The specific capacitance
      of the Co9S8 nanotubes is 1775 F g(-1) at 4 A g(-1), and 1483 F g(-1) at 24 A g(
      1), indicating the high rate capability. Also, the Co9S8 nanotubes exhibit stable
      cycling performance. 

PMID- 24276527
TI  - Breast cancer risk assessment in 8,824 women attending a family history
      evaluation and screening programme.
AB  - Accurate individualized breast cancer risk assessment is essential to provide
      risk-benefit analysis prior to initiating interventions designed to lower breast
      cancer risk and start surveillance. We have previously shown that a manual
      adaptation of Claus tables was as accurate as the Tyrer-Cuzick model and more
      accurate at predicting breast cancer than the Gail, Claus model and Ford models.
      Here we reassess the manual model with longer follow up and higher numbers of
      cancers. Calibration of the manual model was assessed using data from 8,824 women
      attending the family history evaluation and screening programme in Manchester UK,
      with a mean follow up of 9.71 years. After exclusion of 40 prevalent cancers, 406
      incident breast cancers occurred, and 385.1 were predicted (O/E = 1.05, 95 % CI
      0.95-1.16) using the manual model. Predictions were close to that of observed
      cancers in all risk categories and in all age groups, including women in their
      forties (O/E = 0.99, 95 % CI 0.83-1.16). Manual risk prediction with use of
      adjusted Claus tables and curves with modest adjustment for hormonal and
      reproductive factors was a well-calibrated approach to breast cancer risk
      estimation in a UK family history clinic.

PMID- 24276529
TI  - Behavioral responses of female Mexican fruit flies,Anastrepha ludens, to
      components of male-produced sex pheromone.
AB  - The behavioral responses of virgin female Mexican fruit flies elicited by
      components and combinations of the components of male-produced pheromone were
      measured in a laboratory wind-tunnel bioassay where test chemicals were applied
      to the undersides of some leaves on a treated tree but to none of the leaves of a
      control tree. Only treatments containing at least (Z)-3-nonenol and/or (Z,Z)-3,6
      nonadienol in combination with (S,S)-(-)-epianastrephin elicited strong
      behavioral responses. Responses included attraction to the vicinity of the
      pheromone but not to point sources, increased searching rate, changes in
      searching strategy, and agonism. The results support a model of pheromone
      component function in which components act as a unit to stimulate all behaviors
      of the pheromone-mediated behavioral repertoire. 

PMID- 24276528
TI  - Pretreatment metabolic tumor volumes to predict the short-term outcome of
      unresectable locally advanced squamous cell carcinoma of the esophagus treated
      with definitive chemoradiotherapy.
AB  - PURPOSE: The aim of the study was to investigate the predictive role of
      pretreatment metabolic tumor volume (MTV) in patients with squamous cell
      carcinoma of locally advanced esophageal cancer treated with definitive
      chemoradiotherapy. PATIENTS AND METHODS: Ninety patients received pretreatment
      with (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT, and two types of MTVs were
      measured on the basis of either a maximal standardized uptake value (SUVmax) of
      2.5 (MTV2.5) or a fixed threshold of 20% (MTV20%). Overall survival (OS) and
      disease-free survival (DFS) were examined, and independent prognosticators were
      identified by Cox regression analysis. RESULTS: On a median follow-up of 15
      months, 51 patients were seen to have died because of tumor recurrence or other
      illnesses. Multivariate analysis of OS revealed that MTV20%>40 ml was the only
      predictor of outcome with a lower 1-year OS [P=0.003, hazard ratio (HR)=2.29, 95%
      confidence interval (CI) 1.36-3.91]. Two independent predictors of DFS were
      MTV20%>40 ml (P=0.02, HR=1.78, 95% CI 1.09-2.91) and stage IV disease (P=0.01,
      HR=1.84, 95% CI 1.12-3.03). CONCLUSION: Pretreatment MTV20% is a novel marker for
      OS and DFS in patients with unresectable locally advanced esophageal cancer
      treated with definitive chemoradiotherapy. Treatment intensification must be
      considered for patients with higher MTVs.

PMID- 24276530
TI  - Hagen's gland morphology and chemical content analysis for three species of
      parasitic wasps (Hymenoptera: Braconidae).
AB  - The morphology and chemical content analysis of Hagen's glands of the braconid
      waspsBiosteres longicaudatus, B. tryoni, andB. arisanus were shown to be useful
      taxonomic markers.B. longicaudatus glands contain two components tentatively
      identified as (3aalpha,5beta,6aalpha)-5-butyltetrahydro-furo[3,2-b]furan-2(3H)
      one and a corresponding 5-hexyl derivative, whileB. tryoni glands contained
      dodecan-4-olide andB. arisanus glands contained ethyl octanoate, ethylZ-4
      octenoate, and octan-4-olide. 

PMID- 24276531
TI  - Individual variation in aggregation pheromone content of the bark beetle,Ips
      typographus.
AB  - The total amounts of, and proportions among, components of the aggregation
      pheromone produced byIps typographus were found to vary considerably among
      individuals excised from attacks on standing spruce trees. Chemical analyses of
      392 individual male beetles were made by GC-MS. Both unmated and mated males had
      log-normal frequency distributions in their content of the pheromone components 2
      methyl-3-buten-2-ol (MB) andcis-verbenol (cV), since a large fraction of males
      had a low content. The amount of MB in male hindguts varied independently of cV
      and the other oxygenated monoterpenes, while the amount of cV covaried with the
      other pinene alcohols and showed a variation between beetles from different
      spruce trees. Mated males had, on average, lower amounts of MB than unmated,
      while the average content of cV in mated males varied with the resin content of
      their host trees. Ipsdienol and ipsenol were only found in mated males, but in
      less than 40% and 10%, respectively, of these mated males. Even-aged males
      exposed to alpha-pinene in the laboratory showed slightly less variation in the
      amounts of verbenols, and the variations in ratio between cV and tV were similar
      to those among males attacking the same spruce tree. 

PMID- 24276532
TI  - Rumex obtusifolius L: Release of allelochemical agents and their influence on
      small-scale spatial distribution of meadow species.
AB  - DecomposingRumex obtusifolius L. leaves and their extracts were most toxic for
      germination and root growth of meadow speciesLolium perenne, Trifolium repens,
      Poa pratensis, andDactylis glomerata after seven days' decomposition, although
      the toxicity level was, in some cases, still high after 21 days. The hypothesis
      thatR. obtusifolius exerts allelopathic control over meadow species is supported
      by small-scale distribution of meadow species in the neighborhood ofR.
      obtusifolius plants. The area affected and the intensity of the effect both
      increase with the size of the individualR. obtusifolius plant. 

PMID- 24276533
TI  - Asymmetric small-scale distribution and allelopathy: Interaction betweenRumex
      obtusifolius L. and meadow species.
AB  - Analysis of small-scale distribution may allow allelopathic interaction among
      plant species to be distinguished from competitive interaction. If all
      environmental factors except slope are uniform, allelopathy produces spatial
      asymmetry in the association with a hypothetical receptor species and the
      corresponding hypothetical emitter species in the neighborhood of the latter. The
      interaction betweenRumex obtusifolius and the meadow speciesLolium perenne, Poa
      pratensis, Dactylis glomerata, andTrifolium repens is analyzed by way of example.

PMID- 24276534
TI  - The antidote for unprepared patients: a caring clinician.

PMID- 24276535
TI  - Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical
      strategy, and a review of the literature.
AB  - Mutations in the EFEMP2 (alias FBLN4) gene, which encodes the extracellular
      matrix protein fibulin-4, lead to severe aortopathy with aneurysm formation and
      vascular tortuosity. The disease phenotype, termed autosomal recessive cutis laxa
      type 1B (ARCL 1B), is rare among heritable connective tissue diseases but becomes
      more likely when noting family consanguinity and loose, inelastic skin in the
      patient. Our patient presented with an intercurrent illness exacerbating upper
      airway obstruction due to compression from a large aortic aneurysm. Genetic
      testing eventually revealed the causative mutation. She was initially treated
      with an angiotensin II receptor blocker and beta-blocker and eventually underwent
      total thoracic aortic replacement via a two-stage elephant trunk-type procedure.
      She recovered well and is currently asymptomatic but will require lifetime follow
      up due to residual vascular tortuosity and aneurysm risk. CONCLUSION: Better
      understanding of the importance of transforming growth factor beta signaling in
      the pathophysiology of aortopathies such as ARCL 1B has led to targeted medical
      therapies. Specific surgical techniques can lead to optimal outcomes in these
      patients.

PMID- 24276536
TI  - Disentangling the population structure and evolution of the clam pathogen Vibrio
      tapetis.
AB  - Vibrio tapetis is a fastidious slow-growing microorganism that causes the Brown
      Ring Disease in clams. Recently, two subspecies for this bacterial pathogen have
      been proposed. We have developed a multilocus sequence typing scheme and
      performed evolutionary studies of V. tapetis population using the great majority
      of isolates of V. tapetis obtained worldwide until now (30 isolates). V. tapetis
      constitutes a high polymorphic population, showing low diversity indexes and some
      genetic discontinuity among the isolates. Mutation events are more frequent than
      recombination, although both are approximately equally important for genetic
      diversification. In fact, the divergence between subspecies occurred exclusively
      by mutation but the diversity observed among isolates of the same subspecies
      appeared to be generated mostly by recombination. Between the subspecies, genetic
      distance is very high and almost no recurrent gene flow exists. This pathogen
      displays a non-clonal population structure with an ancient spatial segregation
      population and some degree of geographical isolation, followed by a population
      expansion, at least for V. tapetis subsp. tapetis. A database from this study was
      created and hosted on publmlst.org ( http://pubmlst.org/vtapetis/ ). 

PMID- 24276537
TI  - Geographical and temporal changes of foliar fungal endophytes associated with the
      invasive plant Ageratina adenophora.
AB  - Endophytes may gradually accumulate in the new geographic range of a non-native
      plant, just as pathogens do. To test this hypothesis, the dynamics of
      colonization and diversity of foliar fungal endophytes of non-native Ageratina
      adenophora were investigated. Previous reports showed that the time since the
      initial introduction (1930s) of A. adenophora into China varied among
      populations. Endophytes were sampled in three provinces of Southwest China in 21
      sites that varied from 20 to 70 years since the introduction of A. adenophora
      from its native Central America. Endophyte isolation frequencies varied from
      1.87% to 60.23% overall in a total of 4,032 leaf fragments. Based on ITS sequence
      variations, 463 fungal endophytes were distinguished as 112 operational taxonomic
      units (OTUs) belonging to the Sordariomycetes (77 OTUs, 373 isolates),
      Dothideomycetes (18 OTUs, 38 isolates), and Agaricomycetes (17 OTUs, 52 strains)
      classes. Colletotrichum (28.51%), Nemania (14.90%), Phomopsis (13.17%), and
      Xylaria (4.97%) were the most abundant genera. Both endophyte diversity and
      overall isolation frequency increased with time since introduction. The genetic
      differentiation of the fungus Colletotrichum gloeosporioides indicated that the
      dispersal of endophytes was likely affected by a combination of geographic
      factors and the invasion history of the host A. adenophora.

PMID- 24276539
TI  - Pyrosequencing reveals contrasting soil bacterial diversity and community
      structure of two main winter wheat cropping systems in China.
AB  - Microbes are key components of the soil environment, playing an important role in
      maintaining soil health, sustainability, and productivity. The composition and
      structure of soil bacterial communities were examined in winter wheat-rice (WR)
      and winter wheat-maize (WM) cropping systems derived from five locations in the
      Low-Middle Yangtze River plain and the Huang-Huai-Hai plain by pyrosequencing of
      the 16S ribosomal RNA gene amplicons. A total of 102,367 high quality sequences
      were used for multivariate statistical analysis and to test for correlation
      between community structure and environmental variables such as crop rotations,
      soil properties, and locations. The most abundant phyla across all soil samples
      were Proteobacteria, Acidobacteria, and Bacteroidetes. Similar patterns of
      bacterial diversity and community structure were observed within the same
      cropping systems, and a higher relative abundance of anaerobic bacteria was found
      in WR compared to WM cropping systems. Variance partitioning analysis revealed
      complex relationships between bacterial community and environmental variables.
      The effect of crop rotations was low but significant, and interactions among soil
      properties, locations, and crop rotations accounted for most of the explained
      variation in the structure of bacterial communities. Soil properties such as pH,
      available P, and available K showed higher correlations (positive or negative)
      with the majority of the abundant taxa. Bacterial diversity (the Shannon index)
      and richness (Chao1 and ACE) were higher under WR than WM cropping systems. 

PMID- 24276538
TI  - Bacterial signaling ecology and potential applications during aquatic biofilm
      construction.
AB  - In their natural environment, bacteria and other microorganisms typically grow as
      surface-adherent biofilm communities. Cell signal processes, including quorum
      signaling, are now recognized as being intimately involved in the development and
      function of biofilms. In contrast to their planktonic (unattached) counterparts,
      bacteria within biofilms are notoriously resistant to many traditional
      antimicrobial agents and so represent a major challenge in industry and medicine.
      Although biofilms impact many human activities, they actually represent an
      ancient mode of bacterial growth as shown in the fossil record. Consequently,
      many aquatic organisms have evolved strategies involving signal manipulation to
      control or co-exist with biofilms. Here, we review the chemical ecology of
      biofilms and propose mechanisms whereby signal manipulation can be used to
      promote or control biofilms. 

PMID- 24276540
TI  - Gold(III) reduction by the rhizobacterium Azospirillum brasilense with the
      formation of gold nanoparticles.
AB  - For the soil nitrogen-fixing bacterium Azospirillum brasilense, the ability to
      reduce [AuCl4](-) and to form gold nanoparticles (GNPs) has been demonstrated,
      with the appearance of a mauve tint of the culture. To validate the shapes and
      chemical nature of nanoparticles, transmission electron microscopy (TEM) and X
      ray fluorescence analysis were used. For the widely studied agriculturally
      important wild-type strains A. brasilense Sp7 and Sp245, GNPs formed after 10
      days of incubation of cell biomass with 0.25 mM [AuCl4](-) were shown (using TEM)
      to be mainly of spherical form (5 to 20 nm in diameter), with rare occasional
      triangles. In the course of cultivation with [AuCl4](-), after 5 days, a mauve
      tint was already visible for cells of strain Sp245.5, after 6 days for Sp245 and
      after 10 days for Sp7. Thus, for the mutant strain Sp245.5 (which has significant
      differences in the structure and composition of cell-surface polysaccharides as
      compared with Sp245), a more rapid formation of GNPs was observed. Moreover,
      their TEM images (also obtained after 10 days) showed different shapes: nano
      sized spheres, triangles, hexagons and rods, as well as larger round-shaped
      flower-like nanoparticles about 100 nm in size. Since by the time of GNP
      formation in our experiments the cells were found to be already not viable, this
      confirms the dominating role of cell surface structure and chemical composition
      in shaping the GNPs formed in the course of [AuCl4](-) reduction to Au(0). This
      finding may be useful for understanding the natural biogeochemical mechanisms of
      gold reduction and formation of GNPs involving microorganisms. The data obtained
      may also help in developing protocols for environmentally friendly synthesis of
      nanoparticles and possible use of bacterial cells with modified surface structure
      and composition for their fabrication. 

PMID- 24276541
TI  - Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to
      Sox9-regulated genes.
AB  - Histone modification, a critical step for epigenetic regulation, is an important
      modulator of biological events. Sox9 is a transcription factor critical for
      endochondral ossification; however, proof of its epigenetic regulation remains
      elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a
      transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and
      synergistically induces chondrogenesis. Growth of Arid5b(-/-) mice is retarded
      with delayed endochondral ossification. Sox9-dependent chondrogenesis is
      attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine
      demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2
      demethylation of these genes. In the promoters of chondrogenic marker genes,
      H3K9me2 levels are increased in Arid5b(-/-) chondrocytes. Finally, we show that
      Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings
      establish an epigenomic mechanism of skeletal development, whereby Arid5b
      promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of
      Sox9-regulated chondrogenic gene promoters. 

PMID- 24276542
TI  - Numerical and experimental evaluation of RF shimming in the human brain at 9.4 T
      using a dual-row transmit array.
AB  - OBJECTIVE: To provide a numerical and experimental investigation of the static RF
      shimming capabilities in the human brain at 9.4 T using a dual-row transmit
      array. MATERIALS AND METHODS: A detailed numerical model of an existing 16
      channel, inductively decoupled dual-row array was constructed using time-domain
      software together with circuit co-simulation. Experiments were conducted on a 9.4
      T scanner. Investigation of RF shimming focused on B1(+) homogeneity, efficiency
      and local specific absorption rate (SAR) when applied to large brain volumes and
      on a slice-by-slice basis. RESULTS: Numerical results were consistent with
      experiments regarding component values, S-parameters and B1(+) pattern, though
      the B1(+) field was about 25% weaker in measurements than simulations. Global
      shim settings were able to prevent B1(+) field voids across the entire brain but
      the capability to simultaneously reduce inhomogeneities was limited. On a slice
      by-slice basis, B1(+) standard deviations of below 10% without field dropouts
      could be achieved in axial, sagittal and coronal orientations across the brain,
      even with phase-only shimming, but decreased B1(+) efficiency and SAR limitations
      must be considered. CONCLUSION: Dual-row transmit arrays facilitate flexible 3D
      RF management across the entire brain at 9.4 T in order to trade off B1(+)
      homogeneity against power-efficiency and local SAR.

PMID- 24276543
TI  - Synthesis of substituted pyrenes by indirect methods.
AB  - The pyrene nucleus is a valuable component for materials, supramolecular and
      biological chemistry, due to its photophysical/electronic properties and extended
      rigid structure. However, its exploitation is hindered by the limited range of
      methods and outcomes for the direct substitution of pyrene itself. In response to
      this problem, a variety of indirect methods have been developed for preparing
      pyrenes with less usual substitution patterns. Herein we review these approaches,
      covering methods which involve reduced pyrenes, transannular ring closures and
      cyclisations of biphenyl intermediates. We also showcase the diverse range of
      substituted pyrenes which have been reported in the literature, and can serve as
      building blocks for new molecular architectures. 

PMID- 24276544
TI  - Nanochannel-based electrochemical sensor for the detection of pharmaceutical
      contaminants in water.
AB  - Effective real-time monitoring is the key to understanding and tackling the issue
      of pharmaceutical contamination of water. This research demonstrates the utility
      of an alumina nanochannel-based electrochemical sensor platform for the detection
      of ibuprofen in water derived from various sources. Our results indicate that the
      sensor is highly sensitive with a limit of detection at 0.25 pg mL(-1). The novel
      sensor described here has potential for application as a simple, rapid,
      inexpensive and highly reliable method for real-time environmental water quality
      assessment. 

PMID- 24276545
TI  - The MCART consortium animal models series: an evolving MCART.

PMID- 24276546
TI  - PEGylated G-CSF (BBT-015), GM-CSF (BBT-007), and IL-11 (BBT-059) analogs enhance
      survival and hematopoietic cell recovery in a mouse model of the hematopoietic
      syndrome of the acute radiation syndrome.
AB  - Hematopoietic growth factors (HGF) are recommended therapy for high dose
      radiation exposure, but unfavorable administration schedules requiring early and
      repeat dosing limit the logistical ease with which they can be used. In this
      report, using a previously described murine model of H-ARS, survival efficacy and
      effect on hematopoietic recovery of unique PEGylated HGF were investigated. The
      PEGylated-HGFs possess longer half-lives and more potent hematopoietic properties
      than corresponding non-PEGylated-HGFs. C57BL/6 mice underwent single dose lethal
      irradiation (7.76-8.72 Gy, Cs, 0.62-1.02 Gy min) and were treated with various
      dosing regimens of 0.1, 0.3, and 1.0 mg kg of analogs of human PEG-G-CSF, murine
      PEG-GM-CSF, or human PEG-IL-11. Mice were administered one of the HGF analogs at
      24-28 h post irradiation, and in some studies, additional doses given every other
      day (beginning with the 24-28 h dose) for a total of three or nine doses. Thirty
      day (30 d) survival was significantly increased with only one dose of 0.3 mg kg
      of PEG-G-CSF and PEG-IL-11 or three doses of 0.3 mg kg of PEG-GM-CSF (p <=
      0.006). Enhanced survival correlated with consistently and significantly enhanced
      WBC, NE, RBC, and PLT recovery for PEG-G- and PEG-GM-CSF, and enhanced RBC and
      PLT recovery for PEG-IL-11 (p <= 0.05). Longer administration schedules or higher
      doses did not provide a significant additional survival benefit over the shorter,
      lower dose, schedules. These data demonstrate the efficacy of BBT's PEG-HGF to
      provide significantly increased survival with fewer injections and lower drug
      doses, which may have significant economic and logistical value in the aftermath
      of a radiation event. 

PMID- 24276547
TI  - Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model
      of lethal H-ARS, and residual bone marrow damage in treated survivors.
AB  - In an effort to expand the worldwide pool of available medical countermeasures
      (MCM) against radiation, the PEGylated G-CSF (PEG-G-CSF) molecules Neulasta and
      Maxy-G34, a novel PEG-G-CSF designed for increased half-life and enhanced
      activity compared to Neulasta, were examined in a murine model of the
      Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS), along with the
      lead MCM for licensure and stockpiling, G-CSF. Both PEG-G-CSFs were shown to
      retain significant survival efficacy when administered as a single dose 24 h post
      exposure, compared to the 16 daily doses of G-CSF required for survival efficacy.
      Furthermore, 0.1 mg kg of either PEG-G-CSF affected survival of lethally
      irradiated mice that was similar to a 10-fold higher dose. The one dose/low dose
      administration schedules are attractive attributes of radiation MCM given the
      logistical challenges of medical care in a mass casualty event. Maxy-G34-treated
      mice that survived H-ARS were examined for residual bone marrow damage (RBMD) up
      to 9 mo post-exposure. Despite differences in Sca-1 expression and cell cycle
      position in some hematopoietic progenitor phenotypes, Maxy-G34-treated mice
      exhibited the same degree of hematopoietic stem cell (HSC) insufficiency as
      vehicle-treated H-ARS survivors in competitive transplantation assays of 150
      purified Sca-1+cKit+lin-CD150+cells. These data suggest that Maxy-G34, at the
      dose, schedule, and time frame examined, did not mitigate RBMD but significantly
      increased survival from H-ARS at one-tenth the dose previously tested, providing
      strong support for advanced development of Maxy-G34, as well as Neulasta, as MCM
      against radiation. 

PMID- 24276548
TI  - The ability of filgrastim to mitigate mortality following LD50/60 total-body
      irradiation is administration time-dependent.
AB  - The identification of the optimal administration schedule for an effective
      medical countermeasure is critical for the effective treatment of individuals
      exposed to potentially lethal doses of radiation. The efficacy of filgrastim
      (Neupogen(r)), a potential medical countermeasure, to improve survival when
      initiated at 48 h following total body irradiation in a non-human primate model
      of the hematopoietic syndrome of the acute radiation syndrome was investigated.
      Animals were exposed to total body irradiation, antero-posterior exposure, total
      midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy
      min, using linear accelerator-derived 6 MV photons. All animals were administered
      medical management. Following irradiation on day 0, filgrastim (10 MUg kg d) or
      the control (5% dextrose in water) was administered subcutaneously daily through
      effect (absolute neutrophil count >= 1,000 cells MUL for three consecutive days).
      The study (n = 80) was powered to demonstrate a 25% improvement in survival
      following the administration of filgrastim or control beginning at 48 +/- 4 h
      post-irradiation. Survival analysis was conducted on the intention-to-treat
      population using a two-tailed null hypothesis at a 5% significance level.
      Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5%
      increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure
      to mitigate lethality in the hematopoietic syndrome of the acute radiation
      syndrome can be dependent on the interval between irradiation and administration
      of the medical countermeasure. 

PMID- 24276549
TI  - Characterization of the dose response relationship for lung injury following
      acute radiation exposure in three well-established murine strains: developing an
      interspecies bridge to link animal models with human lung.
AB  - Approval of radiation countermeasures through the FDA Animal Rule requires
      pivotal efficacy screening in one or more species that are expected to react with
      a response similar to humans (21 C.F.R. S 314.610, drugs; S 601.91, biologics).
      Animal models used in screening studies should reflect the dose response
      relationship (DRR), clinical presentation, and pathogenesis of lung injury in
      humans. Over the past 5 y, the authors have characterized systematically the
      temporal onset, dose-response relationship (DRR), and pathologic outcomes
      associated with acute, high dose radiation exposure in three diverse mouse
      strains. In these studies, C57L/J, CBA/J, and C57BL/6J mice received wide field
      irradiation to the whole thorax with shielding of the head, abdomen, and
      forelimbs. Doses were delivered at a rate of 69 cGy min using an x-ray source
      operated at 320 kVp with half-value layer (HVL) of 1 mm Cu. For all strains,
      radiation dose was associated significantly with 180 d mortality (p < 0.0001).
      The lethal dose for 50% of animals within the first 180 d (LD50/180) was 11.35 Gy
      (95% CI 11.1-11.6 Gy) for C57L/J mice, 14.17 Gy (95% CI 13.9-14.5 Gy) for CBA/J
      mice, and 14.10 Gy (95% CI 12.2-16.4 Gy) for C57BL/6J mice. The LD50/180 in the
      C57L/J strain was most closely analogous to the DRR for clinical incidence of
      pneumonitis in non-human primates (10.28 Gy; 95% CI 9.9-10.7 Gy) and humans
      (10.60 Gy; 95% CI 9.9-12.1 Gy). Furthermore, in the C57L/J strain, there was no
      gender-specific difference in DRR (p = 0.5578). The reliability of the murine
      models is demonstrated by the reproducibility of the dose-response and
      consistency of disease presentation across studies.Health Phys. 106(1):000-000;
      2014. 

PMID- 24276550
TI  - The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus
      macaque model.
AB  - Several radiation dose- and time-dependent tissue sequelae develop following
      acute high-dose radiation exposure. One of the recognized delayed effects of such
      exposures is lung injury, characterized by respiratory failure as a result of
      pneumonitis that may subsequently develop into lung fibrosis. Since this
      pulmonary subsyndrome may be associated with high morbidity and mortality,
      comprehensive treatment following high-dose irradiation will ideally include
      treatments that mitigate both the acute hematologic and gastrointestinal
      subsyndromes as well as the delayed pulmonary syndrome. Currently, there are no
      drugs approved by the Food and Drug Administration to counteract the effects of
      acute radiation exposure. Moreover, there are no relevant large animal models of
      radiation-induced lung injury that permit efficacy testing of new generation
      medical countermeasures in combination with medical management protocols under
      the FDA animal rule criteria. Herein is described a nonhuman primate model of
      delayed lung injury resulting from whole thorax lung irradiation. Rhesus macaques
      were exposed to 6 MV photon radiation over a dose range of 9.0-12.0 Gy and
      medical management administered according to a standardized treatment protocol.
      The primary endpoint was all-cause mortality at 180 d. A comparative
      multiparameter analysis is provided, focusing on the lethal dose response
      relationship characterized by a lethal dose50/180 of 10.27 Gy [9.88, 10.66] and
      slope of 1.112 probits per linear dose. Latency, incidence, and severity of lung
      injury were evaluated through clinical and radiographic parameters including
      respiratory rate, saturation of peripheral oxygen, corticosteroid requirements,
      and serial computed tomography. Gross anatomical and histological analyses were
      performed to assess radiation-induced injury. The model defines the dose response
      relationship and time course of the delayed pulmonary sequelae and consequent
      morbidity and mortality. Therefore, it may provide an effective platform for the
      efficacy testing of candidate medical countermeasures against the delayed
      pulmonary syndrome. 

PMID- 24276551
TI  - A pilot study in rhesus macaques to assess the treatment efficacy of a small
      molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in
      mitigating radiation-induced lung damage.
AB  - The objective of this pilot study was to explore whether administration of a
      catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation
      induced lung injury and improve overall survival when administered after 11.5 Gy
      of whole thorax lung irradiation in a non-human primate model. Thirteen animals
      were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and
      delivered with 6 MV photons at a dose rate of 0.8 Gy min. Beginning at 24 h post
      irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections
      of the catalytic antioxidant at a concentration of 5 mg kg for a total of 4 wk.
      All animals received medical management, including dexamethasone, based on
      clinical signs during the planned 180-d in-life phase of the study. All decedent
      study animals were euthanized for failure to maintain saturation of peripheral
      oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in
      radiation-induced lung injury in all animals. AEOL 10150, as administered in this
      pilot study, demonstrated potential efficacy as a mitigator against fatal
      radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival
      following exposure to a radiation dose that proved to be 100% fatal in the
      control cohort (n = 6). Computed tomography scans demonstrated less quantitative
      radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated
      cohort at day 60 post-exposure, and AEOL 10150-treated animals required less
      dexamethasone support during the in-life phase of the study. Analysis of serial
      plasma samples suggested that AEOL 10150 treatment led to lower relative
      transforming growth factor-Beta-1 levels when compared with the control animals.
      The results of this pilot study demonstrate that treatment with AEOL 10150
      results in reduced clinical, radiographic, anatomic, and molecular evidence of
      radiation-induced lung injury and merits further study as a medical
      countermeasure against radiation-induced pulmonary injury. 

PMID- 24276552
TI  - Immune cell reconstitution after exposure to potentially lethal doses of
      radiation in the nonhuman primate.
AB  - Delayed immune reconstitution remains a major cause of morbidity associated with
      myelosuppression induced by cytotoxic therapy or myeloablative conditioning for
      stem cell transplant, as well as potentially lethal doses of total- or partial
      body irradiation. Restoration of a functional immune cell repertoire requires
      hematopoietic stem cell reconstitution for all immune cells and effective
      thymopoiesis for T cell recovery. There are no medical countermeasures available
      to mitigate damage consequent to high-dose, potentially lethal irradiation, and
      there are no well characterized large animal models of prolonged
      immunosuppression to assess efficacy of potential countermeasures. Herein, the
      authors describe a model of T and B cell reconstitution following lethal doses of
      partial-body irradiation with 5% bone marrow sparing that includes full exposure
      of the thymus. Rhesus macaques (n = 31 male, 5.5-11.3 kg body weight) were
      exposed to midline tissue doses of 9.0-12.0 Gy using 6 MV LINAC-derived photons
      at a dose rate of 0.80 Gy min, sparing approximately 5% of bone marrow (tibiae,
      ankles, and feet). All animals received medical management and were monitored for
      myeloid and lymphoid suppression and recovery through 180 d post-exposure.
      Myeloid recovery was assessed by neutrophil and platelet-related hematological
      parameters. Reconstitution of B and T cell subsets was assessed by flow
      cytometric immunophenotyping, and recent thymic emigrants were identified by RT
      PCR of T cell receptor excision circles. Mortality was recorded through 180 d
      post-exposure. Acute myelo-suppression was characterized by severe neutropenia
      and thrombocytopenia, followed by recovery 30-60 d post-exposure. Total T (CD3+)
      and B (CD20+) cells were reduced significantly following exposure and exhibited
      differential recovery patterns post-exposure. Both CD4+ and CD8+ subsets of naive
      T cells and total CD4+ T cell counts remained significantly lower than baseline
      through 180 d post-exposure. The failure of recent thymic emigrants and naive T
      cell subsets to recover to normal baseline values reflects the severe radiation
      effects on the recovery of marrow-derived stem and early thymic progenitor cells,
      their mobilization and seeding of receptive thymic niches, and slow endogenous
      thymic regeneration. 

PMID- 24276553
TI  - The MCART radiation physics core: the quest for radiation dosimetry
      standardization.
AB  - Dose-related radiobiological research results can only be compared meaningfully
      when radiation dosimetry is standardized. To this purpose, the National Institute
      of Allergy and Infectious Diseases (NIAID)-sponsored Medical Countermeasures
      Against Radiological Threats (MCART) consortium recently created a Radiation
      Physics Core (RPC) as an entity to assume responsibility of standardizing
      radiation dosimetry practices among its member laboratories. The animal research
      activities in these laboratories use a variety of ionizing photon beams from
      several irradiators such as 250-320 kVp x-ray generators, Cs irradiators, Co
      teletherapy machines, and medical linear accelerators (LINACs). In addition to
      this variety of sources, these centers use a range of irradiation techniques and
      make use of different dose calculation schemes to conduct their experiments. An
      extremely important objective in these research activities is to obtain a Dose
      Response Relationship (DRR) appropriate to their respective organ-specific models
      of acute and delayed radiation effects. A clear and unambiguous definition of the
      DRR is essential for the development of medical countermeasures. It is imperative
      that these DRRs are transparent between centers. The MCART RPC has initiated the
      establishment of standard dosimetry practices among member centers and is
      introducing a Remote Dosimetry Monitoring Service (RDMS) to ascertain ongoing
      quality assurance. This paper will describe the initial activities of the MCART
      RPC toward implementing these standardization goals. It is appropriate to report
      a summary of initial activities with the intent of reporting the full
      implementation at a later date. 

PMID- 24276554
TI  - Identification and quantitation of biomarkers for radiation-induced injury via
      mass spectrometry.
AB  - Biomarker identification and validation for radiation exposure is a rapidly
      expanding field encompassing the need for well defined animal models and advanced
      analytical techniques. The resources within the consortium, Medical
      Countermeasures Against Radiological Threats (MCART), provide a unique
      opportunity for accessing well defined animal models that simulate the key
      sequelae of the acute radiation syndrome and the delayed effects of acute
      radiation exposure. Likewise, the use of mass spectrometry-based analytical
      techniques for biomarker discovery and validation enables a robust analytical
      platform that is amenable to a variety of sample matrices and considered the
      benchmark for biomolecular identification and quantitation. Herein, the authors
      demonstrate the use of two targeted mass spectrometry approaches to link
      established MCART animal models to identified metabolite biomarkers. Circulating
      citrulline concentration was correlated to gross histological gastrointestinal
      tissue damage, and retinoic acid production in lung tissue was established to be
      reduced at early and late time points post high dose irradiation. Going forward,
      the use of mass spectrometry-based metabolomics coupled to well defined animal
      models provides the unique opportunity for comprehensive biomarker discovery. 

PMID- 24276555
TI  - Mass spectrometry imaging enriches biomarker discovery approaches with candidate
      mapping.
AB  - Integral to the characterization of radiation-induced tissue damage is the
      identification of unique biomarkers. Biomarker discovery is a challenging and
      complex endeavor requiring both sophisticated experimental design and accessible
      technology. The resources within the National Institute of Allergy and Infectious
      Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against
      Radiological Threats (MCART), allow for leveraging robust animal models with
      novel molecular imaging techniques. One such imaging technique, MALDI (matrix
      assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for
      the direct spatial visualization of lipids, proteins, small molecules, and
      drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires
      mass spectra directly from an intact tissue slice in discrete locations across an
      x, y grid that are then rendered into a spatial distribution map composed of ion
      mass and intensity. The unique mass signals can be plotted to generate a spatial
      map of biomarkers that reflects pathology and molecular events. The crucial
      unanswered questions that can be addressed with MALDI-MSI include identification
      of biomarkers for radiation damage that reflect the response to radiation dose
      over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI
      also enable integration of biomarker identification among diverse animal models.
      Analysis of early, sublethally irradiated tissue injury samples from diverse
      mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated
      with histological features of these unique tissues. This paper will discuss the
      application of MALDI-MSI for use in a larger biomarker discovery pipeline. 

PMID- 24276556
TI  - Linking the human response to unplanned radiation and treatment to the nonhuman
      primate response to controlled radiation and treatment.
AB  - A key difficulty in developing countermeasures against radiation-induced health
      impairments is the clear lack of controlled clinical studies, due to the
      relatively low number of radiation victims worldwide. Instead, established and
      accepted animal models, as well as the recommendations of national and
      international expert panels and committees, are the main sources of information.
      Therefore, the development of countermeasures requires comparison of data from
      many sources and accumulation of information consistent with the U. S. Food and
      Drug Administration's "Animal Rule." A new approach is the comparative analysis
      of human data from the SEARCH (System for Evaluation and Archiving of Radiation
      Accidents based on Case Histories) database and data from nonhuman primate (NHP)
      animal model studies. The SEARCH database contains 824 clinical cases from 81
      radiation accidents in 19 countries. This exceptional collection of clinical data
      from accidentally radiation-exposed persons is analyzed regarding clinical signs
      and symptoms of radiation-induced health impairments. To analyze the time course
      of radiation syndromes, clinical parameters common to the SEARCH and NHP
      databases have to be assigned into comparable categories of clinical severity for
      each species. The goal is to establish a method for comparison of human and NHP
      data, validate the NHP data as a surrogate for human efficacy/clinical studies,
      and open a way for the extraction of diagnostic and treatment methods for humans
      after radiation exposure according to relevant regulations. 

PMID- 24276560
TI  - Progesterone and estrogen receptors in conjunctival melanoma and nevi.
AB  - BACKGROUND: Since it has been observed that melanocytic lesions can alter their
      appearance during pregnancy, we analyzed whether hormone receptors are expressed
      in conjunctival nevi as well as conjunctival melanoma. We further analyzed
      whether the number of estrogen (ER) or progesterone receptors (PR) might be
      associated with the disease course in conjunctival melanoma. METHODS: Twenty
      seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma
      specimens were examined using immunohistological analysis with antibodies against
      PR and ER. The percentage of stained cells were analyzed, taking into account
      patient gender and age. Out of the melanoma group, all patients with complete
      data for tumor thickness, tumor localization, age at diagnosis, gender, and
      follow-up including recurrence, metastasis and tumor-related death were included
      in the second part of the study (n = 15), where hormone receptor rates were
      associated with tumor outcome, regarding recurrences, metastasis or death.
      Written consent was received from all included patients. RESULTS: Both nevi and
      melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 +/- 25 % of
      cells stained positive for PR and 35 +/- 34 % for ER. In melanoma specimens, 68
      +/- 30 % showed PR and 44 +/- 34 % ER expression. Differences between men and
      women in expression rates were not statistically significant. Out of 15 melanoma
      patients (nine female, six male), 53 % (five women and three men) experienced 1-4
      recurrences, and four patients developed metastases. The median estimated
      survival time was 12.2 years. A multivariate survival model taking into account
      known risk factors for prognosis in conjunctival melanoma confirmed tumor
      location to be an important predictive factor for outcome (p = 0.05). The rate of
      PR or ER did not show a statistically significant correlation with the disease
      course in our cohort. CONCLUSIONS: We observed that conjunctival melanocytic
      lesions express hormone receptors, which could explain why these tumors can alter
      their appearance under hormonal changes. Regarding the prognosis of conjunctival
      melanoma, no statistically significant correlation between hormone receptor
      expression and event-free survival was found in this analysis.

PMID- 24276561
TI  - Characterisation of reticular pseudodrusen and their central target aspect in
      multi-spectral, confocal scanning laser ophthalmoscopy.
AB  - BACKGROUND: To analyse reticular pseudodrusen (RPD) in patients with age-related
      macular degeneration (AMD) using multi-spectral (MS), confocal scanning laser
      ophthalmoscopy (cSLO). METHODS: cSLO images (blue fundus autofluorescence [FAF;
      exc., lambda = 488; em., lambda = 500-700 nm], near-infrared reflectance [IR;
      lambda = 820 nm], MS [blue reflectance (BR) lambda = 488 nm, green reflectance
      (GR) lambda = 515 nm, IR lambda = 820 nm], as well as colour fundus photographs
      (CFP) were taken of 200 eyes from 100 AMD patients suspected to show RPD on the
      basis of funduscopy or previous fundus imaging. FAF and IR images were graded by
      two independent readers. If both readers concordantly confirmed the presence of
      RPD in both modalities, eyes were subsequently also graded for RPD in MS, BR, GR,
      green-blue enhanced mode (GBE), and CFP. Besides, FAF, IR, and MS images were
      evaluated for the presence of a target aspect, which represents a common feature
      of RPD lesions. RESULTS: The presence of RPD was confirmed using FAF and IR
      images by both readers in 130 eyes of 76 patients. In those eyes, both readers
      concordantly diagnosed RPD in MS images in 124 (95.4%) eyes (BR: 52 [40.0%], GR:
      63 [48.5%], GBE: 101 [77.7%], CF: 27 [20.8%]). Cohen kappa statistics revealed
      excellent inter-observer agreement for MS (0.95) and GBE (0.85), substantial
      agreement for BR (0.75), GR (0.78), and moderate agreement for CFP (0.59). A
      target aspect within RPD lesions was detected in 45 of 130 (35.0%) included eyes
      using FAF and IR. The presence of a target aspect improved the recognition of RPD
      lesions in all modalities. If a target aspect was present, RPD were diagnosed in
      45 eyes (100%) using MS (GBE: 42 eyes [93.3%], BR: 30 eyes [66.7%], GR: 37 eyes
      [82.2%], CFP: 17 eyes [37.8%]). Using MS cSLO, a target aspect could be
      identified in 75 of 130 (57.7%) included eyes. CONCLUSIONS: MS cSLO imaging is
      equivalent to FAF and IR in identifying RPD in AMD patients. Higher
      identification rates in BR and GR of those RPD lesions featuring a target aspect
      confirm the current hypothesis of RPD localisation and its progression further
      into the photoreceptor layers. MS seems to be more sensitive in identifying a
      central target aspect in RPD lesions compared to blue FAF and IR.

PMID- 24276563
TI  - Intraoperative floppy iris syndrome (IFIS): what complication rates can we
      expect?

PMID- 24276562
TI  - Myofibroblast and extracellular matrix origins in proliferative
      vitreoretinopathy.
AB  - BACKGROUND: To evaluate origins of the fibrocontractive cell populations and
      their relation to collagens I and II in proliferative vitreoretinopathy (PVR).
      METHODS: Human PVR membranes were evaluated by indirect immunofluorescence for
      GFAP, cytokeratin-18 (CK-18), alpha-smooth muscle actin (alphaSMA), collagens I
      and II. Collagen expression by porcine Muller and retinal pigment epithelial
      cells (RPE) was evaluated using RT-PCR of RNA harvested from freshly isolated
      primary and proliferating cultures. RESULTS: Collagen I was detected in all PVR
      samples and was widely distributed in the extracellular matrix. In contrast,
      collagen II was present in only two of the ten samples and was localized to thin,
      acellular bands near the border of the tissues. Using cell type-specific markers
      CK-18 and GFAP, RPE and glia were localized to the collagen I-rich matrices.
      Cells positive for GFAP and CK-18 can also co-express alphaSMA. Normal and
      proliferating RPE express collagen I, but Muller cells show no evidence of
      collagen I expression until they proliferate in culture. In contrast, normal RPE
      and Muller cells contain message for collagen II which is lost shortly after
      introduction into culture. CONCLUSIONS: Collagen I appears to be the predominate
      fibrillar collagen in human PVR membranes and collagen II a comparatively minor
      component. Muller cells and RPE are physically associated with the collagen I
      matrix and are capable of expressing this protein suggesting that they are the
      origin. It also appears that the majority of myofibroblasts in PVR membranes are
      derived from either RPE or Muller cells suggesting that they play a major role in
      membrane development.

PMID- 24276565
TI  - Breeding for nematode and virus resistance in potato via anther culture.
AB  - In Solanum tuberosum the production by parthenogenesis of 2x plants with 24
      chromosomes, and the regeneration of microspores of such dihaploids to yield
      monohaploid (1x) plants is reproducibly possible, at least for some specific
      genotypes. Experiments are described using tissue culture techniques in an
      applied breeding program with the main aim of increasing the level of resistance
      to the potato cyst nematode Globodera pallida (Stone) and to the potato viruses
      X, Y and leaf roll. These resistances follow quantitative as well as qualitative
      modes of inheritance. Using anther culture it is demonstrated that doubled
      monohaploid clones can be produced which possess the resistance in the homozygous
      condition. In both ways of inheritance the ratio of resistant clones is rather
      high. The genotype of the anther donor plant has, however, a strong influence on
      the total number of androgenetic plants which can be regenerated. Therefore,
      experiments were initiated with the aim of integrating this capacity for
      regeneration (tissue culture ability) into valuable genotypes. The results show
      that the potentiality for regeneration is under genetic control and can be
      utilized by combination breeding. Its inheritance and physiological basis, as
      well as the behaviour of complete homozygous clones, is discussed. 

PMID- 24276564
TI  - L-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in plasma
      and synovial fluid of patients with knee osteoarthritis.
AB  - BACKGROUND: The aim of this study was to investigate the involvement of the
      nitric oxide (NO) pathway in osteoarthritis (OA). MATERIAL AND METHODS: The study
      groups consisted of 32 patients with knee OA and 31 healthy controls. In
      peripheral venous blood samples (from the OA patients and the controls) and in
      synovial fluid samples (from the OA patients), the concentrations of L-arginine
      (ARN), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)
      were evaluated. In plasma samples, thiobarbituric acid reactive substances
      (TBARS) were also measured. RESULTS: Plasma ARN concentrations were lower in the
      OA patients than in controls (53.55 +/- 16.37 vs. 70.20 +/- 25.68 umol/l)
      (P<0.05), while plasma ADMA concentrations were similar. Accordingly, the
      ARN/ADMA ratio was lower in the OA patients than in the control group (80.85 +/-
      29.58 vs. 110.51 +/- 30.48, P<0.05). Plasma SDMA and TBARS concentrations were
      higher in the OA patients than in controls (0.69 +/- 0.15 vs. 0.60 +/- 0.10
      umol/l, P<0.05 and 1.21 +/- 0.29 vs. 0.55 +/- 0.12, respectively) (P<0.001). In
      the OA patients, ADMA concentrations were significantly higher in the synovial
      fluid than in plasma (0.75 +/- 0.09 vs. 0.69 +/- 0.14 umol/l, P<0.05), as were
      ARN concentrations (76.96 +/- 16.73 vs. 53.55 +/- 16.73 umol/l) (P<0.00001).
      Conclusions These results indicate a poor availability of NO in the synovial
      fluid of the OA patients, which may contribute to the progression of OA. The
      decreased ARN/ADMA ratio and the increased SDMA and TBARS in the plasma of the OA
      patients suggest an impairment of endothelial function in these subjects.

PMID- 24276566
TI  - Callus formation from protoplasts of a maize cell culture.
AB  - A finely dispersed cell suspension culture from the friable callus of the 'Black
      Mexican Sweet' line of maize was obtained. Protoplasts from this cell culture,
      when grown in a simplified medium described here, showed sustained cell divisions
      and gave rise to callus. 

PMID- 24276567
TI  - Genetics of glucose phosphate isomerase and phosphoglucomutase in Aedes
      albopictus (diptera: culicidae).
AB  - Glucose phosphate isomerase (E.C. 5.3.1.9) and phosphoglucomutase (E.C. 2.7.5.1)
      were found to be polymorphic in a laboratory colony of Aedes albopictus. The
      glucose phosphate isomerase locus is represented by two alleles resulting in
      three genotypes, while the phosphoglucomutase locus is represented by at least
      five alleles giving rise to a total of 15 genotypes. The inheritance of these two
      enzymes is of the Mendelian type with codominant alleles. Present data indicate
      that these genes are not linked.Of 105 mosquitoes analysed for these two gene
      enzyme systems, the frequencies for glucose phosphate isomerase alleles are Gpi
      (S)=0.68 and Gpi (F)=0.32, while the frequencies for phosphoglucomutase alleles
      are Pgm (A)=0.16, Pgm (B)=0.11, Pgm (C)=0.19, Pgm (D)=0.30 and Pgm (F)= 0.24. The
      frequencies of the three glucose phosphate isomerase genotypes are in accord with
      Hardy-Weinberg expectations (X 1 (2) =2.74). Similarly, the frequencies of the 15
      phosphoglucomutase genotypes probably do not differ significantly from Hardy
      Weinberg expectations (X 10 (2) = 18.45). 

PMID- 24276568
TI  - Fractionation of wheat gliadin and glutenin subunits by two-dimensional
      electrophoresis and the role of group 6 and group 2 chromosomes in gliadin
      synthesis.
AB  - Subunits of wheat endosperm proteins have been fractionated by two-dimensional
      electrophoresis. To determine which subunits in the two-dimensional
      electrophoretic pattern belong to gliadin or glutenin the endosperm proteins have
      also been fractionated by a modified Osborne procedure and by gel filtration on
      Sephadex G-100 and Sepharose CL-4B prior to separation by two-dimensional
      electrophoresis.The control of production of five major grain protein subunits is
      shown to be determined by chromosomes 6A, 6B and 6D by comparing two-dimensional
      electrophoretic protein subunit patterns of aneuploid lines of the variety
      'Chinese Spring'. From these and previous studies it is concluded that some
      alpha, beta and gamma gliadins (molecular weights by SDS-PAGE 30,000 to 40,000)
      are specified by genes on the short arms of homoeologous Group 6 chromosomes, the
      omega gliadins (molecular weights by SDS-PAGE 50,000 to 70,000) are specified by
      genes on the short arms of homoeologous Group 1 chromosomes and the glutenin
      subunits (molecular weights by SDS-PAGE > 85,000) are specified by genes on the
      long arms of homoeologous Group 1 chromosomes.No major gliadins or glutenin
      subunits were absent when any of the chromosomes in homoeologous Groups 2, 3, 4,
      5 or 7 were deleted. However two gliadins whose presumed structural genes are on
      chromosome 6D were absent in aneuploid stocks of 'Chinese Spring' carrying two
      additional doses of chromosome 2A. Two out of thirty-three intervarietal or
      interspecific chromosome substitution lines examined, involving homoeologous
      Group 2 chromosomes, lacked the same two gliadins. All the subunits in the other
      thirty-one chromosome substitution lines were indistinguishable from those in
      'Chinese Spring'. It is therefore concluded that the major variation affecting
      gliadin and glutenins in wheat is concentrated on the chromosomes of homoeologous
      Groups 1 and 6 but Group 2 chromosomes are candidates for further study.An
      endosperm protein controlled by chromosome 4D in 'Chinese Spring' is shown to be
      a high molecular weight globulin. 

PMID- 24276569
TI  - Genetic variation in wheat endosperm proteins: an analysis by two-dimensional
      electrophoresis using intervarietal chromosomal substitution lines.
AB  - The major endosperm proteins in a range of genotypes of hexaploid wheat have been
      fractionated by two-dimensional electrophoresis. The genotypes included nine
      varieties and forty four intervarietal substitution lines in which chromosomes
      1A, 1B, 1D, 6A, 6B or 6D from eight of the varieties have been introduced one at
      a time into a common genetic background. The appearance of different protein
      subunits was often correlated with a chromosome substitution. This showed that
      many of the genes for the high molecular weight protein subunits (molecular
      weight range 55,000 to 140,000 determined by SDS polyacrylamide gel
      electrophoresis) are specified by chromosomes 1A, 1B and 1D while many of the
      lower molecular weight subunits (molecular weight range 30,000 to 45,000) are
      specified by chromosomes 6A, 6B and 6D. The different protein subunits correlated
      with chromosome substitution could not always be recognised in the varietal
      source of the substituted chromosome. The different subunits specified by
      homologous chromosomes in different wheat varieties may differ in isoelectric
      point and/or molecular weight. 

PMID- 24276570
TI  - Gene number estimation when multiplicative genetic effects are assumed - growth
      in flour beetles and mice.
AB  - Estimation of the number of segregating genes affecting a quantitative trait in
      populations initiated from a cross of two homozygous lines is considered.
      Experimental data, for the trait in question, is assumed available on total
      response to recurrent selection initiated in the F2 or F3 generation, the initial
      additive genetic variance and the heterosis exhibited in the F1 generation.
      Appropriate procedures when multiplicative genetic effects are assumed are
      developed and reasons for assuming multiplicative rather than additive effects
      are indicated. These procedures were employed to estimate the number of genes
      affecting pupa weight in a population of flour beetles and growth in a population
      of mice. Estimates were 50-60 percent smaller than those obtained using familiar
      estimation procedures appropriate when no epistasis is assumed. However, the
      estimated numbers (about 200 and 100 for pupa weight and mouse growth,
      respectively) were still rather large. 

PMID- 24276571
TI  - Alternative strategies in fungal race-specific parasitism.
AB  - Based on the gene-for-gene relation in race-specific resistance versus virulence,
      racial complexity of a pathogen population can be revealed by using host lines
      each with a single gene for resistance as detector. Such inventories of cereal
      rusts have shown: i. Genes for virulence may have pleiotropic effects acting on
      general fitness and their relative prevalence. ii. Genes for virulence are, as
      most other genes, dependent on genetic background for their general fitness. iii.
      Specific and general gene erosion in a pathogen population submitted to the
      assortative function of a race-specific host selection pressure is proportional
      to the degree of existing recombination and thus ultimately upon mode of
      reproduction (sexual or asexual). iv. Genetic storage capacity is dependent on
      ploidy constitution. v. Host alternation for safe annual survival favours a
      genetic system able to store temporarily unnecessary genes for virulence. - Due
      to shifting circumstances, pathogens like rusts will even inside the same forma
      specialis show different strategies. The trend may lead to a process of
      stabilizing selection and dependence on immediate and provisional flexibility
      just as typical of true haploids. It may lead to a pattern of preparedness: i.e.
      accumulation of 'unnecessary' genes for virulence. In the latter case, the modern
      concept of gene diversification in breeding for disease resistance is less
      effective. In the former case, gene accumulation can also work. 

PMID- 24276572
TI  - Radiation stimulated increase of plating efficiency of free plant cells.
AB  - Radiation induced stimulation of plating efficiency of free plant cells was
      observed following irradiation with X-rays (1.25 Gy, dose rate 3.1 Gy.nin(-1))
      and fission neutrons (1.5 Gy, dose rate 0.05 Gy.nin(-1)). The dose range where
      the radiation stimulation effect is manifest is inversely correlated with the
      applied dose rate.The results are discussed in view of the radiation induced
      stimulation as it is applied in agricultural practice. 

PMID- 24276574
TI  - Effects of dietary beta-1,3/1,6-glucan on the antioxidant and digestive enzyme
      activities of Pacific red snapper (Lutjanus peru) after exposure to
      lipopolysaccharides.
AB  - The effect of beta-1,3/1,6-glucan, derived from yeast, on growth, antioxidant,
      and digestive enzyme performance of Pacific red snapper Lutjanus peru before and
      after exposure to lipopolysaccharides (LPS) was investigated. The beta-1,3/1,6
      glucan was added to the basal diet at two concentrations (0.1 and 0.2 %). The
      treatment lasted 6 weeks, with sampling at regular intervals (0, 2, 4, and 6
      weeks). At the end of this period, the remaining fish from either control or beta
      glucan-fed fish were injected intraperitoneally with LPS (3 mg kg(-1)) or with
      sterile physiological saline solution (SS) and then sampled at 0, 24, and 72 h.
      The results showed a significant increase (P < 0.05) in growth performance after
      6 weeks of feeding with beta-glucan. Superoxide dismutase (SOD) activity in liver
      was significantly higher in diets containing 0.1 % beta-glucan in weeks 4 and 6,
      compared to the control group. beta-Glucan supplementation at 0.1 and 0.2 %
      significantly increased aminopeptidase, trypsin, and chymotrypsin activity. At 72
      h after injection of LPS, we observed a significant increase in catalase activity
      in liver from fish fed diets supplemented with 0.1 and 0.2 % beta-glucan; SOD
      activity increased in fish fed with 0.1 % beta-glucan in relation to those
      injected with SS. Feed supplemented with beta-1,3/1,6-glucan increased growth,
      antioxidant activity, and digestive enzyme activity in Pacific red snapper. 

PMID- 24276575
TI  - A descriptive analysis of demographic and behavioral data from Internet gamblers
      and those who self-exclude from online gambling platforms.
AB  - As the popularity of internet gambling increases, the increased opportunities to
      participate serve to heighten concerns about the potential for gambling related
      harm. This paper focuses on self-exclusion as one of the main responsible gaming
      interventions, and is split into three sections. Firstly, we set out a three-tier
      model for assessing at-risk gambling behaviors which examines player exhibited,
      declared and inferred behavior. Secondly, we present a literature review relating
      to who self-excludes and whether self-exclusion is effective. Finally, we report
      the results of an analysis of the exhibited behavior of internet self-excluders
      as sampled from a research cohort of over 240,000 internet gaming accounts. Our
      analysis of self-excluders (N = 347) versus a control group (N = 871) of gamblers
      indicates self-excluders are younger than the control group, more likely to
      suffer losses and more likely to adopt riskier gambling positions. Unlike some
      previous studies, there was little difference in terms of mean gambling hours per
      month or minutes per session. Some self-excluders (N = 306) can be tracked from
      the date their account was created through their self-exclusion history,
      indicating a large number of very quick self-exclusions (e.g., 25 % within a day)
      and a small set of serial self-excluders. Younger and older males are likely to
      self-exclude faster than middle-aged males (N = 242), but there is no such age
      pattern across female self-excluders (N = 63).

PMID- 24276576
TI  - Deathbed shock: causes and cures.

PMID- 24276577
TI  - Anthracene photodimerization in a bis-chromophoric hydrogen-bonding receptor.
AB  - The photochemistry and photophysics of a bis-anthracenyl hydrogen-bonding
      receptor (7-(3,5-bis((6-(4-(anthracen-9-yloxy) butanamido)pyridin-2
      yl)carbamoyl)phenylhept-6-ynoate, 2) were investigated in a fluid solution. At
      room temperature, fluorescence and intersystem crossing compete with
      intramolecular dimerization to form head-to-head and head-to-tail photoproducts,
      whereas fluorescence is the principal deactivation pathway at low temperature.
      Time-resolved fluorescence spectroscopy evidences two excimer-like emitting
      states whose sensitivity to quenching by oxygen is considerably lower than that
      of intramolecular photodimerization (K(SV) = ca. 450 vs. <100 L mol(-1),
      respectively). Based on the temperature-dependence and quenching efficiency of
      photodimerization, a mechanism is proposed in which the ground-state conformation
      of the tether controls the formation of the HH vs. HT photodimers via a non
      emissive intermediate.

PMID- 24276578
TI  - Longitudinal increase in anisometropia in older adults.
AB  - PURPOSE: Anisometropia shows an exponential increase in prevalence with
      increasing age based on cross-sectional studies. The purpose of this study was to
      evaluate longitudinal changes in anisometropia in all refractive components in
      older observers and to assess the influence of early cataract development.
      METHODS: Refractive error was assessed at two time points separated by
      approximately 12 years in 118 older observers (aged 67.1 and 79.3 years at the
      two test times). Anisometropia defined as greater than or equal to 1.00 D was
      calculated for all refractive components. The subjects had intact ocular lenses
      in both eyes throughout the study. Lens evaluations were performed at the second
      test using the Lens Opacities Classification System III. RESULTS: All refractive
      components approximately doubled in prevalence of anisometropia. Spherical
      equivalent anisometropia changed from 16.1 to 32.2%. Similar changes were found
      for spherical error (17 to 38.1%), primary astigmatism (7.6 to 17.8%), and
      oblique astigmatism (14.4 to 29.7%). Many who did not have anisometropia at the
      first visit subsequently developed anisometropia (e.g., 26.3% for spherical error
      and 22.9% for oblique cylinder). The onset of anisometropia occurred at all ages
      within the studied age range, with no particular preference for any one age. A
      small number lost anisometropia over time. Individual comparisons of refractive
      error changes in the two eyes in combination with nuclear lens changes showed
      that early changes in nuclear sclerosis in the two eyes could account for a large
      proportion of anisometropia (~40%), but unequal hyperopic shift in the spherical
      component in the two eyes was the primary cause of the anisometropia.
      CONCLUSIONS: Anisometropia is at least 10 times more common in the elderly than
      in children, and anisometropia develops in all refractive components in the
      oldest observers. Clinicians need to be aware of this common condition that could
      lead to binocular vision problems and potentially cause falls in the elderly.

PMID- 24276579
TI  - Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis
      inducing factor in non-small cell lung cancer.
AB  - Our previous study showed that patients with advanced stages of non-small cell
      lung cancer (NSCLC) were frequently detected with upregulation of hepatocyte
      growth factor (HGF). In vitro, HGF reduced expression of apoptosis-inducing
      factor (AIF) and cisplatin sensitivity in NSCLC cells. The effect of HGF was via
      HGF receptor (c-MET) and the downstream effector, focal adhesion kinase (FAK). In
      this study, we determined the prognostic value of AIF in NSCLC patients. AIF
      expression was determined by immunohistochemistry and immunoblotting. Our data
      show that AIF expression was associated with better prognosis. Expression of AIF
      inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol
      dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix
      metalloproteinase (MMP)-1, and HER2/neu, which were closely associated with drug
      resistance, tumor recurrence, metastasis and poor prognosis. Noteworthy, silence
      of HER2/neu gene expression increases AIF level and drug sensitivity. Addition of
      HGF inhibits AIF expression in HER2/neu-silenced cells. These results suggested
      that both HGF and HER2/neu affect drug resistance by regulating AIF expression in
      NSCLC.

PMID- 24276580
TI  - A 20-min nap in athletes changes subsequent sleep architecture but does not alter
      physical performances after normal sleep or 5-h phase-advance conditions.
AB  - PURPOSE: The aim of the study was to examine the effects of a post-prandial 20
      min nap on a short-term physical exercise and subsequent sleep in athletes
      keeping their usual sleep schedules and in 5-h phase-advance condition. METHODS:
      Sixteen healthy young male athletes (age 22.2 +/- 1.7 years, non-habitual
      nappers) participated in the study. After a baseline 8-h time in bed in normal
      and 5-h advanced sleep schedules, a standardized morning and lunch in a
      laboratory environment, subjects underwent either a nap (20 min of sleep elapsed
      from 3 epochs of stage 1 or 1 epoch of stage 2), or a rest without sleep by lying
      in a bed, between 13:00 and 14:00 hours in non-shifted condition or 08:00 and
      09:00 hours in shifted condition, after which anaerobic exercises were performed
      twice 2 h apart. Core body temperature was recorded throughout the study period.
      RESULTS: The nap extended sleep onset latency from 6.72 +/- 3.83 to 11.84 +/-
      13.44 min, after shifted condition but did not modify sleep architecture of the
      post-trial night among athletes, whether shifted or not. Moreover, napping did
      not improve physical performance but it delayed acrophase and batyphase of core
      body temperature rhythm parameters. CONCLUSION: Napping showed no reliable
      benefit on short-term performances of athletes exercising at local time or after
      a simulated jet lag.

PMID- 24276581
TI  - Streptomycin resistance is inherited as a recessive Mendelian trait in a
      Nicotiana sylvestris line.
AB  - The SR180 cell line has been isolated in a callus culture derived from a haploid
      Nicotiana sylvestris (n = X = 12) plant by its ability to proliferate on a
      selective medium containing 2,000 MUg/ml streptomycin sulphate. From the cell
      line diploid plants have been regenerated. The SR180 selfs are resistant to
      streptomycin. Streptomycin sensitivity in F1, and a 3?1 (sensitive to resistant)
      segregation in F2 indicate that resistance in the SR180 mutant is the result of a
      recessive Mendelian mutation. 

PMID- 24276582
TI  - Biochemical markers associated with two M(v) chromosomes from Aegilops ventricosa
      in wheat-Aegilops addition lines.
AB  - The distribution of three biochemical markers, U-1, CM-4 and Aphv-a, -b, among
      wheat-Aegilops addition lines carrying M(v) chromosomes from Aegilops ventricosa
      (genomes D(v)M(v)) has been investigated. Addition lines which had been
      previously grouped together on the basis of common non-biochemical characters
      carried marker U-1, a protein component from the 2M urea extract. The added
      chromosome, in the appropriate genetic background, seems to confer a high level
      of resistance to the eyespot disease, caused by the fungus Cercosporella
      herpotrichoides. The other two markers were concomitantly associated with another
      similarly formed group of addition lines. Both CM-4, a protein component from the
      chloroform:methanol extract, and Aphv-a, -b, alkaline phosphate isozymes, have
      been previously shown to be associated with homoeologous chromosome group 4,
      which suggests that the added chromosome in the second group of addition lines is
      4M(v). 

PMID- 24276583
TI  - D genome doners for Aegilops cylindrica (CCDD) and Triticum aestivum (AABBDD)
      deduced from esterase isozyme analysis.
AB  - Putative D genome donors for Aegilops cylindrica (2n = 28, CCDD) and Triticum
      aestivum (2n = 42, AABBDD) were studied with the isoelectric focusing patterns of
      esterase isozymes. 103 strains of Ae. cylindrica were uniform in their isozyme
      pattern. 30 strains of the putative parent, Ae. caudata, showed no zymogram
      variation, whereas the other parent, Ae. squarrosa, comprised 3 phenotypes.
      Natural Ae. cylindrica had an isozyme pattern which corresponded to a mixture of
      esterases from Ae. caudata and type 3 Ae. squarrosa. Therefore, it is concluded
      that the D genome donor of Ae. cylindrica is derived from type 3 Ae. squarrosa.
      These results suggest that Ae. cylindrica originated with a single amphiploidy
      event, and the C and D genomes have remained remarkably constant regarding
      esterase isozyme composition.On the other hand, T. aestivum comprised three
      zymogram phenotypes. These phenotypes contain bands which can be ascribed to the
      D genome of type 2 Ae. squarrosa. These results suggest that the D genome of Ae.
      cylindrica differs from that of T. aestivum. Evolution of the AB and D genomes of
      T. aestivum is indicated by the zymogram polymorphism. The origin of Ae.
      cylindrica is possibly more recent than that of T. aestivum. 

PMID- 24276584
TI  - Grain protein variability among species of Triticum and Aegilops: quantitative
      SDS-PAGE studies.
AB  - Total proteins were extracted from degermed seeds of various species of Triticum
      and Aegilops with solutions containing sodium dodecyl sulfate (SDS) and
      mercaptoethanol. The reduced, dissociated proteins were fractionated according to
      molecular weight (MW) by high-resolution polyacrylamide gel electrophoresis in
      buffers containing SDS (SDS-PAGE). Stained SDS-PAGE patterns were measured by
      densitometric scanning over a suitable range of optical density. The data were
      normalized to equivalent total areas for each of the densitometric scans by means
      of a computer program that also permitted the construction of patterns of
      hypothetical amphiploids by averaging patterns of two or three diploid species.
      The grain proteins of most species examined had distinctive qualitative and
      quantitative aspects that were characteristic of the species even though nearly
      every accession or cultivar of a species exhibited at least minor differences in
      pattern from other accessions or cultivars. The main protein components (probably
      prolamins) of Triticum monococcum ssp. monococcum, T. monococcum ssp. boeoticum,
      T. urartu, and Aegilops squarrosa had MW's in the range 29-36 X 10(3) whereas the
      most important components of Ae. speltoides, Ae. longissima, and Ae. searsii had
      MW's in the range 37-55 * 10(3). Changes in the quantitative expression of
      particular genes, especially those coding for storage protein components, may
      have been associated with speciation. The strong predominance of proteins with
      MW's in the range 29-36 * 10(3) in some accessions of AB genome tetraploids, such
      as T. turgidum ssp. dicoccoides, may indicate contributions to the B genome of
      these tetraploids by T. monococcum ssp. boeoticum, T. urartu, or Ae. squarrosa. 

PMID- 24276585
TI  - Hormone-induced caulogenesis in long-term tobacco cell lines and its effect on
      nuclear DNA content.
AB  - Manipulation of exogenous auxin and cytokinin levels during sequential subculture
      in vitro has been used to induce caulogenesis in several long-term tobacco cell
      lines. Concurrently, tissue samples at various stages of caulogenesis have been
      examined for nuclear DNA content. While a variety of hormone regimes permitted
      caulogenesis, extremely high (122.95 MUM) cytokinin levels and extremely low
      (0.285 MUM) auxin levels generally gave optimal response. For three lines,
      caulogenesis was accompanied by a progressive decrease in nuclear DNA content
      beyond that due to the loss of polyploid cells. In one line, however, DNA content
      remained stable during regeneration, perhaps reflecting the acquisition of a
      stably adapted aneuploid karyotype. Both caulogenic response and amount of
      nuclear DNA were affected by changes in the culture medium. The progressive
      nature of the observed changes in DNA content is inconsistent with a single-step
      selection for euploid competent cells. Alternative models postulating either
      progressive selection for euploidy, or the regulation of karyotype are proposed
      to explain the results. 

PMID- 24276586
TI  - Variations of chloroplast DNAs in the genus Pelargonium and their biparental
      inheritance.
AB  - The comparison of EcoRI patterns of chloroplast DNAs (ctDNAs) from five species
      of the genus Pelargonium and from 16 cultivars and varieties of Pelargonium
      zonale hort. demonstrates a remarkable inter- and intraspecific ctDNA (plastome)
      variation. The plastome of the P. zonale varieties could be differentiated into
      groups I, II and III. Reasons for this variation seem to be: occurrence of
      numerous spontaneous plastome mutations, intense hybridisation by gardeners and
      breeders, and biparental plastid inheritance.Crosses of P. zonale varieties with
      different ctDNA types lead to the direct evidence on the molecular level of
      biparental plastid inheritance and plastid sorting-out in F1-hybrids. 

PMID- 24276587
TI  - The mechanism of the mixed inheritance of chloroplast genes in Pelargonium :
      Evidence from gene frequency distributions among the progeny of crosses.
AB  - The distributions are given of gene frequencies among embryos after G X W and W X
      G plastid crosses within and between eight Pelargonium cultivars and some of
      their inbred or hybrid derivatives.Two distinct segregation patterns are
      recognized. Homozygous type I female parents (Pr1Pr1) have a high frequency of
      progeny with only maternal alleles, are intermediate for biparental and low for
      paternal offspring. Heterozygous type II female plants (Pr1Pr2) have an equally
      high frequency of maternal and paternal offspring and a generally low biparental
      frequency. These correspond to L-shaped and U-shaped gene frequency distributions
      respectively in which the only modes are at 0 per cent (maternal embryos) and 100
      per cent (paternal embryos), with no mode corresponding to the population mean
      and no sign of a Gaussian distribution.The extremely variable plastid gene
      frequencies are strongly influenced by the maternal nuclear genotype and by the
      plastid genotype in which the wild-type allele is always more successful than the
      mutant in strict comparisons.The relative frequencies of maternal and paternal
      zygotes, and the mean gene frequency among all the zygotes in a cross, are
      explicable in terms of the input frequencies of genes from the two parents, their
      degree of mixing, and by some form of selective replication of plastids. This
      selection is controlled by nuclear and plastid genotypes which may act in the
      same direction, to increase the frequency of either the maternal or the paternal
      alleles, or in opposition. But selection alone is inadequate to explain the
      shapes of the gene frequency distributions. Instead, a model is proposed in which
      the segregation or replication of plastids appears to have a strong random
      element, which results in random drift of gene frequencies within a heteroplasmic
      zygote or embryo. 

PMID- 24276588
TI  - Evaluation of an exotic maize population adapted to a locality.
AB  - An exotic Zea mays L. population ('Tuxpeno') was adapted to North Carolina
      conditions by first introducing genes for adaptability from two North Carolina
      varieties ([('Jarvis' X 'Indian Chief')'Tuxpeno']'Tuxpeno') including four
      generations of intermating, and then selecting for adaptability using maturity as
      the primary measure. The study evaluated selection for adaptability and the
      diversity available between adapted 'Tuxpeno' and the local varieties, 'Jarvis'
      and 'Indian Chief'. Analytical procedures were developed to quantify the
      diversity between populations and the complementation of local varieties by
      introduced germ plasms. The analyses utilized the specific effects available from
      the diallel mating design.Three replicate selections responded similarly under
      simple recurrent mass selection (1/10) for the earliest disease-free plants
      initially and additionally for plant types (primarily height) in the final
      generation. The 1/4 local germ plasm permitted rapid adaptation of 'Tuxpeno' gene
      pool to local conditions. The adapted 'Tuxpeno' populations yielded similarly to
      the local populations with an average heterosis for grain yield of 28% when
      crossed to the local populations used as source of genes for adaptability. The
      diversity found between adapted 'Tuxpeno' lines and these local varieties based
      on genes affecting grain yield was 1.5 to 2.5 times that measured between the
      local varieties ('Jarvis' and 'Indian Chief'). Diversity lost through
      intergradation with local material was a reasonable investment. Yield genes
      introduced from 'Tuxpeno' complemented local gene pools through nonadditive,
      primarily dominance-associated, gene effects. Reassortment of major gene blocks
      apparently occurred leading to significant divergence among replicate selections
      involving both additive-associated and dominance-associated gene effects. 

PMID- 24276589
TI  - Effect of neoadjuvant treatment in the management of osteosarcomas of the head
      and neck.
AB  - PURPOSE: Osteosarcomas of the craniomaxillofacial region in adults are rare
      malignant tumors with many sites of origin. The purpose of this study was to
      analyze the outcome of adult patients suffering from osteosarcomas and
      investigate whether neoadjuvant chemotherapy would be beneficial to overall
      outcome. PATIENTS AND METHODS: The medical records of 36 patients treated during
      2002-2012 were reviewed. All patients suffered from primary osteosarcomas of the
      craniomaxillofacial region. RESULTS: The mean survival of patients was 64.49 +/-
      23.52 months. The 2- and 5-year overall survival rates in the neoadjuvant
      treatment group were 100 and 66.7 %; in the surgery only group, the overall
      survival rates were 66.7 and 41.7 %, respectively. The neoadjuvant treatment (p =
      0.017), tumor size (p = 0.004), tumor location (p = 0.02), and age (p < 0.0001)
      were significant parameters influencing survival, whereas other tumor-related or
      demographic factors had no significant influence on survival. CONCLUSIONS: Early
      identification of osteosarcoma of the craniomaxillofacial region and combined
      treatment by neoadjuvant chemotherapy with radical surgery are the most important
      strategies in dealing with these sarcomas. If possible, this treatment option
      should be followed unless contraindicated by other factors.

PMID- 24276590
TI  - Expression of TGF-beta1, SNAI1 and MMP-9 is associated with lymph node metastasis
      in papillary thyroid carcinoma.
AB  - TGF-beta1, SNAI1 and MMP-9 are implicated in tumor invasion and metastasis. The
      purpose of this study was to examine TGF-beta1, SNAI1 and MMP-9 expression in
      papillary thyroid carcinoma (PTC), and to assess association of TGF-beta1, SNAI1
      and MMP-9 expression with several clinicopathological indicators of PTC. TGF
      beta1, SNAI1 and MMP-9 protein expression in 83 PTCs and their matched normal
      thyroid specimens were analyzed using immunohistochemistry. The mRNA expression
      levels of TGF-beta1, SNAI1 and MMP-9 in 12 fresh PTC specimens with lymph node
      metastasis (LNM), 12 fresh PTC specimens without LNM and their matched normal
      thyroid specimens were assessed by real-time RT-PCR. The results showed that the
      mRNA and protein expression levels of TGF-beta1, SNAI1 and MMP-9 were
      significantly higher in PTCs than in their matched normal thyroid tissues. There
      were not significant differences in TGF-beta1, SNAI1 and MMP-9 protein expression
      relative to age, gender, tumor size and TNM stage, except for MMP-9 whose protein
      expression correlated with tumor size. However, high mRNA and protein expression
      levels of TGF-beta1, SNAI1 and MMP-9 were significantly correlated with LNM.
      Furthermore, TGF-beta1, SNAI1 and MMP-9 protein expression were significantly
      correlated with one another. Concomitant expression of any two or all of the
      three molecules had stronger correlation with LNM than did each alone.
      Collectively, the present results indicate that immunohistochemical and real-time
      RT-PCR evaluation of TGF-beta1, SNAI1 and MMP-9 expression in PTC may be useful
      to predict the risk of LNM in PTC patients. 

PMID- 24276591
TI  - Identification of a gene for an ancient cytokine, interleukin 15-like, in
      mammals; interleukins 2 and 15 co-evolved with this third family member, all
      sharing binding motifs for IL-15Ralpha.
AB  - Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related
      cytokines with overlapping, yet also distinct functions, and established benefits
      for medical drug use. The present study identified a gene for an ancient third IL
      2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which
      hitherto was only reported in fish. IL-15L genes with intact open reading frames
      (ORFs) and evidence of transcription, and a recent past of purifying selection,
      were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL
      15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 %
      overall amino acid identity with IL-15, they share many of the IL-15 residues
      important for binding to receptor chain IL-15Ralpha, and recombinant bovine IL
      15L was shown to interact with IL-15Ralpha indeed. Comparison of sequence motifs
      indicates that capacity for binding IL-15Ralpha is an ancestral characteristic of
      the IL-2/15/15L family, in accordance with a recent study which showed that in
      fish both IL-2 and IL-15 can bind IL-15Ralpha. Evidence reveals that the species
      lineage leading to mammals started out with three similar cytokines IL-2, IL-15
      and IL-15L, and that later in evolution (1) IL-2 and IL-2Ralpha receptor chain
      acquired a new and specific binding mode and (2) IL-15L was lost in several but
      not all groups of mammals. The present study forms an important step forward in
      understanding this potent family of cytokines, and may help to improve future
      strategies for their application in veterinarian and human medicine. 

PMID- 24276592
TI  - Chemometric modeling of organic contaminant sources in surface waters of a
      mediterranean river basin.
AB  - Chemometric methods are applied to the analysis and interpretation of large
      multivariate datasets obtained in environmental monitoring studies.
      Concentrations of multiple organic compounds were measured in river samples taken
      from several sampling sites, at various geographical locations, during a number
      of campaigns and/or sampling time periods. Samples were collected and analyzed as
      part of an extensive multi-annual monitoring program from a mediterranean river
      basin (in Catalonia, at the northeast of Spain) by the Water Quality Regional
      Agency. Due to the great amount of multivariate data stored in environmental
      databases and to their complexity, chemometric modeling methods such as Principal
      Component Analysis (PCA) and Multivariate Curve Resolution with Alternating Least
      Squares (MCR-ALS) coupled with appropriate mapping representations are proposed
      for the evaluation of the environmental quality of the studied rivers. Results
      achieved in this study are intended to be a contribution to water quality
      assessment and evaluation of contamination of surface waters in river basins, and
      to support public policies of environmental control and management of the regions
      under study. 

PMID- 24276593
TI  - The relationship between hand function, depression, and the psychological impact
      of trauma in patients with traumatic hand injury.
AB  - The aim of this study was to investigate the acute-stage and later-stage impacts
      of trauma on a patient, and to determine the relationship between the degree of
      the impact of the event and recovery of hand function in patients with traumatic
      hand injury. The functional status of patients was assessed by the Disabilities
      of the Arm, Shoulder, and Hand (DASH) questionnaire; psychological influence was
      assessed by the Beck Depression Inventory (BDI); and the impact of the event was
      assessed by the Impact of Event Scale-Revised (IES-R) both during the acute stage
      and at a later stage. Fifty-four patients completed the study. The DASH, BDI, and
      IES-R scores were significantly improved at a later stage compared with the acute
      stage (P<0.05). The DASH, BDI, and IES-R scores had significant positive
      correlations with each other in both the acute stage and later stage (P<0.05). In
      the linear regression analysis, the independent variables affecting the DASH
      score at a later stage were the DASH and IES-R scores in the acute stage
      (P<0.05), whereas depression scores had no effect on functional outcome (P>0.05).
      Our study suggests that depression status, functional status of the hand, and
      impact of the event improve at a later stage, and that the functional outcome at
      a later stage is affected by the degree of impact of the event, and the
      functional status of the hand in the acute stage, in patients with traumatic hand
      injury. 

PMID- 24276596
TI  - The Wada test in the evaluation for epilepsy surgery.
AB  - The Wada test is the standard part of the pre-operative evaluation for epilepsy
      surgery. The procedure involves the slow injection of sodium amobarbital
      (typically 100-500mg) into the internal carotid artery following a transfermoral
      approach. The amobarbital anesthetizes the anterior two-thirds of the ipsilateral
      cerebral hemisphere for approximately 5-10 minutes. During this period of
      hemispheric anesthesia, assessment of expressive and receptive language can
      establish cerebral language representation. In addition, the procedure provides a
      reversible model to assess the risk of significant memory change following
      surgery. This is important because patients undergoing surgery involving the
      temporal lobe may experience significant memory decline following surgical
      resection of a temporal lobe seizure focus. This paper will represent information
      about the use of Wada testing, and discuss issues involved in establishing
      cerebral language representation, lateralization of temporal lobe dysfunction,
      seizure and memory outcome prediction, and future directions of this technique. 

PMID- 24276594
TI  - Maxillary distraction osteogenesis at Le Fort-I level induces bone apposition at
      infraorbital rim.
AB  - OBJECTIVE: The aim of this study is to evaluate whether there is any remodeling
      of bone at infraorbital rim following maxillary distraction osteogenesis (DO) at
      Le Fort-I level. MATERIALS AND METHODS: Twelve adult subjects in the age range of
      17-21 years with complete unilateral cleft lip and palate underwent advancement
      of the maxilla by DO. The effect of maxillary DO on the infraorbital rim
      remodeling was evaluated from lateral cephalograms recorded prior to the DO (T0),
      at the end of DO (T1), and at least 2-years after the DO (T2) by Walker's
      analysis. The ANOVA and two-tailed t test were used and probability value (P
      value) 0.05 was considered as statistically significant level. RESULTS: There was
      anterior movement of maxilla by 9.22 +/- 3.27 mm and 7.67 +/- 3.99 mm at the end
      of immediate (T1) and long-term (T2) follow-up of maxillary DO, respectively. The
      Walker's analysis showed 1.49 +/- 1.22 mm and 2.31 +/- 1.81 mm anterior movement
      of the infraorbital margin (Orbitale point) at the end of T1 and T2, respectively
      (P < 0.01). This apposition of bone at the infraorbital rim region further
      improved the facial profile of these patients. CONCLUSION: The advancement of
      maxilla by distraction osteogenesis at Le Fort-I level induced significant bone
      apposition at infraorbital rim. CLINICAL RELEVANCE: Patients with mild midface
      hypoplasia who would otherwise may be candidates for osteotomy at Le Fort-II or
      Le Fort-III level may benefit from maxillary distraction at Le Fort-I level.

PMID- 24276597
TI  - The shaken baby syndrome.
AB  - Trauma is the most common cause of death in childhood and non-accidental injury
      is the leading cause of death in infants between one month and one year of life.
      This is a newly emerging entity in Saudi Arabia. However, there is little
      available literature on the extent of child maltreatment in Saudi Arabia and
      other Arab countries. In this review, we will discuss various aspects of the
      central nervous system insults resulting from the inflicted trauma of child
      abuse. We aim to raise awareness in the region as the tragic loss of life and
      function is unequalled in childhood beyond the perinatal period. 

PMID- 24276598
TI  - Guillain-barre syndrome.
AB  - Guillain-Barre syndrome is an acute, or more often, a subacutely evolving
      paralytic disease of unestablished etiology. The condition is often designated as
      the Landy-Guillain-Strohl syndrome in recognition of the description provided by
      Landy in 1859 and again in 1916 by Guillain, Barre and Strohl. The pathogenesis
      and specific therapy in this condition remains imperfectly defined. The diagnosis
      is usually clinical with supportive laboratory tests. In this syllabus, we review
      the diagnostic criteria in Guillain-Barre syndrome and current therapies in the
      acute management followed by presentation of the acute management protocol used
      in the Neurosciences Department at the Riyadh Armed Forces Hospital. 

PMID- 24276599
TI  - Carpal Tunnel Syndrome in type 2 diabetic patients.
AB  - OBJECTIVE: To determine the frequency of carpal tunnel syndrome in type 2
      diabetic patients, its clinical profile and its other predisposing factors.
      METHODS: One hundred and forty six consecutive patients (57 male, 89 female) with
      type 2 diabetes mellitus seen in the diabetic clinic were examined prospectively
      and submitted to comprehensive electrophysiological studies to detect carpal
      tunnel syndrome and sensorimotor neuropathy. Those with carpal tunnel syndrome
      were compared to others to determine the additional predisposing factors for
      carpal tunnel syndrome in diabetic patients. RESULTS: The mean duration of
      diabetes was 11.5 years. Carpal tunnel syndrome was diagnosed in 39% of the
      patients (28% of the males and 46% of females). Numbness of the hands, Tinel's
      sign and Phalen's sign had poor sensitivity (61%, 54% and 37% respectively) but
      high specificity (75%, 85% and 91%). The main risk factor for carpal tunnel
      syndrome in diabetics was the duration of diabetes (p<0.001) and to a lesser
      degree female gender and obesity (p<0.05). CONCLUSION: Carpal tunnel syndrome is
      quite frequent in type 2 diabetic patients. Its clinical diagnosis may be
      difficult because of the poor sensitivity of its classical symptoms and signs. It
      should be suspected mainly in obese women with long-standing diabetes mellitus.
      Electrodiagnostic studies should be done in these patients because the earlier
      the diagnosis, the sooner consideration can be given to the need for surgical
      decompression.

PMID- 24276600
TI  - Clinical profile of Carpal Tunnel Syndrome in Oman.
AB  - OBJECTIVE: Carpal Tunnel Syndrome is the most common entrapment neuropathy with a
      reported incidence of 7 to 16% of the general population in Western studies.
      Since this has not been well studied in the Arabian peninsula, we studied 100
      patients with Carpal Tunnel Syndrome. METHODS: We studied 100 Omani patients with
      Carpal Tunnel Syndrome in our clinic. After clinical evaluation the diagnosis was
      confirmed by motor and sensory nerve conduction studies of the median and ulnar
      nerves. RESULTS: There were 15 males and 85 females. No systemic cause was
      identified in the majority of the patients. Involvement was unilateral in 23
      patients and bilateral in 77 patients. CONCLUSION: Carpel Tunnel Syndrome is
      common in Oman and can be easily diagnosed by clinical examination and nerve
      conduction studies. We found that the sensory symptoms often transgressed the
      median nerve distribution and tended to be bilateral for both sexes, with
      predominance for females.

PMID- 24276601
TI  - Cephalometric evaluation of craniofacial variation in normal Saudi population
      according to Steiner analysis.
AB  - OBJECTIVE: The objective of this study was to describe the craniofacial pattern
      of Saudi ethnic groups and to compare it with accepted standards for the
      Caucasian population according to Steiner analysis. METHODS: Lateral
      cephalometric radiographs of 87 Saudi students (74 male and 13 females) with
      balanced harmonious faces and clinically acceptable permanent occlusion, aged 21
      27 years old were used. A computer-aided cephalometric analysis was performed,
      and the mean values and standard deviations for the various cephalometric
      variables were obtained. RESULTS: A comparison of the results with the Steiner
      standards showed that the Saudis have relatively similar skeletal relationship
      and dentally there was a tendency toward bimaxillary protrusion. Further, there
      was a decrease in the lower facial height. CONCLUSION: It was evident that even
      in the Saudi ethnic groups with so-called well-balanced faces, there were some
      fundamental variations in the craniofacial structure of the Saudi Arab when
      compared with Steiner norms.

PMID- 24276602
TI  - Referral pattern of physical diseases in psychiatric in-patients.
AB  - OBJECTIVE: To study the referral pattern of physical diseases in psychiatric in
      patients in a university teaching general hospital. METHODS: A longitudinal
      prospective study, over 12 months with a consecutive series of referrals from
      psychiatric in-patient unit to other specialties, in King Khalid University
      Hospital, using a predesigned format that included information on age, sex,
      physical examination on admission, consulted medical specialties and opinion of
      the consulted physician. RESULTS: Referral rate was 38% of the total psychiatric
      in-patients. The most common consulted specialties were endocrinology (14.5%),
      dermatology (12.5%) and cardiology (12%). About three quarters of the patients
      were below 30 years of age. Physical examination on admission was not carried out
      for 16% of cases. Forty-four percent of clinicians responses were within 48 hours
      of the consultation. There were no responses in 12% of the consultations and no
      life-threatening physical conditions. About one-third of referred patients were
      schizophrenics. CONCLUSION: Physical diseases in psychiatric in-patients are
      common. Evaluation of psychiatric patients should include a detailed physical
      examination, thorough medical and psychiatric history, as well as appropriate
      laboratory testing. Improving psychiatrist trainees' skills in detecting and
      assessing physical conditions in psychiatric patients is essential.

PMID- 24276603
TI  - The pattern of hearing impairment among schoolboys in an Institute for deaf
      subjects.
AB  - OBJECTIVE: The aim of this study was to study the pattern of deafness among boys
      of Al-Amal Institutes for the Deaf in Abha, the capital city of Asir Region,
      Southwestern Saudi Arabia. METHODS: All students (n=155) were subjected to full
      otoscopic and audiometric examinations, and the type and degree of deafness were
      graded according to the recommendation of the British Society of Audiology.
      Computerized tomography scan was carried out to exclude congenital inner ear
      deformity, and specific Igm antibodies assay for TORCHS was carried out when the
      history of intrauterine infection was positive or suggestive. RESULTS: More than
      97% of students had sensori-neural hearing loss of various grades (55% profound,
      28% severe and 14.5% moderate), while congenital conductive deafness constituted
      3% of all cases. Residual hearing was reported for 43% of cases. There was
      delayed identification of deafness with an inverse relation between the age of
      identification of deafness and its severity (F = 227.66, P < 0.001). Prematurity
      (30%), intrauterine infection (17%) and heredity (15.5%) were the most frequently
      encountered causes of deafness. Postnatal causes accounted for only 20%, mostly
      due to meningitis 12%, other childhood fevers 5% and trauma 2.5%. Deafness of
      unknown cause constituted 12% of all cases. CONCLUSION: The preventable causes of
      deafness in the region has not yet been overcome, a finding that will necessitate
      more efforts to upgrade the prenatal and perinatal health care. Late
      identification of hearing impairment will make the improvement in the audiology
      screening for infants the priority need.

PMID- 24276604
TI  - A pilot study of the relationship between Down's syndrome and hearing loss.
AB  - OBJECTIVE: Hearing loss is one of the most common disabilities in children with
      Down's syndrome. The objective of this study is to investigate the incidence and
      types of hearing loss in Down's syndrome patients. METHODS: Twenty-six subjects
      with Down's syndrome aged between 2 and 17 year old were evaluated during the
      year 1998, referred randomly by the Pediatric Department and the Down's Syndrome
      Centre. Screening audiological procedures were used to evaluate these patients,
      which include behavioral audiometry, play and pure tone audiometry, tympanometry
      and ABR, which is the measurement of the activity of the auditory pathway
      structures from the distal auditory nerve to the midbrain using clicks or
      tonepips. RESULTS: The study showed that 35% were found to have normal hearing
      compared to 4% found to have sensorineural hearing loss, while the majority of
      patients were found to have a conductive hearing loss (50%). CONCLUSION: Hearing
      evaluation of children with Down's syndrome revealed a high prevalence of
      conductive hearing loss. This study proposed that this might be attributed to
      eustachian tube dysfunction and middle ear ciliary malfunction. Further
      diagnostic studies need to be carried out.

PMID- 24276605
TI  - Asperger's syndrome.
AB  - This study presents a 14-year-old Saudi child with poor school achievement,
      diagnosed by psychiatrists as mentally retardated with a significant social
      deficit. No neurological disorder was evident. She has high to very high
      intellectual abilities on testing her intelligence quotient. Her verbal learning
      ability was also very high. Her social skills and capacity were impaired. No
      evidence of poor language was detected. The patient is diagnosed as suffering
      from Asperger's syndrome, and not mentally retarded. She has the criteria for
      Asperger's syndrome according to Diagnositic and Statistical Manual, 4th edition,
      including the significant social deficit with normal intellectual functioning.
      The utility of such a diagnosis is briefly discussed. 

PMID- 24276606
TI  - Ankylosing spondylitis presenting with discitis.
AB  - Ankylosing spondylitis is not an uncommon disease worldwide, yet is relatively
      rare in Bahrain. There is a typical pattern of joint involvement in cases of
      ankylosing spondylitis, but the presentation of discitis is rare. We present a
      case of a patient presenting with backache and was diagnosed to have discitis.
      The diagnosis of ankylosing spondylitis was made only after he was found to be
      Human Leukocyte Antigen-827 positive. This is the first case report of ankylosing
      spondylitis presenting as discitis in Bahrain. 

PMID- 24276607
TI  - Post carotid endarterectomy seizure.
AB  - Post carotid endarterectomy seizure is a known clinical presentation in patients
      who suffer from hyperperfusion syndrome. This case focuses on the importance of
      identification of high risk patients for developing this syndrome and delaying
      their discharge from the hospital after successful carotid endarterectomy. 

PMID- 24276609
TI  - Resident's perspective of neurology training in the Kingdom.

PMID- 24276608
TI  - Hypertensive encephalopathy after successful treatment of eclampsia.
AB  - The association between acute rise of blood pressure and encephalopathy with
      early recognition, and therapy reversibility has been reported. We reported a
      case of a young lady in postnatal period, presented with acute rise of blood
      pressure, encephalopathy, quadriparesis, and apraxia. Magnetic resonance imaging
      of the brain showed hyperintense lesions in occipital, parietal and right
      temporal areas. Cerebral angio showed multiple segmental vasoconstriction and
      narrowing of intracerebral vessels. Immediate control of blood pressure enhanced
      recovery but it is incomplete. 

PMID- 24276610
TI  - Folate deficiencyy and neurologic complications in elderly Omani patients.

PMID- 24276611
TI  - Radiology quiz.

PMID- 24276612
TI  - Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed
      CaC6.
AB  - Pressure can tune material's electronic properties and control its quantum state,
      making some systems present disconnected superconducting region as observed in
      iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (Tc of
      11.5 K), applying pressure first Tc increases and then suppresses and the
      superconductivity of this compound is eventually disappeared at about 18 GPa.
      Here, we report a theoretical finding of the re-emergence of superconductivity in
      heavily compressed CaC6. The predicted phase III (space group Pmmn) with
      formation of carbon nanofoam is found to be stable at wide pressure range with a
      Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase
      IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior,
      indicating again departure from superconductivity. Re-emerged superconductivity
      in compressed CaC6 paves a new way to design new-type superconductor by inserting
      metal into nanoporous host lattice.

PMID- 24276613
TI  - Monitoring differentiated thyroid cancer patients with negative serum
      thyroglobulin. Diagnostic implication of TSH-stimulated antithyroglobulin
      antibody.
AB  - AIM: Serum antithyroglobulin antibody (TgAb) has been reported as a surrogate
      marker for differentiated thyroid cancer (DTC) in some conditions. We
      investigated changes in serum TgAb levels after stimulation with thyroid
      stimulating hormone (TSH) and the clinical implications for monitoring DTC.
      PATIENTS, METHODS: We retrospectively enrolled 53 DTC patients who had undergone
      total thyroidectomy and were negative for serum Tg and positive for TgAb.
      Patients underwent high-dose radioactive iodine treatment, and serum TgAb was
      measured before (TgAbBAS) and after TSH stimulation (TgAbSTIM). TgAb was followed
      up 6 to 12 months later (TgAbF/U). The change in TgAb after TSH stimulation
      (?TgAbSTIM) was calculated as a percentage of the baseline level. Patient disease
      status was classified into no residual disease (ND) and residual or recurred
      disease (RD) by follow-up imaging studies and pathologic data. The
      characteristics and diagnostic value of serum TgAb levels and ? TgAbSTIM were
      investigated with respect to disease status. RESULTS: 38 patients were in the ND
      group and 15 were in the RD group. TgAbBAS, TgAbSTIM and TgAbF/U were
      significantly higher in the RD compared to the ND group (p = 0.0008, 0.0002, and
      < 0.0001, respectively). ?TgAbSTIM was also significantly higher in the RD group
      (p = 0.0009). In the patients who presented with obviously high (>= 50%) or low
      (< -50%) ? TgAbSTIM, the proportions in the RD group were markedly different at
      100% and 7%, respectively. ? TgAbSTIM had significant diagnostic value for RD (p
      < 0.001). CONCLUSION: The change in serum TgAb level after TSH stimulation is
      different between the RD and ND groups, and thus, it may be used as a surrogate
      diagnostic marker for DTC when the serum Tg is negative and TgAb is positive.

PMID- 24276614
TI  - Chest pain in acute myocardial infarction: are men from Mars and women from
      Venus?

PMID- 24276615
TI  - Peroxisome proliferator-activated receptor gamma ligand troglitazone and TRAIL
      synergistically induce apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to cause
      apoptosis in several types of malignant tumor cells through its interaction with
      the death domain-containing receptor, death receptor 5 (DR5). In the present
      study, we showed that co-treatment with troglitazone (TGZ), a synthetic ligand of
      peroxisome proliferator-activated receptor gamma (PPARgamma), and TRAIL
      synergistically induced apoptosis through DR5 upregulation in human colon cancer
      DLD-1 cells. TGZ elevated DR5 expression at the promoter level through the
      CCAAT/enhancer-binding protein homologous protein (CHOP) binding site. These
      results suggest that combined treatment with TGZ and TRAIL may be promising as a
      new therapy against malignant tumors.

PMID- 24276616
TI  - Investigating the hydrogen-bond acceptor site of the nicotinic pharmacophore
      model: a computational and experimental study using epibatidine-related molecular
      probes.
AB  - The binding mode of nicotinic agonists has been thoroughly investigated in the
      last decades. It is now accepted that the charged amino group is bound by a
      cation-pi interaction to a conserved tryptophan residue, and that the aromatic
      moiety is projected into a hydrophobic pocket deeply located inside the binding
      cleft. A hydrogen bond donor/acceptor, maybe a water molecule solvating this
      receptor subsite, contributes to further stabilize the nicotinic ligands. The
      position of this water molecule has been established by several X-ray structures
      of the acetylcholine-binding protein. In this study, we computationally analyzed
      the role of this water molecule as a putative hydrogen bond donor/acceptor moiety
      in the agonist binding site of the three most relevant heteromeric (alpha4beta2,
      alpha3beta4) and homomeric (alpha7) neuronal nicotinic acetylcholine receptor
      (nAChR) subtypes. Our theoretical investigation made use of epibatidine 1 and
      deschloroepibatidine 2 as molecular probes, and was then extended to their
      analogues 3 and 4, which were subsequently synthesized and tested at the three
      target receptor subtypes. Although the pharmacological data for the new ligands 3
      and 4 indicated a reduction of the affinity at the studied nAChRs with respect to
      reference agonists, a variation of the selectivity profile was clearly evidenced.

PMID- 24276617
TI  - The Peru Cervical Cancer Screening Study (PERCAPS): the design and implementation
      of a mother/daughter screen, treat, and vaccinate program in the Peruvian jungle.
AB  - Peru struggles to prevent cervical cancer (CC). In the jungle, prevention
      programs suffer from significant barriers although technology exists to detect CC
      precursors. This study used community based participatory research (CBPR) methods
      to overcome barriers. The objective was to evaluate the utility of CBPR
      techniques in a mother-child screen/treat and vaccinate program for CC prevention
      in the Peruvian jungle. The CC prevention program used self-sampling for human
      papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine
      Gardasil for vaccination. Community health leaders (HL) from around Iquitos
      participated in a two half day educational course. The HLs then decided how to
      implement interventions in their villages or urban sectors. The success of the
      program was measured by: (1) ability of the HLs to determine an implementation
      plan, (2) proper use of research forms, (3) participation and retention rates,
      and (4) participants' satisfaction. HLs successfully registered 320 women at soup
      kitchens, schools, and health posts. Screening, treatment, and vaccination were
      successfully carried out using forms for registration, consent, and results with
      minimum error. In the screen/treat intervention 100% of participants gave an HPV
      sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and
      57% returned for 6-month followup. Vaccine intervention: 98% of girls received
      the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques
      successfully helped implement a screen/treat and vaccinate CC prevention program
      around Iquitos, Peru. These techniques may be appropriate for large-scale
      preventive health-care interventions.

PMID- 24276619
TI  - Unraveling the efficient applications of secondary metabolites of various
      Trichoderma spp.
AB  - Recent shift in trends of agricultural practices from application of synthetic
      fertilizers and pesticides to organic farming has brought into focus the use of
      microorganisms that carryout analogous function. Trichoderma spp. is one of the
      most popular genera of fungi commercially available as a plant growth promoting
      fungus (PGPF) and biological control agent. Exploitation of the diverse nature of
      secondary metabolites produced by different species of Trichoderma augments their
      extensive utility in agriculture and related industries. As a result, Trichoderma
      has achieved significant success as a powerful biocontrol agent at global level.
      The endorsement of Trichoderma spp. by scientific community is based on the
      understanding of its mechanisms of action against a large set of fungal,
      bacterial and in certain cases viral infections. However, it is still an agnostic
      view that there could be any single major mode of operation, although it is
      argued that all mechanisms operate simultaneously in a synchronized fashion. The
      central idea behind this review article is to emphasize the potentiality of
      applications of target specific secondary metabolites of Trichoderma for
      controlling phytopathogens as a substitute of commercially available whole
      organism formulations. With the aim to this point, we have compiled an inclusive
      list of secondary metabolites produced by different species of Trichoderma and
      their applications in diverse areas with the major emphasis on agriculture.
      Outlining the importance and diverse activities of secondary metabolites of
      Trichoderma besides its relevance to agriculture would generate greater
      understanding of their other important and beneficial applications apart from
      target specific biopesticides. 

PMID- 24276618
TI  - Ethnic disparities in the association of body mass index with the risk of
      hypertension and diabetes.
AB  - Despite having lower body mass index (BMI) compared to other ethnic groups,
      Asians continue to develop significant metabolic diseases such as hypertension
      and diabetes. To evaluate the disparate association of BMI and risk of
      hypertension and diabetes in Asians. We retrospectively studied 150,753 adults
      from the 1985-2011 California Behavioral Risk Factor Survey. Trends in prevalence
      of obesity, hypertension, and diabetes were stratified by ethnicity. Multivariate
      logistic regression models evaluated the incremental effect of one unit BMI
      increase on risk of hypertension and diabetes and the disparate risks of
      hypertension and diabetes at different BMI thresholds. Asians had the lowest BMI
      among all groups. However, the impact of increasing BMI on risk of hypertension
      and diabetes was significantly greater in Asians. For each one unit increase in
      BMI, Asians were significantly more likely to have hypertension (OR 1.15; 95% CI
      1.13-1.18) compared to non-Hispanic whites, blacks, and Hispanics. Similar trends
      were seen for diabetes (Asians: OR 1.15; 95% CI 1.13-1.18). The risk of
      hypertension in Asians with BMI >= 22 was similar to non-Hispanic whites with BMI
      >= 27 and blacks with BMI >= 28. The risk of diabetes in Asians with BMI >= 28
      was similar to non-Hispanic whites with BMI >= 30. Despite lower overall BMI
      compared to other groups, weight gain in Asians is associated with significantly
      higher risks of hypertension and diabetes. Compared to other ethnic groups,
      similar risks of hypertension and diabetes are seen in Asians at much lower BMI.

PMID- 24276620
TI  - Tumor necrosis therapy antibody interleukin-2 fusion protein elicits prolonged
      and targeted antitumor effects in vivo.
AB  - Interleukin-2 (IL-2) is one of the most successful cytokines applied in tumor
      immunotherapy because of its ability to stimulate potent cellular immune
      response. The life-threatening toxicity of vascular leak syndrome (VLS)
      associated with the high-dose IL-2 treatment regimen has limited its use in tumor
      immunotherapy. To reverse this situation, a tumor-targeted fusion protein,
      recombinant human TNT-IL2 (rhTNT-IL2), was generated with both the cytokine
      activity of IL-2 and the tumor-targeting ability of TNT antibody. TNT is a human
      tumor necrosis therapy monoclonal antibody capable of binding intracellular
      antigens which are accessible and abundant in necrotic regions of tumors. The
      immunotherapeutic potential of this fusion protein was tested in murine melanoma
      and lung cancer models, and tumor-bearing mice showed satisfied tumor regressions
      after rhTNT-IL2 immunotherapy. Immunohistochemical study showed a distinct
      penetration of IL-2 in tumors in mice treated with rhTNT-IL2, indicating its
      evident tumor-targeting activity. Moreover, the rhTNT-IL2 was well tolerated in
      cynomolgus monkeys in a 12-week long-term repeated toxicity study. These studies
      indicate that the targeting of IL-2 to necrotic areas of tumors might be a new
      approach for the immunotherapy of solid tumors. 

PMID- 24276621
TI  - Engineering the alpha-ketoglutarate overproduction from raw glycerol by
      overexpression of the genes encoding NADP+-dependent isocitrate dehydrogenase and
      pyruvate carboxylase in Yarrowia lipolytica.
AB  - To establish and develop a biotechnological process of alpha-ketoglutaric acid
      (KGA) production by Yarrowia lipolytica, it is necessary to increase the KGA
      productivity and to reduce the amounts of by-products, e.g. pyruvic acid (PA) as
      major by-product and fumarate, malate and succinate as minor by-products. The aim
      of this study was the improvement of KGA overproduction with Y. lipolytica by a
      gene dose-dependent overexpression of genes encoding NADP(+)-dependent isocitrate
      dehydrogenase (IDP1) and pyruvate carboxylase (PYC1) under KGA production
      conditions from the renewable carbon source raw glycerol. Recombinant Y.
      lipolytica strains were constructed, which harbour multiple copies of the
      respective IDP1, PYC1 or IDP1 and PYC1 genes together. We demonstrated that a
      selective increase in IDP activity in IDP1 multicopy transformants changes the
      produced amount of KGA. Overexpression of the gene IDP1 in combination with PYC1
      had the strongest effect on increasing the amount of secreted KGA. About 19% more
      KGA compared to strain H355 was produced in bioreactor experiments with raw
      glycerol as carbon source. The applied cultivation conditions with this strain
      significantly reduced the main by-product PA and increased the KGA selectivity to
      more than 95% producing up to 186 g l(-1) KGA. This proved the high potential of
      this multicopy transformant for developing a biotechnological KGA production
      process.

PMID- 24276622
TI  - Engineering pyruvate decarboxylase-mediated ethanol production in the
      thermophilic host Geobacillus thermoglucosidasius.
AB  - This study reports the expression, purification, and kinetic characterization of
      a pyruvate decarboxylase (PDC) from Gluconobacter oxydans. Kinetic analyses
      showed the enzyme to have high affinity for pyruvate (120 MUM at pH 5), high
      catalytic efficiency (4.75 * 10(5) M(-1) s(-1) at pH 5), a pHopt of approximately
      4.5 and an in vitro temperature optimum at approximately 55  degrees C. Due to in
      vitro thermostablity (approximately 40 % enzyme activity retained after 30 min at
      65  degrees C), this PDC was considered to be a suitable candidate for
      heterologous expression in the thermophile Geobacillus thermoglucosidasius for
      ethanol production. Initial studies using a variety of methods failed to detect
      activity at any growth temperature (45-55  degrees C). However, the application
      of codon harmonization (i.e., mimicry of the heterogeneous host's transcription
      and translational rhythm) yielded a protein that was fully functional in the
      thermophilic strain at 45  degrees C (as determined by enzyme activity, Western
      blot, mRNA detection, and ethanol productivity). Here, we describe the first
      successful expression of PDC in a true thermophile. Yields as high as 0.35 +/-
      0.04 g/g ethanol per gram of glucose consumed were detected, highly competitive
      to those reported in ethanologenic thermophilic mutants. Although activities
      could not be detected at temperatures approaching the growth optimum for the
      strain, this study highlights the possibility that previously unsuccessful
      expression of pdcs in Geobacillus spp. may be the result of ineffective
      transcription/translation coupling.

PMID- 24276623
TI  - A novel class of fungal lipoxygenases.
AB  - Lipoxygenases (LOXs) are well-studied enzymes in plants and mammals. However,
      fungal LOXs are less studied. In this study, we have compared fungal LOX protein
      sequences to all known characterized LOXs. For this, a script was written using
      Shell commands to extract sequences from the NCBI database and to align the
      sequences obtained using Multiple Sequence Comparison by Log-Expectation. We
      constructed a phylogenetic tree with the use of Quicktree to visualize the
      relation of fungal LOXs towards other LOXs. These sequences were analyzed with
      respect to the signal sequence, C-terminal amino acid, the stereochemistry of the
      formed oxylipin, and the metal ion cofactor usage. This study shows fungal LOXs
      are divided into two groups, the Ile- and the Val-groups. The Ile-group has a
      conserved WRYAK sequence that appears to be characteristic for fungal LOXs and
      has as a C-terminal amino acid Ile. The Val-group has a highly conserved WL-L/F
      AK sequence that is also found in LOXs of plant and animal origin. We found that
      fungal LOXs with this conserved sequence have a Val at the C-terminus in contrast
      to other LOXs of fungal origin. Also, these LOXs have signal sequences implying
      these LOXs will be expressed extracellularly. Our results show that in this
      group, in addition to the Gaeumannomyces graminis and the Magnaporthe salvinii
      LOXs, the Aspergillus fumigatus LOX uses manganese as a cofactor. 

PMID- 24276625
TI  - Cross-incompatibility between two sympatric polyploid Solanum species.
AB  - Preliminary results from a large number of reciprocal crosses between the closely
      related sympatric species S. gourlayi Hawkes (2n=4x=48) and S. oplocense Hawkes
      (2n=6x=72) indicated that they are difficult to hybridize. Pollen-pistil
      incompatibility barriers were detected via fluorescent microscopy. The cross
      incompatibility reaction occurred at three sites in 6x*4x crosses; on the stigma,
      in the first one-third of the style, and in the first two-thirds of the style. In
      the reciprocal 4x*6x crosses the incompatibility reaction invariably occurred in
      the ovary. Backcrosses of interspecific pentaploid hybrids (that were
      occasionally formed) to both parental populations were fully compatible,
      partially compatible, and fully incompatible with three sites of cross
      incompatibility reaction similar to those observed in 6x*4x crosses,
      respectively. Both polyploid species were found to be selfcompatible, whereas
      their F1 hybrids were found to be self-incompatible. An hypothesis based on
      interactions of dominant cross-incompatibility (CI) genes in pistils and dominant
      specific complementary genes in pollen grains is postulated to explain these
      observations. The cross-incompatibility system that appears to be operating in
      nature between 4x S. gourlayi and 6x S. oplocense provides a way for gene
      exchange between sympatric populations without threatening the identity of either
      species. 

PMID- 24276624
TI  - Theory and experiment on particle trapping and manipulation via optothermally
      generated bubbles.
AB  - We present a theoretical analysis and experimental demonstration of particle
      trapping and manipulation around optothermally generated bubbles. We show that a
      particle located within 500 MUm of a surface bubble can be attracted towards a
      bubble by drag force resulting from a convective flow. Once the particle comes in
      contact with the bubble's surface, a balance between surface tension forces and
      pressure forces traps the particle on the bubble surface, allowing the particle
      to move with the bubble without detaching. The proposed mechanism is confirmed by
      computational fluid dynamics simulations, force calculations, and experiments.
      Based on this mechanism, we experimentally demonstrated a novel approach for
      manipulating microparticles via optothermally generated bubbles. Using this
      approach, randomly distributed microparticles were effectively collected and
      carried to predefined locations. Single particles were also manipulated along
      prescribed trajectories. This bubble-based particle trapping and manipulation
      technique can be useful in applications such as micro assembly, particle
      concentration, and high-precision particle separation. 

PMID- 24276626
TI  - Genetics of the peroxidase isoenzymes in Petunia : Part 1: organ specificity and
      general genetic aspects of the peroxidase isoenzymes.
AB  - The peroxidase system in Petunia can be separated into a considerable number of
      bands by starch gel electrophoresis. The electrophoretic pattern obtained is not
      only dependent on the genotype of the plant but also on the organ investigated,
      the state of development of that organ, and the age of the plant. Several
      structural and regulatory genes seem to be involved in the production of the
      peroxidase isoenzymes. In Petunia at least three structural genes can be
      distinguished by their independent segregation. It is suggested that a few more
      structural genes code for the peroxidase isoenzymes in Petunia. In addition, post
      transcriptional modification may contribute to the number of peroxidase
      isoenzymes. 

PMID- 24276627
TI  - Float culture of wheat anthers.
AB  - Experiments on wheat anther culture in liquid media either synthetic or with
      potato extract show that it is possible to obtain as many embryos as when using
      solid potato extract medium. In liquid media young embryos or 14-day old induced
      anthers can differentiate green plants for regeneration. Glutamine is effective
      in culturing anthers and can replace potato extract in the medium. 

PMID- 24276628
TI  - The role of 'Norin 10' dwarfing genes in photosynthetic and respiratory activity
      of wheat leaves.
AB  - A comparative analysis of eight cultivars of spring wheat (Triticum aestivum)
      classified by height as tall (T), semi-dwarf (D1), dwarf (D2) and very dwarf (D3)
      was conducted to study their efficiency of oxygen exchange during photosynthesis
      and dark respiration. Two cultivars were included in each height group.Cultivars
      carrying 'Norin 10' dwarfing genes (D1, D2 and D3) were found to have a
      significantly higher photosynthetic rate per unit leaf area than talls (T) that
      lack these genes. Among the 'Norin' gene carriers, dwarf group (D2) was most
      efficient, followed by very dwarf (D3) and semi-dwarf (D1).Photosynthetic rate
      and respiratory rate were found to have a positive relationship. 

PMID- 24276629
TI  - Observed and hypothetical leaf rust progress curves of some genotypes of wheat.
AB  - The hypothetical leaf rust progress curves of 15 genotypes of wheat were
      generated by integrating the components of slow rusting resistance determined in
      the glasshouse. The area under the disease progress curve (AUDPC) from the
      hypothetical and observed leaf rust progress curves were compared. It was found
      that the hypothetical AUDPC values of all the genotypes studied were smaller than
      their respective observed AUDPC values. Possible causes for the discrepancies in
      the observed and hypothetical values are discussed. 

PMID- 24276630
TI  - In vitro propagation and chromosome doubling of a Triticum crassum x Hordeum
      vulgare intergeneric hybrid.
AB  - In vitro culture of inflorescence tissue of a Triticum crassum (6x) x Hordeum
      vulgare cv. 'Bomi' (2x) intergeneric hybrid resulted in the proliferation of
      totipotent callus from which plants were regenerated. Regeneration was also
      achieved from immature inflorescence callus of T. crassum but not from H.
      vulgare. T. crassum x H. vulgare regenerates had a somatic chromosome number of
      28, identical to that of the original hybrid. Four chimeric plants with a
      partially doubled chromosome number were obtained by in vitro colchicine
      treatment of hybrid callus prior to induction of plant regeneration. All T.
      crassum regenerates had 35 chromosomes rather than the expected number of 42.
      Meiotic analysis of a 35-chromosome plant revealed an extremely abnormal meiosis
      which might be attributable to a complete disturbance in meiotic control
      system(s) including that of meiotic pairing. 

PMID- 24276631
TI  - A remark on the notions of gene and gametic frequencies for sex-linked genes.
AB  - A general model describing the evolution of genotypic frequencies at a
      heterosomal locus with n alleles is introduced. The treatment includes as a
      special case the standard derivation for X-linked loci as well as different
      concepts encountered in the literature which seem to contradict this derivation.
      The disagreement, however, is easily solved by distinguishing between gene and
      gametic frequencies. 

PMID- 24276632
TI  - Chinese hamster x American mink somatic cell hybrids: characterization of a clone
      panel and assignment of the mink genes for malate dehydrogenase, NADP-1 and
      malate dehydrogenase, NAD-1.
AB  - Chinese hamster x American mink somatic cell hybrids were obtained and examined
      for chromosome content and expression of mink malate dehydrogenase, NADP (MOD-1;
      EC 1.1.1.40), malate dehydrogenase, NAD (MOR-1; EC 1.1.1.37), glucose-6-phosphate
      dehydrogenase (G6PD; EC 1.1.1.49) and hypoxanthine phosphoribosyltransferase
      (HPRT; EC 2.4.2.8). All the hybrid clones examined were found to segregate mink
      chromosomes. A clone panel containing 25 clones was set up. The possibilities and
      limitations of this panel for mink gene mapping are analysed. Using this panel,
      it is feasible to rapidly map genes located on chromosomes 1-13 and to
      provisionally assign genes located on chromosome 14 and the X. Based on the data
      obtained, the genes for MOD-1 and MOR-1 were firmly assigned to mink chromosomes
      1 and 11, respectively, and the genes for G6PD and HPRT were provisionally
      assigned to the X. 

PMID- 24276633
TI  - MDH-polymorphism in Drosophila subobscura: I. Selection and hitch-hiking in
      laboratory populations.
AB  - The interrelation of genic polymorphism at the Malate dehydrogenase (Mdh)-locus
      and chromosomal polymorphism for superimposed gene arrangements was studied in 5
      experimental populations of Drosophila subobscura. It could be shown that
      chromosomal polymorphism is maintained by balancing selection in favour of the
      heterozygotes. In contrast, selection at the Mdh-locus itself seems to be of
      minor importance. The changes of frequency observed for the Mdh-alleles are most
      probably due to hitch-hiking on the gene blocks enclosed by the chromosomal
      structures or to selection for tightly linked genes rather than to fitness
      differences between Mdh-genotypes. The results may be considered as a model for
      the situation found in natural populations of D. subobscura. 

PMID- 24276634
TI  - Esterase genes in Daphnia pulex: linked inheritance and genotypic distribution in
      natural populations.
AB  - Esterase patterns were examined in three populations of Daphnia pulex. The total
      number of bands showing esterase activity was 17. Three major genes Est-1, Est-2,
      Est-3 controlling esterase synthesis were identified and genetically studied.
      These genes were found to be located in the same linkage group. It was shown that
      two or three homologous chromosomes differing in sets of esterase alleles
      predominantly occur in the populations considered. 

PMID- 24276635
TI  - Successful crosses between Festuca arundinacea Schreb. and Dactylis glomerata L.
AB  - Five F1 plants have been obtained after extensive crossing between different
      ecotypes or varieties of Festuca arundinacea Schreb. and Dactylis glomerata L.
      The success did not appear to depend on specific treatments (spraying with
      epsilon-aminocaproic acid or gibberellic acid or pre-pollination with killed
      pollen from the seed parent), but the crossability is limited to exceptional
      plants.F1 hybrids showed characteristics of both the parents. In four hybrids
      various developmental disturbances were observed (low viability, aneusomaty,
      absence of development of inflorescences). Only one hybrid consistently showed
      2n=35 chromosomes, good viability and growth, however, it was sterile. After
      clonal propagation, attempts for polyploidization were started. 

PMID- 24276636
TI  - The genetical expectations of doubled haploid lines derived from different filial
      generations.
AB  - The genetical expectations of the means, variances and covariances of populations
      of doubled haploid lines derived from f1, F2, F3 and intermated F2 (S3)
      generations are presented. These expectations are identical, regardless of
      genetical architecture, providing there is no linkage disequilibrium. In the
      presence of linkage disequilibrium differences will occur whose magnitude and
      direction will depend on the degree of disequilibrium, recombination frequency
      and the presence or absence of epistasis.Data from an experiment to detect
      linkage disequilibrium in a cross between two spring barley varieties are
      presented. This involved a comparison of means, variances and covariances of
      doubled haploid populations derived from the F1 and F2 generations using the H.
      bulbosum system. Linkage disequilibrium was detected for important agronomic
      characters and the effect of this disequilibrium on the choice of generation for
      doubled haploid production is discussed. 

PMID- 24276637
TI  - Analysis of the lymphatic stream to predict sentinel nodes in gastric cancer
      patients.
AB  - PURPOSE: To investigate the pattern of lymphatic drainage in gastric cancer
      patients to predict sentinel node placement according to tumor location. METHODS:
      A total of 462 pT1 or T2 gastric adenocarcinoma patients with metastasis to 1-3
      lymph nodes (LNs) who had undergone lymphadenectomy greater than D1+beta were
      included in the study. The distribution of metastatic LNs was evaluated according
      to tumor longitudinal and circumferential location. The incidence rate of
      atypical metastasis (skip or transversal metastasis) and related
      clinicopathologic factors were analyzed. RESULTS: The rates of skip and
      transversal metastasis were 15.8 % (73 of 462) and 10.3 % (23 of 224),
      respectively. Atypical metastasis was observed regardless of tumor location.
      Tumors that showed the most frequent atypical metastasis were located in the
      lower third and lesser curvature (LC) of the stomach (29.0 % for skip metastasis
      and 18.0 % for transversal metastasis). In uni- and multivariate analyses, an LC
      tumor was a risk factor for skip metastasis, and tumor located circumferentially
      in the LC or longitudinally in the lower third of the stomach was an independent
      risk factor for transversal metastasis. There was no correlation between tumor
      aggressiveness and atypical metastasis. CONCLUSIONS: Tumors at any location had a
      chance of atypical metastasis; however, those located longitudinally in the lower
      or circumferentially at the LC had a significantly higher chance of atypical
      metastasis compared to other locations. When sentinel node navigation surgery is
      applied, special care should be taken with tumors at these locations to prevent
      false-negative results.

PMID- 24276638
TI  - Neoadjuvant chemoradiation and duration of chemotherapy before surgical resection
      for pancreatic cancer: does time interval between radiotherapy and surgery
      matter?
AB  - BACKGROUND: Neoadjuvant chemoradiation and chemotherapy provided for borderline
      or locally advanced, potentially resectable pancreatic adenocarcinoma improves
      resectability rates. Response to therapy is also an important prognostic factor.
      There are no data in the literature regarding optimal time interval or duration
      of chemotherapy after chemoradiation before surgery, and pathologic response
      rates. Using our database, we evaluated these relationships and the effect on
      overall and progression-free survival. METHODS: We retrospectively analyzed the
      records of 83 patients who underwent neoadjuvant chemoradiation for locally
      advanced, potentially resectable, and borderline resectable pancreatic cancers
      before definitive resection. We divided patients into three groups according to
      time interval between completion of chemoradiation and resection: group A (0-10
      weeks), group B (11-20 weeks), and group C (>20 weeks). After chemoradiation,
      patients underwent ongoing chemotherapy before resection. Pathologic response was
      defined as major (>95% fibrosis), partial (50-94% fibrosis), or minor (<50%
      fibrosis). RESULTS: There were 56 patients in group A, 17 patients in group B,
      and 10 patients in group C. Patients in groups B and C were significantly more
      likely to experience a major response than group A (p < 0.013). Patients in group
      C had significantly increased median progression-free and overall survival (p <
      0.05). Multivariable classification and regression tree analysis demonstrated
      pathologic response to be the only significant factor in overall survival.
      CONCLUSIONS: Patients who underwent a prolonged time interval after neoadjuvant
      chemoradiation with ongoing chemotherapy were more likely to have an improved
      pathologic response at time of surgical resection, which was associated with
      improved median overall survival.

PMID- 24276639
TI  - A cost-utility analysis for prophylactic central neck dissection in clinically
      nodal-negative papillary thyroid carcinoma.
AB  - BACKGROUND: Although prophylactic central neck dissection (pCND) may reduce
      future locoregional recurrence after total thyroidectomy (TT) for low-risk
      papillary thyroid carcinoma (PTC), it is associated with a higher initial
      morbidity. We aimed to compare the long-term cost-effectiveness between TT with
      pCND (TT+pCND) and TT alone in the institution's perspective. METHODS: Our case
      definition was a hypothetical cohort of 100,000 nonpregnant female patients aged
      50 years with a 1.5-cm cN0 PTC within one lobe. A Markov decision tree model was
      constructed to compare the estimated cost-effectiveness between TT+pCND and TT
      alone after a 20-year period. Outcome probabilities, utilities, and costs were
      estimated from the literature. The threshold for cost-effectiveness was set at
      US$50,000 per quality-adjusted life year (QALY). Sensitivity and threshold
      analyses were used to examine model uncertainty. RESULTS: Each patient who
      underwent TT+pCND instead of TT alone cost an extra US$34.52 but gained an
      additional 0.323 QALY. In fact, in the sensitivity analysis, TT+pCND became cost
      effective 9 years after the initial operation. In the threshold analysis, none of
      the scenarios that could change this conclusion appeared clinically possible or
      likely. However, TT+pCND became cost-saving (i.e., less costly and more cost
      effective) at 20 years if associated permanent vocal cord palsy was kept <= 1.37
      %, permanent hypoparathyroidism was <= 1.20 %, and/or postoperative radioiodine
      ablation use was <= 73.64 %. CONCLUSIONS: In the institution's perspective,
      routine pCND for low-risk PTC began to become cost-effective 9 years after
      initial surgery and became cost-saving at 20 years if postoperative radioiodine
      use and/or permanent surgical complications were kept to a minimum.

PMID- 24276640
TI  - Tumor-associated macrophages promote oral cancer progression through activation
      of the Axl signaling pathway.
AB  - BACKGROUND: Recent studies suggest that tumor-associated macrophages (TAMs)
      promote tumor growth and metastasis. Our previous report demonstrated that Axl
      signaling promotes carcinogenesis and progression of oral squamous cell carcinoma
      (OSCC). This study aims to test the potential involvement of growth arrest
      specific gene 6 (Gas6)/Axl signaling in the protumoral effect of TAMs. METHODS:
      Co-culture experiments by incubation of OSCC cells (YD38 and OE) and macrophages
      (THP-1) were performed. The expression of Gas6/Axl and epithelial-mesenchymal
      transition (EMT) genes were examined in YD38 and OE cells. The effect of Gas6/Axl
      signaling on co-cultured cancer cells was further investigated by knocking down
      Axl expression and neutralizing Gas6. Axl and TAM distribution were analyzed by
      immunohistochemistry in OSCC tissues. RESULTS: Activation of Axl signaling and
      increased expression of mesenchymal markers, along with increased
      invasion/migration ability of OSCC cells, was noted upon co-culture with THP-1.
      Neutralization of Gas6 in the co-culture system or knockdown of Axl in YD38
      caused the co-culture effects to be diminished. Co-culture with THP-1 increased
      nuclear factor (NF)-kappaB nuclear translocation and transcription activity in
      YD38 cells. A significant association between the TAM count and expression of
      phosphorylated Axl (P = 0.004) was found in vivo cancer tissues. CONCLUSIONS:
      TAMs play a protumor role in OSCC and likely promote tumor progression through
      activation of the Gas6/Axl-NF-kappaB signaling pathway. Therefore, Gas6/Axl and
      NF-kappaB signaling in OSCC cells may be a putative target for therapeutic
      intervention.

PMID- 24276641
TI  - Anatomic extent of metastatic lymph nodes: still important for gastric cancer
      prognosis.
AB  - BACKGROUND: Currently, gastric cancer staging systems do not consider the
      anatomic extent of metastatic lymph nodes (mLNs) as a prognostic factor. We
      therefore investigated the prognostic impact of the anatomic extent of mLNs on
      gastric cancer. METHODS: The prognoses of 4,043 gastric cancer patients who
      underwent curative resection were analyzed. Patients with mLNs in lymph node (LN)
      stations 1-6 (n = 1,980) comprised the perigastric LN-positive (PLN) group, and
      patients with mLNs in LN stations 7-12 and 14 (n = 2,063) were assigned to the
      extraperigastric LN-positive (ELN) group. Overall survival was estimated using
      the Kaplan-Meier method, and hazard ratios (HRs) were calculated by the Cox
      proportional hazard model. RESULTS: The ELN group exhibited worse survival than
      the PLN group (p < 0.001), although there were differences in their
      clinicopathological features. When patients were stratified according to tumor
      node-metastasis stage, the ELN groups had unfavorable prognoses compared with the
      PLN groups (p < 0.05). There were significant differences in long-term survival
      when the nodal stage of the current staging systems were subdivided according to
      anatomic nodal extent (p < 0.05), although there was a strong association between
      the probability of having extraperigastric mLNs and N classification. In
      multivariate analysis using age, gender, tumor size, tumor location, histology, T
      classification, and the extent of mLNs as covariates, presence of
      extraperigastric mLNs was an independent prognostic factor (HR 1.89, 95 % CI 1.73
      2.07), along with age, tumor size, tumor location, and T classification.
      CONCLUSIONS: The anatomic extent of mLNs significantly affects patient prognosis.
      Including the anatomic extent of mLNs in the current staging system may predict
      gastric cancer prognosis more accurately in patients with the same stage of
      cancer.

PMID- 24276642
TI  - Melphalan: a promising agent in patients undergoing cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) has become an option for peritoneal carcinomatosis (PC).
      Frequently, these patients have failed systemic chemotherapies and surgeries,
      including CRS/HIPEC with traditional regimens (mitomycin-C or platinum based). An
      alternative agent for failed or repeated CRS/HIPEC is unknown. We hypothesize
      that melphalan is an alternative agent in patients with PC from aggressive
      primaries, including recurrences following failed regional therapies. METHODS: A
      retrospective review of a prospective database of 247 patients revealed 25
      patients (9 male and 16 female) who received intraperitoneal melphalan (50
      mg/m(2)) in 31 CRS/HIPEC procedures, of which 19 were repeated. Primary
      malignancies included 17 appendiceal, one colorectal, two ovarian, two uterine
      sarcomas, two primary peritoneal and one mesentery sarcoma. RESULTS: PC index
      (PCI) was >=20 in 76 % of patients (19/25). 88 % of patients (22/25) had complete
      cytoreduction. Seventeen patients were alive, with mean survival of 63.6 months,
      and eight patients are deceased. Overall survival (OS) for the entire group since
      diagnosis was 95.8, 84.5, 50.9, and 38.2 % at 1, 3, 5, and 10 years,
      respectively; OS since melphalan HIPEC was 89.4, 45, and 30 % at 1, 3, and 5
      years, respectively; and OS in patients with appendiceal malignancies was 91.7,
      48.1 and 32.1 % at 1, 3 and 5 years, respectively. There was no postoperative
      mortality. Grade III-IV morbidity was 23 % (7/31). Nine patents had neutropenia,
      controlled with filgrastim. CONCLUSIONS: Melphalan is an efficacious alternative
      agent in patients undergoing CRS/HIPEC for aggressive and recurrent peritoneal
      surface malignancies. Its postoperative significant myelosuppression effect
      should be addressed.

PMID- 24276643
TI  - Schistosoma japonicum tegumental protein 20.8, role in reproduction through its
      calcium binding ability.
AB  - Schistosomiasis threatens thousands of millions of peoples' health every year in
      the world. Schistosoma japonicum, a pathogen of schistosomiasis, is covered by a
      lipid bilayer membrane which plays an important role in nutrient transport,
      signal transduction, interaction with host's immune system, etc. Thus, molecules
      in the tegumental membrane have gained more and more interest for understanding
      biological and pathological processes of schistosoma. In this study, we found a
      protein from S. japonicum cDNA library which has a 20.8 KDa molecular weight
      (SjTP20.8). Recombinant SjTP20.8 was produced and purified from Escherichia coli.
      The recombinant protein could be detected by S. japonicum-infected mice and human
      sera, and it had been found localizing in the tegumental membrane of S. japonicum
      in the section using immunofluorescence assay. In electrophoretic mobility shift
      assay, the protein could bind calcium iron in neutral condition. Result of
      cercariae challenge experiment indicates antibody against this protein can
      protect mice from chronic hepatic fibrosis. Our results indicate the S. japonicum
      tegumental protein 20.8 is crucial for the parasite's calcium absorbing and
      reproduction. 

PMID- 24276644
TI  - Bioactivities of some essential oils against the camel nasal botfly, Cephalopina
      titillator.
AB  - Nasopharyngeal myiasis of camels is caused by the larvae of Cephalopina
      titillator. We determined the efficacy of essential oils (EOs) of pumpkin,
      Cucurbita maxima; lupinus, Lupinus luteus; garlic oil, Allium sativum; and
      peppermint, Mentha piperita, against the third larval stage of C. titillator
      using larval immersion tests. The positive control group was treated with
      ivermectin and the negative control one was treated with distilled water and few
      drops of Tween 80. Larvae were reared until adult emergence. The data indicated
      that complete larval mortalities were reached 24 h post treatment (PT) with 2 %
      pumpkin, 7.5 % garlic and peppermint, 30 % lupinus, and 0.15 % ivermectin. The
      lethal values, LC50s, were 0.20, 0.44, 0.42, 0.47, and 0.03 %, respectively.
      Pumpkin and ivermectin were 2 and 17 times, respectively, more effective than the
      other EOs. Ivermectin was seven times more intoxicating than pumpkin oil.
      Formation of pupae had been stopped after treatment of larvae with 2 % pumpkin,
      7.5 % garlic and peppermint, 30 % lupines, and 0.04 % ivermectin. Adult emergence
      had been completely ceased following treatment of larvae with 0.5 % EOs and 0.04
      % ivermectin. Morphological abnormalities were pronounced after treatments, and
      peppermint oil was the foremost cause of deformation in larvae (44 % PT with 7.5
      %) and pupae (40 % PT with 2 %). Pumpkin oil (6 %) was selected to be the drug of
      choice for controlling C. titillator. Besides their insecticidal effects, EOs are
      much safer than ivermectin regarding health and environmental issues.
      Consequently, EOs described herein merit further study as potential nasal drench
      for C. titillator control.

PMID- 24276646
TI  - Onset of parenting and stressful events.
AB  - The purpose of this study was to develop a list of stressful events associated
      with onset of parenting, and to rank the events and establish weights in a way
      that reflects the degree of disruption that would be caused should that event
      occur. Whether the rankings and weightings differ as a function of parent sex and
      maternal work status was also considered. The procedures for developing the list
      and the rankings and weightings are presented. Results indicate high internal
      consistency in weightings (.81 to .92) and significant differences in ranking
      between the four groups of parents (nonworking mothers, working mothers, fathers
      with nonworking wives, fathers with working wives) on two of the 21 events.
      Implications for parent education programs and research are discussed. 

PMID- 24276645
TI  - Stem cell therapy for the treatment of parasitic infections: is it far away?
AB  - Stem cell therapy is an interventional treatment that introduces new cells into
      damaged tissues, which help in treating many diseases and injuries. It has been
      proved that stem cell therapy is effective for the treatment of cancers, diabetes
      mellitus, Parkinson's disease, Huntington's disease, cardiovascular diseases,
      neurological disorders, and many other diseases. Recently, stem cell therapy has
      been introduced to treat parasitic infections. The culture supernatant of
      mesenchymal stem cells (MSCs) is found to inhibit activation and proliferation of
      macrophages induced by the soluble egg antigen of Schistosoma japonicum, and MSC
      treatment relieves S. japonicum-induced liver injury and fibrosis in mouse
      models. In addition, transplantation of MSCs into naive mice is able to confer
      host resistance against malaria, and MSCs are reported to play an important role
      in host protective immune responses against malaria by modulating regulatory T
      cells. In mouse models of Chagas disease, bone marrow mononuclear cell has been
      shown effective in reducing inflammation and fibrosis in mice infected with
      Trypanosoma cruzi, and transplantation of the bone marrow mononuclear cells
      prevents and reverses the right ventricular dilatation induced by T. cruzi
      infection in mice. Preliminary clinical trials demonstrate that transplantation
      of bone marrow derived-cells may become an important therapeutic modality in the
      management of end-stage heart diseases associated with Chagas disease. Based on
      these exciting results, it is considered by stating that it is firmly believed
      that, within the next few years, we will be able to find the best animal models
      and the appropriate stem cell type, stem cell number, injection route, and
      disease state that will result in possible benefits for the patients with
      parasitic infections, and stem cell therapy, although at an initial stage
      currently, will become a real therapeutic option for parasitic diseases. 

PMID- 24276647
TI  - Community support for adolescent parents and their children: The parent-to-parent
      program in Vermont.
AB  - Most adolescent parents now receive good prenatal and neonatal medical care, some
      receive limited amounts of parenting instruction, and increasing numbers can
      participate in school completion programs. But few programs address the social
      isolation and broad developmental disruptions that often accompany adolescent
      parenthood. This article describes the implementation and short-term effects of
      one program that does strive to meet adolescents' long-term, broad support needs.
      The Parent-to-Parent program is a home-based program designed to enhance the
      ability of adolescent parents to meet their young children's and their own
      developmental needs. Through long-term home visiting by specially trained local
      volunteers, parent group meetings, and work with local human service
      institutions, the program strives to (1) enhance the quality of parent-child
      interaction; (2) enhance the parents' ability to locate and acquire services that
      will help them meet basic needs; (3) enhance parent and child involvement in
      community life; and (4) help the parents become more aware of their own options
      for the future, and more capable of implementing the plans they make. 

PMID- 24276648
TI  - Young children in alcoholic families: A mental health needs-Assessment and an
      intervention/prevention strategy.
AB  - This study of children at risk for the development of mental health and/or
      chemical dependency problems utilized the Personality Inventory for Children
      (PIC) (Wirt, Seat & Broen, 1977) on 50 children of alcoholic families currently
      involved in treatment for alcoholism. Significant differences were discovered,
      with the subject children being deviant from normal on several of the clinical
      scales of the PIC. An innovative intervention/prevention strategy employing
      cognitive behavior modification principles was successfully used to teach a
      similar group of 18 children to understand and overcome upsetting feelings.
      Implications of the use of the PIC and the intervention/prevention strategy are
      explored. 

PMID- 24276650
TI  - FIT: Don't leave home without it.

PMID- 24276649
TI  - Peer counseling: Drug and alcohol abuse prevention.
AB  - A peer counseling program was developed as a method for preventing drug and
      alcohol abuse among high school juniors and seniors. The program was implemented
      and the results were monitored to evaluate the impact of the program on the
      students. An analysis of the data showed that the students were able to learn and
      utilize peer counseling skills but that the prevention of drug abuse could not be
      documented in this study. Subjective reports, however, were found to support the
      effects of the program. 

PMID- 24276651
TI  - Primary prevention program clearinghouse psychology Department-Dewey Hall
      University of Vermont, Burlington, VT. 05405.

PMID- 24276653
TI  - Old and new anti-epileptic drugs in pregnancy.
AB  - During the recent years, a significant number of anti-epileptic drugs have been
      approved for prescription in different countries. In addition, some other
      promising drugs are in various stages of development. Soon after each drug has
      found its place in the therapeutic arsenal, pregnancies with exposure occur, with
      an increased risk of birth defect and developmental disturbances. As regards the
      possible teratogenic effect of the new anti-epileptic drugs, apart some
      individual reports we have only the results of pre-clinical toxicological studies
      which are difficult to extrapolate to the human situation, because of the well
      known interspecies differences in pharmacokinetics and pharmacodynamics.
      Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically
      while these new drugs are prescribed as add-on medication. So, metabolic
      interactions between individual components of such drug combinations may induce
      unexpected teratogenic effects. Also as for the teratogenic effects of the 'old'
      drugs many questions have still to be defined. The most common and more important
      are which anti-epileptic drugs or combination of drugs is most safe for a
      particular woman with epilepsy and if there is an association between single anti
      epileptic drugs and specific malformations. The reason is that none of the
      available reports to date have studied a sufficient number of women with epilepsy
      exposed to anti-epileptic drug monotherapy during pregnancy. Other questions
      concern dose-effect relationships, a universally accepted definition of major and
      minor malformations, and the lack of a thorough, exhaustive evaluation of the
      other risk factors, apart from the drugs. All these questions need to be
      ascertained for both the old and the new anti-epileptic drugs. Owing to these
      considerations, in 1998 an European Register of anti-epileptic drugs and
      pregnancy was instituted. The primary objective of the study is to evaluate and
      determine the degree of safety, with respect to the human foetus, of anti
      epileptic drugs with reference to both old and new, and to individual drugs and
      drugs in combination. Secondary objectives are to establish the pattern of
      abnormalities, if any, associated with anti-epileptic drugs individually and in
      combination, to delineate drug-specific syndromes, if any, to evaluate dose
      effect relationships. Tertiary objectives are to provide references data for use
      in pre-pregnancy counselling, and for development of guidelines. The evaluation
      of other etiological risk factors is also considered. 

PMID- 24276652
TI  - Pseudolaric acid B induces caspase-dependent cell death in human ovarian cancer
      cells.
AB  - Pseudolaric acid B (PAB) is a diterpene acid isolated from the root and trunk
      bark of Pseudolarix kaempferi Gordon (Pinaceae). Recent studies have reported
      that PAB exhibits cytotoxic effects in several cancer cell lines. In the present
      study, we assessed its antitumor activity and molecular mechanisms in HO-8910 and
      A2780 ovarian cancer cells in vitro. We found that PAB reduced cell viability and
      induced apoptosis in a dose- and time-dependent manner in HO-8910 and A2780 human
      ovarian cancer cells. The induction of apoptosis was also accompanied by the
      regulation of Bcl-2 and XIAP family proteins, cytochrome c and Apaf-1. Moreover,
      we observed that PAB treatment resulted in the activation of caspase-3 and -9,
      which may partly explain the anticancer activity of PAB. Collectively, the
      present study for the first time suggests that PAB enhances apoptosis of HO-8910
      and A2780 cells through regulation of Bcl-2 and IAP family proteins. Moreover,
      the triggering of caspase-3 and -9 activation mediated apoptotic induction. Our
      results suggest that PAB may be a new therapeutic option for the treatment of
      ovarian cancers.

PMID- 24276654
TI  - Guidelines for the prevention of migraine.
AB  - Treatment of migraine has traditionally been divided into managing acute attacks
      and prophylactic treatment. Treatment of acute migraine has been the subject of
      many research papers and review articles in recent literature partly at the cost
      of prophylactic treatment, which is the focus of this review. The objective of
      prophylactic therapy is to reduce frequency, duration and severity of attacks in
      addition to optimize the patient's ability to function normally. Preventive
      therapy is usually undertaken in patients who have more than two migraine
      episodes per month or when less frequent have severely disabling headaches
      resistant to usual treatment. Beta-blocking drugs without intrinsic
      sympathomimetic activity (e.g. propranolol) are usually the first drugs of choice
      followed by tricyclic antidepressant agents (e.g. amitriptyline), non-steroidal
      anti-inflammatory drugs (e.g. naproxen), calcium antagonists (e.g. flunarizine)
      or valproate. The use of serotonin antagonists (e.g. methysergide) is limited
      because of their potential serious side effects. Migraine refractory to standard
      prophylactic therapy is very often the result of overuse of abortive antimigraine
      drugs. The choice of medication clearly depends on the patient's profile (age, co
      morbid medical conditions) and the contraindication and side effect profile of
      the drug. 

PMID- 24276655
TI  - Non-convulsive status epilepticus in children. A report of 12 cases.
AB  - OBJECTIVE: To look for pattern of non-convulsive status epilepticus in children
      with epilepsy at the Sultan Qaboos University Hospital, Sultanate of Oman.
      METHODS: Twelve children (6 male and 6 female) with non-convulsive status
      epilepticus were seen at Sultan Qaboos University Hospital from December 1992
      until December 1997. The diagnosis was suspected in children with previous
      history of seizures who had recent change in behavior, memory, automatism or
      ataxia, or children presenting with unexplained ataxia, speech loss and prolonged
      inattention for the first time. All the patients were observed in the hospital.
      Electroencephalogram correlation with the above clinical presentation, of at
      least 30 mintues was used to confirm the diagnosis. RESULTS: Complex partial
      seizures status and Lennox-Gastaut syndrome status constituted the majority (7
      cases). Intravenous midazolam and phenytoin sodium were used to control status in
      9 cases. On follow-up, 5 were adequately controlled, while 6 had recurrence. One
      patient was lost to follow-up. CONCLUSION: Non-convulsive status epilepticus
      should be suspected in children with recent onset change in speech, memory,
      school performance, unexplained ataxia and particularly in children with epilepsy
      who undergo an otherwise inexplicable change in behavior.

PMID- 24276656
TI  - Attitudes of Omani physicians to people with epilepsy.
AB  - OBJECTIVE: This study reports the results of a questionnaire design to elicit
      doctors views about epilepsy. METHODS: Sixty-two percent of medical staff working
      in different regions of Oman responded. The questionnaire covered certain topics
      regarding the source of the knowledge of the doctors on seizure disorders and the
      personalities and behavior of people with epilepsy. RESULTS: The study suggests
      that although doctors in Oman gained knowledge on epilepsy prior to medical
      education, more doctors judged people with epilepsy 'negatively' compared to
      'positively' for normal people. CONCLUSION: A developing country such as Oman
      needs to inculcate perceptions and attitude that are more realistic amongst their
      doctors toward people with epilepsy.

PMID- 24276657
TI  - Electrocorticography in the management of surgically treated epileptic patients.
AB  - OBJECTIVE: To report our experience on 8 patients with mean age of onset of
      seizures of 8 years, who had intra-operative electrocorticography monitoring
      during the surgical treatment of their medically intractable partial epilepsy.
      METHODS: Post-resection electrocorticography grades were according to Jay et al
      and seizure outcome was a according to Kobayashi et al grades. RESULTS: Five
      patients had temporal lobe surgery and 3 patients had extra temporal surgery.
      Four patients had post-resection electrocorticography grade A (no residual
      epileptic activity), two of them had seizure outcome grade 1 (free of seizures)
      and the other 2 had grade 11 (free of seizures on medication). The other 4
      patients had post-resection electrocorticography grade B (minimal residual
      epileptic activity) and all had seizure outcome grade 11 except one patient who
      had grade 111 (more than 50% reduction in seizure frequency). CONCLUSION: Despite
      the small size of our study, our results suggest that intra-operative
      electrocorticography may be an important tool in the surgical management of
      medically intractable epilepsy.

PMID- 24276658
TI  - Epilepsy and driving in Saudi Arabia. A pilot study.
AB  - OBJECTIVE: There is paucity of information on the driving pattern of epileptic
      patients in Saudi Arabia. The purpose of this study was to document the frequency
      of epileptic patients that drive and the factors associated with this. METHODS: A
      Hospital-based study with structured interviews of consecutively recruited
      patients who gave prior consent. Seizure types, extent of control and factors
      presumed to be associated with driving were documented. RESULTS: One hundred and
      thirty eight male epileptics (mean age: 32.7 years) were studied. Only 15
      patients (11%) were not driving. There was no difference in the mean ages of
      those who drove and those who did not (t = 0.69, p = 0.49); but the former group
      had a significantly higher proportion of subjects with uncontrolled seizures (z =
      2.52, p<0.01). Overall, 108 subjects (78%) were educated about the risks
      associated with driving. The major reason for driving was seizure control with no
      fear of accidents. The other reasons were: lack of money to employ drivers and
      non availability of other people to drive. On multivariate analysis, seizure
      control and negative history of attack while driving were the factors
      significantly associated with driving. CONCLUSION: The study showed a very high
      frequency of epileptic drivers whose decision to drive appeared to be associated
      with good seizure control and lack of attacks while driving. Health education
      about the risk of driving should continue especially for patients with
      uncontrolled attacks and generalized seizures.

PMID- 24276659
TI  - Profile of stroke in Bahrain.
AB  - OBJECTIVE: As no report on the pattern of stroke in Bahrain is available, we
      sought to determine the stroke types, the annual incidence rate, and the risk
      factors associated with different types of stroke in Bahrain nationals and
      expatriates in Bahrain. METHODS: Case records of patients admitted with stroke
      from January 1995 to December 1995 in a tertiary level hospital, the only one
      with a well established neurology service in Bahrain were reviewed. Diagnosis of
      stroke and its type were confirmed by clinical and computerized tomography of
      brain. Risk factor analysis was made based on clinical, laboratory and other
      relevant investigational data. RESULTS: The majority of strokes occurred in
      middle and late age Bahrainis. Males predominated in all types of strokes, except
      in the hemorrhagic type, among the Bahrainis. The crude annual incidence rate was
      57 per 100,000 Bahrainis. The frequency of stroke types in Bahrainis was cerebral
      infarction in 53%, cerebral hemorrhage in 30% and unspecified in 16.5%; as
      against 76%, 10% and 15% in non Bahrainis. Subarachnoid hemorrhage was rare (2%).
      Hypertension, dyslipidemia, diabetes mellitus and ischemic heart disease and
      smoking were common risk factors for ischemic and hemorrhagic strokes.
      CONCLUSION: Stroke incidence in Bahraini nationals is similar to that in
      developing countries and from other parts of the Arabian Peninsula. The
      differences observed in age and gender distribution and in the stroke types
      between Bahraini nationals and non Bahraini expatriates is most likely a
      reflection of the demographic structure existing in Bahrain.

PMID- 24276660
TI  - X-linked adrenoleukodystrophy. The Saudi experience.
AB  - OBJECTIVE: To evaluate the clinical, biochemical, neuroradiological, and
      neurophysiological findings of patients with X-linked adrenoleukodystrophy.
      METHODS: Retrospective study evaluating the data of 10 X-linked
      adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and
      Research Centre, Riyadh, Saudi Arabia. RESULTS: The common presenting symptoms
      were deterioration in school performance, vision and hearing, behavioral changes,
      and seizures. Eight patients survived 1-4 years and one patient 12 years after
      the initial presentation, while one patient expired. Six patients had the
      childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy
      form. Six are in an advanced stage of the disease and 3 have mild to moderate
      spasticity. All except 2 manifested moderate to severe dementia with variable
      degrees of visual loss. Decreased hearing and features of adrenal insufficiency
      were seen in 7 patients. Very long chain fatty acids were significantly increased
      in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was
      increased in all. The characteristic high-signal intensity of parieto-occipital
      white matter on brain magnetic resonance imaging T2-weighted images was observed
      in all patients. Two patients had functional study of the brain, which showed
      hypometabolic activity in gray and white matter of the occipital lobes. Various
      neurophysiological abnormalities were detected. The response to different
      treatment modalities was not promising. CONCLUSION: The disease is more common
      than had been previously recognized due to phenotypic variability and a wide
      spectrum of presentations. This report describes various aspects of this disorder
      and emphasizes the importance of early identification and treatment of
      asymptomatic but biochemically affected individuals, since all current
      therapeutic approaches are disappointing if overt neurological abnormalities have
      been already developed.

PMID- 24276661
TI  - Parkinson's disease. Clinical and electrophysiology evaluation.
AB  - OBJECTIVE: Identification of the clinical spectrum and the electrophysiological
      responses of a Saudi population with Parkinson's disease as opposed to a matched
      normal population. METHODS: Fifty four subjects (41 males and 13 females) were
      selected for the study. The patients were clinically evaluated for the occurrence
      of Parkinson's disease symptoms, as well as other associated medical conditions.
      All patients had brain computerized tomography scans. Electrophysiological tests
      were performed on all patients using the Medelec ST 10 Sensor 59394 Model. These
      tests included somatosensory evoked response of median nerves, brain stem
      auditory evoked responses and visual evoked responses. The significant
      differences in these evoked responses between the patients with Parkinson's
      disease and normal patients were statistically evaluated. RESULTS: Twenty six out
      of the 40 computerized tomography brain scans which had been carried out showed
      normal brain morphology and 5 had a clear evidence of cerebrovascular disease
      while only 9 showed distinctive brain atrophy. The mean values for the brain stem
      auditory evoked response, the somatosensory evoked response and the visual evoked
      responses were higher in patients with Parkinson's disease as compared to those
      who did not have the disease. Significant differences were only seen as prolonged
      latencies in median nerve somatosensory evoked response, as well as delayed waves
      I and V on the brain stem auditory evoked response. Inter-wave latencies,
      however, were not significantly different. CONCLUSION: Parkinson's disease in a
      Saudi population showed significant differences to somatosensory evoked response
      and brain stem auditory evoked response electrophysiological data as compared to
      age-matched controls, however, the clinical characteristics of Parkinson's
      disease in Saudi patients are not significantly different from those reported for
      patients elsewhere.

PMID- 24276662
TI  - Effect of hemodialysis on autonomic dysfunction in patients with chronic renal
      failure.
AB  - OBJECTIVE: The main objective of this study is to use the method of complex
      demodulation combined with posture entrainment protocol (changing from supine to
      standing position) to characterize the autonomic dysfunction before and after
      hemodialysis session in patients with chronic renal failure. METHODS: Twenty
      patients maintained on hemodialysis for an average 18 months were studied. All
      patients were dialysed regularly three times a week, each time for 4 hours.
      Electroencephalograms were measured for ureamic patients before and after
      hemodialysis. Heart rate variability signals derived from electroencephalograms
      were recorded during the supine and standing positions. Complex modulation method
      is employed to investigate the sympathetic and parasympathetic activity before
      and after hemodialysis. RESULTS: It is possible by using experimental posture
      entrainment protocol (supine and standing positions) combined with the method of
      complex demodulation to produce the average low and high frequency response of
      heart rate variability mediated by autonomic nervous system for twenty uraemic
      patients before and after hemodialysis sessions in both supine and standing
      position. The high amplitude of low and high frequency response of heart rate
      variability of twenty uraemic patients on standing and poststanding after
      hemodialysis sessions indicates the improvement of autonomic function compared
      with the same patients before hemodialysis sessions (p < 0.001). The decrease of
      level of chemical components in blood such as creatinine and urea after
      hemodialysis increases the modulation of stimulus (posture entrainment) and
      consequently the better function of autonomic nervous system. CONCLUSION: The
      analysis of heart rate variability signals for twenty uraemic patients before and
      after hemodialysis using complex demodulation combined with posture entrainment
      protocol seems promising in assessing the autonomic function in chronic renal
      failure patients. Further studies may be needed to develop quantitative indices
      for possible screening and early diagnosis of autonomic dysfunction in end stage
      renal failure using this methodology.

PMID- 24276663
TI  - Substance dependence. A hospital based survey.
AB  - OBJECTIVE: To collect basic data on multiple and diverse issues such as drugs of
      dependence, smoking, initiation age, injection related harm, nutritional status,
      trauma, accidents, abnormal laboratory parameters and co-morbid conditions.
      METHODS: Seven hundred and ninety nine subjects from a voluntary detoxification
      unit were studied. Four hundred and ninety seven charts from June 1995 to
      December 1995 were reviewed retrospectively. For the other 302 subjects admitted
      between September 1996 to December 1996, information regarding drug use, smoking,
      trauma, accidents and co-morbid conditions was recorded during the admission
      interview while the remaining data was later obtained from the charts. RESULTS:
      Sixty eight percent were under 35. Ninety seven percent were smokers and 55%
      started smoking before the age of 15. Sixty four percent initiated drugs before
      the age of 25 while 34% had been on drugs for less than 5 years. Eighty seven
      percent were using heroin or alcohol. Fourteen percent were dependent on more
      than one drug. Among heroin users 91% were injecting, 21% had injection related
      complications, 69% had Hepatitis C Virus and 0.40% died. Forty four percent had
      at least one current medical disorder, 59% had one abnormal labarotory parameter
      and 21% below normal Body Mass Index. Nine percent had mental disorders and 1%
      presented with overdose. Twenty nine percent reported unintentional injuries and
      12% reported of road traffic accidents. Seventeen point five percent had family
      history of drug use, 4.5% had mental disorders and 87% physical disorders.
      CONCLUSION: More accurate and reliable data is required. Current services need to
      be improved. Preventative measures should focus on early detection and
      intervention and a central body for information collection should be established.

PMID- 24276664
TI  - Hypernatremic metabolic myopathy due to hypothalamic dysfunction.
AB  - We report a patient with muscle weakness secondary to elevated serum sodium
      level. The cause of the elevated sodium level and the mechanism involved in
      producing muscle weakness are discussed. 

PMID- 24276665
TI  - Abdominal muscle paralysis in herpes zoster.
AB  - Herpes zoster or Shingles, an inflammatory viral disease caused by varicella has
      classical clinical presentation with herpetic morphological pattern exhibited
      along one or more dermatomes. The self limiting skin disease is accompanied by
      pain and burning sensations leading to post herpetic neuralgia. The sensory
      component of the disease is so prominent that the motor involvement is often
      overlooked. It was not known till recently that profound muscle weakness can be a
      part of this syndrome. We report 2 cases of herpes zoster who had prominent
      appreciable motor weakness of the abdominal muscles following the disease. The
      weakness however has a better prognosis and the lesions in both of our patients
      healed in 6 months without leaving any residual paralysis. 

PMID- 24276666
TI  - Chronic inflammatory demyelinating polyneuropathy with papillodema and response
      to immunoglobulins.
AB  - Chronic inflammatory demyelinating polyneuropathy is considered as a chronic form
      of Guillain-Barre syndrome differing from it in response to steroids, course and
      prognosis. Papillodema although rare is not an uncommon feature. Here we report a
      case of florid papillodema in a patient of chronic inflammatory demyelinating
      polyneuropathy, discuss the underlying mechanisms in relation to cerebrospinal
      fluid pressure and protein content and response to intravenous immunoglobulins. 

PMID- 24276667
TI  - An unusual association between oral sarcoma and bulbar palsy.
AB  - A 90 year old male presented with symptoms and signs of right lower cranial
      nerves palsy. A small mass was found on the right side at the back of his mouth.
      Light microscopy and histoimmunochemical studies of the biopsy of the mass showed
      an alveolar soft part sarcoma arising from the right myohyoid muscle. The unusual
      location and presentation of this rare tumor is discussed. 

PMID- 24276668
TI  - Visual loss after coronary artery bypass surgery.
AB  - Anterior ischemic optic neuropathy is caused by microvascular occlusion of the
      prelaminar or laminar portion of the optic nerve head. The main types are
      arteritic, non-arteritic, and autoimmune. Few cases were reported following
      coronary artery bypass surgery. A 63-year-old man, who is both diabetic and
      hypertensive, underwent coronary artery bypass graft complicated postoperatively
      by sudden visual loss in his right eye. The diagnosis was non-arteritic anterior
      ischemic optic neuropathy. Possible predisposing factors were crowded disc and
      internal carotid artery stenosis. 

PMID- 24276669
TI  - Radiology quiz.

PMID- 24276670
TI  - Effect of hyaluronic acid incorporation method on the stability and biological
      properties of polyurethane-hyaluronic acid biomaterials.
AB  - The high failure rate of small diameter vascular grafts continues to drive the
      development of new materials and modification strategies that address this
      clinical problem, with biomolecule incorporation typically achieved via surface
      based modification of various biomaterials. In this work, we examined whether the
      method of biomolecule incorporation (i.e., bulk versus surface modification) into
      a polyurethane (PU) polymer impacted biomaterial performance in the context of
      vascular applications. Specifically, hyaluronic acid (HA) was incorporated into a
      poly(ether urethane) via bulk copolymerization or covalent surface tethering, and
      the resulting PU-HA materials characterized with respect to both physical and
      biological properties. Modification of PU with HA by either surface or bulk
      methods yielded materials that, when tested under static conditions, possessed no
      significant differences in their ability to resist protein adsorption, platelet
      adhesion, and bacterial adhesion, while supporting endothelial cell culture.
      However, only bulk-modified PU-HA materials were able to fully retain these
      characteristics following material exposure to flow, demonstrating a superior
      ability to retain the incorporated HA and minimize enzymatic degradation, protein
      adsorption, platelet adhesion, and bacterial adhesion. Thus, despite bulk methods
      rarely being implemented in the context of biomolecule attachment, these results
      demonstrate improved performance of PU-HA upon bulk, rather than surface,
      incorporation of HA. Although explored only in the context of PU-HA, the findings
      revealed by these experiments have broader implications for the design and
      evaluation of vascular graft modification strategies. 

PMID- 24276671
TI  - Biodistribution of PAMAM dendrimer conjugated magnetic nanoparticles in mice.
AB  - Fluorescein-loaded magnetic nanoparticles (FMNPs) have been increasingly utilized
      in nanomedicine due to their unique properties. In this study, polyamidoamine
      (PAMAM) dendrimer was used to modify the FMNPs through bifunctional polyethylene
      glycol linker. The obtained PAMAM modified magnetic nanoparticles (PFMNPs) were
      characterized by transmission electron microscope, thermogravimetric analysis,
      zeta potential titration, and fourier transform infrared spectroscopy. The effect
      of PAMAM conjugation on the biodistribution of FMNPs and PFMNPs were investigated
      by confocal laser scanning microscopy and inductively coupled plasma atomic
      emission spectrometry, respectively. It was revealed that PAMAM conjugation
      resulted in a lower uptake of FMNPs in the lung and less aggregation in the
      liver, whereas a higher uptake in brain and testis. Furthermore, the serum
      biochemical and the hematological analysis indicated the PFMNPs caused no
      significant changes in enzymes reflective of inflammatory response or organ
      toxicity. 

PMID- 24276673
TI  - Assessing somatic symptoms in clinical practice.

PMID- 24276672
TI  - Elevated levels of exhaled nitric oxide in patients with anorexia nervosa.
AB  - BACKGROUND: Nitric oxide (NO) is involved in eating behavior and inflammatory
      response. Moreover, there is evidence that NO production is altered in patients
      with anorexia nervosa (AN). AIM: To assess whether the overproduction of NO in AN
      can affect NO level in exhaled air. MATERIALS AND METHODS: Exhaled NO level was
      studied in 23 girls with AN and compared with that of healthy age- and gender
      matched nonatopic controls. RESULTS: Exhaled NO levels were significantly higher
      in girls with AN compared with healthy age-matched controls. CONCLUSIONS: It
      appears that anorexia nervosa was accompanied by a higher level of exhaled NO,
      likely resulting from a systemic increase in NO production because of the severe
      catabolic state.

PMID- 24276674
TI  - Electronic media: what are we teaching our children?

PMID- 24276676
TI  - Usefulness of controlled aliasing in parallel imaging results in higher
      acceleration in gadoxetic acid-enhanced liver magnetic resonance imaging to
      clarify the hepatic arterial phase.
AB  - PURPOSE: We aimed to determine whether the controlled aliasing in parallel
      imaging results in higher acceleration (CAIPIRINHA) technique could improve the
      image quality of the hepatic arterial phase of gadoxetic acid-enhanced liver
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: A total of 320 patients
      underwent gadoxetic acid-enhanced liver MR imaging: a conventional protocol (a
      fixed scan delay and 2-mL/s injection) using a standard 3-T MR system (Trio-Tim;
      Siemens, commercialized since 2005) (group A), an optimized protocol (bolus
      tracking and 1-mL/s injection) using a standard 3-T MR (group B), an optimized
      protocol using a new 3-T MR (Skyra; Siemens, commercialized since 2012) (group
      C), and an optimized protocol with CAIPIRINHA using a new 3-T MR (group D). The
      image quality of the hepatic arterial phase was graded using a 4-point rating
      scale from 1 (no artifacts) to 4 points (non-diagnostic images with severe
      artifacts). The differences in image quality scores among the 4 groups were
      evaluated. In addition, the detection rates of hypervascular hepatocellular
      carcinomas among the 4 groups were evaluated. RESULTS: Scores of 4 points were
      observed in groups A (n = 7), B (n = 5), and C (n = 3) but not in group D. The
      median image quality score was 2 in groups A and B and 1 in groups C and D. From
      group A to group D, the median image quality score decreased significantly (P =
      0.0001). The median image quality score was significantly lower in group D than
      in groups A and B (P = 0.0001 and 0.001, respectively), whereas there was no
      significant difference observed between groups C and D (P = 0.656). The detection
      rates of hypervascular hepatocellular carcinomas on the hepatic arterial phase
      were not significantly different among the groups (all P > 0.03), except between
      groups A and D (P = 0.007). CONCLUSIONS: The CAIPIRINHA technique improved the
      image quality of hepatic arterial phase imaging with gadoxetic acid, reducing the
      number of non-diagnostic arterial phase studies.

PMID- 24276677
TI  - 3D ultrasonography is as accurate as low-dose CT in thyroid volumetry.
AB  - AIM: The purpose of this study was to compare thyroid volumetry by three
      dimensional mechanically swept ultrasonography (3DmsUS) and low-dose computed
      tomography (ldCT). PATIENTS, METHODS: 30 subjects referred for radioiodine
      therapy of benign thyroid diseases were subjected to 3DmsUS and ldCT. A
      prerequisite of 3DmsUS analyses was that the scans had to capture the entire
      thyroid, excluding therefore cases with a very large volume or retrosternal
      portions. The 3DmsUS data were transformed into a DICOM format, and volumetry
      calculations were performed via a multimodal workstation equipped with standard
      software for cross-sectional imaging. Volume was calculated applying both the
      ellipsoid model and a manually tracing method. Statistical analyses included 95%
      confidence intervals (CI) of the means and limits of agreement according to Bland
      and Altman, the latter including 95% of all expected values. RESULTS: Volumetric
      measurements by 3DmsUS and ldCT resulted in very high, significant correlation
      coefficients, r = 0.997 using the ellipsoid model and r = 0.993 with the manually
      tracing method. The mean relative differences of the two imaging modalities
      proved very small (-1.2+/-4.0% [95% CI -2.62; 0.28] using the ellipsoid model; 
      1.1+/-5.2% [95% CI -2.93; 0.80] using the manually tracing method) and the limits
      of agreement sufficiently narrow (-9.1% to 6.8%; -11.3% to 9.2%, respectively).
      CONCLUSION: For moderately enlarged thyroids, volumetry with 3DmsUS proved
      comparable to that of ldCT, irrespective of whether the ellipsoid model or the
      manually tracing method was applied. Thus, 3DmsUS qualifies as a potential
      alternative to ldCT, provided that the organ is completely accessible. The use of
      a standard workstation for cross-sectional imaging with routine software did not
      prove problematic.

PMID- 24276678
TI  - Li-rich thin film cathode prepared by pulsed laser deposition.
AB  - Li-rich layer-structured cathode thin films are prepared by pulsed laser
      deposition. X-ray diffraction (XRD), field emission scanning electron microscope
      (FESEM), X-ray photoelectron spectroscopy (XPS) and electrochemical testing in
      half battery cells are used to characterize crystal structure, surface
      morphology, chemical valence states and electrochemical performance of these thin
      films, respectively. It is observed that partial layer to spinel transformation
      takes place during post annealing, and the layered structure further gradually
      transforms to spinel during electrochemical cycling based on the analysis of
      dQ/dV. Electrochemical measurement shows that the thin film electrode deposited
      at 350 mTorr and post-annealed at 800  degrees C possesses the best performance.

PMID- 24276679
TI  - In response to "Lipomatosis of the sciatic nerve secondary to compression by a
      desmoid tumor".

PMID- 24276680
TI  - Atraumatic bilateral scapular spine fracture several months after bilateral
      reverse total shoulder arthroplasty.
AB  - We report an 89-year-old woman with bilateral atraumatic scapular spine fracture
      several months after bilateral reverse total shoulder arthroplasty (RTSA).
      Recently, RTSA has gained popularity in the surgical treatment of complex
      shoulder disorders such as cuff tear arthropathy. However, scapular fractures may
      occur several months after surgery as a late complication of this procedure. In
      this case report we focus on a relatively uncommon subtype, the scapular spine
      fracture. Although well-known in the orthopedic literature, radiologists are less
      familiar with this complication. To the best of our knowledge, bilateral scapular
      fractures have not yet been reported. 

PMID- 24276681
TI  - Selfcompatibility in microspore-derived doubled-haploid rye lines and single
      grain selection for alkylresorcinol content.
AB  - From a total of 138 green androgenetic rye lines, 25 were fertilized and examined
      in field tests: 7 were heterozygous and 18 were homozygous. Of the homozygotes, 4
      turned out to be selfincompatible, while 14 set seed after selfing. Four
      characters were analyzed in detail: 100 kernel weight, plant height, ear length,
      and alkylresorcinol content. Here we present the first approach in prescreening
      selfcompatible androgenetic doubled-haploid rye plants with the single grain
      procedure. The usefulness of this method was confirmed by quantitative resorcinol
      determination in the following generation. Furthermore, it was demonstrated that
      all the homologues of the alkylresorcinol were equally reduced. For all
      characters the means of the different anther derived lines exceeded the means of
      the controls in both directions, to the positive as well as to the negative side.
      The incorporation of such a haploid breeding step into breeding programs is
      discussed. 

PMID- 24276682
TI  - Trisomics of ryegrass and their transmission.
AB  - Primary trisomics of perennial ryegrass, Lolium perenne L., were studied for
      meiotic behaviour, fertility, morphology and trisome transmission. Trisomics
      differed from each other in mean meiotic association, pollen fertility, seed set
      and morphology. The combined cytomorphological data suggested that the
      investigated trisomic plants included trisomes 2 to 7. No pollen transmission of
      trisomes was detected. Female transmission of trisomes ranged from 12% for tri 3
      to 37% for tri 4 with a mean of 24% for the six trisomes. Trisome transmission
      was not related to either chromosome size or trivalent/univalent frequency,
      although the larger trisomes formed trivalents more frequently than the smaller
      trisomes. 

PMID- 24276683
TI  - The mutated locus and the changes in the background genotype of jute (C.
      olitorius L.).
AB  - Morphologically similar leaf characters of two X-ray induced and independently
      isolated jute mutants from a common mother cultivar, JRO-632, were controlled by
      the same locus. However, they differed significantly in such quantitative
      characters as plant height, middle diameter, days to flower, node number and
      fibre yield/plant. Combining ability analysis from a 9 X 9 diallel set of
      crossing including these two mutants revealed that the mutants significantly
      differed in general combining ability (gca) effects for most of the traits in
      either direction or magnitude. Specific combining ability (sca) effects of the
      inter-mutant cross, as well as crosses with the common mother cultivar, JRO-632,
      also differed for most of the traits studied. It was suggested that X-irradiation
      induced random mutations effecting changes in the common background genotype,
      independent of the mutated locus. 

PMID- 24276684
TI  - Analysis of the rye chromosome constitution and the amount of telomeric
      heterochromatin in the widely and narrowly adapted hexaploid triticales.
AB  - Investigations were made on the rye chromosome constitution and on the presence
      of telomeric heterochromatin in rye chromosomes of the 26 most widely and 24 most
      narrowly adapted triticale strains. Among widely adapted lines, 22 (85%) had a
      complete rye genome and four triticales only had chromosomal R-D genome
      substitutions. Twenty-three (96%) of the 24 most narrowly adapted triticales had
      substitutions between the chromosomes of the R and D genomes. The most widely
      adapted triticales accumulated fewer modified rye chromosomes in comparison to
      narrowly adapted lines. They had from one to three rye chromosomes with
      heterochromatic deletions: 46% of widely adapted lines had two modified rye
      chromosomes; 34% had three modified rye chromosomes, and 19% had a single
      modified rye chromosome. In widely adapted strains, the 1R, 4R, 5R and 6R
      modified chromosomes were observed; they were present in 80%, 73%, 50% and 11% of
      the cases, respectively. The most narrowly adapted triticales had from two to
      four modified rye chromosomes: 58% of the strains had three modified rye
      chromosomes; 29% had four modified rye chromosomes and 12% had two modified rye
      chromosomes. The modified 4R and 5R chromosomes were present in all of these
      lines. The 1R (modified), 6R (modified) and 7R (modified) were found in 83%, 25%
      and 16%, respectively, of the narrowly adapted strains.Results support the
      previous observations (Pilch 1980b) that a wide adaptation of hexaploid
      triticales is associated with the presence of the full potential of rye genome,
      and that it is independent of the amount of telomeric heterochromatin possessed
      by rye chromosomes. 

PMID- 24276685
TI  - Correction.

PMID- 24276686
TI  - Estimators of repeatability.
AB  - Analysis of variance and principal components methods have been suggested for
      estimating repeatability. In this study, six estimation procedures are compared:
      ANOVA, principal components based on the sample covariance matrix and also on the
      sample correlation matrix, a related multivariate method (structural analysis)
      based on the sample covariance matrix and also on the sample correlation matrix,
      and maximum likelihood estimation. A simulation study indicates that when the
      standard linear model assumptions are met, the estimators are quite similar
      except when the repeatability is small. Overall, maximum likelihood appears the
      preferred method. If the assumption of equal variance is relaxed, the methods
      based on the sample correlation matrix perform better although others are
      surprisingly robust. The structural analysis method (with sample correlation
      matrix) appears to be best. 

PMID- 24276687
TI  - An analysis of genes for resistance against two Indian cultures of stem rust
      races of two bread wheats.
AB  - Two bread wheat accessions, E5008 and E6160, have been genetically analysed for
      resistance genes effective against Indian cultures of stem rust races, 15C and
      122. The inheritance of resistance to each race has been determined from the F1
      and F2 of the crosses (resistant parents with the susceptible variety, 'Agra
      Local') and F2 progenies from the backcross to 'Agra Local'. Tests have been
      performed to see if the two varieties carry common genes/s for resistance. The
      identity of the genes for resistance has been established from relevant crosses
      with single gene lines carrying known genes for resistance.A single dominant gene
      effective to race 15C in E5008 has been demonstrated to be Sr9b. Of the two
      recessive genes, each producing distinct infection types (0; and 1-3) against
      race 122, one gene has been inferred to be Sr12 and the second to be a hitherto
      undesignated gene.The resistance of E6160 against race 15C is controlled by two
      genes, one dominant and one recessive. The dominant gene has been identified as
      Sr9b. The recessive gene has been inferred to be a new gene. Similarly, a
      dominant gene effective against race 122 in E6160 has been observed to be
      different from those so far designated. In addition, the presence of modifier
      gene/s in the variety, E6160 has been suggested. 

PMID- 24276688
TI  - Race-specific interactions between wheat genotypes and Indian cultures of stem
      rust.
AB  - Near isogenic/substitution lines of stem rust resistance genes in different
      backgrounds of 'Marquis', 'Chinese Spring' and W 2691 and certain varieties with
      known genes for stem rust resistance were tested against each of 19 Indian
      cultures of stem rust races/biotypes (14, 15, 17, 21, 21A-1, 24, 34, 40, 40A, 42,
      42B, 117, 117A, 117A-1, 122, 184, 194, 222 and 295). Sr 24 ('Sear's 3D/Ag'), Sr
      24 (TR 380-27 4/3 Ag 14-White seeded recombinant with 'Agent' type resistance),
      Sr 25 ('Sear's 7D/Ag'), Sr 26 ('Eagle'), Sr 26 (Knott's 6A/Ag translocation), Sr
      27 (WRT 238-5), Combination line (Sr Tt1 + Sr 9b) were observed to be completely
      effective against all the 19 cultures tested. In addition, a number of lines,
      such as TAF2d (Sr Agi), Line W(Sr Tt2) and Combination III (Sr Tt1 + Sr 9e), were
      found to be effective against at least three of the most prevalent races (21, 40A
      and 117A-1) and a virulent race 122 in Indian natural population. Lines carrying
      genes other than Sr 2, Sr 9a, Sr 9f ('Chinese Spring') and Sr 15 ('Norka'), and
      Line E were found to be resistant to one or more cultures of stem rust.The
      background effect upon the expression of a gene was observed by comparing the
      range of infection on single gene host lines in either different backgrounds
      and/or in cultivars with known genes for stem rust resistance against the 12
      cultures of stem rust races found in India. 

PMID- 24276689
TI  - Inheritance of heading date, plant height, ear length and spikelets per spike in
      an intervarietal cross of wheat.
AB  - A study to obtain information on early segregating generations of an
      intervarietal cross 'WG 357' X 'Tobari 66' in spring wheat on the genetics of
      days to heading, plant height, ear length and spikelets per spike was conducted.
      'WG 357' has amber, hard and lustrous grains and is a well adapted high yielding
      variety of North India whereas 'Tobari 66' is red grained introduction from
      CIMMYT.The parental F1, F2, B1, B2, biparentals, F3 (parents of biparentals), F3
      bulk and F4 bulk generations were studied in order to provide analysis of
      generations means (Mather 1949; Hayman 1958) and variance component analysis
      (Kearsay 1965; Perkins and Jinks 1970).There were highly significant differences
      among the generations for all the characters studied. There were significant
      differences among the F3 lines as well as among the biparental progenies. Only in
      case of ear length was the contrast between the two also significant. The mean
      value of most of the generations arising from the cross fell between the parental
      range.The three-parameter model failed to account for the variation in generation
      means in the case of days to heading. This character was concluded to be
      influenced by linkage and higher order interactions. For the other characters the
      three parameter model was adequate. For all characters, additive gene effects
      were most important as compared to dominance gene effects.The analysis of gene
      action as provided by the generation variance indicated that additive variance
      was much more pronounced as compared to dominance variance. The heritability was
      high for days to heading (71 per cent for narrow sense and 80 per cent in broad
      sense) and plant height (62 and 93 per cent in narrow and broad sense
      respectively.The implications of the results in breeding programmes have been
      discussed. 

PMID- 24276690
TI  - The effects of nuclear mutation on chloroplast development : Part 1: chloroplast
      DNA, proteins, ribosomes, hormones and tissue cultures.
AB  - Under greenhouse conditions the dark green wild type (su/su) tobacco grows 2-3
      times faster than the yellow mutant (Su/su) and contains five-fold more
      chlorophyll. On a fresh weight basis, however, both genotypes contain similar
      amounts of RuBPCase and fraction 11 protein in approximately equal proportion and
      have similar levels of 70s and 80s ribosomes. When seedlings are cultured on agar
      medium supplemented with sucrose and equal concentrations of IAA and kinetin or
      kinetin alone, a drastic reduction of RuBPCase and free 70s ribosomes, but not of
      chlorophyll content, were observed. Moreover, albino (Su/Su) seedlings developed
      on supplemented media still contain appreciable amounts of RuBPCase and free 70s
      ribosomes although chlorophyll levels are extremely low indicating no correlation
      between RuBPCase and chlorophyll content. RuBPCase crystallized from both wild
      type and yellow mutant plants seem to have identical composition and structure
      when examined by isoelectric focusing, amino acid analysis or peptide mapping
      techniques. The slow-growing yellow mutant is apparently deficient only in
      chlorophyll of the light harvesting chlorophyll-protein complex but with no
      alteration of the protein moiety or chlorophyll a/b ratio. 

PMID- 24276691
TI  - Chloroplast DNA assorts randomly in intraspecific somatic hybrids of Nicotiana
      debneyi.
AB  - Plants were regenerated following intraspecific fusion of leaf protoplasts from
      two naturally occurring genotypes of Nicotiana debneyi. The two genotypes
      differed in the EcoRl fragmentation pattern of chloroplast DNA and in the nuclear
      coded phosphoglucomutase (Pgm) isozymes. There was no conscious selection for
      hybrid genotypes during protoplast culture or plant regeneration. Among 225
      plants screened for Pgm, six were identified as nuclear hybrids. Restriction
      endonuclease and filter hybridisation analysis revealed that the cytoplasms of
      the hybrids contained one or other but never both parental chloroplast DNAs. The
      sorting out of chloroplasts was random and complete; the limit of detecting a
      rare chloroplast-DNA type in a mixture was 0.1%. 

PMID- 24276692
TI  - Evidence for a race-specific resistance factor in some lettuce (Lactuca sativa
      L.) cultivars previously considered to be universally susceptible to Bremia
      lactucae regel.
AB  - Previously undetected race-specific resistance to Bremia lactucae (downy mildew)
      was located in many lettuce cultivars hitherto considered to be universally
      susceptible to this disease. This resistance factor(s) may also be widely
      distributed in other cultivars known to carry combinations of already recognised
      factors R1 to R11. Specific virulence to match this resistance is almost
      invariably present in pathogen collections. This situation may be either a relic
      of the evolutionary history of the B. lactucae - L. sativa asssociation or may
      reflect a rare mutation in B. lactucae for avirulence on all but a few
      specialised L. sativa genotypes. 

PMID- 24276693
TI  - Genetic analysis of seed yield, oil content and their components in safflower
      (Carthamus tinctorius L.).
AB  - The genetic architecture of seed yield, oil content and their components was
      studied in a diallel cross of F1 and F2: eleven parents, representing an adequate
      diversity for all considered characters in safflower were used. Combining ability
      analysis revealed the predominance of gca variance for plant height, total
      capitula, seed weight, seed number and seed yield in F1 and F2 generations and
      for days to flowering and oil content in F1. The analysis of components of
      variance indicated that the non-additive factor was the major influence on total
      capitula and seed yield in F1s, and F2s, and on plant height, seed weight and
      seed number in the F2 alone. The heterogeneity of the dominance component over
      generations has been attributed to coupling phase linkage. All four Indian
      parents, namely S 144, A1, MS 49 and 6 spl, together with G 1157 and US 104 in
      the exotic group, were the best combiners for seed yield and/or for one of its
      components while the remainder of the exotic parents were characterized by high
      gca effects for oil content. VFstp 1 and Frio were the only parents approximating
      both properties of oil content and seed yield. Breeding methods, such as
      biparental mating followed by reciprocal recurrent selection, were suggested for
      the simultaneous improvement of seed yield and oil content. 

PMID- 24276694
TI  - Chip-on-foil devices for DNA analysis based on inkjet-printed silver electrodes.
AB  - For a rapid on-site diagnosis of pathogens, low-cost chip-based devices are of
      great interest. Here, we report the successful fabrication of inkjet printed
      silver electrodes on polymer foils as disposable chips for molecular DNA
      analytics. In order to manufacture these electrode structures, silver
      nanoparticle inks were inkjet printed onto planar polypropylene substrates. Due
      to the low thermal stability of the foils, substrate preserving sintering
      techniques, including low temperature thermal sintering and low pressure argon
      plasma sintering, were implemented. Thus, sufficient electrical conductance of
      the printed structures at processing temperatures <=100  degrees C was achieved.
      To test the applicability of the manufactured chips, specific capture DNA was
      immobilized within the gaps of the conductive electrode paths and hybridized in
      the next step with biotin-labeled target DNA. Subsequently, an enzymatically
      generated silver nanoparticle deposition was induced that bridges the electrode
      gap. This enabled both conductance measurement and gray value analysis as a fast,
      simple and robust electrical and optical read-out system. The proof-of-principle
      experiments successfully demonstrated the applicability of these convenient chip
      on-foil devices for nucleic acid based pathogen detection. 

PMID- 24276695
TI  - Intracameral recombinant tissue plasminogen activator (r-tPA) for refractory
      toxic anterior segment syndrome.
AB  - AIMS: To investigate the therapeutic effect of recombinant tissue plasminogen
      activator (r-tPA) in patients with refractory toxic anterior chamber segment
      syndrome after cataract surgery with posterior chamber intraocular lens
      implantation. METHODS: This prospective cohort study was performed from May 2010
      to November 2011 at a tertiary university-based medical centre. Forty patients
      (40 eyes) with an anterior chamber fibrin reaction after cataract surgery were
      treated with intracameral injection of r-tPA (25 ug/0.1 mL) following failure to
      respond to conventional treatment with intensive topical and subconjunctival
      steroids. Outcome measures were best-corrected visual acuity,
      clearance/recurrence of the fibrin reaction and complications. Corneal
      endothelial cell counts were evaluated before and after r-tPA injection (n=6).
      RESULTS: Intracameral r-tPA injection was administered 10-49 days after cataract
      surgery; mean was 20.3+/-9.6 days after surgery. At 1 day after treatment,
      complete clearance of the fibrin reaction was observed in 32 patients (80%) and
      partial clearance in 8 (20%). At the 1-month evaluation, the reaction had
      completely resolved in 95% of patients. Mean visual acuity improved from 0.61+/
      0.38 logMAR before treatment to 0.45+/-0.37 logMAR 1 month later (p=0.06). There
      were no statistically significant differences in improvement in visual acuity and
      fibrinolysis rate by time of r-tPA injection after surgery (10-15 days, n=16 vs
      16-49 days, n=24). There were no cases of increased intraocular pressure or
      endophthalmitis following the procedure. CONCLUSIONS: Intracameral injection of
      25 ug r-tPA is safe and effective for the treatment of refractory fibrin reaction
      after cataract surgery.

PMID- 24276696
TI  - Topical ophthalmic agents as allergens in periorbital dermatitis.
AB  - BACKGROUND: Allergic contact dermatitis is a leading cause of periorbital
      dermatitis. The extremely thin nature of the periorbital skin may facilitate
      allergen penetration, making this area particularly susceptible to allergic
      contact sensitisation. In this study, we assessed sensitisation rates to
      ingredients of common topical ophthalmic agents. MATERIALS AND METHODS: Data
      collected by 57 participating centres of the Information Network of Departments
      of Dermatology (IVDK) were analysed retrospectively. Of the 101,403 patients
      patch tested between January 2001 and December 2010, 4779 patients suffered from
      periorbital dermatitis and 1158 patients were specifically tested to the
      ophthalmic tray. Patch test results of the latter group were analysed in detail.
      RESULTS: The ophthalmic tray consisted of seven preservatives, six antibiotics
      and three other ophthalmic agents. Antibiotics (gentamicin, neomycin, kanamycin)
      were the leading group of allergens. Patch testing with preservatives often
      elicited irritant or weak positive reactions. CONCLUSIONS: When suspecting
      contact allergy in the periorbital area, patch testing should be considered in
      order to identify and avoid offending allergens. Testing to substances from a
      standardised ophthalmic tray is recommended, but it is preferable to test the
      actual drops or creams since many chemicals that are present in ophthalmics are
      not available as commercial test allergens. Given their wide use, preservatives
      cannot be regarded as common allergens, while antibiotics cause more often true
      allergic reactions necessitating a long-term avoidance.

PMID- 24276697
TI  - Retinal thinning and correlation with functional disability in patients with
      Parkinson's disease.
AB  - AIMS: To determine whether there is an association between retinal thinning and
      functional rating scales in patients with Parkinson's disease (PD). MATERIALS AND
      METHODS: Patients with PD (n=153) and controls (n=242) underwent evaluations of
      the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier
      domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec,
      Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg,
      Germany). PD severity was assessed using the Schwab-England Activities of Daily
      Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY)
      scale. Retinal and RNFL thicknesses were compared between patients and controls.
      Correlations between structural parameters and the scores of the neurologic
      scales were evaluated. RESULTS: RNFL parameters were significantly reduced in
      patients with PD, especially when using the Spectralis OCT device. All macular
      parameters, except for foveal thickness, differed significantly between controls
      and patients with PD (p<0.001). HY scores were significantly and inversely
      correlated with all macular parameters when measured with the Spectralis OCT
      device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device
      (nasal quadrant, sectors 2 and 5). CONCLUSIONS: The neurodegeneration caused by
      PD can be detected using Fourier domain OCT. RNFL and macular thicknesses
      correlate with PD severity.

PMID- 24276698
TI  - 22-gauge sclerotomy architecture evaluated by anterior segment optical coherence
      tomography.

PMID- 24276699
TI  - Bioelectric potential changes in the style of Lilium longiflorum Thunb. after
      self- and cross-pollination of the stigma.
AB  - Two different types of bioelectric potential changes have been registered in the
      style of Lilium longiflorum cv. Arai 5 after different treatments of the stigma.
      Self-pollination induces a bioelectric potential change different from the
      potential change induced by cross-pollination. Removal of the stigma or
      apllication of killed compatible pollen induced a bioelectrical response similar
      to the potential change recorded after cross-pollination. No bioelectric
      potential change was recorded after application of pollen of Petunia hybrida,
      pollen of Haemanthus katherinae, killed self-pollen, or no treatment at all.The
      mean generation time of the bioelectric potential change was 338 min after the
      treatment. The translocation velocity varied between 1.2 and 5.4 cm h(-1). Both
      responses are similar to the potential changes registered in Mimosa pudica after
      different types of stimulation and to the potential changes generated by the
      phytochrome in Avena coleoptiles. The translocation of the signals is discussed
      in relation to the models on the translocation in Mimosa. The relation between
      the bioelectric potential changes and the incompatibility reaction in Lilium
      longiflorum is discussed. 

PMID- 24276700
TI  - Paramylon synthesis by Euglena gracilis photoheterotrophically grown under low O2
      pressure : Description of a mitochloroplast complex.
AB  - Special culture conditions for Euglena gracilis Z and ZR are described. They
      induce interactions between the chloroplast and mitochondrial metabolisms leading
      to paramylon synthesis. When grown in continuous light under pure nitrogen and in
      the presence of lactate as the sole carbon source, sugar synthesis occurs during
      the first 24 h of culture with the participation of both mitochondria (using
      lactate) and of chloroplasts (fixing CO2 from lactate decarboxylation). The
      activities of ribulose bisphosphate carboxylase, phosphoenolpyruvate carboxylase,
      and phosphoenolpyruvate carboxykinase are very high and mitochondria and
      chloroplasts develop then a common network of vesicles in which paramylon grains
      can be seen. Electron micrographs demonstrate membrane continuity between the two
      types of organelles. Occasionally the mitochondrial matrix and the chloroplast
      stroma are separated by only a unit membrane. 

PMID- 24276701
TI  - Immunocytochemical study of phosphoenolpyruvate carboxylase in nodulated Alnus
      glutinosa.
AB  - The activities of phosphoenolpyruvate carboxylase (PEP carboxylase, EC 4.1.1.3.1)
      have been investigated in various organs of young nodulated Alnus glutinosa. The
      root nodules exhibited the highest specific enzyme activity when compared with
      the one in roots and leaves. Furthermore, in the root nodules the PEP carboxylase
      was predominantly localized in the cytosol of the large cortical cells containing
      the endophyte vesicles. 

PMID- 24276702
TI  - Glutamine synthetase of Chlamydomonas: its role in the control of nitrate
      assimilation.
AB  - Work is described which suggests that glutamine synthetase (GS) could play an
      important and direct regulatory role in the control of NO3 assimilation by the
      alga. In both steady-state cells and ones disturbed physiologically by changes in
      light or nitrogen supply the assimilation of NO3 appears to be limited by the
      activity of GS. Moreover although in normal cells NH3 can completely inhibit NO3
      uptake, promote the deactivation of nitrate reductase (NR) and repress the
      synthesis of NR and nitrite reductase (NIR), these controls are relaxed in cells
      in which GS is deactivated by treatment with L-methionine-DL-sulfoximine (MSO).
      It is proposed that the reversible deactivation of GS may play an important part
      in the regulation of NO3 assimilation although it is still not clear whether the
      enzyme itself or products of its metabolism are responsible. 

PMID- 24276703
TI  - Quantitative predictions for the chemiosmotic uptake of auxin.
AB  - 1. The predictions of a general kinetic model for the chemiosmotic uptake of
      auxin and other weak acids are compared with experimental results for the auxin
      indoleacetic acid. The proposed mechanism involves diffusional flux of
      undissociated acid, a saturable, voltage-sensitive flux of anion (A(-)), and a
      carrier-mediated symport of H(+) and A(-), all operating in parallel. During much
      of uptake, the electrochemical gradients are such that the net symport and the
      net anion flux are in opposition: the symport contributes more to influx; the
      anion path, to efflux. The voltage-sensitive flux of A(-) therefore constitutes a
      "leak". 2. The presence of a symport, whose carrier can distribute across the
      membrane in response to the internal and external concentrations of auxin, can
      speed the rate of uptake, but does not by itself alter the accumulation of auxin
      at equilibrium. 3. The accumulation ratio at equilibrium is less at low
      concentrations of auxin than at higher concentrations, indicating the presence of
      a saturable anion path. The concentration dependence of the transition depends on
      several factors, and is not a reliable indicator of the A(-)-carrier binding
      constant. 4. Observed uptake near neutral pH appears larger than is consistent
      with a voltage-sensitive anion flux being the only carrier-mediated path across
      the membrane. This observation provides indirect evidence for the presence of an
      auxin-proton symport in addition to a saturable A(-) carrier. 5. The change in
      kinetics of uptake of [(3)H]indole-3-acetic acid (IAA), observed as the total
      concentration of IAA is raised from 0.1 to 100 MUM, is consistent with either (i)
      a symport that saturates at low concentrations, or (ii) activation of an A(-)
      efflux by intermediate concentrations of auxin. 6. The data on the concentration
      dependence of uptake of auxin are not consistent with a multi-proton symport. 

PMID- 24276704
TI  - Assessment of glycinebetaine and proline compartmentation by analysis of isolated
      beet vacuoles.
AB  - Vacuoles isolated from storage root tissue of red beet (Beta vulgaris L.) do not
      leak significant quantities of betanin, sucrose, Na(+) or K(+) during isolation.
      This indicates that analysis of vacuoles in vitro gives meanigful information
      about the compartmentation of solutes in vivo. Preparations of vacouoles were
      used to determine the distribution of glycinebetaine and proline between vacuole
      and cytoplasm in beet cells. Both compounds were detected in preparations of
      isolated beet vacuoles. In the case of glycinebetaine it was shown that this
      solute was associated with the vacuoles, not with the small number of other
      organelles which contaminated the preparations. The vacuolar pool accounted for
      26 to 84% of the total tissue glycinebetaine and 17 to 57% of the proline.
      Concentrations of these compounds in vacuole and cytoplasm were calculated and
      were always higher in the cytoplasm than in the vacuole. The concentration
      gradient across the tonoplast varied considerably. The significance of these
      results is discussed in relation to the hypothesis that glycinebetaine and
      proline function as benign cytoplasmic osmotica. 

PMID- 24276705
TI  - Structure of grafted crown-gall teratoma shoots of tobacco: Regulation of
      transformed cells.
AB  - Crown-gall teratomas are tumors of higher plants with an intrinsic capacity for
      organogenesis. The growth pattern of tobacco (Nicotiana tabacum L.) teratoma
      shoots, which is highly aberrant in primary tumors, becomes normal when the
      shoots are grafted to healthy stock plants. However, certain abnormalities
      commonly persist; tumors form at the graft junctions, leaves are small, apical
      dominance is incomplete, the stem and proximal region of the leaf midribs swell
      excessively, and localized eruptions of neoplastic growth occur on the swollen
      tissue. Swelling of the shoots is primarily the result of cell hypertrophy in the
      cortex. Neoplastic divisions do not occur as a general rule; they are restricted,
      with the exception of tumor formation at the graft junctions, to localized
      eruptions of teratoid growth on the nodes and leaf midribs where cell hypertrophy
      is most evident. The histology of the apical meristem and histogenesis of primary
      tissues is normal, even in grossly distorted shoots. Similarly, there is no
      evidence of unregulated division in the vascular cambium. It is concluded that
      cell expansion and division are tightly regulated in meristematic regions of
      teratoma shoots whereas post-meristematic tissue is prone to excessive
      hypertrophy and eventual initiation of neoplastic cell division. 

PMID- 24276706
TI  - Ethylene formation from 1-aminocyclopropane-1-carboxylic acid by microsomal
      membranes from senescing carnation flowers.
AB  - Isolated membranes from the petals of senescing carnation flowers (Dianthus
      caryophyllus L. cv. White-Sim) catalyze the conversion of 1-aminocyclopropane-1
      carboxylic acid (ACC) to ethylene. A microsomal membrane fraction obtained by
      centrifugation at 131,000 g for 1 h proved to be more active than the membrane
      pellet isolated by centrifugation at 10,000 g for 20 min. The ethylene-producing
      activity of the microsomal membranes is oxygen-dependent, heat-denaturable,
      sensitive to n-propyl gallate, and saturable with ACC. Corresponding cytosol
      fractions from the petals are incapable of converting ACC to ethylene. Moreover,
      the addition of soluble fraction back to the membrane fraction strongly inhibits
      the ACC to ethylene conversion activity of the membranes. The efficiency with
      which isolated membranes convert ACC to ethylene is lower than that exhibited by
      intact flowers based on the relative yield of membranes per flower. This may be
      due to the presence of the endogenous soluble inhibitor of the reaction, for
      residual soluble fraction inevitably remains trapped in membrane vesicles
      isolated from a homogenate. 

PMID- 24276707
TI  - Translocation profiles of (11)C-assimilates in the petiole of Marsilea
      quadrifolia L.
AB  - An array of three multipliers with BGO-crystals arranged along the petiole has
      been used to study the movement of (11)C-assimilate in Marsilea quadrifolia L.
      The leaf blades were exposed to a 3-6 min pulse of (11)CO2 under continuous
      light. Data were recorded with 10-s counting intervals and corrected for
      background, sensitivity of detectors, and (11)C-decay. The speed of translocation
      could be obtained from the time difference between the straight lines of (11)C
      increase monitored at different positions along the petiole. The speed was within
      the range of 60 to 150 cm h(-1). Cutting as well as cold treatment at definite
      locations on the petiole led to an immediate stop of (11)C-movement. Both
      inhibition and-in the case of chilling-restoration of translocation were
      detectable within minutes. When the assimilation chamber was flushed with
      nitrogen gas, the normal increase of (11)C at the monitored sites slowed down
      which, after prolonged N2-treatment, even resulted in a decrease. With a time
      delay down the petiole, replacement of N2 by an air-stream led to complete
      restoration of the (11)C-slope. These and similar shortterm effects on
      translocation could not be detected by former methods. This technique is also
      useful in with species other than Marsilea qu., which was chosen as a test plant
      because of the anatomical 'simplicity' of its petiole. 

PMID- 24276708
TI  - Development and storage-protein synthesis in Brassica napus L. embryos in vivo
      and in vitro.
AB  - Immature embryos of Brassica napus were cultured in vitro with and without
      various concentrations of germination inhibitors, and the progress of embryogeny
      was monitored by comparing accumulation of storage proteins in culture with the
      normal accumulation in seeds. The two major B. napus storage proteins (12S and
      1.7S) were purified from seed extracts and analyzed by rocket
      immunoelectrophoresis (12S protein) or by sodium lauryl sulfate polyacrylamide
      gel electrophoresis (1.7S protein). During embryo development within seeds both
      the 12S and 1.7S proteins were first detected when the cotyledons were well
      developed (embryo dry weight, 0.4 mg), and each storage protein accumulated at an
      average rate of 26 MUg d(-1) during maximum deposition. Accumulation of the 1.7S
      protein stopped when the water content of the embryo began to decline (embryo DW,
      2.7 mg), but accumulation of the 12S protein continued until seed maturity
      (embryo DW, 3.6 mg). At the end of embryo development the 12S and the 1.7S
      proteins comprised approx. 60 and 20% of the total salt-soluble protein,
      respectively. When embryos were removed from seeds at day 27, just as storage
      protein was starting to accumulate, and placed in culture on a basal medium, they
      precociously germinated within 3d, and incorporation of amino acids into the 12S
      storage protein dropped from 3% of total incorporation to less than 1%. If 10(-6)
      M abscisic acid (ABA) was included in the medium, amino-acid incorporation into
      the 12S protein increased from 3% of total incorporation when embryos were placed
      into culture to 18%, 5d later, and the accumulation rate (27.1+/-2.6 MUg embryo(
      1) d(-1)) matched the maximum rate observed in the seed. High osmotica, such as
      0.29 M sucrose or mannitol, added to the basal medium, also inhibited precocious
      germination, but there was a lag period before 12S-protein synthesis rates
      equaled the rates on ABA media. These results indicate that some factor in the
      seed environment is necessary for storage-protein synthesis to proceed, and that
      ABA is a possible candidate. 

PMID- 24276709
TI  - Isolation of biochemical mutants using haploid mesophyll protoplasts of
      Hyoscyamus muticus : I. A NO 3 (-) non-utilizing clone.
AB  - A population of 3070 clones derived from N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG)-treated mesophyll protoplasts of haploid Hyoscyamus muticus was tested for
      amino-acid auxotrophy without enrichment. One clone (MA-2) was stably and
      specifically dependent on casein hydrolysate and could be fed also by a number of
      single amino acids or by other reduced nitrogen sources. MA-2 was found to be
      chlorate resistant and devoid of in vivo nitrate reductase activity under
      inductive conditions. Permissive and restrictive growth conditions for MA-2 were
      investigated more closely and media were found promoting morphogenesis. Selection
      and testing of clones were complicated by an unspecific growth stimulation of
      some wild type cultures by amino acids, thiamine and m-inositol. 

PMID- 24276710
TI  - Isolation of biochemical mutants using haploid mesophyll protoplasts of
      Hyoscyamus muticus : II. Auxotrophic and temperature-sensitive clones.
AB  - The total isolation procedure for isolation of auxotrophic and temperature
      sensitive mutants was applied to haploid mesophyll protoplasts of Hyoscyamus
      muticus after treatment with N-methyl-N'-nitro-N-nitrosoguanidine. Twelve variant
      clones were isolated after screening a total of 29,000 clones. Two are
      auxotrophic for histidine, one clone for tryptophan and three clones for
      nicotinamide. Two clones that grow only in presence of a group of amino acids
      including glutamine and asparagine are also ClO 3 (-) resistant. Two further
      clones have as yet undefined amino-acid requirements. Two temperature-sensitive
      clones were found, one of which stops growing at the restrictive temperature of
      32 degrees C and the other undergoes chlorosis and accumulates an insoluble brown
      pigment. All clones expressed consistently the variant phenotypes in many retests
      and characterisation experiments over more than one year. Shoots have been
      regenerated from the nicotinamide- and histidine-requiring clones and from one
      temperaturesensitive clone. Two control (wild-type) morphogenic clones were used:
      one green and the other more variably pigmented and showing some growth
      stimulation in presence of medium supplements. 

PMID- 24276711
TI  - Liposome-mediated delivery of DNA to carrot protoplasts.
AB  - The encapsulation of DNA within liposomes and subsequent fusion of the liposomes
      with carrot (Daucus carota L.) protoplasts were examined to determine optimum
      conditions for effective liposome-mediated delivery of DNA to protoplasts.
      Escherichia coli [(3)H]DNA could be encapsulated with 50% efficiency using
      encapsulation volumes as low as 0.5 ml. Incorporation of liposome-encapsulated
      [(3)H]DNA by carrot protoplasts increased linearly for 2.5 h, and increasing the
      ratio of protoplasts to liposomes increased the total amount of radioactive label
      incorporated within the protoplasts. Liposome-mediated incorporation of [(3)H]DNA
      by protoplasts increased over a range of polyethylene glycol concentrations up to
      20%, but Ca(2+) did not increase liposome-mediated incorporation when present in
      the liposome-protoplast incubation mixture. Optimum incorporation was observed
      when the pH of the liposome-protoplast incubation medium was decreased to 4.8.
      Encapsulation experiments using DNA of the plasmid pBR322 indicated that an
      average of 200-1,000 intact copies of pBR322 were sequestered within each nucleus
      after liposome delivery. 

PMID- 24276712
TI  - An EXAFS and HR-XANES study of the uranyl peroxides [UO2(eta2-O2)(H2O)2].nH2O (n
      = 0, 2) and uranyl (oxy)hydroxide [(UO2)4O(OH)6].6H2O.
AB  - The solid-sate structures of the two uranyl peroxides studtite, [UO2(eta(2)
      O2)(H2O)2].2H2O, and metastudtite [UO2(eta(2)-O2)(H2O)2] have been determined by
      U-L3 edge extended X-ray absorption fine structure (EXAFS) spectroscopy and show
      that upon removal of the interstitial water in studtite there are structural
      changes with a small shortening of the U-O(peroxo) and small lengthening of the U
      O(yl) bonds. High-energy resolution X-Ray absorption near edge structure (HR
      XANES) spectroscopy has been used to probe the differences in the local
      electronic structure and, supported by ab initio FEFF9.5.1 calculations,
      dehydration causes a shift to higher energies of the occupied O p-DOS and U d-
      and f-DOS of metastudtite. The HR-XANES spectrum of schoepite,
      [(UO2)4O(OH)6].6H2O, has been measured as the White Line intensity can give
      information on the mixing of metal and ligand atomic orbitals. There is an
      indication for higher degree of ionicity for the U-OH bond in schoepite compared
      to the U-O2 bond in studtite.

PMID- 24276713
TI  - Comment: About this issue.

PMID- 24276714
TI  - Prevention in a free society.
AB  - While knowledge required for prevention can be derived from epidemiological
      studies, additional effort is needed from economists, behavioral scientists, and
      others to explore the costs of different health problems, the cost of
      intervention, and benefits, and the social acceptability of the activity. The
      tendency of health professionals is to apply medical techniques to prevention
      without exploring the efficacy, efficiency, or acceptability of nonmedical
      alternatives. The overall results of nationally sponsored prevention efforts have
      been disappointing. An attempt to align public prevention expenditures with
      objectively derived priorities provokes a question as to whether planning and
      priority setting for prevention can be done efficiently in the United States. 

PMID- 24276715
TI  - Prevention/promotion with minorities.
AB  - This article analyzes preventive/promotive strategies whereby minority persons
      (with special reference to black Americans) can build on their collective
      strengths and prevent predictable problems. 

PMID- 24276716
TI  - Ecological strategies of prevention in rural community development.
AB  - Preventive strategies within the framework of an ecological paradigm combine
      elements of theory, ideology, and practice method, among others. The theory
      posits a relationship between socially integrated community systems and wellness,
      both physical and mental. The ecological focus on adaptation constrains an
      ideological emphasis on health and on the natural caring function of the
      "informal economy." Practice strategies focus on the design of supportive
      environments that enhance competence and that maximize the utilization of natural
      social processes for the achievement of preventive ends. 

PMID- 24276718
TI  - Bringing outsiders In: "Visions and realities".

PMID- 24276717
TI  - Adaptation of children of parents suffering from cancer: A preliminary study of a
      new field for primary prevention research.
AB  - An important new field for primary prevention research is proposed: the
      adaptation of normal children to the stress of normal parents who suffer from
      cancer. A pilot retrospective investigation of adolescent daughters of mothers
      who has mastectomy for breast cancer revealed a high level of motivation to
      participate in the study. Most girls were significantly upset and felt
      inadequately supported during periods of peak stress in their mothers caused by
      the illness and its treatment. Prospective studies are proposed that will develop
      and evaluate methods to ameliorate suffering and to lower the risk of
      psychopathology in children of parents with cancer. 

PMID- 24276719
TI  - Saving children's lives: The ultimate award.

PMID- 24276720
TI  - Primary prevention program clearinghouse psychology department-Dewey Hall
      University of Vermont, Burlington, VT. 05405.

PMID- 24276721
TI  - Erratum.

PMID- 24276723
TI  - Arabic melodic and rhythmic therapy. A method of severe aphasia therapy.
AB  - The necessity of a therapy allowing aphasics to be rehabilitated quickly in
      social life urged us to adapt a therapeutic strategy developed in the USA and
      implemented in France under 'therapie melodique et rythmee'. This model of
      language therapy has been destined to aphasics with good auditory comprehension
      and emotional stability despite severe language impairment. A careful evaluation
      of the patient is necessary to select the candidates for exposure to this
      therapy. Our evaluation is based on an examination battery (made of repetition,
      naming, auditory comprehension), items inspired by the Boston Diagnostic Aphasia
      Examination and adapted to Tunisian context. This method relies on the prosodic
      features of Tunisian Arabic (melody patterns, rhythm, pitch, stress ....) and
      proceeds from non verbal exercises. The latter are realised by a corpus of texts
      of various length and structure. Applying Arabic melodic and rhythmic therapy
      allowed patients to recover the capacity to communicate to different degrees with
      others. 

PMID- 24276724
TI  - Principles and applications of echo planar imaging in magnetic resonance.
AB  - Echo planar imaging was initially introduced as a technique to reduce the
      magnetic resonance imaging exam to a single shot (snap-shot) acquisition, much
      like a conventional radiograph. This vision, of course, created a good deal of
      speculation about the clinical impact of an echo planar imaging-equipped magnetic
      resonance imaging device. From completing the entire magnetic resonance exam in a
      matter of seconds to expanding the applications field of magnetic resonance
      imaging into territories traditionally claimed by other modalities, the perceived
      potential of echo planar imaging was indeed great. It was not until this decade,
      however, that the technical challenges involved with developing echo planar
      imaging into a clinical tool have been overcome. 

PMID- 24276722
TI  - A biophysically based finite-state machine model for analyzing gastric
      experimental entrainment and pacing recordings.
AB  - Gastrointestinal motility is coordinated by slow waves (SWs) generated by the
      interstitial cells of Cajal (ICC). Experimental studies have shown that SWs
      spontaneously activate at different intrinsic frequencies in isolated tissue,
      whereas in intact tissues they are entrained to a single frequency. Gastric
      pacing has been used in an attempt to improve motility in disorders such as
      gastroparesis by modulating entrainment, but the optimal methods of pacing are
      currently unknown. Computational models can aid in the interpretation of complex
      in vivo recordings and help to determine optimal pacing strategies. However,
      previous computational models of SW entrainment are limited to the intrinsic
      pacing frequency as the primary determinant of the conduction velocity, and are
      not able to accurately represent the effects of external stimuli and electrical
      anisotropies. In this paper, we present a novel computationally efficient method
      for modeling SW propagation through the ICC network while accounting for
      conductivity parameters and fiber orientations. The method successfully
      reproduced experimental recordings of entrainment following gastric transection
      and the effects of gastric pacing on SW activity. It provides a reliable new tool
      for investigating gastric electrophysiology in normal and diseased states, and to
      guide and focus future experimental studies. 

PMID- 24276725
TI  - Childhood enuresis. Epidemiology, pathophysiology and management.
AB  - The goal of this article is to review childhood enuresis, which is a common
      behavioral condition reported in millions of children worldwide. An online
      computer search was made, and the literature up to 1997 was screened in order to
      include relevant data for this review. The prevalence of childhood enuresis
      varies across reviewed studies. This was attributed to a variety of
      sociodemographic and cultural dynamics of societies. Similarly, the
      pathophysiology of this ubiquitous symptom is determined by multiple risk factors
      including biological, psychological, social, and cultural, but the
      developmental/maturational delay influenced by genetics remains the most
      plausible explanation. Although a variety of pharmacological and non
      pharmacological treatment modalities are traced in the literature, there is yet
      no agreement on a single strategy. A general agreement about behavioral therapy
      as the first choice of treatment of this minor malady began to emerge.
      Additionally, tricyclic antidepressants are the most frequently prescribed drugs
      for the treatment of childhood enuresis. Enuresis is a pediatric public health
      problem and concerted efforts at all levels, ie, professional, promotional,
      educational and public should be made to address its multiple domains such as
      preventive, etiological and curative. 

PMID- 24276726
TI  - Cricopharyngeal myotomy in neurogenic oropharyngeal dysphagia.
AB  - OBJECTIVE: Cricopharyngeal myotomy as an independent procedure has been performed
      on fourteen patients with a variety of neuromuscular disorders, suffering from
      neurogenic oropharyngeal dysphagia in the interval between 1994-1997. All of them
      were referred from a neurophysician or physiatrist after failure of improvement
      by medical treatment. METHODS: The selection of patients for operation was based
      mainly on clinical evaluation and simple exclusion criteria without manometric
      studies. RESULTS: There was dramatic improvement in twelve, with recurrent
      laryngeal nerve palsy and temporary pharyngeal fistula in two patients. No
      mortality was recorded. CONCLUSION: We conclude that cricopharyngeal myotomy is a
      simple, safe and effective procedure with acceptable morbidity. It should be
      considered as a rehabiliation procedure for patients with dysphagia due to
      various neurologic disorders based on simple, clinical exclusion criteria without
      the need for the tedious, time consuming and expensive manometric studies.

PMID- 24276727
TI  - Subclinical diabetic neuropathy. A common complication in Saudi diabetics.
AB  - OBJECTIVE: To determine the prevalence of sub clinical diabetic neuropathy in
      Saudi diabetics and the risk factors associated with symptomatic diabetic
      neuropathy. METHODS: A prospective study of Saudi diabetics attending King
      Abdulaziz University Hospital out patient clinic from January 1998 until April
      1999. Detailed information of each patients' age, sex, body mass index, type and
      duration of diabetes mellitus, mode of treatment, degree of blood glucose
      control, presence of hypertension, hyperlipidemia, smoking, family history of
      diabetes mellitus and hypertension were recorded. Patients were assessed for
      diabetic neuropathy using the Michigan Neuropathy Program. Patients who were
      asymptomatic and scored less than 2 on simple clinical examination were referred
      to a neurologist for a complete neurological examination and nerve conduction
      studies. RESULTS: A total of 237 patients were studied with a mean age of 54.19
      years and mean duration of diabetes 10.6 years. Symptomatic diabetic neuropathy
      was present in 132 (56%) patients while subclinical neuropathy was present in 58
      (57%) of asymptomatic patients. Old age, type II diabetes with long duration,
      poor control and smoking were risk factors associated with symptomatic diabetic
      neuropathy (p<0.001, p=0.09, p<0.001, p=0.04, p=0.08). CONCLUSION: Subclinical
      diabetic neuropathy is common. Early diagnosis is important for possible
      prevention of late neuropathic complications (foot ulcers and infections).
      Prolonged poorly controlled diabetes mellitus, old age and smoking are risk
      factors for symptomatic diabetic neuropathy. Meticulous blood glucose control is
      important for nerve function protection. Researches are urgently needed for
      satisfactory therapy.

PMID- 24276728
TI  - The use of indomethacin for the prevention of intraventricular brain hemorrhage
      in high-risk neonates.
AB  - OBJECTIVE: The objective of this study was to determine the effect of
      indomethacin on reducing the incidence of intraventricular hemorrhage in
      premature infants treated in our units at King Faisal Specialist Hospital and
      Research Centre. METHODS: This historical cohort study included 45 infants born
      with birth weights of 1250g or less and received indomethacin in the first 12
      hours of life for intraventricular hemorrhage prevention. The treated infants
      were compared to 33 other infants with birth weights of 1250g or less who did not
      receive indomethacin for intraventricular hemorrhage prevention. Data collected
      included demographic, complications of prematurity, renal function and maternal
      data. RESULTS: Mean birth weight (grams) and gestational age (week) were 928.4+/
      34, 1066.2+/-38.9, 27.2+/-0.37 and 29+/-0.42 for the treated and the control
      infants. Overall incidence of intraventricular hemorrhage decreased significantly
      in the treated infants in comparison to the controls (P=0.0169). There was no
      infant with Grade 3-4 intraventricular hemorrhage found in the treated group
      while 2 developed grade 3-4 intraventricular in the control group which was
      insignificant. There were no statistically significant differences between the
      groups in terms of the complications of prematurity, Apgar scores at 5 minutes,
      airleak syndrome and the use of umbilical catheters. The total fluid intake in
      the first 4 days after starting the treatment was comparable between the groups.
      There were no significant differences between the groups in urine output in day
      1, 3 and 4. However the urine output decreased significantly in day 2 in the
      treated group (P = 0.0349). There were no statistically significant differences
      in serum urea and creatinine between the groups CONCLUSION: Low dose indomethacin
      given in the first 12 hours of life was shown to be associated with a decrease in
      intraventricular hemorrhage in premature infants and it was not associated with
      significant adverse effect.

PMID- 24276729
TI  - Subdural hematoma complicating middle fossa arachnoid cyst.
AB  - We report a case of a middle aged patient with middle fossa arachnoid cyst that
      was complicated by subdural hematoma. This was demonstrated by magnetic resonance
      imaging that remain the most useful diagnostic tool, and providing excellent
      tissue specificity. Patient was treated by irrigating the hematoma through
      burrholes. Magnetic resonance imaging in the postoperative period showed a
      reduction in size of the arachnoid cyst. 

PMID- 24276730
TI  - Neuromuscular weakness and Type II respiratory failure as a result of chronic and
      intermediate organophsophate poisoning.
AB  - We report 3 cases with generalized neuromuscular weakness and Type II
      hypercapnoeic respiratory failue as a result of respiratory muscle weakness. This
      proved to be due to intoxication with organophosphate insecticides. 

PMID- 24276731
TI  - A fatal pseudallescheria boydii brain abscess.
AB  - We present the clinical and radiological features of pseudallescheria boydii
      infection in a middle aged woman who presented with right frontal
      pseudallescheria abscess after two years use of prednisolone for rheumatoid
      arthritis. Despite early surgical excision and intravenous antifungal treatment
      she died after 7 weeks despite aggressive therapy. 

PMID- 24276732
TI  - In-patient treatment for resistant obsessive-compulsive disorder.
AB  - Obsessive Compulsive Disorder is one of the increasing psychological disorders.
      If not detected early and treated properly, obsessive-compulsive disorder usually
      becomes an incapacitating illness adversely affecting almost all aspects of the
      patient's life. Outpatient behavioral and pharmacotherapies frequently fail. This
      is a report on a severe case of obsessive-compulsive disorder that was treated as
      an in-patient with both behavior and pharmacotherapies, she was then followed up
      for 5 years with no relapse. The case reflects the importance and the need for in
      patient units for severe resistant obsessive compulsive cases especially in Saudi
      Arabia where we have an increasing number of such cases. 

PMID- 24276733
TI  - Intracranial tuberculoma.
AB  - Six patients with cerebral tuberculoma seen over a 2 year period are reported.
      Their clinical presentations, the result of investigations including radiological
      findings and their response to medical treatment are discussed and correlated
      with other reports in the literature. Eighty five percent of the patients were
      above the age of 30 years. All patients had negative past history of tuberculosis
      and both chest x-ray and erythrocyte sedimentation rate were within normal
      limits. Five patients presented with symptoms and signs of space occupying
      lesions but none had papilloedema. Two patients showed paradoxical enlargement or
      development of new tuberculous lesions during antituberculous therapy. The
      diagnosis was established by brain magnetic resonance imaging in 3 patients, and
      was further confirmed by brain biopsy in the other 3. All patients received
      antituberculous treatment for 12 months, except one who continued medication for
      2 years. Four patients normalized with medical treatment. Intracranial
      tuberculoma must be included in the differential diagnosis of a space occupying
      lesion. Magnetic resonance imaging is a sensitive, non-invasive method to
      diagnose cerebral tuberculoma. Paradoxical enlargement or development of new
      tuberculomas during antituberculous therapy is a documented phenomenon which can
      be overcome by continuation of antituberculous treatment. Twelve months of
      antituberculous treatment is considered to be adequate to resolve intracranial
      tuberculoma. 

PMID- 24276734
TI  - Methods of treatment for back pain and sciatica.

PMID- 24276735
TI  - Characterization of an organic solvent-tolerant lipase from Idiomarina sp. W33
      and its application for biodiesel production using Jatropha oil.
AB  - A halophilic strain W33 showing lipolytic activity was isolated from the saline
      soil of Yuncheng Salt Lake, China. Biochemical and physiological characterization
      along with 16S rRNA gene sequence analysis placed the isolate in the genus
      Idiomarina. The extracellular lipase was purified to homogeneity by 75% ammonium
      sulphate precipitation, DEAE-Sepharose anion exchange and Sephacryl S-200 gel
      filtration chromatography. The molecular mass of the purified lipase was
      estimated to be 67 kDa by SDS-PAGE. Substrate specificity test indicated that it
      preferred long-chain p-nitrophenyl esters. Optimal lipase activity was found to
      be at 60  degrees C, pH 7.0-9.0 and 10% NaCl, and it was highly active and stable
      over broad temperature (30-90  degrees C), pH (7.0-11.0) and NaCl concentration
      (0-25%) ranges, showing excellent thermostable, alkali-stable and halotolerant
      properties. Significant inhibition by diethyl pyrocarbonate and phenylarsine
      oxide was observed, implying histidine and cysteine residues were essential for
      enzyme catalysis. In addition, the lipase displayed high stability and activity
      in the presence of hydrophobic organic solvents with log P(ow) >= 2.13. The free
      and immobilized lipases produced by Idiomarina sp. W33 were applied for biodiesel
      production using Jatropha oil, and about 84 and 91% of yields were achieved,
      respectively. This study formed the basic trials conducted to test the
      feasibility of using lipases from halophile for biodiesel production.

PMID- 24276736
TI  - WITHDRAWN:C677T Methylenetetrahydrofolate reductase gene polymorphism in
      schizophrenia and bipolar disorder.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 24276738
TI  - Cytogenetics of the trigeneric hybrid, (Hordeum vulgare *Triticum aestivum)
      *Secale cereale.
AB  - Chromosome pairing was studied in hybrids of (Hordeum vulgare *Triticum aestivum)
      *Secale cereale. Chiasma frequency per cell varied from 1.94 to 3.16 between the
      different hybrids. This variation was attributed to genetic variability in rye
      parents which affected homoeologous pairing. The pairing of rye chromosomes as
      revealed by Giemsa C-banding was a combination of nonhomologous association
      between rye chromosomes and associations with chromosomes of wheat and barley. 

PMID- 24276737
TI  - Somaclonal variation - a novel source of variability from cell cultures for plant
      improvement.
AB  - It is concluded from a review of the literature that plant cell culture itself
      generates genetic variability (somaclonal variation). Extensive examples are
      discussed of such variation in culture subclones and in regenerated plants
      (somaclones). A number of possible mechanisms for the origin of this phenomenon
      are considered. It is argued that this variation already is proving to be of
      significance for plant improvement. In particular the phenomenon may be employed
      to enhance the exchange required in sexual hybrids for the introgression of
      desirable alien genes into a crop species. It may also be used to generate
      variants of a commercial cultivar in high frequency without hybridizing to other
      genotypes. 

PMID- 24276739
TI  - Peroxidase and leucine-aminopeptidase in diploidMedicago species closely related
      to alfalfa: Multiple gene loci, multiple allelism, and linkage.
AB  - The genetics of peroxidase and leucine-aminopeptidase isozymes was studied
      utilizing starch gel electrophoresis in the diploidsMedicago sativa L. (M.
      coerulea Less.) andM. falcata L. Three anodal and one cathodal sets of peroxidase
      isozymes identify four linked loci. In addition, two anodal sets of leucine
      aminopeptidase isozymes identify two loci that may be linked. The allozymes at
      each of the loci segregated as expected for monomeric enzymes. However in several
      crosses there were deficiencies in the number of progeny in particular genotypic
      classes. This could result from the segregation of recessive deleterious genes
      linked to some of the allozyme alleles. This is the first report of multiple loci
      and multiple alleles determining isozymes inMedicago. 

PMID- 24276740
TI  - Structural and genetical studies on the high-molecular-weight subunits of wheat
      glutenin : Part 1: Allelic variation in subunits amongst varieties of wheat
      (Triticum aestivum).
AB  - The high-molecular-weight (HMW) subunits of glutenin from about 185 varieties
      were fractionated by sodium dodecyl sulphate polyacrylamide gel electrophoresis
      (SDS-PAGE). About 20 different, major subunits were distinguished by this
      technique although each variety contained, with only a few exceptions, between 3
      and 5 subunits. Further inter-varietal substitution lines to those already
      described (Payne et al. 1980) were analysed and the results indicate that all the
      HMW subunits are controlled by the homoeologous group 1 chromosomes. All
      hexaploid varieties studied except 'NapHal' contained two major subunits
      controlled by chromosome 1D. Their genes were shown to be tightly linked
      genetically for only four different types of banding patterns were observed. The
      nominal molecular weights determined after fractionation in 10% polyacrylamide
      gels were between 110,000 and 115,000 for the larger of the two subunits and
      between 82,000 and 84,000 for the smaller. One quarter of the varieties contained
      only one major HMW subunit controlled by chromosome 1B whereas the rest had two.
      The chromosome 1B subunits were the most varied and nine different banding
      patterns were detected. All the subunits had mobilities which were intermediate
      between those of the two chromosome 1D-controlled subunits. Only two types of HMW
      subunit controlled by chromosome 1A were detected in all the varieties examined;
      a single variety never contained both of these subunits and 40% of varieties
      contained neither. The chromosome 1A-controlled subunits had slightly slower
      mobilities in 10% gels than the largest HMW subunit controlled by chromosome 1D.
      About 100 single grains were analysed from each of five different crosses of the
      type (F1 of variety A * variety B) * variety C. The results indicate that the
      genes on chromosome 1B which control the synthesis of subunits 6, 7, 13, 14 and
      17 are allelic, as are the genes of the chromosome 1A-controlled subunits, 1 and
      2. 

PMID- 24276741
TI  - Linkage relationships between genes controlling seed proteins in French bean.
AB  - The inheritance of phaseolin and globulin-2 (G2)/albumin polypeptides was
      investigated in crosses involving varieties which exhibited the three
      electrophoretic banding patterns of phaseolin found in French bean. 'Total' seed
      protein extracts of single seeds of the F1 and F2 generations from the crosses:
      'Sanilac' * 'Contender', 'BBL 240' * 'Contender', and 'Sanilac' * 'BBL 240' were
      analyzed by two-dimensional electrophoresis. Segregation of the genes controlling
      phaseolin and G2/albumin polypeptides, and those controlling a further five
      groups of seed proteins (A, B, D, E, and F) were observed. No recombinant
      electrophoretic phenotypes were seen for phaseolin or G2/albumin polypeptides
      suggesting that the genes controlling each of these groups of polypeptides are
      closely linked and segregate like single Mendelian genes. The phaseolin genes and
      G2/albumin genes were not linked to each other. The group of genes controlling
      phaseolin polypeptides were linked to those controlling group B proteins, and
      those controlling G2/albumin polypeptides were linked to those controlling group
      F proteins. 

PMID- 24276742
TI  - The higher plant cell: Potentials and limitations.

PMID- 24276743
TI  - A two loci viability matrix with implications in current population genetics
      models.
AB  - Some equilibrium properties of a two loci deterministic system subject to a
      postulated viability matrix are given. Two conclusions are reached: i) linkage
      can not stabilize additive equally contributing two-loci systems under optimizing
      selection. ii) Hybrid protein superiority can not be invoked for the maintenance
      of polymorphisms shared by duplicated structural loci. 

PMID- 24276744
TI  - Accumulating evidence for statins in primary prevention.

PMID- 24276746
TI  - Some health paradoxes.

PMID- 24276745
TI  - Overuse of papanicolaou testing among older women and among women without a
      cervix.

PMID- 24276747
TI  - Self psychology in pastoral counseling.
AB  - This article provides a general explication of how a pastoral counselor might use
      the self psychology perspective in conjunction with theological and ethical
      approaches. A particularly appropriate structure for this explication is self
      psychology's theory and practice of psychoanalytic psychotherapy as a two-phase
      process: an observation-understanding phase, in which empathic introspection is
      the central method, and an explanation-interpretation phase, in which by these
      empathic means the therapist hopes to consolidate further and mobilize
      developmentally an individual or group's self-cohesion. Each of these phases and
      the self psychology theory behind them provide an organizing rubric by which we
      can discuss how theological and ethical approaches might be carried out in a
      working alliance with the self psychology framework. 

PMID- 24276748
TI  - Karma and redemption: A religious approach to family violence.
AB  - Violence within the family is becoming so widespread that its treatment cannot be
      left to specialists alone, but increasingly will be faced by the helping
      professions generally. The Hindu concept of Karma and the Christian theory of
      redemption together provide a religious understanding for those who seek to help
      both the perpetrators and victims of family violence. Karma holds the truth that
      actions bear consequences, whereas redemption suggests that the evil consequences
      can be altered for good. The result is a new Karmic law which provides a
      fundamental starting point for family abuse counseling. 

PMID- 24276749
TI  - Possession as role-taking.
AB  - The paper discusses the psychological function of mythical roles in the genesis
      and maintenance of the possessional experience. The Devil as a personification of
      the evil provides a "role" which is possible to recognize and even interiorize.
      Theemotional psychological dynamics interacts with thecognitive content provided
      by the religious world-view. A case is analyzed and related to prior scientific
      studies in the field bordering psychopathology and pastoral experience. 

PMID- 24276750
TI  - Religious experience and public cult: The case of Mary Ann Van Hoof.
AB  - This study focuses on the first year (1950) of the apparitions of the Virgin Mary
      reported by Mary Ann Van Hoof of Necedah, Wisconsin. It argues that Van Hoof's
      experiences met not simply the needs of the community-at-large, but also helped
      the seer draw meaning from an emotionally-deprived and abusive childhood. The
      study concludes by suggesting that public serial apparitions are complex events
      that should be examined for the light they shed on the interaction between the
      seer's personal characteristics and experiences and the public events that take
      shape around those experiences. 

PMID- 24276751
TI  - Dying: A universal human experience?
AB  - This paper explores the question, "Is there a universal psychological experience
      suffered by all dying persons?" a question to which the popular theory of Kubler
      Ross presupposes an affirmative answer. Our answer takes three steps: first, a
      comparison between the Kubler-Ross model of dying and that of the late
      medievalBook of the Craft of Dying centered upon the five Kubler-Ross "stages";
      second, a philosophical critique of the terms of this comparison; and third, a
      revised look at the alleged similarities between the two models, providing a
      deeper look at the moral and spiritual assumptions behind each. 

PMID- 24276752
TI  - A sermon from hell: Toward a theology of loneliness.
AB  - Loneliness as part of the human condition is first explored from an experiential
      philosophical perspective. A biblical survey suggests loneliness is normative to
      the faith experience and may portray a more "realistic" religiosity. Desert
      imagery in Scripture indicates a strong association among solitude, spiritual
      development, and potential dangers of spiritual deception. God's "not yet-ness"
      itself a cause of existential loneliness-is paradoxically the way in which
      communion with God functions in the here and now. The creative use of solitude
      may enhance social, psychological, and spiritual well-being, and provide a way to
      theologize about personal isolation and disorientation. 

PMID- 24276753
TI  - Involvement of the nuclear factor-kappaB pathway in the adhesion of neutrophils
      to renal tubular cells after injury induced by neonatal postasphyxial serum.
AB  - Nuclear factor kappaB (NF-kappaB) plays an important role in the regulation of
      inflammatory proteins. However, it is unclear whether the NF-kappaB/intercellular
      adhesion molecule-1 (ICAM-1) pathway is involved in the adhesion of neutrophils
      and renal injury after hypoxia-ischemia (HI) in neonates. In this report we
      investigated whether NF-kappaB and its downstream molecule ICAM-1 were involved
      in renal injury induced by postasphyxial serum (PS) from neonates. Human renal
      proximal tubular (HK-2) cells were preincubated with 10 % fetal calf serum
      (control), 20 % neonatal PS, or 20 % PS plus pyrolidine dithiocarbamate (PDTC).
      The expression of IkappaBalpha, NF-kappaB p65, and ICAM-1 in HK-2 cells was
      determined by Western blot and/or immunohistochemistry. Nuclear translocation of
      NF-kappaB p65 in HK-2 cells was detected by immunofluorescence and Western blot.
      The ICAM-1 mRNA was determined by RT-PCR. Then HK-2 cells were cultured with
      neutrophils from neonates with asphyxia. After HK-2 cells had been cultured with
      neutrophils, we detected myeloperoxidase (MPO) activity, the leakage rate of
      lactate dehydrogenase (LDH), and cell viability. We found that PS preincubation
      resulted in significantly decreased IkappaBalpha expression and increased
      expression of NF-kappaB and ICAM-1, and facilitated the nuclear translocation of
      NF-kappaB in HK-2 cells. PS preincubation increased MPO activity, leading to
      elevated leakage rates of LDH and decreased cell viability after neutrophil
      exposure. Furthermore, the inhibition of NF-kappaB activity by PDTC significantly
      upregulated IkappaBalpha expression, decreased NF-kappaB and ICAM-1 expression,
      downregulated the nuclear translocation of NF-kappaB, and decreased MPO activity.
      This leads to decreased leakage rates of LDH and increased cell viability after
      neutrophil exposure. Our findings suggest that NF-kappaB/ICAM-1 pathway may be
      involved in neutrophil-endothelial interactions and neonatal renal injury after
      HI. 

PMID- 24276754
TI  - Activation of prosurvival signaling pathways during the memory phase of volatile
      anesthetic preconditioning in human myocardium: a pilot study.
AB  - According to a compelling body of evidence anesthetic preconditioning (APC)
      attenuates the deleterious consequences of ischemia-reperfusion and protects the
      heart through a mechanism similar to ischemic preconditioning. The present study
      was purported to investigate the intracellular signaling pathways activated in
      human myocardium in response to a preconditioning protocol with two different
      volatile anesthetics, namely isoflurane and sevoflurane. To this aim,
      phosphorylation of PKCalpha and -delta, ERK1/2, Akt, and GSK3beta was determined
      at the end of the APC protocol, in human atrial samples harvested from patients
      undergoing open-heart surgery. The results demonstrate that preconditioning with
      volatile anesthetics triggers the activation of PKCdelta and -alpha isoforms and
      of prosurvival kinases, ERK1/2, and Akt, while inhibiting their downstream target
      GSK3beta during the memory phase. 

PMID- 24276755
TI  - miR-141 suppresses proliferation and motility of gastric cancer cells by
      targeting HDGF.
AB  - miR-141 belongs to the miR-200 family, and has been found to be associated with
      numerous human malignancies; however, its role in gastric cancer (GC) has not
      been examined in detail. Here, we validated that miR-141 was decreased in GC
      tissues and cell lines. Forced expression of miR-141 significantly repressed GC
      cell proliferation and colony formation. Furthermore, miR-141 suppressed in vitro
      migration and invasion of GC cells. Hepatoma-derived growth factor (HDGF) was
      confirmed to be a direct target of miR-141 in GC cells. The suppressive effects
      of miR-141 on GC cell proliferation, colony formation, in vitro migration, and
      invasion were partially mediated by suppressing HDGF expression. Moreover, the
      expression of HDGF was negatively correlated with miR-141 in GC tissues. Our data
      suggest that miR-141 might be associated and plays essential role in GC
      progression. 

PMID- 24276756
TI  - Soluble expression of proteins correlates with a lack of positively-charged
      surface.
AB  - Prediction of protein solubility is gaining importance with the growing use of
      protein molecules as therapeutics, and ongoing requirements for high level
      expression. We have investigated protein surface features that correlate with
      insolubility. Non-polar surface patches associate to some degree with
      insolubility, but this is far exceeded by the association with positively-charged
      patches. Negatively-charged patches do not separate insoluble/soluble subsets.
      The separation of soluble and insoluble subsets by positive charge clustering
      (area under the curve for a ROC plot is 0.85) has a striking parallel with the
      separation that delineates nucleic acid-binding proteins, although most of the
      insoluble dataset are not known to bind nucleic acid. Additionally, these basic
      patches are enriched for arginine, relative to lysine. The results are discussed
      in the context of expression systems and downstream processing, contributing to a
      view of protein solubility in which the molecular interactions of charged groups
      are far from equivalent. 

PMID- 24276757
TI  - Image acquisition and interpretation criteria for 99mTc-HMPAO-labelled white
      blood cell scintigraphy: results of a multicentre study.
AB  - PURPOSE: There is no consensus yet on the best protocol for planar image
      acquisition and interpretation of radiolabelled white blood cell (WBC)
      scintigraphy. This may account for differences in reported diagnostic accuracy
      amongst different centres. METHODS: This was a multicentre retrospective study
      analysing 235 WBC scans divided into two groups. The first group of scans (105
      patients) were acquired with a fixed-time acquisition protocol and the second
      group (130 patients) were acquired with a decay time-corrected acquisition
      protocol. Planar images were interpreted both qualitatively and
      semiquantitatively. Three blinded readers analysed the images. RESULTS: The most
      accurate imaging acquisition protocol comprised image acquisition at 3 - 4 h and
      at 20 - 24 h in time mode with acquisition times corrected for isotope decay.
      CONCLUSION: Using this protocol, visual analysis had high sensitivity and
      specificity in the diagnosis of infection. Semiquantitative analysis could be
      used in doubtful cases, with no cut-off for the percentage increase in
      radiolabelled WBC over time, as a criterion to define a positive scan.

PMID- 24276758
TI  - Mobilisation of the major stored reserves in the embryo of fenugreek (Trigonella
      foenum-graecum L., Leguminosae), and correlated enzyme activities.
AB  - Changes in total nitrogen, soluble amino nitrogen, lipid and phytate contents,
      and in the activities of proteinase (pH 7.0), isocitrate lyase and phytase were
      followed in the endosperm, cotyledons, and axis during germination of fenugreek
      seeds and subsequent growth of the seedlings. The endosperm is comprised largely
      of cell-wall galactomannans: the majority of the seed total nitrogen, lipid and
      phytate (5%, 8%, 0.44% of seed dry weight respectively) is localised within the
      cotyledons as stored reserves. Germination is completed after 10-14 h from the
      start of imbibition, but the major reserves are not mobilised during the first 24
      h. Then the total nitrogen content of the cotyledons starts to decrease and that
      of the axis increases; there is a concomitant accumulation of soluble amino
      nitrogen in both cotyledons and axis. An increase in proteinase activity in the
      cotyledons correlates well with the depletion of total nitrogen therein.
      Depletion of lipid and phytate reserves in the different seed tissues constitutes
      a late event, occurring after 50 h from the start of imbibition, and is
      coincident with the final disintegration of the endosperm tissue. The depletion
      of phytate and stored lipids is accompanied by an increase in phytase and
      isocitrate lyase activity. It appears that the products of lipid hydrolysis are
      converted by gluconeogenesis to serve as the major source of sugars for the
      growing axis after the endosperm galactomannan has been completely mobilised. 

PMID- 24276759
TI  - Phytochrome action in light-grown plants: the influence of light quality and
      fluence rate on extension growth in Sinapis alba L.
AB  - Using light-grown plants of Sinapis alba an analysis has been made of the effect
      on extension growth of adding far red light to a background photosynthetic
      source. It has been possible to distinguish between the increase in fluence rate
      and the reduction of the amount of phytochrome present as Pfr, which are both
      consequences of the addition of supplementary far red light, and to determine
      that the response of increased extension growth is due only to the latter. It is
      shown that the degree of fluence rate dependency varies with photoequilibrium and
      the significance of this interaction is discussed in terms of the mode of action
      of phytochrome and of its role in the natural light environment. 

PMID- 24276760
TI  - The influence of light quality on the phytochrome content of light grown Sinapis
      alba L. and Phaseolus aureus Roxb.
AB  - The effect on the phytochrome system of light regimes establishing a range of
      photoequilibria was studied in two light grown dicotyledonous plants, both of
      which were treated with the herbicide SAN 9789 to prevent chlorophyll
      accumulation. In Sinapis alba L. cotyledons the results are comparable with
      phytochrome behaviour in etiolated mustard seedlings; the level of Pfr becomes
      independent of wave-length whereas the total phytochrome level is wave-length
      dependent. Contrasting properties are exhibited in Phaseolus aureus Roxb. leaves
      in which total phytochrome is unaffected by light quality; consequently the Pfr
      level is dependent on wavelength. Nevertheless, the amount of phytochrome in mung
      leaves increased after transfer to darkness suggesting that light still has a
      profound influence on the phytochrome system, even though light quality during
      the light period and prior to darkness does not. 

PMID- 24276761
TI  - Tissue-specific antigens secreted by suspension-cultured callus cells of Prunus
      avium L.
AB  - A number of antigenic components are secreted into the medium by P. avium callus
      cells derived from different tissues and grown in suspension culture. These
      antigens have been detected using antiserum raised in rabbits to a protein
      fraction secreted by P. avium leaf callus. One antigen is specific to leaf tissue
      and is secreted by callus cells derived from stem, pistil and anthers as well as
      leaves. A second antigen is, in intact organs, restricted to styles of a
      particular self-incompatibility (S) genotype, but is also secreted by callus
      cells derived from the leaf. Another antigen, apparently not organ-specific, is
      secreted by all calli tested, including Rosa (cv. Paul's Scarlet). 

PMID- 24276762
TI  - Style antigens of Prunus avium L.
AB  - Antiserum to a protein fraction of an extract of mature styles of P. avium cv.
      Lambert (S 3 S 4) was raised in rabbits. Two major antigenic components of the
      style extracts were detected by immunoelectrophoresis and immunodiffusion. The
      presence of one antigen (S-antigen) correlated with a particular S-genotype (S 3
      S 4). This antigen is restricted to mature styles of P. avium. The second antigen
      (P-antigen) was detected in styles of all Prunus species examined, but not in
      styles of other species of the Rosaceae. The S-antigen is positively charged and
      the P-antigen negatively charged at pH 8.8. 

PMID- 24276763
TI  - Expression of storage-protein genes during soybean seed development.
AB  - Mature seeds of Glycine max (L.) Merr. contain two major storage proteins, a
      glycosylated 7S protein (conglycinin) and a non-glycosylated 11S protein
      (glycinin). Accumulation of these proteins and their mRNAs during seed
      development in cv. Provar was studied by SDS polyacrylamide gel electrophoresis
      and by "Northern" (DNA-RNA) hybridization. The 11S acidic and basic subunits and
      the 7S alpha' and alpha subunits began to accumulate 18-20 d after pollination,
      shortly after the termination of cell division in developing cotyledons, whereas
      the 7S beta and 11S A-4 subunits were not detected until one to two weeks later,
      during the maturation phase of development. Messenger RNAs for 7S and 11S
      proteins were first detected 14-18 d after pollination, several days before the
      accumulation of storage proteins. Extracts from embryonic axes contained reduced
      levels of the 7S alpha subunit, very little 11S protein, no detectable 7S beta or
      11S A-4 subunits, and an additional 7S subunit not found in cotyledons. Soybean
      axes and cotyledons therefore differ in their synthesis of seed storage proteins.

PMID- 24276764
TI  - Characterisation of a salt-stimulated ATPase activity associated with vacuoles
      isolated from storage roots of red beet (Beta vulgaris L.).
AB  - Ion stimulation and some other properties of an ATPase activity associated with
      vacuoles isolated from storage roots of red beet (Beta vulgaris L.) have been
      determined. The ATPase had a specific requirement for Mg(2+) and in the presence
      of Mg(2+) it was stimulated by salts of monovalent cations. The degree of
      stimulation by monovalent salts was influenced mainly by the anion and the order
      of effectiveness of the anions tested was Cl(-)>HCO 3 (-) >Br(
      )>malate>acetate>SO 4 (2-) . For any given series of anions the magnitude of the
      stimulation obtained was influenced by the accompanying cation (NH 4 (+) ?
      Na(+)>K(+)). This cation effect was abolished by 0.01% (v/v) Triton X-100 and it
      is suggested that it is the result of different permeabilities of membrane
      vesicles to the cations. There was no evidence of synergistic stimulation of the
      ATPase by mixtures of Na(+) and K(+). KCl- and NaCl-stimulation was maximal with
      salt concentrations in the range 60-150 mM. The true substrate of the enzyme was
      shown to be MgATP. It was shown that KCl stimulation was the result of an
      increase in Vmax rather than a change in the affinity of the enzyme for MgATP.
      The ATPase was inhibited by N,N'-dicyclohexylcarbodiimide, diethylstilbestrol,
      mersalyl and KNO3 but other inhibitors tested (azide, oligomycin, orthovanadate,
      K3[Cr(oxalate)6] and ethyl-3-[3-dimethylaminopropyl]carbodiimide) were without
      effect or caused only partial inhibition at the highest concentration tested. The
      ATPase activity was equally distributed between pellet and supernatant fractions
      obtained after the subfractionation of vacuoles but the properties of the ATPase
      in each fraction were the same. It is suggested that beet vacuoles possess only
      one ATPase. The properties of the ATPase are compared with those of ATPases
      associated with other plant membranes and organelles and its possible role in
      transport at the tonoplast is discussed. 

PMID- 24276765
TI  - Mg(2+)-Dependent, cation-stimulated inorganic pyrophosphatase associated with
      vacuoles isolated from storage roots of red beet (Beta vulgaris L.).
AB  - Vacuoles isolated from storage roots of red beet (Beta vulgaris L.) posess a
      Mg(2+)-dependent, alkaline pyrophosphatase (PPase) activity which is further
      stimulated by salts of monovalent cations. The requirement for Mg(2+) is
      specific. Mn(2+) and Zn(2+) permitted only 20% and 12%, respectively, of the
      PPase activity obtained in the presence of Mg(2+) while Ca(2+), Co(2+) and Cu(2+)
      were ineffective. Stimulation of Mg(2+)-PPase activity by salts of certain
      monovalent cations was due to the cation and the order of effectiveness of the
      cations tested was K(+)=Rb(+)=NH 4 (+) >Cs(+). Salts of Li(+) and Na(+) inhibited
      Mg(2+)-PPase activity by 44% and 24%, respectively. KCl-stimulation of Mg(2+)
      PPase activity was maximal with 60-100 mM KCl. There was a sigmoidal relationship
      between PPase activity and Mg(2+) concentrations which resulted in markedly non
      linear Lineweaver-Burk plots. At pH 8.0, the optimal [Mg(2+)]:[PPi] ratio for
      both Mg(2+)-PPase and (Mg(2+)+KCl)-PPase activities was approximately 1:1, which
      probably indicates MgP2O7 (2-) is the true substrate. 

PMID- 24276766
TI  - Synthesis and metabolism of abscisic acid in detached leaves of Phaseolus
      vulgaris L. after loss and recovery of turgor.
AB  - Metabolism of abscisic acid (ABA) was studied after wilting and upon recovery
      from water stress in individual, detached leaves of Phaseolus vulgaris L. (red
      kidney bean). Loss of turgor was correlated with accumulation of ABA and its
      metabolites, resulting in a 10-fold increase in the level of phaseic acid (PA)
      and a doubling of the level of conjugated ABA. The level of conjugated ABA in
      turgid leaves was no higher than that of the free acid. These results indicate
      that accumulation of ABA in wilted leaves resulted from a stimulation of ABA
      synthesis, rather than from a release from a conjugated form or from inhibition
      of the metabolism of ABA. The rate of synthesis of ABA was at its maximum between
      2.5 and 5 h after turgor was lost, and slackened there-after. In wilted leaves,
      the rate of conversion of ABA to PA climbed steadly until it matched the rate of
      synthesis, after about 7.5 h. Upon rehydration of sections from wilted leaves,
      the rate of synthesis of ABA dropped close to zero within about 3 h, while the
      rate of conversion to PA accelerated. Formation of PA was two to four times
      faster than in sections maintained in the wilted condition; it reached a rate
      sufficient to convert almost one-half of the ABA present in the tissue to PA
      within 1 h. In contrast, the alternate route of metabolism of ABA, synthesis of
      conjugated ABA, was not stimulated by rehydration. The role of turgor in the
      stimulation of the conversion of ABA to PA was investigated. When leaves that had
      been wilted for 5 h were rehydrated to different degrees, the amount of ABA which
      disappeared, or that of PA which accumulated during the next 3 h, did not depend
      linearly on the water potential of the rehydrated leaf. Rather, re-establishment
      of the slightest positive turgor was sufficient to result in maximum stimulation
      of conversion of ABA to PA. 

PMID- 24276767
TI  - Proline accumulation in a barley mutant resistant to trans-4-hydroxy-L-proline.
AB  - Five proline analogues were tested for inhibition of the growth of mature barley
      (Hordeum vulgare L.) embryos in sterile culture. Inhibition by all analogues was
      relieved by proline. Inhibition by trans-4-hydroxy-L-proline was relieved by low
      amounts of proline. Twenty thousand mature embryos were dissected from M2 seeds
      after sodium azide mutagenesis. Four plants (Rothamsted 5201, 6102, 6901, 6902)
      were selected with good growth on 4 mM trans-4-hydroxyproline. Properties of
      mutant R5201 were studied in detail. Selfed progeny of R5201 were all resistant
      to trans-4-hydroxyproline and also to L-thiazolidine-4-carboxylic acid and trans
      3-hydroxy-L-proline but not L-azetidine-2-carboxylic acid. The content of soluble
      proline in progeny of R5201 was higher in leaves by a factor of up to six-fold.
      Proline content was measured in the soluble fraction of the terminal 20 mm of 4 d
      old plants subjected to severe water stress in 40% w/v polyethylene glycol.
      Leaves of the mutant contained more proline initially and accumulated proline
      morer rapidly than the parental leaves. As mutant leaves were larger and lost
      water more rapidly the greater increase in proline may have been caused by more
      severe water stress. Resistance to trans-4-hydroxyproline in R5201 was due to a
      single partially dominant nuclear gene. 

PMID- 24276768
TI  - The effect of light and dark periods on the production of ethylene from water
      stressed wheat leaves.
AB  - Light was found to inhibit substantially (i.e. up to 88%) the production of
      ethylene induced by water stress in excised wheat leaves and from the shoots of
      intact plants. The relatively small amounts of ethylene emanating fron non
      stressed leaves were also inhibited by light but to a smaller degree (i.e. up to
      61%). In water-stressed leaves the degree of light inhibition of ethylene
      production was shown to be related to the age of the leaves; the amounts of
      ethylene diffusing from young leaves (i.e. 6-days old) was inhibited 52% by light
      whereas in older leaves (i.e. 9-days old) it was inhibited by 85%. Previous
      studies [Wright (1979) Planta 144, 179-188 and (1980) Planta 148, 381-388] had
      shown that application of 6-benzyladenine (BA) to leaves a day before wilting,
      greatly increases the amount of ethylene diffusing from the leaves following
      wilting (e.g. 8-fold), and to smaller degrees do applications of indole-3-acetic
      acid (IAA) and gibberellic acid (GA3). On the other hand abscisic acid (ABA)
      treatment reduces the amount of ethylene produced. In these earlier experiments
      the ethylene was collected from leaves held under dark or near-dark conditions,
      so in the present study the activities of these growth regulators (10(-4) mol l(
      1) solutions) under dark and light conditions were compared. It was found that
      they maintained the same relative activities on ethylene emanation (i.e.
      BA>IAA>GA3>water controls>ABA) under both light and dark conditions. However,
      because of the inhibitory effect of light, the absolute amounts of ethylene
      produced from all treatments were always much higher in the dark than in the
      light (usually about a 6-fold difference). An interesting effect of light
      treatment on ethylene biosynthesis was found when water-stressed leaves were kept
      in dark chambers for 41/2 h and then transferred to light. Quite unexpectedly,
      instead of the rate of ethylene production falling immediately, it continued to
      be produced at the dark rate (i.e. no light inhibition!) for over 2 h before the
      rate began to decline, and for a much longer period (i.e. in excess of 41/2 h) if
      the leaves had previously been sprayed with BA. Predictably, leaves placed in the
      light (i.e. in leaf chambers) and then transferred to darkness, immediately or
      very soon produced ethylene at the dark rate. One explanation of these results,
      which is discussed, would be that the biosynthesis of an ethylene precursor
      requires an obligatory dark stage. The possible implications of these studies to
      a survival role of ethylene in plants during periods of water stress is
      discussed. 

PMID- 24276769
TI  - The mechanism of sugar uptake by sugarcane suspension cells.
AB  - Sugarcane cell suspensions took up sugar from the medium at rates comparable to
      or greater than sugarcane tissue slices or plants in the field. This system
      offers an opportunity for the study of kinetic and energetic mechanisms of sugar
      transport in storage parenchyma-like cells in the absence of heterogeneity
      introduced by tissues. The following results were obtained: (a) The sugar uptake
      system was specific for hexoses; as previously proposed, sucrose was hydrolyzed
      by an extracellular invertase before the sugar moieties were taken up; no
      evidence for multiple sugar uptake systems was obtained. - (b) Uptake of the
      glucose-analog 3-O-methylglucose (3-OMG) reached a plateau value with an
      intracellular concentration higher than in the medium (approximately 15-fold). -
      (c) There was a balance of influx and efflux during steady state; the rate of
      exchange influx was lower than the rate of net influx; the Km value was higher
      (70 MUM) than for net influx (24 MUM); the exchange efflux is proposed to be
      mediated by the same transport system with a Km value of approximately 2.6 mM for
      internal 3-OMG; the rate of net efflux of hexoses was less than a third of the
      rate of exchange efflux. - (d) The uptake of hexoses proceeded as proton-symport
      with a stoichiometry of 0.87 H(+) per sugar; during the onset of hexose transport
      there was a K(+) exit of 0.94 K(+) per sugar for charge compensation. (It was
      assumed that the "real" stoichiometries are 1 H(+) and 1 K(+) per sugar.) The Km
      values for sugar transport and sugar-induced proton uptake were identical.
      Sucrose induced proton uptake only in the presence of cell wall invertase. - (e)
      There was no net proton uptake with 3-OMG by cells which were preloaded with
      glucose though there was significant sugar uptake. It is assumed, therefore, that
      the exit of hexose occurs together with protons. - (f) The protonmotive potential
      of sugarcane cells corresponded to about 120 mV: pH-gradient 1.1 units, membrane
      potential of-60 mV (these values increased if vacuolar pH and membrane potential
      were also considered). It was abolished by uncouplers, and the magnitude of the
      components depended on the external pH value. We present evidence for the
      operation of a proton-coupled sugar transport system in cell suspensions that
      were derived from, and have characteristics of, storage parenchyma. The
      quantitative rates of sugar transport suggest that the role of this transport
      system is not limiting for sugar storage. 

PMID- 24276770
TI  - Seasonal reliance on nectar by an insectivorous bat revealed by stable isotopes.
AB  - Many animals have seasonally plastic diets to take advantage of seasonally
      abundant plant resources, such as fruit or nectar. Switches from insectivorous
      diets that are protein rich to fruits or nectar that are carbohydrate rich
      present physiological challenges, but are routinely done by insectivorous
      songbirds during migration. In contrast, insectivorous bat species are not known
      to switch diets to consume fruit or nectar. Here, we use carbon stable isotope
      ratios to establish the first known case of a temperate bat species consuming
      substantial quantities of nectar during spring. We show that pallid bats
      (Antrozous pallidus) switch from a diet indistinguishable from that of sympatric
      insectivorous bat species in winter (when no cactus nectar is present) to a diet
      intermediate between those of insectivorous bats and nectarivorous bats during
      the spring bloom of a bat-adapted cactus species. Combined with previous results
      that established that pallid bats are effective pollinators of the cardon cactus
      (Pachycereus pringlei), our results suggest that the interaction between pallid
      bats and cardon cacti represents the first-known plant-pollinator mutualism
      between a plant and a temperate bat. Diet plasticity in pallid bats raises
      questions about the degree of physiological adaptations of insectivorous bats for
      incorporation of carbohydrate-rich foods, such as nectar or fruit, into the diet.

PMID- 24276771
TI  - Genotypic diversity of an invasive plant species promotes litter decomposition
      and associated processes.
AB  - Following studies that showed negative effects of species loss on ecosystem
      functioning, newer studies have started to investigate if similar consequences
      could result from reductions of genetic diversity within species. We tested the
      influence of genotypic richness and dissimilarity (plots containing one, three,
      six or 12 genotypes) in stands of the invasive plant Solidago canadensis in China
      on the decomposition of its leaf litter and associated soil animals over five
      monthly time intervals. We found that the logarithm of genotypic richness was
      positively linearly related to mass loss of C, N and P from the litter and to
      richness and abundance of soil animals on the litter samples. The mixing
      proportion of litter from two sites, but not genotypic dissimilarity of mixtures,
      had additional effects on measured variables. The litter diversity effects on
      soil animals were particularly strong under the most stressful conditions of hot
      weather in July: at this time richness and abundance of soil animals were higher
      in 12-genotype litter mixtures than even in the highest corresponding one
      genotype litter. The litter diversity effects on decomposition were in part
      mediated by soil animals: the abundance of Acarina, when used as covariate in the
      analysis, fully explained the litter diversity effects on mass loss of N and P.
      Overall, our study shows that high genotypic richness of S. canadensis leaf
      litter positively affects richness and abundance of soil animals, which in turn
      accelerate litter decomposition and P release from litter. 

PMID- 24276772
TI  - Fatty acid and stable isotope characteristics of sea ice and pelagic particulate
      organic matter in the Bering Sea: tools for estimating sea ice algal contribution
      to Arctic food web production.
AB  - We determined fatty acid (FA) profiles and carbon stable isotopic composition of
      individual FAs (delta(13)CFA values) from sea ice particulate organic matter (i
      POM) and pelagic POM (p-POM) in the Bering Sea during maximum ice extent, ice
      melt, and ice-free conditions in 2010. Based on FA biomarkers, differences in
      relative composition of diatoms, dinoflagellates, and bacteria were inferred for
      i-POM versus p-POM and for seasonal succession stages in p-POM. Proportions of
      diatom markers were higher in i-POM (16:4n-1, 6.6-8.7%; 20:5n-3, 19.6-25.9%) than
      in p-POM (16:4n-1, 1.2-4.0%; 20:5n-3, 5.5-14.0%). The dinoflagellate marker 22:6n
      3/20:5n-3 was highest in p-POM. Bacterial FA concentration was higher in the
      bottom 1 cm of sea ice (14-245 MUg L(-1)) than in the water column (0.6-1.7 MUg
      L(-1)). Many i-POM delta(13)C(FA) values were higher (up to ~100/00) than those
      of p-POM, and i-POM delta(13)C(FA) values increased with day length. The higher i
      POM delta(13)C(FA) values are most likely related to the reduced dissolved
      inorganic carbon (DIC) availability within the semi-closed sea ice brine channel
      system. Based on a modified Rayleigh equation, the fraction of sea ice DIC fixed
      in i-POM ranged from 12 to 73%, implying that carbon was not limiting for primary
      productivity in the sympagic habitat. These differences in FA composition and
      delta(13)C(FA) values between i-POM and p-POM will aid efforts to track the
      proportional contribution of sea ice algal carbon to higher trophic levels in the
      Bering Sea and likely other Arctic seas.

PMID- 24276773
TI  - The allocation of assimilated carbon to shoot growth: in situ assessment in
      natural grasslands reveals nitrogen effects and interspecific differences.
AB  - In grasslands, sustained nitrogen loading would increase the proportion of
      assimilated carbon allocated to shoot growth (A shoot), because it would decrease
      allocation to roots and also encourage the contribution of species with
      inherently high A shoot. However, in situ measurements of carbon allocation are
      scarce. Therefore, it is unclear to what extent species that coexist in
      grasslands actually differ in their allocation strategy or in their response to
      nitrogen. We used a mobile facility to perform steady-state (13)C-labeling of
      field stands to quantify, in winter and autumn, the daily relative photosynthesis
      rate (RPR~tracer assimilated over one light-period) and A shoot (~tracer
      remaining in shoots after a 100 degree days chase period) in four individual
      species with contrasting morpho-physiological characteristics coexisting in a
      temperate grassland of Argentina, either fertilized or not with nitrogen, and
      either cut intermittently or grazed continuously. Plasticity in response to
      nitrogen was substantial in most species, as indicated by positive correlations
      between A shoot and shoot nitrogen concentration. There was a notable
      interspecific difference: productive species with higher RPR, enhanced by
      fertilization and characterized by faster leaf turnover rate, allocated ~20% less
      of the assimilated carbon to shoot growth than species of lower productivity (and
      quality) characterized by longer leaf life spans and phyllochrons. These results
      imply that, opposite to the expected response, sustained nitrogen loading would
      change little the A shoot of grassland communities if increases at the species
      level are offset by decreases associated with replacement of 'low RPR-high A
      shoot' species by 'high RPR-low A shoot' species.

PMID- 24276774
TI  - Transmembrane molecular transport through nanopores formed by protein nanotubes.
AB  - Protein nanotubes formed by layer-by-layer (LbL) assembly can penetrate cells and
      act as nanopores for direct transmembrane delivery of chemical compounds. 

PMID- 24276775
TI  - Performance of two geriatric screening tools in older patients with cancer.
AB  - PURPOSE: To compare the diagnostic characteristics of two geriatric screening
      tools (G8 and Flemish version of the Triage Risk Screening Tool [fTRST]) to
      identify patients with a geriatric risk profile and to evaluate their prognostic
      value for functional decline and overall survival (OS). PATIENTS AND METHODS:
      Patients >= 70 years old with a malignant tumor were included if a new cancer
      event occurred requiring treatment decision. Geriatric screening with G8 and
      fTRST (cutoff >= 1 [fTRST (1)] and >= 2 [fTRST (2)] evaluated) was performed in
      all patients, as well as a geriatric assessment (GA) evaluating social situation,
      functionality (activities of daily living [ADL] + instrumental activities of
      daily living [IADL]), cognition, depression, and nutrition. Functionality was re
      evaluated 2 to 3 months after cancer treatment decision, and death rate was
      followed. Functional decline and OS were evaluated in relation to normal versus
      abnormal score on both screening tools. RESULTS: Nine hundred thirty-seven
      patients were included (October 2009 to July 2011). G8 and fTRST (1) showed high
      sensitivity (86.5% to 91.3%) and moderate negative predictive value (61.3% to
      63.4%) to detect patients with a geriatric risk profile. G8 and fTRST (1) were
      strongly prognostic for functional decline on ADL and IADL, and G8, fTRST (1),
      and fTRST (2) were prognostic for OS (all P < .001). G8 had the strongest
      prognostic value for OS (hazard ratio for G8 normal v abnormal, 0.38; 95% CI,
      0.27 to 0.52). CONCLUSION: Both geriatric screening tools, G8 and fTRST, are
      simple and useful instruments in older patients with cancer for identifying
      patients with a geriatric risk profile and have a strong prognostic value for
      functional decline and OS.

PMID- 24276776
TI  - Preoperative magnetic resonance imaging assessment of circumferential resection
      margin predicts disease-free survival and local recurrence: 5-year follow-up
      results of the MERCURY study.
AB  - PURPOSE: The prognostic relevance of preoperative high-resolution magnetic
      resonance imaging (MRI) assessment of circumferential resection margin (CRM)
      involvement is unknown. This follow-up study of 374 patients with rectal cancer
      reports the relationship between preoperative MRI assessment of CRM staging,
      American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with
      overall survival (OS), disease-free survival (DFS), and time to local recurrence
      (LR). PATIENTS AND METHODS: Patients underwent protocol high-resolution pelvic
      MRI. Tumor distance to the mesorectal fascia of <= 1 mm was recorded as an MRI
      involved CRM. A Cox proportional hazards model was used in multivariate analysis
      to determine the relationship of MRI assessment of CRM to survivorship after
      adjusting for preoperative covariates. RESULTS: Surviving patients were followed
      for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM
      compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of
      1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to
      73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI
      involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence
      HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved
      CRM was the only preoperative staging parameter that remained significant for OS,
      DFS, and LR on multivariate analysis. CONCLUSION: High-resolution MRI
      preoperative assessment of CRM status is superior to AJCC TNM-based criteria for
      assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is
      significantly associated with distant metastatic disease; therefore, colorectal
      cancer teams could intensify treatment and follow-up accordingly to improve
      survival outcomes.

PMID- 24276777
TI  - Nurse navigators in early cancer care: a randomized, controlled trial.
AB  - PURPOSE: To determine whether a nurse navigator intervention improves quality of
      life and patient experience with care for people recently given a diagnosis of
      breast, colorectal, or lung cancer. PATIENTS AND METHODS: Adults with recently
      diagnosed primary breast, colorectal, or lung cancer (n = 251) received either
      enhanced usual care (n = 118) or nurse navigator support for 4 months (n = 133)
      in a two-group cluster randomized, controlled trial with primary care physicians
      as the units of randomization. Patient-reported measures included the Functional
      Assessment of Cancer Therapy-General (FACT-G) Quality of Life scale, three
      subscales of the Patient Assessment of Chronic Illness Care (PACIC), and selected
      subscales from a cancer adaptation of the Picker Institute's patient experience
      survey. Self-report measures were collected at baseline, 4 months, and 12 months.
      Automated administrative data were used to assess time to treatment and total
      health care costs. RESULTS: There were no significant differences between groups
      in FACT-G scores. Nurse navigator patients reported significantly higher scores
      on the PACIC and reported significantly fewer problems with care, especially
      psychosocial care, care coordination, and information, as measured by the Picker
      instrument. Cumulative costs after diagnosis did not differ significantly between
      groups, but lung cancer costs were $6,852 less among nurse navigator patients.
      CONCLUSION: Compared with enhanced usual care, nurse navigator support for
      patients with cancer early in their course improves patient experience and
      reduces problems in care, but did not differentially affect quality of life.

PMID- 24276778
TI  - Patient navigation improves the care experience for patients with newly diagnosed
      cancer.

PMID- 24276779
TI  - Impact of wait times on survival for women with uterine cancer.
AB  - PURPOSE: To determine whether wait time from histologic diagnosis of uterine
      cancer to time of definitive surgery by hysterectomy had an impact on all-cause
      survival. PATIENTS AND METHODS: Women in Ontario with a confirmed histopathologic
      diagnosis of uterine cancer between April 1, 2000, and March 31, 2009, followed
      by surgery were identified in the Ontario Cancer Registry. Survival was
      calculated by using the Kaplan-Meier method. Factors were evaluated for their
      prognostic effect on survival by using Cox proportional hazards regression. Wait
      time was evaluated in a multivariable model after adjusting for other significant
      factors. RESULTS: The final study population included 9,417 women; 51.9% had
      surgery by a gynecologist, and 69.9% had endometrioid adenocarcinoma. Five-year
      survival for women with wait times of 0.1 to 2, 2.1 to 6, 6.1 to 12, or more than
      12 weeks was 71.1%, 81.8%, 79.5%, and 71.9%, respectively. Wait times of <= 2
      weeks were adversely prognostic for survival after adjusting for other
      significant factors in the multivariable model, and patients with wait times of
      more than 12 weeks had worse survival than those who had wait times between 2.1
      and 12.0 weeks. CONCLUSION: To the best of our knowledge, this is the first
      report in a large population-based cohort demonstrating that longer wait times
      from diagnosis of uterine cancer to definitive surgery have a negative impact on
      overall survival.

PMID- 24276780
TI  - Mounting evidence for prediagnostic use of statins in reducing risk of lethal
      prostate cancer.

PMID- 24276782
TI  - Comment: Unemployment and mental health.

PMID- 24276781
TI  - Taking up physical activity in later life and healthy ageing: the English
      longitudinal study of ageing.
AB  - BACKGROUND: Physical activity is associated with improved overall health in those
      people who survive to older ages, otherwise conceptualised as healthy ageing.
      Previous studies have examined the effects of mid-life physical activity on
      healthy ageing, but not the effects of taking up activity later in life. We
      examined the association between physical activity and healthy ageing over 8
      years of follow-up. METHODS: Participants were 3454 initially disease-free men
      and women (aged 63.7 +/- 8.9 years at baseline) from the English Longitudinal
      Study of Ageing, a prospective study of community dwelling older adults. Self
      reported physical activity was assessed at baseline (2002-2003) and through
      follow-up. Healthy ageing, assessed at 8 years of follow-up (2010-2011), was
      defined as those participants who survived without developing major chronic
      disease, depressive symptoms, physical or cognitive impairment. RESULTS: At
      follow-up, 19.3% of the sample was defined as healthy ageing. In comparison with
      inactive participants, moderate (OR, 2.67, 95% CI 1.95 to 3.64), or vigorous
      activity (3.53, 2.54 to 4.89) at least once a week was associated with healthy
      ageing, after adjustment for age, sex, smoking, alcohol, marital status and
      wealth. Becoming active (multivariate adjusted, 3.37, 1.67 to 6.78) or remaining
      active (7.68, 4.18 to 14.09) was associated with healthy ageing in comparison
      with remaining inactive over follow-up. CONCLUSIONS: Sustained physical activity
      in older age is associated with improved overall health. Significant health
      benefits were even seen among participants who became physically active
      relatively late in life.

PMID- 24276783
TI  - Psychopathology, prevention, and the just society.
AB  - The problem of defining mental disorders is examined and models to explain
      emotional disturbances are considered. Arguments against a sickness explanation
      are advanced, and definitions of mental health are reviewed. All of these
      concerns lead into a discussion of primary prevention. Sources of opposition to
      prevention efforts include those persons committed to organic models, to one-to
      one intervention, and those who oppose social change efforts as inappropriate for
      mental health workers. An agenda for community change is proposed. 

PMID- 24276784
TI  - Primary prevention: Up the revolution!
AB  - In a recent article George Albee stated that the fourth mental health revolution
      was on the verge of beginning. This revolution would be primary prevention
      oriented. The present article examines evidence that such a revolution is
      underway or ready to begin and concludes that the evidence is not strong for such
      a position. A continuing problem is that the front-line personnel in community
      mental health centers do not appear to know what primary prevention is, and, even
      if they do, they are under pressure to provide fee-for-service treatment to
      individuals. Suggestions are made to remedy this situation. 

PMID- 24276785
TI  - Preventive mental health work with the elderly: With special reference to
      Asian/Pacific populations.
AB  - With the emergence of primary prevention as a major concern in health and mental
      health it becomes important to assess the possibilities for application of
      knowledge from this field to improve the quality of life for vulnerable
      populations such as elderly Asian/Pacific Islanders. It is necessary to address
      such aspects of special need as language, life styles, cultural practices, and
      poverty, among others, if preventive measures are to be of value. Recent
      legislation offers some prospect (if not vitiated by reductionist national
      policy) for expanding preventive services to older people who are most in need of
      community services oriented to their special needs. 

PMID- 24276787
TI  - "Get out yesterday and why are you leaving us?" ... a success model of community
      resource development.

PMID- 24276786
TI  - The issue: Should the development and administration of community primary
      prevention be transferred from mental health agencies to education?

PMID- 24276789
TI  - Sphingosine-1-phosphate: a master regulator of lymphocyte egress and immunity.
AB  - Sphingosine-1-phosphate (S1P) is a central factor responsible for lymphocyte
      distribution in the body. S1P is able to control the integrity of various
      effector cell populations within many lymphoid tissues by directing lymphocyte
      egress. In this review, we give an overview of the generation and degradation of
      S1P in specific lymphoid microenvironments. Furthermore, we discuss, sometimes
      contradictory, the functions of the five S1P receptors on different cells in
      diverse tissues and give an idea of additional counteracting chemotactic signals
      for lymphocyte immigration and emigration. We focus special attention to recent
      discoveries of S1P-specific transporters, like spinster-homolog-2 and the active
      secretion of S1P by endothelial cells, erythrocytes and platelets. In addition,
      we describe the microanatomical structures as well as entry and egress routes
      into lymphoid organs which lymphocytes use for efficient trafficking. Finally, we
      give an overview of open questions regarding the regulation of lymphocyte homing
      from primary lymphoid organs to secondary lymphoid organs and back again. 

PMID- 24276788
TI  - The role of glycogen synthase kinase 3-beta in immunity and cell cycle:
      implications in esophageal cancer.
AB  - Esophageal cancer (EC) is one of the most aggressive gastrointestinal
      malignancies, possessing an insidious onset and a poor prognosis. Numerous
      transcription factors and inflammatory mediators have been reported to play a
      pivotal role in the initiation and progression of this cancer. However, the
      specifics of the signaling network responsible for said factors, especially which
      elements are the critical regulators, are still being elucidated. Glycogen
      synthesis kinases 3 (GSK3)beta was originally regarded as a kinase regulating
      glucose metabolism. Accumulating evidence demonstrated that it also played an
      essential role in a variety of cellular processes including proliferation,
      differentiation, inflammation, motility, and survival by regulating various
      transcription factors such as c-Jun, AP-1, beta-catenin, CREB, and NF-kappaB.
      Aberrant regulation of GSK3beta has been shown to promote cell growth in some
      cancers, while suppressing it in others, and thus may play an important role in
      the development of EC. This review will discuss our current understanding of
      GSK3beta signaling, and its control of the expression and activation of various
      transcription factors that mediate the inflammatory response. We will also
      explore some of the known mediators of EC progression, and based on current
      literature, elucidate the potential roles and implications of GSK3 in this
      disease. 

PMID- 24276790
TI  - Nicotinic cholinergic signaling in adipose tissue and pancreatic islets biology:
      revisited function and therapeutic perspectives.
AB  - Nicotinic acetylcholine receptors (nAChRs) are membrane ligand-gated cation
      channels whose activation is triggered by the binding of the endogenous
      neurotransmitter acetylcholine or other biologic compounds including nicotine.
      Their roles in synaptic transmission in the central and peripheral nervous system
      as well as in the neuromuscular junction have been extensively studied. Recent
      implications of nAChRs in intracellular signaling and their detection in
      peripheral nonneural cells (including epithelial cells and immune cells) have
      renewed the interest for this class of ionotropic receptors. In the present
      review, we focus our attention on the potential use of nicotinic cholinergic
      signaling in the treatment of metabolic diseases (such as obesity and diabetes)
      in browsing functions of nAChRs in adipose tissue and pancreatic islet biology.
      In fact, different nAChR subunits can be detected in these metabolic tissues, as
      well as in immune cells interacting with them. Various rodent models of obesity
      and diabetes benefit from stimulation of the nicotinic cholinergic pathway,
      whereas mice deficient for some nAChRs, in particular the alpha7 nAChR subunit,
      harbor a worsened metabolic phenotype. In contrast to potential therapeutic
      applications in metabolic diseases, an overstimulation of this signaling pathway
      during the early stage of development (typically through nicotine exposure during
      fetal life) presents deleterious consequences on ontogeny and functionality of
      adipose tissue and the endocrine pancreas which persist throughout life. 

PMID- 24276791
TI  - Place and sexual partnership transition among young American Indian and Alaska
      native women.
AB  - Multiple challenges expose American Indian and Alaska Native (AIAN) women to high
      risk sexual partnerships and increased risk for HIV/STI. Using a unique sample of
      sexually-active young AIAN women (n = 129), we examined characteristics of last
      three partners and whether transitional partnerships were associated with
      different risk profiles, including where partners met, lived, and had sex.
      Respondents were more likely to have met their previous or current secondary
      partner (P2) at a friend's or family setting (versus work or social setting) (AOR
      = 3.92; 95 % CI 1.31, 11.70). Condom use was less likely when meeting a partner
      at friend's or family settings (AOR = 0.17; 95 % CI 0.05, 0.59). Sexual
      intercourse with P2 (compared to P1) usually took place in "riskier" settings
      such as a car, bar, or outside (AOR = 4.15; 95 % CI 1.59, 10.68). Perceived
      "safe" places, e.g., friend's or family's house, were identified with risky
      behaviors; thus, homogeneous messaging campaigns may promote a false sense of
      safety.

PMID- 24276793
TI  - Structure and organization of two divergent alpha-amylase genes from barley.
AB  - We have isolated several alpha-amylase genomic clones from an Eco RI library of
      barley DNA in lambda-Charon 32. Five of these clones exhibit unique restriction
      maps and differences in their abilities to hybridize with two previously
      characterized alpha-amylase cDNA probes representing two different loci, alpha
      Amy 1 (high pI) and alpha-Amy 2 (low pI) on barley chromosomes 6 and 1,
      respectively. Stringent hybridizations indicate that four of the five genomic
      clones contain alpha-Amy 1 sequences and one contains alpha-Amy 2 sequences. The
      regions containing alpha-amylase genes from one representative genomic clone of
      each group have been sub-cloned, mapped and sequenced. S1-nuclease protection
      experiments indicate that the two alpha-amylase genes contained in these clones
      are functional in aleurone tissue. Transcription start sites in these genes were
      determined by primer extension using specific synthetic oligonucleotide
      primers.The DNA sequences of the two alpha-amylase genes, including promoter
      regions, are divergent, as are the predicted amino acid sequences of the mature
      proteins and the N-terminal "leader" peptides. The alpha-Amy 1 gene contains two
      introns while the alpha-Amy 2 gene has three introns. In the coding region, each
      gene shows 7-10% sequence divergence with respect to the previously characterized
      cDNA clones of the same gene type. Therefore, differences in nucleotide sequences
      can account for some of the isozyme variations seen between the sub-families of
      alpha-amylases and among members of the same subfamily. Although the nucleotide
      sequences of the promoter regions of alpha-Amy 1 and alpha-Amy 2 genes show
      little homology, both contain pairs of inverted repeat elements which could
      constitute regulatory sites. 

PMID- 24276792
TI  - Hepatitis B virus (HBV) infection, immunity and susceptibility among men who have
      sex with men (MSM), Los Angeles County, USA.
AB  - Men who have sex with men (MSM) bear a disproportionate burden of hepatitis B
      virus (HBV) infections. We used serologic data from the National HIV Behavioral
      Surveillance (NHBS) system to determine the prevalence and correlates of HBV
      infection, immunization, and susceptibility in a sample of Los Angeles County
      MSM. Approximately 19 % (95 % CI 15-24 %) had serologic evidence of current or
      past infection, while 35 % (95 % CI 30-40 %) were susceptible. Compared with the
      youngest age group, MSM ages 40-49 years had a lower prevalence of immunization
      (aPR 0.28, 95 % CI 0.17-0.45) and a higher prevalence of infection (aPR 8.53, 95
      % CI 3.95-18.4) and susceptibility (aPR 2.02, 95 % CI 1.13-3.63). We also
      observed poor concordance between self-reported and serologic measures of
      vaccination. Our results indicate the possibility of missed opportunities to
      vaccinate MSM. Gaps in implementing existing vaccination strategies must be
      addressed to increase hepatitis B vaccination coverage for MSM, especially in
      older age groups. 

PMID- 24276794
TI  - Conserved regions in the T-DNA of different Agrobacterium rhizogenes root
      inducing plasmids.
AB  - The T-regions of the three so far identified types of Ri plasmids-corresponding
      to the synthesis of three different hairy root opines, agropine, mannopine and
      cucumopine-have been compared in detail by Southern blot cross hybridizations.
      Two distinct zones of very strong sequence homology, approximately 4 and 3
      kilobases in length respectively, have been identified in all three T-regions.
      The highly conserved sequences, not present in Ti plasmid T-DNA, may encode
      essential rhizogenic functions common to all Agrobacterium rhizogenes T-DNAs. 

PMID- 24276795
TI  - Promoters in the nodulation region of the Rhizobium leguminosarum Sym plasmid
      pRL1JI.
AB  - A region of 16.8 kb of the Sym(biosis) plasmid pRL1JI of Rhizobium leguminosarum,
      consisting of the established 9.7 kb nodulation region which confers nodulation
      ability on Vicia hirsuta and a region of 7.1 kb which appeared to be necessary
      for nodulation on V. sativa and Trifolium subterraneum, was subcloned as
      fragments of maximally 2.5 kb in a newly developed IncQ transcriptional fusion
      vector. The expression of these fragments was studied in Rhizobium. One
      constitutive promoter, pr.nodD, and three plant-exudate inducible promoters were
      found, namely the known pr.nodA and pr.nodF as well as a new promoter designated
      pr.nodM. The latter promoters were localized within 114 bp, 330 bp and 630 bp
      respectively and they regulate the transcription of the operons nodA, B, C, I, J,
      nodF, E and of an operon of at least 2.5 kb located in the 7.1 kb region.
      Induction of the three inducible operons required plant exudate and a functional
      nodD product. The flavanone naringenin could replace plant exudate. Each of the
      three inducible promoters contained a nod-box. A consensus for the nod-box
      sequence, based on known sequences, is proposed. The 114 bp fragment which
      contains pr.nodA activity was used to localize pr.nodA by means of deletion
      mapping. The fragment which appeared necessary for complete pr.nodA activity is
      72 bp in size, contains the complete nod-box and in addition a region of 21 bp
      downstream of the nod-box, in which the loosely conserved sequence AT(T)AG
      appears to be important for promoter activity. 

PMID- 24276796
TI  - A vector for the site-directed, genomic integration of foreign DNA into soybean
      root-nodule bacteria.
AB  - A non-essential DNA region carrying two different repeated sequences (RSbeta3 and
      RSalpha9) adjacent to a nitrogen fixation (nif) gene cluster has been identified
      previously in Bradyrhizobium japonicum strain 110. In closely related B.
      japonicum strains a similar genomic arrangement was found. We constructed a
      mobilizable plasmid vector carrying RSbeta3 and RSalpha9, and a kanamycin
      resistance cassette (nptII gene) plus suitable cloning sites inserted between the
      two repeated sequences. Using this vector (pRJ1035), stable integration of a lacZ
      gene fusion into the B. japonicum genomic RS region was achieved. The resulting
      strain yielded more than 10-fold higher beta-galactosidase activity in soybean
      root nodules as compared to a B. japonicum strain carrying the same lacZ fusion
      on a pRK290-based plasmid. 

PMID- 24276797
TI  - T-DNA rearrangements due to tissue culture: somaclonal variation in crown gall
      tissues.
AB  - After three years of apparent stability in tissue culture, the single cell
      derived shooty crown gall line sNT1.013 produced a revertant shoot which had
      switched from non-rooting (Rod(+)) and octopine synthesizing (Ocs(+)) to Rod(-)
      Ocs(-), indicating that in this revertant TL-DNA genes 4 (causing the Rod(+)
      trait) and gene 3 (causing the Ocs(+) trait) had been inactivated. Southern blots
      revealed that the inactivation of these T-DNA genes was the result of a
      considerable rearrangement of DNA sequences, accompanied by deletions and
      possibly also by DNA amplifications. This study for the first time unambiguously
      proves that foreign genes which have been introduced via Agrobacterium
      tumefaciens can, at a low frequency, be inactivated after T-DNA integration
      because of reorganization of T-DNA sequences during tissue culture. This can be
      considered as an event of somaclonal variation. 

PMID- 24276798
TI  - Paternal inheritance of chloroplast DNA in Larix.
AB  - Restriction enzyme analysis was used to determine the inheritance of chloroplast
      DNA in conifers. The plant material studied included five individual trees of
      European larch (Larix decidua Mill.) and Japanese larch (Larix leptolepis Sieb. &
      Zucc.) and six hybrids from controlled crosses between these species. The
      chloroplast DNA fragment patterns generated by Bam-HI and Bcl-I were species
      specific. Paternal inheritance of chloroplast DNA patterns was found in most
      Larix crosses. One hybrid showed maternal chloroplast DNA patterns. In addition,
      two other hybrids had mixed Bam-HI patterns suggesting recombination between
      maternal and paternal chloroplast DNA. The mechanisms favoring paternal
      inheritance in conifers are not known. Paternal inheritance of chloroplast DNA is
      suggested it to be a general phenomenon in conifers. 

PMID- 24276799
TI  - Nodule-specific glutamine synthetase is expressed before the onset of nitrogen
      fixation in Phaseolus vulgaris L.
AB  - Glutamine synthetase expression was studied in developing root-nodules of common
      bean with regard to the time-course of specific activity, antigen accumulation,
      polypeptide composition and in vitro translation products. This analysis shows
      that the nodule-specific GS polypeptide (GS-gamma) is detected prior to the
      nitrogenase acetylene-reducing activity, and that its accumulation together with
      that of the GS-alpha and GS-beta polypeptides vary with nodule age. GS-gamma is
      present in ineffective nodules, although in a lower ratio to GS-beta than in wild
      type nodules. Comparisons of in vitro translated and in vivo synthesized GS
      polypeptides suggest no post-translational modifications. The possible factors
      and mechanisms involved in the regulation of expression of GS polypeptides are
      discussed. 

PMID- 24276801
TI  - Pre-surgical evaluation for epilepsy surgery.
AB  - Neuropsychological testing may reflect subtle structural changes that may not be
      readily apparent with neuroimaging studies, and physiologic disruption of normal
      neural function secondary to epileptic activity. Neuropsychological testing is
      used during the pre-operative evaluation for epilepsy surgery to assess
      functional brain status, which, in turn, provides important information on the
      risks for post-operative neruopsychological deficits and also provides
      confirmatory evidence of seizure onset laterality in patients whose seizures
      originate in temporal lobes. This review will focus primarily on the pre
      operative neuropsychological of candidates for temporal lobectomy surgery since
      they represent the majority of individuals undergoing ablative epilepsy surgery,
      and also because the literature and knowledge for the neuropsychology of temporal
      lobectomy far exceeds that of any other epilepsy surgical group. 

PMID- 24276800
TI  - Dissociable Response Inhibition in Children With Tourette's Syndrome Compared
      With Children With ADHD.
AB  - OBJECTIVE: This study investigates whether performance in a verbal response task
      (Color-Word Interference Test [CWIT]) and a motor response task (Conners'
      Continuous Performance Test [CCPT]) discriminates children with Tourette's
      Syndrome (TS), ADHD, and typically developing children (TDC). METHOD: Nineteen
      children with TS, 79 with ADHD, and 50 with TDC participated (8-17 years).
      RESULTS: Children with TS committed significantly fewer errors in the verbal
      response task than those with ADHD. Moreover, children with TS but without ADHD
      performed better than TDC. Errors in motor task and speed of response did not
      distinguish between groups. A cautious tendency of response correlated positively
      with rates of tics in children with TS. CONCLUSION: Children with TS were
      superior in inhibiting a prepotent verbal response; however, comorbidity with
      ADHD in those children negatively influenced performance. Results support the
      hypothesis that levels of inhibitory control distinguish children with TS, ADHD,
      and TDC.

PMID- 24276802
TI  - Febrile convulsions in children.
AB  - The term febrile convulsion is not a diagnostic entity. It simply describes any
      seizure that occurs in response to a febrile stimulus. It usually occurs between
      the age of 3 months and 5 years and occurs in 2-4% of young children. The typical
      febrile convulsion is a generalized tonic clonic seizure lasting between a few
      seconds and 15 minutes, followed by a period of drowsiness. Febrile seizures tend
      to occur in families, although the exact mode of inheritance is not known.
      Viruses are the most common cause of illness in children admitted to the hospital
      with a first febrile seizure. Routine laboratory studies are not indicated for
      patients who have febrile seizures and should be performed only as part of the
      evaluation for a source of fever. Prognosis is generally good. Only a small
      minority of children develop epilepsy or recurrent non-febrile seizures. Children
      with febrile seizures are at no greater risk of intellectual impairments than
      their peers. Treatment to prevent recurrence has not been shown to prevent later
      development of epilepsy. 

PMID- 24276803
TI  - Valproate associated acute pancreatitis.
AB  - There is a definitive association between valproate therapy and acute
      pancreatitis. More than 50 cases have been reported. Most of the reported cases
      were mild yet there were a few more cases with higher morbidity and mortality.
      The risk is higher in patients under 20 years of age, during the first year of
      therapy, on the patient having encephalopathy or chronic renal failure and on
      patients with anti-epileptic drug polytherapy. The treatment of pancreatitis is
      supportive, laparotomy should be avoided. Re-challenge is hazardous and should be
      avoided. 

PMID- 24276804
TI  - Clobazam for the treatment of intractable childhood epilepsy.
AB  - OBJECTIVE: Clobazam is a newer 1,5-benzodiazepine used for the treatment of
      epilepsy. It is better tolerated and less sedating than other benzodiazepines. It
      has yet to gain wide use for epilepsy in the Middle East. Our objective is to
      report our experience with clobazam for the treatment of childhood epilepsy.
      METHODS: A cohort of children with intractable epilepsy, defined as recurrent
      seizures after at least 3 anti-epileptic medication trials, were included
      prospectively. Clobazam was added to a maximum dose of 2 mg/kg/day. Follow-up by
      two pediatric neurologists was performed. Therapeutic response was recorded as
      complete (no seizures), good (>50% seizure reduction), fair (<50% seizure
      reduction), or none. RESULTS: Thirty one children (21 males - 10 females), aged 2
      months-15 years (mean 4.6 years) were followed for 3-12 months. Most children
      (68%) had daily seizures and were on multiple anti-epileptic drugs (mean 2.3, +/-
      SD 1). Fourteen (45%) children had Lennox-Gastaut Syndrome. After the
      introduction of clobazam, 11 (35.5%) became completely seizure free and 14 (45%)
      had >50% seizure reduction. Side effects were reported in 7 (22.5%) in the form
      of excessive sedation, vomiting, irritability, behavioral change, and ataxia. In
      4 children these side effects resolved either spontaneously or with dose
      reduction. CONCLUSION: Clobazam is a well tolerated, safe, and very effective
      antiepileptic drug. It has a broad spectrum of antiepileptic activity, minimal
      side effects, and is relatively inexpensive. Wider use of this drug is
      recommended in children with intractable epilepsy.

PMID- 24276805
TI  - Neonatal meningitis.
AB  - OBJECTIVE: To determine the prevalent bacterial agents of neonatal meningitis and
      their antibiotic susceptibility in a referral intensive care unit in Assir
      Central Hospital, Saudi Arabia, during the years 1993-1998. METHODS: Records of
      newborn infants with positive cerebrospinal fluid culture during the period were
      retrospectively studied. RESULTS: There were 1473 nursery admissions, of which 32
      episodes of meningitis occurred amongst 31 neonates. Klebsiella pneumoniae (31%)
      and Serratia marcescens (21%) were the main pathogens. The incidence of
      concurrent septicemia among these infants was 58%. Klebsiella pneumoniae appears
      to dominate in both early and late onset infections. The sex incidence was equal
      and the mortality rate was 48%. CONCLUSION: The survey identifies Klebsiella
      pneumoniae and Serratia sp. as the leading bacterial agents of neonatal
      meningitis in our environment. The relatively high frequency of Serratia
      infection in the present survey appears unique as this organism is comparatively
      rare in other reports across the globe. No Group B Streptococcus was isolated,
      which is in contrast to reports obtained in Europe, America and Australia where
      it is the predominant organism of neonatal sepsis or meningitis. Antibiogram
      identified imipenem and cefotaxime as the empirical antibiotics in infants with a
      clinical diagnosis of neonatal sepsis in our hospital; no more conventional use
      of ampicillin. In view of the changing bacterial pattern of infant infection with
      time even in the same environment, a periodic review of this subject is
      advocated.

PMID- 24276806
TI  - Epidemiological patterns of scoliosis in a spinal unit in Saudi Arabia.
AB  - OBJECTIVE: To study the patterns of scoliosis seen in a major Spinal Unit in
      Saudi Arabia. METHODS: Medical records of 192 Saudi patients with scoliosis seen
      between 1992 and 1997 at the Spinal Unit of the Riyadh Medical Complex (which is
      a major spinal unit in the Kingdom) were studied and analyzed and epidemiological
      data was collected. RESULTS: Fifty nine percent of all cases of scoliosis were
      idiopathic, 7% were secondary to poliomyelitis and 17% were congenital scoliosis.
      The mean age of discovery of idiopathic scoliosis was 12.5 years and at
      presentation was 16 years. The mean Cobb's angle at presentation was 58o.
      Adolescent type constituted 74% of idiopathic curves with a male to female ratio
      of 1:3.8. Thoracic curves were the most common followed by the double major
      curves. Half of the curves were right sided. Infantile idiopathic scoliosis
      constituted 8% with male to female ratio of 4:1 and here left thoracic curves
      formed 50%. The juvenile type constituted the remaining 18% with male to female
      ratio of 1:1.5. CONCLUSION: The pattern of scoliosis in our study is comparable
      in many aspects with other studies carried out elsewhere, with the exception of
      delay in patients age at referral. We believe that our data could reflect a
      possible pattern of the epidemiology of scoliosis in Saudi Arabia, given the fact
      that there is no National Registry. To avoid delay in management, community
      education will help in the early detection of cases.

PMID- 24276807
TI  - Morphologic patterns of male infertility in Saudi patients.
AB  - OBJECTIVE: To determine the predominant histopathological patterns seen in the
      testicular biopsies taken during the investigation of male infertility and to
      compare the obtained histopathological findings with those seen in other similar
      studies. METHODS: This is a retrospective study performed on 230 testicular
      biopsies which were examined in the Department of Pathology at King Khalid
      University Hospital in Riyadh over a period of 10 years. The histopathological
      findings were grouped into 8 different morphologic categories. We have utilized a
      classification that is principally morphologic but that uses known or suspected
      clinical associations in the case of karyotypic abnormalities and excurrent duct
      obstruction. RESULTS: Of the total of 230 testicular biopsies studied, 72 cases
      showed normal spermatogenesis, of which 50 cases were suspected to be associated
      with excurrent duct obstruction. Germinal cell aplasia with and without focal
      spermatogenesis was found in about 90 cases. Thirty cases showed
      hypospermatogenesis, 25 cases showed maturation arrest and 12 cases showed end
      stage tubular sclerosis with interstitial fibrosis. Only one case was noted to
      show features associated with karyotypic abnormalities. CONCLUSION: A higher
      percentage of germinal cell aplasia was noted in this study when compared with
      other similar investigations including one previous local study. Possible causes
      of these discrepancies may be related to several factors including environmental
      effects. The design of the different studies and the criteria used for patient
      selection or both could also explain the cause of these observed differences.

PMID- 24276808
TI  - Sixth nerve palsy and sphenoidal sinusitis.
AB  - Sphenoid sinusitis is an uncommon infection that accounts for approximately 3% of
      all cases of acute sinusitis. It is usually accompanied by pansinusitis; less
      commonly it occurs alone. We are presenting a case of a 30 year old young male
      patient who presented with three weeks history of headache, along with blurry
      vision and diplopia. Neurological examination showed evidence of bilateral sixth
      nerve palsy. Brain magnetic resonance imaging showed evidence of pansinusitis,
      including sphenoidal sinusitis. Cerebrospinal fluid studies showed no evidence of
      meningitis. 

PMID- 24276809
TI  - Munchausen syndrome by proxy.
AB  - Five children (3F:2M), in the age group 1 years to 11 years, with Munchausen
      syndrome by proxy are reported from the Sultanate of Oman. They were seen over a
      four years period from 1996-1999. In all these children, the mother came up with
      history of uncontrolled epilepsy. Carbamazepine was the most common antiepileptic
      drug used. One of these children remained hospitalized elsewhere for nearly 9
      months, as a case of uncontrolled status epilepticus. It took 18 months to 6
      years (mean 2.8 years) to establish the diagnosis and the mother was the offender
      in all. The main lead to diagnosis, was the disparity between history and
      clinical presentation to hospital. The carbamazepine levels were several times
      above the upper limit of therapeutic range. Munchausen syndrome by proxy very
      much exists here, but is possibly less recognized and needs immediate attention
      to formulate policies to identify and manage these children. It is necessary to
      create awareness even in the medical community, to recognise this problem. There
      is an urgent need to develop a child protection council at the national or
      regional level. 

PMID- 24276810
TI  - Neurobrucellosis.
AB  - Brucellosis, which is endemic in Saudi Arabia, can present as a disease with
      multisystem involvement. Occasionally the organisms invade the central nervous
      system producing varied neurological manifestations. Often the clinical diagnosis
      of neurobrucellosis is not straight forward and is obscure. Certain criteria have
      to be fulfilled for the definitive diagnosis of neurobrucellosis. We report 2
      cases of neurobrucellosis which were encountered for the first time during the
      past 10 years at this hospital. 

PMID- 24276811
TI  - Neonatal salmonella meningitis.

PMID- 24276812
TI  - Multiple sclerosis in Syria.

PMID- 24276813
TI  - Statin therapy for primary prevention of cardiovascular disease.
AB  - CLINICAL QUESTION: Do statins reduce rates of cardiovascular events when used for
      primary prevention? BOTTOM LINE: When used for primary prevention, statins are
      associated with lower rates of all-cause mortality, major vascular events, and
      revascularizations compared with placebo. Statin therapy is not associated with
      increased rates of life-threatening adverse effects such as cancer.

PMID- 24276814
TI  - Religion as prose and poetry.

PMID- 24276815
TI  - Belief systems in administration and training.
AB  - Belief systems are instruments for observing events, classifying information,
      communicating with others, and doing therapy. A belief system is a combination of
      feelings, thoughts, actions, and expectations. Belief systems operating in the
      training environment affect how therapists are able to deal with transference and
      countertransference. Belief systems must be evaluated in terms of whether they
      are comprehensive, delusional, absent, sinelusional, and the extent to which they
      are structuring us. The use of belief systems provides us with an appreciation of
      our own activities, an instrument for conveying our feelings, and, most
      importantly, a means for understanding the views of others. 

PMID- 24276816
TI  - Compassion without illusion.
AB  - This paper describes the present crisis in the mental health system relative to
      the chronically mentally ill. It asks how we can apply our usual social contract
      with the sick to noncompliant mental patients. The paper identifies some American
      assumptions about freedom and individualism that undermine a more effective
      response and offers alternative assumptions based on the Judeo-Christian
      tradition that may help resolve some difficulties. 

PMID- 24276817
TI  - Pilgrimage and enlightenment.
AB  - This essay explores the ideas of pilgrimage and some of the pilgrim-images in
      human life. It also explores the images of light and enlightenment as they
      pertain to the pilgrimage experience, suggesting that enlightenment, in a
      religious sense, is an act of surrender instead of will. 

PMID- 24276819
TI  - A comparison of alcohol drinkers at a state and private university.
AB  - The purpose of this study was to compare the drinking behaviors of college
      students at a large state university to the drinking behaviors of their
      counterparts at a smaller church university.Questionnaires were administered to a
      total sample of 764-434 students represented the state university, while 330
      students represented the church university. Statistical analysis of the data
      revealed significant differences at the .05 alpha level between the two groups of
      drinkers. However, many similarities between the two groups did exist. Two of the
      three null hypotheses were supported by the data. Only in one category did the
      drinkers at the church school respond notably higher than the state school
      drinkers. Considerably more church school drinkers admitted to drinking primarily
      when in a lonely or sad mood than the state school drinkers. Drinkers at the
      church school felt a need to hide or be alone when drinking and did not use
      alcohol to socialize as often as their state school counterparts. 

PMID- 24276818
TI  - Occupational choices of daughters of practicing rabbis.
AB  - This paper examines the psychological impact that rabbis, as character types,
      have on their daughters. It describes how the father's impact psychologically
      predisposes these women to enter the helping professions in disporportionate
      numbers, and it shows how these job choices are often a means of coping with
      psychological issues connected to their upbringing. 

PMID- 24276820
TI  - Learning through symbol, myth, model, and ritual.
AB  - An interdisciplinary course entitled "Religious and Spiritual Issues in Health
      Care" was offered for nursing students, medical students, and seminary students.
      The course was designed to explore religious responses to human suffering and to
      examine the role of different health care professionals with regard to spiritual
      concerns of patients.The identification of symbol, the retelling of myth, the
      presentation of model, and the enactment of ritual enhanced the learning process.
      In the context of the universality of human suffering, professional differences
      were recognized and respected.Teamwork in health care is a process which can be
      learned cognitively and affectively by affirming and sharing professional values
      with other health care professions. 

PMID- 24276821
TI  - The modulation of the conversion of l-aminocyclopropane-l-carboxylic acid to
      ethylene by light.
AB  - Endogenous ethylene production of tobacco leaves was similar in light and in
      darkness. However, the rate of conversion of exogenously applied l
      aminocyclopropane-l-carboxylic acid (ACC) to ethylene was reversibly inhibited by
      light. Virus-stimulated ethylene production, during the hypersensitive reaction
      of tobacco leaves to tobacco mosaic virus, was likewise inhibited by light. Under
      such circumstances ethylene production is limited at the level of the conversion
      of ACC to ethylene. Inhibition of the increase in ACC-stimulated ethylene
      production by cycloheximide and 2-(4-methyl-2,6-dinitroanilino)-N-methyl
      propionamide after shifting leaf discs from light to darkness indicated that de
      novo protein synthsis was involved. Regulation of ACC-dependent ethylene
      production by reversible oxidation/reduction of essential SH groups, as suggested
      by Gepstein and Thimann (1980, Planta 149, 196-199) could be excluded. Instead,
      regulation of the ACC-converting enzyme at the level of both
      synthesis/degradation and activation/inactivation is suggested. Phytochrome was
      not involved in light inhibition, but low intensities of either red or blue light
      decreased the rate of ACC conversion. Dichlorophenyldimethylurea counteracted the
      inhibitory effect of light, indicating that (part of) the photosynthetic system
      is involved in the light inhibition. The ethylene production of Pharbitis
      cotyledons grown in darkness or light, either in the presence of absence of the
      inhibitor of carotenoid synthesis, SAN 9789 (norflurazon), supported this view. 

PMID- 24276822
TI  - The role of glycosylation in storage-protein synthesis in developing pea seeds.
AB  - Intact pea (Pisum sativum L.) cotyledons were incubated with [(14)C]glucosamine
      at several stages of seed development and the resultant radioactive proteins were
      analysed by gel electrophoresis combined with immunoaffinity chromatography and
      sucrose gradient fractionation. Glucosamine was incorporated into at least five
      vicilin polypeptides (approx. molecular weight 70,000; 50,000, two components;
      14,000, two components). No incorporation was detected into the subunits of
      legumin. Tunicamycin at 50 MUg/ml largely inhibited glucosamine incorporation but
      had little effect on the incorporation of (14)C-labelled amino acids into
      cotyledon proteins, including vicilin. The assembly of vicilin polypeptides into
      full-sized protein oligomers (7-9 S) was also unaffected by tunicamycin.
      Chromatography on concanavalin A confirmed that glycosylation of cotyledon
      proteins was inhibited by tunicamycin. It is concluded that glycosylation of most
      cotyledonary proteins involves lipid-linked sugar intermediates, but that
      glycosylation itself is not an essential step in the synthesis of vicilin
      polypeptides nor in their assembly into oligomers. 

PMID- 24276823
TI  - The intracellular pH of isolated, photosynthetically active Asparagus mesophyll
      cells.
AB  - The intracellular pH of isolated, photosynthetically active mesophyll cells of
      Asparagus sprengeri Regel has been determined, in the light and dark, by the
      distribution of the weak acid 5,5-dimethyl-[2-(14)C]oxazolidine-2,4-dione
      ([(14)C]DMO) between the cells and the liquid medium. [(14)C]DMO was taken up
      rapidly, reaching equilibrium in 7-10 min of incubation, but was not metabolized
      by the cells, and intracellular binding of the compound was minimal. The
      intracellular pH, measured at saturating light fluence and 1.5 mM sodium
      bicarbonate, was found to remain relatively constant at 6.95-7.21 over the
      external pH range of 5.5-7.2. Illumination of the cells increased the
      intracellular pH compared to dark controls. The pH of the cytoplasm, excluding
      and including the chloroplasts ("cytoplasmic" and "bulk cytoplasmic",
      respectively) was calculated from the experimentally derived intracellular
      [(14)C]DMO concentration and estimates of the vacuolar, chloroplastic and
      cytoplasmic volumes. The calculated cytoplasmic pH was similar in the light and
      dark, being 7.75 and 7.74, respectively, while the calculated pH of bulk
      cytoplasm was 7.85 in the light and 7.49 in the dark. Theoretical analysis
      indicated that intracellular pH is a good indicator of changes in the bulk
      cytoplasmic pH but insensitive to changes in vacuolar pH. The external pH optimum
      for photosynthesis (O2 evolution) of isolated Asparagus cells was pH 7.2. At pH
      8.0 photosynthesis was inhibited by 30% and at pH 5.25 by 45%. Inhibition at
      alkaline pH may be the result of a decrease in the pH gradient between the cells
      and the medium, causing CO2 limitation in the cell. At acid pH, decrease in
      internal pH caused by substantial accumulation of inorganic carbon may account
      for the loss in photosynthetic activity. 

PMID- 24276824
TI  - Inhibition by silver ions of gas space (aerenchyma) formation in adventitious
      roots of Zea mays L. subjected to exogenous ethylene or to oxygen deficiency.
AB  - We have studied the role of ethylene in accelerating the lytic formation of gas
      spaces (aerenchyma) in the cortex of adventitious roots of maize (Zea mays L.)
      growing in poorly aerated conditions. Such roots had previously been shown to
      contain increased concentrations of ethylene. Ten day-old maize plants bearing
      seminal roots and one whorl of emerging adventitious roots were grown in nutrient
      solution bubbled with air, ethylene in air (0.1 to 5.0 MUl l(-1)), or allowed to
      become oxygen-deficient in nonaerated (but not completely anaerobic) solution.
      Additions of 0.1 MUl l(-1) ethylene or more promoted the formation of aerenchyma,
      with lysis of up to 47% of the cortical cells. The effects of non-aeration were
      similar to those of exogenous ethylene. When silver ions, an ethylene antagonist,
      were present at low, non-toxic concentrations (circa 0.6 MUM), aerenchyma
      formation was prevented in ethylene treated roots and in those exposed to oxygen
      deficiency. Silver ions also blocked the inhibiting effect of exogenous ethylene
      on root extension. By contrast, the suppression of aerenchyma formation by silver
      ions under oxygendeficient conditions was associated with a retardation of root
      extension, indicating the importance of aerenchyma for root growth in poorly
      aerated media. Rates of production of ethylene by excised roots were stimulated
      by a previous non-aeration treatment. The effectiveness of Ag(+) in inhibiting
      equally the action on cortical cells of exogenous ethylene and of non-aeration,
      supports the view that gas space (aerenchyma) formation in adventitious roots
      'adpted' to oxygendeficient environments is mediated by increased concentrations
      of endogenous ethylene. The possibility that extra ethylene could arise from
      increased biosynthesis of a precursor in root tissues with a restricted oxygen
      supply is discussed. 

PMID- 24276825
TI  - Metabolism and decarboxylation of glycollate and serine in leaf peroxisomes.
AB  - The linked utilization of glycollate and L-serine has been studied in peroxisomal
      preparations from leaves of spinach beet (Beta vulgaris L.). The generation of
      glycine from glycollate was found to be balanced by the production of
      hydroxypyruvate from serine and similarly by 2-oxoglutarate when L-glutamate was
      substituted for L-serine. In the presence of L-malate and catalytic quantities of
      NAD(+), about 40% of the hydroxypyruvate was converted further to glycerate,
      whereas with substrate quantities of NADH, this conversion was almost
      quantitative. CO2 was released from the carboxyl groups of both glycollate and
      serine. Since the decarboxylation of both substrates was greatly in creased by
      the catalase inhibitor, 3-amino-1,2,4-triazole, and abolished by bovine liver
      catalase, it was attributed to the nonenzymic attack of H2O2, generated in
      glycollate oxidation, upon glyoxylate and hydroxypyruvate respectively. At 25-30
      degrees  C, about 10% of the glyoxylate and hydroxypyruvate accumulated was
      decarboxylated, and the release of CO2 from each keto-acid was related to the
      amounts present. It is suggested that hydroxypyruvate decarboxylation might
      contribute significantly to photorespiration and provide a metabolic route for
      the complete oxidation of glycollate, the magnitude of this contribution
      depending upon the concentrations of glyoxylate and hydroxypyruvate in the
      peroxisomes. 

PMID- 24276826
TI  - Glutamate and serine as competing donors for amination of glyoxylate in leaf
      peroxisomes.
AB  - When provided with glycollate, peroxisomal extracts of leaves of spinach beet
      (Beta vulgaris L. cv.) converted L-serine and L-glutamate to hydroxypyruvate and
      2-oxoglutarate respectively. When approximately saturating concentrations of each
      of these amino acids were incubated separately with glycollate, the utilization
      of serine was greater than that of glutamate. The utilization of glutamate was
      substantially reduced by the presence of relatively low concentrations of serine
      in the reaction mixture, whereas even high concentrations of glutamate caused
      only small reductions in serine utilization. Over the entire range of
      concentrations of amino acids examined, serine was invariably the preferred amino
      group donor, but this preference was abolished at higher concentrations of
      glyoxylate. Serine not only competed favourably for glyoxylate but also inhibited
      L-glutamate: glyoxylate aminotransferase (GGAT), the degree of inhibition
      depending upon the glyoxylate concentration. Studies of L-serine: glyoxylate
      aminotransferase (SGAT) and GGAT in partially purified extracts from spinach-beet
      leaves confirmed that serine competitively inhibited GGAT but glutamate did not
      affect SGAT. Both enzymes were inhibited by high glyoxylate concentrations, the
      inhibition being relieved by suitably high concentrations of the appropriate
      amino acid. It is concluded that at the low glyoxylate concentrations likely to
      occur in vivo, the preferential utilization of serine would ensure flux through
      the glycollate pathway to glycerate, but at higher concentrations of glyoxylate,
      both enzymes could be fully active in glyoxylate amination. 

PMID- 24276827
TI  - Stomatal responses in isolated epidermis of the crassulacean acid metabolism
      plant Kalanchoe daigremontiana Hamet et Perr.
AB  - The optimal conditions for opening of stomata in detached epidermis of the
      Crassulacean Acid Metabolism (CAM) plant Kalanchoe daigremontiana were
      determined. Stomatal opening in CO2-free air was unaffected by light so
      subsequently all epidermal strips were incubated in the dark and in CO2-free air.
      Apertures were maximal after 3 h incubation and were significantly greater at 15
      degrees  C than 25 degrees  C. Thus stomata in isolated epidermis of this species
      can respond directly to temperature. Stomatal opening was greatest when the
      incubating buffer contained 17.6 mol m(-3) K(+), but decreased linearly with
      increasing K(+) concentrations between 17.6 and 300 mol m(-3); the decrease in
      aperture was shown to be associated with increasing osmotic potentials of the
      solutions. Reasons for this behaviour, which differs from that of many C3 and C4
      species, are discussed. Stomatal apertures declined linearly upon incubation of
      epidermis on buffer solutions containing between 10(-11) and 10(-5) mol m(-3)
      abscisic acid (ABA). Hence stomata on isolated epidermis of K. daigremontiana
      respond to lower concentrations of ABA than those of any species reported
      previously. 

PMID- 24276828
TI  - Structural homology of storage proteins coded by the Hor-1 locus of barley
      (Hordeum vulgare L.).
AB  - Three 'C' hordein fractions were prepared by ion-exchange chromatography of a
      total hordein preparation on carboxymethyl cellulose at pH 4.6 Polyacrylamide gel
      electrophoresis at pH 3.2 and sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) at pH 8.9 showed that each fraction contained a single
      major band. The apparent molecular weights of these were determined by SDS-PAGE
      as 58, 57, and 54,000. When compared by isoelectric focusing, however, the 58 and
      57,000 components each separated into two major bands and the 54,000 component
      into four. Amino acid analysis showed that although the three fractions had
      similar compositions with high glutamate+glutamine (38-39%), proline (30-32%) and
      phenylalanine (8-9%) contents, some differences were present, notably in the
      relative content of lysine. The three fractions had identical amino acid
      sequences for the first ten residues at the N-terminal end. They also had
      identical sequences for the first five residues at the C-terminal end, with the
      exception that a mixture of two amino acids were released from position 4 of the
      58,000 fraction only. Peptide mapping with three enzymes (trypsin, chymotrypsin
      and V8 protease) indicated that the 58 and 57,000 fractions were more closely
      related to each other than to the 54,000 fraction. It is suggested that the 57
      and 58,000 fractions and the 54,000 fraction constitute two families of closely
      related polypeptides which are coded by genes derived from the duplication and
      divergence of a single ancestral gene. 

PMID- 24276829
TI  - Occurrence of xanthine dehydrogenase in Chlamydomonas reinhardii: A common
      cofactor shared by xanthine dehydrogenase and nitrate reductase.
AB  - Wild-type Chlamydomonas reinhardii cells have xanthine dehydrogenase activity
      when grown with nitrate, nitrite, urea, or amino acid media. Mutant strains 102,
      104, and 307 of Chlamydomonas, lacking both xanthine dehydrogenase and nitrate
      reductase activities, were incapable of restoring the NADPH-nitrate reductase
      activity of the mutant nit-1 of Neurospora crassa, whereas wild type cells and
      mutants 203 and 305 had xanthine dehydrogenase and were able to reconstitute the
      nitrate reductase activity of nit-1 of Neurospora. Therefore, it is concluded
      that in Chlamydomonas a common cofactor is shared by xanthine dehydrogenase and
      nitrate reductase. Xanthine dehydrogenase is repressed by ammonia and seems to be
      inessential for growth of Chlamydomonas. 

PMID- 24276830
TI  - A comparative study of the responsivity of Sinapis alba L. seedlings to pulsed
      and continuous irradiation.
AB  - Anthocyanin formation in 36h dark grown Sinapis alba L. seedlings and inhibition
      of hypocotyl elongation in 36h and 54h dark grown and 54h and 7 day light grown
      seedlings in response to continuous red light could be substituted for by hourly
      5 min light pulses where the total fluence over the irradiation period is the
      same. These pulses are partially (36h) or almost totally (54h and 7 day)
      reversible by subsequent far-red (RG 9) light pulses. In contrast to 654 nm
      light, hourly light pulses with 552 nm, 449 nm and 715 nm can at best only
      partially substitute for continuous irradiation. These data are discussed with
      respect to the commonly used models for the phytochrome high irradiance response.

PMID- 24276831
TI  - Direct differentiation of tracheary elements in cultured explants of gamma
      irradiated tubers of Helianthus tuberosus.
AB  - Exposure of Jerusalem artichoke (Helianthus tuberosus) tubers to 20 krad doses of
      gamma-irradiation inhibits mitosis and DNA synthesis in cultures subsequently
      inititated from such material. When cultures were initiated from immature,
      developing tubers, tracheary elements differentiated from parenchyma cells in
      response to auxin in the culture medium. The capacity for direct differentiation
      in irradiated tissues declined with tuber maturity, and in fully mature tubers
      xylem differentiation only occurred in non-irradiated controls, following a
      period of cell division. An hypothesis concerning changes in developmental
      plasticity of cells in relation to the cell cycle is discussed. 

PMID- 24276832
TI  - Action spectra for changes in the "high irradiance reaction" in hypocotyls of
      Sinapis alba L.
AB  - Detailed action spectra are presented for the inhibition of hypocotyl extension
      in dark-grown Sinapis alba L. seedlings by continuous (24 h) narrow waveband
      monochromatic light between 336 nm and 783 nm. The results show four distinct
      wavebands of major inhibitory action; these are centred in the ultra-violet
      (lambdamax=367 nm), blue (lambdamax=446 nm), red (lambdamax=653 nm) and far-red
      (lambdamax=712 nm) wavebands. Previous irradiation of the plants with red light
      (which also decreases Ptot) causes decreased inhibitory action by all wavelengths
      except those responsible for the red light inhibitory response. Pre-irradiation
      did not alter the wavelength of the action maxima. It is concluded that ultra
      violet and blue light act mainly on a photoreceptor which is different from
      phytochrome. 

PMID- 24276833
TI  - Secondary fluorescence kinetics of spinach leaves in relation to the onset of
      photosynthetic carbon assimilation.
AB  - When spinach leaves are re-illuminated, after dark periods of 90 s or less, an
      initial fluorescence peak is observed which rapidly gives way to a much lower
      terminal value. After 2 min or more in the dark, however, there is a secondary
      rise, at about 50-70 s, which then gives way, more slowly, to approximately the
      same low terminal value as before. The secondary rise is eliminated or disguised
      by feeding D,L-glyceraldehyde (a specific inhibitor of photosynthetic carbon
      assimilation) and by manose, 2-deoxyglucose and glucosamine, all of which are
      believed to sequester cytoplasmic orthophosphate. This secondary rise in
      fluorescence is discussed in relation to photosynthetic induction and the manner
      in which these compounds may modulate fluorescence by their effect on the
      availability of orthophosphate and their consequent impact on the adenylate
      status of the stroma. 

PMID- 24276834
TI  - Ribulose 1,5-bisphosphate carboxylase and polyhedral bodies of Chlorogloeopsis
      fritschii.
AB  - Ribulose 1,5-bisphosphate (RuBP) carboxylase (EC 4.1.1.39) activity was
      approximately equally distributed between supernatant and pellet fractions
      produced by differential centrifugation of disrupted cells of Chlorogloeopsis
      fritschii. Low ionic strength buffer favoured the recovery of particulate RuBP
      carboxylase. Density gradient centrifugation of resuspended cell-free particulate
      material produced a single band of RuBP carboxylase activity, which was
      associated with the polyhedral body fraction, rather than with the thylakoids or
      other observable particles. Isolated polyhedral body stability was improved by
      density gradient centrifugation through gradients of Percoll plus sucrose in
      buffer, which yielded apparently intact polyhedral bodies. These were 100 to 150
      nm in diameter and contained ring-shaped, 12 nm diameter particles. It is
      inferred that the C. fritschii polyhedral bodies are carboxysomes. Sodium dodecyl
      sulphate (SDS) polyacrylamide gel electrophoresis of SDS-dissociated polyhedral
      bodies revealed 8 major polypeptides. The most abundant, with molecular weights
      of 52,000 and 13,000, correspond with the large and small subunits, respectively,
      of RuBP carboxylase. 

PMID- 24276835
TI  - Features and outcomes of patients who underwent cardiac device deactivation.
AB  - IMPORTANCE: Little is known about patients who undergo cardiovascular implantable
      electronic device deactivation. OBJECTIVE: To describe features and outcomes of
      patients who underwent cardiovascular implantable electronic device deactivation.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of medical records of 150
      patients at a tertiary academic medical center (Mayo Clinic, Rochester,
      Minnesota). EXPOSURE Cardiovascular implantable electronic device deactivation.
      MAIN OUTCOMES AND MEASURES: Demographic and clinical data and information
      regarding advance directives, ethics consultations, palliative medicine
      consultations, and cardiovascular implantable electronic device deactivations.
      RESULTS: Of the 150 patients (median age, 79 years; 67% were male), 149 (99%) had
      poor or terminal prognoses. Overall, 118 patients (79%) underwent deactivation of
      tachycardia therapies only, and 32 (21%) underwent deactivation of bradycardia
      therapies with or without tachycardia therapies (6 patients [4%] were pacemaker
      dependent). Half of the deactivation requests (51%) were made by surrogates. A
      majority of deactivations (55%) were carried out by nurses. Although 85 patients
      (57%) had advance directives, only 1 mentioned the device in the directive.
      Ethics consultations occurred in 3 patients (2%) and palliative medicine
      consultations in 64 (43%). The proportions of patients who died within 1 month of
      device deactivation were similar for those who underwent deactivation of
      tachycardia therapies only and those who underwent deactivation of bradycardia
      therapies with or without tachycardia therapies (85% vs 94%; P = .37).
      CONCLUSIONS AND RELEVANCE: Most requests for cardiovascular implantable
      electronic device deactivation were for implantable cardioverter-defibrillator
      delivered tachycardia therapies only. Many of these requests were made by
      surrogates. Advance directives executed by patients with these devices rarely
      addressed device management. Regardless of device therapy, most patients died
      shortly after device deactivation. Hence, a device deactivation decision may
      reflect the seriousness of a given patient's underlying illness. Patients with
      devices should engage in advance care planning to ensure that future care is
      consistent with their preferences.

PMID- 24276836
TI  - Triplex-mediated analysis of cytosine methylation at CpA sites in DNA.
AB  - Modified triplex-forming oligonucleotides distinguish 5-methyl cytosine from
      unmethylated cytosine in DNA duplexes by differences in triplex melting
      temperatures. The discrimination is sequence-specific; dramatic differences in
      stabilisation are seen for CpA methylation, whereas CpG methylation is not
      detected. This direct detection of DNA methylation constitutes a new approach for
      epigenetic analysis. 

PMID- 24276837
TI  - Malignant paraganglioma presenting with hemorrhagic stroke in a child.
AB  - Sympathetic paragangliomas are rare catecholamine-secreting tumors of extra
      adrenal origin, and their diagnosis in children is even more infrequent. They
      usually manifest as hypertension, palpitations, headache, sweating, and pallor.
      Malignant paragangliomas are identified by the presence of metastasis.
      Hemorrhagic stroke in the pediatric population is a life-threatening condition
      with several etiologies. We report here the case of a 12-year-old boy with
      malignant sympathetic paraganglioma presenting with hemorrhagic stroke. Severe
      hypertension was found and the patient evolved into a coma. Brain computed
      tomography scan showed right thalamus hemorrhage with intraventricular extension.
      After clinical improvement, further investigation revealed elevated catecholamine
      and metanephrine levels, and 2 abdominal tumors were identified by computed
      tomography. Resection of both lesions was performed, and histologic findings were
      consistent with paraganglioma. Multiple metastatic involvement of bones and soft
      tissues appeared several years later. Genetic testing identified a mutation in
      succinate dehydrogenase subunit B gene, with paternal transmission. 131I
      metaiodobenzylguanidine therapy was performed 3 times with no tumoral response.
      Our patient is alive, with adequate quality of life, 25 years after initial
      diagnosis. To our knowledge, this is the first pediatric case of paraganglioma
      presenting with hemorrhagic stroke. Intracerebral hemorrhage was probably caused
      by severe hypertension due to paraganglioma. Therefore, we expand the recognized
      clinical spectrum of the disease. Physicians evaluating children with hemorrhagic
      stroke, particularly if hypertension is a main symptom, should consider the
      possibility of catecholamine-secreting tumors. Metastatic disease is associated
      with succinate dehydrogenase subunit B mutations and, although some patients have
      poor prognosis, progression can be indolent.

PMID- 24276838
TI  - Intravenous magnesium sulfate for vaso-occlusive episodes in sickle cell disease.
AB  - BACKGROUND AND OBJECTIVE: Vaso-occlusive episodes (VOEs) are the most common
      complication of sickle cell disease in children. Treatment with magnesium seems
      to improve cellular hydration and may result in reduced vaso-occlusion. This
      study aimed to determine if intravenous (IV) magnesium sulfate (MgSO4) reduces
      length of stay (LOS) in hospital, pain scores, and cumulative analgesia when
      compared with placebo. METHODS: Randomized, double-blind, placebo-controlled
      trial in children aged 4 to 18 years requiring admission to hospital with a
      sickle cell disease VOE requiring IV analgesia. Participating children received
      IV MgSO4 (100 mg/kg) every 8 hours or placebo in addition to standard therapy. We
      used a t test or Mann-Whitney test (continuous variables), Fisher's exact test,
      or chi2 test (frequencies). P values were considered significant if <.05, and 95%
      confidence intervals were calculated for the difference between groups. RESULTS:
      One hundred six children were randomly assigned to the study, and 104 were
      included. Fifty-one (49%) received MgSO4. Children's mean age was 12.4 years
      (range: 4-18 years; SD: 3.8 years), and 56 (54%) were females. There was no
      significant difference in the primary outcome measure, LOS in hospital, with a
      mean of 132.6 and 117.7 hours in the MgSO4 and placebo groups, respectively (P =
      .41). There was no significant difference between groups for the secondary
      outcomes of mean pain scores (4.9 +/- 2.6 vs 4.8 +/- 2.6, respectively; P = .92)
      or analgesic requirements (continuous morphine infusion [P = .928], boluses of IV
      morphine [P = .82], acetaminophen [P = .34], ibuprofen [P = .15], naproxen [P =
      .10]). Only minor adverse events were recorded in both groups. Pain at the
      infusion site was more common in the MgSO4 group. CONCLUSIONS: IV MgSO4 was well
      tolerated but had no effect on the LOS in hospital, pain scores, or cumulative
      analgesia use in admitted children with a VOE.

PMID- 24276839
TI  - Community household income and resource utilization for common inpatient
      pediatric conditions.
AB  - BACKGROUND AND OBJECTIVE: Child health is influenced by biomedical and
      socioeconomic factors. Few studies have explored the relationship between
      community-level income and inpatient resource utilization for children. Our
      objective was to analyze inpatient costs for children hospitalized with common
      conditions in relation to zip code-based median annual household income (HHI).
      METHODS: Retrospective national cohort from 32 freestanding children's hospitals
      for asthma, diabetes, bronchiolitis and respiratory syncytial virus, pneumonia,
      and kidney and urinary tract infections. Standardized cost of care for individual
      hospitalizations and across hospitalizations for the same patient and condition
      were modeled by using mixed-effects methods, adjusting for severity of illness,
      age, gender, and race. Main exposure was median annual HHI. Posthoc tests
      compared adjusted standardized costs for patients from the lowest and highest
      income groups. RESULTS: From 116,636 hospitalizations, 4 of 5 conditions had
      differences at the hospitalization and at the patient level, with lowest-income
      groups having higher costs. The individual hospitalization level cost differences
      ranged from $187 (4.1%) to $404 (6.4%). Patient-level cost differences ranged
      from $310 to $1087 or 6.5% to 15% higher for the lowest-income patients. Higher
      costs were typically not for laboratory, imaging, or pharmacy costs. In total,
      patients from lowest income zip codes had $8.4 million more in hospitalization
      level costs and $13.6 million more in patient-level costs. CONCLUSIONS: Lower
      community-level HHI is associated with higher inpatient costs of care for 4 of 5
      common pediatric conditions. These findings highlight the need to consider
      socioeconomic status in health care system design, delivery, and reimbursement
      calculations.

PMID- 24276841
TI  - The political history of PKU: reflections on 50 years of newborn screening.

PMID- 24276840
TI  - Adiposity and different types of screen time.
AB  - OBJECTIVE: Few prospective studies have examined separate forms of screen time in
      relation to adiposity. Our objective was to assess independent relations of
      television, electronic games (video/computer), and digital versatile disc
      (DVD)/videos and total screen time with change in adolescent BMI. METHODS: Using
      data from the 2004, 2006, and 2008 waves of the ongoing Growing up Today Study
      II, we assessed baseline and 2-year change in reported screen time in relation to
      concurrent change in BMI among 4287 girls and 3505 boys aged 9 to 16 years in
      2004. Gender-specific models adjusted for previous BMI, age, race/ethnicity,
      growth/development, months between questionnaires, and physical activity.
      RESULTS: Among girls and boys, each hour per day increase in reported television
      viewing was associated with a 0.09 increase in BMI (Ps < .001), and each hour per
      day increase in total screen time was associated with a 0.07 increase among girls
      and 0.05 increase among boys (Ps < .001). Among girls only, greater baseline
      television, games, and total screen time and change in DVDs/videos were
      associated with gains in BMI (Ps < .05). BMI gains associated with change in
      television and total screen time were stronger among overweight girls than lean
      girls (Ps-heterogeneity < .001). CONCLUSIONS: Television, which remains the
      steadiest source of food advertising, was most consistently associated with BMI
      gains. Among girls, electronic games and DVDs/videos were also related to
      increased BMI, possibly due to influences of product placements and advergames on
      diet and/or distracted eating. Adolescents, especially overweight adolescents,
      may benefit from reduced time with multiple types of media.

PMID- 24276842
TI  - National, regional, and state abusive head trauma: application of the CDC
      algorithm.
AB  - OBJECTIVE: To examine national, regional, and state abusive head trauma (AHT)
      trends using child hospital discharge data by applying a new coding algorithm
      developed by the Centers for Disease Control and Prevention (CDC). METHODS: Data
      from 4 waves of the Kids' Inpatient Database and annual discharge data from North
      Carolina were used to determine trends in AHT incidence among children <1 year of
      age between 2000 and 2009. National, regional, and state incidence rates were
      calculated. Poisson regression analyses were used to examine national, regional,
      and state AHT trends. RESULTS: The CDC narrow and broad algorithms identified
      5437 and 6317 cases, respectively, in the 4 years of KID weighted data. This
      yielded average annual incidences of 33.4 and 38.8 cases per 100,000 children <1
      year of age. There was no statistically significant change in national rates.
      There were variations by region of the country, with significantly different
      trends in the Midwest and West. State data for North Carolina showed wide annual
      variation in rates, with no significant trend. CONCLUSIONS: The new coding
      algorithm resulted in the highest AHT rates reported to date. At the same time,
      we found large but statistically insignificant annual variations in AHT rates in
      1 large state. This suggests that caution should be used in interpreting AHT
      trends and attributing changes in rates as being caused by changes in policies,
      programs, or the economy.

PMID- 24276843
TI  - Incidence of obesity among young U.S. children living in low-income families,
      2008-2011.
AB  - OBJECTIVE: To examine the incidence and reverse of obesity among young low-income
      children and variations across population subgroups. METHODS: We included 1.2
      million participants in federally funded child health and nutrition programs who
      were 0 to 23 months old in 2008 and were followed up 24 to 35 months later in
      2010-2011. Weight and height were measured. Obesity at baseline was defined as
      gender-specific weight-for-length >=95th percentile on the 2000 Centers for
      Disease Control and Prevention growth charts. Obesity at follow-up was defined as
      gender-specific BMI-for-age >=95th percentile. We used a multivariable log
      binomial model to estimate relative risk of obesity adjusting for gender,
      baseline age, race/ethnicity, duration of follow-up, and baseline weight-for
      length percentile. RESULTS: The incidence of obesity was 11.0% after the follow
      up period. The incidence was significantly higher among boys versus girls and
      higher among children aged 0 to 11 months at baseline versus those older.
      Compared with non-Hispanic whites, the risk of obesity was 35% higher among
      Hispanics and 49% higher among American Indians (AIs)/Alaska Natives (ANs), but
      8% lower among non-Hispanic African Americans. Among children who were obese at
      baseline, 36.5% remained obese and 63.5% were nonobese at follow-up. The
      proportion of reversing of obesity was significantly lower among Hispanics and
      AIs/ANs than that among other racial/ethnic groups. CONCLUSIONS: The high
      incidence underscores the importance of early-life obesity prevention in multiple
      settings for low-income children and their families. The variations within
      population subgroups suggest that culturally appropriate intervention efforts
      should be focused on Hispanics and AIs/ANs.

PMID- 24276844
TI  - Telemedicine consultations and medication errors in rural emergency departments.
AB  - OBJECTIVE: To compare the frequency of physician-related medication errors among
      seriously ill and injured children receiving telemedicine consultations, similar
      children receiving telephone consultations, and similar children receiving no
      consultations in rural emergency departments (EDs). METHODS: We conducted
      retrospective chart reviews on seriously ill and injured children presenting to 8
      rural EDs with access to pediatric critical care physicians from an academic
      children's hospital. Physician-related ED medication errors were independently
      identified by 2 pediatric pharmacists by using a previously published instrument.
      The unit of analysis was medication administered. The association of telemedicine
      consultations with ED medication errors was modeled by using hierarchical
      logistic regression adjusting for covariates (age, risk of admission, year of
      consultation, and hospital) and clustering at the patient level. RESULTS: Among
      the 234 patients in the study, 73 received telemedicine consultations, 85
      received telephone consultations, and 76 received no specialist consultations.
      Medications for patients who received telemedicine consultations had
      significantly fewer physician-related errors than medications for patients who
      received telephone consultations or no consultations (3.4% vs. 10.8% and 12.5%,
      respectively; P < .05). In hierarchical logistic regression analysis, medications
      for patients who received telemedicine consultations had a lower odds of
      physician-related errors than medications for patients who received telephone
      consultations (odds ratio: 0.19, P < .05) or no consultations (odds ratio: 0.13,
      P < .05). CONCLUSIONS: Pediatric critical care telemedicine consultations were
      associated with a significantly reduced risk of physician-related ED medication
      errors among seriously ill and injured children in rural EDs.

PMID- 24276845
TI  - Bidirectional associations between mothers' and fathers' parenting consistency
      and child BMI.
AB  - BACKGROUND: Research suggests that general parenting dimensions and styles are
      associated with children's BMI, but directionality in this relationship remains
      unknown. Moreover, there has been little attention to the influences of both
      mothers' and fathers' parenting. We aimed to examine reciprocal relationships
      between maternal and paternal parenting consistency and child BMI. METHODS:
      Participants were 4002 children and their parents in the population-based
      Longitudinal Study of Australian Children. Mothers and fathers self-reported
      parenting consistency, and children's BMI was measured at 4 biennial waves
      starting at age 4 to 5 years in 2004. Bidirectionality between parenting and
      child BMI was examined by using regression analyses in cross-lagged models.
      RESULTS: The best-fitting models indicated a modest influence from parenting to
      child BMI, whereas no support was found for bidirectional influences. For
      mothers, higher levels of parenting consistency predicted lower BMI in children
      from Waves 1 to 2 and 3 to 4; for example, for every SD increase in mothers'
      parenting consistency at Wave 1, child BMIz fell by 0.025 in Wave 2 (95%
      confidence interval: -0.05 to -0.003). For fathers, higher levels of parenting
      consistency were associated with lower child BMI from Waves 1 to 2 and 2 to 3.
      CONCLUSIONS: Parenting inconsistency of mothers and fathers prospectively
      predicted small increases in offspring BMI over 2-year periods across middle
      childhood. However, child BMI did not appear to influence parenting behavior.
      These findings support recent calls for expanding childhood overweight
      interventions to address the broad parenting context while involving both mothers
      and fathers.

PMID- 24276846
TI  - Frequency and variety of inpatient pediatric surgical procedures in the United
      States.
AB  - OBJECTIVE: Pediatric surgical procedures are being performed in a variety of
      hospitals with large differences in surgical volume. We examined the frequency
      and variety of inpatient pediatric surgical procedures in the United States by
      hospital type and geographic region using a nationally representative sample.
      METHODS: The 2009 Kids' Inpatient Database for patients <18 years old was used to
      calculate surgical frequencies by using International Classification of Diseases,
      Ninth Revision, Clinical Modification, (ICD-9-CM) codes. We performed stratified
      analysis by hospital type (free-standing children's hospital, children's unit
      within an adult hospital, and general hospital) and geographic region (South,
      West, Midwest, Northeast) to compare frequencies of surgical procedures. RESULTS:
      A total of 216 081 procedures were projected for 2009 with the top 20 procedures
      accounting for >90% of cases. As many as 40% of all pediatric inpatient surgical
      procedures are being performed in adult general hospitals. Infrequent complex low
      volume neonatal surgical procedures (pullthrough for Hirschsprung disease,
      surgery for malrotation, esophageal atresia repair, and diaphragmatic hernia
      repair) were 6.8 to 16 times more likely to occur in a children's hospital.
      Significant regional variation in procedure frequency rates occurred for
      appendectomy and cholecystectomy. CONCLUSIONS: This report is the first to
      characterize pediatric surgical inpatient volume in the United States. Such data
      may influence the distribution of pediatric surgeons, number of trainees, and
      training curricula for pediatric surgeons, pediatricians, general surgeons and
      other surgical specialists who might operate on children. In addition, it raises
      the question of whether complex pediatric surgical procedures should preferably
      be performed at dedicated high volume children's hospitals.

PMID- 24276847
TI  - Neuraminidase inhibitors for critically ill children with influenza.
AB  - OBJECTIVE: Timely treatment with neuraminidase inhibitor (NAI) drugs appears to
      improve survival in adults hospitalized with influenza. We analyzed California
      surveillance data to determine whether NAI treatment improves survival in
      critically ill children with influenza. METHODS: We analyzed data abstracted from
      medical records to characterize the outcomes of patients aged 0 to 17 years
      hospitalized in ICUs with laboratory-confirmed influenza from April 3, 2009,
      through September 30, 2012. RESULTS: Seven hundred eighty-four influenza cases
      aged <18 years hospitalized in ICUs had information on treatment. Ninety percent
      (532 of 591) of cases during the 2009 H1N1 pandemic (April 3, 2009-August 31,
      2010) received NAI treatment compared with 63% (121 of 193) of cases in the
      postpandemic period (September 1, 2010-September 30, 2012; P < .0001). Of 653
      cases NAI-treated, 38 (6%) died compared with 11 (8%) of 131 untreated cases
      (odds ratio = 0.67, 95% confidence interval: 0.34-1.36). In a multivariate model
      that included receipt of mechanical ventilation and other factors associated with
      disease severity, the estimated risk of death was reduced in NAI-treated cases
      (odds ratio 0.36, 95% confidence interval: 0.16-0.83). Treatment within 48 hours
      of illness onset was significantly associated with survival (P = .04). Cases with
      NAI treatment initiated earlier in illness were less likely to die. CONCLUSIONS:
      Prompt treatment with NAIs may improve survival of children critically ill with
      influenza. Recent decreased frequency of NAI treatment of influenza may be
      placing untreated critically ill children at an increased risk of death.

PMID- 24276848
TI  - Time to get on the bus: children's surgery and where we need to go.

PMID- 24276849
TI  - Role of enzymatic and non-enzymatic processes in H2O2 removal by rat liver and
      heart mitochondria.
AB  - We compared the capacity of rat liver and heart mitochondria to remove
      exogenously produced H2O2, determining their ability to decrease fluorescence
      generated by H2O2 detector system. In the absence of substrates, liver and heart
      mitochondria removed H2O2 at similar rates. Respiratory substrate addition
      increased removal rates, indicating a respiration-dependent process. Moreover,
      the rates were higher with pyruvate/malate than with succinate and in heart than
      in liver mitochondria. Generally, the changes in H2O2 removal rates mirrored
      those of H2O2 release rates excluding the possibility that endogenous and
      exogenous H2O2 competed for the removing system. This idea was supported by the
      observation that the heaviest of three liver mitochondrial fractions exhibited
      the highest rates of both H2O2 release and removal. Pharmacological inhibition
      showed tissue-linked differences in antioxidant enzyme contribution to H2O2
      removal which were consistent with the differences in antioxidant system
      activities. The enzymatic processes accounted only in part for net H2O2 removal
      and the non-enzymatic ones participated to H2O2 scavenging to a degree that was
      higher for heart than for liver mitochondria. The idea that non-enzymatic
      scavenging was due in great part to hemoproteins action was consistent with
      observation that the concentration of cytochromes, in particular cytochrome c,
      was higher in heart mitochondria. Indirect support was also obtained by a
      technique of enhanced luminescence, utilizing the capacity of cytochrome c/H2O2
      to catalyze the luminol oxidation, which showed that luminescence response to an
      oxidative challenge was higher in heart mitochondria. 

PMID- 24276850
TI  - Patterns of cognitive performance in Subcortical Ischemic Vascular Disease
      (SIVD).
AB  - Subcortical ischemic vascular disease (SIVD) is characterized by extensive white
      matter lesions and lacunar infarcts in deep gray matter. The aim of this study
      was to investigate patterns of cognitive impairment in patients with SIVD. In a
      retrospective analysis, the authors compared the cognitive performance of 58
      patients meeting MRI-defined criteria for SIVD (26 women; 47.3%) with age- and
      gender-matched control subjects. SIVD patients showed impairments in measures of
      verbal fluency, verbal memory, speed of cognitive processing, and divided
      attention. There were no significant differences in constructional praxis,
      figurative memory, verbal recognition memory, or semantic processing. 

PMID- 24276853
TI  - Evolution of the treatment paradigm for patients with metastatic castration
      resistant prostate cancer.
AB  - As recently as 2004, treatment options for men with metastatic castration
      resistant prostate cancer (mCRPC) were limited, with docetaxel the only approved
      agent conferring a survival benefit. The therapeutic landscape is now very
      different, with several agents demonstrating prolonged survival since 2010. New
      agents for the treatment of mCRPC include sipuleucel-T, cabazitaxel, abiraterone
      acetate, enzalutamide and radium-223. All are now approved for use in this
      patient group, although the specific licensing terms vary between agents. In
      addition, denosumab may have utility in patients with bone metastases. A number
      of novel agents are also in development with promising initial results. However,
      because these treatment options have proliferated rapidly, there is currently a
      paucity of clinical evidence regarding their optimal sequencing. Selection of an
      appropriate treatment option should take into consideration disease
      characteristics, drug availability and patient choice. In summary, we discuss
      several new treatment options available for mCRPC and their integration into the
      current treatment paradigm. 

PMID- 24276854
TI  - "All I want for christmas is two": the advent of novel fixed-combination inhalers
      for COPD and outlook for 2014.

PMID- 24276855
TI  - CORR Insights(r): Association of a modified frailty index with mortality after
      femoral neck fracture in patients aged 60 years and older.

PMID- 24276852
TI  - Small Rho GTPases in the control of cell shape and mobility.
AB  - Rho GTPases are a class of evolutionarily conserved proteins comprising 20
      members, which are predominantly known for their role in regulating the actin
      cytoskeleton. They are primarily regulated by binding of GTP/GDP, which is again
      controlled by regulators like GEFs, GAPs, and RhoGDIs. Rho GTPases are thus far
      well known for their role in the regulation of actin cytoskeleton and migration.
      Here we present an overview on the role of Rho GTPases in regulating cell shape
      and plasticity of cell migration. Finally, we discuss the emerging roles of
      ubiquitination and sumoylation in regulating Rho GTPases and cell migration. 

PMID- 24276857
TI  - Higher Charlson Comorbidity Index Scores are associated with readmission after
      orthopaedic surgery.
AB  - BACKGROUND: The Charlson Comorbidity Index (CCI) originally was developed to
      predict mortality within 1 year of hospital admission in patients without trauma.
      As it includes factors associated with medical and surgical complexities, it also
      may be useful as a predictive tool for hospital readmission after orthopaedic
      surgery, but to our knowledge, this has not been studied. QUESTIONS/PURPOSES: We
      asked whether an increased score on the CCI was associated with (1) readmission,
      (2) an increased risk of surgical site infection or other adverse events, (3)
      transfusion risk, or (4) mortality after orthopaedic surgery. METHODS: A total of
      30,129 orthopaedic surgeries performed between 2008 and 2011 without any
      orthopaedic surgery in the preceding 30 days were analyzed. International
      Classification of Diseases, 9(th) Revision codes were used to identify diagnoses,
      procedures, surgery-related adverse events, surgical site infection, and
      comorbidities as listed in the updated and reweighted CCI. A total of 913
      patients (3.0%) were readmitted within 30 days after discharge; in 393 (1.4%)
      patients adverse events occurred; 417 patients (1.4%) had a surgical site
      infection develop; 211 (0.7%) needed transfusions, and 56 (0.2%) died within 30
      days after surgery. Ordinary least squares regression analyses were used to
      determine whether the CCI was associated with these outcomes. RESULTS: The CCI
      accounted for 10% of the variation in readmissions. Every point increase in CCI
      score added an additional 0.45% risk in readmission for patients undergoing
      arthroplasty, 0.63% for patients undergoing trauma surgery, and 0.9% risk for
      patients undergoing spine surgery (all p < 0.01). The CCI was not associated with
      surgical site infection or other adverse events, but accounted for 8% of the
      variation in transfusion rate and 10% of the variation in mortality within 30
      days of surgery. CONCLUSIONS: The CCI can be used to estimate the risk of
      readmission after arthroplasty, hand and upper extremity surgery, spine surgery,
      and trauma surgery. It also can be used to estimate the risk of transfusion after
      arthroplasty, spine, trauma, and oncologic orthopaedic surgery and the risk of
      mortality after shoulder, trauma, and oncologic orthopaedic surgery. LEVEL OF
      EVIDENCE: Level IV, prognostic study. See the Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24276851
TI  - Something old, something new and something borrowed: emerging paradigm of insulin
      like growth factor type 1 receptor (IGF-1R) signaling regulation.
AB  - The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the
      development and progression of cancer; however, therapeutics targeting it have
      had disappointing results in the clinic. As a receptor tyrosine kinase (RTK), IGF
      1R is traditionally described as an ON/OFF system, with ligand stabilizing the ON
      state and exclusive kinase-dependent signaling activation. Newly added to the
      traditional model, ubiquitin-mediated receptor downregulation and degradation was
      originally described as a response to ligand/receptor interaction and thus
      inseparable from kinase signaling activation. Yet, the classical model has proven
      over-simplified and insufficient to explain experimental evidence accumulated
      over the last decade, including kinase-independent signaling, unbalanced
      signaling, or dissociation between signaling and receptor downregulation. Based
      on the recent findings that IGF-1R "borrows" components of G-protein coupled
      receptor (GPCR) signaling, including beta-arrestins and G-protein-related
      kinases, we discuss the emerging paradigm for the IGF-1R as a functional RTK/GPCR
      hybrid, which integrates the kinase signaling with the IGF-1R canonical GPCR
      characteristics. The contradictions to the classical IGF-1R signaling concept as
      well as the design of anti-IGF-1R therapeutics treatment are considered in the
      light of this paradigm shift and we advocate recognition of IGF-1R as a valid
      target for cancer treatment. 

PMID- 24276858
TI  - Patients with hip osteoarthritis have a phenotype with high bone mass and low
      lean body mass.
AB  - BACKGROUND: Although hip osteoarthritis (OA) is common, its etiology is poorly
      understood. Specifically, it is not known whether hip OA is associated with
      abnormal relationships among the anthropometric and musculoskeletal
      characteristics that are associated with OA in general. QUESTIONS: We asked
      whether patients with primary hip OA have a phenotype with higher bone mineral
      density (BMD), higher BMI, larger skeletal size, lower lean body mass, and higher
      fat content. MATERIAL AND METHODS: We included 30 women and 32 men (mean age, 66
      years; range, 42-84 years) with primary hip OA and 96 women and 91 men as control
      subjects. Dual energy x-ray absorptiometry was used to measure total body BMD
      (g/cm(2)), femoral neck width (cm), fat and lean mass (%), and BMI (kg/m(2)). Z
      scores were calculated for each individual. Data are presented as means with 95%
      CI. RESULTS: Women with hip OA had the following Z scores: total body BMD 0.6
      (0.3, 1.0); BMI 0.6 (0.2, 1.0); femoral neck width 0.2 (-0.6, 1.0); percent total
      body lean mass -0.9 (-1.2, -0.5); and percent total body fat mass 0.6 (0.2, 0.9).
      Men with hip OA had the following mean Z scores: total body BMD 0.5 (0.0, 1.0);
      BMI 0.8 (0.3, 1.3); femoral neck width 0.4 (0.01, 0.9); percent total body lean
      mass -0.8 (-1.1, -0.5); and percent total body fat mass 0.5 (0.2, 0.8).
      CONCLUSIONS: Women and men with idiopathic hip OA have a phenotype with higher
      BMD, higher BMI, proportionally higher fat mass, and proportionally lower lean
      body mass. Men also have a larger skeletal size. CLINICAL RELEVANCE: A higher BMD
      may lead to a stiffer bone and a proportionally lower lean body mass to lower
      joint-protective ability, both traits probably predisposing for hip OA.

PMID- 24276859
TI  - Fairness to all: gender and sex in scientific reporting.

PMID- 24276860
TI  - The infinite possible growth ambients that support single-wall carbon nanotube
      forest growth.
AB  - We report the virtually infinite possible carbon feedstocks which support the
      highly efficient growth of single-wall carbon nanotubes (SWCNTs) using on the
      water-assisted chemical vapor deposition method. Our results demonstrate that
      diverse varieties of carbon feedstocks, in the form of hydrocarbons, spanning
      saturated rings (e.g. trans-deca-hydronaphthalene), saturated chains (e.g.
      propane), unsaturated rings (e.g. dicyclopentadiene), and unsaturated chains
      (e.g. ethylene) could be used as a carbon feedstocks with SWCNT forests with
      heights exceeding 100 ums. Further, we found that all the resultant SWCNTs
      possessed similar average diameter indicating that the diameter was mainly
      determined by the catalyst rather than the carbon feedstock within this synthetic
      system. A demonstration of the generality was the synthesis of a carbon nanotube
      forest from a highly unorthodox combination of gases where trans
      decahydronaphthalene acted as the carbon feedstock and benzaldehyde acted as the
      growth enhancer.

PMID- 24276861
TI  - Megabladder mouse model of congenital obstructive nephropathy: genetic etiology
      and renal adaptation.
AB  - Congenital obstructive nephropathy remains one of the leading causes of chronic
      renal failure in children. The direct link between obstructed urine flow and
      abnormal renal development and subsequent dysfunction represents a central
      paradigm of urogenital pathogenesis that has far-reaching clinical implications.
      Even so, a number of diagnostic, prognostic, and therapeutic quandaries still
      exist in the management of congenital obstructive nephropathy. Studies in our
      laboratory have characterized a unique mutant mouse line that develops in utero
      megabladder, variable hydronephrosis, and progressive renal failure. Megabladder
      mice represent a valuable functional model for the study of congenital
      obstructive nephropathy. Recent studies have begun to shed light on the genetic
      etiology of mgb (-/-) mice as well as the molecular pathways controlling disease
      progression in these animals. 

PMID- 24276862
TI  - Validation of the CKiD formulae to estimate GFR in children post renal
      transplant.
AB  - BACKGROUND: The Chronic Kidney Disease in Children (CKiD) study reported new
      formulae to estimate glomerular filtration rate (eGFR). The study reported here
      aimed to assess the accuracy of these formulae in estimating levels and changes
      in GFR in pediatric renal transplant recipients and generate a new formula in our
      cohort. METHODS: Two hundred and fifty-two studies of plasma disappearance of
      (125)I-iothalamate (CIO) were used to measure GFR in 155 renal transplant
      recipients. The CKiD bedside formula (CKiD-BS) was compared with CIO. A mixed
      logistic regression model was fit to evaluate the performance of estimating
      change in posttransplant CIO using CKiD-BS. We used mixed-effects linear
      regression to fit a multiplicative model of CIO. The CKiD cystatin-C-based
      formula (CKiD-Cys) was also used for comparison in 32 additional transplant
      recipients. Comparisons were made using Bland-Altman plots. RESULTS: CKiD-BS
      underestimates CIO by 20 % for GFR >25 ml/min per 1.73 m(2). Percentage change in
      CKiD-BS performed reasonably well in estimating 15 % change of CIO beginning 6
      months posttransplant [area under the curve (AUC) = 0.791)] The multiplicative
      constant in the CKiD-BS was recalibrated [R-Bedside = 0.461 * ht(cm)/SCr).]A GFR
      model [GFR-M) = 10.73 * [(ht(cm)]0.51/(SCr)0.90 * (BUN)0.23] has higher
      specificity but similar sensitivity for CIO compared with R-Bedside. CKiD-Cys
      overestimates CIO by 10 ml/min per 1.73 m(2) across a broad range of GFR.
      CONCLUSIONS: In our cohort, the CKiD-BS underestimates CIO; however, changes in
      CKiD-BS can be used to estimate changes in CIO. CKiD-Cys overestimates CIO and is
      not accurate in estimating CIO.

PMID- 24276863
TI  - Urolithiasis in an infant with propionic acidemia: answer.

PMID- 24276864
TI  - Genetic studies of the basisdiomycete Agrocybe aegerita : Part 2: Genetic control
      of fruit body formation and its practical implications.
AB  - In the edible white rot fungus Agrocybe aegerita the threshold from mycelial
      growth to fruit body formation is under control of a single gene in both
      monokaryons and dikaryons.The allele su opens the pathway for fruiting and allows
      the subsequent expression of the fruiter genes fi(+) (fruit body initials) and fb
      (+) (fruit bodies). Its allele, su (+), suppresses monokaryotic fruiting
      completely and restricts dikaryotic fruiting drastically.The detection of this
      threshold gene su (+)/su and its action and interactions has practical
      implication in that an opportunity for concerted breeding is created.First
      results indicate that the fruiter genes are involved in two essential parameters
      of productivity. Both time of fruiting and biomass production depend on the two
      fruiter genes fi (+) and fb (+).Comparable results obtained with two other
      basidiomycetes suggest that the genetic control of fruiting in Agrocybe aegerita
      is a general mechanism which may be made use of in breeding work with other
      basidiomycetes of economic value. 

PMID- 24276865
TI  - The early growth of artificially reared American lobsters : Part 1: Genetic
      parameters within environments.
AB  - Twenty families of the lobster, Homarus americanus, were reared at 10 degrees ,
      15 degrees  and 20 degrees C with and without bilateral eye-stalk-ablation. At 20
      degrees C both eye-stalk-ablated and non-eye-stalk-ablated lobsters from each
      family were assigned to one of two dietary treatments: 1) frozen whole brine
      shrimp, or 2) a diet of cheap, local constituents. The means of growth traits
      improved while viability decreased with increasing temperature. The ablation
      technique shows promise since improved performance for growth was apparent in eye
      stalk ablated lobsters, but mortality was greater. Important genetic variation of
      all traits was found in each of the environments tested. The genetic correlations
      between growth traits were reinforcing, but the correlations between growth and
      viability traits were mainly negative. Ease and reliability of measurement should
      be considered when choosing growth traits in any artifical selection program. 

PMID- 24276866
TI  - Chromosome banding and heterochromatin in Vicia faba.
AB  - The distribution of bands in Vicia faba (broad bean) root-tip chromosomes as
      shown by acid treatment, quinacrine mustard fluorescence, SSC-Giemsa banding and
      orcein banding is documented. These bands coincide with the position of
      heterochromatin revealed by cold treatment. Heterochromatin in the large M
      chromosome is located in two areas: (a) around the centromere and (b) adjacent to
      the secondary constriction. Heterochromatin in the smaller, sub-telocentric S
      chromosomes is located in the intercalary and proximal areas of their long arms
      and in the short arm of two chromosomes. Most of the observed bands were not
      exclusive to one treatment but could be recognized in chromosomes prepared by
      several methods. The variable expression of particular chromosome segments with
      different banding techniques testifies to the existence of several classes of
      heterochromatin. 

PMID- 24276867
TI  - Con A - Peroxidase method: an improved procedure for staining S-glycoproteins in
      cellulose-acetate electrofocusing in crucifers.
AB  - In the analysis of stigma glycoproteins by cellulose acetate electrofocusing in
      self-incompatible crucifers, the staining method of the glycoproteins, described
      in the earlier report, has been improved by using Con A - peroxidase reactions to
      obtain a permanent profile of band patterns which are visible under day-light
      conditions. Identifying S alleles by the corresponding S-glycoproteins can be
      facilitated by the present S-glycoprotein analysis. 

PMID- 24276868
TI  - Genetic variability in Plantago species in relation to their ecology : Part 1:
      Genetic analysis of the allozyme variation in P. major subspecies.
AB  - A survey of enzyme variability in several populations of Plantago major in the
      Netherlands has been made. Nine of 36 loci were found to be polymorphic. The most
      extensively studies population showed 7 polymorphic loci (19%). The average
      heterozygosity was 0.005, a low value since P. major is predominantly inbreeding;
      a first estimate of the outcrossing rate is only 10%. All nine variable loci show
      simple Mendelian inheritance, seven of them could be placed into four different
      linkage groups. Marked differences in allele frequencies were found between two
      subspecies: ssp. major and ssp. pleiosperma. Two enzyme loci possess subspecies
      specific alleles, Pgm-1 and Got-1. The most likely explanation of this phenomenon
      is the existence of fitness differences, caused either by the enzyme loci
      themselves or by linked loci. 

PMID- 24276869
TI  - The effect of isozyme selection on metric characters in an interspecific
      backcross of tomato - basis of an early screening procedure.
AB  - The extent of correlation was estimated between isozyme genotypes and the four
      widely segregating characters - leaf segment W/L ratio, stigma exsertion, fruit
      weight, and seed weight - in the first backcross of F1 Lycopersicon esculentum x
      Solanum pennellii to the former parent. The inbred parents differ in their
      alleles at the 12 tested isozymic loci, which are known to mark a minimum of
      eight of the twelve tomato chromosomes. Based on the isozyme data, a mean
      heterozygosity value, -H, was calculated which estimates the proportion of
      pennillii alleles in each individual. Correlations between mean heterozygosity
      and observed levels of each quantitative trait were highly significant and
      positive or negative as expected from the relative parental values. Plants with
      the lowest mean heterozygosity - i.e., closest to the esculentum zymotype also
      had mean values closest to those of this parent amongst the whole backcross
      population for each of the quantitative traits.Bivariate and multiple regression
      analysis was used to evaluate the ability of isozymes vs diagnostic morphological
      characters to estimate the portion of recurrent parent genes carried in each
      backcross individual. The results suggest that isozyme data gives better
      estimates than single diagnostic morphological characters and approach the level
      obtained by combinations of three morphological traits. Since electrophoretic
      determinations are made on small seedlings, selection at that stage can effect
      great savings of space and effort by greatly deminishing the size of the
      population needed at maturity. As such, isozyme selection would precede
      morphological selection but not replace it, thus the predictive value of these
      biochemical markers as well as diagnostic morphological characters could be
      obtained. 

PMID- 24276870
TI  - Discriminating styles (DS) and pollen-mediated pseudo-self-compatibility (PMPSC)
      in Nemesia strumosa Benth. : Part 1: Characteristics and inheritance of DS.
AB  - Nemesia strumosa plants were discovered which had styles capable of
      discriminating among incompatible pollen tubes from different pollinators,
      allowing growth of some but not others. All but 3 of 26 families tested had at
      least some members with discriminating styles (DS). Presence and level of DS was
      independent of S genotype. Plants with pseudo-self-compatiblity (PSC) levels
      greater than 10% had the trait, though many plants with strong DS had PSC levels
      less than 10%. Self pollination of highly DS plants produced mostly DS offspring,
      but of differing sensitivities. Some progenies from crosses between a family of
      highly DS plants and unrelated, probably low DS plants segregated half DS and
      half non-DS, while others consisted of mostly DS or mostly non-DS. The DS
      phenomenon is probably caused by PSC genes. 

PMID- 24276871
TI  - Provocation of mutability in the level of mutation expressed at the pal-rec gene
      in Antirrhinum majus.
AB  - The pallida gene of Antirrhinum majus governs anthocyanin production. The nature
      of the mutability displayed by its unstable allele pal-rec was dramatically
      altered following crosses between two pal-rec pal-rec lines with certain
      separately maintained lines. In both cases a minority of progeny in F1 or F2
      revealed unprecedented infrequent mutability termed 'Low mutability'. These Low
      plants and their sibs showed many areas of contrasting mutability superimposed on
      their initial mutability level. This frequent 'shifting' and Low mutability
      persisted through several generations of offspring obtained by both selfing and
      crossing to a non-mutable tester line. Evidence is presented to suggest a
      hypothesis that the two features of altered mutability are two aspects of the
      same phenomenon caused by joint action of two independent factors J and k, one
      contributed by each parental line at the outcross.A separate gene, eosinea,
      governs anthocyanin type, eos eos plants having pelargonin in place of wild-type
      magenta cyanin. In addition to the previously known simple depression of pal-rec
      to Pal mutation frequency in eos eos plants, eos also influences the action of J
      and k when heterozygous (i.e. Eos eos), thus contributing a basal and a third
      tier of control influencing mutability of pal-rec.Three levels of control are
      thus identified, the middle tier being governed by the partnership of J and k
      producing not a simple change but a complex mutability of mutability. 

PMID- 24276872
TI  - Inheritance of resistance to Okra yellow vein mosaic disease in interspecific
      crosses of Abelmoschus.
AB  - Two Abelmoschus species, viz., A. manihot (L.) Medik and A. manihot (L.) Medik
      ssp. manihot, resistant to Okra yellow vein mosaic (YVM) were crossed to A.
      esculentus cv. 'Pusa Sawani', a susceptible culture. The hybrids were resistant
      and partially fertile. Segregation pattern for disease reaction in F2, BC1 and
      subsequent generations of the two crosses revealed that resistance to YVM is
      controlled by a single dominant gene in each species. 

PMID- 24276873
TI  - Correlated responses to selection for wing length in allozyme systems of
      Drosophila melanogaster.
AB  - Significant changes of genotypic structure in 20 lines selected for wing length
      are detected by analysis of the allelic frequencies of several enzyme loci (XDH,
      LAP-D, EST-6, 1-APH, ADH, alpha-GPDH). These changes are not haphazard but a
      consequence of the effects of selection on the genetic structure of the
      population, since replicate lines always behave in a parallel way. The changes
      are larger in the lines selected for short wings, in which the genetic
      variability decreases considerably. This decrease is the result of selection for
      homozygosity, detected at the allozyme loci, but most probably reflects
      homozygosity of more or less extended chromosomal segments. Selection for wing
      length, especially for short wings, favoured recombinants of the initial founder
      chromosomes. Only in the 1-APH and the EST-6 loci, separated by 11.7 centimorgans
      on the genetic map, do the alleles linked in the founder lines change in parallel
      in the control and long wing lines. The correlated response in the allozyme
      allele frequencies cannot be accounted for by a direct influence of the allozymes
      on the variability in wing length. The changes in the EST-6, 1-APH and perhaps in
      the LAP-D, can be explained by a direct effect of natural selection on the
      allozyme loci, probably in interaction with the effect of selection for wing
      length on linked loci. This last effect seems to be the main factor contributing
      to the change detected in the XDH locus. 

PMID- 24276874
TI  - Effect of selection for spot size on reproduction and body weight in mice.
AB  - Spot size in descendants from the Goodale white-spotted stock of mice responded
      to selection for increased spot size. The realized heritability estimate was
      0.52. However, no correlated response of reproduction to spot size selection was
      found in the present study, nor was there any correlated response among body
      weight variables. 

PMID- 24276875
TI  - Vitamin D and cardiovascular health.

PMID- 24276876
TI  - Cardiac resynchronization therapy: state-of-the-art of current applications,
      guidelines, ongoing trials, and areas of controversy.

PMID- 24276877
TI  - ECG response: November 26, 2013.

PMID- 24276878
TI  - Vertebral body erosion in a 27-year-old woman 12 years after thoracic
      endovascular aortic repair.

PMID- 24276879
TI  - Circulation editors' picks: obesity and cardiovascular disease.

PMID- 24276880
TI  - Letter by Houthuizen et al regarding article, "Clinical impact of persistent left
      bundle-branch block after transcatheter aortic valve implantation with CoreValve
      revalving system".

PMID- 24276882
TI  - Introductory remarks.
AB  - This introductory section briefly highlights the subsequent chapters in the
      context of recent findings and open questions in lymphatic vessel biology. It
      aims to provide a quick overview and orientation in the contents of this
      monograph collection. 

PMID- 24276881
TI  - Response to letter regarding article, "Clinical impact of persistent left bundle
      branch block after transcatheter aortic valve implantation with CoreValve
      revalving system".

PMID- 24276883
TI  - Transcriptional control of lymphatic endothelial cell type specification.
AB  - The lymphatic vasculature is the "sewer system" of our body as it plays an
      important role in transporting tissue fluids and extravasated plasma proteins
      back to the blood circulation and absorbs lipids from the intestinal tract.
      Malfunction of the lymphatic vasculature can result in lymphedema and obesity.
      The lymphatic system is also important for the immune response and is one of the
      main routes for the spreading of metastatic tumor cells. The development of the
      mammalian lymphatic vasculature is a stepwise process that requires the
      specification of lymphatic endothelial cell (LEC) progenitors in the embryonic
      veins, and the subsequent budding of those LEC progenitors from the embryonic
      veins to give rise to the primitive lymph sacs from which the entire lymphatic
      vasculature will eventually be derived. This process was first proposed by
      Florence Sabin over a century ago and was recently confirmed by several studies
      using lineage tracing and gene manipulation. Over the last decade, significant
      advances have been made in understanding the transcriptional control of lymphatic
      endothelial cell type differentiation. Here we summarize our current knowledge
      about the key transcription factors that are necessary to regulate several
      aspects of lymphatic endothelial specification and differentiation. 

PMID- 24276884
TI  - Mechanosensing in developing lymphatic vessels.
AB  - The lymphatic vasculature is responsible for fluid homeostasis, transport of
      immune cells, inflammatory molecules, and dietary lipids. It is composed of a
      network of lymphatic capillaries that drain into collecting lymphatic vessels and
      ultimately bring fluid back to the blood circulation. Lymphatic endothelial cells
      (LECs) that line lymphatic capillaries present loose overlapping intercellular
      junctions and anchoring filaments that support fluid drainage. When interstitial
      fluid accumulates within tissues, the extracellular matrix (ECM) swells and pulls
      the anchoring filaments. This results in opening of the LEC junctions and permits
      interstitial fluid uptake. The absorbed fluid is then transported within
      collecting lymphatic vessels, which exhibit intraluminal valves that prevent
      lymph backflow and smooth muscle cells that sequentially contract to propel
      lymph.Mechanotransduction involves translation of mechanical stimuli into
      biological responses. LECs have been shown to sense and respond to changes in ECM
      stiffness, fluid pressure-induced cell stretch, and fluid flow-induced shear
      stress. How these signals influence LEC function and lymphatic vessel growth can
      be investigated by using different mechanotransduction assays in vitro and to
      some extent in vivo.In this chapter, we will focus on the mechanical forces that
      regulate lymphatic vessel expansion during embryonic development and possibly
      secondary lymphedema. In mouse embryos, it has been recently shown that the
      amount of interstitial fluid determines the extent of lymphatic vessel expansion
      via a mechanosensory complex formed by beta1 integrin and vascular endothelial
      growth factor receptor-3 (VEGFR3). This model might as well apply to secondary
      lymphedema. 

PMID- 24276885
TI  - Plasticity of airway lymphatics in development and disease.
AB  - The dynamic nature of lymphatic vessels is reflected by structural and functional
      modifications that coincide with changes in their environment. Lymphatics in the
      respiratory tract undergo rapid changes around birth, during adaptation to air
      breathing, when lymphatic endothelial cells develop button-like intercellular
      junctions specialized for efficient fluid uptake and transport. In inflammatory
      conditions, lymphatic vessels proliferate and undergo remodeling to accommodate
      greater plasma leakage and immune cell trafficking. However, the newly formed
      lymphatics are abnormal, and resolution of inflammation is not accompanied by
      complete reversal of the lymphatic vessel changes back to the baseline. As the
      understanding of lymphatic plasticity advances, approaches for eliminating the
      abnormal vessels and improving the functionality of those that remain move closer
      to reality. This chapter provides an overview of what is known about lymphatic
      vessel growth, remodeling, and other forms of plasticity that occur during
      development or inflammation, with an emphasis on the respiratory tract. Also
      addressed is the limited reversibility of changes in lymphatics during the
      resolution of inflammation. 

PMID- 24276886
TI  - Regulation of lymphatic vasculature by extracellular matrix.
AB  - The extracellular matrix (ECM) is a complex but highly organized network of
      macromolecules with different physical, biochemical, and mechanical properties.
      In addition to providing structural support to tissues, it regulates a variety of
      cellular responses during development and tissue homeostasis. Interactions
      between the lymphatic vessels and their ECM are starting to be recognized as
      important modulators of lymphangiogenesis. Here, we review the current knowledge
      of the structure and composition of the ECM of lymphatic vessels and discuss the
      role of individual matrix components and their cell surface receptors in
      regulating lymphatic vascular development and function. 

PMID- 24276887
TI  - Interplay of mechanotransduction, FOXC2, connexins, and calcineurin signaling in
      lymphatic valve formation.
AB  - The directional flow of lymph is maintained by hundreds of intraluminal lymphatic
      valves. Lymphatic valves are crucial to prevent lymphedema, accumulation of fluid
      in the tissues, and to ensure immune surveillance; yet, the mechanisms of valve
      formation are only beginning to be elucidated. In this chapter, we will discuss
      the main steps of lymphatic valve morphogenesis, the important role of
      mechanotransduction in this process, and the genetic program regulated by the
      transcription factor Foxc2, which is indispensable for all steps of valve
      development. Failure to form mature collecting lymphatic vessels and valves
      causes the majority of postsurgical lymphedema, e.g., in breast cancer patients.
      Therefore, this knowledge will be useful for diagnostics and development of
      better treatments of secondary lymphedema. 

PMID- 24276888
TI  - Development of secondary lymphoid organs in relation to lymphatic vasculature.
AB  - Although the initial event in lymphatic endothelial specification occurs slightly
      before the initiation of lymph node formation in mice, the development of
      lymphatic vessels and lymph nodes occurs within the same embryonic time frame.
      Specification of lymphatic endothelial cells starts around embryonic day 10
      (E10), followed by endothelial cell budding and formation of the first lymphatic
      structures. Through lymphatic endothelial cell sprouting these lymph sacs give
      rise to the lymphatic vasculature which is complete by E15.5 in mice. It is
      within this time frame that lymph node formation is initiated and the first
      structure is secured in place. As lymphatic vessels are crucially involved in the
      functionality of the lymph nodes, the recent insight that both structures depend
      on common developmental signals for their initiation provides a molecular
      mechanism for their coordinated formation. Here, we will describe the common
      developmental signals needed to properly start the formation of lymphatic vessels
      and lymph nodes and their interdependence in adult life. 

PMID- 24276889
TI  - Platelets in lymph vessel development and integrity.
AB  - Blood platelets have recently been proposed to play a critical role in the
      development and repair of the lymphatic system. The platelet C-type lectin
      receptor CLEC-2 and its ligand, the transmembrane protein Podoplanin, which is
      expressed at high levels on lymphatic endothelial cells (LECs), are required to
      prevent mixing of the blood and lymphatic vasculatures during mid-gestation. A
      similar defect is seen in mice deficient in the tyrosine kinase Syk, which plays
      a vital role in mediating platelet activation by CLEC-2. Furthermore, blood
      lymphatic mixing is also present in mice with platelet-/megakaryocyte-specific
      deletions of CLEC-2 and Syk, suggesting that the phenotype is platelet in origin.
      The molecular basis of this effect is not known, but it is independent of the
      major platelet receptors that support hemostasis, including integrin
      alphaIIbbeta3 (GPIIb-IIIa). Radiation chimeric mice reconstituted with CLEC-2
      deficient or Syk-deficient bone marrow exhibit blood-lymphatic mixing in the
      intestines, illustrating a role for platelets in repair and growth of the
      lymphatic system. In this review, we describe the events that led to the
      identification of this novel role of platelets and discuss possible molecular
      mechanisms and the physiological and pathophysiological significance. 

PMID- 24276890
TI  - Interactions of immune cells and lymphatic vessels.
AB  - In addition to fluid and lipid absorption, immune cell trafficking has now become
      recognized as one of the major functions of the lymphatic system. Recently,
      several critical roles of the lymphatic vessels (LVs) in modulating immune
      reactions during both physiological and pathological conditions have been
      emerging. As LVs serve as conduits for immune cells, they come to closely
      interact with macrophages/monocytes, dendritic cells, and T and B lymphocytes.
      Accumulating evidences indicate that reciprocal interactions between the LVs and
      immune cells exist which cause considerable influence over the process of immune
      cell migration, LV growth, and ultimately certain immune reactions. This chapter
      discusses on the interactions of macrophages/monocytes and dendritic cells with
      peripheral LVs and on those of sinusoidal macrophages and T and B lymphocytes
      with lymph node LVs. 

PMID- 24276891
TI  - Lymphatic vessels in the development of tissue and organ rejection.
AB  - The lymphatic vascular system-amongst other tasks-is critically involved in the
      regulation of adaptive immune responses as it provides an important route for APC
      trafficking to secondary lymphatic organs. In this context, the cornea, which is
      the transparent and physiologically avascular "windscreen" of the eye, has served
      as an excellent in vivo model to study the role of the blood and lymphatic
      vasculature in mediating allogenic immune responses after transplantation.
      Especially the mouse model of high-risk corneal transplantation, where corneal
      avascularity is abolished by a severe inflammatory stimulus prior to
      keratoplasty, allows for comparison to other transplantations performed in
      primarily vascularized tissues and solid organs. Using this model, we recently
      demonstrated that especially lymphatic vessels, but not blood vessels, define the
      high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment
      significantly promotes corneal allograft survival. Since evidence for
      lymphangiogenesis and its potential association with graft rejection is nowadays
      also present in solid organ transplantation, studies are currently addressing the
      potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic
      concept also in solid organ grafting with promising initial results. 

PMID- 24276892
TI  - The role of neuropilin-1/semaphorin 3A signaling in lymphatic vessel development
      and maturation.
AB  - During development, the lymphatic and the blood vascular system form highly
      branched networks that show extensive architectural similarities with the
      peripheral nervous system. Increasing evidence suggests that the vascular and the
      nervous systems share signaling pathways to overcome common challenges such as
      guidance of growth and patterning. Semaphorins, a large group of proteins
      originally identified as axon guidance molecules with repelling function, and
      their receptors, neuropilins and plexins, have recently also been implicated in
      vascular development. Here, we summarize the role of semaphorins and their
      receptors in angiogenesis and lymphangiogenesis, with an emphasis on neuropilin
      1/semaphorin 3A interactions in lymphatic vessel maturation and valve formation.
      Understanding the basic principles of lymphatic vessel development and maturation
      might facilitate the development of therapies for the treatment of human diseases
      associated with lymphedema. 

PMID- 24276893
TI  - A fisheye view on lymphangiogenesis.
AB  - Zebrafish have been widely used to study vasculogenesis and angiogenesis, and the
      vascular system is one of the most intensively studied organ systems in teleosts.
      It is a little surprising, therefore, that the development of the zebrafish
      lymphatic network has only been investigated in any detail for less than a decade
      now. In those last few years, however, significant progress has been made. Due to
      favorable imaging possibilities within the early zebrafish embryo, we have a very
      good understanding of what cellular behavior accompanies the formation of the
      lymphatic system and which cells within the vasculature are destined to
      contribute to lymphatic vessels. The migration routes of future lymphatic
      endothelial cells have been monitored in great detail, and a number of transgenic
      lines have been developed that help to distinguish between arterial, venous, and
      lymphatic fates in vivo. Furthermore, both forward and reverse genetic tools have
      been systematically employed to unravel which genes are involved in the process.
      Not surprisingly, a number of known players were identified (such as vegfc and
      flt4), but work on zebrafish has also distinguished genes and proteins that had
      not previously been connected to lymphangiogenesis. Here, we will review these
      topics and also compare the equivalent stages of lymphatic development in
      zebrafish and mice. We will, in addition, highlight some of those studies in
      zebrafish that have helped to identify and to further characterize human disease
      conditions. 

PMID- 24276894
TI  - Visualization of lymphatic vessel development, growth, and function.
AB  - Despite their important physiological and pathophysiological functions, lymphatic
      endothelial cells and lymphatic vessels remain less well studied compared to the
      blood vascular system. Lymphatic endothelium differentiates from venous blood
      vascular endothelium after initial arteriovenous differentiation. Only recently
      by the use of light sheet microscopy, the precise mechanism of separation of the
      first lymphatic endothelial progenitors from the cardinal vein has been described
      as delamination followed by mesenchymal cell migration of lymphatic endothelial
      cells. Dorsolaterally of the embryonic cardinal vein, lymphatic endothelial cells
      reaggregate to form the first lumenized lymphatic vessels, the dorsal peripheral
      longitudinal vessel and the more ventrally positioned primordial thoracic duct.
      Despite this progress in our understanding of the first lymph vessel formation,
      intravital observation of lymphatic vessel behavior in the intact organism,
      during development and in the adult, is prerequisite to a precise understanding
      of this tissue. Transgenic models and two-photon microscopy, in combination with
      optical windows, have made live intravital imaging possible: however, new imaging
      modalities and novel approaches promise gentler, more physiological, and longer
      intravital imaging of lymphatic vessels. 

PMID- 24276895
TI  - Clinical disorders of primary malfunctioning of the lymphatic system.
AB  - Primary lymphedema is defined as lymphedema caused by dysplasia of the lymph
      vessels. This complex group of diseases is discussed in detail from a clinical
      perspective. A review of the epidemiology and classification of lymphedema on the
      backdrop of its clinical presentation reveals weaknesses of the present
      classification system, which, however, is the basis for the choice of optimal
      patient care. Non-syndrome and syndrome types of primary lymphedema are presented
      in detail and related molecular findings are summarized. 

PMID- 24276896
TI  - An agent-based modeling approach for determining corn stover removal rate and
      transboundary effects.
AB  - Bioenergy production involves different agents with potentially different
      objectives, and an agent's decision often has transboundary impacts on other
      agents along the bioenergy value chain. Understanding and estimating the
      transboundary impacts is essential to portraying the interactions among the
      different agents and in the search for the optimal configuration of the bioenergy
      value chain. We develop an agent-based model to mimic the decision making by
      feedstock producers and feedstock-to-biofuel conversion plant operators and
      propose multipliers (i.e., ratios of economic values accruing to different
      segments and associated agents in the value chain) for assessing the
      transboundary impacts. Our approach is generic and thus applicable to a variety
      of bioenergy production systems at different sites and geographic scales. We
      apply it to the case of producing ethanol using corn stover in Iowa, USA. The
      results from the case study indicate that stover removal rate is site specific
      and varies considerably with soil type, as well as other factors, such as stover
      price and harvesting cost. In addition, ethanol production using corn stover in
      the study region would have strong positive ripple effects, with the values of
      multipliers varying with greenhouse gas price and national energy security
      premium. The relatively high multiplier values suggest that a large portion of
      the value associated with corn stover ethanol production would accrue to the
      downstream end of the value chain instead of stover producers. 

PMID- 24276897
TI  - Detection of replication initiation by a replicon family in DNA of synchronized
      pea (Pisum sativum) root cells using benzoylated naphthoylated DEAE-cellulose
      chromatography.
AB  - Fractionated replicating DNA from pea was obtained from both synchronized cells
      just starting replication and from carbohydrate-starved cells ending replication.
      Benzoylated naphthoylated DEAE-cellulose chromatography of pulse-labeled DNA
      digested with EcoR I gave evidence that a family of replicons initiated
      replication 45 to 60 min after synchronized cells were released from the G1/S
      phase boundary. DNA from cells labeled in late S phase, on the other hand, showed
      no signs of additional replication initiations before entering G2 phase. Results
      with DNA from both early and late S phase cells comply with a model based on the
      premise that with short pulses of [(3)H]-thymidine the isotope is localized at
      replication forks and that longer pulses label both replication forks and
      recently replicated segments of double-stranded DNA. The model applies only to
      DNA subjected to fragmentation before chromatography.The results also suggest
      that benzoylated naphthoylated DEAE-cellulose chromatography is a useful means to
      isolate origins and replication forks from synchronized plant cells. 

PMID- 24276898
TI  - Location of the replication origin in the 9-kb repeat size class of rDNA in pea
      (Pisum sativum).
AB  - The replication origin of the 9-kb rDNA repeat size class of pea (Pisum sativum
      cv. Alaska) was identified by benzoylated naphthoylated DEAE-cellulose column
      chromatography and Southern blotting procedures. The origin is located at or near
      a 0.19-kb EcoR I fragment in the non-transcribed spacer region between the 25S
      and 18S rRNA genes. Identification of the origin was based on three criteria: (i)
      an enrichment of the 0.19-kb fragment in replicating rDNA from asynchronously
      dividing root meristematic cells, (ii) the scarcity of the 0.19-kb fragment in
      rDNA from non-dividing carbohydrate starved cells, and (iii) a 60-min periodic
      enrichment of the 0.19-kb fragment in replicating rDNA that temporally coincides
      with the sequential initiation of replication of replicon families in
      synchronized pea root cells. 

PMID- 24276899
TI  - The aurea mutant of tomato is deficient in spectrophotometrically and
      immunochemically detectable phytochrome.
AB  - The aurea locus mutant (au (w)) of tomato contains less than 5% of the level of
      phytochrome in wild-type tissue as measured by in vivo difference spectroscopy.
      Immunoblot analysis using antibodies directed against etiolated-oat phytochrome
      demonstrates that crude extracts of etiolated mutant tissue are deficient in a
      major immunodetectable protein (116 kDa) normally present in the parent wild
      type. Analyses of wild-type tissue extracts strongly indicate that the 116-kDa
      protein is phytochrome by showing that this protein: a) is degraded more rapidly
      in vitro after a brief far-red irradiation than after a brief red irradiation
      (Vierstra RD, Quail PH, Planta 156: 158-165, 1982); b) contains a covalently
      bound chromophore as detected by Zn-chromophore fluorescence on nitrocellulose
      blots; and c) has an apparent molecular mass comparable to phytochrome from other
      species on size exclusion chromatography under non-denaturing conditions. The
      demonstration that the aurea mutant is deficient in this 116-kDa phytochrome
      indicates that the lack of spectrally detectable phytochrome in this mutant is
      the result of a lesion which affects the abundance of the phytochrome molecule as
      opposed to its spectral integrity. 

PMID- 24276900
TI  - The tomato Cab-4 and Cab-5 genes encode a second type of CAB polypeptides
      localized in Photosystem II.
AB  - The photosynthetic apparatus of plant chloroplasts contains two photosystems,
      termed Photosystem I (PSI) and Photosystem II (PSII). Both PSI and PSII contain
      several types of chlorophyll a/b-binding (CAB) polypeptides, at least some of
      which are structurally related. It has been previously shown that multiple genes
      encoding one type of PSII CAB polypeptides exist in the genome of many higher
      plants. In tomato, there are at least eight such genes, distributed in three
      independent loci. Genes encoding a second type of CAB polypeptides have been
      isolated from several plant species, but the precise location of the gene
      products has not been determined. Here we show that tomato has two unlinked genes
      encoding this second type and that this type of CAB polypeptide is also localized
      in PSII. 

PMID- 24276901
TI  - urf13-T of T cytoplasm maize mitochondria encodes a 13 kD polypeptide.
AB  - Polyspecific antibody to a 17 amino acid synthetic peptide from the maize T
      cytoplasm urf13-T mitochondrial open reading frame immunoprecipitated a 13 kD
      polypeptide from (35)S-methionine incorporations of T cytoplasm maize. Male
      fertile, toxin-insensitive mutants in which the urf13-T sequence is deleted do
      not synthesize the 13 kD polypeptide. A mutant designated T-4, which carries a 5
      bp insertion and a premature stop codon, synthesizes a truncated polypeptide,
      corresponding to an open reading frame of 8.3 kD. Thus the 13 kD polypeptide is
      trunctated or absent in mutants expressing male fertility and toxin insensitivity
      in T-cytoplasm maize. 

PMID- 24276902
TI  - Isolation of a cDNA clone for the acyl carrier protein-I of spinach.
AB  - A 715 base pair cDNA clone coding for an acyl carrier protein (ACP) in spinach
      leaves has been isolated and characterized. The amino acid sequence indicated by
      the cDNA sequence closely matches the amino acid sequence of the ACP-I isoform.
      The presence of polyadenylation and DNA sequence coding for a precursor protein
      with a putative transit peptide, and the absence of hybridization between the
      cloned DNA and isolated spinach plastid DNA collectively show that the ACP-I gene
      is nuclear-encoded. The ACP-I cloned DNA did not cross-hybridize with mRNA from
      spinach tissues in which ACP-II has been found. Cross-hybridization with mRNA
      from tissues of Brassica campestris was either weak or undetectable. The cloning
      of an ACP-I gene represents an initial step in the molecular dissection of fatty
      acid synthetase in plants. 

PMID- 24276903
TI  - Transformation of soybean protoplasts from permanent suspension cultures by
      cocultivation with cells of Agrobacterium tumefaciens.
AB  - Cell wall regenerating protoplasts from soybean cells kept in suspension culture
      were cocultivated with bacteria which were derived from the nopaline strain C58
      of Agrobacterium tumefaciens. When the bacteria carried an oncogenic Ti-plasmid,
      about 5% of the surviving protoplasts were able to form calli on hormone-free
      agar in contrast to controls, where bacteria without Ti-plasmid were applied, and
      where no calli were formed. After isolation of DNA from hormone-independently
      growing cells further evidence for transformation was obtained by hybridization
      to Ti-plasmid specific RNA and by rescue of a segment with a bacterial resistance
      gene which had been inserted before into the T-DNA. Transfer of T-DNA harboring a
      neomycin-resistance gene activated by the nos-promoter resulted in calli growing
      on kanamycin. Verification of segments located at the left and the right part of
      the T-DNA indicated the presence of its entire length in transformed soybean
      cells. Expression of T-DNA genes was measured by the assay of nopaline-synthase.
      Cells cultured on agar had a much higher level of nopaline-synthase than fast
      growing cells in suspension culture. Transferring them to agar or treatment with
      azacytidine strongly increased synthesis of nopaline-synthase indicating a
      reversible repression presumably via a methylation mechanism. 

PMID- 24276904
TI  - Partial purification of plant transcription factors. I. Initiation.
AB  - Crude plant cell protein extracts prepared from wheat germ are inactive for in
      vitro transcription by RNA polymerase II. These extracts do, however, have
      correct initiation of transcription by RNA polymerase II. Initiation is monitored
      by measuring the formation of transcription complexes in vitro. A nuclear extract
      produces more initiation events than a whole cell extract or a cytosol extract.
      Some factors necessary for initiation can be separated from other proteins,
      including inhibitors, by ion exchange column chromatography. One specific
      fraction is sufficient for the formation of transcription complexes and several
      other fractions may be stimulatory or accessory factors. 

PMID- 24276905
TI  - Partial purification of plant transcription factors. II. An in vitro
      transcription system is inefficient.
AB  - Crude wheat germ nuclear extracts contain many inhibitors of transcription which
      need to be removed before an active system can be developed. Using ion exchange
      column chromatography to resolve RNA polymerase II transcription components we
      can identify at least four fractions required for transcription by their ability
      to interact with, or substitute for, particular HeLa fractions. Inhibitors can be
      removed by a second or third chromatographic process applied to each fraction.
      Two plant fractions can each effectively replace the corresponding fraction in a
      HeLa transcription system, and the wheat fractions can work together and replace
      two HeLa fractions. These plant factors chromatograph identically to HeLa factors
      on ion exchange columns. The third fraction does not fully substitute for the
      corresponding HeLa fraction, but can complement this HeLa fraction when both are
      added at half-optimal levels. An in vitro plant system consisting of four plant
      chromatographic fractions will selectively transcribe a gene, but only at very
      low efficiency. The apparent block to greater efficiency is in elongation of the
      RNA past the 20-30n size. 

PMID- 24276906
TI  - Rhizobium nod genes are involved in the induction of two early nodulin genes in
      Vicia sativa root nodules.
AB  - Nodulin gene expresison was studied in Vicia sativa (common vetch) root nodules
      induced by several Rhizobium and Agrobacterium strains. An Agrobacterium
      transconjugant containing a R. leguminosarum symplasmid instead of its Ti
      plasmid, that was previously shown to form "empty" nodules on pea, induced
      nodules on Vicia roots in which nodule cells were infected with bacteria. In the
      Vicia nodules induced by this transconjugant, two so-called early nodulin genes
      were found to be expressed, whereas in the nodules formed on pea the expression
      of only one early nodulin gene was detected. In both cases the majority of the
      nodulin genes was not expressed.Apparently, an intracellular location of the
      bacteria is not sufficient for the induction of the majority of the nodulin
      genes. All nodulin genes were expressed in nodules induced by cured Rhizobium
      strains containing cosmid clones that have a 10 kb nod region of the sym-plasmid
      in common. Since in tumours no nodulin gene expression was found at all, the
      Agrobacterium chromosome does not contribute to the induction of nodulin genes.
      Therefore it is concluded that the signal for the induction of the expression of
      the two Vicia early nodulin genes is encoded by the nod-region, and the signal
      involved in the induction of all other nodulin genes has to be located outside
      the sym-plasmid, on the Rhizobium chromosome. The apparent difference in early
      nodulin gene expression between pea and Vicia is discussed in the light of the
      usefulness of Agrobacterium transconjugants in the study of nodulin gene
      expression. 

PMID- 24276907
TI  - A pilot randomized trial of community-based parent training for immigrant Latina
      mothers.
AB  - This paper reports on the development and piloting of the Madres a Madres
      (Mothers to Mothers) program, a new, community-based parent training program
      designed for immigrant Latina mothers and their children. Promotoras, or female
      community health workers of Latina background, delivered the program in a home
      visitation format. A total of 194 mothers and 194 focal children (87 male, 107
      female) ages 7-12 were randomized to the intervention (113 mother-child dyads) or
      wait-list control condition (81 mother-child dyads) over the study period.
      Outcomes of interest were mother-reported parenting skills, broad family
      functioning, and child externalizing and internalizing behaviors. Data collection
      occurred at pretest, 3-month posttest, and 9-month follow-up periods. Multilevel
      growth models revealed increases in intervention mothers' reported parenting
      skills, family support, and family organization, and reductions in child
      internalizing behavior from pretest to follow-up, relative to the control
      condition. Outcomes did not vary by focal child age, gender, nativity status, or
      mother acculturative status (years in the United States). Findings are discussed
      in the context of future directions for research on the Madres a Madres program
      and on the implementation and dissemination of empirically-supported parent
      training practices to culturally diverse families. 

PMID- 24276908
TI  - Mathematics, mythology, and mysticism.

PMID- 24276909
TI  - Development of a model for spiritual assessment and intervention.
AB  - A multidisciplinary model for making spiritual assessments and interventions is
      described. The practitioner bases these assessments and interventions upon
      knowledge gained from philosophy, theology, physiology, psychology, and
      sociology. Specific assessments are made in the areas of spiritual development
      and seven practical dimensions of spiritual care. The patient's life experiences,
      events, and questions shape the nature of spiritual care as the practitioner
      works toward assisting the patient to maintain or expand the level of spiritual
      functioning. 

PMID- 24276910
TI  - The final portrait of Christ.
AB  - Artistic presentations of Jesus are as numerous and varied as the artists who
      created them. Whether on canvas or in music, Jesus has been portrayed as a
      redeemer, revolutionary, teacher, and clown. While some people are inspired by a
      particular presentation of Jesus, others are angered and incensed at what they
      perceive to be blasphemous. An example of the latter is Martin Scorsese's film,
      "The Last Temptation of Christ." This article examines why people responded so
      negatively to this and other artistic presentations of Jesus. It suggests they
      have failed to recognize how the portrayal reflects a personal experience of the
      artist and is not meant to be a final portrait of Christ. And on a more
      unconscious level, these works of art evoke feelings within people which they
      fear to acknowledge and which they escape by condemning the work. 

PMID- 24276911
TI  - Fundamentalist religion and its effect on mental health.
AB  - The national self-help group, Fundamentalists Anonymous (F.A.), has focused
      attention upon mental problems that may be caused or exacerbated by authoritarian
      religion. In this article we outline assertions about the mental problems caused
      by membership in fundamentalist religion, illustrate these with two case
      histories, briefly discuss intervention strategies, and describe conceptual and
      empirical issues. While former members have presented problems severe enough to
      warrant professional treatment, a causal link between their symptoms and their
      religious membership has not yet been established, because there is little
      empirical work on the subject. 

PMID- 24276912
TI  - Socrates and psychotherapy.
AB  - This article examines the basic philosophical ideas of Socrates and how these
      ideas form a basic part of the philosophical foundation of psychotherapy. His
      influence is analyzed by observing how Kierkegaard and Nietzsche view his
      contribution. The controversial thesis of I.F. Stone's recent book,The Trial of
      Socrates, is used to re-examine the man and his philosophy. 

PMID- 24276913
TI  - Death, sin, and God's judgment.
AB  - Grief is difficult for everyone, including the professional. And yet resolving
      grief is necessary for life to be comfortable and productive. This paper looks at
      the story of a young man and how unresolved grief, inappropriate guilt, and
      uncontrollable despair colored every phase of his life. It also demonstrates the
      tragedy when grief is allowed to remain in denial and resolution comes too late. 

PMID- 24276914
TI  - Picturing god.
AB  - All perception and judgment are to some extent the reflection of who we are. Our
      picture of God, too, is a product of the cave into which we were born.
      Acknowledging this is an antidote to one form of idolatry-the worship of our
      symbols for God. This confession that our pictures never perfectly reflect God
      does not mean, however, that we cannot give reasons for thinking that one picture
      of God is more adequate than another. The paper attempts to demonstrate this by
      reference to contrasting pictures of God analyzed by the process thinker Charles
      Hartshorne. 

PMID- 24276915
TI  - Our existential dilemma:Bor orBe'er.
AB  - An evaluation is made of the choices available to individuals in dealing with
      their essential alone-ness, the existential dilemma; and a parallel is drawn
      between these choices and flowing and stagnant waters, as interpreted by
      traditional sources. 

PMID- 24276916
TI  - Integrated use of residues from olive mill and winery for lipase production by
      solid state fermentation with Aspergillus sp.
AB  - Two-phase olive mill waste (TPOMW) is presently the major waste produced by the
      olive mill industry. This waste has potential to be used as substrate for solid
      state fermentation (SSF) despite of its high concentration of phenolic compounds
      and low nitrogen content. In this work, it is demonstrated that mixtures of TPOMW
      with winery wastes support the production of lipase by Aspergillus spp. By agar
      plate screening, Aspergillus niger MUM 03.58, Aspergillus ibericus MUM 03.49, and
      Aspergillus uvarum MUM 08.01 were chosen for lipase production by SSF. Plackett
      Burman experimental design was employed to evaluate the effect of substrate
      composition and time on lipase production. The highest amounts of lipase were
      produced by A. ibericus on a mixture of TPOMW, urea, and exhausted grape mark
      (EGM). Urea was found to be the most influent factor for the lipase production.
      Further optimization of lipase production by A. ibericus using a full factorial
      design (3(2)) conducted to optimal conditions of substrate composition (0.073 g
      urea/g and 25 % of EGM) achieve 18.67 U/g of lipolytic activity.

PMID- 24276917
TI  - Regorafenib: a review of its use in previously treated patients with progressive
      metastatic colorectal cancer.
AB  - Regorafenib (Stivarga) is an inhibitor of multiple protein kinases, including
      those involved in oncogenesis, tumour angiogenesis and maintenance of the tumour
      microenvironment. The drug is approved as monotherapy for the treatment of
      metastatic colorectal cancer (mCRC) in patients who have previously received all
      standard systemic anticancer treatments (US, EU and Canada) or in patients with
      unresectable, advanced or recurrent colorectal cancer (Japan). In the randomized,
      controlled COloRectal cancer treated with REgorafenib or plaCebo after failure of
      standard Therapy (CORRECT) trial, regorafenib 160 mg once daily for the first 3
      weeks of each 4-week cycle plus best supportive care (BSC) was associated with a
      significantly longer median overall survival than placebo plus BSC in patients
      with previously treated, progressive mCRC. The drug was also associated with
      significantly longer progression-free survival and better disease control rates
      than placebo, although objective response rates were similar in both treatment
      groups. Regorafenib did not appear to compromise health-related quality of life
      over the study duration and had a generally acceptable tolerability profile. The
      introduction of regorafenib expands the currently limited range of effective
      treatment options in patients with previously treated, progressive mCRC.

PMID- 24276918
TI  - The role of Somatic embryogenesis receptor-like kinase 1 in controlling pollen
      production of the Gossypium anther.
AB  - In flowering plants, male gametophytes are generated in anthers from
      microsporocytes. However, more evidence is needed to reveal the genetic
      mechanisms which regulate the differentiation and interaction of these highly
      specialized cells in anthers. Here we report the characterization of a series of
      male-sterile cotton (Gossypium hirsutum) mutants, including mutants with normal
      fertility, semi-sterility and complete sterility. These mutants are forms of
      transgenic cotton containing RNAi vectors with partial cDNA fragments of GhSERK1.
      The GhSERK1 gene encodes a putative leucine-rich repeat receptor protein kinase
      (LRR-RLK), and generally has 11 domains. In previous research, we found plants
      containing GhSERK1 produce an abundance of male reproductive tissue. In this
      paper, three RNAi constructs were designed separately to analyze its function in
      anther. After the three RNAi vectors were transformed into the cotton, transgenic
      plants with the specialized fragment exhibited normal fertility or the pollen
      energy decreased slightly, as ones with the homologous fragments exhibited
      various degrees of male sterility with different expression levels of GhSERK1
      mRNA. In conclusion, for the transgenic plants with conserved fragments, lower
      expression levels of GhSERK1 mRNA were in transgenic plants, and a higher degree
      of male sterility was observed. Taking together, these findings demonstrate the
      GhSERK1 gene has a role in the development of anthers, especially in the
      formation of pollen grains. Also, we infer there must be another homolog of
      GhSERK1 in cotton, and both of GhSERK1 and its homolog function redundantly as
      important control points in controlling anther pollen production.

PMID- 24276919
TI  - Inheritance of glutenin protein subunits of wheat.
AB  - The inheritance of the high-molecular-weight (HMW) glutenin protein subunits in
      hexaploid wheat has been investigated by using sodium dodecyl sulphate
      polyacrylamide gel electrophoresis to examine the segregation of these subunits
      in 496 test-cross seeds. The parents of the f1 hybrid were chosen so that the
      test-cross seeds segregated for all the HMW glutenin bands. Two glutenin subunits
      from one parent, believed to be controlled by genes on chromosome 1D, segregated
      as alternatives to two glutenin subunits from the other parent, a result that
      supports the assumption that these subunits are controlled by allelic genes at
      each of two loci that are very closely linked. Similar results were obtained for
      glutenin subunits believed to be controlled by chromosome IB, which suggests that
      these subunits are controlled also by allelic genes at each of two loci that are
      very closely linked. A single glutenin subunit band, believed to be controlled by
      chromosome 1A, segregated as an alternative to a single glutenin band from the
      other parent, except that one seed did not possess either band. It was concluded
      that these bands are controlled either by allelic genes or by nonallelic genes
      that are very closely linked. 

PMID- 24276920
TI  - Combining ability analysis over environments in diallel crosses of linseed (Linum
      usitatissimum L.).
AB  - This paper reports on combining ability studies for yield and its component
      traits in diallel crosses involving ten ecogeographically and genetically diverse
      linseed (Linum usitatissimum L.) cultivars in the F2 generation over three
      locations. The general combining ability (GCA) and specific combining ability
      (SCA) mean squares were significant at all three locations for all traits.
      Combined analysis over locations showed the same trend of significance. The ratio
      of GCA to SCA mean squares was significant for all the traits in individual
      location analysis as well as in combined analysis. This indicated the predominant
      role of additive gene effects in the inheritance of these characters. The GCA
      mean squares were several times larger than SCA mean squares for all the traits,
      indicating the presence of considerable magnitude of additive genetic variance
      and the additive x additive components of the epistatic variance. Consequently,
      effective selection should be possible within these F2 populations for all
      characters. Significant genotype-location and GCA-location interactions indicated
      that more than one test location is required to obtain reliable information. The
      inexpensive and reliable procedure used for making the choice of parents was the
      determination of breeding values of the parents on the relative performance of
      their F2 progeny bulks. 

PMID- 24276921
TI  - Plantlet regeneration from mesophyll protoplasts of Digitalis lanata Ehrh.
AB  - Protoplasts were isolated from the mesophyll of Digitalis lanata enzymatically
      and cultured in a liquid regeneration medium (D2a). Protoplast division occurred
      at a rate of approximately 30%. Mature cell colonies were transferred onto agar
      medium (D2b)where they developed into cell clusters with a diameter of about 4-5
      mm. After transfer onto MS medium, these calli differentiated leaves and shoots
      which could be rooted on MS medium containing a low hormone concentration. 

PMID- 24276922
TI  - Intergeneric hybrids between Triticum crassum and Hordeum vulgare.
AB  - Intergeneric hybrids between Triticum crassum (2n=6x=42) and Hordeum vulgare cv.
      'Bomi' were obtained at a frequency of 15% of pollinated florets. Meiotic
      chromosome pairing in the hybrids was not different from that observed in a
      polyhaploid of T. crassum indicating negligible pairing between chromosomes of
      the two species and secondly that the genome of H. vulgare had no effect on
      intergenomic pairing in T. crassum. 

PMID- 24276923
TI  - Tissue culture in Haworthia : Part 4: genetic characterization of plants
      regenerated from callus.
AB  - Plants regenerated on two different media (NK and I) from the calluses of simple
      or cloned subcultures, which were originated from a single stock callus of
      Haworthia setata derived from its flower bud, were observed for eight characters,
      i.e., somatic chromosome number in root tips, growth vigor, leaf shape, leaf
      color, number of stomata per unit leaf area, esterase zymogram, chromosome
      association at meiotic metaphase I in pollen mother cells, and pollen fertility.
      From these regenerates plants with different characters from those of the
      parental plant were obtained. With regards to chromosomal aberrations,
      tetraploids, aneuploids, plants with a part of the chromosome segment deleted,
      with reciprocal and non-reciprocal translocations, or with paracentric inversions
      and those showing sub-chromatid aberrations at meiosis were obtained. The NK
      medium tended to regenerate more tetraploids and less plants carrying
      translocation than the I medium.Chromosome variabilities in somatic cells of the
      regenerates correlated with those of the calluses, from which they regenerated,
      while they did not correlate with either the meiotic irregularities (chromosome
      association at MI) or pollen fertility of the regenerates. From these facts, it
      was concluded that a rather large number of callus cells participate in the
      regeneration of an individual plant, although, however, only a few limited types
      of the cells form its germ line.Polyploidy affected growth vigor, leaf shape,
      stomata number and chromosome association at MI, but its effects were not
      detected on other characters. Chromosomal aberrations at the diploid level
      produced no clear changes in the regenerate's phenotype except in meiotic
      chromosome configuration and pollen fertility.Most chromosomal variants obtained
      in the present study are already reported in plants collected from wild
      populations, but plants with the deletion of a whole chromosome (karyotype 7L+6S)
      or chromosome segment (7L+1M+6S and 14L+2M+12S) have never been reported: this
      fact suggests that tissue culture is a powerful tool for producing plants with
      novel karyotypes. 

PMID- 24276924
TI  - Effects of the Nicotiana debneyi black root rot resistance factor on agronomic
      and chemical traits in burley tobacco.
AB  - Lines isogenic or near isogenic for traits other than resistance to black root
      rot from Nicotiana debneyi were developed in eight cultivar backgrounds of burley
      tobacco (N. tabacum L.). For each cultivar background, a resistant and
      susceptible selection from the seventh backcross generation plus the recurrent
      parental cultivar were evaluated for ten agronomic and chemical traits. Resistant
      selections were statistically different from the susceptible entries for days to
      flower, total nitrogen content, and total alkaloid content. Also, resistant
      selections were consistently lower in yield, but the differences were
      statistically nonsignificant. Resistant selections were also taller in three
      families and in two families the resistant selections had wider leaves. Linkage
      of genetic material from N. debneyi with the resistance factor was suggested as
      the possible reason for differences between resistant and susceptible selections.

PMID- 24276925
TI  - Genetic variation and climatic selection in the lizard Agama stellio in Israel
      and Sinai.
AB  - Allozymic variation in proteins encoded by 25 loci was analyzed
      electrophoretically in 242 adult specimens representing nine populations of the
      Levantine lizard, Agama stellio, comprising two subspecies: the Mediterranean A.
      stellio subsp., and the desert-inhabiting A. stellio brachydactyla from the Negev
      and Sinai. Likewise, four body traits were measured in the same populations. The
      nine populations were sampled along a general southward transect of increasing
      aridity. Agama stellio is above average in both polymorphism, P, and
      heterozygosity, H, as compared to other reptiles and vertebrates in general,
      displaying levels of genetic variation characterizing habitat generalist
      vertebrates. In the populations studied no fixation of alternative alleles was
      found in any of the 25 loci: rather the commonest allele was either fixed or
      predominated in 23 of 25 loci examined. Eleven loci (44%) were monomorphic in all
      nine populations. However, of the remaining 14 polymorphic loci, eight were
      strongly polymorphic displaying distinct genetic differentiation between
      populations. Genetic diversity (indexed by P and H) displayed geographic
      variation and was slightly higher in A.s. brachydactyla than in A. stellio subsp.
      Nevertheless, genic similarity between populations was high. A statistically
      significant amount of morphological variation between localities was found for
      all body characters. In general, body size increased southwards and eastwards
      with aridity.Selection at some loci is suggested by significant deviation from
      Hardy-Weinberg expectations and possibly by excess heterogeneity of effective
      inbreeding coefficients, Fe. Furthermore, allozymic variation at seven loci (Ldh
      1, Idh-1, 6-Pgd-1, Aat-1, Pgm-2, Pept-1, and Trf) and geographic variation in
      body size and weight were significantly correlated with, and predictable by,
      climatic variables, primarily by water availability and secondarily by
      temperature. Finally, allozymic and morphological variations were partly
      correlated.The spatial patterns and ecological correlates of genic and
      morphological variations in Agama stellio in Israel and Sinai suggest that at
      least some proteins and body size differentiate geographically and appear to be
      adaptive, presumably with respect to factors affecting the availability of water.

PMID- 24276926
TI  - Telo aneuploids in pearl millet.
AB  - Nomenclature and chromosome constitution for twenty different aneuploids with
      telocentrics in Pennisetum typhoides are presented. 

PMID- 24276927
TI  - Mutations in rDNA. 1. Dependence of chromosome mutation induction on positions
      and activity of nucleolus organizer regions.
AB  - Studies on chromatid aberration induction in NORs of standard and reconstructed
      karyotypes, as well as in the single translocation lines of barley, indicate a
      correlation between synthetic activity (transcription) of rDNA and frequency of
      chromosome mutations induced by HU. Experimental evidence in favour of this
      inference arises from analyzing karyotypes with NORs located at their original
      sites and karyotypes with NORs translocated from their original sites. The close
      correlation between the different rate of synthetic activity (transcription) in
      nucleolus formation and the comparable range of variation in aberration
      involvement of NORs observed in translocation lines are discussed. 

PMID- 24276929
TI  - The somatic symptom scale-8 (SSS-8): a brief measure of somatic symptom burden.
AB  - IMPORTANCE: Somatic symptoms are the core features of many medical diseases, and
      they are used to evaluate the severity and course of illness. The 8-item Somatic
      Symptom Scale (SSS-8) was recently developed as a brief, patient-reported outcome
      measure of somatic symptom burden, but its reliability, validity, and usefulness
      have not yet been tested. OBJECTIVE: To investigate the reliability, validity,
      and severity categories as well as the reference scores of the SSS-8. DESIGN,
      SETTING, AND PARTICIPANTS: A national, representative general-population survey
      was performed between June 15, 2012, and July 15, 2012, in Germany, including
      2510 individuals older than 13 years. MAIN OUTCOMES AND MEASURES: The SSS-8 mean
      (SD), item-total correlations, Cronbach alpha, factor structure, associations
      with measures of construct validity (Patient Health Questionnaire-2 depression
      scale, Generalized Anxiety Disorder-2 scale, visual analog scale for general
      health status, 12-month health care use), severity categories, and percentile
      rank reference scores. RESULTS: The SSS-8 had excellent item characteristics and
      good reliability (Cronbach alpha = 0.81). The factor structure reflects
      gastrointestinal, pain, fatigue, and cardiopulmonary aspects of the general
      somatic symptom burden. Somatic symptom burden as measured by the SSS-8 was
      significantly associated with depression (r = 0.57 [95% CI, 0.54 to 0.60]),
      anxiety (r = 0.55 [95% CI, 0.52 to 0.58]), general health status (r = -0.24 [95%
      CI, -0.28 to -0.20]), and health care use (incidence rate ratio, 1.12 [95% CI,
      1.10 to 1.14]). The SSS-8 severity categories were calculated in accordance with
      percentile ranks: no to minimal (0-3 points), low (4-7 points), medium (8-11
      points), high (12-15 points), and very high (16-32 points) somatic symptom
      burden. For every SSS-8 severity category increase, there was a 53% (95% CI, 44%
      to 63%) increase in health care visits. CONCLUSIONS AND RELEVANCE: The SSS-8 is a
      reliable and valid self-report measure of somatic symptom burden. Cutoff scores
      identify individuals with low, medium, high, and very high somatic symptom
      burden.

PMID- 24276928
TI  - Chronic granulomatous disease: two decades of experience from a tertiary care
      centre in North West India.
AB  - Chronic granulomatous disease (CGD) results from an inherited defect in the
      phagocytic cells of the immune system. It is a genetically heterogenous disease
      caused by defects in one of the five major subunits of the nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from
      India on CGD. We herein describe the clinical features in 17 children with CGD
      from a single tertiary referral center in India. A detailed analysis of the
      clinical features, laboratory investigations and outcome of 17 children 7 with X
      linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of
      CGD was based on an abnormal granulocyte oxidative burst evaluated by either
      Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123
      assay or both. The molecular diagnosis was confirmed by genetic mutation analysis
      in 13 cases. The mean age at diagnosis and the age at onset of symptoms was
      significantly lower in children diagnosed with XL- CGD compared those with AR
      disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1
      gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the
      disease was much worse in children diagnosed with X-linked form of disease
      compared to AR forms of the disease; 4/7 (57%) children with X-CGD were dead at
      the time of data analysis. This is one of the largest series on chronic
      granulomatous disease from any developing country.

PMID- 24276930
TI  - The immuno-histochemical localization of lectin in pea seeds (Pisum sativum L.).
AB  - The lectin from the garden pea (Pisum sativum L.) has been localized at the
      ultrastructural level by the unlabeled peroxidase-antiperoxidase procedure of
      L.A. Sternberger et al. (1970, J. Histochem. Cytochem 18, 315-333) in 24 h
      imbibed seeds. Upon examination by light microscopy and transmission electron
      microscopy, the lectin was only found in the protein bodies of cotyledons and
      embryo axis. Cell walls as well as membraneous fractions were completely devoid
      of lectin. These results are discussed in relation to the possible physiological
      function of seed lectins. 

PMID- 24276931
TI  - Cytokinin metabolism in Phaseolus vulgaris L. : Identification of endogenous
      cytokinins and metabolism of [8-(14)C]dihydrozeatin in stems of decapitated
      plants.
AB  - The major cytokinins in stems of decapitated, disbudded bean plants have been
      identified by enzymic degradation, Sephadex LH20 and reversed phase high
      performance liquid chromatography, and by combined gas chromatography-mass
      spectrometry as 6-(4-hydroxy-3-methylbut-trans-2-enylamino)-9-beta-D
      ribofuranosylpurine (zeatin riboside), 6-(4-hydroxy-3-methylbutylamino)-9-beta-D
      ribofuranosylpurine (dihydrozeatin riboside), and the 5'-phosphates of these
      compounds (zeatin ribotide and dihydrozeatin ribotide). Minor cytokinins in this
      tissue were tentatively identified as dihydrozeatin-O-beta-D-glucoside and zeatin
      ribotide-O-beta-D-glucoside. [8-(14)C-]Dihydrozeatin appeared to be rapidly
      metabolized to dihydrozeatin ribotide when supplied to segments of stems from
      decapitated plants. These results are discussed in relation to the metabolism and
      distribution of cytokinins in the whole plant. 

PMID- 24276932
TI  - Induction of gravity-dependent plasmatic responses in root statocytes by short
      time contact between amyloplasts and the distal endoplasmic reticulum complex.
AB  - Statocytes from roots of Lepidium sativum L., which developed after a 2-min
      soaking on a horizontal clinostat (2 rotations per min) for 44 h, exhibit the
      same polarity as in vertically grown roots, as indicated by a complex of
      endoplasmic reticulum (ER) cisternae at the distal cell pole. Amyloplasts are
      distributed randomly. The kinetics of graviresponse (=curvature) of such roots
      are identical to those of normally grown roots. Ten-minute exposure of the root,
      after 24 h development on the clinostat with gravity acting towards the root's
      basis (inversion), induces no changes in statocyte ultrastructure. However,
      corresponding exposure in normal orientation leads to subsequent disintegration
      of the distal ER complex, loss of amyloplast starch, confluence of lipid
      droplets, and an increase of the lytic compartment. These ultrastructural events
      thus appear to be induced by a physical contact - however short - between
      amyloplasts and the distal ER complex. 

PMID- 24276933
TI  - Cyclic and noncyclic photophosphorylation during the ontogenesis of high-light
      and low-light leaves of Sinapis alba.
AB  - Noncyclic electron transport to ferricyanide and photophosphorylation as well as
      the methylviologen mediated aerobic and anaerobic photophosphorylation with
      dichlorophenolindophenol-ascorbate as the electron donor of photosystem I were
      measured during the development of high-light and low-light adapted leaves of
      Sinapis alba. Anaerobic methylviologen-catalyzed phosphorylation is more than
      twice as high as aerobic phosphorylation. The difference between the rates of
      aerobic and anaerobic phosphorylation is sensitive to dibromothymoquinone. Thus,
      under anaerobic conditions, methylviologen mediates a cyclic phosphorylation
      including plastoquinone. All photochemical activities of high-light chloroplasts
      are about twice as high as that of low-light chloroplasts and show a permanent
      decline with increasing plant age. The lower activities of low-light chloroplasts
      correlate with a decrease of electron transport components, such as cytochrome f.
      This indicates that the number of electron transport chains is decreased under
      low-light conditions and more chlorophyll molecules interact with one
      electrontransport chain. 

PMID- 24276934
TI  - Hydrogen evolution by photobleached Anabaena cylindrica.
AB  - We have studied the evolution of hydrogen by photobleached filaments of the
      heterocystous bluegreen alga Anabaena cylindrica. The photobleached cells became
      orange-yellow due to the heavy accumulation of carotenoids. We found that the
      yellow filaments produced much larger amounts of hydrogen than the normal, green
      ones, while the nitrogenase activity responsible for hydrogen evolution increased
      to a lesser extent. We suggest that a reversible hydrogenase activity induced in
      photobleached filaments is responsible for the excess amount of hydrogen. 3
      (3',4'-dichlorophenyl)-1,1-dimethyl urea (DCMU) inhibits the hydrogen evolution
      of the yellow filaments which produce much more oxygen and fix less CO2 than the
      green filaments. Therefore we consider the water to be a possible electron source
      for this hydrogenase. The low efficiency of light energy conversion (0.3%) in
      nitrogenase-catalyzed H2 evolution (Laczko, 1980 Z. Pflanzenphysiol. 100, 241
      245) is increased to 1.5-2% by the appearance of the reversible hydrogenase
      activity. 

PMID- 24276935
TI  - Promotion of stomatal opening in detached epidermis of Kalanchoe daigremontiana
      Hamet et Perr. by natural and synthetic cytokinins.
AB  - The cytokinins kinetin and zeatin increased stomatal opening at 15 degrees C in
      the dark by up to 50% in detached epidermis of the CAM plant Kalanchoe
      daigremontiana. Stomata opened maximally following incubation with 10 mmol m(-3)
      cytokinin. This study extends the range of species in which exogenous cytokinins
      promote stomatal opening. 

PMID- 24276936
TI  - Radioimmunoassay for pmol-quantities of indole-3-acetic acid for use with highly
      stable [(125)I]- and [ (3)H]IAA derivatives as radiotracers.
AB  - A radioimmunoassay for the detection of as little as 0.5-1 pmol indole-3-acetic
      acid (IAA) in unpurified or partially purified plant extracts is described. The
      assay makes use of either IAA[(125)I]tyrosine methyl ester or [(3)H]IAA methyl
      ester as radioactive antigens and IAA methyl ester as the assay standard
      (measuring range: 1-200 pmol). Levels of extractable IAA in a number of
      biological samples have been estimated. 

PMID- 24276937
TI  - Phytohormones in the formation of crown gall tumors.
AB  - Crown gall tumors were initiated in a variety of plant species by infection with
      Agrobacterium tumefaciens strain B6 and the concomitant changes in the tissue
      levels of phytohormones, mainly indole-3-acetic acid (IAA) and cytokinins, were
      analyzed. A comparison was made of these hormones with those produced by virulent
      and avirulent strains of the bacterium in liquid culture and with those of
      bacteria-free crown gall callus cultures. Specific radioimmunoassays were
      employed for hormone determinations. An assay for the quantitation of femto-mol
      amounts of isopentenyladenosine and related cytokinins was newly developed and is
      described in detail. The results can be summarized as follows: Virulence in
      strain B 6 is associated with the ability to release trans-zeatin and increased
      amounts of IAA into the surrounding environment. In many, but not all plants
      analyzed, the development of crown gall tumors is also associated with a sharp
      rise in the levels of trans-zeatin-type zytokinins and IAA (e.g., Euphorbia
      lathyris, Catharanthus roseus). Crown gall calli growing on hormone-free media
      varied greatly in their cytokinin levels. In a culture of Nicotiana tabacum, both
      trans-zeatin and isopentenyladenine or related cytokinins were not detected.
      Thus, tumor growth cannot be explained on the basis of elevated levels of IAA
      and/or cytokinins alone. 

PMID- 24276938
TI  - The role of ferritin in developing primary bean leaves under various light
      conditions.
AB  - Ferritin and ferritin-iron in the primary leaves of Phaseolus vulgaris L. were
      determined during growth in the dark, in the light, and during de-etiolation. The
      ratio ferritin protein/total protein appeared to be rather constant. In dark
      grown leaves maximally 50% of the total extractable iron was found to be present
      in ferritin. This percentage was lower in deetiolating and light-grown leaves. In
      ten-day-old green leaves no ferritin-iron could be measured. The translocation of
      iron from cotyledons to the developing plant appears to be related to the need
      for iron in the leaves. These results suggest that ferritin acts as a buffer
      molecule for iron in plants. 

PMID- 24276939
TI  - Water relations of growing pea epicotyl segments.
AB  - The water relations of growing epicotyl segments of pea (Pisum sativum L.) were
      studied using the miniaturized pressure probe. For epidermal cells stationary
      turgor pressures of P=5 to 9 bar and half-times of water exchange of individual
      cells T 1/2=1 to 27 s were found. The volumetric clastic modulus (E) of epidermal
      cells varied from 12 to 200 bar and the hydraulic conductivity, Lp=0.2 to 2.10(
      6) cm s(-1) bar(-1). For cortical cells P=5 to 11 bar, T 1/2=0.3 to 1 s, Lp=0.4
      to 9.10(-5) cm s(-1) bar(-1) and E=6 to 215 bar. The T 1/2 of cortical cells was
      extremely low and the Lp rather high as compared to other higher plant cells. The
      T 1/2-values of cortical cells were sometimes observed to change from short to
      substantially longer values (T 1/2=3 to 20 s). Both short and long pressure
      relaxations showed all the characteristics of non-artifactual curves. The change
      is apparently due to an increase in Lp and not E, but the reason for the change
      in cell permeability to water is not known.In osmotic exchange experiments on
      peeled segments using solutions of different solutes, the half-time of osmotic
      water exchange for the whole segment was approximately 60 s. Water exchange
      occurred too quickly to be rate controlled by solute diffusion in the wall space.
      The data suggest that the short T 1/2-values in the cortical cells are the
      physiologically relevant ones for the intact tissue and that a considerable
      component of water transport occurs in the cell-to-cell pathway, although
      unstirred layer effects at the boundary between the segment and solution may
      influence the measured half-time. Using the theory of Molz and Boyer (1978, Plant
      Physiol. 62, 423-429), the gradient in water potential necessary to maintain the
      uptake of water for cell enlargement can be calculated from the measured
      diffusivities to be approximately 0.2 and 1 bar for growth rates of 1% h(-1) and
      5% h(-1), respectively. Thus, although the T 1/2-values are short and Lp rather
      high, there may be a significant osmotic disequilibrium in the most rapidly
      growing tissue and as a consequence the influence of water transport on the
      growth rate cannot be excluded. 

PMID- 24276940
TI  - Mode of glucan degradation by purified phosphorylase forms from spinach leaves.
AB  - The glucan specifity of the purified chloroplast and non-chloroplast forms of
      alpha-1,4-glucan phosphorylase (EC 2.4.1.1) from spinach leaves (Steup and E.
      Latzko (1979), Planta 145, 69-75) was investigated. Phosphorolysis by the two
      enzymes was studied using a series of linear maltodextrins (degree of
      polymerization ?11), amylose, amylopectin, starch, and glycogen as substrates.
      For all unbranched glucans (amylose and maltodextrins G5-G11), the chloroplast
      phosphorylase had a 7-10-fold higher apparent affinity (determined by initial
      velocity measurements) than the non-chloroplast phosphorylase form. For both
      enzyme forms, the minimum chain length required for a significant rate of
      phosphorolysis was five glucose units. Likewise, phosphorolysis ceased when the
      maltodextrin was converted to maltotetraose. With the chloroplast phosphorylase,
      maltotetraose was a linear competitive inhibitor with respect to amylose or
      starch (K i-0.1 mmol 1(-1)); the inhibition by maltotetraose was less pronounced
      with the non-chloroplast enzyme. In contrast to unbranched glucans, the non
      chloroplast phosphorylase exhibited a 40-, 50-, and 300-fold higher apparent
      affinity for amylopectin, starch, and glycogen, respectively, than the
      chloroplast enzyme. With respect to these kinetic properties the chloroplast
      phosphorylase resembled the type of "maltodextrin phosphorylase". 

PMID- 24276941
TI  - Sexual agglutination factor from Chlamydomonas eugametos.
AB  - Chlamydomonas eugametos gametes can sexually agglutinate via their flagellar
      surfaces whereas vegetative cells cannot. Therefore, flagellar glycoproteins,
      present in gamete cells but absent from vegetative cells, were investigated as
      prospective mt (-)agglutination factors. They were identified as periodic acid
      Schiff (PAS) stained bands separated in sodium dodecyl sulphate-polyacrylamide
      electrophoresis gels. Gamete-specific bands were determined by comparison with
      equivalent gels of vegetative flagella and by immunological techniques using
      antisera raised against isolated mt (-) gamete flagella. Four high molecular
      weight flagellar glycoproteins proved to be gamete specific (PAS-1.2, PAS-1.3,
      PAS-3 and PAS-4). They were extracted from flagella by 3 M guanidine thiocyanate,
      separated in a column of Sepharose 2B, and tested for in vitro agglutination
      activity on mt (+) gametes. A single peak of activity was found to be correlated
      with the presence of the PAS-1.2 band. It is shown that mt (-) agglutination
      activity is related to the concentration of this glycoprotein in flagellar
      membranes. 

PMID- 24276942
TI  - Separation and characteristics of galactose-1-phosphate and glucose-1-phosphate
      uridyltransferase from fruit peduncles of cucumber.
AB  - Galactose-1-phosphate uridyltransferase (EC 2.7.7.10), responsible for the
      conversion of galactose-1-phosphate (Gal-1-P) to uridine diphosphate galactose
      (UDPgal) was examined in fruit peduncles of Cucumis sativus L. Two
      uridyltransferases (pyrophosphorylases), from I and II, were partially purified
      and resolved on a diethylamino-ethyl-cellulose column. Form I can utilize glucose
      1-phosphate (Glc-1-P), while form II can utilize either Gal-1-P or Glc-1-P, with
      a preference for Gal-1-P. Form I was more heat stable than form II. Both Glc-1-P
      and Gal-1-P activities of form II were inactivated at the same rate by heating.
      The finding of a uridyltransferase with preference for Gal-1-P indicates that
      cucumber may have a Gal-1-P uridyltransferase (pyrophosphorylase) pathway for the
      catabolism of stachyose in the peduncles. The absence of the enzyme UDP-glucose
      hexose-1-phosphate uridyltransferase (EC 2.7.7.12) in this tissue rules out
      catabolism by the classical Leloir pathway. The incorporation of carbon from
      UDPglc into Glc-1-P as opposed to sucrose may be regulated by the activities of
      the uridyltransferases. Pyrophosphate, in the same concentration range, inhibits
      UDP-gal formation (Ki=0.58+/-0.10 mM) and stimulates Glc-1-P formation. The ratio
      of units of pyrophosphatase to units of Gal-1-P uridyltransferase was higher in
      peduncles from growing fruit than from unpollinated fruit. Modulation of carbon
      partitioning through a uridyltransferase pathway may be a factor controlling
      growth of the cucumber fruit. 

PMID- 24276943
TI  - Some relationships between the biochemistry of photosynthesis and the gas
      exchange of leaves.
AB  - A series of experiments is presented investigating short term and long term
      changes of the nature of the response of rate of CO2 assimilation to
      intercellular p(CO2). The relationships between CO2 assimilation rate and
      biochemical components of leaf photosynthesis, such as ribulose-bisphosphate
      (RuP2) carboxylase-oxygenase activity and electron transport capacity are
      examined and related to current theory of CO2 assimilation in leaves of C3
      species. It was found that the response of the rate of CO2 assimilation to
      irradiance, partial pressure of O2, p(O2), and temperature was different at low
      and high intercellular p(CO2), suggesting that CO2 assimilation rate is governed
      by different processes at low and high intercellular p(CO2). In longer term
      changes in CO2 assimilation rate, induced by different growth conditions, the
      initial slope of the response of CO2 assimilation rate to intercellular p(CO2)
      could be correlated to in vitro measurements of RuP2 carboxylase activity. Also,
      CO2 assimilation rate at high p(CO2) could be correlated to in vitro measurements
      of electron transport rate. These results are consistent with the hypothesis that
      CO2 assimilation rate is limited by the RuP2 saturated rate of the RuP2
      carboxylase-oxygenase at low intercellular p(CO2) and by the rate allowed by RuP2
      regeneration capacity at high intercellular p(CO2). 

PMID- 24276944
TI  - Some effects of enhanced UV-B irradiation on the growth and composition of
      plants.
AB  - Barley (Hordeum vulgare), corn (Zea mays), bean (Phaseolus vulgaris), and radish
      (Raphanus sativus) seedlings were continuously irradiated under a lighting device
      for 5-10 d at an increased ultraviolet (UV)-B fluence rate. In their growth
      parameters, composition, and leaf surface, these four species responded
      differently to the increased UV-B exposure. Bean seedlings suffered the most
      serious effects, radish and barley less, and corn was hardly influenced at all.
      In all plant species, the fresh weight, the leaf area, the amounts of
      chlorophylls, carotenoids and the galactolipids of the chloroplasts were reduced.
      The lipid content of the corn and bean seedlings also diminished. But all the
      irradiated plants showed a rise in their protein content compared to the control
      plants. The content of flavonoids increased in barley and radish seedlings by
      about 50%. The effects on growth parameters and composition were more extensive
      with increasing UV-B fluence rates, at least as shown in the case of barley
      seedlings. The fresh weights fell proportionally with the chlorophylls and
      carotenoids. In contrast, the flavonoid content of barley leaves rose parallel to
      the increasing UV-B fluence rates and reached 180% of the value in the control
      plants with the highest UV-B fluence rate. Scorching appeared regularly in the
      form of bronze leaf discoloration at the highest UV-B fluence rates. Scanning
      electron micrographs of the leaf surface of UV-B irradiated plants showed
      deformed epidermal structures. 

PMID- 24276945
TI  - Does magnetic resonance imaging predict future low back pain? A systematic
      review.
AB  - BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to
      identify pathology responsible for low back pain (LBP). However, the importance
      of findings on MRI remains controversial. We aimed to systematically review
      whether MRI findings of the lumbar spine predict future LBP in different samples
      with and without LBP. DATABASES AND DATA TREATMENT: MEDLINE, CINAHL and EMBASE
      databases were searched. Included were prospective cohort studies investigating
      the relationship between baseline MRI abnormalities of the lumbar spine and
      clinically important LBP outcome at follow-up. We excluded cohorts with specific
      diseases as the cause of their LBP. Associations between MRI findings and LBP
      pain outcomes were extracted from eligible studies. RESULTS: A total of 12
      studies met the inclusion criteria. Six studies presented data on participants
      with current LBP; one included a sample with no current LBP, three included a
      sample with no history of LBP and two included mixed samples. Due to small sample
      size, poor overall quality and the heterogeneity between studies in terms of
      participants, MRI findings and clinical outcomes investigated, it was not
      possible to pool findings. No consistent associations between MRI findings and
      outcomes were identified. Single studies reported significant associations for
      Modic changes type 1 with pain, disc degeneration with disability in samples with
      current LBP and disc herniation with pain in a mixed sample. CONCLUSIONS: The
      limited number, heterogeneity and overall quality of the studies do not permit
      definite conclusions on the association of MRI findings of the lumbar spine with
      future LBP (PROSPERO: CRD42012002342).

PMID- 24276946
TI  - CME instructions: gated SPECT in assessment of regional and global left
      ventricular function: an update.

PMID- 24276948
TI  - Automated screening for myelodysplastic syndromes through analysis of complete
      blood count and cell population data parameters.
AB  - The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index
      of suspicion to prompt bone marrow studies as well as subjective assessment of
      dysplastic morphology. We sought to determine if data collected by automated
      hematology analyzers during complete blood count (CBC) analysis might help to
      identify MDS in a routine clinical setting. We collected CBC parameters
      (including those for research use only and cell population data) and demographic
      information in a large (>5,000), unselected sequential cohort of outpatients. The
      cohort was divided into independent training and test groups to develop and
      validate a random forest classifier that identifies MDS. The classifier
      effectively identified MDS and had a receiver operating characteristic area under
      the curve (AUC) of 0.942. Platelet distribution width and the standard deviation
      of red blood cell distribution width were the most discriminating variables
      within the classifier. Additionally, a similar classifier was validated with an
      additional, independent set of >200 patients from a second institution with an
      AUC of 0.93. This retrospective study demonstrates the feasibility of identifying
      MDS in an unselected outpatient population using data routinely collected during
      CBC analysis with a classifier that has been validated using two independent data
      sets from different institutions.

PMID- 24276950
TI  - Systematic review and meta-analysis of percutaneous subclavian vein puncture
      versus surgical venous cutdown for the insertion of a totally implantable venous
      access device.
AB  - BACKGROUND: Totally implantable venous access devices (TIVADs) are commonly used
      in patients with cancer. Although several methods of implantation have been
      described, there is not enough evidence to support the use of a specific
      technique on a daily basis. The objective of this study was systematically to
      assess the literature comparing percutaneous subclavian vein puncture with
      surgical venous cutdown. METHODS: MEDLINE, Embase and the Cochrane Central
      Register of Controlled Trials were searched by two independent authors. No time
      limits were applied. A systematic review and meta-analysis was carried out
      according to the recommendations of the Cochrane Collaboration, including
      randomized clinical trials comparing primary percutaneous subclavian vein
      puncture with surgical venous cutdown. RESULTS: Six trials were included, with
      772 patients overall. The primary implantation failure rate was significantly
      lower for the percutaneous approach compared with surgical cutdown (odds ratio
      (OR) 0.26, 95 per cent confidence interval (c.i.) 0.07 to 0.94; P = 0.039). There
      was no evidence supporting a significant difference in terms of risk of
      pneumothorax, haematoma, venous thrombosis, infectious events or catheter
      migration. After taking between-study heterogeneity into account by using a
      random-effects model, procedure duration was not significantly longer for
      surgical cutdown: weighted mean difference +4 (95 per cent c.i. -12 to 20) min (P
      = 0.625). CONCLUSION: Percutaneous subclavian vein puncture is associated with a
      higher TIVAD implantation success rate and a procedure duration similar to that
      of surgical cutdown. Pneumothorax develops exclusively after percutaneous
      puncture and requires special attention from clinicians dealing with TIVAD
      insertion.

PMID- 24276951
TI  - The impact of the Iraq War on neonatal polio immunisation coverage: a quasi
      experimental study.
AB  - BACKGROUND: The public health consequences of the Iraq War (2003-2011) have
      remained difficult to quantify, mainly due to a scarcity of adequate data. This
      paper is the first to assess whether and to what extent the war affected neonatal
      polio immunisation coverage. METHOD: The study relies on retrospective neonatal
      polio vaccination histories from the 2000, 2006 and 2011 Iraq Multiple Indicator
      Cluster Surveys (N=64,141). Pooling these surveys makes it possible to
      reconstruct yearly trends in immunisation coverage from 1996 to 2010. The impact
      of the war is identified with a difference-in-difference approach contrasting
      immunisation trends in the autonomous Kurdish provinces, which remained
      relatively safe during the war, with trends in the central and southern
      provinces, where violence and disruption were pervasive. RESULTS: After
      controlling for individual and household characteristics, year of birth and
      province of residence, children exposed to the war were found to be 21.5
      percentage points (95% CI -0.341 to -0.089) less likely to have received neonatal
      polio immunisation compared with non-exposed children. CONCLUSIONS: The decline
      in neonatal polio immunisation coverage is part of a broader war-induced
      deterioration of routine maternal and newborn health services. Postwar strategies
      to promote institutional deliveries and ensure adequate vaccine availability in
      primary health facilities could increase dramatically the percentage of newborns
      immunised.

PMID- 24276949
TI  - The basic leucine zipper transcription factor ABSCISIC ACID RESPONSE ELEMENT
      BINDING FACTOR2 is an important transcriptional regulator of abscisic acid
      dependent grape berry ripening processes.
AB  - In grape (Vitis vinifera), abscisic acid (ABA) accumulates during fruit ripening
      and is thought to play a pivotal role in this process, but the molecular basis of
      this control is poorly understood. This work characterizes ABSCISIC ACID RESPONSE
      ELEMENT-BINDING FACTOR2 (VvABF2), a grape basic leucine zipper transcription
      factor belonging to a phylogenetic subgroup previously shown to be involved in
      ABA and abiotic stress signaling in other plant species. VvABF2 transcripts
      mainly accumulated in the berry, from the onset of ripening to the harvesting
      stage, and were up-regulated by ABA. Microarray analysis of transgenic grape
      cells overexpressing VvABF2 showed that this transcription factor up-regulates
      and/or modifies existing networks related to ABA responses. In addition, grape
      cells overexpressing VvABF2 exhibited enhanced responses to ABA treatment
      compared with control cells. Among the VvABF2-mediated responses highlighted in
      this study, the synthesis of phenolic compounds and cell wall softening were the
      most strongly affected. VvABF2 overexpression strongly increased the accumulation
      of stilbenes that play a role in plant defense and human health (resveratrol and
      piceid). In addition, the firmness of fruits from tomato (Solanum lycopersicum)
      plants overexpressing VvABF2 was strongly reduced. These data indicate that
      VvABF2 is an important transcriptional regulator of ABA-dependent grape berry
      ripening. 

PMID- 24276952
TI  - The Edmonton Symptom Assessment System (ESAS) as a screening tool for depression
      and anxiety in non-advanced patients with solid or haematological malignancies on
      cure or follow-up.
AB  - BACKGROUND: Symptoms' assessment should be considered a clinical practice routine
      in all cancer stages. The Edmonton Symptom Assessment System (ESAS) is a ten-item
      patient-rated symptom assessment developed and validated for population affected
      by cancer in different languages and cultures. The main objective of this study
      was to assess the performance of ESAS items on anxiety and depression when
      detecting Hospital Anxiety Depression Scale (HADS) 'cases'. METHODS: A cross
      sectional study was carried out on 194 non-advanced patients with solid (108) or
      hematologic malignancies on cure or follow up, Karnofsky Performance Status >=
      70, life expectancy > 6 months and no metastases. Patients were assessed by means
      of ESAS and by HADS. Receiving operator characteristic (ROC) analysis of ESAS
      anxiety and depression items versus cases of severe (cutoff 11) anxiety and
      depression according to HADS-specific subscales was performed. RESULTS:
      Depression and anxiety ESAS items correlated strongly (0.707, Spearman). Area
      under the curve ranged between 0.84 and 0.96 for the two ESAS items when
      detecting severe anxiety or depression HADS cases (cutoff = 11). ESAS anxiety or
      depression scores >3 detected quite well the severe depression HADS cases
      (Sensibility = 75-Specificity = 84, Sensibility = 87-Specificity = 90,
      respectively). CONCLUSIONS: Anxiety or depression ESAS items score >3 can be
      applied as a useful, easy and not time consuming screening tool for assessing
      anxiety and depression in non-advanced patients with solid or haematological
      malignancies.

PMID- 24276953
TI  - Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and
      vomiting following high-dose cisplatin in Chinese patients: a randomized, double
      blind, placebo-controlled phase III trial.
AB  - PURPOSE: Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated
      improved control of chemotherapy-induced nausea and vomiting (CINV) in previous
      studies. This is the first phase III study to evaluate the efficacy and
      tolerability of aprepitant in patients receiving highly emetogenic chemotherapy
      (HEC) in Asian countries. METHODS: This multicenter, double-blind, placebo
      controlled trial assessed the prevention of CINV during the acute phase (AP),
      delayed phase (DP), and overall phase (OP). Patients receiving HEC were
      randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2-3,
      aprepitant 80 mg) or a standard therapy group (days 1-3, placebo). Both groups
      received intravenous granisetron and oral dexamethasone. The primary end point
      was complete response (CR; no emesis and no use of rescue therapy) during the OP.
      RESULTS: Of the 421 randomized patients, 411 (98%) were assessable for efficacy;
      69.6% (142/204) and 57.0% (118/207) of patients reported CR during the OP in the
      aprepitant and standard therapy groups, respectively (P = 0.007). CR rates in the
      aprepitant group were higher during the DP (74.0% vs. 59.4%, P = 0.001) but were
      similar during the AP (79.4% vs. 79.3%, P = 0.942). Toxicity and adverse events
      were comparable in both groups. CONCLUSIONS: The addition of aprepitant to
      standard antiemetic treatment regimens for Chinese patients undergoing HEC
      provided superior CINV prevention and was well tolerated.

PMID- 24276954
TI  - Changes in compliance with Japanese antiemetic guideline for chemotherapy-induced
      nausea and vomiting: a nationwide survey using a distributed research network.
AB  - OBJECTIVE: Prophylaxis of chemotherapy (CT)-induced nausea and vomiting (CINV) is
      important for patient's quality of life and adherence to CT. Neurokinin receptor
      antagonist (NK1 antagonist) was marketed in Japan in December 2009 and the first
      guideline for antiemetics for CINV was released in May 2010 from Japan Society of
      Clinical Oncology (JSCO). We assessed changes in compliance with the JSCO
      guideline during the first 18 months from the launch of NK1 antagonist in Japan.
      METHODS: Patient-level data was extracted locally using a nationwide distributed
      research network consisting of 39 hospitals. Monthly compliance rates for acute
      (day of CT) and delayed (days 2-5) phases were summarized according to the emetic
      risks. RESULTS: In total, 81,739 CTs for 9,978 patients were analyzed.
      Prescription of oral NK1 antagonist was started in 31/39 hospitals during the
      study period. The compliance in acute phase for high emetic risk (HER) CTs
      gradually improved up to 39.3% whereas it reached only to 10-15% in delayed
      phase. The extra use of antiemetics decreased inversely to the increased
      compliance. Better compliance for HER CTs was associated with opioid use, younger
      age, second or later cycles, and CT regimens. Compliance in acute phase was
      better in inpatient whereas that in delayed phase was better in outpatients.
      CONCLUSIONS: A multi-hospital survey revealed that more than half of the HER CTs
      remained without accompanying the standard antiemetic therapies. Association with
      the compliance and CINV outcomes would be also interesting to explore.

PMID- 24276955
TI  - Patient and oncologist discussions about cancer care costs.
AB  - PURPOSE: Patient out-of-pocket costs are higher for cancer care than for any
      other health-care sector. Oncologist-patient discussions of costs are not well
      understood. We conducted an exploratory interview study to examine the frequency,
      patterns, attitudes, and preferences of both patients and providers on discussion
      of treatment costs. METHODS: We conducted semi-structured telephone interviews
      with oncology clinicians and people receiving chemotherapy at a large nonprofit
      health system. Multiple investigators conducted thematic analysis using modified
      content analysis, grounded theory, and interaction analysis methods. RESULTS:
      Patient themes included the relevance of cost to their experience, preference for
      the doctor to be the starting point of cost discussions, but relative infrequency
      of discussions with doctors or other care team member. Provider themes were an
      emphasis on clinical benefit above costs, conviction that cost-related decisions
      should rest with patients, and lack of access to treatment costs. Interest in
      discussing costs and barriers accessing cost information were common themes from
      both patients and providers. CONCLUSIONS: Doctors and patients want to discuss
      treatment costs but lack access to them. These data support growing evidence for
      a provider role in discussions of cost during cancer treatment planning.

PMID- 24276957
TI  - Utilizing bacterial flagellins against infectious diseases and cancers.
AB  - The flagellum is the organelle providing motility to bacterial cells and its
      activity is coupled to the cellular chemotaxis machinery. The flagellar filament
      is the largest portion of the flagellum, which consists of repeating subunits of
      the protein flagellin. Receptors of the innate immune system including Toll like
      receptor 5, ICE protease activating factor, and neuronal apoptosis inhibitory
      protein 5 signal in response to bacterial flagellins. In addition to inducing
      innate immune responses, bacterial flagellins mediate the development of adaptive
      immune responses to both flagellins and coadministered antigens. Therefore, these
      proteins have intensively been investigated for the vaccine development and the
      immunotherapy. This review describes the utilization of bacterial flagellins for
      the construction of vaccines against infectious diseases and cancer
      immunotherapy. Furthermore, the key factors affecting the performance of these
      systems are highlighted. 

PMID- 24276956
TI  - A systematic review and meta-analysis on the use of traditional Chinese medicine
      compound kushen injection for bone cancer pain.
AB  - PURPOSE: Bone cancer pain presents a clinical challenge with limitations of
      current treatments. Compound kushen injection (CKI) is a well-known traditional
      Chinese medicine (TCM) formulation in treatment of patients with bone cancer
      pain. The objective of this study is to assess the efficacy and safety of CKI for
      bone cancer pain. METHODS: A systematic literature search was conducted in nine
      databases until December 2012 to identify randomized controlled trials (RCTs) of
      CKI versus current western therapies for bone cancer pain. The primary outcome
      was total pain relief rate. The secondary outcomes were the quality of life and
      adverse events at the end of treatment course. The methodological quality of RCTs
      was assessed independently using six-item criteria according to the Cochrane
      Collaboration, and the level of evidence was assessed by the GRADE approach. All
      data were analyzed using Review Manager 5.1.0. RESULTS: Seven RCTs with 521
      patients from 2010 to 2012 were identified. Compared with radiotherapy or
      bisphosphonates, seven RCTs showed significant effects of CKI for improving pain
      relief in patients with bone cancer pain (n = 521, risk ratio (RR) = 1.25, 95 %
      CI (95 % confidence intervals (CI)), 1.13 to 1.38, p < 0.0001)), three RCTs for
      improving Karnofsky scoring (KPS) increase rate (n = 305, RR = 1.62, 95 % CI,
      1.32 to 1.99, p < 0.00001), 1 RCT for increasing KPS scores (n = 78, mean
      difference (MD) = 10.43, 95 % CI 4.76 to 16.10, p = 0.0003). 4 RCTs reported
      adverse effects in both the treatment and control groups. The patients treated
      with CKI achieved statistically significant reductions of incidences of
      leukopenia (n = 276, RR = 0.32, 95 % CI, 0.21 to 0.47, p < 0.00001) and nausea (n
      = 78, RR = 0.15, 95 % CI, 0.06 to 0.34, p < 0.00001). No severe adverse events
      were found and no treatment was stopped because of adverse events of CKI in the
      treatment groups. However, the studies were deemed to have a high risk of bias.
      CONCLUSION: This systematic review showed positive but weak evidence of CKI for
      bone cancer pain because of the poor methodological quality and the small
      quantity of the included trials. Future rigorously designed RCTs are required.

PMID- 24276958
TI  - SIGLEC-4 (MAG) Antagonists: From the Natural Carbohydrate Epitope to
      Glycomimetics.
AB  - Siglec-4, also known as myelin-associated glycoprotein (MAG), is a member of the
      siglec (sialic acid-binding immunoglobulin-like lectins) family. MAG binds with
      high preference to sialic acids alpha(2-3)-linked to D-galactose. Although the
      involvement and relevance of its sialic acid binding activity is still
      controversial, it could be demonstrated that interactions of MAG with sialylated
      gangliosides play an important role in axon stability and regeneration. In this
      article we describe in detail our current understanding of the biological role
      and the carbohydrate specificity of siglec-4. Furthermore, this review compiles
      the intensive research efforts leading from the identification of the minimal
      oligosaccharide binding epitope in gangliosides via micromolar oligosaccharide
      mimics to the development of small molecular weight and more drug-like sialic
      acid derivatives binding with low nanomolar affinities. Such compounds will be
      useful to elucidate MAG's biological functions, which are currently not fully
      understood. 

PMID- 24276959
TI  - Asymmetric hydroamination.
AB  - The direct addition of amine N-H bonds across an unsaturated carbon-carbon
      linkage gives fast and highly atom-economical access to amines. This review
      provides an overview of the most effective stereoselective methods using various
      catalyst systems based on alkali, alkaline earth, and transition metals, as well
      as enzymatic and organocatalytic approaches. Except for a few sporadic examples
      in the last century, this field has evolved primarily over the last decade.
      Catalyst systems have reached enantioselectivities exceeding 90% ee for many
      substrate classes, but significant challenges remain, in particular in the
      stereoselective intermolecular hydroamination of unactivated alkenes. 

PMID- 24276960
TI  - Time of our lives.

PMID- 24276961
TI  - Transference and the idea of God.
AB  - While many factors influence the course of therapy, based on empirical evidence a
      strong case can be made for the importance of religious beliefs influencing the
      process of transference. During a ten-year period of private psychiatric
      practice, the senior author saw 353 patients suffering from anxiety and neurotic
      depression. The form of treatment was individual, dynamic, psychoanalytically
      oriented psychotherapy with occasional use of psychotropic drugs. Forty percent
      of the patients who were seen were Catholic; forty percent were Protestant; and
      twenty percent were Jewish.Protestants, Catholics, and Jews bring differing
      conceptions of God to the transference phenomenon in individual psychotherapy.
      Basing findings on extensive clinical evidence, this study seeks to explain why
      this occurs, and the need for the psychotherapist to be aware of religious
      factors that influence the course of psychotherapy. 

PMID- 24276962
TI  - The impact of religion on men's blood pressure.
AB  - Most clinical studies examining the relation between religion and blood pressure
      status have focused on church attendance, finding lower pressures among frequent
      attenders. The present study examines the effect on blood pressure status of a
      religious meaning variable, importance of religion, both by itself and together
      with frequency of church attendance. The relation between blood pressure, self
      perceived importance of religion, and frequency of church attendance was examined
      among a rural sample of 407 white men free from hypertension or cardiovascular
      disease. The data confirmed an interaction between the effects of both religious
      variables on blood pressure status, with importance of religion having an even
      greater association with lower pressures than church attendance. Diastolic blood
      pressures of persons with high church attendance and high religious importance
      were significantly lower than those in the low attendance, low importance group.
      These differences persisted after adjusting the analyses for age, socioeconomic
      status, smoking, and weight-height ratio (Quetelet Index). The difference in mean
      diastolic pressures based on response to the religious importance variable alone
      was statistically and clinically significant, particularly among men aged 55 and
      over (6 mm) and among smokers (5 mm). These findings suggest that both religious
      attitudes and involvement may interact favorably in their effects on
      cardiovascular hemodynamics. 

PMID- 24276963
TI  - Religious celibacy from the celibate's point of view.
AB  - What do celibates consider the adaptive and maladaptive aspects of their celibate
      religious lifestyle? What role has celibacy played in understanding the
      differences between those who persevere and those who choose to resign from
      celibate religious life and/or ordained ministry? Using data from extensive
      interviews, this exploratory study begins to focus some of the perceived effects
      of celibacy upon personal development for both those who persevere in celibate
      religious life and those who resign. 

PMID- 24276964
TI  - Helping through touch: The embodiment of caring.
AB  - There is a power to touch, and a magic. Some call it mystery. The purpose of this
      paper is to reflect on the various meanings and uses of touch, particularly
      within the context of relationship and helping. There will be no attempt to
      formulate a protocol for touch or to lay claim to a definitive meaning for touch.
      Reflection about touch may instead clarify some of its meanings and dynamics
      while encouraging care providers to embrace the experience of helping-through
      touch. This paper supports a considered use of empathie touch because of its
      power and its ability to embody care. 

PMID- 24276965
TI  - Albert Schweitzer and international health.
AB  - Albert Schweitzer (1875-1965) was a medical missionary, theologian, philosopher,
      and musician and the only individual physician to receive the Nobel Peace Prize.
      His humanitar-ianism had a profound philosophical-religious basis, embodied in
      the concepts of "ethical mysticism" and "reverence for life." This paper outlines
      the relevance of Schweitzer's career to medical education and international
      health. The growing role of Western physicians in international health and in the
      prevention of nuclear war (and its medical consequences) is consistent with
      Schweitzer's active and universalist ethical principles aimed at the alleviation
      of the suffering shared by mankind. The example of Schweitzer and other
      individual physicians could be used to enhance participation of individual
      medical students and physicians in international health programs. 

PMID- 24276966
TI  - Care and the dynamics of social world.
AB  - The concept of "social world" is formulated for the purpose of deepening our
      understanding of the dynamics of inclusion, exclusion, and care in interpersonal
      interaction. "World" is defined as an "irreducible subject-object
      polarity.""Social world" is the "extremely fragile environment within which
      people meet," and is easily destroyed. With special attention to family and
      church life, the conditions for maintaining or losing this environment are
      examined. Three levels of social world are defined. On the highest level, mutual
      care, rather than shared opinion, is seen as the factor that facilitates the
      preservation of social world in the face of "world-threatening issues." 

PMID- 24276967
TI  - A block in the endocytosis of Rhizobium allows cellular differentiation in
      nodules but affects the expression of some peribacteroid membrane nodulins.
AB  - A transposon-induced mutant (T8-1) of Bradyrhizobium japonicum (61A76) was unable
      to develop into the nitrogen-fixing endosymbiotic form, the bacteroid. Comparison
      between this mutant and T5-95, an ineffective (non-nitrogen fixing, Fix(-))
      mutant, confirmed that the process of bacteroid development is a distinct phase
      of differentiation of the endosymbiont and is independent of nitrogen fixation
      activity. The T8-1 mutant was able to induce normal-size nodules which
      differentiated two plant cell types and contained numerous infection threads.
      However, the infected cells were devoid of bacteroids. Electron microscopy
      revealed that the ends of the infection threads were broken down in a normal
      manner once the thread had penetrated the cells, but the mutant was not
      internalized by endocytosis. The lack of peribacteroid membrane (PBM) in nodules
      induced by this mutant was correlated with a reduced level of expression of plant
      genes coding for PBM nodulins. These genes were expressed in the T5-95 mutant,
      showing that the low expression in T8-1 was not due to the lack of nitrogen
      fixation. One of the PBM nodulins, nodulin-26, was found at normal levels in the
      nodules which lack PBM, suggesting that there are at least two developmental
      stages in PBM biosynthesis. These data suggest that a coordination of plant and
      Rhizobium gene expression is required for the release and internalization of
      bacteria into the PBM compartments of infected cells of nodules. 

PMID- 24276968
TI  - Avocado cellulase: nucleotide sequence of a putative full-length cDNA clone and
      evidence for a small gene family.
AB  - A cDNA library was prepared from ripe avocado fruit (Persea americana Mill. cv.
      Hass) and screened for clones hybridizing to a 600 bp cDNA clone (pAV5) coding
      for avocado fruit cellulase. This screening led to the isolation of a clone
      (pAV363) containing a 2021 nucleotide transcribed sequence and an approximately
      150 nucleotide poly(A) tail. Hybridization of pAV363 to a northern blot shows
      that the length of the homologous message is approximately 2.2 kb. The nucleotide
      sequence of this putative full-length mRNA clone contains an open reading frame
      of 1482 nucleotides which codes for a polypeptide of 54.1 kD. The deduced amino
      acid composition compares favorably with the amino acid composition of native
      avocado cellulase determined by amino acid analysis. Southern blot analysis of
      Hind III and Eco RI endonuclease digested genomic DNA indicates a small family of
      cellulase genes. 

PMID- 24276969
TI  - Molecular characterization and genetic mapping of DNA sequences encoding the Type
      I chlorophyll a/b-binding polypeptide of photosystem I in Lycopersicon esculentum
      (tomato).
AB  - We report the isolation and characterization of a tomato nuclear gene encoding a
      chlorophyll a/b-binding (CAB) protein of photosystem I (PSI). The coding
      nucleotide sequence of the gene, designated Cab-6B, is different at eight
      positions from that of a previously isolated cDNA clone derived from the Cab-6A
      gene, but the two genes encode identical proteins. Sequence comparison with the
      cDNA clone revealed the presence of three short introns in Cab-6B. Genetic
      mapping experiments demonstrate that Cab-6A and Cab-6B are tightly linked and
      reside on chromosome 5, but the physical distance between the two genes is at
      least 7 kilobases. Cab-6A and Cab-6B have been designated Type I PSI CAB genes.
      They are the only two genes of this branch of the CAB gene family in the tomato
      genome, and they show substantial divergence to the genes encoding CAB
      polypeptides of photosystem II. The Type I PSI CAB genes, like the genes encoding
      PSII CAB proteins, are highly expressed in illuminated leaf tissue and to a
      lesser extent in other green organs. 

PMID- 24276970
TI  - Differential expression of oxygen-evolving polypeptide genes in maize leaf cell
      types.
AB  - Three polypeptides of 33 kD, 23 kD and 16 kD are released from maize photosystem
      II particles by alkaline Tris solution treatment and shown to cross-react with
      antisera to purified spinach oxygen-evolving (OE) polypeptides of 34 kD, 23 kD
      and 17 kD, respectively. They are not located exclusively in mesophyll cells but
      each is about 4 times more abundant in the thylakoid membranes of mesophyll than
      bundle sheath cells of etiolated, greening and green leaves. Three maize cDNA
      clones (OE33, OE23, OE16) have been identified by hybrid-selection, in vitro
      translation and immunoprecipitation with antisera against spinach OEs.
      Transcripts of all three genes are already detectable in both mesophyll and
      bundle sheath cells of etiolated leaves; however, they accumulate transiently and
      coordinately in mesophyll cells but remain at a constant low level in bundle
      sheath cells upon illumination of dark-grown maize seedlings. Moreover, the level
      of each protein increases in mesophyll cells following the accumulation of
      transcripts during greening and remains high in late greening and green leaves,
      despite the decline in each corresponding mRNA. The accumulation of all three OE
      proteins is also stimulated by light in bundle sheath cells without increases in
      their corresponding mRNAs. The preferential localization of these three proteins
      in mesophyll cells is due to both transcriptional and translational regulation. 

PMID- 24276971
TI  - Effect of abscisic and gibberellic acids on malate synthase transcripts in
      germinating castor bean seeds.
AB  - Several clones complementary to malate synthase mRNA have been identified in a
      complementary-DNA library to mRNA from castor bean endosperm. One of these clones
      has been used as a probe to measure levels of transcripts during seed germination
      and the effects of gibberellic acid and abscisic acid on these levels have been
      examined.Malate synthase transcripts increased during germination and GA3
      advanced their appearance in the endosperm. Exogenously applied ABA inhibited the
      accumulation of transcripts over a time course of germination but the addition of
      GA3 counteracted its inhibitory effects. The data confirmed previous reports
      which indicated that the action of both growth regulators was on transcript
      accumulation and that there is a coordinated induction of the enzymes involved in
      the lipid metabolism in oil seeds. 

PMID- 24276972
TI  - Localization, sequence and expression of the gene coding for tRNA(Pro) (UGG) in
      plant mitochondria.
AB  - The four Sal I fragments of wheat mitochondrial DNA containing the 18S and 5S
      ribosomal RNA genes were screened for the presence of tRNA genes. Upon
      sequencing, a tRNA(Pro) (UGG) gene was found in two of these four fragments. The
      localization of the corresponding gene on the maize mitochondrial genome was
      established. Transcriptional studies have shown that this gene is transcribed in
      wheat and maize mitochondria. The sequence of the corresponding tRNA(Pro) (UGG)
      of bean mitochondria was determined using in vitro post-labeling techniques. 

PMID- 24276973
TI  - Restriction site map of the Chlorella virus PBCV-1 genome.
AB  - The virus PBCV-1, which replicates in a Chlorella-like green alga, has a dsDNA
      genome. The DNA was mapped for BamHI, HindIII, and PstI restriction sites. The
      resulting map has a size of 333 kbp and is circular-indicating either covalently
      closed circular DNA or circularly permuted linear DNA. Several regions of
      repetitive DNA were also identified and located on the restriction map. 

PMID- 24276974
TI  - Light-stimulated accumulation of the peroxisomal enzymes hydroxypyruvate
      reductase and serine:glyoxylate aminotransferase and their translatable mRNAs in
      cotyledons of cucumber seedlings.
AB  - The development of peroxisomal enzymes in cotyledons of cucumber seedlings is
      strongly dependent on light. In light-grown seedlings, activities of two
      peroxisomal enzymes, hydroxypyruvate reductase (HPR) and serine: glyoxylate
      aminotransferase (SGAT), were barely detectable until three days postimbibition,
      after which time both activities increased rapidly and linearly for at least
      three days. In the dark, the activities of these enzymes increased slightly over
      the same time period, but only to about 5% to 10% of 7-day light-induced levels.
      When 51/2-day dark-grown seedlings were transferred into white light, activities
      of HPR and SGAT began to increase after approximately 8 h. HPR protein was shown
      by an immunoprecipitation assay to increase concurrently with enzymatic activity
      in both light- and dark-grown cotyledons. Immunoblotting results suggested that
      the amounts of SGAT-A and SGAT-B, the two subunits of SGAT, also developed along
      with SGAT activity. The relative levels of translatable mRNAs encoding HPR, SGAT
      A, and SGAT-B were also light-dependent, and increased with a developmental
      pattern similar to enzyme activity and protein levels in light- and dark-grown
      cotyledons. In 51/2-day dark-grown cotyledons that were transferred to the light,
      translatable mRNAs for SGAT-A and SGAT-B began to increase within 1 h of
      illumination and continued of increase rapidly and linearly for the next 24 h in
      the light to a new steady-state level that was 45 times that of dark controls.
      Translatable HPR mRNA exhibited a biphasic pattern of accumulation, with a three
      fold increase during the first 6 h of illumination, followed by an additional six
      fold increase between 8 and 24 h. The accumulation of translationally active mRNA
      for both enzymes preceded the accumulation of the corresponding protein and
      enzyme activity by about 8 h. Our data suggest that the rise in enzyme activity
      depends on an increase in translatable mRNA for these enzymes and is regulated at
      a pretranslational level, most likely involving transcription of new mRNA. 

PMID- 24276975
TI  - Mitochondrial DNA rearrangements in Pennisetum associated with reversion from
      cytoplasmic male sterility to fertility.
AB  - Endonuclease restriction fragment patterns of Pennisetum americanum L.
      mitochondrial DNAs (mtDNAs) from a cytoplasmic male-sterile (CMS-A1), fertile
      revertants and a normal fertile cytoplasm were variable, while chloroplast DNA
      from those lines lacked variation. Comparisons between mtDNAs of CMS-A1
      (parental) and fertile revertant lines revealed the presence of a unique 4.7 kbp
      PstI fragment in the sterile line that was not detected in any of the revertant
      lines. A 9.7 kbp PstI fragment was found in all of the revertants, but not in the
      CMS-A1. Neither of those fragments was found in the normal cytoplasm mtDNA.
      Hybridization studies revealed two sets of multiple homologies: 1) the 4.7 kbp
      fragment had homology with a 10.9 kbp and a 13.6 kbp fragment; and 2) the 9.7 kbp
      fragment was homologous with the 13.6 kbp fragment. The presence of those two
      repeated mitochondrial sequences on the altered fragments suggests that they may
      be involved in the recombinational associated events with reversion from CMS to
      fertility in P. americanum. 

PMID- 24276976
TI  - Characterization of a cDNA encoding ricin E, a hybrid ricin-Ricinus communis
      agglutinin gene from the castor plant Ricinus communis.
AB  - Two classes of ricin cDNA clones have been identified and sequenced. The cDNA
      clone pBL-1 closely matches in nucleotide sequence the ricin genomic clone pAKG
      previously described by Halling et al., 1985 (Nucl. Acids Res. 13:8019). A second
      group of cDNA clones, represented by pBL-3, encode a hybrid protein (ricin E),
      having a ricin-like A chain and N-terminal half of the B chain and an RCA
      (Ricinus communis agglutinin)-like C-terminal half of the B chain. 

PMID- 24276977
TI  - Effects of selenium on chemical carcinogenesis : Comparative effects of
      antioxidants.
AB  - Chemical carcinogenesis can be characterized by a sequence of events leading to
      the development of tumors. Selenium (Se) inhibition of colon, liver, and lung
      carcinogens is demonstrated. Using the male Sprague Dawley rat model Se inhibited
      the colon tumor incidence in 1,2-dimethylhydrazine (DMH) treated rats and reduced
      the total number of colon tumors in methylazoxymethanol (MAM) treated rats.
      Selenium inhibited 2-acetylaminofluorene (AAF) and 3'-methyl-4
      dimethylaminoazobenzene (3'-MeDAB) hepatocarcinogenesis. The hepatic tumor
      incidence induced by 3'-MeDAB was reduced by both inorganic Se (Na2SeO3) and by
      organic Se (Se-yeast) supplements.In vitro systems have been studied in an effort
      to decipher the inhibitory properties of Se on the multistage origin of tumors
      induced by chemical carcinogens. Current studies suggest that the protective
      effect of Se against AAF hepatocarcinogenesis may be correlated with a change in
      AAF metabolism. The mutagenicity of AAF and AAF metabolites inSalmonella
      typhimurium TA1538 is decreased by Se. Additionally, Se reduced N-t-OH-AAF
      induction of sister chromatid exchange (SCE) frequencies in whole blood cultures,
      and also reduced aryl hydrocarbon hydroxylase activity using benzo(a) pyrene as
      substrate.The comparative effects of antioxidants on DMH induction of colon
      tumors are presented in detail. Supplements of 4 ppm Se to the drinking water,
      1.2% ascorbic acid (V c ) to the diet or 0.5% butylated hydroxytoluene (BHT) to
      the diet of DMH-treated rats reduced the colon tumor incidence of DMH controls
      from 64 to 31% (Se), 38% (V c ), and 43% (BHT). The colon tumor incidence in DMH
      treated rats receiving a combination of Se+V c increased to 83%, while the
      combination of Se+BHT decreased the colon tumor incidence to 55%. The growth and
      survival of rats provided long-term supplements of 4 ppm Se in the drinking water
      are compared with untreated controls. 

PMID- 24276978
TI  - Metal binding drugs induce synthesis of four proteins in normal cells.
AB  - The synthesis of four proteins in chick embryo cells in culture is induced by
      exposure to several metal binding drugs and several cations. We reported
      previously that two chelating agents, kethoxal bis(thiosemicarbazone) and
      disulfiram induce these proteins. We now extend these findings to include 8
      hydroxyquinoline, ortho-phenanthroline, and thiosemicarbazide. The non-chelating
      analogues of these latter three compounds; 4-hydroxyquinoline,
      metaphenanthroline, and semicarbazide, do not induce. Other chelating agents,
      such as thenoyl trifluoroacetone, mercaptopyridine N-oxide,
      mercaptobenzothiazole, and methimazole induce. However, not all chelators induce
      since EDTA, penicillamine, alpha,alpha-dipyridyl, and several others are
      ineffective.Several cations, such as copper, zinc, cadmium, and mercuric ions
      induce, but cobalt, nickel, manganese, iron, lead, and platinum do not. The
      anions arsenite and arsenate induce, but bromide, dichromate, fluoride,
      metabisulfite, molybdate, nitrite, permanganate, phosphate, sulfite, and sulfate
      ions do not.The chelating agents that induce the proteins are ionophores
      for(64)Cu. The chelating agents that do not induce, such as EDTA, penicillamine,
      and the nonchelating analogs of the inducers, are not ionophores for copper.Since
      arsenite induces but is not a copper ionophore, we hypothesize that the common
      mechanism for both these compounds and the inducing cations is an interaction
      with a sulfhydryl group site. 

PMID- 24276979
TI  - The effect of various seleno-compounds on ehrlich ascites tumor cells.
AB  - The effect of various concentrations and forms of selenium on in vitro viability
      of Ehrlich Ascites Tumor Cells (EATC) was investigated. Sodium selenite, selenium
      dioxide, seleno-DL-cystine, and seleno-DL-methionine, dramatically decreased EATC
      viability as measured by dye exclusion. Sodium selenate only marginally decreased
      EATC viability. Cell viabilities decreased with increasing selenium in the
      incubation media and as a function of time. Viabilities determined by dye
      exclusion did not correlate with the inhibition of tumor growth observed after
      treatment with selenium. Intraperitoneal injections of selenite in mice
      previously inoculated with EATC significantly inhibited tumor development.
      Delaying intraperitoneal injections of selenite to 5 and 7 days after inoculation
      of mice with EATC reduced the effectiveness of this nutrient on the inhibition of
      EATC growth. Incubation of EATC in vitro with supplemental selenium prior to
      injection of mice completely inhibited EATC development in vivo before any
      appreciable alteration in cell viability was observed. 

PMID- 24276980
TI  - Epidemiological study of chromium platers in Japan.
AB  - A cohort study on platers in Tokyo was carried out using the records of the Tokyo
      Health Insurance Society of Plating Industry. The type of work and chromium
      exposure history of each member of this society was investigated by a
      questionnaire sent to the manager of each factory. The recovery rate of the
      questionnaire was 70.5%. Survival information on retired subjects was obtained
      from the offices of Japanese family registration system ("koseki").As the result,
      among 889 male chromium platers who were followed up from April 1, 1970 to
      September 30, 1976, 19 deaths were observed, but there were no cases of lung
      cancer. The observed number of deaths was only 50% of the expected number, which
      had been calculated using the annual male mortality by age of Tokyo. In contrast,
      a slightly higher number of deaths than expected (107%) was observed in the
      control group consisting of workers selected from the same factories as the
      chromium platers. Two types of possible error were considered in this study: the
      first is that deaths from the chromium-exposed group had been incorrectly
      assigned to the control group, and the second is that the 30% of nonresponders
      included a significant number of factories where chromium-related deaths had
      occurred.However, the response for surviving cases on the history of chromium
      handling is considered to be reliable. Thus it was decided to conduct a further
      study focusing on those workers alive on October 1, 1976. 

PMID- 24276981
TI  - The time-related subcellular distribution of chromium in the rat liver cell after
      intravenous administration of Na2 (51)CrO 4.
AB  - After intravenous administration of Na2 (51)CrO4 to rats the subcellular
      distribution of(51)Cr was determined at different time intervals after dosage. A
      time-related compartment shift from the cytosol into the mitochondrial and
      nuclear fractions was demonstrated. Dialysis studies indicated a firmer binding
      of(51)Cr to the mitochondrial and nuclear fractions than to the cytosol. Indirect
      evidence is presented that reduction from CrVI to CrIII takes place primarily
      inside the mitochondria. The hypothesis is put forward that reduction from Cr(VI)
      to Cr(III) may take place at any intracellular site where electron donors are
      available. Electron donors in the different intracellular organelles are
      discussed. 

PMID- 24276982
TI  - Chromate metabolism in liver microsomes.
AB  - The carcinogenicity and mutagenicity of various chromium compounds have been
      found to be markedly dependent on the oxidation state of the metal. The
      carcinogen chromate was reduced to chromium(III) by rat liver microsomes in
      vitro. Metabolism of chromate by microsomal enzymes occurred only in the presence
      of either NADPH or NADH as cofactor. The chromium(III) generated upon metabolism
      formed a complex with the NADP(+) cofactor. Significant binding of chromium to
      DNA occurred only when chromate was incubated in the presence of microsomes and
      NADPH. Specific inhibitors of the mixed function oxidase enzymes, 2'-AMP,
      metyrapone, and carbon monoxide, inhibited the rate of reduction of chromate by
      microsomes and NADPH. The possible relationship of metabolism of chromate and its
      interaction with nucleic acids to its carcinogenicity and mutagenicity is
      discussed. 

PMID- 24276984
TI  - Introduction of a new policy of no nighttime appendectomies: impact on
      appendiceal perforation rates and postoperative morbidity.
AB  - BACKGROUND: Working hour limitations and tight health care budgets have posed
      significant challenges to emergency surgical services. Since 1 January 2010,
      surgical interventions at Berne University Hospital between 23:00 and 08:00 h
      have been restricted to patients with an expected serious adverse outcome if not
      operated on within 6 h. This study was designed to assess the safety of this new
      policy that restricts nighttime appendectomies (AEs). METHODS: The patients that
      underwent AE from 1 January 2010 to 31 December 2011 ("2010-2011 group") were
      compared retrospectively with patients that underwent AE before introduction of
      the new policy (1 January 2006-31 December 2009; "2006-2009 group"). RESULTS:
      Overall, 390 patients were analyzed. There were 255 patients in the 2006-2009
      group and 135 patients in the 2010-2011 group. Patients' demographics did not
      differ statistically between the two study groups; however, 45.9 % of the 2006
      2009 group and 18.5 % of the 2010-2011 group were operated between 23:00 and
      08:00 h (p < 0.001). The rates of appendiceal perforations and surgical site
      infections did not differ statistically between the 2006-2009 group and the 2010
      2011 group (20 vs. 18.5 %, p = 0.725 and 2 vs. 0 %, p = 0.102). Additionally, no
      difference was found for the hospital length of stay (3.9 +/- 7.4 vs. 3.4 +/- 6.0
      days, p = 0.586). However, the proportion of patients with an in-hospital delay
      of >12 h was significantly greater in the 2010-2011 group than in the 2006-2009
      group [55.6 vs. 43.5 %, p = 0.024, odds ratio (95 % confidence interval 1.62 (1.1
      2.47)]. CONCLUSIONS: Restricting AEs from 23:00 to 08:00 h does not increase the
      perforation rates and occurrence of clinical outcomes. Therefore, these results
      suggest that appendicitis may be managed safely in a semielective manner.

PMID- 24276983
TI  - Mechanisms of metal carcinogenesis.
AB  - Experimental observations that pertain to mechanisms of metal carcinogenesis are
      summarized, with emphasis upon (a) interactions of metals with nucleic acids in
      vitro; (b) impairment by metals of the fidelity of DNA replication by DNA
      polymerase in vitro; (c) mutagenicity of metals in microorganisms; (d)
      cytogenetic aberrations induced by metals in tissue culture cells; (e) induction
      by metals of neoplastic transformation of tissue culture cells; and (f) nuclear
      uptake of metals in vivo and concomitant inhibitory effects of metals on
      synthesis of nucleic acids. Considered in toto, the experimental data support the
      somatic mutation hypothesis of chemical carcinogenesis. Sufficient experimental
      evidence is available regarding four carcinogenic metals (As, Be, Cr, and Ni) to
      permit speculations about the molecular reactions whereby these metals may induce
      somatic mutations. 

PMID- 24276985
TI  - Using protamine can significantly reduce the incidence of bleeding complications
      after carotid endarterectomy without increasing the risk of ischemic cerebral
      events.
AB  - BACKGROUND: Controversy persists regarding the use of protamine sulfate (PS)
      during carotid endarterectomy (CEA), chiefly because of conflicting experiences
      reporting both less bleeding and a higher stroke risk. The goal of the present
      study was to test the hypothesis that reversing heparin with PS after CEA
      significantly reduces the incidence of bleeding complications without increasing
      the risk of postoperative stroke. METHODS: From January 2010 to December 2012 all
      consecutive patients undergoing CEA under general anesthesia at our institution
      received 5,000 U of heparin prior to carotid clamping, which was partially (half
      dose) reversed with PS 25 mg immediately after declamping (group I).
      Heparinization had never been reversed with PS in earlier CEAs performed from
      1998 to 2009 at the same institution (group II). All patients were assessed
      preoperatively and postoperatively by a neurologist, and cerebral magnetic
      resonance imaging was performed in all group I patients to exclude any silent
      cerebral infarction. End points of the study were bleeding complications,
      perioperative (30-day) stroke, and death. RESULTS: Overall, 219 CEAs (201
      patients) were performed in group I, and 1,458 CEAs (1,294 patients) in group II.
      Demographics, risk factors, and preoperative antiplatelet medication were
      comparable in the two groups. The incidence of adverse events (group I vs group
      II) was as follows: stroke (0 vs 0.5 % [8/1,458], p = 0.27); death (0 vs 0 %);
      neck bleeding (0 vs 8.2 % [120/1,458], p < 0.001). CONCLUSIONS: The results of
      the present study demonstrate that (1) partially neutralizing heparin with PS
      after CEA can significantly reduce the risk of bleeding complications, and (2)
      there is no association between the administration of PS and the incidence of
      postoperative stroke.

PMID- 24276986
TI  - Surgery indeed has an important role in long-term outcome in patients with
      pancreatic head cancer.

PMID- 24276987
TI  - Recurrent laryngeal nerve monitoring during thoracoscopic esophagectomy.
AB  - INTRODUCTION: There have been several reports on the feasibility and curability
      of thoracoscopic esophagectomy, which may reduce injury to the thoracic cage and
      decrease the invasiveness of surgery. Although the recurrent laryngeal nerve
      (RLN) is identified and kept intact during operations, RLN palsy sometimes
      occurs. Currently, surgical aides, including intraoperative neurological
      monitoring, are being utilized to avoid RLN injury during thyroid surgery. This
      system is utilized during thoracoscopic esophagectomy in the prone position.
      PATIENTS AND METHODS: Seven consecutive patients (six men, one woman; age range
      62-74 years; mean 68 years) were included. Patients underwent general anesthesia
      and were intubated using the NIM TriVantageTM electromyography (EMG) tube. One
      lung ventilation was performed with an endobronchial blocker. Thoracoscopic
      esophagectomy was performed in the prone position. The nerve stimulator was
      calibrated to 0.5 mA, and after the RLN was visually identified it was
      subsequently stimulated, which also confirmed normal machine functioning. In some
      situations, in the absence of a response, stimuli were increased to 1.0 mA and
      then 2.0 mA. RESULTS: Intraoperatively, all seven patients had their nerve
      signals monitored. In one case, a nerve signal disappeared after complete lymph
      node dissection along the left RLN. This system could identify the site of
      injury, and the thoracoscopic magnified view allowed the disrupted point to be
      located precisely. When we checked VTR after surgery, the source of injury was
      one point tension of the nerve pulled by fiber during lymph node dissection.
      CONCLUSIONS: Intraoperative RLN monitoring during thoracoscopic esophagectomy in
      the prone position, with one-lung ventilation performed using the TriVantageTM
      EMG tube and a bronchial blocker, is technically feasible, easy, and reliable.

PMID- 24276988
TI  - Tissue expander-assisted ventral hernia repair for the skin-grafted damage
      control abdomen.
AB  - PURPOSE: To describe a novel technique using tissue expanders that allows skin
      coverage over large ventral hernia repairs after damage control laparotomy,
      including patients with stomas. METHODS: A retrospective study of a single
      author's experience with the technique. RESULTS: Tissue expanders were placed in
      the lateral abdominal wall skin adjacent to stomas and expanded over a short 6
      week course. The expanders successfully stretched the skin to provide coverage
      over the large ventral hernia mesh repairs without infectious complications.
      CONCLUSIONS: The described technique is well tolerated by patients and very
      useful to provide skin coverage over large ventral hernia defects without
      infectious complications.

PMID- 24276990
TI  - Light-induced variation in phenolic levels in foliage of rain-forest plants : I.
      Chemical changes.
AB  - Levels of phenolic secondary metabolites in the leaves of four west African rain
      forest plants,Acacia pennata, Cynometra leonensis, Diopyros thomasii, andTrema
      guineensis, were correlated with incident light intensity at both the inter- and
      intraindividual level. Enhanced phenolic levels under high light intensity
      appeared to be due to production of both polyphenolics (condensed and
      hydrolyzable tannins) and simple phenolics. InTrema guineensis, where it is
      possible to separate leaves in terms of both their age and the light incident
      upon them, condensed tannin production progressed differently during the
      development of "sun" and "shade" leaves, suggesting continuing production of new
      oligomers in the former but not in the latter. The results of this study suggest
      that the production of phenolics in relation to variation in incident light is a
      finely tuned process, which must be explained in terms of plant physiology and
      intermediate metabolism rather than in terms of resource allocation or a direct
      response to herbivory. 

PMID- 24276991
TI  - Light-induced variation in phenolic levels in foliage of rain-forest plants : II.
      Potential significance to herbivores.
AB  - The allelochemic activity of the polyphenolics isolated from the leaves of four
      west African rain-forest plants,Acacia pennata, Cynometra leonensis, Diospyros
      thomasii, andTrema guineensis, was examined by means of protein precipitation
      experiments to estimate their specific activity as precipitants. Results
      indicated that light-induced phenol synthesis in the more heavily insolated
      foliage of a species led to greater protein-precipitating capacity in these
      leaves. It is considered doubtful that this produced a quantitative difference in
      protein availability to an herbivore as, on average, even in the most shaded
      leaves there was sufficient tannin present to precipitate all the foliar protein.
      However, taking into account the considerable variability inherent in the results
      obtained and the adaptations herbivores possess to circumvent the antinutritional
      properties of tannins, it was concluded that shaded foliage was generally likely
      to present a nutritionally more acceptable food package on a statistical basis
      but that acceptable leaves could be found from throughout the light continuum
      encountered in any of the species studied. 

PMID- 24276989
TI  - The prognostic value of Foxp3+ tumor-infiltrating lymphocytes in patients with
      glioblastoma.
AB  - Forkhead box protein 3 (Foxp3) is known as a specific marker for regulatory T
      cells which contribute to immunosuppression in tumor microenvironment. However,
      existing studies regarding clinical significance of Foxp3+ tumor-infiltrating
      lymphocytes (TILs) in glioblastoma (GBM) remained discrepant. In this study, we
      aimed to explore whether this subtype of TILs correlated with prognosis in
      patients with GBM. Foxp3+ TILs as well as CD8+ ones were detected by
      immunohistochemistry on paraffin-embedded tumor samples from 62 patients.
      Staining for p53, MGMT and Ki-67 were also performed. The correlation of TIL
      subtypes with clinicopathologic features were analyzed. Progression-free survival
      (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and
      compared using log-rank test. Independent prognostic factors for PFS and OS were
      determined through univariate and multivariate analysis. Significant correlation
      was found between Foxp3 and CD8 expression (P = 0.003), but not between TIL
      subtypes and clinicopathologic characteristics. Patients with higher density of
      Foxp3+ TILs showed relatively shorter PFS (P < 0.001) and OS (P = 0.003) whereas
      patients with higher density of CD8+ TILs obtained no significant differences in
      survival. Survival analysis based on molecular classifications further clarified
      these predictive values. Univariate and multivariate analysis revealed that
      frequency of Foxp3+ TILs was probably associated with both PFS (P = 0.002) and OS
      (P = 0.003). In conclusion, the results suggest that Foxp3 positive infiltrates
      could provide an independent predictive factor in GBM.

PMID- 24276992
TI  - Novel 2-ethyl-5-alkylpyrrolidines in the venom of an australian ant of the
      genusMonomorium.
AB  - Novel 2-ethyl-5-alkylpyrrolidines and their corresponding 1-pyrrolines have been
      identified as poison gland products from an unidentified Australian species
      ofMonomorium. The major alkaloids present in the venom of this ant aretrans-2
      ethyl-5-undecylpyrrolidine andtrans-2-ethyl-5-(12-tridecen-1-yl)pyrrolidine. The
      position of the double bond in the latter was established from its dimethyl
      disulfide adduct after the amine function had been protected, and the
      stereochemistry of the alkyl groups was determined by direct comparison with
      synthetic compounds. The corresponding 1-pyrrolines were also detected in varying
      amounts in this venom. The pyrrolidines and 1-pyrrolines possess considerable
      insecticidal activity when evaluated against termite workers. The alkaloidal
      venoms ofMonomorium appear to be an important factor contributing to the success
      of these small ants both as competitors and as predators. 

PMID- 24276993
TI  - Specificity of male response to multicomponent pheromones in noctuid
      mothsTrichoplusia ni andPseudoplusia includens.
AB  - The response of male cabbage looper (CL) and soybean iooper (SBL) moths was
      observed in the flight tunnel and measured in field tests to the six-component CL
      pheromone, the five-component SBL pheromone, and toZ7-12: OAc, the major
      component common to each pheromone. In both the flight tunnel and the field, male
      CL exhibited significantly greater levels of response to their six-component
      blend than toZ7-12: OAc alone. A low level of cross-attraction of male CL to the
      SBL pheromone was observed in both the flight tunnel and the field, but it was
      quantitatively and qualitatively similar to their response toZ7-12: OAc alone.
      Thus the minor components of the SBL blend did not appear to disrupt the flight
      behavior of male CL. With respect to SBL, in the flight tunnel males also
      exhibited a greater level of response to the five-component blend compared toZ7
      12: OAc, but in the field their response was not significantly different to
      either treatment. There was also a low level of cross-attraction of male SBL to
      the CL blend, but this appeared to involve a significant arrestment effect on the
      upwind flight of males, as well as a difference in male sensitivity to the blend
      of components compared withZ7-12: OAc alone. The observed arrestment effect may
      have been due to male perception of one or more minor components of the CL
      pheromone. The results show that the multicomponent pheromones of these species
      function effectively as specific mating signals and that discrimination of odor
      quality by male moths can occur as the result of minor components affecting male
      sensitivity or their upwind flight response to the pheromone. 

PMID- 24276994
TI  - Toxicity of terpenoid deterrents to the leafcutting antAtta cephalotes and its
      mutualistic fungus.
AB  - Four natural products, of varying activity as deterrents of leafcutter attack,
      were tested for their effects on ant survival and on the growth of the
      mutualistic attine fungus. The substances were incorporated into an artificial
      liquid diet for bioassays on the ants or included in an agar culture medium for
      fungus growth-inhibition studies. Three of the four compounds exhibited
      deleterious effects on either adult leafcutting ants or their mutualistic fungus,
      and there appeared to be some correlation between deterrency and activity in
      these toxicity assays. The implications of these findings for leafcutting ant
      foraging patterns are discussed. 

PMID- 24276995
TI  - Effects of allelopathic compounds of corn pollen on respiration and cell division
      of watermelon.
AB  - The effects of the allelopathic compounds of an "'ethanolic extract" of corn
      pollen on growth, respiration, and cellular division of watermelon (Citrullus
      lanatus, var. peacock improved) were studied. Bioassays with the ethanolic
      extract showed an inhibition of radicle and hypocotyl growth. The effects on
      respiration were observed in isolated watermelon hypocotyl mitochondria. The
      ethanolic extract acts as an inhibitor of the electron pathway, decreasing oxygen
      consumption in state 3, with malate and succinate substrates. The specific
      inhibition site probably is located before the cytochromec. Ascorbate-TMPD as
      substrate reversed the inhibitory effect of the ethanolic extract. An evaluation
      of the mitotic index was made in slide preparations of previously treated
      meristematic cells. A decrease in mitotic activity of more than 50% was found, as
      well as irregular and pycnotic nuclei. The data obtained from this study reflect
      an important mechanism of action of the allelopathic compounds of corn pollen. 

PMID- 24276996
TI  - Pheromonal covariation and kinship in social beeLasioglossum zephyrum
      (Hymenoptera: Halictidae).
AB  - Both males and females of the primitively eusocial beeLasioglossum zephyrum can
      distinguish among female conspecifics with regard to genealogical relationship.
      Closely related females covary with respect to Dufour's gland pheromone products
      which are believed to function in individual or kin recognition. This is the
      first report of a population-wide parallel between similarity of communicative
      glandular product and genetic similarity. 

PMID- 24276997
TI  - Factors influencing release of hostmarking pheromone byRhagoletis pomonella
      flies.
AB  - The effect of fly or fruit treatments on quality and/or quantity of host-marking
      pheromone (HMP) trail substance released by apple maggot flies (Rhagoletis
      pomonella) following oviposition was evaluated. Among flies, considerable
      variation existed in the amount of HMP substance deposited, but overall, the
      amount of substance released on successively offered fruit (over a day or a week)
      did not change appreciably. Fly diet did not influence pheromone activity. Older
      flies (28 days) or smaller flies released less or less active HMP trail substance
      than younger flies (14 days) or larger flies. Females deposited a similar amount
      of trail substance on large (18-19 mm diam.) or HMP-marked fruit as on small (12
      13 mm) or unmarked fruit. Starvation reduced the amount of measurable trail
      substance deposited but resulted in a more active HMP deposition. Discrepancy
      between trail measurement and behavioral bioassay results for the starvation
      treatment indicated that trail measurement results may be misleading under
      conditions that reduce gut contents of the fly. 

PMID- 24276998
TI  - Effect of verbenone on response ofDendroctonus brevicomis toexo-Brevicomin,
      frontalin, and myrcene.
AB  - exo-Brevicomin (E), frontalin (F), and myrcene (M) were released at two rates 10
      fold apart with verbenone at four rates 10-fold apart, and without verbenone in
      plots with one trap on a vertical cylinder at the pheromone source and one trap
      on each of four cylinders 5 m away. Catch of the western pine beetleDendroctonus
      brevicomis decreased with increasing levels of verbenone at both release rates of
      EFM, but not all differences in catch were statistically significant.
      Significantly more beetles were caught at the high rate of EFM than at the low
      rate, combining all rates of verbenone. The percent of total beetles caught at
      the center trap tended to decrease with increasing rates of verbenone, but the
      only statistically significant differences were at the low rate of EFM. 

PMID- 24276999
TI  - Behavioral responses of crayfish (Orconectes virilis andOrconectes rusticus) to
      chemical feeding stimulants.
AB  - We conducted two experiments to assess how chemical stimuli affect feeding
      behavior, grooming, and walking in the crayfishesOrconectes virilis andOrconectes
      rusticus. In the first experiment,O. virilis was tested with 29 amino acids; in
      the second experiment,0. rusticus was tested with 12 amino acids, 13 additional
      single compounds, and two six-compound mixtures. InO. virilis, the following
      amino acids, in order of potency, elicited feeding movements:L-isoleucine,
      glycine, hydroxy-L-proline,L-glutamate,L-valine, and B-alanine. Grooming
      increased in response toL-phenylalanine,L-tryptophan,L-tyrosine,L-leucine,L
      methionine, and D-aspartate. InO. rusticus, both mixtures and the following
      single compounds, in order of potency, elicited feeding movements: cellobiose,
      sucrose, glycine, maltose, glycogen, nicotinic acid methyl ester, putrescine,
      andL-glutamate. Grooming increased in response to putrescine only, and walking
      increased in response to glycogen only. The responsiveness of these crayfishes to
      a wide variety of chemicals may reflect the omnivorous foraging habits of these
      crustaceans. 

PMID- 24277000
TI  - Amino acid chemoreception: Effects of ph on receptors and stimuli.
AB  - A current model of amino acid chemoreception has generated the idea that pH
      affects the efficiency of stimulus-receptor binding by altering the charge
      distribution on stimulus molecules. The model suggests that amino acids are
      maximally stimulatory near their isoelectric points. We point out that, within a
      broad range of pH values, changes in stimulant amino acids cannot account for
      altered chemoresponsiveness. We suggest instead that pH-induced changes in
      chemoreception are a result of changes in charge distribution on the protein
      receptor. 

PMID- 24277001
TI  - Novel, species-typical esters from preputial glands of sympatric voles,Microtus
      montanus andM. pennsylvanicus.
AB  - Olfactory signals may facilitate species recognition between the sympatric
      voles,Microtus montanus andM. pennsylvanicus. In an effort to isolate and
      identify compounds that might contribute to such a chemical communication system,
      the preputial glands of those voles have been examined. Morphological
      examinations show both vole species possess preputial glands; however, the glands
      ofM. montanus are much larger than those ofM. pennsylvanicus. Gas Chromatographie
      analysis revealed that the preputial glands ofM. montanus contain a series of
      species-typical lipids that are not found inM. pennsylvanicus. Using gas
      chromatography-mass spectrometry and nuclear magnetic resonance spectrometry, the
      species-typical lipids were identified as esters of branched, saturated, and
      unsaturated C5 and C4 alcohols and straight-chain C16, and "iso" branched C17
      fatty acids. This is the first description of such esters from mammalian tissues.
      The results are discussed relative to the possibility that the species-typical
      esters act as species recognition cues for the sympatric voles. 

PMID- 24277002
TI  - Electroantennogram responses of the mediterranean fruit fly,Ceratitis capitata,
      to a spectrum of plant volatiles.
AB  - Electroantennograms (EAGs) were recorded from unmated, laboratory-reared, male
      and femaleCeratitis capitata (medfly) in response to a range of C1 and C2 to C12
      carbon chain-length aliphatic alcohols, aldehydes, acetates, and acids, and
      lactones, some of which are known volatiles from leaves and fruits. A large
      degree of EAG response uniformity between the sexes was observed, with only eight
      of the 70 compounds tested eliciting significantly larger amplitude EAG responses
      from female than male antennae. In general, for the five functional-group series
      tested, aldehydes and alcohols elicited greater responses than acetates,
      lactones, and acids. The unsaturated alcohols, aldehydes, acetates, and acids
      elicited equal or larger amplitude EAG responses than their comparable saturated
      compounds. For four of the functional-group series tested, the EAG response
      amplitude was significantly greater for a particular carbon chain length, with
      responsiveness to primary alcohols and aldehydes peaking at C6, acids peaking at
      C5-6, and acetates peaking at both C5 and C8. The EAG responses to both the 2-
      and 3-position monoenic alcohols peaked at C6 and C8, while the secondary
      alcohols peaked at C7. The greatest EAG responses of all compounds tested were
      elicited by monoenic C6 alcohols and aldehydes that are constituents of the
      "general green-leaf odor" that emanates from most plants. The potential adaptive
      benefit of selective sensitivity to green-leaf volatiles is discussed in regard
      to foraging behavior of medflies. 

PMID- 24277003
TI  - Bioassays for allelopathy: Measuring treatment responses with independent
      controls.
AB  - In bioassays for allelopathy, where responses to treatments are determined in
      conjunction with responses to independent controls, statistical comparisons among
      treatments require an index which measures each treatment response (T) in
      relation to its control response (C). The most commonly used index, the treatment
      control ratio (T/C), exhibits two analytical problems. First, means ofT/C values
      are distorted upward when any of the individual values is greater than one, i.e.,
      when stimulation occurs. Second, the distribution ofT/C values may not be normal
      and homoscedastic. We provide two alternative indices of response whose means do
      not exhibit the upward distortion ofT/C means. Then, the two indices are compared
      toT/C values in an empirical test for normality and homoscedasticity on a large
      bioassay data set. Results indicate that for this data set, one of the
      alternatives,RI, is clearly superior.RI is defined as 1 - (C/T) ifT>=C and asT/C 
      1 ifT <C. 

PMID- 24277004
TI  - Upwind flight orientation to pheromone in western pine beetle tested with
      rotating wind vane traps.
AB  - In the first trap design, a rotating windvane was connected to a 30 * 30 * 30-cm
      "square box" sticky trap enclosing a synthetic pheromone source (exo-brevicomin,
      frontalin, and myrcene) at the windvane's rotation axis. A second design used the
      windvane attached to two tubular (19-cmdiam. * 30-cm) sticky traps each suspended
      120 cm from the same pheromone source and opposingly aligned "downwind" and
      "upwind" of the windvane. Significantly more beetles of each sex ofDendroctonus
      brevicomis LeC. (Coleoptera: Scolytidae) were caught on the downwind side
      compared to the upwind side of the square-box design. Even larger differences in
      catch, four times more males and 3.4 times more females, were found on the
      downwind tubular trap compared to the upwind one. The windvane trap design
      provides rigorous evidence that insects, especially bark beetles, orient upwind
      to pheromone sources (from at least 1.2 m downwind until reaching the source). 

PMID- 24277005
TI  - Novel diffusion-dilution method for release of semiochemicals: Testing pheromone
      component ratios on western pine beetle.
AB  - Each of the pheromone components of the Western pine beetle,Dendroctonus
      brevicomis LeC. (Coleoptera: Scolytidae), exo-brevicomin (E) and frontalin (F),
      were released in the forest at various ratios 0.01?1, 0.1?1, or 1?1 to a constant
      dose of the opposite component (E or F) plus the host monoterpene myrcene (M),
      which were each released at 1.5 mg/day. The components were released by a new
      method that combines the principles of chemical diffusion through a tube with
      mole percentage dilution of the chemical. Both sexes ofD. brevicomis were
      attracted similarly at comparable ratios (and release rates) of E or F and showed
      similar logarithmic relationships (r (2)=0.92?0.99). The bark beetle
      predator,Temnochila chlorodia (Mannerheim) (Coleoptera: Trogositidae) was
      apparently less sensitive to E thanD. brevicomis, being relatively less attracted
      to amounts of E equivalent to that released by 70 females, while none were
      attracted to that from seven females (while this rate still attracted significant
      numbers of conspecifics). The apparent insensitivity of bark beetles to extreme
      ratios between pheromone components in contrast to moths is discussed. The
      advantages of the diffusion-dilution method of releasing semiochemicals compared
      to previous methods of absorbents, wicks, capillary tubes, and semipermeable
      plastic membranes are also discussed. 

PMID- 24277006
TI  - Chemical correlates of rhesus monkey food choice: The influence of hydrolyzable
      tannins.
AB  - Feeding behavior was quantified of free-ranging adult rhesus monkeys in the
      Himalayan foothills of northern Pakistan. Twenty-eight food and 63 nonfood plant
      samples were collected and analyzed for tannins, alkaloids, fiber, lignin,
      protein, amino acids, total nonstructural carbohydrates, and free glucose. Most
      major foods of the rhesus were low in tannins and high in nutrients. The rhesus
      ate mainly parts of herbaceous plants, although woody plants were more abundant,
      possibly because herbs were lower in condensed tannins than woody plants. Feeding
      was negatively correlated with the astringency of tannins, ellagitannins, and
      total phenolics among all samples. Among leaves of both herbs and woody plants,
      feeding was negatively correlated with measures of hydrolyzable tannins. Total
      protein, total nonstructural carbohydrates, and water were not related to food
      choice and may not have been limiting at the site. 

PMID- 24277007
TI  - Ovipositional behavior of lesser peachtree borer in presence of host-plant
      volatiles.
AB  - Reactions of lesser peachtree borer [Synanthedon pictipes (G&R)] to volatiles of
      peach wood, either natural or chemically fractionated, were observed. Mated
      females were stimulated by and responsive to such materials and deposited
      significantly more eggs on substrates, including unnatural hosts, that had been
      treated with aqueous mixtures of bark-canker materials. Stimulation to oviposit
      occurred even when the female was blinded, indicating the presence of chemical
      cues. Natural canker-bark extracts immediately stimulated ovipostion and for a
      few hours significantly increased the number of eggs laid. However, average
      fecundity was not increased. Antennectomy did not significantly decrease response
      to volatiles by gravid females, and alternate sites of such chemoreception were
      not located. Complex mixtures derived by solvent extraction, steam distillation,
      and volatiles trapping from bark, canker, and gum all had activity. Observations
      of insect behavior in outdoor cages and also in the laboratory indicated that
      visual, chemosensory, and mechanosensory receptors are involved in host finding
      and oviposition. 

PMID- 24277008
TI  - Variability of chemosensory stimuli within honeybee (Apis mellifera) colonies:
      Differential conditioning assay for discrimination cues.
AB  - Differential training of honeybee workers using the proboscis extension reflex is
      applied to the problem of evaluating compounds that may potentially provide cues
      for kin recognition in the honeybeeApis mellifera. These cues were obtained by
      contaminating glass rods and steel needles with different materials found in the
      hive. In particular it is shown that workers discriminate between: cuticular
      waxes from different adult workers; eggs from the same and different hives;
      similar aged larvae within the same hive; and needles contaminated with the
      Nasonov gland secretions of different adult workers. It appears that some of
      these differences are due to phenotypic variation among individuals that cannot
      be directly attributed to environmental factors. 

PMID- 24277009
TI  - Influence ofHeliothis virescens sex pheromone dispensers on captures ofH. zea
      males in pheromone traps relative to distance and wind direction.
AB  - Evaluations conducted by placingHeliothis virescens (F.) sex pheromone (virelure)
      dispensers at different distances in the predominant downwind and upwind
      directions fromHeliothis zea (Boddie) pheromone traps indicated that reductions
      inH. zea male captures were greatest relative to distance when theH. zea traps
      were located downwind from the virelure dispensers than when the traps were
      located upwind. When operating traps for both species at the same site, the
      influence of virelure dispensers on captures inH. zea pheromone traps would be
      minimized by placing theH. zea traps upwind of theH. virescens traps and, if wind
      direction is variable, the traps should be spaced at least 75 m apart. 

PMID- 24277010
TI  - Response of mountain pine beetle,Dendroctonus ponderosae Hopkins, and pine
      engraver,Ips pint (SAY), to ipsdienol in southwestern British Columbia.
AB  - In bioassays conducted with walking beetles in the laboratory (S)-(+)-, (R)-(-)-,
      and (+/-)-ipsdienol were attractive alone, but reduced the attraction of both
      sexes of the mountain pine beetle,Dendroctonus ponderosae Hopkins, to extracts of
      female frass. Field trapping studies indicated that attraction ofD. ponderosae to
      a stimulus composed of myrcene +trans-verbenol +exo-brevicomin was significantly
      reduced with the addition of (+/-)- and sometimes (S)-(+/-)-ipsdienol. Thus, (S)
      (+)-ipsdienol produced by males of this species may act as an antiaggregation
      pheromone. (S)-(+)-Ips-dienol is thought to function as a repellent allomone
      against the pine engraver,Ips pini (Say), in regions whereI. pini utilizes (R)-(
      )-ipsdienol as an aggregation pheromone. However, in southwestern British
      ColumbiaI. pini was attracted to the (+/-)-ipsdienol used in field bioassays ofD.
      ponderosae, a finding consistent with the production of both enantiomers byI.
      pini in this region. When presented with the ternary semiochemical bait forD.
      ponderosae, (+/-)-ipsdienol was not attractive toI. pini. Thus, the activity of
      (S)-(+)-ipsdienol as a repellent allomone againstI. pini seems to be replaced in
      southwestern British Columbia by the inhibitory effects of myrcene,trans
      verbenol,exo-brevicomin, or some combination thereof. 

PMID- 24277011
TI  - Cardenolide content and thin-layer chromatography profiles of monarch
      butterflies,Danaus plexippus L., and their larval host-plant milkweed,Asclepias
      asperula subsp.Capricornu (woods.) woods., in north central Texas.
AB  - This paper is the second in a series on cardenolide fingerprinting of monarch
      butterflies and their host-plant milkweeds in the eastern United States.
      Spectrophotometric determinations of the gross cardenolide content ofAsclepias
      asperula plants in north central Texas indicated wide variation ranging from 341
      to 1616 MUg/0.1 g dry weight. The mean plant cardenolide concentration (886
      MUg/0.1 g) is the highest for any milkweed species on which monarch cardenolide
      profiles have been produced. Forty-one butterflies reared individually on these
      plants contained a skewed distribution of cardenolide concentrations ranging from
      231 to 515 MUg/0. 1 g dry weight with a mean of 363MUg/0.1 g. The uptake of
      cardenolide by the butterflies was independent of plant concentration, suggesting
      that saturation occurs in cardenolide sequestration by monarchs when feeding on
      cardenolide-rich host-plants. Female monarchs contained significantly greater
      mean cardenolide concentrations (339 MUg/0.1 g) than did males (320 MUg/0.1 g).
      The mean dry weight of the male butterflies (0.211 g) was significantly greater
      than the female mean (0.191) so that the mean total cardenolide contents of males
      (675 fig) and females (754 MUg) were not significantly different. Butterfly size
      was not significantly correlated to butterfly cardenolide concentration when
      differences due to sex and individual host-plant concentration were removed. Thin
      layer chrornatograms of 24 individual plant-butterfly pairs developed in two
      solvent systems resolved 22 individual spots in the plants and 15 in the
      butterflies.A. asperula plants appear to contain several relatively nonpolar
      cardenolides of the calotropagenin series which are metabolized to more polar
      derivatives in the butterflies. Quantitative evaluation of theR f values, spot
      intensities, and probabilities of occurrence in the chloroform-methanol-formamide
      TLC system produced a cardenolide fingerprint clearly distinct from those
      previously established for monarchs reared on otherAsclepias species. Our data
      support the use of fingerprints to make ecological predictions concerning larval
      host-plant utilization.A. asperula subsp.capricornu andA. viridis Walt, are the
      predominant early spring milkweeds throughout most of the south central United
      States. Cardenolide-rich monarchs reared on these two species may be instrumental
      in establishing and reinforcing visual avoidance of adults by naive predators
      throughout their spring and summer breeding cycle in eastern North America. 

PMID- 24277012
TI  - Response of generalist and specialist insects to qualitative allelochemical
      variation.
AB  - We examined the effects of a set of four biosynthetically related iridoid
      glycosides, aucubin, catalpol, loganin, and asperuloside, on larvae of a
      generalist,Lymantria dispar (Lymantriidae), the gypsy moth, and an adapted
      specialist, the buckeye,Junonia coenia (Nymphalidae). In general,L. dispar grew
      and survived significantly less well on artificial diets containing iridoid
      glycoside, compared to a control diet without iridoid glycosides. In choice
      tests, previous exposure to a diet containing iridoid glycosides caused larvae
      subsequently to prefer iridoid glycoside-containing diets even though they were
      detrimental to growth and survival. In contrast,J coenia larvae grew and survived
      better on diets with aucubin and catalpol, the two iridoid glycosides found in
      the host plantPlantago lanceolata (Plantaginaceae), than on diets with no iridoid
      glycoside or with loganin and asperuloside. The results of choice tests of diets
      with and without iridoid glycosides and between diets with different iridoid
      glycosides reflected these differences as well. These results are discussed in
      terms of (1) differences between generalists and specialists in their response to
      qualitative variation in plant allelochemical content, (2) the induction of
      feeding preferences, and (3) the evolution of qualitative allelochemical
      variation as a plant defense. 

PMID- 24277013
TI  - Effect of qualitative and quantitative variation in allelochemicals on a
      generalist insect: Iridoid glycosides and the southern armyworm.
AB  - The behavioral and physiological effects of plant allelochemicals have been
      difficult to demonstrate; it is not often clear whether the compounds are
      deterrent, toxic, or both. In this study, we compared the qualitative and
      quantitative effects of several iridoid glycosides on a generalist lepidopteran
      herbivore,Spodoptera eridania (Noctuidae). Larval growth and survivorship and
      larval preference or avoidance were measured on artificial diets containing
      different iridoid glycosides at different concentrations. We also tested the
      toxicity/deterrence of these compounds. We found that iridoid glycosides retarded
      larval growth significantly at relatively low concentrations and that they were
      usually avoided in preference tests. The toxicity/ deterrence test did not always
      reflect the results of these other tests. The merits of using a variety of
      methods for determining deterrence and/or toxicity of plant allelochemicals are
      discussed. 

PMID- 24277014
TI  - Oxygenated monoterpenes produced by yeasts, isolated fromIps typographus
      (Coleoptera: Scolytidae) and grown in phloem medium.
AB  - When yeasts associated withIps typographus beetles were grown in an aqueous
      phloem medium for two days, the main oxygenated monoterpenes produced were alpha
      terpineol and borneol. Terpinene-4-ol, myrtenol, andtrans-pinocarveol were also
      found but in lesser amounts. Of the six strains used in this study,Hansenula
      capsulata andCandida nitratophila produced the largest amounts of oxygenated
      monoterpenes. Addition of alpha-pinene to the phloem medium generally reduced the
      amounts of oxygenated monoterpenes, probably because this substance is toxic to
      all tested yeast species. OurCandida diddensii strain seemed to be particularly
      sensitive to alpha-pinene. None of the yeast strains producedcis-verbenol,trans
      verbenol, or verbenone from the medium or from added alpha-pinene. 

PMID- 24277015
TI  - Use of predator odors as repellents to reduce feeding damage by herbivores : III.
      Montane and meadow voles (Microtus montanus andMicrotus pennsylvanicus).
AB  - This study investigated the influence of the major anal-gland compounds from the
      stoat (Mustela erminea) and fecal and urine compounds from the red fox (Vulpes
      vulpes) in generating an avoidance response by montane voles (Microtus montanus),
      as well as suppressing feeding by montane and meadow (M. pennsylvanicus) voles on
      apple trees in orchards. In trap bioassays, a 1?1 mixture of 2-propylthietane and
      3-propyl-1,2-dithiolane significantly reduced vole captures. Other mixtures of
      stoat compounds reduced the number of new voles captured but not total
      individuals. 2,5-Dihydro-2,4,5-trimethylthiazoline, a component of fox feces,
      significantly reduced vole captures in one of two bioassays. Deer mice
      (Peromyscus maniculatus) did not show a negative response to any predator odor.
      In overwinter field bioassays, mixtures of 2-propylthietane and 3-propyl-1,2
      dithiolane clearly reduced vole feeding on apple trees in four test blocks. 2,5
      Dihydro-2,4,5-trimethylthiazoline and a synthetic fox urine mixture also
      significantly reduced vole attack in respective orchard blocks. Similarly, the
      intensity of vole feeding, in terms of amount of bark and vascular tissues
      removed from trees, was reduced by 60% to 97% in predator odor treatments
      compared with the control. Our study reports the first long-term (four to five
      months) use of synthetic semiochemicals as area repellents for crop protection
      from vole feeding damage. 

PMID- 24277016
TI  - Use of predator odors as repellents to reduce feeding damage by herbivores : IV.
      Northern pocket gophers (Thomomys talpoides).
AB  - This study investigated the influence of the major anal-gland compounds from the
      stoat (Mustela erminea) and ferret (M. putorius) in generating an avoidance
      response by northern pocket gophers (Thomomys talpoides) in tree fruit orchards
      in the Okanagan Valley of British Columbia, Canada. A secondary objective
      assessed the impact of additional predator odors on gopher avoidance behavior in
      laboratory bioassays. In field bioassays, a 1: 1 mixture of 2-propylthietane and
      3-propyl-1,2-dithiolane, as well as 3,3-dimethyl-1,2-dithiolane, placed in gopher
      burrows did not reduce the number of gophers colonizing treatment versus control
      grids in orchard blocks. However, these predator gophers did dramatically alter
      the distribution of gophers. Significantly more gophers were captured at
      perimeter than nonperimeter trap stations on treatment versus control grids in
      two of three orchards. In all orchards, significantly more gophers were captured
      at perimeter stations after the predator odors had been placed in burrows than
      prior to the start of the experiment. Gophers clearly avoided 2,5-dihydro-2,4,5
      trimethylthiazoline, a component of fox (Vulpes vulpes) feces, but did not avoid
      2,2-dimethylthietane from the mink (M. vison) or 3-methyl-3-butenyl methyl
      sulfide from fox urine in laboratory bioassays. Poor avoidance was also recorded
      for 3,3-dimethyl-1,2-dithiolane, although this may be due to the state of
      polymerization of this compound. An improved formulation is required to dispense
      these semiochemicals in controlled-release devices within orchards and other
      forest-agricultural areas. 

PMID- 24277017
TI  - Components of female sex pheromone ofEoreuma loftini Dyar.
AB  - Three chemicals isolated from ovipositor rinses of virgin femaleEoreuma loftini
      Dyar (Mexican rice borer) moths were identified as (Z)-13-octadecenyl acetate
      (I), (Z)-11-hexadecenyl acetate (II), and (Z)-13-octadecenal (III) in the
      approximate ratio 8?1?1.3, respectively. Preliminary tests indicate that in
      laboratory bioassays, these chemicals in the above ratio induce the same activity
      response as heptane extracts of rice borer ovipositors. Only one combination of
      two chemicals (I and III, 6.2?1 ratio) elicited a similar response. Individual
      chemicals elicited no response. In field tests, the average number of male rice
      borer moths caught per night over a five-night period was the same in traps
      baited with 200-600-MUg quantities of the 8?1?1.3 ratio of chemicals dispensed
      from strips of filter paper as with traps baited with virgin females. The two
      component mixture (I and III, 6.2?1 ratio) was not active in the field. 

PMID- 24277018
TI  - Evidence for occurrence of mounting sex pheromone on body surface of
      femaleDermacentor variabilis (Say) AndDermacentor andersoni (Stiles) (Acari:
      Ixodidae).
AB  - MaleDermacentor variabilis andD. andersoni respond to an unknown chemical or
      chemicals present on the body surfaces of partially engorged conspecific female
      ticks. Following contact, the males mount the females and apply their mouthparts
      and legs against the female dorsal body surface. Then, the males turn with these
      appendages still in close contact and crawl to the female's venter, whereupon
      they locate the gonopore, probe the vulva, and copulate. Similar responses are
      elicited by heterospecific as well as conspecific females. However, the response
      is lost when the female cuticle is cleaned (delipidized) with organic solvents.
      It can be restored by applying hexane extracts prepared from female cuticle to
      the previously cleaned females. Males do not use surface texture as the primary
      stimulus for mate recognition. Male ticks also respond to hexane extracts applied
      to spherical inanimate objects, ("dummy" female), suggesting that a chemical or
      chemicals soluble in organic solvents has been transferred to these objects.
      These findings suggest the existence of a previously undescribed pheromone, the
      mounting sex pheromone (MSP). This contact sex pheromone enables males excited
      and attracted by 2,6-dichlorophenol to identify the female as a potential mating
      partner. The MSP is the second in the series of three sex pheromones guiding the
      hierarchy of behavioral responses which constitute tick courtship behavior. 

PMID- 24277019
TI  - Antimicrobial activity of solithromycin against clinical isolates of Legionella
      pneumophila serogroup 1.
AB  - The activity of solithromycin was evaluated against clinical Legionella
      pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada,
      from 1980 to 2011. Its in vitro activity was compared to that of azithromycin
      (AZM) using the broth microdilution method. Solithromycin had a MIC50 of <=0.015
      MUg/ml and a MIC90 of 0.031 MUg/ml, making its activity at least 8-fold to 32
      fold higher than that of AZM (MIC50 and MIC90, 0.125 MUg/ml and 1 MUg/ml,
      respectively). Ninety-nine percent of the isolates had MICs for solithromycin
      ranging from <=0.015 MUg/ml to 0.031 MUg/ml, whereas 83.6% of the isolates showed
      MICs for AZM ranging from 0.062 MUg/ml to 0.25 MUg/ml. Interestingly, 96.7% (30
      out of 31 clinical isolates) identified with higher AZM MICs (0.5 MUg/ml to 2
      MUg/ml) belonged to the clinically prevalent sequence type 1. To investigate the
      intracellular activity of solithromycin, in vitro invasion assays were also
      performed against a subset of representative Lp1 isolates internalized within
      human lung epithelial cells. Solithromycin and AZM both inhibited growth of all
      intracellular Lp1 isolates at 1* or 8* MICs, displaying bacteriostatic effects,
      as would be expected with protein synthesis inhibitor rather than bactericidal
      activity. Solithromycin demonstrated the highest in vitro and intracellular
      potency against all Lp1 isolates compared to AZM. Given the rapid spread of
      resistance mechanisms among respiratory pathogens and the reported treatment
      failures in legionellosis, the development of this new fluoroketolide, already in
      phase 3 oral clinical studies, constitutes a promising alternative option for the
      treatment of legionellosis. 

PMID- 24277020
TI  - In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for
      treatment of Clostridium difficile infections.
AB  - Clostridium difficile is a leading cause of health care-associated diarrhea with
      significant morbidity and mortality, and new options for the treatment of C.
      difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone
      type antibiotic that is currently in clinical development for treatment of CDAD.
      Here, we report the in vitro and in vivo antibacterial evaluation of cadazolid
      against C. difficile. Cadazolid showed potent in vitro activity against C.
      difficile with a MIC range of 0.125 to 0.5 MUg/ml, including strains resistant to
      linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid
      showed a bactericidal effect against C. difficile isolates, with >99.9% killing
      in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole
      and vancomycin, cadazolid strongly inhibited de novo toxin A and B formation in
      stationary-phase cultures of toxigenic C. difficile. Cadazolid also inhibited C.
      difficile spore formation substantially at growth-inhibitory concentrations. In
      the hamster and mouse models for CDAD, cadazolid was active, conferring full
      protection from diarrhea and death with a potency similar to that of vancomycin.
      These findings support further investigations of cadazolid for the treatment of
      CDAD. 

PMID- 24277021
TI  - Pharmacokinetic-pharmacodynamic target attainment analyses to evaluate in vitro
      susceptibility test interpretive criteria for ceftaroline against Staphylococcus
      aureus and Streptococcus pneumoniae.
AB  - To provide support for in vitro susceptibility test interpretive criteria
      decisions for ceftaroline against Staphylococcus aureus and Streptococcus
      pneumoniae, as well as dose adjustment recommendations for renal impairment,
      pharmacokinetic-pharmacodynamic (PK-PD) target attainment was evaluated for
      simulated patients administered intravenous (i.v.) ceftaroline fosamil at 600 mg
      twice daily (q12h) and simulated patients with renal impairment administered
      various dosing regimens. Using a previously developed population PK model, Monte
      Carlo simulation was used to generate ceftaroline plasma concentration profiles
      for simulated patients with normal renal function or mild, moderate, or severe
      renal impairment. Using these profiles, the percentage of time during the dosing
      interval that free-drug concentrations remained above the MIC (f%T>MIC) for
      ceftaroline at steady state was calculated. Percentages of simulated patients
      achieving f %T>MIC targets for S. aureus and S. pneumoniae based on murine
      infection models were calculated by MIC. At MICs of 2 mg/liter for S. aureus and
      1 mg/liter for S. pneumoniae, the percentages of simulated patients with normal
      renal function and mild renal impairment following administration of ceftaroline
      fosamil at 600 mg q12h, moderate renal impairment following administration of
      ceftaroline fosamil at 400 mg q12h, and severe renal impairment following
      administration of ceftaroline fosamil at 300 mg q12h achieving f %T>MIC targets
      (>=26 for S. aureus and >=44 for S. pneumoniae) exceeded 90%. The results of
      these analyses, which suggested that in vitro susceptibility test interpretive
      criteria defining susceptible could be as high as MICs of <=2 and <=1 mg/liter
      for ceftaroline against S. aureus and S. pneumoniae, respectively, provide
      support for current FDA and CLSI criteria, which define susceptible as MICs of 1
      and 0.5 mg/liter, respectively. Recommendations for dose adjustments for patients
      with renal impairment were also supported by the results of these analyses. 

PMID- 24277022
TI  - In vitro pharmacodynamics of polymyxin B and tigecycline alone and in combination
      against carbapenem-resistant Acinetobacter baumannii.
AB  - Carbapenem-resistant Acinetobacter baumannii is increasing in prevalence.
      Polymyxin B and tigecycline are among the most active antibiotics used against
      this pathogen in vitro. Past in vitro studies, however, neglected the importance
      of simulating exposures observed in humans to determine their antibacterial
      effects. In this study, four carbapenem-resistant A. baumannii isolates were
      evaluated using an in vitro pharmacodynamic model. Free-drug exposures using 1
      mg/kg of body weight of polymyxin B every 12 h (q12h), 100 and 200 mg tigecycline
      q12h, and the combination of these regimens were simulated. The microbiological
      responses to these treatments were measured by the change in log10 CFU/ml over 24
      h and the area under the bacterial killing and regrowth curve (AUBC). Resistance
      was assessed by a population analysis profile (PAP) conducted after 24 h of
      treatment. Polymyxin B achieved a reduction on the order of -2.05 +/- 0.68 log10
      CFU/ml against these A. baumannii isolates, while all isolates grew to control
      levels with tigecycline monotherapy. Combination therapy with polymyxin B plus
      200 mg tigecycline q12h achieved a greater reduction in bacterial density than
      did therapy with polymyxin B alone (-3.31 +/- 0.71 versus -2.05 +/- 0.68 log10
      CFU/ml, P < 0.001) but not significantly different than combination therapy with
      100 mg tigecycline q12h (-2.45 +/- 1.00 log10 CFU/ml, P = 0.370). Likewise,
      combination therapy with polymyxin B plus 200 mg tigecycline q12h significantly
      reduced the AUBC compared to that with polymyxin B alone (62.8 +/- 8.9 versus
      79.4 +/- 10.5 log10 CFU/ml, P < 0.05). No changes in the PAP from baseline were
      observed for either antibiotic alone. In this study, combination therapy with
      simulated exposures of polymyxin B and tigecycline at an aggressive dose of 200
      mg q12h produced synergistic or additive effects on humans against these
      multidrug-resistant A. baumannii strains. 

PMID- 24277023
TI  - Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab
      PCR assay for MRSA pneumonia.
AB  - Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is associated
      with poor outcomes and frequently merits empirical antibiotic consideration
      despite its relatively low incidence. Nasal colonization with MRSA is associated
      with clinical MRSA infection and can be reliably detected using the nasal swab
      PCR assay. In this study, we evaluated the performance of the nasal swab MRSA PCR
      in predicting MRSA pneumonia. A retrospective cohort study was performed in a
      tertiary care center from January 2009 to July 2011. All patients with confirmed
      pneumonia who had both a nasal swab MRSA PCR test and a bacterial culture within
      predefined time intervals were included in the study. These data were used to
      calculate sensitivity, specificity, positive predictive value, and negative
      predictive value for clinically confirmed MRSA pneumonia. Four hundred thirty
      five patients met inclusion criteria. The majority of cases were classified as
      either health care-associated (HCAP) (54.7%) or community-acquired (CAP) (34%)
      pneumonia. MRSA nasal PCR was positive in 62 (14.3%) cases. MRSA pneumonia was
      confirmed by culture in 25 (5.7%) cases. The MRSA PCR assay demonstrated 88.0%
      sensitivity and 90.1% specificity, with a positive predictive value of 35.4% and
      a negative predictive value of 99.2%. In patients with pneumonia, the MRSA PCR
      nasal swab has a poor positive predictive value but an excellent negative
      predictive value for MRSA pneumonia in populations with low MRSA pneumonia
      incidence. In cases of culture-negative pneumonia where initial empirical
      antibiotics include an MRSA-active agent, a negative MRSA PCR swab can be
      reasonably used to guide antibiotic de-escalation. 

PMID- 24277024
TI  - Nutritional control of antibiotic resistance via an interface between the
      phosphotransferase system and a two-component signaling system.
AB  - Enterococci are ubiquitous inhabitants of the gastrointestinal (GI) tract.
      However, antibiotic-resistant enterococci are also major causes of hospital
      acquired infections. Enterococci are intrinsically resistant to cephalosporins,
      enabling growth to abnormally high densities in the GI tract in patients during
      cephalosporin therapy, thereby promoting dissemination to other sites where they
      cause infection. Despite its importance, many questions about the underlying
      basis for cephalosporin resistance remain. A specific two-component signaling
      system, composed of the CroS sensor kinase and its cognate response regulator
      (CroR), is required for cephalosporin resistance in Enterococcus faecalis, but
      little is known about the factors that control this signaling system to modulate
      resistance. To explore the signaling network in which CroR participates to
      influence cephalosporin resistance, we employed a protein fragment
      complementation assay to detect protein-protein interactions in E. faecalis
      cells, revealing a previously unknown association of CroR with the HPr protein of
      the phosphotransferase system (PTS) responsible for carbohydrate uptake and
      catabolite control of gene expression. Genetic and physiological analyses
      indicate that association with HPr restricts the ability of CroR to promote
      cephalosporin resistance and gene expression in a nutrient-dependent manner.
      Mutational analysis suggests that the interface used by HPr to associate with
      CroR is distinct from the interface used to associate with other cellular
      partners. Our results define a physical and functional connection between a
      critical nutrient-responsive signaling system (the PTS) and a two-component
      signaling system that drives antibiotic resistance in E. faecalis, and they
      suggest a general strategy by which bacteria can integrate their nutritional
      status with diverse environmental stimuli. 

PMID- 24277025
TI  - Activity of ceftolozane-tazobactam against a broad spectrum of recent clinical
      anaerobic isolates.
AB  - We evaluated in vitro activity of ceftolozane-tazobactam (TOL-TAZ), formerly CXA
      201, against recent clinical anaerobic isolates with emphasis on the Bacteroides
      fragilis group. Ceftolozane-tazobactam showed good activity against B. fragilis
      species and intermediate to limited activity against other species of
      Bacteroides. Ceftolozane-tazobactam showed very good activity against Prevotella
      spp., Fusobacterium spp., and Propionibacterium spp., varying activities against
      Gram-positive cocci, and limited activity against Clostridium spp. 

PMID- 24277026
TI  - Members of the conserved DedA family are likely membrane transporters and are
      required for drug resistance in Escherichia coli.
AB  - Bacterial resistance to antibiotics and biocides is an increasing public health
      problem. Genes encoding integral membrane proteins belonging to the DedA family
      are present in most bacterial genomes, including Escherichia coli. An E. coli
      strain lacking partially redundant DedA family genes yqjA and yghB (strain BC202)
      displays temperature sensitivity and cell division defects. These phenotypes can
      be corrected by overexpression of mdfA, an Na(+)-K(+)/H(+) antiporter of the
      major facilitator superfamily. We show that BC202 is hypersensitive to several
      biocides and cationic compounds that are known substrates of several multidrug
      resistance transporters, including MdfA, EmrE, and AcrB. The introduction of
      deletions of genes encoding these drug transporters into BC202 results in
      additional sensitivity. Expression of wild-type yghB or yqjA can restore drug
      resistance, but this is eliminated upon mutation of two membrane-embedded acidic
      amino acids (E39 or D51 in either protein). This dependence upon membrane
      embedded acidic amino acids is a hallmark of proton-dependent antiporters.
      Overexpression of mdfA in BC202 or artificially restoring proton motive force
      (PMF) restores wild-type resistance to substrates of MdfA as well as other drug
      resistance transporters such as EmrE and AcrAB. These results suggest that YqjA
      and YghB may be membrane transporters required for PMF-dependent drug efflux in
      E. coli. 

PMID- 24277027
TI  - Multicenter study of anidulafungin and micafungin MIC distributions and
      epidemiological cutoff values for eight Candida species and the CLSI M27-A3 broth
      microdilution method.
AB  - Since epidemiological cutoff values (ECVs) using CLSI MICs from multiple
      laboratories are not available for Candida spp. and the echinocandins, we
      established ECVs for anidulafungin and micafungin on the basis of wild-type (WT)
      MIC distributions (for organisms in a species-drug combination with no detectable
      acquired resistance mechanisms) for 8,210 Candida albicans, 3,102 C. glabrata,
      3,976 C. parapsilosis, 2,042 C. tropicalis, 617 C. krusei, 258 C. lusitaniae, 234
      C. guilliermondii, and 131 C. dubliniensis isolates. CLSI broth microdilution MIC
      data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and
      the United States were aggregated to statistically define ECVs. ECVs encompassing
      97.5% of the statistically modeled population for anidulafungin and micafungin
      were, respectively, 0.12 and 0.03 MUg/ml for C. albicans, 0.12 and 0.03 MUg/ml
      for C. glabrata, 8 and 4 MUg/ml for C. parapsilosis, 0.12 and 0.06 MUg/ml for C.
      tropicalis, 0.25 and 0.25 MUg/ml for C. krusei, 1 and 0.5 MUg/ml for C.
      lusitaniae, 8 and 2 MUg/ml for C. guilliermondii, and 0.12 and 0.12 MUg/ml for C.
      dubliniensis. Previously reported single and multicenter ECVs defined in the
      present study were quite similar or within 1 2-fold dilution of each other. For a
      collection of 230 WT isolates (no fks mutations) and 51 isolates with fks
      mutations, the species-specific ECVs for anidulafungin and micafungin correctly
      classified 47 (92.2%) and 51 (100%) of the fks mutants, respectively, as non-WT
      strains. These ECVs may aid in detecting non-WT isolates with reduced
      susceptibility to anidulafungin and micafungin due to fks mutations. 

PMID- 24277028
TI  - Potential of host defense peptide prodrugs as neutrophil elastase-dependent anti
      infective agents for cystic fibrosis.
AB  - Host defense peptides (HDPs) are short antimicrobial peptides of the innate
      immune system. Deficiencies in HDPs contribute to enhanced susceptibility to
      infections, e.g., in cystic fibrosis (CF). Exogenous HDPs can compensate for
      these deficiencies, but their development as antimicrobials is limited by
      cytotoxicity. Three HDP prodrugs were designed so their net positive charge is
      masked by a promoiety containing a substrate for the enzyme neutrophil elastase
      (NE). This approach can confine activation to sites with high NE levels. Enzyme
      labile peptides were synthesized, and their activation was investigated using
      purified NE. Susceptibilities of Pseudomonas aeruginosa to parent and prodrug
      peptides in the presence and absence of NE-rich CF human bronchoalveolar lavage
      (BAL) fluid and different NaCl concentrations were compared. The effect of the
      HDP promoiety on cytotoxicity was determined with cystic fibrosis bronchial
      epithelial (CFBE41o-) cells. NE in CF BAL fluids activated the HDP prodrugs,
      restoring bactericidal activity against reference and clinical isolates of P.
      aeruginosa. However, activation also required the addition of 300 mM NaCl. Under
      these conditions, the bactericidal activity levels of the HDP prodrugs differed,
      with pro-P18 demonstrating the greatest activity (90% to 100% of that of the
      parent, P18, at 6.25 MUg/ml). Cytotoxic effects on CFBE41o- cells were reduced by
      the addition of the promoiety to HDPs. We demonstrate here for the first time the
      selective activation of novel HDP prodrugs by a host disease-associated enzyme at
      in vivo concentrations of the CF lung. This approach may lead to the development
      of novel therapeutic agents with low toxicity that are active under the
      challenging conditions of the CF lung. 

PMID- 24277029
TI  - Phosphate-containing polyethylene glycol polymers prevent lethal sepsis by
      multidrug-resistant pathogens.
AB  - Antibiotic resistance among highly pathogenic strains of bacteria and fungi is a
      growing concern in the face of the ability to sustain life during critical
      illness with advancing medical interventions. The longer patients remain
      critically ill, the more likely they are to become colonized by multidrug
      resistant (MDR) pathogens. The human gastrointestinal tract is the primary site
      of colonization of many MDR pathogens and is a major source of life-threatening
      infections due to these microorganisms. Eradication measures to sterilize the gut
      are difficult if not impossible and carry the risk of further antibiotic
      resistance. Here, we present a strategy to contain rather than eliminate MDR
      pathogens by using an agent that interferes with the ability of colonizing
      pathogens to express virulence in response to host-derived and local
      environmental factors. The antivirulence agent is a phosphorylated triblock high
      molecular-weight polymer (here termed Pi-PEG 15-20) that exploits the known
      properties of phosphate (Pi) and polyethylene glycol 15-20 (PEG 15-20) to
      suppress microbial virulence and protect the integrity of the intestinal
      epithelium. The compound is nonmicrobiocidal and appears to be highly effective
      when tested both in vitro and in vivo. Structure functional analyses suggest that
      the hydrophobic bis-aromatic moiety at the polymer center is of particular
      importance to the biological function of Pi-PEG 15-20, beyond its phosphate
      content. Animal studies demonstrate that Pi-PEG prevents mortality in mice
      inoculated with multiple highly virulent pathogenic organisms from hospitalized
      patients in association with preservation of the core microbiome. 

PMID- 24277030
TI  - In vitro combination of anti-cytomegalovirus compounds acting through different
      targets: role of the slope parameter and insights into mechanisms of Action.
AB  - Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the
      viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV
      resistant strains emerge, alternative therapies are extremely limited and are
      associated with significant toxicities. Combination of anti-CMV agents that act
      on different targets or stages of virus replication has not been well studied,
      mostly because of the limited number of anti-CMV agents. We report our
      investigation of combinations of agents that inhibit CMV by targeting the viral
      DNA polymerase, cellular kinases, or other cell/virus mechanisms yet to be
      discovered. The selected compounds differed by the slopes of their dose-response
      curve: compounds with a slope of 1 (GCV) representing one target or
      noncooperativity and compounds with high slopes indicating positive
      cooperativity. Analysis of anti-CMV drug combinations using the Bliss model
      (which accounts for the slope parameter) distinguished between combinations with
      synergistic, antagonistic, and additive activities. The combination of GCV and
      foscarnet was slightly synergistic; strong synergism was found when GCV was used
      with artemisinin-derived monomers or dimers or the MEK inhibitor U0126. The
      combination of GCV and cardiac glycosides (digoxin, digitoxin, and ouabain) was
      additive. The monomeric artemisinin artesunate was synergistic when combined with
      U0126 or the multikinase inhibitor sunitinib. However, the combination of
      artemisinin-derived dimers (molecular weights, 606 and 838) and U0126 or
      sunitinib was antagonistic. These results demonstrate that members of a specific
      drug class show similar patterns of combination with GCV and that the slope
      parameter plays an important role in the evaluation of drug combinations. Lastly,
      antagonism between different classes of CMV inhibitors may assist in target
      identification and improve the understanding of CMV inhibition by novel
      compounds. 

PMID- 24277031
TI  - Contribution of beta-lactamases and porin proteins OmpK35 and OmpK36 to
      carbapenem resistance in clinical isolates of KPC-2-producing Klebsiella
      pneumoniae.
AB  - Fifty-seven carbapenem-resistant Klebsiella pneumoniae isolates belonging to ST11
      (50 isolates), ST423 (5 isolates), and two other sequence types were studied. All
      were positive for blaKPC-2, blaTEM-1, and blaCTX-M-14. SDS-PAGE analysis of six
      representative isolates demonstrated varied porin expression. Nevertheless, when
      blaKPC-2 was deleted, carbapenem resistance was markedly reduced. Additionally,
      SHV-12, DHA-1, and/or VIM-1 appeared to contribute to accessory carbapenemase
      activity. In contrast, OmpK35 and/or OmpK36 deficiency seemed to serve only as a
      minor cooperative factor. 

PMID- 24277032
TI  - Function of the loading module in CorI and of the O-methyltransferase CorH in
      vinyl carbamate biosynthesis of the antibiotic corallopyronin A.
AB  - Corallopyronin A is a promising in vivo active antibiotic, currently undergoing
      preclinical evaluation. This myxobacterial compound interferes with a newly
      identified drug target site, i.e., the switch region of the bacterial DNA
      dependent RNA-polymerase (RNAP). Since this target site differs from that of
      known RNAP inhibitors such as the rifamycins, corallopyronin A shows no cross
      resistance with other antibacterial agents. Corallopyronin A is a polyketide
      synthase- and nonribosomal peptide synthetase-derived molecule whose structure
      and biosynthesis is distinguished by several peculiarities, such as the unusual
      vinyl carbamate functionality whose formation involves carbonic acid as an
      unprecedented C1-starter unit. Using in vitro experiments the nature of this
      starter molecule was revealed to be the methyl ester of carbonic acid.
      Biochemical investigations showed that methylation of carbonic acid is performed
      by the O-methyltransferase CorH. These experiments shed light on the biosynthesis
      of the Eastern chain of alpha-pyrone antibiotics such as corallopyronin A. 

PMID- 24277033
TI  - Incidence density of invasive fungal infections during primary antifungal
      prophylaxis in newly diagnosed acute myeloid leukemia patients in a tertiary
      cancer center, 2009 to 2011.
AB  - Although primary antifungal prophylaxis (PAP) is routinely administered in
      patients with acute myeloid leukemia (AML) during remission-induction and
      consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal
      infections (IFIs) is not well described. We retrospectively analyzed the
      incidence of IFIs in 152 patients with AML who had been admitted to a tertiary
      cancer center between August 2009 and March 2011 and received PAP within 120 days
      after first remission-induction chemotherapy. We excluded patients who had
      undergone stem cell transplantation. Patients received a PAP drug with anti
      Aspergillus activity during 72% (7,660/10,572) of prophylaxis-days. The incidence
      of documented IFIs (definite or probable according to revised European
      Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000
      prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds
      were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus
      0.4/1,000 prophylaxis-days; P = 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000
      prophylaxis-days, respectively) was associated with higher rates of documented
      IFIs than anti-Aspergillus azoles (voriconazole or posaconazole) (2.4 and
      1.1/1,000 prophylaxis-days, respectively) at both 42 days (P = 0.03) and 120 days
      (P < 0.0001) after first remission-induction chemotherapy. The incidence of
      overall (documented and presumed) IFIs (P < 0.001), documented IFIs (P < 0.01),
      and empirical antifungal therapies (P < 0.0001) was higher during the first 42
      days than after day 42. Despite the broad use of PAP with anti-Aspergillus
      activity, IFIs, especially molds, remain a significant cause of morbidity and
      mortality in AML patients, predominantly during the remission-induction phase.
      Patients receiving echinocandin-based PAP experienced higher rates of IFIs than
      did those receiving anti-Aspergillus azoles. 

PMID- 24277034
TI  - Even apparently insignificant chemical deviations among bioequivalent generic
      antibiotics can lead to therapeutic nonequivalence: the case of meropenem.
AB  - Several studies with animal models have demonstrated that bioequivalence of
      generic products of antibiotics like vancomycin, as currently defined, do not
      guarantee therapeutic equivalence. However, the amounts and characteristics of
      impurities and degradation products in these formulations do not violate the
      requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data
      with three generic products of meropenem that help in understanding how these
      apparently insignificant chemical differences affect the in vivo efficacy.
      Meropenem generics were compared with the innovator in vitro by microbiological
      assay, susceptibility testing, and liquid chromatography/mass spectrometry
      (LC/MS) analysis and in vivo with the neutropenic guinea pig soleus infection
      model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa),
      brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding
      the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to
      the carbapenem. We found that the concentration and potency of the active
      pharmaceutical ingredient, in vitro susceptibility testing, and mouse
      pharmacokinetics were identical for all products; however, two generics differed
      significantly from the innovator in the guinea pig and mouse models, while the
      third generic was therapeutically equivalent under all conditions. Trisodium
      adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis
      and less stable at room temperature, explaining its therapeutic nonequivalence.
      We conclude that the therapeutic nonequivalence of generic products of meropenem
      is due to greater susceptibility to DHP-I hydrolysis. These failing generics are
      compliant with USP requirements and would remain undetectable under current
      regulations. 

PMID- 24277035
TI  - Investigations of the mode of action and resistance development of cadazolid, a
      new antibiotic for treatment of Clostridium difficile infections.
AB  - Cadazolid is a new oxazolidinone-type antibiotic currently in clinical
      development for the treatment of Clostridium difficile-associated diarrhea. Here,
      we report investigations on the mode of action and the propensity for spontaneous
      resistance development in C. difficile strains. Macromolecular labeling
      experiments indicated that cadazolid acts as a potent inhibitor of protein
      synthesis, while inhibition of DNA synthesis was also observed, albeit only at
      substantially higher concentrations of the drug. Strong inhibition of protein
      synthesis was also obtained in strains resistant to linezolid, in agreement with
      low MICs against such strains. Inhibition of protein synthesis was confirmed in
      coupled transcription/translation assays using extracts from different C.
      difficile strains, including strains resistant to linezolid, while inhibitory
      effects in DNA topoisomerase assays were weak or not detectable under the assay
      conditions. Spontaneous resistance frequencies of cadazolid were low in all
      strains tested (generally <10(-10) at 2* to 4* the MIC), and in multiple-passage
      experiments (up to 13 passages) MICs did not significantly increase. Furthermore,
      no cross-resistance was observed, as cadazolid retained potent activity against
      strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new
      antibiotic fidaxomicin. In conclusion, the data presented here indicate that
      cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition
      of DNA synthesis as a potential second mode of action, and suggest a low
      potential for spontaneous resistance development. 

PMID- 24277036
TI  - Evaluation of vancomycin in combination with piperacillin-tazobactam or oxacillin
      against clinical methicillin-resistant Staphylococcus aureus Isolates and
      vancomycin-intermediate S. aureus isolates in vitro.
AB  - Vancomycin with piperacillin-tazobactam is used as empirical therapy for
      critically ill patients. Studies of this combination against methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus
      (VISA) are limited, but beta-lactams in combination with vancomycin have shown
      synergistic activity against MRSA and VISA. The goal of this study was to
      evaluate whether piperacillin-tazobactam and vancomycin were synergistic against
      MRSA and VISA in vitro. Bloodstream MRSA (n = 20) and VISA (n = 4) strains were
      selected. In vitro antimicrobial activities of piperacillin-tazobactam and
      oxacillin were evaluated by disk diffusion, and MICs were determined by Etest
      using Muller-Hinton agar with and without vancomycin at one-half the MIC. Time
      kill studies evaluated 14 MRSA and all 4 VISA isolates using piperacillin
      tazobactam at 300/35 mg/liter or oxacillin at 40 mg/liter alone and with
      vancomycin at one-half the MIC. Mean zones of inhibition for piperacillin
      tazobactam and oxacillin increased with vancomycin against MRSA and VISA (P <
      0.001 for all), and the MIC90 decreased with vancomycin against MRSA and VISA to
      values meeting susceptibility criteria for S. aureus (P < 0.001 for both
      antibiotics against MRSA). In MRSA time-kill studies, the mean 24-h reductions in
      inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin,
      and oxacillin with vancomycin were 3.53, 3.69, and 2.62 log10 CFU/ml,
      respectively. The mean 24-h reductions in VISA inoculum for piperacillin
      tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with
      vancomycin were 2.85, 2.93, and 3.45 log10 CFU/ml, respectively. Vancomycin with
      piperacillin-tazobactam or oxacillin demonstrated synergistic activity against
      MRSA and VISA. The clinical implications of these combinations against MRSA and
      VISA should be investigated. 

PMID- 24277037
TI  - Clinical experience of colistin-glycopeptide combination in critically ill
      patients infected with Gram-negative bacteria.
AB  - A colistin-glycopeptide combination (CGC) has been shown in vitro to be
      synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB),
      especially Acinetobacter baumannii, and to prevent further resistance. However,
      clinical data are lacking. We carried out a retrospective multicenter study of
      patients hospitalized in intensive care units (ICUs) who received colistin for
      GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30
      day mortality after treatment onset among patients treated with and without CGC
      for >=48 h. Of the 184 patients treated with colistin, GNB infection was
      documented for 166. The main causative agents were MDR A. baumannii (59.6%), MDR
      Pseudomonas aeruginosa (18.7%), and carbapenem-resistant Klebsiella pneumoniae
      (14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was
      documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients
      treated with and without CGC showed significant differences for respiratory
      failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus
      71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2%
      versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and
      30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who
      survived for >=5 days after treatment onset showed that the Charlson index
      (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P = 0.001)
      and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P = 0.01) were
      independent predictors of 30-day mortality, whereas receiving CGC for >=5 days
      was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03). We found that
      CGC was not associated with higher nephrotoxicity and was a protective factor for
      mortality if administered for >=5 days. 

PMID- 24277038
TI  - Novel cell-based hepatitis C virus infection assay for quantitative high
      throughput screening of anti-hepatitis C virus compounds.
AB  - Therapy for hepatitis C virus (HCV) infection has advanced with the recent
      approval of direct-acting antivirals in combination with peginterferon and
      ribavirin. New antivirals with novel targets are still needed to further improve
      the treatment of hepatitis C. Previously reported screening methods for HCV
      inhibitors either are limited to a virus-specific function or apply a screening
      method at a single dose, which usually leads to high false-positive or -negative
      rates. We developed a quantitative high-throughput screening (qHTS) assay
      platform with a cell-based HCV infection system. This highly sensitive assay can
      be miniaturized to a 1,536-well format for screening of large chemical libraries.
      All candidates are screened over a 7-concentration dose range to give EC50s
      (compound concentrations at 50% efficacy) and dose-response curves. Using this
      assay format, we screened a library of pharmacologically active compounds
      (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and
      cytotoxicity, 22 compounds with adequate curves and EC50s of <10 MUM were
      selected for validation. In two additional independent assays, 17 of them
      demonstrated specific inhibition of HCV infection. Ten potential candidates with
      efficacies of >70% and CC50s (compound concentrations at 50% cytotoxicity) of <30
      MUM from these validated hits were characterized for their target stages in the
      HCV replication cycle. In this screen, we identified both known and novel hits
      with diverse structural and functional features targeting various stages of the
      HCV replication cycle. The pilot screen demonstrates that this assay system is
      highly robust and effective in identifying novel HCV inhibitors and that it can
      be readily applied to large-scale screening of small-molecule libraries. 

PMID- 24277039
TI  - Factors associated with treatment failure in vertebral osteomyelitis requiring
      spinal instrumentation.
AB  - Patients with vertebral osteomyelitis may require instrumentation for spinal
      stabilization. Determining the optimal duration and type of antimicrobial therapy
      for these patients is challenging. The aim of this study was to examine risk
      factors for treatment failure, in particular antimicrobial duration, in a cohort
      of patients requiring spinal instrumentation for vertebral osteomyelitis. We
      conducted a retrospective cohort study of all patients with vertebral
      osteomyelitis who had spinal instrumentation between January 2002 and January
      2012 at the University of Maryland Medical Center. The primary outcome measure
      was treatment failure >4 weeks postoperatively. We identified 131 patients with
      vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks
      of follow-up and were included in the primary analysis. Treatment failure
      occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery.
      Among patients who failed therapy, 20 of 22 failed within 1 year of surgery.
      Cervical and thoracic infection sites and the presence of negative cultures were
      associated with fewer treatment failures. Addition of rifampin and the use of
      chronic suppressive antimicrobials did not affect treatment failure rate. Twenty
      three percent of patients with spinal instrumentation for vertebral osteomyelitis
      experienced treatment failure. Treatment failure almost always occurred within
      the first year of spinal instrumentation. 

PMID- 24277040
TI  - Antifungal application of nonantifungal drugs.
AB  - Candida species are the cause of 60% of all mycoses in immunosuppressed
      individuals, leading to ~150,000 deaths annually due to systemic infections,
      whereas the current antifungal therapies either have toxic side effects or are
      insufficiently efficient. We performed a screening of two compound libraries, the
      Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection
      library, for anti-Candida activity based on the European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844
      drugs, 26 agents showed activity against Candida albicans. Of those, 12 were
      standard antifungal drugs (SADs) and 7 were off-target drugs previously reported
      to be active against Candida spp. The remaining 7 off-target drugs, amonafide,
      tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol,
      and haloperidol, were identified with this screen. The anti-Candida activities of
      the new agents were investigated by three individual assays using optical
      density, ATP levels, and microscopy. The antifungal activities of these drugs
      were comparable to those of the SADs found in the screen. The aminopeptidase
      inhibitor tosedostat, which is currently in a clinical trial phase for anticancer
      therapy, displayed a broad antifungal activity against different Candida spp.,
      including Candida glabrata. Thus, this screen reveals agents that were previously
      unknown to be anti-Candida agents, which allows for the design of novel therapies
      against invasive candidiasis. 

PMID- 24277041
TI  - Metronidazole and hydroxymetronidazole central nervous system distribution: 1.
      microdialysis assessment of brain extracellular fluid concentrations in patients
      with acute brain injury.
AB  - The distribution of metronidazole in the central nervous system has only been
      described based on cerebrospinal fluid data. However, extracellular fluid (ECF)
      concentrations may better predict its antimicrobial effect and/or side effects.
      We sought to explore by microdialysis brain ECF metronidazole distribution in
      patients with acute brain injury. Four brain-injured patients monitored by
      cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h.
      Brain dialysates and blood samples were collected at steady state over 8 h. Probe
      recoveries were evaluated by in vivo retrodialysis in each patient for
      metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure
      liquid chromatography, and a noncompartmental pharmacokinetic analysis was
      performed. Probe recovery was equal to 78.8% +/- 1.3% for metronidazole in
      patients. Unbound brain metronidazole concentration-time curves were delayed
      compared to unbound plasma concentration-time curves but with a mean
      metronidazole unbound brain/plasma AUC0-tau ratio equal to 102% +/- 19% (ranging
      from 87 to 124%). The unbound plasma concentration-time profiles for OH
      metronidazole were flat, with mean average steady-state concentrations equal to
      4.0 +/- 0.7 MUg ml(-1). This microdialysis study describes the steady-state brain
      distribution of metronidazole in patients and confirms its extensive
      distribution. 

PMID- 24277042
TI  - Novel method to identify the optimal antimicrobial peptide in a combination
      matrix, using anoplin as an example.
AB  - Microbial resistance is an increasing health concern and a true danger to human
      well-being. A worldwide search for new compounds is ongoing, and antimicrobial
      peptides are promising lead candidates for tomorrow's antibiotics. The
      decapeptide anoplin (GLLKRIKTLL-NH2) is an especially interesting candidate
      because of its small size as well as its antimicrobial and nonhemolytic
      properties. Optimization of the properties of an antimicrobial peptide such as
      anoplin requires multidimensional searching in a complex chemical space.
      Typically, such optimization is performed by labor-intensive and costly trial-and
      error methods. In this study, we show the benefit of fractional factorial design
      for identification of the optimal antimicrobial peptide in a combination matrix.
      We synthesized and analyzed a training set of 12 anoplin analogs, representative
      of 64 analogs in total. Using MIC, hemolysis, and high-performance liquid
      chromatography retention time data, we constructed analysis-of-variance models
      that describe the relationship between these properties and the structural
      characteristics of the analogs. We show that the mathematical models derived from
      the training set data can be used to predict the properties of other analogs in
      the chemical space. Hence, this method provides an efficient means of
      identification of the optimal peptide in the searched chemical space. 

PMID- 24277043
TI  - Identification of 50 class D beta-lactamases and 65 Acinetobacter-derived
      cephalosporinases in Acinetobacter spp.
AB  - Whole-genome sequencing of a collection of 103 Acinetobacter strains belonging to
      22 validly named species and another 16 putative species allowed detection of
      genes for 50 new class D beta-lactamases and 65 new Acinetobacter-derived
      cephalosporinases (ADC). All oxacillinases (OXA) contained the three typical
      motifs of class D beta-lactamases, STFK, (F/Y)GN, and K(S/T)G. The phylogenetic
      tree drawn from the OXA sequences led to an increase in the number of OXA groups
      from 7 to 18. The topologies of the OXA and RpoB phylogenetic trees were similar,
      supporting the ancient acquisition of blaOXA genes by Acinetobacter species. The
      class D beta-lactamase genes appeared to be intrinsic to several species, such as
      Acinetobacter baumannii, Acinetobacter pittii, Acinetobacter calcoaceticus, and
      Acinetobacter lwoffii. Neither blaOXA-40/143- nor blaOXA-58-like genes were
      detected, and their origin remains therefore unknown. The phylogenetic tree
      analysis based on the alignment of the sequences deduced from blaADC revealed
      five main clusters, one containing ADC belonging to species closely related to A.
      baumannii and the others composed of cephalosporinases from the remaining
      species. No indication of blaOXA or blaADC transfer was observed between
      distantly related species, except for blaOXA-279, possibly transferred from
      Acinetobacter genomic species 6 to Acinetobacter parvus. Analysis of beta-lactam
      susceptibility of seven strains harboring new oxacillinases and cloning of the
      corresponding genes in Escherichia coli and in a susceptible A. baumannii strain
      indicated very weak hydrolysis of carbapenems. Overall, this study reveals a
      large pool of beta-lactamases in different Acinetobacter spp., potentially
      transferable to pathogenic strains of the genus. 

PMID- 24277044
TI  - Role of the mecA gene in oxacillin resistance in a Staphylococcus aureus clinical
      strain with a pvl-positive ST59 genetic background.
AB  - The most prevalent community-associated methicillin-resistant Staphylococcus
      aureus (C-MRSA) strains in Taiwan, sequence type 59 (ST59) clones, carry
      staphylococcal cassette chromosome mec (SCCmec) type V and, to a lesser extent,
      type IV. These strains show wide variation in sensitivity to oxacillin, but the
      reasons for this variation are unknown. Here we compared the sequences of the
      mecA genes from clinical strains of different SCCmec types and found that they
      contain different mecA promoter mutations. Analysis of mecA promoter activity by
      reporter gene fusions showed that single base substitutions in the promoter have
      a strong influence on mecA transcription. The different mecA variants, including
      promoter sequences, were expressed in the methicillin-sensitive Staphylococcus
      aureus (MSSA) strain C195 (ST59 background). PBP 2a production among the parental
      strains and strains with promoter mutant mecA genes showed a close correlation
      with mecA transcription levels. Furthermore, the quantity of PBP 2a also closely
      correlated with the level of oxacillin resistance in the C195 background. Our
      data suggest that mecA promoter mutations play an important role in determining
      the level of oxacillin resistance. The mecA promoter mutation G-25A (25 bases
      upstream of the mecA translation start site) was found to be associated with a
      high oxacillin MIC (256 MUg/ml), G-7T conferred a moderate oxacillin MIC (32 to
      64 MUg/ml), strains with C-33T showed a low oxacillin MIC (4 to 8 MUg/ml), and A
      38G reversed the effect of the C-33T mutation, restoring the oxacillin resistance
      level in the A-38G C-33T double mutant. These observations may explain why C-MRSA
      strains in Taiwan carrying SCCmec type IV or V have such enormous variations in
      oxacillin MICs. 

PMID- 24277045
TI  - A novel staphylococcal cassette chromosomal element, SCCfusC, carrying fusC and
      speG in fusidic acid-resistant methicillin-resistant Staphylococcus aureus.
AB  - A high prevalence of fusC (16/46, 59%) was found in fusidic acid-resistant
      methicillin-resistant Staphylococcus aureus isolates collected from 2008 to 2010.
      Nucleotide sequencing of fusC and flanking regions revealed a novel
      staphylococcal cassette chromosome (SCC) structure, SCCfusC, which was integrated
      into rlmH and located upstream from SCCmec. The SCCfusC element contained speG,
      which may contribute to the polyamine resistance. 

PMID- 24277046
TI  - Severe sepsis facilitates intestinal colonization by extended-spectrum-beta
      lactamase-producing Klebsiella pneumoniae and transfer of the SHV-18 resistance
      gene to Escherichia coli during antimicrobial treatment.
AB  - Infections caused by multidrug-resistant pathogens are frequent and life
      threatening in critically ill patients. To investigate whether severe sepsis
      affects gut colonization by resistant pathogens and genetic exchange between
      opportunistic pathogens, we tested the intestinal-colonization ability of an
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain carrying
      the SHV-18 resistance gene and the transfer ability of the resistance gene to
      endogenous Escherichia coli under ceftriaxone treatment in rats with burn injury
      only or severe sepsis induced by burns plus endotoxin exposure. Without
      ceftriaxone treatment, the K. pneumoniae strain colonized the intestine in both
      septic and burned rats for a short time, with clearance occurring earlier in burn
      only rats but never in sham burn rats. In both burned and septic rats, the
      colonization level of the challenge strain dropped at the beginning and then
      later increased during ceftriaxone treatment, after which it declined gradually.
      This pattern coincided with the change in resistance of K. pneumoniae to
      ceftriaxone during and after ceftriaxone treatment. Compared with burn-only
      injury, severe sepsis had a more significant effect on the change in
      antimicrobial resistance to ceftriaxone. Only in septic rats was the resistance
      gene successfully transferred from the challenge strain to endogenous E. coli
      during ceftriaxone treatment; the gene persisted for at least 4 weeks after
      ceftriaxone treatment. We concluded that severe sepsis can facilitate intestinal
      colonization by an exogenous resistant pathogen and the transfer of the
      resistance gene to a potential endogenous pathogen during antimicrobial
      treatment. 

PMID- 24277047
TI  - More complications occur in macrolide-resistant than in macrolide-sensitive
      Mycoplasma pneumoniae pneumonia.
AB  - We sought to understand the situation of macrolide-resistant genotypes of
      Mycoplasma pneumoniae, and analyze the relationship between macrolide-resistant
      genotypes and clinical manifestations of Mycoplasma pneumoniae pneumonia (MPP).
      Full-length sequencing of the 23S rRNA gene of M. pneumoniae was performed in 235
      nasopharyngeal aspirates (NPAs) from children with MPP. We also retrospectively
      compared the clinical characteristics of macrolide-resistant (MR) M. pneumoniae
      infections and macrolide-sensitive (MS) M. pneumoniae infections. A total of 206
      patients had point mutations in the M. pneumoniae 23S rRNA gene, and these
      patients are referred to as MR patients. The remaining 29 patients without point
      mutations are referred to as MS patients. Among 206 MR patients, 199 (96.6%) had
      A2063G mutations, 6 had A2063T mutations, and the remaining patients had an
      A2064G mutation. Among the clinical manifestations, we found that the median
      fever durations were 8 days (range, 0 to 42 days) and 6 days (0 to 14 days) (P <
      0.01), the median hospitalization durations were 8 days (2 to 45 days) and 6 days
      (3 to 16 days) (P < 0.01), and the median fever durations after macrolide therapy
      were 5 days (0 to 42 days) and 3 days (0 to 10 days) (P < 0.01), respectively, in
      the MR and MS groups. We also found that the incidence of extrapulmonary
      complications in the MR group was significantly higher than that in the MS group
      (P < 0.05). Moreover, the radiological findings were more serious in the MR group
      than in the MS group (P < 0.05). The increasing prevalence of MR M. pneumoniae
      has become a significant clinical issue in the pediatric patients, which may lead
      to more extrapulmonary complications and severe clinical features and
      radiological manifestations. 

PMID- 24277049
TI  - Fecal carriage of methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococcus in healthy children.

PMID- 24277048
TI  - The Burkholderia pseudomallei enoyl-acyl carrier protein reductase FabI1 is
      essential for in vivo growth and is the target of a novel chemotherapeutic with
      efficacy.
AB  - The bacterial fatty acid biosynthesis pathway is a validated target for the
      development of novel chemotherapeutics. However, since Burkholderia pseudomallei
      carries genes that encode both FabI and FabV enoyl-acyl carrier protein (ACP)
      reductase homologues, the enoyl-ACP reductase that is essential for in vivo
      growth needs to be defined so that the correct drug target can be chosen for
      development. Accordingly, DeltafabI1, DeltafabI2, and DeltafabV knockout strains
      were constructed and tested in a mouse model of infection. Mice infected with a
      DeltafabI1 strain did not show signs of morbidity, mortality, or dissemination
      after 30 days of infection compared to the wild-type and DeltafabI2 and DeltafabV
      mutant strains that had times to mortality of 60 to 84 h. Although signs of
      morbidity and mortality of DeltafabI2 and DeltafabV strains were not
      significantly different from those of the wild-type strain, a slight delay was
      observed. A FabI1-specific inhibitor was used to confirm that inhibition of FabI1
      results in reduced bacterial burden and efficacy in an acute B. pseudomallei
      murine model of infection. This work establishes that FabI1 is required for
      growth of Burkholderia pseudomallei in vivo and is a potential molecular target
      for drug development. 

PMID- 24277050
TI  - Metronidazole and hydroxymetronidazole central nervous system distribution: 2.
      cerebrospinal fluid concentration measurements in patients with external
      ventricular drain.
AB  - This study explored metronidazole and hydroxymetronidazole distribution in the
      cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients
      with external ventricular drain received 500 mg of metronidazole over 0.5 h every
      8 h. CSF and blood samples were collected at steady state over 8 h, and the
      metronidazole and hydroxymetronidazole concentrations were assayed by high
      pressure liquid chromatograph. A noncompartmental analysis was performed.
      Metronidazole is distributed extensively within CSF, with a mean CSF to unbound
      plasma AUC0-tau ratio of 86% +/- 16%. However, the concentration profiles in CSF
      were mostly flat compared to the plasma profiles. Hydroxymetronidazole
      concentrations were much lower than those of metronidazole both in plasma and in
      CSF, with a corresponding CSF/unbound plasma AUC0-tau ratio of 79% +/- 16%. We
      describe here for the first time in detail the pharmacokinetics of metronidazole
      and hydroxymetronidazole in CSF. 

PMID- 24277051
TI  - Detection of Enteroviruses in Influent and Effluent Flow Samples from Wastewater
      Treatment Plants in Italy.
AB  - This study evaluated the presence and seasonal distribution of polio and other
      enteroviruses in four wastewater treatment plants in three cities in Italy, using
      different treatment systems. Detection of enteroviruses was carried out by virus
      isolation in cell cultures after concentration of water samples collected at both
      inlet and outlet of the treatment plants, following the methods described in the
      WHO guidelines. Viral serotypes isolated before and after water treatment were
      compared. Forty-eight non-polio enteroviruses were isolated from 312 samples
      collected at the inlet of the four wastewater treatment plants, 35 of which were
      Coxsackievirus type B (72.9 %) and 13 Echovirus (27.1 %). After treatment, 2
      CVB3, 1 CVB5, and 1 Echo 6 were isolated. CVB3 and Echo 6 serotypes were also
      detected in samples collected at the inlet of the TP, in the same month and year.
      The high rate of detection of infectious enteroviruses in inlet sewage samples
      (30.1 %) indicates wide diffusion of these viruses in the populations linked to
      the collectors. The incomplete removal of infectious viruses following sewage
      treatment highlights possible risks for public health relate to treated waters
      discharge into the environment. 

PMID- 24277053
TI  - Colorectal cancer prognosis and PPARdelta/beta expression in the tumor
      microenvironment.

PMID- 24277052
TI  - Type 2 diabetes mellitus is associated with the fibrosis severity in patients
      with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese
      patients.
AB  - BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) and
      metabolic syndrome have been increasing worldwide. The associations between
      metabolic factors and the histologic severity of NAFLD have not yet been
      clarified. Therefore, we studied the relationships between relevant metabolic
      factors and the histological severity of NAFLD. METHODS: In a cross-sectional
      multicenter study conducted in Japan, we examined 1,365 biopsy-proven NAFLD
      patients. The frequencies of underlying lifestyle-related diseases and their
      relationships to the NAFLD histology were investigated. RESULTS: The hepatic
      fibrosis stages (Stage 0/1/2/3/4) were 22.6/34.1/26.7/14.5/2.1 (%) in the male
      patients, and 16.2/31.7/23.9/21.6/6.6 (%) in the female patients. Dyslipidemia
      was present in 65.7% (hypertriglyceridemia, 45.3%; increased low-density
      lipoprotein cholesterol, 37.5%; decreased high density lipoprotein cholesterol,
      19.5%) of patients. Hypertension was present in 30.2%, and diabetes mellitus (DM)
      in 47.3%. The fibrosis stage increased with age, especially in postmenopausal
      females. The body mass index was positively correlated with the fibrosis stage.
      Deterioration of glucose control was positively correlated with the fibrosis
      stage, this correlation being more prominent in females. Multivariate analysis
      identified age and DM as significant risk factors for advanced fibrosis. No
      significant correlation of the fibrosis stage was observed with hypertension.
      There was a negative correlation between the serum triglyceride levels and the
      fibrosis stage. CONCLUSIONS: DM appeared to be a significant risk factor for
      advanced fibrosis in patients with NAFLD, and would therefore need to be properly
      managed to prevent the progression of NAFLD.

PMID- 24277054
TI  - New ACC/AHA prevention guidelines: building a bridge to even stronger guideline
      collaborations.

PMID- 24277055
TI  - Effect of remote ischemic preconditioning on platelet activation and reactivity
      induced by ablation for atrial fibrillation.
AB  - BACKGROUND: Radiofrequency ablation of atrial fibrillation has been associated
      with some risk of thromboembolic events. Previous studies showed that preventive
      short episodes of forearm ischemia (remote ischemic preconditioning [IPC]) reduce
      exercise-induced platelet reactivity. In this study, we assessed whether remote
      IPC has any effect on platelet activation induced by radiofrequency ablation of
      atrial fibrillation. METHODS AND RESULTS: We randomized 19 patients (age, 54.7+/
      11 years; 17 male) undergoing radiofrequency catheter ablation of paroxysmal
      atrial fibrillation to receive remote IPC or sham intermittent forearm ischemia
      (control subjects) before the procedure. Blood venous samples were collected
      before and after remote IPC/sham ischemia, at the end of the ablation procedure,
      and 24 hours later. Platelet activation and reactivity were assessed by flow
      cytometry by measuring monocyte-platelet aggregate formation, platelet CD41 in
      the monocyte-platelet aggregate gate, and platelet CD41 and CD62 in the platelet
      gate in the absence and presence of ADP stimulation. At baseline, there were no
      differences between groups in platelet variables. Radiofrequency ablation induced
      platelet activation in both groups, which persisted after 24 hours. However,
      compared with control subjects, remote IPC patients showed a lower increase in
      all platelet variables, including monocyte-platelet aggregate formation
      (P<0.0001), CD41 in the monocyte-platelet aggregate gate (P=0.002), and CD41
      (P<0.0001) and CD62 (P=0.002) in the platelet gate. Compared with control
      subjects, remote IPC was also associated with a significantly lower ADP-induced
      increase in all platelet markers. CONCLUSIONS: Our data show that remote IPC
      before radiofrequency catheter ablation for paroxysmal atrial fibrillation
      significantly reduces the increased platelet activation and reactivity associated
      with the procedure.

PMID- 24277056
TI  - Platelet activation after radiofrequency ablation in atrial fibrillation: is
      there any clinical implication?

PMID- 24277057
TI  - The world in tune.

PMID- 24277058
TI  - Religion and medicine: How are they related?
AB  - This paper provides a comprehensive and dynamic profile of religion-medicine
      interrelationships. This profile is drawn from the respective characteristics of
      religion and medicine, as well as from historic and contemporary literature
      regarding their interconnections. Six symbiotic functions are identified and
      discussed with respect to their bearing on clinical practice, medical education,
      and research. 

PMID- 24277059
TI  - "Reflections on a peach-seed monkey": Empowering relationships.
AB  - The focus of this essay is on human relationships, specifically, the empowering
      potential of those relationships, and, most particularly, on the empowering
      potential those relationships have for enabling us to discover our respective
      possibilities. It is argued that we often discover who we are and what we can
      become as our possibilities are discovered by another and reflected back to us.
      This empowering potential of human relationships can be helpfully understood as a
      manifestation of the redemptive role of God in human life. 

PMID- 24277060
TI  - Family stress theory: A perspective on pastoral care.
AB  - This article reviews crisis theory from family stress literature and research
      from medical sociology to advance a rationale for clinical pastoral care of
      seriously ill patients and families. It describes Reuben Hill's A,B,C,X crisis
      model and offers it as a conceptual framework for understanding the psychosocial
      experiences of families facing illness and the role of pastoral care in the
      coping process. 

PMID- 24277061
TI  - Perceived life quality of older and younger tibetans.
AB  - Tibetans have enjoyed a reputation for contentment and a jovial disposition. This
      study examines the extent to which this positive outlook on life persists despite
      their 25-year stay as refugees in India, and the transferability of this positive
      outlook to first-generation, Indian-born Tibetans. With this in mind, older
      Tibetan refugees (N = 45) and younger Tibetan refugees (N = 45) residing in
      Himachal Pradesh in India were administered the Life Quality Scale (Q.O.L.). As
      expected, younger Tibetan refugees shared significant characteristics on the
      Q.O.L. scale with older Tibetans. Similarities and differences in the outlook of
      the two age groups are examined. 

PMID- 24277062
TI  - Anxiety.
AB  - The analysis is a study of the nature of anxiety in human experience. The author
      reviews the work of theologian Paul Tillich and psychologist Rollo May and
      clarifies the role of anxiety in life. The article reflects the need for a basic
      religious affirmation as one faces the anxiety of life which comes from the many
      threats to human existence. 

PMID- 24277063
TI  - Religiosity and psychological distress among blacks.
AB  - The influence of religion on mental well-being has been the subject of
      controversy for a long while. Yet little is known about this relationship among
      black Americans. Using a probability-based sample of 451 urban black Americans,
      this study examines gender differences in religiosity and explores the
      ramifications for mental health. Findings indicate that females are more
      religious than males as evidenced by their greater participation in
      organizational forms of religious practice such as meetings and other gatherings.
      However, for both males and females, religiosity varied significantly by age and
      by marital and parental status. On the other hand, there were no differences in
      religiosity according to levels of education, income, and employment status for
      either males or females. With regard to mental health, greater religiosity was
      associated with fewer depressive symptoms for both males and females. Further, in
      the event of stressful circumstances, the influence of religion on mental well
      being for females was direct, while religious involvement appeared to have an
      indirect or stress- buffering effect for males. 

PMID- 24277064
TI  - Control of Ehrlich cell division by zinc.
AB  - The nutritional requirement for zinc in the proliferation of normal and malignant
      cells has been demonstrated in a number of animal studies. A distinction is made
      between the effect of zinc status upon the host during carcinogenesis and tumor
      growth. The present studies focus on the Ehrlich ascites tumor in mice fed a
      semipurified zinc-deficient diet along with defined concentration of zinc in the
      drinking water. This model of zinc deficiency is compared with others in which
      chelating agents are used to create zinc-deficient conditions or the
      microorganismEuglena gracilis is examined in a defined zinc-deficient medium. It
      is reported here that Ehrlich cells remain quiescent for several weeks in
      severely deficient mice, suggesting their restriction to a G1 or G0 state of the
      cell cycle. The kinetics of thymidine and uridine uptake and incorporation into
      DNA and RNA in Zn-normal and Zn-deficient tumors is consistent with the
      inhibition of thymidine kinase and DNA polymerase in the Zn-deprived system, but
      with little effect on RNA synthesis. The concentration of metabolites of these
      labeled nucleosides in Ehrlich cells is also consistent with a primary effect
      upon thymidine kinase. Although the ascites fluid Zn is depressed in Zn
      deficiency, total cellular zinc and its distribution among cell fractions is not
      significantly affected. It is suggested that these effects are specific in nature
      and not the result of a general lack of zinc for zinc metalloproteins and other
      binding sites in the cell. 

PMID- 24277065
TI  - The intracellular metabolism of iodine in carcinogenesis.
AB  - Research from this laboratory and others have concluded that significant
      glandular atypia, and often neoplasia, occurs in the breast tissues of rodents
      and humans under conditions of iodine deprivation. These cellular changes caused
      by iodine deficiency are intensified, by aging, steroid hormones, and pituitary
      hormones. There has been controversy concerning the effect of iodine deficiency
      on stimulation and maintenance of cancer of the breast in rodents when the cancer
      is induced chemically or by transplantation. However, neither within this induced
      neoplastic framework nor with the dysplastic changes seen by deficiency alone
      have laboratory studies of thepathway of intracellular iodine been previously
      possible.The new research data addresses the question of whether organification
      occurs and whether iodine significantly affects the intracellular structures. An
      hypothesis will be presented that places the inorganic element, iodine, into
      association with receptor protein complexes that may be responsible for
      intracellular sex hormone activity. The relationship of this mechanism to
      carcinogenesis in breast tissue will be considered. 

PMID- 24277066
TI  - Dietary practices, site-specific tumors, and age-at-death relationships.
AB  - When rats are given freedom of dietary choice, the quantity and composition of
      the diet selected varies from animal to animal, but the risk to the individual of
      developing a variety of neoplasms is greatly increased over that of rats fed
      fixed diets. The increase in frequency of tumors cannot be explained on the basis
      of the amount or the composition of the diet selected. However, the application
      of "variable selection" statistical procedures shows that there are combinations
      of temporal-specific interacting dietary and dietary-dependent variables that are
      closely linked with cancer mortality. The multi-variable statistical model for
      animals dying with one type of tumor is not applicable to those dying with tumors
      of other types or sites. In every case, the only data required to characterize
      the dates of death of tumor-bearing individuals are those describing the dietary
      practices and growth responses prior to maturity. The model for animals with
      pancreatic tumors is used to illustrate the extent to which dietary practices of
      early life are linked with the animals' survival. 

PMID- 24277067
TI  - Role in hemolysis of the interaction of tellurium compounds with glutathione :
      Comparison with the hemolysis produced by mercury compounds.
AB  - We have shown that tellurite and tellurate require the interaction with reduced
      glutathione (GSH) to hemolyze human erythrocytes. The study of the nature of this
      interaction is the main object of this paper. The degree of hemolysis was
      determined by the method of Angelone. The addition of extracellular 1 mM GSH or
      cysteine increased the rate of hemolysis. Concanavalin A (0.3 mg/mL) and/or 4
      mg/mL adenosine did not affect the hemolysis by 0.1 mM tellurite. One tenth to 1
      mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) inhibited this
      hemolysis by 60-100%. Millimolar GSH released this inhibition. Incubation of 0.1
      mM tellurite with 1 mM GSH for 90 min at 37 degrees C, produced a hemolytic agent
      when prepared and tested under nitrogen, but one that was not active when
      prepared in air. The hemolysis byp-hydroxymercuribenzoate orp
      hydroxymercuriphenylsulfonate did not involve GSH. Scanning electron micrographs
      showed a sphero-echinocyte transformation, in the pre-hemolytic stage, with all
      the agents tested. The rate of penetration of tellurite plays a role in
      determining the rate of hemolysis, as shown by the effect of SITS. The release by
      GSH of the inhibition by SITS poses questions concerning the site of action and
      cell membrane penetration of the hemolytic agent. Telluride or some intermediate
      in the interaction of GSH with tellurite is the actual hemolytic agent. 

PMID- 24277068
TI  - A survey of the effect of metals on the immune response.
AB  - CONCLUSIONS: Evidence has been presented that the effect of metals on the immune
      response is highly variable: either enhancement or suppression may occur,
      depending on metal dose, route of inoculation, nature of antigenic stimulus, time
      of metal administration in relation to antigen, or the specific class of
      immunoglobulins produced. Very little is known of the mechanisms of metal-induced
      suppression or enhancement; mitogenicity of some metals may be involved in their
      stimulatory effects on immunity.An evaluation of available data shown no
      significant difference in the effect of carcinogenic and noncarcinogenic metals
      on immunity; the general effect of carcinogenic metals appears to be that of
      immunosuppression, but enhancement of immunity may also occur.Additional studies
      are needed to define immunological effects of carcinogenic and noncarcinogenic
      metals. Few experiments have analyzed the effects of these metals on cellular
      aspects of immunity, and, especially on those immunological reactions that play a
      role in tumor suppression or enhancement.

PMID- 24277069
TI  - Binding of(51)Cr to human erythrocytes.
AB  - Radioactive chromium accumulated in human erythrocytes exists in two forms: one
      bound to macromolecules, e.g., hemoglobin, and one in a low molecular weight
      form. Both forms are released from cells either spontaneously or as a result of
      toxic induction. 

PMID- 24277070
TI  - Coordinated regulation by iron of the synthesis of two transformation-sensitive
      membrane proteins in NRK cells.
AB  - Studies were designed to characterize the plasma membrane polypeptide composition
      of normal rat kidney (NRK) and virus-transformed NRK cells as a function of time
      following iron deprivation. Using this approach we found that rapid depletion of
      iron from the cells increases the amounts of two membrane-associated
      glycoproteins of apparent MW 160,000 (160 K) and 130,000 (130 K) in NRK cells. In
      contrast, virus-transformed NRK cells subjected to iron deprivation showed an
      altered induction phenomenon manifested by reduced levels of both 160 K and 130 K
      and altered time-sequence of the induction. Possible relationship of the 160 K
      and 130 K membrane-associated glycoproteins described in this study to growth
      control and viral transformation are discussed. 

PMID- 24277071
TI  - Unusual metals as carcinogens.
AB  - A review of the literature on unusual metals as carcinogens was carried out. The
      metals covered are some of the rare earths, copper, silver, gold, mercury,
      germanium, tin, antimony, lead, platinum, palladium, aluminum, titanium, niobium,
      manganese, scandium, yttrium, indium, rhodium, and gallium. 

PMID- 24277072
TI  - Re: The relationship between head injury and facial trauma.

PMID- 24277073
TI  - UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances
      long-term outcomes in Philadelphia positive acute lymphoblastic leukemia.
AB  - The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult
      acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003
      (pre-imatinib cohort). In 2003 imatinib was introduced as a single-agent course
      following induction (N = 86, late imatinib). In 2005 imatinib was added to the
      second phase of induction (N = 89, early imatinib). The complete remission (CR)
      rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004).
      At 4 years, the overall survival (OS) of all patients in the imatinib cohort was
      38% vs 22% in the preimatinib cohort (P = .003). The magnitude of the difference
      between the preimatinib and imatinib cohorts in event-free survival (EFS), OS,
      and relapse-free survival (RFS) seen in univariate analysis was even greater in
      the multivariate analysis. In the preimatinib cohort, 31% of those starting
      treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with
      46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into
      account showed a modest additional benefit to imatinib (hazard ratio for EFS =
      0.64, 95% confidence interval 0.44-0.93, P = .02), but no significant benefit for
      OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS
      for adults with ALL. A proportion of the OS benefit derives from the fact that
      imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as
      NCT00002514. 

PMID- 24277074
TI  - Cooperative transcriptional repression by BCL6 and BACH2 in germinal center B
      cell differentiation.
AB  - The transcriptional repressors BCL6 and BACH2 are crucial regulators of germinal
      center (GC) B-cell fate, and are known to interact and repress transcription of
      PRDM1, a key driver of plasma cell differentiation. How these factors cooperate
      is not fully understood. Herein, we show that GC formation is only minimally
      impaired in Bcl6(+/-) or Bach2(+/-) mice, although double heterozygous Bcl6(+/
      )Bach2(+/-) mice exhibit profound reduction in GC formation. Splenic B cells from
      Bcl6(+/-) Bach2(+/-) mice display accelerated plasmacytic differentiation and
      high expression of key plasma cell genes such as Prdm1, Xbp1, and CD138.
      Chromatin immunoprecipitation sequencing revealed that in B cells, BACH2 is
      mostly bound to genes together with its heterodimer partner MAFK. The BACH2-MAFK
      complex binds to sets of genes known to be involved in the GC response, 60% of
      which are also targets of BCL6. Approximately 30% of BACH2 peaks overlap with
      BCL6, including cis-regulatory sequences of the PRDM1 gene. BCL6 also modulates
      BACH2 protein stability and their protein levels are positively correlated in GC
      B cells. Therefore, BCL6 and BACH2 cooperate to orchestrate gene expression
      patterning in GC B cells through both transcriptional and biochemical mechanisms,
      which collectively determine the proper initiation and timing of terminal
      differentiation. 

PMID- 24277075
TI  - CXCR7 participates in CXCL12-induced CD34+ cell cycling through beta-arrestin
      dependent Akt activation.
AB  - In addition to its well-known effect on migration and homing of hematopoietic
      stem/progenitor cells (HSPCs), CXCL12 chemokine also exhibits a cell cycle and
      survival-promoting factor for human CD34(+) HSPCs. CXCR4 was suggested to be
      responsible for CXCL12-induced biological effects until the recent discovery of
      its second receptor, CXCR7. Until now, the participation of CXCR7 in CXCL12
      induced HSPC cycling and survival is unknown. We show here that CXCL12 was
      capable of binding CXCR7 despite its scarce expression at CD34(+) cell surface.
      Blocking CXCR7 inhibited CXCL12-induced Akt activation as well as the percentage
      of CD34(+) cells in cycle, colony formation, and survival, demonstrating its
      participation in CXCL12-induced functional effects in HSPCs. At steady state,
      CXCR7 and beta-arrestin2 co-localized near the plasma membrane of CD34(+) cells.
      After CXCL12 treatment, beta-arrestin2 translocated to the nucleus, and this
      required both CXCR7 and CXCR4. Silencing beta-arrestin expression decreased
      CXCL12-induced Akt activation in CD34(+) cells. Our results demonstrate for the
      first time the role of CXCR7, complementary to that played by CXCR4, in the
      control of HSPC cycling, survival, and colony formation induced by CXCL12. We
      also provide evidence for the involvement of beta-arrestins as signaling hubs
      downstream of both CXCL12 receptors in primary human HSPCs. 

PMID- 24277076
TI  - The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic
      lymphocytic leukemia cell motility and causes chemosensitization.
AB  - The CXC chemokine ligand (CXCL12, or stromal cell-derived factor-1 as previously
      known) plays a critical role for homing and retention of chronic lymphocytic
      leukemia (CLL) cells in tissues such as the bone marrow (BM). In tissues, stromal
      cells constitutively secrete and present CXCL12 via cell-surface-bound
      glycosaminoglycans (GAGs), thereby attracting CLL cells and protecting them from
      cytotoxic drugs, a mechanism that may account for residual disease after
      conventional CLL therapy. NOX-A12, an RNA oligonucleotide in L-configuration
      (Spiegelmer) that binds and neutralizes CXCL12, was developed for interference
      with CXCL12 in the tumor microenvironment and for cell mobilization. Here, we
      examined effects of NOX-A12 on CLL cell migration and drug sensitivity. We found
      that NOX-A12 effectively inhibited CXCL12-induced chemotaxis of CLL cells. In
      contrast, NOX-A12 increased CLL migration underneath a confluent layer of BM
      stromal cells (BMSCs) due to interference with the CXCL12 gradient established by
      BMSCs. In particular, NOX-A12 competes with GAGs such as heparin for CXCL12
      binding, leading to the release of CXCL12 from stromal cell-surface-bound GAGs,
      and thereby to neutralization of the chemokine. Furthermore, NOX-A12 sensitizes
      CLL cells toward bendamustine and fludarabine in BMSC cocultures. These data
      demonstrate that NOX-A12 effectively interferes with CLL cell migration and BMSC
      mediated drug resistance, and establishes a rationale for clinical development of
      NOX-A12 in combination with conventional agents in CLL. 

PMID- 24277077
TI  - Aggf1 acts at the top of the genetic regulatory hierarchy in specification of
      hemangioblasts in zebrafish.
AB  - The hemangioblast is a multipotential progenitor, which is derived from the
      mesoderm and can further differentiate into hematopoietic and endothelial
      lineages. The molecular mechanism governing the specification of hemangioblasts
      is fundamental to regenerative medicine based on embryonic stem cells for the
      treatment of various hematologic and vascular diseases. Here we show that aggf1
      acts at the top of the genetic regulatory hierarchy in the specification of
      hemangioblasts in zebrafish. Knockdown of aggf1 expression decreases expression
      of endothelial cell-specific markers (cdh5, admr) and disrupts primitive
      hematopoiesis as shown by a decreased number of erythroid cells and reduced
      expression of gata1 (marker for erythroid progenitors) and pu.1 (myeloid
      progenitors). Aggf1 knockdown also decreases expression of runx1 and c-myb,
      indicating that it is required for specification of hematopoietic stem cells
      (definitive hematopoiesis). Aggf1 knockdown led to dramatically reduced
      expression of hemangioblast markers fli1, etsrp, lmo2, and scl, and
      hematopoietic/endothelial defects in aggf1 morphants were rescued by messenger
      RNA for scl, fli-vp16, or etsrp. Taken together, these data indicate that aggf1
      is involved in differentiation of both hematopoietic and endothelial lineages and
      that aggf1 acts upstream of scl, fli1, and etsrp in specification of
      hemangioblasts. 

PMID- 24277078
TI  - Inhibition of thrombotic properties of persistent autoimmune anti-beta2GPI
      antibodies in the mouse model of antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder with increased risk for
      thrombosis and pregnancy losses. beta2-glycoprotein I (beta2GPI) is the major
      antigen for clinically relevant antibodies in APS. We engineered a molecule, A1
      A1, which interferes with 2 prothrombotic mechanisms in APS: the binding of
      beta2GPI to negatively charged cellular surfaces and ApoE receptor 2. We studied
      how A1-A1 affects arterial thrombosis in vivo in lupus-prone (NZW * BXSB)F1 male
      mice. For the first time, we demonstrated that A1-A1 efficiently reduces thrombus
      size in vivo in the presence of chronic autoimmune anti-beta2GPI antibodies. We
      have shown that A1-A1 interferes with thrombotic properties of beta2GPI/antibody
      complexes and does not affect normal thrombus formation in the absence of anti
      beta2GPI antibodies. A1-A1 inhibits prothrombotic properties of beta2GPI/antibody
      complexes in wild-type mice after acute infusion with anti-beta2GPI antibodies,
      as well as in mice expressing persistent autoimmune anti-beta2GPI antibodies. A1
      A1 reduced thrombus size in a mouse model of APS in the presence of lupus
      features, suggesting that A1-A1 might effectively interfere with thrombosis not
      only in primary APS but also in APS secondary to lupus. Our results suggest that
      A1-A1 could be a prototype for an antithrombotic drug in APS. 

PMID- 24277079
TI  - Heme triggers TLR4 signaling leading to endothelial cell activation and vaso
      occlusion in murine sickle cell disease.
AB  - Treatment of sickle cell disease (SCD) is hampered by incomplete understanding of
      pathways linking hemolysis to vaso-occlusion. We investigated these pathways in
      transgenic sickle mice. Infusion of hemoglobin or heme triggered vaso-occlusion
      in sickle, but not normal, mice. Methemoglobin, but not heme-stabilized
      cyanomethemoglobin, induced vaso-occlusion, indicating heme liberation is
      necessary. In corroboration, hemoglobin-induced vaso-occlusion was blocked by the
      methemoglobin reducing agent methylene blue, haptoglobin, or the heme-binding
      protein hemopexin. Untreated HbSS mice, but not HbAA mice, exhibited ~10% vaso
      occlusion in steady state that was inhibited by haptoglobin or hemopexin
      infusion. Antibody blockade of adhesion molecules P-selectin, von Willebrand
      factor (VWF), E-selectin, vascular cell adhesion molecule 1, intercellular
      adhesion molecule 1, platelet endothelial cell (EC) adhesion molecule 1,
      alpha4beta1, or alphaVbeta3 integrin prevented vaso-occlusion. Heme rapidly (5
      minutes) mobilized Weibel-Palade body (WPB) P-selectin and VWF onto EC and vessel
      wall surfaces and activated EC nuclear factor kappaB (NF-kappaB). This was
      mediated by TLR4 as TAK-242 blocked WPB degranulation, NF-kappaB activation, vaso
      occlusion, leukocyte rolling/adhesion, and heme lethality. TLR4(-/-) mice
      transplanted with TLR4(+/+) sickle bone marrow exhibited no heme-induced vaso
      occlusion. The TLR4 agonist lipopolysaccharide (LPS) activated ECs and triggered
      vaso-occlusion that was inhibited by TAK-242, linking hemolysis- and infection
      induced vaso-occlusive crises to TLR4 signaling. Heme and LPS failed to activate
      VWF and NF-kappaB in TLR4(-/-) ECs. Anti-LPS immunoglobulin G blocked LPS
      induced, but not heme-induced, vaso-occlusion, illustrating LPS-independent TLR4
      signaling by heme. Inhibition of protein kinase C, NADPH oxidase, or antioxidant
      treatment blocked heme-mediated stasis, WPB degranulation, and oxidant
      production. We conclude that intravascular hemolysis in SCD releases heme that
      activates endothelial TLR4 signaling leading to WPB degranulation, NF-kappaB
      activation, and vaso-occlusion. 

PMID- 24277080
TI  - Differential regulation of GLT-1/EAAT2 gene expression by NF-kappaB and N-myc in
      male mouse brain during postnatal development.
AB  - The synaptic glutamate level homeostasis is mainly maintained by the astrocytes
      membrane bound glutamate transporter type-1 (GLT-1/EAAT2). Alterations in its
      expression during development and aging and the underlying mechanisms are not
      well studied. Here, we report that NF-kappaB interaction was highest in both
      cerebral and cerebellar cortices at day 15 when compared with that at day 0
      during development, and it further declined significantly in day 45, and remained
      unchanged in 20 and 70 weeks mice. On the other hand, N-myc interaction was
      highest at 0 day which significantly declined at 15-day and interestingly
      remained unaltered at later ages in both the cortices. This age dependent
      reciprocal pattern of NF-kappaB and N-myc interactions with their cognate GLT-1
      promoter sequences was further correlated with GLT-1 protein and transcript
      levels. We found that higher NF-kappaB interaction with its cognate GLT-1
      promoter sequences correlates with up-regulation whereas the higher N-myc
      interaction correlates with down-regulation of GLT-1 expression during postnatal
      developmental age up to 15 day, however, such phenomenon was not found in the
      higher ages from day 45 to 70 weeks. Thus our data suggests a postnatal
      development- and age dependent differential interaction of transcription factors
      NF-kappaB and N-myc to their respective sequences and they act as positive and
      negative regulator, respectively of GLT-1 gene expression in the brain during
      early developmental period in both cerebral and cerebellar cortices which might
      be different in aging of mice.

PMID- 24277082
TI  - Targeted genome modification technologies and their applications in crop
      improvements.
AB  - Recent advances in genome engineering indicate that innovative crops developed by
      targeted genome modification (TGM) using site-specific nucleases (SSNs) have the
      potential to avoid the regulatory issues raised by genetically modified
      organisms. These powerful SSNs tools, comprising zinc-finger nucleases,
      transcription activator-like effector nucleases, and clustered regulatory
      interspaced short palindromic repeats/CRISPR-associated systems, enable precise
      genome engineering by introducing DNA double-strand breaks that subsequently
      trigger DNA repair pathways involving either non-homologous end-joining or
      homologous recombination. Here, we review developments in genome-editing tools,
      summarize their applications in crop organisms, and discuss future prospects. We
      also highlight the ability of these tools to create non-transgenic TGM plants for
      next-generation crop breeding. 

PMID- 24277083
TI  - Translation efficiency of Lea mRNAs in cotton embryos: minor changes during
      embryogenesis and germination.
AB  - In earlier studies, only two major patterns of transcript accumulation were seen
      for 18 late embryogenesis abundant (Lea) gene families in cotton (Gossypium
      hirsutum L.) during embryogenesis and early germination. Each of these gene
      families probably comprises two active alloalleles. The two polypeptides encoded
      by seven of the Lea families can be distinguished, and analysis of their
      translation in vitro indicated that regulation of the homeologous transcript
      abundance was similar in each.In the present study, two-dimensional gel
      electrophoresis of polypeptides synthesized in excised embryos was employed to
      determine if LEA polypeptide synthesis is regulated at the translational level.
      The relative in vivo synthesis rate of each of the two polypeptides of 7 Lea
      families was compared with the relative concentration of their transcripts
      measured earlier by in vitro translation. For 4 families, the relative
      translational efficiencies of the homeologous mRNAs do not change during
      embryogenesis. However, there are changes of 1.5-3-fold in the other 3 families.
      The translation efficiencies of all transcripts of 9 of the Lea family mRNAs in
      vivo can be calculated from the fraction of total protein radioactivity
      incorporated in each LEA polypeptide family and the fractional abundance of Lea
      family transcripts measured by RNA dot hybridization. Lea mRNAs are found to be
      translated at near average rates throughout embryogenesis and early germination.
      These observations suggest that regulation of Lea gene expression at the
      translational level is minor. 

PMID- 24277081
TI  - Immunogenicity of Brugia malayi Abundant Larval Transcript-2, a potential
      filarial vaccine candidate expressed in tobacco.
AB  - KEY MESSAGE: Transgenic tobacco plants with Bm ALT-2, a filarial vaccine
      candidate, were developed. The plant-produced antigen showed immunogenicity on
      par with the E.coli product. Transgenic tobacco plants were developed using
      Brugia malayi Abundant Larval Transcript-2 (Bm ALT-2), a major antigen produced
      from recombinant E.coli found to be experimentally successful as potential
      vaccine candidate against lymphatic filariasis. Results of experiments on the
      transformation and expression of the Bm ALT-2 in tobacco plant to produce plant
      based vaccine are presented here. We have successfully transformed the tobacco
      plant with Bm ALT-2 and confirmed that the plants expressed the filarial protein
      by PCR analysis and Western blotting. The level of expression varied from 50 to
      90 ng/MUg of total soluble protein for ALT-2. Immunization of mice with plant
      extracted protein indicated that the plant-produced protein had immunological
      characteristics similar to the E.coli-produced protein. Antibody titres produced
      by plant-produced recombinant ALT 2-immunized mice were on par with those
      immunized with recombinant protein produced by E.coli. Antibody isotype assay
      showed that plant-produced recombinant ALT-2 induced significant IgG1, whereas
      E.coli-produced recombinant ALT-2 induced IgG3. This result is a step forward
      towards the development of a model eukaryotic system for the production of
      recombinant filarial proteins, which can be utilized to produce therapeutic and
      diagnostic molecules against lymphatic filariasis, a neglected tropical
      infectious disease which has a negative impact on socioeconomic development. In
      addition, this is the first report of the immunogenicity of a plant-derived
      filarial antigen.

PMID- 24277084
TI  - Expression of a soybean beta-conclycinin gene under the control of the
      Cauliflower Mosaic Virus 35S and 19S promoters in transformed petunia tissues.
AB  - A gene encoding the alpha'-subunit of beta-conglycinin was ligated to the 19S and
      35S promoters of Cauliflower Mosaic Virus and introduced into petunia plants on a
      disarmed Ti-plasmid using Agrobacterium tumefaciens. Transformed cells were
      regenerated into whole plants and ummunoreactive polypeptides and hybridizable,
      polyadenylated mRNA were detected in transformed tissues. Expression from the 35S
      promoter was 10 to 50 times greater than expression from the 19S promoter. The
      level of immunodetectable polypeptides was greater in seeds than in leaves or
      callus tissue. In addition, the pattern of alpha'-polypeptide breakdown products
      was distinctive in seeds and leaves. We conclude that in seeds the higher levels
      of the alpha'-polypeptide reflect enhanced stability of this protein. 

PMID- 24277085
TI  - Identification of psbA and psbD gene products, D1 and D2, as reaction centre
      proteins of photosystem 2.
AB  - A recent report (Nanba O, Satoh K: Proc. Natl. Acad. Sci. USA 84: 109-112, 1987)
      described the isolation from spinach of a putative photosystem 2 reaction centre
      which contained cytochrome b-559 and three other electrophoretically resolvable
      polypeptide bands, two of which have molecular weights comparable to the D1 and
      D2 polypeptides. We have used in vivo labelling with radioactive methionine and
      probed with D1 and D2 monospecific antibodies (raised against synthetically
      expressed sequences of the psbA and psbD genes) for specific detection of these
      proteins in a similarly prepared photosystem 2 reaction centre preparation. These
      techniques identified a 32 000 dalton D1 band, a 30 000 dalton D2 band and a 55
      000 dalton D1/D2 aggregate, the latter apparently arising from the detergent
      treatments employed. Digestions with a lysine-specific protease further confirmed
      the identification of the lysine-free D1 polypeptide and also confirmed that the
      D1 molecules in the 55 000 dalton band were in aggregation with other bands and
      not in self-aggregates. The D1 and D2 polypeptides (including the aggregate) are
      considerably enriched in the photosystem two reaction centre preparation compared
      to the other resolved fractions. 

PMID- 24277086
TI  - Differential accumulation of potato tuber mRNAs during the hypersensitive
      response induced by arachidonic acid elicitor.
AB  - Accumulation of messenger RNAs in potato tuber discs was analysed during the
      hypersensitive response induced by treatment with the biotic elicitor arachidonic
      acid. In vitro translation of polysomal poly(A)(+) RNAs indicated that the
      accumulation of some sixteen mRNAs varied following treatment with arachidonic
      acid, and that the level of thirteen of these was increased. Two cDNA closes
      (pSTH-1 and-2) were isolated from a library of elicitor-treated tissue cDNAs.
      Northern blot analysis using these clones as molecular probes indicated that the
      levels of at least two mRNAs were markedly increased after elicitor treatment. In
      hybrid-released translation experiments, each of the cDNA clones selected more
      than one mRNA. Translation of these mRNAs yielded two polypeptides of Mr 45 000
      (for the pSTH-1 clone), and three polypeptides of Me 17 000 (for the pSTH-2
      clone). The low molecular weight polypeptides may correspond to potato
      pathogenesis-related (PR) proteins. 

PMID- 24277087
TI  - Differential changes in the synthesis and steady-state levels of thylakoid
      proteins during bean leaf senescence.
AB  - During senescence of primary bean leaves (Phaseolus vulgaris), there are
      differential changes in the rates at which thylakoid proteins are synthesized. In
      particular, synthesis of the 32 kD herbicide-binding protein continues throughout
      senescence, whereas formation of the alpha and beta subunits of ATPase, the 68 kD
      photosystem I reaction center polypeptide, cytochrome f, cytochrome b6 and the
      structural apoprotein of the lightharvesting chlorophyll protein complex (LHCP)
      declines. Pulse-chase experiments with intact leaves indicated rapid degradation
      of the 32 kD protein, which is consistent with its known rapid rate of turnover.
      This degradation was light-dependent and inhibited by DCMU, and the kinetics of
      degradation were similar for young and senescent membranes. In Coomassie-stained
      gels, the 68 kD reaction center polypeptide of photosystem I, the alpha and beta
      subunits of ATPase and the LHCP were the dominant proteins for all ages of
      membranes. Western blot analysis indicated that cytochrome f and cytochrome b6
      are selectively depleted during senescence. The data have been interpreted as
      indicating that translational disruptions in both the cytoplasmic and
      chloroplastic compartments may contribute to the decline in photosynthetic
      electron transport in the senescing leaf. 

PMID- 24277088
TI  - The 5' flanking DNA of a patatin gene directs tuber specific expression of a
      chimaeric gene in potato.
AB  - A member of the patatin multigene family which encodes the major soluble tuber
      protein was isolated from potato cultivar Desiree. Analysis by strategic
      nucleotide sequencing demonstrated close homology to analogous regions of
      previously isolated patatin genomic clones from different cultivars. A 3.8-kb
      fragment containing the promoter and 5' flanking DNA of the patatin gene was used
      to construct a transcriptional fusion gene with the coding DNA of the bacterial
      chloramphenicol acetyltransferase (CAT) gene and the polyadenylation/termination
      sequences of the nopaline synthase gene (nos). The chimaeric gene was
      reintroduced into potato cultivar Desiree by agrobacterial transformation of
      tissue slices. Regenerated transformed plants showed expression of the chimaeric
      gene (as determined by CAT activity) in tubers, but not in leaves, stems or roots
      of in vitro grown plants. Independent transformants did not show substantial
      variation in the level of induced tuber-specific CAT activity. Thus, information
      contained within 3.8 kb of the 5' flanking DNA of the patatin gene analysed is
      sufficient to direct tuber-specific expression, largely independent of position
      effects. 

PMID- 24277089
TI  - Transcript levels of two adjacent chloroplast genes during mustard (Sinapis alba
      L.) seedling development are under differential temporal and light control.
AB  - Transcript levels of two plastid genes were investigated during early seedling
      development of mustard (Sinapis alba L.) until 96 h after sowing. The two genes,
      which are closely linked and have the same polarity, are the psbA gene encoding
      the Mr 32-35000 herbicide-binding QB-protein of photosystem II and the trnK gene
      encoding plastid tRNA(Lys) (UUU) and potentially an intron-derived maturase
      related protein. By using Northern and dot blot hybridization techniques with
      sensitive RNA probes, the 1.2 kb psbA transcript was found to be present in low
      amounts during the initial phase of seed germination. Thereafter, it increases in
      concentration both in light- and dark-grown seedlings until approximately 48 h
      after sowing. A further increase in psbA transcript concentration during the
      subsequent phase until 96 h was observed in light-grown, but not in dark-grown
      seedlings. The 2.8 kb trnK transcript is one to two orders of magnitude less
      abundant than the psbA transcript throughout the time period investigated. The
      concentration of this transcript is light-independent and shows a transient peak
      level at around 48 h, i.e. at the onset of light-enhanced accumulation of the
      psbA transcript. 

PMID- 24277090
TI  - Import into chloroplasts of a yeast mitochondrial protein directed by ferredoxin
      and plastocyanin transit peptides.
AB  - Many chloroplast proteins are synthesized in the cytoplasm as precursors which
      contain an amino terminal transit peptide. These precursors are subsequently
      imported into chloroplast and targeted to one of several organellar locations.
      This import is mediated by the transit peptide, which is cleaved off during
      import. We have used the transit peptides of ferredoxin (chloroplast stroma) and
      plastocyanin (thylakoid lumen) to study chloroplast protein import and intra
      organellar routing toward different compartments. Chimeric genes were constructed
      that encode precursor proteins in which the transit peptides are linked to yeast
      mitochondrial manganese superoxide dismutase. Chloroplast protein import and
      localization experiments show that both chimeric proteins are imported into the
      chloroplast stroma and processed. The plastocyanin transit sequence did not
      direct superoxide dismutase to the thylakoids; this protein was found in the
      stroma as an intermediate that still contains part of the plastocyanin transit
      peptide. The organelle specificity of these chimeric precursors reflected the
      transit peptide parts of the molecules, because neither the ferredoxin and
      plastocyanin precursors nor the chimeric proteins were imported into isolated
      yeast mitochondria. 

PMID- 24277092
TI  - Homology between chitinases that are induced by TMV infection of tobacco.
AB  - Recently, four chitinases have been detected in tobacco mosaic virus (TMV)
      infected tobacco: two acidic chitinases that were identified as pathogenesis
      related (PR) proteins P and Q and two basic chitinases (Legrand et al.,
      Proc.Natl. Acad. Sci. USA, in press). Here, it was shown that P and Q are closely
      serologically related but not related to other known acidic tobacco PR proteins.
      Antisera to P and Q were used to characterize translation products of TMV-induced
      mRNAs that were hybrid-selected with cDNA clones described previously (Hooft van
      Huijsduijnen et al., EMBO J 5: 2057-2061, 1986). In this way cDNA clones
      corresponding to the acidic and basic chitinases were identified. The partial
      amino acid sequences of the acidic and basic tobacco chitinases that were
      represented in the clones, showed an approximately 70% homology to each other and
      to the sequence of a bean chitinase. Although the acidic and basic chitinases
      differ in apparent molecular weight, they were found to have homologous C
      termini.Hybridization of cDNA probes to genomic blots indicated that the acidic
      and basic chitinases are each encoded by two to four genes in the amphidiploid
      genome of Samsun NN tobacco. A similar complexity was found for the genes
      encoding the tobacco PR protein that is homologous to the sweet-tasting protein
      thaumatin and to the bifunctional trypsin/alpha-amylase inhibitor from maize. 

PMID- 24277093
TI  - Editor's note.

PMID- 24277094
TI  - Plant polyphenols (syn. vegetable tannins) and chemical defense-A reappraisal.
AB  - Many of the hypotheses adumbrated to rationalize the role of natural products in
      plant-herbivore interactions have focused attention on plant polyphenols (syn.,
      vegetable tannins). Contemporary interpretations of the importance of plant
      polyphenols rest largely on the assumption that they act via their capacity to
      bind to proteins. The central proposition of plant-herbivore interactions, namely
      that plants, as a response to environmental pressures, have evolved the strategem
      of a chemical armory appropriate to the challenges they face, is examined in the
      context of plant polyphenols-their ability to complex to protein and their
      possible function as structural polymers. 

PMID- 24277091
TI  - Plant gene expression in response to pathogens.

PMID- 24277095
TI  - Periplaneta americana perception of phytochemical naphthoquinones as
      allelochemicals.
AB  - Electrochemistry of malePeriplaneta americana perception of naphthoquinones as
      allelochemicals is presented. Importance of the oxidation-reduction potential and
      hydrogen-bonding capabilities of the naphtho-quinone messenger to its exchange of
      energy with the information-encoding, redox protein of the chemosensory neuron is
      considered. Evidence that the required information is initially encoded by an
      electroreactive protein in dendritic membrane is analyzed. A sulfhydryl-disulfide
      protein-based electrochemical mechanism for the demonstrated linear conversion of
      a molecular messenger energy state into whole insect behavior (avoidance or
      feeding inhibition) is elucidated. Even though the information-encoding mechanism
      is genetically conserved (kept electrochemically similar) within the species,
      behavioral biotypical differences regarding sensitivity to naphthoquinones are
      allowed through a group of proteins in the outer aqueous medium in the
      chemosensory sensillum. Such proteins electrochemically interface the dendritic
      membrane of the chemosensory neuron in the sensillum with the environment
      external to the sensillum. These interfacing proteins bind (complex) with
      chemical messengers (e.g., naphthoquinones) and/or variously degrade them, and
      thus determine the amount (moles) that is required in the environment to result
      in stimulation of the underlying sensory neurons and in a changed behavior. 

PMID- 24277096
TI  - Bioassay of naturally occurring allelochemicals for phytotoxicity.
AB  - The bioassay has been one of the most widely used tests to demonstrate
      allelopathic activity. Often, claims that a particular plant species inhibits the
      growth of another are based entirely on the seed germination response to solvent
      extracts of the suspected allelopathic plant; few of these tests are of value in
      demonstrating allelopathy under natural conditions. The veracity of the bioassay
      for evaluating naturally occurring compounds for phytotoxicity depends upon the
      physiological and biochemical response capacity of the bioassay organism and the
      mechanism(s) of action of the allelochemicals. The possibility that more than one
      allelochemical, acting in concert at very low concentrations, may be responsible
      for an observed allelopathic effect makes it imperative that bioassays be
      extremely sensitive to chemical growth perturbation agents. Among the many
      measures of phytotoxicity of allelochemicals, the inhibition (or stimulation) of
      seed germination, radicle elongation, and/or seedling growth have been the
      parameters of choice for most investigations. Few of these assays have been
      selected with the view towards the possible mechanism of the allelopathic effect.

PMID- 24277097
TI  - Potentials for exploiting allelopathy to enhance crop production.
AB  - Strategies for utilizing allelopathy as an aid in crop production include both
      avoidance and application protocols. There are immediate opportunities for
      management of weed and crop residues, tillage practices, and crop sequences to
      minimize crop losses from allelopathy and also to use allelopathic crops for weed
      control. Varieties of grain and forage sorghums (Sorghum Spp.), sunflower
      (Helianthus annuus L.), oats (Avena sativa L.), wheat (Triticum sativum L.),rye
      (Secale cereale L.), and others may provide weed control and in some instances
      crop stimulation from their residues. Our four-year field study with cultivated
      sunflower resulted in no differences in weed biomass between plots with and
      without herbicide (EPTC) applications. Strip cropping that included sorghum
      showed that in the subsequent year weed density and biomass were significantly
      lower in the previous-year sorghum than in soybean strips. Possibilities exist
      for modification of crop plant metabolism to alter production of allelochemicals.
      Allelochemical-environmental interactions must be considered in efforts to
      benefit from allelopathy. Under greenhouse conditions, joint application of low
      levels of atrazine, trifluralin, alachlor, or cinmethylin with a phenolic
      allelochemical showed that these two categories of inhibitors acted in concert to
      reduce plant growth. Allelochemicals may also be adapted as yield stimulants or
      environmentally sound herbicides, such as cinmethylin and methoxyphenone.
      Isolation of bialophos, tentoxin, and others shows that bacteria and fungi are
      good sources of biologically active compounds. 

PMID- 24277098
TI  - Activity of drimane antifeedants and related compounds against aphids, and
      comparative biological effects and chemical reactivity of (-)- and (+)
      polygodial.
AB  - A series of natural drimanes and related synthetic compounds was tested for
      antifeedant activity against aphids. Polygodial and warburganal were the most
      active. The synthetic compounds methyl 9alpha-hydroxydrimenoate and 9alpha
      hydroxydrimenal, although active against lepidopteran larvae, were inactive
      against aphids. Natural (-)-polygodial and the synthetic (+) isomer showed
      similar levels of activity as aphid antifeedants and in phytotoxicity, fish
      toxicity, and human taste tests, but reacted at different rates with enantiomers
      of 1-phenylethylamine. 

PMID- 24277099
TI  - Application of sex attractants for monitoring the pea moth,Cydia nigricana (F.)
      (Lepidoptera: Tortricidae).
AB  - The use of sex attractants to monitor the pea moth,Cydia nigricana (F.) in the
      United Kingdom is decribed. Two systems are currently available: one for use in
      combining (dry-harvested) peas for human consumption or seed, and one for use in
      vining peas for freezing or canning. The development and details of both systems
      are reviewed and their commercial application discussed. 

PMID- 24277100
TI  - Adaptive relationships of epoxide hydrolase in herbivorous arthropods.
AB  - Epoxide hydrolase catalyzes a simple hydrolysis of reactive cyclic ethers that
      may otherwise alkylate and impair critical proteins and nucleic acids required
      for life. Although much less studied than the cytochrome P-450 monooxygenases
      that produce epoxides, differences in subcellular, tissue, pH, substrate, and
      inhibitor specificities argue for at least three forms of insect epoxide
      hydrolase. Increasing numbers of epoxides are being identified as plant
      allelochemicals, antifeedants, and essential hormones or precursors for
      herbivorous arthropods, and in many cases an associated alkene to diol pathway of
      metabolism is found. A role for epoxide hydrolase in arthropod-plant interactions
      is strongly supported by species comparisons and by age-activity and induction
      studies. Two major limitations for study in biochemical ecology of epoxide
      hydrolase are the lack of an effective in vivo inhibitor and a range of
      commercially available radiolabeled substrates for the enzymes. 

PMID- 24277101
TI  - Bullfinches and ash trees : Assessing the role of plant chemicals in controlling
      damage by herbivores.
AB  - Wild bullfinches (Pyrrhula pyrrhula) feed heavily on the seeds of ash trees
      (Fraxinus excelsior). Field and laboratory studies show that individual trees
      with high levels of fat and low levels of phenolic chemicals in their seeds are
      especially liable to predation. This paper discusses (1) the complexity of
      effects that need to be examined in order to identify the role of secondary
      chemicals in determining herbivore preferences, and (2) the consequences of seed
      predation for the dispersal of seeds. Because of bullfinches' habits, and the
      many factors influencing seed dispersal and germination, it is not clear whether
      the birds' activities are necessarily damaging. This study emphasises the value
      of understanding the whole ecology of both plants and herbivores in order to
      interpret their interactions. 

PMID- 24277102
TI  - Chemical ecology and the search for marine antifoulants : Studies of a predator
      prey symbiosis.
AB  - The gorgonian octocoralLeptogorgia virgulata (Phylum Coelenterata, Class
      Anthozoa) is rarely overgrown by fouling organisms and is avoided by most
      predators. Laboratory experiments suggest that secondary metabolites and calcium
      carbonate spicules interact synergistically to provideL. virgulata with an
      effective defense against predatory fish. In spite of these defenses,L. virgulata
      is consumed by the symbiotic, trophically specialized gastropodNeosimnia
      uniplicata, which closely mimics the appearance of the gorgonian.Neosimnia
      uniplicata is readily eaten by fish and appears not to acquire an effective
      antipredator defense from its gorgonian host. Extracts ofLeptogorgia virgulata
      andNeosimnia uniplicata strongly inhibited the settlement of the barnacleBalanus
      atnphitrite. Bioassay-directed purification of the more potent antifouling agents
      fromL. virgulata led to the isolation of two previously described, diterpenoid
      hydrocarbons, known as pukalide and epoxypukalide. A third inhibitor of barnacle
      settlement, whose structure is presently unknown, was obtained from bothL.
      virgulata andN. uniplicata. When assayed for ability to inhibit barnacle
      settlement, these three compounds possessed EC50 values ranging from 19 to 55
      ng/ml. These secondary metabolites may prevent the overgrowth ofL. virgulata by
      fouling organisms in nature. The allelochemicals ofL. virgulata, N. uniplicata,
      and other marine organisms may provide nonpolluting alternatives to existing,
      commercial antifoulants based on derivatives of tri-n-butyltin. 

PMID- 24277103
TI  - Enzymic adaptations in leaf-feeding insects to host-plant allelochemicals.
AB  - Herbivorous insects have the capacity to develop behavioral, physiological, and
      biochemical resistance mechanisms in response to chemical selection pressures.
      Among natural insect-plant associations, there are several cases of target-site
      insensitivity to and enhanced metabolism of plant allelochemicals. There are also
      known instances of physiological defenses such as extra rapid excretion or
      storage of toxic compounds. Multiple defenses seem to be prevalent in natural
      insect-plant interactions that involve toxic compounds, possibly reflecting the
      long time these interactions have had to evolve compared to insect-synthetic
      insecticide interactions. Synthetic insecticides were introduced about 45 years
      ago. Until recently they have been used as single-active-component preparations.
      As such, they have been and are very effective in producing insect populations
      with enhanced detoxification ability and target-site insensitivity. Most
      insecticide-resistant insect populations have one major defense mechanism. This
      feature makes the synthetic insecticides very useful tools for studies of insect
      defenses against toxic chemicals. Information gained from studies with
      insecticides can shed light on the capabilities of insects to adapt to toxicants
      in their environment. In assessing the validity of work with synthetic
      insecticides for natural systems, the fundamental differences between these
      substances and allelochemicals, and in their presentation to the insects, must,
      however, be considered. The prevalence of multiple defenses and reliance on
      modified physiological processes in natural interactions may reflect different
      properties of the natural chemicals in being generally highly biodegradable and
      often less acutely toxic than synthetic insecticides. In many cases, the plant
      allelochemicals are presented to the insects as mixtures. It is, however, to be
      expected that pest insects will evolve effective multiple defenses against
      synthetic insecticides. About 20% of all resistant populations have already
      developed multiple defenses, in most cases combinations of enhanced metabolism
      and target-site insensitivity. This implies that current crop protection
      practices need to be modified to ensure the continued usefulness of synthetic
      insecticides. To achieve this, it is important to study intensively not only
      insect-insecticide interactions but also the interactions operating in natural
      insect-plant associations. 

PMID- 24277104
TI  - Bioassays of segregating plants : A strategy for studying chemical defenses.
AB  - Solanum chacoense is a wild potato species resistant to the Colorado potato
      beetle,Leptinotarsa decemlineata. Most genotypes ofS. chacoense synthesize the
      glycoalkaloids solanine (sol) and chaconine (chac) and are hosts of the beetle. A
      few rare genotypes have a gene(s) for acetylation of carbon-23 of the steroid
      aglycone of sol and chac. Laboratory bioassays and replicated field tests of
      clones differing in the presence or absence of the acetyl moiety showed that
      acetylation of sol and chac markedly affects the response of both adults and
      larvae to the foliage. Adult feeding deterrency conferred by acetylated forms of
      sol and chac (leptines) in leaf-disk preference tests was consistent with the
      degree of antixenosis measured in the field. Development of larvae on foliage of
      clones with leptines was also inhibited. The studies support the validity of
      using laboratory bioassays of plants segregating for levels of a suspected
      defense compound to determine the role the compound has in defending the plant
      from attack by an insect predator in the field. 

PMID- 24277105
TI  - Bioassay techniques : An ecological perspective.
AB  - Research in plant-herbivore interactions relies heavily on bioassays as
      analytical tools. Successful bioassay experiments are difficult to design because
      of the need to reconcile the exacting requirements of hypothesis testing with the
      dynamic nature of the plant and insect test organisms. Several research protocols
      are discussed that utilize ecologically flawed techniques to answer ecologically
      important questions. 

PMID- 24277106
TI  - Plant-insect coevolution and inhibition of acetylcholinesterase.
AB  - The theory of plant-insect coevolution provides for diffuse coevolution and the
      expectation that plants evolve broad-spectrum chemical defenses with which some
      insects coevolve by detoxifying and using the compounds as host-location cues.
      Specific biochemical modes of action have been assigned to relatively few such
      defense chemicals and one major class, the terpenoids, is investigated here. Six
      terpenoids inhibited the enzyme acetylcholinesterase (derived from electric eel)
      and elicited the appropriate in vivo effects of insect paralysis and mortality.
      The diterpene gossypol was a reversible uncompetitive inhibitor. Five
      monoterpenes, representing a range of functional groups, were reversible
      competitive inhibitors apparently occupying at least the hydrophobic site of the
      enzyme's active center. Such data suggest the involvement of acetylcholinesterase
      in the coevolved insect response to terpenoids. 

PMID- 24277107
TI  - Astringency of Douglas-fir foliage in relation to phenology and xylem pressure
      potential.

PMID- 24277108
TI  - Age of sex reassignment surgery for male-to-female transsexuals.

PMID- 24277110
TI  - Relationship of abdominal circumference and trunk length with spinal anesthesia
      level in the term parturient.
AB  - BACKGROUND: We hypothesized that body shape metrics influence the anatomy of
      spinal canal and intraabdominal pressure in three dimensions. We explored the
      effects of abdominal circumference, trunk length, and their combination on the
      level of spinal anesthesia in the term parturient in this study. METHODS: Thirty
      term parturients, ASA class I-II, from 20 to 41 years of age, scheduled for
      cesarean section were enrolled in this observational study. Abdominal
      circumference (AC) and trunk length (TL) were recorded preoperatively. Spinal
      anesthesia was performed with 10 mg 0.5% hyperbaric bupivacaine at the L4-L5
      intervertebral space in all parturients. Correlation between maximal sensory
      spinal anesthesia level and physical parameters was analyzed with Spearman rank
      correlation coefficients. The calculated r value was compared with r = 0 with p <
      0.05 as the significant level. The prediction power of these physical parameters
      for spinal level was evaluated by prediction probability. RESULTS: The parameter
      TL/AC2 was statistically correlated with maximal sensory level (Spearman
      correlation coefficient, -0.45 with p < 0.02). The prediction probability of
      TL/AC2 for the dermatomal level was P K = 0.685. If the dermatomal levels were
      lumped as higher (above T2) and lower (below T3) levels, the prediction
      probability of TL/AC2 was as high as P K = 0.856. CONCLUSIONS: TL/AC2, which
      simulated the ratio of the long axis and transection area of the abdomen, was
      correlated with maximal spinal level, and parturients with low TL/AC2 values
      tended to have higher dermatomal levels during spinal anesthesia.

PMID- 24277109
TI  - Interest in couples-based voluntary HIV counseling and testing in a national U.S.
      sample of gay and bisexual men: the role of demographic and HIV risk factors.
AB  - Main partnerships represent one context in which HIV transmission may occur that
      has been insufficiently addressed to date for gay and bisexual men, but few
      studies have focused on the acceptability of couples-based voluntary HIV
      counseling and testing (CVCT) for male couples in the U.S. Our aim in this study
      was to explore the acceptability of CVCT among a national U.S. sample of 1,532
      gay and bisexual men surveyed online using a sexual networking site. We examined
      the role of demographic (i.e., geographic region, age, relationship status,
      sexual orientation, race/ethnicity) and HIV risk (i.e., substance use, number of
      sexual partners, unprotected anal intercourse, sexual role identity, and sexual
      compulsivity) factors that may be associated with CVCT among the full sample and
      among partnered men separately. We found that single men expressed higher
      interest in CVCT than partnered men and that greater age was more strongly
      associated with lower interest in CVCT for partnered men than for single men. The
      intersection of sexual orientation and race/ethnicity was also significantly
      associated with CVCT interest, with a higher proportion of Black bisexual men
      being interested than White bisexual men. These findings suggest that the uptake
      of CVCT may be less impacted by HIV risk factors than by demographic factors and
      that young gay and bisexual men of color-for whom rates of HIV continue to rise
      may be the group with the highest levels of interest in CVCT. 

PMID- 24277111
TI  - From the Journal archives: Postoperative analgesia: effect on lung volumes.
AB  - This study was undertaken to determine the contribution of postoperative pain to
      the known changes that occur to respiratory function in the postoperative period.
      The authors studied changes in functional residual capacity (FRC) and vital
      capacity (VC) either in the postanesthesia care unit or on postoperative day one
      in eight relatively healthy adult patients having upper abdominal surgery. These
      values were compared with measurements immediately before surgery. Variables were
      measured postoperatively during pain and then again after establishment of
      epidural analgesia. Epidural analgesia to a T4 sensory level resulted in a
      partial and statistically significant restoration of VC (from 37-55% of
      preoperative values) and a partial but statistically insignificant restoration of
      FRC (from 78-84% of preoperative values). The authors suggest that postoperative
      epidural analgesia may be able to decrease respiratory complications. AUTHORS:
      Wahba MW, Don HF, Craig DB. Can Anaesth Soc J 1975; 22: 519-27. PURPOSE: This
      study was undertaken to determine the contribution of postoperative pain to the
      known changes that occur to respiratory function in the postoperative period.
      PRINCIPAL FINDINGS: Epidural analgesia to T4 resulted in a partial and
      statistically significant restoration of VC (from 37-55% of preoperative values)
      and a partial but statistically insignificant restoration of FRC (from 78-84% of
      preoperative values). CONCLUSION: Epidural analgesia has more effect on the
      voluntary aspects of postoperative respiration (VC) than on the involuntary
      changes in respiration (FRC) after upper abdominal surgery.

PMID- 24277112
TI  - From the Journal archives: Understanding the mechanism(s) regulating hypoxic
      pulmonary vasoconstriction: how an early study has led to novel translational
      approaches.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is a fundamental physiological process
      whereby ventilation/perfusion matching is optimized through the constriction of
      the pulmonary circulation supplying poorly ventilated lung units. In their 1981
      paper in the Journal, Noble, Kay, and Fisher used a series of animal experiments
      to show that alveolar carbon dioxide (CO2) plays a critical role in the
      regulation of hypoxic pulmonary vasoconstriction. At physiological
      concentrations, CO2 potentiates the HPV response, and the absence of alveolar CO2
      blunts HPV. The enhancement of HPV by CO2 resulted in reduced perfusion of
      specific hypoxic lung regions, thereby improving systemic oxygenation in lung
      ventilated dogs. AUTHORS: William H. Noble, J. Colin Kay, Joseph A. Fisher
      CITATION: Can Anaesth Soc J 1981; 28: 422-30. PURPOSE: To determine the dominant
      effect of variations in alveolar carbon dioxide tension on hypoxic pulmonary
      vasoconstriction. PRINCIPAL FINDINGS: The group found that 1) increasing alveolar
      carbon dioxide concentrations enhanced hypoxic pulmonary vasoconstriction; 2)
      this enhancement improved oxygenation in ventilated dogs with regional alveolar
      hypoxia; and 3) this enhanced oxygenation was not due to increased cardiac
      output. CONCLUSIONS: Increased alveolar carbon dioxide enhances hypoxic pulmonary
      vasoconstriction. In clinical scenarios where hypoventilated or hypoxic lung
      regions exist, e.g., one-lung ventilation or lung consolidation, permissive
      hypercapnea may improve oxygenation.

PMID- 24277113
TI  - The transition from acute to chronic pain: understanding how different biological
      systems interact.
AB  - PURPOSE: Although pain is an adaptive sensory experience necessary to prevent
      further bodily harm, the transition from acute to chronic pain is not adaptive
      and results in the development of a chronic clinical condition. How this
      transition occurs has been the focus of intense study for some time. The focus of
      the current review is on changes in neuronal plasticity as well as the role of
      immune cells and glia in the development of chronic pain from acute tissue injury
      and pain. PRINCIPAL FINDINGS: Our understanding of the complex pathways that
      mediate the transition from acute to chronic pain continues to increase. Work in
      this area has already revealed the complex interactions between the nervous and
      immune system that result in both peripheral and central sensitization, essential
      components to the development of chronic pain. Taken together, a thorough
      characterization of the cellular mechanisms that generate chronic pain states is
      essential for the development of new therapies and treatments. Basic research
      leading to the development of new therapeutic targets is promising with the
      development of chloride extrusion enhancers. It is hoped that one day they will
      provide relief to patients with chronic pain. CONCLUSIONS: A better understanding
      of how chronic pain develops at a mechanistic level can aid clinicians in
      treating their patients by showing how the underlying biology of chronic pain
      contributes to the clinical manifestations of pain. A thorough understanding of
      how chronic pain develops may also help identify new targets for future analgesic
      drugs.

PMID- 24277114
TI  - Reversible cerebral vasoconstriction syndrome (RCVS) in antiphospholipid antibody
      syndrome (APLA): the role of centrally acting vasodilators. Case series and
      review of literature.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is Raynaud's phenomenon of
      the brain. Changes in neurological function are dependent upon which areas of the
      brain are deprived of normal blood flow. Antiphospholipid antibody syndrome
      (APLA) is a common cause of Raynaud's phenomenon that can occur anywhere in the
      body, including the brain. Management of CNS vasospasm generally involves the use
      of centrally acting calcium channel blockers, which have been shown to relieve
      the associated headaches and transient neurological symptoms associated with it.
      Three patients with APLA and RCVS from our clinics are illustrated. It is
      demonstrated that the use of centrally acting calcium channel-blocking drugs,
      such as nimodipine, which prevent and reverse CNS vasospasm, led to clinical
      improvement in our patients over the course of 5-9 years. All of them had MRIs
      done at the initiation of therapy and 5-9 years after being on therapy. MRI
      measures of T2 lesion volumes (LVs) and number were obtained. All three patients
      had a good response in controlling clinical symptoms related to CNS vasospasm,
      Raynaud's phenomenon, visual disturbances, confusion, headaches, and hearing
      loss. There was also a resolution in the MRI findings of these patients. This
      case series of three patients shows a clinical improvement and decrease in T2 LV
      and number in patients with APLA and Raynaud's syndrome on centrally acting
      calcium channel blockers. RCVS is much more common than that currently
      appreciated. APLA is the common cause of RCVS. Further studies are needed to
      determine the optimal methods to diagnose RCVS and optimal therapies to treat it.

PMID- 24277115
TI  - Outcomes and cost-effectiveness of carpal tunnel injections using sonographic
      needle guidance.
AB  - This randomized controlled study addressed whether sonographic needle guidance
      affected the outcomes of corticosteroid injection for symptomatic carpal tunnel
      syndrome. Seventy-seven symptomatic carpal tunnels were randomized to injection
      by either (1) conventional anatomic landmark palpation-guided injection or (2)
      sonographic image-guided injection, each using a two-step technique where 3 ml of
      1% lidocaine was first injected to hydrodissect and hydrodisplace critical intra
      carpal tunnel structures followed by injection with 80 mg of triamcinolone
      acetonide (2 ml). Baseline pain, procedural pain, pain at outcome (2 weeks and 6
      months), responders, therapeutic duration, total cost, and cost per responder
      were determined. There were no complications in either treatment group. Relative
      to conventional anatomic landmark palpation-guided methods, sonographic guidance
      for injection of the carpal tunnel resulted in 77.1% reduction in injection pain
      (p<0.01), a 63.3% reduction in pain scores at outcome (p<0.014), 93.5% increase
      in the responder rate (p<0.001), 84.6% reduction in the non-responder rate
      (p<0.001), a 71.0% increase in therapeutic duration (p<0.001), and a 59.3% ($150)
      reduction in cost/responder/year for a hospital outpatient (p<0.001). However,
      despite improved outcomes, cost per patient per year was significantly increased
      for an outpatient in a physician's office and was neutral for a hospital
      outpatient. Sonographic needle guidance significantly improves the performance
      and clinical outcomes of injection of the carpal tunnel and is cost-effective for
      a hospital-based practice, but based on current reimbursements, it significantly
      increases overall costs for medical care delivered in a non-hospital-based
      physician practice.

PMID- 24277116
TI  - Elderly subset analysis of randomized phase III study comparing pemetrexed plus
      carboplatin with docetaxel plus carboplatin as first-line treatment for patients
      with locally advanced or metastatic non-small cell lung cancer.
AB  - BACKGROUND: Many physicians consider platinum-doublet chemotherapy inappropriate
      for elderly patients, regardless of their medical fitness. OBJECTIVE: This was a
      retrospective subgroup analysis of data from a multicenter, randomized, phase III
      clinical trial evaluating pemetrexed + carboplatin versus docetaxel + carboplatin
      in elderly chemo-naive patients with advanced, nonsquamous non-small cell lung
      cancer (NSCLC). METHODS: Data from elderly patients (aged >=65 years and >=70
      years) were evaluated using the same statistical methods as those used in
      patients aged <70 years and qualified intent-to-treat (Q-ITT) populations. The
      primary objective of the clinical trial was comparison of pemetrexed +
      carboplatin with docetaxel + carboplatin in terms of survival without grade 3 or
      4 toxicity in chemo-naive NSCLC patients. RESULTS: The >=65- and >=70-year age
      groups had 68 and 37 patients, respectively. Among patients aged >=65 years, the
      adjusted hazard ratio (HR) for survival without grade 3-4 toxicity (HR 0.40, 95 %
      confidence interval [CI] 0.23-0.70) favored pemetrexed + carboplatin; this was
      similar to the HRs in patients aged >=70 years (HR 0.43, 95 % CI 0.20-0.92),
      patients aged <70 years (HR 0.44, 95 % CI 0.32-0.62), and the Q-ITT population
      (HR 0.45, 95 % CI 0.34-0.61). The median values for overall survival (OS) and
      progression-free survival (PFS) were similar across all age-group subsets and the
      Q-ITT population. The HRs for OS and PFS were similar for all age-group subsets,
      except for the >=70-year age group, which favored pemetrexed + carboplatin to a
      greater extent. The toxicity profile was similar across age groups, with the
      exception of diarrhea, mucosal inflammation, and grade 3-4 neutropenia and
      leukopenia, which were slightly more common in elderly patients in both treatment
      arms. Between-arm differences in the toxicity profiles for the >=65-, >=70- and
      <70-year age subgroups were similar to those in the Q-ITT population. There were
      no on-study deaths or unexpected toxicities. CONCLUSION: The benefits of
      pemetrexed + carboplatin were maintained, and toxicity was manageable in both
      elderly subgroups. The favorable risk-benefit profile of pemetrexed + carboplatin
      makes it an appropriate first-line treatment option for elderly patients with
      advanced nonsquamous NSCLC.

PMID- 24277117
TI  - Epidemiology of hemopoietic system neoplasms in Argentina.
AB  - The mortality caused by blood neoplasms in Argentina shows great irregularity.
      This was found to be caused in certain ways by (a) differences in the sexes and
      ages of the populations studied; (b) differences in available health services;
      and (c) environmental factors. Thus high rates and clusters of lymphomas and
      multiple mylomas were observed in zones with arsenical water, for example.In
      rural districts, the rates are lower, especially among old-aged people.Lower
      rates of leukemias were also observed among Spaniards compared to Italians
      (p=0.001) residing in Argentina. Turkish, Syrian, and Lebanese showed higher
      rates than Argentinians, Spaniards, or Italians.The results of a case-control
      study are given in which the following were observed: (a) Among the ancestors of
      cases HSN there are fewer Spaniards (not significant) and Latin-Americans
      (p=0.03) and more people who were born in Central or Eastern Europe (p=0.01). (b)
      In case group, there was more frequent contact with animals, especially dogs; and
      a greater exposure to petroleum and its products, and to insecticides. 

PMID- 24277118
TI  - Copper and zinc metabolism with solid tumor growth.
AB  - The variation in copper and zinc metabolism with tumor growth appears to relate
      directly to progression or regression of the disease. Historically, elevations in
      serum copper have been used as clinical indicators in hematological neoplasms
      since the early 1960s. More recently, we have monitored breast, colo-rectal, and
      lung cancer patients for a six-month period through courses of cytotoxic
      chemotherapy to determine copper and zinc changes with tumor growth. Groups were
      divided into responders and nonresponders blind to their serum copper and zinc
      levels. Trends in elevated serum copper with active disease have shown similar
      trends in decreasing values with effective therapy, but normalization was at a
      slower rate. Serum zinc levels in the same patients were markedly below normal
      and did not increase in the study period. The clinical significance or elevated
      serum copper and depressed serum zinc is discussed and the potential relationship
      between the two elements is explored. A solid tumor-bearing rat model, mammary
      adenocarcinoma R 3230 AC, has detailed more of the changes in copper and zinc
      metabolism with solid tumor growth. Serum copper and zinc varied with tumor mass,
      as in clinical studies. Liver values of the two essential metals did not change
      significantly, but liver-related copper-containing enzymes showed marked
      variations. Ceruloplasmin in serum increased with increasing tumor mass, as would
      be expected with the increased serum copper levels. Cytochrome c oxidase activity
      in liver homogenates from tumor-bearing animals was significantly depressed. 

PMID- 24277119
TI  - Thymic lymphosarcoma in magnesium-deficient rats.
AB  - Dietary magnesium deficiency in rats for a minimum period of 40 days evokes
      typical cellular changes in the peripheral blood and the bone marrow; among
      survivors, 40% develop a thymic tumor. The growths were found irreversible in
      animals returned to a normal equilibrated diet. Histologic and ultrastructural
      studies indicated that we were dealing with a thymic lymphosarcoma. We noted the
      presence of virus-like particles in the cytoplasm of the tumor cells, but our
      investigations would favor the idea that these minute structures correspond to
      degradation products in an autophagic vacuole as part of the involute process of
      the neoplastic cells. 

PMID- 24277120
TI  - Trace element profiles in cancer patients.
AB  - It has become evident over the last two decades that there is an intimate
      relationship between the trace elements and cancer. Some trace elements have been
      shown to be carcinogens, others appear to provide protection against cancer.
      Profound changes in trace element concentrations and distribution occur in
      patients with cancer, but most changes remain undefined.A review of a number of
      studies of trace element changes in patients with cancer demonstrates that simple
      correlations of trace element levels in disease are of only limited use. Such
      reports underscore the need for large-scale studies that consider the many
      variables of malignancies and of trace element chemistry. The variables that must
      be considered for cancer include tissue of origin; histologic, pathologic and
      clinical staging; nutritional status as reflected by serum levels of calcium,
      iron, magnesium, phosphorus, the electrolytes, pH, albumen, and globulin;
      endocrine balance, effects of previous and concurrent therapies such as surgery,
      chemotherapy, hormonal manipulation, immunotherapy, and radiotherapy; history of
      exposure to toxic agents; and the presence of other disease.Similarly, trace
      element studies entail variables that must be considered and controlled
      prospectively, including timing and techniques of sampling, storage, and
      analysis, and simultaneous measurement of at least the majority of possibly
      interrelated elements rather than studying one element at a time.The various
      national cooperative oncology groups such as ECOG, SWOG, and SEOG now offer
      unusually well-studied groups of cancer patients who are managed according to
      carefully and prospectively defined protocols in participating institutions. With
      present knowledge, it is now time to approach these groups with a proposal to
      incorporate trace element studies in their protocols. A potential protocol will
      be discussed. 

PMID- 24277121
TI  - The metabolism of selenite and selenomethionine in mouse fibroblasts grown in
      tissue culture.
AB  - Recent reports have provided evidence that selenium is an essential growth factor
      for cells grown in tissue culture. The aim of the work reported in this paper was
      to evaluate mouse fibroblasts as a model for the study of selenium metabolism in
      mammalian cells.The results showed that transformed mouse lung fibroblasts grown
      in media containing 9.1% bovine serum did not show a growth response to added
      selenium as selenite over the range of 10-1000 ng/mL. Uptake of selenium by cells
      was a direct function of the selenium concentration in the medium. The rate of
      uptake varied with the time of exposure of the cells to the selenium, and to the
      form of selenium in the medium.Experiments using radioactive selenium showed
      that(75)Se from selenite was rapidly absorbed into the cell wall, but slowly
      incorporated into the soluble protein fraction.(75)Se from selenomethionine was
      more slowly absorbed into the cells, but once inside, it became rapidly
      incorporated into soluble cytoplasmic proteins.Cell fractionation and gel
      filtration procedures established that(75)Se from selenite was rapidly
      incorporated into glutathione peroxidase (GSHpx), whereas(75)Se from
      selenomethionine was initially incorporated into a wide spectrum of proteins and
      only after a longer period did the(75)Se peak become associated with GSHpx.These
      findings suggest fundamental differences exist in the manner in which mammalian
      cells initially absorb and metabolize different selenium compounds. 

PMID- 24277122
TI  - The newer trace elements.
AB  - The application of the concept of a "controlled environment" led to the
      identification of eight trace elements with a proven or postulated biological
      function during this decade. Rigorous reduction of metallic contamination from
      air, drinking water, and diet is necessary to reduce exposure to the element
      under investigation below requirement levels. An essential function for a trace
      element is suggested when deficiency is produced, and indepently confirmed, in
      two or more animal species, and also when the signs of deficiency are prevented
      or cured by supplements. As yet, a direct role for the "new trace elements" in
      the human organism has not been demonstrated. 

PMID- 24277123
TI  - Toward a global ethic.

PMID- 24277124
TI  - Religious development: A synthesis and reformulation.
AB  - Based on developmental psychology, recent theories of religious development have
      led to proposed stage models of individual spiritual striving. However, these
      models omit the contributions of psychoanalytic psychology to the understanding
      of religious functioning. The schema presented in this article reformulates
      current models of faith development in light of insights from psychodynamic and
      object relations theory. Description of the fifth stage, the highest level of
      religious development, represents a composite of the literature on religious
      maturity. The first objective of this synthesis and reformulation is to offer
      descriptive criteria by which psychotherapists can discriminate a healthy from an
      unhealthy religious outlook. The second is to illuminate the intrapsychic
      dynamics underlying unhealthy religiousness in adults. Such a conceptual
      framework should assist psychotherapists working with religiously committed
      patients in assessing their general level of psychospiritual functioning. 

PMID- 24277126
TI  - Religious self and secular self: Clinical transitions.
AB  - Clerical people, returning to secular life, may undergo shifts in self
      experience, including alterations in internal object relations. Self-psychology,
      positing the importance to health of cohesion of all aspects of self, provides a
      theoretical model for exploring such shifts and their facilitation through
      psychoanalytic psychotherapy. A case of a released Roman Catholic priest is
      discussed to illustrate dynamic processes. Emphasis is on a clinical approach
      that does not require conversion of religious and spiritual self-experience into
      drive derivative formulations. 

PMID- 24277125
TI  - Religion and health relationships: A review.
AB  - This review examines various studies showing the relation between religiosity
      (religious beliefs and/or practices) and health. It also includes church
      attendance and its relation to drug use. The role of the church in health
      promotion is discussed, with examples of church intervention model programs.
      Several attempts have been made to measure religiosity and religious commitment,
      but as yet little has been done to identify specific dimensions of religion as
      they relate to health behaviors. Even though the literature indicates that
      religion is generally associated with health behaviors, health status, and
      longevity, further research on the specifics of this relationship is needed. 

PMID- 24277127
TI  - Initial pastoral visits and communication in depth.
AB  - Pastoral visits undertaken as a way of combining pastoral research on anniversary
      grief with a systematic plan for home visitation became a learning experience for
      the pastor. Three verbatim conversations with church members who donated flowers
      for the communion table during worship are reported. These conversations are
      reflected upon in light of the phenomena of anniversary grief and in terms of D.
      W. Winnicott's theory of communication. 

PMID- 24277128
TI  - Formation of activated biomolecules by condensation on mineral surfaces--a
      comparison of peptide bond formation and phosphate condensation.
AB  - Many studies have reported condensation reactions of prebiotic molecules, such as
      the formation of peptide bonds between amino acids, to occur to some degree on
      mineral surfaces. We have studied several such reactions on the same divided
      silica. When drying steps are applied, the equilibria of peptide formation from
      glycine, and polyphosphate formation from monophosphate, are displaced to the
      right because these reactions are dehydrating condensations, accompanied by the
      emission of water. In contrast, the equilibrium of AMP dismutation is not
      significantly favored by drying. The silica surface plays little role (if any) in
      the thermochemistry of the condensation reactions, but is does play a significant
      kinetic role by acting as a catalyst, lowering the condensation temperatures with
      respect to bulk solids. Of course, the surface also catalyzes the inverse
      hydrolysis reactions. 

PMID- 24277129
TI  - A 23.8-kD alpha-zein with N-terminal sequence and immunological properties
      similar to 26.7-kD alpha-zeins.
AB  - A 23.8-kD alpha-zein polypeptide, K55PC7, has been shown to be a truncated member
      of the 26.7-kD alpha-zein class based on its amino acid composition, N-terminal
      sequence, and immunological properties. This unusual polypeptide was isolated by
      chromatographing whole alpha-zein from inbred K55. The N-terminal sequence of
      K55PC7 is highly homologous to those of 4 putative 26.7-kD alpha-zeins but shows
      no homology to those of 10 putative alpha-zeins that belong to the 23.8-kD class.
      Its higher valine and lower phenylalanine contents also suggest that K55PC7 is a
      member of the 26.7-kD class. In addition, studies with antibodies raised to
      peptides corresponding to regions unique to each of the two alpha-zein classes
      indicate that K55PC7 has immunological similarity to 26.7-kD alpha-zeins. Peptide
      mapping data suggest that K55PC7 is not the putative product of the truncated
      26.7-kD alpha-zein gene zA1 isolated from inbred W64A and described by Spena et
      al. [26]. It appears that K55PC7 occurs as a major component in inbred K55 and is
      a truncated version of a 26.7-kD alpha-zein, arisen either by an internal
      deletion or premature termination due to a nonsense mutation. 

PMID- 24277130
TI  - Blotting Index of Dissimilarity: use to study immunological relatedness of plant
      and animal High Mobility Group (HMG) chromosomal proteins.
AB  - The High Mobility Group (HMG) proteins of vertebrate animals have been the
      subject of intensive study because of evidence that they may be structural
      proteins of transcriptionally active chromatin. Organisms other than vertebrate
      animals have chromatin proteins which meet the operational criteria of salt
      extractability and trichloroacetic acid solubility to be termed HMG proteins.
      However, because the properties of these proteins resemble those of vertebrate
      HMGs to varying degrees and because no definition of "HMG" based on biological
      function is available, a real question exists as to whether the proteins from
      other organisms should be considered HMGs. Because wheat HMG proteins have
      several biochemical properties in common with vertebrate HMGs and yet vary in
      other properties, we have used an immunological approach to study the relatedness
      of these two groups of proteins. We have raised polyclonal antibodies to the
      denatured wheat HMG proteins and have used an immunoblotting procedure to compare
      the affinities of these antibodies to the homologous wheat proteins and to the
      heterologous chicken HMG proteins. We have expressed the immunological
      relatedness of members of these two groups of proteins as the Blotting Index of
      Dissimilarity. This index is intended to be analogous to the Index of
      Dissimilarity determined by microcomplement fixation, and a direct comparison of
      the two procedures results in similar values. The magnitudes of the Blotting
      Indexes of Dissimilarity indicate that the antigenic features of the plant and
      animal HMG proteins have little in common. 

PMID- 24277131
TI  - 5S-rRNA genes in rice embryos.
AB  - The 5S-rRNA from the ungerminated and 48-h-germinated rice embryos differs from
      the wheat, rye and maize by two nucleotides. The 48-h-germinated embryos contain
      another species of 5S-rRNA which differs by 3 nucleotides from the ungerminated
      embryos, thereby showing the expression of two 5S-rRNA genes during germination.
      The 5S-rRNA genes are present in tandem repeats of a 0.3-kb sequence with some
      length heterogeneity in the rice genome. The 5S-rRNA gene that was sequenced is
      identical to that of wheat and maize, except for two nucleotides, C and T, which
      are interchanged at positions 107 and 117. The insert of continuous 5S-rRNA gene
      in pBR322 was transcribed in vitro much more efficiently than the discontinuous
      gene. There was no homology between the 184-bp spacer sequence of 5S-rRNA genes
      in rice and other systems except the presence of the oligo(T) transcription
      terminator sequence. 

PMID- 24277132
TI  - Molecular cloning and nucleotide sequence of the psaA and psaB genes of the
      cyanobacterium Synechococcus sp. PCC 7002.
AB  - The psaA and psaB genes, which encode the P700 chlorophyll a apoproteins of the
      Photosystem I complex, have been cloned from the unicellular, transformable
      cyanobacterium Synechococcus sp. PCC 7002. The nucleotide sequence of these genes
      and of their flanking sequences have been determined by the chain termination
      method. As found in the chloroplast genomes of higher plants, the psaA gene lies
      5' to the psaB gene; however, the cyanobacterial genes are separated by a greater
      distance (173 vs. 25-26 bp). The psaA gene is predicted to encode a polypeptide
      of 739 amino acid residues (81.7 kDa), and the psaB gene is predicted to encode a
      polypeptide of 733 residues (81.4 kDa). The cyanobacterial psa gene products are
      76% to 81% identical to their higher plant homologues; moreover, because of
      conservative amino acid replacements, the cyanobacterial sequences are more than
      95% homologous to those determined for higher plants. These results provide the
      basis for a genetic analysis of Photosystem I, and are discussed in relationship
      to structural and functional aspects of the Photosystem I complexes of both
      cyanobacteria and higher plants. 

PMID- 24277133
TI  - Plant gene expression in effective and ineffective root nodules of alfalfa
      (Medicago sativa).
AB  - Expression of plant genes involved in the symbiosis between alfalfa (Medicago
      sativa) and Rhizobium meliloti has been studied by comparing root and root nodule
      mRNA populations. Two-dimensional gel electrophoretic separation of the in vitro
      translation products of polyA(+) RNA isolated from either roots or effective root
      nodules has allowed us to identify thirteen nodule-specific translation products,
      including those corresponding to the leghemoglobins (Lb). These translation
      products, representing putative nodulin mRNAs, are first detected between 9 and
      12 days after inoculation, a result which has been confirmed for Lb mRNA by
      Northern blotting and hybridization with a Lb cDNA probe. Analysis of three
      different types of ineffective root nodules arrested in different stages of
      development has led to the following conclusions. (i) The transcription of eleven
      nodule-specific genes, including the Lb genes, is independent of nitrogen-fixing
      activity. (ii) Differentiation of the primary nodule structure does not require
      the transcription of any of these genes but can be correlated with a dramatic
      reduction in the level of at least five transcripts present in the root. (iii)
      There is enhanced expression of certain plant genes in the case of nodules
      elicited by an Agrobacterium strain carrying the symbiotic plasmid of R.
      meliloti. 

PMID- 24277134
TI  - The central part of the cyanelle rDNA unit of Cyanophora paradoxa: Sequence
      comparison with chloroplasts and cyanobacteria.
AB  - The 287-bp spacer and the flanking 3'-end of the 16S- and 5'-end of the 23S-rRNA
      genes of the cyanelles from Cyanophora paradoxa have been sequenced and compared
      with the corresponding regions of cyanobacteria and chloroplasts. The spacer
      contains the uninterrupted genes for tRNA(ile) and tRNA(ala). All coding regions
      show high homology to their prokaryotic counterparts. At the 3'-end of the 16S
      rDNA a CCTCCTTT sequence has been identified which is complementary to putative
      ribosome binding sites observed immediately upstream of the coding region of
      cyanelle protein genes. 

PMID- 24277135
TI  - Physical map and gene localization on sunflower (Helianthus annuus) chloroplast
      DNA: evidence for an inversion of a 23.5-kbp segment in the large single copy
      region.
AB  - As a first step in the study of chloroplast genome variability in the genus
      Helianthus, a physical restriction map of sunflower (Helianthus annuus)
      chloroplast DNA (cpDNA) has been constructed using restriction endonucleases BamH
      I, Hind III, Pst I, Pvu II and Sac. I. Sunflower circular DNA contains an
      inverted repeat structure with the two copies (23 kbp each) separated by a large
      (86 kbp) and a small (20 kbp) single copy region. Its total length is therefore
      about 152 kbp. Sunflower cpDNA is essentially colinear with that of tobacco with
      the exception of an inversion of a 23.5-kbp segment in the large single copy
      region. Gene localization on the sunflower cpDNA and comparison of the gene map
      with that from tobacco chloroplasts have revealed that the endpoints of the
      inversion are located between the trnT and trnE genes on the one hand, and
      between the trnG and trnS genes on the other hand.Analysis of BamH I restriction
      fragment patterns of H. annuus, H. occidentalis ssp. plantagineus, H.
      grossesseratus, H. decapetalus, H. giganteus, H. maximiliani and H. tuberosus
      cpDNAs suggests that structural variations are present in the genus Helianthus. 

PMID- 24277136
TI  - The pea lectin gene family contains only one functional gene.
AB  - Molecular hybridization experiments have shown that the pea genome contains four
      regions which hybridize with pea lectin cDNA (Kaminski, Buffard, and Strosberg,
      1986. Plant Science 46, 111-116). The complete organization of the pea lectin
      gene family was investigated. Four partial EcoRI genomic libraries were screened
      with a lectin cDNA (pPS 15-50) covering the entire coding region. Four positive
      recombinant phages, lambdaI 101, lambdaI 52, lambdaIII 51 and lambdaIV 22, were
      isolated and the DNA sequences of the subclones, designated respectively PSL1,
      PSL2, PSL3 and PSL4, were determined. PSL2, PSL3 and PSL4 are incomplete genes;
      the presence of several stop codons in the correct reading frames indicate that
      these genes cannot code for a functional lectin protein. The sequences of PSL1
      and pPS 15-50 have identical coding regions. The pea lectin gene has no
      intervening sequences and is flanked at its 5' region by a sequence containing an
      exceptionally high A+T content (73%). Eucaryotic consensus sequences such as a
      TATA box and a polyadenylation signal are also found in the flanking regions of
      the PSL1 clone. 

PMID- 24277137
TI  - Ribosomal RNA genes in plants: variability in copy number and in the intergenic
      spacer.
AB  - Ribosomal RNA genes in plants are highly variable both in copy number and in
      intergenic spacer (IGS) length. This variability exists not only between
      distantly related species, but among members of the same genus and also among
      members of the same population of a single species. Analysis of inheritance
      indicates that copy number change is rapid, occurring even among somatic cells of
      individual plants, and that up to 90% or more of the gene copies are superfluous.
      Subrepetitive sequences within the IGS appear to be changing rapidly as well.
      They are not only variable in sequence from one species to the next, but can vary
      in number between neighboring gene repeats on the chromosome. In all species
      examined in detail they are located in the same region of the IGS and contain
      sequences that can be folded into stem-loop structures flanked by a pyrimidine
      rich region. It has been suggested that these subrepeats function in
      transcriptional enhancement, termination or processing, or in recombination
      events generating the high multiplicity of ribosomal genes. 

PMID- 24277138
TI  - Introduction.

PMID- 24277139
TI  - Chirality in insect communication.
AB  - In dealing with chiral molecules, the natural-products chemist must be
      knowledgeable in several areas of stereochemistry. This brief survey will serve
      for simple situations and as a source of references for more complex molecules. 

PMID- 24277140
TI  - Olfactory coding in the perception of semiochemicals.
AB  - Information processing in the olfactory pathway underlying the perception of
      semiochemicals by insects is discussed. Both the chemical message for mates and
      the message for food consist of blends of chemicals. Olfactory receptors in an
      insect species are tuned to the detection of those compounds which comprise such
      chemical messages for that species. The classification of receptors as
      specialists or generalists coincides with two concepts of information processing,
      i.e., labeled lines and across-fiber patterns, respectively. The olfactory code
      coming from antennal receptors inPieris brassicae larvae is a combination of
      labeled lines and across-fiber patterning. When antennae of adult Colorado potato
      beetles,Leptinotarsa decemlineata, are stimulated by binary mixtures of leaf odor
      components, the pattern of neural activities in the olfactory receptors shows
      some separation into two channels, quantitative versus qualitative detection. The
      separation is complete in the antennal lobe of this beetle. 

PMID- 24277141
TI  - Pheromone biosynthesis in lepidoptera.
AB  - Pheromone components for many lepidopteran species are produced by the use of
      unique chain-shortening and Delta9, Delta10, and Delta11 desaturase systems.
      Correlations in the Tortricidae indicate that the pheromone components derived
      from Delta9 and Delta01 desaturases are found in the more primitive species
      (those possessing morphological plesiomorphies). The precise blend ofZ andE
      acetates in a number of species is regulated in the final reduction sequence from
      acyl intermediates. Preliminary research has been conducted on the
      characterization of the various desaturase enzymes used and on the important
      blend regulating sequence. Initial purification work on the Delta11 desaturase
      enzyme found in the cabbage looper moth is reported. 

PMID- 24277142
TI  - Chemical studies of proteins that degrade pheromones : Cyclopropanated,
      fluorinated, and electrophilic analogs of unsaturated aldehyde pheromones.
AB  - Aldehyde components of lepidopterous pheromones are converted to carboxylic acids
      by aldehyde oxidizing enzymes (AOEs) that are present at high levels in antennal
      tissues of adult moths. The AOEs may include O2-requiring aldehyde oxidases as
      well as nucleotide-cofactor-requiring aldehyde dehydrogenases. Three classes of
      inhibitors were synthesized and examined in vitro for AOE inhibition
      usingHeliothis virescens antennae: (1) cyclopropanols, (2) alpha-fluorinated
      aldehydes, and (3) alpha,beta-unsaturated carbonyls. First, cyclopropanated
      analogs of (Z)-11-hexadecenal (Z11-16?A1), a common unsaturated aldehyde
      component of many species' pheromone blends, were synthesized as isosteric
      pheromone analogs and as potential inhibitors of the moth AOEs. NMR assignments
      are reported for thecis- andtrans-cyclopropanols. Cyclopropanols appear to act as
      oxidase-activated AOE inhibitors, perhaps via the unstable cyclopropanones.
      Second, alpha-fluoro and alpha,alpha-difluoro substituted analogs ofZ9-14?A1 were
      synthesized and shown to be modest inhibitors of both the alcohol oxidase and AOE
      activities. Finally, the most potent inhibitors were alpha,beta-unsaturated
      carbonyl mimics of theZ11-16?A1. The alpha-methylene aldehyde was 1000-fold less
      effective than the vinyl ketoneZ1,11-16?3-oxo. This inhibition appears
      irreversible and is postulated to involve electrophilic modification of an active
      site sulfur nucleophile. 

PMID- 24277143
TI  - Genetic regulation of sex pheromone production and response : Interaction of
      sympatric pheromonal types of European corn borer,Ostrinia nubilalis
      (Lepidoptera: Pyralidae).
AB  - The sex pheromone communication system of the European corn borer moth varies
      intraspecifically. Analyses of pheromonal extracts of wild females, collected in
      a region where the types (each producing a different isomeric proportion ofZ-
      andE-11-tetradecenyl acetate) are sympatric, showed that theZ pheromone
      production allele frequency was ca. 4 times greater than theE allele. The paucity
      ofE production and response alleles in the population indicates that moths
      inheriting those alleles concomitantly inherit some undefined disadvantage. The
      types interbreed, but the frequency of heterozygous pheromone-production types
      among wild females was less than predicted by Hardy-Weinberg equilibrium and was
      evidence of positive assortative mating. Rates of male captures in field traps
      baited with females of the three pheromonal types also evidenced assortative
      mating in the population. Progeny tests with males captured in the traps provided
      circumstantial evidence that pheromone response and production functions in the
      species are regulated by separate genetic loci and that the loci are not always
      complementary; i.e., a male can carry an allele coding for production of one
      pheromonal isomer ratio but can be genetically predisposed to respond to another.

PMID- 24277144
TI  - Selected factors influencing neurohormonal regulation of sex pheromone production
      inHeliothis species.
AB  - Sex pheromone production and release in females ofHeliothis species exhibit a
      diel periodicity. Phermone production is controlled by a hormone, the pheromone
      biosynthesis activating neuropeptide (PBAN). Release of PBAN to activate
      pheromone production follows a circadian rhythm. InH. zea females, mating
      terminates pheromone production. An unidentified hemolymph-borne factor is
      transferred from the male to the female during mating. It is speculated that this
      factor interacts with the release mechanism of PBAN to prevent further production
      of the pheromone following mating. Wild females ofH. phloxiphaga (reared from
      larvae collected in the field) did not produce or release the sex pheromone
      unless kept in association with the host plant. Pheromone production could be
      induced in these females by the injection of PBAN. It is suggested that a signal
      from the host plant is essential to trigger the release of PBAN to induce
      pheromone production. 

PMID- 24277145
TI  - Chemical communication in cucujid grain beetles.
AB  - Males of five sympatric species of economically damaging cucujid grain
      beetles,Cryptolestes ferrugineus (Stephens),C. pusillus (Schonhen),C. turcicus
      (Grouvelle),Oryzaephilus mercator (Fauvel), andO. surinamensis (L.), produce
      macrolide aggregation pheromones especially in the presence of food. Work leading
      to the isolation, identification, and establishment of biological activity of
      these semiochemicals is reviewed. The trivial name "cucujolide" is proposed and
      used to identify these compounds that are characteristic of the Cucujidae. The
      twoOryzaephilus share species share a common cucujolide pheromone,
      whileCryptolestes species use cucujolides that are either enantiomeric, unique to
      the genus, or released in trace quantities byOryzaephilus spp. and not used as
      pheromones by the latter species. The major mechanisms for species specificity in
      chemical communication are: (1) presence of a unique pheromone (C. ferrugineus
      andC. pusillus); (2) use of pheromones that are inactive alone but synergize
      response to cucujolides unique to a species (C. pusillus, C. turcicus, andO.
      surinamensis); (3) response to only one enantiomer of a pheromone (C.
      ferrugineus, O. surinamensis, andO. mercator); and (4) synergism between
      enantiomers of a pheromone (C. turcicus). The only species for which cross
      attraction was evident wasO. mercator toO. surinamensis. Both sexes
      ofOryzaephilus spp. produce (R)-1-octen-3-ol, which highly synergizes response to
      the cucujolide pheromones. Similar synergism occurs between hexanal, octanal, and
      nonanal and the cucujolide pheromones ofOryzaephilus spp. The males of a sixth
      cucujid species,Cathartus quadricollis (Guer) produce a different aggregation
      pheromone, (3R,6E)-7-methyl-6-nonen-3-yl acetate. Trapping ofCryptolestes
      andOryzaephilus spp. in cardboard traps baited with pheromones is efficient in
      environments mimicking food-storage areas. Pheromone-baited plastic probe traps
      are the most efficient at capturing these species in infested grain. 

PMID- 24277146
TI  - Eclectic chemisociality of the honeybee : A wealth of behaviors, pheromones, and
      exocrine glands.
AB  - A dazzling variety of honeybee behaviors are triggered by pheromones produced by
      disparate exocrine glands. A multiplicity of chemical releasers of social
      behavior has been demonstrated to regulate a diversity of societal interactions,
      and many of these compounds are synthesized with great caste specificity. Recent
      investigations have resulted in the identification of a host of new compounds
      that are products of either worker or queen honeybees. This report fractionates
      these newly identified exocrine products according to their glandular
      proveniences and focuses on both the structural and behavioral eclecticism that
      characterizes these chemical signaling agents. 

PMID- 24277147
TI  - Contemporary frontiers in insect semiochemical research.
AB  - Recent advances in analytical chemistry coupled with more definitive behavioral
      analyses have allowed more rigorous identification of many insect pheromones.
      This, in turn, has increased our understanding of the roles of pheromones in
      mediating insect behavior. Other semiochemicals that mediate insect behavior
      include those that enable parasitic and predatory insects to locate their hosts
      or prey. These may be produced by the host insects or by the plant on which they
      feed. Additionally, there are pheromones and plant-produced seminochemicals that
      regulate insect oviposition, a critical phase in the life cycle of insects. The
      challenge to chemists and biologists is to explore these areas to find new
      environmentally safe methods to control insect pests. One of the newer strategies
      used to investigate these semiochemicals is the study of the biochemistry of
      pheromone production and semiochemical perception in insects. These types of
      studies may reveal weak links in these systems that can be exploited to develop
      new, more effective and environmentally safe control methods. 

PMID- 24277148
TI  - Properties of cuticular oxidases used for sex pheromone biosynthesis byHeliothis
      zea.
AB  - Biosynthesis of the aldehydic sex pheromone components released by females
      ofHeliothis zea was found to be catalyzed by primary alcohol oxidases residing in
      the cuticle that covers the glands. Activity, as indicated by conversion of
      primary alcohol to aldehyde, was as high in cell-free cuticle as it was in intact
      pheromone glands. Studies indicated that some activity was associated with the
      surface of the epicuticle and could be removed, into buffer, by sonication.
      However, the majority of activity lies within the inner epicuticle and exo- and
      endocuticular layers. The oxidase was not functional in pharate pupae that did
      not have mature adult cuticle but became functional just prior to adult
      emergence. The enzyme in individual glands was saturated at alcohol
      concentrations above 100 n. moles. Nonionic detergents did not affect the
      activity of the oxidase in the cuticle but treatment with either 7 M urea or 1%
      SDS resulted in total loss of activity. Studies on the effect of pH indicated an
      optimum at 6.4; however, activity was high throughout the range of 5-9. The
      oxidase was functional in both dichloromethane and hexane, suggesting that this
      enzyme system may have applications for organic synthesis of aldehydes. 

PMID- 24277149
TI  - NHS agency takes out private prosecution against mentally ill patient who hit
      healthcare assistant.

PMID- 24277150
TI  - Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma
      rejection.
AB  - Glioblastomas (GBs) are the most aggressive form of primary brain cancer and
      virtually incurable. Accumulation of regulatory T (T reg) cells in GBs is thought
      to contribute to the dampening of antitumor immunity. Using a syngeneic mouse
      model for GB, we tested whether local delivery of cytokines could render the
      immunosuppressive GB microenvironment conducive to an antitumor immune response.
      IL-12 but not IL-23 reversed GB-induced immunosuppression and led to tumor
      clearance. In contrast to models of skin or lung cancer, IL-12-mediated glioma
      rejection was T cell dependent and elicited potent immunological memory. To
      translate these findings into a clinically relevant setting, we allowed for GB
      progression before initiating therapy. Combined intratumoral IL-12 application
      with systemic blockade of the co-inhibitory receptor CTLA-4 on T cells led to
      tumor eradication even at advanced disease stages where monotherapy with either
      IL-12 or CTLA-4 blockade failed. The combination of IL-12 and CTLA-4 blockade
      acts predominantly on CD4(+) cells, causing a drastic decrease in FoxP3(+) T reg
      cells and an increase in effector T (T eff) cells. Our data provide compelling
      preclinical findings warranting swift translation into clinical trials in GB and
      represent a promising approach to increase response rates of CTLA-4 blockade in
      solid tumors. 

PMID- 24277151
TI  - Nfil3-independent lineage maintenance and antiviral response of natural killer
      cells.
AB  - Development of the natural killer (NK) cell lineage is dependent on the
      transcription factor Nfil3 (or E4BP4), which is thought to act downstream of IL
      15 signaling. Nfil3-deficient mice lack NK cells, whereas other lymphocyte
      lineages (B, T, and NKT cells) remain largely intact. We report the appearance of
      Ly49H-expressing NK cells in Nfil3(-/-) mice infected with mouse cytomegalovirus
      (MCMV) or recombinant viruses expressing the viral m157 glycoprotein. Nfil3(-/-)
      NK cells at the peak of antigen-driven expansion were functionally similar to NK
      cells from infected wild-type mice with respect to IFN-gamma production and
      cytotoxicity, and could comparably produce long-lived memory NK cells that
      persisted in lymphoid and nonlymphoid tissues for >60 d. We demonstrate that
      generation and maintenance of NK cell memory is an Nfil3-independent but IL-15
      dependent process. Furthermore, specific ablation of Nfil3 in either immature NK
      cells in the bone marrow or mature peripheral NK cells had no observable effect
      on NK cell lineage maintenance or homeostasis. Thus, expression of Nfil3 is
      crucial only early in the development of NK cells, and signals through activating
      receptors and proinflammatory cytokines during viral infection can bypass the
      requirement for Nfil3, promoting the proliferation and long-term survival of
      virus-specific NK cells. 

PMID- 24277152
TI  - Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission.
AB  - The neutralizing activity of anti-HIV-1 antibodies is typically measured in
      assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to
      cell transmission is a major mechanism of viral spread, and the effect of the
      recently described broadly neutralizing antibodies (bNAbs) on this mode of
      transmission remains unknown. Here we identify a subset of bNAbs that inhibit
      both cell-free and cell-mediated infection in primary CD4(+) lymphocytes. These
      antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the
      glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations
      by inhibiting multiple steps of viral cell to cell transmission. These antibodies
      accumulate at virological synapses and impair the clustering and fusion of
      infected and target cells and the transfer of viral material to uninfected T
      cells. In addition, they block viral cell to cell transmission to plasmacytoid
      DCs and thereby interfere with type-I IFN production. Thus, only a subset of
      bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property
      should be considered an important characteristic defining antibody potency for
      therapeutic or prophylactic antiviral strategies. 

PMID- 24277154
TI  - Urodynamic improvements following oral medical therapy for partial bladder outlet
      obstruction in an animal model.
AB  - PURPOSE: Bladder deterioration after partial outlet obstruction (pBOO) occurs
      commonly and has significant clinical implications. Our previous animal model
      results described the progression of pBOO to hypertrophy and fibrosis. We wished
      to determine if the pathologic process of pBOO can be altered with rationally
      chosen oral medications. MATERIALS AND METHODS: Female Sprague-Dawley rats
      underwent controlled surgically induced pBOO. Rats were maintained for a period
      of 16 weeks at which point urodynamics were performed, and organs harvested. Rats
      were divided into four groups, each receiving different daily treatment: control
      (saline), oxybutynin (3 mg/kg), rapamycin (2 mg/kg), and tadalafil (2 mg/kg).
      Outcomes were assessed after 4,8,12, or 16 weeks. Measures included animal
      health, urodynamics, histology, mass spectrometry for collagen content, and rtPCR
      for inflammatory mediators. RESULTS: Rapamycin treated animals exhibited
      significant mortality at later time points. Oxybutinin and tadalafil treated
      bladders demonstrated significant improvements in bladder capacity and
      compliance, with less detrusor hypertrophy than controls. Tadalafil also resulted
      in a significant down-regulation of HIF-1alpha, while decorin, biglycan, and TGF
      beta were upregulated in treated animals. Tadalafil treated bladders measured
      lower collagen content towards the end of the study, indicating an antifibrotic
      effect. CONCLUSIONS: Our study has effectively demonstrated that deleterious
      changes secondary to pBOO can be altered pharmacologically. Oxybutinin and
      tadalafil seem to have a time-dependent protective effect on the detrusor muscle,
      although with different mechanisms of action. Tadalafil treatment in this setting
      appears to have an antifibrotic effect. This work has the potential to seed
      important clinical studies and improve clinical practice.

PMID- 24277153
TI  - RNA recognition by human TLR8 can lead to autoimmune inflammation.
AB  - Studies on the role of the RNA receptor TLR8 in inflammation have been limited by
      its different function in human versus rodents. We have generated multiple lines
      of transgenic mice expressing different levels of human TLR8. The high copy
      number chimeras were unable to pass germline; developed severe inflammation
      targeting the pancreas, salivary glands, and joints; and the severity of the
      specific phenotypes closely correlated with the huTLR8 expression levels. Mice
      with relatively low expression levels survived and bred successfully but had
      increased susceptibility to collagen-induced arthritis, and the levels of huTLR8
      correlated with proinflammatory cytokines in the joints of the animals. At the
      cellular level, huTLR8 signaling exerted a DC-intrinsic effect leading to up
      regulation of co-stimulatory molecules and subsequent T cell activation. A
      pathogenic role for TLR8 in human diseases was suggested by its increased
      expression in patients with systemic arthritis and the correlation of TLR8
      expression with the elevation of IL-1beta levels and disease status. We found
      that the consequence of self-recognition via TLR8 results in a constellation of
      diseases, strikingly distinct from those related to TLR7 signaling, and points to
      specific inflammatory diseases that may benefit from inhibition of TLR8 in
      humans. 

PMID- 24277155
TI  - The effect of a hypoglycemia treatment protocol on glycemic variability in
      critically ill patients.
AB  - INTRODUCTION: Hypoglycemia and glucose variability are independently associated
      with increased mortality in septic, surgical, and mixed intensive care unit (ICU)
      patients. Treatment of hypoglycemia with dextrose 50% can overcorrect blood
      glucose levels and increase glucose variability. The purpose of this study is to
      evaluate the effect of a hypoglycemia treatment protocol focused on minimizing
      glucose variability in critically ill patients. METHODS: This retrospective
      analysis was conducted at a 772-bed community teaching hospital in Detroit,
      Michigan. A standardized nursing-driven hypoglycemia treatment protocol specific
      to critically ill patients was implemented. Glucose variability, amount of
      dextrose administered, subsequent glucose monitoring, hypoglycemia recurrence,
      and mortality were compared between pre- and postprotocol groups. RESULTS: The
      coefficient of variability of blood glucose in the postprotocol group (n = 53)
      was decreased compared with the preprotocol group (n = 52), 40.9% versus 49.3%,
      respectively (P = .048). Dextrose usage was significantly reduced between groups
      (21.2 g preprotocol vs 11.5 g postprotocol; P < .001). The time to first blood
      glucose check was 36 minutes after protocol implementation compared to 61 minutes
      before the protocol (P = .003). Finally, the incidence of continued hypoglycemia
      following dextrose administration and ICU mortality was similar between groups.
      CONCLUSIONS: Implementation of the hypoglycemia treatment protocol described led
      to a reduction in glucose variability, while still providing a safe and effective
      way to manage hypoglycemia in critically ill patients.

PMID- 24277156
TI  - Role of nuclear receptor on regulation of BDNF and neuroinflammation in
      hippocampus of beta-amyloid animal model of Alzheimer's disease.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been
      reported to provide neuroprotective effects against neurodegenerative diseases.
      The current study was carried out to investigate the effects of chronic
      administration of pioglitazone, a PPAR-gamma agonist, on cognitive impairment in
      an animal model of Alzheimer's disease induced by beta-amyloid. Wistar rats
      received intracerebroventricular (ICV) beta-amyloid (betaA) application (3 nmol/3
      MUL), and behavioral alterations (locomotor activity and memory performance) were
      assessed. Animals were sacrificed immediately following the last behavioral
      session, and their brains were removed and dissected. Mitochondrial enzymes,
      oxidative parameters, inflammatory mediators (TNF-alpha, IL-6), caspase activity,
      and BDNF levels were measured in the hippocampus. ICV betaA-treated rats showed a
      memory deficit and significantly decreased BDNF level, simultaneously, increase
      in mitochondrial oxidative damage and inflammatory mediators in the hippocampus.
      Memory impairment and oxidative damage were reversed by administration of
      pioglitazone (15 and 30 mg/kg). Pioglitazone also significantly restored the BDNF
      level and attenuated the actions of inflammatory markers in ICV betaA-treated
      rats. However, pretreatment with PPAR-gamma antagonist BADGE (15 mg/kg) with
      higher dose of pioglitazone significantly reversed its protective action in
      memory impairment in betaA-treated rats, which indicates the involvement of PPAR
      gamma receptors mediating neuroprotective action. These results demonstrate that
      pioglitazone offers protection against beta-amyloid-induced memory dysfunction
      possibly due to its antioxidant, anti-inflammatory, anti-apoptotic action and
      neurogenesis-like effect therefore, could have a therapeutic potential in
      Alzheimer's disease.

PMID- 24277157
TI  - 17beta-estradiol delays 6-OHDA-induced apoptosis by acting on Nur77 translocation
      from the nucleus to the cytoplasm.
AB  - Nuclear receptors (Nurs) represent a large family of gene expression regulating
      proteins. Gathering evidence indicates an important role for Nurs as
      transcription factors in dopamine neurotransmission. Nur77, a member of the Nur
      superfamily, plays a role in mediating the effects of antiparkinsonian and
      neuroleptic drugs. Besides, Nur77 survival and apoptotic roles depend largely on
      its subcellular localization. Estrogens are known for their neuroprotective
      properties, as demonstrated in animal and clinical studies. However, their action
      on Nur77 translocation pertaining to neuroprotection has not been investigated
      yet. The aim of our study was to perform a kinetic study on the effect of
      neurotoxic 6-hydroxydopamine (6-OHDA) and 17beta-estradiol (E2) on the
      subcellular localization of Nur77 with reference to the modulation of apoptosis
      in PC12 cells. Our results demonstrate that E2 administration alone does not
      affect Nur77 cytoplasmic/nuclear ratio, mRNA levels, or apoptosis in PC12 cells.
      The neurotoxin 6-OHDA significantly enhances cytoplasmic localization of Nur77
      after merely 3 h, while precipitating apoptosis. 6-OHDA also increases Nur77
      transcription, which could partly explain the rise in cytoplasmic localization of
      the protein. Finally, treatment with both E2 and 6-OHDA delays Nur77 accumulation
      in the cytoplasm and delays cell death for a few hours in our cellular paradigm.
      Pre-treatment with E2 does not alter the increase in levels of Nur77 mRNA
      produced by 6-OHDA, suggesting that a raise in nuclear translocation is likely
      responsible for the stabilization of the cytoplasmic/nuclear ratio until 6 h.
      These results suggest an intriguing cooperation between E2 and Nur77 toward
      cellular fate guidance. 

PMID- 24277159
TI  - (S)-ZJM-289 preconditioning induces a late phase protection against nervous
      injury induced by transient cerebral ischemia and oxygen-glucose deprivation.
AB  - (S)-ZJM-289, a novel nitric oxide (NO)-releasing derivative of 3-n
      butylphthalide, induces the neuroprotection in a rat model of focal cerebral
      ischemia/reperfusion (I/R). However, much is unknown about the late phase effect
      in the neuroprotection of (S)-ZJM-289 preconditioning. The purpose of this study
      is to explore the late phase neuroprotection of (S)-ZJM-289 preconditioning, as
      well as underlying mechanisms involved. Preconditioning with 40-160 mg/kg, (S)
      ZJM-289 significantly reduces brain damage after I/R. (S)-ZJM-289 preconditioning
      is effective when applied 1-3 days before I/R. Moreover, the degrees of
      neuroprotection offered by (S)-ZJM-289 preconditioning and ischemic
      preconditioning are virtually identical. (S)-ZJM-289 preconditioning also
      protects primary cultured cortical neurons against oxygen-glucose deprivation and
      recovery-induced cytotoxicity in vitro. (S)-ZJM-289 preconditioning significantly
      increases the generation of NO, but has no effect on the nitric oxide synthase
      activities. Additionally, (S)-ZJM-289 preconditioning promotes the dissociation
      between nuclear-factor-E2-related factor (Nrf2) and kelch-like ECH-associated
      protein 1, and induces Nrf2 nuclear localization. The neuroprotection of (S)-ZJM
      289 preconditioning is blocked by Nrf2-siRNA in vitro. (S)-ZJM-289
      preconditioning up-regulates antioxidant enzymes against nervous injury. (S)-ZJM
      289 preconditioning significantly activates extracellular regulated protein
      kinases (ERK) and inhibits c-Jun N-terminal kinases signaling cascade. The
      neuroprotection is abolished by the ERK inhibitor PD98059 in vitro. Subsequently,
      (S)-ZJM-289 preconditioning increases the levels of anti-apoptotic protein B cell
      lymphoma 2 (Bcl-2) and inhibited the translocation of Bcl-2 associated X to the
      mitochondria, thus attenuating the release of cytochrome c from the mitochondria
      and the activation of downstream caspase. These results suggest that (S)-ZJM-289
      preconditioning exerts the late phase protection against nervous injury induced
      by transient cerebral ischemia and oxygen-glucose deprivation.

PMID- 24277160
TI  - Multidisciplinary management strategies for acute non-variceal upper
      gastrointestinal bleeding.
AB  - BACKGROUND: The modern management of acute non-variceal upper gastrointestinal
      bleeding is centred on endoscopy, with recourse to interventional radiology and
      surgery in refractory cases. The appropriate use of intervention to optimize
      outcomes is reviewed. METHODS: A literature search was undertaken of PubMed and
      the Cochrane Central Register of Controlled Trials between January 1990 and April
      2013 using validated search terms (with restrictions) relevant to upper
      gastrointestinal bleeding. RESULTS: Appropriate and adequate resuscitation, and
      risk stratification using validated scores should be initiated at diagnosis.
      Coagulopathy should be corrected along with blood transfusions, aiming for an
      international normalized ratio of less than 2.5 to proceed with possible
      endoscopic haemostasis and a haemoglobin level of 70 g/l (excluding patients with
      severe bleeding or ischaemia). Prokinetics and proton pump inhibitors (PPIs) can
      be administered while awaiting endoscopy, although they do not affect rebleeding,
      surgery or mortality rates. Endoscopic haemostasis using thermal or mechanical
      therapies alone or in combination with injection should be used in all patients
      with high-risk stigmata (Forrest I-IIb) within 24 h of presentation (possibly
      within 12 h if there is severe bleeding), followed by a 72-h intravenous infusion
      of PPI that has been shown to decrease further rebleeding, surgery and mortality.
      A second attempt at endoscopic haemostasis is generally made in patients with
      rebleeding. Uncontrolled bleeding should be treated with targeted or empirical
      transcatheter arterial embolization. Surgical intervention is required in the
      event of failure of endoscopic and radiological measures. Secondary PPI
      prophylaxis when indicated and Helicobacter pylori eradication are necessary to
      decrease recurrent bleeding, keeping in mind the increased false-negative testing
      rates in the setting of acute bleeding. CONCLUSION: An evidence-based approach
      with multidisciplinary collaboration is required to optimize outcomes of patients
      presenting with acute non-variceal upper gastrointestinal bleeding.

PMID- 24277161
TI  - Cognitive behavior therapy for hoarding disorder: follow-up findings and
      predictors of outcome.
AB  - BACKGROUND: A cognitive-behavioral model of hoarding posits deficits in
      information processing, maladaptive beliefs about and attachments to possessions
      that provoke distress and avoidance, and positive emotional responses to saving
      and acquiring that reinforce these behaviors. A 26-session individual cognitive
      behavioral therapy (CBT) based on this model showed significant reductions in
      hoarding symptoms and large effect sizes (Steketee et al.([1])). METHODS: The
      present study presents findings at follow-up (up to 12 months), as well as
      predictors of outcome at posttreatment (n = 37) and follow-up (n = 31). RESULTS:
      Significant improvements at post-treatment were sustained at follow-up with large
      effects, and Clinical Global Impression-Improvement (CGI-I) ratings by clinicians
      and patients at follow-up indicated that 62 and 79% of patients were rated "much
      improved" or "very much improved," respectively. The most prevalent patterns of
      outcome were improvement followed by stable gains or little improvement across
      all time points. Pretreatment severity of hoarding, overall clinical status,
      gender, perfectionism, and social anxiety were all associated with worse outcome.
      Only perfectionism and gender emerged as significant predictors after controlling
      for initial hoarding severity. CONCLUSIONS: The present findings suggest general
      stability of individual CBT outcomes for hoarding and indicated that gender,
      perfectionism, and social anxiety may affect outcomes. More research on larger
      samples is needed to direct efforts to improve treatment for hoarding.

PMID- 24277158
TI  - Cisplatin inhibits hippocampal cell proliferation and alters the expression of
      apoptotic genes.
AB  - The hippocampus, which is critical for memory and spatial navigation, contains a
      proliferating stem cell niche that is especially vulnerable to antineoplastic
      drugs such as cisplatin. Although the damaging effects of cisplatin have recently
      been recognized, the molecular mechanisms underlying its toxic effects on this
      vital region are largely unknown. Using a focused apoptosis gene array, we
      analyzed the early cisplatin-induced changes in gene expression in the
      hippocampus of adult Sprague-Dawley rats and compared the results to those from
      the inferior colliculus, a non-mitotic auditory region resistant to cisplatin
      induced cell death. Two days after a 12 mg/kg dose of cisplatin, significant
      increases were observed in five proapoptotic genes: Bik, Bid, Bok, Trp53p2, and
      Card6 and a significant decrease in one antiapoptotic gene Bcl2a1. In contrast,
      Nol3, an antiapoptotic gene, showed a significant increase in expression. The
      cisplatin-induced increase in Bid mRNA and decrease in Bcl2a1 mRNA were
      accompanied by a corresponding increase and decrease of their respective proteins
      in the hippocampus. In contrast, the cisplatin-induced changes in Bcl2a1, Bid,
      Bik, and Bok gene expression in the inferior colliculus were strikingly different
      from those in the hippocampus consistent with the greater susceptibility of the
      hippocampus to cisplatin toxicity. Cisplatin also significantly reduced
      immunolabeling of the cell proliferation marker Ki67 in the subgranular zone of
      the hippocampus 2 days post-treatment. These results indicate that cisplatin
      induced hippocampal cell death is mediated by increased expression of
      proapoptotic and decreased antiapoptotic genes and proteins that likely inhibit
      hippocampal cell proliferation.

PMID- 24277162
TI  - Acquisition of a visual discrimination and reversal learning task by Labrador
      retrievers.
AB  - Optimal cognitive ability is likely important for military working dogs (MWD)
      trained to detect explosives. An assessment of a dog's ability to rapidly learn
      discriminations might be useful in the MWD selection process. In this study,
      visual discrimination and reversal tasks were used to assess cognitive
      performance in Labrador retrievers selected for an explosives detection program
      using a modified version of the Toronto General Testing Apparatus (TGTA), a
      system developed for assessing performance in a battery of neuropsychological
      tests in canines. The results of the current study revealed that, as previously
      found with beagles tested using the TGTA, Labrador retrievers (N = 16) readily
      acquired both tasks and learned the discrimination task significantly faster than
      the reversal task. The present study confirmed that the modified TGTA system is
      suitable for cognitive evaluations in Labrador retriever MWDs and can be used to
      further explore effects of sex, phenotype, age, and other factors in relation to
      canine cognition and learning, and may provide an additional screening tool for
      MWD selection.

PMID- 24277164
TI  - Implications of reiterative DNA-Metal ion complexes in the induction and
      development of neoplastic cells.
AB  - Experimental data on the content in metal ions of DNA preparations from various
      neoplastic and healthy tissues are summarized: metal ions are preferentially
      bound to reiterative DNA sequences, where they may induce conformational
      variations and thus modify the binding of effector molecules such as repressors
      and polymerases.A model is described where essential and toxic metals are
      successively loaded on ligand acceptor groups of increasing affinity and thus may
      reach the final active sites: enzymes and reiterative DNA sequences (equated at
      least partially to regulative DNA sequences). The effects of some molecules,
      including peptides, antibiotics, growth factors, hormones, and antineoplastic
      substances, on DNA conformation could be explained in part by their chelating
      ability.The neoplastic state may be induced by a modification of metal ion
      transfer chains: quantitatively by a continuous derepression of genes coding for
      metal ligands, genes that are only temporarily derepressed during development in
      normal cells, and qualitatively by modifications of the nucleotidic sequence of
      structural genes leading to an increase of the chelating ability of the coded
      metal ligand. 

PMID- 24277165
TI  - Influence of silver, mercury, lead, cadmium, and selenium on glutathione
      peroxidase and transferase activities in rats.
AB  - At the levels used in the experiments, mercury and silver significantly depressed
      the activity of glutathione peroxidase (assayed with either H2O2 or cumene-OOH)
      in rat tissues, whereas cadmium or lead had no effect on this activity. The most
      pronounced effects of mercury and silver on glutathione peroxidase were found in
      the liver and kidneys, with much less effect in the testes and erythrocytes.
      Similar trends for the effects of these metals were noted for tissue selenium
      levels. Silver and mercury significantly depressed the selenium concentrations,
      but cadmium and lead had no effect upon the selenium levels. Mercury and silver
      had no effect upon the activity of glutathione transferase in liver and testes,
      but mercury caused a significant initial increase of its activity in the kidneys.
      At no time did silver have any significant effect on its activity in this organ. 

PMID- 24277163
TI  - Magnesium (and trace substance) deficiencies in the pathogenesis of cancer.
AB  - Except for a few experimental models of magnesium (Mg)-deficiency-induced
      neoplasms, less attention has been paid in the past quarter century in the
      Western world to this macromineral than to the trace elements; e.g., selenium
      (Se) and zinc (Zn), and to vitamins, deficiencies of which are each considered
      probable factors in oncogenesis. Although early epidemiologic studies showed an
      inverse correlation between the amount of Mg in soil and water and the incidence
      of (gastric) cancer, and several animal studies supported the premise that Mg has
      a prophylactic effect against induction of cancer, other studies showed that Mg
      supplementation increased the growth of established experimental tumors. Thus,
      enthusiasm for this approach subsided. The early epidemiologic findings have
      since been confirmed, and there have been studies demonstrating the importance of
      Mg in maintaining immunocompetence, and others indicating that immunodeficiencies
      increase susceptibility to the development of cancer. Evidence has now accrued
      that indicates that Mg deficiency increases susceptibility to chemical oncogens.
      The abnormal metabolism of tryptophan (yielding a carcinogenic metabolite) that
      indicates functional or absolute pyridoxine deficiency is an indirect clue to Mg
      deficiency. Vitamin B6-activated enzymes require Mg as a cofactor. However, the
      early warnings against the use of Mg as part of an antineoplastic program against
      established cancer were justified, since rapidly metabolizing cells (such as
      cancers) are dependent on Mg.There are similarities between experiences with Mg
      and with Se and Zn. All three are required for normal metabolism; Se also
      protects against free radicals in the environment. Mg and Zn have increased
      established tumor growth, and their depletion has been applied to antineoplastic
      programs, with risks comparable to those of using antimetabolic agents. 

PMID- 24277166
TI  - Interaction between nickel and iron in the rat.
AB  - The interaction between nickel and iron was confirmed in rat metabolism. In a
      fully-crossed, two-way, three by four, factorially designed experiment, female
      weanling rats were fed a basal diet supplemented with iron at 0, 25, 50, and 100
      MUg/g and with nickel at 0, 5, and 50 MUg/g. The basal diet contained about 10 ng
      of nickel and 2.3 MUg of iron/g. After nine weeks, dietary iron affected growth,
      hematocrit, hemoglobin, plasma cholesterol, and in liver affected total lipids,
      phospholipids, and the contents of copper, iron, manganese, and zinc. By
      manipulating the iron content of the diet, effects of dietary nickel were shown
      in rats that were not from dams fed a nickel-deprived diet. Nickel affected
      growth, hematocrit, hemoglobin, plasma alkaline phosphatase activity, plasma
      total lipids, and in liver affected total lipids, and the contents of copper,
      manganese, and nickel. The interaction between nickel and iron affected
      hematocrit, hemoglobin, plasma alkaline phosphatase activity, and plasma
      phospholipids, and in liver affected size, content of copper, and perhaps of
      manganese and nickel. In severely iron-deficient rats, the high level of dietary
      nickel partially alleviated the drastic depression of hematocrit and hemoglobin,
      and the elevation of copper in liver. Simultaneously, high dietary nickel did not
      increase the iron level in liver and was detrimental to growth and appearance of
      severely iron-deficient rats. In nickel-deprived rats fed the borderline iron
      deficient diet (25 MUg/g) hematocrit and hemoglobin also were depressed. However,
      5 MUg Ni/g of diet were just as effective as 50 MUg Ni/g of diet in preventing
      those signs of nickel deprivation. The findings in the present study suggested
      that nickel and iron interact with each other at more than one locus. 

PMID- 24277167
TI  - Effect of dietary nickel and iron on the trace element content of rat liver.
AB  - The level and/or form of dietary iron, dietary nickel, and the interaction
      between them affected the trace element content of rat liver. Livers were from
      the offspring of dams fed diets containing 10-16 ng, or 20 MUg, of nickel/g.
      Dietary iron was supplied as ferric chloride (30 MUg/g) or ferric sulfate (30
      MUg, or 60 MUg). In nickel-deprived rats fed 60 MUg of iron/g of diet as ferric
      sulfate, at age 35 days, levels of iron and zinc were depressed in liver and the
      level of copper was elevated. At age 55 days, iron was still depressed, copper
      was still elevated, but zinc also was elevated. In rats fed 30 MUg of iron/g of
      diet as ferric chloride, liver iron content was higher in nickel-deprived than in
      nickel-supplemented rats at 30, but not at 50, days of age. Also manganese and
      zinc were lower in nickel-deprived than in nickel-supplemented rats at age 35
      days if their dams had been on experiment for an extended period of time (i.e.,
      since age 21 days). Thus, the levels of copper, iron, manganese, and zinc in
      liver were affected by nickel deprivation, but the direction and extent of the
      affects depended upon the iron status of the rat. 

PMID- 24277168
TI  - Change in apparent and true absorption and retention of dietary zinc with age in
      rats.
AB  - Two groups of 16 rats each were fed the same diet with 12.9 ppm Zn. Nine days
      after each animal was injected with(65)Zn for assessing fecal zinc of endogenous
      origin, zinc intake and excretion were determined for a six-day period at the age
      of about five (group I) and nine (II) weeks. At mean growth rates of 5.1 and 5.2
      g/day, food consumption per gram of gain was 2.01 g in group I vs 2.86 g in II.
      Overall, zinc retention amounted to 21 vs 25 MUg Zn/g of gain. Apparent
      absorption averaged 92 vs 74% of Zn intake (132 vs 189 MUg/day), while true
      absorption averaged 98 vs 92%. It was concluded that endogenous fecal zinc
      excretion was limited to the indispensable loss (F em) in group I (7 MUg/day),
      while it exceeded this minimum loss in group II (33 MUg/day). True retention,
      which reflected total zinc utilization (true absorption times metabolic
      efficiency), was derived from apparent absorption plusF em (11 MUg/day for group
      II according to the greater metabolic body size of the rats). It averaged 98% of
      Zn intake in group I vs 80% in group II. The mean metabolic efficiency was 100%
      vs 87%. The conclusion was that these marked differences between age groups in
      utilizing the dietary zinc reflected the efficient homeostatic adjustments in
      absorption and endogenous excretion of zinc to the respective zinc supply status.

PMID- 24277169
TI  - Zinc-induced synthesis of low molecular weight zinc-binding protein by human
      lymphocytes.
AB  - Incubation of human peripheral blood lymphocytes with zinc transferrin (with or
      without phytohemagglutinin) induces the synthesis of protein that elutes from a
      Sephadex G-75 column at aV e/V o value corresponding to a molecular weight of
      6600. Synthesis depends on the concentration of zinc transferrin in the medium
      and is sensitive to actinomycin D. Detectable synthesis occurs 5h after
      initiation of lymphocyte culture and plateaus at 24-30h. Polyacrylamide gel
      electrophoresis of the zinc-induced protein showed two closely moving bands, both
      of which show immunologic identity to rat liver metallothionein. Partial
      characterization of this protein yielded the following results: absorbance
      maximum at 220 nm; zinc content of 5.8 mol/6600 daltons; sulfhydryl content of
      20.2 mol/6600 daltons. Additionally, synthesis of zinc-induced protein is altered
      in both chronic lymphocytic leukemic and acute lymphoblastic leukemic
      lymphocytes. 

PMID- 24277170
TI  - On skepticism and faith.

PMID- 24277171
TI  - Humanistic psychotherapy assumptions and christian counseling.
AB  - This article examines eight assertions about the nature of humanistic
      psychotherapy which may be congenial with certain broad assertions or emphases of
      the Christian tradition (and, thus, Christian counseling). The humanistic
      assertions are that the focus of psychotherapy should be on the client's
      immediate experiencing which provides trustworthy self-knowledge, that freedom is
      real, that the proper therapist role is that of facilitator, that new ways of
      client thinking and acting are to be encouraged, that the body must receive
      therapeutic attention, and that honest mutual communication is critical.
      Christian emphases for which these are relevant include Old and New Testament
      understandings of the inner experience of God, the ongoing creative activity of
      God, individual responsibility before God, the unity of the individual, and how
      healing takes place. 

PMID- 24277172
TI  - Martin Buber's relevance to institutional mental health care.
AB  - A Buberian perspective on problems related to the establishment of therapeutic
      environments on mental hospital wards is offered. Depersonalization and over
      reliance on a medical treatment orientation in human relationships are identified
      as central problem areas in mental hospitals. The therapeutic community is
      identified as a major alternative model to respond to these problem areas.
      Difficulties in applying the therapeutic community model are identified. Buber's
      social philosophy, especially his interpretations of spiritual crisis, cultural
      crisis, structural renewal, and genuine dialogue, are identified as useful tools
      to clarify and resolve those difficulties. 

PMID- 24277173
TI  - California psychologists' religiosity and psychotherapy.
AB  - Forty-seven randomly selected California clinical psychologists were surveyed to
      examine the effect religious or spiritual orientation has on the practice of
      psychotherapy. This included an assessment of ideology, attitudes toward
      religiosity, affiliation with organized religion, dimensions of religiousness,
      and use of clinical interventions of a religious nature. The majority of these
      psychologists were found to address religious and spiritual issues in their
      personal lives, to respect the function religion serves in peoples' lives, and to
      address religious and spiritual issues in professional practice. The majority of
      these psychologists use interventions of a religious nature. Very limited
      training occurs respective of religious and spiritual concerns; 81% reported that
      religious or spiritual issues were rarely or never discussed in the course of
      their graduate education and training. 

PMID- 24277174
TI  - Sin, narcissism, and the changing face of conversion.
AB  - Noting that current psychological discussions of conversion give far less
      attention to the "sense of sin" than did William James and his contemporaries,
      this article argues for renewed attention to sin and its role in the conversion
      experience. Using data from a survey of Christian laity on their attitudes toward
      the traditional deadly sins, the author concludes that the sins that trouble men
      and women today involve their narcissistic needs. As many seek relief from the
      "tyranny" of their narcissistic needs, the author contends that what would
      constitute conversion for them is the "transformation" of narcissism. Typical
      candidates for such conversion are adults, not adolescents. 

PMID- 24277176
TI  - Editorial.

PMID- 24277175
TI  - Raltegravir: a review of its use in the management of HIV-1 infection in children
      and adolescents.
AB  - Raltegravir (ISENTRESS((r))) is an HIV-1 integrase strand transfer inhibitor that
      is well established as a component of highly active antiretroviral therapy
      regimens for the treatment of adults with HIV-1 infection, and has recently been
      approved for the treatment of HIV-1-infected children and adolescents aged 2-18
      years. A new chewable formulation has been introduced and results of a
      pharmacokinetic study have led to the establishment of dosages for this
      formulation for children. In a phase I/II, open-label, multicentre, clinical
      trial, raltegravir (administered as the chewable or the film-coated tablet) in
      combination with optimized background antiretroviral therapy was an effective
      treatment for treatment-experienced children and adolescents with HIV-1
      infection, in terms of virologic measures of efficacy (i.e. a decrease of in HIV
      1 RNA levels of >=1 log(10), or an HIV-1 RNA level of <400 copies/mL at the 24
      week primary efficacy assessment), with virologic efficacy sustained at the 48
      week assessment. Immunologic improvements (increases from baseline in CD4+ cell
      counts) were also observed. As a component of combination therapy, raltegravir
      was generally well tolerated over a period of up to 48 weeks. Raltegravir is an
      important new option for the treatment of children and adolescents with HIV-1
      infection, and the introduction of a new chewable formulation (allowing dosage
      flexibility) extends its benefits to the treatment of younger children.

PMID- 24277177
TI  - Controlled release of polypeptides and other macromolecules.
AB  - The use of polymeric matrices for the controlled release of polypeptides and
      other macromolecular drugs is reviewed. Three principal mechanisms of release
      include diffusion of the polypeptide through the polymer, erosion of the polymer
      matrix, and the application of magnetic fields to force more drug out of the
      matrix. The diffusion controlled systems generally utilize ethylene-vinyl acetate
      copolymer. The advantage of these systems is facile manipulation of the pore
      structure to obtain desired release kinetics. Release of many different
      polypeptides from these systems for periods of months has been demonstrated.
      Bioerosion provides the advantage that the polymer system does not need to be
      retrieved. Magnetism provides a mechanism whereby desired increases and decreases
      in polypeptide release rates can be achieved on demand. 

PMID- 24277179
TI  - New lipophilic terbutaline ester prodrugs with long effect duration.
AB  - Two new lipophilic terbutaline ester prodrugs - the biscarbamate bambuterol
      (pINN) and the cascade ester D 2438 - have been designed with the goal to achieve
      enhanced absorption and high hydrolytic stability during first-pass in order to
      prolong the effect duration of the parent compound. Bambuterol, the bis-N,N
      dimethyl-carbamate of terbutaline, displays improved hydrolytic stability, partly
      by inhibition of its own hydrolysis, and has been shown to survive first-pass
      hydrolysis in the dog to a high degree. Bambuterol per se is inactive; however,
      after oral administration to guinea-pigs, the ED50 value for protection from
      histamine-induced bronchospasm is similar to that of terbutaline. Moreover, the
      terbutaline plasma level-time profile after oral doses of bambuterol in dogs is
      significantly prolonged. The cascade ester of terbutaline (D 2438), derived from
      p-pivaloyloxybenzoic acid, was designed to undergo first-pass hydrolysis and
      conjugation at the p-pivaloyloxybenzoic acid moiety; i. e. distal from the active
      resorcinol moiety in terbutaline. The prodrug itself is active in the isolated
      guinea-pig trachea and displays prolonged effect duration both after inhalation
      in guinea-pigs and after oral administration in dogs. The cascade ester prodrug
      (D 2438) has a somewhat shorter effect duration than bambuterol in these species.

PMID- 24277178
TI  - The potential of nucleotide analogs as inhibitors of retroviruses and tumors.
AB  - The biologically active form of most purine or pyrimidine analogs is the
      nucleoside 5'-mono, di- or triphosphate. The nucleoside form is most often
      administered because of the ease with which it penetrates cells by facilitated
      transport. However, many nucleoside derivatives fail to exhibit significant
      antiviral or antitumor activity because they are not phosphorylated by cellular
      enzymes to the active nucleotide form. In this review, the potential use of
      suitable nucleotide analogs as selective inhibitors of ribonucleotide reductase
      and viral reverse transcriptase is considered. Masked nucleotides such as
      phosphoramidates or methyl phosphates could be employed to allow transport across
      cellular membranes. Furthermore, phosphonocarboxamide, phosphonoformate or
      sulfamidophosphoramidate may mimic nucleotide di- and triphosphates. Tumor cells
      and virally infected cells are often more permeable to nucleotides and their
      analogs than normal cells, which could provide a therapeutic advantage. There
      could be considerable therapeutic potential for nucleotide analogs that can
      penetrate the tumor cell membranes and that are resistant to enzymatic hydrolysis
      and are non-incorporable into DNA or RNA. 

PMID- 24277180
TI  - Influence of bloodflow on the absorption of theophylline from the jejunum of the
      rat.
AB  - The influence of the jejunal bloodflow on the absorption of theophylline was
      investigated. The bloodflow through a segment under investigation was varied by
      changing the systemic blood pressure by means of a donor blood infusion into the
      jugular vein or by an infusion of isoprenaline or levarterenol into a femoral
      vein, and was measured by collecting the venous outflow from the intestinal
      segment. Above a bloodflow of approximately 0.40 ul/min/cm the flux/ flow ratio
      is reduced, and it is proposed that above this flow the intestinal epithelium
      provides the rate limiting step in the absorption of theophylline. When the
      bloodflow was held low for a prolonged time, the flux of theophylline decreased.
      The absorptive site bloodflow was calculated to be 18 % of the total bloodflow
      through the segment under investigation. 

PMID- 24277181
TI  - The Hypolipidemic Activity of N-(p-Chlorobenzoyl)-sulfamate in Rodents and its
      Effect on Lipid Metabolism.
AB  - N-(p-Chlorobenzoyl)-sulfamate was observed to produce potent hypolipidemic
      activity in rodents at 10 to 60 mg/kg/day. Liver phosphatidate phosphohydrolase
      and sn-glycerol-3-phosphate acyl transferase activities were suppressed by the
      agent in vitro and in vivo, and ATP dependent citrate lyase and acetyl CoA
      carboxylase activities were reduced in vivo. N-(p-Chlorobenzoyl)-sulfamate
      reduced cholesterol, neutral lipids, and triglycerides in the liver and increased
      excretion of cholesterol and neutral lipids in the bile and feces. Drug treatment
      reduced the neutral lipid and triglyceride content of serum chylomicrons, VLDL
      and LDL, and cholesterol content was reduced in the chylomicron and HDL
      fractions. 

PMID- 24277182
TI  - Pharmacokinetics of anthracyclines in dogs: evidence for structure-related body
      distribution and reduction to their hydroxy metabolites.
AB  - The pharmacokinetic disposition of the anthracyclines, adriamycin (doxorubicin),
      daunorubicin, 4'-epi-adriamycin, carminomycin, and 4-demethoxy-daunorubicin, and
      the formation of their reduced C13 hydroxy metabolites were studied in dogs. The
      presence of a C14hydroxy group (adriamycin and 4'epi-adriamycin) drastically
      reduces the appearance of the C13 hydroxy metabolites in plasma. Substitution of
      the C4-H with C4-OH and C4-OCH3, in this rank order, decreases the area under the
      plasma concentration-time curves of the parent compounds and their C13 hydroxy
      metabolites. 

PMID- 24277183
TI  - The analgesic activity of neo-kyotorphin: a newly identified pentapeptide from
      bovine brain.
AB  - Analgesic effects of a novel pentapeptide from bovine brain, termed neo
      kyotorphin (Thr-Ser-Lys-Tyr-Arg), were determined in mice after intracisternal
      injection. Neo-kyotorphin showed a dose-dependent analgesia with an ED50 value of
      195 nmol/ mouse. This effect was not blocked by naloxone pretreatment. 

PMID- 24277184
TI  - Continuous measurements of ATP secretion in vivo.
AB  - Blood was withdrawn continuously from femoral veins of anesthetized rabbits at a
      rate of 0.07 ml/min. Sodium citrate was pumped into the blood to prevent
      coagulation, and luciferin-luciferase reagent was added to permit the continuous
      detection of extracellular ATP. Subsequently, the red blood cells were lysed and
      the platelet count was recorded continuously. Injection of platelet activating
      factor or collagen into rabbit ear veins caused an almost immediate but short
      lived increase in extracellular ATP with a simultaneous but more prolonged
      decrease in the platelet count. Although both the endoperoxide analog 9,11-azo
      PGH2 and ADP also decreased the platelet count, little extracellular ATP was
      detected after the azo-PGH2 and none after ADP. These studies demonstrate that
      those agents that cause platelet secretion from rabbit platelets in vitro also
      cause secretion in vivo. The method described should be useful in evaluating the
      capacity of antithrombotic drugs to modify platelet secretion in vivo. 

PMID- 24277185
TI  - High pressure liquid chromatographic analysis of metoclopramide in serum.
AB  - Metoclopramide has recently been approved at dose levels of 1 to 2 mg/kg for the
      treatment of nausea and vomiting resulting from cancer chemotherapeutic agents. A
      rapid, sensitive reverse phase HPLC quantitative procedure for metoclopramide in
      serum is described. The method involves a single-step extraction of
      metoclopramide and disopyramide (internal standard) from alkalinized serum into
      benzene and utilizes a reverse-phase C-8 system with a mobile phase of 11:22:66,
      methanol: acetonitrile: pH 3.7 acetate buffer, and UV detection at 268 nm. The
      method is highly reproducible and has a limit of sensitivity of 2.5 ng/ml from a
      2.0 ml serum sample. The method has been successfully applied to clinical
      pharmacokinetic studies involving administration of IV oral metoclopramide to
      cancer patients receiving highly emetogenic cis-diamminedichloroplatinum. 

PMID- 24277186
TI  - WIN 44,441: A Stereospecific and Long-Acting Narcotic Antagonist.
AB  - The opiate antagonist WIN 44,441-3 is a potent, stereospecific antagonist of mu,
      delta, and kappa opiate receptors. This antagonist activity is of long duration
      (> 4 h) with no agonist activity being observed. It therefore appears that WIN
      44,441-3 will be a useful long-acting opiate antagonist for in vivo studies. 

PMID- 24277187
TI  - Factors affecting the determination of unbound carbamazepine concentrations in
      plasma.

PMID- 24277188
TI  - Who speaks for the future?

PMID- 24277189
TI  - Decreased posterior cruciate and altered collateral ligament loading following
      ACL transection: a longitudinal study in the ovine model.
AB  - Although ACL deficiency is shown to lead to joint degeneration, few quantitative
      data are reported on its effect on soft tissue structures surrounding the knee
      joint, specifically, the posterior cruciate and collateral ligaments. The
      kinematics of the stifle joint of sheep (N = 5) were measured during "normal"
      gait, as well as 4 and 20 weeks after ACL transection. These motions were
      reproduced using a unique robotic manipulator and the loads borne by PCL, MCL,
      and LCL during gait were determined. Our results demonstrated a significant
      decrease in mean PCL loads 20 weeks post-ACL injury, at hoof-strike (0% of gait,
      p = 0.034), hoof-off (66% of gait, p = 0.006), peak-swing (85% of gait, p =
      0.026), and extension-before-hoof-strike (95% of gait, p = 0.028). Mean MCL loads
      did not significantly increase following ACL transection, maybe due to large
      between-animal variation. Finally, mean LCL loads indicated a significant
      decrease (p < 0.047) at 20 weeks across the entire gait cycle. From a clinical
      perspective, the load redistributions observed in cruciate and collateral
      ligaments following ACL injury indicate that these tissues can carry/adapt to the
      altered mechanical environment of the joint. The considerable variability in the
      magnitudes of change following ACL injury among animals also simulates clinical
      variability in humans after trauma.

PMID- 24277190
TI  - Expression of nodule-specific genes in Phaseolus vulgaris L.
AB  - The identification of some nodule-specific host proteins (nodulins) from common
      bean (Phaseolus vulgaris L.), a tropical ureide-transporting legume, is
      described. Particularly, the existence and developmental expression of several
      abundant nodule-specific transcripts of P. vulgaris are shown, including
      leghemoglobin, nodulespecific uricase and a group that in vitro translates into a
      cluster of about 30 kDa products. The expression pattern of nodulins in effective
      (Fix(+)) nodules compared to ineffective (Fix(-)) ones is also presented. The
      modified expression of main nodulins observed between these nodules indicates
      that different levels and/or factors associated with their regulation are
      involved. The intracellular infection by Rhizobium as a decisive step in the
      induction of some P. vulgaris nodulins is discussed. 

PMID- 24277191
TI  - Developmental biochemistry of cottonseed embryogenesis and germination. XIX.
      Sequences and genomic organization of the alpha globulin (vicilin) genes of
      cottonseed.
AB  - The alpha globulin storage protein genes of cotton are found to exist as gene
      tandems that contain a gene from each of the 2 alpha globulin subfamilies
      separated by a spacer region of about 2700 or 3400 base pairs. Three different
      tandems have been identified by restriction endonuclease mapping of genomic DNA.
      A cDNA that is different from the genes of the tandems in map sites and/or in
      nucleotide sequence indicates that a fourth tandem probably exists in the cotton
      genome. Since the species of cotton used here (Gossypium hirsutum) is an
      amphidiploid, it is likely that two of the tandems are contributed from each
      genome.Considerable divergence in nucleotide sequence (18%) and in derived amino
      acid sequence (28%) is found when the 2 genes of a sequenced tandem are compared.
      The sequence of the cDNA closely resembles one of the genes in the tandem showing
      only a 4% divergence in nucleotides and a 4.2% divergence in amino acids. Thus
      the 2 genes of each tandem represent a relatively ancient gene duplication that
      has given rise to the two alpha globulin subfamilies of cotton. Only one
      subfamily has a glycosylation site and the glycosylation of its derived proteins
      gives rise to the 2 molecular weight sets of alpha globulins seen on gel
      electrophoresis.Other basic features of these genes and their derived proteins
      are presented. 

PMID- 24277192
TI  - Expression of a gene for a light-harvesting chlorophyll a/b-binding protein in
      Chlamydomonas reinhardtii: effect of light and acetate.
AB  - In Chlamydomonas reinhardtii, the chlorophyll a/b-binding proteins of photosystem
      II are encoded in the nucleus by a small family of genes. We have studied the
      expression of one gene, which we call cabII-1, in a green-in-the-dark strain,
      which can synthesize chlorophyll in the dark or light, and in a yellow-in-the
      dark mutant strain, which is able to make chlorophyll only in the light. In
      light/dark synchronized cultures of both strains, cabII-1 mRNA abundance
      increases during the first 6 h of a 12-h light phase, remains high for several
      hours, then declines. A variety of illumination conditions have been used to
      analyze the cabII-1 mRNA increase: continuous or intermittent red, blue, or white
      light, with or without 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an
      inhibitor of photosystem II. Our results suggest that light induces increased
      cabII-1 transcript abundance in two ways: 1) by virtue of its role in the light
      reactions of photosynthesis and 2) by a blue lightstimulated mechanism which is
      independent of photosynthesis.We have also examined the role of acetate in
      regulating cabII-1 mRNA levels in the dark. In both green- and yellow-in-the-dark
      strains, 15 mM Na-acetate, added to synchronized cells in the dark, induces an
      increase in cabII-1 mRNA abundance with a temporal accumulation pattern very
      similar to that induced by continuous white light. We suggest that by providing
      an energy source, acetate stimulates cellular growth, cell cycle progression, and
      increased cabII-1 mRNA abundance. Interestingly, in cells exposed to light,
      acetate inhibits the light-induced increase in cabII-1 mRNA abundance by a
      mechanism which is not yet understood. 

PMID- 24277193
TI  - cDNA cloning of beta-tubulin gene and organization of tubulin genes in Vigna
      radiata (mung bean) genome.
AB  - We isolated an almost full-length cDNA clone containing beta-tubulin gene from a
      partial cDNA library of mung bean using chicken cDNA as probe. Cross
      hybridization with chicken beta-tubulin cDNA and positive hybridization-selection
      and translation of mung bean mRNA established that this clone contains beta
      tubulin sequences. We studied the organization of tubulin genes in mung bean. In
      this plant tubulin genes are organized in tandem repeats of alternating alpha-
      and beta-tubulin genes. The 5.6 kb basis repeat unit which contains both alpha-
      and beta-tubulin genes is repeated twenty times per haploid genome. 

PMID- 24277194
TI  - Assessment of the efficiency of cotransformation of the T-DNA of disarmed binary
      vectors derived from Agrobacterium tumefaciens and the T-DNA of A. rhizogenes.
AB  - Co-transfer of Agrobacterium rhizogenes T-DNA and T-DNA from the A. tumefaciens
      binary vector pBin19 (Bevan, 1984) was studied in detail using Nicotiana rustica.
      High frequencies of co-transfer of T-DNA's were observed, even when no selection
      pressure was exerted. Increased levels of pBin19 T-DNA were found in hairy root
      cultures with selection at higher levels of kanamycin sulphate (50-200 MUg ml(
      1)). Several other species were also transformed by A. rhizogenes carrying pBin19
      and A. rhizogenes harbouring a different binary factor, pAGS125 (Van den Elzen et
      al., 1985), was used to transform N. rustica hairy roots to confer hygromycin B
      resistance. 

PMID- 24277195
TI  - Segregation of T-DNA copies in the progeny of a regenerant plant from a mannopine
      positive hairy root line.
AB  - We have analyzed opine content, T-DNA content, and developmental features of one
      hairy root culture line and its progeny. Opine-positive progeny still have the
      hairy root phenotype and have essentially the same T-DNA structure as the
      parental plant. Opineless progeny do not exhibit the hairy root phenotype. Some
      of them do not contain any T-DNA sequences, whereas others contain only the left
      part of T-DNA. These results are compatible with the hypothesis that, in the
      hairy root line analyzed, the left part of T-DNA is integrated independently from
      the core T-DNA and can therefore segregate during sexual reproduction. 

PMID- 24277196
TI  - Identification, purification, and characterization of pathogenesis-related
      proteins from virus-infected Samsun NN tobacco leaves.
AB  - Ten pH-3 soluble, low-molecular-weight pathogenesis-related proteins (PRs) were
      found to accumulate in leaves of tobacco cv. Samsun NN reacting hypersensitively
      to tobacco mosaic virus. Besides the previously characterized PRs 1a, 1b, 1c and
      2, these proteins were provisionally designated N, O, P, Q, R, and S in order of
      decreasing electrophoretic mobility in native polyacrylamide gels. Two
      dimensional gel electrophoresis indicated that the PRs consist of single
      polypeptides, except for R, which is composed of two components with slightly
      different molecular weights. Estimated molecular weights in SDS-containing gels
      were: PRs 1a and 1b 17 kD, 1c 16.5 kD, 2 31 kD, N 33 kD, O 35 kD, P 27 kD, Q 28
      kD, R 13 and 15 kD, and S 25 kD. However, based on their elution from gel
      filtration columns and relative moblities in native gels of different acrylamide
      concentrations, P and Q appeared to have molecular weights similar to those of
      the PR 1 group. Upon chromatofocusing no additional components were resolved. The
      PRs were eluted between pH 7 and 4; except for R, their pIs, as judged from
      isoelectric focusing, appeared to lie in the range from pH 4 to 5.2. In the
      presence of 6 M urea PR 1a was split into two components, one of which was
      strongly retarded on gels, as were P and Q. None of the PRs was detected when
      gels were stained for glycoproteins.By combinations of gel filtration, DEAE
      cellulose chromatography, and chromatofocusing, PRs 1a, 1b, 1c, 2 and N were
      purified, their amino acid compositions determined, and antisera raised against
      each of these components. By Western blotting, antisera against either PR 1a, 1b,
      or 1c reacted with each of the components of the PR 1 group, as well as with PR
      S. Similarly, the antisera against either PR 2 or N reacted with both 2 and N, as
      well as with O and R. On the basis of major similarities in molecular weight
      characteristics, amino acid compositions, and serological relationships, it is
      proposed to classify tobacco PRs into five groups: 1: PRs 1a, 1b, and 1c; 2: 2a
      (formerly 2), 2b (N), and 2c (O); 3: 3a (P), and 3b (Q); 4: 4a and 4b (the two
      components of R); and 5: PR 5 (S). 

PMID- 24277197
TI  - Characterization of a class of small auxin-inducible soybean polyadenylated RNAs.
AB  - Four new auxin-responsive RNAs from soybean (Glycine max (L.) Merr., var. Wayne)
      are described. The RNAs were identified by hybridization to three cDNA probes
      obtained from a library enriched for sequences which increase in abundance within
      60 min after 2,4-D (2,4-dichlorophenoxyacetic acid) treatment. These RNAs appear
      to define a new class of small (i.e. approximately 550 nucleotides) RNAs that
      respond extremely rapidly to application of exogenous auxin. In excised
      elongating hypocotyl sections, an increase in the abundance of these RNAs can be
      detected 2 to 5 min after treatment with 50 MUM 2,4-D. This response is half
      maximal after 10 min and reaches steady state in 60 min. RNA blot analysis shows
      that these RNAs are expressed differentially in various parts of the seedling.
      The degree of inducibility by auxin is also organ-specific, with the elongating
      hypocotyl being the most responsive of the organs tested. The RNAs display
      identical response specificities with one exception. Accumulation of one RNA,
      designated 10A, is completely abolished by simultaneous addition of cycloheximide
      and 2,4-D. This RNA also displays a different 2,4-D dose response than other RNAs
      examined. These results suggest that more than one mechanism is involved in rapid
      modulation of gene expression by auxin. 

PMID- 24277198
TI  - An auxin-induced polypeptide in dicotyledonous plants.
AB  - Antisera were raised to a 70-kD (kilodalton) soybean (Glycine max) protein
      encoded by a 2,4-dichlorophenoxyacetic acid (2,4-D) inducible mRNA, GH3. These
      antisera have been used to probe protein blots to study the kinetics and
      specificity of the GH3 induction response as well as the species specificity and
      intracellular location of the protein. Detectable levels of the GH3 protein are
      induced by 2,4-D within 2 h in elongating hypocotyl sections, root sections, and
      etiolated plumules, and within 30-60 min in soybean suspension cells. Synthesis
      of the GH3 protein is induced by a variety of auxins. Other plant hormones such
      as gibberellic acid, cytokinin and ethylene added with or whithout 2,4-D do not
      alter the level of GH3 protein induction. The GH3 protein is found only in the
      S100 fraction and is not associated with the nucleus or cell wall. This antiserum
      also reacts with a 2,4-D-inducible 70-kD protein in other dicots. 

PMID- 24277199
TI  - Molecular characterization of the virulence gene virA of the Agrobacterium
      tumefaciens octopine Ti plasmid.
AB  - The virulence loci play an essential role in tumor formation by Agrobacterium
      tumefaciens. Induction of vir gene expression by plant signal molecules is solely
      dependent on the virulence loci virA and virG. This study focused on the virA
      locus of the octopine type Ti plasmid pTi15955. The nucleic acid sequence of a
      5.7-kilobase fragment encompassing virA was determined. Genetic analysis of this
      region revealed that virA contains one open reading frame coding for a protein of
      91 639 daltons. Immunodetection with antibodies raised against a 35-kDa VirA
      fusion protein produced in E. coli identified by the VirA product in wild-type
      Agrobacterium cells. Moreover, it is shown that the VirA protein is located in
      the cytoplasmic membrane fraction of Agrobacterium. These data confirm the
      proposed regulatory function of VirA whereby VirA acts as a membrane sensor
      protein to identify plant signal molecules in the environment. The proposed
      sensory function of VirA strikingly resembles the function of the chemotaxis
      receptor proteins of E. coli. 

PMID- 24277200
TI  - Use of telemedicine to manage severe ischaemic strokes in a rural area with an
      elderly population.
AB  - The rural district of the Meuse (East France) has a high number of elderly
      patients for whom prognosis of ischaemic strokes is poor with high-haemorrhagic
      transformation risk of intravenous tissue plasminogen activator (rt-PA). This
      disadvantage is made worse by the distances a patient has to travel to the
      nearest stroke unit. We set out to assess the effectiveness of a telestroke
      system implemented in this area. Between October 2010 and February 2012, data
      from each "tele-expertised" patient were collected. 53 patients were examined.
      Diagnosis of ischaemic stroke was confirmed in 43 cases (81 %), and intravenous
      rt-PA treatment performed in 21 cases (40 %). In the treated patient group,
      median age was 73 years, with 29 % of octogenarians. Baseline National Institutes
      of Health Stroke Scale (NIHSS) was 16, with 29 % >= 20. The median onset to
      needle time was 169 min, and the median door to needle time was 69 min.
      Intracranial haemorrhage occurred in 3 cases (14 %), and was symptomatic in two
      (10 %). At 3 months, median NIHSS was 6, 6 patients (29 %) presented a favourable
      outcome (modified Rankin scale <= 1) and 3 (14 %) had died. In rural areas, for
      elderly patients with severe ischaemic strokes, telemedicine appears to be a way
      of improving accessibility and benefits of rt-PA treatment.

PMID- 24277201
TI  - Generalized epilepsy in a patient with myotonic dystrophy type 2.

PMID- 24277202
TI  - Homozygosity and severity of phenotypic presentation in a CADASIL family.
AB  - Most of causative mutations of the cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) are missense point
      mutations either creating or deleting one cysteine residue, inherited in a
      heterozygous state. Only few homozygous patients are reported to date and some of
      them showed phenotypic peculiarities. We here describe a CADASIL family in which
      a member showed homozygous mutation and compare its clinical profile with five
      subjects throughout three generation of the pedigree, carrying the same mutation
      in heterozygosity. The index patient was a 44-year-old Italian man, born from
      consanguineous parents (first cousins). Symptoms started at 23 years and
      progressing with recurrent ischemic stroke episode. Diffuse leukoencephalopathy
      and a severe cognitive impairment were evident, GOMs were detected in skin
      specimens and a homozygous p.Cys183Ser mutation of the NOTCH3 gene was found.
      Among the other five heterozygous relatives for the same mutation, both parents
      developed stroke in advanced age and all the others were clinically asymptomatic.
      We discuss these findings in relationship to previous data from the literature in
      CADASIL and in other dominant neurological disorders.

PMID- 24277203
TI  - Marked asymmetry of white matter lesions caused by chronic toluene exposure.

PMID- 24277204
TI  - Erythromycin pretreatment induces tolerance against focal cerebral ischemia
      through up-regulation of nNOS but not down-regulation of HIF-1alpha in rats.
AB  - The purpose of this study was to determine whether the antibiotic erythromycin
      induces tolerance against focal cerebral ischemia, and the possible underlying
      mechanism including the involvement of neuronal nitric oxide synthase (nNOS) and
      hypoxia-inducible factor-1alpha (HIF-1alpha). In rat focal cerebral ischemia
      models, we found that erythromycin preconditioning could significantly decrease
      the cerebral infarct volume and brain edema. Meanwhile, the neurological deficits
      from day 4 through 7 after surgery were also remarkably decreased after
      erythromycin preconditioning. Moreover, erythromycin preconditioning induced
      significantly increased nNOS levels and decreased HIF-1alpha levels in both mRNA
      and protein expression. This study for the first time indicated that erythromycin
      preconditioning could induce focal brain ischemic tolerance and attenuate brain
      injury of subsequent transient focal cerebral ischemia. The potential mechanism
      may be due to up-regulation of nNOS, but the HIF-1alpha system was not involved.

PMID- 24277206
TI  - Clinical, ultrastructural, and molecular studies in a patient with Kufs disease.

PMID- 24277205
TI  - Neuroprotective effect of ceftriaxone in a rat model of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of mortality and disability in
      children and young adults worldwide. Neurologic impairment is caused by both
      immediate brain tissue disruption and post-injury cellular and molecular events
      that worsen the primary neurologic insult. The beta-lactam antibiotic ceftriaxone
      (CTX) has been reported to induce neuroprotection in animal models of diverse
      neurologic diseases via up-regulation of GLT-1. However, no studies have
      addressed the neuroprotective role of CTX in the setting of TBI, and whether the
      mechanism is involved in the modulation of neuronal autophagy remains totally
      unclear. The present study was designed to determine the hypothesis that
      administration of CTX could significantly enhance functional recovery in a rat
      model of TBI and whether CTX treatment could up-regulate GLT-1 expression and
      suppress post-TBI neuronal autophagy. The results demonstrated that daily
      treatment with CTX attenuated TBI-induced brain edema and cognitive function
      deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can
      be reversed by treatment of CTX. In addition, we also found that CTX
      significantly reduced autophagy marker protein, LC3 II, in hippocampus compared
      to the TBI group. These results suggest that CTX might provide a new therapeutic
      strategy for TBI and this protection might be associated with up-regulation of
      GLT-1 and suppression of neuronal autophagy. 

PMID- 24277207
TI  - Chronic nutrient enrichment increases prevalence and severity of coral disease
      and bleaching.
AB  - Nutrient loading is one of the strongest drivers of marine habitat degradation.
      Yet, the link between nutrients and disease epizootics in marine organisms is
      often tenuous and supported only by correlative data. Here, we present
      experimental evidence that chronic nutrient exposure leads to increases in both
      disease prevalence and severity and coral bleaching in scleractinian corals, the
      major habitat-forming organisms in tropical reefs. Over 3 years, from June 2009
      to June 2012, we continuously exposed areas of a coral reef to elevated levels of
      nitrogen and phosphorus. At the termination of the enrichment, we surveyed over
      1200 scleractinian corals for signs of disease or bleaching. Siderastrea siderea
      corals within enrichment plots had a twofold increase in both the prevalence and
      severity of disease compared with corals in unenriched control plots. In
      addition, elevated nutrient loading increased coral bleaching; Agaricia spp. of
      corals exposed to nutrients suffered a 3.5-fold increase in bleaching frequency
      relative to control corals, providing empirical support for a hypothesized link
      between nutrient loading and bleaching-induced coral declines. However, 1 year
      later, after nutrient enrichment had been terminated for 10 months, there were no
      differences in coral disease or coral bleaching prevalence between the previously
      enriched and control treatments. Given that our experimental enrichments were
      well within the ranges of ambient nutrient concentrations found on many degraded
      reefs worldwide, these data provide strong empirical support to the idea that
      coastal nutrient loading is one of the major factors contributing to the
      increasing levels of both coral disease and coral bleaching. Yet, these data also
      suggest that simple improvements to water quality may be an effective way to
      mitigate some coral disease epizootics and the corresponding loss of coral cover
      in the future. 

PMID- 24277208
TI  - ABO incompatible liver transplants: room for cautious optimism.

PMID- 24277211
TI  - Research and publicity.

PMID- 24277209
TI  - National survey on excellence centers and reference centers for hypertension
      diagnosis and treatment: geographical distribution, medical facilities and
      diagnostic opportunities.
AB  - INTRODUCTION: Blood pressure (BP) control is poorly achieved in Western
      Countries, including Italy. Several interventions have been proposed at national
      and local level to improve BP control rate. AIM: This survey of the Italian
      Society of Hypertension (SIIA) is aimed at analysing the number and the
      distribution of reference centers and excellence centers for the diagnosis and
      treatment of arterial hypertension (hypertension centers) in Italy. METHODS: In
      October 2011, a specifically designed survey questionnaire was developed by SIIA
      National Committee, both to evaluate geographical distribution of the reference
      hypertensive population and to assess general requirements (days of activity,
      number of active physicians, medical facilities, diagnostic opportunities, use of
      electronic support), deemed necessary to identify an outpatient clinic as
      hypertension center in Italy. This questionnaire was locally distributed by
      regional coordinators of the Society and all collected data were centrally
      analysed by two independent study coordinators. RESULTS: From October 2011 to
      September 2012, 89 centers with clinical expertise in the diagnosis and treatment
      of hypertension provided data on their own activity. Among these, 45 (50.5 %)
      centers are located in the North, 20 (22.5 %) in the Center and 24 (27.0 %) in
      the South of Italy. Approximately 50 % of the hypertensive outpatients who are
      referred from general practitioners to hypertension centers are living in the
      province and about one third in the region. More than half of the centers is
      active for 3-5 days per week, and approximately 40 % of the centers have 3-5
      active physicians. Beyond outpatient visits for hypertension, these centers are
      able to organize day hospital (25 %), day service (29 %), or hospital admission
      (29 %) for advanced diagnostic evaluation or therapeutic interventions. All
      centers collect data from clinic and 24-hour ambulatory BP measurements, and
      almost all (95 %) centers are able to perform a standard 12-lead
      electrocardiogram. In addition, the majority of the centers are able to perform
      advanced diagnostic examinations, including echocardiography (74 %) or carotid
      Doppler ultrasound (71 %) analysis. Finally, 78 % of the centers use an
      electronic case report form, specifically designed for the clinical management of
      hypertensive patients. CONCLUSIONS: Although with some limitations related to the
      study methodology applied for data collection, the survey illustrates a quite
      unbalanced distribution of the hypertension centers, the majority of which are
      located in the North of Italy, with a medium-high standard of quality of care.
      This analysis may provide useful elements for a rational and effective use of
      existing resources, in order to improve BP control in our Country.

PMID- 24277210
TI  - I refused to perform abortions: you don't have to sacrifice your integrity to get
      ahead.

PMID- 24277212
TI  - Pyrrolo(l ,4)benzodiazepine Antitumor Antibiotics: Chemistry, Interaction with
      DNA, and Biological Implications.
AB  - The pyrrolo(l,4)benzodiazepine (P(1,4)B) antitumor antibiotics, anthramycin,
      tomaymycin, sibiromycin and the neothramycins A and B, are potent anticancer
      agents that form covalent adducts through the exocyclic amino group of guanine in
      DNA. This review describes the chemistry important for both the DNA reactivity
      and synthesis of the carbinolamine containing drugs and the strategy for
      elucidation of the three-dimensional form of the adduct with DNA. The high DNA
      sequence specificity as well as some of the observed biological consequences of
      DNA damage caused by these agents in human and yeast cells are rationalized
      through the proposed structure of the drug-DNA adducts. Parallel toxicological
      studies have led to a proposal for the underlying mechanism for the
      cardiotoxicity of certain members of this group of agents. A rationale for
      designing drugs which should retain their potent antitumor activity without the
      associated cardiotoxicity is also proposed. Lastly, the application of the
      P(l,4)B's as probes for monitoring drug binding to DNA and drug-induced
      conformational changes is described. 

PMID- 24277213
TI  - Drug interactions through binding to cytochrome p 450: the experience with h2
      receptor blocking agents.
AB  - H2-receptor blocking agents, such as cimetidine, ranitidine or oxmetidine, are
      consumed in large amounts often together with a variety of other drugs. There is
      increasing evidence that cimetidine interferes with the hepatic elimination of
      several drugs, thereby aggravating the effects of the comedication. Microsomal
      studies in vitro revealed that cimetidine binds in therapeutic concentrations to
      cytochrome P450, which may represent the primary mechanism for its ability to
      inhibit drug metabolism and thereby interact with other drugs. The structurally
      different ranitidine (replacement of the imidazole in cimetidine by a furan ring)
      is about five times as potent as a H2-receptor blocker and displays low affinity
      for binding sites on cytochrome P 450. Therefore, therapeutic doses of ranitidine
      do not impair the metabolism of other drugs. Preliminary data with oxmetidine
      suggest that it too does not interfere at the level of hepatic elimination. Thus,
      it is concluded that new therapeutic agents should be tested for their ability to
      bind to cytochrome P 450 to determine possible risks of drug interactions. 

PMID- 24277214
TI  - The hypolipidemic activity of benzenetricarboxylic acids in rodents.
AB  - A series of benzenetricarboxylic acids was shown to be potent hypolipidemic
      agents in rodents. Terephthalic acid proved to be one of the more potent agents,
      lowering serum cholesterol 42% and serum triglyceride 33 % at 20 mg/kg/day for 16
      days. The ability to lower serum lipids by this agent appeared to be due to
      multiple modes of action: (1) terephthalic acid suppressed the activities both in
      vivo and in vitro of a number of regulatory enzymes involved in cholesterol,
      fatty acid, and triglyceride syntheses; (2) the drug inhibited cholesterol
      absorption from the GI tract by 43 %; and (3) the drug accelerated lipid
      excretion in the feces leading to a reduction of cholesterol in the tissue.
      Terephthalic acid was effective in lowering lipids in normal and hyperlipidemic
      animals and possessed a safe therapeutic index.

PMID- 24277215
TI  - Effect of Uridine on the Metabolism of 5-Fluorouracil in the CD8F 1 Murine
      Mammary Carcinoma System.
AB  - The effect of uridine on the incorporation of 5-fluorouracil into RNA and the
      inhibition of DNA synthesis by the FdUMP block of thymidylate synthetase was
      studied in the CD8F1 murine mammary carcinoma system. The administration of
      exogenous uridine resulted in about a one third reduction of 5-fluorouracil in
      RNA of tumor and normal tissues. However, unlike thymidine, uridine was unable to
      reverse the early, partial inhibition of DNA synthesis. The amount of
      fluorouridine nucleotides and (5-fluorouracil)RNA formed in various tissues
      correlates with the level of orotate phosphoribosyl transferase activity
      suggesting that the major pathway for activation of 5-fluorouracil to nucleotide
      form in these tissues is via phosphoribosyl transferase. Enzyme preparations from
      three different murine tumors convert about 15 times as much 5-fluorouracil to
      FUMP as they do uracil to UMP. In contrast, the ratio of FUMP to UMP formed in
      enzyme preparations from gut and bone marrow is lower, 2-6 fold. However, in none
      of these tissues was the in vitro conversion of 5-fluorouracil to FUMP or
      incorporation into RNA substantially inhibited by uracil. Examination of tumor,
      gut and bone marrow uridine nucleotide pools showed that the thymidine-uridine-5
      fluorouracil schedule does increase uridine nucleotide pools. Thus, the reduction
      in 5-fluorouracil in RNA is probably not due to inhibition of the conversion of 5
      fluorouracil to FUMP by uracil (derived from phosphorylase cleavage of uridine)
      but, rather, is probably due to the elevated levels of UTP. We conclude that the
      protection from 5-fluorouracil toxicity afforded by the addition of uridine is
      due to the reduction in 5-fluorouracil in RNA rather than by reversal of the
      FdUMP block on thymidylate synthetase. 

PMID- 24277216
TI  - Pharmacodynamic measurements of methyl nicotinate percutaneous absorption.
AB  - The local kinetics of percutaneous absorption provide information of relevance to
      the treatment of skin diseases and to the potential efficacy of transdermally
      delivered chemotherapy for systemic effect. This paper describes two non-invasive
      procedures (laser Doppler velocimetry and photopulse plethysmography) which
      permit pharmacodynamic measurements of methyl nicotinate skin penetration to be
      made in vivo in man. The methods are sensitive to the local vasodilative action
      elicited by the nicotinic acid ester. Dose-response behavior as a function of
      time has been monitored (1) over the concentration range 5-100 mM, and (2) by
      variation of drug application time and administration area. At the higher
      concentrations used, the magnitude of the erythemal response is saturable, and
      the effect is then progressively prolonged by further increasing the applied
      dose. Analysis of the data permits assessment of (a) the kinetics of drug
      delivery to and depletion from the site of action, and (b) the hypothetical level
      of steady state drug input necessary to sustain 50 % of the maximum detected
      response. Measurements of the type described here may prove useful, therefore,
      for elucidating otherwise inaccessible aspects of transcutaneous kinetics in
      vivo. 

PMID- 24277217
TI  - Pharmacokinetic determinants in the design and evaluation of sustained-release
      dosage forms.
AB  - A new method employing the principle of superimposition was developed to aid in
      the formulation of sustained-release dosage forms. Independently absorbed
      components of a product, e.g., waxed pellets for an oral capsule, are
      administered separately and their plasma level-time profiles determined. Using a
      trial and error procedure, the ratios of pellets are varied to obtain a desired
      plasma level-time profile. The use of (1) time averaged plasma concentration-time
      data, (2) amount remaining to be absorbed (excreted) plots, and (3) cumulative
      amount absorbed (excreted) plots were all shown to be inappropriate for
      pharmacokinetic analyses in general, and evaluation of sustained-release products
      in particular. It was recommended that raw plasma concentration-time data be made
      available for sustained-released products, and that individual rate of absorption
      plots be used to assess absorption kinetics. It was concluded that much of the
      sustained-release pharmacokinetic data presently in the literature have been
      presented in such a manner, e.g. averaged data, as to be of limited value. 

PMID- 24277218
TI  - Proton magnetic resonance studies of the decomposition of 4
      hydroxycyclophosphamide, a microsomal metabolite of cyclophosphamide.
AB  - The proposed tautomeric equilibrium between the microsomal metabolite of
      cyclophosphamide, 4-hydroxycyclophosphamide, and the open chain aldophosphamide,
      and the subsequent facile beta-elimination to generate acrolein and phosphoramide
      mustard have been confirmed by proton magnetic resonance studies. When 4
      hydroxycyclophosphamide, initially maintained in CDC13 at -20 degrees C, was
      allowed to equilibrate at 15 degrees C, a singlet at 9.76 delta and a triplet at
      2.88 delta appeared concomitantly which were assigned to the aldehydic proton and
      the protons alpha to the carbonyl of aldophosphamide, respectively. Further
      reaction led to the appearance of several NMR signals that indicated the
      irreversible formation of acrolein (multiplet at 9.55 delta) and phosphoramide
      mustard. Polymerization occurred approximately 2 hours after the initiation of
      the reaction. The kinetic data of the reaction sequence are discussed. 

PMID- 24277219
TI  - Retinylnitrones: a new class of retinoids with chemopreventive action.
AB  - Retinoids containing a polar nitrone end group have been synthesized. This new
      class of extensively conjugated, open chain nitrones has been found to be
      effective in reversing the keratinization in hamster tracheal organ cultures. The
      highest activity was displayed by the retinylnitrone bearing the least bulky N
      alkyl substituent, i. e., methylnitrone 1; its activity level was comparable to
      that of all-trans retinoic acid. 

PMID- 24277220
TI  - Synthesis of 8-(3-Carboxy-l-methyl-propylammo)-6-methoxyquinoline: A Newly
      Characterized Primaquine Metabolite.
AB  - Primaquine (I), a 6-methoxy-8-aminoqumoline derivative used for the treatment of
      malaria has previously been shown to be metabolized to 8-(3-carboxy-l-methyl
      propylamino)-6-methoxyquinoline by both micro-organisms and laboratory rats.
      Reported herein is the synthesis of this novel metabolite. 

PMID- 24277221
TI  - Metabolism and distribution of primaquine in monkeys.
AB  - Rhesus monkeys were administered primaquine diphosphate (6.0 to 10.5 mg/kg,
      I.V.), and plasma samples were analyzed by high performance liquid chromatography
      for the presence of the unchanged drug and the major metabolite , 8-(3-carboxy-l
      methylpropylamino)-6-methoxyquinoline (II). Primaquine had an unusually high
      affinity for tissue compartments which produced a rapid initial drop in plasma
      concentration. Within 15 minutes, the plasma concentration of II far exceeded
      that of primaquine. 35 to 83 % of the primaquine dose was converted to II;
      moreover, metabolite II possessed much lower affinity for the tissue compartments
      than primaquine itself. 

PMID- 24277222
TI  - Editorial.

PMID- 24277223
TI  - "On the margins": A dialogue with Andrew Greeley.
AB  - This dialogue is between two priests who share common interests from different
      perspectives. One is an Episcopalian and a psychoanalytic psychotherapist. The
      other is a Roman Catholic and a sociologist widely known for his controversial
      novels and political commentaries. Their conversation primarily focuses on the
      latter's ministry-especially his investigations into paranormal experiences and
      his use of fiction as a homiletical avenue. They also discuss: Christian atheism;
      the Resurrection as a metaphor; Real Presence and liturgical sensibility;
      contemporary ecumenical trends; celibacy and tenures of active ministry; sexual
      equality and population control; religious addiction; and examples of the mythic
      impact of cinema. 

PMID- 24277224
TI  - Ritual and vulnerability.
AB  - Crises are viewed as direct challenges to one's communal patterns of living. The
      individual response to crisis(-es) is mediated by the "grand rituals of the
      culture." Ritual behaviors are adaptive behaviors. For the religious community,
      ritual becomes liturgy. Rite-as-liturgy is a profound statement about the meeting
      of the human and the divine. Ritual behaviors are understood as liturgical and/or
      sacramental responses to those crises that bring one to the brink of chaos. 

PMID- 24277225
TI  - Altruism and forgiveness as therapeutic agents in psychotherapy.
AB  - This article suggests that a more altruistic or other-directed perspective is as
      therapeutic for clients as a self-centered orientation which is more often
      promoted by psychotherapists. It also proposes that forgiveness may be an
      important therapeutic factor in helping clients deal with anger and resentment.
      Religious and spiritual teachings (especially those of Christianity), which have
      been greatly ignored by mental health professionals, are viewed as potentially
      valuable resources. 

PMID- 24277226
TI  - The moral lives of children: The thought of Robert Coles.
AB  - Robert Coles combines the insights of literature with the resources of medicine
      and psychiatry in order to understand and bring healing to people. Using the
      distinction between character and personality, Coles explores the active moral
      lives of children. To Coles, the moral purpose of the family is to develop
      character. Coles's contribution is not a new theoretical approach; rather, it is
      a literary documentary perspective that seeks to awaken and sensitize our moral
      imaginations. 

PMID- 24277227
TI  - Religion's encouragement and inhibition of psychological maturity.
AB  - The secure feelings that religious faith instills can help strengthen people
      against the anxieties experienced in life. They can strengthen people against
      anxiety in a mature and immature way. When religion makes people feel secure by
      providing an image of God that magically removes anxiety, rather than that
      stimulates the strength to make people feel confident enough to manage anxiety,
      then religion is of the latter type. However, even religion of this type can lead
      gradually to growth, rather then permanently to immaturity. It can temporarily
      free people of their anxieties in order to make them feel secure enough to
      confront the fears and manage the conflicts which, when they were anxious, they
      were unable to do. A clinical case is provided to demonstrate this process. 

PMID- 24277228
TI  - The religious and moral foundations of pastoral counseling.
AB  - This paper explores the significant issues related to the articulation of
      distinctions between pastoral counseling and the secular psychotherapies. The
      argument is made that pastoral counseling can be distinguished from the secular
      psychotherapies because the former is grounded in the moral vision of the
      religious traditions as well as the growing body of clinical knowledge the
      secular psychotherapies have made available to the culture. A dialectical model
      of moral inquiry is then presented as the most adequate for the pastoral
      counseling enterprise to carry out its inescapable moral task. 

PMID- 24277229
TI  - Newborn bloodspot results: predictive value of screen positive test for
      thalassaemia major.
AB  - AIM: There are limited published data on the performance of the percentage of
      haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the
      newborn period. This paper aims to analyse data derived from a national newborn
      bloodspot screening programme for sickle cell disease on the performance of
      haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the
      newborn period. METHODS: Newborn bloodspot sickle cell screening data from
      2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and
      Thalassaemia Screening Programme in England for the period 2005 to 2012 were also
      reviewed to identify any missed cases (4,599,849 babies). RESULTS: Within the
      cohort of 2,288,008 births, 170 babies were identified as screen positive for
      beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified
      through look-back methods and 119 prospectively identified from 4 screening
      laboratories. Among 119 babies with prospective data, 7 were lost to follow up
      and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a
      percentage of the total haemoglobin as a screening test for beta thalassaemia
      major in the newborn provides an estimated sensitivity of 99% (from the look back
      arm of the study) with a positive predictive value of 87% (from the prospective
      arm of the study). Excluding infants born before 32 weeks gestation, the positive
      predictive value rose to 95%. CONCLUSION: A haemoglobin A value of less than 1.5%
      is a reliable screening test for beta thalassaemia major in the newborn period.

PMID- 24277230
TI  - Peri-implant bone strains and micro-motion following in vivo service: a
      postmortem retrieval study of 22 tibial components from total knee replacements.
AB  - Biological adaptation following placement of a total knee replacements (TKRs)
      affects peri-implant bone mineral density (BMD) and implant fixation. We
      quantified the proximal tibial bone strain and implant-bone micro-motion for
      functioning postmortem retrieved TKRs and assessed the strain/micro-motion
      relationships with chronological (donor age and time in service) and patient
      (body weight and BMD) factors. Twenty-two tibial constructs were functionally
      loaded to one body weight (60% medial/40% lateral), and the bone strains and
      tray/bone micro-motions were measured using a digital image correlation system.
      Donors with more time in service had higher bone strains (p = 0.044), but there
      was not a significant (p = 0.333) contribution from donor age. Donors with lower
      peri-implant BMD (p = 0.0039) and higher body weight (p = 0.0286) had higher bone
      strains. Long term implants (>11 years) had proximal bone strains 900 uepsilon
      that were almost twice as high as short term (<5 years) implants 570 uepsilon.
      Micro-motion was greater for younger donors (p = 0.0161) and longer time in
      service (p = 0.0008). Increased bone strain with long term in vivo service could
      contribute to loosening of TKRs by failure of the tibial peri-implant bone.

PMID- 24277232
TI  - Search for neuro-endocrine markers (chromogranin A, synaptophysin and VGF) in
      breast cancers. An integrated approach using immunohistochemistry and gene
      expression profiling.
AB  - Discordant data are reported in the literature on the definition, incidence and
      clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour
      entity is currently assessed by immunohistochemistry (IHC) detecting "general" NE
      markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers
      have been considered as well. In the present study, in addition to CHGA and SYP,
      we investigated the expression of VGF, a neurotrophin-inducible gene, which is
      emerging as a new specific NE marker. In order to evaluate the differential
      expression of these neuro-endocrine markers in breast cancers, we conducted
      parallel immunohistochemical and gene expression analyses, using PCR, gene array
      and real-time quantitative PCR procedures. Data obtained in 28 cases were further
      validated with a meta-analysis of published datasets of 103 breast cancer cases.
      The value of IHC positivity (irrespective of the percentage of positive cells)
      was confirmed by over-expression of the related gene. However, the genetic
      approach emerged as more sensitive, showing over-expression of NE markers in a
      subset of IHC-negative carcinomas. In conclusion, the present study confirms, by
      a novel approach, the occurrence of NE differentiation in breast cancers. Over
      expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a
      significant fraction (approximately 10 %) of infiltrative breast cancers.

PMID- 24277231
TI  - Molecular features of follicular variant papillary carcinoma of thyroid:
      comparison of areas with or without classical nuclear features.
AB  - We aimed to compare the genetic background of different areas in follicular
      variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear
      changes. Sixteen cases of FVPTC were included in our study. All tumors were well
      demarcated from surrounding thyroid tissue and had both areas with nuclear
      features (WNF) and areas without nuclear features (WONF) of papillary carcinoma.
      DNA is obtained by laser microdissection from WNF and WONF areas of each case.
      Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by
      direct sequencing. In 11 cases, reverse transcription PCR was performed for the
      presence of PAX8-PPARgamma and RET/PTC1-3 gene rearrangements. Point mutation for
      NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed
      at least one mutation; two cases (13 %) revealed the same mutation in both WNF
      and WONF areas, while in the rest only WNF areas were mutated. None of the
      studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case
      PAX8-PPARgamma gene rearrangement was found. Six cases (38 %) showed NRAS codon
      61 mutation, involving only WNF areas in five cases and both WNF and WONF areas
      in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen
      colloidal nodules were also wild type for NRAS codon 61. Our findings suggest
      that NRAS codon 61 point mutations and PAX8-PPARgamma gene rearrangement play a
      role in the FVPTC pathogenesis and may be established before the
      morphological/phenotypical features fully develop.

PMID- 24277233
TI  - Let's engage the patient within us: a personal perspective on patient engagement.

PMID- 24277234
TI  - Time to health-related quality of life score deterioration as a modality of
      longitudinal analysis for health-related quality of life studies in oncology: do
      we need RECIST for quality of life to achieve standardization?
AB  - PURPOSE: Longitudinal analysis of health-related quality of life (HRQoL) remains
      unstandardized and compromises comparison of results between trials. In oncology,
      despite available statistical approaches, results are poorly used to change
      standards of care, mainly due to lack of standardization and the ability to
      propose clinical meaningful results. In this context, the time to deterioration
      (TTD) has been proposed as a modality of longitudinal HRQoL analysis for cancer
      patients. As for tumor response and progression, we propose to develop RECIST
      criteria for HRQoL. METHODS: Several definitions of TTD are investigated in this
      paper. We applied this approach in early breast cancer and metastatic pancreatic
      cancer with a 5-point minimal clinically important difference. In breast cancer,
      TTD was defined as compared to the baseline score or to the best previous score.
      In pancreatic cancer (arm 1: gemcitabine with FOLFIRI.3, arm 2: gemcitabine
      alone), the time until definitive deterioration (TUDD) was investigated with or
      without death as event. RESULTS: In the breast cancer study, 381 women were
      included. The median TTD was influenced by the choice of the reference score. In
      pancreatic cancer study, 98 patients were enrolled. Patients in Arm 1 presented
      longer TUDD than those in Arm 2 for most of HRQoL scores. Results of TUDD were
      slightly different according to the definition of deterioration applied.
      CONCLUSION: Currently, the international ARCAD group supports the idea of
      developing RECIST for HRQoL in pancreatic and colorectal cancer with liver
      metastasis, with a view to using HRQoL as a co-primary endpoint along with a
      tumor parameter.

PMID- 24277235
TI  - Multimodal treatment of locally advanced esophageal adenocarcinoma: which regimen
      should we choose? Outcome analysis of perioperative chemotherapy versus
      neoadjuvant chemoradiation in 105 patients.
AB  - BACKGROUND: The study was done to compare treatment and long-term outcomes of
      neoadjuvant chemoradiation (neoCRT) and perioperative chemotherapy (periCTX) in
      patients with surgically treated esophageal adenocarcinoma. METHODS: An analysis
      of 105 patients with esophageal adenocarcinoma undergoing neoCRT (n = 58) or
      periCTX (n = 47) and esophagectomy between 2000 and 2012 was carried out.
      RESULTS: The overall median survival was 5.97 years. Postoperative morbidity and
      in-hospital mortality occurred in 74%/7% of the patients the neoCRT group and in
      53%/0% of the patients in the periCTX group (P = 0.03/P = 0.08). Total or
      subtotal histological tumor response after neoadjuvant treatment and
      esophagectomy was found in 59% after neoCRT and 30% after periCTX (P < 0.01).
      Three- and five-year survival rates were 52%/45% for neoCRT and 68%/63% for
      periCTX (P = 0.05). PeriCTX was identified as an independent predictor of
      survival (RR2.6; 95% CI 1.3-5.1; P < 0.01). CONCLUSION: A higher rate of
      histologic response to neoCRT compared to histologic response following the
      preoperative cycles of periCTX does not translate to a benefit in overall
      survival. PeriCTX offers a decreased incidence of treatment-related morbidity and
      mortality and at least equal results in terms of survival compared to neoCRT in
      patients with locally advanced esophageal adenocarcinoma.

PMID- 24277236
TI  - Host plant utilization and iridoid glycoside sequestration byEuphydryas anicia
      (Lepidoptera: Nymphalidae).
AB  - The iridoid glycoside content of individual adultEuphydryas anicia butterflies
      from two Colorado populations was quantitatively determined. At one site (Red
      Hill), larval host plants wereCastilleja integra andBesseya plantaginea, while at
      the other site (Cumberland Pass) a single host plant,B. alpina, was used. At Red
      Hill, macfadienoside and catalpol were sequestered, while at Cumberland Pass,
      catalpol and aucubin were sequestered. Artificial diet studies showed that larvae
      hydrolyzed a major iridoid ofB. plantaginea, 6-isovanilIylcatalpol, to catalpol
      (which was sequestered) and isovanillic acid (which was excreted). Large year-to
      year and individual variation in butterfly iridoid content was established as was
      a female-male difference in macfadienoside vs. catalpol content. Larval host
      plant distributions and numbers were determined at Red Hill for two years and
      compared with changes in butterfly populations and sequestered iridoids. 

PMID- 24277237
TI  - Aggregation pheromone of square-necked grain beetle,Cathartus quadricollis
      (Guer.).
AB  - When feeding on rolled oats, male square-necked grain beetles,Cathartus
      quadricollis (Guer.), produced the aggregation pheromone (3R,6E)-7-methyl-6-nonen
      3-yl acetate, for which the trival name "quadrilure" is proposed. The pheromone
      was highly attractive to both sexes in a two-choice, pitfall olfactometer
      modified to retain responding beetles by placing a food stimulus (an oat flake)
      in the glass vials containing the experimental and control stimuli. TheS
      enantiomer of the pheromone was inactive. Males also produced small amounts of
      (E)-7-methyl-6-nonen-3-one, (E)-7-methyl-6-nonen-3-ol, and (6E)-7-methyl-3-propyl
      2,6-nonadienyl acetate, but these compounds were inactive in the laboratory
      bioassay. Segregated males and females both produced (R)-(-)-1-octen-3-ol, which
      by itself was repellent to both sexes but did not diminish beetle response to the
      aggregation pheromone. 

PMID- 24277238
TI  - Lipid cues for seed-carrying by ants inHepatica americana.
AB  - We investigated the chemical basis for ants carrying the seeds ofHepatica
      americana, an ant-dispersed plant of eastern North America. A laboratory bioassay
      of seed and elaiosome extracts was based on the distance test items were carried
      byPogonomyrmex rugosus. Ants responded equally to isolated elaiosomes and to the
      diglyceride fraction. Diolein was a major component of the diglyceride fraction,
      which is consistent with a finding that 1,2-diolein releases seed-carrying
      byAphaenogaster rudis. Ants' response to the free fatty acid fraction was less
      intense. Gas chromatography of the fatty acid fraction indicated that oleic acid
      was a primary component, and oleic acid is known to elicit necrophoric behavior.
      No evidence supports an earlier suggestion that ricinoleic acid stimulates seed
      carrying behavior. Ants failed to respond to seeds from which elaiosomes were
      removed. 

PMID- 24277239
TI  - Chemotaxonomic implications of the venom chemistry of someMonomorium
      "antarcticum" populations.
AB  - A comparative analysis of the venom alkaloids produced by ants in the
      genusMonomorium (= Chelaner) collected on North Island and South Island, New
      Zealand, has been undertaken. All of the ants producetrans-2, 5
      dialkylpyrrolidines along with 3,5-dialkylpyrrolizidines. The structures and
      sterochemistry of the novel alkaloidstrans-2-butyl-5-(8-nonenyl) pyrrolidine,
      (5E,8Z)-3,5-di(5-hexenyl)pyrrolizidine, and (5Z,8E)-3-methyl-5-(8
      nonenyl)pyrrolizidine were established by unambiguous synthesis. The geographic
      distribution and the chemotaxonomic significance of the alkaloids produced by
      these ants are discussed. 

PMID- 24277240
TI  - Cyanogenic glucosides as defense compounds : A review of the evidence.

PMID- 24277241
TI  - What is chemical ecology? : A reply.

PMID- 24277243
TI  - Editorial.

PMID- 24277242
TI  - Climate change implications of shifting forest management strategy in a boreal
      forest ecosystem of Norway.
AB  - Empirical models alongside remotely sensed and station measured meteorological
      observations are employed to investigate both the local and global direct climate
      change impacts of alternative forest management strategies within a boreal
      ecosystem of eastern Norway. Stand-level analysis is firstly executed to
      attribute differences in daily, seasonal, and annual mean surface temperatures to
      differences in surface intrinsic biophysical properties across conifer,
      deciduous, and clear-cut sites. Relative to a conifer site, a slight local
      cooling of -0.13  degrees C at a deciduous site and -0.25  degrees C at a clear
      cut site were observed over a 6-year period, which were mostly attributed to a
      higher albedo throughout the year. When monthly mean albedo trajectories over the
      entire managed forest landscape were taken into consideration, we found that
      strategies promoting natural regeneration of coniferous sites with native
      deciduous species led to substantial global direct climate cooling benefits
      relative to those maintaining current silviculture regimes - despite predicted
      long-term regional warming feedbacks and a reduced albedo in spring and autumn
      months. The magnitude and duration of the cooling benefit depended largely on
      whether management strategies jointly promoted an enhanced material supply over
      business-as-usual levels. Expressed in terms of an equivalent CO2 emission pulse
      at the start of the simulation, the net climate response at the end of the 21st
      century spanned -8 to -159 Tg-CO2-eq., depending on whether near-term harvest
      levels increased or followed current trends, respectively. This magnitude equates
      to approximately -20 to -300% of Norway's annual domestic (production) emission
      impact. Our analysis supports the assertion that a carbon-only focus in the
      design and implementation of forest management policy in boreal and other
      climatically similar regions can be counterproductive - and at best - suboptimal
      if boreal forests are to be used as a tool to mitigate global warming.

PMID- 24277244
TI  - Drug concentration, binding, and effect in vivo.
AB  - It is an axiom of pharmacodynamics that drug effects are determined by drug
      concentration at the site of action. The link between concentration and effect
      can often be described by empirical models, but the ability to measure binding to
      the target tissue permits a more detailed description. The action and interaction
      of drugs at identifiable receptor sites can then be predicted from a knowledge of
      their binding properties and the law of mass action. The time course of drug
      effect is determined not only by drug disposition reflected in the blood
      circulation but also by the equilibration rate between blood and the effect site,
      and the steps linking the direct actions of the drug to their expression as an
      observable drug effect. Models encompassing these phenomena have been developed
      and have been applied in many situations to describe the kinetics of
      pharmacological response. 

PMID- 24277245
TI  - Nephelometric immunoassay for therapeutic drug level monitoring.
AB  - Nephelometric immunoassay for the determination of drug levels in blood is based
      on the inhibition of immunoprecipitation by a hapten (drug). It represents a
      homogeneous method that does not require any separation steps nor radioisotopes.
      Precipitation in an aqueous solution can be quantitated by nephelometry
      (scattered light measurement) or turbidmetry (traversed light measurement).
      Advantages over other drug assay methods include its simplicity, speed and low
      cost. Only two reagents are added, and the subsequent reaction can be monitored
      optically with the potential for full automation. The reaction is usually
      completed in less than 15 minutes. The two reagents, anti-drug antibody and
      polyhaptenic antigen, can be easily prepared and are highly stable. Therefore,
      precipitation inhibition immunoassays and in particular nephelometric
      immunoassays are being commercially developed for routine therapeutic monitoring
      of drugs such as anticonvulsant drugs, aminoglycoside antibiotics and
      theophylline. The specificity is high, though depending on the cross-reactivity
      of the anti-drug antibody as is the case with other immunoassays. The sensitivity
      depends on a variety of factors such as antibody-hapten affinity, detection mode
      of the precipitation, and intrinsic turbidity of the test sample. But the
      sensitivity is sufficiently high for serum drug concentration greater than 1
      ug/ml when less than 10 ul of serum are used. Variations of this assay technique
      include rate analysis for precipitate formation instead of endpoint analysis.
      Agglutination-, or particle aggregation-inhibition immunoassay is also a useful
      and more sensitive method. Finally, use of monoclonal antibodies can serve to
      enhance the specificity of nephelometric immunoassay of drugs. 

PMID- 24277246
TI  - Studies on the mechanism of fluoropyrimidine cytotoxicity in l1210 cells:
      correlation with inhibition of thymidylate synthetase but not with incorporation
      into RNA.
AB  - The effects of 5-fluorouracil (FUra), 5-fluorouridine (FUrd), and 5-fluoro-2'
      deoxyuridine (FdUrd) on L1210 cells were examined in an effort to determine
      whether the cytotoxicity of these fluoropyrimidines is more closely associated
      with incorporation of FUra residues into RNA or inhibition of thymidylate (dTMP)
      synthetase (5,10-methylenetetrahydrofolate: deoxyuridylate C-methyl-transferase,
      EC 2.1.2.45) by 5-fluoro-2'-deoxyuridylate (FdUMP). In different batches of cells
      exposed to equitoxic (LD50) doses of these drugs for 48 hr, the levels of free
      FdUMP, dUMP, and free dTMP synthetase were found to be very similar. However, the
      number of FUra residues incorporated into total cellular RNA were in the
      approximate ratio of 1:10:100 in cells treated with FdUrd, FUrd, and FUra,
      respectively. Although these results are consistent with a common DNA-directed
      mechanism of toxicity, thymidine (dThd), which should circumvent dTMP synthetase
      inhibition, did not rescue the cells from the effects of FUra. However, uridine
      (Urd), which should compete with FUra for incorporation into RNA, had no effect
      on the toxicity of FUra either. Urd at 10(-5) M did not decrease the amount of
      incorporation of 10(-7)M [(3)H]FUra into total RNA, but a limited fractionation
      of polysomal RNA showed about a 4-fold decrease of incorporation of FUra into
      mRNA in the presence of Urd. Urd and dThd did effectively decrease the
      cytotoxicity of FUrd and FdUrd, respectively. These observations suggest that
      cell rescue experiments may not be reliable indicators of the mechanism of
      cytotoxicity of antimetabolites with complex mechanisms of action. 

PMID- 24277247
TI  - An efficient in vitro assay for acetylcholinesterase reactivators using
      immobilized enzyme.
AB  - A new and efficient in vitro assay for evaluating reactivators of organophosphate
      inhibited acetylcholinesterase has been developed. Low density polyethylene beads
      (4 mm) were func-tionalized to terminal aldehydes and used to immobilize
      acetylcholinesterase (AChE, Electrophorus electricus, E.G. 3.1.1.7) via a stable
      Schiff base link. AChE activity in columns containing immobilized enzyme could be
      continuously monitored spectrophotometrically in a closed loop flow system using
      acetylthiocholine and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Immobilized
      enzyme exhibited good esterase activity (0.5 units/bead), which could be retained
      on storage at -16 degrees C for four months. The kinetics for substrate
      hydrolysis were flow-rate dependent below substrate saturation levels. This
      system allowed for independent inhibition and reactivation of the enzyme.
      Immobilized enzyme could be inhibited with diisopropylfluorophosphate (DFP) and
      20-90% of original activity restored with several oximes in less than 20 minutes.
      The extent of reactivation was dependent on the concentration of the
      reactivators. This system has advantages over previously reported procedures,
      because hydrolysis of substrate due to reactivator is minimized and inhibitor
      reactivator interactions are eliminated, subsequently minimizing the need to
      correct experimental results. 

PMID- 24277248
TI  - Soft Drugs VI. The Application of the Inactive Metabolite Approach for Design of
      Soft beta-Blockers1?2.
AB  - The "inactive metabolite approach" was used to design beta-blockers. The acidic
      inactive metabolite of metoprolol [4-(2-hydroxy-3-isopropylamino)
      propoxyphenylacetic acid] was used as the lead compound. Its esters (alkyl and
      cycloalkyl) were found active in vivo while reverting quantitatively to the same
      inactive metabolite in plasma. The cyclohexyl ester showed the best activity,
      which was cardioselective, similar to the parent compound metoprolol. Although
      most esters had a plasma half-life of approximately 1 min, their activity
      (antagonism of isoproterenol induced increase in heart rate) following
      intravenous administration lasted 45-90 minutes, and the maximum beta-blockade
      was observed at 45-60 minutes in both rats and dogs. 

PMID- 24277249
TI  - Irreversible Binding of Norethisterone to Human Serum Protein Induced by UV-B
      Light.
AB  - In as much as oral contraceptive ingestion has been associated with photoallergic
      effects, the irreversible binding of 4-(14)C-norethisterone to proteins catalyzed
      by UV-B light (290-320 nm) was investigated. Irreversible binding to a human
      plasma protein mixture and to albumin of the radiolabeled progestogen was linear
      for 40min, when mixtures of protein and steroid were irradiated with UV-B light.
      Approximately 16 % of the radiolabel was irreversibly bound under the conditions
      of the assay. Irreversible binding also occurred, when proteins were added
      several hours after irradiation. Preliminary experiments in rats administered 4
      (14)C-norethisterone also indicate the formation in skin and liver of
      irreversibly bound adducts under photoreactive conditions. Such reactions may in
      part be responsible for some of the side-effects associated with oral
      contraceptive use. 

PMID- 24277250
TI  - Site specific rectal drug administration in man with an osmotic system: influence
      on "first-pass" elimination of lidocaine.
AB  - Lidocaine was administered to healthy volunteers at different sites in the
      rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were
      measured in plasma with a newly developed gas chromatographic method. Lidocaine
      was given rectally by means of an osmotic system (Osmet((r))) which delivered 25
      mg/h at zero-order rate. In a pilot experiment in two subjects it was shown that
      lidocaine administration close to the anus for 5 h resulted in higher lidocaine
      plasma levels as compared to administration at 15 cm from the anus. Six other
      subjects participated in three separate experiments, in which lidocaine was
      administered rectally close to the anus and at 7.5 and 15 cm from the anus. A
      zero-order infusion plasma level profile was found for both the parent compound
      and its metabolite. The MEGX/lidocaine plasma concentration ratio was calculated
      for all experiments. After administration most proximal to the anus the mean
      metabolite/parent drug concentration ratio was significantly less than that
      obtained after administration at 15 cm from the anus, whereas at approximately
      7.5 cm from the anus the values were in-between. Comparison of the AUC
      lidocaine/AUC MEGX ratios gave similar results; the highest value, 3.2 +/- 1.3
      (mean +/- S. D.), was found after administration close to the anus, while at 15
      cm from the anus the ratio was 1.6 +/- 0.3 (p < 0.01). The terminal elimination
      half-lives of lidocaine and MEGX did not differ for the three sites of
      administration, and the mean values were 110 and 180 min respectively. The
      results of this study demonstrate that the site of drug administration in the
      human rectum determines the degree of hepatic "first-pass" elimination of high
      clearance drugs. Maximal avoidance of presystemic elimination is achieved when
      administration takes place close to the anus. 

PMID- 24277251
TI  - Effect of thyrotropin-releasing hormone on lipoxygenase-induced hypotension in
      the unanesthetized Guinea pig.
AB  - Soybean lipoxygenase, an enzyme which catalyzes the formation of the vasoactive
      lipid 15-hydroperoxy eicosatetraenoic acid (15-HPETE) from arachidonic acid, was
      administered to unanesthetized guinea pigs previously prepared with indwelling
      vascular cannulae for continuous cardiovascular monitoring. Administration of
      this enzyme (150 mg/kg IV) resulted in profound hypotension in this model, but no
      cardiovascular change was observed after administration of equal weight or
      equimolar amounts of another protein (ovalbumin). The lipoxygenase-induced
      hypotension, moreover, was promptly reversed by the peptide thyrotropin-releasing
      hormone (TRH) (2 mg/kg IV) but not by the opiate receptor antagonist naloxone (2
      mg/kg IV). This TRH-naloxone dissociation was comparable to that previously
      observed in hypotension produced by leukotriene D4 (LTD4), platelet-activating
      factor (PAF), or antigen-induced anaphylaxis in the same species. Thus, although
      its properties as a "physiologic" opiate antagonist led to the early trials of
      TRH in endotoxic, hypovolemic and spinal shock, it is now apparent that TRH
      reverses several other forms of experimental shock, including that caused by
      lipoxygenase, through non-endorphin-related mechanism. 

PMID- 24277252
TI  - Importance of structural free space to the solvent power of water.
AB  - The contribution of structural free space to the solvent power of water was
      examined by a systematic modification of the geometric factor. Gaps and holes,
      available to foreign molecule occupation, are thought to be filled at low
      concentrations (max. 1 %) of aliphatic alcohols. The effect upon solvency reached
      approximately 10%, which suggests that spatial parameters affect solvent power.
      The results demonstrate the importance of solvent purity in the dissolution
      process. 

PMID- 24277253
TI  - Lack of tobramycin distribution into saliva.

PMID- 24277254
TI  - Increased prevalence of inherited neuromuscular disorders due to endogamy in
      Northeast Brazil: the need of community genetics services.
AB  - The aim of this study was to investigate the prevalence of inherited
      neuromuscular disorders (NMDs) in eight communities in Northeast (NE) Brazil in
      which there was an elevated rate of inbreeding. A cross-sectional epidemiological
      study, using the key informant (KI) approach, was performed to estimate the
      prevalence of NMD among the 48,499 individuals living in these eight communities,
      located in the backlands of the Paraiba State. Twenty-seven individuals fulfilled
      the diagnostic criteria for inherited NMD, which means that 1 out of 1,796
      inhabitants of this highly consanguineous population was affected by NMD. This is
      twofold higher than that observed in previous studies in general population and
      was probably due to a combination of genetic drift and inbreeding. Public
      policies should be implemented to offer genetics services in high-risk
      communities. 

PMID- 24277255
TI  - A new agenda for health in Europe.

PMID- 24277257
TI  - Dental caries and oral health-related factors in a sample of Greek preschool
      children.
AB  - AIM: To assess the caries prevalence and some background factors in 3- to 5.5
      year-old children in the municipality of Thessaloniki, Greece. METHODS: One
      calibrated examiner examined the children of all municipal day care centres for
      dmfs, existence of visible dental plaque and presence of black stain. Examination
      was made on site using disposable dental mirrors. Questionnaires were given to
      parents for assessing socio-economic status, oral hygiene habits (brushing
      frequency, toothpaste use) and sucking/feeding at sleep habits (nursing bottle,
      its content and pacifier use). RESULTS: Out of a total of 950 children, both
      clinical examination and questionnaire data were available for 804 children. The
      overall mean dmfs was 1.3 (SD = 3.8). The caries prevalence was 22.6 %, while the
      presence of black stain was evident in 2.4 % of the children. Intra-examiner
      agreement was estimated with Kendall's tau b = 0.99. A generalised linear model
      used to fit a Poisson regression for the analysis of count outcome data (dmfs)
      and logistic regression was used for binary outcome data (presence or absence of
      visible dental plaque). Statistically significant association was found between
      dmfs and the presence of visible dental plaque. The country of origin and
      education status of the parents were found to be significant factors for dmfs.
      The presence of black stain was negatively correlated with dmfs. CONCLUSIONS: The
      mean dmfs was lower than earlier Greek data. Country of origin, education status
      of the parents and visible dental plaque seemed to be important caries risk
      factors, while the presence of black stain was a strong caries resistance
      predictor.

PMID- 24277258
TI  - Who shall be served? Issues in screening for emotional and behavioral problems in
      school.
AB  - The major issues involved in the design and implementation of effective school
      screening programs are addressed, using data from a longitudinal study following
      over 500 children from preschool through third grade. The article identifies
      early characteristics of children that are related to later behavioral and
      emotional problems, assesses the accuracy of a comprehensive screening procedure
      for identifying such problems, and compares two models using preschool and
      kindergarten data. Characteristics of children missed by the models are
      presented, and labeling issues are addressed. Implications for future screening
      efforts, policy, and research are discussed. 

PMID- 24277259
TI  - Partnership for mental health promotion.
AB  - Given the conceptual shift from a focus on primary prevention to mental health
      promotion, this article suggests that mental health promotion activities not be
      conducted in mental health agencies but in those human service systems involved
      with the normal processes of living. The major thesis of this article is that a
      partnership between the mental health system and the other human service agencies
      is essential. This requires a clear delineation and differentiation of roles to
      be performed by the mental health professional. 

PMID- 24277260
TI  - Prevention and early intervention: An operational model.
AB  - A program is described that focuses on significant involvement of parents in the
      delivery of services to their own young children with behavior problems or
      handicaps. The goal of the program is to provide intervention as early as
      possible in the child's life by training parents as agents of change either
      before the problem occurs or in its early stages. Professional staff design and
      adapt change strategies for the parents to apply directly in the clinic and in
      "real life" circumstances at home. Trained and experiencd parents then become the
      foundation of the program. They train new parents entering the system and utilize
      the professional staff as resources. This model of using parents is discussed in
      relation to current funding trends and the need for cost-effective systems of
      service delivery. 

PMID- 24277261
TI  - The short-term effect of a national prevention model on student drug abuse.
AB  - This article presents the results of a short-term evaluation of a national drug
      abuse prevention model entitled the Ombudsman Program (OP). The OP was approved
      as a national model by the U.S. Department of Education in 1979, and is currently
      being disseminated nationwide via the National Diffusion Network (NDN). This
      outcome evaluation research is based on the data generated by the most recent
      replication of the OP in spring semester 1981 in Charlotte. A quasi-experimental
      design was used, with 29 students in the treatment group and 30 students in the
      control group, all at the sixth grade level. Using the "high-risk" Student
      Attitudinal Inventory (SAI), the following results were obtained: (1) at the
      conclusion of the OP, a larger proportion of students in the treatment group had
      favorable attitudes toward their regular school teachers than was the case in the
      control group; (2) when the students' appraisal of the importance of the program
      content of the OP is compared to the regular school program, there does not seem
      to be a significant difference between the two; (3) between the pre- and post
      tests, there were positive attitudinal improvements in five out of seven "high
      risk" factors that are closely related to the frequency of student drug
      involvement; and (4) the magnitude of these changes, however, is minimal in
      general and statistically nonsignificant. Finally, a number of recommendations
      applicable not only to the OP but to other drug education/prevention programs are
      presented on the basis of the data generated from numerous replications of the OP
      between 1977 and 1981. 

PMID- 24277263
TI  - Primary prevention program clearinghouse psychology department-Dewey hall
      University of Vermont, Burlington, VT 05405.

PMID- 24277262
TI  - Early intervention with the unemployed: Employment transition program of the
      university of Michigan.

PMID- 24277264
TI  - Coming to peace with protein complexes? 5th CAPRI evaluation meeting, April 17
      19th 2013--Utrecht.

PMID- 24277265
TI  - The contribution of radiology to the study of the past: the Venetian experience-
      the mummies of the Fontego dei Turchi.

PMID- 24277266
TI  - A train-related fatality--old dilemmas: accident, suicide, or homicide? Premortem
      or postmortem decapitation?

PMID- 24277267
TI  - The value of sub-stages and thin slices for the assessment of the medial
      clavicular epiphysis: a prospective multi-center CT study.
AB  - The clavicle plays an important role for forensic age estimation in living
      individuals, particularly with regard to the age of majority. The present
      prospective study aims to evaluate the age-dependent ossification process of the
      medial clavicular epiphysis in order to establish the clavicular sub-stages
      introduced in 2010 as well as the advantages and possibilities of thin-slice
      computed tomography (CT). For this purpose, 0.6 mm thin-slice CT scans of
      sternoclavicular joints of 572 bodies aged between 10 and 40 years were evaluated
      by means of two complementary classification systems: a five-stage system and a
      sub-staging system for the main stages 2 and 3. Assessment was possible in 493
      cases. The results for stages 4 and 5 are in line with previous studies that
      found the ages of 21 years and 26 years, respectively, as minimum ages for these
      stages. Sub-stage 3c was first found at the age of 19 years in both sexes,
      thereby corroborating the value of this sub-stage as to statements about the age
      of majority. In comparison to other CT studies, stage 3a was first observed ~1
      year earlier (16.4 years in males and 15.5 years in females). Stage 2c only
      occurred in 3 cases. In conclusion, the data corroborate the significance of
      diagnosing sub-stages as well as the value of thin-slice CT. For forensic
      practice, the concomitant and complementary use of both classification systems
      applied in this study can be recommended. 

PMID- 24277268
TI  - "Crow's feet" as an indication of a vital reaction in a gunshot victim.

PMID- 24277269
TI  - Adolescent pubertal status and affective family relationships: A multivariate
      assessment.
AB  - This research attempted to more adequately dimensionalize the study of affective
      family relations during adolescent pubertal maturation by employing a
      multivariate approach. Fifty-one families responded to an assessment battery
      consisting of a series of questionnaires designed to measure affective relations
      between parents and their adolescent children. Families were classified into
      prepubertal, transpubertal, or postpubertal groups according to their modal
      response on pubertal status criteria. A stepwise discriminant analysis was
      performed to identify measures that maximize between groups differences. Based on
      this analysis, a correct classification rate of 70% was achieved for all
      families. The two significant discriminant functions that emerged indicate that
      differences in family relationships are due to the transformation of mother
      adolescent and father-adolescent relations. The pattern of results replicate
      those of other researchers and provide elaborations concerning the affective
      nature of family relations during adolescence. 

PMID- 24277270
TI  - The extent and function of parental attachment among first-year college students.
AB  - The extent and function of the parent-child bond, conceptualized according to
      Ainsworth's (M.D.S. Ainsworth, M. C. Blehar, E. Walters, and S. Wally
      [1978],Patterns of Attachment: A Psychological Study of the Strange Situation,
      Erlbaum Associates, Hillsdale, NJ) model of attachment, was explored for a group
      of first-year college students (N=173) at a selective, prestigious, northeastern
      university. Overall, students' descriptions of their parental relationships were
      positive and resembled Ainsworth's secure attachment type. Most students viewed
      their parents as a secure base, encouraging independence and remaining available
      as a source of support when needed. Furthermore, students indicated that they
      sought parental help more than a moderate amount in situations of stress. For
      female students, close parental relationships were found to be positively
      associated with self-reports of assertion. 

PMID- 24277271
TI  - Long-term effects of parental divorce on young adult male crime.
AB  - The purpose of this study was to explore the long-term effects of parental
      divorce on young adult male crime from a longitudinal perspective. Four hundred
      and twenty-three males were randomly selected from a Danish birth cohort. Results
      of analyses of variance showed an initial significant relationship between
      divorce and young adult crime. However, the effects of divorce disappeared when
      further path analysis controlled for the effects of social class and father's
      criminality. In addition, time of divorce did not have an effect on later
      criminal behavior. 

PMID- 24277272
TI  - The adolescent as mother: Early risk identification.
AB  - Adjustment to parenting is a difficult process for the adolescent. This research
      attempted to identify easy-to-use maternal postpartum screening dimensions to
      predict two-month adjustment among 28 primipara adolescents. The results suggest
      several predictors of adjustment: initial parenting attitudes, preparation for
      parenting including involvement in instruction as well as specific knowledge
      areas, infant holding style, and aspects of social functioning. Postpartum risk
      screening may be a feasible way to identify intervention needs. Early screening
      would encourage early involvement in preventive programs. It would also provide a
      framework for evaluation and improvement of services to young mothers. 

PMID- 24277273
TI  - Self-doubt in late childhood and early adolescence.
AB  - This study examined the development of self-doubt in late childhood and early
      adolescence. Self-doubt was operationalized as the self-reported degree of
      uncertainty about the self's attributes. According to social-cognitive theory,
      self-doubt should decrease as social norms for self-evaluation are acquired
      through role-taking development. Seventy-five children at three ages-10, 13, and
      16-were administered Selman's role-taking interview, a measure of social
      desirability, and a multidomain measure of self-doubt. Consistent with the social
      cognitive model, self-doubt decreased with age during early adolescence. Role
      taking ability increased with age. However, advances in role taking were not
      necessary for the resolution of self-doubt, nor could the decline in self-doubt
      be attributed to the tendency of older adolescents to conceal socially
      undesirable feelings. The findings support the view that adolescence is a period
      of consolidation for self-evaluations. 

PMID- 24277274
TI  - School aptitude and achievement in children of adolescent mothers.
AB  - The effects of adolescent childbearing and parenting on the academic aptitude and
      achievement of fourth-grade children were examined by comparing children of
      mothers in three age groups at the birth of the first child: 15-17 years, 18-19
      years, and 20-24 years. The data are from a longitudinal study of a community
      population of schoolchildren. Outcome measures were tests of cognitive skills at
      preschool screening, parent and teacher ratings of school performance at grade 3,
      and tests of aptitude and achievement at grade 4. After controlling for gender,
      birth order, family structure, and maternal education, results indicated that
      children of adolescent mothers, whether early or late adolescence, were generally
      not different from children of mothers in their early 20s with respect to
      academic ability and performance. Maternal education had a far greater impact on
      the outcome measures than did maternal age. 

PMID- 24277276
TI  - Increasing ocean temperatures reduce activity patterns of a large commercially
      important coral reef fish.
AB  - Large-bodied fish are critical for sustaining coral reef fisheries, but little is
      known about the vulnerability of these fish to global warming. This study
      examined the effects of elevated temperatures on the movement and activity
      patterns of the common coral trout Plectropomus leopardus (Serranidae), which is
      an important fishery species in tropical Australia and throughout the Indo West
      Pacific. Adult fish were collected from two locations on Australia's Great
      Barrier Reef (23 degrees S and 14 degrees S) and maintained at one of four
      temperatures (24, 27, 30, 33  degrees C). Following >4 weeks acclimation, the
      spontaneous swimming speeds and activity patterns of individuals were recorded
      over a period of 12 days. At 24-27  degrees C, spontaneous swimming speeds of
      common coral trout were 0.43-0.45 body lengths per second (bls(-1)), but dropped
      sharply to 0.29 bls(-1) at 30  degrees C and 0.25 bls(-1) at 33  degrees C.
      Concurrently, individuals spent 9.3-10.6% of their time resting motionless on the
      bottom at 24-27  degrees C, but this behaviour increased to 14.0% at 30  degrees
      C and 20.0% of the time at 33  degrees C (mean +/- SE). The impact of temperature
      was greatest for smaller individuals (<45 cm TL), showing significant changes to
      swimming speeds across every temperature tested, while medium (45-55 cm TL) and
      large individuals (>55 cm TL) were first affected by 30  degrees C and 33 
      degrees C, respectively. Importantly, there was some indication that populations
      can adapt to elevated temperature if presented with adequate time, as the high
      latitude population decreased significantly in swimming speeds at both 30 
      degrees C and 33  degrees C, while the low-latitude population only showed
      significant reductions at 33  degrees C. Given that movement and activity
      patterns of large mobile species are directly related to prey encounter rates,
      ability to capture prey and avoid predators, any reductions in activity patterns
      are likely to reduce overall foraging and energy intake, limit the energy
      available for growth and reproduction, and affect the fitness and survival of
      individuals and populations.

PMID- 24277275
TI  - Quantitative histological analysis and ultrastructure of the aging human testis.
AB  - PURPOSE: To quantitatively assess the histological and ultrastructural changes
      resulting from aging in the human testis. METHODS: Age-related histological and
      ultrastructural changes were evaluated using light microscopy, transmission
      electron microscopy (TEM) and immunohistochemistry on 41 testicular samples
      obtained from elderly men and, respectively, assigned to group A (n = 20), 54-69
      years old or group B (n = 21), 70-89 years old. Testicular samples derived from
      17 young men were used for control. RESULTS: The numbers of Sertoli cells in the
      aged groups were significantly lower than that in the controls (p < 0.05). With
      the exception of the Sertoli cell ratios (germ cells/Sertoli cells) of
      spermatogonia and primary spermatocytes, results showed lower levels of the
      Sertoli cell ratios of round spermatids and elongated spermatids in the elderly
      men compared with the young men (p < 0.05). A similar degenerative pattern of the
      organelles was shown in germ cells and Sertoli cells in the aging testes under
      TEM. Immunohistochemistry revealed an increased apoptosis index (AI) (0.81 +/-
      0.13) accompanied by a decreased proliferation index (PI) (30.08 +/- 4.86) in the
      group B (p < 0.05), while both AI and PI were similar between the group A (0.54
      +/- 0.06; 36.38 +/- 7.38) and the controls (0.50 +/- 0.15; 40.55 +/- 7.92) (p >
      0.05). CONCLUSIONS: Aging has negative influence on testicular morphology and
      spermatogenesis, and the failure of spermatogenic cell development is evident
      from the spermatid level.

PMID- 24277277
TI  - TIME FOR COFFEE controls root meristem size by changes in auxin accumulation in
      Arabidopsis.
AB  - Roots play important roles in plant survival and productivity as they not only
      anchor the plants in the soil but are also the primary organ for the uptake of
      nutrients from the outside. The growth and development of roots depend on the
      specification and maintenance of the root meristem. Here, we report a previously
      unknown role of TIME FOR COFFEE (TIC) in controlling root meristem size in
      Arabidopsis. The results showed that loss of function of TIC reduced root
      meristem length and cell number by decreasing the competence of meristematic
      cells to divide. This was due to the repressed expression of PIN genes for
      decreased acropetal auxin transport in tic-2, leading to low auxin accumulation
      in the roots responsible for reduced root meristem, which was verified by
      exogenous application of indole-3-acetic acid. Downregulated expression of
      PLETHORA1 (PLT1) and PLT2, key transcription factors in mediating the patterning
      of the root stem cell niche, was also assayed in tic-2. Similar results were
      obtained with tic-2 and wild-type plants at either dawn or dusk. We also
      suggested that the MYC2-mediated jasmonic acid signalling pathway may not be
      involved in the regulation of TIC in controlling the root meristem. Taken
      together, these results suggest that TIC functions in an auxin-PLTs loop for
      maintenance of post-embryonic root meristem. 

PMID- 24277278
TI  - MYB10 plays a major role in the regulation of flavonoid/phenylpropanoid
      metabolism during ripening of Fragaria x ananassa fruits.
AB  - This work characterized the role of the R2R3-MYB10 transcription factor (TF) in
      strawberry fruit ripening. The expression of this TF takes place mainly in the
      fruit receptacle and is repressed by auxins and activated by abscisic acid (ABA),
      in parallel to the ripening process. Anthocyanin was not produced when FaMYB10
      expression was transiently silenced in fruit receptacles. An increase in FaMYB10
      expression was observed in water-stressed fruits, which was accompanied by an
      increase in both ABA and anthocyanin content. High-throughput transcriptomic
      analyses performed in fruits with downregulated FaMYB10 expression indicated that
      this TF regulates the expression of most of the Early-regulated Biosynthesis
      Genes (EBGs) and the Late-regulated Biosynthesis Genes (LBGs) genes involved in
      anthocyanin production in ripened fruit receptacles. Besides, the expression of
      FaMYB10 was not regulated by FaMYB1 and vice versa. Taken together, all these
      data clearly indicate that the Fragaria * ananassa MYB10 TF plays a general
      regulatory role in the flavonoid/phenylpropanoid pathway during the ripening of
      strawberry. 

PMID- 24277279
TI  - Specification of floral organs in Arabidopsis.
AB  - Floral organs are specified by the activities of a small group of transcriptional
      regulators, the floral organ identity factors. Extensive genetic and molecular
      analyses have shown that these proteins act as master regulators of flower
      development, and function not only in organ identity determination but also
      during organ morphogenesis. Although it is now well established that these
      transcription factors act in higher order protein complexes in the regulation of
      transcription, the gene expression programmes controlled by them have remained
      largely elusive. Only recently, detailed insights into their functions have been
      obtained through the combination of a wide range of experimental methods,
      including transcriptomic and proteomic approaches. Here, we review the progress
      that has been made in the characterization of the floral organ identity factors
      from the main model plant Arabidopsis thaliana, and we discuss what is known
      about the processes acting downstream of these regulators. We further outline
      open questions, which we believe need to be addressed to obtain a more complete
      view of the molecular processes that govern floral organ development and
      specification. 

PMID- 24277280
TI  - Molecular regulation of the diatom cell cycle.
AB  - Accounting for almost one-fifth of the primary production on Earth, the
      unicellular eukaryotic group of diatoms plays a key ecological and biogeochemical
      role in our contemporary oceans. Furthermore, as producers of various lipids and
      pigments, and characterized by their finely ornamented silica cell wall, diatoms
      hold great promise for different industrial fields, including biofuel production,
      nanotechnology, and pharmaceutics. However, in spite of their major ecological
      importance and their high commercial value, little is known about the mechanisms
      that control the diatom life and cell cycle. To date, both microscopic and
      genomic analyses have revealed that diatoms exhibit specific and unique
      mechanisms of cell division compared with those found in the classical model
      organisms. Here, we review the structural peculiarities of diatom cell
      proliferation, highlight the regulation of their major cell cycle checkpoints by
      environmental factors, and discuss recent progress in molecular cell division
      research. 

PMID- 24277281
TI  - Suicidal destruction of cytochrome p-450 by ethynyl substituted compounds.
AB  - Compounds containing a terminal carbon-carbon triple bond, ranging in structure
      from the 17alpha-ethynyl substituted contraceptive steroids to acetylene gas,
      when administered to rats cause a selective and rapid time dependent loss of up
      to 50% of hepatic cytochrome P-450. Cytochrome b5 is not affected. Metabolic
      activation of the acetylenic substituent by the phenobarbital inducible, NADPH
      dependent, mixed function oxidases results in the formation of a reactive species
      which alkylates one of the tetrapyrrole nitrogen atoms of heme to form a 1 : 1
      covalent adduct. Either cytochrome P-450 destruction or the formation of N
      alkylated porphyrins (green pigments) have been used to assess factors affecting
      the extent of metabolic activation of the acetylenic group in rats, man, and
      other laboratory species. The chemical identity of a number of green pigments
      have been resolved. Those formed from 1-octyne consist of the protoporphyrin IX
      ring of heme substituted with the saturated 2-oxo-octyl group. In contrast,
      reactive metabolites of 1-octyne trapped with N-acetylcysteine contain the
      unsaturated 3-oxo-octenyl substituent. Two independent routes of activation of
      terminal acetylenes have been described to account for these results. Both
      pathways can lead to cytochrome P-450 loss but only one, probably involving an
      oxirene intermediate, leads to green pigment formation. 

PMID- 24277282
TI  - Skin structure and metabolism: relevance to the design of cutaneous therapeutics.
AB  - The outer layer of the epidermis or stratum corneum is the major barrier to
      percutaneous absorption. It has been shown that there are numerous enzyme systems
      beneath the stratum corneum in the viable epidermis capable of metabolizing
      drugs. A number of prodrug and soft drug topical therapeutic agents have been
      designed. After these agents penetrate the stratum corneum, they are metabolized
      by the cutaneous esterase systems to the desired metabolites. 

PMID- 24277283
TI  - Liquid crystals in emulsions, creams, and gels containing ethoxylated sterols as
      surfactant.
AB  - Depending on the concentration and the hydrophilicity of the surfactant,
      different mesophases have been demonstrated by X-ray analysis, polarizing
      microscopy and transmission electron microscopy of freeze-fractured samples.
      These mesophases participate in the microstructure of ternary mixtures. Mixtures
      of sterol-PEG5- and stereol-PEGlO-ether form lamellar liquid crystals which are
      organized into multilamellar vesicles with a size of up to several microns. At
      low concentrations of the surfactant the ternary systems consist of fluid
      emulsions of liquid crystalline vesicles and droplets of liquid paraffine
      dispersed in the outer hydrous phase. With increasing concentrations of the
      surfactant the mixtures become creamy and semisolid but remain emulsions with an
      increased volume ratio of the inner phase. The phase diagram of mixtures with
      sterol-PEG16-ether shows three different regions of liquid crystals: lamellar
      liquid crystals of planar arrangement at high concentration of the surfactant, a
      hexagonal mesophase with dispersed liquid paraffine and a ringing gel of close
      packed mixed micelles. The higher the volume fraction of the liquid paraffine the
      larger are the oily droplets which are dispersed in the outer liquid crystalline
      phase of the close-packed micelles. The phase diagram of the most hydrophilic
      sterol-PEG25-ether is similar to that of sterol-PEG16-ether except for the
      absence of lamellar liquid crystals. 

PMID- 24277284
TI  - Stability of liposomes on storage: freeze dried, frozen or as an aqueous
      dispersion.
AB  - For various types of liposomes carboxyfluorescein (CF) latency and physical
      stability on storage were investigated. Three regimens were compared: storage at
      4-6 degrees C in an iso-osmotic aqueous buffer, freezing of the dispersions at -5
      or -30 degrees C, or freeze drying of the dispersions. Reverse phase evaporation
      vesicles (REV) were used with mean diameters between 0.2 and 0.3 um. Liposomes
      consisted of egg phosphatidylcholine (PC) and phophatidylserine (PS) without or
      with cholesterol (chol) (9/1 and 10/1/4, respectively) or of
      distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidylglycerol (DPPG)
      without or with chol (10/l/[5]). PC/PS liposome dispersions lost 25% of the
      entrapped CF within 10 days. The leakage rate decreased with the inclusion of
      cholesterol in the bilayer. Both after a freezing/thawing cycle and after freeze
      drying no acceptable CF latency could be obtained. The cryoprotectants that were
      tested failed to raise CF latency significantly. However, the physical integrity
      of the liposomes could be maintained by proper choice of the cryoprotectant. When
      stored at 4-6 degrees C, DSPC/DPPG/(chol) dispersions were stable for at least 6
      months. Upon freezing/thawing less than 10 % CF was lost. Freeze drying without
      cryoprotectants reduced CF latency dramatically on rehydration. The physical
      structure was maintained and maximum latencies of 70 % could be obtained with the
      use of lactose as a cryoprotectant. 

PMID- 24277285
TI  - Avoidance of "first-pass" elimination of rectally administered propranolol in
      relation to the site of absorption in rats.
AB  - The extent of "first-pass" elimination of racemic propranolol and
      dextropropranolol in doses of 0.25 or 0.50 mg was investigated in relation to the
      site of drug administration in the rectum of rats. The compounds were given
      orally, i.v., and rectally at distances of 2 and 1 cm from and directly at the
      anus by low volume zero-order 30 min infusion. Unchanged propranolol was
      determined in blood, and propranolol and three metabolites were measured in
      urine. The systemic availability of propranolol after oral administration was
      approximately 6 %. Rectal administration at 2 cm, at 1 cm and directly at the
      anus (0.2 cm) gave two, three and six times higher values, respectively. The more
      distal application site produced urinary metabolite profiles that were comparable
      to those observed after oral administration, while application directly at the
      anus was similar to i.v. dosing. In all experiments log-linear elimination phases
      with comparable elimination half-lives (range 12-18 min) were found, except with
      the 0.50 mg dose after i.v. and rectal administration close to the anus which
      showed a non-linear profile. The mean systemic availability after rectal
      administration of 0.25 mg dextro-propranolol close to the anus was 50 and 64 % as
      compared to a 0.25 and 0.125 mg i.v. dose, respectively. The rectal route may be
      used for propranolol to partially prevent hepatic first-pass metabolism. However,
      avoidance of presys-temic elimination is maximal only in the immediate vicinity
      of the anus as the venous blood supply of the upper part of the rectum of rats
      appears to be connected to the portal system and the lower part to the general
      circulation. 

PMID- 24277286
TI  - Improved Delivery Through Biological Membranes. XVII. A Site-Specific Chemical
      Delivery System as a Short-Acting Mydriatic Agent.
AB  - O,O-Di(ethylsuccinyl) adrenalone was synthesized and studied as a potential short
      acting mydriatic agent. This unsymmetrical tetraester has a very short hydrolytic
      half-life in biological fluids (approximately 1 minute). The hydrolysis produces
      the inactive adrenalone. On the other hand, a reduction-hydrolytic sequence
      resulting in adrenaline was established as the mechanism of action of these types
      of compounds. The facile activation to epinephrine and fast deactivation to
      adrenalone of the unreduced chemical delivery system results in a short-acting
      mydriatic agent, a potentially important diagnostic or surgical agent. 

PMID- 24277287
TI  - Rectal motility and bioavailability.
AB  - The contractile activity of the canine rectal wall exhibits a positive influence
      on the behaviour of fatty suppositories in vivo with respect to both spreading
      abilities and rate and extent of release of the readily water-soluble compound
      phenazone. This influence on bio-availability was marked when the drug was
      suspended in a large particle size (100-125 um). When used in small particles (<
      35um), far less influence of contractile activity was found. Small particles were
      equivalent to coarse particles with respect to the bioavailability. The addition
      of colloidal silicium oxide has a marked influence on spreading and
      bioavailability. Enhanced rectal motility exhibits an influence on the absorption
      only when a coarse fraction of the drug is suspended. It was concluded that
      rectal motility might be a cause of variation in bioavailability of drugs from
      rectal suppositories. For this reason only well-trained animals should be used
      when bioavailability of drugs from suppositories is tested in an animal model. 

PMID- 24277288
TI  - Correction for Volume Shift during Equilibrium Dialysis by Measurement of Protein
      Concentration.
AB  - Volume shift during equilibrium dialysis produces errors in estimating the
      fraction of drug unbound. This study describes a method in which protein
      concentration in the plasma is used to correct binding data for volume shifts.
      Data are presented for phenytoin, a drug that does not bind to the dialysis
      system, and for verapamil, a drug that does. The conventional method of not
      correcting for volume shift, the method described previously by one of us (TNT)
      for a drug that does not bind to the dialysis system, and the proposed method of
      determining fraction unbound are compared and discussed. It is concluded that the
      second method is simple and can be used to determine the unbound fraction for a
      drug, such as phenytoin, which does not bind to the dialysis system. If a drug
      binds to the dialysis system, as does verapamil, the proposed method of measuring
      protein concentration before and after dialysis can be reliably used to correct
      for volume shift. 

PMID- 24277289
TI  - Experimental combination chemotherapy with thymidylate synthetase and
      ribonucleotide reductase inhibitors.
AB  - The synergistic cytotoxic effects on exponentially growing 9L rat brain tumor
      cells of several inhibitors of thymidylate synthetase (TS) and ribonucleotide
      reductase (RNR) used in combination were investigated using a colony forming
      efficiency assay as the experimental endpoint. A 24 h treatment with nontoxic
      (0.1 ug/ml) or low (1.0 ug/ml) doses of 5-fluorouracil (FUra), 5
      fluorodeoxyuridine, 5,8-dideazaisofolic acid, or 2'-deoxy-2'-fluoro-ara-uracil
      markedly enhanced cell kill caused by subsequent administration of 100 ug/ml
      hydroxyurea (HU) for 6 h. When a similar dose of HU or 1-formylisoquinoline
      thiosemicarbazone was administered for 6 h immediately after a 24 h treatment
      with either a 0.1 ug/ml or 1.0 ug/ml of FUra, a cell kill of approximately 1 log
      in addition to that caused by each drug alone was obtained. Thus a synergistic
      cell kill was consistently obtained when a low dose of TS inhibitors was
      administered 24 h before a 6 h treatment with another low dose of agents that act
      as RNR inhibitors. This synergism was not observed when FUra-treated cells were
      treated with methotrexate, 6-mercaptopurine, vincristine, or l,3-bis(2
      chloroethyl)-1-nitrosourea. Similarly, a 6 h treatment with 1 ug/ml of FUra of
      cells that had been treated for various periods with 100 ug/ml of HU did not
      increase cell kill more than that obtained with HU alone (30% cell kill). 

PMID- 24277290
TI  - Rapid aromatic hydrogen exchange in the antimalarial primaquine.
AB  - Primaquine, an 8-aminoquinoline antimalarial, is shown to undergo unexpectedly
      rapid aromatic proton exchange with the medium. At a pH less than 4, the exchange
      of C-5 is so fast as to be unmeasurable by proton nmr methods. At a pH of 6-6.5
      the half-time for exchange is 4 to 5 minutes. This unexpectedly high rate of
      exchange of a carbon-proton with medium may provide an important clue to the
      biological activity of primaquine. 

PMID- 24277291
TI  - Influence of volume shift in equilibrium dialysis to estimate plasma protein
      binding of drugs.

PMID- 24277292
TI  - Recent advances in ecological genomics: from phenotypic plasticity to convergent
      and adaptive evolution and speciation.
AB  - Biological diversity emerges from the interaction between genomes and their
      environment. Recent conceptual and technological developments allow dissecting
      these interactions over short and long time-scales. The 16 contributions to this
      book by leaders in the field cover major recent progresses in the field of
      Ecological Genomics. Altogether, they illustrate the interplay between the life
      history and genomic architecture of organisms, how the interaction of the
      environment and the genome is shaping phenotypic variation through phenotypic
      plasticity, how the process of adaptation may be constrained and fueled by
      internal and external features of organisms and finally, how species formation is
      the result of intricate interactions between genomes and the ecological
      conditions. These contributions also show how fundamental questions in biology
      transcend the boundaries of kingdoms, species and environments and illustrate how
      integrative approaches are powerful means to answer the most important and
      challenging questions in ecology and evolution. 

PMID- 24277293
TI  - Trait transitions in explicit ecological and genomic contexts: plant mating
      systems as case studies.
AB  - Plants are astonishingly diverse in how they reproduce sexually, and the study of
      plant mating systems provides some of the most compelling cases of parallel and
      independent evolutionary transitions. In this chapter, we review how the massive
      amount of genomic data being produced is allowing long-standing predictions from
      ecological and evolutionary theory to be put to test. After a review of
      theoretical predictions about the importance of considering the genomic
      architecture of the mating system, we focus on a set of recent discoveries on how
      the mating system is controlled in a variety of model and non-model species. In
      parallel, genomic approaches have revealed the complex interaction between the
      evolution of genes controlling mating systems and genome evolution, both genome
      wide and in the mating system control region. In several cases, major transitions
      in the mating system can be clearly associated with important ecological changes,
      hence illuminating an important interplay between ecological and genomic
      approaches. We also list a number of major unsolved questions that remain for the
      field, and highlight foreseeable conceptual developments that are likely to play
      a major role in our understanding of how plant mating systems evolve in Nature. 

PMID- 24277295
TI  - Ecological genomics of adaptation and speciation in fungi.
AB  - Fungi play a central role in both ecosystems and human societies. This is in part
      because they have adopted a large diversity of life history traits to conquer a
      wide variety of ecological niches. Here, I review recent fungal genomics studies
      that explored the molecular origins and the adaptive significance of this
      diversity. First, macro-ecological genomics studies revealed that fungal genomes
      were highly remodelled during their evolution. This remodelling, in terms of
      genome organization and size, occurred through the proliferation of non-coding
      elements, gene compaction, gene loss and the expansion of large families of
      adaptive genes. These features vary greatly among fungal clades, and are
      correlated with different life history traits such as multicellularity,
      pathogenicity, symbiosis, and sexual reproduction. Second, micro-ecological
      genomics studies, based on population genomics, experimental evolution and
      quantitative trait loci approaches, have allowed a deeper exploration of early
      evolutionary steps of the above adaptations. Fungi, and especially budding
      yeasts, were used intensively to characterize early mutations and chromosomal
      rearrangements that underlie the acquisition of new adaptive traits allowing them
      to conquer new ecological niches and potentially leading to speciation. By
      uncovering the ecological factors and genomic modifications that underline
      adaptation, these studies showed that Fungi are powerful models for ecological
      genomics (eco-genomics), and that this approach, so far mainly developed in a few
      model species, should be expanded to the whole kingdom. 

PMID- 24277294
TI  - Revisiting Mortimer's Genome Renewal Hypothesis: heterozygosity, homothallism,
      and the potential for adaptation in yeast.
AB  - In diploid organisms, the frequency and nature of sexual cycles have a major
      impact on genome-wide patterns of heterozygosity. Recent population genomic
      surveys in the budding yeast, Saccharomyces cerevisiae, have revealed surprising
      levels of genomic heterozygosity in what has been traditionally considered a
      highly inbred organism. I review evidence and hypotheses regarding the
      generation, maintenance, and evolutionary consequences of genomic heterozygosity
      in S. cerevisiae. I propose that high levels of heterozygosity in S. cerevisiae,
      arising from population admixture due to human domestication, coupled with
      selfing during rare sexual cycles, can facilitate rapid adaptation to novel
      environments. 

PMID- 24277296
TI  - Integrating phenotypic plasticity within an Ecological Genomics framework: recent
      insights from the genomics, evolution, ecology, and fitness of plasticity.
AB  - E.B. Ford's 1964 book Ecological Genetics was a call for biologists to engage in
      multidisciplinary work in order to elucidate the link between genotype,
      phenotype, and fitness for ecologically relevant traits. In this review, we argue
      that the integration of an ecological genomics framework in studies of phenotypic
      plasticity is a promising approach to elucidate the causal links between genes
      and the environment, particularly during colonization of novel environments,
      environmental change, and speciation. This review highlights some of the
      questions and hypotheses generated from a mechanistic, evolutionary, and
      ecological perspective, in order to direct the continued and future use of
      genomic tools in the study of phenotypic plasticity. 

PMID- 24277297
TI  - Eco-evo-devo: the time has come.
AB  - The major goal of ecological evolutionary developmental biology, also known as
      "eco-evo-devo," is to uncover the rules that underlie the interactions between an
      organism's environment, genes, and development and to incorporate these rules
      into evolutionary theory. In this chapter, we discuss some key and emerging
      concepts within eco-evo-devo. These concepts show that the environment is a
      source and inducer of genotypic and phenotypic variation at multiple levels of
      biological organization, while development acts as a regulator that can mask,
      release, or create new combinations of variation. Natural selection can
      subsequently fix this variation, giving rise to novel phenotypes. Combining the
      approaches of eco-evo-devo and ecological genomics will mutually enrich these
      fields in a way that will not only enhance our understanding of evolution, but
      also of the genetic mechanisms underlying the responses of organisms to their
      natural environments.

PMID- 24277298
TI  - Evolutionary and ecological genomics of developmental plasticity: novel
      approaches and first insights from the study of horned beetles.
AB  - Phenotypic plasticity pervades organismal development and physiology where it
      facilitates an enormous range of adaptive responses to novel or stressful
      environments. Plasticity also impacts evolutionary processes, reducing the
      probability of population extinction in the face of environmental changes and
      sometimes increasing speciation rates in developmentally plastic lineages.
      Despite the adaptive significance of plasticity, organisms are not infinitely
      plastic; rather they are constrained in the kinds and ranges of environmental
      changes to which their body parts, organs, and tissues can respond. Understanding
      the nature, costs, and limits of developmental plasticity requires insight into
      (i) the developmental-genetic and genomic mechanisms underlying plastic responses
      as well as (ii) their interplay with ecological and social conditions. In this
      chapter we review and summarize recent progress in the development of horned
      beetles as a study system with which to explore the interactions between changing
      ecological conditions and plastic, genome-wide responses in gene expression and
      developmental function. In particular, we focus on plastic responses to
      nutritional variation, which in horned beetles differ widely as a function of
      body region, sex, and species. We begin by introducing the study system and
      summarize the developmental-genetic and genomic tool set currently available for
      horned beetles. We then present recently developed statistical approaches that
      can be used to guide the design of multi-factorial genome-wide transcriptional
      comparisons when circumstances prohibit a fully balanced design. We present an
      example of such an approach in the horned beetle Onthophagus taurus and end by
      highlighting the growing opportunities for future ecological-genomic studies in
      horned beetles. 

PMID- 24277299
TI  - Neurogenomics of behavioral plasticity.
AB  - Across animals, there is remarkable diversity in behavior. Modern genomic
      approaches have made it possible to identify the molecular underpinnings of
      varied behavioral phenotypes. By examining species with plastic phenotypes we
      have begun to understand the dynamic and flexible nature of neural transcriptomes
      and identified gene modules associated with variation in social and reproductive
      behaviors in diverse species. Importantly, it is becoming increasingly clear that
      some candidate genes and gene networks are involved in complex social behaviors
      across even divergent species, yet few comparative transcriptomics studies have
      been conducted that examine a specific behavior across species. We discuss the
      implications of a range of important and insightful studies that have increased
      our understanding of the neurogenomics of behavioral plasticity. Despite its
      successes, behavioral genomics has been criticized for its lack of hypotheses and
      causative insights. We propose here a novel avenue to overcome some of these
      short-comings by complementing "forward genomics" studies (i.e., from phenotype
      to behaviorally relevant gene modules) with a "reverse genomics" approach (i.e.,
      manipulating novel gene modules to examine effects on behavior, hormones, and the
      genome itself) to examine the functional causes and consequences of differential
      gene expression patterns. We discuss how several established approaches (such as
      pharmacological manipulations of a novel candidate pathway, fine scale mapping of
      novel candidate gene expression in the brain, or identifying direct targets of a
      novel transcription factor of interest) can be used in combination with the
      analysis of the accompanying neurogenomic responses to reveal unexpected
      biological processes. The integration of forward and reverse genomics will move
      the field beyond statistical associations and yield great insights into the
      neural and molecular control of social behavior and its evolution. 

PMID- 24277300
TI  - Ecological genomics of host behavior manipulation by parasites.
AB  - Among the vast array of niche exploitation strategies exhibited by millions of
      different species on Earth, parasitic lifestyles are characterized by extremely
      successful evolutionary outcomes. Some parasites even seem to have the ability to
      'control' their host's behavior to fulfill their own vital needs. Research
      efforts in the past decades have focused on surveying the phylogenetic diversity
      and ecological nature of these host-parasite interactions, and trying to
      understand their evolutionary significance. However, to understand the proximal
      and ultimate causes of these behavioral alterations triggered by parasitic
      infections, the underlying molecular mechanisms governing them must be uncovered.
      Studies using ecological genomics approaches have identified key candidate
      molecules involved in host-parasite molecular cross-talk, but also molecules not
      expected to alter behavior. These studies have shown the importance of following
      up with functional analyses, using a comparative approach and including a time
      series analysis. High-throughput methods surveying different levels of biological
      information, such as the transcriptome and the epigenome, suggest that specific
      biologically-relevant processes are affected by infection, that sex-specific
      effects at the level of behavior are recapitulated at the level of transcription,
      and that epigenetic control represents a key factor in managing life cycle stages
      of the parasite through temporal regulation of gene expression. Post
      translational processes, such as protein-protein interactions (interactome) and
      post translational modifications (e.g. protein phosphorylation, phosphorylome),
      and processes modifying gene expression and translation, such as interactions
      with microRNAs (microRNAome), are examples of promising avenues to explore to
      obtain crucial insights into the proximal and ultimate causes of these
      fascinating and complex inter-specific interactions.

PMID- 24277301
TI  - Ecological epigenetics.
AB  - Biologists have assumed that heritable variation due to DNA sequence differences
      (i.e., genetic variation) allows populations of organisms to be both robust and
      adaptable to extreme environmental conditions. Natural selection acts on the
      variation among different genotypes and ultimately changes the genetic
      composition of the population. While there is compelling evidence about the
      importance of genetic polymorphisms, evidence is accumulating that epigenetic
      mechanisms (e.g., chromatin modifications, DNA methylation) can affect
      ecologically important traits, even in the absence of genetic variation. In this
      chapter, we review this evidence and discuss the consequences of epigenetic
      variation in natural populations. We begin by defining the term epigenetics,
      providing a brief overview of various epigenetic mechanisms, and noting the
      potential importance of epigenetics in the study of ecology. We continue with a
      review of the ecological epigenetics literature to demonstrate what is currently
      known about the amount and distribution of epigenetic variation in natural
      populations. Then, we consider the various ecological contexts in which
      epigenetics has proven particularly insightful and discuss the potential
      evolutionary consequences of epigenetic variation. Finally, we conclude with
      suggestions for future directions of ecological epigenetics research. 

PMID- 24277302
TI  - The reproducibility of adaptation in the light of experimental evolution with
      whole genome sequencing.
AB  - A key question in evolutionary biology is the reproducibility of adaptation. This
      question can now be quantitatively analyzed using experimental evolution coupled
      to whole genome sequencing (WGS). With complete sequence data, one can assess
      convergence among replicate populations. In turn, convergence reflects the action
      of natural selection and also the breadth of the field of possible adaptive
      solutions. That is, it provides insight into how many genetic solutions or
      adaptive paths may lead to adaptation in a given environment. Convergence is both
      a property of an adaptive landscape and, reciprocally, a tool to study that
      landscape. In this chapter we present the links between convergence and the
      properties of adaptive landscapes with respect to two types of microbial
      experimental evolution. The first tries to reconstruct a full adaptive landscape
      using a handful of carefully identified mutations (the reductionist approach),
      while the second uses WGS of replicate experiments to infer properties of the
      adaptive landscape. Reductionist approaches have highlighted the importance of
      epistasis in shaping the adaptive landscape, but have also uncovered a wide
      diversity of landscape architectures. The WGS approach has uncovered a very high
      diversity of beneficial mutations that affect a limited set of genes or functions
      and also suggests some shortcomings of the reductionist approach. We conclude
      that convergence may be better defined at an integrated level, such as the genic
      level or even at a phenotypic level, and that integrated mechanistic models
      derived from systems biology may offer an interesting perspective for the
      analysis of convergence at all levels. 

PMID- 24277303
TI  - Ecological genomics of host shifts in Drosophila mojavensis.
AB  - Advances in next-generation sequencing technologies have liberated our dependency
      on model laboratory species for answering genomic and transcriptomic level
      questions. These new techniques have dramatically expanded our breadth of study
      organisms and have allowed the analysis of species from diverse ecological
      environments. One such species is the cactophilic Drosophila mojavensis that
      inhabits the deserts of western North America. These insects feed and develop in
      the necrotic cacti, feeding largely on the microflora of the necrotic plant
      tissues. Drosophila mojavensis is composed of four geographically and
      ecologically separated populations. Each population (Baja California peninsula,
      mainland Sonoran Desert, Mojave Desert and Santa Catalina Island) utilizes the
      necrotic tissues of distinct cactus species. The differences in the nutritional
      and chemical composition of the necroses include a set of toxic compounds to
      which resident population must adapt. These ecological differences have
      facilitated many of the life history, behavior, physiological and genetic
      differences between the cactus host populations. Genomic resources have allowed
      investigators to examine the genomic and transcriptional level changes associated
      with the local adaptation of the four D. mojavensis populations, thereby
      providing further understanding of the genetic mechanism of adaptation and its
      role in the divergence of ecologically distinct populations. 

PMID- 24277304
TI  - The genomics of an adaptive radiation: insights across the Heliconius speciation
      continuum.
AB  - Fueled by new technologies that allow rapid and inexpensive assessment of fine
      scale individual genomic variation, researchers are making transformational
      discoveries at the interface between genomes and biological complexity. Here we
      review genomic research in Heliconius butterflies - a radiation characterized by
      extraordinary phenotypic diversity in warningly colored wing patterns and
      composed of a continuum of taxa across the stages of speciation. These
      characteristics, coupled with a 50-year legacy of ecological and behavioral
      research, offer exceptional prospects for genomic studies into the nature of
      adaptive differences and the formation of new species. Research in Heliconius
      provides clear connections between genotype, phenotype, and fitness of wing color
      patterns shown to underlie adaptation and speciation. This research is
      challenging our perceptions about how speciation occurs in the presence of gene
      flow and the role of hybridization in generating adaptive novelty. With the
      release of the first Heliconius genome assembly, emerging genomic studies are
      painting a dynamic picture of the evolving species boundary. As the field of
      speciation genomics moves beyond describing patterns, towards a more integrated
      understanding of the process of speciation, groups such as Heliconius, where
      there is a clear speciation continuum and the traits underlying adaptation and
      speciation are known, will provide a roadmap for identifying variation crucial in
      the origins of biodiversity. 

PMID- 24277305
TI  - Merging ecology and genomics to dissect diversity in wild tomatoes and their
      relatives.
AB  - To understand the origin, history, and function, of natural biological variation,
      from nucleotide to community levels, is a fundamental promise of ecological
      genomics. The most fruitful systems for this work are those that possess both
      ecological and genomic resources. Such systems provide an opportunity to
      precisely dissect genetic and developmental mechanisms, and to connect genotypes
      to phenotypes, as well as to directly demonstrate the ecological and evolutionary
      relevance of this phenotypic variation. Here we synthesize findings emerging from
      our efforts to understand two fundamental evolutionary processes - speciation and
      adaptation - using ecological genomics approaches. Many of these studies have
      been in the wild tomato clade (Solanum section Lycopersicon), a group that has
      both exceptional diversity and genomic tools. We also highlight the expanding
      taxonomic reach of this work, especially in two genera - Capsicum and Jaltomata -
      that are closely related to Solanum. Parallel approaches in these ecologically
      and reproductively diverse clades enable us to examine novel questions and traits
      that are not captured within Solanum, while leveraging the power of comparative
      studies to understand shared ecological and evolutionary patterns. By
      synthesizing findings from phenotypic, ecophysiological, genetic, and comparative
      perspectives, our ultimate goal is to understand the complex mechanistic and
      evolutionary contributions to the formation of new traits and species diversity. 

PMID- 24277306
TI  - Integrated genomics approaches in evolutionary and ecological endocrinology.
AB  - Hormones can act on a variety of target tissues to regulate the expression of
      multiple phenotypic traits. Therefore, phenotypes regulated by the same hormones
      can be genetically correlated due to their common regulatory mechanism. Such
      genetic correlations may either facilitate or constrain adaptive evolution. In
      addition, hormone signaling pathways are regulated by external environmental
      factors, so hormones can mediate phenotypic plasticity and polyphenism. When
      different responses to environmental signals are favored, hormone signaling
      pathways can vary between populations and species exploiting dissimilar
      environments and thus mediate genotype-by-environment interactions. A complete
      understanding of the evolutionary causes and ecological implications of hormone
      signal variation requires examining several components of hormone signaling
      pathways across multiple individuals, populations, and species. Genomic
      technologies are excellent tools for undertaking genetic studies of naturally
      occurring variation in hormone signals. In this chapter, we review how genomic
      approaches can help to answer major questions in evolutionary endocrinology,
      including how environmental cues can be translated into phenotypic development
      through hormone pathways, how multiple hormone-mediated phenotypic traits are
      coupled and decoupled, how gene functions in hormone pathways influence the
      evolutionary rate of genes, and how divergence in hormone pathways can contribute
      to phenotypic diversification and speciation in non-model organisms. We also
      discuss how emerging analytical and experimental technologies in genomics and
      hormone measurement can provide valuable new insights into the roles of hormone
      signal variation in adaptive evolution and phenotypic diversification. 

PMID- 24277307
TI  - Evolutionary genomics of environmental pollution.
AB  - Chemical toxins have been a persistent source of evolutionary challenges
      throughout the history of life, and deep within the genomic storehouse of
      evolutionary history lay ancient adaptations to diverse chemical poisons.
      However, the rate of change of contemporary environments mediated by human
      introduced pollutants is rapidly screening this storehouse and severely testing
      the adaptive potential of many species. In this chapter, we briefly review the
      deep history of evolutionary adaptation to environmental toxins, and then proceed
      to describe the attributes of stressors and populations that may facilitate
      contemporary adaptation to pollutants introduced by humans. We highlight that
      phenotypes derived to enable persistence in polluted habitats may be multi
      dimensional, requiring global genome-scale tools and approaches to uncover their
      mechanistic basis, and include examples of recent progress in the field. The
      modern tools of genomics offer promise for discovering how pollutants interact
      with genomes on physiological timescales, and also for discovering what genomic
      attributes of populations may enable resistance to pollutants over evolutionary
      timescales. Through integration of these sophisticated genomics tools and
      approaches with an understanding of the deep historical forces that shaped
      current populations, a more mature understanding of the mechanistic basis of
      contemporary ecological-evolutionary dynamics should emerge. 

PMID- 24277308
TI  - Signatures of natural selection and ecological differentiation in microbial
      genomes.
AB  - We live in a microbial world. Most of the genetic and metabolic diversity that
      exists on earth - and has existed for billions of years - is microbial. Making
      sense of this vast diversity is a daunting task, but one that can be approached
      systematically by analyzing microbial genome sequences. This chapter explores how
      the evolutionary forces of recombination and selection act to shape microbial
      genome sequences, leaving signatures that can be detected using comparative
      genomics and population-genetic tests for selection. I describe the major classes
      of tests, paying special attention to their relative strengths and weaknesses
      when applied to microbes. Specifically, I apply a suite of tests for selection to
      a set of closely-related bacterial genomes with different microhabitat
      preferences within the marine water column, shedding light on the genomic
      mechanisms of ecological differentiation in the wild. I will focus on the joint
      problem of simultaneously inferring the boundaries between microbial populations,
      and the selective forces operating within and between populations. 

PMID- 24277310
TI  - Stress management delivered over public television: Steps toward promoting
      community mental health.
AB  - This study evaluated the efficacy of television as a teaching and skills
      developing medium in the area of health promotion. Experimental subjects viewed a
      five-part stress management series aired on public television. Control subjects
      were not told about the series. All subjects completed a stress questionnaire
      battery before and after the televised series and again at a six-week follow-up.
      The results indicated that experimental subjects learned about stress and stress
      management from the program. Those experimental subjects who watched four or five
      segments of the series tended to score higher on stress knowledge than did
      subjects who viewed fewer than three segments. No significant differences were
      found between experimental and control subjects on other self-report measures.
      Theoretical and methodological issues are discussed. 

PMID- 24277309
TI  - Increased number of Langerhans cells in the epidermis of diabetic foot ulcers
      correlates with healing outcome.
AB  - Langerhans cells (LCs) are a specialized subset of epidermal dendritic cells.
      They represent one of the first cells of immunologic barrier and play an
      important role during the inflammatory phase of acute wound healing. Despite
      considerable progress in our understanding of the immunopathology of diabetes
      mellitus and its associated comorbidities such as diabetic foot ulcers (DFUs),
      considerable gaps in our knowledge exist. In this study, we utilized the human ex
      vivo wound model and confirmed the increased epidermal LCs at wound edges during
      early phases of wound healing. Next, we aimed to determine differences in
      quantity of LCs between normal human and diabetic foot skin and to learn if the
      presence of LCs correlates with the healing outcome in DFUs. We utilized
      immunofluorescence to detect CD207+ LCs in specimens from normal and diabetic
      foot skin and DFU wound edges. Specimens from DFUs were collected at the initial
      visit and 4 weeks later at the time when the healing outcome was determined. DFUs
      that decreased in size by >50 % were considered to be healing, while DFUs with a
      size reduction of <50 % were considered non-healing. Quantitative assessment of
      LCs showed a higher number of LCs in healing when compared to non-healing DFU's.
      Our findings provide evidence that LCs are present in higher number in diabetic
      feet than normal foot skin. Healing DFUs show a higher number of LCs compared to
      non-healing DFUs. These findings indicate that the epidermal immune barrier plays
      an important role in the DFU healing outcome and may offer new therapeutic
      avenues targeting LC in non-healing DFUs.

PMID- 24277311
TI  - Evaluation of an affective development teacher training program.
AB  - Effective Classroom Management (ECM), an affective development course, was
      provided to fifth grade teachers. Teachers were taught techniques in
      communication, classroom management, and self-esteem enhancement to make
      classroom environments more responsive to students' affective and cognitive
      needs. Schools were matched and one school from each pair was randomly assigned
      to either the experimental or control condition. There were 11 experimental and
      11 control classes. Teachers in seven of the experimental classes completed the
      training. No predicted treatment effects on teachers or students were found.
      Discussion is in terms of generic approaches of primary prevention. 

PMID- 24277312
TI  - A reflective approach to preventing alcohol abuse in youth.
AB  - A reflective approach to alcohol abuse prevention uses a group survey format to
      measure knowledge, attitude, and alcohol use, and presents the results to
      students for discussion. The program respects the students' rights of anonymity,
      and yet provides information to them about peer knowledge, attitude, and use of
      alcohol so that group norms can be identified. Each student can then compare his
      or her actions and attitudes to those of others. The program has been well
      received by junior high school youth, requires minimal teacher preparation, and
      appears promising for preventing abusive alcohol use. This article describes the
      technique's background, measurement and discussion methods, and implications for
      a range of prevention activities. 

PMID- 24277314
TI  - Prevention/promotion with minorities.

PMID- 24277313
TI  - Parent groups in drug abuse prevention: Is this the constituency we've been
      waiting for?
AB  - Prevention, although always intended to be a focus of community mental health
      centers, has suffered from lack of a defined constituency. In lean economic years
      when federal policy dictates private sector support, these resources become
      critical. For prevention of drug abuse, concerned parents across the country have
      joined together to form support groups. Are these parents groups the resource
      that mental health professionals need? Does this new breed of parent groups want
      to be one of our constituencies? Are mental health professionals willing to make
      the necessary adjustments in attitudes, management styles, and programs to reap
      the benefits of these new groups? This article explores experiences of working
      with a few parent groups in two different areas of the country in an effort to
      encourage prevention professionals to strengthen collaborative ties. 

PMID- 24277315
TI  - Fundamentals of robotic surgery: a course of basic robotic surgery skills based
      upon a 14-society consensus template of outcomes measures and curriculum
      development.
AB  - BACKGROUND: There is a need for a standardized curriculum for training and
      assessment of robotic surgeons to proficiency, followed by high-stakes testing
      (HST) for certification. METHODS: To standardize the curriculum and certification
      of robotic surgeons, a series of consensus conferences attended by 14 leading
      international surgical societies have been used to compile the outcomes measures
      and curriculum that should form the basis for a Fundamentals of Robotic Surgery
      (FRS) programme. RESULTS: A set of 25 outcomes measures and a curriculum for
      teaching the skills needed to safely use current generation surgical robotic
      systems has been developed and accepted by a committee of experienced robotic
      surgeons across 14 specialties. CONCLUSIONS: A standardized process for
      certifying the skills of a robotic surgeon has begun to emerge. The work
      described here documents both the processes used for developing educational
      material and the educational content of a robotic curriculum.

PMID- 24277316
TI  - Delinquency and learning disabilities: Evidence for compensatory behaviors and
      adaptation.
AB  - There has been a great deal of debate as to whether or not there is a direct
      relationship between learning disabilities and delinquent behavior. While the
      relationship was well established for adjudicated youth, it was more uncertain
      for adolescents not actively involved with the juvenile justice system. There are
      indications, however, that the relationship is more complex, with learning
      disabled (LD) adolescents more likely to develop severe delinquent behaviors than
      are their nondisabled peers, but unlikely to exhibit a middle ground between
      delinquent and nondelinquent behavior. It is hypothesized that this difference is
      due to the ability of most LD children and adolescents to adapt through
      developing skills that allow them to compensate for their handicapping
      conditions. Implications for future research are discussed. 

PMID- 24277317
TI  - Alcohol abuse prevention among Latino adolescents: A strategy for intervention.
AB  - In spite of what is known about adolescent alcohol use and the need to prevent
      alcohol abuse, there is a scarcity of information on alcohol use and alcohol
      abuse among Latino youth. This paper describes the results of a unique prevention
      program funded by the National Institute of Alcohol Abuse and Alcoholism in 1978
      for Latino youth (12-17 years of age) in East Harlem. Existing literature on
      Latino youth and alcohol use is reviewed, followed by a description of the
      program, its setting, and its evaluative methodology. The methodological strategy
      entailed in-depth interviews with 80 program participants and interviews with
      staff. The results clearly demonstrate changes in alcohol knowledge, attitudes,
      and behavior among consistent participants, who constituted about one-third of
      the 752 participants. The changes were most attributable to the intervention
      strategies used, namely workshops and cultural materials, as well as outreach to
      parents and role modeling by staff. The most enlightening results were in terms
      of reasons for participation and attrition. The final section describes the need
      for the development of creative educational methods and materials, and
      difficulties in the use of traditional educational curriculum and evaluation
      materials with low-income Latino youth. 

PMID- 24277318
TI  - A behavior profile of polydrug abusers.
AB  - Polydrug abusers have been thought to present with characteristic behavior
      profiles and to suffer from brain damage. In this study, an attempt was made to
      delineate the behavior characteristics of polydrug abusers using the Personality
      Inventory developed by Bear and Fedio for temporal lobe epilepsy (TLE). In
      addition to a group of normal youths, a contrast group comparable to the polydrug
      abusers in psychiatric history, education, socioeconomic status, and family
      history was employed. Results revealed that for almost all traits the scores of
      polydrug abusers were the most extreme, while those of the controls the least,
      with the scores of the contrast group falling in between. The inventory correctly
      classified 87% of the experimental, 81% of the control, and 71% of the contrast
      group. The profile of personality traits that identified the polydrug abusers
      considerably overlapped with the profile of TLEs reported by Bear and Fedio,
      although the significance of the overlap is at present unclear. Future research
      is suggested to examine a possible limbic system involvement in polydrug abuse. 

PMID- 24277319
TI  - Orientations to the future: A comparison of adolescents in Australia and
      Singapore.
AB  - Using an event-listing approach, this study examined the personal and societal
      future orientations of 15-year-old males and females in Singapore and Sydney.
      Three aspects were examined: content, affect, and time span. Overall, the study
      found that adolescents perceived their personal and societal features in separate
      noninterlocking planes, seeing more pleasant, proximal, personal futures, and
      more unpleasant, distal, societal futures, especially in relation to nuclear war
      and political problems. Demographic and personal construct variables influenced
      this general pattern of future orientation. 

PMID- 24277320
TI  - Maternal regulation and adolescent autonomy: Mother-daughter resolution of story
      conflicts.
AB  - To examine how maternal regulation and daughters' striving for autonomy are
      reflected in dyadic communication, 32 eighth- and twelfth-grade daughters and
      their mothers were audiotaped as they discussed two stories with unresolved
      mother-daughter conflict themes (daughter's pregnancy, mother's financial
      problem). The tapes were analyzed for the quality of the conversational
      statements made while resolving the story conflicts. Results indicated that
      mothers regulated conversation through questions while daughters were more
      conceding. This pattern was less marked in older dyads. Five dyadic interaction
      styles were identified and examined in relation to grade level of the daughters.
      The results are discussed in light of issues of regulation and autonomy during
      adolescence and adulthood. 

PMID- 24277321
TI  - Self-reported delinquency and home life: Evidence from a sample of British girls.
AB  - This study examines the correlation between family variables and delinquency
      (both self-reported and official) in a small sample of British teenage girls.
      Factor analysis of the 72-item Home Life Questionnaire (from T. H. Hirschi [1969]
      Causes of Delinquency, University of California Press, Berkeley) revealed a clear
      four-factor structure of caring and communication, discipline, pressure and
      mother-daughter closeness, which cumulatively accounted for 31% of the variance.
      Multiple regression of these factors onto self-reported delinquency indicated the
      maternal factor to be most powerful, explaining 25% of the variance in self
      reported delinquency. Institutionalized and noninstitutionalized girls showed
      only chance differences in terms of the quality of their home life. 

PMID- 24277322
TI  - An application of Gough's conceptual model to a measure of adolescent self
      esteem.
AB  - The concept of self-esteem is central in psychology, but few well-validated
      measures exist. This paper presents some preliminary data on the Self-Esteem
      Questionnaire (SEQ) organized along Gough's conceptual model of primary,
      secondary, and tertiary evaluation. The SEQ appears to discriminate groups along
      a self-esteem continuum; fits in well with a variety of theoretical approaches;
      does not have nuisance loadings on sex, intelligence, or social status; is unduly
      affected by social desirability; and correlates well with standard measures of
      self-esteem. 

PMID- 24277323
TI  - Ecophysiological properties of cultivable heterotrophic bacteria and yeasts
      dominating in phytocenoses of Galindez Island, maritime Antarctica.
AB  - Antarctic plants are stable specific microenvironments for microbial colonization
      that are still less explored. In this study, we investigated cultivable
      heterotrophic bacteria and yeasts dominating in plant samples collected from
      different terrestrial biotopes near Ukrainian Antarctic Base on Galindez Island,
      maritime Antarctica. Phylogenetic analysis revealed affiliation of the bacterial
      isolates to genera Pseudomonas, Stenotrophomonas, Brevundimonas, Sporosarcina,
      Dermacoccus, Microbacterium, Rothia and Frondihabitans, and the yeast isolates to
      genera Rhodosporidium, Cryptococcus, Leucosporidiella, Candida and Exophiala.
      Some ecophysiological properties of isolated strains were determined that are
      important in response to different stresses such as psychro- and halotolerance,
      UV-resistance and production of hydrolytic enzymes. The majority of isolates (88
      %) was found to be psychrotolerant; all are halotolerant. Significant differences
      in survival subsequent to UV-C radiation were observed among the isolates, as
      measured by culturable counts. For the bacterial isolates, lethal doses in the
      range 80-600 J m-2 were determined, and for the yeast isolates--in the range 300
      1,000 J m-2. Dermacoccus profundi U9 and Candida davisiana U6 were found as most
      UV resistant among the bacterial and yeast isolates, respectively. Producers of
      caseinase, gelatinase, beta-glucosidase, and cellulase were detected. To the best
      of our knowledge, this is the first report on isolation of UV resistant strain D.
      profundi, and Frondihabitans strain from Antarctica, and on detection of
      cellulase activity in Antarctic yeast strain C. davisiana. The results obtained
      contribute to clarifying adaptation strategies of Antarctic microbiota and its
      possible role in functional stability of Antarctic biocenoses. Stress tolerant
      strains were detected that are valuable for ecological and applied studies.

PMID- 24277325
TI  - Characteristics influencing therapy switch behavior after suboptimal response to
      first-line treatment in patients with multiple sclerosis.
AB  - BACKGROUND: Factors driving disease-modifying therapy (DMT) switch behavior are
      not well understood. OBJECTIVE: The objective of this paper is to identify
      patient characteristics and clinical events predictive of therapy switching in
      patients with suboptimal response to DMT. METHODS: This retrospective study
      analyzed patients with relapsing-remitting multiple sclerosis (MS) and a
      suboptimal response to initial therapy with either interferon beta or glatiramer
      acetate. Suboptimal responders were defined as patients with >=1 MS event
      (clinical relapse, worsening disability, or MRI worsening) while on DMT.
      Switchers were defined as those who changed DMT within six to 12 months after the
      MS event. RESULTS: Of 606 suboptimal responders, 214 (35.3%) switched therapy.
      Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004),
      DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with
      nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly
      predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed
      by >=2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5;
      95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p =
      0.009). CONCLUSIONS: Younger patients with disease activity, especially MRI
      changes, are more likely to have their therapy switched sooner than patients who
      are older at the time of MS diagnosis and DMT initiation.

PMID- 24277324
TI  - Genetic burden of common variants in progressive and bout-onset multiple
      sclerosis.
AB  - BACKGROUND: The contribution of genetic variants underlying the susceptibility to
      different clinical courses of multiple sclerosis (MS) is still unclear.
      OBJECTIVE: The aim of the study is to evaluate and compare the proportion of
      liability explained by common SNPs and the genetic burden of MS-associated SNPs
      in progressive onset (PrMS) and bout-onset (BOMS) cases. METHODS: We estimated
      the proportion of variance in disease liability explained by 296,391 autosomal
      SNPs in cohorts of Italian PrMS and BOMS patients using the genome-wide complex
      trait analysis (GCTA) tool, and we calculated a weighted genetic risk score
      (wGRS) based on the known MS-associated loci. RESULTS: Our results identified
      that common SNPs explain a greater proportion of phenotypic variance in BOMS
      (36.5%+/-10.1%) than PrMS (20.8%+/-6.0%) cases, and a trend of decrease was
      observed when testing primary progressive (PPMS) without brain MRI inflammatory
      activity (p = 7.9 * 10(-3)). Similarly, the wGRS and the variance explained by MS
      associated SNPs were higher in BOMS than PPMS in males (wGRS: 6.63 vs 6.51, p =
      0.04; explained variance: 4.8%+/-1.5% vs 1.7%+/-0.6%; p = 0.05). CONCLUSIONS: Our
      results suggest that the liability of disease is better captured by common
      genetic variants in BOMS than PrMS cases. The absence of inflammatory activity
      and male gender further raise the difference between clinical courses.

PMID- 24277326
TI  - Indicators for cognitive performance and subjective cognitive complaints in
      multiple sclerosis: a role for advanced MRI?
AB  - Previous studies showed that advanced neuroimaging measures (functional MRI,
      diffusion tensor imaging) could distinguish multiple sclerosis (MS) patients with
      and without cognitive impairment. Are these measures indeed better indicators for
      cognitive impairment or subjective cognitive complaints than conventional MRI?
      Fifty MS patients and 29 controls were investigated. Regression analysis,
      including socio-demographic data, disease characteristics, psychological
      measures, and (advanced) neuroimaging, showed that worse cognitive performance
      was associated with male sex, lower education, and lower gray matter volume.
      Subjective cognitive complaints were associated with fatigue and less hippocampal
      atrophy. Advanced MRI measures did not add to the predictive power of our model.

PMID- 24277327
TI  - Extraction of natural substances with dense gases.
AB  - An overview of the solvent power of dense gases is given. The properties of these
      novel solvents are described and the specific advantages of carbon dioxide
      discussed. New qualitative and quantitative procedures for the rapid
      determination of solubilities are described for several interesting classes of
      natural substances. These include fatty oils, steroids, alkaloids, flavor and
      aroma substances, which documents the versatility of the new extraction procedure
      in many practical applications. 

PMID- 24277328
TI  - Pyrazolopyrimidine metabolism in parasitic protozoa.
AB  - The pyrazolopyrimidines are purine analogs that are cytotoxic toward and
      metabolized by several genera of parasitic protozoa, including the Leishmania and
      the Trypanosoma. Examples of pyrazolopyrimidines that are selectively metabolized
      by these parasites include allopurinol, allopurinol riboside, 4-thiopurinol, 4
      thiopurinol riboside, and formycin B. These pathogenic protozoa are capable of
      efficient conversion of the pyrazolopyrimidines to the nucleotide level. The
      pyrazolopyrimidine metabolites which are isomers of inosine monophosphate are
      subsequently aminated and incorporated as the adenylate analog into RNA.
      Mammalian cells are incapable of these metabolic transformations. The sulfur
      containing pyrazolopyrimidines, however, are neither aminated nor incorporated
      into nucleic acid. The selective metabolism of the pyrazolopyrimidines by the
      intracellular metabolic machinery of the parasites of the Trypanosomatidae family
      offers a rational approach to the chemotherapy of the diseases caused by these
      pathogenic hemoflagellates. 

PMID- 24277329
TI  - Pharmacokinetics and metabolic fate of two nitroxides potentially useful as
      contrast agents for magnetic resonance imaging.
AB  - Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in
      magnetic resonance imaging (MRI) experiments in animals. Preliminary information
      on the metabolic fate, pharmacokinetic behavior, stability in tissues, and
      chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In
      the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of
      both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in
      vivo to their corresponding hydroxylamines. No other metabolite was observed.
      Measured reducing activity in tissue homogenates was greater in liver or kidney
      than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA
      was also more resistant to reduction by ascorbic acid at physiologic pH. These
      preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a
      piperidinyl nitroxide, for MRI contrast enhancement. 

PMID- 24277330
TI  - Radioreceptor assay of narcotic analgesics in serum.
AB  - A sensitive radioreceptor assay (RRA) to determine the serum concentrations of
      fentanyl, pentazocine and morphine was developed on the basis of the drug's
      competition with a labeled tracer ((3)H-naloxone) for the membrane bound opioid
      receptor in rat brain homogenates. The binding data were computer-fitted to a
      standard curve by means of nonlinear least square regression. Sensitivity of the
      assay applied directly to serum samples without extraction was limited to
      approximately 3, 5 and 25 ng/ml for fentanyl, morphine and pentazocine,
      respectively, because of endogenous plasma constituents that interfere with the
      opioid receptor binding. With the use of petrol-ether extraction the sensitivity
      was improved to 0.3 ng/ml fentanyl and 3 ng/ml pentazocine (0.3 ml serum
      samples). No RRA-active metabolites were detectable after HPLC separation of
      serum from a patient treated with fentanyl. The plasma concentration time course
      of fentanyl in a patient, measured by RRA, was similar to that obtained by a
      radioimmunoassay (RIA). The RRA represents a general procedure for the detection
      of clinically used opioid analgesics and their active metabolites. 

PMID- 24277331
TI  - A radioimmunoassay for determination of glibenclamide and other sulfonylureas.
AB  - An antiserum was prepared for the determination of glibenclamide and for the
      estimation of other commercially available sulfonylureas. Rabbits were immunized
      with a glibenclamide-BSA conjugate. Tritiated glibenclamide was used as the
      tracer. The assay was performed in the presence of 8-anilinonaphthalenesulfonic
      acid to displace glibenclamide bound to serum protein, and free and antibody
      bound tracer were separated by dextran-coated charcoal. For glibenclamide
      determination in serum and plasma the limit of detection was 3 ng/ml. Sensitivity
      calculated for the whole determination range was 102 cpm for a 10 % concentration
      difference. Specificity studies showed a cross-reaction of less than 0.1 % for
      glibenclamide metabolite M1 and 9 % for metabolite M2. Other sulfonylurea drugs
      display cross-reactivities from 0.1% (chlorpropamide) to 190% (gliquidone). Both
      intra-assay and inter-assay imprecision were below 10 %. Accuracy was established
      by comparison of the present method with HPLC. The assay was applied to the
      specific determination of glibenclamide in clinical trials and for diagnosing
      factitious hypoglycemia caused by sulfonylureas. 

PMID- 24277332
TI  - Transmucosal passage of liposomally-entrapped drugs in rat small intestine.
AB  - Intestinal absorption of liposomally-entrapped drugs was investigated for egg
      yolk phosphatidylcholine-cholesterol (2:1 by molar ratio) liposomes (EggPC
      liposome) and distearoylphosphatidylcholine-cholesterol (2:1) liposomes (DSPC
      liposome). The release of carboxyfluorescein, an aqueous phase marker, induced by
      the presence of everted rat intestine was 40 % and 6 % in one hour from DSPC
      liposomes and EggPC liposomes, respectively, and it is suggested that EggPC
      liposomes are more stable in the intestinal lumen. The transport of a liposomally
      entrapped drug was examined with fluoresceinisothiocyanate-conjugated dextran
      (FITC-D) as a model drug that has a small mucosal-to-serosal clearance because of
      its high average molecular weight (64200). The clearance of FITC-D entrapped in
      DSPC liposomes was largely reduced and could be accounted for by the clearance of
      the extraliposomal FITC-D concentration in the preparation. On the other hand,
      the calculated clearance of EggPC liposome-associated FITC-D was similar to or
      even higher than that of free FITC-D. The serosal appearance of the EggPC
      liposome-associated drug was inhibited by colchicine, cytochalasin B, and
      iodoacetate, suggesting that the liposome was incorporated into the epithelial
      cells by endocytosis. However, the observation that a lipid phase marker, (14)C
      dipalmitoylphosphatidylcholine, failed to be transported into the serosal fluid
      indicates the absence of the penetration by an intact liposomal form. 

PMID- 24277333
TI  - Antipyrine - new light on an old drug.
AB  - The time courses of analgesic activity of 4 different tablets containing
      different amounts of antipyrine were determined in 14 volunteers using electrical
      tooth pulp stimulation to elicit pain. Drug action was monitored by following
      somatosensory evoked potentials obtained from electroencephalographic
      measurements as well as pain rating and pain threshold determination. The results
      were compared with data obtained after administration of 1000 mg acetaminophen
      and two different doses of aspirin (500 and 1000 mg). At the same time drug
      concentration in saliva of the same volunteers was analyzed by quantitative in
      situ thin-layer-chromatography to investigate the pharmacokinetics. Furthermore,
      the in vitro drug release from the different tablets was studied with a
      continuous flow cell model. Antipyrine produced reliable analgesic activity. The
      onset of action was significantly faster than after administration of the same
      dose of aspirin, and the effect lasted longer than after intake of the same dose
      of acetaminophen. Comparison of the drug action and drug level in the body showed
      an excellent correlation between pharmacodynamics and pharmacokinetics. The study
      confirms our earlier findings on the value of somatosensory evoked potentials as
      a method to investigate the pharmacodynamics of weak analgesics in humans. The
      results also suggest to reconsider the use of antipyrine as an over-the-counter
      analgesic. 

PMID- 24277334
TI  - Prostaglandin E1-induced Catalepsy in the Rat: Role of Putative
      Neutrotransmitters.
AB  - Prostaglandin E1 (PGE1) produced dose-related catalepsy in rats when administered
      intracerebroventricularly. PGE1 induced catalepsy was significantly inhibited
      after pretreatment with pharmacological agents known to attenuate central
      serotonergic and cholinergic activity. It was also inhibited by PGF2alpha and
      naloxone. On the contrary, treatments enhancing central dopaminergic activity
      also reduced the cataleptic effect of PGE1. The results suggest that PGE1 induces
      catalepsy in rats by modulating activity of central neurotransmitters. 

PMID- 24277335
TI  - Morphine inhibition of theophylline clearance.
AB  - The effects of morphine on the single dose pharmacokinetics of theophylline were
      examined in two groups (6 rats/group) of male Sprague-Dawley rats after the
      administration of theophylline (6.25 mg/kg) alone and in conjunction with a 5 mg
      /kg I.V. dose of morphine sulfate. Concomitant morphine administration resulted
      in a 55 % reduction in theophylline clearance (0.14 +/- 0.04 vs. 0.31 +/- 0.061 .
      h(-1) kg(-1); p. < 0.0005). The reduction in theophylline clearance with morphine
      administration was accompanied by a significant prolongation in theophylline half
      life (3.5 +/- 1.5 vs. 1.4 +/- 0.35 h; p < 0.02). No changes in the volume of
      distribution of theophylline occurred with co-administration of morphine. The
      mechanism of this pharmacokinetic interaction may be partially related to
      competition between theophylline and morphine for enzymes which metabolize these
      compounds. 

PMID- 24277336
TI  - Delayed ethanol elimination in rats after application of cefamandole or
      cefoperazone.
AB  - Adult female Sprague-Dawley rats received ethanol (2 g/kg b.w., i.p.) 18 hours
      after pretreatment with the betalactam-antibiotics cefamandole (CMD) or
      cefoperazone (CPZ) (1 mmol/kg b.w. each, i.p.). The blood ethanol concentrations,
      determined repeatedly within 4 hours by head space GC, were increasingly elevated
      after CMD or CPZ up to twice the respective control values. The possible clinical
      and forensic significance of these findings for the therapeutic use of CMD or CPZ
      is pointed out. 

PMID- 24277337
TI  - Supporting people who care for adults with dementia.

PMID- 24277338
TI  - What will climate change mean for infectious disease?

PMID- 24277340
TI  - A patient with hypertrophic cardiomyopathy undergoing non-cardiac surgery.

PMID- 24277339
TI  - Predictors of suppurative complications for acute sore throat in primary care:
      prospective clinical cohort study.
AB  - OBJECTIVE: To document whether elements of a structured history and examination
      predict adverse outcome of acute sore throat. DESIGN: Prospective clinical
      cohort. SETTING: Primary care. PARTICIPANTS: 14,610 adults with acute sore throat
      (<= 2 weeks' duration). MAIN OUTCOME MEASURES: Common suppurative complications
      (quinsy or peritonsillar abscess, otitis media, sinusitis, impetigo or
      cellulitis) and reconsultation with new or unresolving symptoms within one month.
      RESULTS: Complications were assessed reliably (inter-rater kappa=0.95). 1.3%
      (177/13,445) of participants developed complications overall and 14.2%
      (1889/13,288) reconsulted with new or unresolving symptoms. Independent
      predictors of complications were severe tonsillar inflammation (documented among
      13.0% (1652/12,717); odds ratio 1.92, 95% confidence interval 1.28 to 2.89) and
      severe earache (5% (667/13,323); 3.02, 1.91 to 4.76), but the model including
      both variables had modest prognostic utility (bootstrapped area under the
      receiver operator curve 0.61, 0.57 to 0.65), and 70% of complications (124/177)
      occurred when neither was present. Clinical prediction rules for bacterial
      infection (Centor criteria and FeverPAIN) also predicted complications, but
      predictive values were also poor and most complications occurred with low scores
      (67% (118/175) scoring <= 2 for Centor; 126/173 (73%) scoring <= 2 for
      FeverPAIN). Previous medical problems, sex, temperature, and muscle aches were
      independently but weakly associated with reconsultation with new or unresolving
      symptoms. CONCLUSION: Important suppurative complications after an episode of
      acute sore throat in primary care are uncommon. History and examination and
      scores to predict bacterial infection cannot usefully identify those who will
      develop complications. Clinicians will need to rely on strategies such as safety
      netting or delayed prescription in managing the uncertainty and low risk of
      complications.

PMID- 24277341
TI  - Multi-modality organ-based approach to expected imaging findings, complications
      and recurrent tumour in the genitourinary tract after radiotherapy.
AB  - PURPOSE: Radiotherapy (RT) is an integral component in the management of many
      abdominal and pelvic malignancies. Imaging follow-up in patients who have
      received RT is performed to assess for treatment response, evaluate for tumour
      recurrence and to diagnose complications related to treatment. The purpose of
      this pictorial review is to depict the expected imaging findings and potential
      complications following RT in the genitourinary (GU) tract using an organ-based
      approach and to review the diagnosis of locally recurrent tumour in the GU tract
      following RT. CONCLUSIONS: Some GU malignancies, namely cervical and prostatic
      carcinoma, can be treated with radical RT with intent to cure. More frequently,
      the GU tract is indirectly treated as a result of RT to adjacent cancers.
      Expected imaging findings, RT-related complications and the diagnosis of
      recurrent tumour following RT in the GU tract often necessitate a multi-modality
      imaging approach, the incorporation of functional imaging techniques and an organ
      based approach for diagnosis.

PMID- 24277342
TI  - Therapeutic Strategies for Huntington's Disease.
AB  - Huntington's disease (HD) is a devastating autosomal dominant neurodegenerative
      disease, caused by expansion of the CAG repeat in the huntingtin (HTT) gene and
      characterized pathologically by the loss of pyramidal neurons in several cortical
      areas, of striatal medium spiny neurons, and of hypothalamic neurons. Clinically,
      a distinguishing feature of the disease is uncontrolled involuntary movements
      (chorea, dyskensias) accompanied by progressive cognitive, motor, and psychiatric
      impairment. This review focuses on the current state of therapeutic development
      for the treatment of HD, including the preclinical and clinical development of
      small molecules and molecular therapies. 

PMID- 24277344
TI  - Alcohol policies in industrial nations: Recent trends and alternative approaches.
AB  - Alcohol consumption and many alcohol-related problems have increased in most
      industrialized countries in the postwar period. The main societal responses have
      been increases in the treatment response to alcohol problems and in public and
      school education efforts. In the present era of fiscal crisis, there is also a
      trend toward punitive controls of the individual drinker. Potential policy
      alternatives should be broadened to include environmental protections for and
      from drunkenness, and a reconsideration of alcohol control strategies. Recent
      studies have shown that in some circumstances such laws have strong effects. 

PMID- 24277345
TI  - Practical issues, ethical concerns and future directions in the prevention of
      alcohol-related problems.
AB  - This article explores some basic assumptions that underlie the prevention of
      alcohol-related problems. Using a standard public health definition of
      prevention, the strategies of health promotion, disease prevention and health
      protection are explored along several dimensions. These dimensions are problem
      definition, ways of understanding the problem and ethical principles. The article
      argues for a broader definition of prevention based on a more holistic approach
      premised on the tenets of an ethical perspective linked to social justice. A
      general heuristic model for looking at relevant factors to be considered in the
      development of prevention research, planning and programming. 

PMID- 24277343
TI  - Small-molecule anticonvulsant agents with potent in vitro neuroprotection and
      favorable drug-like properties.
AB  - Severe seizure activity is associated with reoccurring cycles of excitotoxicity
      and oxidative stress that result in progressive neuronal damage and death.
      Intervention with these pathological processes is a compelling disease-modifying
      strategy for the treatment of seizure disorders. We have optimized a series of
      small molecules for neuroprotective and anticonvulsant activity as well as
      altered their physical properties to address potential metabolic liabilities, to
      improve CNS penetration, and to prolong the duration of action in vivo. Utilizing
      phenotypic screening of hippocampal cultures with nutrient medium depleted of
      antioxidants as a disease model, cell death and decreased neuronal viability
      produced by acute treatment with glutamate or hydrogen peroxide were prevented.
      Modifications to our previously reported proof of concept compounds have resulted
      in a lead which has full neuroprotective action at <1 nM and antiseizure activity
      across six animal models including the kindled rat and displays excellent
      pharmacokinetics including high exposure to the brain. These modifications have
      also eliminated the requirement for a chiral molecule, removing the possibility
      of racemization and making large-scale synthesis more easily accessible. These
      studies strengthen our earlier findings which indicate that potent,
      multifunctional neuroprotective anticonvulsants are feasible within a single
      molecular entity which also possesses favorable CNS-active drug properties in
      vitro and in vivo. 

PMID- 24277346
TI  - The 4-H youth organization: Primary prevention through competency promotion.
AB  - 4-H programs have as one of their major objectives primary prevention through
      competency enhancement of psychosocial development. To evaluate the program's
      effectiveness in enhancing psychosocial development, an evaluation study was
      completed. Questionnaire responses were obtained from 12, 13 and 14 year old
      adolescents and their parents. A total of 330 respondents (165 families)
      completed an assessment designed to measure psychosocial maturity. Comparisons
      between 4-H and non-4-H parental and youth responses indicated that 4-H
      involvement is associated with higher parental perceptions of interpersonal and
      social adequacy. Other analyses suggest age differences affecting social
      maturity, and rural versus urban residency differences in program effectiveness. 

PMID- 24277347
TI  - The Perceived Personal Control crisis intervention model in the prevention of
      emotional dysfunction for a high risk population of Caesarean Birth.
AB  - The Perceived Personal Control Model (PPC), a novel crisis intervention model for
      Ceasarean Birth (C/B) populations, is used at Rambam Medical Center by medical
      caregivers trained in the principles of the crisis intervention model. This model
      tackles risk factors in the environment by manipulating such situational
      variables as natural and organized support systems, information, sharing the
      decision making process, and developing task oriented activity geared to enhance
      emotional, cognitive, and behavioral control. The specific objective of the
      intervention model is to help the C/B mother to accomplish the specific
      psychological tasks. The general objective is to develop a prototype model for
      other high risk populations. The PPC model with respect to a C/B population is
      discussed. 

PMID- 24277348
TI  - The primary prevention of physician incompetence.

PMID- 24277349
TI  - The primary prevention of physician incompetence (or should it be
      ineffectiveness?).

PMID- 24277350
TI  - Prevention beacons illuminate safe spaces.

PMID- 24277351
TI  - Resourcefulness training for grandmothers: preliminary evidence of effectiveness.
AB  - In this pilot study of 102 grandmothers raising grandchildren, we used a quasi
      experimental, repeated measures design to examine effects of resourcefulness
      training reinforced by expressive writing (journaling) or verbal disclosure
      (digital voice recording) in reducing stress and depressive symptoms and
      enhancing quality of life. Resourcefulness training was compared with expressive
      writing, verbal disclosure, and attention control conditions. Both the expressive
      writing and verbal disclosure methods for reinforcing resourcefulness training
      were more effective than the other three conditions in reducing stress and
      depressive symptoms and improving quality of life. No difference was found
      between the two reinforcement methods. Grandmothers may benefit from learning
      resourcefulness skills and from practicing them in ways that best fit their needs
      and lifestyles.

PMID- 24277353
TI  - Reinvestigation of electric field-induced optical activity in alpha-quartz:
      application of a polarimeter with four photoelastic modulators.
AB  - Linear electrogyration (electric field-induced optical activity) and electro
      optic effects in x-cut and z-cut right-handed (RH) alpha-quartz were measured
      using a complete Mueller matrix polarimeter. The polarimeter used in the analysis
      was equipped with four photoelastic modulators operating at different
      frequencies. This configuration is especially sensitive due to the fidelity of
      the modulators and the fact that all the Mueller matrix elements can be delivered
      without any moving optical elements. The linear electrogyration coefficient
      gamma11 as a function of the wavelength of incident light was remeasured. The
      coefficient gamma33 , required by symmetry to be zero, was evaluated as a
      control. gamma11 was much smaller than values obtained previously using devices
      dependent on mechanical light modulation. Electrogyration measurements have often
      been confounded by the much larger linear electro-optic effect. The Mueller
      calculus used herein is well suited to the separation of the competing changes to
      the polarization state of light. Quadratic electrogyration associated with
      elements beta(11) and beta(33) was not detectable.

PMID- 24277355
TI  - Drug delivery by program or sensor controlled infusion devices.
AB  - The prolonged controlled administration of drugs could benefit the treatment of
      several diseases. In some instances variable delivery rates are required, e.g. in
      the treatment of diabetes. Program controlled externally portable devices and
      fixed rate implantable pumps are rapidly gaining clinical acceptance. Widespread
      use of the considerably more complex implantable devices with variable rates for
      use in diabetes therapy is hampered by the persistant problem of the
      incompatibility of insulin with the pump at body conditions. The ideal devices,
      feed-back controlled implants, cannot be realized since long-term implantable
      sensors, e.g. of glucose, are not yet available. Prospective clinical trials are
      running for all applications to clarify the cost-benefit-risk relationships. 

PMID- 24277354
TI  - Adenotonsillectomy and orthodontic therapy in pediatric obstructive sleep apnea.
AB  - PURPOSE: Rapid maxillary expansion (RME) is an additional treatment in pediatric
      obstructive sleep apnea (OSA). The aim of this study was to present data about
      the outcome of adenotonsillectomy (AT) and of RME in a clinical sample of
      pediatric OSA. METHODS: We consecutively enrolled children with OSA to undergo
      RME or AT. The age and the severity of OSA are the main factors involved in the
      choice of treatment. A polysomnography was performed at the baseline (i.e.,
      before treatment, T0) and 1 year after treatment (T1). RESULTS: A total of 52
      subjects fulfilled the inclusion criteria. Twenty-five children underwent AT
      (group 1) and 22 children underwent RME (group 2). Five children underwent both
      treatments (group 3). Children in group 2 were older, had a longer disease
      duration, a higher body mass index (BMI), a lower apnea-hypopnea index (AHI), and
      a lower arousal index at T0 than children in group 1. After 1 year, BMI
      percentile and overnight mean saturation increased in group 1 while AHI and
      arousal index decreased. In group 2, mean overnight saturation increased while
      AHI decreased. Children in group 3 displayed a significant decrease in AHI from
      T0 to T1. CONCLUSIONS: Our data demonstrate that both treatments help to improve
      OSA, and a multidisciplinary approach to treatment is suggested.

PMID- 24277352
TI  - Up-regulation of Gadd45alpha after exposure to metal nanoparticles: the role of
      hypoxia inducible factor 1alpha.
AB  - The increased development and use of nanoparticles in various fields may lead to
      increased exposure, directly affecting human health. Our current knowledge of the
      health effects of metal nanoparticles such as cobalt and titanium dioxide (Nano
      Co and Nano-TiO2 ) is limited but suggests that some metal nanoparticles may
      cause genotoxic effects including cell cycle arrest, DNA damage, and apoptosis.
      The growth arrest and DNA damage-inducible 45alpha protein (Gadd45alpha) has been
      characterized as one of the key players in the cellular responses to a variety of
      DNA damaging agents. The aim of this study was to investigate the alteration of
      Gadd45alpha expression in mouse embryo fibroblasts (PW) exposed to metal
      nanoparticles and the possible mechanisms. Non-toxic doses of Nano-Co and Nano
      TiO2 were selected to treat cells. Our results showed that Nano-Co caused a dose-
      and time-dependent increase in Gadd45alpha expression, but Nano-TiO2 did not. To
      investigate the potential pathways involved in Nano-Co-induced Gadd45alpha up
      regulation, we measured the expression of hypoxia inducible factor 1alpha (HIF
      1alpha) in PW cells exposed to Nano-Co and Nano-TiO2 . Our results showed that
      exposure to Nano-Co caused HIF-1alpha accumulation in the nucleus. In addition,
      hypoxia inducible factor 1alpha knock-out cells [HIF-1alpha (-/-)] and its wild
      type cells [HIF-1alpha (+/+)] were used. Our results demonstrated that Nano-Co
      caused a dose- and time-dependent increase in Gadd45alpha expression in wild-type
      HIF-1alpha (+/+) cells, but only a slight increase in HIF-1alpha (-/-) cells. Pre
      treatment of PW cells with heat shock protein 90 inhibitor, 17-(Allylamino)-17
      demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Co significantly
      abolished Nano-Co-induced Gadd45alpha expression. These results suggest that HIF
      1alpha accumulation may be partially involved in the increased Gadd45alpha
      expression in cells exposed to Nano-Co. These findings may have important
      implications for understanding the potential health effects of metal nanoparticle
      exposure.

PMID- 24277356
TI  - Effect of column temperature and eluent flow rate on the high performance liquid
      chromatographic analysis of cyclosporin a and d.
AB  - On a reversed-phase C18 analytical column using an eluent of 70:30 acetonitrile
      and water, the following effects were observed with increasing column temperature
      (from 25 to 75 degrees C) for Cyclosporin A (CSA) and Cyclosporin D (CSD). The
      peak heights and number of theoretical plates (N) increased. The height
      equivalent to a theoretical plate (HETP) decreased. The areas under the peaks,
      retention times and capacity factors (k') for both compounds did not vary with
      temperature. With increasing eluent flow rate (from 0.5 to 2.5ml/ min), the peak
      heights, peak areas, retention times and N all decreased for both compounds. A
      slight decrease in k' for CSA and CSD was also observed. HETP increased with
      increasing flow. The separation factor, alpha, remained relatively constant for
      the ranges of temperatures and flow rates investigated. 

PMID- 24277358
TI  - Effect of Entrapped Markers on the in situ Jejunal Uptake from Liposomal Systems.
AB  - The effect of entrapped PEG-4000, inulin, and insulin on thein situuptake from
      the rat jejunum of liposomes was determined. Each of these markers greatly
      reduced or completely eliminated jejunal uptake unless the liposomes were
      repeatedly "washed" to remove marker from the external bilayer surface. Addition
      of free marker to a suspension of empty liposomes resulted in complete loss of
      liposomal uptake. It appears that "inert" markers can profoundly affect the rate
      and extent of liposomal uptake from the rat jejunum and the preparative technique
      employed can greatly affect the behavior of the system. 

PMID- 24277357
TI  - The hypolipidemic activity of 3-iminophthalimidine in rodents.
AB  - 3-Immophthalimidine (3-imino-2,3-dihydroisoindol-l-one) was examined for its
      hypolipidemic activity in rodents as a chemical modification of the phthalimide
      nucleus. Administration of 3-iminophthalimidine for 16 days, at 20 mg/kg/day,
      demonstrated potent hypolipidemic activity, decreasing serum cholesterol and
      triglyceride levels by 44 % and 41 %, respectively. No effects on organ or body
      weight, or food consumption were noted as a result of administration of this
      agent to rats. However, reductions of liver lipid levels, i. e., triglycerides
      and neutral lipids, as well as lipid content of serum lipoprotein fractions, i.
      e., cholesterol, triglyceride and neutral lipids, were observed following
      administration of this agent. An increase was noted in fecal excretion of
      cholesterol and/or its metabolites. This effect was not correlated with an
      increase in bile acid synthesis, but may due in part to increased biliary
      excretion of cholesterol. Significant inhibitory effects of 3-iminophthalimidine
      on liver enzyme activities were noted, including acetyl CoA carboxylase and sn
      glycerol-3-phosphate acyl transferase. Mitochondrial citrate exchange was also
      greatly reduced at low concentrations of the agent. Inhibition at these sites
      could account for the reduction in serum triglyceride levels observed after
      treatment in rodents. 

PMID- 24277359
TI  - Relationship of octanol/water partition coefficient and molecular weight to
      cellular permeability and partitioning in s49 lymphoma cells.
AB  - We have used modified standard methods and derived new formulae to quantitate
      cell permeability (P), cell/media partitioning (lambda), and intracellular
      sequestration or binding rate constants (m) for cultured S49 murine lymphoma
      cells in suspension. Using 15 standard compounds and anticancer drugs, we found
      quantitative relationships among log P, log PO (octanol/pH 7.4 buffer partition
      coefficient), and molecular weight (MW) such that logP = -4.5 + 0.56log (PO(MW)(
      1/2)). A good correlation among P, lambda, and MW was also determined with lambda
      = 0.67 + 5890 gm(1/2) cm(-1) sec (P (MW)(1/2)). These studies show that there is
      a strong partitioning (lambda) dependence to molecular weight and permeability
      that can be predicted even for known carrier-transported and biotransformable
      compounds. Furthermore, results of this study show that the slope of the plot of
      permeability and lipophilicity is not necessarily unity as has been postulated
      from the results of other studies. 

PMID- 24277360
TI  - Hypolipidemic Agents of Phthalimide Derivatives 6. Effects of Aromatic vs. Non
      Aromatic Imides.
AB  - A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and
      glutarimide derivatives demonstrated significant hypolipidemic activity at 20
      mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be
      the most potent analogue of the new compounds, lowering serum triglyceride levels
      51 % and serum cholesterol 47 % after 16 days dosing in mice. For the N
      substituted derivatives, i. e., n-butyl, butanone, and propionic acid, of these
      four cyclic imides, there appeared to be no obvious trend in ability to reduce
      serum lipid levels. In general, the 1,8-naphthalimide and glutarimide derivatives
      appeared to be less active than phthalimide and succinimide. However, the alpha
      phenylsuccinimide afforded less activity than the alpha-phenylglutarimide. Most
      of the derivatives at 20mg/kg/day demonstrated improved activity over clofibrate
      at 150mg/kg/day. 

PMID- 24277361
TI  - In vitro antimicrobial activity of benzoquinolinediones.
AB  - The in vitro antibacterial and anti-fungal activity of benz[g]isoquinoline-5,10
      dione (1), benzo[g]quinoline-5, 10-dione (2), benzo[g]quinoline-5,6-dione (3),
      and anthraquinone (4) was determined using the agar well-diffusion assay. The
      minimum inhibitory concentrations (MIC's) of each of the active compounds (1-3)
      was determined using the two-fold serial dilution technique. Of the four
      compounds tested, benz[g]isoquinoline-5,10-dione exhibited the best overall
      activity against both bacteria and fungi. Particularly noteworthy was its
      significant antifungal activity which was comparable to the activity of the
      standard antifungal antibiotic amphotericin B. 

PMID- 24277362
TI  - Phosphorus GABA Analogues as Potential Prodrugs.
AB  - Analogues of gamma-aminobutyric acid (GABA), wherein a P=O moiety is separated by
      three carbon atoms from an amino group, were incorporated into Schiff bases as
      potential acid-labile carrier molecules. These include 3-aminophenylphosphonic
      acid, its dimethyl ester and its previously unreported N,N'
      diisopropylphosphonodiamide. A benzophenone derivative of GABA was also
      synthesized.A study of the degrees of in vitro hydrolysis of four Schiff bases
      indicated that lability of the C=N bond is determined by electronic influences of
      ring substituents.All new products were tested for abilities to inhibit maximal
      electroshock- and subcutaneous pentylenetetrazol (Metrazol)-induced seizures in
      mice.Activity was found only in the former system with moderate inhibition
      displayed by two dimethyl ester and the GABA Schiff bases. 

PMID- 24277363
TI  - In vitro Metabolism of Bumetanide.
AB  - A new metabolite of the diuretic drug bumetanide, the 4-[(4'-hydroxy)-phenoxy]
      analog (7), was identified in incubation mixtures of rat liver microsomes.
      Phenobarbital and clofibrate pretreatment to induce microsomal enzymes changed
      the relative amounts of the six metabolites formed. Compound 7was the most
      prevalent metabolite after clofibrate pretreatment. 

PMID- 24277364
TI  - Replacing the Mixed Function Oxidase N-Demethylation by Hydrogen Peroxide and
      either Hemoglobin or Ferrous Sulfate.
AB  - Formaldehyde liberated from N-demethylation of aminopyrine, N-methyl-piperazine
      and from the optically active (+)-and (-)-ephedrine was quantitated from the
      incubation mixtures of hepatic microsomes and from reactions of hydrogen peroxide
      with either hemoglobin or ferrous sulfate. Stereoselectivity was observed only in
      incubations with hepatic microsomes. N-Formyl derivatives were isolated from the
      reactions of N-ethylmorpholine, aminopyrine, N-methylpiperazine and N,N'-dimethyl
      piperazine with ferrous sulfate and hydrogen peroxide (Fenton reagent). Electron
      withdrawing groups (NH, NCH3, O) at the fourth position to the N-alky! group
      facilitate N-dealkylation with Fenton reagent. 

PMID- 24277365
TI  - Effect of mangiferin, a naturally occurring glucosylxanthone, on reproductive
      function of rats.
AB  - Female albino rats, treated with mangiferin at daily doses of 5 mg/100 g ip for 3
      days during mid-gestation, showed complete fetal resorption. Administration of a
      mangiferin-Cu(2+) (1:1) complex, along with mangiferin, attenuated the effect of
      mangiferin and restored the completion of gestation in 60% of the rats. The
      mother rats that completed gestation successfully did not show any post-natal
      abnormality, and the litters born were also normal. Mangiferin treatment of non
      gestating female rats caused little or no changes in their organ weights.
      However, changes in the protein and protein-DNA ratios of several organs were
      statistically significant. Mangiferin also modified the ascorbic acid retention
      capacity of adrenal glands of male rats in vitro. These findings are appraised in
      view of mangiferin as a potential antifertility agent. 

PMID- 24277368
TI  - Recent research on the family at adolescence: The extent and nature of sex
      differences.

PMID- 24277370
TI  - Disagreements about rules in families with seventh-grade girls and boys.
AB  - Parental reports of disagreements and serious disagreements about rules were
      examined in 200 families with seventh-grade boys and girls. No gender differences
      were found: Mothers did not report more disagreements than fathers; no more
      disagreements were reported for girls than boys. Disagreements about personal
      habits and family obligations were more common than disagreements about peer
      relations. Disagreements and serious disagreements, in general, were
      significantly correlated (positively) with parental reports of child
      oppositionalism and (negatively) with parents' satisfaction with parenting the
      target child, although some dyadic differences were found. Children's reports of
      parental acceptance were negatively correlated with disagreements only for the
      father-daughter dyad. Support was found for some of Baumrind's ([1968]
      "Authoritarian vs. Authoritative Control,"Adolescence 3: 255-272) notions
      regarding relations between rule frequency, child participation in rule making,
      and disagreements about rules, especially for the father-daughter dyad. 

PMID- 24277369
TI  - Sex differences within the family: Studies of adolescent and parent family
      interactions.
AB  - Sex differences in verbal family interactions were investigated in a group of 79
      adolescents and parents from normal and psychiatric settings. The analyses were
      designed to study these differences in both generations, parent and adolescent.
      Parent and adolescent interactions with one another were observed in a
      semistructured, revealed-differences family discussion. All of the individual
      speeches were then scored with our Constraining and Enabling Coding System
      (CECS). Initial predictions involved both adolescent and parent differences.
      These hypotheses were only partially confirmed. The strongest findings pertained
      to parent sex differences, as we found strikingly higher levels of cognitive
      enabling speeches expressed by fathers and significantly more speeches addressed
      to fathers. We discuss several alternative interpretations of these findings.
      Perspectives included in our considerations are direction of effect and
      influences of task/context upon the expression of family sex differences. 

PMID- 24277371
TI  - Gender issues in the interface of family experience and adolescents' friendship
      and dating identity.
AB  - This study focuses on the role of family experience in adolescents' conception of
      the self in the context of friendship and dating relationships. Three issues are
      addressed: the extent of sex differences in adolescents' friendship and dating
      identity, how links between family experience and friendship and dating identity
      might differ for males and females, and whether mothers and fathers play
      distinctive roles in such development. A sample of Caucasian two-parent families,
      each including an adolescent who was a high school senior, was observed in a
      family interaction task designed to elicit the expression and coordination of a
      variety of points of view. Each adolescent was also given an interview assessing
      exploration and commitment in friendship and dating identity. Only one sex
      difference was found in identity, with females more committed in their
      conceptions of dating relationships than males. The key finding of the study
      concerns the distinctive patterns of family interaction associated with
      friendship and dating identity. For females, separateness in family interaction
      was related to their friendship identity exploration, whereas for males, the
      links between family interaction and exploration all involved connectedness. The
      different contingencies may reflect the interplay between different societal
      patterns of support and restriction of males' and females' exploration. 

PMID- 24277372
TI  - Communication and connectedness in mother- and father-adolescent relationships.
AB  - In Study 1, 605 adolescents estimated how well their parents knew them and said
      how much they cared what their parents thought about them. Sons and daughters
      judged that mothers knew them fairly well, but daughters judged that fathers did
      not know them so well. At the same time, statements of caring indicated high
      concern by sons and daughters for both parents. A supplemental result was that
      sons from white-collar families gave relatively low estimates of how much their
      mothers knew them and daughters from blue-collar families gave very low estimates
      of how much their fathers knew them. In Study 2, 52 adolescents from single
      parent families and living with their mothers but not with their fathers also
      gave estimates for knowing and caring. Knowing followed the above pattern, with
      an expected lowering of estimates for fathers by sons and daughters. Further,
      estimates of caring declined especially for fathers by daughters. These results
      add to the growing literature that shows mother-adolescent and father-adolescent
      relationships contribute differentially to psychological development. The results
      seem especially relevant for adolescents' sex role development and constructed
      individuality as mediated through relationships with both parents. 

PMID- 24277373
TI  - Fathers, mothers, and adolescents: Gender-based differences in parental roles
      during adolescence.
AB  - This study examined the involvement and satisfaction of adolescents with their
      fathers and mothers. Possible age and sex differences were investigated for three
      components of involvement: proportion of time spent with fathers and mothers,
      type of activities engaged in, and degree of satisfaction with those activities.
      Telephone interviews were used to obtain information about previous day's
      activities from 61 adolescents in grades 6-12. For each activity, data were
      obtained on duration, who else was present, and satisfaction. Results indicated
      that adolescents spent a greater proportion of time in leisure than in work with
      fathers, and equal time in work and in leisure with mothers. In general,
      adolescents were as satisfied with activities with their fathers as with their
      mothers. Adolescents enjoyed working with fathers more than mothers, however. The
      results demonstrate that activity satisfaction varies as a function of what
      activities adolescents engage in and who is present. 

PMID- 24277374
TI  - Adolescent autonomy, parent-adolescent conflict, and parental well-being.
AB  - The present study examines whether parents' reports of well-being are related to
      the level of parent-adolescent conflict in the family and their youngsters' level
      of emotional autonomy. The sample is composed of 129 intact families with a first
      born child between the ages of 10 and 15. Measures included parents' reports of
      midlife identity concerns, self-esteem, life satisfaction, psychological
      symptoms, and parent-adolescent conflict, as well as youngsters' reports of
      emotional autonomy vis-a-vis parents. Findings indicate that (1) parents'
      experience of midlife identity concerns is positively related to the level of
      emotional autonomy reported by same-sex children; (2) mothers', but not fathers',
      well-being is negatively related to the intensity of parent-adolescent conflict;
      and (3) socioeconomic status moderates the relation between parental well-being
      and parent-adolescent relations. These results are discussed in terms of
      psychoanalytic and parental stress perspectives on parental well-being during the
      adolescent years. 

PMID- 24277375
TI  - Quantitative assessment of the association between XPC Lys939Gln polymorphism and
      cutaneous melanoma risk.
AB  - Previous studies evaluating the association between XPC Lys939Gln polymorphism
      and cutaneous melanoma risk reported conflicting findings. We searched PubMed and
      Embase databases up to May 16, 2013 to identify eligible studies on the
      association between XPC Lys939Gln polymorphism and cutaneous melanoma risk.
      Finally, a total of seven case-control studies including 3,971 cases of cutaneous
      melanoma and 5,873 controls were included in the meta-analysis. Statistical
      analysis was performed with STATA version 11.0. Odds ratios (ORs) with 95 %
      confidence intervals (95 % CIs) were used to assess the strength of the
      association. Overall, there was no association between XPC Lys939Gln polymorphism
      and cutaneous melanoma risk under all five genetic models (Gln vs. Lys: OR =
      1.11, 95 % CI = 0.98-1.26, P = 0.10; GlnGln vs. LysLys: OR = 1.26, 95 % CI = 0.98
      1.61, P = 0.07; LysGln vs. LysLys: OR = 1.04, 95 % CI = 0.88-1.22, P = 0.64;
      GlnGln/LysGln vs. LysLys: OR = 1.10, 95 % CI = 0.92-1.31, P = 0.29; GlnGln vs.
      LysLys/LysGln: OR = 1.19, 95 % CI = 0.99-1.43, P = 0.06). Subgroup analysis in
      Caucasians showed that there was an obvious association between XPC Lys939Gln
      polymorphism and cutaneous melanoma risk in Caucasians (GlnGln vs. LysLys/LysGln:
      OR = 1.12, 95 % CI = 1.00-1.25, P = 0.05). Sensitivity analysis by omitting one
      study in turns showed that the significance of the pooled ORs was not stable. In
      addition, there was some evidence of publication bias in the meta-analysis, and
      meta-analyses of the studies with large sample size did not find the obvious
      association between XPC Lys939Gln polymorphism and cutaneous melanoma risk in
      Caucasians. Therefore, there is little evidence for the association between XPC
      Lys939Gln polymorphism and cutaneous melanoma risk.

PMID- 24277376
TI  - Significant associations between X-ray repair cross-complementing group 3 genetic
      polymorphisms and thyroid cancer risk.
AB  - Polymorphisms in X-ray cross-complementing group 3 (XRCC3) are proposed to be
      associated with cancer susceptibility, but previous studies on the associations
      between XRCC3 polymorphisms and thyroid cancer are controversial. We performed a
      systemic review and meta-analysis to investigate the associations of XRCC3
      polymorphisms with thyroid cancer risk. We used odds ratio (OR) with 95 %
      confidence interval (95%CI) to assess the associations. For XRCC3 C241T
      polymorphism, meta-analysis of total eligible studies showed that there was no
      association between XRCC3 C241T polymorphism and thyroid cancer risk, but
      subgroup analysis in Caucasians showed that there was a significant association
      between XRCC3 C241T polymorphism and thyroid cancer risk (T versus C: OR = 1.30,
      95%CI 1.05-1.62, P = 0.01; TT versus CC: OR = 1.74, 95%CI 1.13-2.70, P = 0.01; TT
      versus CC/CT: OR = 1.74, 95%CI 1.16-2.60, P = 0.007). For XRCC3 A17893G
      polymorphism, meta-analysis of total eligible studies showed that there was an
      obvious association between XRCC3 A17893G polymorphism and thyroid cancer risk
      (GG versus AA/AG: OR = 0.57, 95%CI 0.35-0.93, P = 0.02), but subgroup analysis by
      ethnicity only identify the significant association in Asians. In summary, the
      meta-analysis suggests that there are significant associations of XRCC3
      polymorphisms with thyroid cancer risk. Besides, more studies with large sample
      sizes are needed to further assess the associations above.

PMID- 24277377
TI  - Aurora-A: a potential DNA repair modulator.
AB  - It is well-known that overexpression of Aurora-A promotes tumorigenesis, but the
      role of Aurora-A in the development of cancer has not been fully investigated.
      Recent studies indicate that Aurora-A may confer cancer cell chemo- and
      radioresistance through dysregulation of cell cycle progression and DNA damage
      response. Direct evidences from literatures suggest that Aurora-A inhibits pRb,
      p53, p21(waf1/cip1), and p27(cip/kip) but enhances Plk1, CDC25, CDK1, and cyclin
      B1 to repeal cell cycle checkpoints and to promote cell cycle progression. Other
      studies indicate that Aurora-A suppresses BRCA1, BRCA2, RAD51, poly(ADP ribose)
      polymerase (PARP), and gamma-H2AX to dysregulate DNA damage response. Aurora-A
      may also interact with RAS and Myc to control DNA repair indirectly. In this
      review, we summarized the potential role of Aurora-A in DNA repair from the
      current literatures and concluded that Aurora-A may function as a DNA repair
      modulator to control cancer cell radio- and chemosensitivity, and that Aurora-A
      associated DNA repair molecules may be considered for targeted cancer therapy. 

PMID- 24277378
TI  - Abnormal expression of FLOT1 correlates with tumor progression and poor survival
      in patients with non-small cell lung cancer.
AB  - Recent studies have revealed that flotillin-1 (FLOT1) plays important roles in
      cancer progression. However, the role of FLOT1 in development and progression of
      non-small cell lung cancer (NSCLC) remains largely unknown. The objective of the
      current study was to investigate the expression pattern and clinicopathological
      significance of FLOT1 in patients with NSCLC. Real-time quantitative polymerase
      chain reaction was applied to examine FLOT1 mRNA expression in 52 pairs of NSCLC
      tissues and adjacent noncancerous tissues. Immunohistochemistry was performed to
      examine FLOT1 protein expression in paraffin-embedded tissues from 106 NSCLC
      patients. Statistical analyses were applied to evaluate the diagnostic value and
      associations of FLOT1 expression with clinicopathological characteristics. FLOT1
      mRNA expression was evidently upregulated in NSCLC tissues compared with that in
      the adjacent noncancerous tissues. In the 106 cases of tested NSCLC samples,
      FLOT1 protein level was positively correlated with tumor size, tumor stage, and
      lymph node metastasis. Patients with higher FLOT1 expression had shorter overall
      survival time, whereas those with lower FLOT1 expression had longer survival
      time. Taken together, our findings indicate that FLOT1 may play an important role
      in NSCLC tumorigenesis. Further elucidation of the molecular mechanisms
      underlying the role of FLOT1 is warranted. 

PMID- 24277379
TI  - Combining transarterial chemoembolization with radiofrequency ablation for
      hepatocellular carcinoma.
AB  - The aim of this study was to compare the effectiveness of combination of
      radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) with
      that of RFA alone in patients with hepatocellular carcinoma (HCC). All possible
      trials comparing RFA plus TACE with RFA alone for HCC were included into this
      meta-analysis. We estimated the summary odds ratio (OR) with its 95% confidence
      interval (95% CI) to assess the effects. Nineteen eligible studies matched the
      selection criteria, including 1,728 patients. Meta-analysis showed that the
      combination of TACE and RFA (OR(1 year) = 2.14, 95% CI = 1.57-2.91, P < 0.001;
      OR(3 years) = 1.98, 95% CI = 1.28-3.07, P = 0.001; OR(5 years) = 2.70, 95% CI =
      1.42-5.14, P = 0.003) were associated with higher survival rates. No evidence of
      publication bias was observed. High-quality evidence suggests that TACE plus RFA
      improve the survival rates compared with RFA alone for patients with HCC.

PMID- 24277380
TI  - Diagnosis and management of hyperhidrosis.

PMID- 24277381
TI  - Bayesian estimation of multinomial processing tree models with heterogeneity in
      participants and items.
AB  - Multinomial processing tree (MPT) models are theoretically motivated stochastic
      models for the analysis of categorical data. Here we focus on a crossed-random
      effects extension of the Bayesian latent-trait pair-clustering MPT model. Our
      approach assumes that participant and item effects combine additively on the
      probit scale and postulates (multivariate) normal distributions for the random
      effects. We provide a WinBUGS implementation of the crossed-random effects pair
      clustering model and an application to novel experimental data. The present
      approach may be adapted to handle other MPT models. 

PMID- 24277382
TI  - Towards efficient use of research resources: a nationwide database of ongoing
      primary care research projects in the Netherlands.
AB  - PURPOSE. Although in the last decades primary care research has evolved with
      great success, there is a growing need to prioritize the topics given the limited
      resources available. Therefore, we constructed a nationwide database of ongoing
      primary care research projects in the Netherlands, and we assessed if the
      distribution of research topics matched with primary care practice. METHODS: We
      conducted a survey among the main primary care research centres in the
      Netherlands and gathered details of all ongoing primary care research projects.
      We classified the projects according to research topic, relation to professional
      guidelines and knowledge deficits, collaborative partners and funding source.
      Subsequently, we compared the frequency distribution of clinical topics of
      research projects to the prevalence of problems in primary care practice.
      RESULTS: We identified 296 ongoing primary care research projects from 11
      research centres. Most projects were designed as randomized controlled trial
      (35%) or observational cohort (34%), and government funded mostly (60%).
      Thematically, most research projects addressed chronic diseases, mainly
      cardiovascular risk management (8%), depressive disorders (8%) and diabetes
      mellitus (7%). One-fifth of the projects was related to defined knowledge
      deficits in primary care guidelines. From a clinical primary care perspective,
      research projects on dermatological problems were significantly underrepresented
      (P = 0.01). CONCLUSIONS: This survey of ongoing projects demonstrates that
      primary care research has a firm basis in the Netherlands, with a strong focus on
      chronic disease. The fit with primary care practice can improve, and future
      research should address knowledge deficits in professional guidelines more.

PMID- 24277383
TI  - Referring advanced cancer patients for palliative treatment: a national
      structured vignette survey of Australian GPs.
AB  - BACKGROUND: Although (general practitioners) GPs have a role in managing patients
      with advanced cancer, little is known about their referral decisions. AIM: The
      aim of this study was to explore, using structured vignettes, how GPs might
      manage patients presenting with advanced cancer. DESIGN: A self-administered
      survey consisting of structured vignettes was administered to GPs in Australia.
      Fifty-six vignettes describing patients who may benefit from palliative care
      and/or treatment were constructed encompassing seven advanced cancer diagnoses
      (cerebral metastasis, lung metastases, renal cancer, bone metastases, ulcerating
      skin metastases, spinal metastases and stridor) and three clinical variables
      (age, prognosis and mobility). Seven vignettes were presented to each respondent.
      Respondents were asked if they would refer the patient and the benefits of
      different treatment modalities. Participant responses were compared with
      responses provided by an expert panel. Logistic regression and parametric tests
      were used to estimate odds of referral. SETTING/PARTICIPANTS: The respondents
      were GPs, currently registered and practicing in Australia. Participants were
      selected randomly from a national list of practitioners. RESULTS: Four hundred
      and seven questionnaires were received. There was wide variation (31%-97%) in the
      proportion of respondents who agreed with the expert panel. The odds of referral
      for radiotherapy varied the most. Significant predictive variables included
      patient age, mobility and prognosis and respondent demographics. CONCLUSION: GPs'
      referral decisions for patients with advanced cancer appear to deviate from
      expert opinion and can be predicted using respondent and patient characteristics.
      If these data were reflected in clinical practice some patients may not be
      offered helpful palliative treatment options.

PMID- 24277384
TI  - Stepped collaborative depression care: primary care results before and after
      implementation of a stepped collaborative depression programme.
AB  - BACKGROUND: Numerous intensive research projects to assess the effects of stepped
      collaborative care (SCC) for depressed patients have been reported in primary
      care, yet it is unclear how SCC is sustained in usual care. OBJECTIVE: To assess
      how SCC for depression is actually being used and how it performs in usual
      primary care by studying medical data that are routinely collected in family
      practice, outside the research setting. METHODS: Retrospective before and after
      comparison of electronic medical records (EMR) regarding the implementation of an
      SCC depression programme in a large primary care organization from 2003 to 2012.
      Depression care parameters included prevalences, minimal interventions, Beck
      Depression Inventory-2 (BDI-2), antidepressants, referrals to psychologists and
      psychiatrists and primary health care consumption. RESULTS: After programme
      implementation, differentiation between levels of depression severity increased,
      more patients were treated with minimal interventions and more patients were
      monitored with BDI-2. These effects occurred in both nonseverely and severely
      depressed patients, although they were larger for patients registered as
      nonseverely depressed. Antidepressant prescription rates and referral rates
      seemed not to have been influenced by the SCC programme. Health care consumption
      of the depressed patients increased significantly. CONCLUSIONS: The depression
      care parameters changed to a different extent and at a different pace than after
      previous implementation initiatives. Future research should identify whether SCC
      uptake in primary care is best enhanced by intensive external guidance or by
      making care providers themselves responsible for the implementation. Analyses of
      EMR can be valuable in monitoring the implementation effects, especially after
      research projects are completed.

PMID- 24277385
TI  - Evaluation of a social support program for young unwed mothers.
AB  - This research evaluated the effects of a social support program on young unwed
      mothers. Measures of social support, stress, affect, and life events were
      compiled by 15 program participants and 15 matched controls before and after the
      program six months later. The results showed significant increases in the size of
      the family and friend network for program participants relative to controls.
      Also, program participants reported more involvement in work and school and
      maintained a high level of positive affect significantly more than controls. The
      two groups did not differ in reported levels of stress. The implications of the
      findings for future research and program development were discussed. 

PMID- 24277386
TI  - Effects of preventive cognitive self-instruction training on adolescent
      attitudes, experiences, and state anxiety.
AB  - The effects of teacher-directed cognitive self-instruction (TI) were compared
      with an instructions-only component control condition (IO) in order to examine
      the former's efficacy as a primary prevention strategy. In a quasi-experimental
      design. two intact high school psychology classes were randomly assigned to
      either TI or IO. Each condition lasted for eight 45-minute class periods, and
      each group was given an in vivo homework assignment. Pretreatment equivalence and
      demand analyses yielded no evidence of differences. Results of a posttreatment
      measure of attitude toward treatments and a pre- and posttreatment measure of
      state anxiety suggested that trainerdirected cognitive self-instruction may be a
      promising primary prevention strategy. 

PMID- 24277387
TI  - An expanded view of respite care: Supporting families.
AB  - Respite care services are in a unique position to provide a family-oriented,
      ecological, preventive perspective to child placement practices by meeting family
      crisis needs, developing networks of social supports, and preventing permanent
      separation of family members. An expanded view of respite care which includes (1)
      respite care for the family of the disabled child, (2) respite care for the
      internally stressed family/at risk child, and (3) respite care for the externally
      stressed family is proposed. 

PMID- 24277388
TI  - Local public record data: A rape crisis center tool for program planning and
      intervention.
AB  - This paper demonstrates the use of local public record data by a rape crisis
      center for program planning and intervention in the area of rape prevention.
      While a number of national studies describe victim and offender characteristics
      and cirsumstances of rape, these studies may be inappropriate for local planning
      efforts due to the lack of generalizability of national or regional statistics to
      local populations. Local data, available from easily accessed police and court
      records provide immediate and relevant information for local needs.Community rape
      data from the years 1977-1979 are described. Examples are presented which detail
      the use of local data by a rape crisis center to: enhance educational programs,
      target populations most needing victim services, improve program planning and
      volunteer training, facilitate intervention strategies with the police and court
      systems, and provide information for social service planning and advocacy.Issues
      related to data collection are discussed, and the use of public record data by
      other grass-roots victim services such as spouse-abuse and elder-abuse prevention
      services is advocated. 

PMID- 24277389
TI  - Preventing cigarette smoking with youth.
AB  - A repeated measures, control group design compared skills-building with attitude
      modification approaches to prevent cigarette smoking of 234 sixth graders.
      Subjects in a skills-building condition, more than those in an attitude
      modification condition or in a control condition, had better posttest scores on
      cognitive and interpersonal precursors of nonsmoking. Greater pretest to posttest
      changes in cigarette use were reported for attitude modification condition
      subjects than for skills-building and control condition subjects. Compared with
      attitude modification and control condition subjects, skills-building condition
      subjects had lower reported increases in cigarette use from posttest to 6 months
      and from 6 to 12 months. 

PMID- 24277391
TI  - Primary Prevention Program Clearinghouse Psychology Department-Dewey Hall
      University of Vermont, Burlington, VT 05405.

PMID- 24277390
TI  - A giant figure in prevention history.

PMID- 24277392
TI  - [Application of immune nutrition in patients with gastrointestinal tumors].
AB  - Immune nutrition refers to adding some special nutrients to the standard formula
      of nutrition in order to treat and regulate metabolism and immune function by its
      pharmacological effect. In recent years, immune nutrition, including glutamine,
      arginine, omega-3 PUFA, nucleotide etc, has been widely used in patients with
      gastrointestinal cancer. These nutrients show their different supporting
      functions through different mechanisms, and improve the clinical outcome of
      patients. Therefore, clinical nutrition has been expanded and upgraded from the
      traditional "nutrition" to "nutritional therapy". 

PMID- 24277393
TI  - [Perioperative management of the pancreaticoduoden-ectomy: fluid administration
      and nutritional support based on complication prevention and treatment].
AB  - Pancreaticoduodenectomy(PD) has been widely accepted as one of the most
      complicated operation in abdominal surgery. The patients who receive PD operation
      always have other concurrent conditions, such as jaundice, diabetes, liver
      dysfunction, and malnutrition. Pancreatic fistula, biliary fistula and
      gastrointestinal dysfunction are common complications after PD. Proper
      perioperative management and fluid administration can reduce postoperative
      complications and the mortality. 

PMID- 24277394
TI  - [Details of enteral nutrition for gastric carcinoma patients].
AB  - Enteral nutrition can provide adequate nutrients and enhance immunity. Because it
      is inexpensive, no significant side effects, and convenient, enteral nutrition
      has been used widely. However, enteral nutrition has its limitation, therefore
      some details should be noticed during the management. In this paper, we discuss
      the details about enteral nutrition based on the data of our gastric carcinoma
      patients. 

PMID- 24277395
TI  - [Nutritional support therapy in patients with liver dysfunction undergoing
      gastrointestinal surgery].
AB  - Liver dysfunction by various reasons can cause metabolic disorders of a variety
      of nutrients and malnutrition, while malnutrition affects the recovery of liver
      function. Clinically patients undergoing gastrointestinal surgery are often
      accompanied with malnutrition, and these patients with liver dysfunction are easy
      to develop nutrient metabolic disorders. Therefore, improving the nutritional
      status of patients with liver dysfunction can improve the success rate of surgery
      and postoperative recovery. This article reviews the nutritional support in
      patients with liver dysfunction undergoing gastrointestinal surgery. 

PMID- 24277396
TI  - [Prognosis of patients with early enteral nutrition after gastrointestinal
      operation: a meta-analysis].
AB  - OBJECTIVE: To systematically assess the effect of early enteral nutrition support
      after gastrointestinal operation on prognosis. METHODS: The Cochrane Library,
      PubMed, CBM, CNKI, Wanfang, and VIP databases were retrieved via computer system
      for randomized controlled trails(RCTs) with early enteral nutrition support to
      patients undergoing gastrointestinal operation. Quality of studies was evaluated
      by the Cochrane Jadad rating scale. Nutrition indexes, bowel function indices,
      postoperative complications, health-economics indices were collected. Meta
      analysis was conducted with RevMan 5.2. RESULTS: Eleven relevant RCTs studies
      with 1087 cases were enrolled, including 541 patients in the study group(early
      enteral nutrition) and 546 in the control group. Meta-analysis showed that
      patients in the study group had significantly higher levels of plasma albumin and
      prealbumin than those in the control group(WMD=2.87, 95%CI:1.03-4.71; WMD=0.04,
      95%CI:0.02-0.05). The time of postoperative bowel ventilation in the study group
      was significantly shorter than that in the control group(WMD=4.10, 95%CI:-5.38-
      2.82). The postoperative complication rate in the study group was significantly
      lower as compared to the control group(RR=0.64, 95%CI:0.44-0.93). CONCLUSION:
      Early enteral nutrition support after gastrointestinal operation is safe and
      effective, which can improve the nutritional status, promote bowel function
      return, and reduce postoperative complication rate.

PMID- 24277397
TI  - [Clinical observation of early oral enteral nutrition after laparoscopic
      colectomy].
AB  - OBJECTIVE: To investigate the effect and safety of two types of early enteral
      nutrition, total protein(TP) and total protein with fibers(TPF-FOS), after
      laparoscopic colectomy. METHODS: Patients with colon cancer were divided into TP
      group and TPF-FOS group. Oral nutrition was given from the first postoperative
      day. Hemoglobin, albumin, prealbumin, white blood cell count, C-reactive protein,
      procalcitonin were tested before operation and on the first and seventh
      postoperative day. The time to first flatus, time to first bowel movement, fever,
      infection, and diarrhea were observed after operation. RESULTS: No significant
      difference was observed in hemoglobin, albumin, prealbumin, white blood cell
      count, C-reactive protein, and procalcitonin between these two groups. Higher
      proportion of patients defecated formed stool during the observation in TPF-FOS
      group(76.7% vs. 27.3%, P<0.01). Less abdominal bloating was found from the fourth
      to the seventh postoperative day in TPF-FOS group (5.8% vs. 15.2%, P<0.05).
      CONCLUSIONS: Both TP and TPF-FOS can be safely used for early oral enteral
      nutrition after laparoscopic colectomy. TPF-FOS may be more beneficial to the
      recovery of gastrointestinal function.

PMID- 24277398
TI  - [Safety and feasibility of early oral feeding after gastrectomy: a meta
      analysis].
AB  - OBJECTIVE: To systematically evaluate the safety and feasibility of early oral
      feeding after gastric cancer surgery. METHODS: Available literatures of Embase,
      PubMed, Journals@Ovid, Web of Science, Springerlink, Google Scholar, Wanfang, and
      CNKI published before October 2012 were searched. Inclusion criteria and quality
      assessment were performed. RESULTS: Nine studies including 778 patients
      undergoing gastrectomy were enrolled. Among them, 381 started oral intake before
      the recovery of bowel function(early oral feeding group), and 397 received
      traditional feeding. Differences in overall complication(RR=0.88, 95%CI:0.68
      1.16) and tolerance (RR=1.01, 95%CI:0.96-1.06) between the two groups were not
      statistically significant. Patients the in early oral feeding group had faster
      bowel function recovery (MD=-0.86, 95%CI:-1.20--0.51) and shorter hospital
      stay(MD=-2.40, 95%CI:-3.33--1.47). CONCLUSION: Early oral feeding after
      gastrectomy is safe and feasible, and associated with faster recovery of bowel
      function and earlier discharge from hospital.

PMID- 24277399
TI  - [Effect of postoperative early enteral nutrition on the recovery of humoral
      immune function in patients with colorectal carcinoma undergoing elective
      resection].
AB  - OBJECTIVE: To investigate the effect of postoperative early oral feeding on
      humoral immune function and clinical outcome in colorectal cancer patients.
      METHODS: Seventy patients with colorectal carcinoma requiring elective colorectal
      resection were prospectively enrolled and randomized into two groups: early oral
      feeding group(n=35) and conventional oral feeding group(n=35). The patients in
      early oral feeding group were started on oral feeding within 12 hours after
      operation, while patients in conventional group were started on oral feeding
      after the postoperative first passage of flatus. Postoperative parameters of
      clinic and humeral immune function were compared between two groups. RESULTS:
      Sixty-two patients eventually completed the study, including 32 cases in early
      oral feeding group and 30 cases in conventional oral feeding group. The average
      time to first passage of flatus[(2+/-1) d vs. (4+/-2) d, P<0.01], the first
      passage of stool [(3.8+/-1.6) d vs. (6.4+/-2.5) d, P<0.01], resumption of regular
      diet [(4+/-2) d vs. (8.2+/-2.2) d, P<0.01] and the postoperative hospital stay
      [(6+/-1) d vs. (11.7+/-3.8) d, P<0.01] were significantly shorter in early oral
      feeding group as compared to conventional oral feeding group. Significantly
      faster recovery of postoperative humoral immunity was found. Plasma levels of
      globulin [(24.1+/-2.4) g/L vs. (22.1+/-3.3) g/L, P<0.05], immunoglobulin
      G[(10.8+/-2.4) g/L vs. (8.7+/-2.1) g/L, P<0.01] and complement 4 [(0.24+/-0.09)
      g/L vs. (0.17+/-0.05) g/L, P<0.05] on postoperative day 3 were higher in early
      oral feeding group as compared to conventional oral feeding group. CONCLUSION:
      Application of postoperative early oral feeding in patients undergoing elective
      colorectal resection is safe and effective, which can lead to faster recovery of
      postoperative humoral immune function and bowel function, and shorter
      postoperative hospital stay.

PMID- 24277400
TI  - [Clinical observation of preoperative administration of enteral nutrition support
      in gastric cancer patients at risk of malnutrition].
AB  - OBJECTIVE: To evaluate safety and efficacy of preoperative administration of
      enteral nutrition support in gastric cancer patients at risk of malnutrition.
      METHODS: A single center randomized controlled clinical trial was performed in 60
      gastric cancer patients in West China Hospital from May to October 2012. Thirty
      patients were given enteral nutrition support(Ensure(R)) manufactured by Abbott
      Laboratories for ten consecutive days before surgical operation in the treatment
      group, and 30 patients were given an isocaloric and isonitrogenous homogenized
      diet in the control group for 10 days as well. The laboratory parameters of
      nutritional status and hepatorenal function were observed and compared between
      the two groups on admission, preoperative day 1 and postoperative day 3,
      respectively. Clinical observations, such as nausea and vomiting, were carried
      out until patients were discharged. RESULTS: Before the intervention, there were
      no significant differences in the baseline characteristics between the two
      groups. The levels of serum albumin [(33.9+/-5.6) g/L vs. (31.0+/-5.3) g/L,
      P<0.05], and hemoglobin[(103.4+/-7.7) g/L vs.(96.6+/-10.5) g/L, P<0.01] were
      significantly improved in the treatment group on postoperative day 3. However,
      the levels of body mass index, lymphocyte count, liver and renal function, serum
      glucose, sodium, and potassium were not significantly different between the two
      groups(all P>0.05). Moreover, two patients with nausea and one with vomiting in
      each group were found. In clinical observation period, no severe treatment
      related adverse event were observed. CONCLUSION: The enteral supplement with
      Ensure(R) in gastric cancer patients at risk of malnutrition during preoperative
      period is effective and safe, which is superior to homogenized diet and an
      appropriate choice for gastric cancer patients with nutritional risk.

PMID- 24277401
TI  - [Application of enteral nutrition in preoperative bowel preparation for rectal
      cancer patients undergoing radical operation].
AB  - OBJECTIVE: To explore the feasibility and safety of enteral nutrition in
      preoperative bowel preparation for rectal cancer patients undergoing radical
      operation. METHODS: Sixty rectal cancer patients undergoing selective low
      anterior resection were randomized into the trial group(n=30) and the control
      group(n=30). Patients in the trial group received clean liquid integral protein
      diet for 3 days before operation without mechanical bowel preparation. Patients
      in the control group received traditional diet and mechanical bowel preparation.
      The intraoperative and postoperative clinical data, the quality of bowel
      preparation, postoperative complications, and nutritional parameters were
      compared between the two groups. RESULTS: There were no significant differences
      in clinicopathological characteristics between the two groups before operation.
      The operative time, blood loss, quality of bowel preparation as well as
      postoperative hospital stay were not significantly different(all P>0.05). While
      the time to first flatus [(2.53+/-0.91) d vs. (3.03+/-0.68) d] and semi-liquid
      diet intake[(3.95+/-0.83) d vs. (4.52+/-1.14) d] were significantly shorter in
      the trial group as compared with the control group(all P<0.05). There were no
      death and no significant difference in postoperative complications [16.7%(5/30)
      vs. 20.0%(6/30), P>0.05]. The levels of postoperative total protein, albumin, and
      prealbumin decreased significantly. Meanwhile, the levels of postoperative
      albumin[(36.2+/-2.5) g/L vs. (33.5+/-2.6) g/L, P<0.01] and prealbumin [(325.4+/
      28.2) mg/L vs. (302.5+/-34.2) mg/L, P<0.01] in the trial group were significantly
      higher than those in the control group. CONCLUSIONS: Preoperative enteral
      nutrition can replace the mechanical bowel preparation with better efficacy, and
      improve the postoperative nutritional status without increasing surgical risk in
      rectal cancer patients undergoing radical operation.

PMID- 24277402
TI  - [Study on early postoperative nutritional support in elderly patients with
      gastric cancer].
AB  - OBJECTIVE: To explore the optimal postoperative nutritional support in elderly
      patients with gastric cancer. METHODS: One hundred and twenty elderly patients
      with gastric cancer undergoing radical gastrectomy were prospectively enrolled
      from January 2010 to March 2013 and randomly divided into total parenteral
      nutrition group(TPN, n=40), early total enteral nutrition group (TEN, n=40) and
      enteral plus parenteral nutrition group(EN+PN, n=40). Clinical charasteristics
      including treatment tolerance, nutritional indexes, immune indexes, time to first
      flatus, incidence of postoperative infection and anastomotic leakage, were
      analyzed and compared. RESULTS: Treatment tolerance in EN+PN group(97.5%, 39/40)
      was significantly higher than that in TPN group(82.5%, 33/40) and TEN
      group(80.0%, 32/40)(both P<0.05). The nutritional indices, including prealbumin,
      albumin, transferrin, body mass index, and the incidence of anastomotic leakage
      were similar in the 3 groups(P>0.05). The immune indices, including CD3, CD4,
      CD4/CD8, were significantly reduced after operation in each group. However, they
      were significantly higher in EN+PN group and TEN group than those in TPN
      group(both P<0.05). Furthermore, compared to the TPN group, the incidence of
      postoperative infection(surgical site infection, pulmonary infection, abdominal
      infection) was significantly lower and time to first flatus was significantly
      shorter in EN+PN group and TEN group. CONCLUSIONS: Early enteral nutrition after
      gastric cancer surgery is safe, simple and feasible. EN plus PN is the best way
      to administer postoperative nutritional support in elderly patients with gastric
      cancer.

PMID- 24277403
TI  - [Predictive value of three preoperative nutritional assessment methods in
      postoperative complications of gastrointestinal cancers].
AB  - OBJECTIVE: To compare the value of three preoperative nutritional assessment
      methods, European nutrition risk screening 2002(NRS 2002), mini-nutrition
      assessment(MNA) and subjective global assessment(SGA), in predicting
      postoperative complications of gastrointestinal cancer patients. METHODS: A total
      of 235 patients with gastrointestinal cancers, including 31 esophageal cancers,
      82 gastric cancers, and 122 colorectal cancers, in our hospital from January 2012
      to June 2013 were prospectively enrolled. Preoperative nutritional status was
      evaluated with above 3 methods respectively. Postoperative complication rates
      were compared among different preoperative nutritional status. RESULTS: According
      to SGA score, the morbidity of severe-moderate, mild and no malnourished patients
      was 40.5%(17/42), 25.3%(22/87) and 14.2%(15/106) respectively(P<0.01). According
      to MNA score, the morbidity of patients with malnutrition, at risk of
      malnutrition and without malnutrition was 32.9%(23/70), 24.7%(18/73) and
      14.1%(13/92) respectively(P<0.05). According to NRS 2002, the morbidity of
      patients at malnutrition risk and without malnutrition risk was 27.6%(27/98) and
      19.7%(27/137) respectively(P>0.05). Multiple regression analysis revealed that
      both SGA and MNA scores were predictive factors for the development of
      postoperative complications(both P<0.01). The sensitivity of SGA score for
      predicting complications was higher compared to MNA score (90.7% vs. 79.6%),
      while the specificity was similar(49.7% vs. 50.8%). CONCLUSIONS: Both SGA and MNA
      scores can effectively predict the development of postoperative complications in
      gastrointestinal cancer patients, and SGA score has better sensitivity. SGA score
      is recommended for decision-making regarding preoperative nutrition support.

PMID- 24277405
TI  - [Effect of chewing gum on the promotion of intestinal function recovery after
      colorectal surgery: a meta-analysis].
AB  - OBJECTIVE: To examine the safety and efficacy of chewing gum in promoting
      intestinal function recovery after colorectal surgery. METHODS: A thorough search
      of PubMed, Cochrane Library, CNKI, CBM and Wanfang data was performed. Randomized
      controlled trials(RCTs) about efficacy and safety of chewing gum in promoting
      intestinal function recovery after colorectal surgery were collected and meta
      analysis was carried out with RevMan 5.0 software. RESULTS: Thirteen RCTs
      including 993 patients were enrolled in this study with 499 patients in the
      chewing gum group and 494 patients in control group. Meta-analysis revealed that
      chewing gum could significantly reduce the time to first passage of flatus(MD=
      11.66 h, 95%CI:-17.26--6.07, P<0.05), the time to the first defecation (MD=-32.31
      h, 95%CI:-56.89--7.73, P<0.05), and postoperative hospital stay(MD=-1.10 d,
      95%CI:-1.93--0.27, P<0.05) after colorectal surgery. Patients in chewing gum
      group also experienced less discomfort from bowel distension(OR=0.52, 95%CI:0.35
      0.80, P<0.05) due to postoperative paralytic ileus. No significant difference in
      the incidence of nausea and vomiting was found. CONCLUSIONS: The addition of
      chewing gum, a well tolerated intervention, to standard treatment may facilitate
      intestinal recovery and contribute to a shorter hospital stay following
      colorectal surgery.

PMID- 24277404
TI  - [Comparison study of three methods of digestive tract reconstruction after
      radical gastrectomy in gastric cancer patients].
AB  - OBJECTIVE: To investigate the ideal digestive tract reconstruction methods among
      three different surgical methods after radical gastrectomy of gastric cancer
      patients. METHODS: A total of 123 patients who received elective radical
      gastrectomy for gastric cancer from February 2010 to August 2011 were
      prospectively enrolled and randomly divided into radical proximal gastrectomy and
      jejunal interposition group, radical proximal gastrectomy and esophageal with the
      posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y
      esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of
      reflux esophagitis were observed, gastric emptying tests were done, liver and
      kidney function was also monitored. The quality of life was documented before
      operation, and one and twelve months after operation. RESULTS: No significant
      differences were found among these three groups in the pH value of lower part of
      esophagus, the blood regular test results and the functional parameters of kidney
      and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis
      was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in
      esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux
      en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and
      8(19.5%) patients presented reflux of barium meal in these three groups,
      respectively (P=0.046). There were no statistically significant difference in PH
      at the distal esophagus(6.9+/-0.2 vs. 6.8+/-0.1 vs. 6.9+/-0.1, P=0.196). The
      quality of life was significantly improved one year after surgery in terms of
      general status, physical function, emotional function, fatigue, nausea/vomiting,
      pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition
      superior than the other two methods. CONCLUSION: Three methods of digestive tract
      reconstruction in radical gastrectomy of gastric cancer patients can improve the
      health status and the quality of life in gastric cancer patients. Radical
      proximal gastrectomy and jejunal interposition is the preferred method.

PMID- 24277406
TI  - [Clinical analysis of 29 cases with neuroendocrine neoplasm in the digestive
      system].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of neuroendocrine neoplasm
      (NEN) in the digestive system. METHODS: Clinical data of 29 patients with NEN
      from January 2000 to December 2012 in The First Affiliated Hospital of Dalian
      Medical University were analyzed retrospectively and the prognosis was evaluated
      according to the new WHO classification. RESULTS: There were 19 males and 10
      females and the average age was 46.5 years. All the patients had no clinical
      manifestations of carcinoid syndrome, and they all received surgical treatment.
      Two cases were gastric neuroendocrine carcinoma(NEC), who received radical total
      gastrectomy and distal gastric resection respectively. Three cases had neoplasm
      in the duodenum, including 2 NEC and 1 neuroendocrine tumor(NET), and they all
      underwent Whipple's procedure. Two cases were small intestine NEC, who received
      partial small intestine resection. Three cases had neoplasm in the appendix,
      including 1 NEC treated with right hemicolectomy and 2 NET with appendectomy. One
      case was ascending colon NEC, who received right hemicolectomy. Eighteen cases
      had neoplasm in the rectum, including 4 NEC treated with low anterior resection
      and abdominoperineal resection respectively, and 14 cases of NET underwent low
      anterior resection, local resection, and endoscopic resection respectively. The 1
      and 3- year survival rates of 13 NEC cases were 38.4% and 7.7% respectively. The
      5-year survival rate of 16 NET cases was 81.3%. CONCLUSIONS: NEN of digestive
      system is located mainly in the rectum and the clinical symptom is unspecific.
      Radical resection of NEN is the preferred treatment. The prognosis of NEC is
      poor, and that of NET is better.

PMID- 24277407
TI  - [Comparative study on the quality of life in patients with prevertebral or
      retrosternal reconstruction after cervical tubular gastroesophagostomy].
AB  - OBJECTIVE: To compare the quality of life in patients with prevertebral or
      retrosternal reconstruction after cervical tubular gastroesophagostomy. METHODS:
      A total of 167 patients enrolled in this prospective study from July 2008 to June
      2012 in Shantou Central Hospital, and divided into prevertebral route group(85
      cases) and retrosternal route group(82 cases) according to the random number
      table method. Quality of life questionnaire was investigated 1, 3, 6, 9, and 12
      months after operation respectively. RESULTS: The incidence of anastomotic
      stenosis was lower in the prevertebral route group (P<0.05). However, the
      differences in perioperative general conditions between the two groups were not
      statistically significant(all P>0.05). One hundred and forty-nine patients
      completed the postoperative quality of life questionnaire. Dysphagia and
      swallowing retching symptom were better, while acid reflux and heartburn symptom
      were more serious in prevertebral route group as compared to retrosternal route
      group(all P<0.05). Overall quality of life score difference between the two
      groups was not statistically significant(P>0.05). CONCLUSIONS: For digestive
      tract reconstruction after resection of esophageal cancer, tubular
      gastroesophagostomy by prevertebral or retrosternal route both can obtain better
      quality of life after surgery. Swallowing function after surgery of the former is
      superior to the latter, but the reflux symptoms is more serious. Therefore the
      two mehods have their own advantages and disadvantages, and the choice of route
      should be depended on clinical experience and patient condition.

PMID- 24277408
TI  - [Study on the application of laparoscopy-assisted radical gastrectomy for gastric
      cancer in the elderly].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopy-assisted D2
      radical gastrectomy for elderly patients with gastric cancer. METHODS: From
      October 2007 to October 2012, 233 gastric cancer patients over 65 years underwent
      D2 lymph node dissection. Among them, 109 patients underwent laparoscopy-assisted
      radical gastrectomy(LAG group), while 124 patients underwent conventional open
      gastrectomy(OG group). RESULTS: Compared to the OG group, LAG group was
      associated with less bleeding [(102.5+/-34.3) ml vs. (181.7+/-73.8) ml, P<0.05],
      quicker postoperative recovery of bowel function[(2.8+/-0.6) d vs. (4.0+/-1.2) d,
      P<0.05], shorter postoperative length of hospital stay[(10.7+/-7.5) d vs.(14.2+/
      6.5) d, P<0.05], longer operative time [(231.2+/-51.4) min vs. (208.5+/-53.6)
      min, P<0.05]. The postoperative complication rate of LAG group and OG group was
      10.1%(11/109) and 21.0%(26/124) respectively(P<0.05). Short-term quality of life
      of LAG group was better than that of OG group(P<0.05). The 5-year survival rates
      were 54.5% and 59.2% in LAG and OG groups respectively, and there was no
      significant difference(P>0.05). CONCLUSIONS: Efficacy of laparoscopy-assisted D2
      radical gastrectomy is similar to open gastrectomy in elderly gastric cancer
      patients with less invasiveness.

PMID- 24277409
TI  - [Regulation mechanism study of S100A6 on invasion and metastasis in gastric
      cancer].
AB  - OBJECTIVE: To detect the expression of S100A6 in gastric cancer, and to
      investigate the regulation mechanism of S100A6 in invasion and metastasis of
      gastric cancer. METHODS: Expression of S100A6 protein in gastric cancer
      specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue
      specimens was detected by immunohistochemical staining in 166 patients with
      gastric cancer from January 1995 to December 2001. Their association with
      clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was
      used to detect the downstream factors potentially regulated by S100A6 in gastric
      cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell
      line AGS, and cell invasion experiment and real time Q-polymerase chain
      reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA
      expression of invasion-related factors (CDK5 and FLJ12438) in transfection group,
      negative control group and blank control group, respectively. RESULTS: Low
      expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In
      gastric cancer, liver and lymph node metastasis tissues, S100A6 protein
      expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor
      cells of invasive edge. The expression rates of gastric cancer, liver and lymph
      node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30)
      respectively. The high expression of S100A6 was associated with tumor local
      invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM
      stages(all P<0.05). The transmembrane cell number was 31.3+/-5.5 in the S100A6
      transfection group, significantly higher than that in negative control group
      (7.7+/-1.5) and blank control group (9.3+/-2.1)(both P<0.05), indicating an
      increase of cell invasion after S100A6 transfection. In transfection group, CDK5
      mRNA expression was significantly higher than that in negative control group and
      blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the
      three groups(P<0.05). CONCLUSION: S100A6 may affect the malignant biological
      behavior of gastric cancer cells by regulating the expressions of down-stream
      invasion-associated factors, such as CDK5.

PMID- 24277410
TI  - [Expression of cancerous inhibitor of protein phosphatase 2A in tissue microarray
      of colorectal cancer and its clinical significance].
AB  - OBJECTIVE: To investigate the expression of cancerous inhibitor of protein
      phosphatase 2A(CIP2A) in human colorectal cancer, and to examine the association
      of CIP2A expression with clinicopathology and prognosis. METHODS: CIP2A
      expression in colorectal cancer tissue microarray of 92 cases was detected by
      immunohistochemistry method. RESULTS: Up-regulated CIP2A expression was closely
      related with TNM staging, histological type, peritoneal seeding and liver
      metastasis (all P<0.05), but not related with gender, age, tumor location, CEA,
      family history and grade of differentiation. Overall survival rates of 1-, 3-, 5
      , and 10-year in high CIP2A expression group were 97.1%, 71.4%, 59.2%, and 44.4%
      respectively, significantly lower than 98.2%, 85.7%, 80.3%, and 74.9% in low
      CIP2A expression group(P=0.021). Multivariate analysis showed that CIP2A was not
      an independent factor associated with prognosis(P=0.099, HR=1.982, 95%CI:0.879 to
      4.469). CONCLUSIONS: Up-regulated CIP2A expression is closely related to
      clinicopathology of colorectal cancer. CIP2A may be used as a potential
      predictive marker of metastasis, prognosis and therapeutic target in colorectal
      cancer.

PMID- 24277411
TI  - [Expression tumor stem cell surface marker CD44 in gastric cancer and its
      significance].
AB  - OBJECTIVE: To investigate the expression of tumor stem cell surface marker CD44
      in gastric cancer and its clinical value. METHODS: Expressions of CD44 protein
      family, including CD44s, CD44v5 and CD44v6, in gastric cancer and peritumoral
      tissues specimens were detected by immunohistochemistry in 156 patients with
      gastric cancer from December 2006 to December 2007. Associations of CD44 family
      expressions with of clinicopathological parameters and prognosis in gastric
      cancer patients were examined. RESULTS: The positive rates of CD44s expression in
      gastric cancer and peritumoral tissues were 50.0%(78/156) and 40.3%(63/156)
      respectively(P>0.05). The positive rates of CD44v5 and CD44v6 expression in
      gastric cancer were 49.3% and 63.4%, significantly higher than those in
      peritumoral tissues(7.6% and 0 respectively, all P<0.05). There were no positive
      correlations among the expression levels of CD44s, CD44v5 and CD44v6(all P>0.05).
      High expression rate of CD44s was associated with depth of invasion, lymph node
      metastasis and TNM stages. CD44v5 expression was only associated with depth of
      invasion. CD44v6 expression was associated with depth of invasion, lymph node
      metastasis, TNM stages and Lauren classification. The 5-year survival rates in
      the positive and negative groups of CD44s, CD44v5 and CD44v6 expressions were
      35.8% and 52.5%(P<0.05), 38.9% and 49.3%(P>0.05), 26.2% and 75.4%(P<0.05)
      respectively. Only the CD44v6 expression was an independent prognostic factor for
      gastric cancer(RR=1.931, 95%CI:1.183-3.152). CONCLUSION: CD44 plays an important
      role in invasion and lymph node metastasis, and may serve as potential predictors
      of prognosis in gastric cancer.

PMID- 24277412
TI  - [Pharmacological mechanisms and effects of amino acid nutrients].
AB  - Common amino acid nutrients mainly contain glutamine, arginine, leucine,
      methionine and cysteine, which are not only the components participating in body
      protein synthesis, but also regulate the patients' immune system and metabolism.
      Glutamine can improve the intestinal barrier, reduce inflammatory reaction, and
      promote immunity recovery, but the clinical effects of different patients with
      different diseases are still lack of clear conclusions. The catabolism of
      arginine can produce NO, promoting the inflammatory reaction, and can also
      generate ornithine, alleviating inflammatory reaction and promoting wound
      healing. Two competing ways coexist, but the specific effects on different
      diseases have no clear conclusions yet. Leucine promotes muscle protein synthesis
      mainly through mTOR pathway, however, the influence on metabolism is still
      debating. Sulfur-containing amino acids methionine and cysteine can promote the
      synthesis of connective tissue and collagen conducive to wound healing, and their
      beneficial effects on lipid metabolism are of value. The purpose of this review
      is to cover potential beneficial physiological mechanisms of amino acid
      nutrients, to describe their results of clinical applications and to evaluate the
      interactions among individual nutrients or between individual nutrients and body.

PMID- 24277413
TI  - [Progress of research in the relationship between microorganisms and colorectal
      cancer].
AB  - Colorectal cancer is a common carcinoma of gastrointestinal tract, and its
      incidence is associated with genetic mutations, environment as well as
      inflammation. Recent studies have shown that many microorganisms may have played
      an important role in pathogenesis of colorectal cancer. The common bacteria
      involved in colorectal cancer are Streptococcus bovis, Helicobacter pylori,
      Escherichia coli, Bacteroides, and Fusobacterium, etc. The common viruses are
      Polyomavirus, Epstein Barr virus, Cytomegalovirus and Human papillomavirus, etc.
      The detailed mechanism of these microorganisms in the pathogenesis of colorectal
      cancer is unclear, and there are no reports on specific pathogenic microorganisms
      which cause the disease directly. The direction of future researches will focus
      on metagenome, metatranscriptome, and metaproteome of microorganisms associated
      with the incidence of colorectal cancer. 

PMID- 24277414
TI  - Characterization of antagonistic-potential of two Bacillus strains and their
      biocontrol activity against Rhizoctonia solani in tomato.
AB  - To investigate the biocontrol mechanism of two antagonistic Bacillus strains
      (Bacillus subtilis MB14 and Bacillus amyloliquefaciens MB101), three in vitro
      antagonism assays were screened and the results were concluded that both strains
      inhibited Rhizoctonia solani growth in a similar manner by dual culture assay,
      but the maximum percent of inhibition only resulted with MB101 by volatile and
      diffusible metabolite assays. Moreover, cell free supernatant (CFS) of MB101 also
      showed significant (p > 0.05) growth inhibition as compared to MB14, when 10 and
      20% CFS mix with the growth medium of R. solani. After in vitro-validation, both
      strains were evaluated under greenhouse and the results concluded that strain
      MB101 had significant biocontrol potential as compared to MB14. Strain MB101 was
      enhanced the plant height, biomass and chlorophyll content of tomato plant
      through a higher degree of root colonization. In field trials, strain MB101
      showed higher lessening in root rot symptoms with significant fruit yield as
      compare to strain MB14 and infected control. Next to the field study, the
      presence of four antibiotic genes (srfAA, fenD, ituC, and bmyB) also concluded
      the antifungal nature of both Bacillus strains. Phylogenetic analysis of protein
      sequences revealed a close relatedness of three genes (srfAA, fenD, and ituC)
      with earlier reported sequences of B. subtilis and B. amyloliquefaciens. However,
      bmyB showed heterogeneity in among both strains (MB14 and MB101) and it may be
      concluded that higher degree of antagonism, root colonization and different
      antibiotic producing genes may play an important role in biocontrol mechanism of
      strain MB101. 

PMID- 24277415
TI  - Combined aberrant expression of microRNA-214 and UBC9 is an independent
      unfavorable prognostic factor for patients with gliomas.
AB  - MicroRNA-214 (miR-214) plays an important role in tumor cell proliferation,
      migration and invasion, as well as tumor angiogenesis. Ubiquitin-conjugating
      enzyme 9 (UBC9) is implicated in regulating several critical cancer-related
      pathways. Recent study has demonstrated that miR-214 reduction may facilitate
      UBC9 expression and may be involved in the regulation of glioma cell
      proliferation. The aim of this study was to clarify the clinical significance of
      miR-214 and UBC9 in human glioma, which has not been fully elucidated.
      Quantitative real-time polymerase chain reaction analysis was used to
      characterize the expression patterns of miR-214 and UBC9 mRNA in 108 glioma and
      20 normal brain tissues. The associations of miR-214 and UBC9 mRNA expressions
      with clinicopathological factors and prognosis of glioma patients were also
      statistically analyzed. Compared with normal brain tissues, the expression levels
      of miR-214 and UBC9 mRNA in glioma tissues were significantly downregulated and
      upregulated, respectively (both P < 0.001). There was a negative correlation
      between miR-214 and UBC9 mRNA expression in glioma tissues (r = -0.61, P = 0.01).
      Additionally, the combined miR-214 downregulation and UBC9 upregulation (miR-214
      low/UBC9-high) was significantly associated with advanced pathological grade (P =
      0.008). Moreover, Kaplan-Meier survival and Cox regression analyses showed that
      the glioma patients with miR-214-low/UBC9-high expression had poorest overall
      survival (P < 0.001) and conjoined expression of miR-214-low/UBC9-high was an
      independent prognostic indicator of glioma (P = 0.01). Furthermore, subgroup
      analyses showed that miR-214-low/UBC9-high expression was significantly
      associated with poor overall survival in glioma patients with high pathological
      grades (for grade III-IV: P < 0.001). This prospective study offers the
      convincing evidence for the first time that miR-214 and its target gene UBC9 may
      contribute to the development and the clinical outcome of glioma, and are
      valuable prognostic factors for glioma patients. A combined detection of miR
      214/UBC9 expression may benefit us in predicting the prognosis of patients with
      advanced gliomas.

PMID- 24277416
TI  - Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic
      cytokines in patients with multiple myeloma.
AB  - Many cytokines possess variable roles in the pathogenesis of multiple myeloma.
      Macrophage inflammatory protein-1alpha (MIP-1alpha) is an osteoclast-activating
      factor with a major role in myeloma bone disease. The aim of the study was to
      examine its participation in the angiogenic process of the disease. We measured,
      by enzyme-linked immunosorbent assays, its serum levels in 56 newly diagnosed
      myeloma patients, in several skeletal grades and stages of the disease and in 25
      healthy controls. Concurrently, we measured serum levels of the angiogenic
      cytokines basic-fibroblast growth factor, hepatocyte growth factor and
      interleukin-18. All the above cytokines were higher in myeloma patients (p <
      0.001 for all cases) and were increasing in parallel with disease stage (p <
      0.001 for all cases) and skeletal grade (p < 0.04 for MIP-1alpha and p < 0.001
      for the other cases). Moreover, positive correlations between MIP-1alpha and all
      the angiogenic cytokines were noted (p < 0.001 for all cases). MIP-1alpha seems
      to be a predominant factor responsible for the enhancement of bone resorption and
      increased angiogenesis. The positive correlation between MIP-1alpha and the
      angiogenic chemoattractants supports the involvement of these factors in the
      biology of myeloma cell growth. Moreover, they could be used as possible
      therapeutic targets as well as markers of disease activity.

PMID- 24277417
TI  - Tumor necrosis factor-related apoptosis inducing ligand gene polymorphisms are
      correlated with gastric cancer in central China.
AB  - PURPOSE: To investigate the association of tumor necrosis factor-related
      apoptosis inducing ligand (TRAIL) gene polymorphisms with gastric cancer in
      Chinese Han population in central China. METHODS: A total of 304 patients with
      gastric cancer confirmed by histopathology and 421 unrelated healthy controls
      were studied. Gene polymorphisms of TRAIL (G1525A and C1595T) were genotyped by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. RESULTS: The frequency of the genotype carriers of TRAIL 1525A (GA +
      AA) and 1595T (CT + TT) was significantly lower in gastric cancer than in healthy
      controls (37.2% vs. 61.5%, P < 0.001, OR = 0.581, 95% CI 0.442 ~ 0.764; 36.2% vs.
      62.0%, P < 0.001, OR = 0.570, 95% CI 0.433 ~ 0.750, respectively). Stratification
      analysis showed that both TRAIL 1525A (GA + AA) and 1595T (CT + TT) carriers were
      associated with poorly-differentiated gastric cancer compared to 1525GG genotype
      and 1595CC genotype (OR = 0.516, 95%CI 0.279 ~ 0.957, P = 0.026; OR = 0.395,
      95%CI 0.207 ~ 0.753, P = 0.004, respectively). CONCLUSIONS: TRAIL G1525A and
      C1595T gene polymorphisms were significantly correlated with the susceptibility
      to gastric cancer in Chinese Han population in central China.

PMID- 24277418
TI  - Older adolescents' thinking about academic/vocational and interpersonal
      commitments.
AB  - Sixty-eight college students listed the factors they consider or would consider
      when making the following commitments: choosing courses, choosing a major,
      choosing a career, choosing a friend, choosing a romantic partner, and choosing a
      lifelong partner. In addition, subjects provided their own definition
      ofcommitment in an unstructured essay. Subjects listed more factors, more
      distinct types of factors, and more original factors for interpersonal
      commitments than for academic/vocational commitments. There were few gender
      differences found in these measures, contradicting the idea that men and women
      think differently about different commitments. In addition, few gender or class
      year differences were found in the themes present in the essay
      definingcommitment. Conceptions of commitment, as described in essays, predicted
      thinking about specific commitments only slightly. 

PMID- 24277419
TI  - Student teachers' perceptions of the identity formation process.
AB  - Student teachers were asked to respond to profiles of various styles of dealing
      with adolescent identity issues. Student teachers responded most favorably to the
      profile indicating adolescent exploration of occupational and ideological
      alternatives (Moratorium) and least favorably to an apparent nonconcern with
      adolescent issues (Diffuse). Commitment to plans and beliefs with closedness to
      alternatives (Foreclosure) received intermediate evaluations. Consistent with
      Eriksonian notions, but at variance with empirical findings, the Moratorium style
      was rated highest in psychological health. Student teachers preferred the
      Moratorium-style individual as prospective students; the Diffuse-style one the
      least. Implications for teacher training and educational practice were examined,
      and areas of further research were outlined. 

PMID- 24277420
TI  - Gender differences associated with playing high school varsity soccer.
AB  - Despite the increased participation of girls in competitive high school
      athletics, it is unclear that play on sports teams holds the same meaning for
      adolescent boys and girls. This study investigated school, grade, (freshman and
      sophomore vs junior and senior), and gender differences associated with a range
      of factors related to participation in high school varsity soccer play among 65
      students attending two high schools, one emphasizing achievement, the other
      emphasizing competitive involvement in athletics, including soccer. Also of
      interest was the relationship between both soccer involvement and soccer
      knowledge and school climate, empathy, occupational interest, and perceived
      parent behavior. Because gender differences were found in comparative and
      correlational analysis, it is concluded that play on varsity soccer teams holds
      different meanings and values for adolescent boys and girls. 

PMID- 24277421
TI  - Different views: The impact of sex, area of residence, and victimization on
      teenagers' explanations for delinquency.
AB  - It was hypothesized, following attribution theory, thatpsychological closeness
      (such as familiarity, similarity, and physical proximity) to the perpetrators of
      delinquency would lead to its being explained in terms of external (environmental
      and situational) factors. In contrast, since being a victim of delinquent acts
      imbues one with personal relevance it should promote internal (dispositional and
      personal) explanations. Consistent with these hypotheses, the 15-year-olds in the
      present study endorsed less individualistic explanations and stressed the social
      functions of delinquency more than did older subjects in an earlier study (A.
      Furnham and M. Henderson [1983] "Lay Theories of Delinquency,"European Journal of
      Social Psychology, 13: 107-112). Moreover, males, those living closer to the city
      center, and nonvictims favored external explanations more than did females, those
      living on the outskirts of the city and in rural areas and victims. It is
      concluded that social explanations for delinquency are informed both by group
      membership and by the context and quality of experiences of delinquency. 

PMID- 24277428
TI  - Sericite in the remediation of Cd(II)- and Mn(II)-contaminated waters: batch and
      column studies.
AB  - Sericite, a mica-based natural clay was employed in the remediation of waters
      contaminated with two important heavy metal toxic ions, viz. Cd(II) and Mn(II),
      under batch and column experimentation. The batch reactor studies were intended
      to study various physicochemical parameters, viz. effect of sorptive pH,
      concentration, contact time, and background electrolyte concentrations which
      helped to deduce the mechanism involved at the solid/solution interface. The
      percent uptake of Cd(II) and Mn(II) was increased with increasing of the sorptive
      pH, and almost 100 % of these cations were removed at pH 10. Equilibrium-state
      sorption data was modeled and fitted well to the Langmuir and Freundlich
      adsorption isotherms. The kinetic data followed the pseudo-first-order and pseudo
      second-order kinetic models. Increasing the background electrolyte concentrations
      by 100 times caused significant decrease of the uptake of Cd(II) and Mn(II) ions,
      which inferred that these metal cations were less adsorbed specifically and
      predominantly attached with relatively weak electrostatic attraction onto the
      solid surface. Additionally, the fixed-bed column reactor operations were also
      performed to assess the suitability of sericite in the attenuation of Cd(II) and
      Mn(II) from aqueous solutions under dynamic conditions. The breakthrough data
      obtained were successfully utilized to fit into a nonlinear fitting of Thomas
      equation. The results showed that the naturally and abundantly available sericite
      could be a potential natural material in the remediation of aquatic environment
      contaminated with Cd(II) and Mn(II).

PMID- 24277429
TI  - Biostimulation as an attractive technique to reduce phenanthrene toxicity for
      meiofauna and bacteria in lagoon sediment.
AB  - A microcosm experiment was setup to examine (1) the effect of phenanthrene
      contamination on meiofauna and bacteria communities and (2) the effects of
      different bioremediation strategies on phenanthrene degradation and on the
      community structure of free-living marine nematodes. Sediments from Bizerte
      lagoon were contaminated with (100 mg kg(-1)) phenanthrene and effects were
      examined after 20 days. Biostimulation (addition of nitrogen and phosphorus
      fertilizer or mineral salt medium) and bioaugmentation (inoculation of a
      hydrocarbonoclastic bacterium) were used as bioremediation treatments. Bacterial
      biomass was estimated using flow cytometry. Meiofauna was counted and identified
      at the higher taxon level using a stereomicroscope. Nematodes, comprising
      approximately two thirds of total meiofauna abundance, were identified to genus
      or species. Phenanthrene contamination had a severe impact on bacteria and
      meiofauna abundances with a strong decrease of nematodes with a complete
      disappearance of polychaetes and copepods. Bioremediation counter balanced the
      toxic effects of phenanthrene since meiofauna and bacteria abundances were
      significantly higher (p < 0.01) than those observed in phenanthrene
      contamination. Up to 98 % of phenanthrene removal was observed. In response to
      phenanthrene contamination, the nematode species had different behavior:
      Daptonema fallax was eliminated in contaminated microcosms, suggesting that it is
      an intolerant species to phenanthrene; Neochromadora peocilosoma, Spirinia
      parasitifera, and Odontophora n. sp., which significantly (p < 0.05) increased in
      contaminated microcosms, could be considered as "opportunistic" species to
      phenanthrene whereas Anticoma acuminata and Calomicrolaimus honestus increased in
      the treatment combining biostimulation and bioaugmentation. Phenanthrene had a
      significant effect on meiofaunal and bacterial abundances (p < 0.05), with a
      strong reduction of density and change in the nematode communities.
      Biostimulation using mineral salt medium strongly enhanced phenanthrene removal,
      leading to a decrease of its toxicity. This finding opens exciting axes for the
      future use of biostimulation to reduce toxic effects of PAHs for meiofauna and
      bacteria in lagoon sediment.

PMID- 24277430
TI  - Biochar production increases the polycyclic aromatic hydrocarbon content in
      surrounding soils and potential cancer risk.
AB  - The objectives of the study were the identification of the source of
      contamination of soils and estimation of the potential cancer risk that may be
      caused by contact with soils situated in the vicinity of biochar production
      sites. Samples of soils collected in the immediate vicinity of traditional
      biochar-producing plants, located within the area of the Bieszczady National Park
      (Poland), were analysed for the content of polycyclic aromatic hydrocarbons
      (PAHs). The sum of the content of 16 PAHs varied within the range of 1.80-101.3
      MUg/g, exceeding the norms permitted in many European countries. The calculated
      coefficients on the basis of which one can determine the origin of PAHs
      (molecular diagnostic ratios) demonstrated that the potential source of PAHs in
      the soils may be processes related with the production of biochar. Estimation on
      the basis of the results of incremental lifetime cancer risks (ILCRs) within the
      range of 2.33 . 10(-4)-1.05 . 10(-1) indicated that the soils studied may
      constitute a significant cancer risk for persons who have contact with them. The
      values of ILCRS should be considered as at least high, which permits the
      conclusion that sites of that type may create a hazard to human health.

PMID- 24277431
TI  - Biomonitoring air quality during and after a public transportation strike in the
      center of Uberlandia, Minas Gerais, Brazil by Tradescantia micronucleus bioassay.
AB  - The aim of this study was to address the lack of information concerning the air
      quality in the city of Uberlandia, Minas Gerais, Brazil. In this study, we
      conducted an unprecedented experiment involving the in situ biomonitoring of air
      genotoxicity in the city center during and after a public transportation strike
      using the Tradescantia micronucleus test. The frequency of micronuclei was
      significantly higher in the city center compared with the reference site (Mann
      Whitney test, p < 0.05), with the highest MN levels being observed during public
      transport stoppage (Kruskal-Wallis, Dunn p < 0.01). In addition, the multiple
      linear regression analyses revealed that the low circulation of buses during
      public transport stoppage and the increase in the concentration of particulate
      matter from the increased flow of vehicles in the city center during the strike
      positively influenced the MN frequency. The climatic factors did not change
      during the biomonitoring period, reflecting the fact that climatic factors did
      not influence the MN frequency.

PMID- 24277432
TI  - Elucidation of the upper pathway of alicyclic musk Romandolide degradation in
      OECD screening tests with activated sludge.
AB  - The degradation of Romandolide ([1-(3',3'-dimethyl-1'-cyclohexyl)ethoxycarbonyl]
      methyl propanoate), a synthetic alicyclic musk, by activated sludge inocula was
      investigated using both the manometric respirometry test OECD 301F and the CO2
      evolution test. In addition to measuring its biodegradability, key steps of the
      upper part of the metabolic pathway responsible for Romandolide degradation were
      identified using extracts at different time points of incubation. Early
      metabolism of Romandolide yielded ester hydrolysis products, including Cyclademol
      (1-(3,3-dimethylcyclohexyl)ethanol). The principal metabolites after 31 days were
      identified as 3,3-dimethyl cyclohexanone and 3,3-dimethyl cyclohexyl acetate.
      Formation of 3,3-dimethyl cyclohexanone from Cyclademol by sludge was confirmed
      in subsequent experiments using Cyclademol as a substrate, indicating the
      involvement of an oxygen insertion reminiscent of a Baeyer-Villiger oxidation.
      Further mineralization of 3,3-dimethyl cyclohexanone was also confirmed in
      subsequent studies. Three steps were thus required for complete biodegradation of
      the alicyclic musk: (1) successive ester hydrolyses leading to the formation of
      Cyclademol with concomitant degradation of the resulting acids, (2) conversion of
      Cyclademol into 3,3-dimethyl cyclohexanone, and (3) further mineralization via
      ring cleavage.

PMID- 24277433
TI  - Day-night differences and seasonal variations of chemical species in PM10 over
      Xi'an, northwest China.
AB  - To investigate day-night differences and seasonal variations of PM10 and its
      chemical composition in an urban environment in Xi'an, northwest China, day- and
      nighttime PM10 mass and its chemical components including water-soluble ions
      (Na(+), NH4 (+), K(+), Mg(2+), Ca(2+), F(-), Cl(-), NO3 (-), and SO4 (2-)),
      organic carbon (OC), elemental carbon, and water-soluble organic carbon (WSOC)
      were measured on selected representative days from 20 December 2006 to 12
      November 2007. Annual mean PM10 concentration in this city was five times of the
      China Ambient Air Quality Standard for annual average (70 MUg m(-3)).
      Carbonaceous fractions and water-soluble ions accounted for nearly one third and
      12.4 %, respectively, of the annual mean PM10 mass. No dramatic day-night
      differences were found in the loadings of PM10 or its chemical components. Spring
      samples were highlighted by abundance of Ca(2+), while the secondary aerosol
      species (SO4 (2-), NO3 (-), and NH4 (+)) and OC dominated in summer, autumn, and
      winter samples. Relatively low NO3 (-)/SO4 (2-) ratio suggested that stationary
      source emissions were more important than vehicle emissions in the source areas
      in this city. Strong relationships between WSOC and biomass markers (water
      soluble K(+), OC1, and OP) were observed in winter and autumn, indicating that
      WSOC was derived mainly from biomass burning in these seasons. This was also
      supported by analysis results on the biomass burning events. In contrast, poor
      correlations between WSOC and biomass markers were demonstrated in summer and
      spring, implying that WSOC was mainly formed as secondary organic carbon through
      photochemical activities.

PMID- 24277434
TI  - Risk assessment of heavy metals and their source distribution in waters of a
      contaminated industrial site.
AB  - Industrially contaminated sites with hazardous materials are a priority and
      urgent problem all over the world. Appropriate risk assessment is required to
      determine health risks associated with contaminated sites. The present study was
      conducted to investigate distribution of potentially hazardous, heavy metal (As,
      Cd, Cr, Cu, Ni, Pb and Zn) concentrations in surface and groundwater samples
      collected during summer (pre-monsoon) and winter (post-monsoon) seasons from an
      industrially contaminated site, Hyderabad, India, with potential source of metal
      contamination because of industrial effluents and usage of pesticides in
      agriculture. Heavy metal (HM) concentrations were analysed by using inductively
      coupled plasma-mass spectrometer and were compared with permissible limits set by
      the World Health Organisation. Data obtained was treated using multivariate
      statistical approaches like R-mode factor analysis (FA), principal component
      analysis, cluster analysis, geoaccumulation index, enrichment factor,
      contamination factor and the degree of contamination. Health risk assessment like
      chronic daily intake (CDI) and hazard quotient (HQ) were also calculated.
      Relatively high levels were noted in surface water with average concentrations
      during summer and winter seasons showing 16.13 and 11.83 for As, 7.91 and 1.64
      for Cd, 88.33 and 32.90 for Cr, 58.11 and 28.26 for Cu, 53.62 and 69.96 for Ni,
      173.8 and 118.6 for Pb, and 2,943 and 1,889 MUg/L for Zn. While in groundwater,
      the mean metal levels during two seasons were 18.18 and 3.76 for As, 1.67 and
      0.40 for Cd, 29.40 and 5.15 for Cr, 17.03 and 4.19 for Cu, 25.4 and 6.09 for Ni,
      81.7 and 2.87 for Pb and 953 and 989 MUg/L for Zn, respectively. FA identified
      two factors with cumulative loadings of F1-60.82 % and F2-76.55 % for pre-monsoon
      surface water and F1-48.75 % and F2-67.55 % for groundwater. Whereas, three
      factors with cumulative loadings of F1-39.13 %, F2-66.60 % and F3-81.01 % for
      post-monsoon surface water and F1-50.31 %, F2-66.18 % and F3-81.54 % for
      groundwater. The health risk assessment like CDI and HQ indices with increased
      levels of hazardous elements in the surface and groundwater were safe for
      drinking purposes provided some water treatment methodologies are adopted.

PMID- 24277435
TI  - Source apportion of atmospheric particulate matter: a joint Eulerian/Lagrangian
      approach.
AB  - PM2.5 samples were collected during an annual monitoring campaign (January 2012
      January 2013) in the urban area of Naples, one of the major cities in Southern
      Italy. Samples were collected by means of a standard gravimetric sampler (Tecora
      Echo model) and characterized from a chemical point of view by ion
      chromatography. As a result, 143 samples together with their ionic composition
      have been collected. We extend traditional source apportionment techniques,
      usually based on multivariate factor analysis, interpreting the chemical analysis
      results within a Lagrangian framework. The Hybrid Single-Particle Lagrangian
      Integrated Trajectory Model (HYSPLIT) model was used, providing linkages to the
      source regions in the upwind areas. Results were analyzed in order to quantify
      the relative weight of different source types/areas. Model results suggested that
      PM concentrations are strongly affected not only by local emissions but also by
      transboundary emissions, especially from the Eastern and Northern European
      countries and African Saharan dust episodes. 

PMID- 24277436
TI  - Mitochondrial dysfunction in rabies virus infection of neurons.
AB  - Infection with the challenge virus standard-11 (CVS) strain of fixed rabies virus
      induces neuronal process degeneration in adult mice after hindlimb footpad
      inoculation. CVS-induced axonal swellings of primary rodent dorsal root ganglion
      neurons are associated with 4-hydroxy-2-nonenal protein adduct staining,
      indicating a critical role of oxidative stress. Mitochondrial dysfunction is the
      major cause of oxidative stress. We hypothesized that CVS infection induces
      mitochondrial dysfunction leading to oxidative stress. We investigated the
      effects of CVS infection on several mitochondrial parameters in different cell
      types. CVS infection significantly increased maximal uncoupled respiration and
      complex IV respiration and complex I and complex IV activities, but did not
      affect complex II-III or citrate synthase activities. Increases in complex I
      activity, but not complex IV activity, correlated with susceptibility of the
      cells to CVS infection. CVS infection maintained coupled respiration and rate of
      proton leak, indicating a tight mitochondrial coupling. Possibly as a result of
      enhanced complex activity and efficient coupling, a high mitochondrial membrane
      potential was generated. CVS infection reduced the intracellular ATP level and
      altered the cellular redox state as indicated by a high NADH/NAD+ ratio. The
      basal production of reactive oxygen species (ROS) was not affected in CVS
      infected neurons. However, a higher rate of ROS generation occurred in CVS
      infected neurons in the presence of mitochondrial substrates and inhibitors. We
      conclude that CVS infection induces mitochondrial dysfunction leading to ROS
      overgeneration and oxidative stress.

PMID- 24277437
TI  - Neurocognitive impairment in HIV-1 clade C- versus B-infected individuals in
      Southern Brazil.
AB  - HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared
      with clade B. This might influence neuropathogenesis by altering trafficking of
      monocytes into the CNS. A previous study suggested low rates of HIV-associated
      dementia in clade C-infected individuals. The present study evaluated
      neurocognitive impairment rates in clade B- and C-infected individuals from the
      same local population. HIV+ and HIV- participants were recruited from the same
      geographic region in Southern Brazil. We evaluated neuropsychological (NP)
      impairment using a screening instrument (the International HIV Dementia Scale
      (IHDS)), as well as a Brazilian Portuguese adaptation of a comprehensive battery
      that has demonstrated sensitivity to HIV-associated neurocognitive disorders
      (HAND) internationally. NP performance in controls was used to generate T scores
      and impairment ratings by the global deficit score (GDS) method. Clade
      assignments were ascertained by sequencing pol and env. Blood and cerebrospinal
      fluid were collected from all HIV+ participants. HIV+ and HIV- participants were
      comparable on demographic characteristics. HIV+ participants overall were more
      likely to be impaired than HIV- by the IHDS and the GDS. Clade B- and C-infected
      individuals were demographically similar and did not differ significantly in
      rates of impairment. The prevalence of pleocytosis, a marker of intrathecal
      cellular chemotaxis, also did not differ between clade B and C infections. Clade
      B and C HIV-infected individuals from the same geographic region, when
      ascertained using comparable methods, did not differ in their rates of
      neurocognitive impairment, and there was no evidence of differences in CNS
      chemotaxis.

PMID- 24277438
TI  - CD8 T lymphocytes encephalitis mimicking brain tumor in HIV-1 infection.

PMID- 24277441
TI  - Primary prevention and the family: Part I.

PMID- 24277440
TI  - Genotyping of human parechoviruses in Iranian young children with aseptic
      meningitis and sepsis-like illness.
AB  - Human parechoviruses (HPeV) are classified into 14 genotypes. HPeV1 and HPeV2 are
      the most prevalent genotypes in young children, which have been associated with
      mild to severe diseases. This study was conducted to investigate the involvement
      of HPeVs in aseptic meningitis and sepsis-like illness in Iran. Viral RNA was
      extracted from 148 cerebrospinal fluid samples from children <8 years old with
      primary diagnosis of aseptic meningitis and/or sepsis-like illness. Specific
      HPeV, HEV real-time PCR and HPeV typing were done to identify the infection rate
      of these viruses. HPeV and HEV were detected in 64 (43.24 %), 31 (20.94 %) of 148
      patients with 10 (6.75 %) coinfection. VP1/VP3 junction region was successfully
      sequenced from 12 of the HPeV-positive specimens, and all of them were identified
      as HPeV1. HPeV was more prevalent than HEV in both aseptic meningitis and sepsis
      like illness, so further studies are needed to understand the disease burden of
      HPeV infections, and clinical manifestations especially in specific illnesses of
      possible viral etiology. Direct detection of these viruses leads to reduce
      hospitalization and use of antibiotic, which are often followed by other
      complications in neonates and young children.

PMID- 24277439
TI  - Real-world impact of neurocognitive deficits in acute and early HIV infection.
AB  - The acute and early period of HIV-1 infection (AEH) is characterized by
      neuroinflammatory and immunopathogenic processes that can alter the integrity of
      neural systems and neurocognitive functions. However, the extent to which central
      nervous system changes in AEH confer increased risk of real-world functioning
      (RWF) problems is not known. In the present study, 34 individuals with AEH and 39
      seronegative comparison participants completed standardized neuromedical,
      psychiatric, and neurocognitive research evaluations, alongside a comprehensive
      assessment of RWF that included cognitive symptoms in daily life, basic and
      instrumental activities of daily living, clinician-rated global functioning, and
      employment. Results showed that AEH was associated with a significantly increased
      risk of dependence in RWF, which was particularly elevated among AEH persons with
      global neurocognitive impairment (NCI). Among those with AEH, NCI (i.e., deficits
      in learning and information processing speed), mood disorders (i.e., Bipolar
      Disorder), and substance dependence (e.g., methamphetamine dependence) were all
      independently predictive of RWF dependence. Findings suggest that
      neurocognitively impaired individuals with AEH are at notably elevated risk of
      clinically significant challenges in normal daily functioning. Screening for
      neurocognitive, mood, and substance use disorders in AEH may facilitate
      identification of individuals at high risk of functional dependence who may
      benefit from psychological and medical strategies to manage their
      neuropsychiatric conditions.

PMID- 24277442
TI  - Primary prevention of adolescent pregnancy: Promoting family involvement through
      a school curriculum.
AB  - In prevention work, practices are suggested by theories. Thus, the idea that
      family-centered prevention is beneficial already embodies a theoretical
      perspective about why certain approaches to prevention are more appropriate than
      others. Logic and research evidence both suggest that the family is an
      indispensable resource in the primary prevention of destructive sexual decisions
      by adolescents. This paper describes how one project draws upon the family to
      accomplish primary prevention. An Alternative National Curriculum (AANC) is
      currently being disseminated in selected public schools in three states, while
      promoting parent-teen involvement. This project is sponsored by the Office of
      Adolescent Pregnancy Programs (OAPP), Department of Health and Human Services,
      which has a legislative mandate under Title XX of the Public Health Service Act
      to sponsor family-centered demonstration projects that help prevent premarital
      teen sexual relations and pregnancy. A specific theoretical view of human nature,
      family life, and societal well-being has been drawn upon to produce AANC. It
      focuses on ethical and responsible behavior, the importance of family linkages,
      and how quality family living across generations can be achieved. 

PMID- 24277443
TI  - Promoting healthy emotional development in children.
AB  - This paper considers the fact that the literature on childrearing has
      traditionally not dealt with children's emotional processes. Developmental
      research has moved from a focus on permissive vs. authoritarian parenting
      attitudes toward a concern with promoting competence and coping skills in
      children; the prevention literature on effective parenting has been from a
      behavioral management or communication skills perspective. The argument is
      presented here that children's emotional expressiveness is a natural coping
      mechanism which serves a positive function in the prevention of psychopathology
      and the promotion of mental health, and that mental health professionals need to
      begin incorporating this information both into the primary prevention literature
      and training programs in effective parenting. 

PMID- 24277444
TI  - The need for and effectiveness of surrogate role models among single-parent
      children.
AB  - Divorce typically causes children to lose time with their fathers. Big Brother
      Big Sister agencies have been established to provide same-sex adult companions
      for children in single-parent homes and are thought to be an effective primary
      prevention agency by providing natural caregiving. A needs assessment made in one
      city indicated that a majority of single-parent children desired an adult
      (nonparent) companion, regardless of child's age or amount of social activity. A
      program evaluation of a Big Brother-Big Sister agency, completed several years
      after the needs assessment, revealed that parentsand agency volunteers perceived
      positive changes in the children as a result of program involvement. 

PMID- 24277445
TI  - Mass media and prevention: Guidelines for family life professionals.
AB  - The potential preventive impact of mass media on family life is tremendous. Yet,
      many social scientists are reluctant to become involved in mass media
      programming, and those who do often have few guidelines, standards, or training
      to help them utilize mass media. Categories of problems discussed include: a)
      communicating with and understanding media professionals; b) establishing and
      maintaining professional standards; c) dealing with an unsophisticated public
      obsessed with facts; and d) recognizing and programming for the characteristics
      of mass media audiences. Recommendations for social scientists are presented for
      each category. 

PMID- 24277446
TI  - Building cultural Bridges: U.S. Health Programs for indochinese refugees.

PMID- 24277447
TI  - Facets of the Tetsuo Nozoe legacy immortalized in an enduring series of
      International Symposia on Novel Aromatic Compounds (ISNA).

PMID- 24277448
TI  - [Myeloperoxidase in the neurodegenerative process of Parkinson's disease].
AB  - Myeloperoxidase (MPO) is a hemoprotein which is involved in the unspecific immune
      response. In this process hypochloric acid is released. Hypochloric acid can
      react with lipids and proteins and thus lead to cell damage. We were able to show
      that MPO, as well as a biomarker for MPO - 3-Chlorotyrosine - are upregulated in
      the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model of Parkinson's
      disease as well as in the disease itself. Ablation of MPO resulted in a
      neuroprotective effect in the MPTP-model. Herein we describe the different
      function of MPO, and how these can lead to the cellular demise as seen in
      Parkinson's disease. 

PMID- 24277450
TI  - Importance of 5alpha-reductase gene polymorphisms on circulating and
      intraprostatic androgens in prostate cancer.
AB  - PURPOSE: Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen
      biosynthetic 5alpha-reductase enzymes have been associated with an altered risk
      of biochemical recurrence after radical prostatectomy in localized prostate
      cancer. EXPERIMENTAL DESIGN: To gain potential insights into SRD5A biologic
      effects, we examined the relationship between SRD5A prognostic markers and
      endogenous sex-steroid levels measured by mass spectrometry in plasma samples and
      corresponding prostatic tissues of patients with prostate cancer. RESULTS: We
      report that five of the seven SRD5A markers differentially affect sex-steroid
      profiles of dihydrotestosterone and its metabolites in both the circulation and
      prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in
      intraprostatic testosterone levels was observed in the presence of the high-risk
      SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated
      predominantly with circulating levels of inactive glucuronides. Indeed, the
      rs12470143 SRD5A2 protective allele was associated with high circulating
      androstane-3alpha, 17beta-diol-17-glucuronide (3alpha-diol-17G) levels as opposed
      to lower levels of both 3alpha-diol-17G and androsterone-glucuronide observed
      with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349
      (V89L) risk variants, in strong linkage disequilibrium, were associated with
      higher circulating levels of 3alpha-diol-3G. The SRD5A2 rs676033 variant further
      correlated with enhanced intraprostatic exposure to 5alpha-reduced steroids
      (dihydrotestosterone and its metabolite 3beta-diol). Similarly, the SRD5A1
      rs166050C risk variant was associated with greater prostatic exposure to
      androsterone, whereas no association was noted with circulating steroids.
      CONCLUSIONS: Our data support the association of 5alpha-reductase germline
      polymorphisms with the hormonal milieu in patients with prostate cancer. Further
      studies are needed to evaluate if these variants influence 5alpha-reductase
      inhibitor efficacy.

PMID- 24277449
TI  - Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell
      lung cancer.
AB  - PURPOSE: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is
      undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via
      lactate transport modulation, to kill tumor cells reliant on glycolysis. We
      investigated the therapeutic potential of AZD3965 in small cell lung cancer
      (SCLC) seeking rationale for clinical testing in this disease and putative
      predictive biomarkers for trial use. EXPERIMENTAL DESIGN: AZD3965 sensitivity was
      determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor
      xenograft model. Proof of mechanism was sought via changes in intracellular/tumor
      lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western
      blot analysis. Drug resistance was investigated via MCT4 siRNAi and
      overexpression. The expression and clinical significance of MCT1 and MCT4 were
      explored in a tissue microarray (TMA) from 78 patients with SCLC. RESULTS:
      AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in
      hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced
      tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression
      was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX
      expression in the absence of MCT4 was observed in 21% of SCLC tumors.
      CONCLUSIONS: This study provides a rationale to test AZD3965 in patients with
      SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking
      in MCT4 are most likely to respond.

PMID- 24277452
TI  - Overexpression of the circadian clock gene Bmal1 increases sensitivity to
      oxaliplatin in colorectal cancer.
AB  - PURPOSE: The circadian clock gene Bmal1 is involved in cancer cell proliferation
      and DNA damage sensitivity. The aim of this study was to explore the effect of
      Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in
      colorectal cancer. EXPERIMENTAL DESIGN: Three colorectal cancer cell lines,
      HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal
      cancer cell proliferation was tested in vitro and in vivo. MTT and colony
      formation assays were performed to determine the sensitivity of colorectal cancer
      cells to oxaliplatin. Flow cytometry was used to examine changes in the cell
      cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1
      upon its overexpression were determined by Western blotting. Immunohistochemistry
      was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from
      patients treated with oxaliplatin-based regimens. RESULTS: Bmal1 overexpression
      inhibited colorectal cancer cell proliferation and increased colorectal cancer
      sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells
      model in vivo. Furthermore, the overall survival of patients with colorectal
      cancer with high Bmal1 levels in their primary tumors was significantly longer
      than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The
      progression-free survival of patients with high Bmal1 expression was also
      significantly longer than that of patients with low Bmal1 expression (11 vs. 5
      months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its
      ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION: Bmal1
      shows the potential as a novel prognostic biomarker and may represent a new
      therapeutic target in colorectal cancer.

PMID- 24277451
TI  - Cladribine with immediate rituximab for the treatment of patients with variant
      hairy cell leukemia.
AB  - PURPOSE: In contrast with the classic form, variant hairy cell leukemia (HCLv)
      responds poorly to single-agent purine analogs, expresses unmutated BRAF, has
      shorter overall survival, and lacks effective standard therapy. No treatment has
      achieved a high complete remission (CR) rate even in small series, and of 39
      reported cases from six studies, overall response rate after cladribine was 44%
      with 8% CRs. Rituximab has been found to increase the sensitivity of malignant
      cells to cladribine, suggesting that combination with cladribine might improve
      response in HCLv. To test this hypothesis, patients with HCLv were treated with
      simultaneous cladribine and rituximab. EXPERIMENTAL DESIGN: Patients with HCLv
      with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1
      to 5, with eight weekly doses of rituximab 375 mg/m(2) beginning day 1. Restaging
      was performed, and minimal residual disease (MRD) in blood and marrow was
      quantified using PCR, immunohistochemistry, and flow cytometry. RESULTS: By 6
      months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported
      cases treated with cladribine alone (P < 0.0001). Of the 9 CRs, 8 remain free of
      MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were
      observed when beginning cladribine and rituximab on the same day, although most
      patients required short-term steroids to prevent and treat rituximab infusion
      reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major
      infections. CONCLUSION: Although cladribine alone lacks effectiveness for early
      or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD
      and is feasible to administer.

PMID- 24277453
TI  - Interleukin-30 expression in prostate cancer and its draining lymph nodes
      correlates with advanced grade and stage.
AB  - PURPOSE: The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has
      been recognized as a novel immunoregulatory mediator endowed with its own
      functions. These are currently the subject of discussion in immunology, but
      completely unexplored in cancer biology. We set out to investigate the role of IL
      30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa)
      cells. EXPERIMENTAL DESIGN: IL-30 expression, as visualized by
      immunohistochemistry and real-time reverse transcriptase PCR on prostate and
      draining lymph nodes from 125 patients with prostate cancer, was correlated with
      clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of
      selected gene clusters was tested by flow cytometry and PCR array. RESULTS: IL
      30, absent in normal prostatic epithelia, was expressed by cancerous epithelia
      with Gleason >= 7% of 21.3% of prostate cancer stage I to III and 40.9% of
      prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T
      ILK) was higher in stage IV that in stage I to III prostate cancer (P = 0.0006)
      or in control tissue (P = 0.0011). IL-30 expression in prostate draining lymph
      nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P =
      0.0031) or in control nodes (P = 0.0023). The main IL-30 sources were identified
      as CD68(+) macrophages, CD33(+)/CD11b(+) myeloid cells, and CD14(+) monocytes. In
      vitro, IL-30 stimulated proliferation of hPCa cells and also downregulated
      CCL16/LEC, TNFSF14/LIGHT, chemokine-like factor (CKLF), and particularly CKLF
      like MARVEL transmembrane domain containing 3 (CMTM3) and greatly upregulated
      ChemR23/CMKLR. CONCLUSIONS: We provide the first evidence that IL-30 is
      implicated in prostate cancer progression because (i) its expression by prostate
      cancer or T- and LN-ILK correlates with advanced disease grade and stage; and
      (ii) IL-30 exerts protumor activity in hPCa cells.

PMID- 24277454
TI  - Telomere content and risk of second malignant neoplasm in survivors of childhood
      cancer: a report from the Childhood Cancer Survivor Study.
AB  - PURPOSE: Shorter constitutional telomere length has been associated with
      increased cancer incidence. Furthermore, telomere shortening is observed in
      response to intensive chemotherapy and/or ionizing radiation exposure. We aimed
      to determine whether less telomere content was associated with treatment-related
      second malignant neoplasms (SMN) in childhood cancer survivors. EXPERIMENTAL
      DESIGN: Using a nested case-control design, 147 cancer survivors with breast
      cancer, thyroid cancer, or sarcoma developing after treatment for childhood
      cancer (cases) were matched (1:1) with childhood cancer survivors without a SMN
      (controls). Cases and controls were matched by primary cancer diagnosis, years
      since diagnosis, age at the time of sample collection, years of follow-up from
      childhood cancer diagnosis, exposure to specific chemotherapy agents, and to
      specific radiation fields. We performed conditional logistic regression using
      telomere content as a continuous variable to estimate ORs with corresponding 95%
      confidence intervals (CI) for development of SMN. ORs were also estimated for
      specific SMN types, i.e., breast cancer, thyroid cancer, and sarcoma. RESULTS:
      There was an inverse relationship between telomere content and SMN, with an
      adjusted OR of 0.3 per unit change in telomere length to single-copy gene ratio
      (95% CI, 0.09-1.02; P = 0.05). Patients with thyroid cancer SMN were less likely
      to have more telomere content (OR, 0.04; 95% CI, 0.00-0.55; P = 0.01), but
      statistically significant associations could not be demonstrated for breast
      cancer or sarcoma. CONCLUSIONS: A relation between less telomere content and
      treatment-related thyroid cancer was observed, suggesting that shorter telomeres
      may contribute to certain SMNs in childhood cancer survivors.

PMID- 24277455
TI  - Dual targeting of EWS-FLI1 activity and the associated DNA damage response with
      trabectedin and SN38 synergistically inhibits Ewing sarcoma cell growth.
AB  - PURPOSE: The goal of this study is to optimize the activity of trabectedin for
      Ewing sarcoma by developing a molecularly targeted combination therapy.
      EXPERIMENTAL DESIGN: We have recently shown that trabectedin interferes with the
      activity of EWS-FLI1 in Ewing sarcoma cells. In this report, we build on this
      work to develop a trabectedin-based combination therapy with improved EWS-FLI1
      suppression that also targets the drug-associated DNA damage to Ewing sarcoma
      cells. RESULTS: We demonstrate by siRNA experiments that EWS-FLI1 drives the
      expression of the Werner syndrome protein (WRN) in Ewing sarcoma cells. Because
      WRN-deficient cells are known to be hypersensitive to camptothecins, we utilize
      trabectedin to block EWS-FLI1 activity, suppress WRN expression, and selectively
      sensitize Ewing sarcoma cells to the DNA-damaging effects of SN38. We show that
      trabectedin and SN38 are synergistic, demonstrate an increase in DNA double
      strand breaks, an accumulation of cells in S-phase and a low picomolar IC50. In
      addition, SN38 cooperates with trabectedin to augment the suppression of EWS-FLI1
      downstream targets, leading to an improved therapeutic index in vivo. These
      effects translate into the marked regression of two Ewing sarcoma xenografts at a
      fraction of the dose of camptothecin used in other xenograft studies.
      CONCLUSIONS: These results provide the basis and rationale for translating this
      drug combination to the clinic. In addition, the study highlights an approach
      that utilizes a targeted agent to interfere with an oncogenic transcription
      factor and then exploits the resulting changes in gene expression to develop a
      molecularly targeted combination therapy.

PMID- 24277456
TI  - The PDGFRbeta-AKT pathway contributes to CDDP-acquired resistance in testicular
      germ cell tumors.
AB  - PURPOSE: We examined whether PI3K-AKT or extracellular signal-regulated kinase
      (ERK) signaling pathways could play a role in the development of cisplatin (CDDP)
      resistance in testicular germ cell tumor (TGT) cells. EXPERIMENTAL DESIGN: We
      compared AKT and ERK activation levels in CDDP-sensitive testicular tumor cells
      and in their corresponding CDDP-resistant-derived cells. We also analyzed these
      pathways in orthotopic testicular tumors and human patient samples. RESULTS: Our
      results indicated that there was overactivation of AKT in CDDP-resistant cells
      compared with sensitive cells, but no effect on activated ERK levels. We observed
      an increase in mRNA and protein levels for platelet-derived growth factor (PDGF)
      receptor beta and PDGF-B ligand. These were responsible for AKT overactivation in
      CDDP-resistant cells. When PDGFRbeta levels were decreased by short hairpin RNA
      (shRNA) treatment or its activation was blocked by pazopanib, CDDP-resistant
      cells behaved like sensitive cells. Moreover, CDDP-resistant cells were more
      sensitive to incubation with PDGFRbeta inhibitors such as pazopanib or sunitinib
      than sensitive cells, a finding consistent with these cells being dependent on
      this signaling pathway. We also found overexpression of PDGFRbeta and pAKT in
      CDDP-resistant choriocarcinoma orthotopic tumor versus their CDDP-sensitive
      counterparts. Finally, we found high PDGFRbeta levels in human testicular tumors,
      and overexpression in CDDP-resistant testicular choriocarcinomas compared with
      the CDDP-sensitive and nontreated tumors. CONCLUSIONS: The PDGFRbeta-AKT pathway
      plays a critical role in the development of CDDP resistance in testicular tumoral
      cells.

PMID- 24277457
TI  - Common and complex Notch1 mutations in Chinese oral squamous cell carcinoma.
AB  - PURPOSE: To determine Notch1 mutation status in oral squamous cell carcinoma
      (OSCC) from Chinese population and its potential clinical implications.
      EXPERIMENTAL DESIGN: Surgically resected OSCC tissues from 51 Chinese patients
      and 13 head and neck squamous cell carcinoma (HNSCC) cell lines were sequenced
      for mutations in the entire coding regions of Notch1 and TP53 using a next
      generation sequencing platform. Sequences of the genes were also determined in
      corresponding normal tissues from 46 of the 51 patients. Mutations and their
      association with clinical parameters were analyzed. RESULTS: Six mutations in
      Notch1 and 11 mutations in TP53 coding regions were detected in 4 (31%) and 10
      (77%) of the 13 HNSCC cell lines, respectively. Forty-two somatic Notch1
      mutations, including 7 nonsense mutations and 11 mutations within the domain
      commonly harboring potential activating mutations in acute lymphoblastic
      leukemia, were detected in 22 (43%) of the 51 Chinese OSCC tumors. In comparison,
      25 somatic TP53 mutations were observed in 21 (41%) of the 51 tumors. Patients
      whose tumors carried Notch1 mutation had significantly shorter overall and
      disease-free survivals (P = 0.004 and P = 0.001, respectively, by log-rank test)
      compared with those whose tumors carried no Notch1 mutation. Multivariate
      analysis showed that both Notch1 mutation and lymph node metastasis are
      independent prognostic factors in the patient population (P = 0.001). All 15
      patients with both Notch1 mutation and nodal metastasis recurred or metastasized
      within 2 years after surgery. CONCLUSIONS: Notch1 mutation is common in Chinese
      OSCC and associates with clinical outcomes. The complexity of the mutation
      spectrum warrants further investigation of Notch1 in Chinese patients with OSCC.

PMID- 24277458
TI  - Insertion of the precursor of the light-harvesting chlorophylla/b-protein into
      the thylakoids requires the presence of a developmentally regulated stromal
      factor.
AB  - The precursor of the major light-harvesting chlorophylla/b-proteins of
      photosystem II was synthesizedin vitro from a gene fromLemna gibba. When the
      labelled precursor was incubated with developing barley plastids, the precursor
      and the processed polypeptide were incorporated in the thylakoids in proportions
      that varied depending on the developmental stage of plastids. At early stages of
      development most of the precursor associated with the thylakoids could be removed
      by washing with 0.1 M NaOH, while in more mature plastids most of its was
      resistant to a NaOH wash. Insertion of the precursor into thylakoids required the
      presence of a stromal factor and Mg-ATP. The stromal factor is probably a
      protein. The insertion reaction has an optimal temperature of 25 degrees C and a
      pH of 8. The appearance of the stromal factor and the thylakoid membrane's
      receptivity for the insertion of the precursor depended on the stage of plastid
      development. These observations are consistent with the hypothesis that the
      insertion of the precursor into the thylakoid prior to its proteolytic
      processing, is one of the steps involved in the assembly of the light-harvesting
      complex of photosystem II. 

PMID- 24277459
TI  - APhaseolus vulgaris mitochondrial tRNA(Leu) is identical to its cytoplasmic
      counterpart: sequencing andin vivo transcription of the gene corresponding to the
      cytoplasmic tRNA(Leu.).
AB  - We report here that the sequence ofP. vulgaris mitochondrial and cytoplasmic
      tRNA(Leu) (NAA) are identical except for a post-transcriptional modification.
      There is an unidentified modification at the "wobble" position which, from the
      sequence of the nuclear tRNA(Leu) gene, we identify as a derivative of C. We also
      show that thisP. vulgaris nuclear gene is functional by demonstrating its
      transcription in anin vivo eukaryotic transcription system. 

PMID- 24277460
TI  - Phytochrome regulation of mRNA levels of ribulose-1,5-bisphosphate carboxylase in
      etiolated rye seedlings (Secale cereale).
AB  - The effect of red light and far-red light on the appearance of mRNA for the small
      and large subunit of ribulose-1,5-bisphosphate carboxylase in rye seedlings has
      been analysed. Irradiation of etiolated seedlings with a pulse of red light
      increased the mRNA level of the small subunit by a factor of 7-10 and that of the
      large subunit by a factor of 3. A pulse of far-red light resulted in a much
      lower, but measurable increase. The effect of red light is reverted by an
      immediate far-red pulse, demonstrating the classical phytochrome response.In
      vitro transcription experiments with nuclei isolated from red light-treated
      seedlings showed that the transcription rate of the small subunit mRNA was
      increased only by a factor of 1.5-2.5, indicating posttranscriptional as wells as
      transcriptional regulations of the small subunit of ribulose-1,5-bisphosphate
      carboxylase. 

PMID- 24277461
TI  - Isolation and sequence of cDNA encoding the soybean protease inhibitors PI IV and
      C-II.
AB  - Two full-length (or nearly so) cDNA clones containing information for the
      protease inhibitors PI IV and C-II from soybean seeds were identified by means of
      a synthetic probe. DNA sequencing revealed that the two protease inhibitors are
      synthesized as precursors with a short peptide leader. The coding regions of the
      two clones show 80% homology, wheraes the 5' non-coding regions are 90%
      homologous. Homology of 75% is found in the region extending beyond the stop
      codons. 

PMID- 24277462
TI  - Transient gene expression in electroporated protoplasts and intact cells of sugar
      beet.
AB  - Factors influencing the transient expression of introduced foreign DNA in
      electroporated protoplasts and intact cells of sugar beet were determined by
      assaying for the activity of chloramphenicol acetyltransferase (CAT), using a
      rectangular pulse generating system. Extractable CAT activity depended upon 1)
      applied plasmid DNA concentration, 2) protoplast density, 3) the interaction
      between pulse field strength, duration, number, time interval between pulses and
      the resultant effect on culture viability, and 4) the physiological state of the
      protoplasts. Mesophyll protoplasts were more susceptible to damage by
      electroporation, and were more specific in their requirement for electroporations
      which allowed CAT expression, than were protoplasts derived from suspension
      culture cells. CAT activity was also demonstrated, at low levels, after
      electroporation of intact suspension culture cells, and could be increased by
      pectinase treatment of the cells before electroporation. 

PMID- 24277463
TI  - Sequence organization of the chloroplast ribosomal spacer ofSpinacia oleracea
      including the 3' end of the 16S rRNA and the 5' end of the 23S rRNA.
AB  - The 2201-bp spacer between the chloroplast ribosomal 16S and 23S genes ofSpinacia
      oleracea was sequenced. It contains the genes of the tRNA(Ile) (GAU) and
      tRNA(Ala) (UGC) which are both interrupted by introns of respectively 728 and 816
      bp. These introns belong to the class II according to the classfication of Michel
      and Dujon [17]. Comparison of the rDNA spacer sequence of maize, tobacco and
      spinach indicates that no conserved polypeptide is encoded within the introns of
      the two tRNA genes and that the two main insertions/deletions between the three
      plants are located within two loops of the class II introns secondary structure,
      which is therefore conserved. Based on the sequence complementarity observed
      between the upstream and downstream parts, of the 16S and 23S rRNA genes, RNase
      III-like secondary structures involved in the processing of the rRNA precursor
      are proposed. 

PMID- 24277464
TI  - Sequence studies on the soybean chloroplast 16S-23S rDNA spacer region :
      Comparison with other angiosperm sequences and proposal of a generalized RNA
      secondary structure model for the intergenic regions.
AB  - The sequence of the ribosomal spacer region of soybean chloroplast DNA including
      the 3' end of the 16S rRNA gene, the tRNA(Ala) and tRNA(Ile) genes (but not their
      introns), the three intergenic regions and the 5' end of the 23S rRNA gene, has
      been determined. This sequence has been compared to corresponding regions of
      other angiosperm chloroplast DNAs. Secondary structure models are proposed for
      the entirety of the intergenic regions a, b and c and for the flanking rRNA
      regions. A model for a common secondary structure of the ribosomal spacer
      intergenic regions from chloroplasts of higher plants is proposed, which is
      supported by comparative evidence. 

PMID- 24277465
TI  - The expression and prognosis of Emi1 and Skp2 in breast carcinoma: associated
      with PI3K/Akt pathway and cell proliferation.
AB  - S-phase kinase protein 2 (Skp2) is oncogenic and overexpressed in human breast
      cancer. The objective of this study was to examine the effect of early mitotic
      inhibitor-1 (Emi1) over-expression on Skp2 expression and related signaling
      pathway in breast cancer. Immunohistochemical analysis was performed in 98 human
      breast carcinoma samples and the data were correlated with clinicopathologic
      features. Furthermore, Western blot analysis was performed for Emi1 and Skp2 in
      breast carcinoma samples and cell lines to evaluate their protein levels and
      molecular interaction. We found that the expression of Emi1 was positively
      related with Skp2 expression (P < 0.01) and Emi1 expression correlated
      significantly with histologic grade (P = 0.005), meanwhile Skp2 expression
      obtained similar results. Kaplan-Meier analysis revealed that survival curves of
      low versus high expressers of Emi1 and Skp2 showed a highly significant
      separation in human breast cancer (P < 0.01). While in vitro, following release
      of breast cancer cell lines from serum starvation, the expression of Emi1, Skp2,
      phosphor-Akt (p-Akt) was up-regulated, whereas p27(Kip1) was down-regulated.
      Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could arrest
      cells growth and diminish Emi1 expression. These results suggested that Emi1's
      anti-apoptotic and proliferative abilities appear to be triggered at least in
      part by the modulation of Skp2, combined Emi1 and Skp2 expressions, may be
      prognostic for patients with invasive breast carcinomas, which also associated
      with p-Akt and enabled p27(kip1) degradation. Emi1 may serve as a potential
      therapeutic strategy aimed at PI3K for the management of breast cancer. 

PMID- 24277467
TI  - Leucocytes isolated from simply frozen whole blood can be used in human
      biomonitoring for DNA damage measurement with the comet assay.
AB  - Preservation of human blood cells for DNA damage analysis with the comet assay
      conventionally involves the isolation of mononuclear cells by centrifugation,
      suspension in freezing medium and slow freezing to -80  degrees C-a laborious
      process. A recent publication (Al-Salmani et al. Free Rad Biol Med 2011; 51: 719
      725) describes a simple method in which small volumes of whole blood are frozen
      to -20 or -80  degrees C; on subsequent thawing, the comet assay is performed,
      with no indication of elevated DNA strand breakage resulting from the rapid
      freezing. However, leucocytes in whole blood (whether fresh or frozen) are
      abnormally resistant to damage by H2 O2 , and so a common test of antioxidant
      status (resistance to strand breakage by H2 O2 ) cannot be used. We have refined
      this method by separating the leucocytes from the thawed blood; we find that,
      after three washes, the cells respond normally to H2 O2 . In addition, we have
      measured specific endogenous base damage (oxidized purines) in the isolated
      leucocytes, using the enzyme formamidopyrimidine DNA glycosylase. In a study of
      blood samples from 10 subjects, H2 O2 sensitivity and endogenous damage-both
      reflecting the antioxidant status of the cells-correlated significantly. This
      modified approach to sample collection and storage is particularly applicable
      when the available volume of blood is limited and has great potential in
      biomonitoring and ecogenotoxicology studies where samples are obtained in the
      field or at sites remote from the testing laboratory.

PMID- 24277466
TI  - Investigation on XRCC1 genetic polymorphism and its relationship with breast
      cancer risk factors in Chinese women.
AB  - Breast cancer (BC) remains one of the most common cancers among women. The human
      X-ray repair cross-complementing 1 (XRCC1) gene plays key roles in base excision
      repair, and genetic polymorphisms of XRCC1 may be associated with the
      susceptibility to BC. This study aimed to evaluate the relationship between the
      XRCC1 genetic polymorphisms and BC susceptibility. A total of 354 BC patients and
      366 cancer-free controls were enrolled in this study. Data about the risk factors
      of BC were collected using questionnaires. The XRCC1 genetic polymorphism was
      determined using created restriction site-polymerase chain reaction (CRS-PCR) and
      DNA sequencing methods. No significant differences in the allelic and genotypic
      frequencies of c.1804C>A genetic polymorphism were detected between cases and
      controls. The distributions of BC patients' risk factors were not significantly
      different between CC, CA, and AA genotypes. These findings indicate that the
      c.1804C>A genetic polymorphism of XRCC1 gene is not significantly associated with
      BC susceptibility in the Chinese women. 

PMID- 24277468
TI  - Television, teenagers, and health.
AB  - The purpose of this study was to determine the extent to which multiple health
      and lifestyle variables differ among 406 adolescent males classified according to
      average duration of daily television viewing. Cattell's 16PF Questionnaire, Form
      C, and Rosenberg's Self-Esteem Scale were employed to assess psychological
      health, and the Physical Performance Test for California was used to measure six
      dimensions of physical fitness. Participants also completed a questionnaire
      requesting general demographic data, and information regarding lifestyle and
      average amount of time spent watching television per day. Results indicated that
      the well-being of the boys was related significantly to the extent of television
      viewing. Light television viewers were more physically fit, emotionally stable,
      sensitive, imaginative, outgoing, physically active, self-controlled,
      intelligent, moralistic, college bound, church oriented, and self-confident than
      their counterparts, especially heavy television viewers. Furthermore, light
      television viewers were less troubled, frustrated, and shrewd, and used drugs
      less frequently, particularly alcohol, than moderate and heavy television
      watchers, especially the latter. 

PMID- 24277469
TI  - The inventory of parent and peer attachment: Individual differences and their
      relationship to psychological well-being in adolescence.
AB  - The results of two studies are reported. Study I involved the development of the
      Inventory of Parent and Peer Attachment (IPPA), a self-report instrument for use
      with adolescents. Subject were 179 college students aged 16-20 years. Item
      content of the instrument was suggested by attachment theory's formulations
      concerning the nature of feelings toward attachment figures. In Study II, the
      convergent validity of the IPPA was examined. Also, a hierarchial regression
      model was employed to investigate the association between quality of attachment
      and self-esteem, life-satisfaction, and affective status. Respondents were 86
      adolescents from the Study I sample. As hypothesized, perceived quality of both
      parent and peer attachments was significantly related to psychological well
      being. Results of the development of a theoretically focused, exploratory
      classification scheme indicated that adolescents classified as highly securely
      attached reported greater satisfaction with themselves, a higher likelihood of
      seeking social support, and less symptomatic response to stressful life events. 

PMID- 24277470
TI  - Israeli adolescents' self-image profile.
AB  - Seven hundred and seventy-two Jewish Israeli male and female high school students
      (aged 14-18) responded to a Hebrew version of the Offer Self-Image Questionnaire
      (OSIQ). Results show that, much like the American adolescents, the majority of
      the Israeli respondents are happy and well-adjusted, although a noticeable
      minority experiences some personal trouble. Gender and age differences show that
      males hold a more positive self-image than do females, and that age differences
      among males are larger than among females. Comparisons with the American norm
      sample indicate that the Israeli and American self-image profiles differ
      significantly on only three scales. Israelis report a higher impluse control, and
      lower morals and vocational and educational goals. These results are discussed in
      terms of ecological and cultural explanations, and the need for extending OSIQ
      research to additional sectors of Israeli society is noted. 

PMID- 24277471
TI  - The effect of parental divorce on parent-adolescent separation.
AB  - The purpose of this study was to identify variables that differentially affect
      parent-adolescent separation in subjects from separated vs subjects from intact
      families. The subjects were 318 introductory psychology students at the
      University of Manitoba who had already left home. They were given the Moving Out
      questionnaire as well as Rotter's Internal-External Locus of Control Scale.
      Contrary to our hypotheses, subjects from separated families did not experience
      more conflict when leaving home than subjects from intact families, and the type
      and amount of divorce-related conflict was not related to higher emotional
      separation or locus of control scores. However, it was found that as divorce
      related conflict became more openly expressed, feelings of personal control
      increased and feelings about leaving home became more positive. Emotional
      separation scores were significantly higher for all males and for subjects from
      separated families. Also, females had a greater sense of external control than
      males. 

PMID- 24277472
TI  - Direct probing of charge injection and polarization-controlled ionic mobility on
      ferroelectric LiNbO(3) surfaces.
AB  - Mapping surface potential with time-resolved Kelvin probe force microscopy (tr
      KPFM) in LiNbO3 periodically poled single crystals reveals activation of the
      surface ionic subsystem. Electric fields of certain strength induce injection of
      charge, formation of an active region in its vicinity and uneven distribution of
      screening charge on the opposite ferroelectric domains. Tr-KPFM technique allows
      investigating these phenomena in details. 

PMID- 24277473
TI  - siRNA-mediated knock-down of DFF45 amplifies doxorubicin therapeutic effects in
      breast cancer cells.
AB  - PURPOSE: RNA interference (RNAi) has become a promising tool for cancer therapy.
      Small interfering RNAs (siRNAs) can synergistically enhance the cell killing
      effects of drugs used in cancer treatment. Here we examined the effects of siRNA
      mediated DNA fragmentation factor 45 (DFF45) gene silencing on breast cancer cell
      viability, cell cycle arrest, and apoptosis in the presence and absence of
      doxorubicin. METHODS: We designed three siRNAs, which target different regions of
      the DFF45 mRNA. Gene silencing was confirmed by real time RT-PCR and Western blot
      analyses. The impact of DFF45 siRNA, doxorubicin, and their combination on the
      viability, cell cycle and apoptosis of T-47D and MDA-MB-231 breast cancer cells
      were determined by MTT, PI staining, annexin V binding, caspase-3 activity, DNA
      laddering, and chromatin condensation assays. RESULTS: Based on flow cytometric
      analyses, we found that silencing of DFF45 alone had little effect on apoptosis,
      especially in T-47D cells. However, when used in combination with doxorubicin
      (0.33 MUM) a significant increase (P < 0.05) in apoptosis was observed in T-47D
      and MDA-MB-231 cells, i.e., ~2.5- and 3-fold, respectively. Caspase-3 activity,
      chromatin condensation, as well as DNA laddering supported increased apoptosis in
      the combinatorial treatment. Cell cycle arrest in both cell lines occurred at
      lower levels after siRNA + doxorubicin treatment compared to doxorubicin only.
      CONCLUSIONS: Our data indicate that DFF45 gene silencing, when applied in
      combination with doxorubicin, may offer a novel therapeutic strategy for the
      treatment of breast cancer.

PMID- 24277474
TI  - Thymidylate synthase expression and p21(WAF1)/p53 phenotype of colon cancers
      identify patients who may benefit from 5-fluorouracil based therapy.
AB  - BACKGROUND: Studies on the expression of thymidylate synthase (TS) in colorectal
      cancers (CRCs) have failed to provide unequivocal prognostic or predictive
      information. Here, we assessed the prognostic significance of TS expression in
      Astler-Coller stage B2 and C CRCs defined by a p21(WAF1)/p53 immunophenotype in
      patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy. METHODS: A
      cohort of 189 CRCs was asssessed for TS, p21(WAF1) and p53 expression on tissue
      microarrays using immunohistochemistry, and associations with disease-free
      survival (DFS) and overall survival (OS) of the patients were assessed using
      univariate and multivariate analyses. RESULTS: TS expression led to the
      stratification of patients with colon cancer, but not rectal cancer, with
      immunophenotypes other than p21(WAF1)+/p53- (referred to as P&P) into subgroups
      characterized by a worse (P&P TS+) and a better (P&P TS-) DFS and OS, in
      univariate (P = 0.006 and P = 0.005, respectively) and multivariate (P = 0.0004
      and P = 0.002, respectively) analyses. The p21(WAF1)+/p53- immunophenotype was
      associated with a favorable prognosis, irrespective of TS expression.
      CONCLUSIONS: The strong association observed between the P&P TS+ immunophenotype
      and a worse DFS and OS suggests a predictive significance of TS expression for
      5FU-based adjuvant therapy in patients with colon cancers exhibiting the P&P
      immunophenotype. In addition, our findings suggest that the appropriate target
      for assessment of TS expression as a prognostic/predictive marker is a subgroup
      of colon cancers with an immunophenotype other than p21(WAF1)+/p53-, and that
      only in this subgroup high TS expression is associated with an unfavorable DFS
      and OS. Therefore, we suggest that assessing TS expression in conjunction with
      p21(WAF1)/p53 immunophenotyping of colon cancers may improve the selection of
      patients suitable for 5FU-based adjuvant chemotherapy.

PMID- 24277475
TI  - Increased burden on caregivers of having a child with haemophilia complicated by
      inhibitors.
AB  - INTRODUCTION: Having a child with a chronic disease often increases the burden in
      the family with more hospital visits, treatment administration, and increased
      worries for the ill child. A cross-sectional, international, multi-centre study
      in caregivers of children <18 years with haemophilia and inhibitor was performed
      at Haemophilia Treatment Centres in Sweden, UK, and Canada to evaluate
      caregivers' burden and their health-related quality of life (HRQoL) compared to
      that of caregivers of children on prophylaxis without inhibitors and caregivers
      of healthy children. METHODS: Caregivers of children with haemophilia completed
      several questionnaires (SF-36, Visual Analogue Scale of Interference (VAS),
      Caregivers' Burden Scale and Impact on Family Scale (IOF). Caregivers of healthy
      children completed only the SF-36. In addition, socio-demographic data were
      collected. RESULTS: In total, 143 caregivers were included in the study.
      Comparing the two haemophilia groups with caregivers of healthy children revealed
      significant differences for all SF-34 domains except 'pain' and 'general health'.
      In Caregivers' Burden Scale, caregivers of children with inhibitors reported
      higher impact of haemophilia (P < 0.0001) and higher impact on VAS (P < 0.0001)
      compared to caregivers of children without inhibitors. In IOF, caregivers of
      children with inhibitors reported significant negative impact of the disease,
      except for aspect of coping. CONCLUSION: Caregivers of children with inhibitors
      reported higher impact of the disease compared to caregivers of children with no
      inhibitors. No differences between mothers and fathers in the two groups for SF
      36, Caregivers' Burden Scale, VAS and IOF, except for domain pain in SF-36 where
      mothers reported higher impairments.

PMID- 24277476
TI  - Primary prevention and the family: Part II.

PMID- 24277477
TI  - Adaptation to parenthood: Differing expectations of social supports for mothers
      versus fathers.
AB  - One hundred and twenty-three first-time parent-couples of five-month-old infants
      were studied to determine the relationship between dyadic adjustment and marital
      satisfaction and selected social supports. The identification of need for
      support, the utilization of support, and the satisfaction with those supports
      utilized for both child care and household tasks were examined. Mothers and
      fathers responded separately to Guerney'sRelationship Change Scale,
      Spanier'sDyadic Adjustment Scale, and to a demographic and social support
      inventory. One finding was that factors promoting satisfactory marital adjustment
      were different for new mothers and new fathers. In particular, social supports
      for child care and household tasks were related to a satisfying adjustment only
      in new mothers, following culturally stereotypic delineation of concerns. 

PMID- 24277478
TI  - Child-rearing strategies for the development of altruistic behavior in young
      children.
AB  - Research findings concerning child-rearing strategies that encourage the
      development of altruistic behavior in young children from infancy to age six are
      incorporated in a workshop series for families. The workshops are designed to
      educate and influence the adult-child interaction on cognitive, behavioral, and
      affective levels. They have been developed for implementation by nonprofessionals
      in groups involved or interested in parent education and the care, guidance, and
      training of young children. The structure of the workshops emphasizes
      participation, role-playing, practice of skills, and discussion of experiences
      and values by the participants. The workshop content emphasizes an ecological
      approach that has been demonstrated to form a basis for encouraging helping,
      sharing, and comforting behaviors in young children. 

PMID- 24277479
TI  - Preventive screening of adolescent mothers and infants: Critical variables in
      assessing risk for child maltreatment.
AB  - One hundred, ninety adolescent mother-infant dyads judged to be at extreme risk
      for relationship failure and possible child maltreatment were assessed by a
      trained nurse/social worker team within 24 hours of delivery of the infant. The
      statewide Central Registry of child maltreatment reports was later examined to
      learn which mothers had been reported since the initial assessment 12 to 27
      months earlier. The subsamples of this resulted in 172 Non-CPS mother-infant
      dyads and in 18 CPS-involved mother-infant dyads. Comparison of differences
      revealed that the key signals of risk were the personal, environmental, and
      educational isolations from those elements critical to the successful rearing of
      a child. Necessary, but absent, elements of successful maternal-infant
      relationship were found to include: knowledge of child care techniques and
      alternatives discipline and parent-skills; more appropriate assessments of mother
      infant dyads; and greater social support for the mother's seeking and finding
      other appropriate child care helpers. 

PMID- 24277480
TI  - Helping teenage parents: Use of age-paced parent education newsletters.
AB  - Although many school systems have developed programs to meet the special needs of
      school age parents, the norm continues to be school dropout for adolescent girls
      who become pregnant. Because these girls and their children are at high risk for
      problems, Cooperative Extension throughout the United States has created
      instructional material specifically aimed at preventing psychosocial and
      developmental problems among an audience of very young mothers. This article
      describes the considerations and formats of newsletters for young parents,
      originating in California and Washington through Cooperative Extension in those
      states. 

PMID- 24277481
TI  - Regulation of macrophage biology by lithium: a new look at an old drug.
AB  - Lithium (Li) continues to be a standard small compound used for the treatment of
      neurological disorders. Besides neuronal cells, Li is also known to affect immune
      cell function. In spite of its clinical use, potential mechanisms by which Li
      modulates immune cells, especially macrophages and its clinical relevance in
      bipolar patients are not well understood. Here, we provide an overview of the
      literature with regard to Li's effects on monocytes and macrophages. We have also
      included some of our results showing that Li differentially modulates chemokine
      gene expression in the absence and presence of Toll-like receptor-4 stimulation
      in a human macrophage model. Given that Li has a wide range of intracellular
      targets both in macrophages as well as in other cell types, more studies are
      needed to further understand the mechanistic basis of Li's effect in neurological
      and other inflammatory diseases. These studies could undoubtedly identify new
      therapeutic targets for treating such diseases. 

PMID- 24277483
TI  - Disorders of hemostasis in overt and subclinical hypercortisolism.
AB  - Glucocorticoids are a group of hormones of a particular impact on hemostasis.
      Epidemiological studies show an approximately severalfold greater incidence of
      thromboembolic events in hypercortisolemic patients compared to those without
      hormonal disorders. The prothrombotic action of this steroid class is caused by
      both the direct impact of hypercortisolism on the activation of coagulation and
      the inhibition of fibrinolysis, as well as, the pathology of hemostasis due to
      metabolic disorders, which occur in this endocrinopathy. The aim of this study
      was to discuss the hemostasis abnormalities that occur in patients with overt and
      subclinical hypercortisolism with a particular emphasis on plasmatic coagulation,
      endogenous anticoagulation system, homocysteine and proinflammatory cytokines. 

PMID- 24277482
TI  - TNF-alpha/NF-kappaB signaling in the CNS: possible connection to EPHB2.
AB  - Tumor necrosis factor-alpha, TNF-alpha, is a cytokine that is a well-known factor
      in multiple disease conditions and is recognized for its major role in central
      nervous system signaling. TNF-alpha signaling is most commonly associated with
      neurotoxicity, but in some conditions it has been found to be neuroprotective.
      TNF-alpha has long been known to induce nuclear factor-kappa B, NF-kappaB,
      signaling by, in most cases, translocating the p65 (RelA) DNA binding factor to
      the nucleus. p65 is a key member of NF-kappaB, which is well established as a
      family of transcription factors that regulates many signaling events, including
      growth and process development, in neuronal cell populations. NF-kappaB has been
      shown to affect both the receiving aspect of neuronal signaling events in
      dendritic development as well as the sending of neuronal signals in axonal
      development. In both cases, NK-kappaB functions as a promoter and/or inhibitor of
      growth, depending on the environmental conditions and signaling cascade. In
      addition, NF-kappaB is involved in memory formation or neurogenesis, depending on
      the region of the brain in which the signaling occurs. The ephrin (Eph) receptor
      family represents a subfamily of receptor tyrosine kinases, RTKs, which received
      much attention due to its potential involvement in neuronal cell health and
      function. There are two subsets of ephrin receptors, Eph A and Eph B, each with
      distinct functions in cardiovascular and skeletal development and axon guidance
      and synaptic plasticity. The presence of multiple binding sites for NF-kappaB
      within the regulatory region of EphB2 gene and its potential regulation by NF
      kappaB pathway suggests that TNF-alpha may modulate EphB2 via NF-kappaB and that
      this may contribute to the neuroprotective activity of TNF-alpha. 

PMID- 24277484
TI  - p21 is associated with the proliferation and apoptosis of bone marrow-derived
      mesenchymal stem cells from non-obese diabetic mice.
AB  - Recent studies have shown that autologous and allogeneic transplantation of the
      BM-MSCs had therapeutic effects on T1DM, whereas the BM-MSCs from the NOD mice
      itself did not have this therapeutic effect. We previously demonstrated that Bone
      Marrow (BM) -MSCs from the non-obese diabetic (NOD) mice had the abnormal
      migration and adhesion. So we hypothesized that the proliferation and apoptosis
      of the BM-MSCs from the NOD mice were dysregulated. Our team compared the
      proliferation and apoptosis between NOD mice and imprinting control region (ICR)
      mice. Then we assessed whether the NF-kappaB-p53/p21 pathway was involved in the
      process. The cell proliferation ability of the BM-MSCs from the NOD mice were
      significantly decreased, while the percent of apoptotic cells was increased
      compared to those from the ICR mice. The p21 expression was significantly
      increased in the NOD-MSCs. The p65 level was enhanced in the BM-MSCs from the NOD
      mice when compared to the ICR mice, coincided with the expression of p21.
      Expressions of p65 and p21 were significantly decreased in the -BM-MSCs treated
      with p65 inhibitor. The knockdown p21 expression reversed the abnormal
      proliferation, colony formation and apoptosis of the BM-MSCs from the NOD mice.
      These data provide important preclinical references supporting the basis for
      further development of autologous MSC-based therapies for type1 diabetes mellitus
      (T1DM). 

PMID- 24277485
TI  - High frequency of non-nocturnal hypoglycemia was associated with poor sleep
      quality measure by Pittsburg Sleep Quality Index in patients with diabetes
      receiving insulin therapy: Diabetes Distress and Care Registry at Tenri (DDCRT
      4).
AB  - To investigate the temporal association between frequency of non-nocturnal
      hypoglycemia and sleep quality among patients with diabetes receiving insulin
      therapy.We used data from 1 513 patients with diabetes receiving insulin therapy.
      We estimated the relative risks (RR) of the frequency of non-nocturnal
      hypoglycemia for poor sleep quality measured by the Pittsburgh Sleep Quality
      Index.The average age and HbA1c value of the patients were 63.7 years and 7.8%,
      respectively. Compared with poor sleep quality in patients without any type of
      non-nocturnal disabling hypoglycemia (NNDH), the multivariable-adjusted RR values
      for poor sleep quality were 1.30 (95% confidence interval [CI], 1.06-1.61) and
      1.37 (95% CI, 0.96-1.95) in patients who experienced 1-4 and >=5 episodes of
      NNDH, respectively (p=0.004). Experiencing non-nocturnal severe hypoglycemia
      (NNSH) once in the past 90 days significantly increased the risk of poor sleep
      quality by 1.54 episodes (95% CI, 1.16-2.05; p=0.003). By adding the presence of
      depression as a variable to the multivariable-adjusted model, these associations
      were attenuated because we did not observe any significant association between
      NNDH and poor sleep quality (p=0.178). However, a significant association between
      NNSH and poor sleep quality was observed (RR=1.43; 95% CI, 1.09-1.90; p=0.011).A
      high frequency of non-nocturnal hypoglycemia was associated with poor sleep
      quality in patients with diabetes receiving insulin therapy. Our data also
      suggested that the association of NNDH, and not NNSH, was mediated by comorbid
      depression. 

PMID- 24277486
TI  - Fabrication of ordered, large scale, horizontally-aligned si nanowire arrays
      based on an in situ hard mask block copolymer approach.
AB  - A simple technique is demonstrated to fabricate horizontal, uniform, and
      hexagonally arranged Sinanowire arrays with controlled orientation and density at
      spatially well defined locations on a substrate based on an in situ hard-mask
      pattern-formation approach by microphase-separated block-copolymer thin films.
      The technique may have significant application in the manufacture of transistor
      circuitry. 

PMID- 24277487
TI  - 5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms:
      genotype frequency and association with homocysteine and folate levels in middle
      southern Italian adults.
AB  - Two genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene
      (C677T and A1298C) can influence the plasma homocysteine (Hcy) levels, especially
      in the presence of an inadequate folate status. The aim of this study was to
      evaluate the frequencies of C677T and of A1298C MTHFR polymorphisms and their
      correlation with Hcy and serum folate concentrations in a population of blood
      donors living in a region of middle-southern Italy (the Molise Region). One
      hundred ninety seven blood donors were studied for total plasma Hcy, serum folate
      and C677T and A1298C MTHFR genotypes. The frequency of C677T genotypes was 20.8%
      (CC), 49.8% (CT) and 29.4% (TT); for the A1298C genotypes: 48.7% (AA), 43.7% (AC)
      and 7.6% (CC). Hcy and serum folate concentrations were significantly different
      among genotypes of the C677T polymorphism (CC versus CT versus TT: <0.0001 both
      for Hcy and folate), with Hcy values increasing, and serum folate decreasing,
      from CC to TT subjects. Regarding to A1298C polymorphism, the difference among
      genotypes (AA versus AC versus CC; p: 0.026 for Hcy and 0.014 for serum folate),
      showed an opposite trend for both parameters, with Hcy higher in the wild-type
      and lower in the homozygotes and serum folate higher in CC than in AA subjects.
      In conclusion, we found a high frequency of MTHFR allele associated with high
      level of Hcy and low levels of folate in an Italian southern population.

PMID- 24277488
TI  - Adolescent response to the death of a parent.
AB  - Participants in the present study, while between the ages of 12 and 19, had a
      parent die. The death had occurred not less than 6 months and not more than 5
      years prior to psychological testing and interview. The effects of loss, as
      assessed by the Beck Depression Inventory and other measures, were considered in
      relation to a number of independent factors. Factors found to influence healthy
      adaptation included high levels of informal social support postloss, good
      relations with the surviving parent prior to loss, a balanced personality style,
      and presence of religious beliefs. 

PMID- 24277489
TI  - Stereotypes of social isolation and early burnout in the gifted: Do they still
      exist?
AB  - At the turn of the century, two common stereotypes of genius were that precocity
      was associated with social failure and that precocity bred early burnout. Later
      research on the gifted has refuted these stereotypes. The two studies in this
      paper investigate whether the stereotypes have changed in light of this new
      knowledge. In the first study, 66 male and 61 female colege students rated
      gifted, able, and average males and females. In the second study, 60 male and 59
      female college students rated males and females with various extreme levels of
      precocity. In both studies, the stimulus persons were rated as high schoolers and
      as adults. Results indicate that the perception of the gifted, especially
      females, as encountering serious social problems is still prevalent. The illusion
      of burnout, however, has been replaced with an illusion of unqualified success. 

PMID- 24277490
TI  - Do economic conditions influence how theorists view adolescents?
AB  - Eighty-nine articles in thePedagogical Seminary and theJournal of Genetic
      Psychology appearing during two economic depressions and the two world wars were
      analyzed for their adolescent ideologies. A systematic, ideological bias in the
      content of these articles was found to be statistically significant. In times of
      economic depression theories of adolescence emerge that portray teenagers as
      immature, psychologically unstable, and in need of prolonged participation in the
      educational system. During wartime, the psychological competence of youth is
      emphasized and the duration of education is recommended to be more retracted than
      in depression. The objective, scientific nature of theory building is questioned
      and discussed. 

PMID- 24277491
TI  - Lonelines in pre-through late adolescence: Exploring the contributions of a
      multidimensional approach.
AB  - A multidimensional loneliness measure was administered to 444 subjects in the 11
      17 age range. The four-scale instrument probes for loneliness in relationships
      with parents and peers, and for aversion to and affinity for aloneness. All
      subscales were shown to exhibit high reliability and excellent factorial
      validity. With regard to age effects, a marginally significant increase was found
      for parent-related loneliness, accompanied by a sudden drop at the seventh-grade
      level. A decreasing age trend emerged in both peer-related loneliness and
      aversion to aloneness. A set of variables pertaining to subjects' social
      integration (number of friends, quality of friendships) and psychological
      functioning (outlook on the future) accounted for a sizable portion of the
      variance in all four scales, particularly in peer-related loneliness.
      Implications of these findings are discussed and suggestions for future research
      are outlined. 

PMID- 24277492
TI  - Adolescents' evaluations of Peers' motives for helping.
AB  - Four groups of high-school students (N=92) were each informed about a pair of
      helpers, either male or female, who independently helped a sameor opposite-sex
      peer. Within each pair of same-sex helpers, one was presented as having helped
      for empathic reasons and the other was presented as having helped for nonempathic
      reasons. The adolescents' ratings of the helpers indicated that they generally
      favored empathically motivated helping in both male and female peers. However, a
      female helper who did not express sensitivity and emotional responsiveness to the
      feelings of the needy other in her prosocial moral reasoning tended to be judged
      more harshly by the adolescents than did a male helper who failed to express such
      sentiments. 

PMID- 24277493
TI  - Occupational identity status development, gender comparisons, and internal
      external control in first-year air force cadets.
AB  - This study of cadets at the United States Air Force Academy during their first
      six months assessed the pattern of developmental changes in occupational identity
      status for males and females, examined the relationship of internal-external
      control to identity statuses, and discussed the data in terms of Erikson's
      proposals and factors involved in gender differences in identity development.
      More than half of the cadets entering the academy were in uncommitted
      occupational identity statuses. Over the time period, half the cadets remained in
      their identity statuses, with the Foreclosed cadets the most stable and Achieved
      the least stable. The expected changes in the Achieved identity status, and other
      changes, established a pattern of identity development congruent with Erikson's
      theory of developmental progress or regression in identity formation. Only male
      cadets demonstrated significant changes into or out of a status, and significant
      associations between their identity statuses and internal-external control, with
      more internally controlled males being Achieved and more externally controlled
      males being Diffused-diffused. 

PMID- 24277494
TI  - Replication and amplification of the small mitochondrial DNAs in a cell
      suspension of Black Mexican Sweet maize.
AB  - The mitochondrial genome of Black Mexican Sweet (BMS) maize includes the
      principal genome and two transcriptionally active minicircular DNAs of 1913 and
      1445 bp. A cell suspension of this line was used to study the biology and
      replication of the minicircular DNAs. Synthesis of the DNAs was measured by (32)P
      incorporation; all mitochondrial DNAs (mtDNAs) were synthesized rapidly during
      logarithmic growth phases, whereas no synthesis could be detected in stationary
      phase. When stationary phase cultures were placed in fresh medium and
      incorporation was measured over time, the 1.9-kb minicircle renewed (32)P
      incorporation prior to incorporation into the 1.4-kb minicircle, the principal
      mitochondrial genome, or the nuclear genome. Interestingly, plastid DNA renewed
      incorporation at the same time as the 1.9-kb minicircle. The early replication of
      the 1.9-kb minicircle relative to the other DNAs increased the copy number of
      this DNA relative to the other mitochondrial DNAs. The copy number of the
      minicircular DNAs also varied between leaf cells and the cell suspension. This
      indicates that components of the mitochondrial genome exhibit differential
      replication. The ability to follow replication of individual mitochondrial
      components makes this system valuable for studies of DNA replication. 

PMID- 24277495
TI  - The relatively large beta-tubulin gene family of Arabidopsis contains a member
      with an unusual transcribed 5' noncoding sequence.
AB  - We have characterized the beta-tubulin gene family of Arabidopsis thaliana. Five
      distinct genes were cloned and analyzed by restriction enzyme mapping and cross
      hybridization studies. Three of the genes appear to be dispersed, whereas two
      others are linked within 1.5 kb of one another. The two linked genes are closely
      related and appear to have resulted from a fairly recent duplication. The three
      dispersed genes do not cross-hybridize to one another or to the two linked genes
      under highly stringent hybridization conditions, suggesting that they arose from
      more ancient duplications. From Southern analysis we estimate that there are a
      total of between six and ten beta-tubulin genes in Arabidopsis. Additional
      analyses indicate that the gene family is equal in size or larger than those in
      other plants, but significantly smaller than those in related Brassica species.
      Sequence determination of one of the Arabidopsis genes revealed a highly unusual
      transcribed leader sequence. The leader contains two fairly long tracks of
      adenines. One is located toward the 5' end of the mRNA and the other is just
      before the initiation codon. A track of uridines is located between the adenine
      tracks. This leader can form two different secondary structures that may have
      regulatory significance. 

PMID- 24277496
TI  - Transformation of cotton (Gossypium hirsutum L.) by Agrobacterium tumefaciens and
      regeneration of transgenic plants.
AB  - Cotton (Gossypium hirsutum L.) cotyledon tissues have been efficiently
      transformed and plants have been regenerated. Cotyledon pieces from 12-day-old
      aseptically germinated seedlings were inoculated with Agrobacterium tumefaciens
      strains containing avirulent Ti (tumor-inducing) plasmids with a chimeric gene
      encoding kanamycin resistance. After three days cocultivation, the cotyledon
      pieces were placed on a callus initiation medium containing kanamycin for
      selection. High frequencies of transformed kanamycin-resistant calli were
      produced, more than 80% of which were induced to form somatic embryos. Somatic
      embryos were germinated, and plants were regenerated and transferred to soil.
      Transformation was confirmed by opine production, kanamycin resistance,
      immunoassay, and DNA blot hybridization. This process for producing transgenic
      cotton plants facilitates transfer of genes of economic importance to cotton. 

PMID- 24277497
TI  - Molecular characterization of two clusters of genes encoding the Type I CAB
      polypeptides of PSII in Nicotiana plumbaginifolia.
AB  - A Nicotiana plumbaginifolia genomic library in the phage Charon 34 was used to
      isolate and characterize 7 full-length genes and part of an 8th gene encoding
      chlorophyll a/b-binding (CAB) polypeptides. These genes are arranged in two
      clusters. All the genes within the clusters are arranged in opposite orientation
      to their neighbours. The nucleotide sequences of two genes, one from each
      cluster, show that both genes, designated Cab-E and Cab-C, encode very similar
      proteins (95.9% of homology) corresponding to type I photosystem II polypeptides.
      Southern blot analysis suggests that at least 19 CAB genes encoding type I PSII
      CAB polypeptides are present in the N. plumbaginifolia genome. We also describe
      the presence within the N. plumbaginifolia genome of CAB genes encoding PSII type
      II CAB polypeptides and PSI type I CAB polypeptides. The sequences of the 5'
      flanking region of three different CAB genes (Cab-E, Cab-C, and CAB-F) were
      determined. Two of them (Cab-C and Cab-F) share extensive homology, whereas the
      Cab-E promoter shows homology to Cab-C and Cab-F only in a unique region
      extending from the CAAT box to the TATA box. This conserved sequence is also
      found in the same position in promoters of CAB genes encoding type I PSII
      polypeptides from other plant species. 

PMID- 24277498
TI  - Characterization of a full-length petunia cDNA encoding a polypeptide of the
      light-harvesting complex associated with photosystem I.
AB  - We have isolated and characterized a full-length cDNA clone (LHCI-15) which
      specifies a new chlorophyll-binding protein. This protein is associated with the
      light-harvesting complex of photosystem I (LHCI). The DNA sequence predicts a
      precursor protein of 270 amino acids, which shares significant homology with the
      amino acid sequence of another chlorophyll-binding protein; the chlorophyll a/b
      binding (Cab) protein of the photosystem II light-harvesting complex (LHCII).
      There are two extensive regions of homology (at least 45 residues each) which
      have approximately 50% amino acid sequence identity. These regions coincide with
      two of the proposed membrane-spanning alpha helices in the Cab proteins of the
      LHCII and probably include conserved chlorophyll-binding sites. The LHCI-15 cDNA
      hybridizes to at least 7 genomic EcoRI DNA fragments, which are very closely
      related at the nucleotide sequence level. 

PMID- 24277499
TI  - DNA repair precedes replicative synthesis during early germination in maize.
AB  - DNA synthesis was studied during germination by following the rate of
      incorporation of radioactive thymidine into high molecular weight DNA. A peak of
      DNA synthesis was observed between the 8th and the 12th hour, i.e. before the
      beginning of the semi-conservative replication of genomic DNA, accompanied by an
      increase in the DNA content of the embryo. By the use of nucleoid sedimentation
      and nick-translation it was shown that, during the first hours of germination,
      extensive repair occurs of the DNA single-strand breaks present in the dry
      embryo. As a result, the DNA of the 16-h-germinated embryo acquires the
      conformation typical of that of the root meristemic cells active in transcription
      and replication.In addition we have shown that cytoplasmic organelle (most
      probably mitochondrial) DNA synthesis is very active during the prereplicative
      state which confirms earlier microscopic data on mitochondrial biogenesis during
      early germination. 

PMID- 24277500
TI  - Auxin-induced mRNA species in tobacco cell cultures.
AB  - Using a 2,4-dichlorophenoxyacetic acid (2,4-D)-dependent tobacco cell-suspension
      culture we analyzed early hormone-induced molecular events preceding cell
      division. By differential screening of a cDNA library to mRNAs derived from
      hormone-starved cells treated with 2,4-D for 4 h, seven non-cross hybridizing
      cDNA clones to 2,4-D-induced mRNAs were obtained. Accumulation of these mRNAs
      started as early as 15-30 min or less after 2,4-D application. The lowest 2,4-D
      concentration necessary to induce the mRNAs varied between less than 2.2 * 10(-8)
      M and 2.2 * 10(-6) M, one mRNA being induced to nearly maximal values at 2.2 *
      10(-6) M. Generally, 2,4-D was the most active compound to induce mRNA
      accumulation, followed by naphthalene-1-acetic acid (NAA). The level of 4 mRNAs
      increased independently from protein synthesis. Run-off transcription studies
      showed that the accumulation of some mRNAs was at least partly due to enhanced
      transcription rates. In different organs of the tobacco plant, the levels of the
      mRNAs were about as low as in hormone-starved cells. A similar low level of the
      2,4-D-induced mRNAs was observed in cells growing in mid-log phase on 2,4-D
      containing medium. Only quiescent cells that were triggered to undergo cell
      division, accumulate these mRNAs transiently. 

PMID- 24277501
TI  - The chalcone synthase multigene family of Petunia hybrida (V30): sequence
      homology, chromosomal localization and evolutionary aspects.
AB  - Chalcone synthase (CHS) genes in Petunia hybrida comprise a multigene family
      containing at least 7 complete members in the strain Violet 30 (V30). Based on a
      high sequence homology in both coding and non-coding sequence, a number of CHS
      genes can be placed into two subfamilies. By restriction fragment length
      polymorphism (RFLP) analysis it was shown that both chromosomes II and V carry
      one of these subfamilies, in addition to the other CHS genes identified so far.
      Members of a subfamily were found to be closely linked genetically. Analysis of
      the Petunia species that contributed to the hybrid nature of P. hybrida (P.
      axillaris, P. parodii, P. inflata and P. violacea) shows that none of the CHS
      gene clusters is specific for either one of the parents and therefore did not
      arise as a consequence of the hybridization. The number of CHS genes within a
      subfamily varies considerably among these Petunia species. From this we infer
      that the CHS subfamilies arose from very recent gene duplications. 

PMID- 24277502
TI  - The isolation, characterization and sequence of two divergent beta-tubulin genes
      from soybean (Glycine max L.).
AB  - Two divergent beta-tubulin genes (designated Sbeta-1 and Sbeta-2) were isolated
      by screening a soybean genomic library with a Chlamydomonas reinhardtii beta
      tubulin cDNA probe. Restriction fragment analysis of the clones recovered, and of
      soybean genomic DNA, indicated that these represent two unique classes of
      structurally different beta-tubulin genes in the soybean genome. However, it is
      possible that unidentified members of these classes or additional highly
      divergent classes of beta-tubulin genes (thus far undetected) exist in the
      soybean genome. The Sbeta-1 and Sbeta-2 genomic clones were sequenced, revealing
      that both are potentially functional genes which would encode beta-tubulins of
      445 and 449 amino acids, respectively. A comparison of their derived amino acid
      sequences with beta-tubulins from several organisms showed that they are most
      homologous to Chlamydomonas beta-tubulin (85-87%), with lesser degrees of
      homology to beta-tubulins of vertebrate species (79-83%), Trypanosoma brucei (80
      81%) and Saccharomyces cerevisiae (66-68%). The amino acid sequences of Sbeta-1
      and Sbeta-2 are as divergent from each other as they are from the Chlamydomonas
      beta-tubulin. The amino acids at the diverged positions in Sbeta-2 are nearly all
      conservative substitutions while in Sbeta-1, 18 of the 69 substitutions were non
      conservative. Both soybean beta-tubulin genes contain two introns in exactly the
      same positions. The first soybean intron is located in the same position as the
      third intron of the Chlamydomonas beta-tubulin genes. Codon usage in the two
      soybean beta-tubulins is remarkably similar (D (2)=0.87), but differs from codon
      usage in other soybean genes. 

PMID- 24277503
TI  - Definitive endoderm differentiation of human-induced pluripotent stem cells using
      signaling molecules and IDE1 in three-dimensional polymer scaffold.
AB  - Human-induced pluripotent stem cells (hiPSCs) are considered to be potentially
      able to differentiate into all human cell lineages and thus hold promise as an
      unlimited source for cell replacement therapies in clinical applications.
      Definitive endoderm (DE) formation is the first and crucial step in the
      development of visceral organs such as liver, lung, pancreas and so forth.
      Therefore, efficient generation of DE cells ensures the efficient generation of
      eventual target cells used in cell therapy. In the present study, Matrigel-coated
      poly(lactic acid)/gelatin (PLA/gelatin) nanofibrous scaffolds were utilized to
      investigate the proliferation and differentiation of hiPSCs into DE cells.
      Analyses of DE-specific markers including Sox17, FoxA2, and Gooscoid (Gsc) genes
      revealed higher levels of mRNA and protein expression in the differentiated
      hiPSCs cells cultured on PLA/gelatin scaffolds than cells differentiated in two
      dimensional (2D) culture. Our results showed that three-dimensional (3D) cultures
      could significantly promote DE differentiation in comparison with 2D culture.
      Also using small molecules such as inducer of definitive endoderm 1 (IDE1) and
      signaling molecules such as Activin A and Wnt3a could enhance the DE
      differentiation of hiPSCs with Activin A/Wnt3a being significantly more potent in
      both 2D and 3D cultures compared to IDE1. The results of this study may have
      impact in tissue engineering and cell replacement therapy of visceral organs
      related diseases.

PMID- 24277504
TI  - Inflammation in adipose tissue and fatty acid anabolism: when enough is enough!
AB  - Recent findings in adipose tissue (AT) have uncovered negative interactions among
      obesity, lipogenesis, and fatty acid (FA) storage, perhaps in response to the
      increased production of proinflammatory cytokines and transcription factors.
      Emerging evidence highlights that local hypoxia, generation of reactive oxygen
      and nitrogen species, increased immune cells infiltration and activation,
      senescence, inflammation, energy consumption, and decreased lipogenesis in the AT
      are interrelated and may lead to impaired cytokine and hormonal secretion by
      adipocytes, and ectopic fat deposition in obesity that strengths the increased
      risk of suffering metabolic disorders in obese subjects. The information
      summarized in this review attempts to defend the interdependent relationship of
      these proofs of concept, supporting the idea that "inflamed" and "dysfunctional"
      AT are synonymous when referring to obesity. This may happen in severe obese
      subjects with a large and long-lasting fat excess, when fat depots have reached
      the point in which excessive fat storage, cell density, and diminished oxygen
      availability promote decreased lipo/adipogenesis and increased lipolysis and FA
      release. This response may be induced by an important inflammatory component that
      promotes angiogenesis and insulin resistance, but also by leptin and the increase
      of T3 in hyperplastic AT. 

PMID- 24277505
TI  - Femoro-acetabular impingement: what the general radiologist should know.
AB  - Femoro-acetabular impingement (FAI) is a common condition in young active
      subjects, which can lead to the development of early osteoarthritis if not
      correctly diagnosed. Imaging evaluation of FAI, mainly based on plain film and
      magnetic resonance evaluation, must be performed according to precise guidelines
      and is fundamental for reaching a final diagnosis. The purpose of this paper is
      to provide a clinical and radiological overview of FAI by describing the most
      common clinical tests, the imaging techniques used in the diagnosis, and the main
      radiological signs that may be encountered. 

PMID- 24277506
TI  - Acceptance of noninvasive computed tomography coronary angiography: for a patient
      friendly medicine.
AB  - PURPOSE: This study was done to evaluate the psychological state and anxiety of
      patients undergoing computed tomography coronary angiography (CTCA), and assess
      their acceptance and satisfaction compared to invasive conventional coronary
      angiography (CCA). MATERIALS AND METHODS: A total of 442 consecutive patients
      (282 male; mean age 57.7 +/- 9.5 years) who underwent CTCA for suspected or known
      coronary artery disease were evaluated with the Endler Multimodality Anxiety
      Scales (EMAS) before and after the scan, and a questionnaire administered after
      the scan. Among the 442 patients, 181 had a history of CCA. Two radiologists
      assessed the image quality of CTCA. RESULTS: Anxiety was more intense prior to
      the scan (EMAS score 51.7 vs. 46.7, p < 0.01) and in patients with a history of
      CCA (EMAS score 55.5 vs. 49.1, p < 0.01). Women presented more intense anxiety
      (EMAS score 59.5 vs. 47.3, p < 0.01), higher mean heart rate (63.5 +/- 7.6 vs.
      60.7 +/- 7.3 beats per minute, p < 0.01) and a lower image quality than men (p <
      0.0001). CTCA proved to be more acceptable than CCA because of accurate
      preparation, lower concern prior to the examination, negligible pain, higher
      comfort, and greater overall satisfaction (p < 0.0001). CONCLUSIONS: Computed
      tomography coronary angiography is a patient-friendly imaging method because of
      the minimal perceived discomfort. Anxiety may affect CTCA image quality in women.

PMID- 24277507
TI  - Therapeutic impact of (18)F-FDG PET/CT in recurrent differentiated thyroid
      carcinoma.
AB  - PURPOSE: (18)F-fluorodeoxyglucose-positron emission tomography/computed
      tomography (PET/CT) has proved effective in detecting recurrent or metastatic
      differentiated thyroid carcinoma (DTC) in the follow-up of operated DTC patients
      with high thyroglobulin (Tg) levels and negative findings on radioiodine whole
      body scan. The aim of this retrospective study was to assess the impact of PET/CT
      on the planning of appropriate treatment for known recurrent disease in operated
      DTC patients. MATERIALS AND METHODS: The study concerned 44 consecutive DTC
      patients (36 papillary, 8 follicular), who underwent total thyroidectomy and
      thyroid remnant ablation with (131)I and PET/CT. All patients had proven or
      strongly suspected recurrent disease judging from neck ultrasound (US) and fine
      needle aspiration cytology, and detectable basal Tg levels. RESULTS: PET/CT
      findings were positive in 25/44 patients (56.81 %) and negative in 19. A positive
      PET/CT result predicted resectable tumour recurrences in 19/25 patients, but also
      detected additional tumour sites that prompted changes to the treatment plan in
      6/25 patients (24 %). A negative PET/CT result led to clinical monitoring for
      11/19 patients (57.89 %). CONCLUSIONS: PET/CT can help select patients, who might
      benefit from a tailored therapy by improving the detection of local recurrences
      not apparent on neck US or metastases.

PMID- 24277508
TI  - Solid pseudopapillary tumour of the pancreas: distinct patterns of computed
      tomography manifestation for male versus female patients.
AB  - PURPOSE: The purpose of this study was to retrospectively assess the features of
      computed tomography (CT) images and clinical characteristics of male patients
      with solid pseudopapillary tumours (SPTs) and compare them with those of female
      patients. MATERIALS AND METHODS: Computed tomography images and clinical data of
      102 patients with pathologically proven SPTs were reviewed. Details of the
      location, diameter, shape, encapsulation, calcification, internal composition, CT
      attenuation, and enhancement pattern of tumours were noted. Statistical analysis
      was performed using the chi (2) and t tests. RESULTS: Data from 16 males and 86
      females were collected. Males were significantly older than females (38.5 years
      vs. 28.7 years; P = 0.004). Except for mean age, no significant statistical
      difference was observed between the clinical factors of SPTs in males and
      females. The mean tumour size in males was significantly smaller than that in
      females (5.3 vs. 7.6 cm; P = 0.037). Solid tumours were more common in males
      (8/16; 50 %) than in females (5/86; 5.8 %; P < 0.001). CONCLUSION: The imaging
      features of SPTs of males are different from those of females. In males, the
      finding of small, prominently solid tumours showing enhancement patterns typical
      of SPTs may suggest a diagnosis of SPT.

PMID- 24277509
TI  - Neoadjuvant treatment of soft tissue sarcoma.
AB  - PURPOSE: The aim of this study was to evaluate disease-free survival (DFS),
      overall survival and toxicity of patients who underwent preoperative therapy for
      soft tissue sarcoma. MATERIALS AND METHODS: The data of 38 consecutive patients
      affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %)
      patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with
      neoadjuvant chemo-radiation therapy. Surgery was performed within 4-6 weeks after
      the completion of neoadjuvant treatment. RESULTS: Median follow-up was 4.9 years
      (range 1-13.7 years). All patients received preoperative external beam
      radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy
      treatment associated with radiotherapy. After neoadjuvant treatment, the majority
      of patients underwent wide excision (32 out of 38) and five patients had marginal
      surgery; only one patient underwent amputation. Local recurrence was observed in
      only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic
      relapse. At the time of our analysis 13 patients (34.2 %) had died due to
      metastatic spread of the disease. In our series, DFS in relation to distant
      metastases (DM) showed a significant result for lower limb involvement (p =
      0.038) and marginal excision (p = 0.024), both predictors of a worse DFS,
      histology was statistically significant although it was not possible to evaluate
      the risk for specific histology due to the small number of events in the
      different subtypes. CONCLUSIONS: The results obtained from our study are
      encouraging with regard to the feasibility and efficacy of preoperative RT in the
      treatment of soft tissue sarcoma in view of the results obtained in terms of
      local control, limb sparing and safety.

PMID- 24277510
TI  - Comparative evaluation of percutaneous laser and radiofrequency ablation in
      patients with HCC smaller than 4 cm.
AB  - OBJECTIVE: This study was done to compare percutaneous laser ablation (PLA) and
      radiofrequency thermoablation (RFA) for the treatment of hepatocellular carcinoma
      (HCC) <= 4 cm, in patients with liver cirrhosis. MATERIALS AND METHODS: Thirty
      patients with single HCC <= 4 cm in diameter were randomly assigned to one of two
      treatments: 15 patients were treated with PLA, using a multifibre system
      connected to a neodymium yttrium-aluminium-garnet laser source; 15 patients were
      treated with RFA, using an expandable needle electrode. Patients were followed up
      for up to 12 months. RESULTS: A complete response was obtained in 87 % lesions
      treated with PLA and in 93 % lesions treated with RFA (p = ns). The overall local
      recurrence-free survival rates at 3, 6 and 12 months were comparable. However, a
      higher rate of recurrence was observed in the PLA group for lesions >= 21 mm (p =
      0.0081). A postablation syndrome was documented in 13 patients (1 PLA; 12 RFA).
      Tumour necrosis factor-alpha was significantly higher in the RFA group (p <
      0.05). CONCLUSIONS: RFA is more effective in the treatment of HCC compared to PLA
      for lesions >= 21 mm. However, PLA should be considered a viable treatment option
      for HCC <= 20 mm, in view of the lower incidence of complications.

PMID- 24277511
TI  - PET-CT in oncological patients: analysis of informal care costs in cost-benefit
      assessment.
AB  - PURPOSE: The authors analysed the impact of nonmedical costs (travel, loss of
      productivity) in an economic analysis of PET-CT (positron-emission tomography
      computed tomography) performed with standard contrast-enhanced CT protocols
      (CECT). MATERIALS AND METHODS: From October to November 2009, a total of 100
      patients referred to our institute were administered a questionnaire to evaluate
      the nonmedical costs of PET-CT. In addition, the medical costs (equipment
      maintenance and depreciation, consumables and staff) related to PET-CT performed
      with CECT and PET-CT with low-dose nonenhanced CT and separate CECT were also
      estimated. RESULTS: The medical costs were 919.3 euro for PET-CT with separate
      CECT, and 801.3 euro for PET-CT with CECT. Therefore, savings of approximately
      13% are possible. Moreover, savings in nonmedical costs can be achieved by
      reducing the number of hospital visits required by patients undergoing diagnostic
      imaging. CONCLUSIONS: Nonmedical costs heavily affect patients' finances as well
      as having an indirect impact on national health expenditure. Our results show
      that PET-CT performed with standard dose CECT in a single session provides
      benefits in terms of both medical and nonmedical costs.

PMID- 24277512
TI  - Liposome-mediated introduction of the chloramphenicol acetyl transferase (CAT)
      gene and its expression in tobacco protoplasts.
AB  - The expression plasmid vector pUC8CaMVCAT, containing the chloramphenicol acetyl
      transferase (CAT) gene, was encapsulated in large unilamellar vesicles (LUV) and
      introduced into tobacco protoplasts derived from either cell suspension culture
      or leaf mesophyll. Treatment with liposomes took place in a buffer containing
      either NaCl or CaCl2, but no polyethylene glycol. The presence of polylysine in
      the incubation buffer increased the adsorption of liposomes to protoplasts but
      decreased the efficiency of CAT gene expression.The expression of the introduced
      CAT gene could be monitored for at least seven days, following the treatment
      (about 25% acetylation at day 3 as well as at day 7). Plasmid DNA sequences could
      be detected, apparently unmodified, for at least nine days in the plant cells,
      though unintegrated in the host genome. 

PMID- 24277513
TI  - Molecular analysis of actinidin, the cysteine proteinase of Actinidia chinensis.
AB  - We have isolated and sequenced two very similar cDNA clones of 1145 and 809 bp
      length, from a fruit-specific library of Actinidia chinensis, the larger encoding
      all 220 amino acids of actinidin, showing 91% homology to the published amino
      acid sequence. Both cDNAs code for an additional 25 amino acids following the
      mature carboxy terminus of actinidin. The larger clone has coding potential for
      57 residues of an amino-terminal extension with considerable homology to amino
      terminal sequences of other cysteine proteinases. From size determination of both
      mRNA (1.4 kb) and immunoprecipitated in vitro translation product (39 kDa) it was
      estimated that actinidin is synthesised as a precursor approximately 15 kDa
      larger than the mature protein. Both proteolytic cleavage sites are located on
      the surface of the molecule as illustrated by the hydropathy profile of the
      deduced amino acid sequence. Features of the prosegment primary sequence are
      considered with regard to a possible mechanism of inactivation of the proteinase,
      by analogy with other proteolytic zymogens. The presence of three potential
      glycosylation sites, one within the carboxy-terminal and two in the amino
      terminal extension, are consistent with subcellular location of the enzyme within
      membrane-bound organelles. Results from a Southern blot suggest that actinidin is
      encoded by a multigene family of up to ten members. Actinidin gene expression,
      both at the level of mRNA and protein, is largely restricted to the fruit of the
      plant, where the level of actinidin mRNA accumulates early during development. 

PMID- 24277514
TI  - Tissue-specific expression of a pea legumin gene in seeds of Nicotiana
      plumbaginifolia.
AB  - A 3.4-kilobase genomic DNA fragment from Pisum sativum L. containing the LegA
      gene, which encodes a major legumin storage protein, was transferred to Nicotiana
      plumbaginifolia using an Agrobacterium tumefaciens strain containing the Bin 19
      binary vector system. Northern hybridisation analysis of legA-transformed plants
      demonstrated that legumin-specific RNA was present in developing seeds but not in
      developing leaves. Legumin protein was immunologically detected in the mature
      seeds of legA-transformed plants, and was present as the correct-size protein
      composed of disulphide-bonded polypeptides. It is concluded that the transferred
      pea genomic fragment contains all the information necessary for seed-specific
      expression of the legA gene, and for correct processing of the primary transcript
      and the precursor legumin protein. 

PMID- 24277515
TI  - cDNAs of two non-allelic sucrose synthase genes in maize: cloning, expression,
      characterization and molecular mapping of the sucrose synthase-2 gene.
AB  - cDNA clones of the two non-allelic sucrose synthase (Ss) genes, Ss2 and Sh, have
      been isolated from lambdagt11 expression libraries derived from immature kernel
      poly(A)(+) RNA of sh-deletion and Sh/Sh genotypes of maize respectively.
      Recombinant clones containing the longest Ss2 and Sh cDNA inserts, each of
      approximately 2.5 kb size, were characterized and comparatively analyzed.
      Although the Sh cDNA insert expresses as a sucrose synthase-1 (SS1) beta
      galactosidase fusion protein (~ 200 kD) in lambda lysogens, the Ss2 cDNA failed
      to form such a chimeric protein and instead showed a ~ 70 kD SS2 polypeptide. The
      Ss2 and Sh cDNAs as hybridization probes on RNA blots of immature kernels
      detected a larger Ss2 transcript (~ 2900 b) than the Sh transcript (~ 2750 b).
      Because SS1 and SS2 protein subunits are known to be of identical size, the
      significance of difference in transcript size is not apparent. A comparative
      restriction enzyme mapping of the two cDNA clones and a genomic Ss2 clone show
      sequence diversity over the entire lengths of Ss2 and Sh clones. Interestingly,
      restriction endonuclease sites around the 3' ends are more conserved than the 5'
      ends of these two genes. Genetic data indicate that the Ss2 locus is on
      chromosome 9 and molecular mapping using the Ss2 cDNA clone on recombinant inbred
      lines and B-A translocations stocks suggest that Ss2 is about 20 map units away
      from the Wx locus on 9L. 

PMID- 24277516
TI  - Agrobacterium-mediated inoculation of plants with tomato golden mosaic virus
      DNAs.
AB  - We have adapted the "agroinfection" procedure of Grimsley and co-workers [4,5] to
      develop a simple, efficient, reproducible infectivity assay for the insect
      transmitted, split-genome geminivirus, tomato golden mosaic virus (TGMV).
      Agrobacterium T-DNA vectors provide efficient delivery of both components of TGMV
      when used in mixed inoculation of wild-type host plants. A greater increase in
      infection efficiency can be obtained by Agrobacterium delivery of the TGMV A
      component to "permissive" transgenic plants. These "permissive" plants contain
      multiple tandem copies of the B component integrated into the host genome. An
      inoculum containing as few as 2000 Agrobacterium cells can produce 100% infection
      under these conditions. Further, our results show that there is a marked effect
      of the configuration of the TGMV A components within the T-DNA vector on time of
      symptom development. We have also found that transgenic plants carrying tandem
      copies of the A component do not complement the B component. Possible mechanisms
      to explain these results and the potential use of this system to further study
      the functions of the geminivirus components in infection are discussed. 

PMID- 24277517
TI  - Control of gene expression during induction of cultured peanut cells: mRNA
      levels, protein synthesis and enzyme activity of stilbene synthase.
AB  - Stilbene synthase is an inducible enzyme occurring in a small number of plants.
      The enzyme is amenable to analysis and biochemical studies only after the cells
      are subjected to induction. Cell suspension cultures of peanut react very
      selectively if elicited with biotic inducers. Just as intact peanut plants
      produce stilbene phytoalexins when attacked by fungi so also do sterile cultured
      cells when treated with sterilized insoluble fungal cell walls. Both systems
      react by synthesizing stilbene synthase. The time courses of increase in enzyme
      activity, protein synthesis and mRNA activity were studied, and their relation to
      other activities of the cells was elaborated. The results show that, after
      applying the fungal elicitor, the system responds very quickly and selectively:
      within 2 hours the synthesis rate of stilbene synthase protein is increased more
      than 30-fold, the increase being detectable 40 min after induction. The first
      increase in translatable mRNA for stilbene synthase can be seen 20 min after
      application of the stimulus. Stilbene synthase synthesized in vivo was compared
      to stilbene synthase prepared by translation in vitro. There was no difference in
      size, and limited proteolysis did not indicate significant differences in the
      peptide structure of the primary translation product and the active enzyme. 

PMID- 24277518
TI  - Chlorella chloroplast DNA sequence containing a gene for the large subunit of
      ribulose-1,5-bisphosphate carboxylase/oxygenase and a part of a possible gene for
      the beta' subunit of RNA polymerase.
AB  - The sequence of a 2782 bp fragment of the chloroplast genome of Chlorella
      ellipsoidea has been determined. The region includes the entire gene (rbcL) for
      the large subunit (LS) of ribulose-1,5-bisphosphate carboxylase/oxygenase and a
      sequence (rpoC-like) similar to part of the gene for the subunit of E. coli RNA
      polymerase which is oriented in same direction as rbcL. The arrangement is rpoC
      like - 446 bp - rbcL. The rbcL gene codes for a polypeptide of 475 amino acids
      whose sequence shows 88% homology with those of tobacco and spinach, 94% homology
      with that of Chlamydomonas, and 85% homology with that of Anacystis. The putative
      rbcL promoter sequence has homology with E. coli promoter sequences and its
      putative terminator sequence is capable of forming a stem-and-loop structure. 

PMID- 24277519
TI  - Genes for tRNA(Asp), tRNA (Pro), tRNA (Tyr) and two tRNAs (Ser) in wheat
      mitochondrial DNA.
AB  - We have begun a systematic search for potential tRNA genes in wheat mtDNA, and
      present here the sequences of regions of the wheat mitochondrial genome that
      encode genes for tRNA(Asp) (anticodon GUC), tRNA(Pro) (UGG), tRNA(Tyr) (GUA), and
      two tRNAs(Ser) (UGA and GCU). These genes are all solitary, not immediately
      adjacent to other tRNA or known protein coding genes. Each of the encoded tRNAs
      can assume a secondary structure that conforms to the standard cloverleaf model,
      and that displays none of the structural aberrations peculiar to some of the
      corresponding mitochondrial tRNAs from other eukaryotes. The wheat mitochondrial
      tRNA sequences are, on average, substantially more similar to their eubacterial
      and chloroplast counterparts than to their homologues in fungal and animal
      mitochondria. However, an analysis of regions ~ 150 nucleotides upstream and ~
      100 nucleotides downstream of the tRNA coding regions has revealed no obvious
      conserved sequences that resemble the promoter and terminator motifs that
      regulate the expression of eubacterial and some chloroplast tRNA genes. When
      restriction digests of wheat mtDNA are probed with (32)P-labelled wheat
      mitochondrial tRNAs, <20 hybridizing bands are detected, whether enzymes with 4
      bp or 6 bp recognition sites are used. This suggests that the wheat mitochondrial
      genome, despite its large size, may carry a relatively small number of tRNA
      genes. 

PMID- 24277520
TI  - Properties of an isolated transcription stimulating sequence derived from the
      cauliflower mosaic virus 35S promoter.
AB  - As a highly active plant viral promoter that is able to function in a wide
      variety of cell types, the cauliflower mosaic virus (CaMV) 35S promoter has the
      potential for harboring a plant enhancer element. We tested this possibility and
      demonstrated that a 338 base pair fragment isolated from the region upstream of
      the 35S TATA box can increase the expression of a low-activity heterologous
      promoter up to the level observed for the intact 35S promoter. This fragment is
      fully active in both orientations when placed 150 base pairs upstream of the
      transcription start site. However, the activity of this fragment is sensitive to
      location, demonstrating a reduction in activity and loss of orientation
      independent function when the distance from the transcription start site is
      increased. By assaying fragments of different sizes, we have also characterized
      regions that are functional in directing the stimulation of the heterologous
      promoter. 

PMID- 24277521
TI  - An embryogenic cell line of maize from A188 (Minnesota) contains Mu1-like
      elements.
AB  - The maize inbred line A188 is popularly used for the production of embryogenic
      cell lines. A188, maintained at the University of Minnesota, was found upon
      molecular analysis to contain 2 to 4 copies of a DNA sequence very similar in
      structure to transposable Mu1 elements, which have been implicated in Robertson's
      Mutator system. These Mu1-like elements are in the same chromosomal locations in
      sibling plants and in A188 cell cultures derived from them. This suggests that
      the elements are in an inactive state and do not undergo transposition. However,
      we have observed that they are not modified at the target sites for certain
      restriction endonucleases. Possible causes for the apparent lack of transposition
      of these Mu1-like elements in these A188 lines are discussed. Inasmuch as the
      elements do not transpose, they must be maintained in this line as homozygous
      Mendelian elements by self-pollination. 

PMID- 24277522
TI  - Creation of novel nitrogen-fixing actinomycetes by protoplast fusion of Frankia
      with streptomyces.
AB  - Protoplast fusion was used for the creation of a novel actinomycete capable of
      fixing atmospheric nitrogen. Protoplasts of Streptomyces griseofuscus, a fast
      growing actinomycete, and Frankia, a slow-growing actinomycete which fixes
      atmospheric nitrogen in culture and in symbiotic association with alders, were
      allowed to fuse and regenerate on media without supplied nitrogen. Colonies which
      regenerated acquired the fast-growing characteristic of Streptomyces and the
      ability to grow on nitrogen-deficient media from Frankia. These colonies
      resembled Streptomyces in their morphology and fixed atmospheric nitrogen in
      culture. They contained both the parent Streptomyces DNA sequences and the
      Frankia DNA sequences homologous to nif structural genes HDK of K. pneumoniae. In
      addition to in vitro nitrogen-fixing capacity, one out of 20 colonies also formed
      nitrogen-fixing root nodules on Alnus rubra, the host plant for the Frankia
      strain. Examination of the root nodules induced by the hybrids showed only the
      presence of hyphae-like structures. The typical vesicle-like structures present
      in Frankia were absent. 

PMID- 24277523
TI  - Role and mechanism of microglial activation in iron-induced selective and
      progressive dopaminergic neurodegeneration.
AB  - Parkinson's disease (PD) patients have excessive iron depositions in substantia
      nigra (SN). Neuroinflammation characterized by microglial activation is pivotal
      for dopaminergic neurodegeneration in PD. However, the role and mechanism of
      microglial activation in iron-induced dopaminergic neurodegeneration in SN remain
      unclear yet. This study aimed to investigate the role and mechanism of microglial
      beta-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in
      iron-induced selective and progressive dopaminergic neurodegeneration. Multiple
      primary midbrain cultures from rat, NOX2+/+ and NOX2-/- mice were used.
      Dopaminergic neurons, total neurons, and microglia were visualized by
      immunostainings. Cell viability was measured by MTT assay. Superoxide (O2.-) and
      intracellular reactive oxygen species (iROS) were determined by measuring SOD
      inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and
      protein were detected by real-time PCR and Western blot. Iron induces selective
      and progressive dopaminergic neurotoxicity in rat neuron-microglia-astroglia
      cultures and microglial activation potentiates the neurotoxicity. Activated
      microglia produce a magnitude of O2.- and iROS, and display morphological
      alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited
      dopaminergic neurotoxicity through decreasing microglial O2.- generation, and
      NOX2-/- mice are resistant to the neurotoxicity by reducing microglial O2.-
      production, indicating that iron-elicited dopaminergic neurotoxicity is dependent
      of NOX2, a O2.--generating enzyme. NOX2 activation is indicated by the increased
      mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2
      activation include PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 as their mRNA and
      protein levels are enhanced by NOX2 activation. Iron causes selective and
      progressive dopaminergic neurodegeneration, and microglial NOX2 activation
      potentiates the neurotoxicity. PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 are the
      potential molecules relevant to microglial NOX2 activation.

PMID- 24277524
TI  - Mutations of the Huntington's disease protein impact on the ATM-dependent
      signaling and repair pathways of the radiation-induced DNA double-strand breaks:
      corrective effect of statins and bisphosphonates.
AB  - Huntington's disease (HD) is a neurodegenerative syndrome caused by mutations of
      the IT15 gene encoding for the huntingtin protein. Some research groups have
      previously shown that HD is associated with cellular radiosensitivity in
      quiescent cells. However, there is still no mechanistic model explaining such
      specific clinical feature. Here, we examined the ATM-dependent signaling and
      repair pathways of the DNA double-strand breaks (DSB), the key damage induced by
      ionizing radiation, in human HD skin fibroblasts. Early after irradiation,
      quiescent HD fibroblasts showed an abnormally low rate of recognized DSB managed
      by non-homologous end-joining reflected by a low yield of nuclear foci formed by
      phosphorylated H2AX histones and by 53BP1 protein. Furthermore, HD cells elicited
      a significant but moderate yield of unrepaired DSB 24 h after irradiation.
      Irradiated HD cells also presented a delayed nucleo-shuttling of phosphorylated
      forms of the ATM kinase, potentially due to a specific binding of ATM to mutated
      huntingtin in the cytoplasm. Our results suggest that HD belongs to the group of
      syndromes associated with a low but significant defect of DSB signaling and
      repair defect associated with radiosensitivity. A combination of biphosphonates
      and statins complements these impairments by facilitating the nucleo-shuttling of
      ATM, increasing the yield of recognized and repaired DSB. 

PMID- 24277526
TI  - Graphene/graphene-tube nanocomposites templated from cage-containing metal
      organic frameworks for oxygen reduction in Li-O2 batteries.
AB  - Nitrogen-doped graphene/graphene-tube nanocomposites are prepared by a
      hightemperature approach using a newly designed cage-containing metal-organic
      framework (MOF) to template nitrogen/carbon (dicyandiamide) and iron precursors.
      The resulting N-Fe-MOF catalysts universally exhibit high oxygen-reduction
      activity in acidic, alkaline, and non-aqueous electrolytes and superior cathode
      performance in Li-O2 batteries. 

PMID- 24277527
TI  - Primary prevention: The search for a new paradigm.

PMID- 24277528
TI  - The argument for primary prevention.

PMID- 24277530
TI  - Reaction.

PMID- 24277529
TI  - The argument against primary prevention.

PMID- 24277525
TI  - Chronic nicotine treatment reverses hypothyroidism-induced impairment of L-LTP
      induction phase: critical role of CREB.
AB  - We have previously shown that adult onset hypothyroidism impairs late-phase long
      term potentiation (L-LTP) and reduces basal protein levels of cyclic-AMP response
      element binding protein (CREB), mutagen-activated protein kinase (MAPKp42/44),
      and calcium calmodulin kinase IV (CaMKIV) in area Cornu Ammonis 1 (CA1) of the
      hippocampus. These changes were reversed by chronic nicotine treatment. In the
      present study, levels of signaling molecules important for L-LTP were determined
      in CA1 area of the hippocampus during the induction phase. Standard multiple high
      frequency stimulation (MHFS) was used to evoke L-LTP in the CA1 area of the
      hippocampus of hypothyroid, nicotine-treated hypothyroid, nicotine, and sham
      control anaesthetized adult rats. Chronic nicotine treatment reversed
      hypothyroidism-induced impairment of L-LTP at the induction phase. Five minutes
      after MHFS, Western blotting showed an increase in the levels of P-CREB, and P
      MAPKp42/44 in sham-operated control, nicotine, and nicotine-treated hypothyroid
      animals, but not in hypothyroid animals. The protein levels of total CREB, total
      MAPK p42/44, BDNF, and CaMKIV were not altered in all groups 5 min after MHFS.
      Therefore, normalized phosphorylation of essential kinases such as P-CREB and P
      MAPK p42/44 in the CA1 area of nicotine-treated hypothyroid animals plays a
      crucial role in nicotine-induced rescue of L-LTP induction during hypothyroidism.

PMID- 24277531
TI  - Reaction.

PMID- 24277532
TI  - Response to drs. Lamb and zusman.

PMID- 24277533
TI  - Response to drs. Albee and goldston.

PMID- 24277534
TI  - Debate on primary prevention: A paradigmatic response.

PMID- 24277535
TI  - Comments on the debate on primary prevention.

PMID- 24277537
TI  - Comments on the debate on primary prevention.

PMID- 24277536
TI  - Primary prevention: Rhetoric and metaphor.

PMID- 24277538
TI  - The debate on primary prevention: Toward a synthesis.
AB  - CONCLUSION: The primary prevention model presented above provides a "larger
      theoretical structure" capable of including both sides of the debate. It
      encourages primary prevention efforts yet builds in the careful assessment,
      planning, research, and evaluation needed to prevent excesses.Primary prevention
      is an experiment. It is thezeitgeist in mental health, and it will have its day.
      It is a powerful metaphor spurred by the dream of eradicating mental illness from
      society. Primary prevention may prove to be an important turning point in the
      history of mental health. Or it may end up on the junk heap of "progressive
      ideas" which were either unsound or unworkable. Either way, primary prevention is
      an idea whose time has finally come.

PMID- 24277539
TI  - Primary prevention: Looking for a middle ground.

PMID- 24277540
TI  - Primary prevention: Key issues and a competence perspective.
AB  - At a superficial level, one might characterize the primary prevention debate as
      centering on the question of whether primary prevention has been demonstrated to
      be an effective means of promoting mental health. This interpretation is
      supported by the clarity and strength of the confident generalizations of primary
      prevention proponents such as Dr. Albee ("We have a lot of evidence on the
      effectiveness of primary prevention ... it is available in the literature for all
      to read") and primary prevention critics such as Dr. Lamb ("... The major
      functional mental illnesses, as well as the frequently occurring diagnosable
      minor illnesses, remain untouched by efforts to strengthen mental health.").
      However, it seems clear that the disagreement is not primarily a matter of
      differences in data interpretation (although this is clearly a part of the
      problem). Rather, it seems to be mostly a function of differences at the level of
      basic assumptions about the nature of mental illness and the appropriate scope of
      activity for mental health professionals. 

PMID- 24277541
TI  - Is there a magic bullet for emotional illness?

PMID- 24277542
TI  - The concept of primary prevention: Creating new paradigms.
AB  - CONCLUSION: These five topics are different from many of the traditional
      professional activities of the mental health professions. They have been
      presented to clarify how the ambiguity of prevention work can be explored and how
      the substantive merit of primary prevention is increased. The complementary
      connections between the social sciences and the clinical professions is expected
      to be enhanced in working on these agendas. The challenge for preventive work is
      to bring together the insight of citizens and professionals, so that critical
      thinking and authentic needs for both can be integrated. Working on ideas such as
      these five can make it possible for professionals and citizens to develop new
      knowledge for new professional roles and new opportunities for citizen
      development. Here the professional and citizen become resources for each other,
      in contrast to the professional "treating" the "subject" or "patient." Prevention
      work means creating knowledge that is available directly for community
      development in contrast to individual treatment.

PMID- 24277543
TI  - Letter concerning primary prevention debate.

PMID- 24277544
TI  - A comment on the debate on primary prevention.

PMID- 24277545
TI  - Primary prevention: Should we support both practice and research?
AB  - The February 16, 1983 debate on Primary Prevention in which Albee and Goldston
      met Lamb and Zusman underlined a number of issues that are repeatedly discussed
      in such forums. In response to an invitation to comment on the debate by the
      Florida Mental Health Institute, I would like to focus on five of these issues. I
      should state at the outset that my comments are far from unbiased, as I am
      clearly an advocate for prevention intervention and prevention intervention
      research (Munoz & Kelly, 1975; Munoz, 1976; Christensen, Miller & Munoz, 1978;
      Munoz, Snowden & Kelly, 1979; Munoz, 1980; Munoz, 1982). In my discussion, I will
      try to: 1) identify some premises which were not sufficiently emphasized; 2) make
      such premises clear so that, hopefully, any further discussion is based on shared
      (or at least well-identified) starting points; and 3) add my perspectives in each
      of these areas. I will use examples dealing with affective disorders throughout
      my discussion, because they are among the most prevalent of disorders, and
      because they are present in various levels of severity. 

PMID- 24277546
TI  - Comments on the debate on primary prevention.

PMID- 24277548
TI  - New directions in the primary prevention of mental problems: Comment on a debate.

PMID- 24277547
TI  - Comments on debate.

PMID- 24277549
TI  - Addendum to debate statement.

PMID- 24277550
TI  - Last word.
AB  - Let me make clear to the reader that this modest debate has taken on a life of
      its own. When Herb Marlowe invited Dr. Lamb and me to debate on the subject of
      prevention I assumed, as I think Lamb did, that we would have a stimulating
      evening arguing good-naturedly in front of the live audience in Tampa, each of us
      with a support person: Dr. Goldston with me and Dr. Zusman with him. And that
      would be the end of it. I spoke from a few notes on the back of an envelope, and
      I assume that Dr. Lamb was similarly "prepared." But our words were captured by
      the objective permanence of electronics, and we were later asked to correct (not
      edit) the transcript to be sure it reflected what we said. Then still later a
      baker's dozen of experts was asked to comment on our remarks. (Understand, we
      were asked to agree to all of this-and we did.) But if we were to begin again, I
      think I would have prepared my remarks with somewhat more care, and perhaps Dr.
      Lamb would have too. Now our debate is to become archival, with publication in a
      professional journal. I have been given, as has Dr. Lamb, a chance to comment on
      the commentators' contributions. My response will be brief. 

PMID- 24277552
TI  - Parental criticism and young adolescent self-disclosure: A cross-cultural study.
AB  - Criticism by mothers and fathers, as well as young adolescents' perceptions of
      parental criticism and their self-disclosure to parents, was assessed for a
      sample of 80 families. Of these, 40 were resident in Australia (20 Anglo
      Australian and 20 Greek-Australian) and 40 were resident in Greece (20
      professional and 20 working-class). There were no differences between the groups
      in amount of criticism by parents nor in adolescents' perceptions of criticism.
      Greek- and Anglo-Australian adolescents disclosed significantly less to parents
      than did the Greek adolescents. For Greek-Australian adolescents there was an
      inverse relationship between self-disclosure on a number of topics and perceived
      levels of parental criticism. The results were interpreted in terms of cultural
      differences between the groups and adaptive behaviors of the Greek-Australian
      adolescents. 

PMID- 24277553
TI  - Gender differences in self-consistency: Evidence from an investigation of self
      concept structure.
AB  - This study investigates the relationship between two primary motivational
      components of the self-concept: self-esteem and self-consistency. Past research
      has shown that high self-esteem is associated with greater consistency. Developed
      from theories of the self-concept, a structural model relating these two
      constructs was posited such that (1) self-esteem is causally prior to self
      consistency, and (2) the effect of self-esteem is (at least partially) mediated
      by other components of the self-concept (self-consciousness, the tendency to
      fantasize, and the tendency to present a false front by hiding one's feelings).
      Utilizing a structural equation model with unobserved variables, an analysis of
      covariance structures was applied simultaneously but separately to data from a
      sample of boys and girls (ages 8-19). Results showed that the direct effect of
      self-esteem on self-consistency was stronger for boys than for girls. Further,
      the mediational properties of the other self-concept components also varied
      across gender. These differences are interpreted in light of theories of gender
      socialization. 

PMID- 24277551
TI  - Overview of early detection and treatment strategies for suicidal behavior in
      young people.
AB  - Suicidal behavior represents a major public health problem requiring the
      development and implementation of early detection and treatment strategies. This
      paper integrates a proposed model of risk factors with a multithreshold level of
      early detection in youth suicide. These riskfactor domains include psychiatric
      diagnosis, personality traits, psychosocial factors, life events and chronic
      medical illness, biological factors, and family history and genetics. The three
      levels of early detection are detection awareness, major problem awareness, and
      major psychiatric disorders. Each of these levels are described in detail with
      examples, followed by a review of intervention and treatment strategies for each
      level. Detection awareness requires a strong component of education and public
      health interventions. Major problem awareness requires a level of active
      intervention and treatment in dealing with behavior problems, personality issues,
      or specific life events. The final level deals not exclusively but primarily with
      the treatment of psychiatric disorders since it is proposed that treatment of
      specific psychiatric syndromes plays a major role in preventing suicide. The
      primary purpose of this paper is to outline a new approach to early detection and
      intervention for the prevention of youth suicide. 

PMID- 24277554
TI  - Separation-individuation and ego identity status in late adolescence: A two-year
      longitudinal study.
AB  - This study was undertaken to clarify developmental relationships between
      intrapsychic object relations structure and ego identity status during late
      adolescence; one purpose was to examine the possible predictive relationship
      between initial attachment style and later identity status. A total of 76
      subjects (41 females and 35 males) who had been given the Marcia Ego Identity
      Status Interview and the Hansburg Separation Anxiety Test (SAT) as first-year
      university students in 1984 were reassessed two years later. Fitted log linear
      models indicated strong links between attachment style and identity status in
      1986, and between identity status in 1984 and 1986; only an indirect connection
      existed between attachment style in 1984 and 1986 as measured by the SAT. When
      1984 and 1986 identity status were known, it was possible to predict 1986
      attachment style without knowing 1984 attachment style; 1984 attachment style
      alone was unable to predict later identity status accurately. 

PMID- 24277555
TI  - The relationship between ego identity status and Erikson's notions of
      institutionalized moratoria, value orientation stage, and ego dominance.
AB  - A number of concepts central to Erikson's theory of ego identity formation (J. E.
      Cote and C. Levine [1987], "A Formulation of Erikson's Theory of Ego Identity
      Formation," Development Review, 7(4): 273-325) are discussed in relation to
      Marcia's identity status paradigm in light of the fact that both assign a
      significant role to the notion of identity crisis. The results of an empirical
      investigation reveal that Erikson's notions of institutionalized moratoria, value
      orientation stages, and the ego-superego struggle for dominance of the
      personality are related to the identity status categories in a way that can be
      partially explained in terms of the degree to which an individual has experienced
      the identity crisis. Further explanations for the pattern of findings are offered
      in terms of Erikson's theory. These explanations clarify, to a degree, the nature
      of the identity statuses from a social psychological perspective. 

PMID- 24277556
TI  - A confirmatory factor analysis of a four-factor model of adolescent concerns.
AB  - Based on considerable previous research, a four-factor model of adolescent
      concerns was proposed. Data on concerns were collected from 439 adolescents
      together with demographic data. A hierarchy of concerns was established based on
      mean ratings, and sex and age differences were reported. The data were factor
      analyzed into four principal components and were tested for the goodness of fit
      to the proposed model using linear structural relationships (LISREL) techniques
      by the method of maximum likelihood. The data fit the model very well (goodness
      of fit index=.958). The implications of these findings for further research and
      theories of adolescent development are discussed generally. 

PMID- 24277557
TI  - Two-pore channels (TPCs): current controversies.
AB  - Much excitement surrounded the proposal that a family of endo-lysosomal channels,
      the two-pore channels (TPCs) were the long sought after targets of the Ca(2+) 
      mobilising messenger, nicotinic acid adenine dinucleotide phosphate (NAADP).
      However, the role of TPCs in NAADP signalling may be more complex than originally
      envisaged. First, NAADP may not bind directly to TPCs but via an accessory
      protein. Second, two papers recently challenged the notion that TPCs are NAADP
      regulated Ca(2+) channels by suggesting that they are highly selective Na(+)
      channels regulated by the lipid phosphatidylinositol 3,5-bisphosphate and by ATP.
      This paper aims critically to evaluate the evidence for TPCs as NAADP targets and
      to discuss how the new findings fit in with what we know about endo-lysosomal
      Ca(2+) stores. 

PMID- 24277558
TI  - [Lymphangioleiomyomatosis].
AB  - LAM is one of the rare lung diseases. Approximately 200-400 female patients are
      to be expected in Germany. Only rare reports exist describing a male LAM patient.
      LAM exists in two forms: a spontaneous mosaic mutation (S-LAM) and a germ line
      mutation resulting in a combination of pulmonary and systemic symptoms called
      tuberous sclerosis (TSC-LAM). Although the influence of estrogen is not yet
      entirely recognized, pregnancy and estrogen containing anticonception will worsen
      the course of the disease. Ten year prognosis of the disease is well over 80% but
      variability is large. Rapid progression exists.The clinical picture of S-LAM is
      dominated by pneumothorax, chylous pleural effusions, dyspnoea upon exertion.
      (HR) CT demonstrates the easily recognizable and characteristic cystic
      transformation of the parenchyma. The cellular sequels of the disease involve
      constant activation of the mTORC1 complex with protein synthesis, proliferation,
      enzymatic parenchymal transformation, improved cellular survival and metastasis
      into the lungs most likely from an extrapulmonary source. Following extensive
      research on the pathologic activation of the mTORC1 pathway, an initial way of
      halting progression has been found in using mTORC1 inhibitors (Sirolimus,
      Everolimus). Complimentary strategies are currently investigated in order to
      improve the therapeutic effect. These measures will improve LAM prognosis in the
      future. Therapy resistant LAM is a valid indication for lung transplantation.

PMID- 24277559
TI  - Beta-type calcium phosphates with and without magnesium: From hydrolysis of
      brushite powder to robocasting of periodic scaffolds.
AB  - Several approaches have attempted to replace extensive bone loss, but each of
      them has their limitation. Nowadays, additive manufacture techniques have shown
      great potential for bone engineering. The objective of this study was to
      synthesize beta tricalcium phosphate (beta-TCP), beta tricalcium phosphate
      substituted by magnesium (beta-TCMP), and biphasic calcium phosphate substituted
      by magnesium (BCMP) via hydrolysis and produce scaffolds for bone regeneration
      using robocasting technology. Calcium deficient apatites, with and without
      magnesium were obtained by hydrolysis, calcined and physico-chemically
      characterized. Colorimetric cell viability assay, calcium nodule formation, and
      the expression of alkaline phosphatase, osteocalcin, transforming growth factor
      beta-1 and collagen were assessed using a mouse osteoblastic cell line (MC3T3
      E1). Direct-write assembly of cylindrical periodic scaffolds was done via robotic
      deposition using beta-TCP, beta-TCMP, and BCMP colloidal inks. The sintered
      scaffolds were characterized by X-ray diffraction, Fourier-transform infrared
      spectroscopy, scanning electron microscopy, Archimede's method, and uniaxial
      compression test. According to the cell viability assay, the powders induced cell
      proliferation. Calcium nodule formation and bone markers activity suggested that
      the materials present potential value in bone tissue engineering. The scaffolds
      built by robocasting presented interconnected porous and exhibited mean
      compressive strength between 7.63 and 18.67 MPa, compatible with trabecular bone.

PMID- 24277560
TI  - Nucleotide sequence of psbC, the gene encoding the CP-43 chlorophyll a-binding
      protein of Photosystem II, in the cyanobacterium Synechocystis 6803.
AB  - The nucleotide sequence for the Photosystem II gene psbC has been determined for
      the cyanobacterium Synechocystis 6803. The gene overlaps the last 50 bases of the
      psbD gene, and both genes are transcribed in the same direction, but read in
      different frames. This arrangement is identical to that found in all chloroplast
      genomes for which psbC has been sequenced. The Synechocystis nucleotide sequence
      is 70% homologous to the tobacco gene and the predicted amino acid sequence shows
      85% homology. A possible alternative translation start site for psbC has been
      conserved between seven plant sequences and the cyanobacterial sequence. The
      hydropathy plot for the cyanobacterial protein is very similar to plots
      determined for six plant species. Pairs of histidines that may play a role in
      binding chlorophyll are conserved between the cyanobacterial and plant amino acid
      sequences. 

PMID- 24277561
TI  - Transcription of the wheat chloroplast gene that encodes the 32 kd polypeptide.
AB  - We have mapped and cloned the wheat chloroplast gene (psbA) that encodes the 32
      kd polypeptide of Photosystem II. The psbA gene is located in the large single
      copy region adjacent to one inverted repeat and is transcribed toward the latter.
      The sequence of the 5' end of the wheat gene is homologous with dicot psbA genes.
      We have located the 5' terminus of the wheat psbA RNA to a position 83 nt
      upstream of its coding region. The same psbA RNA species was capped in vitro by
      guanylyltransferase, establishing that its 5' end is a transcription start site.
      Regions which resemble procaryotic -10 and -35 promoter elements are located
      immediately upstream of the wheat psbA transcription initiation site. 

PMID- 24277562
TI  - The alpha1-tubulin gene of Arabidopsis thaliana: primary structure and
      preferential expression in flowers.
AB  - The primary structure of the alpha1-tubulin gene of Arabidopsis thaliana was
      determined and the 5' and 3' ends of its transcript were identified by S1
      nuclease mapping experiments. The information obtained was used to (i) predict
      the amino acid sequence of the alpha1-tubulin, (ii) deduce the positions of
      introns within the alpha1-tubulin gene, and (iii) construct 3' noncoding gene
      specific hybridization probes with which to study the pattern of alpha1-tubulin
      transcript accumulation in different tissues and at different stages of
      development. The predicted amino acid sequence of the alpha1-tubulin has 92%
      identity with the predicted product of the previously characterized A. thaliana
      alpha3-tubulin gene. The coding sequence of the alpha1-tubulin gene is
      interrupted by four introns located at positions identical to those of the four
      introns in the alpha3 gene. RNA blot hybridization studies carried out with an
      alpha1-tubulin gene-specific probe showed that the alpha1 gene transcript
      accumulates primarily in flowers, with little transcript present in RNA isolated
      from roots or leaves. In order to investigate the pattern of alpha-tubulin gene
      expression in developing flowers, RNA was isolated from flowers at five different
      stages of development: flower buds, unopened flowers with pollen, open flowers,
      flowers with elongating carpels, and green seed pods. RNA blot hybridizations
      performed with 3' noncoding gene-specific probes showed that the alpha3 tubulin
      gene transcript is present in flowers at all stages of development, whereas the
      alpha1-tubulin gene transcript could only be detected in RNA from unopened
      flowers with pollen, open flowers, and flowers with elongating carpels. 

PMID- 24277564
TI  - Daucus carota cells contain a dihydrofolate reductase: thymidylate synthase
      bifunctional polypeptide.
AB  - Dihydrofolate reductase (DHFR) and thymidylate synthase (TS) activities from cell
      suspension cultures of Daucus carota were shown to copurify on (NH4)2SO4
      fractionation, DEAE Sephadex and methotrexate-Sepharose affinity chromatography
      and to share approximately the same Mr(183 kDa and 185 kDa respectively) as
      judged by gel filtration on Sephacryl S-200.The copurified protein migrated as a
      single band on polyacrylamide gel electrophoresis under denaturing
      conditions.Both activities could be eluted from the same position of the native
      gel.Moreover, methotrexate-resistant cell lines which overproduce DHFR revealed
      to have a parallel higher level of TS. It is therefore proposed and discussed
      that in carrot, similarly to protozoa, TS and DHFR are present on a single
      bifunctional polypeptide of 58 kDa. 

PMID- 24277563
TI  - Nucleotide sequence of cDNA clones encoding the complete precursor for subunit
      delta of thylakoid-located ATP synthase from spinach.
AB  - The nucleotide sequence of the entire nuclear-encoded precursor for subunit delta
      of the ATP synthase from spinach thylakoid membranes was determined by cDNA
      sequencing. Appropriate recombinant DNAs were selected from pBR322 and lambda
      gt11 libraries made from polyadenylated RNA of greening spinach seedlings. The
      mature protein consists of 187 amino acid residues corresponding to a molecular
      weight of 20468. The precursor protein (257 amino acid residues; M r=27676) is
      probably processed between a Met-Val bond. The predicted secondary structure of
      the transit sequence (70 residues; 7.2 kDa) resembles that of the Rieske Fe/S
      polypeptide, but shows little similarity with those of stromal or luminal
      proteins. The comparison of the chloroplast delta amino acid sequence with the
      published delta sequences from respiratory ATP synthases of bacterial and
      mitochondrial sources and from the thylakoid ATP synthase of the cyanobacterium
      Synechococcus suggests substantial divergence at the genic level although
      structural elements appear to be remarkably conserved. 

PMID- 24277565
TI  - A chimeric transcript containing a 16 S rRNA and a potential mRNA in chloroplasts
      of Euglena gracilis.
AB  - The chloroplast genome of Euglena gracilis contains a supplementary gene for a 16
      S rRNA (s16 S rrn gene), which is not part of a complete rrn operon. An open
      reading frame (ORF406) is located downstream of the s16 S rrn gene. Chloroplast
      RNA was hybridized with cloned DNA fragments of this region and the hybrids were
      analysed by electron microscopy and S1-nuclease protection experiments. The s16 S
      rrn gene and the ORF406 are transcribed as one continuous 3.6 kb long RNA, which
      starts just upstream of the 5'-end of the s16 S rrn gene. The 3'-end occurs at
      multiple sites within a region of 700 bases downstream of the ORF. Northern blot
      analysis shows that the abundance of the transcript is comparable with that of
      other chloroplast mRNAs. 

PMID- 24277566
TI  - Sigma-like activity from mustard (Sinapis alba L.) chloroplasts conferring DNA
      binding and transcription specificity to E. coli core RNA polymerase.
AB  - A protein fraction which lacks DNA-binding activity itself, but confers enhanced
      protein-DNA complex formation to E. coli core RNA polymerase, was obtained from
      mustard chloroplasts by heparin Sepharose chromatography. Gel retardation and
      competition assays as well as DNase I footprinting experiments with a chloroplast
      DNA fragment containing the psbA promoter indicate that this reflects sequence
      specific binding. Transcription of the psbA template by E. coli core enzyme in
      the presence of the chloroplast fraction results in enhanced formation of
      transcripts of the size expected for correct initiation at the in vivo start
      site. We conclude that the chloroplast fraction reveals sigma-like activity with
      E. coli RNA polymerase and thus might contain factor(s) of equivalent function in
      chloroplast transcription. 

PMID- 24277567
TI  - The 5' flanking region of a barley B hordein gene controls tissue and
      developmental specific CAT expression in tobacco plants.
AB  - The 549 base pairs of the 5' flanking region of a barley seed storage protein (B1
      hordein) gene were linked to the reporter gene encoding chloramphenicol acetyl
      transferase (CAT). The chimaeric gene was transferred into tobacco plants using
      Agrobacterium tumefaciens. CAT enzyme activity was detected in the seeds, but not
      in the leaves, of the transgenic plants. Furthermore, enzyme activity was found
      only in the endosperm, and only from fifteen days after pollination. In contrast,
      the constitutive 19S promoter from cauliflower mosaic virus (CaMV) directed the
      expression of the CAT gene in the leaves as well as in both the endosperm and
      embryo and at all stages in seed development. 

PMID- 24277568
TI  - Characterization of the alfalfa (Medicago sativa) genome by DNA reassociation.

PMID- 24277569
TI  - The chalcone synthase multigene family of Petunia hybrida (V30): sequence
      homology, chromosomal localization and evolutionary aspects.
AB  - Chalcone synthase (CHS) genes in Petunia hybrida comprise a multigene family
      containing at least 7 complete members in the strain Violet 30 (V30). Based on a
      high sequence homology in both coding and non-coding sequence, a number of CHS
      genes can be placed into two subfamilies. By restriction fragment length
      polymorphism (RFLP) analysis it was shown that both chromosomes II and V carry
      one of these subfamilies, in addition to the other CHS genes identified so far.
      Members of a subfamily were found to be closely linked genetically. Analysis of
      the Petunia species that contributed to the hybrid nature of P. hybrida (P.
      axillaris, P. parodii, P. inflata and P. violacea) shows that none of the CHS
      gene clusters is specific for either one of the parents and therefore did not
      arise as a consequence of the hybridization. The number of CHS genes within a
      subfamily varies considerably among these Petunia species. From this we infer
      that the CHS subfamilies arose from very recent gene duplications. 

PMID- 24277570
TI  - Impact of cardiac comorbidity on early outcomes after pancreatic resection.
AB  - BACKGROUND: In patients undergoing pancreatic resection (PR), identification of
      subgroups at increased risk for postoperative complications can allow focused
      interventions that may improve outcomes. STUDY DESIGN: Patients undergoing PR
      from 2005-2010 were selected from the American College of Surgeons National
      Surgical Quality Improvement Program database and categorized as having any
      history of cardiac disease (angina, congestive heart failure (CHF), myocardial
      infarction (MI), cardiac stent, or bypass) or as having acute cardiac disease
      (symptoms of CHF or angina within 30 days or MI within 6 months). These variables
      were utilized to examine the relationship between cardiac disease and outcomes
      after PR. RESULTS: The rate of serious complications and perioperative mortality
      in patients with any history of cardiac disease vs. those without was 34 vs. 24 %
      (p < 0.001) and 4.5 vs. 2.0 % (p < 0.001), respectively, and in patients with
      acute cardiac disease compared to patients without was 37 vs. 25 % (p < 0.001)
      and 8.6 vs. 2.2 % (p < 0.001), respectively. In multivariate analysis, the two
      cardiac disease variables remained associated with mortality. CONCLUSIONS: In
      patients undergoing PR, cardiac disease is a significant risk factor for adverse
      outcomes. These observations are critical for meaningful informed consent in
      patients considering pancreatectomy.

PMID- 24277571
TI  - Tongue somatosensory-evoked potentials in microvascular decompression treated
      trigeminal neuralgia.
AB  - Somatosensory-evoked potentials of the tongue (tSSEP) provide useful information
      about trigeminal-afferent pathway. The aim of this study was to evaluate tSSEP in
      trigeminal neuralgia (TN) treatment with microvascular decompression. Two
      patients with trigeminal neuralgia refractory to conservative treatment underwent
      microvascular decompression of the trigeminal nerve. tSSEP was performed a month
      prior to surgery and in the month after the surgery in both patients. Pain
      frequency and tSSEP were analyzed before and after surgery. In both patients, a
      complete resolution of pain occurred. In patient 1, tSSEP latencies became
      shorter than before surgery and wave N1 appeared. The intensity of stimulation
      necessary to reach the threshold was 4 mA before the surgery and 1 mA after the
      surgery. A complete recovery of tSSEP after the operation was achieved in patient
      2. The results of present study demonstrate potential value of tSSEP in pre
      surgery evaluation and post-surgery follow-up of TN patients.

PMID- 24277572
TI  - Breast cancer brain metastases: a review of the literature and a current
      multidisciplinary management guideline.
AB  - Breast cancer represents the second most frequent etiology of brain metastasis
      (BM). It is estimated that 10-30 % of patients with breast cancer are diagnosed
      with BM. Breast cancer BM are increasing due to the aging population, detection
      of subclinical disease, and better control of systemic disease. BM is a major
      cause of morbidity and mortality affecting neurocognition, speech, coordination,
      behavior, and quality of life. The therapy of BM remains controversial regarding
      use and timing of surgical resection, application of whole-brain radiotherapy,
      stereotactic radiosurgery and systemic drugs in patients with particular tumor
      subtypes. Despite numerous trials, the range of interpretation of these has
      resulted in differing treatment perspectives. This paper is a review of the state
      of the art and a multidisciplinary guideline on strategies to improve the
      therapeutic index in this situation.

PMID- 24277574
TI  - Self-assembly of soft hybrid materials directed by light and a magnetic field.
AB  - Dual-responsive soft matter: A soft hybrid material composed of superparamagnetic
      nanoparticles and cyclodextrin vesicles self-assembles in microscale linear
      aggregates in water in response to magnetic field as well as light. 

PMID- 24277573
TI  - Lung cancer in women: an overview with special focus on Spanish women.
AB  - Lung cancer incidence is decreasing worldwide among men but rising among women
      due to recent changes in smoking patterns in both sexes. In Europe, the smoking
      epidemic has evolved different rates and times, and policy responses to it, vary
      substantially between countries. Differences in smoking prevalence are much more
      evident among European women reflecting the heterogeneity in cancer incidence
      rates. Other factors rather than smoking and linked to sex may increase women's
      susceptibility to lung cancer, such as genetic predisposition, exposure to sex
      hormones and molecular features, all of them linked to epidemiologic and clinical
      characteristics of lung cancer in women. However, biological bases of sex
      specific differences are controversial and need further evaluation. This review
      focuses on the epidemiology and outcome concerning non-small cell lung cancer in
      women, with emphasis given to the Spanish population. 

PMID- 24277575
TI  - Integrin-mediated cell surface recruitment of autotaxin promotes persistent
      directional cell migration.
AB  - Autotaxin (ATX) is a secreted lysophospholipase D (lysoPLD) that binds to
      integrin adhesion receptors. We dissected the roles of integrin binding and
      lysoPLD activity in stimulation of human breast cancer and mouse aortic vascular
      smooth muscle cell migration by ATX. We compared effects of wild-type human ATX,
      catalytically inactive ATX, an integrin binding-defective ATX variant with wild
      type lysoPLD activity, the isolated ATX integrin binding N-terminal domain, and a
      potent ATX selective lysoPLD inhibitor on cell migration using transwell and
      single-cell tracking assays. Stimulation of transwell migration was reduced (18
      or 27% of control, respectively) but not ablated by inactivation of integrin
      binding or inhibition of lysoPLD activity. The N-terminal domain increased
      transwell migration (30% of control). ATX lysoPLD activity and integrin binding
      were necessary for a 3.8-fold increase in the fraction of migrating breast cancer
      cell step velocities >0.7 MUm/min. ATX increased the persistent directionality of
      single-cell migration 2-fold. This effect was lysoPLD activity independent and
      recapitulated by the integrin binding N-terminal domain. Integrin binding enables
      uptake and intracellular sequestration of ATX, which redistributes to the front
      of migrating cells. ATX binding to integrins and lysoPLD activity therefore
      cooperate to promote rapid persistent directional cell migration.

PMID- 24277576
TI  - Estrogen-related receptor-alpha (ERRalpha) deficiency in skeletal muscle impairs
      regeneration in response to injury.
AB  - The estrogen-related receptor-alpha (ERRalpha) regulates mitochondrial biogenesis
      and glucose and fatty acid oxidation during differentiation in skeletal myocytes.
      However, whether ERRalpha controls metabolic remodeling during skeletal muscle
      regeneration in vivo is unknown. We characterized the time course of skeletal
      muscle regeneration in wild-type (M-ERRalphaWT) and muscle-specific ERRalpha(-/-)
      (M-ERRalpha(-/-)) mice after injury by intramuscular cardiotoxin injection. M
      ERRalpha(-/-) mice exhibited impaired regeneration characterized by smaller
      myofibers with increased centrally localized nuclei and reduced mitochondrial
      density and cytochrome oxidase and citrate synthase activities relative to M
      ERRalphaWT. Transcript levels of mitochondrial transcription factor A, nuclear
      respiratory factor-2a, and peroxisome proliferator-activated receptor (PPAR)
      gamma coactivator (PGC)-1beta, were downregulated in the M-ERRalpha(-/-) muscles
      at the onset of myogenesis. Furthermore, coincident with delayed myofiber
      recovery, we observed reduced muscle ATP content (-45% vs. M-ERRalphaWT) and
      enhanced AMP-activated protein kinase (AMPK) activation in M-ERRalpha(-/-)
      muscle. We subsequently demonstrated that pharmacologic postinjury AMPK
      activation was sufficient to delay muscle regeneration in WT mice. AMPK
      activation induced ERRalpha transcript expression in M-ERRalphaWT muscle and in
      C2C12 myotubes through induction of the Esrra promoter, indicating that ERRalpha
      may control gene regulation downstream of the AMPK pathway. Collectively, these
      results suggest that ERRalpha deficiency during muscle regeneration impairs
      recovery of mitochondrial energetic capacity and perturbs AMPK activity,
      resulting in delayed myofiber repair.

PMID- 24277577
TI  - Adenylyl cyclase 6 mediates loading-induced bone adaptation in vivo.
AB  - Primary cilia are single, nonmotile, antenna-like structures extending from the
      apical membrane of most mammalian cells. They may mediate mechanotransduction,
      the conversion of external mechanical stimuli into biochemical intracellular
      signals. Previously we demonstrated that adenylyl cyclase 6 (AC6), a membrane
      bound enzyme enriched in primary cilia of MLO-Y4 osteocyte-like cells, may play a
      role in a primary cilium-dependent mechanism of osteocyte mechanotransduction in
      vitro. In this study, we determined whether AC6 deletion impairs loading-induced
      bone formation in vivo. Skeletally mature mice with a global knockout of AC6
      exhibited normal bone morphology and responded to osteogenic chemical stimuli
      similar to wild-type mice. Following ulnar loading over 3 consecutive days, bone
      formation parameters were assessed using dynamic histomorphometry. Mice lacking
      AC6 formed significantly less bone than control animals (41% lower bone formation
      rate). Furthermore, there was an attenuated flow-induced increase in COX-2 mRNA
      expression levels in primary bone cells isolated from AC6 knockout mice compared
      to controls (1.3+/-0.1- vs. 2.6+/-0.2-fold increase). Collectively, these data
      indicate that AC6 plays a role in loading-induced bone adaptation, and these
      findings are consistent with our previous studies implicating primary cilia and
      AC6 in a novel mechanism of osteocyte mechanotransduction.

PMID- 24277578
TI  - Collagen VI regulates peripheral nerve myelination and function.
AB  - Collagen VI is an extracellular matrix protein with broad distribution in several
      tissues. Although Col6a1 is expressed by Schwann cells, the role of collagen VI
      in the peripheral nervous system (PNS) is yet unknown. Here we show that Schwann
      cells, but not axons, contribute to collagen VI deposition in peripheral nerves.
      By using Col6a1-null mice, in which collagen VI deposition is compromised, we
      demonstrate that lack of collagen VI leads to increased myelin thickness
      (P<0.001) along with 60-130% up-regulation in myelin-associated proteins and
      disorganized C fibers in the PNS. The hypermyelination of PNS in Col6a1(-/-) mice
      is supported by alterations of signaling pathways involved in myelination,
      including increase of P-FAK, P-AKT, P-ERK1, P-ERK2, and P-p38 (4.15, 1.67, 2.47,
      3.34, and 2.60-fold, respectively) and reduction of vimentin (0.49-fold), P-JNK
      (0.74-fold), and P-c-Jun (0.50-fold). Pathologically, Col6a1(-/-) mice display an
      impairment of nerve conduction velocity and motor coordination (P<0.05), as well
      as a delayed response to acute pain stimuli (P<0.001), indicating that lack of
      collagen VI causes functional defects of peripheral nerves. Altogether, these
      results indicate that collagen VI is a critical component of PNS contributing to
      the structural integrity and proper function of peripheral nerves.

PMID- 24277579
TI  - A self-report measure of pubertal status: Reliability, validity, and initial
      norms.
AB  - Puberty is a central process in the complex set of changes that constitutes the
      transition from childhood to adolescence. Research on the role of pubertal change
      in this transition has been impeded by the difficulty of assessing puberty in
      ways acceptable to young adolescents and others involved. Addressing this
      problem, this paper describes and presents norms for a selfreport measure of
      pubertal status. The measure was used twice annually over a period of three years
      in a longitudinal study of 335 young adolescent boys and girls. Data on a
      longitudinal subsample of 253 subjects are reported. The scale shows good
      reliability, as indicated by coefficient alpha. In addition, several sources of
      data suggest that these reports are valid. The availability of such a measure is
      important for studies, such as those based in schools, in which more direct
      measures of puberty may not be possible. 

PMID- 24277580
TI  - The influence of divorce on coping in adolescence.
AB  - The present study explored the relations between family status and coping
      processes in adolescence. Given the inconsistent findings with regard to the
      divorce experience, our intent was to determine if coping strategies endorsed by
      adolescents are related to family status. Further, appraisals of stressfulness,
      controllability, and perceived outcome of stressful situations were examined in
      relation to family status and coping strategies endorsed. Adolescents of divorced
      parents more frequently endorsed theoretically less mature, defensive coping
      strategies. Sex differences were noted in the intact group, while males and
      females in the divorce group were more alike in their coping responses. Appraisal
      variables were differentially related to coping behaviors in each group. 

PMID- 24277581
TI  - Perception and experience of types of social stress and self-image among
      adolescents.
AB  - Eighty-four 16-18-year-old male and female volunteers were sampled to test the
      relationship of ratings and experience of four types of social stressors
      (developmental transitions, induced transitions, daily hassles, and circumscribed
      events). Also the relationship of self-image as measured by the Offer Self-Image
      Questionnaire to each type of stressor was studied. Contrary to previous
      research, we did not find correlations between ratings and experience, and
      observed minimal gender differences in ratings, experience levels, and
      psychopathology. Several differences in impact were found when stressor types
      were differentiated. Apparently, developmental transitions are least stressful
      for adolescents and daily hassles are most influential on their self-image.
      Gender differences were noted in the perceived change required by types of
      stressors and the manner in which stressors impacted on self-image. These results
      suggest that it is important to distinguish type of Stressors by type of
      adjustment process required, and that previously reported gender differences are
      less a matter of global differences or affects of specific Stressors than a
      matter of variations in perceived adjustment required and aspect of functioning
      impacted. 

PMID- 24277582
TI  - Social drinking in supportive contexts among college males.
AB  - Two hundred and five male college students were administered a number of self
      report questionnaires to assess the role of social drinking in their social
      support processes. Results indicated that the quantity and frequency of social
      drinking was positively related to seven of the ten social support variables
      associated with male social network members, but only one of ten female support
      variables. Other results showed that subjects obtained half of their
      companionship support in social drinking encounters, as well as over a quarter of
      their emotional support and one fifth of their material assistance and problem
      solving support. Further analysis demonstrated that the male subjects received a
      higher proportion of all types of support while drinking when the support sources
      were male than compared to when they were female. These results are consistent
      with previous studies, which found that social drinking and social support are
      positively related. Social drinking seems to play an important role in the social
      support processes of college males, especially when other males are involved. 

PMID- 24277583
TI  - Identity formation and social relations during late adolescence.
AB  - Theoretical assumptions outlined by Erik Erikson on psychosocial crisis
      resolution hypothesizes that the positive resolution of the identity crisis is
      predictive of more mature intimacy formation. To test this hypothesis, college
      aged late adolescents (48 subjects) completed interviews and selfreport
      instruments measuring identity formation and degree of intimacy along with daily
      records of social interactions for one week. Analyses indicated a complex
      association between identity and intimacy formation. Comparisons were made
      between the exploration and commitment process of identity and the measures of
      intimacy formation and social interaction measures. Numerous complex sex
      differences were observed with several interactions between gender, exploration,
      commitment, and intimacy context. Findings are discussed in terms of broadening
      future research direction beyond the simple study of the linkage of identity and
      intimacy. 

PMID- 24277584
TI  - Moral judgment and sex role orientation as a function of self and other
      presentation mode.
AB  - Gilligan's concern for a negative bias in assessing moral reasoning based on
      feminine interpersonal orientations and corresponding positive bias in favor of
      masculine orientations of justice and equity was explored. Bem's Sex Role
      Inventory provided a psychological index of orientation rather than only
      biological sex. College men and women completed Rest's moral dilemmas (DIT) in
      the usual manner-other condition-or assumed the role of the central character
      self condition. The latter procedure augmented affective dimensions assumed to
      underlie orientation differences. Males in the other condition scored higher on
      the DIT than those in the self condition; females revealed the opposite pattern.
      Using the sex role categories, it appeared that androgynous males had higher DIT
      scores in the self condition than in the other condition, in direct contrast to
      the overall results for males. For females who were androgynous or masculine in
      orientation, the self condition resulted in higher DIT scores than the other
      condition. Generally, the greater affective demands in the self condition
      produced a higher frequency of Stage 3 use for men and women regardless of sex
      role orientation. The other condition showed a higher percentage of Stage 4 use
      among males and females independent of sex role orientation. Sex role orientation
      and affective arousal were discussed in terms of Gilligan's view of moral
      judgment development. 

PMID- 24277585
TI  - beta-Dicalcium silicate-based cement: synthesis, characterization and in vitro
      bioactivity and biocompatibility studies.
AB  - beta-dicalcium silicate (beta-Ca2 SiO4, beta-C2 S) is one of the main
      constituents in Portland cement clinker and many refractory materials, itself is
      a hydraulic cement that reacts with water or aqueous solution at room/body
      temperature to form a hydrated phase (C-S-H), which provides mechanical strength
      to the end product. In the present investigation, beta-C2 S was synthesized by
      sol-gel process and it was used as powder to cement preparation, named CSiC. In
      vitro bioactivity and biocompatibility studies were assessed by soaking the
      cement samples in simulated body fluid solutions and human osteoblast cell
      cultures for various time periods, respectively. The results showed that the sol
      gel process is an available synthesis method in order to obtain a pure powder of
      beta-C2 S at relatively low temperatures without chemical stabilizers. A bone
      like apatite layer covered the material surface after soaking in SBF and its
      compressive strength (CSiC cement) was comparable with that of the human
      trabecular bone. The extracts of this cement were not cytotoxic and the cell
      growth and relative cell viability were comparable to negative control.

PMID- 24277586
TI  - Unmasking risk loci: DNA methylation illuminates the biology of cancer
      predisposition: analyzing DNA methylation of transcriptional enhancers reveals
      missed regulatory links between cancer risk loci and genes.
AB  - Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate
      with the expression of cancer genes. Therefore, the molecular mechanism
      underlying an individual's susceptibility to cancer has remained largely unknown.
      However, recent evaluations of the correlations between DNA methylation and gene
      expression levels across healthy and cancerous genomes have revealed enrichment
      of disease-related DNA methylation variations within disease-associated risk
      loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk
      loci often contain DNA methylation sites that closely define the expression of
      prominent cancer genes, despite the lack of significant correlations between gene
      expression levels and the surrounding disease-associated polymorphic sequences.
      We suggest that DNA methylation variations may obscure the effect of co-residing
      risk sequence alleles. Analysis of enhancer methylation data may help to reveal
      the regulatory circuits underlying predisposition to cancers and other common
      diseases.

PMID- 24277587
TI  - Visualization of bioluminescence as a marker of gene expression in rhizobium
      infected soybean root nodules.
AB  - The linked structural genes lux A and lux B, encoding bacterial luciferase of a
      marine bacterium Vibrio harveyi, were fused with the nitrogenase nifD promoter
      from Bradyrhizobium japonicum and with the P1 promoter of pBR322. Both fusions
      were integrated into the B. japonicum chromosome by site-specific recombination.
      Soybean roots infected with the two types of rhizobium transconjugants formed
      nitrogen-fixing nodules that produced bright blue-green light. Cells containing
      the P1 promoter/lux AB fusion resulted in continuously expressed bioluminescence
      in both free-living rhizobium and in nodule bacteriods. However, when under
      control of the nifD promoter, luciferase activity was found only in introgen
      fixing nodules. Light emission from bacteroids allowed us to visualize and to
      photograph nodules expressing this marker gene fusion in vivo at various levels
      of resolution, including within single, living plant cells. Localization of host
      cells containing nitrogen-fixing bacteroids within nodule tissue was accomplished
      using low-light video microscopy aided by realtime image processing techniques
      developed specifically to enhance extreme low-level luminescent images. 

PMID- 24277588
TI  - Isolation and characterization of a tomato cDNA clone which codes for a salt
      induced protein.
AB  - The cDNA clone (pNP24) coding for a protein induced by exogenous NaCl has been
      isolated from a tomato root cDNA library with the use of an inosine containing
      synthetic oligomer. The authenticity of the clone has been established by
      comparing the sequence of the clone to the NH2-terminal sequence of the protein
      which has been purified to homogeneity by HPLC. The nucleotide sequence of pNP24
      reveals a 5' signal sequence, an open reading frame of 718 nucleotides, a 3' AT
      rich untranslated region containing a probable polyadenylation signal sequence,
      and a poly A stretch. The mature polypeptide sequence as deduced from the
      nucleotide sequence reveals a protein with a molecular weight of 24226. This
      protein has been named NP24. It is slightly basic and has an unusually high
      number of cysteines (15). Northern blot analyses reveal that the abundance of
      mRNA for NP24 is at least 100-fold greater in tomato suspension cells in log
      phase grown in medium with NaCl than in cells grown in the control medium. The
      mRNA for NP24 is below the level of detection in roots of young control tomato
      plants until several weeks after germination but it is induced earlier and to
      higher levels in roots stressed by 0.171 M NaCl. Thus salt stress accelerates the
      accumulation of message in tomato roots. A comparison of the steady state levels
      of mRNA for NP24 to the accumulation of NP24 by immuno analyses indicates that
      the accumulation of this protein is determined by its mRNA level. The protein is
      not secreted and is localized within the cytoplasm or the soluble fraction of the
      nucleus, vacuole, or microbodies. NP24 has a high degree of homology (58%) with
      thaumatin, a protein which has considerable value as an artificial sweetener. 

PMID- 24277589
TI  - Proximity of an ARS consensus sequence to a replication origin of pea (Pisum
      sativum).
AB  - The replication origin (ori-r9) of the 9.0 kb rDNA repeats of pea (Pisum sativum,
      cv. Alaska) was cloned and found to reside in a 1.5 kb fragment of the non
      transcribed spacer region located between the 25 S and 18 S genes. Labeled rDNA
      rich in replication forks, from cells positioned at the G1/S phase boundary, was
      used to map ori-r9 by hybridization procedures. Ori-r9 is in a 210-base fragment
      that is 1.6 kb from the 5' end of the 18 S gene and about 1.5 kb from the 3' end
      of the 25 S gene. The same procedures, using labeled synthetic ARS consensus
      sequence as a probe, showed than an ARS consensus sequence is located 3' to ori
      r9 in a 710-base fragment. An ARS consensus sequence is, therefore, adjacent to
      ori-r9 but not coincidental with it. 

PMID- 24277590
TI  - CR1 - a dispersed repeated element associated with the Cab-1 locus in tomato.
AB  - Cab-1 is a complex genetic locus in tomato consisting of four clustered genes
      encoding chlorophyll a/b-binding polypeptide. Southern blot analysis of total
      tomato DNA with genomic clones corresponding to the Cab-1 locus has revealed the
      presence of a repetitive element in the 3 kb spacer regions between two of these
      genes. This repetitive element, named CR1, has been characterized via sequencing,
      genetic mapping and hybridization to related solanaceous species. Results
      indicate that there are as many as 30 copies of this element in the tomato genome
      and that most, if not all, are found at independent loci. Sites corresponding to
      12 of the repeats have been located on different regions of chromosomes 2, 4, 5,
      7, 10 and 11. A 1.6 kb PstI-EcoRI fragment from the Cab-1 locus containing the
      element was sequenced and found to be 75% AT-rich. No open reading frames larger
      than 150 bp were detected. Several imperfect inverted repeats flanked by direct
      repeats could be found at the ends of the element. This arrangement is
      reminiscent of known transposons. Southern hybridization analysis indicates that
      multiple copies of CR1 exist in all species of the genus Lycopersicon as well as
      in Solanum lycopersicoides and S. tuberosum (potato), but not in eggplant,
      pepper, petunia, Datura or tobacco. Melt-off experiments indicate that members of
      the CR1 family in the tomato genome are more closely related to one another than
      to homologous members in the genomes of S. lycopersicoides or S. tuberosum,
      suggesting some type of concerted evolution. 

PMID- 24277591
TI  - Isolation and sequence of a tomato cDNA clone encoding subunit II of the
      photosystem I reaction center.
AB  - We report here the isolation and nucleotide sequence of a cDNA clone encoding a
      phtosystem I polypeptide that is recognized by a polyclonal antibody prepared
      against subunit II of the photosystem I reaction center. The transit peptide
      processing site was determined to occur after Met50 by N terminal sequencing. The
      decuced sequence of this protein predicts that the polypeptide has a net positive
      charge (pI=9.6) and no membrane spanning regions are evident from the hydropathy
      plot. Based on these considerations and the fact that subunit II is solubilized
      by alkali treatment of thylakoids, we concluded that subunit II is an extrinsic
      membrane protein. The absence of hydrophobic regions characteristic of thylakoid
      transfer domains furthermore implies that subunit II is localized on the stromal
      side of the membrane. 

PMID- 24277592
TI  - Transcription study of the genes encoded in the region of the junction between
      the large single copy and the inverted repeat A of spinach chloroplast DNA.
AB  - The expression of the psbA, trnH-GUG and rps19' genes from spinach chloroplasts,
      coding respectively for the 32 kDa protein, the tRNA(His) (GUG), and the putative
      ribosomal protein CS19', has been studied by cloning, Northern hybridization and
      3' and 5' S1 mapping experiments.It is demonstrated that the putative
      transcription termination signal of the psbA gene does not function as a rho
      independent terminator of transcription in E. coli, whatever its
      orientation.Evidence is presented suggesting that, in spinach, the psbA and trnH
      GUG genes are probably cotranscribed. The 3'-OH extremities of transcripts
      observed downstream from the putative psbA terminator are interpreted as
      resulting from processing of the psbA precursor.Using different approaches, it is
      shown that the rps19' gene, located on the other strand and overlapping the trnH
      GUG gene, is not expressed. 

PMID- 24277593
TI  - Identification of an Escherichia coli S1-like protein in the spinach chloroplast
      ribosome.
AB  - Antibodies directed against E. coli ribosomal protein S1 were used in
      immunoblotting assays to search for an S1-like protein in the ribosome of spinach
      chloroplast. An immunological cross-reaction was reproducibly detected on the
      blots and inhibition experiments have demonstrated its specificity. The
      chloroplastic ribosomal protein which has epitopes common to antigenic
      determinants of the E. coli protein S1 was identified as being protein S2/S3. 

PMID- 24277594
TI  - Sequence of the plastid rDNA spacer region of the brown alga Pylaiella littoralis
      (L.) Kjellm. Evolutionary significance.
AB  - The DNA segment situated between the 16S and 23S rRNA genes belonging to the
      plastid genome of the brown alga Pylaiella littoralis (L.) Kjellm. has been
      sequenced. This small region (322 bp) contains two unsplit tRNA genes separated
      by 3 bp. A comparison with similar regions from different plants shows that this
      region has evolved in two different ways according to the place of plants in
      evolution. In the "primitive" group, this region is reduced in size when compared
      to prokaryotes. In the other groups, it is considerably enlarged by insertion of
      repetitive sequences, open reading frames and introns. 

PMID- 24277595
TI  - Cloning and nucleotide sequence of a soybean gene encoding a light-harvesting
      chlorophyll a/b-binding protein of Photosystem II.

PMID- 24277596
TI  - Tuberculosis of the eye in Italy: a forgotten extrapulmonary localization.
AB  - PURPOSE: Tuberculosis (TB) of the eye is a well-known extrapulmonary localization
      in high-incidence countries. Data on its relevance in developed countries are
      scanty. We aim to study the epidemiological and clinical pattern of ocular TB in
      a tertiary care institution of a western country. METHODS: From 2007 to 2010,
      consecutive patients with a diagnosis of isolated ocular TB or associated to
      extraocular TB were recruited. Patients with ophthalmological and clinical
      features of TB were treated with standard antitubercular therapy (ATT) and
      steroids in case of concomitant severe ocular inflammation. RESULTS: Seventeen
      cases of ocular and extraocular TB and 45 cases of isolated ocular TB were
      identified. The proportion of patients with ocular and extraocular TB in our
      local district was 8.1 %, with a proportion of 10.6 % for the isolated cases. In
      Cohort 1, only one patient was symptomatic for ocular impairment, and uveitis
      without inflammation was the most common presentation. On the contrary, in Cohort
      2, all patients had visual impairment, mainly with bilateral involvement. 77.8 %
      of the patients showed an inflammatory pattern. ATT was administered for at least
      9 months, in four cases with a short course of systemic corticosteroids. Eight
      cases in Cohort 2 showed recurrence after 1 year from diagnosis. CONCLUSIONS: TB
      of the eye should not be forgotten, even in geographical areas not considered
      among endemic countries. Ocular evaluation is advisable in patients with
      pulmonary and extrapulmonary TB, as early detection may allow ATT to preserve
      visual acuity.

PMID- 24277597
TI  - Epidemiology and risk factors for severe respiratory syncytial virus infections
      requiring pediatric intensive care admission in Hong Kong children.
AB  - PURPOSE: Respiratory syncytial virus (RSV) is a common cause of lower respiratory
      tract infection in young children. However, there are limited data on severe RSV
      infection requiring pediatric intensive care unit (PICU) admission. This
      retrospective study described features of RSV-associated PICU admissions in Hong
      Kong and investigated factors for mortality and duration of PICU stay. METHODS:
      Children with laboratory-confirmed RSV infection and admitted to the PICUs of all
      eight government hospitals in Hong Kong between January 2009 and June 2011 were
      identified from computerized auditing systems and PICU databases. RSV in
      respiratory samples was detected by direct immunofluorescence and/or viral
      culture. The relationships between mortality and PICU duration and demographic
      and clinical factors were analyzed. RESULTS: A total of 118 (2.4 %) PICU
      admissions were identified among 4,912 RSV-positive pediatric cases in all
      hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher
      between October and March. Eight (6.8 %) patients died, but only two were
      infants. RSV-associated mortality was related to prior sick contact, presence of
      older siblings, neurodevelopmental conditions, chromosomal and genetic diseases,
      and bacterial co-infections, but none was significant following logistic
      regression analyses (odds ratio 9.36, 95 % confidence interval 0.91-96.03 for
      prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for
      the duration of PICU admission (beta = 0.218, p = 0.017). CONCLUSIONS: The
      majority of RSV-infected children do not require PICU support. There is winter
      seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is
      the only risk factor for RSV-associated mortality, whereas the presence of
      chronic lung disease is associated with longer PICU stay. The current risk-based
      approach of RSV prophylaxis may not be effective in reducing severe RSV
      infections.

PMID- 24277599
TI  - Of fish oil, rafts, and scrambling things up.

PMID- 24277600
TI  - Hill's equation of muscle performance and its hidden insight on molecular
      mechanisms.
AB  - Muscles shorten faster against light loads than they do against heavy loads. The
      hyperbolic equation first used by A.V. Hill over seven decades ago to illustrate
      the relationship between shortening velocity and load is still the predominant
      method used to characterize muscle performance, even though it has been regarded
      as purely empirical and lacking precision in predicting velocities at high and
      low loads. Popularity of the Hill equation has been sustained perhaps because of
      historical reasons, but its simplicity is certainly attractive. The descriptive
      nature of the equation does not diminish its role as a useful tool in our quest
      to understand animal locomotion and optimal design of muscle-powered devices like
      bicycles. In this Review, an analysis is presented to illustrate the connection
      between the historic Hill equation and the kinetics of myosin cross-bridge cycle
      based on the latest findings on myosin motor interaction with actin filaments
      within the structural confines of a sarcomere. In light of the new data and
      perspective, some previous studies of force-velocity relations of muscle are
      revisited to further our understanding of muscle mechanics and the underlying
      biochemical events, specifically how extracellular and intracellular environment,
      protein isoform expression, and posttranslational modification of contractile and
      regulatory proteins change the interaction between myosin and actin that in turn
      alter muscle force, shortening velocity, and the relationship between them.

PMID- 24277601
TI  - Multilevel regulation: Controlling BK channels in central clock neurons.

PMID- 24277602
TI  - Phosphorylation of a constitutive serine inhibits BK channel variants containing
      the alternate exon "SRKR".
AB  - BK Ca(2+)-activated K(+) currents exhibit diverse properties across tissues. The
      functional variation in voltage- and Ca(2+)-dependent gating underlying this
      diversity arises from multiple mechanisms, including alternate splicing of
      Kcnma1, the gene encoding the pore-forming (alpha) subunit of the BK channel,
      phosphorylation of alpha subunits, and inclusion of beta subunits in channel
      complexes. To address the interplay of these mechanisms in the regulation of BK
      currents, two native splice variants, BK0 and BKSRKR, were cloned from a tissue
      that exhibits dynamic daily expression of BK channel, the central circadian
      pacemaker in the suprachiasmatic nucleus (SCN) of mouse hypothalamus. The BK0 and
      BKSRKR variants differed by the inclusion of a four-amino acid alternate exon at
      splice site 1 (SRKR), which showed increased expression during the day. The
      functional properties of the variants were investigated in HEK293 cells using
      standard voltage-clamp protocols. Compared with BK0, BKSRKR currents had a
      significantly right-shifted conductance-voltage (G-V) relationship across a range
      of Ca(2+) concentrations, slower activation, and faster deactivation. These
      effects were dependent on the phosphorylation state of S642, a serine residue
      within the constitutive exon immediately preceding the SRKR insert. Coexpression
      of the neuronal beta4 subunit slowed gating kinetics and shifted the G-V
      relationship in a Ca(2+)-dependent manner, enhancing the functional differences
      between the variants. Next, using native action potential (AP) command waveforms
      recorded from SCN to elicit BK currents, we found that these splice variant
      differences persist under dynamic activation conditions in physiological ionic
      concentrations. AP-induced currents from BKSRKR channels were significantly
      reduced compared with BK0, an effect that was maintained with coexpression of the
      beta4 subunit but abolished by the mutation of S642. These results demonstrate a
      novel mechanism for reducing BK current activation under reconstituted
      physiological conditions, and further suggest that S642 is selectively
      phosphorylated in the presence of SRKR.

PMID- 24277604
TI  - Febrile temperatures unmask biophysical defects in Nav1.1 epilepsy mutations
      supportive of seizure initiation.
AB  - Generalized epilepsy with febrile seizures plus (GEFS+) is an early onset febrile
      epileptic syndrome with therapeutic responsive (a)febrile seizures continuing
      later in life. Dravet syndrome (DS) or severe myoclonic epilepsy of infancy has a
      complex phenotype including febrile generalized or hemiclonic convulsions before
      the age of 1, followed by intractable myoclonic, complex partial, or absence
      seizures. Both diseases can result from mutations in the Nav1.1 sodium channel,
      and initially, seizures are typically triggered by fever. We previously
      characterized two Nav1.1 mutants-R859H (GEFS+) and R865G (DS)-at room temperature
      and reported a mixture of biophysical gating defects that could not easily
      predict the phenotype presentation as either GEFS+ or DS. In this study, we
      extend the characterization of Nav1.1 wild-type, R859H, and R865G channels to
      physiological (37 degrees C) and febrile (40 degrees C) temperatures. At
      physiological temperature, a variety of biophysical defects were detected in both
      mutants, including a hyperpolarized shift in the voltage dependence of activation
      and a delayed recovery from fast and slow inactivation. Interestingly, at 40
      degrees C we also detected additional gating defects for both R859H and R865G
      mutants. The GEFS+ mutant R859H showed a loss of function in the voltage
      dependence of inactivation and an increased channel use-dependency at 40 degrees
      C with no reduction in peak current density. The DS mutant R865G exhibited
      reduced peak sodium currents, enhanced entry into slow inactivation, and
      increased use-dependency at 40 degrees C. Our results suggest that fever-induced
      temperatures exacerbate the gating defects of R859H or R865G mutants and may
      predispose mutation carriers to febrile seizures.

PMID- 24277603
TI  - Binding of the auxiliary subunit TRIP8b to HCN channels shifts the mode of action
      of cAMP.
AB  - Hyperpolarization-activated cyclic nucleotide-regulated cation (HCN) channels
      generate the hyperpolarization-activated cation current Ih present in many
      neurons. These channels are directly regulated by the binding of cAMP, which both
      shifts the voltage dependence of HCN channel opening to more positive potentials
      and increases maximal Ih at extreme negative voltages where voltage gating is
      complete. Here we report that the HCN channel brain-specific auxiliary subunit
      TRIP8b produces opposing actions on these two effects of cAMP. In the first
      action, TRIP8b inhibits the effect of cAMP to shift voltage gating, decreasing
      both the sensitivity of the channel to cAMP (K1/2) and the efficacy of cAMP
      (maximal voltage shift); conversely, cAMP binding inhibits these actions of
      TRIP8b. These mutually antagonistic actions are well described by a cyclic
      allosteric mechanism in which TRIP8b binding reduces the affinity of the channel
      for cAMP, with the affinity of the open state for cAMP being reduced to a greater
      extent than the cAMP affinity of the closed state. In a second apparently
      independent action, TRIP8b enhances the action of cAMP to increase maximal Ih.
      This latter effect cannot be explained by the cyclic allosteric model but results
      from a previously uncharacterized action of TRIP8b to reduce maximal current
      through the channel in the absence of cAMP. Because the binding of cAMP also
      antagonizes this second effect of TRIP8b, application of cAMP produces a larger
      increase in maximal Ih in the presence of TRIP8b than in its absence. These
      findings may provide a mechanistic explanation for the wide variability in the
      effects of modulatory transmitters on the voltage gating and maximal amplitude of
      Ih reported for different neurons in the brain.

PMID- 24277605
TI  - DNA substrate preparation for atomic force microscopy studies of protein-DNA
      interactions.
AB  - Protein-DNA interactions provide fundamental control mechanisms over biologically
      essential processes such as DNA replication, transcription, and repair. However,
      many details of these mechanisms still remain unclear. Atomic force microscopy
      (AFM) analyses provide unique and important structural and functional information
      on such protein-DNA interactions at the level of the individual molecules. The
      high sensitivity of the method with topographical visualization of all sample
      components also demands for extremely clean and pure materials. Here, we provide
      an overview of molecular biology-based approaches to produce DNA substrates for
      AFM imaging as well as other types of experiments, such as optical or magnetic
      tweezers, that profit from controllable substrate properties in long DNA
      fragments. We present detailed strategies to produce different types of motifs in
      DNA that are frequently employed targets of protein interactions. Importantly,
      the presented preparation techniques imply exact knowledge of the location of the
      introduced specific target sites within the DNA fragments, allowing for a
      distinction between specific and non-specific protein-DNA interactions in the AFM
      images and for separate conformational analyses of the different types of protein
      DNA complexes.

PMID- 24277606
TI  - Proteome wide evaluation of the separation ability of hydrophobic interaction
      chromatography by fluorescent dye binding analysis.
AB  - Hydrophobic interaction chromatography (HIC) is an important tool in the
      industrial purification of proteins from various sources. The HIC separation
      behavior of individual (or model) proteins has been widely researched by others.
      On the contrary, this study focused on the fractionation ability of HIC when it
      is challenged with whole proteomes. The impact of the nature of three different
      proteomes, that is, yeast, soybean, and Chinese hamster ovary cells, on HIC
      separation was investigated. In doing so, chromatography fractions obtained under
      standardized conditions were evaluated in terms of their overall hydrophobicity-
      as measured by fluorescence dye binding. This technique allowed for the
      calculation of an average protein surface hydrophobicity (S(0)) for each
      fraction; a unique correlation between S(0) and the observed chromatographic
      behavior was established in each case. Following a similar strategy, the effect
      of three different ligands (polypropylene glycol, phenyl, and butyl) and two
      adsorbent particle sizes (65 and 100 um) on the chromatographic behavior of the
      yeast proteome was evaluated. As expected, the superficial hydrophobicity of the
      proteins eluted is correlated with the salt concentration of its corresponding
      elution step. The findings reveled how--and in which extent--the type of ligand
      and the size of the beads actually influenced the fractionation of the complex
      biological mixture. Summarizing, the approach presented here can be instrumental
      to the study of the performance of chromatography adsorbents under conditions
      close to industrial practice and to the development of downstream processing
      strategies.

PMID- 24277607
TI  - Visualization of the membrane engineering concept: evidence for the specific
      orientation of electroinserted antibodies and selective binding of target
      analytes.
AB  - Membrane engineering is a generic methodology for increasing the selectivity of a
      cell biosensor against a target molecule, by electroinserting target-specific
      receptor-like molecules on the cell surface. Previous studies have elucidated the
      biochemical aspects of the interaction between various analytes (including
      viruses) and their homologous membrane-engineered cells. In the present study,
      purified anti-biotin antibodies from a rabbit antiserum along with in-house
      prepared biotinylated bovine serum albumin (BSA) were used as a model antibody
      antigen pair of molecules for facilitating membrane engineering experiments. It
      was proven, with the aid of fluorescence microscopy, that (i) membrane-engineered
      cells incorporated the specific antibodies in the correct orientation and that
      (ii) the inserted antibodies are selectively interacting with the homologous
      target molecules. This is the first time the actual working concept of membrane
      engineering has been visualized, thus providing a final proof of the concept
      behind this innovative process. In addition, the fluorescence microscopy
      measurements were highly correlated with bioelectric measurements done with the
      aid of a bioelectric recognition assay.

PMID- 24277608
TI  - Molecularly imprinted cryogels for human interferon-alpha purification from human
      gingival fibroblast culture.
AB  - Interferons are important proteins for the immune system because of their
      antiviral, anti-proliferating and immunomodulatory activities. Therapeutic value
      of these proteins against certain types of tumors caused interest and
      investigations aimed to obtain highly purified interferons. Molecular imprinting
      is an efficient method for purification with high selectivity, specificity and
      good reproducibility. In this study, we utilized advantages of molecular
      imprinting technique for the purification of interferon from human gingival
      fibroblast culture. For this purpose, interferon alpha-2b imprinted
      poly(hydroxyethyl methacrylate) cryogel (hIFN-alpha-MIP) was prepared. Optimum
      adsorption conditions were determined, and maximum adsorption capacity of hIFN
      alpha-MIP cryogel was found as 254.8 * 10(4)  IU/g from aqueous solution. All
      interferon measurements are expressed as International Unit (IU), which is a unit
      measurement used to quantify biologically active substances like interferon based
      on their biological activity or effect. Selectivity experiments were performed
      using competitive proteins and repeated adsorption-desorption studies showed that
      the adsorption capacity maintained almost at a constant value after ten cycles.
      For the purification of interferon from human gingival fibroblast culture, fast
      protein liquid chromatography was used and the specific activity of the purified
      interferon alpha-2b on HeLa cell line was found between the values 3.45 * 10(8) 
      IU/mg and 3.75 * 10(8)  IU/mg. The results are promising, and the molecular
      imprinting technique is effective for the purification of interferon alpha-2b.

PMID- 24277609
TI  - Insulin receptor-insulin interaction kinetics using multiplex surface plasmon
      resonance.
AB  - Type 2 diabetes affects millions of people worldwide, and measuring the kinetics
      of insulin receptor-insulin interactions is critical to improving our
      understanding of this disease. In this paper, we describe, for the first time, a
      rapid, real-time, multiplex surface plasmon resonance (SPR) assay for studying
      the interaction between insulin and the insulin receptor ectodomain, isoform A
      (eIR-A). We used a scaffold approach in which anti-insulin receptor monoclonal
      antibody 83-7 (Abcam, Cambridge, UK) was first immobilized on the SPR sensorchip
      by amine coupling, followed by eIR-A capture. The multiplex SPR system (ProteOn
      XPR36TM, Bio-Rad Laboratories, Hercules, CA) enabled measurement of replicate
      interactions with a single, parallel set of analyte injections, whereas repeated
      regeneration of the scaffold between measurements caused variable loss of
      antibody activity. Interactions between recombinant human insulin followed a two
      site binding pattern, consistent with the literature, with a high-affinity site
      (dissociation constant K(D1)  = 38.1 +/- 0.9 nM) and a low-affinity site (K(D2) 
      = 166.3 +/- 7.3 nM). The predominantly monomeric insulin analogue Lispro had
      corresponding dissociation constants K(D1)  = 73.2 +/- 1.8 nM and K(D2)  = 148.9
      +/- 6.1 nM, but the fit to kinetic data was improved when we included a
      conformational change factor in which the high-affinity site was converted to the
      low-affinity site. The new SPR assay enables insulin-eIR-A interactions to be
      followed in real time and could potentially be extended to study the effects of
      humoral factors on the interaction, without the need for insulin labeling.

PMID- 24277610
TI  - Human and yeast DNA damage recognition complexes bind with high affinity DNA
      structures mimicking in size transcription bubble.
AB  - The human XPC-RAD23B complex and its yeast ortholog, Rad4-Rad23, are the primary
      initiators of global genome nucleotide excision repair. In this study, two types
      of DNA binding assays were used for the detailed analysis of interaction of these
      proteins with damaged DNA. An electrophoretic mobility shift assay revealed that
      human and yeast orthologs behave similarly in DNA binding. Quantitative analyses
      of XPC/Rad4 binding to the model DNA structures were performed using fluorescent
      depolarization measurements. The XPC-RAD23B and the Rad4-Rad23 proteins bind to
      the damaged 15 nt bubble-DNA structure mimicking in size the "transcription
      bubble" DNA intermediate with the highest affinity (KD values ~10(-10)  M or
      less) that is reduced in the following order: damaged bubble > undamaged bubble >
      damaged duplex > undamaged duplex. The affinity of XPC/Rad4 for various DNAs was
      shown to correlate with DNA bending angle. The results obtained show clearly that
      more deviation from regular DNA structure leads to higher XPC/Rad4 affinity.

PMID- 24277611
TI  - A green approach toward antibody purification: a sustainable biomimetic ligand
      for direct immobilization on (bio)polymeric supports.
AB  - This paper presents a sustainable strategy for improving the capture of
      antibodies by affinity chromatography. A novel biomimetic ligand (4-((4-chloro-6
      (3-hydroxyphenoxy)-1,3,5-triazin-2-yl)oxy)naphthalen-1-ol) (TPN-BM) was
      synthesized using a greener and simple protocol to overcome solubility
      limitations associated with ligand 22/8, known as artificial protein A.
      Furthermore, its subsequent immobilization on chitosan-based monoliths induced by
      plasma surface activation allowed the design of a fast and efficient
      chromatographic platform for immunoglobulin G (IgG) purification. The TPN-BM
      functionalized monoliths exhibited high-binding capacity (160 +/- 10 mg IgG per
      gram of support), and a selective capture of monoclonal antibodies directly from
      mammalian crude extracts in 85 +/- 5% yield and 98% of purity. The synthesis of
      ligand TPN-BM and the routes followed for monoliths preparation and
      functionalization were inspired in the green chemistry principles allowing the
      reduction of processing time, solvents and purification steps involved, turning
      the integrated system attractive from an economical and chemical point of view.

PMID- 24277612
TI  - Directly investigating the interaction between aptamers and thrombin by atomic
      force microscopy.
AB  - Aptamers are single-stranded nucleic acid molecules that can be used for protein
      recognition, detection, and inhibition. Over the past decades, two thrombin
      binding aptamers (15apt and 27apt) were reported by systemic evolution of ligands
      by exponential enrichment technique. Though many studies have been reported about
      the interactions between the aptamers and thrombin by atomic force microscopy,
      the thrombins in those studies were all immobilized by chemical agents. Recently,
      we developed a new method using atomic force microscopy to directly investigate
      the specific interactions between thrombin and its two aptamers without
      immobilizing the thrombin. Furthermore, the unbinding dynamics and dissociation
      energy landscapes of aptamer/thrombin were discussed. The results indicate that
      the underlying interaction mechanisms of thrombin with its two aptamers will be
      similar despite that the structures of 15apt and 27apt are different in buffer
      solution.

PMID- 24277614
TI  - Imaging material properties of biological samples with a force feedback
      microscope.
AB  - Mechanical properties of biological samples have been imaged with a force
      feedback microscope. Force, force gradient, and dissipation are measured
      simultaneously and quantitatively, merely knowing the atomic force microscopy
      cantilever spring constant. Our first results demonstrate that this robust method
      provides quantitative high resolution force measurements of the interaction. The
      small oscillation imposed on the cantilever and the small value of its stiffness
      result in vibrational energies much smaller than the thermal energy, reducing
      interaction with the sample to a minimum. We show that the observed mechanical
      properties of the sample depend on the force applied by the tip and consequently
      on the sample indentation.

PMID- 24277613
TI  - Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic
      function of human acetyl-CoA carboxylase 2.
AB  - Acetyl-CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative
      regulator of fatty acid beta-oxidation. Spot14, a thyroid hormone responsive
      protein, and Mig12, a Spot14 paralog, have recently been identified as regulators
      of fatty acid synthesis targeting ACC1, a distinctive subtype of ACC. Here, we
      examined whether Spot14/Mig12 modulates ACC2. Nanoscale protein topography mapped
      putative protein-protein interactions between purified human Spot14/Mig12 and
      ACC2, validated by functional assays. Human ACC2 displayed consistent enzymatic
      activity, and homogeneous particle distribution was probed by atomic force
      microscopy. Citrate-induced polymerization and enzymatic activity of ACC2 were
      restrained by the addition of the recombinant Spot14/Mig12 heterocomplex but only
      partially by the oligo-heterocomplex, demonstrating that the heterocomplex is a
      designated metabolic inhibitor of human ACC2. Moreover, Spot14/Mig12 demonstrated
      a sequestering role preventing an initial ACC2 nucleation step during filamentous
      polymer formation. Thus, the Spot14/Mig12 heterocomplex controls human ACC2
      polymerization and catalytic function, emerging as a previously unrecognized
      molecular regulator in catalytic lipid metabolism.

PMID- 24277615
TI  - Molecular arrangement between multivalent glycocluster and Pseudomonas aeruginosa
      LecA (PA-IL) by atomic force microscopy: influence of the glycocluster
      concentration.
AB  - New therapeutics strategy against cystic fibrosis seeks to prevent the adhesion
      of the bacterium Pseudomonas aeruginosa (PA) on the epithelial cells in the
      lungs. One of the factors that induces the adhesion is the interaction between
      natural glycocluster present on the cells and lectins such as the PA lectin LecA
      (PA-IL) present on the bacterium. By introducing synthetic glycoclusters with a
      great affinity with the lectin PA-IL, the adhesion can be prevented. In this
      study, we characterized, by atomic force microscopy, the interaction between a
      tetra-galactosylated glycocluster and the PA-IL lectin for high concentration of
      lectins (2.5 MUM).We showed that the strong lectin/lectin interaction is reduced
      even for low concentration of glycoclusters (1 for 20 000 lectins). We assumed
      that it is due to the tensioactive behavior of the glycoclusters. It was shown
      that the arrangement of the created complexes induced different structures
      evolving from one-dimensional elongated aggregates to two-dimensional compact
      islands when increasing the glycocluster concentration. This evolution can be
      interpreted as the predominance of the glycocluster/lectin interaction.

PMID- 24277616
TI  - Probing tethered targets of a single biomolecular complex with atomic force
      microscopy.
AB  - DNA origami shows tremendous promise as templates for the assembly of nano
      components and detection of molecular recognition events. So far, the method of
      choice for evaluating these structures has been atomic force microscopy (AFM), a
      powerful tool for imaging nanoscale objects. In most cases, tethered targets on
      DNA origami have proven to be highly effective samples for investigation. Still,
      while maximal assembly of the nanostructures might benefit from the greatest
      flexibility in the tether, AFM imaging requires a sufficient stability of the
      adsorbed components. The balance between the tether flexibility and sample
      stability is a major, poorly understood, concern in such studies. Here, we
      investigated the dependence of the tethering length on molecular capture events
      monitored by AFM. In our experiments, single biotin molecules were attached to
      DNA origami templates with various linker lengths of thymidine nucleotides, and
      their interaction with streptavidin was observed with AFM. Our results show that
      the streptavidin-biotin complexes are easily detected with short tethered
      lengths, and that their morphological features clearly change with the tethering
      length. We identify the functionally useful tether lengths for these
      investigations, which are also expected to prove useful in the construction and
      further application of DNA origami in bio-nanotechnology studies.

PMID- 24277618
TI  - HRAS mutations in epithelial-myoepithelial carcinoma.
AB  - The molecular profile of epithelial-myoepithelial carcinomas (EMCa) has not been
      well studied, though a recent association with Harvey rat sarcoma viral oncogene
      homolog (HRAS) mutations has been noted. To confirm and validate this, we
      surveyed fifteen EMCa for HRAS codon 61 mutations and correlated HRAS status with
      clinicopathologic parameters. There were 11 females and 4 males and mean patient
      age was 64 (range 49-90). Parotid gland was most commonly involved (n = 10) and
      the most common histologic appearance was that of a 'classic' EMCa (7/15). Four
      of fifteen (26.7 %) cases demonstrated local recurrence, while 2/15 (13.3 %)
      demonstrated distant metastases. Other variant morphologies included EMCa arising
      from pleomorphic adenoma (3/15), and high grade EMCa (2/15). HRAS exon 3, codon
      61 mutations, p.Q61R (n = 3) and p.Q61 K (n = 1) were identified in 4 of 15
      successfully tested EMCAs (14 patients). Two cases were classic type, while the
      other cases consisted of one oncocytic variant, and one tumor with myoepithelial
      overgrowth, the latter of which showed the same mutation in both the primary and
      recurrence. Of note, the high grade EMCa and EMCa ex pleomorphic adenoma were
      negative for mutations. Given the small number of cases, there were no
      significant differences between mutation positive and mutation negative cases in
      terms of age, gender and outcome. 

PMID- 24277620
TI  - Expression, glycosylation and secretion of phaseolin in a baculovirus system.
AB  - In this report, we describe the efficient expression and glycosylation, in insect
      cells, of beta-phaseolin polypeptides (M r 45 and 48 kDa) from Phaseolus
      vulgaris, by means of a baculovirus expression vector. N-terminal sequence
      analysis demonstrated that the signal peptide was efficiently processed.
      Tunicamycin treatment suppressed both phaseolin bands seen in untreated or
      control cells, and resulted in a single species (M r 43 kDa). We provide evidence
      that the observed size heterogeneity arises by asymmetric glycosylation of a
      single, high-molecular weight precursor. These results also indicate that
      differential glycosylation of phaseolin polypeptides can occur on the product of
      a single gene, and, in that sense, is not dependent on amino acid sequence
      variations. Phaseolin accumulates to a very high level (90 ug/10(6) cells), 90%
      of it being secreted into the culture medium. Immuno-gold staining and electron
      microscopy demonstrated phaseolin polypeptides in electron-dense, membrane-bound
      vesicles seen at the periphery of the cytoplasm of infect cells and in
      cytoplasmic multivesicular bodies. The effect on protein accumulation of a single
      basepair transversion (G"C) at position +6 is also described. This study
      constitutes, to our knowledge, one of the first instances of a plant protein
      being expressed in insect cells and suggests possible differences in the sorting
      mechanisms of glycoproteins from legume seeds and those from Spodoptera
      frugiperda cell line Sf9. 

PMID- 24277619
TI  - ALDH2 is associated to alcohol dependence and is the major genetic determinant of
      "daily maximum drinks" in a GWAS study of an isolated rural Chinese sample.
AB  - Alcohol dependence (AD) is a moderately heritable phenotype with a small number
      of known risk genes mapped via linkage or candidate gene studies. We considered
      313 males from among 595 members of documented, extended pedigrees in which AD
      segregates collected in Northern Hunan Province, China. A joint analysis of both
      males and females could not be performed as the difference in alcohol consumption
      variance was too large. Genome-wide association analyses were performed for
      approximately 300,000 single nucleotide polymorphisms (SNPs). Significant
      associations found in the ALDH2 region for AD (minimum P = 4.73 * 10(-8)) and two
      AD-related phenotypes: flushing response (minimum P = 4.75 * 10(-26)) and maximum
      drinks in a 24-hr period (minimum P = 1.54 * 10(-16)). Association of previous
      candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage
      disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response,
      AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%,
      7.9%, and 22.9% of phenotypic variation, respectively, in this sample. When rs671
      was considered as a candidate SNP in females, it explained 23.6% of the variation
      in flushing response, but alcohol consumption rates were too low among females
      despite familial enrichment for AD-for an adequate test of association for either
      AD or maximum drinks. These results support a mediating effect of aldehyde
      dehydrogenase deficiency on alcohol consumption in males and a secondary,
      culturally mediated limitation on alcohol consumption by females that should be
      appropriately modeled in future studies of alcohol consumption in populations
      where this may be a factor.

PMID- 24277621
TI  - On the mechanism of cytoplasmic male sterility in the 447 line of Vicia faba.
AB  - The trait of cytoplasmic male sterility, expressed in plants bearing the 447
      cytoplasm of Vicia faba, is uniquely and positively correlated with the presence
      of a linear double-stranded RNA molecule (dsRNA) 16.7 kb in size. Restriction
      enzyme digestion profiles of mitochondrial DNA isolated from fertile and
      cytoplasmic malesterile (CMS) lines do show a limited number of specific
      differences in fragment intensities and mobilities. However, mitochondria
      isolated from the progeny of the cross CMS * Restorer line contain DNA with an
      identical restriction profile as the male-sterile parent: moreover, subsequent
      generations are completely and permanently fertile, even upon segregation of the
      nuclear restoration gene. Southern hybridizations, using cDNA clones as probes,
      reveal homology between the CMS-associated dsRNA and the nuclear genome of both
      sterile and fertile lines. The regions cloned, representing approximately 22% of
      the total dsRNA sequence, show no homology to organelle DNA. We have not been
      able to stably transmit the dsRNA to fertile lines of V. faba or any other plant
      species, using a variety of standard virological techniques. 

PMID- 24277622
TI  - A common organization of the T-DNA genes expressed in plant hairy roots induced
      by different plasmids of Agrobacterium rhizogenes.
AB  - The recently described pathogenic plasmid from Agrobacterium rhizogenes 2659
      induces "hairy root" proliferation in infected plants which synthesize a new
      opine type, provisionally called cucumopine. The T-DNA restriction site map of
      2659 differs from other pRi T-DNAs, i.e., mannopine and agropine. However all
      these three different T-DNAs have a similar organization as detected through
      hybridization. This, previously shown by our cross-hybridization studies between
      mannopine and agropine pRi T-DNAs, is here extended to the cucumopine pRi T-DNA;
      each of the three pRi T-DNA is composed of successive DNA regions that would find
      actual counterparts in the two other T-DNAs. Equivalence of DNA regions is
      suggested by their similar length, location and organization in the three T-DNAs
      and by their sequence homology substantial enough to be reproducibly cross
      hybridized in all our experiments. This suggests that the three pRi T-DNAs share
      most of their functions. This was sought by analysing the pRi 2659 T-DNA gene
      expression in transformed plant tissues. The mRNA species observed in pRi 2659
      carrot hairy roots of in vitro cultures give a pattern that is rather unvariable
      and resembles those described for some agropine type pRi transformant tissues.
      This transcript pattern is consistent with the preservation in the pRi 2659 T-DNA
      of counterparts of most of the open reading frames detected in the TL-DNA of
      agropine type pRis. 

PMID- 24277623
TI  - Characterisation of a full-length cDNA clone for pea ferredoxin-NADP(+)
      reductase.
AB  - Ferredoxin-NADP(+) reductase has been purified to homogeneity from pea leaves and
      has been resolved into two forms by ion exchange chromatography and SDS gel
      electrophoresis. Antibodies to the proteins have been used to isolate pea leaf
      cDNA clones from a library in lambdagt11. A full-length clone of 1 400 bp encodes
      a polypeptide of 360 amino acid residues, of which 52 residues constitute an N
      terminal transit peptide and 308 residues make up the mature protein.
      Transcription and translation of the cDNA in vitro produces a protein of 40 kDa,
      which is imported by isolated pea chloroplasts and processed to the mature 34 kDa
      protein. Southern hybridisation to pea genomic DNA indicates that there are
      probably two genes in the haploid genome. 

PMID- 24277624
TI  - Molecular cloning of two isoinhibitor forms of chymotrypsin inhibitor 1 (CI-1)
      from barley endosperm and their expression in normal and mutant barleys.
AB  - Full-length cDNA clones for barley chymotrypsin inhibitor 1 (CI-1) have been
      isolated from an endosperm-specific cDNA library. Hybridization and nucleotide
      sequence analyses indicate that these cDNAs represent two distinct types of CI-1
      mRNA which we have called CI-1A and CI-1B. Both mRNAs encode polypeptides of 83
      residues (M r=8790 and 8960) which differ at eleven positions. The full-length
      cDNA sequences do not predict N-terminal signal peptide extensions indicating
      that CI-1 is synthesized in the mature form in contrast to the homologous
      proteinase inhibitors of tomato and potato. Northern hybridization experiments
      show that the CI-1 genes are under strict developmental and organ-specific
      control. CI-1 transcripts were first detected in the developing barley endosperm
      between 12 and 14 days after anthesis but no CI-1-related sequences were detected
      in the RNA preparations from shoots, leaves or roots. The expression of CI-1 was
      also studied in the high-lysine barley mutants Hiproly, Riso 56 and Riso 1508.
      Approximately 15-fold (Hiproly) and 4-fold (Riso 56 and 1508) higher levels of CI
      1 mRNA were detected in the mutant endosperms compared to normal barley. These
      results correlate well with the increased deposition of CI-1 in the high-lysine
      lines and show that the differential expression is controlled mainly at the level
      of transcription or stability of the mRNA. Using Southern-blots of barley DNA we
      estimate that there are three copies of CI-1 per haploid genome in both normal
      and mutant barley lines. 

PMID- 24277625
TI  - Plant gene expression during effective and ineffective nodule development of the
      tropical stem-nodulated legume Sesbania rostrata.
AB  - The expression of plant genes during symbiosis of Sesbania rostrata with
      Rhizobium sp. and Azorhizobium caulinodans was studied by comparing two
      dimensional PAGE patterns of in vitro translation products of poly(A)(+) RNA from
      uninfected roots and stems with that of root and stem nodules. Both types of
      nodules are essentially similar, particularly when stem nodules are formed in the
      dark. We detected the specific expression of at least 16 genes in stem and root
      nodules and observed the stimulated expression of about 10 other genes in both
      nodules. Six of the nodule-specific translation products (apparent molecular
      masses around 16 kDa) cross-react with an antiserum raised against leghemoglobin
      purified from Sesbania rostrata stem nodules. During stem nodule development,
      most of the nodule-stimulated genes are expressed concomitantly with
      leghemoglobin at day 12 after inoculation. However, some genes are already
      stimulated at days 6-7, some others later in development (day 18), and some are
      transiently activated. Patterns of root nodules induced by either Azorhizobium
      caulinodans strain ORS571, capable of effective root and stem nodulation, or
      Rhizobium sp. strain ORS51, capable of effective root nodulation only, are very
      similar except for a specific 37.5 kDa polypeptide. Several types of ineffective
      stem and root nodules were studied; in every case the amount of leghemoglobin
      components appeared reduced together with most of the nodule-stimulated
      polypeptides. 

PMID- 24277626
TI  - Patent injustice: how India brought cheap HIV drugs to Africa.

PMID- 24277627
TI  - Urgent care in England.

PMID- 24277628
TI  - beta blockers for adults with chronic obstructive pulmonary disease.

PMID- 24277629
TI  - Health act's troubled rollout hammers popular support.

PMID- 24277630
TI  - Indian academy recommends whole cell pertussis vaccine for primary vaccination.

PMID- 24277631
TI  - Sanitation campaigners call for urgent action over India's missing toilets.

PMID- 24277633
TI  - Prophylactic antibiotics for preventing Gram positive infections associated with
      long-term central venous catheters in oncology patients.
AB  - BACKGROUND: This is an updated version of the review which was first published in
      the Cochrane Database of Systematic Reviews in 2006. Long-term central venous
      catheters (CVCs), including tunnelled CVCs (TCVCs) and totally implanted devices
      or ports (TIDs), are increasingly used when treating oncology patients. Despite
      international guidelines on sterile insertion and appropriate CVC maintenance and
      use, infection remains a common complication. These infections are mainly caused
      by Gram positive bacteria. Antimicrobial prevention strategies aimed at these
      micro-organisms could potentially decrease the majority of CVC infections. The
      aim of this review was to evaluate the efficacy of antibiotics in the prevention
      of Gram positive infections in long-term CVCs. OBJECTIVES: To determine the
      efficacy of administering antibiotics prior to the insertion of long-term CVCs,
      or flushing or locking long-term CVCs with a combined antibiotic and heparin
      solution, or both, to prevent Gram positive catheter-related infections in adults
      and children receiving treatment for cancer. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (to June 2013) and the
      MEDLINE and EMBASE databases (1966 to 2013). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing prophylactic antibiotics given prior to long
      term CVC insertion with no antibiotics, RCTs comparing a combined antibiotic and
      heparin solution with a heparin-only solution to flush or lock newly inserted
      long-term CVCs, and RCTs comparing a combination of these interventions in adults
      and children receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected studies, classified them and extracted data on to
      a pre-designed data collection form. We pooled data using the RevMan software
      version 5.2 and used random-effects (RE) model methods for meta-analyses. MAIN
      RESULTS: We included 11 trials with a total of 828 oncology patients (adults and
      children). We assessed most included studies to be at a low or unclear risk of
      bias. Five trials compared the use of antibiotics (vancomycin, teicoplanin or
      ceftazidime) given before the insertion of the long-term CVC with no antibiotics,
      and six trials compared antibiotics (vancomycin, amikacin or taurolidine) and
      heparin with a heparin-only solution for flushing or locking the long-term CVC
      after use. Administering an antibiotic prior to insertion of the CVC did not
      significantly reduce Gram positive catheter-related sepsis (CRS) (five trials,
      360 adults; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.33 to 1.58; I2 =
      5 2%; P = 0.41).Flushing and locking long-term CVCs with a combined antibiotic
      and heparin solution significantly reduced the risk of Gram positive catheter
      related sepsis compared with a heparin-only solution (468 participants, mostly
      children; RR 0.47, 95% CI 0.28 to 0.80; I2 = 0%; P = 0.005). For a baseline
      infection rate of 15%, this reduction translated into a number needed to treat
      (NNT) of 12 (95% CI 9 to 33) to prevent one catheter-related infection. We
      considered this evidence to be of a moderate quality. AUTHORS' CONCLUSIONS: There
      was no benefit to administering antibiotics before the insertion of long-term
      CVCs to prevent Gram positive catheter-related infections. Flushing or locking
      long-term CVCs with a combined antibiotic and heparin solution appeared to reduce
      Gram positive catheter-related sepsis experienced in people at risk of
      neutropenia through chemotherapy or disease. Due to insufficient data it was not
      clear whether this applied equally to TCVCs and totally implanted devices (TIDs),
      or equally to adults and children. The use of a combined antibiotic and heparin
      solution may increase microbial antibiotic resistance, therefore it should be
      reserved for high risk people or where baseline CVC infection rates are high (>
      15%). Further research is needed to identify high risk groups most likely to
      benefit.

PMID- 24277634
TI  - [In Process Citation].

PMID- 24277632
TI  - Making connections: insulators organize eukaryotic chromosomes into independent
      cis-regulatory networks.
AB  - Insulators play a central role in subdividing the chromosome into a series of
      discrete topologically independent domains and in ensuring that enhancers and
      silencers contact their appropriate target genes. In this review we first discuss
      the general characteristics of insulator elements and their associated protein
      factors. A growing collection of insulator proteins have been identified
      including a family of proteins whose expression is developmentally regulated. We
      next consider several unexpected discoveries that require us to completely
      rethink how insulators function (and how they can best be assayed). These
      discoveries also require a reevaluation of how insulators might restrict or
      orchestrate (by preventing or promoting) interactions between regulatory elements
      and their target genes. We conclude by connecting these new insights into the
      mechanisms of insulator action to dynamic changes in the three-dimensional
      topology of the chromatin fiber and the generation of specific patterns of gene
      activity during development and differentiation. 

PMID- 24277635
TI  - Changes in noneconomic political attitudes of Southern and Northern youth, 1970s
      to 1980s.
AB  - This paper examines changes that occurred in the political attitudes of Southern
      and Northern youth from the 1970s to the 1980s. National survey data from the
      National Opinion Research Center is used. Considering attitudinal changes of
      people under 30, it appears that trends toward greater political tolerance and
      greater support for racial and sexual equality will continue in the future.
      However, this study finds a reversal of the usual trend of greater political
      tolerance among young people. The United States is increasing in conservatism on
      the social issues. Aside from the social issues, younger people have not become
      more conservative with age. Important regional differences in attitude changes
      are indicated. 

PMID- 24277636
TI  - Problem discovery, divergent thinking, and the creative process.
AB  - Previous empirical research suggests that problem discovery is an important step
      in the creative process. The present investigation was conducted to examine the
      role of problem discovery in the divergent thinking and creative performance of
      adolescents. Three divergent thinking tests were administered to a group of
      adolescents. Each test contained three presentedproblems and one
      discoveredproblem. The discovered problem allowed the adolescents to think of a
      problem and then to provide solutions. Comparisons indicated that the adolescents
      generated significantly more responses to the discovered problems than the
      presented problems. Most important was that the unique variance of the discovered
      problems (controlling the variance shared with scores from the presented
      problems) was reliable and significantly related to five indices of creative
      performance. These results support the componential theory of divergent thinking
      and creativity, and are consistent with the developmental view of problem
      finding. 

PMID- 24277637
TI  - The incidence of bulimic behavior in a secondary and University school
      population.
AB  - A survey questionnaire was instructor administered to high school and university
      students (n=1500) to assess the incidence of bulimic behavior. The questionnaire
      was tested and found to be a reliable and valid index for bulimic symptomatology.
      Respondents included 59% high school and 41% university level students. Data was
      evaluated by school, grade, sex, race, and interest area. Bulimic behavior was
      demonstrated at an incidence of 4.30% for the total sample. There was a
      nonsignificant higher incidence found in university (5.31%) compared to high
      school (3.98%) respondents. A significantly greater percentage of females
      responded with bulimic behavior than did males; however, there were no
      significant differences found between university and high school females. Bulimic
      behavior appeared to peak at Grades 11 and 13. Significantly more whites reported
      bulimic behavior than did blacks. Several academic interest areas not previously
      indicated in the literature may be more vulnerable to bulimic behavior. 

PMID- 24277638
TI  - Aggression and delinquency: Family and environmental factors.
AB  - Juvenile delinquency has become an increasing concern to society; aggressive
      behaviors are particularly harmful. This study examined parent and youth
      behaviors and personality types that may influence delinquent and aggressive
      behaviors. Youths were referred by the court to an intervention program; ratings
      of delinquency and aggression were derived from parent reports, self-reports, and
      court referral data. Results showed that high parent ratings of youth
      aggressiveness were related to high turmoil in the home and to youths' positive
      opinions of delinquent peers, while high aggressiveness of the youths' referring
      offenses was related to lax punishment. Developmentally, this suggests that in
      adolescence both the peer group and home influences are important in shaping
      different aspects of the youths' aggressive and delinquent behaviors. 

PMID- 24277639
TI  - Drinking behavior, drinking attitudes, and attachment relationship of
      adolescents.
AB  - In this article the connection between the drinking behavior and drinking
      attitudes of adolescents in relation to their attachment relationship with their
      parents is examined. The Family Episode Rating Task (FERT) was used, which was
      developed to measure the attachment relationship; it measures four patterns of
      parent-adolescent attachment. An Alcohol Questionnaire was used to measure the
      quantity and frequency of alcohol use, the amount of problem drinking, and the
      drinking attitudes of adolescents. It was hypothesized that anxiously attached
      adolescents have a greater risk of developing damaging drinking habits. One
      hundred sixty-one adolescents participated, all of them students in Grades 7, 9,
      and 11 of a high school. By means of an analysis of variance it was demonstrated
      that the Attitude scale's "drinking to facilitate social contact" was
      significantly related to the quality of the attachment relationship with the
      parents: this reason for drinking was mentioned most frequently among adolescents
      who were anxiously attached. 

PMID- 24277640
TI  - Adolescent fears: Some Caribbean findings.
AB  - A total of 657 adolescents (12-15 years) in Barbados provided responses to the
      question, "Is there anything you are really scared or afraid of?" Most frequently
      named fears were of three main types: fear of injury or death of self or loved
      ones, sexual concerns, and fears associated with school failure. However, certain
      other fears usually reported as relatively infrequent among adolescents in
      industrialized countries, such as fear of the dark, fear of walking lonely roads,
      and fear of animals, were also prominent, and reflect local geographical and
      cultural conditions. The influence of the media was also evident: many students
      were concerned about nuclear war, or held somewhat exaggerated fear of certain
      threats to personal safety (for example, being killed) given actual local
      incidence levels. From a guidance and counseling perspective, the data
      particularly highlight the need for improved sex and family life education. 

PMID- 24277641
TI  - Photoinduced atom transfer radical polymerization using semiconductor
      nanoparticles.
AB  - Photoinduced atom transfer radical polymerization of methyl methacrylate
      initiated by in situ generation of copper (I) complex from higher oxidation state
      species using neat zinc oxide and iron-doped zinc oxide nanoparticles is
      investigated. The polymerizations proceed in a well-controlled manner under UV
      light at room temperature as evidenced by kinetic and light on-off experiments.
      The evolution of molecular weight with conversion shows good correlations between
      experimental and theoretical molecular weights, which confirmed good control over
      polymerization along with a narrow molecular weight distribution. 

PMID- 24277642
TI  - Ultra-performance liquid chromatography coupled with electrospray
      ionization/quadrupole time-of-flight mass spectrometry for the rapid analysis of
      constituents in the traditional Chinese medical formula Danggui San.
AB  - In this work, ultra-performance LC with ESI quadrupole TOF-MS (UPLC-ESI-Q-TOF-MS)
      and automated MetaboLynx analysis was used to rapidly separate and identify the
      chemical constituents of Danggui San, a traditional Chinese medical formula. The
      analysis was performed on a Waters UPLC BEH C18 column using a gradient elution
      system. A hyphenated ESI and Q-TOF analyzer was used for the determination of the
      accurate mass of the protonated or deprotonated molecule and fragment ions in
      both positive and negative modes. Based on retention times, accurate mass, and
      the mass spectrometric fragmentation characteristics, a total of 47 compounds
      distributed over the chemical groups of phthalides, flavonoids, monoterpene
      glycosides, sesquiterpenoids, phenolics, and alkaloids, were simultaneously
      separated within 18 min and identified or tentatively elucidated in Danggui San
      for the first time. UPLC-ESI-Q-TOF-MS analysis revealed the complexity of the
      chemical composition of this formula. The method developed is rapid, accurate,
      reliable, and highly sensitive to characterize the chemical constituents of
      Danggui San. 

PMID- 24277643
TI  - DNA methylation reprogramming in cancer: does it act by re-configuring the
      binding landscape of Polycomb repressive complexes?
AB  - DNA methylation is a repressive epigenetic mark vital for normal development.
      Recent studies have uncovered an unexpected role for the DNA methylome in
      ensuring the correct targeting of the Polycomb repressive complexes throughout
      the genome. Here, we discuss the implications of these findings for cancer, where
      DNA methylation patterns are widely reprogrammed. We speculate that cancer
      associated reprogramming of the DNA methylome leads to an altered Polycomb
      binding landscape, influencing gene expression by multiple modes. As the Polycomb
      system is responsible for the regulation of genes with key roles in cell fate
      decisions and cell cycle regulation, DNA methylation induced Polycomb mis
      targeting could directly drive carcinogenesis and disease progression.

PMID- 24277645
TI  - Follow-up protocols for women with cervical cancer after primary treatment.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women up to 65
      years of age and is the most frequent cause of death from gynaecological cancers
      worldwide. Although surveillance of women after completion of primary treatment
      for cervical cancer is purported to have an impact on their overall survival
      (OS), no strictly defined follow-up protocols are available for these women. Wide
      diversity in management has been noted in the follow-up of women who have
      completed primary treatment for cervical cancer. Traditionally, women treated for
      cervical cancer undergo routine long-term, even life-long, follow-up. The primary
      objective of this practice has been to detect and treat recurrence early. This
      review sets out to systematically evaluate available evidence for the role of
      different models of follow-up after cervical cancer and the optimal use of
      investigations. OBJECTIVES: To evaluate the benefits, harms and costs of
      different follow-up protocols for women who have completed primary treatment for
      cervical cancer. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2013,
      Issue 1), the Cochrane Gynaecological Cancer Group (CGCG) Trials Register,
      MEDLINE and EMBASE up to January 2013. We also searched registers of clinical
      trials, abstracts of scientific meetings and reference lists of clinical
      guidelines and review articles and contacted experts in the field. SELECTION
      CRITERIA: We searched for randomised controlled trials (RCTs) that compared
      different follow-up protocols after primary treatment in women with cervical
      cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      whether potentially relevant studies met the inclusion criteria. No trials were
      found, and therefore no data were analysed. MAIN RESULTS: The search strategy
      identified 1,377 unique references, of which all were excluded on the basis of
      title and abstract. AUTHORS' CONCLUSIONS: We found no evidence to inform
      decisions about different follow-up protocols after primary treatment for women
      with cervical cancer. Ideally, a large RCT or, at the very least, well-designed
      non-randomised studies (NRSs) that use multi-variate analysis to adjust for
      baseline imbalances are needed to compare these follow-up protocols. Such studies
      could include prospective trials conducted to determine the benefits and harms of
      different follow-up protocols upon completion of primary treatment for cervical
      cancer, along with an RCT undertaken to compare predefined follow-up protocols
      versus participant-initiated follow-up versus no follow-up until a participant is
      referred to a gynaecological oncology service after signs or symptoms of
      recurrence have been identified in the primary care or community setting.

PMID- 24277644
TI  - Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects.
AB  - BACKGROUND: Activated charcoal is commonly used to manage overdose or accidental
      ingestion of medicines. This study evaluated the effect of activated charcoal on
      apixaban exposure in human subjects. METHODS: This was an open-label, three
      treatment, three-period, randomized, crossover study of single-dose apixaban (20
      mg) administered alone and with activated charcoal given at 2 or 6 h post-dose to
      healthy subjects. Blood samples for assay of plasma apixaban concentration were
      collected up to 72 h post-dose. Pharmacokinetic parameters, including peak plasma
      concentration (Cmax), time to Cmax (Tmax), area under the concentration-time
      curve from time 0 to infinity (AUCINF), and terminal half-life (T1/2), were
      derived from apixaban plasma concentration-time data. A general linear mixed
      effect model analysis of Cmax and AUCINF was performed to estimate the effect of
      activated charcoal on apixaban exposure. RESULTS: A total of 18 subjects were
      treated and completed the study. AUCINF for apixaban without activated charcoal
      decreased by 50 and 28%, respectively, when charcoal was administered at 2 and 6
      h post-dose. Apixaban Cmax and Tmax were similar across treatments. The mean T1/2
      for apixaban alone (13.4 h) decreased to ~5 h when activated charcoal was
      administered at 2 or 6 h post-dose. Overall, apixaban was well tolerated in this
      healthy population, and most adverse events were consistent with the known
      profile of activated charcoal. CONCLUSION: Administration of activated charcoal
      up to 6 h after apixaban reduced apixaban exposure and facilitated the
      elimination of apixaban. These results suggest that activated charcoal may be
      useful in the management of apixaban overdose or accidental ingestion.

PMID- 24277646
TI  - A retrospective cohort study of mode of delivery among public and private
      patients in an integrated maternity hospital setting.
AB  - OBJECTIVE: To examine the associations between mode of delivery and public versus
      privately funded obstetric care within the same hospital setting. DESIGN:
      Retrospective cohort study. SETTING: Urban maternity hospital in Ireland.
      POPULATION: A total of 30 053 women with singleton pregnancies who delivered
      between 2008 and 2011. METHODS: The study population was divided into those who
      booked for obstetric care within the public (n=24 574) or private clinics
      (n=5479). Logistic regression analyses were performed to examine the associations
      between operative delivery and type of care, adjusting for potential confounding
      factors. MAIN OUTCOME MEASURES: Caesarean section (scheduled or emergency),
      operative vaginal delivery (vacuum or forceps), indication for caesarean section
      as classified by the operator. RESULTS: Compared with public patients, private
      patients were more likely to be delivered by caesarean section (34.4% vs 22.5%,
      OR 1.81; 95% CI 1.70 to 1.93) or operative vaginal delivery (20.1% vs 16.5%, OR
      1.28; 95% CI 1.19 to 1.38). The greatest disparity was for scheduled caesarean
      sections; differences persisted for nulliparous and parous women after
      controlling for medical and social differences between the groups (nulliparous
      11.9% vs 4.6%, adjusted (adj) OR 1.82; 95% CI 1.49 to 2.24 and parous 26% vs
      12.2%, adj OR 2.08; 95% CI 1.86 to 2.32). Scheduled repeat caesarean section
      accounted for most of the disparity among parous patients. Maternal request per
      se was an uncommonly reported indication for caesarean section (35 in each group,
      p<0.000). CONCLUSIONS: Privately funded obstetric care is associated with higher
      rates of operative deliveries that are not fully accounted for by medical or
      obstetric risk differences.

PMID- 24277647
TI  - The high school "Junior Theme" as an adolescent rite of passage.
AB  - This paper examines high school research projects as an adolescent transitional
      episode that demarks acquisition of a capacity for prolonged creative effort.
      Whereas tests of courage are important in many subsistence societies, in ours a
      valued quality of adulthood is the ability to think and act on one's own. Self
      report data from 154 students working on a "Junior Theme" are employed to
      illustrate the psychological significance of this kind of "rite." The students
      report a range of emotional states that are well out of their normal school
      experience. Many go through a process of personal involvement and self-searching
      that resembles an identity quest. As a result of the project students feel they
      have acquired a new status, one that separates them from the uninitiated and puts
      them closer to the status and power of an autonomous adult. 

PMID- 24277648
TI  - Storm and stress beliefs about adolescence: Prevalence, self-reported
      antecedents, and effects of an undergraduate course.
AB  - The purpose of the present study was to determine the prevalence and self
      reported developmental antecedents of beliefs in storm and stress notions about
      adolescence, and to investigate the effects on such beliefs of an undergraduate
      course on adolescent development. Subjects were 192 college students who were
      enrolled in a course entitled "Psychology of Adolescence" at a large urban
      university. The questionnaire, which was administered at the beginning and end of
      the course, contained a storm and stress scale, items tapping the nature of
      parent-adolescent arguments, Dusek and Flaherty's (1981) Self-Concept Scale, and
      several demographic questions. Results suggested that beliefs in storm and stress
      notions are quite prevalent, arguments between parents and adolescents are
      believed to occur quite frequently, and females endorse storm and stress beliefs
      more readily than do males. Moreover, subjects tended to endorse storm and stress
      notions more readily if they viewed themselves as being less adjusted during
      their own adolescence and if they reported more adjustment instability. After a
      course on adolescent development, the tendency to report that the typical
      adolescent experiences storm and stress decreased, and this decrease was more
      pronounced for those receiving higher grades in the course. 

PMID- 24277649
TI  - Social support and self-esteem in adolescence.
AB  - This study assessed contingencies in the effect of social support from parents
      and friends on adolescent self-esteem. Questionnaires were administered to 76
      Israeli adolescents regarding self-esteem, stressful life events, and perceived
      level of support from mother, father, and friends. Maternal support had a strong
      effect on self-esteem. Aid from friends was influential primarily when that of
      mothers was absent. Paternal support had little effect, once other support
      sources were controlled. Despite the negative influence of stress on self-esteem,
      support and stress had no interactive effects. These findings, consistent with
      attachment theory and social provision theories, were contrary to cross-pressure
      or separate world models of peer/parent influence. 

PMID- 24277650
TI  - Recognition accuracy, stereotypic preference, aversion, and subjective judgment
      of body appearance in adolescents and young adults.
AB  - Accuracy of body image, stereotypic preference, and aversion to body types were
      investigated in two studies. Using line drawings of 19 somatotypes in three
      orientations, 160 subjects in four age groups selected preferred, least
      preferred, and self-estimates of their own body types. Five independent ratings
      were made by judges of the subjects' body type. Females underestimated and males
      tended to overestimate their body dimensions. Both sexes overwhelmingly chose the
      endomorph as the least preferred somatotype. The consensus among females was to
      prefer slim figures and among males to prefer a medium muscular physique. In the
      second study three aspects of body image were studied by adjusting one's image on
      a television monitor that displayed a whole continuum of self-images from
      ectomorphy to endomorphy. Subjective body images were found to lie between the
      objective somatotype and the ideal. 

PMID- 24277651
TI  - Indicators of rural youth drug use.
AB  - The relationships between personal substance use, health beliefs, peer use, sex,
      and religion were examined using data collected from 265 middle school students
      in rural northern Michigan and northeastern Wisconsin in January and February
      1984. A positive correlation between peer and personal drug use was established.
      A relationship was also found between health beliefs and personal substance use.
      In addition, a regression model was able to account for a statistically
      significant amount of the variance of alcohol, marihuana, and cigarette use in
      the target population. Recommendations are made concerning future research,
      methods of improving health education program development, and possible target
      areas for psychotherapy. 

PMID- 24277652
TI  - Stages of identity development and problem drinking in college women.
AB  - Deviation from age-appropriate identity-developmental stage and problem drinking
      in 75 undergraduate women was investigated. A quantity/frequency scale assessed
      problem drinking. Two measures of identity, one projective and one observational,
      were used. May's Deprivation/Enhancement fantasy pattern measure assessed sexual
      identity. The College Women's Assertion Sample assessed the cognitive-style
      component of identity. The results supported the hypotheses that younger
      (freshman/sophomore) women deviating from their age-appropriate identity stage of
      dedifferentiation, and older (junior/senior) women deviating from their age
      appropriate stage of identity integration, were significantly more likely to
      experience drinking problems than were women who had entered their age
      appropriate identity stages. The findings support psychodynamic theories of
      identity development in late adolescence, and suggest that problem-drinking women
      in different age/ developmental stages of identity drink for different reasons
      and should be treated differently. 

PMID- 24277653
TI  - Separation-individuation and ego identity status in late adolescence: A two-year
      longitudinal study.

PMID- 24277654
TI  - Statin therapy in heart failure: for good, for bad, or indifferent?
AB  - Statins are effective in the prevention of coronary events and the treatment of
      acute coronary syndromes. However, their efficacy and safety in patients with
      heart failure (HF) is still a matter of debate. On the basis of literature
      evidence from subgroup analysis, retrospective, prospective cohort studies, and
      randomized controlled trials, in this review we try to answer the following
      question: Is statin therapy in HF patients for good, for bad, or indifferent?
      Some studies showed a negative impact of low cholesterol levels in patients with
      severe HF (endotoxin-lipoprotein hypothesis and coenzyme Q10 hypothesis). On the
      other hand, a large amount of literature demonstrates that in patients with HF,
      statins have a positive impact on survival and other outcomes, regardless of
      whether the HF was of ischemic or nonischemic origin, which is related to a
      combination of mechanisms (pleiotropic effects and cholesterol reduction). Much
      of this evidence, however, comes from observational and retrospective studies and
      subgroup analyses of statin use in patients with HF. Randomized clinical trials
      examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a
      benefit in mortality for patients with HF randomized to receive statins.
      Nevertheless, a meta-analysis found that statin therapy does not decrease all
      cause or cardiovascular mortality but significantly decreases the rate of
      hospitalization for worsening HF and increased left ventricular ejection fraction
      compared with placebo. 

PMID- 24277656
TI  - The architecture of diagnostic research: from bench to bedside--research
      guidelines using liver stiffness as an example.
AB  - The diagnostic research process can be divided into five phases, designed to
      establish the clinical utility of a new diagnostic test--the index test. The aim
      of the present review is to illustrate the study designs that are appropriate for
      each diagnostic phase, using clinical examples regarding liver fibrosis diagnosed
      with transient elastography, when possible. Phase 0 is the preclinical pilot
      phase during which the validity, reliability, and reproducibility of the index
      test are assessed in healthy and diseased people. Phase I is designed to describe
      the distribution of the index test results in healthy people and its normal
      values. Phase IIA comprises studies designed to estimate the accuracy
      (sensitivity and specificity) of the index test in discriminating between
      diseased and nondiseased people in a clinically relevant population. Phase IIB
      studies allow the comparison of the accuracy of different index tests; Phase IIC
      studies aim to evaluate the possible harms of incorporating the index test in a
      diagnostic-therapeutic strategy. In phase III, diagnostic test-therapeutic
      randomized clinical trials aim to assess the benefits and harms of the new
      diagnostic-therapeutic strategy versus the present strategy. Phase IV comprises
      large surveillance cohort studies that aim to assess the effectiveness of the new
      diagnostic-therapeutic strategy in clinical practice. CONCLUSION: As common in
      clinical research, giving excessive weight to the results of single studies and
      trials is likely to divert from the totality of evidence obtained through the
      systematic reviews of these studies, conducted with rigorous methodology and
      statistical methods. (Hepatology 2014;60:408-418).

PMID- 24277655
TI  - Are there any benefits from statin treatment for the septic patient?
AB  - Statins have become the most widely used drugs for lowering cholesterol levels
      worldwide. At least 20% of patients requiring admission to hospital are on
      established statin therapy, and this proportion is growing each year. Evidence
      from observational studies and basic science research suggests that statins might
      be associated with a reduced mortality in sepsis. Randomized trials are producing
      equivocal results but have not shown the marked improvement in outcome suggested
      by the observational studies. Continued use in current statin users appears a
      more fruitful area for future research than statin use de novo as an adjuvant
      therapy in sepsis. Statin use in patients with pneumonia, acute lung injury or
      early sepsis warrants further study. International practice of statin use in
      critically ill patients is variable, and potential toxicity mandates careful
      monitoring. Further studies are required to address fundamental issues such as
      efficacy, potential target patient populations, dose, class equivalence and
      safety.

PMID- 24277657
TI  - Volume criteria for the treatment of head and neck cancer: Are they evidence
      based?

PMID- 24277658
TI  - Focal 18F-FDG uptake in bone marrow on PET/CT in a patient with JAK2 mutation
      without overt myeloproliferative neoplasm.

PMID- 24277660
TI  - Volume-targeted ventilation is more suitable than pressure-limited ventilation
      for preterm infants: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effect of volume-targeted ventilation (VTV) compared
      with pressure-limited ventilation (PLV) in preterm infants. METHOD: We searched
      the Cochrane Library (Issue 3, 2013), PubMed (1966 to 5 March 2013), China
      National Knowledge Infrastructure (CNKI) and periodical databases (1979 to 5
      March 2013). We selected randomised controlled trials (RCTs) and quasi-RCTs of
      VTV versus PLV as active interventions in preterm infants. We performed meta
      analyses using the Cochrane statistical package RevMan 5.0. RESULTS: Eighteen
      trials met our inclusion criteria. There was no evidence that VTV modes reduced
      the incidence of death (relative risk (RR) 0.73, 95% CI 0.51 to 1.05). The use of
      VTV modes resulted in a reduction in the incidence of bronchopulmonary dysplasia
      (BPD) (RR 0.61, 95% CI 0.46 to 0.82) and duration of mechanical ventilation (mean
      difference (MD) -2.0 days, 95% CI -3.14 to -0.86). VTV modes also resulted in
      reductions in intraventricular haemorrhage (IVH) (RR 0.65, 95% CI 0.42 to 0.99),
      grade 3/4 IVH (RR 0.55, 95% CI 0.39 to 0.79), periventricular leukomalacia (PVL)
      (RR 0.33, 95% CI 0.15 to 0.72), pneumothorax (RR 0.52, 95% CI 0.29 to 0.93),
      failure of primary mode of ventilation (RR 0.64, 95% CI 0.43 to 0.94), hypocarbia
      (RR 0.56, 95% CI 0.33 to 0.96), mean airway pressure (MD -0.54 cmH2O, 95% CI 
      1.05 to -0.02) and days of supplemental oxygen administration (MD -1.68 days, 95%
      CI -2.47 to -0.88). CONCLUSIONS: Preterm infants ventilated using VTV modes had
      reduced duration of mechanical ventilation, incidence of BPD, failure of primary
      mode of ventilation, hypocarbia, grade 3/4 IVH, pneumothorax and PVL compared
      with preterm infants ventilated using PLV modes. There was no evidence that
      infants ventilated with VTV modes had reduced death compared to infants
      ventilated using PLV modes.

PMID- 24277659
TI  - JAK2V617F allele burden is associated with thrombotic mechanisms activation in
      polycythemia vera and essential thrombocythemia patients.
AB  - The clinical courses of polycythemia vera (PV) and essential thrombocythemia (ET)
      are characterized by thrombohemorrhagic diathesis. Several groups have suggested
      an association between JAK2V617F mutation and thrombosis. We hypothesized a
      relationship between JAK2V617F allele burden, cellular activation parameters, and
      thrombosis. We evaluated a group of PV and ET patients using flow cytometry:
      platelet CD62P, CD63, and dense granules, platelet-leukocyte aggregates (PLA),
      leukocyte CD11b and monocyte tissue factor (TF) expression. All patients had
      increased baseline platelet CD62P and CD63 expression (p < 0.05); 71 % of PV and
      47 % of ET presented with a storage pool disease. Leukocyte CD11b, TF, and PLA
      were elevated in all patients. TF was higher in PV compared to ET (p < 0.05) and
      platelet-neutrophil [polymorphonuclear (PMN)] aggregates were increased in ET
      versus PV (p < 0.05). In ET, PLA were correlated with platelet numbers (p <
      0.05). In all patients, JAK2V617F allele burden was directly correlated with
      monocyte CD11b. Patients with JAK2V617F allele burden >50 % presented higher
      levels of leukocyte activation. In ET, thrombosis was associated with JAK2V617F
      mutation (p < 0.05, chi (2) = 5.2), increased monocyte CD11b (p < 0.05) and with
      platelet-PMN aggregates (p < 0.05). In ET patients, hydroxyurea does not
      significantly reduce the activation parameters. Our data demonstrate that
      JAK2V617F allele burden is directly correlated with activation parameters that
      drive mechanisms that favor thrombosis.

PMID- 24277661
TI  - Compliance with the Baby-Friendly Hospital Initiative and impact on breastfeeding
      rates.
AB  - OBJECTIVES: To examine compliance with the Baby-Friendly Hospital Initiative
      (BFHI) as well as evaluate the BFHI and its components on breastfeeding
      initiation and duration overall and according to maternal education level.
      DESIGN: Quasi-experimental study using data from the Pregnancy Risk Assessment
      Monitoring System (PRAMS) from 2004 to 2008. SETTING: Birth facilities in Maine.
      PARTICIPANTS: 915 mothers who gave birth in four hospitals that were BFHI
      accredited or became accredited and 1099 mothers from six matched non-BFHI
      facilities. Mothers reported on seven (of 10) BFHI practices (breastfeeding
      practice score 0-7) and receipt of a gift pack with formula (yes/no). MAIN
      OUTCOME MEASURES: Self-report of breastfeeding initiation, any breast feeding for
      >=4 weeks, exclusive breast feeding for >=4 weeks. RESULTS: 34.6% of mothers from
      BFHI-accredited facilities reported experiencing all seven BFHI breastfeeding
      practices, while 28.4% reported being given a gift pack with formula. Among
      mothers with lower education, the BFHI increased breastfeeding initiation by 8.6
      percentage points (adjusted coefficient, 0.086 [95% CI, 0.01 to 0.16]) and,
      independently, each additional breastfeeding practice was associated with an
      average increase in breastfeeding initiation of 16.2 percentage points (adjusted
      coefficient, 0.162 [95% CI, 0.15 to 0.18]). Among all mothers and mothers with
      higher education, there was no effect of the BFHI on breastfeeding rates.
      CONCLUSIONS: Compliance with BFHI practices among BFHI-accredited facilities is
      not optimal and needs to be monitored, as greater compliance may have an even
      larger impact on breastfeeding rates and potentially reduce socio-economic
      disparities in breast feeding.

PMID- 24277662
TI  - The long-term psychosocial outcomes following excision of sacrococcygeal
      teratoma: a national study.
AB  - OBJECTIVE: The overall effect of the reported long-term sequelae following
      sacrococcygeal teratoma (SCT) excision on the psychosocial and sexual development
      has not been addressed appropriately in the literature. The aim of this study was
      to evaluate the psychosocial adjustment of a national cohort of SCT patients
      using a validated psychosocial questionnaire. METHODS: Three paediatric surgery
      centres in Scotland were contacted to identify those SCT patients who were now 5
      years or older. The main outcome measure was the Derriford Appearance Scale 59
      (DAS-59) which assesses concerns of everyday living, personal relationships, self
      esteem and emotional distress. Following ethical approval, age appropriate
      invitation letters and information sheets for both parents and patients were sent
      to prospective participants. Parents/patients were contacted after 2 weeks to
      arrange an interview to complete the questionnaire. RESULTS: 31/48 (65%) of
      patients identified with SCT completed the DAS-59. Participant ages ranged from 5
      to 35 years (median 12 years). 5/31 (16%) were malignant cases. There were 25
      (81%) female participants and 12 (39%) patients older than 16 years. 9/31 (29%)
      participants indicated concern over their appearance. However, we found low
      levels of appearance-related distress and overall participants showed positive
      adjustment to personal relationships and everyday living on the DAS-59.
      CONCLUSIONS: This is the first study looking at the psychosocial adjustment of
      patients with SCT using a validated psychosocial questionnaire. Encouragingly, we
      found low levels of appearance-related distress. Future research could identify
      those factors associated with increased risk of poorer outcomes and highlight
      those in need of psychological intervention.

PMID- 24277663
TI  - WITHDRAWN: Single dose dipyrone for acute postoperative pain.

PMID- 24277664
TI  - Establishment of mice with inheritable susceptibility to productive hepatitis C
      virus infection.

PMID- 24277665
TI  - Adolescent autonomy and parental stress.
AB  - The present investigation explores the relationship between adolescent autonomy
      and parental stress among families with children aged 10-17. Independent measures
      were obtained from parents and children. Parents of early adolescent children
      reported significantly more stress than parents of preadolescents or middle
      adolescents. Parents of first-born children reported significantly more stress
      than did more experienced parents. Although mothers and fathers reported
      comparable levels of overall parental stress, their stress was, in part, the
      result of different factors. Fathers reported higher levels of stress if their
      children reported not following their advice and being involved in deviant
      activities. For mothers, stress was significantly related to their children's
      desire for greater autonomy. Emotional detachment was not a significant predictor
      of parental stress for either mothers or fathers. Implications of the findings
      for the parent-child relationship during adolescence are discussed. 

PMID- 24277666
TI  - The relation of personality functions and adaptive skills to self-esteem in early
      adolescence.
AB  - This paper examines the relation, in early adolescence, of competence in
      personality functions and adaptive skills to self-esteem. As part of a
      longitudinal study of adolescent personality development, a nonclinical group of
      63 adolescents underwent a comprehensive assessment at age 13. Their personality
      functioning status was assessed by means of a semistructured psychiatric
      interview. A psychometric battery was administered to assess verbal and nonverbal
      adaptive skills. In addition, global self-esteem was assessed. The findings
      indicate that positive self-esteem was associated with competence in both
      personality functions and in adaptive skills. Both domains contributed to self
      esteem to a similar degree. 

PMID- 24277667
TI  - The role of reciprocity and proximity in junior high school friendships.
AB  - The relationship of reciprocity, sex, and race to friendship proximity in
      adolescent friendships was studied. Intelligence, personality, physical
      attractiveness, popularity, and proximity were measured for 136 junior high
      school students. Subjects were classified as either having reciprocated or
      nonreciprocated friendships. Reciprocated adolescents were perceived as more
      attractive, had higher social status, and were more committed to their best
      friend than nonreciprocated adolescents. More black than white students were in
      the nonreciprocated group. White students had more in-school contact and black
      students more out-of-school contact with their friends. 

PMID- 24277668
TI  - Delinquent behaviors and male adolescent development: A preliminary study.
AB  - Commonly identified developmental tasks of male adolescence were examined for
      their relationship to delinquent behavior during adolescence among a general
      sample of 11-to 18-year-old males (N=337). Evaluations of the prevalence and mean
      level of delinquent acts across the age groups confirms previous suggestions that
      delinquent behavior follows the adolescent years quite closely. Measures of three
      primary developmental domains-family relations, social relations, and
      educational/vocational orientations-were taken and correlated with delinquent
      behavior across three substages of adolescence. The patterns of correlations
      suggest there is support for the view that a substantial portion of delinquent
      behavior is tied to struggles with adolescent development tasks. 

PMID- 24277669
TI  - Family interaction patterns and the development of social conceptions in the
      adolescent.
AB  - The relationship between family interaction and the formation of family and life
      conceptions in adolescence was studied in an interactional framework. It was
      hypothesized that openness and constructiveness in family communication and the
      expression of marital conflicts are positively related to number and content of
      family and life conceptions. A sex difference was also hypothesized for these
      conceptions. Fifty-three 15-year-old girls and boys participated in the study.
      They were interviewed individually and afterward presented with a questionnaire
      on their family ratings. In addition, most parents-40 mothers and 30 fathers
      answered their own questionnaires. The ratings of family interaction by
      adolescents and parents, respectively, correlated positively, indicating the
      reliability of the adolescents' ratings. The hypotheses were supported by the
      results. The richness of family-centered communication and the open expression of
      marital conflicts together with a positive emotional atmosphere were crucial to
      the number and content of the adolescents' social conceptions, especially family
      conceptions. 

PMID- 24277670
TI  - Achievement of autonomy by nonhandicapped and mildly learning handicapped
      adolescents.
AB  - This study examines the achievement of autonomy by a sample of 30 midly learning
      handicapped and 30 nonhandicapped adolescents. From participant observation over
      the course of a school year, a detailed account was obtained about the life of
      each subject, both in the home and among friends outside the home. Findings
      suggest that autonomy is achieved through a gradual process of negotiation during
      the high school years. The mildly handicapped adolescents generally lag behind
      their regular education counterparts in breaking away from the family. While
      almost three-fourths of the nonhandicapped sample had made significant gains
      toward increased freedom, less than half of the mildly handicapped sample had
      shed close supervision by parents. However, most of the handicapped adolescents
      were satisfied with the limited freedom they had. The data suggest that autonomy
      should be understood as relative to the needs and abilities of each individual.
      Not all adolescents develop at the same pace; not all feel the same desire to
      assert their independence from their parents when they reach a particular age. 

PMID- 24277672
TI  - Diabetes and hyperglycemia in the critical care setting: has the evidence for
      glycemic control vanished? (Or ... is going away?).
AB  - Hyperglycemia is associated with increased mortality and other complications
      amongst hospitalized patients. However, the studies of tight glycemic control in
      a range of critical illness settings, including intensive care, acute myocardial
      infarction, and stroke, have produced inconsistent and divergent results. We
      examine some of the factors that may have contributed to the differing results,
      and their implications for targeting tight glucose control in critical illness.
      With these in mind, most clinical guidelines now recommend moderate glucose
      control with an upper glucose target of <10 mmol/L (180 mg/dL) in critical
      illness while avoiding hypoglycemia.

PMID- 24277673
TI  - Changing epidemiology of metabolic syndrome and type 2 diabetes in Chinese youth.
AB  - China is gradually taking its place as one of the world's economic giants and
      concurrently learning to understand how to bear the burdens of diseases that are
      more common in the fully developed world, such as pediatric obesity, metabolic
      syndrome, and type 2 diabetes mellitus. The purpose of this review is to
      consolidate the available information regarding these and draw the focus toward
      their sequential progression and increasing prevalence in Chinese children.
      Studies were collected in both English and Chinese, and the data were reviewed on
      the basis of disease prevalence and risk factors that are known from scientific
      literature that has been published to date. The majority of studies with
      appropriate content for inclusion here have been conducted within the last 15
      years and up to date information from recent local and international research has
      also been included. Several factors have been implicated for the rise in obesity,
      most notably, the progressing economic expansion and exposure of local Chinese
      populations to Western influences. With this, metabolic syndrome has become a
      growing concern, as it is a precursor to cardiovascular disease and type 2
      diabetes, leading to the alarmingly rapid development of deleterious consequences
      in children. The International Diabetes Federation proposed a definition for
      metabolic syndrome in 2007 (MS-IDF2007) worldwide, but whether it is also
      suitable for the Chinese population remains uncertain, so we have created the
      Chinese definition of metabolic syndrome upon the IDF framework. This MS-CHN2012
      definition is based on multicenter studies to simplify and standardize primary
      care screening methods and is the first of its kind in China. Juvenile type 2
      diabetes is the most worrisome result of obesity and metabolic syndrome, and
      studies have shown that the prevalence has doubled within 5 years-surpassing the
      prevalence of juvenile type 1 diabetes. Because of the extremely low number of
      studies currently published on these topics in China, emphasis needs to be placed
      on the assessment of the health status of the population. Screening methods are
      imperative because lifestyle interventions can reduce and even reverse the
      pathologic consequences of this disease, if detected early.

PMID- 24277674
TI  - Nonalcoholic fatty liver disease and type 2 diabetes in obese children.
AB  - Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and
      adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2
      conditions are complex and it is difficult to decipher whether one drives the
      other or vice versa. Genetic predispositions, along with obesity, are probably
      shared culprits of both. NAFLD may precede the diagnosis of diabetes and play a
      critical role of driving its development by way of increasing hepatic and whole
      body insulin resistance. On the other hand, T2DM is associated with
      hyperinsulinemia, a resistance to some of the effects of gut derived peptides and
      increased systemic free fatty acids, that can all promote hepatic lipid
      deposition. Thus, each condition may promote the development of the other and
      their mutual presence creates a vicious cycle. Upon studying this complex
      interplay from another angle, reduction of liver fat significantly improves
      glucose metabolism in patients with T2DM highlighting the tight
      pathophysiological link between them.

PMID- 24277675
TI  - Depression and quality of life in youth-onset type 2 diabetes mellitus.
AB  - Type 2 Diabetes Mellitus (T2DM) was characteristically an adult-onset illness
      until recently, when it became recognized as an increasing problem among youth in
      conjunction with escalating rates and associated risks of pediatric. Youth-onset
      T2DM is associated with a range of psychosocial risk factors, and research
      underscores the relevancy of depressive symptoms and quality of life factors in
      illness diagnosis, management and prognosis. This review paper summarizes
      available findings on depression and health-related quality of life for youth
      onset T2DM, and provides recommendations for clinical practice and a conceptual
      framework for further studies.

PMID- 24277676
TI  - Vitamin D and gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) complicates 7 %-14 % of pregnancies in the
      United States. Vitamin D deficiency also is common in pregnancy. Emerging
      evidence suggests that Vitamin D administration can improve insulin sensitivity
      and glucose tolerance, but whether vitamin D supplementation can prevent GDM is
      unknown. Observational studies provide conflicting evidence as to whether low
      serum 25-hydroxyvitmain D (25(OH)D) levels are associated with GDM. Two recent
      systematic reviews concluded that vitamin D deficiency is associated with a
      higher risk of GDM. However, these reviews are limited by the observational and
      diverse nature of the included studies. Of greatest concern is the inability to
      understand how important confounding variables such as race/ethnicity and
      adiposity might affect the association. Randomized controlled trial data remain
      limited but are critical to understanding whether supplementation with vitamin D
      beyond what is contained in routine prenatal vitamins will prevent GDM or improve
      glucose tolerance for women with GDM.

PMID- 24277677
TI  - Capillary zone electrophoresis for analysis of complex proteomes using an
      electrokinetically pumped sheath flow nanospray interface.
AB  - The vast majority of proteomic studies employ RP-HPLC coupled with MS/MS for
      analysis of the tryptic digest of a cellular lysate. This technology is quite
      mature, and typically provides identification of hundreds to thousands of
      peptides, which is used to infer the identity of hundreds to thousands of
      proteins. These studies usually require milligrams to micrograms of starting
      material. CZE provides an interesting alternative separation method based on a
      different separation mechanism than HPLC. CE received some attention for protein
      analysis beginning 25 years ago. Those efforts stalled because of the limited
      performance of the electrospray interfaces and the limited speed and sensitivity
      of mass spectrometers of that era. This review considers a new electrospray
      interface design coupled with Orbitrap Velos and linear Q-trap mass
      spectrometers. CZE coupled with this interface and these detectors provides
      single shot detection of >1250 peptides from an Escherichia coli digest in less
      than 1 h, identification of nearly 5000 peptides from analysis of seven fractions
      produced by SPE of the E. coli digest in a 6 h total analysis time, low attomole
      detection limits for peptides generated from standard proteins, and high
      zeptomole detection limits for selected ion monitoring of peptides. Incorporation
      of an integrated on-line immobilized trypsin microreactor allows digestion and
      analysis of picogram amounts of a complex eukaryotic proteome. 

PMID- 24277678
TI  - Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with
      olmesartan versus other angiotensin receptor blockers.
AB  - PURPOSE: In the randomized trial, Randomized Olmesartan and Diabetes
      Microalbuminuria Prevention, acute cardiovascular death was increased nearly
      fivefold in diabetic patients treated with high-dose olmesartan, an angiotensin
      receptor blocker (ARB), compared with placebo. METHODS: Medicare beneficiaries
      were entered into new-user cohorts of olmesartan or other ARBs and followed on
      therapy for occurrence of acute myocardial infarction, stroke, or death. Analyses
      focused on specific subgroups defined by diabetes status, ARB dose, and duration
      of therapy. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated
      using Cox proportional hazards regression, with other ARBs as reference. RESULTS:
      A total of 158,054 olmesartan and 724,673 other ARB users were followed for
      54,285 and 260,390 person-years, respectively, during which 9237 endpoint events
      occurred. Lower-dose olmesartan was not associated with increased risk for any
      endpoint, regardless of duration of use. High-dose olmesartan for 6 months or
      longer was associated with increased risk of death in patients with diabetes (HR
      2.03, 95%CI 1.09-3.75, p = 0.02) and with reduced risk in nondiabetic patients
      (HR 0.46, 95%CI 0.24-0.86, p = 0.01). Some, but not all, sensitivity analyses
      suggested that selective prescribing of olmesartan to healthier patients
      (channeling bias) may have accounted for the reduced risk in nondiabetic
      patients. CONCLUSIONS: High-dose olmesartan was associated with an increased risk
      of death in diabetic patients treated for 6 months or longer and with a reduced
      risk of death in nondiabetic patients, when compared with use of other ARBs. This
      latter effect was probably because of selective prescribing of olmesartan to
      healthier patients, although effect modification cannot be excluded. Published
      2013. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 24277679
TI  - Evidence for serotonin as a relevant inducer of liver regeneration after liver
      resection in humans.
AB  - Liver regeneration (LR) involves a complex interplay of growth factors and
      antagonists. In this context, platelet-derived serotonin (5-HT) has been
      identified as a critical inducer of LR in mice. Clinical evidence for a role of 5
      HT in LR in humans is lacking. Accordingly, serum and plasma 5-HT was monitored
      perioperatively in 60 patients undergoing liver resection, of which 35 served as
      exploration and 25 as validation sets. Intraplatelet (IP) levels of 5-HT were
      calculated by subtraction of plasma 5-HT from serum values. Serum markers of
      liver function were used to evaluate LR and liver dysfunction (LD). In the
      exploration setting, IP 5-HT levels significantly decreased after liver resection
      (P < 0.001) and gradually recovered during the first week. IP 5-HT measured
      before surgery specifically predicted LD in the subsequent 7 days (area under the
      curve: 0.721; P = 0.029). Patients suffering from postoperative LD and morbidity
      were found to have reduced IP 5-HT levels during the entire perioperative period.
      Furthermore, we validated that reduced preoperative IP 5-HT (<73 ng/mL) was
      associated with an increased incidence of postoperative LD and morbidity (P =
      0.045 and P = 0.021) and were able to demonstrate that IP 5-HT levels were an
      independent predictor of poor clinical outcome. CONCLUSIONS: These findings
      provide evidence that IP 5-HT correlates with LR in humans: Patients with low IP
      5-HT before liver resection suffered from delayed hepatic regeneration.
      Therefore, IP 5-HT levels may prove a helpful clinical marker to predict
      postoperative LD and clinical outcome before hepatic resection and initiate
      suitable interventions.

PMID- 24277680
TI  - Insulin degludec: pharmacokinetic properties in subjects with hepatic impairment.
AB  - BACKGROUND AND OBJECTIVE: Insulin degludec is a basal insulin with a slow and
      distinct absorption mechanism resulting in an ultra-long, flat, and stable
      pharmacokinetic profile in patients with diabetes mellitus. The aim of this study
      was to examine the effect of hepatic impairment on the single-dose
      pharmacokinetics of insulin degludec. METHODS: Twenty-four subjects, allocated to
      one of four groups (n=6 per group) based on level of hepatic impairment (normal
      hepatic function, Child-Pugh grade A, B, or C), were administered a single
      subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post
      dose and fractionated urine samples were collected to measure pharmacokinetic
      parameters. RESULTS: No difference was observed in pharmacokinetic parameters
      [area under the 120-h serum insulin degludec concentration-time curve (AUC120 h),
      maximum insulin degludec concentration (C max), and apparent clearance (CL/F)]
      for subjects with impaired versus normal hepatic function after a single dose of
      insulin degludec. The geometric mean [coefficient of variation (CV) %] AUC120 h
      values were 89,092 (16), 83,327 (15), 88,944 (23), and 79,846 (19) pmol.h/L for
      normal hepatic function and mild, moderate, and severe hepatic impairment,
      respectively. Simulated steady-state insulin degludec pharmacokinetic profiles
      showed an even distribution of exposure across a 24-h dosing interval regardless
      of hepatic function status. CONCLUSIONS: The ultra-long pharmacokinetic
      properties of insulin degludec were preserved in subjects with hepatic impairment
      and there were no statistically significant differences in absorption or
      clearance compared with subjects with normal hepatic function.

PMID- 24277681
TI  - Prophylactic interventions after delivery of placenta for reducing bleeding
      during the postnatal period.
AB  - BACKGROUND: There are several Cochrane systematic reviews looking at postpartum
      haemorrhage (PPH) prophylaxis in the third stage of labour and another Cochrane
      review investigating the timing of prophylactic uterotonics in the third stage of
      labour (i.e. before or after delivery of the placenta). There are, however, no
      Cochrane reviews looking at the use of interventions given purely after delivery
      of the placenta. Ergometrine or methylergometrine are used for the prevention of
      PPH in the postpartum period (the period after delivery of the infant) after
      delivery of the placenta in some countries. There are, furthermore, no Cochrane
      reviews that have so far considered herbal therapies or homeopathic remedies for
      the prevention of PPH after delivery of the placenta. OBJECTIVES: To assess the
      effectiveness of available prophylactic interventions for PPH including
      prophylactic use of ergotamine, ergometrine, methylergometrine, herbal therapies,
      and homeopathic remedies, administered after delivery of the placenta, compared
      with no uterotonic agents as well as with different routes of administration for
      prevention of PPH after delivery of the placenta. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013), The
      Food and Drug Administration (FDA) (USA),  Medicines and Healthcare Products
      Regulatory Agency (MHRA) (UK), European Medicines Agency (EMA) (EU),
      Pharmaceuticals and Medical Devices Agency (PMDA) (Japan),  Therapeutic Goods
      Administration (TGA) (Australia), ClinicalTrials.gov, Current Controlled Trials,
      WHO International Clinical Trials Registry Platform (ICTRP), University Hospital
      Medical Information Network Clinical Trials Registry (UMIN-CTR; Japan), Japan
      Pharmaceutical Information Center Clinical Trials Information (Japic-CTI; Japan),
      Japan Medical Association Clinical Trial Registration (JMACCT CTR; Japan) (all on
      30 April 2013) and reference lists of retrieved studies SELECTION CRITERIA: All
      randomised or quasi-randomised controlled trials comparing prophylactic
      ergotamine, ergometrine, methylergometrine, herbal therapies, and homeopathic
      remedies (using any route and timing of administration) during the postpartum
      period after delivery of the placenta with no uterotonic agents or trials
      comparing different routes or timing of administration of ergotamine,
      ergometrine, methylergometrine, herbal therapies, and homeopathic remedies,
      during the postpartum period after delivery of the placenta. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial eligibility and the
      methodological quality of trials, extracted data using the agreed form. Data were
      checked for accuracy. MAIN RESULTS: Five randomised studies involving 1466 women
      met the inclusion criteria. All studies were classified as having an unclear risk
      of bias. Two studies (involving 1097 women) compared oral methylergometrine with
      a placebo, and one (involving 171 women) compared oral methylergometrine with
      Kyuki-chouketsu-in, a Japanese traditional herbal medicine. The remaining two
      studies (involving 198 women) did not report the outcomes of interest for this
      review. None of the included studies reported primary outcomes prespecified in
      the review protocol (blood loss of 1000 mL or more over the period of
      observation, maternal death or severe morbidity). Overall, there was no clear
      evidence of differences between groups in the following PPH outcomes: blood loss
      of 500 mL or more (risk ratio (RR) 1.45; 95% confidence interval (CI) 0.39 to
      5.47, two studies), amount of lochia during the first 72 hours of the puerperium
      (mean difference (MD) -25.00 g; 95% CI -69.79 to 19.79, one study), or amount of
      lochia by four weeks postpartum (MD -7.00 g; 95% CI -23.99 to 9.99).The Japanese
      study with a relatively small sample size comparing oral methylergometrine with a
      Japanese traditional herbal medicine found that oral methylergometrine
      significantly increased the blood haemoglobin concentration at day one postpartum
      (MD 0.50 g/dL; 95% CI 0.11 to 0.89) compared to herbal medicine. Adverse events
      were not well-reported in the included studies. We did not find any studies
      comparing homeopathic remedies with either a placebo or no treatment. AUTHORS'
      CONCLUSIONS: There was insufficient evidence to support the use of prophylactic
      oral methylergometrine given after delivery of the placenta for the prevention of
      PPH. Additionally, the effectiveness of prophylactic use of herbal medicine or
      homeopathic remedies for PPH is still unclear as we could not find any clear
      evidence. Trials to assess the effectiveness of herbal medicines and homeopathic
      remedies in preventing PPH are warranted.

PMID- 24277682
TI  - Emotional and temperamental correlates of Type A in children and adolescents.
AB  - Emotional and behavioral correlates of Type A behavior in children and
      adolescents were examined in 184 fifth-, seventh-, and ninth-grade students,
      classified as high or low Type A, using self-report, teacher ratings (fifth grade
      only), and structured interview procedures. Measures included the Hunter-Wolf A-B
      Rating Scale, Behavioral Symptoms of Stress Inventory, Dimensions of Temperament
      Survey, Desire for Control Scale, Eysenck Personality Inventory, and the Multiple
      Affect Adjective Checklist. High Type A children reported significantly more
      stressed-related behaviors, higher levels of depression, anger, anxiety, and
      cognitive disorganization, and greater reactivity than Low Type A. No differences
      were found on measures of temperament (activity level, attention span,
      adaptibility, and rhythmicity), desire for control, or introversion-extroversion.
      Females, in general, reported significantly more behavioral stress symptoms.
      However, no other gender differences were found. Possible reasons for reported
      differences between Type A children and adults are discussed, along with gender
      differences in behavioral symptoms. Need for multiple measures of Type A across
      situation is considered along with need for controlled longitudinal studies of
      Type A components and the influence of contexts. 

PMID- 24277683
TI  - An observational study of affective and assertive family interactions during
      adolescence.
AB  - The purpose of this study was to describe the role of affective and assertive
      interactions in familial adaptation to adolescent pubertal development. Twenty
      five family triads consisting of the adolescent and parents were asked to engage
      in an Unrevealed Differences task. This interaction was audiorecorded, and
      statements were coded as affective or assertive using a modified version of
      Bales's ([1970) Personality and Interpersonal Behavior, Holt, Rhinehart and
      Winston, Inc., New York) Interaction Process Analysis. Family relationships
      appear redefined during transpuberty, a time when physical changes associated
      with the onset of puberty are at apeak. This redefinition of transpubertal family
      relations is characterized by a decline in the use of affective statements
      coupled with an increase in the use of assertive statements relative to
      prepubertal and postpubertal families. Differences in mother-adolescent and
      father-adolescent interactions also are discussed. 

PMID- 24277684
TI  - Identity development in late adolescence: Causal modeling of social and familial
      influences.
AB  - The purpose of this study was to develop a causal model to examine the ways in
      which familial and social variables influence identity development in late
      adolescence. Four hundred and ten 18-to 21-year-old male and female college
      students at a large Midwestern university completed a questionnaire assessing
      familial security, familial and social relations, and three dimensions of
      identity. The resulting causal models indicated that security in familial
      relations enhanced identity development directly, and also indirectly by
      initially enhancing adolescents' social confidence and degree of interpersonal
      affiliation. However, the pattern of interaction among these variables varied
      with sex and with the specific identity measure used. It is suggested that
      security in familial relations may provide the support for meaningful exploration
      and experimentation, and enhance aspects of adolescents' sociability, which, when
      taken together, may enhance the identity formation process. 

PMID- 24277685
TI  - Transcultural comparisons of self-image in German and United States adolescents.
AB  - Based on the Offer Selfimage Questionnaire (OSIQ), the selfimage of German and
      United States adolescents was compared. The German study was based on OSIQ
      protocols from 365 adolescents in West Berlin while the American sample comprised
      adolescents drawn from seven cities in the United States. With respect to three
      scales, United States adolescents report better adjustment than do the German
      adolescents. These scales were Mastery of the External World, Vocational and
      Educational Goals, and Superior Adjustment. In general, these two Western
      societies share more similarities than differences in the selfimages of their
      adolescents. 

PMID- 24277686
TI  - Educational correlates of adolescents' sexual attitudes and behavior.
AB  - Parents' educational attainment is known to be related to their children's
      educational aspirations and plans, and these variables have been presumed to be
      inversely related to early adolescent sexual activity. Relationships between
      these educational variables and adolescents' sexual attitudes and behavior were
      analyzed in a sample of 810 high school students from two Western states.
      Parents' educational background was positively related to adolescents'
      educational plans and performance, and these educational variables were inversely
      related to adolescents' premarital sexual attitudes and intercourse experience.
      It seems most plausible to conclude that parents' educational backgrounds affect
      children's educational interests and grades, which, in turn, affect adolescent
      sexuality. However, the observed associations also could be interpreted to
      suggest that early sexual behavior reduces adolescents' educational plans and
      lowers their school grades. 

PMID- 24277687
TI  - Substance use by hispanic and white non-hispanic pregnant adolescents: A
      preliminary survey.
AB  - White non-Hispanic and Hispanic adolescents aged 17 years and under n= 81) who
      delivered in San Jose, California area hospitals during a 6-week period were
      interviewed within 24 hours concerning their use of cigarettes, marijuana, and
      alcohol during pregnancy, and a number of background, social support, and
      psychosocial factors. Before 12-16 weeks of pregnancy, each of the substances
      studied was used by over 50% of this population, with 53% smoking cigarettes, 51%
      smoking marijuana, and 58% consuming beer or wine. Most substance use ceased
      after 12-16 weeks of pregnancy. There were no significant differences between
      ethnic groups in substance use. Multiple regression analyses showed that
      cigarette smoking decreased when social support was provided by the adolescent's
      partner and it was higher if parents smoked and/or used alcohol p<.001. Parental
      substance use, combined with lack of social support, was also associated
      significantly with marijuana use p<.001, explaining 30% of the variance. Use of
      birth control prior to pregnancy was related to beer and wine consumption p<.05,
      explaining 16% of the variance. Active inclusion of members of the adolescent's
      support network in pregnancy care, and initiative by educators and clinicians in
      discussing substance use, may accelerate its cessation. Ethnicityrelated behavior
      change strategies may be of little relevance to adolescent substance use during
      pregnancy. 

PMID- 24277688
TI  - The transition to junior high school: Beliefs of pre- and posttransition
      teachers.
AB  - The beliefs of 107 teachers who students have for mathematics the last year of
      elementary school are compared to the beliefs of 64 teachers the same students
      have for mathematics the first year of junior high school. As hypothesized,
      posttransition teachers trust students less, believe more strongly in controlling
      and disciplining students, and have a weaker sense of teaching efficacy than do
      pretransition teachers. There are no significant differences in beliefs about the
      nature of ability as a fixed trait. It is suggested that societal stereotypes
      about early adolescents may flourish in school settings that are exclusively for
      that age group, so that teachers believe these students are unlikely to make much
      academic progress and must be controlled. 

PMID- 24277690
TI  - Editors' overview perspectives on teaching social responsibility to students in
      science and engineering.
AB  - Global society is facing formidable current and future problems that threaten the
      prospects for justice and peace, sustainability, and the well-being of humanity
      both now and in the future. Many of these problems are related to science and
      technology and to how they function in the world. If the social responsibility of
      scientists and engineers implies a duty to safeguard or promote a peaceful, just
      and sustainable world society, then science and engineering education should
      empower students to fulfil this responsibility. The contributions to this special
      issue present European examples of teaching social responsibility to students in
      science and engineering, and provide examples and discussion of how this teaching
      can be promoted, and of obstacles that are encountered. Speaking generally,
      education aimed at preparing future scientists and engineers for social
      responsibility is presently very limited and seemingly insufficient in view of
      the enormous ethical and social problems that are associated with current science
      and technology. Although many social, political and professional organisations
      have expressed the need for the provision of teaching for social responsibility,
      important and persistent barriers stand in the way of its sustained development.
      What is needed are both bottom-up teaching initiatives from individuals or groups
      of academic teachers, and top-down support to secure appropriate embedding in the
      university. Often the latter is lacking or inadequate. Educational policies at
      the national or international level, such as the Bologna agreements in Europe,
      can be an opportunity for introducing teaching for social responsibility.
      However, frequently no or only limited positive effect of such policies can be
      discerned. Existing accreditation and evaluation mechanisms do not guarantee
      appropriate attention to teaching for social responsibility, because, in their
      current form, they provide no guarantee that the curricula pay sufficient
      attention to teaching goals that are desirable for society as a whole. 

PMID- 24277689
TI  - The complex evolutionary dynamics of Hsp70s: a genomic and functional
      perspective.
AB  - Hsp70 molecular chaperones are ubiquitous. By preventing aggregation, promoting
      folding, and regulating degradation, Hsp70s are major factors in the ability of
      cells to maintain proteostasis. Despite a wealth of functional information,
      little is understood about the evolutionary dynamics of Hsp70s. We undertook an
      analysis of Hsp70s in the fungal clade Ascomycota. Using the well-characterized
      14 Hsp70s of Saccharomyces cerevisiae, we identified 491 orthologs from 53
      genomes. Saccharomyces cerevisiae Hsp70s fall into seven subfamilies: four
      canonical-type Hsp70 chaperones (SSA, SSB, KAR, and SSC) and three atypical
      Hsp70s (SSE, SSZ, and LHS) that play regulatory roles, modulating the activity of
      canonical Hsp70 partners. Each of the 53 surveyed genomes harbored at least one
      member of each subfamily, and thus establishing these seven Hsp70s as units of
      function and evolution. Genomes of some species contained only one member of each
      subfamily that is only seven Hsp70s. Overall, members of each subfamily formed a
      monophyletic group, suggesting that each diversified from their corresponding
      ancestral gene present in the common ancestor of all surveyed species. However,
      the pattern of evolution varied across subfamilies. At one extreme, members of
      the SSB subfamily evolved under concerted evolution. At the other extreme, SSA
      and SSC subfamilies exhibited a high degree of copy number dynamics, consistent
      with a birth-death mode of evolution. KAR, SSE, SSZ, and LHS subfamilies evolved
      in a simple divergent mode with little copy number dynamics. Together, our data
      revealed that the evolutionary history of this highly conserved and ubiquitous
      protein family was surprising complex and dynamic.

PMID- 24277692
TI  - Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen
      receptor/Liver X receptor pathway in mice.
AB  - Liver X receptor (LXR) activation stimulates triglyceride (TG) accumulation in
      the liver. Several lines of evidence indicate that estradiol-17beta (E2) reduces
      TG levels in the liver; however, the molecular mechanism underlying the E2 effect
      remains unclear. Here, we show that administration of E2 attenuated sterol
      regulatory element-binding protein (SREBP)-1 expression and TG accumulation
      induced by LXR activation in mouse liver. In estrogen receptor alpha (ERalpha)
      knockout (KO) and liver-specific ERalpha KO mice, E2 did not affect SREBP-1
      expression or TG levels. Molecular analysis revealed that ERalpha is recruited to
      the SREBP-1c promoter through direct binding to LXR and inhibits coactivator
      recruitment to LXR in an E2-dependent manner. Our findings demonstrate the
      existence of a novel liver-dependent mechanism controlling TG accumulation
      through the nonclassical ER/LXR pathway. To confirm that a nonclassical ER/LXR
      pathway regulates ERalpha-dependent inhibition of LXR activation, we screened
      ERalpha ligands that were able to repress LXR activation without enhancing
      ERalpha transcriptional activity, and, as a result, we identified the
      phytoestrogen, phloretin. In mice, phloretin showed no estrogenic activity;
      however, it did reduce SREBP-1 expression and TG levels in liver of mice fed a
      high-fat diet to an extent similar to that of E2. CONCLUSION: We propose that ER
      ligands reduce TG levels in the liver by inhibiting LXR activation through a
      nonclassical pathway. Our results also indicate that the effects of ER on TG
      accumulation can be distinguished from its estrogenic effects by a specific ER
      ligand.

PMID- 24277691
TI  - Influence of breastfeeding on blood-cell transcript-based biomarkers of health in
      children.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The expression of specific genes in
      peripheral blood cells (PBCs) may be used as biomarkers of the metabolic status.
      High levels of expression of CPT1A, SLC27A2, INSR, LEPR, FASN and PPARalpha in
      PBCs are indicative of a lower risk for the insulin resistant or dyslipidaemic
      state associated with obesity in children. Breastfeeding seems to confer
      protective effects against obesity and its related metabolic problems. WHAT THIS
      STUDY ADDS: Children who had been breastfed showed higher expression levels of
      SLC27A2, FASN, PPARalpha and INSR in PBCs compared with formula-fed subjects. The
      relationship of the PBC transcript levels of SLC27A2, INSR, FASN and PPARalpha
      with insulin resistance and dyslipidaemia may be dependent on the type of infant
      feeding (breast vs. formula). The transcript levels of the mentioned biomarkers
      could be useful to distinguish the formula-fed children who are at higher risk of
      metabolic alterations. BACKGROUND: Blood-cell transcripts have showed to be good
      biomarkers of metabolic alterations and their use in early detection and
      prevention of future disorders is promising. OBJECTIVE: This study aimed to
      examine the relation between previously proposed transcriptional biomarkers of
      metabolic health (SLC27A2, CPT1A, FASN, PPARalpha, INSR, LEPR) in peripheral
      blood cells and the type of infant feeding in a subset of children from the
      IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health
      Effects in Children and Infants) cohort. SUBJECTS: A total of 237 children aged 2
      9 years from eight European countries were studied. RESULTS: Breastfed children
      showed higher expression levels of SLC27A2, FASN, PPARalpha and INSR, and lower
      risk of being overweight and of having high plasma triglyceride levels vs.
      formula-fed children. Besides, overweight formula-fed children presented higher
      HOMA-index than overweight breastfed children (1.90 vs. 1.62); however, this
      negative effect was absent in formula-fed children with high expression of
      SLC27A2. Moreover, formula-fed children with low expression of SLC27A2, FASN,
      PPARalpha and INSR presented higher triglyceride levels than subjects with high
      expression of these genes (77.7 mg dL(-1) vs. 44.8 mg dL(-1) ). This difference
      was absent in breastfed children. CONCLUSIONS: Protective effects of
      breastfeeding are reflected in higher expression levels of SLC27A2, FASN,
      PPARalpha and INSR in blood cells. These biomarkers may also serve to
      discriminate the formula-fed children that are at higher risk of metabolic
      alterations.

PMID- 24277693
TI  - Layer-by-layer assembly of multilayer films for controlled drug release.
AB  - Drug efficacy has been improved using various methods that enhance targeting,
      decrease toxicity, and facilitate timely and sustained drug release. To achieve
      these properties, various drug loading and release platforms have been developed.
      Layer-by-layer (LbL) self-assembly is widely used to generate controlled and
      sustained drug release LbL multilayer films because it allows desired functions
      and structures to be obtained through a simple procedure. In this review article,
      we highlight controlled drug release from LbL self-assembling films with diverse
      release kinetics, particularly with regard to mechanisms of drug release. 

PMID- 24277694
TI  - Simultaneous determination of bioactive marker compounds from Gardeniae fructus
      by high performance liquid chromatography.
AB  - Gardeniae fructus is one of the medicinal herbs that have been used in Far
      Eastern countries, such as Korea, China, and Japan. Gardeniae fructus is the
      dried ripe fruit of Gardenia jasminoides Ellis (Rubiaceae) and has been used as a
      yellow dye. It is widely used as traditional herbal medicine for reducing fever,
      cholagogue, diuretic and antiphlogistic effects. We established an analytical
      method that was useful to evaluate the quality control, and standardize
      quantification monitoring of 68 samples of Gardeniae fructus collected from Korea
      and China. While numerous previous studies have focused on the simultaneous
      analysis of geniposide, which constitutes the higher proportion of Gardeniae
      fructus, and crocin, which determines its color, no simultaneous analysis of
      gardenoside and geniposide, the major components of Gardeniae Fructus, has been
      performed. However, previously reported methods are not considered accurate
      enough because only geniposide or gardenoside was chosen to be the marker
      component for the quality control of Gardeniae fructus. Thus, we developed the
      method using simultaneous determination of four components including geniposide,
      gardenoside, geniposic acid and chlorogenic acid. Against this backdrop, this
      study aims to propose a new calculation for gardenoside and geniposide
      concentrations by analyzing their concentrations in Gardeniae fructus. 

PMID- 24277695
TI  - T lymphocyte-dependent and -independent regulation of Cxcl8 expression in
      zebrafish intestines.
AB  - CXCL8 is a potent neutrophil recruiting chemokine. CXCL8 is produced by several
      innate immune cells, including neutrophils, macrophages, as well as epithelial
      cells. Although previously considered only to be produced as a result of TLR
      signaling in these cells, recent reports show that T cell-derived cytokines also
      induce CXCL8 in epithelial cells. Likewise, we observed that T cell inhibition
      diminished intestinal production of functional mouse homologs of CXCL8 in the
      early phase of enterocolitis. In this study, we specifically investigated whether
      adaptive cells contribute to innate cxcl8 expression in the intestines. To this
      end, we used the zebrafish as our model system. Unlike murine models that lack
      CXCL8, zebrafish have two CXCL8 chemokines that are both elevated after an acute
      inflammatory stimulus and recruit neutrophils. Furthermore, zebrafish develop
      innate and adaptive immunity sequentially, enabling analysis of intestinal cxcl8
      expression in the absence (<3 wk of age) and presence (>3 wk of age) of adaptive
      immunity. In this study, we show that intestinal cxcl8-l1 but not cxcl8-l2
      expression is regulated by T lymphocytes under homeostatic conditions. In
      contrast, during intestinal inflammation especially, cxcl8-l1 expression is
      upregulated independent of T lymphocyte presence. Furthermore, we show that human
      CXCL8 is able to induce intestinal zebrafish neutrophil recruitment and cxcl8-l1
      expression, demonstrating that zebrafish can be used as a model to study CXCL8
      function and regulation. In conclusion, these data provide evidence that Cxcl8-l1
      and Cxcl8-l2 are differentially regulated via T lymphocyte-dependent and 
      independent mechanisms during homeostasis and inflammation. 

PMID- 24277696
TI  - Thrombin-induced CCAAT/enhancer-binding protein beta activation and IL-8/CXCL8
      expression via MEKK1, ERK, and p90 ribosomal S6 kinase 1 in lung epithelial
      cells.
AB  - Thrombin, a serine protease, is a well-known coagulation factor generated during
      vascular injury and plays an important role in lung inflammation. We previously
      showed that the c-Src- and Rac/PI3K/Akt-dependent NF-kappaB pathways are involved
      in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells (A549).
      In this study, we investigated the role of the MEK kinase (MEKK)1/ERK/p90
      ribosomal S6 kinase (RSK)1-dependent C/EBPbeta signaling pathway in thrombin
      induced IL-8/CXCL8 expression. Thrombin-induced IL-8/CXCL8 release and IL-8/CXCL8
      luciferase activity were attenuated by small interfering RNA (siRNA) of C/EBPbeta
      and by cells transfected with the C/EBPbeta site mutation of the IL-8/CXCL8
      construct. Moreover, thrombin-induced kappaB-luciferase activity was also
      inhibited by C/EBPbeta siRNA. The thrombin-induced increases in IL-8/CXCL8
      release and IL-8/CXCL8-luciferase were also inhibited by MEKK1 siRNA, PD98059 (an
      MEK inhibitor), U0126 (an ERK inhibitor), and RSK1 siRNA. Treatment of cells with
      thrombin caused an increase in C/EBPbeta phosphorylation at Thr(235), C/EBPbeta
      luciferase activity, recruitment of C/EBPbeta to the IL-8/CXCL8 promoter, and
      C/EBPbeta-specific DNA complex formation. Furthermore, thrombin-mediated
      C/EBPbeta phosphorylation and C/EBPbeta-luciferase activity were inhibited by
      MEKK1 siRNA, PD98059, and RSK1 siRNA. Stimulation of cells with thrombin resulted
      in an increase in RSK1 phosphorylation at Thr(359)/Ser(363), and this effect was
      inhibited by MEKK1 siRNA and PD98059. The thrombin-induced increase in ERK
      activation was inhibited by MEKK1 siRNA. These results imply that thrombin
      activates the MEKK1/ERK/RSK1 signaling pathway, which in turn initiates C/EBPbeta
      activation, recruitment of C/EBPbeta to the IL-8/CXCL8 promoter, and C/EBPbeta
      specific DNA complex formation, and ultimately induces IL-8/CXCL8 expression and
      release in lung epithelial cells. 

PMID- 24277697
TI  - Akt2 deficiency protects from acute lung injury via alternative macrophage
      activation and miR-146a induction in mice.
AB  - Acute respiratory distress syndrome (ARDS) is a major cause of respiratory
      failure, with limited effective treatments available. Alveolar macrophages
      participate in the pathogenesis of ARDS. To investigate the role of macrophage
      activation in aseptic lung injury and identify molecular mediators with
      therapeutic potential, lung injury was induced in wild-type (WT) and Akt2(-/-)
      mice by hydrochloric acid aspiration. Acid-induced lung injury in WT mice was
      characterized by decreased lung compliance and increased protein and cytokine
      concentration in bronchoalveolar lavage fluid. Alveolar macrophages acquired a
      classical activation (M1) phenotype. Acid-induced lung injury was less severe in
      Akt2(-/-) mice compared with WT mice. Alveolar macrophages from acid-injured
      Akt2(-/-) mice demonstrated the alternative activation phenotype (M2). Although
      M2 polarization suppressed aseptic lung injury, it resulted in increased lung
      bacterial load when Akt2(-/-) mice were infected with Pseudomonas aeruginosa. miR
      146a, an anti-inflammatory microRNA targeting TLR4 signaling, was induced during
      the late phase of lung injury in WT mice, whereas it was increased early in Akt2(
      /-) mice. Indeed, miR-146a overexpression in WT macrophages suppressed LPS
      induced inducible NO synthase (iNOS) and promoted M2 polarization, whereas miR
      146a inhibition in Akt2(-/-) macrophages restored iNOS expression. Furthermore,
      miR-146a delivery or Akt2 silencing in WT mice exposed to acid resulted in
      suppression of iNOS in alveolar macrophages. In conclusion, Akt2 suppression and
      miR-146a induction promote the M2 macrophage phenotype, resulting in amelioration
      of acid-induced lung injury. In vivo modulation of macrophage phenotype through
      Akt2 or miR-146a could provide a potential therapeutic approach for aseptic ARDS;
      however, it may be deleterious in septic ARDS because of impaired bacterial
      clearance. 

PMID- 24277698
TI  - Cancer-initiating cells from colorectal cancer patients escape from T cell
      mediated immunosurveillance in vitro through membrane-bound IL-4.
AB  - Cancer-initiating cells (CICs) that are responsible for tumor initiation,
      propagation, and resistance to standard therapies have been isolated from human
      solid tumors, including colorectal cancer (CRC). The aim of this study was to
      obtain an immunological profile of CRC-derived CICs and to identify CIC
      associated target molecules for T cell immunotherapy. We have isolated cells with
      CIC properties along with their putative non-CIC autologous counterparts from
      human primary CRC tissues. These CICs have been shown to display "tumor
      initiating/stemness" properties, including the expression of CIC-associated
      markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenicity
      following injection in immunodeficient mice. The immune profile of these cells
      was assessed by phenotype analysis and by in vitro stimulation of PBMCs with CICs
      as a source of Ags. CICs, compared with non-CIC counterparts, showed weak
      immunogenicity. This feature correlated with the expression of high levels of
      immunomodulatory molecules, such as IL-4, and with CIC-mediated inhibitory
      activity for anti-tumor T cell responses. CIC-associated IL-4 was found to be
      responsible for this negative function, which requires cell-to-cell contact with
      T lymphocytes and which is impaired by blocking IL-4 signaling. In addition, the
      CRC-associated Ag COA-1 was found to be expressed by CICs and to represent, in an
      autologous setting, a target molecule for anti-tumor T cells. Our study provides
      relevant information that may contribute to designing new immunotherapy protocols
      to target CICs in CRC patients. 

PMID- 24277699
TI  - Eliminating encephalitogenic T cells without undermining protective immunity.
AB  - The current clinical approach for treating autoimmune diseases is to broadly
      blunt immune responses as a means of preventing autoimmune pathology. Among the
      major side effects of this strategy are depressed beneficial immunity and
      increased rates of infections and tumors. Using the experimental autoimmune
      encephalomyelitis model for human multiple sclerosis, we report a novel
      alternative approach for purging autoreactive T cells that spares beneficial
      immunity. The moderate and temporally limited use of etoposide, a topoisomerase
      inhibitor, to eliminate encephalitogenic T cells significantly reduces the onset
      and severity of experimental autoimmune encephalomyelitis, dampens cytokine
      production and overall pathology, while dramatically limiting the off-target
      effects on naive and memory adaptive immunity. Etoposide-treated mice show no or
      significantly ameliorated pathology with reduced antigenic spread, yet have
      normal T cell and T-dependent B cell responses to de novo antigenic challenges as
      well as unimpaired memory T cell responses to viral rechallenge. Thus, etoposide
      therapy can selectively ablate effector T cells and limit pathology in an animal
      model of autoimmunity while sparing protective immune responses. This strategy
      could lead to novel approaches for the treatment of autoimmune diseases with both
      enhanced efficacy and decreased treatment-associated morbidities. 

PMID- 24277701
TI  - Stigmatizing attitudes and beliefs about bulimia nervosa: gender, age, education
      and income variability in a community sample.
AB  - OBJECTIVE: Stigmatizing attitudes towards eating disorders negatively impacts
      treatment seeking. To determine the effect of interventions to reduce stigma, a
      measure of stigma that is simple to implement is required. This study aimed to
      develop a measure of stigmatizing attitudes and beliefs towards bulimia nervosa
      (SAB-BN) and evaluate the distribution of beliefs across gender, age, education,
      and income groups. METHOD: Participants were 1828 community adults (890 men; 938
      women) aged 18-65 sampled from the Australian Electoral Roll responded to a
      mailed questionnaire. Participants provided demographic information and completed
      the SAB-BN questionnaire. RESULTS: Five components of stigmatizing attitudes and
      beliefs were identified; advantages of BN, minimization/low seriousness,
      unreliability, social distance, and personal responsibility. Stigma was low
      except on social distance and personal responsibility sub-scales, which indicated
      negative attitudes toward people with bulimia. Men compared with women and lower
      compared with higher education and income groups held significantly higher
      stigmatizing attitudes and beliefs. There were few differences between age groups
      in stigma. Differences between demographic groups provides evidence for known
      groups validity. DISCUSSION: The SAB-BN questionnaire provides a potentially
      useful tool for evaluating stigma in relation to BN. Results provide insight into
      components of stigma and the demographic groups to whom interventions should be
      targeted.

PMID- 24277700
TI  - Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from
      benchside to clinical use.
AB  - Although antiangiogenic treatments have produced milestone advances in the
      treatment of several diseases, and have significantly extended the median
      survival of cancer patients, these agents share some weaknesses, including a
      limited impact on the overall cure rate, a fleeting effect because of redundant
      pathways or early appearance of resistance mechanisms, and the lack of predictive
      factors for treatment selection. Recent data suggest that antibodies targeting
      the vascular endothelial growth factor axis exert their activity through the
      inhibition of vascular endothelial growth factor receptor-2 phosphorylation,
      which has a pivotal role in the neoangiogenic process. Ramucirumab, a fully
      humanized monoclonal antibody specifically directed against the extracellular
      domain of the receptor, administered intravenously every 2 or 3 weeks, is
      emerging as a novel antiangiogenic opportunity. Starting with preclinical data
      and early clinical results, this concise review focuses on the development of the
      novel compound across multiple cancers (including gastrointestinal malignancies,
      breast cancer, lung carcinoma, and genitourinary tumors), and presents available
      data from randomized phase II and phase III trials. REGARD was the first phase
      III study to report on the efficacy of single-agent ramucirumab in patients with
      advanced cancer. Many other ongoing phase III trials are testing the efficacy of
      this interesting antiangiogenic compound as a single agent or in combination with
      chemotherapy in different cancer types. 

PMID- 24277702
TI  - Panresistant cytomegalovirus in a kidney transplant recipient.
AB  - Cytomegalovirus (CMV) is an important pathogen often encountered after solid
      organ transplantation and is associated with increased morbidity and mortality.
      Resistance of CMV to antiviral agents is becoming more common but with few
      treatment strategies. Two specific mutations in the CMV genome--the UL97 and UL54
      genes--correlate with antiviral drug resistance. We describe a 49-year-old, CMV
      seronegative woman who received a CMV-seropositive donor kidney transplant and
      appropriate CMV prophylaxis. Approximately 1 month after transplantation, the
      patient developed CMV viremia that responded to valganciclovir. She was later
      diagnosed with recurrent CMV infection, CMV resistance, and both the UL97 and
      UL54 gene mutations. The patient responded to foscarnet and significant reduction
      of immunosuppression; she was negative for CMV viremia for the next 12 months.
      This case illustrates the importance of having heightened awareness for the
      possibility of panresistant CMV early and decreasing immunosuppression as the
      cornerstone of treatment.

PMID- 24277704
TI  - Canada ranks low on patient safety in international comparison.

PMID- 24277705
TI  - Medical tourism driving health care disparity in Thailand.

PMID- 24277703
TI  - Association between frailty and short- and long-term outcomes among critically
      ill patients: a multicentre prospective cohort study.
AB  - BACKGROUND: Frailty is a multidimensional syndrome characterized by loss of
      physiologic and cognitive reserves that confers vulnerability to adverse
      outcomes. We determined the prevalence, correlates and outcomes associated with
      frailty among adults admitted to intensive care. METHODS: We prospectively
      enrolled 421 critically ill adults aged 50 or more at 6 hospitals across the
      province of Alberta. The primary exposure was frailty, defined by a score greater
      than 4 on the Clinical Frailty Scale. The primary outcome measure was in-hospital
      mortality. Secondary outcome measures included adverse events, 1-year mortality
      and quality of life. RESULTS: The prevalence of frailty was 32.8% (95% confidence
      interval [CI] 28.3%-37.5%). Frail patients were older, were more likely to be
      female, and had more comorbidities and greater functional dependence than those
      who were not frail. In-hospital mortality was higher among frail patients than
      among non-frail patients (32% v. 16%; adjusted odds ratio [OR] 1.81, 95% CI 1.09
      3.01) and remained higher at 1 year (48% v. 25%; adjusted hazard ratio 1.82, 95%
      CI 1.28-2.60). Major adverse events were more common among frail patients (39% v.
      29%; OR 1.54, 95% CI 1.01-2.37). Compared with nonfrail survivors, frail
      survivors were more likely to become functionally dependent (71% v. 52%; OR 2.25,
      95% CI 1.03-4.89), had significantly lower quality of life and were more often
      readmitted to hospital (56% v. 39%; OR 1.98, 95% CI 1.22-3.23) in the 12 months
      following enrolment. INTERPRETATION: Frailty was common among critically ill
      adults aged 50 and older and identified a population at increased risk of adverse
      events, morbidity and mortality. Diagnosis of frailty could improve
      prognostication and identify a vulnerable population that might benefit from
      follow-up and intervention.

PMID- 24277706
TI  - Salon. The physician's first touch.

PMID- 24277707
TI  - Will Health Canada follow US move to eliminate trans fats?

PMID- 24277708
TI  - Medical abortion in Canada: behind the times.

PMID- 24277709
TI  - Acute epiglottitis following traditional Chinese gua sha therapy.

PMID- 24277710
TI  - Take-home naloxone kits preventing overdose deaths.

PMID- 24277712
TI  - Toronto clinic addresses unique needs of transgender youth.

PMID- 24277713
TI  - Laparoscopic removal of an occult foreign body causing penetrating abdominal
      trauma in a child.

PMID- 24277714
TI  - A creative writer's journey into medical imagery.

PMID- 24277715
TI  - The clinical implications of high levels of autism spectrum disorder features in
      anorexia nervosa: a pilot study.
AB  - OBJECTIVE: This study examined autism spectrum disorder (ASD) features in
      relation to treatment completion and eating disorder psychopathology in anorexia
      nervosa (AN). METHOD: Thirty-two adult women were recruited from specialist
      eating disorder services. Features of ASD and disordered eating were measured.
      Premature termination of treatment was recorded to explore whether ASD traits had
      impact on early discharge. A healthy control group was also recruited to
      investigate ASD traits between clinical and nonclinical samples. RESULTS:
      Significant differences were found between the AN group and the healthy control
      group in obsessive-compulsive disorder traits, depression and anxiety and ASD
      traits, with significant differences between groups in Social Skill and Attention
      Switching. The AN group reported no significant relationship between disordered
      eating severity and ASD traits. No significant effect was found between ASD
      features and treatment completion. DISCUSSION: Raw data on premature termination
      of treatment, despite no statistic impact, showed that seven out of the eight
      participants with high features of ASD completed treatment as planned compared
      with 50% of those with low ASD traits. Unexpectedly, this suggests enhanced
      treatment adherence in ASD.

PMID- 24277716
TI  - A mobile insulator system to detect and disrupt cis-regulatory landscapes in
      vertebrates.
AB  - In multicellular organisms, cis-regulation controls gene expression in space and
      time. Despite the essential implication of cis-regulation in the development and
      evolution of organisms and in human diseases, our knowledge about regulatory
      sequences largely derives from analyzing their activity individually and outside
      their genomic context. Indeed, the contribution of these sequences to the
      expression of their target genes in their genomic context is still largely
      unknown. Here we present a novel genetic screen designed to visualize and
      interrupt gene regulatory landscapes in vertebrates. In this screen, based on the
      random insertion of an engineered Tol2 transposon carrying a strong insulator
      separating two fluorescent reporter genes, we isolated hundreds of zebrafish
      lines containing insertions that disrupt the cis-regulation of tissue-specific
      expressed genes. We therefore provide a new easy-to-handle tool that will help to
      disrupt and chart the regulatory activity spread through the vast noncoding
      regions of the vertebrate genome. 

PMID- 24277718
TI  - Brain activations in the premonitory phase of nitroglycerin-triggered migraine
      attacks.
AB  - Our aim was identify brain areas involved in the premonitory phase of migraine
      using functional neuroimaging. To this end, we performed positron emission
      tomography scans with H2(15)O to measure cerebral blood flow as a marker of
      neuronal activity. We conducted positron emission tomography scans at baseline,
      in the premonitory phase without pain and during migraine headache in eight
      patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory
      symptoms and migraine headache in patients with episodic migraine without aura
      who habitually experienced premonitory symptoms during spontaneous attacks. The
      main outcome was comparing the first premonitory scans in all patients to
      baseline scans in all patients. We found activations in the posterolateral
      hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and
      various cortical areas including occipital, temporal and prefrontal cortex. Brain
      activations, in particular of the hypothalamus, seen in the premonitory phase of
      glyceryl trinitrate-triggered migraine attacks can explain many of the
      premonitory symptoms and may provide some insight into why migraine is commonly
      activated by a change in homeostasis. 

PMID- 24277717
TI  - Disease progression in patients with single, large-scale mitochondrial DNA
      deletions.
AB  - Single, large-scale deletions of mitochondrial DNA are a common cause of
      mitochondrial disease and cause a broad phenotypic spectrum ranging from mild
      myopathy to devastating multi-system syndromes such as Kearns-Sayre syndrome.
      Studies to date have been inconsistent on the value of putative predictors of
      clinical phenotype and disease progression such as mutation load and the size or
      location of the deletion. Using a cohort of 87 patients with single, large-scale
      mitochondrial DNA deletions we demonstrate that a variety of outcome measures
      such as COX-deficient fibre density, age-at-onset of symptoms and progression of
      disease burden, as measured by the Newcastle Mitochondrial Disease Adult Scale,
      are significantly (P < 0.05) correlated with the size of the deletion, the
      deletion heteroplasmy level in skeletal muscle, and the location of the deletion
      within the genome. We validate these findings with re-analysis of 256 cases from
      published data and clarify the previously conflicting information of the value of
      these predictors, identifying that multiple regression analysis is necessary to
      understand the effect of these interrelated predictors. Furthermore, we have used
      mixed modelling techniques to model the progression of disease according to these
      predictors, allowing a better understanding of the progression over time of this
      strikingly variable disease. In this way we have developed a new paradigm in
      clinical mitochondrial disease assessment and management that sidesteps the
      perennial difficulty of ascribing a discrete clinical phenotype to a broad multi
      dimensional and progressive spectrum of disease, establishing a framework to
      allow better understanding of disease progression. 

PMID- 24277719
TI  - Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might
      contribute to autism spectrum disorders.
AB  - Proteins of the ProSAP/Shank family act as major organizing scaffolding elements
      within the postsynaptic density of excitatory synapses. Deletions, mutations or
      the downregulation of these molecules has been linked to autism spectrum
      disorders, the related Phelan McDermid Syndrome or Alzheimer's disease.
      ProSAP/Shank proteins are targeted to synapses depending on binding to zinc,
      which is a prerequisite for the assembly of the ProSAP/Shank scaffold. To gain
      insight into whether the previously reported assembly of ProSAP/Shank through
      zinc ions provides a crossing point between genetic forms of autism spectrum
      disorder and zinc deficiency as an environmental risk factor for autism spectrum
      disorder, we examined the interplay between zinc and ProSAP/Shank in vitro and in
      vivo using neurobiological approaches. Our data show that low postsynaptic zinc
      availability affects the activity dependent increase in ProSAP1/Shank2 and
      ProSAP2/Shank3 levels at the synapse in vitro and that a loss of synaptic
      ProSAP1/Shank2 and ProSAP2/Shank3 occurs in a mouse model for acute and prenatal
      zinc deficiency. Zinc-deficient animals displayed abnormalities in behaviour such
      as over-responsivity and hyperactivity-like behaviour (acute zinc deficiency) and
      autism spectrum disorder-related behaviour such as impairments in vocalization
      and social behaviour (prenatal zinc deficiency). Most importantly, a low zinc
      status seems to be associated with an increased incidence rate of seizures,
      hypotonia, and attention and hyperactivity issues in patients with Phelan
      McDermid syndrome, which is caused by haploinsufficiency of ProSAP2/Shank3. We
      suggest that the molecular underpinning of prenatal zinc deficiency as a risk
      factor for autism spectrum disorder may unfold through the deregulation of zinc
      binding ProSAP/Shank family members. 

PMID- 24277720
TI  - Brain volumes predict neurodevelopment in adolescents after surgery for
      congenital heart disease.
AB  - Patients with complex congenital heart disease are at risk for neurodevelopmental
      impairments. Evidence suggests that brain maturation can be delayed and pre- and
      postoperative brain injury may occur, and there is limited information on the
      long-term effect of congenital heart disease on brain development and function in
      adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of
      childhood cardiopulmonary bypass surgery with no structural brain lesions evident
      through conventional cerebral magnetic resonance imaging and 32 healthy control
      subjects underwent extensive neurodevelopmental assessment and cerebral magnetic
      resonance imaging. Cerebral scans were analysed quantitatively using surface
      based and voxel-based morphometry. Compared with control subjects, patients had
      lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter
      (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different.
      Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11%
      (corpus callosum). Adolescents with cyanotic heart disease showed more brain
      volume loss than those with acyanotic heart disease, particularly in the white
      matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain
      volume reduction correlated significantly with cognitive, motor and executive
      functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest
      that there are long-lasting cerebral changes in adolescent survivors of
      cardiopulmonary bypass surgery for congenital heart disease and that these
      changes are associated with functional outcome. 

PMID- 24277721
TI  - Physiological and anatomical decomposition of subthalamic neurostimulation
      effects in essential tremor.
AB  - Postural tremor is the leading symptom in essential tremor, but in some cases
      intention tremor and limb ataxia emerge and can become highly disabling features.
      Deep brain stimulation of the thalamus or subthalamic white matter improve tremor
      and ataxia; however, the underlying network mechanisms are enigmatic. To
      elucidate the mechanisms of deep brain stimulation in essential tremor, we
      pursued a multimodal approach combining kinematic measures of reach-to-grasp
      movements, clinical assessments, physiological measures of neuronal excitability
      and probabilistic tractography from diffusion tensor imaging. Seven patients with
      essential tremor (age 62.9 +/- 10.3 years, two females) received thalamic deep
      brain stimulation and a clinical examination of severity of limb tremor and
      ataxia at off stimulation, using therapeutic and supratherapeutic stimulation
      parameters. A reach-to-grasp task based on acoustic cues was also performed. To
      examine the electrical properties of target structures, we determined the
      chronaxie of neural elements modulated. A control group of 13 healthy subjects
      (age 56 +/- 7.6 years, five females) underwent whole-brain diffusion tensor
      imaging at 3 T. Probabilistic tractography was applied in healthy subjects from
      seeds in cerebellum and midbrain to reconstruct the connectivity pattern of the
      subthalamic area. The positions of stimulation electrodes in patients were
      transferred into probability maps and connectivity values were correlated to
      clinical outcome measures. Therapeutic stimulation improved ataxia and tremor
      mainly during the target period of the reaching paradigm (63% reduction compared
      with off stimulation). Notably the acceleration (29%) and deceleration periods
      (41%) were improved. By contrast, supratherapeutic stimulation worsened ataxia
      during the deceleration period with a 55% increase of spatial variability, while
      maintaining near complete suppression of tremor. Chronaxie measures were in the
      range of rapidly-conducting myelinated fibres with significantly different values
      for the anti-tremor effect of therapeutic stimulation (27 s) and the pro-ataxic
      effect of supratherapeutic stimulation (52 s). The degree of connectivity to the
      dentato-thalamic tract at the stimulating electrode correlated significantly with
      the reduction of tremor in the therapeutic condition. Our data suggest that
      stimulation induced tremor reduction and induction of ataxia by supratherapeutic
      stimulation are mediated by different fibre systems. Probalistic tractography
      identified the dentato-thalamic tract as a likely target of tremor suppression.
      Stimulation-induced ataxia may be caused by additional recruitment of adjacent
      fibre systems at higher amplitudes. Stimulation with short pulse duration may
      help to increase the therapeutic window and focus on the anti-tremor effect. 

PMID- 24277722
TI  - Fractalkine activates NRF2/NFE2L2 and heme oxygenase 1 to restrain tauopathy
      induced microgliosis.
AB  - The chemokine fractalkine modulates microglial responses in neurodegenerative
      diseases, including tauopathies, but the mechanistic processes and their
      relevance in human brain pathologies is not yet known. Here, we show that
      hippocampal HT22 cells expressing human TAU(P301L) mutant protein produce
      fractalkine, which in microglia activates AKT, inhibits glycogen synthase kinase
      3beta and upregulates the transcription factor NRF2/NFE2L2 and its target genes
      including heme oxygenase 1. In a mouse model of tauopathy based on stereotaxic
      delivery in hippocampus of an adeno-associated viral vector for expression of
      TAU(P301L), we confirmed that tau-injured neurons express fractalkine. NRF2- and
      fractalkine receptor-knockout mice did not express heme oxygenase 1 in microglia
      and exhibited increased microgliosis and astrogliosis in response to neuronal
      TAU(P301L) expression, demonstrating a crucial role of the fractalkine/NRF2/heme
      oxygenase 1 pathway in attenuation of the pro-inflammatory phenotype. The
      hippocampus of patients with Alzheimer's disease also exhibits increased
      expression of fractalkine in TAU-injured neurons that recruit microglia. These
      events correlated with increased levels of NRF2 and heme oxygenase 1 proteins,
      suggesting an attempt of the diseased brain to limit microgliosis. Our combined
      results indicate that fractalkine mobilizes NRF2 to limit over-activation of
      microglia and identify this new target to control unremitting neuroinflammation
      in tauopathies. 

PMID- 24277723
TI  - Seizure prophylaxis in neurocritical care: a review of evidence-based support.
AB  - Seizures are a well-described complication of acute brain injury and
      neurosurgery. Antiepileptic drugs (AEDs) are frequently utilized for seizure
      prophylaxis in neurocritical care patients. In this review, the Neurocritical
      Care Society Pharmacy Section describes the evidence associated with the use of
      AEDs for seizure prophylaxis in patients with intracerebral tumors, traumatic
      brain injury, aneurysmal subarachnoid hemorrhage, craniotomy, ischemic stroke,
      and intracerebral hemorrhage. Clear evidence indicates that the short-term use of
      AEDs for seizure prophylaxis in patients with traumatic brain injury and
      aneurysmal subarachnoid hemorrhage may be beneficial; however, evidence to
      support the use of AEDs in other disease states is less clear.

PMID- 24277724
TI  - Prevalence of eating disorders amongst dancers: a systemic review and meta
      analysis.
AB  - Eating disorders in dancers are thought to be common, but the exact rates remain
      to be clarified. The aim of this study is to systematically compile and analyse
      the rates of eating disorders in dancers. A literature search, appraisal and meta
      analysis were conducted. Thirty-three relevant studies were published between
      1966 and 2013 with sufficient data for extraction. Primary data were extracted as
      raw numbers or confidence intervals. Risk ratios and 95% confidence intervals
      were calculated for controlled studies. The overall prevalence of eating
      disorders was 12.0% (16.4% for ballet dancers), 2.0% (4% for ballet dancers) for
      anorexia, 4.4% (2% for ballet dancers) for bulimia and 9.5% (14.9% for ballet
      dancers) for eating disorders not otherwise specified (EDNOS). The dancer group
      had higher mean scores on the EAT-26 and the Eating Disorder Inventory subscales.
      Dancers, in general, had a higher risk of suffering from eating disorders in
      general, anorexia nervosa and EDNOS, but no higher risk of suffering from bulimia
      nervosa. The study concluded that as dancers had a three times higher risk of
      suffering from eating disorders, particularly anorexia nervosa and EDNOS,
      specifically designed services for this population should be considered.

PMID- 24277725
TI  - Metabolism of salvianolic acid A and antioxidant activities of its methylated
      metabolites.
AB  - This study investigated the metabolism of salvianolic acid A (SAA) both in vivo
      and in vitro. Liquid chromatography-mass spectrometry analysis of drug-containing
      rat bile samples and bile samples hydrolyzed by glucuronidase revealed a series
      of methylated conjugates of SAA and its glucuronides, as well as the predominance
      of the methylation pathway of SAA in rats. For the first time, four major
      methylated metabolites present in vivo were prepared for structure
      characterization and bioactivity evaluation using in vitro coincubation systems
      with rat hepatic cytosol protein as the enzyme donor. By using nuclear magnetic
      resonance imaging and other spectroscopic methods, these metabolites were
      unambiguously elucidated as 3-O-methyl-SAA (M1), 3'-O-methyl-SAA (M2), 3,3"-O
      dimethyl-SAA (M3), and 3',3"-O-dimethyl-SAA (M4), respectively. Along with
      results from the enzyme inhibition study, selective formation of these meta-O
      methylated derivatives indicated that catechol O-methyltransferase (COMT) is
      responsible for methylated transformation of SAA. All of these metabolites
      displayed fairly high antioxidant potency against in vitro rat liver lipid
      peroxidation with half-maximal inhibitory concentrations that were much lower
      than those of the positive controls and even SAA. Overall, the results from this
      study demonstrate that SAA is a metabolically unstable compound that undergoes
      rapid methylation metabolism catalyzed by COMT, and these generated O-methylated
      metabolites may be largely responsible for its in vivo pharmacological effects. 

PMID- 24277726
TI  - Timing of xenon-induced delayed postconditioning to protect against spinal cord
      ischaemia-reperfusion injury in rats.
AB  - BACKGROUND: This study was designed to assess the neuroprotective effect of xenon
      induced delayed postconditioning on spinal cord ischaemia-reperfusion injury
      (IRI) and to determine the time of administration for best neuroprotection in a
      rat model of spinal cord IRI. METHODS: Fifty male rats were randomly divided
      equally into a sham group, control group, and three xenon postconditioning groups
      (n=10 per group). The control group underwent spinal cord IRI and immediately
      inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The
      three xenon postconditioning groups underwent the same surgical procedure and
      immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion
      or 1 and 2 h after reperfusion. The sham operation group underwent the same
      surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen.
      Neurological function was assessed using the Basso, Beattie, and Bresnahan score
      at 4, 24, and 48 h of reperfusion. Histological examination was performed using
      Nissl staining and immunohistochemistry, and apoptosis was detected by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling staining. RESULTS: Compared with the control group, the three xenon
      postconditioning groups showed improvements in neurological outcomes, and had
      more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death
      was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon
      treated rats compared with controls. CONCLUSIONS: Xenon postconditioning up to 2
      h after reperfusion provided protection against spinal cord IRI in rats, but the
      greatest neuroprotection occurred with administration of xenon for 1 h at
      reperfusion.

PMID- 24277727
TI  - A rare cause of weight loss.

PMID- 24277728
TI  - Effect of magnesium supplementation and depletion on the onset and course of
      acute experimental pancreatitis.
AB  - BACKGROUND AND OBJECTIVE: High calcium concentrations are an established risk
      factor for pancreatitis. We have investigated whether increasing magnesium
      concentrations affect pathological calcium signals and premature protease
      activation in pancreatic acini, and whether dietary or intraperitoneal magnesium
      administration affects the onset and course of experimental pancreatitis.
      METHODS: Pancreatic acini were incubated with up to 10 mM magnesium; [Ca(2+)](i)
      (fura-2AM) and intracellular protease activation (fluorogenic substrates) were
      determined over 60 min. Wistar rats received chow either supplemented or depleted
      for magnesium (<300 ppm to 30 000 ppm) over two weeks before pancreatitis
      induction (intravenous caerulein 10 ug/kg/h/4 h); controls received 1 ug/kg/h
      caerulein or saline. C57BL6/J mice received four intraperitoneal doses of
      magnesium (NaCl, Mg(2+) 55 192 or 384 mg/kg bodyweight) over 72 h, then
      pancreatitis was induced by up to eight hourly supramaximal caerulein
      applications. Pancreatic enzyme activities, protease activation, morphological
      changes and the immune response were investigated. RESULTS: Increasing
      extracellular Mg(2+) concentration significantly reduced [Ca(2+)](i) peaks and
      frequency of [Ca(2+)](i) oscillations as well as intracellular trypsin and
      elastase activity. Magnesium administration reduced pancreatic enzyme activities,
      oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T
      cells during experimental pancreatitis. Protease activation was found in animals
      fed magnesium-deficient chow-even with low caerulein concentrations that normally
      cause no damage. CONCLUSIONS: Magnesium supplementation significantly reduces
      premature protease activation and the severity of pancreatitis, and antagonises
      pathological [Ca(2+)](i) signals. Nutritional magnesium deficiency increases the
      susceptibility of the pancreas towards pathological stimuli. These data have
      prompted two clinical trials on the use of magnesium in patients at risk for
      pancreatitis.

PMID- 24277730
TI  - Christian Confavreux (1949 - 2013).

PMID- 24277729
TI  - mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous
      neoplasm (IPMN).
AB  - OBJECTIVE: Intraductal papillary mucinous neoplasm (IPMN) consists of four
      epithelial subtypes that correlate with histological grades and risks for
      malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic
      epithelial phenotype that is reactive to premalignant conditions of the upper GI
      tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high
      risk of malignant transformation. DESIGN: mAb Das-1 reactivity was evaluated in
      94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate
      patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and
      pseudocysts (n=4) was analysed by ELISA and western blot. RESULTS:
      Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade
      gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were
      minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was
      significantly higher in high-risk/malignant lesions (p<0.0001) including:
      intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade
      dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and
      pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and
      oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high
      risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from
      low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous
      lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid
      from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity
      (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high
      risk/malignant IPMNs were 89% and 100%, respectively. CONCLUSIONS: mAb Das-1
      reacts with high specificity to tissue and cyst fluid from high-risk/malignant
      IPMNs and thus may help in preoperative clinical risk stratification.

PMID- 24277731
TI  - Gene expression profiling in MS: a fulfilled promise?

PMID- 24277732
TI  - Evoked potentials are of little use in the diagnosis or monitoring of MS: yes.

PMID- 24277733
TI  - Evoked potentials are of little use in the diagnosis or monitoring of MS: no.

PMID- 24277734
TI  - Evoked potentials are of little use in the diagnosis or monitoring of MS:
      commentary.

PMID- 24277735
TI  - Decreased circulating miRNA levels in patients with primary progressive multiple
      sclerosis.
AB  - Emerging evidence underlines the importance of micro(mi)RNAs in the pathogenesis
      of multiple sclerosis (MS). Free-circulating miRNAs were investigated in serum
      from MS patients compared to controls. Statistically significant decreased levels
      of miR-15b, miR-23a and miR-223 were observed in MS patients (p < 0.05). Results
      were validated and replicated in two further independent MS populations. A direct
      correlation between miRNA levels and the EDSS score was determined in PPMS (p <
      0.007). The generalized trend toward miRNA down-regulation could result in over
      expression of target genes involved in disease pathogenesis. Circulating miRNA
      profiling could thus represent a new avenue to identify easily detectable disease
      biomarkers. 

PMID- 24277736
TI  - Social capital to strengthen health policy and health systems.
AB  - This article recounts the development of a model for social capital building
      developed over the course of interventions focused on HIV-related stigma and
      discrimination, safe motherhood and reproductive health. Through further
      engagement with relevant literature, it explores the nature of social capital and
      suggests why undertaking such a process can enhance health policy and programmes,
      advocacy and governance for improved health systems strengthening (HSS) outcomes.
      The social capital process proposed facilitates the systematic and effective
      inclusion of community voices in the health policy process-strengthening
      programme effectiveness as well as health system accountability and governance.
      Because social capital building facilitates communication and the uptake of new
      ideas, norms and standards within and between professional communities of
      practice, it can provide an important mechanism for integration both within and
      between sectors-a process long considered a 'wicked problem' for health policy
      makers. The article argues that the systematic application of social capital
      building, from bonding through bridging into linking social capital, can greatly
      enhance the ability of governments and their partners to achieve their HSS goals.

PMID- 24277737
TI  - Design and experimental application of a novel non-degenerate universal primer
      set that amplifies prokaryotic 16S rRNA genes with a low possibility to amplify
      eukaryotic rRNA genes.
AB  - The deep sequencing of 16S rRNA genes amplified by universal primers has
      revolutionized our understanding of microbial communities by allowing the
      characterization of the diversity of the uncultured majority. However, some
      universal primers also amplify eukaryotic rRNA genes, leading to a decrease in
      the efficiency of sequencing of prokaryotic 16S rRNA genes with possible
      mischaracterization of the diversity in the microbial community. In this study,
      we compared 16S rRNA gene sequences from genome-sequenced strains and identified
      candidates for non-degenerate universal primers that could be used for the
      amplification of prokaryotic 16S rRNA genes. The 50 identified candidates were
      investigated to calculate their coverage for prokaryotic and eukaryotic rRNA
      genes, including those from uncultured taxa and eukaryotic organelles, and a
      novel universal primer set, 342F-806R, covering many prokaryotic, but not
      eukaryotic, rRNA genes was identified. This primer set was validated by the
      amplification of 16S rRNA genes from a soil metagenomic sample and subsequent
      pyrosequencing using the Roche 454 platform. The same sample was also used for
      pyrosequencing of the amplicons by employing a commonly used primer set, 338F
      533R, and for shotgun metagenomic sequencing using the Illumina platform. Our
      comparison of the taxonomic compositions inferred by the three sequencing
      experiments indicated that the non-degenerate 342F-806R primer set can
      characterize the taxonomic composition of the microbial community without
      substantial bias, and is highly expected to be applicable to the analysis of a
      wide variety of microbial communities. 

PMID- 24277738
TI  - Global transcriptional response to heat shock of the legume symbiont
      Mesorhizobium loti MAFF303099 comprises extensive gene downregulation.
AB  - Rhizobia, the bacterial legume symbionts able to fix atmospheric nitrogen inside
      root nodules, have to survive in varied environmental conditions. The aim of this
      study was to analyse the transcriptional response to heat shock of Mesorhizobium
      loti MAFF303099, a rhizobium with a large multipartite genome of 7.6 Mb that
      nodulates the model legume Lotus japonicus. Using microarray analysis, extensive
      transcriptomic changes were detected in response to heat shock: 30% of the
      protein-coding genes were differentially expressed (2067 genes in the chromosome,
      62 in pMLa and 57 in pMLb). The highest-induced genes are in the same operon and
      code for two sHSP. Only one of the five groEL genes in MAFF303099 genome was
      induced by heat shock. Unlike other prokaryotes, the transcriptional response of
      this Mesorhizobium included the underexpression of an unusually large number of
      genes (72% of the differentially expressed genes). This extensive downregulation
      of gene expression may be an important part of the heat shock response, as a way
      of reducing energetic costs under stress. To our knowledge, this study reports
      the heat shock response of the largest prokaryote genome analysed so far,
      representing an important contribution to understand the response of plant
      interacting bacteria to challenging environmental conditions. 

PMID- 24277739
TI  - Large-scale development of gene-associated single-nucleotide polymorphism markers
      for molluscan population genomic, comparative genomic, and genome-wide
      association studies.
AB  - Mollusca is the second most diverse group of animals in the world. Despite their
      perceived importance, omics-level studies have seldom been applied to this group
      of animals largely due to a paucity of genomic resources. Here, we report the
      first large-scale gene-associated marker development and evaluation for a bivalve
      mollusc, Chlamys farreri. More than 21,000 putative single-nucleotide
      polymorphisms (SNPs) were identified from the C. farreri transcriptome. Primers
      and probes were designed and synthesized for 4500 SNPs, and 1492 polymorphic
      markers were successfully developed using a high-resolution melting genotyping
      platform. These markers are particularly suitable for population genomic analysis
      due to high polymorphism within and across populations, a low frequency of null
      alleles, and conformation to neutral expectations. Unexpectedly, high cross
      species transferability was observed, suggesting that the transferable SNPs may
      largely represent ancestral genetic variations that have been preserved
      differentially among subfamilies of Pectinidae. Gene annotations were available
      for 73% of the markers, and 65% could be anchored to the recently released
      Pacific oyster genome. Large-scale association analysis revealed key candidate
      genes responsible for scallop growth regulation, and provided markers for further
      genetic improvement of C. farreri in breeding programmes. 

PMID- 24277740
TI  - Antipneumococcal seroprevalence and pneumococcal carriage during a meningococcal
      epidemic in Burkina Faso, 2006.
AB  - BACKGROUND: To better understand the high incidence of pneumococcal meningitis in
      the African meningitis belt, we conducted a pneumococcal seroprevalence study
      during a meningococcal meningitis epidemic in Western Burkina Faso, March 2006.
      METHODS: In 3 villages experiencing epidemics, we included 624 healthy persons (1
      39 years) by cluster sampling. We determined pneumococcal serum immunoglobulin G
      (IgG) antibody concentrations against 12 serotypes contained in 13-valent
      pneumococcal conjugate vaccine, and evaluated determinants for IgG >= 0.35 MUg/mL
      by multivariate logistic regression. RESULTS: The percentage of subjects with
      serotype-specific IgG concentrations >=0.35 MUg/mL increased with age and was
      similar for the different serotypes: it was 20%-43% among 1-4-year-olds and 56%
      90% among 20-39-year-olds. Prevalence of IgG >= 0.35 MUg/mL against serotype 1
      was up to 71% after age 10 years. During multivariate analyses, determinants of
      IgG concentrations >=0.35 MUg/mL varied by serotype; for 5 and 6 serotypes,
      respectively, female sex (around 2-fold increased odds) and cigarette smoking
      (about 5-fold reduced odds) predicted elevated titers. CONCLUSIONS: Despite a
      substantially higher historical pneumococcal meningitis incidence in Burkina
      Faso, the general population has an antibody seroprevalence against 12
      pneumococcal serotypes similar to that reported from the United Kingdom. The role
      of putatively protective antibody seroprevalence in preventing pneumococcal
      meningitis in the meningitis belt requires more thorough evaluation.

PMID- 24277741
TI  - A FUT2 gene common polymorphism determines resistance to rotavirus A of the P[8]
      genotype.
AB  - Attachment to carbohydrates of the histo-blood group type of several human
      Rotavirus strains (RVA) has recently been described. Synthesis of these ligands
      requires a functional FUT2 enzyme, suggesting that FUT2 null homozygote (ie,
      nonsecretor) individuals may not be recognized by most human RVA strains. Whereas
      such individuals represent 20% of the control population, this retrospective
      study determined that none of 51 patients infected by P[8] rotavirus strains were
      nonsecretors. The lack of alpha1,2fucosylated carbohydrate motifs in the gut
      surface mucosa is thus associated with resistance to symptomatic infection and
      virus attachment to such motifs is essential to the infection process. 

PMID- 24277742
TI  - Low antibody levels to pregnancy-specific malaria antigens and heightened
      cytokine responses associated with severe malaria in pregnancy.
AB  - BACKGROUND:  Pregnant women living in unstable malaria transmission settings may
      develop severe malaria (SM). The pathogenesis of SM in pregnancy is poorly
      understood. METHODS:  To determine whether SM in pregnancy is associated with
      lower malarial antibody responses and higher cytokine responses, plasma samples
      were collected from 121 Sudanese pregnant women of whom 39 were diagnosed with
      SM. Antibodies to pregnancy-specific and non-pregnancy-specific Plasmodium
      falciparum variant surface antigens (VSA) and concentrations of cytokines TNF,
      IFNgamma, IL-1beta, IL-6, IL-8 and IL-10 were measured. RESULTS:  Pregnant women
      with SM demonstrated significantly lower antibody levels to pregnancy-specific
      VSA (P = .020) and higher plasma IFNgamma (P = .020), IL-10 (P = .0002) and IL-6
      levels (P < .0001) than uninfected pregnant women. Concentrations of inflammatory
      cytokines IL-1beta (P = .001), IL-6 (P = .004) and IL-8 (P = .020) were inversely
      correlated with antibodies to VAR2CSA-DBL5 in pregnant women with SM. Lower
      haemoglobin levels and higher parasite densities were associated with lack of
      pregnancy-specific antibodies (P = .028) and higher levels of inflammatory
      cytokines, in particular IL-6 and IL-8. CONCLUSIONS:  Pregnant women with SM lack
      pregnancy-specific malaria immunity, and this correlates with heightened
      inflammatory cytokine concentrations, low haemoglobin levels and high parasite
      density, suggesting that failure of antibody to control parasitaemia may
      contribute to SM pathogenesis.

PMID- 24277743
TI  - Hepatitis C therapy with interferon-alpha and ribavirin reduces CD4 T-cell
      associated HIV-1 DNA in HIV-1/hepatitis C virus-coinfected patients.
AB  - Combined treatment with interferon alpha (IFN-alpha) and ribavirin (RBV) can
      effectively cure HCV infection in a significant proportion of patients, but
      effects of this regimen on cellular reservoirs for human immunodeficiency virus
      type 1 (HIV-1) are unknown. Here, we show that treatment with IFN-alpha/RBV led
      to a moderate but significant and sustained decline of HIV-1 DNA in CD4 T cells
      from HIV-1/hepatitis C virus-coinfected patients receiving highly active
      antiretroviral therapy (n = 12). However, in vitro experiments failed to
      demonstrate an effect of pharmacological doses of IFN-alpha on HIV-1
      reactivation. Together, these data suggest that treatment with IFN-alpha/RBV can
      moderately reduce the reservoir of HIV-1-infected CD4 T cells that persists
      despite suppressive antiretroviral therapy. 

PMID- 24277745
TI  - Identification of collagenase as a critical virulence factor for invasiveness and
      transmission of pathogenic Leptospira species.
AB  - BACKGROUND:  Leptospirosis is a global zoonotic disease. Transmission of
      Leptospira from animals to humans occurs through contact with water contaminated
      with leptospire-containing urine of infected animals. However, the molecular
      basis for the invasiveness of Leptospira and transmission of leptospirosis
      remains unknown. METHODS:  Activity of Leptospira interrogans strain Lai colA
      gene product (ColA) to hydrolyze different collagenic substrates was determined
      by spectrophotometry. Expression and secretion of ColA during infection were
      detected by reverse-transcription quantitative polymerase chain reaction and
      Western blot assay. The colA gene-deleted (DeltacolA) and colA gene-complemented
      (CDeltacolA) mutants were generated to determine the roles of ColA in
      transcytosis in vitro and virulence in hamsters. RESULTS:  Recombinant or native
      ColA hydrolyzed all the tested substrates in which type III collagen was the
      favorite substrate with 2.16 mg/mL Km and 35.6 h(-)(1) Kcat values. Coincubation
      of the spirochete with HUVEC or HEK293 cells directly caused the significant
      elevation of ColA expression and secretion. Compared with wild-type strain,
      DeltacolA mutant displayed much-attenuated transcytosis through HEK293 and HUVEC
      monolayers, and less leptospires in blood, lung, liver, kidney and urine and 25
      fold-decreased 50% lethal dose and milder histopathological injury in hamsters.
      CONCLUSIONS:  The product of colA gene is a collagenase as a crucial virulence
      factor in the invasiveness and transmission of L. interrogans.

PMID- 24277744
TI  - HIV Infection in Uncircumcised Men Is Associated With Altered CD8 T-cell Function
      But Normal CD4 T-cell Numbers in the Foreskin.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected (HIV+) men are more
      susceptible to sexually transmitted infections, and may be superinfected by HIV.
      We hypothesized that HIV induces immune alterations in the foreskin that may
      impact the subsequent acquisition/clearance of genital coinfections. METHODS:
      Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men
      undergoing circumcision. T cells were characterized by flow cytometry,
      immunohistochemistry, and polymerase chain reaction. RESULTS: There was
      substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1
      cells/mm(2); P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs
      33.7/mm(2); P = .67), despite substantial blood depletion (409.0 vs 877.8
      cells/uL; P < .001). While frequencies of foreskin C-C chemokine receptor type
      5(+) (CCR5(+)) T cells, T regulatory cells, and T-helper 17 cells were unaltered
      in HIV+ men, CD8 T-cell production of tumor necrosis factor alpha (TNFalpha) was
      decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men,
      although their frequency and function was reduced compared to the blood.
      CONCLUSIONS: Foreskin CD4 T-cell density and CCR5 expression were not reduced
      during HIV infection, perhaps explaining susceptibility to HIV superinfection.
      Foreskin CD8 T-cell density was increased, but decreased production of TNFalpha
      may enhance susceptibility to genital coinfections in HIV+ men.

PMID- 24277747
TI  - Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by
      increasing cellular immunity and autoimmunity.
AB  - STUDY QUESTION: Do women with recurrent pregnancy losses (RPL) and low vitamin D
      have increased prevalence of auto- and cellular immune abnormalities when
      compared with women with RPL who have normal vitamin D, and does vitamin D have
      any effect on cellular immunity in vitro? SUMMARY ANSWER: A high proportion of
      women with RPL have vitamin D deficiency and the risk of auto- and cellular
      immune abnormalities is increased in women with RPL and vitamin D deficiency.
      WHAT IS KNOWN ALREADY: Vitamin D deficiency in pregnant women is associated with
      increased risk of obstetrical complications such as pre-eclampsia, bacterial
      vaginosis associated preterm delivery, gestational diabetes mellitus and small
      for-gestational age births. STUDY DESIGN, SIZE, DURATION: A retrospective cross
      sectional study of 133 women with RPL who were enrolled in a 2-year period,
      together with laboratory experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Women with three or more consecutive spontaneous abortions prior to 20 weeks of
      gestation who were enrolled at the University clinic. Serum vitamin D level,
      cellular activity and autoimmune parameters in vivo and in vitro were measured.
      MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-three out of 133 women (47.4%) had low
      vitamin D (<30 ng/ml). The prevalence of antiphospholipid antibody (APA) was
      significantly higher in low vitamin D group (VDlow) (39.7%) than in the normal
      vitamin D group (VDnl) (22.9%) (P< 0.05) and the adjusted odds ratio (OR) for APA
      in VDlow was 2.22 with the 95% confidence interval (CI) of 1.0-4.7. The
      prevalence of antinuclear antigen antibody (VDlow versus VDnl; 23.8% versus
      10.0%, OR 2.81, 95% CI 1.1-7.4), anti-ssDNA (19.0% versus 5.7%, OR 3.76, 95% CI
      1.1-12.4) and thyroperoxidase antibody (33.3% versus 15.7%, OR 2.68, 95% CI 1.2
      6.1) was significantly higher in VDlow than those of VDnl (P < 0.05 each).
      Peripheral blood CD19(+) B and CD56(+) NK cell levels and NK cytotoxicity at
      effector to target cell (E:T) ratio of 25:1 were significantly higher in VDlow
      when compared with those of VDnl (P < 0.05 each). Reduction (%) of NK
      cytotoxicity (at E:T ratio of 50:1 and 25:1) by IgG (12.5 mg/dl) was
      significantly lower in VDlow than those of VDnl (P < 0.05, P < 0.01,
      respectively). There were no differences in Th1/Th2 ratios between VDlow and
      VDnl. When vitamin D3 was added in NK cytotoxicity assay in vitro, NK
      cytotoxicity at E:T ratio of 50:1 was significantly suppressed with 10 nMol/L
      (nM) (11.9 +/- 3.3%) and 100 nM (10.9 +/- 3.7%) of vitamin D3 when compared with
      controls (15.3 +/- 4.7%) (P < 0.01 each). TNF-alpha/IL-10 expressing CD3(+)/4(+)
      cell ratios were significantly decreased with 100 nM of vitamin D3 (31.3 +/- 9.4,
      P < 0.05) when compared with controls (40.4 +/- 11.3) in vitro. Additionally, INF
      gamma/IL-10 expressing CD3(+)/4(+) cell ratio was significantly decreased with
      100 nM of vitamin D3 (12.1 +/- 4.0, P < 0.05) when compared with controls (14.8
      +/- 4.6). IFN-gamma and TNF-alpha secretion from NK cells were significantly
      decreased (P < 0.01 each), and IL-10, IL-1beta, vascular endothelial growth
      factor and granulocyte colony stimulating factor levels were significantly
      increased (P < 0.01 each) with vitamin D3 100 nM when compared with those of
      controls. LIMITATIONS, REASONS FOR CAUTION: The prevalence of vitamin D
      deficiency in women with RPL in this study is open to a possible type I error
      since women with vitamin D supplementation were excluded from this study. WIDER
      IMPLICATIONS OF THE FINDINGS: Assessment of vitamin D level is recommended in
      women with RPL. Vitamin D supplementation should be explored further as a
      possible therapeutic option for RPL. STUDY FUNDING/COMPETING INTEREST(S): This
      work was supported by the intramural funding from Department of Microbiology and
      Immunology, Chicago Medical School at Rosalind Franklin University of Medicine
      and Science. None of the authors has any conflict of interest to declare. TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 24277748
TI  - Uterine peristalsis exerts control over fluid migration after mock embryo
      transfer.
AB  - STUDY QUESTION: What is the effect of uterine peristalsis on fluid migration
      after mock embryo transfer? SUMMARY ANSWER: Uterine peristaltic wave frequency
      was positively correlated with the distance that fluid moved after it was
      deposited in the uterine cavity. WHAT IS KNOWN ALREADY: Embryos have been found
      outside the uterine cavity after embryo transfer. It has been suggested that
      uterine contractions expelled these embryos. STUDY DESIGN, SIZE, DURATION: A
      prospective cohort study of a total of 112 infertile women was conducted between
      March 2013 and May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Uterine
      peristaltic activity was assessed before and after a mock embryo transfer, in
      which 20 ul of ultrasound contrast agent was placed in the uterine lumen 3 days
      after ovulation in a natural cycle. The movement of this fluid was measured by
      ultrasound at 0, 15 and 30 min after placement. MAIN RESULTS AND THE ROLE OF
      CHANCE: The uterine peristaltic wave frequency was significantly higher after
      than before mock transfer (3.06 +/- 0.99 versus 2.24 +/- 0.74, P < 0.01). At the
      conclusion of the 30-min monitoring period, the fluid had remained in place (N =
      94), leaked into the cervix (N = 5), or moved into the Fallopian tubes or the
      cornua of the uterus (N = 11). The fluid movement was positively correlated with
      uterine peristaltic wave frequencies before (r = 0.518, P < 0.01) and after
      embryo transfer (r = 0.371, P < 0.01) and uterine peristaltic wave frequency was
      significantly higher both before and after embryo transfer in cases where the
      fluid was extruded. LIMITATIONS, REASONS FOR CAUTION: Mock embryo transfer was
      performed in the luteal phase of a natural cycle instead of a controlled ovarian
      stimulation cycle. The endometrial environment and uterine peristalsis may be
      different in a stimulated cycle. WIDER IMPLICATIONS OF THE FINDINGS: Uterine
      peristalsis exerts control over embryo migration and could adversely affect the
      chances of pregnancy if the wave frequency is too high. It could be used as a
      predictor of uterine irritability before embryo transfer. STUDY FUNDING/COMPETING
      INTEREST(S): The authors declare that they have not received any particular study
      funding and do not have competing interests in this study.

PMID- 24277749
TI  - Comparison of quality of life based on surgical technique in patients with breast
      cancer.
AB  - OBJECTIVE: More than 80% of women with breast cancer survive for more than 5
      years; quality of life is an important issue in these patients. The aim of this
      study was to assess differences in quality of life among patients who have
      undergone breast-conserving surgery, total mastectomy and immediate
      reconstruction after total mastectomy. METHODS: A cross-sectional study was
      conducted during follow-up visits. Women who underwent surgical treatment at
      least 2 years prior were eligible if they were aged 20-70 years and had a
      diagnosis of breast cancer (Stages 0-III). Quality of life was evaluated based on
      the European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30 and European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire breast cancer-specific module, Rosenberg
      Self-esteem Scale, Beck Depression Index, Body Image Scale and sexual scale of
      the Cancer Rehabilitation Evaluation System. RESULTS: A total of 407 patients
      completed the questionnaires; 254 were treated with breast-conserving surgery,
      122 with total mastectomy and 31 with reconstruction after total mastectomy. The
      mean period between surgery and the survey was 49 months. Women in the breast
      conserving surgery group showed better outcomes than women in the total
      mastectomy and reconstruction after total mastectomy groups with respect to
      emotional-social function, nausea/vomiting, financial difficulty, body image, arm
      symptoms and self-esteem. Patients in the reconstruction after total mastectomy
      group had significantly better outcomes on the sexual scale of the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      breast cancer-specific module and arm symptoms than the total mastectomy group.
      CONCLUSIONS: Quality of life was better in the breast-conserving surgery group
      than in the total mastectomy or reconstruction after total mastectomy groups, and
      the total mastectomy and reconstruction after total mastectomy groups had similar
      quality of life. Efforts to evaluate and improve the quality of life of patients
      with breast cancer should be continued.

PMID- 24277750
TI  - MicroRNA-338-3p inhibits colorectal carcinoma cell invasion and migration by
      targeting smoothened.
AB  - OBJECTIVE: To investigate the regulative effect of microRNA-338-3p on colorectal
      carcinoma cell invasion and migration. METHODS: The microRNA-338-3p expression
      pattern of colorectal carcinoma tissues and cell lines was detected by real-time
      reverse transcriptase polymerase chain reaction. The protein level of smoothened
      was detected by western blot analysis. Furthermore, colorectal carcinoma cells
      were pretreated with or without anti-smoothened-small interfering ribonucleic
      acid prior to the addition of pre-microRNA-338-3p or anti-microRNA-338-3p. The
      status of colorectal carcinoma cell invasion and that of migration were detected
      by transwell assay and wound healing assay, respectively. RESULTS: The expression
      of microRNA-338-3p was significantly down-regulated in colorectal carcinoma
      tissues in comparison with those in the adjacent non-tumorous tissues, and the
      value was negatively related to advanced tumor, node, metastasis stage and local
      invasion. The expression of microRNA-338-3p in colorectal carcinoma cells
      transfected with pre-microRNA-338-3p p was significantly increased. Furthermore,
      over-expression of microRNA-338-3p inhibited the expression of smoothened protein
      in colorectal carcinoma cells, which showed obviously suppressed invasion and
      migration ability. The expression of microRNA-338-3p in colorectal carcinoma
      cells transfected with anti-microRNA-338-3p was significantly decreased.
      Moreover, the down-regulated expression of microRNA-338-3p caused the up
      regulated expression of smoothened protein in colorectal carcinoma cells, which
      showed significantly enhanced invasion and migration ability. However, anti
      smoothened-small interfering ribonucleic acid largely, but not completely,
      reversed the effects induced by blockage of microRNA-338-3p, suggesting that the
      regulative effect of microRNA-338-3p on colorectal carcinoma cell invasion and
      migration was indeed mediated by smoothened. Additionally, smoothened was
      identified as a direct target of microRNA-338-3p by luciferase assay.
      CONCLUSIONS: MicroRNA-338-3p could inhibit colorectal carcinoma cell invasion and
      migration by inhibiting smoothened expression.

PMID- 24277751
TI  - Pulmonary inflammatory myofibroblastic tumor harboring EML4-ALK fusion gene.
AB  - Inflammatory myofibroblastic tumor is a rare tumor deriving from mesenchymal
      tissue. Approximately 50% of inflammatory myofibroblastic tumors harbor an
      anaplastic lymphoma kinase fusion gene. Pulmonary inflammatory myofibroblastic
      tumors harboring tropomyosin3-anaplastic lymphoma kinase or protein tyrosine
      phosphatase receptor-type F polypeptide-interacting protein-binding protein 1
      anaplastic lymphoma kinase have been reported previously. However, it has not
      been reported that inflammatory myofibroblastic tumors harbor echinoderm
      microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene
      which is considered to be very specific to lung cancers. A few tumors harboring
      echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase
      fusion gene other than lung cancers have been reported and the tumors were all
      carcinomas. A 67-year-old man had been followed up for a benign tumor for
      approximately 3 years before the tumor demonstrated malignant transformation.
      Lobectomy and autopsy revealed that an inflammatory myofibroblastic tumor
      harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma
      kinase fusion gene had transformed into an undifferentiated sarcoma. This case
      suggests that echinoderm microtubule-associated protein-like 4-anaplastic
      lymphoma kinase fusion is an oncogenic event in not only carcinomas but also
      sarcomas originating from stromal cells. 

PMID- 24277752
TI  - Serelaxin: insights into its haemodynamic, biochemical, and clinical effects in
      acute heart failure.

PMID- 24277753
TI  - Catch me if you can.

PMID- 24277754
TI  - The enigmatic search for optimal DAPT duration.

PMID- 24277755
TI  - Ovarian cancer familial relative risks by tumour subtypes and by known ovarian
      cancer genetic susceptibility variants.
AB  - BACKGROUND: Family history is one of the most important risk factors for
      epithelial ovarian cancer (EOC). Little is known, however, on how EOC familial
      relative risks (FRRs) vary by factors such as tumour subtype or the combined
      effects of common EOC susceptibility alleles. In addition, no data currently
      exist on the FRRs associated with EOC after exclusion of BRCA1 or BRCA2 mutation
      carriers. METHODS: EOC FRRs were computed from observed EOCs in relatives of 1548
      patients with EOC recruited between 1999 and 2010 from a population-based cohort
      study with known BRCA1 and BRCA2 mutation status and tumour subtype, compared
      with the number expected in the general population. RESULTS: The EOC FRR to all
      first-degree relatives was estimated to be 2.96 (95% CI 2.35 to 3.72) but there
      was no evidence of difference in the FRRs for mothers, sisters and daughters.
      There was significant evidence that the FRR for relatives of patients with EOC
      diagnosed under age 50 years is higher than that for older patients (4.72 (95% CI
      3.21 to 6.95) and 2.53 (95% CI 1.91 to 3.35), p-diff=0.0052) and a suggestion
      that the FRR in relatives of patients with serous disease is higher than that for
      non-serous tumours (3.64 (95% CI 2.72 to 4.87) and 2.25 (95% CI 1.56 to 3.26), p
      diff=0.0023). The FRR to relatives of cases without a deleterious mutation in
      BRCA1 or BRCA2 was estimated to be over twice that of the general population
      (2.24 (95% CI 1.71 to 2.94)). BRCA1 and BRCA2 mutations were estimated to account
      for about 24% of the EOC FRR to first-degree relatives. FRRs were found to
      increase with increasing polygenic risk score of the index patient, although the
      trend was not significant. CONCLUSIONS: These estimates could be useful in the
      counselling of relatives of patients with ovarian cancer.

PMID- 24277756
TI  - Radiopharmaceutical therapy of patients with metastasized melanoma with the
      melanin-binding benzamide 131I-BA52.
AB  - The performance of cytotoxic drugs is defined by their selectivity of uptake and
      action in tumor tissue. Recent clinical responses achieved by treating metastatic
      malignant melanoma with therapeutic modalities based on gene expression profiling
      showed that malignant melanoma is amenable to systemic treatment. However, these
      responses are not persistent, and complementary targeted treatment strategies are
      required for malignant melanoma. METHODS: Here we provide our experience with
      different labeling procedures for the radioiodination of benzamides and report on
      initial dosimetry data and the first therapeutic application of (131)I-BA52, a
      novel melanin-binding benzamide in patients with metastatic malignant melanoma.
      Twenty-six adults with histologically documented metastasized malignant melanoma
      received a single dose of 235 +/- 62 MBq of (123)I-BA52 for planar and SPECT/CT
      imaging. Nine patients were selected for radionuclide therapy and received a
      median of 4 GBq (minimum, 0.51 GBq; maximum, 6.60 GBq) of the beta-emitting
      radiopharmaceutical (131)I-BA52. RESULTS: A trimethyltin precursor-based
      synthesis demonstrated high radiochemical yields in the large-scale production of
      radioiodinated benzamides required for clinical application. (123)I-BA52 showed
      specific uptake and long-term retention in tumor tissue with low transient uptake
      in the excretory organs. In tumor tissue, a maximum dose of 12.2 Gy per GBq of
      (131)I-BA52 was calculated. The highest estimated dose to a normal organ was
      found for the lung (mean, 3.1 Gy/GBq). No relevant acute or mid-term toxicity was
      observed with the doses administered until now. Even though dosimetric
      calculations reveal that the doses applied in this early phase of clinical
      application can be significantly increased, we observed antitumor effects with
      follow-up imaging, and single patients of the benzamide-positive cohort of
      patients (3/5 of the patients receiving a dose > 4.3 GBq) demonstrated a
      surprisingly long survival of more than 2 y. CONCLUSION: These data indicate that
      systemic radionuclide therapy using (131)I-BA52 as a novel approach for the
      therapy of malignant melanoma is of considerable potential. Future trials should
      be done to enhance the precision of dosimetry, validate the maximum tolerable
      dose, and evaluate the effectiveness of the treatment in a prospective manner.

PMID- 24277761
TI  - Role of hyperleptinemia in the regulation of blood pressure and cardiac function.

PMID- 24277762
TI  - European Society of Hypertension and European Society of Cardiology guidelines
      and the muted enthusiasm for home blood pressure monitoring.

PMID- 24277764
TI  - Celebrating 35 years of success.

PMID- 24277763
TI  - Measurement error corrected sodium and potassium intake estimation using 24-hour
      urinary excretion.
AB  - Epidemiological studies of the association of sodium and potassium intake with
      cardiovascular disease risk have almost exclusively relied on self-reported
      dietary data. Here, 24-hour urinary excretion assessments are used to correct the
      dietary self-report data for measurement error under the assumption that 24-hour
      urine recovery provides a biomarker that differs from usual intake according to a
      classical measurement model. Under this assumption, dietary self-reports
      underestimate sodium by 0% to 15%, overestimate potassium by 8% to 15%, and
      underestimate sodium/potassium ratio by ~20% using food frequency questionnaires,
      4-day food records, or three 24-hour dietary recalls in Women's Health Initiative
      studies. Calibration equations are developed by linear regression of log
      transformed 24-hour urine assessments on corresponding log-transformed self
      report assessments and several study subject characteristics. For each self
      report method, the calibration equations turned out to depend on race and age and
      strongly on body mass index. After adjustment for temporal variation, calibration
      equations using food records or recalls explained 45% to 50% of the variation in
      (log-transformed) 24-hour urine assessments for sodium, 60% to 70% of the
      variation for potassium, and 55% to 60% of the variation for sodium/potassium
      ratio. These equations may be suitable for use in epidemiological disease
      association studies among postmenopausal women. The corresponding signals from
      food frequency questionnaire data were weak, but calibration equations for the
      ratios of sodium and potassium/total energy explained ~35%, 50%, and 45% of log
      biomarker variation for sodium, potassium, and their ratio, respectively, after
      the adjustment for temporal biomarker variation and may be suitable for cautious
      use in epidemiological studies. Clinical Trial Registration- URL:
      www.clinicaltrials.gov. Unique identifier: NCT00000611. 

PMID- 24277766
TI  - Repair of complete atrioventricular septal defect: close to the moon? From giant
      leap for the medical community to small steps for our patients.

PMID- 24277765
TI  - Is flow-mediated dilation nitric oxide mediated?: A meta-analysis.
AB  - Flow-mediated dilation (FMD) is a noninvasive index of endothelial function and
      vascular health in humans. Studies examining the role of nitric oxide (NO) are
      not conclusive. In this article, we quantified the contribution of NO in FMD of
      conduit arteries and explored the effect of the protocol (ie, distal cuff, ~5
      minute ischemia) and method of analysis (ie, automated and continuous edge
      detection) on the NO dependency of this test. A systematic review and 3-stage
      meta-analysis of published crossover studies that measured FMD under local
      infusion of saline or the NO synthase blocker N(G)monomethyl-L-arginine (L-NMMA)
      was undertaken. Twenty studies met the inclusion criteria for stage 1 (374
      individual comparisons). The meta-analyzed outcome was the difference in FMD
      between infusion of saline (ie, FMD(saline)) and NO synthase blocker (ie, FMD(L
      NMMA)). Overall, FMD(saline) was 8.2% (95% confidence interval [CI], 6.8%-9.6%)
      compared with FMD(L-NMMA) of 3.7% (95% CI, 3.1%-4.3%; P<0.001). Stage 2 analysis
      focused on studies that used the most commonly adopted approach in healthy
      volunteers (ie, distal cuff placement, ~5-minute occlusion), which similarly
      revealed a significant NO contribution to FMD (FMD(saline), 6.5% [95% CI, 5.7%
      7.3%]; FMD(L-NMMA), 0.9% [95% CI, 0.5%-1.3%]; P<0.001). Stage 3 meta-analyzed the
      studies that adopted the commonly adopted approach and automated, continuous
      method of analysis, which also revealed a significant contribution of NO to the
      FMD (FMD(saline), 6.9% [95% CI, 6.0%-7.8%]; FMD(L-NMMA), 2.4% [95% CI, 1.1%
      3.7%]; P<0.001). This comprehensive analysis demonstrates that FMD of conduit
      arteries in humans is, at least in part, mediated by NO.

PMID- 24277767
TI  - Transposition of the great arteries with ventricular septal defect and left
      ventricular outflow tract obstruction: how to choose in the surgical
      armamentarium?

PMID- 24277768
TI  - Direct implantation of scimitar vein to the left atrium via sternotomy: a
      reappraisal.
AB  - OBJECTIVES: There is no consensus about optimal surgical technique for the repair
      of scimitar vein, an anomalous right pulmonary venous connection to the inferior
      vena cava. Our current experience with a direct anastomosis of the scimitar vein
      to the left atrium via sternotomy may be shared with other centres, but has not
      been widely published. METHODS: Six consecutive patients (age 6 months to 17
      years, mean 5 years) operated on in 2009-12 were retrospectively reviewed.
      Through median sternotomy and with cardiopulmonary bypass, the mobilized
      anomalous right pulmonary vein was brought through a large pericardial opening
      posterior to the right phrenic nerve and anastomosed onto the right side of the
      posterior left atrium with access via an existing or a surgically created atrial
      septal defect. RESULTS: Five patients had primary venous repair and one had a
      previous failed repair using an intra-atrial baffle. The median cardiopulmonary
      bypass and cross-clamp times were 88 and 38 min, respectively. The median
      ventilator time was 1 day and the median stay at the intensive care unit 3.5
      days. There were no deaths within a median follow-up of 28 months (range 8-41
      months), nor reoperations or instances of pulmonary venous obstruction.
      CONCLUSIONS: Anatomic repair of the scimitar vein based on reimplantation onto
      the left atrium via sternotomy is conceptually appealing. The surgery results in
      a safe and reliable repair in patients with a wide age spectrum. Durability needs
      on-going assessment in longer-term follow-up.

PMID- 24277769
TI  - An introduction to latent variable mixture modeling (part 1): overview and cross
      sectional latent class and latent profile analyses.
AB  - OBJECTIVE: Pediatric psychologists are often interested in finding patterns in
      heterogeneous cross-sectional data. Latent variable mixture modeling is an
      emerging person-centered statistical approach that models heterogeneity by
      classifying individuals into unobserved groupings (latent classes) with similar
      (more homogenous) patterns. The purpose of this article is to offer a
      nontechnical introduction to cross-sectional mixture modeling. METHOD: An
      overview of latent variable mixture modeling is provided and 2 cross-sectional
      examples are reviewed and distinguished. RESULTS: Step-by-step pediatric
      psychology examples of latent class and latent profile analyses are provided
      using the Early Childhood Longitudinal Study-Kindergarten Class of 1998-1999 data
      file. CONCLUSIONS: Latent variable mixture modeling is a technique that is useful
      to pediatric psychologists who wish to find groupings of individuals who share
      similar data patterns to determine the extent to which these patterns may relate
      to variables of interest.

PMID- 24277770
TI  - An introduction to latent variable mixture modeling (part 2): longitudinal latent
      class growth analysis and growth mixture models.
AB  - OBJECTIVE: Pediatric psychologists are often interested in finding patterns in
      heterogeneous longitudinal data. Latent variable mixture modeling is an emerging
      statistical approach that models such heterogeneity by classifying individuals
      into unobserved groupings (latent classes) with similar (more homogenous)
      patterns. The purpose of the second of a 2-article set is to offer a nontechnical
      introduction to longitudinal latent variable mixture modeling. METHODS: 3 latent
      variable approaches to modeling longitudinal data are reviewed and distinguished.
      RESULTS: Step-by-step pediatric psychology examples of latent growth curve
      modeling, latent class growth analysis, and growth mixture modeling are provided
      using the Early Childhood Longitudinal Study-Kindergarten Class of 1998-1999 data
      file. CONCLUSIONS: Latent variable mixture modeling is a technique that is useful
      to pediatric psychologists who wish to find groupings of individuals who share
      similar longitudinal data patterns to determine the extent to which these
      patterns may relate to variables of interest.

PMID- 24277771
TI  - Breast cancer in young women in Latin America: an unmet, growing burden.
AB  - Breast cancer (BC) is the leading cause of malignancy-related deaths among women
      aged <=45 years. There are unexplored and uncertain issues for BC in this
      particular group in Latin America. The aim of this study is to evaluate BC
      incidence and mortality among young women and related clinicopathological and
      survivorship aspects in this region. MATERIALS AND METHODS: Data were obtained
      from Globocan 2008 and the International Agency for Research on Cancer's Cancer
      Incidence in Five Continents series plus databases. We requested collaboration
      from the 12 different national cancer institutes in Latin America through SLACOM,
      the Latin American and Caribbean Society of Medical Oncology, and conducted a
      systematic literature review to obtain local data regarding the prevalence of BC
      among young women and their characteristics, outcomes, and survivorship-related
      issues. RESULTS: BC incidence and mortality proportions for Latin American women
      aged <44 years were higher when compared with those of developed countries (20%
      vs. 12% and 14% vs. 7%, respectively). We found only a few Latin American series
      addressing this topic, and prevalence varied between 8% and 14%. Stage II and III
      disease, high histological grade, and triple-negative and HER2 BC were features
      frequently observed among young Latin American BC patients. CONCLUSION: The
      rising incidence and mortality of BC in young Latin American women is a call to
      action in the region. It is necessary to monitor the epidemiological and clinical
      data through reliable cancer registries and to consider the implementation of
      protocols for education of patients and health professionals. This unmet, growing
      burden must be considered as a top priority of the national programs in the fight
      against BC, and models of specialized units should be implemented for this
      particular group of patients to provide better care for this emergent challenge.

PMID- 24277772
TI  - Adjuvant therapy for a 3.9-cm adenocarcinoma of the lung.
AB  - After routine staging tests, including a FDG-PET scan and MRI of the brain, a 59
      year-old mother of four, never smoker, undergoes uncomplicated right lower
      lobectomy of the lung to remove a 3.9 cm adenocarcinoma with visceral pleural
      invasion (pIB,T2N0M0). Should she receive adjuvant chemotherapy? If so, what
      drug, dose, and schedule?

PMID- 24277773
TI  - Gestational age-specific reference ranges from different laboratories misclassify
      pregnant women's thyroid status: comparison of two longitudinal prospective
      cohort studies.
AB  - OBJECTIVES: Correct interpretation of thyroid status during pregnancy is vital to
      secure fetal development. Pregnancy-related changes in maternal thyroid status
      necessitate the use of gestational age-specific reference ranges. In this study,
      we investigated between-laboratory reproducibility of thyroid reference ranges in
      pregnant women. DESIGN: Comparison of two longitudinal prospective cohort studies
      including 255 (cohort 1) and 101 (cohort 2) healthy antibody-negative Danish
      pregnant women attending prenatal care at Copenhagen University Hospital.
      METHODS: Different immunoassays were used to measure thyroid hormone levels in
      the two cohorts. Thyroid hormone reference ranges were established for every 5
      weeks of gestation. Differences between cohorts were explored through mixed-model
      repeated measures regression analyses. By applying reference ranges from one
      cohort to the other, the proportion of women who would be misclassified by doing
      so was investigated. RESULTS: TSH increased and free thyroxine (FT4) decreased as
      pregnancy progressed. Results indicated highly significant differences between
      cohorts in free triiodothyronine (F=21.3, P<0.001) and FT4 (F=941, P<0.001). TSH
      levels were comparable (P=0.09). Up to 90.3% of the women had FT4 levels outside
      their laboratory's nonpregnant reference range, and up to 100% outside the other
      cohort's gestational-age-specific reference ranges. Z-score-based reference
      ranges markedly improved comparison between cohorts. CONCLUSION: Even in the same
      region, the use of gestational-age-specific reference ranges from different
      laboratories led to misclassification. Up to 100% of maternal FT4 levels fell
      outside the other cohort's reference range despite similar TSH levels. In
      clinical practice, thyroid testing of pregnant women without adding method
      specificity to gestational age-dependent reference ranges will compromise patient
      safety.

PMID- 24277774
TI  - Repeating the past: prevention focus motivates repetition, even for unethical
      decisions.
AB  - Prevention-focused individuals are motivated to maintain the status quo. Given
      this, we predicted that individuals with a strong prevention focus, either as a
      chronic predisposition or situationally induced, would treat their initial
      decision on how to behave on a first task as the status quo and would thus be
      motivated to repeat that decision on a subsequent task-even for decisions that
      were ethically questionable. Results from five studies supported this prediction
      in multiple ethical domains: whether or not to overstate performance (Studies 1,
      2a, and 2b), whether or not to disclose disadvantageous facts (Study 3), and
      whether or not to pledge a donation (Study 4). The prevention-repetition effect
      was observed both when the initial and subsequent decisions were in the same
      domain (Studies 1-3) and when they were in different domains (Study 4).
      Alternative accounts for this effect, such as justification for the initial
      decision and preference for consistency, were ruled out (Study 2b). 

PMID- 24277775
TI  - Out smoking on the big screen: tobacco use in LGBT movies, 2000-2011.
AB  - OBJECTIVE: Lesbian, gay, bisexual and transgender (LGBT) people have
      significantly higher smoking prevalence than heterosexual people in the U.S.A.
      The reasons for this disparity remain unclear. Tobacco use in movies has a
      substantial influence on tobacco use behaviours, particularly among youth. Yet,
      no research has examined tobacco use in movies for LGBT audiences or containing
      LGBT characters. METHODS: We identified 81 U.S. movies from 2000 to 2011 with a
      theatre release and with LGBT themes or characters. We then selected a random
      sample of these movies (n=45) for quantitative content analysis to examine the
      proportion of movies with depictions of tobacco use and the number of occurrences
      of tobacco use. RESULTS: Tobacco use was depicted in 87% (95% CI 80% to 94%) of
      movies with an average of four occurrences of tobacco use per hour (95% CI 3 to
      5). Only 15% (95% CI 8% to 23%) of movies and 3% of all depictions of tobacco use
      conveyed any harms of tobacco use. CONCLUSIONS: Viewers of movies with LGBT
      themes or characters are exposed, on average, to one depiction of tobacco use for
      every 15 min of movie run-time. As a major component of the entertainment media
      environment, movies may contribute to smoking among LGBT people.

PMID- 24277776
TI  - Exploring the impact of patient and public involvement in a cancer research
      setting.
AB  - An enduring theme in the literature exploring patient and public involvement
      (PPI) in research has been the focus on evaluating impact, defined usually in
      terms of participants' practical contribution to enhancing research processes. By
      contrast, there has been less emphasis on the perspectives and experiences of
      those involved in PPI. Drawing on qualitative data with people involved in the
      National Cancer Research Network in the United Kingdom, we report on what
      motivated participants to get involved and their experiences of involvement in
      this setting. We highlight how those involved in PPI often espoused the notion of
      the "good citizen," with PPI in research being a natural extension of their wider
      civic interests. However, our findings also highlight how PPI was an important
      resource, utilized by participants to make sense of living with chronic illness.
      We suggest that PPI in research also offers spaces for the reconfiguration of
      self and identity. 

PMID- 24277777
TI  - Chronic kidney disease, albuminuria and socioeconomic status in the Health
      Surveys for England 2009 and 2010.
AB  - BACKGROUND: Renal replacement therapy rates are inversely related to
      socioeconomic status (SES) in developed countries. The relationship between
      chronic kidney disease (CKD) and SES is less clear. This study examined the
      relationships between SES and CKD and albuminuria in England. METHODS: Data from
      the Health Survey for England 2009 and 2010 were combined. The prevalence of CKD
      3-5 and albuminuria was calculated, and logistic regression used to determine
      their association with five individual-level measures and one area-level measure
      of SES. RESULTS: The prevalence of CKD 3-5 was 5.2% and albuminuria 8.0%. Age-sex
      adjusted CKD 3-5 was associated with lack of qualifications [odds ratio (OR) 2.27
      (95% confidence interval 1.40-3.69)], low income [OR 1.50 (1.02-2.21)] and
      renting tenure [OR 1.36 (1.01-1.84)]. Only tenure remained significant in fully
      adjusted models suggesting that co-variables were on the causal pathway.
      Albuminuria remained associated with several SES measures on full adjustment: low
      income [OR 1.55 (1.14-2.11)], no vehicle [OR 1.38 (1.05-1.81)], renting [OR 1.31
      [1.03-1.67)] and most deprived area-level quintile [OR 1.55 (1.07-2.25)].
      CONCLUSIONS: CKD 3-5 and albuminuria were associated with low SES using several
      measures. For albuminuria this was not explained by known measured causal
      factors.

PMID- 24277778
TI  - Food for thought: pilot randomized controlled trial of lay health trainers
      supporting dietary change to reduce cardiovascular disease in deprived
      communities.
AB  - BACKGROUND: Cardiovascular disease (CVD) accounts for 30% of UK deaths. It is
      associated with modifiable lifestyle factors, including insufficient consumption
      of fruit and vegetables (F&V). Lay health trainers (LHTs) offer practical support
      to help people develop healthier behaviour and lifestyles. Our two-group pilot
      randomized controlled trial (RCT) investigated the effectiveness of LHTs at
      promoting a heart-healthy lifestyle among adults with at least one risk factor
      for CVD to inform a full-scale RCT. METHODS: Eligible adults (aged 21-78 years),
      recruited from five practices serving deprived populations, were randomized to
      health information leaflets plus LHTs' support for 3 months (n = 76) versus
      health information leaflets alone (n = 38). RESULTS: We recruited 114
      participants, with 60% completing 6 month follow-up. Both groups increased their
      self-reported F&V consumption and we found no evidence for LHTs' support having
      significant added impact. Most participants were relatively less deprived, as
      were the LHTs we were able to recruit and train. CONCLUSIONS: Our pilot
      demonstrated that an LHT's RCT whilst feasible faces considerable challenges.
      However, to justify growing investment in LHTs, any behaviour changes and
      sustained impact on those at greatest need should be demonstrated in an
      independently evaluated, robust, fully powered RCT.

PMID- 24277779
TI  - Migration and determinants of health: clinical epidemiological characteristics of
      migrants in Malta (2010-11).
AB  - BACKGROUND: Over recent years Malta has experienced a growing influx of migrants
      from Africa. With the aim of defining demographic characteristics and assessing
      the prevalence of conditions of public health significance among asylum seekers
      in Malta, a clinical research study was implemented in the framework of the
      European Union project 'Mare nostrum'. METHODS: From August 2010 to June 2011 a
      dermatologist and an infectious diseases specialist performed general and
      specialist health assessment of migrants hosted in open centres. RESULTS:
      Migrants included in the study were 2216, 82.7% were males, their mean age was 25
      years and 70.1% were from Somalia. Out of the total females, 42.5% had undergone
      some type of Female Genital Mutilation/Cutting. A total of 5077 diagnoses were
      set, most common were skin diseases (21.9%), respiratory diseases (19.8%) and
      gastro-enteric diseases (14.2%), whereas 31% of migrants reported good health
      conditions. CONCLUSIONS: Immigrants have a lower morbidity burden compared with
      their fellow countrymen living in the origin country. However, living conditions
      during the journey, in transit countries and after arrival can influence their
      health status. The present study provides a comprehensive picture of this growing
      population that is in need for health promotion, mental health services and fair
      policy planning.

PMID- 24277780
TI  - The outcome of a cohort of tuberculin-positive predominantly South Asian new
      entrants aged 16-34 to the UK: Blackburn 1989-2001.
AB  - SETTING: Blackburn, Hyndburn and Ribble Valley Local Government areas of England
      and Wales, the former a high tuberculosis (TB) prevalence district. BACKGROUND:
      The incidence of tuberculosis in new entrants aged 16-34 with positive tuberculin
      skin tests but normal chest X-rays after initial entry is not definitely known,
      and was previously estimated from cross-sectional national surveys and derived
      data for the 2006 and 2011 NICE economic appraisals of new entrant TB screening.
      METHODS: New entrants aged 16-34 years predominantly from South Asia (India,
      Pakistan and Bangladesh), with tuberculin tests inappropriately positive for
      their BCG history were identified for the years 1989-2001 inclusive from a new
      entrant database. These entrants were compared with the current GP registration
      database to see if local residence could be confirmed and the local TB
      notification database to October 2008. Survival analysis was carried out using
      Kaplan-Meier survival curves and a Cox Regression model. RESULTS: Four hundred
      and seventy-nine such new entrants with normal initial chest X-rays were
      identified. Of these 402 (84%) registered with a General Practitioner in East
      Lancashire for a period of time and could be followed up by this study. The crude
      incidence density of active TB amongst these individuals with latent disease was
      1297 per 100 000 person-years (95% CI; 991-1698 per 100 000 person-years). After
      10 and 15 years of follow-up 13.5 and 16.3% of individuals, respectively, had
      progressed on to active disease. CONCLUSION: This patient-derived, rather than
      estimated, data shows a minimum risk of TB disease of 16.3% at 15 years. The 2006
      NICE economic appraisal, suggested that treatment for latent TB infection (LTBI)
      was cost-effective when the incidence of clinical TB over 15 years surpassed 18%
      in these populations. The 2011 NICE economic appraisal reduced this to 12% active
      TB over 15 years, and showed that at 16% active TB over 15 years a single
      interferon gamma release assay was the most cost-effective strategy. Further
      cohort studies are urgently needed to confirm or revise the assumptions behind
      the 2011 NICE economic appraisal.

PMID- 24277781
TI  - The intriguing issue of genetic predisposition and the importance of
      identification of pre-clinical markers of endothelial damage in radiotherapy
      induced cardiotoxicity.

PMID- 24277782
TI  - The current state of myocardial contrast echocardiography: what can we read
      between the lines?

PMID- 24277783
TI  - How many have died from undiagnosed human immunodeficiency virus-associated
      histoplasmosis, a treatable disease? Time to act.
AB  - Human immunodeficiency virus (HIV)-associated disseminated Histoplasma capsulatum
      capsulatum infection often mimics tuberculosis. This disease is well know in the
      United States but is dramatically underdiagnosed in Central and South America. In
      the Amazon region, given the available incidence data and the regional HIV
      prevalence, it is expected that, every year, 1,500 cases of histoplasmosis affect
      HIV patients in that region alone. Given the mortality in undiagnosed patients,
      at least 600 patients would be expected to die from an undiagnosed but treatable
      disease. The lack of a simple diagnostic tool and the lack of awareness by
      clinicians spiral in a vicious cycle and made a major problem invisible for 30
      years. The HIV/acquired immunodeficiency syndrome community should tackle this
      problem now to prevent numerous avoidable deaths from HIV-associated
      histoplasmosis in the region and elsewhere.

PMID- 24277785
TI  - The peculiar epidemiology of dracunculiasis in Chad.
AB  - Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10
      years. In April 2012 active village-based surveillance was initiated to determine
      where, when, and how transmission of the disease was occurring, and to implement
      interventions to interrupt it. The current epidemiologic pattern of the disease
      in Chad is unlike that seen previously in Chad or other endemic countries, i.e.,
      no clustering of cases by village or association with a common water source, the
      average number of worms per person was small, and a large number of dogs were
      found to be infected. Molecular sequencing suggests these infections were all
      caused by Dracunculus medinensis. It appears that the infection in dogs is
      serving as the major driving force sustaining transmission in Chad, that an
      aberrant life cycle involving a paratenic host common to people and dogs is
      occurring, and that the cases in humans are sporadic and incidental.

PMID- 24277784
TI  - Pre-existing cross-reactive antibodies to avian influenza H5N1 and 2009 pandemic
      H1N1 in US military personnel.
AB  - We studied cross-reactive antibodies against avian influenza H5N1 and 2009
      pandemic (p) H1N1 in 200 serum samples from US military personnel collected
      before the H1N1 pandemic. Assays used to measure antibodies against viral
      proteins involved in protection included a hemagglutination inhibition (HI) assay
      and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies
      against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5)
      pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some
      US military personnel had cross-neutralizing antibodies against H5N1 (14%) and
      2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009
      pH1N1 were 4.4 times higher in subjects receiving more than five inactivated
      whole influenza virus vaccinations than those subjects with no record of
      vaccination. Although unclear if the result of prior vaccination or disease
      exposure, these pre-existing antibodies may prevent or reduce disease severity.

PMID- 24277786
TI  - Needs for monitoring mosquito transmission of malaria in a pre-elimination world.
AB  - As global efforts to eliminate malaria intensify, accurate information on vector
      populations and transmission dynamics is critical for directing control efforts,
      developing new control tools, and predicting the effects of these interventions
      under various conditions. Currently available sampling tools for mosquito
      population monitoring suffer from well-recognized limitations. As reported in
      this workshop summary, a recent gathering of medical entomologists, modelers, and
      malaria experts reviewed these issues and agreed that efforts are needed to
      improve methods to monitor key transmission parameters. Identified needs include
      standardized methods for sampling of both mosquito adults and larvae, improved
      tools for mosquito species identification and age-grading, and a better means for
      determining the entomological inoculation rate.

PMID- 24277787
TI  - Conservation efforts and malaria in the Brazilian Amazon.
AB  - We respond to Valle and Clark, who assert that "conservation efforts may increase
      malaria burden in the Brazilian Amazon," because the relationship between forest
      cover and malaria incidence was stronger than the effect of the deforestation
      rate. We contend that their conclusion is flawed because of limitations in their
      methodology that we discuss in detail. Most important are the exclusion of one
      half the original data without a discussion of selection bias, the lack of model
      adjustment for either population growth or migration, and the crude
      classifications of land cover and protected areas that lead to aggregation bias.
      Of greater significance, we stress the need for caution in the interpretation of
      data that could have profound effects on regional land use decisions.

PMID- 24277788
TI  - Recurrences of visceral leishmaniasis caused by Leishmania siamensis after
      treatment with amphotericin B in a seronegative child.
AB  - We report the first case of visceral leishmaniasis caused by Leishmania siamensis
      in a seronegative child. She was treated with amphotericin B at 1 mg/kg/day for 3
      weeks; however, recurrences occurred twice. The patient was cured after the
      administration of amphotericin B for 5 weeks and monthly prophylaxis for 6
      months.

PMID- 24277789
TI  - Healthcare access and health beliefs of the indigenous peoples in remote
      Amazonian Peru.
AB  - Little is published about the health issues of traditional communities in the
      remote Peruvian Amazon. This study assessed healthcare access, health
      perceptions, and beliefs of the indigenous population along the Ampiyacu and
      Yaguasyacu rivers in north-eastern Peru. One hundred and seventy-nine adult
      inhabitants of 10 remote settlements attending health clinics were interviewed
      during a medical services trip in April 2012. Demographics, health status, access
      to healthcare, health education, sanitation, alcohol use, and smoke exposure were
      recorded. Our findings indicate that poverty, household overcrowding, and poor
      sanitation remain commonplace in this group. Furthermore, there are poor levels
      of health education and on-going barriers to accessing healthcare. Healthcare
      access and health education remain poor in the remote Peruvian Amazon. This
      combined with poverty and its sequelae render this population vulnerable to
      disease.

PMID- 24277790
TI  - Impact of sputum quality and quantity on smear and culture positivity: findings
      from a tuberculosis prevalence study in central India.
AB  - BACKGROUND: The objective of this study was to assess the impact of sputum
      quality and quantity on smear and culture positivity for Mycobacterium
      tuberculosis. METHODS: A total of 14 708 sputum specimens, collected from
      respiratory symptomatics in a TB prevalence survey, were evaluated for gross
      appearance and volume of sputum and examined by smear microscopy and culture.
      RESULTS: The smear and culture positivity increased with the quantity and the up
      gradation in quality of sputum, and the difference was significant. CONCLUSION:
      The study highlights the importance of visual screening of sputum specimens in
      the detection of pulmonary TB particularly in resource limited settings.

PMID- 24277803
TI  - Conformer-specific characterization of nonnative protein states using hydrogen
      exchange and top-down mass spectrometry.
AB  - Characterization of structure and dynamics of nonnative protein states is
      important for understanding molecular mechanisms of processes as diverse as
      folding, binding, aggregation, and enzyme catalysis to name just a few; however,
      selectively probing local minima within rugged energy landscapes remains a
      problem. Mass spectrometry (MS) coupled with hydrogen/deuterium exchange (HDX)
      offers a unique advantage of being able to make a distinction among multiple
      protein conformers that coexist in solution; however, detailed structural
      interrogation of such states previously remained out of reach of HDX MS. In this
      work, we exploited the aforementioned unique feature of HDX MS in combination
      with the ability of MS to isolate narrow populations of protein ions to
      characterize individual protein conformers coexisting in solution in equilibrium.
      Subsequent fragmentation of the protein ions using electron-capture dissociation
      allowed us to allocate the deuterium distribution along the protein backbone,
      yielding a backbone-amide protection map for the selected conformer unaffected by
      contributions from other protein states present in solution. The method was
      tested with the small regulatory protein ubiquitin (Ub), which is known to form
      nonnative intermediate states under a variety of mildly denaturing conditions.
      Protection maps of these intermediate states obtained at residue-level resolution
      provide clear evidence that they are very similar to the so-called A-state of Ub
      that is formed in solutions with low pH and high alcohol. Method validation was
      carried out by comparing the backbone-amide protection map of native Ub with
      those deduced from high-resolution NMR measurements. 

PMID- 24277804
TI  - Anthropogenic emissions of methane in the United States.
AB  - This study quantitatively estimates the spatial distribution of anthropogenic
      methane sources in the United States by combining comprehensive atmospheric
      methane observations, extensive spatial datasets, and a high-resolution
      atmospheric transport model. Results show that current inventories from the US
      Environmental Protection Agency (EPA) and the Emissions Database for Global
      Atmospheric Research underestimate methane emissions nationally by a factor of
      ~1.5 and ~1.7, respectively. Our study indicates that emissions due to ruminants
      and manure are up to twice the magnitude of existing inventories. In addition,
      the discrepancy in methane source estimates is particularly pronounced in the
      south-central United States, where we find total emissions are ~2.7 times greater
      than in most inventories and account for 24 +/- 3% of national emissions. The
      spatial patterns of our emission fluxes and observed methane-propane correlations
      indicate that fossil fuel extraction and refining are major contributors (45 +/-
      13%) in the south-central United States. This result suggests that regional
      methane emissions due to fossil fuel extraction and processing could be 4.9 +/-
      2.6 times larger than in EDGAR, the most comprehensive global methane inventory.
      These results cast doubt on the US EPA's recent decision to downscale its
      estimate of national natural gas emissions by 25-30%. Overall, we conclude that
      methane emissions associated with both the animal husbandry and fossil fuel
      industries have larger greenhouse gas impacts than indicated by existing
      inventories. 

PMID- 24277805
TI  - Remote life-detection criteria, habitable zone boundaries, and the frequency of
      Earth-like planets around M and late K stars.
AB  - The habitable zone (HZ) around a star is typically defined as the region where a
      rocky planet can maintain liquid water on its surface. That definition is
      appropriate, because this allows for the possibility that carbon-based,
      photosynthetic life exists on the planet in sufficient abundance to modify the
      planet's atmosphere in a way that might be remotely detected. Exactly what
      conditions are needed, however, to maintain liquid water remains a topic for
      debate. In the past, modelers have restricted themselves to water-rich planets
      with CO2 and H2O as the only important greenhouse gases. More recently, some
      researchers have suggested broadening the definition to include arid, "Dune"
      planets on the inner edge and planets with captured H2 atmospheres on the outer
      edge, thereby greatly increasing the HZ width. Such planets could exist, but we
      demonstrate that an inner edge limit of 0.59 AU or less is physically
      unrealistic. We further argue that conservative HZ definitions should be used for
      designing future space-based telescopes, but that optimistic definitions may be
      useful in interpreting the data from such missions. In terms of effective solar
      flux, S(eff), the recently recalculated HZ boundaries are: recent Venus--1.78;
      runaway greenhouse--1.04; moist greenhouse--1.01; maximum greenhouse--0.35; and
      early Mars--0.32. Based on a combination of different HZ definitions, the
      frequency of potentially Earth-like planets around late K and M stars observed by
      Kepler is in the range of 0.4-0.5.

PMID- 24277806
TI  - Solar water splitting in a molecular photoelectrochemical cell.
AB  - Artificial photosynthesis and the production of solar fuels could be a key
      element in a future renewable energy economy providing a solution to the energy
      storage problem in solar energy conversion. We describe a hybrid strategy for
      solar water splitting based on a dye sensitized photoelectrosynthesis cell. It
      uses a derivatized, core-shell nanostructured photoanode with the core a high
      surface area conductive metal oxide film--indium tin oxide or antimony tin oxide-
      coated with a thin outer shell of TiO2 formed by atomic layer deposition. A
      "chromophore-catalyst assembly" 1, [(PO3H2)2bpy)2Ru(4-Mebpy-4
      bimpy)Rub(tpy)(OH2)](4+), which combines both light absorber and water oxidation
      catalyst in a single molecule, was attached to the TiO2 shell. Visible photolysis
      of the resulting core-shell assembly structure with a Pt cathode resulted in
      water splitting into hydrogen and oxygen with an absorbed photon conversion
      efficiency of 4.4% at peak photocurrent. 

PMID- 24277807
TI  - Anomalous perovskite PbRuO3 stabilized under high pressure.
AB  - Perovskite oxides ABO3 are important materials used as components in electronic
      devices. The highly compact crystal structure consists of a framework of corner
      shared BO6 octahedra enclosing the A-site cations. Because of these structural
      features, forming a strong bond between A and B cations is highly unlikely and
      has not been reported in the literature. Here we report a pressure-induced first
      order transition in PbRuO3 from a common orthorhombic phase (Pbnm) to an
      orthorhombic phase (Pbn21) at 32 GPa by using synchrotron X-ray diffraction. This
      transition has been further verified with resistivity measurements and Raman
      spectra under high pressure. In contrast to most well-studied perovskites under
      high pressure, the Pbn21 phase of PbRuO3 stabilized at high pressure is a polar
      perovskite. More interestingly, the Pbn21 phase has the most distorted octahedra
      and a shortest Pb-Ru bond length relative to the average Pb-Ru bond length that
      has ever been reported in a perovskite structure. We have also simulated the
      behavior of the PbRuO3 perovskite under high pressure by first principles
      calculations. The calculated critical pressure for the phase transition and
      evolution of lattice parameters under pressure match the experimental results
      quantitatively. Our calculations also reveal that the hybridization between a
      Ru:t2g orbital and an sp hybrid on Pb increases dramatically in the Pbnm phase
      under pressure. This pressure-induced change destabilizes the Pbnm phase to give
      a phase transition to the Pbn21 phase where electrons in the overlapping orbitals
      form bonding and antibonding states along the shortest Ru-Pb direction at P > Pc.

PMID- 24277808
TI  - Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant
      symbiosis.
AB  - The mutualistic symbiosis involving Glomeromycota, a distinctive phylum of early
      diverging Fungi, is widely hypothesized to have promoted the evolution of land
      plants during the middle Paleozoic. These arbuscular mycorrhizal fungi (AMF)
      perform vital functions in the phosphorus cycle that are fundamental to
      sustainable crop plant productivity. The unusual biological features of AMF have
      long fascinated evolutionary biologists. The coenocytic hyphae host a community
      of hundreds of nuclei and reproduce clonally through large multinucleated spores.
      It has been suggested that the AMF maintain a stable assemblage of several
      different genomes during the life cycle, but this genomic organization has been
      questioned. Here we introduce the 153-Mb haploid genome of Rhizophagus
      irregularis and its repertoire of 28,232 genes. The observed low level of genome
      polymorphism (0.43 SNP per kb) is not consistent with the occurrence of multiple,
      highly diverged genomes. The expansion of mating-related genes suggests the
      existence of cryptic sex-related processes. A comparison of gene categories
      confirms that R. irregularis is close to the Mucoromycotina. The AMF obligate
      biotrophy is not explained by genome erosion or any related loss of metabolic
      complexity in central metabolism, but is marked by a lack of genes encoding plant
      cell wall-degrading enzymes and of genes involved in toxin and thiamine
      synthesis. A battery of mycorrhiza-induced secreted proteins is expressed in
      symbiotic tissues. The present comprehensive repertoire of R. irregularis genes
      provides a basis for future research on symbiosis-related mechanisms in
      Glomeromycota. 

PMID- 24277809
TI  - Extinction during reconsolidation of threat memory diminishes prefrontal cortex
      involvement.
AB  - Controlling learned defensive responses through extinction does not alter the
      threat memory itself, but rather regulates its expression via inhibitory
      influence of the prefrontal cortex (PFC) over amygdala. Individual differences in
      amygdala-PFC circuitry function have been linked to trait anxiety and
      posttraumatic stress disorder. This finding suggests that exposure-based
      techniques may actually be least effective in those who suffer from anxiety
      disorders. A theoretical advantage of techniques influencing reconsolidation of
      threat memories is that the threat representation is altered, potentially
      diminishing reliance on this PFC circuitry, resulting in a more persistent
      reduction of defensive reactions. We hypothesized that timing extinction to
      coincide with threat memory reconsolidation would prevent the return of defensive
      reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired
      with shock and the third was not. A day later, one stimulus (reminded CS+) but
      not the other (nonreminded CS+) was presented 10 min before extinction to
      reactivate the threat memory, followed by extinction training for all CSs. The
      recovery of the threat memory was tested 24 h later. Extinction of the
      nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown,
      but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did
      not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results
      suggest that extinction during reconsolidation prevents the return of defensive
      reactions and diminishes PFC involvement. Reducing the necessity of the PFC
      amygdala circuitry to control defensive reactions may help overcome a primary
      obstacle in the long-term efficacy of current treatments for anxiety disorders. 

PMID- 24277810
TI  - Self-organization of axial polarity, inside-out layer pattern, and species
      specific progenitor dynamics in human ES cell-derived neocortex.
AB  - Here, using further optimized 3D culture that allows highly selective induction
      and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we
      demonstrate unique aspects of self-organization in human neocorticogenesis. Self
      organized cortical tissue spontaneously forms a polarity along the dorsocaudal
      ventrorostral axis and undergoes region-specific rolling morphogenesis that
      generates a semispherical structure. The neuroepithelium self-forms a
      multilayered structure including three neuronal zones (subplate, cortical plate,
      and Cajal-Retzius cell zones) and three progenitor zones (ventricular,
      subventricular, and intermediate zones) in the same apical-basal order as seen in
      the human fetal cortex in the early second trimester. In the cortical plate, late
      born neurons tend to localize more basally to early-born neurons, consistent with
      the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone
      contains basal progenitors that share characteristics with outer radial glia
      abundantly found in the human, but not mouse, fetal brain. Thus, human
      neocorticogenesis involves intrinsic programs that enable the emergence of
      complex neocortical features. 

PMID- 24277811
TI  - The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral
      therapy is stable with few genetic changes over time.
AB  - The source and dynamics of persistent HIV-1 during long-term combinational
      antiretroviral therapy (cART) are critical to understanding the barriers to
      curing HIV-1 infection. To address this issue, we isolated and genetically
      characterized HIV-1 DNA from naive and memory T cells from peripheral blood and
      gut-associated lymphoid tissue (GALT) from eight patients after 4-12 y of
      suppressive cART. Our detailed analysis of these eight patients indicates that
      persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4(+)
      T cells [CD45RO(+)/CD27((+/-))]. The HIV-1 infection frequency of CD4(+) T cells
      from peripheral blood and GALT was higher in patients who initiated treatment
      during chronic compared with acute/early infection, indicating that early
      initiation of therapy results in lower HIV-1 reservoir size in blood and gut.
      Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences
      isolated before initiation of cART and intracellular HIV-1 sequences from the T
      cell subsets after 4-12 y of suppressive cART in four of the eight patients.
      However, evolutionary rate analyses estimated no greater than three nucleotide
      substitutions per gene region analyzed during all of the 4-12 y of suppressive
      therapy. We also identified a clearly replication-incompetent viral sequence in
      multiple memory T cells in one patient, strongly supporting asynchronous cell
      replication of a cell containing integrated HIV-1 DNA as the source. This study
      indicates that persistence of a remarkably stable population of infected memory
      cells will be the primary barrier to a cure, and, with little evidence of viral
      replication, this population could be maintained by homeostatic cell
      proliferation or other processes. 

PMID- 24277813
TI  - Retraction for Schuerwegh et al., Evidence for a functional role of IgE
      anticitrullinated protein antibodies in rheumatoid arthritis.

PMID- 24277812
TI  - ORAI1 calcium channel orchestrates skin homeostasis.
AB  - To achieve and maintain skin architecture and homeostasis, keratinocytes must
      intricately balance growth, differentiation, and polarized motility known to be
      governed by calcium. Orai1 is a pore subunit of a store-operated Ca(2+) channel
      that is a major molecular counterpart for Ca(2+) influx in nonexcitable cells. To
      elucidate the physiological significance of Orai1 in skin, we studied its
      functions in epidermis of mice, with targeted disruption of the orai1 gene, human
      skin sections, and primary keratinocytes. We demonstrate that Orai1 protein is
      mainly confined to the basal layer of epidermis where it plays a critical role to
      control keratinocyte proliferation and polarized motility. Orai1 loss of function
      alters keratinocyte differentiation both in vitro and in vivo. Exploring
      underlying mechanisms, we show that the activation of Orai1-mediated calcium
      entry leads to enhancing focal adhesion turnover via a PKCbeta-Calpain-focal
      adhesion kinase pathway. Our findings provide insight into the functions of the
      Orai1 channel in the maintenance of skin homeostasis. 

PMID- 24277814
TI  - Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two
      centrosomal scaffolds, Cep192 and Cep152.
AB  - Centrosomes play an important role in various cellular processes, including
      spindle formation and chromosome segregation. They are composed of two
      orthogonally arranged centrioles, whose duplication occurs only once per cell
      cycle. Accurate control of centriole numbers is essential for the maintenance of
      genomic integrity. Although it is well appreciated that polo-like kinase 4 (Plk4)
      plays a central role in centriole biogenesis, how it is recruited to centrosomes
      and whether this step is necessary for centriole biogenesis remain largely
      elusive. Here we showed that Plk4 localizes to distinct subcentrosomal regions in
      a temporally and spatially regulated manner, and that Cep192 and Cep152 serve as
      two distinct scaffolds that recruit Plk4 to centrosomes in a hierarchical order.
      Interestingly, Cep192 and Cep152 competitively interacted with the cryptic polo
      box of Plk4 through their homologous N-terminal sequences containing acidic-alpha
      helix and N/Q-rich motifs. Consistent with these observations, the expression of
      either one of these N-terminal fragments was sufficient to delocalize Plk4 from
      centrosomes. Furthermore, loss of the Cep192- or Cep152-dependent interaction
      with Plk4 resulted in impaired centriole duplication that led to delayed cell
      proliferation. Thus, the spatiotemporal regulation of Plk4 localization by two
      hierarchical scaffolds, Cep192 and Cep152, is critical for centriole biogenesis. 

PMID- 24277816
TI  - Synthesis and delivery of short, noncoding RNA by B lymphocytes.
AB  - Evolutionarily conserved short (20-30 nucleotides) noncoding RNAs (microRNAs) are
      powerful regulators of gene expression in a variety of physiological and
      pathological processes. As such, means to efficiently modulate microRNA function
      constitute an important therapeutic opportunity. Here we demonstrate that primary
      B lymphocytes can be genetically programmed with nonviral plasmid DNA for the
      biogenesis and delivery of antisense sequences (anti-microRNA) against microRNA
      150 (miR-150). Within 18 h of transfection with an anti-miR-150 construct,
      primary B lymphocytes secrete ~3,000 copies of anti-miR-150 molecules per cell.
      Anti-miR-150 molecules released by B lymphocytes were internalized by CD8 T
      lymphocytes during cross-priming in vitro and in vivo, resulting in marked down
      regulation of endogenous miR-150. However, such internalization was not observed
      in the absence of cross-priming. These results suggest that shuttling anti-miR
      150 molecules from B lymphocytes to T cells requires the activation of receiver T
      cells via the antigen receptor. Finally, anti-miR-150 synthesized in B cells were
      secreted both as free and extracellular vesicle-associated fractions, but only
      extracellular vesicle-associated anti-miR-150 were apparently taken up by CD8 T
      cells. Collectively, these data indicate that primary B lymphocytes represent an
      efficient platform for the synthesis and delivery of short, noncoding RNA, paving
      the way for an approach to immunogenomic therapies. 

PMID- 24277815
TI  - Cognition, mood, and physiological concentrations of sex hormones in the early
      and late postmenopause.
AB  - Variations in the hormonal milieu after menopause may influence neural processes
      concerned with cognition, cognitive aging, and mood, but findings are
      inconsistent. In particular, cognitive effects of estradiol may vary with time
      since menopause, but this prediction has not been assessed directly using serum
      hormone concentrations. We studied 643 healthy postmenopausal women not using
      hormone therapy who were recruited into early (<6 y after menopause) and late
      (10+ y after menopause) groups. Women were administered a comprehensive
      neuropsychological battery and assessed with the Center for Epidemiologic Studies
      Depression Scale. They provided serum for free estradiol, estrone, progesterone,
      free testosterone, and sex hormone binding globulin measurements. Cognitive
      outcomes were standardized composite measures of verbal episodic memory,
      executive functions, and global cognition. Covariate-adjusted linear regression
      analyses were conducted for each hormone separately and after adjustment for
      other hormone levels. Endogenous sex steroid levels were unassociated with
      cognitive composites, but sex hormone binding globulin was positively associated
      with verbal memory. Results for early and late groups did not differ
      significantly, although progesterone concentrations were significantly positively
      associated with verbal memory and global cognition in early group women. Hormone
      concentrations were not significantly related to mood. Results fail to support
      the hypothesis that temporal proximity to menopause modifies the relation between
      endogenous serum levels of estradiol and verbal memory, executive functions, or
      global cognition. Physiological variations in endogenous postmenopausal levels of
      sex steroid hormones are not substantially related to these aspects of cognition
      or mood; positive associations for progesterone and sex hormone binding globulin
      merit additional study. 

PMID- 24277817
TI  - Death-specific protein in a marine diatom regulates photosynthetic responses to
      iron and light availability.
AB  - Diatoms, unicellular phytoplankton that account for ~40% of marine primary
      productivity, often dominate coastal and open-ocean upwelling zones. Limitation
      of growth and productivity by iron at low light is attributed to an elevated
      cellular Fe requirement for the synthesis of Fe-rich photosynthetic proteins. In
      the dynamic coastal environment, Fe concentrations and daily surface irradiance
      levels can vary by two to three orders of magnitude on short spatial and temporal
      scales. Although genome-wide studies are beginning to provide insight into the
      molecular mechanisms used by diatoms to rapidly respond to such fluxes, their
      functional role in mediating the Fe stress response remains uncharacterized.
      Here, we show, using reverse genetics, that a death-specific protein (DSP;
      previously named for its apparent association with cell death) in the coastal
      diatom Thalassiosira pseudonana (TpDSP1) localizes to the plastid and enhances
      growth during acute Fe limitation at subsaturating light by increasing the
      photosynthetic efficiency of carbon fixation. Clone lines overexpressing TpDSP1
      had a lower quantum requirement for growth, increased levels of photosynthetic
      and carbon fixation proteins, and increased cyclic electron flow around
      photosystem I. Cyclic electron flow is an ATP-producing pathway essential in
      higher plants and chlorophytes with a heretofore unappreciated role in diatoms.
      However, cells under replete conditions were characterized as having markedly
      reduced growth and photosynthetic rates at saturating light, thereby constraining
      the benefits afforded by overexpression. Widespread distribution of DSP-like
      sequences in environmental metagenomic and metatranscriptomic datasets highlights
      the presence and relevance of this protein in natural phytoplankton populations
      in diverse oceanic regimes. 

PMID- 24277818
TI  - Unsteady penetration of a target by a liquid jet.
AB  - It is widely acknowledged that ceramic armor experiences an unsteady penetration
      response: an impacting projectile may erode on the surface of a ceramic target
      without substantial penetration for a significant amount of time and then
      suddenly start to penetrate the target. Although known for more than four
      decades, this phenomenon, commonly referred to as dwell, remains largely
      unexplained. Here, we use scaled analog experiments with a low-speed water jet
      and a soft, translucent target material to investigate dwell. The transient
      target response, in terms of depth of penetration and impact force, is captured
      using a high-speed camera in combination with a piezoelectric force sensor. We
      observe the phenomenon of dwell using a soft (noncracking) target material. The
      results show that the penetration rate increases when the flow of the impacting
      water jet is reversed due to the deformation of the jet-target interface--this
      reversal is also associated with an increase in the force exerted by the jet on
      the target. Creep penetration experiments with a constant indentation force did
      not show an increase in the penetration rate, confirming that flow reversal is
      the cause of the unsteady penetration rate. Our results suggest that dwell can
      occur in a ductile noncracking target due to flow reversal. This phenomenon of
      flow reversal is rather widespread and present in a wide range of impact
      situations, including water-jet cutting, needleless injection, and deposit
      removal via a fluid jet. 

PMID- 24277819
TI  - Orexin/hypocretin system modulates amygdala-dependent threat learning through the
      locus coeruleus.
AB  - Survival in a dangerous environment requires learning about stimuli that predict
      harm. Although recent work has focused on the amygdala as the locus of aversive
      memory formation, the hypothalamus has long been implicated in emotional
      regulation, and the hypothalamic neuropeptide orexin (hypocretin) is involved in
      anxiety states and arousal. Nevertheless, little is known about the role of
      orexin in aversive memory formation. Using a combination of behavioral
      pharmacology, slice physiology, and optogenetic techniques, we show that orexin
      acts upstream of the amygdala via the noradrenergic locus coeruleus to enable
      threat (fear) learning, specifically during the aversive event. Our results are
      consistent with clinical studies linking orexin levels to aversive learning and
      anxiety in humans and dysregulation of the orexin system may contribute to the
      etiology of fear and anxiety disorders. 

PMID- 24277820
TI  - ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by
      inducing cellular nucleotide release.
AB  - Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by
      progressive ectopic mineralization of the skin, eyes, and arteries, for which no
      effective treatment exists. PXE is caused by inactivating mutations in the gene
      encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent
      efflux transporter present mainly in the liver. Abcc6(-/-) mice have been
      instrumental in demonstrating that PXE is a metabolic disease caused by the
      absence of an unknown factor in the circulation, the presence of which depends on
      ABCC6 in the liver. Why absence of this factor results in PXE has remained a
      mystery. Here we report that medium from HEK293 cells overexpressing either human
      or rat ABCC6 potently inhibits mineralization in vitro, whereas medium from
      HEK293 control cells does not. Untargeted metabolomics revealed that cells
      expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though
      ABCC6 itself does not transport nucleoside triphosphates. Extracellularly,
      ectonucleotidases hydrolyze the excreted nucleoside triphosphates to nucleoside
      monophosphates and inorganic pyrophosphate (PPi), a strong inhibitor of
      mineralization that plays a pivotal role in several mineralization disorders
      similar to PXE. The in vivo relevance of our data are demonstrated in Abcc6(-/-)
      mice, which had plasma PPi levels <40% of those found in WT mice. This study
      provides insight into how ABCC6 affects PXE. Our data indicate that the factor
      that normally prevents PXE is PPi, which is provided to the circulation in the
      form of nucleoside triphosphates via an as-yet unidentified but ABCC6-dependent
      mechanism. 

PMID- 24277821
TI  - Unintended imitation affects success in a competitive game.
AB  - Imitation typically occurs in social contexts where people interact and have
      common goals. Here, we show that people are also highly susceptible to imitate
      each other in a competitive context. Pairs of players performed a competitive and
      fast-reaching task (a variant of the arcade whac-a-mole game) in which money
      could be earned if players hit brief-appearing visual targets on a large
      touchscreen before their opponents. In three separate experiments, we demonstrate
      that reaction times and movements were highly correlated within pairs of players.
      Players affected their success by imitating each other, and imitation depended on
      the visibility of the opponent's behavior. Imitation persisted, despite the
      competitive and demanding nature of the game, even if this resulted in lower
      scores and payoffs and even when there was no need to counteract the opponent's
      actions. 

PMID- 24277822
TI  - Microbial biogeography of wine grapes is conditioned by cultivar, vintage, and
      climate.
AB  - Wine grapes present a unique biogeography model, wherein microbial biodiversity
      patterns across viticultural zones not only answer questions of dispersal and
      community maintenance, they are also an inherent component of the quality,
      consumer acceptance, and economic appreciation of a culturally important food
      product. On their journey from the vineyard to the wine bottle, grapes are
      transformed to wine through microbial activity, with indisputable consequences
      for wine quality parameters. Wine grapes harbor a wide range of microbes
      originating from the surrounding environment, many of which are recognized for
      their role in grapevine health and wine quality. However, determinants of
      regional wine characteristics have not been identified, but are frequently
      assumed to stem from viticultural or geological factors alone. This study used a
      high-throughput, short-amplicon sequencing approach to demonstrate that regional,
      site-specific, and grape-variety factors shape the fungal and bacterial consortia
      inhabiting wine-grape surfaces. Furthermore, these microbial assemblages are
      correlated to specific climatic features, suggesting a link between vineyard
      environmental conditions and microbial inhabitation patterns. Taken together,
      these factors shape the unique microbial inputs to regional wine fermentations,
      posing the existence of nonrandom "microbial terroir" as a determining factor in
      regional variation among wine grapes. 

PMID- 24277823
TI  - The transcriptional coactivator PGC-1alpha is dispensable for chronic overload
      induced skeletal muscle hypertrophy and metabolic remodeling.
AB  - Skeletal muscle mass loss and dysfunction have been linked to many diseases.
      Conversely, resistance exercise, mainly by activating mammalian target of
      rapamycin complex 1 (mTORC1), promotes skeletal muscle hypertrophy and exerts
      several therapeutic effects. Moreover, mTORC1, along with peroxisome proliferator
      activated receptor gamma coactivator 1alpha (PGC-1alpha), regulates skeletal
      muscle metabolism. However, it is unclear whether PGC-1alpha is required for
      skeletal muscle adaptations after overload. Here we show that although chronic
      overload of skeletal muscle via synergist ablation (SA) strongly induces
      hypertrophy and a switch toward a slow-contractile phenotype, these effects were
      independent of PGC-1alpha. In fact, SA down-regulated PGC-1alpha expression and
      led to a repression of energy metabolism. Interestingly, however, PGC-1alpha
      deletion preserved peak force after SA. Taken together, our data suggest that PGC
      1alpha is not involved in skeletal muscle remodeling induced by SA. 

PMID- 24277824
TI  - Crossing the divide between homogeneous and heterogeneous catalysis in water
      oxidation.
AB  - Enhancing the surface binding stability of chromophores, catalysts, and
      chromophore-catalyst assemblies attached to metal oxide surfaces is an important
      element in furthering the development of dye sensitized solar cells,
      photoelectrosynthesis cells, and interfacial molecular catalysis. Phosphonate
      derivatized catalysts and molecular assemblies provide a basis for sustained
      water oxidation on these surfaces in acidic solution but are unstable toward
      hydrolysis and loss from surfaces as the pH is increased. Here, we report
      enhanced surface binding stability of a phosphonate-derivatized water oxidation
      catalyst over a wide pH range (1-12) by atomic layer deposition of an overlayer
      of TiO2. Increased stability of surface binding, and the reactivity of the bound
      catalyst, provides a hybrid approach to heterogeneous catalysis combining the
      advantages of systematic modifications possible by chemical synthesis with
      heterogeneous reactivity. For the surface-stabilized catalyst, greatly enhanced
      rates of water oxidation are observed upon addition of buffer bases -H2PO(
      )(4)/HPO(2-)(4), B(OH)3/B(OH)2 O-, HPO(2-)4 /PO(3-)(4) - and with a pathway
      identified in which O-atom transfer to OH(-) occurs with a rate constant increase
      of 10(6) compared to water oxidation in acid.

PMID- 24277825
TI  - T-type channel blockade impairs long-term potentiation at the parallel fiber
      Purkinje cell synapse and cerebellar learning.
AB  - CaV3.1 T-type channels are abundant at the cerebellar synapse between parallel
      fibers and Purkinje cells where they contribute to synaptic depolarization. So
      far, no specific physiological function has been attributed to these channels
      neither as charge carriers nor more specifically as Ca(2+) carriers. Here we
      analyze their incidence on synaptic plasticity, motor behavior, and cerebellar
      motor learning, comparing WT animals and mice where T-type channel function has
      been abolished either by gene deletion or by acute pharmacological blockade. At
      the cellular level, we show that CaV3.1 channels are required for long-term
      potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple
      spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T
      type current blockade results in impaired motor performance in particular when a
      good body balance is required. Because motor behavior integrates reflexes and
      past memories of learned behavior, this suggests impaired learning. Indeed,
      subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals
      impaired cerebellum-dependent motor learning. These data identify a role of low
      voltage activated calcium channels in synaptic plasticity and establish a role
      for CaV3.1 channels in cerebellar learning. 

PMID- 24277826
TI  - Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy
      inducing peptides, starvation, and hypoxia-ischemia.
AB  - A long-standing controversy is whether autophagy is a bona fide cause of
      mammalian cell death. We used a cell-penetrating autophagy-inducing peptide, Tat
      Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether
      high levels of autophagy result in cell death by autophagy. Here we show that Tat
      Beclin 1 induces dose-dependent death that is blocked by pharmacological or
      genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death,
      termed "autosis," has unique morphological features, including increased
      autophagosomes/autolysosomes and nuclear convolution at early stages, and focal
      swelling of the perinuclear space at late stages. We also observed autotic death
      in cells during stress conditions, including in a subpopulation of nutrient
      starved cells in vitro and in hippocampal neurons of neonatal rats subjected to
      cerebral hypoxia-ischemia in vivo. A chemical screen of ~5,000 known bioactive
      compounds revealed that cardiac glycosides, antagonists of Na(+),K(+)-ATPase,
      inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown
      of the Na(+),K(+)-ATPase alpha1 subunit blocks peptide and starvation-induced
      autosis in vitro. Thus, we have identified a unique form of autophagy-dependent
      cell death, a Food and Drug Administration-approved class of compounds that
      inhibit such death, and a crucial role for Na(+),K(+)-ATPase in its regulation.
      These findings have implications for understanding how cells die during certain
      stress conditions and how such cell death might be prevented.

PMID- 24277827
TI  - Memory and synaptic deficits in Hip14/DHHC17 knockout mice.
AB  - Palmitoylation of neurotransmitter receptors and associated scaffold proteins
      regulates their membrane association in a rapid, reversible, and activity
      dependent fashion. This makes palmitoylation an attractive candidate as a key
      regulator of the fast, reversible, and activity-dependent insertion of synaptic
      proteins required during the induction and expression of long-term plasticity.
      Here we describe that the constitutive loss of huntingtin interacting protein 14
      (Hip14, also known as DHHC17), a single member of the broad palmitoyl
      acyltransferase (PAT) family, produces marked alterations in synaptic function in
      varied brain regions and significantly impairs hippocampal memory and synaptic
      plasticity. The data presented suggest that, even though the substrate pool is
      overlapping for the 23 known PAT family members, the function of a single PAT has
      marked effects upon physiology and cognition. Moreover, an improved understanding
      of the role of PATs in synaptic modification and maintenance highlights a
      potential strategy for intervention against early cognitive impairments in
      neurodegenerative disease. 

PMID- 24277829
TI  - Quantitative geometry.

PMID- 24277828
TI  - Acellular pertussis vaccines protect against disease but fail to prevent
      infection and transmission in a nonhuman primate model.
AB  - Pertussis is a highly contagious respiratory illness caused by the bacterial
      pathogen Bordetella pertussis. Pertussis rates in the United States have been
      rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis
      resurgence is not completely understood, we hypothesize that current acellular
      pertussis (aP) vaccines fail to prevent colonization and transmission. To test
      our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP
      or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo.
      Infection was followed by quantifying colonization in nasopharyngeal washes and
      monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected
      from severe pertussis-associated symptoms but not from colonization, did not
      clear the infection faster than naive animals, and readily transmitted B.
      pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid
      clearance compared with naive and aP-vaccinated animals. By comparison,
      previously infected animals were not colonized upon secondary infection. Although
      all vaccinated and previously infected animals had robust serum antibody
      responses, we found key differences in T-cell immunity. Previously infected
      animals and wP-vaccinated animals possess strong B. pertussis-specific T helper
      17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2
      response instead. The observation that aP, which induces an immune response
      mismatched to that induced by natural infection, fails to prevent colonization or
      transmission provides a plausible explanation for the resurgence of pertussis and
      suggests that optimal control of pertussis will require the development of
      improved vaccines. 

PMID- 24277830
TI  - Atmospheric deposition of methanol over the Atlantic Ocean.
AB  - In the troposphere, methanol (CH3OH) is present ubiquitously and second in
      abundance among organic gases after methane. In the surface ocean, methanol
      represents a supply of energy and carbon for marine microbes. Here we report
      direct measurements of air-sea methanol transfer along a ~10,000-km north-south
      transect of the Atlantic. The flux of methanol was consistently from the
      atmosphere to the ocean. Constrained by the aerodynamic limit and measured rate
      of air-sea sensible heat exchange, methanol transfer resembles a one-way
      depositional process, which suggests dissolved methanol concentrations near the
      water surface that are lower than what were measured at ~5 m depth, for reasons
      currently unknown. We estimate the global oceanic uptake of methanol and examine
      the lifetimes of this compound in the lower atmosphere and upper ocean with
      respect to gas exchange. We also constrain the molecular diffusional resistance
      above the ocean surface-an important term for improving air-sea gas exchange
      models. 

PMID- 24277831
TI  - Long-period rhythmic synchronous firing in a scale-free network.
AB  - Stimulus information is encoded in the spatial-temporal structures of external
      inputs to the neural system. The ability to extract the temporal information of
      inputs is fundamental to brain function. It has been found that the neural system
      can memorize temporal intervals of visual inputs in the order of seconds. Here we
      investigate whether the intrinsic dynamics of a large-size neural circuit alone
      can achieve this goal. The network models we consider have scale-free topology
      and the property that hub neurons are difficult to be activated. The latter is
      implemented by either including abundant electrical synapses between neurons or
      considering chemical synapses whose efficacy decreases with the connectivity of
      the postsynaptic neuron. We find that hub neurons trigger synchronous firing
      across the network, loops formed by low-degree neurons determine the rhythm of
      synchronous firing, and the hardness of exciting hub neurons avoids epileptic
      firing of the network. Our model successfully reproduces the experimentally
      observed rhythmic synchronous firing with long periods and supports the notion
      that the neural system can process temporal information through the dynamics of
      local circuits in a distributed way. 

PMID- 24277832
TI  - Broad-scale phylogenomics provides insights into retrovirus-host evolution.
AB  - Genomic data provide an excellent resource to improve understanding of retrovirus
      evolution and the complex relationships among viruses and their hosts. In
      conjunction with broad-scale in silico screening of vertebrate genomes, this
      resource offers an opportunity to complement data on the evolution and frequency
      of past retroviral spread and so evaluate future risks and limitations for
      horizontal transmission between different host species. Here, we develop a
      methodology for extracting phylogenetic signal from large endogenous retrovirus
      (ERV) datasets by collapsing information to facilitate broad-scale phylogenomics
      across a wide sample of hosts. Starting with nearly 90,000 ERVs from 60
      vertebrate host genomes, we construct phylogenetic hypotheses and draw inferences
      regarding the designation, host distribution, origin, and transmission of the
      Gammaretrovirus genus and associated class I ERVs. Our results uncover remarkable
      depths in retroviral sequence diversity, supported within a phylogenetic context.
      This finding suggests that current infectious exogenous retrovirus diversity may
      be underestimated, adding credence to the possibility that many additional
      exogenous retroviruses may remain to be discovered in vertebrate taxa. We
      demonstrate a history of frequent horizontal interorder transmissions from a
      rodent reservoir and suggest that rats may have acted as important overlooked
      facilitators of gammaretrovirus spread across diverse mammalian hosts. Together,
      these results demonstrate the promise of the methodology used here to analyze
      large ERV datasets and improve understanding of retroviral evolution and
      diversity for utilization in wider applications. 

PMID- 24277833
TI  - Profile of Martin Karplus, Michael Levitt, and Arieh Warshel, 2013 nobel
      laureates in chemistry.

PMID- 24277834
TI  - Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes
      with anti-PD-L1 immunotherapy in pancreatic cancer.
AB  - An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the
      analysis of why immunotherapy is ineffective in this human disease. Despite
      finding that PDA-bearing mice had cancer cell-specific CD8(+) T cells, the mice,
      like human patients with PDA, did not respond to two immunological checkpoint
      antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte
      associated protein 4 (alpha-CTLA-4) and alpha-programmed cell death 1 ligand 1
      (alpha-PD-L1). Immune control of PDA growth was achieved, however, by depleting
      carcinoma-associated fibroblasts (CAFs) that express fibroblast activation
      protein (FAP). The depletion of the FAP(+) stromal cell also uncovered the
      antitumor effects of alpha-CTLA-4 and alpha-PD-L1, indicating that its immune
      suppressive activity accounts for the failure of these T-cell checkpoint
      antagonists. Three findings suggested that chemokine (C-X-C motif) ligand 12
      (CXCL12) explained the overriding immunosuppression by the FAP(+) cell: T cells
      were absent from regions of the tumor containing cancer cells, cancer cells were
      coated with the chemokine, CXCL12, and the FAP(+) CAF was the principal source of
      CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor chemokine (C-X-C
      motif) receptor 4 inhibitor, induced rapid T-cell accumulation among cancer cells
      and acted synergistically with alpha-PD-L1 to greatly diminish cancer cells,
      which were identified by their loss of heterozygosity of Trp53 gene. The residual
      tumor was composed only of premalignant epithelial cells and inflammatory cells.
      Thus, a single protein, CXCL12, from a single stromal cell type, the FAP(+) CAF,
      may direct tumor immune evasion in a model of human PDA. 

PMID- 24277835
TI  - Spectral redemption in clustering sparse networks.
AB  - Spectral algorithms are classic approaches to clustering and community detection
      in networks. However, for sparse networks the standard versions of these
      algorithms are suboptimal, in some cases completely failing to detect communities
      even when other algorithms such as belief propagation can do so. Here, we present
      a class of spectral algorithms based on a nonbacktracking walk on the directed
      edges of the graph. The spectrum of this operator is much better-behaved than
      that of the adjacency matrix or other commonly used matrices, maintaining a
      strong separation between the bulk eigenvalues and the eigenvalues relevant to
      community structure even in the sparse case. We show that our algorithm is
      optimal for graphs generated by the stochastic block model, detecting communities
      all of the way down to the theoretical limit. We also show the spectrum of the
      nonbacktracking operator for some real-world networks, illustrating its
      advantages over traditional spectral clustering. 

PMID- 24277836
TI  - Quantification of OH and HO2 radicals during the low-temperature oxidation of
      hydrocarbons by Fluorescence Assay by Gas Expansion technique.
AB  - *OH and *HO2 radicals are known to be the key species in the development of
      ignition. A direct measurement of these radicals under low-temperature oxidation
      conditions (T = 550-1,000 K) has been achieved by coupling a technique named
      fluorescence assay by gas expansion, an experimental technique designed for the
      quantification of these radicals in the free atmosphere, to a jet-stirred
      reactor, an experimental device designed for the study of low-temperature
      combustion chemistry. Calibration allows conversion of relative fluorescence
      signals to absolute mole fractions. Such radical mole fraction profiles will
      serve as a benchmark for testing chemical models developed to improve the
      understanding of combustion processes. 

PMID- 24277837
TI  - Spectrally coded optical nanosectioning (SpecON) with biocompatible metal
      dielectric-coated substrates.
AB  - Fluorescence nanosectioning within a submicron region above an interface is
      desirable for many disciplines in the life sciences. A drawback, however, to most
      current approaches is the a priori need to physically scan a sculptured point
      spread function in the axial dimension, which can be undesirable for optically
      sensitive or highly dynamic samples. Here we demonstrate a fluorescence imaging
      approach that can overcome the need for scanning by exploiting the position
      dependent emission spectrum of fluorophores above a simple biocompatible
      nanostructure. To achieve this we have designed a thin metal-dielectric-coated
      substrate, where the spectral modification to the total measured fluorescence can
      be used to estimate the axial fluorophore distribution within distances of 10-150
      nm above the substrate with an accuracy of up to 5-10 nm. The modeling and
      feasibility of the approach are verified and successfully applied to elucidate
      nanoscale adhesion protein and filopodia dynamics in migrating cells. It is
      likely that the general principle can find broader applications in, for example,
      single-molecule studies, biosensing, and studying fast dynamic processes. 

PMID- 24277838
TI  - Internalizing MHC class II-peptide complexes are ubiquitinated in early endosomes
      and targeted for lysosomal degradation.
AB  - As sentinels of the immune system, dendritic cells (DCs) continuously generate
      and turnover antigenic peptide-MHC class II complexes (pMHC-II). pMHC-II
      generation is a complex process that involves many well-characterized MHC-II
      biosynthetic intermediates; however, the mechanisms leading to MHC-II
      turnover/degradation are poorly understood. We now show that pMHC-II complexes
      undergoing clathrin-independent endocytosis from the DC surface are efficiently
      ubiquitinated by the E3 ubiquitin ligase March-I in early endosomes, whereas
      biosynthetically immature MHC-II-Invariant chain (Ii) complexes are not. The
      inability of MHC-II-Ii to serve as a March-I substrate is a consequence of Ii
      sorting motifs that divert the MHC-II-Ii complex away from March-I(+) early
      endosomes. When these sorting motifs are mutated, or when clathrin-mediated
      endocytosis is inhibited, MHC-II-Ii complexes internalize by using a clathrin
      independent endocytosis pathway and are now ubiquitinated as efficiently as pMHC
      II complexes. These data show that the selective ubiquitination of internalizing
      surface pMHC-II in March-I(+) early endosomes promotes degradation of "old" pMHC
      II and spares forms of MHC-II that have not yet loaded antigenic peptides or have
      not yet reached the DC surface. 

PMID- 24277839
TI  - Glutaredoxin regulates vascular development by reversible glutathionylation of
      sirtuin 1.
AB  - Embryonic development depends on complex and precisely orchestrated signaling
      pathways including specific reduction/oxidation cascades. Oxidoreductases of the
      thioredoxin family are key players conveying redox signals through reversible
      posttranslational modifications of protein thiols. The importance of this protein
      family during embryogenesis has recently been exemplified for glutaredoxin 2, a
      vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for
      embryonic brain development. Here, we discovered an essential function of
      glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse
      studies based on two-photon microscopy revealed that morpholino-based knockdown
      of glutaredoxin 2 in zebrafish, a model organism to study vertebrate
      embryogenesis, resulted in a delayed and disordered blood vessel network. We were
      able to show that formation of a functional vascular system requires glutaredoxin
      2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein
      deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue
      in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2
      specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation
      controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved
      between zebrafish and humans. These results link S-glutathionylation to
      vertebrate development and successful embryonic angiogenesis. 

PMID- 24277840
TI  - In situ structure and dynamics of DNA origami determined through molecular
      dynamics simulations.
AB  - The DNA origami method permits folding of long single-stranded DNA into complex
      3D structures with subnanometer precision. Transmission electron microscopy,
      atomic force microscopy, and recently cryo-EM tomography have been used to
      characterize the properties of such DNA origami objects, however their
      microscopic structures and dynamics have remained unknown. Here, we report the
      results of all-atom molecular dynamics simulations that characterized the
      structural and mechanical properties of DNA origami objects in unprecedented
      microscopic detail. When simulated in an aqueous environment, the structures of
      DNA origami objects depart from their idealized targets as a result of steric,
      electrostatic, and solvent-mediated forces. Whereas the global structural
      features of such relaxed conformations conform to the target designs, local
      deformations are abundant and vary in magnitude along the structures. In contrast
      to their free-solution conformation, the Holliday junctions in the DNA origami
      structures adopt a left-handed antiparallel conformation. We find the DNA origami
      structures undergo considerable temporal fluctuations on both local and global
      scales. Analysis of such structural fluctuations reveals the local mechanical
      properties of the DNA origami objects. The lattice type of the structures
      considerably affects global mechanical properties such as bending rigidity. Our
      study demonstrates the potential of all-atom molecular dynamics simulations to
      play a considerable role in future development of the DNA origami field by
      providing accurate, quantitative assessment of local and global structural and
      mechanical properties of DNA origami objects. 

PMID- 24277841
TI  - Constitutively active UVR8 photoreceptor variant in Arabidopsis.
AB  - Arabidopsis thaliana UV RESISTANCE LOCUS 8 (UVR8) is a UV-B photoreceptor that
      initiates photomorphogenic responses underlying acclimation and UV-B tolerance in
      plants. UVR8 is a homodimer in its ground state, and UV-B exposure results in its
      instantaneous monomerization followed by interaction with CONSTITUTIVELY
      PHOTOMORPHOGENIC 1 (COP1), a major factor in UV-B signaling. UV-B photoreception
      by UVR8 is based on intrinsic tryptophan aromatic amino acid residues, with
      tryptophan-285 as the main chromophore. We generated transgenic plants expressing
      UVR8 with a single amino acid change of tryptophan-285 to alanine. UVR8(W285A)
      appears monomeric and shows UV-B-independent interaction with COP1.
      Phenotypically, the plants expressing UVR8(W285A) exhibit constitutive
      photomorphogenesis associated with constitutive activation of target genes,
      elevated levels of anthocyanins, and enhanced, acclimation-independent UV-B
      tolerance. Moreover, we have identified COP1, REPRESSOR OF UV-B
      PHOTOMORPHOGENESIS 1 and 2 (RUP1 and RUP2), and the SUPPRESSOR OF PHYA-105 (SPA)
      family as proteins copurifying with UVR8(W285A). Whereas COP1, RUP1, and RUP2 are
      known to directly interact with UVR8, we show that SPA1 interacts with UVR8
      indirectly through COP1. We conclude that UVR8(W285A) is a constitutively active
      UVR8 photoreceptor variant in Arabidopsis, as is consistent with the crucial
      importance of monomer formation and COP1 binding for UVR8 activity. 

PMID- 24277842
TI  - Chemical map of Schizosaccharomyces pombe reveals species-specific features in
      nucleosome positioning.
AB  - Using a recently developed chemical approach, we have generated a genome-wide map
      of nucleosomes in vivo in Schizosaccharomyces pombe (S. pombe) at base pair
      resolution. The shorter linker length previously identified in S. pombe is due to
      a preponderance of nucleosomes separated by ~4/5 bp, placing nucleosomes on
      opposite faces of the DNA. The periodic dinucleotide feature thought to position
      nucleosomes is equally strong in exons as in introns, demonstrating that
      nucleosome positioning information can be superimposed on coding information.
      Unlike the case in Saccharomyces cerevisiae, A/T-rich sequences are enriched in
      S. pombe nucleosomes, particularly at +/-20 bp around the dyad. This difference
      in nucleosome binding preference gives rise to a major distinction downstream of
      the transcription start site, where nucleosome phasing is highly predictable by
      A/T frequency in S. pombe but not in S. cerevisiae, suggesting that the genomes
      and DNA binding preferences of nucleosomes have coevolved in different species.
      The poly (dA-dT) tracts affect but do not deplete nucleosomes in S. pombe, and
      they prefer special rotational positions within the nucleosome, with longer
      tracts enriched in the 10- to 30-bp region from the dyad. S. pombe does not have
      a well-defined nucleosome-depleted region immediately upstream of most
      transcription start sites; instead, the -1 nucleosome is positioned with the
      expected spacing relative to the +1 nucleosome, and its occupancy is negatively
      correlated with gene expression. Although there is generally very good agreement
      between nucleosome maps generated by chemical cleavage and micrococcal nuclease
      digestion, the chemical map shows consistently higher nucleosome occupancy on DNA
      with high A/T content. 

PMID- 24277843
TI  - Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2
      channel gating.
AB  - The S4 segment and the S4-S5 linker of voltage-gated potassium (Kv) channels are
      crucial for voltage sensing. Previous studies on the Shaker and Kv1.2 channels
      have shown that phosphatidylinositol-4,5-bisphosphate (PIP2) exerts opposing
      effects on Kv channels, up-regulating the current amplitude, while decreasing the
      voltage sensitivity. Interactions between PIP2 and the S4 segment or the S4-S5
      linker in the closed state have been highlighted to explain the effects of PIP2
      on voltage sensitivity. Here, we show that PIP2 preferentially interacts with the
      S4-S5 linker in the open-state KCNQ2 (Kv7.2) channel, whereas it contacts the S2
      S3 loop in the closed state. These interactions are different from the PIP2
      Shaker and PIP2-Kv1.2 interactions. Consistently, PIP2 exerts different effects
      on KCNQ2 relative to the Shaker and Kv1.2 channels; PIP2 up-regulates both the
      current amplitude and voltage sensitivity of the KCNQ2 channel. Disruption of the
      interaction of PIP2 with the S4-S5 linker by a single mutation decreases the
      voltage sensitivity and current amplitude, whereas disruption of the interaction
      with the S2-S3 loop does not alter voltage sensitivity. These results provide
      insight into the mechanism of PIP2 action on KCNQ channels. In the closed state,
      PIP2 is anchored at the S2-S3 loop; upon channel activation, PIP2 interacts with
      the S4-S5 linker and is involved in channel gating. 

PMID- 24277844
TI  - Profile of Edward M. De Robertis.

PMID- 24277845
TI  - Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux
      proteins.
AB  - Chlorhexidine is widely used as an antiseptic or disinfectant in both hospital
      and community settings. A number of bacterial species display resistance to this
      membrane-active biocide. We examined the transcriptomic response of a
      representative nosocomial human pathogen, Acinetobacter baumannii, to
      chlorhexidine to identify the primary chlorhexidine resistance elements. The most
      highly up-regulated genes encoded components of a major multidrug efflux system,
      AdeAB. The next most highly overexpressed gene under chlorhexidine stress was
      annotated as encoding a hypothetical protein, named here as AceI. Orthologs of
      the aceI gene are conserved within the genomes of a broad range of
      proteobacterial species. Expression of aceI or its orthologs from several other
      gamma- or beta-proteobacterial species in Escherichia coli resulted in
      significant increases in resistance to chlorhexidine. Additionally, disruption of
      the aceI ortholog in Acinetobacter baylyi rendered it more susceptible to
      chlorhexidine. The AceI protein was localized to the membrane after
      overexpression in E. coli. This protein was purified, and binding assays
      demonstrated direct and specific interactions between AceI and chlorhexidine.
      Transport assays using [(14)C]-chlorhexidine determined that AceI was able to
      mediate the energy-dependent efflux of chlorhexidine. An E15Q AceI mutant with a
      mutation in a conserved acidic residue, although unable to mediate chlorhexidine
      resistance and transport, was still able to bind chlorhexidine. Taken together,
      these data are consistent with AceI being an active chlorhexidine efflux protein
      and the founding member of a family of bacterial drug efflux transporters. 

PMID- 24277846
TI  - Uncoating of common cold virus is preceded by RNA switching as determined by X
      ray and cryo-EM analyses of the subviral A-particle.
AB  - During infection, viruses undergo conformational changes that lead to delivery of
      their genome into host cytosol. In human rhinovirus A2, this conversion is
      triggered by exposure to acid pH in the endosome. The first subviral
      intermediate, the A-particle, is expanded and has lost the internal viral protein
      4 (VP4), but retains its RNA genome. The nucleic acid is subsequently released,
      presumably through one of the large pores that open at the icosahedral twofold
      axes, and is transferred along a conduit in the endosomal membrane; the remaining
      empty capsids, termed B-particles, are shuttled to lysosomes for degradation.
      Previous structural analyses revealed important differences between the native
      protein shell and the empty capsid. Nonetheless, little is known of A-particle
      architecture or conformation of the RNA core. Using 3D cryo-electron microscopy
      and X-ray crystallography, we found notable changes in RNA-protein contacts
      during conversion of native virus into the A-particle uncoating intermediate. In
      the native virion, we confirmed interaction of nucleotide(s) with Trp(38) of VP2
      and identified additional contacts with the VP1 N terminus. Study of A-particle
      structure showed that the VP2 contact is maintained, that VP1 interactions are
      lost after exit of the VP1 N-terminal extension, and that the RNA also interacts
      with residues of the VP3 N terminus at the fivefold axis. These associations lead
      to formation of a well-ordered RNA layer beneath the protein shell, suggesting
      that these interactions guide ordered RNA egress. 

PMID- 24277847
TI  - Limitations of inclusive fitness.
AB  - Until recently, inclusive fitness has been widely accepted as a general method to
      explain the evolution of social behavior. Affirming and expanding earlier
      criticism, we demonstrate that inclusive fitness is instead a limited concept,
      which exists only for a small subset of evolutionary processes. Inclusive fitness
      assumes that personal fitness is the sum of additive components caused by
      individual actions. This assumption does not hold for the majority of
      evolutionary processes or scenarios. To sidestep this limitation, inclusive
      fitness theorists have proposed a method using linear regression. On the basis of
      this method, it is claimed that inclusive fitness theory (i) predicts the
      direction of allele frequency changes, (ii) reveals the reasons for these
      changes, (iii) is as general as natural selection, and (iv) provides a universal
      design principle for evolution. In this paper we evaluate these claims, and show
      that all of them are unfounded. If the objective is to analyze whether mutations
      that modify social behavior are favored or opposed by natural selection, then no
      aspect of inclusive fitness theory is needed. 

PMID- 24277848
TI  - Acquisition of an Archaea-like ribonuclease H domain by plant L1 retrotransposons
      supports modular evolution.
AB  - Although a variety of non-LTR retrotransposons of the L1 superfamily have been
      found in plant genomes over recent decades, their diversity, distribution, and
      evolution have yet to be analyzed in depth. Here, we perform comprehensive
      comparative and evolutionary analyses of L1 retrotransposons from 29 genomes of
      land plants covering a wide range of taxa. We identify numerous L1 elements in
      these genomes and detect a striking diversity of their domain composition. We
      show that all known land plant L1 retrotransposons can be grouped into five major
      families based on their phylogenetic relationships and domain composition.
      Moreover, we trace the putative evolution timeline that created the current
      variants and reveal that evolutionary events included losses and acquisitions of
      diverse putative RNA-binding domains and the acquisition of an Archaea-like
      ribonuclease H (RNH) domain. We also show that the latter RNH domain is
      autonomously active in vitro and speculate that retrotransposons may play a role
      in the horizontal transfer of RNH between plants, Archaea, and bacteria. The
      acquisition of an Archaea-like RNH domain by plant L1 retrotransposons negates
      the hypothesis that RNH domains in non-LTR retrotransposons have a single origin
      and provides evidence that acquisition happened at least twice. Together, our
      data indicate that the evolution of the investigated retrotransposons can be
      mainly characterized by repeated events of domain rearrangements and identify
      modular evolution as a major trend in the evolution of plant L1 retrotransposons.

PMID- 24277849
TI  - Forecasting long-term gas production from shale.

PMID- 24277850
TI  - Transcription factor evolution in eukaryotes and the assembly of the regulatory
      toolkit in multicellular lineages.
AB  - Transcription factors (TFs) are the main players in transcriptional regulation in
      eukaryotes. However, it remains unclear what role TFs played in the origin of all
      of the different eukaryotic multicellular lineages. In this paper, we explore how
      the origin of TF repertoires shaped eukaryotic evolution and, in particular,
      their role into the emergence of multicellular lineages. We traced the origin and
      expansion of all known TFs through the eukaryotic tree of life, using the
      broadest possible taxon sampling and an updated phylogenetic background. Our
      results show that the most complex multicellular lineages (i.e., those with
      embryonic development, Metazoa and Embryophyta) have the most complex TF
      repertoires, and that these repertoires were assembled in a stepwise manner. We
      also show that a significant part of the metazoan and embryophyte TF toolkits
      evolved earlier, in their respective unicellular ancestors. To gain insights into
      the role of TFs in the development of both embryophytes and metazoans, we
      analyzed TF expression patterns throughout their ontogeny. The expression
      patterns observed in both groups recapitulate those of the whole transcriptome,
      but reveal some important differences. Our comparative genomics and expression
      data reshape our view on how TFs contributed to eukaryotic evolution and reveal
      the importance of TFs to the origins of multicellularity and embryonic
      development. 

PMID- 24277851
TI  - Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for
      cellular receptor.
AB  - Most structural information about poliovirus interaction with neutralizing
      antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies.
      Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies
      and demonstrated that one of them, MAb A12, could neutralize polioviruses of both
      serotypes 1 and 2. This communication presents data on isolation of an additional
      cross-neutralizing antibody (F12) and identification of a previously unknown
      epitope on the surface of poliovirus virions. Epitope mapping was performed by
      sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions
      with Fab fragments. The results have demonstrated that both cross-neutralizing
      antibodies bind the site located at the bottom of the canyon surrounding the
      fivefold axis of symmetry that was previously shown to interact with cellular
      poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2
      through different specific interactions. It was also shown to interact with type
      3 poliovirus, albeit with about 10-fold lower affinity, insufficient for
      effective neutralization. Antibody interaction with the binding site of the
      cellular receptor may explain its broad reactivity and suggest that further
      screening or antibody engineering could lead to a universal antibody capable of
      neutralizing all three serotypes of poliovirus. 

PMID- 24277852
TI  - Suppression of WC-independent frequency transcription by RCO-1 is essential for
      Neurospora circadian clock.
AB  - Rhythmic activation and repression of clock gene transcription is essential for
      the functions of eukaryotic circadian clocks. In the Neurospora circadian
      oscillator, frequency (frq) transcription requires the WHITE COLLAR (WC) complex.
      Here, we show that the transcriptional corepressor regulation of conidiation-1
      (RCO-1) is essential for clock function by regulating frq transcription. In rco-1
      mutants, both overt and molecular rhythms are abolished, frq mRNA levels are
      constantly high, and WC binding to the frq promoter is dramatically reduced.
      Surprisingly, frq mRNA levels were constantly high in the rco-1 wc double
      mutants, indicating that RCO-1 suppresses WC-independent transcription and
      promotes WC complex binding to the frq promoter. Furthermore, RCO-1 is required
      for maintaining normal chromatin structure at the frq locus. Deletion of H3K36
      methyltransferase su(var)3-9-enhancer-of-zeste-trithorax-2 (SET-2) or the
      chromatin remodeling factor CHD-1 leads to WC-independent frq transcription and
      loss of overt rhythms. Together, our results uncover a previously unexpected
      regulatory mechanism for clock gene transcription. 

PMID- 24277853
TI  - Genome-wide mutagenesis of influenza virus reveals unique plasticity of the
      hemagglutinin and NS1 proteins.
AB  - The molecular basis for the diversity across influenza strains is poorly
      understood. To gain insight into this question, we mutagenized the viral genome
      and sequenced recoverable viruses. Only two small regions in the genome were
      enriched for insertions, the hemagglutinin head and the immune-modulatory
      nonstructural protein 1. These proteins play a major role in host adaptation, and
      thus need to be able to evolve rapidly. We propose a model in which certain
      influenza A virus proteins (or protein domains) exist as highly plastic
      scaffolds, which will readily accept mutations yet retain their functionality.
      This model implies that the ability to rapidly acquire mutations is an inherent
      aspect of influenza HA and nonstructural protein 1 proteins; further, this may
      explain why rapid antigenic drift and a broad host range is observed with
      influenza A virus and not with some other RNA viruses. 

PMID- 24277854
TI  - Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974.
AB  - Wnt signaling is one of the key oncogenic pathways in multiple cancers, and
      targeting this pathway is an attractive therapeutic approach. However,
      therapeutic success has been limited because of the lack of therapeutic agents
      for targets in the Wnt pathway and the lack of a defined patient population that
      would be sensitive to a Wnt inhibitor. We developed a screen for small molecules
      that block Wnt secretion. This effort led to the discovery of LGK974, a potent
      and specific small-molecule Porcupine (PORCN) inhibitor. PORCN is a membrane
      bound O-acyltransferase that is required for and dedicated to palmitoylation of
      Wnt ligands, a necessary step in the processing of Wnt ligand secretion. We show
      that LGK974 potently inhibits Wnt signaling in vitro and in vivo, including
      reduction of the Wnt-dependent LRP6 phosphorylation and the expression of Wnt
      target genes, such as AXIN2. LGK974 is potent and efficacious in multiple tumor
      models at well-tolerated doses in vivo, including murine and rat mechanistic
      breast cancer models driven by MMTV-Wnt1 and a human head and neck squamous cell
      carcinoma model (HN30). We also show that head and neck cancer cell lines with
      loss-of-function mutations in the Notch signaling pathway have a high response
      rate to LGK974. Together, these findings provide both a strategy and tools for
      targeting Wnt-driven cancers through the inhibition of PORCN. 

PMID- 24277855
TI  - Genome-scale metabolic reconstructions of multiple Escherichia coli strains
      highlight strain-specific adaptations to nutritional environments.
AB  - Genome-scale models (GEMs) of metabolism were constructed for 55 fully sequenced
      Escherichia coli and Shigella strains. The GEMs enable a systems approach to
      characterizing the pan and core metabolic capabilities of the E. coli species.
      The majority of pan metabolic content was found to consist of alternate catabolic
      pathways for unique nutrient sources. The GEMs were then used to systematically
      analyze growth capabilities in more than 650 different growth-supporting
      environments. The results show that unique strain-specific metabolic capabilities
      correspond to pathotypes and environmental niches. Twelve of the GEMs were used
      to predict growth on six differentiating nutrients, and the predictions were
      found to agree with 80% of experimental outcomes. Additionally, GEMs were used to
      predict strain-specific auxotrophies. Twelve of the strains modeled were
      predicted to be auxotrophic for vitamins niacin (vitamin B3), thiamin (vitamin
      B1), or folate (vitamin B9). Six of the strains modeled have lost biosynthetic
      pathways for essential amino acids methionine, tryptophan, or leucine. Genome
      scale analysis of multiple strains of a species can thus be used to define the
      metabolic essence of a microbial species and delineate growth differences that
      shed light on the adaptation process to a particular microenvironment. 

PMID- 24277857
TI  - Multi-detector CT angiography in case of concomitant pseudoaneurysm and
      arteriovenous fistula of the lateral superior geniculate artery.

PMID- 24277856
TI  - Oxytocin enhances brain reward system responses in men viewing the face of their
      female partner.
AB  - The biological mechanisms underlying long-term partner bonds in humans are
      unclear. The evolutionarily conserved neuropeptide oxytocin (OXT) is associated
      with the formation of partner bonds in some species via interactions with brain
      dopamine reward systems. However, whether it plays a similar role in humans has
      as yet not been established. Here, we report the results of a discovery and a
      replication study, each involving a double-blind, placebo-controlled, within
      subject, pharmaco-functional MRI experiment with 20 heterosexual pair-bonded male
      volunteers. In both experiments, intranasal OXT treatment (24 IU) made subjects
      perceive their female partner's face as more attractive compared with unfamiliar
      women but had no effect on the attractiveness of other familiar women. This
      enhanced positive partner bias was paralleled by an increased response to partner
      stimuli compared with unfamiliar women in brain reward regions including the
      ventral tegmental area and the nucleus accumbens (NAcc). In the left NAcc, OXT
      even augmented the neural response to the partner compared with a familiar woman,
      indicating that this finding is partner-bond specific rather than due to
      familiarity. Taken together, our results suggest that OXT could contribute to
      romantic bonds in men by enhancing their partner's attractiveness and reward
      value compared with other women. 

PMID- 24277858
TI  - A tonsillomedullary stroke causing supranuclear lingual paresis.

PMID- 24277859
TI  - Cyclobacterium xiamenense sp. nov., isolated from aggregates of Chlorella
      autotrophica, and emended description of the genus Cyclobacterium.
AB  - A novel Gram-stain-negative, horseshoe-shaped, non-motile bacterium, designated
      strain KD51(T), forming colonies coloured pink by carotenoid pigments, was
      isolated from aggregates of the alga Chlorella autotrophica collected from the
      coastal sea off the city of Xiamen, Fujian Province, China. 16S rRNA gene
      sequence comparison showed that strain KD51(T) was a member of the genus
      Cyclobacterium, forming a distinct lineage with Cyclobacterium lianum HY9(T). The
      16S rRNA gene sequence similarity between strain KD51(T) and the type strains of
      species of the genus Cyclobacterium ranged from 92.1 % to 95.2 %. Growth occurred
      at 4-40  degrees C (optimum, 28  degrees C), in the presence of 3-9 % NaCl
      (optimum, 3-5 %) and at pH 6-10 (optimum, pH 7.5). The dominant fatty acids (>20
      %) of strain KD51(T) were iso-C15 : 0 (32.2 %) and summed feature 3 (comprising
      C16 : 1omega7c and/or C16 : 1omega6c; 22.2 %). The DNA G+C content was 41.7 mol%
      and the only respiratory quinone was menaquinone-7. On the basis of phenotypic
      data and phylogenetic inference, strain KD51(T) represents a novel species of the
      genus Cyclobacterium, for which the name Cyclobacterium xiamenense sp. nov. is
      proposed. The type strain is KD51(T) ( = CGMCC 1.12432(T) = KCTC 32253(T)). An
      emended description of the genus Cyclobacterium is also proposed. 

PMID- 24277860
TI  - Bacillus panacisoli sp. nov., isolated from ginseng soil.
AB  - A Gram-staining-positive, motile, facultatively anaerobic, endospore-forming and
      rod-shaped bacterium, designated strain CJ32(T), was isolated from ginseng soil
      at Geumsan in Korea. The isolate grew optimally at 30  degrees C, 2% (w/v) NaCl
      and pH 7.0. Colonies of strain CJ32(T) were beige and circular with an entire
      margin on LB agar plates. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain CJ32(T) was associated with the genus Bacillus and was most
      closely related to Bacillus graminis YC6957(T) (97.3% similarity) and Bacillus
      lentus IAM 12466(T) (97.1%). DNA-DNA hybridization with closely related strains
      was below 31.3%. The major respiratory isoprenoid quinone was MK-7. The
      diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic
      acid. The polar lipid profile of strain CJ32(T) consisted of
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and
      several unidentified lipids, including phospholipids, aminolipids and
      aminophospholipids. The predominant fatty acids of strain CJ32(T) were iso-C15:0
      and anteiso-C15:0. The G+C content of the genomic DNA was 35.1 mol%. Based on
      phenotypic, genotypic and phylogenetic data, strain CJ32(T) should be classified
      within a novel species of the genus Bacillus, for which the name Bacillus
      panacisoli sp. nov. is proposed. The type strain is strain CJ32(T) ( = KACC
      17503(T) = JCM 19226(T)).

PMID- 24277861
TI  - Ferruginibacter yonginensis sp. nov., isolated from a mesotrophic artificial
      lake.
AB  - A Gram-stain-negative, rod-shaped, aerobic and reddish-pigmented strain,
      designated HME8442(T), was isolated from a mesotrophic artificial lake. The
      strain grew optimally at 30  degrees C and pH 7 on R2A agar. The major fatty acid
      was iso-C15 : 0. The polar lipids were phosphatidylethanolamine, one unidentified
      aminolipid and three unidentified polar lipids. The predominant respiratory
      quinone was MK-7. The DNA G+C content was 35.8 mol%. Strain HME8442(T) was
      closely related to Ferruginibacter lapsinanis HU1-HG42(T) (94.4 % 16S rRNA gene
      sequence similarity) and Ferruginibacter alkalilentus HU1-GD23(T) (93.9 %). The
      phylogenetic tree based on 16S rRNA gene sequences showed that strain HME8442(T)
      formed a lineage within the genus Ferruginibacter. On the basis of the evidence
      presented in this study, strain HME8442(T) represents a novel species of the
      genus Ferruginibacter, for which the name Ferruginibacter yonginensis sp. nov. is
      proposed. The type strain is HME8442(T) ( = KACC 17314(T) = CECT 8289(T)). 

PMID- 24277862
TI  - Phreatobacter oligotrophus gen. nov., sp. nov., an alphaproteobacterium isolated
      from ultrapure water of the water purification system of a power plant.
AB  - Strains of a novel alphaproteobacterium were isolated from ultrapure water of a
      Hungarian power plant on a newly developed medium. Phylogenetic analysis of the
      16S rRNA gene sequences of the novel strains showed that these bacteria belong to
      a distinct lineage far from any known taxa. Based on the 16S rRNA gene sequences,
      strains PI_31, PI_25 and PI_21(T) exhibited the highest sequence similarity to
      Bosea minatitlanensis AMX51(T) (93.43 %) and Bosea thiooxidans DSM 9653(T) (93.36
      %); similarity to all other taxa was less than 93.23 %. Fatty acid profiles,
      matrix-assisted laser-desorption/ionization time-of-flight mass spectra of cell
      extracts as well as physiological and biochemical characteristics indicated that
      our strains represent a novel genus and species within the class
      Alphaproteobacteria. The major isoprenoid quinone of the strains was Q-10, the
      major cellular fatty acids were C18 : 1omega7c and 11-methyl C18 : 1omega7c and
      the polar lipid profiles of the strains contained phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and several
      unknown phospholipids and other lipids. The characteristic diamino acid in their
      cell wall was meso-diaminopimelic acid. The G+C content of DNA of the proposed
      type strain PI_21(T) was 68.9 mol%. A new genus and species, Phreatobacter
      oligotrophus gen. nov., sp. nov., is proposed to accommodate the strains. Strain
      PI_21(T) ( = DSM 25521(T) = NCAIM B 02510(T)) is the type strain of Phreatobacter
      oligotrophus. 

PMID- 24277863
TI  - Taxonomic evaluation of Streptomyces albus and related species using multilocus
      sequence analysis and proposals to emend the description of Streptomyces albus
      and describe Streptomyces pathocidini sp. nov.
AB  - In phylogenetic analyses of the genus Streptomyces using 16S rRNA gene sequences,
      Streptomyces albus subsp. albus NRRL B-1811(T) forms a cluster with five other
      species having identical or nearly identical 16S rRNA gene sequences. Moreover,
      the morphological and physiological characteristics of these other species,
      including Streptomyces almquistii NRRL B-1685(T), Streptomyces flocculus NRRL B
      2465(T), Streptomyces gibsonii NRRL B-1335(T) and Streptomyces rangoonensis NRRL
      B-12378(T) are quite similar. This cluster is of particular taxonomic interest
      because Streptomyces albus is the type species of the genus Streptomyces. The
      related strains were subjected to multilocus sequence analysis (MLSA) utilizing
      partial sequences of the housekeeping genes atpD, gyrB, recA, rpoB and trpB and
      confirmation of previously reported phenotypic characteristics. The five strains
      formed a coherent cluster supported by a 100 % bootstrap value in phylogenetic
      trees generated from sequence alignments prepared by concatenating the sequences
      of the housekeeping genes, and identical tree topology was observed using various
      different tree-making algorithms. Moreover, all but one strain, S. flocculus NRRL
      B-2465(T), exhibited identical sequences for all of the five housekeeping gene
      loci sequenced, but NRRL B-2465(T) still exhibited an MLSA evolutionary distance
      of 0.005 from the other strains, a value that is lower than the 0.007 MLSA
      evolutionary distance threshold proposed for species-level relatedness. These
      data support a proposal to reclassify S. almquistii, S. flocculus, S. gibsonii
      and S. rangoonensis as later heterotypic synonyms of S. albus with NRRL B-1811(T)
      as the type strain. The MLSA sequence database also demonstrated utility for
      quickly and conclusively confirming that numerous strains within the ARS Culture
      Collection had been previously misidentified as subspecies of S. albus and that
      Streptomyces albus subsp. pathocidicus should be redescribed as a novel species,
      Streptomyces pathocidini sp. nov., with the type strain NRRL B-24287(T). 

PMID- 24277864
TI  - Transition between fast and slow gamma modes in rat hippocampus area CA1 in vitro
      is modulated by slow CA3 gamma oscillations.
AB  - Hippocampal gamma oscillations have been associated with cognitive functions
      including navigation and memory encoding/retrieval. Gamma oscillations in area
      CA1 are thought to depend on the oscillatory drive from CA3 (slow gamma) or the
      entorhinal cortex (fast gamma). Here we show that the local CA1 network can
      generate its own fast gamma that can be suppressed by slow gamma-paced inputs
      from CA3. Moderate acetylcholine receptor activation induces fast (45 +/- 1 Hz)
      gamma in rat CA1 minislices and slow (33 +/- 1 Hz) gamma in CA3 minislices in
      vitro. Using pharmacological tools, current-source density analysis and
      intracellular recordings from pyramidal cells and fast-spiking stratum pyramidale
      interneurons, we demonstrate that fast gamma in CA1 is of the pyramidal
      interneuron network gamma (PING) type, with the firing of principal cells paced
      by recurrent perisomal IPSCs. The oscillation frequency was only weakly dependent
      on IPSC amplitude, and decreased to that of CA3 slow gamma by reducing IPSC decay
      rate or reducing interneuron activation through tonic inhibition of interneurons.
      Fast gamma in CA1 was replaced by slow CA3-driven gamma in unlesioned slices,
      which could be mimicked in CA1 minislices by sub-threshold 35 Hz Schaffer
      collateral stimulation that activated fast-spiking interneurons but
      hyperpolarised pyramidal cells, suggesting that slow gamma frequency CA3 outputs
      can suppress the CA1 fast gamma-generating network by feed-forward inhibition and
      replaces it with a slower gamma oscillation driven by feed-forward inhibition.
      The transition between the two gamma oscillation modes in CA1 might allow it to
      alternate between effective communication with the medial entorhinal cortex and
      CA3, which have different roles in encoding and recall of memory.

PMID- 24277865
TI  - Phosphatase activity of the voltage-sensing phosphatase, VSP, shows graded
      dependence on the extent of activation of the voltage sensor.
AB  - The voltage-sensing phosphatase (VSP) consists of a voltage sensor and a
      cytoplasmic phosphatase region, and the movement of the voltage sensor is coupled
      to the phosphatase activity. However, its coupling mechanisms still remain
      unclear. One possible scenario is that the phosphatase is activated only when the
      voltage sensor is in a fully activated state. Alternatively, the enzymatic
      activity of single VSP proteins could be graded in distinct activated states of
      the voltage sensor, and partial activation of the voltage sensor could lead to
      partial activation of the phosphatase. To distinguish between these two
      possibilities, we studied a voltage sensor mutant of zebrafish VSP, where the
      voltage sensor moves in two steps as evidenced by analyses of charge movements of
      the voltage sensor and voltage clamp fluorometry. Measurements of the phosphatase
      activity toward phosphatidylinositol 4,5-bisphosphate revealed that both steps of
      voltage sensor activation are coupled to the tuning of phosphatase activities,
      consistent with the idea that the phosphatase activity is graded by the magnitude
      of the movement of the voltage sensor. 

PMID- 24277866
TI  - Intracellular signalling mechanism responsible for modulation of sarcolemmal ATP
      sensitive potassium channels by nitric oxide in ventricular cardiomyocytes.
AB  - The ATP-sensitive potassium (KATP) channels are crucial for stress adaptation in
      the heart. It has previously been suggested that the function of KATP channels is
      modulated by nitric oxide (NO), a gaseous messenger known to be cytoprotective;
      however, the underlying mechanism remains poorly understood. Here we sought to
      delineate the intracellular signalling mechanism responsible for NO modulation of
      sarcolemmal KATP (sarcKATP) channels in ventricular cardiomyocytes. Cell-attached
      patch recordings were performed in transfected human embryonic kidney (HEK) 293
      cells and ventricular cardiomyocytes freshly isolated from adult rabbits or
      genetically modified mice, in combination with pharmacological and biochemical
      approaches. Bath application of the NO donor NOC-18 increased the single-channel
      activity of Kir6.2/SUR2A (i.e., the principal ventricular-type KATP) channels in
      HEK293 cells, whereas the increase was abated by KT5823 [a selective cGMP
      dependent protein kinase (PKG) inhibitor], mercaptopropionyl glycine [MPG; a
      reactive oxygen species (ROS) scavenger], catalase (an H2O2-degrading enzyme),
      myristoylated autocamtide-2 related inhibitory peptide (mAIP) selective for Ca2+
      / calmodulin-dependent protein kinase II (CaMKII) and U0126 [an extracellular
      signal-regulated protein kinase 1/2 (ERK1/2) inhibitor], respectively. The NO
      donors NOC-18 and N-(2-deoxy-alpha,beta-d-glucopyranose-2-)-N2-acetyl-S-nitroso
      d,l-penicillaminamide (glycol-SNAP-2) were also capable of stimulating native
      sarcKATP channels preactivated by the channel opener pinacidil in rabbit
      ventricular myocytes, through reducing the occurrence and the dwelling time of
      the long closed states whilst increasing the frequency of channel opening; in
      contrast, all these changes were reversed in the presence of inhibitors selective
      for soluble guanylyl cyclase (sGC), PKG, calmodulin, CaMKII or ERK1/2. Mimicking
      the action of NO donors, exogenous H2O2 potentiated pinacidil-preactivated
      sarcKATP channel activity in intact cardiomyocytes, but the H2O2-induced KATP
      channel stimulation was obliterated when ERK1/2 or CaMKII activity was
      suppressed, implying that H2O2 is positioned upstream of ERK1/2 and CaMKII for
      K(ATP) channel modulation. Furthermore, genetic ablation (i.e., knockout) of
      CaMKIIdelta, the predominant cardiac CaMKII isoform, diminished ventricular
      sarcK(ATP) channel stimulation elicited by activation of PKG, unveiling
      CaMKIIdelta as a crucial player. Additionally, evidence from kinase activity and
      Western blot analyses revealed that activation of NO-PKG signalling augmented
      CaMKII activity in rabbit ventricular myocytes and, importantly, CaMKII
      activation by PKG occurred in an ERK1/2-dependent manner, placing ERK1/2 upstream
      of CaMKII. Taken together, these findings suggest that NO modulates ventricular
      sarcK(ATP) channels via a novel sGC-cGMP-PKG-ROS(H2O2)-ERK1/2-calmodulin-CaMKII
      (delta isoform in particular) signalling cascade, which heightens K(ATP) channel
      activity by destabilizing the long closed states while facilitating closed-to
      open state transitions. This pathway may contribute to regulation of cardiac
      excitability and cytoprotection against ischaemia-reperfusion injury, in part, by
      opening myocardial sarcK(ATP) channels.

PMID- 24277867
TI  - Purinergic control of vascular tone in the retina.
AB  - Purinergic control of vascular tone in the CNS has been largely unexplored. This
      study examines the contribution of endogenous extracellular ATP, acting on
      vascular smooth muscle cells, in controlling vascular tone in the in vivo rat
      retina. Retinal vessels were labelled by i.v. injection of a fluorescent dye and
      imaged with scanning laser confocal microscopy. The diameters of primary
      arterioles were monitored under control conditions and following intravitreal
      injection of pharmacological agents. Apyrase (500 units ml(-1)), an ATP
      hydrolysing enzyme, dilated retinal arterioles by 40.4 +/- 2.8%, while AOPCP
      (12.5 mm), an ecto-5'-nucleotidase inhibitor that increases extracellular ATP
      levels, constricted arterioles by 58.0 +/- 3.8% (P < 0.001 for both),
      demonstrating the importance of ATP in the control of basal vascular tone.
      Suramin (500 MUm), a broad-spectrum P2 receptor antagonist, dilated retinal
      arterioles by 50.9 +/- 3.7% (P < 0.001). IsoPPADS (300 MUm) and TNP-ATP (50 MUm),
      more selective P2X antagonists, dilated arterioles by 41.0 +/- 5.3% and 55.2 +/-
      6.1% respectively (P < 0.001 for both). NF023 (50 MUm), a potent antagonist of
      P2X1 receptors, dilated retinal arterioles by 32.1 +/- 2.6% (P < 0.001). A438079
      (500 MUm) and AZ10606120 (50 MUm), P2X7 antagonists, had no effect on basal
      vascular tone (P = 0.99 and P = 1.00 respectively). In the ex vivo retina, the
      P2X1 receptor agonist alpha,beta-methylene ATP (300 nm) evoked sustained
      vasoconstrictions of 18.7 +/- 3.2% (P < 0.05). In vivo vitreal injection of the
      gliotoxin fluorocitrate (150 MUm) dilated retinal vessels by 52.3 +/- 1.1% (P <
      0.001) and inhibited the vasodilatory response to NF023 (50 MUm, 7.9 +/- 2.0%; P
      < 0.01). These findings suggest that vascular tone in rat retinal arterioles is
      maintained by tonic release of ATP from the retina. ATP acts on P2X1 receptors,
      although contributions from other P2X and P2Y receptors cannot be ruled out.
      Retinal glial cells are a possible source of the vasoconstricting ATP.

PMID- 24277869
TI  - Progress of sperm IZUMO1 relocation during spontaneous acrosome reaction.
AB  - It has been recently shown in mice that sperm undergo acrosome reaction (AR) by
      passing through cumulus cells; furthermore, the acrosome-reacted sperm can bind
      to zona pellucida and consequently fertilise the egg. During AR, the relocation
      of the primary fusion protein IZUMO1 into the equatorial segment is crucial for
      sperm-egg fusion. There is a high rate of spontaneous AR in rodents, with up to
      60% in promiscuous species. The aim of this study was to clarify whether the
      IZUMO1 relocation in sperm after spontaneous and induced AR is the same, and
      whether there is a correlation between the speed of IZUMO1 relocation and species
      specific mating behaviour in field mice. Immunofluorescent detection of IZUMO1
      dynamics during the in vitro capacitation, spontaneous, calcium ionophore and
      progesterone-induced AR was monitored. Our results show that during spontaneous
      AR, there is a clear IZUMO1 relocation from the acrosomal cap to the equatorial
      segment, and further over the whole sperm head. In addition, there is positive
      tail tyrosine phosphorylation (TyrP) associated with hyperactive motility.
      Moreover, the beginning and the progress of IZUMO1 relocation and tail TyrP
      positively correlate with the level of promiscuity and the acrosome instability
      in promiscuous species. The findings that crucial molecular changes essential for
      sperm-egg fusion represented by dynamic movements of IZUMO1 also happen during
      spontaneous AR are vital for understanding fertilisation in mice. 

PMID- 24277868
TI  - Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure
      susceptibility.
AB  - T-type calcium channels play essential roles in regulating neuronal excitability
      and network oscillations in the brain. Mutations in the gene encoding Cav3.2 T
      type Ca(2+) channels, CACNA1H, have been found in association with various forms
      of idiopathic generalized epilepsy. We and others have found that these mutations
      may influence neuronal excitability either by altering the biophysical properties
      of the channels or by increasing their surface expression. The goals of the
      present study were to investigate the excitability of neurons expressing Cav3.2
      with the epilepsy mutation, C456S, and to elucidate the mechanisms by which it
      influences neuronal properties. We found that expression of the recombinant C456S
      channels substantially increased the excitability of cultured neurons by
      increasing the spontaneous firing rate and reducing the threshold for rebound
      burst firing. Additionally, we found that molecular determinants in the I-II loop
      (the region in which most childhood absence epilepsy-associated mutations are
      found) substantially increase the surface expression of T-channels but do not
      alter the relative distribution of channels into dendrites of cultured
      hippocampal neurons. Finally, we discovered that expression of C456S channels
      promoted dendritic growth and arborization. These effects were reversed to normal
      by either the absence epilepsy drug ethosuximide or a novel T-channel blocker,
      TTA-P2. As Ca(2+)-regulated transcription factors also increase dendritic
      development, we tested a transactivator trap assay and found that the C456S
      variant can induce changes in gene transcription. Taken together, our findings
      suggest that gain-of-function mutations in Cav3.2 T-type Ca(2+) channels increase
      seizure susceptibility by directly altering neuronal electrical properties and
      indirectly by changing gene expression.

PMID- 24277870
TI  - Alternative splicing, promoter methylation, and functional SNPs of sperm flagella
      2 gene in testis and mature spermatozoa of Holstein bulls.
AB  - The sperm flagella 2 (SPEF2) gene is essential for development of normal sperm
      tail and male fertility. In this study, we characterized first the splice
      variants, promoter and its methylation, and functional single-nucleotide
      polymorphisms (SNPs) of the SPEF2 gene in newborn and adult Holstein bulls. Four
      splice variants were identified in the testes, epididymis, sperm, heart, spleen,
      lungs, kidneys, and liver tissues through RT-PCR, clone sequencing, and western
      blot analysis. Immunohistochemistry revealed that the SPEF2 was specifically
      expressed in the primary spermatocytes, elongated spermatids, and round
      spermatids in the testes and epididymis. SPEF2-SV1 was differentially expressed
      in the sperms of high-performance and low-performance adult bulls; SPEF2-SV2
      presents the highest expression in testis and epididymis; SPEF2-SV3 was only
      detected in testis and epididymis. An SNP (c.2851G>T) in exon 20 of SPEF2,
      located within a putative exonic splice enhancer, potentially produced SPEF2-SV3
      and was involved in semen deformity rate and post-thaw cryopreserved sperm
      motility. The luciferase reporter and bisulfite sequencing analysis suggested
      that the methylation pattern of the core promoter did not significantly differ
      between the full-sib bulls that presented hypomethylation in the ejaculated semen
      and testis. This finding indicates that sperm quality is unrelated to SPEF2
      methylation pattern. Our data suggest that alternative splicing, rather than
      methylation, is involved in the regulation of SPEF2 expression in the testes and
      sperm and is one of the determinants of sperm motility during bull
      spermatogenesis. The exonic SNP (c.2851G>T) produces aberrant splice variants,
      which can be used as a candidate marker for semen traits selection breeding of
      Holstein bulls. 

PMID- 24277871
TI  - Total Monte Carlo evaluation for dose calculations.
AB  - Total Monte Carlo (TMC) is a method to propagate nuclear data (ND) uncertainties
      in transport codes, by using a large set of ND files, which covers the ND
      uncertainty. The transport code is run multiple times, each time with a unique ND
      file, and the result is a distribution of the investigated parameter, e.g. dose,
      where the width of the distribution is interpreted as the uncertainty due to ND.
      Until recently, this was computer intensive, but with a new development, fast
      TMC, more applications are accessible. The aim of this work is to test the fast
      TMC methodology on a dosimetry application and to propagate the (56)Fe
      uncertainties on the predictions of the dose outside a proposed 14-MeV neutron
      facility. The uncertainty was found to be 4.2 %. This can be considered small;
      however, this cannot be generalised to all dosimetry applications and so ND
      uncertainties should routinely be included in most dosimetry modelling. 

PMID- 24277872
TI  - Fundamental study on the characteristics of a radiophotoluminescence glass
      dosemeter with no energy compensation filter for measuring patient entrance doses
      in cardiac interventional procedures.
AB  - Cardiac interventional procedures have been increasing year by year. However,
      radiation skin injuries have been still reported. There is a necessity to measure
      the patient entrance skin dose (ESD), but an accurate dose measurement method has
      not been established. To measure the ESD, a lot of radiophotoluminescence
      dosemeters (RPLDs) provide an accurate measurement of the direct actual ESD at
      the points they are arrayed. The purpose of this study was to examine the
      characteristics of RPLD to measure the ESD. As a result, X-ray permeable RPLD
      (with no tin filter) did not interfere with the percutaneous coronary
      intervention procedure. The RPLD also had good fundamental performance
      characteristics. Although the RPLD had a little energy dependence, it showed
      excellent dose and dose-rate linearity, and good angular dependence. In
      conclusion, by calibrating the energy dependence, RPLDs are useful dosemeter to
      measure the ESD in cardiac intervention. 

PMID- 24277873
TI  - Radiation protection performance for the dismantling of the WWR-M primary cooling
      circuit.
AB  - The WWR-M is a light-water-cooled and moderated heterogonous research reactor
      with a thermal output of 10 MW. The reactor has been in operation for >50 y and
      has had an excellent safety record. A non-hermeticity of the inlet line of the
      primary cooling circuit (PCC) was found, and the only reasonable technical
      solution was the complete replacement of the PCC inlet and outlet pipe lines.
      Such a replacement was a challenging technical task due to the necessity to
      handle large size components with complex geometries under conditions of high
      level radiation fields, and therefore, it required detailed planning aiming to
      reduce staff exposure. This paper describes the dismantling and removal of the
      PCC components focusing on radiation protection issues. 

PMID- 24277874
TI  - Compact thermal neutron sensors for moderator-based neutron spectrometers.
AB  - In the framework of the NESCOFI@BTF project of the Italian Institute of Nuclear
      Physics, different types of active thermal neutron sensors were studied by
      coupling semiconductor devices with a suitable radiator. The objective was to
      develop a detector of small dimensions with a proper sensitivity to use at
      different positions in a novel moderating assembly for neutron spectrometry. This
      work discusses the experimental activity carried out in the framework of the
      ERINDA program (PAC 3/9 2012) to characterise the performance of a thermal
      neutron pulse detector based on (6)Li. 

PMID- 24277875
TI  - Fast neutron dosemeter using pixelated detector Timepix.
AB  - A Timepix detector covered with polyethylene convertors of different thicknesses
      is presented as a fast neutron real-time dosemeter. The application of different
      weighting factors in connection with the position of a signal in a Timepix
      detector enables one to obtain an energy-dependent signal equal to neutron dose
      equivalents. A simulation of a Timepix detector covered with polyethylene
      convertors using monoenergetic neutrons is presented. The experimental set-up of
      a dosemeter was also produced. The first results of detector response using
      different fast neutron sources are presented. 

PMID- 24277876
TI  - FastPixN, a new integrated pixel chip for a future fast version of the IRSN -
      recoil proton telescope.
AB  - A first prototype of recoil proton telescope (RPT) is currently working at the
      AMANDE facility, being developed as a collaboration between IPHC Strasbourg and
      the LNE-IRSN. The device, able to measure both energy and fluence of neutron
      fields in the range of 5-20 MeV, has to be improved further, in order to reduce
      the considerable inelastic background generated by the neutrons inside the RPT
      itself. To achieve faster running cycles, the present complementary metal-oxide
      semiconductor pixels used for proton tracking are to be replaced by a new
      integrated chip, specially developed for this application. The authors present a
      first version of this new element, with individual pixels readout at a 200-MHz
      frequency, with a fast 4-bit ADC for each column of 64 pixels. The measured
      performances point to a complete frame treatment in only 12.6 us. With a readout
      speed multiplied by a factor 400 over the existing device, the authors expect a
      considerable improvement of the telescope at AMANDE, with the potential to reach
      neutron fluence rates up to 10(7) n cm(-2) s(-1) or more. 

PMID- 24277881
TI  - Methodology of the third British National Survey of Sexual Attitudes and
      Lifestyles (Natsal-3).
AB  - BACKGROUND: Data from the first two National Surveys of Sexual Attitudes and
      Lifestyles, carried out in 1990-1991 (Natsal-1) and 1999-2001 (Natsal-2), have
      been extensively used to inform sexual health policy in Britain over the past two
      decades. Natsal-3 was carried out from September 2010 to August 2012 in order to
      provide up-to-date measures of sexual lifestyles and to extend the scope of the
      previous studies by including an older age group (up to 74 years), an extended
      range of topics and biological measures. METHODS: We describe the methods used in
      Natsal-3, which surveyed the general population in Britain aged 16-74 years (with
      oversampling of younger adults aged 16-34 years). RESULTS: Overall, 15 162
      interviews were completed, with a response rate of 57.7% and a cooperation rate
      of 65.8%. The response rate for the boost sample of ages 16-34 years was 64.8%,
      only marginally lower than the 65.4% achieved for Natsal-2, which surveyed a
      similar age range (16-44). The data were weighted by age, gender and region to
      reduce possible bias. Comparisons with census data show the weighted sample to
      provide good representation on a range of respondent characteristics. The
      interview involved a combination of face-to-face and self-completion components,
      both carried out on computer. Urine samples from 4550 sexually-experienced
      participants aged 16-44 years were tested for a range of STIs. Saliva samples
      from 4128 participants aged 18-74 years were tested for testosterone.
      CONCLUSIONS: Natsal-3 provides a high quality dataset that can be used to examine
      trends in sexual attitudes and behaviours over the past 20 years.

PMID- 24277882
TI  - Consistency in reporting sensitive sexual behaviours in Britain: change in
      reporting bias in the second and third National Surveys of Sexual Attitudes and
      Lifestyles (Natsal-2 and Natsal-3).
AB  - OBJECTIVES: Britain's second National Survey of Sexual Attitudes and Lifestyles
      (Natsal-2) was conducted in 1999-2001 and the third (Natsal-3) was conducted in
      2010-2012 to update prevalence estimates of sexual behaviours and assess changes
      over time. We investigated whether there was a change in reporting bias between
      these two cross-sectional surveys. METHODS: We analysed data from the 'common
      birth cohort' of participants born during 1956-1983, who were eligible to take
      part in Natsal-2 (n=10 764) and Natsal-3 (n=6907). We compared estimates for
      outcomes that occurred before Natsal-2 and expected these to be consistent
      between surveys if no change in reporting bias had occurred. RESULTS: A greater
      proportion of non-white men and women were in Natsal-3 consistent with
      demographic changes in Britain. Reporting behaviours was largely consistent
      between surveys for men. Fewer women in Natsal-3 reported early first intercourse
      or having child(ren) before age 20; they were also more likely to report not
      discussing sex with their parents at age 14. Men and women in Natsal-3 were more
      likely to report tolerant attitudes towards same-sex partnerships but less
      tolerance towards unfaithfulness in marriage and one-night-stands. CONCLUSIONS:
      We found little evidence of change in reporting bias among men since Natsal-2.
      Among women, a modest change in reporting bias was observed for a small number of
      experiences, possibly due to changes in participation, social acceptability and
      methodological differences between surveys. Changes in the reporting of sexual
      behaviours and attitudes over time observed in the wider Natsal-3 study are
      therefore likely to largely reflect real changes in the population.

PMID- 24277883
TI  - Various complications of percutaneous radiofrequency ablation for hepatic tumors:
      radiologic findings and technical tips.
AB  - Radiofrequency ablation is a safe and effective treatment for primary and
      secondary liver malignancies and has a low complication rate; however, there are
      various radiofrequency ablation-related complications which can occur from the
      thorax to the pelvis. Although most of these complications are usually minor and
      self-limited, they may become fatal if diagnosis and treatment are delayed. It is
      important for radiologists performing radiofrequency ablation to have a
      perspective regarding the possible radiofrequency ablation-related complications
      and their risk factors as well as the radiologic findings for their timely
      detection and increase of the treatment efficacy, and thereby encouraging the use
      of the radiofrequency ablation technique. This article illustrates the various
      imaging features of common and rare radiofrequency ablation-related complications
      as well as offers technical tips in order to avoid these complications. 

PMID- 24277884
TI  - Contrast enhancement in bladder tumors examined with CT urography using
      traditional scan phases.
AB  - BACKGROUND: Bladder assessment in an early contrast-enhancing computed tomography
      urography (CTU) phase requires that bladder tumors be enhanced using contrast
      material. PURPOSE: To investigate the enhancement pattern in bladder tumors using
      a CTU protocol where the scan is enhancement triggered. MATERIAL AND METHODS:
      Fifty patients diagnosed with bladder cancer were examined during the unenhanced
      (UP), corticomedullary (CMP), and excretory phases (EP). Twenty-one patients, all
      aged 50 years or older, were also examined during the nephrographic phase (NP). A
      ROI placed in the aorta was used to start the scan during the CMP when the
      attenuation reached 200 Hounsfield units (HU). The NP and EP were started with a
      40 s and 300 s delay, respectively, after the CMP was finished. Attenuation and
      size measurements were made in the axial plane. RESULTS: Mean contrast
      enhancement of bladder tumors was 37, 25, and 17 HU in the CMP, NP, and EP,
      respectively. The differences in contrast enhancement were significant across all
      three phases. Eighty-eight percent of patients showed the highest contrast
      enhancement in the CMP. In 96% of the cases, contrast enhancement >20 HU was
      seen. The mean value of the shortest dimension of the bladder tumors was 22 +/-
      12 mm. CONCLUSION: The contrast enhancement is significantly higher in the CMP
      than in the NP and EP, suggesting that the CMP is preferable when assessing the
      bladder in the early contrast enhancing phase.

PMID- 24277885
TI  - Value of spontaneous hyperdensity of cerebral venous thrombosis on helical CT.
AB  - BACKGROUND: Excluding a cerebral venous thrombosis (CVT) through imaging is a
      frequent request in the emergency setting. This assessment often starts by an
      unenhanced brain computed tomography (CT). PURPOSE: Re-evaluate the value of
      spontaneous hyperdensity of CVT on helical unenhanced brain CT. METHODS:
      Multicentric retrospective study on CVT probability based on visual assessment of
      spontaneous hyperdensity of cerebral venous system, performed by four blinded
      radiologists, individually then collectively, on a population including 14
      helical unenhanced brain CTs with CVT and 102 unenhanced brain CTs without CVT
      (all confirmed by CT or magnetic resonance [MR] venography). Exclusion criteria:
      no DICOM image, symptoms >15 days, CVT indirect signs on unenhanced CT. A fifth
      radiologist set 768 regions of interest to measure and to compare the density
      within the normal venous sinuses and the CVTs. RESULTS: After consensus reading,
      sensitivity of this sign for CVT diagnosis was 100%, specificity 95.1%, and
      negative predictive value (NPV) 100%, with high individual NPV (99-100%). Area
      under the receiver-operating characteristic curve was 0.992 after consensus
      (0.976-0.986 individually). The spontaneous density was significantly different
      (P <0.05) between normal sinuses and CVTs, with a density >70 HU reported only
      within the CVTs, except for the horizontal part of the superior sagittal sinus
      (hSSS). CONCLUSION: The dense triangle sign on helical unenhanced brain CT has an
      excellent NPV to exclude a sinus thrombosis during the first 2 weeks. However, we
      believe that visual assessment of spontaneous hyperdensity is not sufficient for
      the diagnosis of CVT, with possible false-positive of the hSSS on unenhanced CT.

PMID- 24277886
TI  - Predicting coverage of transverse subcostal sonography with the use of previous
      computed tomography before a sonographic liver examination: a prospective study.
AB  - OBJECTIVES: The purpose of this study was to assess the coverage of transverse
      subcostal sonography in the supine position by using computed tomography (CT)
      performed before a sonographic liver examination as a predictor of sonographic
      coverage. METHODS: A total of 124 patients (87 men and 37 women; mean age, 55.55
      years; range, 24-79 years) who underwent abdominal CT and subsequent liver
      sonography were enrolled. All patients were assessed for the coverage of
      transverse subcostal sonography in the supine position by consensus of 2
      radiologists. We evaluated the correlation between the level of the posterior rib
      against the liver dome on axial CT and a sonographic coverage scoring system
      using Spearman partial correlation analysis. The optimal cutoff value of the
      liver position and other potential factors associated with sonographic coverage
      were analyzed. RESULTS: Among age, sex, body mass index, interposition of bowel
      around the gallbladder fossa, atrophic changes from cirrhotic liver, and liver
      position, liver position was the only independent factor associated with
      sonographic coverage (P < .001). Liver position and the sonographic coverage
      score were moderately negatively correlated, with statistical significance (r = 
      0.44; P < .001). The optimal cutoff value for the level of the hepatic dome was
      at the 10th posterior rib on axial CT. CONCLUSIONS: Liver position is the only
      independent factor associated with the coverage of transverse subcostal
      sonography in the supine position. If it is above the 10th posterior rib level,
      we can predict difficulty in adequate sonographic coverage of the liver.

PMID- 24277887
TI  - Assessment of left ventricular diastolic dysfunction based on the
      intraventricular velocity difference by vector flow mapping.
AB  - OBJECTIVES: The diastolic intraventricular velocity difference represents
      diastolic function of the left ventricle (LV). Here we analyzed the LV diastolic
      intraventricular velocity difference in patients with impaired LV function based
      on the ventricular flow rate profile by vector flow mapping. METHODS: Patients
      with LV diastolic dysfunction were divided into 2 groups: chronic heart failure
      with restricted filling (group 1; n = 27) and hypertension with abnormal
      relaxation (group 2; n = 34). Healthy participants were identified as controls
      (group 3; n = 22). Left ventricular inflow color Doppler findings were analyzed
      by the vector profile model with the vector flow mapping technology offline. The
      flow velocity rates at the base and apex of the LV were measured from vector
      profiles with the vector flow mapping technology. The diastolic intraventricular
      velocity difference was calculated from flow velocity rates. RESULTS: The
      diastolic intraventricular velocity difference calculated from vector flow
      mapping was significantly lower in both groups with LV diastolic dysfunction than
      the control group (mean +/- SD, 79.95 +/- 9.88 cm/s in controls versus 40.35 +/-
      6.80 cm/s in group 1 and 48.50 +/- 6.03 cm/s in group 2; P < .001 for both). The
      diastolic intraventricular velocity difference had a significant association with
      the ejection fraction (P = .0002) and deceleration time (P = .0306). The peak
      atrial contraction velocity was negatively related to the diastolic
      intraventricular velocity difference (P = .0003). CONCLUSIONS: The diastolic
      intraventricular velocity difference derived from the LV velocity rate by the
      vector profile model on vector flow mapping can be potentially used for
      quantitative assessment of LV diastolic function. Vector flow mapping proved to
      be clinically practical for reflecting LV diastolic dysfunction in pathologic
      states.

PMID- 24277888
TI  - Distal pectoralis major tears: sonographic characterization and potential
      diagnostic pitfalls.
AB  - OBJECTIVES: Distinction between musculotendinous tears of the pectoralis major
      and distal tendon avulsions is important, as the latter typically requires
      surgical repair. The objective of this study was to characterize the sonographic
      appearances of surgically proven distal tendon avulsion tears of the pectoralis
      major. METHODS: A retrospective search of the radiology database (2001-2011)
      revealed 22 cases of pectoralis major tears on sonography, of which 9 had
      surgical correlation. Sonograms were retrospectively characterized by 3
      fellowship-trained musculoskeletal radiologists in consensus with respect to the
      location and size of the fluid collection and the presence of tendon or
      tendonlike tissue superficial to the biceps brachii tendon. RESULTS: At surgery,
      complete distal tendon avulsions or tears of the sternal head of the pectoralis
      were present in all 9 cases: isolated in 6 and combined with clavicular head
      tears in 3. The location of the fluid collection was at the musculotendinous
      junction in 89% (8 of 9) and medial to the biceps brachii tendon in 11% (1 of 9),
      with a mean largest dimension of 3.8 cm (range, 0.7-6.2 cm). In no case was fluid
      seen at the humeral attachment of the pectoralis. In 67% (6 of 9), linear
      thickened hypoechoic tissue was seen superficial to the biceps brachii tendon,
      which simulated an abnormal but intact tendon, whereas in 33% (3 of 9), a normal
      distal pectoralis tendon was seen. CONCLUSIONS: Surgically proven distal
      pectoralis major tendon avulsions most commonly showed fluid collections at the
      musculotendinous junction and not at the humeral shaft, with either a normal
      tendon or hypoechoic tendonlike tissue over the biceps brachii long-head tendon.
      These findings may potentially cause misdiagnosis of distal tendon avulsions or
      tears as musculotendinous injuries.

PMID- 24277889
TI  - Sonographically guided costotransverse joint injections: a computed
      tomographically controlled cadaveric feasibility study.
AB  - OBJECTIVES: The primary purpose of this study was to describe and validate a
      novel sonographically guided costotransverse (CTRV) joint injection technique.
      METHODS: The bilateral T3-T10 CTRV joints of an unembalmed cadaveric specimen
      were localized using a 12-3-MHz linear array transducer. A 22-gauge, 2.5-in
      spinal needle was directed into the CTRV joint using an in-plane, lateral-to
      medial approach under direct sonographic guidance. After needle placement, 3
      dimensional computed tomographic (CT) images were obtained to assess the
      locations of the needle tips. This step was followed by injection of an iodinated
      contrast agent and repeated CT to assess the contrast flow pattern. An
      experienced musculoskeletal radiologist reviewed the CT images and assessed the
      accuracy of the injections (intra- or extra-articular). For intra-articular
      injections, a quantitative assessment of the percentage of injectate within the
      joint was performed. RESULTS: A total of 16 sonographically guided CTRV joint
      injections were completed on a single torso-pelvis specimen. Using our technique,
      11 of 16 sonographically guided CTRV joint injections (68.8%) placed the contrast
      agent into the target joint. Quantitative analysis of the arthrograms showed 6 of
      11 intra-articular injections (54.5%) with greater than 50% injectate within the
      joint capsule. CONCLUSIONS: To our knowledge, this study is the first to
      determine the feasibility of sonographically guided CTRV joint injections.
      Overall, 68.8% of injection attempts produced acceptable CTRV joint arthrograms,
      which compares favorably to a previously reported 76% accuracy rate for
      fluoroscopically guided CTRV joint injections. Although these injections are
      technically challenging, the use of sonographic guidance to perform CTRV joint
      injections is feasible and warrants further investigation to establish its role
      in the management of patients presenting with thoracic pain syndromes.

PMID- 24277890
TI  - High-resolution median nerve sonographic measurements: correlations with median
      nerve conduction studies in healthy adults.
AB  - OBJECTIVES: To study relationships between median wrist and forearm sonographic
      measurements and median nerve conduction studies. METHODS: The study population
      consisted of a prospective convenience sample of healthy adults. Interventions
      included high-resolution median nerve sonography and median motor and sensory
      nerve conduction studies. Main outcome measures included median motor nerve
      compound muscle action potential amplitude, distal latency, and conduction
      velocity; sensory nerve action potential amplitude and distal latency; and
      sonographic median nerve cross-sectional area. Median motor nerve and sensory
      nerve conduction studies of the index finger were performed using standard
      published techniques. A second examiner blinded to nerve conduction study results
      used a high-frequency linear array transducer to measure the cross-sectional area
      of the median nerve at the distal volar wrist crease (carpal tunnel inlet) and
      forearm (4 cm proximally), measured in the transverse plane on static sonograms.
      The outer margin of the median nerve was traced at the junction of the hypoechoic
      fascicles and adjacent outer connective tissue layer. RESULTS: Fifty median
      nerves were evaluated in 25 participants. The compound muscle action potential
      amplitude with wrist stimulation was positively related to the cross-sectional
      area, with the area increasing by 0.195 mm(2) for every millivolt increase in
      amplitude in the dominant hand (95% confidence interval, 0.020, 0.370 mm(2); P <
      .05) and 0.247 mm(2) in the nondominant hand (95% confidence interval, 0.035,
      0.459 mm(2); P < .05). There was no significant linear association between the
      wrist median cross-sectional area and median motor and sensory distal latencies.
      Conduction velocity through the forearm was not significantly linearly associated
      with the forearm area or forearm-to-wrist area ratio (tapering ratio). The wrist
      area was inversely related to the sensory nerve action potential amplitude.
      CONCLUSIONS: Although associations were found between median nerve conduction
      study amplitudes and sonographic nerve measurements, they were not found for
      other parameters. Studying these relationships may increase our understanding of
      when to best use these procedures.

PMID- 24277891
TI  - Focused physician-performed echocardiography in sports medicine: a potential
      screening tool for detecting aortic root dilatation in athletes.
AB  - OBJECTIVES: The purpose of this study was to investigate whether sports medicine
      physicians can obtain accurate measurements of the aortic root in young athletes.
      METHODS: Twenty male collegiate athletes, aged 18 to 21 years, were prospectively
      enrolled. Focused echocardiography was performed by a board-certified sports
      medicine physician and a medical student, followed by comprehensive
      echocardiography within 2 weeks by a cardiac sonographer. A left parasternal long
      axis view was acquired to measure the aortic root diameter at the sinuses of
      Valsalva. Intraclass correlation coefficients (ICCs) were used to assess inter
      rater reliability compared to a reference standard and intra-rater reliability of
      repeated measurements obtained by the sports medicine physician and medical
      student. RESULTS: The ICCs between the sports medicine physician and cardiac
      sonographer and between the medical student and cardiac sonographer were strong:
      0.80 and 0.76, respectively. Across all 3 readers, the ICC was 0.89, indicating
      strong inter-rater reliability and concordance. The ICC for the 2 measurements
      taken by the sports medicine physician for each athlete was 0.75, indicating
      strong intra-rater reliability. The medical student had moderate intra-rater
      reliability, with an ICC of 0.59. CONCLUSIONS: Sports medicine physicians are
      able to obtain measurements of the aortic root by focused echocardiography that
      are consistent with those obtained by a cardiac sonographer. Focused physician
      performed echocardiography may serve as a promising technique for detecting
      aortic root dilatation and may contribute in this manner to preparticipation
      cardiovascular screening for athletes.

PMID- 24277892
TI  - Third-trimester abnormal uterine artery Doppler findings are associated with
      adverse pregnancy outcomes.
AB  - OBJECTIVES: To evaluate the association between third-trimester abnormal uterine
      artery Doppler findings and pregnancy outcomes. METHODS: A prospective study was
      designed, including 198 consecutive singleton pregnancies between 27 and 41
      weeks' gestation. In the study population, 144 had normal uterine artery Doppler
      waveforms, 37 had unilateral pathologic waveforms, and 17 had bilateral
      pathologic waveforms. Eighty patients had intrauterine growth restriction (IUGR),
      preeclampsia toxemia, or both, and 118 had no complications and served as a
      control group. The uterine artery Doppler waveform was considered abnormal when a
      notch or pulsatility index above the 90th percentile was noted. RESULTS: In
      patients with bilateral pathologic uterine artery Doppler waveforms, the rates of
      cesarean delivery, small-for-gestational-age (SGA) neonates, preterm delivery,
      and low Apgar scores were increased compared to patients with normal or
      pathologic unilateral waveforms (P = .009; P > .001; P = .007; P > .001,
      respectively). The incidence rates for SGA neonates, cesarean delivery, and
      preterm delivery were significantly higher among patients without IUGR or
      preeclampsia toxemia when associated with pathologic bilateral waveforms in
      comparison to normal waveforms (P = .01 for all). A bilateral pathologic waveform
      was found to be an independent risk factor for cesarean delivery and SGA
      neonates. The incidence rates for SGA neonates and preterm delivery were
      significantly higher among patients with IUGR and/or preeclampsia toxemia when
      associated with bilateral abnormalities in comparison to normal waveforms (P =
      .01 for both). CONCLUSIONS: Third-trimester abnormal uterine artery Doppler
      findings are associated with worse perinatal outcomes among patients both with
      and without pregnancy complications.

PMID- 24277893
TI  - Twin reversed arterial perfusion sequence: a new method of parabiotic twin mass
      estimation correlated with pump twin compromise.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that using the
      formula of a prolate ellipsoid to estimate parabiotic twin mass correlates better
      with findings of pump twin compromise than using the sonographic method of Moore
      et al (Am J Obstet Gynecol 1990; 163:907-912). METHODS: A 10-year retrospective
      review was performed to identify all cases of the suspected twin reversed
      arterial perfusion (TRAP) sequence. Parabiotic twin mass was estimated by summing
      body and extremity volumes calculated using the prolate ellipsoid formula (width
      * height * length * 0.523). Parabiotic twin mass was also estimated using the
      sonographic Moore method [1.21 * length(2) - (1.66 * length)]. Parabiotic twin
      mass estimated by both methods was correlated with sonographic findings
      associated with increased risk of pump twin compromise. RESULTS: Fifty-nine
      pregnancies complicated by TRAP were identified. Using the prolate ellipsoid
      formula, the parabiotic twin mean sizes +/- SD (as a percentage of pump twin
      weight) were 103.0% +/- 52.0% and 56.9% +/- 44.3% in cases with and without pump
      twin compromise (P = .0005), respectively. Using the sonographic Moore method,
      the mean parabiotic twin sizes were 122.9% +/- 54.3% and 99.6% +/- 62.8% in cases
      with and without pump twin compromise (P = .14). The median estimated masses of
      the parabiotic twin were 197 +/- 219 g using the prolate ellipsoid formula and
      310 +/- 212 g using the sonographic Moore method (P = .0001). A parabiotic twin
      size greater than 70% of the pump twin correlated with findings associated with
      increased risk of pump twin compromise when using the prolate ellipsoid formula
      (P = .002) but not the sonographic Moore method (P = .09). CONCLUSIONS:
      Sonographic findings associated with increased risk of pump twin compromise
      correlate better with prolate ellipsoid estimates of parabiotic twin mass. The
      median estimated mass of the parabiotic twin was statistically larger when
      calculated by the sonographic Moore method than by the prolate ellipsoid formula.

PMID- 24277894
TI  - Comparison of fetal cardiac spatiotemporal image correlation segmental analysis
      between cardiac- and body-based scrolling.
AB  - OBJECTIVES: The purpose of this study was to compare success rates for depiction
      of the 5 typical transverse planes in the fetal upper thorax between cardiac- and
      body-based scrolling techniques. METHODS: Spatiotemporal image correlation volume
      data sets acquired at the 4-chamber view level were obtained from low-risk
      singleton pregnancies with healthy fetuses. Each data set was analyzed by the
      authors using both cardiac- and body-based techniques. With the cardiac-based
      technique, the exact 4-chamber view was first identified as an initial plane
      before scrolling, whereas with the body-based technique, a volume data set was
      first manipulated to get the fetal orientation in the exact dorsal supine
      position as an initial plane. In both techniques, the volumes were then scrolled
      through the upper thorax to identify the standard planes, including the 4
      chamber, 5-chamber, 3-vessel, 3-vessel and trachea, and aortic arch views.
      RESULTS: An analysis of 50 volume data sets to evaluate intraobserver and
      interobserver variability in the success rates for the 4-chamber, 5-chamber, 3
      vessel, 3-vessel and trachea, and aortic arch views showed good agreement. In an
      analysis of 296 separate data sets, cardiac-based scrolling was associated with
      significantly higher success rates than body-based scrolling in all standard
      planes (P < .05). CONCLUSIONS: Cardiac-based scrolling resulted in higher success
      rates for obtaining the standard spatiotemporal image correlation planes than
      body-based scrolling. Therefore, examiners in the early part of the learning
      curve should be encouraged to first identify a perfect 4-chamber view at the
      start of an examination.

PMID- 24277895
TI  - Absent fetal nasal bone: what does it mean for the euploid fetus?
AB  - OBJECTIVES: Our purpose was to review the outcomes of singleton pregnancies in
      which an absent nasal bone was noted on first- or second-trimester sonography and
      aneuploidy was not present. METHODS: We identified singleton pregnancies from
      2005 to 2011 in which an absent nasal bone was noted on sonography, aneuploidy
      was excluded, and newborn examinations were available for review. Sonographic
      reports were reviewed for anomalies, growth, and amniotic fluid volume. Newborn
      records were reviewed for physical examinations, complications, and radiologic or
      genetic tests. RESULTS: We identified 142 fetuses with a sonographic appearance
      of an absent nasal bone. We excluded 52 cases with aneuploidy and 33 in which
      newborn examination information was unavailable. Fifty-seven cases met inclusion
      criteria. For 3 euploid fetuses with an absent nasal bone on sonography, the
      presence of additional anomalies on second-trimester sonography ultimately
      signaled an adverse outcome: the presence of multiple congenital anomalies, a
      microdeletion syndrome, and a specific genetic diagnosis. CONCLUSIONS: All cases
      with adverse outcomes had additional prenatal sonographic findings. For the
      remainder, normal newborn examination findings provide some reassurance,
      especially in the setting of otherwise normal second-trimester sonographic
      findings. A microarray as a test for microdeletion and duplication syndromes in
      this situation could be considered.

PMID- 24277896
TI  - Charts for fetal age assessment based on fetal sonographic biometry in a
      population from Cali, Colombia.
AB  - OBJECTIVES: To create reference charts for fetal age assessment based on fetal
      sonographic biometry in a population of pregnant women living in the third
      largest city in Colombia and compare them with charts included in ultrasound
      machines. METHODS: The study data were obtained from women with a single
      pregnancy and confirmed gestational age between 12 and 40 completed weeks. All
      women were recruited specifically for the study, and every fetus was measured
      only once for biparietal diameter, head circumference, abdominal circumference,
      and femur length. Polynomial regression models for gestational age as a function
      of each fetal measurement were fitted to estimate the mean and standard
      deviation. Percentile curves of gestational age were constructed for each fetal
      measurement using these regression models. RESULTS: Biparietal diameter, head
      circumference, abdominal circumference, and femur length were measured in 792
      fetuses. Tables and charts of gestational age were derived for each fetal
      parameter. A cubic polynomial model was the best-fitted regression model to
      describe the relationships between gestational age and each fetal measurement.
      The standard deviation was estimated by simple linear regression as a function of
      each fetal measurement. Comparison of our gestational age mean z scores with
      those calculated by reference equations showed statistically significant
      differences (P < .01). CONCLUSIONS: We present a set of reference charts, tables,
      and formulas for fetal age assessment based on fetal sonographic biometry. The
      results support the recommendation that these charts and tables could be more
      appropriate for assessing fetal age in Colombian populations than those currently
      included in the software of ultrasound machines.

PMID- 24277897
TI  - Sonographic findings predictive of central lymph node metastasis in patients with
      papillary thyroid carcinoma: influence of associated chronic lymphocytic
      thyroiditis on the diagnostic performance of sonography.
AB  - OBJECTIVES: To analyze sonographic findings suggesting central lymph node
      metastasis of papillary thyroid carcinoma and to evaluate the influence of
      associated chronic lymphocytic thyroiditis on the diagnostic performance of
      sonography for predicting central lymph node metastasis. METHODS: A total of 124
      patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years)
      underwent sonographically guided fine-needle aspiration in central lymph nodes
      from January 2008 to July 2011. Sonographic features of size, shape, margin,
      thickening of the cortex, cortical echogenicity, presence of a hilum, cystic
      changes, calcification, and vascularity of enlarged lymph nodes were analyzed
      before fine-needle aspiration and classified into 2 categories (probably benign
      and suspicious). Sonographic findings were correlated with the pathologic
      diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating
      characteristic curve analysis was performed to assess the diagnostic performance
      of sonography for predicting central lymph node metastasis according to the
      associated thyroiditis. RESULTS: Fifty-one lymph nodes (39.5%) were malignant,
      and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical
      thickening, cortical echogenicity, cystic changes, calcification, and vascularity
      were significantly different between the benign and metastatic nodes (P < .05).
      On multivariate analysis, eccentric cortical thickening (odds ratio, 26.59; 95%
      confidence interval [CI], 3.26-216.66) and hyper echogenicity of the cortex (odds
      ratio, 18.46; 95% CI, 2.44-139.64) were significantly associated with malignant
      nodes (P < .05). The area under the curve values for sonography for predicting
      metastasis were 0.756 (95% CI, 0.618-0.894) in chronic lymphocytic thyroiditis
      positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients.
      CONCLUSIONS: Eccentric cortical thickening and cortical hyperechogenicity were
      the sonographic findings predictive of central lymph node metastasis from
      papillary thyroid carcinoma. The diagnostic performance of sonography for
      predicting metastasis was superior in chronic lymphocytic thyroiditis-negative
      patients than in positive patients.

PMID- 24277898
TI  - Low nondiagnostic rate for fine-needle capillary sampling biopsy of thyroid
      nodules: a singular experience.
AB  - OBJECTIVES: This study examined the hypothesis that sonographically guided fine
      needle capillary thyroid biopsies performed by an experienced operator and with
      constant technique on nodules that meet the Society of Radiologists in Ultrasound
      criteria warranting biopsy can result in a nondiagnostic rate that is
      significantly lower than prior published reports. METHODS: We retrospectively
      reviewed the sonographic and pathologic reports from 228 consecutive
      sonographically guided fine-needle capillary thyroid biopsies performed during a
      3-year interval by a single operator with more than 15 years of experience
      performing fine-needle capillary thyroid biopsies. There were no exclusion
      criteria. Sonographic and pathologic reports from all nodules biopsied were
      included in the analysis. The radiologist's protocol included 6 fine-needle
      capillary biopsies, each with 20 passes of the needle into the periphery and/or
      solid components of the nodule. The cytologic specimens were reviewed off-site in
      adherence with the Bethesda system for reporting thyroid cytopathologic findings
      and classified as diagnostic or nondiagnostic. The nondiagnostic rate in this
      study was compared with the nondiagnostic rates in prior published reports.
      RESULTS: Among the 228 fine-needle capillary thyroid biopsies performed during
      the study interval, cytologic analysis showed 1 nondiagnostic biopsy, yielding a
      nondiagnostic rate of 0.4%. This rate was significantly lower than previously
      published reports (P < .001). CONCLUSIONS: Sonographically guided fine-needle
      capillary biopsies of the thyroid performed by an experienced radiologist can
      result in a nondiagnostic rate of less than 1%. This finding warrants further
      investigation into the reasons for the discrepancy between the results of this
      study and other previous reports.

PMID- 24277899
TI  - Shear wave elastography for differentiation of benign and malignant thyroid
      nodules: a meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to assess the performance of shear wave
      elastography for identification of benign and malignant thyroid nodules using
      meta-analysis. METHODS: PubMed, MEDLINE, Embase, the Cochrane Library, and the
      China National Knowledge Infrastructure were searched. Patients' clinical
      characteristics, sensitivity, specificity, positive predictive value, and
      negative predictive value were extracted. The diagnostic odds ratio and summary
      receiver operating characteristic curve were used to examine the accuracy of
      shear wave elastography. A meta-analysis was performed to evaluate the clinical
      utility of shear wave elastography for identification of benign and malignant
      thyroid nodules. RESULTS: The summary sensitivity and specificity for the
      diagnosis of malignant thyroid nodules by shear wave elastography were 0.84 (95%
      confidence interval [CI], 0.76-0.90) and 0.90 (95% CI, 0.87-0.92), respectively.
      The pooled positive likelihood ratio was 7.39 (95% CI, 4.09-13.35), and the
      negative likelihood ratio was 0.20 (95% CI, 0.13-0.29). The summary diagnostic
      odds ratio was 41.35 (95% CI, 17.38-98.41), and the summary area under the
      receiver operating characteristic curve was 0.92 (Q* = 0.8538). CONCLUSIONS:
      Shear wave elastography has high sensitivity and specificity in the evaluation of
      thyroid nodules and can potentially reduce unnecessary fine-needle aspiration
      biopsies.

PMID- 24277900
TI  - Application of real-time ultrasound elastography for differential diagnosis of
      breast tumors.
AB  - OBJECTIVES: The purpose of this study was to explore the clinical value of real
      time ultrasound elastography in differentiating malignant from benign breast
      tumors and to determine an optimal cutoff for the traced area ratio by receiver
      operator characteristic (ROC) analysis for differential diagnosis between
      malignant and benign breast masses. METHODS: From October 2010 to June 2011, 102
      patients with 192 breast tumors were enrolled. Conventional sonograms and real
      time elastograms were obtained from the patients. The sensitivity, specificity,
      and accuracy rates for sonography and elastography were calculated, and an ROC
      analysis was performed. RESULTS: Tumors with an elasticity grade of 4 or higher
      were defined as malignant. The sensitivity, specificity, and accuracy of
      elastography were 92.65%, 73.39%, and 81.25%, respectively. These values were
      similar to those for conventional sonography. However, when the techniques were
      combined, the sensitivity, specificity, and accuracy increased to 88.23%, 95.97%,
      and 93.23%. A value of 1.65 was determined to be the traced area ratio cutoff by
      the ROC analysis and was used in this study for differential diagnosis. The
      sensitivity, specificity, and accuracy of this value were 76.47%, 96.77%, and
      89.58%, respectively. CONCLUSIONS: Both conventional sonography and ultrasound
      elastography could be used to differentiate malignant and benign breast tumors.
      If these techniques were combined, the diagnostic values would improve. In
      addition, a traced area ratio of 1.65 could be used as a cutoff to differentiate
      benign and malignant breast tumors.

PMID- 24277901
TI  - Comparison of sonography with sonographically guided fine-needle aspiration
      biopsy and core-needle biopsy for initial axillary staging of breast cancer.
AB  - OBJECTIVES: The purpose of this study was to determine the roles of sonography
      and sonographically guided fine-needle aspiration biopsy and core-needle biopsy
      for initial axillary staging of breast cancer. METHODS: Of 220 patients with
      breast cancer who underwent preoperative or prechemotherapy sonography for
      axillary staging, 52 patients who underwent sonographically guided fine-needle
      aspiration biopsy and core-needle biopsy for cortical thickening or a compressed
      hilum of lymph nodes on sonography were prospectively enrolled. Sonography and
      fine-needle aspiration biopsy/core-needle biopsy findings were compared with
      final pathologic results from sentinel lymph node biopsy or axillary lymph node
      dissection. RESULTS: Forty-eight patients met the final study criteria; we
      excluded 4 who had received primary systemic chemotherapy and showed negative
      fine-needle aspiration biopsy/core-needle biopsy results and negative final
      postoperative pathologic results. The positive predictive value of axillary
      sonography was 54%. The sensitivity and specificity of fine-needle aspiration
      biopsy were 73% and 100%, respectively, and those of core-needle biopsy were 77%
      and 100%. Results did not differ significantly between sonographically guided
      core-needle biopsy and fine-needle aspiration biopsy. The complication rates of
      fine-needle aspiration biopsy and core-needle biopsy were both 4%, and fine
      needle aspiration biopsy and core-needle biopsy cost $180 and $350, respectively.
      CONCLUSIONS: Both sonographically guided fine-needle aspiration biopsy and core
      needle biopsy were useful for axillary staging of breast cancer with high
      sensitivity. However, fine-needle aspiration biopsy is recommended based on the
      advantages of low cost and minimal invasiveness.

PMID- 24277902
TI  - Automated B-line scoring on thoracic sonography.
AB  - With the proliferation of portable sonography and the increase in nontraditional
      users, there is an increased need for automated decision support to standardize
      results. We developed algorithms to evaluate the presence or absence of "B-lines"
      on thoracic sonography as a marker for interstitial fluid. Algorithm performance
      was compared against an average of scores from 2 expert clinical sonographers. On
      the set for algorithm development, 90% of the scores matched the average expert
      scores with differences of 1 or less. On the independent set, a perfect match was
      achieved. We believe that these are the first reported results in computerized B
      line scoring. 

PMID- 24277903
TI  - Sonographically guided lumbar puncture in pediatric patients.
AB  - Our aim with this study was to develop a user-friendly method for pediatric
      sonographically guided lumbar punctures so that we can visualize intrathecal
      anatomy, confirm intrathecal injection at the time of injection, and, most
      importantly, avoid ionizing radiation to a child's already radiosensitive pelvis.
      Sonographically guided lumbar puncture was prospectively performed in children
      aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to
      identify relevant anatomy (including the conus in children 10 years and younger),
      confirm intrathecal injection, visualize intrathecal hematoma, and avoid
      radiation. Sonography is a promising modality for image-guided lumbar punctures
      without radiation in children. 

PMID- 24277904
TI  - Sternal pseudotumor of childhood: don't touch the lesion.
AB  - The common approach to rapidly growing peristernal lesions in young infants is
      oncologic consultation, imaging, and early tissue diagnosis. We represent 3 such
      cases with unique sonographic findings favoring nonaggressive lesions named self
      limiting sternal tumors of childhood, in which a conservative approach of
      sonographic follow-up was chosen. We review the typical sonographic
      characteristics in this rather new and rare entity, separating it from the more
      aggressive group of lesions in this location and age group, and suggest that the
      classic appearance should imply a wait-and-see approach, with sonographic follow
      up studies rather than invasive intervention. 

PMID- 24277905
TI  - Prenatal diagnosis of torcular herophili thrombosis: report of 2 cases and review
      of the literature.
AB  - Prenatally diagnosed thrombosis of the torcular herophili is very rare, and it is
      sometimes misdisgnosed due to unfamiliarity. Sonography with color Doppler
      imaging is the key imaging modality for prenatal diagnosis of torcular herophili
      thrombosis. Typical prenatal sonographic findings include a well-defined
      triangular anechoic collection in the occipital region and an echogenic structure
      within the collection, which represents the thrombus. Fetal magnetic resonance
      imaging is usually used as an adjunctive modality for prenatal diagnosis, as it
      confirms the diagnosis by providing more precise anatomic information and better
      characterization of the lesion. We present 2 cases of thrombosis of an ectatic
      torcular herophili with serial sonographic and magnetic resonance imaging
      examinations, as well as a review of the literature regarding the prenatal
      diagnosis of torcular herophili thrombosis. 

PMID- 24277906
TI  - Prenatal sonographic diagnosis of fetus in fetu.

PMID- 24277907
TI  - Sonographic diagnosis of intramural pregnancy.

PMID- 24277908
TI  - Chronic Takayasu arteritis with a multifocal intimal defect and an intimal flap
      in the common carotid artery.

PMID- 24277909
TI  - Detection of early cognitive impairment using AD8 in a young patient with stroke
      with cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy syndrome: a case report.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) syndrome is a hereditary disease resulting from
      NOTCH3 gene mutation. The clinical presentations include migraine, recurrent
      stroke, and cognitive impairment. The severity of cognitive impairment varies in
      different stages, and early recognition poses a challenge. A 47-year-old lady
      presented with chronic migraine and sudden onset of hemiparesis. Magnetic
      resonance imaging revealed compatible findings of CADASIL, which was confirmed by
      mutation analysis of NOTCH3 gene. Early cognitive impairment was detected by her
      score of 3 in Ascertain Dementia 8 (AD8) questionnaire and confirmed by detailed
      neuropsychological assessments. After 21 months of follow-up, deterioration in
      her cognition and ability to perform instrumental activities of daily living were
      significant with a follow-up AD8 score of 7. Ascertain Dementia 8 questionnaire
      is an easy and valid screening tool for early cognitive impairment in patients
      with CADASIL syndrome.

PMID- 24277910
TI  - Cerebrospinal fluid apolipoprotein E concentration and severity of cognitive
      impairment in patients with newly diagnosed Alzheimer's disease.
AB  - BACKGROUND/OBJECTIVE: Apolipoprotein E (apoE) plays an important role in the
      pathogenesis of Alzheimer's disease (AD). Altered cerebrospinal fluid (CSF) and
      plasma levels have been previously reported in patients with AD. We hypothesized
      that CSF apoE levels of patients with newly diagnosed AD might be associated with
      their cognitive performance. METHODS: Patients with AD (N = 71) enrolled into an
      observational study underwent neuropsychological testing (Consortium to Establish
      a Registry for AD [CERAD] plus) at time of diagnosis. The CSF was obtained, and
      apoE concentrations were determined. Generalized linear models were constructed
      to assess the associations of apoE and neuropsychological measures while
      adjusting for important potential confounders. RESULTS: No association of CSF
      apoE levels and cognitive function could be demonstrated. Still, the use of
      neuroleptic drugs, female gender, preprogression time, and lower education were
      linked to worse cognitive function in some domains. CONCLUSION: The CSF apoE
      appears not to be suitable as a biochemical surrogate of cognitive function in AD
      under the given circumstances. By means of longitudinal analyses, potential
      associations with the velocity of decline will be investigated in the near
      future.

PMID- 24277911
TI  - Association between in-hospital mortality and renal dysfunction in 186,219
      patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.
AB  - Using a regional Italian database, we evaluated the relationship between renal
      dysfunction and in-hospital mortality (IHM) in patients with acute stroke
      (ischemic/hemorrhagic). Patients were classified on the basis of renal damage:
      without renal dysfunction, with chronic kidney disease (CKD), and with end-stage
      renal disease (ESRD). Of a total of 186,219 patients with a first episode of
      stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total
      cases) was independently associated with CKD, ESRD, atrial fibrillation (AF),
      age, and Charlson comorbidity index (CCI). In patients with ischemic stroke
      (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI.
      In patients with hemorrhagic stroke (n=32,189), variables that were independently
      associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with
      IHM related to stroke, both ischemic and hemorrhagic, with even higher odds
      ratios than those of other established risk factors, such as age, comorbidities,
      and AF.

PMID- 24277912
TI  - Proprotein convertase subtilisin/kexin type 9: a plausible link between serum
      resistin levels and cardiovascular events.

PMID- 24277914
TI  - Apolipoprotein B/apolipoprotein A-I ratio and apolipoprotein B: long-term
      predictors of myocardial infarction in initially healthy middle-aged men--a 13
      year follow-up.
AB  - We investigated whether serum concentrations of apolipoprotein (apo) B and apoA-I
      and the apoB/apoA-I ratio provided predictive information on myocardial
      infarction (MI) and ischemic stroke during 13 years of follow-up in a group of
      initially clinically healthy 58-year-old men, free from previous cardiovascular
      disease, diabetes, other established disease, or treatment with cardiovascular
      drugs. Multivariate logistic regression analysis showed that the apoB/apoA-I
      ratio and apoB were significant and independent determinants of MI
      (exponentiation of the B coefficient [Exp(beta)] 3.1, 95% confidence interval
      [CI] 1.6-6.3, P=.001, Exp(beta) 2.8, 95% CI 1.1-7.7, P=.045, respectively). The
      area under the receiver-operating characteristics curve as a relative measure of
      test efficiency was highest and significant for both apoB/apoA-I ratio and apoB
      (area under the curve=0.75, P<.001). In conclusion, the apoB/apoA-I ratio and
      apoB are independent risk factors for MI and has the highest efficiencies for
      predicting MI in initially healthy middle-aged men.

PMID- 24277913
TI  - Markers of endothelial dysfunction and evaluation of vascular reactivity tests in
      Behcet disease.
AB  - We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD;
      n=40) and healthy controls (n=20). Serum lipid, homocysteine, asymmetric
      dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels,
      erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated
      dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were
      significantly higher in the BD group (P<.001 for all). Patients with active BD
      had higher serum levels of hsCRP, homocysteine, and ESR compared with those in
      remission (P<.001, P<.001, and P=.005, respectively). Flow-mediated dilatation
      was significantly lower in patients with BD than in controls (P=.001). Flow
      mediated dilatation correlated negatively with BD duration and serum ADMA levels
      (P<.001, r=-.745 and P<.001, r=-.682); a positive correlation was seen between
      serum ADMA levels and BD duration (P<.001, r=.552). Only stepwise multivariate
      regression analysis revealed BD duration to have a significant effect on FMD.
      Flow-mediated dilatation, in conjunction with markers of inflammation, may
      evaluate ED in patients with BD.

PMID- 24277915
TI  - A randomised controlled trial of Silirum vaccine for control of paratuberculosis
      in farmed red deer.
AB  - A randomised controlled trial to assess the efficacy of Silirum vaccine in
      control of paratuberculosis in young farmed deer was carried out in 2008-2009 in
      six New Zealand herds with a history of clinical disease. Vaccination with
      Silirum was carried out in four-month-old deer, and vaccinates (n=1671) and
      controls (n=1664) were weighed at vaccination and at 8 and 12 months old, when
      faecal samples were collected from 125 vaccinates and 123 controls on five farms.
      Deer were slaughtered between 11 and 20 months of age, and the incidence of gross
      visceral lymph node (VLN) pathology typical of paratuberculosis in deer, that is,
      enlarged and/or granulomatous VLN, was recorded. Clinical disease was confirmed
      in 18 controls and seven vaccinates, representing a vaccine efficacy estimate of
      60 per cent (95% CI 3 per cent to 83 per cent, P=0.04). Forty-seven percent (95%
      CI 38 per cent to 56 per cent) of faecal samples from vaccinates and 55 per cent
      (95% CI 46 per cent to 64 per cent) from controls were Mycobacterium avium
      subspecies paratuberculosis positive (P=0.5). Average daily liveweight gain did
      not differ between the cohorts. At slaughter, 1.4 per cent of vaccinates and 4.5
      per cent of controls had VLN pathology, RR=0.32 (95% CI 0.19 to 0.54, P<0.001).
      These data indicate that vaccination with Silirum may be useful as an aid to
      control losses associated with clinical paratuberculosis in young deer. 

PMID- 24277916
TI  - Serovars, bacteriophage types and antimicrobial sensitivities associated with
      salmonellosis in dogs in the UK (1954-2012).
AB  - Serovars and bacteriophage (phage) types were determined for 442 isolates of
      Salmonella enterica from dogs in the UK submitted to the Scottish Salmonella
      Reference Laboratory from 1954 to 2012. The most frequent serovars were
      Salmonella Typhimurium (196 isolates; 44.3 per cent), Dublin (40 isolates; 9.0
      per cent), Enteritidis (28 isolates; 6.3 per cent), Montevideo (19 isolates; 4.3
      per cent), Virchow (10 isolates; 2.3 per cent), Heidelberg (8 isolates; 1.8 per
      cent) and Derby (8 isolates; 1.8 per cent), along with 55 other recognised
      serovars among 127 other isolates, and six incompletely classified isolates.
      Serovars were frequently represented by strains commonly associated with poultry,
      cattle or pigs and their products. Among 196 Salmonella Typhimurium isolates from
      dogs, the most frequent phage types (definitive types) were the multiple
      antimicrobial-resistant strains DT104 (62 isolates), DT204c (18 isolates) and
      DT193 (8 isolates), along with antimicrobial sensitive wild finch strains DT40
      (13 isolates) and DT56 variant (8 isolates). Eleven of 28 isolates of Salmonella
      Enteritidis were phage type 4. S enterica was frequently recovered from faecal or
      intestinal samples of dogs with diarrhoea, although many dogs had concurrent
      infection with other enteric pathogens. Salmonella Dublin was recovered from the
      brain and/or cerebrospinal fluid of two dogs with meningoencephalitis. Salmonella
      Kedougou was isolated from the joint fluid of a dog with septic arthritis.
      Salmonella Typhimurium and Salmonella Dublin were each recovered from the vaginas
      of bitches that had aborted. Isolates of Salmonella Enteritidis phage types 1, 4
      and 8, Salmonella Typhimurium DT104, Salmonella Dublin and Salmonella Indiana
      were isolated from clinically healthy dogs in households where the same strains
      were recovered from human beings with diarrhoea. The pattern ampicillin
      chloramphenicol-spectinomycin-streptomycin-sulfamethoxazole-tetracycline
      (ACSpSSuT) was the most frequent resistance phenotype and was observed in 44
      (13.3 per cent) of 330 isolates. Dogs in the UK are exposed to a wide variety of
      serovars of S enterica, sometimes associated with clinical disease, and represent
      a zoonotic risk.

PMID- 24277917
TI  - Isolation of Leptospires from genital tract of sheep.

PMID- 24277918
TI  - Cricothyrotomy: possible first-choice emergency airway access for treatment of
      acute upper airway obstruction in dogs and cats.

PMID- 24277919
TI  - Assessment of seroconversion to a peste des petits ruminants virus live vaccine
      in Arabian oryx (Oryx leucoryx).

PMID- 24277920
TI  - Lead intoxication incidents associated with shot from clay pigeon shooting.

PMID- 24277922
TI  - Military wound ballistics: history and renaissance.

PMID- 24277923
TI  - Challenges of managing snakebite envenomation in a deployed setting.
AB  - Snake bite envenomation causes a significant health burden globally, especially
      in austere or resource poor settings. This case series describes envenomation in
      two adults and two children presenting to the Role 3 Medical Treatment Facility
      in Camp Bastion, Afghanistan. Each case has similarities with respect to the
      coagulopathy of envenomation but differs in terms of time delay to presentation
      and response to treatment, including reactions to antivenom. We discuss the
      challenges and ethical dilemmas in delayed-presentation snakebite, the diagnosis
      and treatment of coagulopathy and the role of antivenom and surgical debridement.

PMID- 24277924
TI  - Pneumoperitoneum without visceral trauma: an under-recognised phenomenon after
      blast injury?
AB  - OBJECTIVES: The management of patients who have sustained blast injuries poses an
      important challenge for military healthcare professionals. Current military
      operations are generating large numbers of casualties and modern military
      healthcare facilities are increasingly using CT scanning to facilitate their
      management. This small case series serves to draw attention to a rare (or
      possibly under-reported) phenomenon after blast injury. METHODS AND RESULTS: We
      report two patients exposed to blast who had pneumoperitoneum identified by CT
      scan but who did not have abdominal visceral injury or ballistic peritoneal
      violation. DISCUSSION: The use of cross-sectional imaging is leading to the
      recognition of otherwise occult injury. Military practitioners should be aware of
      this injury pattern when using CT to help select patients for conservative
      management after abdominal blast injury.

PMID- 24277925
TI  - Children's catching performance when the demands on the postural system is
      altered.
AB  - In many dynamic interceptive actions performers need to integrate activity of
      manual and postural subsystems for successful performance. Groups of different
      skill level (poor and good catchers), (mean age = 9.1 and 9.4 respectively) were
      required to perform one-handed catches under different postural constraints:
      standing; standing in contact with a postural support aid by their side (PSAS) or
      to the left of their trunk (PSAF); Tandem; and sitting (control). Results
      revealed that, for poor catchers, the number of successful catches increased and
      grasp errors decreased significantly when sitting and with both postural aids in
      comparison with standing alone and Tandem conditions. Kinematic analyses showed
      that the postural aid devices reduced head sway in the anterior-posterior
      direction, while the PSAF reduced lateral head sway. The poor catchers'
      performance benefited from an enlarged support surface, and reduction of lateral
      sway. Good catchers performed successfully under all task constraints, signifying
      the existence of a functional relationship between postural and grasping
      subsystems during performance. The results are discussed in the frame of
      Bernstein's (1967) and Newell's (1986) theory. 

PMID- 24277926
TI  - Assessing physical activity during youth sport: the Observational System for
      Recording Activity in Children: Youth Sports.
AB  - The purpose of this study was to evaluate the validity and interrater reliability
      of the Observational System for Recording Activity in Children: Youth Sports
      (OSRAC:YS). Children (N = 29) participating in a parks and recreation soccer
      program were observed during regularly scheduled practices. Physical activity
      (PA) intensity and contextual factors were recorded by momentary time-sampling
      procedures (10-second observe, 20-second record). Two observers simultaneously
      observed and recorded children's PA intensity, practice context, social context,
      coach behavior, and coach proximity. Interrater reliability was based on
      agreement (Kappa) between the observer's coding for each category, and the
      Intraclass Correlation Coefficient (ICC) for percent of time spent in MVPA.
      Validity was assessed by calculating the correlation between OSRAC:YS estimated
      and objectively measured MVPA. Kappa statistics for each category demonstrated
      substantial to almost perfect interobserver agreement (Kappa = 0.67-0.93). The
      ICC for percent time in MVPA was 0.76 (95% C.I. = 0.49-0.90). A significant
      correlation (r = .73) was observed for MVPA recorded by observation and MVPA
      measured via accelerometry. The results indicate the OSRAC:YS is a reliable and
      valid tool for measuring children's PA and contextual factors during a youth
      soccer practice. 

PMID- 24277928
TI  - Application of Stable Isotope Tracers in the Study of Exercise Metabolism in
      Children: A Primer.
AB  - Exercise metabolism in children has traditionally been assessed using the
      respiratory exchange ratio (RER) to determine the contributions of fat and
      carbohydrate to the exercise energy demands. Although easily measured, RER
      measurements have limitations. Other methods to assess metabolism such as the
      obtainment of a muscle biopsy and the use of nuclear magnetic resonance
      spectroscopy carry ethical and feasibility concerns, respectively, which limit
      their use in studies involving children. Stable isotopes, used routinely in
      studies involving adults, can also be applied in studies involving children in an
      ethical and feasible manner. Two common stable isotopes used in metabolic studies
      involving children include carbon-13 (C) and nitrogen-15 (N). C-glucose can be
      used to study carbohydrate metabolism and N-glycine can be used to assess protein
      metabolism. This article reviews the use of C-glucose and N-glycine to study
      exercise metabolism in children, considers some of the associated ethical
      aspects, explains the general methodology involved in administering these
      isotopes and the resources required, and describes studies involving children
      utilizing these methods. Finally, suggestions for future research are provided to
      encourage further use of these techniques.

PMID- 24277927
TI  - Caffeine supplementation and reactive agility in elite youth soccer players.
AB  - This study examined the effects of caffeine supplementation (6 mg.kg-1) on
      performance of a reactive agility test (RAT) in 17 elite, male, youth (M = 14 y)
      soccer players. Using a double-blind, repeated-measures design, players completed
      4 days of testing on the RAT after a standardized warm-up. On day 1,
      anthropometric measurements were taken and players were accommodated to the RAT.
      On day 2, baseline performance was established. Caffeine or placebo conditions
      were randomly assigned on day 3 and the condition was reversed on day 4. Players
      completed 3 randomized trials of the RAT on days 2, 3, and 4 with at least 1
      trial to the players' dominant and nondominant sides. There were no significant
      differences among conditions in reaction time (RT) to the dominant side, heart
      rates at any point of measurement, or ratings of perceived exertion (RPE) after
      completion of the warm-up. Caffeine produced faster RT to the nondominant side (P
      = .041) and higher RPE at the conclusion of the RAT (P = .013). The effect on the
      total time (TT) to complete the agility test to the nondominant side approached
      significance (P = .051). Sprint time and TT to either side did not differ.
      Caffeine supplementation may provide ergogenic benefit to elite, male, youth
      soccer players. 

PMID- 24277929
TI  - Cholesterol sulfate and cholesterol sulfotransferase inhibit gluconeogenesis by
      targeting hepatocyte nuclear factor 4alpha.
AB  - Sulfotransferase (SULT)-mediated sulfation represents a critical mechanism in
      regulating the chemical and functional homeostasis of endogenous and exogenous
      molecules. The cholesterol sulfotransferase SULT2B1b catalyzes the
      sulfoconjugation of cholesterol to synthesize cholesterol sulfate (CS). In this
      study, we showed that the expression of SULT2B1b in the liver was induced in
      obese mice and during the transition from the fasted to the fed state, suggesting
      that the regulation of SULT2B1b is physiologically relevant. CS and SULT2B1b
      inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte
      nuclear factor 4alpha (HNF4alpha) in both cell cultures and transgenic mice.
      Treatment of mice with CS or transgenic overexpression of the CS-generating
      enzyme SULT2B1b in the liver inhibited hepatic gluconeogenesis and alleviated
      metabolic abnormalities both in mice with diet-induced obesity (DIO) and in
      leptin-deficient (ob/ob) mice. Mechanistically, CS and SULT2B1b inhibited
      gluconeogenesis by suppressing the expression of acetyl coenzyme A (acetyl-CoA)
      synthetase (Acss), leading to decreased acetylation and nuclear exclusion of
      HNF4alpha. Our results also suggested that leptin is a potential effector of
      SULT2B1b in improving metabolic function. We conclude that SULT2B1b and its
      enzymatic by-product CS are important metabolic regulators that control glucose
      metabolism, suggesting CS as a potential therapeutic agent and SULT2B1b as a
      potential therapeutic target for metabolic disorders. 

PMID- 24277930
TI  - A p21-ZEB1 complex inhibits epithelial-mesenchymal transition through the
      microRNA 183-96-182 cluster.
AB  - The tumor suppressor p21 acts as a cell cycle inhibitor and has also been shown
      to regulate gene expression by functioning as a transcription corepressor. Here,
      we identified p21-regulated microRNAs (miRNAs) by sequencing small RNAs from
      isogenic p21(+/+) and p21(-/-) cells. Three abundant miRNA clusters, miR-200b
      200a-429, miR-200c-141, and miR-183-96-182, were downregulated in p21-deficient
      cells. Consistent with the known function of the miR-200 family and p21 in
      inhibition of the epithelial-mesenchymal transition (EMT), we observed EMT upon
      loss of p21 in multiple model systems. To explore a role of the miR-183-96-182
      cluster in EMT, we identified its genome-wide targets and found that miR-183 and
      miR-96 repressed common targets, including SLUG, ZEB1, ITGB1, and KLF4.
      Reintroduction of miR-200, miR-183, or miR-96 in p21(-/-) cells inhibited EMT,
      cell migration, and invasion. Conversely, antagonizing miR-200 and miR-183-96-182
      cluster miRNAs in p21(+/+) cells increased invasion and elevated the levels of
      VIM, ZEB1, and SLUG mRNAs. Furthermore, we found that p21 forms a complex with
      ZEB1 at the miR-183-96-182 cluster promoter to inhibit transcriptional repression
      of this cluster by ZEB1, suggesting a reciprocal feedback loop. 

PMID- 24277931
TI  - Transcription factor Ets1, but not the closely related factor Ets2, inhibits
      antibody-secreting cell differentiation.
AB  - B cell differentiation into antibody-secreting cells (ASCs) is a tightly
      regulated process under the control of multiple transcription factors. One such
      transcription factor, Ets1, blocks the transition of B cells to ASCs via two
      separate activities: (i) stimulating the expression of target genes that promote
      B cell identity and (ii) interfering with the functional activity of the
      transcription factor Blimp1. Ets1 is a member of a multigene family, several
      members of which are expressed within the B cell lineage, including the closely
      related protein Ets2. In this report, we demonstrate that Ets1, but not Ets2, can
      block ASC formation despite the fact that Ets1 and Ets2 bind to apparently
      identical DNA sequence motifs and are thought to regulate overlapping sets of
      target genes. The DNA binding domain of Ets1 is required, but not sufficient by
      itself, to block ASC formation. In addition, less conserved regions within the N
      terminus of Ets1 play an important role in inhibiting B cell differentiation.
      Differences between the N termini of Ets1 and Ets2, rather than differences in
      the DNA binding domains, determine whether the proteins are capable of blocking
      ASC formation or not. 

PMID- 24277932
TI  - Ethanol-induced upregulation of 10-formyltetrahydrofolate dehydrogenase helps
      relieve ethanol-induced oxidative stress.
AB  - Alcoholism induces folate deficiency and increases the risk for embryonic
      anomalies. However, the interplay between ethanol exposure and embryonic folate
      status remains unclear. To investigate how ethanol exposure affects embryonic
      folate status and one-carbon homeostasis, we incubated zebrafish embryos in
      ethanol and analyzed embryonic folate content and folate enzyme expression.
      Exposure to 2% ethanol did not change embryonic total folate content but
      increased the tetrahydrofolate level approximately 1.5-fold. The expression of 10
      formyltetrahydrofolate dehydrogenase (FDH), a potential intracellular
      tetrahydrofolate reservoir, was increased in both mRNA and protein levels.
      Overexpressing recombinant FDH in embryos alleviated the ethanol-induced
      oxidative stress in ethanol-exposed embryos. Further characterization of the
      zebrafish fdh promoter revealed that the -124/+40 promoter fragment was the
      minimal region required for transactivational activity. The results of site
      directed mutagenesis and binding analysis revealed that Sp1 is involved in the
      basal level of expression of fdh but not in ethanol-induced upregulation of fdh.
      On the other hand, CEBPalpha was the protein that mediated the ethanol-induced
      upregulation of fdh, with an approximately 40-fold increase of fdh promoter
      activity when overexpressed in vitro. We concluded that upregulation of fdh
      involving CEBPalpha helps relieve embryonic oxidative stress induced by ethanol
      exposure. 

PMID- 24277933
TI  - Psy2 targets the PP4 family phosphatase Pph3 to dephosphorylate Mth1 and repress
      glucose transporter gene expression.
AB  - The reversible nature of protein phosphorylation dictates that any protein kinase
      activity must be counteracted by protein phosphatase activity. How phosphatases
      target specific phosphoprotein substrates and reverse the action of kinases,
      however, is poorly understood in a biological context. We address this question
      by elucidating a novel function of the conserved PP4 family phosphatase Pph3
      Psy2, the yeast counterpart of the mammalian PP4c-R3 complex, in the glucose
      signaling pathway. Our studies show that Pph3-Psy2 specifically targets the
      glucose signal transducer protein Mth1 via direct binding of the EVH1 domain of
      the Psy2 regulatory subunit to the polyproline motif of Mth1. This activity is
      required for the timely dephosphorylation of the downstream transcriptional
      repressor Rgt1 upon glucose withdrawal, a critical event in the repression of HXT
      genes, which encode glucose transporters. Pph3-Psy2 dephosphorylates Mth1, an
      Rgt1 associated corepressor, but does not dephosphorylate Rgt1 at sites
      associated with inactivation, in vitro. We show that Pph3-Psy2 phosphatase
      antagonizes Mth1 phosphorylation by protein kinase A (PKA), the major protein
      kinase activated in response to glucose, in vitro and regulates Mth1 function via
      putative PKA phosphorylation sites in vivo. We conclude that the Pph3-Psy2
      phosphatase modulates Mth1 activity to facilitate precise regulation of HXT gene
      expression by glucose. 

PMID- 24277934
TI  - In vivo interaction proteomics reveal a novel p38 mitogen-activated protein
      kinase/Rack1 pathway regulating proteostasis in Drosophila muscle.
AB  - Several recent studies suggest that systemic aging in metazoans is differentially
      affected by functional decline in specific tissues, such as skeletal muscle. In
      Drosophila, longevity appears to be tightly linked to myoproteostasis, and the
      formation of misfolded protein aggregates is a hallmark of senescence in aging
      muscle. Similarly, defective myoproteostasis is described as an important
      contributor to the pathology of several age-related degenerative muscle diseases
      in humans, e.g., inclusion body myositis. p38 mitogen-activated protein kinase
      (MAPK) plays a central role in a conserved signaling pathway activated by a
      variety of stressful stimuli. Aging p38 MAPK mutant flies display accelerated
      motor function decline, concomitant with an enhanced accumulation of detergent
      insoluble protein aggregates in thoracic muscles. Chemical genetic experiments
      suggest that p38-mediated regulation of myoproteostasis is not limited to the
      control of reactive oxygen species production or the protein degradation pathways
      but also involves upstream turnover pathways, e.g., translation. Using affinity
      purification and mass spectrometry, we identified Rack1 as a novel substrate of
      p38 MAPK in aging muscle and showed that the genetic interaction between p38b and
      Rack1 controls muscle aggregate formation, locomotor function, and longevity.
      Biochemical analyses of Rack1 in aging and stressed muscle suggest a model
      whereby p38 MAPK signaling causes a redistribution of Rack1 between a ribosome
      bound pool and a putative translational repressor complex. 

PMID- 24277935
TI  - FACT and the H2B N tail.
AB  - The FACT histone chaperone/nucleosome reorganization factor plays key roles in
      nucleosome dynamics during transcription. A new study has linked a specific
      domain in the H2B N terminus to the activity of FACT in regulating nucleosome
      disassembly at promoters during transcription activation and nucleosome
      reassembly at coding regions during transcription elongation. 

PMID- 24277936
TI  - Mammary-specific gene activation is defined by progressive recruitment of STAT5
      during pregnancy and the establishment of H3K4me3 marks.
AB  - Differentiation of mammary secretory epithelium during pregnancy is characterized
      by sequential activation of genes over several orders of magnitude. Although the
      transcription factor STAT5 is key to alveolar development, it is not clear to
      what extent it controls temporal activation of genetic programs in secretory
      epithelium. To uncover molecular mechanisms effecting progressive
      differentiation, we explored genome-wide STAT5 binding and H3K4me3 (i.e.,
      trimethylated histone H3 at K4) marks in mammary tissues at early and
      midpregnancy and at parturition. STAT5 binding to genes induced during pregnancy
      was low in immature mammary tissue but increased with epithelial differentiation.
      Increased STAT5 binding was associated with the establishment of H3K4me3 marks
      and transcriptional activation. STAT5 binding preceded the formation of H3K4me3
      marks in some mammary-specific genes. De novo STAT5 binding was also found at
      distal sites, indicating enhancers. Furthermore, we established an exhaustive
      mammary transcriptome. Through integration of RNA-seq and STAT5 and H3K4me4 ChIP
      seq data, we discovered novel mammary-specific alternative promoters and genes,
      including noncoding RNAs. Our findings suggest that STAT5 is an early step in
      establishing transcription complexes on genes specifically expressed in mammary
      epithelium. This is the first study in an organ that links progressive chromatin
      occupancy of STAT5 to the acquisition of H3K4me3 marks and transcription during
      hormone-induced differentiation. 

PMID- 24277937
TI  - Mapping the protein interaction network for TFIIB-related factor Brf1 in the RNA
      polymerase III preinitiation complex.
AB  - TFIIB-related factor Brf1 is essential for RNA polymerase (Pol) III recruitment
      and open-promoter formation in transcription initiation. We site specifically
      incorporated a nonnatural amino acid cross-linker into Brf1 to map its protein
      interaction targets in the preinitiation complex (PIC). Our cross-linking
      analysis in the N-terminal domain of Brf1 indicated a pattern of multiple protein
      interactions reminiscent of TFIIB in the Pol active-site cleft. In addition to
      the TFIIB-like protein interactions, the Brf1 cyclin repeat subdomain is in
      contact with the Pol III-specific C34 subunit. With site-directed hydroxyl
      radical probing, we further revealed the binding between Brf1 cyclin repeats and
      the highly conserved region connecting C34 winged-helix domains 2 and 3. In
      contrast to the N-terminal domain of Brf1, the C-terminal domain contains
      extensive binding sites for TBP and Bdp1 to hold together the TFIIIB complex on
      the promoter. Overall, the domain architecture of the PIC derived from our cross
      linking data explains how individual structural subdomains of Brf1 integrate the
      protein network from the Pol III active center to the promoter for transcription
      initiation. 

PMID- 24277938
TI  - S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling
      pathway.
AB  - Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a key
      regulator in the signals transduced by proinflammatory cytokines and Toll-like
      receptors (TLRs). The regulatory mechanism of TAK1 in response to various tissue
      types and stimuli remains incompletely understood. Here, we show that ribosomal
      S6 kinase 1 (S6K1) negatively regulates TLR-mediated signals by inhibiting TAK1
      activity. S6K1 overexpression causes a marked reduction in NF-kappaB and AP-1
      activity induced by stimulation of TLR2 or TLR4. In contrast, S6K1(-/-) and S6K1
      knockdown cells display enhanced production of inflammatory cytokines. Moreover,
      S6K1(-/-) mice exhibit decreased survival in response to challenge with
      lipopolysaccharide (LPS). We found that S6K1 inhibits TAK1 kinase activity by
      interfering with the interaction between TAK1 and TAB1, which is a key regulator
      protein for TAK1 catalytic function. Upon stimulation with TLR ligands, S6K1
      deficiency causes a marked increase in TAK1 kinase activity that in turn induces
      a substantial enhancement of NF-kappaB-dependent gene expression, indicating that
      S6K1 is negatively involved in the TLR signaling pathway by the inhibition of
      TAK1 activity. Our findings contribute to understanding the molecular
      pathogenesis of the impaired immune responses seen in type 2 diabetes, where S6K1
      plays a key role both in driving insulin resistance and modulating TLR signaling.

PMID- 24277940
TI  - Post-translational modifications: a major focus for the future of proteomics.

PMID- 24277939
TI  - The primitive endoderm segregates from the epiblast in beta1 integrin-deficient
      early mouse embryos.
AB  - We analyzed the mechanism of developmental failure in implanted beta1 integrin
      null blastocysts and found that primitive endoderm cells are present but
      segregate away from, instead of forming an epithelial layer covering, the inner
      cell mass. This cell segregation phenotype was also reproduced in beta1 integrin
      null embryoid bodies, in which primitive endoderm cells segregated and appeared
      as miniature aggregates detached from the core spheroids, and a primitive
      endoderm layer failed to form on the surface. Restricted beta1 integrin gene
      deletion in embryos using Ttr-Cre or Sox2-Cre indicated that the loss of integrin
      function in the cells of the inner core rather than the outer layer is
      responsible for the failure to form a primitive endoderm layer. We conclude that
      beta1 integrin is essential for the attachment of the primitive endoderm layer to
      the epiblast during the formation of a basement membrane, a process concurrent
      with the transition from cadherin- to integrin-mediated cell adhesion. 

PMID- 24277941
TI  - Should we perform kidney transplants on foreign nationals?
AB  - In Canada, there are currently no guidelines at either the federal or provincial
      level regarding the provision of kidney transplantation services to foreign
      nationals (FN). Renal transplant centres have, in the past, agreed to put refugee
      claimants and other FNs on the renal transplant waiting list, in part, because
      these patients (refugee claimants) had health insurance through the Interim
      Federal Health Programme to cover the costs of medication and hospital care.
      However, severe cuts recently made to this programme have forced clinicians to
      question whether they should continue with transplants for FNs, for financial and
      ethical reasons. This paper first examines different national policies (eg, in
      Canada, USA, France and the UK) to map the diversity of approaches regarding
      transplantation for FNs, and then works through different considerations commonly
      used to support or oppose the provision of organs to these patients: (1) the
      organ shortage; (2) the free-rider problem; (3) the risk of becoming a transplant
      destination; (4) the impact on organ donation rates; (5) physicians' duties; (6)
      economic concerns; (7) vulnerability. Using a Canadian case as a focus, and
      generalising through a review of various national policies, we analyse the
      arguments for and against transplantation for FNs with a view to bringing clarity
      to what is a sensitive political and clinical management issue. Our aim is to
      help transplant centres, clinicians and ethicists reflect on the merits of
      possible options, and the rationales behind them. 

PMID- 24277954
TI  - Magnetic Particle Imaging - from particle science to imaging technology.

PMID- 24277955
TI  - Numerically efficient estimation of relaxation effects in magnetic particle
      imaging.
AB  - Current simulations of the signal in magnetic particle imaging (MPI) are either
      based on the Langevin function or on directly measuring the system function. The
      former completely ignores the influence of finite relaxation times of magnetic
      particles, and the latter requires time-consuming reference scans with an
      existing MPI scanner. Therefore, the resulting system function only applies for a
      given tracer type and the properties of the applied scanning trajectory. It
      requires separate reference scans for different trajectories and does not allow
      simulating theoretical magnetic particle suspensions. The most accessible and
      accurate way for including relaxation effects in the signal simulation would be
      using the Langevin equation. However, this is a very time-consuming approach
      because it calculates the stochastic dynamics of the individual particles and
      averages over large particle ensembles. In the current article, a numerically
      efficient way for approximating the averaged Langevin equation is proposed, which
      is much faster than the approach based on the Langevin equation because it is
      directly calculating the averaged time evolution of the magnetization. The
      proposed simulation yields promising results. Except for the case of small
      orthogonal offset fields, a high agreement with the full but significantly slower
      simulation could be shown.

PMID- 24277956
TI  - Bioavailability of heavy metals using in vitro digestion model: a state of
      present knowledge.
AB  - In vitro digestion models are currently being used to detect heavy metals in
      soil, foods, consumer products, and house dust. However, determining the
      bioavailability of heavy metals using such models has limited applications
      compared with total heavy metal determination. This paper provides an overview of
      current trends in the development and utilization of in vitro digestion models
      for soil, foods, consumer products and house dust, as well as information that
      can be used to develop in vitro digestion models. We found that these models are
      applied more on food samples than on other samples, and that in vitro digestion
      models can be used in exposure and health risk assessments, which help determine
      cancer and non-cancer risks. Thus, this review improves our understanding and
      provides suggestions for a health risk assessment application using in vitro
      digestion model outputs.

PMID- 24277957
TI  - Effects of blood lead level on biochemical and hematological parameters in
      children with neurological diseases of Western Maharashtra, India.
AB  - BACKGROUND: Lead is found in small but appreciable quantities in air, soil,
      drinking water, and food. Exposure to such amounts of lead does not lead to acute
      lead toxicity but produces subtle effects particularly in children. The aim of
      this study was to investigate the effects of blood lead level on biochemical and
      hematological parameters in children with neurological diseases in Western
      Maharashtra, India, and to estimate the blood lead level by liver and kidney
      function tests and hematological parameters in children with neurological
      disorders admitted to the pediatric ward and compare them with healthy controls.
      METHODS: In this study, 30 children with various neurological disorders admitted
      to the pediatric ward of Smt. Kashibai Navale Medical College and General
      Hospital, Pune, Maharashtra, India, were compared with 30 age- and sex-matched
      healthy controls. Four milliliters of venous blood was collected for estimation
      of blood lead level, and biochemical and hematological parameters were determined
      using standard methods. RESULTS: Blood lead level was significantly increased in
      the study group (p<0.01, 65.38%) compared to that in the control group. When
      different neurological conditions were grouped into three groups according to
      blood lead levels, there was a significant difference between the groups. All
      other biochemical and hematological parameters were not significantly altered in
      the study group as compared to the control group. CONCLUSIONS: Neurologically
      challenged children are more vulnerable to lead intoxication. It is imperative
      for the parents to take extra care of their children's food habits and limit hand
      to-mouth activities to prevent lead intoxication.

PMID- 24277958
TI  - Bone turnover markers, osteoprotegerin and RANKL cytokines in children with
      cystic fibrosis.
AB  - PURPOSE: Some scientific studies show decreased bone mineral density and
      increased fracture frequency in adult patients with cystic fibrosis (CF). The
      mechanism for early bone loss in CF patients are multifactorial: chronic
      pulmonary inflammation, malnutrition, reduced physical activity, delayed pubertal
      maturation. The aim of this study was to assess bone metabolism markers with
      special attention paid to osteoprotegerin (OPG) and receptor activator of nuclear
      factor kappaB ligand (RANKL) balance in CF children. MATERIAL AND METHODS: The
      study included 35 children with diagnosed CF and 35 healthy controls aged 5-9
      years (median 7.0 years). Serum levels of fat soluble vitamins were measured by
      chemiluminescence (vitamin D) and HPLC (vitamins A, E) methods. Concentrations of
      bone metabolism markers were determined by immunoenzymatic assay. RESULTS: Mean
      levels of fat soluble vitamins (A, D, E) were lower in patients with CF compared
      to controls. In CF children we observed a significant (p<0.01) decrease in
      concentration of bone formation marker (osteocalcin) and similar bone resorption
      markers (CTX, TRACP5b) in comparison with healthy children. The serum level of
      OPG was significantly lower (p<0.05) and RANKL nearly 2-fold higher in patients
      with CF than in the healthy ones. The ratio of OPG to RANKL was about 2-fold
      lower in children with CF compared to healthy peers (p<0.01). CONCLUSION: In CF
      children, an imbalance between bone formation and resorption processes occurs. An
      increase serum RANKL concentration coexisting with lower levels of OPG may be
      associated with intensification of bone resorption.

PMID- 24277959
TI  - The dynamics of soluble Fas/APO 1 apoptotic biochemical marker in acute ischemic
      stroke patients.
AB  - PURPOSE: Until recently, neuronal death in ischemic stroke infarction was
      ascribed exclusively to necrotic process. However, experimental animal models of
      cerebral ischemia suggest apoptosis to play a role in the pathogenesis of
      cerebral infarction. The aim of this study was to determine the level and monitor
      the dynamics of soluble Fas/APO 1 (sFas/APO 1) in serum and cerebrospinal fluid
      of acute ischemic stroke patients. MATERIAL AND METHODS: This prospective study
      included 23 patients with first ever, computed tomography verified acute ischemic
      stroke and 20 control subjects with other functional neurologic disorders. Serum
      and cerebrospinal fluid sFas/APO 1 levels were determined on several occasions.
      Blood samples were obtained on day 1, 3 and 12, and lumbar puncture on day 3 and
      12 of disease onset. Quantitative sandwich ELISA method was used on sFas/APO 1
      determination. RESULTS: On day 1 of disease onset, serum and cerebrospinal fluid
      sFas/APO 1 levels were significantly higher in stroke patients as compared to
      control subjects, and then gradually declined during the period of monitoring.
      CONCLUSION: Study results confirmed the dynamic pattern of sFas/APO 1 in serum
      and cerebrospinal fluid of patients with acute ischemic stroke, suggesting the
      possible role of apoptosis in the pathogenesis of cerebral infarction.

PMID- 24277960
TI  - Prevalence of rotavirus diarrhea among hospitalized under-five children.
AB  - OBJECTIVE: To estimate the prevalence of rotavirus diarrhea among hospitalized
      children less than 5 years of age in Kerala State and to determine the
      circulating strains of rotavirus in Kerala. DESIGN: Multicenter, cross-sectional
      study. SETTING: Eight representative hospitals in Kunnathunadu Thaluk, Ernakulam
      district, Kerala. PARTICIPANTS: Children in the age group under 5 years. METHODS:
      Hospitalized children admitted with acute diarrhea were examined and standardized
      case report form was used to collect demographic, clinical and health outcome.
      Stool specimens were collected and ELISA testing was done. ELISA rotavirus
      positive samples were tested by reverse transcription PCR for G and P typing (CMC
      Vellore). RESULTS: Among the 1827 children, 648 (35.9%) were positive for
      rotavirus by the Rotaclone ELISA test. The prevalence of rotavirus diarrhea in
      infants less than 6 months of age was 24.7%; 6- 11 months 31.9%; 12- 23 months
      41.9%; 24- 35 months 46.9%; and 33.3% in 36- 59 months. Rotavirus infections were
      most common during the dry months from January through May. G1P[8] (49.7%) was
      the most common strain identified followed by G9P[8] (26.4%), G2P[4] (5.5%),
      G9P[4] (2.6%) and G12P[6] (1.3%). CONCLUSIONS: The prevalence of rotavirus
      diarrhea among hospitalized children less than 5 years is high in Ernakulam
      district, Kerala State.

PMID- 24277961
TI  - Intranasal clonidine vs. midazolam as premedication in children: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare anxiolysis produced by intranasal clonidine with intranasal
      midazolam as premedication in children undergoing surgery. DESIGN: Double-blind
      randomized controlled study. SETTING: Tertiary-care hospital, July 2009 to June
      2010. PATIENTS: 60 American Society of Anesthesiologists physical status I-II
      surgical patients aged 1-10 yr. INTERVENTION: Participants randomly allocated to
      receive either intranasal clonidine 4 mcg/kg (Group I) with atropine or
      intranasal midazolam 0.3 mg/kg (Group II). OUTCOME MEASURES: Primary:
      satisfactory anxiolysis at 30 min after drug administration. Secondary:
      satisfactory mask acceptance, times of onset of sedation and anxiolysis, drug
      acceptance, level of sedation, wake-up score and side effects. RESULTS: All
      children achieved satisfactory anxiolysis at 30 min. Group I fared significantly
      better than GroupII on mask acceptance (100% in Group I vs. 80% in Group II;
      P=0.024), drug acceptance (93% vs. 13%; P<0.001) and proportion of patients with
      satisfactory wake up scores (100% vs. 53%; P<0.001). Group II patients had
      significantly faster onset of sedation (median 10 min vs. 15 min; P<0.05) but not
      that of anxiolysis compared to Group-I (median 10 min for both groups; P>0.05).
      Side effects were significantly more frequent in Group II. CONCLUSIONS: Though
      intranasal midazolam produced faster sedation, both the drugs produced
      satisfactory anxiolysis at 30 min.

PMID- 24277962
TI  - Cord blood thyroid stimulating hormone level--interpretation in light of
      perinatal factors.
AB  - OBJECTIVE: To study the influence of perinatal factors on cord blood TSH (CB TSH)
      levels. DESIGN: Cross-sectional study. SETTING: Tertiary care private hospital.
      METHODS: CB TSH levels were measured in 952 live-born infants using
      electrochemiluminescence immunoassay. The effect of perinatal factors on the CB
      TSH levels was analyzed statistically. RESULTS: The median CB TSH was 8.75
      microIU/mL (IQR = 6.475 -12.82) with 11.5% neonates having values more than 20.
      CB TSH was significantly raised in first order neonates (P <0.01) and in babies
      delivered by assisted vaginal delivery and normal delivery (P <0.01). Neonates
      who had fetal distress or non-progress of labour had significantly higher CB TSH
      than those who were delivered by elective caesarean section. Requirement of
      resuscitation beyond the initial steps and low Apgar scores at 1 minute also
      resulted in significantly raised CB TSH (both P <0.01). Maternal hypothyroidism,
      maternal hypertension and neonates weight appropriateness for gestation,
      gestational age and birth weight did not have significant effect. CONCLUSIONS:
      The incidence of high cord blood TSH (>20 microU/mL) is 11.45%. On multivariate
      analysis, requirement of resuscitation, mode of delivery and fetal distress as
      indication for LSCS were significant factors affecting CB TSH values. Hence,
      these values need to be interpreted in light of perinatal factors.

PMID- 24277963
TI  - Fractional exhaled nitric oxide in children with acute exacerbation of asthma.
AB  - OBJECTIVE: To determine whether fractional exhaled nitric oxide (FENO) has a
      utility as a diagnostic or predictive maker in acute exacerbations of asthma in
      children. DESIGN: Analysis of data collected in a pediatric asthma cohort.
      SETTING: Pediatric Chest Clinic of a tertiary care hospital. METHODS: A cohort of
      children with asthma was followed up every 3 months in addition to any acute
      exacerbation visits. Pulmonary function tests (PFT) and FENO were obtained at all
      visits. We compared the FENO values during acute exacerbations with those at
      baseline and those during the follow up. RESULTS: 243 asthmatic children were
      enrolled from August 2009 to December 2011 [mean (SD) follow up - 434 (227)
      days]. FENO during acute exacerbations was not different from FENO during follow
      up; however, FENO was significantly higher than personal best FENO during follow
      up (P < 0.0001). FENO during acute exacerbation did not correlate with the
      severity of acute exacerbation (P=0.29). The receiver operating characteristics
      curve for FENO as a marker for acute exacerbation had an area under the curve of
      0.59. Cut-off of 20 ppb had a poor sensitivity (44%) and specificity (68.7%) for
      acute exacerbation. CONCLUSIONS: FENO levels during acute exacerbation increase
      from their personal best levels. However, no particular cut off could be
      identified that could help in either diagnosing acute exacerbation or predicting
      its severity.

PMID- 24277964
TI  - Management of children with severe acute malnutrition: experience of Nutrition
      Rehabilitation Centers in Uttar Pradesh, India.
AB  - OBJECTIVE: To assess the effectiveness of facility-based care for children with
      severe acute malnutrition (SAM) in Nutrition Rehabilitation Centers (NRC).
      DESIGN: Review of data. SETTING: 12 NRCs in Uttar Pradesh, India. PARTICIPANTS:
      Children admitted to NRCs (Jan 1, 2010 - Dec 31, 2011). INTERVENTION: Detection
      and treatment of SAM with locally-adapted protocols. OUTCOMES: Survival, default,
      discharge, and recovery rates. RESULTS: 54.6% of the total 1,229 children
      admitted were boys, 81.6% were in the age group 6-23 months old, 86% belonged to
      scheduled tribes, scheduled castes, or other backward castes, and 42% had edema
      or medical complications. Of the 1,181 program exits, 14 (1.2%) children died,
      657 (47.2%) children defaulted, and 610 (51.7%) children were discharged The
      average (SD) weight gain was 12.1 (7.3)g/kg body weight/day and the average (SD)
      length of stay was 13.2 (5.6) days. 206 (46.8%) children were discharged after
      recovery (weight gain >15%) while 324 (53.2%) were discharged, non-recovered
      (weight gain <15%). CONCLUSIONS: NRCs provide life-saving care for children with
      SAM; however, the protocols and therapeutic foods currently used need to be
      improved to ensure the full recovery of all children admitted.

PMID- 24277965
TI  - Clinical and mutation profile of children with cystic fibrosis in Jammu and
      Kashmir.
AB  - OBJECTIVE: To study the clinical and mutation profiles of children with cystic
      fibrosis in Jammu and Kashmir. METHODS: One hundred consecutive patients
      presenting with one or more phenotypic features suggestive of cystic fibrosis
      (CF) were screened by quantitative sweat chloride testing. For patients with
      positive/equivocal test result on two occasions, CFTR gene mutation analysis was
      done by polymerase chain reaction. RESULTS: Of the 100 patients, 18 (10 females)
      were diagnosed to have CF at a median age of 10.5 y (IQR 4.75-15.25 y) while the
      median age at the onset of symptoms was 12 mo (IQR 4-63 mo) with a delay in
      diagnosis by 102.4+/-80.5 months. Clinical features at presentation included
      failure to thrive (94.4%), chronic cough (78%), recurrent pneumonia (61%),
      persistent pneumonia (11%), and chronic diarrhea (50%). Positive sweat chloride
      (>60 meq/L) was seen in 14 (14%) patients and 4 (4%) patients had equivocal (40
      60 meq/L) value on two different occasions. Mutational analysis done in 15
      patients showed DeltaF508 mutation in 20% (3/15) patients in homozygous form and
      in 13% (2/15) patients in heterozygous form. Intron 19 mutation 3849+10kb C>T was
      found in 40% (6/15) in heterozygous form. One (6.6%) patient had DeltaF508 and
      3849+10kbC>T mutations in compound heterozygous form. Patients with equivocal
      sweat chloride and 3849+10kbC>T mutation had delayed onset of pulmonary
      involvement. CONCLUSION: 3849 +10kbC>T mutation appears to be common in children
      with cystic fibrosis in Jammu and Kashmir followed by DeltaF508, although the
      data are quite limited. Although presentation is delayed and sweat chloride is in
      the equivocal range, severe lung involvement may occur in these patients.

PMID- 24277966
TI  - Neonatal hearing screening--experience from a tertiary care hospital in southern
      India.
AB  - OBJECTIVE: To implement a neonatal hearing screening program using automated
      auditory brainstem response audiometry in a tertiary care set-up and assess the
      prevalence of neonatal hearing loss. DESIGN: Descriptive study. SETTING: Tertiary
      care hospital in Southern India. PARTICIPANTS: 9448 babies born in the hospital
      over a period of 11 months. INTERVENTION: The neonates were subjected to a two
      stage sequential screening using the BERAphone. Neonates suspected of hearing
      loss underwent confirmatory testing using auditory steady state response
      audiometry. In addition, serological testing for TORCH infections, and connexin
      26 gene was done. MAIN OUTCOME MEASURES: Feasibility of the screening program,
      prevalence of neonatal hearing loss and risk factors found in association with
      neonatal hearing loss. RESULTS: 164 babies were identified as suspected for
      hearing loss, but of which, only 58 visited the audiovestibular clinic. Among 45
      babies who had confirmatory testing, 39 were confirmed to have hearing loss and
      were rehabilitated appropriately. 30 babies had one or more risk factors; 6 had
      evidence of TORCH infection and 1 had connexin 26 gene mutation. CONCLUSION:
      Neonatal hearing screening using BERAphone is a feasible service. The estimated
      prevalence of confirmed hearing loss was comparable to that in literature.
      Overcoming the large numbers of loss to follow-up proves to be a challenge in the
      implementation of such a program.

PMID- 24277967
TI  - Heparin cofactor II thrombin complex as a biomarker for mucopolysaccharidosis:
      Indian experience.
AB  - BACKGROUND: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging
      biomarker for mucopolysaccharidosis disease (MPS I and MPS II). METHODS:
      Seventeen cases (6 MPS I and 11 MPS II) and sixty healthy controls were enrolled
      in study, conducted from September 2008 to December 2012. The mean +/- SD age of
      MPS1 (n=6, 5 males) and MPS II was 7.02 +/- 3.25 and 5.2 +/- 2.15 years,
      respectively. Disease status was confirmed by clinical features and enzyme assay.
      Urinary glycosaminoglycans were measured in spot urine samples and expressed in
      relation to creatinine content. HCIIT measurement was done using sandwich ELISA
      at enrolment and after 12 and 24 months of recruitment. RESULTS: Urinary
      glycosaminoglycans and HCIIT were elevated in all patients compared to their
      healthy controls. Both markers could not discriminate between the type of
      mucopolysaccharidosis. CONCLUSIONS: Heparin Cofactor II Thrombin Complex is a
      good biomarker for mucopolysaccharidosis I and II.

PMID- 24277968
TI  - Setting up a quality assurance model for newborn care to strengthen health system
      in Bihar, India.
AB  - BACKGROUND: A Quality Assurance model was rolled out in Bihar, India. It had two
      components: external and internal monitoring and giving feedback for action. The
      parameters included infrastructure and policy, equipment maintenance, stock
      supply and aseptic measures. METHODS: The performance and gradation into
      good/average/poor was measured based on the scores translated from the data
      collected after giving appropriate weights. RESULTS: 12%, 63%, and 25% units were
      categorized as good, average and poor based on infrastructure. For equipment, 68%
      of units performed poorly; for stock maintenance 64% and 35% of NBCCs fell under
      good and average categories respectively; most (54%) NBCCs had average scores for
      aseptic measures; 30% fell in the poor category. CONCLUSIONS: Involvement of
      government in monitoring and feedback mechanism, establishing a system of data
      collection at the grass root level and analysis at the state level were the
      positive outcomes.

PMID- 24277969
TI  - Effectiveness of anti scorpion venom for red scorpion envenomation.
AB  - OBJECTIVE: To study the efficacy of anti-scorpion venom plus prazocin. METHODS:
      Comparison of clinical features, outcome and duration of stay between children
      receiving anti-scorpion venom plus prazocin or prazocin alone for management of
      red scorpion envenomation. RESULTS: Requirement for dopamine and requirement and
      duration of dobutamine therapy were significantly less in patients received anti
      venom plus prazocin than those had prazocin only. Faster recovery was seen in
      cases who received anti-scorpion venom plus prazocin than prazocin only group.
      CONCLUSIONS: Anti-scorpion venom plus prazosin was safe and more effective than
      prazocin alone for scorpion envenomation.

PMID- 24277970
TI  - Reversibility of brainstem evoked response audiometry abnormalities at 3 months
      in term newborns with hyperbilirubinemia.
AB  - BACKGROUND: High bilirubin level is toxic to developing brain and auditory system
      but the current debate surrounds the toxicity of bilirubin in healthy term
      infants. METHODS: Longitudinal observational study to find BERA abnormalities in
      term newborns with isolated hyperbilirubinemia of 20 mg/dL and more and to follow
      up babies at 3 months to find out about the reversibility in BERA abnormalities
      noted at birth. RESULTS: BERA abnormalities were present in 17.64% of babies with
      isolated hyperbilirubinemia at discharge. There was a reversibility of BERA
      abnormalities in 61.61% during follow up. CONCLUSIONS: BERA abnormalities are
      reversible in term neonates with hyperbilirubinemia.

PMID- 24277971
TI  - Mediterranean diet for the prevention and treatment of metabolic syndrome: is it
      worth it?

PMID- 24277972
TI  - Irrational Blame.
AB  - I clarify some ambiguities in blame-talk and argue that blame's potential for
      irrationality and propensity to sting vitiates accounts of blame that identify it
      with consciously accessible, personal-level judgements or beliefs. Drawing on the
      cognitive psychology of emotion and appraisal theory, I develop an account of
      blame that accommodates these features. I suggest that blame consists in a range
      of hostile, negative first-order emotions, towards which the blamer has a
      specific, accompanying second-order attitude, namely, a feeling of entitlement -
      a feeling that these hostile, negative first-order emotions are what the blamed
      object deserves.

PMID- 24277973
TI  - Take time to smell the frogs: vocal sac glands of reed frogs (Anura:
      Hyperoliidae) contain species-specific chemical cocktails.
AB  - Males of all reed frog species (Anura: Hyperoliidae) have a prominent, often
      colourful, gular patch on their vocal sac, which is particularly conspicuous once
      the vocal sac is inflated. Although the presence, shape, and form of the gular
      patch are well-known diagnostic characters for these frogs, its function remains
      unknown. By integrating biochemical and histological methods, we found strong
      evidence that the gular patch is a gland producing volatile compounds, which
      might be emitted while calling. Volatile compounds were confirmed by gas
      chromatography-mass spectrometry in the gular glands in 11 species of the
      hyperoliid genera Afrixalus, Heterixalus, Hyperolius, and Phlyctimantis.
      Comparing the gular gland contents of 17 specimens of four sympatric Hyperolius
      species yielded a large variety of 65 compounds in species-specific combinations.
      We suggest that reed frogs might use a complex combination of at least acoustic
      and chemical signals in species recognition and mate choice.

PMID- 24277974
TI  - Elderly Homeless Veterans in Los Angeles: Chronicity and precipitants of
      homelessness.
AB  - We interviewed 33 chronically and 26 acutely homeless veterans aged 65 and over
      about their health and mental health, education and employment experience, social
      support, service needs and other precipitants of homelessness. Chronically
      homeless elderly veterans were more likely to have lower levels of education, had
      greater numbers and longer durations of prior homelessness, fewer social contacts
      providing instrumental support, and were more likely to report financial barriers
      to procuring housing. In response to open-ended questioning, elderly homeless
      veterans revealed how health and substance use issues interacted with loss of
      social support and eviction. The results suggest the importance of healthcare
      access and substance disorder treatment among elderly veterans and informs
      service delivery. Further research with larger samples is needed to confirm the
      characteristics and needs of the elderly homeless veteran population.

PMID- 24277975
TI  - Design of an Agent-Based Model to Examine Population-Environment Interactions in
      Nang Rong District, Thailand.
AB  - The design of an Agent-Based Model (ABM) is described that integrates Social and
      Land Use Modules to examine population-environment interactions in a former
      agricultural frontier in Northeastern Thailand. The ABM is used to assess
      household income and wealth derived from agricultural production of lowland, rain
      fed paddy rice and upland field crops in Nang Rong District as well as
      remittances returned to the household from family migrants who are engaged in off
      farm employment in urban destinations. The ABM is supported by a longitudinal
      social survey of nearly 10,000 households, a deep satellite image time-series of
      land use change trajectories, multi-thematic social and ecological data organized
      within a GIS, and a suite of software modules that integrate data derived from an
      agricultural cropping system model (DSSAT - Decision Support for Agrotechnology
      Transfer) and a land suitability model (MAXENT - Maximum Entropy), in addition to
      multi-dimensional demographic survey data of individuals and households. The
      primary modules of the ABM are the Initialization Module, Migration Module,
      Assets Module, Land Suitability Module, Crop Yield Module, Fertilizer Module, and
      the Land Use Change Decision Module. The architecture of the ABM is described
      relative to module function and connectivity through uni-directional or bi
      directional links. In general, the Social Modules simulate changes in human
      population and social networks, as well as changes in population migration and
      household assets, whereas the Land Use Modules simulate changes in land use
      types, land suitability, and crop yields. We emphasize the description of the
      Land Use Modules - the algorithms and interactions between the modules are
      described relative to the project goals of assessing household income and wealth
      relative to shifts in land use patterns, household demographics, population
      migration, social networks, and agricultural activities that collectively occur
      within a marginalized environment that is subjected to a suite of endogenous and
      exogenous dynamics.

PMID- 24277976
TI  - Does visual information influence infants' movement to music?
AB  - Humans are often exposed to music beginning at birth (or even before birth), yet
      the study of the development of musical abilities during infancy has only
      recently gained momentum. The goals of the present study were to determine
      whether young infants (ages four to seven months) spontaneously moved
      rhythmically in the presence of music, and whether the presence of visual
      information in addition to music would increase or decrease infants' movement.
      While nearly all infants moved in the presence of music, very few infants
      demonstrated rhythmic movement. Results revealed that, when visual information
      was present, and particularly when infants appeared to show focused attention
      toward the visual information, infants moved less than when only auditory
      information was present. The latter result is in agreement with most studies of
      sensory dominance in adults in which visual stimuli are dominant over auditory
      stimuli.

PMID- 24277977
TI  - Cooperation in Harsh Environments and the Emergence of Spatial Patterns.
AB  - This paper concerns the confluence of two important areas of research in
      mathematical biology: spatial pattern formation and cooperative dilemmas.
      Mechanisms through which social organisms form spatial patterns are not fully
      understood. Prior work connecting cooperation and pattern formation has often
      included unrealistic assumptions that shed doubt on the applicability of those
      models toward understanding real biological patterns. I investigated a more
      biologically realistic model of cooperation among social actors. The environment
      is harsh, so that interactions with cooperators are strictly needed to survive.
      Harshness is implemented via a constant energy deduction. I show that this model
      can generate spatial patterns similar to those seen in many naturally-occuring
      systems. Moreover, for each payoff matrix there is an associated critical value
      of the energy deduction that separates two distinct dynamical processes. In low
      harshness environments, the growth of cooperator clusters is impeded by
      defectors, but these clusters gradually expand to form dense dendritic patterns.
      In very harsh environments, cooperators expand rapidly but defectors can
      subsequently make inroads to form reticulated patterns. The resulting web-like
      patterns are reminiscent of transportation networks observed in slime mold
      colonies and other biological systems.

PMID- 24277978
TI  - Non-random brood mixing suggests adoption in a colonial cichlid.
AB  - Parental care of unrelated offspring is widespread but not well understood. We
      used 11 polymorphic microsatellite loci to investigate the relatedness of fry and
      parentally caring adults in a 118-nest colony of the socially and genetically
      monogamous cichlid fish Neolamprologus caudopunctatus in Lake Tanganyika. There
      was a high proportion of brood mixing, with 59% of 32 broods containing fry
      unrelated to both parents, and 18% of all 291 sampled fry being unrelated to the
      breeding pair. There was no evidence of kin selection for adoption because the
      genetic and foster parents were not more related than expected by chance.
      Parentage was assigned to 12 adopted fry from 10 broods. Distances traversed by
      fry varied markedly, from less than one to over 40 meters. The larger distances
      suggest that at least some brood mixing was instigated by parents transporting
      portions of their broods in their mouths, as occurs in some cichlids. Further
      evidence of non-random brood mixing was that foreign fry did not differ in size
      from their foster siblings within broods, even though they were significantly
      larger than fry produced by the tending pairs within the colony. These findings
      suggest that at least some foreign fry had dispersed non-randomly and were
      adopted by their foster parents. Enlarged broods are known to provide reduced per
      capita predation, making it potentially adaptive for breeders to adopt unrelated
      offspring.

PMID- 24277979
TI  - Evidence of traditional knowledge loss among a contemporary indigenous society.
AB  - As biological and linguistic diversity, the world's cultural diversity is on
      decline. However, to date there are no estimates of the rate at which the
      specific cultural traits of a group disappear, mainly because we lack empirical
      data to assess how the cultural traits of a given population change over time.
      Here we estimate changes in cultural traits associated to the traditional
      knowledge of wild plant uses among an Amazonian indigenous society. We collected
      data among 1151 Tsimane' Amerindians at two periods of time. Results show that
      between 2000 and 2009, Tsimane' adults experienced a net decrease in the report
      of plant uses ranging from 9% (for the female subsample) to 26% (for the
      subsample of people living close to towns), equivalent to a 1 to 3 % per year.
      Results from a Monte Carlo simulation show that the observed changes were not the
      result of randomness. Changes were more acute for men than for women and for
      informants living in villages close to market towns than for informants settled
      in remote villages. The Tsimane' could be abandoning their traditional knowledge
      as they perceive that this form of knowledge do not equip them well to deal with
      the new socio-economic and cultural conditions they face nowadays.

PMID- 24277980
TI  - The origin of parasitism gene in nematodes: evolutionary analysis through the
      construction of domain trees.
AB  - Inferring evolutionary history of parasitism genes is important to understand how
      evolutionary mechanisms affect the occurrences of parasitism genes. In this
      study, we constructed multiple domain trees for parasitism genes and genes under
      free-living conditions. Further analyses of horizontal gene transfer (HGT)-like
      phylogenetic incongruences, duplications, and speciations were performed based on
      these trees. By comparing these analyses, the contributions of pre-adaptations
      were found to be more important to the evolution of parasitism genes than those
      of duplications, and pre-adaptations are as crucial as previously reported HGTs
      to parasitism. Furthermore, speciation may also affect the evolution of
      parasitism genes. In addition, Pristionchus pacificus was suggested to be a
      common model organism for studies of parasitic nematodes, including root-knot
      species. These analyses provided information regarding mechanisms that may have
      contributed to the evolution of parasitism genes. 

PMID- 24277981
TI  - Grouped False-Discovery Rate for Removing the Gene-Set-Level Bias of RNA-seq.
AB  - In recent years, RNA-seq has become a very competitive alternative to
      microarrays. In RNA-seq experiments, the expected read count for a gene is
      proportional to its expression level multiplied by its transcript length. Even
      when two genes are expressed at the same level, differences in length will yield
      differing numbers of total reads. The characteristics of these RNA-seq
      experiments create a gene-level bias such that the proportion of significantly
      differentially expressed genes increases with the transcript length, whereas such
      bias is not present in microarray data. Gene-set analysis seeks to identify the
      gene sets that are enriched in the list of the identified significant genes. In
      the gene-set analysis of RNA-seq, the gene-level bias subsequently yields the
      gene-set-level bias that a gene set with genes of long length will be more likely
      to show up as enriched than will a gene set with genes of shorter length. Because
      gene expression is not related to its transcript length, any gene set containing
      long genes is not of biologically greater interest than gene sets with shorter
      genes. Accordingly the gene-set-level bias should be removed to accurately
      calculate the statistical significance of each gene-set enrichment in the RNA
      seq. We present a new gene set analysis method of RNA-seq, called FDRseq, which
      can accurately calculate the statistical significance of a gene-set enrichment
      score by the grouped false-discovery rate. Numerical examples indicated that
      FDRseq is appropriate for controlling the transcript length bias in the gene-set
      analysis of RNA-seq data. To implement FDRseq, we developed the R program, which
      can be downloaded at no cost from
      http://home.mju.ac.kr/home/index.action?siteId=tyang. 

PMID- 24277982
TI  - Quantification of Plasma miRNAs by Digital PCR for Cancer Diagnosis.
AB  - Analysis of plasma microRNAs (miRNAs) by quantitative polymerase chain reaction
      (qPCR) provides a potential approach for cancer diagnosis. However, absolutely
      quantifying low abundant plasma miRNAs is challenging with qPCR. Digital PCR
      offers a unique means for assessment of nucleic acids presenting at low levels in
      plasma. This study aimed to evaluate the efficacy of digital PCR for
      quantification of plasma miRNAs and the potential utility of this technique for
      cancer diagnosis. We used digital PCR to quantify the copy number of plasma
      microRNA-21-5p (miR-21-5p) and microRNA-335-3p (miR-335-3p) in 36 lung cancer
      patients and 38 controls. Digital PCR showed a high degree of linearity and
      quantitative correlation with miRNAs in a dynamic range from 1 to 10,000
      copies/MUL of input, with high reproducibility. qPCR exhibited a dynamic range
      from 100 to 1*10(7) copies/MUL of input. Digital PCR had a higher sensitivity to
      detect copy number of the miRNAs compared with qPCR. In plasma, digital PCR could
      detect copy number of both miR-21-5p and miR-335-3p, whereas qPCR was only able
      to assess miR-21-5p. Quantification of the plasma miRNAs by digital PCR provided
      71.8% sensitivity and 80.6% specificity in distinguishing lung cancer patients
      from cancer-free subjects. 

PMID- 24277983
TI  - Epidemiological and mortality analysis of older adults with HIV in eastern China.
AB  - OBJECTIVE: The aims of this study were to systematically review epidemiological
      characteristics in older people living with human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) (PLWHA) in low endemic areas of the People's
      Republic of China, analyze the causes of death and mortality, and provide a basis
      for targeted prevention in these populations. METHODS: Nine counties
      representative of the distribution and epidemiological factors of the HIV
      epidemic in Zhejiang Province were selected, and data from 1,115 HIV-positive
      individuals, including 196 older people (>=50 years), who were confirmed as PLWHA
      from January 1, 2000 to December 31, 2012, were retrospectively analyzed.
      RESULTS: The proportion of older PLWHA increased from 0% in 2000 to 22.45% in
      2012. Sexual transmission was the main route, accounting for 82.65% of infections
      in this group. Compared with the younger group (range from 14 to 49 years old),
      the older group had significantly lower CD4+ cell counts (291.64 versus 363.63;
      P<0.001) when first diagnosed, and more of this group presented in the AIDS state
      with opportunistic infections (51.02% versus 34.06%; P<0.001). In the older
      group, 25 (12.76%) patients died directly of AIDS and 171 (87.24%) were censored,
      and in the younger group 50 (5.44%) patients died directly of AIDS and 869
      (94.56%) were censored. Estimated survival time since HIV diagnosis in the older
      group was 11.54+/-0.49 years (95% confidence interval [CI] 10.59-12.50), while in
      the younger group it was 13.85+/-0.46 years (95% CI 12.94-14.76), the log rank
      (Mantel-Cox) test gave a chi-square value of 3.83, and there was significant
      difference between the groups (P<0.05). CONCLUSION: The number of older PLWHA
      increased steadily over the study period in low HIV endemic provinces of a
      developing country. Later discovery and preexisting disease perhaps contributed
      to a shorter estimated survival time for older PLWHA and higher mortality.

PMID- 24277984
TI  - Detection of suicide among the elderly in a long term care facility.
AB  - PURPOSE: The aim of this study was to establish the level of correlation between
      the suicide item contained within the Core Symptom Index (CSI), and the presence
      of suicidal thoughts as assessed by the Mini-International Neuropsychiatric
      Interview (MINI) and the Cornell Scale of Depression in Dementia (CSDD). PATIENTS
      AND METHODS: Seventy elderly residents in a long term care facility were included
      in this study. All of these patients completed a CSI and a geriatric depression
      scale (GDS), plus were interviewed using CSDD, MINI (suicide module), and MMSE.
      Test characteristics of item two of the CSI (suicidal thoughts) and MINI were
      compared. Gwet's AC1 and Cohen's Kappa were also used to test the level of
      agreement between raters, and univariate analysis was used to determine
      predictors for the severity of any suicidal thoughts present. RESULTS: There was
      found to be a significant correlation between suicidal ideation, as assessed by
      item two of the CSI, and the suicidal ideation score as assessed by MINI and CSDD
      (r=0.773 and r=0.626, P<0.001, respectively). The level of agreement across all
      three instruments was good (Gwet's AC1 =0.907). The CSI yielded a high level of
      sensitivity (100%) and specificity (90.32%) for suicidal thoughts as measured by
      MINI, with an area under the curve of 97%. When assessing predictors of the
      severity of suicidal thoughts, only item two of the CSI predicted severity, while
      the depression, GDS, and total scores obtained from the CSI did not. CONCLUSION:
      CSI item two has the ability to detect suicidal ideation, regardless of whether
      the patient has cognitive impairment and/or depression or not, and is currently
      the best predictor of its presence. Therefore, it shows promise as a measure for
      screening the presence of suicidal thoughts among the elderly in long term care
      facilities.

PMID- 24277985
TI  - The health care burden of high grade chronic obstructive pulmonary disease in
      Korea: analysis of the Korean Health Insurance Review and Assessment Service
      data.
AB  - BACKGROUND: Patients with high grade chronic pulmonary obstructive disease (COPD)
      account for much of the COPD-related mortality and incur excessive financial
      burdens and medical care utilization. We aimed to determine the characteristics
      and medical care use of such patients using nationwide data from the Korean
      Health Insurance Review and Assessment Service in 2009. MATERIALS AND METHODS:
      Patients with COPD were identified by searching with the International
      Classification of Diseases-10th Revision for those using medication. Patients
      with high grade COPD were selected based on their patterns of tertiary institute
      visits and medication use. RESULTS: The numbers of patients with high grade COPD
      increased rapidly in Korea during the study period, and they showed a high
      prevalence of comorbid disease. The total medical costs were over three times
      higher in patients with high grade COPD compared with those without it ($3,744
      versus $1,183; P < 0.001). Medication costs comprised the largest portion of
      medical cost, but most impact came from hospitalization and exacerbation in both
      groups of patients. COPD grade and hospitalization in the previous year were the
      major factors affecting medical costs and days of utilizing health care
      resources. CONCLUSION: Patients with high grade COPD impose a high economic
      burden on the health care system in Korea. Prevention of progression to high
      grade COPD is important, both clinically and economically.

PMID- 24277986
TI  - Mechanisms of microemulsion enhancing the oral bioavailability of puerarin:
      comparison between oil-in-water and water-in-oil microemulsions using the single
      pass intestinal perfusion method and a chylomicron flow blocking approach.
AB  - The purpose of the present work was to determine the mechanisms by which
      microemulsions (MEs) enhance the oral bioavailability of puerarin. The in situ
      perfusion method was used in rats to study the absorption mechanisms of an oil-in
      water (O/W) microemulsion (O/W-ME) and a water-in-oil (W/O) microemulsion (W/O
      ME). The possibility of lymphatic transport of the MEs was investigated using a
      chylomicron flow blocking approach. The results for the absorption mechanisms in
      the stomach and intestines indicated that the absorption characteristics of the
      O/W-ME and W/O-ME depend on the segment. The W/O-ME had higher internal membrane
      permeability than the O/W-ME. The results of the lymphatic transport analyses
      showed that both the O/W-ME and W/O-ME underwent lymphatic transport and that
      this pathway was a major contributor to the oral bioavailability of MEs.
      Furthermore, the type of ME can significantly affect the absorption of puerarin
      through the lymphatic system due to the oil content and the form of the
      microemulsion after oral administration. In conclusion, these data indicate that
      microemulsions are an effective and promising delivery system to enhance the oral
      bioavailability of poorly water-soluble drugs. 

PMID- 24277987
TI  - Drug-loading capacity and nuclear targeting of multiwalled carbon nanotubes
      grafted with anionic amphiphilic copolymers.
AB  - In this study, three types of hybrid nanotubes (NTs), ie, oxidized multiwalled
      carbon NTs (COOH MWCNTs), heparin (Hep)-conjugated MWCNTs (Hep MWCNTs), and
      diblock copolymer polyglycolic acid (PGA)-co-heparin conjugated to MWCNTs (PGA
      MWCNTs), were synthesized with improved biocompatibility and drug-loading
      capacity. Hydrophilic Hep substituents on MWCNTs improved biocompatibility and
      acted as nucleus-sensitive segments on the CNT carrier, whereas the addition of
      PGA enhanced drug-loading capacity. In the PGA MWCNT system, the amphiphilic
      copolymer (PGA-Hep) formed micelles on the side walls of CNTs, as confirmed by
      electron microscopy. The PGA system encapsulated the hydrophobic drug with high
      efficiency compared to the COOH MWCNT and Hep MWCNT systems. This is because the
      drug was loaded onto the PGA MWCNTs through hydrophobic forces and onto the CNTs
      by pi-pi stacking interactions. Additionally, most of the current drug-carrier
      designs that target cancer cells release the drug in the lysosome or cytoplasm.
      However, nuclear-targeted drug release is expected to kill cancer cells more
      directly and efficiently. In our study, PGA MWCNT carriers effectively delivered
      the active anticancer drug doxorubicin into targeted nuclei. This study may
      provide an effective strategy for the development of carbon-based drug carriers
      for nuclear-targeted drug delivery. 

PMID- 24277988
TI  - Influenza treatment and prophylaxis with neuraminidase inhibitors: a review.
AB  - Influenza virus is a pathogen that causes morbidity and mortality worldwide.
      Whereas vaccination is important for prevention of disease, given its
      limitations, antiviral therapy is at the forefront of treatment and also plays a
      role in prevention. Currently, two classes of antiviral medications, the
      adamantanes and the neuraminidase inhibitors, are approved for treatment. Given
      the resistance patterns of circulating influenza, adamantanes are not
      recommended. Within the US, two neuraminidase inhibitors are currently approved
      for both treatment and prevention, while worldwide there are four available. In
      this review, we will briefly discuss the epidemiology and pathology of influenza
      and then discuss neuraminidase inhibitors: their mechanism of action, resistance,
      development, and future applications. 

PMID- 24277989
TI  - Persistence with weekly and monthly bisphosphonates among postmenopausal women:
      analysis of a US pharmacy claims administrative database.
AB  - BACKGROUND: Bisphosphonates are available in daily, weekly, and monthly dosing
      formulations to treat postmenopausal osteoporosis. Some researchers suggested
      that adherence to monthly bisphosphonate might be different from that with weekly
      or daily bisphosphonate because of different dosing regimens. However, the actual
      persistency rates in regular practice settings are unknown. OBJECTIVES: To
      compare persistence rates with alendronate 70 mg once weekly (AOW), risedronate
      35 mg once weekly (ROW), and ibandronate 150 mg once monthly (IOM) in a US
      pharmacy claims database. METHODS: In this retrospective cohort study, pharmacy
      claims data of patients with new bisphosphonate prescriptions were extracted for
      women aged >= 50 years who had an AOW, ROW, or IOM prescription (index
      prescription) between December 30, 2004 and May 31, 2005 (the index period) and
      did not have the index Rx during the previous 12 months. Patients' records were
      reviewed for at least 5 months from their index date to November 2, 2005 (the
      follow-up period). Patients were considered persistent if they neither
      discontinued (failed to refill the index Rx within a 45-day period following the
      last supply day of the previous dispensing) nor switched (changed to another
      bisphosphonate) during the follow-up period. Medication-possession ratio was
      defined as days with index prescription supplies/total days of follow-up.
      RESULTS: Among 44,635 patients, 25,207 (56.5%) received prescriptions of AOW,
      18,689 (41.9%) ROW, and 739 (1.7%) IOM as the index prescription. In all, 35.1%
      of AOW patients, 32.5% of ROW patients, and 30.4% of IOM patients (P < 0.0001 AOW
      vs ROW or IOM) had persisted with their initial therapy, whereas 64.0% of AOW,
      66.4% of ROW, and 68.2% of IOM patients discontinued (P < 0.0001) during follow
      up. The medication-possession ratio (days with index prescription supplies/total
      days of follow-up) was significantly higher for AOW (0.55) compared with ROW
      (0.52) and IOM (0.51, P < 0.05). By Kaplan-Meier analysis, the time for 50% of
      patients to discontinue therapy was also significantly longer with AOW (109 days)
      compared with ROW (95 days, P < 0.05) or IOM (58 days, P < 0.05). CONCLUSION: In
      a real-world clinical setting, although persistence with all treatments was
      suboptimal, patients receiving prescriptions for once-weekly alendronate were
      more likely to be persistent than those receiving prescriptions for once-weekly
      risedronate or once-monthly ibandronate.

PMID- 24277990
TI  - Overcoming technical challenges when treating atypical hemolytic uremic syndrome
      with therapeutic plasma exchange.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a very rare, life-threatening,
      progressive disease that frequently has a genetic component and in most cases is
      triggered by an uncontrolled activation of the complement system. Successful
      treatment of aHUS with plasma infusions and therapeutic plasma exchange (TPE) is
      well reported. TPE has been the treatment of choice in most adult patients with
      aHUS. However, due to severe hemolysis, which is common among aHUS patients,
      there are some technical challenges that can affect TPE treatment such as the
      continuous activation of the blood leak alarm due to hemolysis. Our experience
      shows that such patients can be managed better on a centrifuge based TPE machine
      compared to a membrane based TPE machine. 

PMID- 24277991
TI  - Preliminary study about the possible glycemic clinical advantage in using a fixed
      combination of Berberis aristata and Silybum marianum standardized extracts
      versus only Berberis aristata in patients with type 2 diabetes.
AB  - BACKGROUND: Berberine is an isoquinoline alkaloid widely used to improve the
      glucidic and lipidic profiles of patients with hypercholesterolemia, metabolic
      syndrome, and type 2 diabetes. The limitation of berberine seems to be its poor
      oral bioavailability, which is affected by the presence, in enterocytes, of P
      glycoprotein - an active adenosine triphosphate (ATP)-consuming efflux protein
      that extrudes berberine into the intestinal lumen, thus limiting its absorption.
      According to some authors, silymarin, derived from Silybum marianum, could be
      considered a P-glycoprotein antagonist. AIM: The study aimed to evaluate the role
      played by a possible P-glycoprotein antagonist (silymarin), when added to a
      product containing Berberis aristata extract, in terms of benefits to patients
      with type 2 diabetes. METHODS: The study enrolled 69 patients with type 2
      diabetes in suboptimal glycemic control who were treated with diet, hypoglycemic
      drugs, and in cases of concomitant alterations of the lipid profile,
      hypolipidemic agents. The patients received an add-on therapy consisting of
      either a standardized extract of Berberis aristata (titrated in 85% berberine)
      corresponding to 1,000 mg/day of berberine, or Berberol(r), a fixed combination
      containing the same standardized extract of Berberis aristata plus a standardized
      extract of Silybum marianum (titrated as >60% in silymarin), for a total intake
      of 1,000 mg/day of berberine and 210 mg/day of silymarin. RESULTS: Both
      treatments similarly improved fasting glucose, total cholesterol, low-density
      lipoprotein (LDL) cholesterol, triglyceride, and liver enzyme levels, whereas
      glycosylated hemoglobin (HbA1c) values were reduced to a greater extent by the
      fixed combination. CONCLUSION: The association of berberine and silymarin
      demonstrated to be more effective than berberine alone in reducing HbA1c, when
      administered at the same dose and in the form of standardized extracts in type 2
      diabetic patients.

PMID- 24277992
TI  - Investigation of the donor and acceptor range for chiral carboligation catalyzed
      by the E1 component of the 2-oxoglutarate dehydrogenase complex.
AB  - The potential of thiamin diphosphate (ThDP)-dependent enzymes to catalyze C-C
      bond forming (carboligase) reactions with high enantiomeric excess has been
      recognized for many years. Here we report the application of the E1 component of
      the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex in the
      synthesis of chiral compounds with multiple functional groups in good yield and
      high enantiomeric excess, by varying both the donor substrate (different 2-oxo
      acids) and the acceptor substrate (glyoxylate, ethyl glyoxylate and methyl
      glyoxal). Major findings include the demonstration that the enzyme can accept 2
      oxovalerate and 2-oxoisovalerate in addition to its natural substrate 2
      oxoglutarate, and that the tested acceptors are also acceptable in the
      carboligation reaction, thereby very much expanding the repertory of the enzyme
      in chiral synthesis.

PMID- 24277993
TI  - Bilingual Two-Way Immersion Programs Benefit Academic Achievement.
AB  - The effects of bilingual education on reading and math achievement were examined
      by comparing test scores across different elementary-school programs. Results
      revealed that bilingual Two-Way Immersion programs benefited both minority
      language and majority-language students. Minority-language students in Two-Way
      Immersion outperformed their peers in Transitional Programs of Instruction, while
      majority-language students in Two-Way Immersion outperformed their peers in
      Mainstream monolingual classrooms. Bilingual Two-Way Immersion programs may
      enhance reading and math skills in both minority-language and majority-language
      elementary-school children.

PMID- 24277995
TI  - Identification of key hinge residues important for nucleotide-dependent allostery
      in E. coli Hsp70/DnaK.
AB  - DnaK is a molecular chaperone that has important roles in protein folding. The
      hydrolysis of ATP is essential to this activity, and the effects of nucleotides
      on the structure and function of DnaK have been extensively studied. However, the
      key residues that govern the conformational motions that define the apo, ATP
      bound, and ADP-bound states are not entirely clear. Here, we used molecular
      dynamics simulations, mutagenesis, and enzymatic assays to explore the molecular
      basis of this process. Simulations of DnaK's nucleotide-binding domain (NBD) in
      the apo, ATP-bound, and ADP/Pi-bound states suggested that each state has a
      distinct conformation, consistent with available biochemical and structural
      information. The simulations further suggested that large shearing motions
      between subdomains I-A and II-A dominated the conversion between these
      conformations. We found that several evolutionally conserved residues, especially
      G228 and G229, appeared to function as a hinge for these motions, because they
      predominantly populated two distinct states depending on whether ATP or ADP/Pi
      was bound. Consistent with the importance of these "hinge" residues, alanine
      point mutations caused DnaK to have reduced chaperone activities in vitro and in
      vivo. Together, these results clarify how sub-domain motions communicate
      allostery in DnaK. 

PMID- 24277996
TI  - Cell-based multi-parametric model of cleft progression during submandibular
      salivary gland branching morphogenesis.
AB  - Cleft formation during submandibular salivary gland branching morphogenesis is
      the critical step initiating the growth and development of the complex adult
      organ. Previous experimental studies indicated requirements for several
      epithelial cellular processes, such as proliferation, migration, cell-cell
      adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction
      in cleft formation; however, the relative contribution of each of these processes
      is not fully understood since it is not possible to experimentally manipulate
      each factor independently. We present here a comprehensive analysis of several
      cellular parameters regulating cleft progression during branching morphogenesis
      in the epithelial tissue of an early embryonic salivary gland at a local scale
      using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg
      model. We utilized measurements from time-lapse images of mouse submandibular
      gland organ explants to construct a temporally and spatially relevant cell-based
      2D model. Our model simulates the effect of cellular proliferation, actomyosin
      contractility, cell-cell and cell-matrix adhesions on cleft progression, and it
      was used to test specific hypotheses regarding the function of these parameters
      in branching morphogenesis. We use innovative features capturing several aspects
      of cleft morphology and quantitatively analyze clefts formed during functional
      modification of the cellular parameters. Our simulations predict that a low
      epithelial mitosis rate and moderate level of actomyosin contractility in the
      cleft cells promote cleft progression. Raising or lowering levels of
      contractility and mitosis rate resulted in non-progressive clefts. We also show
      that lowered cell-cell adhesion in the cleft region and increased cleft cell
      matrix adhesions are required for cleft progression. Using a classifier-based
      analysis, the relative importance of these four contributing cellular factors for
      effective cleft progression was determined as follows: cleft cell contractility,
      cleft region cell-cell adhesion strength, epithelial cell mitosis rate, and cell
      matrix adhesion strength. 

PMID- 24277997
TI  - Exploring the composition of protein-ligand binding sites on a large scale.
AB  - The residue composition of a ligand binding site determines the interactions
      available for diffusion-mediated ligand binding, and understanding general
      composition of these sites is of great importance if we are to gain insight into
      the functional diversity of the proteome. Many structure-based drug design
      methods utilize such heuristic information for improving prediction or
      characterization of ligand-binding sites in proteins of unknown function. The
      Binding MOAD database if one of the largest curated sets of protein-ligand
      complexes, and provides a source of diverse, high-quality data for establishing
      general trends of residue composition from currently available protein
      structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non
      redundant binding sites to identify residues over-represented in binding regions
      versus the rest of the protein surface. The Binding MOAD database delineates
      biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound
      to the protein. Invalids are present in the crystallization medium and serve no
      known biological function. Contacts are found to differ between these classes of
      ligands, indicating that residue composition of biologically relevant binding
      sites is distinct not only from the rest of the protein surface, but also from
      surface regions capable of opportunistic binding of non-functional small
      molecules. To confirm these trends, we perform a rigorous analysis of the
      variation of residue propensity with respect to the size of the dataset and the
      content bias inherent in structure sets obtained from a large protein structure
      database. The optimal size of the dataset for establishing general trends of
      residue propensities, as well as strategies for assessing the significance of
      such trends, are suggested for future studies of binding-site composition. 

PMID- 24277998
TI  - A data-driven mathematical model of CA-MRSA transmission among age groups:
      evaluating the effect of control interventions.
AB  - Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has
      become a major cause of skin and soft tissue infections (SSTIs) in the US. We
      developed an age-structured compartmental model to study the spread of CA-MRSA at
      the population level and assess the effect of control intervention strategies. We
      used Monte-Carlo Markov Chain (MCMC) techniques to parameterize our model using
      monthly time series data on SSTIs incidence in children (<= 19 years) during
      January 2004 -December 2006 in Maricopa County, Arizona. Our model-based forecast
      for the period January 2007-December 2008 also provided a good fit to data. We
      also carried out an uncertainty and sensitivity analysis on the control
      reproduction number, Rc which we estimated at 1.3 (95% CI [1.2,1.4]) based on the
      model fit to data. Using our calibrated model, we evaluated the effect of typical
      intervention strategies namely reducing the contact rate of infected individuals
      owing to awareness of infection and decolonization strategies targeting
      symptomatic infected individuals on both [Formula: see text] and the long-term
      disease dynamics. We also evaluated the impact of hypothetical decolonization
      strategies targeting asymptomatic colonized individuals. We found that strategies
      focused on infected individuals were not capable of achieving disease control
      when implemented alone or in combination. In contrast, our results suggest that
      decolonization strategies targeting the pediatric population colonized with CA
      MRSA have the potential of achieving disease elimination.

PMID- 24277999
TI  - Dread and the disvalue of future pain.
AB  - Standard theories of decision-making involving delayed outcomes predict that
      people should defer a punishment, whilst advancing a reward. In some cases, such
      as pain, people seem to prefer to expedite punishment, implying that its
      anticipation carries a cost, often conceptualized as 'dread'. Despite empirical
      support for the existence of dread, whether and how it depends on prospective
      delay is unknown. Furthermore, it is unclear whether dread represents a stable
      component of value, or is modulated by biases such as framing effects. Here, we
      examine choices made between different numbers of painful shocks to be delivered
      faithfully at different time points up to 15 minutes in the future, as well as
      choices between hypothetical painful dental appointments at time points of up to
      approximately eight months in the future, to test alternative models for how
      future pain is disvalued. We show that future pain initially becomes increasingly
      aversive with increasing delay, but does so at a decreasing rate. This is
      consistent with a value model in which moment-by-moment dread increases up to the
      time of expected pain, such that dread becomes equivalent to the discounted
      expectation of pain. For a minority of individuals pain has maximum negative
      value at intermediate delay, suggesting that the dread function may itself be
      prospectively discounted in time. Framing an outcome as relief reduces the
      overall preference to expedite pain, which can be parameterized by reducing the
      rate of the dread-discounting function. Our data support an account of
      disvaluation for primary punishments such as pain, which differs fundamentally
      from existing models applied to financial punishments, in which dread exerts a
      powerful but time-dependent influence over choice. 

PMID- 24278000
TI  - Genetic architecture promotes the evolution and maintenance of cooperation.
AB  - When cooperation has a direct cost and an indirect benefit, a selfish behavior is
      more likely to be selected for than an altruistic one. Kin and group selection do
      provide evolutionary explanations for the stability of cooperation in nature, but
      we still lack the full understanding of the genomic mechanisms that can prevent
      cheater invasion. In our study we used Aevol, an agent-based, in silico genomic
      platform to evolve populations of digital organisms that compete, reproduce, and
      cooperate by secreting a public good for tens of thousands of generations. We
      found that cooperating individuals may share a phenotype, defined as the amount
      of public good produced, but have very different abilities to resist cheater
      invasion. To understand the underlying genetic differences between cooperator
      types, we performed bio-inspired genomics analyses of our digital organisms by
      recording and comparing the locations of metabolic and secretion genes, as well
      as the relevant promoters and terminators. Association between metabolic and
      secretion genes (promoter sharing, overlap via frame shift or sense-antisense
      encoding) was characteristic for populations with robust cooperation and was more
      likely to evolve when secretion was costly. In mutational analysis experiments,
      we demonstrated the potential evolutionary consequences of the genetic
      association by performing a large number of mutations and measuring their
      phenotypic and fitness effects. The non-cooperating mutants arising from the
      individuals with genetic association were more likely to have metabolic
      deleterious mutations that eventually lead to selection eliminating such mutants
      from the population due to the accompanying fitness decrease. Effectively,
      cooperation evolved to be protected and robust to mutations through entangled
      genetic architecture. Our results confirm the importance of second-order
      selection on evolutionary outcomes, uncover an important genetic mechanism for
      the evolution and maintenance of cooperation, and suggest promising methods for
      preventing gene loss in synthetically engineered organisms. 

PMID- 24278001
TI  - Ten simple rules for starting a regional student group.

PMID- 24278002
TI  - Assessing computational methods for transcription factor target gene
      identification based on ChIP-seq data.
AB  - Chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) has great
      potential for elucidating transcriptional networks, by measuring genome-wide
      binding of transcription factors (TFs) at high resolution. Despite the precision
      of these experiments, identification of genes directly regulated by a TF (target
      genes) is not trivial. Numerous target gene scoring methods have been used in the
      past. However, their suitability for the task and their performance remain
      unclear, because a thorough comparative assessment of these methods is still
      lacking. Here we present a systematic evaluation of computational methods for
      defining TF targets based on ChIP-seq data. We validated predictions based on 68
      ChIP-seq studies using a wide range of genomic expression data and functional
      information. We demonstrate that peak-to-gene assignment is the most crucial step
      for correct target gene prediction and propose a parameter-free method performing
      most consistently across the evaluation tests. 

PMID- 24278003
TI  - Systematic analysis of compositional order of proteins reveals new
      characteristics of biological functions and a universal correlate of
      macroevolution.
AB  - We present a novel analysis of compositional order (CO) based on the occurrence
      of Frequent amino-acid Triplets (FTs) that appear much more than random in
      protein sequences. The method captures all types of proteomic compositional order
      including single amino-acid runs, tandem repeats, periodic structure of motifs
      and otherwise low complexity amino-acid regions. We introduce new order measures,
      distinguishing between 'regularity', 'periodicity' and 'vocabulary', to quantify
      these phenomena and to facilitate the identification of evolutionary effects.
      Detailed analysis of representative species across the tree-of-life demonstrates
      that CO proteins exhibit numerous functional enrichments, including a wide
      repertoire of particular patterns of dependencies on regularity and periodicity.
      Comparison between human and mouse proteomes further reveals the interplay of CO
      with evolutionary trends, such as faster substitution rate in mouse leading to
      decrease of periodicity, while innovation along the human lineage leads to larger
      regularity. Large-scale analysis of 94 proteomes leads to systematic ordering of
      all major taxonomic groups according to FT-vocabulary size. This is measured by
      the count of Different Frequent Triplets (DFT) in proteomes. The latter provides
      a clear hierarchical delineation of vertebrates, invertebrates, plants, fungi and
      prokaryotes, with thermophiles showing the lowest level of FT-vocabulary. Among
      eukaryotes, this ordering correlates with phylogenetic proximity. Interestingly,
      in all kingdoms CO accumulation in the proteome has universal characteristics. We
      suggest that CO is a genomic-information correlate of both macroevolution and
      various protein functions. The results indicate a mechanism of genomic
      'innovation' at the peptide level, involved in protein elongation, shaped in a
      universal manner by mutational and selective forces. 

PMID- 24278004
TI  - MicroRNA-gene association as a prognostic biomarker in cancer exposes disease
      mechanisms.
AB  - The transcriptional networks that regulate gene expression and modifications to
      this network are at the core of the cancer phenotype. MicroRNAs, a well-studied
      species of small non-coding RNA molecules, have been shown to have a central role
      in regulating gene expression as part of this transcriptional network. Further,
      microRNA deregulation is associated with cancer development and with tumor
      progression. Glioblastoma Multiform (GBM) is the most common, aggressive and
      malignant primary tumor of the brain and is associated with one of the worst 5
      year survival rates among all human cancers. To study the transcriptional network
      and its modifications in GBM, we utilized gene expression, microRNA sequencing,
      whole genome sequencing and clinical data from hundreds of patients from
      different datasets. Using these data and a novel microRNA-gene association
      approach we introduce, we have identified unique microRNAs and their associated
      genes. This unique behavior is composed of the ability of the quantifiable
      association of the microRNA and the gene expression levels, which we show
      stratify patients into clinical subgroups of high statistical significance.
      Importantly, this stratification goes unobserved by other methods and is not
      affiliated by other subsets or phenotypes within the data. To investigate the
      robustness of the introduced approach, we demonstrate, in unrelated datasets,
      robustness of findings. Among the set of identified microRNA-gene associations,
      we closely study the example of MAF and hsa-miR-330-3p, and show how their co
      behavior stratifies patients into prognosis clinical groups and how whole genome
      sequences tells us more about a specific genomic variation as a possible basis
      for patient variances. We argue that these identified associations may indicate
      previously unexplored specific disease control mechanisms and may be used as
      basis for further study and for possible therapeutic intervention. 

PMID- 24278005
TI  - Understanding the connection between epigenetic DNA methylation and nucleosome
      positioning from computer simulations.
AB  - Cytosine methylation is one of the most important epigenetic marks that regulate
      the process of gene expression. Here, we have examined the effect of epigenetic
      DNA methylation on nucleosomal stability using molecular dynamics simulations and
      elastic deformation models. We found that methylation of CpG steps destabilizes
      nucleosomes, especially when these are placed in sites where the DNA minor groove
      faces the histone core. The larger stiffness of methylated CpG steps is a crucial
      factor behind the decrease in nucleosome stability. Methylation changes the
      positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA
      to regulatory proteins, and accordingly gene functionality. Our theoretical
      calculations highlight a simple physical-based explanation on the foundations of
      epigenetic signaling. 

PMID- 24278006
TI  - Beyond GLMs: a generative mixture modeling approach to neural system
      identification.
AB  - Generalized linear models (GLMs) represent a popular choice for the probabilistic
      characterization of neural spike responses. While GLMs are attractive for their
      computational tractability, they also impose strong assumptions and thus only
      allow for a limited range of stimulus-response relationships to be discovered.
      Alternative approaches exist that make only very weak assumptions but scale
      poorly to high-dimensional stimulus spaces. Here we seek an approach which can
      gracefully interpolate between the two extremes. We extend two frequently used
      special cases of the GLM-a linear and a quadratic model-by assuming that the
      spike-triggered and non-spike-triggered distributions can be adequately
      represented using Gaussian mixtures. Because we derive the model from a
      generative perspective, its components are easy to interpret as they correspond
      to, for example, the spike-triggered distribution and the interspike interval
      distribution. The model is able to capture complex dependencies on high
      dimensional stimuli with far fewer parameters than other approaches such as
      histogram-based methods. The added flexibility comes at the cost of a non-concave
      log-likelihood. We show that in practice this does not have to be an issue and
      the mixture-based model is able to outperform generalized linear and quadratic
      models. 

PMID- 24278007
TI  - Harnessing diversity towards the reconstructing of large scale gene regulatory
      networks.
AB  - Elucidating gene regulatory network (GRN) from large scale experimental data
      remains a central challenge in systems biology. Recently, numerous techniques,
      particularly consensus driven approaches combining different algorithms, have
      become a potentially promising strategy to infer accurate GRNs. Here, we develop
      a novel consensus inference algorithm, TopkNet that can integrate multiple
      algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud
      computing framework demonstrated that (i) a simple strategy to combine many
      algorithms does not always lead to performance improvement compared to the cost
      of consensus and (ii) TopkNet integrating only high-performance algorithms
      provide significant performance improvement compared to the best individual
      algorithms and community prediction. These results suggest that a priori
      determination of high-performance algorithms is a key to reconstruct an unknown
      regulatory network. Similarity among gene-expression datasets can be useful to
      determine potential optimal algorithms for reconstruction of unknown regulatory
      networks, i.e., if expression-data associated with known regulatory network is
      similar to that with unknown regulatory network, optimal algorithms determined
      for the known regulatory network can be repurposed to infer the unknown
      regulatory network. Based on this observation, we developed a quantitative
      measure of similarity among gene-expression datasets and demonstrated that, if
      similarity between the two expression datasets is high, TopkNet integrating
      algorithms that are optimal for known dataset perform well on the unknown
      dataset. The consensus framework, TopkNet, together with the similarity measure
      proposed in this study provides a powerful strategy towards harnessing the wisdom
      of the crowds in reconstruction of unknown regulatory networks. 

PMID- 24278009
TI  - Multiscale modeling of influenza A virus infection supports the development of
      direct-acting antivirals.
AB  - Influenza A viruses are respiratory pathogens that cause seasonal epidemics with
      up to 500,000 deaths each year. Yet there are currently only two classes of
      antivirals licensed for treatment and drug-resistant strains are on the rise. A
      major challenge for the discovery of new anti-influenza agents is the
      identification of drug targets that efficiently interfere with viral replication.
      To support this step, we developed a multiscale model of influenza A virus
      infection which comprises both the intracellular level where the virus
      synthesizes its proteins, replicates its genome, and assembles new virions and
      the extracellular level where it spreads to new host cells. This integrated
      modeling approach recapitulates a wide range of experimental data across both
      scales including the time course of all three viral RNA species inside an
      infected cell and the infection dynamics in a cell population. It also allowed us
      to systematically study how interfering with specific steps of the viral life
      cycle affects virus production. We find that inhibitors of viral transcription,
      replication, protein synthesis, nuclear export, and assembly/release are most
      effective in decreasing virus titers whereas targeting virus entry primarily
      delays infection. In addition, our results suggest that for some antivirals
      therapy success strongly depends on the lifespan of infected cells and, thus, on
      the dynamics of virus-induced apoptosis or the host's immune response. Hence, the
      proposed model provides a systems-level understanding of influenza A virus
      infection and therapy as well as an ideal platform to include further levels of
      complexity toward a comprehensive description of infectious diseases. 

PMID- 24278008
TI  - Electrostatically accelerated encounter and folding for facile recognition of
      intrinsically disordered proteins.
AB  - Achieving facile specific recognition is essential for intrinsically disordered
      proteins (IDPs) that are involved in cellular signaling and regulation.
      Consideration of the physical time scales of protein folding and diffusion
      limited protein-protein encounter has suggested that the frequent requirement of
      protein folding for specific IDP recognition could lead to kinetic bottlenecks.
      How IDPs overcome such potential kinetic bottlenecks to viably function in
      signaling and regulation in general is poorly understood. Our recent
      computational and experimental study of cell-cycle regulator p27 (Ganguly et al.,
      J. Mol. Biol. (2012)) demonstrated that long-range electrostatic forces exerted
      on enriched charges of IDPs could accelerate protein-protein encounter via
      "electrostatic steering" and at the same time promote "folding-competent"
      encounter topologies to enhance the efficiency of IDP folding upon encounter.
      Here, we further investigated the coupled binding and folding mechanisms and the
      roles of electrostatic forces in the formation of three IDP complexes with more
      complex folded topologies. The surface electrostatic potentials of these
      complexes lack prominent features like those observed for the p27/Cdk2/cyclin A
      complex to directly suggest the ability of electrostatic forces to facilitate
      folding upon encounter. Nonetheless, similar electrostatically accelerated
      encounter and folding mechanisms were consistently predicted for all three
      complexes using topology-based coarse-grained simulations. Together with our
      previous analysis of charge distributions in known IDP complexes, our results
      support a prevalent role of electrostatic interactions in promoting efficient
      coupled binding and folding for facile specific recognition. These results also
      suggest that there is likely a co-evolution of IDP folded topology, charge
      characteristics, and coupled binding and folding mechanisms, driven at least
      partially by the need to achieve fast association kinetics for cellular signaling
      and regulation. 

PMID- 24278010
TI  - Conserved substitution patterns around nucleosome footprints in eukaryotes and
      Archaea derive from frequent nucleosome repositioning through evolution.
AB  - Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested
      to influence the evolution of eukaryotic genomes, both by altering the propensity
      of DNA to mutate and by selection acting to maintain or exclude nucleosomes in
      particular locations. Contrary to the popular idea that nucleosomes are unique to
      eukaryotes, histone proteins have also been discovered in some archaeal genomes.
      Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in
      many respects, including their assembly into tetramers (rather than octamers)
      from histone proteins that lack N- and C-terminal tails. Here, we show that
      despite these fundamental differences the association between nucleosome
      footprints and sequence evolution is strikingly conserved between humans and the
      model archaeon Haloferax volcanii. In light of this finding we examine whether
      selection or mutation can explain concordant substitution patterns in the two
      kingdoms. Unexpectedly, we find that neither the mutation nor the selection model
      are sufficient to explain the observed association between nucleosomes and
      sequence divergence. Instead, we demonstrate that nucleosome-associated
      substitution patterns are more consistent with a third model where sequence
      divergence results in frequent repositioning of nucleosomes during evolution.
      Indeed, we show that nucleosome repositioning is both necessary and largely
      sufficient to explain the association between current nucleosome positions and
      biased substitution patterns. This finding highlights the importance of
      considering the direction of causality between genetic and epigenetic change. 

PMID- 24278012
TI  - Colonization resistance: battle of the bugs or Menage a Trois with the host?

PMID- 24278013
TI  - Disease to dirt: the biology of microbial amyloids.

PMID- 24278014
TI  - Fungal immune evasion in a model host-pathogen interaction: Candida albicans
      versus macrophages.

PMID- 24278015
TI  - A unique SUMO-2-interacting motif within LANA is essential for KSHV latency.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) stabilizes hypoxia-inducible
      factor alpha (HIF-1alpha) during latent infection, and HIF-1alpha reactivates
      lytic replication under hypoxic stress. However, the mechanism utilized by KSHV
      to block lytic reactivation with the accumulation of HIF-1alpha in latency
      remains unclear. Here, we report that LANA encoded by KSHV contains a unique SUMO
      interacting motif (LANA(SIM)) which is specific for interaction with SUMO-2 and
      facilitates LANA SUMOylation at lysine 1140. Proteomic and co-immunoprecipitation
      analysis further reveal that the SUMO-2 modified transcription repressor KAP1 is
      a critical factor recruited by LANA(SIM). Deletion of LANA(SIM) led to functional
      loss of both LANA-mediated viral episome maintenance and lytic gene silencing.
      Moreover, hypoxia reduced KAP1 SUMOylation and resulted in dissociation of both
      KAP1 and Sin3A repressors from LANA(SIM)-associated complex. Therefore, the
      LANA(SIM) motif plays an essential role in KSHV latency and is a potential drug
      target against KSHV-associated cancers. 

PMID- 24278016
TI  - The effects of somatic hypermutation on neutralization and binding in the PGT121
      family of broadly neutralizing HIV antibodies.
AB  - Broadly neutralizing HIV antibodies (bnAbs) are typically highly somatically
      mutated, raising doubts as to whether they can be elicited by vaccination. We
      used 454 sequencing and designed a novel phylogenetic method to model lineage
      evolution of the bnAbs PGT121-134 and found a positive correlation between the
      level of somatic hypermutation (SHM) and the development of neutralization
      breadth and potency. Strikingly, putative intermediates were characterized that
      show approximately half the mutation level of PGT121-134 but were still capable
      of neutralizing roughly 40-80% of PGT121-134 sensitive viruses in a 74-virus
      panel at median titers between 15- and 3-fold higher than PGT121-134. Such
      antibodies with lower levels of SHM may be more amenable to elicitation through
      vaccination while still providing noteworthy coverage. Binding characterization
      indicated a preference of inferred intermediates for native Env binding over
      monomeric gp120, suggesting that the PGT121-134 lineage may have been selected
      for binding to native Env at some point during maturation. Analysis of glycan
      dependent neutralization for inferred intermediates identified additional
      adjacent glycans that comprise the epitope and suggests changes in glycan
      dependency or recognition over the course of affinity maturation for this
      lineage. Finally, patterns of neutralization of inferred bnAb intermediates
      suggest hypotheses as to how SHM may lead to potent and broad HIV neutralization
      and provide important clues for immunogen design. 

PMID- 24278017
TI  - A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the
      mosquito midgut.
AB  - Malaria transmission-blocking (T-B) interventions are essential for malaria
      elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst
      transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony,
      represent one approach to achieving this goal. Chondroitin sulfate
      glycosaminoglycans (CS-GAGs) on the Anopheles gambiae midgut surface are putative
      ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic
      polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS
      GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut
      oocyst development by as much as 99% (P<0.0001) in mosquitoes fed with P.
      falciparum and Plasmodium berghei. Through direct-binding assays, we observed
      that VS1 bound to two critical ookinete micronemal proteins, each containing at
      least one von Willebrand factor A (vWA) domain: (i) circumsporozoite protein and
      thrombospondin-related anonymous protein-related protein (CTRP) and (ii) vWA
      domain-related protein (WARP). By immunofluorescence microscopy, we observed that
      VS1 stains permeabilized P. falciparum and P. berghei ookinetes but does not
      stain P. berghei CTRP knockouts or transgenic parasites lacking the vWA domains
      of CTRP while retaining the thrombospondin repeat region. We produced structural
      homology models of the first vWA domain of CTRP and identified, as expected,
      putative GAG-binding sites on CTRP that align closely with those predicted for
      the human vWA A1 domain and the Toxoplasma gondii MIC2 adhesin. Importantly, the
      models also identified patches of electropositive residues that may extend CTRP's
      GAG-binding motif and thus potentiate VS1 binding. Our molecule binds to a
      critical, conserved ookinete protein, CTRP, and exhibits potent malaria T-B
      activity. This study lays the framework for a high-throughput screen of existing
      libraries of safe compounds to identify those with potent T-B activity. We
      envision that such compounds when used as partner drugs with current antimalarial
      regimens and with RTS,S vaccine delivery could prevent the transmission of drug
      resistant and vaccine-breakthrough strains. 

PMID- 24278018
TI  - Unraveling a three-step spatiotemporal mechanism of triggering of receptor
      induced Nipah virus fusion and cell entry.
AB  - Membrane fusion is essential for entry of the biomedically-important
      paramyxoviruses into their host cells (viral-cell fusion), and for syncytia
      formation (cell-cell fusion), often induced by paramyxoviral infections [e.g.
      those of the deadly Nipah virus (NiV)]. For most paramyxoviruses, membrane fusion
      requires two viral glycoproteins. Upon receptor binding, the attachment
      glycoprotein (HN/H/G) triggers the fusion glycoprotein (F) to undergo
      conformational changes that merge viral and/or cell membranes. However, a
      significant knowledge gap remains on how HN/H/G couples cell receptor binding to
      F-triggering. Via interdisciplinary approaches we report the first comprehensive
      mechanism of NiV membrane fusion triggering, involving three spatiotemporally
      sequential cell receptor-induced conformational steps in NiV-G: two in the head
      and one in the stalk. Interestingly, a headless NiV-G mutant was able to trigger
      NiV-F, and the two head conformational steps were required for the exposure of
      the stalk domain. Moreover, the headless NiV-G prematurely triggered NiV-F on
      virions, indicating that the NiV-G head prevents premature triggering of NiV-F on
      virions by concealing a F-triggering stalk domain until the correct time and
      place: receptor-binding. Based on these and recent paramyxovirus findings, we
      present a comprehensive and fundamentally conserved mechanistic model of
      paramyxovirus membrane fusion triggering and cell entry. 

PMID- 24278019
TI  - Haploid genetic screens identify an essential role for PLP2 in the downregulation
      of novel plasma membrane targets by viral E3 ubiquitin ligases.
AB  - The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral
      ubiquitin E3 ligases which downregulate MHC-I and additional cell surface
      immunoreceptors. To identify novel cellular genes required for K5 function we
      performed a forward genetic screen in near-haploid human KBM7 cells. The screen
      identified proteolipid protein 2 (PLP2), a MARVEL domain protein of unknown
      function, as essential for K5 activity. Genetic loss of PLP2 traps the viral
      ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and
      degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5
      expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range
      of novel K5 targets, all of which required PLP2 for their K5-mediated
      downregulation. This work ascribes a critical function to PLP2 for viral ligase
      activity and underlines the power of non-lethal haploid genetic screens in human
      cells to identify the genes involved in pathogen manipulation of the host immune
      system. 

PMID- 24278020
TI  - Type I and type III interferons drive redundant amplification loops to induce a
      transcriptional signature in influenza-infected airway epithelia.
AB  - Interferons (IFNs) are a group of cytokines with a well-established antiviral
      function. They can be induced by viral infection, are secreted and bind to
      specific receptors on the same or neighbouring cells to activate the expression
      of hundreds of IFN stimulated genes (ISGs) with antiviral function. Type I IFN
      has been known for more than half a century. However, more recently, type III IFN
      (IFNlambda, IL-28/29) was shown to play a similar role and to be particularly
      important at epithelial surfaces. Here we show that airway epithelia, the primary
      target of influenza A virus, produce both IFN I and III upon infection, and that
      induction of both depends on the RIG-I/MAVS pathway. While IRF3 is generally
      regarded as the transcription factor required for initiation of IFN transcription
      and the so-called "priming loop", we find that IRF3 deficiency has little impact
      on IFN expression. In contrast, lack of IRF7 reduced IFN production
      significantly, and only IRF3(-/-)IRF7(-/-) double deficiency completely abolished
      it. The transcriptional response to influenza infection was largely dependent on
      IFNs, as it was reduced to a few upregulated genes in epithelia lacking receptors
      for both type I and III IFN (IFNAR1(-/-)IL-28Ralpha(-/-)). Wild-type epithelia
      and epithelia deficient in either the type I IFN receptor or the type III IFN
      receptor exhibit similar transcriptional profiles in response to virus,
      indicating that none of the induced genes depends selectively on only one IFN
      system. In chimeric mice, the lack of both IFN I and III signalling in the
      stromal compartment alone significantly increased the susceptibility to influenza
      infection. In conclusion, virus infection of airway epithelia induces, via a RIG
      I/MAVS/IRF7 dependent pathway, both type I and III IFNs which drive two
      completely overlapping and redundant amplification loops to upregulate ISGs and
      protect from influenza infection. 

PMID- 24278021
TI  - SPOC1-mediated antiviral host cell response is antagonized early in human
      adenovirus type 5 infection.
AB  - Little is known about immediate phases after viral infection and how an incoming
      viral genome complex counteracts host cell defenses, before the start of viral
      gene expression. Adenovirus (Ad) serves as an ideal model, since entry and onset
      of gene expression are rapid and highly efficient, and mechanisms used 24-48
      hours post infection to counteract host antiviral and DNA repair factors (e.g.
      p53, Mre11, Daxx) are well studied. Here, we identify an even earlier host cell
      target for Ad, the chromatin-associated factor and epigenetic reader, SPOC1,
      recently found recruited to double strand breaks, and playing a role in DNA
      damage response. SPOC1 co-localized with viral replication centers in the host
      cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the
      transcriptional level. We discovered that this SPOC1-mediated restriction imposed
      upon Ad growth is relieved by its functional association with the Ad major core
      protein pVII that enters with the viral genome, followed by E1B-55K/E4orf6
      dependent proteasomal degradation of SPOC1. Mimicking removal of SPOC1 in the
      cell, knock down of this cellular restriction factor using RNAi techniques
      resulted in significantly increased Ad replication, including enhanced viral gene
      expression. However, depletion of SPOC1 also reduced the efficiency of E1B-55K
      transcriptional repression of cellular promoters, with possible implications for
      viral transformation. Intriguingly, not exclusive to Ad infection, other human
      pathogenic viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected
      cells. Our findings provide a general model for how pathogenic human viruses
      antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A
      better understanding of viral entry and early restrictive functions in host cells
      should provide new perspectives for developing antiviral agents and therapies.
      Conversely, for Ad vectors used in gene therapy, counteracting mechanisms
      eradicating incoming viral DNA would increase Ad vector efficacy and safety for
      the patient. 

PMID- 24278022
TI  - The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV
      1) transcytosis across epithelial cells.
AB  - The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses
      mucosal surfaces to establish infection are unknown. Acidic genital secretions of
      HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the
      combination of acidic pH and Env-specific IgG, including that from cervicovaginal
      and seminal fluids of HIV-1-infected individuals, augmented transcytosis across
      epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH
      or non-specific IgG at either pH. Enhanced transcytosis was observed with
      clinical HIV-1 isolates, including transmitted/founder strains, and was
      eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non
      neutralizing antibodies allowed similar or less transcytosis than neutralizing
      antibodies. However, the ratio of total:infectious virus was higher for
      neutralizing antibodies, indicating that they allowed transcytosis while blocking
      infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn
      expression in columnar epithelia lining the human endocervix and penile urethra.
      Acidity and Env-specific IgG enhance transcytosis of virus across epithelial
      cells via FcRn and could facilitate translocation of virus to susceptible target
      cells following sexual exposure. 

PMID- 24278023
TI  - Brd4 is displaced from HPV replication factories as they expand and amplify viral
      DNA.
AB  - Replication foci are generated by many viruses to concentrate and localize viral
      DNA synthesis to specific regions of the cell. Expression of the HPV16 E1 and E2
      replication proteins in keratinocytes results in nuclear foci that recruit
      proteins associated with the host DNA damage response. We show that the Brd4
      protein localizes to these foci and is essential for their formation. However,
      when E1 and E2 begin amplifying viral DNA, Brd4 is displaced from the foci and
      cellular factors associated with DNA synthesis and homologous recombination are
      recruited. Differentiated HPV-infected keratinocytes form similar nuclear foci
      that contain amplifying viral DNA. We compare the different foci and show that,
      while they have many characteristics in common, there is a switch between early
      Brd4-dependent foci and mature Brd4-independent replication foci. However, HPV
      genomes encoding mutated E2 proteins that are unable to bind Brd4 can replicate
      and amplify the viral genome. We propose that, while E1, E2 and Brd4 might bind
      host chromatin at early stages of infection, there is a temporal and functional
      switch at later stages and increased E1 and E2 levels promote viral DNA
      amplification, displacement of Brd4 and growth of a replication factory. The
      concomitant DNA damage response recruits proteins required for DNA synthesis and
      repair, which could then be utilized for viral DNA replication. Hence, while Brd4
      can enhance replication by concentrating viral processes in specific regions of
      the host nucleus, this interaction is not absolutely essential for HPV
      replication. 

PMID- 24278024
TI  - Mode of parainfluenza virus transmission determines the dynamics of primary
      infection and protection from reinfection.
AB  - Little is known about how the mode of respiratory virus transmission determines
      the dynamics of primary infection and protection from reinfection. Using non
      invasive imaging of murine parainfluenza virus 1 (Sendai virus) in living mice,
      we determined the frequency, timing, dynamics, and virulence of primary infection
      after contact and airborne transmission, as well as the tropism and magnitude of
      reinfection after subsequent challenge. Contact transmission of Sendai virus was
      100% efficient, phenotypically uniform, initiated and grew to robust levels in
      the upper respiratory tract (URT), later spread to the lungs, grew to a lower
      level in the lungs than the URT, and protected from reinfection completely in the
      URT yet only partially in the lungs. Airborne transmission through 7.6-cm and
      15.2-cm separations between donor and recipient mice was 86%-100% efficient. The
      dynamics of primary infection after airborne transmission varied between
      individual mice and included the following categories: (a) non-productive
      transmission, (b) tracheal dominant, (c) tracheal initiated yet respiratory
      disseminated, and (d) nasopharyngeal initiated yet respiratory disseminated. Any
      previous exposure to Sendai virus infection protected from mortality and severe
      morbidity after lethal challenge. Furthermore, a higher level of primary
      infection in a given respiratory tissue (nasopharynx, trachea, or lungs) was
      inversely correlated with the level of reinfection in that same tissue. Overall,
      the mode of transmission determined the dynamics and tropism of primary
      infection, which in turn governed the level of seroconversion and protection from
      reinfection. These data are the first description of the dynamics of respiratory
      virus infection and protection from reinfection throughout the respiratory tracts
      of living animals after airborne transmission. This work provides a basis for
      understanding parainfluenza virus transmission and protective immunity and for
      developing novel vaccines and non-pharmaceutical interventions. 

PMID- 24278025
TI  - Killer bee molecules: antimicrobial peptides as effector molecules to target
      sporogonic stages of Plasmodium.
AB  - A new generation of strategies is evolving that aim to block malaria transmission
      by employing genetically modified vectors or mosquito pathogens or symbionts that
      express anti-parasite molecules. Whilst transgenic technologies have advanced
      rapidly, there is still a paucity of effector molecules with potent anti-malaria
      activity whose expression does not cause detrimental effects on mosquito fitness.
      Our objective was to examine a wide range of antimicrobial peptides (AMPs) for
      their toxic effects on Plasmodium and anopheline mosquitoes. Specifically
      targeting early sporogonic stages, we initially screened AMPs for toxicity
      against a mosquito cell line and P. berghei ookinetes. Promising candidate AMPs
      were fed to mosquitoes to monitor adverse fitness effects, and their efficacy in
      blocking rodent malaria infection in Anopheles stephensi was assessed. This was
      followed by tests to determine their activity against P. falciparum in An.
      gambiae, initially using laboratory cultures to infect mosquitoes, then
      culminating in preliminary assays in the field using gametocytes and mosquitoes
      collected from the same area in Mali, West Africa. From a range of 33 molecules,
      six AMPs able to block Plasmodium development were identified: Anoplin,
      Duramycin, Mastoparan X, Melittin, TP10 and Vida3. With the exception of Anoplin
      and Mastoparan X, these AMPs were also toxic to an An. gambiae cell line at a
      concentration of 25 uM. However, when tested in mosquito blood feeds, they did
      not reduce mosquito longevity or egg production at concentrations of 50 uM.
      Peptides effective against cultured ookinetes were less effective when tested in
      vivo and differences in efficacy against P. berghei and P. falciparum were seen.
      From the range of molecules tested, the majority of effective AMPs were derived
      from bee/wasp venoms. 

PMID- 24278026
TI  - Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates
      placental defects in females.
AB  - The maintenance of key germline derived DNA methylation patterns during
      preimplantation development depends on stores of DNA cytosine methyltransferase
      1o (DNMT1o) provided by the oocyte. Dnmt1o(mat-/-) mouse embryos born to
      Dnmt1(Delta1o/Delta1o) female mice lack DNMT1o protein and have disrupted genomic
      imprinting and associated phenotypic abnormalities. Here, we describe additional
      female-specific morphological abnormalities and DNA hypomethylation defects
      outside imprinted loci, restricted to extraembryonic tissue. Compared to male
      offspring, the placentae of female offspring of Dnmt1(Delta1o/Delta1o) mothers
      displayed a higher incidence of genic and intergenic hypomethylation and more
      frequent and extreme placental dysmorphology. The majority of the affected loci
      were concentrated on the X chromosome and associated with aberrant biallelic
      expression, indicating that imprinted X-inactivation was perturbed.
      Hypomethylation of a key regulatory region of Xite within the X-inactivation
      center was present in female blastocysts shortly after the absence of methylation
      maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental
      DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence
      of additional roles beyond the maintenance of genomic imprints for DNA
      methylation events in the preimplantation embryo, including a role in imprinted X
      chromosome inactivation. 

PMID- 24278028
TI  - MYB97, MYB101 and MYB120 function as male factors that control pollen tube
      synergid interaction in Arabidopsis thaliana fertilization.
AB  - Pollen tube reception involves a pollen tube-synergid interaction that controls
      the discharge of sperm cells into the embryo sac during plant fertilization.
      Despite its importance in the sexual reproduction of plants, little is known
      about the role of gene regulation in this process. We report here that the pollen
      expressed transcription factors MYB97, MYB101 and MYB120 probably control genes
      whose encoded proteins play important roles in Arabidopsis thaliana pollen tube
      reception. They share a high amino acid sequence identity and are expressed
      mainly in mature pollen grains and pollen tubes. None of the single or double
      mutants of these three genes exhibited any visible defective phenotype. Although
      the myb97 myb101 myb120 triple mutant was not defective in pollen development,
      pollen germination, pollen tube growth or tube guidance, the pollen tubes of the
      triple mutants exhibited uncontrolled growth and failed to discharge their sperm
      cells after entering the embryo sac. In addition, the myb97 myb101 myb120 triple
      mutation significantly affected the expression of a group of pollen-expressed
      genes in mature pollen grains. All these results indicate that MYB97, MYB101 and
      MYB120 participate in pollen tube reception, possibly by controlling the
      expression of downstream genes. 

PMID- 24278027
TI  - Fine-mapping the genetic association of the major histocompatibility complex in
      multiple sclerosis: HLA and non-HLA effects.
AB  - The major histocompatibility complex (MHC) region is strongly associated with
      multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect,
      and several other alleles have been reported at different levels of validation.
      Using SNP data from genome-wide studies, we imputed and tested classical alleles
      and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes
      in 5,091 cases and 9,595 controls. We identified 11 statistically independent
      effects overall: 6 HLA-DRB1 and one DPB1 alleles in class II, one HLA-A and two B
      alleles in class I, and one signal in a region spanning from MICB to LST1. This
      genomic segment does not contain any HLA class I or II genes and provides robust
      evidence for the involvement of a non-HLA risk allele within the MHC.
      Interestingly, this region contains the TNF gene, the cognate ligand of the well
      validated TNFRSF1A MS susceptibility gene. The classical HLA effects can be
      explained to some extent by polymorphic amino acid positions in the peptide
      binding grooves. This study dissects the independent effects in the MHC, a
      critical region for MS susceptibility that harbors multiple risk alleles. 

PMID- 24278029
TI  - Pathways-driven sparse regression identifies pathways and genes associated with
      high-density lipoprotein cholesterol in two Asian cohorts.
AB  - Standard approaches to data analysis in genome-wide association studies (GWAS)
      ignore any potential functional relationships between gene variants. In contrast
      gene pathways analysis uses prior information on functional structure within the
      genome to identify pathways associated with a trait of interest. In a second
      step, important single nucleotide polymorphisms (SNPs) or genes may be identified
      within associated pathways. The pathways approach is motivated by the fact that
      genes do not act alone, but instead have effects that are likely to be mediated
      through their interaction in gene pathways. Where this is the case, pathways
      approaches may reveal aspects of a trait's genetic architecture that would
      otherwise be missed when considering SNPs in isolation. Most pathways methods
      begin by testing SNPs one at a time, and so fail to capitalise on the potential
      advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a
      dual-level, sparse regression model for the simultaneous identification of
      pathways and genes associated with a quantitative trait. Our method takes account
      of various factors specific to the joint modelling of pathways with genome-wide
      data, including widespread correlation between genetic predictors, and the fact
      that variants may overlap multiple pathways. We use a resampling strategy that
      exploits finite sample variability to provide robust rankings for pathways and
      genes. We test our method through simulation, and use it to perform pathways
      driven gene selection in a search for pathways and genes associated with
      variation in serum high-density lipoprotein cholesterol levels in two separate
      GWAS cohorts of Asian adults. By comparing results from both cohorts we identify
      a number of candidate pathways including those associated with cardiomyopathy,
      and T cell receptor and PPAR signalling. Highlighted genes include those
      associated with the L-type calcium channel, adenylate cyclase, integrin, laminin,
      MAPK signalling and immune function. 

PMID- 24278030
TI  - Ribosome synthesis and MAPK activity modulate ionizing radiation-induced germ
      cell apoptosis in Caenorhabditis elegans.
AB  - Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental
      biological process and is key for cellular homeostasis. In a forward genetic
      screen in C. elegans designed to identify DNA damage-response factors, we
      isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA
      synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ
      cell apoptosis. This weak apoptotic IR response could be phenocopied when
      interfering with other factors of ribosome synthesis. Surprisingly, despite their
      resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53
      response to IR and increased basal CEP-1 activity under normal growth conditions.
      In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is
      required for germ cell progression and physiological germ cell death. Ras/MAPK
      gain-of-function conditions could rescue the IR response defect in rpoa-2(op259),
      pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis
      downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA
      pol I subunit can interfere with multiple key signalling pathways. Ribosome
      synthesis and growth-factor signalling are perturbed in many cancer cells; such
      an interplay between basic cellular processes and signalling might be critical
      for how tumours evolve or respond to treatment. 

PMID- 24278032
TI  - Deletion of the murine cytochrome P450 Cyp2j locus by fused BAC-mediated
      recombination identifies a role for Cyp2j in the pulmonary vascular response to
      hypoxia.
AB  - Epoxyeicosatrienoic acids (EETs) confer vasoactive and cardioprotective
      functions. Genetic analysis of the contributions of these short-lived mediators
      to pathophysiology has been confounded to date by the allelic expansion in
      rodents of the portion of the genome syntenic to human CYP2J2, a gene encoding
      one of the principle cytochrome P450 epoxygenases responsible for the formation
      of EETs in humans. Mice have eight potentially functional genes that could direct
      the synthesis of epoxygenases with properties similar to those of CYP2J2. As an
      initial step towards understanding the role of the murine Cyp2j locus, we have
      created mice bearing a 626-kb deletion spanning the entire region syntenic to
      CYP2J2, using a combination of homologous and site-directed recombination
      strategies. A mouse strain in which the locus deletion was complemented by
      transgenic delivery of BAC sequences encoding human CYP2J2 was also created.
      Systemic and pulmonary hemodynamic measurements did not differ in wild-type,
      null, and complemented mice at baseline. However, hypoxic pulmonary
      vasoconstriction (HPV) during left mainstem bronchus occlusion was impaired and
      associated with reduced systemic oxygenation in null mice, but not in null mice
      bearing the human transgene. Administration of an epoxygenase inhibitor to wild
      type mice also impaired HPV. These findings demonstrate that Cyp2j gene products
      regulate the pulmonary vascular response to hypoxia. 

PMID- 24278031
TI  - DUX4 binding to retroelements creates promoters that are active in FSHD muscle
      and testis.
AB  - The human double-homeodomain retrogene DUX4 is expressed in the testis and
      epigenetically repressed in somatic tissues. Facioscapulohumeral muscular
      dystrophy (FSHD) is caused by mutations that decrease the epigenetic repression
      of DUX4 in somatic tissues and result in mis-expression of this transcription
      factor in skeletal muscle. DUX4 binds sites in the human genome that contain a
      double-homeobox sequence motif, including sites in unique regions of the genome
      as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on
      myoblasts transduced with DUX4 we show that DUX4 binds and activates
      transcription of mammalian apparent LTR-retrotransposons (MaLRs), endogenous
      retrovirus (ERVL and ERVK) elements, and pericentromeric satellite HSATII
      sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for
      genes, long non-coding RNAs, and antisense transcripts. Many of these novel
      transcripts are expressed in FSHD muscle cells but not control cells, and thus
      might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis,
      is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those
      in repetitive elements, show evolutionary conservation and some repeat-initiated
      transcripts are expressed in healthy testis, the normal expression site of DUX4,
      but more rarely in other somatic tissues. Testis expression patterns are known to
      have evolved rapidly in mammals, but the mechanisms behind this rapid change have
      not yet been identified: our results suggest that mobilization of MaLR and ERV
      elements during mammalian evolution altered germline gene expression patterns
      through transcriptional activation by DUX4. Our findings demonstrate a role for
      DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular
      dystrophy. 

PMID- 24278033
TI  - Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
AB  - In mammalian females, genes on one X are largely silenced by X-chromosome
      inactivation (XCI), although some "escape" XCI and are expressed from both Xs.
      Escapees can closely juxtapose X-inactivated genes and provide a tractable model
      for assessing boundary function at epigenetically regulated loci. To delimit
      sequences at an XCI boundary, we examined female mouse embryonic stem cells
      carrying X-linked BAC transgenes derived from an endogenous escape locus.
      Previously we determined that large BACs carrying escapee Kdm5c and flanking X
      inactivated transcripts are properly regulated. Here we identify two lines with
      truncated BACs that partially and completely delete the distal Kdm5c XCI
      boundary. This boundary is not required for escape, since despite integrating
      into regions that are normally X inactivated, transgenic Kdm5c escapes XCI, as
      determined by RNA FISH and by structurally adopting an active conformation that
      facilitates long-range preferential association with other escapees. Yet, XCI
      regulation is disrupted in the transgene fully lacking the distal boundary;
      integration site genes up to 350 kb downstream of the transgene now
      inappropriately escape XCI. Altogether, these results reveal two genetically
      separable XCI regulatory activities at Kdm5c. XCI escape is driven by a dominant
      element(s) retained in the shortest transgene that therefore lies within or
      upstream of the Kdm5c locus. Additionally, the distal XCI boundary normally plays
      an essential role in preventing nearby genes from escaping XCI. 

PMID- 24278034
TI  - MYB10 and MYB72 are required for growth under iron-limiting conditions.
AB  - Iron is essential for photosynthesis and is often a limiting nutrient for plant
      productivity. Plants respond to conditions of iron deficiency by increasing
      transcript abundance of key genes involved in iron homeostasis, but only a few
      regulators of these genes have been identified. Using genome-wide expression
      analysis, we searched for transcription factors that are induced within 24 hours
      after transferring plants to iron-deficient growth conditions. Out of nearly 100
      transcription factors shown to be up-regulated, we identified MYB10 and MYB72 as
      the most highly induced transcription factors. Here, we show that MYB10 and MYB72
      are functionally redundant and are required for plant survival in alkaline soil
      where iron availability is greatly restricted. myb10myb72 double mutants fail to
      induce transcript accumulation of the nicotianamine synthase gene NAS4. Both
      myb10myb72 mutants and nas4-1 mutants have reduced iron concentrations,
      chlorophyll levels, and shoot mass under iron-limiting conditions, indicating
      that these genes are essential for proper plant growth. The double myb10myb72
      mutant also showed nickel and zinc sensitivity, similar to the nas4 mutant.
      Ectopic expression of NAS4 rescues myb10myb72 plants, suggesting that loss of
      NAS4 is the primary defect in these plants and emphasizes the importance of
      nicotianamine, an iron chelator, in iron homeostasis. Overall, our results
      provide evidence that MYB10 and MYB72 act early in the iron-deficiency regulatory
      cascade to drive gene expression of NAS4 and are essential for plant survival
      under iron deficiency. 

PMID- 24278035
TI  - Genetic and functional studies implicate synaptic overgrowth and ring gland
      cAMP/PKA signaling defects in the Drosophila melanogaster neurofibromatosis-1
      growth deficiency.
AB  - Neurofibromatosis type 1 (NF1), a genetic disease that affects 1 in 3,000, is
      caused by loss of a large evolutionary conserved protein that serves as a GTPase
      Activating Protein (GAP) for Ras. Among Drosophila melanogaster Nf1 (dNf1) null
      mutant phenotypes, learning/memory deficits and reduced overall growth resemble
      human NF1 symptoms. These and other dNf1 defects are relatively insensitive to
      manipulations that reduce Ras signaling strength but are suppressed by increasing
      signaling through the 3'-5' cyclic adenosine monophosphate (cAMP) dependent
      Protein Kinase A (PKA) pathway, or phenocopied by inhibiting this pathway.
      However, whether dNf1 affects cAMP/PKA signaling directly or indirectly remains
      controversial. To shed light on this issue we screened 486 1(st) and 2(nd)
      chromosome deficiencies that uncover >80% of annotated genes for dominant
      modifiers of the dNf1 pupal size defect, identifying responsible genes in crosses
      with mutant alleles or by tissue-specific RNA interference (RNAi) knockdown.
      Validating the screen, identified suppressors include the previously implicated
      dAlk tyrosine kinase, its activating ligand jelly belly (jeb), two other genes
      involved in Ras/ERK signal transduction and several involved in cAMP/PKA
      signaling. Novel modifiers that implicate synaptic defects in the dNf1 growth
      deficiency include the intersectin-related synaptic scaffold protein Dap160 and
      the cholecystokinin receptor-related CCKLR-17D1 drosulfakinin receptor. Providing
      mechanistic clues, we show that dAlk, jeb and CCKLR-17D1 are among mutants that
      also suppress a recently identified dNf1 neuromuscular junction (NMJ) overgrowth
      phenotype and that manipulations that increase cAMP/PKA signaling in adipokinetic
      hormone (AKH)-producing cells at the base of the neuroendocrine ring gland
      restore the dNf1 growth deficiency. Finally, supporting our previous contention
      that ALK might be a therapeutic target in NF1, we report that human ALK is
      expressed in cells that give rise to NF1 tumors and that NF1 regulated
      ALK/RAS/ERK signaling appears conserved in man. 

PMID- 24278036
TI  - Translation initiation factors eIF3 and HCR1 control translation termination and
      stop codon read-through in yeast cells.
AB  - Translation is divided into initiation, elongation, termination and ribosome
      recycling. Earlier work implicated several eukaryotic initiation factors (eIFs)
      in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in
      translation termination in vivo. A substantial proportion of eIF3, HCR1 and
      eukaryotic release factor 3 (eRF3) but not eIF5 (a well-defined "initiation
      specific" binding partner of eIF3) specifically co-sediments with 80S couples
      isolated from RNase-treated heavy polysomes in an eRF1-dependent manner,
      indicating the presence of eIF3 and HCR1 on terminating ribosomes. eIF3 and HCR1
      also occur in ribosome- and RNA-free complexes with both eRFs and the recycling
      factor ABCE1/RLI1. Several eIF3 mutations reduce rates of stop codon read-through
      and genetically interact with mutant eRFs. In contrast, a slow growing deletion
      of hcr1 increases read-through and accumulates eRF3 in heavy polysomes in a
      manner suppressible by overexpressed ABCE1/RLI1. Based on these and other
      findings we propose that upon stop codon recognition, HCR1 promotes eRF3.GDP
      ejection from the post-termination complexes to allow binding of its interacting
      partner ABCE1/RLI1. Furthermore, the fact that high dosage of ABCE1/RLI1 fully
      suppresses the slow growth phenotype of hcr1Delta as well as its termination but
      not initiation defects implies that the termination function of HCR1 is more
      critical for optimal proliferation than its function in translation initiation.
      Based on these and other observations we suggest that the assignment of HCR1 as a
      bona fide eIF3 subunit should be reconsidered. Together our work characterizes
      novel roles of eIF3 and HCR1 in stop codon recognition, defining a communication
      bridge between the initiation and termination/recycling phases of translation. 

PMID- 24278037
TI  - Roles of XRCC2, RAD51B and RAD51D in RAD51-independent SSA recombination.
AB  - The repair of DNA double-strand breaks by recombination is key to the maintenance
      of genome integrity in all living organisms. Recombination can however generate
      mutations and chromosomal rearrangements, making the regulation and the choice of
      specific pathways of great importance. In addition to end-joining through non
      homologous recombination pathways, DNA breaks are repaired by two homology
      dependent pathways that can be distinguished by their dependence or not on strand
      invasion catalysed by the RAD51 recombinase. Working with the plant Arabidopsis
      thaliana, we present here an unexpected role in recombination for the Arabidopsis
      RAD51 paralogues XRCC2, RAD51B and RAD51D in the RAD51-independent single-strand
      annealing pathway. The roles of these proteins are seen in spontaneous and in DSB
      induced recombination at a tandem direct repeat recombination tester locus, both
      of which are unaffected by the absence of RAD51. Individual roles of these
      proteins are suggested by the strikingly different severities of the phenotypes
      of the individual mutants, with the xrcc2 mutant being the most affected, and
      this is confirmed by epistasis analyses using multiple knockouts. Notwithstanding
      their clearly established importance for RAD51-dependent homologous
      recombination, XRCC2, RAD51B and RAD51D thus also participate in Single-Strand
      Annealing recombination. 

PMID- 24278040
TI  - Synthesis of alpha-collagen fragments and research of their influence on the
      degree of hydration of a model of epidermis.
AB  - INTRODUCTION: In recent years the interest into areas of science, such as
      cosmetology, dermatology, pharmacology or aesthetic medicine has increased
      significantly. Scientists are more frequently looking for ingredients that affect
      the skin's condition and slow down the aging process. Practically every year, the
      scientists discover a number of new chemical substances (both natural and
      synthetic) that can be potentially used to manufacture cosmetics. AIM: To
      evaluate the influence of selected peptides derived from alpha-collagen fragments
      on the degree of hydration of a model of epidermis isolated from a pig. MATERIAL
      AND METHODS: The synthesis of selected cosmetic oligopeptides were performed
      manually, on the solid medium, using procedure of SPPS (solid phase peptide
      synthesis). Following components: aqua, carbomer, glycerine, phenonip, D
      panthenol, dimethicone and triethanolamine were used to prepare a reference
      hydrogel masks. Both the number of components and the composition of hydrogels
      have been developed individually for the purposes of this research. For this
      study the skin from a domestic pig was used. The degree of the skin hydration was
      measured with the SKINTEST plus camera, which uses the latest semiconductor
      technology. RESULTS: During the study the absorption of hydrogels with peptides
      was faster than that of the reference hydrogel mask. The combination of
      hydrophilic properties of the peptide with hydrophobic properties of Palm enabled
      receiving an amphiphilic structure. Such molecules are considered to be able to
      penetrate the corneum barrier with the greatest ease. CONCLUSIONS: The results
      showed that the modified compounds have contributed to water retention in the
      cells, thereby increasing the degree of hydration of the biological material.

PMID- 24278039
TI  - Antinuclear antibodies in rosacea patients.
AB  - INTRODUCTION: Rosacea is a common inflammatory disorder, characterized by a
      spectrum of facial manifestations. The clinical similarity to other dermatoses,
      like lupus erythematosus, might lead to misdiagnosis, particularly in patients
      with elevated antinuclear antibody titers. AIM: To assess the frequency, titer
      and specificity of antinuclear antibodies in rosacea patients and correlate these
      findings with clinical features. MATERIAL AND METHODS: The study included 101
      rosacea patients and 26 sex- and age-matched controls. Immunofluorescence
      antinuclear antibody testing was performed on HEp-2 substrates. Patients' sera
      with ANA titers of 1 : 160 or higher were evaluated by Euroline analysis.
      RESULTS: Over a half (53.5%) of rosacea patients had an ANA titer greater than or
      equal to 1 : 160. Within this group 13.86% had a titer of 1 : 320, 8.91% had a
      titer of 1 : 640, and 6.93% had a titer of 1 : 1,280 or higher. The specificity
      of these antibodies could not be identified. Elevated ANA titers were present
      more often in women (55.8%) than in men (44.15%). Only two of 26 healthy
      volunteers had elevated ANA titers. One had a titer of 1 : 160 and the other of 1
      : 320. During a two-year observation period, after the initial ANA testing, none
      of the patients with ANA titers above 1 : 640 developed an apparent autoimmune
      disorder. CONCLUSIONS: Elevated ANA titers are commonly found in rosacea
      patients, what with simultaneously existing facial erythema and photosensitivity
      might lead to misdiagnosis of lupus erythematosus. Clinicians should beware of
      these findings to avoid misdiagnosing lupus erythematosus in rosacea patients
      with elevated ANA titers.

PMID- 24278038
TI  - Whole genome, whole population sequencing reveals that loss of signaling networks
      is the major adaptive strategy in a constant environment.
AB  - Molecular signaling networks are ubiquitous across life and likely evolved to
      allow organisms to sense and respond to environmental change in dynamic
      environments. Few examples exist regarding the dispensability of signaling
      networks, and it remains unclear whether they are an essential feature of a
      highly adapted biological system. Here, we show that signaling network function
      carries a fitness cost in yeast evolving in a constant environment. We performed
      whole-genome, whole-population Illumina sequencing on replicate evolution
      experiments and find the major theme of adaptive evolution in a constant
      environment is the disruption of signaling networks responsible for regulating
      the response to environmental perturbations. Over half of all identified
      mutations occurred in three major signaling networks that regulate growth
      control: glucose signaling, Ras/cAMP/PKA and HOG. This results in a loss of
      environmental sensitivity that is reproducible across experiments. However,
      adaptive clones show reduced viability under starvation conditions, demonstrating
      an evolutionary tradeoff. These mutations are beneficial in an environment with a
      constant and predictable nutrient supply, likely because they result in
      constitutive growth, but reduce fitness in an environment where nutrient supply
      is not constant. Our results are a clear example of the myopic nature of
      evolution: a loss of environmental sensitivity in a constant environment is
      adaptive in the short term, but maladaptive should the environment change. 

PMID- 24278041
TI  - Telomere shortening in cultured human dermal fibroblasts is associated with acute
      photodamage induced by UVA irradiation.
AB  - INTRODUCTION: Photoaging is the superposition of chronic ultraviolet (UV)-induced
      damage on intrinsic aging. Telomere length is a molecular marker of cell aging,
      and genomic instability due to telomere shortening has been linked to several
      aging-related diseases. AIM: To explore the effects of different doses of
      ultraviolet A (UVA) on the length of telomeres in human skin fibroblasts and
      partly reveal the mechanism of skin photoaging initiated by UVA irradiation.
      MATERIAL AND METHODS: Primary cultured human skin fibroblasts were irradiated
      with different doses of UVA light. Cell viability, cell cycle phase, beta
      galactosidase, and the length of telomeres were assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry,
      cytochemical staining, and real-time polymerase chain reactions, respectively.
      RESULTS: After UVA irradiation, inhibited proliferation, S phase accumulation and
      increased expression of senescence-associated beta-galactosidase were observed in
      cultured fibroblasts. Moreover, the length of telomeres in UVA-treated cells was
      shortened in a dose-dependent manner as compared to controls (p < 0.05).
      CONCLUSIONS: These results suggest that telomere length in human dermal
      fibroblasts can be shortened by a single high dosage of UVA radiation, and that
      acute photodamage might contribute to early photoaging in human skin via rapid
      telomere shortening. This study potentially provides the basis for better
      understanding of the molecular mechanism of photoaging.

PMID- 24278042
TI  - Oral retinoids and rexinoids in cutaneous T-cell lymphomas.
AB  - Retinoids are biologically active derivatives of vitamin A modulating cell
      proliferation, differentiation, apoptosis and altering the immune response. They
      have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the
      exact mechanism of retinoids' action is unclear. It is based on the presence of
      specific receptors' families, mediating the biological effects of retinoids on
      the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR).
      Orally administrated bexarotene, the first synthetic selective RXR retinoid, was
      revealed to be active against the cutaneous manifestation of CTCL. The toxicity
      profile caused by bexarotene seems to be more limited to laboratory values and
      better tolerated than classical retinoids, but generally associated with more
      severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X
      receptor-mediated retinoids have modest objective response rates and, therefore,
      most likely will have limited impact as monotherapeutic agents. However, the
      immunomodulatory effects of RAR and RXR retinoids provide a rational basis for
      using retinoids in combination with other biologic immune response modifiers,
      phototherapy and radiotherapy. The authors reviewed the literature on the results
      of the use of retinoids and rexinoids in patients with mycosis fungoides and
      Sezary syndrome. 

PMID- 24278044
TI  - The role of fungi in allergic diseases.
AB  - Allergic diseases such as allergic rhinitis, pharyngitis, laryngitis, asthma,
      airborne dermatitis, or allergic conjunctivitis, can be caused or aggravated by
      components of bioaerosol from natural environment or from indoor environment in
      enclosed spaces, workplaces and homes. The main components of bioaerosol are
      fungi and their metabolites, which are common in the environment. 

PMID- 24278043
TI  - Skin melanocytes: biology and development.
AB  - In the human skin, melanocytes are present in the epidermis and hair follicles.
      The basic features of these cells are the ability to melanin production and the
      origin from neural crest cells. This last element is important because there are
      other cells able to produce melanin but of different embryonic origin (pigmented
      epithelium of retina, some neurons, adipocytes). The life cycle of melanocyte
      consists of several steps including differentiation of melanocyte lineage/s from
      neural crest, migration and proliferation of melanoblasts, differentiation of
      melanoblasts into melanocytes, proliferation and maturation of melanocytes at the
      target places (activity of melanogenic enzymes, melanosome formation and
      transport to keratinocytes) and eventual cell death (hair melanocytes).
      Melanocytes of the epidermis and hair are cells sharing some common features but
      in general they form biologically different populations living in unique niches
      of the skin. 

PMID- 24278045
TI  - Centella asiatica in cosmetology.
AB  - Centella asiatica known as Gotu Kola is a medicinal plant that has been used in
      folk medicine for hundreds of years as well as in scientifically oriented
      medicine. The active compounds include pentacyclic triterpenes, mainly
      asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is
      effective in improving treatment of small wounds, hypertrophic wounds as well as
      burns, psoriasis and scleroderma. The mechanism of action involves promoting
      fibroblast proliferation and increasing the synthesis of collagen and
      intracellular fibronectin content and also improvement of the tensile strength of
      newly formed skin as well as inhibiting the inflammatory phase of hypertrophic
      scars and keloids. Research results indicate that it can be used in the treatment
      of photoaging skin, cellulite and striae. 

PMID- 24278046
TI  - Total skin electron irradiation techniques: a review.
AB  - Total skin electron irradiation (TSEI) has been employed as one of the methods of
      mycosis fungoides treatment since the mid-twentieth century. In order to improve
      the effects and limit the complications following radiotherapy, a number of
      varieties of the TSEI method, frequently differing in the implementation mode
      have been developed. The paper provides a systematic review of the different
      varieties of TSEI. The discussed differences concerned especially: (i)
      technological requirements and geometric conditions, (ii) the alignment of the
      patient, (iii) the number of treatment fields, and (iv) dose fractionation
      scheme. 

PMID- 24278047
TI  - Disseminated atypical molluscum contagiosum as a presenting symptom of HIV
      infection.
AB  - Atypical forms of molluscum contagiosum may be challenging to diagnose and are
      found in immunocompromised patients where they indicate severe impairment of
      cellular immunity. We report a case of disseminated atypical molluscum
      contagiosum which was the first sign of HIV infection and AIDS disease in a 38
      year-old male patient. The lesions - painless, flesh-colored and violaceous
      papules and nodules - spread systematically for previous 3 years. They were
      located on the face, forearms, in the groins and in the genital region. Serologic
      tests for HIV-1 and hepatitis C virus were positive. CD4+ T-cells count was
      80/mm(3). The skin biopsy showed intracytoplasmic molluscum bodies. Atypical,
      recalcitrant, disseminated or facial molluscum contagiosum requires immediate HIV
      testing. In our patient, both the opportunity for early diagnosis and the
      institution of effective therapy were missed. 

PMID- 24278048
TI  - Suspicion of pulmonary embolism during treatment of pemphigoid gestationis.
AB  - Pemphigoid gestationis (PG), first described in 1872 by Laws Milton, is a rare
      autoimmune bullous disease of pregnancy and puerperium. Pemphigoid gestationis
      has been estimated to occur in 1: 50 000 pregnancies and usually presents in the
      second or third trimester with exacerbation after partum. This disease is caused
      by circulating IgG1 immunoglobulin against hemidesmosomal protein bullous
      pemphigoid BP180 (BPAG2) type XVII collagen and less frequently BP230. We present
      a case of pemphigoid gestationis in primigravida with complications during
      treatment due to the suspicion of pulmonary embolism. 

PMID- 24278049
TI  - Application of native prick test in diagnosis of bed bug allergy.
AB  - The aim of the study was case report of the patient with systemic reaction after
      a bed bug (Cimex lectularius) bite. A 23-year-old female, previously healthy,
      reports systemic reaction, including rash on her corpus and limbs, itching,
      nausea, conciseness disorder, forcing her to call the ambulance. The interview
      revealed that the bed bug occurs in the patient's apartment. A prick-by-prick
      test with bed bug excretion was made. The skin test with native allergen was
      strongly positive (histamine 5 mm/5 mm, prick-by-prick 12 mm/8 mm). The prick-by
      prick test was useful in objective confirmation of the source of symptoms. 

PMID- 24278050
TI  - The development of squamous cell carcinoma in a patient after kidney
      transplantation: a case report.
AB  - In patients with organ transplantation as compared to the general population the
      risk of cancer is significantly increased. The most common changes are malignant
      tumors of the skin, constituting 30-65% of malignant tumors found in recipients.
      Potential risk factors for skin cancer after a transplant operation are: solar
      radiation, immunosuppressive therapy, genetic factors, infection with HPV and
      skin cancer transmission before transplantation. In contrast to the
      immunocompetent population, skin cancers in transplant recipients are dominated
      by squamous cell carcinoma, followed by basal cell carcinoma. Squamous cell
      carcinoma in patients after transplantation is characterized by a strong tendency
      to give local recurrences and distant metastases. Due to the high risk of
      developing skin cancer in transplant recipients, preventive oncology plays an
      important role in the long-term care of patients after transplantation. This
      includes: sun protection, education, and early treatment of patients with
      precancerous lesions. It is also stressed that systematic dermatologic studies
      need to be carried out in patients after transplantation surgery. The paper
      contains basic information about skin cancers in organ transplant recipients:
      epidemiology, potential risk factors, treatment and prognosis. The paper presents
      also a case of patient who developed squamous cell carcinoma of the skin 3 years
      after renal transplantation. 

PMID- 24278051
TI  - Serum concentrations of metalloproteinase 2, metalloproteinase 9 and granzyme B
      in contact eczema patients.
AB  - INTRODUCTION: Contact eczema is a common skin condition with complex etiology,
      variable clinical presentation and lengthy therapy duration. The mechanism of
      contact eczema is complex, since it is affected by multiple inflammatory
      mediators. AIM: To assess concentrations of metalloproteinase 2 (MMP-2),
      metalloproteinase 9 (MMP-9) and granzyme B (GzmB) in patients with contact
      eczema. MATERIAL AND METHODS: Seventy patients with contact eczema and 30 healthy
      persons as controls were included in the study. In all subjects, MMP-2, MMP-9 and
      GzmB were determined using ELISA immunoassay. In study group patients,
      concentrations were assayed in periods of disease exacerbation and remission.
      Obtained results were analyzed statistically. RESULTS: Mean MMP-2 and GzmB
      concentrations were found to be significantly higher in the study group than in
      the control group. Mean MMP-2, MMP-9 and GzmB levels were also statistically
      significantly higher during skin lesion relapse compared to contact eczema
      remission periods. CONCLUSIONS: The presented paper demonstrates that MMP-2, MMP
      9 and GzmB are good markers of contact eczema exacerbations.

PMID- 24278052
TI  - The role of focal infections in the pathogenesis of psoriasis and chronic
      urticaria.
AB  - INTRODUCTION: The Focal Infection Theory, originally presented at the beginning
      of the 20(th) century, postulates that systemic diseases can be caused by
      microorganisms that arise from the focus of infection. Foci of infections have
      been described as sinuses, adenoids, tonsils, teeth, genitourinary tract, gall
      bladder and kidneys. A focus of infection is defined as the area that can occur
      in any part of the body, contains a pathogen (microorganism) and is usually
      asymptomatic. There are discordant opinions about the role of focal infections in
      the pathogenesis of psoriasis and urticaria. AIM: To establish whether there is a
      higher incidence of focal infections in patients with chronic urticaria and
      psoriasis. MATERIAL AND METHODS: We retrospectively reviewed 129 patients with a
      history of psoriasis and chronic urticaria: 58 women and 71 men treated in the
      Department of Dermatology of the Jagiellonian University Medical College in
      Krakow. RESULTS: In the analyzed group, 11 patients had a dental consultation, 58
      - laryngological consultation and 29 women had a gynecological consultation. The
      most common examples of focal infection were tonsillitis, upper respiratory tract
      infections, sinusitis, dental caries and genitourinary tract infections.
      Aggravating factors were similar to previously described. CONCLUSIONS: A high
      incidence of focal infections in patients with psoriasis and urticaria suggests
      that infections may play a significant role in the pathogenesis of these skin
      disorders. Treatment of infection foci may play the key role in the remission of
      skin changes.

PMID- 24278053
TI  - Satisfaction with life in a group of psoriasis patients.
AB  - INTRODUCTION: Psoriasis is one of the most frequent inflammatory diseases of the
      skin, associated with an epidermal proliferation and a specific morphology of
      lesions. Patients with psoriasis perceive their appearance specifically; they are
      frequently rejected by their surroundings and perceive their quality of life as
      considerably poorer. AIM: To evaluate the satisfaction with life in patients with
      psoriasis, and to analyze the effect of this disease on the prevalence of
      depression in this group. MATERIAL AND METHODS: The study included 100 psoriasis
      vulgaris patients treated at the Voivodeship Outpatient Clinic of Skin and
      Venereal Diseases in Lomza (Poland). Sociodemographic data of the participants
      and the clinical characteristics of the disease were collected using a
      standardized questionnaire survey. The global feeling of satisfaction with life
      was evaluated with the Satisfaction with Life Scale and the Beck's Depression
      Inventory. RESULTS: Mean SWLS scores suggested that the examined patients
      experienced moderate levels of satisfaction with life (18.92 and 18.69 points in
      women and men, respectively). The life satisfaction was the highest amongst
      patients between 50 and 60 years of age (p = 0.81). The mean score of the Beck
      Depression Inventory was at a threshold of mild depression (14.08 and 13.65
      points in women and men, respectively). CONCLUSIONS: Our participants presented
      moderate levels of satisfaction with life. A lower satisfaction with life was
      associated with a poorer quality of life and a higher prevalence of depressive
      symptoms.

PMID- 24278054
TI  - Optimism as a predictor of health-related quality of life in psoriatics.
AB  - INTRODUCTION: Psoriasis is a chronic and relapsing disease which significantly
      affects the quality of life and social functioning of the affected people. It is
      one of the so-called psychodermatological diseases, which means that there exists
      a psychological component in the image of the disease. AIM: To examine the
      relationship between health-related quality of life (HRQoL) in psoriatics and
      selected demographic, medical and psychological (dispositional optimism)
      variables and to determine the predictors of HRQoL in the examined group.
      MATERIAL AND METHODS: The study consisted of 138 patients with the diagnosis of
      psoriasis vulgaris. Most respondents (125) had psoriasis on exposed parts of the
      body. METHODS USED: SKINDEX, Life Orientation Test, PASI. RESULTS: The gender
      does not differentiate patients in terms of HRQoL and optimism. Almost all of
      analyzed variables correlate with HRQoL and all examined variables explain the
      results variability for overall HRQoL but only optimism explains the highest
      percentage of the variability (beta = -0.35). CONCLUSIONS: The study demonstrated
      a very interesting relationship - the stronger optimism the better quality of
      life in psoriatics. So, a generalized expectation of positive life events is
      related to better assessment of HRQoL.

PMID- 24278055
TI  - Recurrent aphthous stomatitis: genetic aspects of etiology.
AB  - Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers - RAU; canker
      sores) is a chronic inflammatory, ulcerative condition of the oral mucosa. Its
      prevalence in the general population ranges between 5% and 20%, depending on the
      method and group studied. The etiopathogenesis of the disease is considered to be
      multifactorial, but remains still not fully understood. In patients with RAS, an
      enhanced immunologic response occurs to some trigger factors that may include:
      mechanical injury, stress or bacterial and viral antigens. Higher prevalence of
      aphthae in relatives may also indicate the genetic background of the condition.
      The inheritance of some specific gene polymorphisms, especially those encoding
      proinflammatory cytokines, which play a role in the formation of aphthous ulcer,
      may predispose family members to RAS. The purpose of this paper was to present
      the main clinical features of recurrent aphthous stomatitis, epidemiologic data
      and crucial etiopathogenetic factors with a special emphasis on genetic
      background of the condition. 

PMID- 24278056
TI  - Supplementation with long chain polyunsaturated fatty acids in treatment of
      atopic dermatitis in children.
AB  - Some recent studies indicate that unsaturated fatty acids, components of cellular
      membranes and precursors of immunomodulators, play a significant role in the
      pathogenesis of some symptoms of atopic dermatitis. Since they cannot be
      synthesized by the human body, they must be provided with nutrition as the so
      called exogenous fatty acids: linoleic (a precursor of arachidonic acid) and
      alpha-linolenic acid (a precursor of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA)). Their deficiency facilitates the development of some
      disorders, e.g. of the cardiovascular system or of the nervous system, or becomes
      the cause of intensification of ailments in their course e.g. pruritus and
      dryness in atopic dermatitis. Though clinical examinations to date confirm the
      efficacy of fatty acid supplementation in treatment of atopic dermatitis, their
      results are not explicit. 

PMID- 24278057
TI  - Sacroiliac joint pain as an important element of psoriatic arthritis diagnosis.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by the
      coexistence of arthritis with psoriasis of the skin and nails. The sacroiliac
      joints were observed in 34-78% of patients with psoriatic arthritis. Due to such
      a high prevalence of SIJ dysfunction, understanding pathophysiology of pain and
      the associated pain pattern becomes a very important aspect of PsA diagnosis. As
      far as the etiology of SI joint dysfunction is concerned, it has not been
      disambiguated yet. Among the main causative factors, injuries and strains of the
      structures surrounding the joint are noted. Joint pathology usually manifests
      itself by pain occurring within the area of the joint. The causes of pain may be
      divided into two categories: intra-articular and extra-articular. Pain caused by
      the SI joint may be nociceptive or neural in nature, whereas the pain pattern
      characteristic of the joint correlates with its innervation and is consistent
      with S2 dorsal rami. 

PMID- 24278058
TI  - Causes, symptoms and prevention of food allergy.
AB  - Currently, food allergy is considered to be one of the diseases of civilization,
      which occurs as a result of the changing conditions of life and environmental
      changes (e.g. increased popularity of cesarean delivery, excessive hygienic
      regime during the neonatal-infantile period). Based on medical statistics, it can
      be concluded that this problem will be intensified. Consumption of food is one of
      the main activities in human life. What and how one eats affects our health.
      Meals eaten regularly provide the components necessary for the energy metabolism.
      Multicultural society, travel, and new trends affect the diversity of food
      consumed. The mechanism of food allergy reaction covers all 4 types of the immune
      response of the classical division of Gell and Coombs. The percentage of the
      immune response was assessed by Chandra as follows: type I - 48%, type II - 6%,
      type III - 10%, and type IV - 18%. The article presents the risk factors for food
      allergy, most common symptoms, preventive measures and characteristics of food
      products that are potential allergens. 

PMID- 24278059
TI  - Angioneurotic edema: a rare case of hypersensitivity to metoclopramide.
AB  - The case of a 30-year-old woman who had already experienced two incidents of
      angioneurotic edema and urticaria caused by drugs during the acute
      gastroenteritis. The allergological workup revealed hypersensitivity to
      metoclopramide. This case documents that metoclopramide, a drug commonly used to
      inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic
      patient but also angioneurotic edema of the tongue and larynx as well as
      urticaria. No similar cases in the literature were found. 

PMID- 24278060
TI  - Cutaneous larva migrans syndrome: a case report.
AB  - Cutaneous larva migrans (CML) is a frequent parasitic infestation caused by
      migration of animal hookworm larvae into the human epidermis. This skin disease
      is common in warmer climates among people, who have contact with contaminated
      soil. Clinical manifestation of CML is an itchy, erythematous, linear tract,
      which appears days to even months after exposure to infested sand or soil.
      Diagnosis is established on the clinical presentation. We describe a case of CML
      acquired during a holiday in Brazil. 

PMID- 24278061
TI  - Scleromyxedema: a rare disorder and its treatment difficulties.
AB  - Scleromyxedema is a rare progressive cutaneous mucinosis, usually associated with
      a systemic involvement and paraproteinemia. Its aetiology remains unknown. The
      therapeutic options include numerous treatment modalities, however, no standard
      treatment exists as the rarity of this disease prevents the execution of
      controlled therapeutic trials. This paper reports a case of a 38-year-old male
      with progressive scleromyxedema associated with gammopathy. Initially, the
      patient was treated with prednisolone and later etretinate was added to the
      therapeutic schedule with quite good clinical improvement. However, after 6
      months of treatment, several adverse effects were observed: hypercholesterolemia,
      hypertriglyceridaemia and cataract of the right eye. The patient was consulted by
      dermatologists in Warsaw and Gdansk as well as by a haematologist. The patient
      was excluded from oncological treatment. Melphalan therapy was not recommended as
      it is associated with very toxic side effects. IVIG treatment (intravenous
      immunoglobulin) was not initiated because of financial issues. As the disease
      progressed, treatment with plasmapheresis was introduced. The patient received 4
      cycles of the therapy. It was well-tolerated by the patient and gave
      satisfactory, but temporary results. In order to obtain long-lasting improvement
      the patient was treated with IVIG (21.0 g/dose for 5 consecutive days). This
      treatment modality seems to have resulted in a more stable improvement. 

PMID- 24278062
TI  - Pityriasis lichenoides-like secondary syphilis and neurosyphilis in a HIV
      infected patient.
AB  - Papulo- and vesiculo-necrotic lesions are rare manifestations of secondary
      syphilis. Until now it has been described only in HIV-infected patients with
      advanced stages of immunosuppression. This case report describes an unusual case
      of PLEVA-like syphilis in a 33-year-old man with newly diagnosed HIV infection.
      Despite that the CD4 cells level and viral load did not indicate the advance
      stage of immunosuppression, the unusual manifestation of syphilis and
      neurosyphilis occurred. The presented case indicates the need for HIV screening
      in every patient with syphilis especially when the clinical manifestation is
      unusual. Importance of syphilis testing in every case with atypical rashes should
      be also highlighted. 

PMID- 24278063
TI  - Autologous intradermal skin tests in women with Hashimoto's thyroiditis.
AB  - INTRODUCTION: In a large proportion of patients with chronic urticaria, a
      coexisting autoimmune type of Hashimoto's thyroiditis is being diagnosed. An
      intradermal test with autologous serum has been generally considered as a
      screening procedure indicating the presence of triggering autoimmune inflammatory
      factors in the sera of patients with urticaria. These factors could be possibly
      involved in the pathogenesis of the disease. Now, it seems that in order to
      complete the screening diagnostic procedures of autoimmune component in patients
      with spontaneous chronic urticaria, intradermal tests with autologous plasma
      could be also useful. AIM: To assess skin reactivity in patients suffering from
      the autoimmune type of Hashimoto's thyroiditis with serum and plasma intradermal
      tests. MATERIAL AND METHODS: Thirty-five female patients with Hashimoto's
      thyroiditis aged 23-78 years were recruited for our study. The control group
      consisted of 20 healthy volunteers with a negative history and no signs or
      symptoms of any thyroid as well as autoimmune diseases. Intradermal tests with
      autologous plasma, serum and with 0.9% NaCl (negative control) were performed.
      RESULTS: Five patients with the autoimmune type of Hashimoto's thyroiditis
      presented positive results of the autologous serum test (14.2%) while positive
      results of the autologous plasma test were obtained in 2 cases (5.7%). It seems
      to be important that subjects with positive results of intradermal tests have not
      been treated with L-thyroxine. In the case of healthy volunteers results of our
      diagnostic procedures were negative. CONCLUSIONS: This study suggests that
      thyroid suppression by L-thyroxine can result in clinical remission of urticaria
      symptoms.

PMID- 24278064
TI  - Illness acceptance degree versus intensity of psychopathological symptoms in
      patients with psoriasis.
AB  - INTRODUCTION: Chronic inflammatory skin diseases such as psoriasis have
      undoubtedly a negative impact on the patients' quality of life. Many of them may
      face various limitations in their psychosocial lives because of symptoms
      indicating the presence of psychopathological phenomena. Mental disorders in
      patients with skin diseases occur much more frequently than in the general
      population. Studies show that a considerable percentage (30-60%) of
      dermatological patients suffers from mental disorders (depressive and anxiety
      disorders being the most common). A person's attitude towards illness, its
      acceptance, and also the recognition of its limitations may be of a great
      importance in the process of the disease control. AIM: To evaluate of the
      relationship between the illness acceptance degree, and the presence and
      intensity of psychopathological symptoms in patients with psoriasis. MATERIAL AND
      METHODS: The research was conducted on a group of 54 people (23 men and 31
      women), who were treated for psoriasis in the Department of Dermatology and
      Venereology, Medical University of Lodz and in the Department of Dermatology,
      Pediatric Dermatology and Oncology, Medical University of Lodz. The following
      research methods were used: a questionnaire prepared for the purpose of the
      research, Acceptance of Illness Scale (AIS) and Symptom Checklist (SCL-90).
      RESULTS: It was found that there was a relationship between the skin illness
      acceptance degree and intensity of psychopathological symptoms in patients with
      psoriasis (negative correlations). CONCLUSIONS: The higher the degree of illness
      acceptance is, the better mental condition of patients with psoriasis is. The
      intensity of psychopathological symptoms is also affected by the duration of
      illness, other people's attitude to the skin disease, age and education level of
      the patients examined.

PMID- 24278065
TI  - Influence of azelaic and mandelic acid peels on sebum secretion in ageing women.
AB  - INTRODUCTION: Azelaic acid and mandelic acid are superficial peels commonly
      applied in people of various age groups. As they are mild and do not cause any
      side effects, they are also often used in elderly people. AIM: To compare the
      influence of azelaic and mandelic acid peels on facial sebum secretion in mature
      women aged 49-71 years. MATERIAL AND METHODS: The level of secreted sebum was
      measured in 28 women. Eleven women were treated with azelaic acid peel and 17
      with mandelic acid peel. Each of the peels was applied five times with 2-week
      intervals. The measurements were made on the cheeks and chin with the use of
      Sebumeter SM 15 (Courage & Khazaka, Germany). The last measurement, i.e. the
      sixth one, was made 2 weeks after the treatment. RESULTS: We observed a
      significant increase in sebum secretion in the U-zone after the application of
      20% azelaic peel and 40% mandelic peel. Neither peel significantly affected sebum
      secretion in the T-zone. CONCLUSIONS: Peels with 20% azelaic acid and 40%
      mandelic acid might be considered treatments which contribute to an increase in
      sebum secretion in ageing women.

PMID- 24278066
TI  - Determination of dermatology life quality index, and serum C-reactive protein and
      plasma interleukin-6 levels in patients with chronic urticaria.
AB  - INTRODUCTION: C-reactive protein (CRP) and interleukin-6 (IL-6), which is one of
      its most important simulators, were determined in great amounts in the sera of
      patients with chronic urticaria (CU). AIM: To determine the levels of IL-6 in
      patients with urticaria, and evaluate its relationship with urticaria activity
      scores and Dermatology Life Quality Index (DLQI). MATERIAL AND METHODS: Fifty
      three patients with CU were included in the study successively by determining
      their urticaria activity scores (0-3) and DLQI (0-5). The CRP and IL-6 were
      measured by immune assay methods. Thirty-two healthy subjects were included as a
      control group. RESULTS: Serum levels of IL-6 and CRP were significantly higher in
      patients with CU compared to healthy controls (p < 0.001, p = 0.026
      respectively). There was a statistically significant correlation among urticaria
      activity scores and IL-6 and CRP concentration (p = 0.004, p = 0.042). This
      correlation was more significant in patients who had moderate and severe disease
      activity scores than in those who had mild disease activity score (p < 0.001, p <
      0.001, respectively). There was a statistically significant association between
      DLQI and IL-6 (p = 0.025). This correlation was very significant in patients who
      had severe and very severe disease activity scores (p < 0.001, p < 0.001,
      respectively). DLQI scores and serum levels of IL-6 were significantly different
      in the very severe group compared to healthy controls (p = 0.024). CONCLUSIONS:
      The levels of CRP and IL-6 are increased in patients with CU. A relationship of
      DLQI and urticaria activity scores with CRP and IL-6 was found. These findings
      support the relationship between the inflammatory process in CU and the clinical
      findings.

PMID- 24278067
TI  - Cost-utility analysis of Ruconest((r)) (conestat alfa) compared to Berinert((r))
      P (human C1 esterase inhibitor) in the treatment of acute, life-threatening
      angioedema attacks in patients with hereditary angioedema.
AB  - INTRODUCTION: Administration of human C1 esterase inhibitor (Berinert((r)) P)
      from target import is the most widespread treatment strategy for patients with
      hereditary angioedema (HAE). However, a therapeutic health program including
      Ruconest((r)) (conestat alfa) could shorten a patient's expectancy for a life
      saving treatment. AIM: To evaluate the cost-utility of Ruconest((r)) (conestat
      alfa) financed from public funds within the newly introduced therapeutic health
      program compared with Berinert((r)) P (human C1 esterase inhibitor) in the
      treatment of acute angioedema attacks in adults with HAE. MATERIAL AND METHODS:
      The cost-utility analysis from the Polish healthcare payer's perspective was
      performed for 1 year (2012). The costs and health outcomes were simulated for
      three pairs of eligible HAE patient groups (active treatment and corresponding
      placebo). The incremental costs of each intervention compared with placebo were
      listed together (direct or indirect comparisons between options were impossible
      due to limited clinical data available). RESULTS: The incremental cost-utility
      ratios (ICURs) for the evaluated interventions compared with placebo were as
      follows: EUR 15,226 per QALY (Ruconest((r))) and EUR 27,786 per QALY
      (Berinert((r)) P). The probability of cost-utility (ICUR < EUR 24,279 per QALY)
      assessed for Ruconest((r)) administered in the case of acute angioedema attack
      was 61% and 41% for Berinert((r)) P. CONCLUSIONS: The administration of
      Ruconest((r)) in acute life-threatening angioedema attacks is economically
      justified from the Polish healthcare payer's perspective, results in lower costs
      and is characterized by higher cost-utility probability compared with
      Berinert((r)) P.

PMID- 24278068
TI  - A standard picture of healthy oral mucosae by direct oral microscopy.
AB  - INTRODUCTION: Direct oral microscopy constitutes a novel technique of in vivo
      oral mucosae examination. The basic principles of this method derive from
      colposcopy and dermoscopy. The main goal of direct oral microscopy is the
      earliest possible detection of oral precancerous lesions in order to implement
      their treatment as quickly as possible and prevent malignant transformation. AIM:
      To establish a standard picture of healthy oral mucosae with direct oral
      microscopy applying standard colposcopic criteria in order to create a reference
      point for further diagnosis of precancerous lesions. MATERIAL AND METHODS: Thirty
      patients of both genders with clinically unaltered oral mucosae were examined.
      For every individual, clinical examination with the naked eye was performed,
      followed by direct oral microscopy with colposcopic assessment criteria. Oral
      mucosae at various sites (lip, cheek, floor of mouth, ventral and lateral sides
      of the tongue, alveolar ridge and soft palate) were examined. RESULTS:
      Subepithelial blood vessel patterns, mucosal surface, colour tone and
      transparency were described for healthy oral mucosae. Moreover, cases with
      clinically unaltered oral mucosae where direct oral microscopy revealed
      subclinical alterations were described. CONCLUSIONS: Direct oral microscopy with
      colposcopic assessment criteria enables establishment of a repeated picture of
      unaltered oral mucosae. The standard picture of healthy oral mucosae is an
      essential reference point for application of this technique to early diagnose
      potentially malignant oral mucosal lesions as well as apply their early
      treatment.

PMID- 24278069
TI  - Topical calcineurin inhibitors in dermatology. Part I: Properties, method and
      effectiveness of drug use.
AB  - Topical calcineurin inhibitors (TCI) are a relatively new class of drugs used in
      dermatology. There are two drug forms available - tacrolimus 0.03% or 0.1%
      ointment and 1.0% pimecrolimus cream. The drugs act by inhibiting synthesis of
      proinflammatory cytokines. The only approved indication for using TCI is
      treatment of atopic dermatitis. The TCI may be used as an alternative therapy to
      corticosteroids. Tacrolimus is used to treat moderate-to-severe atopic
      dermatitis, pimecrolimus - mild-to-moderate atopic dermatitis. Topical
      calcineurin inhibitors do not cause skin atrophy and the drug absorption through
      the skin is minimal. The TCI have been well-studied, their efficacy was evaluated
      in a number of vast, long-term studies. The anti-inflammatory potency of
      tacrolimus ointment is similar to a corticosteroid with moderate activity, while
      the latter is clearly more active than pimecrolimus cream. Topical calcineurin
      inhibitors significantly relieve pruritus in atopic eczema. 

PMID- 24278070
TI  - Medicinal plants used in treatment of inflammatory skin diseases.
AB  - Skin is an organ providing contact with the environment and protecting the human
      body from unfavourable external factors. Skin inflammation, reflected adversely
      in its functioning and appearance, also unfavourably affects the psyche, the
      condition of which is important during treatment of chronic skin diseases. The
      use of plants in treatment of inflammatory skin diseases results from their
      influence on different stages of inflammation. The paper presents results of the
      study regarding the anti-inflammatory activity of the plant raw material related
      to its influence on skin. The mechanism of action, therapeutic indications and
      side effects of medicinal plants used for treatment of inflammatory diseases of
      the skin are described. 

PMID- 24278071
TI  - Dermatological problems of the puberty.
AB  - Puberty is a period of life between childhood and adulthood. It is characterized
      by many changes in morphology and appearance of the body (biological maturation),
      in the psyche - development of personality (psychological maturation), and in the
      attitude towards one's own and the opposite sex (psychosexual maturation), and in
      the social role (social maturation). Dermatological problems of adolescence are
      mainly related to fluctuations in hormone levels, mainly androgens. They include
      acne, hair problems and excessive sweating. Acne vulgaris is the most frequently
      diagnosed dermatosis in patients aged between 11 and 30 years. It is believed
      that it affects about 80% of persons in this age group or even, taking into
      account lesions of low intensity, 100% of young people. Excessive sweating is a
      condition characterised by excessive production of sweat, resulting from high
      activity of sweat glands. The sweat glands are localised in almost all areas of
      the body surface but on the hands, feet, armpits and around the groin they are
      found at the highest density. Seborrhoeic dermatitis of the scalp is a chronic,
      relapsing, inflammatory dermatosis, which currently affects about 5% of the
      population. It affects mostly young people, particularly men. 

PMID- 24278072
TI  - Pyoderma gangrenosum in a patient with common variable primary immunodeficiency.
AB  - Pyoderma gangrenosum is a rare inflammatory skin condition that is associated
      with systemic inflammatory diseases. It is characterised by the presence of well
      secluded, painful ulcerations, often located on the lower limbs. Similarly as in
      the case of acne inversa, patients' markers of the inflammatory process are
      elevated; including OB, C-reactive protein and leukocytosis. The aetiology takes
      into account an over-reactive inflammatory response to various factors (presence
      of the so-called pathergy symptom). Common variable primary immunodeficiency
      (CVID) is a disease that is rather often recognized and affects about 1/10,000
      100,000 individuals. It is a heterogeneous group of disorders of combined B-and T
      cell dysfunction. The case is described of a 22-year-old man with pyoderma
      gangrenosum that coexisted with CVID. 

PMID- 24278073
TI  - Anaphylaxis after accidental ingestion of kiwi fruit.
AB  - Numerous cases of anaphylaxis after ingestion of kiwi fruit, after the skin tests
      and during oral immunotherapy were described. The article describes the case of
      severe anaphylactic reaction that occurred in a 55-year-old patient after
      accidental ingestion of kiwi. Allergy to kiwi fruit was confirmed by a native
      test with fresh kiwi fruit. After the test, the patient experienced generalized
      organ response in the form of headache, general weakness and rashes on the neck
      and breast, and dyspnea. The patient had significantly elevated levels of total
      IgE and IgE specific to kiwi fruit. 

PMID- 24278074
TI  - Acneiform rash during lung cancer therapy with erlotinib (Tarceva((r))).
AB  - Tyrosine kinase inhibitors are currently applied in the treatment of non-small
      cell lung cancer with overexpressed epidermal growth factor receptor (EGFR).
      Acneiform rash is the earliest and most characteristic side effect of EGFR
      inhibition. The incidence may be as high as 50-100% of cases. We report a case of
      a 47-year-old patient who developed acneiform rash after 1.5 weeks of treatment
      with erlotinib. 

PMID- 24278075
TI  - Hereditary haemorrhagic telangiectasia in a patient taking anticoagulant drugs
      who has sustained facial trauma.
AB  - The authors present the case of a 41-year-old patient with hereditary hemorrhagic
      telangiectasia (HHT), who in the past had an aortic valve replacement surgery,
      currently takes anticoagulant drugs and has sustained an extensive trauma to the
      nose as a result of a dog bite. The HHT is diagnosed basing on the presence of at
      least three out of four symptoms or signs: spontaneous epistaxis, vascular
      lesions in the internal organs, skin telangiectasias and a family history of the
      disease. The presented patient showed hepatic angioma, history of recurrent
      bleeding from the tongue and spontaneous epistaxis as well as numerous skin
      telangiectasias. In his case, HHT coincided with chronic treatment with
      coagulants implemented after an implantation of the artificial aortic replacement
      valve, what substantially modified the clinical picture and course of treatment. 

PMID- 24278076
TI  - Current standards for diagnosis and treatment of syphilis: selection of some
      practical issues, based on the European (IUSTI) and U.S. (CDC) guidelines.
AB  - Syphilis continues to be an important epidemiologic problem. For a few years a
      steady increase in the incidence of this sexually transmitted disease has been
      observed. Advances in medical science obligate the doctor to use only such
      diagnostic and therapeutic approaches that are scientifically proven. Based on
      the European (IUSTI) and U.S. (CDC) guidelines, in this manuscript, we present
      some selected practical issues concerning diagnosis and treatment of syphilis. We
      truly hope that the present review will help all doctors taking care of
      syphilitic patients to systematize the current knowledge. 

PMID- 24278077
TI  - Genetic polymorphisms of CYP2D6 oxidation in patients with autoimmune bullous
      diseases.
AB  - INTRODUCTION: Bullous skin diseases, which include, among others pemphigoid,
      pemphigus, and dermatitis herpetiformis are classified as severe autoimmune
      dermatoses. It has been shown that a pattern of xenobiotic metabolism may play a
      role in the pathogenesis of autoimmune diseases. AIM: To estimate whether the
      CYP2D6 genotype may be considered a predisposing factor in autoimmune bullous
      diseases induction. MATERIAL AND METHODS: The study included 72 patients with
      autoimmune bullous diseases: 37 with pemphigoid, 21 with pemphigus, and 14 with
      dermatitis herpetiformis (DH). The CYP2D6 genotypes were analyzed by the
      polymerase chain reaction fragment length polymorphism (PCR-RFLP) method.
      RESULTS: Relative risk of DH development for particular genotype carriers
      expressed by odds ratio (OR) was statistically significantly higher for subjects
      with CYP2D6*1/CYP2D6*4 (OR = 4.2; p = 0.0104) and 2-fold higher for subjects with
      CYP2D6*4 (OR = 2.3; p = 0.0351). CONCLUSIONS: The results of the present study
      show that the CYP2D6 oxidation polymorphism cannot be considered a risk factor
      for development of pemphigoid and pemphigus, however it might have an impact on
      dermatitis herpetiformis.

PMID- 24278078
TI  - Analysis of the impact of selected socio-demographic factors on quality of life
      of asthma patients.
AB  - AIM: To evaluate the influence of selected socio-demographic factors on quality
      of life of patients with different degrees of asthma severity. MATERIAL AND
      METHODS: The study was conducted in 2009-2010 in the Clinic of Allergology,
      Clinical Immunology and Internal Diseases in Dr J. Biziel University Hospital No.
      2 in Bydgoszcz. Patients were divided into a tested group (126) and a control
      group (86). The criterion for the division was the degree of asthma control
      according to GINA 2006. The following tools were used: the author's questionnaire
      containing questions about socio-demographic and clinical data, and the WHOQOL
      100. RESULTS: In the tested group, a statistically significant correlation was
      observed between quality of life and age (p < 0.002 for the entire population),
      education (p < 0.05 in the group with controlled asthma, p = 0.0005 for the
      entire population), professional activity (p < 0.003 in the group with partially
      controlled asthma, p < 0.05 with uncontrolled asthma and p < 0.0001 in the entire
      population), marital status (p = 0.025 for the entire population) and financial
      situation (p < 0.0001; p < 0.0002; p < 0.009 in all groups; p < 0.0001 in the
      entire population). There was no significant difference between quality of life,
      and sex and the place of residence of the respondents. CONCLUSIONS: Age,
      education, professional activity, marital status and financial situation affect
      the assessment of quality of life in patients with asthma. Socio-demographic
      factors such as sex and the place of residence do not influence the assessment of
      quality of life in patients with asthma.

PMID- 24278079
TI  - Whitening efficacy of plant extracts including Hippophae rhamnoides and Cassia
      fistula extracts on the skin of Asian patients with melasma.
AB  - INTRODUCTION: Melasma/hyperpigmentation and solar damage of the skin remains a
      difficult problem to treat. Various types of whitening agents are used to treat
      hyperpigmentation. A change has been observed recently to use plant extracts as
      skin whitening agents. AIM: To compare the effectiveness of emulsion formulations
      containing plant extracts that include catechins/polyphenols and placebo without
      plant extracts, on patients with melasma. MATERIAL AND METHODS: Two groups of 25
      patients each (aged 21-35 years), who reported to the outpatient department of BV
      Hospital and Personal clinic of a dermatologist, were included in the study.
      Volunteers applied the formulations with plant extracts and placebo to one side
      of the cheek. Prior to the study, signed consent was obtained from each patient.
      The tyrosinase inhibitory activity of the extracts and formulations was tested in
      vitro. The pigment density of patients was evaluated biometrologically using
      Mexameter((r)) and subjectively using a visual survey before and after treatment
      of 12 weeks. The approval of the Institutional Ethics Committee of Faculty of
      Pharmacy, the Islamia University of Bahawalpur was obtained before the study. One
      way ANOVA and Kruskal-Wallis tests were used in the statistical analysis.
      RESULTS: A significant decrease in the level of melanin was determined in all 50
      patients who used a plant extract containing catechin (p <= 0.05). The difference
      between pre- and post-treatment levels of melanin was statistically significant
      (p = 0.05). Formulations prepared with plant extracts containing catechin were
      found effective on melasma, compared to the placebo. CONCLUSIONS: Formulations
      containing plant extracts that are not yet being used widespread commercially on
      melasma could be an effective alternative treatment of melasma.

PMID- 24278080
TI  - Disease-induced level of shame in patients with acne, psoriasis and syphilis.
AB  - INTRODUCTION: A prolonged feeling of shame leads to particularly negative
      consequences and it accompanies, as well as triggers, any kind of stigma. AIM: AS
      EMPIRICAL WORKS ON SHAME DUE TO STIGMATIZING DISEASES ARE SCARCE, THE AUTHORS
      AIMED TO INVESTIGATE THE FOLLOWING: 1) which diseases are perceived as the most
      embarrassing, and 2) what level of shame is attributed to the embarrassing
      diseases by affected patients. Additionally, the authors assumed that the
      differentiation variable for the second aim would be the level of infectiousness
      (or non-infectiousness) of a given disease. MATERIAL AND METHODS: A two-stage
      study was carried out in 2011-2013. Three groups of patients affected by various
      diseases were included into the actual study: 1) people suffering from non
      infectious (42 psoriasis and 42 acne subjects) and 2) infectious (25 syphilis
      cases) diseases. The patients filled in an original questionnaire, designed
      especially for the purpose of the study. RESULTS: As the most shameful acne
      patients consider syphilis, but patients with syphilis - AIDS. Patients with
      syphilis assigned to their disease the greatest shame (average 75%), and the
      lowest - acne patients (average 30%). Patients with psoriasis assessed on 52%
      shame experienced because of the disease. CONCLUSIONS: The conducted study
      confirmed the accuracy of the empirical assumptions which may be applicable in
      prevention as well as therapy of negative consequences of shame.

PMID- 24278081
TI  - The pilot study assessing efficacy and versatility of novel therapy for
      neoplastic ulceration: clinical and microbiological aspects.
AB  - INTRODUCTION: Neoplastic ulcers are chronic and, most often, irreversible lesions
      caused by proliferation of tumor cells infiltrating and damaging skin tissues.
      The treatment of neoplastic ulcers is a very difficult and time-consuming
      process. So, is very important to find methods of controlling this type of
      chronic wounds. AIM: To evaluate the efficiency of monitored treatment of
      neoplastic ulcers by means of providing moist wound environment dressings and
      antiseptic to the group of patients with an advanced stage of tumor, with
      particular focus on the impact of the treatment applied on the clinical condition
      of the ulcers; to evaluate the impact of the treatment applied on the dynamics of
      bacterial flora in neoplastic ulcers, with particular focus on the presence of
      alarm pathogens; to conduct a risk analysis of the occurrence of local and
      systemic complications during treatment. MATERIAL AND METHODS: This was a
      prospective pilot clinical study of 30 patients with malignant ulcers, 13 male
      and 17 female aged from 24 to 92 years treated with octenidine antiseptic and
      dressing set for 3 weeks. The wounds were clinically assessed for the changes of
      amount of necrotic tissue, exudate level and type, malodour and pain level during
      treatment. At the baseline and after 3 weeks of treatment, the wounds were
      swabbed for microbiological assessment. RESULTS: The used scheme of treatment is
      efficient and brings clinical improvement in all treated ulcers. During the 3
      week treatment, reduction of necrotic tissue, decrease in the level of exudate,
      pain and malodour was observed in all patients (p < 0.05). High activity of
      octenidine against Gram(-) and Gram(+) bacteria was observed. The use of
      octenidine dihydrochloride correlated with a progressing eradication of
      multiresistant strains and alarm pathogens (p < 0.001). No serious adverse
      effects or significant symptoms of intolerance of the applied treatment were
      observed.

PMID- 24278082
TI  - Optical radiation in modern medicine.
AB  - Optical radiation extends between microwaves and X-rays of the electromagnetic
      radiation and includes ultraviolet (UV), visible light (VL) and infrared (IR)
      components. The dose of radiation that reaches the skin is influenced by the
      ozone layer, position of the Sun, latitude, altitude, cloud cover and ground
      reflections. The photobiological effects of UV, VL and IR bands depend on their
      wavelength, frequency and mechanism of action. They are modified by the
      thickness, structure, vasculature and pigmentation of skin's stratum corneum,
      epidermis and dermis. Following absorption, IR affects the body mainly through
      transfer of thermal energy to tissues. Visible light and skin interact either
      thermally or photochemically, whereas UV acts mainly photochemically. Optical
      radiation in the form of sunlight therapy had been used already in ancient times.
      Nowadays IR, VL and UV are widely applied in the therapy of allergic,
      dermatological, cardiovascular, respiratory, rheumatic, neonatal, pediatric and
      psychiatric disorders. 

PMID- 24278083
TI  - Dermoscopy on nevus comedonicus: a case report and review of the literature.
AB  - Nevus comedonicus (NC) is a very rare, benign hamartoma characterised by the
      occurrence of dilated, comedo-like openings, typically on the face, neck, upper
      arms, chest or abdomen. In uncertain cases, histopathological examination
      confirms the diagnosis. The authors suggest dermoscopy as a rapid and useful
      method of initial diagnosis of nevus comedonicus based upon its distinctive
      dermoscopic features. The dermoscopy reveals numerous light- and dark-brown,
      circular or barrel-shaped, homogenous areas with prominent keratin plugs. 

PMID- 24278084
TI  - Acne inversa goes an extra mile than hidradenitis suppurativa.
AB  - Acne inversa (AI, hidradenitis suppurativa, Velpeau's disease, Verneuil's
      disease) is a severe, chronic inflammatory dermatosis of unknown etiology,
      detected on the basis of clinical symptoms more frequently in women than in men.
      Purulent lesions in the form of nodules and inflammatory tumors, fistulas and
      scars are present in the areas with hair follicles and apocrine glands, most
      commonly on the armpits, groin, around the anus and pubic region. Acne inversa
      can lead to physical and mental disorders. Unfortunately, it is often
      misdiagnosed and ineffectively treated. The paper presents a case of a 46-year
      old patient who was successfully treated surgically for AI around the anus and
      buttocks by excision of the changes and closure of the wound with local flaps and
      split-thickness skin grafts, taken with dermatome from the rear surface of the
      thighs. Surgical treatment is the method of choice in the treatment of severe AI.

PMID- 24278085
TI  - Terbinafine-induced subacute cutaneous lupus erythematosus in two patients with
      systemic lupus erythematosus successfully treated with topical corticosteroids.
AB  - So far in the literature there have been reported only 5 patients with a
      recognized and well-documented history of systemic lupus erythematosus (SLE) who
      developed SCLE after terbinafine introduction. Here we report two women suffering
      from SLE who developed SCLE after initiation of oral terbinafine for
      onychomycosis. Skin lesions in both of them were extensive, located on the trunk,
      and upper and lower extremities. No exacerbation of SLE symptoms was observed at
      that time. Despite severe skin lesions, patients revealed good response to
      topical corticosteroids within a few weeks. The systemic review of the literature
      and our experience on terbinafine-induced SCLE developing in patients with SLE
      allowed to create a description for this special subset: a) terbinafine-induced
      SCLE usually develop in 1-8 weeks after terbinafine introduction, b) skin lesions
      are usually severe, disseminated including lower extremities, c) patients present
      Ro/SS-A La/SS-B antibodies, but anti-histone antibodies are rarely observed, d)
      exacerbation of SLE symptoms is rather not observed, e) eruptions clear within 2
      8 weeks, f) withdrawal of terbinafine and topical corticosteroids should be
      considered as a first-line therapy in these cases, g) terbinafine should be
      carefully used in patients suffering from SLE. 

PMID- 24278086
TI  - Generalized lichen amyloidosis and hyperthyroidism: coincidence or association.
AB  - A 76-year-old white man presented with severe pruritic eruption on both of the
      extremities and lumbar area for 2 years. The dermatological examination showed
      multiple, 1-2 mm sized, hyperpigmented and hyperkeratotic papules which coalesced
      to form poorly delineated plaques spread on the lumbosacral area, lateral and
      extensor surfaces of thighs, arms and forearms. The histopathological examination
      revealed eosinophilic amorphous material in papillary dermis that was stained
      positively with crystal violet stain. The patient was diagnosed as generalized
      lichen amyloidosis (LA) clinically and histopathologically. Routine laboratory
      tests were within normal limits except thyroid function tests. The thyroid
      stimulating hormone level was decreased, while the thyroxine level was increased.
      Ultrasonography showed enlarged and heterogeneous thyroid gland. Thyroid
      autoantibodies were within normal limits. An association between LA and other
      diseases such as atopic dermatitis, lichen planus, mycosis fungoides, chronic
      urticaria, HIV infection, multiple endocrine neoplasia type 2A, and angiolymphoid
      hyperplasia with eosinophilia have been defined. However, there is no reported LA
      case associated with hyperthyroidism in the literature. We think that the same
      etiologic factor might have triggered both diseases, or hyperthyroidism, by
      causing the itching, might have induced the occurrence or spread of LA. 

PMID- 24278087
TI  - A case of diffuse large B-cell lymphoma misdiagnosed as an erysipelas of the
      face.
AB  - We report a case of a woman with diffuse large B-cell lymphoma (DLBCL). Primary
      cutaneous lymphomas (PCLs) represent distinct clinical and histopathologic
      subtypes of extranodal T- and B-cell lymphomas. Cutaneous B-cell lymphomas
      comprise 20-25% of all primary cutaneous lymphomas. The patient presented an
      erythematous tumour mass of the left nasolabial fold, nose and left cheek as well
      as disseminated infiltrative plagues on the trunk, arms and left lower leg. Skin
      biopsy revealed a diffuse infiltrate of lymphocytes around hair follicles and
      blood vessels within dermis and subcutaneous tissue. An immunohistochemistry
      showed a diffuse infiltrate of large non-cleaved B-cells, with a high proportion
      of centroblast-like cells within dermis. Tumor cells expressed CD20, bcl-2
      protein and did not express CD10. The patient was misdiagnosed as the erysipelas
      of the face and unsuccessfully treated with long-term antibiotic therapy by a
      laryngologist and a dermatologist. The correct diagnosis was delayed and
      established after 6 months' history of DLBCL lesions. Therefore, we would like to
      strongly stress the importance of considering diagnosis of cutaneous lymphomas in
      chronic skin lesions non-responsive to adequate therapies. 

PMID- 24278089
TI  - Polymorphic Amplified Typing Sequences (PATS) Strain Typing System Accurately
      Discriminates a Set of Temporally and Spatially Disparate Escherichia coli O157
      Isolates Associated with Human Infection.
AB  - Polymorphic Amplified Typing Sequences (PATS) is a PCR-based Escherichia coli
      O157 (O157) strain typing system. Here, we show that PATS compares excellently
      with Pulsed-Field Gel Electrophoresis (PFGE) in that both methods cluster
      geographically diverse O157 isolates similarly. Comparative analysis of the
      results obtained in this simulated "blind" study attests to the discriminating
      power and applicability of PATS to epidemiological/nosocomial situations. 

PMID- 24278088
TI  - Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Social Anxiety
      Disorder: Case Reports and a Review of the Literature.
AB  - OBJECTIVES: Social anxiety disorder (SAD) is a common and debilitating anxiety
      disorders. However, few studies had been dedicated to the neurobiology underlying
      SAD until the last decade. Rates of non-responders to standard methods of
      treatment remain unsatisfactorily high of approximately 25%, including SAD.
      Advances in our understanding of SAD could lead to new treatment strategies. A
      potential non invasive therapeutic option is repetitive transcranial magnetic
      stimulation (rTMS). Thus, we reported two cases of SAD treated with rTMS Methods:
      The bibliographical search used Pubmed/Medline, ISI Web of Knowledge and Scielo
      databases. The terms chosen for the search were: anxiety disorders, neuroimaging,
      repetitive transcranial magnetic stimulation. RESULTS: In most of the studies
      conducted on anxiety disorders, except SAD, the right prefrontal cortex (PFC),
      more specifically dorsolateral PFC was stimulated, with marked results when
      applying high-rTMS compared with studies stimulating the opposite side. However,
      according to the "valence hypothesis", anxiety disorders might be characterized
      by an interhemispheric imbalance associated with increased right-hemispheric
      activity. With regard to the two cases treated with rTMS, we found a decrease in
      BDI, BAI and LSAS scores from baseline to follow-up. CONCLUSION: We hypothesize
      that the application of low-rTMS over the right medial PFC (mPFC; the main
      structure involved in SAD circuitry) combined with high-rTMS over the left mPFC,
      for at least 4 weeks on consecutive weekdays, may induce a balance in brain
      activity, opening an attractive therapeutic option for the treatment of SAD.

PMID- 24278090
TI  - Cross-linking as an adjuvant treatment for tectonic corneal lamellar graft
      preparation.
AB  - PURPOSE: To describe a new surgical approach for the tectonic reconstruction of
      the anterior ocular segment and the management of scleral and conjuctival
      melting. METHODS: Case series of patients demonstrating anterior segment
      anomalies, such as scleral and conjunctival melting. The anterior stromal part of
      a pre-cut corneal graft for Descemet's stripping automated endothelial
      keratoplasty (DSAEK) was cross-linked with riboflavin and ultraviolet A
      irradiation and was used to cover scleral (scleral melting in a patient with
      necrotizing scleritis, one case) and conjuctival (dehiscence of the conjunctiva
      in patients with anti-glaucomatous valve exposure, two cases) areas. The
      endothelial part of all corneal grafts was used for DSAEK in patients with need
      of corneal endothelial transplantation. RESULTS: Repair of scleral and
      conjuctival melting was successful in all cases. No intra- or post- operative
      complications occured. Visual acuity of all patients remained stable during the
      follow up period. One year postoperatively the corneal graft remained in place
      and no signs of inflammation were evident, while all grafts were epithelialized.
      CONCLUSIONS: The use of cross-linked corneal graft for the tectonic
      reconstruction of the anterior ocular segment represents an adequate surgical
      approach for the management of scleral and conjuctival melting; while, at the
      same time it offers the advantage of using one corneal graft for two recipients.

PMID- 24278091
TI  - Abstracts from the canadian consensus conference on dementia.

PMID- 24278092
TI  - The Value of Admission Clinical Data for Diagnosing Heart Failure in Long-term
      Care.
AB  - BACKGROUND: Heart failure (HF) is common in long-term care (LTC). Diagnostic
      uncertainty is important barrier to optimal HF management, stemming from
      inadequate health information transfer upon LTC admission. We determine the
      utility of admission clinical information to confirm a HF diagnosis in new LTC
      residents. METHODS: This was a prospective cohort study. From February 2004 to
      November 2006, information about new residents from 41 LTC homes in Ontario,
      Canada, was collected from residents and caregivers, and all available health
      records. A prior HF diagnosis was confirmed by consensus review of available data
      by two independent experts. Multivariate modelling was utilized to determine the
      utility of the admission clinical assessment in confirming a prior HF diagnosis.
      RESULTS: A total of 449 residents were included for analysis, aged 84.3+/-6.5
      years, and 21.6% had a prior HF diagnosis. The most useful clinical item for
      diagnosing HF was a "history of HF". The final model included "history of HF' (OR
      [odds ratio] 13.66, 95% CI 6.61-28.24), "fluid on the lungs" (OR 2.01, 95% CI
      1.04-3.89), "orthopnea" (OR 1.76, 95% CI 0.93-3.33), "taking beta-blocker" (OR
      2.09, 95% CI 1.10-3.94), "taking loop diuretics" (OR 2.11, 95% CI 1.12-3.98), and
      "history of coronary artery disease" (OR 2.83, 95% CI 1.42-5.64). CONCLUSION:
      Elements of the clinical assessment for new LTC residents can help confirm a
      prior HF diagnosis. An admission history of HF is highly predictive.

PMID- 24278093
TI  - The Role of Support Services in Promoting Social Inclusion for the Disadvantaged
      Urban-dwelling Elderly.
AB  - BACKGROUND: Disadvantaged older adults living in non-family situations in Toronto
      are more likely than older adults living in family situations to have less
      economic security, less social support, and less choice in housing. Older adults
      who live in poverty and are precariously housed are more likely to be chronically
      ill, to live with multiple illnesses, to have poor nutrition, high stress and
      loneliness, all of which are strongly associated with the determinant of health
      social exclusion. The aim of this study is to: 1) evaluate the level of social
      disadvantage and exclusion experienced by low-income older adults 65 years of age
      and older living alone or in non-family situations; 2) assess the level of
      dependency on government and community services (support services) to maintain a
      reasonable standard of living (minimize effects of social exclusion); and 3)
      identify consequences of social exclusion not addressed by current available
      services. METHODS: Fifteen male older adult members of the Good Neighbours' Club
      in downtown Toronto were interviewed. Semi-structured questionnaires assessed
      barriers to, utility of, and perceived impact of support services available to
      disadvantaged older adults living in the central core of southeast Toronto.
      RESULTS: Support services for income, housing, food security, social support, and
      health care do mitigate the effects of social exclusion in the study
      participants. Data gathered from interviews identified factors that counter the
      efforts by support services to increase social inclusion in this population.
      CONCLUSIONS: Support services reduce social isolation experienced by these older
      adults. Evidence of the detrimental impact of low financial literacy suggests a
      need to design and implement training programs to build the older adults'
      capacity to manage their own finances effectively, and resist falling victim to
      financial fraud.

PMID- 24278094
TI  - Responsiveness of the QUALID to Improved Neuropsychiatric Symptoms in Patients
      with Alzheimer's Disease.
AB  - BACKGROUND: This study aimed to determine whether the Quality of Life in Late
      Stage Dementia (QUALID) scale is responsive to changes in behaviour due to
      therapeutic intervention. METHOD: 31 long-term care residents with moderate to
      severe AD and agitation/aggression entered a three-month, open-label trial of
      memantine 10 mg BID. The relationships between the QUALID and BPSD, global
      improvement, and cognition at baseline and endpoint, as well as the changes in
      these scales as a result of treatment, were examined. RESULTS: Despite a
      significant improvement in agitation and aggression (NPI agitation, F3,90 =
      3.721, p =.014; CMAI total, F3,90 = 6.301, p =.001) and overall behaviour (NPI
      total, F3,90 = 4.035, p =.010), there was no significant change in QUALID score
      (t30 = -0.278, p =.783). The QUALID was correlated with NPI at baseline (tau =
      0.270, p =.037) and endpoint (tau = 0.404, p =.002), but change scores were not
      correlated (tau = 0.107, p =.412). CONCLUSION: While the QUALID correlates with
      behavioural measures at single time points, it does not appear to correlate with
      changes longitudinally associated with treatment.

PMID- 24278095
TI  - Hypovitaminosis D in Delirium: a Retrospective Cross-sectional Study.
AB  - BACKGROUND: As vitamin D may have a neuroprotective effect, the authors studied
      the association of biomarkers of vitamin D status and delirium to see if low
      vitamin D status was common in delirium cases. METHODS: Biochemical measures of
      vitamin D (25-hydroxyvitamin D [25-OHD]) and calcium metabolism were used in this
      retrospective cross-sectional analysis of adult in-patients with delirium,
      admitted at three Canadian academic hospitals from January 2011 to July 2012.
      Primary outcome was to determine estimates of the prevalence of hypovitaminosis D
      in this group in whom vitamin D was checked. RESULTS: Seventy-one (5.8%) out of
      1,232 delirium inpatients had their vitamin D measured. Thirty-nine (55%) showed
      vitamin D insufficiency (25-OHD of 25-75 nmol/L) and 8 (11%) showed vitamin D
      deficiency (25-OHD < 25 nmol/L). Mean serum 25-OHD levels were lower in males
      (57.1+/-7.7 nmol/L) than in females (78.2+/-6.1 nmol/L), p = .01, even when
      controlled for age and season. Men were younger than the women (74.4+/-2.3 vs.
      82.4+/-1.7, p = .005). Mean age was 78.7+/-1.5 years, and 33 (47%) were male.
      CONCLUSIONS: Although vitamin D is rarely checked during delirium workup and/or
      management, high rates of hypovitaminosis D were found to be common in the
      delirium in-patients in whom it was checked. Larger studies would be needed to
      estimate the prevalence of hypovitaminosis D in delirium and whether
      hypovitaminosis D plays a role in the pathogenesis of delirium.

PMID- 24278096
TI  - Geriatric medicine leadership of health care transformation: to be or not to be?
AB  - Geriatric Medicine is well-suited to inform and lead health-care system redesign
      to address the needs of seniors with complex conditions. We posit that
      geriatricians must urgently consider how to "brand" Geriatric Medicine in a
      manner that garners active support from those outside the specialty, including
      how to adapt practice patterns to better meet the needs of patients and of the
      health-care system. 

PMID- 24278097
TI  - Polyester MU-assay chip for stem cell studies.
AB  - The application of microfluidic technologies to stem cell research is of great
      interest to biologists and bioengineers. This is chiefly due to the intricate
      ability to control the cellular environment, the reduction of reagent volume,
      experimentation time and cost, and the high-throughput screening capabilities of
      microscale devices. Despite this importance, a simple-to-use microfluidic
      platform for studying the effects of growth factors on stem cell differentiation
      has not yet emerged. With this consideration, we have designed and characterized
      a microfluidic device that is easy to fabricate and operate, yet contains several
      functional elements. Our device is a simple polyester-based microfluidic chip
      capable of simultaneously screening multiple independent stem cell culture
      conditions. Generated by laser ablation and stacking of multiple layers of
      polyester film, this device integrates a 10 * 10 microwell array for cell culture
      with a continuous perfusion system and a non-linear concentration gradient
      generator. We performed numerical calculations to predict the gradient formation
      and calculate the shear stress acting on the cells inside the device. The device
      operation was validated by culturing murine embryonic stem cells inside the
      microwells for 5 days. Furthermore, we showed the ability to maintain the
      pluripotency of stem cell aggregates in response to concentrations of leukemia
      inhibitory factor ranging from 0 to ~1000 U/ml. Given its simplicity, fast
      manufacturing method, scalability, and the cell-compatible nature of the device,
      it may be a useful platform for long-term stem cell culture and studies. 

PMID- 24278098
TI  - Influence of buoyancy-driven flow on mass transfer in a two-stream microfluidic
      channel: Introduction of cryoprotective agents into cell suspensions.
AB  - A variety of methods have been used to introduce chemicals into a stream or to
      mix two or more streams of different compositions using microfluidic devices. In
      the following paper, the introduction of cryoprotective agents (CPAs) used during
      cryopreservation of cells in order to protect them from freezing injuries and
      increase viability post thaw is described. Dimethylsulphoxide (DMSO) is the most
      commonly used CPA. We aim to optimize the operating conditions of a two-stream
      microfluidic device to introduce a 10% vol/vol solution of DMSO into a cell
      suspension. Transport behavior of DMSO between two streams in the device has been
      experimentally characterized for a spectrum of flow conditions (0.7 < Re < 10),
      varying initial donor stream concentrations, (1% vol/vol < C o  < 15% vol/vol)
      and different flow rate fractions (0.23 < f q  < 0.77). The outlet cell stream
      concentration is analyzed for two different flow configurations: one with the
      cell stream flowing on top of the DMSO-rich donor stream, and the other with the
      cell stream flowing beneath the heavy DMSO-laden stream. We establish a
      transition from a diffusive mode of mass transfer to gravity-influenced
      convective currents for Atwood numbers (A t ) in the range of (1.7 * 10(-3) < A t
      < 3.1 * 10(-3)) for the latter configuration. Flow visualization with cells
      further our understanding of the effect of A t on the nature of mass transport.
      Cell motion studies performed with Jurkat cells confirm a high cell recovery from
      the device while underscoring the need to collect both the streams at the outlet
      of the device and suggesting flow conditions that will help us achieve the target
      DMSO outlet concentration for clinical scale flow rates of the cell suspension. 

PMID- 24278099
TI  - Ox-LDL induces ER stress and promotes the adipokines secretion in 3T3-L1
      adipocytes.
AB  - Adipocytes behave as a rich source of adipokines, which may be the link between
      obesity and its complications. Endoplasmic reticulum (ER) stress in adipocytes
      can modulate adipokines secretion. The aim of this study is to evaluate the
      effect of oxidized low density lipoprotein (ox-LDL) treatment on ER stress and
      adipokines secretion in differentiated adipocytes. 3T3-L1 pre-adipocytes were
      cultured and differentiated into mature adipocytes in vitro. Differentiated
      adipocytes were incubated with various concentrations of ox-LDL (0-100 ug/ml) for
      48 hours; 50 ug/ml ox-LDL for various times (0-48 hours) with or without
      tauroursodeoxycholic acid (TUDCA) (0-400 uM) pre-treatment. The protein
      expressions of ER stress markers, glucose regulated protein 78(GRP78) and
      CCAAT/enhancer binding protein [C/EBP] homologous protein (CHOP) in adipocytes
      were detected by Western blot. The mRNA expressions of visfatin and resistin were
      measured by real-time PCR and the protein release of visfatin and resistin in
      supernatant were determined by ELISA. Treatment with ox-LDL could increase the
      cholesterol concentration in adipocytes. Ox-LDL induced the expressions of GRP78
      and CHOP protein in adipocytes and promoted visfatin and resistin secretion in
      culture medium in dose and time-dependent manner. TUDCA could attenuate the
      effect of ox-LDL on GRP78 and CHOP expressions and reduce visfatin and resistin
      at mRNA and protein level in dose-dependent manner. In conclusion, ox-LDL
      promoted the expression and secretion of visfatin and resistin through its
      activation of ER stress, which may be related to the increase of cholesterol load
      in adipocytes.

PMID- 24278101
TI  - Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and
      senescence in a Sirt1-dependent manner.
AB  - Resveratrol, a naturally occurring polyphenolic compound, has been reported to
      exert anticancer activity by affecting diverse molecular targets. In this study,
      we examined the effects and the underlying mechanisms of resveratrol on gastric
      cancer. We found that resveratrol inhibited the proliferation of gastric cancer
      cells in a dose-dependent manner. At the concentration of 25 and 50 uM,
      resveratrol inhibited the cell viability and diminished the clonogenic potential
      of gastric cancer cells. Resveratrol treatment arrested gastric cancer cells in
      the G1 phase and led to senescence instead of apoptosis. Regulators of the cell
      cycle and senescence pathways, including cyclin D1, cyclin-dependent kinase (CDK4
      and 6), p21 and p16, were dysregulated by resveratrol treatment. The inhibitory
      effects of resveratrol on gastric cancer were also verified in vivo using a nude
      mice xenograft model. Resveratrol (40 mg/kg/d) exerted inhibitory activities on
      gastric cancer development and significantly decreased the fractions of Ki67
      positive cells in the tumor specimens from the nude mice. After resveratrol
      treatment, the induction of senescence and the changes in the expression of the
      regulators involved in the cell cycle and senescence pathways were similar to
      what we observed in vitro. However, the depletion of Sirtuin (Sirt)1 reversed the
      above-described effects of resveratrol both in vitro and in vivo. Our data
      suggest that resveratrol inhibits gastric cancer in a Sirt1-dependent manner and
      provide detailed evidence for the possibility of applying resveratrol in gastric
      cancer prevention and therapy. 

PMID- 24278102
TI  - The microRNAome of pregnancy: deciphering miRNA networks at the maternal-fetal
      interface.
AB  - MicroRNAs (miRNAs) post-transcriptionally regulate a vast network of genes by
      inhibiting mRNA translation. Aberrant miRNA expression profiles have been
      implicated in pathologies and physiological processes including pregnancy and
      angiogenesis. Using our established model of implantation failure and spontaneous
      fetal loss in pigs (Sus scrofa), 236 miRNAs were profiled and compared between 1)
      non-pregnant and pregnant endometrium, 2) maternal and fetal tissues, and 3)
      viable and growth-arrested conceptus attachment sites by microarray and Real-Time
      PCR. Many significant differences in miRNA expression were observed between each
      of the aforementioned comparisons, and several were validated by PCR. Results
      indicated which miRNAs were important during pregnancy, which were elevated on
      the maternal or fetal side of the maternal-fetal interface, and they implicated
      the maternal expression of miR-10a, 27a, 29c, 323, 331-5p, 339-3p, 374b-5p, and
      935 in the spontaneous loss observed in pigs. Several putative mRNA targets of
      the miRNAs (elevated in endometrium associated with arresting conceptuses) were
      assessed by quantitative Real-Time PCR and were depressed, supporting their
      regulation by miRNAs. Finally, targets were clustered by function to obtain
      ranked lists of gene networks that indicated which pathways/physiological
      processes might be important in non-pregnant (extracellular matrix factors)
      versus pregnant endometrium (nuclear transcription factor regulation), maternal
      (blood vessel development) versus fetal (neuronal differentiation) tissue, and
      healthy (extracellular matrix factors) versus arresting (GRAM domain) conceptus
      attachment sites. Overall, we demonstrate the presence of miRNAs on both sides of
      the maternal-fetal interface, implicate them in spontaneous fetal loss, and
      present a unique glimpse into the vast microRNAome of pregnancy. 

PMID- 24278103
TI  - Low frequency magnetic fields enhance antitumor immune response against mouse H22
      hepatocellular carcinoma.
AB  - OBJECTIVE: Many studies have shown that magnetic fields (MF) inhibit tumor growth
      and influence the function of immune system. However, the effect of MF on
      mechanism of immunological function in tumor-bearing mice is still unclear.
      METHODS: In this study, tumor-bearing mice were prepared by subcutaneously
      inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then
      exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor
      growth and the innate and adaptive immune parameters were measured. RESULTS: MF
      treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth
      (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced
      production of cytokines including interleukin-6 (IL-6), granulocyte colony-
      stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9-10,
      p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of
      macrophages and dendritic cells, enhanced profiles of CD4(+) T and CD8(+) T
      lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg
      cells (n = 9-10, p<0.05 or 0.01) in the mice model. CONCLUSION: The inhibitory
      effect of MF on tumor growth was related to the improvement of immune function in
      the tumor-bearing mice.

PMID- 24278104
TI  - Identification of an intrinsic determinant critical for maspin subcellular
      localization and function.
AB  - Maspin, a multifaceted tumor suppressor, belongs to the serine protease inhibitor
      superfamily, but only inhibits serine protease-like enzymes such as histone
      deacetylase 1 (HDAC1). Maspin is specifically expressed in epithelial cells and
      it is differentially regulated during tumor progression. A new emerging consensus
      suggests that a shift in maspin subcellular localization from the nucleus to the
      cytoplasm stratifies with poor cancer prognosis. In the current study, we
      employed a rational mutagenesis approach and showed that maspin reactive center
      loop (RCL) and its neighboring sequence are critical for maspin stability.
      Further, when expressed in multiple tumor cell lines, single point mutation of
      Aspartate(346) (D(346)) to Glutamate (E(346)), maspin(D346E), was predominantly
      nuclear, whereas wild type maspin (maspin(WT)) was both cytoplasmic and nuclear.
      Evidence from cellular fractionation followed by immunological and proteomic
      protein identification, combined with the evidence from fluorescent imaging of
      endogenous proteins, fluorescent protein fusion constructs, as well as
      bimolecular fluorescence complementation (BiFC) showed that the increased nuclear
      enrichment of maspin(D346E) was, at least in part, due to its increased affinity
      to HDAC1. Maspin(D346E) was also more potent than maspin(WT) as an HDAC
      inhibitor. Taken together, our evidence demonstrates that D(346) is a critical
      cis-element in maspin sequence that determines the molecular context and
      subcellular localization of maspin. A mechanistic model derived from our evidence
      suggests a new window of opportunity for the development of maspin-based
      biologically competent HDAC inhibitors for cancer treatment. 

PMID- 24278105
TI  - Early evidence of Acheulean settlement in northwestern Europe--la Noira site, a
      700,000 year-old occupation in the center of France.
AB  - The human settlement of Europe during Pleistocene times was sporadic and several
      stages have been recognized, both from paleaoanthropological and archaeological
      records. If the first phase of hominin occupation (as early as 1.4 Ma) seems
      mainly restricted to the southern part of the continent, the second phase,
      characterized by specific lithic tools (handaxes), is linked to Acheulean
      settlements and to the emergence of Homo heidelbergensis, the ancestor of
      Neanderthals. This phase reached northwestern Europe and is documented in
      numerous sites in Germany, Great Britain and northern France, generally after 600
      ka. At la Noira (Brinay, Central France), the Middle Pleistocene alluvial
      formation of the Cher River covers an archaeological level associated with a
      slope deposit (diamicton). The lithic assemblage from this level includes Large
      Cutting Tools (LCTs), flakes and cores, associated with numerous millstone slabs.
      The lithic series is classified as Acheulean on the basis of both technological
      and typological analyses. Cryoturbation features indicate that the slope deposits
      and associated archaeological level were strongly frozen and disturbed after
      hominin occupation and before fluvial deposition. Eight sediment samples were
      dated by the electron spin resonance (ESR) method and the weighted average age
      obtained for the fluvial sands overlying the slope deposits is 665+/-55 ka. This
      age is older than previous chronological data placing the first European
      Acheulean assemblages north of 45(th) parallel north at around 500 ka and
      modifies our current vision of the initial peopling of northern Europe. Acheulean
      settlements are older than previously assumed and the oldest evidences are not
      only located in southern Europe. La Noira is the oldest evidence of Acheulean
      presence in north-western Europe and attests to the possibility of pioneering
      phases of Acheulean settlement which would have taken place on a Mode 1-type
      substratum as early as 700 ka. The lithic assemblage from la Noira thus provides
      behavioral and technological data on early Acheulean occupation in Europe and
      contributes to our understanding of the diffusion of this tradition. 

PMID- 24278106
TI  - Hypoxia limits inhibitory effects of Zn2+ on spreading depolarizations.
AB  - Spreading depolarizations (SDs) are coordinated depolarizations of brain tissue
      that have been well-characterized in animal models and more recently implicated
      in the progression of stroke injury. We previously showed that extracellular
      Zn(2+) accumulation can inhibit the propagation of SD events. In that prior work,
      Zn(2+) was tested in normoxic conditions, where SD was generated by localized KCl
      pulses in oxygenated tissue. The current study examined the extent to which
      Zn(2+) effects are modified by hypoxia, to assess potential implications for
      stroke studies. The present studies examined SD generated in brain slices acutely
      prepared from mice, and recordings were made from the hippocampal CA1 region. SDs
      were generated by either local potassium injection (K-SD), exposure to the
      Na(+)/K(+)-ATPase inhibitor ouabain (ouabain-SD) or superfusion with modified
      ACSF with reduced oxygen and glucose concentrations (oxygen glucose deprivation:
      OGD-SD). Extracellular Zn(2+) exposures (100 uM ZnCl2) effectively decreased SD
      propagation rates and significantly increased the initiation threshold for K-SD
      generated in oxygenated ACSF (95% O2). In contrast, ZnCl2 did not inhibit
      propagation of OGD-SD or ouabain-SD generated in hypoxic conditions. Zn(2+)
      sensitivity in 0% O2 was restored by exposure to the protein oxidizer DTNB,
      suggesting that redox modulation may contribute to resistance to Zn(2+) in
      hypoxic conditions. DTNB pretreatment also significantly potentiated the
      inhibitory effects of competitive (D-AP5) or allosteric (Ro25-6981) NMDA receptor
      antagonists on OGD-SD. Finally, Zn(2+) inhibition of isolated NMDAR currents was
      potentiated by DTNB. Together, these results suggest that hypoxia-induced redox
      modulation can influence the sensitivity of SD to Zn(2+) as well as to other
      NMDAR antagonists. Such a mechanism may limit inhibitory effects of endogenous
      Zn(2+) accumulation in hypoxic regions close to ischemic infarcts. 

PMID- 24278108
TI  - A neuro-mechanical model explaining the physiological role of fast and slow
      muscle fibres at stop and start of stepping of an insect leg.
AB  - Stop and start of stepping are two basic actions of the musculo-skeletal system
      of a leg. Although they are basic phenomena, they require the coordinated
      activities of the leg muscles. However, little is known of the details of how
      these activities are generated by the interactions between the local neuronal
      networks controlling the fast and slow muscle fibres at the individual leg
      joints. In the present work, we aim at uncovering some of those details using a
      suitable neuro-mechanical model. It is an extension of the model in the
      accompanying paper and now includes all three antagonistic muscle pairs of the
      main joints of an insect leg, together with their dedicated neuronal control, as
      well as common inhibitory motoneurons and the residual stiffness of the slow
      muscles. This model enabled us to study putative processes of intra-leg
      coordination during stop and start of stepping. We also made use of the effects
      of sensory signals encoding the position and velocity of the leg joints. Where
      experimental observations are available, the corresponding simulation results are
      in good agreement with them. Our model makes detailed predictions as to the
      coordination processes of the individual muscle systems both at stop and start of
      stepping. In particular, it reveals a possible role of the slow muscle fibres at
      stop in accelerating the convergence of the leg to its steady-state position.
      These findings lend our model physiological relevance and can therefore be used
      to elucidate details of the stop and start of stepping in insects, and perhaps in
      other animals, too. 

PMID- 24278107
TI  - Adolescent health-risk behavior and community disorder.
AB  - BACKGROUND: Various forms of community disorder are associated with health
      outcomes but little is known about how dynamic context where an adolescent spends
      time relates to her health-related behaviors. OBJECTIVE: Assess whether exposure
      to contexts associated with crime (as a marker of community disorder) correlates
      with self-reported health-related behaviors among adolescent girls. METHODS:
      Girls (N = 52), aged 14-17, were recruited from a single geographic urban area
      and monitored for 1 week using a GPS-enabled cell phone. Adolescents completed an
      audio computer-assisted self-administered interview survey on substance use
      (cigarette, alcohol, or marijuana use) and sexual intercourse in the last 30
      days. In addition to recorded home and school address, phones transmitted
      location data every 5 minutes (path points). Using ArcGIS, we defined community
      disorder as aggregated point-level Unified Crime Report data within a 200-meter
      Euclidian buffer from home, school and each path point. Using Stata, we analyzed
      how exposures to areas of higher crime prevalence differed among girls who
      reported each behavior or not. RESULTS: Participants lived and spent time in
      areas with variable crime prevalence within 200 meters of their home, school and
      path points. Significant differences in exposure occurred based on home location
      among girls who reported any substance use or not (p 0.04) and sexual intercourse
      or not (p 0.01). Differences in exposure by school and path points were only
      significant among girls reporting any substance use or not (p 0.03 and 0.02,
      respectively). Exposure also varied by school/non-school day as well as time of
      day. CONCLUSIONS: Adolescent travel patterns are not random. Furthermore, the
      crime context where an adolescent spends time relates to her health-related
      behavior. These data may guide policy relating to crime control and inform time-
      and space-specific interventions to improve adolescent health.

PMID- 24278109
TI  - Effect of two models of intrauterine growth restriction on alveolarization in rat
      lungs: morphometric and gene expression analysis.
AB  - Intrauterine growth restriction (IUGR) in preterm infants increases the risk of
      bronchopulmonary dysplasia, characterized by arrested alveolarization. We
      evaluated the impact of two different rat models (nitric oxide synthase
      inhibition or protein deprivation) of IUGR on alveolarization, before, during,
      and at the end of this postnatal process. We studied IUGR rat pups of dams fed
      either a low protein (LPD) or a normal diet throughout gestation and pups of dams
      treated by continuous infusion of Nomega-nitro-L-arginine methyl ester (L-NAME)
      or its diluent on the last four days of gestation. Morphometric parameters,
      alveolar surface (Svap), mean linear intercept (MLI) and radial alveolar count
      (RAC) and transcriptomic analysis were determined with special focus on genes
      involved in alveolarization. IUGR pups regained normal weight at day 21 in the
      two treated groups. In the LPD group, Svap, MLI and RAC were not different from
      those of controls at day 4, but were significantly decreased at day 21,
      indicating alveolarization arrest. In the L-NAME group, Svap and RAC were
      significantly decreased and MLI was increased at day 4 with complete correction
      at day 21. In the L-NAME model, several factors involved in alveolarization,
      VEGF, VEGF-R1 and -R2, MMP14, MMP16, FGFR3 and 4, FGF18 and 7, were significantly
      decreased at day 4 and/or day 10, while the various factors studied were not
      modified in the LPD group. These results demonstrate that only maternal protein
      deprivation leads to sustained impairment of alveolarization in rat pups, whereas
      L-NAME impairs lung development before alveolarization. Known growth factors
      involved in lung development do not seem to be involved in LPD-induced
      alveolarization disorders, raising the question of a possible programming of
      altered alveolarization. 

PMID- 24278110
TI  - Natural convection flow near a vertical plate that applies a shear stress to a
      viscous fluid.
AB  - The unsteady natural convection flow of an incompressible viscous fluid near a
      vertical plate that applies an arbitrary shear stress to the fluid is studied
      using the Laplace transform technique. The fluid flow is due to both the shear
      and the heating of the plate. Closed-form expressions for velocity and
      temperature are established under the usual Boussinesq approximation. For
      illustration purposes, two special cases are considered and the influence of
      pertinent parameters on the fluid motion is graphically underlined. The required
      time to reach the steady state in the case of oscillating shear stresses on the
      boundary is also determined. 

PMID- 24278111
TI  - The impact of water table drawdown and drying on subterranean aquatic fauna in in
      vitro experiments.
AB  - The abstraction of groundwater is a global phenomenon that directly threatens
      groundwater ecosystems. Despite the global significance of this issue, the impact
      of groundwater abstraction and the lowering of groundwater tables on biota is
      poorly known. The aim of this study is to determine the impacts of groundwater
      drawdown in unconfined aquifers on the distribution of fauna close to the water
      table, and the tolerance of groundwater fauna to sediment drying once water
      levels have declined. A series of column experiments were conducted to
      investigate the depth distribution of different stygofauna (Syncarida and
      Copepoda) under saturated conditions and after fast and slow water table
      declines. Further, the survival of stygofauna under conditions of reduced
      sediment water content was tested. The distribution and response of stygofauna to
      water drawdown was taxon specific, but with the common response of some fauna
      being stranded by water level decline. So too, the survival of stygofauna under
      different levels of sediment saturation was variable. Syncarida were better able
      to tolerate drying conditions than the Copepoda, but mortality of all groups
      increased with decreasing sediment water content. The results of this work
      provide new understanding of the response of fauna to water table drawdown. Such
      improved understanding is necessary for sustainable use of groundwater, and
      allows for targeted strategies to better manage groundwater abstraction and
      maintain groundwater biodiversity. 

PMID- 24278112
TI  - Keep your opponents close: social context affects EEG and fEMG linkage in a turn
      based computer game.
AB  - In daily life, we often copy the gestures and expressions of those we communicate
      with, but recent evidence shows that such mimicry has a physiological
      counterpart: interaction elicits linkage, which is a concordance between the
      biological signals of those involved. To find out how the type of social
      interaction affects linkage, pairs of participants played a turn-based computer
      game in which the level of competition was systematically varied between
      cooperation and competition. Linkage in the beta and gamma frequency bands was
      observed in the EEG, especially when the participants played directly against
      each other. Emotional expression, measured using facial EMG, reflected this
      pattern, with the most competitive condition showing enhanced linkage over the
      facial muscle-regions involved in smiling. These effects were found to be related
      to self-reported social presence: linkage in positive emotional expression was
      associated with self-reported shared negative feelings. The observed effects
      confirmed the hypothesis that the social context affected the degree to which
      participants had similar reactions to their environment and consequently showed
      similar patterns of brain activity. We discuss the functional resemblance between
      linkage, as an indicator of a shared physiology and affect, and the well-known
      mirror neuron system, and how they relate to social functions like empathy.

PMID- 24278113
TI  - Idraparinux or idrabiotaparinux for long-term venous thromboembolism treatment: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a prevalent disease with potential
      serious consequences. Idraparinux and idrabiotaparinux are two kinds of long
      acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux
      are effective anticoagulants. However, up to now, there is no consensus on
      whether they are better than other anticoagulation methods for long-term VTE
      treatment. OBJECTIVE: To evaluate the effect of idraparinux or idrabiotaparinux
      versus other anticoagulation methods for long-term VTE treatment. METHODS: We
      searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of
      science, clinical trial registry web sites (clinical trials,WHO clinical trial
      registry), Googlescholar, PubMed related articles and companies' web sites
      electronically up to Dec 30(th), 2012 and manually searched the reference lists
      and conference proceedings. Only randomized controlled trial (RCT) involving
      adult patients comparing idraparinux and/or idrabiotaparinux versus other
      anticoagulation methods for long-term VTE treatment was included. Two reviewers
      evaluated the studies and extracted data independently. Pooled risk ratios (RRs)
      were calculated as outcome measures and Revman 5.2 software was used to analyze
      data. Our primary efficacy and safety outcomes were the recurrent VTE and major
      bleeding rates. RESULTS: We included four RCTs and involved 8584 participants on
      idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from
      9364 references. We did not perform meta-analysis on the VTE rate because of the
      significant heterogeneity. We used the fixed effect model to analyze the safety
      outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major
      bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a
      trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P =
      0.05) compared with warfarin. CONCLUSIONS: Until now there is not sufficient
      evidence to clarify whether idraparinux or idrabiotaparinux is as effective and
      safe as the standard warfarin treatment for VTE treatment.

PMID- 24278114
TI  - A process similar to autophagy is associated with cytocidal chloroquine
      resistance in Plasmodium falciparum.
AB  - Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ)
      is becoming well understood, however, resistance to cytocidal effects of CQ is
      largely unexplored. We find that PfCRT mutations that almost fully recapitulate
      P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift,
      account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50
      shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine
      sensitive (CQS; strain HB3)*chloroquine resistant (CQR; strain Dd2) genetic cross
      identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes,
      including identification of novel interacting chromosomal loci that influence CQ
      LD50. Candidate genes in these loci are consistent with a role for autophagy in
      CQR(CC), leading us to directly examine the autophagy pathway in
      intraerythrocytic CQR parasites. Indirect immunofluorescence of RBC infected with
      synchronized CQS vs CQR trophozoite stage parasites reveals differences in the
      distribution of the autophagy marker protein PfATG8 coinciding with CQR(CC).
      Taken together, the data show that an unusual autophagy-like process is either
      activated or inhibited for intraerythrocytic trophozoite parasites at LD50 doses
      (but not IC50 doses) of CQ, that the pathway is altered in CQR P. falciparum, and
      that it may contribute along with mutations in PfCRT to confer the CQR(CC)
      phenotype.

PMID- 24278115
TI  - Non-invasive imaging of tumors by monitoring autotaxin activity using an enzyme
      activated near-infrared fluorogenic substrate.
AB  - Autotaxin (ATX), an autocrine motility factor that is highly upregulated in
      metastatic cancer, is a lysophospholipase D enzyme that produces the lipid second
      messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC).
      Dysregulation of the lysolipid signaling pathway is central to the
      pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid
      arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has
      emerged as an important source of biomarkers and therapeutic targets. Herein we
      describe development and validation of a fluorogenic analog of LPC (AR-2) that
      enables visualization of ATX activity in vivo. AR-2 exhibits minimal fluorescence
      until it is activated by ATX, which substantially increases fluorescence in the
      near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In
      mice with orthotopic ATX-expressing breast cancer tumors, ATX activated AR-2
      fluorescence. Administration of AR-2 to tumor-bearing mice showed high
      fluorescence in the tumor and low fluorescence in most healthy tissues with tumor
      fluorescence correlated with ATX levels. Pretreatment of mice with an ATX
      inhibitor selectively decreased fluorescence in the tumor. Together these data
      suggest that fluorescence directly correlates with ATX activity and its tissue
      expression. The data show that AR-2 is a non-invasive and selective tool that
      enables visualization and quantitation of ATX-expressing tumors and monitoring
      ATX activity in vivo. 

PMID- 24278116
TI  - MU-Opioid receptor antibody reveals tissue-dependent specific staining and
      increased neuronal MU-receptor immunoreactivity at the injured nerve trunk in
      mice.
AB  - Neuropathic pain is a debilitating chronic disease often resulting from damage to
      peripheral nerves. Activation of opioid receptors on peripheral sensory neurons
      can attenuate pain without central nervous system side effects. Here we aimed to
      analyze the distribution of neuronal MU-opioid receptors, the most relevant
      opioid receptors in the control of clinical pain, along the peripheral neuronal
      pathways in neuropathy. Hence, following a chronic constriction injury of the
      sciatic nerve in mice, we used immunohistochemistry to quantify the MU-receptor
      protein expression in the dorsal root ganglia (DRG), directly at the injured
      nerve trunk, and at its peripheral endings in the hind paw skin. We also
      thoroughly examined the MU-receptor antibody staining specificity. We found that
      the antibody specifically labeled MU-receptors in human embryonic kidney 293
      cells as well as in neuronal processes of the sciatic nerve and hind paw skin
      dermis, but surprisingly not in the DRG, as judged by the use of MU/delta/kappa
      opioid receptor knockout mice. Therefore, a reliable quantitative analysis of MU
      receptor expression in the DRG was not possible. However, we demonstrate that the
      MU-receptor immunoreactivity was strongly enhanced proximally to the injury at
      the nerve trunk, but was unaltered in paws, on days 2 and 14 following injury.
      Thus, MU-opioid receptors at the site of axonal damage might be a promising
      target for the control of painful neuropathies. Furthermore, our findings suggest
      a rigorous tissue-dependent characterization of antibodies' specificity,
      preferably using knockout animals. 

PMID- 24278117
TI  - Associations of sedentary behavior, sedentary bouts and breaks in sedentary time
      with cardiometabolic risk in children with a family history of obesity.
AB  - BACKGROUND: Although reports in adults suggest that breaks in sedentary time are
      associated with reduced cardiometabolic risk, these findings have yet to be
      replicated in children. PURPOSE: To investigate whether objectively measured
      sedentary behavior, sedentary bouts or breaks in sedentary time are independently
      associated with cardiometabolic risk in a cohort of Canadian children aged 8-11
      years with a family history of obesity. METHODS: Data from 286 boys and 236 girls
      living in Quebec, Canada, with at least one biological parent with obesity
      (QUALITY cohort) were collected from 2005-2008, and analyzed in 2013. Sedentary
      behavior, light and moderate-to-vigorous physical activity were measured over 7
      days using accelerometry. Leisure time computer/video game use and TV viewing
      over the past 7 days were self-reported. Outcomes included waist circumference,
      body mass index Z-score, fasting insulin, fasting glucose, triglycerides, HDL
      cholesterol, C-reactive protein and a continuous cardiometabolic risk score.
      RESULTS: After adjustment for confounders, breaks in sedentary time and the
      number of sedentary bouts lasting 1-4 minutes were associated with reduced
      cardiometabolic risk score and lower BMI Z-score in both sexes (all p<0.05). The
      number of sedentary bouts lasting 5-9 minutes was negatively associated with
      waist circumference in girls only, while the number of bouts lasting 10-14
      minutes was positively associated with fasting glucose in girls, and with BMI Z
      score in boys (all p<0.05). Leisure time computer/video game use was associated
      with increased cardiometabolic risk score and waist circumference in boys, while
      TV viewing was associated with increased cardiometabolic risk, waist
      circumference, and BMI Z-score in girls (all p<0.05). CONCLUSIONS: These results
      suggest that frequent interruptions in sedentary time are associated with a
      favourable cardiometabolic risk profile and highlight the deleterious
      relationship between screen time and cardiometabolic risk among children with a
      family history of obesity.

PMID- 24278118
TI  - The monogenean which lost its clamps.
AB  - Ectoparasites face a daily challenge: to remain attached to their hosts.
      Polyopisthocotylean monogeneans usually attach to the surface of fish gills using
      highly specialized structures, the sclerotized clamps. In the original
      description of the protomicrocotylid species Lethacotyle fijiensis, described 60
      years ago, the clamps were considered to be absent but few specimens were
      available and this observation was later questioned. In addition, genera within
      the family Protomicrocotylidae have either clamps of the "gastrocotylid" or the
      "microcotylid" types; this puzzled systematists because these clamp types are
      characteristic of distinct, major groups. Discovery of another, new, species of
      the genus Lethacotyle, has allowed us to explore the nature of the attachment
      structures in protomicrocotylids. Lethacotyle vera n. sp. is described from the
      gills of the carangid Caranx papuensis off New Caledonia. It is distinguished
      from Lethacotyle fijiensis, the only other species of the genus, by the length of
      the male copulatory spines. Sequences of 28S rDNA were used to build a tree, in
      which Lethacotyle vera grouped with other protomicrocotylids. The identity of the
      host fish was confirmed with COI barcodes. We observed that protomicrocotylids
      have specialized structures associated with their attachment organ, such as
      lateral flaps and transverse striations, which are not known in other
      monogeneans. We thus hypothesized that the clamps in protomicrocotylids were
      sequentially lost during evolution, coinciding with the development of other
      attachment structures. To test the hypothesis, we calculated the surfaces of
      clamps and body in 120 species of gastrocotylinean monogeneans, based on
      published descriptions. The ratio of clamp surface: body surface was the lowest
      in protomicrocotylids. We conclude that clamps in protomicrocotylids are
      vestigial organs, and that occurrence of "gastrocotylid" and simpler
      "microcotylid" clamps within the same family are steps in an evolutionary
      sequence, leading to the absence of these attributes in species of Lethacotyle.

PMID- 24278119
TI  - Group membership affects spontaneous mental representation: failure to represent
      the out-group in a joint action task.
AB  - Predicting others' actions is crucial to successful social interaction. Previous
      research on joint action, based on a reaction-time paradigm called the Joint
      Simon Task, suggests that successful joint action stems from the simultaneous
      representation of the self with the other. Performance on this task provides a
      read-out of the degree of intrusion from a partner that participants experience
      from acting jointly compared to acting alone, which in turn is a measure of the
      degree to which participants mentally represent their co-actors during the task.
      To investigate the role of perceived group membership in this type of joint
      action and its influence on the representation of others, we first subjected
      participants to a minimal group paradigm while manipulating differences in social
      competition. We then asked participants to do the Joint Simon Task in pairs with
      an in-group or out-group member. Only participants who acted with an "in-group"
      partner on the joint task showed altered reaction times compared to when acting
      alone, presumably a change caused by the simultaneous and automatic
      representation of their in-group partner. In contrast, participants who acted
      with an out-group partner were unaffected in their reactions when doing the joint
      task, showing no evidence of representation of their out-group partner. This
      effect was present in both the high-competition and low-competition conditions,
      indicating that the differential effects of group membership on representation
      during joint action were driven by perceived group membership and independent of
      the effects of social competition. We concluded that participants failed to
      represent out-group members as socially relevant agents not based on any
      personality or situational characteristics, but in reaction only to their status
      as "other". In this way group membership appears to affect cognition on a very
      immediate and subconscious level. 

PMID- 24278120
TI  - Cytokines and tumor metastasis gene variants in oral cancer and precancer in
      Puerto Rico.
AB  - OBJECTIVES: A cross-sectional epidemiological study explored genetic
      susceptibility to oral precancer and cancer in Puerto Rico (PR). MATERIALS AND
      METHODS: Three hundred three individuals with a benign oral condition, oral
      precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial
      dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR
      pathology laboratories. A standardized, structured questionnaire obtained
      information on epidemiological variables; buccal cells were collected for genetic
      analysis. Genotyping was performed using Taqman(r) assays. Allelic frequencies of
      single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes
      influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or
      SCCA while having a variant allele were generated using logistic regression.
      Adjusted models controlled for age, gender, ancestry, education, smoking and
      alcohol consumption. RESULTS: Relative to persons with a benign oral lesion,
      individuals with homozygous recessive allelic variants of tumor necrosis factor
      (TNF-alpha) -238 A/G SNP had a reduced odds of having an oral precancer
      (ORadjusted = 0.15; 95% CI 0.03-0.70). The transforming growth factor beta-1
      (TGFbeta-1 -509 C/T) polymorphism was inversely associated with having an oral
      SCCA among persons homozygous for the recessive variant (ORcrude = 0.27; 95% CI
      0.09-0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was
      associated with oral SCCA; participants with even one variant allele were more
      likely to have oral SCCA (ORadjusted = 2.62, 95% CI 1.05-6.53) compared to people
      with ancestral alleles. CONCLUSION: Our exploratory analyses suggest that genetic
      alterations in immune system genes and genes with metastatic potential are
      associated with oral precancer and SCCA risk in PR.

PMID- 24278121
TI  - The internet as a mental health advisor in Germany--results of a national survey.
AB  - The internet constitutes a popular source of health information. However, the use
      of the internet and other modern media in the domain of mental health remains
      widely unclear. This study aimed at exploring the readiness for seeking
      information online and making use of online counseling and media-assisted
      psychotherapy. A representative survey of N = 2411 Germans was conducted. Results
      indicated that more than one fourth of Germans would consider seeking help online
      in case of psychic strain. Participants reported that they would use the internet
      when needing to research about mental health topics and to communicate with
      persons concerned on internet forums. Only a small number of participants had
      already used psychological online-counseling. The majority of subjects reported
      not having known about the possibility of online counseling. However, the
      willingness to make use of this option in the future was in a medium range.
      Concerning the treatment of mental disorders, participants showed a clear
      preference toward conventional face-to-face treatment. Less than 10% of
      participants considered the use of treatment supported by mobile phones, the
      internet, or virtual realities as likely. Certainly, readiness was significantly
      higher in persons who were already using the relevant devices--mobile phones,
      computers, and the internet. In the future, there will presumably be an
      increasing demand for media-assisted psychological counseling and interventions.
      Members of the health care system should therefore prepare for current
      developments and help enlighten patients with regard to the possibilities, and
      also the potential risks of e-mental health.

PMID- 24278122
TI  - Change in BMI accurately predicted by social exposure to acquaintances.
AB  - Research has mostly focused on obesity and not on processes of BMI change more
      generally, although these may be key factors that lead to obesity. Studies have
      suggested that obesity is affected by social ties. However these studies used
      survey based data collection techniques that may be biased toward select only
      close friends and relatives. In this study, mobile phone sensing techniques were
      used to routinely capture social interaction data in an undergraduate dorm. By
      automating the capture of social interaction data, the limitations of self
      reported social exposure data are avoided. This study attempts to understand and
      develop a model that best describes the change in BMI using social interaction
      data. We evaluated a cohort of 42 college students in a co-located university
      dorm, automatically captured via mobile phones and survey based health-related
      information. We determined the most predictive variables for change in BMI using
      the least absolute shrinkage and selection operator (LASSO) method. The selected
      variables, with gender, healthy diet category, and ability to manage stress, were
      used to build multiple linear regression models that estimate the effect of
      exposure and individual factors on change in BMI. We identified the best model
      using Akaike Information Criterion (AIC) and R(2). This study found a model that
      explains 68% (p<0.0001) of the variation in change in BMI. The model combined
      social interaction data, especially from acquaintances, and personal health
      related information to explain change in BMI. This is the first study taking into
      account both interactions with different levels of social interaction and
      personal health-related information. Social interactions with acquaintances
      accounted for more than half the variation in change in BMI. This suggests the
      importance of not only individual health information but also the significance of
      social interactions with people we are exposed to, even people we may not
      consider as close friends. 

PMID- 24278123
TI  - Density of wild prey modulates lynx kill rates on free-ranging domestic sheep.
AB  - Understanding the factors shaping the dynamics of carnivore-livestock conflicts
      is vital to facilitate large carnivore conservation in multi-use landscapes. We
      investigated how the density of their main wild prey, roe deer Capreolus
      capreolus, modulates individual Eurasian lynx Lynx lynx kill rates on free
      ranging domestic sheep Ovis aries across a range of sheep and roe deer densities.
      Lynx kill rates on free-ranging domestic sheep were collected in south-eastern
      Norway from 1995 to 2011 along a gradient of different livestock and wild prey
      densities using VHF and GPS telemetry. We used zero-inflated negative binomial
      (ZINB) models including lynx sex, sheep density and an index of roe deer density
      as explanatory variables to model observed kill rates on sheep, and ranked the
      models based on their AICc values. The model including the effects of lynx sex
      and sheep density in the zero-inflation model and the effect of lynx sex and roe
      deer density in the negative binomial part received most support. Irrespective of
      sheep density and sex, we found the lowest sheep kill rates in areas with high
      densities of roe deer. As roe deer density decreased, males killed sheep at
      higher rates, and this pattern held for both high and low sheep densities.
      Similarly, females killed sheep at higher rates in areas with high densities of
      sheep and low densities of roe deer. However, when sheep densities were low
      females rarely killed sheep irrespective of roe deer density. Our quantification
      of depredation rates can be the first step towards establishing fairer
      compensation systems based on more accurate and area specific estimation of
      losses. This study demonstrates how we can use ecological theory to predict where
      losses of sheep will be greatest, and can be used to identify areas where
      mitigation measures are most likely to be needed. 

PMID- 24278124
TI  - Targeting TNF-alpha and NF-kappaB activation by bee venom: role in suppressing
      adjuvant induced arthritis and methotrexate hepatotoxicity in rats.
AB  - Low dose methotrexate is the cornerstone for the treatment of rheumatoid
      arthritis. One of its major drawbacks is hepatotoxicity, resulting in poor
      compliance of therapy. Dissatisfied arthritis patients are likely to seek the
      option of complementary and alternative medicine such as bee venom. The
      combination of natural products with modern medicine poses the possibility of
      potential interaction between the two groups and needs investigation. The present
      study was aimed to investigate the modulatory effect of bee venom acupuncture on
      efficacy, toxicity, and pharmacokinetics and tissue disposition of methotrexate.
      Complete Freund's adjuvant induced arthritic rats were treated for 3 weeks with
      methotrexate and/or bee venom. Arthritic score, ankle diameter, paw volume and
      tissue expression of NF-kappaB and TNF-alpha were determined to assess anti
      arthritic effects, while anti-nociceptive effects were assessed by gait score and
      thermal hyperalgesia. Methotrexate toxicity was assessed by measuring serum TNF
      alpha, liver enzymes and expression of NF-kappaB in liver. Combination therapy of
      bee venom with methotrexate significantly improved arthritic parameters and
      analgesic effect as compared to methotrexate alone. Bee venom ameliorated serum
      TNF-alpha and liver enzymes elevations as well as over expression of NF-kappaB in
      liver induced by methotrexate. Histological examination supported the results.
      And for the first time bee venom acupuncture was approved to increase
      methotrexate bioavailability with a significant decrease in its elimination.
      CONCLUSION: bee venom potentiates the anti-arthritic effects of methotrexate,
      possibly by increasing its bioavailability. Also, it provides a potent anti
      nociceptive effect. Furthermore, bee venom protects against methotrexate induced
      hepatotoxicity mostly due to its inhibitory effect on TNF-alpha and NF-kappaB.

PMID- 24278125
TI  - The soluble form of the EIAV receptor encoded by an alternative splicing variant
      inhibits EIAV infection of target cells.
AB  - Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for
      equine infectious anemia virus (EIAV) and is a member of the tumor necrosis
      factor receptor (TNFR) superfamily. In addition to the previously described
      membrane-associated form of ELR1, two other major alternative splicing variant
      mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major
      spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a
      premature stop codon situated 561 nt upstream of the predicted membrane spanning
      domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a
      shift of the open reading frame and generates a stop codon 312 nt downstream.
      Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN
      was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN
      was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1,
      the transcription level of ELR1-IN varied among individual horses and at
      different time points in the same individuals. The ratio of ELR1-IN mRNA species
      to ELR1 mRNA was approximately 1?2.5. Pre-incubation of the recombinant sELR1
      with EIAV significantly inhibited EIAV infection in equine macrophages, the
      primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are
      susceptible to EIAV in vitro, and the replication of EIAV in FED cells
      transiently transfected with ELR1-IN was markedly reduced when compared with
      replication in cells transfected with the empty vector. Finally, the expression
      levels of both forms of the EIAV receptor were significantly regulated by
      infection with this virus. Taken together, our data indicate that sELR1 acts as a
      secreted cellular factor that inhibits EIAV infection in host cells. 

PMID- 24278126
TI  - Soothing the threatened brain: leveraging contact comfort with emotionally
      focused therapy.
AB  - Social relationships are tightly linked to health and well-being. Recent work
      suggests that social relationships can even serve vital emotion regulation
      functions by minimizing threat-related neural activity. But relationship distress
      remains a significant public health problem in North America and elsewhere. A
      promising approach to helping couples both resolve relationship distress and
      nurture effective interpersonal functioning is Emotionally Focused Therapy for
      couples (EFT), a manualized, empirically supported therapy that is strongly
      focused on repairing adult attachment bonds. We sought to examine a neural index
      of social emotion regulation as a potential mediator of the effects of EFT.
      Specifically, we examined the effectiveness of EFT for modifying the social
      regulation of neural threat responding using an fMRI-based handholding procedure.
      Results suggest that EFT altered the brain's representation of threat cues in the
      presence of a romantic partner. EFT-related changes during stranger handholding
      were also observed, but stranger effects were dependent upon self-reported
      relationship quality. EFT also appeared to increase threat-related brain activity
      in regions associated with self-regulation during the no-handholding condition.
      These findings provide a critical window into the regulatory mechanisms of close
      relationships in general and EFT in particular. 

PMID- 24278127
TI  - Operationalising factors that explain the emergence of infectious diseases: a
      case study of the human campylobacteriosis epidemic.
AB  - A framework of general factors for infectious disease emergence was made
      operational for Campylobacter utilising explanatory variables including time
      series and risk factor data. These variables were generated using a combination
      of empirical epidemiology, case-case and case-control studies, time series
      analysis, and microbial sub-typing (source attribution, diversity, genetic
      distance) to unravel the changing/emerging aetiology of human campylobacteriosis.
      The study focused on Scotland between 1990-2012 where there was a 75% increase in
      reported cases that included >300% increase in the elderly and 50% decrease in
      young children. During this period there were three phases 1990-2000 a 75% rise
      and a 20% fall to 2006, followed by a 19% resurgence. The rise coincided with
      expansions in the poultry industry, consumption of chicken, and a shift from
      rural to urban cases. The post-2000 fall occurred across all groups apart from
      the elderly and coincided with a drop of the prevalence of Campylobacter in
      chicken and a higher proportion of rural cases. The increase in the elderly was
      associated with uptake of proton pump inhibitors. During the resurgence the
      increase was predominantly in adults and the elderly, again there was increasing
      use of PPIs and high prevalences in chicken and ruminants. Cases associated with
      foreign travel during the study also increased from 9% to a peak of 16% in 2006
      before falling to an estimated 10% in 2011, predominantly in adults and older
      children. During all three periods source attribution, genetic distance, and
      diversity measurements placed human isolates most similar to those in chickens. A
      combination of emergence factors generic for infectious diseases were responsible
      for the Campylobacter epidemic. It was possible to use these to obtain a putative
      explanation for the changes in human disease and the potential to make an
      informed view of how incidence rates may change in the future. 

PMID- 24278128
TI  - Are chimpanzees really so poor at understanding imperative pointing? Some new
      data and an alternative view of canine and ape social cognition.
AB  - There is considerable interest in comparative research on different species'
      abilities to respond to human communicative cues such as gaze and pointing. It
      has been reported that some canines perform significantly better than monkeys and
      apes on tasks requiring the comprehension of either declarative or imperative
      pointing and these differences have been attributed to domestication in dogs.
      Here we tested a sample of chimpanzees on a task requiring comprehension of an
      imperative request and show that, though there are considerable individual
      differences, the performance by the apes rival those reported in pet dogs. We
      suggest that small differences in methodology can have a pronounced influence on
      performance on these types of tasks. We further suggest that basic differences in
      subject sampling, subject recruitment and rearing experiences have resulted in a
      skewed representation of canine abilities compared to those of monkeys and apes. 

PMID- 24278129
TI  - Using genes as characters and a parsimony analysis to explore the phylogenetic
      position of turtles.
AB  - The phylogenetic position of turtles within the vertebrate tree of life remains
      controversial. Conflicting conclusions from different studies are likely a
      consequence of systematic error in the tree construction process, rather than
      random error from small amounts of data. Using genomic data, we evaluate the
      phylogenetic position of turtles with both conventional concatenated data
      analysis and a "genes as characters" approach. Two datasets were constructed, one
      with seven species (human, opossum, zebra finch, chicken, green anole, Chinese
      pond turtle, and western clawed frog) and 4584 orthologous genes, and the second
      with four additional species (soft-shelled turtle, Nile crocodile, royal python,
      and tuatara) but only 1638 genes. Our concatenated data analysis strongly
      supported turtle as the sister-group to archosaurs (the archosaur hypothesis),
      similar to several recent genomic data based studies using similar methods. When
      using genes as characters and gene trees as character-state trees with equal
      weighting for each gene, however, our parsimony analysis suggested that turtles
      are possibly sister-group to diapsids, archosaurs, or lepidosaurs. None of these
      resolutions were strongly supported by bootstraps. Furthermore, our incongruence
      analysis clearly demonstrated that there is a large amount of inconsistency among
      genes and most of the conflict relates to the placement of turtles. We conclude
      that the uncertain placement of turtles is a reflection of the true state of
      nature. Concatenated data analysis of large and heterogeneous datasets likely
      suffers from systematic error and over-estimates of confidence as a consequence
      of a large number of characters. Using genes as characters offers an alternative
      for phylogenomic analysis. It has potential to reduce systematic error, such as
      data heterogeneity and long-branch attraction, and it can also avoid problems
      associated with computation time and model selection. Finally, treating genes as
      characters provides a convenient method for examining gene and genome evolution. 

PMID- 24278130
TI  - Detection of patient subgroups with differential expression in omics data: a
      comprehensive comparison of univariate measures.
AB  - Detection of yet unknown subgroups showing differential gene or protein
      expression is a frequent goal in the analysis of modern molecular data.
      Applications range from cancer biology over developmental biology to toxicology.
      Often a control and an experimental group are compared, and subgroups can be
      characterized by differential expression for only a subgroup-specific set of
      genes or proteins. Finding such genes and corresponding patient subgroups can
      help in understanding pathological pathways, diagnosis and defining drug targets.
      The size of the subgroup and the type of differential expression determine the
      optimal strategy for subgroup identification. To date, commonly used software
      packages hardly provide statistical tests and methods for the detection of such
      subgroups. Different univariate methods for subgroup detection are characterized
      and compared, both on simulated and on real data. We present an advanced design
      for simulation studies: Data is simulated under different distributional
      assumptions for the expression of the subgroup, and performance results are
      compared against theoretical upper bounds. For each distribution, different
      degrees of deviation from the majority of observations are considered for the
      subgroup. We evaluate classical approaches as well as various new suggestions in
      the context of omics data, including outlier sum, PADGE, and kurtosis. We also
      propose the new FisherSum score. ROC curve analysis and AUC values are used to
      quantify the ability of the methods to distinguish between genes or proteins with
      and without certain subgroup patterns. In general, FisherSum for small subgroups
      and t-test for large subgroups achieve best results. We apply each method to a
      case-control study on Parkinson's disease and underline the biological benefit of
      the new method.

PMID- 24278131
TI  - Global analysis of differentially expressed genes and proteins in the wheat
      callus infected by Agrobacterium tumefaciens.
AB  - Agrobacterium-mediated plant transformation is an extremely complex and evolved
      process involving genetic determinants of both the bacteria and the host plant
      cells. However, the mechanism of the determinants remains obscure, especially in
      some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated
      transformation. In this study, differentially expressed genes (DEGs) and
      differentially expressed proteins (DEPs) were analyzed in wheat callus cells co
      cultured with Agrobacterium by using RNA sequencing (RNA-seq) and two-dimensional
      electrophoresis (2-DE) in conjunction with mass spectrometry (MS). A set of 4,889
      DEGs and 90 DEPs were identified, respectively. Most of them are related to
      metabolism, chromatin assembly or disassembly and immune defense. After
      comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics
      datasets simultaneously. In addition, real-time RT-PCR experiments were performed
      to check the differential expression of the 24 genes, and the results were
      consistent with the RNA-seq data. According to gene ontology (GO) analysis, we
      found that a big part of these differentially expressed genes were related to the
      process of stress or immunity response. Several putative determinants and
      candidate effectors responsive to Agrobacterium mediated transformation of wheat
      cells were discussed. We speculate that some of these genes are possibly related
      to Agrobacterium infection. Our results will help to understand the interaction
      between Agrobacterium and host cells, and may facilitate developing efficient
      transformation strategies in cereal crops. 

PMID- 24278132
TI  - Methylome analysis and epigenetic changes associated with menarcheal age.
AB  - Reproductive factors have been linked to both breast cancer and DNA methylation,
      suggesting methylation as an important mechanism by which reproductive factors
      impact on disease risk. However, few studies have investigated the link between
      reproductive factors and DNA methylation in humans. Genome-wide methylation in
      peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study
      was investigated using LUminometric Methylation Assay (LUMA). Also, methylation
      of 458877 CpG sites was additionally investigated in an independent group of 332
      participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation
      450 BeadChip. Multivariate logistic regression and linear models were used to
      investigate the association between reproductive risk factors and genome wide and
      CpG-specific DNA methylation, respectively. Menarcheal age was inversely
      associated with global DNA methylation as measured with LUMA. For each yearly
      increase in age at menarche, the risk of having genome wide methylation below
      median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at
      menarche was treated as a categorical variable, there was an inverse dose
      response relationship with LUMA methylation levels (OR(12-14 vs. <=11 yrs):1.78,
      95%CI:1.01-3.17 and OR(>=15 vs. <=11 yrs):4.59, 95%CI:2.04-10.33; P for
      trend<0.0001). However, average levels of global methylation as measured by the
      Illumina technology were not significantly associated with menarcheal age. In
      locus by locus comparative analyses, only one CpG site had significantly
      different methylation depending on the menarcheal age category examined, but this
      finding was not replicated by pyrosequencing in an independent data set. This
      study suggests a link between age at menarche and genome wide DNA methylation,
      and the difference in results between the two arrays suggests that repetitive
      element methylation has a role in the association. Epigenetic changes may be
      modulated by menarcheal age, or the association may be a mirror of other
      important changes in early life that have a detectable effect on both methylation
      levels and menarcheal age.

PMID- 24278133
TI  - Taurolidine lock solutions for the prevention of catheter-related bloodstream
      infections: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are a significant
      cause of morbidity and mortality in critically ill patients, contributing to
      prolonged hospital stays and increased costs. Whether taurolidine lock solutions
      (TLS) are beneficial for the prevention of CRBSIs remains controversial. In this
      meta-analysis, we aim to assess the efficacy of TLS for preventing CRBSIs.
      METHODS: We conducted a systematic search of PubMed, EMBASE, and the Cochrane
      Central Register of Controlled Trials. Eligible studies included randomized
      controlled trials that reported on the effects of TLS for preventing CRBSIs. The
      primary outcome in these studies was catheter-related bloodstream infections,
      with microbial distribution of CRBSI and catheter-associated thrombosis as
      secondary outcomes. Data were combined using random-effects models owing to
      significant clinical heterogeneity. RESULTS: Six randomized controlled trials
      (RCTs) conducted from 2004 through 2013 involving 431 patients and 86,078
      catheter-days were included in the review. TLS were significantly associated with
      a lower incidence of CRBSIs when compared to heparin lock solutions (Risk Ratio
      [RR], 0.34; 95% Confidence Interval [CI], 0.21-0.55). Use of TLS significantly
      decreased the incidence of CRBSIs from gram-negative (G-) bacteria (P = 0.004;
      RR, 0.27; CI, 0.11-0.65), and was associated with a non-significant decrease in
      gram-positive (G+) bacterial infections (P = 0.07; RR, 0.41; CI, 0.15-1.09). No
      significant association was observed with TLS and catheter-associated thrombosis
      (RR, 1.99; CI, 0.75-5.28). CONCLUSIONS: The use of TLS reduced the incidence of
      CRBSIs without obvious adverse effects or bacterial resistance. However, the
      susceptibility of G+ and G- bacteria to taurolidine and the risk for catheter
      associated thrombosis of TLS are indeterminate due to limited data. The results
      should be treated with caution due to the limited sample sizes and methodological
      deficiencies of included studies. Therefore, additional well-designed and
      adequately powered RCTs are needed to confirm these findings.

PMID- 24278134
TI  - Humpback whale song on the Southern Ocean feeding grounds: implications for
      cultural transmission.
AB  - Male humpback whales produce a long, complex, and stereotyped song on low
      latitude breeding grounds; they also sing while migrating to and from these
      locations, and occasionally in high-latitude summer feeding areas. All males in a
      population sing the current version of the constantly evolving display and,
      within an ocean basin, populations sing similar songs; however, this sharing can
      be complex. In the western and central South Pacific region there is repeated
      cultural transmission of song types from eastern Australia to other populations
      eastward. Song sharing is hypothesized to occur through several possible
      mechanisms. Here, we present the first example of feeding ground song from the
      Southern Ocean Antarctic Area V and compare it to song from the two closest
      breeding populations. The early 2010 song contained at least four distinct
      themes; these matched four themes from the eastern Australian 2009 song, and the
      same four themes from the New Caledonian 2010 song recorded later in the year.
      This provides evidence for at least one of the hypothesized mechanisms of song
      transmission between these two populations, singing while on shared summer
      feeding grounds. In addition, the feeding grounds may provide a point of acoustic
      contact to allow the rapid horizontal cultural transmission of song within the
      western and central South Pacific region and the wider Southern Ocean. 

PMID- 24278135
TI  - Differential effects of beta-catenin and NF-kappaB interplay in the regulation of
      cell proliferation, inflammation and tumorigenesis in response to bacterial
      infection.
AB  - Both beta-catenin and NF-kappaB have been implicated in our laboratory as
      candidate factors in driving proliferation in an in vivo model of Citrobacter
      rodentium (CR)-induced colonic crypt hyper-proliferation and hyperplasia. Herein,
      we test the hypothesis that beta-catenin and not necessarily NF-kappaB regulates
      colonic crypt hyperplasia or tumorigenesis in response to CR infection. When
      C57Bl/6 wild type (WT) mice were infected with CR, sequential increases in
      proliferation at days 9 and 12 plateaued off at day 19 and paralleled increases
      in NF-kappaB signaling. In Tlr4(-/-) (KO) mice, a sequential but sustained
      proliferation which tapered off only marginally at day 19, was associated with
      TLR4-dependent and independent increases in NF-kappaB signaling. Similarly,
      increases in either activated or total beta-catenin in the colonic crypts of WT
      mice as early as day 3 post-infection coincided with cyclinD1 and c-myc
      expression and associated crypt hyperplasia. In KO mice, a delayed kinetics
      associated predominantly with increases in non-phosphorylated (active) beta
      catenin coincided with increases in cyclinD1, c-myc and crypt hyperplasia.
      Interestingly, PKCzeta-catalyzed Ser-9 phosphorylation and inactivation of GSK
      3beta and not loss of wild type APC protein accounted for beta-catenin
      accumulation and nuclear translocation in either strain. In vitro studies with
      Wnt2b and Wnt5a further validated the interplay between the Wnt/beta-catenin and
      NF-kappaB pathways, respectively. When WT or KO mice were treated with
      nanoparticle-encapsulated siRNA to beta-catenin (si-beta-Cat), almost complete
      loss of nuclear beta-catenin coincided with concomitant decreases in CD44 and
      crypt hyperplasia without defects in NF-kappaB signaling. si-beta-Cat treatment
      to Apc(Min/+) mice attenuated CR-induced increases in beta-catenin and CD44 that
      halted the growth of mutated crypts without affecting NF-kappaB signaling. The
      predominant beta-catenin-induced crypt proliferation was further validated in a
      Castaneus strain (B6.CAST.11M) that exhibited significant crypt hyperplasia
      despite an attenuated NF-kappaB signaling. Thus, beta-catenin and not necessarily
      NF-kappaB regulates crypt hyperplasia in response to bacterial infection.

PMID- 24278137
TI  - Reliability of three-dimensional pseudo-continuous arterial spin labeling MR
      imaging for measuring visual cortex perfusion on two 3T scanners.
AB  - Cerebral blood flow (CBF) in the human primary visual cortex is correlated with
      the loss of visual function in neuro-ophthalmological diseases. Advanced three
      dimensional pseudo-continuous arterial spin labeling (3D pCASL), as a non
      invasive method to access the CBF, can be a novel measurement to detect the
      visual cortex. The objective of the study was to assess the intra- and inter
      scanner reliability of 3D pCASL of the visual cortex in healthy adults and
      suggest the selection of different post-labeling delay times (PLDs). For this
      reason, 3D pCASL was conducted in two 3.0T MR three times with twelve healthy
      volunteers at an interval of 10-15 days. The 1st and 3rd tests were performed on
      scanner-1, and the 2nd test was performed on scanner-2. The value of the CBF was
      abstracted from the visual cortex with two PLDs. The intra- and inter-scanner
      reliability and reproducibility were evaluated with the intraclass correlation
      coefficient (ICC) and Bland-Altman plots. By estimating the mean value of the CBF
      in the visual cortex, the intra-scanner results demonstrated the higher
      reliability (ICC for PLD = 1.5 second presented at 0.743 compared with 0.829 for
      PLD = 2.5 seconds), and the Bland-Altman plots showed the reproducibility at a
      longer PLD. We conclude that the calibrated 3D pCASL approach provides a highly
      reproducible measurement of the CBF of the visual cortex that can serve as a
      useful quantitative probe for research conducted at multiple centers and for the
      long-term observation of the clinical effects of neuro-opthalmological diseases. 

PMID- 24278136
TI  - Interaction between the NOS3 gene and obesity as a determinant of risk of type 2
      diabetes: the Atherosclerosis Risk in Communities study.
AB  - Endothelial nitric oxide synthase 3 (NOS3) catalyzes the production of nitric
      oxide from L-arginine in endothelial cells. Obesity is a modifiable risk factor
      for diabetes, and obese individuals have been reported to have reduced nitric
      oxide availability compared to controls whose weight is in the normal range.
      Since homozygous carriers of the NOS3 G894T variant are predicted to have
      decreased enzyme activity, the association between NOS3 genotype and type 2
      diabetes, and possible effect modification by body mass index (BMI) were
      evaluated. The prevalence of diabetes and BMI was determined at baseline in
      14,374 participants 45-66 years of age from the prospective biracial population
      based Atherosclerosis Risk in Communities (ARIC) Study of the development of
      atherosclerosis in four communities in the United States. Individuals with a BMI
      >=30 kg/m(2) were considered obese. Those subjects not meeting the case
      definition were the comparison groups for the 728 African American and 980 white
      participants with diabetes. Multivariable logistic regression models adjusted for
      age, sex, and field center were used to test for main genetic effects and
      interaction with obesity. Although the NOS3 G894T variant was not independently
      associated with diabetes in either African Americans or whites, significant
      interaction between BMI and the NOS3 polymorphism indicated that obesity was an
      effect modifier of diabetes risk for white individuals with the TT genotype (odds
      ratio (OR) for interaction = 1.65, p = 0.04). In stratified analyses,
      homozygosity for the NOS3 T allele in obese white participants but not in those
      whose BMI <30 kg/m(2) was associated with an elevated risk of diabetes (OR =
      1.47, p = 0.02) when compared to the common GG genotype. These results suggest
      that interaction between obesity and NOS3 genotype may be a determinant of
      diabetes case status in whites in the ARIC cohort. Replication in other
      populations will be required to confirm these observations. 

PMID- 24278138
TI  - Genetic variation in SULF2 is associated with postprandial clearance of
      triglyceride-rich remnant particles and triglyceride levels in healthy subjects.
AB  - CONTEXT: Nonfasting (postprandial) triglyceride concentrations have emerged as a
      clinically significant cardiovascular disease risk factor that results from
      accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation.
      The remnant TRLs are cleared from the circulation by hepatic uptake, but the
      specific mechanisms involved are unclear. The syndecan-1 heparan sulfate
      proteoglycan (HSPG) pathway is important for the hepatic clearance of remnant
      TRLs in mice, but its relevance in humans is unclear. OBJECTIVE: We sought to
      determine whether polymorphisms of the genes responsible for HSPG assembly and
      disassembly contribute to atherogenic dyslipoproteinemias in humans. PATIENTS AND
      DESIGN: We performed an oral fat load in 68 healthy subjects. Lipoproteins
      (chylomicrons and very low density lipoproteins 1 and 2) were isolated from
      blood, and the area under curve and incremental area under curve for postprandial
      variables were calculated. Single nucleotide polymorphisms in genes encoding
      syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were
      genotyped in the study subjects. RESULTS: Our results indicate that the genetic
      variation rs2281279 in SULF2 associates with postprandial clearance of remnant
      TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279
      in SULF2 associates with hepatic SULF2 mRNA levels. CONCLUSIONS: In humans, mild
      but clinically relevant postprandial hyperlipidemia due to reduced hepatic
      clearance of remnant TRLs may result from genetic polymorphisms that affect
      hepatic HSPG.

PMID- 24278139
TI  - Potential human pathogenic bacteria in a mixed urban watershed as revealed by
      pyrosequencing.
AB  - Current microbial source tracking (MST) methods for water depend on testing for
      fecal indicator bacterial counts or specific marker gene sequences to identify
      fecal contamination where potential human pathogenic bacteria could be present.
      In this study, we applied 454 high-throughput pyrosequencing to identify
      bacterial pathogen DNA sequences, including those not traditionally monitored by
      MST and correlated their abundances to specific sources of contamination such as
      urban runoff and agricultural runoff from concentrated animal feeding operations
      (CAFOs), recreation park area, waste-water treatment plants, and natural sites
      with little or no human activities. Samples for pyrosequencing were surface
      water, and sediment collected from 19 sites. A total of 12,959 16S rRNA gene
      sequences with average length of <=400 bp were obtained, and were assigned to
      corresponding taxonomic ranks using ribosomal database project (RDP), Classifier
      and Greengenes databases. The percent of total potential pathogens were highest
      in urban runoff water (7.94%), agricultural runoff sediment (6.52%), and Prado
      Park sediment (6.00%), respectively. Although the numbers of DNA sequence tags
      from pyrosequencing were very high for the natural site, corresponding percent
      potential pathogens were very low (3.78-4.08%). Most of the potential pathogenic
      bacterial sequences identified were from three major phyla, namely,
      Proteobacteria, Bacteroidetes, and Firmicutes. The use of deep sequencing may
      provide improved and faster methods for the identification of pathogen sources in
      most watersheds so that better risk assessment methods may be developed to
      enhance public health. 

PMID- 24278142
TI  - New fossil Lepidoptera (Insecta: Amphiesmenoptera) from the Middle Jurassic
      Jiulongshan Formation of Northeastern China.
AB  - BACKGROUND: The early history of the Lepidoptera is poorly known, a feature
      attributable to an inadequate preservational potential and an exceptionally low
      occurrence of moth fossils in relevant mid-Mesozoic deposits. In this study, we
      examine a particularly rich assemblage of morphologically basal moths that
      contribute significantly toward the understanding of early lepidopteran
      biodiversity. METHODOLOGY/PRINCIPAL FINDINGS: Our documentation of early fossil
      moths involved light- and scanning electron microscopic examination of specimens,
      supported by various illumination and specimen contrast techniques. A total of 20
      moths were collected from the late Middle Jurassic Jiulongshan Formation in
      Northeastern China. Our principal results were the recognition and description of
      seven new genera and seven new species assigned to the Eolepidopterigidae; one
      new genus with four new species assigned to the Mesokristenseniidae; three new
      genera with three new species assigned to the Ascololepidopterigidae fam. nov.;
      and one specimen unassigned to family. Lepidopteran assignment of these taxa is
      supported by apomorphies of extant lineages, including the M1 vein, after
      separation from the M2 vein, subtending an angle greater than 60 degrees that is
      sharply angulate at the junction with the r-m crossvein (variable in
      Trichoptera); presence of a foretibial epiphysis; the forewing M vein often
      bearing three branches; and the presence of piliform scales along wing veins.
      CONCLUSIONS/SIGNIFICANCE: The diversity of these late Middle Jurassic
      lepidopterans supports a conclusion that the Lepidoptera-Trichoptera divergence
      occurred by the Early Jurassic.

PMID- 24278141
TI  - A generalized measurement model to quantify health: the multi-attribute
      preference response model.
AB  - After 40 years of deriving metric values for health status or health-related
      quality of life, the effective quantification of subjective health outcomes is
      still a challenge. Here, two of the best measurement tools, the discrete choice
      and the Rasch model, are combined to create a new model for deriving health
      values. First, existing techniques to value health states are briefly discussed
      followed by a reflection on the recent revival of interest in patients'
      experience with regard to their possible role in health measurement.
      Subsequently, three basic principles for valid health measurement are reviewed,
      namely unidimensionality, interval level, and invariance. In the main section,
      the basic operation of measurement is then discussed in the framework of
      probabilistic discrete choice analysis (random utility model) and the
      psychometric Rasch model. It is then shown how combining the main features of
      these two models yields an integrated measurement model, called the multi
      attribute preference response (MAPR) model, which is introduced here. This new
      model transforms subjective individual rank data into a metric scale using
      responses from patients who have experienced certain health states. Its
      measurement mechanism largely prevents biases such as adaptation and coping.
      Several extensions of the MAPR model are presented. The MAPR model can be applied
      to a wide range of research problems. If extended with the self-selection of
      relevant health domains for the individual patient, this model will be more valid
      than existing valuation techniques. 

PMID- 24278140
TI  - Factors affecting the prevalence of strongly and weakly carcinogenic and lower
      risk human papillomaviruses in anal specimens in a cohort of men who have sex
      with men (MSM).
AB  - BACKGROUND: MSM are at higher risk for invasive anal cancer. Twelve human
      papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs
      (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical
      malignancy. HPVs rarely associated with malignancy are classified as lower-risk
      HPVs (lrHPVs). MATERIALS AND METHODS: Dacron-swab anal-cytology specimens were
      collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort
      Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate
      Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2
      hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual
      partnerships, smoking; HIV-infection characteristics, treatment, and immune
      status among HIV-infected men. RESULTS: HIV-infected men showed 35-90% higher
      prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher
      prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count
      was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of
      receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV
      testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting >=30
      lifetime male sex partners before their first MACS visit and men reporting >=1
      RAI partners during the 24 months before HPV testing showed 17-24% and 13-17%
      higher prevalence of lrHPVs (p-values <=0.05). Men reporting smoking between MACS
      visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of
      Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV
      load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV
      infected men. CONCLUSIONS: HIV-infected men more often show multi-type and multi
      group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking
      cessation, generally, and CART-adherence that promotes (HIV) viremia control and
      prevents immunosuppression, specifically among HIV-infected MSM, are important
      prevention strategies for HPV infections that are relevant to anal cancer.

PMID- 24278143
TI  - The histone deacetylase inhibitor LBH589 (panobinostat) modulates the crosstalk
      of lymphocytes with Hodgkin lymphoma cell lines.
AB  - Epigenetic changes have been implicated in the malignant phenotype of Hodgkin
      Reed Sternberg (HRS) cells in Hodgkin lymphoma (HL), where HRS survival and
      proliferation depends on the microenvironment. The histone-deacetylase (HDAC)
      inhibitor LBH589 (panobinostat) showed clinical efficacy but its impact on the
      HRS microenvironment is unclear. Hence, we analysed the effects of LBH589 on
      lymphocytes and also potential combination therapies. In lymphocyte-target cell
      killing assays, LBH589-treatment triggered an enhanced lymphocyte-dependent lysis
      of HL cells despite of mild lymphocytopenic effects. In co-culture experiments of
      lymphocytes with HL cells, LBH589 suppressed the IFNgamma-release but increased
      the TNFalpha secretion. Recombinant TNFalpha boosted the lymphocyte-dependent
      lysis of HL target cells. In HL cell lines, LBH589 induced cell death, autophagy,
      and an increase of MICA/B that are ligands to natural killer cell receptors. The
      combination of LBH589 with Brentuximab Vedotin was inefficient due to down
      regulation of CD30 as a target. Combination with gemcitabine revealed highly
      significant effects, suggesting a potential combination for future therapy. Based
      on these data we suggest that LBH589 favourably modulates the cytokine network
      and lymphocyte activity in the HL microenvironment. 

PMID- 24278145
TI  - Selected neurophysiological, psychological, and behavioral influences on
      subjective sleep quality in nurses: a structure equation model.
AB  - Few studies have examined relationships among neurophysiological, psychological,
      and behavioral factors with regard to their effects on sleep quality. We used a
      structure equation model to investigate behavioral and psychological factors that
      influence neurophysiological regulation of sleep in shift workers. Using a cross
      sectional study design, we tested the model with a sample of 338 female nurses
      working rotating shifts at an urban regional hospital. The Morningness
      Eveningness Questionnaire (MEQ) and short-form Menstrual Distress Questionnaire
      (MDQ) were used to measure neurophysiological factors involved in morningness
      eveningness and menstrual distress. The Sleep Hygiene Awareness and Practice
      Scale (SHAPS) and Profile of Mood States Short Form (POMS-SF) were completed to
      measure behavioral factors of sleep hygiene practices and psychological factors
      of mood states. In addition, the Pittsburgh Sleep Quality Index (PSQI) measured
      participant's self-reported sleep quality. The results revealed that sleep
      hygiene practices and mood states mediated the effects of morningness-eveningness
      and menstrual distress on sleep quality. Our findings provide support for
      developing interventions to enhance sleep hygiene and maintain positive mood
      states to reduce the influence of neurophysiological factors on sleep quality
      among shift workers. 

PMID- 24278144
TI  - Changes in bacterial and fungal communities across compost recipes, preparation
      methods, and composting times.
AB  - Compost production is a critical component of organic waste handling, and compost
      applications to soil are increasingly important to crop production. However, we
      know surprisingly little about the microbial communities involved in the
      composting process and the factors shaping compost microbial dynamics. Here, we
      used high-throughput sequencing approaches to assess the diversity and
      composition of both bacterial and fungal communities in compost produced at a
      commercial-scale. Bacterial and fungal communities responded to both compost
      recipe and composting method. Specifically, bacterial communities in manure and
      hay recipes contained greater relative abundances of Firmicutes than hardwood
      recipes with hay recipes containing relatively more Actinobacteria and
      Gemmatimonadetes. In contrast, hardwood recipes contained a large relative
      abundance of Acidobacteria and Chloroflexi. Fungal communities of compost from a
      mixture of dairy manure and silage-based bedding were distinguished by a greater
      relative abundance of Pezizomycetes and Microascales. Hay recipes uniquely
      contained abundant Epicoccum, Thermomyces, Eurotium, Arthrobotrys, and
      Myriococcum. Hardwood recipes contained relatively abundant Sordariomycetes.
      Holding recipe constant, there were significantly different bacterial and fungal
      communities when the composting process was managed by windrow, aerated static
      pile, or vermicompost. Temporal dynamics of the composting process followed known
      patterns of degradative succession in herbivore manure. The initial community was
      dominated by Phycomycetes, followed by Ascomycota and finally Basidiomycota.
      Zygomycota were associated more with manure-silage and hay than hardwood
      composts. Most commercial composters focus on the thermophilic phase as an
      economic means to insure sanitation of compost from pathogens. However, the
      community succeeding the thermophilic phase begs further investigation to
      determine how the microbial dynamics observed here can be best managed to
      generate compost with the desired properties. 

PMID- 24278146
TI  - Agent-based model with asymmetric trading and herding for complex financial
      systems.
AB  - BACKGROUND: For complex financial systems, the negative and positive return
      volatility correlations, i.e., the so-called leverage and anti-leverage effects,
      are particularly important for the understanding of the price dynamics. However,
      the microscopic origination of the leverage and anti-leverage effects is still
      not understood, and how to produce these effects in agent-based modeling remains
      open. On the other hand, in constructing microscopic models, it is a promising
      conception to determine model parameters from empirical data rather than from
      statistical fitting of the results. METHODS: To study the microscopic origination
      of the return-volatility correlation in financial systems, we take into account
      the individual and collective behaviors of investors in real markets, and
      construct an agent-based model. The agents are linked with each other and trade
      in groups, and particularly, two novel microscopic mechanisms, i.e., investors'
      asymmetric trading and herding in bull and bear markets, are introduced. Further,
      we propose effective methods to determine the key parameters in our model from
      historical market data. RESULTS: With the model parameters determined for six
      representative stock-market indices in the world, respectively, we obtain the
      corresponding leverage or anti-leverage effect from the simulation, and the
      effect is in agreement with the empirical one on amplitude and duration. At the
      same time, our model produces other features of the real markets, such as the fat
      tail distribution of returns and the long-term correlation of volatilities.
      CONCLUSIONS: We reveal that for the leverage and anti-leverage effects, both the
      investors' asymmetric trading and herding are essential generation mechanisms.
      Among the six markets, however, the investors' trading is approximately symmetric
      for the five markets which exhibit the leverage effect, thus contributing very
      little. These two microscopic mechanisms and the methods for the determination of
      the key parameters can be applied to other complex systems with similar
      asymmetries.

PMID- 24278147
TI  - Stone throwing as a sexual display in wild female bearded capuchin monkeys,
      Sapajus libidinosus.
AB  - Capuchin monkeys (Sapajus spp.) in captive settings frequently manipulate and
      throw objects. In the wild, they may push or drop stones and sticks toward
      targets during inter- or intraspecific threat displays. In addition, female
      capuchin monkeys exhibit a broad repertoire of behaviors during their proceptive
      period, including facial expressions, vocalizations, stereotyped body postures,
      and touch-and-run behavior. This study reports stone throwing as a newly
      described communicative behavior during the proceptive display of females in a
      group of bearded capuchin monkeys (S. libidinosus) in Serra da Capivara National
      Park, Brazil. During a two-year study, three females from one group were seen
      throwing stones at males during their proceptive phase. After this period, three
      other females in the same group exhibited the same behavior. Although it may be
      possible that this pattern is the result of several independent innovations by
      each female, the apparent absence of this behavior in other groups leads us to
      suggest that we have documented the diffusion of a new behavioral trait or
      tradition within this capuchin social group. 

PMID- 24278148
TI  - Neonatal hyperglycemia inhibits angiogenesis and induces inflammation and
      neuronal degeneration in the retina.
AB  - Recent evidence suggests that transient hyperglycemia in extremely low birth
      weight infants is strongly associated with the occurrence of retinopathy of
      prematurity (ROP). We propose a new model of Neonatal Hyperglycemia-induced
      Retinopathy (NHIR) that mimics many aspects of retinopathy of prematurity.
      Hyperglycemia was induced in newborn rat pups by injection of streptozocine (STZ)
      at post natal day one (P1). At various time points, animals were assessed for
      vascular abnormalities, neuronal cell death and accumulation and activation of
      microglial cells. We here report that streptozotocin induced a rapid and
      sustained increase of glycemia from P2/3 to P6 without affecting rat pups gain
      weight or necessitating insulin treatment. Retinal vascular area was
      significantly reduced in P6 hyperglycemic animals compared to control animals.
      Hyperglycemia was associated with (i) CCL2 chemokine induction at P6, (ii) a
      significant recruitment of inflammatory macrophages and an increase in total
      number of Iba+ macrophages/microglia cells in the inner nuclear layer (INL), and
      (iii) excessive apoptosis in the INL. NHIR thereby reproduces several aspects of
      ischemic retinopathies, including ROP and diabetic retinopathies, and might be a
      useful model to decipher hyperglycemia-induced cellular and molecular mechanisms
      in the small rodent. 

PMID- 24278151
TI  - Assessment of knowledge and practice towards hepatitis B among medical and health
      science students in Haramaya University, Ethiopia.
AB  - INTRODUCTION: Hepatitis B (HB) is a serious infection that affects liver and
      caused by hepatitis B virus (HBV). HB is a serious global public health problem
      and the health professionals are most at risk. It is contagious and easy to be
      transmitted from one infected individual to another by blood to blood contact,
      mother to child, unprotected sexual intercourse, sharing of eating utensils and
      other barber shop and beauty salon equipment. The aim of this study was to assess
      knowledge and practices about transmissions and prevention of hepatitis B among
      medical and health science students on clinical attachment in Haramaya
      University. METHODS AND FINDINGS: A cross sectional study was conducted among 322
      health science and medical students who are starting clinical attachment (year
      II, III, IV, V and IV) from February 1-15, 2013. Self-administered structured
      questionnaire was used to collect information. Out of 322 distributed
      questionnaires, 322 were returned with a response rate of 100.0%. Majority of the
      students (91%) were in the age group 20-24 and 232 (72%) of the respondents were
      male. Majorities (95.3%) of students were not fully vaccinated against Hepatitis
      B and 48.4% of the students were not aware about the availability of post
      exposure prophylaxis for HB. Mean scores for knowledge and practice were 11.52+/
      2.37 and 2.76+/-1.1 respectively. Significant and positive linear correlations
      between knowledge-practice (r = 0.173, p = 0.002) was observed. Study department
      was significantly associated with mean knowledge and practice of study
      respondents. CONCLUSION: This study indicates that lack of awareness about
      Hepatitis B, its route of transmission and modes of prevention among the medical
      students entering into the profession. Similarly, 95.3% the students were not
      fully vaccinated against Hepatitis B, which makes them vulnerable to the disease.

PMID- 24278152
TI  - Directly observed therapy reduces tuberculosis-specific mortality: a population
      based follow-up study in Taipei, Taiwan.
AB  - OBJECTIVES: To determine the effect of directly observed therapy (DOT) on
      tuberculosis-specific mortality and non-TB-specific mortality and identify
      prognostic factors associated with mortality among adults with culture-positive
      pulmonary TB (PTB). METHODS: All adult Taiwanese with PTB in Taipei, Taiwan were
      included in a retrospective cohort study in 2006-2010. Backward stepwise
      multinomial logistic regression was used to identify risk factors associated with
      each mortality outcome. RESULTS: Mean age of the 3,487 patients was 64.2 years
      and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific
      causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on
      SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific
      causes. , After adjustment for potential confounders, the odds ratio for TB
      specific mortality was 0.45 (95% CI: 0.30-0.69) among patients treated with DOT
      as compared with those on self-administered treatment. Independent predictors of
      TB-specific and non-TB-specific mortality included older age (ie, 65-79 and >=80
      years vs. 18-49 years), being unemployed, a positive sputum smear for acid-fast
      bacilli, and TB notification from a general ward or intensive care unit
      (reference: outpatient services). Male sex, end-stage renal disease requiring
      dialysis, malignancy, and pleural effusion on chest radiography were associated
      with increased risk of non-TB-specific mortality, while presence of lung cavities
      on chest radiography was associated with lower risk. CONCLUSIONS: DOT reduced TB
      specific mortality by 55% among patients with PTB, after controlling for
      confounders. DOT should be given to all TB patients to further reduce TB-specific
      mortality.

PMID- 24278150
TI  - Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in
      healthy women: an ERP analysis.
AB  - A working model of the neurophysiology of hypnosis suggests that highly
      hypnotizable individuals (HHs) have more effective frontal attentional systems
      implementing control, monitoring performance, and inhibiting unwanted stimuli
      from conscious awareness, than low hypnotizable individuals (LHs). Recent
      studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR),
      suggest that HHs, in the waking condition, may show reduced sensory gating
      although they may selectively attend and disattend different stimuli. Using a
      within subject design and a strict subject selection procedure, in waking and
      hypnosis conditions we tested whether HHs compared to LHs showed a significantly
      lower inhibition of the ASR and startle-related brain activity in both time and
      intracerebral source localization domains. HHs, as compared to LH participants,
      exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100
      responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the
      P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and
      greater PPI of this component than in the waking condition. sLORETA analysis
      revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a
      smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses
      of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec)
      wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The
      present results, on the whole, are in the opposite direction to PPI findings on
      hypnotizability previously reported in the literature. These results provide
      support to the neuropsychophysiological model that HHs have more effective
      sensory integration and gating (or filtering) of irrelevant stimuli than LHs. 

PMID- 24278149
TI  - Association between microRNA polymorphisms and cancer risk based on the findings
      of 66 case-control studies.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in
      diverse biological processes and may regulate tumor suppressor genes or
      oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to
      diverse functional consequences, including cancer development, by altering miRNA
      expression. Numerous studies have shown the association between miRNA SNPs and
      cancer risk; however, the results are generally debatable and inconclusive,
      mainly due to limited statistical power. To assess the relationship between the
      five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499
      rs3746444, miR-149 rs2292832, and miR-27a rs895919) and the risk cancer
      development, we performed a meta-analysis of 66 published case-control studies.
      Crude odds ratios at 95% confidence intervals were used to investigate the
      strength of the association. No association was observed between rs2910164 and
      cancer risk in the overall group. However, in stratified analysis, we found that
      either the rs2910164 C allele or the CC genotype was protective against bladder
      cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a
      risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the
      head and neck (SCCHN). Further, rs11614913 was found to be significantly
      associated with decreased cancer risk, in particular, for bladder cancer, gastric
      cancer, and SCCHN. For miR-499, a significant association was found between the
      rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis,
      similar results were mainly observed for breast cancer. Finally, no association
      was found between rs2292832 and rs895919 polymorphisms and cancer risk in the
      overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR
      146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development,
      whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer
      risk. 

PMID- 24278153
TI  - Statistical experimental design guided optimization of a one-pot biphasic
      multienzyme total synthesis of amorpha-4,11-diene.
AB  - In vitro synthesis of chemicals and pharmaceuticals using enzymes is of
      considerable interest as these biocatalysts facilitate a wide variety of
      reactions under mild conditions with excellent regio-, chemo- and
      stereoselectivities. A significant challenge in a multi-enzymatic reaction is the
      need to optimize the various steps involved simultaneously so as to obtain high
      yield of a product. In this study, statistical experimental design was used to
      guide the optimization of a total synthesis of amorpha-4,11-diene (AD) using
      multienzymes in the mevalonate pathway. A combinatorial approach guided by
      Taguchi orthogonal array design identified the local optimum enzymatic activity
      ratio for Erg12:Erg8:Erg19:Idi:IspA to be 100?100?1?25?5, with a constant
      concentration of amorpha-4,11-diene synthase (Ads, 100 mg/L). The model also
      identified an unexpected inhibitory effect of farnesyl pyrophosphate synthase
      (IspA), where the activity was negatively correlated with AD yield. This was due
      to the precipitation of farnesyl pyrophosphate (FPP), the product of IspA.
      Response surface methodology was then used to optimize IspA and Ads activities
      simultaneously so as to minimize the accumulation of FPP and the result showed
      that Ads to be a critical factor. By increasing the concentration of Ads, a
      complete conversion (~100%) of mevalonic acid (MVA) to AD was achieved.
      Monovalent ions and pH were effective means of enhancing the specific Ads
      activity and specific AD yield significantly. The results from this study
      represent the first in vitro reconstitution of the mevalonate pathway for the
      production of an isoprenoid and the approaches developed herein may be used to
      produce other isopentenyl pyrophosphate (IPP)/dimethylallyl pyrophosphate (DMAPP)
      based products. 

PMID- 24278154
TI  - Foraging behaviour and landscape utilisation by the endangered golden-crowned
      flying fox (Acerodon jubatus), the Philippines.
AB  - Species of Old World fruit-bats (family Pteropodidae) have been identified as the
      natural hosts of a number of novel and highly pathogenic viruses threatening
      livestock and human health. We used GPS data loggers to record the nocturnal
      foraging movements of Acerodon jubatus, the Golden-crowned flying fox in the
      Philippines to better understand the landscape utilisation of this iconic
      species, with the dual objectives of pre-empting disease emergence and supporting
      conservation management. Data loggers were deployed on eight of 54 A. jubatus
      (two males and six females) captured near Subic Bay on the Philippine island of
      Luzon between 22 November and 2 December 2010. Bodyweight ranged from 730 g to
      1002 g, translating to a weight burden of 3-4% of bodyweight. Six of the eight
      loggers yielded useful data over 2-10 days, showing variability in the nature and
      range of individual bat movements. The majority of foraging locations were in
      closed forest and most were remote from evident human activity. Forty-six
      discrete foraging locations and five previously unrecorded roost locations were
      identified. Our findings indicate that foraging is not a random event, with the
      majority of bats exhibiting repetitious foraging movements night-to-night, that
      apparently intact forest provides the primary foraging resource, and that known
      roost locations substantially underestimate the true number (and location) of
      roosts. Our initial findings support policy and decision-making across
      perspectives including landscape management, species conservation, and
      potentially disease emergence. 

PMID- 24278155
TI  - Rapid molecular testing for TB to guide respiratory isolation in the U.S.: a cost
      benefit analysis.
AB  - BACKGROUND: Respiratory isolation of inpatients during evaluation for TB is a
      slow and costly process in low-burden settings. Xpert MTB/RIF (Xpert) is a novel
      molecular test for tuberculosis (TB) that is faster and more sensitive but
      substantially more expensive than smear microscopy. No previous studies have
      examined the costs of molecular testing as a replacement for smear microscopy in
      this setting. METHODS: We conducted an incremental cost-benefit analysis
      comparing the use of a single negative Xpert versus two negative sputum smears to
      release consecutive adult inpatients with presumed TB from respiratory isolation
      at an urban public hospital in the United States. We estimated all health-system
      costs and patient outcomes related to Xpert implementation, diagnostic
      evaluation, isolation, hospitalization, and treatment. We performed sensitivity
      and probabilistic uncertainty analyses to determine at what threshold the Xpert
      strategy would become cost-saving. RESULTS: Among a hypothetical cohort of 234
      individuals undergoing evaluation for presumed active TB annually, 6.4% had
      culture-positive TB. Compared to smear microscopy, Xpert reduced isolation bed
      utilization from an average of 2.7 to 1.4 days per patient, leading to a 48%
      reduction in total annual isolation bed usage from 632 to 328 bed-days. Xpert
      saved an average of $2,278 (95% uncertainty range $1582-4570) per admission, or
      $533,520 per year, compared with smear microscopy. CONCLUSIONS: Molecular testing
      for TB could provide substantial savings to hospitals in high-income countries by
      reducing respiratory isolation usage and overall length of stay.

PMID- 24278156
TI  - Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
AB  - The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and
      other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II
      has been associated with several complex diseases. In this study we focus on MHC
      haplotype structures in the Finnish population. We explore the variability of
      extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a
      selected group of MHC class III genes. A total of 150 healthy Finnish individuals
      were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, 
      DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA
      genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B
      gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were
      analysed with quantitative genomic realtime-PCR. The allele frequencies for each
      locus were calculated and haplotypes were constructed using both the traditional
      HLA alleles and SNP blocks. The most frequent Finnish A~B~DR -haplotype, uncommon
      in elsewhere in Europe, was A*03~B*35~DRB1*01?01. The second most common
      haplotype was a common European ancestral haplotype AH 8.1
      (A*01~B*08~DRB1*03?01). Extended haplotypes containing HLA-B, TNF block, C4 and
      HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability
      in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and
      HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show
      that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is
      advantageous when studying the polymorphisms and LD patters of the MHC region.
      For disease association studies the HLA-DRB1 haplotypes with various MHC markers
      allows us to cluster haplotypes with functionally important gene variants such as
      C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further
      assessment. Our study corroborates the importance of studying population-specific
      MHC haplotypes. 

PMID- 24278157
TI  - Tuberculosis incidence in HIV/AIDS patients in Israel, 1983-2010.
AB  - OBJECTIVES: People living with HIV/AIDS (PLWHA) who develop tuberculosis disease
      are at greater mortality-risk. This study aimed to assess tuberculosis disease
      incidence among all PLWHA in Israel and identify populations at high-risk for
      developing tuberculosis. DESIGN AND METHODS: Retrospective cohort-study based on
      the National HIV and Tuberculosis Registries, which were cross-matched and
      followed for the last 28-years. PLWHA who developed tuberculosis were compared to
      those who did not by the Cox-proportional analysis to generate hazard-ratios, and
      survival-analysis was performed by Log-Rank test. RESULTS: Of all the 6579 PLWHA
      reported between 1983 and 2010, corresponding to 55737 person-years, 384 (5.8%)
      developed tuberculosis. Of those, 14 were Israeli-born and 370 were non-Israeli
      born. The overall tuberculosis incidence-density was 6.9 cases/1000 person-years
      (95% CI 1.8-12.0). The cumulative tuberculosis-incidence among PLWHA in 2010 was
      586 times higher than in HIV-negative individuals (3400 and 5.8 cases per 100000
      population, respectively). Higher hazard-ratios to developing tuberculosis were
      found in migrant citizens PLWHA who were males, non-Israeli born, those who were
      diagnosed with HIV/AIDS after 1997, those who originated in high-tuberculosis
      prevalence country and those who acquired HIV by heterosexual or drug-injection
      transmission. PLWHA who developed tuberculosis had higher odds of dying than
      other PLWHA (36.5% and 16.6%, respectively, p<0.001, odds ratio = 2.8, 95%
      confidence-interval 2.3-3.6). In survival-analysis, time to develop tuberculosis
      was shorter among males than females, in PLWHA who were reported with HIV after
      1997, in heterosexual who originated in high-tuberculosis countries, followed by
      injecting drug-users, heterosexual from low-tuberculosis burden countries and men
      who have sex with men. CONCLUSION: Tuberculosis-incidence is higher among non
      Israeli born PLWHA, with decreasing trends from 1991. Despite the moderate TB
      rate disease among PLWHA, it remains an important cause for severe morbidity and
      mortality. Tuberculosis in PLWHA reflects mainly the tuberculosis-burden in the
      originating country and possibly also the mode of HIV-transmission.

PMID- 24278158
TI  - Soil bacterial community shifts after chitin enrichment: an integrative
      metagenomic approach.
AB  - Chitin is the second most produced biopolymer on Earth after cellulose. Chitin
      degrading enzymes are promising but untapped sources for developing novel
      industrial biocatalysts. Hidden amongst uncultivated micro-organisms, new
      bacterial enzymes can be discovered and exploited by metagenomic approaches
      through extensive cloning and screening. Enrichment is also a well-known
      strategy, as it allows selection of organisms adapted to feed on a specific
      compound. In this study, we investigated how the soil bacterial community
      responded to chitin enrichment in a microcosm experiment. An integrative
      metagenomic approach coupling phylochips and high throughput shotgun
      pyrosequencing was established in order to assess the taxonomical and functional
      changes in the soil bacterial community. Results indicate that chitin enrichment
      leads to an increase of Actinobacteria, gamma-proteobacteria and beta
      proteobacteria suggesting specific selection of chitin degrading bacteria
      belonging to these classes. Part of enriched bacterial genera were not yet
      reported to be involved in chitin degradation, like the members from the
      Micrococcineae sub-order (Actinobacteria). An increase of the observed bacterial
      diversity was noticed, with detection of specific genera only in chitin treated
      conditions. The relative proportion of metagenomic sequences related to chitin
      degradation was significantly increased, even if it represents only a tiny
      fraction of the sequence diversity found in a soil metagenome. 

PMID- 24278160
TI  - The dual effects of critical thinking disposition on worry.
AB  - This study investigated the relationship between disposition (people's consistent
      motivation) toward critical thinking (CT) and worrying. In spite of its
      connection to psychopathology, worry is thought to represent an effort at problem
      solving. Moreover, worry has been found to be underpinned by cognitive
      development, leading us to predict a positive relationship between worry and CT
      disposition. On the other hand, cognitive behavioral therapy, which involves
      techniques similar to CT, has been shown to be effective in reducing worrying,
      suggesting that increasing CT disposition decreases worrying. This study
      attempted to reconcile these seemingly contrasting predictions about the
      relationship between CT disposition and worrying by using multiple mediator
      analysis. A model was proposed wherein the mediators, responsibility to continue
      thinking and detached awareness of negative thinking, were related to two
      opposing predictions. The former is thought to lead to enhanced worrying and the
      latter to reduced worrying, with both positively related to CT disposition. A
      questionnaire study with university students (N = 760) revealed that CT
      disposition enhanced worrying by obliging people to continue thinking about a
      problem, but that it also reduced worrying by enhancing the detached and
      objective awareness of their negative thoughts. This study thus demonstrated the
      dual effects of CT disposition on worrying through different mediators. Thus,
      when enhancing CT disposition, it is important for educators to be aware of
      possible disadvantages apart from its worry-reducing effect. Future studies
      should therefore examine the underlying mechanisms of these two effects of CT
      disposition. 

PMID- 24278161
TI  - Clinical significance of methicillin-resistant Staphylococcus aureus colonization
      on hospital admission: one-year infection risk.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization
      among inpatients is a well-established risk factor for MRSA infection during the
      same hospitalization, but the long-term risk of MRSA infection is uncertain. We
      performed a retrospective cohort study to determine the one-year risk of MRSA
      infection among inpatients with MRSA-positive nasal polymerase chain reaction
      (PCR) tests confirmed by positive nasal culture (Group 1), patients with positive
      nasal PCR but negative nasal culture (Group 2), and patients with negative nasal
      PCR (Group 3). METHODOLOGY/PRINCIPAL FINDINGS: Subjects were adults admitted to a
      four-hospital system between November 1, 2006 and March 31, 2011, comprising
      195,255 admissions. Patients underwent nasal swab for MRSA PCR upon admission; if
      positive, nasal culture for MRSA was performed; if recovered, MRSA was tested for
      Panton-Valentine Leukocidin (PVL). Outcomes included MRSA-positive clinical
      culture and skin and soft tissue infection (SSTI). Group 1 patients had a one
      year risk of MRSA-positive clinical culture of 8.0% compared with 3.0% for Group
      2 patients, and 0.6% for Group 3 patients (p<0.001). In a multivariable model,
      the hazard ratios for future MRSA-positive clinical culture were 6.52 (95% CI,
      5.57 to 7.64) for Group 1 and 3.40 (95% CI, 2.70 to 4.27) for Group 2, compared
      with Group 3 (p<0.0001). History of MRSA and concurrent MRSA-positive clinical
      culture were significant risk factors for future MRSA-positive clinical culture.
      Group 1 patients colonized with PVL-positive MRSA had a one-year risk of MRSA
      positive clinical culture of 10.1%, and a one-year risk of MRSA-positive clinical
      culture or SSTI diagnosis of 21.7%, compared with risks of 7.1% and 12.5%,
      respectively, for patients colonized with PVL-negative MRSA (p = 0.04, p = 0.005,
      respectively). CONCLUSIONS/SIGNIFICANCE: MRSA nasal colonization is a significant
      risk factor for future MRSA infection; more so if detected by culture than PCR.
      Colonization with PVL-positive MRSA is associated with greater risk than PVL
      negative MRSA.

PMID- 24278162
TI  - Discovering subgroups of patients from DNA copy number data using NMF on
      compacted matrices.
AB  - In the study of complex genetic diseases, the identification of subgroups of
      patients sharing similar genetic characteristics represents a challenging task,
      for example, to improve treatment decision. One type of genetic lesion,
      frequently investigated in such disorders, is the change of the DNA copy number
      (CN) at specific genomic traits. Non-negative Matrix Factorization (NMF) is a
      standard technique to reduce the dimensionality of a data set and to cluster data
      samples, while keeping its most relevant information in meaningful components.
      Thus, it can be used to discover subgroups of patients from CN profiles. It is
      however computationally impractical for very high dimensional data, such as CN
      microarray data. Deciding the most suitable number of subgroups is also a
      challenging problem. The aim of this work is to derive a procedure to compact
      high dimensional data, in order to improve NMF applicability without compromising
      the quality of the clustering. This is particularly important for analyzing high
      resolution microarray data. Many commonly used quality measures, as well as our
      own measures, are employed to decide the number of subgroups and to assess the
      quality of the results. Our measures are based on the idea of identifying robust
      subgroups, inspired by biologically/clinically relevance instead of simply aiming
      at well-separated clusters. We evaluate our procedure using four real independent
      data sets. In these data sets, our method was able to find accurate subgroups
      with individual molecular and clinical features and outperformed the standard NMF
      in terms of accuracy in the factorization fitness function. Hence, it can be
      useful for the discovery of subgroups of patients with similar CN profiles in the
      study of heterogeneous diseases. 

PMID- 24278159
TI  - Genomic survey of pathogenicity determinants and VNTR markers in the cassava
      bacterial pathogen Xanthomonas axonopodis pv. Manihotis strain CIO151.
AB  - Xanthomonas axonopodis pv. manihotis (Xam) is the causal agent of bacterial
      blight of cassava, which is among the main components of human diet in Africa and
      South America. Current information about the molecular pathogenicity factors
      involved in the infection process of this organism is limited. Previous studies
      in other bacteria in this genus suggest that advanced draft genome sequences are
      valuable resources for molecular studies on their interaction with plants and
      could provide valuable tools for diagnostics and detection. Here we have
      generated the first manually annotated high-quality draft genome sequence of Xam
      strain CIO151. Its genomic structure is similar to that of other xanthomonads,
      especially Xanthomonas euvesicatoria and Xanthomonas citri pv. citri species.
      Several putative pathogenicity factors were identified, including type III
      effectors, cell wall-degrading enzymes and clusters encoding protein secretion
      systems. Specific characteristics in this genome include changes in the
      xanthomonadin cluster that could explain the lack of typical yellow color in all
      strains of this pathovar and the presence of 50 regions in the genome with
      atypical nucleotide composition. The genome sequence was used to predict and
      evaluate 22 variable number of tandem repeat (VNTR) loci that were subsequently
      demonstrated as polymorphic in representative Xam strains. Our results
      demonstrate that Xanthomonas axonopodis pv. manihotis strain CIO151 possesses ten
      clusters of pathogenicity factors conserved within the genus Xanthomonas. We
      report 126 genes that are potentially unique to Xam, as well as potential
      horizontal transfer events in the history of the genome. The relation of these
      regions with virulence and pathogenicity could explain several aspects of the
      biology of this pathogen, including its ability to colonize both vascular and non
      vascular tissues of cassava plants. A set of 16 robust, polymorphic VNTR loci
      will be useful to develop a multi-locus VNTR analysis scheme for epidemiological
      surveillance of this disease. 

PMID- 24278163
TI  - The detection of orientation continuity and discontinuity by cat V1 neurons.
AB  - The orientation tuning properties of the non-classical receptive field (nCRF or
      "surround") relative to that of the classical receptive field (CRF or "center")
      were tested for 119 neurons in the cat primary visual cortex (V1). The stimuli
      were concentric sinusoidal gratings generated on a computer screen with the
      center grating presented at an optimal orientation to stimulate the CRF and the
      surround grating with variable orientations stimulating the nCRF. Based on the
      presence or absence of surround suppression, measured by the suppression index at
      the optimal orientation of the cells, we subdivided the neurons into two
      categories: surround-suppressive (SS) cells and surround-non-suppressive (SN)
      cells. When stimulated with an optimally oriented grating centered at CRF, the SS
      cells showed increasing surround suppression when the stimulus grating was
      expanded beyond the boundary of the CRF, whereas for the SN cells, expanding the
      stimulus grating beyond the CRF caused no suppression of the center response. For
      the SS cells, strength of surround suppression was dependent on the relative
      orientation between CRF and nCRF: an iso-orientation grating over center and
      surround at the optimal orientation evoked strongest suppression and a surround
      grating orthogonal to the optimal center grating evoked the weakest or no
      suppression. By contrast, the SN cells showed slightly increased responses to an
      iso-orientation stimulus and weak suppression to orthogonal surround gratings.
      This iso-/orthogonal orientation selectivity between center and surround was
      analyzed in 22 SN and 97 SS cells, and for the two types of cells, the different
      center-surround orientation selectivity was dependent on the suppressive strength
      of the cells. We conclude that SN cells are suitable to detect orientation
      continuity or similarity between CRF and nCRF, whereas the SS cells are adapted
      to the detection of discontinuity or differences in orientation between CRF and
      nCRF. 

PMID- 24278164
TI  - Oxygen and ventilatory output during several activities of daily living performed
      by COPD patients stratified according to disease severity.
AB  - OBJECTIVES: To measure the oxygen and ventilatory output across all COPD stages
      performing 18 common ADL and identify the activities that present the highest
      metabolic and ventilatory output as well as to compare the energy expenditure
      within each disease severity. MATERIALS AND METHODS: Metabolic (VO2 and VCO2),
      ventilatory (f and VE), cardiovascular (HR) and dyspnea (Borg score) variables
      were assessed in one hundred COPD patients during the completion of eighteen ADL
      grouped into four activities domains: rest, personal care, labor activities and
      efforts. RESULTS: The activities with the highest proportional metabolic and
      ventilatory output (VO2/VO2max and VE/MVV) were walking with 2.5 Kg in each hand
      and walking with 5.0 Kg in one hand. Very severe patients presented the highest
      metabolic, ventilatory output and dyspnea than mild patients (p<0.05).
      CONCLUSIONS: COPD patients present an increased proportion of energy expenditure
      while performing activities of daily living. The activities that developed the
      highest metabolic and ventilatory output are the ones associated to upper and
      lower limbs movements combined. Very severe patients present the highest
      proportional estimated metabolic and ventilatory output and dyspnea. Activities
      of daily living are mainly limited by COPD's reduced ventilatory reserve.

PMID- 24278165
TI  - DCGL v2.0: an R package for unveiling differential regulation from differential
      co-expression.
AB  - MOTIVATION: Differential co-expression analysis (DCEA) has emerged in recent
      years as a novel, systematic investigation into gene expression data. While most
      DCEA studies or tools focus on the co-expression relationships among genes, some
      are developing a potentially more promising research domain, differential
      regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we
      provided functions to facilitate basic differential co-expression analyses;
      however, the output from DCGL v1.0 could not be translated into differential
      regulation mechanisms in a straightforward manner. RESULTS: To advance from DCEA
      to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named
      "Differential Regulation Analysis" (DRA) was designed, which consists of three
      major functions: DRsort, DRplot, and DRrank. DRsort selects differentially
      regulated genes (DRGs) and differentially regulated links (DRLs) according to the
      transcription factor (TF)-to-target information. DRrank prioritizes the TFs in
      terms of their potential relevance to the phenotype of interest. DRplot
      graphically visualizes differentially co-expressed links (DCLs) and/or TF-to
      target links in a network context. In addition to these new modules, we
      streamlined the codes from v1.0. The evaluation results proved that our
      differential regulation analysis is able to capture the regulators relevant to
      the biological subject. CONCLUSIONS: With ample functions to facilitate
      differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a
      DRA tool, which may unveil the underlying differential regulation from the
      observed differential co-expression. DCGL v2.0 can be applied to a wide range of
      gene expression data in order to systematically identify novel regulators that
      have not yet been documented as critical. AVAILABILITY: DCGL v2.0 package is
      available at http://cran.r-project.org/web/packages/DCGL/index.html or at our
      project home page http://lifecenter.sgst.cn/main/en/dcgl.jsp.

PMID- 24278166
TI  - Glucosylsphingosine is a highly sensitive and specific biomarker for primary
      diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian
      cohort of Gaucher disease patients.
AB  - BACKGROUND: Gaucher disease (GD) is the most common lysosomal storage disorder
      (LSD). Based on a deficient beta-glucocerebrosidase it leads to an accumulation
      of glucosylceramide. Standard diagnostic procedures include measurement of enzyme
      activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC
      as biomarkers. Even though chitotriosidase is the most well-established biomarker
      in GD, it is not specific for GD. Furthermore, it may be false negative in a
      significant percentage of GD patients due to mutation. Additionally,
      chitotriosidase reflects the changes in the course of the disease belatedly. This
      further enhances the need for a reliable biomarker, especially for the monitoring
      of the disease and the impact of potential treatments. METHODOLOGY: Here, we
      evaluated the sensitivity and specificity of the previously reported biomarker
      Glucosylsphingosine with regard to different control groups (healthy control vs.
      GD carriers vs. other LSDs). FINDINGS: Only GD patients displayed elevated levels
      of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls
      groups revealed concentrations below the pathological cut-off, verifying the
      specificity of Glucosylsphingosine as a biomarker for GD. In addition, we
      evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19
      patients, demonstrating a decrease in Glucosylsphingosine over time with the most
      pronounced reduction within the first 6 months of ERT. Furthermore, our data
      reveals a correlation between the medical consequence of specific mutations and
      Glucosylsphingosine. INTERPRETATION: In summary, Glucosylsphingosine is a very
      promising, reliable and specific biomarker for GD.

PMID- 24278167
TI  - The pathogen- and incidence-based DALY approach: an appropriate [corrected]
      methodology for estimating the burden of infectious diseases.
AB  - In 2009, the European Centre for Disease Prevention and Control initiated the
      'Burden of Communicable Diseases in Europe (BCoDE)' project to generate evidence
      based and comparable burden-of-disease estimates of infectious diseases in
      Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year
      (DALY), composed of years of life lost due to premature death (YLL) and due to
      disability (YLD). To better represent infectious diseases, a pathogen-based
      approach was used linking incident cases to sequelae through outcome trees.
      Health outcomes were included if an evidence-based causal relationship between
      infection and outcome was established. Life expectancy and disability weights
      were taken from the Global Burden of Disease Study and alternative studies.
      Disease progression parameters were based on literature. Country-specific
      incidence was based on surveillance data corrected for underestimation. Non
      typhoidal Salmonella spp. and Campylobacter spp. were used for illustration.
      Using the incidence- and pathogen-based DALY approach the total burden for
      Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780
      DALYs per year in the Netherlands (average of 2005-2007). Sequelae accounted for
      56% and 82% of the total burden of Salmonella spp. and Campylobacter spp.,
      respectively. The incidence- and pathogen-based DALY methodology allows in the
      case of infectious diseases a more comprehensive calculation of the disease
      burden as subsequent sequelae are fully taken into account. Not considering
      subsequent sequelae would strongly underestimate the burden of infectious
      diseases. Estimates can be used to support prioritisation and comparison of
      infectious diseases and other health conditions, both within a country and
      between countries. 

PMID- 24278168
TI  - Presep: predicting the propensity of a protein being secreted into the
      supernatant when expressed in Pichia pastoris.
AB  - Pichia pastoris is commonly used for the production of recombinant proteins due
      to its preferential secretion of recombinant proteins, resulting in lower
      production costs and increased yields of target proteins. However, not all
      recombinant proteins can be successfully secreted in P. pastoris. A computational
      method that predicts the likelihood of a protein being secreted into the
      supernatant would be of considerable value; however, to the best of our
      knowledge, no such tool has yet been developed. We present a machine-learning
      approach called Presep to assess the likelihood of a recombinant protein being
      secreted by P. pastoris based on its pseudo amino acid composition (PseAA). Using
      a 20-fold cross validation, Presep demonstrated a high degree of accuracy, with
      Matthews correlation coefficient (MCC) and overall accuracy (Q2) scores of 0.78
      and 95%, respectively. Computational results were validated experimentally, with
      six beta-galactosidase genes expressed in P. pastoris strain GS115 to verify
      Presep model predictions. A strong correlation (R(2) = 0.967) was observed
      between Presep prediction secretion propensity and the experimental secretion
      percentage. Together, these results demonstrate the ability of the Presep model
      for predicting the secretion propensity of P. pastoris for a given protein. This
      model may serve as a valuable tool for determining the utility of P. pastoris as
      a host organism prior to initiating biological experiments. The Presep prediction
      tool can be freely downloaded at http://www.mobioinfor.cn/Presep. 

PMID- 24278169
TI  - The severity of experimental autoimmune cystitis can be ameliorated by anti
      CXCL10 Ab treatment.
AB  - BACKGROUND: Interstitial cystitis (IC), more recently called painful bladder
      syndrome (PBS) is a complex disease associated with chronic bladder inflammation
      that primarily affects women. Its symptoms include frequent urinary urgency
      accompanied by discomfort or pain in the bladder and lower abdomen. In the United
      States, eight million people, mostly women, have IC/PBS. New evidence that
      autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered
      interest. METHODOLOGY/PRINCIPAL FINDINGS: SWXJ mice immunized with a homogenate
      of similar mice's urinary bladders develop an autoimmune phenotype comparable to
      clinical IC with functional and histological alterations confined to the urinary
      bladder. Using the murine model of experimental autoimmune cystitis (EAC), we
      found that serum levels of CXCR3 ligand and local T helper type 1 (Th1) cytokine
      are elevated. Also, IFN-gamma-inducible protein10 (CXCL10) blockade attenuated
      overall cystitis severity scores; reversed the development of IC; decreased local
      production of CXCR3 and its ligands, IFN-gamma, and tumor necrosis factor-alpha
      (TNF-alpha); and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4(+)
      T cells, mast cells, and neutrophils infiltrates were reduced following anti
      CXCL10 antibody (Ab) treatment of mice. Anti-CXCL10 Ab treatment also reversed
      the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The
      decreased number and percentage of systemic CD4(+) T cells in EAC mice returned
      to normal after anti-CXCL10 Ab treatment. CONCLUSION/SIGNIFICANCE: Taken
      together, our findings provide important new information about the mechanisms
      underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS.
      CXCL10 has the potential for use in developing new therapy for IC/PBS.

PMID- 24278170
TI  - Risk factors for mercury exposure of children in a rural mining town in northern
      Chile.
AB  - OBJECTIVE: Traditional gold mining is associated with mercury exposure.
      Especially vulnerable to its neurotoxic effects is the developing nervous system
      of a child. We aimed to investigate risk factors of mercury exposure among
      children in a rural mining town in Chile. METHODS: Using a validated
      questionnaire distributed to the parents of the children, a priori mercury risk
      factors, potential exposure pathways and demographics of the children were
      obtained. Mercury levels were measured through analyzing fingernail samples.
      Logistic regression modeling the effect of risk factors on mercury levels above
      the 75(th) percentile were made, adjusted for potential confounders. RESULTS: The
      288 children had a mean age of 9.6 years (SD = 1.9). The mean mercury level in
      the study population was 0.13 ug/g (SD 0.11, median 0.10, range 0.001-0.86 ug/g).
      The strongest risk factor for children's odds of high mercury levels (>75(th)
      percentile, 0.165 ug/g) was to play inside a house where a family member worked
      with mercury (OR adjusted 3.49 95% CI 1.23-9.89). Additionally, children whose
      parents worked in industrial gold mining had higher odds of high mercury levels
      than children whose parents worked in industrial copper mining or outside mining
      activities. CONCLUSION: Mercury exposure through small-scale gold mining might
      affect children in their home environments. These results may further help to
      convince the local population of banning mercury burning inside the households.

PMID- 24278171
TI  - PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through
      inhibiting NF-kappaB-mediated inflammatory response.
AB  - Acute lung injury (ALI) is characterized by overwhelming lung inflammation and
      anti-inflammation treatment is proposed to be a therapeutic strategy for ALI.
      Poly (ADP-ribose) polymerase-1 has been demonstrated to be involved in tissue
      inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinyl)butoxy]
      1(2H)-isoquinoline (DPQ), exerts anti-inflammatory effect. However, it is still
      unclear whether the DPQ possesses the protective effect on ALI and what
      mechanisms are involved. In this study, we tested the effect of DPQ on the lung
      inflammation induced by lipopolysaccharide (LPS) challenge in mice. We found that
      6 h-LPS challenge induced significant lung inflammation and vascular leakage in
      mice. Treatment with DPQ at the dose of 10 MUg/kg markedly reduced the neutrophil
      infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory
      mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ
      treatment, accompanied by the inhibition of apoptotic cell death in mice lungs.
      In addition, we isolated mice peritoneal macrophages and showed pretreatment with
      DPQ at 10 MUM inhibited the production of cytokines in the macrophages following
      LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation
      of IkappaB-alpha, subsequently blocked the activation of nuclear factor (NF)
      kappaB induced by LPS in vivo and in vitro. Taken together, our results show that
      DPQ treatment inhibits NF-kappaB signaling in macrophages and protects mice
      against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose) polymerase
      1 may be a potential and effective approach to resolve inflammation for the
      treatment of ALI. 

PMID- 24278172
TI  - TLQP-21 protects human umbilical vein endothelial cells against high-glucose
      induced apoptosis by increasing G6PD expression.
AB  - Hyperglycemia causes oxidative stress that could damage vascular endothelial
      cells, leading to cardiovascular complications. The Vgf gene was identified as a
      nerve growth factor-responsive gene, and its protein product, VGF, is
      characterized by the presence of partially cleaved products. One of the VGF
      derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556
      576). Past studies have reported that TLQP-21 could stimulate insulin secretion
      in pancreatic cells and protect these cells from apoptosis, which suggests that
      TLQP-21 has a potential function in diabetes therapy. Here, we explore the
      protective role of TLQP-21 against the high glucose-mediated injury of vascular
      endothelial cells. Using human umbilical vascular endothelial cells (HUVECs), we
      demonstrated that TLQP-21 (10 or 50 nM) dose-dependently prevented apoptosis
      under high-glucose (30 mmol/L) conditions (the normal glucose concentration is
      5.6 mmol/L). TLQP-21 enhanced the expression of NAPDH, resulting in upregulation
      of glutathione (GSH) and a reduction in the levels of reactive oxygen species
      (ROS). TLQP-21 also upregulated the expression of glucose-6-phosphate
      dehydrogenase (G6PD), which is known as the main source of NADPH. Knockdown of
      G6PD almost completely blocked the increase of NADPH induced by TLQP-21,
      indicating that TLQP-21 functions mainly through G6PD to promote NADPH
      generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn
      may increase the synthesis of NADPH and GSH, thereby partially restoring the
      redox status of vascular endothelial cells under high glucose injury. We propose
      that TLQP-21 is a promising drug for diabetes therapy. 

PMID- 24278173
TI  - Biocompatibility of a novel cyanoacrylate based tissue adhesive: cytotoxicity and
      biochemical property evaluation.
AB  - Cyanoacrylate (CA) is most widely used as a medical and commercial tissue
      adhesive because of easier wound closure, good cosmetic results and little
      discomfort. But, CA-based tissue adhesives have some limitations including the
      release of cytotoxic chemicals during biodegradation. In previous study, we made
      prepolymerized allyl 2-CA (PACA) based tissue adhesive, resulting in longer chain
      structure. In this study, we investigated a biocompatibility of PACA as
      alternative tissue adhesive for medical application, comparing with that of
      Dermabond(r) as commercial tissue adhesive. The biocompatibility of PACA was
      evaluated for short-term (24 hr) and long-term (3 and 7 days) using conventional
      cytotoxicity (WST, neutral red, LIVE/DEAD and TUNEL) assays, hematoxylin-eosin
      (H&E) and Masson trichrome (MT) staining. Besides we examined the biochemical
      changes in cells and DNA induced by PACA and Dermabond(r) utilizing Raman
      spectroscopy which could observe the denaturation and conformational changes in
      protein, as well as disintegration of the DNA/RNA by cell death. In particular,
      we analyzed Raman spectrum using the multivariate statistical methods including
      principal component analysis (PCA) and support vector machine (SVM). As a result,
      PACA and Dermabond(r) tissue adhesive treated cells and tissues showed no
      difference of the cell viability values, histological analysis and Raman spectral
      intensity. Also, the classification analysis by means of PCA-SVM classifier could
      not discriminate the difference between the PACA and Dermabond(r) treated cells
      and DNA. Therefore we suggest that novel PACA might be useful as potential tissue
      adhesive with effective biocompatibility. 

PMID- 24278174
TI  - A celiac cellular phenotype, with altered LPP sub-cellular distribution, is
      inducible in controls by the toxic gliadin peptide P31-43.
AB  - Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic
      background, caused by gliadin-containing food. Undigested gliadin peptides P31-43
      and P57-68 induce innate and adaptive T cell-mediated immune responses,
      respectively. Alterations in the cell shape and actin cytoskeleton are present in
      celiac enterocytes, and gliadin peptides induce actin rearrangements in both the
      CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and
      focal adhesions, sites of membrane attachment to the extracellular matrix. The
      locus of the human Lipoma Preferred Partner (LPP) gene was identified as strongly
      associated with CD using genome-wide association studies (GWAS). The LPP protein
      plays an important role in focal adhesion architecture and acts as a
      transcription factor in the nucleus. In this study, we examined the hypothesis
      that a constitutive alteration of the cell shape and the cytoskeleton, involving
      LPP, occurs in a cell compartment far from the main inflammation site in CD
      fibroblasts from skin explants. We analyzed the cell shape, actin organization,
      focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and
      adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free
      Diet (GFD) and controls, without and with treatment with A-gliadin peptide P31
      43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by
      an altered cell shape and actin organization, increased number of focal
      adhesions, and altered intracellular LPP protein distribution. The treatment of
      controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype
      regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub
      cellular distribution, suggesting a close association between these alterations
      and CD pathogenesis. 

PMID- 24278175
TI  - Bi-factor analysis based on noise-reduction (BIFANR): a new algorithm for
      detecting coevolving amino acid sites in proteins.
AB  - Previous statistical analyses have shown that amino acid sites in a protein
      evolve in a correlated way instead of independently. Even though located
      distantly in the linear sequence, the coevolved amino acids could be spatially
      adjacent in the tertiary structure, and constitute specific protein sectors.
      Moreover, these protein sectors are independent of one another in structure,
      function, and even evolution. Thus, systematic studies on protein sectors inside
      a protein will contribute to the clarification of protein function. In this
      paper, we propose a new algorithm BIFANR (Bi-factor Analysis Based on Noise
      reduction) for detecting protein sectors in amino acid sequences. After applying
      BIFANR on S1A family and PDZ family, we carried out internal correlation test,
      statistical independence test, evolutionary rate analysis, evolutionary
      independence analysis, and function analysis to assess the prediction. The
      results showed that the amino acids in certain predicted protein sector are
      closely correlated in structure, function, and evolution, while protein sectors
      are nearly statistically independent. The results also indicated that the protein
      sectors have distinct evolutionary directions. In addition, compared with other
      algorithms, BIFANR has higher accuracy and robustness under the influence of
      noise sites. 

PMID- 24278176
TI  - Daily online testing in large classes: boosting college performance while
      reducing achievement gaps.
AB  - An in-class computer-based system, that included daily online testing, was
      introduced to two large university classes. We examined subsequent improvements
      in academic performance and reductions in the achievement gaps between lower- and
      upper-middle class students in academic performance. Students (N = 901) brought
      laptop computers to classes and took daily quizzes that provided immediate and
      personalized feedback. Student performance was compared with the same data for
      traditional classes taught previously by the same instructors (N = 935). Exam
      performance was approximately half a letter grade above previous semesters, based
      on comparisons of identical questions asked from earlier years. Students in the
      experimental classes performed better in other classes, both in the semester they
      took the course and in subsequent semester classes. The new system resulted in a
      50% reduction in the achievement gap as measured by grades among students of
      different social classes. These findings suggest that frequent consequential
      quizzing should be used routinely in large lecture courses to improve performance
      in class and in other concurrent and subsequent courses. 

PMID- 24278178
TI  - Comparative morphology of premolar foramen in lagomorphs (Mammalia: Glires) and
      its functional and phylogenetic implications.
AB  - Lagomorphs (a group that consists of pikas, hares, rabbits and allies) are
      notable for their conservative morphology retained for most of their over 50
      million years evolutionary history. On the other hand, their remarkable
      morphological uniformity partly stems from a considerable number of homoplasies
      in cranial and dental structures that hamper phylogenetic analyses. The premolar
      foramen, an opening in the palate of lagomorphs, has been characterized as an
      important synapomorphy of one clade, Ochotonidae (pikas). Within Lagomorpha,
      however, its phylogenetic distribution is much wider, the foramen being present
      not only in all ochotonids but also in leporids and stem taxa; its morphology and
      incidence also varies considerably across the order, even intraspecifically. In
      this study, we provide a broad survey of the taxonomic distribution of the
      premolar foramen in extant and fossil Lagomorpha and describe in detail the
      morphological variation of this character within the group. Micro-computed
      tomography was used to examine the hard palate and infraorbital groove morphology
      in Poelagus (Leporidae) and Ochotona. Scans revealed the course and contacts of
      the canal behind the premolar foramen and structural differences between the two
      crown clades. We propose that the premolar foramen has evolved independently in
      several lineages of Lagomorpha, and we discuss development and function of this
      foramen in the lagomorph skull. This study shows the importance of comprehensive
      studies on phylogenetically informative non-dental characters in Lagomorpha. 

PMID- 24278177
TI  - Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody
      against subgenotypes B1, B4, B5 and C4A in adult volunteers.
AB  - BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and
      mouth diseases (HFMD) in Asia. No effective EV71 vaccine is available. A
      randomized and open-label phase I clinical study registered with
      ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and
      immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac) at 5-
      and 10-ug doses. In this study we report the cross-neutralizing antibody
      responses from each volunteer against different subgenotypes of EV71 and CVA16.
      METHODS: Sixty eligible healthy adults were recruited and vaccinated. Blood
      samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A,
      C4B and CVA16 for cross-neutralizing antibody responses. RESULTS: The
      immunogenicity of both 5- and 10- ug doses were found to be very similar.
      Approximately 45% of the participants had <8 pre-vaccination neutralization
      titers (Nt) against the B4 vaccine strain. After the first EV71vac immunization,
      95% of vaccinees have >4-fold increase in Nt, but there was no further increase
      in Nt after the second dose. EV71vac induced very strong cross-neutralizing
      antibody responses in >85% of volunteers without pre-existing Nt against
      subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody
      responses (~20% of participants) against a C4B and Coxsackie virus A16. Over 90%
      of vaccinated volunteers did not develop cross-neutralizing antibody responses
      (Nt<8) against a C2 strain. EV71vac can boost and significantly enhance the
      neutralizing antibody responses in volunteers who already had pre-vaccination
      antibodies against EV71 and/or CVA16. CONCLUSION: EV71vac is efficient in
      eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4,
      B5, and C4A, and provides the rationale for its evaluation in phase II clinical
      trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01268787.

PMID- 24278179
TI  - Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC
      populations on lung primary tumors and metastasis.
AB  - Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and
      recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific
      compounds may be an effective approach to reduce lung cancer growth and
      metastasis. The aim of this study was to investigate the effect of salinomycin, a
      selective inhibitor of CSCs, with or without combination with paclitaxel, in a
      metastatic model. To evaluate the effect of these drugs in metastasis and tumor
      microenvironment we took advantage of the immunocompetent and highly metastatic
      LLC mouse model. Aldefluor assays were used to analyze the ALDH+/- populations in
      murine LLC and human H460 and H1299 lung cancer cells. Salinomycin reduced the
      proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such
      population. The same effect was observed for the H460 and H1299 cell lines.
      Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7
      fold, but paclitaxel showed no effect. In in vivo experiments, paclitaxel reduced
      primary tumor volume but increased the number of metastatic nodules (p<0.05),
      whereas salinomycin had no effect on primary tumors but reduced lung metastasis
      (p<0.05). Combination of both drugs did not improve the effect of single
      therapies. ALDH1A1, SOX2, CXCR4 and SDF-1 mRNA levels were higher in metastatic
      lesions than in primary tumors, and were significantly elevated in both locations
      by paclitaxel treatment. On the contrary, such levels were reduced (or in some
      cases did not change) when mice were administered with salinomycin. The number of
      F4/80+ and CD11b+ cells was also reduced upon administration of both drugs, but
      particularly in metastasis. These results show that salinomycin targets ALDH+
      lung CSCs, which has important therapeutic effects in vivo by reducing metastatic
      lesions. In contrast, paclitaxel (although reducing primary tumor growth)
      promotes the selection of ALDH+ cells that likely modify the lung
      microenvironment to foster metastasis. 

PMID- 24278180
TI  - Molecular engineering of fungal GH5 and GH26 beta-(1,4)-mannanases toward
      improvement of enzyme activity.
AB  - Microbial mannanases are biotechnologically important enzymes since they target
      the hydrolysis of hemicellulosic polysaccharides of softwood biomass into simple
      molecules like manno-oligosaccharides and mannose. In this study, we have
      implemented a strategy of molecular engineering in the yeast Yarrowia lipolytica
      to improve the specific activity of two fungal endo-mannanases, PaMan5A and
      PaMan26A, which belong to the glycoside hydrolase (GH) families GH5 and GH26,
      respectively. Following random mutagenesis and two steps of high-throughput
      enzymatic screening, we identified several PaMan5A and PaMan26A mutants that
      displayed improved kinetic constants for the hydrolysis of galactomannan.
      Examination of the three-dimensional structures of PaMan5A and PaMan26A revealed
      which of the mutated residues are potentially important for enzyme function.
      Among them, the PaMan5A-G311S single mutant, which displayed an impressive 8.2
      fold increase in kcat /KM due to a significant decrease of KM, is located within
      the core of the enzyme. The PaMan5A-K139R/Y223H double mutant revealed
      modification of hydrolysis products probably in relation to an amino-acid
      substitution located nearby one of the positive subsites. The PaMan26A
      P140L/D416G double mutant yielded a 30% increase in kcat /KM compared to the
      parental enzyme. It displayed a mutation in the linker region (P140L) that may
      confer more flexibility to the linker and another mutation (D416G) located at the
      entrance of the catalytic cleft that may promote the entrance of the substrate
      into the active site. Taken together, these results show that the directed
      evolution strategy implemented in this study was very pertinent since a
      straightforward round of random mutagenesis yielded significantly improved
      variants, in terms of catalytic efiiciency (kcat/KM). 

PMID- 24278181
TI  - Comparing bacterial community composition between healthy and white plague-like
      disease states in Orbicella annularis using PhyloChipTM G3 microarrays.
AB  - Coral disease is a global problem. Diseases are typically named or described
      based on macroscopic changes, but broad signs of coral distress such as tissue
      loss or discoloration are unlikely to be specific to a particular pathogen. For
      example, there appear to be multiple diseases that manifest the rapid tissue loss
      that characterizes 'white plague.' PhyloChipTM G3 microarrays were used to
      compare the bacterial community composition of both healthy and white plague-like
      diseased corals. Samples of lobed star coral (Orbicella annularis, formerly of
      the genus Montastraea[1]) were collected from two geographically distinct areas,
      Dry Tortugas National Park and Virgin Islands National Park, to determine if
      there were biogeographic differences between the diseases. In fact, all diseased
      samples clustered together, however there was no consistent link to Aurantimonas
      coralicida, which has been described as the causative agent of white plague type
      II. The microarrays revealed a large amount of bacterial heterogeneity within the
      healthy corals and less diversity in the diseased corals. Gram-positive bacterial
      groups (Actinobacteria, Firmicutes) comprised a greater proportion of the
      operational taxonomic units (OTUs) unique to healthy samples. Diseased samples
      were enriched in OTUs from the families Corynebacteriaceae, Lachnospiraceae,
      Rhodobacteraceae, and Streptococcaceae. Much previous coral disease work has used
      clone libraries, which seem to be methodologically biased toward recovery of Gram
      negative bacterial sequences and may therefore have missed the importance of Gram
      positive groups. The PhyloChipTMdata presented here provide a broader
      characterization of the bacterial community changes that occur within Orbicella
      annularis during the shift from a healthy to diseased state. 

PMID- 24278182
TI  - MicroRNA and mRNA signatures in ischemia reperfusion injury in heart
      transplantation.
AB  - Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart
      transplantation, leading to graft failures and lower long-term survival rate of
      the recipient. Several studies have demonstrated that microRNAs (miRNAs) are
      vital regulators of signalling pathways involved in I/R injury. The present study
      aims to quantify the altered expression levels of miRNA and mRNA upon I/R injury
      in a mouse heart transplantation model, and to investigate whether these miRNA
      can regulate genes involved in I/R injury. We performed heterotopic heart
      transplantation on mouse models to generate heart tissue samples with I/R and non
      I/R (control). The expression levels of miRNAs as well as genes were measured in
      heart grafts by microarray and real time RT-PCR. miRNA alteration in
      cardiomyocytes exposed to hypoxia was also detected by qRT-PCR. We observed
      significant alterations in miRNA and gene expression profile after I/R injury.
      There were 39 miRNAs significantly downregulated and 20 upregulated up to 1.5
      fold in heart grafts with I/R injury compared with the grafts without I/R. 48
      genes were observed with 3 fold change and p<0.05 and 18 signalling pathways were
      enriched using Keggs pathway library. Additionally, hypoxia/reperfusion induced
      primary cardiomyocyte apoptosis and altered miRNA expression profiles. In
      conclusion, this is the first report on miRNA expression profile for heart
      transplantation associated with I/R injury. These findings provide us with an
      insight into the role of miRNA in I/R injury in heart transplantation. 

PMID- 24278183
TI  - Depression as a risk factor for mortality in individuals with diabetes: a meta
      analysis of prospective studies.
AB  - OBJECTIVE: To quantify the impact of depression measured by self-reports and
      depression measured by clinical interview on all-cause mortality in individuals
      with diabetes and to analyze the strength of both associations, the influence of
      covariates, and possible differences between studies assessing self-rated
      depressive symptoms and those using a clinical interview to measure depression as
      predictors of mortality. RESEARCH DESIGN AND METHODS: PUBMED and PsycINFO were
      searched up to July 2013 for prospective studies assessing depression, diabetes
      and mortality. The pooled hazard ratios were calculated using random-effects
      models. RESULTS: Sixteen studies met the inclusion criteria. After adjustment for
      demographic variables depression measured by self-reports was associated with an
      increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89-3.47), and the
      mortality risk remained high after additional adjustment for diabetes
      complications (HR = 1.76, 95% CI 1.45-2.14,). Six studies reporting adjusted HRs
      for depression measured by clinical interviews supported the results of the other
      models (HR = 1.49, 95% CI 1.15-1.93). CONCLUSIONS: Both depression measured by
      self-report and depression measured by clinical interview have an unfavorable
      impact on mortality in individuals with diabetes. The results, however, are
      limited by the heterogeneity of the primary studies. It remains unclear whether
      self-reports or clinical interviews for depression are the more precise
      predictor.

PMID- 24278184
TI  - The USP21 short variant (USP21SV) lacking NES, located mostly in the nucleus in
      vivo, activates transcription by deubiquitylating ubH2A in vitro.
AB  - USP21 is a deubiquitylase that catalyzes isopeptide bond hydrolysis between
      ubiquitin and histone H2A. Since ubiqutylated H2A (ubH2A) represses
      transcription, USP21 plays a role in transcriptional activation. On the other
      hand, the localization of USP21 suggests it has an additional function in the
      cytoplasm. Here, we identified a USP21 short variant (USP21SV) lacking a nuclear
      export signal (NES). Differential localization of USP21SV, more in the nucleus
      than the USP21 long variant (USP21LV), suggests they have redundant roles in the
      cell. Ectopic expression of both USP21 variants decreased ubH2A in the nucleus.
      Furthermore, both recombinant USP21 variants activate transcription by
      deubiquitylating ubH2A in vitro. These data suggest multiple roles for USP21 in
      the ubiquitylation-deubiquitylation network in the cell. 

PMID- 24278185
TI  - Dissecting the effects of simulated cattle activity on floristic composition and
      functional traits in Mediterranean grasslands.
AB  - Livestock exerts direct and indirect effects on plant communities, changing
      colonization and extinction rates of species and the surrounding environmental
      conditions. There is scarce knowledge on how and to what extent these effects
      control the floristic and functional composition of plant communities in
      grasslands. We performed an experiment that included several treatments
      simulating trampling, defoliation, faeces addition and their combinations in a
      Mediterranean scrub community grazing-abandoned for at least 50 years. We
      monitored the plots for four years, and collected data on species composition,
      photosynthetically active radiation (PAR) and red?far-red ratio (R?FR), soil
      moisture and compaction. We estimated community weighted means (CWM) for height,
      habit, life cycle, seed mass and SLA. Neither compaction nor soil moisture were
      modified by the treatments, while PAR and R?FR increased in all treatments in
      comparison to the Control and Faeces treatments. The floristic composition of all
      treatments, except for Faeces, converged over time, but deviated from that of the
      Control. The functional traits displayed the trends expected in the presence of
      grazing: loss of erect species and increased cover of short species with light
      seeds, with rosettes and prostrate habit. However, contrary to the results in
      literature, SLA was lower in all the treatments than Control plots. Like the
      results for floristic composition, all treatments except for Faeces converged
      towards a similar functional composition at the end of the four year period. The
      results of this study show the initial evolution of a Mediterranean plant
      community in the presence of grazing, driven primarily by the destructive action
      of livestock. These actions seem to directly affect the rates of
      extinction/colonization, and indirectly affect the light environment but not the
      soil conditions. However, their effects on floristic and trait composition do not
      seem to differ, at least at the small spatio-temporal scale. 

PMID- 24278186
TI  - Anthocyanin-rich purple corn extract inhibit diabetes-associated glomerular
      angiogenesis.
AB  - Diabetic nephropathy (DN) is one of the major diabetic complications and the
      leading cause of end-stage renal disease. Abnormal angiogenesis results in new
      vessels that are often immature and play a pathological role in DN, contributing
      to renal fibrosis and disrupting glomerular failure. Purple corn has been
      utilized as a daily food and exerts disease-preventive activities. This study was
      designed to investigate whether anthocyanin-rich purple corn extract (PCE)
      prevented glomerular angiogenesis under hyperglycemic conditions. Human
      endothelial cells were cultured in conditioned media of mesangial cells exposed
      to 33 mM high glucose (HG-HRMC-CM). PCE decreased endothelial expression of
      vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF)
      1alpha induced by HG-HRMC-CM. Additionally, PCE attenuated the induction of the
      endothelial marker of platelet endothelial cell adhesion molecule (PECAM)-1 and
      integrin beta3 enhanced in HG-HRMC-CM. Endothelial tube formation promoted by HG
      HRMC-CM was disrupted in the presence of PCE. In the in vivo study employing
      db/db mice treated with 10 mg/kg PCE for 8 weeks, PCE alleviated glomerular
      angiogenesis of diabetic kidneys by attenuating the induction of VEGF and HIF
      1alpha. Oral administration of PCE retarded the endothelial proliferation in
      db/db mouse kidneys, evidenced by its inhibition of the induction of vascular
      endothelium-cadherin, PECAM-1 and Ki-67. PCE diminished the mesangial and
      endothelial induction of angiopoietin (Angpt) proteins under hypeglycemic
      conditions. The induction and activation of VEGF receptor 2 (VEGFR2) were
      dampened by treating PCE to db/db mice. These results demonstrate that PCE
      antagonized glomerular angiogenesis due to chronic hyperglycemia and diabetes
      through disturbing the Angpt-Tie-2 ligand-receptor system linked to renal VEGFR2
      signaling pathway. Therefore, PCE may be a potent therapeutic agent targeting
      abnormal angiogenesis in DN leading to kidney failure. 

PMID- 24278187
TI  - Impact of delay to cryopreservation on RNA integrity and genome-wide expression
      profiles in resected tumor samples.
AB  - The quality of tissue samples and extracted mRNA is a major source of variability
      in tumor transcriptome analysis using genome-wide expression microarrays. During
      and immediately after surgical tumor resection, tissues are exposed to metabolic,
      biochemical and physical stresses characterized as "warm ischemia". Current
      practice advocates cryopreservation of biosamples within 30 minutes of resection,
      but this recommendation has not been systematically validated by measurements of
      mRNA decay over time. Using Illumina HumanHT-12 v3 Expression BeadChips,
      providing a genome-wide coverage of over 24,000 genes, we have analyzed gene
      expression variation in samples of 3 hepatocellular carcinomas (HCC) and 3 lung
      carcinomas (LC) cryopreserved at times up to 2 hours after resection. RNA
      Integrity Numbers (RIN) revealed no significant deterioration of mRNA up to 2
      hours after resection. Genome-wide transcriptome analysis detected non
      significant gene expression variations of -3.5%/hr (95% CI: -7.0%/hr to 0.1%/hr;
      p = 0.054). In LC, no consistent gene expression pattern was detected in relation
      with warm ischemia. In HCC, a signature of 6 up-regulated genes (CYP2E1, IGLL1,
      CABYR, CLDN2, NQO1, SCL13A5) and 6 down-regulated genes (MT1G, MT1H, MT1E, MT1F,
      HABP2, SPINK1) was identified (FDR <0.05). Overall, our observations support
      current recommendation of time to cryopreservation of up to 30 minutes and
      emphasize the need for identifying tissue-specific genes deregulated following
      resection to avoid misinterpreting expression changes induced by warm ischemia as
      pathologically significant changes. 

PMID- 24278188
TI  - Psychometrics of the Short Form 36 Health Survey version 2 (SF-36v2) and the
      Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese mainland patients
      with methadone maintenance treatment.
AB  - OBJECTIVE: To test psychometrics of the Short Form 36 Health Survey version 2 (SF
      36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese
      mainland patients with methadone maintenance treatment (MMT). METHODS: A total of
      1,212 patients were recruited from two MMT clinics in Xi'an, China. Reliability
      was estimated with Cronbach's alpha and intra-class correlation (ICC). Convergent
      and discriminant validity was assessed using multitrait-multimethod correlation
      matrix. Sensitivity was measured with ANOVA and relative efficiency.
      Responsiveness was evaluated by pre-post paired-samples t-test and standardized
      response mean based on the patients' health status changes following 6-month
      period. RESULTS: Cronbach's alpha of the SF-36v2 physical and mental summary
      components were 0.80 and 0.86 (eight scales range 0.73-0.92) and the QOL-DAv2.0
      was 0.96 (four scales range: 0.80-0.93). ICC of the SF-36v2 two components were
      0.86 and 0.85 (eight scales range: 0.72-0.87) and the QOL-DAv2.0 was 0.94 (four
      scales range: 0.88-0.92). Convergent validity was lower between the two
      instruments (gamma <0.70) while discriminant validity was acceptable within each
      instrument. Sensitivity was satisfied in self-evaluated health status (both
      instruments) and average daily methadone dose (SF-36v2 physical functioning and
      vitality scales; QOL-DAv2.0 except psychology scale). Responsiveness was
      acceptable in the improved health status change (SF-36v2 except vitality scale;
      QOL-DAv2.0 except psychology and symptoms scales) and deteriorated health status
      change (SF-36v2 except vitality, social functioning and mental health scales; QOL
      DAv2.0 except society scale). CONCLUSIONS: The SF-36v2 and the QOL-DAv2.0 are
      valid tools and can be used independently or complementary according to different
      emphases of health-related quality of life evaluation in patients with MMT.

PMID- 24278189
TI  - Corticomuscular transmission of tremor signals by propriospinal neurons in
      Parkinson's disease.
AB  - Cortical oscillatory signals of single and double tremor frequencies act together
      to cause tremor in the peripheral limbs of patients with Parkinson's disease
      (PD). But the corticospinal pathway that transmits the tremor signals has not
      been clarified, and how alternating bursts of antagonistic muscle activations are
      generated from the cortical oscillatory signals is not well understood. This
      paper investigates the plausible role of propriospinal neurons (PN) in C3-C4 in
      transmitting the cortical oscillatory signals to peripheral muscles. Kinematics
      data and surface electromyogram (EMG) of tremor in forearm were collected from PD
      patients. A PN network model was constructed based on known neurophysiological
      connections of PN. The cortical efferent signal of double tremor frequencies were
      integrated at the PN network, whose outputs drove the muscles of a virtual arm
      (VA) model to simulate tremor behaviors. The cortical efferent signal of single
      tremor frequency actuated muscle spindles. By comparing tremor data of PD
      patients and the results of model simulation, we examined two hypotheses
      regarding the corticospinal transmission of oscillatory signals in Parkinsonian
      tremor. Hypothesis I stated that the oscillatory cortical signals were
      transmitted via the mono-synaptic corticospinal pathways bypassing the PN
      network. The alternative hypothesis II stated that they were transmitted by way
      of PN multi-synaptic corticospinal pathway. Simulations indicated that without
      the PN network, the alternating burst patterns of antagonistic muscle EMGs could
      not be reliably generated, rejecting the first hypothesis. However, with the PN
      network, the alternating burst patterns of antagonist EMGs were naturally
      reproduced under all conditions of cortical oscillations. The results suggest
      that cortical commands of single and double tremor frequencies are further
      processed at PN to compute the alternating burst patterns in flexor and extensor
      muscles, and the neuromuscular dynamics demonstrated a frequency dependent
      damping on tremor, which may prevent tremor above 8 Hz to occur. 

PMID- 24278190
TI  - Factors limiting performance in a multitone intensity-discrimination task:
      disentangling non-optimal decision weights and increased internal noise.
AB  - To identify factors limiting performance in multitone intensity discrimination,
      we presented sequences of five pure tones alternating in level between loud (85
      dB SPL) and soft (30, 55, or 80 dB SPL). In the "overall-intensity task",
      listeners detected a level increment on all of the five tones. In the "masking
      task", the level increment was imposed only on the soft tones, rendering the soft
      tones targets and loud tones task-irrelevant maskers. Decision weights
      quantifying the importance of the five tone levels for the decision were
      estimated using methods of molecular psychophysics. Compatible with previous
      studies, listeners placed higher weights on the loud tones than on the soft tones
      in the overall-intensity condition. In the masking task, the decisions were
      systematically influenced by the to-be-ignored loud tones (maskers). Using a
      maximum-likelihood technique, we estimated the internal noise variance and tested
      whether the internal noise was higher in the alternating-level five-tone
      sequences than in sequences presenting only the soft or only the loud tones. For
      the overall-intensity task, we found no evidence for increased internal noise,
      but listeners applied suboptimal decision weights. These results are compatible
      with the hypothesis that the presence of the loud tones does not impair the
      precision of the representation of the intensity of the soft tones available at
      the decision stage, but that this information is not used in an optimal fashion
      due to a difficulty in attending to the soft tones. For the masking task, in some
      cases our data indicated an increase in internal noise. Additionally, listeners
      applied suboptimal decision weights. The maximum-likelihood analyses we developed
      should also be useful for other tasks or other sensory modalities. 

PMID- 24278191
TI  - Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study.
AB  - Methylene blue (MB) has unique energy-enhancing and antioxidant properties and is
      FDA-approved drug to treat methemoglobinemia and cyanide poisoning. This study
      evaluated the efficacy of MB to treat ischemic stroke in rats using longitudinal
      MRI and behavioral measures. Rats were subjected to 60-minute middle-cerebral
      artery occlusion. In a randomized double-blinded design, vehicle or MB was
      administered after reperfusion. The initial lesion volumes at 30 minutes post
      ischemia were not significantly different between the two groups (P = 0.92). The
      final infarct volumes two days after stroke increased in the vehicle group but
      decreased in the MB group, yielding a 30% difference in infarct volume (P =
      0.03). Tracking tissue fate on a pixel-by-pixel basis showed that MB salvaged
      more initial core pixels compared to controls (22+/-3% versus 11+/-3%, P = 0.03),
      and more mismatch pixels compared to controls (83+/-3% versus 61+/-8%, P = 0.02).
      This study demonstrates MB treatment minimizes ischemic brain injury and improves
      functional outcomes. 

PMID- 24278192
TI  - The spectral properties of (-)-epigallocatechin 3-O-gallate (EGCG) fluorescence
      in different solvents: dependence on solvent polarity.
AB  - (-)-Epigallocatechin 3-O-gallate (EGCG) a molecule found in green tea and known
      for a plethora of bioactive properties is an inhibitor of heat shock protein 90
      (HSP90), a protein of interest as a target for cancer and neuroprotection.
      Determination of the spectral properties of EGCG fluorescence in environments
      similar to those of binding sites found in proteins provides an important tool to
      directly study protein-EGCG interactions. The goal of this study is to examine
      the spectral properties of EGCG fluorescence in an aqueous buffer (AB) at pH=7.0,
      acetonitrile (AN) (a polar aprotic solvent), dimethylsulfoxide (DMSO) (a polar
      aprotic solvent), and ethanol (EtOH) (a polar protic solvent). We demonstrate
      that EGCG is a highly fluorescent molecule when excited at approximately 275 nm
      with emission maxima between 350 and 400 nm depending on solvent. Another smaller
      excitation peak was found when EGCG is excited at approximately 235 nm with
      maximum emission between 340 and 400 nm. We found that the fluorescence intensity
      (FI) of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85
      times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence
      were determined by solvent polarity. In addition, while the emission maxima of
      EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its
      fluorescence in AN points to non-specific solvent effects on EGCG fluorescence.
      We conclude that significant solvent-dependent changes in both fluorescence
      intensity and fluorescence emission shifts can be effectively used to distinguish
      EGCG in aqueous solutions from EGCG in environments of different polarity, and,
      thus, can be used to study specific EGCG binding to protein binding sites where
      the environment is often different from aqueous in terms of polarity. 

PMID- 24278193
TI  - Genetic factors modulate the impact of pubertal androgen excess on insulin
      sensitivity and fertility.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of
      reproductive age women. The syndrome is caused by a combination of environmental
      influences and genetic predisposition. Despite extensive efforts, the heritable
      factors contributing to PCOS development are not fully understood. The objective
      of this study was to test the hypothesis that genetic background contributes to
      the development of a PCOS-like reproductive and metabolic phenotype in mice
      exposed to excess DHEA during the pubertal transition. We tested whether the PCOS
      phenotype would be more pronounced on the diabetes-prone C57BL/6 background than
      the previously used strain, BALB/cByJ. In addition, we examined strain-dependent
      upregulation of the expression of ovarian and extra-ovarian candidate genes
      implicated in human PCOS, genes containing known strain variants, and genes
      involved with steroidogenesis or insulin sensitivity. These studies show that
      there are significant strain-related differences in metabolic response to excess
      androgen exposure during puberty. Additionally, our results suggest the C57BL/6J
      strain provides a more robust and uniform experimental platform for PCOS research
      than the BALB/cByJ strain. 

PMID- 24278194
TI  - Depression-related work disability: socioeconomic inequalities in onset, duration
      and recurrence.
AB  - OBJECTIVE: Depression is a major cause of disability in working populations and
      the reduction of socioeconomic inequalities in disability is an important public
      health challenge. We examined work disability due to depression with four
      indicators of socioeconomic status. METHODS: A prospective cohort study of 125
      355 Finnish public sector employees was linked to national register data on work
      disability (>9 days) due to depressive disorders (International Classification of
      Diseases, codes F32-F34) from January 2005 to December 2011. Primary outcomes
      were the onset of work disability due to depressive disorders and, among those
      with such disability, return to work after and recurrent episodes of work
      disability due to depression. RESULTS: We found a consistent inverse
      socioeconomic gradient in work disability due to depression. Lower occupational
      position, lower educational level, smaller residence size, and rented (vs. owner
      occupied) residence were all associated with an increased risk of work
      disability. Return to work was slower for employees with basic education
      (cumulative odds ratio = 1.21, 95% CI: 1.05-1.39) compared to those with higher
      education. Recurrent work disability episodes due to depression were less common
      among upper-grade non-manual workers (the highest occupational group) than among
      lower-grade non-manual (hazard ratio = 1.16, 95% CI: 1.07-1.25) and manual
      (hazard ratio = 1.14, 95% CI: 1.02-1.26) workers. CONCLUSIONS: These data from
      Finnish public sector employees show persistent socioeconomic inequalities in
      work disability due to depression from 2005 to 2011 in terms of onset, recovery
      and recurrence.

PMID- 24278196
TI  - Is chytridiomycosis driving Darwin's frogs to extinction?
AB  - Darwin's frogs (Rhinoderma darwinii and R. rufum) are two species of mouth
      brooding frogs from Chile and Argentina that have experienced marked population
      declines. Rhinoderma rufum has not been found in the wild since 1980. We
      investigated historical and current evidence of Batrachochytrium dendrobatidis
      (Bd) infection in Rhinoderma spp. to determine whether chytridiomycosis is
      implicated in the population declines of these species. Archived and live
      specimens of Rhinoderma spp., sympatric amphibians and amphibians at sites where
      Rhinoderma sp. had recently gone extinct were examined for Bd infection using
      quantitative real-time PCR. Six (0.9%) of 662 archived anurans tested positive
      for Bd (4/289 R. darwinii; 1/266 R. rufum and 1/107 other anurans), all of which
      had been collected between 1970 and 1978. An overall Bd-infection prevalence of
      12.5% was obtained from 797 swabs taken from 369 extant individuals of R.
      darwinii and 428 individuals representing 18 other species of anurans found at
      sites with current and recent presence of the two Rhinoderma species. In extant
      R. darwinii, Bd-infection prevalence (1.9%) was significantly lower than that
      found in other anurans (7.3%). The prevalence of infection (30%) in other
      amphibian species was significantly higher in sites where either Rhinoderma spp.
      had become extinct or was experiencing severe population declines than in sites
      where there had been no apparent decline (3.0%; x(2) = 106.407, P<0.001). This is
      the first report of widespread Bd presence in Chile and our results are
      consistent with Rhinoderma spp. declines being due to Bd infection, although
      additional field and laboratory investigations are required to investigate this
      further.

PMID- 24278195
TI  - Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in
      patients with type 1 diabetes.
AB  - OBJECTIVES: Follicular helper T (Tfh) cells exert an important role in autoimmune
      diseases. Whether it might be involved in type 1 diabetes (T1D) is unknown. Our
      aim was to investigate the role of Tfh cells in patients with T1D and the effect
      of anti-CD20 monoclonal antibody (rituximab) on Tfh cells from T1D patients.
      PATIENTS AND METHODS: Fifty-four patients with T1D and 37 healthy controls were
      enrolled in the current study. 20 of those patients were treated with rituximab.
      The frequencies of circulating CD4(+)CXCR5(+)ICOS(+)T cells were analyzed by flow
      cytometry. The serum autoantibodies were detected by radioligand assay. The
      levels of IL-21, IL-6 and BCL-6 were assessed using ELISA and/or real-time PCR.
      RESULTS: Increased frequencies of circulating Tfh cells together with enhanced
      expression of IL-21 were detected in patients. The correlation between the
      frequencies of circulating Tfh cells and the serum autoantibodies or C-peptide
      level was comfirmed. After rituximab therapy, follow-up analysis demonstrated
      that the frequencies of circulating Tfh cell and serum IA2A were decreased. The
      levels of IL-21, IL-6 and Bcl-6 mRNA were decreased after treatment. Furthermore,
      beta cell function in 10 of 20 patients was improved. CONCLUSIONS: These data
      indicate Tfh cells may participate in the T1D-relatede immune responses and B
      cells might play a role in the development of Tfh responses in the disease
      progression.

PMID- 24278197
TI  - PCaAnalyser: a 2D-image analysis based module for effective determination of
      prostate cancer progression in 3D culture.
AB  - Three-dimensional (3D) in vitro cell based assays for Prostate Cancer (PCa)
      research are rapidly becoming the preferred alternative to that of conventional
      2D monolayer cultures. 3D assays more precisely mimic the microenvironment found
      in vivo, and thus are ideally suited to evaluate compounds and their suitability
      for progression in the drug discovery pipeline. To achieve the desired high
      throughput needed for most screening programs, automated quantification of 3D
      cultures is required. Towards this end, this paper reports on the development of
      a prototype analysis module for an automated high-content-analysis (HCA) system,
      which allows for accurate and fast investigation of in vitro 3D cell culture
      models for PCa. The Java based program, which we have named PCaAnalyser, uses
      novel algorithms that allow accurate and rapid quantitation of protein expression
      in 3D cell culture. As currently configured, the PCaAnalyser can quantify a range
      of biological parameters including: nuclei-count, nuclei-spheroid membership
      prediction, various function based classification of peripheral and non
      peripheral areas to measure expression of biomarkers and protein constituents
      known to be associated with PCa progression, as well as defining segregate
      cellular-objects effectively for a range of signal-to-noise ratios. In addition,
      PCaAnalyser architecture is highly flexible, operating as a single independent
      analysis, as well as in batch mode; essential for High-Throughput-Screening
      (HTS). Utilising the PCaAnalyser, accurate and rapid analysis in an automated
      high throughput manner is provided, and reproducible analysis of the distribution
      and intensity of well-established markers associated with PCa progression in a
      range of metastatic PCa cell-lines (DU145 and PC3) in a 3D model demonstrated. 

PMID- 24278198
TI  - Tree biomass estimation of Chinese fir (Cunninghamia lanceolata) based on
      Bayesian method.
AB  - Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) is the most important conifer
      species for timber production with huge distribution area in southern China.
      Accurate estimation of biomass is required for accounting and monitoring Chinese
      forest carbon stocking. In the study, allometric equation W = a(D2H)b was used to
      analyze tree biomass of Chinese fir. The common methods for estimating allometric
      model have taken the classical approach based on the frequency interpretation of
      probability. However, many different biotic and abiotic factors introduce
      variability in Chinese fir biomass model, suggesting that parameters of biomass
      model are better represented by probability distributions rather than fixed
      values as classical method. To deal with the problem, Bayesian method was used
      for estimating Chinese fir biomass model. In the Bayesian framework, two priors
      were introduced: non-informative priors and informative priors. For informative
      priors, 32 biomass equations of Chinese fir were collected from published
      literature in the paper. The parameter distributions from published literature
      were regarded as prior distributions in Bayesian model for estimating Chinese fir
      biomass. Therefore, the Bayesian method with informative priors was better than
      non-informative priors and classical method, which provides a reasonable method
      for estimating Chinese fir biomass.

PMID- 24278199
TI  - Non-transferrin-bound iron (NTBI) uptake by T lymphocytes: evidence for the
      selective acquisition of oligomeric ferric citrate species.
AB  - Iron is an essential nutrient in several biological processes such as oxygen
      transport, DNA replication and erythropoiesis. Plasma iron normally circulates
      bound to transferrin. In iron overload disorders, however, iron concentrations
      exceed transferrin binding capacity and iron appears complexed with low molecular
      weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible
      for the toxicity associated with iron-overload pathologies but the mechanisms
      leading to NTBI uptake are not fully understood. Here we show for the first time
      that T lymphocytes are able to take up and accumulate NTBI in a manner that
      resembles that of hepatocytes. Moreover, we show that both hepatocytes and T
      lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate
      species, suggesting the existence of a selective NTBI carrier. These results
      provide a tool for the identification of the still elusive ferric-citrate
      cellular carrier and may also open a new pathway towards the design of more
      efficient iron chelators for the treatment of iron overload disorders. 

PMID- 24278200
TI  - Phenotypic and transcriptional fidelity of patient-derived colon cancer
      xenografts in immune-deficient mice.
AB  - Xenografts of human colorectal cancer (CRC) in immune-deficient mice have great
      potential for accelerating the study of tumor biology and therapy. We evaluated
      xenografts established in NOD/scid/IL2Rgamma-null mice from the primary or
      metastatic tumors of 27 patients with CRC to estimate their capacity for
      expanding tumor cells for in vitro studies and to assess how faithfully they
      recapitulated the transcriptional profile of their parental tumors. RNA-seq
      analysis of parental human CRC tumors and their derivative xenografts
      demonstrated that reproducible transcriptional changes characterize the human
      tumor to murine xenograft transition. In most but not all cases, the human
      stroma, vasculature, and hematopoietic elements were systematically replaced by
      murine analogues while the carcinoma component persisted. Once established as
      xenografts, human CRC cells that could be propagated by serial transplantation
      remained transcriptionally stable. Three histologically atypical xenografts,
      established from patients with peritoneal metastases, contained abundant human
      stromal elements and blood vessels in addition to human tumor cells. The
      transcriptomes of these mixed tumor/stromal xenografts did not closely resemble
      those of their parental tumors, and attempts to propagate such xenografts by
      serial transplantation were unsuccessful. Stable expression of numerous genes
      previously identified as high priority targets for immunotherapy was observed in
      most xenograft lineages. Aberrant expression in CRC cells of human genes that are
      normally only expressed in hematopoietic cells was also observed. Our results
      suggest that human CRC cells expanded in murine xenografts have great utility for
      studies of tumor immunobiology and targeted therapies such as immunotherapy but
      also identify potential limitations. 

PMID- 24278201
TI  - Human sensorimotor communication: a theory of signaling in online social
      interactions.
AB  - Although the importance of communication is recognized in several disciplines, it
      is rarely studied in the context of online social interactions and joint actions.
      During online joint actions, language and gesture are often insufficient and
      humans typically use non-verbal, sensorimotor forms of communication to send
      coordination signals. For example, when playing volleyball, an athlete can
      exaggerate her movements to signal her intentions to her teammates (say, a pass
      to the right) or to feint an adversary. Similarly, a person who is transporting a
      table together with a co-actor can push the table in a certain direction to
      signal where and when he intends to place it. Other examples of "signaling" are
      over-articulating in noisy environments and over-emphasizing vowels in child
      directed speech. In all these examples, humans intentionally modify their action
      kinematics to make their goals easier to disambiguate. At the moment no formal
      theory exists of these forms of sensorimotor communication and signaling. We
      present one such theory that describes signaling as a combination of a pragmatic
      and a communicative action, and explains how it simplifies coordination in online
      social interactions. We cast signaling within a "joint action optimization"
      framework in which co-actors optimize the success of their interaction and joint
      goals rather than only their part of the joint action. The decision of whether
      and how much to signal requires solving a trade-off between the costs of
      modifying one's behavior and the benefits in terms of interaction success.
      Signaling is thus an intentional strategy that supports social interactions; it
      acts in concert with automatic mechanisms of resonance, prediction, and
      imitation, especially when the context makes actions and intentions ambiguous and
      difficult to read. Our theory suggests that communication dynamics should be
      studied within theories of coordination and interaction rather than only in terms
      of the maximization of information transmission. 

PMID- 24278202
TI  - Mining genes involved in insecticide resistance of Liposcelis bostrychophila
      Badonnel by transcriptome and expression profile analysis.
AB  - BACKGROUND: Recent studies indicate that infestations of psocids pose a new risk
      for global food security. Among the psocids species, Liposcelis bostrychophila
      Badonnel has gained recognition in importance because of its parthenogenic
      reproduction, rapid adaptation, and increased worldwide distribution. To date,
      the molecular data available for L. bostrychophila is largely limited to genes
      identified through homology. Also, no transcriptome data relevant to psocids
      infection is available. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we
      generated de novo assembly of L. bostrychophila transcriptome performed through
      the short read sequencing technology (Illumina). In a single run, we obtained
      more than 51 million sequencing reads that were assembled into 60,012 unigenes
      (mean size = 711 bp) by Trinity. The transcriptome sequences from different
      developmental stages of L. bostrychophila including egg, nymph and adult were
      annotated with non-redundant (Nr) protein database, gene ontology (GO), cluster
      of orthologous groups of proteins (COG), and KEGG orthology (KO). The analysis
      revealed three major enzyme families involved in insecticide metabolism as
      differentially expressed in the L. bostrychophila transcriptome. A total of 49
      P450-, 31 GST- and 21 CES-specific genes representing the three enzyme families
      were identified. Besides, 16 transcripts were identified to contain target site
      sequences of resistance genes. Furthermore, we profiled gene expression patterns
      upon insecticide (malathion and deltamethrin) exposure using the tag-based
      digital gene expression (DGE) method. CONCLUSION: The L. bostrychophila
      transcriptome and DGE data provide gene expression data that would further our
      understanding of molecular mechanisms in psocids. In particular, the findings of
      this investigation will facilitate identification of genes involved in
      insecticide resistance and designing of new compounds for control of psocids.

PMID- 24278203
TI  - The economic burden of meningitis to households in Kassena-Nankana district of
      Northern Ghana.
AB  - OBJECTIVE: To estimate the direct and indirect costs of meningitis to households
      in the Kassena-Nankana District of Ghana. METHODS: A Cost of illness (COI) survey
      was conducted between 2010 and 2011. The COI was computed from a retrospective
      review of 80 meningitis cases answers to questions about direct medical costs,
      direct non-medical costs incurred and productivity losses due to recent
      meningitis incident. RESULTS: The average direct and indirect costs of treating
      meningitis in the district was GHc152.55 (US$101.7) per household. This is
      equivalent to about two months minimum wage earned by Ghanaians in unskilled paid
      jobs in 2009. Households lost 29 days of work per meningitis case and thus those
      in minimum wage paid jobs lost a monthly minimum wage of GHc76.85 (US$51.23) due
      to the illness. Patients who were insured spent an average of GHc38.5 (US$25.67)
      in direct medical costs whiles the uninsured patients spent as much as GHc177.9
      (US$118.6) per case. Patients with sequelae incurred additional costs of GHc22.63
      (US$15.08) per case. The least poor were more exposed to meningitis than the
      poorest. CONCLUSION: Meningitis is a debilitating but preventable disease that
      affects people living in the Sahel and in poorer conditions. The cost of
      meningitis treatment may further lead to impoverishment for these households.
      Widespread mass vaccination will save households' an equivalent of GHc175.18
      (US$117) and impairment due to meningitis.

PMID- 24278204
TI  - Evaluation of paeonol skin-target delivery from its microsponge formulation: in
      vitro skin permeation and in vivo microdialysis.
AB  - The aim of the present study was to design a novel topical skin-target drug
      delivery system, the paeonol microsponge, and to investigate its drug-release
      patterns in dosage form, both in vitro and in vivo. Paeonol microsponges were
      prepared using the quasi-emulsion solvent-diffusion method. In vitro release
      studies were carried out using Franz diffusion cells, while in vivo studies were
      investigated by microdialysis after the paeonol microsponges were incorporated
      into a cream base. In vitro release studies showed that the drug delivered via
      microsponges increased the paeonol permeation rate. Ex vivo drug-deposition
      studies showed that the microsponge formulation improved drug residence in skin.
      In addition, in vivo microdialysis showed that the values for the area under the
      concentration versus time curve (AUC) for the paeonol microsponge cream was much
      higher than that of paeonol cream without microsponges. Maximum time (Tmax) was
      220 min for paeonol microsponge cream and 480 min for paeonol cream, while the
      half-life (t1/2) of paeonol microsponge cream (935.1 min) was almost twice that
      of paeonol cream (548.6 min) in the skin (n = 3). Meanwhile, in the plasma, the
      AUC value for paeonol microsponge cream was half that of the paeonol cream. Based
      on these results, paeonol-loaded microsponge formulations could be a better
      alternative for treating skin disease, as the formulation increases drug
      bioavailability by lengthening the time of drug residence in the skin and should
      reduce side-effects because of the lower levels of paeonol moving into the
      circulation. 

PMID- 24278206
TI  - Clinical course of ophthalmic findings and potential influence factors of
      herpesvirus infections: 18 month follow-up of a closed herd of lipizzaners.
AB  - BACKGROUND: To date the influence of herpesviruses on the development of equine
      ocular diseases has not been clearly determined. OBJECTIVE: The purpose of this
      study was to illustrate the course of equine ocular findings over a period of 18
      months at 6 month intervals, in correlation with the results of herpesvirus
      detection. METHODS: 266 Lipizzaners in 3 federal states of Austria underwent
      complete ophthalmologic examination 4 times. Blood samples, nasal- and
      conjunctival swabs were obtained at the same time and used for the detection of
      the equid gammaherpesviruses EHV-2 and EHV-5 using consensus herpesvirus PCR and
      type-specific qPCRs. Ophthalmic findings and results of herpesvirus PCRs were
      recorded and statistically analysed using one-way ANOVA, and multiple logistic
      regression analysis to determine the influence of herpesvirus infections and
      other contributing factors on the presence of ophthalmic findings. RESULTS: In
      the first, second, third and fourth examination period 266, 261, 249 and 230
      horses were included, respectively. Ophthalmic findings consistent with
      herpesvirus infections included conjunctival- and corneal pathologies.
      Statistical analysis revealed that the probability of positive herpesvirus PCR
      results decreased with progressing age; however the presence of corneal findings
      increased over time. At the time of each examination 45.1%, 41.8%, 43.0%, and
      57.0% of horses with conjunctival or corneal findings, respectively, were
      positive for EHV-2 and/or EHV-5. However, 31.6%, 17.6%, 20.1%, and 13.0% of
      clinically sound horses were positive for these herpesviruses at each examination
      period, too. CONCLUSION: Based on the results of our study there is a significant
      influence of young age on EHV-2 and/or EHV-5 infection. Corneal pathologies
      increased over time and with progressing age. Whether the identified findings
      were caused by herpesviruses could not be unequivocally determined.

PMID- 24278205
TI  - Combined miRNA and mRNA signature identifies key molecular players and pathways
      involved in chikungunya virus infection in human cells.
AB  - Since its discovery, Chikungunya fever caused by a virus (CHIKV) has ravaged most
      of Africa and Southeast Asia. Despite there being more than a million reported
      cases in India alone and the seriousness of the disease in the chronic phase, a
      clear understanding of the disease pathogenesis and host response remains
      elusive. Here, we use microarray technology and quantitative PCR method to
      establish the complete miRNA, snoRNA and mRNA signature of host response upon
      CHIKV infection in human cell line infection model, HEK293T. The results were
      further validated in human primary cells (dermal fibroblasts). miRNA expression
      profiling revealed regulation of 152 miRNAs post CHIKV infection. An interesting
      overlap in miRNA signature was seen majorly with HCV, HPV and HIV1 virus. The
      microarray data further validated by qRT-PCR revealed induction of miR-744, miR
      638, miR-503 and others among the top upregulated miRNAs. Notably, we found
      induction of snoRNAs belonging to C/D cluster including close paralogs of U3,
      U44, U76 and U78 snoRNAs. Genes were found to be differentially expressed along 3
      major pathways; TGF-beta, endocytosis and the cell cycle pathways. qRT-PCR data
      confirmed strong induction of TGF-beta (SMAD6, JUN, SKIL) and endocytosis pathway
      (CXCR4, HSPA8, ADRB1) genes while downregulation of cell cycle genes (CDC27 and
      CDC23). Interestingly, use of TGF-beta inhibitor, SB-431542, increased CHIKV
      mediated cell death. Overall, this study aims at providing the first complete
      transcriptome signature of host response upon CHIKV infection to aid
      identification of possible biomarkers and therapeutic targets. 

PMID- 24278207
TI  - Iron limitation modulates ocean acidification effects on southern ocean
      phytoplankton communities.
AB  - The potential interactive effects of iron (Fe) limitation and Ocean Acidification
      in the Southern Ocean (SO) are largely unknown. Here we present results of a long
      term incubation experiment investigating the combined effects of CO2 and Fe
      availability on natural phytoplankton assemblages from the Weddell Sea,
      Antarctica. Active Chl a fluorescence measurements revealed that we successfully
      cultured phytoplankton under both Fe-depleted and Fe-enriched conditions. Fe
      treatments had significant effects on photosynthetic efficiency (Fv/Fm; 0.3 for
      Fe-depleted and 0.5 for Fe-enriched conditions), non-photochemical quenching
      (NPQ), and relative electron transport rates (rETR). pCO2 treatments
      significantly affected NPQ and rETR, but had no effect on Fv/Fm. Under Fe
      limitation, increased pCO2 had no influence on C fixation whereas under Fe
      enrichment, primary production increased with increasing pCO2 levels. These CO2
      dependent changes in productivity under Fe-enriched conditions were accompanied
      by a pronounced taxonomic shift from weakly to heavily silicified diatoms (i.e.
      from Pseudo-nitzschia sp. to Fragilariopsis sp.). Under Fe-depleted conditions,
      this functional shift was absent and thinly silicified species dominated all pCO2
      treatments (Pseudo-nitzschia sp. and Synedropsis sp. for low and high pCO2,
      respectively). Our results suggest that Ocean Acidification could increase
      primary productivity and the abundance of heavily silicified, fast sinking
      diatoms in Fe-enriched areas, both potentially leading to a stimulation of the
      biological pump. Over much of the SO, however, Fe limitation could restrict this
      possible CO2 fertilization effect. 

PMID- 24278208
TI  - Differential phosphoproteome regulation of nucleus accumbens in environmentally
      enriched and isolated rats in response to acute stress.
AB  - Increasing evidence shows that stress contributes to the pathogenesis of major
      depressive disorder which is a severe neuropsychiatric disorder and influences
      over 10% of the world's population. Our previous studies revealed that rats
      reared in an enriched environment display less depression-related behavior
      compared to rats raised in an isolated environment, which implies that
      environmental enrichment produces an antidepressant-like behavioral phenotype.
      However, the molecular mechanisms are not fully understood. Protein
      phosphorylation rapidly changes signaling pathway function and alters the
      function of proteins associated with the stress-induced depressive disorder.
      Thus, in this study, a phosphoproteomic approach was used to uncover differential
      phosphoprotein regulation in rat nucleus accumbens between isolated (IC) and
      enriched environmental conditions (EC) under basal conditions, and in response to
      acute stress. We found 23 phosphoproteins were regulated in EC vs. IC rats under
      basal conditions; 10 phosphoproteins regulated by stress in IC rats; and 15
      regulated by stress in EC rats. Among all significantly regulated
      phosphoproteins, 11 of them were represented in at least two conditions. The
      regulated phosphoproteins represent signaling pathway proteins (including ERK2),
      enzymes, transcriptional regulators, protein translation regulators,
      transporters, chaperones and cytoskeletal proteins. These findings provide a
      global view for further understanding the contribution of protein phosphorylation
      in depression pathogenesis and antidepressant action. 

PMID- 24278210
TI  - Exposure of unwounded plants to chemical cues associated with herbivores leads to
      exposure-dependent changes in subsequent herbivore attack.
AB  - Although chemical predator cues often lead to changes in the anti-predator
      behavior of animal prey, it is not clear whether non-volatile herbivore
      kairomones (i.e. incidental chemical cues produced by herbivore movement or
      metabolism but not produced by an attack) trigger the induction of defense in
      plants prior to attack. I found that unwounded plants (Brassica nigra) that were
      regularly exposed to kairomones from snails (mucus and feces produced during
      movement of Helix aspersa) subsequently experienced reduced rates of attack by
      snails, unlike unwounded plants that received only one initial early exposure to
      snail kairomones. A follow-up experiment found that mucus alone did not affect
      snail feeding on previously harvested B. oleracea leaves, suggesting that changes
      in herbivory on B. nigra were due to changes in plant quality. The finding that
      chemicals associated with herbivores leads to changes in palatability of
      unwounded plants suggests that plants eavesdrop on components of non-volatile
      kairomones of their snail herbivores. Moreover, this work shows that the nature
      of plant exposure matters, supporting the conclusion that plants that have not
      been attacked or wounded nonetheless tailor their use of defenses based on
      incidental chemical information associated with herbivores and the timing with
      which cues of potential attack are encountered. 

PMID- 24278209
TI  - Functional and genomic analyses of alpha-solenoid proteins.
AB  - Alpha-solenoids are flexible protein structural domains formed by ensembles of
      alpha-helical repeats (Armadillo and HEAT repeats among others). While homology
      can be used to detect many of these repeats, some alpha-solenoids have very
      little sequence homology to proteins of known structure and we expect that many
      remain undetected. We previously developed a method for detection of alpha
      helical repeats based on a neural network trained on a dataset of protein
      structures. Here we improved the detection algorithm and updated the training
      dataset using recently solved structures of alpha-solenoids. Unexpectedly, we
      identified occurrences of alpha-solenoids in solved protein structures that
      escaped attention, for example within the core of the catalytic subunit of PI3KC.
      Our results expand the current set of known alpha-solenoids. Application of our
      tool to the protein universe allowed us to detect their significant enrichment in
      proteins interacting with many proteins, confirming that alpha-solenoids are
      generally involved in protein-protein interactions. We then studied the taxonomic
      distribution of alpha-solenoids to discuss an evolutionary scenario for the
      emergence of this type of domain, speculating that alpha-solenoids have emerged
      in multiple taxa in independent events by convergent evolution. We observe a
      higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic
      families, such as Cyanobacteria and Planctomycetes, which could be associated to
      increased cellular complexity. The method is available at http://cbdm.mdc
      berlin.de/~ard2/. 

PMID- 24278211
TI  - Comparison of HER2 and phospho-HER2 expression between biopsy and resected breast
      cancer specimens using a quantitative assessment method.
AB  - BACKGROUND: HER2/Neu (ErbB-2) overexpression, which occurs in 15-20% of breast
      cancer cases, is associated with better response to treatment with the drug
      trastuzumab. PhosphoHER2 (pHER2) has been evaluated for prediction of response to
      trastuzumab. Both markers are heterogeneously detected and are potentially
      subject to loss as a consequence of delayed time to fixation. Here, we
      quantitatively assess both markers in core needle biopsies (CNBs) and matched
      tumor resections to assess concordance between the core and the resection and
      between HER2 and pHER2. METHODS: A selected retrospective collection of archival
      breast cancer cases yielded 67 cases with both core and resection specimens. Both
      HER2 and pTyr(1248)HER2 were analyzed by the AQUA(r) method of quantitative
      immunofluorescence on each specimen pair. RESULTS: Both HER2 immunoreactivity
      (P<0.0001) and pTyr(1248)HER2 immunoreactivity (P<0.0001) were lower in
      resections relative to CNB specimens. However, clinical implications of this
      change may not be evident since no case changed from 3+ (CNB) to negative
      (resection). Assessment of pTyr(1248)HER2 showed no direct correlation with HER2
      in either CNB or resection specimens. CONCLUSIONS: The data suggest that
      measurement of both HER2 and phospho- Tyr(1248)HER2, in formalin-fixed tissue by
      immunological methods is significantly affected by pre-analytic variables. The
      current study warrants the adequate handling of resected specimens for the
      reproducible evaluation of HER2 and pHER2. The level of pTyr(1248)HER2, was not
      correlated to total HER2 protein. Further studies are required to determine the
      significance of these observations with respect to response to HER2 directed
      therapies.

PMID- 24278212
TI  - lambda Phage nanobioparticle expressing apoptin efficiently suppress human breast
      carcinoma tumor growth in vivo.
AB  - Using phages is a novel field of cancer therapy and phage nanobioparticles (NBPs)
      such as lambda phage could be modified to deliver and express genetic cassettes
      into eukaryotic cells safely in contrast with animal viruses. Apoptin, a protein
      from chicken anemia virus (CAV) has the ability to specifically induce apoptosis
      only in carcinoma cells. We presented a safe method of breast tumor therapy via
      the apoptin expressing lambda NBPs. Here, we constructed a lambda ZAP-CMV-apoptin
      recombinant NBP and investigated the effectiveness of its apoptotic activity on
      BT-474, MDA-MB-361, SKBR-3, UACC-812 and ZR-75 cell lines that over-expressing
      her-2 marker. Apoptosis was evaluated via annexin-V fluorescent iso
      thiocyanate/propidium iodide staining, flow-cytometric method and TUNEL assay.
      Transfection with NBPs carrying lambda ZAP-CMV-apoptin significantly inhibited
      growth of all the breast carcinoma cell lines in vitro. Also nude mice model
      implanted BT-474 human breast tumor was successfully responded to the systemic
      and local injection of untargeted recombinant lambda NBPs. The results presented
      here reveal important features of recombinant lambda nanobioparticles to serve as
      safe delivery and expression platform for human cancer therapy. 

PMID- 24278213
TI  - Cortical reorganization after hand immobilization: the beta qEEG spectral
      coherence evidences.
AB  - There is increasing evidence that hand immobilization is associated with various
      changes in the brain. Indeed, beta band coherence is strongly related to motor
      act and sensitive stimuli. In this study we investigate the electrophysiological
      and cortical changes that occur when subjects are submitted to hand
      immobilization. We hypothesized that beta coherence oscillations act as a
      mechanism underlying inter- and intra-hemispheric changes. As a methodology for
      our study fifteen healthy individuals between the ages of 20 and 30 years were
      subjected to a right index finger task before and after hand immobilization while
      their brain activity pattern was recorded using quantitative
      electroencephalography. This analysis revealed that hand immobilization caused
      changes in frontal, central and parietal areas of the brain. The main findings
      showed a lower beta-2 band in frontal regions and greater cortical activity in
      central and parietal areas. In summary, the coherence increased in the frontal,
      central and parietal cortex, due to hand immobilization and it adjusted the
      brains functioning, which had been disrupted by the procedure. Moreover, the
      brain adaptation upon hand immobilization of the subjects involved inter- and
      intra-hemispheric changes. 

PMID- 24278214
TI  - Complex network analysis of CA3 transcriptome reveals pathogenic and compensatory
      pathways in refractory temporal lobe epilepsy.
AB  - We previously described - studying transcriptional signatures of hippocampal CA3
      explants - that febrile (FS) and afebrile (NFS) forms of refractory mesial
      temporal lobe epilepsy constitute two distinct genomic phenotypes. That network
      analysis was based on a limited number (hundreds) of differentially expressed
      genes (DE networks) among a large set of valid transcripts (close to two tens of
      thousands). Here we developed a methodology for complex network visualization
      (3D) and analysis that allows the categorization of network nodes according to
      distinct hierarchical levels of gene-gene connections (node degree) and of
      interconnection between node neighbors (concentric node degree). Hubs are highly
      connected nodes, VIPs have low node degree but connect only with hubs, and high
      hubs have VIP status and high overall number of connections. Studying the whole
      set of CA3 valid transcripts we: i) obtained complete transcriptional networks
      (CO) for FS and NFS phenotypic groups; ii) examined how CO and DE networks are
      related; iii) characterized genomic and molecular mechanisms underlying FS and
      NFS phenotypes, identifying potential novel targets for therapeutic
      interventions. We found that: i) DE hubs and VIPs are evenly distributed inside
      the CO networks; ii) most DE hubs and VIPs are related to synaptic transmission
      and neuronal excitability whereas most CO hubs, VIPs and high hubs are related to
      neuronal differentiation, homeostasis and neuroprotection, indicating
      compensatory mechanisms. Complex network visualization and analysis is a useful
      tool for systems biology approaches to multifactorial diseases. Network
      centrality observed for hubs, VIPs and high hubs of CO networks, is consistent
      with the network disease model, where a group of nodes whose perturbation leads
      to a disease phenotype occupies a central position in the network. Conceivably,
      the chance for exerting therapeutic effects through the modulation of particular
      genes will be higher if these genes are highly interconnected in transcriptional
      networks. 

PMID- 24278215
TI  - IQ domain GTPase-activating protein 1 is involved in shear stress-induced
      progenitor-derived endothelial cell alignment.
AB  - Shear stress is one of mechanical constraints which are exerted by blood flow on
      endothelial cells (ECs). To adapt to shear stress, ECs align in the direction of
      flow through adherens junction (AJ) remodeling. However, mechanisms regulating
      ECs alignment under shear stress are poorly understood. The scaffold protein IQ
      domain GTPase activating protein 1 (IQGAP1) is a scaffold protein which couples
      cell signaling to the actin and microtubule cytoskeletons and is involved in cell
      migration and adhesion. IQGAP1 also plays a role in AJ organization in epithelial
      cells. In this study, we investigated the potential IQGAP1 involvement in the
      endothelial cells alignment under shear stress. Progenitor-derived endothelial
      cells (PDECs), transfected (or not) with IQGAP1 small interfering RNA, were
      exposed to a laminar shear stress (1.2 N/m(2)) and AJ proteins (VE-cadherin and
      beta-catenin) and IQGAP1 were labeled by immunofluorescence. We show that IQGAP1
      is essential for ECs alignment under shear stress. We studied the role of IQGAP1
      in AJs remodeling of PDECs exposed to shear stress by studying cell localization
      and IQGAP1 interactions with VE-cadherin and beta-catenin by immunofluorescence
      and Proximity Ligation Assays. In static conditions, IQGAP1 interacts with VE
      cadherin but not with beta-catenin at the cell membrane. Under shear stress,
      IQGAP1 lost its interaction from VE-cadherin to beta-catenin. This "switch" was
      concomitant with the loss of beta-catenin/VE-cadherin interaction at the cell
      membrane. This work shows that IQGAP1 is essential to ECs alignment under shear
      stress and that AJ remodeling represents one of the mechanisms involved. These
      results provide a new approach to understand ECs alignment under to shear stress.

PMID- 24278216
TI  - Plant-based production of recombinant Plasmodium surface protein pf38 and
      evaluation of its potential as a vaccine candidate.
AB  - Pf38 is a surface protein of the malarial parasite Plasmodium falciparum. In this
      study, we produced and purified recombinant Pf38 and a fusion protein composed of
      red fluorescent protein and Pf38 (RFP-Pf38) using a transient expression system
      in the plant Nicotiana benthamiana. To our knowledge, this is the first
      description of the production of recombinant Pf38. To verify the quality of the
      recombinant Pf38, plasma from semi-immune African donors was used to confirm
      specific binding to Pf38. ELISA measurements revealed that immune responses to
      Pf38 in this African subset were comparable to reactivities to AMA-1 and MSP119.
      Pf38 and RFP-Pf38 were successfully used to immunise mice, although titres from
      these mice were low (on average 1?11.000 and 1?39.000, respectively). In immune
      fluorescence assays, the purified IgG fraction from the sera of immunised mice
      recognised Pf38 on the surface of schizonts, gametocytes, macrogametes and
      zygotes, but not sporozoites. Growth inhibition assays using alphaPf38 antibodies
      demonstrated strong inhibition (>=60%) of the growth of blood-stage P.
      falciparum. The development of zygotes was also effectively inhibited by
      alphaPf38 antibodies, as determined by the zygote development assay.
      Collectively, these results suggest that Pf38 is an interesting candidate for the
      development of a malaria vaccine. 

PMID- 24278217
TI  - Resequencing three candidate genes for major depressive disorder in a Dutch
      cohort.
AB  - Major depressive disorder (MDD) is a psychiatric disorder, characterized by
      periods of low mood of more than two weeks, loss of interest in normally
      enjoyable activities and behavioral changes. MDD is a complex disorder and does
      not have a single genetic cause. In 2009 a genome wide association study (GWAS)
      was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS
      mapped to a region spanning the gene PCLO, and the non-synonymous coding single
      nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide
      significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and
      SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic
      variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort
      and performed association analysis to investigate if rs2522833 is the causal
      variant or simply in linkage disequilibrium with a more associated variant. GRM7
      and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather
      more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort
      or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4
      with a higher association in this cohort. After next generation sequencing and
      association analysis we excluded the possibility of an undetected common variant
      to be more associated. For neither PCLO nor GRM7 we found a more associated
      variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07)
      than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide
      significance was found. Although we did not take into account rare variants, we
      conclude that our results provide further support for the hypothesis that the non
      synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the
      causal variant in the GAIN-MDD cohort. 

PMID- 24278218
TI  - DNA sequences at a glance.
AB  - Data summarization and triage is one of the current top challenges in visual
      analytics. The goal is to let users visually inspect large data sets and examine
      or request data with particular characteristics. The need for summarization and
      visual analytics is also felt when dealing with digital representations of DNA
      sequences. Genomic data sets are growing rapidly, making their analysis
      increasingly more difficult, and raising the need for new, scalable tools. For
      example, being able to look at very large DNA sequences while immediately
      identifying potentially interesting regions would provide the biologist with a
      flexible exploratory and analytical tool. In this paper we present a new concept,
      the "information profile", which provides a quantitative measure of the local
      complexity of a DNA sequence, independently of the direction of processing. The
      computation of the information profiles is computationally tractable: we show
      that it can be done in time proportional to the length of the sequence. We also
      describe a tool to compute the information profiles of a given DNA sequence, and
      use the genome of the fission yeast Schizosaccharomyces pombe strain 972 h(-) and
      five human chromosomes 22 for illustration. We show that information profiles are
      useful for detecting large-scale genomic regularities by visual inspection.
      Several discovery strategies are possible, including the standalone analysis of
      single sequences, the comparative analysis of sequences from individuals from the
      same species, and the comparative analysis of sequences from different organisms.
      The comparison scale can be varied, allowing the users to zoom-in on specific
      details, or obtain a broad overview of a long segment. Software applications have
      been made available for non-commercial use at
      http://bioinformatics.ua.pt/software/dna-at-glance. 

PMID- 24278219
TI  - Classification of forefoot plantar pressure distribution in persons with
      diabetes: a novel perspective for the mechanical management of diabetic foot?
AB  - BACKGROUND: The aim of this study was to identify groups of subjects with similar
      patterns of forefoot loading and verify if specific groups of patients with
      diabetes could be isolated from non-diabetics. METHODOLOGY/PRINCIPAL FINDINGS:
      Ninety-seven patients with diabetes and 33 control participants between 45 and 70
      years were prospectively recruited in two Belgian Diabetic Foot Clinics. Barefoot
      plantar pressure measurements were recorded and subsequently analysed using a
      semi-automatic total mapping technique. Kmeans cluster analysis was applied on
      relative regional impulses of six forefoot segments in order to pursue a
      classification for the control group separately, the diabetic group separately
      and both groups together. Cluster analysis led to identification of three
      distinct groups when considering only the control group. For the diabetic group,
      and the computation considering both groups together, four distinct groups were
      isolated. Compared to the cluster analysis of the control group an additional
      forefoot loading pattern was identified. This group comprised diabetic feet only.
      The relevance of the reported clusters was supported by ANOVA statistics
      indicating significant differences between different regions of interest and
      different clusters. CONCLUSION/S SIGNIFICANCE: There seems to emerge a new era in
      diabetic foot medicine which embraces the classification of diabetic patients
      according to their biomechanical profile. Classification of the plantar pressure
      distribution has the potential to provide a means to determine mechanical
      interventions for the prevention and/or treatment of the diabetic foot.

PMID- 24278220
TI  - Enzymatic characterization of insecticide resistance mechanisms in field
      populations of Malaysian Culex quinquefasciatus say (Diptera: Culicidae).
AB  - BACKGROUND: There has been no comprehensive study on biochemical characterization
      of insecticide resistance mechanisms in field populations of Malaysian Culex
      quinquefasciatus. To fill this void in the literature, a nationwide investigation
      was performed to quantify the enzyme activities, thereby attempting to
      characterize the potential resistance mechanisms in Cx. quinquefasciatus in
      residential areas in Malaysia. METHODOLOGY/PRINCIPAL FINDINGS: Culex
      quinquefasciatus from 14 residential areas across 13 states and one federal
      territory were subjected to esterases, mixed function oxidases, glutathione-S
      transferase and insensitive acetylcholinesterase assays. Enzyme assays revealed
      that alpha-esterases and beta-esterases were elevated in 13 populations and 12
      populations, respectively. Nine populations demonstrated elevated levels of mixed
      function oxidases and glutathione-S-transferase. Acetylcholinesterase was
      insensitive to propoxur in all 14 populations. Activity of alpha-esterases
      associated with malathion resistance was found in the present study. In addition,
      an association between the activity of alpha-esterases and beta-esterases was
      also demonstrated. CONCLUSIONS/SIGNIFICANCE: The present study has characterized
      the potential biochemical mechanisms in contributing towards insecticide
      resistance in Cx. quinquefasciatus field populations in Malaysia. Identification
      of mechanisms underlying the insecticide resistance will be beneficial in
      developing effective mosquito control programs in Malaysia.

PMID- 24278221
TI  - Development of reference transcriptomes for the major field insect pests of
      cowpea: a toolbox for insect pest management approaches in west Africa.
AB  - Cowpea is a widely cultivated and major nutritional source of protein for many
      people that live in West Africa. Annual yields and longevity of grain storage is
      greatly reduced by feeding damage caused by a complex of insect pests that
      include the pod sucking bugs, Anoplocnemis curvipes Fabricius (Hemiptera:
      Coreidae) and Clavigralla tomentosicollis Stal (Hemiptera: Coreidae); as well as
      phloem-feeding cowpea aphids, Aphis craccivora Koch (Hemiptera: Aphididae) and
      flower thrips, Megalurothrips sjostedti Trybom (Thysanoptera: Thripidae). Efforts
      to control these pests remain a challenge and there is a need to understand the
      structure and movement of these pest populations in order to facilitate the
      development of integrated pest management strategies (IPM). Molecular tools have
      the potential to help facilitate a better understanding of pest populations.
      Towards this goal, we used 454 pyrosequencing technology to generate 319,126,
      176,262, 320,722 and 227,882 raw reads from A. curvipes, A. craccivora, C.
      tomentosicollis and M. sjostedti, respectively. The reads were de novo assembled
      into 11,687, 7,647, 10,652 and 7,348 transcripts for A. curvipes, A. craccivora,
      C. tomentosicollis and M. sjostedti, respectively. Functional annotation of the
      resulting transcripts identified genes putatively involved in insecticide
      resistance, pathogen defense and immunity. Additionally, sequences that matched
      the primary aphid endosymbiont, Buchnera aphidicola, were identified among A.
      craccivora transcripts. Furthermore, 742, 97, 607 and 180 single nucleotide
      polymorphisms (SNPs) were respectively predicted among A. curvipes, A.
      craccivora, C. tomentosicollis and M. sjostedti transcripts, and will likely be
      valuable tools for future molecular genetic marker development. These results
      demonstrate that Roche 454-based transcriptome sequencing could be useful for the
      development of genomic resources for cowpea pest insects in West Africa. 

PMID- 24278222
TI  - Photographic Atlas and three-dimensional reconstruction of the holotype skull of
      Euhelopus zdanskyi with description of additional cranial elements.
AB  - BACKGROUND: Euhelopus zdanskyi is one of relatively few sauropod taxa known from
      an almost complete skull and mandible. Recent phylogenetic analyses suggest that
      Euhelopus is a somphospondylan titanosauriform, and that it is a member of the
      clade (Euhelopodidae) which is the sister taxon to the hugely successful,
      dominantly Cretaceous sauropod group Titanosauria. METHODOLOGY/PRINCIPAL
      FINDINGS: The skull elements of Euhelopus were CT scanned at Uppsala Akademiska
      Sjukhuset. Three-dimensional models of the elements were constructed from the
      DICOM data using Mimics 14.0, InVesalius 3.0, and GeoMagic Studio 2012, the skull
      was rearticulated in Rhinoceros 4.0, and the final version was rendered in
      GeoMagic Studio 2012. CONCLUSIONS/SIGNIFICANCE: The fact that relatively complete
      sauropod skulls are so rare in the fossil record, particularly among
      titanosauriforms, means that the skulls that are known should be as thoroughly
      described and well-illustrated as possible. This contribution supplements
      previous descriptions of the cranial elements of Euhelopus, one of the few
      euhelopodid taxa for which cranial material is known, by presenting a
      comprehensive photographic atlas of the skull elements to facilitate a better
      understanding of their morphology. We describe several elements which have been
      overlooked in past studies of Euhelopus, and also provide as accurate a
      reconstruction of the skull as possible (in the absence of the braincase), the
      most significant components of which are the articulations of the palate and the
      mandible.

PMID- 24278224
TI  - RADtyping: an integrated package for accurate de novo codominant and dominant RAD
      genotyping in mapping populations.
AB  - Genetic linkage maps are indispensable tools in genetic, genomic and breeding
      studies. As one of genotyping-by-sequencing methods, RAD-Seq (restriction-site
      associated DNA sequencing) has gained particular popularity for construction of
      high-density linkage maps. Current RAD analytical tools are being predominantly
      used for typing codominant markers. However, no genotyping algorithm has been
      developed for dominant markers (resulting from recognition site disruption).
      Given their abundance in eukaryotic genomes, utilization of dominant markers
      would greatly diminish the extensive sequencing effort required for large-scale
      marker development. In this study, we established, for the first time, a novel
      statistical framework for de novo dominant genotyping in mapping populations. An
      integrated package called RADtyping was developed by incorporating both de novo
      codominant and dominant genotyping algorithms. We demonstrated the superb
      performance of RADtyping in achieving remarkably high genotyping accuracy based
      on simulated and real mapping datasets. The RADtyping package is freely available
      at http://www2.ouc.edu.cn/mollusk/ detailen.asp?id=727. 

PMID- 24278223
TI  - Specific serotonergic denervation affects tau pathology and cognition without
      altering senile plaques deposition in APP/PS1 mice.
AB  - Senile plaques and neurofibrillary tangles are major neuropathological features
      of Alzheimer's Disease (AD), however neuronal loss is the alteration that best
      correlates with cognitive impairment in AD patients. Underlying neurotoxic
      mechanisms are not completely understood although specific neurotransmission
      deficiencies have been observed in AD patients and, in animal models, cholinergic
      and noradrenergic denervation may increase amyloid-beta deposition and tau
      phosphorylation in denervated areas. On the other hand brainstem
      neurodegeneration has been suggested as an initial event in AD, and serotonergic
      dysfunction, as well as reductions in raphe neurones density, have been reported
      in AD patients. In this study we addressed whether specific serotonergic
      denervation, by administering 5,7-dihydroxitriptamine (5,7-DHT) in the raphe
      nuclei, could also worsen central pathology in APPswe/PS1dE9 mice or interfere
      with learning and memory activities. In our hands specific serotonergic
      denervation increased tau phosphorylation in denervated cortex, without affecting
      amyloid-beta (Abeta) pathology. We also observed that APPswe/PS1dE9 mice lesioned
      with 5,7-DHT were impaired in the Morris water maze test, supporting a
      synergistic effect of the serotonergic denervation and the presence of APP/PS1
      transgenes on learning and memory impairment. Altogether our data suggest that
      serotonergic denervation may interfere with some pathological aspects observed in
      AD, including tau phosphorylation or cognitive impairment, without affecting
      Abeta pathology, supporting a differential role of specific neurotransmitter
      systems in AD. 

PMID- 24278225
TI  - Nitrotyrosine level was associated with mortality in patients with acute kidney
      injury.
AB  - BACKGROUND: To examine the characteristics of oxidative stress in patients with
      acute kidney injury (AKI) and investigate the association between plasma
      nitrotyrosine levels and 90-day mortality in patients with AKI.
      METHODOLOGY/PRINCIPAL FINDINGS: 158 patients with hospital-acquired AKI were
      recruited to this prospective cohort study according to RIFLE (Risk, Injury,
      Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients
      without AKI and 15 age and gender-matched healthy subjects served as control.
      Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of
      patients with AKI. The patients with AKI were followed up for 90 days and grouped
      according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was
      detected in patients with AKI compared with healthy subjects, and critically ill
      patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with
      high 3-NT/Tyr showed significant differences compared with the curves of
      individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis
      (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated
      with mortality after adjustment for age, gender, sepsis and Acute Physiology and
      Chronic Health Evaluation (APACHE) II score. CONCLUSIONS/SIGNIFICANCE: There is
      excess plasma protein oxidation in patients with AKI, as evidenced by increased
      nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI
      patients independent of the severity of illness.

PMID- 24278226
TI  - Relative effects of road risk, habitat suitability, and connectivity on wildlife
      roadkills: the case of tawny owls (Strix aluco).
AB  - BACKGROUND: Despite its importance for reducing wildlife-vehicle collisions,
      there is still incomplete understanding of factors responsible for high road
      mortality. In particular, few empirical studies examined the idea that spatial
      variation in roadkills is influenced by a complex interplay between road-related
      factors, and species-specific habitat quality and landscape connectivity.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study we addressed this issue, using a 7
      year dataset of tawny owl (Strix aluco) roadkills recorded along 37 km of road in
      southern Portugal. We used a multi-species roadkill index as a surrogate of
      intrinsic road risk, and we used a Maxent distribution model to estimate habitat
      suitability. Landscape connectivity was estimated from least-cost paths between
      tawny owl territories, using habitat suitability as a resistance surface. We
      defined 10 alternative scenarios to compute connectivity, based on variation in
      potential movement patterns according to territory quality and dispersal distance
      thresholds. Hierarchical partitioning of a regression model indicated that
      independent variation in tawny owl roadkills was explained primarily by the
      roadkill index (70.5%) and, to a much lesser extent, by landscape connectivity
      (26.2%), while habitat suitability had minor effects (3.3%). Analysis of
      connectivity scenarios suggested that owl roadkills were primarily related to
      short range movements (<5 km) between high quality territories. Tawny owl
      roadkills were spatially autocorrelated, but the introduction of spatial filters
      in the regression model did not change the type and relative contribution of
      environmental variables. CONCLUSIONS: Overall, results suggest that road-related
      factors may have a dominant influence on roadkill patterns, particularly in areas
      like ours where habitat quality and landscape connectivity are globally high for
      the study species. Nevertheless, the study supported the view that functional
      connectivity should be incorporated whenever possible in roadkill models, as it
      may greatly increase their power to predict the location of roadkill hotspots.

PMID- 24278227
TI  - Impact of glucose-lowering agents on the risk of cancer in type 2 diabetic
      patients. The Barcelona case-control study.
AB  - BACKGROUND: The aim of the present study is to evaluate the impact of glucose
      lowering agents in the risk of cancer in a large type 2 diabetic population.
      METHODS: A nested case-control study was conducted within a defined cohort
      (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of
      Barcelona). Cases (n = 1,040) comprised those subjects with any cancer diagnosed
      between 2008 and 2010, registered at the Cancer Registry of Hospital Vall
      d'Hebron (Barcelona). Three control subjects for each case (n = 3,120) were
      matched by age, sex, diabetes duration, and geographical area. The treatments
      analyzed (within 3 years prior to cancer diagnosis) were: insulin glargine,
      insulin detemir, human insulin, fast-acting insulin and analogues, metformin,
      sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4
      inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions
      were used to calculate the risk of cancer associated with the use of each drug
      adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit,
      and diabetes duration. RESULTS: No differences were observed between case and
      control subjects for the proportion, dose or duration of exposure to each
      treatment. None of the types of insulin and oral agents analyzed showed a
      significant increase in the risk of cancer. Moreover, no cancer risk was observed
      when glargine was used alone or in combination with metformin. CONCLUSIONS: Our
      results suggest that diabetes treatment does not influence the risk of cancer
      associated with type 2 diabetes. Therefore, an eventual increase of cancer should
      not be a reason for biasing the selection of any glucose-lowering treatment in
      type 2 diabetic population.

PMID- 24278228
TI  - The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft
      rejection in mice: cholinergic pathway modulates alloreactivity.
AB  - Activation of innate immunity through Toll-like receptors (TLR) can abrogate
      transplantation tolerance by revealing hidden T cell alloreactivity. Separately,
      the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage
      activation and cytokine release during endotoxemia and ischemia reperfusion
      injury. However, the relevance of the alpha7 nicotinic acetylcholine receptor
      (alpha7nAChR)-dependent anti-inflammatory pathway in the process of allograft
      rejection or maintenance of tolerance remains unknown. The aim of our study is to
      investigate whether the cholinergic pathway could impact T cell alloreactivity
      and transplant outcome in mice. For this purpose, we performed minor-mismatched
      skin allografts using donor/recipient combinations genetically deficient for the
      alpha7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were
      housed in an environment with endogenous pathogen exposure or the graft was
      treated with direct application of imiquimod (a TLR7 ligand). The alpha7nAChR
      deficient recipient mice showed accelerated rejection compared to wild type
      recipient mice under these conditions of TLR activation. The accelerated
      rejection was associated with enhanced IL-17 and IFN-gamma production by
      alloreactive T cells. An alpha7nAChR-deficiency in the donor tissue facilitated
      allograft rejection but not in recipient mice. In addition, adoptive T cell
      transfer experiments in skin-grafted lymphopenic animals revealed a direct
      regulatory role for the alpha7nAChR on T cells. Taken together, our data
      demonstrate that the cholinergic pathway regulates alloreactivity and
      transplantation tolerance at multiple levels. One implication suggested by our
      work is that, in an organ transplant setting, deliberate alpha7nAChR stimulation
      of brain dead donors might be a valuable approach for preventing donor tissue
      inflammation prior to transplant. 

PMID- 24278229
TI  - Association between telomere length and type 2 diabetes mellitus: a meta
      analysis.
AB  - BACKGROUND: Several epidemiological studies have examined the association between
      shortened telomere length and type 2 diabetes mellitus (T2DM), while the results
      remained conflicting. We conducted a meta-analysis to derive a more precise
      estimation of the relationship between them. METHODS: We systematically reviewed
      the databases of PubMed, EMBASE, and Web of Science for all studies on the
      association between telomere length and T2DM. We conducted this study assessed by
      STATA 11.0. Data were summarized using random-effects or fixed-effects meta
      analysis. The heterogeneity and publication bias among studies were examined by
      using chi(2)-based Q statistic test and Egger's test, respectively. RESULTS: Nine
      cohorts consisting of 5759 cases and 6518 controls were selected into the meta
      analysis. The results indicated that shortened telomere length was significantly
      associated with T2DM risk (OR: 1.291; 95% CI: 1.112, 1.498; P<0.001) with
      heterogeneity (I(2) = 71.6%). When three cohorts responsible for the
      heterogeneity were excluded, the pooled OR for the remaining cohorts indicated a
      significant association between shortened telomere length and T2DM (OR: 1.117;
      95% CI: 1.002, 1.246; P = 0.045) without heterogeneity. CONCLUSION: We found a
      statistically significant association between shortened telomere length and T2DM.

PMID- 24278230
TI  - Plasma interferon-gamma-inducible protein-10 levels are associated with early,
      but not sustained virological response during treatment of acute or early chronic
      HCV infection.
AB  - BACKGROUND: High plasma levels of interferon-gamma inducible protein-10 (IP-10)
      have been shown to be associated with impaired treatment response in chronic
      hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in
      acute HCV infection is unknown. METHODS: Patients with acute or early chronic HCV
      infection from the Australian Trial in Acute Hepatitis C (ATAHC) cohort were
      evaluated. Baseline and on-treatment plasma IP-10 levels were measured by ELISA.
      IL28B genotype was determined by sequencing. RESULTS: Overall, 74 HCV mono
      infected and 35 HIV/HCV co-infected patients were treated in ATAHC, of whom 89
      were adherent to therapy and were included for analysis. IP-10 levels correlated
      with HCV RNA levels at baseline (r = 0.48, P<0.001) and during treatment.
      Baseline IP-10 levels were higher in patients who failed to achieve rapid
      virological response (RVR). Only one patient with a plasma IP-10 level >600 pg/mL
      achieved RVR. There was no association with IP-10 levels and early virological
      response (EVR) or sustained virological response (SVR). CONCLUSIONS: Baseline IP
      10 levels are associated with early viral kinetics but not ultimate treatment
      outcome in acute HCV infection. Given previous data showing that patients with
      high baseline IP-10 are unlikely to spontaneously clear acute HCV infection, they
      should be prioritized for early antiviral therapy.

PMID- 24278231
TI  - Salmon and human thrombin differentially regulate radicular pain, glial-induced
      inflammation and spinal neuronal excitability through protease-activated receptor
      1.
AB  - Chronic neck pain is a major problem with common causes including disc herniation
      and spondylosis that compress the spinal nerve roots. Cervical nerve root
      compression in the rat produces sustained behavioral hypersensitivity, due in
      part to the early upregulation of pro-inflammatory cytokines, the sustained
      hyperexcitability of neurons in the spinal cord and degeneration in the injured
      nerve root. Through its activation of the protease-activated receptor-1 (PAR1),
      mammalian thrombin can enhance pain and inflammation; yet at lower concentrations
      it is also capable of transiently attenuating pain which suggests that PAR1
      activation rate may affect pain maintenance. Interestingly, salmon-derived
      fibrin, which contains salmon thrombin, attenuates nerve root-induced pain and
      inflammation, but the mechanisms of action leading to its analgesia are unknown.
      This study evaluates the effects of salmon thrombin on nerve root-mediated pain,
      axonal degeneration in the root, spinal neuronal hyperexcitability and
      inflammation compared to its human counterpart in the context of their enzymatic
      capabilities towards coagulation substrates and PAR1. Salmon thrombin
      significantly reduces behavioral sensitivity, preserves neuronal myelination,
      reduces macrophage infiltration in the injured nerve root and significantly
      decreases spinal neuronal hyperexcitability after painful root compression in the
      rat; whereas human thrombin has no effect. Unlike salmon thrombin, human thrombin
      upregulates the transcription of IL-1beta and TNF-alpha and the secretion of IL-6
      by cortical cultures. Salmon and human thrombins cleave human fibrinogen-derived
      peptides and form clots with fibrinogen with similar enzymatic activities, but
      salmon thrombin retains a higher enzymatic activity towards coagulation
      substrates in the presence of antithrombin III and hirudin compared to human
      thrombin. Conversely, salmon thrombin activates a PAR1-derived peptide more
      weakly than human thrombin. These results are the first to demonstrate that
      salmon thrombin has unique analgesic, neuroprotective and anti-inflammatory
      capabilities compared to human thrombin and that PAR1 may contribute to these
      actions. 

PMID- 24278232
TI  - Correlation of chromosomal instability, telomere length and telomere maintenance
      in microsatellite stable rectal cancer: a molecular subclass of rectal cancer.
AB  - INTRODUCTION: Colorectal cancer (CRC) tumor DNA is characterized by chromosomal
      damage termed chromosomal instability (CIN) and excessively shortened telomeres.
      Up to 80% of CRC is microsatellite stable (MSS) and is historically considered to
      be chromosomally unstable (CIN+). However, tumor phenotyping depicts some MSS CRC
      with little or no genetic changes, thus being chromosomally stable (CIN-). MSS
      CIN- tumors have not been assessed for telomere attrition. EXPERIMENTAL DESIGN:
      MSS rectal cancers from patients <=50 years old with Stage II (B2 or higher) or
      Stage III disease were assessed for CIN, telomere length and telomere maintenance
      mechanism (telomerase activation [TA]; alternative lengthening of telomeres
      [ALT]). Relative telomere length was measured by qPCR in somatic epithelial and
      cancer DNA. TA was measured with the TRAPeze assay, and tumors were evaluated for
      the presence of C-circles indicative of ALT. p53 mutation status was assessed in
      all available samples. DNA copy number changes were evaluated with Spectral
      Genomics aCGH. RESULTS: Tumors were classified as chromosomally stable (CIN-) and
      chromosomally instable (CIN+) by degree of DNA copy number changes. CIN- tumors
      (35%; n=6) had fewer copy number changes (<17% of their clones with DNA copy
      number changes) than CIN+ tumors (65%; n=13) which had high levels of copy number
      changes in 20% to 49% of clones. Telomere lengths were longer in CIN- compared to
      CIN+ tumors (p=0.0066) and in those in which telomerase was not activated
      (p=0.004). Tumors exhibiting activation of telomerase had shorter tumor telomeres
      (p=0.0040); and tended to be CIN+ (p=0.0949). CONCLUSIONS: MSS rectal cancer
      appears to represent a heterogeneous group of tumors that may be categorized both
      on the basis of CIN status and telomere maintenance mechanism. MSS CIN- rectal
      cancers appear to have longer telomeres than those of MSS CIN+ rectal cancers and
      to utilize ALT rather than activation of telomerase.

PMID- 24278233
TI  - Scales of spatial heterogeneity of plastic marine debris in the northeast pacific
      ocean.
AB  - Plastic debris has been documented in many marine ecosystems, including remote
      coastlines, the water column, the deep sea, and subtropical gyres. The North
      Pacific Subtropical Gyre (NPSG), colloquially called the "Great Pacific Garbage
      Patch," has been an area of particular scientific and public concern. However,
      quantitative assessments of the extent and variability of plastic in the NPSG
      have been limited. Here, we quantify the distribution, abundance, and size of
      plastic in a subset of the eastern Pacific (approximately 20-40 degrees N, 120
      155 degrees W) over multiple spatial scales. Samples were collected in Summer
      2009 using surface and subsurface plankton net tows and quantitative visual
      observations, and Fall 2010 using surface net tows only. We documented
      widespread, though spatially variable, plastic pollution in this portion of the
      NPSG and adjacent waters. The overall median microplastic numerical concentration
      in Summer 2009 was 0.448 particles m(-2) and in Fall 2010 was 0.021 particles m(
      2), but plastic concentrations were highly variable over the submesoscale (10 s
      of km). Size-frequency spectra were skewed towards small particles, with the most
      abundant particles having a cross-sectional area of approximately 0.01 cm(2).
      Most microplastic was found on the sea surface, with the highest densities
      detected in low-wind conditions. The numerical majority of objects were small
      particles collected with nets, but the majority of debris surface area was found
      in large objects assessed visually. Our ability to detect high-plastic areas
      varied with methodology, as stations with substantial microplastic did not
      necessarily also contain large visually observable objects. A power analysis of
      our data suggests that high variability of surface microplastic will make future
      changes in abundance difficult to detect without substantial sampling effort. Our
      findings suggest that assessment and monitoring of oceanic plastic debris must
      account for high spatial variability, particularly in regards to the evaluation
      of initiatives designed to reduce marine debris. 

PMID- 24278234
TI  - Development and evaluation of a SYBR green-based real time RT-PCR assay for
      detection of the emerging avian influenza A (H7N9) virus.
AB  - Most recently a novel avian-origin influenza A (H7N9) virus emerged in China and
      has been associated with lots of human infection and fatal cases. Genetic
      analysis of the viral genome revealed that this reassortant virus might be better
      adapted to humans than other avian influenza viruses. Molecular diagnostic
      methods are thus urgently needed in public health laboratories. In this study, a
      SYBR green-based one-step real time reverse transcription-PCR (RT-PCR) was
      developed to detect the novel H7N9 virus. The primer pairs on the basis of the
      hemagglutinin and neuraminidase gene sequences of H7N9 viruses amplified subtype
      specific fragments with Tm values of 80.77+/-0.06 degrees C for H7 and 81.20+/
      0.17 degrees C for N9 respectively. The standard curves showed a dynamic linear
      range across 6 log units of RNA copy number (10(6) to 10(1) copies/ ul) with a
      detection limit of 10 copies per reaction for both H7 and N9 assays by using
      serial ten-fold diluted in-vitro transcribed viral RNA. In addition, no cross
      reactivity was observed with seasonal H1N1, H1N1 pdm09, H3N2, H5N1 and H9N2
      viruses as well as other human respiratory viruses. When the assay was further
      evaluated in H7N9 virus infected clinical samples, positive amplification signals
      were obtained in all of the specimens with the accordance between H7 and N9
      assays. Therefore, the established SYBR green-based real time RT-PCR assay could
      provide a rapid, sensitive, specific and reliable alternative approach with lower
      costs for high throughput screening of suspected samples from humans, animals and
      environments in first line public health laboratories. 

PMID- 24278235
TI  - Modulation of gene expression in contextual fear conditioning in the rat.
AB  - In contextual fear conditioning (CFC) a single training leads to long-term memory
      of context-aversive electrical foot-shocks association. Mid-temporal regions of
      the brain of trained and naive rats were obtained 2 days after conditioning and
      screened by two-directional suppression subtractive hybridization. A pool of
      differentially expressed genes was identified and some of them were randomly
      selected and confirmed with qRT-PCR assay. These transcripts showed high homology
      for rat gene sequences coding for proteins involved in different cellular
      processes. The expression of the selected transcripts was also tested in rats
      which had freely explored the experimental apparatus (exploration) and in rats to
      which the same number of aversive shocks had been administered in the same
      apparatus, but temporally compressed so as to make the association between
      painful stimuli and the apparatus difficult (shock-only). Some genes resulted
      differentially expressed only in the rats subjected to CFC, others only in
      exploration or shock-only rats, whereas the gene coding for translocase of outer
      mitochondrial membrane 20 protein and nardilysin were differentially expressed in
      both CFC and exploration rats. For example, the expression of stathmin 1 whose
      transcripts resulted up regulated was also tested to evaluate the transduction
      and protein localization after conditioning. 

PMID- 24278236
TI  - Serum CXCL9 levels are associated with tumor progression and treatment outcome in
      patients with nasopharyngeal carcinoma.
AB  - OBJECTIVES: The aim of this cohort study was to examine the role of the chemokine
      (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC). MATERIALS &
      METHODS: Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor
      samples were enrolled. CXCL9 expression in tissue samples was analyzed by
      quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations
      were measured by enzyme-linked immunosorbent assay. RESULTS: CXCL9 expression was
      significantly higher in tumors than in normal epithelium. CXCL9 serum
      concentrations were also significantly higher in NPC patients compared to those
      in healthy individuals (516.8+/-617.6 vs. 170.7+/-375.0 pg/mL, P<0.0001). Serum
      CXCL9 levels were significantly higher in NPC patients with higher tumor stages,
      nodal stages, and overall stages (P<0.001, P = 0.001, and P<0.001, respectively).
      We found a statistically significant correlation between the concentrations of
      CXCL9 and EBV DNA load in the NPC patients (Spearman's correlation analysis; r =
      0.473, P<0.001; 95% confidence interval, 0.346-0.582). Moreover, NPC patients
      with higher CXCL9 levels (>290 pg/mL, median) before treatment had worse
      prognoses for overall survival and disease-free survival (P = 0.045 and P =
      0.008, respectively). Multivariate logistic regression analyses also indicated
      that higher CXCL9 serum levels were an independent prognostic factor for disease
      free survival (P = 0.015). CONCLUSION: Our study demonstrated that CXCL9 is
      associated with tumor burden and aggressiveness of NPC tumors and the serum level
      of this ligand may be useful as a prognostic indicator.

PMID- 24278237
TI  - Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2
      null mutant mice.
AB  - The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal
      development. During postnatal growth, MSX2 is expressed in all cells involved in
      mineralized tissue formation and plays a role in their differentiation and
      function. Msx2 null (Msx2 (-/-)) mice display complex craniofacial skeleton
      abnormalities with bone and tooth defects. A moderate form osteopetrotic
      phenotype is observed, along with decreased expression of RANKL (TNFSF11), the
      main osteoclast-differentiating factor. In order to elucidate the role of such an
      osteopetrosis in the Msx2 (-/-) mouse dental phenotype, a bone resorption rescue
      was performed by mating Msx2 (-/-) mice with a transgenic mouse line
      overexpressing Rank (Tnfrsf11a). Msx2 (-/-) Rank(Tg) mice had significant
      improvement in the molar phenotype, while incisor epithelium defects were
      exacerbated in the enamel area, with formation of massive osteolytic tumors.
      Although compensation for RANKL loss of function could have potential as a
      therapy for osteopetrosis, but in Msx2 (-/-) mice, this approach via RANK
      overexpression in monocyte-derived lineages, amplified latent epithelial tumor
      development in the peculiar continuously growing incisor. 

PMID- 24278238
TI  - Urinary triclosan is associated with elevated body mass index in NHANES.
AB  - BACKGROUND: Triclosan-a ubiquitous chemical in toothpastes, soaps, and household
      cleaning supplies-has the potential to alter both gut microbiota and endocrine
      function and thereby affect body weight. METHODS: We investigated the
      relationship between triclosan and body mass index (BMI) using National Health
      and Nutrition Examination Surveys (NHANES) from 2003-2008. BMI and spot urinary
      triclosan levels were obtained from adults. Using two different exposure measures
      either presence vs. absence or quartiles of triclosan-we assessed the association
      between triclosan and BMI. We also screened all NHANES serum and urine biomarkers
      to identify correlated factors that might confound observed associations.
      RESULTS: Compared with undetectable triclosan, a detectable level was associated
      with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to
      the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were
      associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p =
      0.33) respectively. The one strong correlate of triclosan identified in NHANES
      was its metabolite, 2,4-dichlorophenol (rho = 0.4); its association with BMI,
      however, was weaker than that of triclosan. No other likely confounder was
      identified. CONCLUSIONS: Triclosan exposure is associated with increased BMI.
      Stronger effect at moderate than high levels suggests a complex mechanism of
      action.

PMID- 24278240
TI  - Profound effects of population density on fitness-related traits in an invasive
      freshwater snail.
AB  - Population density can profoundly influence fitness-related traits and population
      dynamics, and density dependence plays a key role in many prominent ecological
      and evolutionary hypotheses. Here, we evaluated how individual-level changes in
      population density affect growth rate and embryo production early in reproductive
      maturity in two different asexual lineages of Potamopyrgus antipodarum, a New
      Zealand freshwater snail that is an important model system for ecotoxicology and
      the evolution of sexual reproduction as well as a potentially destructive
      worldwide invader. We showed that population density had a major influence on
      individual growth rate and early-maturity embryo production, effects that were
      often apparent even when comparing treatments that differed in population density
      by only one individual. While individual growth rate generally decreased as
      population density increased, we detected a hump-shaped relationship between
      embryo production and density, with females from intermediate-density treatments
      producing the most embryos and females from low- and high-density treatments
      producing the fewest embryos. The two lineages responded similarly to the
      treatments, indicating that these effects of population density might apply more
      broadly across P. antipodarum. These results indicate that there are profound and
      complex relationships between population density, growth rate, and early-maturity
      embryo production in at least two lineages of this important model system, with
      potential implications for the study of invasive populations, research on the
      maintenance of sex, and approaches used in ecotoxicology. 

PMID- 24278239
TI  - Functional reorganization of motor and limbic circuits after exercise training in
      a rat model of bilateral parkinsonism.
AB  - Exercise training is widely used for neurorehabilitation of Parkinson's disease
      (PD). However, little is known about the functional reorganization of the injured
      brain after long-term aerobic exercise. We examined the effects of 4 weeks of
      forced running wheel exercise in a rat model of dopaminergic deafferentation
      (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training,
      cerebral perfusion was mapped during treadmill walking or at rest using [(14)C]
      iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue
      radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by
      statistical parametric mapping. In non-exercised rats, lesions resulted in
      persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed
      altered functional brain activation during walking, including: 1. hypoactivation
      of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the
      basal ganglia-thalamocortical circuit; 3. functional recruitment of the red
      nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the
      ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment
      of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas
      (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings
      show remarkable similarities to imaging findings reported in PD patients.
      Exercise progressively improved motor deficits in lesioned rats, while increasing
      activation in dorsal striatum and rostral secondary motor cortex, attenuating a
      hyperemia of the zona incerta and eliciting a functional reorganization of
      regions participating in the cerebellar-thalamocortical circuit. Both lesions and
      exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral
      striatum, laterodorsal tegmental n., ventral pallidum), as well as in related
      paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted
      in decreases in rCBF in the medial prefrontal cortex (cingulate, prelimbic,
      infralimbic). Our results in this PD rat model uniquely highlight the breadth of
      functional reorganizations in motor and limbic circuits following lesion and long
      term, aerobic exercise, and provide a framework for understanding the neural
      substrates underlying exercise-based neurorehabilitation. 

PMID- 24278241
TI  - Association between the CYP4A11 T8590C variant and essential hypertension: new
      data from Han Chinese and a meta-analysis.
AB  - OBJECTIVE: CYP4A11 oxidizes endogenous arachidonic acid to 20
      hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic in humans.
      Previous studies demonstrated an association between a functional variant
      (T8590C) of CYP4A11 and essential hypertension, though with conflicting results.
      To elucidate this relationship, a case-control study and meta-analysis were
      performed to assess the possible association of essential hypertension with
      CYP4A11 genetic variations. METHODS: Associations between the T8590C polymorphism
      and essential hypertension were examined in 328 unrelated cases and 297 age
      matched controls in Han Chinese individuals. High-resolution melting was used to
      identify the CYP4A11 variant. To further investigate the association, we
      conducted a meta-analysis including eight studies published previously in July
      2012. RESULTS: The frequency of the CYP4A11 T8590C polymorphism showed no
      significant difference between cases and controls (all P>0.05). However, the meta
      analysis showed that the CYP4A11 T8590C polymorphism may increase the risk of
      essential hypertension in an additive model (OR: 1.15, 95% CI: 1.02-1.29, P =
      0.02), a dominant model (OR: 1.06, 95% CI: 1.01-1.32, P = 0.03), a recessive
      model (OR: 1.52, 95% CI: 1.15-2.02, P = 0.003) and a homozygote contrast (OR:
      1.38, 95% CI: 1.07-1.78, P = 0.01). Also, a significant relationship was observed
      among Caucasians in the additive model, the homozygote contrast, the recessive
      model and the dominant model (all P<0.05). However, no association was observed
      in an Asian population (all P>0.05). CONCLUSIONS: This meta-analysis suggests
      there is a significant association between the CYP4A11 T8590C variant and
      essential hypertension, especially in Caucasians. The case-control study did not
      find a significant association among the Han Chinese population, but the controls
      were poorly matched and meaningful conclusions cannot therefore be made. Further
      large-scale studies are needed to clarify whether the CYP4A11 T8590C polymorphism
      is associated with hypertension risk in Asians or has a gender-specific effect.

PMID- 24278242
TI  - Persistence of hepatitis C virus during and after otherwise clinically successful
      treatment of chronic hepatitis C with standard pegylated interferon alpha-2b and
      ribavirin therapy.
AB  - Resolution of chronic hepatitis C is considered when serum HCV RNA becomes
      repeatedly undetectable and liver enzymes normalize. However, long-term
      persistence of HCV following therapy with pegylated interferon-alpha/ribavirin
      (PegIFN/R) was reported when more sensitive assays and testing of serial plasma,
      lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess
      plasma and PBMCs collected during and after standard PegIFN/R therapy from
      individuals who became HCV RNA nonreactive by clinical testing. Of particular
      interest was to determine if HCV genome and its replication remain detectable
      during ongoing treatment with PegIFN/R when evaluated by more sensitive detection
      approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12-88
      weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them
      were reanalyzed for HCV RNA with sensitivity <2 IU/mL. Clone sequencing of the
      HCV 5'-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA
      was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8
      of 9 patients during therapy, although only 5.4% plasma samples were positive by
      clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20
      (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident
      replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive
      strand collected during or after treatment. Pre-treatment point mutations
      persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV
      is not completely cleared during ongoing administration of PegIFN/R otherwise
      capable of ceasing progression of CHC and virus commonly persists at levels not
      detectable by the current clinical testing. The findings suggest the need for
      continued evaluation even after patients achieve undetectable HCV RNA post
      treatment. 

PMID- 24278243
TI  - Estimation of unsteady aerodynamics in the wake of a freely flying European
      starling (Sturnus vulgaris).
AB  - Wing flapping is one of the most widespread propulsion methods found in nature;
      however, the current understanding of the aerodynamics in bird wakes is
      incomplete. The role of the unsteady motion in the flow and its contribution to
      the aerodynamics is still an open question. In the current study, the wake of a
      freely flying European starling has been investigated using long-duration high
      speed Particle Image Velocimetry (PIV) in the near wake. Kinematic analysis of
      the wings and body of the bird has been performed using additional high-speed
      cameras that recorded the bird movement simultaneously with the PIV measurements.
      The wake evolution of four complete wingbeats has been characterized through
      reconstruction of the time-resolved data, and the aerodynamics in the wake have
      been analyzed in terms of the streamwise forces acting on the bird. The profile
      drag from classical aerodynamics was found to be positive during most of the
      wingbeat cycle, yet kinematic images show that the bird does not decelerate. It
      is shown that unsteady aerodynamics are necessary to satisfy the drag/thrust
      balance by approximating the unsteady drag term. These findings may shed light on
      the flight efficiency of birds by providing a partial answer to how they minimize
      drag during flapping flight. 

PMID- 24278244
TI  - Snakebite and its socio-economic impact on the rural population of Tamil Nadu,
      India.
AB  - BACKGROUND: Snakebite represents a significant health issue worldwide, affecting
      several million people each year with as many as 95,000 deaths. India is
      considered to be the country most affected, but much remains unknown about
      snakebite incidence in this country, its socio-economic impact and how snakebite
      management could be improved. METHODS/PRINCIPAL FINDINGS: We conducted a study
      within rural villages in Tamil Nadu, India, which combines a household survey
      (28,494 people) of snakebite incidence with a more detailed survey of victims in
      order to understand the health and socio-economic effects of the bite, the
      treatments obtained and their views about future improvements. Our survey
      suggests that snakebite incidence is higher than previously reported. 3.9% of
      those surveyed had suffered from snakebite and the number of deaths corresponds
      to 0.45% of the population. The socio-economic impact of this is very
      considerable in terms of the treatment costs and the long-term effects on the
      health and ability of survivors to work. To reduce this, the victims recommended
      improvements to the accessibility and affordability of antivenom treatment.
      CONCLUSIONS: Snakebite has a considerable and disproportionate impact on rural
      populations, particularly in South Asia. This study provides an incentive for
      researchers and the public to work together to reduce the incidence and improve
      the outcomes for snake bite victims and their families.

PMID- 24278245
TI  - Long-term unemployment is associated with short telomeres in 31-year-old men: an
      observational study in the northern Finland birth cohort 1966.
AB  - OBJECTIVE: Life stress resulting from early-life experiences and domestic stress
      is linked with shorter leukocyte telomere length (LTL), but evidence on
      employment-related stress is scarce. We explored whether unemployment in early
      adulthood is associated with shorter LTL, a potential biomarker of premature
      aging. METHODS: We used data from 5620 men and women belonging to the Northern
      Finland Birth Cohort 1966. Individually registered unemployment days in 1995-97
      were compared with data on biological, behavioral and socioeconomic health
      predictors and existing medical conditions obtained by surveys and clinical
      examinations at follow-up in 1997-98. Mean LTL at follow-up was measured by
      multiplex quantitative real-time PCR. We calculated odds ratios and their 95%
      confidence intervals (CI) of belonging to the sex-stratified shortest decile of
      standardized relative mean LTL according to the categories of: 0, <260, <500 and
      over 500 unemployment days, representing 0, <1, <2 and over 2 calendar years.
      RESULTS: Among men, unemployment exceeding 500 days during three years was
      associated with having shorter LTL at follow-up, compared to being continuously
      employed. The corresponding odds ratio was 2.61 (95% CI 1.16 to 5.85) in the
      fully adjusted model. Such an association was not found among women in this
      study. CONCLUSIONS: Long-term unemployment in early adulthood is associated with
      shorter LTL among men.

PMID- 24278246
TI  - Harnessing gene conversion in chicken B cells to create a human antibody sequence
      repertoire.
AB  - Transgenic chickens expressing human sequence antibodies would be a powerful tool
      to access human targets and epitopes that have been intractable in mammalian
      hosts because of tolerance to conserved proteins. To foster the development of
      the chicken platform, it is beneficial to validate transgene constructs using a
      rapid, cell culture-based method prior to generating fully transgenic birds. We
      describe a method for the expression of human immunoglobulin variable regions in
      the chicken DT40 B cell line and the further diversification of these genes by
      gene conversion. Chicken VL and VH loci were knocked out in DT40 cells and
      replaced with human VK and VH genes. To achieve gene conversion of human genes in
      chicken B cells, synthetic human pseudogene arrays were inserted upstream of the
      functional human VK and VH regions. Proper expression of chimeric IgM comprised
      of human variable regions and chicken constant regions is shown. Most
      importantly, sequencing of DT40 genetic variants confirmed that the human
      pseudogene arrays contributed to the generation of diversity through gene
      conversion at both the Igl and Igh loci. These data show that engineered
      pseudogene arrays produce a diverse pool of human antibody sequences in chicken B
      cells, and suggest that these constructs will express a functional repertoire of
      chimeric antibodies in transgenic chickens. 

PMID- 24278247
TI  - The brain's response to the human voice depends on the incidence of autistic
      traits in the general population.
AB  - Optimal brain sensitivity to the fundamental frequency (F0) contour changes in
      the human voice is important for understanding a speaker's intonation, and
      consequently, the speaker's attitude. However, whether sensitivity in the brain's
      response to a human voice F0 contour change varies with an interaction between an
      individual's traits (i.e., autistic traits) and a human voice element (i.e.,
      presence or absence of communicative action such as calling) has not been
      investigated. In the present study, we investigated the neural processes involved
      in the perception of F0 contour changes in the Japanese monosyllables "ne" and
      "nu." "Ne" is an interjection that means "hi" or "hey" in English; pronunciation
      of "ne" with a high falling F0 contour is used when the speaker wants to attract
      a listener's attention (i.e., social intonation). Meanwhile, the Japanese
      concrete noun "nu" has no communicative meaning. We applied an adaptive spatial
      filtering method to the neuromagnetic time course recorded by whole-head
      magnetoencephalography (MEG) and estimated the spatiotemporal frequency dynamics
      of event-related cerebral oscillatory changes in beta band during the oddball
      paradigm. During the perception of the F0 contour change when "ne" was presented,
      there was event-related de-synchronization (ERD) in the right temporal lobe. In
      contrast, during the perception of the F0 contour change when "nu" was presented,
      ERD occurred in the left temporal lobe and in the bilateral occipital lobes. ERD
      that occurred during the social stimulus "ne" in the right hemisphere was
      significantly correlated with a greater number of autistic traits measured
      according to the Autism Spectrum Quotient (AQ), suggesting that the differences
      in human voice processing are associated with higher autistic traits, even in non
      clinical subjects. 

PMID- 24278248
TI  - Predicting drug-target interactions using drug-drug interactions.
AB  - Computational methods for predicting drug-target interactions have become
      important in drug research because they can help to reduce the time, cost, and
      failure rates for developing new drugs. Recently, with the accumulation of drug
      related data sets related to drug side effects and pharmacological data, it has
      became possible to predict potential drug-target interactions. In this study, we
      focus on drug-drug interactions (DDI), their adverse effects ([Formula: see
      text]) and pharmacological information ([Formula: see text]), and investigate the
      relationship among chemical structures, side effects, and DDIs from several data
      sources. In this study, [Formula: see text] data from the STITCH database,
      [Formula: see text] from drugs.com, and drug-target pairs from ChEMBL and SIDER
      were first collected. Then, by applying two machine learning approaches, a
      support vector machine (SVM) and a kernel-based L1-norm regularized logistic
      regression (KL1LR), we showed that DDI is a promising feature in predicting drug
      target interactions. Next, the accuracies of predicting drug-target interactions
      using DDI were compared to those obtained using the chemical structure and side
      effects based on the SVM and KL1LR approaches, showing that DDI was the data
      source contributing the most for predicting drug-target interactions. 

PMID- 24278249
TI  - Amyloidosis, synucleinopathy, and prion encephalopathy in a neuropathic lysosomal
      storage disease: the CNS-biomarker potential of peripheral blood.
AB  - Mucopolysaccharidosis (MPS) IIIB is a devastating neuropathic lysosomal storage
      disease with complex pathology. This study identifies molecular signatures in
      peripheral blood that may be relevant to MPS IIIB pathogenesis using a mouse
      model. Genome-wide gene expression microarrays on pooled RNAs showed
      dysregulation of 2,802 transcripts in blood from MPS IIIB mice, reflecting
      pathological complexity of MPS IIIB, encompassing virtually all previously
      reported and as yet unexplored disease aspects. Importantly, many of the
      dysregulated genes are reported to be tissue-specific. Further analyses of
      multiple genes linked to major pathways of neurodegeneration demonstrated a
      strong brain-blood correlation in amyloidosis and synucleinopathy in MPS IIIB. We
      also detected prion protein (Prnp) deposition in the CNS and Prnp dysregulation
      in the blood in MPS IIIB mice, suggesting the involvement of Prnp aggregation in
      neuropathology. Systemic delivery of trans-BBB-neurotropic rAAV9-hNAGLU vector
      mediated not only efficient restoration of functional alpha-N
      acetylglucosaminidase and clearance of lysosomal storage pathology in the central
      nervous system (CNS) and periphery, but also the correction of impaired
      neurodegenerative molecular pathways in the brain and blood. Our data suggest
      that molecular changes in blood may reflect pathological status in the CNS and
      provide a useful tool for identifying potential CNS-specific biomarkers for MPS
      IIIB and possibly other neurological diseases. 

PMID- 24278250
TI  - High environmental ozone levels lead to enhanced allergenicity of birch pollen.
AB  - BACKGROUND: Evidence is compelling for a positive correlation between climate
      change, urbanisation and prevalence of allergic sensitisation and diseases. The
      reason for this association is not clear to date. Some data point to a pro
      allergenic effect of anthropogenic factors on susceptible individuals.
      OBJECTIVES: To evaluate the impact of urbanisation and climate change on pollen
      allergenicity. METHODS: Catkins were sampled from birch trees from different
      sites across the greater area of Munich, pollen were isolated and an urbanisation
      index, NO2 and ozone exposure were determined. To estimate pollen allergenicity,
      allergen content and pollen-associated lipid mediators were measured in aqueous
      pollen extracts. Immune stimulatory and modulatory capacity of pollen was
      assessed by neutrophil migration assays and the potential of pollen to inhibit
      dendritic cell interleukin-12 response. In vivo allergenicity was assessed by
      skin prick tests. RESULTS: The study revealed ozone as a prominent environmental
      factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as
      assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond
      that, ozone induced changes in lipid composition and chemotactic and immune
      modulatory potential of the pollen. Higher ozone-exposed pollen was characterised
      by less immune modulatory but higher immune stimulatory potential. CONCLUSION: It
      is likely that future climate change along with increasing urbanisation will lead
      to rising ozone concentrations in the next decades. Our study indicates that
      ozone is a crucial factor leading to clinically relevant enhanced allergenicity
      of birch pollen. Thus, with increasing temperatures and increasing ozone levels,
      also symptoms of pollen allergic patients may increase further.

PMID- 24278251
TI  - Activation of olfactory receptors on mouse pulmonary macrophages promotes
      monocyte chemotactic protein-1 production.
AB  - BACKGROUND: Emerging evidence suggests that non-olfactory tissues and cells can
      express olfactory receptors (ORs), however, the exact function of ectopic OR
      expression remains unknown. We have previously shown in mouse models that a
      unique cooperation between interferon-gamma (IFN-gamma) and lipopolysaccharide
      (LPS) drives the activation of pulmonary macrophages and leads to the induction
      of pathogenic responses in the respiratory tract. Further, through gene array
      studies, we have shown that activation of macrophages by these molecules results
      in the selective expression of a number of ORs. In this study, we validated the
      expression of these ORs in mouse airway and pulmonary macrophages in response to
      IFN-gamma and LPS (gamma/LPS) stimulation, and further explored the effect of
      odorant stimulation on macrophage function. METHODOLOGY/PRINCIPAL FINDINGS: OR
      expression in airway and pulmonary macrophages in response to IFN-gamma, LPS or
      gamma/LPS treatments was assessed by microarray and validated by q-PCR. OR
      expression (e.g. OR622) on macrophages was confirmed by visualization in
      immunofluoresence assays. Functional responses to odorants were assessed by
      quantifying inflammatory cytokine and chemokine expression using q-PCR and cell
      migration was assessed by a modified Boyden chamber migration assay. Our results
      demonstrate that eight ORs are expressed at basal levels in both airway and
      pulmonary macrophages, and that gamma/LPS stimulation cooperatively increased
      this expression. Pulmonary macrophages exposed to the combined treatment of
      gamma/LPS+octanal (an odorant) exhibited a 3-fold increase in MCP-1 protein
      production, compared to cells treated with gamma/LPS alone. Supernatants from
      gamma/LPS+octanal exposed macrophages also increased macrophage migration in
      vitro. CONCLUSIONS/SIGNIFICANCE: Eight different ORs are expressed at basal
      levels in pulmonary macrophages and expression is upregulated by the synergistic
      action of gamma/LPS. Octanal stimulation further increased MCP-1 production and
      the motility of macrophages. Our results suggest that ORs may mediate macrophage
      function by regulating MCP-1 production and cell migration.

PMID- 24278252
TI  - miRNA signatures in sera of patients with active pulmonary tuberculosis.
AB  - Several studies showed that assessing levels of specific circulating microRNAs
      (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or
      detecting alterations in physiological conditions. We aimed to identify a serum
      miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for
      variations due to the genetic makeup, we enrolled adults from two study settings
      in Europe and Africa. The following categories of subjects were considered:
      healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected
      (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and
      active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were
      pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low
      density arrays. After identification of "relevant miRNAs", we refined the serum
      miRNA signature discriminating between H and PTB on individual subjects.
      Signatures were analyzed for their diagnostic performances using a multivariate
      logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross
      validation (LOOCV) approach was adopted for assessing how both models could
      perform in practice. The analysis on pooled specimens identified selected miRNAs
      as discriminatory for the categories analyzed. On individual serum samples, we
      showed that 15 miRNAs serve as signature for H and PTB categories with a
      diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a
      logistic classification model, respectively. Considering the different ethnicity,
      by selecting the specific signature for the European group (10 miRNAs) the
      diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3),
      respectively. The African-specific signature (12 miRNAs) increased the diagnostic
      accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum
      miRNA signatures represent an interesting source of biomarkers for TB disease
      with the potential to discriminate between PTB and LTBI, but also among the other
      categories. 

PMID- 24278254
TI  - PD5: a general purpose library for primer design software.
AB  - BACKGROUND: Complex PCR applications for large genome-scale projects require
      fast, reliable and often highly sophisticated primer design software
      applications. Presently, such applications use pipelining methods to utilise many
      third party applications and this involves file parsing, interfacing and data
      conversion, which is slow and prone to error. A fully integrated suite of
      software tools for primer design would considerably improve the development time,
      the processing speed, and the reliability of bespoke primer design software
      applications. RESULTS: The PD5 software library is an open-source collection of
      classes and utilities, providing a complete collection of software building
      blocks for primer design and analysis. It is written in object-oriented C(++)
      with an emphasis on classes suitable for efficient and rapid development of
      bespoke primer design programs. The modular design of the software library
      simplifies the development of specific applications and also integration with
      existing third party software where necessary. We demonstrate several
      applications created using this software library that have already proved to be
      effective, but we view the project as a dynamic environment for building primer
      design software and it is open for future development by the bioinformatics
      community. Therefore, the PD5 software library is published under the terms of
      the GNU General Public License, which guarantee access to source-code and allow
      redistribution and modification. CONCLUSIONS: The PD5 software library is
      downloadable from Google Code and the accompanying Wiki includes instructions and
      examples: http://code.google.com/p/primer-design.

PMID- 24278253
TI  - Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine
      protease cathepsin L-Like rCPB2.8.
AB  - BACKGROUND: Cysteine protease B is considered crucial for the survival and
      infectivity of the Leishmania in its human host. Several microorganism pathogens
      bind to the heparin-like glycosaminoglycans chains of proteoglycans at host-cell
      surface to promote their attachment and internalization. Here, we have
      investigated the influence of heparin upon Leishmania mexicana cysteine protease
      rCPB2.8 activity. METHODOLOGY/PRINCIPAL FINDINGS: THE DATA ANALYSIS REVEALED THAT
      THE PRESENCE OF HEPARIN AFFECTS ALL STEPS OF THE ENZYME REACTION: (i) it
      decreases 3.5-fold the k 1 and 4.0-fold the k -1, (ii) it affects the acyl-enzyme
      accumulation with pronounced decrease in k 2 (2.7-fold), and also decrease in k 3
      (3.5-fold). The large values of DeltaG  =  12 kJ/mol for the association and
      dissociation steps indicate substantial structural strains linked to the
      formation/dissociation of the ES complex in the presence of heparin, which
      underscore a conformational change that prevents the diffusion of substrate in
      the rCPB2.8 active site. Binding to heparin also significantly decreases the
      alpha-helix content of the rCPB2.8 and perturbs the intrinsic fluorescence
      emission of the enzyme. The data strongly suggest that heparin is altering the
      ionization of catalytic (Cys(25))-S(-)/(His(163))-Im(+) H ion pair of the
      rCPB2.8. Moreover, the interaction of heparin with the N-terminal pro-region of
      rCPB2.8 significantly decreased its inhibitory activity against the mature
      enzyme. CONCLUSIONS/SIGNIFICANCE: Taken together, depending on their
      concentration, heparin-like glycosaminoglycans can either stimulate or antagonize
      the activity of cysteine protease B enzymes during parasite infection, suggesting
      that this glycoconjugate can anchor parasite cysteine protease at host cell
      surface.

PMID- 24278255
TI  - Darwin's Duchenne: eye constriction during infant joy and distress.
AB  - Darwin proposed that smiles with eye constriction (Duchenne smiles) index strong
      positive emotion in infants, while cry-faces with eye constriction index strong
      negative emotion. Research has supported Darwin's proposal with respect to
      smiling, but there has been little parallel research on cry-faces (open-mouth
      expressions with lateral lip stretching). To investigate the possibility that eye
      constriction indexes the affective intensity of positive and negative emotions,
      we first conducted the Face-to-Face/Still-Face (FFSF) procedure at 6 months. In
      the FFSF, three minutes of naturalistic infant-parent play interaction (which
      elicits more smiles than cry-faces) are followed by two minutes in which the
      parent holds an unresponsive still-face (which elicits more cry-faces than
      smiles). Consistent with Darwin's proposal, eye constriction was associated with
      stronger smiling and with stronger cry-faces. In addition, the proportion of
      smiles with eye constriction was higher during the positive-emotion eliciting
      play episode than during the still-face. In parallel, the proportion of cry-faces
      with eye constriction was higher during the negative-emotion eliciting still-face
      than during play. These results are consonant with the hypothesis that eye
      constriction indexes the affective intensity of both positive and negative facial
      configurations. A preponderance of eye constriction during cry-faces was observed
      in a second elicitor of intense negative emotion, vaccination injections, at both
      6 and 12 months of age. The results support the existence of a Duchenne distress
      expression that parallels the more well-known Duchenne smile. This suggests that
      eye constriction-the Duchenne marker-has a systematic association with early
      facial expressions of intense negative and positive emotion. 

PMID- 24278256
TI  - 4q22.1 contributes to bone mineral density and osteoporosis susceptibility in
      postmenopausal women of Chinese Han population.
AB  - Osteoporosis is a multifactorial disease in which genetic determinants are
      modulated by hormonal, environmental and nutritional factors. An important
      clinical risk factor in the pathogenesis of osteoporosis is the presence of
      genetics polymorphism in/around susceptibility genes/regions. This study explored
      whether the region of 4q22.1, which confers risk of developing osteoporosis in
      some populations, associated with bone mineral density and osteoporosis
      susceptibility in postmenopausal women of Han Chinese. We investigated 32 SNPs
      with minor allele frequencies >=0.05 between 20 kb upstream and 20 kb downstream
      (40 kb window) of rs6532023, mapping in the 4q22.1 region, which was reported to
      be significantly associated with osteoporosis in previous studies. We found that
      rs6532023 was significantly associated with bone mineral density and osteoporosis
      (corrected p = 0.015) in our sample, including 440 cases and 640 controls, and
      allele G was supposed as a risk factor while T worked as a protective factor.
      Further genotype association analyses suggested a similar pattern (corrected p =
      0.040). Additionally, analyses by haplotypes indicated that a haplotype block
      rs7683315-rs6532023-rs1471400-rs1471403 in the region associated with bone
      mineral density and osteoporosis (global p = 0.032), and risk haplotype A-G-G-C
      had almost 1.5-fold increased in the cases. To our knowledge, this is the first
      report to examine 4q22.1 region polymorphisms and osteoporosis in Han Chinese.
      Our results provide further evidence for an effect of the region of 4q22.1 on the
      etiology of osteoporosis and suggest that 4q22.1 may be a genetic risk factor for
      bone mineral density and osteoporosis. 

PMID- 24278257
TI  - The role of pH fronts in tissue electroporation based treatments.
AB  - Treatments based on electroporation (EP) induce the formation of pores in cell
      membranes due to the application of pulsed electric fields. We present
      experimental evidence of the existence of pH fronts emerging from both electrodes
      during treatments based on tissue EP, for conditions found in many studies, and
      that these fronts are immediate and substantial. pH fronts are indirectly
      measured through the evanescence time (ET), defined as the time required for the
      tissue buffer to neutralize them. The ET was measured through a pH indicator
      imaged at a series of time intervals using a four-cluster hard fuzzy-c-means
      algorithm to segment pixels corresponding to the pH indicator at every frame. The
      ET was calculated as the time during which the number of pixels was 10% of those
      in the initial frame. While in EP-based treatments such as reversible (ECT) and
      irreversible electroporation (IRE) the ET is very short (though enough to cause
      minor injuries) due to electric pulse characteristics and biological buffers
      present in the tissue, in gene electrotransfer (GET), ET is much longer, enough
      to denaturate plasmids and produce cell damage. When any of the electric pulse
      parameters is doubled or tripled the ET grows and, remarkably, when any of the
      pulse parameters in GET is halved, the ET drops significantly. Reducing pH fronts
      has relevant implications for GET treatment efficiency, due to a substantial
      reduction of plasmid damage and cell loss. 

PMID- 24278258
TI  - Prevalence and predictors of disability 24-months after injury for hospitalised
      and non-hospitalised participants: results from a longitudinal cohort study in
      New Zealand.
AB  - INTRODUCTION: Most studies investigating disability outcomes following injury
      have examined hospitalised patients. It is not known whether variables associated
      with disability outcomes are similar for injured people who are not hospitalised.
      AIMS: This paper compares the prevalence of disability 24 months after injury for
      participants in the Prospective Outcomes of Injury Study who were hospitalised
      and those non-hospitalised, and also seeks to identify pre-injury and injury
      related predictors of disability among hospitalised and non-hospitalised
      participants. METHODS: Participants, aged 18-64 years, were recruited from an
      injury claims register managed by New Zealand's no-fault injury compensation
      insurer after referral by health care professionals. A wide range of pre-injury
      socio-demographic, health and psychosocial characteristics were collected, as
      well as injury-related characteristics; outcome is assessed using the WHODAS.
      Multivariable models estimating relative risks of disability for hospitalised and
      non-hospitalised participants were developed using Poisson regression methods.
      RESULTS: Of 2856 participants, analyses were restricted to 2184 (76%)
      participants for whom both pre-injury and 24 month WHODAS data were available. Of
      these, 25% were hospitalised. In both hospitalised and non-hospitalised groups,
      13% experience disability (WHODAS>=10) 24 months after injury; higher than pre
      injury (5%). Of 28 predictor variables, seven independently placed injured
      participants in the hospitalised group at increased risk of disability 24 months
      after injury; eight in the non-hospitalised. Only four predictors (pre-injury
      disability, two or more pre-injury chronic conditions, pre-injury BMI>=30 and
      trouble accessing healthcare services) were common to both the hospitalised and
      non-hospitalised groups. There is some evidence to suggest that among the
      hospitalised group, Maori have higher risk of disability relative to non-Maori.
      CONCLUSIONS: At 24 months considerable disability is borne, equally, by
      hospitalised and non-hospitalised groups. However, predictors of disability are
      not necessarily consistent between the hospitalised and non-hospitalised groups,
      suggesting caution in generalising results from one group to the other.

PMID- 24278259
TI  - Repetitive transcranial magnetic stimulation attenuates the perception of force
      output production in non-exercised hand muscles after unilateral exercise.
AB  - We examined whether unilateral exercise creates perception bias in the non
      exercised limb and ascertained whether rTMS applied to the primary motor cortex
      (M1) interferes with this perception. All participants completed 4 interventions:
      1) 15-min learning period of intermittent isometric contractions at 35% MVC with
      the trained hand (EX), 2) 15-min learning period of intermittent isometric
      contractions at 35% MVC with the trained hand whilst receiving rTMS over the
      contralateral M1 (rTMS+EX); 3) 15-min of rTMS over the 'trained' M1 (rTMS) and 4)
      15-min rest (Rest). Pre and post-interventions, the error of force output
      production, the perception of effort (RPE), motor evoked potentials (MEPs) and
      compound muscle action potentials (CMAPs) were measured in both hands. EX did not
      alter the error of force output production in the trained hand (Delta3%; P>0.05);
      however, the error of force output production was reduced in the untrained hand
      (Delta12%; P<0.05). rTMS+EX and rTMS alone did not show an attenuation in the
      error of force output production in either hand. EX increased RPE in the trained
      hand (9.1+/-0.5 vs. 11.3+/-0.7; P<0.01) but not the untrained hand (8.8+/-0.6 vs.
      9.2+/-0.6; P>0.05). RPE was significantly higher after rTMS+EX in the trained
      hand (9.2+/-0.5 vs. 10.7+/-0.7; P<0.01) but ratings were unchanged in the
      untrained hand (8.5+/-0.6 vs. 9.2+/-0.5; P>0.05). The novel finding was that
      exercise alone reduced the error in force output production by over a third in
      the untrained hand. Further, when exercise was combined with rTMS the transfer of
      force perception was attenuated. These data suggest that the contralateral M1 of
      the trained hand might, in part, play an essential role for the transfer of force
      perception to the untrained hand. 

PMID- 24278260
TI  - Intratumoral hepatic stellate cells as a poor prognostic marker and a new
      treatment target for hepatocellular carcinoma.
AB  - Hepatic stellate cells (HSCs), a specialized stromal cytotype in the liver, have
      been demonstrated to actively contribute to hepatocellular carcinoma (HCC)
      development. However, the previous studies were performed using HSC cell lines,
      and the prognostic value of intratumoral HSCs (tHSCs) was unclear. Here we
      isolated tHSCs from fresh human HCC tissues, and analyzed the abilities of tHSCs
      to promote HCC progression by using in vitro assays for cell viability, migration
      and invasion as well as epithelial-mesenchymal transition (EMT) phenotype. 252
      HCC patients who underwent hepatectomy were enrolled for analysis of tHSCs and E
      cadherin expression in tumor tissues, and 55 HCC patients for analysis of tHSCs
      in tumor tissues and circulating tumor cells (CTCs) in blood. Prognostic factors
      were then identified. The results showed that coculture of tHSCs with HCC cells
      had a stronger effect on HCC cell viability, migration and invasion, accompanied
      with the acquisition of epithelial-mesenchymal transition (EMT) phenotype. In
      vivo cotransplantation of HCC cells with tHSCs into nude mice more efficiently
      promoted tumor formation and growth. Icaritin, a known apoptosis inducer of HSCs,
      was demonstrated to effectively inhibit tHSC proliferation in vitro and tHSC
      induced HCC-promoting effects in vivo. Clinical evidence indicated that tHSCs
      were rich in 45% of the HCC specimens, tHSC-rich subtypes were negatively
      correlated either with E-cadherin expression in tumor tissues (r = -0.256, p <
      0.001) or with preoperative CTCs in blood (r = -0.287, p = 0.033), and were
      significantly correlated with tumor size (p = 0.027), TNM staging (p = 0.018),
      and vascular invasion (p = 0.008). Overall and recurrence-free survival rates of
      tHSC-rich patients were significantly worse than those for tHSC-poor patients.
      Multivariate analysis revealed tHSC-rich as an independent factor for overall and
      recurrence-free survival. In conclusion, tHSCs provide a promising prognostic
      biomarker and a new treatment target for HCC. 

PMID- 24278261
TI  - Evaluation of circulating proteins and hemodynamics towards predicting mortality
      in children with pulmonary arterial hypertension.
AB  - BACKGROUND: Although many predictors have been evaluated, a set of strong
      independent prognostic mortality indicators has not been established in children
      with pediatric pulmonary arterial hypertension (PAH). The aim of this study was
      to identify a combination of clinical and molecular predictors of survival in
      PAH. METHODS: This single-center, retrospective cohort study was performed from
      children with PAH between 2001 and 2008 at Children's Hospital Colorado. Blood
      samples from 83 patients (median age of 8.3 years-old) were obtained. We
      retrospectively analyzed 46 variables, which included 27 circulating proteins, 7
      demographic variables and 12 hemodynamic and echocardiographic variables for
      establishing the best predictors of mortality. A data mining approach was
      utilized to evaluate predictor variables and to uncover complex data structures
      while performing variable selection in high dimensional problems. RESULTS:
      Thirteen children (16%) died during follow-up (median; 3.1 years) and survival
      rates from time of sample collection at 1 year, 3 years and 5 years were 95%, 85%
      and 79%, respectively. A subset of potentially informative predictors were
      identified, the top four are listed here in order of importance: Tissue
      inhibitors of metalloproteinases-1 (TIMP-1), apolipoprotein-AI, RV/LV diastolic
      dimension ratio and age at diagnosis. In univariate analysis, TIMP-1 and
      apolipoprotein-AI had significant association with survival time (hazard ratio
      [95% confidence interval]: 1.25 [1.03, 1.51] and 0.70 [0.54-0.90], respectively).
      Patients grouped by TIMP-1 and apolipoprotein-AI values had significantly
      different survival risks (p<0.01). CONCLUSION: Important predictors of mortality
      were identified from a large number of circulating proteins and clinical markers
      in this cohort. If confirmed in other populations, measurement of a subset of
      these predictors could aid in management of pediatric PAH by identifying patients
      at risk for death. These findings also further support a role for the clinical
      utility of measuring circulating proteins.

PMID- 24278262
TI  - Discovery of genes related to witches broom disease in Paulownia tomentosa *
      Paulownia fortunei by a De Novo assembled transcriptome.
AB  - In spite of its economic importance, very little molecular genetics and genomic
      research has been targeted at the family Paulownia spp. The little genetic
      information on this plant is a big obstacle to studying the mechanisms of its
      ability to resist Paulownia Witches' Broom (PaWB) disease. Analysis of the
      Paulownia transcriptome and its expression profile data are essential to
      extending the genetic resources on this species, thus will greatly improves our
      studies on Paulownia. In the current study, we performed the de novo assembly of
      a transcriptome on P. tomentosa * P. fortunei using the short-read sequencing
      technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was
      obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete
      structures were chosen. Eukaryotic clusters of orthologous groups, gene
      orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were
      performed of these unigenes. Genes related to PaWB disease resistance were
      analyzed in detail. To our knowledge, this is the first study to elucidate the
      genetic makeup of Paulownia. This transcriptome provides a quick way to
      understanding Paulownia, increases the number of gene sequences available for
      further functional genomics studies and provides clues to the identification of
      potential PaWB disease resistance genes. This study has provided a comprehensive
      insight into gene expression profiles at different states, which facilitates the
      study of each gene's roles in the developmental process and in PaWB disease
      resistance. 

PMID- 24278263
TI  - Residential selection across the life course: adolescent contextual and
      individual determinants of neighborhood disadvantage in mid-adulthood.
AB  - BACKGROUND: Numerous cross-sectional studies have examined neighborhood effects
      on health. Residential selection in adulthood has been stressed as an important
      cause of selection bias but has received little empirical attention, particularly
      its determinants from the earlier life course. The present study aims to examine
      whether neighborhood, family, school, health behaviors and health in adolescence
      are related to socioeconomic disadvantage of one's neighborhood of residence in
      adulthood. METHODS: Based on the prospective Northern Swedish Cohort (analytical
      N = 971, 90.6% retention rate), information was collected at age 16 years
      concerning family circumstances, school adjustment, health behaviors and mental
      and physical health. Neighborhood register data was linked to the cohort and used
      to operationalize aggregated measures of neighborhood disadvantage (ND) at age 16
      and 42. Data was analyzed with linear mixed models, with ND in adulthood
      regressed on adolescent predictors and neighborhood of residence in adolescence
      as the level-2 unit. RESULTS: Neighborhood disadvantage in adulthood was
      clustered by neighborhood of residence in adolescence (ICC = 8.6%). The
      clustering was completely explained by ND in adolescence. Of the adolescent
      predictors, ND (b = .14 (95% credible interval = .07-.22)), final school marks (b
      = -.18 (-.26--.10)), socioeconomic disadvantage (b = .07 (.01-.14)), and, with
      borderline significance, school peer problems (b = .07 (-.00-.13)), were
      independently related to adulthood ND in the final adjusted model. In sex
      stratified analyses, the most important predictors were school marks (b = -.21 (
      .32--.09)) in women, and neighborhood of residence (ICC = 15.5%) and ND (b = .20
      (.09-.31)) in men. CONCLUSIONS: These findings show that factors from adolescence
      - which also may impact on adult health - could influence the neighborhood
      context in which one will live in adulthood. This indicates that residential
      selection bias in neighborhood effects on health research may have its sources in
      early life.

PMID- 24278264
TI  - Semi-automatic quantification of subsolid pulmonary nodules: comparison with
      manual measurements.
AB  - RATIONALE: Accurate measurement of subsolid pulmonary nodules (SSN) is becoming
      increasingly important in the management of these nodules. SSNs were previously
      quantified with time-consuming manual measurements. The aim of the present study
      is to test the feasibility of semi-automatic SSNs measurements and to compare the
      results to the manual measurements. METHODS: In 33 lung cancer screening
      participants with 33 SSNs, the nodules were previously quantified by two
      observers manually. In the present study two observers quantified these nodules
      by using semi-automated nodule volumetry software. Nodules were quantified for
      effective diameter, volume and mass. The manual and semi-automatic measurements
      were compared using Bland-Altman plots and paired T tests. Observer agreement was
      calculated as an intraclass correlation coefficient. Data are presented as mean
      (SD). RESULTS: Semi-automated measurements were feasible in all 33 nodules.
      Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311)
      milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344)
      milligrams for observer 2, respectively. Agreement between observers and within
      observer 1 for the semi-automatic measurements was good with an intraclass
      correlation coefficient >0.89. For observer 1 and observer 2, measured diameter
      was 8.8% and 10.3% larger (p<0.001), measured volume was 24.3% and 26.5% larger
      (p<0.001) and measured mass was 10.6% and 12.0% larger (p<0.001) with the semi
      automatic program compared to the manual measurements. CONCLUSION: Semi-automated
      measurement of the diameter, volume and mass of SSNs is feasible with good
      observer agreement. Semi-automated measurement makes quantification of mass and
      volume feasible in daily practice.

PMID- 24278265
TI  - Imaging findings of primary splenic lymphoma: a review of 17 cases in which
      diagnosis was made at splenectomy.
AB  - PURPOSE: This study sought to characterize the imaging features of primary
      splenic lymphoma (PSL). MATERIALS AND METHODS: Pathological and imaging data from
      17 patients with primary splenic lymphoma initially diagnosed at splenectomy were
      retrospectively analyzed. Pretreatment computed tomography (CT) imaging was
      available for 16 patients, and magnetic resonance imaging (MRI) data were
      available for 4 patients. Splenic lymphoma imaging data were categorized based on
      the gross pathological presentation in the following manner: type 1, homogeneous
      enlargement; type 2, miliary nodules; type 3, multifocal masses of varying size;
      and type 4, solitary large mass. RESULTS: Of the 17 patients with PSL, 16 cases
      were non-Hodgkin lymphoma, and of these, 9 cases were diffuse large B cell
      lymphomas (DLBCL) and 4 cases were splenic marginal zone B-cell lymphoma (SMZL).
      Imaging showed the following types of PSL presentation: 1 case of type 1, 0 cases
      of type 2, 4 cases of type 3, and 12 cases of type 4. There was evidence of
      necrosis in 12 cases (70.6%), and there was evidence of mild enhancement in
      enhanced CT in 14 cases and in enhanced MRI in 3 cases. Prior to surgery, PSL was
      considered possible in 8 patients. CONCLUSION: The most frequent histological
      subtype was DLBCL, followed by SMZL. In both CT and MRI, PSL generally presents
      as a solitary mass or masses rather than as splenomegaly. In addition, necrosis
      and mild enhancement are commonly observed, and splenectomy may be required to
      confirm the diagnosis.

PMID- 24278266
TI  - Effective cerebral connectivity during silent speech reading revealed by
      functional magnetic resonance imaging.
AB  - Seeing the articulatory gestures of the speaker ("speech reading") enhances
      speech perception especially in noisy conditions. Recent neuroimaging studies
      tentatively suggest that speech reading activates speech motor system, which then
      influences superior-posterior temporal lobe auditory areas via an efference copy.
      Here, nineteen healthy volunteers were presented with silent videoclips of a
      person articulating Finnish vowels /a/, /i/ (non-targets), and /o/ (targets)
      during event-related functional magnetic resonance imaging (fMRI). Speech reading
      significantly activated visual cortex, posterior fusiform gyrus (pFG), posterior
      superior temporal gyrus and sulcus (pSTG/S), and the speech motor areas,
      including premotor cortex, parts of the inferior (IFG) and middle (MFG) frontal
      gyri extending into frontal polar (FP) structures, somatosensory areas, and
      supramarginal gyrus (SMG). Structural equation modelling (SEM) of these data
      suggested that information flows first from extrastriate visual cortex to pFS,
      and from there, in parallel, to pSTG/S and MFG/FP. From pSTG/S information flow
      continues to IFG or SMG and eventually somatosensory areas. Feedback connectivity
      was estimated to run from MFG/FP to IFG, and pSTG/S. The direct functional
      connection from pFG to MFG/FP and feedback connection from MFG/FP to pSTG/S and
      IFG support the hypothesis of prefrontal speech motor areas influencing auditory
      speech processing in pSTG/S via an efference copy. 

PMID- 24278267
TI  - Rapid diagnosis of diarrhea caused by Shigella sonnei using dipsticks; comparison
      of rectal swabs, direct stool and stool culture.
AB  - BACKGROUND: We evaluated a dipstick test for rapid detection of Shigella sonnei
      on bacterial colonies, directly on stools and from rectal swabs because in actual
      field situations, most pathologic specimens for diagnosis correspond to stool
      samples or rectal swabs. METHODOLOGY/PRINCIPAL FINDINGS: The test is based on the
      detection of S. sonnei lipopolysaccharide (LPS) O-side chains using phase I
      specific monoclonal antibodies coupled to gold particles, and displayed on a one
      step immunochromatographic dipstick. A concentration as low as 5 ng/ml of LPS was
      detected in distilled water and in reconstituted stools in 6 minutes. This is the
      optimal time for lecture to avoid errors of interpretation. In distilled water
      and in reconstituted stools, an unequivocal positive reaction was obtained with 4
      x 10(6) CFU/ml of S. sonnei. The specificity was 100% when tested with a battery
      of Shigella and different unrelated strains. When tested on 342 rectal swabs in
      Chile, specificity (281/295) was 95.3% (95% CI: 92.9% - 97.7%) and sensitivity
      (47/47) was 100%. Stool cultures and the immunochromatographic test showed
      concordant results in 95.5 % of cases (328/342) in comparative studies. Positive
      and negative predictive values were 77% (95% CI: 65% - 86.5%) and 100%
      respectively. When tested on 219 stools in Chile, Vietnam, India and France,
      specificity (190/198) was 96% (95% CI 92%-98%) and sensitivity (21/21) was 100%.
      Stool cultures and the immunochromatographic test showed concordant results in
      96.3 % of cases (211/219) in comparative studies. Positive and negative
      predictive values were 72.4% (95% CI 56.1%-88.6%) and 100 %, respectively.
      CONCLUSION: This one-step dipstick test performed well for diagnosis of S. sonnei
      both on stools and on rectal swabs. These data confirm a preliminary study done
      in Chile.

PMID- 24278268
TI  - Non-invasive in vivo imaging of near infrared-labeled transferrin in breast
      cancer cells and tumors using fluorescence lifetime FRET.
AB  - The conjugation of anti-cancer drugs to endogenous ligands has proven to be an
      effective strategy to enhance their pharmacological selectivity and delivery
      towards neoplasic tissues. Since cell proliferation has a strong requirement for
      iron, cancer cells express high levels of transferrin receptors (TfnR), making
      its ligand, transferrin (Tfn), of great interest as a delivery agent for
      therapeutics. However, a critical gap exists in the ability to non-invasively
      determine whether drugs conjugated to Tfn are internalized into target cells in
      vivo. Due to the enhanced permeability and retention (EPR) effect, it remains
      unknown whether these Tfn-conjugated drugs are specifically internalized into
      cancer cells or are localized non-specifically as a result of a generalized
      accumulation of macromolecules near tumors. By exploiting the dimeric nature of
      the TfnR that binds two molecules of Tfn in close proximity, we utilized a
      Forster Resonance Energy Transfer (FRET) based technique that can discriminate
      bound and internalized Tfn from free, soluble Tfn. In order to non-invasively
      visualize intracellular amounts of Tfn in tumors through live animal tissues, we
      developed a novel near infrared (NIR) fluorescence lifetime FRET imaging
      technique that uses an active wide-field time gated illumination platform. In
      summary, we report that the NIR fluorescence lifetime FRET technique is capable
      of non-invasively detecting bound and internalized forms of Tfn in cancer cells
      and tumors within a live small animal model, and that our results are
      quantitatively consistent when compared to well-established intensity-based FRET
      microscopy methods used in in vitro experiments. 

PMID- 24278269
TI  - A physical map of the short arm of wheat chromosome 1A.
AB  - Bread wheat (Triticum aestivum) has a large and highly repetitive genome which
      poses major technical challenges for its study. To aid map-based cloning and
      future genome sequencing projects, we constructed a BAC-based physical map of the
      short arm of wheat chromosome 1A (1AS). From the assembly of 25,918 high
      information content (HICF) fingerprints from a 1AS-specific BAC library, 715
      physical contigs were produced that cover almost 99% of the estimated size of the
      chromosome arm. The 3,414 BAC clones constituting the minimum tiling path were
      end-sequenced. Using a gene microarray containing ~40 K NCBI UniGene EST
      clusters, PCR marker screening and BAC end sequences, we arranged 160 physical
      contigs (97 Mb or 35.3% of the chromosome arm) in a virtual order based on
      synteny with Brachypodium, rice and sorghum. BAC end sequences and information
      from microarray hybridisation was used to anchor 3.8 Mbp of Illumina sequences
      from flow-sorted chromosome 1AS to BAC contigs. Comparison of genetic and synteny
      based physical maps indicated that ~50% of all genetic recombination is confined
      to 14% of the physical length of the chromosome arm in the distal region. The 1AS
      physical map provides a framework for future genetic mapping projects as well as
      the basis for complete sequencing of chromosome arm 1AS. 

PMID- 24278270
TI  - Activation of auditory cortex by anticipating and hearing emotional sounds: an
      MEG study.
AB  - To study how auditory cortical processing is affected by anticipating and hearing
      of long emotional sounds, we recorded auditory evoked magnetic fields with a
      whole-scalp MEG device from 15 healthy adults who were listening to emotional or
      neutral sounds. Pleasant, unpleasant, or neutral sounds, each lasting for 6 s,
      were played in a random order, preceded by 100-ms cue tones (0.5, 1, or 2 kHz) 2
      s before the onset of the sound. The cue tones, indicating the valence of the
      upcoming emotional sounds, evoked typical transient N100m responses in the
      auditory cortex. During the rest of the anticipation period (until the beginning
      of the emotional sound), auditory cortices of both hemispheres generated slow
      shifts of the same polarity as N100m. During anticipation, the relative strengths
      of the auditory-cortex signals depended on the upcoming sound: towards the end of
      the anticipation period the activity became stronger when the subject was
      anticipating emotional rather than neutral sounds. During the actual emotional
      and neutral sounds, sustained fields were predominant in the left hemisphere for
      all sounds. The measured DC MEG signals during both anticipation and hearing of
      emotional sounds implied that following the cue that indicates the valence of the
      upcoming sound, the auditory-cortex activity is modulated by the upcoming sound
      category during the anticipation period. 

PMID- 24278271
TI  - Close correlation between season of birth and the prevalence of bronchial asthma
      in a Taiwanese population.
AB  - BACKGROUND: Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis
      (AR) are common allergic diseases. Environmental factors were indicated to
      influence the development of allergic diseases. OBJECTIVE: To evaluate the
      correlation between the month of birth and the prevalence of allergic diseases in
      Taiwan. METHODS: Data from 104,455 children were collected from the National
      Insurance Research Database of Taiwan. Subjects were identified by at least two
      service claims for ambulatory care or one claim for inpatient care. All of the
      enrolled patients were aged 7~15 years in 2010. In a bio-clinical data analysis,
      total immunoglobulin E (IgE) and ImmunoCAPTM allergen data (CAP) from mothers and
      infants were collected in a medical center in Taiwan. Correlations between
      children's allergic factors and the season of birth were assessed. RESULTS: A
      significant difference in the prevalence of BA according to the month of birth
      (Chi(2) = 18.2, p<0.001) was found in the Taiwanese population. The fewest
      schoolchildren with were born in May (7.21%), and the most were born in October
      (10.59%). However, no tendency for the prevalence of AD (Chi(2) = 4.6, P = 0.204)
      or AR (Chi(2) = 4.3 P = 0.229) was found. In addition, we found that children
      born in autumn (August to October) had a higher prevalence of BA compared to
      those born in spring (February to April) (odds ratio: 1.13; 95% confidence
      interval: 1.05~1.21). In a bio-clinical data study, markers of maternal and
      childhood allergies including IgE and CAP were detected in a risk analysis
      section. Children who were born in autumn had higher levels of CAP and total IgE.
      CONCLUSIONS: The findings of this study showed that the month of birth was
      closely correlated with the prevalence of BA and higher levels of CAP and IgE.

PMID- 24278272
TI  - Diversification of fungal specific class a glutathione transferases in
      saprotrophic fungi.
AB  - Glutathione transferases (GSTs) form a superfamily of multifunctional proteins
      with essential roles in cellular detoxification processes and endogenous
      metabolism. The distribution of fungal-specific class A GSTs was investigated in
      saprotrophic fungi revealing a recent diversification within this class.
      Biochemical characterization of eight GSTFuA isoforms from Phanerochaete
      chrysosporium and Coprinus cinereus demonstrated functional diversity in
      saprotrophic fungi. The three-dimensional structures of three P. chrysosporium
      isoforms feature structural differences explaining the functional diversity of
      these enzymes. Competition experiments between fluorescent probes, and various
      molecules, showed that these GSTs function as ligandins with various small
      aromatic compounds, derived from lignin degradation or not, at a L-site
      overlapping the glutathione binding pocket. By combining genomic data with
      structural and biochemical determinations, we propose that this class of GST has
      evolved in response to environmental constraints induced by wood chemistry. 

PMID- 24278273
TI  - Functional digestive symptoms and quality of life in patients with Ehlers-Danlos
      syndromes: results of a national cohort study on 134 patients.
AB  - BACKGROUND AND OBJECTIVES: Ehlers-Danlos syndromes (EDS) are a heterogeneous
      group of heritable connective tissue disorders. Gastrointestinal manifestations
      in EDS have been described but their frequency, nature and impact are poorly
      known. We aimed to assess digestive features in a national cohort of EDS
      patients. METHODS: A questionnaire has been sent to 212 EDS patients through the
      French patient support group, all of which had been formally diagnosed according
      to the Villefranche criteria. The questionnaire included questions about
      digestive functional symptoms, the GIQLI (Gastrointestinal Quality of Life
      Index), KESS scoring system and the Rome III criteria. RESULTS: Overall, 135
      patients (64% response rate) completed the questionnaire and 134 were analyzable
      (123 women; 91%). Mean age and Body Mass Index were respectively 35+/-14.7 years
      and 24.3+/-6.1 kg/m(2). The most common EDS subtype was hypermobility form
      (n=108; 80.6%). GIQLI and KESS median values were respectively 63.5 (27-117) and
      19 [13.5-22]. Eighty four percent of patients had functional bowel disorders
      (FBD) according to the Rome III criteria. An irritable bowel syndrome according
      to the same criteria was observed in 64 patients (48%) and 48 patients (36%)
      reported functional constipation. A gastro-esophageal reflux disease (GERD) was
      reported in 90 patients (68.7%), significantly associated with a poorer GIQLI
      (60.5+/-16.8 versus 75.9+/-20.3; p<0.0001). GIQLI was also negatively impacted by
      the presence of an irritable bowel syndrome or functional constipation (p=0.007).
      There was a significant correlation between FBD and GERD. CONCLUSIONS: Natural
      frequency of gastrointestinal manifestations in EDS seems higher than previously
      assessed. FBD and GERD are very common in our study population, the largest ever
      published until now. Their impact is herein shown to be important. A systematic
      clinical assessment of digestive features should be recommended in EDS.

PMID- 24278274
TI  - Performance of polygenic scores for predicting phobic anxiety.
AB  - CONTEXT: Anxiety disorders are common, with a lifetime prevalence of 20% in the
      U.S., and are responsible for substantial burdens of disability, missed work days
      and health care utilization. To date, no causal genetic variants have been
      identified for anxiety, anxiety disorders, or related traits. OBJECTIVE: To
      investigate whether a phobic anxiety symptom score was associated with 3
      alternative polygenic risk scores, derived from external genome-wide association
      studies of anxiety, an internally estimated agnostic polygenic score, or
      previously identified candidate genes. DESIGN: Longitudinal follow-up study.
      Using linear and logistic regression we investigated whether phobic anxiety was
      associated with polygenic risk scores derived from internal, leave-one out genome
      wide association studies, from 31 candidate genes, and from out-of-sample genome
      wide association weights previously shown to predict depression and anxiety in
      another cohort. SETTING AND PARTICIPANTS: Study participants (n = 11,127) were
      individuals from the Nurses' Health Study and Health Professionals Follow-up
      Study. MAIN OUTCOME MEASURE: Anxiety symptoms were assessed via the 8-item phobic
      anxiety scale of the Crown Crisp Index at two time points, from which a
      continuous phenotype score was derived. RESULTS: We found no genome-wide
      significant associations with phobic anxiety. Phobic anxiety was also not
      associated with a polygenic risk score derived from the genome-wide association
      study beta weights using liberal p-value thresholds; with a previously published
      genome-wide polygenic score; or with a candidate gene risk score based on 31
      genes previously hypothesized to predict anxiety. CONCLUSION: There is a
      substantial gap between twin-study heritability estimates of anxiety disorders
      ranging between 20-40% and heritability explained by genome-wide association
      results. New approaches such as improved genome imputations, application of gene
      expression and biological pathways information, and incorporating social or
      environmental modifiers of genetic risks may be necessary to identify significant
      genetic predictors of anxiety.

PMID- 24278275
TI  - TLR4-MyD88/Mal-NF-kB axis is involved in infection of HSV-2 in human cervical
      epithelial cells.
AB  - We have established an in vitro HSV-2 acute infection model with Human cervical
      epithelial (HCE cells, the primary target and natural host cells for HSV-2) to
      investigate the role of TLRs-mediated innate immune response to HSV-2. In current
      study, we found that HSV-2 infection induced activity of NF-kB reporter and
      expression of cytokines are TLR4-dependent using approaches with shRNA and TLR4
      antagonist. Knockdown experiments demonstrated that the adaptor molecules MyD88
      and Mal of the TLRs signaling pathway are required in the HSV-2 induced TLR4
      dependent NF-kB activation in HCE cells. Western blot assay suggested that
      knockdown of TLR4 decreased the phosphorylation of IRAK1 and inhibitor of NF-kB
      (IkB-alpha) upon HSV-2 infection. Finally, decreased expression of either TLR4 or
      MyD88/Mal alone or both significantly abolished productions of IL-6 and IFN-beta
      by ELISA analysis. Taken together, our results from the in vitro infection model
      reveal for the first time that there exists the pathway via TLR4-Mal/MyD88-IRAK1
      NF-kB axis in human cervical epithelial cells in response to HSV-2 infection. 

PMID- 24278276
TI  - FoxO3a modulates hypoxia stress induced oxidative stress and apoptosis in cardiac
      microvascular endothelial cells.
AB  - Cardiac microvascular endothelial cells (CMECs) dysfunction induced by hypoxia is
      an important pathophysiological event in myocardium ischemic injury, whereas, the
      underlying mechanism is not fully clarified. FoxO transcription factors regulate
      target genes involved in apoptosis and cellular reactive oxygen species (ROS)
      production. Therefore, the present study was designed to elucidate the potential
      role of FoxOs on the hypoxia-induced ROS formation and apoptosis in CMECs.
      Exposure to low oxygen tension stimulated ROS accumulation and increased
      apoptosis in CMECs within 6-24 h. Hypoxia also significantly increased the
      expressions of HIF-1alpha and FoxO3a. However, hypoxia decreased the
      phosphorylation of Akt and FoxO3a, correlated with increased nuclear
      accumulation. Conversely, the expression of FoxO1 was not significantly altered
      by hypoxia. After inhibition of HIF-1alpha by siRNA, we observed that hypoxia
      induced ROS accumulation and apoptosis of CMECs were decreased. Meanwhile,
      knockdown of HIF-1alpha also inhibited hypoxia induced FoxO3a expression in
      CMECs, but did not affect FoxO1 expression. Furthermore, hypoxia-induced ROS
      formation and apoptosis in CMECs were correlated with the disturbance of Bcl-2
      family proteins, which were abolished by FoxO3a silencing with siRNA. In
      conclusion, our data provide evidence that FoxO3a leads to ROS accumulation in
      CMECs, and in parallel, induces the disturbance of Bcl-2 family proteins which
      results in apoptosis.

PMID- 24278277
TI  - Are frontal cognitive and atrophy patterns different in PSP and bvFTD? A
      comparative neuropsychological and VBM study.
AB  - Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD)
      are two clinicohistological entities that share a severe prefrontal syndrome. To
      what extent do the cognitive syndrome and the location of the underlying brain
      atrophy unify or segregate these entities? Here, we examined the clinical and
      radiological patterns of frontal involvement and the neural bases of the
      cognitive dysfunctions observed in the Richardson form of PSP and the behavioral
      variant of FTD (bvFTD). The cognitive profile and grey and white matter volume of
      PSP (n = 19) and bvFTD (n = 16) patients and control participants (n = 18) were
      compared using a standard battery of neuropsychological tests and voxel-based
      morphometry (VBM), respectively. Analyses of correlations between
      neuropsychological and morphometric data were additionally performed. The
      severity and qualitative pattern of cognitive dysfunction was globally similar
      between the two patient groups. Grey matter volume was decreased in widespread
      frontal areas and in the temporal uncus in bvFTD, while it was decreased in the
      frontal and temporal lobes as well as in the thalamus in PSP. We also found an
      unexpected involvement of the frontal rectal gyrus in PSP patients compared to
      controls. Correlation analyses yielded different results in the two groups, with
      no area showing significant correlations in PSP patients, while several frontal
      and some temporal areas did so in bvFTD patients. In spite of minor
      neuropsychological and morphological differences, this study shows that the
      patterns of cognitive dysfunction and atrophy are very similar in PSP and bvFTD.
      However, executive dysfunction in these diseases may stem from partially
      divergent cortical and subcortical neural circuits. 

PMID- 24278278
TI  - Identification of a low digestibility delta-Conglutin in yellow lupin (Lupinus
      luteus L.) seed meal for atlantic salmon (Salmo salar L.) by coupling 2D-PAGE and
      mass spectrometry.
AB  - The need of quality protein in the aquaculture sector has forced the
      incorporation of alternative plant proteins into feeding diets. However, most
      plant proteins show lower digestibility levels than fish meal proteins,
      especially in carnivorous fishes. Manipulation of protein content by plant
      breeding can improve the digestibility rate of plant proteins in fish, but the
      identification of low digestibility proteins is essential. A reduction of low
      digestibility proteins will not only increase feed efficiency, but also reduce
      water pollution. Little is known about specific digestible protein profiles
      and/or molecular identification of more bioavailable plant proteins in fish
      diets. In this study, we identified low digestibility L. luteus seed proteins
      using Atlantic salmon (Salmo salar) crude digestive enzymes in an in vitro assay.
      Low digestibility proteins were identified by comparing SDS-PAGE banding profiles
      of digested and non-digested lupin seed proteins. Gel image analysis detected a
      major 12 kDa protein band in both lupin meal and protein isolate digested
      products. The 12 kDa was confirmed by 2D-PAGE gels and the extracted protein was
      analyzed with an ion trap mass spectrometer in tandem mass mode. The MS/MS data
      showed that the 12 kDa low digestibility protein was a large chain
      deltaconglutin, a common seed storage protein of yellow lupin. Comparison of the
      protein band profiles between lupin meal and protein isolates showed that the
      isolatation process did not affect the low digestibility of the 12 kDa protein. 

PMID- 24278279
TI  - The use and functionality of electronic prescribing systems in english acute NHS
      trusts: a cross-sectional survey.
AB  - OBJECTIVES: To describe current use of electronic prescribing (EP) in English
      acute NHS hospital trusts, and the use of multiple EP systems within the same
      hospital. DESIGN: Descriptive cross-sectional postal survey. SETTING: Acute NHS
      hospital trusts in England. PARTICIPANTS: The survey was sent to chief
      pharmacists in all acute English NHS hospital trusts in 2011. Where trusts
      comprised multiple hospitals, respondents were asked to complete the
      questionnaire for their main acute hospital. MAIN OUTCOME MEASURES: Prevalence of
      EP use in acute NHS hospitals; number of different EP systems in each hospital;
      stages of the patient pathway in which EP used; extent of deployment across the
      hospital; comprehensiveness regarding the drugs prescribed; decision support
      functionalities used. RESULTS: We received responses from 101 trusts (61%).
      Seventy (69%) respondent hospitals had at least one form of EP in use. More than
      half (39;56%) of hospitals with EP had more than one system in use, representing
      60 different systems. The most common were systems used only for discharge
      prescribing, used in 48 (48% of respondent hospitals). Specialist chemotherapy EP
      systems were second most common (34; 34%). Sixteen specialist inpatient systems
      were used across 15 hospitals, most commonly in adult critical care. Only 13
      (13%) respondents used inpatient electronic prescribing across all adult medical
      and surgical wards. Overall, 24 (40%) systems were developed 'in-house'. Decision
      support functionality varied widely. CONCLUSIONS: It is UK government policy to
      encourage the adoption of EP in hospitals. Our work shows that EP is prevalent in
      English hospitals, although often in limited clinical areas and for limited types
      of prescribing. The diversity of systems in use, often within the same hospital,
      may create challenges for staff training and patient safety.

PMID- 24278280
TI  - An agent-based model of centralized institutions, social network technology, and
      revolution.
AB  - This paper sheds light on the general mechanisms underlying large-scale social
      and institutional change. We employ an agent-based model to test the impact of
      authority centralization and social network technology on preference
      falsification and institutional change. We find that preference falsification is
      increasing with centralization and decreasing with social network range. This
      leads to greater cascades of preference revelation and thus more institutional
      change in highly centralized societies and this effect is exacerbated at greater
      social network ranges. An empirical analysis confirms the connections that we
      find between institutional centralization, social radius, preference
      falsification, and institutional change. 

PMID- 24278281
TI  - Maternal obesity in early pregnancy and risk of adverse outcomes.
AB  - OBJECTIVES: To assess the role of the health consequences of maternal overweight
      and obesity at the start of pregnancy on gestational pathologies, delivery and
      newborn characteristics. METHODS: A cohort of pregnant women (n = 6.558) having
      delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC) in
      2008 has been studied. Outcomes were compared using multivariate analyses
      controlling for confounding variables. RESULTS: Compared to normoweight,
      overweight and obese women have greater risks of gestational diabetes mellitus
      (RR = 2.13 (95% CI: 1.52-2.98) and (RR = 2.85 (95% CI: 2.01-4.04), gestational
      hypertension (RR = 2.01 (95% CI: 1.27-3.19) and (RR = 4.79 (95% CI: 3.13-7.32)
      and preeclampsia (RR = 3.16 (95% CI: 1.12-8.91) and (RR = 8.80 (95% CI: 3.46
      22.40). Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI:
      1.25-3.27), polyhydramnios. (RR = 1.76 (95% CI: 1.03-2.99), tearing (RR = 1.24
      (95% CI: 1.05-1.46) and a lower risk of induced deliveries (RR = 0.83 (95% CI:
      0.72-0.95). Both groups have more frequently caesarean section (RR = 1.36 (95%
      CI: 1.14-1.63) and (RR = 1.84 (95% CI: 1.53-2.22) and manual placenta extraction
      (RR = 1.65 (95% CI: 1.28-2.11) and (RR = 1.77 (95% CI: 1.35-2.33). Newborns from
      overweight and obese women have higher weight (p<0.001) and a greater risk of
      being macrosomic (RR = 2.00 (95% CI: 1.56-2.56) and (RR = 2.74 (95% CI: 2.12
      3.54). Finally, neonates from obese mother have a higher risk of being admitted
      to special care units (RR = 1.34 (95% CI: 1.01-1.77). Apgar 1 min was
      significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62
      8.69) than from overweight: 8.56 (95% CI: 8.50-8.61) or obese mothers: 8.48 (95%
      CI: 8.41-8.54). CONCLUSION: Obesity and overweight status at the beginning of
      pregnancy increase the adverse outcomes of the pregnancy. It is important to
      promote the normalization of bodyweight in those women who intend to get pregnant
      and to provide appropriate advice to the obese women of the risks of obesity at
      the start of the pregnancy.

PMID- 24278282
TI  - The phylogeny and biogeographic history of ashes (fraxinus, oleaceae) highlight
      the roles of migration and vicariance in the diversification of temperate trees.
AB  - The cosmopolitan genus Fraxinus, which comprises about 40 species of temperate
      trees and shrubs occupying various habitats in the Northern Hemisphere,
      represents a useful model to study speciation in long-lived angiosperms. We used
      nuclear external transcribed spacers (nETS), phantastica gene sequences, and two
      chloroplast loci (trnH-psbA and rpl32-trnL) in combination with previously
      published and newly obtained nITS sequences to produce a time-calibrated multi
      locus phylogeny of the genus. We then inferred the biogeographic history and
      evolution of floral morphology. An early dispersal event could be inferred from
      North America to Asia during the Oligocene, leading to the diversification of the
      section Melioides sensus lato. Another intercontinental dispersal originating
      from the Eurasian section of Fraxinus could be dated from the Miocene and
      resulted in the speciation of F. nigra in North America. In addition, vicariance
      was inferred to account for the distribution of the other Old World species
      (sections Sciadanthus, Fraxinus and Ornus). Geographic speciation likely
      involving dispersal and vicariance could also be inferred from the phylogenetic
      grouping of geographically close taxa. Molecular dating suggested that the
      initial divergence of the taxonomical sections occurred during the middle and
      late Eocene and Oligocene periods, whereas diversification within sections
      occurred mostly during the late Oligocene and Miocene, which is consistent with
      the climate warming and accompanying large distributional changes observed during
      these periods. These various results underline the importance of dispersal and
      vicariance in promoting geographic speciation and diversification in Fraxinus.
      Similarities in life history, reproductive and demographic attributes as well as
      geographical distribution patterns suggest that many other temperate trees should
      exhibit similar speciation patterns. On the other hand, the observed parallel
      evolution and reversions in floral morphology would imply a major influence of
      environmental pressure. The phylogeny obtained and its biogeographical
      implications should facilitate future studies on the evolution of complex
      adaptive characters, such as habitat preference, and their possible roles in
      promoting divergent evolution in trees. 

PMID- 24278283
TI  - Control of directionality in Streptomyces phage phiBT1 integrase-mediated site
      specific recombination.
AB  - Streptomyces phage phiBT1 integrates its genome into the attB site of the host
      chromosome with the attP site to generate attL and attR. The phiBT1 integrase
      belongs to the large serine recombinase subfamily which directly binds to target
      sites to initiate double strand breakage and exchange. A recombination
      directionality factor (RDF) is commonly required for switching integration to
      excision. Here we report the characterization of the RDF protein for phiBT1
      recombination. The RDF, is a phage-encoded gp3 gene product (28 KDa), which
      allows efficient active excision between attL and attR, and inhibits integration
      between attB and attP; Gp3 can also catalyze topological relaxation with the
      integrase of supercoiled plasmids containing a single excision site. Further
      study showed that Gp3 could form a dimer and interact with the integrase whether
      it bound to the substrate or not. The synapse formation of attL or attR alone
      with integrase and Gp3 showed that synapsis did not discriminate between the two
      sites, indicating that complementarity of central dinucleotides is the sole
      determinant of outcome in correct excision synapses. Furthermore, both in vitro
      and in vivo evidence support that the RDFs of phiBT1 and phiC31 were fully
      exchangeable, despite the low amino acid sequence identity of the two integrases.

PMID- 24278284
TI  - Mutational and structural analyses of Caldanaerobius polysaccharolyticus Man5B
      reveal novel active site residues for family 5 glycoside hydrolases.
AB  - CpMan5B is a glycoside hydrolase (GH) family 5 enzyme exhibiting both beta-1,4
      mannosidic and beta-1,4-glucosidic cleavage activities. To provide insight into
      the amino acid residues that contribute to catalysis and substrate specificity,
      we solved the structure of CpMan5B at 1.6 A resolution. The structure revealed
      several active site residues (Y12, N92 and R196) in CpMan5B that are not present
      in the active sites of other structurally resolved GH5 enzymes. Residue R196 in
      GH5 enzymes is thought to be strictly conserved as a histidine that participates
      in an electron relay network with the catalytic glutamates, but we show that an
      arginine fulfills a functionally equivalent role and is found at this position in
      every enzyme in subfamily GH5_36, which includes CpMan5B. Residue N92 is required
      for full enzymatic activity and forms a novel bridge over the active site that is
      absent in other family 5 structures. Our data also reveal a role of Y12 in
      establishing the substrate preference for CpMan5B. Using these molecular
      determinants as a probe allowed us to identify Man5D from Caldicellulosiruptor
      bescii as a mannanase with minor endo-glucanase activity. 

PMID- 24278285
TI  - Helicase-like transcription factor (Hltf) regulates G2/M transition,
      Wt1/Gata4/Hif-1a cardiac transcription networks, and collagen biogenesis.
AB  - HLTF/Hltf regulates transcription, remodels chromatin, and coordinates DNA damage
      repair. Hltf is expressed in mouse brain and heart during embryonic and postnatal
      development. Silencing Hltf is semilethal. Seventy-four percent of congenic
      C57BL/6J Hltf knockout mice died, 75% within 12-24 hours of birth. Previous
      studies in neonatal (6-8 hour postpartum) brain revealed silencing Hltf disrupted
      cell cycle progression, and attenuated DNA damage repair. An RNA-Seq snapshot of
      neonatal heart transcriptome showed 1,536 of 20,000 total transcripts were
      altered (p < 0.05) - 10 up- and 1,526 downregulated. Pathway enrichment analysis
      with MetaCoreTM showed Hltf's regulation of the G2/M transition (p=9.726E(-15))
      of the cell cycle in heart is nearly identical to its role in brain. In addition,
      Brca1 and 12 members of the Brca1 associated genome surveillance complex are also
      downregulated. Activation of caspase 3 coincides with transcriptional repression
      of Bcl-2. Hltf loss caused downregulation of Wt1/Gata4/Hif-1a signaling cascades
      as well as Myh7b/miR499 transcription. Hltf-specific binding to promoters and/or
      regulatory regions of these genes was authenticated by ChIP-PCR. Hif-1a targets
      for prolyl (P4ha1, P4ha2) and lysyl (Plod2) collagen hydroxylation, PPIase
      enzymes (Ppid, Ppif, Ppil3) for collagen trimerization, and lysyl oxidase (Loxl2)
      for collagen-elastin crosslinking were downregulated. However, transcription of
      genes for collagens, fibronectin, Mmps and their inhibitors (Timps) was
      unaffected. The collective downregulation of genes whose protein products control
      collagen biogenesis caused disorganization of the interstitial and perivascular
      myocardial collagen fibrillar network as viewed with picrosirius red-staining,
      and authenticated with spectral imaging. Wavy collagen bundles in control hearts
      contrasted with collagen fibers that were thin, short and disorganized in Hltf
      null hearts. Collagen bundles in Hltf null hearts were tangled and fragmented.
      Thus, silencing Hltf during heart organogenesis compromised DNA double-strand
      break repair, and caused aberrant collagen biogenesis altering the structural
      network that transmits cardiomyocyte force into muscle contraction. 

PMID- 24278286
TI  - Changes in the inflammatory response to injury and its resolution during the loss
      of regenerative capacity in developing Xenopus limbs.
AB  - Tissue and organ regeneration, unlike development, involves an injury that in
      postembryonic animals triggers inflammation followed by resolution. How
      inflammation affects epimorphic regeneration is largely uninvestigated. Here we
      examine inflammation and its resolution in Xenopus laevis hindlimb regeneration,
      which declines during larval development. During the first 5 days postamputation,
      both regeneration-competent stage 53 and regeneration-deficient stage 57
      hindlimbs showed very rapid accumulation of leukocytes and cells expressing
      interleukin-1beta and matrix metalloproteinase 9. Expression of genes for factors
      mediating inflammatory resolution appeared more persistent at stages 55 and 57
      than at stage 53, suggesting changes in this process during development. FoxP3, a
      marker for regulatory T cells, was upregulated by amputation in limbs at all
      three stages but only persisted at stage 57, when it was also detected before
      amputation. Expression of genes for cellular reprogramming, such as SALL4, was
      upregulated in limbs at all 3 stages, but markers of limb patterning, such as
      Shh, were expressed later and less actively after amputation in regeneration
      deficient limbs. Topical application of specific proinflammatory agents to
      freshly amputated limbs increased interleukin-1beta expression locally. With
      aqueous solutions of the proinflammatory metal beryllium sulfate, this effect
      persisted through 7 days postamputation and was accompanied by inhibition of
      regeneration. In BeSO4-treated limbs expression of markers for both inflammation
      and resolution, including FoxP3, was prolonged, while genes for cellular
      reprogramming were relatively unaffected and those for limb patterning failed to
      be expressed normally. These data imply that in Xenopus hindlimbs postamputation
      inflammation and its resolution change during development, with little effect on
      cellular dedifferentiation or reprogramming, but potentially interfering with the
      expression of genes required for blastema patterning. The results suggest that
      developmental changes in the larval anuran immune system may be involved in the
      ontogenetic loss of epimorphic regeneration in this system. 

PMID- 24278287
TI  - Simple sequence repeats together with mismatch repair deficiency can bias
      mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the
      airways of cystic fibrosis (CF) patients and undergoes a process of genetic
      adaptation based on mutagenesis. We evaluated the role of mononucleotide G:C and
      A:T simple sequence repeats (SSRs) in this adaptive process. An in silico survey
      of the genome sequences of 7 P. aeruginosa strains showed that mononucleotide G:C
      SSRs but not A:T SSRs were greatly under-represented in coding regions,
      suggesting a strong counterselection process for G:C SSRs with lengths >5 bp but
      not for A:T SSRs. A meta-analysis of published whole genome sequence data for a
      P. aeruginosa strain from a CF patient with chronic airway infection showed that
      G:C SSRs but not A:T SSRs were frequently mutated during the infection process
      through the insertion or deletion of one or more SSR subunits. The mutation
      tendency of G:C SSRs was length-dependent and increased exponentially as a
      function of SSR length. When this strain naturally became a stable Mismatch
      Repair System (MRS)-deficient mutator, the degree of increase of G:C SSRs
      mutations (5-fold) was much higher than that of other types of mutation (2.2-fold
      or less). Sequence analysis of several mutated genes reported for two different
      collections, both containing mutator and non-mutator strains of P. aeruginosa
      from CF chronic infections, showed that the proportion of G:C SSR mutations was
      significantly higher in mutators than in non-mutators, whereas no such difference
      was observed for A:T SSR mutations. Our findings, taken together, provide genome
      scale evidences that under a MRS-deficient background, long G:C SSRs are able to
      stochastically bias mutagenic pathways by making the genes in which they are
      harbored more prone to mutation. The combination of MRS deficiency and virulence
      related genes that contain long G:C SSRs is therefore a matter of concern in P.
      aeruginosa CF chronic infection. 

PMID- 24278288
TI  - Proteinuria independently predicts unfavorable outcome of ischemic stroke
      patients receiving intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: Patients with low estimated glomerular filtration rate
      (eGFR) and proteinuria may be at increased risk for stroke. This study
      investigated whether low eGFR and proteinuria are outcome predictors in stroke
      patients treated with intravenous thrombolysis. METHODS: We studied 432
      consecutive stroke patients who received thrombolysis from January 2006 to
      December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin
      scale >=2 at 3 months after stroke. Proteinuria was classified as negative or
      trace, mild, and moderate to severe. Using logistic regression analysis, we
      identified independent factors for unfavorable outcome after thrombolysis.
      RESULTS: Of all patients, 32.7% had proteinuria. Patients with proteinuria were
      older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial
      fibrillation, lower eGFR, and greater severity of stroke upon admission than
      those without proteinuria. Proteinuria, not low eGFR, was an independent
      predictor for unfavorable outcome for stroke (OR = 2.00 for mild proteinuria, p =
      0.035; OR = 2.54 for moderate to severe proteinuria, p = 0.035). However, no
      clear relationship was found between proteinuria and symptomatic hemorrhage after
      thrombolysis. CONCLUSIONS: Proteinuria is an independent predictor of unfavorable
      outcome for acute ischemic stroke in patients treated with intravenous
      thrombolysis, indicating the crucial role of chronic kidney disease on the
      effectiveness of thrombolysis.

PMID- 24278289
TI  - FOXC2 mutations in familial and sporadic spinal extradural arachnoid cyst.
AB  - Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that
      protrudes into the epidural space from a defect in the dura mater. Most cases are
      sporadic; however, three familial SEDAC cases have been reported, suggesting
      genetic etiological factors. All familial cases are associated with lymphedema
      distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation
      analysis has been performed in only 1 family, and no mutation analysis has been
      performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects
      consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by
      Sanger sequencing and structural abnormalities by TaqMan copy number assay. We
      identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance
      was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC
      caused by the heterozygous FOXC2 loss-of-function mutation should be considered a
      feature of LDS, although it often manifests as the sole symptom. Seven sporadic
      SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing
      clinical characteristics from those who had FOXC2 mutations, suggesting that
      other gene(s) besides FOXC2 are likely to be involved in SEDAC. 

PMID- 24278290
TI  - SEPP1 influences breast cancer risk among women with greater native american
      ancestry: the breast cancer health disparities study.
AB  - Selenoproteins are a class of proteins containing a selenocysteine residue, many
      of which have been shown to have redox functions, acting as antioxidants to
      decrease oxidative stress. Selenoproteins have previously been associated with
      risk of various cancers and redox-related diseases. In this study we evaluated
      possible associations between breast cancer risk and survival and single
      nucleotide polymorphisms (SNPs) in the selenoprotein genes GPX1, GPX2, GPX3,
      GPX4, SELS, SEP15, SEPN1, SEPP1, SEPW1, TXNRD1, and TXNRD2 among Hispanic/Native
      American (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases,
      1586 controls) women in the Breast Cancer Health Disparities Study. Adaptive Rank
      Truncated Product (ARTP) analysis was used to determine both gene and pathway
      significance with these genes. The overall selenoprotein pathway PARTP was not
      significantly associated with breast cancer risk (PARTP = 0.69), and only one
      gene, GPX3, was of borderline significance for the overall population (PARTP
      =0.09) and marginally significant among women with 0-28% Native American (NA)
      ancestry (PARTP=0.06). The SEPP1 gene was statistically significantly associated
      with breast cancer risk among women with higher NA ancestry (PARTP=0.002) and
      contributed to a significant pathway among those women (PARTP=0.04). GPX1, GPX3,
      and SELS were associated with Estrogen Receptor-/Progesterone Receptor+ status
      (PARTP = 0.002, 0.05, and 0.01, respectively). Four SNPs (GPX3 rs2070593, rsGPX4
      rs2074451, SELS rs9874, and TXNRD1 rs17202060) significantly interacted with
      dietary oxidative balance score after adjustment for multiple comparisons to
      alter breast cancer risk. GPX4 was significantly associated with breast cancer
      survival among those with the highest NA ancestry (PARTP = 0.05) only. Our data
      suggest that SEPP1 alters breast cancer risk among women with higher levels of NA
      ancestry. 

PMID- 24278291
TI  - Changes in cerebral blood flow during olfactory stimulation in patients with
      multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.
AB  - Multiple chemical sensitivity (MCS) is characterized by somatic distress upon
      exposure to odors. Patients with MCS process odors differently from controls.
      This odor-processing may be associated with activation in the prefrontal area
      connecting to the anterior cingulate cortex, which has been suggested as an area
      of odorant-related activation in MCS patients. In this study, activation was
      defined as a significant increase in regional cerebral blood flow (rCBF) because
      of odorant stimulation. Using the well-designed card-type olfactory test kit,
      changes in rCBF in the prefrontal cortex (PFC) were investigated after olfactory
      stimulation with several different odorants. Near-infrared spectroscopic (NIRS)
      imaging was performed in 12 MCS patients and 11 controls. The olfactory
      stimulation test was continuously repeated 10 times. The study also included
      subjective assessment of physical and psychological status and the perception of
      irritating and hedonic odors. Significant changes in rCBF were observed in the
      PFC of MCS patients on both the right and left sides, as distinct from the center
      of the PFC, compared with controls. MCS patients adequately distinguished the non
      odorant in 10 odor repetitions during the early stage of the olfactory
      stimulation test, but not in the late stage. In comparison to controls, autonomic
      perception and negative affectivity were poorer in MCS patients. These results
      suggest that prefrontal information processing associated with odor-processing
      neuronal circuits and memory and cognition processes from past experience of
      chemical exposure play significant roles in the pathology of this disorder. 

PMID- 24278292
TI  - Novel pancreatic cancer cell lines derived from genetically engineered mouse
      models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and
      therapy.
AB  - Pancreatic cancer (PC) remains one of the most lethal human malignancies with
      poor prognosis. Despite all advances in preclinical research, there have not been
      significant translation of novel therapies into the clinics. The development of
      genetically engineered mouse (GEM) models that produce spontaneous pancreatic
      adenocarcinoma (PDAC) have increased our understanding of the pathogenesis of the
      disease. Although these PDAC mouse models are ideal for studying potential
      therapies and specific genetic mutations, there is a need for developing
      syngeneic cell lines from these models. In this study, we describe the successful
      establishment and characterization of three cell lines derived from two (PDAC)
      mouse models. The cell line UN-KC-6141 was derived from a pancreatic tumor of a
      Kras(G12D);Pdx1-Cre (KC) mouse at 50 weeks of age, whereas UN-KPC-960 and UN-KPC
      961 cell lines were derived from pancreatic tumors of
      Kras(G12D);Trp53(R172H);Pdx1-Cre (KPC) mice at 17 weeks of age. The cancer
      mutations of these parent mice carried over to the daughter cell lines (i.e.
      Kras(G12D) mutation was observed in all three cell lines while Trp53 mutation was
      observed only in KPC cell lines). The cell lines showed typical cobblestone
      epithelial morphology in culture, and unlike the previously established mouse
      PDAC cell line Panc02, expressed the ductal marker CK19. Furthermore, these cell
      lines expressed the epithelial-mesenchymal markers E-cadherin and N-cadherin, and
      also, Muc1 and Muc4 mucins. In addition, these cell lines were resistant to the
      chemotherapeutic drug Gemcitabine. Their implantation in vivo produced
      subcutaneous as well as tumors in the pancreas (orthotopic). The genetic
      mutations in these cell lines mimic the genetic compendium of human PDAC, which
      make them valuable models with a high potential of translational relevance for
      examining diagnostic markers and therapeutic drugs. 

PMID- 24278293
TI  - High incidence of tuberculosis, low sensitivity of current diagnostic scheme and
      prolonged culture positivity in four colombian prisons. A cohort study.
AB  - OBJECTIVE: To determine the incidence of pulmonary tuberculosis (TB) in inmates,
      factors associated with TB, and the time to sputum smear and culture conversion
      during TB treatment. METHODS: Prospective cohort study. All prisoners with
      respiratory symptoms (RS) of any duration were evaluated. After participants
      signed consent forms, we collected three spontaneous sputum samples on
      consecutive days. We performed auramine-rhodamine staining, culturing with the
      thin-layer agar method, Lowestein-Jensen medium and MGIT, susceptibility testing
      for first-line drugs; and HIV testing. TB cases were followed, and the times to
      smear and culture conversion to negative were evaluated. RESULTS: Of 9,507
      prisoners held in four prisons between April/30/2010 and April/30/2012, among
      them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of
      any duration, and 72 were diagnosed with TB. The annual incidence was 505
      cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15
      days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with
      a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB,
      contact with a TB case, and being underweight were risk factors associated with
      TB. Overweight was a protective factor. Almost a quarter of TB cases were
      detected only by culture; three cases were isoniazid resistant, and two resistant
      to streptomycin. The median times to culture conversion was 59 days, and smear
      conversion was 33. CONCLUSIONS: The TB incidence in prisons is 20 times higher
      than in the general Colombian population. TB should be considered in inmates with
      lower RS of any duration. Our data demonstrate that patients receiving adequate
      anti-TB treatment remain infectious for prolonged periods. These findings suggest
      that current recommendations regarding isolation of prisoners with TB should be
      reconsidered, and suggest the need for mycobacterial cultures during follow-up.

PMID- 24278294
TI  - Commensal bacteria-dependent indole production enhances epithelial barrier
      function in the colon.
AB  - Microbiota have been shown to have a great influence on functions of intestinal
      epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule
      mediating intercellular signals in bacteria has been well appreciated. However,
      it remains unknown whether indole has beneficial effects on maintaining
      intestinal barriers in vivo. In this study, we analyzed the effect of indole on
      ECs using a germ free (GF) mouse model. GF mice showed decreased expression of
      junctional complex molecules in colonic ECs. The feces of specific pathogen-free
      (SPF) mice contained a high amount of indole; however the amount was
      significantly decreased in the feces of GF mice by 27-fold. Oral administration
      of indole-containing capsules resulted in increased expression of both tight
      junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in
      GF mice. In accordance with the increased expression of these junctional complex
      molecules, GF mice given indole-containing capsules showed higher resistance to
      dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of
      indole on DSS-induced epithelial damage was also observed in mice bred in SPF
      conditions. These findings highlight the beneficial role of indole in
      establishing an epithelial barrier in vivo. 

PMID- 24278295
TI  - Postnatal constant light compensates Cryptochrome1 and 2 double deficiency for
      disruption of circadian behavioral rhythms in mice under constant dark.
AB  - Clock genes Cryptochrome (Cry1) and Cry2 are essential for expression of
      circadian rhythms in mice under constant darkness (DD). However, circadian
      rhythms in clock gene Per1 expression or clock protein PER2 are detected in the
      cultured suprachiasmatic nucleus (SCN) of neonatal Cry1 and Cry2 double deficient
      (Cry1 (-/-)/Cry2 (-/-)) mice. A lack of circadian rhythms in adult Cry1 (-/
      )/Cry2 (-/-) mice is most likely due to developmentally disorganized cellular
      coupling of oscillating neurons in the SCN. On the other hand, neonatal rats
      exposed to constant light (LL) developed a tenable circadian system under
      prolonged LL which was known to fragment circadian behavioral rhythms. In the
      present study, Cry1 (-/-)/Cry2 (-/-) mice were raised under LL from postnatal day
      1 for 7 weeks and subsequently exposed to DD for 3 weeks. Spontaneous movement
      was monitored continuously after weaning and PER2::LUC was measured in the
      cultured SCN obtained from mice under prolonged DD. Surprisingly, Chi square
      periodogram analysis revealed significant circadian rhythms of spontaneous
      movement in the LL-raised Cry1 (-/-)/Cry2 (-/-) mice, but failed to detect the
      rhythms in Cry1 (-/-)/Cry2 (-/-) mice raised under light-dark cycles (LD). By
      contrast, prolonged LL in adulthood did not rescue the circadian behavioral
      rhythms in the LD raised Cry1 (-/-)/Cry2 (-/-) mice. Visual inspection disclosed
      two distinct activity components with different periods in behavioral rhythms of
      the LL-raised Cry1(-/-)/Cry2(-/-) mice under DD: one was shorter and the other
      was longer than 24 hours. The two components repeatedly merged and separated. The
      patterns resembled the split behavioral rhythms of wild type mice under prolonged
      LL. In addition, circadian rhythms in PER2::LUC were detected in some of the LL
      raised Cry1(-/-)/Cry2(-/-) mice under DD. These results indicate that neonatal
      exposure to LL compensates the CRY double deficiency for the disruption of
      circadian behavioral rhythms under DD in adulthood. 

PMID- 24278296
TI  - Olfactory sensitivity for six predator odorants in CD-1 mice, human subjects, and
      spider monkeys.
AB  - Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1
      mice (Mus musculus) for six sulfur-containing odorants known to be components of
      the odors of natural predators of the mouse. With all six odorants, the mice
      discriminated concentrations <0.1 ppm (parts per million) from the solvent, and
      with five of the six odorants the best-scoring animals were even able to detect
      concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles
      geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found
      to detect the same six odorants at concentrations <0.01 ppm, and with four of the
      six odorants the best-scoring animals and subjects even detected concentrations
      <10 ppt. With all three species, the threshold values obtained here are generally
      lower than (or in the lower range of) those reported for other chemical classes
      tested previously, suggesting that sulfur-containing odorants may play a special
      role in olfaction. Across-species comparisons showed that the mice were
      significantly more sensitive than the human subjects and the spider monkeys with
      four of the six predator odorants. However, the human subjects were significantly
      more sensitive than the mice with the remaining two odorants. Human subjects and
      spider monkeys significantly differed in their sensitivity with only two of the
      six odorants. These comparisons lend further support to the notion that the
      number of functional olfactory receptor genes or the relative or absolute size of
      the olfactory bulbs are poor predictors of a species' olfactory sensitivity.
      Analysis of odor structure-activity relationships showed that in both mice and
      human subjects the type of alkyl rest attached to a thietane and the type of
      oxygen moiety attached to a thiol significantly affected olfactory sensitivity. 

PMID- 24278297
TI  - Functional IL-23R rs10889677 genetic polymorphism and risk of multiple solid
      tumors: a meta-analysis.
AB  - Interleukin-23 receptor (IL23R) can interact with IL-23 and, thus, is involved in
      the T-helper 17 (Th17) cell-mediated inflammatory process as well as
      tumorigenesis. Recently, a functional single nucleotide polymorphism (SNP)
      rs10889677 has been identified in the 3'-untranslated region of IL-23R. It has
      been showed that the rs10889677AC SNP could increase the binding affinity of
      microRNA let-7f and downregulate IL-23R expression. Several case-control studies
      have examined the association between this SNP and genetic susceptibility of
      multiple solid tumors. However, the conclusions are conflicting. Therefore, we
      conducted this meta-analysis to systematically study the role of this functional
      IL-23R SNP in development of multiple solid tumors. There are a total of 5
      studies are eligible (6731 cases and 7296 healthy controls). Either fixed-effect
      model or random-effect model was used to calculate pooled odds ratios (ORs) and
      the 95% confidence interval (95% CI). Significant association between this
      functional rs10889677 genetic variant and risk of multiple solid tumors were
      observed (CC genotype vs. AA genotype: OR = 0.59, 95% CI = 0.53-0.66, P < 0.001).
      These findings demonstrated that the IL-23R rs10889677 genetic variant might play
      an important part during malignant transformation of multiple solid tumors. 

PMID- 24278298
TI  - Maximum allowed solvent accessibilites of residues in proteins.
AB  - The relative solvent accessibility (RSA) of a residue in a protein measures the
      extent of burial or exposure of that residue in the 3D structure. RSA is
      frequently used to describe a protein's biophysical or evolutionary properties.
      To calculate RSA, a residue's solvent accessibility (ASA) needs to be normalized
      by a suitable reference value for the given amino acid; several normalization
      scales have previously been proposed. However, these scales do not provide tight
      upper bounds on ASA values frequently observed in empirical crystal structures.
      Instead, they underestimate the largest allowed ASA values, by up to 20%. As a
      result, many empirical crystal structures contain residues that seem to have RSA
      values in excess of one. Here, we derive a new normalization scale that does
      provide a tight upper bound on observed ASA values. We pursue two complementary
      strategies, one based on extensive analysis of empirical structures and one based
      on systematic enumeration of biophysically allowed tripeptides. Both approaches
      yield congruent results that consistently exceed published values. We conclude
      that previously published ASA normalization values were too small, primarily
      because the conformations that maximize ASA had not been correctly identified. As
      an application of our results, we show that empirically derived hydrophobicity
      scales are sensitive to accurate RSA calculation, and we derive new
      hydrophobicity scales that show increased correlation with experimentally
      measured scales. 

PMID- 24278299
TI  - A novel antibody humanization method based on epitopes scanning and molecular
      dynamics simulation.
AB  - 1-17-2 is a rat anti-human DEC-205 monoclonal antibody that induces
      internalization and delivers antigen to dendritic cells (DCs). The potentially
      clinical application of this antibody is limited by its murine origin.
      Traditional humanization method such as complementarity determining regions
      (CDRs) graft often leads to a decreased or even lost affinity. Here we have
      developed a novel antibody humanization method based on computer modeling and
      bioinformatics analysis. First, we used homology modeling technology to build the
      precise model of Fab. A novel epitope scanning algorithm was designed to identify
      antigenic residues in the framework regions (FRs) that need to be mutated to
      human counterpart in the humanization process. Then virtual mutation and
      molecular dynamics (MD) simulation were used to assess the conformational impact
      imposed by all the mutations. By comparing the root-mean-square deviations
      (RMSDs) of CDRs, we found five key residues whose mutations would destroy the
      original conformation of CDRs. These residues need to be back-mutated to rescue
      the antibody binding affinity. Finally we constructed the antibodies in vitro and
      compared their binding affinity by flow cytometry and surface plasmon resonance
      (SPR) assay. The binding affinity of the refined humanized antibody was similar
      to that of the original rat antibody. Our results have established a novel method
      based on epitopes scanning and MD simulation for antibody humanization. 

PMID- 24278300
TI  - Cell walls and the developmental anatomy of the Brachypodium distachyon stem
      internode.
AB  - While many aspects of plant cell wall polymer structure are known, their spatial
      and temporal distribution within the stem are not well understood. Here, we
      studied vascular system and fiber development, which has implication for both
      biofuel feedstock conversion efficiency and crop yield. The subject of this
      study, Brachypodium distachyon, has emerged as a grass model for food and energy
      crop research. Here, we conducted our investigation using B. distachyon by
      applying various histological approaches and Fourier transform infrared
      spectroscopy to the stem internode from three key developmental stages. While
      vascular bundle size and number did not change over time, the size of the
      interfascicular region increased dramatically, as did cell wall thickness. We
      also describe internal stem internode anatomy and demonstrate that lignin
      deposition continues after crystalline cellulose and xylan accumulation ceases.
      The vascular bundle anatomy of B. distachyon appears to be highly similar to
      domesticated grasses. While the arrangement of bundles within the stem is highly
      variable across grasses, B. distachyon appears to be a suitable model for the
      rind of large C4 grass crops. A better understanding of growth and various
      anatomical and cell wall features of B. distachyon will further our understanding
      of plant biomass accumulation processes. 

PMID- 24278302
TI  - Effects of dominant/subordinate social status on formalin-induced pain and
      changes in serum proinflammatory cytokine concentrations in mice.
AB  - Current investigations regarding social stress primarily focus on the health
      consequences of being in stressful social hierarchies. The repetitive nature of
      social conflicts seems to favor an induction of hyperalgesia or hypoalgesia, both
      in rodents and humans. Additionally, social conflicts may affect the immune
      system. In order to better establish the pain and immune responses to stress, the
      present study implemented a sensory contact model on 32 male BALB/c mice.
      Subsequent to establishing a dominance/submissive social relationship, each mouse
      was injected with formalin (20 MUl, 2%) and their pain behavior was scored and
      serum concentrations of proinflammatory cytokines IL-1 and IL-6, and
      corticosterone were also measured. Test results revealed that subordinate mice
      were hypoalgesic during chronic phase of formalin test compared to control and
      dominant mice (P<0.05). On the other hand, subordinate mice were hyperalgesic
      compared to dominant mice during the whole acute phase of formalin test (P<0.05).
      Corticosterone, IL-1 and IL-6 concentrations were much higher in serum of
      dominant and subordinate mice than in the control group (p<0.05). The results
      indicated that, although both dominant and subordinate animals displayed an
      increase in serum corticosterone and proinflammatory cytokines during social
      interactions, their response to pain perception differently was affected with the
      social status. 

PMID- 24278303
TI  - Treating adrenal tumors in 26 patients with CyberKnife: a mono-institutional
      experience.
AB  - BACKGROUND: CyberKnife (CK) is a novel stereotactic radiosurgery system for
      treating tumors in any part of the body. It is a non-invasive or minimally
      invasive tumor treatment modality that can deliver high doses of spatially
      precise radiation and minimize exposure to neighboring healthy tissues or vital
      organs. The purpose of this study was to investigate the safety and efficacy of
      CK in the treatment of adrenal tumors. METHODS AND RESULTS: We performed a
      retrospective analysis of 26 patients with adrenal tumors who had been treated
      with CK in the radiotherapy center of our hospital between March 2009 and March
      2012. Eight patients had primary adrenal tumors and 18 patients had metastatic
      adrenal tumors. In addition to CK, 4 patients received chemotherapy and 2
      patients received immunotherapy. The average tumor volume was 72.1 cm(3) and the
      prescribed radiation dosage ranged from 30 to 50 Gy and was fractionated 3 to 5
      times with a 58% to 80% isodose line. Abdominal CT was performed between 1 to 3
      months after the CK treatment to evaluate the short-term efficacy with follow-up
      examinations once every 3 months. Three patients had complete remission, 12
      patients had partial remission, 5 patients had stable disease, and 6 patients had
      progressive illness. The effective rate of pain relief was 93.8% and the disease
      control rate was 77% with a median overall survival of 17 months and a median
      progression-free survival of 14 months. Treatment Related toxicity was well
      tolerated, but preventative measure need to be taken for radiation enteritis.
      CONCLUSIONS: CK is safe and effective for treating adrenal tumors with few
      adverse reactions. Nonetheless, its long-term effects requires further follow-up.

PMID- 24278301
TI  - Studies on the expression of sesquiterpene synthases using promoter-beta
      glucuronidase fusions in transgenic Artemisia annua L.
AB  - In order to better understand the influence of sesquiterpene synthases on
      artemisinin yield in Artemisia annua, the expression of some sesquiterpene
      synthases has been studied using transgenic plants expressing promoter-GUS
      fusions. The cloned promoter sequences were 923, 1182 and 1510 bp for beta
      caryophyllene (CPS), epi-cedrol (ECS) and beta-farnesene (FS) synthase,
      respectively. Prediction of cis-acting regulatory elements showed that the
      promoters are involved in complex regulation of expression. Transgenic A. annua
      plants carrying promoter-GUS fusions were studied to elucidate the expression
      pattern of the three sesquiterpene synthases and compared to the previously
      studied promoter of amorpha-4,11-diene synthase (ADS), a key enzyme of
      artemisinin biosynthesis. The CPS and ECS promoters were active in T-shaped
      trichomes of leaves and stems, basal bracts of flower buds and also in some
      florets cells but not in glandular secretory trichome while FS promoter activity
      was only observed in leaf cells and trichomes of transgenic shoots. ADS, CPS, ECS
      and FS transcripts were induced by wounding in a time depended manner. The four
      sesquiterpene synthases may be involved in responsiveness of A. annua to
      herbivory. Methyl jasmonate treatment triggered activation of the promoters of
      all four sesquiterpene synthases in a time depended manner. Southern blot result
      showed that the GUS gene was inserted into genomic DNA of transgenic lines as a
      single copy or two copies. The relative amounts of CPS and ECS as well as
      germacrene A synthase (GAS) transcripts are much lower than that of ADS
      transcript. Consequently, down-regulation of the expression of the CPS, ECS or
      GAS gene may not improve artemsinin yield. However, blocking the expression of FS
      may have effects on artemisinin production. 

PMID- 24278304
TI  - A simulation-based assessment of strategies to control Clostridium difficile
      transmission and infection.
AB  - BACKGROUND: Clostridium difficile is one of the most common and important
      nosocomial pathogens, causing severe gastrointestinal disease in hospitalized
      patients. Although "bundled" interventions have been proposed and promoted,
      optimal control strategies remain unknown. METHODS: We designed an agent-based
      computer simulation of nosocomial C. difficile transmission and infection, which
      included components such as: patients and health care workers, and their
      interactions; room contamination via C. difficile shedding; C. difficile hand
      carriage and removal via hand hygiene; patient acquisition of C. difficile via
      contact with contaminated rooms or health care workers; and patient antimicrobial
      use. We then introduced six interventions, alone and "bundled" together:
      aggressive C. difficile testing; empiric isolation and treatment of symptomatic
      patients; improved adherence to hand hygiene and contact precautions; improved
      use of soap and water for hand hygiene; and improved environmental cleaning. All
      interventions were tested using values representing base-case, typical
      intervention, and optimal intervention scenarios. FINDINGS: In the base-case
      scenario, C. difficile infection rates ranged from 8-21 cases/10,000 patient
      days, with a case detection fraction between 32%-50%. Implementing the "bundle"
      at typical intervention levels had a large impact on C. difficile acquisition and
      infection rates, although intensifying the intervention to optimal levels had
      much less additional impact. Most of the impact came from improved hand hygiene
      and empiric isolation and treatment of suspected C. difficile cases. CONCLUSION:
      A "bundled" intervention is likely to reduce nosocomial C. difficile infection
      rates, even under typical implementation conditions. Real-world implementation of
      the "bundle" should focus on those components of the intervention that are likely
      to produce the greatest impact on C. difficile infection rates, such as hand
      hygiene and empiric isolation and treatment of suspected cases.

PMID- 24278305
TI  - An evaluation of association between a novel hippocampal biology related SNP
      (rs7294919) and schizophrenia.
AB  - Recent genetic analyses have implicated several candidate susceptibility variants
      for schizophrenia. The single nucleotide polymorphism (SNP) rs7294919 is likely a
      schizophrenia-susceptibility variant according to its significant association
      with hippocampal volume, hippocampus function, and cognitive performance as well
      as the nominal association with schizophrenia. However, all previous analyses
      were conducted only in Europeans, and whether rs7294919 is associated with
      schizophrenia in other populations are yet to be tested. Here, we conducted a
      case-control analysis of rs7294919 with schizophrenia in six independent Chinese
      (N = 3) and Japanese (N = 3) samples, including a total of 7,352 cases and 10,824
      controls. The results of our association analysis were not able to confirm the
      association of rs7294919 with schizophrenia (p = 0.51 in total samples, odds
      ratio = 1.02 for allele[C]). The absence of rs7294919's association in Chinese
      and Japanese suggest a potential genetic heterogeneity in the susceptibility of
      schizophrenia on this locus and also demonstrate the difficulties in replicating
      associations of schizophrenia across different ethnic populations.

PMID- 24278306
TI  - Effects of NR1H3 genetic variation on the expression of liver X receptor alpha
      and the progression of Alzheimer's disease.
AB  - Alzheimer's disease (AD) has been postulated to involve defects in the clearance
      of amyloid-beta (Abeta). Activation of liver X receptor alpha (LXRalpha)
      increases the expression of apolipoprotein E (ApoE) as well as cholesterol
      transporters ABCA1 and ABCG1, leading to augmented clearance of Abeta. We have
      previously shown that the C allele of rs7120118 in the NR1H3 gene encoding
      LXRalpha reduces the risk of AD. Here, we wanted to assess whether the rs7120118
      variation affects the progression of AD and modulates the expression of NR1H3 and
      its downstream targets APOE, ABCA1 and ABCG1.We utilized tissue samples from the
      inferior temporal cortex of 87 subjects, which were subdivided according to Braak
      staging into mild, moderate and severe AD groups on the basis of AD-related
      neurofibrillary pathology. APOE epsilon4 allele increased soluble Abeta42 levels
      in the tissue samples in a dose-dependent manner, but did not affect the
      expression status of APOE. In contrast, the CC genotype of rs7120118 was
      underrepresented in the severe group, although this result did not reach
      statistical significance. Also, patients with the CC genotype of rs7120118 showed
      significantly decreased soluble Abeta42 levels as compared to the patients with
      TT genotype. Although the severity of AD did not affect NR1H3 expression, the
      mRNA levels of NR1H3 among the patients with CT genotype of rs7120118 were
      significantly increased as compared to the patients with TT genotype. These
      results suggest that genetic variation in NR1H3 modulates the expression of
      LXRalpha and the levels of soluble Abeta42. 

PMID- 24278307
TI  - Modeling Alzheimer's disease in mouse without mutant protein overexpression:
      cooperative and independent effects of Abeta and tau.
AB  - BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia in the
      elderly, has two pathological hallmarks: Abeta plaques and aggregation of
      hyperphosphorylated tau (p-tau). Abeta is a cleavage product of Amyloid Precursor
      Protein (APP). Presenilin 1 (PS1) and presenilin 2 (PS2) are the catalytic
      subunit of gamma-secretase, which cleaves APP and mediates Abeta production.
      Genetic mutations in APP, PSEN1 or PSEN2 can lead to early onset of familial AD
      (FAD). Although mutations in the tau encoding gene MAPT leads to a subtype of
      frontotemporal dementia and these mutations have been used to model AD tauopathy,
      no MAPT mutations have been found to be associated with AD. RESULTS: To model AD
      pathophysiology in mice without the gross overexpression of mutant transgenes, we
      created a humanized AD mouse model by crossing the APP and PSEN1 FAD knock-in
      mice with the htau mice which express wildtype human MAPT genomic DNA on mouse
      MAPT null background (APP/PS1/htau). The APP/PS1/htau mice displayed mild, age
      dependent, Abeta plaques and tau hyperphosphorylation, thus successfully
      recapitulating the late-onset AD pathological hallmarks. Selected biochemical
      analyses, including p-tau western blot, gamma-secretase activity assay, and Abeta
      ELISA, were performed to study the interaction between Abeta and p-tau.
      Subsequent behavioral studies revealed that the APP/PS1/htau mice showed reduced
      mobility in old ages and exaggerated fear response. Genetic analysis suggested
      that the fear phenotype is due to a synergic interaction between Abeta and p-tau,
      and it can be completely abolished by tau deletion. CONCLUSION: The APP/PS1/htau
      model represents a valuable and disease-relevant late-onset pre-clinical AD
      animal model because it incorporates human AD genetics without mutant protein
      overexpression. Analysis of the mice revealed both cooperative and independent
      effects of Abeta and p-tau.

PMID- 24278308
TI  - Maternal treatment with agonistic autoantibodies against type-1 angiotensin II
      receptor in late pregnancy increases apoptosis of myocardial cells and myocardial
      susceptibility to ischemia-reperfusion injury in offspring rats.
AB  - Epidemiological studies have demonstrated that offspring born to mothers
      preeclampsia (PE) are at increased risk for developing cardiovascular diseases
      after birth, but the underlying mechanism is unknown. Angiotensin II receptor
      type 1 autoantibody (AT1-AA), an agonist acting via activation of the AT1
      receptor, is believed to be involved in the pathogenesis of both PE and fetal
      growth restriction. The aim of the present study was to confirm the hypothesis
      that prenatal AT1-AA exposure increases the heart susceptibility to
      ischemia/reperfusion injury (IRI) in the offspring in an AT1-AA-induced animal
      model of PE, and determine whether or not the increase of maternal AT1-AA level
      is a factor contributing to sustained abnormalities of the heart structure during
      infancy. The hearts of 45-day-old offspring rats were studied using Langendorff
      preparation to determine the susceptibility of the heart to IRI. The results
      showed that the body weight of the maternal rats was not significantly different
      between the study and control groups, but the body weight of their offspring in
      AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3
      after birth. Although the heart weight index was not significantly affected at
      all ages examined, AT1-AA significantly increased the size of myocardial cells of
      the left ventricle (LV) at the age of 45 days. AT1-AA gained access to fetal
      circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1
      AA also significantly delayed recovery from IRI and affected the LV function of
      45-day-old offspring. This was associated with a significant increase in IRI
      induced LV myocardial infarct size. These results suggest that AT1-AA induced
      abnormal apoptosis of fetal myocardial cells during the fetal period and
      increased the cardiac susceptibility to IRI in adult offspring. 

PMID- 24278310
TI  - Novel and highly efficient regioselective route to helicid esters by lipozyme
      TLL.
AB  - Highly regioselective acylation of helicid with fatty acid vinyl esters catalyzed
      by the lipase from Thermomyces lanuginosus has been successfully performed for
      the first time. For the enzymatic caproylation of helicid, under the optimal
      conditions, initial reaction rate was 33.2 mM/h, and substrate conversion and
      regioselectivity were greater than 99%. In addition, the acyl recognition of the
      enzyme in the regioselective acylation of helicid was investigated. The results
      showed that although 6'-O-acyl derivatives of helicid were exclusively obtained
      with all the tested acyl donors, the enzymatic reaction rate varied widely with
      different acyl donors, presumably owing to their different interactions with the
      active site of the lipase. It is also interesting that the different
      configuration of only one hydroxyl group at C-3 in helicid couldn't affect the
      lipase-catalyzed esterification and helicid has the same regioselectivity as that
      of D-glucose and arbutin. 

PMID- 24278309
TI  - Acetate supplementation induces growth arrest of NG2/PDGFRalpha-positive
      oligodendroglioma-derived tumor-initiating cells.
AB  - Cancer is associated with globally hypoacetylated chromatin and considerable
      attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate
      (NAA), the primary storage form of acetate in the brain, and aspartoacylase
      (ASPA), the enzyme responsible for NAA catalysis to generate acetate and
      ultimately acetyl-Coenzyme A for histone acetylation, are reduced in
      oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which
      increases histone acetylation and inhibits histone deacetylase expression, has
      been safely used for acetate supplementation in Canavan disease, a leukodystrophy
      due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest
      of oligodendroglioma-derived cells in vitro, without affecting normal cells.
      Sodium acetate, at doses comparable to that generated by complete GTA catalysis,
      but not glycerol also promoted growth arrest, whereas long chain triglycerides
      promoted cell growth. To begin to elucidate its mechanism of action, the effects
      of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of
      established human oligodendroglioma cells (HOG and Hs683) and primary tumor
      derived oligodendroglioma cells that exhibit some features of cancer stem cells
      (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line
      (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA
      synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated
      growth arrest was not associated with apoptosis or differentiation, but increased
      expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may
      provide a safe, novel epigenetic therapy to reduce the growth of
      oligodendroglioma cells without affecting normal neural stem or oligodendrocyte
      progenitor cell proliferation or differentiation. 

PMID- 24278311
TI  - Probing functional properties of nociceptive axons using a microfluidic culture
      system.
AB  - Pathological changes in axonal function are integral features of many
      neurological disorders, yet our knowledge of the molecular basis of axonal
      dysfunction remains limited. Microfluidic chambers (MFCs) can provide unique
      insight into the axonal compartment independent of the soma. Here we demonstrate
      how an MFC based cell culture system can be readily adapted for the study of
      axonal function in vitro. We illustrate the ease and versatility to assay
      electrogenesis and conduction of action potentials (APs) in naive, damaged or
      sensitized DRG axons using calcium imaging at the soma for pharmacological
      screening or patch-clamp electrophysiology for detailed biophysical
      characterisation. To demonstrate the adaptability of the system, we report by way
      of example functional changes in nociceptor axons following sensitization by
      neurotrophins and axotomy in vitro. We show that NGF can locally sensitize axonal
      responses to capsaicin, independent of the soma. Axotomizing neurons in MFC
      results in a significant increase in the proportion of neurons that respond to
      axonal stimulation, and interestingly leads to accumulation of Nav1.8 channels in
      regenerating axons. Axotomy also augmented AP amplitude following axotomy and
      altered activation thresholds in a subpopulation of regenerating axons. We
      further show how the system can readily be used to study modulation of axonal
      function by non-neuronal cells such as keratinocytes. Hence we describe a novel
      in vitro platform for the study of axonal function and a surrogate model for
      nerve injury and sensitization. 

PMID- 24278312
TI  - Defining the range of pathogens susceptible to Ifitm3 restriction using a
      knockout mouse model.
AB  - The interferon-inducible transmembrane (IFITM) family of proteins has been shown
      to restrict a broad range of viruses in vitro and in vivo by halting progress
      through the late endosomal pathway. Further, single nucleotide polymorphisms
      (SNPs) in its sequence have been linked with risk of developing severe influenza
      virus infections in humans. The number of viruses restricted by this host protein
      has continued to grow since it was first demonstrated as playing an antiviral
      role; all of which enter cells via the endosomal pathway. We therefore sought to
      test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse
      model. We showed that Ifitm3 does not impact on the restriction or pathogenesis
      of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium
      tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro
      evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus
      (RSV) in vivo either through directly restricting RSV cell infection, or by
      exerting a previously uncharacterised function controlling disease pathogenesis.
      This represents the first demonstration of a virus that enters directly through
      the plasma membrane, without the need for the endosomal pathway, being restricted
      by the IFITM family; therefore further defining the role of these antiviral
      proteins. 

PMID- 24278313
TI  - Neural mechanism of facilitation system during physical fatigue.
AB  - An enhanced facilitation system caused by motivational input plays an important
      role in supporting performance during physical fatigue. We tried to clarify the
      neural mechanisms of the facilitation system during physical fatigue using
      magnetoencephalography (MEG) and a classical conditioning technique. Twelve right
      handed volunteers participated in this study. Participants underwent MEG
      recording during the imagery of maximum grips of the right hand guided by
      metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials
      were performed for 10 min; the metronome sounds were started 5 min after the
      beginning of the handgrip trials. The metronome sounds were used as conditioned
      stimuli and maximum handgrip trials as unconditioned stimuli. The next day, they
      were randomly assigned to two groups in a single-blinded, two-crossover fashion
      to undergo two types of MEG recordings, that is, for the control and motivation
      sessions, during the imagery of maximum grips of the right hand guided by
      metronome sounds for 10 min. The alpha-band event-related desynchronizations
      (ERDs) of the motivation session relative to the control session within the time
      windows of 500 to 700 and 800 to 900 ms after the onset of handgrip cue sounds
      were identified in the sensorimotor areas. In addition, the alpha-band ERD within
      the time window of 400 to 500 ms was identified in the right dorsolateral
      prefrontal cortex (Brodmann's area 46). The ERD level in the right dorsolateral
      prefrontal cortex was positively associated with that in the sensorimotor areas
      within the time window of 500 to 700 ms. These results suggest that the right
      dorsolateral prefrontal cortex is involved in the neural substrates of the
      facilitation system and activates the sensorimotor areas during physical fatigue.

PMID- 24278314
TI  - Constitutive function of the Ikaros transcription factor in primary leukemia
      cells from pediatric newly diagnosed high-risk and relapsed B-precursor ALL
      patients.
AB  - We examined the constitutive function of the Ikaros (IK) transcription factor in
      blast cells from pediatric B-precursor acute lymphoblastic leukemia (BPL)
      patients using multiple assay platforms and bioinformatics tools. We found no
      evidence of diminished IK expression or function for primary cells from high-risk
      BPL patients including a Philadelphia chromosome (Ph)(+) subset. Relapse clones
      as well as very aggressive in vivo clonogenic leukemic B-cell precursors isolated
      from spleens of xenografted NOD/SCID mice that developed overt leukemia after
      inoculation with primary leukemic cells of patients with BPL invariably and
      abundantly expressed intact IK protein. These results demonstrate that a lost or
      diminished IK function is not a characteristic feature of leukemic cells in Ph(+)
      or Ph(-) high-risk BPL. 

PMID- 24278316
TI  - Glycosylation of the Escherichia coli TibA self-associating autotransporter
      influences the conformation and the functionality of the protein.
AB  - The self-associating autotransporters (SAATs) are multifunctional secreted
      proteins of Escherichia coli, comprising the AIDA-I, TibA and Ag43 proteins. One
      of their characteristics is that they can be glycosylated. Glycosylation of AIDA
      I and Ag43 have been investigated, but not that of TibA. It is still not clear
      whether glycosylation of the SAATs affect their structure or their functionality.
      Therefore, we have looked at the effects of glycosylation on the TibA
      adhesin/invasin. TibA is glycosylated by TibC, a specific glycosyltransferase,
      and the two genes are encoded in an operon. In this study, we have found that the
      glycosylation of TibA is not limited to the extracellular functional domain, as
      previously observed with AIDA-I and Ag43. We have determined that unglycosylated
      TibA is not able to promote the adhesion of bacteria on cultured epithelial cell,
      even though it is still able to promote invasion, biofilm formation and
      autoaggregation of bacteria. We have purified the glycosylated and unglycosylated
      forms of TibA, and determined that TibA is less stable when not glycosylated. We
      finally observed that glycosylation affects the oligomerisation of TibA and that
      unglycosylated TibA is locked in a conformation that is not suited for adhesion.
      Our results suggest that the effect of glycosylation on the functionality of TibA
      is indirect. 

PMID- 24278315
TI  - Dynamics of bacterial communities during the ripening process of different
      Croatian cheese types derived from raw ewe's milk cheeses.
AB  - Microbial communities play an important role in cheese ripening and determine the
      flavor and taste of different cheese types to a large extent. However, under
      adverse conditions human pathogens may colonize cheese samples during ripening
      and may thus cause severe outbreaks of diarrhoea and other diseases. Therefore in
      the present study we investigated the bacterial community structure of three raw
      ewe's milk cheese types, which are produced without the application of starter
      cultures during ripening from two production sites based on fingerprinting in
      combination with next generation sequencing of 16S rRNA gene amplicons. Overall a
      surprisingly high diversity was found in the analyzed samples and overall up to
      213 OTU97 could be assigned. 20 of the major OTUs were present in all samples and
      include mostly lactic acid bacteria (LAB), mainly Lactococcus, and Enterococcus
      species. Abundance and diversity of these genera differed to a large extent
      between the 3 investigated cheese types and in response to the ripening process.
      Also a large number of non LAB genera could be identified based on phylogenetic
      alignments including mainly Enterobacteriaceae and Staphylococcacae. Some species
      belonging to these two families could be clearly assigned to species which are
      known as potential human pathogens like Staphylococcus saprophyticus or
      Salmonella spp. However, during cheese ripening their abundance was reduced. The
      bacterial genera, namely Lactobacillus, Streptococcus, Leuconostoc,
      Bifidobacterium, Brevibacterium, Corynebacterium, Clostridium, Staphylococcus,
      Thermoanerobacterium, E. coli, Hafnia, Pseudomonas, Janthinobacterium, Petrotoga,
      Kosmotoga, Megasphaera, Macrococcus, Mannheimia, Aerococcus, Vagococcus,
      Weissella and Pediococcus were identified at a relative low level and only in
      selected samples. Overall the microbial composition of the used milk and the
      management of the production units determined the bacterial community composition
      for all cheese types to a large extend, also at the late time points of cheese
      ripening. 

PMID- 24278317
TI  - Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that
      could be translated into specific patterns of brain atrophy. In the current study
      we have evaluated the relationship between different clinical expressions of
      classical ALS and measurements of brain cortical thickness. Cortical thickness
      analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients
      and 20 healthy controls. We explored three clinical traits of the disease,
      subdividing the patients into two groups for each of them: the bulbar or spinal
      onset, the higher or lower upper motor neuron burden, the faster or slower
      disease progression. We used both a whole brain vertex-wise analysis and a ROI
      analysis on primary motor areas. ALS patients showed cortical thinning in
      bilateral precentral gyrus, bilateral middle frontal gyrus, right superior
      temporal gyrus and right occipital cortex. ALS patients with higher upper motor
      neuron burden showed a significant cortical thinning in the right precentral
      gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS
      patients with spinal onset showed a significant cortical thinning in the right
      precentral gyrus and paracentral lobule, compared to healthy controls. ALS
      patients with faster progressive disease showed a significant cortical thinning
      in widespread bilateral frontal and temporal areas, including the bilateral
      precentral gyrus, compared to healthy controls. Focusing on the primary motor
      areas, the ROI analysis revealed that the mean cortical thickness values were
      significantly reduced in ALS patients with higher upper motor neuron burden,
      spinal onset and faster disease progression related to healthy controls. In
      conclusion, the thickness of primary motor cortex could be a useful surrogate
      marker of upper motor neuron involvement in ALS; also our results suggest that
      cortical thinning in motor and non motor areas seem to reflect the clinical
      heterogeneity of the disease. 

PMID- 24278318
TI  - Simulating the evolution of the human family: cooperative breeding increases in
      harsh environments.
AB  - Verbal and mathematical models that consider the costs and benefits of behavioral
      strategies have been useful in explaining animal behavior and are often used as
      the basis of evolutionary explanations of human behavior. In most cases, however,
      these models do not account for the effects that group structure and cultural
      traditions within a human population have on the costs and benefits of its
      members' decisions. Nor do they consider the likelihood that cultural as well as
      genetic traits will be subject to natural selection. In this paper, we present an
      agent-based model that incorporates some key aspects of human social structure
      and life history. We investigate the evolution of a population under conditions
      of different environmental harshness and in which selection can occur at the
      level of the group as well as the level of the individual. We focus on the
      evolution of a socially learned characteristic related to individuals'
      willingness to contribute to raising the offspring of others within their family
      group. We find that environmental harshness increases the frequency of
      individuals who make such contributions. However, under the conditions we
      stipulate, we also find that environmental variability can allow groups to
      survive with lower frequencies of helpers. The model presented here is inevitably
      a simplified representation of a human population, but it provides a basis for
      future modeling work toward evolutionary explanations of human behavior that
      consider the influence of both genetic and cultural transmission of behavior. 

PMID- 24278319
TI  - Malocclusion in early anatomically modern human: a reflection on the etiology of
      modern dental misalignment.
AB  - Malocclusions are common in modern populations. Yet, as the study of occlusion
      requires an almost intact dentition in both the maxilla and mandible, searching
      for the ultimate cause of malocclusion is a challenge: relatively little ancient
      material is available for research on occlusal states. The Qafzeh 9 skull is
      unique, as its preserved dentition allowed us to investigate the presence and
      manifestations of malocclusion. The aim of this study was thus to examine the
      occlusal condition in the Qafzeh 9 specimen in light of modern knowledge
      regarding the etiology of malocclusion. We revealed a pathologic occlusion in the
      Qafzeh 9 skull that probably originated in the early developmental stage of the
      dentition, and was aggravated by forces applied by mastication. When arch
      continuity is interrupted due to misalignment of teeth as in this case, force
      transmission is not equal on both sides, causing intra-arch outcomes such as
      mesialization of the teeth, midline deviation, rotations and the aggravation of
      crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the
      left; the incisors rotate mesio-buccally; the left segment is constricted; the
      left first molar is buccally positioned and the left premolars palatally tilted.
      The inter-arch evaluation revealed anterior cross bite with functional shift that
      might affect force transmission and bite force. In conclusion, the findings of
      the current study suggest that malocclusion of developmental origin was already
      present in early anatomically modern humans (AMH) (the present case being the
      oldest known case, dated to ca. 100,000 years); that there is no basis to the
      notion that early AMH had a better adjustment between teeth and jaw size; and
      that jaw-teeth size discrepancy could be found in prehistoric populations and is
      not a recent phenomenon. 

PMID- 24278320
TI  - Wild populations of Triatoma infestans are highly connected to intra-peridomestic
      conspecific populations in the Bolivian Andes.
AB  - Triatoma infestans, the major vector of Chagas disease south of the Amazon in
      South America, has a large distribution of wild populations, contrary to what has
      previously been stated. These populations have been suspected of being the source
      of reinfestation of human habitats and could impede the full success of vector
      control campaigns. This study examined gene flow between intra-peridomestic
      populations and wild populations collected in the surround areas in three Andean
      localities in Bolivia. The populations were defined according to temporal,
      ecological, and spatial criteria. After DNA extraction from the legs of each
      insect, the samples were analyzed using seven microsatellite markers. First, the
      analysis of molecular variance (AMOVA) detected an absence of differentiation
      between wild and intra-peridomestic populations, although strong structuring was
      observed between the populations within each environment. Then for some
      populations, the Bayesian method of assignment to inferred populations showed
      very similar assignment patterns of the members of wild or intra-peridomestic
      populations in each locality. Finally, the detection of the first-generation
      migrants within the different populations provided evidence of insect
      displacement from the wild to the intra-peridomestic environment. This result
      indicates that, after control campaigns in the Andes, controlling this new
      paradigm of vector transmission risk stemming from the invasion of human habitats
      by wild populations of T. infestans requires long-term maintenance of public
      monitoring to keep the risk at a minimal level. Since wild populations of T.
      infestans have also been detected elsewhere in Argentina, Paraguay, and Chile,
      there is an urgent need to take these populations into account in future
      monitoring of Chagas disease transmission. 

PMID- 24278321
TI  - Stem cell antigen 1-positive mesenchymal cells are the origin of follicular cells
      during thyroid regeneration.
AB  - Many tissues are thought to contain adult stem/progenitor cells that are
      responsible for repair of the tissue where they reside upon damage and/or
      carcinogenesis, conditions when cellular homeostasis becomes uncontrolled. While
      the presence of stem/progenitor cells of the thyroid has been suggested, how
      these cells contribute to thyroid regeneration remains unclear. Here we show the
      origin of thyroid follicular cells and the process of their maturation to become
      follicular cells during regeneration. By using beta-galactosidase (beta-gal)
      reporter mice in conjunction with partial thyroidectomy as a model for thyroid
      regeneration, and bromodeoxyuridine (BrdU) long label-retaining cell analysis, we
      demonstrated that stem cell antigen 1 (Sca1) and BrdU-positive, but beta-gal and
      NKX2-1 negative cells were found in the non-follicular mesenchymal area 7 days
      after partial thyroidectomy. They temporarily co-expressed cytokeratin 14, and
      were observed in part of follicles by day 35 post-partial thyroidectomy. Sca1,
      BrdU, beta-gal, and NKX2-1-positive cells were found 120 days post-partial
      thyroidectomy. These results suggested that Sca1 and BrdU positive cells may
      participate in the formation of new thyroid follicles after partial
      thyroidectomy. The process of thyroid follicular cell regeneration was
      recapitulated in ex vivo thyroid slice collagen gel culture studies. These
      studies will facilitate research on thyroid stem/progenitor cells and their roles
      in thyroid diseases, particularly thyroid carcinomas. 

PMID- 24278322
TI  - Identification of methanogenic archaea in the hyporheic sediment of Sitka stream.
AB  - Methanogenic archaea produce methane as a metabolic product under anoxic
      conditions and they play a crucial role in the global methane cycle. In this
      study molecular diversity of methanogenic archaea in the hyporheic sediment of
      the lowland stream Sitka (Olomouc, Czech Republic) was analyzed by PCR
      amplification, cloning and sequencing analysis of the methyl coenzyme M reductase
      alpha subunit (mcrA) gene. Sequencing analysis of 60 clones revealed 24 different
      mcrA phylotypes from hyporheic sedimentary layers to a depth of 50 cm. Phylotypes
      were affiliated with Methanomicrobiales, Methanosarcinales and Methanobacteriales
      orders. Only one phylotype remains unclassified. The majority of the phylotypes
      showed higher affiliation with uncultured methanogens than with known
      methanogenic species. The presence of relatively rich assemblage of methanogenic
      archaea confirmed that methanogens may be an important component of hyporheic
      microbial communities and may affect CH4 cycling in rivers. 

PMID- 24278323
TI  - Loss of the cytoskeletal protein Pdlim7 predisposes mice to heart defects and
      hemostatic dysfunction.
AB  - The actin-associated protein Pdlim7 is essential for heart and fin development in
      zebrafish; however, the expression and function of this PDZ-LIM family member in
      the mammal has remained unclear. Here, we show that Pdlim7 predominantly
      localizes to actin-rich structures in mice including the heart, vascular smooth
      muscle, and platelets. To test the requirement for Pdlim7 in mammalian
      development and function, we analyzed a mouse strain with global genetic
      inactivation of Pdlim7. We demonstrate that Pdlim7 loss-of-function leads to
      significant postnatal mortality. Inactivation of Pdlim7 does not disrupt cardiac
      development, but causes mild cardiac dysfunction in adult mice. Adult Pdlim7(-/-)
      mice displayed increased mitral and tricuspid valve annulus to body weight
      ratios. These structural aberrations in Pdlim7(-/-) mice were supported by three
      dimensional reconstructions of adult cardiac valves, which revealed increased
      surface area to volume ratios for the mitral and tricuspid valve leaflets.
      Unexpectedly, we found that loss of Pdlim7 triggers systemic venous and arterial
      thrombosis, leading to significant mortality shortly after birth in Pdlim7(+/-)
      (11/60) and Pdlim7(-/-) (19/35) mice. In line with a prothrombotic phenotype,
      adult Pdlim7(-/-) mice exhibit dramatically decreased tail bleed times compared
      to controls. These findings reveal a novel and unexpected function for Pdlim7 in
      maintaining proper hemostasis in neonatal and adult mice.

PMID- 24278324
TI  - Prospective control in catching: the persistent Angle-of-approach effect in
      lateral interception.
AB  - In lateral interception tasks balls converging onto the same interception
      location via different trajectories give rise to systematic differences in the
      kinematics of hand movement. While it is generally accepted that this angle-of
      approach effect reflects the prospective (on-line) control of movement,
      controversy exists with respect to the information used to guide the hand to the
      future interception location. Based on the pattern of errors observed in a task
      requiring visual extrapolation of line segments to their intersection with a
      second line, angle-of-approach effects in lateral interception have been argued
      to result from perceptual biases in the detection of information about the ball's
      future passing distance along the axis of hand movement. Here we demonstrate that
      this account does not hold under experimental scrutiny: The angle-of-approach
      effect still emerged when participants intercepted balls moving along
      trajectories characterized by a zero perceptual bias with respect to the ball's
      future arrival position (Experiment 4). Designing and validating such bias
      controlled trajectories were done using the line-intersection extrapolation task
      (Experiments 2 and 3). The experimental set-up used in the present series of
      experiments was first validated for the lateral interception and the line
      intersection extrapolation tasks: In Experiment 1 we used rectilinear ball
      trajectories to replicate the angle-of-approach effect in lateral interception of
      virtual balls. Using line segments extracted from these rectilinear ball
      trajectories, in Experiment 2 we replicated the reported pattern of errors in the
      estimated locus of intersection with the axis of hand movement. We used these
      errors to develop a set of bias-free trajectories. Experiment 3 confirmed that
      the perceptual biases had been corrected for successfully. We discuss the
      implications on the information-based regulation of hand movement of our finding
      that the angle-of-approach effect in lateral interception cannot not explained by
      perceptual biases in information about the ball's future passing distance. 

PMID- 24278325
TI  - Distinct effects of alcohol consumption and smoking on genetic alterations in
      head and neck carcinoma.
AB  - BACKGROUND: Tobacco and alcohol consumption are risk factors for head and neck
      squamous cell carcinoma (HNSCC). Recently, whole-exome sequencing clarified that
      smoking increased TP53 and other mutations in HNSCC; however, the effects of
      alcohol consumption on these genetic alterations remain unknown. We explored the
      association between alcohol consumption and somatic copy-number alterations
      (SCNAs) across the whole genome in human papillomavirus (HPV)-negative HNSCCs,
      and compared with the effects of smoking on genetic alterations. METHODS: SCNA
      and TP53 mutations in tumor samples were examined by high-resolution comparative
      genomic hybridization microarray 180K and by direct sequencing, respectively, and
      statistically analyzed for associations with alcohol consumption and smoking
      during the 20 years preceding diagnosis of HNSCC. Probes with a corrected p-value
      (=q-value) less than 0.05 and fold change greater than 1.2 or less than -1.2 were
      considered statistically significant. RESULTS: A total of 248 patients with HNSCC
      were enrolled. In the HPV-negative patients (n=221), heavy alcohol consumption
      was significantly associated with SCNAs of oncogenes/oncosuppressors that were
      previously reported to occur frequently in HNSCCs: CDKN2A (q=0.005), FHIT
      (q=0.005), 11q13 region including CCND1, FADD and CTTN (q=0.005), ERBB2 (HER2)
      (q=0.009), 3q25-qter including CCNL1, TP63, DCUN1D1 and PIK3CA (q=0.014), and
      CSMD1 (q=0.019). But, TP53 mutations were not affected. In contrast, smoking was
      associated with increased risk of TP53 mutations, but did not induce any
      significant SCNAs of oncogenes/oncosuppressors. CONCLUSION: These results suggest
      that both alcohol consumption and smoking had distinct effects on genetic
      alterations in HNSCCs. Heavy alcohol consumption may trigger previously known and
      unknown SCNAs, but may not induce TP53 mutation. In contrast, smoking may induce
      TP53 mutation, but may not trigger any SCNAs.

PMID- 24278326
TI  - Development and preliminary verification of a Mandarin-based hearing-aid fitting
      strategy.
AB  - OBJECTIVE: The purpose of this study was to design and to verify a new hearing
      aid fitting strategy (Aescu HRL-1) based on the acoustic features of Mandarin.
      The subjective and objective outcomes were compared to those fitted with NAL-NL1
      (National Acoustic Laboratory Non-Linear, version1) in Mandarin-speaking hearing
      aid users. DESIGN: Fifteen subjects with sensorineural hearing loss participated
      in this preliminary study. Each subject wore a pair of four-channel hearing aids
      fitted with the Aescu HRL-1 and NAL-NL1 prescriptions alternatively for 1 month.
      Objective and subjective tests including the Mandarin Monosyllable Recognition
      Test (MMRT), Mandarin Hearing in Noise Test (MHINT), International Outcome
      Inventory for Hearing Aids (IOI-HA), and a sound-quality questionnaire were used
      to evaluate the performance of the two prescriptions. RESULTS: The mean MMRT
      scores were 79.9% and 81.1% for NAL-NL1 and Aescu HRL-1 respectively. They are
      not statistically different. The corresponding MHINT signal-to-noise ratios were
      0.87 and 0.85 dB, also, no significant difference was found between these two
      strategies. However, in subjective questionnaires, overall, the sound-quality and
      IOI-HA scores were higher for Aescu HRL-1. CONCLUSIONS: The speech recognition
      performance based on Aescu HRL-1 is as good as that of NAL-NL1 for Mandarin
      speaking hearing-aid users. Moreover, the subjects generally responded that Aescu
      HRL-1 provides a more natural, richer, and better sound quality than does NAL
      NL1.

PMID- 24278327
TI  - Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510
      model of tauopathy.
AB  - Neurofibrillary tangles (NFTs) of tau are one of the defining hallmarks of
      Alzheimer's disease (AD), and are closely associated with neuronal degeneration.
      Although it has been suggested that calcium dysregulation is important to AD
      pathogenesis, few studies have probed the link between calcium homeostasis,
      synapse loss and pathological changes in tau. Here we test the hypothesis that
      pathological changes in tau are associated with changes in calcium by utilizing
      in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology
      due to over-expression of human mutant P301L tau. We observe prominent dendritic
      spine loss without disruptions in calcium homeostasis, indicating that tangles do
      not disrupt this fundamental feature of neuronal health, and that tau likely
      induces spine loss in a calcium-independent manner. 

PMID- 24278328
TI  - Enrichment and genome sequence of the group I.1a ammonia-oxidizing Archaeon "Ca.
      Nitrosotenuis uzonensis" representing a clade globally distributed in thermal
      habitats.
AB  - The discovery of ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota and
      the high abundance of archaeal ammonia monooxygenase subunit A encoding gene
      sequences in many environments have extended our perception of nitrifying
      microbial communities. Moreover, AOA are the only aerobic ammonia oxidizers known
      to be active in geothermal environments. Molecular data indicate that in many
      globally distributed terrestrial high-temperature habits a thaumarchaeotal
      lineage within the Nitrosopumilus cluster (also called "marine" group I.1a)
      thrives, but these microbes have neither been isolated from these systems nor
      functionally characterized in situ yet. In this study, we report on the
      enrichment and genomic characterization of a representative of this lineage from
      a thermal spring in Kamchatka. This thaumarchaeote, provisionally classified as
      "Candidatus Nitrosotenuis uzonensis", is a moderately thermophilic, non
      halophilic, chemolithoautotrophic ammonia oxidizer. The nearly complete genome
      sequence (assembled into a single scaffold) of this AOA confirmed the presence of
      the typical thaumarchaeotal pathways for ammonia oxidation and carbon fixation,
      and indicated its ability to produce coenzyme F420 and to chemotactically react
      to its environment. Interestingly, like members of the genus Nitrosoarchaeum,
      "Candidatus N. uzonensis" also possesses a putative artubulin-encoding gene.
      Genome comparisons to related AOA with available genome sequences confirmed that
      the newly cultured AOA has an average nucleotide identity far below the species
      threshold and revealed a substantial degree of genomic plasticity with unique
      genomic regions in "Ca. N. uzonensis", which potentially include genetic
      determinants of ecological niche differentiation. 

PMID- 24278329
TI  - Molecular analysis of bacterial communities and detection of potential pathogens
      in a recirculating aquaculture system for Scophthalmus maximus and Solea
      senegalensis.
AB  - The present study combined a DGGE and barcoded 16S rRNA pyrosequencing approach
      to assess bacterial composition in the water of a recirculating aquaculture
      system (RAS) with a shallow raceway system (SRS) for turbot (Scophthalmus
      maximus) and sole (Solea senegalensis). Barcoded pyrosequencing results were also
      used to determine the potential pathogen load in the RAS studied. Samples were
      collected from the water supply pipeline (Sup), fish production tanks (Pro),
      sedimentation filter (Sed), biofilter tank (Bio), and protein skimmer (Ozo; also
      used as an ozone reaction chamber) of twin RAS operating in parallel (one for
      each fish species). Our results revealed pronounced differences in bacterial
      community composition between turbot and sole RAS, suggesting that in the systems
      studied there is a strong species-specific effect on water bacterial communities.
      Proteobacteria was the most abundant phylum in the water supply and all RAS
      compartments. Other important taxonomic groups included the phylum Bacteriodetes.
      The saltwater supplied displayed a markedly lower richness and appeared to have
      very little influence on bacterial composition. The following potentially
      pathogenic species were detected: Photobacterium damselae in turbot (all
      compartments), Tenacibaculum discolor in turbot and sole (all compartments),
      Tenacibaculum soleae in turbot (all compartments) and sole (Pro, Sed and Bio),
      and Serratia marcescens in turbot (Sup, Sed, Bio and Ozo) and sole (only Sed)
      RAS. Despite the presence of these pathogens, no symptomatic fish were observed.
      Although we were able to identify potential pathogens, this approach should be
      employed with caution when monitoring aquaculture systems, as the required
      phylogenetic resolution for reliable identification of pathogens may not always
      be possible to achieve when employing 16S rRNA gene fragments. 

PMID- 24278330
TI  - HDAC4 does not act as a protein deacetylase in the postnatal murine brain in
      vivo.
AB  - Reversible protein acetylation provides a central mechanism for controlling gene
      expression and cellular signaling events. It is governed by the antagonistic
      commitment of two enzymes families: the histone acetyltransferases (HATs) and the
      histone deacetylases (HDACs). HDAC4, like its class IIa counterparts, is a potent
      transcriptional repressor through interactions with tissue specific transcription
      factors via its N-terminal domain. Whilst the lysine deacetylase activity of the
      class IIa HDACs is much less potent than that of the class I enzymes, HDAC4 has
      been reported to influence protein deacetylation through its interaction with
      HDAC3. To investigate the influence of HDAC4 on protein acetylation we employed
      the immunoaffinity-based AcetylScan proteomic method. We identified many proteins
      known to be modified by acetylation, but found that the absence of HDAC4 had no
      effect on the acetylation profile of the murine neonate brain. This is consistent
      with the biochemical data suggesting that HDAC4 may not function as a lysine
      deacetylase, but these in vivo data do not support the previous report showing
      that the enzymatic activity of HDAC3 might be modified by its interaction with
      HDAC4. To complement this work, we used Affymetrix arrays to investigate the
      effect of HDAC4 knock-out on the transcriptional profile of the postnatal murine
      brain. There was no effect on global transcription, consistent with the absence
      of a differential histone acetylation profile. Validation of the array data by
      Taq-man qPCR indicated that only protamine 1 and Igfbp6 mRNA levels were
      increased by more than one-fold and only Calml4 was decreased. The lack of a
      major effect on the transcriptional profile is consistent with the cytoplasmic
      location of HDAC4 in the P3 murine brain. 

PMID- 24278331
TI  - Resveratrol attenuates CoCl2-induced cochlear hair cell damage through
      upregulation of Sirtuin1 and NF-kappaB deacetylation.
AB  - The goals of this study were to investigate the effects of hypoxia on cochlear
      hair cell damage, and to explore the role of sirtuin1 in hypoxia-induced hair
      cell damage. Cochlear organotypic cultures from postnatal day 4 rats were used in
      this study. Hypoxia was induced by treating cochlear explants with CoCl2.
      Cochlear cultures were treated with CoCl2 alone or in combination with the
      sirtuin1 activator resveratrol and the sirtuin1 inhibitor sirtinol. Hair cell
      damage was identified by phalloidin staining and imaged using scanning electron
      microscopy. RT-PCR and Western blot analyses were used to detect the expression
      of sirtuin1 and acetylated nuclear factor-kappaB (NF-kappaB). Low concentrations
      of CoCl2 (100-200 MUM) did not cause an obvious change in the number and
      morphology of hair cells, whereas higher concentrations of CoCl2 (300-400 MUM)
      induced swelling of hair cells, accompanied by cell loss. Increased sirtuin1
      expression was induced by CoCl2 at 100 to 200 MUM, but not at 400 MUM. NF-kappaB
      acetylation was significantly increased in explants treated with 400 MUM CoCl2.
      Pretreatment with resveratrol prevented CoCl2-induced hair cell loss and
      acetylation of NF-kappaB. The protective effect of resveratrol was significantly
      reduced by sirtinol. CoCl2 induces hair cell damage in organotypic cochleae
      cultures. Resveratrol attenuates CoCl2-induced cochlear hair cell damage possibly
      via activation of sirtuin1, which deacetylates NF-kappaB. 

PMID- 24278332
TI  - Peritruncal coronary endothelial cells contribute to proximal coronary artery
      stems and their aortic orifices in the mouse heart.
AB  - Avian embryo experiments proved an ingrowth model for the coronary artery
      connections with the aorta. However, whether a similar mechanism applies to the
      mammalian heart still remains unclear. Here we analyzed how the main coronary
      arteries and their orifices form during murine heart development. Apelin (Apln)
      is expressed in coronary vascular endothelial cells including peritruncal
      endothelial cells. By immunostaining, however, we did not find Apln expression in
      endothelial cells of the aorta during the period of coronary vessel development
      (E10.5 to E15.5). As a result of this unique expression difference,
      Apln(CreERT2/+) genetically labels nascent coronary vessels forming on the heart,
      but not the aorta endothelium when pulse activated by tamoxifen injection at
      E10.5. This allowed us to define the temporal contribution of these distinct
      endothelial cell populations to formation of the murine coronary artery orifice.
      We found that the peritruncal endothelial cells were recruited to form the
      coronary artery orifices. These cells penetrate the wall of aorta and take up
      residence in the aortic sinus of valsalva. In conclusion, main coronary arteries
      and their orifices form through the recruitment and vascular remodeling of
      peritruncal endothelial cells in mammalian heart. 

PMID- 24278333
TI  - A novel widespread cryptic species and phylogeographic patterns within several
      giant clam species (Cardiidae: Tridacna) from the Indo-Pacific Ocean.
AB  - Giant clams (genus Tridacna) are iconic coral reef animals of the Indian and
      Pacific Oceans, easily recognizable by their massive shells and vibrantly colored
      mantle tissue. Most Tridacna species are listed by CITES and the IUCN Redlist, as
      their populations have been extensively harvested and depleted in many regions.
      Here, we survey Tridacna crocea and Tridacna maxima from the eastern Indian and
      western Pacific Oceans for mitochondrial (COI and 16S) and nuclear (ITS) sequence
      variation and consolidate these data with previous published results using
      phylogenetic analyses. We find deep intraspecific differentiation within both T.
      crocea and T. maxima. In T. crocea we describe a previously undocumented
      phylogeographic division to the east of Cenderawasih Bay (northwest New Guinea),
      whereas for T. maxima the previously described, distinctive lineage of
      Cenderawasih Bay can be seen to also typify western Pacific populations.
      Furthermore, we find an undescribed, monophyletic group that is evolutionarily
      distinct from named Tridacna species at both mitochondrial and nuclear loci. This
      cryptic taxon is geographically widespread with a range extent that minimally
      includes much of the central Indo-Pacific region. Our results reinforce the
      emerging paradigm that cryptic species are common among marine invertebrates,
      even for conspicuous and culturally significant taxa. Additionally, our results
      add to identified locations of genetic differentiation across the central Indo
      Pacific and highlight how phylogeographic patterns may differ even between
      closely related and co-distributed species. 

PMID- 24278334
TI  - rs929387 of GLI3 is involved in tooth agenesis in Chinese Han population.
AB  - Tooth agenesis is one of the most common anomalies of human dentition. Recent
      studies suggest that a number of genes are related to both syndromic and non
      syndromic forms of hypodontia. In a previous study, we observed that polymorphism
      in rs929387 of GLI3 might be associated with hypodontia in the Chinese Han
      population based on a limited population. To further confirm this observation, in
      this study, we employed 89 individuals diagnosed with sporadic non-syndromic
      oligodontia (40 males and 49 females) to investigate the relationship between
      polymorphism in rs929387 of GLI3 and tooth agenesis. These individuals were
      analyzed with 273 subjects (125 males and 148 females) diagnosed with non
      syndromic hypodontia and 200 healthy control subjects (100 males and 100
      females). DNA was obtained from whole blood or saliva samples and genotyping was
      performed by a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass
      Spectrometry (MALDI-TOF MS) method. Significant differences were observed in the
      allele and genotype frequencies of rs929387 of GLI3. Distributions of genotypes
      TT, TC and CC of rs929387 polymorphism were significantly different between the
      case group and the control group (P = 0.013) and C allelic frequency was higher
      in case group [P = 0.002, OR = 1.690, 95% CI (1.200-2.379)]. Additionally, our
      analysis shows that this difference is more pronounced when compared between the
      male case group and the male control group. The function study suggests that
      variation in GLI3 caused by rs929387 leads to a decrease in its transcriptional
      activity. These data demonstrated an association between rs929387 of GLI3 and non
      syndromic tooth agenesis in Chinese Han individuals. This information may provide
      further understanding of the molecular mechanisms of tooth agenesis. Furthermore,
      GLI3 can be regarded as a marker gene for the risk of tooth agenesis. 

PMID- 24278335
TI  - Phylogenomics and coalescent analyses resolve extant seed plant relationships.
AB  - The extant seed plants include more than 260,000 species that belong to five main
      lineages: angiosperms, conifers, cycads, Ginkgo, and gnetophytes. Despite
      tremendous effort using molecular data, phylogenetic relationships among these
      five lineages remain uncertain. Here, we provide the first broad coalescent-based
      species tree estimation of seed plants using genome-scale nuclear and plastid
      data By incorporating 305 nuclear genes and 47 plastid genes from 14 species, we
      identify that i) extant gymnosperms (i.e., conifers, cycads, Ginkgo, and
      gnetophytes) are monophyletic, ii) gnetophytes exhibit discordant placements
      within conifers between their nuclear and plastid genomes, and iii) cycads plus
      Ginkgo form a clade that is sister to all remaining extant gymnosperms. We
      additionally observe that the placement of Ginkgo inferred from coalescent
      analyses is congruent across different nucleotide rate partitions. In contrast,
      the standard concatenation method produces strongly supported, but incongruent
      placements of Ginkgo between slow- and fast-evolving sites. Specifically, fast
      evolving sites yield relationships in conflict with coalescent analyses. We
      hypothesize that this incongruence may be related to the way in which
      concatenation methods treat sites with elevated nucleotide substitution rates.
      More empirical and simulation investigations are needed to understand this
      potential weakness of concatenation methods. 

PMID- 24278336
TI  - Conservation in the context of climate change: practical guidelines for land
      protection at local scales.
AB  - Climate change will affect the composition of plant and animal communities in
      many habitats and geographic settings. This presents a dilemma for conservation
      programs--will the portfolio of protected lands we now have achieve a goal of
      conserving biodiversity in the future when the ecological communities occurring
      within them change? Climate change will significantly alter many plant
      communities, but the geophysical underpinnings of these landscapes, such as
      landform, elevation, soil, and geological properties, will largely remain the
      same. Studies show that extant landscapes with a diversity of geophysical
      characteristics support diverse plant and animal communities. Therefore,
      geophysically diverse landscapes will likely support diverse species assemblages
      in the future, although which species and communities will be present is not
      altogether clear. Following protocols advanced in studies spanning large regions,
      we developed a down-scaled, high spatial resolution measure of geophysical
      complexity based on Ecological Land Units (ELUs) and examined the relationship
      between plant species richness, ecological community richness, and ELU richness
      (number of different ELU types). We found that extant landscapes with high ELU
      richness had a greater variety of ecological community types and high species
      richness of trees, shrubs, and herbaceous plants. We developed a spatial
      representation of diverse ELU landscapes to inform local conservation
      practitioners, such as land trusts, of potential conservation targets that will
      likely support diverse faunas and floras despite the impact of climate change.

PMID- 24278337
TI  - Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL) located
      in a chromosomal region associated with cattle feed intake and gain.
AB  - A region on bovine chromosome 6 has been implicated in cattle birth weight,
      growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand
      dependent nuclear receptor corepressor-like protein (LCORL) are positional
      candidate genes within this region. Previously identified genetic markers in both
      genes were associated with average daily gain (ADG) and average daily feed intake
      (ADFI) in a crossbred population of beef steers. These markers were also
      associated with hot carcass weight, ribeye area and adjusted fat thickness
      suggesting that they may have a role in lean muscle growth and/or fat deposition.
      The purpose of this study was to determine whether the transcript abundance of
      either of these genes in cattle adipose and muscle tissue was associated with
      variation in feed intake and average daily gain phenotypes. Transcript abundance
      for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose
      only), cows and steers using real-time polymerase chain reaction. In the adipose
      tissue from cows and heifers, a negative correlation between LCORL transcript
      abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows,
      transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A
      positive correlation between LCORL transcript abundance from muscle tissue of
      steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of
      steers were investigated and were associated with ADFI (P = 0.01). These data
      support our earlier genetic associations with ADFI and ADG within this region and
      represent the potential for biological activity of these genes in the muscle and
      adipose tissues of beef cattle; however, they also suggest that sex, age and/or
      nutrition-specific interactions may affect the expression of NCAPG and LCORL in
      these tissues.

PMID- 24278338
TI  - Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating
      ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells.
AB  - BACKGROUND: Kaempferol has been proposed as a potential drug for cancer
      chemoprevention and treatment because it is a natural polyphenol contained in
      plant-based foods. Recent studies have demonstrated that kaempferol protects
      against cardiovascular disease and cancer. Based on this finding, we investigated
      the mechanisms by which kaempferol produces the anti-metastatic effect in human
      tongue squamous cell carcinoma SCC4 cells. METHODOLOGY/PRINCIPAL FINDINGS: In
      this study, we provided molecular evidence associated with the anti-metastatic
      effect of kaempferol by demonstrating a substantial suppression of SCC4 cell
      migration and invasion. This effect was associated with reduced expressions of
      MMP-2 and TIMP-2 mRNA and protein levels. Analysis of the transcriptional
      regulation indicated that kaempferol inhibited MMP-2 transcription by suppressing
      c-Jun activity. Kaempferol also produced an inhibitory effect on the
      phosphorylation of ERK1/2. CONCLUSIONS: These findings provide new insights into
      the molecular mechanisms involved in the anti-metastatic effect of kaempferol,
      and are valuable in the prevention of oral cancer metastasis.

PMID- 24278339
TI  - High theta and low alpha powers may be indicative of BCI-illiteracy in motor
      imagery.
AB  - In most brain computer interface (BCI) systems, some target users have
      significant difficulty in using BCI systems. Such target users are called 'BCI
      illiterate'. This phenomenon has been poorly investigated, and a clear
      understanding of the BCI-illiteracy mechanism or a solution to this problem has
      not been reported to date. In this study, we sought to demonstrate the
      neurophysiological differences between two groups (literate, illiterate) with a
      total of 52 subjects. We investigated recordings under non-task related state
      (NTS) which is collected during subject is relaxed with eyes open. We found that
      high theta and low alpha waves were noticeable in the BCI-illiterate relative to
      the BCI-literate people. Furthermore, these high theta and low alpha wave
      patterns were preserved across different mental states, such as NTS, resting
      before motor imagery (MI), and MI states, even though the spatial distribution of
      both BCI-illiterate and BCI-literate groups did not differ. From these findings,
      an effective strategy for pre-screening subjects for BCI illiteracy has been
      determined, and a performance factor that reflects potential user performance has
      been proposed using a simple combination of band powers. Our proposed performance
      factor gave an r = 0.59 (r(2) = 0.34) in a correlation analysis with BCI
      performance and yielded as much as r = 0.70 (r(2) = 0.50) when seven outliers
      were rejected during the evaluation of whole data (N = 61), including BCI
      competition datasets (N = 9). These findings may be directly applicable to online
      BCI systems.

PMID- 24278340
TI  - Comparison of soil respiration in typical conventional and new alternative cereal
      cropping systems on the North China plain.
AB  - We monitored soil respiration (Rs), soil temperature (T) and volumetric water
      content (VWC%) over four years in one typical conventional and four alternative
      cropping systems to understand Rs in different cropping systems with their
      respective management practices and environmental conditions. The control was
      conventional double-cropping system (winter wheat and summer maize in one year-
      Con.W/M). Four alternative cropping systems were designed with optimum water and
      N management, i.e. optimized winter wheat and summer maize (Opt.W/M), three
      harvests every two years (first year, winter wheat and summer maize or soybean;
      second year, fallow then spring maize--W/M-M and W/S-M), and single spring maize
      per year (M). Our results show that Rs responded mainly to the seasonal variation
      in T but was also greatly affected by straw return, root growth and soil moisture
      changes under different cropping systems. The mean seasonal CO2 emissions in
      Con.W/M were 16.8 and 15.1 Mg CO2 ha(-1) for summer maize and winter wheat,
      respectively, without straw return. They increased significantly by 26 and 35% in
      Opt.W/M, respectively, with straw return. Under the new alternative cropping
      systems with straw return, W/M-M showed similar Rs to Opt.W/M, but total CO2
      emissions of W/S-M decreased sharply relative to Opt.W/M when soybean was planted
      to replace summer maize. Total CO2 emissions expressed as the complete rotation
      cycles of W/S-M, Con.W/M and M treatments were not significantly different.
      Seasonal CO2 emissions were significantly correlated with the sum of carbon
      inputs of straw return from the previous season and the aboveground biomass in
      the current season, which explained 60% of seasonal CO2 emissions. T and VWC%
      explained up to 65% of Rs using the exponential-power and double exponential
      models, and the impacts of tillage and straw return must therefore be considered
      for accurate modeling of Rs in this geographical region.

PMID- 24278341
TI  - Endothelial relaxation mechanisms and oxidative stress are restored by
      atorvastatin therapy in ovariectomized rats.
AB  - The studies on hormone replacement therapy (HRT) in females with estrogen
      deficiency are not conclusive. Thus, non-estrogen therapies, such as atorvastatin
      (ATO), could be new strategies to substitute or complement HRT. This study
      evaluated the effects of ATO on mesenteric vascular bed (MVB) function from
      ovariectomized (OVX) female rats. Female rats were divided into control SHAM,
      OVX, and OVX treated with 17beta-estradiol (EST) or ATO groups. The MVB
      reactivity was determined in organ chambers, vascular oxidative stress by
      dihydroethidine staining, and the expression of target proteins by western blot.
      The reduction in acetylcholine-induced relaxation in OVX rats was restored by ATO
      or EST treatment. The endothelium-dependent nitric oxide (NO) component was
      reduced in OVX rats, whereas the endothelium-derived hyperpolarizing factor
      (EDHF) component or prostanoids were not altered in the MVBs. Endothelial
      dysfunction in OVX rats was associated with oxidative stress, an up-regulation of
      iNOS and NADPH oxidase expression and a down-regulation of eNOS expression.
      Treatment with ATO or EST improved the NO component of the relaxation and
      normalized oxidative stress and the expression of those signaling pathways
      enzymes. Thus, the protective effect of ATO on endothelial dysfunction caused by
      estrogen deficiency highlights a significant therapeutic benefit for statins
      independent of its effects on cholesterol, thus providing evidence that non
      estrogen therapy could be used for cardiovascular benefit in an estrogen
      deficient state, such as menopause. 

PMID- 24278342
TI  - Global distribution of Bartonella infections in domestic bovine and
      characterization of Bartonella bovis strains using multi-locus sequence typing.
AB  - Bartonella bovis is commonly detected in cattle. One B. bovis strain was recently
      isolated from a cow with endocarditis in the USA, suggesting its role as an
      animal pathogen. In the present study, we investigated bartonella infections in
      893 cattle from five countries (Kenya, Thailand, Japan, Georgia, and Guatemala)
      and 103 water buffaloes from Thailand to compare the prevalence of the infection
      among different regions and different bovid hosts. We developed a multi-locus
      sequence typing (MLST) scheme based on nine loci (16S rRNA, gltA, ftsZ, groEL,
      nuoG, ribC, rpoB, ssrA, and ITS) to compare genetic divergence of B. bovis
      strains, including 26 representatives from the present study and two previously
      described reference strains (one from French cows and another from a cow with
      endocarditis in the USA). Bartonella bacteria were cultured in 6.8% (7/103) of
      water buffaloes from Thailand; all were B. bovis. The prevalence of bartonella
      infections in cattle varied tremendously across the investigated regions. In
      Japan, Kenya, and the Mestia district of Georgia, cattle were free from the
      infection; in Thailand, Guatemala, and the Dusheti and Marneuli districts of
      Georgia, cattle were infected with prevalences of 10-90%. The Bartonella isolates
      from cattle belonged to three species: B. bovis (n=165), B. chomelii (n=9), and
      B. schoenbuchensis (n=1), with the latter two species found in Georgia only. MLST
      analysis suggested genetic variations among the 28 analyzed B. bovis strains,
      which fall into 3 lineages (I, II, and III). Lineages I and II were found in
      cattle while lineage III was restricted to water buffaloes. The majority of
      strains (17/28), together with the strain causing endocarditis in a cow in the
      USA, belonged to lineage I. Further investigations are needed to determine
      whether B. bovis causes disease in bovids. 

PMID- 24278343
TI  - The crustacean central nervous system in focus: subacute neurodegeneration
      induces a specific innate immune response.
AB  - To date nothing is known about the subacute phase of neurodegeneration following
      injury in invertebrates. Among few clues available are the results published by
      our group reporting hemocytes and activated glial cells at chronic and acute
      phases of the lesion. In vertebrates, glial activation and recruitment of
      immunological cells are crucial events during neurodegeneration. Here, we aimed
      to study the subacute stage of neurodegeneration in the crab Ucides cordatus,
      investigating the cellular/molecular strategy employed 48 hours following
      ablation of the protocerebral tract (PCT). We also explored the expression of
      nitric oxide (NO) and histamine in the PCT during this phase of
      neurodegeneration. Three immune cellular features which seem to characterize the
      subacute phase of neurodegeneration were revealed by: 1) the recruitment of
      granulocytes and secondarily of hyalinocytes to the lesion site (inducible NO
      synthase- and histamine-positive cells); 2) the attraction of a larger number of
      cells than observed in the acute phase; 3) the presence of activated glial cells
      as shown by the round shaped nuclei and increased expression of glial fibrillary
      acidic protein. We suggest that molecules released from granulocytes in the acute
      phase attract the hyalinocytes thus moving the degeneration process to the
      subacute phase. The importance of our study resides in the characterization of
      cellular and biochemical strategies peculiar to the subacute stage of the
      neurodegeneration in invertebrates. Such events are worth studying in crustaceans
      because in invertebrates this issue may be addressed with less interference from
      complex strategies resulting from the acquired immune system. 

PMID- 24278344
TI  - Osmostress-induced cell volume loss delays yeast Hog1 signaling by limiting
      diffusion processes and by Hog1-specific effects.
AB  - Signal transmission progresses via a series of transient protein-protein
      interactions and protein movements, which require diffusion within a cell packed
      with different molecules. Yeast Hog1, the effector protein kinase of the High
      Osmolarity Glycerol pathway, translocates transiently from the cytosol to the
      nucleus during adaptation to high external osmolarity. We followed the dynamics
      of osmostress-induced cell volume loss and Hog1 nuclear accumulation upon
      exposure of cells to different NaCl concentrations. While Hog1 nuclear
      accumulation peaked within five minutes following mild osmotic shock it was
      delayed up to six-fold under severe stress. The timing of Hog1 nuclear
      accumulation correlated with the degree of cell volume loss and the cells
      capacity to recover. Also the nuclear translocation of Msn2, the transcription
      factor of the general stress response pathway, is delayed upon severe osmotic
      stress suggesting a general phenomenon. We show by direct measurements that the
      general diffusion rate of Hog1 in the cytoplasm as well as its rate of nuclear
      transport are dramatically reduced following severe volume reduction. However,
      neither Hog1 phosphorylation nor Msn2 nuclear translocation were as much delayed
      as Hog1 nuclear translocation. Our data provide direct evidence that signaling
      slows down during cell volume compression, probably as a consequence of molecular
      crowding. Hence one purpose of osmotic adaptation is to restore optimal diffusion
      rates for biochemical and cell biological processes. In addition, there may be
      mechanisms slowing down especially Hog1 nuclear translocation under severe stress
      in order to prioritize Hog1 cytosolic targets. 

PMID- 24278345
TI  - Nanomechanics of the endothelial glycocalyx in experimental sepsis.
AB  - The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal
      side of the endothelium, regulates vascular adhesiveness and permeability.
      Although central to the pathophysiology of vascular barrier dysfunction in
      sepsis, glycocalyx damage has been generally understudied, in part because of the
      aberrancy of in vitro preparations and its degradation during tissue handling.
      The aim of this study was to analyze inflammation-induced damage of the eGC on
      living endothelial cells by atomic-force microscopy (AFM) nanoindentation
      technique. AFM revealed the existence of a mature eGC on the luminal endothelial
      surface of freshly isolated rodent aorta preparations ex vivo, as well as on
      cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM
      detected a marked reduction in glycocalyx thickness (266 +/- 12 vs. 137 +/- 17
      nm, P<0.0001) and stiffness (0.34 +/- 0.03 vs. 0.21 +/- 0.01 pN/mn, P<0.0001) in
      septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to
      controls. Corresponding in vitro experiments revealed that sepsis-associated
      mediators, such as thrombin, LPS or Tumor Necrosis Factor-alpha alone were
      sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (
      20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel
      approach to uncover mechanisms involved in deterioration and refurbishment of the
      eGC in sepsis. 

PMID- 24278346
TI  - Investigations on the Tobacco Necrosis Virus D p60 replicase protein.
AB  - Tobacco Necrosis Virus D (TNV-D), in the genus Betanecrovirus (family
      Tombusviridae), possesses a single-stranded, positive-sense RNA genome containing
      six open reading frames (ORFs). Two 5'-proximal ORFs (1 and 2) encode overlapping
      polypeptides of 22 and 82 kDa (p22 and p82, respectively) which are both required
      for replication. The p22 auxiliary protein contains no replication motifs but the
      C-terminal region, downstream of a leaky stop codon, encodes a 60 kDa polypeptide
      (p60) which contains conserved RNA-dependent RNA polymerase (RdRP) motifs. Here
      we have expressed and purified recombinant p60 and show that in vitro it binds
      and efficiently synthesises both TNV-D RNA and Satellite tobacco necrosis virus C
      RNA. Alanine scanning mutagenesis of conserved amino acids in characteristic
      motifs in p60 revealed that some mutations significantly reduced RNA synthesis
      but mutating the second asparagine residue in the conserved GDD box was lethal.
      The effects of mutating identical amino acids in p60 on virus replication in vivo
      were examined in Nicotiana benthamiana plants following infection with RNA
      transcribed from wild type (wt) and mutant constructs. In inoculated leaves the
      behaviour of the mutants paralleled the in vitro data but systemic infection was
      precluded in all but one mutant which had reverted to wt. This study is the first
      to demonstrate the nucleic acid-binding and synthetic capabilities of a
      betanecrovirus polymerase. 

PMID- 24278349
TI  - Functional diversification within a predatory species flock.
AB  - Ecological speciation is well-known from adaptive radiations in cichlid fishes
      inhabiting lentic ecosystems throughout the African rift valley and Central
      America. Here, we investigate the ecological and morphological diversification of
      a recently discovered lotic predatory Neotropical cichlid species flock in
      subtropical South America. We document morphological and functional
      diversification using geometric morphometrics, stable C and N isotopes, stomach
      contents and character evolution. This species flock displays species-specific
      diets and skull and pharyngeal jaw morphology. Moreover, this lineage appears to
      have independently evolved away from piscivory multiple times and derived forms
      are highly specialized morphologically and functionally relative to ancestral
      states. Ecological speciation played a fundamental role in this radiation and our
      data reveal novel conditions of ecological speciation including a species flock
      that evolved: 1) in a piscivorous lineage, 2) under lotic conditions and 3) with
      pronounced morphological novelties, including hypertrophied lips that appear to
      have evolved rapidly. 

PMID- 24278348
TI  - Human serum albumin and p53-activating peptide fusion protein is able to promote
      apoptosis and deliver fatty acid-modified molecules.
AB  - Therapeutic peptides offer a high degree of specificity, potency, and low
      toxicity; making them promising candidates for cancer therapy. Despite these
      advantages, a number of hurdles, such as poor serum stability and inefficient
      cellular penetration, must be overcome. Fusing a therapeutic peptide to human
      serum albumin (HSA) is a common approach to extend the serum stability of a
      peptide that binds to extracellular receptors. However, no study has shown that
      this approach can be applied to target intracellular proteins. Here we
      demonstrate the feasibility of using a recombinant human serum albumin (rHSA)
      fusion protein to simultaneously deliver two types of molecules: a peptide
      capable of binding an intracellular target, as well as fatty acid (FA)-modified
      FITC (FA-FITC). Two peptides reported to disrupt the intracellular p53 and
      MDM2/MDMX interaction were fused to the C-terminal of HSA. Cellular and
      biochemical studies indicate that rHSA fusion proteins were efficiently taken up
      by SJSA-1 cells and retained MDM2- and MDMX-binding activity. By inducing the
      accumulation of p53, both fusion proteins promoted efficient cytotoxicity in SJSA
      1 cells via caspase activation. Long chain fatty acid (LCFA) transportation is an
      essential endogenous function of HSA. This study also demonstrates that rHSA
      fusion proteins formed highly stable complexes with FA-FITC via non-covalent
      interactions. FA-FITC complexed with HSA could be internalized efficiently and
      rHSA-P53i and rHSA-PMI retained apoptotic activity as complex components. It is
      expected that such an approach can ultimately be used to facilitate intracellular
      delivery of two anticancer therapeutics, each with distinct but complimentary
      mechanisms, to achieve synergistic efficacy. 

PMID- 24278347
TI  - A broad phenotypic screen identifies novel phenotypes driven by a single mutant
      allele in Huntington's disease CAG knock-in mice.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding
      huntingtin. The disease has an insidious course, typically progressing over 10-15
      years until death. Currently there is no effective disease-modifying therapy. To
      better understand the HD pathogenic process we have developed genetic HTT CAG
      knock-in mouse models that accurately recapitulate the HD mutation in man. Here,
      we describe results of a broad, standardized phenotypic screen in 10-46 week old
      heterozygous HdhQ111 knock-in mice, probing a wide range of physiological
      systems. The results of this screen revealed a number of behavioral abnormalities
      in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning
      and coordination deficits, and impaired olfactory discrimination. The screen also
      provided evidence supporting subtle cardiovascular, lung, and plasma metabolite
      alterations. Importantly, our results reveal that a single mutant HTT allele in
      the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent
      with a dominant disease process in patients. These data provide a starting point
      for further investigation of several organ systems in HD, for the dissection of
      underlying pathogenic mechanisms and for the identification of reliable
      phenotypic endpoints for therapeutic testing. 

PMID- 24278350
TI  - Tracing Arab-Islamic inheritance in Madagascar: study of the Y-chromosome and
      mitochondrial DNA in the Antemoro.
AB  - Madagascar is located at the crossroads of the Asian and African worlds and is
      therefore of particular interest for studies on human population migration.
      Within the large human diversity of the Great Island, we focused our study on a
      particular ethnic group, the Antemoro. Their culture presents an important Arab
      Islamic influence, but the question of an Arab biological inheritance remains
      unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this
      ethnic group. Although the majority of Antemoro genetic ancestry comes from sub
      Saharan African and Southeast Asian gene pools, we observed in their paternal
      lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins.
      This inheritance was restricted to some Antemoro sub-groups. Statistical analyses
      tended to confirm significant Middle Eastern genetic contribution. This study
      gives a new perspective to the large human genetic diversity in Madagascar. 

PMID- 24278351
TI  - Implication of lateral genetic transfer in the emergence of Aeromonas hydrophila
      isolates of epidemic outbreaks in channel catfish.
AB  - To investigate the molecular basis of the emergence of Aeromonas hydrophila
      responsible for an epidemic outbreak of motile aeromonad septicemia of catfish in
      the Southeastern United States, we sequenced 11 A. hydrophila isolates that
      includes five reference and six recent epidemic isolates. Comparative genomics
      revealed that recent epidemic A. hydrophila isolates are highly clonal, whereas
      reference isolates are greatly diverse. We identified 55 epidemic-associated
      genetic regions with 313 predicted genes that are present in epidemic isolates
      but absent from reference isolates and 35% of these regions are located within
      genomic islands, suggesting their acquisition through lateral gene transfer. The
      epidemic-associated regions encode predicted prophage elements, pathogenicity
      islands, metabolic islands, fitness islands and genes of unknown functions, and
      34 of the genes encoded in these regions were predicted as virulence factors. We
      found two pilus biogenesis gene clusters encoded within predicted pathogenicity
      islands. A functional metabolic island that encodes a complete pathway for myo
      inositol catabolism was evident by the ability of epidemic A. hydrophila isolates
      to use myo-inositol as a sole carbon source. Testing of A. hydrophila field
      isolates found a consistent correlation between myo-inositol utilization as a
      sole carbon source and the presence of an epidemic-specific genetic marker. All
      epidemic isolates and one reference isolate shared a novel O-antigen cluster.
      Altogether we identified four different O-antigen biosynthesis gene clusters
      within the 11 sequenced A. hydrophila genomes. Our study reveals new insights
      into the evolutionary changes that have resulted in the emergence of recent
      epidemic A. hydrophila strains. 

PMID- 24278352
TI  - Role of cross-cleft contacts in NMDA receptor gating.
AB  - In response to brief glutamate exposure, NMDA receptors produce excitatory
      currents that have sub-maximal amplitudes and characteristically slow kinetics.
      The activation sequence starts when glutamate binds to residues located on the
      upper lobe of extracellularly located ligand-binding domains (LBDs) and then
      contacts lower lobe residues to bridge the cleft between the two hinged lobes.
      This event stabilizes a narrow-cleft LBD conformation and may facilitate
      subsequent inter-lobe contacts that further stabilize the closed cleft. Agonist
      efficacy has been traced to the degree of agonist-induced cleft-closure and may
      also depend on the stability of the closed-cleft conformation. To investigate how
      cross-cleft contacts contribute to the amplitude and kinetics of NMDA receptor
      response, we examined the activation reaction of GluN1/GluN2A receptors that had
      single-residue substitutions at the interface between LBD lobes. We found that
      side-chain truncations at residues of putative contact between lobes increased
      glutamate efficacy through independent additive mechanisms in GluN1 and GluN2A
      subunits. In contrast, removing side-chain charge with isosteric substitutions at
      the same sites decreased glutamate efficacy. These results support the view that
      in GluN1/GluN2A receptors' natural interactions between residues on opposing
      sides of the ligand-binding cleft encode the stability of the glutamate-bound
      closed-cleft conformations and limit the degree of cleft closure, thus
      contributing to the sub-maximal response and emblematically slow NMDA receptor
      deactivation after brief stimulation. 

PMID- 24278353
TI  - Coastal fish assemblages reflect geological and oceanographic gradients within an
      Australian zootone.
AB  - Distributions of mobile animals have been shown to be heavily influenced by
      habitat and climate. We address the historical and contemporary context of fish
      habitats within a major zootone: the Recherche Archipelago, southern western
      Australia. Baited remote underwater video systems were set in nine habitat types
      within three regions to determine the species diversity and relative abundance of
      bony fishes, sharks and rays. Constrained ordinations and multivariate prediction
      and regression trees were used to examine the effects of gradients in longitude,
      depth, distance from islands and coast, and epibenthic habitat on fish assemblage
      composition. A total of 90 species from 43 families were recorded from a wide
      range of functional groups. Ordination accounted for 19% of the variation in the
      assemblage composition when constrained by spatial and epibenthic covariates, and
      identified redundancy in the use of distance from the nearest emergent island as
      a predictor. A spatial hierarchy of fourteen fish assemblages was identified
      using multivariate prediction and regression trees, with the primary split
      between assemblages on macroalgal reefs, and those on bare or sandy habitats
      supporting seagrass beds. The characterisation of indicator species for
      assemblages within the hierarchy revealed important faunal break in fish
      assemblages at 122.30 East at Cape Le Grand and subtle niche partitioning amongst
      species within the labrids and monacanthids. For example, some species of
      monacanthids were habitat specialists and predominantly found on seagrass
      (Acanthaluteres vittiger, Scobinichthys granulatus), reef (Meuschenia galii,
      Meuschenia hippocrepis) or sand habitats (Nelusetta ayraudi). Predatory fish that
      consume molluscs, crustaceans and cephalopods were dominant with evidence of
      habitat generalisation in reef species to cope with local disturbances by wave
      action. Niche separation within major genera, and a sub-regional faunal break,
      indicate future zootone mapping should recognise both cross-shelf and longshore
      environmental gradients. 

PMID- 24278354
TI  - Human umbilical mesenchymal stem cells-seeded bladder acellular matrix grafts for
      reconstruction of bladder defects in a canine model.
AB  - BACKGROUND: The goal of this study was to explore the feasibility of utilizing
      human umbilical mesenchymal stem cells (HUMSCs)-seeded Bladder acellular matrix
      graft (BAMG) for bladder reconstruction in a canine model. METHODOLOGY/PRINCIPAL
      FINDINGS: HUMSCs were isolated from newborn umbilical cords and identified by
      flow cytometry. Partial cystectomy was performed in the experimental and control
      group. Bladder defects were repaired with HUMSCs-BAMG in the experimental group
      and repaired with unseeded-BAMG in control group. The implanted grafts were
      harvested after surgery. H&E and immunohistochemistry staining were performed to
      evaluate the regeneration of the bladder defect. Primary cultured HUMSCs
      displayed typical fibroblast morphology with spindle-shaped. Flow cytometry
      indicated that these cells were positive for CD105 (97.3%) and CD44 (99%), but
      negative for CD34 (2.8%), CD31 (2.1%), and CD45 (1.7%). Immunohistochemistry
      staining showed that a multilayered urothelium and well-developed smooth muscle
      were observed at 12 weeks in experiment group. In contrast, multilayered
      urothelial tissues were also observed at 12 weeks in group B, but well-developed
      smooth muscle bundles were observed. CONCLUSIONS/SIGNIFICANCE: Our preliminary
      results demonstrate that UMSC-seeded BAMGs are superior to unseeded BAMGs to
      promote the regeneration of bladder defects. Our findings indicated that HUMSCs
      may be a potential cell source for bladder tissue engineering.

PMID- 24278355
TI  - Outcomes of middle cardiac vein arterialization via internal mammary/thoracic
      artery anastomosis.
AB  - OBJECTIVE: Cardiac vein arterialization is seldom applied for treating right
      coronary artery disease. This study aimed to improve outcomes of cardiac vein
      arterialization in a porcine model using intramammary artery anastomosis.
      METHODS: A chronic, stenotic coronary artery model was established in 12 of 14
      Chinese experimental miniature pigs of either sex, which were randomly divided
      into equal control (n =6) and experimental (n = 6) groups. In experimental
      animals, blood flow was reconstructed in the right coronary artery using
      intramammary artery. Arterialization involved dissection of right internal
      mammary artery from bifurcation to apex of thorax followed by end-to-side
      anastomosis of internal mammary artery and middle cardiac vein plus posterior
      descending branch of right coronary artery. Intraoperative heart rate was
      maintained at 110 beats/min. Graft flow assessment and echocardiography were
      performed when blood pressure and heart rate normalized. RESULTS: The
      experimental group had significantly higher mean endocardial and epicardial blood
      flow postoperatively than control group (mean endocardial blood flow: 0.37 vs.
      0.14 ml/(g*min), p<0.001; mean epicardial blood flow: 0.29 vs. 0.22, p = 0.014).
      Transmural blood flow was also higher in experimental group than in control group
      (0.33 vs. 0.19, p<0.001); ejection fraction increased from 0.46% at baseline to
      0.51% (p = 0.0038) at 6 hours postoperatively, and mean blood flow of internal
      mammary artery was 44.50, perfusion index 0.73 at postoperative 6 months, 43.33
      and 0.80 at 3 months. CONCLUSION: Successful cardiac vein arterialization via
      intramammary artery in a porcine model suggests that this may be a viable method
      for reconstructing blood flow in chronic, severe coronary artery disease.

PMID- 24278356
TI  - A new freshwater biodiversity indicator based on fish community assemblages.
AB  - Biodiversity has reached a critical state. In this context, stakeholders need
      indicators that both provide a synthetic view of the state of biodiversity and
      can be used as communication tools. Using river fishes as model, we developed
      community indicators that aim at integrating various components of biodiversity
      including interactions between species and ultimately the processes influencing
      ecosystem functions. We developed indices at the species level based on (i) the
      concept of specialization directly linked to the niche theory and (ii) the
      concept of originality measuring the overall degree of differences between a
      species and all other species in the same clade. Five major types of originality
      indices, based on phylogeny, habitat-linked and diet-linked morphology, life
      history traits, and ecological niche were analyzed. In a second step, we tested
      the relationship between all biodiversity indices and land use as a proxy of
      human pressures. Fish communities showed no significant temporal trend for most
      of these indices, but both originality indices based on diet- and habitat- linked
      morphology showed a significant increase through time. From a spatial point of
      view, all indices clearly singled out Corsica Island as having higher average
      originality and specialization. Finally, we observed that the originality index
      based on niche traits might be used as an informative biodiversity indicator
      because we showed it is sensitive to different land use classes along a landscape
      artificialization gradient. Moreover, its response remained unchanged over two
      other land use classifications at the global scale and also at the regional
      scale. 

PMID- 24278357
TI  - Pre-exposure of Mycobacterium tuberculosis-infected macrophages to crystalline
      silica impairs control of bacterial growth by deregulating the balance between
      apoptosis and necrosis.
AB  - Inhalation of crystalline silica (CS) particles increases the risk of pulmonary
      tuberculosis; however, the precise mechanism through which CS exposure
      facilitates Mycobacterium tuberculosis (Mtb) infection is unclear. We speculate
      that macrophage exposure to CS deregulates the cell death pathways that could
      explain, at least in part, the association observed between exposure to CS and
      pulmonary tuberculosis. We therefore established an in vitro model in which
      macrophages were exposed to CS and then infected with Mtb. Expression of surface
      markers was analyzed by flow cytometry, JNK1/2, ASK1, caspase 9, P-p38, Bcl-2 and
      Mcl-1 were analyzed by Western blot, and cytokines by ELISA. Our results show
      that exposure to CS limits macrophage ability to control Mtb growth. Moreover,
      this exposure reduced the expression of TLR2, Bcl-2 and Mcl-1, but increased that
      of JNK1 and ASK1 molecules in the macrophages. Finally, when the pre-exposed
      macrophages were infected with Mtb, the concentrations of TNFalpha, IL-1beta and
      caspase-9 expression increased. This pro-inflammatory profile of the macrophage
      unbalanced the apoptosis/necrosis pathway. Taken together, these data suggest
      that macrophages exposed to CS are sensitized to cell death by MAPK kinase
      dependent signaling pathway. Secretion of TNF-alpha and IL-1beta by Mtb-infected
      macrophages promotes necrosis, and this deregulation of cell death pathways may
      favor the release of viable bacilli, thus leading to the progression of
      tuberculosis. 

PMID- 24278358
TI  - Biopersistent granular dust and chronic obstructive pulmonary disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Applying a systematic review to identify studies eligible for meta
      analysis of the association between occupational exposure to inorganic dust and
      the development of chronic obstructive pulmonary disease (COPD), and conducting a
      meta-analysis. DATA SOURCES: Searches of PubMed and Embase for the time period
      1970-2010 yielded 257 cross-sectional and longitudinal studies on people exposed
      to inorganic dust at the workplace with data on lung function. These studies were
      independently abstracted and evaluated by two authors; any disagreement was
      resolved by a third reviewer. Of 55 publications accepted for meta-analysis, 27
      investigated the effects of occupational exposure to biopersistent granular dust
      (bg-dust). METHODS: A random effects meta-analysis allowed us to provide an
      estimate of the average exposure effect on spirometric parameters presented in
      forest plots. Between-study heterogeneity was assessed by using I(2) statistics,
      with I(2)>25% indicating significant heterogeneity. Publication bias was
      investigated by visual inspection of funnel plots. The influence of individual
      studies was assessed by dropping the respective study before pooling study
      specific estimates. RESULTS: The mean FEV1 of workers exposed to bg-dust was 160
      ml lower or 5.7% less than predicted compared to workers with no/low exposure.
      The risk of an obstructive airway disease--defined as FEV1/FVC < 70%--increased
      by 7% per 1 mg . m(-3) respirable bg-dust. CONCLUSION: Occupational inhalative
      exposure to bg-dust was associated with a statistically significant decreased
      FEV1 and FEV1/FVC revealing airway obstruction consistent with COPD.

PMID- 24278360
TI  - Causes and outcomes of acute liver failure in China.
AB  - OBJECTIVES: No extensive investigation has been performed and thus no
      representative data are available regarding acute liver failure (ALF) in China.
      This study aims to investigate the causes and outcomes of ALF in China and
      establish a prognostic model. METHODS: Patients diagnosed as ALF in seven
      hospitals in different areas of China from January 2007 to December 2012 were
      retrospectively selected. RESULTS: Of the 177 patients included in this study,
      112 (63.28%) eventually died. The common causes of ALF were drug toxicity
      (43.50%), indeterminate etiology (29.38%) and acute viral hepatitis (11.30%).
      Additionally, traditional Chinese herbs predominated in the causes of drug
      induced ALF (30/77). No patients in this study received liver transplantation. In
      the established model for predicting death in ALF, four variables were finally
      selected out, including age (P=0.01), the entry hepatic encephalopathy grade
      (P=0.04), international normalized ratio (P<0.01) and arterial blood ammonia
      (P=0.02). Using a threshold value of 0.5683, this model had a sensitivity of
      95.24% and a specificity of 91.30%. CONCLUSIONS: Traditional Chinese medicine was
      a major cause of ALF in China. The spontaneous mortality of ALF was high, whereas
      the rate of liver transplantation was significantly low. The established
      prognostic model of ALF had superior sensitivity and specificity.

PMID- 24278359
TI  - Detection of specific IgA antibodies against a novel deamidated 8-Mer gliadin
      peptide in blood plasma samples from celiac patients.
AB  - We studied whether celiac disease (CD) patients produce antibodies against a
      novel gliadin peptide specifically generated in the duodenum of CD patients by a
      previously described pattern of CD-specific duodenal proteases. Fingerprinting
      and ion-trap mass spectrometry of CD-specific duodenal gliadin-degrading protease
      pattern revealed a new 8-mer gliadin-derived peptide. An ELISA against synthetic
      deamidated 8-mer peptides (DGP 8-mer) was used to study the presence of IgA anti
      DGP 8-mer antibodies in plasma samples from 81 children (31 active CD patients
      (aCD), 17 CD patients on a gluten-free diet (GFD), 10 healthy controls (C) and 23
      patients with other gastrointestinal pathology (GP)) and 101 adults (16 aCD, 12
      GFD, 27 C and 46 GP-patients). Deamidation of the 8-mer peptide significantly
      increased the reactivity of the IgA antibodies from CD patients against the
      peptide. Significant IgA anti-DGP 8-mer antibodies levels were detected in 93.5%
      of aCD-, 11.8% of GFD- and 4.3% of GP-patients in children. In adults, antibodies
      were detected in 81.3% of aCD-patients and 8.3% of GFD-patients while were absent
      in 100% of C- and GP-patients. Duodenal CD-specific gliadin degrading proteases
      release an 8-mer gliadin peptide that once deamidated is an antigen for specific
      IgA antibodies in CD patients which may provide a new accurate diagnostic tool in
      CD. 

PMID- 24278361
TI  - Total serum IgE in a population-based study of Asian children in Taiwan:
      reference value and significance in the diagnosis of allergy.
AB  - BACKGROUND: Total serum immunoglobulin (IgE) test is usually performed to aid in
      the diagnosis of allergic diseases, but its reference values may vary among
      people of different ethnic backgrounds. OBJECTIVES: To establish reference values
      of total IgE in Asian children and to assess their significance in the diagnosis
      of atopy and allergic diseases. STUDY DESIGN: 1321 Asian children aged 5-18 years
      in the Prediction of Allergies in Taiwanese CHildren (PATCH) study, a population
      based cohort, were evaluated for total and specific IgE by ImmunoCAP and
      Phadiatop Infant, respectively. RESULTS: Male, atopy, allergic diseases, recent
      symptoms of upper respiratory infection, and lower FEV1/FVC, were associated with
      higher total IgE levels in univariate analyses. Multivariate analysis revealed
      that atopy was the single most important determinant explaining 66.1% of the
      variability of total IgE levels in this population. The area under the receiver
      operator characteristic (ROC) curve of total IgE for diagnosing atopy, asthma,
      rhinitis, and eczema were 0.92, 0.72, 0.70, and 0.70, respectively. The
      sensitivity, specificity, and positive and negative predictive values of total
      IgE at the optimal cutoff of 77.7 kU/L on the ROC curve for diagnosing atopy were
      82.3%, 87.1%, 89.5%, and 78.6%, respectively. The corresponding values using the
      upper 95% CI of total IgE (164.3 kU/L) in non-atopic children were 61.2%, 95.0%,
      94.3%, and 64.6%, respectively; whereas a customary cutoff (100 kU/L) provided
      accuracy between that of the aforementioned two cutoffs. Total IgE at the cutoff
      of 77.7 kU/L provided modest sensitivity and specificity (49.0%-78.3%) for
      diagnosing allergic diseases, but had high negative predictive values (84.2%
      97.9%). CONCLUSIONS: Total serum IgE discriminates Asian children with and
      without atopy independent of allergic symptoms, with an optimal cutoff of 77.7
      kU/L. The study confirms the insufficient diagnostic accuracy of total IgE alone
      to detect allergic diseases, but low total IgE levels may help exclude allergic
      diseases.

PMID- 24278362
TI  - Chemoresistance to concanamycin A1 in human oral squamous cell carcinoma is
      attenuated by an HDAC inhibitor partly via suppression of Bcl-2 expression.
AB  - V-ATPase is involved in the acidification of the microenvironment around/in solid
      tumors, such as oral squamous cell carcinoma (OSCC). V-ATPase is thought to
      induce tumor invasion and multi-drug resistance in several malignant tumors, and
      it also contributes to maintaining the intracellular pH under an acidic
      microenvironment by inducing proton extrusion into the extracellular medium.
      However, there is little information regarding the effects of V-ATPase inhibitors
      on OSCCs. In this study, the effects of a V-ATPase inhibitor, concanamycin A1
      (CMA), on the proliferation and apoptosis of OSCC were investigated in vitro. We
      used four OSCC cell lines, MISK81-5, SAS, HSC-4 and SQUU-B. Acridine orange
      staining revealed that the red fluorescence was reduced in all of the low
      concentration CMA-treated OSCC cells, indicating that the acidification of
      vesicular organelles in the OSCCs was prevented by the treatment with low
      concentration of CMA. CMA treatment induced apoptosis in MISK81-5, SAS and HSC-4
      cells, but not in SQUU-B cells. The p-p38 expression was not altered in CMA
      treated SQUU-B cells, but their levels were increased in the other cells. The
      Bax/Bcl-2 ratio in CMA-treated SQUU-B cells was dramatically decreased in
      comparison with that in the other cell lines treated with CMA. However, when the
      SQUU-B cells were treated with CMA and a histone deacetylase inhibitor,
      suberoylanilide hydroxamic acid (SAHA), the SQUU-B cells became more susceptible
      to the CMA-induced apoptosis. SAHA treatment led to a significantly decrease in
      the Bcl-2 expression in CMA-treated SQUU-B cells, resulting in a dramatically
      increased Bax/Bcl-2 ratio in comparison with that observed in the SQUU-B cells
      treated with CMA alone. These findings suggest that CMA could have an anti-tumor
      effect on OSCCs. In addition, combination of CMA with other agents, such as SAHA,
      could help improve the pro-apoptotic effects of CMA even in CMA-resistant OSCC
      cells. 

PMID- 24278363
TI  - Improvements of the surgical technique on the established mouse model of
      orthotopic single lung transplantation.
AB  - BACKGROUND: A wide range of knockout and transgenic murine models for the study
      of nonimmune and immune mechanisms in lung transplants are available nowadays,
      but the microsurgical techniques are difficult to learn. We describe methods to
      simplify techniques and facilitate learning. METHODS: Traditional procedures were
      implemented to perform lung transplants in 30 cases (group 1). Improved
      techniques which included cuff without tail, broadening of the cuff diameter for
      bronchus, establishment of one tunnel between three structures, innovative
      technology of the vascular anastomosis and placement of the chest tube post
      operation were used to perform lung transplants in 30 cases (group 2). RESULTS:
      The improved techniques considerably shorten operative times (96.75 +/- 6.16 min
      and 85.32 +/- 6.98 min in groups 1 and 2, respectively). The survival rates in
      the recipient animals were 86.7% and 96.7% in groups 1 and 2, respectively. Chest
      X-rays and macroscopic changes of transplanted recipients showed that grafts were
      well inflated on postoperative day 30. There was no significant difference of the
      arterial oxygen tension (PaO2) between two groups (115.9 +/- 7.11 mm Hg and 116.3
      +/- 6.87 mm Hg in groups 1 and 2, respectively). Histologically, no lung injury
      was seen in grafts. CONCLUSIONS: We described the modified procedures of
      orthotopic left lung transplants in mice, which could shorten operative time and
      increase survival rate.

PMID- 24278364
TI  - Feasibility of the use of combinatorial chemokine arrays to study blood and CSF
      in multiple sclerosis.
AB  - Meningeal inflammation, including the presence of semi-organized tertiary
      lymphoid tissue, has been associated with cortical pathology at autopsy in
      secondary progressive multiple sclerosis (SPMS). Accessible and robust
      biochemical markers of cortical inflammation for use in SPMS clinical trials are
      needed. Increased levels of chemokines in the cerebrospinal fluid (CSF) can
      report on inflammatory processes occurring in the cerebral cortex of MS patients.
      A multiplexed chemokine array that included BAFF, a high sensitivity CXCL13 assay
      and composite chemokine scores were developed to explore differences in lymphoid
      (CXCL12, CXCL13, CCL19 and CCL21) and inflammatory (CCL2, CXCL9, CXCL10 and
      CXCL11) chemokines in a small pilot study. Paired CSF and serum samples were
      obtained from healthy controls (n=12), relapsing-remitting MS (RRMS) (n=21) and
      SPMS (N=12). A subset of the RRMS patients (n = 9) was assessed upon disease
      exacerbation and 1 month later following iv methylprednisone. SPMS patients were
      sampled twice to ascertain stability. Both lymphoid and inflammatory chemokines
      were elevated in RRMS and SPMS with the highest levels found in the active RRMS
      group. Inflammatory and lymphoid chemokine signatures were defined and generally
      correlated with each other. This small exploratory clinical study shows the
      feasibility of measuring complex and potentially more robust chemokine signatures
      in the CSF of MS patients during clinical trials. No differences were found
      between stable RRMS and SPMS. Future trials with larger patient cohorts with this
      chemokine array are needed to further characterize the differences, or the lack
      thereof, between stable RRMS and SPMS.

PMID- 24278366
TI  - The Nogo-B-PirB axis controls macrophage-mediated vascular remodeling.
AB  - OBJECTIVE: Nogo-B mediates vascular protection and facilitates monocyte- and
      macrophage-dependent vascular remodeling. PirB is an alternate receptor for Nogo
      B, but a role for the Nogo-PirB axis within the vascular system has not been
      previously reported. We examined whether Nogo-B or PirB play a role in regulating
      macrophage-mediated vascular remodeling and hypothesized that endothelial Nogo-B
      regulates vein graft macrophage infiltration via its alternate receptor PirB.
      METHODS: Vein grafts were performed using Nogo and PirB wild type and knockout
      mice. Human vein grafts were similarly analyzed. The hindlimb ischemia model was
      performed in PirB wild type and knockout mice. Accompanying in vitro work
      included isolation of macrophages from PirB wild type and knockout mice. RESULTS:
      Increased Nogo-B and PirB mRNA transcripts and protein expression were observed
      within mouse and human vein grafts. Both Nogo knockout and PirB knockout vein
      grafts showed increased wall thickness and increased numbers of F4/80-positive
      macrophages. Macrophages derived from PirB knockout mice had increased adhesion
      to fibronectin, increased EC-specific binding, and increased numbers of mRNA
      transcripts of M2 markers as well as MMP3 and MMP9. PirB knockout vein grafts had
      increased active MMP9 compared to wild type vein grafts. PirB knockout mice had
      increased recovery from hindlimb ischemia and increased macrophage infiltration
      compared to wild type mice. CONCLUSIONS: Vein graft adaptation shows increased
      expression of both Nogo-B and PirB. Loss of PirB, or its endothelial ligand Nogo
      B, results in increased inflammatory cell infiltration and vein graft wall
      thickening. These findings suggest that PirB regulates macrophage activity in
      vein grafts and that Nogo-B in the vein graft limits macrophage infiltration and
      vein graft thickening. PirB may play a more general role in regulating macrophage
      responses to vascular injury. Macrophage inhibition via Nogo-PirB interactions
      may be an important mechanism regulating vein graft adaptation to the arterial
      circulation.

PMID- 24278367
TI  - River ecosystem response to prescribed vegetation burning on Blanket Peatland.
AB  - Catchment-scale land-use change is recognised as a major threat to aquatic
      biodiversity and ecosystem functioning globally. In the UK uplands rotational
      vegetation burning is practised widely to boost production of recreational game
      birds, and while some recent studies have suggested burning can alter river water
      quality there has been minimal attention paid to effects on aquatic biota. We
      studied ten rivers across the north of England between March 2010 and October
      2011, five of which drained burned catchments and five from unburned catchments.
      There were significant effects of burning, season and their interaction on river
      macroinvertebrate communities, with rivers draining burned catchments having
      significantly lower taxonomic richness and Simpson's diversity. ANOSIM revealed a
      significant effect of burning on macroinvertebrate community composition, with
      typically reduced Ephemeroptera abundance and diversity and greater abundance of
      Chironomidae and Nemouridae. Grazer and collector-gatherer feeding groups were
      also significantly less abundant in rivers draining burned catchments. These
      biotic changes were associated with lower pH and higher Si, Mn, Fe and Al in
      burned systems. Vegetation burning on peatland therefore has effects beyond the
      terrestrial part of the system where the management intervention is being
      practiced. Similar responses of river macroinvertebrate communities have been
      observed in peatlands disturbed by forestry activity across northern Europe.
      Finally we found river ecosystem changes similar to those observed in studies of
      wild and prescribed forest fires across North America and South Africa,
      illustrating some potentially generic effects of fire on aquatic ecosystems. 

PMID- 24278365
TI  - A Rad53 independent function of Rad9 becomes crucial for genome maintenance in
      the absence of the Recq helicase Sgs1.
AB  - The conserved family of RecQ DNA helicases consists of caretaker tumour
      suppressors, that defend genome integrity by acting on several pathways of DNA
      repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ
      helicase and it has been implicated in checkpoint responses, replisome stability
      and dissolution of double Holliday junctions during homologous recombination. In
      this study we investigate a possible genetic interaction between SGS1 and RAD9 in
      the cellular response to methyl methane sulphonate (MMS) induced damage and
      compare this with the genetic interaction between SGS1 and RAD24. The Rad9
      protein, an adaptor for effector kinase activation, plays well-characterized
      roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a
      sensor protein also in the DNA damage checkpoint response. Here we unveil novel
      insights into the cellular response to MMS-induced damage. Specifically, we show
      a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS
      induced damage and for suppression of gross chromosomal rearrangements, which is
      not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function
      of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1.
      Despite this, our dissection of the MMS checkpoint response reveals parallel, but
      unequal pathways for Rad53 activation and highlights significant differences
      between MMS- and hydroxyurea (HU)-induced checkpoint responses with relation to
      the requirement of the Sgs1 interacting partner Topoisomerase III (Top3). Thus,
      whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU
      induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3
      together define a minor but parallel pathway to that of Rad9. 

PMID- 24278368
TI  - Space-for-time substitution works in everglades ecological forecasting models.
AB  - Space-for-time substitution is often used in predictive models because long-term
      time-series data are not available. Critics of this method suggest factors other
      than the target driver may affect ecosystem response and could vary spatially,
      producing misleading results. Monitoring data from the Florida Everglades were
      used to test whether spatial data can be substituted for temporal data in
      forecasting models. Spatial models that predicted bluefin killifish (Lucania
      goodei) population response to a drying event performed comparably and sometimes
      better than temporal models. Models worked best when results were not
      extrapolated beyond the range of variation encompassed by the original dataset.
      These results were compared to other studies to determine whether ecosystem
      features influence whether space-for-time substitution is feasible. Taken in the
      context of other studies, these results suggest space-for-time substitution may
      work best in ecosystems with low beta-diversity, high connectivity between sites,
      and small lag in organismal response to the driver variable. 

PMID- 24278369
TI  - Stimulation of GABA-induced Ca2+ influx enhances maturation of human induced
      pluripotent stem cell-derived neurons.
AB  - Optimal use of patient-derived, induced pluripotent stem cells for modeling
      neuronal diseases is crucially dependent upon the proper physiological maturation
      of derived neurons. As a strategy to develop defined differentiation protocols
      that optimize electrophysiological function, we investigated the role of Ca(2+)
      channel regulation by astrocyte conditioned medium in neuronal maturation, using
      whole-cell patch clamp and Ca(2+) imaging. Standard control medium supported
      basic differentiation of induced pluripotent stem cell-derived neurons, as
      assayed by the ability to fire simple, single, induced action potentials. In
      contrast, treatment with astrocyte conditioned medium elicited complex and
      spontaneous neuronal activity, often with rhythmic and biphasic characteristics.
      Such augmented spontaneous activity correlated with astrocyte conditioned medium
      evoked hyperpolarization and was dependent upon regulated function of L-, N- and
      R-type Ca(2+) channels. The requirement for astrocyte conditioned medium could be
      substituted by simply supplementing control differentiation medium with high
      Ca(2+) or gamma-amino butyric acid (GABA). Importantly, even in the absence of
      GABA signalling, opening Ca(2+) channels directly using Bay K8644 was able to
      hyperpolarise neurons and enhance excitability, producing fully functional
      neurons. These data provide mechanistic insight into how secreted astrocyte
      factors control differentiation and, importantly, suggest that pharmacological
      modulation of Ca(2+) channel function leads to the development of a defined
      protocol for improved maturation of induced pluripotent stem cell-derived
      neurons. 

PMID- 24278370
TI  - Inferring the perturbed microRNA regulatory networks in cancer using hierarchical
      gene co-expression signatures.
AB  - MicroRNAs (miRNAs), a class of endogenous small regulatory RNAs, play important
      roles in many biological and physiological processes. The perturbations of some
      miRNAs, which are usually called as onco-microRNAs (onco-miRs), are significantly
      associated with multiple stages of cancer. Although hundreds of miRNAs have been
      discovered, the perturbed miRNA regulatory networks and their functions are still
      poorly understood in cancer. Analyzing the expression patterns of miRNA target
      genes is a very useful strategy to infer the perturbed miRNA networks. However,
      due to the complexity of cancer transcriptome, current methods often encounter
      low sensitivity and report few onco-miR candidates. Here, we developed a new
      method, named miRHiC (enrichment analysis of miRNA targets in Hierarchical gene
      Co-expression signatures), to infer the perturbed miRNA regulatory networks by
      using the hierarchical co-expression signatures in large-scale cancer gene
      expression datasets. The method can infer onco-miR candidates and their target
      networks which are only linked to sub-clusters of the differentially expressed
      genes at fine scales of the co-expression hierarchy. On two real datasets of lung
      cancer and hepatocellular cancer, miRHiC uncovered several known onco-miRs and
      their target genes (such as miR-26, miR-29, miR-124, miR-125 and miR-200) and
      also identified many new candidates (such as miR-149, which is inferred in both
      types of cancers). Using hierarchical gene co-expression signatures, miRHiC can
      greatly increase the sensitivity for inferring the perturbed miRNA regulatory
      networks in cancer. All Perl scripts of miRHiC and the detailed documents are
      freely available on the web at
      http://bioinfo.au.tsinghua.edu.cn/member/jgu/miRHiC/. 

PMID- 24278371
TI  - Integrating structure to protein-protein interaction networks that drive
      metastasis to brain and lung in breast cancer.
AB  - Blocking specific protein interactions can lead to human diseases. Accordingly,
      protein interactions and the structural knowledge on interacting surfaces of
      proteins (interfaces) have an important role in predicting the genotype-phenotype
      relationship. We have built the phenotype specific sub-networks of protein
      protein interactions (PPIs) involving the relevant genes responsible for lung and
      brain metastasis from primary tumor in breast cancer. First, we selected the PPIs
      most relevant to metastasis causing genes (seed genes), by using the "guilt-by
      association" principle. Then, we modeled structures of the interactions whose
      complex forms are not available in Protein Databank (PDB). Finally, we mapped
      mutations to interface structures (real and modeled), in order to spot the
      interactions that might be manipulated by these mutations. Functional analyses
      performed on these sub-networks revealed the potential relationship between
      immune system-infectious diseases and lung metastasis progression, but this
      connection was not observed significantly in the brain metastasis. Besides,
      structural analyses showed that some PPI interfaces in both metastasis sub
      networks are originating from microbial proteins, which in turn were mostly
      related with cell adhesion. Cell adhesion is a key mechanism in metastasis,
      therefore these PPIs may be involved in similar molecular pathways that are
      shared by infectious disease and metastasis. Finally, by mapping the mutations
      and amino acid variations on the interface regions of the proteins in the
      metastasis sub-networks we found evidence for some mutations to be involved in
      the mechanisms differentiating the type of the metastasis. 

PMID- 24278372
TI  - Characterization of persistent virus-like particles in two acetate-fed
      methanogenic reactors.
AB  - The objective of this study was to characterize the morphology, size
      distribution, concentration and genome size of virus-like particles (VLPs) in two
      acetate-fed Methanosaeta-dominated reactors to better understand the possible
      correlation between viruses and archaeal hosts. The study reactors were dominated
      by a single genus of acetoclastic methanogen, Methanosaeta, which was present at
      6 to 13 times higher than the combined bacterial populations consisting of
      Proteobacteria, Firmicutes, and Bacteroidetes. Epifluorescent microscopy showed
      VLPs concentration of 7.1 +/- 1.5 * 10(7) VLPs/ml and 8.4 +/- 4.3 * 10(7) VLPs/ml
      in the two laboratory reactors. Observations of no detectable import of VLPs with
      the reactor feed combined long operational time since the last inocula were
      introduced suggests that the VLP populations were actively propagating in the
      reactors. Transmission electron microscopy images showed VLPs with morphology
      consistent with Siphoviridae in both reactors, and VLPs with morphologies
      consistent with Myoviridae in one of the reactors. The morphology, size
      distribution and genome size of VLPs were distinct between reactors suggesting
      that unique viral populations inhabited each reactor, though the hosts of these
      VLPs remain unclear.

PMID- 24278373
TI  - Binding, transcytosis and biodistribution of anti-PECAM-1 iron oxide
      nanoparticles for brain-targeted delivery.
AB  - OBJECTIVE: Characterize the flux of platelet-endothelial cell adhesion molecule
      (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs)
      across the blood-brain barrier (BBB) and its biodistribution in vitro and in
      vivo. METHODS: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized
      in house. The binding affinity of these nanoparticles was investigated using
      human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were
      performed using a hCMEC/D3 BBB model. To test their immunospecificity index and
      biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid
      infusion. The capillary depletion method was used to elucidate their distribution
      between the BBB and brain parenchyma. RESULTS: Anti-PECAM-1 IONPs were ~130 nm.
      The extent of nanoparticle antibody surface coverage was 63.6 +/- 8.4%. Only 6.39
      +/- 1.22% of labeled antibody dissociated from IONPs in heparin-treated whole
      blood over 4 h. The binding affinity of PECAM-1 antibody (KD) was 32 nM with a
      maximal binding (Bmax) of 17 * 10(5) antibody molecules/cell. Anti-PECAM-1 IONP
      flux across a hCMEC/D3 monolayer was significantly higher than IgG IONP's with
      31% of anti-PECAM-1 IONPs in the receiving chamber after 6 h. Anti-PECAM-1 IONPs
      showed higher concentrations in lung and brain, but not liver or spleen, than IgG
      IONPs after infusion. The capillary depletion method showed that 17+/-12% of the
      anti-PECAM-1 IONPs crossed the BBB into the brain ten minutes after infusion.
      CONCLUSIONS: PECAM-1 antibody coating significantly increased IONP flux across
      the hCMEC/D3 monolayer. In vivo results showed that the PECAM-1 antibody enhanced
      BBB association and brain parenchymal accumulation of IONPs compared to IgG. This
      research demonstrates the benefit of anti-PECAM-1 IONPs for association and flux
      across the BBB into the brain in relation to its biodistribution in peripheral
      organs. The results provide insight into potential application and toxicity
      concerns of anti-PECAM-1 IONPs in the central nervous system.

PMID- 24278375
TI  - A nation-wide multicenter retrospective study of the epidemiological,
      pathological and clinical characteristics of breast cancer in situ in Chinese
      women in 1999 - 2008.
AB  - BACKGROUND: Compared with invasive breast cancer, breast cancer in situ (BCIS) is
      seldom life threatening. However, an increasing incidence has been observed in
      recent years over the world. The purpose of our study is to investigate the
      epidemiological, clinical and pathological profiles of BCIS in Chinese women from
      1999-2008. METHODS: Four thousand and two hundred-eleven female breast cancer
      (BC) patients were enrolled in this hospital-based nation-wide and multi-center
      retrospective study. Patients were randomly selected from seven hospitals in
      seven representative geographical regions of China between 1999 and 2008. The
      epidemiological, clinical and pathological data were collected based on the
      designed case report form (CRF). RESULTS: There were one hundred and forty-three
      BCIS cases in four thousand and two hundred-eleven BC patients (3.4%). The mean
      age at diagnosis was 48.3 years and BCIS peaked in age group 40-49 yrs (39.9%).
      The most common subtype was ductal carcinoma in situ (DCIS) (88.0%). 53.8% were
      positive for estrogen receptor (ER). Human epidermal growth factor receptor 2
      (HER2) positive status was observed in 23.8% of patients. All patients underwent
      surgeries and 14.7% of them had breast conservation therapies (BCT) (21/143), but
      41.9% accepted chemotherapy (64/143). Much less patients underwent radiotherapy
      (16.0%, 23/143) and among patients who had BCT, 67% accepted radiotherapy
      (14/21). Endocrine therapy was taken in 44.1% patients (63/143). CONCLUSIONS: The
      younger age of BCIS among Chinese women than Western countries and increasing
      number of cases pose a great challenge. BCT and endocrine therapy are under great
      needs.

PMID- 24278374
TI  - Timing of muscle response to a sudden leg perturbation: comparison between
      adolescents and adults with Down syndrome.
AB  - Movement disturbances associated with Down syndrome reduce mechanical stability,
      worsening the execution of important tasks such as walking and upright standing.
      To compensate these deficits, persons with Down syndrome increase joint stability
      modulating the level of activation of single muscles or producing an agonist
      antagonist co-activation. Such activations are also observed when a relaxed,
      extended leg is suddenly released and left to oscillate passively under the
      influence of gravity (Wartenberg test). In this case, the Rectus femoris of
      adults with Down syndrome displayed peaks of activation after the onset of the
      first leg flexion. With the aim to verify if these muscular reactions were
      acquired during the development time and to find evidences useful to give them a
      functional explanation, we used the Wartenberg test to compare the knee joint
      kinematics and the surface electromyography of the Rectus femoris and Biceps
      femoris caput longus between adolescents and adults with Down syndrome. During
      the first leg flexion, adolescents and adults showed single Rectus femoris
      activations while, a restricted number of participants exhibited agonist
      antagonist co-activations. However, regardless the pattern of activation, adults
      initiated the muscle activity significantly later than adolescents. Although most
      of the mechanical parameters and the total movement variability were similar in
      the two groups, the onset of the Rectus femoris activation was well correlated
      with the time of the minimum acceleration variability. Thus, in adolescents the
      maximum mechanical stability occurred short after the onset of the leg fall,
      while adults reached their best joint stability late during the first flexion.
      These results suggest that between the adolescence and adulthood, persons with
      Down syndrome explore a temporal window to select an appropriate timing of muscle
      activation to overcome their inherent mechanical instability. 

PMID- 24278376
TI  - Lack of plasma kallikrein-kinin system cascade in teleosts.
AB  - The kallikrein-kinin system (KKS) consists of two major cascades in mammals:
      "plasma KKS" consisting of high molecular-weight (HMW) kininogen (KNG), plasma
      kallikrein (KLKB1), and bradykinin (BK); and "tissue KKS" consisting of low
      molecular-weight (LMW) KNG, tissue kallikreins (KLKs), and [Lys(0)]-BK. Some
      components of the KKS have been identified in the fishes, but systematic analyses
      have not been performed, thus this study aims to define the KKS components in
      teleosts and pave a way for future physiological and evolutionary studies.
      Through a combination of genomics, molecular, and biochemical methods, we showed
      that the entire plasma KKS cascade is absent in teleosts. Instead of two KNGs as
      found in mammals, a single molecular weight KNG was found in various teleosts,
      which is homologous to the mammalian LMW KNG. Results of molecular phylogenetic
      and synteny analyses indicated that the all current teleost genomes lack KLKB1,
      and its unique protein structure, four apple domains and one trypsin domain,
      could not be identified in any genome or nucleotide databases. We identified some
      KLK-like proteins in teleost genomes by synteny and conserved domain analyses,
      which could be the orthologs of tetrapod KLKs. A radioimmunoassay system was
      established to measure the teleost BK and we found that [Arg(0)]-BK is the major
      circulating form instead of BK, which supports that the teleost KKS is similar to
      the mammalian tissue KKS. Coincidently, coelacanths are the earliest vertebrate
      that possess both HMW KNG and KLKB1, which implies that the plasma KKS could have
      evolved in the early lobe-finned fish and descended to the tetrapod lineage. The
      co-evolution of HMW KNG and KLKB1 in lobe-finned fish and early tetrapods may
      mark the emergence of the plasma KKS and a contact activation system in blood
      coagulation, while teleosts may have retained a single KKS cascade. 

PMID- 24278377
TI  - Risk factors for fatality among confirmed adult dengue inpatients in Singapore: a
      matched case-control study.
AB  - OBJECTIVES: To identify demographic, clinical and laboratory risk factors for
      death due to dengue fever in adult patients in Singapore. METHODS: Multi-center
      retrospective study of hospitalized adult patients with confirmed dengue fever in
      Singapore between 1 January 2004 and 31 December 2008. Non-fatal controls were
      selected by matching age and year of infection with fatal cases. World Health
      Organization 1997, 2009 criteria were applied to define dengue hemorrhagic fever
      (DHF), warning signs and severe dengue. Statistical significance was assessed by
      conditional logistic regression modeling. RESULTS: Significantly more fatal cases
      than matched controls had pre-existing co-morbid conditions, and presented with
      abdominal pain/tenderness. Median pulse rates were significantly higher while
      myalgia was significantly less frequent in cases. . Fatal cases also had higher
      leucocyte counts, platelet counts, serum sodium, potassium, urea, creatine and
      bilirubin levels on admission compared to controls. There was no statistical
      significant difference between the prevalence of DHF and hematocrit level among
      cases and controls. Multivariate analysis showed myalgia and leucocyte count at
      presentation were independent predictors of fatality (adjusted odds ratios 0.09
      and 2.94 respectively). None of the controls was admitted to intensive care unit
      (ICU) or given blood transfusion, while 71.4% and 28.6% of fatal cases received
      ICU admission and blood transfusion. CONCLUSIONS: Absence of myalgia and
      leucocytosis on admission were independently associated with fatality in our
      matched case-control study. Fatalities were also commonly associated with co
      morbidities and clinicians should be alarmed if dengue patients fulfilled severe
      dengue case definition on admission.

PMID- 24278378
TI  - A novel in vitro model for microvasculature reveals regulation of circumferential
      ECM organization by curvature.
AB  - In microvascular vessels, endothelial cells are aligned longitudinally whereas
      several components of the extracellular matrix (ECM) are organized
      circumferentially. While current three-dimensional (3D) in vitro models for
      microvasculature have allowed the study of ECM-regulated tubulogenesis, they have
      limited control over topographical cues presented by the ECM and impart a barrier
      for the high-resolution and dynamic study of multicellular and extracellular
      organization. Here we exploit a 3D fibrin microfiber scaffold to develop a novel
      in vitro model of the microvasculature that recapitulates endothelial alignment
      and ECM deposition in a setting that also allows the sequential co-culture of
      mural cells. We show that the microfibers' nanotopography induces longitudinal
      adhesion and alignment of endothelial colony-forming cells (ECFCs), and that
      these deposit circumferentially organized ECM. We found that ECM wrapping on the
      microfibers is independent of ECFCs' actin and microtubule organization, but it
      is dependent on the curvature of the microfiber. Microfibers with smaller
      diameters (100-400 um) guided circumferential ECM deposition, whereas microfibers
      with larger diameters (450 um) failed to support wrapping ECM. Finally, we
      demonstrate that vascular smooth muscle cells attached on ECFC-seeded
      microfibers, depositing collagen I and elastin. Collectively, we establish a
      novel in vitro model for the sequential control and study of microvasculature
      development and reveal the unprecedented role of the endothelium in organized ECM
      deposition regulated by the microfiber curvature. 

PMID- 24278379
TI  - Saccades improve postural control: a developmental study in normal children.
AB  - INTRODUCTION: Dual-task performance is known to affect postural stability in
      children. This study focused on the effect of oculomotor tasks like saccadic eye
      movements on postural stability, studied in a large population of children by
      recording simultaneously their eye movements and posture. MATERIALS AND METHODS:
      Ninety-five healthy children from 5.8 to 17.6 years old were examined. All
      children were free of any vestibular, neurological, ophtalmologic and orthoptic
      abnormalities. Postural control was measured with a force platform
      TechnoConcept(r), and eye movements with video oculography (MobilEBT(r)).
      Children performed two oculomotor tasks: fixation of a stable central target and
      horizontal saccades. We measured the saccade latency and the number of saccades
      during fixation as well as the surface, length and mean velocity of the center of
      pressure. RESULTS: During postural measurement, we observed a correlation between
      the age on the one hand and a decrease in saccade latency as well as an
      improvement in the quality of fixation on the other. Postural sway decreases with
      age and is reduced in the dual task (saccades) in comparison with a simple task
      of fixation. DISCUSSION - CONCLUSION: These results suggest a maturation of
      neural circuits controlling posture and eye movements during childhood. This
      study also shows the presence of an interaction between the oculomotor system and
      the postural system. Engaging in oculomotor tasks results in a reduction of
      postural sway.

PMID- 24278380
TI  - Inhibition of nutlin-resistant HDM2 mutants by stapled peptides.
AB  - Pharmacological modulation of p53 activity is an attractive therapeutic strategy
      in cancers with wild-type p53. Presently in clinical trials, the small molecule
      Nutlin-3A competitively binds to HDM2, a key negative regulator of p53 and blocks
      its activity. We have described resistance mutations in HDM2 that selectively
      reduce affinity for Nutlin but not p53. In the present communication, we show
      that stapled peptides targeting the same region of HDM2 as Nutlin are refractory
      to these mutations, and display reduced discrimination between the wild-type and
      mutant HDM2s with regards to functional abrogation of interaction with p53. The
      larger interaction footprint afforded by stapled peptides suggests that this
      class of ligands may prove comparatively more resilient to acquired resistance in
      a clinical setting. 

PMID- 24278381
TI  - Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9
      polyomaviruses found on the skin.
AB  - The polyomavirus family is rapidly expanding with twelve new human viruses
      identified since 2007. A significant number of the new human polyomaviruses
      (HPyV) has been found on the skin. Whether these viruses share biological
      properties and should be grouped together is unknown. Here we investigated the
      serological behavior of cutaneous HPyVs in a general population. 799 sera from
      immunocompetent Australian individuals aged between 0-87 were analyzed with a
      Luminex xMAP technology-based immunoassay for the presence of VP1-directed IgG
      antibodies against MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and BKPyV as a control.
      Except for HPyV9, overall seropositivity was high for the cutanous polyomaviruses
      (66-81% in adults), and gradually increased with age. Children below 6 months
      displayed seropositivity rates comparable to the adults, indicative of maternal
      antibodies. TSPyV seroreactivity levels strongly increased after age 2 and waned
      later in life comparable to BKPyV, whereas MCPyV, HPyV6 and HPyV7 seroreactivity
      remained rather stable throughout. Based on the identified serologic profiles,
      MCPyV seems to cluster with HPyV6 and HPyV7, and TSPyV and HPyV9 by themselves.
      These profiles indicate heterogeneity among cutaneous polyomaviruses and probably
      reflect differences in exposure and pathogenic behavior of these viruses. 

PMID- 24278382
TI  - In vivo quantitative susceptibility mapping (QSM) in Alzheimer's disease.
AB  - BACKGROUND: This study explores the magnetostatic properties of the Alzheimer's
      disease brain using a recently proposed, magnetic resonance imaging,
      postprocessed contrast mechanism. Quantitative susceptibility mapping (QSM) has
      the potential to monitor in vivo iron levels by reconstructing magnetic
      susceptibility sources from field perturbations. However, with phase data
      acquired at a single head orientation, the technique relies on several
      theoretical approximations and requires fast-evolving regularisation strategies.
      METHODS: In this context, the present study describes a complete methodological
      framework for magnetic susceptibility measurements with a review of its
      theoretical foundations. FINDINGS AND SIGNIFICANCE: The regional and whole-brain
      cross-sectional comparisons between Alzheimer's disease subjects and matched
      controls indicate that there may be significant magnetic susceptibility
      differences for deep brain nuclei--particularly the putamen--as well as for
      posterior grey and white matter regions. The methodology and findings described
      suggest that the QSM method is ready for larger-scale clinical studies.

PMID- 24278383
TI  - De novo assembly and characterization of the global transcriptome for Rhyacionia
      leptotubula using Illumina paired-end sequencing.
AB  - BACKGROUND: The pine tip moth, Rhyacionia leptotubula (Lepidoptera: Tortricidae)
      is one of the most destructive forestry pests in Yunnan Province, China. Despite
      its importance, less is known regarding all aspects of this pest. Understanding
      the genetic information of it is essential for exploring the specific traits at
      the molecular level. Thus, we here sequenced the transcriptome of R. leptotubula
      with high-throughput Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: In a
      single run, more than 60 million sequencing reads were generated. De novo
      assembling was performed to generate a collection of 46,910 unigenes with mean
      length of 642 bp. Based on Blastx search with an E-value cut-off of 10(-5),
      22,581 unigenes showed significant similarities to known proteins from National
      Center for Biotechnology Information (NCBI) non-redundant (Nr) protein database.
      Of these annotated unigenes, 10,360, 6,937 and 13,894 were assigned to Gene
      Ontology (GO), Clusters of Orthologous Group (COG), and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) databases, respectively. A total of 5,926 unigenes were
      annotated with domain similarity derived functional information, of which 55 and
      39 unigenes respectively encoding the insecticide resistance related enzymes,
      cytochrome P450 and carboxylesterase. Using the transcriptome data, 47 unigenes
      belonging to the typical "stress" genes of heat shock protein (Hsp) family were
      retrieved. Furthermore, 1,450 simple sequence repeats (SSRs) were detected; 3.09%
      of the unigenes contained SSRs. Large numbers of SSR primer pairs were designed
      and out of randomly verified primer pairs 80% were successfully yielded
      amplicons. CONCLUSIONS/SIGNIFICANCE: A large of putative R. leptotubula
      transcript sequences has been obtained from the deep sequencing, which
      extensively increases the comprehensive and integrated genomic resources of this
      pest. This large-scale transcriptome dataset will be an important information
      platform for promoting our investigation of the molecular mechanisms from various
      aspects in this species.

PMID- 24278384
TI  - The olfactory bulb in newborn piglet is a reservoir of neural stem and progenitor
      cells.
AB  - The olfactory bulb (OB) periventricular zone is an extension of the forebrain
      subventricular zone (SVZ) and thus is a source of neuroprogenitor cells and
      neural stem cells. While considerable information is available on the SVZ-OB
      neural stem cell (NSC)/neuroprogenitor cell (NPC) niche in rodents, less work has
      been done on this system in large animals. The newborn piglet is used as a
      preclinical translational model of neonatal hypoxic-ischemic brain damage, but
      information about the endogenous sources of NSCs/NPCs in piglet is needed to
      implement endogenous or autologous cell-based therapies in this model. We
      characterized NSC/NPC niches in piglet forebrain and OB-SVZ using western
      blotting, histological, and cell culture methods. Immunoblotting revealed nestin,
      a NSC/NPC marker, in forebrain-SVZ and OB-SVZ in newborn piglet. Several
      progenitor or newborn neuron markers, including Dlx2, musashi, doublecortin, and
      polysialated neural cell adhesion molecule were also detected in OB-SVZ by
      immunoblotting. Immunohistochemistry confirmed the presence of nestin, musashi,
      and doublecortin in forebrain-SVZ and OB-SVZ. Bromodeoxyuridine (BrdU) labeling
      showed that the forebrain-SVZ and OB-SVZ accumulate newly replicated cells. BrdU
      positive cells were immunolabeled for astroglial, oligodendroglial, and neuronal
      markers. A lateral migratory pathway for newly born neuron migration to primary
      olfactory cortex was revealed by BrdU labeling and co-labeling for doublecortin
      and class III beta tubulin. Isolated and cultured forebrain-SVZ and OB-SVZ cells
      from newborn piglet had the capacity to generate numerous neurospheres. Single
      cell clonal analysis of neurospheres revealed the capacity for self-renewal and
      multipotency. Neurosphere-derived cells differentiated into neurons, astrocytes,
      and oligodendrocytes and were amenable to permanent genetic tagging with
      lentivirus encoding green fluorescent protein. We conclude that the piglet OB-SVZ
      is a reservoir of NSCs and NPCs suitable to use in autologous cell therapy in
      preclinical models of neonatal/pediatric brain injury. 

PMID- 24278385
TI  - Evidence for an association between post-fledging dispersal and microsatellite
      multilocus heterozygosity in a large population of greater flamingos.
AB  - Dispersal can be divided into three stages: departure, transience and settlement.
      Despite the fact that theoretical studies have emphasized the importance of
      heterozygosity on dispersal strategies, empirical evidence of its effect on
      different stages of dispersal is lacking. Here, using multi-event capture-mark
      recapture models, we show a negative association between microsatellite
      multilocus heterozygosity (MLH; 10 loci; n = 1023) and post-fledging dispersal
      propensity for greater flamingos, Phoenicopterus roseus, born in southern France.
      We propose that the negative effects of inbreeding depression affects competitive
      ability and therefore more homozygous individuals are more likely to disperse
      because they are less able to compete within the highly saturated natal site.
      Finally, a model with the effect of MLH on propensity of post-fledgling
      dispersers to disperse to the long-distance sites of Africa was equivalent to the
      null model, suggesting that MLH had low to no effect on dispersal distance.
      Variations in individual genetic quality thus result in context-dependent
      heterogeneity in dispersal strategies at each stage of dispersal. Our results
      have important implications on fitness since sites visited early in life are
      known to influence site selection later on in life and future survival.

PMID- 24278386
TI  - Effectiveness of bisphosphonate analogues and functional electrical stimulation
      on attenuating post-injury osteoporosis in spinal cord injury patients- a
      systematic review and meta-analysis.
AB  - BACKGROUND: Various pharmacologic and non-pharmacologic approaches have been
      applied to reduce sublesional bone loss after spinal cord injury (SCI), and the
      results are inconsistent across the studies. The objective of this meta-analysis
      was to investigate whether the two most-studied interventions, bisphosphonate
      analogues and functional electrical stimulation (FES), could effectively decrease
      bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI
      population. METHODS: Randomized controlled trials, quasi-experimental studies,
      and prospective follow-up studies employing bisphosphonates or FES to treat post
      SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was
      the percentage of BMD change from baseline measured by dual-energy X-ray
      absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four
      points: the 3rd, 6th, 12th, and 18th month after intervention. RESULTS: A total
      of 19 studies were included in the analysis and involved 364 patients and 14
      healthy individuals. Acute SCI participants treated with bisphosphonate therapy
      demonstrated a trend toward less bone loss than participants who received
      placebos or usual care. A significant difference in BMD decline was noted between
      both groups at the 3rd and 12th month post-medication. The subgroup analysis
      failed to show the superiority of intravenous bisphosphonate over oral
      administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI,
      2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to
      16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment,
      respectively. The studies employing FES >= 5 days per week were likely to have
      better effectiveness than studies using FES <= 3 days per week. CONCLUSIONS: Our
      meta-analysis indicated bisphosphonate administration early following SCI
      effectively attenuated sublesional bone loss. FES intervention for chronic SCI
      patients could significantly increase sublesional BMD near the site of maximal
      mechanical loading.

PMID- 24278387
TI  - Targeted selected reaction monitoring mass spectrometric immunoassay for insulin
      like growth factor 1.
AB  - Insulin-like growth factor 1 (IGF1) is an important biomarker of human growth
      disorders that is routinely analyzed in clinical laboratories. Mass spectrometry
      based workflows offer a viable alternative to standard IGF1 immunoassays, which
      utilize various pre-analytical preparation strategies. In this work we developed
      an assay that incorporates a novel sample preparation method for dissociating
      IGF1 from its binding proteins. The workflow also includes an immunoaffinity step
      using antibody-derivatized pipette tips, followed by elution, trypsin digestion,
      and LC-MS/MS separation and detection of the signature peptides in a selected
      reaction monitoring (SRM) mode. The resulting quantitative mass spectrometric
      immunoassay (MSIA) exhibited good linearity in the range of 1 to 1,500 ng/mL
      IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest
      limits of detection of 1 ng/mL. The linearity and recovery characteristics of the
      assay were also established, and the new method compared to a commercially
      available immunoassay using a large cohort of human serum samples. The IGF1 SRM
      MSIA is well suited for use in clinical laboratories. 

PMID- 24278388
TI  - One-carbon metabolism pathway gene variants and risk of clear cell renal cell
      carcinoma in a Chinese population.
AB  - BACKGROUND: One-carbon metabolism is the basement of nucleotide synthesis and the
      methylation of DNA linked to cancer risk. Variations in one-carbon metabolism
      genes are reported to affect the risk of many cancers, including renal cancer,
      but little knowledge about this mechanism is known in Chinese population.
      METHODS: Each subject donated 5 mL venous blood after signing the agreement. The
      study was approved by the Institutional Review Board of the Nanjing Medical
      University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes
      (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal
      cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot.
      RESULTS: Strong associations with ccRCC risk were observed for rs706209 (P =
      0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none
      variant allele, individuals carrying one or more variant alleles in these two
      genes had a statistically significantly decreased risk of ccRCC [P = 0.001,
      adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06-0.90]. In
      addition, patients carrying one or more variant alleles were more likely to
      develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95%CI = 1.11
      1.69) and well-differentiated ccRCC (P<0.001, adjusted OR = 1.42, 95%CI = 0.87
      1.68). In the subgroup analysis, individuals carrying none variant allele in
      older group (P = 0.007, adjusted OR = 0.67, 95%CI = 0.49-0.91), male group (P =
      0.007, adjusted OR = 0.71, 95%CI = 0.55-0.92), never smoking group (P = 0.002,
      adjusted OR = 0.68, 95%CI = 0.53-0.88) and never drinking group (P<0.001,
      adjusted OR = 0.68, 95%CI = 0.53-0.88) had an increased ccRCC risk. CONCLUSIONS:
      Our results suggest that the polymorphisms of the one-carbon metabolism-related
      genes are associated with ccRCC risk in Chinese population. Future population
      based prospective studies are required to confirm the results.

PMID- 24278389
TI  - The effect of adding CO2 to hypoxic inspired gas on cerebral blood flow velocity
      and breathing during incremental exercise.
AB  - Hypoxia increases the ventilatory response to exercise, which leads to
      hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood
      flow (CBF). We studied the effects of adding CO2 to a hypoxic inspired gas on CBF
      during heavy exercise in an altitude naive population. We hypothesized that
      augmented inspired CO2 and hypoxia would exert synergistic effects on increasing
      CBF during exercise, which would improve exercise capacity compared to hypocapnic
      hypoxia. We also examined the responsiveness of CO2 and O2 chemoreception on the
      regulation ventilation ([Formula: see text]E) during incremental exercise. We
      measured middle cerebral artery velocity (MCAv; index of CBF), [Formula: see
      text]E, end-tidal PCO2, respiratory compensation threshold (RC) and ventilatory
      response to exercise ([Formula: see text]E slope) in ten healthy men during
      incremental cycling to exhaustion in normoxia and hypoxia (FIO2 = 0.10) with and
      without augmenting the fraction of inspired CO2 (FICO2). During exercise in
      normoxia, augmenting FICO2 elevated MCAv throughout exercise and lowered both RC
      onset and[Formula: see text]E slope below RC (P<0.05). In hypoxia, MCAv and
      [Formula: see text]E slope below RC during exercise were elevated, while the
      onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO2 in
      hypoxia increased [Formula: see text]E at RC (P<0.05) but no difference was
      observed in RC onset, MCAv, or [Formula: see text]E slope below RC (P>0.05). The
      [Formula: see text]E slope above RC was unchanged with either hypoxia or
      augmented FICO2 (P>0.05). We found augmenting FICO2 increased CBF during sub
      maximal exercise in normoxia, but not in hypoxia, indicating that the 'normal'
      cerebrovascular response to hypercapnia is blunted during exercise in hypoxia,
      possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may
      explain the lack of improvement of exercise capacity in hypoxia with augmented
      CO2. Our data further indicate that, during exercise below RC, chemoreception is
      responsive, while above RC the ventilatory response to CO2 is blunted.

PMID- 24278390
TI  - Involvement of TGFbeta-induced phosphorylation of the PTEN C-terminus on TGFbeta
      induced acquisition of malignant phenotypes in lung cancer cells.
AB  - Transforming growth factor beta (TGFbeta) derived from the tumor microenvironment
      induces malignant phenotypes such as epithelial-mesenchymal transition (EMT) and
      aberrant cell motility in lung cancers. TGFbeta-induced translocation of beta
      catenin from E-cadherin complexes into the cytoplasm is involved in the
      transcription of EMT target genes. PTEN (phosphatase and tensin homologue deleted
      from chromosome 10) is known to exert phosphatase activity by binding to E
      cadherin complexes via beta-catenin, and recent studies suggest that
      phosphorylation of the PTEN C-terminus tail might cause loss of this PTEN
      phosphatase activity. However, whether TGFbeta can modulate both beta-catenin
      translocation and PTEN phosphatase activity via phosphorylation of the PTEN C
      terminus remains elusive. Furthermore, the role of phosphorylation of the PTEN C
      terminus in TGFbeta-induced malignant phenotypes has not been evaluated. To
      investigate whether modulation of phosphorylation of the PTEN C-terminus can
      regulate malignant phenotypes, here we established lung cancer cells expressing
      PTEN protein with mutation of phosphorylation sites in the PTEN C-terminus
      (PTEN4A). We found that TGFbeta stimulation yielded a two-fold increase in the
      phosphorylated -PTEN/PTEN ratio. Expression of PTEN4A repressed TGFbeta-induced
      EMT and cell motility even after snail expression. Our data showed that PTEN4A
      might repress EMT through complete blockade of beta-catenin translocation into
      the cytoplasm, besides the inhibitory effect of PTEN4A on TGFbeta-induced
      activation of smad-independent signaling pathways. In a xenograft model, the
      tumor growth ratio was repressed in cells expressing PTEN4A. Taken together,
      these data suggest that phosphorylation sites in the PTEN C-terminus might be a
      therapeutic target for TGFbeta-induced malignant phenotypes in lung cancer cells.

PMID- 24278391
TI  - Origin and characteristics of internal genes affect infectivity of the novel
      avian-origin influenza A (H7N9) virus.
AB  - BACKGROUND: Human infection with a novel avian-origin influenza A (H7N9) virus
      occurred continuously in China during the first half of 2013, with high
      infectivity and pathogenicity to humans. In this study, we investigated the
      origin of internal genes of the novel H7N9 virus and analyzed the relationship
      between internal genes and infectivity of the virus. METHODOLOGY AND PRINCIPAL
      FINDINGS: We tested the environmental specimens using real-time RT-PCR assays and
      isolated five H9N2 viruses from specimens that were positive for both H7 and H9.
      Results of recombination and phylogeny analysis, performed based on the entire
      sequences of 221 influenza viruses, showed that one of the Zhejiang avian H9N2
      isolates, A/environment/Zhejiang/16/2013, shared the highest identities on the
      internal genes with the novel H7N9 virus A/Anhui/1/2013, ranging from 98.98% to
      100%. Zhejiang avian H9N2 isolates were all reassortant viruses, by acquiring NS
      gene from A/chicken/Dawang/1/2011-like viruses and other five internal genes from
      A/brambling/Beijing/16/2012-like viruses. Compared to A/Anhui/1/2013 (H7N9), the
      homology on the NS gene was 99.16% with A/chicken/Dawang/1/2011, whereas only
      94.27-97.61% with A/bramnling/Beijing/16/2012-like viruses. Analysis on the
      relationship between internal genes and the infectivity of novel H7N9 viruses
      were performed by comparing amino acid sequences with the HPAI H5N1 viruses, the
      H9N2 and the earlier H7N9 avian influenza viruses. There were nine amino acids on
      the internal genes found to be possibly associated with the infectivity of the
      novel H7N9 viruses. CONCLUSIONS: These findings indicate that the internal genes,
      sharing the highest similarities with A/environment/Zhejiang/16/2013-like (H9N2)
      viruses, may affect the infectivity of the novel H7N9 viruses.

PMID- 24278392
TI  - Heterotrophic compensation: a possible mechanism for resilience of coral reefs to
      global warming or a sign of prolonged stress?
AB  - Thermally induced bleaching has caused a global decline in corals and the
      frequency of such bleaching events will increase. Thermal bleaching severely
      disrupts the trophic behaviour of the coral holobiont, reducing the
      photosynthetically derived energy available to the coral host. In the short term
      this reduction in energy transfer from endosymbiotic algae results in an energy
      deficit for the coral host. If the bleaching event is short-lived then the coral
      may survive this energy deficit by depleting its lipid reserves, or by increasing
      heterotrophic energy acquisition. We show for the first time that the coral
      animal is capable of increasing the amount of heterotrophic carbon incorporated
      into its tissues for almost a year following bleaching. This prolonged
      heterotrophic compensation could be a sign of resilience or prolonged stress. If
      the heterotrophic compensation is in fact an acclimatization response, then this
      physiological response could act as a buffer from future bleaching by providing
      sufficient heterotrophic energy to compensate for photoautotrophic energy losses
      during bleaching, and potentially minimizing the effect of subsequent elevated
      temperature stresses. However, if the elevated incorporation of zooplankton is a
      sign that the effects of bleaching continue to be stressful on the holobiont,
      even after 11 months of recovery, then this physiological response would indicate
      that complete coral recovery requires more than 11 months to achieve. If coral
      bleaching becomes an annual global phenomenon by mid-century, then present
      temporal refugia will not be sufficient to allow coral colonies to recover
      between bleaching events and coral reefs will become increasingly less resilient
      to future climate change. If, however, increasing their sequestration of
      zooplankton-derived nutrition into their tissues over prolonged periods of time
      is a compensating mechanism, the impacts of annual bleaching may be reduced.
      Thus, some coral species may be better equipped to face repeated bleaching stress
      than previously thought. 

PMID- 24278393
TI  - Associations between acute and chronic effects of exercise on indicators of
      metabolic health: a pilot training trial.
AB  - BACKGROUND: The interindividual variability in the health-related efficacy of
      regular endurance training is high. This impedes on the individual optimization
      of preventive training prescriptions when optimal efficacy is intended. As a
      consequence, health-gains remain below what could be achieved. Practicable
      predictors of an individual's responsiveness to physical exercise would offer a
      solution to this problem. Therefore, the present study aims to test the
      association of acute changes in indicators of metabolic health after an
      exhaustive exercise test and the respective chronic changes in response to an
      endurance training program. METHODS: Fasting blood samples of healthy, untrained,
      non-smoking subjects (n=12, age 49 +/- 7 years; body mass index 29 +/- 4; maximum
      oxygen uptake 34 +/- 7 ml . min(-1) . kg(-1)) were collected before and 1 hour
      after an exhaustive exercise test as well as after a 4 week supervised training
      period (walking / running 4 times per week at 60 % heart rate reserve). RESULTS:
      A close linear relationship between acute and chronic changes could be
      demonstrated for insulin concentration (p=0.001; r=0.83), the fasting indicator
      of insulin sensitivity HOMA-IR (p<0.001; r=0.78) and non-esterified fatty acid
      concentration (p=0.001; r=0.88). No association became apparent for standard
      blood lipid parameters. CONCLUSION: It is concluded that the magnitude of acute
      exercise-induced changes in indicators of insulin sensitivity and non-esterified
      fatty acid concentration is a promising candidate for the prediction of chronic
      training induced changes in the respective parameter. However, further studies
      are needed to assess predictive accuracy. TRIAL REGISTRATION:
      www.clinicaltrials.gov NCT00934206
      http://www.clinicaltrials.gov/ct2/show/NCT00934206.

PMID- 24278394
TI  - Integrative analysis of hereditary nonpolyposis colorectal cancer: the
      contribution of allele-specific expression and other assays to diagnostic
      algorithms.
AB  - The identification of germline variants predisposing to hereditary nonpolyposis
      colorectal cancer (HNPCC) is crucial for clinical management of carriers, but
      several probands remain negative for such variants or bear variants of uncertain
      significance (VUS). Here we describe the results of integrative molecular
      analyses in 132 HNPCC patients providing evidences for improved genetic testing
      of HNPCC with traditional or next generation methods. Patients were screened for:
      germline allele-specific expression (ASE), nucleotide variants, rearrangements
      and promoter methylation of mismatch repair (MMR) genes; germline EPCAM
      rearrangements; tumor microsatellite instability (MSI) and immunohistochemical
      (IHC) MMR protein expression. Probands negative for pathogenic variants of MMR
      genes were screened for germline APC and MUTYH sequence variants. Most germline
      defects identified were sequence variants and rearrangements of MMR genes.
      Remarkably, altered germline ASE of MMR genes was detected in 8/22 (36.5%)
      probands analyzed, including 3 cases negative at other screenings. Moreover, ASE
      provided evidence for the pathogenic role and guided the characterization of a
      VUS shared by 2 additional probands. No germline MMR gene promoter methylation
      was observed and only one EPCAM rearrangement was detected. In several cases,
      tumor IHC and MSI diverged from germline screening results. Notably, APC or
      biallelic MUTYH germline defects were identified in 2/19 probands negative for
      pathogenic variants of MMR genes. Our results show that ASE complements gDNA
      based analyses in the identification of MMR defects and in the characterization
      of VUS affecting gene expression, increasing the number of germline alterations
      detected. An appreciable fraction of probands negative for MMR gene variants
      harbors APC or MUTYH variants. These results indicate that germline ASE analysis
      and screening for APC and MUTYH defects should be included in HNPCC diagnostic
      algorithms. 

PMID- 24278395
TI  - Concatenation of observed grasp phases with observer's distal movements: a
      behavioural and TMS study.
AB  - The present study aimed at determining how actions executed by two conspecifics
      can be coordinated with each other, or more specifically, how the observation of
      different phases of a reaching-grasping action is temporary related to the
      execution of a movement of the observer. Participants observed postures of
      initial finger opening, maximal finger aperture, and final finger closing of
      grasp after observation of an initial hand posture. Then, they opened or closed
      their right thumb and index finger (experiments 1, 2 and 3). Response times
      decreased, whereas acceleration and velocity of actual finger movements increased
      when observing the two late phases of grasp. In addition, the results ruled out
      the possibility that this effect was due to salience of the visual stimulus when
      the hand was close to the target and confirmed an effect of even hand postures in
      addition to hand apparent motion due to the succession of initial hand posture
      and grasp phase. In experiments 4 and 5, the observation of grasp phases
      modulated even foot movements and pronunciation of syllables. Finally, in
      experiment 6, transcranial magnetic stimulation applied to primary motor cortex
      300 ms post-stimulus induced an increase in hand motor evoked potentials of
      opponens pollicis muscle when observing the two late phases of grasp. These data
      suggest that the observation of grasp phases induced simulation which was
      stronger during observation of finger closing. This produced shorter response
      times, greater acceleration and velocity of the successive movement. In general,
      our data suggest best concatenation between two movements (one observed and the
      other executed) when the observed (and simulated) movement was to be
      accomplished. The mechanism joining the observation of a conspecific's action
      with our own movement may be precursor of social functions. It may be at the
      basis for interactions between conspecifics, and related to communication between
      individuals. 

PMID- 24278396
TI  - Torsadogenic risk of antipsychotics: combining adverse event reports with drug
      utilization data across Europe.
AB  - BACKGROUND: Antipsychotics (APs) have been associated with risk of torsade de
      Pointes (TdP). This has important public health implications. Therefore, (a) we
      exploited the public FDA Adverse Event Reporting System (FAERS) to characterize
      their torsadogenic profile; (b) we collected drug utilization data from 12
      European Countries to assess the population exposure over the 2005-2010 period.
      METHODS: FAERS data (2004-2010) were analyzed based on the following criteria:
      (1) >= 4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR
      [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities,
      adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) >= 4 cases
      of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for
      VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA
      and SCD. Torsadogenic signals were characterized in terms of signal strength:
      from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E
      (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved
      from 12 European Countries and expressed as defined daily doses per 1,000
      inhabitants per day (DID). RESULTS: Thirty-five antipsychotics met at least one
      criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine,
      clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone,
      ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94
      DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents
      was found in several Countries (+3.47 in France): the exposure to olanzapine
      increased across all Countries (+1.84 in France) and peaked 2.96 in Norway;
      cyamemazine was typically used only in France (2.81 in 2009). Among Group B
      drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia).
      CONCLUSIONS: This parallel approach through spontaneous reporting and drug
      utilization analyses highlighted drug- and Country-specific scenarios requiring
      potential regulatory consideration: levomepromazine (Serbia), fluphenazine
      (Slovenia), olanzapine (across Europe), cyamemazine (France). This synergy should
      be encouraged to support future pharmacovigilance activities.

PMID- 24278397
TI  - Neuronal synapse formation induced by microglia and interleukin 10.
AB  - Recently, it was found that microglia regulated synaptic remodeling of the
      developing brain, but their mechanisms have not been well understood. In this
      study, the action of microglia on neuronal synapse formation was investigated,
      and the primary target of microglial processes was discovered. When the
      developing microglia were applied to cultured hippocampal neurons without direct
      contact, the numbers of dendritic spines and excitatory and inhibitory synapses
      significantly increased. In order to find out the main factor for synaptic
      formation, the effects of cytokines released from microglia were examined. When
      recombinant proteins of cytokines were applied to neuronal culture media,
      interleukin 10 increased the numbers of dendritic spines in addition to
      excitatory and inhibitory synapses. Interestingly, without external stimuli, the
      amount of interleukin 10 released from the intact microglia appeared to be
      sufficient for the induction of synaptic formation. The neutralizing antibodies
      of interleukin 10 receptors attenuated the induction of the synaptic formation by
      microglia. The expression of interleukin 10 receptor was newly found in the
      hippocampal neurons of early developmental stage. When interleukin 10 receptors
      on the hippocampal neurons were knocked down with specific shRNA, the induction
      of synaptic formation by microglia and interleukin 10 disappeared. Pretreatment
      with lipopolysaccharide inhibited microglia from inducing synaptic formation, and
      interleukin 1beta antagonized the induction of synaptic formation by interleukin
      10. In conclusion, the developing microglia regulated synaptic functions and
      neuronal development through the interactions of the interleukin 10 released from
      the microglia with interleukin 10 receptors expressed on the hippocampal neurons.

PMID- 24278398
TI  - Hybridization-based detection of Helicobacter pylori at human body temperature
      using advanced locked nucleic acid (LNA) probes.
AB  - The understanding of the human microbiome and its influence upon human life has
      long been a subject of study. Hence, methods that allow the direct detection and
      visualization of microorganisms and microbial consortia (e.g. biofilms) within
      the human body would be invaluable. In here, we assessed the possibility of
      developing a variant of fluorescence in situ hybridization (FISH), named
      fluorescence in vivo hybridization (FIVH), for the detection of Helicobacter
      pylori. Using oligonucleotide variations comprising locked nucleic acids (LNA)
      and 2'-O-methyl RNAs (2'OMe) with two types of backbone linkages (phosphate or
      phosphorothioate), we were able to successfully identify two probes that
      hybridize at 37  degrees C with high specificity and sensitivity for H. pylori,
      both in pure cultures and in gastric biopsies. Furthermore, the use of this type
      of probes implied that toxic compounds typically used in FISH were either found
      to be unnecessary or could be replaced by a non-toxic substitute. We show here
      for the first time that the use of advanced LNA probes in FIVH conditions
      provides an accurate, simple and fast method for H. pylori detection and
      location, which could be used in the future for potential in vivo applications
      either for this microorganism or for others.

PMID- 24278400
TI  - Detection of anorectal and cervicovaginal Chlamydia trachomatis infections
      following azithromycin treatment: prospective cohort study with multiple time
      sequential measures of rRNA, DNA, quantitative load and symptoms.
AB  - BACKGROUND: Determination of Chlamydia trachomatis (Ct) treatment success is
      hampered by current assessment methods, which involve a single post-treatment
      measurement only. Therefore, we evaluated Ct detection by applying multiple
      laboratory measures on time-sequential post-treatment samples. METHODS: A
      prospective cohort study was established with azithromycin-treated (1000 mg) Ct
      patients (44 cervicovaginal and 15 anorectal cases). Each patient provided 18
      self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%;
      1,016 samples). Samples were tested for 16S rRNA (TMA), bacterial load
      (quantitative PCR; Chlamydia plasmid DNA) and type (serovar and multilocus
      sequence typing). Covariates (including behavior, pre-treatment load, anatomic
      site, symptoms, age, and menstruation) were tested for their potential
      association with positivity and load at 3-8 weeks using regression analyses
      controlling for repeated measures. FINDINGS: By day 9, Ct positivity decreased to
      20% and the median load to 0.3 inclusion-forming units (IFU) per ml (pre
      treatment: 170 IFU/ml). Of the 35 cases who reported no sex, sex with a treated
      partner or safe sex with a new partner, 40% had detection, i.e. one or more
      positive samples from 3-8 weeks (same Ct type over time), indicating possible
      antimicrobial treatment failure. Cases showed intermittent positive detection and
      the number of positive samples was higher in anorectal cases than in
      cervicovaginal cases. The highest observed bacterial load between 3-8 weeks post
      treatment was 313 IFU/ml, yet the majority (65%) of positive samples showed a
      load of <= 2 IFU/ml. Pre-treatment load was found to be associated with later
      load in anorectal cases. CONCLUSIONS: A single test at 3-8 weeks post-treatment
      frequently misses Ct. Detection reveals intermittent low loads, with an unknown
      risk of later complications or transmission. These findings warrant critical re
      evaluation of the clinical management of single dose azithromycin-treated Ct
      patients and fuel the debate on defining treatment failure. Clinicaltrials.gov
      Identifier: NCT01448876.

PMID- 24278399
TI  - Objective measurement of daytime napping, cognitive dysfunction and subjective
      sleepiness in Parkinson's disease.
AB  - INTRODUCTION: Sleep-wake disturbances and concomitant cognitive dysfunction in
      Parkinson's disease (PD) contribute significantly to morbidity in patients and
      their carers. Subjectively reported daytime sleep disturbance is observed in over
      half of all patients with PD and has been linked to executive cognitive
      dysfunction. The current study used daytime actigraphy, a novel objective measure
      of napping and related this to neuropsychological performance in a sample of PD
      patients and healthy, age and gender-matched controls. Furthermore this study
      aimed to identify patients with PD who may benefit from pharmacologic and
      behavioural intervention to improve these symptoms. METHODS: Eighty-five PD
      patients and 21 healthy, age-matched controls completed 14 days of wrist
      actigraphy within two weeks of neuropsychological testing. Objective napping
      measures were derived from actigraphy using a standardised protocol and
      subjective daytime sleepiness was recorded by the previously validated Epworth
      Sleepiness Scale. RESULTS: Patients with PD had a 225% increase in the mean nap
      time per day (minutes) as recorded by actigraphy compared to age matched controls
      (39.2 +/- 35.2 vs. 11.5 +/- 11.0 minutes respectively, p < 0.001). Significantly,
      differences in napping duration between patients, as recorded by actigraphy were
      not distinguished by their ratings on the subjective measurement of excessive
      daytime sleepiness. Finally, those patients with excessive daytime napping showed
      greater cognitive deficits in the domains of attention, semantic verbal fluency
      and processing speed. CONCLUSION: This study confirms increased levels of napping
      in PD, a finding that is concordant with subjective reports. However, subjective
      self-report measures of excessive daytime sleepiness do not robustly identify
      excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in
      those patients who napped excessively. Furthermore, this study suggests that
      daytime actigraphy, a non-invasive and inexpensive objective measure of daytime
      sleep, can identify patients with PD who may benefit from pharmacologic and
      behavioural interventions to improve these symptoms.

PMID- 24278401
TI  - Identification of an evx1-dependent joint-formation pathway during FIN
      regeneration.
AB  - Joints are essential for skeletal flexibly and form, yet the process underlying
      joint morphogenesis is poorly understood. Zebrafish caudal fins are comprised of
      numerous segmented bony fin rays, where growth occurs by the sequential addition
      of new segments and new joints. Here, we evaluate joint gene expression during
      fin regeneration. First, we identify three genes that influence joint formation,
      evx1, dlx5a, and mmp9. We place these genes in a common molecular pathway by
      evaluating both their expression patterns along the distal-proximal axis (i.e.
      where the youngest tissue is always the most distal), and by evaluating changes
      in gene expression following gene knockdown. Prior studies from our lab indicate
      that the gap junction protein Cx43 suppresses joint formation. Remarkably,
      changes in Cx43 activity alter the expression of joint markers. For example, the
      reduced levels of Cx43 in the sof (b123) mutant causes short fin ray
      segments/premature joints. We also find that the expression of evx1-dlx5a-mmp9 is
      shifted distally in sof (b123) , consistent with premature expression of these
      genes. In contrast, increased Cx43 in the alf (dty86) mutant leads to stochastic
      joint failure and stochastic loss of evx1 expression. Indeed, reducing the level
      of Cx43 in alf (dty86) rescues both the evx1 expression and joint formation.
      These results suggest that Cx43 influences the pattern of joint formation by
      influencing the timing of evx1 expression. 

PMID- 24278402
TI  - Not all continuous dimensions map equally: number-brightness mapping in human
      infants.
AB  - Evidence for spontaneous mappings between the dimensions of number and length,
      time and length, and number and time, has been recently described in preverbal
      infants. It is unclear, however, whether these abilities reflect the existence of
      privileged mappings between certain quantitative dimensions, like number, space
      and time, or instead the existence of a magnitude system underlying the
      representation of any quantitative dimension, and allowing mappings across those
      dimensions. Four experiments, using the same methods from previous research that
      revealed a number-length mapping in eight-month-old infants, investigated whether
      infants of the same age establish mappings between number and a different, non
      spatial continuous dimension: level of brightness. We show that infants are able
      to learn and productively use mappings between brightness and number when they
      are positively related, i.e., larger numbers paired with brighter or higher
      contrast levels, and fail when they are inversely related, i.e., smaller numbers
      paired with brighter or higher contrast levels, suggesting that they are able to
      learn this mapping in a specific direction. However, infants not only do not show
      any baseline preference for any direction of the number-brightness mapping, but
      fail at transferring the discrimination from one dimension (number) to the other
      (brightness). Although infants can map multiple dimensions to one another, the
      number-length mapping may be privileged early in development, as it is for
      adults. 

PMID- 24278403
TI  - Caco-2 cell acquisition of dietary iron(III) invokes a nanoparticulate endocytic
      pathway.
AB  - Dietary non-heme iron contains ferrous [Fe(II)] and ferric [Fe(III)] iron
      fractions and the latter should hydrolyze, forming Fe(III) oxo-hydroxide
      particles, on passing from the acidic stomach to less acidic duodenum. Using
      conditions to mimic the in vivo hydrolytic environment we confirmed the formation
      of nanodisperse fine ferrihydrite-like particles. Synthetic analogues of these (~
      10 nm hydrodynamic diameter) were readily adherent to the cell membrane of
      differentiated Caco-2 cells and internalization was visualized using transmission
      electron microscopy. Moreover, Caco-2 exposure to these nanoparticles led to
      ferritin formation (i.e., iron utilization) by the cells, which, unlike for
      soluble forms of iron, was reduced (p=0.02) by inhibition of clathrin-mediated
      endocytosis. Simulated lysosomal digestion indicated that the nanoparticles are
      readily dissolved under mildly acidic conditions with the lysosomal ligand,
      citrate. This was confirmed in cell culture as monensin inhibited Caco-2
      utilization of iron from this source in a dose dependent fashion (p<0.05) whilet
      soluble iron was again unaffected. Our findings reveal the possibility of an
      endocytic pathway for acquisition of dietary Fe(III) by the small intestinal
      epithelium, which would complement the established DMT-1 pathway for soluble
      Fe(II). 

PMID- 24278404
TI  - Targeting of arenavirus RNA synthesis by a carboxamide-derivatized aromatic
      disulfide with virucidal activity.
AB  - Several arenaviruses can cause severe hemorrhagic fever (HF) in humans,
      representing a public health threat in endemic areas of Africa and South America.
      The present study characterizes the potent virucidal activity of the carboxamide
      derivatized aromatic disulfide NSC4492, an antiretroviral zinc finger-reactive
      compound, against Junin virus (JUNV), the causative agent of Argentine HF. The
      compound was able to inactivate JUNV in a time and temperature-dependent manner,
      producing more than 99 % reduction in virus titer upon incubation with virions at
      37  degrees C for 90 min. The ability of NSC4492-treated JUNV to go through
      different steps of the multiplication cycle was then evaluated. Inactivated
      virions were able to bind and enter into the host cell with similar efficiency as
      control infectious particles. In contrast, treatment with NSC4492 impaired the
      capacity of JUNV to drive viral RNA synthesis, as measured by quantitative RT
      PCR, and blocked viral protein expression, as determined by indirect
      immunofluorescence. These results suggest that the disulfide NSC4492 targets on
      the arenavirus replication complex leading to impairment in viral RNA synthesis.
      Additionally, analysis of VLP produced in NSC4492-treated cells expressing JUNV
      matrix Z protein revealed that the compound may interact with Z resulting in an
      altered aggregation behavior of this protein, but without affecting its intrinsic
      self-budding properties. The potential perspectives of NSC4492 as an inactivating
      vaccinal compound for pathogenic arenaviruses are discussed.

PMID- 24278405
TI  - A population-based nationwide cross-sectional study on preventive health services
      utilization in Portugal--what services (and frequencies) are deemed necessary by
      patients?
AB  - BACKGROUND: Most of the strategies to induce a more rational use of preventive
      health services are oriented to the medical side of the doctor-patient
      relationship. However, the consultation model has changed, and patients now have
      a more important role in medical consultation. The aim of this study was to
      assess which healthcare services are deemed necessary, and with what frequency,
      by adults from the general Portuguese population. METHODS:  DESIGN: Population
      based nationwide cross-sectional study Setting: Portuguese population
      Participants: One thousand Portuguese adults, surveyed by computer-assisted
      telephone interviewing and selected by a stratified cluster sampling design.
      MEASUREMENTS: Proportions and population prevalence estimates were determined for
      each healthcare service, taking into account whether respondents considered them
      necessary, and with what frequency. RESULTS: Respondent ages ranged between 18
      and 97 years, and 520 of 1000 (52%) respondents were women. Among Portuguese
      adults, 99.2% (95% confidence interval (CI): 98.5 to 99.6) believe that they
      should undergo general routine blood and urine tests, to be repeated every 12.0
      months on average (95% CI: 11.4 to 12.6); 87.4% (95% CI: 85.3 to 89.3) of the
      respondents reported having actually performed these tests. Of the 15 services
      surveyed, 14 were considered periodically necessary by more than 60% of
      respondents. Among the respondents, 37.7% (95% CI: 34.5 to 41.1) reported using
      healthcare services by their own initiative. CONCLUSIONS: The majority of
      Portuguese adults believe that they should utilize a great number of healthcare
      services, on a nearly annual basis; most actually follow this schedule. Our
      findings indicate a tendency towards the overuse of resources. Adequate patient
      oriented strategies regarding the use of medical tests and preventive
      interventions--with appropriate information and discussion of risks and harms-
      are urgently needed, and crucial for achieving a more rational use of healthcare
      services and for preventing the consequences of over-testing.

PMID- 24278406
TI  - Saponin 1 induces apoptosis and suppresses NF-kappaB-mediated survival signaling
      in glioblastoma multiforme (GBM).
AB  - Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a
      traditional Chinese medicine against rheumatism and phlebitis. It has also been
      shown to exhibit significant anti-tumor activity against human leukemia (HL-60
      cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated
      the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG
      cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell
      lines, with a 50% inhibitory concentration at 24 h of 7.4 ug/ml in U251MG cells
      and 8.6 ug/ml in U87MG cells, respectively. Nuclear fluorescent staining and
      electron microscopy showed that saponin 1 caused characteristic apoptotic
      morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also
      verified by DNA ladder electrophoresis and flow cytometry. Additionally,
      immunocytochemistry and western blotting analyses revealed a time-dependent
      decrease in the expression and nuclear location of NF-kappaB following saponin 1
      treatment. Western blotting data indicated a significant decreased expression of
      inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin
      1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated
      apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These
      findings indicate that saponin 1 inhibits cell growth of GBM cells at least
      partially by inducing apoptosis and inhibiting survival signaling mediated by NF
      kappaB. In addition, in vivo study also demonstrated an obvious inhibition of
      saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced
      xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non
      neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in
      vitro and in vivo anti-tumor efficacy and merits further investigation as a
      potential therapeutic agent for GBM. 

PMID- 24278407
TI  - Effects of metformin on CD133+ colorectal cancer cells in diabetic patients.
AB  - In diabetic patients complicated with colorectal cancer (CRC), metformin
      treatment was reported to have diverse correlation with CRC-specific mortality.
      In laboratory studies, metformin was reported to affect the survival of cancer
      stem cells (CSCs) in breast and pancreatic cancers and glioblastoma. Although
      cscs play a critical role in the resistance to 5-fluorouracil (5-FU) chemotherapy
      in CRC patients, the effect of metformin on cscs in CRC patients and the
      synergistic effect of metformin in combination with 5-FU on cscs are not
      reported. In the present study pathological examinations were performed in 86 CRC
      patients complicated with type 2 DM who had been divided into a metformin group
      and a non-metformin group. Comparisons regarding pathological type, incidence of
      metastasis, expression of CD133 and beta-catenin were conducted between the two
      groups. We explored the synergistic effects of metformin in combination with 5-FU
      on the proliferation, cell cycle, apoptosis and the proportion of CD133+ cscs of
      SW620 human colorectal cancer cell lines. The results show that metformin
      treatment had reverse correlations with the proportion of patients with poorly
      differentiated adenocarcinoma, the proportion of CD133+ cscs in CRC patients with
      type 2 DM. Metformin enhanced the antiproliferative effects of 5-FU on CD133+
      cscs in SW620 cells. These findings provide an important complement to previous
      study. Inhibition of the proliferation of CD133+ cscs may be a potential
      mechanism responsible for the association of metformin use with improved CRC
      outcomes in CRC patients with type 2 diabetes. 

PMID- 24278409
TI  - Earthworms produce phytochelatins in response to arsenic.
AB  - Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft
      metal and metalloid ions, such as cadmium and arsenic. They are widely produced
      by plants and microbes; phytochelatin synthase genes are also present in animal
      species from several different phyla, but there is still little known about
      whether these genes are functional in animals, and if so, whether they are metal
      responsive. We analysed phytochelatin production by direct chemical analysis in
      Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found
      that arsenic clearly induced phytochelatin production in a dose-dependent manner.
      It was necessary to measure the phytochelatin metabolite concentrations directly,
      as there was no upregulation of phytochelatin synthase gene expression after 28
      days: phytochelatin synthesis appears not to be transcriptionally regulated in
      animals. A further untargetted metabolomic analysis also found changes in
      metabolites associated with the transsulfuration pathway, which channels sulfur
      flux from methionine for phytochelatin synthesis. There was no evidence of
      biological transformation of arsenic (e.g. into methylated species) as a result
      of laboratory arsenic exposure. Finally, we compared wild populations of
      earthworms sampled from the field, and found that both arsenic-contaminated and
      cadmium-contaminated mine site worms had elevated phytochelatin concentrations. 

PMID- 24278410
TI  - Odorous and non-fatal skin secretion of adult wrinkled frog (Rana rugosa) is
      effective in avoiding predation by snakes.
AB  - The roles played by nonfatal secretions of adult anurans in the avoidance of
      predation remain unknown. The adult Wrinkled frog (Rana rugosa) has warty skin
      with the odorous mucus secretion that is not fatal to the snake Elaphe
      quadrivirgata. We fed R. rugosa or Fejervarya limnocharis, which resembles R.
      rugosa in appearance and has mucus secretion, to snakes and compared the snakes'
      responses to the frogs. Compared to F. limnocharis, R. rugosa was less frequently
      bitten or swallowed by snakes. The snakes that bit R. rugosa spat out the frogs
      and showed mouth opening (gaping) behavior, while the snakes that bit F.
      limnocharis did not show gaping behavior. We also compared the responses of the
      snakes to R. rugosa and F. limnocharis secretions. We coated palatable R.
      japonica with secretions from R. rugosa or F. limnocharis. The frogs coated by R.
      rugosa secretion were less frequently bitten or swallowed than those coated by F.
      limnocharis secretion. We concluded that compared to different frog species of
      similar sizes, the adult R. rugosa was less frequently preyed upon by, and that
      its skin secretion was effective in avoiding predation by snakes. 

PMID- 24278408
TI  - LOV takes a pick: thermodynamic and structural aspects of the flavin-LOV
      interaction of the blue-light sensitive photoreceptor YtvA from Bacillus
      subtilis.
AB  - LOV domains act as versatile photochromic switches servicing multiple effector
      domains in a variety of blue light sensing photoreceptors abundant in a multitude
      of organisms from all kingdoms of life. The perception of light is realized by a
      flavin chromophore that upon illumination reversibly switches from the non
      covalently bound dark-state to a covalently linked flavin-LOV adduct. It is
      usually assumed that most LOV domains preferably bind FMN, but heterologous
      expression frequently results in the incorporation of all natural occurring
      flavins, i.e. riboflavin, FMN and FAD. Over recent years, the structures,
      photochemical properties, activation mechanisms and physiological functions of a
      multitude of LOV proteins have been studied intensively, but little is known
      about its affinities to physiologically relevant flavins or the thermodynamics of
      the flavin-LOV interaction. We have investigated the interaction of the LOV
      domain of the well characterized bacterial photoreceptor YtvA with riboflavin,
      FMN and FAD by ITC experiments providing binding constants and thermodynamic
      profiles of these interactions. For this purpose, we have developed a protocol
      for the production of the apo forms of YtvA and its isolated LOV domain and we
      demonstrate that the latter can be used as a molecular probe for free flavins in
      cell lysates. Furthermore, we show here using NMR spectroscopic techniques and
      Analytical Ultracentrifugation that the flavin moiety stabilizes the conformation
      of the LOV domain and that dimerization of YtvA is caused not only by
      intermolecular LOV-LOV but also by STAS-STAS contacts. 

PMID- 24278411
TI  - Identification of a novel subpopulation of tumor-initiating cells from
      gemcitabine-resistant pancreatic ductal adenocarcinoma patients.
AB  - Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy.
      Although there are many reports using pancreatic cancer cells derived from
      patients who did not receive chemotherapy, characteristics of pancreatic cancer
      cells from chemotherapy-resistant patients remain unclear. In this study, we set
      out to establish a cancer cell line in disseminated cancer cells derived from
      gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in
      vitro co-culture system with stromal cells, we established a novel pancreatic
      tumor-initiating cell line. The cell line required its direct interaction with
      stromal cells for its in vitro clonogenic growth and passaging. Their direct
      interaction induced basal lamina-like extracellular matrix formation that
      maintained colony formation. The cell line expressed CD133 protein, which
      expression level changed autonomously and by culture conditions. These results
      demonstrated that there were novel pancreatic tumor-initiating cells that
      required direct interactions with stromal cells for their in vitro cultivation in
      gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help
      to develop novel therapies that enhance effects of gemcitabine or novel anti
      cancer drugs. 

PMID- 24278412
TI  - Influence of developmental conditions on immune function and dispersal-related
      traits in the Glanville fritillary (Melitaea cinxia) butterfly.
AB  - Organisms in the wild are constantly faced with a wide range of environmental
      variability, such as fluctuation in food availability. Poor nutritional
      conditions influence life-histories via individual resource allocation patterns,
      and trade-offs between competing traits. In this study, we assessed the influence
      of food restriction during development on the energetically expensive traits
      flight metabolic rate (proxy of dispersal ability), encapsulation rate (proxy of
      immune defence), and lifespan using the Glanville fritillary butterfly, Melitaea
      cinxia, as a model organism. Additionally, we examined the direct costs of flight
      on individual immune function, and whether those costs increase under restricted
      environmental conditions. We found that nutritional restriction during
      development enhanced adult encapsulations rate, but reduced both resting and
      flight metabolic rates. However, at the individual level metabolic rates were not
      associated with encapsulation rate. Interestingly, individuals that were forced
      to fly prior to the immune assays had higher encapsulation rates than individuals
      that had not flown, suggesting that flying itself enhances immune response.
      Finally, in the control group encapsulation rate correlated positively with
      lifespan, whereas in the nutritional restriction group there was no relationship
      between these traits, suggesting that the association between encapsulation rate
      on adult lifespan was condition-dependent. Thus stressful events during both
      larval development (food limitation) and adulthood (forced flight) induce
      increased immune response in the adult butterflies, which may allow individuals
      to cope with stressful events later on in life. 

PMID- 24278414
TI  - Streptococcal SpeB cleaved PAR-1 suppresses ERK phosphorylation and blunts
      thrombin-induced platelet aggregation.
AB  - BACKGROUND: The family of 4 related protease-activated receptors (PAR-1, 2, 3 &
      4) expressed by mammalian cells allow to sense for and react to extracellular
      proteolytic activity. Since major human bacterial pathogens secret a wide array
      of protease(-s) we investigated whether they interfere with human PAR function.
      METHODOLOGY/PRINCIPAL FINDINGS: Supernatants from cultures of major human
      bacterial pathogens were assayed for the presence of protease(-s) capable to
      cleave overexpressed human PAR-1, 2, 3 and 4 reporter constructs. Group A
      streptococcus (GAS) was found to secret a PAR-1-cleaving protease. Experiments
      involving genetical and pharmacological gain and loss of function identified
      streptococcal pyrogenic exotoxin B SpeB as the protease responsible. On the
      host's side analysis of overexpressed PAR-1 carrying alanine substitutions and
      deletions showed the amino acid residue leucine44 on PAR-1's extracellular N
      terminus to be the only cleavage site. Complementary studies on endogenously
      expressed PAR-1 using PAR-1 blocking antibodies further supported our conclusion.
      Through PAR-1 cleavage SpeB efficiently blunted thrombin-induced induction of the
      ERK-pathway in endothelial cells and prevented platelets aggregation in response
      to thrombin. CONCLUSIONS/SIGNIFICANCE: Our results identify a novel function of
      the streptococcal virulence factor SpeB. By cleaving human PAR-1 at the N
      terminal amino acid residue leucine44 SpeB rendered endothelial cells
      unresponsive to thrombin and prevented human platelets from thrombin-induced
      aggregation. These results suggest that by blunting PAR-1 signaling, SpeB
      modulates various innate host responses directed against invasive GAS potentially
      helping the invasive bacteria to escape. This may allow to tailor additional
      treatments in the future since upon invasion of the blood stream endothelial
      cells as well as platelets and mononuclear cells respond to PAR-1 agonists aiming
      to prevent further bacterial dissemination.

PMID- 24278413
TI  - Decreased autophagy in rat heart induced by anti-beta1-adrenergic receptor
      autoantibodies contributes to the decline in mitochondrial membrane potential.
AB  - It has been recognized that changes in mitochondrial structure plays a key role
      in development of cardiac dysfunction, and autophagy has been shown to exert
      maintenance of mitochondrial homeostasis effects. Our previous study found that
      anti-beta1-adrenergic receptor autoantibodies (beta1-AABs) could lead to cardiac
      dysfunction along with abnormalities in mitochondrial structure. The present
      study tested the hypothesis that beta1-AABs may induce the decline in
      mitochondrial membrane potential (DeltaPsim) by suppression of cardiac autophagy,
      which contributed to cardiac dysfunction. Male adult rats were randomized to
      receive a vehicle or peptide corresponding to the second extracellular loop of
      the beta1 adrenergic receptor (beta1-AAB group, 0.4 MUg/g every two weeks for 12
      weeks) and treated with rapamycin (RAPA, an autophagy agonist) at 5 mg/kg/day for
      two days before detection. At the 4th week, 8th week and 12th week of active
      immunization, the rats were sacrificed and cardiac function and the levels of
      cardiac LC3 and Beclin-1 were detected. DeltaPsim in cardiac myocytes was
      determined by myocardial radionuclide imaging technology and JC-1 staining. In
      the present study, beta1-AABs caused cardiac dysfunction, reduced DeltaPsim and
      decreased cardiac autophagy. Treatment with RAPA markedly attenuated beta1-AABs
      induced cardiac injury evidenced by recovered DeltaPsim. Taken together, these
      results suggested that beta1-AABs exerted significant decreased DeltaPsim, which
      may contribute to cardiac dysfunction, most likely by decreasing cardiac
      autophagy in vivo. Moreover, myocardial radionuclide imaging technology may be
      needed to assess the risk in developing cardiac dysfunction for the people who
      have beta1-AABs in their blood. 

PMID- 24278415
TI  - Modified uterine allotransplantation and immunosuppression procedure in the sheep
      model.
AB  - OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation
      technique and an effective immunosuppressive protocol in the sheep model.
      METHODS: In this pilot study, 10 sexually mature ewes were subjected to
      laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus
      allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis
      was performed using continuous, non-interlocking sutures. Complete tissue
      reperfusion was achieved in all animals within 30 s after the vascular re
      anastomosis, without any evidence of arterial or venous thrombosis. The
      immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and
      methylprednisolone tablets. Graft viability was assessed by transrectal
      ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.
      RESULTS: Viable uterine tissue and vascular patency were observed on transrectal
      ultrasonography and second-look laparotomy. Histological analysis of the graft
      tissue (performed in one ewe) revealed normal tissue architecture with a very
      subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have
      developed a modified procedure that allowed us to successfully perform
      orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and
      vascular anatomy (apart from the bicornuate uterus) is similar to the human
      anatomy, making the ovine model excellent for human uterine transplant research.

PMID- 24278417
TI  - The environment, not space, dominantly structures the landscape patterns of the
      richness and composition of the tropical understory vegetation.
AB  - The mechanisms driving the spatial patterns of species richness and composition
      are essential to the understanding of biodiversity. Numerous studies separately
      identify the contributions of the environment (niche process) and space (neutral
      process) to the species richness or composition at different scales, but few
      studies have investigated the contributions of both types of processes in the two
      types of data at the landscape scale. In this study, we partitioned the spatial
      variations in all, exotic and native understory plant species richness and
      composition constrained by environmental variables and space in 134 plots that
      were spread across 10 counties in Hainan Island in southern China. The 134 plots
      included 70 rubber (Hevea brasiliensis) plantation plots, 50 eucalyptus
      (Eucalyptus urophylla) plantation plots, and 14 secondary forest plots. RDA based
      variation partitioning was run to assess the contribution of environment and
      space to species richness and composition. The results showed that the
      environmental variables alone explained a large proportion of the variations in
      both the species richness and composition of all, native, and exotic species. The
      RDA results indicated that overstory composition (forest type here) plays a
      leading role in determining species richness and composition patterns. The alpha
      and beta diversities of the secondary forest plots were markedly higher than that
      of the two plantations. In conclusion, niche differentiation processes are the
      principal mechanisms that shape the alpha and beta diversities of understory
      plant species in Hainan Island. 

PMID- 24278416
TI  - Affinity purification of human factor H on polypeptides derived from
      streptococcal m protein: enrichment of the Y402 variant.
AB  - Recent studies indicate that defective activity of complement factor H (FH) is
      associated with several human diseases, suggesting that pure FH may be used for
      therapy. Here, we describe a simple method to isolate human FH, based on the
      specific interaction between FH and the hypervariable region (HVR) of certain
      Streptococcus pyogenes M proteins. Special interest was focused on the FH
      polymorphism Y402H, which is associated with the common eye disease age-related
      macular degeneration (AMD) and has also been implicated in the binding to M
      protein. Using a fusion protein containing two copies of the M5-HVR, we found
      that the Y402 and H402 variants of FH could be efficiently purified by single
      step affinity chromatography from human serum containing the corresponding
      protein. Different M proteins vary in their binding properties, and the M6 and M5
      proteins, but not the M18 protein, showed selective binding of the FH Y402
      variant. Accordingly, chromatography on a fusion protein derived from the M6-HVR
      allowed enrichment of the Y402 protein from serum containing both variants. Thus,
      the exquisite binding specificity of a bacterial protein can be exploited to
      develop a simple and robust procedure to purify FH and to enrich for the FH
      variant that protects against AMD. 

PMID- 24278418
TI  - Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced
      aggregate formation.
AB  - In polyglutamine diseases, an abnormally elongated polyglutamine results in
      protein misfolding and accumulation of intracellular aggregates. Autophagy is a
      major cellular degradative pathway responsible for eliminating unnecessary
      proteins, including polyglutamine aggregates. Basal autophagy constitutively
      occurs at low levels in cells for the performance of homeostatic function, but
      the regulatory mechanism for basal autophagy remains elusive. Here we show that
      the Na(+)/H(+) exchanger (NHE) family of ion transporters affect autophagy in a
      neuron-like cell line (Neuro-2a cells). We showed that expression of NHE1 and
      NHE5 is correlated to polyglutamine accumulation levels in a cellular model of
      Huntington's disease, a fatal neurodegenerative disorder characterized by
      accumulation of polyglutamine-containing aggregate formation in the brain.
      Furthermore, we showed that loss of NHE5 results in increased polyglutamine
      accumulation in an animal model of Huntington's disease. Our data suggest that
      cellular pH regulation by NHE1 and NHE5 plays a role in regulating basal
      autophagy and thereby promotes autophagy-mediated degradation of proteins
      including polyglutamine aggregates. 

PMID- 24278419
TI  - A new method for quantitative immunoblotting of endogenous alpha-synuclein.
AB  - beta-Sheet-rich aggregates of alpha-synuclein (alphaSyn) are the hallmark
      neuropathology of Parkinson's disease and related synucleinopathies, whereas the
      principal native structure of alphaSyn in healthy cells--unfolded monomer or
      alpha-helically folded oligomer--is under debate. Our recent crosslinking
      analysis of alphaSyn in intact cells showed that a large portion of endogenous
      alphaSyn can be trapped as oligomers, most notably as apparent tetramers. One
      challenge in such studies is accurately quantifying alphaSyn Western blot signals
      among samples, as crosslinked alphaSyn trends toward increased immunoreactivity.
      Here, we analyzed this phenomenon in detail and found that treatment with the
      reducible amine-reactive crosslinker DSP strongly increased alphaSyn
      immunoreactivity even after cleavage with the reducing agent beta
      mercaptoethanol. The effect was observed with all alphaSyn antibodies tested and
      in all sample types from human brain homogenates to untransfected neuroblastoma
      cells, permitting easy detection of endogenous alphaSyn in the latter, which had
      long been considered impossible. Coomassie staining of blots before and after
      several hours of washing revealed complete retention of alphaSyn after DSP/beta
      mercaptoethanol treatment, in contrast to a marked loss of alphaSyn without this
      treatment. The treatment also enhanced immunodetection of the homologs beta- and
      gamma-synuclein and of histones, another group of small, lysine-rich proteins. We
      conclude that by neutralizing positive charges and increasing protein
      hydrophobicity, amine crosslinker treatment promotes adhesion of alphaSyn to
      blotting membranes. These data help explain the recent report of fixing alphaSyn
      blots with paraformaldehyde after transfer, which we find produces similar but
      weaker effects. DSP/beta-mercaptoethanol treatment of Western blots should be
      particularly useful to quantify low-abundance alphaSyn forms such as
      extracellular and post-translationally modified alphaSyn and splice variants.

PMID- 24278420
TI  - A multi-antigenic adenoviral-vectored vaccine improves BCG-induced protection of
      goats against pulmonary tuberculosis infection and prevents disease progression.
AB  - The "One world, one health" initiative emphasizes the need for new strategies to
      control human and animal tuberculosis (TB) based on their shared interface. A
      good example would be the development of novel universal vaccines against
      Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat
      model, a natural TB host, to assess the protective effectiveness of a new vaccine
      candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty
      three goat kids were divided in three groups: Group 1) vaccinated with BCG (week
      0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant
      adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF),
      and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a
      low dose of M. caprae was performed (week 15). After necropsy (week 28), the
      pulmonary gross pathology was quantified using high resolution Computed
      Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also
      evaluated through a comprehensive qualitative histopathological analysis. M.
      caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the
      effects of BCG reducing gross lesion volume and bacterial load, as well as
      increasing weight gain. The number of Ag85A-specific gamma interferon-producing
      memory T-cells was identified as a predictor of vaccine efficacy. Specific
      cellular and humoral responses were measured throughout the 13-week post
      challenge period, and correlated with the severity of lesions. Unvaccinated goats
      exhibited the typical pathological features of active TB in humans and domestic
      ruminants, while vaccinated goats showed only very small lesions. The data
      presented in this study indicate that multi-antigenic adenoviral vectored
      vaccines boosts protection conferred by vaccination with BCG. 

PMID- 24278421
TI  - Circulating levels of fatty acid-binding protein family and metabolic phenotype
      in the general population.
AB  - OBJECTIVE: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa
      proteins, and some FABPs have been to be used as biomarkers of tissue injury by
      leak from cells. However, recent studies have shown that FABPs can be secreted
      from cells into circulation. Here we examined determinants and roles of
      circulating FABPs in a general population. METHODS: From the database of the
      Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011
      for 296 subjects on no medication were retrieved, and FABP1~5 in their serum
      samples were assayed. RESULTS: Level of FABP4, but not the other isoforms, showed
      a gender difference, being higher in females than in males. Levels of all FABPs
      were negatively correlated with estimated glomerular filtration rate (eGFR), but
      a distinct pattern of correlation with other clinical parameters was observed for
      each FABP isoform; significant correlates were alanine aminotransferase (ALT),
      blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides
      eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP,
      BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for
      FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most
      strongly related to metabolic markers among FABPs. In a multivariate regression
      analysis, FABP4 level was an independent predictor of HOMA-R after adjustment of
      age, gender, WC, BP, HDL cholesterol, and hsCRP. CONCLUSIONS: Each FABP isoform
      level showed a distinct pattern of correlation with clinical parameters, although
      levels of all FABPs were negatively determined by renal function. Circulating
      FABP4 appears to be a useful biomarker for detecting pre-clinical stage of
      metabolic syndrome, especially insulin resistance, in the general population.

PMID- 24278422
TI  - Investigating the allosteric regulation of YfiN from Pseudomonas aeruginosa:
      clues from the structure of the catalytic domain.
AB  - Pseudomonas aeruginosa is responsible for a plethora of biofilm mediated chronic
      infections among which cystic fibrosis pneumonia is the most frightening. The
      long-term survival strategy of P. aeruginosa in the patients lungs is based on a
      fine balance of virulence vs dormant states and on genetic adaptation, in order
      to select persistent phenotypes as the small colony variants (SCVs), which
      strongly correlate with antibiotic resistance and poor lung function. Recent
      studies have coupled SCV with increased levels of the signaling molecule cyclic
      di-GMP, and demonstrated the central role of the diguanylate cyclase YfiN, part
      of the tripartite signaling module YifBNR, in c-di-GMP dependent SCV regulation.
      YfiN, also called TpbB, is a multi-domain membrane enzyme connecting periplasmic
      stimuli to cytosolic c-di-GMP production by an allosteric inside-out signaling
      mechanism that, due to the lack of structural data, is still largely
      hypothetical. We have solved the crystal structure of the catalytic domain
      (GGDEF), and measured the enzymatic activity of the cytosolic portion in real
      time by means of a newly developed method. Based on these results we demonstrate
      that, unlike other diguanylate cyclase, YfiN does not undergo product feedback
      inhibition, and that the presence of the HAMP domain is required for dimerization
      and catalysis. Coupling our structural and kinetic data with an in silico study
      we are now able to propose a model for the allosteric regulation of YfiN. 

PMID- 24278423
TI  - An attempt to detect siRNA-mediated genomic DNA modification by artificially
      induced mismatch siRNA in Arabidopsis.
AB  - Although tremendous progress has been made in recent years in identifying
      molecular mechanisms of small interfering RNA (siRNA) functions in higher plants,
      the possibility of direct interaction between genomic DNA and siRNA remains an
      enigma. Such an interaction was proposed in the 'RNA cache' hypothesis, in which
      a mutant allele is restored based on template-directed gene conversion. To test
      this hypothesis, we generated transgenic Arabidopsis thaliana plants
      conditionally expressing a hairpin dsRNA construct of a mutated acetolactate
      synthase (mALS) gene coding sequence, which confers chlorsulfuron resistance, in
      the presence of dexamethasone (DEX). In the transgenic plants, suppression of the
      endogenous ALS mRNA expression as well as 21-nt mALS siRNA expression was
      detected after DEX treatment. After screening >100,000 progeny of the mALS siRNA
      induced plants, no chlorsulfuron-resistant progeny were obtained. Further
      experiments using transgenic calli also showed that DEX-induced expression of
      mALS siRNA did not affect the number of chlorsulfuron-resistant calli. No trace
      of cytosine methylation of the genomic ALS region corresponding to the dsRNA
      region was observed in the DEX-treated calli. These results do not necessarily
      disprove the 'RNA cache' hypothesis, but indicate that an RNAi machinery for ALS
      mRNA suppression does not alter the ALS locus, either genetically or
      epigenetically. 

PMID- 24278424
TI  - Distal C terminus of CaV1.2 channels plays a crucial role in the neural
      differentiation of dental pulp stem cells.
AB  - L-type voltage-dependent CaV1.2 channels play an important role in the
      maintenance of intracellular calcium homeostasis, and influence multiple cellular
      processes. C-terminal cleavage of CaV1.2 channels was reported in several types
      of excitable cells, but its expression and possible roles in non-excitable cells
      is still not clear. The aim of this study was to determine whether distal C
      terminal fragment of CaV1.2 channels is present in rat dental pulp stem cells and
      its possible role in the neural differentiation of rat dental pulp stem cells. We
      generated stable CaV1.2 knockdown cells via short hairpin RNA (shRNA). Rat dental
      pulp stem cells with deleted distal C-terminal of CaV1.2 channels lost the
      potential of differentiation to neural cells. Re-expression of distal C-terminal
      of CaV1.2 rescued the effect of knocking down the endogenous CaV1.2 on the neural
      differentiation of rat dental pulp stem cells, indicating that the distal C
      terminal of CaV1.2 is required for neural differentiation of rat dental pulp stem
      cells. These results provide new insights into the role of voltage-gated Ca(2+)
      channels in stem cells during differentiation. 

PMID- 24278425
TI  - Enhanced detection of tuberculous mycobacteria in animal tissues using a semi
      nested probe-based real-time PCR.
AB  - Bovine tuberculosis has been tackled for decades by costly eradication programs
      in most developed countries, involving the laboratory testing of tissue samples
      from allegedly infected animals for detection of Mycobacterium tuberculosis
      complex (MTC) members, namely Mycobacterium bovis. Definitive diagnosis is
      usually achieved by bacteriological culture, which may take up to 6-12 weeks,
      during which the suspect animal carcass and herd are under sanitary arrest. In
      this work, a user-friendly DNA extraction protocol adapted for tissues was
      coupled with an IS6110-targeted semi-nested duplex real-time PCR assay to enhance
      the direct detection of MTC bacteria in animal specimens, reducing the time to
      achieve a diagnosis and, thus, potentially limiting the herd restriction period.
      The duplex use of a novel beta-actin gene targeted probe, with complementary
      targets in most mammals, allowed the assessment of amplification inhibitors in
      the tissue samples. The assay was evaluated with a group of 128 fresh tissue
      specimens collected from bovines, wild boars, deer and foxes. Mycobacterium bovis
      was cultured from 57 of these samples. Overall, the full test performance
      corresponds to a diagnostic sensitivity and specificity of 98.2% (CIP95% 89.4
      99.9%) and 88.7% (CIP95% 78.5-94.7%), respectively. An observed kappa coefficient
      was estimated in 0.859 (CI P95% 0.771-0.948) for the overall agreement between
      the semi-nested PCR assay and the bacteriological culture. Considering only
      bovine samples (n = 69), the diagnostic sensitivity and specificity were
      estimated in 100% (CIP95% 84.0-100%) and 97.7% (CIP95% 86.2-99.9%), respectively.
      Eight negative culture samples exhibiting TB-like lesions were detected by the
      semi-nested real-time PCR, thus emphasizing the increased potential of this
      molecular approach to detect MTC-infected animal tissues. This novel IS6110
      targeted assay allows the fast detection of tuberculous mycobacteria in animal
      specimens with very high sensitivity and specificity, being amenable and cost
      effective for use in the routine veterinary diagnostic laboratory with further
      automation possibilities.

PMID- 24278426
TI  - Expansion of the Spinocerebellar ataxia type 10 (SCA10) repeat in a patient with
      Sioux Native American ancestry.
AB  - Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia,
      is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the
      ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with
      ancestral ties to Latin American countries. Here, we report on a SCA10 patient
      with Sioux Native American ancestry and no reported Hispanic or Latino heritage.
      Neurological exam findings revealed impaired gait with mild, age-consistent
      cerebellar atrophy and no evidence of epileptic seizures. The age at onset for
      this patient, at 83 years of age, is the latest documented for SCA10 patients and
      is suggestive of a reduced penetrance allele in his family. Southern blot
      analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs
      surrounding the SCA10 locus showed a disease haplotype consistent with the
      previously described "SCA10 haplotype". This case suggests that the SCA10
      expansion represents an early mutation event that possibly occurred during the
      initial peopling of the Americas. 

PMID- 24278427
TI  - Pressureless mechanical induction of stem cell differentiation is dose and
      frequency dependent.
AB  - Movement is a key characteristic of higher organisms. During mammalian
      embryogenesis fetal movements have been found critical to normal tissue
      development. On the single cell level, however, our current understanding of stem
      cell differentiation concentrates on inducing factors through cytokine mediated
      biochemical signaling. In this study, human mesenchymal stem cells and
      chondrogenesis were investigated as representative examples. We show that
      pressureless, soft mechanical stimulation precipitated by the cyclic deformation
      of soft, magnetic hydrogel scaffolds with an external magnetic field, can induce
      chondrogenesis in mesenchymal stem cells without any additional chondrogenesis
      transcription factors (TGF-beta1 and dexamethasone). A systematic study on the
      role of movement frequency revealed a classical dose-response relationship for
      human mesenchymal stem cells differentiation towards cartilage using mere
      mechanical stimulation. This effect could even be synergistically amplified when
      exogenous chondrogenic factors and movement were combined. 

PMID- 24278428
TI  - Contrasting patterns of genetic differentiation among Blackcaps (Sylvia
      atricapilla) with divergent migratory orientations in Europe.
AB  - Migratory divides are thought to facilitate behavioral, ecological, and genetic
      divergence among populations with different migratory routes. However, it is
      currently contentious how much genetic divergence is needed to maintain distinct
      migratory behavior across migratory divides. Here we investigate patterns of
      neutral genetic differentiation among Blackcap (Sylvia atricapilla) populations
      with different migratory strategies across Europe. We compare the level of
      genetic divergence of populations migrating to southwestern (SW) or southeastern
      (SE) wintering areas with birds wintering in the British Isles following a
      recently established northwesterly (NW) migration route. The migratory divide
      between SW and SE wintering areas can be interpreted as a result of a re
      colonization process after the last glaciation. Thus we predicted greater levels
      of genetic differentiation among the SW/SE populations. However, a lack of
      genetic differentiation was found between SW and SE populations, suggesting that
      interbreeding likely occurs among Blackcaps with different migratory orientations
      across a large area; therefore the SW/SE migratory divide can be seen as diffuse,
      broad band and is, at best, a weak isolating barrier. Conversely, weak, albeit
      significant genetic differentiation was evident between NW and SW migrants
      breeding sympatrically in southern Germany, suggesting a stronger isolating
      mechanism may be acting in this population. Populations located within/near the
      SW/SE contact zone were the least genetically divergent from NW migrants,
      confirming NW migrants likely originated from within the contact zone.
      Significant isolation-by-distance was found among eastern Blackcap populations
      (i.e. SE migrants), but not among western populations (i.e. NW and SW migrants),
      revealing different patterns of genetic divergence among Blackcap populations in
      Europe. We discuss possible explanations for the genetic structure of European
      Blackcaps and how gene flow influences the persistence of divergent migratory
      behaviors. 

PMID- 24278429
TI  - Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage
      activation.
AB  - Idiopathic pulmonary fibrosis is characterized by abundant collagen production
      and accumulation of alternatively activated macrophages (M2) in the lower
      respiratory tract. Mechanisms as to how alveolar macrophages are activated by
      collagen breakdown products are unknown. Alveolar macrophages were obtained by
      bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF)
      and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of
      collagen type I, III, IV and V monomers w/wo a neutralizing antibody against
      scavenger receptor I class A (CD204). Culture supernatants were assayed for the
      M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra) by ELISA.
      Furthermore, expression of phospho-Akt was measured using ELISA and expression of
      CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III
      monomers significantly up-regulated CCL18, IL-1ra production of alveolar
      macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by
      collagen type I exposure. In addition, collagen type I stimulation increased
      pospho-Akt expression. Collagen type I effects were abrogated by neutralizing
      antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor
      (LY294002). Spontaneous CD204 expression of alveolar macrophages was
      significantly increased in patients with IPF. In conclusion, our findings
      demonstrate that monomeric collagen type I via CD204 induces phospho-Akt
      expression shifting alveolar macrophages to the profibrotic M2 type. Innate
      immune responses induced by collagen monomers might perpetuate pulmonary
      fibrosis. 

PMID- 24278430
TI  - Association between GRIN3A gene polymorphism in Kawasaki disease and coronary
      artery aneurysms in Taiwanese children.
AB  - Kawasaki disease (KD) is pediatric systemic vasculitis with the classic
      complication of coronary artery aneurysm (CAA). It is the leading cause of
      acquired cardiovascular diseases in children. Some severe cases present with
      multi-organ involvement or neurological dysfunction. To identify the role of the
      glutamate receptor, ionotropic, N-methyl-d-aspartate 3A (GRIN3A) in KD, we
      investigated genetic variations in GRIN3A in a Taiwanese cohort of 262 KD
      patients (76 with and 186 without CAA complications). We used univariate and
      multivariate regression analyses to identify the associations between clinical
      characteristics and GRIN3A genetic variations in KD. According to univariate
      regression analysis, CAA formation in KD was significantly associated with fever
      duration (p < 0.0001), first Intravenous immunoglobulin (IVIG) used (days after
      day one of fever) (p < 0.0001), and the GRIN3A (rs7849782) genetic variant (p <
      0.001). KD patients with GG+GC genotype showed a lower rate of developing CAA
      (GG+GC genotype: odds ratio = 0.26; 95% CI = 0.14-0.46). Significant associations
      were identified between KD with CAA complication and the GRIN3A (rs7849782)
      genetic variant by using multivariate regression analysis. Specifically,
      significant correlations were observed between KD with CAA complications and the
      presence of GG+GC genotypes for the GRIN3A rs7849782 single-nucleotide
      polymorphism (full model: odds ratio = 0.25; 95% CI = 0.14-0.46). Our results
      suggest that a polymorphism of the GRIN3A gene may play a role in KD
      pathogenesis. 

PMID- 24278431
TI  - Coordinate nuclear targeting of the FANCD2 and FANCI proteins via a FANCD2
      nuclear localization signal.
AB  - Fanconi anemia (FA) is a rare recessive disease, characterized by congenital
      defects, bone marrow failure, and increased cancer susceptibility. FA is caused
      by biallelic mutation of any one of sixteen genes. The protein products of these
      genes function cooperatively in the FA-BRCA pathway to repair DNA interstrand
      crosslinks (ICLs). A central step in the activation of this pathway is the
      monoubiquitination of the FANCD2 and FANCI proteins. Monoubiquitinated FANCD2 and
      FANCI localize to discrete chromatin regions where they function in ICL repair.
      Despite their critical role in ICL repair, very little is known about the
      structure, function, and regulation of the FANCD2 and FANCI proteins, or how they
      are targeted to the nucleus and chromatin. In this study, we describe the
      functional characterization of an amino-terminal FANCD2 nuclear localization
      signal (NLS). We demonstrate that the amino terminal 58 amino acids of FANCD2 can
      promote the nuclear expression of GFP and is necessary for the nuclear
      localization of FANCD2. Importantly, mutation of this FANCD2 NLS reveals that
      intact FANCD2 is required for the nuclear localization of a subset of FANCI. In
      addition, the NLS is necessary for the efficient monoubiquitination of FANCD2 and
      FANCI and, consequently, for their localization to chromatin. As a result, FANCD2
      NLS mutants fail to rescue the ICL sensitivity of FA-D2 patient cells. Our
      studies yield important insight into the domain structure of the poorly
      characterized FANCD2 protein, and reveal a previously unknown mechanism for the
      coordinate nuclear import of a subset of FANCD2 and FANCI, a key early step in
      the cellular ICL response. 

PMID- 24278432
TI  - Prenatal glucocorticoid treatment and later mental health in children and
      adolescents.
AB  - BACKGROUND: Animal studies demonstrate a clear link between prenatal exposure to
      glucocorticoids (GC) and altered offspring brain development. We aim to examine
      whether prenatal GC exposure programs long-term mental health in humans. METHODS:
      Using propensity-score-matching, children prenatally exposed to synthetic
      glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important
      confounders related to sGC treatment--gestational age and pre-pregnancy BMI. We
      also used mixed-effects modeling to analyse the entire cohort--matching each sGC
      case, n=37, to all possible controls, n=6079, on gestational age and sex. We
      obtained data from the Northern Finland Birth Cohort 1986 at four waves-
      pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from
      medical records. Mental health was assessed at 8 years by teachers with the
      Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of
      ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self
      Report (YSR) scale. RESULTS: Prenatal sGC treatment was consistently associated
      with adverse mental health in childhood and adolescence, as shown by both the
      propensity-score method and mixed-effects model. Using the propensity-score
      matched subsample, linear multiple regression showed prenatal sGC was
      significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23
      16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for
      relevant confounders. Similar findings were obtained at 16 years, but did not
      reach statistical significance. Mediation by birthweight/placental weight was not
      detected. CONCLUSIONS: This study is the first to prospectively investigate the
      long-term associations between prenatal exposure to sGC treatment and mental
      health in children and adolescents. We report an association between prenatal
      exposure to sGC and child mental health, supportive of the idea that sGC has a
      programming effect on the fetal brain.

PMID- 24278433
TI  - Leishmania amazonensis promastigotes present two distinct modes of nucleus and
      kinetoplast segregation during cell cycle.
AB  - Here, we show the morphological events associated with organelle segregation and
      their timing in the cell cycle of a reference strain of Leishmania (L.)
      amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis
      in the Americas. We show evidences that during the cell cycle, L. amazonensis
      promastigotes present two distinct modes of nucleus and kinetoplast segregation,
      which occur in different temporal order in different proportions of cells. We
      used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing
      organelles and DNA replication in wild-type parasites. The emergence of a new
      flagellum was observed using a specific monoclonal antibody. The results show
      that L. amazonensis cell cycle division is peculiar, with 65% of the dividing
      cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing
      the opposite or duplicating both organelles concomitantly. In both cases, the new
      flagellum appeared during S to G2 phase in 1N1K cells and thus before the
      segregation of both DNA-containing organelles; however, we could not determine
      the exact timing of flagellar synthesis. Most of these results were confirmed by
      the synchronization of parasites using hydroxyurea. Altogether, our data show
      that during the cell cycle of L. amazonensis promastigotes, similarly to L.
      donovani, the segregation of nucleus and kinetoplast do not follow a specific
      order, especially when compared to other trypanosomatids, reinforcing the idea
      that this characteristic seems to be species-specific and may represent
      differences in cellular biology among members of the Leishmania genus. 

PMID- 24278434
TI  - NT-proBNP best predictor of cardiovascular events and cardiovascular mortality in
      secondary prevention in very old age: the Leiden 85-plus Study.
AB  - BACKGROUND: In the aging population cardiovascular disease (CVD) is highly
      prevalent. Identification of very old persons at high risk of recurrent CVD is
      difficult, since traditional risk markers loose predictive value with age.
      METHODS: In a population-based sample of 282 85-year old participants with
      established CVD from the Leiden 85-plus Study, we studied predictive values of
      traditional cardiovascular risk markers, a history of major CVD (myocardial
      infarction, stroke or arterial surgery), and new cardiovascular biomarkers
      (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP),
      homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding
      5-year risk of recurrent cardiovascular events and mortality (composite
      endpoint). RESULTS: During complete 5-year follow-up 157 (56%) participants died.
      109 (39%) had a cardiovascular event or died from cardiovascular causes.
      Individually related to the composite endpoint were: a history of major CVD (HR
      1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI
      1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including
      all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of
      all five new markers only addition of NT-proBNP improved the C-statistic (0.67
      (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement
      for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and
      for homocysteine 24.7% (p=0.04). CONCLUSIONS: Among very old subjects with
      established CVD, NT-proBNP was the strongest risk marker for cardiovascular
      events and cardiovascular mortality. When estimating risk in secondary prevention
      in very old age, use of NT-proBNP should be considered.

PMID- 24278435
TI  - High-frequency stimulation of excitable cells and networks.
AB  - High-frequency (HF) stimulation has been shown to block conduction in excitable
      cells including neurons and cardiac myocytes. However, the precise mechanisms
      underlying conduction block are unclear. Using a multi-scale method, the
      influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo
      and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation
      alters the amplitude and frequency of repetitive firing in response to a constant
      applied current and increases the threshold to evoke a single action potential in
      response to a brief applied current pulse. Further, the excitable cells cannot
      evoke a single action potential or fire repetitively above critical values for
      the HF stimulation amplitude. Analytical expressions for the critical values and
      thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley
      model, it is shown that HF stimulation alters the dynamics of ionic current
      gating, shifting the steady-state activation, inactivation, and time constant
      curves, suggesting several possible mechanisms for conduction block. Finally, we
      demonstrate that HF stimulation of a network of neurons reduces the electrical
      activity firing rate, increases network synchronization, and for a sufficiently
      large HF stimulation, leads to complete electrical quiescence. In this study, we
      demonstrate a novel approach to investigate HF stimulation in biophysically
      detailed ionic models of excitable cells, demonstrate possible mechanisms for HF
      stimulation conduction block in neurons, and provide insight into the influence
      of HF stimulation on neural networks. 

PMID- 24278436
TI  - Elevated procoagulant endothelial and tissue factor expressing microparticles in
      women with recurrent pregnancy loss.
AB  - BACKGROUND: 15% of reproducing couples suffer from pregnancy loss(PL) and recurs
      in 2-3%. One of the most frequently hypothesized causes of unexplained PL refers
      to a defective maternal haemostatic response leading to uteroplacental
      thrombosis. Hereditary thrombophilia and antiphospholipid antibodies have been
      extensively described as risk factors for PL in women with unknown aetiology.
      Recently, a new marker has emerged: the cell-derived procoagulant circulating
      microparticles(MPs) which have been reported to have a major role in many
      thrombosis complicated diseases. This study aims to analyze the significance of
      procoagulant MPs in women suffering from unexplained recurrent pregnancy
      loss(RPL), and characterize their cellular origin. METHOD AND FINDINGS: 115 women
      with RPL were analyzed for common thrombophilia markers and different cell
      derived MPs-total annexinV, platelet(CD41a), endothelial(CD146,CD62e),
      leukocyte(CD45), erythrocyte(CD235a) and tissue factor(CD142)(TF) expressing MPs
      and were compared with 20 healthy non-pregnant women. Methodology for MP analysis
      was standardized by participating in the "Vascular Biology Scientific and
      Standardization Committee workshop". RESULTS: Total annexinV, TF and endothelial
      MPs were found significantly increased(p<0.05, 95% confidence interval) in women
      with RPL. The procoagulant activity of MPs measured by STA-PPL clotting time
      assay was found in correspondence with annexinV MP levels, wherein the clot time
      was shortened in samples with increased MP levels. Differences in platelet,
      leukocyte and erythrocyte derived MPs were not significant. Thirty seven of 115
      women were found to carry any of the acquired or hereditary thrombophilia
      markers. No significant differences were seen in the MP profile of women with and
      without thrombophilia marker. CONCLUSION: The presence of elevated endothelial,
      TF and phosphatidylserine expressing MPs at a distance (at least 3 months) from
      the PL suggests a continued chronic endothelial damage/activation which may get
      exaggerated at the onset of pregnancy. The data suggests that MPs may contribute
      to uteroplacental thrombosis and are associated with the pathogenesis of RPL.

PMID- 24278437
TI  - Prevalence, diversity, and load of Borrelia species in ticks that have fed on
      humans in regions of Sweden and Aland Islands, Finland with different Lyme
      borreliosis incidences.
AB  - The incidence of Lyme borreliosis (LB) in a region may reflect the prevalence of
      Borrelia in the tick population. Our aim was to investigate if regions with
      different LB incidences can be distinguished by studying the prevalence and
      diversity of Borrelia species in their respective tick populations. The Borrelia
      load in a feeding tick increases with the duration of feeding, which may
      facilitate a transmission of Borrelia Spirochetes from tick to host. Therefore,
      we also wanted to investigate how the Borrelia load in ticks that have fed on
      humans varies with the duration of tick feeding. During 2008 and 2009, ticks that
      had bitten humans were collected from four regions of Sweden and Finland, regions
      with expected differences in LB incidence. The duration of tick feeding was
      estimated and Borrelia were detected and quantified by a quantitative PCR assay
      followed by species determination. Out of the 2,154 Ixodes ricinus ticks
      analyzed, 26% were infected with Borrelia and seven species were identified. B.
      spielmanii was detected for the first time in the regions. The tick populations
      collected from the four regions exhibited only minor differences in both
      prevalence and diversity of Borrelia species, indicating that these variables
      alone cannot explain the regions' different LB incidences. The number of Borrelia
      cells in the infected ticks ranged from fewer than ten to more than a million. We
      also found a lower number of Borrelia cells in adult female ticks that had fed
      for more than 36 hours, compared to the number of Borrelia cells found in adult
      female ticks that had fed for less than 36 hours. 

PMID- 24278438
TI  - Improving quality of preventive care at a student-run free clinic.
AB  - Student-run clinics increasingly serve as primary care providers for patients of
      lower socioeconomic status, but studies show that quality of care at student-run
      clinics has room for improvement. PURPOSE: To examine change in provision of
      preventive services in a student-run free clinic after implementation of a
      student-led QI intervention involving prompting. METHOD: Review of patient charts
      pre- and post-intervention, examining adherence to screening guidelines for
      diabetes, dyslipidemia, HIV, and cervical cancer. RESULTS: Adherence to
      guidelines among eligible patients increased after intervention in 3 of 4
      services examined. Receipt of HIV testing increased from 33% (80/240) to 48%
      (74/154; p = 0.004), fasting lipid panel increased from 53% (46/86) to 72%
      (38/53; p = 0.033), and fasting blood glucose increased from 59% (27/46) to 82%
      (18/22; p = 0.059). CONCLUSIONS: This student-run free clinic implemented a
      student-led QI intervention that increased provision of prevention. Such a model
      for QI could extend to other student-run clinics nationally.

PMID- 24278439
TI  - Interpreting quantifier scope ambiguity: evidence of heuristic first, algorithmic
      second processing.
AB  - The present work suggests that sentence processing requires both heuristic and
      algorithmic processing streams, where the heuristic processing strategy precedes
      the algorithmic phase. This conclusion is based on three self-paced reading
      experiments in which the processing of two-sentence discourses was investigated,
      where context sentences exhibited quantifier scope ambiguity. Experiment 1
      demonstrates that such sentences are processed in a shallow manner. Experiment 2
      uses the same stimuli as Experiment 1 but adds questions to ensure deeper
      processing. Results indicate that reading times are consistent with a lexical
      pragmatic interpretation of number associated with context sentences, but
      responses to questions are consistent with the algorithmic computation of
      quantifier scope. Experiment 3 shows the same pattern of results as Experiment 2,
      despite using stimuli with different lexical-pragmatic biases. These effects
      suggest that language processing can be superficial, and that deeper processing,
      which is sensitive to structure, only occurs if required. Implications for recent
      studies of quantifier scope ambiguity are discussed. 

PMID- 24278440
TI  - A novel AtKEA gene family, homolog of bacterial K+/H+ antiporters, plays
      potential roles in K+ homeostasis and osmotic adjustment in Arabidopsis.
AB  - AtKEAs, homologs of bacterial KefB/KefC, are predicted to encode K(+)/H(+)
      antiporters in Arabidopsis. The AtKEA family contains six genes forming two
      subgroups in the cladogram: AtKEA1-3 and AtKEA4-6. AtKEA1 and AtKEA2 have a long
      N-terminal domain; the full-length AtKEA1 was inactive in yeast. The transport
      activity was analyzed by expressing the AtKEA genes in yeast mutants lacking
      multiple ion carriers. AtKEAs conferred resistance to high K(+) and hygromycin B
      but not to salt and Li(+) stress. AtKEAs expressed in both the shoot and root of
      Arabidopsis. The expression of AtKEA1, -3 and -4 was enhanced under low K(+)
      stress, whereas AtKEA2 and AtKEA5 were induced by sorbitol and ABA treatments.
      However, osmotic induction of AtKEA2 and AtKEA5 was not observed in aba2-3
      mutants, suggesting an ABA regulated mechanism for their osmotic response.
      AtKEAs' expression may not be regulated by the SOS pathway since their expression
      was not affected in sos mutants. The GFP tagging analysis showed that AtKEAs
      distributed diversely in yeast. The Golgi localization of AtKEA3 was demonstrated
      by both the stably transformed seedlings and the transient expression in
      protoplasts. Overall, AtKEAs expressed and localized diversely, and may play
      roles in K(+) homeostasis and osmotic adjustment in Arabidopsis. 

PMID- 24278441
TI  - A combinatorial relative mass value evaluation of endogenous bioactive proteins
      in three-dimensional cultured nucleus pulposus cells of herniated intervertebral
      discs: identification of potential target proteins for gene therapeutic
      approaches.
AB  - Painful degenerative disc diseases have been targeted by different biological
      treatment approaches. Nucleus pulposus (NP) cells play a central role in
      intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic and
      inflammatory factors that affect the extracellular matrix. IVD degeneration is
      associated with imbalances of these factors, resulting in a catabolic
      inflammatory metabolism. Therefore, accurate knowledge about their quantity and
      quality with regard to matrix synthesis is vital for a rational gene therapeutic
      approach. NP cells were isolated from 63 patients operated due to lumbar disc
      herniation (mean age 56 / range 29 - 84 years). Then, three-dimensional culture
      with low-glucose was completed in a collagen type I scaffold for four weeks.
      Subsequently cell proliferation evaluation was performed using 3-(4, 5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular
      concentration of 28 endogenously expressed anabolic, catabolic, inflammatory
      factors and relevant matrix proteins was determined by enzyme-linked
      immunosorbent assay. Specimen-related grades of degeneration were confirmed by
      preoperative magnetic resonance imaging. Independent from gender, age and grade
      of degeneration proliferation rates remained similar in all groups of NP cells.
      Progressive grades of degeneration, however, showed a significant influence on
      accumulation of selective groups of factors such as disintegrin and
      metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3,
      metalloproteinase inhibitor 1 and 2, interleukin-1beta and interleukin-1
      receptor. Along with these changes, the key NP matrix proteins aggrecan and
      collagen II decreased significantly. The concentration of anabolic factors bone
      morphogenetic proteins 2, 4, 6 and 7, insulin-like growth factor 1, transforming
      growth factor beta 1 and 3, however, remained below the minimal detectable
      quantities. These findings indicate that progressive degenerative changes in NP
      may be problematic with regard to biologic treatment strategies. Hence, gene
      therapeutic interventions regulating relevant bioactive factors identified in
      this work might contribute to the development of regenerative treatment
      approaches for degenerative disc diseases. 

PMID- 24278442
TI  - Quantitative identification of mutant alleles derived from lung cancer in plasma
      cell-free DNA via anomaly detection using deep sequencing data.
AB  - The detection of rare mutants using next generation sequencing has considerable
      potential for diagnostic applications. Detecting circulating tumor DNA is the
      foremost application of this approach. The major obstacle to its use is the high
      read error rate of next-generation sequencers. Rather than increasing the
      accuracy of final sequences, we detected rare mutations using a semiconductor
      sequencer and a set of anomaly detection criteria based on a statistical model of
      the read error rate at each error position. Statistical models were deduced from
      sequence data from normal samples. We detected epidermal growth factor receptor
      (EGFR) mutations in the plasma DNA of lung cancer patients. Single-pass deep
      sequencing (>100,000 reads) was able to detect one activating mutant allele in
      10,000 normal alleles. We confirmed the method using 22 prospective and 155
      retrospective samples, mostly consisting of DNA purified from plasma. A temporal
      analysis suggested potential applications for disease management and for
      therapeutic decision making to select epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKI). 

PMID- 24278443
TI  - Genetic variability and evolutionary implications of RNA silencing suppressor
      genes in RNA1 of sweet potato chlorotic stunt virus isolates infecting
      sweetpotato and related wild species.
AB  - BACKGROUND: The bipartite single-stranded RNA genome of Sweet potato chlorotic
      stunt virus (SPCSV, genus Crinivirus; Closteroviridae) encodes a Class 1 RNase
      III (RNase3), a putative hydrophobic protein (p7) and a 22-kDa protein (p22) from
      genes located in RNA1. RNase3 and p22 suppress RNA silencing, the basal antiviral
      defence mechanism in plants. RNase3 is sufficient to render sweetpotato (Ipomoea
      batatas) virus-susceptible and predisposes it to development of severe diseases
      following infection with unrelated virus. The incidence, strains and gene content
      of SPCSV infecting wild plant species have not been studied.
      METHODOLOGY/PRINCIPAL FINDINGS: Thirty SPCSV isolates were characterized from 10
      wild Ipomoea species, Hewittia sublobata or Lepistemon owariensis (family
      Convolvulaceae) in Uganda and compared with 34 local SPCSV isolates infecting
      sweetpotatoes. All isolates belonged to the East African (EA) strain of SPCSV and
      contained RNase3 and p7, but p22 was not detected in six isolates. The three
      genes showed only limited genetic variability and the proteins were under
      purifying selection. SPCSV isolates lacking p22 synergized with Sweet potato
      feathery mottle virus (SPFMV, genus potyvirus; Potyviridae) and caused severe
      symptoms in co-infected sweetpotato plants. One SPCSV isolate enhanced
      accumulation of SPFMV, but no severe symptoms developed. A new whitefly
      transmitted virus (KML33b) encoding an RNase3 homolog (<56% identity to SPCSV
      RNase3) able to suppresses sense-mediated RNA silencing was detected in I.
      sinensis. CONCLUSIONS/SIGNIFICANCE: SPCSV isolates infecting wild species and
      sweetpotato in Uganda were genetically undifferentiated, suggesting inter-species
      transmission of SPCSV. Most isolates in Uganda contained p22, unlike SPCSV
      isolates characterized from other countries and continents. Enhanced accumulation
      of SPFMV and increased disease severity were found to be uncoupled phenotypic
      outcomes of RNase3-mediated viral synergism in sweetpotato. A second virus
      encoding an RNase3-like RNA silencing suppressor was detected. Overall, results
      provided many novel and important insights into evolutionary biology of SPCSV.

PMID- 24278444
TI  - Development of a site-directed integration plasmid for heterologous gene
      expression in Mycoplasma gallisepticum.
AB  - Deciphering the molecular basis of the interactions between the parasite
      Mycoplasma gallisepticum and its avian hosts suffers from the lack of genetic
      tools available for the pathogen. In the absence of well established methods for
      targeted disruption of relevant M. gallisepticum genes, we started to develop
      suicide vectors and equipped them with a short fragment of M. gallisepticum
      origin or replication (oriC MG). We failed to create a disruption vector,
      although by adding a further short fragment of the M. gallisepticum tufB upstream
      region we created a "Trojan horse" plasmid. This is fully integrated into the
      genomic DNA of M. gallisepticum, always at the same site, oriC MG, and is able to
      carry and express any gene of interest in the genetic background of M.
      gallisepticum. Successful expression of a heterologous gene was shown with the
      lacZ gene of E. coli. When used for gene complementation or expression of hybrid
      genes in M. gallisepticum, a site-specific combined integration/expression vector
      constitutes an improvement on randomly integrating transposons, which might have
      unexpected effects on the expression of chromosomal genes.

PMID- 24278445
TI  - Repetitive transcranial magnetic stimulation applications normalized prefrontal
      dysfunctions and cognitive-related metabolic profiling in aged mice.
AB  - Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a
      noninvasive brain stimulation technique that has recently received increasing
      interests as a therapeutic procedure for neurodegenerative diseases. To identify
      the metabolism mechanism underlying the improving effects of rTMS, we observed
      that high frequency (25Hz) rTMS for 14 days could reverse the decline of the
      performance of the passive avoidance task in aged mice. We further investigated
      the metabolite profiles in the prefrontal cortex (PFC) in those mice and found
      that rTMS could also reverse the metabolic abnormalities of gamma-aminobutyric
      acid, N-acetyl aspartic, and cholesterol levels to the degree similar to the
      young mice. These data suggested that the rTMS could ameliorate the age-related
      cognitive impairment and improving the metabolic profiles in PFC, and potentially
      can be used to improve cognitive decline in the elderly. 

PMID- 24278446
TI  - The P2Y6 receptor mediates Clostridium difficile toxin-induced CXCL8/IL-8
      production and intestinal epithelial barrier dysfunction.
AB  - C. difficile is a Gram-positive spore-forming anaerobic bacterium that is the
      leading cause of nosocomial diarrhea in the developed world. The pathogenesis of
      C. difficile infections (CDI) is driven by toxin A (TcdA) and toxin B (TcdB),
      secreted factors that trigger the release of inflammatory mediators and
      contribute to disruption of the intestinal epithelial barrier. Neutrophils play a
      key role in the inflammatory response and the induction of pseudomembranous
      colitis in CDI. TcdA and TcdB alter cytoskeletal signaling and trigger the
      release of CXCL8/IL-8, a potent neutrophil chemoattractant, from intestinal
      epithelial cells; however, little is known about the surface receptor(s) that
      mediate these events. In the current study, we sought to assess whether toxin
      induced CXCL8/IL-8 release and barrier dysfunction are driven by the activation
      of the P2Y6 receptor following the release of UDP, a danger signal, from
      intoxicated Caco-2 cells. Caco-2 cells express a functional P2Y6 receptor and
      release measurable amounts of UDP upon exposure to TcdA/B. Toxin-induced CXCL8/IL
      8 production and release were attenuated in the presence of a selective P2Y6
      inhibitor (MRS2578). This was associated with inhibition of TcdA/B-induced
      activation of NFkappaB. Blockade of the P2Y6 receptor also attenuated toxin
      induced barrier dysfunction in polarized Caco-2 cells. Lastly, pretreating mice
      with the P2Y6 receptor antagonists (MSR2578) attenuated TcdA/B-induced
      inflammation and intestinal permeability in an intrarectal toxin exposure model.
      Taken together these data outline a novel role for the P2Y6 receptor in the
      induction of CXCL8/IL-8 production and barrier dysfunction in response to C.
      difficile toxin exposure and may provide a new therapeutic target for the
      treatment of CDI. 

PMID- 24278447
TI  - Working memory in the processing of the Iowa Gambling Task: an individual
      differences approach.
AB  - The Iowa Gambling Task (IGT) is a sequential learning task in which participants
      develop a tendency towards advantageous options arising from the outcomes
      associated with their previous decisions. The role of working memory in this
      complex task has been largely debated in the literature. On one hand, low working
      memory resources lead to a decrease in the number of advantageous decisions and
      make a significant part of participants unable to report explicitly which options
      are the most profitable. On the other hand, several studies have shown no
      contribution of working memory to the IGT decision patterns. In order to
      investigate this apparent incompatibility of results, we used an individual
      differences approach, which has proven an effective method to investigate the
      role of working memory in cognition. We compared the IGT decision patterns of
      participants as a function of their working memory capacity (WMC). As expected,
      contrary to low WMC participants, high WMC participants developed a tendency
      towards advantageous decisions. These findings lead us to discuss the role of WMC
      in decision making tasks. 

PMID- 24278448
TI  - Pyruvate administration reduces recurrent/moderate hypoglycemia-induced cortical
      neuron death in diabetic rats.
AB  - Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes patients.
      Moderate hypoglycemia is not life-threatening, but if experienced recurrently it
      may present several clinical complications. Activated PARP-1 consumes cytosolic
      NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1
      activation may render cells unable to use glucose even when glucose availability
      is restored. Pyruvate, however, can be metabolized in the absence of cytosolic
      NAD. We therefore hypothesized that pyruvate may be able to improve the outcome
      in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating
      hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose
      alone. In an effort to mimic juvenile type 1 diabetes the experiments were
      conducted in one-month-old young rats that were rendered diabetic by
      streptozotocin (STZ, 50mg/kg, i.p.) injection. One week after STZ injection, rats
      were subjected to moderate hypoglycemia by insulin injection (10 U/kg, i.p.)
      without anesthesia for five consecutive days. Pyruvate (500 mg/kg) was given by
      intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M
      hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia,
      neuronal death, oxidative stress, microglial activation and GSH concentrations in
      the cerebral cortex were analyzed. Sparse neuronal death was observed in the
      cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss
      in the cortex after R/M hypoglycemia were all reduced by pyruvate injection.
      These findings suggest that when delivered alongside glucose, pyruvate may
      significantly improve the outcome after R/M hypoglycemia by circumventing a
      sustained impairment in neuronal glucose utilization resulting from PARP-1
      activation.

PMID- 24278449
TI  - Quantification of Hantaan virus with a SYBR green I-based one-step qRT-PCR assay.
AB  - Hantaan virus (HTNV) is a major zoonotic pathogen that causes hemorrhagic fever
      with renal syndrome (HFRS) in Asia, especially in China. Shaanxi province, which
      is located in northwest of China, is one of the areas in China most severely
      afflicted with HFRS epidemics annually. This study aims to establish a
      quantitative RT-PCR (qRT-PCR) assay to detect HTNV both in cell culture and
      clinical serum samples. We established a SYBR Green I-based one-step qRT-PCR
      assay that targets the S segment of the HTNV genome for rapid detection and
      quantification. The HTNV cRNA standards were constructed by in vitro
      transcription, and the copy numbers of the HTNV cRNA were quantified. Standard
      curve was generated by determining the mean cycle threshold (Ct) values versus 10
      fold serial dilutions of the HTNV cRNA over a range of 1 * 10(8) to 1 * 10(3)
      copies/MUl. The standard curve had a reaction efficiency of 102.1%, a correlation
      coefficient (R(2)) of 0.998, and a slope of -3.273. The coefficient of variation
      (CV) of the intra- and inter-assays ranged from 0.68% to 3.00% and from 0.86% to
      3.21%, respectively. The cycle intervals of the qRT-PCR assay between each
      dilution ranged from 2.9 to 3.8 cycles, and the lowest detection limit of the qRT
      PCR assay was 10 copies/MUl. The assay exhibited high specificity that was
      confirmed by melting curve analysis, and no cross reaction with the Seoul virus
      (SEOV) and other viruses (HBV, HCV and HIV) was observed. HTNV RNA was also
      detected in the 27 serum samples of clinical HFRS patients using the assay, and
      the HTNV RNA viral load ranged from 2.06 * 10(1) to 1.95 * 10(5) copies/MUl. The
      SYBR Green I-based one-step qRT-PCR assay is a sensitive, specific, reproducible,
      and simple method for detecting and quantifying HTNV in cell culture and clinical
      samples.

PMID- 24278450
TI  - Gram-positive bacterial lipoglycans based on a glycosylated diacylglycerol lipid
      anchor are microbe-associated molecular patterns recognized by TLR2.
AB  - Innate immune recognition is the first line of host defense against invading
      microorganisms. It is a based on the detection, by pattern recognition receptors
      (PRRs), of invariant molecular signatures that are unique to microorganisms. TLR2
      is a PRR that plays a major role in the detection of Gram-positive bacteria by
      recognizing cell envelope lipid-linked polymers, also called macroamphiphiles,
      such as lipoproteins, lipoteichoic acids and mycobacterial lipoglycans. These
      microbe-associated molecular patterns (MAMPs) display a structure based on a
      lipid anchor, being either an acylated cysteine, a glycosylated diacylglycerol or
      a mannosyl-phosphatidylinositol respectively, and having in common a
      diacylglyceryl moiety. A fourth class of macroamphiphile, namely lipoglycans,
      whose lipid anchor is made, as for lipoteichoic acids, of a glycosylated
      diacylglycerol unit rather than a mannosyl-phosphatidylinositol, is found in Gram
      positive bacteria and produced by certain Actinobacteria, including Micrococcus
      luteus, Stomatococcus mucilaginosus and Corynebacterium glutamicum. We report
      here that these alternative lipoglycans are also recognized by TLR2 and that they
      stimulate TLR2-dependant cytokine production, including IL-8, TNF-alpha and IL-6,
      and cell surface co-stimulatory molecule CD40 expression by a human macrophage
      cell line. However, they differ by their co-receptor requirement and the
      magnitude of the innate immune response they elicit. M. luteus and S.
      mucilaginosus lipoglycans require TLR1 for recognition by TLR2 and induce
      stronger responses than C. glutamicum lipoglycan, sensing of which by TLR2 is
      dependent on TLR6. These results expand the repertoire of MAMPs recognized by
      TLR2 to lipoglycans based on a glycosylated diacylglycerol lipid anchor and
      reinforce the paradigm that macroamphiphiles based on such an anchor, including
      lipoteichoic acids and alternative lipoglycans, induce TLR2-dependant innate
      immune responses. 

PMID- 24278451
TI  - The effect of CO2 on algal growth in industrial waste water for bioenergy and
      bioremediation applications.
AB  - The energy, mining and mineral processing industries are point sources of metal
      contaminated waste water and carbon dioxide (CO2). Freshwater macroalgae from the
      genus Oedogonium can be grown in metal-contaminated waste water to generate
      biomass for bioenergy applications and concomitantly bioremediate metals.
      However, interactions between CO2 addition and algal growth, which can affect
      bioremediation, remain untested. The addition of CO2 to algal cultures in the Ash
      Dam Water (ADW) from a coal-fired power station increased the biomass
      productivity of Oedogonium sp. from 6.8 g dry weight (DW) m(-2) d(-1) to a
      maximum of 22.5 g DW m(-2) d(-1). The greater productivity increased the rate of
      bioremediation of most elements. However, over time carbon-amended cultures
      experienced a decline in productivity. Possible explanations include metal
      toxicity at low pH or essential trace element limitation as a result of
      competition between toxic and essential trace elements for uptake into algae.
      Higher productivity increased bioremediation rate and yielded more biomass for
      bioenergy applications, making maintenance of maximum productivity the central
      aim of the integrated culture model. To do so it will be necessary to resolve the
      mechanisms responsible for declining yields over time in carbon-amended cultures.
      Regardless, our data demonstrate that freshwater macroalgae are ideal candidates
      for bioremediation of metal-contaminated waste streams. Algal culture delivered
      significant improvement in ADW quality, reducing 5 elements that were initially
      in excess of water quality criteria (Al, As, Cd, Ni and Zn) to meet guidelines
      within two to four weeks. 

PMID- 24278452
TI  - Effects of Syzygium aromaticum-derived triterpenes on postprandial blood glucose
      in streptozotocin-induced diabetic rats following carbohydrate challenge.
AB  - PURPOSE: Recent reports suggest that the hypoglycaemic effects of the triterpenes
      involve inhibition of glucose transport in the small intestine. Therefore, the
      effects of Syzygium spp-derived triterpenes oleanolic acid (OA) and maslinic acid
      (MA) were evaluated on carbohydrate hydrolyzing enzymes in STZ-induced diabetic
      rats and consequences on postprandial hyperglycaemia after carbohydrate loading.
      METHODS: We determined using Western blot analysis the expressions of alpha
      amylase and alpha-glucosidase and glucose transporters SGLT1 and GLUT2 in the
      small intestine intestines isolated from diabetic rats treated with OA/MA for 5
      weeks. In vitro assays were used to assess the inhibitory activities of OA and MA
      against alpha-amylase, alpha-glucosidase and sucrase. RESULTS: OA and MA
      ameliorated postprandial hyperglycemia in carbohydrate loaded diabetic rats as
      indicated by the significantly small glucose area under the curve (AUC) in
      treated diabetic animals compared with that in untreated diabetic rats. Western
      blotting showed that OA and MA treatment not only down-regulated the increase of
      SGLT1 and GLUT2 expressions in the small intestine of STZ-induced diabetic rats,
      but also inhibited small intestine alpha-amylase, sucrase and alpha-glucosidase
      activity. IC50 values of OA against alpha-amylase (3.60 +/- 0.18 mmol/L), alpha
      glucosidase (12.40 +/- 0.11 mmol/L) and sucrase (11.50 +/- 0.13 mmol/L) did not
      significantly differ from those of OA and acarbose. CONCLUSIONS: The results of
      suggest that OA and MA may be used as potential supplements for treating
      postprandial hyperglycemia. NOVELTY OF THE WORK: The present observations
      indicate that besides improving glucose homeostasis in diabetes, OA and MA
      suppress postprandial hyperglycaemia mediated in part via inhibition of
      carbohydrate hydrolysis and reduction of glucose transporters in the
      gastrointestinal tract. Inhibition of alpha-glucosidase and alpha-amylase can
      significantly decrease the postprandial hyperglycaemia after a mixed carbohydrate
      diet and therefore can be an important strategy in the management of postprandial
      blood glucose levels in NIDDM patients.

PMID- 24278453
TI  - Complete atrial-specific knockout of sodium-calcium exchange eliminates
      sinoatrial node pacemaker activity.
AB  - The origin of sinoatrial node (SAN) pacemaker activity in the heart is
      controversial. The leading candidates are diastolic depolarization by "funny"
      current (If) through HCN4 channels (the "Membrane Clock" hypothesis),
      depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca
      cycling (the "Calcium Clock" hypothesis), and a combination of the two ("Coupled
      Clock"). To address this controversy, we used Cre/loxP technology to generate
      atrial-specific NCX1 KO mice. NCX1 protein was undetectable in KO atrial tissue,
      including the SAN. Surface ECG and intracardiac electrograms showed no atrial
      depolarization and a slow junctional escape rhythm in KO that responded
      appropriately to beta-adrenergic and muscarinic stimulation. Although KO atria
      were quiescent they could be stimulated by external pacing suggesting that
      electrical coupling between cells remained intact. Despite normal
      electrophysiological properties of If in isolated patch clamped KO SAN cells,
      pacemaker activity was absent. Recurring Ca sparks were present in all KO SAN
      cells, suggesting that Ca cycling persists but is uncoupled from the sarcolemma.
      We conclude that NCX1 is required for normal pacemaker activity in murine SAN. 

PMID- 24278454
TI  - A novel in vitro model to study pericytes in the neurovascular unit of the
      developing cortex.
AB  - Cortical function is impaired in various disorders of the central nervous system
      including Alzheimer's disease, autism and schizophrenia. Some of these disorders
      are speculated to be associated with insults in early brain development.
      Pericytes have been shown to regulate neurovascular integrity in development,
      health and disease. Hence, precisely controlled mechanisms must have evolved in
      evolution to operate pericyte proliferation, repair and cell fate within the
      neurovascular unit (NVU). It is well established that pericyte deficiency leads
      to NVU injury resulting in cognitive decline and neuroinflammation in cortical
      layers. However, little is known about the role of pericytes in
      pathophysiological processes of the developing cortex. Here we introduce an in
      vitro model that enables to precisely study pericytes in the immature cortex and
      show that moderate inflammation and hypoxia result in caspase-3 mediated pericyte
      loss. Using heterozygous EYFP-NG2 mouse mutants we performed live imaging of
      pericytes for several days in vitro. In addition we show that pericytes maintain
      their capacity to proliferate which may allow cell-based therapies like
      reprogramming of pericytes into induced neuronal cells in the presented approach.

PMID- 24278455
TI  - Improved coomassie blue dye-based fast staining protocol for proteins separated
      by SDS-PAGE.
AB  - The time required to visualize proteins using Coomassie Blue dye has been
      significantly reduced with the introduction of fast staining protocols based on
      staining with a Coomassie Blue dye solution at boiling temperatures. However,
      fast stainings suffer from high gel backgrounds, reducing the signal-to-noise
      ratio and limiting the number of detectable spots in the case of 2D SDS-PAGE. The
      aim of this work was to eliminate the high gel background, and thus improve fast
      staining protocols based on Coomassie Blue dye. We show that merely replacing
      water with a 4 mM EDTA washing solution at boiling temperatures, results in a
      transparent gel background within 50 to 60 minutes of destaining. Moreover, when
      a combination of imidazole-zinc reverse staining and Coomassie Blue-based fast
      staining is used the sensitivity is improved significantly; nanogram amounts of
      proteins can be detected using 1D SDS-PAGE, and about 30% to 60% more spots can
      be detected with 2D SDS-PAGE in plasma, platelet, and rat brain tissue samples.
      This work represents an optimized fast staining protocol with improved
      sensitivity, requiring between 60 to 75 minutes to complete protein
      visualization. 

PMID- 24278456
TI  - Emotion through locomotion: gender impact.
AB  - Body language reading is of significance for daily life social cognition and
      successful social interaction, and constitutes a core component of social
      competence. Yet it is unclear whether our ability for body language reading is
      gender specific. In the present work, female and male observers had to visually
      recognize emotions through point-light human locomotion performed by female and
      male actors with different emotional expressions. For subtle emotional
      expressions only, males surpass females in recognition accuracy and readiness to
      respond to happy walking portrayed by female actors, whereas females exhibit a
      tendency to be better in recognition of hostile angry locomotion expressed by
      male actors. In contrast to widespread beliefs about female superiority in social
      cognition, the findings suggest that gender effects in recognition of emotions
      from human locomotion are modulated by emotional content of actions and opposite
      actor gender. In a nutshell, the study makes a further step in elucidation of
      gender impact on body language reading and on neurodevelopmental and psychiatric
      deficits in visual social cognition. 

PMID- 24278457
TI  - Reduced levels of NR1 and NR2A with depression-like behavior in different brain
      regions in prenatally stressed juvenile offspring.
AB  - Adolescence is a time of continued brain maturation, particularly in limbic and
      cortical regions, which undoubtedly plays a role in the physiological and
      emotional changes. Juvenile rats repeatedly exposed to prenatal stress (PS)
      exhibit behavioral features often observed in neuropsychiatric disorders
      including depression. However, to date the underlying neurological mechanisms are
      still unclear. In the current study, juvenile offspring rats whose mothers were
      exposed to PS were evaluated for depression-related behaviors in open field and
      sucrose preference test. NMDA receptor subunits NR1 and NR2A in the hippocampus,
      frontal cortex and striatum were assayed by western blotting. The results
      indicated that PS resulted in several behavioral anomalies in the OFT and sucrose
      preference test. Moreover, reduced levels of NMDA receptor subunits NR1 and NR2A
      in the hippocampus, and NR1 in prefrontal cortex and striatum of prenatally
      stressed juvenile offspring were found. Treatment with MK-801 to pregnant dams
      could prevent all those changes in the juvenile offspring. Collectivity, these
      data support the argument that PS to pregnant dams could induce depression-like
      behavior, which may be involved with abnormal expression of NR1 and NR2A in
      specific brain regions, and MK-801 may have antidepressant-like effects on the
      juvenile offspring. 

PMID- 24278458
TI  - Transcription of Ehrlichia chaffeensis genes is accomplished by RNA polymerase
      holoenzyme containing either sigma 32 or sigma 70.
AB  - Bacterial gene transcription is initiated by RNA polymerase containing a sigma
      factor. To understand gene regulation in Ehrlichia chaffeensis, an important tick
      transmitted rickettsiae responsible for human monocytic ehrlichiosis, we
      initiated studies evaluating the transcriptional machinery of several genes of
      this organism. We mapped the transcription start sites of 10 genes and evaluated
      promoters of five genes (groE, dnaK, hup, p28-Omp14 and p28-Omp19 genes). We
      report here that the RNA polymerase binding elements of E. chaffeensis gene
      promoters are highly homologous for its only two transcription regulators, sigma
      32 and sigma 70, and that gene expression is accomplished by either of the
      transcription regulators. RNA analysis revealed that although transcripts for
      both sigma 32 and sigma 70 are upregulated during the early replicative stage,
      their expression patterns remained similar for the entire replication cycle. We
      further present evidence demonstrating that the organism's -35 motifs are
      essential to transcription initiations. The data suggest that E. chaffeensis gene
      regulation has evolved to support the organism's growth, possibly to facilitate
      its intraphagosomal growth. Considering the limited availability of genetic
      tools, this study offers a novel alternative in defining gene regulation in E.
      chaffeensis and other related intracellular pathogens. 

PMID- 24278459
TI  - Critical role of regulator G-protein signaling 10 (RGS10) in modulating
      macrophage M1/M2 activation.
AB  - Regulator of G protein signaling 10 (RGS10), a GTPase accelerating protein (GAP)
      for G alpha subunits, is a negative regulator of NF-kappaB in microglia. Here, we
      investigated the role of RGS10 in macrophages, a closely related myeloid-derived
      cell type. Features of classical versus alternative activation were assessed in
      Rgs10-/- peritoneal and bone marrow-derived macrophages upon LPS or IL-4
      treatments, respectively. Our results showed that Rgs10-/- macrophages produced
      higher levels of pro-inflammatory cytokines including TNF, IL-1beta and IL-12p70
      in response to LPS treatment and exerted higher cytotoxicity on dopaminergic MN9D
      neuroblastoma cells. We also found that Rgs10-/- macrophages displayed a blunted
      M2 phenotype upon IL-4 priming. Specifically, Rgs10-/- macrophages displayed
      lower YM1 and Fizz1 mRNA levels as measured by QPCR compared to wild type
      macrophages upon IL-4 treatment and this response was not attributable to
      differences in IL-4 receptor expression. Importantly, phagocytic activities of
      Rgs10-/- macrophages were blunted in response to IL-4 priming and/or LPS
      treatments. However, there was no difference in chemotaxis between Rgs10-/- and
      WT macrophages. Our data indicate that Rgs10-/- macrophages displayed
      dysregulated M1 responses along with blunted M2 alternative activation responses,
      suggesting that RGS10 plays an important role in determining macrophage
      activation responses. 

PMID- 24278460
TI  - RNA-seq profiles of immune related genes in the staghorn coral Acropora
      cervicornis infected with white band disease.
AB  - Coral diseases are among the most serious threats to coral reefs worldwide, yet
      most coral diseases remain poorly understood. How the coral host responds to
      pathogen infection is an area where very little is known. Here we used next
      generation RNA-sequencing (RNA-seq) to produce a transcriptome-wide profile of
      the immune response of the Staghorn coral Acropora cervicornis to White Band
      Disease (WBD) by comparing infected versus healthy (asymptomatic) coral tissues.
      The transcriptome of A. cervicornis was assembled de novo from A-tail selected
      Illumina mRNA-seq data from whole coral tissues, and parsed bioinformatically
      into coral and non-coral transcripts using existing Acropora genomes in order to
      identify putative coral transcripts. Differentially expressed transcripts were
      identified in the coral and non-coral datasets to identify genes that were up-
      and down-regulated due to disease infection. RNA-seq analyses indicate that
      infected corals exhibited significant changes in gene expression across 4% (1,805
      out of 47,748 transcripts) of the coral transcriptome. The primary response to
      infection included transcripts involved in macrophage-mediated pathogen
      recognition and ROS production, two hallmarks of phagocytosis, as well as key
      mediators of apoptosis and calcium homeostasis. The strong up-regulation of the
      enzyme allene oxide synthase-lipoxygenase suggests a key role of the allene oxide
      pathway in coral immunity. Interestingly, none of the three primary innate immune
      pathways--Toll-like receptors (TLR), Complement, and prophenoloxydase pathways,
      were strongly associated with the response of A. cervicornis to infection. Five
      hundred and fifty differentially expressed non-coral transcripts were classified
      as metazoan (n = 84), algal or plant (n = 52), fungi (n = 24) and protozoans (n =
      13). None of the 52 putative Symbiodinium or algal transcript had any clear
      immune functions indicating that the immune response is driven by the coral host,
      and not its algal symbionts.

PMID- 24278462
TI  - Increased adiposity in adults born preterm and their children.
AB  - BACKGROUND: Preterm birth is associated with abnormalities in growth, body
      composition, and metabolism during childhood, but adult data are scarce and none
      exist for their offspring. We therefore aimed to examine body composition and
      cardiovascular risk factors in adults born preterm and their children. METHODS: A
      cohort of 52 adults (aged 35.7 years, 54% female, 31 born preterm) and their term
      born children (n=61, aged 8.0 years, 54% female, 60% from a preterm parent) were
      studied. Auxology and body composition (whole-body dual-energy X-ray
      absorptiometry) were measured, and fasting blood samples taken for metabolic and
      hormonal assessments. RESULTS: Adults born preterm had greater abdominal
      adiposity, displaying more truncal fat (p=0.006) and higher android to gynoid fat
      ratio (p=0.004). Although women born preterm and at term were of similar weight
      and BMI, men born preterm (n=8) were on average 20 kg heavier (p=0.010) and of
      greater BMI (34.2 vs 28.4 kg/m(2); p=0.021) than men born at term (n=16). Adults
      born preterm also displayed a less favourable lipid profile, including lower HDL
      C concentrations (p=0.007) and greater total cholesterol to HDL-C ratio
      (p=0.047). Children of parents born preterm tended to have more body fat than the
      children of parents born at term (21.3 vs 17.6%; p=0.055). Even after adjustment
      for mean parental BMI, children of parents born preterm had altered fat
      distribution, with more truncal fat (p=0.048) and greater android to gynoid fat
      ratio (p=0.009). CONCLUSIONS: Adults born preterm, particularly men, have
      markedly increased fat mass and altered fat distribution. A similar increase in
      abdominal adiposity was observed in the term born offspring of parents born
      preterm, indicating that adverse outcomes associated with preterm birth may
      extend to the next generation.

PMID- 24278461
TI  - Prdm6 is essential for cardiovascular development in vivo.
AB  - Members of the PRDM protein family have been shown to play important roles during
      embryonic development. Previous in vitro and in situ analyses indicated a
      function of Prdm6 in cells of the vascular system. To reveal physiological
      functions of Prdm6, we generated conditional Prdm6-deficient mice. Complete
      deletion of Prdm6 results in embryonic lethality due to cardiovascular defects
      associated with aberrations in vascular patterning. However, smooth muscle cells
      could be regularly differentiated from Prdm6-deficient embryonic stem cells and
      vascular smooth muscle cells were present and proliferated normally in Prdm6
      deficient embryos. Conditional deletion of Prdm6 in the smooth muscle cell
      lineage using a SM22-Cre driver line resulted in perinatal lethality due to
      hemorrhage in the lungs. We thus identified Prdm6 as a factor that is essential
      for the physiological control of cardiovascular development. 

PMID- 24278463
TI  - Odor detection in Manduca sexta is optimized when odor stimuli are pulsed at a
      frequency matching the wing beat during flight.
AB  - Sensory systems sample the external world actively, within the context of self
      motion induced disturbances. Mammals sample olfactory cues within the context of
      respiratory cycles and have adapted to process olfactory information within the
      time frame of a single sniff cycle. In plume tracking insects, it remains unknown
      whether olfactory processing is adapted to wing beating, which causes similar
      physical effects as sniffing. To explore this we first characterized the physical
      properties of our odor delivery system using hotwire anemometry and photo
      ionization detection, which confirmed that odor stimuli were temporally
      structured. Electroantennograms confirmed that pulse trains were tracked
      physiologically. Next, we quantified odor detection in moths in a series of
      psychophysical experiments to determine whether pulsing odor affected acuity.
      Moths were first conditioned to respond to a target odorant using Pavlovian
      olfactory conditioning. At 24 and 48 h after conditioning, moths were tested with
      a dilution series of the conditioned odor. On separate days odor was presented
      either continuously or as 20 Hz pulse trains to simulate wing beating effects. We
      varied pulse train duty cycle, olfactometer outflow velocity, pulsing method, and
      odor. Results of these studies, established that detection was enhanced when
      odors were pulsed. Higher velocity and briefer pulses also enhanced detection.
      Post hoc analysis indicated enhanced detection was the result of a significantly
      lower behavioral response to blank stimuli when presented as pulse trains. Since
      blank responses are a measure of false positive responses, this suggests that the
      olfactory system makes fewer errors (i.e. is more reliable) when odors are
      experienced as pulse trains. We therefore postulate that the olfactory system of
      Manduca sexta may have evolved mechanisms to enhance odor detection during
      flight, where the effects of wing beating represent the norm. This system may
      even exploit temporal structure in a manner similar to sniffing. 

PMID- 24278464
TI  - Preserved discrimination performance and neural processing during crossmodal
      attention in aging.
AB  - In a recent study in younger adults (19-29 year olds) we showed evidence that
      distributed audiovisual attention resulted in improved discrimination performance
      for audiovisual stimuli compared to focused visual attention. Here, we extend our
      findings to healthy older adults (60-90 year olds), showing that performance
      benefits of distributed audiovisual attention in this population match those of
      younger adults. Specifically, improved performance was revealed in faster
      response times for semantically congruent audiovisual stimuli during distributed
      relative to focused visual attention, without any differences in accuracy. For
      semantically incongruent stimuli, discrimination accuracy was significantly
      improved during distributed relative to focused attention. Furthermore, event
      related neural processing showed intact crossmodal integration in higher
      performing older adults similar to younger adults. Thus, there was insufficient
      evidence to support an age-related deficit in crossmodal attention. 

PMID- 24278465
TI  - SAMSN1 is highly expressed and associated with a poor survival in glioblastoma
      multiforme.
AB  - OBJECTIVES: To study the expression pattern and prognostic significance of SAMSN1
      in glioma. METHODS: Affymetrix and Arrystar gene microarray data in the setting
      of glioma was analyzed to preliminarily study the expression pattern of SAMSN1 in
      glioma tissues, and Hieratical clustering of gene microarray data was performed
      to filter out genes that have prognostic value in malignant glioma. Survival
      analysis by Kaplan-Meier estimates stratified by SAMSN1 expression was then made
      based on the data of more than 500 GBM cases provided by The Cancer Genome Atlas
      (TCGA) project. At last, we detected the expression of SAMSN1 in large numbers of
      glioma and normal brain tissue samples using Tissue Microarray (TMA). Survival
      analysis by Kaplan-Meier estimates in each grade of glioma was stratified by
      SAMSN1 expression. Multivariate survival analysis was made by Cox proportional
      hazards regression models in corresponding groups of glioma. RESULTS: With the
      expression data of SAMSN1 and 68 other genes, high-grade glioma could be
      classified into two groups with clearly different prognoses. Gene and large
      sample tissue microarrays showed high expression of SAMSN1 in glioma particularly
      in GBM. Survival analysis based on the TCGA GBM data matrix and TMA multi-grade
      glioma dataset found that SAMSN1 expression was closely related to the prognosis
      of GBM, either PFS or OS (P<0.05). Multivariate survival analysis with Cox
      proportional hazards regression models confirmed that high expression of SAMSN1
      was a strong risk factor for PFS and OS of GBM patients. CONCLUSION: SAMSN1 is
      over-expressed in glioma as compared with that found in normal brains, especially
      in GBM. High expression of SAMSN1 is a significant risk factor for the
      progression free and overall survival of GBM.

PMID- 24278466
TI  - Gene expression, single nucleotide variant and fusion transcript discovery in
      archival material from breast tumors.
AB  - Advantages of RNA-Seq over array based platforms are quantitative gene expression
      and discovery of expressed single nucleotide variants (eSNVs) and fusion
      transcripts from a single platform, but the sensitivity for each of these
      characteristics is unknown. We measured gene expression in a set of manually
      degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from
      breast tumor with the hybridization based, NanoString nCounter (226 gene panel)
      and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library
      preparation kits. We performed correlation analyses of gene expression between
      samples and across platforms. We then specifically assessed whole transcriptome
      expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE
      RNA-Seq data. For gene expression in the manually degraded samples, we observed
      Pearson correlations of >0.94 and >0.80 with NanoString and ScriptSeq protocols,
      respectively. Gene expression data for matched fresh-frozen and FFPE samples
      yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes)
      and ScriptSeq whole transcriptome protocols respectively, p<2x10(-16).
      Specifically for lincRNAs, we observed superb Pearson correlation (0.988) between
      matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq
      platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we
      detected 53.4% of high confidence SNVs and 24% of high confidence fusion
      transcripts. Sensitivity of fusion transcript detection was not overcome by an
      increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million
      reads). Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene
      expression data for degraded and FFPE material. The high degree of correlation
      between NanoString and RNA-Seq platforms suggests discovery based whole
      transcriptome studies from FFPE material will produce reliable expression data.
      The RiboZeroGold ScriptSeq protocol performed particularly well for lincRNA
      expression from FFPE libraries, but detection of eSNV and fusion transcripts was
      less sensitive. 

PMID- 24278467
TI  - Horizontal body position reduces cortical pain-related processing: evidence from
      late ERPs.
AB  - The present study investigated the influence of short-term horizontal body
      position on pain-related somatosensory processing, by measuring subjective and
      cortical responses to electrical pain stimulation. Twenty-eight healthy women
      were randomly assigned to either the experimental horizontal group (Bed Rest, BR)
      or to the sitting control group (Sitting Control, SC). After 90 minutes in either
      horizontal or sitting position, the individual pain thresholds were assessed and
      EEG/self-evaluations recorded during the administration of 180 stimuli delivered
      to the left forearm. Electrical pain stimuli, calibrated to subjects' individual
      pain thresholds, consisted of two different intensity levels: no pain (40% below
      pain threshold) and pain (40% above pain threshold). Compared with control, BR
      condition significantly inhibited subjective sensitivity to painless stimuli,
      whereas electrophysiological results pointed to a reduced slow cortical wave
      (interval: 300-600 ms) at all stimulus intensities, and smaller amplitude in BR's
      right vs. left prefrontal sites. sLORETA analysis revealed that cortical
      responses were associated with a decreased activation of superior frontal gyrus
      and anterior cingulate cortex (BA 6/24). Interestingly, BR group only showed
      significant negative correlations between self-evaluation of painful intensities
      and frontal cortical negativity, revealing increasingly differentiated responses
      in bed rest: indeed those BR participants who reported lower pain ratings,
      displayed reduced negativity within anterior regions. Taken together, results
      indicate that short-term horizontal position is able to inhibit a fronto-parietal
      pain network, particularly at the level of central prefrontal regions typically
      involved in cognitive, affective and motor aspects of pain processing. 

PMID- 24278468
TI  - A female-emitted pheromone component is associated with reduced male courtship in
      the parasitoid wasp Spalangia endius.
AB  - During courtship interactions, the courted individual may not always be prepared
      to mate. For example, mating or courtship may be detrimental to its fitness and
      resistance is expected under these circumstances. As such, various resistance
      strategies have evolved, from physically fending off courting individuals to
      producing behavioural signals of unreceptivity. In the parasitoid wasp Spalangia
      endius, females rarely re-mate and mated females are avoided by males in favour
      of virgin females. Further, mated females appear to advertise their mating status
      by the release of a pheromone component (methyl 6-methylsalicylate), but direct
      evidence of the nature of this release is lacking. Here we used real-time
      chemical analysis to track the emission of the pheromone component during
      courtship interactions between virgin males and either virgin or mated females.
      We found that females actively release methyl 6-methylsalicylate when courted and
      that significantly greater concentrations are released by previously mated
      females. Further, high concentrations of this component are associated with both
      the prevention and termination of courtship. 

PMID- 24278469
TI  - Biochemistry changes that occur after death: potential markers for determining
      post-mortem interval.
AB  - Death is likely to result in very extensive biochemical changes in all body
      tissues due to lack of circulating oxygen, altered enzymatic reactions, cellular
      degradation, and cessation of anabolic production of metabolites. These
      biochemical changes may provide chemical markers for helping to more accurately
      determine the time since death (post-mortem interval), which is challenging to
      establish with current observation-based methodologies. In this study blood pH
      and changes in concentration of six metabolites (lactic acid, hypoxanthine, uric
      acid, ammonia, NADH and formic acid) were examined post-mortem over a 96 hour
      period in blood taken from animal corpses (rat and pig) and blood from rats and
      humans stored in vitro. The pH and the concentration of all six metabolites
      changed post-mortem but the extent and rate of change varied. Blood pH in corpses
      fell from 7.4 to 5.1. Concentrations of hypoxanthine, ammonia, NADH and formic
      acid all increased with time and these metabolites may be potential markers for
      post-mortem interval. The concentration of lactate increased and then remained at
      an elevated level and changes in the concentration were different in the rat
      compared to the human and pig. This is the first systematic study of multiple
      metabolic changes post-mortem and demonstrates the nature and extent of the
      changes that occur, in addition to identifying potential markers for estimating
      post-mortem interval. 

PMID- 24278470
TI  - Unique responsiveness of angiosperm stomata to elevated CO2 explained by calcium
      signalling.
AB  - Angiosperm and conifer tree species respond differently when exposed to elevated
      CO2, with angiosperms found to dynamically reduce water loss while conifers
      appear insensitive. Such distinct responses are likely to affect competition
      between these tree groups as atmospheric CO2 concentration rises. Seeking the
      mechanism behind this globally important phenomenon we targeted the Ca(2+)
      dependent signalling pathway, a mediator of stomatal closure in response to
      elevated CO2, as a possible explanation for the differentiation of stomatal
      behaviours. Sampling across the diversity of vascular plants including
      lycophytes, ferns, gymnosperms and angiosperms we show that only angiosperms
      possess the stomatal behaviour and prerequisite genetic coding, linked to Ca(2+)
      dependent stomatal signalling. We conclude that the evolution of Ca(2+)-dependent
      stomatal signalling gives angiosperms adaptive benefits in terms of highly
      efficient water use, but that stomatal sensitivity to high CO2 may penalise
      angiosperm productivity relative to other plant groups in the current era of
      soaring atmospheric CO2. 

PMID- 24278471
TI  - Efficacy and safety of using antifibrinolytic agents in spine surgery: a meta
      analysis.
AB  - PURPOSE: Spine surgery, particularly reconstructive surgery, can be associated
      with significant blood loss, and blood transfusion. Antifibrinolytic agents are
      used routinely to reduce bleeding in cardiac, orthopaedic, and hepatic surgery.
      The purpose of this study was to assess the efficacy and safety of using
      antifibrinolytic agents in reducing blood loss and blood transfusions in spine
      surgery. METHODS: A systematic search of all related studies written in English
      published by October 2012 was conducted using the MEDLINE, EMBASE and the
      Cochrane Library databases. Randomized controlled trials that reported the drug
      dosage, total blood loss, blood transfusion and incidence of deep vein thrombosis
      as the primary outcome were included. RESULTS: Nine studies involving 482
      patients were identified. Patients receiving antifibrinolytic agents had reduced
      blood loss (WMD =-288.8, 95 % CI - 46.49, - 110.19; P = 0.002), reduced blood
      transfusion (WMD =-242.7, 95 % CI - 422.57, - 62.95; P = 0.008), reduced blood
      transfusion rate (RR 0.73, 95% CI 0.58, 0.93; p = 0.010) and no increase (RR
      0.25, 95 % CI 0.03, 2.22; P = 0.21) in the risk of deep vein thrombosis.
      CONCLUSIONS: We conclude that antifibrinolytic agents significantly decrease
      blood loss, blood transfusion, and there is no increase in the risk of deep vein
      thrombosisfor transfusion requirements in spine surgery.

PMID- 24278472
TI  - Membrane orientation and binding determinants of G protein-coupled receptor
      kinase 5 as assessed by combined vibrational spectroscopic studies.
AB  - G-protein coupled receptors (GPCRs) are integral membrane proteins involved in a
      wide variety of biological processes in eukaryotic cells, and are targeted by a
      large fraction of marketed drugs. GPCR kinases (GRKs) play important roles in
      feedback regulation of GPCRs, such as of beta-adrenergic receptors in the heart,
      where GRK2 and GRK5 are the major isoforms expressed. Membrane targeting is
      essential for GRK function in cells. Whereas GRK2 is recruited to the membrane by
      heterotrimeric Gbetagamma subunits, the mechanism of membrane binding by GRK5 is
      not fully understood. It has been proposed that GRK5 is constitutively associated
      with membranes through elements located at its N-terminus, its C-terminus, or
      both. The membrane orientation of GRK5 is also a matter of speculation. In this
      work, we combined sum frequency generation (SFG) vibrational spectroscopy and
      attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR)
      to help determine the membrane orientation of GRK5 and a C-terminally truncated
      mutant (GRK51-531) on membrane lipid bilayers. It was found that GRK5 and GRK51
      531 adopt a similar orientation on model cell membranes in the presence of PIP2
      that is similar to that predicted for GRK2 in prior studies. Mutation of the N
      terminal membrane binding site of GRK5 did not eliminate membrane binding, but
      prevented observation of this discrete orientation. The C-terminus of GRK5 does
      not have substantial impact on either membrane binding or orientation in this
      model system. Thus, the C-terminus of GRK5 may drive membrane binding in cells
      via interactions with other proteins at the plasma membrane or bind in an
      unstructured manner to negatively charged membranes. 

PMID- 24278473
TI  - SIRT1 catalytic activity has little effect on tumor formation and metastases in a
      mouse model of breast cancer.
AB  - The protein deacetylase SIRT1 has been implicated in the regulation of a large
      number of cellular processes that are thought to be required for cancer
      initiation and progression. There are conflicting data that make it unclear
      whether Sirt1 functions as an oncogene or tumor suppressor. To assess the effect
      of SIRT1 on the emergence and progression of mammary tumors, we crossed mice that
      harbor a point mutation that abolishes SIRT1 catalytic activity with mice
      carrying the polyoma middle T transgene driven by the murine mammary tumor virus
      promoter (MMTV-PyMT). The absence of SIRT1 catalytic activity neither accelerated
      nor blocked the formation of tumors and metastases in this model. There was a lag
      in tumor latency that modestly extended survival in Sirt1 mutant mice that we
      attribute to a delay in mammary gland development and not to a direct effect of
      SIRT1 on carcinogenesis. These results are consistent with previous evidence
      suggesting that Sirt1 is not a tumor promoter or a tumor suppressor. 

PMID- 24278474
TI  - Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using
      biophotonic imaging.
AB  - Streptococcus pyogenes infection of the nasopharynx represents a key step in the
      pathogenic cycle of this organism and a major focus for vaccine development,
      requiring robust models to facilitate the screening of potentially protective
      antigens. One antigen that may be an important target for vaccination is the
      chemokine protease, SpyCEP, which is cell surface-associated and plays a role in
      pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the
      spatial location and abundance of bioluminescent bacteria in vivo. We have
      developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by
      transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation
      of isogenic recombinant strains in vitro and in vivo confirmed that
      bioluminescence conferred a growth deficit that manifests as a fitness cost
      during infection. Notwithstanding this, bioluminescence expression permitted non
      invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx
      albeit with a detection limit corresponding to approximately 10(5) bacterial
      colony forming units (CFU) in this region. Vaccination of mice with heat killed
      streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI
      demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence
      emission over the course of nasopharyngeal infection. The work suggests the
      potential for BPI to be used in the non-invasive longitudinal evaluation of
      potential S. pyogenes vaccines. 

PMID- 24278475
TI  - FTO gene variant and risk of overweight and obesity among children and
      adolescents: a systematic review and meta-analysis.
AB  - OBJECTIVE: The fat mass and obesity associated gene (FTO) polymorphisms have been
      implicated in the susceptibility of overweight/obesity in children and
      adolescents. However, the results have been inconsistent. In this study, we
      performed a meta-analysis to clarify the association of FTO gene polymorphisms
      with overweight/obesity risk among children and adolescents. METHODS: PubMed and
      Embase were used to search for eligible published literatures. Pooled odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed
      effect models. RESULTS: A total of 21 articles containing 23 studies (11208cases
      and 35015controls) were included in our analysis. The results indicated that
      variant in FTO gene was significantly associated with increased risk of
      overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44;
      P<0.001). The overall pooled ORs for risk obesity and overweight were 1.34
      (95%CI: 1.21-1.48) and 1.35 (95%CI: 1.25-1.47), respectively. Subgroup analyses
      also showed similar trends in most subgroups of adjustment for covariates and
      unadjustment, different ethnicities (Caucasians, Asians, and Amerindians), and
      each of three investigated polymorphisms (rs9939609, rs1421085, and rs1558902).
      CONCLUSIONS: The present meta-analysis suggested a positive association between
      FTO gene polymorphism and overweight/obesity risk among children and adolescents.
      Further prospective studies should be recommended to confirm the observed
      association, and underlying mechanism should be investigated to clarify the
      association of FTO gene polymorphism with overweight/obesity.

PMID- 24278476
TI  - The expression of stlA in Photorhabdus luminescens is controlled by nutrient
      limitation.
AB  - Photorhabdus is a genus of Gram-negative entomopathogenic bacteria that also
      maintain a mutualistic association with nematodes from the family
      Heterorhabditis. Photorhabdus has an extensive secondary metabolism that is
      required for the interaction between the bacteria and the nematode. A major
      component of this secondary metabolism is a stilbene molecule, called ST. The
      first step in ST biosynthesis is the non-oxidative deamination of phenylalanine
      resulting in the production of cinnamic acid. This reaction is catalyzed by
      phenylalanine-ammonium lyase, an enzyme encoded by the stlA gene. In this study
      we show, using a stlA-gfp transcriptional fusion, that the expression of stlA is
      regulated by nutrient limitation through a regulatory network that involves at
      least 3 regulators. We show that TyrR, a LysR-type transcriptional regulator that
      regulates gene expression in response to aromatic amino acids in E. coli, is
      absolutely required for stlA expression. We also show that stlA expression is
      modulated by sigma(S) and Lrp, regulators that are implicated in the regulation
      of the response to nutrient limitation in other bacteria. This work is the first
      that describes pathway-specific regulation of secondary metabolism in
      Photorhabdus and, therefore, our study provides an initial insight into the
      complex regulatory network that controls secondary metabolism, and therefore
      mutualism, in this model organism. 

PMID- 24278477
TI  - TGF-beta regulates enamel mineralization and maturation through KLK4 expression.
AB  - Transforming growth factor-beta (TGF-beta) signaling plays an important role in
      regulating crucial biological processes such as cell proliferation,
      differentiation, apoptosis, and extracellular matrix remodeling. Many of these
      processes are also an integral part of amelogenesis. In order to delineate a
      precise role of TGF-beta signaling during amelogenesis, we developed a transgenic
      mouse line that harbors bovine amelogenin promoter-driven Cre recombinase, and
      bred this line with TGF-beta receptor II floxed mice to generate ameloblast
      specific TGF-beta receptor II conditional knockout (cKO) mice. Histological
      analysis of the teeth at postnatal day 7 (P7) showed altered enamel matrix
      composition in the cKO mice as compared to the floxed mice that had enamel
      similar to the wild-type mice. The uCT and SEM analyses revealed decreased
      mineral content in the cKO enamel concomitant with increased attrition and
      thinner enamel crystallites. Although the mRNA levels remained unaltered,
      immunostaining revealed increased amelogenin, ameloblastin, and enamelin
      localization in the cKO enamel at the maturation stage. Interestingly, KLK4 mRNA
      levels were significantly reduced in the cKO teeth along with a slight increase
      in MMP-20 levels, suggesting that normal enamel maturation is regulated by TGF
      beta signaling through the expression of KLK4. Thus, our study indicates that TGF
      beta signaling plays an important role in ameloblast functions and enamel
      maturation. 

PMID- 24278478
TI  - The 'Unicorn' dinosaur that wasn't: a new reconstruction of the crest of
      Tsintaosaurus and the early evolution of the lambeosaurine crest and rostrum.
AB  - The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed
      with an elevated, hollow, spike-like crest composed entirely of the nasal bones,
      although this has been disputed. Here, we provide a new reconstruction of the
      skull of this species based on reexamination and reinterpretation of the
      morphology and articular relationships of the type and Paratype skulls and a
      fragmentary crest. We confirm the presence of a supracranial crest composed of
      the elevated nasal bones, but also including the premaxillae. We hypothesize that
      the crest is a tall, lobate, hollow structure that projects dorsally and slightly
      caudally a distance greater than the height of the skull along the quadrate. In
      our reconstruction, the nasal passage passes through the crest, but enters the
      skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus
      spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies
      including a circumnarial fossa subdivided into three accessory fossae, prefrontal
      with ascending rostral process and lateral flange, nasals fused sagittally to
      form elongate tubular process that rises dorsally from skull roof, each nasal
      being expanded rostrocaudally into a rhomboid distal process, and medial
      processes of premaxillae at the summit of the cranial crest inserted between
      rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are
      present in more derived lambeosaurines (parasaurolophins and lambeosaurins), such
      as rotation of the caudal margin of the crest to an acute angle with the skull
      roof, lateral processes of the nasals that enclose part of the intracranial
      cavity and participate in the formation of the walls of the common median
      chamber, and a smooth narial fossa lacking ridges and accessory fossae. We
      hypothesize that ancestrally the rostrum of lambeosaurines may have been more
      similar to that in Saurolophinae, and became subsequently reduced in complexity
      during evolution of the group. 

PMID- 24278479
TI  - Extended duration of transgene expression from pegylated POD nanoparticles
      enables attenuation of photoreceptor degeneration.
AB  - Retinitis pigmentosa (RP) is the most genetically heterogeneous disorder known to
      cause blindness, involving over 50 different genes. Previously, we have described
      nanoparticles (NPs) 150 nm in size, comprised of a 3.5 kD peptide (POD) complexed
      to PEG and DNA (PEGPOD DNA). These NPs expressing GDNF enabled rescue of
      photoreceptor degeneration in mice up to 11 days post injection. In the current
      study we examine use of scaffold/ matrix attachment regions (S/MARs), CpG
      depletion and titration of DNA content of PEGPOD DNA NPs to extend the duration
      of transgene expression. S/MARs and CpGs did not significantly influence the
      duration of transgene expression, but did influence its stability. These
      parameters enabled us to extend transgene expression from 48 hours to 10 weeks.
      At 77 days post injection, we observed a 76% rescue of the thickness of the
      retinal outer nuclear layer (ONL) and at 37 days post injection we observed 53%
      and 55% rescue of the A and B wave ERG amplitudes respectively and 60% rescue of
      the ONL. Our studies suggest that PEGPOD DNA NPs have potential as gene delivery
      vectors for the retina. 

PMID- 24278480
TI  - A microfluidic, high throughput protein crystal growth method for microgravity.
AB  - The attenuation of sedimentation and convection in microgravity can sometimes
      decrease irregularities formed during macromolecular crystal growth. Current
      terrestrial protein crystal growth (PCG) capabilities are very different than
      those used during the Shuttle era and that are currently on the International
      Space Station (ISS). The focus of this experiment was to demonstrate the use of a
      commercial off-the-shelf, high throughput, PCG method in microgravity. Using
      Protein BioSolutions' microfluidic Plug MakerTM/CrystalCardTM system, we tested
      the ability to grow crystals of the regulator of glucose metabolism and
      adipogenesis: peroxisome proliferator-activated receptor gamma (apo-hPPAR-gamma
      LBD), as well as several PCG standards. Overall, we sent 25 CrystalCardsTM to the
      ISS, containing ~10,000 individual microgravity PCG experiments in a 3U NanoRacks
      NanoLab (1U = 10(3) cm.). After 70 days on the ISS, our samples were returned
      with 16 of 25 (64%) microgravity cards having crystals, compared to 12 of 25
      (48%) of the ground controls. Encouragingly, there were more apo-hPPAR-gamma LBD
      crystals in the microgravity PCG cards than the 1g controls. These positive
      results hope to introduce the use of the PCG standard of low sample volume and
      large experimental density to the microgravity environment and provide new
      opportunities for macromolecular samples that may crystallize poorly in standard
      laboratories. 

PMID- 24278481
TI  - Dietary omega-3 polyunsaturated fatty acids alter the fatty acid composition of
      hepatic and plasma bioactive lipids in C57BL/6 mice: a lipidomic approach.
AB  - BACKGROUND: Omega (n)-3 polyunsaturated fatty acids (PUFA) are converted to
      bioactive lipid components that are important mediators in metabolic and
      physiological pathways; however, which bioactive compounds are metabolically
      active, and their mechanisms of action are still not clear. We investigated using
      lipidomic techniques, the effects of diets high in n-3 PUFA on the fatty acid
      composition of various bioactive lipids in plasma and liver. METHODOLOGY AND
      PRINCIPAL FINDINGS: Female C57BL/6 mice were fed semi-purified diets (20% w/w
      fat) containing varying amounts of n-3 PUFA before mating, during gestation and
      lactation, and until weaning. Male offspring were continued on their mothers'
      diets for 16 weeks. Hepatic and plasma lipids were extracted in the presence of
      non-naturally occurring internal standards, and tandem electrospray ionization
      mass spectrometry methods were used to measure the fatty acyl compositions. There
      was no significant difference in total concentrations of phospholipids in both
      groups. However, there was a significantly higher concentration of
      eicosapentaenoic acid containing phosphatidylcholine (PC),
      lysophosphatidylcholine (LPC), and cholesteryl esters (CE) (p < 0.01) in the high
      n-3 PUFA group compared to the low n-3 PUFA group in both liver and plasma.
      Plasma and liver from the high n-3 PUFA group also had a higher concentration of
      free n-3 PUFA (p < 0.05). There were no significant differences in plasma
      concentrations of different fatty acyl species of phosphatidylethanolamine,
      triglycerides, sphingomyelin and ceramides. CONCLUSIONS/SIGNIFICANCE: Our
      findings reveal for the first time that a diet high in n-3 PUFA caused enrichment
      of n-3 PUFA in PC, LPC, CE and free fatty acids in the plasma and liver of
      C57BL/6 mice. PC, LPC, and unesterified free n-3 PUFA are important bioactive
      lipids, thus altering their fatty acyl composition will have important metabolic
      and physiological roles.

PMID- 24278482
TI  - Decorin mimic inhibits vascular smooth muscle proliferation and migration.
AB  - Over the past 10 years, the number of percutaneous coronary intervention
      procedures performed in the United States increased by 33%; however, restenosis,
      which inhibits complete functional recovery of the vessel wall, complicates this
      procedure. A wide range of anti-restenotic therapeutics have been developed,
      although many elicit non-specific effects that compromise vessel healing. Drawing
      inspiration from biologically-relevant molecules, our lab developed a mimic of
      the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen
      and thereby effectively decrease platelet activation, thus contributing to
      suppression of vascular intimal hyperplasia. Here, we characterize the effects of
      DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential
      impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo
      platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro
      inflammatory cytokine secretion in vitro in a concentration dependent manner as
      compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures
      decreased SMC migration and protein synthesis by 95% and 37%, respectively.
      Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal
      hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS
      SILY demonstrates multiple biological activities that may all synergistically
      contribute to an improved treatment paradigm for balloon angioplasty. 

PMID- 24278483
TI  - The contribution of lysosomotropism to autophagy perturbation.
AB  - Autophagy refers to the catabolic process in eukaryotic cells that delivers
      cytoplasmic material to lysosomes for degradation. This highly conserved process
      is involved in the clearance of long-lived proteins and damaged organelles.
      Consequently, autophagy is important in providing nutrients to maintain cellular
      function under starvation, maintaining cellular homeostasis, and promoting cell
      survival under certain conditions. Several pathways, including mTOR, have been
      shown to regulate autophagy. However, the impact of lysosomal function impairment
      on the autophagy process has not been fully explored. Basic lipophilic compounds
      can accumulate in lysosomes via pH partitioning leading to perturbation of
      lysosomal function. Our hypothesis is that these types of compounds can disturb
      the autophagy process. Eleven drugs previously shown to accumulate in lysosomes
      were selected and evaluated for their effects on cytotoxicity and autophagy using
      ATP depletion and LC3 assessment, respectively. All eleven drugs induced
      increased staining of endogenous LC3 and exogenous GFP-LC3, even at non toxic
      dose levels. In addition, an increase in the abundance of SQSTM1/p62 by all
      tested compounds denotes that the increase in LC3 is due to autophagy
      perturbation rather than enhancement. Furthermore, the gene expression profile
      resulting from in vitro treatment with these drugs revealed the suppression of
      plentiful long-lived proteins, including structural cytoskeletal and associated
      proteins, and extracellular matrix proteins. This finding indicates a retardation
      of protein turnover which further supports the notion of autophagy inhibition.
      Interestingly, upregulation of genes containing antioxidant response elements,
      e.g. glutathione S transferase and NAD(P)H dehydrogenase quinone 1 was observed,
      suggesting activation of Nrf2 transcription factor. These gene expression changes
      could be related to an increase in SQSTM1/p62 resulting from autophagy
      deficiency. In summary, our data indicate that lysosomal accumulation due to the
      basic lipophilic nature of xenobiotics could be a general mechanism contributing
      to the perturbation of the autophagy process. 

PMID- 24278484
TI  - Reciprocal regulation of development of neutrophil-dendritic cell hybrids in mice
      by IL-4 and interferon-gamma.
AB  - Neutrophils contribute to innate host immunity by functioning as professional
      phagocytes, whereas dendritic cells (DCs) are prototypic antigen presenting cells
      (APCs) responsible for the induction of adaptive immune responses. We have
      demonstrated recently that neutrophils trans-differentiate into a unique
      population, termed "neutrophil-DC hybrids," expressing surface markers of both
      neutrophils and DCs and exhibiting dual functionality of both phagocytes and
      APCs. Although the hybrid cells emerged in significant numbers in murine bone
      marrow (BM) culture in the presence of GM-CSF, mechanisms regulating their
      development remained mostly unknown. In this study, we tested a total of 61
      cytokines for their potentials to regulate neutrophil-DC hybrid formation using a
      newly developed BM micro-culture system combined with semi-automated FACS
      analysis. Several cytokines including GM-CSF were found to promote the generation
      of neutrophil-DC hybrids defined by the phenotype of CD11c(+)/MHC II(+)/Ly6G(+).
      When tested in the presence of GM-CSF, hybrid cell development was enhanced by IL
      4 and suppressed by interferon-gamma (IFNgamma) in dose-dependent fashions. We
      next determined in vivo impacts of IL-4 and IFNgamma on the development of
      neutrophil-DC hybrids in thioglycollate-induced peritonitis lesions.
      Intraperitoneal administrations of IL-4/anti-IL-4 antibody complex (IL-4C)
      significantly increased the number of hybrids recovered from the lesions. By
      contract, recovery of hybrids was reduced by recombinant IFNgamma. With regard to
      function, those hybrid cells recovered from IL-4C-treated mice and IFNgamma
      treated mice showed potent abilities to capture E.coli. These observations imply
      that emergence of neutrophil-DC hybrids in inflammatory sites is tightly
      regulated by local cytokine milieus. 

PMID- 24278485
TI  - Disseminated histoplasmosis in HIV-infected patients in South America: a
      neglected killer continues on its rampage.

PMID- 24278486
TI  - A review of factors that influence individual compliance with mass drug
      administration for elimination of lymphatic filariasis.
AB  - BACKGROUND: The success of programs to eliminate lymphatic filariasis (LF)
      depends in large part on their ability to achieve and sustain high levels of
      compliance with mass drug administration (MDA). This paper reports results from a
      comprehensive review of factors that affect compliance with MDA.
      METHODOLOGY/PRINCIPAL FINDINGS: Papers published between 2000 and 2012 were
      considered, and 79 publications were included in the final dataset for analysis
      after two rounds of selection. While results varied in different settings, some
      common features were associated with successful programs and with compliance by
      individuals. Training and motivation of drug distributors is critically
      important, because these people directly interact with target populations, and
      their actions can affect MDA compliance decisions by families and individuals.
      Other important programmatic issues include thorough preparation of personnel,
      supplies, and logistics for implementation and preparation of the population for
      MDA. Demographic factors (age, sex, income level, and area of residence) are
      often associated with compliance by individuals, but compliance decisions are
      also affected by perceptions of the potential benefits of participation versus
      the risk of adverse events. Trust and information can sometimes offset fear of
      the unknown. While no single formula can ensure success MDA in all settings, five
      key ingredients were identified: engender trust, tailor programs to local
      conditions, take actions to minimize the impact of adverse events, promote the
      broader benefits of the MDA program, and directly address the issue of systematic
      non-compliance, which harms communities by prolonging their exposure to LF.
      CONCLUSIONS/SIGNIFICANCE: This review has identified factors that promote
      coverage and compliance with MDA for LF elimination across countries. This
      information may be helpful for explaining results that do not meet expectations
      and for developing remedies for ailing MDA programs. Our review has also
      identified gaps in understanding and suggested priority areas for further
      research.

PMID- 24278488
TI  - Pioneering neglected disease research in southern Mexico at the "Dr. Hideyo
      Noguchi" regional research center.

PMID- 24278487
TI  - Whole genome sequencing of field isolates reveals a common duplication of the
      Duffy binding protein gene in Malagasy Plasmodium vivax strains.
AB  - BACKGROUND: Plasmodium vivax is the most prevalent human malaria parasite,
      causing serious public health problems in malaria-endemic countries. Until
      recently the Duffy-negative blood group phenotype was considered to confer
      resistance to vivax malaria for most African ethnicities. We and others have
      reported that P. vivax strains in African countries from Madagascar to Mauritania
      display capacity to cause clinical vivax malaria in Duffy-negative people. New
      insights must now explain Duffy-independent P. vivax invasion of human
      erythrocytes. METHODS/PRINCIPAL FINDINGS: Through recent whole genome sequencing
      we obtained >= 70* coverage of the P. vivax genome from five field-isolates,
      resulting in >= 93% of the Sal I reference sequenced at coverage greater than
      20*. Combined with sequences from one additional Malagasy field isolate and from
      five monkey-adapted strains, we describe here identification of DNA sequence
      rearrangements in the P. vivax genome, including discovery of a duplication of
      the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients
      infected with P. vivax showed that the PvDBP duplication was present in numerous
      locations in Madagascar and found in over 50% of infected patients evaluated.
      Extended geographic surveys showed that the PvDBP duplication was detected
      frequently in vivax patients living in East Africa and in some residents of non
      African P. vivax-endemic countries. Additionally, the PvDBP duplication was
      observed in travelers seeking treatment of vivax malaria upon returning home.
      PvDBP duplication prevalence was highest in west-central Madagascar sites where
      the highest frequencies of P. vivax-infected, Duffy-negative people were
      reported. CONCLUSIONS/SIGNIFICANCE: The highly conserved nature of the sequence
      involved in the PvDBP duplication suggests that it has occurred in a recent
      evolutionary time frame. These data suggest that PvDBP, a merozoite surface
      protein involved in red cell adhesion is rapidly evolving, possibly in response
      to constraints imposed by erythrocyte Duffy negativity in some human populations.

PMID- 24278489
TI  - Isolation of saint louis encephalitis virus from a horse with neurological
      disease in Brazil.
AB  - St. Louis encephalitis virus (SLEV) is a causative agent of encephalitis in
      humans in the Western hemisphere. SLEV is a positive-sense RNA virus that belongs
      to the Flavivirus genus, which includes West Nile encephalitis virus, Japanese
      encephalitis virus, Dengue virus and other medically important viruses. Recently,
      we isolated a SLEV strain from the brain of a horse with neurological signs in
      the countryside of Minas Gerais, Brazil. The SLEV isolation was confirmed by
      reverse-transcription RT-PCR and sequencing of the E protein gene. Virus identity
      was also confirmed by indirect immunofluorescence using commercial antibodies
      against SLEV. To characterize this newly isolated strain in vivo, serial passages
      in newborn mice were performed and led to hemorrhagic manifestations associated
      with recruitment of inflammatory cells into the central nervous system of
      newborns. In summary this is the first isolation of SLEV from a horse with
      neurological signs in Brazil. 

PMID- 24278490
TI  - Severe South American ocular toxoplasmosis is associated with decreased Ifn
      gamma/Il-17a and increased Il-6/Il-13 intraocular levels.
AB  - In a cross sectional study, 19 French and 23 Colombian cases of confirmed active
      ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical,
      parasitological and immunological responses and relate them to the infecting
      strains. A complete ocular examination was performed in each patient. The
      infecting strain was characterized by genotyping when intraocular Toxoplasma DNA
      was detectable, as well as by peptide-specific serotyping for each patient. To
      characterize the immune response, we assessed Toxoplasma protein recognition
      patterns by intraocular antibodies and the intraocular profile of cytokines,
      chemokines and growth factors. Significant differences were found for size of
      active lesions, unilateral macular involvement, unilateral visual impairment,
      vitreous inflammation, synechiae, and vasculitis, with higher values observed
      throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was
      only successful in three Colombian patients revealing one type I and two atypical
      strains. The Colombian OT patients possessed heterogeneous atypical serotypes
      whereas the French were uniformly reactive to type II strain peptides. The
      protein patterns recognized by intraocular antibodies and the cytokine patterns
      were strikingly different between the two populations. Intraocular IFN-gamma and
      IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected
      in aqueous humor of Colombian patients. Our results are consistent with the
      hypothesis that South American strains may cause more severe OT due to an
      inhibition of the protective effect of IFN-gamma. 

PMID- 24278491
TI  - Molecular cloning and characterization of taurocyamine kinase from Clonorchis
      sinensis: a candidate chemotherapeutic target.
AB  - BACKGROUND: Adult Clonorchis sinensis lives in the bile duct and causes endemic
      clonorchiasis in East Asian countries. Phosphagen kinases (PK) constitute a
      highly conserved family of enzymes, which play a role in ATP buffering in cells,
      and are potential targets for chemotherapeutic agents, since variants of PK are
      found only in invertebrate animals, including helminthic parasites. This work is
      conducted to characterize a PK from C. sinensis and to address further
      investigation for future drug development. METHODOLOGY/PRINCIPAL FINDINGS:
      [corrected] A cDNA clone encoding a putative polypeptide of 717 amino acids was
      retrieved from a C. sinensis transcriptome. This polypeptide was homologous to
      taurocyamine kinase (TK) of the invertebrate animals and consisted of two
      contiguous domains. C. sinensis TK (CsTK) gene was reported and found consist of
      13 exons intercalated with 12 introns. This suggested an evolutionary pathway
      originating from an arginine kinase gene group, and distinguished annelid TK from
      the general CK phylogenetic group. CsTK was found not to have a homologous
      counterpart in sequences analysis of its mammalian hosts from public databases.
      Individual domains of CsTK, as well as the whole two-domain enzyme, showed
      enzymatic activity and specificity toward taurocyamine substrate. Of the CsTK
      residues, R58, I60 and Y84 of domain 1, and H60, I63 and Y87 of domain 2 were
      found to participate in binding taurocyamine. CsTK expression was distributed in
      locomotive and reproductive organs of adult C. sinensis. Developmentally, CsTK
      was stably expressed in both the adult and metacercariae stages. Recombinant CsTK
      protein was found to have low sensitivity and specificity toward C. sinensis and
      platyhelminth-infected human sera on ELISA. CONCLUSION: CsTK is a promising anti
      C. sinensis drug target since the enzyme is found only in the C. sinensis and has
      a substrate specificity for taurocyamine, which is different from its mammalian
      counterpart, creatine.

PMID- 24278492
TI  - Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco,
      Puebla State, Mexico: epidemiology and treatment with nitazoxanide.
AB  - BACKGROUND: The Atlixco municipality, Puebla State, at a mean altitude of 1840 m,
      was selected for a study of Fasciola hepatica infection in schoolchildren in
      Mexico. This area presents permanent water collections continuously receiving
      thaw water from Popocatepetl volcano (5426 m altitude) through the community
      supply channels, conforming an epidemiological scenario similar to those known in
      hyperendemic areas of Andean countries. METHODOLOGY AND FINDINGS: A total of 865
      6-14 year-old schoolchildren were analyzed with FasciDIG coproantigen test and
      Lumbreras rapid sedimentation technique, and quantitatively assessed with Kato
      Katz. Fascioliasis prevalences ranged 2.94-13.33% according to localities (mean
      5.78%). Intensities were however low (24-384 epg). The association between
      fascioliasis and the habit of eating raw vegetables was identified, including
      watercress and radish with pronouncedly higher relative risk than lettuce,
      corncob, spinach, alfalfa juice, and broccoli. Many F. hepatica-infected children
      were coinfected by other parasites. Entamoeba histolytica/dispar, Giardia
      intestinalis, Blastocystis hominis, Hymenolepis nana and Ascaris lumbricoides
      infection resulted in risk factors for F. hepatica infection. Nitazoxanide
      efficacy against fascioliasis was 94.0% and 100% after first and second treatment
      courses, respectively. The few children, for whom a second treatment course was
      needed, were concomitantly infected by moderate ascariasis burdens. Its efficacy
      was also very high in the treatment of E. histolytica/E. dispar, G. intestinalis,
      B. hominis, H. nana, A. lumbricoides, Trichuris trichiura, and Enterobius
      vermicularis. A second treatment course was needed for all children affected by
      ancylostomatids. CONCLUSIONS: Fascioliasis prevalences indicate this area to be
      mesoendemic, with isolated hyperendemic foci. This is the first time that a human
      fascioliasis endemic area is described in North America. Nitazoxanide appears as
      an appropriate alternative to triclabendazole, the present drug of choice for
      chronic fascioliasis. Its wide spectrum efficacy against intestinal protozooses
      and helminthiasis, usually coinfecting liver fluke infected subjects in human
      endemic areas, represents an important added value.

PMID- 24278493
TI  - Ultra-deep sequencing of intra-host rabies virus populations during cross-species
      transmission.
AB  - One of the hurdles to understanding the role of viral quasispecies in RNA virus
      cross-species transmission (CST) events is the need to analyze a densely sampled
      outbreak using deep sequencing in order to measure the amount of mutation
      occurring on a small time scale. In 2009, the California Department of Public
      Health reported a dramatic increase (350) in the number of gray foxes infected
      with a rabies virus variant for which striped skunks serve as a reservoir host in
      Humboldt County. To better understand the evolution of rabies, deep-sequencing
      was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For
      each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced
      using the Illumina platform. Average coverage was 17,448 and this allowed
      characterization of the rabies virus population present in each sample at
      unprecedented depths. Phylogenetic analysis of the consensus sequence data
      demonstrated that samples clustered according to date (1995 vs. 2009) and
      geographic location (northern vs. southern). A single amino acid change in the G
      protein distinguished a subset of northern foxes from a haplotype present in both
      foxes and skunks, suggesting this mutation may have played a role in the observed
      increased transmission among foxes in this region. Deep-sequencing data indicated
      that many genetic changes associated with the CST event occurred prior to 2009
      since several nonsynonymous mutations that were present in the consensus
      sequences of skunk and fox rabies samples obtained from 20032010 were present at
      the sub-consensus level (as rare variants in the viral population) in skunk and
      fox samples from 1995. These results suggest that analysis of rare variants
      within a viral population may yield clues to ancestral genomes and identify rare
      variants that have the potential to be selected for if environment conditions
      change. 

PMID- 24278494
TI  - Recent emergence and spread of an Arctic-related phylogenetic lineage of rabies
      virus in Nepal.
AB  - Rabies is a zoonotic disease that is endemic in many parts of the developing
      world, especially in Africa and Asia. However its epidemiology remains largely
      unappreciated in much of these regions, such as in Nepal, where limited
      information is available about the spatiotemporal dynamics of the main
      etiological agent, the rabies virus (RABV). In this study, we describe for the
      first time the phylogenetic diversity and evolution of RABV circulating in Nepal,
      as well as their geographical relationships within the broader region. A total of
      24 new isolates obtained from Nepal and collected from 2003 to 2011 were full
      length sequenced for both the nucleoprotein and the glycoprotein genes, and
      analysed using neighbour-joining and maximum-likelihood phylogenetic methods with
      representative viruses from all over the world, including new related RABV
      strains from neighbouring or more distant countries (Afghanistan, Greenland,
      Iran, Russia and USA). Despite Nepal's limited land surface and its particular
      geographical position within the Indian subcontinent, our study revealed the
      presence of a surprising wide genetic diversity of RABV, with the co-existence of
      three different phylogenetic groups: an Indian subcontinent clade and two
      different Arctic-like sub-clades within the Arctic-related clade. This
      observation suggests at least two independent episodes of rabies introduction
      from neighbouring countries. In addition, specific phylogenetic and temporal
      evolution analysis of viruses within the Arctic-related clade has identified a
      new recently emerged RABV lineage we named as the Arctic-like 3 (AL-3) sub-clade
      that is already widely spread in Nepal. 

PMID- 24278495
TI  - Gene amplification and point mutations in pyrimidine metabolic genes in 5
      fluorouracil resistant Leishmania infantum.
AB  - BACKGROUND: The human protozoan parasites Leishmania are prototrophic for
      pyrimidines with the ability of both de novo biosynthesis and uptake of
      pyrimidines. METHODOLOGY/PRINCIPAL FINDINGS: Five independent L. infantum mutants
      were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in
      the hope to better understand the metabolism of pyrimidine in Leishmania.
      Analysis of the 5-FU mutants by comparative genomic hybridization and whole
      genome sequencing revealed in selected mutants the amplification of DHFR-TS and a
      deletion of part of chromosome 10. Point mutations in uracil phosphorybosyl
      transferase (UPRT), thymidine kinase (TK) and uridine phosphorylase (UP) were
      also observed in three individual resistant mutants. Transfection experiments
      confirmed that these point mutations were responsible for 5-FU resistance.
      Transport studies revealed that one resistant mutant was defective for uracil and
      5-FU import. CONCLUSION/SIGNIFICANCE: This study provided further insights in
      pyrimidine metabolism in Leishmania and confirmed that multiple mutations can co
      exist and lead to resistance in Leishmania.

PMID- 24278496
TI  - NTDs V.2.0: "blue marble health"--neglected tropical disease control and
      elimination in a shifting health policy landscape.
AB  - The concept of the neglected tropical diseases (NTDs) was established in the
      aftermath of the Millennium Development Goals. Here, we summarize the emergence
      of several new post-2010 global health documents and policies, and how they may
      alter the way we frame the world's major NTDs since they were first highlighted.
      These documents include a new Global Burden of Disease 2010 Study that identifies
      visceral leishmaniasis and food-borne trematode infections as priority diseases
      beyond the seven NTDs originally targeted by preventive chemotherapy, a London
      Declaration for access to essential medicines, and a 2013 World Health Assembly
      resolution on NTDs. Additional information highlights an emerging dengue fever
      pandemic. New United Nations resolutions on women and the non-communicable
      diseases (NCDs) have not yet embraced NTDs, which may actually be the most common
      afflictions of girls and women and represent a stealth cause of NCDs. NTDs also
      have important direct and collateral effects on HIV/AIDS and malaria, and there
      is now a robust evidence base and rationale for incorporating NTDs into the
      Global Fund to Fight AIDS, Tuberculosis, and Malaria. "Blue marble health" is an
      added concept that recognizes a paradoxical NTD disease burden among the poor
      living in G20 (Group of Twenty) and other wealthy countries, requiring these
      nations to take greater ownership for both disease control and research and
      development. As we advance past the year 2015, it will be essential to
      incorporate global NTD elimination into newly proposed Sustainable Development
      Goals. 

PMID- 24278497
TI  - Highly sensitive in vivo imaging of Trypanosoma brucei expressing "red-shifted"
      luciferase.
AB  - BACKGROUND: Human African trypanosomiasis is caused by infection with parasites
      of the Trypanosoma brucei species complex, and threatens over 70 million people
      in sub-Saharan Africa. Development of new drugs is hampered by the limitations of
      current rodent models, particularly for stage II infections, which occur once
      parasites have accessed the CNS. Bioluminescence imaging of pathogens expressing
      firefly luciferase (emission maximum 562 nm) has been adopted in a number of in
      vivo models of disease to monitor dissemination, drug-treatment and the role of
      immune responses. However, lack of sensitivity in detecting deep tissue
      bioluminescence at wavelengths below 600 nm has restricted the wide-spread use of
      in vivo imaging to investigate infections with T. brucei and other
      trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a system that
      allows the detection of fewer than 100 bioluminescent T. brucei parasites in a
      murine model. As a reporter, we used a codon-optimised red-shifted Photinus
      pyralis luciferase (PpyRE9H) with a peak emission of 617 nm. Maximal expression
      was obtained following targeted integration of the gene, flanked by an upstream
      5'-variant surface glycoprotein untranslated region (UTR) and a downstream 3'
      tubulin UTR, into a T. brucei ribosomal DNA locus. Expression was stable in the
      absence of selective drug for at least 3 months and was not associated with
      detectable phenotypic changes. Parasite dissemination and drug efficacy could be
      monitored in real time, and brain infections were readily detectable. The level
      of sensitivity in vivo was significantly greater than achievable with a yellow
      firefly luciferase reporter. CONCLUSIONS/SIGNIFICANCE: The optimised
      bioluminescent reporter line described here will significantly enhance the
      application of in vivo imaging to study stage II African trypanosomiasis in
      murine models. The greatly increased sensitivity provides a new framework for
      investigating host-parasite relationships, particularly in the context of CNS
      infections. It should be ideally suited to drug evaluation programmes.

PMID- 24278498
TI  - Cholera vaccination campaign contributes to improved knowledge regarding cholera
      and improved practice relevant to waterborne disease in rural Haiti.
AB  - BACKGROUND: Haiti's cholera epidemic has been devastating partly due to
      underlying weak infrastructure and limited clean water and sanitation. A
      comprehensive approach to cholera control is crucial, yet some have argued that
      oral cholera vaccination (OCV) might result in reduced hygiene practice among
      recipients. We evaluated the impact of an OCV campaign on knowledge and health
      practice in rural Haiti. METHODOLOGY/PRINCIPAL FINDINGS: We administered baseline
      surveys on knowledge and practice relevant to cholera and waterborne disease to
      every 10th household during a census in rural Haiti in February 2012 (N = 811).
      An OCV campaign occurred from May-June 2012 after which we administered identical
      surveys to 518 households randomly chosen from the same region in September 2012.
      We compared responses pre- and post-OCV campaign. Post-vaccination, there was
      improved knowledge with significant increase in percentage of respondents with >=
      3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95%
      confidence interval[CI] 1.52-2.40), preventive methods (OR 1.83; 95% CI 1.46
      2.30), and water treatment modalities (OR 2.75; 95% CI 2.16-3.50). Relative to
      pre-vaccination, participants were more likely post-OCV to report always treating
      water (OR 1.62; 95% CI 1.28-2.05). Respondents were also more likely to report
      hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI
      1.03-1.64). Knowledge of treating water as a cholera prevention measure was
      associated with practice of always treating water (OR 1.47; 95% CI 1.14-1.89).
      Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47;
      95% CI 1.35-4.51). CONCLUSION: An OCV campaign in rural Haiti was associated with
      significant improvement in cholera knowledge and practices related to waterborne
      disease. OCV can be part of comprehensive cholera control and reinforce, not
      detract from, other control efforts in Haiti.

PMID- 24278499
TI  - Applications of genetically modified tools to safety assessment in drug
      development.
AB  - The process of new drug development consists of several stages; after identifying
      potential candidate compounds, preclinical studies using animal models link the
      laboratory and human clinical trials. Among many steps in preclinical studies,
      toxicology and safety assessments contribute to identify potential adverse events
      and provide rationale for setting the initial doses in clinical trials. Gene
      modulation is one of the important tools of modern biology, and is commonly
      employed to examine the function of genes of interest. Advances in new drug
      development have been achieved by exploding information on target selection and
      validation using genetically modified animal models as well as those of cells. In
      this review, a recent trend of genetically modified methods is discussed with
      reference to safety assessments, and the exemplary applications of gene
      modulating tools to the tests in new drug development were summarized. 

PMID- 24278500
TI  - Assessment of the dermal and ocular irritation potential of lomefloxacin by using
      in vitro methods.
AB  - The evaluation of eye and skin irritation potential is essential to ensuring the
      safety of human in contact with a wide variety of substances. Despite this
      importance of irritation test, little is known with respect to the irritation
      potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to
      cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate
      the tendency of lomefloxacin to cause eye and skin irritation, we carried out in
      vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test
      using KeraSkin(TM) human skin model system. 3T3 neutral red uptake assay has been
      proposed as a potential replacement alternative for the Draize Eye irritation
      test. In this study, the IC50 value obtained for lomefloxacin was 375 MUg.
      According to the classification model used for determining in vitro categories,
      lomefloxacin was classified as moderately irritant. For evaluation of skin
      irritation, engineered epidermal equivalents (KeraSkin(TM)) were subjected to 10
      and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue
      viability evaluation, and by the release of a pro-inflammatory mediator,
      interleukin-1alpha. Lomefloxacin increased the interleukin-1alpha release after
      15 minutes of exposure and 42 hours of post incubation, although no decrease in
      viability was observed. Therefore, lomefloxacin is considered to be moderately
      irritant to skin and eye. 

PMID- 24278501
TI  - Identification of differentially expressed genes in human mesenchymal stem cell
      derived neurons.
AB  - Mesenchymal stem cells (MSCs) have greater potential for immediate clinical and
      toxicological applications, due to their ability to self-renew, proliferate, and
      differentiate into a variety of cell types. To identify novel candidate genes
      that were specifically expressed during transdifferentiation of human MSCs to
      neuronal cells, we performed a differential expression analysis with random
      priming approach using annealing control primer-based differential display
      reverse transcription-polymerase chain reaction approach. We identified genes for
      acyl-CoA thioesterase, tissue inhibitor of metalloproteinases-1, brain glycogen
      phosphorylase, ubiquitin C-terminal hydrolase and aldehyde reductase were up
      regualted, whereas genes for transgelin and heparan sulfate proteoglycan were
      down-regulated in MSC-derived neurons. These differentially expressed genes may
      have potential role in regulation of neurogenesis. This study could be applied to
      environmental toxicology in the field of testing the toxicity of a chemical or a
      physical agent. 

PMID- 24278502
TI  - Gene expression analysis of so called asian dust extracts in human acute myeloid
      leukemia cells.
AB  - As the frequency and the intensity of so called Asian dust (AD) events have
      increased, public concerns about the adverse health effects has spiked sharply
      over the last two decades. Despite the recent reports on the correlation between
      AD events and the risk for cardiovascular and respiratory disease, the nature of
      the toxicity and the degree of the risk are yet largely unknown. In the present
      study, we investigated the effects of the dichloromethane extract of AD (AD-X)
      and that of urban dust (NAD-X) collected during a non-AD period on gene
      expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips.
      Global changes in gene expression were analyzed after 24 h of incubation with 50
      or 100 MUg/ml AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and
      Benjamini-Hochberg multiple testing correction for false discovery rate of the
      results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive,
      respectively. The genes were classified into three groups by Venn diagram
      analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific,
      and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the
      expression levels of the selected genes. The expression patterns of five genes,
      namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the
      two groups. Following rigorous validation process, these genes may provide
      information in developing biomarker for AD exposure. 

PMID- 24278503
TI  - Antimutagenic and Anticarcinogenic Effect of Methanol Extracts of Sweetpotato
      (Ipomea batata) Leaves.
AB  - The present study was conducted to investigate the antimutagenic potential of the
      methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the
      SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The
      anticarcinogenic effects were also studied by calculation of the IC50 on human
      cancer cell lines and investigating the function of gap junction in rat liver
      epithelial cells. The IB extract inhibited dose-dependently the beta
      galactosidase activity induced spontaneously at concentration of more than 200
      mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01)
      the beta-galactosidase activities induced by mutagen 6-chloro-9-[3- (2
      chloroethylamino) proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of
      more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous
      reversions of S. typhimurium TA 98 and 100 but benzo (alpha) pyrene (BaP) 
      stimulated reversions were decreased dose-dependently (p < 0.01) at the
      concentration of more than 100 mg/ml. The IC50 value of stomach cancer cells was
      lower than that of normal rat liver epithelial cells, but the values of colon and
      uterine cancer cell lines were similar to those of normal rat liver epithelial
      cells. The transfer of dye through gap junctions was not affected by treatment of
      the IB extracts at any concentration during treatment periods. The simultaneously
      treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA)
      effectively prevented the inhibition of dye transfer induced by TPA 1 hour after
      treatment at all exposed concentrations. The number of gap junctions was
      significantly (p < 0.01) increased by the treatment with IB extract at
      concentrations of more than 40 MUg/ml. The inhibition of the expression of gap
      junction proteins by TPA (0.01 MUg/ml) was recovered dose dependently by the
      simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has
      antimutagenic and anticarcionogenic activity in vitro. 

PMID- 24278504
TI  - Methanolic Extract of Asterina pectinifera inhibits LPS-Induced Inflammatory
      Mediators in Murine Macrophage.
AB  - This study aimed to elucidate anti-inflammatory activities from extracts of
      Asterina pectinifera on nitric oxide (NO) production, TNF-alpha and IL-6 release
      in lipopolysaccharide (LPS) -stimulated murine macrophage cell, RAW264.7. We
      prepared the methanolic extracts (60-MAP, 70-MAP, 80-MAP and 90-MAP) , aqueous
      extract (W-AP) and functional bioactive compound fraction (He-AP and EA-AP) from
      Asterina pectinifera according to extract method. The 60-MAP, 70-MAP, 80-MAP, 90
      MAP and W-AP were significantly suppressed LPS-induced production NO, TNF-alpha
      and IL-6 secretion in a concentration-dependent manner (P < 0.05) . Especially,
      80-MAP by extracted 80% methanol had the strongest activity in reduction of
      inflammatory mediators among these extracts. Indeed, to identify active fraction,
      which contained potential bioactive compounds, from 80-MAP of Asterina
      pectinifera, we tested anti-inflammatory activity of the He-AP or the EA-AP. The
      He-AP was next extracted from 80-MAP and the EA-AP were extracted from the other
      methanol layer except the He-AP. The EA-AP demonstrated a strong anti
      inflammatory effect through its ability to reduce NO production and it also
      inhibited the production of proinflammatory cytokines such as IL-6 and TNF-alpha
      at low concentration. These results suggested that the methanolic extract from
      Asterina pectinifera had the potential inhibitory effects on the production of
      these inflammatory mediators. 

PMID- 24278505
TI  - Cloning and Expression in Pichia pastoris of a New Cytochrome P450 Gene from a
      Dandruff-causing Malassezia globosa.
AB  - The Malassezia fungi are responsible for various human skin disorders including
      dandruff and seborrheic dermatitis. Of the Malassezia fungi, Malassezia globosa
      (M. globosa) is one of the most common in human scalp. The completed genome
      sequence of M. globosa contains four putative cytochrome P450 genes. To determine
      the roles of Malassezia P450 enzymes in the biosynthesis of ergosterol, we
      isolated MGL3996 gene from M. globosa chromosomal DNA by PCR. The MGL3996 gene
      encodes an enzyme of 616 amino acids, which shows strong similarity with known
      CYP52s of other species. MGL3996 gene was cloned and expressed in Pichia pastoris
      (P. pastoris) heterologous yeast expression system. Using the yeast microsomes
      expressing MGL3996 protein, a typical P450 CO-difference spectrum was shown with
      absorption maximum at 448 nm. SDS-PAGE analysis revealed a protein band of
      apparent molecular weight 69 kDa and Western blot with anti-histidine tag
      antibody showed that MGL3996 was successfully expressed in P. pastoris. Cloning
      and expression of a new P450 gene is an important step to study the P450
      monooxygenase system of M. globosa and to understand the role of P450 enzymes in
      pathophysiology of dandruff. 

PMID- 24278506
TI  - Mouse Single Oral Dose Toxicity Study of DHU001, a Polyherbal Formula.
AB  - This study was conducted to obtain acute information of the oral dose toxicity of
      DHU001, a polyherbal formula in male and female mice. In order to calculated 50%
      lethal dose (LD50) and approximate lethal dose (LD) , test material was once
      orally administered to male and female ICR mice at dose levels of 2000, 1000,
      500, 250 and 0 (vehicle control) ml/kg (body weight) . The mortality and changes
      on body weight, clinical signs, gross observation, organ weight and
      histopathology of principle organs were monitored 14 days after treatment with
      DHU001. We could not find any mortalities, DHU001 treatment-related clinical
      signs, changes on the body and organ weights, gross and histopathological
      findings. The results obtained in this study suggest that LD50 and approximate LD
      in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both
      female and male mice. 

PMID- 24278507
TI  - Safety Evaluation and Anti-wrinkle Effects of Retinoids on Skin.
AB  - Retinoids have many beneficial effects on dermatological applications. But,
      retinoids cause skin irritation. In this study, the safety of retinoids was
      clarified via both primary skin irritation test in rabbits and sensitization
      study using an integrated model for the differentiation of chemical-induced
      allergic and irritant skin reaction (IMDS) , an alternative method to
      sensitization test. The effects of retinoids on the change of ultraviolet A (UVA)
      -induced matrix metalloproteinase-1 (MMP-1) in human skin fibroblasts and the
      modulation of type-1 pN collagen synthesis in hairless mice were examined to
      clarify the anti-wrinkle effects. All-trans retinol (t-ROL) and its derivative,
      all-trans retinoic acid (t-RA) , showed mild skin irritation but did not induce
      the sensitization. t-ROL and t-RA exerted anti-wrinkle effects by inhibiting the
      UVA-induced MMP-1 in human skin fibroblasts and increasing the type-1 pN collagen
      synthesis in hairless mice. These findings suggest that retinoids do not induce
      the allergy, and show anti-wrinkle effects by decreasing MMP-1 activation and
      increasing collagen synthesis. 

PMID- 24278508
TI  - Reproductive and developmental toxicity of amitraz in sprague-dawley rats.
AB  - The present study was conducted to obtain information on the effects of amitraz
      on reproductive and developmental parameters in rats. The test chemical was
      administered via the drinking water containing 0, 40, 120, and 360 ppm to male
      rats from 2 weeks before mating to the end of 14-day mating period and to females
      from 2 weeks before mating, throughout mating, gestation and up to lactational
      day 4. During the study period, clinical signs, body weights, food intake, organ
      weights, reproductive and littering findings, necropsy findings, sperm
      parameters, and histopathology were examined. At 360 ppm, decreases in the body
      weight gain, food consumption, and the number of live pups and an increase in the
      post-implantation loss were observed. In addition, decreases in the seminal
      vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in
      the food consumption was found transiently in both males and females, but no
      reproductive and developmental toxicity was observed in both sexes. There were no
      signs of either general or reproductive and developmental toxicity in the 40 ppm
      group. Based on these results, it was concluded that the repeated oral
      administration of amitraz to rats resulted in a decrease in the food consumption
      at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the
      number of live pups and an increase in the post-implantation loss at 360 ppm in
      rats. Under these experimental conditions, the no-observed-adverse-effect level
      (NOAEL) of amitraz for general and reproduction/developmental toxicity was
      believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was
      believed to be 40 ppm in rats. 

PMID- 24278509
TI  - Comparison of the short term toxicity of phthalate diesters and monoesters in
      sprague-dawley male rats.
AB  - This study was carried out to investigate the short term toxicity of nine
      phthalate diesters including di-2 (ethylhexyl) phthalate (DEHP) , di (n-butyl)
      phthalate (DBP) , di-n-octyl phthalate (DnOP) , diethyl phthalate (DEP) ,
      butylbenzyl phthalate (BBP) , dimethyl phthalate (DMP) , di-isodecyl phthalate
      (DIDP) , diundecyl phthalate (DUP) , and di-isononyl phthalate (DINP) and five
      phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP) , monobutyl
      phthalate (MBuP) , monobenzyl phthalate (MBeP) , monoethyl phthalate (MEP) ,
      monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats.
      Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day
      (diesters) of phthalate for two weeks. All animals were examined for body and
      organ weights, blood hematology, serum biochemistry, and urine analysis. The body
      weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP,
      MBuP, and PA than that of control. Liver weights were significantly increased in
      the DEHP,DBP, DnOP, DIDP, and MEHP groups as compared to the control group.
      Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP
      treated groups as compared to the control. Significant differences in
      hematological changes were not observed in any treatment groups. Significant
      increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP
      groups. Aspartate aminotransferase (AST) levels were significantly increased in
      the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT)
      levels were significantly increased only in the DEHP and MEHP groups. Serum ALP
      levels were significantly higher in phthalate diester (500 mg/kg/day) -treated
      rats as compared to control. However, the total cholesterol level was
      significantly reduced in the DEHP- and DIDP-treated groups, whereas serum
      triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated
      groups. These results suggest that short term toxicity of phthalate monoesters
      produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.

PMID- 24278511
TI  - Challenges and perspectives of nanoparticle exposure assessment.
AB  - Nanoparticle exposure assessment presents a unique challenge in the field of
      occupational and environmental health. With the commercialization of
      nanotechnology, exposure usually starts from the workplace and then spreads to
      environment and consumer exposure. This report discusses the current trends of
      nanoparticle exposure assessment, including the definition of nanotechnology
      relevant terms, essential physicochemical properties for nanomaterial
      characterization, current international activities related nanomaterial safety,
      and exposure assessment standard development for nanotechnology. Further this
      report describes challenges of nanoparticle exposure assessment such as
      background measurement, metrics of nanoparticle exposure assessment and personal
      sampling. 

PMID- 24278512
TI  - Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice.
AB  - Halogenated organic compounds, such as 1-bromobutane (1-BB) , have been used as
      cleaning agents, agents for chemical syntheses or extraction solvents in
      workplace. In the present study, immunotoxic effects of 1-BB and its conjugation
      with glutathione (GSH) were investigated in female BALB/c mice. Animals were
      treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose
      response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for
      time course. S-Butyl GSH was identified in spleen by liquid chromatography
      electrospray ionization tandem mass spectrometry. Splenic GSH levels were
      significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were
      detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed
      the antibody response to a T-dependent antigen and the production of splenic
      intracellular interlukin-2 in response to Con A. Our present results suggest that
      1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due
      to the formation of GSH conjugates in mice. The present results would be useful
      to understand molecular toxic mechanism of low molecular weight haloalkanes and
      to develop biological markers for exposure to haloalkanes. 

PMID- 24278510
TI  - Modulation of MnSOD in Cancer:Epidemiological and Experimental Evidence.
AB  - Since it was first observed in late 1970s that human cancers often had decreased
      manganese superoxide dismutase (MnSOD) protein expression and activity, extensive
      studies have been conducted to verify the association between MnSOD and cancer.
      Significance of MnSOD as a primary mitochondrial antioxidant enzyme is
      unquestionable; results from in vitro, in vivo and epidemiological studies are in
      harmony. On the contrary, studies regarding roles of MnSOD in cancer often report
      conflicting results. Although putative mechanisms have been proposed to explain
      how MnSOD regulates cellular proliferation, these mechanisms are not capitulated
      in epidemiological studies. This review discusses most recent epidemiological and
      experimental studies that examined the association between MnSOD and cancer, and
      describes emerging hypotheses of MnSOD as a mitochondrial redox regulatory enzyme
      and of how altered mitochondrial redox may affect physiology of normal as well as
      cancer cells. 

PMID- 24278513
TI  - Berberine inhibited radioresistant effects and enhanced anti-tumor effects in the
      irradiated-human prostate cancer cells.
AB  - The purpose of this study was to elucidate the mechanism underlying enhanced
      radiosensitivity to (60)Co gamma-irradiation in human prostate PC-3 cells
      pretreated with berberine. The cytotoxic effect of the combination of berberine
      and irradiation was superior to that of berberine or irradiation alone. Cell
      death and Apoptosis increased significantly with the combination of berberine and
      irradiation. Additionally, ROS generation was elevated by berberine with or
      without irradiation. The antioxidant NAC inhibited berberine and radiation
      induced cell death. Bax, caspase-3, p53, p38, and JNK activation increased, but
      activation of Bcl-2, ERK, and HO-1 decreased with berberine treatment with or
      without irradiation. Berberine inhibited the anti-apoptotic signal pathway
      involving the activation of the HO-1/NF-kappaB-mediated survival pathway, which
      prevents radiation-induced cell death. Our data demonstrate that berberine
      inhibited the radioresistant effects and enhanced the radiosensitivity effects in
      human prostate cancer cells via the MAPK/caspase-3 and ROS pathways. 

PMID- 24278514
TI  - Antifungal Effect of Brachyglottis repanda Ethanol Extract.
AB  - The crude ethanol extract of B. repanda showed the cytotoxic activity against
      Polio virus (25% activity at 150 MUg/disk) and the minor cytotoxic activity
      against BSC cells (African green monkey kidney) . However, the crude ethanol
      extract of B. repanda was non-toxic to murine leukaemia cells CCL 46 P388D1
      (IC50, > 62,500 ng/ml) . Cytotoxic and antifungal activities were strongly shown
      by Fr. 64-3 which was eluted with 90% CH3CN/H2O, 100% CH3CN, and 50% CH3CN/H2O
      (SM 2 at 150 MUg/disk) . The fraction 64-3 also showed the most cytotoxic
      activity against murine leukaemia cells (128 mg, IC50 10,051 ng/ml at 75
      MUg/disk) . These results suggest that this fraction has a potent antifungal
      activity against the dermatophytic fungus Trichophyton mentagrophytes ATCC 28185.

PMID- 24278515
TI  - Effect of DHU001, a Polyherbal Formula, on Dinitrofluorobenzene-induced Contact
      Dermatitis (Type I allergy).
AB  - The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous
      extracts for various respiratory disorders were evaluated on 2,4
      dinitrofluorobenzene (DNFB) -induced contact dermatitis, type I allergic model.
      Contact dermatitis was induced by sensitization with dinitrophenyl-derivatized
      ovalbumin (DNP-OVA) and DNFB challenge as antigen. Two different dosages of
      DHU001 (300 and 150 mg/kg) were orally administered to DNP-OVA sensitization mice
      once a day for 7 days with reference material, dexamethasone (15 mg/kg,
      intraperitoneal treatment) . End of 7 days oral administration of DHU001 extracts
      or intraperitoneal treatment of dexamethasone, the changes on the edematous
      changes and scratching behavior were measured. Immediate after DNFB challenge on
      ear or paw of DNP-OVA sensitized mice, increases of ear and paw thicknesses and
      weights were detected with anterior ear skin (dermis to epidermis) thickness and
      paw scratching behavior increases. However, these contact dermatitis signs
      induced by DNFB treatment were reduced by treatment of the both different dosages
      of DHU001 and dexamethasone, respectively. The results obtained in this study
      suggest that oral treatment of DHU001 extracts also has relatively favorable
      effects on contact dermatitis. 

PMID- 24278516
TI  - Time-dependent Changes of Cadmium and Metallothionein after Short-term Exposure
      to Cadmium in Rats.
AB  - The time-dependent changes in cadmium (Cd) concentration were studied in Female
      Sprague-Dawley (SD) rats during and after Cd exposure via drinking water (10 and
      50 ppm) for 30 days. The cadmium concentration in muscle, liver, kidney, blood
      plasma, and urine, and the metallothionein concentration in blood plasma were
      determined every 10 days during exposure and every 7 days after exposure for 3
      weeks. The muscle Cd concentration did not change during, and neither after,
      exposure. The liver Cd concentration increased from 1.4 to 3.3 (at 10 ppm) and
      from 6.1 to 10.1 folds (at 50 ppm) during exposure and remained higher than those
      of controls in both groups even during post-exposure period. The kidney Cd
      concentrations were 2.3 to 5.1 (at 10 ppm) and 4.9-14.0 folds (at 50 ppm) higher
      than those of controls during exposure and also remained elevated during the post
      exposure period. Plasma Cd concentrations were not significantly different from
      those of controls in both groups. Urine Cd concentrations were more than 2 folds
      (at 10 ppm) and 6.5 to 12.6 folds (at 50 ppm) higher than those of controls but
      rapidly decreased over the 7 days of withdrawal. Blood plasma metallothionein
      concentrations were more than 2.4 folds (at 10 ppm) and 3.1 to 7.4 folds (at 50
      ppm) , and they remained elevated till 7 days (10 ppm) and 14 days (at 50 ppm)
      after exposure. Our data support that Cd in urine could be a useful biomarker
      during Cd exposure period and metallothionein in blood plasma could be as a
      supportive biological marker for during and post Cd exposure. 

PMID- 24278518
TI  - Determination of Trichlorfon Pesticide Residues in Milk via Gas Chromatography
      with MU-Electron Capture Detection and GC-MS.
AB  - The pesticide trichlorfon is readily degraded under experimental conditions to
      dichlorvos. A method has therefore been developed by which residues of
      trichlorfon in milk are determined as dichlorvos, using gas chromatography with
      MU-electron capture detection. The identification of dichlorvos was confirmed by
      mass spectrometry. Milk was extracted with acetonitrile followed by
      centrifugation, freezing lipid filtration, and partitioning into dichloromethane.
      The residue after partitioning of dichloromethane was dissolved in ethyl acetate
      for gas chromatography. Recovery concentration was determined at 0.5, 1.0, and
      2.0 of times the maximum permitted residue limits (MRLs) for trichlorfon in milk.
      The average recoveries (n = 6) ranged from 92.4 to 103.6%. The repeatability of
      the measurements was expressed as relative standard deviations (RSDs) ranging
      from 3.6%, to 6.7%. Limit of detection (LOD) and limit of quantification (LOQ)
      were 3.7 and 11.1 MUg/l, respectively. The accuracy and precision (expressed as
      RSD) were estimated at concentrations from 25 to 250 MUg/l. The intra- and inter
      day accuracy (n = 6) ranged from 89.2%to 91% and 91.3% to 96.3%, respectively.
      The intra- and inter-day precisions were lower than 8%. The developed method was
      applied to determine trichlorfon in real samples collected from the seven major
      cities in the Republic of Korea. No residual trichlorfon was detected in any
      samples. 

PMID- 24278517
TI  - Genome-wide transcriptional response during the development of bleomycin-induced
      pulmonary fibrosis in sprague-dawley rats.
AB  - Pulmonary fibrosis is a common consequence of many lung diseases and a leading
      cause of morbidity and mortality. The molecular mechanisms underlying the
      development of pulmonary fibrosis remain poorly understood. One model used
      successfully to study pulmonary fibrosis over the past few decades is the
      bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes
      associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin
      induced rat model for pulmonary fibrosis. To confirm fibrosis development,
      several analyses were performed, including cellular evaluations using
      bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and
      histopathological examinations. Common aspects of pulmonary fibrosis such as
      prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and
      deposition of extracellular matrix and connective tissue elements were observed.
      Global gene expression analysis revealed significantly altered expression of
      genes (>= 1.5-fold, p < 0.05.) in a time-dependent manner during the development
      of pulmonary fibrosis. Our results are consistent with previous results of well
      documented gene expression. Interestingly, the expression of triggering receptor
      expressed on myeloid cells 2 (Trem2) , secreted phosphoprotein 1 (Spp1) , and
      several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the
      lung after bleomycin treatment, despite little evidence that they are involved in
      pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic
      mechanisms and contribute to the identification of candidate biomarkers of
      fibrotic disease development. 

PMID- 24278519
TI  - A study on characteristics of atmospheric heavy metals in subway station.
AB  - In this study, we investigated the atmospheric heavy metal concentrations in the
      particulate matter inside the subway stations of Seoul. In particular, we
      examined the correlation between the heavy metals and studied the effect of the
      heavy metals on cell proliferation. In six selected subway stations in Seoul,
      particulate matter was captured at the platforms and 11 types of heavy metals
      were analyzed. The results showed that the mean concentration of iron was the
      highest out of the heavy metals in particulate matter, followed by copper,
      potassium, calcium, zinc, nickel, sodium, manganese, magnesium, chromium and
      cadmium in that order. The correlation analysis showed that the correlations
      between the heavy metals was highest in the following order: (Cu vs Zn) , (Ca vs
      Na) , (Ca vs Mn) , (Ni vs Cr) , (Na vs Mn) , (Cr vs Cd) , (Zn vs Cd) , (Cu vs Cd)
      , (Ni vs Cd) , (Cu vs Ni) , (K vs Zn) , (Cu vs K) , (Cu vs Cr) , (K vs Cd) , (Zn
      vs Cr) , (K vs Ni) , (Zn vs Ni) , (K vs Cr) , and (Fe vs Cu) . The correlation
      coefficient between zinc and copper was 0.937, indicating the highest
      correlation. Copper, zinc, nickel, chromium and cadmium, which are generated from
      artificial sources in general, showed correlations with many of the other metals
      and the correlation coefficients were also relatively high. The effect of the
      heavy metals on cell proliferation was also investigated in this study. Cultured
      cell was exposed to 10 mg/l or 100 mg/l of iron, copper, calcium, zinc, nickel,
      manganese, magnesium, chromium and cadmium for 24 hours. The cell proliferation
      in all the heavy metal-treated groups was not inhibited at 10 mg/l of the heavy
      metal concentration. The only exception to this was with the cadmium-treated
      group which showed a strong cell proliferation inhibition. This study provides
      the fundamental data for the understanding of simultaneous heavy metal exposure
      tendency at the time of particulate matter exposure in subway stations and the
      identification of heavy metal sources. Moreover, this study can be used as the
      fundamental data for the cell toxicity study of the subway-oriented heavy metal
      containing particulate matter. 

PMID- 24278521
TI  - Bioactivation of Aromatic Amines by Human CYP2W1, An Orphan Cytochrome P450
      Enzyme.
AB  - The human genome contains approximately 13 orphan cytochrome P450 (P450, CYP)
      genes, of which the apparent function or substrate has not been identified.
      However, they seem to possess their own biological relevance in some tissues or
      developmental stages. Here, we characterized the heterologously expressed CYP2W1,
      an orphan P450 enzyme. The recombinant CYP2W1 protein containing a 6 * (His) -tag
      at Nterminus has been expressed in Escherichia coli and purified. Expression
      level of CYP2W1 holoenzyme was around 500 nmol P450 holoenzyme per liter culture
      medium. The reduced CO difference spectrum of CYP2W1 showed a maximum absorption
      at 449 nm. CYP2W1 indicated the significant induction to bioactivate Trp-P-1,
      MeIQ, and IQ in E. coli DJ701 tester strain. However, the bioactivation of
      B[alpha]P, and NNK by CYP2W1 was relatively low. The model structure of CYP2W1
      suggested the characteristic P450 folds with the lengths and orientations of the
      individual secondary elements. The F-G loop is situated on the distal side of
      heme to accommodate the flexibility of active site of CYP2W1. These studies can
      provide useful information for the finding of its biological roles and structure
      function relationships of an orphan CYP2W1 enzyme. 

PMID- 24278520
TI  - Use of antioxidants to prevent cyclosporine a toxicity.
AB  - Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in
      transplant surgery and the treatment of several autoimmune diseases. However,
      major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity
      and cardiovascular diseases have substantially limited its usage. Although
      molecular mechanisms underlying these adverse effects are not clearly understood,
      there is some evidence that suggests involvement of reactive oxygen species (ROS)
      . In parallel, protective effects of various antioxidants have been demonstrated
      by many research groups. Extensive studies of CsA-induced nephrotoxcity have
      confirmed that the antioxidants can restore the damaged function and structure of
      kidney. Subsequently, there have appeared numerous reports to demonstrate the
      positive antioxidant effects on liver and other organ damages by CsA. It may be
      timely to review the ideas to envisage the relationship between ROS and the CsA
      induced toxicity. This review is comprised of a brief description of the
      immunosuppressive action and the secondary effects of CsA, and a synopsis of
      reports regarding the antioxidant treatments against the ROS-linked CsA toxicity.
      A plethora of recent reports suggest that antioxidants can help reduce many CsA's
      adverse effects and therefore might help develop more effective CsA treatment
      regimens. 

PMID- 24278522
TI  - Promotion of cAMP responsive element-binding protein activity ameliorates
      radiation-induced suppression of hippocampal neurogenesis in adult mice.
AB  - This study was performed to examine whether elevated activity of cAMP responsive
      element-binding protein (CREB) attenuates the detrimental effects of acute gamma
      (gamma) -irradiation on hippocampal neurogenesis and related functions. C57BL/6
      male mice were treated with rolipram (1.25 mg/kg, i.p., twice a day for 5
      consecutive days) to activate the cAMP/CREB pathway against cranial irradiation
      (2 Gy) , and were euthanized at 24 h post-irradiation. Exposure to gamma-rays
      decreased both CREB phosphorylation and immunohistochemical markers for
      neurogenesis, including Ki-67 and doublecortin (DCX) , in the hippocampal dentate
      gyrus (DG) . However, the rolipram treatment protected from gamma-irradiation
      induced decreases of CREB phosphorylation, and Ki-67 and DCX immunoreactivity in
      the hippocampal DG. In an object recognition memory test, mice trained 24 h after
      acute gamma-irradiation (2 Gy) showed significant memory impairment, which was
      attenuated by rolipram treatment. The results suggest that activation of CREB
      signaling ameliorates the detrimental effects of acute gamma-irradiation on
      hippocampal neurogenesis and related functions in adult mice. 

PMID- 24278523
TI  - Fatty Acid Composition of Adipose Tissues in Obese Mice and SD Rats Fed with
      Isaria sinclairii Powder.
AB  - Isaria sinclairii (Cicada Dongchunghacho) was studied as a potential crude
      natural food in powdered form. The role of tissue fatty acids in relation to the
      anti-obesity effects of I. sinclairii (IS) was examined by feeding the powder to
      SD rats ad libitum at 0, 1.25, 2.5, 5 and 10% (calculated about 8 g/kg) of the
      feed for a period of 3 months and 6 months. The fatty acid composition profile as
      indicated GC-MS, showed significantly slight dose-dependent increases in the
      levels of unsaturated fatty acids, particularly, arachidonic acid (C20: 4n6) ,
      oleic acid, linoleic acid, eicosadienoic acid, eicosapentaenoic acid (EPA) (C20:
      5) concentration in the the ad libitum IS-fed groups compared to the control
      group in SD abdominal fat over 6 month period. Over viewing of the SD and Ob mice
      treated Isaria sinclairii powder; there were increases in the single (mono)
      unsaturated fatty acids ratio but decreases in polyunsaturated fatty acid. In IS
      fed groups in proportion to the treatment period, this Dongchunghacho also
      induced an increase in the level of same result of unsaturated fatty acid in
      C57BL/6 obese (ob/ob) mice over a 6-month period treatment compared to those
      given 10% dry mulberry leaf powder (ML) or silkworm powder mixed with the
      standard diet. 

PMID- 24278524
TI  - Inhibitory Effect of 1-O-Hexyl-2,3,5-Trimethylhydroquinone on Dimethylnitrosamine
      induced Liver Fibrosis in Male SD Rats.
AB  - Hepatic fibrosis represents the main complication of most chronic liver disorders
      and, regardless of its etiology, is characterized by excessive deposition of
      extracellular matrix components. In this study, we examined that 1-O-Hexyl-2,3,5
      Trimethylhydroquinone (HTHQ) , a potent anti-oxidative agent, could prevent
      experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in male SD
      rats. Except for vehicle control group, other groups were induced hepatic
      fibrosis by intraperitoneal injection with DMN (10 mg/ml/kg) on 3 consecutive
      days weekly for 4 weeks. During the same 4 weeks, control and DMN groups were
      given vehicle and HTHQ 50, 100 and 200 groups were orally administered HTHQ (50,
      100, 200 mg/kg respectively) . In HTHQ 100 and 200 groups, relative liver weight
      and serum chemistry level improved significantly. HTHQ reduced hydroxyproline (p
      < 0.05) and malondialdehyde (p < 0.05) level in the liver. Histopathological
      examination of H&E, Masson's trichrome stain showed the reduced fibrotic septa in
      HTHQ 100 and 200 groups. HTHQ administration showed reduced mRNA level of PDGF
      (Plateletderived growth factor) , alpha-SMA (alpha-smooth muscle actin) and TGF
      beta (transforming growth factor-beta) than DMN-induced hepetic fibrosis animals
      in the liver tissue. In this study, we showed that HTHQ improves against DMN
      induced liver fibrosis in male SD rats. 

PMID- 24278525
TI  - Standardization of bronchoalveolar lavage method based on suction frequency
      number and lavage fraction number using rats.
AB  - Bronchoalveolar lavage (BAL) is a useful tool in researches and in clinical
      medicine of lung diseases because the BAL fluid contains biochemical and
      cytological indicators of the cellular response to infection, drugs, or
      toxicants. However, the variability among laboratories regarding the technique
      and the processing of the BAL material limits clinical research. The aim of this
      study was to determine the suction frequency and lavage fraction number necessary
      to reduce the variability in lavage using male Sprague-Dawley rats. We compared
      the total cell number and protein level of each lavage fraction and concluded
      that more cells and protein can be obtained by repetitive lavage with a suction
      frequency of 2 or 3 than by lavage with a single suction. On the basis of total
      cell recovery, approximately 70% of cells were obtained from fractions 1~3. The
      first lavage fraction should be used for evaluation of protein concentration
      because fractions 2~5 of lavage fluid were diluted in manifolds. These
      observations were confirmed in bleomycin-induced inflamed lungs of rats. We
      further compared the BAL data from the whole lobes with data from the right lobes
      and concluded that BAL data of the right lobes represented data of the whole
      lobes. However, this conclusion can only be applied to general lung diseases. At
      the end, this study provides an insight into the technical or analytical problems
      of lavage study in vivo. 

PMID- 24278526
TI  - Evaluation of embryotoxic potential of olaquindox and vitamin a in micromass
      culture and in rats.
AB  - Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day
      old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A.
      Cytotoxicity and inhibition on differentiation were measured in each cell. Three
      doses of olaquindox (4, 21 and 100 mgkg) , and 0.2 and 75 mg/kg of vitamin A were
      administered to pregnant rat for 11 days from 6(th) to 16(th) of pregnancy. IC50
      values of olaquindox for proliferation and differentiation in CNS cell were 22.74
      and 28.32 MUg/ml and 79.34 and 23.29 MUg/ml in LB cell and those values of
      vitamin A were 8.13 and 5.94 MUg/ml in CNS cell and 0.81 and 0.05 MUg/ml in LB
      cell, respectively. Mean body weights of pregnant rats were decreased at high
      dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea,
      and number of implantation were not changed. Resorption and dead fetus were
      increased at high dose of olaquindox, and relative ovary weight, the number of
      corpus lutea and implantation, and sex ratio of male to female were not
      significantly changed in all dose of olaquindox. Mean fetal and placenta weights
      were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out
      of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed
      visceral anomalies at high group. The ossification of sternebrae and metacarpals
      were significantly (p < 0.01) increased by low and middle dose of olaquindox but
      it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats
      treated with vitamin A, the resorption and dead fetus were increased by high
      dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but
      significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52
      showed external anomaly; bent tail (1) , cranioarchschisis (14) , exencephaly
      (14) , dome shaped head (22) , anophthalmia (15) , brcahynathia (10) and others
      (19) . Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate
      (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out
      of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone
      (21/61) , defect of palatine bone (52/61) and others (50/61) . In summary, we
      support that vitamin A is strong teratogen based on our micromass and in vivo
      data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS
      cell. We provide the in vivo evidence that a high dose of olaquindox could have
      weak embryotoxic potential in rats. 

PMID- 24278527
TI  - Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in
      Mice.
AB  - Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary
      fibrosis as a side effect. However, few investigations have focused on the dose
      response effects of bleomycin on pulmonary fibrosis. Therefore, in the present
      study, we investigated the effects of different doses of bleomycin in male mice.
      ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in
      bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The
      animals were sacrificed at 7 and 24 days postinstillation. The severity of
      pulmonary fibrosis was evaluated according to inflammatory cell count and lactate
      dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF) , and
      lung tissues were histologically evaluated after hematoxylin and eosin (H&E) ,
      and Masson's trichrome staining. BT groups exhibited changed cellular profiles in
      BAL fluid compared to the VC group, which had an increased number of total cells,
      neutrophils, and lymphocytes and a modest increase in the number of macrophages
      at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose
      dependent increase in LDH levels and inflammatory cell counts. However, at 24
      days after treatment, collagen deposition, interstitial thickening, and
      granulomatous lesions were observed in the alveolar spaces in addition to a
      decrease in inflammatory cells. These results indicate that pulmonary fibrosis
      induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg.
      These data will be utilized in experimental animal models and as basic data to
      evaluate therapeutic candidates through non-invasive monitoring using the
      pulmonary fibrosis mouse model established in this study. 

PMID- 24278528
TI  - General Pharmacology of Artesunate, a Commonly used Antimalarial Drug:Effects on
      Central Nervous, Cardiovascular, and Respiratory System.
AB  - Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a
      treatment for malaria. Its effects on the central nervous system, general
      behavior, and cardiovascular, respiratory, and other organ systems were studied
      using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to
      mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200,
      and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules
      at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in
      general pharmacological studies, including general behavior, motor coordination,
      body temperature, analgesia, convulsion modulation, blood pressure, heart rate
      (HR) , and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs;
      and gut motility or direct effects on isolated guinea pig ileum, contractile
      responses, and renal function. On the other hand, artesunate decreased the HR and
      coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes
      was small and they were not confirmed in in vivo studies in the dog. Artesunate
      increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate
      induced dose-related decreases in the volume of gastric secretions and the total
      acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg.
      However, all of these changes were observed at doses much greater than clinical
      therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial) . Thus, it
      can be concluded that artesunate is safe at clinical therapeutic doses. 

PMID- 24278529
TI  - Assay of In Vivo Chromium with a Hollow-fiber Dialysis Sensor.
AB  - The analytical in vivo chromium ion was searched for using a voltammetric hollow
      fiber dialysis sensor via square wave stripping voltammetry (SW) , cyclic
      voltammetry (CV) , and chronoamperometry. Under optimum parameters, the
      analytical results indicated linear working ranges of 50~400 mg/l CV and 10~80
      MUg/l SW within a 30-sec accumulation time. The analytical detection limit (S/N)
      was 6.0 MUg/l. The developed method can be applied to in vivo tissues and in ex
      vivo toxicity assay, as well as to other materials that require chromium
      analysis. 

PMID- 24278530
TI  - Toxicological mechanism of endocrine disrupting chemicals:is estrogen receptor
      involved?
AB  - Endocrine disrupting chemicals (EDCs) have been shown to interfere with
      physiological systems, i.e., adversely affecting hormone balance (endocrine
      system) , or disrupting normal function, in the female and male reproductive
      organs. Although endocrine disruption is a global concern for human health, its
      impact and significance and the screening strategy for detecting these synthetic
      or man-made chemicals are not clearly understood in female and male reproductive
      functions. Thus, in this review, we summarize the interference of environmental
      EDCs on reproductive development and function, and toxicological mechanism (s) of
      EDCs in in vitro and in vivo models of male and female reproductive system. In
      addition, this review highlights the effect of exposure to multiple EDCs on
      reproductive functions, and brings attention to their toxicological mechanism (s)
      through estrogen receptors. 

PMID- 24278532
TI  - Research trends of ecotoxicity of nanoparticles in soil environment.
AB  - We are consistently being exposed to nanomaterials in direct and/or indirect
      route as they are used in almost all the sectors in our life. Nations across the
      worlds are now trying to put global regulation policy on nanomaterials.
      Sometimes, they are reported to be more toxic than the corresponding ion and
      micromaterials. Therefore, safety research of nanoparticles has huge implications
      on a national economics. In this study, we evaluated and analyzed the research
      trend of ecotoxicity of nanoparticles in soil environment. Test species include
      terrestrial plants, earthworms, and soil nematode. Soil enzyme activities were
      also discussed. We found that the results of nanotoxicity studies were affected
      by many factors such as physicochemical properties, size, dispersion method and
      test medium of nanoparticle, which should be considered when conducting toxicity
      researches. In particular, more researches on the effect of physico chemical
      properties and fate of nanoparticles on toxicity effect should be conducted
      consistently. 

PMID- 24278531
TI  - Epithelial-mesenchymal Transition and Cell Invasion.
AB  - Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial
      cells acquire the characteristics of invasive mesenchymal cells. EMT has been
      implicated in cancer progression and metastasis as well as the formation of many
      tissues and organs during development. Epithelial cells undergoing EMT lose cell
      cell adhesion structures and polarity, and rearrange their cytoskeletons. Several
      oncogenic pathways such as transforming growth factor (TGF) -beta, Wnt, and Notch
      signaling pathways, have been shown to induce EMT. These pathways have activated
      transcription factors including Snail, Slug, and the ZEB family which work as
      transcriptional repressors of E-cadherin, thereby making epithelial cells motile
      and resistant to apoptosis. Mounting evidence shows that EMT is associated with
      cell invasion and tumor progression.In this review, we summarize the
      characteristic features of EMT, pathways leading to EMT, and the role of EMT in
      cell invasion. Three topics are addressed in this review: (1) Definition of EMT,
      (2) Signaling pathways leading to EMT, (3) Role of EMT in cell invasion.
      Understanding the role of EMT in cell invasion will provide valuable information
      for establishing strategies to develop anti-metastatic therapeutics which
      modulate malignant cellular processes mediated by EMT. 

PMID- 24278533
TI  - Inhalation toxicity of particulate matters doped with arsenic induced
      genotoxicity and altered akt signaling pathway in lungs of mice.
AB  - In the workplace, the arsenic is used in the semiconductor production and the
      manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers
      may be exposed to airborne arsenic during its use in manufacturing. The purpose
      of this study was to evaluate the potential toxicity of particulate matters (PMs)
      doped with arsenic (PMs-Arsenic) using a rodent model and to compare the
      genotoxicity in various concentrations and to examine the role of PMs-Arsenic in
      the induction of signaling pathway in the lung. Mice were exposed to PMs 124.4 +/
      24.5 MUg/m(3) (low concentration) , 220.2 +/- 34.5 MUg/m(3) (middle
      concentration) , 426.4 +/- 40.3 MUg/m(3) (high concentration) doped with arsenic
      1.4 MUg/m(3) (Low concentration) ,2.5 MUg/m(3) (middle concentration) , 5.7
      MUg/m(3) (high concentration) for 4 wks (6 h/d, 5 d/wk) , respectively in the
      whole-body inhalation exposure chambers. To determine the level of genotoxicity,
      Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital
      micronucleus (SMN) assay were performed. Then, signal pathway in the lung was
      analyzed. In the genotoxicity experiments, the increases of aberrant cells were
      concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus
      frequency at high concentration. The inhalation of PMs-Arsenic increased an
      expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated
      mammalian target of rapamycin (p-mTOR) at high concentration group. Taken
      together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling
      pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful
      risk assessment in the workplace. 

PMID- 24278534
TI  - Induction of Inflammatory Responses by Carbon Fullerene (C60) in Cultured
      RAW264.7 Cells and in Intraperitoneally Injected Mice.
AB  - As the use of carbon fullerene increases in the chemical industry, the concern
      over its biological and toxicological effects is also increasing. In this study,
      the suspension of carbon fullerene (C60) in phosphate buffered saline was
      prepared and toxicity was investigated using cultured RAW 264.7 and in
      intraperitoneally injected mice, respectively. The average size of carbon
      fullerene in the suspension was 53.7 +/- 26.5 nm when determined by particle size
      analyzer. Cell viability was significantly decreased by the exposure of carbon
      fullerene (0.25~2.00 MUg/ml) for 96 hrs in the cultured RAW 264.7 cells.
      Intracellular reduced glutathione (GSH) level was also decreased compared to the
      level of the non-treated control group during the exposure period, while the
      level of nitric oxide was increased. When mice were intraperitoneally injected
      with carbon fullerene, serum cytokine levels of IL-1 and IL-6 were increased with
      the increased expression of inflammatory genes in peritoneal macrophage and T
      cell distribution in blood lymphocytes.The results suggested inflammatory
      responses were induced by carbon fullerene. 

PMID- 24278535
TI  - Placenta transfer and toxicokinetics of valproic Acid in pregnant cynomolgus
      monkeys.
AB  - Placenta transfer study in non-human primate (NHP) is one of the crucial
      components in the assessment of developmental toxicity because of the similarity
      between NHP and humans. To establish the method to determine placenta transfer in
      non-human primate, toxicokinetics of valproic acid (VPA) , a drug used to treat
      epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After
      mating, pregnancy-proven females were daily administered with VPA at dose levels
      of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from
      gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA,
      in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in
      placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS.
      Following single oral administration of VPA to pregnant monkeys, concentrations
      of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment
      groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the
      monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated
      administration of VPA to the monkeys, VPA was detected in amniotic fluid,
      placenta and fetus from all treatment groups, demonstrating that VPA was
      transferred via placenta and the fetus was exposed to VPA, and the exposures were
      increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and
      fetus were below the limit of quantification, but small amount of 4-ene-VPA was
      detected in placenta. In conclusion,pregnant monkeys were exposed to VPA and 4
      ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg
      during the organogenesis period. VPA was transferred via placenta and the fetus
      was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was
      not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was
      detected in placenta. These results demonstrated that proper procedures to
      investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy
      via examining gestational sac with ultrasonography, collection of amniotic fluid,
      placenta and fetus after Caesarean section followed by adequate bioanalysis and
      toxicokinetic analysis, were established in this study using cynomolugus monkeys.

PMID- 24278536
TI  - Establishment of the korean tolerable daily intake of bisphenol a based on risk
      assessments by an expert committee.
AB  - Recently, reproductive and neurobehavioral effects of bisphenol A (BPA) have been
      documented, and thus a review was requested for BPA management direction by the
      government. Therefore, this study was performed to establish a Korean tolerable
      daily intake (TDI) for BPA. An expert committee, consisting of specialists in
      fields such as toxicology, medicine, pharmacology, and statistics, was asked to
      evaluate BPA health based guidance values (HbGVs) . Although many toxicological
      studies were reviewed to select a point of departure (POD) for TDI, rat and mouse
      reproductive studies by Tyl et al. (2002, 2006) , which were performed according
      to GLP standards and OECD guidelines, were selected. This POD was the lowest
      value determined from the most sensitive toxicological test. The POD, a NOAEL of
      5 mg/kg bw/day, was selected based on its systemic toxicity as critical effects.
      An uncertainty factor of 100 including interspecies and intraspecies differences
      was applied to calculate the TDI. According to the evaluation results, a TDI of
      BPA for Korean was suggested at 0.05 mg/kg bw/day. In addition, the BPA exposure
      level based on food consumption by the Korean population was estimated as 1.509
      MUg/kg bw/day, and the HI was evaluated at 0.03 when the TDI of 0.05 mg/kg bw/day
      was applied. This HI value of 0.03 indicated that hazardous effects would not be
      expected from BPA oral exposures. Although highly uncertain, further studies on
      low dose neurobehavioral effects of BPA should be performed. In addition, it is
      recommended that the 'as low as reasonably achievable' (ALARA) principle be
      applied for BPA exposure from food packaging materials in newborn infants and
      children. 

PMID- 24278537
TI  - LC50 Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in
      Rats.
AB  - tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in
      architectural coatings and industrial solvents. It has recently been exempted
      from the definition of a volatile organic compound (VOC) by the Air Resources
      Board (ARB) . Since the use of TBAc as a substitute for other VOCs has increased,
      thus its potential risk in humans has also increased. However, its inhalation
      toxicity data in the literature are very limited. Hence, inhalation exposure to
      TBAc was carried out to investigate its toxic effects in this study. Adult male
      rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation
      exposure chamber (low dose, 2370 mg/m(3) (500 ppm) ; high dose, 9482 mg/m(3)
      (2000 ppm) ) . Shamtreated control rats were exposed to clean air in the
      inhalation chamber for the same period. The animals were killed at 2, 7, and 15
      days after exposure. At each time point, body weight measurement, bronchoalveolar
      lavage fluid (BALF) analysis, histopathological examination, and biochemical
      assay were performed. No treatment-related abnormal effects were observed in any
      group according to time course. Based on those findings, the median lethal
      concentration (LC50) of TBAc was over 9482 mg/m(3) in this study. According to
      the MSDS, the 4 h LC50 for TBAc for rats is over 2230 mg/m(3). We suggested that
      this value is changed and these findings may be applied in the risk assessment of
      TBAc which could be beneficial in a sub-acute study. 

PMID- 24278538
TI  - Risk assessment of growth hormones and antimicrobial residues in meat.
AB  - Growth promoters including hormonal substances and antibiotics are used legally
      and illegally in food producing animals for the growth promotion of livestock
      animals. Hormonal substances still under debate in terms of their human health
      impacts are estradiol-17beta, progesterone, testosterone, zeranol, trenbolone,
      and melengestrol acetate (MGA) . Many of the risk assessment results of natural
      steroid hormones have presented negligible impacts when they are used under good
      veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have
      been established for food safety along with the approval of animal treatment.
      Small amounts of antibiotics added to feedstuff present growth promotion effects
      via the prevention of infectious diseases at doses lower than therapeutic dose.
      The induction of antimicrobial resistant bacteria and the disruption of normal
      human intestinal flora are major concerns in terms of human health impact.
      Regulatory guidance such as ADIs and MRLs fully reflect the impact on human
      gastrointestinal microflora. However, before deciding on any risk management
      options, risk assessments of antimicrobial resistance require large-scale
      evidence regarding the relationship between antimicrobial use in food-producing
      animals and the occurrence of antimicrobial resistance in human pathogens. In
      this article, the risk profiles of hormonal and antibacterial growth promoters
      are provided based on recent toxicity and human exposure information, and
      recommendations for risk management to prevent human health impacts by the use of
      growth promoters are also presented. 

PMID- 24278539
TI  - Toluene induces depression-like behaviors in adult mice.
AB  - It has been clinically reported that toluene causes mental depression in humans.
      However, the detrimental effects of toluene exposure on brain function and the
      relation between features of mental depression and toluene exposure are poorly
      understood. This study evaluated depression-like behaviors in adult C57BL/6 mice
      after administration of toluene, and elucidated the effects of classical
      antidepressants on the depression-like behaviors. For the estimation of
      depression-like behaviors, tail suspension test (TST) and forcedswim test (FST)
      were performed 1, 4 and 16 days after toluene (0~1000 mg/kg bw) treatment. In
      addition, classical antidepressants such as fluoxetine (FLX, 20 mg/kg bw) and
      imipramine (IMI, 40 mg/kg bw) were administered 12 h and 1 h before the tests. In
      the TST and FST, toluene-treated mice exhibited a longer duration of immobility
      than vehicle-treated mice 1 and 4 days after toluene treatment. The depression
      like behaviors were significantly reversed by FLX and IMI. The weight of the
      adrenal gland and the size of adrenocortical cells were significantly higher in
      toluene-treated mice compared to vehicle-treated controls. It is suggested that
      acute toluene exposure of adult mice is sufficiently detrimental to induce
      depression. In addition, this study has established a mouse model for a
      depressive state induced by toluene treatment. 

PMID- 24278540
TI  - Comparison of hydroxyl radical, peroxyl radical, and peroxynitrite scavenging
      capacity of extracts and active components from selected medicinal plants.
AB  - The ability of 80% ethanol extracts from five medicinal plants, Aralia
      continentalis, Paeonia suffruticosa, Magnolia denudata, Anemarrhena
      asphodeloides, and Schizonepeta tenuifolia, to neutralize hydroxyl radical,
      peroxyl radical and peroxynitrite was examined using the total oxyradical
      scavenging capacity (TOSC) assay. Peroxyl radical was generated from thermal
      homolysis of 2,2'-azobis (2-methylpropionamidine) dihydrochloride (ABAP) ;
      hydroxyl radical by an iron-ascorbate Fenton reaction; peroxynitrite by
      spontaneous decomposition of 3-morpholinosydnonimine N-ethylcarbamide (SIN-1) .
      The oxidants generated react with alpha-keto-gamma-methiolbutyric acid (KMBA) to
      yield ethylene, and the TOSC of the substances tested is quantified from their
      ability to inhibit ethylene formation. Extracts from P. suffruticosa, M.
      denudata,and S. tenuifolia were determined to be potent peroxyl radical
      scavenging agents with a specific TOSC (sTOSC) being at least six-fold greater
      than that of glutathione (GSH) . These three plants also showed sTOSCs toward
      peroxynitrite markedly greater than sTOSC of GSH, however, only P. suffruticosa
      revealed a significant hydroxyl radical scavenging capacity. Seven major active
      constituents isolated from P. suffruticosa, quercetin, (+) -catechin, methyl
      gallate, gallic acid, benzoic acid, benzoyl paeoniflorin and paeoniflorin, were
      determined for their antioxidant potential toward peroxynitrite, peroxyl and
      hydroxyl radicals. Quercetin, (+) -catechin, methyl gallate, and gallic acid
      exhibited sTOSCs 40~85 times greater than sTOSC of GSH. These four components
      also showed a peroxynitrite scavenging capacity higher than at least 10-fold of
      GSH. For antioxidant activity against hydroxyl radical, methyl gallate was
      greatest followed by gallic acid and quercetin. Further studies need to be
      conducted to substantiate the significance of scavenging a specific oxidant in
      the prevention of cellular injury and disease states caused by the reactive free
      radical species. 

PMID- 24278541
TI  - Levels of Exhaled Breath Condensate pH and Fractional Exhaled Nitric Oxide in
      Retired Coal Miners.
AB  - Inhaled inorganic dusts, such as coal, can cause inflammation and fibrosis in the
      lungs, known as pneumoconiosis. Diagnosis of pneumoconiosis depends on
      morphological changes by radiological findings and functional change by pulmonary
      function test (PFT) . Unfortunately, current diagnostic findings are limited only
      to lung fibrosis, which is usually irreversibly progressive. Therefore, it is
      important that research on potential and prospective biomarkers for
      pneumoconiosis should be conducted prior to initiation of irreversible
      radiological or functional changes in the lungs. Analytical techniques using
      exhaled breath condensate (EBC) or exhaled gas are non-invasive methods for
      detection of various respiratory diseases. The objective of this study is to
      investigate the relationship between inflammatory biomarkers, such as EBC pH or
      fractional exhaled nitric oxide (FENO) , and pneumoconiosis among 120 retired
      coal miners (41 controls and 79 pneumoconiosis patients) . Levels of EBC pH and
      FENO did not show a statistically significant difference between the
      pneumoconiosis patient group and pneumoconiosis patients with small opacity
      classified by International Labor Organization (ILO) classification. The mean
      concentration of FENO in the low percentage FEV1 (< 80%) was lower than that in
      the high percentage (80% <=) (p = 0.023) . The mean concentration of FENO in
      current smokers was lower than that in non smokers (never or past smokers) (p =
      0.027) . Although there was no statistical significance, the levels of FENO in
      smokers tended to decrease, compared with non smokers, regardless of
      pneumoconiosis. In conclusion, there was no significant relationship between the
      level of EBC pH or FENO and radiological findings or PFT. The effects between
      exhaled biomarkers and pneumoconiosis progression, such as decreasing PFT and
      exacerbation of radiological findings, should be monitored. 

PMID- 24278542
TI  - Lipid peroxidation and its toxicological implications.
AB  - Lipid peroxidation is a free radical oxidation of polyunsaturated fatty acids
      such as linoleic acid or arachidonic acid. This process has been related with
      various pathologies and disease status mainly because of the oxidation products
      formed during the process. The oxidation products include reactive aldehydes such
      as malondialdehyde and 4-hydroxynonenal. These reactive aldehydes can form
      adducts with DNAs and proteins, leading to the alterations in their functions to
      cause various diseases. This review will provide a short summary on the
      implication of lipid peroxidation on cancer, atherosclerosis, and
      neurodegeneration as well as chemical and biochemical mechanisms by which these
      adducts affect the pathological conditions. In addition, select examples will be
      presented where antioxidants were used to counteract oxidative damage caused by
      lipid peroxidation. At the end, isoprostanes are discussed as a gold standard for
      the assessment of oxidative damages. 

PMID- 24278543
TI  - Possible health effects of caffeinated coffee consumption on Alzheimer's disease
      and cardiovascular disease.
AB  - Coffee has been known to have both beneficial and harmful effects upon health.
      Coffee is one of the most widely consumed beverages, worldwide.
      Dementia/Alzheimer's disease (AD) and cardiovascular disease (CVD) are public
      health problems that are rapidly increasing in the aging population. Due to the
      high consumption of coffee, even small effects on an individual's health could
      have a large effect on public health.The aim of this review article is to provide
      an overview of previously published studies of coffee consumption on health.
      Herein, we focus on epidemiological and experimental findings to investigate
      whether coffee-drinking habits, and/or the quantity of coffee consumption, have
      any relationship to CVD, dementia/AD, and other chronic diseases. Although the
      underlying mechanisms are not fully understood, when comparing coffee drinkers
      with non-drinkers, moderate doses of caffeine showed protective effects against
      CVD and AD. We hypothesized that caffeine may be a novel therapy to treat CVD and
      dementia/AD. 

PMID- 24278544
TI  - Anti-inflammatory Activity of Dichloromethane Extract of Auricularia auricula
      judae in RAW264.7 Cells.
AB  - The present study investigated the anti-inflammatory effects of dichloromethane
      extract of Auricularia auricula-judae. Dichloromethane extract of Auricularia
      auricula-judae inhibited Lipopolysaccharide (LPS) -induced nitric oxide (NO)
      production significantly in a dose-dependent manner in the concentration >=10
      MUg/ml (p < 0.05) . Furthermore, RT-PCR results of this study indicated that the
      extract markedly reduced the expressions of inflammatory cytokines (IL-6, TNF
      alpha and IL-1beta) mRNA in LPS-treated murine RAW 264.7 macrophages, which could
      possibly ameliorate the inflammation. Nevertheless, dichloromethane extract of
      Auricularia auricula-judae did not show complete inhibition of IL-6 mRNA
      expression. The inhibition of IL-1beta cytokine at protein level was also
      observed in a dose dependent manner. In conclusion,the current study revealed the
      previously unknown effect of dichloromethane ethyl extract of Auricularia
      auricula-judae inhibitions of the production of NO, IL-6, TNF-alpha and IL-1beta
      in LPS-stimulated macrophages. 

PMID- 24278545
TI  - 1-OH-Pyrene and 3-OH-Phenanthrene in Urine Show Good Relationship with their
      Parent Polycyclic Aromatic Hydrocarbons in Muscle in Dairy Cattle.
AB  - The toxicities of phenanthrene (PH) and pyrene (PY) are less than benzo (a)
      pyrene (BaP) , but both compounds are found in higher concentrations in the air,
      feed, and food. Most PAHs are metabolized to hydroxylated compounds by the
      hepatic cytochrome P450 monooxigenases system. Metabolites are excreted into
      urine and feces. We determined concentrations of PH, PY and BaP in muscle and
      hydroxylated metabolites, 3-OH-PH, 1-OH-PY, and 3-OH-BaP, respectively, in urine
      from dairy cattle (n = 24) . We also evaluated the relationship between parent
      compounds in muscle and their metabolites in urine. Concentrations of PH and PY
      in muscle ranged from 0.7~4.8 ng/g (1.8 +/- 1.7) and 0.4~4.1 ng/g (1.2 +/- 1.2) ,
      respectively. Concentrations of 3-OH-PH and 1-OH-PY in urine ranged from 0.1~5.9
      ng/ml (2.9 +/- 3.7) and 0.5~3.6 ng/ml (1.9 +/- 2.3) , respectively. Correlation
      coefficient for PY concentration in muscle versus 1-OH-PY in urine was 0.657 and
      for PH concentration in muscle versus 3-OH-PH in urine was 0.579.Coefficient
      determination for PY and PH concentrations in muscle was 0.886 and for 1-OH-PY
      and 3-OHPH in urine was 0.834. This study suggests that 1-OH-PY and 3-OH-PH could
      be used as biomarkers for PAHs exposure in dairy cattle. 

PMID- 24278546
TI  - Inhalation exposure to nickel hydroxide nanoparticles induces systemic acute
      phase response in mice.
AB  - It has been proposed that acute phase response can be a mechanism by which
      inhaled particles exert adverse effects on the cardiovascular system. Although
      some of the human acute phase proteins have been widely studied as biomarkers of
      systemic inflammation or cardiovascular diseases, there are only a few studies
      that investigated the role of serum amyloid P (SAP) , a major acute phase protein
      in mice. In this study, we investigated the changes in SAP, following inhalation
      exposure to nickel hydroxide nanoparticles (nano-NH) . We conducted 1) acute (4
      h) exposure to nano-NH at 100, 500, and 1000 MUg/m(3) and 2) sub-acute (4h/d for
      3d) exposure at 1000 MUg/m(3), then measured serum SAP protein levels along with
      hepatic Sap mRNA levels. The results show that inhaled nano-NH can induce
      systemic acute phase response indicated by increased serum SAP levels and hepatic
      Sap mRNA levels. To the best of our knowledge, this is the first study showing
      induction of SAP in response to repeated particle exposure, and the results
      suggest that SAP can be used as a biomarker for systemic inflammation induced by
      inhaled particles. 

PMID- 24278547
TI  - Expression of CYP2A6, CYP2D6 and CYP4A11 Polymorphisms in COS7 Mammalian Cell
      Line.
AB  - The cytochrome P450 (P450, CYP) are the superfamily of heme-containing
      monooxygenase enzymes, found throughout all nature including mammals, plants, and
      microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a
      wide range of endo- and exogenous chemicals. Especially P450s involved in drug
      metabolisms are important for drug efficacy and polymorphisms of P450s in
      individuals reflect differences of drug responses between people. To study the
      functional differences of CYP2A6, CYP2D6, and CYP4A11 variants, we cloned the
      four CYP2A6, three CYP2D6, and three CYP4A11 variants, which were found in Korean
      populations, in mammalian expression vector pcDNA by PCR and examined their
      expressions in COS-7 mammalian cells using immunoblots using P450 specific
      polyclonal antibodies. Three of four CYP2A6, two of three CYP4A11, and two of
      three CYP2D6 variants showed expressions in COS-7 cells but the relative levels
      of expressions are remarkably different in those of each variants. Our findings
      may help to study and explain the differences between functions of CYP variants
      and drug responses in Korean populations. 

PMID- 24278548
TI  - Evaluation of antimicrobial activity of the methanol extracts from 8 traditional
      medicinal plants.
AB  - The methanol extract of 12 medicinal plants were evaluated for its antibacterial
      activity against Gram-positive (5 strains) and Gram-negative bacteria (10
      strains) by assay for minimum inhibitory concentration (MIC) and minimum
      bacterial concentration (MBC) . The antibacterial activity was determined by an
      agar dilution method (according to the guidelines of Clinical and Laboratory
      Standard Institute) . All the compounds (12 extracts) of the 8 medicinal plants
      (leaf or root) were active against both Gram-negative and Gram-positive bacteria.
      Gram-negative showed a more potent action than Gram positive bacteria. The MIC
      concentrations were various ranged from 0.6 MUg/ml to 5000 MUg/ml. The lowest MIC
      (0.6 MUg/ml) and MBC (1.22 MUg/ml) values were obtained with extract on 4 and 3
      of the 15 microorganisms tested, respectively. 

PMID- 24278549
TI  - Antioxidative action of corni fructus aqueous extract on kidneys of diabetic
      mice.
AB  - This study investigated the antioxidative action of Corni Fructus aqueous extract
      on kidneys of diabetic mice. The electron donating abilities of Corni Fructus
      aqueous extract and its antioxidant activities (XO, SOD, CAT, GST, eNOS) in
      kidneys of C57BL/6 or db/db mice were evaluated. For in vivo study, seven week
      old male mice were divided into normal control group (NC, C57BL/6 mice) ,
      diabetic control group (DC, db/db mice) and Corni Fructus (500 mg/kg/day for 8
      weeks) treated diabetic group (DCF, db/db mice) . The electron donating abilities
      of Corni Fructus aqueous extract exhibited 7%, 24.4%, and 42.7% at concentrations
      of 100, 500, and 1000 MUg/ml, respectively. The activity of XO in the DCF group
      was significantly lower than the DC group by 35% (p < 0.05) . The SOD activity
      was significantly higher in the DCF group than the DC group by 26% (p < 0.05) .
      The activities of CAT and GST were lowered in the DCF group than the DC group by
      26% (p < 0.05) and 7.6%, respectively. The mRNA expression of eNOS in kidneys was
      lower in the DCF group than the DC group by 24%. These results indicate that
      Corni Fructus reduced oxidation stress as evidenced by the restoration of the
      enzymatic antioxidative defense system in renal tissues of db/db mice. It is
      suggested that these antioxidative actions of Corni Fructus on renal tissues in
      db/db mice could contribute to its renoprotective effects on diabetic
      nephropathy. 

PMID- 24278550
TI  - Differential gene expression analysis in k562 human leukemia cell line treated
      with benzene.
AB  - Even though exposure to benzene has been linked to a variety of cancers including
      leukemia, the detailed molecular mechanisms relevant to benzene-induced
      carcinogenesis remain to be clearly elucidated. In this study, we evaluated the
      effects of benzene on differential gene expression in a leukemia cell line. The
      K562 leukemia cell line used in this study was cultured for 3 h with 10 mM
      benzene and RNA was extracted. To analyze the gene expression profiles, a 41,000
      human whole genome chip was employed for cDNA microarray analysis. We initially
      identified 6,562 genes whose expression was altered by benzene treatment. Among
      these, 3,395 genes were upregulated and 3,167 genes were downregulated by more
      than 2-fold, respectively. The results of functional classification showed that
      the identified genes were involved in biological pathways including
      transcription, cell proliferation, the cell cycle, and apoptosis. These gene
      expression profiles should provide us with further insights into the molecular
      mechanisms underlying benzene-induced carcinogenesis, including leukemia. 

PMID- 24278551
TI  - Bisphenol-A Concentrations from Leiomyoma Patients by LC/MS.
AB  - The aim of this study is to investigate how many leiomyoma patients are exposed
      to bisphenol-A (BPA) , an endocrine disruptor, and whether the serum
      concentration of BPA is related to leiomyoma growth. Initially, 128 patients were
      divided into one control and three leiomyoma groups (mild, moderate and severe)
      according to the size of the leiomyomas. Serum BPA concentrations were measured
      by liquid chromatography and mass spectrometry (LC/MS) . Nearly two-thirds of
      leiomyoma patients were exposed to BPA and the range of BPA was from non
      detection to 2.603 ng/ml. The mean BPA concentrations in the groups were 1.015 +/
      0.775 ng/ml (control) , 0.774 +/- 0.834 ng/ml (mild) , 1.261 +/- 0.797 ng/ml
      (moderate) and 1.244 +/- 0.860 ng/ml (severe) (p = 0.158) . After recombination
      into two group, Group 1 (control plus mild) vs. Group 2 (moderate plus severe) ,
      higher level was found in Group 2 even with no statistical significance (p =
      0.06) . In conclusion, about two-thirds of leiomyoma patients were exposed to
      BPA, but it may not have growth promoting effect on leiomyoma. 

PMID- 24278552
TI  - Developing korean standard for nanomaterial exposure assessment.
AB  - Nanotechnology is now applied to many industries, resulting in wide range of
      nanomaterial-containing products, such as electronic components, cosmetic,
      medicines, vehicles, and home appliances. Nanoparticles can be released
      throughout the life cycle of nanoproducts, including the manufacture, consumer
      use, and disposal, thereby involving workers, consumers, and the environment in
      potential exposure. However, there is no current consensus on the best sampling
      method for characterizing manufactured-nanoparticle exposure. Therefore, this
      report aims to provide a standard method for assessing nanoparticle exposure,
      including the identification of nanoparticle emission, the assessment of worker
      exposure, and the evaluation of exposure mitigation actions in nanomaterial
      handling workplaces or research institutes. 

PMID- 24278553
TI  - Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ
      Toxicity in Sprague-Dawley Male Rats.
AB  - Brominated flame retardants (BFRs) are present in many consumer products ranging
      from fabrics to plastics and electronics. Wide use of flame retardants can pose
      an environmental hazard, which makes it important to determine the mechanism of
      their toxicity. In the present study, dose-dependent toxicity of
      tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male
      prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or
      500 mg/kg for 30 days. There were no differences in body weight gain between the
      control and TBBPA-treated groups. However, absolute and relative liver weights
      were significantly increased in high dose of TBBPA-treated groups. TBBPA
      treatment led to significant induction of CYP2B1 and constitutive androstane
      receptor (CAR) expression in the liver. In addition, serum thyroxin (T4)
      concentration was significantly reduced in the TBBPA treated group. These results
      indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in
      rats through the CAR signaling pathway. In particular, TBBPA efficiently produced
      reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8
      hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the
      kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA
      strongly induced the production of 8-OHdG in the testis and kidney. These
      observations suggest that TBBPA-induced target organ toxicity may be due to ROS
      produced by metabolism of TBBPA in Sprague- Dawley rats. 

PMID- 24278554
TI  - Inhibition of p65 Nuclear Translocation by Baicalein.
AB  - We demonstrate that baicalein, a bioactive flavonoid originally isolated from
      Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW
      264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with
      baicalein inhibited LPS-stimulated nitric oxide production in a dose-related
      manner. Immunohistochemical staining of iNOS and RT-PCR analysis showed that the
      decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7
      cells. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein
      inhibited NF-kappaB nuclear translocation, DNA binding, and transcriptional
      activation, respectively. Collectively, these series of experiments indicate that
      baicalein inhibits iNOS gene expression by blocking NF-kappaB nuclear
      translocation. Due to the critical role that NO release plays in mediating
      inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that
      baicalein may represent a useful anti-inflammatory agent. 

PMID- 24278555
TI  - Comparative Antitumor Activity of Different Solvent Fractions from an Auricularia
      auricula-judae Ethanol Extract in P388D1 and Sarcoma 180 Cells.
AB  - The objective of this study was to evaluate and compare the antitumor activity of
      different solvent fractions (ethanol, dichloromethane, ethyl acetate, butanol and
      water) of the Auricularia auricula-judae 70% ethanol extract on the P388D1
      macrophage and sarcoma 180 cells. A dose-dependent antitumor activity of each
      solvent fraction (from 0.01 mg/ml to 0.3 mg/ml) was shown against both cell
      types. These cytotoxic effects of all the tested fractions were confirmed on the
      MTT and SRB assays, without statistical differences each other. IC50 value of
      dichloromethane fraction was 94.2 MUg/ml against sarcoma 180 cells lower than any
      other solvent fractions. The potent antitumor effect of the dichloromethane (DCM)
      fraction was also found against solid tumor in BALB/c mice. The splenomegaly and
      higher splenic index were found in tumor-bearing mice, with the DCM fraction
      returning to the negative control values. Thus, the results indicated the
      dichloromethane fraction may have potential ingredients as antitumor candidates. 

PMID- 24278556
TI  - The Effect of Selective Estrogen Receptor Modulators (SERMs) on the Tamoxifen
      Resistant Breast Cancer Cells.
AB  - Selective estrogen receptor modulators (SERMs) are synthetic molecules which bind
      to estrogen receptors (ER) and can modulate its transcriptional capabilities in
      different ways in diverse estrogen target tissues. Tamoxifen, the prototypical
      SERM, is extensively used for targeted therapy of ER positive breast cancers.
      Unfortunately, the use of tamoxifen is associated with acquired resistance and
      some undesirable side effects. This study investigated the availability of the
      conventional SERMs on the TAM-resistance breast cancer cells. SERMs showed more
      effectiveness in MCF-7 cells than tamoxifen resistant cells, except toremifene
      and ospemifene. Especially, toremifene was more efficacious in tamoxifen
      resistant cells than MCF-7. Ospemifene had similar cytotoxic activity on the two
      types of breast cancers. The other SERMs used in this experiment didn't inhibit
      efficiently the proliferation of tamoxifen resistant cells. These results support
      the possibility to usage of toremifene on tamoxifen resistant cancer. The
      effectiveness by toremifene on tamoxifen resistant cells might be different
      pathways from the apoptosis and the autophagy. Further study should be needed to
      elucidate the underlying mechanism of effect of toremifene on tamoxifen resistant
      cancer. 

PMID- 24278557
TI  - Effect of DHU001, a Polyherbal Formula on Formalin-induced Paw Chronic
      Inflammation of Mice.
AB  - The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous
      extracts for various respiratory disorders were evaluated on the formalin-induced
      paw chronic inflammation in mice after oral administration. Mice were
      subaponeurotically injected in the left hind paw with 0.02 ml of 3.75% formalin,
      then subjected to 500, 250 and 125 mg/kg of DHU001 oral administration, once a
      day for 10 days during which then the hind-paw thickness and volume were measured
      daily. The paw wet-weight, histological profiles, histomorphometrical analyses
      and paw tumor necrosis factor (TNF)-alpha contents were conducted at termination.
      After two formalin treatments, a marked increase in the paw thickness and volume
      was detected in the formalin-injected control as compared with that in the intact
      control, plus at the time of sacrifice the paw wet-weights, paw TNF-alpha
      contents were also dramatically increased with severe chronic inflammation signs
      at histopathological observations. However, these formalin-induced chronic
      inflammatory changes were dramatically decreased by treatment of dexamethasone
      and all three different dosages of DHU001. DHU001 has favorable effects on
      formalin-induced chronic inflammation mediated by TNF-alpha suppression, and
      DHU001 may represent an alternative approach for the treatment of chronic
      inflammatory diseases. 

PMID- 24278558
TI  - Lipotoxicity of palmitic Acid on neural progenitor cells and hippocampal
      neurogenesis.
AB  - Lipotoxicity involves pathological alterations to cells and tissues in response
      to elevated fat levels in blood. Furthermore, this process can disturb both
      cellular homeostasis and viability. In the current study, the authors show that
      neural progenitor cells (NPCs) are vulnerable to high levels of palmitic acid
      (PA) a saturated fatty acid. PA was found to cause cell death associated with
      elevated reactive oxygen species (ROS) levels, and to reduce NPCs proliferation.
      To evaluate the lipotoxicity of PA in adult NPCs in the hippocampus, male C57BL/6
      mice were divided into two groups and maintained on either a normal diet (ND) or
      PA-rich high fat diet (HFD) for 2 weeks. Interestingly, short-term PA-rich HFD
      feeding reduced the survival of newly generated cells in the hippocampal dentate
      gyrus and hippocampal brain-derived neurotrophic factor levels. These findings
      suggest PA has a potent lipotoxicity in NPCs and that a PA-rich HFD disrupts
      hippocampal neurogenesis. 

PMID- 24278559
TI  - Toxicity Study of Streptococcus pneumoniae Vaccine Administrated Subcutaneously
      in Rats.
AB  - This study was performed to evaluate the toxicity of polysaccharide-based
      Streptococcus pneumoniae vaccine in Specific Pathogen Free (SPF), Sprague-Dawley
      (SD) rats. S. pneumoniae vaccine was administrated subcutaneously each dose level
      of high (560 MUg/rat), medium (280 MUg/rat) and low (140 MUg/rat) on days 0, 14,
      28. The rats were observed for 2 weeks or 4 weeks after the final injection.
      During this test, there were no significant dose-dependent changes in body
      weight, water and food consumption. In urinalysis and serum chemistry, dose
      related changes were not detected. In hematology, the percent of neutrophils and
      lymphocytes in white blood cells were changed significantly. According to the
      measurement of organ weight, only spleen weight was significantly increased in
      all groups of administration compared to the control group. In the
      histopathological examination, an antigen-deposit, vacuolated macrophages,
      infiltrated inflammatory cells and a formation of granulation tissue were
      observed at the site of an administration. These results are considered as an
      outcome by immune responses through a vaccination. Consequently, the results of
      this study demonstrated that S. pneumoniae vaccine has no toxicity when it was
      administrated subcutaneously three times in 2-week interval at a high dose of 560
      MUg/rat. 

PMID- 24278560
TI  - Micronucleus Test of Picrorrhiza Rhizoma Aqueous Extract in Bone Marrow Cells of
      Male ICR Mice.
AB  - In this research, the genotoxic effect of Picrorrhiza Rhizoma (PR) aqueous
      extract was evaluated using the mouse micronucleus test. PR extract was
      administered once a day for 2 continuous days by oral gavage to male ICR mice at
      doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic
      agent in a positive control. The appearance of a micronucleus (MN) in
      polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and
      PCE ratio is used as an index of cytotoxicity. Although significant (p < 0.01)
      increase of the number of PCE with one or more nuclei (MNPCE) was detected in
      cyclophosphamide treated groups, no significant increases of MNPCE numbers were
      observed in all three different dosages of PR extracts treated mice with over
      0.39 of the individual polychromatic erythrocyte ratio in all mice used in this
      study. The results obtained indicated that PR extract shows no genotoxicity
      effects up to 2000 mg/kg dosing levels. 

PMID- 24278561
TI  - Production of Group Specific Monoclonal Antibody to Aflatoxins and its
      Application to Enzyme-linked Immunosorbent Assay.
AB  - Through the present study, we produced a monoclonal antibody against aflatoxin B1
      (AFB1) using AFB1- carboxymethoxylamine BSA conjugates. One clone showing high
      binding ability was selected and it was applied to develop a direct competitive
      ELISA system. The epitope densities of AFB1-CMO against BSA and KLH were about 1
      : 6 and 1 : 545, respectively. The monoclonal antibody (mAb) from cloned
      hybridoma cell was the IgG1 subclass with lambda-type light chains. The IC50s of
      the monoclonal antibody developed for AFB1, AFB2, AFG1 and AFG2 were 4.36, 7.22,
      6.61 and 29.41 ng/ml, respectively, based on the AFB1-KLH coated ELISA system and
      15.28, 26.62, 32.75 and 56.67 ng/ml, respectively, based on the mAb coated ELISA.
      Cross-relativities of mAb to AFB1 for AFB2, AFG1 and AFG2 were 60.47, 65.97 and
      14.83% in the AFB1-KLH coated ELISA, and 59.41, 46.66 and 26.97% in the mAb
      coated ELISA, respectively. Quantitative calculations for AFB1 from the AFB1-Ab
      ELISA and AFB1-Ag ELISA ranged from 0.25 to 25 ng/ml (R(2) > 0.99) and from 1 to
      100 ng/ml (R(2) > 0.99), respectively. The intra- and inter-assay precision CVs
      were < 10% in both ELISA assay, representing good reproducibility of developed
      assay. Recoveries ranged from 79.18 to 91.27%, CVs ranged from 3.21 to 7.97%
      after spiking AFB1 at concentrations ranging from 5 to 50 ng/ml and following by
      extraction with 70% methanol solution in the Ab-coated ELISA. In conclusion, we
      produced a group specific mAb against aflatoxins and developed two direct
      competitive ELISAs for the detection of AFB1 in feeds based on a monoclonal
      antibody developed. 

PMID- 24278562
TI  - A New Way in Deciding NOAEL Based on the Findings from GLP-Toxicity Test.
AB  - The FDA guidance focuses on the use of the NOAEL to establish the maximum
      recommended starting dose. The majority of NOAEL has been described inaccurately
      or incompletely in final reports for 90-days repeated dose toxicity test based on
      GLP (good laboratory practice) regulation. This is the most serious one of
      reasons for why most pharmaceutical companies targeting global markets have
      disregarded the final report produced from GLP facilities in Korea. The problems
      in deciding NOAEL reflected in the final reports are mainly due to the
      followings; 1) Inaccurate description or use of NOEL, NOAEL and LOAEL, 2)
      Insufficient and inappropriate interpretations in findings from toxicity test.
      This paper is intended to provide the insight into distinguishing NOAEL from NOEL
      and LOAEL, and into classifying findings from toxicity test. Here, the three step
      method is newly suggested by applying the weight-based classification to the
      NOEL, NOAEL and LOAEL based on the findings. 

PMID- 24278563
TI  - Risk Assessment of Baby Powder Exposure through Inhalation.
AB  - This study was conducted to assess the exposure risk through inhalation to baby
      powder for babies and adults under simulated conditions. Baby powder was applied
      to a baby doll and the amount of baby powder consumed per application was
      estimated. The airborne exposure to baby powder during application was then
      evaluated by sampling the airborne baby powder near the breathing zones of both
      the baby doll and the person applying the powder (the applicator). The average
      amount of baby powder consumed was 100 mg/application, and the average exposure
      concentration of airborne baby powder for the applicator and baby doll was
      0.00527 mg/m(3) (range 0.00157~0.01579 mg/m(3)) and 0.02207 mg/m(3) (range
      0.00780~ 0.04173 mg/m(3)), respectively. When compared with the Occupational
      Exposure Limit of 2 mg/m(3) set by the Korean Ministry of Labor and the Threshold
      Limit Value (TLV) of 2 mg/m(3) set by the ACGIH (American Conference of
      Governmental Industrial Hygienists), the exposure concentrations were much lower.
      Next, the exposure to asbestos-containing baby powder was estimated and the
      exposure risk was assessed based on the lung asbestos contents in normal humans.
      As a result, the estimated lung asbestos content resulting from exposure to
      asbestos-containing baby powder was found to be much lower than that of a normal
      Korean with no asbestos-related occupational history. 

PMID- 24278564
TI  - Determination of optimal toxic concentration and accumulation of cadmium in
      broiler chicks.
AB  - Cadmium is considered one of the most toxic, non biodegradable heavy metal for
      the human and animals. The purpose of the present study was to investigate the
      changes in biochemical parameters of blood and accumulation of cadmium in various
      tissue caused by various levels of dietary cadmium chloride (CdCl2) in broiler
      chicks. CdCl2 was administered through drinking water to broiler chicks. In
      spectral analysis, CdCl2 treatment caused a significant increase in Glutamate
      pyruvate transaminase (GPT), creatinine and uric acid levels in all treated
      groups. Intriguingly, the GPT, creatinine, and uric acid levels were
      significantly higher at 75 mg/kg as compared to the groups treated with high
      doses (100, 125 and 150 mg/kg) of CdCl2. Atomic Absorption Spectrophotometer
      (AAS) was used for the determination of Cd accumulation in kidney, liver and
      Breast muscles. AAS analysis revealed that Cd accumulation is increased in breast
      muscles as compared to liver and kidney at higher doses of Cd than 75 mg/kg. 

PMID- 24278565
TI  - Spontaneous multicentric malignant schwannoma in a male Fischer 344 rat.
AB  - We describe here a multicentric spontaneous malignant schwannoma obtained from
      one male F344 rat, and this animal was the subject of a carcinogenicity study for
      which it was treated with diisodecyl phthalate. The animal of the control group
      not treated with diisodecyl phthalate showed dyspnea and severe lordosis. On the
      necropsy, two tan, firm, encapsulated masses were observed in the subcutis of the
      lumbosacral region and the left inguinal region of the abdominal cavity,
      respectively; the masses were 25 * 17 * 8 mm and 16 * 14 * 8 mm in size,
      respectively. Histologically, the tumor consisted of spindle and pleomorphic
      cells that grew in various patterns, that was, sweeping fascicles and herringbone
      and local organoid patterns. The pleomorphic neoplastic cells had more than two
      nuclei. Additionally, the diagnosis of malignant schwannoma was confirmed by the
      immune reactivity of the tumor cells for S-100 protein. 

PMID- 24278566
TI  - Whitening effect of black tea water extract on brown Guinea pig skin.
AB  - To evaluate the whitening effect of black tea water extract (BT), BT was
      topically applied to artificially hyperpigmented spots on the back skins of brown
      guinea-pigs (weight: 450~500 g) induced by 1,500 mJ/ cm(2) of ultraviolet B (UVB)
      irradiation. The test compounds of 30 MUl were applied twice a day, six days a
      week, for four weeks. The artificially hyperpigmented spots were divided into 5
      groups: control (UVB + saline, C), vehicle control [UVB + propylene glycol:
      ethanol: water (5 : 3 : 2), VC], positive control (UVB + 2% hydroquinone, PC),
      experimental 1 (UVB + 1% BT), experimental 2 (UVB + 2% BT). After 4-week
      application, the spots were removed by biopsy punch under anesthetic condition
      and used as specimens for the histological examination. The total polyphenol and
      flavonoid contents of BT were 104 and 91 mg/g, respectively. The electron
      donating ability of BT revealed a dose-dependent response, showing the excellent
      capacities of 86% at 800 MUg/ml. The artificially hyperpigmented spots treated
      with the PC and BT were obviously lightened compared to the C and VC groups. At
      the fourth week, the melanin indices for the PC and BT groups were significantly
      lower (p < 0.00l) than those of the C and VC groups. In histological examination,
      PC and BT groups were significantly reduced in the melanin pigmentation, the
      proliferation of melanocytes and the synthesis of melanosomes compared to the C
      and VC groups. It is found that BT inhibits the proliferation of melanocytes and
      synthesis of melanosomes in vivo using brown guinea pigs, thereby showing a
      definite skin whitening effect. 

PMID- 24278567
TI  - Generation of reactive oxygen species contributes to the development of carbon
      black cytotoxicity to vascular cells.
AB  - Carbon black, a particulate form of pure elemental carbon, is an industrial
      chemical with the high potential of occupational exposure. Although the
      relationship between exposure to particulate matters (PM) and cardiovascular
      diseases is well established, the cardiovascular risk of carbon black has not
      been characterized clearly. In this study, the cytotoxicity of carbon black to
      vascular smooth muscle and endothelial cells were examined to investigate the
      potential vascular toxicity of carbon black. Carbon black with distinct particle
      size, N330 (primary size, 28~36 nm) and N990 (250~350 nm) were treated to A-10,
      rat aortic smooth muscle cells and human umbilical vein endothelial cell line,
      ECV304, and cell viability was assessed by lactate dehydrogenase (LDH) leakage
      assay. Treatment of carbon black N990 resulted in the significant reduction of
      viability in A-10 cells at 100 MUg/ml, the highest concentration tested, while
      N330 failed to cause cell death. Cytotoxicity to ECV304 cells was induced only by
      N330 at higher concentration, 200 MUg/ml, suggesting that ECV304 cells were
      relatively resistant to carbon black. Treatment of 100 MUg/ml N990 led to the
      elevation of reactive oxygen species (ROS) detected by dichlorodihydrofluorescein
      (DCF) in A-10 cells. Pretreatment of antioxidants, N-acetylcysteine (NAC) and
      sulforaphane restored decreased viability of N990-treated A-10 cells, and N
      acetylcysteine, but not sulforaphane, attenuated N990-induced ROS generation in A
      10 cells. Taken together, present study shows that carbon black is cytotoxic to
      vascular cells, and the generation of reactive oxygen contributes to the
      development of cytotoxicity. ROS scavenging antioxidant could be a potential
      strategy to attenuate the toxicity induced by carbon black exposure. 

PMID- 24278568
TI  - Macrophage activation by glycoprotein isolated from Dioscorea batatas.
AB  - We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) activates
      macrophage function. Analysis of the infiltration of macrophages into peritoneal
      cavity showed GDB treatment significantly increased the recruitment of
      macrophages into the peritoneal cavity. In order to further confirm and
      investigate the mechanism of GDB on macrophage activation, we analyzed the
      effects of GDB on the cytokine expression including IL-1beta, TNF-alpha, and IL-6
      in mouse peritoneal macrophages. GDB increased the expression of IL-1beta, TNF
      alpha, and IL-6. Cytokine induction by GDB was further confirmed by RT-PCR and
      ELISA in mouse macrophage cell line, RAW264.7 cells. Treatment of RAW264.7 cells
      with GDB produced strong induction of NF-kappaB DNA binding and MAPK
      phosphorylation, markers for macrophage activation and important factors for
      cytokine gene expression. Collectively, this series of experiments indicates that
      GDB stimulates macrophage activation. 

PMID- 24278569
TI  - The Inhibitory Effect of Premature Citrus unshiu Extract on Atopic Dermatitis In
      Vitro and In Vivo.
AB  - Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is
      associated with Th2 cellmediated allergy. The process that leads to infiltration
      of inflammatory cells into an AD lesion is remarkably dependent on various
      chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and
      MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are
      over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin,
      has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore,
      we investigated the effect of EtOH extract of premature C. unshiu on AD. We did
      this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory
      effect for premature C. unshiu on the expression of inflammatory chemokines in
      IFN-gamma and TNF-alpha stimulated HaCaT human keratinocytes. We found that
      extract of premature C. unshiu reduced DNCB-induced symptoms such as
      hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD
      like animal model. The extract decreased levels of IFN-gamma and IL-4 in ConA
      stimulated splenocytes isolated from DNCB-treated mice. Also, extract of
      premature C. unshiu inhibited mRNA expression and protein production of TARC and
      MDC through the inhibition of STAT1 phosphorylation. These results suggest that
      C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as
      TARC and MDC. 

PMID- 24278570
TI  - Estrogenic Activity of Persistent Organic Pollutants and Parabens Based on the
      Stably Transfected Human Estrogen Receptor-alpha Transcriptional Activation Assay
      (OECD TG 455).
AB  - Screening of estrogenic activity on dichloro diphenyl trichloroethane (DDT),
      dichloro diphenyl dichloro ethylene (DDE), dieldrin, heptachlor, aldrin,
      chlordane, lindane, polybrominated diphenyl ethers (PBDE) and parabens was
      compared using Organization for Economic Cooperation and Development (OECD) test
      guideline 455 (TG455). The estrogenic activity of DDT was 58,000-fold (PC50, 1.67
      * 10(-6) M) less than 17beta-estradiol(E2) (PC50, 2.88 * 10(-11) M) but DDE,
      dieldrin, heptachlor, aldrin, chlordane, lindane and PBDE did not show any
      estrogenic activity in this assay system. In the case of paraben compounds, the
      rank of relative transcriptional activation (logRTA) was butyl paraben -1.63752
      (PC50, 1.25 * 10(-7)M) > isobutyl paraben -2.34008 (PC50, 6.3 * 10(-7)M) > ethyl
      paraben -2.64016 (PC50, 1.26 * 10(-6) M) > isopropyl paraben -2.73993 (PC50, 1.58
      * 10(-6)M) > propyl paraben -2.84164 (PC50, 2.0 * 10(-6) M). Our data suggest
      that OECD test guideline TG455 may be useful as a screening tool for potential
      endocrine disruptors. 

PMID- 24278571
TI  - Effect of Di-(2-ethylhexyl)-phthalate on Sphingolipid Metabolic Enzymes in Rat
      Liver.
AB  - Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer
      and a ubiquitous environmental contaminant, can act on peroxisome proliferators
      activated nuclear hormone receptor family (PPAR) isoforms. To understand the
      contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of
      DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was
      investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through
      oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases
      were slightly increased in 250 mg/kg DEHP-administered rat livers and
      significantly elevated in 500 mg/kg DEHP-administered ones, although the level of
      750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic
      and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were
      not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases
      might play important roles in DEHP-induced hepatotoxicity. 

PMID- 24278573
TI  - The Comparative Evaluation of Fermented and Non-fermented Soybean Extract on
      Antioxidation and Whitening.
AB  - The present study was performed to compare the antioxidative and whitening
      activities of fermented soybean extract (FSB) and non-fermented soybean extract
      (SB). Antioxidative and whitening activities of FSB and SB were evaluated by the
      determination of DPPH, superoxide radical and hydroxyl radical scavenging
      activities, linoleic acid inhibition activity, and tyrosinase inhibition
      activity. FSB showed the higher effect than SB in the antioxidative activities.
      Also FSB showed the better effect than SB in whitening activity. These results
      demonstrated that the fermentation played a more excellent role than the non
      fermentation in antioxidation and whitening. Therefore, this study suggested that
      FSB could be a useful cosmetic ingredient for antioxidation and skin whitening. 

PMID- 24278572
TI  - Toxicological characterization of phthalic Acid.
AB  - There has been growing concern about the toxicity of phthalate esters. Phthalate
      esters are being used widely for the production of perfume, nail varnish,
      hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has
      been assessed by analyzing urine for their metabolites. The parent phthalate is
      rapidly metabolized to its monoester (the active metabolite) and also
      glucuronidated, then excreted. The objective of this study is to evaluate the
      toxicity of phthalic acid (PA), which is the final common metabolic form of
      phthalic acid esters (PAEs). The individual PA isomers are extensively employed
      in the synthesis of synthetic agents, for example isophthalic acid (IPA), and
      terephthalic acid (TPA), which have very broad applications in the preparation of
      phthalate ester plasticizers and components of polyester fiber, film and
      fabricated items. There is a broad potential for exposure by industrial workers
      during the manufacturing process and by the general public (via vehicle exhausts,
      consumer products, etc). This review suggests that PA shows in vitro and in vivo
      toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In
      addition, PA seems to be a useful biomarker for multiple exposure to PAEs in
      humans. 

PMID- 24278574
TI  - Effects of Medicinal herb Extracts and their Components on Steatogenic
      Hepatotoxicity in Sk-hep1 Cells.
AB  - Herbal medicines are widely used in many countries for the treatment of many
      diseases. Although the use of herb extracts as alternative medicine is growing,
      their toxicological properties have not been thoroughly investigated. In this
      study, we have investigated the effects of water and ethanol extracts of 18 herbs
      on the hepatic lipid metabolism and steatogenic hepatotoxicity. Ethanol extracts
      of Cirsium japonicum, Carthamus tinctorius, Rehmanniae glutinosa (preparata),
      Polygala tenuifolia, Foeniculum vulgare, Polygonum multiflorum, and Acorus
      gramineus and water extracts of Polygonum multiflorum and Rehmanniae glutinosa
      induced lipid accumulation in Sk-hep1 human hepatoma cells as determined by Nile
      red staining. These extracts increased the luciferase activity of sterol
      regulatory element (SRE) and decreased that of peroxisome proliferator response
      element (PPRE), indicating the possibilities of enhanced fatty acid synthesis and
      decreased fatty acid oxidation. To identify the components responsible for the
      fat accumulation, we tested 50 chemicals isolated from the nine herbs. Apigenin,
      luteolin, pectolinarin and lupeol from Cirsium japonicum, 8-methoxypsoralen and
      umbelliferone from Foeniculum vulgare and pomonic acid and jiocerebroside from
      Rehmanniae glutinosa significantly increased the accumulation of lipid droplets.
      These results suggest that ethanol extracts of Cirsium japonicum, Carthamus
      tinctorius, Rehmanniae glutinosa (preparata), Polygala tenuifolia, Foeniculum
      vulgare, Polygonum multiflorum, and Acorus gramineus and water extracts of
      Polygonum multiflorum and Rehmanniae glutinosa can cause fatty liver disease by
      decreasing beta-oxidation of fatty acid and increasing lipogenesis. 

PMID- 24278575
TI  - Single oral dose toxicity test of platycodin d, a saponin from platycodin radix
      in mice.
AB  - The object of this study was to evaluate the single oral dose toxicity of
      platycodin D, a saponin from the root of Platycodon grandiflorum in male and
      female mice. Platycodin D was administered to female and male mice as an oral
      dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for
      the mortality and changes in body weight, clinical signs and gross observation
      during 14 days after treatment, upon necropsy, organ weight and histopathology of
      14 principle organs were examined. As the results, no platycodin D treatment
      related mortalities, clinical signs, changes on the body and organ weights, gross
      and histopathological observations against 14 principle organs were detected up
      to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and
      approximate LD of playtcodin D after single oral treatment in female and male
      mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA
      Guidelines [2009-116, 2009], respectively. 

PMID- 24278577
TI  - Thirteen-Week Oral Dose Toxicity Study of G. bimaculatus in Sprague-Dawley Rats.
AB  - Gryllus bimaculatus (Gb) was orally administered at doses of 0, 0.04, 0.2, 1 and
      5 g/kg bw/day for 13 consecutive weeks. There were no observed clinical signs or
      deaths related to treatment in all the groups tested. Therefore, the approximate
      lethal oral dose of G. bimaculatus was considered to be higher than 5 g/kg in
      rats. Throughout the administration period, no significant changes in diet
      consumption, ophthalmologic findings, organ weight, clinical pathology
      (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology
      were detected. Minor changes were found in hematological parameters for the 5
      g/kg Gb-treated group (triglyceride reduction of 35.8%), but all changes were
      within normal physiological ranges. Microscopic examination did not identify any
      treatment-related histopathologic changes in the organs of Gb-treated rats in the
      high dose group. From these results, one can conclude that the no-observed
      adverse effect level (NOAEL) of G. bimaculatus is higher than 5 g/kg bw/day in
      rats. 

PMID- 24278576
TI  - Skin Hydration and Collagen Synthesis of AF-343 in HS68 Cell Line and NC/Nga Mice
      by Filaggrin Expression and Suppression of Matrix Metallopreteinase.
AB  - Extract of Taraxacum platycarpum (AF-343) has been reported to have several
      biological properties such as skin hydration and anti-inflammatory effects.
      Although clinical evidences of skin hydration and antiinflammatory effect were
      proven in clinical trial, precise mechanism of skin hydration was not fully
      understood yet. In this study, we have focused skin hydration mechanism related
      filaggrin, collagen, and matrix metalloproteinase (MMP) in vitro and animal
      study. Herein, skin hydration mechanism of AF-343 is due to recovery of filaggrin
      in mice model and increased production of collagen with suppression of matrix MMP
      in vitro fibroblast cell line. 

PMID- 24278578
TI  - Isolation of Soil Microorganisms Having Antibacterial Activity and Antimigratory
      Effects on Sphingosylphosphorylcholine-induced Migration of PANC-1 Cells.
AB  - To obtain soil microorganisms producing antimigratory activity which is important
      in controlling the metastasis of cancer cells, more than three hundreds of soil
      microbes were isolated from sixteen soil sources including Namsan mountain and
      designated as DGU1001-10338. At first, their antibiotic activities were examined
      by paper-disc method. More than 40 soil microbes produced compounds with
      antibiotic activity. Then, antimigratory activities of selected soil
      microorganisms were examined in a sphingosylphosphorylcholine-induced migration
      assay in PANC-1 cells. Six of 42 soil microorganisms having antibacterial
      activity also had more than 45% inhibitory activity on migration of PANC-1 cells.
      These results suggested that selected soil microorganisms were a useful starting
      point to find compounds for controlling metastasis of cancer cells. 

PMID- 24278579
TI  - Decreased Diethylnitrosamine-induced Liver Preneoplastic Lesions by Estradiol-3
      benzoate Treatment.
AB  - To clarify whether inhibitory effect of estrogen on liver tumor is associated
      with cell proliferation, we investigated its role in diethylnitrosamine (DEN)
      induced rat preneoplastic lesions, with time sequenced manners. F344 male rats (n
      = 90) were divided into three groups at 5 weeks of age. The mini-osmotic pumps
      providing a continuous infusion of DEN was implanted into the abdominal cavity of
      each animal in group 1, 2 and 3 at 6 weeks of age. To see the effect of estrogen,
      pellet containing 1 or 10 MUg of estradiol- 3-benzoate (EB) was implanted
      subcutaneously in the animals of groups 2 or 3, respectively, one week prior to
      DEN treatment. Ten animals of each group were euthanized at 10, 14 and 18 weeks
      after DEN treatment. Liver tissues at each time point were fixed in 10% phosphate
      buffered formalin and were processed and embedded in paraffin and 5 MUm sections
      mounted on a silanized slide. Glutathione S-transferase placental form (GST-P)
      positive foci and 5-bromo-2-deoxyuridine (BrdU) labeling cells were detected at
      each time point. Area of GST-P positive foci in DEN+EB 1 or 10 MUg group was
      significantly decreased compared to DEN alone at 14 weeks (p < 0.01 or p < 0.05,
      respectively) an at 18 weeks (p < 0.05 or p < 0.01, respectively). BrdU index in
      DEN+EB 1 or 10 MUg groups was significantly decreased compared to DEN alone at 14
      weeks and at 18 weeks (p < 0.01). Taken together, we conclude that EB treatment
      decrease the DEN-induced liver preneoplastic lesions and this may be associated
      with decrease of cellular proliferation. 

PMID- 24278581
TI  - Four-Week Repeated Oral Toxicity Study of AIP1, a Water-soluble Carbohydrate
      Fraction from Artemisia iwayomogi in Mice.
AB  - Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found
      in Korea and used as a traditional medicine to treat liver disease. AIP1, a water
      soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and
      immuno-modulating activities in animal studies. A subacute toxicological
      evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of
      AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight
      changes, hematology, blood clinical biochemistry, urinalysis, organ
      histopathology, organ weights and gross finding were examined. The results showed
      that there were no significant differences in body weight changes, food intakes,
      water consumptions, or organ weights among different dose groups. Also we
      observed no death and abnormal clinical signs during the experimental period.
      Between the groups orally treated with AIP1 and the control group, there was no
      statistical significance in hematological test or serum biochemical values.
      Histopathological examination showed no abnormal changes in AIP1 groups. These
      results suggest that no observed adverse effect level (NOAEL) of the oral
      administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/ day
      in mice under the condition investigated in current study. 

PMID- 24278580
TI  - Cell Growth of BG-1 Ovarian Cancer Cells was Promoted by 4-Tert-octylphenol and 4
      Nonylphenol via Downregulation of TGF-beta Receptor 2 and Upregulation of c-myc.
AB  - Transforming growth factor beta (TGF-beta) is involved in cellular processes
      including growth, differentiation, apoptosis, migration, and homeostasis.
      Generally, TGF-beta is the inhibitor of cell cycle progression and plays a role
      in enhancing the antagonistic effects of many growth factors. Unlike the
      antiproliferative effect of TGF-beta, E2, an endogeneous estrogen, is stimulating
      cell proliferation in the estrogen-dependent organs, which are mediated via the
      estrogen receptors, ERalpha and ERbeta, and may be considered as a critical risk
      factor in tumorigenesis of hormone-responsive cancers. Previous researches
      reported the cross-talk between estrogen/ERalpha and TGF-beta pathway.
      Especially, based on the E2-mediated inhibition of TGF-beta signaling, we
      examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP),
      which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on
      TGF-beta signaling via semi-quantitative reverse-transcription PCR. The treatment
      of E2, OP, or NP resulted in the downregulation of TGF- beta receptor2 (TGF-beta
      R2) in TGF-beta signaling pathway. However, the expression level of TGF-beta1 and
      TGF- beta receptor1 (TGF-beta R1) genes was not altered. On the other hand, E2,
      OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc,
      which is a oncogene and a downstream target gene of TGF-beta signaling pathway.
      As a result of downregulation of TGF-beta R2 and the upregulation of c-myc, E2,
      OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken
      together, these results suggest that E2 and these two EDCs may mediate cancer
      cell proliferation by inhibiting TGF-beta signaling via the downregulation of TGF
      beta R2 and the upregulation of c-myc oncogene. In addition, it can be inferred
      that these EDCs have the possibility of tumorigenesis in estrogen-responsive
      organs by certainly representing estrogenic effect in inhibiting TGF-beta
      signaling. 

PMID- 24278582
TI  - Skin Sensitization Study of Bee Venom (Apis mellifera L.) in Guinea Pigs.
AB  - Bee venom (Apis mellifera L., BV) has been used as a cosmetic ingredient for
      antiaging, anti-inflammatory and antibacterial functions. The aim of this study
      was to access the skin sensitization of BV, a Buehler test was conducted fifty
      healthy male Hartley guinea pigs with three groups; Group G1 (BVsensitization
      group, 20 animals), group G2 (the positive control-sensitization group, 20
      animals), and group G3 (the ethyl alcohol-sensitization group, 10 animals). The
      exposure on the left flank for induction was repeated three times at intervals of
      one week. Two weeks after the last induction, the challenge was performed on the
      right flank. No treatment-related clinical signs or body weight changes were
      observed during the study period. The average skin reaction evaluated by erythema
      and edema on the challenge sites and sensitization rate in the BV-sensitization
      group at 30 hours were 0.0 and 0%, respectively, which are substantially low
      compared with in positive control group (average skin reaction: 0.55,
      sensitization rate: 40%) and identical with in vehicle control group,
      representing a weak sensitizing potential. The average skin reaction and
      sensitization rate observed at 54 hours were 0.0 and 0% in the BV-sensitization
      group, respectively, and 0.25 and 20% in the positive control group,
      respectively. It was concluded that BV classified to Grade I, induced no
      sensitization when tested in guinea pigs and may provide a developmental basis
      for a cosmetic ingredient or external application for topical uses. 

PMID- 24278583
TI  - Synthetic prion Peptide 106-126 resulted in an increase matrix metalloproteinases
      and inflammatory cytokines from rat astrocytes and microglial cells.
AB  - It has been shown that the accumulation of prion in the cytoplasm can result in
      neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a
      glycoprotein that is expressed predominantly by neurons and other cells,
      including glial cells. Prion-induced chronic neurodegeneration has a substantial
      inflammatory component, and an increase in the levels of matrix
      metalloproteinases (MMPs) may play an important role in neurodegenerative
      development and progression. However, the expression of MMPs in PrP induced rat
      astrocytes and microglia has not yet been compared. Thus, in this study, we
      examined the fluorescence intensity of CD11b positive microglia and Glial
      Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the
      fluorescent intensity was increased following incubation with PrP at 24 hours in
      a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL
      1beta) and tumor necrosis factor alpha (TNF-alpha) protein expression, which are
      initial inflammatory cytokines, in both PrP induced astrocytes and microglia.
      Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes
      and microglia was observed by real time PCR. Our results demonstrated PrP induced
      activation of astrocytes and microglia respectively, which resulted in an
      increase in inflammatory cytokines and MMPs expression. These results provide the
      insight into the different sensitivities of glial cells to PrP. 

PMID- 24278584
TI  - Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.
AB  - The aim of this study was to evaluate the single oral dose toxicity of Bupleuri
      Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory
      agent, in male and female mice. BR extracts (yield = 16.52%) was administered to
      female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body
      weight) according to the recommendation of Korea Food and Drug Administration
      (KFDA) Guidelines. Animals were monitored for the mortality and changes in body
      weight, clinical signs and gross observation during 14 days after dosing, upon
      necropsy; organ weight and histopathology of 14 principal organs were examined.
      As the results, no BR extracts treatment related mortalities, clinical signs,
      changes on the body and organ weights, gross and histopathological observations
      against 14 principal organs were detected up to 2,000 mg/kg in both female and
      male mice, except for soft feces and related body weight decrease detected in
      male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and
      approximate LD of BR aqueous extracts after single oral treatment in female and
      male mice were considered over 2000 mg/kg, respectively. Although it was also
      observed that the possibilities of digestive disorders, like soft feces when
      administered over 2,000 mg/kg of BR extracts in the present study, these
      possibilities of digestive disorders can be disregard in clinical use because
      they are transient in the highest dosages male only. 

PMID- 24278585
TI  - Involvement of Caenohabditis elegans MAPK Signaling Pathways in Oxidative Stress
      Response Induced by Silver Nanoparticles Exposure.
AB  - In the present study, toxicity of silver nanoparticles (AgNPs) was investigated
      in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway
      responsible for regulating oxidative stress, such as mitogen-activated protein
      kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed
      in AgNPs exposed C.elegans, suggesting oxidative stress as an important mechanism
      in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK
      signaling pathways increased by AgNPs exposure in less than 2-fold compared to
      the control in wildtype C.elegans, however, those were increased dramatically in
      sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk
      2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on
      the expression of oxidative stress response genes suggest that sod-3 gene
      expression appears to be dependent on p38 MAPK activation. The high expressions
      of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be
      interpreted as compensatory mechanisms in the absence of important stress
      response genes. Overall results suggest that MAPK-based integrated stress
      signaling network seems to be involved in defense to AgNPs exposure in C.elegans.

PMID- 24278586
TI  - Acute pulmonary toxicity and body distribution of inhaled metallic silver
      nanoparticles.
AB  - The purpose of this study was to determine the acute pulmonary toxicity of
      metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary
      toxicity and body distribution of inhaled MSNPs in mice were evaluated using a
      nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid
      analysis, Western blotting, histopathological changes, and silver burdens in
      various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The
      mean concentration, total surface area, volume and mass concentrations in the
      NOEC were maintained at 1.93 * 10(7) particles/cm(3), 1.09 * 10(10) nm(2)/cm(3),
      2.72 * 10(11) nm(3)/cm(3), and 2854.62 MUg/m(3), respectively. Inhalation of
      MSPNs caused mild pulmonary toxicity with distribution of silver in various
      organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the
      lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein
      kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild
      pulmonary toxicity, which was associated with activated MAPK signaling. Taken
      together, our results suggest that the inhalation toxicity of MSNPs should be
      carefully considered at the molecular level. 

PMID- 24278587
TI  - Methanolic Extract Isolated from Root of Lycoris aurea Inhibits Cancer Cell
      Growth and Endothelial Cell Tube Formation In Vitro.
AB  - In this study, we investigated the effect of methanolic extract isolated from the
      root of Lycoris aurea (LA) on the growth of cancer cells and the tube formation
      activity of endothelial cells. Various cancer cells were treated with LA at doses
      of 0.3, 1, 3, 10 or 30 MUg/ml and LA significantly suppressed the growth of
      several cancer cell lines, including ACHN, HCT-15, K-562, MCF-7, PC-3 and SK-OV
      3, in a dose-dependent manner. We also found that LA induced cell cycle arrest at
      G2/M phase in ACHN renal cell adenocarcinoma cells. Further study demonstrated
      that LA concentration-dependently inhibited the tube formation, which is a widely
      used in vitro model of reorganization stage of angiogenesis, in human umbilical
      vein endothelial cells. Collectively, these results show that LA inhibits the
      growth of cancer cells and tube formation of endothelial cells and the growth
      inhibitory effect of LA might be mediated, at least in part, by blocking cell
      cycle progression. 

PMID- 24278588
TI  - Suppressive effect of zinc on the formation of colonic preneoplastic lesions in
      the mouse fed high levels of dietary iron.
AB  - We investigated the effect of zinc on the formation of colonic aberrant crypt
      foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in
      mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on
      high iron diets with combination of three different levels of zinc in diets, low
      zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for
      12 weeks. Animals were received weekly intraperitoneal injections of AOM (10
      mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight
      36,000~50,000) in the drinking water for a week. To confirm the iron storage in
      the body, the hepatic iron concentration has been determine chemically and
      compared with histological assessment visualized by Prussian blue reaction.
      Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic
      mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and
      thiobarbituric acid-reactive substances (TBARS) level were also investigated.
      Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl
      transferase-mediated dUTP nickend labeling (TUNEL). In addition,
      immunohistochemistry of beta-catenin was also performed on the mucous membrane of
      colon. The number of large ACF (>= 4 AC/ACF), which possess greater tumorigenic
      potential, was significantly lower in MZn and HZn groups compared with LZn group.
      Cytosolic SOD activity in the liver was significantly higher in HZn group
      compared with LZn group. Hepatic MDA level was decreased significantly in HZn
      group compared with MZn and LZn groups. Apoptotic index was significantly higher
      in HZn group. Taken together, these findings indicate that dietary zinc might
      exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS
      in ICR mice with high iron status, and suggest that dietary supplement of zinc
      might play a role in suppressing colon carcinogenesis in mice. 

PMID- 24278589
TI  - The Safety Evaluation of a Potent Angiogenic Activator, Synthetic Peptide (SFKLRY
      NH2) for the Skin Application.
AB  - A novel synthetic hexapeptide (SFKLRY-NH2) that displays angiogenic activity has
      been identified by positional scanning of a synthetic peptide combinatorial
      library (PS-SPCL). This study was carried out to investigate the irritation of
      the SFKLRY-NH2 on the skin. The tests were performed on the basis of Korea Food
      and Drug Administration (KFDA) guidelines. In results, cell toxicity is not
      appeared for SFKLRY-NH2 in HaCaT cells and B16F10 cells. SFKLRY-NH2 induced no
      skin irritation at low concentration (10 MUM), mild irritation at high
      concentration (10mM). We consider that this result is helpful for saying about
      the safety of SFKLRY-NH2 in clinical use. 

PMID- 24278590
TI  - The Toxicity and Anti-cancer Activity of the Hexane Layer of Melia azedarach L.
      var. japonica Makino's Bark Extract.
AB  - In this study, the 4-week oral toxicity and anti-cancer activity of the hexane
      layer of Melia azedarach L. var. japonica Makino's bark extract were
      investigated. We carried out a hollow fiber (HF) assay and 28- day repeated
      toxicity study to confirm the anti-cancer effect and safety of the hexane layer.
      The HF assay was carried out using an A549 human adenocarcinoma cell via
      intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg
      b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the
      highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated
      toxicity study, 6 groups of 10 male and female mice were given by gavage 200,
      100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin
      against body weight, and were then sacrificed for blood and tissue sampling. The
      subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w
      hexane layer showed no significant changes in body weight gain and general
      behavior. The cisplatin-treated group significantly decreased in body weight
      compared to the control group but regained weight with 100 and 200 mg/kg b.w of
      hexane layer. The biochemical analysis showed significant increase in several
      parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated
      groups. However, in the group given a co-treatment of hexane layer (200 mg/kg
      b.w), levels of these parameters decreased. In hematological analysis, cisplatin
      induced the reduction of WBCs and neutrophils but co-treatment with hexane layer
      (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The
      histological profile of the livers showed eosinophilic cell foci in central vein
      and portal triad in cisplatin treated mice. These results show that hexane layer
      might have an anti-cancer activity and could improve the toxicity of cisplatin. 

PMID- 24278591
TI  - Toxicological investigation of radioactive uranium in seawater.
AB  - Trace uranium detection measurement was performed using DNA immobilized on a
      graphite pencil electrode (DGE). The developed probe was connected to the
      portable handheld voltammetric systems used for seawater analysis. The sensitive
      voltammogram was obtained within only 30 s accumulation time, and the anodic
      stripping working range was attained at 100~800 MUg/l U and 10~50 MUg/l. The
      statistic relative standard deviation of 30.0 mg/l with the 15(th) stripping was
      0.2115. Here, toxicological and analytical application was performed in the
      seawater survey in a contaminated power plant controlling water. The results were
      found to be applicable for real-time toxicological assay for trace control. 

PMID- 24278592
TI  - Risk assessment principle for engineered nanotechnology in food and drug.
AB  - While the ability to develop nanomaterials and incorporate them into products is
      advancing rapidly worldwide, understanding of the potential health safety effects
      of nanomaterials has proceeded at a much slower pace. Since 2008, Korea Food and
      Drug Administration (KFDA) started an investigation to prepare "Strategic Action
      Plan" to evaluate safety and nano risk management associated with foods, drugs,
      medical devices and cosmetics using nano-scale materials. Although there are some
      studies related to potential risk of nanomaterials, physical-chemical
      characterization of nanomaterials is not clear yet and these do not offer enough
      information due to their limitations. Their uncertainties make it impossible to
      determine whether nanomaterials are actually hazardous to human. According to the
      above mention, we have some problems to conduct the human exposure risk
      assessment currently. On the other hand, uncertainty about safety may lead to
      polarized public debate and to businesses unwillingness for further
      nanotechnology investigation. Therefore, the criteria and methods to assess
      possible adverse effects of nanomaterials have been vigorously taken into
      consideration by many international organizations: the World Health Organization,
      the Organization for Economic and Commercial Development and the European
      Commission. The object of this study was to develop risk assessment principles
      for safety management of future nanoproducts and also to identify areas of
      research to strengthen risk assessment for nanomaterials. The research roadmaps
      which were proposed in this study will be helpful to fill up the current gaps in
      knowledge relevant nano risk assessment. 

PMID- 24278593
TI  - Exploring Chemotherapy-Induced Toxicities through Multivariate Projection of Risk
      Factors: Prediction of Nausea and Vomiting.
AB  - Many risk factors exist for chemotherapy-induced nausea and vomiting (CINV). This
      study utilized a multivariate projection technique to identify which risk factors
      were predictive of CINV in clinical practice. A single-centre, prospective,
      observational study was conducted from January 2007~July 2010 in Singapore.
      Patients were on highly (HECs) and moderately emetogenic chemotherapies
      with/without radiotherapy. Patient demographics and CINV risk factors were
      documented. Daily recording of CINV events was done using a standardized diary.
      Principal component (PC) analysis was performed to identify which risk factors
      could differentiate patients with and without CINV. A total of 710 patients were
      recruited. Majority were females (67%) and Chinese (84%). Five risk factors were
      potential CINV predictors: histories of alcohol drinking, chemotherapy-induced
      nausea, chemotherapy-induced vomiting, fatigue and gender. Period (ex-/current
      drinkers) and frequency of drinking (social/chronic drinkers) differentiated the
      CINV endpoints in patients on HECs and anthracycline-based, and XELOX regimens,
      respectively. Fatigue interference and severity were predictive of CINV in
      anthracycline-based populations, while the former was predictive in HEC and XELOX
      populations. PC analysis is a potential technique in analyzing clinical
      population data, and can provide clinicians with an insight as to what predictors
      to look out for in the clinical assessment of CINV. We hope that our results will
      increase the awareness among clinician-scientists regarding the usefulness of
      this technique in the analysis of clinical data, so that appropriate preventive
      measures can be taken to improve patients' quality of life. 

PMID- 24278594
TI  - The association of heavy metal of blood and serum in the Alzheimer's diseases.
AB  - This study has attempted to establish an analysis method through validation
      against heavy metals in the body (Pb, Cd and Hg) using ICP-MS and Gold
      amalgamation and find out the relevance between heavy metal and Alzheimer's
      disease after analyzing the distribution of heavy metal concentration (Pb, Cd and
      Hg) and correlations between a control group and Alzheimer's disease group. In
      this study, Pb and Cd levels in the blood and serum were validation using ICP-MS.
      For analysis of Hg levels in the blood and serum, the gold amalgamation-based
      'Direct Mercury Analyzer' has been used. According to an analysis on the heavy
      metal concentration (Pb, Cd and Hg concentration) in the blood, Cd concentration
      was high in the Alzheimer's disease group. In the serum, on the contrary, Pb and
      Hg were high in the Alzheimer's disease group. For analysis of correlations
      between heavy metal levels in the blood and serum and Alzheimer's disease, t-test
      has been performed. Even though correlations were observed between the blood lead
      levels and Alzheimer's disease, they were statistically insignificant because the
      concentration was higher in a control group. No significance was found in Cd and
      Hg. In the serum, on the other hand, no statistical significance was found
      between the heavy metal (Pb, Cd and Hg) and Alzheimer's disease. In this study,
      no statistical significance was observed between heavy metal and decrease in
      cognitive intelligence. However, it appears that a further study needs to be
      performed because the results of the conventional studies were inconsistent. 

PMID- 24278595
TI  - Acute Dermal Toxicity Study of Bee Venom (Apis mellifera L.) in Rats.
AB  - Bee venom (Apis mellifera L. BV) has been used as a cosmetic ingredient for anti
      ageing, anti-inflammatory and antibacterial functions. The aim of this study was
      to evaluate the acute toxicity after a single dermal administration of BV, BV was
      administered to 2 groups of Sprague-Dawley (SD) male and female rats (5
      animals/group) at doses of 0 and 1,500 mg/kg body weight (BW). Mortality,
      clinical signs, body weight changes and gross findings were continually monitored
      for 15 days following the single dose. There were no unscheduled deaths in any
      groups during the study period. No BV related clinical signs and body weight
      changes were observed in any groups during the study period. There were no
      abnormal gross findings at necropsy on day 15 after the treatment. On the basis
      of the above results, it was concluded that there were no treatment-related
      effect on mortality, clinical signs, body weight changes and gross findings in SD
      rats treated with a single dermal dose of BV at dose of 1,500 mg/kg BW.
      Therefore, the approximate lethal dose of BV was considered to be over 1,500
      mg/kg/day for both sexes of rats. BV may provide a developmental basis for a
      cosmetic ingredient or external application for topical uses. 

PMID- 24278596
TI  - Outbreak of bioaerosols with continuous use of humidifier in apartment room.
AB  - The effect of continuous humidifier use on the bioaerosol concentration in an
      indoor environment was investigated. An ultrasonic humidifier was operated for 10
      hr per day for 15 days in an apartment room. During this time period, viable
      bioaerosol samples were taken using a single-stage Andersen sampler containing
      culture media plates for bacteria and fungi. The culture plates were then
      incubated at room temperature for 2~7 days depending on the media. The counts for
      the air sample plates were corrected for multiple impactions using the positive
      hole conversion method and are reported as the colony forming units per cubic
      meter of air (CFU/m(3)). While the bacterial concentration measured using the
      tryptic soy agar (TSA) did not show any significant change during the first 3
      days, the concentration increased from the 6(th) day (6979 CFU/m(3)) and reached
      a maximum on the 9(th) day (46431 CFU/m(3)). The concentration then decreased to
      2470 CFU/m(3) on the 12(th) day, at which point the fungal concentration
      increased rapidly to 14424~16038 CFU/m(3). Also, while the fungal concentration
      showed a significant change until the 9(th) day of humidifier use, fungal growth
      was observed on the wallpaper and increased rapidly from the 12(th) day. However,
      the bacterial concentration increased rapidly after the fungi were removed by
      remediation. The major fungal species identified in the samples were Penicillium
      representing 34%, Aspergillus representing 31%, Cladosporium representing 24%,
      and Alternaria representing 1%. The results also indicated that a relative
      humidity over 80% was easily achieved with continuous humidifier use. Yet,
      maintaining a high humidity in a room can cause a rapid outbreak of microbial
      growth. 

PMID- 24278597
TI  - Chlorination of ortho-position on Polychlorinated Biphenyls Increases Protein
      Kinase C Activity in Neuronal Cells.
AB  - Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental
      pollutants. Recently, it is suggested that neurotoxic effects such as motor
      dysfunction and impairment in memory and learning have been associated with PCB
      exposure. However, structure relationship of PCB congeners with neurotoxic
      effects remains unknown. Since PKC signaling pathway is implicated in the
      modulation of motor behavior as well as learning and memory and the role of PKC
      are subspecies-specific, we attempted to study the effects of structurally
      distinct PCBs on the total PKC activity as well as subspecies of PKC in
      cerebellar granule cell culture model. Cells were exposed to 0, 25 and 50 MUM of
      PCB-126, PCB-169, PCB-114, PCB-157, PCB-52 and PCB-4 for 15 min. Cells were
      subsequently analyzed by [(3)H] phorbol ester binding assay or immunoblotted
      against PKC-alpha and -epsilon monoclonal antibodies. While non-dioxin-like-PCB
      (PCB-52 and PCB-4) induced a translocation of PKC-alpha and -epsilon from cytosol
      to membrane fraction, dioxin-like PCBs (PCB-126, -169, -114, -157) had no
      effects. [(3)H] Phorbol ester binding assay also revealed structure-dependent
      increase similar to translocation of PKC isozymes. While PCB-4 induced
      translocation of PKC-alpha and -epsilon was inhibited by ROS inhibitor, the
      pattern of translocation was not affected in presence of AhR inhibitor. It is
      suggested that PCB-4-induced PKC activity may not be mediated via AhR-dependent
      pathway. Taken together, our findings suggest that chlorination of ortho-position
      in PCB may be a critical structural moiety associated with neurotoxic effects,
      which may be preferentially mediated via non-AhR-dependent pathway. Therefore,
      the present study may contribute to understanding the neurotoxic mechanism of
      PCBs as well as providing a basis for establishing a better neurotoxic
      assessment. 

PMID- 24278598
TI  - Human skin safety test of green tea cell extracts in condition of allergic
      contact dermatitis.
AB  - Various kinds of positive effects of green tea extracts had been studied for long
      time which included anti-inflammation, anti-aging, and cardiometabolic effects.
      Although topical steroid and non-steroidal calcineurin inhibitors may control
      clinical symptoms of allergic contact dermatitis, some of patients also present
      allergic reaction to these topical agents. Therefore, we have tried green tea
      extracts for managing this skin disorder with expectation of anti-inflammatory
      effect without potential side effects including skin irritation and toxic
      responses. The toxicity test of green tea extract also did not show any sign of
      irritation in the skin throughout the test period. Moderate severity of allergic
      contact dermatitis presented satisfactory clinical outcome at second week follow
      up which was final visit of outpatient. This result mean that green tea extract
      has a positive effect for managing allergic contact dermatitis but its potency
      and efficacy seem to be so not strong enough to control moderate severity allergy
      skin lesion. In this pilot study, we were able to conclude that green tea cell
      extracts might be applied for potential anti-inflammatory soaking without skin
      toxicity. 

PMID- 24278599
TI  - Increased Flavonoid Compounds from Fermented Houttuynia cordata using Isolated
      Six of Bacillus from Traditionally Fermented Houttuynia cordata.
AB  - Flavonoids, which form a major component in Houttuynia cordata Thunb., display a
      wide range of pharmacological activities. The expression of plant flavonoids is
      partly regulated by fermentation. Therefore, we studied the effects of
      fermentation on H. cordata in order to identify the strains present during the
      fermentation process, and to determine whether fermented H. cordata could be used
      as a probiotic. Our results showed that all 6 of the bacterial strains isolated
      from fermented H. cordata (FHC) belonged to the genus Bacillus. As expected,
      fermenting H cordata also increased the flavonoid content as increases were
      observed in the levels of rutin, quercitrin, and quercetin. To test the effects
      of fermentation, we treated LPS-stimulated RAW264.7 cells with non-fermented H.
      cordata extracts (HCE) or FHC extracts (FHCE). Compared to the HCE-treated cells,
      the FHCE-treated cells showed increased viability. No cytotoxic effects were
      detected in the FHCE-treated groups in the 2 cell lines used in the study,
      namely, RAW264.7 and RBL-2H3. FHCE-treated HepG2 cells showed decreased growth,
      compared to HCE-treated HepG2 cells. These results indicate that the fermented H.
      cordata predominantly contained Bacillus strains. Furthermore, FHCE are able to
      prevent LPS-induced inflammatory effects and inhibit the growth of HepG2 cells. 

PMID- 24278600
TI  - Diagnostic Assay of Toxic Zinc in an Ex vivo Cell Using Voltammetry.
AB  - Voltammetric detection of the toxic Zn ion was investigated using a fluorine
      doped graphite pencil electrode (FPE). It is notable from the study that pencils
      were used as reference and working electrodes. In all the experiments, a clean
      seawater electrolyte solution was used to yield good results. The analytical
      working range was attained to 10 MUgL(-1). The optimized voltammetric condition
      was examined to maximize the effect of the detection of trace Zn. The developed
      sensor was applied to an earthworm's tissue cell. It was found that the methods
      can be applicable to in vivo fluid or agriculture soil and plant science. 

PMID- 24278601
TI  - Derivation of Ecological Protective Concentration using the Probabilistic
      Ecological Risk Assessment applicable for Korean Water Environment: (I) Cadmium.
AB  - Probabilistic ecological risk assessment (PERA) for deriving ecological
      protective concentration (EPC) was previously suggested in USA, Australia, New
      Zealand, Canada, and Netherland. This study suggested the EPC of cadmium (Cd)
      based on the PERA to be suitable to Korean aquatic ecosystem. First, we collected
      reliable ecotoxicity data from reliable data without restriction and reliable
      data with restrictions. Next, we sorted the ecotoxicity data based on the site
      specific locations, exposure duration, and water hardness. To correct toxicity by
      the water hardness, EU's hardness corrected algorithm was used with slope factor
      0.89 and a benchmark of water hardness 100. EPC was calculated according to
      statistical extrapolation method (SEM), statistical extrapolation methodAcute to
      chronic ratio (SEMACR), and assessment factor method (AFM). As a result, aquatic
      toxicity data of Cd were collected from 43 acute toxicity data (4
      Actinopterygill, 29 Branchiopoda, 1 Polychaeta, 2 Bryozoa, 6 Chlorophyceae, 1
      Chanophyceae) and 40 chronic toxicity data (2 Actinopterygill, 23 Branchiopoda, 9
      Chlorophyceae, 6 Macrophytes). Because toxicity data of Cd belongs to 4 classes
      in taxonomical classification, acute and chronic EPC (11.07 MUg/l and 0.034
      MUg/l, respectively) was calculated according to SEM technique. These values were
      included in the range of international EPCs. This study would be useful to
      establish the ecological standard for the protection of aquatic ecosystem in
      Korea. 

PMID- 24278602
TI  - A transfer of silver nanoparticles from pregnant rat to offspring.
AB  - SILVER NANOPARTICLES (SIZE: 7.9 +/- 0.95 nm, dosage: 250 mg/kg) were orally
      administered to pregnant rats. At 4 days after parturition, four pups were
      randomly selected (one pup from one dam) and silver level in liver, kidney, lung
      and brain was determined by ICP-MS and electron microscope. As results, silver
      nanoparticles highly accumulated in the tissues of the pups. Silver level in the
      treated group was 132.4 +/- 43.9 ng/g in the kidney (12.3 fold compared to
      control group), 37.3 +/- 11.3 ng/g in the liver (7.9 fold), 42.0 +/- 8.6 ng/g in
      the lung (5.9 fold), and 31.1 +/- 4.3 ng/g in the brain (5.4 fold). This result
      suggested that the possible transfer of silver nanoparticles from pregnant dams
      to the fetus through mainly placenta.

PMID- 24278603
TI  - Heavy metal risk management: case analysis.
AB  - To prepare measures for practical policy utilization and the control of heavy
      metals, hazard control related institutions by country, present states of control
      by country, and present states of control by heavy metals were examined. Hazard
      control cases by heavy metals in various countries were compared and analyzed. In
      certain countries (e.g., the U.S., the U.K., and Japan), hazardous substances
      found in foods (e.g., arsenic, lead, cadmium, and mercury) are controlled. In
      addition, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) recommends
      calculating the provisional tolerable weekly intake (PTWI) of individual heavy
      metals instead of the acceptable daily intake (ADI) to compare their pollution
      levels considering their toxicity accumulated in the human body. In Korea,
      exposure assessments have been conducted, and in other countries, hazardous
      substances are controlled by various governing bodies. As such, in Korea and
      other countries, diverse food heavy metal monitoring and human body exposure
      assessments are conducted, and reducing measures are prepared accordingly. To
      reduce the danger of hazardous substances, many countries provide leaflets and
      guidelines, develop hazardous heavy metal intake recommendations, and take
      necessary actions. Hazard control case analyses can assist in securing consumer
      safety by establishing systematic and reliable hazard control methods. 

PMID- 24278604
TI  - Effects of Oxidized Tallow on the Rabbit Serum Lipids and Antioxidant Activity of
      the In-vitro Lipids.
AB  - This paper describes the effects of thermally oxidized tallow on the serum lipids
      profile and radical scavenging activity (RSA) of the lipids extracted from the
      different tissues of the rabbits. Tallow was thermally oxidized at 130C for 9,
      18, 27, 36 and 45 h respectively. Thermally oxidized tallow was fed to the local
      strain of Himalayan rabbits for one week. Results show that oxidation increases
      the formation of hydroperoxides and decrease the level of radical scavenging
      activity of the tallow. The rabbit serum lipids profile showed a dose dependent
      increase in triglyceride, total cholesterol and LDL-cholesterol. However, no
      statistically significant increase was observed in the HDL-cholesterol with an
      increase of oxidation time. Serum glucose and rabbits body weight decrease
      significantly (p < 0.05) and was highly correlated with the serum lipids profile.
      The percent RSA of the lipids extracted from the liver, brain and muscles tissues
      showed a significant decrease with respect to 0.5, 1.0 and 1.5 g/body weight as
      well as oxidation time. Data suggests that thermal oxidation and use of thermally
      oxidized beef tallow is harmful and therefore an alternative way of cooking
      should be used. 

PMID- 24278605
TI  - External Application of Fermented Olive Flounder (Paralichthys olivaceus) Oil
      Alleviates Inflammatory Responses in 2,4-Dinitrochlorobenzeneinduced Atopic
      Dermatitis Mouse Model.
AB  - Allergic skin inflammation such as atopic dermatitis (AD) is characterized by
      edema and infiltration with various inflammatory cells such as mast cells,
      basophils, eosinophils and T cells. Thymic stromal lymphopoietin (TSLP) is
      produced mainly by epidermal keratinocytes, as well as dermal fibroblasts and
      mast cells in the skin lesions of AD. Omega-3 polyunsaturated fatty acids in fish
      oil can reduce inflammation in allergic patients. Fermentation has a tremendous
      capacity to transform chemical structures. The antiinflammatory effects of fish
      oil have been described in many diseases, but the beneficial effects by which
      fermented olive flounder oil (FOF) modulates the allergic response is poorly
      understood. In this study, we produced FOF and tested its ability to suppress the
      various allergic inflammatory responses. The ability of FOF to modulate the
      immune system was investigated using a mouse model of AD. The FOF-treated group
      showed significantly decreased immunoglobulin E (IgE) and histamine in serum.
      Also, the increased TSLP expression was significantly inhibited in the FOF group;
      the FOF-treated group was not appreciably different from the hydrocort cream
      treatment group. In addition, FOF treatment resulted in a smaller spleen size
      with reduced the thickness and length compared to the induction group.
      Splenocytes from mice treated with FOF produced significantly less IFN-gamma, IL
      4, T-box transcription factor (T-bet) and GATA binding protein 3 (GATA3)
      expression compared with the induction group. These results suggest that FOF may
      be effective in treating the allergic symptoms of AD. 5. 

PMID- 24278606
TI  - Effects of White Radish (Raphanus sativus) Enzyme Extract on Hepatotoxicity.
AB  - Raphanus sativus (Cruciferaceae), commonly known as radish is widely available
      throughout the world. From antiquity it has been used in folk medicine as a
      natural drug against many toxicants. The present study was designed to evaluate
      the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE)
      in vitro and in vivo test. The IC50 values of REE in human liver derived HepG2
      cells was over 5,000 MUg/ml in tested maximum concentration. The effect of REE to
      protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay.
      REE showed their hepatoprotective activities on tacrineinduced cytotoxicity and
      the EC50 value was 1,250 MUg/ml. Silymarin, an antihepatotoxic agent used as a
      positive control exhibited 59.7% hepatoprotective activitiy at 100 MUg/ml.
      Moreover, we tested the effect of REE on carbon tetrachloride (CCl4)-induced
      liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of
      50 mg/kg were orally administered to CCl4-treated rats. The results showed that
      REE and silymarin significantly reduced the elevated levels of serum enzyme
      markers induced by CCl4. The biochemical data were supported by evaluation with
      liver histopathology. These findings suggest that REE, can significantly diminish
      hepatic damage by toxic agent such as tacrine or CCl4. 

PMID- 24278607
TI  - Human health risk assessment of trichloroethylene from industrial complex a.
AB  - This study investigated the human health risks of trichloroethylene from
      Industrial Complex A. The excessive carcinogenic risks for central tendency
      exposure were 1.40 * 10(?5) for male and female residents in the vicinity of
      Industrial Complex A. The excessive cancers risk for reasonable maximum exposure
      were 2.88 * 10(?5) and 1.97 * 10(?5) for males and females, respectively. These
      values indicate that there are potential cancer risks for exposure to these
      concentrations. The hazard index for central tendency exposure to
      trichloroethylene was 1.71 for male and female residents. The hazard indexes for
      reasonable maximum exposure were 3.27 and 2.41 for males and females,
      respectively. These values were over one, which is equivalent to the threshold
      value. This result showed that adverse cancer and non-cancer health effects may
      occur and that some risk management of trichloroethylene from Industrial Complex
      A was needed. 

PMID- 24278608
TI  - Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces
      sinclairii in Rats.
AB  - Paecilomyces sinclairiis (PS) is known as a functional food or human health
      supplement. However concerns have been raised about its kidney toxicity. This
      study was performed to investigate the kidney toxicity of PS by 13 week-oral
      administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney
      damage biomarkers including beta-2-microglobulin (beta2m), glutathione S
      transferase alpha (GST-alpha), kidney injury molecule 1 (KIM-1), tissue inhibitor
      of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor
      (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated
      lipocalin (NGAL) and osteopontin were measured during or after the treatment of
      PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS.
      However, kidney cell karyomegaly and tubular hypertrophy were observed dose
      dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in
      kidney and urine were increased dose dependently in male or at the highest dose
      in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks
      of post-exposure in both genders. Cystatin C in kidney was decreased at all
      treatment groups but inversely increased in urine. The changes in kidney damage
      biomarkers were more remarkable in male than female rats. These data indicate
      that the PS may provoke renal cell damage and glomerular filtration dysfunction
      in rats with histopathological lesions and change of kidney damage biomarkers in
      kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked
      indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers
      in serum were not influenced. 

PMID- 24278609
TI  - A study on hazard assessment of employees in new buildings.
AB  - In order to evaluate the physical and psychological health effects of air
      pollutants from new building materials, 100 employees who worked in new buildings
      were given a general health questionnaire, and the prevalence of their subjective
      complaints was measured. The collected data were classified according to age,
      gender, smoking status, profession, working time, sleep time, life style, and
      length of employment. The results obtained were summarized as follows: The THI
      lie scale scores were significantly higher among the older respondents. Compared
      to males, females showed a significantly higher level in the depression itemas
      well asa tendency toward high ratios of physical and psychological complaints.
      The smoking group showed higher scores regarding health complaints related to
      most physical and psychological items. Smokers showed significantly increased
      respiratory organ complaints compared to nonsmokers. Those with a profession
      showed significantly higher level of nervousness. The group of those working 7 to
      10 hours group showed higher rates of complaints in the multiple subjective
      symptoms and mouth/anus items than the group working less than 2 hours. Those
      living an irregular life showed a tendency toward higher rates of complaints for
      most physical and psychological subjective factors. Those who were satisfied with
      their environments showed significantly lower scores in the mouth/anus,
      impulsiveness, mental irritability, depression, and nervousness items. In
      summary, this study shows that the health complaint scores regarding physical and
      psychological symptoms tended to be higher among the unsatisfied group, the
      irregular life group, the group who worked long hours, the elderly, smokers, and
      females. These results can be used to improve the psychosomatic health status and
      working environments of employees working in new buildings. 

PMID- 24278610
TI  - Cyanide poisoning deaths detected at the national forensic service headquarters
      in seoul of Korea: a six year survey (2005~2010).
AB  - The records of 255 cyanide poisoning deaths obtained from National Forensic
      Service (NFS) headquarters, located in Seoul of Korea, from 2005 to 2010 were
      retrospectively reviewed. The mean age was 41.88 +/- 13.09 and range was 6~80
      years (unknown in seven cases). The number of deaths of males and females were
      200 and 53, respectively (unknown in two cases). The largest number of cases
      occurred in people aged 40-49 years (81 cases, 31.8%), followed by the age groups
      30~39 years (51 cases, 20%), 50~59 years (44 cases, 17.2%) and 20~29 years (43
      cases, 16.9%). The total number of deaths among other age groups (below 10,
      10~19, 60~69, 70~79, over 80 years and unknown) were 36, representing only 14.1%.
      Of all cyanide poisoning deaths, 97.3% were due to suicide, and 14.5% of the
      total number who died received medical treatment. The most frequent site for
      ingestion was the person's own residence (120 cases, 47.1%) and the route of
      administration was mainly oral (252, 98.8%). From the total of 255 cyanide
      poisoning cases, white powders were submitted for analysis in 92 cases. Potassium
      cyanide and sodium cyanide occupied 51 and 41 cases, respectively. This study
      showed that poisoning deaths due to cyanide are one of the continuously reported
      public health problems in Korea. Enforcement of regulations and safety education
      to prevent cyanide poisoning should be carried out by the government. 

PMID- 24278611
TI  - A Study on Health Hazards to Employees near Main Streets.
AB  - In order to evaluate the physical and psychological health effects from
      automobile air pollution, 99 employees who worked near a main street were given a
      general health questionnaire, and the prevalence of their subjective complaints
      was measured. The collected data were classified according to gender, sleep time,
      degree of regular exercise, self-consciousness of symptoms, length of employment,
      work time, rest time, and smoking status. The results obtained were summarized as
      follows: The scores related to health complaints regarding physical and
      psychological items were higher in females than in males. THI scores were higher
      for the < 4 hour sleep time group. The health complaint scores for physical items
      were higher in the regular exercise group, whereas most scores for mental items
      were higher in the irregular exercise groups. The health complaints scores for
      physical and psychological items were higher in the unhealthy symptom group than
      in other groups. Those employees who had worked for > 4 years showed
      significantly higher rates of complaints regarding the eyes and skin. THI scores
      were higher for the < 6 hour working time group. The smoking group showed higher
      scores regarding health complaints related to physical items. The THI scores of
      the respiratory organs, mouth, anus, and digestive organs were significantly
      higher for the smoking group than for the non-smoking group. In summary, this
      study shows that the health complaint scores regarding physical and psychological
      symptoms tended to be higher among the unhealthy group, the less sleep time
      group, the less work time group, smokers, and females. These results can be used
      to improve the psychosomatic health status and working environments of employees
      who work near a main street. 

PMID- 24278612
TI  - Biocompatible dispersion methods for carbon black.
AB  - The biological activity of particles is largely dependent on their size in
      biological systems. Dispersion in the aqueous phase has been both a critical
      impediment to and a prerequisite for particle studies. Carbon black has been used
      as a surrogate to investigate the biological effects of carbonaceous particles.
      Here, biocompatible methods were established to disperse carbon black into
      ultrafine and fine particles which are generally distinguished by the small size
      of 100 nm. Carbon black with a distinct particle size, N330 and N990 were
      suspended in blood plasma, cell culture media, Krebs-Ringer's solution (KR), or
      physiological salt solution (PSS). Large clumps were observed in all dispersion
      preparations; however, sonication improved dispersion - averaged particle sizes
      for N330 and N990 were 85.0 +/- 42.9 and 112.4 +/- 67.9 nm, respectively, in
      plasma; the corresponding sizes in culture media were 84.8 +/- 38.4 and 164.1 +/-
      77.8 nm. However, sonication was not enough to disperse N330 less than 100 nm in
      either KR or PSS. Application of Tween 80 along with sonication reduced the size
      of N330 to less than 100 nm, and dispersed N990 larger than 100 nm (73.6 +/- 28.8
      and 80.1 +/- 30.0 nm for N330 and 349.5 +/- 161.8 and 399.8 +/- 181.1 nm for N990
      in KR and PSS, respectively). In contrast, 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) exhibited little effect. Electron microscopy confirmed the
      typical aciniform structure of the carbon arrays; however, zeta potential
      measurement failed to explain the dispersibility of carbon black. The methods
      established in this study could disperse carbon black into ultrafine and fine
      particles, and may serve as a useful model for the study of particle toxicity,
      particularly size-related effects. 

PMID- 24278613
TI  - Nasal and pulmonary toxicity of titanium dioxide nanoparticles in rats.
AB  - In recent decades, titanium dioxide (TiO2) nanoparticles have been used in
      various applications, including paints, coatings, and food. However, data are
      lacking on the toxicological aspects associated with their use. The aim of this
      study was to assess the inhalation toxicity of TiO2 nanoparticles in rats by
      using inhalation exposure. Male Wistar rats were exposed to TiO2 nanoparticles
      for 2 weeks (6 hr/day, 5 days/week) at a mean mass concentration of 11.39 +/-
      0.31 mg/m(3). We performed time-course necropsies at 1, 7, and 15 days after
      exposure. Lung inflammation and injury were assessed on the basis of the total
      and individual cell counts in bronchoalveolar lavage fluid (BALF), and by
      biochemical assays, including an assay for lactate dehydrogenase (LDH).
      Furthermore, histopathological examination was performed to investigate the lungs
      and nasal cavity of rats. There were no statistically significant changes in the
      number of BALF cells, results of biochemical assays of BALF and serum, and
      results of cytokine analysis. However, we did observe histopathological changes
      in the nasal cavity tissue. Lesions were observed at post-exposure days 1 and 7,
      which resolved at post-exposure day 15. We also calculated the actual amounts of
      TiO2 nanoparticles inhaled by the rats. The results showed that the degree of
      toxicity induced by TiO2 nanoparticles correlated with the delivered quantities.
      In particular, exposure to small particles with a size of approximately 20 nm
      resulted in toxicity, even if the total particle number was relatively low. 

PMID- 24278615
TI  - Biodistribution of (99m)tc tricarbonyl glycine oligomers.
AB  - (99m)Tc tricarbonyl glycine monomers, trimers, and pentamers were synthesized and
      evaluated for their radiolabeling and in vivo distribution characteristics. We
      synthesized a (99m)Tc-tricarbonyl precursor with a low oxidation state (I).
      (99m)Tc(CO)3(H2O)3 (+) was then made to react with monomeric and oligomeric
      glycine for the development of bifunctional chelating sequences for biomolecules.
      Labeling yields of (99m)Tc-tricarbonyl glycine monomers and oligomers were
      checked by high-performance liquid chromatography. The labeling yields of (99m)Tc
      tricarbonyl glycine and glycine oligomers were more than 95%. We evaluated the
      characteristics of (99m)Tc-tricarbonyl glycine oligomers by carrying out a
      lipophilicity test and an imaging study. The octanol-water partition coefficient
      of (99m)Tc tricarbonyl glycine oligomers indicated hydrophilic properties. Single
      photon emission computed tomography imaging of (99m)Tc-tricarbonyl glycine
      oligomers showed rapid renal excretion through the kidneys with a low uptake in
      the liver, especially of (99m)Tc tricarbonyl triglycine. Furthermore, we verified
      that the addition of triglycine to prototype biomolecules (AGRGDS and RRPYIL)
      results in the improvement of radiolabeling yield. From these results, we
      conclude that triglycine has good characteristics for use as a bifunctional
      chelating sequence for a (99m)Tc-tricarbonyl- based biomolecular imaging probe. 

PMID- 24278614
TI  - A 6-week oral toxicity study of oral cholera vaccine in sprague-dawley rats.
AB  - The present study was carried out to examine the toxicity and target organs of
      oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley
      rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated
      oral cholera vaccine that contains Vibrio cholerae and confers protection against
      cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139
      (strain 4260B). The animals were orally administered either OCV placebo (negative
      control) or OCV at a dose equivalent to 240 times the anticipated human dose.
      Throughout the administration period, no significant change was detected in
      clinical signs, body weight, food or water consumption, urinalysis results,
      hematological and clinical biochemistry test results, organ weights, necropsy, or
      histopathological examination results. Minor changes were found in hematological
      and clinical biochemistry tests; however, these changes were within normal
      ranges. The above results suggest that oral administration of OCV in rats did not
      induce any toxicologically meaningful changes, and the target organs could not be
      determined. This study was conducted in accordance with the guidelines
      established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and
      the OECD Principles of Good Laboratory Practice (1997). 

PMID- 24278616
TI  - Effect of Microalgal Extracts of Tetraselmis suecica against UVB-Induced
      Photoaging in Human Skin Fibroblasts.
AB  - Exposure of cells to ultraviolet B (UVB) radiation can induce production of free
      radicals and reactive oxygen species (ROS), which damage cellular components. In
      addition, these agents can stimulate the expression of matrix metalloproteinase
      (MMP) and decrease collagen synthesis in human skin cells. In this study, we
      examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W
      TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl
      (DPPH) and peroxyl radicals, followed by superoxide anions from the
      xanthine/xanthine oxidase system. We observed that the levels of both
      intracellular ROS and lipid peroxidation significantly increased in UVB
      irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic
      antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic
      antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS
      pretreatment, at the maximum tested concentration, significantly decreased
      intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide
      dismutase and glutathione levels in the cells. At this same concentration, W-TS
      did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified
      using RT-PCR techniques. The results showed that W-TS protected type 1
      procollagen against UVBinduced depletion in fibroblast cells in a dose-dependent
      manner via inhibition of UVB-induced MMP-1. Taken together, the results of the
      study suggest that W-TS effectively inhibits UVB-induced photoaging in skin
      fibroblasts by its strong anti-oxidant ability. 

PMID- 24278617
TI  - Anti-inflammatory Effect of Bumblebee Alcohol Extracts in CFA-Induced Rat Edema.
AB  - In this study, we prepared alcohol extracts of the larva, pupa, queen, and cocoon
      (clony) of B. ignitus, B. terrestris, and B. h. sapporoensis, and tested the anti
      inflammatory activity of the extracts by using a rat model of adjuvant-induced
      edema. The extracts derived from the queen of B. ignitus, the queen of B.
      terrestris, and the cocoon of B. ignitus decreased hind paw edema after 1 day of
      i.p. administration. These extracts also induced vasorelaxation and NO production
      in calf pulmonary artery endothelial cells. These results suggest that bumblebee
      alcohol extracts has anti-inflammatory and vasorelaxant properties. 

PMID- 24278618
TI  - The Chloroform Fraction of Carpinus tschonoskii Leaves Inhibits the Production of
      Inflammatory Mediators in HaCaT Keratinocytes and RAW264.7 Macrophages.
AB  - Inflammation is the immune system's response to infection and injury-related
      disorders, and is related to pro-inflammatory factors (NO, PGE2, cytokines, etc.)
      produced by inflammatory cells. Atopic dermatitis (AD) is a representative
      inflammatory skin disease that is characterized by increasing serum levels of
      inflammatory chemokines, including macrophage-derived chemokine (MDC). Carpinus
      tschonoskii is a member of the genus Carpinus. We investigated the anti
      inflammatory activity of C. tschonoskii by studying the effects of various
      solvent fractions prepared from its leaves on inflammatory mediators in HaCaT and
      RAW264.7 cells. We found that the chloroform fraction of C. tschonoskii inhibited
      MDC at both the protein and mRNA levels in HaCaT cells, acting via the inhibition
      of STAT1 in the IFN-gamma signaling pathway. In addition, the chloroform fraction
      significantly suppressed the expression of inflammatory factors induced by
      lipopolysaccharide stimulation, except COX-2 and TNF-alpha. These results suggest
      that the chloroform fraction of C. tschonoskii leaves may include a component
      with potential anti-inflammatory activity. 

PMID- 24278619
TI  - Single-dose oral toxicity of fermented scutellariae radix extract in rats and
      dogs.
AB  - The aim of this study was to investigate the acute oral toxicity of fermented
      Scutellariae Radix (JKTMHGu- 100) in rats and dogs. JKTM-HGu-100 was orally
      administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating
      single-dose oral toxicity test in beagle dogs was performed at doses of 500,
      1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body
      weight, mortality, and necropsy findings were examined for 2 weeks following oral
      administration. No toxicological changes related to the test substance nor
      mortality was observed after administration of a single oral dose of JKTM-HGu-100
      in rats or dogs. Therefore, the approximate lethal dose (LD) for oral
      administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and
      the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be
      over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in
      rodents or non-rodents at doses of 2,000 mg/kg or less. 

PMID- 24278620
TI  - The effects of hazardous chemical exposure on cardiovascular disease in chemical
      products manufacturing workers.
AB  - The purpose of this study was to understand the mechanism of cardiovascular
      disease (CVD) caused by exposure to hazardous chemicals. We investigated changes
      in the symptoms of metabolic syndrome, which is strongly related to CVD, and in
      levels of other CVD risk factors, with a special emphasis on the roles of
      catecholamines and oxidative stress. The results revealed that neither body mass
      index (BMI) nor waist and hip circumferences were associated with exposure to
      hazardous chemicals. Among metabolic syndrome criteria, only HDL-cholesterol
      level increased on exposure to hazardous chemicals. Levels of epinephrine (EP)
      and norepinephrine (NEP) were not influenced by exposure to hazardous chemicals;
      however, the total antioxidative capacity (TAC) reduced because of increased
      oxidative stress. Both hazardous chemical exposure level and metabolite excretion
      were related to EP, NEP, and the oxidative stress index (OSI). Logistic
      regression analysis with these factors as independent variables and metabolic
      syndrome criteria as dependent variables revealed that EP was associated with
      blood pressure, and NEP with metabolic syndrome in the chemicalexposed group. In
      conclusion, the results suggest that reactive oxygen species generated and
      oxidative stress due to exposure to hazardous chemicals act as mediators and
      cause changes in the physiological levels of EP and NEP to increase blood
      pressure. This ultimately leads to the development of CVD through increase in
      cholesterol, triglyceride, and blood glucose levels by lipid peroxidation. 

PMID- 24278621
TI  - Zearalenone affects immune-related parameters in lymphoid organs and serum of
      rats vaccinated with porcine parvovirus vaccine.
AB  - Rats were administered zearalenone (ZEA) via gavage at dosages of 0, 1, 5, and 30
      mg/kg for 36 days. On treatment day 8, inactivated porcine parvovirus vaccine
      (Vac) was injected intraperitoneally. Antibody production against porcine
      parvovirus was then measured as a function of ZEA treatment. Compared to the
      vaccine alone, ZEA treatment, with or without Vac, decreased the serum level of
      IgG. The level of IgM decreased in all ZEA groups at day 22, but the decrease was
      sustained only in the medium-dose ZEA group at day 36. The level of IgA was
      unchanged in the Vac only and ZEA groups at day 22, but was decreased in the 5
      mg/kg ZEA plus Vac group compared to the Vac only group at day 36. The level of
      IgE was decreased by all doses of ZEA at day 22, but was unaffected in ZEA plus
      Vac groups compared to the Vac only group. The levels of IL-1 in the thymus and
      spleen; INF-gamma in serum; IL-2, IL-6, and IL-10 in the thymus; and IL-10 and
      IFN-gamma in the spleen decreased after ZEA administration. Furthermore, the
      levels of IL-1beta in the spleen and mesenteric lymph node, IL-1beta in the
      thymus, IL-2 in the thymus and spleen, IL-6 in the thymus, IL-10 and IFN-gamma in
      the spleen, and GM-CSF and TNF-alpha in the thymus decreased after vaccination in
      rats exposed to ZEA. In conclusion, these results suggest that ZEA exposure via
      drinking water can cause an immunosuppressive effect by decreasing
      immunoglobulins in serum and cytokines in lymphoid organs. 

PMID- 24278622
TI  - MicroSPECT and MicroPET Imaging of Small Animals for Drug Development.
AB  - The process of drug discovery and development requires substantial resources and
      time. The drug industry has tried to reduce costs by conducting appropriate
      animal studies together with molecular biological and genetic analyses. Basic
      science research has been limited to in vitro studies of cellular processes and
      ex vivo tissue examination using suitable animal models of disease. However, in
      the past two decades new technologies have been developed that permit the imaging
      of live animals using radiotracer emission, Xrays, magnetic resonance signals,
      fluorescence, and bioluminescence. The main objective of this review is to
      provide an overview of small animal molecular imaging, with a focus on nuclear
      imaging (single photon emission computed tomography and positron emission
      tomography). These technologies permit visualization of toxicodynamics as well as
      toxicity to specific organs by directly monitoring drug accumulation and
      assessing physiological and/or molecular alterations. Nuclear imaging technology
      has great potential for improving the efficiency of the drug development process.

PMID- 24278623
TI  - Betaine Alleviates Hypertriglycemia and Tau Hyperphosphorylation in db/db Mice.
AB  - Betaine supplementation has been shown to alleviate altered glucose and lipid
      metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated
      the beneficial effects of betaine in diabetic db/db mice. Alleviation of
      endoplasmic reticulum (ER) and oxidative stress was also examined in the livers
      and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db
      mice were fed with or without 1% betaine for 5 wk (referred to as the db/db
      betaine group and the db/db group, respectively). Lean non-diabetic db/db+ mice
      were used as the control group. Betaine supplementation significantly alleviated
      hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome
      proliferator-activated receptor gamma coactivator 1 alpha, a major transcription
      factor involved in gluconeogenesis. Lower serum triglyceride concentrations were
      also observed in the db/db-betaine group compared to the db/db group. Betaine
      supplementation induced hepatic peroxisome proliferator-activated receptor alpha
      and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA
      carboxylase activity. Mice fed a betaine-supplemented diet had increased total
      glutathione concentrations and catalase activity, and reduced lipid peroxidation
      levels in the liver. Furthermore, betaine also reduced ER stress in liver and
      brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were
      lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our
      findings suggest that betaine improves hyperlipidemia and tau
      hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and
      oxidative stress. 

PMID- 24278624
TI  - Antihyperglycemic and Antihyperlipidemic Effects of Fermented Rhynchosia
      nulubilis in Alloxan-induced Diabetic Rats.
AB  - Alloxan administration in rats is used as a model for non-insulin dependent
      diabetes mellitus (NIDDM). NIDDM is a multifactorial disease, characterized by
      hyperglycemia and lipoprotein abnormalities. In this study, we evaluated the
      antihyperglycemic and antihyperlipidemic effects of fermented Rhynchosia
      nulubilis (FRN) through the regulation of glucose uptake in alloxan-induced rats.
      Fermented R. nulubilis was administered orally for 28 d at 500 mg/kg of body
      weight. Body weight and food intake were monitored every day. Biochemical
      parameters were quantified after 4 week. In the diabetic + FRN group, body weight
      increased significantly and blood glucose concentrations decreased when compared
      to those of the diabetic group. After 2 hr of administration, the oral glucose
      tolerance test (OGTT) indicated a significant reduction in the diabetic + FRN
      group compared to diabetic group. The diabetic + FRN group experienced a
      significant reduction in total cholesterol, triglycerides, low density
      lipoprotein, coronary risk factors, and malondialdehyde concentrations, with
      significantly increased high density lipoprotein compared to those of diabetic
      group. These results demonstrate that fermented R. nulubilis possesses potent
      antihyperglycemic and antihyperlipidemic activity in alloxan-induced diabetic
      rats. 

PMID- 24278625
TI  - Biodistribution of (99m)tc labeled integrin antagonist.
AB  - The selective targeting of an integrin alphavbeta3 receptor using radioligands
      may enable the assessment of angiogenesis and integrin alphavbeta3 receptor
      status in tumors. The aim of this research was to label a peptidomimetic integrin
      alphavbeta3 antagonist (PIA) with (99m)Tc(CO)3 and to test its receptor targeting
      properties in nude mice bearing receptor-positive tumors. PIA was reacted with
      tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product,
      PIA-aminodiacetic acid (ADA), was radiolabeled with [(99m)Tc(CO)3(H2O)3](+1), and
      purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion
      exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical
      purity of (99m)Tc(CO)3-ADA-PIA (retention time, 10.5 min) was confirmed to be >
      95%. Biodistribution analysis was performed in nude mice (n = 5 per time point)
      bearing receptor-positive M21 human melanoma xenografts. The mice were
      administered (99m)Tc(CO)3-ADA-PIA intravenously. The animals were euthanized at
      0.33, 1, and 2 hr after injection for the biodistribution study. A separate group
      of mice were also co-injected with 200 MUg of PIA and euthanized at 1 hr to
      quantify tumor uptake. (99m)Tc(CO)3-ADA-PIA was stable in phosphate buffer for 21
      hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine,
      respectively. In tumor bearing mice, (99m)Tc(CO)3-ADA-PIA accumulated rapidly in
      a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from
      blood occurring primarily through the hepatobiliary system. At 20 min, the tumor
      toblood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g,
      but decreased to 0.12% ID/g when co-injected with an excess amount of PIA,
      indicating that accumulation was receptor mediated. These results demonstrate
      successful (99m)Tc labeling of a peptidomimetic integrin antagonist that
      accumulated in a tumor via receptor-specific binding. However, tumor uptake was
      very low because of low blood concentrations that likely resulted from rapid
      uptake of the agent into the hepatobiliary system. This study suggests that for
      (99m)Tc(CO)3-ADA-PIA to be useful as a tumor detection agent, it will be
      necessary to improve receptor binding affinity and increase the hydrophilicity of
      the product to minimize rapid hepatobiliary uptake. 

PMID- 24278626
TI  - Embryotoxicity and toxicokinetics of the antimalarial artesunate in rats.
AB  - This study was conducted to investigate the potential embryo-fetal toxicity and
      toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley
      rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via
      oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The
      fetuses were examined for external, visceral, and skeletal abnormalities on
      gestational day 20. With regard to the dams, there were no deaths, treatment
      related clinical signs, changes in body weight, or food intake in any of the
      treatment groups. There were no treatment-related gross findings at necropsy in
      any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine
      weight and in the weight of female fetuses. There was also an increase in fetal
      deaths (primarily late resorptions) and an increase in post-implantation losses
      (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal
      variations at 4 and 8 mg/kg was observed. These defects included minor changes in
      the appearance of the kidney and thymus, as well as absent ribs or thoracic
      vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated
      females per group. Using liquid chromatography-mass spectrometry (LC-MS)
      analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA)
      were quantified in plasma from rats on gestational days 5, 6, 10, and 15.
      Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was
      evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma,
      since ARTS could not be consistently detected in plasma at the three doses
      tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15,
      indicating limited placental transfer of the two agents. The embryofetal no
      observable-adverse-effect level (NOAEL) of the test item was considered to be 8
      mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development. 

PMID- 24278627
TI  - Selective Effects of Curcumin on CdSe/ZnS Quantum-dot-induced Phototoxicity Using
      UVA Irradiation in Normal Human Lymphocytes and Leukemia Cells.
AB  - Quantum dots (QDs) have received considerable attention due to their potential
      role in photosensitization during photodynamic therapy. Although QDS are
      attractive nanomaterials due to their novel and unique physicochemical
      properties, concerns about their toxicity remain. We suggest a combination
      strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from
      turmeric, to reduce QD-induced cytotoxicity. The aim of this study was to explore
      a potentially effective cancer treatment: co-exposure of HL-60 cells and human
      normal lymphocytes to CdSe/ZnS QDs and curcumin. Cell viability, apoptosis,
      reactive oxygen species (ROS) generation, and DNA damage induced by QDs and/or
      curcumin with or without ultraviolet A (UVA) irradiation were evaluated in both
      HL-60 cells and normal lymphocytes. In HL-60 cells, cell death, apoptosis, ROS
      generation, and single/double DNA strand breaks induced by QDs were enhanced by
      treatment with curcumin and UVA irradiation. The protective effects of curcumin
      on cell viability, apoptosis, and ROS generation were observed in normal
      lymphocytes, but not leukemia cells. These results demonstrated that treatment
      with QD combined with curcumin increased cell death in HL-60 cells, which was
      mediated by ROS generation. However, curcumin acted as an antioxidant in cultured
      human normal lymphocytes. 

PMID- 24278628
TI  - Evaluation of Oxidative DNA Damage Using an Alkaline Single Cell Gel
      Electrophoresis (SCGE) Comet Assay, and the Protective Effects of N
      Acetylcysteine Amide on Zearalenone-induced Cytotoxicity in Chang Liver Cells.
AB  - Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several
      species of Fusarium that are found in cereals and agricultural products. ZEN has
      been implicated in mycotoxicosis in farm animals and in humans. The toxic effects
      of ZEN are well known, but the ability of an alkaline Comet assay to assess ZEN
      induced oxidative DNA damage in Chang liver cells has not been established. The
      first aim of this study was to evaluate the Comet assay for the determination of
      cytotoxicity and extent of DNA damage induced by ZEN toxin, and the second aim
      was to investigate the ability of N-acetylcysteine amide (NACA) to protect cells
      from ZEN-induced toxicity. In the Comet assay, DNA damage was assessed by
      quantifying the tail extent moment (TEM; arbitrary unit) and tail length (TL;
      arbitrary unit), which are used as indicators of DNA strand breaks in SCGE. The
      cytotoxic effects of ZEN in Chang liver cells were mediated by inhibition of cell
      proliferation and induction of oxidative DNA damage. Increasing the concentration
      of ZEN increased the extent of DNA damage. The extent of DNA migration, and
      percentage of cells with tails were significantly increased in a concentration
      dependent manner following treatment with ZEN toxin (p < 0.05). Treatment with a
      low concentration of ZEN toxin (25 MUM) induced a relatively low level of DNA
      damage, compared to treatment of cells with a high concentration of ZEN toxin
      (250 MUM). Oxidative DNA damage appeared to be a key determinant of ZEN-induced
      toxicity in Chang liver cells. Significant reductions in cytolethality and
      oxidative DNA damage were observed when cells were pretreated with NACA prior to
      exposure to any concentration of ZEN. Our data suggest that ZEN induces DNA
      damage in Chang liver cells, and that the antioxidant activity of NACA may
      contribute to the reduction of ZEN-induced DNA damage and cytotoxicity via
      elimination of oxidative stress. 

PMID- 24278629
TI  - Milk transfer and toxicokinetics of valproic Acid in lactating cynomolgus
      monkeys.
AB  - Studies on milk transfer of drugs in non-human primates (NHPs) are among the
      crucial components in the assessment of peri- and postnatal toxicity because of
      the similarity between NHPs and humans. To evaluate the milk transfer of valproic
      acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were
      studied in pregnant cynomolgus monkeys. VPA was administered once daily to
      pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage
      from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations
      of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140,
      and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and
      milk on LDs 30 and 31, respectively, were quantified using liquid chromatography
      tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose
      of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA
      were generally quantifiable in the plasma of all treatment groups up to 24 hr
      after administration, which showed that VPA was absorbed and that the monkeys
      were systemically exposed to VPA and 4-ene-VPA. After administration of multiple
      doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk
      taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via
      milk, and the pup was exposed to VPA. Further, the concentration of VPA in the
      milk increased with an increase in the dose. Extremely low concentrations of 4
      ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant
      monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at
      doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via
      milk, and the VPA exposure to the pup increased with an increase in the dose of
      VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (<
      0.5 MUg/ml) in the milk and in the pup plasma. In this study, we established
      methods to confirm milk transfer in NHPs, such as mating and diagnosis of
      pregnancy by examining gestational sac with ultrasonography, collection of milk
      and pup plasma and determination of toxicokinetics, using cynomolgus monkeys. 

PMID- 24278630
TI  - Protective Effects of Houttuynia cordata Thunb. on Gentamicin-induced Oxidative
      Stress and Nephrotoxicity in Rats.
AB  - Development of a therapy providing protection from, or reversing gentamicin
      sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great
      clinical significance. The present study was designed to investigate the
      protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate
      induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into
      4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d,
      intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d,
      oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration).
      Treatments were administered once daily for 12 d. After 12 d, biochemical and
      histopathological analyses were conducted to evaluate oxidative stress and renal
      nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea
      nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide
      dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant
      activity. Animals treated with GS alone showed a significant increase in serum
      levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and
      CAT. Treatment of rats with HC showed significant improvement in renal function,
      presumably as a result of decreased biochemical indices and oxidative stress
      parameters associated with GS-induced nephrotoxicity. Histopathological
      examination of the rat kidneys confirmed these observations. Therefore, the novel
      natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative
      stress in rats. 

PMID- 24278631
TI  - Health Risks to Children and Adults Residing in Riverine Environments where
      Surficial Sediments Contain Metals Generated by Active Gold Mining in Ghana.
AB  - The purpose of this study was to investigate the current status of metal
      pollution in the sediment from rivers, lakes, and streams in active gold mining
      districts in Ghana. Two hundred and fifty surface sediment samples from 99
      locations were collected and analyzed for concentrations of As, Hg, Cr, Co, Cu,
      Fe, Zn, Pb, Cd, Ni, and Mn using inductively coupled plasma-mass spectroscopy
      (ICP-MS). Metal concentrations were then used to assess the human health risks to
      resident children and adults in central tendency exposure (CTE) and reasonable
      maximum exposure (RME) scenarios. The concentrations of Pb, Cd, and As were
      almost twice the threshold values established by the Hong Kong Interim Sediment
      Quality Guidelines (ISQG). Hg, Cu, and Cr concentrations in sediment were 14, 20,
      and 26 times higher than the Canadian Freshwater Sediment Guidelines for these
      elements. Also, the concentrations of Pb, Cu, Cr, and Hg were 3, 11, 12, and 16
      times more than the Australian and New Zealand Environment and Conservation
      Council (ANZECC) sediment guideline values. The results of the human health risk
      assessment indicate that for ingestion of sediment under the central tendency
      exposure (CTE) scenario, the cancer risks for child and adult residents from
      exposure to As were 4.18 * 10(-6) and 1.84 * 10(-7), respectively. This suggests
      that up to 4 children out of one million equally exposed children would contract
      cancer if exposed continuously to As over 70 years (the assumed lifetime). The
      hazard index for child residents following exposure to Cr(VI) in the RME scenario
      was 4.2. This is greater than the United States Environmental Protection Agency
      (USEPA) threshold of 1, indicating that adverse health effects to children from
      exposure to Cr(VI) are possible. This study demonstrates the urgent need to
      control industrial emissions and the severe heavy metal pollution in gold mining
      environments. 

PMID- 24278632
TI  - Post-translational modification of proteins in toxicological research: focus on
      lysine acylation.
AB  - Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling
      protein quantification in biofluids and tissues, thus taking toxicological
      research to the next level. Post-translational modification (PTM) alters the
      three-dimensional (3D) structure of proteins by covalently binding small
      molecules to them and therefore represents a major protein function
      diversification mechanism. Because of the crucial roles PTM plays in biological
      systems, the identification of novel PTMs and study of the role of PTMs are
      gaining much attention in proteomics research. Of the 300 known PTMs, protein
      acylation, including lysine formylation, acetylation, propionylation,
      butyrylation, malonylation, succinylation, and crotonylation, regulates the
      crucial functions of many eukaryotic proteins involved in cellular metabolism,
      cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent
      studies regarding novel types of lysine acylation, their biological functions,
      and their applicationsin toxicoproteomics research. 

PMID- 24278633
TI  - Safety evaluation of topical valproate application.
AB  - The potential role of topical valproate (VPA) in hair regrowth has been recently
      suggested. However, safety reports of VPA as a topical formulation are lacking.
      Therefore, in the present study, we investigated whether VPA causes skin
      irritation in humans. We first performed a cell viability test and showed that
      VPA did not exhibit toxicity toward HaCaT keratinocytes, fibroblasts, and RBL-3H
      mast cells. We then performed clinical patch test and skin irritation test
      through transdermal drug delivery with the help of microneedle rollers. No
      significant findings were obtained in the clinical patch test. In the skin
      irritation test, only 1 patient showed erythema at 1 hr, but the irritation
      reaction faded away within a few hours. Erythema and edema were not observed at
      24 hr. We concluded that VPA has minimal potential to elicit skin irritation.
      Therefore, we consider that VPA can safely be applied to human skin. 

PMID- 24278634
TI  - Single oral dose toxicity study of prebrewed armeniacae semen in rats.
AB  - Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as
      it contains hydrogen cyanide and amygdalin, especially in its endocarp.
      Therefore, prebrewed AS that is devoid of endocarp has been traditionally used.
      In the present study, amygdalin content of the prebrewed AS was significantly
      lower (2.73 +/- 0.32 MUg/ml; p < 0.01) than the content in the extract that
      contained the endocarps (28.50 +/- 6.71 MUg/ml); amygdalin content corresponded
      to 10% of the extract in the present study. Because of single oral dose toxicity
      of prebrewed AS according to the recommendation of Korea Food and Drug
      Administration Guidelines (2009-116, 2009), which was based on single oral dose
      toxicity study of prebrewed AS, mortality due to toxic principles was
      significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of
      1 female rat and 1 male rat at the end of 2 hr of administration. Based on these
      results, the 50% lethal dose in both male and female rats was determined to be
      9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart
      rate were observed as prebrewed AS treatment-related toxicological signs; these
      signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated
      rats. In addition, no changes were observed in body weight, organ weight, gross
      features, and histopathological parameters with 2,000 mg/kg of AS in both male
      and female rats. These findings serve as direct evidence that amygdalin in AS is
      the toxic principle, which can be reduced by the traditional prebrewing method
      involving the exclusion of endocarp. 

PMID- 24278635
TI  - In Vitro Evaluation of Antimicrobial Activity of Lactic Acid Bacteria against
      Clostridium difficile.
AB  - Clostridium difficile infection (CDI) has become a significant threat to public
      health. Although broad-spectrum antibiotic therapy is the primary treatment
      option for CDI, its use has evident limitations. Probiotics have been proved to
      be effective in the treatment of CDI and are a promising therapeutic option for
      CDI. In this study, 4 strains of lactic acid bacteria (LAB), namely,
      Lactobacillus rhamnosus (LR5), Lactococcuslactis (SL3), Bifidobacterium breve
      (BR3), and Bifidobacterium lactis (BL3) were evaluated for their anti-C.
      difficile activity. Co-culture incubation of C. difficile (10(6) and 10(10)
      CFU/ml) with each strain of LAB indicated that SL3 possessed the highest
      antimicrobial activity over a 24-hr period. The cell-free supernatants of the 4
      LAB strains exhibited MIC50 values between 0.424 mg/ml (SL3) and 1.318 (BR3)
      mg/ml. These results may provide a basis for alternative therapies for the
      treatment of C. difficile-associated gut disorders. 

PMID- 24278636
TI  - Comparison between Source-induced Dissociation and Collision-induced Dissociation
      of Ampicillin, Chloramphenicol, Ciprofloxacin, and Oxytetracycline via Mass
      Spectrometry.
AB  - Mass spectrometry (MS) is a very powerful instrument that can be used to analyze
      a wide range of materials such as proteins, peptides, DNA, drugs, and polymers.
      The process typically involves either chemical or electron (impact) ionization of
      the analyte. The resulting charged species or fragment is subsequently identified
      by the detector. Usually, single mass uses source-induced dissociation (SID),
      whereas mass/mass uses collision-induced dissociation (CID) to analyze the
      chemical fragmentations Each technique has its own advantages and disadvantages.
      While CID is most effective for the analysis of pure substances, multiple- step
      MS is a powerful technique to get structural data. Analysis of veterinary drugs
      ampicillin, chloramphenicol, ciprofloxacin, and oxytetracycline serves to
      highlight the slight differences between SID and CID. For example, minor
      differences were observed between ciprofloxacin and oxytetracycline via SID or
      CID. However, distinct fragmentation patterns were observed for ampicllin
      depending on the analysis method. Both SID and CID showed similar fragmentation
      spectra but different signal intensities for chloramphenicol. There are several
      factors that can influence the fragmentation spectra, such as the collision
      energy, major precursor ion, electrospray mode (positive or negative), and sample
      homogeneity. Therefore, one must select a fragmentation method on an empirical
      and case-by-case basis. 

PMID- 24278637
TI  - Effects of beryllium on human serum immunoglobulin and lymphocyte subpopulation.
AB  - To investigate the effects of short-term exposure of beryllium on the human
      immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95,
      and NK cells, andthe proportion of B cells and TNFalpha level in peripheral blood
      and immunoglobulins in the serum of 43 exposed workers and 34 healthy control
      subjects were studied. External exposure to beryllium was measured by atomic
      absorption spectrometer as recommended by the NIOSH analytical method 7300. T
      lymphocyte subpopulation analysis was carried out with flow cytometer. The
      working duration of exposed workers was less than 3 months and the mean ambient
      beryllium level was 3.4 MUg/m(3), 112.3 MUg/m(3), and 2.3 MUg/m(3) in molding
      (furnace), deforming (grinding), and sorting processes, respectively (cited from
      Kim et al., 2008). However, ambient beryllium level after process change was non
      detectable (< 0.1 MUg/m(3)). The number of T lymphocytes and the amount of
      immunoglobulins in the beryllium-exposed workers and control subjects were not
      significantly different, except for the total number of lymphocytes and CD95
      (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed
      individuals than in the healthy control subjects. Multiple logistic regression
      analysis showed lymphocytes to be affected by beryllium exposure (odd ratio =
      7.293; p < 0.001). These results show that short-term exposure to beryllium does
      not induce immune dysfunction but is probably associated with lymphocytes
      proliferation. 

PMID- 24278638
TI  - Comparison of toxicity and deposition of nano-sized carbon black aerosol prepared
      with or without dispersing sonication.
AB  - Nanotoxicological research has shown toxicity of nanomaterials to be inversely
      related to particle size. However, the contribution of agglomeration to the
      toxicity of nanomaterials has not been sufficiently studied, although it is known
      that agglomeration is associated with increased nanomaterial size. In this study,
      we prepared aerosols of nano-sized carbon black by 2 different ways to verify the
      effects of agglomeration on the toxicity and deposition of nano-sized carbon
      black. The 2 methods of preparation included the carbon black dispersion method
      that facilitated clustering without sonication and the carbon black dispersion
      method involving sonication to achieve scattering and deagglomeration. Male
      Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days
      or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols
      averaged 2.08 MUm (for aerosol prepared without sonication; group N) and 1.79 MUm
      (for aerosol prepared without sonication; group S). The average concentration of
      carbon black during the exposure period for group N and group S was 13.08 +/-
      3.18 mg/m(3) and 13.67 +/- 3.54 mg/ m(3), respectively, in the 3-day experiment.
      The average concentration during the 2-week experiment was 9.83 +/- 3.42 mg/m(3)
      and 9.08 +/- 4.49 mg/m(3) for group N and group S, respectively. The amount of
      carbon black deposition in the lungs was significantly higher in group S than in
      group N in both 3-day and 2-week experiments. The number of total cells,
      macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL)
      fluid, and the number of total white blood cells and neutrophils in the blood in
      the 2- week experiment were significantly higher in group S than in normal
      control. However, differences were not found in the inflammatory cytokine levels
      (IL-1beta, TNF-alpha, IL-6, etc.) and protein indicators of cell damage (albumin
      and lactate dehydrogenase) in the BAL fluid of both group N and group S as
      compared to the normal control. In conclusion, carbon black aerosol generated by
      sonication possesses smaller nanoparticles that are deposited to a greater extent
      in the lungs than is aerosol formulated without sonication. Additionally, rats
      were narrowly more affected when exposed to carbon black aerosol generated by
      sonication as compared to that produced without sonication. 

PMID- 24278639
TI  - A study on the prevention of salmonella infection by using the aggregation
      characteristics of lactic Acid bacteria.
AB  - Salmonella is one of the major pathogenic bacteria that cause food poisoning.
      This study investigated whether heat-killed as well as live Lactobacillus
      protects host animal against Salmonella infection. Live and heat-killed
      Lactobacillusacidophilus was administered orally to Sprague-Dawley rats for 2
      weeks before the rats were inoculated with Salmonella. Rise in body temperature
      was moderate in the group that was treated with heat-killed bacteria as compared
      to the Salmonella control group. The mean amount of feed intake and water
      consumption of each rat in the heat-killed bacteria group were nearly normal. The
      number of fecal Salmonellae was comparable between the live and the heat-killed
      L. acidophilus groups. This finding shows that L. acidophilus facilitates the
      excretion of Salmonella. Moreover, the levels of pro inflammatory cytokines,
      including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, in the
      heat-killed L. acidophilus group were significantly lower when compared to the
      levels in the Salmonella control group. These results indicate that nonviable
      lactic acid bacteria also could play an important role in preventing infections
      by enteric pathogens such as Salmonella. 

PMID- 24278640
TI  - Urinary Arsenic Concentrations and their Associated Factors in Korean Adults.
AB  - Arsenic (As) is a well-known human carcinogen and its dietary exposure has been
      found to be the major route of entry into general population. This study was
      performed to assess the body levels of As and their associated factors in Korean
      adults by analyzing total As in urine. Urine and blood samples were collected
      from 580 adults aged 20 years and older, who had not been exposed to As
      occupationally. Demographic information was collected with the help of a standard
      questionnaire, including age, smoking, alcohol intake, job profiles, and diet
      consumed in the last 24 hrs of the study. Total As, sum of As(III), As(V),
      monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), in urine was determined
      using atomic absorption spectrometer involving hydride generation method. The
      geometric mean concentration of total As in urine was 7.10 MUg/L. Urine As was
      significantly higher in men (7.63 MUg/L) than in women (6.75 MUg/ L). Age,
      smoking, alcohol consumption, and job profiles of study subjects did not
      significantly affect the concentration of As in urine. No significant
      relationship was observed between body mass index (BMI), Fe, and total
      cholesterol in serum and urinary As. Urine As level was positively correlated
      with seaweeds, fishes & shellfishes, and grain intake. A negative correlation
      between urinary As level and HDL-cholesterol in serum and meat intake was
      observed. Overall, these results suggest that urinary As concentration could be
      affected by seafood consumption. Therefore, people who frequently consume seafood
      and grain need to be monitored for chronic dietary As exposure. 

PMID- 24278641
TI  - Determination of cyanogenic compounds in edible plants by ion chromatography.
AB  - Cyanogenic glycosides are HCN-producing phytotoxins; HCN is a powerful and a
      rapidly acting poison. It is not difficult to find plants containing these
      compounds in the food supply and/or in medicinal herb collections. The objective
      of this study was to investigate the distribution of total cyanide in nine genera
      (Dolichos, Ginkgo, Hordeum, Linum, Phaseolus, Prunus, Phyllostachys, Phytolacca,
      and Portulaca) of edible plants and the effect of the processing on cyanide
      concentration. Total cyanide content was measured by ion chromatography following
      acid hydrolysis and distillation. Kernels of Prunus genus are used medicinally,
      but they possess the highest level of total cyanide of up to 2259.81 CN(-)/g dry
      weight. Trace amounts of cyanogenic compounds were detected in foodstuffs such as
      mungbeans and bamboo shoots. Currently, except for the WHO guideline for cassava,
      there is no global standard for the allowed amount of cyanogenic compounds in
      foodstuffs. However, our data emphasize the need for the guidelines if plants
      containing cyanogenic glycosidesare to be developed as dietary supplements. 

PMID- 24278642
TI  - Post-carotid endarterectomy cerebral hyperperfusion syndrome : is it preventable
      by strict blood pressure control?
AB  - OBJECTIVE: Cerebral hyperperfusion syndrome (CHS) is a serious complication after
      carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as
      techniques have improved. This study evaluates the role of strict blood pressure
      (BP) control for the prevention of CHS. METHODS: All 18 patients who received CEA
      from February 2009 through November 2012 were retrospectively reviewed. All
      patients were routinely managed in an intensive care unit by a same protocol. The
      cerebral perfusion state was evaluated on the basis of the regional cerebral
      blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity
      by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7
      days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or
      in the mean velocity by TCD compared with preoperative values) or CHS was
      detected, BP was maintained below 120/80 mm Hg. RESULTS: TCD and pCT data on the
      patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in
      the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in
      the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical
      CHS for one month after CEA. Furthermore, no patients developed additional
      neurological deficits related to postoperative cerebrovascular complications.
      CONCLUSION: Intensive care with strict BP control (<140/90 mm Hg) achieved a low
      prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that
      intensive care with strict BP control can prevent the prevalence of post-CEA CHS.

PMID- 24278643
TI  - Clinical Comparison of 30-Day Mortalities and 6-Month Functional Recoveries after
      Spontaneous Intracerebral Hemorrhage in Patients with or without End-Stage Renal
      Disease.
AB  - OBJECTIVE: The aim of this study was to determine 30-day mortality and 6-month
      functional recovery rates in spontaneous intracerebral hemorrhage (S-ICH)
      patients undergoing hemodialysis treatment for end-stage renal disease (ESRD),
      and to compare the outcomes of these patients and S-ICH patients without ESRD.
      METHODS: The medical records of 1943 S-ICH patients from January 2000 to December
      2011 were retrospectively analyzed with focus on demographic, radiological, and
      laboratory characteristics. RESULTS: A total of 1558 supratentorial S-ICH
      patients were included in the present study and 102 (6.5%) were ESRD patients.
      The 30-day mortality of the S-ICH patients with ESRD was 53.9%, and 29.4%
      achieved good functional recovery at 6 months post-S-ICH. Multivariate analysis
      showed that age, Glasgow Coma Scale (GCS) score, pupillary abnormality,
      ventricular extension of hemorrhage, hemorrhagic volume, hematoma enlargement,
      anemia, and treatment modality were independently associated with 30-day
      mortality in S-ICH patients with ESRD (p<0.05), and that GCS score, volume of
      hemorrhage, conservative treatment, and shorter hemodialysis duration was
      independently associated with good functional recovery at 6 months post-S-ICH in
      patients with ESRD (p<0.05). CONCLUSION: This retrospective study showed worse
      outcome after S-ICH in patients with ESRD than those without ESRD; 30-day
      mortality was four times higher and the functional recovery rate was
      significantly lower in S-ICH patients with ESRD than in S-ICH patients without
      ESRD.

PMID- 24278644
TI  - Intracavitary radiation therapy for recurrent cystic brain tumors with holmium
      166-chico : a pilot study.
AB  - OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control
      of cystic tumors has been tried with a benefit of localized internal radiation.
      The authors treated cystic brain tumor patients with Holmium-166-chitosan complex
      (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and
      biodegradable chit polymer, and evaluated the safety and effective measurement
      for response. METHODS: Twenty-two patients with recurrent cystic brain tumor
      and/or located in a deep or eloquent area were enrolled in this pilot study. The
      cyst volume and wall thickness were determined on CT or MRI to assess
      radiological response. The activity of Ho-166-chico injected via Ommaya reservoir
      was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There
      was neither complications related to systemic absorption nor leakage of Ho-166
      chico in all 22 patients. But, two cases of oculomotor paresis were observed in
      patients with recurrent craniopharyngioma. Radiological response was seen in 14
      of 20 available follow-up images (70%). Seven patients of 'evident' radiological
      response experienced more than 25% decrease of both cyst volume and wall
      thickness. Another 7 patients with 'suggestive' response showed decrease of cyst
      volume without definitive change of the wall thickness or vice versa. All
      patients with benign tumors or low grade gliomas experienced symptomatic
      improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic
      tumor is a safe method of palliation without serious complications. The
      determination of both minimal effective dosage and time interval of repeated
      injection through phase 1 trial could improve the results in the future.

PMID- 24278645
TI  - Surgical versus Conservative Treatment for Lumbar Disc Herniation with Motor
      Weakness.
AB  - OBJECTIVE: The aim of this study is to assess outcomes during first one year for
      patients with severe motor weakness caused by lumbar disc herniation that
      underwent surgical or nonsurgical treatment. METHODS: The 46 patients with motor
      weakness because of lumbar disc herniation who were treated at neurosurgical
      department and rehabilitation in our hospital from 2006 to 2010, retrospectively.
      Each group had 26 surgical treatments and 20 conservative treatments. We followed
      up 1, 3, 6 months and 12 month and monitored a Visual Analogue rating Scale (VAS)
      of back and leg pain, Oswestry Disability Index (ODI) and degree of motor
      weakness. We analyzed the differences between surgical and nonsurgical groups
      using Mann-Whitney U test and repeat measure ANOVA in each follow-up periods.
      RESULTS: In the recovery of motor weakness, surgical treatment uncovered a rapid
      functional recovery in the early periods (p=0.003) and no difference between
      groups at the end of follow-up period was found (p>0.05). In VAS of back and leg,
      the interaction between time and group was not found (p>0.05) and there was no
      difference between groups (p>0.05). In ODI, the interaction between time and
      group was not found (p>0.05) and there was no difference between groups (p>0.05).
      CONCLUSION: Surgical treatment for motor weakness caused by herniated
      intervertebral disc resulted in a rapid recovery in the short-term period,
      especially 1 month. We think early and proper surgical treatment in a case of
      motor weakness from disc herniation could be a good way for providing a chance
      for rapid alleviation.

PMID- 24278646
TI  - Anterior cervical discectomy and fusion using a stand-alone polyetheretherketone
      cage packed with local autobone : assessment of bone fusion and subsidence.
AB  - OBJECTIVE: It remains debatable whether cervical spine fusion cages should be
      filled with any kind of bone or bone substitute. Cortical and subcortical bone
      from the anterior and posterior osteophytes of the segment could be used to fill
      the cage. The purposes of the present study are to evaluate the clinical outcomes
      and radiological outcomes including bone fusion and subsidence that occurred
      after anterior cervical discectomy and fusion using a stand-alone cage packed
      with local autobone graft. METHODS: Thirty-one patients who underwent anterior
      cervical fusion using a stand-alone polyetheretherketone (PEEK) cage packed with
      local autobone graft from July 2009 to december 2011 were enrolled in this study.
      Bone fusion was assessed by cervical plain radiographs and computed tomographic
      scan. Nonunion was evaluated according to the absence of bony bridge on computed
      tomographic scan. Subsidence was defined as a >=2 mm decrease of the interbody
      height at the final follow-up compared to that measured at the immediate
      postoperative period. RESULTS: Subsidence was observed in 7 patients (22.6%). Of
      7 patients with subsidence greater 2 mm, nonunion was developed in 3. Three
      patients with subsidence greater 2 mm were related with endplate damage during
      intraoperative endplate preparation. Solid bone fusion was achieved in 28 out of
      31 patients (90.3%). CONCLUSION: With proper patient selection and careful
      endplate preparation, anterior cervical discectomy and fusion (ACDF) using a
      stand-alone PEEK cage packed with local autobone graft could be a good
      alternative to the standard ACDF techniques with plating.

PMID- 24278648
TI  - Sagittal sacropelvic morphology and balance in patients with sacroiliac joint
      pain following lumbar fusion surgery.
AB  - OBJECTIVE: To investigate the sagittal sacropelvic morphology and balance of the
      patients with SIJ pain following lumbar fusion. METHODS: Among 452 patients who
      underwent posterior lumbar interbody fusion between June 2009 and January 2013,
      patients with postoperative SIJ pain, being responded to SIJ block were enrolled.
      For a control group, patients matched for sex, age group, the number of fused
      level and fusion to sacrum were randomly selected. Patients were assessed
      radiologic parameters including lumbar lordosis, pelvic incidence (PI), pelvic
      tilt (PT) and sacral slope (SS). To evaluate the sagittal sacropelvic morphology
      and balance, the ratio of PT/PI, SS/PI and PT/SS were analyzed. RESULTS: A total
      of 28 patients with SIJ pain and 56 patients without SIJ pain were assessed.
      Postoperatively, SIJ pain group showed significantly greater PT (p=0.02) than non
      SIJ pain group. Postoperatively, PT/PI and SS/PI in SIJ pain group was
      significantly greater and smaller than those in non-SIJ pain group respectively
      (p=0.03, 0.02, respectively) except for PT/SS (p=0.05). SIJ pain group did not
      show significant postoperative changes of PT/PI and SS/PI (p=0.09 and 0.08,
      respectively) while non-SIJ pain group showed significantly decrease of PT/PI
      (p=0.00) and increase of SS/PI (p=0.00). CONCLUSION: This study presents
      different sagittal sacropelvic morphology and balance between the patients
      with/without SIJ pain following lumbar fusion surgery. The patients with SIJ pain
      showed retroversed pelvis and vertical sacrum while the patients without SIJ pain
      have similar morphologic features with asymptomatic populations in the
      literature.

PMID- 24278647
TI  - Minimum 3-year outcomes in patients with lumbar spinal stenosis after bilateral
      microdecompression by unilateral or bilateral laminotomy.
AB  - OBJECTIVE: Lumbar spine stenosis (LSS) can result in symptomatic compression of
      the neural elements, requiring surgical treatment if conservative management
      fails. Minimally invasive surgery has come to be more commonly used for the
      treatment of LSS. The current study describes outcomes of bilateral
      microdecompression by unilateral or bilateral laminotomy (BML) for degenerative
      LSS after a minimum follow-up period of 3 years and investigates factors that
      result in a poor outcome. METHODS: Twenty-one patients who were followed-up for
      at least 3 years were included in this study. For clinical evaluation, the
      Japanese Orthopedic Association (JOA) scoring system for low back pain was used.
      The modified grading system of Finneson and Cooper was used for outcome
      assessment. Radiographic evaluation was also performed for spondylolisthesis,
      sagittal rotation angle, and disc height. RESULTS: Twenty-one patients (10 men,
      11 women) aged 53-82 years (64.1+/-8.9 years) were followed-up for a minimum of 3
      years (36-69 months). During follow-up, two patients underwent reoperation.
      Average preoperative JOA score and clinical symptoms, except persistent low back
      pain, improved significantly at the latest follow-up. There were no significant
      differences in radiological findings preoperatively and postoperatively. Thirteen
      patients (61.9%) had excellent to fair outcomes. CONCLUSION: BML resulted in a
      favorable and persistent outcome for patients with degenerative LSS without
      radiological instability over a mid-term follow-up period. Persistent low back
      pain unrelated to postoperative instability adversely affects mid-term outcomes.

PMID- 24278649
TI  - The Comparison of Sagittal Spinopelvic Parameters between Young Adult Patients
      with L5 Spondylolysis and Age-Matched Control Group.
AB  - OBJECTIVE: To compare spinopelvic parameters in young adult patients with
      spondylolysis to those in age-matched patients without spondylolysis and
      investigate the clinical impact of sagittal spinopelvic parameters in patients
      with L5 spondylolysis. METHODS: From 2009 to 2012, a total of 198 young adult
      male patients with spondylolysis were identified. Eighty age-matched patients
      without spondylolysis were also selected. Standing lateral films that included
      both hip joints were obtained for each subject. Pelvic incidence (PI), sacral
      slope (SS), pelvic tilt, lumbar lordosis angle, sacral inclination, lumbosacral
      angle, and sacral table angle were measured in both groups. A comparative study
      of the spinopelvic parameters of these two groups was performed using SPSS 15.0
      (SPSS Inc., Chicago, IL, USA). RESULTS: Among the aforementioned spinopelvic
      parameters, PI, SS and STA were significantly different between patients with
      spondylolysis and those without spondylolysis. PI and SS were higher in the
      spondylolysis group than in the control group, but STA was lower in the
      spondylolysis group than in the control group. CONCLUSION: PI and SS were higher
      in the spondylolysis group than in the control group, but STA was lower in the
      spondylolysis group than in the control group. Patients with spondylolysis have
      low STA at birth, which remains constant during growth; a low STA translates into
      high SS. As a result, PI is also increased in accordance with SS. Therefore, we
      suggest that STA is an important etiologic factor in young adult patients with L5
      spondylolysis.

PMID- 24278650
TI  - Natural course of initially non-operated cases of acute subdural hematoma : the
      risk factors of hematoma progression.
AB  - OBJECTIVE: The objectives of the present study were to characterize the natural
      course of initially non-operated traumatic acute subdural hematoma (ASDH) and to
      identify the risk factors of hematoma progression. METHODS: Retrospective
      analysis was performed using sequential computed tomography (CT) images
      maintained in a prospective observational database containing 177 ASDH cases
      treated from 2005 to 2011. Patients were allocated to four groups as followings;
      136 (76.8%) patients to the spontaneous resolution group, 12 (6.8%) who underwent
      operation between 4 hours and 7 days to the rapid worsening group (RWG), 24
      (13.6%) who experienced an increase of hematoma and that underwent operation
      between 7 and 28 days to the subacute worsening group (SWG), and 5 (2.8%) who
      developed delayed aggravation requiring surgery from one month after onset to the
      delayed worsening group (DWG). Groups were compared with respect to various
      factors. RESULTS: No significant intergroup difference was found with respect to
      age, mechanism of injury, or initial Glasgow Coma Scale. The presence of combined
      cerebral contusion or subarachnoid hemorrhage was found to be a significant
      prognostic factor. Regarding CT findings, mixed density was common in the RWG and
      the SWG. Midline shifting, hematoma thickness, and numbers of CT slices
      containing hematoma were significant prognostic factors of the RWG and the SWG.
      Brain atrophy was more severe in the SWG and the DWG. CONCLUSION: A large
      proportion of initially non-operated ASDHs worsen in the acute or subacute phase.
      Patients with risk factors should be monitored carefully for progression by
      repeat CT imaging.

PMID- 24278651
TI  - The Effectiveness of Early Tracheostomy (within at least 10 Days) in Cervical
      Spinal Cord Injury Patients.
AB  - OBJECTIVE: This study aimed to determine the optimal time for tracheostomy by
      evaluating the benefits and safety of early versus late tracheostomy in spinal
      cord injury (SCI) patients. METHODS: We retrospectively reviewed a total of 254
      patients with spinal cord injury. Of them, we selected 21 spinal cord injury
      patients who required tracheostomy due to long-term mechanical ventilation and
      analyzed their medical records. The patients were categorized into two groups.
      Early tracheostomy was performed day 1-10 from intubation in 10 patients and the
      late tracheostomy was performed after day 10 in 11 cases. We also evaluated the
      duration of mechanical ventilation, stay in the ICU and complications related to
      tracheostomy, the injury level of and clinical severity. All data was analyzed
      using SPSS 18.0/WIN. RESULTS: The early tracheostomy offered clear advantages for
      shortening the total ICU stay (20.8 day vs. 38.0 day, p=0.010). There was also
      statistically significant reduction in the total length of time on mechanical
      ventilation (5.2 day vs. 29.2 day, p=0.009). However, the reductions in the
      incidence of pneumonia (40% vs. 82%) and the length of ICU stay post to
      tracheostomy (6 day vs. 15 day) were found to be statistically not significant.
      There were also no statistically significant differences in the injury level and
      clinical severity between the groups. CONCLUSION: We concluded that the early
      tracheostomy (at least 10 days) is beneficial for SCI patients who are likely to
      require prolonged mechanical ventilation.

PMID- 24278652
TI  - Analysis of risk factors and management of cerebrospinal fluid morbidity in the
      treatment of spinal dysraphism.
AB  - OBJECTIVE: Spinal dysraphism defects span wide spectrum. Wound dehiscence is a
      common postoperative complication, and is a challenge in the current management
      of cerebrospinal fluid (CSF) leaks and wound healing. The purpose of this study
      is to evaluate the risks of CSF-related morbidity in the surgical treatment of
      spinal dysraphism. METHODS: Ten patients with spinal dysraphism were included in
      this retrospective study. The median age of the cohort was 4.8 months. To assess
      the risk of CSF morbidity, we measured the skin lesion area and the percentage of
      the skin lesion area relative to the back surface for each patient. We then
      analyzed the relationship between morbidity and the measured skin lesion area or
      related factors. RESULTS: The overall median skin lesion area was 36.2 cm(2)
      (n=10). The percentage of the skin lesion area relative to the back surface
      ranged from 0.6% to 18.1%. During surgical reconstruction, 4 patients required
      subsequent operations to repair CSF morbidity. The comparison of the mean area of
      skin lesions between the CSF morbidity group and the non-CSF morbidity group was
      statistically significant (average volume skin lesion of 64.4+/-32.5 cm(2) versus
      27.7+/-27.8 cm(2), p<0.05). CSF morbidity tended to occur either when the skin
      lesion area was up to 44.2 cm(2) or there was preexisting fibrosis before
      revision with an accompanying broad-based dural defect. CONCLUSION: Measuring the
      lesion area, including the skin, dura, and related surgical parameters, offers
      useful information for predicting wound challenges and selecting appropriate
      reconstructive surgery methods.

PMID- 24278653
TI  - Quantitative evaluation of median nerve motor function in carpal tunnel syndrome
      using load cell : correlation with clinical, electrodiagnostic, and
      ultrasonographic findings.
AB  - OBJECTIVE: Major complaints of carpal tunnel syndrome (CTS) are sensory
      components. However, motor deficit also impedes functional status of hand.
      Contrary to evaluation of sensory function, the objective, quantitative
      evaluation of median nerve motor function is not easy. The motor function of
      median was evaluated quantitatively using load cell and its correlation with
      findings of electrodiagnostic study (EDS) was evaluated. METHODS: Objective motor
      function of median nerve was evaluated by load cell and personal computer-based
      measurement system. All of the measurement was done in patients diagnosed as
      having idiopathic CTS by clinical features and EDS findings. The strength of
      thumb abduction and index finger flexion was measured in each hand three times,
      and the average value was used to calculate thumb index ratio (TIR). The
      correlation of TIR with clinical, EDS, and ultrasonographic findings were
      evaluated. RESULTS: The TIR was evaluated in 67 patients (119 hands). There were
      14 males and 53 females, mean age were 57.6 years (range 28 to 81). The higher
      preoperative nerve conductive studies grade of the patients, the lower TIR was
      observed [p<0.001, analysis of variance (ANOVA)]. TIR of cases with thenar
      atrophy were significantly lower than those without (p<0.001, t-test). TIR were
      significantly lower in patients with severe median nerve swelling in
      ultrasonography (p=0.042, ANOVA). CONCLUSION: Measurements of median nerve motor
      function using load cell is a valuable evaluation tool in CTS. It might be
      helpful in detecting subclinical motor dysfunction before muscle atrophy
      develops.

PMID- 24278654
TI  - Rupture of de novo anterior communicating artery aneurysm 8 days after the
      clipping of ruptured middle cerebral artery aneurysm.
AB  - Rapidly developed de novo aneurysm is very rare. We present a rapidly developed
      and ruptured de novo anterior communicating aneurysm 8 days after the rupture of
      another aneurysm. This de novo aneurysm was not apparent in the initial 3
      dimensional computed tomography and digital subtraction angiography. We reviewed
      the literature and discussed possible mechanisms for the development of this de
      novo aneurysm. 

PMID- 24278655
TI  - Bilateral superior cerebellar artery infarction after stent-angioplasty for
      internal carotid artery stenosis.
AB  - Spontaneous bilateral cerebellar infarction in the territory of the superior
      cerebellar arteries is extremely rare. Occasionally there have been reports of
      bilateral cerebellar infarction due to vertebrobasilar atherosclerotic occlusion
      or stenosis, whereas no report of bilateral cerebellar infarction due to
      complicated hemodynamic changes. In this report, we present a patient with
      bilateral cerebral infarctions related to stenoses of bilateral internal carotid
      arteries, in whom vertebrobasilar system was supplied by multiple collaterals
      from both posterior communicating arteries and right external carotid artery. We
      performed stent-angioplasty of bilateral internal cerebral arterial stenosis, and
      then acute infarction developed on bilateral superior cerebellar artery
      territories. The authors assumed that the infarction occurred due to hemodynamic
      change between internal carotid artery and external carotid artery after stent
      angioplasty for stenosis of right internal carotid artery. 

PMID- 24278656
TI  - Rotational Vertebral Artery Compression : Bow Hunter's Syndrome.
AB  - Bow hunter's syndrome (BHS) is rare cause of vertebrobasilar insufficiency that
      arises from mechanical compression of the vertebral artery by head rotation.
      There is no standardized diagnostic regimen or treatment of BHS. Recently, we
      experienced 2 cases resisted continues medication and treated by surgical
      approach. In both cases, there were no complications after surgery and there were
      improvements in clinical symptoms. Thus, we describe our cases with surgical
      decompression with a review of the relevant medical literature. 

PMID- 24278657
TI  - Malignant solitary fibrous tumor of tandem lesions in the skull and spine.
AB  - A Solitary Fibrous Tumor (Sft) Is A Rare Neoplasm Originated From The Pleura, But
      They Can Occur In A Variety Of Extrathoracic Regions. Although Many Cases Of
      Primary Sft Have Been Reported, There Are Extremely Rare Repots To Date Of A
      Malignant Sft In The Spine Or Skull. A 54-year-woman Visited Our Hospital Due To
      Low Back Pain And Both Leg Radiating Pain. Several Imaging Studies Including
      Magnetic Resonance Imaging And Computed Tomography Revealed Expansive Enhanced
      Lesions In The Occipital Bone, T8, S1-2, And Ilium, With Neural Tissue
      Compression. We Performed Surgical Resection Of The Tumor In Each Site, And
      Postoperative Radiosurgery And Chemotherapy Were Performed. However, After Six
      Months, Tumors Were Recurred And Metastasized In Multiple Regions Including Whole
      Spine And Lung. The Authors Report Here The First Case Of Patient With Malignant
      Sft Of Tandem Lesions In The Various Bony Structures, Including Skull, Thoracic
      Spine, And Sacral Spine, With A Rapid Recurrence And Metastasis. Although
      Malignant Sft Is Extremely Rare, It Should Be Considered In The Differential
      Diagnosis And Carful Follow-up Is Needed. 

PMID- 24278658
TI  - Incidental Superior Hypophygeal Artery Aneurysm Embedded within Pituitary
      Adenoma.
AB  - Intra-cranial aneurysm can be incidental findings in patients with pituitary
      adenomas, and are usually located outside the pituitary region. However, the
      coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas
      is extremely rare. We report a patient with an incidental superior hypophygeal
      aneurysm embedded within a non-functional pituitary adenoma which was treated by
      transsphenoidal surgery after endovascular coil embolization. 

PMID- 24278659
TI  - Spinal Hemangiopericytoma Which Needed Intraoperative Embolization due to
      Unexpected Bleeding.
AB  - Spinal intradural hemangiopericytoma is a very rare tumor and can be
      characterized by massive bleeding during surgeries, frequent recurrence, and
      metastasis. However, definite radiologic differential points of
      hemangiopericytoma are not known. We describe an unexpected hemangiopericytoma
      case with large bleeding and management of the tumor. A 21-year-old man visited
      complaining of progressive neck pain and tingling sensation in both hands.
      Magnetic resonance imaging of his spine revealed C1-2 ventral intradural mass.
      When the dura was opened, the intradural tumor was placed behind spinal accessary
      nerves. The tumor was partially exposed only after some accessary nerves had been
      cut. When internal debulking was performing, unexpected bleeding was noted and it
      was difficult to control because of narrow surgical field and hypervascularity.
      Intraoperative spinal angiography and embolization were performed. The tumor was
      completely removed after embolization. Pathological diagnosis was consistent with
      hemangiopericytoma. When surgeons meet a flesh-red tumor that bleeds unexpectedly
      during surgery, hemangiopericytoma may be considered. When feeder control is hard
      due to reciprocal location of spinal cord, the tumor, and feeders, intraoperative
      angiography and embolization may be a possible option. 

PMID- 24278660
TI  - Totally ossified metaplastic spinal meningioma.
AB  - A 61-year-old woman with a very rare case of totally ossified large thoracic
      spinal metaplastic meningioma, showing progressing myelopathy is presented.
      Computed tomographic images showed a large totally ossfied intradural round mass
      occupying the spinal canal on T9-10 level. Magnetic resonance imaging revealed a
      large T9-10 intradural extramedullary mass that was hypointense to spinal cord on
      T1- and T2-weighted sequences, partial enhancement was apparent after Gadolinium
      administration. The spinal cord was severely compressed and displaced toward the
      right at the level of T9-10. Surgical removal of the tumor was successfully
      accomplished via the posterior midline approach and the histological diagnosis
      verified an ossified metaplastic meningioma. The clinical neurological symptoms
      of patient were improved postoperatively. In this article we discuss the surgical
      and pathological aspects of rare case of spinal totally ossified metaplastic
      meningioma. 

PMID- 24278661
TI  - A long-term survival case of a primary malignant intracerebral nerve sheath
      tumor.
AB  - We report a long-term survival case of a primary malignant intracerebral nerve
      sheath tumor (MINST) occurring in the right frontal lobe of a 13-year old boy.
      After the gross total resection (GTR), we have performed radiation therapy but it
      recurred 50 months after the surgery, so the second GTR was performed. Later,
      second tumor recurrence was found 4 months after the second surgery. Subsequently
      the third GTR, radiotherapy, and chemotherapy were carried out. At present, the
      patient has been remaining alive for 77 months without evidence of tumor
      recurrence. According to the previous reports, the primary MINST is very rare :
      there are only 8 cases reported. It is also a fast-growing, invasive tumor with
      poor outcome. This is the first case that had no recurrence for 50 months after
      the surgery among the reported cases that had been followed up for more than 5
      years. It is supposed that a period of recurrence free survival after GTR and low
      mitotic activity are associated with the patient's prognosis. A GTR followed by
      adjuvant radiation therapy and chemotherapy will be recommended to patients of
      MINST. 

PMID- 24278662
TI  - Chronic subdural hematoma after eccentric exercise using a vibrating belt
      machine.
AB  - We report a case of bilateral chronic subdural hematoma (CSDH) in a 75-year-old
      man after exercise using a vibrating belt machine on the head. He suffered from
      headache and intermittent left side numbness for ten days. He denied any head
      injuries except eccentric exercise using a vibrating belt on his own head for 20
      days. An MRI revealed bilateral CSDH. The hematoma was isodense on the CT scan.
      We made burr-holes on the both sides under local anesthesia. We identified the
      neomembrane and dark red subdural fluid on both sides. In the postoperative CT
      scan, we found an arachnoid cyst on the left temporal pole. Although the
      arachnoid cyst itself is asymptomatic, trivial injury such as vibrating the head
      may cause a CSDH. 

PMID- 24278663
TI  - Intractable occipital neuralgia caused by an entrapment in the semispinalis
      capitis.
AB  - Occipital neuralgia is a rare pain syndrome characterized by periodic lancinating
      pain involving the occipital nerve complex. We present a unique case of
      entrapment of the greater occipital nerve (GON) within the semispinalis capitis,
      which was thought to be the cause of occipital neuralgia. A 66-year-old woman
      with refractory left occipital neuralgia revealed an abnormally low-loop of the
      left posterior inferior cerebellar artery on the magnetic resonance imaging,
      suggesting possible vascular compression of the upper cervical roots. During
      exploration, however, the GON was found to be entrapped at the perforation site
      of the semispinalis capitis. There was no other compression of the GON or of C1
      and C2 dorsal roots in their intracranial course. Postoperatively, the patient
      experienced almost complete relief of typical neuralgic pain. Although occipital
      neuralgia has been reported to occur by stretching of the GON by inferior oblique
      muscle or C1-C2 arthrosis, peripheral compression in the transmuscular course of
      the GON in the semispinalis capitis as a cause of refractory occipital neuralgia
      has not been reported and this should be considered when assessing surgical
      options for refractory occipital neuralgia. 

PMID- 24278665
TI  - Mechanisms for covalent immobilization of horseradish peroxidase on ion-beam
      treated polyethylene.
AB  - The surface of polyethylene was modified by plasma immersion ion implantation.
      Structure changes including carbonization and oxidation were observed. High
      surface energy of the modified polyethylene was attributed to the presence of
      free radicals on the surface. The surface energy decay with storage time after
      treatment was explained by a decay of the free radical concentration while the
      concentration of oxygen-containing groups increased with storage time.
      Horseradish peroxidase was covalently attached onto the modified surface by the
      reaction with free radicals. Appropriate blocking agents can block this reaction.
      All aminoacid residues can take part in the covalent attachment process,
      providing a universal mechanism of attachment for all proteins. The native
      conformation of attached protein is retained due to hydrophilic interactions in
      the interface region. The enzymatic activity of covalently attached protein
      remained high. The long-term activity of the modified layer to attach protein is
      explained by stabilisation of unpaired electrons in sp(2) carbon structures. A
      high concentration of free radicals can give multiple covalent bonds to the
      protein molecule and destroy the native conformation and with it the catalytic
      activity. The universal mechanism of protein attachment to free radicals could be
      extended to various methods of radiation damage of polymers. 

PMID- 24278664
TI  - The molecular genetics and cellular mechanisms underlying pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is an incurable disorder clinically
      characterised by a sustained elevation of mean arterial pressure in the absence
      of systemic involvement. As the adult circulation is a low pressure, low
      resistance system, PAH represents a reversal to a foetal state. The small
      pulmonary arteries of patients exhibit luminal occlusion resultant from the
      uncontrolled growth of endothelial and smooth muscle cells. This vascular
      remodelling is comprised of hallmark defects, most notably the plexiform lesion.
      PAH may be familial in nature but the majority of patients present with
      spontaneous disease or PAH associated with other complications. In this paper,
      the molecular genetic basis of the disorder is discussed in detail ranging from
      the original identification of the major genetic contributant to PAH and moving
      on to current next-generation technologies that have led to the rapid
      identification of additional genetic risk factors. The impact of identified
      mutations on the cell is examined, particularly, the determination of pathways
      disrupted in disease and critical to pulmonary vascular maintenance. Finally, the
      application of research in this area to the design and development of novel
      treatment options for patients is addressed along with the future directions PAH
      research is progressing towards. 

PMID- 24278666
TI  - Large-scale survey of unselected automated visual fields in a major reading
      center: patterns and data analysis.
AB  - A prospective, randomized study was conducted to survey a large number of
      automated perimetry examinations in a central reading institute, obtaining
      practical information on unselected referred patients and their clinician
      "consumers". Visual field records of 1041 patients were obtained, each evaluated
      by one of three glaucoma specialists. Statistical analysis was applied on
      demographics, physician characteristics, test reliability and visual field
      scores. Reliability was scored on a scale of 1 (excellent) to 5
      (uninterpretable). Data from earlier examinations of these patients was also
      analyzed. The large majority of patients (70.4%) were referred due to glaucoma,
      ocular hypertension or suspected glaucoma. Most of the patients had threshold
      strategies: FastPac 24-2 or 30-2 (88.9%), Full Threshold (0.7%), and 10-2 (0.5%).
      In only 7 patients was short-wavelength automated perimetry (SWAP) performed. The
      Swedish Interactive Testing Algorithm (SITA) was applied in 1.0% of cases. More
      than half (56.8%) of the population had a reliability score of 1, and 22.7% had a
      score of 2, indicating a valid result for 79.4% of patients, providing clinically
      useful information. Linear regression analyses indicated that the Mean Defect was
      a better predictor of the visual field score than the Corrected Pattern Standard
      Deviation (CPSD), for the entire group and for each visual field score subgroup. 

PMID- 24278667
TI  - Hepatitis C virus, cryoglobulinemia, and kidney: novel evidence.
AB  - Hepatitis C virus infection can lead to chronic active hepatitis, cirrhosis, and
      liver failure; however, it is also associated with a wide range of extra-hepatic
      complications. HCV is associated with a large spectrum of histopathological
      lesions in both native and transplanted kidneys, and it is increasingly
      recognized as an instigator of B cell lympho-proliferative disorders including
      mixed cryoglobulinemia. Mixed cyoglobulinemia is a systemic vasculitis primarily
      mediated by immune complexes; it is characterized by variable organ involvement
      including skin lesions, chronic hepatitis, glomerulonephritis, peripheral
      neuropathy, and arthralgias. The most frequent HCV-associated nephropathy is type
      I membranoproliferative glomerulonephritis, usually in the context of type II
      mixed cryoglobulinemia. Various approaches have been tried for the treatment of
      HCV-related glomerulonephritis, including immunosuppressive therapy
      (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents.
      Data on the antiviral treatment of HCV-associated glomerulonephritis are not
      abundant but encouraging results have been provided. Immunosuppressive therapy is
      particularly recommended for cryoglobulinemic kidney disease. Recent evidence has
      been accumulated on rituximab therapy for HCV-related cryoglobulinemic
      glomerulonephritis exists but several questions related to its use remain
      unclear. Distinct approaches should be considered for the treatment of HCV
      associated cryoglobulinemic glomerulonephritis according to the level of
      proteinuria and kidney failure. 

PMID- 24278668
TI  - Adjudication of the alleged role of vitamin d in the antimicrobial pathway.
AB  - Dynamic interactions between microorganism and host have evolved in such a way
      that while microbial pathogens are the cause of many human infections, a
      symbiotic relationship is also known to exist. Another important anomaly is that
      exposure to pathogenic organisms does not necessarily result in development of
      clinical disease. The latter conclusion infers that susceptibility to infectious
      disease can be modified by host-related factors. Arguably the two most prominent
      factors are genetic variability and immunologic status of the exposed individual.
      Because of the Human Genome and the HapMap projects, developments in genotyping
      technology have brought the possibility of identifying associations between
      specific genetic alterations and common diseases closer to reality. In addition,
      a growing body of evidence suggests vitamin D has an important contributory role
      in the antimicrobial pathway. 

PMID- 24278670
TI  - Homeostatic imbalance in epithelial ducts and its role in carcinogenesis.
AB  - An epithelial duct is a well-defined multicellular structure composed of tightly
      packed cells separating and protecting body compartments that are used for enzyme
      secretion and its transport across the internal. The structural and functional
      integrity (homeostasis) of such ducts is vital in carrying many life functions
      (breathing, lactation, production of hormones). However, the processes involved
      in maintaining the homeostatic balance are not yet fully understood. On the other
      hand, the loss of epithelial tissue architecture, such as filled lumens or ductal
      disorganization, are among the first symptoms of the emerging epithelial tumors
      (carcinomas). Using the previously developed biomechanical model of epithelial
      ducts: IBCell, we investigated how different signals and mechanical stimuli
      imposed on individual epithelial cells can impact the homeostatic (im)balance and
      integrity of the whole epithelial tissue. We provide a link between erroneous
      responses of individual epithelial cells to specific signals and the emerging
      ductal morphologies characteristic for preinvasive cancers observed in pathology
      specimens, or characteristic for multicellular structures arising from mutated
      cells cultured in vitro. We summarize our finding in terms of altered properties
      of epithelial cell polarization, and discuss the relative importance of various
      polarization signals on the formation of tumor-like multicellular structures. 

PMID- 24278669
TI  - Using risk models to improve patient selection for high-risk vascular surgery.
AB  - Vascular surgeons frequently perform procedures aimed at limiting death, stroke,
      or amputation on patients who present with diseases such as aortic aneurysms,
      carotid atherosclerosis, and peripheral arterial occlusive disease. However, now
      more than ever surgeons must balance the potential benefits associated with these
      interventions with the risks of physiologic insult for these elderly patients,
      who often have significant comorbidity burdens and the potential for costly
      complications. In this paper, we highlight how regional and national datasets can
      help surgeons identify which patients are most likely to benefit from vascular
      operations and which patients are most likely to suffer complications in the
      postoperative period. By using these guidelines to improve patient selection, our
      risk models can help patients, physicians, and policymakers improve the clinical
      effectiveness of surgical and endovascular treatments for vascular disease. 

PMID- 24278671
TI  - Within-niche constant selection of Drosophila inversions?
AB  - Extensive and fruitful work is being devoted for more than 70 years to elucidate
      the fine points of the maintenance of inversion polymorphisms of the genus
      Drosophila. Recent studies have resumed selection in heterogeneous environments
      (or niches) as a major underlying mechanism for these balanced polymorphisms. In
      those studies, constant selection within niches is assumed throughout although
      this assumption is since long known not to hold. In the present communication it
      is sustained that the results in those studies are robust in the face of this
      fact. To that end, this communication deals with a particular long-lasting
      question within this topic-whether the minimal model of constant viability
      selection (MCV, assuming frequency-, sex-, and stage-independent adaptive values)
      suffices to reproduce the trajectories of frequencies of Drosophila chromosomal
      arrangements observed in experimental populations along generations under
      homogeneous environments. Fitness estimates are here obtained from published
      trajectories of frequencies using a maximum likelihood approach, and relevant
      literature is revised in the light of these new analyses, pointing to an
      affirmative answer to that question. 

PMID- 24278672
TI  - Genetic aspects of congenital and idiopathic scoliosis.
AB  - Congenital and idiopathic scoliosis represent disabling conditions of the spine.
      While congenital scoliosis (CS) is caused by morphogenic abnormalities in
      vertebral development, the cause(s) for idiopathic scoliosis is (are) likely to
      be varied, representing alterations in skeletal growth, neuromuscular imbalances,
      disturbances involving communication between the brain and spine, and others.
      Both conditions are characterized by phenotypic and genetic heterogeneities,
      which contribute to the difficulties in understanding their genetic basis that
      investigators face. Despite the differences between these two conditions there is
      observational and experimental evidence supporting common genetic mechanisms.
      This paper focuses on the clinical features of both CS and IS and highlights
      genetic and environmental factors which contribute to their occurrence. It is
      anticipated that emerging genetic technologies and improvements in phenotypic
      stratification of both conditions will facilitate improved understanding of the
      genetic basis for these conditions and enable targeted prevention and treatment
      strategies. 

PMID- 24278673
TI  - Neuroimaging and neurocognitive correlates of aggression and violence in
      schizophrenia.
AB  - Individuals diagnosed with major mental disorders such as schizophrenia are more
      likely to have engaged in violent behavior than mentally healthy members of the
      same communities. Although aggressive acts can have numerous causes, research
      about the underlying neurobiology of violence and aggression in schizophrenia can
      lead to a better understanding of the heterogeneous nature of that behavior and
      can assist in developing new treatment strategies. The purpose of this paper is
      to review the recent literature and discuss some of the neurobiological
      correlates of aggression and violence. The focus will be on schizophrenia, and
      the results of neuroimaging and neuropsychological studies that have directly
      investigated brain functioning and/or structure in aggressive and violent samples
      will be discussed as well as other domains that might predispose to aggression
      and violence such as deficits in responding to the emotional expressions of
      others, impulsivity, and psychopathological symptoms. Finally gender differences
      regarding aggression and violence are discussed. In this context several
      methodological and conceptional issues that limited the comparison of these
      studies will be addressed. 

PMID- 24278674
TI  - Role of hydrogen sulfide in the pathology of inflammation.
AB  - Hydrogen sulfide (H2S) is a well-known toxic gas that is synthesized in the human
      body from the amino acids cystathionine, homocysteine, and cysteine by the action
      of at least two distinct enzymes: cystathionine-gamma-lyase and cystathionine
      beta-synthase. In the past few years, H2S has emerged as a novel and increasingly
      important biological mediator. Imbalances in H2S have also been shown to be
      associated with various disease conditions. However, defining the precise
      pathophysiology of H2S is proving to be a complex challenge. Recent research in
      our laboratory has shown H2S as a novel mediator of inflammation and work in
      several groups worldwide is currently focused on determining the role of H2S in
      inflammation. H2S has been implicated in different inflammatory conditions, such
      as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive
      pulmonary disease (COPD). Active research on the role of H2S in inflammation will
      unravel the pathophysiology of its actions in inflammatory conditions and may
      help develop novel therapeutic approaches for several, as yet incurable, disease
      conditions. 

PMID- 24278675
TI  - Role of angiopoietin/tie2 in critical illness: promising biomarker, disease
      mediator, and therapeutic target?
AB  - Critical illness is a descriptive, broad term for a serious clinical condition
      that can result from enormously heterogeneous etiologies. A common end feature
      these patients regularly suffer from is the so-called multiple organ dysfunction
      syndrome (MODS), often a consequence of organ hypoperfusion and ischemia,
      coagulopathies, overwhelming inflammatory responses, immune paralysis and
      mitochondrial dysfunction. Mechanistically, endothelial injury and particularly
      microvascular leakage is a major step in the pathophysiology of MODS and
      contributes to its mortality. The angiopoietin (Angpt)/Tie2 system consists of
      the endothelial tyrosine kinase Tie2 and its 4 circulating ligands (Angpt1-4).
      The balance between the agonistic ligand "Angpt-1" and the antagonistic one
      "Angpt-2" regulates baseline endothelial barrier function and its response to
      injury and is therefore considered a gatekeeper of endothelial activation. This
      paper provides a systematic overview of the Angpt/Tie2 system with respect to (1)
      its role as a global biomarker of endothelial activation in critical ill
      patients, (2) its contribution to MODS pathophysiology as a disease mediator, and
      last but not least (3) putative therapeutic applications to modify the activation
      state of Tie2 in mice and men. 

PMID- 24278678
TI  - Congenital pulmonary malformation in children.
AB  - Congenital Pulmonary Malformations (CPMs) are a group of rare lung abnormalities
      affecting the airways, parenchyma, and vasculature. They represent a spectrum of
      abnormal development rather than discrete pathological entities. They are caused
      by aberrant embryological lung development which occurs at different stages of
      intrauterine life. 

PMID- 24278677
TI  - Stress in obesity and associated metabolic and cardiovascular disorders.
AB  - Obesity has significant implications for healthcare, since it is a major risk
      factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a
      common and complex disorder combining obesity, dyslipidemia, hypertension, and
      insulin resistance. It is associated with high atherosclerotic cardiovascular
      risk, which can only partially be explained by its components. Therefore, to
      explain how obesity contributes to the development of metabolic and
      cardiovascular disorders, more and better insight is required into the effects of
      personal and environmental stress on disease processes. In this paper, we show
      that obesity is a chronic inflammatory disease, which has many molecular
      mechanisms in common with atherosclerosis. Furthermore, we focus on the role of
      oxidative stress associated with obesity in the development of the metabolic
      syndrome. We discuss how several stress conditions are related to inflammation
      and oxidative stress in association with obesity and its complications. We also
      emphasize the relation between stress conditions and the deregulation of
      epigenetic control mechanisms by means of microRNAs and show how this impairment
      further contributes to the development of obesity, closing the vicious circle.
      Finally, we discuss the limitations of current anti-inflammation and antioxidant
      therapy to treat obesity. 

PMID- 24278676
TI  - Pathology-dependent effects linked to small heat shock proteins expression: an
      update.
AB  - Small heat shock proteins (small Hsps) are stress-induced molecular chaperones
      that act as holdases towards polypeptides that have lost their folding in stress
      conditions or consequently of mutations in their coding sequence. A cellular
      protection against the deleterious effects mediated by damaged proteins is thus
      provided to cells. These chaperones are also highly expressed in response to
      protein conformational and inflammatory diseases and cancer pathologies. Through
      specific and reversible modifications in their phospho-oligomeric organization,
      small Hsps can chaperone appropriate client proteins in order to provide cells
      with resistance to different types of injuries or pathological conditions. By
      helping cells to better cope with their pathological status, their expression can
      be either beneficial, such as in diseases characterized by pathological cell
      degeneration, or deleterious when they are required for tumor cell survival.
      Moreover, small Hsps are actively released by cells and can act as immunogenic
      molecules that have dual effects depending on the pathology. The cellular
      consequences linked to their expression levels and relationships with other Hsps
      as well as therapeutic strategies are discussed in view of their dynamic
      structural organization required to interact with specific client polypeptides. 

PMID- 24278679
TI  - The Need for Development of New HIV-1 Reverse Transcriptase and Integrase
      Inhibitors in the Aftermath of Antiviral Drug Resistance.
AB  - The use of highly active antiretroviral therapy (HAART) involves combinations of
      drugs to achieve maximal virological response and reduce the potential for the
      emergence of antiviral resistance. There are two broad classes of reverse
      transcriptase inhibitors, the nucleoside reverse transcriptase inhibitors (NRTIs)
      and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Since the first
      classes of such compounds were developed, viral resistance against them has
      necessitated the continuous development of novel compounds within each class.
      This paper considers the NRTIs and NNRTIs currently in both preclinical and
      clinical development or approved for second line therapy and describes the
      patterns of resistance associated with their use, as well as the underlying
      mechanisms that have been described. Due to reasons of both affordability and
      availability, some reverse transcriptase inhibitors with low genetic barrier are
      more commonly used in resource-limited settings. Their use results to the
      emergence of specific patterns of antiviral resistance and so may require
      specific actions to preserve therapeutic options for patients in such settings.
      More recently, the advent of integrase strand transfer inhibitors represents
      another major step forward toward control of HIV infection, but these compounds
      are also susceptible to problems of HIV drug resistance. 

PMID- 24278680
TI  - The genetics of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive, neurodegenerative disease that represents a
      growing global health crisis. Two major forms of the disease exist: early onset
      (familial) and late onset (sporadic). Early onset Alzheimer's is rare, accounting
      for less than 5% of disease burden. It is inherited in Mendelian dominant fashion
      and is caused by mutations in three genes (APP, PSEN1, and PSEN2). Late onset
      Alzheimer's is common among individuals over 65 years of age. Heritability of
      this form of the disease is high (79%), but the etiology is driven by a
      combination of genetic and environmental factors. A large number of genes have
      been implicated in the development of late onset Alzheimer's. Examples that have
      been confirmed by multiple studies include ABCA7, APOE, BIN1, CD2AP, CD33, CLU,
      CR1, EPHA1, MS4A4A/MS4A4E/MS4A6E, PICALM, and SORL1. Despite tremendous progress
      over the past three decades, roughly half of the heritability for the late onset
      of the disease remains unidentified. Finding the remaining genetic factors that
      contribute to the development of late onset Alzheimer's disease holds the
      potential to provide novel targets for treatment and prevention, leading to the
      development of effective strategies to combat this devastating disease. 

PMID- 24278681
TI  - Chronic heart failure: we are fighting the battle, but are we winning the war?
AB  - Heart failure represents an end-stage phenotype of a number of cardiovascular
      diseases and is generally associated with a poor prognosis. A number of organized
      battles fought over the last two to three decades have resulted in considerable
      advances in treatment including the use of drugs that interfere with
      neurohormonal activation and device-based therapies such as implantable
      cardioverter defibrillators and cardiac resynchronization therapy. Despite this,
      the prevalence of heart failure continues to rise related to both the aging
      population and better survival in patients with cardiovascular disease.
      Registries have identified treatment gaps and variation in the application of
      evidenced-based practice, including the use of echocardiography and prescribing
      of disease-modifying drugs. Quality initiatives often coupled with
      multidisciplinary, heart failure disease management promote self-care and
      minimize variation in the application of evidenced-based practice leading to
      better long-term clinical outcomes. However, to address the rising prevalence of
      heart failure and win the war, we must also turn our attention to disease
      prevention. A combined approach is required that includes public health measures
      applied at a population level and screening strategies to identify individuals at
      high risk of developing heart failure in the future. 

PMID- 24278682
TI  - Diabetes technology: markers, monitoring, assessment, and control of blood
      glucose fluctuations in diabetes.
AB  - People with diabetes face a life-long optimization problem: to maintain strict
      glycemic control without increasing their risk for hypoglycemia. Since the
      discovery of insulin in 1921, the external regulation of diabetes by engineering
      means has became a hallmark of this optimization. Diabetes technology has
      progressed remarkably over the past 50 years-a progress that includes the
      development of markers for diabetes control, sophisticated monitoring techniques,
      mathematical models, assessment procedures, and control algorithms. Continuous
      glucose monitoring (CGM) was introduced in 1999 and has evolved from means for
      retroactive review of blood glucose profiles to versatile reliable devices, which
      monitor the course of glucose fluctuations in real time and provide interactive
      feedback to the patient. Technology integrating CGM with insulin pumps is now
      available, opening the field for automated closed-loop control, known as the
      artificial pancreas. Following a number of in-clinic trials, the quest for a
      wearable ambulatory artificial pancreas is under way, with a first prototype
      tested in outpatient setting during the past year. This paper discusses key
      milestones of diabetes technology development, focusing on the progress in the
      past 10 years and on the artificial pancreas-still not a cure, but arguably the
      most promising treatment of diabetes to date. 

PMID- 24278683
TI  - Kinome profiling.
AB  - The use of arrays in genomics has led to a fast and reliable way to screen the
      transcriptome of an organism. It can be automated and analysis tools have become
      available and hence the technique has become widely used within the past few
      years. Signal-transduction routes rely mainly on the phosphorylation status of
      already available proteins; therefore kinases are central players in signal
      transduction routes. The array technology can now also be used for the analysis
      of the kinome. To enable array analysis, consensus peptides for kinases are spot
      on a solid support. After incubation with cell lysates and in the presence of
      radioactive ATP, radioactive peptides can be visualized and the kinases that are
      active in the cells can be determined. The present paper reviews comprehensively
      the different kinome array platforms available and results obtained hitherto
      using such platforms. It will appear that this technology does not disappoint its
      high expectations and is especially powerful because of its species independence.
      Nevertheless, improvements are still possible and I shall also sketch future
      possible directions. 

PMID- 24278685
TI  - Hemolytic uremic syndrome: late renal injury and changing incidence-a single
      centre experience in Canada.
AB  - Aims. To assess trends in the incidence of pediatric diarrhea-associated
      hemolytic uremic syndrome (D(+) HUS) and document long-term renal sequelae.
      Methods. We conducted a retrospective cohort study of children with D(+) HUS
      admitted to a tertiary care pediatric hospital in Montreal, Canada, from 1976 to
      2010. In 2010, we recontacted patients admitted before 2000. Results. Of 337
      cases, median age at presentation was 3.01 years (range 0.4-14). Yearly incidence
      peaked in 1988 and 1994-95, returning to near-1977 levels since 2003. Twelve
      patients (3.6%) died and 19 (5.6%) experienced long-term renal failure. Almost
      half (47%) The patients required dialysis. Need for dialysis was the best
      predictor of renal sequelae, accounting for 100% of severe complications. Of
      children followed >=1 year (n = 199, mean follow-up 8.20 +/- 6.78 years), 19 had
      severe and 18 mild-to-moderate kidney injury, a total sequelae rate, of 18.6%.
      Ten years or more after-HUS (n = 85, mean follow-up 15.4 +/- 5.32 years), 8
      (9.4%) patients demonstrated serious complications and 22 (25.9%) mild-to
      moderate, including 14 (16%) microalbuminuria: total sequelae, 35.3%.
      Conclusions. Patients with D(+) HUS should be monitored at least 5 years,
      including microalbuminuria testing, especially if dialysis was required. The
      cause of the declining incidence of D(+)HUS is elusive. However, conceivably,
      improved public health education may have played an important role in the
      prevention of food-borne disease. 

PMID- 24278684
TI  - Endometriosis, angiogenesis and tissue factor.
AB  - Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to
      initiate the blood coagulation cascade. In addition to its role as the initiator
      of the hemostatic cascade, TF is known to be involved in angiogenesis via
      intracellular signaling that utilizes the protease activated receptor-2 (PAR-2).
      We now review the physiologic expression of TF in the endometrium and its altered
      expression in multiple cell types derived from eutopic and ectopic endometrium
      from women with endometriosis compared with normal endometrium. Our findings
      suggest that TF might be an ideal target for therapeutic intervention in
      endometriosis. We have employed a novel immunoconjugate molecule known as Icon
      and were able to eradicate endometrial lesions in a mouse model of endometriosis
      without affecting fertility. These findings have major implications for potential
      treatment in humans. 

PMID- 24278686
TI  - Respiratory physiology on a chip.
AB  - Our current understanding of respiratory physiology and pathophysiological
      mechanisms of lung diseases is often limited by challenges in developing in vitro
      models faithful to the respiratory environment, both in cellular structure and
      physiological function. The recent establishment and adaptation of microfluidic
      based in vitro devices (MUFIVDs) of lung airways have enabled a wide range of
      developments in modern respiratory physiology. In this paper, we address recent
      efforts over the past decade aimed at advancing in vitro models of lung structure
      and airways using microfluidic technology and discuss their applications. We
      specifically focus on MUFIVDs covering four major areas of respiratory
      physiology, namely, artificial lungs (AL), the air-liquid interface (ALI), liquid
      plugs and cellular injury, and the alveolar-capillary barrier (ACB). 

PMID- 24278689
TI  - TRPM7 and TRPM8 Ion Channels in Pancreatic Adenocarcinoma: Potential Roles as
      Cancer Biomarkers and Targets.
AB  - Transient receptor potential (TRP) ion channels are essential for normal
      functions and health by acting as molecular sensors and transducing various
      stimuli into cellular and physiological responses. Growing evidence has revealed
      that TRP ion channels play important roles in a wide range of human diseases,
      including malignancies. In light of recent discoveries, it has been found that
      TRP melastatin-subfamily members, TRPM7 and TRPM8, are required for normal and
      cancerous development of exocrine pancreas. We are currently investigating the
      mechanisms which mediate the functional roles of TRPM7 and TRPM8 and attempting
      to develop these ion channels as clinical biomarkers and therapeutic targets for
      achieving the goal of personalized therapy in pancreatic cancer. 

PMID- 24278687
TI  - Recurrent venous thromboembolism: what is the risk and how to prevent it.
AB  - Venous thromboembolism (VTE) that includes deep vein thrombosis and/or pulmonary
      embolism is a frequent, severe, and potentially lethal disease. After a first
      episode, VTE has a strong tendency to recur. While VTE is an acute disease, it
      may have variable outcomes in early and late phases after initial presentation.
      Furthermore, the incidence of late, clinically important consequences
      (postthrombotic syndrome and/or chronic thromboembolic pulmonary hypertension)
      increases in case of recurrent events. The aims of the present review are (i) to
      analyze the incidence and risk factors for recurrence of VTE (either those
      related to the type of first thrombotic event or to the patients), the risks
      associated with occurrence of recurrent events, and the problems linked to the
      diagnosis, not always easy, of recurrent events; (ii) to discuss whether or not
      it is possible to predict the individual risk of recurrence after a first event,
      by stratifying patients at high or low risk of recurrence, and how this can
      influence their treatment; (iii) to comment what the current guidelines and
      guidance suggest/recommend about anticoagulant treatment after a first VTE event
      and, finally, to propose practical indications on how to manage individual
      patients affected by VTE. 

PMID- 24278688
TI  - Complement activation: an emerging player in the pathogenesis of cardiovascular
      disease.
AB  - A wealth of evidence indicates a fundamental role for inflammation in the
      pathogenesis of cardiovascular disease (CVD), contributing to the development and
      progression of atherosclerotic lesion formation, plaque rupture, and thrombosis.
      An increasing body of evidence supports a functional role for complement
      activation in the pathogenesis of CVD through pleiotropic effects on endothelial
      and haematopoietic cell function and haemostasis. Prospective and case control
      studies have reported strong relationships between several complement components
      and cardiovascular outcomes, and in vitro studies and animal models support a
      functional effect. Complement activation, in particular, generation of C5a and
      C5b-9, influences many processes involved in the development and progression of
      atherosclerosis, including promotion of endothelial cell activation, leukocyte
      infiltration into the extracellular matrix, stimulation of cytokine release from
      vascular smooth muscle cells, and promotion of plaque rupture. Complement
      activation also influences thrombosis, involving components of the mannose
      binding lectin pathway, and C5b-9 in particular, through activation of platelets,
      promotion of fibrin formation, and impairment of fibrinolysis. The participation
      of the complement system in inflammation and thrombosis is consistent with the
      physiological role of the complement system as a rapid effector system conferring
      protection following vessel injury. However, in the context of CVD, these same
      processes contribute to development of atherosclerosis, plaque rupture, and
      thrombosis. 

PMID- 24278690
TI  - Nutritional modulation of insulin resistance.
AB  - Insulin resistance has been proposed as the strongest single predictor for the
      development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food,
      together with inadequate physical activity, have been recognized as the most
      relevant factors leading to overweight, abdominal adiposity, insulin resistance,
      and finally T2DM. Conversely, energy reduced diets almost invariably to
      facilitate weight loss and reduce abdominal fat mass and insulin resistance.
      However, sustained weight loss is generally difficult to achieve, and distinct
      metabolic characteristics in patients with T2DM further compromise success.
      Therefore, investigating the effects of modulating the macronutrient composition
      of isoenergetic diets is an interesting concept that may lead to additional
      important insights. Metabolic effects of various different dietary concepts and
      strategies have been claimed, but results from randomized controlled studies and
      particularly from longer-term-controlled interventions in humans are often
      lacking. However, some of these concepts are supported by recent research, at
      least in animal models and short-term studies in humans. This paper provides an
      update of the current literature regarding the role of nutrition in the
      modulation of insulin resistance, which includes the discussion of weight-loss
      independent metabolic effects of commonly used dietary concepts. 

PMID- 24278692
TI  - The visual effects of intraocular colored filters.
AB  - Modern life is associated with a myriad of visual problems, most notably
      refractive conditions such as myopia. Human ingenuity has addressed such problems
      using strategies such as spectacle lenses or surgical correction. There are other
      visual problems, however, that have been present throughout our evolutionary
      history and are not as easily solved by simply correcting refractive error. These
      problems include issues like glare disability and discomfort arising from
      intraocular scatter, photostress with the associated transient loss in vision
      that arises from short intense light exposures, or the ability to see objects in
      the distance through a veil of atmospheric haze. One likely biological solution
      to these more long-standing problems has been the use of colored intraocular
      filters. Many species, especially diurnal, incorporate chromophores from numerous
      sources (e.g., often plant pigments called carotenoids) into ocular tissues to
      improve visual performance outdoors. This review summarizes information on the
      utility of such filters focusing on chromatic filtering by humans. 

PMID- 24278691
TI  - Gastroparesis: concepts, controversies, and challenges.
AB  - Patients with gastroparesis often present a challenge to the treating physician.
      Postprandial symptoms with nausea and vomiting may not only lead to nutritional
      and metabolic consequences, but also cause significant disruptions to social
      activities that often center around food. While the definition of gastroparesis
      focuses on impaired gastric emptying, treatment options that affect gastric
      function are limited and often disappointing. The female predominance, the mostly
      idiopathic nature of the illness with a common history of abuse, and coexisting
      anxiety or depression show parallels with other functional disorders of the
      gastrointestinal tract. These parallels provided the rationale for some initial
      studies investigating alternative therapies that target the brain rather than the
      stomach. This emerging shift in medical therapy comes at a time when clinical
      studies suggest that gastric electrical stimulation may exert its effects by
      modulating visceral sensory processing rather than altering gastric motility.
      Physiologic and detailed anatomic investigations also support a more complex
      picture with different disease mechanisms, ranging from impaired accommodation to
      apparent visceral hypersensitivity or decreased interstitial cells of Cajal to
      inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains
      the endophenotype defining gastroparesis. However, our treatment options go
      beyond prokinetics and may allow us to improve the quality of life of affected
      individuals. 

PMID- 24278693
TI  - Plasma membrane transporters in modern liver pharmacology.
AB  - The liver plays a crucial role in the detoxification of drugs used in the
      treatment of many diseases. The liver itself is the target for drugs aimed to
      modify its function or to treat infections and tumours affecting this organ. Both
      detoxification and pharmacological processes occurring in the liver require the
      uptake of the drug by hepatic cells and, in some cases, the elimination into
      bile. These steps have been classified as detoxification phase 0 and phase III,
      respectively. Since most drugs cannot cross the plasma membrane by simple
      diffusion, the involvement of transporters is mandatory. Several members of the
      superfamilies of solute carriers (SLC) and ATP-binding cassette (ABC) proteins,
      with a minor participation of other families of transporters, account for the
      uptake and efflux, respectively, of endobiotic and xenobiotic compounds across
      the basolateral and apical membranes of hepatocytes and cholangiocytes. These
      transporters are also involved in the sensitivity and refractoriness to the
      pharmacological treatment of liver tumours. An additional interesting aspect of
      the role of plasma membrane transporters in liver pharmacology regards the
      promiscuity of many of these carriers, which accounts for a variety of drug-drug,
      endogenous substances-drug and food components-drug interactions with clinical
      relevance. 

PMID- 24278694
TI  - The impact of primary care: a focused review.
AB  - Primary care serves as the cornerstone in a strong healthcare system. However, it
      has long been overlooked in the United States (USA), and an imbalance between
      specialty and primary care exists. The objective of this focused review paper is
      to identify research evidence on the value of primary care both in the USA and
      internationally, focusing on the importance of effective primary care services in
      delivering quality healthcare, improving health outcomes, and reducing
      disparities. Literature searches were performed in PubMed as well as
      "snowballing" based on the bibliographies of the retrieved articles. The areas
      reviewed included primary care definitions, primary care measurement, primary
      care practice, primary care and health, primary care and quality, primary care
      and cost, primary care and equity, primary care and health centers, and primary
      care and healthcare reform. In both developed and developing countries, primary
      care has been demonstrated to be associated with enhanced access to healthcare
      services, better health outcomes, and a decrease in hospitalization and use of
      emergency department visits. Primary care can also help counteract the negative
      impact of poor economic conditions on health. 

PMID- 24278695
TI  - Contemporary evaluation and management of the diabetic foot.
AB  - Foot problems in patients with diabetes remain a major public health issue and
      are the commonest reason for hospitalization of patients with diabetes with
      prevalence as high as 25%. Ulcers are breaks in the dermal barrier with
      subsequent erosion of underlying subcutaneous tissue that may extend to muscle
      and bone, and superimposed infection is a frequent and costly complication. The
      pathophysiology of diabetic foot disease is multifactorial and includes
      neuropathy, infection, ischemia, and abnormal foot structure and biomechanics.
      Early recognition of the etiology of these foot lesions is essential for good
      functional outcome. Managing the diabetic foot is a complex clinical problem
      requiring a multidisciplinary collaboration of health care workers to achieve
      limb salvage. Adequate off-loading, frequent debridement, moist wound care,
      treatment of infection, and revascularization of ischemic limbs are the mainstays
      of therapy. Even when properly managed, some of the foot ulcers do not heal and
      are arrested in a state of chronic inflammation. These wounds can frequently
      benefit from various adjuvants, such as aggressive debridement, growth factors,
      bioactive skin equivalents, and negative pressure wound therapy. While these,
      increasingly expensive, therapies have shown promising results in clinical
      trials, the results have yet to be translated into widespread clinical practice
      leaving a huge scope for further research in this field. 

PMID- 24278696
TI  - Genome-scale technology driven advances to research into normal and malignant
      haematopoiesis.
AB  - Haematopoiesis or blood development has long served as a model system for adult
      stem cell biology. Moreover, when combined, the various cancers of the blood
      represent one of the commonest human malignancies. Large numbers of researchers
      have therefore dedicated their scientific careers to studying haematopoiesis for
      more than a century. Throughout this period, many new technologies have first
      been applied towards the study of blood cells, and the research fields of normal
      and malignant haematopoiesis have also been some of the earliest adopters of
      genome-scale technologies. This has resulted in significant new insights with
      implications ranging from basic biological mechanisms to patient diagnosis and
      prognosis and also produced lessons likely to be relevant for many other areas of
      biomedical research. This paper discusses the current state of play for a range
      of genome-scale applications within haemopoiesis research, including gene
      expression profiling, ChIP-sequencing, genomewide association analysis, and
      cancer genome sequencing. A concluding outlook section explores likely future
      areas of progress as well as potential technological and educational bottlenecks.

PMID- 24278697
TI  - The Epstein-Barr Virus EBNA1 Protein.
AB  - Epstein-Barr virus (EBV) is a widespread human herpes virus that immortalizes
      cells as part of its latent infection and is a causative agent in the development
      of several types of lymphomas and carcinomas. Replication and stable persistence
      of the EBV genomes in latent infection require the viral EBNA1 protein, which
      binds specific DNA sequences in the viral DNA. While the roles of EBNA1 were
      initially thought to be limited to effects on the viral genomes, more recently
      EBNA1 has been found to have multiple effects on cellular proteins and pathways
      that may also be important for viral persistence. In addition, a role for EBNA1
      in lytic infection has been recently identified. The multiple roles of EBNA1 in
      EBV infection are the subject of this paper. 

PMID- 24278698
TI  - Membrane transporters as mediators of Cisplatin effects and side effects.
AB  - Transporters are important mediators of specific cellular uptake and thus, not
      only for effects, but also for side effects, metabolism, and excretion of many
      drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is
      limited by its severe acute and chronic nephro-, oto-, and peripheral
      neurotoxicity. For this reason, other platinum derivatives, such as carboplatin
      and oxaliplatin, with less toxicity but still with antitumoral action have been
      developed. Several transporters, which are expressed on the cell membranes, have
      been associated with cisplatin transport across the plasma membrane and across
      the cell: the copper transporter 1 (Ctr1), the copper transporter 2 (Ctr2), the P
      type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter
      2 (OCT2), and the multidrug extrusion transporter 1 (MATE1). Some of these
      transporters are also able to accept other platinum derivatives as substrate.
      Since membrane transporters display a specific tissue distribution, they can be
      important molecules that mediate the entry of platinum derivatives in target and
      also nontarget cells possibly mediating specific effects and side effects of the
      chemotherapeutic drug. This paper summarizes the literature on toxicities of
      cisplatin compared to that of carboplatin and oxaliplatin and the interaction of
      these platinum derivatives with membrane transporters. 

PMID- 24278699
TI  - Phylogenetic origins of brain organisers.
AB  - The regionalisation of the nervous system begins early in embryogenesis,
      concomitant with the establishment of the anteroposterior (AP) and dorsoventral
      (DV) body axes. The molecular mechanisms that drive axis induction appear to be
      conserved throughout the animal kingdom and may be phylogenetically older than
      the emergence of bilateral symmetry. As a result of this process, groups of
      patterning genes that are equally well conserved are expressed at specific AP and
      DV coordinates of the embryo. In the emerging nervous system of vertebrate
      embryos, this initial pattern is refined by local signalling centres, secondary
      organisers, that regulate patterning, proliferation, and axonal pathfinding in
      adjacent neuroepithelium. The main secondary organisers for the AP neuraxis are
      the midbrain-hindbrain boundary, zona limitans intrathalamica, and anterior
      neural ridge and for the DV neuraxis the notochord, floor plate, and roof plate.
      A search for homologous secondary organisers in nonvertebrate lineages has led to
      controversy over their phylogenetic origins. Based on a recent study in
      hemichordates, it has been suggested that the AP secondary organisers evolved at
      the base of the deuterostome superphylum, earlier than previously thought.
      According to this view, the lack of signalling centres in some deuterostome
      lineages is likely to reflect a secondary loss due to adaptive processes. We
      propose that the relative evolutionary flexibility of secondary organisers has
      contributed to a broader morphological complexity of nervous systems in different
      clades. 

PMID- 24278701
TI  - Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in
      Cortical Development and Disease.
AB  - During cortical development, proliferating neural progenitors exhibit polarized
      apical and basolateral membranes that are maintained by tightly controlled and
      membrane-specific vesicular trafficking pathways. Disruption of polarity through
      impaired delivery of proteins can alter cell fate decisions and consequent
      expansion of the progenitor pool, as well as impact the integrity of the
      neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial
      scaffolding and alters initial neuronal migration from the ventricular zone.
      Vesicle trafficking is also required for maintenance of lipid and protein cycling
      within the leading and trailing edge of migratory neurons, as well as dendrites
      and synapses of mature neurons. Defects in this transport machinery disrupt
      neuronal identity, migration, and connectivity and give rise to a malformation of
      cortical development termed as periventricular heterotopia (PH). PH is
      characterized by a reduction in brain size, ectopic clusters of neurons localized
      along the lateral ventricle, and epilepsy and dyslexia. These anatomical
      anomalies correlate with developmental impairments in neural progenitor
      proliferation and specification, migration from loss of neuroependymal integrity
      and neuronal motility, and aberrant neuronal process extension. Genes causal for
      PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network.
      This paper explores the role of these dynamic processes in cortical development
      and disease. 

PMID- 24278702
TI  - The complex interplay of genetic and lifestyle risk factors in type 2 diabetes:
      an overview.
AB  - Type 2 diabetes (T2D) is one of the scourges of modern times, with many millions
      of people affected by the disease. Diabetes occurs most frequently in those who
      are overweight or obese. However, not all overweight and obese persons develop
      diabetes, and there are those who develop the disease who are lean and physically
      active. Certain ethnicities, especially indigenous populations, are at
      considerably higher risk of obesity and diabetes than those of white European
      ancestry. The patterns and distributions of diabetes have led some to speculate
      that the disease is caused by interactions between genetic and obesogenic
      lifestyle factors. Whilst to many this is a plausible explanation, remarkably
      little reliable evidence exists to support it. In this review, an overview of
      published literature relating to genetic and lifestyle risk factors for T2D is
      provided. The review also describes the concepts and rationale that have
      motivated the view that gene-lifestyle interactions cause diabetes and overviews
      the empirical evidence published to date to support this hypothesis. 

PMID- 24278700
TI  - Direct acting antivirals for the treatment of chronic viral hepatitis.
AB  - The development and evaluation of antiviral agents through carefully designed
      clinical trials over the last 25 years have heralded a new dawn in the treatment
      of patients chronically infected with the hepatitis B and C viruses, but not so
      for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals
      (DDAs) for the treatment of HBV carriers has permitted the long-term use of these
      compounds for the continuous suppression of viral replication, whilst in the case
      of HCV in combination with the standard of care [SOC, pegylated interferon
      (PegIFN), and ribavirin] sustained virological responses (SVRs) have been
      achieved with increasing frequency. Progress in the case of HDV has been slow and
      lacking in significant breakthroughs.This paper aims to summarise the current
      state of play in treatment approaches for chonic viral hepatitis patients and
      future perspectives. 

PMID- 24278703
TI  - Established and emerging approaches for the management of dyslipidaemia.
AB  - The key role of dyslipidaemia in determining cardiovascular disease (CVD) has
      been proved beyond reasonable doubt, and therefore several dietary and
      pharmacological approaches have been developed. The discovery of statins has
      provided a very effective approach in reducing cardiovascular risk as documented
      by the results obtained in clinical trials and in clinical practice. The current
      efficacy of statins or other drugs, however, comes short of providing the benefit
      that could derive from a further reduction of LDL cholesterol (LDL-C) in high
      risk and very high risk patients. Furthermore, experimental data clearly suggest
      that other lipoprotein classes beyond LDL play important roles in determining
      cardiovascular risk. For these reasons a number of new potential drugs are under
      development in this area. Aim of this review is to discuss the available and the
      future pharmacological strategies for the management of dyslipidemia. 

PMID- 24278705
TI  - In search of an accurate evaluation of intrahepatic cholestasis of pregnancy.
AB  - Until now, biochemical parameter for diagnosis of intrahepatic cholestasis of
      pregnancy (ICP) mostly used is the rise of total serum bile acids (TSBA) above
      the upper normal limit of 11 MUM. However, differential diagnosis is very
      difficult since overlapped values calculated on bile acids determinations, are
      observed in different conditions of pregnancy including the benign condition of
      pruritus gravidarum. The aim of this work was to determine the better markers in
      ICP for a precise diagnosis together with parameters associated with severity of
      symptoms and treatment evaluation. Serum bile acid profiles were evaluated using
      capillary electrophoresis in 38 healthy pregnant women and 32 ICP patients and it
      was calculated the sensitivity, specificity, accuracy, predictive values and the
      relationships of certain individual bile acids in pregnant women in order to
      replace TSBA determinations. The evaluation of the results shows that LCA and
      UDCA/LCA ratio provided information for a more complete and accurate diagnosis
      and evaluation of ICP than calculation of solely TSBA levels in pregnant women. 

PMID- 24278704
TI  - Detection of microorganisms in granulomas that have been formalin-fixed: review
      of the literature regarding use of molecular methods.
AB  - Granuloma is an organized aggregate of immune cells that under the microscope
      appear as epithelioid macrophages. A granuloma can only be diagnosed when a
      pathologist observes this type of inflammation under the microscope. If a foreign
      body or a parasite is not observed inside the granuloma, stains for acid-fast
      bacilli and fungi are ordered since mycobacteria and fungi are frequently the
      cause of this type of inflammation. It is calculated that 12 to 36% of granulomas
      do not have a specific etiology and many have wondered if with new molecular
      methods we could reduce this number. This paper will summarize the frequently
      known causes of granulomas and will present the recent literature regarding the
      use of molecular techniques on tissue specimens and how these have helped in
      defining causative agents. We will also briefly describe new research regarding
      formation and function of granulomas and how this impacts our ability to find an
      etiologic agent. 

PMID- 24278706
TI  - New prospective for the management of low-risk pulmonary embolism: prognostic
      assessment, early discharge, and single-drug therapy with new oral
      anticoagulants.
AB  - Patients with pulmonary embolism (PE) can be stratified into two different
      prognostic categories, based on the presence or absence of shock or sustained
      arterial hypotension. Some patients with normotensive PE have a low risk of early
      mortality, defined as <1% at 30 days or during hospital stay. In this paper, we
      will discuss the new prospective for the optimal management of low-risk PE:
      prognostic assessment, early discharge, and single-drug therapy with new oral
      anticoagulants. Several parameters have been proposed and investigated to
      identify low-risk PE: clinical prediction rules, imaging tests, and laboratory
      markers of right ventricular dysfunction or injury. Moreover, outpatient
      management has been suggested for low-risk PE: it may lead to a decrease in
      unnecessary hospitalizations, acquired infections, death, and costs and to an
      improvement in health-related quality of life. Finally, the main characteristics
      of new oral anticoagulant drugs and the most recent published data on phase III
      trials on PE suggest that the single-drug therapy is a possible suitable option.
      Oral administration, predictable anticoagulant responses, and few drug-drug
      interactions of direct thrombin and factor Xa inhibitors may further simplify PE
      home therapy avoiding administration of low-molecular-weight heparin. 

PMID- 24278707
TI  - Finding the correct partner: the meiotic courtship.
AB  - Homologous chromosomes are usually separated at the entrance of meiosis; how they
      become paired is one of the outstanding mysteries of the meiotic process.
      Reduction of spacing between homologues makes possible the occurrence of
      chromosomal interactions leading to homology detection and the formation of
      bivalents. In many organisms, telomere-led chromosome movements are generated
      that bring homologues together. Additional movements produced by chromatin
      conformational changes at early meiosis may also facilitate homologous contacts.
      Organisms used in the study of meiosis show a surprising variety of strategies
      for homology detection. In dipterans, homologous chromosomes remain paired
      throughout most of development. Pairing seems to arise as a balance between
      promoter and suppressor pairing genes. Some fungi, plants and animals, use
      mechanisms based on recombinational interactions. Other mechanisms leading to
      homology search are recombination-independent and require specialized pairing
      sites. In the worm Caenorhabditis elegans, each chromosome carries a pairing
      center consisting of a chromosome-specific DNA-protein complex, and in the
      fission yeast Schizosaccharomyces pombe, the sme2 locus encodes a meiosis
      specific non-coding RNA that mediates on homologous recognition. In addition,
      mismatch correction plays a relevant role, especially in polyploids, which
      evolved genetic systems that suppress pairing between non-homologous related
      (homoeologus) chromosomes. 

PMID- 24278709
TI  - A comparison of two classes of methods for estimating false discovery rates in
      microarray studies.
AB  - The goal of many microarray studies is to identify genes that are differentially
      expressed between two classes or populations. Many data analysts choose to
      estimate the false discovery rate (FDR) associated with the list of genes
      declared differentially expressed. Estimating an FDR largely reduces to
      estimating pi 1, the proportion of differentially expressed genes among all
      analyzed genes. Estimating pi 1 is usually done through P-values, but computing P
      values can be viewed as a nuisance and potentially problematic step. We evaluated
      methods for estimating pi 1 directly from test statistics, circumventing the need
      to compute P-values. We adapted existing methodology for estimating pi 1 from t-
      and z-statistics so that pi 1 could be estimated from other statistics. We
      compared the quality of these estimates to estimates generated by two established
      methods for estimating pi 1 from P-values. Overall, methods varied widely in bias
      and variability. The least biased and least variable estimates of pi 1, the
      proportion of differentially expressed genes, were produced by applying the
      "convest" mixture model method to P-values computed from a pooled permutation
      null distribution. Estimates computed directly from test statistics rather than P
      values did not reliably perform well. 

PMID- 24278708
TI  - Regulatory mechanisms of injury and repair after hepatic ischemia/reperfusion.
AB  - Hepatic ischemia/reperfusion injury is an important complication of liver surgery
      and transplantation. The mechanisms of this injury as well as the subsequent
      reparative and regenerative processes have been the subject of thorough study. In
      this paper, we discuss the complex and coordinated responses leading to
      parenchymal damage after liver ischemia/reperfusion as well as the manner in
      which the liver clears damaged cells and regenerates functional mass. 

PMID- 24278710
TI  - Feminization of Longnose Dace (Rhinichthys cataractae) in the Oldman River,
      Alberta, (Canada) Provides Evidence of Widespread Endocrine Disruption in an
      Agricultural Basin.
AB  - We sampled an abundant, native minnow (Longnose dace-Rhinichthys cataractae)
      throughout the Oldman River, Alberta, to determine physiological responses and
      possible population level consequences from exposure to compounds with hormone
      like activity. Sex ratios varied between sites, were female-biased, and ranged
      from just over 50% to almost 90%. Histological examination of gonads revealed
      that at the sites with >60% females in the adult population, there was up to 38%
      occurrence of intersex gonads in fish identified through visual examination of
      the gonads as male. In the majority of intersex gonad cases, there was a large
      proportion (approx., 50%) of oocytes within the testicular tissue. In male dace,
      vitellogenin mRNA expression generally increased with distance downstream. We
      analyzed river water for 28 endocrine disrupting compounds from eight functional
      classes, most with confirmed estrogen-like activity, including synthetic
      estrogens and hormone therapy drugs characteristic of municipal wastewater
      effluent, plus natural hormones and veterinary pharmaceuticals characteristic of
      livestock production. The spatial correlation between detected chemical residues
      and effects to dace physiology indicate that multiple land uses have a cumulative
      impact on dace in the Oldman River and effects range from altered gene regulation
      to severely female-biased sex ratios. 

PMID- 24278711
TI  - The prothrombotic tendency in metabolic syndrome: focus on the potential
      mechanisms involved in impaired haemostasis and fibrinolytic balance.
AB  - The metabolic syndrome is a clinical disorder characterized by impairment of
      glucose metabolism, increased arterial blood pressure, and abdominal obesity. The
      presence of these clinical features exposes patients to a high risk of
      atherothrombotic cardiovascular events. The pathogenesis of atherothrombosis in
      the metabolic syndrome is multifactorial, requiring a close relationship among
      the main components of the metabolic syndrome, including insulin resistance,
      alterations of glycaemic and lipid pattern, haemodynamic impairment, and early
      appearance of endothelial dysfunction. Furthermore, haemostatic alterations
      involving coagulation balance, fibrinolysis, and platelet function play a
      relevant role both in the progression of the arterial wall damage and in acute
      vascular events. The mechanisms linking abdominal obesity with prothrombotic
      changes in the metabolic syndrome have been identified and partially elucidated
      on the basis of alterations of each haemostatic variable and defined through the
      evidence of peculiar dysfunctions in the endocrine activity of adipose tissue
      responsible of vascular impairment, prothrombotic tendency, and low-grade chronic
      inflammation. This paper will focus on the direct role of adipose tissue on
      prothrombotic tendency in patients affected by metabolic syndrome, with
      adipocytes being able to produce and/or release cytokines and adipokines which
      deeply influence haemostatic/fibrinolytic balance, platelet function, and
      proinflammatory state. 

PMID- 24278712
TI  - Marsupial genome sequences: providing insight into evolution and disease.
AB  - Marsupials (metatherians), with their position in vertebrate phylogeny and their
      unique biological features, have been studied for many years by a dedicated group
      of researchers, but it has only been since the sequencing of the first marsupial
      genome that their value has been more widely recognised. We now have genome
      sequences for three distantly related marsupial species (the grey short-tailed
      opossum, the tammar wallaby, and Tasmanian devil), with the promise of many more
      genomes to be sequenced in the near future, making this a particularly exciting
      time in marsupial genomics. The emergence of a transmissible cancer, which is
      obliterating the Tasmanian devil population, has increased the importance of
      obtaining and analysing marsupial genome sequence for understanding such diseases
      as well as for conservation efforts. In addition, these genome sequences have
      facilitated studies aimed at answering questions regarding gene and genome
      evolution and provided insight into the evolution of epigenetic mechanisms. Here
      I highlight the major advances in our understanding of evolution and disease,
      facilitated by marsupial genome projects, and speculate on the future
      contributions to be made by such sequences. 

PMID- 24278714
TI  - Regulation of inflammatory pathways in cancer and infectious disease of the
      cervix.
AB  - Cervical cancer is one of the leading gynaecological malignancies worldwide. It
      is an infectious disease of the cervix, associated with human papillomavirus
      infection (HPV), infection with bacterial agents such as Chlamydia trachomatis
      and Neisseria gonorrhoea as well as human immunodeficiency virus (HIV).
      Furthermore, it is an AIDS-defining disease with an accelerated mortality in HIV
      infected women with cervical cancer. With the introduction of robust vaccination
      strategies against HPV in the developed world, it is anticipated that the
      incidence of cervical cancer will decrease in the coming years. However,
      vaccination has limited benefit for women already infected with high-risk HPV,
      and alternative therapeutic intervention strategies are needed for these women.
      Many pathological disorders, including cervical cancer, are characterised by the
      exacerbated activation and maintenance of inflammatory pathways which are
      considered to be regulated by infectious agents. In cervical cancer,
      hyperactivation of these inflammatory pathways and regulation of immune
      infiltrate into tissues can potentially play a role not only in tumorigenesis but
      also in HIV infection. In this paper we will discuss the contribution of
      inflammatory pathways to cervical cancer progression and HIV infection and the
      role of HIV in cervical cancer progression. 

PMID- 24278713
TI  - Alu mobile elements: from junk DNA to genomic gems.
AB  - Alus, the short interspersed repeated sequences (SINEs), are retrotransposons
      that litter the human genomes and have long been considered junk DNA. However,
      recent findings that these mobile elements are transcribed, both as distinct RNA
      polymerase III transcripts and as a part of RNA polymerase II transcripts,
      suggest biological functions and refute the notion that Alus are biologically
      unimportant. Indeed, Alu RNAs have been shown to control mRNA processing at
      several levels, to have complex regulatory functions such as transcriptional
      repression and modulating alternative splicing and to cause a host of human
      genetic diseases. Alu RNAs embedded in Pol II transcripts can promote evolution
      and proteome diversity, which further indicates that these mobile retroelements
      are in fact genomic gems rather than genomic junks. 

PMID- 24278715
TI  - The Association between COMT, BDNF, and NRG1 and Premorbid Social Functioning in
      Patients with Psychosis, Their Relatives, and Controls.
AB  - We investigated the influences of putative candidate genes for psychosis on
      premorbid social adjustment and on premorbid schizoid-schizotypal traits. A
      family-based sample was used including 177 patients with schizophrenia or bipolar
      I disorder with a history of psychotic symptoms, 86 of their unaffected
      relatives, and 116 unrelated healthy controls. Association analyses on the
      combined sample were conducted using the Statistical Analysis for Genetic
      Epidemiology software (SAGE) and adjusting for age, sex, clinical group, and the
      family-based nature of the data. The COMT Val(158)Met and BDNF Val(66)Met
      polymorphisms showed no evidence of association with either phenotype. The SNP
      rs221533 of the NRG1 gene was significantly associated with premorbid adjustment
      in adolescence with TT homozygous subjects having a poorer performance than C
      allele carriers. In the context of neurodevelopmental disorders such as
      schizophrenia and other psychoses, this finding is plausible; however, it is
      preliminary and requires replication in an independent sample. In a broader
      sense, the use of intermediate quantitative phenotypes such as the ones presented
      in this study may be of help to understand the mechanism of action of genetic
      risk factors. 

PMID- 24278717
TI  - Infertility in men with spinal cord injury: research and treatment.
AB  - Spinal cord injury (SCI) occurs most often to young men. Following SCI, most men
      are infertile due to a combination of erectile dysfunction, ejaculatory
      dysfunction and semen abnormalities. Erectile dysfunction may be treated by the
      same therapies that are used in the general population. Similarly, the same
      treatments that are effective to assist conception in couples with non-SCI male
      factor patients are effective in assisting conception in SCI male-factor
      patients. The most apparent differences in male-factor symptoms between SCI and
      non-SCI patients are the high occurrences of anejaculation and atypical semen
      profiles in men with SCI. Methods available to assist ejaculation in men with SCI
      include penile vibratory stimulation and EEJ. Use of surgical sperm retrieval as
      the first line of treatment for anejaculation in men with SCI is controversial.
      Most men with SCI have a unique semen profile characterized by normal sperm
      concentration, but abnormally low sperm motility. Toxic substances in the semen
      contribute to this problem. Despite impaired sperm parameters, pregnancy outcomes
      using sperm from men with SCI are similar to pregnancy outcomes using sperm from
      non-SCI men. Future studies should focus on improving natural ejaculation and
      improving semen quality in these men. 

PMID- 24278718
TI  - Histopathology of pseudoxanthoma elasticum and related disorders: histological
      hallmarks and diagnostic clues.
AB  - Among ectopic mineralization disorders, pseudoxanthoma elasticum (PXE)-a rare
      genodermatosis associated with ocular and cardiovascular manifestations-is
      considered a paradigm disease. The symptoms of PXE are the result of
      mineralization and fragmentation of elastic fibers, the exact pathophysiology of
      which is incompletely understood. Though molecular analysis of the causal gene,
      ABCC6, has a high mutation uptake, a skin biopsy has until now been considered
      the golden standard to confirm the clinical diagnosis. Although the histological
      hallmarks of PXE are rather specific, several other diseases-particularly those
      affecting the skin-can present with clinical and/or histological characteristics
      identical to or highly resemblant of PXE. In this paper, we will summarize the
      histopathological features of PXE together with those of disorders that are most
      frequently considered in the differential diagnosis of PXE. 

PMID- 24278716
TI  - The perception and endogenous modulation of pain.
AB  - Pain is often perceived an unpleasant experience that includes sensory and
      emotional/motivational responses. Accordingly, pain serves as a powerful teaching
      signal enabling an organism to avoid injury, and is critical to survival.
      However, maladaptive pain, such as neuropathic or idiopathic pain, serves no
      survival function. Genomic studies of individuals with congenital insensitivity
      to pain or paroxysmal pain syndromes considerable increased our understanding of
      the function of peripheral nociceptors, and especially of the roles of voltage
      gated sodium channels and of nerve growth factor (NGF)/TrkA receptors in
      nociceptive transduction and transmission. Brain imaging studies revealed a "pain
      matrix," consisting of cortical and subcortical regions that respond to noxious
      inputs and can positively or negatively modulate pain through activation of
      descending pain modulatory systems. Projections from the periaqueductal grey
      (PAG) and the rostroventromedial medulla (RVM) to the trigeminal and spinal
      dorsal horns can inhibit or promote further nociceptive inputs. The "pain matrix"
      can explain such varied phenomena as stress-induced analgesia, placebo effect and
      the role of expectation on pain perception. Disruptions in these systems may
      account for the existence idiopathic pan states such as fibromyalgia. Increased
      understanding of pain modulatory systems will lead to development of more
      effective therapeutics for chronic pain. 

PMID- 24278720
TI  - Biological Processes that Prepare Mammalian Spermatozoa to Interact with an Egg
      and Fertilize It.
AB  - In the mouse and other mammals studied, including man, ejaculated spermatozoa
      cannot immediately fertilize an egg. They require a certain period of residence
      in the female genital tract to become functionally competent cells. As
      spermatozoa traverse through the female genital tract, they undergo multiple
      biochemical and physiological changes collectively referred to as capacitation.
      Only capacitated spermatozoa interact with the extracellular egg coat, the zona
      pellucida. The tight irreversible binding of the opposite gametes triggers a
      Ca(2+)-dependent signal transduction cascade. The net result is the fusion of the
      sperm plasma membrane and the underlying outer acrosomal membrane at multiple
      sites that causes the release of acrosomal contents at the site of sperm-egg
      adhesion. The hydrolytic action of the acrosomal enzymes released, along with the
      hyperactivated beat pattern of the bound spermatozoon, is important factor that
      directs the sperm to penetrate the egg coat and fertilize the egg. The sperm
      capacitation and the induction of the acrosomal reaction are Ca(2+)-dependent
      signaling events that have been of wide interest to reproductive biologists for
      over half a century. In this paper, we intend to discuss data from this and other
      laboratories that highlight the biological processes which prepare spermatozoa to
      interact with an egg and fertilize it. 

PMID- 24278719
TI  - The Role of Sulfhydryl Reactivity of Small Molecules for the Activation of the
      KEAP1/NRF2 Pathway and the Heat Shock Response.
AB  - The KEAP1/NRF2 pathway and the heat shock response are two essential
      cytoprotective mechanisms that allow adaptation and survival under conditions of
      oxidative, electrophilic, and thermal stress by regulating the expression of
      elaborate networks of genes with versatile protective functions. The two pathways
      are independently regulated by the transcription factor nuclear factor-erythroid
      2 p45-related factor 2 (NRF2) and heat shock factor 1 (HSF1), respectively. The
      activity of these transcriptional master regulators increases during conditions
      of stress and also upon encounter of small molecules (inducers), both naturally
      occurring as well as synthetically produced. Inducers have a common chemical
      property: the ability to react with sulfhydryl groups. The protein targets of
      such sulfhydryl-reactive compounds are equipped with highly reactive cysteine
      residues, which serve as sensors for inducers. The initial cysteine-sensed signal
      is further relayed to affect the expression of large networks of genes, which in
      turn can ultimately influence complex cell fate decisions such as life and death.
      The paper summarizes the multiple lines of experimental evidence demonstrating
      that the reactivity with sulfhydryl groups is a major determinant of the
      mechanism of action of small molecule dual activators of the KEAP1/NRF2 pathway
      and the heat shock response. 

PMID- 24278722
TI  - The Impact of Ethnic-Immigrant Status and Obesity-Related Risk Factors on
      Behavioral Problems among US Children and Adolescents.
AB  - We examined the prevalence and correlates of parent-reported behavioral problems
      among immigrants and US-born children aged 6-17 years. The 2007 National Survey
      of Children's Health was used to develop an 11-item factor-based behavioral
      problems index (BPI) and a dichotomous serious behavioral problems (SBP) measure.
      Logistic and least-squares regression and disparity indices were used to analyze
      differentials. BPI scores varied from 92.3 for immigrant Asian children to
      >=102.4 for native Hispanic and Black children. The prevalence of SBP ranged from
      2.9% for immigrant Asian children to 17.0% for native Black children. Children in
      most ethnic-immigrant groups had higher adjusted levels of behavioral problems
      than immigrant Asian children. Native Hispanic children, native and immigrant
      White children, immigrant Black children, and native Asian children had >=3.0
      times higher adjusted odds of SBP than immigrant Asian children. Lower
      socioeconomic status, obesity, physical inactivity, lack of sports participation,
      increased television viewing, and sleep disruption were associated with greater
      behavioral problems. Sociodemographic and behavioral factors accounted for 37.0%
      and 48.5% of ethnic-immigrant disparities in BPI and SBP, respectively. Immigrant
      children had fewer behavioral problems than native-born children. Policies aimed
      at modifying obesity-related behaviors and social environment may lead to
      improved behavioral/emotional health in both immigrant and native children. 

PMID- 24278723
TI  - A Novel ABCA12 Mutation in Two Families with Congenital Ichthyosis.
AB  - Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically
      heterogeneous disorder characterized by hyperkeratosis in addition to dry, scaly
      skin. There are six genes currently known to be associated with the disease.
      Exome sequencing data for two affected individuals with ichthyosis from two
      apparently unrelated consanguineous Pakistani families was analysed. Potential
      candidate mutations were analysed in additional family members to determine if
      the putative mutation segregated with disease status. A novel mutation (c.G4676T,
      p.Gly1559Val) in ABCA12 occurred at a highly conserved residue, segregated with
      disease status in both families, and was not detected in 143 control chromosomes.
      Genotyping with microsatellite markers demonstrated a partial common haplotype in
      the two families, and a common founder mutation could not be excluded. Comparison
      to previously reported cases was consistent with the hypothesis that severe loss
      of function ABCA12 mutations are associated with Harlequin Ichthyosis and
      missense mutations are preferentially associated with milder phenotypes. In
      addition to identifying a possible founder mutation, this paper illustrates how
      advances in genome sequencing technologies could be utilised to rapidly elucidate
      the molecular basis of inherited skin diseases which can be caused by mutations
      in multiple disease genes. 

PMID- 24278724
TI  - How is chimpanzee self-control influenced by social setting?
AB  - Self-control is often required in natural situations involving interactions with
      other individuals, and personal self-control can be compromised if other
      individuals act impulsively. In this study, we tested self-control in pairs of
      chimpanzees in a variety of settings where at least one chimpanzee of each pair
      performed an established test for self-control in which candies accumulated one
      at time as long as the chimpanzee did not eat any of them. When tested alone,
      some chimpanzees exhibited greater self-control as compared to when tested
      alongside a chimpanzee that independently performed the same type of test.
      However, when the nonfocal animal freely consumed rewards while the focal
      chimpanzee performed the accumulation task, the self-control of some focal
      chimpanzees was elevated as compared to when working alone. Finally, when the
      focal and nonfocal animals worked jointly on the same test and the number of
      rewards accumulated was dependent on both animals' continued ability to inhibit
      eating the items, chimpanzees performed the same when housed together or in
      adjacent enclosures. On the whole, the effects of social setting were modest, but
      these results may relate to the literature on vicarious depletion of self
      control, and they present interesting avenues for future research. 

PMID- 24278721
TI  - Stress Response and Pathogenicity of the Necrotrophic Fungal Pathogen Alternaria
      alternata.
AB  - The production of host-selective toxins by the necrotrophic fungus Alternaria
      alternata is essential for the pathogenesis. A. alternata infection in citrus
      leaves induces rapid lipid peroxidation, accumulation of hydrogen peroxide
      (H2O2), and cell death. The mechanisms by which A. alternata avoids killing by
      reactive oxygen species (ROS) after invasion have begun to be elucidated. The
      ability to coordinate of signaling pathways is essential for the detoxification
      of cellular stresses induced by ROS and for pathogenicity in A. alternata. A low
      level of H2O2, produced by the NADPH oxidase (NOX) complex, modulates ROS
      resistance and triggers conidiation partially via regulating the redox-responsive
      regulators (YAP1 and SKN7) and the mitogen-activated protein (MAP) kinase (HOG1)
      mediated pathways, which subsequently regulate the genes required for the
      biosynthesis of siderophore, an iron-chelating compound. Siderophore-mediated
      iron acquisition plays a key role in ROS detoxification because of the
      requirement of iron for the activities of antioxidants (e.g., catalase and SOD).
      Fungal strains impaired for the ROS-detoxifying system severely reduce the
      virulence on susceptible citrus cultivars. This paper summarizes the current
      state of knowledge of signaling pathways associated with cellular responses to
      multidrugs, oxidative and osmotic stress, and fungicides, as well as the
      pathogenicity/virulence in the tangerine pathotype of A. alternata. 

PMID- 24278725
TI  - Childhood asthma: diagnosis and treatment.
AB  - Many children suffer from recurrent coughing, wheezing and chest tightness. In
      preschool children one third of all children have these symptoms before the age
      of six, but only 40% of these wheezing preschoolers will continue to have asthma.
      In older school-aged children the majority of the children have asthma. Quality
      of life is affected by asthma control. Sleep disruption and exercised induced
      airflow limitation have a negative impact on participation in sports and social
      activities, and may influence family life. The goal of asthma therapy is to
      achieve asthma control, but only a limited number of patients are able to reach
      total control. This may be due to an incorrect diagnosis, co-morbidities or poor
      inhalation technique, but in the majority of cases non-adherence is the main
      reason for therapy failures. However, partnership with the parents and the child
      is important in order to set individually chosen goals of therapy and may be of
      help to improve control. Non-pharmacological measures aim at avoiding tobacco
      smoke, and when a child is sensitised, to avoid allergens. In pharmacological
      management international guidelines such as the GINA guideline and the British
      Guideline on the Management of Asthma are leading. 

PMID- 24278726
TI  - The Reporter System for GPCR Assay with the Fission Yeast Schizosaccharomyces
      pombe.
AB  - G protein-coupled receptors (GPCRs) are associated with a great variety of
      biological activities. Yeasts are often utilized as a host for heterologous GPCR
      assay. We engineered the intense reporter plasmids for fission yeast to produce
      green fluorescent protein (GFP) through its endogenous GPCR pathway. As a control
      region of GFP expression on the reporter plasmid, we focused on seven endogenous
      genes specifically activated through the pathway. When upstream regions of these
      genes were used as an inducible promoter in combination with LPI terminator, the
      mam2 upstream region produced GFP most rapidly and intensely despite the high
      background. Subsequently, LPI terminator was replaced with the corresponding
      downstream regions. The SPBC4.01 downstream region enhanced the response with the
      low background. Furthermore, combining SPBC4.01 downstream region with the sxa2
      upstream region, the signal to noise ratio was obviously better than those of
      other regions. We also evaluated the time- and dose-dependent GFP productions of
      the strains transformed with the reporter plasmids. Finally, we exhibited a model
      of simplified GPCR assay with the reporter plasmid by expressing endogenous GPCR
      under the control of the foreign promoter. 

PMID- 24278727
TI  - Diagnosing eosinophilic colitis: histopathological pattern or nosological entity?
AB  - Reports of  "eosinophilic colitis"-raised colonic mucosal eosinophil density in
      patients with lower gastrointestinal symptoms-have increased markedly over the
      last fifteen years, though it remains a rarity. There is no consensus over its
      diagnosis and management, and uncertainty is compounded by the use of the same
      term to describe an idiopathic increase in colonic eosinophils and an
      eosinophilic inflammatory reaction to known aetiological agents such as parasites
      or drugs. In patients with histologically proven colonic eosinophilia, it is
      important to seek out underlying causes and careful clinicopathological
      correlation is advised. Because of the variability of eosinophil density in the
      normal colon, it is recommended that histological reports of colonic eosinophilia
      include a quantitative morphometric assessment of eosinophil density, preferably
      across several sites. Few reported cases of "eosinophilic colitis" meet these
      criteria. As no correlation has been shown between colonic eosinophil density and
      symptoms in older children or adults, it is suggested that treatment should be
      directed towards alleviation of symptoms and response to treatment assessed
      clinically rather than by histological estimates of intramucosal eosinophils. 

PMID- 24278728
TI  - Recent Advances in the Treatment of ST-Segment Elevation Myocardial Infarction.
AB  - ST-segment elevation myocardial infarction (STEMI) represents the most urgent
      condition for patients with coronary artery disease. Prompt diagnosis and
      therapy, mainly with primary angioplasty using stents, are important in improving
      not only acute survival but also long-term prognosis. Recent advances in
      angioplasty devices, including manual aspiration catheters and drug-eluting
      stents, and pharmacologic therapy, such as potent antiplatelet and anticoagulant
      agents, have significantly enhanced the acute outcome for these patients.
      Continuing efforts to educate the public and to decrease the door-to-balloon time
      are essential to further improve the outcome for these high-risk patients. Future
      research to normalize the left ventricular function by autologous stem cell
      therapy may also contribute to the quality of life and longevity of the patients
      surviving STEMI. 

PMID- 24278730
TI  - Uncertainty monitoring by young children in a computerized task.
AB  - Adult humans show sophisticated metacognitive abilities, including the ability to
      monitor uncertainty. Unfortunately, most measures of uncertainty monitoring are
      limited to use with adults due to their general complexity and dependence on
      explicit verbalization. However, recent research with nonhuman animals has
      successfully developed measures of uncertainty monitoring that are simple and do
      not require explicit verbalization. The purpose of this study was to investigate
      metacognition in young children using uncertainty monitoring tests developed for
      nonhumans. Children judged whether stimuli were more pink or blue-stimuli nearest
      the pink-blue midpoint were the most uncertain and the most difficult to
      classify. Children also had an option to acknowledge difficulty and gain the
      necessary information for correct classification. As predicted, children most
      often asked for help on the most difficult stimuli. This result confirms that
      some metacognitive abilities appear early in cognitive development. The tasks of
      animal metacognition research clearly have substantial utility for exploring the
      early developmental roots of human metacognition. 

PMID- 24278732
TI  - The prevalence of polycystic ovary syndrome in women with idiopathic intracranial
      hypertension.
AB  - Purpose. The purpose of this study is to re-evaluate whether the prevalence of
      polycystic ovary syndrome (PCOS) amongst women with idiopathic intracranial
      hypertension (IIH) is higher than in the general population using the NIH
      criteria. Methods. We included all consecutive women with IIH of child-bearing
      age seen at a hospital-based neuro-ophthalmology clinic between the years 2000
      2005. All consenting women included in this study filled-out a screening
      questionnaire aimed at identifying women at risk for PCOS. The endocrinologist
      examined each patient suspect of PCOS as well as their biochemical results and
      diagnosed PCOS according to NIH criteria. The prevalence of PCOS in these women
      with IIH was compared with the reported prevalence of PCOS in the general
      population. Results. Out of 58 women with IIH who completed the study, definite
      PCOS was diagnosed in nine women (9/58; 15.5%). We found a significantly higher
      prevalence of PCOS using the NIH criteria among the IHH study group (15.5%, P =
      0.001) compared to the general population (8.7%). Conclusions. The prevalence of
      PCOS is higher among patients with IHH, compared to the general population. We
      suggest a novel screening questionnaire to aid in the identification of women
      with IIH at risk for PCOS. 

PMID- 24278731
TI  - The neuropathology of autism.
AB  - Autism is a behaviorally defined neurodevelopmental disorder that affects over 1%
      of new births in the United States and about 2% of boys. The etiologies are
      unknown and they are genetically complex. There may be epigenetic effects,
      environmental influences, and other factors that contribute to the mechanisms and
      affected neural pathway(s). The underlying neuropathology of the disorder has
      been evolving in the literature to include specific brain areas in the
      cerebellum, limbic system, and cortex. Part(s) of structures appear to be
      affected most rather than the entire structure, for example, select nuclei of the
      amygdala, the fusiform face area, and so forth. Altered cortical organization
      characterized by more frequent and narrower minicolumns and early overgrowth of
      the frontal portion of the brain, affects connectivity. Abnormalities include
      cytoarchitectonic laminar differences, excess white matter neurons, decreased
      numbers of GABAergic cerebellar Purkinje cells, and other events that can be
      traced developmentally and cause anomalies in circuitry. Problems with
      neurotransmission are evident by recent receptor and binding site studies
      especially in the inhibitory GABA system likely contributing to an imbalance of
      excitatory/inhibitory transmission. As postmortem findings are related to core
      behavior symptoms, and technology improves, researchers are gaining a much better
      perspective of contributing factors to the disorder. 

PMID- 24278733
TI  - Lipoprotein receptors and lipid enzymes in hepatitis C virus entry and early
      steps of infection.
AB  - Viruses are obligate intracellular agents that depend on host cells for
      successful propagation, hijacking cellular machineries to their own profit. The
      molecular interplay between host factors and invading viruses is a continuous
      coevolutionary process that determines viral host range and pathogenesis. The
      hepatitis C virus (HCV) is a strictly human pathogen, causing chronic liver
      injuries accompanied by lipid disorders. Upon infection, in addition to protein
      protein and protein-RNA interactions usual for such a positive-strand RNA virus,
      HCV relies on protein-lipid interactions at multiple steps of its life cycle to
      establish persistent infection, making use of hepatic lipid pathways. This paper
      focuses on lipoproteins in HCV entry and on receptors and enzymes involved in
      lipid metabolism that HCV exploits to enter hepatocytes. 

PMID- 24278729
TI  - Hemoglobin: a nitric-oxide dioxygenase.
AB  - Members of the hemoglobin superfamily efficiently catalyze nitric-oxide
      dioxygenation, and when paired with native electron donors, function as NO
      dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and
      ancient function than the well-known role in O2 transport-storage. Novel
      hemoglobins possessing a NOD function continue to be discovered in diverse life
      forms. Unique hemoglobin structures evolved, in part, for catalysis with
      different electron donors. The mechanism of NOD catalysis by representative
      single domain hemoglobins and multidomain flavohemoglobin occurs through a
      multistep mechanism involving O2 migration to the heme pocket, O2 binding
      reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate
      release, and heme iron re-reduction. Unraveling the physiological functions of
      multiple NODs with varying expression in organisms and the complexity of NO as
      both a poison and signaling molecule remain grand challenges for the NO field.
      NOD knockout organisms and cells expressing recombinant NODs are helping to
      advance our understanding of NO actions in microbial infection, plant senescence,
      cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD
      inhibitors are being pursued for therapeutic applications as antibiotics and
      antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are
      being developed for agriculture, aquaculture, and industry. 

PMID- 24278735
TI  - Clinical pharmacology in old persons.
AB  - The epidemiological transition, with a rapid increase in the proportion in the
      global population aged over 65 years from 11% in 2010 to 22% in 2050 and 32% in
      2100, represents a challenge for public health. More and more old persons have
      multimorbidities and are treated with a large number of medicines. In advanced
      age, the pharmacokinetics and pharmacodynamics of many drugs are altered. In
      addition, pharmacotherapy may be complicated by difficulties with obtaining drugs
      or adherence and persistence with drug regimens. Safe and effective
      pharmacotherapy remains one of the greatest challenges in geriatric medicine. In
      this paper, the main principles of geriatric pharmacology are presented. 

PMID- 24278734
TI  - Formins: emerging players in the dynamic plant cell cortex.
AB  - Formins (FH2 proteins) are an evolutionarily conserved family of eukaryotic
      proteins, sharing the common FH2 domain. While they have been, until recently,
      understood mainly as actin nucleators, formins are also engaged in various
      additional aspects of cytoskeletal organization and signaling, including, but not
      limited to, the crosstalk between the actin and microtubule networks. A
      surprising diversity of domain organizations has been discovered among the FH2
      proteins, and specific domain setups have been found in plants. Seed plants have
      two clades of formins, one of them (Class I) containing mostly transmembrane
      proteins, while members of the other one (Class II) may be anchored to membranes
      via a putative membrane-binding domain related to the PTEN antioncogene. Thus,
      plant formins present good candidates for possible mediators of coordination of
      the cortical actin and microtubule cytoskeletons, as well as their attachment to
      the plasma membrane, that is, aspects of cell cortex organization likely to be
      important for cell and tissue morphogenesis. Although experimental studies of
      plant formin function are hampered by the large number of formin genes and their
      functional redundancy, recent experimental work has already resulted in some
      remarkable insights into the function of FH2 proteins in plants. 

PMID- 24278736
TI  - Smaller fleas: viruses of microorganisms.
AB  - Life forms can be roughly differentiated into those that are microscopic versus
      those that are not as well as those that are multicellular and those that,
      instead, are unicellular. Cellular organisms seem generally able to host viruses,
      and this propensity carries over to those that are both microscopic and less than
      truly multicellular. These viruses of microorganisms, or VoMs, in fact exist as
      the world's most abundant somewhat autonomous genetic entities and include the
      viruses of domain Bacteria (bacteriophages), the viruses of domain Archaea
      (archaeal viruses), the viruses of protists, the viruses of microscopic fungi
      such as yeasts (mycoviruses), and even the viruses of other viruses (satellite
      viruses). In this paper we provide an introduction to the concept of viruses of
      microorganisms, a.k.a., viruses of microbes. We provide broad discussion
      particularly of VoM diversity. VoM diversity currently spans, in total, at least
      three-dozen virus families. This is roughly ten families per category-bacterial,
      archaeal, fungal, and protist-with some virus families infecting more than one of
      these microorganism major taxa. Such estimations, however, will vary with further
      discovery and taxon assignment and also are dependent upon what forms of life one
      includes among microorganisms. 

PMID- 24278737
TI  - Fibrolamellar carcinoma: 2012 update.
AB  - Fibrolamellar carcinomas are a unique type of primary liver cancer. They occur
      most commonly in children and young adults. Their etiology remains a mystery, as
      they are not associated with chronic liver disease. Fibrolamellar carcinomas are
      not indolent tumors, but have an overall better prognosis than typical
      hepatocellular carcinomas, in part because of the younger age at presentation and
      the lack of cirrhosis. The most important prognostic feature is whether the tumor
      is resectable. Histologically, the tumor is made up of large cells that contain
      abundant mitochondria. The nuclei of the tumor cells have prominent nucleoli. The
      tumor cells induce the formation of extensive intratumoral fibrosis, which often
      grows in parallel, or lamellar bands. The tumor cells clearly show hepatocellular
      features but are also unique in showing both biliary and neuroendocrine
      differentiation. The uniqueness of fibrolamellar carcinoma extends to their
      molecular findings. While the genetic abnormalities that lead to fibrolamellar
      carcinomas are not yet known, studies have shown that they lack mutations in the
      genes most commonly mutated in typical hepatocellular carcinoma (TP53 and
      CTNNB1). In this paper, the clinical, pathological, and basic science literature
      on fibrolamellar carcinoma is comprehensively reviewed. Key areas of needed
      research are also discussed. 

PMID- 24278738
TI  - A neutraceutical by design: the clinical application of curcumin in colonic
      inflammation and cancer.
AB  - Unquestionably, the natural food additive curcumin, derived from the colorful
      spice turmeric used in many Asian cuisines, possesses a diverse array of
      biological activities. These range from its anti-inflammatory, antineoplastic,
      and metabolic modifying properties to surprising roles in disorders ranging from
      Alzheimer's disease to cystic fibrosis. Its effects on growth factor receptors,
      signaling molecules, and transcription factors, together with its epigenetic
      effects are widely considered to be extraordinary. These pleiotropic attributes,
      coupled with its safety even when used orally at well over 10 g/day, are
      unparalleled amongst pharmacological agents. However, there is one drawback;
      apart from the luminal gastrointestinal tract where its pharmacology predicts
      that reasonable drug levels can be attained, its broader use is hampered by its
      poor solubility and hence near undetectable plasma levels. Medicinal chemistry
      and nanotechnology have resulted in the generation of compounds where the
      modified drug or its delivery system has improved matters such that this
      shortcoming has been addressed to some extent, with the surprising finding that
      it remains safe to use. It is predicted that either the parental compound or its
      derivatives may eventually find a place in the therapeutic management protocols
      of several conditions. 

PMID- 24278739
TI  - The insulin-like growth factor system and nutritional assessment.
AB  - Over recent years there has been considerable interest in the role of the insulin
      like growth factor (IGF) system in health and disease. It has long been known to
      be dysregulated in states of under- and overnutrition, serum IGF-I levels falling
      in malnourished patients and responding promptly to nutritional support. More
      recently, other proteins in this system have been observed to be dysregulated in
      both malnutrition and obesity. Currently no biochemical marker is sufficiently
      specific for use in screening for malnutrition, but levels may be valuable in
      providing information on nutritional status and in monitoring of nutritional
      support. All have limitations as nutritional markers in that their serum levels
      are influenced by factors other than nutritional status, most importantly the
      acute phase response (APR). Levels should be interpreted along with clinical
      findings and the results of other investigations such as C-reactive protein
      (CRP). This paper reviews data supporting the use of proteins of the IGF system
      as nutritional markers. 

PMID- 24278740
TI  - The role of tau in neurodegenerative diseases and its potential as a therapeutic
      target.
AB  - The abnormal deposition of proteins in and around neurons is a common
      pathological feature of many neurodegenerative diseases. Among these pathological
      proteins, the microtubule-associated protein tau forms intraneuronal filaments in
      a spectrum of neurological disorders. The discovery that dominant mutations in
      the MAPT gene encoding tau are associated with familial frontotemporal dementia
      strongly supports abnormal tau protein as directly involved in disease
      pathogenesis. This and other evidence suggest that tau is a worthwhile target for
      the prevention or treatment of tau-associated neurodegenerative diseases,
      collectively called tauopathies. However, it is critical to understand the normal
      biological roles of tau, the specific molecular events that induce tau to become
      neurotoxic, the biochemical nature of pathogenic tau, the means by which
      pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on
      known differences between normal and abnormal tau, a number of approaches have
      been taken toward the discovery of potential therapeutics. Key questions still
      remain open, such as the nature of the connection between the amyloid- beta
      protein of Alzheimer's disease and tau pathology. Answers to these questions
      should help better understand the nature of tauopathies and may also reveal new
      therapeutic targets and strategies. 

PMID- 24278741
TI  - The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and
      Function at Multiple Subcellular Locations.
AB  - Inherited mutations in the BRCA1 gene predispose to a higher risk of
      breast/ovarian cancer. The BRCA1 tumor suppressor is a 1863 amino acid protein
      with multiple protein interaction domains that facilitate its roles in regulating
      DNA repair and maintenance, cell cycle progression, transcription, and cell
      survival/apoptosis. BRCA1 was first identified as a nuclear phosphoprotein, but
      has since been shown to contain different transport sequences including nuclear
      export and nuclear localization signals that enable it to shuttle between
      specific sites within the nucleus and cytoplasm, including DNA repair foci,
      centrosomes, and mitochondria. BRCA1 nuclear transport and ubiquitin E3 ligase
      enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner
      BARD1 and further modulated by cancer mutations and diverse signaling pathways.
      This paper will focus on the transport, dynamics, and multiple intracellular
      destinations of BRCA1 with emphasis on how regulation of these events has impact
      on, and determines, a broad range of important cellular functions. 

PMID- 24278742
TI  - Screening for Ischemic Heart Disease with Cardiac CT: Current Recommendations.
AB  - Cardiovascular disease remains the leading cause of mortality in the US and
      worldwide, and no widespread screening for this number one killer has been
      implemented. Traditional risk factor assessment does not fully account for the
      coronary risk and underestimates the prediction of risk even in patients with
      established risk factors for atherosclerosis. Coronary artery calcium (CAC)
      represents calcified atherosclerosis in the coronary arteries. It has been shown
      to be the strongest predictor of adverse future cardiovascular events and
      provides incremental information to the traditional risk factors. CAC
      consistently outperforms traditional risk factors, including models such as
      Framingham risk to predict future CV events. It has been incorporated into both
      the European and American guidelines for risk assessment. CAC is the most robust
      test today to reclassify individuals based on traditional risk factor assessment
      and provides the opportunity to better strategize the treatments for these
      subjects (converting patients from intermediate to high or low risk). CAC
      progression has also been identified as a risk for future cardiovascular events,
      with markedly increased events occurring in those patients exhibiting increases
      in calcifications over time. The exact intervals for rescanning is still being
      evaluated. 

PMID- 24278743
TI  - Serotonergic modulation of conditioned fear.
AB  - Conditioned fear plays a key role in anxiety disorders as well as depression and
      other neuropsychiatric conditions. Understanding how neuromodulators drive the
      associated learning and memory processes, including memory consolidation,
      retrieval/expression, and extinction (recall), is essential in the understanding
      of (individual differences in vulnerability to) these disorders and their
      treatment. The human and rodent studies I review here together reveal, amongst
      others, that acute selective serotonin reuptake inhibitor (SSRI) treatment
      facilitates fear conditioning, reduces contextual fear, and increases cued fear,
      chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors
      inhibit the acquisition and expression of contextual fear, 5-HT2A receptors
      facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C
      receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor
      mediates contextual fear, genetically induced increases in serotonin levels are
      associated with increased fear conditioning, impaired cued fear extinction, or
      impaired extinction recall, and that genetically induced 5-HT depletion increases
      fear conditioning and contextual fear. Several explanations are presented to
      reconcile seemingly paradoxical relationships between serotonin levels and
      conditioned fear. 

PMID- 24278744
TI  - Contribution of alpha - and beta -Adrenergic Mechanisms to the Development of
      Pulmonary Edema.
AB  - Endogenous or exogenous catecholamines can induce pulmonary edema (PE). This may
      occur in human pathologic conditions such as in pheochromocytoma or in neurogenic
      pulmonary edema (NPE) but can also be provoked after experimental administration
      of adrenergic agonists. PE can result from stimulation with different types of
      adrenergic stimulation. With alpha-adrenergic treatment, it develops more
      rapidly, is more severe with abundant protein-rich fluid in the alveolar space,
      and is accompanied by strong generalized inflammation in the lung. Similar
      detrimental effects of alpha-adrenergic stimulation have repeatedly been
      described and are considered to play a pivotal role in NPE or in PE in patients
      with pheochromocytoma. Although beta-adrenergic agonists have often been reported
      to prevent or attenuate PE by enhancing alveolar fluid clearance, PE may also be
      induced by beta-adrenergic treatment as can be observed in tocolysis. In
      experimental models, infusion of beta-adrenergic agonists induces less severe PE
      than alpha-adrenergic stimulation. The present paper addresses the current
      understanding of the possible contribution of alpha- and beta-adrenergic pathways
      to the development of PE. 

PMID- 24278745
TI  - Gender Development in 46,XY DSD: Influences of Chromosomes, Hormones, and
      Interactions with Parents and Healthcare Professionals.
AB  - Variables that impact gender development in humans are difficult to evaluate.
      This difficulty exists because it is not usually possible to tease apart
      biological influences on gender from social variables. People with disorders of
      sex development, or DSD, provide important opportunities to study gender within
      individuals for whom biologic components of sex can be discordant with social
      components of gender. While most studies of gender development in people with
      46,XY DSD have historically emphasized the importance of genes and hormones on
      gender identity and gender role, more recent evidence for a significant role for
      socialization exists and is considered here. For example, the influence of
      parents' perceptions of, and reactions to, DSD are considered. Additionally, the
      impact of treatments for DSD such as receiving gonadal surgeries or genitoplasty
      to reduce genital ambiguity on the psychological development of people with 46,XY
      DSD is presented. Finally, the role of multi-disciplinary care including access
      to peer support for advancing medical, surgical and psychosexual outcomes of
      children and adults with 46,XY DSD, regardless of sex of rearing, is discussed. 

PMID- 24278746
TI  - Leaf spectra and weight of species in canopy, subcanopy, and understory layers in
      a venezuelan andean cloud forest.
AB  - We characterize the leaf spectra of tree species of an Andean cloud forest in
      Venezuela, grouped according to position in canopy, subcanopy and understory. We
      measured leaf reflectance and transmittance spectra in the 400-750 nm range using
      a high-resolution spectrometer. Both signals were subtracted from unity to
      calculate the absorbance signal. Nine spectral variables were calculated for each
      signal, three based on wide-bands and six based on features. We measured leaf
      mass per unit area of all species, and calculated efficiency of absorbance, as
      ratio of absorbance in photosynthetic range over leaf mass. Differences among
      groups were significant for several absorbance and transmittance variables, leaf
      mass, and efficiency of absorbance. The clearest differences are between canopy
      and understory species. There is strong correlation for at least one pair of band
      variables for each signal, and each band variable is strongly correlated with at
      least one feature variable for most signals. High canonical correlations are
      obtained between pairs of the three canonical axes for bands and the first three
      canonical axes for features. Absorbance variables produce species clusters having
      the closest correspondence to the species groups. Linear discriminant analysis
      shows that species groups can be sorted by all signals, particularly absorbance. 

PMID- 24278748
TI  - Empirical and theoretical studies on number comparison: design parameters and
      research questions.
AB  - For well over one-hundred years, several key factors have been well established
      in the study of number comparison, including mental number line, numerical
      distance effect, and effect of sensory representation on number processing. The
      purpose of this article is to put some of these studies together to discuss
      design parameters and research questions addressed in the mental number
      comparison studies. Most of the studies discuss sensory representation and
      abstract number representation as well as degree of their interaction. In order
      to give the different views on a particular research question, the author
      classified studies under the related research questions. For example, Stroop and
      size congruity effect studies are addressed under this title chronologically. It
      was very clear that the design parameters and research question might change the
      interpretation of a task. It may be time to shift attention from the question of
      the interaction degree of sensory representation and abstract representation to a
      larger scope. The larger scope would be to understand the differences and
      similarities between different groups using a universal approach. 

PMID- 24278749
TI  - SKIP Downregulation Increases TGF-beta1-Induced Matrix Metalloproteinase-9
      Production in Transformed Keratinocytes.
AB  - Transforming growth factor-beta (TGF-beta1) is a potent inductor of matrix
      metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting
      protein (SKIP) has been described as a regulator of TGF-beta1 signal
      transduction, but its role in the induction of cell malignance by TGF-beta1 has
      not been fully elucidated so far. In the present study, we analyzed the role of
      SKIP on TGF-beta1-induced MMP-9 production. Mouse transformed keratinocytes (PDV)
      were stably transfected with SKIP antisense construct. We observed that SKIP
      depletion provoked an enhancement in the expression of MMP-9 in response to TGF
      beta1 treatment. The downregulation of SKIP produced an enhancement in TGF-beta1
      activated ERK1,2 MAP kinase as well as increased transactivation of downstream
      Elk1 transcription factor. The increased MMP-9 production in response to TGF
      beta1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP
      9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a
      regulatory protein in TGF-beta1-induced MMP-9 expression acting by controlling
      ERK1,2 signaling in transformed cells. 

PMID- 24278751
TI  - Comparative Analysis of the Full-Length Genome Sequence of a Clinical Isolate of
      Human Parainfluenza Virus 4B.
AB  - We are engaged in airborne transmission and epidemiology studies of respiratory
      pathogens, with particular interest in human parainfluenza virus type 4 (hPIV-4)
      and other lesser studied viruses. In this paper, hPIV-4 was detected in primary
      rhesus monkey kidney (PRMK) cells that had been inoculated with nasopharyngeal
      swab material obtained from a child with a mild upper respiratory tract illness.
      Attempts to isolate the virus in pure culture were hampered by the presence of a
      fast-growing simian spumavirus that was a contaminant of the PRMK cells. Total
      RNA was extracted from the PRMK cell culture, and PCR followed by sequencing of a
      subgenomic section of the fusion protein gene suggested the hPIV-4 was subtype
      4B. At the time of this work, two complete but dissimilar hPIV-4B genomes had
      been deposited by others in GenBank. To gain better insights on hPIV-4B, and to
      test methods that we are developing for viral forensics, the entire genomic
      sequence of our virus was determined from archived RNA. The hPIV-4B genomic
      sequence that we determined conforms to the paramyxovirus "rule of six." Here, we
      compare and contrast the genetic features of the three completely sequenced hPIV
      4B genomes currently present in GenBank. 

PMID- 24278750
TI  - The role of proteins in biosilicification.
AB  - Although the use of silicon dioxide (silica) as a constituent of living organisms
      is mainly restricted to diatoms and sponges, the ways in which this process is
      controlled by nature continue to inspire and fascinate. Both diatoms and sponges
      carry out biosilificiation using an organic matrix but they adopt very different
      strategies. Diatoms use small and heavily modified peptides called silaffins,
      where the most characteristic feature is a modulation of charge by attaching long
      chain polyamines (LCPAs) to lysine groups. Free LCPAs can also cooperate with
      silaffins. Sponges use the enzyme silicatein which is homologous to the cysteine
      protease cathepsin. Both classes of proteins form higher-order structures which
      act both as structural templates and mechanistic catalysts for the
      polycondensation reaction. In both cases, additional proteins are continuously
      being discovered which modulate the process further. This paper concentrates on
      the role of these proteins in the biosilification process as well as in various
      applications, highlighting areas where focus on specific protein properties may
      provide further insight. The field of biosilification is a crossroads of
      different disciplines, where insight into the energetics and mechanisms of
      molecular self-assembly combine with fundamental biology, complex multicomponent
      colloidal systems, and an impressive array of potential technological
      applications. 

PMID- 24278747
TI  - Endoplasmic reticulum stress: its role in disease and novel prospects for
      therapy.
AB  - The endoplasmic reticulum (ER) is a multifunctional organelle required for lipid
      biosynthesis, calcium storage, and protein folding and processing. A number of
      physiological and pathological conditions, as well as a variety of
      pharmacological agents, are able to disturb proper ER function and thereby cause
      ER stress, which severely impairs protein folding and therefore poses the risk of
      proteotoxicity. Specific triggers for ER stress include, for example, particular
      intracellular alterations (e.g., calcium or redox imbalances), certain
      microenvironmental conditions (e.g., hypoglycemia, hypoxia, and acidosis), high
      fat and high-sugar diet, a variety of natural compounds (e.g., thapsigargin,
      tunicamycin, and geldanamycin), and several prescription drugs (e.g.,
      bortezomib/Velcade, celecoxib/Celebrex, and nelfinavir/Viracept). The cell reacts
      to ER stress by initiating a defensive process, called the unfolded protein
      response (UPR), which is comprised of cellular mechanisms aimed at adaptation and
      safeguarding cellular survival or, in cases of excessively severe stress, at
      initiation of apoptosis and elimination of the faulty cell. In recent years, this
      dichotomic stress response system has been linked to several human diseases, and
      efforts are underway to develop approaches to exploit ER stress mechanisms for
      therapy. For example, obesity and type 2 diabetes have been linked to ER stress
      induced failure of insulin-producing pancreatic beta cells, and current research
      efforts are aimed at developing drugs that ameliorate cellular stress and thereby
      protect beta cell function. Other studies seek to pharmacologically aggravate
      chronic ER stress in cancer cells in order to enhance apoptosis and achieve tumor
      cell death. In the following, these principles will be presented and discussed. 

PMID- 24278752
TI  - The past, present, and future of public health surveillance.
AB  - This paper provides a review of the past, present, and future of public health
      surveillance-the ongoing systematic collection, analysis, interpretation, and
      dissemination of health data for the planning, implementation, and evaluation of
      public health action. Public health surveillance dates back to the first recorded
      epidemic in 3180 B.C. in Egypt. Hippocrates (460 B.C.-370 B.C.) coined the terms
      endemic and epidemic, John Graunt (1620-1674) introduced systematic data
      analysis, Samuel Pepys (1633-1703) started epidemic field investigation, William
      Farr (1807-1883) founded the modern concept of surveillance, John Snow (1813
      1858) linked data to intervention, and Alexander Langmuir (1910-1993) gave the
      first comprehensive definition of surveillance. Current theories, principles, and
      practice of public health surveillance are summarized. A number of surveillance
      dichotomies, such as epidemiologic surveillance versus public health
      surveillance, are described. Some future scenarios are presented, while current
      activities that can affect the future are summarized: exploring new frontiers;
      enhancing computer technology; improving epidemic investigations; improving data
      collection, analysis, dissemination, and use; building on lessons from the past;
      building capacity; enhancing global surveillance. It is concluded that learning
      from the past, reflecting on the present, and planning for the future can further
      enhance public health surveillance. 

PMID- 24278754
TI  - The evolution of the appendectomy: from open to laparoscopic to single incision.
AB  - Beginning with its initial description by Fitz in the 19th century, acute
      appendicitis has been a significant long-standing medical challenge; today it
      remains the most common gastrointestinal emergency in adults. Already in 1894,
      McBurney advocated for the surgical removal of the inflamed appendix and is
      credited with the initial description of an Open Appendectomy (OA). With the
      introduction of minimally invasive surgery, this classic approach evolved into a
      procedure with multiple, smaller incisions; a technique termed Laparoscopic
      Appendectomy (LA). There is much literature describing the advantages of this
      newer approach. To name a few, patients have significantly less wound infections,
      reduced pain, and a reduction in ileus compared with the OA. In the past few
      years, Single Incision Laparoscopic Appendectomy (SILA) has gained popularity as
      the next major evolutionary advancement in the removal of the appendix. Described
      as a pioneer in the era of "scarless surgery," it involves only one
      transumbilical incision. Patients are postulated to have reduced post-operative
      complications such as infection, hernias, and hematomas, as well as a quicker
      recovery time and less post-operative pain scores, in comparison to its
      predecessors. In this review, we explore the advancement of the appendectomy from
      open to laparoscopic to single incision. 

PMID- 24278753
TI  - Intraductal papillary mucinous neoplasm of the pancreas: an update.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas.
      The etiology is unknown, but increasing evidence suggests the involvement of
      several tumorigenesis pathways, including an association with hereditary
      syndromes. IPMN occurs more commonly in men, with the mean age at diagnosis
      between 64 and 67 years old. At the time of diagnosis, it may be benign, with or
      without dysplasia, or frankly malignant with an invasive carcinoma. Tumors
      arising from the main pancreatic duct are termed main-duct IPMNs, those involving
      the branch ducts, branch-duct IPMNs. In general, small branch-duct IPMNs are
      benign, particularly in asymptomatic patients, and can be safely followed. In
      contrast, main-duct tumors should be surgically resected and examined carefully
      for an invasive component. In the absence of invasion, patient's survival is
      excellent, from 94 to 100%. For patients with an IPMN-associated invasive
      carcinoma, the prognosis overall is better than those with a de novo pancreatic
      ductal adenocarcinoma, with a 5-year survival of 40% to 60% in some series.
      However, no survival advantage can be demonstrated if the invasive component in
      an IPMN patient is that of the conventional tubular type (versus mucinous
      carcinoma). Several histomorphologic variants are recognized, although the
      clinical significance of this "subtyping" is not well defined. 

PMID- 24278755
TI  - Position weight matrix, gibbs sampler, and the associated significance tests in
      motif characterization and prediction.
AB  - Position weight matrix (PWM) is not only one of the most widely used
      bioinformatic methods, but also a key component in more advanced computational
      algorithms (e.g., Gibbs sampler) for characterizing and discovering motifs in
      nucleotide or amino acid sequences. However, few generally applicable statistical
      tests are available for evaluating the significance of site patterns, PWM, and
      PWM scores (PWMS) of putative motifs. Statistical significance tests of the PWM
      output, that is, site-specific frequencies, PWM itself, and PWMS, are in
      disparate sources and have never been collected in a single paper, with the
      consequence that many implementations of PWM do not include any significance
      test. Here I review PWM-based methods used in motif characterization and
      prediction (including a detailed illustration of the Gibbs sampler for de novo
      motif discovery), present statistical and probabilistic rationales behind
      statistical significance tests relevant to PWM, and illustrate their application
      with real data. The multiple comparison problem associated with the test of site
      specific frequencies is best handled by false discovery rate methods. The test of
      PWM, due to the use of pseudocounts, is best done by resampling methods. The test
      of individual PWMS for each sequence segment should be based on the extreme value
      distribution. 

PMID- 24278756
TI  - Noncoding RNAs in Acute Myeloid Leukemia: From Key Regulators to Clinical
      Players.
AB  - Recent analyses have shown that human cells transcribe almost their entire
      genomes, implying the existence of a huge mass of ncRNAs. At the present,
      microRNAs are the most investigated regulative non-coding RNAs. Several studies
      have demonstrated that microRNAs play a crucial role in hematopoietic
      differentiation and hematological malignancies, including acute myeloid leukemia
      (AML). Aberrant expression of microRNAs has been associated with specific genetic
      abnormalities and clinical outcome of patients with AML. In addition, since
      microRNAs can function as either oncogenes or tumor suppressor genes, the
      potential of using these molecules as therapeutic targets opens up new
      opportunities in the future of AML therapy. The recent demonstration that other
      regulatory ncRNAs, in addition to microRNAs, are involved in hematopoietic cell
      differentiation and diseases, suggests that they may also have a biological
      relevance in AML. This paper will describe the role of ncRNAs in AML and discuss
      the expectations for the use of ncRNAs in diagnosis, prognosis, and therapy of
      AML. 

PMID- 24278759
TI  - MammaPrint Feasibility in a Large Tertiary Urban Medical Center: An Initial
      Experience.
AB  - Background. The MammaPrint (MP) diagnostic assay stratifies breast cancer
      patients into high- and low-risk groups using mRNA analysis of a 70-gene profile.
      The assay is validated for assessment of patients with estrogen receptor positive
      or negative tumors less than 5 cm with 3 or fewer malignant lymph nodes.
      TargetPrint (TP) is an assay for assessing estrogen, progesterone, and HER2-neu
      receptor status based on mRNA expression. A potential limitation of these assays
      is that they require an evaluation of fresh tissue samples. There is limited
      published experience describing MP or TP implementation. Methods. Over 10 months,
      4 breast surgeons obtained samples from 54 patients for MP/TP analysis. The
      samples were analyzed by Agendia Labs. The tumors were independently evaluated
      for receptor status using immunohistochemistry (IHC). Retrospectively, we
      identified patients who were assessed by MP/TP during this period. Patients who
      underwent OncotypeDx evaluation were also identified. Results. Of the 54 patients
      receiving MP, 4 were found ineligible for MP risk assessment because >3 lymph
      nodes were found to be malignant. Out of all eligible patients, 14/50 (28%) had
      samples whose quantity of tumor was not sufficient for analysis (QNS). Out of
      eligible patients with tumors <1 cm, 7/8 (88%) had QNS samples. 7/42 with tumors
      >=1 cm (17%) had QNS samples. Nine patients had discordant receptor results when
      evaluated by IHC versus. TP. Of patients who also underwent OncotypeDx testing,
      6/14 (43%) had discordant results with MP. Conclusions. This study indicates that
      using MP/TP assay is feasible in a tertiary care center but there may be utility
      in limiting MP testing to patients with tumors between 1 and 5 cm due to high
      likelihood of uninformative results in subcentimeter tumors. Further study is
      needed to explore the discordance between oncotype and MP results. 

PMID- 24278757
TI  - Proprotein convertase subtilisin/kexin type 9: from the discovery to the
      development of new therapies for cardiovascular diseases.
AB  - The identification of the HMG-CoA reductase inhibitors, statins, has represented
      a dramatic innovation of the pharmacological modulation of hypercholesterolemia
      and associated cardiovascular diseases. However, not all patients receiving
      statins achieve guideline-recommended low density lipoprotein (LDL) cholesterol
      goals, particularly those at high risk. There remains, therefore, an unmet
      medical need to develop additional well-tolerated and effective agents to lower
      LDL cholesterol levels. The discovery of proprotein convertase subtilisin/kexin
      type 9 (PCSK9), a secretory protein that posttranscriptionally regulates levels
      of low density lipoprotein receptor (LDLR) by inducing its degradation, has
      opened a new era of pharmacological modulation of cholesterol homeostasis. This
      paper summarizes the current knowledge of the basic molecular mechanism
      underlying the regulatory effect of LDLR expression by PCSK9 obtained from in
      vitro cell-cultured studies and the analysis of the crystal structure of PCSK9.
      It also describes the epidemiological and experimental evidences of the
      regulatory effect of PCSK9 on LDL cholesterol levels and cardiovascular diseases
      and summarizes the different pharmacological approaches under development for
      inhibiting PCSK9 expression, processing, and the interaction with LDLR. 

PMID- 24278758
TI  - An elegant biosensor molecular beacon probe: challenges and recent solutions.
AB  - Molecular beacon (MB) probes are fluorophore- and quencher-labeled short
      synthetic DNAs folded in a stem-loop shape. Since the first report by Tyagi and
      Kramer, it has become a widely accepted tool for nucleic acid analysis and
      triggered a cascade of related developments in the field of molecular sensing.
      The unprecedented success of MB probes stems from their ability to detect
      specific DNA or RNA sequences immediately after hybridization with no need to
      wash out the unbound probe (instantaneous format). Importantly, the hairpin
      structure of the probe is responsible for both the low fluorescent background and
      improved selectivity. Furthermore, the signal is generated in a reversible
      manner; thus, if the analyte is removed, the signal is reduced to the background.
      This paper highlights the advantages of MB probes and discusses the approaches
      that address the challenges in MB probe design. Variations of MB-based assays
      tackle the problem of stem invasion, improve SNP genotyping and signal-to-noise
      ratio, as well as address the challenges of detecting folded RNA and DNA. 

PMID- 24278761
TI  - Body-surface-area related renal volume: a common normal range from birth to
      adulthood.
AB  - Renal volume is an important parameter of renal development. Deviations from
      normal volume may indicate pathologic conditions. Thus, during childhood, the
      ever changing renal volumes require the continuous referral to normal volume
      charts in order to classify actual volumes, which is rather inconvenient. In
      daily practice this is frequently disregarded and kidneys are evaluated by their
      appearance only. Therefore, we tested the hypothesis that body surface area (BSA)
      and renal volume grow proportionally from birth to adulthood. We divided the
      renal volume of a child by its BSA to get the BSA-related renal volume (BSARV)
      and found no differences between left and right kidneys and a normal distribution
      for all kidneys regardless of the patient's age. BSARV has a common normal range
      for all age groups with the 10th percentile of 45 and the 90th percentile of 85
      mL/m(2). 80% of all kidneys do not exceed the volume of their counterparts by
      more than 20%. BSARV alleviates the correct evaluation of a child's renal volume
      regardless of age and reveals pathological influences by the simple observation
      that a kidney deviates from a former percentile or z-value. This is especially
      valuable in the followup of kidneys with chronic diseases. 

PMID- 24278760
TI  - Quantitative cardiac positron emission tomography: the time is coming!
AB  - In the last 20 years, the use of positron emission tomography (PET) has grown
      dramatically because of its oncological applications, and PET facilities are now
      easily accessible. At the same time, various groups have explored the specific
      advantages of PET in heart disease and demonstrated the major diagnostic and
      prognostic role of quantitation in cardiac PET. Nowadays, different approaches
      for the measurement of myocardial blood flow (MBF) have been developed and
      implemented in user-friendly programs. There is large evidence that MBF at rest
      and under stress together with the calculation of coronary flow reserve are able
      to improve the detection and prognostication of coronary artery disease.
      Moreover, quantitative PET makes possible to assess the presence of microvascular
      dysfunction, which is involved in various cardiac diseases, including the early
      stages of coronary atherosclerosis, hypertrophic and dilated cardiomyopathy, and
      hypertensive heart disease. Therefore, it is probably time to consider the
      routine use of quantitative cardiac PET and to work for defining its place in the
      clinical scenario of modern cardiology. 

PMID- 24278762
TI  - Plant growth-promoting bacteria: mechanisms and applications.
AB  - The worldwide increases in both environmental damage and human population
      pressure have the unfortunate consequence that global food production may soon
      become insufficient to feed all of the world's people. It is therefore essential
      that agricultural productivity be significantly increased within the next few
      decades. To this end, agricultural practice is moving toward a more sustainable
      and environmentally friendly approach. This includes both the increasing use of
      transgenic plants and plant growth-promoting bacteria as a part of mainstream
      agricultural practice. Here, a number of the mechanisms utilized by plant growth
      promoting bacteria are discussed and considered. It is envisioned that in the not
      too distant future, plant growth-promoting bacteria (PGPB) will begin to replace
      the use of chemicals in agriculture, horticulture, silviculture, and
      environmental cleanup strategies. While there may not be one simple strategy that
      can effectively promote the growth of all plants under all conditions, some of
      the strategies that are discussed already show great promise. 

PMID- 24278764
TI  - Relabeling the medications we call antidepressants.
AB  - This paper raises the question about whether the data on the medications we call
      antidepressants justify the label of antidepressant. The authors argue that a
      true antidepressant should be clearly superior to placebo, should offer a
      risk/benefit balance that exceeds that of alternative treatments, should not
      increase suicidality, should not increase anxiety and agitation, should not
      interfere with sexual functioning, and should not increase depression chronicity.
      Unfortunately, these medications appear to fall short on all of these dimensions.
      Many of the "side effects" of these medications have larger effect sizes than the
      antidepressant effect size. To call these medications antidepressants may make
      sense from a marketing standpoint but may be misleading from a scientific
      perspective. Consumers deserve a label that more accurately reflects the data on
      the largest effects and helps them understand the range of effects from these
      medications. In other words, it may make just as much sense to call these
      medications antiaphrodisiacs as antidepressants because the negative effects on
      libido and sexual functioning are so common. It can be argued that a misleading
      label may interfere with our commitment to informed consent. Therefore, it may be
      time to stop calling these medications antidepressants. 

PMID- 24278763
TI  - Tissue factor structure and function.
AB  - Tissue factor (TF) is an integral membrane protein that is essential to life. It
      is a component of the factor VIIa-TF complex enzyme and plays a primary role in
      both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed
      to blood and binds plasma factor VIIa, and the resulting complex initiates a
      series of enzymatic reactions leading to clot formation and vascular sealing.
      Many cells, both healthy, and tumor cells, produce detectable amounts of TF,
      especially when they are stimulated by various agents. Despite the relative
      simplicity and small size of TF, there are numerous contradictory reports about
      the synthesis and presentation of TF on blood cells and circulation in normal
      blood either on microparticles or as a soluble protein. Another subject of
      controversy is related to the structure/function of TF. It has been almost
      commonly accepted that cell-surface-associated TF has low (if any) activity, that
      is, is "encrypted" and requires specific conditions/reagents to become active,
      that is, "decrypted." However there is a lack of agreement related to the
      mechanism and processes leading to alterations in TF function. In this paper TF
      structure, presentation, and function, and controversies concerning these
      features are discussed. 

PMID- 24278765
TI  - Public Health Impact of Legal Termination of Pregnancy in the US: 40 Years Later.
AB  - During the 40 years since the US Supreme Court decision in Doe versus Wade and
      Doe versus Bolton, restrictions on termination of pregnancy (TOP) were overturned
      nationwide. The use of TOP was much wider than predicted and a substantial
      fraction of reproductive age women in the U.S. have had one or more TOPs and that
      widespread uptake makes the downstream impact of any possible harms have broad
      public health implications. While short-term harms do not appear to be excessive,
      from a public perspective longer term harm is conceiving, and clearly more study
      of particular relevance concerns the associations of TOP with subsequent preterm
      birth and mental health problems. Clearly more research is needed to quantify the
      magnitude of risk and accurately inform women with the crisis of unintended
      pregnancy considering TOP. The current US data-gathering mechanisms are
      inadequate for this important task. 

PMID- 24278767
TI  - Free-radical polymer science structural cancer model: a review.
AB  - Polymer free-radical lipid alkene chain-growth biological models particularly for
      hypoxic cellular mitochondrial metabolic waste can be used to better understand
      abnormal cancer cell morphology and invasive metastasis. Without oxygen as the
      final electron acceptor for mitochondrial energy synthesis, protons cannot
      combine to form water and instead mitochondria produce free radicals and acid
      during hypoxia. Nonuniform bond-length shrinkage of membranes related to erratic
      free-radical covalent crosslinking can explain cancer-cell pleomorphism with
      epithelial-mesenchymal transition for irregular membrane borders that "ruffle"
      and warp over stiff underlying actin fibers. Further, mitochondrial hypoxic
      conditions produce acid that can cause molecular degradation. Subsequent low pH
      activated enzymes then provide paths for invasive cell movement through tissue
      and eventually blood-born metastasis. Although free-radical crosslinking creates
      irregularly shaped membranes with structural actin-polymerized fiber extensions
      as filopodia and lamellipodia, due to rapid cell division the overall cell
      modulus (approximately stiffness) is lower than normal cells. When combined with
      low pH-activated enzymes and lower modulus cells, smaller cancer stem cells
      subsequently have a large advantage to follow molecular destructive pathways and
      leave the central tumor. In addition, forward structural spike-like lamellipodia
      protrusions can leverage to force lower-modulus cancer cells through narrow
      openings. By squeezing and deforming even smaller to allow for easier movement
      through difficult passageways, cancer cells can travel into adjacent tissues or
      possibly metastasize through the blood to new tissue. 

PMID- 24278766
TI  - The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal
      Interface in Physiological Bone Turnover and Osteoporosis.
AB  - Although it has long been recognized that inflammation, a consequence of immune
      driven processes, significantly impacts bone turnover, the degree of
      centralization of skeletal and immune functions has begun to be dissected only
      recently. It is now recognized that formation of osteoclasts, the bone resorbing
      cells of the body, is centered on the key osteoclastogenic cytokine, receptor
      activator of NF- kappa B ligand (RANKL). Although numerous inflammatory cytokines
      are now recognized to promote osteoclast formation and skeletal degradation, with
      just a few exceptions, RANKL is now considered to be the final downstream
      effector cytokine that drives osteoclastogenesis and regulates osteoclastic bone
      resorption. The biological activity of RANKL is moderated by its physiological
      decoy receptor, osteoprotegerin (OPG). New discoveries concerning the sources and
      regulation of RANKL and OPG in physiological bone turnover as well as under
      pathological (osteoporotic) conditions continue to be made, opening a window to
      the complex regulatory processes that control skeletal integrity and the depth of
      integration of the skeleton within the immune response. This paper will examine
      the interconnection between bone turnover and the immune system and the
      implications thereof for physiological and pathological bone turnover. 

PMID- 24278770
TI  - Current and future therapies for multiple sclerosis.
AB  - With the introduction of interferon- beta 1b in 1993 as the first FDA-approved
      treatment for multiple sclerosis, the era of treatment of this incurable disease
      began, and its natural course was permanently changed. Currently, seven different
      treatments for patients with multiple sclerosis with different mechanisms of
      action and dissimilar side effect profiles exist. These medications include
      interferon- beta 1a intramuscular (Avonex), interferon- beta 1a subcutaneous
      (Rebif), interferon- beta 1b subcutaneous (Betaseron/Extavia), glatiramer acetate
      (Copaxone), natalizumab (Tysabri), fingolimod (Gilenya), teriflunomide (Aubagio),
      and mitoxantrone (Novantrone). In addition, a large number of clinical trials are
      being conducted to assess the safety and efficacy of various experimental agents
      in patients with multiple sclerosis, including alemtuzumab, dimethyl fumarate,
      laquinimod, rituximab, daclizumab, and cladribine. In this paper, the author
      presents a concise and comprehensive review of present and potential treatments
      for this incurable disease. 

PMID- 24278769
TI  - Molecular cochaperones: tumor growth and cancer treatment.
AB  - Molecular chaperones play important roles in all cellular organisms by
      maintaining the proteome in an optimally folded state. They appear to be at a
      premium in cancer cells whose evolution along the malignant pathways requires the
      fostering of cohorts of mutant proteins that are employed to overcome tumor
      suppressive regulation. To function at significant rates in cells, HSPs interact
      with cochaperones, proteins that assist in catalyzing individual steps in
      molecular chaperoning as well as in posttranslational modification and
      intracellular localization. We review current knowledge regarding the roles of
      chaperones such as heat shock protein 90 (Hsp90) and Hsp70 and their cochaperones
      in cancer. Cochaperones are potential targets for cancer therapy in themselves
      and can be used to assess the likely prognosis of individual malignancies. Hsp70
      cochaperones Bag1, Bag3, and Hop play significant roles in the etiology of some
      cancers as do Hsp90 cochaperones Aha1, p23, Cdc37, and FKBP1. Others such as the
      J domain protein family, HspBP1, TTC4, and FKBPL appear to be associated with
      more benign tumor phenotypes. The key importance of cochaperones for many
      pathways of protein folding in cancer suggests high promise for the future
      development of novel pharmaceutical agents. 

PMID- 24278773
TI  - Cardiovascular risk in psoriasis: a population-based analysis with assessment of
      the framingham risk score.
AB  - Objective. To examine the utility of the Framingham risk score (FRS) in
      estimating cardiovascular risk in psoriasis. Methods. We compared the predicted
      10-year risk of cardiovascular events, namely, cardiovascular death, myocardial
      infarction, heart failure, percutaneous transluminal coronary angioplasty, and
      coronary artery bypass grafting using the FRS, to the observed risk of
      cardiovascular events in a population-based cohort of patients with psoriasis.
      Patients with incident or prevalent adult-onset psoriasis aged 30-79 years
      without prior history of cardiovascular disease were included. Results. Among the
      1197 patients with predicted risk scores, the median FRS was 6.0%, while the
      observed 10-year cardiovascular risk was 6.9% (standardized incidence ratio
      (SIR): 1.14; 95% confidence interval (CI): 0.92-1.42). The SIR was not elevated
      for women nor for men. The differences between observed and predicted
      cardiovascular risks in patients <60 years (SIR: 1.01; 95% CI: 0.73-1.41) or >=60
      years (SIR: 1.26; 95% CI: 0.95-1.68) were not statistically significant.
      Conclusion. There was no apparent difference between observed and predicted
      cardiovascular risks in patients with psoriasis in our study. FRS reasonably
      estimated cardiovascular risk in both men and women as well as in younger and
      older psoriasis patients, suggesting that FRS can be used in risk stratification
      in psoriasis without further adjustment. 

PMID- 24278771
TI  - Brown adipose tissue growth and development.
AB  - Brown adipose tissue is uniquely able to rapidly produce large amounts of heat
      through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat
      can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1
      is only present in small amounts in the fetus and in precocious mammals, such as
      sheep and humans; it is rapidly activated around the time of birth following the
      substantial rise in endocrine stimulatory factors. Brown adipose tissue is then
      lost and/or replaced with white adipose tissue with age but may still contain
      small depots of beige adipocytes that have the potential to be reactivated. In
      humans brown adipose tissue is retained into adulthood, retains the capacity to
      have a significant role in energy balance, and is currently a primary target
      organ in obesity prevention strategies. Thermogenesis in brown fat humans is
      environmentally regulated and can be stimulated by cold exposure and diet,
      responses that may be further modulated by photoperiod. Increased understanding
      of the primary factors that regulate both the appearance and the disappearance of
      UCP1 in early life may therefore enable sustainable strategies in order to
      prevent excess white adipose tissue deposition through the life cycle. 

PMID- 24278772
TI  - Glial-mediated inflammation underlying parkinsonism.
AB  - The interest in studying neuroimmune interactions is increasing in the scientific
      community, and for many researchers, immunity is becoming a crucial factor in the
      understanding of the physiology of the normal brain as well as the biology
      underlying neurodegenerative diseases. Mounting data over the last two decades
      point toward immune and inflammatory alterations as important mediators of the
      progressive dopaminergic degeneration in Parkinson's disease. The purpose of this
      review is to address, under a historical perspective, as well as in the light of
      recent reports, the glial-mediated inflammatory and immune responses that occur
      in Parkinsonism. In line with this, this review also evaluates and highlights
      available anti-inflammatory drugs and putative targets for Parkinson's disease
      therapy for the near future. 

PMID- 24278768
TI  - HIV-1 Trans Infection of CD4(+) T Cells by Professional Antigen Presenting Cells.
AB  - Since the 1990s we have known of the fascinating ability of a complex set of
      professional antigen presenting cells (APCs; dendritic cells,
      monocytes/macrophages, and B lymphocytes) to mediate HIV-1 trans infection of
      CD4(+) T cells. This results in a burst of virus replication in the T cells that
      is much greater than that resulting from direct, cis infection of either APC or T
      cells, or trans infection between T cells. Such APC-to-T cell trans infection
      first involves a complex set of virus subtype, attachment, entry, and replication
      patterns that have many similarities among APC, as well as distinct differences
      related to virus receptors, intracellular trafficking, and productive and
      nonproductive replication pathways. The end result is that HIV-1 can sequester
      within the APC for several days and be transmitted via membrane extensions
      intracellularly and extracellularly to T cells across the virologic synapse.
      Virus replication requires activated T cells that can develop concurrently with
      the events of virus transmission. Further research is essential to fill the many
      gaps in our understanding of these trans infection processes and their role in
      natural HIV-1 infection. 

PMID- 24278774
TI  - Obstacles in haemocompatibility testing.
AB  - ISO 10993-4 is an international standard describing the methods of testing of
      medical devices for interactions with blood for regulatory purpose. The
      complexity of blood responses to biomaterial surfaces and the variability of
      blood functions in different individuals and species pose difficulties in
      standardisation. Moreover, in vivo or in vitro testing, as well as the clinical
      relevance of certain findings, is still matter of debate. This review deals with
      the major remaining problems, including a brief explanation of surface
      interactions with blood, the current ISO 10993 requirements for testing, and the
      role of in vitro test models. The literature is reviewed on anticoagulation,
      shear rate, blood-air interfaces, incubation time, and the importance of
      evaluation of the surface area after blood contact. Two test categories deserve
      further attention: complement and platelet function, including the effects on
      platelets from adhesion proteins, venipuncture, and animal derived- blood. The
      material properties, hydrophilicity, and roughness, as well as reference
      materials, are discussed. Finally this review calls for completing the acceptance
      criteria in the ISO standard based on a panel of test results. 

PMID- 24278776
TI  - Age- and Gender-Specific Components of the Metabolic Syndrome in 2228 First
      Graders: The PEP Family Heart Study.
AB  - Because first graders are critical for excess weight gain, we assessed components
      of the metabolic syndrome (MetS) using the pediatric definition of the
      International Diabetes Federation (IDF). We compared four MetS components as
      defined by the IDF with age- and gender-specific components in 2228 first graders
      at the age of 6. The growth curves were derived from 22113 children and
      adolescents who participated in the PEP Family Heart Study. The aim was to
      determine in first graders precise values of waist circumference (WC), blood
      pressure (BP), triglycerides (TG), and HDL-Cholesterol (HDL-C) based on growth
      curves that were developed for a large German population of youths and to assess
      the prevalence in terms of both definitions at this critical age. The prevalence
      of high blood pressure for age was 13% compared with only 2% according to IDF.
      Because of this considerable divergence, we propose to define MetS components
      based on national growth curves. 

PMID- 24278777
TI  - Rhinovirus-Induced Exacerbations of Asthma and COPD.
AB  - Over the past two decades, increasing evidence has shown that, in patients with
      chronic airways disease, viral infection is the most common cause of
      exacerbation. This review will examine the evidence for viral-induced
      exacerbations of asthma and chronic obstructive lung disease and the potential
      mechanisms by which viruses cause exacerbations. Attention will be focused on
      rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due
      to rhinovirus, which infects relatively few cells in the airway and does not
      cause the cytotoxicity of other viruses such as influenza or respiratory
      syncytial virus, are particularly poorly understood. While the innate immune
      response likely plays a role in rhinovirus-induced exacerbations, its precise
      role, either adaptive or maladaptive, is debated. Because current treatment
      strategies are only partially effective, further research examining the cellular
      and molecular mechanisms underlying viral-induced exacerbations of chronic
      airways diseases is warranted. 

PMID- 24278775
TI  - LIS1 and DCX: Implications for Brain Development and Human Disease in Relation to
      Microtubules.
AB  - Proper lamination of the cerebral cortex requires the orchestrated motility of
      neurons from their place of birth to their final destination. Improper neuronal
      migration may result in a wide range of diseases, including brain malformations,
      such as lissencephaly, mental retardation, schizophrenia, and autism. Ours and
      other studies have implicated that microtubules and microtubule-associated
      proteins play an important role in the regulation of neuronal polarization and
      neuronal migration. Here, we will review normal processes of brain development
      and neuronal migration, describe neuronal migration diseases, and will focus on
      the microtubule-associated functions of LIS1 and DCX, which participate in the
      regulation of neuronal migration and are involved in the human developmental
      brain disease, lissencephaly. 

PMID- 24278779
TI  - Bullous skin diseases: classical types of autoimmune diseases.
AB  - The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus,
      and bullous pemphigoid, are characterized by the blister formation in the skin
      and/or oral mucosa in combination with circulating and deposited autoantibodies
      reactive with (hemi)desmosomes. Koch's postulates, adapted for autoimmune
      diseases, were applied on these skin diseases. It appears that all adapted Koch's
      postulates are fulfilled, and, therefore, these bullous skin diseases are to be
      considered classical autoimmune diseases within the wide and expanding spectrum
      of autoimmune diseases. 

PMID- 24278778
TI  - Nature and nurture of human pain.
AB  - Humans are very different when it comes to pain. Some get painful piercings and
      tattoos; others can not stand even a flu shot. Interindividual variability is one
      of the main characteristics of human pain on every level including the processing
      of nociceptive impulses at the periphery, modification of pain signal in the
      central nervous system, perception of pain, and response to analgesic strategies.
      As for many other complex behaviors, the sources of this variability come from
      both nurture (environment) and nature (genes). Here, I will discuss how these
      factors contribute to human pain separately and via interplay and how epigenetic
      mechanisms add to the complexity of their effects. 

PMID- 24278782
TI  - Modeling to optimize terminal stem cell differentiation.
AB  - Embryonic stem cell (ESC), iPCs, and adult stem cells (ASCs) all are among the
      most promising potential treatments for heart failure, spinal cord injury,
      neurodegenerative diseases, and diabetes. However, considerable uncertainty in
      the production of ESC-derived terminally differentiated cell types has limited
      the efficiency of their development. To address this uncertainty, we and other
      investigators have begun to employ a comprehensive statistical model of ESC
      differentiation for determining the role of intracellular pathways (e.g., STAT3)
      in ESC differentiation and determination of germ layer fate. The approach
      discussed here applies the Baysian statistical model to cell/developmental
      biology combining traditional flow cytometry methodology and specific
      morphological observations with advanced statistical and probabilistic modeling
      and experimental design. The final result of this study is a unique tool and
      model that enhances the understanding of how and when specific cell fates are
      determined during differentiation. This model provides a guideline for increasing
      the production efficiency of therapeutically viable ESCs/iPSCs/ASC derived
      neurons or any other cell type and will eventually lead to advances in stem cell
      therapy. 

PMID- 24278780
TI  - Laboratory diagnosis of invasive aspergillosis: from diagnosis to prediction of
      outcome.
AB  - Invasive aspergillosis (IA), an infection caused by fungi in the genus
      Aspergillus, is seen in patients with immunological deficits, particularly acute
      leukaemia and stem cell transplantation, and has been associated with high rates
      of mortality in previous years. Diagnosing IA has long been problematic owing to
      the inability to culture the main causal agent A. fumigatus from blood.
      Microscopic examination and culture of respiratory tract specimens have lacked
      sensitivity, and biopsy tissue for histopathological examination is rarely
      obtainable. Thus, for many years there has been a great interest in nonculture
      based techniques such as the detection of galactomannan, beta -D-glucan, and DNA
      by PCR-based methods. Recent meta-analyses suggest that these approaches have
      broadly similar performance parameters in terms of sensitivity and specificity to
      diagnose IA. Improvements have been made in our understanding of the limitations
      of antigen assays and the standardisation of PCR-based DNA detection. Thus, in
      more recent years, the debate has focussed on how these assays can be
      incorporated into diagnostic strategies to maximise improvements in outcome
      whilst limiting unnecessary use of antifungal therapy. Furthermore, there is a
      current interest in applying these tests to monitor the effectiveness of therapy
      after diagnosis and predict clinical outcomes. The search for improved markers
      for the early and sensitive diagnosis of IA continues to be a challenge. 

PMID- 24278781
TI  - Psychrophilic enzymes: from folding to function and biotechnology.
AB  - Psychrophiles thriving permanently at near-zero temperatures synthesize cold
      active enzymes to sustain their cell cycle. Genome sequences, proteomic, and
      transcriptomic studies suggest various adaptive features to maintain adequate
      translation and proper protein folding under cold conditions. Most psychrophilic
      enzymes optimize a high activity at low temperature at the expense of substrate
      affinity, therefore reducing the free energy barrier of the transition state.
      Furthermore, a weak temperature dependence of activity ensures moderate reduction
      of the catalytic activity in the cold. In these naturally evolved enzymes, the
      optimization to low temperature activity is reached via destabilization of the
      structures bearing the active site or by destabilization of the whole molecule.
      This involves a reduction in the number and strength of all types of weak
      interactions or the disappearance of stability factors, resulting in improved
      dynamics of active site residues in the cold. These enzymes are already used in
      many biotechnological applications requiring high activity at mild temperatures
      or fast heat-inactivation rate. Several open questions in the field are also
      highlighted. 

PMID- 24278784
TI  - Global Molecular Epidemiology of Cryptococcus neoformans and Cryptococcus gattii:
      An Atlas of the Molecular Types.
AB  - Cryptococcosis is a fungal disease affecting more than one million people per
      year worldwide. The main etiological agents of cryptococcosis are the two sibling
      species Cryptococcus neoformans and Cryptococcus gattii that present numerous
      differences in geographical distribution, ecological niches, epidemiology,
      pathobiology, clinical presentation and molecular characters. Genotyping of the
      two Cryptococcus species at subspecies level supplies relevant information to
      understand how this fungus has spread worldwide, the nature of its population
      structure, and how it evolved to be a deadly pathogen. At present, nine major
      molecular types have been recognized: VNI, VNII, VNB, VNIII, and VNIV among C.
      neoformans isolates, and VGI, VGII, VGIII, and VGIV among C. gattii isolates. In
      this paper all the information available in the literature concerning the
      isolation of the two Cryptococcus species has been collected and analyzed on the
      basis of their geographical origin, source of isolation, level of identification,
      species, and molecular type. A detailed analysis of the geographical distribution
      of the major molecular types in each continent has been described and represented
      on thematic maps. This study represents a useful tool to start new
      epidemiological surveys on the basis of the present knowledge. 

PMID- 24278785
TI  - Biogenesis and Biological Activity of Secondary siRNAs in Plants.
AB  - Two important hallmarks of RNA silencing in plants are (1) its ability to self
      amplify by using a mechanism called transitivity and (2) its ability to spread
      locally and systemically through the entire plant. Crucial advances have been
      made in recent years in understanding the molecular mechanisms of these
      phenomena. We review here these recent findings, and we highlight the recently
      identified endogenous small RNAs that use these advantageous properties to act
      either as patterning signals in important developmental programs or as a part of
      regulatory cascades. 

PMID- 24278783
TI  - Protein-mediated interactions of pancreatic islet cells.
AB  - The islets of Langerhans collectively form the endocrine pancreas, the organ that
      is soley responsible for insulin secretion in mammals, and which plays a
      prominent role in the control of circulating glucose and metabolism. Normal
      function of these islets implies the coordination of different types of endocrine
      cells, noticeably of the beta cells which produce insulin. Given that an
      appropriate secretion of this hormone is vital to the organism, a number of
      mechanisms have been selected during evolution, which now converge to coordinate
      beta cell functions. Among these, several mechanisms depend on different families
      of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin,
      and claudins) and paracrine communications (pannexins) between beta cells, and
      between these cells and the other islet cell types. Also, other proteins
      (integrins) provide communication of the different islet cell types with the
      materials that form the islet basal laminae and extracellular matrix. Here, we
      review what is known about these proteins and their signaling in pancreatic beta 
      cells, with particular emphasis on the signaling provided by Cx36, given that
      this is the integral membrane protein involved in cell-to-cell communication,
      which has so far been mostly investigated for effects on beta cell functions. 

PMID- 24278786
TI  - L-ascorbic Acid: a multifunctional molecule supporting plant growth and
      development.
AB  - L-Ascorbic acid (vitamin C) is as essential to plants as it is to animals.
      Ascorbic acid functions as a major redox buffer and as a cofactor for enzymes
      involved in regulating photosynthesis, hormone biosynthesis, and regenerating
      other antioxidants. Ascorbic acid regulates cell division and growth and is
      involved in signal transduction. In contrast to the single pathway responsible
      for ascorbic acid biosynthesis in animals, plants use multiple pathways to
      synthesize ascorbic acid, perhaps reflecting the importance of this molecule to
      plant health. Given the importance of ascorbic acid to human nutrition, several
      technologies have been developed to increase the ascorbic acid content of plants
      through the manipulation of biosynthetic or recycling pathways. This paper
      provides an overview of these approaches as well as the consequences that changes
      in ascorbic acid content have on plant growth and function. Discussed is the
      capacity of plants to tolerate changes in ascorbic acid content. The many
      functions that ascorbic acid serves in plants, however, will require highly
      targeted approaches to improve their nutritional quality without compromising
      their health. 

PMID- 24278787
TI  - Immune-mediated adverse events associated with ipilimumab ctla-4 blockade
      therapy: the underlying mechanisms and clinical management.
AB  - Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been
      shown to extend overall survival (OS) in previously treated and treatment-naive
      patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling
      with ipilimumab prolongs T-cell activation and restores T-cell proliferation,
      thus amplifying T-cell-mediated immunity and the patient's capacity to mount an
      effective antitumor immune response. While this immunostimulation has
      unprecedented OS benefits in the melanoma setting, it can also result in immune
      mediated effects on various organ systems, leading to immune-related adverse
      events (irAEs). Ipilimumab-associated irAEs are common and typically low grade
      and manageable, but can also be serious and life threatening. The skin and
      gastrointestinal tract are most frequently affected, while hepatic, endocrine,
      and neurologic events are less common. With proper management, most irAEs resolve
      within a relatively short time, with a predictable resolution pattern. Prompt and
      appropriate management of these irAEs is essential and treatment guidelines have
      been developed to assist oncologists and their teams. Implementation of these
      irAE management algorithms will help ensure that patients are able to benefit
      from ipilimumab therapy with adequate control of toxicities. 

PMID- 24278788
TI  - Holocarboxylase synthetase 1 physically interacts with histone h3 in Arabidopsis.
AB  - Biotin is a water-soluble vitamin required by all organisms, but only synthesized
      by plants and some bacterial and fungal species. As a cofactor, biotin is
      responsible for carbon dioxide transfer in all biotin-dependent carboxylases,
      including acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and pyruvate
      carboxylase. Adding biotin to carboxylases is catalyzed by the enzyme
      holocarboxylase synthetase (HCS). Biotin is also involved in gene regulation, and
      there is some indication that histones can be biotinylated in humans. Histone
      proteins and most histone modifications are highly conserved among eukaryotes.
      HCS1 is the only functional biotin ligase in Arabidopsis and has a high homology
      with human HCS. Therefore, we hypothesized that HCS1 also biotinylates histone
      proteins in Arabidopsis. A comparison of the catalytic domain of HCS proteins was
      performed among eukaryotes, prokaryotes, and archaea, and this domain is highly
      conserved across the selected organisms. Biotinylated histones could not be
      identified in vivo by using avidin precipitation or two-dimensional gel analysis.
      However, HCS1 physically interacts with Arabidopsis histone H3 in vitro,
      indicating the possibility of the role of this enzyme in the regulation of gene
      expression. 

PMID- 24278789
TI  - Tai Chi Exercise to Improve Non-Motor Symptoms of Parkinson's Disease.
AB  - BACKGROUND: A substantial number of individuals with Parkinson's disease exhibit
      debilitating non-motor symptoms that decrease quality of life. To date, few
      treatment options exist for the non-motor symptomatology related to Parkinson's
      disease. The goal of this pilot investigation was to determine the effects of Tai
      Chi exercise on the non-motor symptomology in Parkinson's disease. METHODS:
      Twenty-one individuals with Parkinson's disease were enrolled in a Tai Chi
      intervention (n=15) or a noncontact control group (n=6). Participants assigned to
      Tai Chi participated in 60-minute Tai Chi sessions three times per week, for 16
      weeks. Pre and post measures included indices of cognitive-executive function
      including visuomotor tracking and attention, selective attention, working memory,
      inhibition, processing speed and task switching. Additionally, all participants
      were evaluated on the Parkinson's disease Questionnaire-39 and Tinetti's Falls
      Efficacy Scale. RESULTS: Results indicated that the Tai Chi training group had
      significantly better scores following the intervention than the control group on
      the Parkinson's disease Questionnaire-39 total score as well as the emotional
      well-being sub score. Trends for improvement were noted for the Tai Chi group on
      Digits Backwards, Tinetti's Falls Efficacy Scale, and the activities of daily
      living and communication sub scores of the Parkinson's disease Questionnaire-39.
      CONCLUSIONS: This research provides initial data that supports future studies to
      definitively establish efficacy of Tai Chi to improve non-motor features of
      Parkinson's disease.

PMID- 24278792
TI  - Global advances in health and medicine.
AB  - Science, technology, and medicine (STM) are not immune to the widespread and
      persistent crises that have defined the 21st century. We, the editors of Global
      Advances in Health and Medicine (GAHMJ), a new scholarly medical journal, believe
      that solutions in healthcare will be ones that accelerate the application of
      global advances in health and medicine, resulting in improved population-health
      management, healthcare delivery, and patient outcomes. The journal is focused on
      solutions in 3 main areas: (1) systems theory and medicine, (2) the global
      convergence of healthcare practices, and (3) evidence from the point of care (eg,
      medical case reports). And GAHMJ is more than a scholarly medical journal; it is
      a communication platform. The journal itself is cross-disciplinary and peer
      reviewed and offers innovative STM content for the worldwide community of
      healthcare professionals who actively participate in the healthcare debate. 

PMID- 24278793
TI  - Why medical case reports?
AB  - Medicine is built up of single cases. Individual patients-single cases-are the
      essence of what medicine deals with. Every patient is important, and every case
      can be a lesson. Clinician, researcher, and epidemiologist Alvan Feinstein said,
      "In caring for patients, clinicians constantly perform experiments. During a
      single week of active practice, a busy clinician conducts more experiments than
      most of his laboratory colleagues do in a year."(1) Medicine stretches between
      the intertwined poles of being developed in the laboratories of the
      pharmaceutical industry and in the clinical practice of the "clinical champions"
      the innovative clinician, therapist, nurse, or midwife. While the laboratory
      testing route (pharmacology, quality assessment, phase I-IV trials) is well
      established, what about the significant clinical observations? How can they be
      presented scientifically? 

PMID- 24278791
TI  - Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptom
      Severity: Stress Management Skills are Related to Lower Illness Burden.
AB  - BACKGROUND: The onset of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
      (ME/CFS) typically involves reductions in activities of daily living and social
      interactions (jointly referred to as "illness burden"). Emotional distress has
      been linked to increased reported symptoms, and stress management skills have
      been related to lower fatigue severity in CFS patients. Symptom severity and
      illness burden are highly correlated. The ability to manage stress may attenuate
      this relationship, allowing individuals to feel less burdened by the illness
      independent of the severity of their symptoms. PURPOSE: This study aimed to
      evaluate if perceived stress management skills affect illness burden via
      emotional distress, independent of ME/CFS symptom severity. METHODS: A total of
      117 adults with ME/CFS completed measures of perceived stress management skills,
      emotional distress, ME/CFS symptom severity and illness burden. RESULTS:
      Regression analyses revealed that greater perceived stress management skills
      related to less social and fatigue-related illness burden, via lower emotional
      distress. This relationship existed independent of the association of symptom
      severity on illness burden, and was stronger among those not currently employed.
      CONCLUSIONS: Ability to manage stress is associated with a lower illness burden
      for individuals with ME/CFS. Future studies should evaluate the efficacy of
      psychosocial interventions in lowering illness burden by targeting stress
      management skills.

PMID- 24278794
TI  - Systems approaches: a global and historical perspective on integrative medicine.
AB  - The globalization of healing systems is a dance of cultural awareness and
      cultural dominance that has arisen throughout history. With the development of
      greater communication and interest in whole-systems approaches to healing, the
      opportunity for the development of a global perspective on healing has emerged
      with new life force. The birth of integrative holistic healing systems in the
      West, such as naturopathic, homeopathic, anthroposophic, integral and functional
      medicine, and others, echoes the ocean of wisdom present in traditional healing
      systems, such as traditional Chinese medicine (TCM) and Ayurveda. In working to
      integrate the lessons from these systems, we see the inextricable link between
      man and the natural world, we work to understand the root cause of disease, we
      focus on the whole person to return balance, and we use empiric observation in
      large populations over time to grasp the interrelationships inherent in the whole
      systems view of illness and wellness. 

PMID- 24278790
TI  - Systems Epidemiology: A New Direction in Nutrition and Metabolic Disease
      Research.
AB  - Systems epidemiology applied to the field of nutrition has potential to provide
      new insight into underlying mechanisms and ways to study the health effects of
      specific foods more comprehensively. Human intervention and population-based
      studies have identified i) common genetic factors associated with several
      nutrition-related traits and ii) dietary factors altering the expression of genes
      and levels of proteins and metabolites related to inflammation, lipid metabolism
      and/or gut microbial metabolism, results of high relevance to metabolic disease.
      System-level tools applied type 2 diabetes and related conditions have revealed
      new pathways that are potentially modified by diet and thus offer additional
      opportunities for nutritional investigations. Moving forward, harnessing the
      resources of existing large prospective studies within which biological samples
      have been archived and diet and lifestyle have been measured repeatedly within
      individual will enable systems-level data to be integrated, the outcome of which
      will be improved personalized optimal nutrition for prevention and treatment of
      disease.

PMID- 24278795
TI  - News from around the world.

PMID- 24278796
TI  - Chinese scalp acupuncture for cerebral palsy in a child diagnosed with stroke in
      utero.
AB  - A 6-year-old patient with cerebral palsy was treated with Chinese scalp
      acupuncture. The Speech I, Speech II, Motor, Foot motor and sensory, and Balance
      areas were stimulated once a week, then every other week for 15 sessions. His
      dysarthria, ataxia, and weakness of legs, arms, and hands showed significant
      improvement from each scalp acupuncture treatment, and after 15 sessions, the
      patient had recovered completely. This case report demonstrates that Chinese
      scalp acupuncture can satisfactorily treat a child with cerebral palsy. More
      research and clinical trials are needed so that the potential of scalp
      acupuncture to treat cerebral palsy can be fully explored and utilized. 

PMID- 24278797
TI  - Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing
      Mistletoe Treatment: Two Case Reports.
AB  - BACKGROUND: Mistletoe is a complementary cancer treatment that is widely used,
      usually in addition to and alongside recommended conventional cancer therapy.
      However, little is known about its use, effectiveness, and safety in the
      treatment of cutaneous lymphoma. CASE REPORT: Two patients with primary cutaneous
      B-cell lymphoma (pT2bcNxM0 follicle center and pT2ac-NxM0 marginal zone) either
      declined or postponed recommended conventional treatment and received high-dose,
      fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous,
      and intravenous application was given; and one patient also underwent whole-body
      hyperthermia. The lymphoma regressed over a period of 12 and 8 months,
      respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g
      mistletoe extract, respectively. The patients are in remission to date, 3.5 years
      after commencement of treatment. Neither patient received conventional cancer
      treatment during the entire observation period.

PMID- 24278798
TI  - Successful Treatment of Chronic Viral Hepatitis With High-dilution Medicine.
AB  - INTRODUCTION: Two cases of viral hepatitis that had failed conventional therapy
      are presented. Both were subsequently treated with protocols using homeopathic
      medicines as detailed below. Both patients sustained remissions for 2 years after
      taking ultradilute natural medicines after their conventional treatment had been
      discontinued. METHODS: The treatment protocol included Chelidonium majus 6X and
      Thuja 30C as the main medicines. Other homeopathic medicines were used as
      detailed below. Cases were confirmed with standard hepatitis antibody and viral
      measurements. Patients were followed for more than 2 years with measurements of
      viral counts, liver enzymes, and other relevant biomarkers of liver disease.
      RESULTS: Both patients are alive and functioning normally in their home
      environments more than 2 years after treatment initiation. DISCUSSION: We review
      the literature related to the chief medicines used in these cases and find that
      they have known and demonstrated therapeutic effects suggesting plausible
      mechanisms of action in these cases. CONCLUSIONS: Clinical trials of this
      homeopathic treatment protocol should be conducted to explore the therapeutic
      potential of these medicines for treatment of viral hepatitis.

PMID- 24278799
TI  - Worst Cases Reported to the NAFKAM International Registry of Exceptional Courses
      of Disease.

PMID- 24278800
TI  - A Patient-defined "Best Case" of Multiple Sclerosis Related to the Use of
      Complementary and Alternative Medicine.
AB  - Chronically ill people are frequent users of complementary and alternative
      medicine (CAM). Some patients experience great benefits from their use of CAM,
      like patient "XX" in this case report. XX was diagnosed with secondary
      progressive multiple sclerosis in 2004 and has reported a "best case" after the
      use of Dr Birgitta Brunes' unconventional treatment. The patient reports that
      many of her symptoms that, according to her neurologist, were irreversible are
      gone or have been greatly reduced. Such patient-defined "best cases" related to
      the use of CAM should be further explored to optimize and safeguard patients'
      treatment decisions and treatment outcomes. 

PMID- 24278801
TI  - Efficacy of an Emotion Self-regulation Program for Promoting Development in
      Preschool Children.
AB  - This work reports the results of an evaluation study to assess the efficacy of
      the Early HeartSmarts (EHS) program in schools of the Salt Lake City, Utah,
      School District. The EHS program is designed to guide teachers with methods that
      support young children (3-6 y old) in learning emotion self-regulation and key
      age-appropriate socioemotional competencies with the goal of facilitating their
      emotional, social, and cognitive development. The study was conducted over one
      school year using a quasiexperimental longitudinal field research design with 3
      measurement points (baseline, preintervention, and postintervention) using The
      Creative Curriculum Assessment (TCCA), a teacher-scored, 50-item instrument
      measuring students growth in 4 areas of development: social/emotional, physical,
      cognitive, and language development. Children in 19 preschool classrooms in the
      Salt Lake City School District were divided into intervention and control group
      samples (n = 66 and n = 309, respectively; mean age = 3.6 y). The intervention
      classes were specifically selected to target children of lower socioeconomic and
      ethnic minority backgrounds. Overall, there is compelling evidence of the
      efficacy of the EHS program in increasing total psychosocial development and each
      of the 4 development areas measured by the TCCA: the results of a series of
      analyses of covariance found a strong, consistent pattern of large, significant
      differences on the development measures favoring preschool children who received
      the EHS program over those in the control group. 

PMID- 24278802
TI  - The NAFKAM International Registry of Exceptional Courses of Disease Related to
      the Use of Complementary and Alternative Medicine.
AB  - The increasing use of complementary and alternative medicine (CAM) represents a
      continuing demand for treatment approaches in parallel with, or as an alternative
      to, conventional healthcare delivery.(1,2) Some patients report considerable
      health improvements related to their use of CAM,(3-6) and others report no effect
      or possibly harm.(7) Limited efforts have been made so far to systematically
      collect patients' personal experiences with various CAM therapies. Methods to
      collect "best cases" after the use of CAM in cancer patients have been initiated
      in the United States and Germany.(5,8,9.) 

PMID- 24278803
TI  - The global coherence initiative: creating a coherent planetary standing wave.
AB  - The much anticipated year of 2012 is now here. Amidst the predictions and cosmic
      alignments that many are aware of, one thing is for sure: it will be an
      interesting and exciting year as the speed of change continues to increase,
      bringing both chaos and great opportunity. One benchmark of these times is a
      shift in many people from a paradigm of competition to one of greater
      cooperation. All across the planet, increasing numbers of people are practicing
      heart-based living, and more groups are forming activities that support positive
      change and creative solutions for manifesting a better world. The Global
      Coherence Initiative (GCI) is a science-based, co-creative project to unite
      people in heart-focused care and intention. GCI is working in concert with other
      initiatives to realize the increased power of collective intention and
      consciousness. The convergence of several independent lines of evidence provides
      strong support for the existence of a global information field that connects all
      living systems and consciousness. Every cell in our bodies is bathed in an
      external and internal environment of fluctuating invisible magnetic forces that
      can affect virtually every cell and circuit in biological systems. Therefore, it
      should not be surprising that numerous physiological rhythms in humans and global
      collective behaviors are not only synchronized with solar and geomagnetic
      activity, but disruptions in these fields can create adverse effects on human
      health and behavior. The most likely mechanism for explaining how solar and
      geomagnetic influences affect human health and behavior are a coupling between
      the human nervous system and resonating geomagnetic frequencies, called Schumann
      resonances, which occur in the earth-ionosphere resonant cavity and Alfven waves.
      It is well established that these resonant frequencies directly overlap with
      those of the human brain and cardiovascular system. If all living systems are
      indeed interconnected and communicate with each other via biological,
      electromagnetic, and nonlocal fields, it stands to reason that humans can work
      together in a co-creative relationship to consciously increase the coherence in
      the global field environment, which in turn distributes this information to all
      living systems within the field. GCI was established to help facilitate the shift
      in global consciousness from instability and discord to balance, cooperation, and
      enduring peace. A primary goal of GCI is to test the hypothesis that large
      numbers of people when in a heart-coherent state and holding a shared intention
      can encode information on the earth's energetic and geomagnetic fields, which act
      as carrier waves of this physiologically patterned and relevant information. In
      order to conduct this research, a global network of 12 to 14 ultrasensitive
      magnetic field detectors specifically designed to measure the earth's magnetic
      resonances is being installed strategically around the planet. More important is
      GCI's primary goal to motivate as many people as possible to work together in a
      more coherent and collaborative manner to increase the collective human
      consciousness. If we are persuaded that not only external fields of solar and
      cosmic origins but also human attention and emotion can directly affect the
      physical world and the mental and emotional states of others (consciousness), it
      broadens our view of what interconnectedness means and how it can be
      intentionally utilized to shape the future of the world we live in. It implies
      that our attitudes, emotions, and intentions matter and that coherent,
      cooperative intent can have positive effects. GCI hypothesizes that when enough
      individuals and social groups increase their coherence baseline and utilize that
      increased coherence to intentionally create a more coherent standing reference
      wave in the global field, it will help increase global consciousness. This can be
      achieved when an increasing number of people move towards more balanced and self
      regulated emotions and responses. This in turn can help facilitate cooperation
      and collaboration in innovative problem solving and intuitive discernment for
      addressing society's significant social, environmental, and economic problems. In
      time, as more individuals stabilize the global field and families, workplaces,
      and communities move to increased social coherence, it will lead to increased
      global coherence. This will be indicated by countries adopting a more coherent
      planetary view so that social and economic oppression, warfare, cultural
      intolerance, crime, and disregard for the environment can be addressed
      meaningfully and successfully. 

PMID- 24278804
TI  - The problem with science-the context and process of care: an excerpt from
      remodelling medicine.
AB  - The goal of science is truth through knowledge. But medicine's truth is not
      altogether the same as science's truth.Science works with ideas, imagination and
      intuition, but essentially has to do with facts. Medicine has also to deal with
      meaning.This is not an argument for less science in medicine, but for more and
      better science; better in the sense of better attuned to 'the rest of
      life'.Truthfulness is a core principle of medical practice and medical
      science.But a kind of untruthfulness is common in day-to-day clinical
      practice.The fundamental untruth is the illusion of certainty.The inexcusable
      untruth is to reduce the patient's problem to it to its narrow biomedical
      parameters and to allow the patient as a person to vanish from our gaze.Science
      fails medicine by the narrowness of the scope of things it is willing to
      investigate. Important areas of medicine have been neglected as a consequence.The
      medical research culture must change if it is to promote science for
      understanding alongside science for manipulation. We need to be unsparingly
      critical of the distinction between useful science and wasteful science."Medical
      knowledge is not knowledge acquired primarily for its own sake (but) for a
      specific purpose-the care of the sick."(1.) 

PMID- 24278805
TI  - Summary of Findings Tables: Presenting the Main Findings of Cochrane
      Complementary and Alternative Medicine-related Reviews in a Transparent and
      Simple Tabular Format.
AB  - The systematic review is widely accepted as the most reliable and objective
      method for evaluating the effects of healthcare interventions, including
      complementary and alternative medicine (CAM) therapies. Systematic reviews use
      explicit, transparent, and well-documented methods to find, evaluate, and
      synthesize the best available research studies related to a specific research
      question. Systematic reviews of healthcare treatment typically have focused on
      randomized controlled trials (RCTs) because RCTs are widely regarded as the study
      design providing the most reliable estimates of a healthcare treatment's effects.
      Systematic reviewers aim to evaluate and appraise relevant RCTs using objective
      and reproducible methods to provide an unbiased assessment of the evidence for a
      given therapy. Systematic reviews sometimes include a meta-analysis, the
      quantitative combining (pooling) of results from similar but separate RCTs to
      obtain an overall effect estimate. 

PMID- 24278807
TI  - Review of clinical applications of scalp acupuncture for paralysis: an excerpt
      from chinese scalp acupuncture.
AB  - Chinese scalp acupuncture is a contemporary acupuncture technique integrating
      traditional Chinese needling methods with Western medical knowledge of
      representative areas of the cerebral cortex. It has been proven to be a most
      effective technique for treating acute and chronic central nervous system
      disorders. Scalp acupuncture often produces remarkable results with just a few
      needles and usually brings about immediate improvement, sometimes taking only
      several seconds to a minute. Acupuncture, a therapeutic technique of Oriental
      Medicine, can be traced back more than 2500 years. Throughout its long history,
      acupuncture has evolved as its own unique traditional medicine. By embracing
      newly developed knowledge and technology, the profession continues to create
      additional methods of treatment. Techniques such as electrical and laser
      acupuncture and even new acupuncture points are currently being developed. We
      believe scalp acupuncture, which integrates Western medicine with Traditional
      Chinese Medicine, to be the most significant development that Chinese acupuncture
      has made in the past 60 years. 

PMID- 24278806
TI  - Fever in Cancer Treatment: Coley's Therapy and Epidemiologic Observations.
AB  - In the fall of 1890, an athletic, self-possessed, and thoughtful 17-year-old
      girl, who had just returned from an adventurous trip to Alaska where she had hurt
      her hand in a trivial accident, went to see a young, innovative surgeon in his
      new practice in New York City. Barely out of Harvard Medical School, he was a
      rising star in New York surgical circles, and the young woman asked him for help
      with her poorly healing, swollen, and naggingly painful injury. This visit had a
      far-reaching effect on cancer research, American philanthropy, and the career of
      the young man, William Coley, MD (1862-1936, Figure 1). The patient, Elisabeth
      Dashiell, confidant and close friend of John D. Rockefeller, Jr, was diagnosed by
      Coley with a highly aggressive round cell sarcoma, and despite radical surgery
      and in spite of Coley's undoubtedly fine surgical skills and intensive care, a
      rapid progression of the cancer, immense suffering, and Elisabeth's death a few
      months later could not be prevented. 

PMID- 24278808
TI  - Cochrane summary of findings: horse chestnut seed extract for chronic venous
      insufficiency.
AB  - As part of its efforts to disseminate the results of Cochrane reviews to a wider
      audience, the Cochrane Complementary and Alternative Medicine (CAM) Field
      develops Summary of Findings (SoF) tables and then uses these tables as a basis
      for its Plain Language Summaries. In each SoF table, the most important outcomes
      of the review, the effect of the intervention on each outcome, and the quality of
      the evidence for each outcome are presented. The process of developing the SoF
      table involves deciding which outcomes to present for which time points and
      evaluating the strength and quality of the evidence for the outcomes. The
      Cochrane CAM Field contacted the authors of this review to request clarification
      on any points that are not understood in the Cochrane review and also to request
      their review of the SoF. In this article, review authors in the Cochrane
      Collaboration reviewed the effects of horse chestnut seed extract for chronic
      venous insufficiency. 

PMID- 24278809
TI  - Globalization of healthcare.
AB  - Globalization-the increasing transnational circulation of money, goods, people,
      ideas, and information worldwide-is generally recognized as one of the most
      powerful forces shaping our current and future history. How is it affecting
      healthcare, and in that context, what is the purpose and significance of Global
      Advances in Health and Medicine (GAHM), publisher of this journal? Our goal is
      not homogenization but rather to provide an opportunity for integration,
      convergence, and collaboration across cultures. By respecting and conserving the
      richness and diversity of each new medicine, we embrace globalization.
      Globalization is of course not new; it began in the Renaissance and particularly
      with the 15th- and 16th-century voyages of exploration by Columbus, Magellan, and
      others. Since the beginning of time, there have been interactions and exchanges
      among different peoples and cultures. However, the current magnitude of
      globalization is unprecedented and yet still expanding rapidly. 

PMID- 24278811
TI  - News from around the world.

PMID- 24278810
TI  - Case reports on cancer therapies: the urgent need to improve the reporting
      quality.
AB  - Current guidelines for certain cancer therapies mainly provide recommendations
      for therapy options treating the primary tumors. However, first-choice treatments
      for advanced or metastasizing tumors are described only rarely if at all. In such
      cases, one or more individual treatment options are chosen by the physician
      depending on the medical need of the patient and considering the acceptance of
      this treatment by the patient. Often, well-known drugs are selected with a
      different dosing than is indicated in the drug information leaflet. In other
      cases, drugs not yet approved for this particular type of cancer are used off
      label or certain therapies are used in combination or consecutively in a manner
      not reported before. With the increasing research on personalized medicine,
      particularly in treating cancer, case reports on innovative drug therapies or
      newly developed surgical interventions may provide extremely valuable information
      in instances where randomized controlled trials may not be feasible (eg, because
      of a low patient number or ethical considerations). 

PMID- 24278812
TI  - Propranolol for infantile hemangiomas.
AB  - Hemangiomas are common vascular birthmarks that usually present a predictable
      pattern of proliferation and ultimate involution. Most do not require any
      treatment. When intervention is clinically indicated, medical and surgical
      options exist. Historically, corticosteroids have been used and have been shown
      to slow or stop the growth of a majority of hemangiomas; however, growth concerns
      and infectious complications have complicated their use. In 2008, a letter to the
      editor in The New England Journal of Medicine described another serendipitous
      observation of the effect of the nonselective beta-blocker, propranolol, on
      hemangiomas in 9 cases. This finding has been expanded by the authors of this
      original observation as well as others. 

PMID- 24278813
TI  - A Homeopathic Arnica Patch for the Relief of Cellulitis-derived Pain and Numbness
      in the Hand.
AB  - OBJECTIVES: Arnica montana, belonging to the Compositae family, is a plant with a
      longstanding tradition of relieving pain and/or inflammation in muscles and
      joints and may thus represent an alternative to nonsteroidal antiinflammatory
      drugs, which are often ineffective or lead to a number of adverse effects. A
      homeopathic arnica patch (3X dilution according to the Homeopathic Pharmacopoeia
      of the United States) was developed to alleviate pain symptoms in the back and
      neck muscles and joints. CASE PRESENTATION: The present case report describes the
      treatment outcome after administration of the arnica patch in a 55-year-old
      female patient with pain in the right hand and numbness in the fourth finger
      after cellulitis in the palmar area. The cellulitis was treated with antibiotics,
      but pain symptoms remained at 7 points on a 0-to-10-point visual analog scale
      (VAS) for pain despite intake of oral ibuprofen and oral and topical application
      of an arnica-containing complex homeopathic ointment. Ten arnica patches were
      dispensed to the patient. She cut the patch into strips to cover all painful
      areas of the hand and applied them at night. After 3 days, she reported a
      substantial decrease in pain symptoms (VAS = 1) and a marked decrease in numbness
      and in the size of a tender nodule on the third metacarpal area. Moreover, the
      patient was able to sleep through the night without being awakened by the pain.
      The symptoms declined further during the next 2 days. CONCLUSION: This case
      demonstrates that after a relatively short period of time, the administration of
      the arnica patch on the hand provided a marked reduction of pain and recovery of
      functionality of the hand.

PMID- 24278814
TI  - Spontaneous normal sinus rhythm conversion using integrative medicine in atrial
      fibrillation.
AB  - The relationship between acute life stress and the development of atrial
      fibrillation (AF) has been noted in the literature. However, the use of
      integrative medicine (IM) in restoring cardiac rhythm has not been adequately
      studied. This case report describes how an IM approach was used in a patient with
      atrial fibrillation and acute pain. Spontaneous cardioversion to normal sinus
      rhythm occurred during the IM session, in addition to marked decreases in self
      reported pain, anxiety, and nausea at the conclusion of IM treatment. These
      results provide initial support that for some cases of AF, IM therapies can help
      to reduce costs via avoidance of additional hospitalization,
      electrocardioversion, and general anesthesia. 

PMID- 24278815
TI  - Hypertension.
AB  - Hypertension is responsible for roughly one-in-six adult deaths annually in the
      United States and is associated with five of the top nine causes of death.(1) Ten
      trillion dollars is the estimated annual cost worldwide of the direct and
      indirect effects of hypertension.(2,3) In the U.S. alone, costs estimated at
      almost $74 billion in 2009 placed a huge economic burden on the health care
      system.(4) The prevalence of hypertension increases with advancing age to the
      point where more than half of people 60 to 69 years of age and at least three
      fourths of those 70 years of age and older are affected.(5) Most individuals with
      hypertension do not have it adequately controlled.(1,6) Medication noncompliance
      due to avoidance of side effects is suggested to be a primary factor.(6) The
      epidemic incidence of hypertension and its significant cost to society indicate
      that a well-tolerated, cost-effective approach to treatment is urgently needed. 

PMID- 24278816
TI  - Statin-induced Myopathy.
AB  - Heart disease (HD) is the number one killer in the United States.(1) In 2006, the
      direct and indirect costs associated with cardiovascular disease in the United
      States were estimated at 400 billion dollars.(2) Statin therapy for cholesterol
      reduction is a mainstay intervention for cardiovascular disease (CVD) as
      reflected in atorvastatin's status as the number one prescribed medication in the
      United States.(3) Statin therapy, however, is also associated with side effects
      that signal mitochondrial distress. A commonly reported statin-induced symptom is
      myalgia, which is defined as muscle pain without an associated elevation of serum
      creatine kinase (CK). In clinical trials, the reports of myalgia vary from less
      than 1% to 25% of patients.(4) Myopathy is a general term defined as an abnormal
      condition or disease of muscle tissue. Myopathy includes myalgia, myositis
      (inflammation of muscle tissue associated with elevated CK) and the very serious
      condition rhabdomyolysis (extreme myositis). Histological findings in statin
      induced myopathy demonstrate electron chain dysfunction making "mitochondrial
      myopathy" the more precise term.(5) Mitochondrial myopathy has been associated
      with statin-induced CoQ10 depletion.(5) Given the density of mitochondria in
      cardiomyocytes, and CoQ10's role in mitochondrial energy production, depletion
      has long been associated with increased risk for heart disease.(6-7) In the case
      below, mitochondrial-specific organic acids, serum CoQ10, vitamin D and clinical
      history all suggest statin-induced mitochondrial myopathy, despite normal serum
      CK. 

PMID- 24278818
TI  - Holistic Care in the US Military I-The Epidaurus Project: An Initiative in
      Holistic Medicine for the Military Health System, 2001-2012.
AB  - This article describes the history and findings of the Epidaurus Project, a
      Uniformed Services University-affiliated project to bring holistic care and
      evidence-based design into the Military Health System (MHS). A distinguished
      group of civilian thought leaders contributed. The 2005 Base Realignment and
      Closure process offered a chance to implement the Epidaurus agenda. A new
      integrated healthcare delivery system, centered around the Walter Reed National
      Military Medical Center at Bethesda, Maryland, was the result. These facilities
      will be templates for a new generation of MHS "healing environments" and a model
      for innovative systems of healthcare nationwide. The Epidaurus Project represents
      a significant collaboration between civilian medicine and the military in times
      of war. 

PMID- 24278817
TI  - The Heart and Medicine: Exploring the Interconnectedness of Cardiometabolic
      related Concerns Through a Systems Biology Approach.
AB  - Patients do not just wake up one morning with cardiac disease. Instead there is
      an extended preclinical phase during which lifestyle choices determine outcome.
      Recent advances in our understanding of oxidative stress, endocrine signaling,
      immune/inflammatory balance, and energy production illuminate opportunities for
      efficacious intervention. A thorough exploration of these pathophysiologies will
      allow physicians the opportunity to offer their patients a journey away from
      illness and disease to optimal wellness. 

PMID- 24278821
TI  - Call for articles.

PMID- 24278820
TI  - The effect of probiotics for preventing acute upper respiratory tract infections.
AB  - As part of its efforts to disseminate the results of Cochrane reviews to a wider
      audience, the Cochrane Complementary and Alternative Medicine (CAM) Field
      develops Summary of Findings (SoF) tables and then uses those tables as a basis
      for its plain-language summaries. Each SoF table presents the most important
      outcomes for the review as well as the effect of the intervention and the quality
      of the evidence for each outcome. The process of developing the SoF table
      involves deciding which outcomes to present for which time points and evaluating
      the strength and quality of the evidence for the outcomes. In this article, we
      present a Cochrane review about the effects of the use of probiotics for
      preventing acute upper respiratory tract infections. We contacted the authors of
      the Cochrane review to request clarification on points that we did not understand
      and to have them review the SoF table. 

PMID- 24278819
TI  - Coherence: a novel nonpharmacological modality for lowering blood pressure in
      hypertensive patients.
AB  - This study examined the efficacy of teaching emotional self-regulation techniques
      supported by heart rhythm coherence training (emWave Personal Stress Reliever) as
      a means to quickly lower blood pressure (BP) in patients diagnosed with
      hypertension. Previous studies have demonstrated systemic reductions in BP in
      both high stress populations and patients diagnosed with hypertension using this
      approach, but to the best of our knowledge, an investigation of their ability to
      produce immediate reductions in BP had not been published in the medical
      literature. The study was a randomized controlled design with 62 hypertensive
      participants who were divided into three groups. Group 1 was taking hypertensive
      medication, was taught self-regulation technique, and used heart rate variability
      coherence (HRVC) training devices. Group 2 was not yet taking medication and was
      trained in the same intervention. Group 3 was taking hypertensive medication but
      did not receive the intervention and was instructed to relax between the BP
      assessments. An analysis of covariates was conducted to compare the effectiveness
      of three different interventions on reducing the participants' BP. The use of the
      self-regulation technique and the HRVC-monitoring device was associated with a
      significantly greater reduction in mean arterial pressure in the two groups who
      used the intervention as compared with the relaxation-plus-medication group.
      Additionally, the group not taking medication that used the intervention also had
      a significantly greater reduction in systolic BP than the relaxation- plus
      medication group. These results suggest that self-regulation techniques that
      incorporate the intentional generation of positive emotions to facilitate a shift
      into the psychophysiological coherence state are an effective approach to
      lowering BP. This approach to reducing BP should be considered a simple and
      effective approach that can easily be taught to patients to quickly lower their
      BP in stressful situations. The technique should be especially useful when
      hypertensive patients are experiencing stressful emotions or reactions to
      stressors. It is possible that the BP reductions associated with the use of the
      technique leads to a change in the physiological set-point for homeostatic
      regulation of BP. Further studies should examine if large scale implementations
      of such heart-based coherence techniques could have a significant impact on
      reducing risk of mortality and morbidity in hypertensive patients. 

PMID- 24278822
TI  - Maps, "Big Data,"and Case Reports.

PMID- 24278824
TI  - News from around the world.

PMID- 24278823
TI  - Integrative medicine in america.

PMID- 24278825
TI  - Call for articles.

PMID- 24278826
TI  - The future of healthcare informatics: it is not what you think.
AB  - Electronic health records (EHRs) offer many valuable benefits for patient safety,
      but it becomes apparent that the effective application of healthcare informatics
      creates problems and unintended consequences. One problem that seems particularly
      challenging is integration. Painfully missing are low-cost, easy to implement,
      plug-and-play, nonintrusive integration solutions-healthcare's "killer app." Why
      is this? We must stop confusing application integration with information
      integration. Our goal must be to communicate data (ie, integrate information),
      not to integrate application functionality via complex and expensive application
      program interfaces (APIs). Communicating data simply requires a loosely coupled
      flow of data, as occurs today via email. In contrast, integration is a chief
      information officer's nightmare. Integrating applications, when we just wanted a
      bit of information, is akin to killing a gnat with a brick. 

PMID- 24278827
TI  - Clinical decision making-a functional medicine perspective.
AB  - As 21st century health care moves from a disease-based approach to a more patient
      centric system that can address biochemical individuality to improve health and
      function, clinical decision making becomes more complex. Accentuating the problem
      is the lack of a clear standard for this more complex functional medicine
      approach. While there is relatively broad agreement in Western medicine for what
      constitutes competent assessment of disease and identification of related
      treatment approaches, the complex functional medicine model posits multiple and
      individualized diagnostic and therapeutic approaches, most or many of which have
      reasonable underlying science and principles, but which have not been rigorously
      tested in a research or clinical setting. This has led to non-rigorous thinking
      and sometimes to uncritical acceptance of both poorly documented diagnostic
      procedures and ineffective therapies, resulting in less than optimal clinical
      care. 

PMID- 24278828
TI  - An application of cmaps in the description of clinical information structure and
      logic in electronic health records.
AB  - The development and implementation of competent and cost-effective computerized
      medical records that profoundly improve physician productivity and knowledge
      management will require the development of a new paradigm for the representation
      and analysis of medical knowledge and logic. Medical knowledge is acquired
      inductively by observing, measuring, and eliciting information from patients in a
      process that is investigational rather than transactional. Most, if not all,
      current approaches to health information technology (HIT) rely on a logic and
      data structure that imposes significant limitations on the ability of physicians
      to thoroughly and efficiently document and access empiric patient data because
      the information is almost invariably organized in a way which presumes, rather
      than makes explicit, the relationships of concepts and their meaning. Cmapping
      provides a graphical method of capturing and displaying expert content knowledge
      that is simple to comprehend and modify and provides a foundation for a dynamic,
      inductive, and inclusive method of clinical documentation and research. The basis
      of medical decision analysis along with representative samples of medical
      knowledge modeling in the Cmap format is presented. The knowledge structures that
      are captured in Cmaps can be expressed directly in propositional logic, enabling
      the capability to convert Cmapped clinical expressions to be used to define a
      description logic for clinical evidence documentation and analysis that can in
      turn be mapped to multiple natural languages. The described description logic
      approach can be used to formulate digital messages and documents and to automate
      the process of converting description specifications formulated in propositional
      logic into operational electronic health record solutions for capture and
      reporting of clinical encounters. It has also been demonstrated that using Cmaps
      to elicit content knowledge from physicians to build point-of-care clinical
      documentation screens can significantly reduce the time and costs necessary to
      implement the physician's knowledge into operational systems and that using Cmaps
      eliminates the need for HIT expertise in the rules-encoding process. 

PMID- 24278829
TI  - Physician Perspectives on Comparative Effectiveness Research: Implications for
      Practice-based Evidence.
AB  - Comparative effectiveness research (CER) is defined by the Institute of Medicine
      as "the generation and synthesis of evidence that compares the benefits and harms
      of alternative methods to prevent, diagnose, treat, and monitor a clinical
      condition or to improve the delivery of care." The goal of CER is to provide
      timely, useful evidence to healthcare decision makers including physicians,
      patients, policymakers, and payers. A prime focus for the use of CER evidence is
      the interaction between physician and patient. Physicians in primary practice are
      critical to the success of the CER enterprise. A 2009 survey suggests, however,
      that physician attitudes toward CER may be mixed-somewhat positive toward the
      potential for patient care improvement, yet negative toward potential restriction
      on physician freedom of practice. CER methods and goals closely parallel those of
      practice-based research, an important movement in family medicine in the United
      States since the 1970s. This article addresses apparent physician ambivalence
      toward CER and makes a case for family medicine engagement in CER to produce
      useful practice-based evidence. Such an effort has potential to expand care
      options through personalized medicine, individualized guidelines, focus on
      patient preferences and patient-reported outcomes, and study of complex
      therapeutic interventions, such as integrative care. Academic medical researchers
      will need to collaborate with experienced family physicians to identify
      significant practice-based research questions and design meaningful studies. Such
      collaborations would shape CER to produce high-quality practice-based evidence to
      inform family and community medicine. 

PMID- 24278830
TI  - International classification of traditional medicine.
AB  - The International Classification of Diseases (ICD) provides alphanumeric codes
      that have a longstanding place in the annals of contemporary medicine for
      epidemiology, health management, and clinical diagnoses from patient encounters
      to death certificates. This system is maintained by the World Health Organization
      (WHO). Traditional medicine (TM) has historical usage patterns established by
      treating people through the centuries but has never before been included in the
      ICD code set. The inclusion of traditional Asian medicine in the International
      Family of Classifications is a new venture and scheduled to be included in the
      ICD-11 revision of the codes. This may enable the comparison of diagnostic,
      clinical outcome, and epidemiological information across medical systems. WHO
      recently completed a survey among member nations and discovered that 82% of the
      world's population uses some form of TM.(2.) 

PMID- 24278832
TI  - Call for articles.

PMID- 24278831
TI  - Test result management in global health settings.
AB  - Across the globe, the ways in which patients' test results are managed are as
      varied as the many different types of healthcare systems that manage these data.
      The outcomes, however, are often not too dissimilar: too many clinically
      significant test results fall through the cracks. The consequences of not
      following up test results in a timely manner are serious and often devastating to
      patients: diagnoses are delayed, treatments are not initiated or altered in time,
      and diseases progress. In resource-poor settings, test results too commonly get
      filed away within the paper chart in ways that isolate them and prevent passage
      to future providers caring for a patient. To make matters worse, the onus to act
      upon these test results often rests on patients who need to return to the clinic
      within a specified timeframe in order to obtain their results but who may not
      have the means or are too ill to do so. Even in more developed healthcare
      settings that use electronic records, clinical data residing in the electronic
      medical record (EMR) are often stubbornly "static"-key pieces of clinical
      information are frequently not recognized, retrieved, or shared easily. In this
      way, EMRs are not unlike paper record systems, and therefore, EMRs alone will not
      solve this problem. To illustrate this problem, consider the case of a patient
      newly diagnosed with HIV in 3 different healthcare delivery settings. 

PMID- 24278833
TI  - Psoriatic arthritis.
AB  - Autoimmune diseases (ADs) are chronic, often debilitating and potentially life
      threatening conditions that collectively affect up to 23.5 million Americans, and
      their incidence is rising.(1) They are heterogeneous in pathology but share
      common etiopathogenic factors such as intestinal hyperpermeability.(2) Although
      up to 100 ADs have been identified, there are likely more.(1) Genetics plays a
      clear role in the predisposition for the development and phenotype of AD, but
      various combinations of factors, such as toxins, endogenous hormone imbalances,
      microbes (including of GI origin), infections, stress and food antigens, are
      involved in disease expression.(2-5) Standard treatments include NSAIDs,
      steroids, antineoplastic agents and tumor necrosis factor-alpha antagonists.
      These tools have potentially devastating side effects and are often applied
      regardless of the diagnosis. Frequently, they are only modestly effective in
      relieving symptoms and limiting the advancing disease process. Direct health-care
      costs of AD are estimated at around 100 billion dollars per year in the United
      States. By comparison, cancer care costs about 57 billion dollars per year.(1)
      The rising incidence of this debilitating and costly group of conditions dictates
      that safe, alternative approaches to treatment be considered now. 

PMID- 24278835
TI  - Treatment of anxiety and stress with biofeedback.
AB  - "Kate" is a thin, attractive 50-year-old perimenopausal woman who considers
      herself "basically healthy" but feels she needs help with stress management in
      her life. She is educated, married, and the mother of 4 children ranging in age
      from 11 to 22 years. In addition to managing her household, she has a full-time
      job as an administrative assistant and also works a part-time job from home. She
      states she needs to do this so the family can "get back on our feet" as her
      husband was unemployed for a number of months and they currently have 2 children
      in college. In addition, they relocated a year ago to Pittsburgh, Pennsylvania,
      for her husband's job and now have a higher mortgage payment. "Family" is Kate's
      top priority, but she does not receive much assistance from her husband on the
      home front and feels "there is not enough time in a day." 

PMID- 24278834
TI  - Autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) are collectively the most commonly diagnosed
      pediatric neurodevelopmental condition. ASDs include autism, pervasive
      developmental disorder-not otherwise specified (PDD-NOS), Rett syndrome and
      Asperger disorder. ASD is characterized by impaired communication and social
      interaction and may involve developmental delays and seizure disorders. Recent
      parent-reported diagnosis of ASD in the United States put it at higher levels
      (1:91) than previously thought, with its diagnosis in boys occurring 4 to 5 times
      more frequently than in girls (1:58).(1) CDC estimates are currently 1:110;(1) up
      from 1:150 in 2007.(2) Annual medical expenditures for those affected are
      generally four to six times greater than for those without ASD.(1) While twin
      studies demonstrate that genetics play a significant role in ASD, the impact of
      environment should not be underestimated, given the approximate 20-fold increase
      in incidence over the last 20 years.(3.) 

PMID- 24278836
TI  - The Effects of Tetrahydro-iso-alpha Acids and Niacin on Monocyte-Edothelial Cell
      Interactions and Flow-mediated Vasodilation.
AB  - Niacin favorably modifies cardiovascular risk factors but is associated with
      flushing and shows limited benefit in improving endothelial function. We
      investigated whether combining anti-inflammatory tetrahydro-iso-alpha acids
      (THIAA) from hops with niacin would improve endothelial function. We hypothesized
      that the THIAA+niacin combination would demonstrate benefits not seen with niacin
      alone. In an in vitro model, a THIAA+niacin mixture inhibited several TNF-alpha
      induced cytokines in human aortic endothelial cells and in human monocytic cells
      and was significantly more efficacious than niacin alone. Subsequently, the
      effect of 125 mg THIAA and 500 mg niacin on endothelial-regulated flow-mediated
      vasodilation (FMD) was explored in a pilot study of 11 dyslipidemic volunteers.
      The 12-week treatment (2 tablets/day) resulted in a clinically relevant FMD
      increase compared to a trend toward an FMD decrease with placebo; the between-arm
      difference was statistically significant. THIAA+niacin treatment also improved
      total cholesterol, low-density lipoprotein cholesterol, and uric acid. No
      significant improvement in these parameters was observed with placebo. High
      sensitivity C-reactive protein was significantly increased only in the placebo
      arm. Nutritional support with a THIAA+niacin combination may provide benefits for
      endothelial function in those with dyslipidemia. 

PMID- 24278837
TI  - Global advances in health and medicine through systems biology: an example from
      the Netherlands.
AB  - Globally, healthcare systems are facing problems with increasing healthcare costs
      due to chronic diseases. Cardiovascular disease, cancer, diabetes, depression,
      and chronic lung disease are some of the top chronic diseases that put pressure
      on our healthcare systems and are very difficult to resolve. The chronic diseases
      mentioned are often lifestyle-related and require a personalized approach. The
      solutions that we currently have at hand seem to be insufficient in meeting the
      needs of the patients and of our healthcare systems: the cracks in our systems
      are showing. Patients with chronic illness and multimorbidity find themselves
      caught in a web of referrals between medical specialists and conflicting
      treatment plans. As a result, they are consuming a lot of healthcare without
      actually reaching their goal: attaining the most optimal quality of life and the
      least physical burden possible. In short, mechanisms that previously functioned
      perfectly must now be replaced by new approaches. The supply of the healthcare
      system no longer meets the demands of society. 

PMID- 24278838
TI  - Treatment of multiple sclerosis with chinese scalp acupuncture.
AB  - Chinese scalp acupuncture is a contemporary acupuncture technique with just 40
      years of history. It integrates traditional Chinese needling methods with Western
      medical knowledge of the cerebral cortex and has been proven to be a very
      effective technique for treating multiple sclerosis (MS) and other central
      nervous system disorders. A 65-year-old male patient who had had MS for 20 years
      was treated with Chinese scalp acupuncture. The motor area, sensory area, foot
      motor and sensory area, balance area, hearing and dizziness area, and tremor area
      were stimulated once a week for 10 weeks, then once a month for six sessions.
      After the 16 treatments, the patient showed remarkable improvements. He was able
      to stand and walk without any problems. The numbness and tingling in his limbs
      did not bother him anymore. He had more energy and had not experienced
      incontinence of urine or dizziness after the first treatment. He was able to
      return to work full time. At this writing, the patient has been in remission for
      26 months. This case demonstrates that Chinese scalp acupuncture can be a very
      effective treatment for patients with MS. Chinese scalp acupuncture holds the
      potential to expand treatment options for MS in both conventional and
      complementary or integrative therapies. It can not only relieve symptoms,
      increase the patient's quality of life, and slow and reverse the progression of
      physical disability but also reduce the number of relapses and help patients with
      multiple sclerosis to remain in remission. 

PMID- 24278839
TI  - Kampo Extract of Shinbuto Improved Refractory Diarrhea in Milroy's Disease.
AB  - Milroy's disease is a hereditary congenital lymphedema caused by lymphatic
      obstruction. The legs are most commonly affected, but impaired intestinal
      lymphatic flow can cause loose bowel movements. Here, we report the use of the
      Kampo extract of shinbuto for successful treatment of and abdominal pain in a
      patient with Milroy's disease. Milroy's disease was diagnosed because of left leg
      lymph-edema with onset at birth. Conservative therapy with a compression bandage
      was applied. However, when the patient moved to Manila at 35 years of age, she
      was exposed to drastic temperature changes between the air-conditioned cold
      environment in her room and the hot and humid environment outside. She developed
      a constitutional state of coldness as in hiesho (?). Then sudden lower abdominal
      pain and diarrhea began to occur 3 times per week and lasted at least 1 hour,
      sometimes accompanied by vomiting. It happened particularly when she was exposed
      to the cold environment and was not related to meals. Conventional anti
      cholinergic or antidiarrhetic drugs had no therapeutic effect. These attacks
      continued in the same frequency for 3 years, so the patient visited a Kampo
      (traditional Japanese medicine) clinic, where her diagnosis of Milroy's disease
      associated diarrhea and abdominal pain was augmented by the Kampo diagnosis of
      hiesho, suitai (body fluid retention). She was prescribed 7.5 g of shinbuto
      extract per day (TJ-30; Tsumura Co, Tokyo, Japan). The shinbuto extract
      significantly reduced abdominal pain and refractory diarrhea to about 2 days per
      month, and it tapered off completely in 3 months. Shinbuto is usually used
      against cold-induced diarrhea. Rewarming and water movement by shinbuto resulted
      in significant improvement in symptoms induced by hiesho and suitai triggered by
      the cold environment, though the patient's leg swelling did not change. 

PMID- 24278840
TI  - Cardiac tamponade presenting as refractory asthma.
AB  - Asthma has numerous etiologies, and successful treatment requires a proper
      diagnosis. Changes in weather and exposure to dust can make treatment of asthma
      difficult. This case exemplifies a diagnostic dilemma associated with
      bronchospasm; bronchospasm can have an occult cardiac etiology. Diagnosis can be
      particularly challenging in rural sub-Saharan Africa during the Harmattan, when
      winds are blowing sands from the Sahara into nearby villages, especially when
      radiographs are not available. This case is that of a 40-year-old female Ghanaian
      woman with a lifelong history of asthma. Although she has often had exacerbations
      of bronchospasm during the dusty Harmattan season, her bronchospasm was now
      refractory to usual treatments. X-rays were not available at the clinic in the
      rural city of Tamale, Ghana, and bedside ultrasound was utilized. She was found
      to have cardiac tamponade with secondary "cardiac asthma." After 750 cc of fluid
      was aspirated during a bedside pericardiocentesis, her bronchospasm immediately
      resolved. The cardiac effusion was due to previously unknown renal failure from
      hyper-tension. The patient was referred for dialysis and 1 year later was well
      without any recurrence of significant cardiac effusions. Healthcare providers
      should be wary of atypical non-pulmonary etiologies of bronchospasm, especially
      in cases where there is an inadequate response to usual treatment. Bedside
      ultrasound has great utility for the diagnosis of cardiac tamponade. 

PMID- 24278841
TI  - Patient-centered Diabetes Care in Children: An Integrated, Individualized,
      Systems-oriented, and Multidisciplinary Approach.
AB  - BACKGROUND: Type 1 diabetes mellitus in children is associated with various
      medical, psychological, emotional, social, and organizational hurdles. Patient
      centered disease management should address all patient-relevant issues in an
      individualized, systems-oriented, and multidisciplinary approach. CASE: A 10-year
      old girl with type 1 diabetes mellitus, a developmental disorder with motor and
      sensory dysfunction and dyscalculia was cared for full-time by her mother and an
      assistant nurse. Receiving standard intensified insulin therapy, she still had
      poor glucose control with frequent mild and severe hypoglycemic episodes. She was
      socially isolated and not able to attend peer activities and was frustrated with
      her situation. The mother was substantially stressed, and the child-mother
      relationship was endangered. The girl and her family were referred to an
      integrated, patient-centered, and highly individualized, multidisciplinary
      diabetic care program that offered self-management education courses and
      psychosomatic care. A core element was to switch the main focus from technical
      management and laboratory data to the girl and her specific problems, wishes,
      goals, needs, and conditions. The child became an active partner in management
      and decisions. The program offered age-appropriate activities. Consequently, the
      girl was able to successively self-manage her disease, resulting in a substantial
      improvement in glucose control, quality of life, satisfaction, and the
      relationship between mother and daughter. CONCLUSION: Increasing technical
      sophistication in diabetes management tends to lay the focus on biomedical
      outcomes. Improved medical and psychosocial results may be achieved when the
      patient and his or her needs, hurdles, goals, and psychological and social issues
      are made central to the care he or she receives.

PMID- 24278842
TI  - Self-directed Mindfulness Training and Improvement in Blood Pressure, Migraine
      Frequency, and Quality of Life.
AB  - BACKGROUND: Interest in case studies has undergone a resurgence concurrent with
      increasing prioritization of illustrations of patient-centered care. However,
      substantial inclusion of the patient in these reports remains limited. Here, a
      doctor and patient collaborate to present her case report of self-directed
      mindfulness training and the subsequent changes in blood pressure, migraine
      frequency, and quality of life. METHODS: After receiving encouragement from her
      naturopathic doctor, the patient initiated an 8-week program in mindfulness
      training following the Kabat-Zinn protocol and logged her daily blood pressure
      and symptoms before and after meditation sessions over an 11-week period.
      RESULTS: Patient-reported outcomes included decreased perceived stress, increased
      focus, and a newfound sense of centeredness and calm. Changes in objective
      outcomes were clinically and statistically significant, including reductions in
      mean systolic and diastolic blood pressure between week 1 and week 11 (P = .0001
      and P = .0004 for systolic and diastolic, respectively, by paired, 2-sided t
      tests). Self-reported frequency of chronic migraine was also reduced. Critical to
      the patient's success was that mindfulness training was first approached in a
      simple, accessible manner prior to embarking on a deeper, extended experience.
      DISCUSSION AND CONCLUSION: Self-directed mindfulness training can have a
      meaningful impact on both subjective and objective health outcomes. It may take
      years of encouragement from a healthcare provider before a patient is ready to
      adopt a mind-body practice; it is important to recognize and counsel patients
      with messages appropriate to their stage of change and self-efficacy.
      Additionally, case studies that combine the voice of the clinician and the
      patient can provide useful illustrations of truly patient-centered care.

PMID- 24278843
TI  - Health coaching interventions with a heart-healthy lenoir project client.
AB  - The Heart-Healthy Lenoir Project is a multi-study project designed to reduce the
      risk burden of heart disease in Lenoir County, North Carolina. This case report
      examines one client's experience in this project and the impact of health
      coaching interventions that were used. The client presented with unhealthy
      lifestyle behaviors and a systolic blood pressure (BP) of more than 200 mmHg.
      After 1 year of educational group meetings and personalized health coaching, the
      client was able to reduce her BP to an acceptable range and has adopted many new
      lifestyle behaviors. This case report demonstrates one way health coaching is
      being integrated into educational programs and in collaboration with primary care
      practices. 

PMID- 24278844
TI  - Case report of hemoglobin a1c and weight reduction in integrative health
      coaching.
AB  - Integrative health coaching (IHC) offers significant health improvement in
      biometric measures without pharmaceuticals. In this case of newly diagnosed
      impaired glucose tolerance (IGT) with obesity, IHC used the patient's strengths
      to reverse IGT, prevent frank diabetes, and reduce weight by 40 lbs or 21% of her
      original weight. This intervention included a client self-assessment and 14 in
      person health coaching sessions over 11 months. IHC provides a framework to
      accomplish short-term goals and identify and overcome barriers while drawing on
      the strengths and aims of the individual. 

PMID- 24278845
TI  - Health coaching integration into primary care for the treatment of obesity.
AB  - Obesity (and its related comorbidities) is one of the fastest-growing health
      concerns facing the United States and shows no sign of abating.(1) The Centers
      for Disease Control and Prevention calculated that nearly 36% of American adults
      were obese in 2010 and estimates that this number will reach 44% by 2018. The
      current standard of care for the management of patients with obesity in primary
      care is often a general recommendation by the physician to lose weight through
      improved nutrition and increased physical activity. Educational materials may be
      provided along with a referral to a dietician, nutritionist, or weight management
      program. Health coaching as an obesity intervention has yet to be fully
      integrated into primary care practice but has proven to be effective in corporate
      wellness and behavioral weight loss programs.(2) (-) (5.) 

PMID- 24278846
TI  - Wellness coaching outcomes in a case report of a diabetic native american male.
AB  - Medically referred wellness coaching clients may present thinking patterns that
      generate internal resistance to change, including lack of urgency, inadequate
      incentives, and uncertainty about what they need to do differently.(1) Applying
      the Wellcoaches (Wellcoaches Corp, Wellesley, Massachusetts) model interventions
      within a framework of the four domains of learning (cognitive, affective,
      behavioral, and conative)2 can enhance wellness coaching outcomes. This case
      report reviews wellness coaching outcomes with a 44-year-old single male tribal
      member of a Midwest Native American tribe who recently had been diagnosed with
      diabetes. Challenges presented by resistance to change and a discussion of the
      four domains of learning applied to wellness coaching are also reported. 

PMID- 24278847
TI  - Wellness coaching for obesity: a case report.
AB  - D.S. presented to a medical and surgical weight-loss program to initiate
      bariatric surgery. He had made numerous attempts at weight loss to no avail and
      was taking steps toward bariatric surgery as a last viable option. D.S.'s health
      insurance provider required 3 months of supervised weight loss prior to approval
      for surgery, and this was initiated with a board-certified bariatrician (MD) and
      a registered dietitian nutritionist (RDN)/wellness coach. D.S. presented with a
      body mass index (BMI) >40 and was classified as morbidly obese with comorbidities
      of high cholesterol and hyperglycemia and degenerative joint disease (DJD) of the
      knees. D.S. began the process outlined by his insurance company, meeting with the
      MD and RDN/wellness coach monthly. A plan was developed by D.S. and his
      RDN/wellness coach that alligned with his wellness vision, values, and lifestyle.
      D.S. ate meals and snacks at regular intervals throughout the day, consumed
      little to no red meat, increased his consumption of fruits and vegetables, and
      spent 1 hour daily in a swimming pool-walking, swimming, or both. By the end of
      the 3-month period required by the insurance provider, D.S. had lost more than 30
      lbs, improved his exercise capacity, no longer used a cane, and chose to continue
      with coaching rather than undergo bariatric surgery. D.S. continued to meet with
      the MD and RDN monthly for 1 year and averaged a 10-lb weight loss per month for
      a total of 120 lbs, normalizing his blood panels and improving his joint
      mobility. D.S. continued to meet with the RDN/wellness coach for a total of 10
      visits during year 2 and quarterly visits through year 3. D.S. lost a total of
      240 lbs, maintained the weight loss over the 3-year period, and achieved these
      results solely through lifestyle interventions. Although bariatric surgery is a
      viable treatment option for class 2 and 3 obesity, many patients pursue this
      treatment option without the help of medical and commercial weight loss personnel
      to improve the likelihood of weight loss sustainability. The investment of
      lifestyle intervention in this circumstance was less than $5000 (exculsive of
      blood panels) compared with the $20 000 cost of bariatric surgery at the time of
      intervention. 

PMID- 24278848
TI  - Personalized health planning with integrative health coaching to reduce obesity
      risk among women gaining excess weight during pregnancy.
AB  - Health coaching is an emerging behavioral intervention to improve outcomes in
      chronic disease management and prevention; however, no studies have investigated
      its utility in postpartum women who have gained excess weight during pregnancy. A
      32-year-old primigravida woman who was overweight at conception and gained 23 lbs
      more than Institute of Medicine recommendations for her pre-pregnancy body mass
      index participated in a 6-month personalized health planning with integrative
      health coaching (PHPIHC) intervention. The intervention included a baseline
      health risk assessment review with a healthcare provider and eight biweekly, 30
      minute telephonic health coaching sessions. The participant demonstrated
      improvement in physical activity, energy expenditure, knowledge, and confidence
      to engage in healthpromoting behaviors. Although the participant did not reach
      the target weight by completion of the health coaching sessions, follow up 8
      months later indicated she achieved the target goal (within 5% of prepregnancy
      weight). This case report suggests that PHP-IHC can support postpartum women in
      returning to pre-pregnancy weight after gaining excess gestational weight. Future
      research and clinical trials are needed to determine the best timing, length, and
      medium (online, in-person, telephonic) of PHP-IHC for postpartum women. 

PMID- 24278849
TI  - Mentoring interdisciplinary research teams for the study of sex and gender
      differences in health and disease.
AB  - Initiatives to hasten the translation of basic science discoveries to clinical
      care have necessitated the development of new approaches to interdisciplinary
      collaboration and training of future investigators. This has been nowhere more
      important than in the study of sex differences with implications for extension
      into areas of gender medicine. Clearly, gaining better understanding of the role
      that sex and gender play in health and disease is essential to the implementation
      of truly individualized medicine. This case report will describe our experiences
      in developing the Mayo Clinic Building Interdisciplinary Research Programs in
      Women's Health (BIRCWH) program, an interdisciplinary research and training
      program in women's health and sex and gender differences. We identify both our
      successes and the barriers we have encountered in order that others who are
      developing similar programs might benefit from our experiences. 

PMID- 24278850
TI  - Pre-operative serum albumin and neutrophil-lymphocyte ratio are associated with
      prolonged hospital stay following colorectal cancer surgery.
AB  - AIMS: Colorectal cancer is the third most common cancer in European populations.
      It has been shown previously that neutrophil-lymphocyte ratio (NLR), pre
      operative albumin, and haemoglobin are useful prognostic indicators. The aim of
      this study was to assess how these factors influence the length of postoperative
      stay (LOS) following colorectal cancer surgery. METHODOLOGY: All patients
      undergoing elective colorectal resections for malignancy between 2010 and 2011 in
      Pilgrim Hospital, Boston, U.K. were considered for the study. Hospital archive
      systems were used to ascertain pre-operative NLR, albumin and haemoglobin levels.
      LOS was calculated from electronic discharge documents with day 1 being the day
      after surgery. Unifactorial and multifactorial analyses were performed to
      identify independent predictors of prolonged stay. RESULTS: 196 patients were
      included in the study. Pre-operative haemoglobin was not associated with
      prolonged hospital stay. On univariate analysis, pre-operative serum albumin and
      pre-operative NLR were associated with prolonged hospital stay. On multivariate
      analysis, pre-operative serum albumin >34.5 g/dl (odds ratio, 0.47; 95%
      confidence interval, 0.24 - 0.92; p = 0.027) retained independent association for
      prolonged hospital stay .However, pre-operative NLR failed to reach statistical
      significance on multivariate analysis. CONCLUSIONS: Patients with low albumin and
      elevated NLR are more likely to have an increased hospital stay following
      colorectal cancer surgery. This may be useful for surgeons in terms of
      identifying the 'high-risk' patient post-operatively and allow for early
      intervention.

PMID- 24278851
TI  - Anal cancer study based on Korea central cancer registry data: one step forward
      in clinical research.

PMID- 24278852
TI  - Additional chemotherapy during resting periods after preoperative
      chemoradiotherapy in patients with rectal cancer.

PMID- 24278853
TI  - Histopathology and physiological alterations after procedure for prolapsed
      hemorrhoids.

PMID- 24278854
TI  - Mesenteric embolization: is it safe in patients with acute lower gastrointestinal
      hemorrhage?

PMID- 24278855
TI  - Characteristics and survival of korean anal cancer from the Korea central cancer
      registry data.
AB  - PURPOSE: In Korea, anal cancer is rare disease entity with specific clinical
      characteristics. Therefore, no survival analysis with a sufficient patient
      population has been performed. The aim of this study was to evaluate the
      characteristics of Korean anal cancer, focusing on the survival according to
      tumor histologies, sex, and a specific age group, using the nationwide cancer
      registry. METHODS: Using the Korea Central Cancer Registry, we analyzed a total
      of 2,552 cases from 1993 to 2010. We assessed the 5-year relative survival by
      using tumor histology. In addition, survival differences of Surveillance
      Epidemiology and End Results (SEER) stage were analyzed for both sexes and for
      young-age cancer (younger than 40 years) and advanced-age cancer (older than 70
      years). RESULTS: The 5-year relative survival among anal cancer patients
      increased from 38.9% for the period 1993-1995 to 65.6% for the period 2006-2010.
      The anal squamous cell carcinoma was the most common histology and showed better
      survival than other types of cancer. Females demonstrated better survival than
      males in all SEER stages. The 5-year survivals for patients in whom anal cancer
      developed before the age of 40 and at or after the age of 40 were 62.4% and
      51.6%, respectively. The 5-year survival for patients in whom cancer developed at
      or after the age of 70 was much worse than that for patients in whom the cancer
      had developed prior to that age. CONCLUSION: Korean anal cancer has certain
      distinctive characteristics of survival according to tumor histology, sex, and
      age. Despite limitations on available data, this study used the nationwide
      database to provide important information on the survival of Korean patients with
      anal cancer.

PMID- 24278856
TI  - Knowledge of and practice patterns for hereditary colorectal cancer syndromes in
      korean surgical residents.
AB  - PURPOSE: Obtaining a detailed family history through detailed pedigree is
      essential in recognizing hereditary colorectal cancer (CRC) syndromes. This study
      was performed to assess the current knowledge and practice patterns of surgery
      residents regarding familial risk of CRC. METHODS: A questionnaire survey was
      performed to evaluate the knowledge and the level of recognition for analyses of
      family histories and hereditary CRC syndromes in 62 residents of the Department
      of Surgery, Seoul National University Hospital. The questionnaire consisted of 22
      questions regarding practice patterns for, knowledge of, and resident education
      about hereditary CRC syndromes. RESULTS: Two-thirds of the residents answered
      that family history should be investigated at the first interview, but only 37%
      of them actually obtained pedigree detailed family history at the very beginning
      in actual clinical practice. Three-quarters of the residents answered that the
      quality of family history they obtained was poor. Most of them could diagnose
      hereditary nonpolyposis colorectal cancer and recommend an appropriate
      colonoscopy surveillance schedule; however, only 19% knew that cancer
      surveillance guidelines differed according to the family history. Most of our
      residents lacked knowledge of cancer genetics, such as causative genes, and
      diagnostic methods, including microsatellite instability test, and indicated a
      desire and need for more education regarding hereditary cancer and genetic
      testing during residency. CONCLUSION: This study demonstrated that surgical
      residents' knowledge of hereditary cancer was not sufficient and that the quality
      of the family histories obtained in current practice has to be improved. More
      information regarding hereditary cancer should be considered in education
      programs for surgery residents.

PMID- 24278857
TI  - A Phase II Study of Additional Four-Week Chemotherapy With Capecitabine During
      the Resting Periods After Six-Week Neoadjuvant Chemoradiotherapy in Patients With
      Locally Advanced Rectal Cancer.
AB  - PURPOSE: The aim of this study is to evaluate the efficacy and the safety of
      additional 4-week chemotherapy with capecitabine during the resting periods after
      a 6-week neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced
      rectal cancer. METHODS: Radiotherapy was delivered to the whole pelvis at a total
      dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825
      mg/m(2) twice daily for 10 weeks. Surgery was performed 2-4 weeks following the
      completion of chemotherapy. RESULTS: Between January 2010 and September 2011, 44
      patients were enrolled. Forty-three patients underwent surgery, and 41 patients
      completed the scheduled treatment. Pathologic complete remission (pCR) was noted
      in 9 patients (20.9%). T down-staging and N down-staging were observed in 32
      patients (74.4%) and 33 patients (76.7%), respectively. Grade 3 to 5 toxicity was
      noted in 5 patients (11.4%). The pCR rate was similar with the pCR rates obtained
      after conventional NCRT at our institute and at other institutes. CONCLUSION:
      This study showed that additional 4-week chemotherapy with capecitabine during
      the resting periods after 6-week NCRT was safe, but it was no more effective than
      conventional NCRT.

PMID- 24278858
TI  - Correlation of histopathology with anorectal manometry following stapled
      hemorrhoidopexy.
AB  - PURPOSE: The removal of smooth muscle during stapled hemorrhoidopexy raises
      concerns regarding its effects on postoperative anorectal function. The purpose
      of this study was to evaluate the correlation between the amount of muscle
      removed and changes in anorectal manometry following stapled hemorrhoidopexy.
      METHODS: Patients with symptomatic II, III, or IV degree hemorrhoids that
      underwent stapled hemorrhoidopexy between January 2008 and May 2011 were included
      in this study. Anorectal manometry was performed preoperatively and at three
      months postoperatively. The resected doughnuts were examined histologically, and
      the thicknesses of muscle fibers were evaluated. RESULTS: Eighty-five patients
      (34 males) with a median age of 47 years were included. Muscularis propria fibers
      were identified in 63 of 85 pathologic specimens (74.1%). The median thickness of
      the muscle fibers was 1.58 +/- 1.21 mm (0 to 4.5 mm). The mean resting pressure
      decreased by approximately 7 mmHg after operation in the 85 patients (P = 0.019).
      In patients with muscle incorporation, there was a significant difference in mean
      resting pressure (P = 0.041). In the analysis of the correlation of the
      difference in anorectal manometry results ([the result of postsurgical anorectal
      manometry] - [the result of presurgical anorectal manometry]) to the thickness of
      muscle fibers, no significant differences were seen. No patients presented with
      fecal incontinence. CONCLUSION: Although the incidence of fecal incontinence is
      very low, muscle incorporation in the resected doughnuts following stapled
      hemorrhoidopexy may affect anorectal pressure. Therefore, surgeons should
      endeavor to minimize internal sphincter injury during stapled hemorrhoidopexy.

PMID- 24278859
TI  - The safety and efficacy of mesenteric embolization in the management of acute
      lower gastrointestinal hemorrhage.
AB  - PURPOSE: Mesenteric embolization is an integral part in the management of acute
      lower gastrointestinal (GI) bleeding. The aim of this study was to highlight our
      experience after adopting mesenteric embolization in the management of acute
      lower GI hemorrhage. METHODS: A retrospective review of all cases of mesenteric
      embolization for acute lower GI bleeding from October 2007 to August 2012 was
      performed. RESULTS: Twenty-seven patients with a median age of 73 years (range,
      31 to 86 years) formed the study group. More than half (n = 16, 59.3%) of the
      patients were on either antiplatelet and/or anticoagulant therapy. The underlying
      etiology included diverticular disease (n = 9), neoplasms (n = 5) and
      postprocedural complications (n = 6). The colon was the most common bleeding site
      and was seen in 21 patients (left, 10; right, 11). The median hemoglobin prior to
      the embolization was 8.6 g/dL (6.1 to 12.6 g/dL). A 100% technical success rate
      with immediate cessation of hemorrhage at the end of the session was achieved.
      There were three clinical failures (11.1%) in our series. Two patients re-bled,
      and both underwent a successful repeat embolization. The only patient who
      developed an infarcted bowel following embolization underwent an emergency
      operation and died one week later. There were no factors that predicted clinical
      failure. CONCLUSION: Mesenteric embolization for acute lower GI bleeding can be
      safely performed and is associated with a high clinical success rate in most
      patients. A repeat embolization can be considered in selected cases, but
      postembolization ischemia is associated with bad outcomes.

PMID- 24278860
TI  - Giant ascending colonic diverticulum presenting with intussusception.
AB  - Diverticular disease of the colon is a common disease, and its incidence is
      increasing gradually. A giant colonic diverticulum (GCD) is a rare entity and is
      defined as a diverticulum greater than 4 cm in size. It mainly arises from the
      sigmoid colon, and possible etiology is a ball-valve mechanism permitting
      progressive enlargement. A plain abdominal X-ray can be helpful to make a
      diagnosis initially, and a barium enema and abdominal computed tomography may
      confirm the diagnosis. Surgical intervention is a definite treatment for a GCD.
      We report a case of an ascending GCD presenting with intussusception in a young
      adult. 

PMID- 24278862
TI  - A new start.

PMID- 24278861
TI  - Acute cholecystitis after a colonoscopy.
AB  - Acute cholecystitis after a colonoscopy is a rare event, and only eight
      documented cases are reported in the literature. A 35-year-old male underwent a
      screening colonoscopy. There was a 5-mm sessile polyp in the sigmoid colon, which
      was removed by using a hot snare polypectomy. Forty-eight hours after the
      colonoscopy, the patient visited our emergency department with epigastric pain
      and fever. Based on the clinical findings, laboratory data and radiologic
      imaging, our diagnosis was acute cholecystitis. Because no previous cases of this
      type have been reported to date in Korea, we publish the details of our patients
      who presented with a postcolonoscopy complication diagnosed as acute
      cholecystitis. 

PMID- 24278864
TI  - Treadmill exercise improves behavioral outcomes and spatial learning memory
      through up-regulation of reelin signaling pathway in autistic rats.
AB  - Autism is a complex neurodevelopmental disability with impairments of social
      interaction and communication, and repetitive behavior. Reelin is an
      extracellular glycoprotein that is essential for neuronal migration and brain
      development. Neuroprotective effects of exercise on various brain insults are
      well documented, however, the effects of exercise on autism in relation with
      reelin expression are not clarified. In the present study, we investigated the
      effects of treadmill exercise on the functional recovery and on the expressions
      of reelin and its downstream molecules, phosphatidylinositol-3-kinase (PI3K),
      phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated protein
      kinase 1 and 2 (p-ERK1/2), using autistic rats. For the induction of autism-like
      animal model, 400 mg/kg valproic acid was subcutaneously injected into the rats
      on the postnatal day 14. The rat in the treadmill exercise groups were forced to
      run on a treadmill for 30 min once a day, five times a week for 4 weeks, starting
      postnatal day 28. To investigate autism-like behaviors and memory deficit, open
      field, social interaction, and radial 8-arm maze were performed.
      Immunohistochemistry and western blotting were conducted. In the present results,
      treadmill exercise alleviated aggressive tendency and improved correct decision
      in the spatial learning memory in the autistic rats. Treadmill exercise increased
      neurogenesis and the expressions of reelin and its down-stream molecules, PI3K, p
      Akt, and p-ERK1/2, in the hippocampus of the autistic rats. The present study
      showed that treadmill exercise ameliorated aggressive behavior and improved
      spatial learning memory through activation of reeling signaling pathway in the
      valproic acid-induced autistic rats. 

PMID- 24278863
TI  - Effects of aging and exercise training on apoptosis in the heart.
AB  - Aging is characterized by a progressive decline in cardiac function. A critical
      contributor to the age-related impairment in cardiac function is the loss of
      cardiac myocytes through "apoptosis", or programmed cell death. Structural
      remodeling in the heart with advancing age includes (a) loss of cardiomyocytes,
      (b) reactive hypertrophy of the remaining cardiomyocytes, and (c) increased
      connective tissue and altered geometry. The loss of cardiomyocytes with aging
      occurs through apoptosis. Particularly, mitochondrial-mediated apoptotic pathway
      is the best characterized and believed critical in regulating apoptosis with
      aging, suggesting that mitochondria are very important sites of programmed cell
      death. It has been also reported that mitochondrial dysfunction, oxidative
      stress, and impaired stress response contribute to age-induced mechanical
      remodeling as well as apoptosis. In contrast, exercise training not only improves
      cardiac function, but also reduces the risk of heart disease. We recently found
      that aging increased mitochondrial-mediated apoptotic signaling and apoptosis in
      the left ventricle, while chronic exercise training was effective in diminishing
      mitochondrial-mediated apoptotic signaling pathways in the aging heart, as
      indicated by lower DNA fragmentation, terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL)-positive staining, and caspase-3
      cleavage, when compared with left ventricles from the age-matched sedentary
      group. In this review, we will provide a comprehensive update regarding the
      effects of aging and exercise training on apoptosis in the heart. 

PMID- 24278865
TI  - Functional effect of mouse embryonic stem cell implantation after spinal cord
      injury.
AB  - We transplanted mouse embryonic stem cells (mESCs) to improve functional loss in
      a rat model of clip-compression spinal cord injury (SCI). The mouse embryonic
      stem cells were transplanted to injured cord 7 days after injury. We include
      minimizing the progression of secondary injury, manipulating the neuroinhibitory
      environment of the spinal cord, replacing lost tissue with transplanted cells and
      substantial improvement of motor. A number of potential approaches optimize
      functional recovery after spinal cord injury. We review the application of stem
      cell transplantation to the spinal cord, emphasizing the use of embryonic stem
      cells for reconstruction of spinal cord injury. Thus, this study provides strong
      evidence to support that transplantation of mESC could improve functional
      recovery after SCI. 

PMID- 24278866
TI  - Treadmill exercise exerts ameliorating effect on isolation-induced depression via
      neuronal activation.
AB  - Maternal isolation has been used as a valid animal model of early life stress,
      and it induces depression to offspring. Exercise ameliorates the incidence and
      severity of stress-related mood disorders, such as depression and anxiety. Here
      in this study, we investigated the effects of treadmill exercise on brain
      neuronal excitation in the rat pups with maternal isolation-induced depression.
      Forced swimming test and immunohistochemistry for glucocorticoid receptor and c
      Fos in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus
      were conducted. Maternal isolation lasted for 6 hours per day and was continued
      from postnatal day 1 to postnatal day 30. The rat pups in the exercise group were
      forced to run on a treadmill for 30 min once a day for 10 consecutive days,
      starting from the postnatal day 21 until the postnatal day 30. In the present
      results, treadmill exercise alleviated depressive state in the maternal separated
      rat pups, as potently as fluoxetine treatment. Treadmill exercise also restored
      the expressions of glucocorticoid receptor and c-Fos in the hippocampal dentate
      gyrus and hypothalamic paraventricular nucleus of the maternal separated rat pups
      near to the control level, as fluoxetine treatment. The present study suggests
      the possibility that treadmill exercise can be used as the therapeutic strategy
      for the childhood depression induced by disturbed mother-child relationship. 

PMID- 24278867
TI  - Sudden detraining deteriorates swimming training-induced enhancement of short
      term and spatial learning memories in mice.
AB  - In the present study, we investigated the effect of swimming training and sudden
      detraining on learning ability and spatial memory capability and on neurogenesis
      and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of
      mice. Male ICR mice were randomly assigned into three groups (n= 15 in each
      group): the control group, the swimming training group, and the detraining group.
      The mice in the swimming training group were made to swim (6 days/week, 60
      min/day) for 8 weeks. The mice in the detraining group were accomplished the same
      swimming program for 4 weeks and then discontinued exercise for 4 weeks. In the
      present results, enhanced short-term and spatial learning memories and increased
      hippocampal neurogenesis and BDNF expression were observed in the mice of the
      swimming training group. In contrast, decreased short-term and spatial learning
      memories were observed in the mice of the swimming detraining group compared to
      the control level. Hippocampal neurogenesis and BDNF expression were also
      decreased in the mice of the detraining group near to the control level. Here in
      this study, we suggest that sudden cessation of exercise training might bring
      decline of the brain functions. 

PMID- 24278868
TI  - Effects of Ylang-Ylang aroma on blood pressure and heart rate in healthy men.
AB  - Although the Ylang-Ylang aroma (YYA) has used as a general method for enhancing
      sedative effect, there was a little report on the efficacy of YYA on heart
      function using the electrocardiogram (EKG). Therefore, identifying of the effects
      of YYA on blood pressure (BP) and heart rate (HR) is important in order to
      demonstrate the effectiveness of YYA. The aim of this study was to investigate
      the effects of YYA on BP and HR in healthy men. Twenty-nine men took part in this
      study. The subjects were randomly divided into 2 groups: Ylang-Ylang group (YYG,
      n= 15) and control group (CG, n= 14). Physiological parameters recorded were BP
      by using a sphygmomanometer and HR by using an EKG. The present results
      demonstrated that inhalation of YYA significantly decreased the systolic and
      diastolic blood pressure. Inhalation of YYA also significantly decreased the HRs
      in 10 leads, except in lead I and aVR. This indicates that the HRs recorded in
      lead I and aVR were less sensitive or obtuse compared to those in the 10 other
      leads. Therefore, such a result reveals that it is necessary to be aware of the
      terms regarding the position. In the present results, YYA caused a reduction of
      HR and BP, and a relief of the arousal level in healthy men. The present results
      show a sedative effect of YYA, and this study provides some evidences for the
      usage of YYA in medicinal agent. 

PMID- 24278869
TI  - Regular exercise modulates obesity factors and body composition in sturdy men.
AB  - The purpose of this study was to find the change and correlation between obesity
      factors and body composition according to regular exercise. Thirty-six sturdy men
      at twenty years old in 'K' university students were participated in this study.
      The subjects were randomly divided into two groups (n= 18 in each group): control
      group and regular exercise group. Exercise program composed of three programs:
      warm-up (10 min), work-out (30-60 min), cool-down (10 min), and categorized by
      five days per week for eight weeks. Aerobic exercise using a treadmill at 60% of
      heart rate reserve was performed, and weight training was composed of nine
      different exercises for the large muscles. Before the performing regular
      exercise, there was no significant difference between control and regular
      exercise groups. In the present results, 8 weeks regular exercise significantly
      decreased leptin, weight, fat mass, % fat, waist to hip ratio (WHR), and body
      mass index (BMI) more than compared to before performing regular exercise,
      whereas significantly enhanced lean mass more than compared to before performing
      regular exercise. Furthermore, regular exercise group reduced leptin, weight, fat
      mass, % fat, WHR, and BMI compared to control group in the post test. In the
      correlation of obesity-related factors and body composition, tumor necrosis
      factor-alpha (TNF-alpha) showed correlation with weight, lean mass, and fat mass
      after performing regular exercise. Here in this study, we suggest that regular
      exercise is a valuable tool for the improvement of health in the sturdy men,
      because regular exercise suppresses body fat and obesity-related factors. 

PMID- 24278870
TI  - The relationship of baby boomers' participation motivation in leisure sports with
      recovery resilience and life satisfaction.
AB  - This study aimed to provide basic materials for resolving the problems of baby
      boomers, emerging as a social issue by identifying the effect of baby boomers'
      participation motivation in leisure sports activities on recovery resilience and
      life satisfaction empirically. Using the convenience sampling method, the
      subjects were conducted by baby boomer's 323 person lived in Seoul and Gyeong-in,
      2012, excluding the missing question paper of 27 person. For accomplishing this
      purpose of the study, the survey questionnaires were used to collect data.
      Collected data was processed by factor analysis, reliability analysis, multiple
      regression, SPSS for Win V 18.0 program. From the analysis of this study, the
      following conclusion were obtained: First, among participation motivation factors
      of baby boomers in leisure sports activities, psychological stability and health
      pursuit had a significant effect on all factors of recovery resilience, while
      among motivation of personal relationships had a significant effect on the sub
      factors of recovery resilience; empathy, optimism, and self-efficacy. Second,
      among participation motivation factors of baby boomers in leisure sports
      activities, psychological stability, personal relationships, and health pursuit
      had a significant effect on life satisfaction. 

PMID- 24278871
TI  - Effect of long-term resistance exercise on body composition, blood lipid factors,
      and vascular compliance in the hypertensive elderly men.
AB  - Hypertension is designated as either essential (primary) hypertension or
      secondary hypertension and is defined as a consistently elevated blood pressure
      exceeding 140/90 mmHg. Hypertension is called "the silent killer" because it
      often causes no symptoms for many years, even decades, until it finally damages
      certain critical organs. In various causes of hypertension, obesity is an
      increasing health problem worldwide, and several epidemiological studies have
      identified a positive association between obesity and an increased incidence of
      hypertension. Therefore, in the present study, we investigated the effect of long
      term resistance exercise on body composition, blood lipid profile, vascular
      compliance, and blood pressure in the elderly men. For this study, the In-Body
      test, blood lipid profile, and analysis of vascular compliance and blood pressure
      were performing before and after in experiment. The twenty male subjects aged
      between 68 and 72 yr were recruited from the 'Y' senior towers in Korea. All
      subjects performed exercises on a weight training machines 40 min once a day for
      52 weeks. The exercise intensity for resistance training was 60% of the 10 RM
      maximal voluntary contraction test. All subjects before performing resistance
      exercise showed an increase in hypertension following enhanced %fat, blood lipid
      factors (TC, LDL-C), whereas decreased lean body mass (LBM), vascular compliance.
      However, 52 weeks of resistance exercise suppressed %fat and LDL-C, whereas
      improved LBM, vascular compliance, resulting in reducing hypertensive levels in
      the elderly men. We suggest that resistance exercise can be a valuable tool for
      the remarkable improvement of hypertension. 

PMID- 24278872
TI  - The effects of empowered motivation on exercise adherence and physical fitness in
      college women.
AB  - The purpose of this study is to identify the effects of exercise adherence when
      exercise motivation was empowered. It was planned as a pretest-posttest
      nonequivalent quasi-experimental design. The study subjects were female college
      students who wanted exercise and agreed to participate in the Jane Fonda Workout
      Program (1982) for a period of six months. The subject sample was divided into an
      experimental group and a control group by college department to prevent
      contamination of the intervention, which promotes long-term exercise-program
      adherence through the EMPOWER Step Program. All subjects' body composition and
      physical fitness were measured using the Inbody (520) Body Composition Analyzer
      and Helmas (Korea) measuring equipment. Cronbach's alpha, t-test, odds ratio and
      analysis of covariance were used to analyze the data using the Statistical
      Package for the Social Sciences program. According to the results the
      experimental group showed a 66.66% exercise adherence success rate and the
      control group showed only a 26.31% success rate (OR= 5.60, P= 0.01; t= 2.932, P=
      0.006). Skeletal muscle mass was significantly higher in the experimental group
      than in the control group (F= 8.45, P= 0.006). Body fat mass decreased
      significantly more in the experimental group than in the control group (F= 6.08
      P= 0.01). Empowered motivation has positive effects on adherence to exercise
      regimes and physical fitness in female college students. Therefore it is
      suggested to actively utilize the EMPOWER Step Program to foster long-term
      exercise. 

PMID- 24278873
TI  - The effects of abdominal draw-in maneuver and core exercise on abdominal muscle
      thickness and Oswestry disability index in subjects with chronic low back pain.
AB  - The purpose of this study was to effects of abdominal draw-in maneuver and core
      exercise with 4 weeks using the musculoskeletal ultrasonography on muscle
      thickness and disability in subjects with low back pain. Twenty patients with
      nonspecific back pain (abdominal draw-in maneuver group: n= 10, core exercise
      group: n= 10) were recruited in the study. Both group received exercise
      intervention 3 times a week for 4weeks. The test were based on muscle thickness
      (transversus abdominis; Tra, internal oblique; IO and external oblique; EO),
      disability (Oswestry disability index; ODI) measured immediately before and after
      intervention. The data was measured by SPSS program 12.0 version and analyzed by
      Paired t-test and Independent t-test. The following results were obtained. The
      thickness of IO, EO for both group significantly improved except for muscle
      thickness of Tra. The ODI were significant difference for both groups. As the
      results of this study, we suggest that it may be effective method to apply to
      increase for the thickness of Tra, EO using abdominal draw-in maneuver and
      thickness of IO using core exercise. 

PMID- 24278874
TI  - The effects of ankle mobilization and active stretching on the difference of
      weight-bearing distribution, low back pain and flexibility in pronated-foots
      subjects.
AB  - The purpose of this study was designed to analyze the effects mobilization and
      active stretching on the difference of weight-bearing distribution, low back
      pain, and flexibility in pronated-foot subjects. The subjects of this study were
      16 chronic low back pain patients. They were randomly divided into the control
      and experimental group. The experimental group had used the model of ankle
      mobilization and calf muscle active stretching three times per week, for 4 weeks.
      The control group did same method without an ankle mobilization. The range of
      flexion and extension motion of the lumbar vertebrae and low back pain degree and
      difference of weight-bearing were measured before and after the experiment. The
      model of ankle mobilization and calf muscle stretching of pronated-foot
      significantly improved the range of flexion and extension motion of the
      vertebrae. And the visual analogue scale and distribution of weight-bearing were
      decreased in both of two groups. In other word, the exercise of this study showed
      that the model of ankle mobilization and calf muscle stretching of pronated-foot
      had positive effects on improving the range of flexion and extension motion of
      the vertebrae. The calf muscle stretching was easy and it is effective in therapy
      that patients by themselves and helped to recover the balance of the vertebrae to
      combine ankle mobilization and muscle stretching. 

PMID- 24278875
TI  - The effects of combined exercise intervention on body composition and physical
      fitness in elderly females at a nursing home.
AB  - The purpose of this study was to analyze the effects of practicable combined
      exercise program in daily lives on body composition and physical fitness in
      elderly females. A total of 34, old female adults and all over 75 yr of age
      participated in this study. Collected data were statistically analyzed by SPSS PC
      win 12.0/pc for by paired simple T-test. Alpha was set at .05. The results of the
      study showed statistical significance in weight (P< 0.001), body fat mass (P<
      0.001), waist-hip ratio (P< 0.001), basal metabolic rate (P< 0.05), body mass
      index (P< 0.001), standing-up and down on a chair (P< 0.001) and showed not
      statistically significant in one leg standing with eyes closed, back hand
      holding, grip strength and emotional state. But it was found that there was
      significant change in a mean value between pre and post test. 

PMID- 24278876
TI  - Lifeworld conflicts and relation rebirth of couple dancing sport participants.
AB  - This study aims to analyze how the conflict factors occur in lifeworld between
      couples are healed up through participating in the couple dancing sport, that is,
      how the couples are reborn to recover the relationship, and why they select the
      dancing sport for such an intermediate instrument. To achieve such research aims,
      a qualitative research has been conducted subjecting 5 couples, 10 people who
      both a couple is participating in the dancing sport activity. The results
      according to this research procedure are concluded in the following. First, the
      marital conflict factors occur in lifeworld include day-to-day factors, distance
      of conjugal relations, expression of negative emotion, etc. Second, the motives
      for selecting the dancing sport to resolve the marital conflict factors comprise
      of suggestions from surroundings, mass media, filling up the empty nest,
      proposals during consultation treatments, problem recognitions of conjugal
      relations, mutual agreement between a couple, etc. Third, the relation recovered
      through the couple dancing sport activity, i.e., the rebirth is deemed to be
      resulted from the promotion of communication opportunities through the couple
      dancing sport, formation of emotional communion between the couple, building new
      feelings between the couple, etc. 

PMID- 24278877
TI  - Complex exercise rehabilitation program for women of the II period of age with
      metabolic syndrome.
AB  - The purpose of this study was to develop a complex exercise program integrating
      Eastern and Western complex exercise rehabilitation programs in order to examine
      the effects of it on the human body with the subjects for women of the II period
      of mature age with metabolic syndrome. The subjects of this study are 60 II
      period of mature aged women with metabolic syndrome living in G City, and the
      experimental group conducted Taekwon-aerobic exercise, European rehabilitation
      gymnastics, gym ball exercise, and elastic band exercise while the control group
      performed European rehabilitation gymnastics, gym ball exercise, and elastic band
      exercise which is the rehabilitation program being presently conducted in Russia,
      for 90 min per day for three weeks. Two-way ANOVA with repeated measures was
      utilized to verify pre and post-intergroup difference, and the significant level
      was set as P< 0.05. Whereas body weight, % fat, WHR, SBP, DBP and blood glucose
      were significant decreased, muscle weight and pulse wave velocity were
      significant increased after complex exercise rehabilitation programs Both Eastern
      and Western complex exercise rehabilitation programs showed positive effects on
      the body of the II period of mature aged women with metabolic syndrome, and if
      various exercise programs are conducted, it will be more effective in improving
      II period of mature aged women's metabolic syndrome afterwards. 

PMID- 24278878
TI  - Effect of complex treatment using visual and auditory stimuli on the symptoms of
      attention deficit/hyperactivity disorder in children.
AB  - We investigated the effects of complex treatment using visual and auditory
      stimuli on the symptoms of attention deficit/hyperactivity disorder (ADHD) in
      children. Forty-seven male children (7-13 yr old), who were clinically diagnosed
      with ADHD at the Balance Brain Center in Seoul, Korea, were included in this
      study. The complex treatment consisted of visual and auditory stimuli, core
      muscle exercise, targeting ball exercise, ocular motor exercise, and visual motor
      integration. All subjects completed the complex treatment for 60 min/day, 2-3
      times/week for more than 12 weeks. Data regarding visual and auditory reaction
      time and cognitive function were obtained using the Neurosync program, Stroop
      Color-Word Test, and test of nonverbal intelligence (TONI) at pre- and post
      treatment. The complex treatment significantly decreased the total reaction time,
      while it increased the number of combo actions on visual and auditory stimuli (P<
      0.05). The Stroop color, word, and color-word scores were significantly increased
      at post-treatment compared to the scores at pretreatment (P< 0.05). There was no
      significant change in the TONI scores, although a tendency toward an increase in
      these scores was observed. In conclusion, complex treatment using visual and
      auditory stimuli alleviated the symptoms of ADHD and improved cognitive function
      in children. In addition, visual and auditory function might be possible
      indicators for demonstrating effective ADHD intervention. 

PMID- 24278879
TI  - The effect of McConnell taping on vastus medialis and lateralis activity during
      squatting in adults with patellofemoral pain syndrome.
AB  - This study aims to examine the effect of McConnell taping to patients with
      patellofemoral pain syndrome on the change of the muscle activity of vastus
      medialis and vastus lateralis during squatting. The total numbers of participants
      are 16 patients with pain in their knee. There are three different experiments:
      no-taping, placebo taping, and McConnell taping. As a result, both the muscle
      activity of vastus medialis and muscle activity ratio of vastus medialis to
      vastus lateralis increased in placebo taping compared to no-taping, which wasn't
      statistically significant. However, the muscle activity of vastus medialis and
      muscle activity ratio of vastus medialis to vastus lateralis increased in
      McConnell taping compared to no-taping, which was statistically significant.
      These results suggest that McConnell taping affects the activity of quadriceps by
      changing the position of the patella, and thus can effectively be applied in the
      treatment of patellofemoral pain syndrome. 

PMID- 24278880
TI  - The effect of convalescent meridian acupressure after exercise on stress hormones
      and lactic acid concentration changes.
AB  - Meridian acupressure has been used as the one way recovering body conditions. The
      purpose of this study was to investigate whether meridian acupressure is
      effective on removing cortisol, norepinephrine, epinephrine, and lactic acid in
      blood following exercise. The subjects were 12 healthy male college students and
      data were processed using SPSS 12.0 statistical program and the results were
      calculated by setting the significance level at P< 0.05. First, there was a
      significant difference between exercise recovery group except for stability group
      and acupressure recovery group in convalescent cortisol concentration changes
      after exercise (P= 0.001). And acupressure recovery group showed a significant
      difference compared with two groups (P= 0.001). Second, exercise recovery group
      showed nonsignificant difference in convalescent norepinephrine concentration
      changes but meridian acupressure recovery group showed a significant difference
      (P= 0.001). There was a significance difference in the groups rather than
      exercise recovery group and rest recovery group (P= 0.001). Third, exercise
      recovery group and acupressure recovery group showed a significant difference in
      convalescent epinephrine concentration changes after exercise (P= 0.001).
      However, rest recovery group showed nonsignificant difference. In addition, three
      groups showed nonsignificant difference in the groups. However, it showed in
      order of acupressure= exercise> rest recovery. Fourth, three groups showed a
      significant difference in convalescent lactic acid concentration changes after
      exercise (P = 0.001). And it showed in order of acupressure= exercise> rest
      recovery after recovery treatment in the groups (P= 0.001). 

PMID- 24278881
TI  - The increasing role of exercise rehabilitation.

PMID- 24278882
TI  - Aging, exercise, and extracellular matrix in the heart.
AB  - Aging is characterized by a progressive impairment of (a) cardiac structure
      including fibrosis and cardiomyocyte density, and (b) cardiac function including
      stroke volume, ejection fraction, and cardiac output. The cardiac remodeling
      involves loss of cardiac myocytes, reactive hypertrophy of the remaining cells,
      and increased extracellular matrix (ECM) and fibrosis in the aging heart,
      especially left ventricles. Fibrosis (i.e., accumulation of collagen) with aging
      is very critical in impairing cardiac function associated with increased
      myocardial stiffness. The balance of ECM remodeling via ECM synthesis and
      degradation is essential for normal cardiac structure and function. Thus an
      understanding of upstream ECM regulatory factors such as matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), tumor
      necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta),
      and myofibroblasts is necessary for gaining new insights into managing cardiac
      remodeling and dysfunction with aging. In contrast, exercise training effectively
      improves cardiac function in both young and older individuals. Exercise training
      also improves maximal cardiovascular function by increasing stroke volume and
      cardiac output. However, limited data indicate that exercise training might
      attenuate collagen content and remodeling in the aging heart. We recently found
      that 12 weeks of exercise training protected against geometric changes of
      collagen ECM in the aging heart and ameliorated age-associated dysregulation of
      ECM in the heart, as indicated by up-regulation of active MMPs as well as down
      regulation of TIMPs and TGF-beta. This review will provide a summary and
      discussion of aging and exercise effects on fibrosis and upstream regulators of
      ECM in the heart. 

PMID- 24278883
TI  - Treadmill exercise inhibits apoptotic neuronal cell death with suppressed
      vascular endothelial growth factor expression in the retinas of the diabetic
      rats.
AB  - Diabetic retinopathy is one of the most important microvascular complications in
      diabetes, and it is the major cause of visual loss. Physical exercise is known to
      ameliorate the symptoms of metabolic syndromes such as diabetic mellitus. In the
      present study, we investigated the effects of treadmill exercise on vascular
      endothelial growth factor (VEGF) expression and apoptotic cell death in the
      retinas of streptozotocin (STZ)-induced diabetic rats. The male Sprague-Dawley
      rats were randomly divided into three groups (n = 10 in each group): control
      group, STZ-induce diabetes group, STZ-induced diabetes and treadmill exercise
      group. To induce diabetes in the experimental animals, a single intraperitioneal
      injection of STZ (50 mg/kg) was given to each animal. The rats in the exercise
      group were forced to run on a motorized treadmill for 30 min once a day during 1
      week starting 6 weeks after STZ injection. In the present results, VEGF
      expression in the retinas was increased by induction of diabetes. The numbers of
      caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL)-positive cells in the retinas were also enhanced by
      induction of diabetes. Treadmill exercise significantly decreased VEGF expression
      and suppressed the number of TUNEL-positive and caspase-3-positive cells in the
      retinas of diabetic rats. In the present study, we have shown that treadmill
      exercise might alleviate the progression of diabetic retinopathy through
      suppressing VEGF expression and apoptotic cell death in the retinas of the
      diabetic rats. 

PMID- 24278884
TI  - Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine
      induced Parkinson's rats.
AB  - Progressive loss of dopaminergic neurons in substantia nigra is a key
      pathogenesis of Parkinson's disease. In the present study, we investigated the
      effects of treadmill exercise on short-term memory, apoptotic dopaminergic
      neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation
      in the hippocampal dentate gyrus of Parkinson's rats. Parkinson's rats were made
      by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic
      instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection
      group exhibited significant rotational asymmetry following apomorphine challenge.
      The rats in the exercise groups were put on the treadmill to run for 30 min once
      a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the
      present results, extensive degeneration of the dopaminergic neurons in the
      substantia nigra with loss of dopaminergic fibers in the striatum were produced
      in the rats without treadmill running, which resulted in short-term memory
      impairment. However, the rats performing treadmill running for 2 weeks alleviated
      nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment
      with increasing cell proliferation in the hippocampal dentate gyrus of
      Parkinson's rats. The present results show that treadmill exercise may provide
      therapeutic value for the Parkinson's disease. 

PMID- 24278885
TI  - The effects of core stability strength exercise on muscle activity and trunk
      impairment scale in stroke patients.
AB  - The purpose of this study was to examine the effects of core stability-enhancing
      exercises on the lower trunk and muscle activity of stroke patients. The control
      group (n = 10) underwent standard exercise therapy, while the experiment group (n
      =10) underwent both the core stability-enhancing exercise and standard exercise
      therapy simultaneously. The standard exercise therapy applied to the two groups
      included weight bearing and weight shifts and joint movements to improve
      flexibility and the range of motion. The core stability-enhancing exercise was
      performed 5 times a week for 30 min over a period of 4 weeks in the room where
      the patients were treated. For all 20 subject, the items measured before the
      exercise were measured after the therapeutic intervention, and changes in muscle
      activity of the lower trunk were evaluated. The activity and stability of the
      core muscles were measured using surface electromyography and the trunk
      impairment scale (TIS). The mean TIS score and muscle activity of the lower trunk
      increased in the experiment group significantly after performing the core
      stability-enhancing exercise (P<0.05). The results of this study show that the
      core stability-enhancing exercise is effective in improving muscle activity of
      the lower trunk, which is affected by hemiplegia. 

PMID- 24278886
TI  - Relationships between lower limb muscle architecture and activities and
      participation of children with cerebral palsy.
AB  - The purpose of this study was to determine the effects of the structure of
      skeletal muscle of lower extremities on function, activity, and participation of
      children with cerebral palsy. The subjects were 38 hospitalized patients and 13
      infants with normal development. The following clinical measures were used for
      assessment of activity daily living and functional level of gross motor: Gross
      Motor Function Classification System (GMFCS), Gross Motor Function Measure
      (GMFM), Wee Functional Independence Measure (WeeFIM), International
      Classification of Functioning Child and Youth (ICF CY). Muscle thickness and
      strength of knee extensor and ankle extensor were collected using ultrasonography
      and manual muscle tester. Following the results of ICF CY evaluation for body
      function, activity, learning and application of knowledge, communication and
      environmental factors showed a decline (P< 0.05). Significant differences in the
      thickness of muscle was observed according to the GMFCS level, thickness of knee
      extensor and ankle extensor of cerebral palsy (P< 0.05), and clauses of self
      care, activity, mobility, ambulation, communication, and social acknowledgement
      (P< 0.05). Following analysis, results showed negative correlation in the
      thickness of muscle, muscle strength, major motor function, daily activity and
      participation; the score of ICF-CY was shown to decline due to the high score for
      differences in thickness of muscle, muscle strength, WeeFIM, and GMFM. The
      thickness and muscle strength of lower extremities affect main functions of the
      body and improvement of muscle strength of lower extremities may have positive
      effects on social standards such as activity and participation of cerebral palsy.

PMID- 24278887
TI  - Characteristics of upper limb muscular strength in male wheelchair tennis
      players.
AB  - The purpose of this study was to identify the characteristics of muscular
      strength in upper limb and to present the preliminary information for development
      of sports injury prevention program and exercise rehabilitation program in
      wheelchair tennis players. Participants were 12 male wheelchair tennis players.
      Muscular strength was measured in shoulder and elbow joints with isokinetic
      dynamometer. Ipsilateral (IR) and bilateral (BR) balance ratio were calculated
      with isokinetic strength at 60 degrees /sec. As a result, extension strength (ES)
      was significantly higher than flexion strength (FS) (P< 0.001), and IR in both
      sides and BR in ES were maintained within normal range whereas BR in FS was lower
      than normal range in shoulder joint. In elbow joint FS was significantly higher
      than ES (P< 0.05), and IR and BR were lower than normal range. Consequently, the
      different tendency in IR between shoulder and elbow joints and lower IR and BR in
      elbow joints could be the characteristics in male wheelchair tennis players. It
      is suggested that flexor strengthening program in nondominant shoulder joint,
      extensor strengthening program in both elbow joint, and flexor strengthening
      program in non-dominant elbow joint should be introduced for male wheelchair
      tennis players. 

PMID- 24278888
TI  - The effects of health perception on living health belief, living satisfaction and
      wellbeing-oriented activities according to swimming participation with middle
      aged women.
AB  - This study aims to examine the effects of health perception on health belief,
      life satisfaction, and wellbeing-oriented activities according to swimming
      participation with middle-aged women. First, the subvariables of health
      perception, health interest and health concern, did exert significant effects on
      the subvariables of health belief, perceived benefit and perceived disability.
      Health interest and health concern also showed significant effects on the
      subvariables of life satisfaction and wellbeing-oriented activities, exercise
      orientation and hobby orientation, as well. Second, the subvariables of health
      perception, resistance and sensitivity, indicated significant effects on the
      subvariable of health belief, perceived disability, and they also showed
      significant effects on life satisfaction, too. Also, resistance-sensitivity had
      significant effects on the subvariables of wellbeing-oriented activities, mental
      health orientation and hobby orientation, too. 

PMID- 24278889
TI  - Tuberculosis of testis and prostate that mimicked testicular cancer in young male
      soccer player.
AB  - Staphylococcus infection was the most common organism found in infection of
      athletics, and tuberculosis (TB) was rare. Although genitourinary tuberculosis
      (GUTB) was the most common subtype of extrapulmonary tuberculosis (EPTB) in the
      past, it was recently reported to account for less than 0.5% of all patients with
      EPTB and 1.5% of all patients with pulmonary tuberculosis (TB). And, there are
      few cases reported about concomitant tuberculous infection of testis and
      prostate. Pubic pain is a common symptom in soccer player and its cause can be
      difficult to determine. A 25-yr-old male soccer player presented with persistent
      pubic pain of unknown origin. Incidentally, right testicular mass was detected on
      physical examination. Computed tomography revealed a multiple enlarged
      retroperitoneal lymph nodes. Under the clinical diagnosis of a right testicular
      tumor, right radical inguinal orchiectomy was performed. And prostate biopsy was
      performed due to elevated serum prostate specific antigen (PSA). Pathologic
      examination confirmed concomitant TB of testis and prostate. 

PMID- 24278890
TI  - Exercise rehabilitation, work to revive the human becoming the driving force of
      the country.

PMID- 24278891
TI  - Neuropathic pain in hereditary peripheral neuropathy.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory
      neuropathy. Previous studies have shown that neuropathic pain is an occasional
      symptom of CMT referred by CMT patients. However, neuropathic pain is not
      considered a significant symptom in CMT patient and no researchers have studied
      profoundly the pathophysiology of neuropathic pain in CMT. Here, we highlight the
      relationship between CMT disease and neuropathic pain via previous several
      studies. 

PMID- 24278892
TI  - Clinical evaluation of upper limb function: Patient's impairment, disability and
      health-related quality of life.
AB  - Musculoskeletal disorders substantially impacts physical activity, mental state,
      and quality of life (QOL). Generally, comprehensive assessment of upper limb
      function requires measures of impairment or disability as well as health-related
      quality of life. A growing number of outcome instrument have been introduced to
      evaluate upper limb function and disability, and these measures can be
      categorized as patient- or clinician-based, and as condition specific or general
      health-related QOL evaluations. The upper limb outcome instruments reviewed in
      this article assess different aspect of upper limb conditions, and the measures
      are affected by differences in cultural, psychological, and gender aspect of
      illness perception and behavior. Therefore, physician should select/interpret the
      outcome instruments addressing their primary purpose of research. Information
      about regional instruments for upper limb condition and health-related QOL in
      upper limb disorder may help us in decision-making for treatment priority or in
      interpretation of the treatment outcomes. 

PMID- 24278893
TI  - Treadmill exercise ameliorates impairment of spatial learning ability through
      enhancing dopamine expression in hypoxic ischemia brain injury in neonatal rats.
AB  - Substantia nigra and striatum are vulnerable to hypoxic ischemia brain injury.
      Physical exercise promotes cell survival and functional recovery after brain
      injury. However, the effects of treadmill exercise on nigro-striatal dopaminergic
      neuronal loss induced by hypoxic ischemia brain injury in neonatal stage are
      largely unknown. We determined the effects of treadmill exercise on survival of
      dopamine neurons in the substantia nigra and dopaminergic fibers in the striatum
      after hypoxic ischemia brain injury. On postnatal 7 day, left common carotid
      artery of the neonatal rats ligated for two hours and the neonatal rats were
      exposed to hypoxia conditions for one hour. The rat pups in the exercise groups
      were forced to run on a motorized treadmill for 30 min once a day for 12 weeks,
      starting 22 days after induction of hypoxic ischemia brain injury. Spatial
      learning ability in rat pups was determined by Morris water maze test after last
      treadmill exercise. The viability of dopamine neurons in the substantia nigra and
      dopamine fibers in the striatum were analyzed using immunohistochemistry. In this
      study, hypoxic ischemia injury caused loss of dopamine neurons in the substantia
      nigra and dopaminergic fibers in the striatum. Induction of hypoxic ischemia
      deteriorated spatial learning ability. Treadmill exercise ameliorated nigro
      striatal dopaminergic neuronal loss, resulting in the improvement of spatial
      learning ability. The present study suggests the possibility that treadmill
      exercise in early adolescent period may provide a useful strategy for the
      recovery after neonatal hypoxic ischemia brain injury. 

PMID- 24278894
TI  - Treadmill exercise alleviates post-traumatic stress disorder-induced impairment
      of spatial learning memory in rats.
AB  - Post-traumatic stress disorder (PTSD) is a condition which occurs after a person
      has experienced unusual stress. The neurons in the hippocampus are especially
      vulnerable to the PTSD. In the present study, the effect of treadmill exercise on
      spatial learning memory and cell proliferation in the hippocampus of rats with
      PTSD. Radial 8-arm maze test and immunohistochemistr for 5-bromo-2'-deoxyridine
      (BrdU) and double-cortin (DCX) were conducted for this experiment. For the
      inducing PTSD, the rats were exposure to 0.2 mA electric foot shock for 7
      consecutive days. Electric foot shock continued 6 seconds, repeated 10 times with
      a 30 sec interval per one trial, and repeated 3 trials per day. The rats in the
      exercise groups were forced to run on a motorized treadmill for 30 min once a day
      for 4 weeks, stating one day after finishing last electric food shock. Presently,
      the PTSD rats showed longer time of successful performance, higher error number,
      and lower correct number in the radial-8-arm maze test. Cell proliferation and
      DCX expression in the hippocampal dentate gyrus were suppressed in the PTSD rats.
      In contrast, treadmill exercise alleviated PTSD-induced impairment of spatial
      learning memory. The rats performed treadmill exercise showed longer time of
      successful performance, higher error number, and lower correct number in the
      radial-8-arm maze test. Treadmill exercise also enhanced cell proliferation and
      DCX expression in the hippocampal dentate gyrus of PTSD rats. The present study
      demonstrated that treadmill exercise ameliorated PTSD-induced memory impairment
      through enhancing cell proliferation in the hippocampus. 

PMID- 24278895
TI  - Finger exercise with keyboard playing in adults with cerebral palsy: A
      preliminary study.
AB  - The purpose of this study is to examine the effects of Therapeutic Instrument
      Music Performance (TIMP) for fine motor exercises in adults with cerebral palsy
      (CP). Individuals with CP (n = 5) received a total of twelve, 30-min TIMP
      sessions, two days per week for six to nine weeks. Pre- and post-Music Instrument
      Digital Interface (MIDI) data were used as a measure of hand function. Pre
      velocity was significantly different from the normative data obtained from
      typical adults (n = 20); however, post-velocity did not yield significance,
      specifically in the second and fifth fingers, indicating improvement in hand
      function for the adults with cerebral palsy. The finding implies that TIMP using
      keyboard playing may effectively improve manual dexterity and velocity of finger
      movement. Based on these results, future program development of instrumental
      playing for adults with CP is called for to enhance both their independent living
      skills and quality of life. 

PMID- 24278896
TI  - Empirical application of empathy enhancing program based on movement concept for
      married couples in conflict.
AB  - In the field of marital therapy, it is known that couple movement program helps
      married couples faced with conflict situation to rebuild the relationship and to
      maintain a family homeostasis. The purpose of this study was to configure and
      apply the kinesthetic empathy program and to assess the effectiveness for married
      couples in conflict. To achieve the research aims, qualitative research method
      has been conducted, subjecting three couples, 6 people, who are participating in
      expressive movement program for this study. The study used focus group interview
      method for collecting date and employed for the interview method by mixing the
      semi-structured and unstructured questionnaire. The results were followings.
      First, through kinesthetic empathy enhancing program, one could develop self
      awareness and emotional attunement. Second, the result showed the relationship
      between intention and empathy. It shows that "knowing spouse's hidden intention"
      is significant factors to understand others. Third, kinesthetic empathy program
      could complement general marriage counseling program. The results of this study
      provide empirical evidence that movement program functions as an empathy enhancer
      through the process of perceiving, feeling, thinking, and interacting with
      others. 

PMID- 24278897
TI  - The effects of psychological variables of father's role on parenting
      participation.
AB  - The purpose of this study is to examine how father's psychological variable of
      role awareness affects parenting participation. Data were collected by the survey
      in fathers of 363 children in public kindergartens and national/public and
      private nurseries and analyzed by using multiple regression analysis. The results
      showed that fathers perceiving their role of educating (for cognitive
      development, social skills, and physical health) and of meeting the needs (needs
      for health protection, and emotional needs) participated actively in parenting
      and that those perceiving their role of meeting the needs for food, clothing, and
      shelter participated passively in parenting. On the basis of these results,
      strategic and practical implications were given to induce fathers to participate
      more actively in parenting. 

PMID- 24278898
TI  - Analysis on leisure patterns of the pre-elderly adults.
AB  - The purpose of study is to analyze how leisure activities affect the near elders'
      preparation for successful and productive aging. To achieve the purpose of the
      study, this study was conducted in 2012 and the data was collected by using multi
      stage stratified cluster random sampling method in the great city area (6
      places), metropolitan area (7 places), medium-sized urban area (6 places), and
      rural area (6 places). Out of the total number of 1,000 copies of questionnaire
      distributed to pre-elders (Baby-boomers from 55 yr to 64 yr), 978 were collected
      and used for data analysis. According to the result, the more time, frequency and
      intensity in leisure and recreational participation, the higher the satisfaction
      level and the happiness level in their life. It means that leisure and
      recreational activities play an important role for their life. In other words,
      for pre-elders, leisure activities can be regarded as the important element for
      preparation of their old age. Therefore, the leisure and recreation for pre
      elderly adults should not be recognized as a tool for improving the economic
      productivity but for reinforcing the recovery resilience. 

PMID- 24278899
TI  - Erratum: Funding Acknowledgment in Journal of Exercise Rehabilitation (JER).

PMID- 24278900
TI  - Erratum: Figure Change in Journal of Exercise Rehabilitation (JER).
AB  - [This corrects the article on p. 354 in vol. 9.].

PMID- 24278901
TI  - A conversation with AAOS President, Joshua J. Jacobs, MD.

PMID- 24278902
TI  - 5 points on unicompartmental knee arthroplasty.

PMID- 24278903
TI  - Hip resurfacing arthroplasty in severely obese patients.
AB  - We conducted a study of outcomes of modern hip resurfacing arthroplasty (HRA) in
      severely obese patients. Patients who had undergone HRA and been followed for a
      minimum of 2 years were divided into 2 groups, those with body mass index under
      35 (control, 366 hips) and those with body mass index of 35 or above (study, 63
      hips). At mean follow-up of 41 months, there was no significant difference
      between the groups with respect to postoperative Harris Hip Scores, complication
      rates, and need for revision. Six revision surgeries were required in the control
      group (98.4% survival), and 2 were required in the study group (96.8% survival).
      These results suggest that severely obese patients should be considered
      candidates for HRA. 

PMID- 24278904
TI  - Synergistic effect of using a transcutaneous electrical joint stimulator and an
      unloading brace in treating osteoarthritis of the knee.
AB  - Medical treatments and less invasive surgical approaches for knee osteoarthritis
      are variably effective, and total knee arthroplasty (TKA) is generally reserved
      for the most severe cases. The care gap between more conservative treatments and
      TKA leaves many patients with unresolved pain and loss of function for long
      periods. We conducted a study to determine if incorporating the BioniCare
      stimulator into an unloading brace would produce more rapid improvement and
      result in increased adherence and efficacy. Two hundred eighty-nine patients
      treated only with BioniCare served as historical controls and were compared with
      225 patients treated with BioniCare combined with an unloading brace. Means and
      standard deviations of the changes in scores for pain intensity in the past 48
      hours, pain and associated symptoms, patient global assessment, pain on going up
      or down stairs, and pain on walking on a flat surface and the effect sizes at 1,
      3, 6, and 12 months, as well as the percentages of patients achieving at least
      20% improvement, and at least 50% improvement, demonstrated that treatment with
      stimulator and unloading brace combined was significantly superior to treatment
      with the stimulator alone. 

PMID- 24278905
TI  - Isolated vastus lateralis tendon avulsion.
AB  - Isolated avulsion of the vastus lateralis tendon is a very rare injury. To our
      knowledge, only 1 case has been reported in the literature. This tendon is
      crucial to knee stability and proper patellofemoral tracking. As isolated
      avulsion of the tendon tends to occur in young, active males, early surgical
      repair is recommended to allow them to maintain a high level of functional
      ability. We present the case of a 49-year-old man who sustained an isolated
      vastus lateralis tendon avulsion injury. The injury was successfully treated with
      suture anchor repair. 

PMID- 24278906
TI  - Missed rotator cuff tears in polytraumatized patients.
AB  - If not identified early, rotator cuff tears in polytraumatized patients can
      become debilitating. Traumatic rotator cuff tears are often massive, and
      generally retract over a short period of time. If a tear is missed or becomes
      irreparable, the consequences are profound, and can be devastating, especially to
      a younger, active person. In this article, we report 2 cases of initially
      untreated rotator cuff tears in polytraumatized patients and briefly review the
      literature. 

PMID- 24278907
TI  - Provisional mini-fragment plate fixation in clavicle shaft fractures.
AB  - Plate fixation has an increasingly prominent role in the management of select
      clavicle fractures. However, many fracture patterns are not easily reduced and
      provisionally stabilized with conventional clamp application and lag-screw
      placement, and maintaining an appropriate reduction can be a challenge. In this
      article, we present a technique in which a mini-fragment plate is used to
      provisionally maintain fracture reduction while the definitive plate is applied. 

PMID- 24278908
TI  - Dual-mobility acetabular components in total hip arthroplasty.
AB  - With dislocation being one of the most serious complications of total hip
      arthroplasty, prevention of recurrent instability has been the driving force
      behind several implant designs, including large-diameter heads, metal-on-metal
      bearing surfaces, and constrained acetabular components. Dual-articulation
      acetabular component design was similarly conceived in an effort to reduce
      postoperative dislocation risk. This design, developed in France in 1975 and
      popularized in Europe, was recently approved in the United States and represents
      a new surgical option for United States orthopedic surgeons performing total hip
      arthroplasty. In this article, we review the dual-articulation design in terms of
      its history, biomechanical concepts, published indications, contraindications,
      outcomes, and complications based on more than 20 years of largely French
      clinical experience. 

PMID- 24278909
TI  - Effect of a second joint arthroplasty on metal ion levels after primary total hip
      arthroplasty.
AB  - Serum metal ion levels increase after primary total hip arthroplasty (THA)
      regardless of bearing surface. We conducted a study to determine the effect of a
      second joint arthroplasty on existing serum metal ion levels at long-term
      followup. Twelve patients underwent primary THA and then either another THA (8
      patients) or total knee arthroplasty (TKA) (4 patients). The secondary procedures
      were performed a mean of 102.7 months (range, 36-144 months) after the index
      surgeries. The secondary THA group had significantly elevated levels of cobalt
      ion at 36 and 48 months, chromium ion at 12 and 24 months, and titanium ion at 48
      and 72 months. The TKA group had no significant differences in cobalt, chromium,
      or titanium ion levels up to 72 months after surgery. Overall, when metal
      polyethylene THA was performed after primary THA, there was a trend toward
      elevated serum metal ion levels at all follow-up intervals. This trend should be
      investigated with larger clinical trials. 

PMID- 24278910
TI  - Effect of preoperative hemoglobin A(1c) level on acute postoperative
      complications of total joint arthroplasty.
AB  - Diabetes mellitus is a well-established risk factor for postoperative
      complications of total joint arthroplasty (TJA). We conducted a study to identify
      a specific hemoglobin A1c (HbA1c) level at which immediate postoperative
      complication rates increased after TJA. HbA1c levels were measured within 90 days
      preoperatively. Complications were documented during the acute postoperative
      period. Charts were reviewed, and each patient was given a score based on how
      many of these postoperative complications occurred. Overall, 1118 patients were
      retrospectively analyzed between 2009 and 2011. Patients were grouped into 5
      HbA1c level ranges, and a mean postoperative complication point score was
      obtained for each group. We found that mean postoperative complication rates
      increased along with HbA1c levels; HbA1c levels higher than 7.5% correlate
      strongly with a higher rate of postoperative complications. These findings
      provide a good foundation for prospective studies and further evidence of the
      effects of HbA1c levels. If an adequate treatment plan for these patients
      emerges, these findings may help lower readmission rates as well. 

PMID- 24278911
TI  - Primary knee arthrodesis for severe crystalline arthropathy.
AB  - Gout is a common form of inflammatory arthritis involving deposition of
      monosodium urate crystals within a diarthroidal joint. In this article, we report
      the case of a 54-year-old man who had severe, uncontrolled gout and presented
      with a 10-year history of knee pain. On consideration of all patient factors,
      including age, desired functional level, significant bone loss, periarticular
      soft-tissue masses, significant ligamentous instability, and difficult access to
      health care, knee arthrodesis was the surgery of choice. A knee fusion for gouty
      arthritis allowed the patient to have a stable, pain-free knee. 

PMID- 24278912
TI  - Value, clinical outcomes, and perceptions of care.

PMID- 24278913
TI  - Internal bone temperature change during guided surgery preparations for dental
      implants: an in vitro study.
AB  - PURPOSE: The aim of this pig model study was to verify whether the use of devices
      (surgical templates) or procedures (flapless or flap) of guided surgery may cause
      a potentially pathologic increase of temperature during the bone preparation.
      MATERIALS AND METHODS: In this in vitro study, pig ribs with mean cortical
      thickness of 1.90 mm were used. Open-flap and flapless guided surgery
      (experimental groups OGS and FGS) and open-flap and flapless conventional
      technique (control groups OSS and OFS) were performed. Temperature changes were
      recorded at a distance of 0.5 mm from the final test osteotomy by 2 thermocouples
      at depths of 1.5 (point A) and 12 mm (point B). Data were collected from 80
      measurements, 10 for each group. RESULTS: A statistically significant increase of
      temperature was reported for the FGS and OGS groups considering the measurement
      at point A (mean Deltat 4.81 degrees and 4.21 degrees, respectively). The
      measurement at Point B for the FGS group compared to the FSS group did not differ
      significantly for the 3-mm drill, nor did the OSS group with the 2-mm drill.
      CONCLUSIONS: Site preparation with surgical stents generated higher bone
      temperature than conventional drilling. However, this heat generation did not
      reach temperature levels dangerous for the bone.

PMID- 24278914
TI  - Long-term outcome of one-piece implants. Part II: Prosthetic outcomes. A
      systematic literature review with meta-analysis.
AB  - PURPOSE: To evaluate the long-term clinical performance of prosthetic
      reconstructions on one-piece implants, with a focus on technical and biological
      complications. MATERIALS AND METHODS: An electronic MEDLINE search complemented
      by a manual search was conducted to identify randomized and prospective
      controlled clinical trials on one-piece implants. Additional inclusion criteria
      were a mean follow-up period of at least 5 years and an inception cohort where
      more than 80% of the enrolled patients remained in the study at the 5- or 10-year
      observation point. RESULTS: Sixty-six studies from an initial yield of 597 titles
      were selected, and the data were extracted. Of the full-text articles examined,
      46 were excluded and a total of 20 articles were finally selected. All studies
      were published between 1995 and 2011. Two different study designs were
      identified: 4 randomized controlled trials and 16 prospective cohort studies. The
      studies were analyzed and classified according to study type, patient
      characteristics, prosthetic characteristics, and biologic and technical
      complications after 5 and 10 years. The meta-analysis of the included studies
      showed a prosthetic survival rate for one-piece, one-part implants of 82.81%
      after 5 years and 97.85% and 98.24% in two-part implants after 5 and 10 years,
      respectively. Although the prosthetic survival rates were high, complications
      were frequent: complications of the suprastructure (18.44% to 18.75%), screw
      loosening/fracture (7.64%), soft-tissue complications (4.69% to 8.25%), sensory
      disturbances (0.36% to 6.25%), implant loss before loading (0% to 0.23%) and
      during function (1.10% to 3.21%), and implant fracture (0.0004%). CONCLUSION:
      Within the limits of this systematic review, it can be concluded that despite
      high long-term prosthetic survival rates, technical and biologic complications
      are frequent in one-piece implants, both in one-part and two-part designs.
      Further randomized clinical trials are needed to provide more information about
      the outcome of different variables associated with this type of implant design.

PMID- 24278915
TI  - The effect of subgingival ozone and/or hydrogen peroxide on the development of
      peri-implant mucositis: a double-blind randomized controlled trial.
AB  - PURPOSE: This double-blind randomized controlled trial assessed the effect of
      subgingival ozone (O3, gaseous ozone, HealOzone MK II, KaVo) and/or hydrogen
      peroxide (H2O2) on the development of peri-implant mucositis. MATERIALS AND
      METHODS: Twenty subjects (mean age, 60 +/- 7.7 years) with 80 implants (4
      implants each) were recruited. First, a 2-week pretrial phase took place to
      achieve healthy gingiva. Subsequently, partial gum shields were constructed for
      the experimental area (around the 4 implants); subjects were asked to refrain
      from brushing in that area by wearing the gum shield. The following treatments
      were randomly applied (for 60 seconds) to implant sites on days 0, 7, and 14: (1)
      air (O2) and saline (0.9% NaCl) (control group), (2) O2 and H2O2 (3%), (3) O3 and
      saline, and (4) O3 and H2O2. Plaque, gingival, and bleeding indices were recorded
      on days 0, 7, 14, and 21. RESULTS: Significant differences were seen among the
      treatments (P < .01) in plaque (F = 16.68), modified gingival (F = 7.86), and
      bleeding (F = 18.42) indices. O3 + saline and O3 + H2O2 produced optimum gingival
      health scores and were equally effective and the most effective in controlling
      bleeding (mean score = 0.05), while O2 + saline was the least effective (mean
      score = 0.56). CONCLUSION: Ozone showed great potential for management of peri
      implant mucositis.

PMID- 24278916
TI  - Additive manufacturing technology (direct metal laser sintering) as a novel
      approach to fabricate functionally graded titanium implants: preliminary
      investigation of fabrication parameters.
AB  - PURPOSE: This article describes the preliminary findings of the mechanical
      properties of functionally graded titanium with controlled distribution of
      porosity and a reduced Young's modulus on the basis of a computeraided design
      (CAD) file, using the rapid-prototyping, direct metal laser sintering (DMLS)
      technique. MATERIALS AND METHODS: Sixty specimens of Ti-6Al-4V were created using
      a DMLS machine (M270) following the standard for tensile testing of metals. One
      group was fabricated with only 170 W of laser energy to create fully dense
      specimens (control group). The remaining specimens all featured an outer fully
      dense "skin" layer and a partially sintered porous inner "core" region. The outer
      "skin" of each specimen was scanned at 170 W and set at a thickness of 0.35,
      1.00, or 1.50 mm for different specimen groups. The inner "core" of each specimen
      was scanned at a lower laser power (43 or 85 W). RESULTS: The partially sintered
      core was clearly visible in all specimens, with somewhat greater porosity with
      the lower laser power. However, the amount of porosity in the core region was not
      related to the laser power alone; thinner skin layers resulted in higher porosity
      for the same power values in the core structure. The lowest Young's modulus
      achieved, 35 GPa, is close to that of bone and was achieved with a laser power of
      43 W and a skin thickness of 0.35 mm, producing a core that comprised 74% of the
      total volume. CONCLUSION: Additive manufacturing technology may provide an
      efficient alternative way to fabricate customized dental implants based on a CAD
      file with a functionally graded structure that may minimize stress shielding and
      improve the long-term performance of dental implants.

PMID- 24278917
TI  - Essential oils and zirconia dental implant materials.
AB  - PURPOSE: This study was conducted to evaluate the effectiveness of natural
      antimicrobial agents in reducing biofilm development on different titanium and
      zirconia dental implant materials in vitro using a constant depth film fermentor
      (CDFF). MATERIALS AND METHODS: Contact angles and surface free energy were
      determined for all surfaces. Biofilms were grown on disks of polished partially
      stabilized zirconia, titanium blasted with zirconia, titanium blasted with
      zirconia and acid-etched, and polished titanium using a CDFF to simulate oral
      cavity conditions. Antimicrobials (cinnamon oil, clove oil, chlorhexidine
      gluconate, or 0.5% Tween 80) were pulsed twice daily to the biofilm to mimic
      application in the oral cavity. Samples were taken after 6, 24, and 48 hours.
      Serial dilutions were made and plated onto agar. Bacterial colonies were counted
      to determine colony-forming units/mL. RESULTS: Treatment of different implant
      material surfaces with the various antimicrobial agents led to significant
      increases in wettability and free energy on all surfaces. All surfaces showed a
      remarkable decrease in bacterial adhesion in the first 2 days in a relatively
      similar manner, with significant reduction in most of them, particularly after 48
      hours. CONCLUSIONS: Functionalization of different dental implant material
      surfaces with essential oils resulted in immediate and ongoing antibacterial and
      antiplaque activities, and this antibacterial effect was enhanced with increased
      plaque age. Differences in the type of material seemed to have little effect on
      bacterial adhesion after treatment with antimicrobial agents. Expansion of this
      work with in vivo studies and clinical trials would be valuable.

PMID- 24278918
TI  - Osseointegration of oral implants after delayed placement in rabbits: a
      microcomputed tomography and histomorphometric study.
AB  - PURPOSE: This study compared osseointegration of implants placed 14 days after
      implant site preparation with that of immediately placed implants in rabbit
      femurs. MATERIALS AND METHODS: Implants were placed bilaterally in the femoral
      condyles of 12 rabbits. On one side, the implants were placed 14 days after
      osteotomy, and the other side received implants immediately after osteotomy.
      Healing was assessed by microcomputed tomography and histomorphometry. RESULTS:
      The delayed implants (placed 14 days after osteotomy) showed better
      osseointegration than the immediately placed implants. Bone-to-implant contact
      and bone volume, as assessed by histomorphometry and microcomputed tomography,
      were significantly higher for the implants placed after 14 days. CONCLUSIONS:
      From this study, it can be concluded that early osteotomy bed preparation and
      placement of implants after a 2-week delay predisposes to better bone-implant
      interface healing.

PMID- 24278919
TI  - Evaluation of accuracy of complete-arch multiple-unit abutment-level dental
      implant impressions using different impression and splinting materials.
AB  - PURPOSE: This in vitro study evaluated the accuracy of multiple-unit dental
      implant casts obtained from splinted or nonsplinted direct impression techniques
      using various splinting materials by comparing the casts to the reference models.
      The effect of two different impression materials on the accuracy of the implant
      casts was also evaluated for abutment-level impressions. MATERIALS AND METHODS: A
      reference model with six internal-connection implant replicas placed in the
      completely edentulous mandibular arch and connected to multi-base abutments was
      fabricated from heat-curing acrylic resin. Forty impressions of the reference
      model were made, 20 each with polyether (PE) and polyvinylsiloxane (PVS)
      impression materials using the open tray technique. The PE and PVS groups were
      further subdivided into four subgroups of five each on the bases of splinting
      type: no splinting, bite registration PE, bite registration addition silicone, or
      autopolymerizing acrylic resin. The positional accuracy of the implant replica
      heads was measured on the poured casts using a coordinate measuring machine to
      assess linear differences in interimplant distances in all three axes. The
      collected data (linear and three-dimensional [3D] displacement values) were
      compared with the measurements calculated on the reference resin model and
      analyzed with nonparametric tests (Kruskal-Wallis and Mann-Whitney). RESULTS: No
      significant differences were found between the various splinting groups for both
      PE and PVS impression materials in terms of linear and 3D distortions. However,
      small but significant differences were found between the two impression materials
      (PVS, 91 MUm; PE, 103 MUm) in terms of 3D discrepancies, irrespective of the
      splinting technique employed. CONCLUSIONS: Casts obtained from both impression
      materials exhibited differences from the reference model. The impression material
      influenced impression inaccuracy more than the splinting material for multiple
      unit abutment-level impressions.

PMID- 24278920
TI  - Analysis of bacterial flora associated with peri-implantitis using obligate
      anaerobic culture technique and 16S rDNA gene sequence.
AB  - PURPOSE: To analyze and characterize the predominant bacterial flora associated
      with peri-implantitis by using culture techniques under obligate anaerobic
      conditions and 16S rDNA gene sequences. MATERIALS AND METHODS: Subgingival
      bacterial specimens were taken from 30 patients: control (n = 15), consisting of
      patients with only healthy implants; and test (n = 15), consisting of patients
      with peri-implantitis. In both groups, subgingival bacterial specimens were taken
      from the deepest sites. An anaerobic glove box system was used to cultivate
      bacterial strains. The bacterial strains were identified by 16S rDNA genebased
      polymerase chain reaction and comparison of the gene sequences. RESULTS: Peri
      implantitis sites had approximately 10-fold higher mean colony forming units (per
      milliliter) than healthy implant sites. A total of 69 different bacterial species
      were identified in the peri-implantitis sites and 53 in the healthy implant
      sites. The predominant bacterial species in the peri-implantitis sites were
      Eubacterium nodatum, E. brachy, E. saphenum, Filifactor alocis, Slackia exigua,
      Parascardovia denticolens, Prevotella intermedia, Fusobacterium nucleatum,
      Porphyromonas gingivalis, Centipeda periodontii, and Parvimonas micra. The
      predominant bacteria in healthy implant sites apart from Streptococcus were
      Pseudoramibacter alactolyticus, Veillonella species, Actinomyces israelii,
      Actinomyces species, Propionibacterium acnes, and Parvimonas micra. CONCLUSION:
      These results suggest that the environment in the depths of the sulcus showing
      peri-implantitis is well suited for growth of obligate anaerobic bacteria. The
      present study demonstrated that the sulcus around oral implants with peri
      implantitis harbors high levels of asaccharolytic anaerobic gram-positive rods
      (AAGPRs) such as E. nodatum, E. brachy, E. saphenum, Filifactor alocis, Slackia
      exigua, and gram-negative anaerobic rods, suggesting that conventional
      periodontopathic bacteria are not the only periodontal pathogens active in peri
      implantitis, and that AAGPRs may also play an important role.

PMID- 24278921
TI  - Impact of implantoplasty on strength of the implant-abutment complex.
AB  - PURPOSE: Implantoplasty, a procedure that is done to smooth contaminated implant
      surfaces, has been used in the treatment of peri-implantitis. It reduces the
      implant diameter, which might compromise the implant's strength. This in vitro
      study was designed to evaluate the effect of implantoplasty on implant strength.
      MATERIALS AND METHODS: Thirty-two tapered implants were used; half were 3.75 mm
      in diameter (narrow) and the other half were 4.7 mm in diameter (wide). All
      implants were connected to 20-degree angled abutments. The apical half of each
      implant was embedded in acrylic resin. Eight 3.75-mm- and eight 4.7-mm-diameter
      implants were randomly assigned to receive implantoplasty. The remaining implants
      did not receive implantoplasty (control group). Implantoplasty was performed with
      a series of diamond and polishing burs. The specimens were then loaded 30 degrees
      off-axis in a universal testing machine until fracture failure occurred. Bending
      and fracture strength values were recorded and analyzed statistically (alpha =
      .05). The fractured surfaces were evaluated under a scanning electron microscope.
      RESULTS: All narrow implants failed by fracture at the implant platform. The mean
      bending strength of narrow implants was statistically significantly reduced by
      implantoplasty (511.4 +/- 55.9 N versus 613.9 +/- 42.8 N). Implantoplasty did not
      affect the strength of wide implants; fracture failures occurred at the abutment
      screw. The fracture mode was ductile and the crack growth was oblique in
      direction, indicating complex stress distribution and concentration under
      loading. CONCLUSION: Within the limits of this study, implantoplasty appeared to
      weaken the strength of narrower implants. Therefore, this procedure should be
      performed with caution on narrower, freestanding implants that are subject to
      greater occlusal force (eg, posterior regions). Validation of these results is
      needed for different implant systems.

PMID- 24278922
TI  - The effect of keratinized mucosa width on peri-implant health: a systematic
      review.
AB  - PURPOSE: The aim of this systematic review was to investigate the effect of
      keratinized mucosa width (KMW) on clinical parameters of peri-implant health and
      stability. MATERIALS AND METHODS: Two independent reviewers conducted a
      comprehensive search to identify studies on human subjects reporting KMW as a
      bivariate factor (>= 2 mm and < 2 mm), along with mean pocket depth (PD),
      bleeding on probing (BOP), modified Bleeding Index (mBI), Gingival Index (GI),
      Plaque Index (PI), modified PI (mPI), and implant survival with a minimum follow
      up of 6 months after implant loading. Eight studies were included in the
      systematic review and seven in the metaanalyses to ascertain summary effects for
      differences in the aforementioned parameters among groups of KMW. RESULTS: Pooled
      analyses showed that GI, PI, and mPI were significantly higher in the group with
      KMW of < 2 mm, while mBI was also higher but only marginally significant. In
      contrast, PD was not significantly different between the two groups. Differences
      in BOP and implant survival rate could not be analyzed because of limited data
      availability. Heterogeneity was highly significant among the pooled studies for
      all investigated variables. CONCLUSION: Reduced KMW around implants appears to be
      associated with clinical parameters indicative of inflammation and poor oral
      hygiene. However, based on the selected evidence, the predictive value of KMW is
      limited.

PMID- 24278923
TI  - Matrix metalloproteinases 2, 3, 8, 9, and 13 in the peri-implant soft tissues
      around titanium and zirconium oxide healing caps.
AB  - PURPOSE: This human study sought to compare, from an immunohistochemical point of
      view, matrix metalloproteinases (MMPs) 2, 3, 8, 9, and 13 in the soft tissues
      around titanium and zirconium oxide healing caps. MATERIALS AND METHODS: Five
      patients participated in this study. All patients received 3.8 * 11-mm dental
      implants, which were left to heal in a nonsubmerged (single-stage) mode. Healing
      caps (3.8 mm in diameter and 3.0 mm in height) were inserted in all implants.
      Half of the implants were randomly supplied with standard, prefabricated caps of
      commercially pure titanium (control), while the other half were randomly provided
      with zirconium oxide caps (test). After a 6-month healing period, gingival biopsy
      specimens were obtained with a circular scalpel around the healing caps of both
      groups, without unscrewing or removing the healing caps, and the samples
      underwent immunohistochemical processing for MMPs 2, 3, 8, 9, and 13. RESULTS:
      Statistically significant differences were found in the values of MMP-8 in the
      cells of the inflammatory infiltrate, with higher values for the titanium
      samples. Statistically significantly higher values were found, also in the
      titanium samples, for MMP-9 in the endothelial cells of the blood vessels. No
      statistically significant differences were found for any other MMPs. CONCLUSIONS:
      The present results showed that the soft tissues around titanium healing caps
      underwent a higher rate of restorative processes, most probably correlated to the
      MMP levels observed in the tissues.

PMID- 24278924
TI  - Placement of implants with platform-switched Morse taper connections with the
      implant-abutment interface at different levels in relation to the alveolar crest:
      a short-term (1-year) randomized prospective controlled clinical trial.
AB  - PURPOSE: This study sought to prospectively evaluate changes in marginal bone
      levels and soft tissue dimensions around platform-switched, Morse taper
      connection implants placed with the implant-abutment interface (IAI) at different
      positions in relation to the alveolar crest. MATERIALS AND METHODS: Thirty
      patients in need of single-tooth rehabilitations were randomly assigned to three
      groups based on the position of the IAI in relation to the alveolar crest at the
      time of implant placement. Implants in groups 0, 1, and 2 (n = 10 in each group)
      were placed at the bone level or 1 mm and 2 mm below the buccal aspect of the
      alveolar crest, respectively. Four months later, the implants were restored with
      crowns. Clinical parameters were recorded at 4 and 12 months, and marginal bone
      levels were assessed radiographically at placement, 4 months, and 12 months.
      RESULTS: Mean marginal bone loss below the implant platform in group 0 implants
      was 0.18 +/- 0.27 mm at 4 months and 0.27 +/- 0.45 mm at 12 months. All implants
      in groups 1 and 2 exhibited no marginal bone loss below the implant platform,
      since the first bone-to-implant contact was located at or above the implant
      margin. At 12 months, implants in groups 1 and 2 exhibited greater mean bone loss
      above the implant platform compared to implants in group 0, but the differences
      were not statistically significant (group 0, 0.64 +/- 0.49 mm; group 1, 0.81 +/-
      0.31 mm; group 2, 1.20 +/- 0.68 mm). Implants in groups 1 and 2 exhibited a
      statistically significantly higher percentage of implant surfaces with bone on
      the implant platform compared to group 0 implants (90% versus 35%). CONCLUSIONS:
      In the present study, differences in peri-implant bone responses existed for
      implants placed with the IAI at different locations in relation to the alveolar
      crest.

PMID- 24278925
TI  - Correction of buccal dehiscence at the time of implant placement without barrier
      membranes: a retrospective cone beam computed tomographic study.
AB  - PURPOSE: To assess the clinical and tomographic findings of a grafting approach
      without barrier membranes to treat peri-implant buccal bone dehiscences at the
      time of implant placement. MATERIALS AND METHODS: This retrospective study was
      conducted on all patients who needed implant placement with buccal bone grafting
      and were treated consecutively between March 2007 and June 2010. Two different
      implant systems were used (PSI, Globtek; XiVE Plus, Dentsply/Friadent). All sites
      had thick soft tissue (> 2 mm). All bone dehiscences were completely grafted with
      biphasic calcium phosphate and covered only by a soft tissue flap. Cone beam
      computed tomographic images were used to assess vertical buccal bone loss by
      measuring the distance between the implant platform and the first buccal bone
      contact with the implant body. Statistical analysis (Mann-Whitney test) was
      carried out to compare the outcomes from the two different implant systems
      analyzed. RESULTS: Forty-one subjects (18 men, 23 women; mean age 57.3 +/- 10.4
      years) were selected and received 60 implants (52 delayed and 8 immediate
      placement). Mean follow-up was 26 months (range, 18 to 39 months). All 8
      immediate implants and 33 of the 52 delayed implants presented buccal bone loss
      from 0 to 0.5 mm. Only two delayed sites presented buccal bone loss over 2 mm. No
      significant differences were seen between the implant systems. The study implant
      cumulative success rate was 100% (mean follow-up, 26 months). CONCLUSION:
      Predictable outcomes can be obtained by grafting buccal bone dehiscence areas
      without barrier membranes in sites with a minimum soft tissue thickness greater
      than 2 mm.

PMID- 24278926
TI  - Piezoelectric alveolar ridge-splitting technique with simultaneous implant
      placement: a cohort study with 2-year radiographic results.
AB  - PURPOSE: Extended grafting procedures in atrophic ridges are invasive and time
      consuming and increase cost and patient morbidity. Therefore, ridge-splitting
      techniques have been suggested to enlarge alveolar crests. The aim of this cohort
      study was to report techniques and radiographic outcomes of implants placed
      simultaneously with a piezoelectric alveolar ridge-splitting technique (RST).
      Peri-implant bone-level changes (DeltaIBL) of implants placed with (study group,
      SG) or without RST (control group, CG) were compared. MATERIALS AND METHODS: Two
      cohorts (seven patients in each) were matched regarding implant type, position,
      and number; superstructure type; age; and gender and received 17 implants each.
      Crestal implant bone level (IBL) was measured at surgery (T0), loading (T1), and
      1 year (T2) and 2 years after loading (T3). For all implants, DeltaIBL values
      were determined from radiographs. Differences in DeltaIBL between SG and CG were
      analyzed statistically (Mann-Whitney U test). Bone width was assessed
      intraoperatively, and vertical bone mapping was performed at T0, T1, and T3.
      RESULTS: After a mean observation period of 27.4 months after surgery, the
      implant survival rate was 100%. Mean DeltaIBL was -1.68 +/- 0.90 mm for SG and 
      1.04 +/- 0.78 mm for CG (P = .022). Increased DeltaIBL in SG versus CG occurred
      mainly until T2. Between T2 and T3, DeltaIBL was limited (-0.11 +/- 1.20 mm for
      SG and -0.05 +/- 0.16 mm for CG; P = .546). Median bone width increased
      intraoperatively by 4.7 mm. CONCLUSIONS: Within the limitations of this study, it
      can be suggested that RST is a well-functioning one-stage alternative to extended
      grafting procedures if the ridge shows adequate height. DeltaIBL values indicated
      that implants with RST may fulfill accepted implant success criteria. However,
      during healing and the first year of loading, increased IBL alterations must be
      anticipated.

PMID- 24278927
TI  - Quantitative percussion diagnostics and bone density analysis of the implant-bone
      interface in a pre- and postmortem human subject.
AB  - PURPOSE: It has been hypothesized that a correlation exists between the density
      of surrounding cortical bone and the stability of an implant under percussion
      loading that can be used to quantify the implant's osseointegration. The purpose
      of the present research was to explore whether quantitative percussion testing of
      dental implants gives reasonable indications of the level of osseointegration
      that are consistent with bone configuration and its influence on osseointegration
      quality. MATERIALS AND METHODS: Data from percussion testing of a live human
      subject, obtained using the Periometer, were compared with corresponding bone
      density estimates from high-resolution computed tomography images and postmortem
      percussion probe data. RESULTS: The results confirm the hypothesis that the
      nature of an implant's response to percussion is determined by its cortical bone
      support. CONCLUSIONS: The findings suggest that the cortical bone supporting the
      crestal and apical regions of the implant is primarily responsible for structural
      stability.

PMID- 24278928
TI  - Photofunctionalized dental implants: a case series in compromised bone.
AB  - PURPOSE: Ultraviolet (UV) light treatment of titanium, or photofunctionalization,
      has been shown to enhance its osteoconductivity in animal and in vitro studies,
      but its clinical performance has yet to be reported. This clinical case series
      sought to examine the effect of photofunctionalization on implant success,
      healing time, osseointegration speed, and peri-implant marginal bone level
      changes at 1 year after restoration. MATERIALS AND METHODS: Four partially
      edentulous patients were included in the study. Seven implants with identical
      microroughened surfaces were photofunctionalized with UV light for 15 minutes.
      Osseointegration speed was calculated by measuring the increase in implant
      stability quotient (ISQ) per month. Marginal bone levels were evaluated
      radiographically at crown placement and at 1 year. RESULTS: All implants placed
      into fresh extraction sockets, vertically augmented bone, simultaneously
      augmented sinuses, or the site of a failing implant remained functional and
      healthy at 1 year, even with an earlier loading protocol (2.1 to 4.5 months).
      ISQs of 48 to 75 at implant placement had increased to 68 to 81 at loading. In
      particular, implants with low primary stability (initial ISQ < 70) showed large
      increases in ISQ. The speed of osseointegration of photofunctionalized implants
      was considerably greater than that of as-received implants documented in the
      literature. Mean marginal bone levels were -0.35 +/- 0.71 mm at crown placement
      and had significantly increased to 0.16 +/- 0.53 mm at 1 year, with coronal gains
      in marginal bone level that surpassed the implant platform. No implants showed
      marginal bone loss. CONCLUSIONS: Within the limits of this study,
      photofunctionalization expedited and enhanced osseointegration of commercial
      dental implants in various clinically challenging/compromised bone conditions.
      Photofunctionalization resulted in preservation--and often a gain--of marginal
      bone level, and long-term large-scale clinical validation is warranted.

PMID- 24278929
TI  - A randomized controlled clinical trial of two types of tapered implants on
      immediate loading in the posterior maxilla and mandible.
AB  - PURPOSE: The aim of this study was to compare clinical outcomes and stability
      following immediate loading of two types of tapered implants in the partially
      edentulous posterior maxilla and mandible. MATERIALS AND METHODS: A randomized
      controlled trial with 1 year of follow-up was performed on participants missing
      two consecutive teeth in a posterior quadrant with tapered implants with a hybrid
      textured surface. Group 1 received Osstem TSIII HA implants, and group 2 received
      Zimmer TSV implants. Group 1 implants were 4.5 or 5.0 mm in diameter, and group 2
      implants were 4.7 mm in diameter; all implants were 10 mm long. Subjects received
      provisional restorations within 48 hours. Definitive restorations were provided 3
      months (mandible) or 6 months (maxilla) later. Outcome measures were survival and
      success rates, marginal bone level change, implant stability quotient, and peri
      implant soft tissue indices. RESULTS: Fifty participants completed the trial
      (group 1: 52 implants in 26 patients; group 2: 48 implants in 24 patients). The
      success rates were similar--98.1% in group 1 and 97.9% in group 2--at 12 months
      after immediate loading, but marginal bone loss was significantly different
      according to the implant design. Implant stability increased significantly in
      both arches. There were no significant differences in soft tissue indices between
      implant systems. CONCLUSION: If high primary stability is acquired, tapered
      implants with hybrid textured surfaces are predictable for immediate loading in
      the posterior maxilla and mandible. In spite of the influence of implant design
      on marginal bone loss, all tapered implants showed successful clinical outcomes
      and stability in immediate loading.

PMID- 24278930
TI  - Assessment of removed dental implants in Finland from 1994 to 2012.
AB  - PURPOSE: The National Institute for Health and Welfare in Finland (THL) has
      maintained the Finnish Dental Implant Register since April 1994. The aim of this
      study was to use the Dental Implant Register to assess the influence of patient
      characteristics and background factors on dental implant removals in Finland from
      1994 to 2012. MATERIALS AND METHODS: THL granted permission to access the Finnish
      Dental lmplant Register (1994 to 2012) and assess the following factors: total
      implant placements, total implant removals, time from implant placement to
      removal, implant types, implant lengths, placed and failed implants by jaw and
      tooth type, and patient sex and age. RESULTS: A total of 198,538 dental implants
      (51 different types) were placed between 1994 and 2012. A total of 3,318 (1.7%)
      of the placed implants were removed during the observation period. A total of
      1,856 (1.8%) of the placed implants were removed from the maxilla and 1,462
      (1.5%) from the mandible (P < .001). A slight difference in the sex distribution
      concerning implant failures (3.1% in men vs 2.3% in women) was observed. The
      median removal time was 247 days postoperatively (range 0 to 11,383 days), and
      one-third of the implants were removed within the first 142 days. Most of the
      placed implants were 10 mm or longer (93.3%) with 12 mm being the most commonly
      used length (23.9%). Shorter implants (8 mm or less) were removed more often
      (2.5% removal rate) than 9 mm or longer implants (1.5% removal rate). The IMZ
      Implant system demonstrated the highest overall removal rates (8.5%), while
      Branemark Nobel Direct (0.6%) demonstrated the lowest removal rates. Of the most
      commonly placed implant types (together comprising 60.9% of all implants placed),
      the Straumann (1.2%) and the Astra Implant (1.2%) systems demonstrated equally
      low removal rates. CONCLUSIONS: The overall dental implant removal rates in
      Finland are low. Only slight differences in gender and implant position were
      observed.

PMID- 24278931
TI  - Comparison of retention and stability of implant-retained overdentures based upon
      implant number and distribution.
AB  - PURPOSE: The purpose of this investigation was to evaluate the effects of number
      and distribution of implants upon in vitro dislodging forces to a simulated
      implant-supported overdenture and to examine differences between several
      different attachment systems. MATERIALS AND METHODS: An experiment was undertaken
      utilizing a model simulating a mandibular edentulous ridge with dental implants
      in positions on the model approximating tooth positions in the natural dentition.
      A cobalt-chromium-cast testing framework was used to measure the peak load
      required to disconnect an attachment. Four different types of commercially
      available attachments were used in various positions on the model in sequence to
      evaluate the effects of retention and stability of overdentures based on implant
      number and distribution: (1) ERA, (2) O-Ring, (3) Locator, and (4) Ball. For each
      group, 10 measurements were made of peak dislodging forces. Means were calculated
      and differences among the systems, directions, and groups were identified using a
      repeated measured analysis of variance (alpha = .05). RESULTS: The interactions
      between the attachment system, direction of force, and implant number and
      distribution were statistically significant. Vertical dislodging forces of the
      simulated overdenture prosthesis increased with additional widely spaced
      implants. Oblique dislodging forces of the simulated prosthesis increased with
      additional widely spaced implants except in the two-implant model with all
      attachments, and in the four-implant groups with Locator attachments.
      Anteroposterior dislodging forces of a simulated overdenture prosthesis increased
      with additional widely spaced implants except in the four-implant groups with
      Ball and Locator attachments. Ball attachments reported the highest levels of
      retention and stability followed by Locator, O-Ring, and ERA. CONCLUSIONS: Within
      the limitations of this study, retention and stability of an implant overdenture
      prosthesis are significantly affected by implant number, implant distribution,
      and abutment type.

PMID- 24278932
TI  - In vivo osteogenesis and in vitro Streptococcus mutans adherence: porous-surfaced
      cylindrical implants vs rough-surfaced threaded implants.
AB  - PURPOSE: To analyze and compare bone apposition at the interface of commercially
      available rough-surfaced, threaded implants with porous-surfaced, cylindrical
      implants after several healing periods in a rabbit model. In addition, the study
      aimed to elucidate the influence of the implant surface configuration on
      Streptococcus mutans adherence. MATERIALS AND METHODS: Using a powder metallurgy
      technique, a new method was developed to produce titanium implants with a dense
      core and porous surface to increase bone-implant contact (BIC). Sixty implants
      were placed in 15 rabbits. In each rabbit, two experimental and two control
      implants were placed in the right or left tibia. The experimental implants were
      inserted under pressure into the surgical cavity, while the control implants were
      self-threaded. The rabbits were euthanized at 4, 8, and 12 weeks postinsertion
      for undecalcified histologic processing and morphometric evaluation of BIC.
      Additionally, 16 implants, eight experimental and eight control, were incubated
      with S. mutans to evaluate adherence for each type of implant. Analysis of
      variance with repeated measures and the Student t test were applied,
      respectively. RESULTS: Histology showed intimate bone-implant interfaces without
      soft tissue intervention in both groups. Porous-surfaced cylindrical implants
      showed a higher BIC (72.41% +/- 9.47%) than the rough-surfaced screw implants
      (61.23% +/- 14.12%) (P = .013), while no significant difference in S. mutans
      adherence occurred (P = .351). The implant type effect was more pronounced in the
      4-week healing period groups (P = .029). The percentage of BIC was similar
      throughout the healing periods (P = .333), but gradually increased over time.
      CONCLUSION: Within the limitations of this study, the results suggest that the
      new implant design increased BIC without provoking greater S. mutans adherence.

PMID- 24278933
TI  - In vitro effects of a chemically modified titanium surface on ethanol-exposed
      osteoblasts.
AB  - PURPOSE: No clinical evidence-based data on a possible negative influence of
      osteopenia and harmful lifestyles on implant osseointegration have been published
      to date. However, chronic alcohol abuse has been related to a progressive
      osteoporotic state. The continuous effort on developing better performing
      surfaces might offer improvement in osseointegration rates in conditions of poor
      bone quality. The aim of the present study was to investigate, in vitro, the
      behavior of osteoblasts obtained from rats exposed to ethanol vapor for 7 weeks
      and cultured on an innovative titanium surface achieved by a double anodic spark
      deposition. MATERIALS AND METHODS: Ethanol-exposed and unexposed (control)
      osteoblasts were cultured on an anodic spark-deposited titanium surface and
      compared to those cultured on an acid-etched one. Cell proliferation and
      synthesis of alkaline phosphatase, osteocalcin, collagen I, transforming growth
      factor-beta1, interleukin-6, and tumor necrosis factor-alpha were measured at 3,
      7, and 14 days of culture. RESULTS: When cultured on the anodic spark-deposited
      titanium surface, ethanol-exposed osteoblasts recovered proliferation impairment.
      Anodic spark-deposited titanium surfaces significantly improved both ethanol
      exposed and unexposed osteoblast bioactivity, particularly with regard to
      alkaline phosphatase and transforming growth factor-beta1. Moreover, interleukin
      6 release for ethanol-exposed osteoblasts was significantly reduced by the anodic
      spark-deposited titanium surface. CONCLUSION: Proliferative and synthetic cell
      processes altered by ethanol contact were positively and partially restored by
      contact with the tested innovative surface.

PMID- 24278934
TI  - Bone formation at porous titanium implants coated with multiple layers of
      recombinant human bone morphogenetic protein-2 cDNA plasmid in the posterior
      mandible in dogs.
AB  - PURPOSE: The objective of this study was to evaluate peri-implant bone formation
      and osseointegration at titanium implants coated with multiple layers of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) cDNA placed into canine
      mandibles. MATERIALS AND METHODS: The rhBMP-2 plasmid was assembled on
      sandblasted/dual-acid-etched pure titanium implant surfaces using layer-by-layer
      assembly. The rhBMP-2 plasmid-coated implants were placed into the edentulous
      posterior mandibles of 12 adult beagle dogs. Implants without the rhBMP-2 plasmid
      coating served as controls. Treatments were randomized between jaw quadrants, and
      four implants were placed in each mandibular quadrant. After 4, 8, and 12 weeks
      in situ, mandibles were retrieved and prepared for removal torque testing and
      histomorphometric evaluation. RESULTS: Eight layers of rhBMP-2 plasmid were
      assembled onto the implant surfaces. Histomorphometric analysis showed that,
      after 4 and 8 weeks of healing, the intrathread bone area (BA) was slightly
      higher for test implants (54.21% and 59.56%) than for control implants (38.48%
      and 54.98%), respectively, but no statistically significant differences were seen
      at any time points. Mechanical tests showed that the mean removal torque values
      of the rhBMP-2 cDNA-coated implants were greater than those of the control
      implants after 8 weeks of healing (91 Ncm versus 61 Ncm; P = .31). CONCLUSION:
      Coating implants with multiple layers of an rhBMP-2 plasmid did not promote peri
      implant bone formation and osseointegration in this model.

PMID- 24278935
TI  - Biocompatibility and microstructural analysis of osteopromotive property of
      allogenic demineralized dentin matrix.
AB  - PURPOSE: Bone grafting materials and methods have been used to compensate
      anatomical limitations and improve ridge and sinus structure for implant
      placement. The objective of this study was to evaluate the osteopromotive
      property of allogenic demineralized dentin matrix (DDM) as a bone grafting
      material using micro-computed tomography and blood biomarkers. MATERIALS AND
      METHODS: Two surgical bone defects were created on the skull of 30 female New
      Zealand White rabbits. Experimental defects in 24 rabbits were filled with
      allogenic DDM applying guided bone regeneration technique, while the control
      defects were covered by membrane without receiving the graft. In the remaining
      six rabbits, both defects were left empty and these rabbits served as control for
      blood biomarkers. The 24 experimental rabbits were sacrificed after 15, 30, 60,
      and 90 days (n = 6 at each time point). Blood samples were collected from all
      rabbits at the baseline, 48 hours postsurgery, and at each time point. RESULTS:
      Bone thickness was significantly higher in the experimental group at all time
      points. Micro-computed tomography results showed increased bone mass and superior
      bone quality in the experimental group. At all time points except for 48 hours
      postsurgery, the white blood cell count was numerically higher in control rabbits
      compared to experimental rabbits, suggesting a lack of inflammation or infection
      due to allogenic DDM. Bone-specific alkaline phosphatase activities were lower in
      both experimental and control groups at all time points in comparison to baseline
      values, which is indicative of either a lower rate of bone formation or bone
      turnover. CONCLUSIONS: Within the limitations of this study, allogenic
      demineralized dentin matrix significantly increased bone mass and improved bone
      quality without causing an inflammatory reaction or infection.

PMID- 24278936
TI  - The effect of implant connection length on the dimensional impression accuracy of
      inclined implants.
AB  - PURPOSE: Accurate recording of implant locations is essential for precise
      passively fitting prostheses with proper support. This in vitro study evaluated
      the accuracy of impressions made of parallel and nonparallel implants with
      different lengths of impression coping connections. MATERIALS AND METHODS: A
      reference model containing four internal-connection implant analogs (two at 0
      degrees and two at 30 degrees in relation to the perpendicular line) was
      fabricated. Thirty medium-consistency silicon impressions of this model were made
      using the open-tray impression technique. Three groups of 10 specimens each were
      made with different impression coping connection lengths (2, 1.5, or 1 mm).
      Impressions were poured with type IV stone. The positional accuracy of the
      implant replica heads in the x-, y-, and z-axes was evaluated using a coordinate
      measuring machine, and measurements were compared with the obtained dimensions
      from the reference model. Data were analyzed with two-way analysis of variance
      (alpha = .05). RESULTS: There was no significant difference in impression
      accuracy, regardless of the lengths of the impression connections. Additionally,
      there was no significant difference between the impression accuracy of inclined
      and straight implants, except in the y-axis (P = .006). CONCLUSIONS: Within the
      limitations of this study, the accuracy of implant impressions did not differ for
      different lengths of transfer coping connections of inclined and straight
      implants.

PMID- 24278937
TI  - Mechanical comparison of experimental conical-head abutment screws with
      conventional flat-head abutment screws for external-hex and internal tri-channel
      implant connections: an in vitro evaluation of loosening torque.
AB  - PURPOSE: This study compared the loosening torque of experimental conical-head
      abutment screws to that of conventional flat-head screws of implants with
      external-hex (EH) and internal tri-channel (IT) connections before and after
      mechanical loading. MATERIALS AND METHODS: Forty-four implant/screw/abutment
      assemblies were divided into four groups: EH/flat-head screw (EH), IT/flat-head
      screw (IT), EH/conical-head screw (EHCS), and IT/conical-head screw (ITCS). Three
      assemblies from each group were analyzed in a stereoscopic magnifier and then
      returned to their respective groups. One assembly was removed from each group and
      transversely sectioned for optical microscopy analysis. Abutments were tightened
      at 32 Ncm of torque; after 10 minutes, loosening torque was measured. The same
      abutments were then retightened with 32 Ncm of torque; after 10 minutes, they
      were mechanically loaded for 300,000 cycles and loosening torque was again
      measured. Data were collected and an exploratory analysis was performed.
      Comparisons were made by orthogonal contrasts using a linear mixed effects model
      (random and fixed effects). RESULTS: Comparisons before mechanical cycling showed
      significant differences between groups except for EH vs IT and EHCS vs ITCS.
      After mechanical cycling, only the comparisons EH vs IT and EHCS vs ITCS showed
      no significant differences. Considering the same group, before and after
      mechanical cycling, all comparisons showed significant differences. CONCLUSIONS:
      The shape of the abutment screw head significantly influenced loosening torque:
      conical-head screws showed higher loosening torque values than conventional flat
      head screws before and after loading. The implant/abutment connection design
      exerted no significant influence on loosening torque.

PMID- 24278938
TI  - Recombinant human bone morphogenetic protein-2 confined by an imperforate
      titanium shell over high-profile dental implants in rabbit tibiae: a pilot bone
      augmentation study.
AB  - PURPOSE: To evaluate the use of a nonperforated titanium occlusive device over a
      bone morphogenetic protein-2 in an absorbable collagen sponge (BMP-2/ACS) in
      grafting the bone around high-profile (ie, supracrestal) dental implants in
      rabbit tibiae. MATERIALS AND METHODS: Eight New Zealand white rabbits were used
      for the experiment. Two implants were placed in the right tibia of each rabbit,
      with 4 mm of each implant placed supracrestally ("high-profile" placement) in
      four groups of two rabbits each: control, titanium shell only, titanium shell
      over buffered collagen, and titanium shell over BMP-2/ACS. The animals were
      sacrificed after 3 or 6 weeks. Calcified and nondecalcified histologic
      preparation was carried out to evaluate bone formation and degree of
      osseointegration. RESULTS: Three of the eight animals developed tibial fractures.
      The two BMP-2 test animal tibiae remained intact, with the 3-week specimen
      showing very little bone formation inside or outside of the titanium chamber and
      the 6-week specimen showing bone mostly outside of the chamber. CONCLUSION: The
      placement of BMP-2 beneath an occlusive nonperforated titanium shell next to a
      high-profile implant did not result in significant bone formation. .

PMID- 24278939
TI  - The use of a magnesium-based bone cement to secure immediate dental implants.
AB  - PURPOSE: The use of a magnesium-based bone cement, OsteoCrete, has shown promise
      as a means to secure bone and tendon-to-bone connections in orthopedic medicine.
      The presence of a bone cement to fill the residual socket and stabilize a dental
      implant during healing could make immediate implant placement in molar sites more
      predictable. The aim of this study was to determine whether this magnesium-based
      bone cement can be used predictably for this purpose. MATERIALS AND METHODS: The
      mandibular third premolars and first molars were extracted bilaterally from four
      mongrel dogs (60 to 80 lb each). Implants were placed in each extraction socket
      and supported by only 2 to 3 mm of apical furcation bone. OsteoCrete bone cement
      was placed randomly for implant stabilization in half of the sites. Clinical
      healing was evaluated until the 4-month time point. All animals were then
      sacrificed, and mandibular en bloc resection was performed for histologic
      evaluation of the biologic response and bone-to-implant contact. RESULTS:
      Clinically, healing showed a poor response when the test site implant was left
      exposed in a one-stage manner. No statistically significant difference was noted
      in bone-to-implant contact (52% in test sites versus 44% in control sites).
      Histologic specimens showed no adverse biologic response to the material but only
      minimal replacement at 4 months. CONCLUSIONS: OsteoCrete bone cement was
      successful in stabilizing the immediate dental implant in a large extraction
      socket when placed in a closed environment in the dog model but did not show a
      benefit as compared to controls. The limited data warrant further studies to
      determine the further potential of this material.

PMID- 24278940
TI  - Effects of the permeability of shields with autologous bone grafts on bone
      augmentation.
AB  - PURPOSE: The objective of this study was to histologically evaluate and compare
      the effects of the permeability of shields on bone augmentation in a rabbit
      calvarial model. MATERIALS AND METHODS: Twelve adult male Japanese white rabbits
      were used for the study. Each received four titanium cylinders, which were placed
      into perforated slits made in the outer cortical bone of the calvaria and filled
      with autologous iliac bone. The tops of the cylinders were randomly covered with
      the following test materials: (1) uncovered (control), (2) a titanium mesh, (3)
      an expanded polytetrafluoroethylene (e-PTFE) membrane, or (4) a titanium plate.
      After 8 weeks, the animals were sacrificed, and ground sections were obtained for
      histomorphometric analysis. RESULTS: There was no significant difference in
      augmented bone volume among all groups. However, the distribution of augmented
      bone in the cylinders differed among the groups. In the uncovered control, there
      was significantly less augmented bone in the upper third of the cylinder than in
      the middle or lower thirds. Findings were similar for the titanium mesh group and
      the e-PTFE membrane group, with significantly less augmented bone in the upper
      third than in the middle or lower thirds. In the titanium plate group, there was
      no significant difference in augmented bone among the upper, middle, and lower
      thirds. The differences among the upper, middle, and lower thirds of the cylinder
      were smaller in the order of titanium plate, e-PTFE membrane, titanium mesh, and
      uncovered control. CONCLUSION: The use of low-permeability shields resulted in
      small differences in the distribution of bone structure in the present bone
      augmentation model.

PMID- 24278941
TI  - Posterior maxillary sandwich osteotomy combined with sinus grafting with bone
      morphogenetic protein-2 for alveolar reconstruction for dental implants: report
      of four cases.
AB  - Four patients underwent posterior sandwich osteotomy combined with sinus floor
      grafting using bone morphogenetic protein-2 and other grafting materials. The
      patients were treated over a period of 4 years. Two to four implants were placed
      in each site subsequently. Of the 12 implants placed, none failed. Alveolar crest
      bone levels appeared to be stable over time, with an average vertical gain of
      about 5 mm. Overall vertical gain, including the sinus graft, exceeded 13 mm in
      all patients. The procedure appears to hold promise for combined vertical
      alveolar defects and prominent pneumatization of the posterior maxilla. 

PMID- 24278942
TI  - In vitro and in vivo osteoinductive and osteoconductive properties of a synthetic
      bone substitute.
AB  - PURPOSE: The present study tested a recently introduced bone substitute material
      (BSM) with a novel structure to determine its osteoinductive and osteoconductive
      properties in vitro and in vivo. The specific aims were to determine the
      microstructure of the as-manufactured BSM, as analyzed with scanning electron
      microscopy, and to characterize different cellular interactions. MATERIALS AND
      METHODS: Human bone marrow stromal cells were cultured in the presence of the
      BSM. In vitro, attachment of osteoblastlike cells (SAOS-2) to the BSM was
      observed with the scanning electron microscope. The expression of genes related
      to osteogenic differentiation (alkaline phosphatase, bone sialoprotein, type I
      collagen, and osteocalcin) was determined by reverse-transcriptase polymerase
      chain reaction. In vivo, bone formation was examined with a murine model of
      ectopic bone formation through histology and computed tomographic scanning by
      using tissue-engineered constructs with the BSM and ovine bone marrow stromal
      cells. RESULTS: Early cellular attachment could be detected as early as 6 hours.
      Cellular morphology developed in the following 66 hours toward a starlike
      appearance. Human bone marrow stromal cells cultured in the presence of the BSM
      showed no reduction in their viability. Osteocalcin was up-regulated during cell
      culturing, demonstrating an osteoinductive effect of BSM. Histologic and computed
      tomographic analyses showed the formation of new bone surrounding BSM particles,
      and a vascular meshwork was observed in the porosity of the particles.
      CONCLUSION: The analyzed bone substitute of synthetic origin presented
      osteoinductive properties that may exert a differentiative stimulus upon
      osteoprogenitor cells. The tested material allowed cellular adhesion of
      osteoblastlike cells and, following tissue construct implantation in vivo,
      supported the formation of new bone.

PMID- 24278943
TI  - Osteoblastic differentiation of human stem cells derived from bone marrow and
      periodontal ligament under the effect of enamel matrix derivative and
      transforming growth factor-beta.
AB  - PURPOSE: To increase the understanding of the applicability of biomaterials and
      growth factors in enhancing stem cell-based bone regeneration modalities, this
      study evaluated the effects of enamel matrix derivative (EMD) and recombinant
      human transforming growth factor-beta (rhTGF-beta) on osteoblastic
      differentiation of human bone marrow mesenchymal stem cells (hBMSCs) as well as
      human periodontal ligament stem cells (hPDLSCs). MATERIALS AND METHODS: hBMSCs
      and hPDLSCs were obtained, and identification of stem cell surface markers was
      performed according to the criteria of the International Society for Cellular
      Therapy. Each group of stem cells was separately treated with a serial dilution
      of EMD (10, 50, and 100 MUg/mL) or rhTGF-beta (10 ng/mL). Osteoblastic
      differentiation was examined through in vitro matrix mineralization by alizarin
      red staining, and mRNA expression of osteopontin and osteonectin was determined
      by quantitative reverse-transcriptase polymerase chain reaction. hPDLSCs were
      further assessed for osteocalcin mRNA expression. Stem cells cultured in
      osteogenic medium were employed as a standard positive control group. RESULTS: In
      none of the experimental groups were bone-related mRNAs detected subsequent to
      treatment with EMD for 5, 10, and 15 days. Alizarin red staining on day 21 was
      negative in EMD-treated BMSC and PDLSC cultures. In rhTGF-beta-supplemented BMSC
      culture, expression of osteonectin mRNA was demonstrated on day 15, which was
      statistically comparable to the positive control group. Nevertheless,
      extracellular matrix mineralization was inhibited in both groups of stem cells.
      CONCLUSIONS: Within the limitations of this study, it could be concluded that EMD
      with a concentration of 10, 50, or 100 MUg/mL has no appreciable effect on
      osteoblastic differentiation of BMSCs and PDLSCs. Application of rhTGF-beta
      increased osteonectin mRNA expression in BMSCs. This finding corroborates the
      hypothesis that TGF-beta might be involved in early osteoblastic maturation.

PMID- 24278944
TI  - Mesenchymal dental stem cells for tissue regeneration.
AB  - Two types of dentition are generated in a human's lifetime: the primary
      dentition, followed by the permanent dentition. Undoubtedly, teeth are essential
      for speech and mastication in both dentitions, but it is becoming apparent that
      dental pulp also plays a role in harboring mesenchymal stem cells (MSCs). To
      date, three kinds of MSCs derived from dental pulp have been established:
      permanent tooth, primary tooth, and immature apical papilla. The dental pulp from
      primary teeth is considered a particularly good source of MSCs; it can be
      obtained from extracted primary teeth, of which humans have 20. The past decade
      has seen many reports of dental pulp-derived MSCs, and the field is becoming
      increasingly popular. The present article describes the characterization of
      dental pulp-derived MSCs from primary teeth. It also discusses future banking
      activity of primary teeth, because it is known that dental pulp-derived MSCs have
      similar potential to those derived from bone marrow. Methods with which to
      optimize the cryopreservation process should therefore be investigated, because
      banked dental pulp may provide a great resource in future regenerative medicine. 

PMID- 24278945
TI  - Regulatory effects of inflammatory and biomechanical signals on regenerative
      periodontal healing.
AB  - Periodontitis is a chronic inflammatory disease associated with loss of
      periodontal attachment, collagen, and alveolar bone. Regeneration of periodontal
      tissues can be supported by the local application of enamel matrix derivative
      (EMD). However, periodontal regeneration remains a major and often unpredictable
      challenge as the result of a number of unknown factors. The authors' in vitro
      studies revealed that EMD stimulated the wound fill rate, proliferation, and
      adhesion of periodontal ligament (PDL) cells. However, in the presence of an
      inflammatory environment or biomechanical loading, the beneficial effects of EMD
      decreased significantly. EMD also stimulated the synthesis of growth factors and
      collagen, as well as calcium deposition, in PDL cell cultures. These beneficial
      effects of EMD on PDL cells were also significantly diminished by inflammation
      and biomechanical forces, respectively. The findings suggest that critical PDL
      cell functions pertinent to periodontal regeneration are reduced in an
      inflammatory environment and under biomechanical loading. Therefore, effective
      anti-infectious and anti-inflammatory periodontal treatment before the
      application of EMD may be critical to ensure the full regenerative capacity of
      the PDL tissue. Furthermore, occlusal loading of EMD-treated teeth, at least
      immediately following surgery, should be minimized to obtain optimal regenerative
      healing results. A better understanding of the interactions of growth factors and
      biomechanical signals will result in more powerful regenerative therapeutic
      strategies. 

PMID- 24278946
TI  - Adipose-derived stem cells and periodontal tissue engineering.
AB  - Innovative developments in the multidisciplinary field of tissue engineering have
      yielded various implementation strategies and the possibility of functional
      tissue regeneration. Technologic advances in the combination of stem cells,
      biomaterials, and growth factors have created unique opportunities to fabricate
      tissues in vivo and in vitro. The therapeutic potential of human multipotent
      mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose
      tissue, has generated increasing interest in a wide variety of biomedical
      disciplines. These cells can differentiate into a variety of tissue types,
      including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have
      some advantages compared with other sources of stem cells, most notably that a
      large number of cells can be easily and quickly isolated from adipose tissue. In
      current clinical therapy for periodontal tissue regeneration, several methods
      have been developed and applied either alone or in combination, such as enamel
      matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic
      bone grafts, and growth factors. However, there are various limitations and
      shortcomings for periodontal tissue regeneration using current methods. Recently,
      periodontal tissue regeneration using MSCs has been examined in some animal
      models. This method has potential in the regeneration of functional periodontal
      tissues because the various secreted growth factors from MSCs might not only
      promote the regeneration of periodontal tissue but also encourage
      neovascularization of the damaged tissues. Adipose-derived stem cells are
      especially effective for neovascularization compared with other MSC sources. In
      this review, the possibility and potential of adipose-derived stem cells for
      regenerative medicine are introduced. Of particular interest, periodontal tissue
      regeneration with adipose-derived stem cells is discussed. 

PMID- 24278947
TI  - The role of systemically delivered bone marrow-derived mesenchymal stem cells in
      the regeneration of periodontal tissues.
AB  - PURPOSE: Recent studies have shown that periodontal ligament stem cells (PDLSCs)
      play a key role in periodontal regeneration. However, the origin of these cells
      remains unclear. Meanwhile, bone marrow is thought to be the most common source
      of adult stem cells in many tissues and organs. Thus, the present investigation
      sought to determine whether systemically delivered bone marrow-derived
      mesenchymal stem cells (BM-MSCs) could participate in periodontal regeneration
      and differentiate into periodontal-specific cells and to explore the origin of
      PDLSCs. METHODS: Enhanced green fluorescent protein (EGFP)-labeled BMMSCs were
      delivered into lethally irradiated rats by intra-bone marrow (IBM)
      transplantation. Four weeks after transplantation, periodontal defects with and
      without infection of anaerobic cultured Porphyromonas gingivalis were
      established. The animals were killed 1, 2, 4, or 6 weeks after periodontal defect
      surgery. Histomorphologic analysis, direct observation with the fluorescence
      microscope, and immunohistochemical staining were performed to evaluate the
      localization and differentiation of BM-MSCs. RESULTS: EGFP-positive BM-MSCs could
      be observed as early as 1 week after surgery, and the number of EGFP-positive
      cells reached a maximum at 2 weeks. Meanwhile, EGFP-positive cells were observed
      in the newly formed bone, PDL, and cementum 4 weeks after surgery.
      Immunohistochemical staining verified that EGFP-positive BM-MSCs could
      differentiate into osteoblasts. CONCLUSIONS: These findings provide direct
      evidence that BM-MSCs can participate in and modulate periodontal regeneration.

PMID- 24278948
TI  - Molecular assessment of osseointegration in vivo: a review of the current
      literature.
AB  - This paper reports on the results of a structured review of the literature
      concerning in vivo molecular assessment of osseointegrated endosseous dental
      implants. A search of electronic databases was performed up to and including
      August 2011. Thirty articles met the inclusion criteria. A descriptive evaluation
      and analysis of the gene expression data concerning the process of
      osseointegration were performed. Broad consensus was observed among the study
      results, perhaps as a result of the similar targeted gene expression events. More
      recent investigations using gene arrays or gene profiling techniques offer new
      insights into the fundamental molecular events that support the osseointegration
      process. Evidence for the influence of surface topography on osteogenesis and
      osteoinduction has been reported. Additional investigations are required to
      further solidify the functional associations between individual or orchestrated
      gene expression events and the clinical result of osseointegration. 

PMID- 24278949
TI  - Nanotechnology for dental implants.
AB  - With the advent of nanotechnology, an opportunity exists for the engineering of
      new dental implant materials. Metallic dental implants have been successfully
      used for decades, but they have shortcomings related to osseointegration and
      mechanical properties that do not match those of bone. Absent the development of
      an entirely new class of materials, faster osseointegration of currently
      available dental implants can be accomplished by various surface modifications.
      To date, there is no consensus regarding the preferred method(s) of implant
      surface modification, and further development will be required before the ideal
      implant surface can be created, let alone become available for clinical use.
      Current approaches can generally be categorized into three areas: ceramic
      coatings, surface functionalization, and patterning on the micro- to nanoscale.
      The distinctions among these are imprecise, as some or all of these approaches
      can be combined to improve in vivo implant performance. These surface
      improvements have resulted in durable implants with a high percentage of success
      and long-term function. Nanotechnology has provided another set of opportunities
      for the manipulation of implant surfaces in its capacity to mimic the surface
      topography formed by extracellular matrix components of natural tissue. The
      possibilities introduced by nanotechnology now permit the tailoring of implant
      chemistry and structure with an unprecedented degree of control. For the first
      time, tools are available that can be used to manipulate the physicochemical
      environment and monitor key cellular events at the molecular level. These new
      tools and capabilities will result in faster bone formation, reduced healing
      time, and rapid recovery to function. 

PMID- 24278950
TI  - A novel dental implant system with an internal port for endoscopic closed sinus
      augmentation: a feasibility study in pigs.
AB  - PURPOSE: This study describes the use of an innovative dynamic implant valve
      approach (DIVA) for dental implant placement and sinus augmentation procedures.
      MATERIALS AND METHODS: The DIVA implant system was tested in vitro for leakage
      and mechanical fatigue. A closed sinus elevation procedure with a gel-type bone
      substitute was performed using the DIVA implant in a swine model (n = 6).
      Implants were placed and evaluated radiographically and histologically. RESULTS:
      Elevation of the maxillary sinus membrane and augmentation were performed in a
      simple, minimally invasive fashion. Histologic analyses demonstrated complete
      sealing of the DIVA implant and excellent osseointegration. CONCLUSION: The DIVA
      can be used as a simplified viable option for dental implantation and
      augmentation procedures. Hermetic sealing of this implant system, which features
      an inner screw, renders it safe.

PMID- 24278951
TI  - Experience with bone morphogenetic protein-2 and interpositional grafting of
      edentulous maxillae: a comparison of Le Fort I downfracture to full-arch
      (horseshoe) segmental osteotomy done in conjunction with sinus floor grafting.
AB  - This paper is a retrospective report of the treatment of six patients with
      severely resorbed maxillae. Patients were treated, based on the amount of
      maxillary retrognathia, with either a Le Fort I downfracture or a "horseshoe"
      interpositional sandwich osteotomy, along with sinus elevation. Recombinant human
      bone morphogenetic protein-2 in an absorbable collagen sponge carrier was used
      for grafting in all patients, either alone or in combination with other grafting
      materials. Implants were placed and the patients were restored with fixed
      prostheses. Both grafting techniques are described, and the treated patients are
      presented. 

PMID- 24278952
TI  - Acceleration of wound healing with stem cell-derived growth factors.
AB  - PURPOSE: Recently, it has been revealed that bone marrow-derived mesenchymal stem
      cells (MSCs) accelerate the healing of skin wounds. Although the proliferative
      capacity of MSCs decreases with age, MSCs secrete many growth factors. The
      present study examined the effect of mesenchymal stem cell-conditioned medium
      (MSC-CM) on wound healing. MATERIALS AND METHODS: The wound-healing process was
      observed macroscopically and histologically using an excisional wound-splinting
      mouse model, and the expression level of hyaluronic acid related to the wound
      healing process was observed to evaluate the wound-healing effects of MSC, MSC
      CM, and control (phosphate-buffered saline). RESULTS: The MSC and MSC-CM
      treatments accelerated wound healing versus the control group. At 7 days after
      administration, epithelialization was accelerated, thick connective tissue had
      formed in the skin defect area, and the wound area was reduced in the MSC and MSC
      CM groups versus the control group. At 14 days, infiltration of inflammatory
      cells was decreased versus 7 days, and the wounds were closed in the MSC and MSC
      CM groups, while a portion of epithelium was observed in the control group. At 7
      and 14 days, the MSC and MSC-CM groups expressed significantly higher levels of
      hyaluronic acid versus the control group (P < .05). The expression level of
      hyaluronic acid was lower at 14 days than at 7 days in all three groups.
      CONCLUSIONS: Both the MSC and MSC-CM groups accelerated wound healing versus the
      control group to a similar degree. Accordingly, it is suggested that the MSC-CM
      contains growth factor derived from stem cells, is able to accelerate wound
      healing as well as stem cell transplantation, and may become a new therapeutic
      method for wound healing in the future.

PMID- 24278953
TI  - Zygomatic implant placement in conjunction with sinus bone grafting: the
      "extended sinus elevation technique." a case-cohort study.
AB  - PURPOSE: The zygomatic implant is mainly indicated for the rehabilitation of
      extremely atrophied maxillae when bone augmentation should be avoided. One
      drawback of zygomatic implants, which typically pass through the sinus, is
      initial or late bone resorption around the implant neck, which can result in
      oroantral communications followed by possible infection of the sinus. To decrease
      the risk of sinus infection, a modified technique was developed to preserve the
      integrity of the sinus membrane and to regenerate bone around zygomatic implants
      using an extended sinus grafting approach. MATERIALS AND METHODS: Patients with
      extremely atrophied maxillae were provided with one to four zygomatic implants in
      conjunction with sinus grafting, plus conventional auxiliary implants, for
      immediate support of a provisional full-arch maxillary prosthesis. Definitive
      prostheses were delivered at 6 months after implant placement. All patients
      underwent clinical and radiographic examinations at 6 months. RESULTS: Twenty-two
      zygomatic and 23 conventional auxiliary implants were placed in 10 patients. The
      overall 6-month implant survival rate was 90.9% for zygomatic implants and 100%
      for auxiliary implants placed in the anterior area. Only two minor technical
      complications were seen, and clinical indicators (including probing pocket depth,
      keratinized tissue, and plaque and bleeding indices) were good in all patients. A
      substantial gain of radiographic bone around the zygomatic implants was observed.
      CONCLUSION: The proposed technique led to successful prosthetic function for all
      patients. With the described technique, exposed implant threads within the
      maxillary antrum are eliminated and the potential for biologic complications is
      minimized.

PMID- 24278955
TI  - Cell-based regenerative approaches to the treatment of oral soft tissue defects.
AB  - Oral soft tissue plays an important role in the structure and function of the
      oral cavity by protecting against exogenous substances, pathogens, and mechanical
      stresses. Repair of oral soft tissue defects that arise as a result of disease,
      trauma, or congenital abnormalities is often accomplished via transplantation or
      transfer of autologous mucosal tissue. However, this method of treatment can be
      complicated by the relatively small amount of autologous mucosal tissue that is
      available, as well as by the morbidity that may be associated with the donor site
      and patient reluctance to have oral (eg, palatal) surgery. To circumvent these
      problems, clinicians have turned to the fields of tissue engineering and
      regenerative medicine to develop acellular and cellular strategies for
      regenerating oral soft tissue. This review focuses on the efficacy and safety of
      cell-based investigational approaches to the regeneration of oral soft tissue. 

PMID- 24278956
TI  - Periodontal tissue engineering: defining the triad.
AB  - The idea that somatic stem cells are localized in periodontal ligament (PDL)
      tissues as PDL stem cells (PDLSCs) responsible for construction and
      reconstruction of the periodontium has been widely accepted. Many dental
      scientists have attempted to clarify the identity of these PDLSCs, but the number
      of PDLSCs localized in PDL tissues is too small to be routinely and conveniently
      analyzed. Therefore, researchers have been attempting to develop undifferentiated
      PDL cell lines by transducing them with genes that are suitable for
      immortalization. The present authors were the first to succeed in establishing
      two clonal human PDL stem/progenitor cell lines that possessed multipotency
      derived from PDL tissues and that expressed PDL-related molecules as well as
      neural crest- and embryonic stem-related markers. The differentiation stages of
      these cell lines appeared to vary based on their potential to differentiate into
      other lineage cells, their response to tissue regeneration-related cytokines, and
      their behavior when transplanted into immunodeficient rats. This review describes
      the phenotypes of these cell lines compared with reported PDLSCs or other MSCs
      and discusses contemporary circumstances related to PDL regenerative medicine.
      Differential analyses between these two clones will reveal the mechanism of
      differentiation of PDLSCs as well as their phenotypes. The results will also
      allow for the acquisition of a mass population of PDLSCs or other stem cells
      directed toward PDL-lineage cells and to develop an unmet treatment needed for
      construction and reconstruction of PDL tissues based on tissue engineering
      techniques. 

PMID- 24278957
TI  - Transcription factors for dental stem cell differentiation.
AB  - Dental stem cells are excellent for oral and craniofacial tissue engineering. A
      profound knowledge about molecular processes in dental stem cells is necessary to
      create treatment approaches in oral medicine. Transcription factors regulate gene
      expression and provide decisive information for cellular functions. In recent
      years, the authors have investigated transcriptomes in dental stem cells before
      and after osteogenic differentiation. The present paper reports on the potential
      role of selected transcription factors, including ZBTB16, TP53, and SP1, in
      dental stem cell differentiation. This review discusses putative molecular
      processes in dental stem cells and summarizes the current knowledge. 

PMID- 24278958
TI  - Somatic stem cell biology and periodontal regeneration.
AB  - Somatic stem cells have been acknowledged for their ability to differentiate into
      multiple cell types and their capacity for self-renewal. Some mesenchymal stem
      cells play a dominant role in the repair and reconstruction of periodontal
      tissues. Both dental-derived and some non-dental-derived mesenchymal stem cells
      possess the capacity for periodontal regeneration under certain conditions with
      induced differentiation, proliferation, cellular secretion, and their
      interactions. Stem cell-based tissue engineering technology promises to bring
      improvements to periodontal regeneration, biologic tooth repair, and
      bioengineered implants. The present review discusses the roles and values of
      various somatic stem cells in periodontal regeneration. 

PMID- 24278954
TI  - Temporomandibular disorders: a review of etiology, clinical management, and
      tissue engineering strategies.
AB  - Temporomandibular disorders (TMD) are a class of degenerative musculoskeletal
      conditions associated with morphologic and functional deformities that affect up
      to 25% of the population, but their etiology and progression are poorly
      understood and, as a result, treatment options are limited. In up to 70% of
      cases, TMD are accompanied by malpositioning of the temporomandibular joint (TMJ)
      disc, termed "internal derangement." Although the onset is not well
      characterized, correlations between internal derangement and osteoarthritic
      change have been identified. Because of the complex and unique nature of each TMD
      case, diagnosis requires patient-specific analysis accompanied by various
      diagnostic modalities. Likewise, treatment requires customized plans to address
      the specific characteristics of each patient's disease. In the mechanically
      demanding and biochemically active environment of the TMJ, therapeutic approaches
      that can restore joint functionality while responding to changes in the joint
      have become a necessity. One such approach, tissue engineering, which may be
      capable of integration and adaptation in the TMJ, carries significant potential
      for the development of repair and replacement tissues. The following review
      presents a synopsis of etiology, current treatment methods, and the future of
      tissue engineering for repairing and/or replacing diseased joint components,
      specifically the mandibular condyle and TMJ disc. An analysis of native tissue
      characterization to assist clinicians in identifying tissue engineering
      objectives and validation metrics for restoring healthy and functional structures
      of the TMJ is followed by a discussion of current trends in tissue engineering. 

PMID- 24278959
TI  - Occult peri-implant oroantral fistulae: posterior maxillary peri
      implantitis/sinusitis of zygomatic or dental implant origin. Treatment and
      prevention with bone morphogenetic protein-2/absorbable collagen sponge sinus
      grafting.
AB  - Sinus floor grafting with bone morphogenetic protein-2 for transsinus implant
      placement or as a salvage technique for sinus-involved peri-implantitis has been
      found to be successful. Transsinus implants for All-on-Four treatment, zygomatic
      implants including quad zygomatics, and infected transsinus implants underwent
      peri-implant grafting, which was found to seal off the sinus cavity from the oral
      cavity in an effort to prevent or treat sinusitis/peri-implantitis. 

PMID- 24278961
TI  - Can heat treatment procedures of pre-hydrolyzed silane replace hydrofluoric acid
      in the adhesion of resin cement to feldspathic ceramic?
AB  - PURPOSE: To evaluate the influence of heat treatment (HT) procedures of a pre
      hydrolyzed silane on bond strength of resin cement to a feldspathic ceramic.
      MATERIALS AND METHODS: Ceramic and composite blocks (N = 30) were divided into
      six groups (n = 5) and subjected to the following conditioning procedures: G1:
      9.6% hydrofluoric acid (HF) for 20 s + silane (RelyX Ceramic Primer, 3M ESPE) +
      resin cement (Panavia F2.0, Kuraray) (control); G2: HF (20 s) + silane + heat
      treatment in furnace (HTF) (100 degrees C, 2 min) + resin cement; G3: silane +
      HTF + resin cement; G4- HF (20 s) + silane + heat treatment with hot air (HTA)
      (50 +/- 5 degrees C for 1 min) + resin cement; G5: silane + HTA + resin cement;
      G6: silane + resin cement. The microtensile bond strength (MTBS) test was
      performed using a universal testing machine (1 mm/min). After debonding, the
      substrate and adherent surfaces were analyzed using a stereomicroscope and SEM to
      categorize the failure types. The data were statistically evaluated using one-way
      ANOVA and Tukey's test (5%). RESULTS: The control group (G1) showed no pre-test
      failures and presented significantly higher mean MTBS (16.01 +/- 1.12 MPa) than
      did other groups (2.63 +/- 1.05 to 12.55 +/- 1.52 MPa) (p = 0.0001). In the
      groups where HF was not used, HTF (G3: 12.55 +/- 1.52 MPa) showed significantly
      higher MTBS than did HTA (G5: 2.63 +/- 1.05 MPa) (p < 0.05). All failure types
      were mixed, ie, adhesive between the resin cement and ceramic accompanied by
      cohesive failure in the cement. CONCLUSION: Heat treatment procedures for the pre
      hydrolyzed silane either in a furnace or with the application of hot air cannot
      replace the use of HF gel for the adhesion of resin cement to feldspathic
      ceramic. Yet when mean bond strengths and incidence of pre-test failures are
      considered, furnace heat treatment delivered the second best results after the
      control group, being considerably better than hot air application.

PMID- 24278960
TI  - Effect of proline-rich synthetic peptide-coated titanium implants on bone healing
      in a rabbit model.
AB  - PURPOSE: Previous studies have demonstrated the capacity of a designed proline
      rich synthetic peptide to stimulate osteoblast differentiation and
      biomineralization in vitro. Therefore, the aim of the present study was to
      evaluate the osseointegration capacity of titanium (Ti) implants coated with
      these peptides in a rabbit model. MATERIALS AND METHODS: Four calibrated defects
      were prepared in the tibiae of three New Zealand rabbits, and the defects were
      randomized into a test group (peptide-modified machined Ti implant) and a control
      group (unmodified machined Ti implant). The performance in vivo was investigated
      after 4 weeks of implantation by real-time reverse transcriptase polymerase chain
      reaction of bone and inflammatory markers, microcomputed tomographic analysis of
      mineralized bone, and histologic examination. RESULTS: The peptides adsorbed in
      agglomerates on Ti and underwent a change in secondary structure upon adsorption,
      which induced an increase in surface wettability. Gene expression markers
      indicated that peptide-coated Ti implants had significantly decreased mRNA levels
      of tartrate-resistant acid phosphatase. A trend toward increased osteocalcin in
      the peri-implant bone tissue was also seen. Bone morphometric and histologic
      parameters did not show significant differences, although the peptide group
      showed a higher percentage of new bone histologically. CONCLUSIONS: Proline-rich
      peptides have potential as a biocompatible coating for promoting osseointegration
      of Ti implants by reducing bone resorption.

PMID- 24278962
TI  - Two-year follow-up of indirect posterior composite restorations of permanent
      teeth with excessive material loss in pediatric patients: a clinical study.
AB  - PURPOSE: To evaluate the clinical effectiveness of indirect composite
      restorations in permanent molars with excessive substance loss in pediatric
      patients who have undergone root canal treatments. MATERIALS AND METHODS: Molars
      of 29 pediatric patients underwent endodontic treatment. Sixteen molars were
      restored with an indirect posterior composite resin restoration and 13 molars
      were restored with a direct posterior composite resin restoration. The success of
      the restorations was evaluated for 2 years based on United States Public Health
      Service (USPHS) criteria, photographs after staining with basic fuchsine, and
      radiographic data. Data obtained from both groups were compared using the Mann
      Whitney U-test and Wilcoxon signed rank test. RESULTS: Evaluation of the clinical
      and radiographic data revealed no observable, statistically significant
      differences between the posterior and the indirect posterior composites (p >
      0.05). However, evaluation of photos taken of the patients' molars after staining
      with basic fuchsin revealed that direct posterior composites showed increased
      staining on the margins of the restorations after six months (p < 0.05).
      CONCLUSION: Considering the difficulties of restoring endodontically treated
      permanent teeth with excessive substance loss in child patients, indirect
      restorations may be seen as a better option.

PMID- 24278963
TI  - More on antidepressant drugs and infectious disease.
AB  - Three observational studies have suggested that depression and/or antidepressant
      drug use is associated with an increased risk of developing Clostridium difficile
      (C. difficile) infection (CDI), which is a clinically significant cause of
      diarrhea typically associated with the use of antibiotic drugs. Establishing
      causality from observed associations requires evidence from a variety of
      different scientific perspectives. The authors of these studies do not consider
      the complex relationship among depression, immune system function, and infectious
      disease, nor do they consider the antimicrobial or immune-modulating effects of
      antidepressant drugs. The methodology of these three CDI studies-and their
      various sources of bias-make it impossible to assess the causal validity of the
      association between CDI and depression or antidepressant drug exposure.

PMID- 24278965
TI  - Highlights from European Society of Cardiology Congress 2013.

PMID- 24278964
TI  - [The time is gone....].

PMID- 24278966
TI  - Reply to Brock: Renewed focus on the voice and social reward in children with
      autism.

PMID- 24278967
TI  - Reply to Hartig and Dormann: The true model myth.

PMID- 24278968
TI  - Evidence-based guideline: Treatment of parenchymal neurocysticercosis: report of
      the Guideline Development Subcommittee of the American Academy of Neurology.

PMID- 24278969
TI  - Evidence-based guideline: Treatment of parenchymal neurocysticercosis: report of
      the Guideline Development Subcommittee of the American Academy of Neurology.

PMID- 24278970
TI  - Author response.

PMID- 24278971
TI  - Addendum: Ospemifene (Osphena) for dyspareunia (Med Lett Drugs Ther 2013; 55:55).

PMID- 24278972
TI  - Sonographic diagnosis of pheochromocytoma in childhood and adolescence.

PMID- 24278973
TI  - Surveillance of the patients at high risk for developing hepatocellular carcinoma
      in Europe--between guidelines and reality.

PMID- 24278974
TI  - [Swiss Paraplegic Centre (SPC): In case of doubt about the quality of life --
      sometimes without professionals].

PMID- 24278975
TI  - [Jorg Giesecke: round-the-clock care by professionals imperative].

PMID- 24278976
TI  - [New to training, youth development and family and job in O and U].

PMID- 24278977
TI  - [Nonunion risk: OP - yes or no?].

PMID- 24278978
TI  - [Internal rotation is crucial!].

PMID- 24278979
TI  - Typhoon Haiyan: Philippines faces long road to recovery.

PMID- 24278980
TI  - In Bangladesh, funds dry up for arsenic mitigation research.

PMID- 24278981
TI  - Profile: France's ANRS turns 25.

PMID- 24278982
TI  - Authors' response.

PMID- 24278983
TI  - [Risk assessment - prognostic information for elucidation in clinical practice].

PMID- 24278984
TI  - [OP - glasses protect against radiation exposure].

PMID- 24278986
TI  - [The country needs young surgeons].

PMID- 24278987
TI  - [Randomized clinical trials in diabetic macular edema].
AB  - Diabetic macular edema (DME) is the main cause of visual acuity impairment in
      diabetic patients. The current standard therapy for patients with DME (focal/grid
      laser photocoagulation) usually does not improve impaired vision, and many
      patients continue to lose vision despite laser therapy. Vascular endothelial
      growth factor (VEGF) plays a key role in the pathogenesis of DME and is a major
      candidate as a therapeutic target for the treatment of DME. The advent of
      intravitreal anti-VEGF drugs, such a ranibizumab, has opened up a new era for the
      management of DME. The aim of this review is to summarize the evidence supporting
      the use of ranibizumab in clinical practice. The studies analyzed in this review
      are prospective, controlled, randomized clinical trials (RCT) that have focused
      on documenting the therapeutic effect of ranibizumab and its safety, providing
      encouraging results.

PMID- 24278988
TI  - [From scientific evidence to clinical practice: treatment protocols for diabetic
      macular edema].
AB  - Diabetic macular edema (DME) is now considered the leading cause of moderate
      vision loss in type 2 diabetic patients and has a high socioeconomic burden. In
      recent years, the therapeutic approach to this entity has changed. The role of
      laser treatment, considered the gold standard in clinical practice worldwide for
      more than 25 years, has been redefined. To understand current treatment
      algorithms, the pathophysiology of diabetic macular edema and the role played by
      vascular endothelial growth factor must be elucidated. Many clinical trials have
      emerged showing that intravitreal ranibizumab provides effective therapy with an
      acceptable safety profile. Based in these data, the European Medicines Agency has
      approved ranibizumab for the treatment of diabetic macular edema. This article
      aims to discuss new treatment options and the recently developed evidence-based
      algorithms.

PMID- 24278989
TI  - [BRAVO and CRUISE: ranibizumab for the treatment of macular edema secondary to
      retinal vein occlusion].
AB  - This article summarizes the results of the BRAVO and CRUISE trials, two
      randomized multicenter studies in patients with macular edema secondary to branch
      and central retinal vein occlusion, respectively. Randomization was 1:1:1 to 0.3
      mg of ranibizumab, 0.5 mg of ranibizumab or placebo. Monthly injections were
      administered for 6 months followed by a 6-month observation period in which
      treatment on an on-demand (PRN) basis was applied with 0.5 mg ranibizumab.
      Patients in the control group were also eligible for 0.5 mg ranibizumab treatment
      in the observation period. The results showed a significant anatomical and visual
      improvement in both treatment groups 7 days after the intravitreal injection. PRN
      treatment with monthly follow-up maintained the visual improvements achieved
      after the first 6 months of treatment. Patients in the control group who received
      PRN treatment after the first 6 months showed an anatomical improvement similar
      to that in the treatment groups but less visual improvement.

PMID- 24278990
TI  - [From scientific evidence to clinical practice: treatment regimens  for macular
      edema secondary to retinal vein occlusion].
AB  - Retinal vein occlusion (RVO) is the second most common cause of retinal vascular
      disease after diabetic retinopathy. Despite the existence of several possible
      treatment options, none was entirely satisfactory and many patients suffered
      irreversible visual loss. As a result of the BRAVO, CRUISE and GENEVA trials,
      ranibizumab and the intravitreal biodegradable implants of dexamethasone has
      recently been approved by the US Food and Drug Administration and the European
      Medicines Agency for the treatment of RVO secondary edema. In this paper we begin
      by describing the current treatment options for RVO associated macular edema and
      continue with the description of the treatment regimen with ranibizumab.

PMID- 24278991
TI  - Response to letter to the editor by Jeff Kelsey, Chemsage Ltd, on 2-butoxyethanol
      health effects.

PMID- 24278992
TI  - Effects of switching from efavirenz to raltegravir on endothelial function, bone
      mineral metabolism, inflammation, and renal function: a randomized, controlled
      trial.
AB  - We performed a randomized controlled trial in 30 HIV-infected participants to
      either continue tenofovir/emtricitabine/efavirenz (Continuation Group) or switch
      to tenofovir/emtricitabine/raltegravir (Switch Group) for 24 weeks. There were no
      significant differences in the changes in flow-mediated dilation, 25(OH) vitamin
      D, or parathyroid hormone levels. Total cholesterol, high sensitivity C-reactive
      protein, serum alkaline phosphatase, sCD14 levels, and renal function
      significantly declined in the Switch Group compared with the Continuation Group;
      however, sCD163 levels significantly increased in the Switch Group. These
      findings suggest that raltegravir is not inherently more beneficial to
      endothelial function compared with efavirenz but may impact renal function and
      monocyte activation.

PMID- 24279003
TI  - Abstracts of the Mid-Atlantic section of the American Urological Association 71st
      annual meeting.

PMID- 24278993
TI  - Rhinology fellowship training and its scholarly impact.
AB  - BACKGROUND: Previous examination of the impact of fellowship training on
      scholarly productivity among otolaryngologists found that head and neck surgeons
      and otologists had a higher mean h-index than fellowship-trained rhinologists.
      Because fellowship training in rhinology is a historically newer trend, the
      objectives of the present analysis were to further characterize research
      productivity among fellowship-trained academic rhinologists, including geographic
      and temporal trends, to gain insight into the future direction of scholarly
      pursuits within the field. METHODS: Fellowship-trained rhinologists in academic
      practices were identified from the American Rhinologic Society online listings
      and organized by academic rank, number of years in practice, location, and h
      index, as calculated using the Scopus database. RESULTS: Mean h-index rose with
      increasing years in practice after fellowship. The h-index, number of
      publications, and the E-factor (a newly described bibliometric) increased with
      successive academic rank. The E-factor for rhinologists in this current analysis
      was not statistically different from the values calculated for other
      otolaryngology subspecialties (p > 0.05). CONCLUSION: Fellowship-training in
      rhinology is a relatively recent development, with half of the academic
      rhinologists included in this analysis having completed fellowship training
      within the past 5 years. Scholarly productivity among academic rhinologists
      increases with academic seniority. As the current cohort of fellowship-trained
      rhinologists progress in their academic careers, previously described deficits in
      scholarly productivity relative to other subspecialties are expected to diminish.

PMID- 24279004
TI  - Abstracts of the 34th Annual Meeting of the American Urogynecologic Society
      (AUGS). October 16-19, 2013. Las Vegas, Nevada, USA.

PMID- 24279006
TI  - [Percutaneous retrograde cannulated screw fixation of acute stable scaphoid waist
      fracture by a transtrapezial approach].
AB  - OBJECTIVE: To explore the technique and effectiveness of percutaneous retrograde
      cannulated screw fixation for acute stable scaphoid waist fracture by a
      transtrapezial approach. METHODS: Between May 2010 and April 2012, 23 patients
      with acute stable scaphoid waist fracture were treated with percutaneous
      retrograde cannulated screw fixation by a transtrapezial approach. There were 18
      males and 5 females, aged 21-54 years with an average of 32 years. All fractures
      were caused by supporting with hands after falling. The locations were the left
      side in 10 cases and the right side in 13 cases. The major symptoms included the
      wrist swelling, tenderness at the anatomic snuffbox, and grip weakness. Two cases
      were accompanied by distal radius fractures. The time between injury and
      operation ranged from 1 to 5 days with an average of 3 days. RESULTS: All
      incisions healed by first intention. All the cases were followed up 4-26 months
      with an average of 10 months. All fractures healed 6-12 weeks postoperatively
      with an average of 8.2 weeks. The patients resumed normal life and work at 4-6
      weeks and at 2-4 months after operation, respectively. At last follow-up, all the
      wrists were free from the pain and the tenderness. The postoperative grip power
      ranged from 30 to 51 kg (mean, 37 kg). The active flexion-extension range of
      motion was 140-165 degrees with an average of 153.7 degrees. All patients were
      satisfied with the results of treatment. CONCLUSION: Percutaneous retrograde
      cannulated screw fixation by a transtrapezial approach is a simple, safe, and
      reliable method to treat acute stable scaphoid waist fracture. By this approach,
      it is easier to place the screws into the center of the long axis of scaphoid.

PMID- 24279005
TI  - Proceedings of the Indo-U.S. bilateral workshop on accelerating
      botanicals/biologics agent development research for cancer chemoprevention,
      treatment, and survival.
AB  - With the evolving evidence of the promise of botanicals/biologics for cancer
      chemoprevention and treatment, an Indo-U.S. collaborative Workshop focusing on
      "Accelerating Botanicals Agent Development Research for Cancer Chemoprevention
      and Treatment" was conducted at the Moffitt Cancer Center, 29-31 May 2012. Funded
      by the Indo-U.S. Science and Technology Forum, a joint initiative of Governments
      of India and the United States of America and the Moffitt Cancer Center, the
      overall goals of this workshop were to enhance the knowledge (agents, molecular
      targets, biomarkers, approaches, target populations, regulatory standards,
      priorities, resources) of a multinational, multidisciplinary team of researcher's
      to systematically accelerate the design, to conduct a successful clinical trials
      to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to
      achieve efficient translation of these discoveries into the standards for
      clinical practice that will ultimately impact cancer morbidity and mortality.
      Expert panelists were drawn from a diverse group of stakeholders, representing
      the leadership from the National Cancer Institute's Office of Cancer
      Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics
      (NExT), Food and Drug Administration, national scientific leadership from India,
      and a distinguished group of population, basic and clinical scientists from the
      two countries, including leaders in bioinformatics, social sciences, and
      biostatisticians. At the end of the workshop, we established four Indo-U.S.
      working research collaborative teams focused on identifying and prioritizing
      agents targeting four cancers that are of priority to both countries. Presented
      are some of the key proceedings and future goals discussed in the proceedings of
      this workshop.

PMID- 24279007
TI  - [Clinical research of ulnar styloid fracture complicated with wrist dorsal branch
      of ulnar nerve injury].
AB  - OBJECTIVE: To analyze the therapy and effectiveness of ulnar styloid fracture
      complicated with wrist dorsal branch of ulnar nerve injury. METHODS: Between
      October 2005 and October 2012, 16 cases of ulnar styloid fracture complicated
      with wrist dorsal branch of ulnar nerve injury were treated. There were 14 males
      and 2 females with an average age of 42 years (range, 22-58 years). Fracture was
      caused by traffic accident in 8 cases, by mechanical crush in 5 cases, and by
      falling in 3 cases. According to the anatomical features of the ulnar styloid and
      imaging findings, ulnar styloid fractures were classified as type I (ulnar
      styloid tip fracture) in 1 case and type II (ulnar styloid base fracture) in 15
      cases. The skin sensation of ulnar wrist was S0 in 5 cases, S1 in 1 case, S2 in 7
      cases, and S3 in 3 cases according to the criteria of the British Medical
      Research Council in 1954 for the sensory functions of the ulnar wrist. The time
      from injury to operation was 6-72 hours (mean, 18 hours). Fracture was treated by
      operative fixation, and nerve was repaired by epineurium neurolysis in 13 cases
      of nerve contusion and by sural nerve graft in 3 cases of complete nerve rupture.
      RESULTS: All incisions healed by first intention. Sixteen patients were followed
      up for an average time of 14 months (range, 6-24 months). The X-ray films showed
      that all of them achieved bone union at 4-10 weeks after operation (mean, 6
      weeks). No patient had complications such as ulnar wrist chronic pain and an
      inability to rotate. According to Green-O'Brien wrist scoring system, the results
      were excellent in 13 cases and good in 3 cases; according to the criteria of the
      British Medical Research Council in 1954 for the sensory functions of the ulnar
      wrist, the results were excellent in all cases, including 11 cases of S4 and 5
      cases of S3+. Two-point discrimination of the ulnar wrist was 5-9 mm (mean, 6.6
      mm). CONCLUSION: For patients with ulnar styloid fracture complicated with wrist
      dorsal branch of ulnar nerve injury, internal fixation and nerve repair should be
      performed. It can prevent ulnar wrist pain and promote sensory recovery.

PMID- 24279008
TI  - [Becker V-shaped lateral rotation osteotomy in total hip arthroplasty for Crowe
      type IV development dislocation of hip].
AB  - OBJECTIVE: To summarize the surgical technique and the effectiveness of Becker V
      shaped lateral rotation osteotomy in total hip arthroplasty (THA) for Crowe type
      IV development dislocation of the hip (DDH). METHODS: Between January 2000 and
      December 2009, 18 patients (22 hips) with Crowe type IV DDH underwent THA. There
      were 3 males and 15 females with an average age of 54 years (range, 41-75 years).
      The unilateral hip was involved in 14 cases and bilateral hips in 4 cases. All
      patients had over anteversion of the femoral neck, with the acetabular
      anteversion angle of (21.28 +/- 4.87) degrees, the femoral neck anteversion angle
      of (59.06 +/- 1.44) degrees, and combined anteversion angle of (80.33 +/- 1.55)
      degrees. All the patients had limb-length discrepancy, ranged from 1.0 to 3.5 cm
      (mean, 2.5 cm). Before operation, gluteus medius muscle strength was grade 2 in
      17 hips and grade 3 in 5 hips; severe or moderate claudication was observed in 13
      and 5 patients, respectively. Trendelenburg sign was positive in all patients.
      Preoperative Harris score was 30.00 +/- 6.32. Cementless prosthesis was used.
      Becker V-shaped lateral rotation osteotomy and subtrochanteric shortening with
      overlapping femoral resection were performed, and proximal femoral shaft
      splitting was performed on 21 hips having narrow bone marrow cavity. RESULTS: All
      the cases achieved primary healing of incision. No complication of anterior
      dislocation, deep infection, nerve traction injury, or femoral uncontrolled
      fracture occurred. All the cases were followed up 3-12 years (mean, 8 years).
      Postoperative X-ray films showed that the initial fixation result of femoral
      prosthesis was excellent in 18 hips and good in 4 hips. Bone healing of osteotomy
      stump was obtained at 3-6 months (mean, 5 months) after operation. Affected limb
      prolonged for 2.5-3.5 cm (mean, 3.0 cm) at 1 year after operation; limb-length
      discrepancy was 0.5-1.5 cm (mean, 1.0 cm). The gluteus medius muscle strength was
      restored to grade 4 in 5 hips and grade 5 in 17 hips. At last follow-up, 13
      patients had no claudication, and 5 patients had mild claudication; Trendelenburg
      sign was negative in 15 cases and was positive in 3 cases; the Harris score was
      significantly improved to 91.89 +/- 3.22; all showing significant difference when
      compared with preoperative ones (P < 0.05). At last follow-up, the acetabular
      anteversion angle, the femoral neck anteversion angle, and combined anteversion
      angle were (19.33 +/- 4.49), (13.33 +/- 5.70), and (32.67 +/- 5.35) degrees,
      respectively, all showing significant differences when compared with preoperative
      ones (P < 0.05). No aseptic loosening, osteolysis, or rediolucent line was found
      around the femoral component. No implant subsidence, stem varus, or revision
      occurred. CONCLUSION: Becker V-shaped lateral rotation osteotomy is a safe and
      predictable method to treat type Crowe type IV DDH.

PMID- 24279009
TI  - [Effectiveness of arthroscopic single-bundle posterior cruciate ligament
      reconstruction with remnant preservation and quadrupled hamstring tendons].
AB  - OBJECTIVE: To investigate the effectiveness of posterior cruciate ligament (PCL)
      reconstruction with remnant preservation and autogenous quadrupled hamstring
      tendons under arthroscopy. METHODS: Between October 2007 and August 2012, 32
      patients with PCL rupture were treated and followed up for more than 1 year.
      There were 24 males and 8 females, aged 20-53 years (mean, 35.6 years). The
      causes of injury included traffic accident injury in 21 cases, sports injury in 8
      cases, and falling injury from height in 3 cases. The disease duration ranged 1
      week to 2 years (median, 6.3 weeks). Nine patients had simple PCL rupture, 23
      patients complicated by ligament injury, including 10 cases of anterior cruciate
      ligament rupture, 11 cases of posterolateral corner injury, and 2 cases of
      posteromedial corner injury. Preoperative Lysholm score was 53.8 +/- 7.1.
      According to the International Knee Documentation Committee (IKDC) rating
      criteria, 10 cases were classified as grade C and 22 cases as grade D. PCL was
      reconstructed with autogenous quadrupled hamstring tendons, the tendons were
      fixed with EndoButton at the femoral side and with interference screw at the
      tibial side; floats of stump were cleaned up, and the structural stability and
      continuity ligament remnants were preserved. RESULTS: Primary healing was
      obtained in all incisions; no early complication occurred after operation. Thirty
      two patients were followed up 23.4 months on average (range, 12-36 months). All
      patients had no symptom of knee instability; the results of tibia sags sign,
      posterior drawer test, and Lachman test were negative. At last follow-up, the
      knee range of motion (ROM) returned to normal in all cases. The Lysholm score was
      92.3 +/- 2.0, showing significant difference when compared with preoperative
      score (t = -34.32, P = 0.00). According to the IKDC rating criteria, 26 cases
      were classified as grade A and 6 cases as grade B at last follow-up, showing
      significant difference when compared with preoperative grade (Z = -5.57, P =
      0.00). CONCLUSION: Arthroscopic single-bundle reconstruction of PCL with remnant
      preservation and quadrupled hamstring tendons has advantages of minimal trauma,
      simple operation, and good knee function recovery.

PMID- 24279010
TI  - [Effectiveness of arthroscopic treatment of anterior cruciate ligament tibial
      eminence avulsion fracture with non-absorbable suture fixation combined with mini
      plate].
AB  - OBJECTIVE: To evaluate the surgical techniques and effectiveness of arthroscopic
      treatment of anterior cruciate ligament (ACL) tibial eminence avulsion fracture
      with non-absorbable suture fixation combined with the miniplate. METHODS: Between
      January 2009 and March 2012, 32 patients with ACL tibial eminence avulsion
      fractures were treated. There were 18 males and 14 females, aged 12-40 years
      (mean, 17.5 years). The injury causes included traffic accident injury in 15
      cases, sport injury in 6 cases, and falling injury in 11 cases. The time from
      injury to operation ranged 7-18 days with an average of 9.5 days. Before
      operation, the results of Lachman test were all positive; the Lysholm score was
      52.13 +/- 4.22 and the International Knee Documentation Committee (IKDC) score
      was 44.82 +/- 2.44. According to Meyers-McKeever classification criteria, there
      were 12 cases of type II and 20 cases of type III. After arthroscopic poking
      reduction of fracture, tibial eminence avulsion fractures were fixed with the
      Ethibond non-absorbable sutures bypass figure-of-eight tibial tunnel combined
      with the metacarpal and phalangeal mini-plate. RESULTS: Primary healing was
      obtained in all incisions; no joint infection or skin necrosis occurred after
      operation. All patients were followed up with an average time of 22.4 months
      (range, 12-50 months). The patients showed negative Lachman test at 12 weeks
      after operation. Except 3 patients having knee extension limitation at last
      follow-up, the knee extension range of motion (ROM) was normal in the other
      patients; the knee flexion ROM was normal in all patients. The Lysholm score and
      IKDC score were significantly improved to 94.19 +/- 0.93 and 94.35 +/- 1.22 at
      last follow-up, showing significant differences when compared with preoperative
      values (t = 55.080, P = 0.000; t = 101.715, P = 0.000). CONCLUSION: The
      arthroscopic treatment of ACL tibial eminence avulsion fracture with Ethibond non
      absorbable suture fixation combined with mini-plate is an effective procedure
      with the advantages of minimal trauma, reliable fixation, and satisfactory
      recovery of the knee joint function.

PMID- 24279011
TI  - [Surgical treatment of Segond fracture and complications].
AB  - OBJECTIVE: To investigate the injury mechanism, clinical characteristics, and
      treatments of Segond fracture and complications. METHODS: Fifteen patients
      suffering from Segond fracture were treated between January 2007 and December
      2011. There were 10 males and 5 females, aged 16-50 years (mean, 31.8 years).
      Fracture was caused by traffic accident in 8 cases, by sports in 6 cases, and by
      bruise in 1 case. Before operation, the knee range of motion (ROM) was (36.60 +/-
      8.94) degrees; the Lysholm score was 32.27 +/- 3.73; and the International Knee
      Documentation Committee (IKDC) score was 42.34 +/- 4.97. The duration from injury
      to operation was 1-3 weeks with an average of 1.2 weeks. In 12 patients having
      associated anterior cruciate ligament (ACL) injury, arthroscopic reconstruction
      of ACL was performed with allogeneic anterior tibial tendon; in 2 patients having
      associated avulsion fracture of the intercondylar eminence of the tibia,
      arthroscopic fracture reduction and fixation with Orthocord wire were performed.
      In 8 patients having associated meniscus injury, meniscus suture and meniscectomy
      were performed in 3 and 5 patients, respectively. In 7 patients having associated
      collateral ligament injury, conservative treatment was given in 5 patients, and
      medial collateral ligament was repair in 2 patients. RESULTS: All incisions
      healed primarily without complications of infection and nerve or blood vessel
      injury. All the patient were followed up 12-16 months (mean, 14.3 months). At 12
      months after operation, the results of anterior drawer test, Lachman test, and
      lateral stress test were all negative. The knee ROM was (129.27 +/- 5.89)
      degrees, the IKDC score and Lysholm score were significantly increased to 89.45
      +/- 3.05 and 87.87 +/- 4.12 at 12 months after operation; all showing significant
      differences when compared with preoperative values (P < 0.05). CONCLUSION: Segond
      fracture is often combined with ACL, collateral ligament, and meniscus injuries,
      and the evidence of Segond fracture can strongly suggests the knee injury.
      Personalized treatment should be chosen according to complications.

PMID- 24279012
TI  - [Cannulated lag screw combined with lateral supporting plate for treatment of
      Hoffa fracture of Letenneur type I and type III].
AB  - OBJECTIVE: To investigate the effectiveness of cannulated lag screws combined
      with lateral supporting plates in the treatment of Hoffa fracture of Letenneur
      type I and type III. METHODS: Between May 2004 and April 2011, 11 patients with
      Hoffa fracture of Letenneur type I and type III were treated, including 6 males
      and 5 females with an average age of 36 years (range, 25-47 years). Factures were
      caused by traffic accident in 8 cases, by falling in 2 cases, and by the other in
      1 case. Fracture involved the left knee in 7 patients and the right knee in 4
      patients. According Letenneur's classification criteria, there were 7 type I
      fractures (6 lateral condyle fractures and 1 medial condyle fracture) and 4 type
      III fractures (3 lateral condyle fractures and 1 medial condyle fracture). Of 11
      fractures, 9 were fresh fractures and 2 were old fractures. Two 6.5 mm cannulated
      lag screws combined with lateral supporting plates were used to fix fractures by
      anterolateral or anteromedial incision. RESULTS: All incisions achieved primary
      healing with no early complication. All patients were followed up 12-26 months
      (mean, 15 months). X-ray films showed bone healing with an average healing time
      of 15 weeks (range, 10-18 weeks). No loosening or breaking of internal fixator
      was observed; the removal time of internal fixation was 9-15 months (mean, 12
      months). Accoding to Letenneur's functional assessment system, the results were
      excellent in 7 cases, good in 3 cases, and poor in 1 case at last follow-up.
      CONCLUSION: Cannulated lag screws combined with lateral supporting plates
      fixation is effective in treatment of Hoffa fracture of Letenneur type I and type
      III with a high union rate; anterolateral or anteromedial approach is the first
      choice for Hoffa fracture of type I and type III, especially for complicating by
      tibial plateau fracture or patella fracture.

PMID- 24279013
TI  - [Effectiveness of open reduction and internal fixation for Bosworth fracture].
AB  - OBJECTIVE: To explore the operative methods and effectiveness of open reduction
      and internal fixation for Bosworth fracture. METHODS: Between January 2005 and
      January 2012, 6 patients with Bosworth fractures caused by sprain were treated.
      There were 4 males and 2 females with an average age of 45.8 years (range, 24-73
      years). The time from injury to operation was 1-5 days (mean, 1.8 days). They
      were all closed fractures. According to Lauge-Hansen classification, 6 cases were
      classified as supination-external rotation type. The surgical treatments included
      open reduction and internal fixation by plate and screws. RESULTS: Infection
      occurred in 1 case and was cured after dressing changing; primary healing of
      incision was obtained in the other 5 cases. Six patients were followed up 15
      months on average (range, 12-24 months). The X-ray films showed fracture healing
      in all cases, with an average healing time of 9.5 weeks (range, 8-13 weeks). No
      loosening or breaking of internal fixator was observed during follow-up. The
      average full load-walking time was 12 weeks (range, 10-17 weeks). According to
      the ankle and hindfoot scale of American Orthopaedic Foot and Ankle Society
      (AOFAS), the average score was 89.5 (range, 81-94). CONCLUSION: For Bosworth
      fractures, good results can be achieved by early diagnosis, open reduction and
      internal fixation.

PMID- 24279014
TI  - [Preliminary effectiveness of I.T.S. locking plate for intra-articular calcaneal
      fractures].
AB  - OBJECTIVE: To summarize the preliminary effectiveness of I.T.S. locking plate for
      intra-articular calcaneal fractures. METHODS: Between July 2010 and July 2011, 18
      cases of intra-articular calcaneal fractures were treated. There were 10 males
      and 8 females with an average age of 46 years (range, 25-64 years). According to
      Sanders classification system, there were 3 cases of type II, 9 cases of type
      III, and 6 cases of type IV. The disease duration was 5-11 days (mean, 6 days).
      Open reduction and internal fixation with I.T.S. locking plate were performed via
      an L-shaped lateral extending incision. RESULTS: Superficial infection occurred
      in 1 case, and was cured after dressing changing; healing of incision by first
      intention was obtained in the other cases. Sixteen cases were followed up 14
      months on average (range, 12-18 months). X-ray films demonstrated the bone union
      in all cases with an average union time of 12 weeks (range, 10-14 weeks). No
      implant failure or irritation of peroneal tendon occurred during follow-up. X-ray
      films showed subtalar post-traumatic arthritis with mild pain in 1 case at 11
      months after operation, which was relieved by conservative treatment. At last
      follow-up, the Bohler angle was improved from (12.9 +/- 3.2) degrees
      preoperatively to (33.8 +/- 4.0) degrees postoperatively, showing significant
      difference (t = 22.78, P = 0.00); the Gissane angle was improved from (83.6 +/-
      6.4) degrees preoperatively to (119.9 +/- 8.5) degrees postoperatively, showing
      significant difference (t = 17.02, P = 0.00). The visual analogue scale (VAS)
      score was 1.3 +/- 1.2, and the ankle and hindfoot scale of American Orthopaedic
      Foot and Ankle Society (AOFAS) was 80.3 +/- 7.9 at last follow-up. CONCLUSION:
      Treatment of intra-articular calcaneal fracture with I.T.S. locking plate can
      obtain a stable fixation, which is a safe and effective method.

PMID- 24279015
TI  - [Treatment of post-traumatic chronic calcaneal osteomyelitis and soft tissue
      defect by using combined muscle and skin flaps of calf].
AB  - OBJECTIVE: To investigate the effectiveness of distally pedicled peroneus brevis
      muscle flaps and reverse sural neurovascular island flaps for post-traumatic
      chronic calcaneal osteomyelitis and soft tissue defects. METHODS: Between January
      2008 and January 2012, 9 patients suffering from post-traumatic chronic calcaneal
      osteomyelitis and soft tissue defects were treated, including 8 males and 1
      female with an average age of 33 years (range, 18-46 years). The left heel was
      involved in 4 cases, and right heel in 5 cases. Infection occurred after
      reduction and internal fixation of closed fractures of the calcaneus in 7 cases,
      and open calcaneal fracture and soft tissue defect in 2 cases. The disease
      duration was 2 months to 3 years (mean, 5 months). Purulent secretion, tissue
      necrosis, or sinus formation was observed in all wounds. The results of bacterial
      culture were positive. X-ray and CT examination showed uneven density of
      calcaneus and bone cavity or dead bone formation. After thorough debridement, the
      size of bone defect ranged from 3 cm x 3 cm x 3 cm to 6 cm x 4 cm x 3 cm; the
      size of soft tissue defect ranged from 7 cm x 3 cm to 12 cm x 7 cm. The distally
      pedicled peroneus brevis muscle flaps (11 cm x 3 cm-16 cm x 4 cm) were used for
      bone defect repair, and reverse sural neurovascular island flaps (8 cm x 4 cm-14
      cm x 8 cm) for soft tissue defect. The donor site was directly sutured in 6 cases
      and repaired by skin graft in 3 cases. RESULTS: After operation, reverse sural
      neurovascular island flaps survived in 9 cases, and all wounds healed by first
      intention. No necrosis or liquefaction of distally pedicled peroneus brevis
      muscle flaps was observed. Incision at donor site healed by first intention, and
      skin grafts at donor site survived. All cases were followed up 6-24 months (mean,
      13.5 months). The flaps had good texture. No recurrence of osteomyelitis was
      observed. Basic weight-bearing walking function was restorated. No obvious
      calcaneal collapse happened. CONCLUSION: The distally pedicled peroneus brevis
      muscle flap combined with reverse sural neurovascular island flap is one of the
      effective methods to treat post-traumatic chronic calcaneal osteomyelitis with
      soft tissue defect, with the advantages of simple operation and good blood
      supply.

PMID- 24279016
TI  - [Validation study on precision of digitized custom-made radial head prosthesis by
      three-dimensional visualization of virtual surgery].
AB  - OBJECTIVE: To study digitize design of custom-made radial head prosthesis and to
      verify its matching precision by the surgery of preoperative three-dimensional (3
      D) virtual replacement. METHODS: Six healthy adult volunteers (3 males and 3
      females, aged 25-55 years with an average of 33 years) received slice scan of
      bilateral elbow by Speed Light 16-slice spiral CT. The CT Dicom data were
      imported into Mimics 10.0 software individually for 3-D reconstruction image, and
      the left proximal radial 3-D image was extracted, the mirror of the image was
      generated and it was split into 2 pieces: the head and the neck. The internal
      diameter and the length of the radial neck were obtained by Mimics 10.0 software
      measurement tools. In Geomagic Studio 12 software, the radial head was simulated
      to cover the cartilage surface (1 mm thickness) and generated to an entity. In UG
      NX 8.0 software, the stem of prosthesis was designed according to the parameters
      above and assembled head entity. Each custom-made prosthesis was performed and
      verified its matching precision by the surgery of preoperative 3-D virtual
      replacement. RESULTS: Comparing the morphology of 6 digitize custom-made
      prostheses with ipsilateral radial heads by the 3-D virtual surgery, the error
      was less than 1 mm. The radial head prosthesis design on basis of the
      contralateral anatomy was verified excellent matching. CONCLUSION: The 3-D
      virtual surgery test and the digitized custom-made radial head prosthesis will be
      available for clinical accurate replacement.

PMID- 24279017
TI  - [Rotator cuff repair with decellularized tendon slices for enhancing tendon-bone
      healing in rabbits].
AB  - OBJECTIVE: To investigate the effect of canine decellularized tendon slices
      (DTSs) on tendon-bone healing in repairing rotator cuff injury of rabbit.
      METHODS: Canine DTSs were prepared by repetitive freeze/thaw 5 times combined
      with nuclease processing for 12 hours from the adult Beagles Achilles tendons.
      Histological observation and cytocompatibility evaluation for the canine DTSs
      were performed in vitro. Twenty-four mature male New Zealand white rabbits,
      weighing 2.5-3.0 kg, were randomly selected. U-shaped defect of more than 50% of
      normal tendon in width and 8 mm in length was made in infraspinatus tendons of
      unilateral limb as the experimental group; the canine DTSs were used to repair
      defect, and the insertion of infraspinatus tendon on greater tuberosity of
      humerus was reconstructed in the experimental group. No treatment was done on the
      contralateral limb as the control group. At 4, 8, and 12 weeks after operation,
      the specimens were harvested for histological observation and biomechanical test.
      RESULTS: Histological examination showed that collagen fibers of canine DTSs were
      well preserved, without residual cells. The cytocompatibility examination showed
      that fibroblasts attached well to canine DTSs. Biomechanical test showed that the
      maximum load and stiffness increased significantly with time, and the maximum
      load and stiffness at 12 weeks were significantly higher than those at 4 and 8
      weeks (P < 0.05). The maximum load and stiffness of the experimental group at 4
      and 8 weeks were significantly lower than those of the control group (P < 0.05).
      The stiffness of the experimental group at 12 weeks was significantly lower than
      that of the control group (t = -5.679, P = 0.000), but no significant difference
      was found in the maximum load at 12 weeks between 2 groups (t = -0.969, P =
      0.361). Histological observation showed that the control group displayed a 4
      layer structure of the tendon-bone insertion. In the experimental group at 4
      weeks, the tendon-bone interface was filled with granulation tissue, and a small
      amount of Sharpey's fibers-like connected the tendon to bone; granulation tissue
      disappeared, and fibroblasts, Sharpey's fiber, new cartilage, and chondrocytes
      significantly increased with time; tendon-bone interface became mature, but the
      tide line was not observed between the unmineralized fibrocartilage and
      mineralized fibrocartilage. CONCLUSION: Canine DTSs prepared by repetitive
      freeze/thaw 5 times combined with nuclease processing for 12 hours, can enhance
      the healing of host tendon-bone and improve the biomechanical characteristics of
      the rabbit infraspinatus tendon.

PMID- 24279018
TI  - [Prevention and repair of patellar ligament injury in total knee arthroplasty].
AB  - OBJECTIVE: To review the progress in the prevention and repair of patellar
      ligament injury in total knee Recent literature about the prevention and repair
      of patellar ligament injury in total knee arthroplasty arthroplasty. METHODS: was
      reviewed and analyzed. RESULTS: Increased exposure can prevent the patellar
      ligament injury, and treatments of acute patellar ligament rupture can be
      obtained by simple repair, reconstruction with allograft materials or artificial
      materials, and auxiliary strengthening. CONCLUSION: Patellar ligament injury in
      total knee arthroplasty should not be ignored. Active prevention and repair of
      patellar ligament injury can obtain better function of knee joint.

PMID- 24279019
TI  - [Research progress of a disintegrin and metalloproteinase with thrombospondin
      motif 4 and 5 in osteoarthritis].
AB  - OBJECTIVE: To review the progress of a disintegrin and metalloproteinase with
      thrombospondin motif 4 (ADAMTS-4) and ADAMTS-5 in osteoarthritis. METHODS: Recent
      literature about the ADAMTS-4 and -5 in osteoarthritis was analyzed; the
      structure, function, inhibitors of the ADAMTS-4 and -5, and the relationship
      between the proteases and osteoarthritis were analyzed and summarized. RESULTS:
      ADAMTS-4 and -5 can reduce chondrocyte and extracellular matrix by degrading
      aggrecan and cartilage oligomeric matrix protein, which induced the pathogenesis
      of osteoarthritis. CONCLUSION: ADAMTS-4 and -5 have been demonstrated to play
      important roles in osteoarthritis. It can better guide treatment and prevention
      of osteoarthritis to further study related mechanism of ADAMTS-4 and -5, and to
      promote the establishment of a clinical drug targets.

PMID- 24279020
TI  - [Mid-term effectiveness of anterior decompression and fusion with nano
      hydroxyapatite/polyamide 66 cage in treatment of cervical spondylotic
      myelopathy].
AB  - OBJECTIVE: To assess the mid-term effectiveness of anterior decompression and
      fusion with nanohydroxyapatite/polyamide 66 (n-HA/PA66) cage in treatment of
      cervical spondylotic myelopathy. METHODS: A retrospective study was made on 48
      patients with cervical spondylotic myelopathy who underwent anterior
      decompression and fusion with n-HA/PA66 cage between August 2008 and January
      2010. There were 33 males and 15 females with an average age of 54.5 years
      (range, 42-72 years). The disease duration was 3-12 months (mean, 6 months). The
      affected segments included 35 cases of single segment (C3, 4 in 7, C4, 5 in 18,
      and C5, 6 in 10) and 13 cases of double segments (C3-5 in 7 and C46 in 6). Of 48
      patients, 28 was diagnosed as having intervertebral disc protrusion, 12 as having
      ossification of posterior longitudinal ligament, and 8 as having vertebral
      osteophyte; 35 patients underwent single segmental anterior corpectomy and
      fusion, and 13 patients underwent single segmental anterior discectomy and
      fusion. The pre- and post-operative radiographs (cervical anteroposterior and
      lateral X-ray films and three-dimensional CT scans) were taken to measure the
      segmental height and lordosis angle. Brantigan et al assessment standard and
      visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores
      were used to evaluate the graft fusion and the improvement of clinical symptoms,
      respectively. RESULTS: All patients were followed up for 46 months on average
      (range, 36-54 months). No cage breaking, displacement, or sliding was found. At
      last follow-up, 36 cases were rated as Brantigan grade E, 10 cases as grade D,
      and 2 cases as grade C; the fusion rate was 96%. Both segmental height and
      lordosis angle were corrected significantly at immediate and 6 months after
      operation and last follow-up than those before operation (P < 0.05), but no
      significant difference was found among different time points after operation (P >
      0.05). At last follow-up, the cage subsidence was (1.3 +/- 1.0) mm. The VAS and
      JOA scores at 6 months after operation and last follow-up were significantly
      improved when compared with preoperative scores (P < 0.05), and the scores at
      last follow-up were superior to ones at 6 months after operation (P < 0.05).
      CONCLUSION: The mid-term effectiveness of anterior decompression and fusion with
      the n-HA/PA66 cage in patients with cervical spondylotic myelopathy is
      satisfactory because it can effectively restore and maintain segmental height and
      lordosis angle and promote osseous fusion.

PMID- 24279021
TI  - [Percutaneous anterior odontoid and transarticular screw fixation for type II
      odontoid fractures in elderly patients].
AB  - OBJECTIVE: To retrospectively analyze the effectiveness of percutaneous anterior
      odontoid and transarticular screw fixation for type II odontoid fracture treated
      in the elderly patients. METHODS: Between October 2009 and March 2012, 5 patients
      with odontoid fracture were treated with anterior triple screws fixation. There
      were 4 males and 1 female with an average age of 69.4 years (range, 65-74 years).
      Fracture was caused by falling injury from height in all cases. The average time
      between injury and operation was 6.8 days (range, 3-12 days). According to
      Anderson-D'Alonzo classification system, all 5 cases were classified as type II
      odontoid fractures; 1 case accompanied by anterior arch fracture. Four cases were
      rated as grade E and 1 case as grade D on the basis of Frankel classification
      system on nerve function evaluation. Percutaneous anterior odontoid and
      transarticular screw fixation were used in all cases. The operation time, intra
      operative blood loss, X-ray exposure time, and complications were recorded. The X
      ray films were taken to observe atlantoaxial stability and implant conditions.
      RESULTS: All patients were successfully complete the surgery, and no open
      operation was needed. The average operation time was 103.6 minutes (range, 93-114
      minutes). The average intra-operative blood loss was 5.6 mL (range, 3-10 mL). The
      average X-ray exposure time was 24.2 seconds (range, 17-32 seconds). Good
      reduction of atlantoaxial joint and primary healing of incision were obtained in
      5 patients. The average follow-up duration was 21.4 months (range, 12-35 months).
      Transient dysphagia occurred in 3 cases, and was cured after 5 days of expectant
      treatment. No major complications of carotid artery laceration, spinal cord
      injury, esophageal perforation, airway obstruction, and implant failure occurred.
      The X-ray films showed odontoid bony union, atlantoaxial stability and good
      position of screws. The average time of odontoid fracture union was 7 months
      (range, 5-10 months). Five patients had normal neurological function (Frankel
      grade E) at last follow-up. Three patients complained of neck discomfort and
      movement limitation and had normal daily activities without special therapy; the
      other 2 patients had no clinical symptom of discomfort. CONCLUSION: Percutaneous
      anterior odontoid and transarticular screw fixation is a safe and effective
      procedure for treatment of type II odontoid fractures in the elderly patients
      with minimally invasive surgical advantages.

PMID- 24279022
TI  - [Temporary ectopic implantation of amputated fingers and dorsalis pedis flaps for
      thumb reconstruction and skin defect repair of hands].
AB  - OBJECTIVE: To investigate the feasibility of temporary ectopic implantation of
      amputated fingers and dorsalis pedis flaps for thumb reconstruction and skin
      defect repair of the hand. METHODS: Between February 2006 and February 2012, 9
      patients with thumb amputation having no replanted condition were treated. There
      were 7 males and 2 females with an average age of 35 years (range, 20-45 years).
      The injury causes included explosive injury in 1 case, puncher injury in 1 case,
      stiring machine injury in 1 case, gear injury in 3 cases, and heavy pound injury
      in 3 cases. At 2-5 hours after injury, one-stage temporary ectopic implantation
      of amputated finger to foot was performed. After debridement, thumb defect was
      rated as degree III in 1 case, as degree IV in 3 cases, and as degree V in 5
      cases. When amputated fingers survived completely after 1-4 months, the amputated
      finger was replanted to its anatomic position, skin defect was repaired with
      dorsalis pedis flap. The area of skin defect ranged from 5 cm x 4 cm to 7 cm x 6
      cm. The area of flaps ranged from 6 cm x 5 cm to 8 cm x 7 cm. The donor site was
      repaired by the skin grafting. RESULTS: Arterial crisis occurred in 1 case after
      1 day of one-stage operation, and was cured after vascular exploration, and the
      amputated fingers survived in the others. The reconstructed thumbs and flaps
      survived after two-stage operation, and the skin graft at donor site survived.
      The patients were followed up 1-4 years (mean, 2.8 years). The reconstructed
      thumbs had good appearance and satisfactory opposition and finger-to-finger
      functions. According to the standard functional evaluation issued by Hand Surgery
      Association of Chinese Medical Association, the scores of survival fingers were
      73-91 (mean, 84); the results were excellent in 7 cases and good in 2 cases with
      an excellent and good rate of 100%. CONCLUSION: Temporary ectopic implantation of
      amputated finger to foot combined with dorsalis pedis flap can be used to
      reconstruct thumb and repair skin defect of the hand.

PMID- 24279023
TI  - [Submental island flap for repair of oral defects after radical resection of
      early-stage oral squamous cell carcinoma].
AB  - OBJECTIVE: To evaluate the effectiveness of the submental island flap for repair
      of oral defects after radical resection of early-stage oral squamous cell
      carcinoma (OSCC). METHODS: Between February 2010 and August 2011, 15 cases of
      early-stage OSCC were treated. Of 15 cases, 9 were male and 6 were female, aged
      from 48 to 71 years (mean, 63 years). The disease duration was 28-73 days (mean,
      35 days). Primary lesions included tongue (3 cases), buccal mucosa (8 cases),
      retromolar area (2 cases), and floor of mouth mucosa (2 cases). According to TNM
      classification of International Union Against Cancer (UICC, 2002) of oral cancer
      and oropharyngeal cancer, 2 cases were classified as T1N0M0 and 13 cases as
      T2N0M0. The results of the pathologic type were high differentiated squamous cell
      carcinoma in 11 cases and moderately differentiated squamous cell carcinoma in 4
      cases. The defect after resection of the lesion ranged from 5 cm x 3 cm to 8 cm x
      6 cm. All the cases underwent radical resection of the primary lesion and
      immediate reconstruction with submental island flap except 1 case with radial
      forearm free flap because of no definite venous drainage. The sizes of the
      submental island flap varied from 6 cm x 4 cm to 9 cm x 6 cm. RESULTS: Operation
      time ranged from 4 hours and 30 minutes to 7 hours and 10 minutes (mean, 5 hours
      and 53 minutes) in 14 cases undergoing repair with submental island flap. All the
      flaps survived completely in 13 cases except 1 case having superficial necrosis
      of the flap, which was cured after conservative treatment. Temporary marginal
      mandibular nerve palsy occurred in 1 case, and was cured after 3 months;
      submandibular effusion was observed in 3 cases, and was cured after expectant
      treatment. The follow-up period ranged from 8 to 15 months (mean, 10.5 months) in
      14 cases undergoing repair with submental island flap. Hair growth was seen on
      the flap and became sparse after 3 months in 2 male cases. The appearance of the
      face, opening mouth, swallowing, and speech were recovered well in 14 cases, and
      the donor site had no obvious scar. The follow-up period was 13 months in 1 case
      undergoing repair with radical free forearm flap, and the appearance and function
      were recovered well. No local recurrence was found during follow-up. CONCLUSION:
      The submental island flap has reliable blood supply, and could be harvested
      simply and rapidly. It can be used to repair oral defects in patients with early
      stage OSCC after radical resection.

PMID- 24279024
TI  - [Effectiveness of penile ventral scrotum cohesion place wedge cutting and
      improved Brisson technique for congenital buried penis].
AB  - OBJECTIVE: To investigate the effectiveness of the penile ventral scrotum
      cohesion place wedge cutting and improved Brisson technique for congenital buried
      penis. METHODS: Between March 2010 and June 2012, 68 boys with congenital buried
      penis were treated by the penile ventral scrotum cohesion place wedge cutting and
      improved Brisson technique, with a median age of 4 years and 10 months (range, 3
      months-13 years). Of 68 cases, 14 were classified as phimosis type, 14 as rope
      belt type, 20 as moderate type, and 20 as severe type. The body of penis
      developed well and had no deformity. After operation, complications were
      observed, and the effectiveness was evaluated by the designed questionnaire.
      RESULTS: Early postoperative complications occurred in 11 cases, including
      obvious adhesion of the outside wrapping mouth in 4 cases, scrotal skin bloat in
      5 cases, and distal foreskin necrosis in 2 cases; long-term complications
      occurred in 9 cases, including abdominal incision scar formation in 4 cases,
      wrapping mouth scar stricture in 3 cases, and short penis in 2 cases. Primary
      healing of incision was obtained in the other boys. Fifty-four cases were
      followed up 6-12 months (mean, 8 months). According to the designed
      questionnaire, satisfaction rate with the overall view in parents was 77.78%
      (42/54); the clinical improvement rate was 85.19% (46/54); exposure of the penis
      was satisfactory in parents of 50 cases; and the parents had no psychological
      burden of penis exposure in 46 cases, which were significantly improved when
      compared with preoperative ones (P < 0.05). The boys had no psychological burden
      of penis exposure in 29 cases (53.70%) after operation, showing no significant
      difference when compared with preoperative one (18 cases, 33.33%) (chi2 = 1.22, P
      = 0.31). CONCLUSION: Application of the penile ventral scrotum cohesion place
      wedge cutting and improved Brisson technique can effectively correct congenital
      buried penis.

PMID- 24279025
TI  - [Laparoscopic Y-shaped polypropylene mesh for uterine and vaginal vault
      prolapse].
AB  - OBJECTIVE: To investigate the effectiveness oflaparoscopic Y-shaped polypropylene
      mesh in the treatment of uterine and vaginal vault prolapse. METHODS: Between
      June 2010 and December 2012, 24 patients with uterine and vaginal vault prolapse
      were treated by laparoscopic pelvic reconstruction (vagina and uterus-sacral
      fixation) with Y-shaped polypropylene mesh. The age of patients was 35-60 years
      (mean, 48.6 years). The disease duration was 2-8 years (mean, 5 years). According
      to the pelvic organ prolapse quatitative (POP-Q) classification by International
      Continence Society (ICS), 16 cases were classified as uterine prolapsed degree II
      and 8 cases as degree III; 15 cases were classified as vaginal prolapse degree I,
      7 cases as degree II, and 2 cases as degree III. All patients received
      postoperative follow-up regularly. Subjective evaluation was done based on
      prolapse quality of life questionnaire (P-QOL), and objective evaluation based on
      POP-Q classification. RESULTS: All the patients were operated successfully. The
      operation time was 22-68 minutes (mean, 33 minutes); the blood loss was 30-80 mL
      (mean, 51 mL); the indwelling urethral catheter remain was 3-7 days (mean, 4
      days); and the hospitalization days were 4-9 days (mean, 6.8 days). Twenty-four
      patients were followed up 3-12 months (mean, 9 months), of whom, 2 were followed
      up less than 6 months. All patients had normal urination after withdrawal of
      urethral catheter, and the residual urine volume was in normal range. No patients
      had mesh erosion and discomfort during sex, vaginal and anal bearing down. The P
      QOL scores at 3, 6, and 12 months after operation were significantly improved
      when compared with the preoperative value (P < 0.05); but there was no
      significant difference among 3, 6, and 12 months after operation (P > 0.05). The
      postoperative POP-Q classification was degree 0 in 19 cases and degree I in 3
      cases, and the objective cure rate was 91.7%. No recurrence was found during
      followup. CONCLUSION: Laparoscopic Y-shaped polypropylene mesh for treatment of
      uterine and vaginal vault prolapse is a safe and effective method, especially
      applicable to preserve the uterus, and higher requirements of sexual life of
      patients.

PMID- 24279026
TI  - [Experimental study on radiofrequency ablation technology for treatment of
      infected wounds in minipigs].
AB  - OBJECTIVE: To observe the effect of radiofrequency ablation technology for the
      treatment of infected wounds in minipigs. METHODS: Infected wounds of full
      thickness skin defects (about 6.15 cm2/wound) were prepared in 8 6-month-old
      minipigs (weighing, 30-35 kg) using the method of Davis et al. The 160 wounds
      were randomly divided into 4 groups (n = 40). Infected wounds were debrided with
      the radiofrequency ablation technology in group A, with the electric knife in
      group B, and with the scalpel in group C; no treatment was done in group D as a
      control. The healing rate, healing time, and tissue filling rate were observed;
      bacterial quantitative examination and histological examination were done at 0,
      2, 7, and 14 days after operation. RESULTS: All infected wounds were successfully
      established after 48 hours when Staphylococcus aureus dilution were inoculated.
      The wounds after radiofrequency ablation technology treatment were fresh and flat
      with slight bleeding; the healing time of group A was significantly shorter than
      that of groups B, C, and D (P < 0.05), and the healing rate of group A was
      significantly higher than that of groups B, C, and D at 7 and 14 days after
      operation (P < 0.05). The tissue filling rate of group A was significantly higher
      than that of groups B, C, and D at 2 days after operation (P < 0.05); the tissue
      filling rates of groups A, B, and C were significantly higher than that of group
      D at 7 and 14 days after operation (P < 0.05). At 0, 2, 7, and 14 days, there
      were significant differences in the bacterial count per gram tissue among 4
      groups (P < 0.05), the order from low to high was groups A, B, C, and D. The
      histological observation showed that the surface of wound was smooth in group A
      at 0 day, and group A was better than the other groups in wound healing; at 2
      days, some exudates were observed in 4 groups, but it was least in group A. There
      was inflammatory cell infiltration in various degrees in 4 groups at 7 and 14
      days; it was lightest in group A with thick epithelium and dense collagen
      bundles, followed by groups B and C, and it was severe in group D. CONCLUSION:
      The radiofrequency ablation technology can effectively remove the necrotic
      tissues of infected wounds, remarkably reduce the number of bacteria, improve the
      healing rate, and shorten the healing time of wounds.

PMID- 24279027
TI  - [Ovarian function reconstruction by orthotopic transplantation of novel
      vitrification cryopreserved ovaries in chemotherapy-induced ovary damage rat
      model].
AB  - OBJECTIVE: To investigate the effects of ovarian tissue cryopreservation by
      needle immersed vitrification (NIV) method and subsequently orthotopic
      transplantation on ovarian function reconstruction in chemotherapy-induced ovary
      damage rat model. METHODS: A total of 52 matured virginal female Wistar rats at
      age of 8-9 weeks housed in specific-pathogen-free facilities, weighing 250-300 g.
      Vaginal smears were obtained daily, 50 rats having at least 2 consecutive normal
      estrous cycles were included in the experiment. Ten rats were selected as donors
      randomly, and NIV method was used for cryopreserving ovarian tissues. The
      remaining 40 rats were divided into 3 groups according to different treatments:
      cyclophosphamide group (C group, n = 14), cyclophosphamide/transplantation group
      (C/T group, n = 12), and control group (NS group, n = 14). In C group and C/T
      group, the rats received peritoneal injection of cyclophosphamide every day for
      21 days to establish the chemotherapy-induced ovary damage models; and then the
      frozen-thawed ovarian tissues orthotopically transplanted into the left ovarian
      bursae in C/T group. The rats received peritoneal injections of 0.9% saline
      solution every day for 21 days in NS group. Estrous cycle recovery time, ovary
      weight, morphology change of ovarian tissues, and follicle count were compared
      among 3 groups. RESULTS: One rat died at 2 days after transplantation in C/T
      group; the other rats survived to the completion of the experiment. At 4 weeks
      after the end of injection, no significant difference in body weight was found
      among 3 groups (P > 0.05). The rats of NS group had regular estrous cycle, but
      cyclic changes in vaginal smears were observed in C group and C/T group during
      cyclophosphamide treatment. The median estrous cycle recovery was 9 days (95%CI:
      7.9-10.1 days) in C group, and was 6 days (95% CI: 4.9-7.1 days) in C/T group,
      showing significant difference (chi2 = 6.571, P = 0.010). The ovarian weight
      showed an obvious downtrend in C group at 4 weeks after cyclophosphamide
      treatment, and an upward trend was observed in C/T group. The ovarian grafts
      survived and grew well in C/T group. Primordium follicles and primary follicles
      in C/T group and NS group were significantly more than those in C group (P <
      0.05), but no significant difference was found between NS group and C/T group (P
      > 0.05). There was no significant difference in secondary follicles and antral
      follicles among the 3 groups (P > 0.05). CONCLUSION: The method of ovarian tissue
      cryopreservation by NIV and subsequently orthotopic transplantation can
      significantly shorten the estrous cycle recovery time in chemotherapy-induced
      ovary damage rat model. Ovarian grafts grow well, follicle count is similar to
      normal level. So it has the potential ability of ovarian endocrine and fertility
      reconstruction after chemotherapy.

PMID- 24279028
TI  - [Micro RNA-451 promoting osteogenesis of mesenchymal stem cells by targeting
      regulatory calcium binding protein 39].
AB  - OBJECTIVE: To investigate the role of micro RNA-451 (miRNA-451) in promoting the
      osteogenesis of mesenchymal stem cells (MSCs) by targeting regulatory calcium
      binding protein 39 (CAB39). METHODS: pMIR-report and pRL-TK vectors were selected
      to identify the relationship between miRNA-451 and CAB39 by using dual-luciferase
      reporter assay. pre-miRNA-451 (group A), anti-miRNA-451 (group C), pre-miRNA
      negative control (group B), and anti-miRNA negative control (group D) were
      transfected into the C3H10T1/2 cells, respectively. Then, the cells were
      collected after osteogenic induction for 7 and 14 days. At 7 and 14 days, the
      real-time fluorescent quantitative PCR and Western blot assays were performed to
      detect the related osteogenetic biomarkers [Runx2 and alkaline phosphatase (ALP)
      mRNA] and expressions of CAB39 protein. At 14 days, the extracellular calcium
      deposition during the osteogenesis of MSCs was tested by Alizarin red staining
      method. RESULTS: CAB39 was the target gene of miRNA-451. At 7 and 14 days after
      osteogenic induction, the mRNA expressions of Runx2 and ALP in group A were
      significantly higher than those in group B (P < 0.05), and the expressions in
      group C was significantly lower than those in group D (P < 0.05). Furthermore, at
      14 days after osteogenic induction, the protein expression of CAB39 in group A
      (0.55 +/- 0.05) was significantly lower than that in group B (1.00 +/- 0.07), and
      the protein expression in group C (1.21 +/- 0.05) was significantly higher than
      that in group D (1.00 +/- 0.04), all showing significant difference (P < 0.05).
      Finally, at 14 days after osteogenic induction, the extracellular calcium
      deposition in group A was obviously more than that in group B, and group C was
      downregulated when compared with group D. CONCLUSION: miRNA-451 can promote the
      osteogenesis process of MSCs by downregulating the CAB39.

PMID- 24279029
TI  - [Effects of mechanical stimulation on expression of autoantigens in myoblasts].
AB  - OBJECTIVE: To explore the effects of mechanical stimulation on the expression of
      autoantigens in myoblasts. METHODS: According to different processing methods,
      C2C12 cells were divided into the experimental group and control group; the
      experimental group was divided into 4 subgroups: 2-, 4-, and 6-day and 1-day
      stretch groups. In 2-, 4-, and 6-day stretch groups, mechanical loading was added
      on the C2C12 cells at a stretching frequency of 0.25 Hz and cellular deformation
      amplitude of 10%, 2 hours a day for 2, 4, and 6 days respectively by Flexercell
      5000 strain unit, and at a stretching frequency of 1 Hz and cellular deformation
      amplitude of 15% for 1 hour in 1-day stretch group. In the control group, the
      cells were routinely cultured for 1, 2, 4, and 6 days (1-, 2-, 4-, and 6-day
      control). The cells were observed by inverted phase contrast microscope. The cell
      proliferation was detected by flow cytometry; the expressions of autoantigens
      were detected by Western blot method, including the Ku/the catalytic subunit of
      DNA-dependent protein kinase (DNA-PKcs), U1-70 (A part of ATP-dependent DNA
      helicase II), histidyl tRNA synthetase (HRS), and Mi-2 (reconfigurable components
      deacetylase complexes of NuRD). RESULTS: The exfoliated cells were found in 1-day
      stretch group, but no exfoliated cell was seen in the control group for 1-day
      culture. The cells proliferated more obviously in 2-day stretch group than in the
      control group for 2-day culture; cell differentiation was found in 4-day stretch
      group, and cell fusion in 6-day stretch group, which were similar to those in the
      control group for 4- and 6-day culture. After single stretching, cell apoptosis
      was found in 1-day stretch group, showing no significant difference in the
      relative DNA proliferation index (DPI) when compared with DPI of control group
      for 1-day culture (t = 0.346, P = 0.747). After cyclic stretching, DPIs of 2- and
      4- day stretch groups were significantly increased when compared with those of
      the control group for 2- and 4-day culture (P < 0.05), but no significant
      difference was found between control group for 6-day culture and 6-day stretch
      group (t = 1.191, P = 0.303). Compared with the control group for 2-day culture,
      the relative protein expression of autoantigens (DNA-Pkcs, Mi-2, HRS, and U1-70)
      in 2-day stretch group decreased significantly (P < 0.05), but no significant
      difference was found between control group for 4-day culture and 4-day stretch
      group (P > 0.05). The relative protein expressions of autoantigens in 4-day
      stretch group significantly increased when compared with those of 2-day stretch
      group (P < 0.05), but the relative protein expressions of autoantigens in the
      control group for 4-day culture significantly decreased when compared with those
      of the control group for 2-day culture (P < 0.05). CONCLUSION: Short-term
      mechanical stimulation can inhibit the expressions of autoantigens in myoblasts,
      but with the time prolonging, cell differentiation and fusion and adaptation to
      mechanical stimulation would result in diminished inhibitory effect.

PMID- 24279030
TI  - [Biomechanical analysis and classification of lumbosacral spondylolisthesis].
AB  - OBJECTIVE: To review the research progress of the risk factors for slip
      progression and the pathogenesis of lumbosacral spondylolisthesis, and to discuss
      the value of Spinal Deformity Study Group (SDSG) classification system for
      lumbosacral spondylolisthesis. METHODS: Recent articles about the risk factors
      for slip progression and the pathogenesis of lumbosacral spondylolisthesis were
      reviewed and comprehensively analyzed with SDSG classification system of
      lumbosacral spondylolisthesis. RESULTS: Pelvic incidence (PI) is the key
      pathogenic factor oflumbosacral spondylolisthesis. The Meyerding grade of slip,
      PI, sacro-pelvic balance, and spino-pelvic balance not only are the fundamental
      risk factors of slip progression, but also are the key factors to determine how
      to treat and influence the prognosis. Therefore, compared with Wiltse, Marchetti
      Bartolozzi, and Mac-Thiong-Labelle classification systems oflumbosacral
      spondylolisthesis, SDSG classification based on these factors mentioned above,
      has better homogeneity between the subjects of subgroup, and better reliability,
      moreover, could better guide operative plan and judge the prognosis. CONCLUSION:
      It is suggested that the SDSG classification system should be the standard
      classification for lumbosacral spondylolisthesis for the clinical and research
      work.

PMID- 24279031
TI  - [Recent progress of small intestinal submucosa in application research of tissue
      repair and reconstruction].
AB  - OBJECTIVE: To review the recent progress of the small intestinal submucosa (SIS)
      in application research of tissue repair and reconstruction. METHODS: The
      domestic and international articles on the SIS were reviewed and summarized.
      RESULTS: As a natural extracellular matrix, SIS has outstanding biological
      advantages, such as good mechanical property, tissue compatibility, and lower
      immunogenicity. SIS has been used to repair and reconstruct various types of
      tissue defects in animal models and clinical application, especially in the
      treatment of hernia, urinary system disease, and refractory skin trauma. The
      development of the tissue engineering technology expands the field of SIS repair
      and reconstruction and promotes the intensive study of SIS. However, the long
      term effect of SIS in tissue repair and reconstruction still remains to be
      further observation, while the cell/SIS material construction by tissue
      engineering technology also needs more studies. CONCLUSION: SIS has a widely
      promising application future in the tissue repair and reconstruction.

PMID- 24279032
TI  - [Advances in osteogenic mechanism and osteogenic effects of bone morphogenetic
      protein 6].
AB  - OBJECTIVE: To review the osteogenic mechanism and osteogenic effects of bone
      morphogenetic protein 6 (BMP-6) so as to provide the basis for further research
      of BMP-6. METHODS: The related articles about the osteogenic mechanism and the
      osteogenic effects of BMP-6 in experimental animals were extensively summarized.
      RESULTS: BMP-6 from bone matrix can transduct the osteogenic signal to bone
      marrow mesenchymal stem cells (BMSCs) by means of Smad protein signal
      transduction pathway. And the BMSCs which received the signals will differentiate
      into osteoblasts and chondroblasts. Therefore, BMP-6 plays an important role in
      the development and maturation of bone and cartilage. In addition, BMP-6 has a
      close relation with bone diseases, such as fracture, osteoporosis, and bone
      tumor. CONCLUSION: The deep research of BMP-6 is expected to provide a new
      therapeutic approach for treating bone diseases of nonunion, osteoarthritis, and
      osteoporosis.

PMID- 24279033
TI  - Does the Keogh report impact on perioperative care?

PMID- 24279034
TI  - Vive le (evidence-based practice) revolution.

PMID- 24279035
TI  - Why are perioperative practitioners reluctant to publish?

PMID- 24279036
TI  - Podiatry: an illustration of surgery provided by allied health professionals.
AB  - As with the prescribing of medicines, the provision of surgery continues to
      evolve and this is particularly true in the delivery of foot surgery which, until
      the 1960s, in the United Kingdom was practiced exclusively by medically qualified
      surgeons. Over the last 40 years however podiatric surgery performed by
      podiatrists has become established as a viable, safe and cost effective
      alternative to traditional models of service provision.

PMID- 24279037
TI  - A novel glucose-insulin infusion maintains perioperative glycaemic control
      through multiple transitions of care.
AB  - To measure the efficacy of the Glucose-Insulin Infusion--Parkland Protocol
      (GIPPr) compared to subcutaneous (SC) insulin, blood glucose readings were
      reviewed in diabetic adults admitted for surgical intervention of a soft tissue
      or bone infection in Dallas, Texas. Hypoglycaemia occurred in 0.69% of readings
      in GIPPr-treated patients compared to 4.52% in SC-treated patients. The GIPPr
      maintained a higher proportion of blood glucose readings between 3.89-10 mmol/L
      compared to SC insulin (85.40% versus 50.68%).

PMID- 24279038
TI  - Enhanced recovery after surgery (ERAS): an orthopaedic perspective.
AB  - Enhanced recovery after surgery (ERAS) is a programme that aims to improve the
      care of elective surgical patients. Accelerated care pathways are delivered using
      a multidisciplinary approach, leading to reduced lengths of hospital stay,
      improved quality of treatment, and better outcomes. These programmes have gained
      considerable popularity in orthopaedics recently, however their widespread
      adoption remains to be seen. This article highlights the key evidence concerning
      ERAS in orthopaedic surgery.

PMID- 24279039
TI  - The issues surrounding social network sites and healthcare professionals.
AB  - This article discusses issues surrounding online social networking, and the
      implications of the use of these sites by healthcare professionals. The article
      provides guidance to healthcare professionals, as the increased use of sites like
      Facebook and Twitter have the potential to bring risks to healthcare. Use of
      these websites can be a very grey area, and boundaries need to be clearly set to
      ensure protection of service users and healthcare staff alike.

PMID- 24279040
TI  - Building on 'jack of all trades' skills.

PMID- 24279041
TI  - Where are the jobs? Asks disheartened new graduate.

PMID- 24279042
TI  - Rights of most vulnerable ignored.

PMID- 24279043
TI  - Fluoridated water adds protection.

PMID- 24279044
TI  - Embracing new technology.

PMID- 24279046
TI  - Migrant nurse articles 'insightful'.

PMID- 24279047
TI  - The president comments:.

PMID- 24279048
TI  - Breaking the silence on equal pay.

PMID- 24279049
TI  - Acceptance a key goal of therapy.

PMID- 24279050
TI  - Achieving six-hour stays in EDs.

PMID- 24279051
TI  - Supporting people with eating disorders.

PMID- 24279052
TI  - Antidepressants: their role in treating depression.

PMID- 24279053
TI  - Keeping a nursing watch in police cells.

PMID- 24279054
TI  - Reaching patients through music.

PMID- 24279055
TI  - Moving towards an outcomes health culture in mental.

PMID- 24279056
TI  - What does it mean to be a professional nurse?

PMID- 24279057
TI  - Future shock - a nurses warning.

PMID- 24279058
TI  - Learning to care for self first.

PMID- 24279059
TI  - New leaders for Runanga Tauira elected.

PMID- 24279060
TI  - Primary health care: becoming politically savy.

PMID- 24279061
TI  - Mental health: inspiring new nursing leaders.

PMID- 24279062
TI  - Update on women's health.

PMID- 24279063
TI  - Breaking barriers in women's health.

PMID- 24279064
TI  - For a true team approach, get interprofessional.

PMID- 24279065
TI  - Are you doing your part for the future?

PMID- 24279066
TI  - Common breast symptoms: when to refer to a breast surgeon.

PMID- 24279067
TI  - Health issues in lesbian patients: these women are at higher risk for certain
      infections and cancer.

PMID- 24279068
TI  - Incontinence in Women: evaluation in the primary care setting.

PMID- 24279069
TI  - Postpartum depression: low-income women have specific needs.

PMID- 24279070
TI  - Soaring salaries or another dip?

PMID- 24279071
TI  - The blogification of science.

PMID- 24279072
TI  - Others do it.

PMID- 24279073
TI  - Americans with Disabilities Act: understanding complexities and dentistry's role.

PMID- 24279074
TI  - Dentistry's intrinsic link to provision of services for persons with
      disabilities.
AB  - This article provides the dentist with a background on disabilities, education,
      practice and provision of services related to statutory and regulatory
      requirements, particularly the Americans with Disabilities Act anrid the
      California Fair Employment and Housing Act.

PMID- 24279075
TI  - Reducing the risk of an awDA lawsuit.
AB  - Improving access to your dental office now is cheaper than waiting to be sued.

PMID- 24279076
TI  - Is your dental office accessible to people with disabilities?
AB  - It has been estimated that more than 90 percent of the offices of health
      professionals in California have one or more accessibility issues, which commonly
      lead to lawsuits. Is your office amongthem?

PMID- 24279077
TI  - Disabled access claims: issues and liability.

PMID- 24279078
TI  - Disabled access resources at the California Dental Association.

PMID- 24279079
TI  - Who am I?

PMID- 24279080
TI  - The generosity of dentists.

PMID- 24279081
TI  - Patient payments and PCI security simplified.

PMID- 24279082
TI  - Oral health care during pregnancy.

PMID- 24279083
TI  - Member spotlight Dr. Jim D. Spurgeon, Norman.

PMID- 24279084
TI  - New dentist spotlight Dr. Lauran Spencer, Midwest City.

PMID- 24279085
TI  - Insurance for dentists and dental practices (from the basics to "I didn't know
      you could insure that!").

PMID- 24279086
TI  - Retirement planning.

PMID- 24279087
TI  - Five things every practice should do in today's economy.

PMID- 24279088
TI  - Making a difference one smile at a time.

PMID- 24279089
TI  - What are the ethical implications on having more than one fee schedule?

PMID- 24279090
TI  - Welcome to nurses' and midwives' wellbeing!

PMID- 24279091
TI  - Ageism and moral exclusion of older people.

PMID- 24279092
TI  - Privatisation: the threat to Australia's public hospitals.

PMID- 24279093
TI  - The Cochrane Collaboration: informing clinical decision making.

PMID- 24279094
TI  - Criteria led discharge.

PMID- 24279095
TI  - Pelvic pain: a diagnosis in itself.

PMID- 24279096
TI  - Oral health care during pregnancy.

PMID- 24279097
TI  - Midwives' prescribing: an Australian reality.

PMID- 24279099
TI  - Age is key to first-time mums' labour.

PMID- 24279098
TI  - Gestational diabetes mellitus (GDM) follow-up in the early postnatal period.

PMID- 24279100
TI  - Timing of motherhood is associated with poor mental health.

PMID- 24279101
TI  - Cervical screening for women with severe mental illness.

PMID- 24279102
TI  - "Expecting and Connecting" antenatal care group on the sunshine coast.

PMID- 24279103
TI  - Words...how what we say impacts.

PMID- 24279104
TI  - Women with substance use under-screened for pap smears.

PMID- 24279106
TI  - Shiatsu for women's health.

PMID- 24279105
TI  - A bystander or a father: men's experiences of birth trauma.

PMID- 24279107
TI  - Learning package on emergency contraception: a women's health nurse initiative.

PMID- 24279108
TI  - To measure pain and then let pain speak for itself: the role of elicited and non
      elicited verbal pain language in pain assessment across cultures.

PMID- 24279109
TI  - If it quacks like a duck...

PMID- 24279110
TI  - Good health begins with us.

PMID- 24279111
TI  - 2013 Sanford scholars day abstracts.

PMID- 24279112
TI  - Cardiovascular disease and bridging the diagnostic gap.
AB  - Cardiovascular disease (CVD) is now the leading cause of death worldwide. It
      continues to be on the rise and has become a true pandemic that has no respect to
      borders.' Coronary artery disease (CAD) is the most common type of CVD. It
      continues to be the leading cause of mortality both in men and women in the U.S.'
      Approximately every 25 seconds, an American will suffer an acute coronary
      syndrome, and approximately every minute someone will die of one. Risk
      stratification and early disease detection continue to be the bedrock of most
      preventative strategies. Risk assessment tools like Framingham Heart Score (FHS
      used in the U.S.), prospective cardiovascular monster (PROCAM used in Germany),
      or systemic coronary risk evaluation (SCORE used in Europe) are among the common
      and widely available estimators of a multi-factorial absolute risk of developing
      CVD.6 Recently, coronary artery calcium (CAC) has emerged as a non-invasive
      modality that might improve prediction of future cardiovascular events. We have
      conducted a comprehensive review of CVD risk factors, risk assessment and
      screening tools being applied to aid in early detection of CVD. As we work on
      bridging the diagnostic gap of the leading cause of mortality across the globe,
      utility of accurate and sensitive risk assessment and screening tools for early
      CVD detection is vital. This will aid in our goal of early detection, modifying
      risk factors and prevention of CVD incidence.

PMID- 24279113
TI  - Hospital-to-Home: a hospital readmission reduction program for congestive heart
      failure.
AB  - OBJECTIVE: To decrease the 30-day readmission rate following hospital stay for
      congestive heart failure, which in the United States approaches 30 percent
      nationally. In addition to indicating possible suboptimal care of patients with
      this condition, there are significant economic considerations. DESIGN:
      Prospective, non-randomized, two-center pilot project. SETTING: General hospital
      and cardiac specialty hospital, both located in a community of 150,000 population
      in predominantly rural South Dakota. PARTICIPANTS: All patients admitted between
      June 7, 2010 and June 6, 2011 with a diagnosis of congestive heart failure.
      INTERVENTION: An intensive transitions of care program was implemented to ensure
      adequate self-management training of patients and appropriate out-patient follow
      up and monitoring of the patient by the health care system. MAIN OUTCOME MEASURE:
      30-day all-cause readmissions. RESULTS: A statistically significant 42 percent
      relative reduction in 30-day readmission rate was documented for those patients
      participating in the pilot program. This represented a net economic savings, even
      accounting for the added cost of the intervention. CONCLUSIONS: An intensive
      transitions of care program decreases the 30-day readmission rate for patients
      with congestive heart failure in a non-urbanized Midwestern state like South
      Dakota.

PMID- 24279114
TI  - Management of hot flashes in menopausal women.

PMID- 24279115
TI  - Optimism 101: how to view investment loss as an opportunity.

PMID- 24279116
TI  - The risk management process.

PMID- 24279117
TI  - The flawed hero within us.

PMID- 24279118
TI  - Medication options for tobacco cessation.

PMID- 24279119
TI  - Our new enemy: sitting too much.

PMID- 24279120
TI  - Physician consortium for performance improvement: a collaborative for quality.

PMID- 24279121
TI  - Rurality and participation in mass preventive health services: a nationwide
      descriptive study.
AB  - People's engagement in community activities is reportedly stronger in rural areas
      than in urban areas. However, it is unknown whether this affects the health
      seeking behaviour of residents in rural communities. We examined whether the
      rurality-related index of a community was associated with the participation rate
      of residents in community-based preventive health services. Based on the national
      census data on all the 1816 municipalities in Japan in 2007, the correlation was
      evaluated between the participation rate in cancer screening (stomach cancer,
      colorectal cancer) or influenza vaccination programmes among those older than 65,
      and each of the municipality-level variables. The correlations were examined by
      simple correlation and multiple regression analyses. The correlations were also
      evaluated between voting rate (a parameter of people's engagement in community
      activities) and each municipality-level variable with multiple regression
      analysis. Simple correlation analysis showed that the population density was
      negatively correlated with the participation rate of all (stomach cancer,
      colorectal cancer, and influenza) preventive programmes (r = -0.367, -0.171 and 
      0.188, respectively; each p < 0.001). The significant correlations were
      maintained even after adjustment for other socioeconomic factors in multiple
      regression analysis in stomach cancer screening and influenza vaccination (beta =
      -0.279 and -0.133, respectively: each p < 0.05). Population density was
      negatively correlated with voting rate (beta = -0.488: p < 0.001). Residents in
      rural communities were more likely to participate in community-based mass
      preventive services and were more actively engaged in political activities than
      their urban counterparts. These results suggest that rural residents have a
      stronger sense of community, and this could potentially facilitate residents'
      engagement in mass preventive services.

PMID- 24279123
TI  - Diagnostic capability of gadoxetate disodium-enhanced liver MRI for diagnosis of
      hepatocellular carcinoma: comparison with multi-detector CT.
AB  - The purpose of this study was to evaluate the diagnostic capability of gadoxetate
      disodium (Gd-EOB)-MRI for the detection of hepatocellular carcinoma (HCC)
      compared with multidetector CT (MDCT). Fifty patients with 57 surgically proven
      HCCs who underwent Gd-EOB-MRI and MDCT from March 2008 to June 2011 were
      evaluated. Two observers evaluated MR and CT on a lesion-by-lesion basis. We
      analyzed sensitivity by grading on a 5-point scale, the degree of arterial
      enhancement and the differences in histological grades in the diffusion-weighted
      images (DWI). The results showed that the sensitivity of Gd-EOB-MRI was higher
      than that of MDCT especially for HCCs that were 1 cm in diameter or smaller. The
      hepatobiliary phase was useful for the detecting of small HCC. We had few cases
      in which it was difficult to judge HCC in the arterial enhancement between MRI
      and MDCT. In the diffusion-weighted image, well differentiated HCC tended to show
      a low signal intensity, and poorly differentiated HCC tended to show a high
      signal intensity. In moderately differentiated HCC's, the mean diameter of the
      high signal intensity group was larger than that of the low signal intensity
      group (24.5 mm vs. 15.8 mm). In conclusion, Gd-EOB-MRI tended to show higher
      sensitivity compared to MDCT in the detection of HCC.

PMID- 24279122
TI  - Changes in bone mineral density and metabolism in women: evaluation of bodily
      characteristics, bone metabolic markers and bone mineral density.
AB  - The relationship of bone mineral density (BMD) and bone metabolic markers in
      women is an interesting field of research. In this study, we aimed to clarify the
      relationship of body weight, bone metabolic markers and BMD. The subjects were 72
      women. The levels of serum bone-specific alkaline phosphatase (BAP), serum type I
      collagen-cross-linked peptide (s-NTx) and urinary deoxypyridinoline (u-DPD) were
      measured. The associations between dependent variables (BMD changes/1 or 4 years
      in the lumbar spine and femoral neck) and explanatory variables (body weight
      changes/1 or 4 years, the levels of BAP, s-NTx, u-DPD) were evaluated using
      multiple regression analysis. Changes in the lumbar spine BMD were significantly
      correlated with changes in height over a year, and those of the femoral neck were
      significantly correlated with changes in weight over a year. Changes in the
      lumbar spine BMD over 4 years were significantly correlated with age, BAP and the
      changes of weight over 4 years. Changes in the femoral neck BMD over 4 years were
      significantly correlated with the changes in weight for 4 years. These results
      suggest that BMD changes of different bones correlate with different explanatory
      variables and that, to predict BMD changes from bone metabolic markers in women,
      it is necessary to measure BAP levels.

PMID- 24279124
TI  - Induction of Timp1 in smooth muscle cells during development of abdominal aortic
      aneurysms.
AB  - Abdominal aortic aneurysm (AAA) is known to develop mainly by the increased
      diameter of aorta through metalloproteinases (MMPs). Although activities of MMPs
      are tightly regulated by the presence of tissue inhibitor of MMPs (TIMPs) and
      imbalances between MMPs and TIMPs may serve to fragility of arterial wall, little
      is known about TIMPs behavior in aneurysmal formation. Here, we utilized a murine
      experimental AAA model, and found that by immunohistochemical analysis, Timp1 as
      and Timp1 mRNA levels was also revealed in aortic tissue in AAA by RT-PCR. In
      cultured vascular smooth muscle cells (SMCs), Tumor Necrosis Factor (TNF)-alpha
      significantly activated both Mmp9 and Timp1 expression, and they were blocked by
      Jun kinase inhibitor (SP600125) in a dose-dependent manner. Interestingly, a
      proteasome inhibitor (MG132), which is known as an agent for inhibition of the
      nuclear factor-kappa B (NF-kappaB), significantly inhibited the TNF-alpha-induced
      expression of Timp1, whereas MG132, which also works as an activator of c-Jun/AP
      1 pathway, strongly increased Mmp9. Taken together, inflammatory cytokines,
      including TNF-alpha, may simultaneously induce MMPs and TIMPs for the remodeling
      of the medial layer, leading to the increased diameter of the aorta, the
      aneurysm.

PMID- 24279125
TI  - Enhancing students' cultural competence using cross-cultural experiential
      learning.
AB  - The purpose of this study was to explore undergraduate community health students'
      perceptions of their cultural competence. Little is known about students'
      cultural awareness, knowledge, and skills after their experience working with
      diverse cultural groups and language barriers. A cross-cultural experiential
      learning exercise was used as an educational approach. Reflective writing was
      used to elicit students' attitudes of the other culture and their coping skills.
      Three themes emerged as cultural awareness and knowledge, observation and
      learning, and cross-cultural communication. Results underscore the need for
      student academic preparation using cross-cultural educational approaches to
      enhance cultural competence.

PMID- 24279126
TI  - Taonga: grandchildren the treasures of grandparents.
AB  - Terns in a multi-ethnic sample of 125 depressed women seeking treatment for
      depression. Forty-six African American, 36 Caucasian Americans, and 43 Latina
      women were recruited and interviewed about their beliefs about their illness and
      their help-seeking. Results indicated that Latinas were significantly more likely
      than Caucasian Americans to believe that their illness was caused by traditional
      reasons (e.g., energy imbalance). African Americans were more likely to use
      spiritual resources (e.g., prayer, church) to deal with their problems than
      Caucasian Americans or Latinas. Caucasian Americans were more likely to use lay
      help (e.g., self care, friends and relatives) than Latinas. No ethnic differences
      in stigma for depressive illness were found. However, the belief in psychological
      or magico-religious-supernatural causes was associated with increased stigma, but
      medical and traditional causes were not. Traditional and magic-religious
      supernatural causes of illness were associated with using general health care,
      while psychological and medicinal causes were associated with seeking spiritual
      care. Additional research is needed to help us to understand how beliefs about
      the causes of illness and attitudes towards various sources of care interact to
      influence help-seeking practices.

PMID- 24279127
TI  - Diversity must start somewhere: the experience of one college of nursing.
AB  - The concept of diversity varies widely in its definition, conceptualization and
      connotations. Addressing issues of diversity within a college of nursing is
      necessary if the cultures of our academic units are to change and become more
      inclusive. The article provides an overview of how this CON began to address
      changing its culture to one of a more inclusive nature and across all groups
      represented within the college, not bound only by ethnicity and gender. The
      process described in this article may provide an example for others to follow.

PMID- 24279128
TI  - The effect of medical mathematics retention strategies in decreasing attrition
      rate among African American licensed practical nursing students in a community
      college.
AB  - BACKGROUND: This education evidence based study examined African American
      students entering the Practical Nursing program and the strategies of medical
      mathematics bridge and tutoring programs to reduce attrition. PURPOSE: To
      increase retention in the fundamentals of nursing courses, augmenting the program
      completion rate. DATA/OBSERVATIONS: Two groups of students (n = 105) participated
      for this one-year study over three semesters. Data revealed passing rates of 87%
      92% for the nursing course and 75%-92% on medical mathematics when consistently
      attending programs. The attrition rate plummeting to 8% -34% contrasting previous
      years 43%-65%. CONCLUSIONS: Retention intervention programs can have a positive
      impact on minority students' academic performance.

PMID- 24279129
TI  - Moving toward cultural competency: DREAMWork online summer program.
AB  - This article describes the origination and implementation of an online,
      interactive summer component of the Diversity Recruitment and Education to
      Advance Minorities in the Nursing Workforce Program (DREAMWork) at University of
      Tennessee at Chattanooga (UTC). The summer course was designed as a strategy to
      help prepare baccalaureate nursing students to provide both culturally sensitive
      and competent care through online learning. Sixteen baccalaureate nursing
      students participated in the four week online summer program. Course objectives
      were framed using Campinha-Bacote's (2002) model of cultural competence (Figure
      1). Analysis revealed at the end of the four week summer program, students were
      more comfortable discussing their own prejudices and biases and were left with a
      deeper appreciation of what it meant to provide culturally sensitive care. The
      results of this summer program suggest the need to expand the online course to
      allow DREAMWork pre-nursing students to address the issue of becoming culturally
      competent prior to admission into upper division nursing clinical courses. This
      project was supported by funds from the Division of Nursing (DN), Bureau of
      Health Professions (BHPr), Health Resources and Services Administration (HRSA),
      Department of Health and Human Services (DHHS) under grant # D19HP08214.

PMID- 24279130
TI  - An exploratory study of sexual assertiveness and characteristics of African
      American women in negotiating condom use at an HBCU.
AB  - The transmission of HIV/AIDS among African American women through heterosexual
      sex is an epidemic. Critical themes extracted from the HIV/AIDS sexual
      assertiveness literature revealed that: (a) sexual assertiveness is related to
      HIV risk, (b) sexual assertiveness is related to communication, and (c) women
      with low sexual assertiveness are at risk for HIV. This descriptive study sought
      to answer the following research question: What do young adult college attending
      African American women self-report about asking information about their partner's
      sexual history? The multifaceted model of HIV risk is the theoretical framework
      which guided this descriptive study. A basic tenet of the multifaceted model of
      HIV risk is that there is no single predictor of women's HIV risk behavior.
      Results revealed that 104 young adult college attending African American women
      who volunteered to attend a one day HIV prevention training overall scored high
      on a Sexual Assertive Scale on subscales of Information Communication, Refusal,
      and Pregnancy/STD Prevention Subscale, and scored in the medium range on the
      Initiation Subscales. The Information Communication and Pregnancy/ STD Prevention
      Subscale received the highest scores. More research is needed targeting diverse
      African American females with different socioeconomic status, various locations,
      and educated to determine their sexual assertiveness with partners which are
      essential in developing specific programs for diverse groups of African American
      females.

PMID- 24279131
TI  - Sexual communication needs of African American families in relation to faith
      based HIV prevention.
AB  - In this study, we examined the sexual communication needs of African-American
      parents and their adolescent children in relation to faith-based HIV prevention.
      Eight focus groups of 10 members each were conducted, four with parents and four
      with adolescents. The sessions were audiotaped and transcribed verbatim. Findings
      indicated that some African Americans are not knowledgeable about sexually
      transmitted infections. The sample members were not in agreement about when
      sexual communications should begin, yet the majority felt that the church was the
      best place to have these discussions. Healthcare professionals can use the
      findings from this study to assist faith-based organizations to strengthen the
      sexual communication skills of African-American families.

PMID- 24279132
TI  - [Red swollen helix, facial erythema a week later. Borrelia lymphocytoma].

PMID- 24279133
TI  - [The magic formula is: innovative ideas plus engagement].

PMID- 24279134
TI  - [Promotion of family physicians must be included in the coalition contract].

PMID- 24279135
TI  - [Empathy as wonder drug].

PMID- 24279136
TI  - ["The psychosocial competence of the physician is rewarded too little" (interview
      by Dr. med. Horst Gross)].

PMID- 24279137
TI  - [Edoxaban is safer than vitamin K antagonists].

PMID- 24279138
TI  - [Extreme endurance sport significantly increases longevity].

PMID- 24279139
TI  - [First sudden deafness, then myocardial infarct].

PMID- 24279140
TI  - [Many asthma patients turn to complementary medicine].

PMID- 24279141
TI  - [Sunglasses as pollen barrier].

PMID- 24279142
TI  - [Naturopathy consultation. Stress - burnout - depression: can herbs help here?].

PMID- 24279143
TI  - [Early replenishment of iron reserves!].

PMID- 24279144
TI  - [Abdominal pain in children: Parasites to blame?].

PMID- 24279145
TI  - [Vitamin D and atopic diseases].

PMID- 24279146
TI  - [A decline in cognition, when a psychosis is no longer treated?].

PMID- 24279147
TI  - [Which heart rate in atrial fibrillation?].

PMID- 24279148
TI  - [PET reveals the best antidepressant therapy].

PMID- 24279149
TI  - [Diabetes acts as BNP booster. ].

PMID- 24279150
TI  - [Emergencies in the daily general practice: exercise regularly].

PMID- 24279151
TI  - [Handling of emergencies within the daily general practice].

PMID- 24279152
TI  - [Foreign body aspiration in children].

PMID- 24279153
TI  - [Dyspnea].

PMID- 24279154
TI  - [ST-segment depressions-- are you familiar with them?].

PMID- 24279155
TI  - [Tapentadol - how does it work in chronic pain?].

PMID- 24279156
TI  - [Disorders of sexual function in the woman. She loves her partner - and dreams of
      other men].

PMID- 24279157
TI  - [Isolated systolic hypertension. Therapy or not?].

PMID- 24279158
TI  - [Ulcerating basal cell carcinoma--an important differential diagnosis for chronic
      wounds in the facial area].

PMID- 24279159
TI  - [Prevention of stroke in nonvalvular atrial fibrillation. Oral direct factor Xa
      inhibitor apixaban: positive experiences in general medical practice].

PMID- 24279160
TI  - Organisation of autonomic nervous structures in the large intestine of chinchilla
      (Chinchilla laniger Molina).
AB  - The organization of autonomic nerve structures in the large intestine of
      chinchilla was investigated using histochemical and immunocytochemical methods.
      The myenteric plexus formed network nodes of cholinergic neurocyte agglomerations
      connected with bundles of nerve fibres and localized between the circular and
      longitudinal layers of the smooth muscles. The highest density of myenteric
      plexus was observed in the rectum. The different densities of myenteric plexus in
      subsequent parts of the large intestine is connected with the disparate functions
      of this part of the gut. The submucous plexus was distributed at several levels
      of mucosa and was a more dispersed structure than the myenteric plexus.
      Characteristic varicose adrenergic fibres were observed within the myenteric and
      submucous plexus in different layers of the large intestine wall.

PMID- 24279161
TI  - In vitro response of human pathological hematopoietic cells to cladribine.
AB  - The influence of cladribine (2-chloro-2'-deoxyadenosine, CdA) on in vitro
      response of human acute lymphoblastic leukemia MOLT-4 cells, human histiocytic
      lymphoma U-937 cells, and human promyelocytic leukemia HL-60 cells, was
      determined using the MTT spectrophotometric and Beckman Coulter methods. Cell
      viability, cell volume and count were compared 24h and 48h after cladribine
      application at four concentrations--50 nM, 100 nM, 250 nM, and 500 nM. Different
      patterns of temporary changes in the viability, volume and count of pathological
      hematopoietic cells exposed to the action of CdA were found. The effects of CdA
      on MOLT-4, U-937, and HL-60 cells were dependent on the agent tested and its
      concentration, the time intervals after agent application, and the cell line
      used. The various in vitro cytotoxic activities of CdA against the three human
      pathological hematopoietic cell lines were shown.

PMID- 24279162
TI  - The use of primed in situ synthesis (PRINS) to analyze nucleolar organizer
      regions (NORs) and telomeric DNA sequences in the domestic chicken genome.
AB  - One of the most often analyzed avian genomes is the domestic chicken genome
      (Gallus domesticus) whose diploid number is 2n = 78. In the chicken karyotype,
      similarly to other birds, there is a group of microchromosomes for which the
      determination of morphology and banding pattern is impossible using classic
      cytogenetics methods. The aim of this study was to evaluate telomeric and rDNA
      repetitive sequences in the chicken genome by the PRINS technique as an
      alternative method to fluorescence in situ hybridization. This is the first
      report on the application of the PRINS method to locate these repetitive
      sequences in the chicken nuclei and metaphase chromosomes.

PMID- 24279163
TI  - Polymorphism of cytogenetic markers in wild and farm red fox (Vulpes vulpes)
      populations.
AB  - Analysis of the origin of domestic animals is of wide interest and has many
      practical applications in areas such as agriculture and evolutionary biology.
      Identification of an ancestor and comparison with the domesticated form allows
      for an analysis of genetic, physiological, morphological and behavioral effects
      of domestication. Because fox breeding has been an ongoing process for over a
      century, differences are expected between farm and wild populations at the
      chromosomal level. The aim of this work was to analyse polymorphisms at the
      chromosomal level in foxes raised on farms and those living in the wild. Blood
      samples and lung tissue served as the experimental material and were obtained
      after slaughter of 35 foxes, including 28 breeding animals and 7 wild animals.
      The classical cytogenetic method was used including AgNOR technique, as well as
      molecular methods such as fluorescence in situ hybridization (FISH), and primed
      in situ labeling (PRINS). Analysis of the number of B chromosomes showed the
      presence of polymorphisms in foxes from both studied populations, but there was
      no correlation between the number of B chromosomes and the origin and gender of
      particular animals. An analysis ofactive nucleolar organizers showed the presence
      of a large number of polymorphisms and a tendency towards reduction of the number
      of NORs in the captive-raised population.

PMID- 24279164
TI  - DNA methylation analysis of the gene CDKN2B in Gallus gallus (chicken).
AB  - Methylation is an epigenetic modification of DNA affecting gene expression
      without changing the structure of nucleotides. It plays a crucial role in the
      embryonic and post-embryonic development of living organisms. Methylation level
      is tissue and species-specific and changes with age. The study was aimed at
      identifying the methylation of the CDKN2B gene situated at locus bar in Polbar
      chickens on the 6th and 18th day of embryonic development using the MSP
      (methylation-specific PCR) method. Methylation was not detected in the promoter
      region of gene CDKN2B on the 6th and 18th day of embryonic development. As one of
      the five genes responsible for melanine activity in melanocytes and highly
      active, it can contribute to the production of this pigment. The present research
      broadens the current knowledge of the chicken epigenome and the mechanism of
      autosexing in birds.

PMID- 24279165
TI  - The evaluation of bovine SNP50 beadchip assay performance in Polish red cattle
      breed.
AB  - According to increasing interest in the use of high density SNP (single
      nucleotide polymorphism) genotyping assays for genome-wide genetic studies in
      farm animals, there is a need to assess the usefulness of currently available
      genomic tools for application in different breeds. The performance of the assays
      may differ between the breeds because of discrepancies in allele frequencies of
      the polymorphisms or differences in linkage disequilibrium patterns. In this
      study we attempted to test the performance of the Bovine SNP50 v2 genotyping
      assay (Illumina) for population genetic and other applications in the Polish Red
      cattle breed. We found that 37,977 of the 53,438 autosomal markers included in
      the assay give high quality genomic information and can be used for different
      applications concerning this breed. The remaining markers were denoted as "of
      limited use" or redundant because of their weak performance, deviation from Hardy
      Weinberg equilibrium, low minor allele frequency, high linkage disequilibrium
      with other neighboring markers or location on sex chromosomes.

PMID- 24279166
TI  - Cytogenetic analysis of Otiorhynchus bisulcatus (Fabricius, 1781) and
      O.(Zadrehus) atroapterus (De Geer, 1775) (Coleoptera, Curculionidae, Entiminae)
      using C bands, NORs, and DAPI/CMA3 staining.
AB  - The structure of the karyotypes of two Otiorhynchus species belonging to separate
      subgenera, viz. Otiorhynchus s.str. bisulcatus and O. (Zadrehus) atroapterus, is
      compared and described for the first time. Both species have the same chromosome
      number (2n = 22), sex chromosome system of an achiasmate parachute type (Xy(p)),
      symmetric karyotype with the prevalence of metacentrics, similar meiotic
      behaviour, localization of NORs and positive DAPI signals. The main differences
      involve the morphology of autosomes and the X chromosome in the C-banding pattern
      and DAPI/CMA3 signals as well as in the presence of additional B chromosomes.

PMID- 24279167
TI  - Rapid identification of Borrelia by high resolution melting analysis of the groEL
      gene.
AB  - This study examined the possibility of applying a new diagnostic method, high
      resolution analysis of DNA denaturation curve (high resolution melting - HRM),
      for identification of Borrelia species. DNA samples were obtained from Ixodes
      ricinus ticks collected from vegetation and removed from hunted roe deer. For
      differentiation of Borrelia species, the HRM protocol based on the analysis of
      the groEL gene was applied. A product characteristic for Borrelia was obtained in
      19/123 samples (15.4%). The studied isolates were classified as four species: B.
      garinii, B. valaisiana, B. afzelii and B. miyamotoi. Two separate groups of
      isolates within the B. afzelii species were also found. The results show that the
      groEL gene is useful for rapid differentiation of B. burgdorferi sensu lato with
      the HRM method from different extracts of DNA and it also allows precise
      differentiation of Borrelia species and strains. The HRM method shortened and
      simplified detection and differentiation of Borrelia species from different
      biological sources.

PMID- 24279168
TI  - A chromosomal analysis of twelve species of the subfamily Chrysomelinae
      (Coleoptera, Chrysomelidae).
AB  - Twelve species of chrysomelines, all but one from the Palaearctic region, have
      been cytogenetically analyzed, mostly through their male meiotic metaphases I.
      Ambrostoma superbum has 2n = 40 (Xy(p)), Chrysolina colasi, Oreina fairmairiana
      and the Neotropical Platyphora spectabilis have 2n = 24 (Xy(p)), Chrysolina
      gebleri 2n = 26 (XY(p)), Colaspidema barbarum 2n = 28 (Xy(p)), Crosita altaica
      and C. rugulosa 2n = 30 (Xy(p)), Phratora polaris, Ph. vitellinae and Ph.
      vulgatissima 2n = 34 (Xy(p)), and the karyotype of Chrysolina marginata,
      consisting of 40 chromosomes, is also described. These results are discussed with
      those previously obtained in related genera and congeneric species, giving
      further support and extending the high chromosomal variability so far found in
      this subfamily of leaf beetles.

PMID- 24279169
TI  - The effect of environmental factors on sister chromatid exchange incidence in
      domestic horse (Equus caballus) chromosomes.
AB  - The SCE test is often used as a sensitive and reliable technique in the
      biomonitoring of genotoxicity of mutagenic and carcinogenic agents. This study
      analysed the frequency of sister chromatid exchange in domestic horse chromosomes
      depending on the habitat and age of the analysed horses. The chromosome
      preparations were obtained from an in vitro culture of peripheral blood
      lymphocytes stained using the FPG technique. Both the habitat and the age
      significantly influence SCE frequency. A higher SCE incidence was observed in
      horses that lived in a large urban agglomeration than in those from the country.
      Also, a higher SCE incidence was identified in the group of horses above 6 years
      of age in comparison with the younger ones. Additionally, the frequency of SCEs
      in the first, second and third chromosomes and the X sex chromosome were analysed
      in detail. More exposed to the effect of environmental pollutants, the horses
      from the urban environment developed more double and triple SCEs in comparison
      with the village horses. The urban horses also developed quadruple SCEs, in
      addition to the less frequent exchanges.

PMID- 24279170
TI  - GammadeltaT cells positively regulate contact sensitivity (CS) reaction via
      modulation of INF-gamma, IL-12 and TNF-alpha production.
AB  - The gammadeltaT cells were identified as positive as well as negative regulators
      of immune responses. They take part in pathogen clearance, modulation of innate
      and adaptive immunity as well as in healing and tissue maintenance. The course of
      many pathological conditions such as collagen induced arthritis (CIA),
      experimental autoimmune encephalomyelitis (EAE) and airway hyperresponsiveness is
      positively regulated by gammadeltaT cells. It was shown previously that contact
      sensitivity (CS), an example of antigen-specific cell-mediated immune response,
      is also positively regulated by gammadeltaT cells. The current work confirmed the
      regulatory function of gammadeltaT cells in CS response as their depletion with
      anti-TCRdelta monoclonal antibody and complement significantly decreased adoptive
      transfer of the CS reaction. In vitro study showed that removal of gammadeltaT
      cells with magnetic beads significantly decreased the production of the
      proinflammatory cytokines IFN-gamma, IL-12 and TNF-alpha. Reconstitution of
      gammadeltaT-depleted cells with gammadeltaT-enriched cells restored cytokine
      production, proving the reversibility of the investigated process. In summary,
      gammadeltaT cells positively regulate the CS reaction via modulation of
      proinflammatory cytokine production.

PMID- 24279171
TI  - Age- and sex-related differences of morphometric, densitometric and geometric
      parameters of tibiotarsal bone in Ross broiler chickens.
AB  - For the first time computed tomography has been used to analyze densitometric and
      geometric parameters in proximal metaphyses and the mid-diaphyses of tibiotarsal
      bones in broiler chickens in posthatching development as influenced by age and
      sex. The research was conducted on 60 tibial bones of 2-, 4- and 6-week-old
      broiler chickens (Ross 308) (10 males and 10 females in each age group).
      Statistical analysis has been conducted with the use of one-way ANOVA and
      Fisher's exact test. Calculations have been performed separately for each sex,
      with age as a differentiation variable and separately for each of the
      developmental stages, with sex as a differentiation factor. Pearson's correlation
      coefficient have been calculated. Also, relative bone density has been
      determined. It was observed that volumetric bone mineral density (vBMD) in the
      diaphyses was two times higher (app. 550 cm3) than in the proximal metaphyses
      (app. 230 cm ) of the tibiae in broiler chickens. In the proximal metaphyses of
      the tibiotarsal bones, densitometric and geometrical parameters increased with
      age of the birds. Densitometric parameters (vBMD, BMC) in 6-week-old males
      displayed (slightly) higher values than in females. It is worth emphasising that
      in both sexes bone mineral content (BMC) was higher in the tibial proximal
      metaphyses than in the diaphyses. At the mid-diaphysis, most of the densitometric
      and geometrical parameters, i.e. bone mineral content (BMC), Strength-Strain
      Index (SSI), periosteal circumference (PERI_C), endosteal circumference (ENDO_C),
      cortical area(CRT_A), trabecular area (TRAB_A) and bone area (TOT_A), tended to
      grow with the birds' age. vBMD (volumetric bone mineral density in situ) is the
      only parameter that did not grow with age. It was also observed that in males in
      4 wk, vBMD in the proximal metaphyses displayed the lowest values during
      posthatching development (217.47 cm3). Also between 2 and 4 wk of the
      development, vBMD in the diaphyses decreased from 637.64 cm3 to 539.12 cm3, (P <
      or = 0.05). What is important is that vBMD and BMC are parameters that play a key
      role in bone mineralization. However, there was no correlation observed between
      them. Analysis of Pearson's correlation coefficient showed that BMC in both bone
      sections displayed positive correlation with all the geometric and densitometric
      parameters (except for vBMD). It may be concluded that vBMD is independent
      ofother parameters. The strongest correlations were observed between BMC and
      TRAB_A, and TOT_A in the proximal metaphysis, they were (r = 0.98) and (r = 0.98)
      respectively, P < or = 0.01, and between BMC and CRT_A at the mid-diaphysis (r =
      0.99), P < or = 0.05. It was demonstrated that in the group of males, decreasing
      vBMD in the proximal metaphyses between 2 and 4 wk and in the diaphyses from 2 to
      6 wk during posthatching development, as well as decreasing relative bone weight,
      from 1.03% to 0.79%, led to deformities and breaks of the tibiae, which may have
      a negative effect on the productivity of the broiler chickens flock.

PMID- 24279172
TI  - Effect of age on structural properties of intramuscular connective tissue, muscle
      fibre, collagen content and meat tenderness in pig longissimus lumborum muscle.
AB  - Changes in the structure and properties of the intramuscular connective tissue,
      muscle fibre size, collagen content and meat tenderness of m. longissimus
      lumborum during growth was studied in 45 Polish Large White (PLW) pigs
      slaughtered at 90, 150 and 210 days of age. The results show that the endomysial
      sheath in m. longissimus lumborum consists of collagen fibrils of wavy appearance
      which run in all directions and form a loose network. The arrangement of collagen
      fibrils in the endomysium and perimysium becomes denser and more regular with
      increasing age of pigs. In addition, the increase in endomysium and perimysium
      thickness was paralleled by a significant increase in muscle fibre diameter, as
      well as an increase in shear force value with chronological aging. In contrast,
      the percentage of collagen area in muscle structure and the amount of total
      collagen and amount of soluble collagen decreased gradually with age of pigs. In
      conclusion, the structural changes in the arrangement of collagen fibres in the
      architecture of intramusclular connective tissue, as well as the decrease in
      soluble collagen content in m. longissimus lumborum during growth of pigs are
      important factors influencing shear force value, and thus raw meat tenderness.

PMID- 24279173
TI  - The effects of Fasciola hepatica infection on the total antioxidant status (TAS)
      and the activity of proteases and their inhibitors in rat serum.
AB  - Fasciola hepatica infection results in increased production of reactive oxygen
      species (ROS) and changes the activity/level of antioxidants in the host
      organism, which leads to oxidative stress formation and oxidative modifications
      of lipids and proteins. Taking this into account, the aim of this study was to
      assess the antioxidant potential and the activity of proteases and their
      inhibitors in the serum of rats infected with F. hepatica. Wistar rats were
      infected per os with 30 metacercariae of F. hepatica. The total antioxidant
      status (TAS) and the activity of cathepsin G and elastase and their inhibitors
      (alpha1-antitrypsin and alpha2-macroglobulin) were determined at 4, 7, and 10
      weeks post infection (wpi). It was confirmed that F. hepatica infection leads to
      a decrease in the antioxidant capacity of serum, which was manifested as a
      reduction in total antioxidant status by about 24, 39, and 27%, respectively, at
      4, 7, and 10 wpi. At the same time, the activity of proteases increased
      significantly: cathepsin G by about 25, 37, and 30%, and elastase by about 18,
      16, and 9% during the course of F. hepatica infection, compared with the control
      group. However, the activity of alpha1-antitrypsin was significantly reduced, by
      36, 55, and 25%, while alpha2-macroglobulin activity was reduced by about 14, 17,
      and 8% during the same period of fasciolosis. These results indicate that the
      shift in protease/antiprotease balance towards protease action observed during
      the course of fasciolosis may result in a decrease in host antioxidant capacity.

PMID- 24279174
TI  - Emergence of Palmistichus elaeisis Delvare & Lasalle, 1993 (Hymenoptera:
      Eulophidae) from pupae of Heraclides anchisiades capys (Hubner, [1809])
      (Lepidoptera: Papilionidae) in the laboratory.
AB  - Heraclides anchisiades capys (Hubner, [1809]) (Lepidoptera: Papilionidae) is an
      abundant insect pest on crops of Citrus spp. (Rutaceae) in Brazil and pupae of
      this defoliator could be used for the mass rearing of parasitoids. The aim of
      this study was to evaluate the parasitism of Palmistichus elaeisis Delvare &
      LaSalle, 1993 (Hymenoptera: Eulophidae) on H. anchisiades capys pupae in the
      laboratory. Twenty 1-day-old H. anchisiades capys pupae were individualized in
      test tubes (14 cm length x 2.2 cm diameter) with a drop of honey as food and with
      ten mated P. elaeisis females for ten days. The duration of the life cycle (egg
      to adult), emergence rate, total individuals emerged per pupa, sex ratio, size of
      the body and longevity of P. elaeisis males and females emerged from H.
      anchisiades capys pupae were evaluated. The duration of the life cycle of P.
      elaeisis was 21.15 +/- 0.15 days. Forty percent of H. anchisiades capys pupae
      showed emergence of parasitoids, with an average of 323 +/- 38 individuals from
      each one and a sex ratio of 0.95 +/- 0.02. The total number of parasitoids
      emerged was 2,584 individuals. The size of the body and the head capsule (mm) of
      female and male P. elaeisis progeny were 1.92 +/- 0.04; 0.52 +/- 0.02 and 1.28 +/
      0.04; 0.40 +/- 0.02, respectively. The average longevity was 23.72 +/- 1.15 days
      for females and 30.1 +/- 2.42 days for males of P. elaeisis. Heraclides
      anchisiades capys, abundant on crops of Citrus spp. in Brazil, has potential to
      be used as a host for mass rearing of P. elaeisis in the laboratory for
      biological control programs.

PMID- 24279175
TI  - Correlations between social context and fecal glucocorticoid metabolite
      concentrations in free-ranging female gray-cheeked mangabeys (Lophocebus
      albigena) in Kibale National Park, Uganda.
AB  - An elevated concentration of glucocorticoids is an indicator of stress, and
      chronically high glucocorticoid levels are often associated with poor health and
      reduced fertility. We explored conditions that might be stressors in the lives of
      adult female gray-cheeked mangabeys (Lophocebus albigena) by measuring fecal
      glucocorticoid metabolites (fGCM) concentrations. During a six-month study we
      collected 109 fecal samples from 28 adult females from five groups in Kibale
      National Park, Uganda. We examined fecal fGCM levels of individual females
      relative to their own reproductive status (cycling or not cycling) and that of
      other females and to the presence of newcomer (immigrant) males. We found
      elevated fGCM concentrations in females when other females in their groups were
      at the peak of sexual swelling, and when immigrant males joined the group.

PMID- 24279176
TI  - The effect of the cAMP analogue, dbcAMP, on proliferation and apoptosis of rabbit
      oviductal cells.
AB  - It was previously documented that cyclic AMP (cAMP)-dependent intracellular
      mechanisms can be involved in control of reproductive processes, and
      pharmacological regulators of these mechanisms could be practically used to
      improve rabbit fertility (Sirotkin et al. 2008; Sirotkin et al. 2010a; Chrenek et
      al. 2012). Changes in fertility could be due to changes in oviductal functions.
      The aim of our study was to examine the involvement of cAMP-dependent
      intracellular mechanisms in control of oviductal cell functions, in particular
      the influence of dbcAMP, a cAMP agonistic analogue, on proliferation and
      apoptosis of cultured oviductal cells. For this purpose, we compared the
      expression of markers of proliferation (PCNA, cyclin B1) and apoptosis (bax and
      bcl-2) in the oviduct epithelial cells isolated from rabbits, whose ovarian and
      oviductal cycle was induced by gonadotropins alone or in combination with dbcAMP
      (50 microg/animal) by using immunocytochemistry. It was observed that dbcAMP
      administration caused an increase in the proportion of cells containing PCNA, but
      not cyclin B1, bax or bcl-2. Higher expression of PCNA, but not cyclin B1, in the
      dbcAMP-treated group suggests that the dbcAMP administration can stimulate
      oviductal cell proliferation, probably promoting transition of cells from G0 to
      G1 and S-phase of the cell cycle. No influence of dbcAMP administration on
      regulators and markers of apoptosis (pro-apoptotic - bax and anti-apoptotic - bcl
      2) suggests that dbcAMP is probably not involved in the control of apoptosis in
      rabbit oviduct epithelial cells. The involvement of cAMP-dependent intracellular
      mechanisms in control of oviduct functions is assumed in this study. This is the
      first demonstration that dbcAMP can stimulate proliferation of the oviduct
      epithelial cells without influencing their apoptosis.

PMID- 24279177
TI  - Novel aspects of cytokine action in porcine uterus--endometrial and myometrial
      production of estrone (E1) in the presence of interleukin 1beta (IL1beta),
      interleukin 6 (IL6) and tumor necrosis factor (TNFalpha)--in vitro study.
AB  - Interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor
      alpha (TNFalpha) increased (P < 0.05) estrone (E1) release from endometrial
      explants of pregnant pigs on days 10 to 11 after 12 h of tissue incubation in
      vitro with cytokines and on days 12 to 13 after 6 h of incubation. After 12 h of
      incubation on days 12 to 13 and 15 to 16 of pregnancy only IL6 increased E1
      release. In non-gravid pigs IL1beta, IL6 and TNFalpha increased endometrial E1
      release only on days 12 to 13 of the estrous cycle. The cytokines did not affect
      myometrial E1 release on days 10 to 11 and 15 to 16 ofpregnancy. On days 12 to 13
      of pregnancy myometrial release of E1 was markedly increased in response to IL
      1beta and IL6. In cyclic pigs only IL6 after 6 h of in vitro incubation increased
      myometrial E1 release on days 12 to 13 and 15 to 16. Progesterone (P4) increased
      both endometrial and myometrial release of E1 during the studied days of
      pregnancy and the estrous cycle, except for endometrial release on days 10 to 11
      and 15 to 16 of the estrous cycle after 6 h of in vitro incubation. The results
      demonstrated that these cytokines may regulate the release of E1 both from the
      endometrium and myometrium harvested from gravid and non-gravid pigs. The results
      showed a pivotal role of IL 1beta, IL6 and TNFalpha in the regulation of E1
      release in the porcine uterus in vitro.

PMID- 24279178
TI  - Nonspecific effects of ligands on the beta-adrenergic receptors in rabbit
      abdominal aorta in vitro.
AB  - The study was conducted on 30 New Zealand rabbits weighing 3-4 kg from which
      sample strips of the abdominal aorta were collected. The study investigated the
      in vitro reaction of rabbit aorta smooth muscle to ligands binding to beta
      adrenergic receptors. The response of aortic strips to beta-adrenergic receptor
      agonists (dobutamine, isoproterenol, salbutamol) and the influence of beta
      adrenergic receptor antagonists (propranolol, betaxolol) on contractile activity
      was determined. All tested agonists induced contraction of the rabbit abdominal
      aorta muscle in a concentration-dependent manner (dobutamine >> isoproterenol >
      salbutamol). Enhanced reaction to low concentrations of agonists (dobutamine,
      isoproterenol) after administration of propranolol and inhibition of
      contractility in the presence of high concentrations thereof (dobutamine,
      salbutamol) was observed. Maximal reaction to agonists decreased after betaxolol
      pretreatment. The results indicate that all the substances with beta-agonist
      activity also possess contracting properties (presumably by acting at alpha
      adrenergic receptors), but are much weaker in the case of isoproterenol and
      salbutamol than for dobutamine. Propranolol and betaxolol reduce the contractile
      response of smooth muscle using probably other mechanisms than those associated
      with adrenergic receptors.

PMID- 24279179
TI  - Expression and localization of growth hormone receptor in the oviduct of the
      laying hen (Gallus domesticus).
AB  - The purpose of the present study was to examine growth hormone receptor (GHR)
      gene expression by real-time PCR and demonstrate immunocytochemically the
      localization of GHR in four chicken oviductal parts, i.e. infundibulum, magnum,
      isthmus and shell gland. Experiments were carried out on Hy-Line laying hens
      decapitated 2 h after oviposition. GHR mRNA was expressed in all examined
      oviductal segments with a significantly lower level in the infundibulum in
      comparison to other parts of the oviduct. Specific GHR immunoreactivity was also
      detected in the wall of the oviduct. The intensity of the staining was as
      follows: infundibulum < or = isthmus < or = shell gland < or = magnum. In all
      oviductal parts, a positive reaction for GHR was observed in the mucosa whereas a
      very weak or no reaction was observed in the stroma. Within the mucosa a strong
      reaction for GHR was observed in the epithelium of the infundibulum and in the
      tubular gland of the magnum, isthmus and shell gland. Immunoreactivity for GHR
      was very weak in the mucosal epithelium of the magnum, isthmus and shell gland.
      In conclusion, the results point to the possibility of an important role of GH in
      oviduct functions in domestic hens.

PMID- 24279180
TI  - In vitro effects of TCDD, PCB126 and PCB153 on estrogen receptors, caspases and
      metalloproteinase-2 mRNA expression in the chicken shell gland.
AB  - Among the environmental chemicals which disturb endocrine functions, dioxins and
      polychlorinated biphenyls (PCBs) are known as the most toxic. Numerous studies in
      mammals revealed that dioxins and PCBs disrupt functions of the uterus, delay
      implantation and increase embryo loss. The direct effect of these chemicals on
      the avian oviduct is not known. Therefore, in the study chicken shell gland
      tissues were used to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), coplanar PCB126 and non-coplanar PCB153 on estrogen receptors (ERs),
      initiator caspase-1, executioner caspase-3 and metalloproteinase-2 (MMP-2) mRNA
      expression. Fragments of shell gland tissue isolated from the laying chicken were
      incubated for 24h with TCDD (100nM), PCB126 (100nM) or PCB153 (100 microM).
      Quantitative PCR analysis showed that: (1) TCDD increased ER beta (ERbeta) mRNA
      expression, (2) PCB126 increased ER alpha (ERalpha), ERbeta and caspase-1, and
      decreased MMP-2 mRNA expression, (3) PCB153 elevated the ERbeta and caspase-1
      expression levels and (4) expression of caspase-3 was not altered by any
      investigated xenobiotics. The results obtained using the shell gland explants
      model indicate that dioxins and PCBs have a direct effect on the chicken oviduct,
      especially the shell gland, by affecting the expression of genes involved in the
      function of this oviductal segment. It is suggested that coplanar PCBs such as
      PCB126, by changing cellular and extracellular regulators gene expression, may
      lead to disruption of shell gland activity and impair egg components formed in
      this organ.

PMID- 24279181
TI  - The central nervous system of heterosymelic individuals of the spider Tegenaria
      atrica.
AB  - This paper presents the results of research on the nervous system in individuals
      of Tegenaria atrica with heterosymely of walking legs, a pedipalp and the first
      walking leg. Temperatures alternating between 14 degrees and 32 degrees C every
      12 hours were applied as a teratogenic factor in the early stage of
      embryogenesis. From the thus obtained specimens, histological sections were taken
      using the paraffin method and then stained. Analysis of the nervous system in
      individuals with partial heterosymely of walking legs showed no significant
      changes in the structure of subesophageal nervous mass. In most of the studied
      individuals with partial and total heterosymely of a pedipalp and walking leg no
      changes were observed in the relevant parts of the nervous system either,
      although in two cases a fusion of nerve ganglia was noted, from which the nerves
      branched off towards the conjoined legs.

PMID- 24279182
TI  - Getting comfortable with death & near-death experiences. Medical metaphysics:
      what is a "good death"? What happens when we almost die?

PMID- 24279183
TI  - Getting comfortable with death & near-death experiences. Near-death experiences:
      an essay in medicine & philosophy.
AB  - Near-death experiences are an ancient and very common phenomenon that spans from
      ancient philosophy, religion and healing to the most modern clinical practice of
      medicine. Probably we are not much closer to an ultimate explanation of NDEs than
      were early thinkers like Plato and Democritus. Puzzling cases of near-death
      experiences continue to come to light and the ancient debate about what they mean
      continues unabated.

PMID- 24279184
TI  - Getting comfortable with death & near death experiences. How doctors die: a model
      for everyone?

PMID- 24279185
TI  - Non-assigned Medicare payment increases practice revenue & lowers Medicare costs.
AB  - Private practice physicians can increase practice revenue and also save Medicare
      money. What seems like a paradox is instead a choice. The non-assigned Medicare
      payment option allows physicians to bill 8% more for their services. This also
      decreases Medicare payment 5%. Selecting the non-assigned payment method does not
      require permission from Medicare or any Medicare contractor. This is a physician
      decision and for 2014 must be made between mid-November and year end 2013.

PMID- 24279186
TI  - Accountable care organizations: are we even at the table?

PMID- 24279187
TI  - Are we too fat? Or are we not fat enough?

PMID- 24279188
TI  - Transforming the future of medicine.

PMID- 24279189
TI  - Neurodegenerative disorders of aging: the down side of rising longevity.

PMID- 24279190
TI  - Alzheimer disease: current concepts & future directions.
AB  - Alzheimer disease (AD) is the most common cause of dementia in individuals over
      age 65, and is expected to cause a major public health crisis as the number of
      older Americans rapidly expands in the next three decades. Herein, we review
      current strategies for diagnosis and management of AD, and discuss ongoing
      clinical research and future therapeutic directions in the battle against this
      devastating disease.

PMID- 24279191
TI  - Advances in diagnostic testing for Alzheimer disease.
AB  - The diagnosis of Alzheimer disease (AD) dementia is based primarily on the
      clinical history and examination, but advances in understanding the
      pathophysiology of AD have led to new diagnostic methods. When used
      appropriately, the tests can provide strong positive or negative evidence AD
      dementia. This article described which patients may benefit from additional
      testing using Cerebrospinal Fluid (CSF) biomarkers, amyloid imaging, quantitative
      structural magnetic resonance imaging (MRI), and fluoro-deoxyglucose positron
      emission tomography (FDG-PET).

PMID- 24279192
TI  - Parkinson disease in the elderly adult.
AB  - Parkinson disease is the second most neurodegenerative disease, after Alzheimer
      disease, that affects up to two million Americans, the overwhelming majority of
      whom are aged 60 and older. The changing demographics of the country place more
      Americans at risk for Parkinson disease (PD) than ever before. Primary care
      physicians treat the majority of PD patients in the United States. Here I review
      diagnosis and treatment strategies for idiopathic Parkinson disease in the
      elderly adult.

PMID- 24279193
TI  - Unravelling the mysteries of frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a clinical term that encompasses the
      neurodegenerative diseases that selectively affect the frontal and anterior
      temporal lobes of the brain. FTD, which is underdiagnosed in clinical settings,
      presents with behavioral changes or deficits in language. The last two decades
      have seen tremendous advances in the appreciation of the clinical assessment,
      genetics, and molecular pathology of this group of enigmatic diseases, thus
      offering hope for the development of rational therapeutic strategies.

PMID- 24279194
TI  - Management of amyotrophic lateral sclerosis.
AB  - Motor Neuron Diseases (MNDs) are neurological disorders characterized by the
      selective and progressive degeneration of motor neurons. Amyotrophic Lateral
      Sclerosis (ALS), commonly known as Lou Gehrig's disease, is the most common. ALS
      causes diffuse muscle weakness and death secondary to respiratory failure. The
      diagnosis is made clinically, supported by electrodiagnostic testing. Although
      medications are limited, careful attention to breathing, nutrition, and patient
      mobility can have a major, positive impact on the course of the disease.

PMID- 24279195
TI  - Diagnosis and evaluation of a patient with rapidly progressive dementia.
AB  - While the most common dementia is Alzheimer disease (AD), a detailed history is
      needed to rule out rapidly progressive dementias (RPDs). RPDs are less than two
      years in duration and have a rate of progression faster typical neurodegenerative
      diseases. Identification of RPDs is important as some are treatable. This review
      focuses on the spectrum of RPDs, with special emphasis on paraneoplastic
      disorders and Creutzfeldt-Jakob disease (CJD).

PMID- 24279197
TI  - Belgian guidelines for safe regional anesthesia and obstetric anesthesia and
      analgesia.

PMID- 24279196
TI  - A case for neuroprotection in ophthalmology: developments in translational
      research.
AB  - Cellular aging occurs by the lifelong accumulation of oxidative damage leading to
      neuronal apoptosis, termed 'neurodegeneration', and the functional deficits of
      aging. Loss of visual function is one of the most important quality of life
      measures for older adults. We discuss recent clinical and laboratory advances in
      the neuroprotective treatment of the aging eye with particular emphasis on the
      three major ocular neurodegenerative conditions: glaucoma, age-related macular
      degeneration (AMD), and diabetic retinopathy (DR).

PMID- 24279198
TI  - Recommendations and guidelines for obstetric anesthesia in Belgium.

PMID- 24279199
TI  - Clinical guidelines for the practice of peripheral nerve blocks in the adult.
AB  - These guidelines, made by BARA, are, like the "Safety First Guidelines" of the
      SARB, clinical recomendations for a good and safe practice when performing
      peripheral nerve blocks (PNB). These recommendations were made according to the
      most recent literature and experts opinion and are therefore prone to changes due
      to evolution of literature. The guidelines deal with "Informed Consent",
      preoperative visit, monitoring, equipment and the PNB procedure itself regardless
      of using ultrasound or neurostimultion or both. Advise is given when combining a
      PNB with general anesthesia and when a catheter technique is used.

PMID- 24279200
TI  - Transient perioperative visual loss after an elective neurosurgical procedure.
AB  - OBJECTIVE: To describe a case of reversible visual loss after a neurosurgical
      intervention and to discuss the role of the prone position as a potential risk
      factor. OBSERVATION: A 63-year-old woman without significant medical previous
      history underwent elective resection of a left parieto-occipital meningioma.
      Preoperatively, the patient presented a right homonymous lower quadranopsia. The
      surgical procedure was not complicated. The patient was positioned in prone with
      a mild inclination of the table in reverse Trendelenburg position. The head was
      maintained in a Mayfield skull clamp, and ocular compression was excluded. There
      was no significant hypotension, hemodilution or vasopressors infusion during the
      procedure. Immediately after recovery from anesthesia, the patient experienced
      total blindness and flash visual evoked potentials confirmed the absence of
      retinal, primary or late occipital activities. A progressive, but finally
      complete recovery started after 24 hours. CONCLUSION: This case illustrates the
      individual risk for visual injury after the prone position during some
      neurosurgical interventions.

PMID- 24279201
TI  - Starvation-induced ketoacidosis in bariatric surgery: a case report.
AB  - Patients scheduled for bariatric surgery are instructed to stick to a low
      calorie, protein sparing diet for a brief period before their operation. However,
      too low calorie intake can lead to starvation ketoacidosis. We describe a case of
      a patient who rigorously restricted oral calorie input, even more than
      prescribed. Immediately after surgery, a marked metabolic acidosis was noted.
      This ketoacidosis was successfully treated with oral glucose substitution. A
      superposed respiratory acidosis could have had detrimental effects.

PMID- 24279202
TI  - Horner's syndrome in the prone position--a case report.
AB  - We report the case of a patient who developed a post-operative Homer's syndrome
      after non-cervical surgery. Part of the surgery was in the prone position. A
      hypothesis incriminating the prone position as being a possible cause of this
      syndrome is suggested.

PMID- 24279203
TI  - Health insurance exchanges: coming to a state near you.

PMID- 24279204
TI  - If you want patients to be stewards of their kidney health, give them tools that
      work.

PMID- 24279205
TI  - Creating an open dialogue on improving dialysis care.

PMID- 24279206
TI  - New tool helps predict AKI, death.

PMID- 24279207
TI  - Nephrology nursing - a view from the other end of the dialysis needle.

PMID- 24279208
TI  - Five challenges impacting nephrology nursing.
AB  - Nephrology nurses are continually facing unique challenges in their work
      environments. The development of skills to help navigate these challenges while
      continuing to provide quality care in our specialty critical.

PMID- 24279209
TI  - Challenges for dialysis facility medical directors and impact on patient care.
AB  - My service within the RPA began with my need to be a part of the solution, to
      help navigate the direction of inevitable change, and to ensure we do not lose
      focus of our ultimate goal as nephrologists-the provision of excellent kidney
      care. I would encourage all of you to participate in this process as well. It is
      essential that we maintain our independence, ethics and principals, and
      excellence in our roles and responsibilities as nephrologists and dialysis unit
      medical directors, especially in challenging times such as these. Engaging with
      the RPA in advocating redress of the ESRD PPS proposed 9.4% cut and support for
      maintaining our critical role as independent dialysis unit medical directors is
      one way we can make a difference. Become involved in the process. Communicate
      your concerns to legislators and policy makers. Only with the support of our
      community and a firm commitment to our goals can we effect change and ensure
      nephrology patients continue to be well served in the years to come.

PMID- 24279210
TI  - How new interpretation of LVPA will hurt hospital programs.

PMID- 24279211
TI  - How applying lean principles in dialysis improved efficiency and patient
      satisfaction.

PMID- 24279212
TI  - Putting patients' interests first.

PMID- 24279213
TI  - The coping-retained bridge: a modified approach to conventional bridge design-
      review and case report.
AB  - Missing teeth may be restored with conventional bridgework. A modified approach
      to traditional bridge design may be necessary to restore edentulous spaces in the
      presence of poorly aligned abutment teeth and abutment teeth of guarded
      prognosis. The coping bridge is a useful technique in the dentist's armamentarium
      for patients in whom implant-supported or removable prostheses are inappropriate.
      This paper examines the use of coping-retained bridges as a modification on
      traditional design and discusses how these appliances may be applied in general
      practice. A case report is presented describing the application of this design in
      general practice. CLINICAL RELEVANCE: Applying a modified approach to bridge
      design may allow complicated edentulous spaces to be restored successfully in
      general practice.

PMID- 24279214
TI  - Special care dentistry: part 1. Dental management of patients with inherited
      bleeding disorders.
AB  - The most common cause of excessive bleeding is idiopathic, but bleeding can also
      be caused by inherited or acquired conditions associated with vascular defects,
      platelet defects or coagulation disorders. This paper will cover inherited
      bleeding disorders. Every clinician will encounter a patient who complains of
      prolonged bleeding following certain procedures; most commonly dental
      extractions. In the majority of cases the cause is often a local one and can be
      managed using simple local measures. However, prolonged post-operative bleeding
      following dental treatment might be one of the first signs of a bleeding disorder
      in an undiagnosed patient, necessitating referral for further investigations.
      Some patients may present with an already confirmed diagnosis of a bleeding
      disorder, requiring appropriate treatment planning and dental management in an
      appropriate setting with haematological advice. This paper will provide guidance
      on how to achieve this. CLINICAL RELEVANCE: To update clinicians on the dental
      management of patients with inherited bleeding disorders and how to decide the
      most appropriate setting for the provision of dental care.

PMID- 24279215
TI  - Can oil lubricated dental handpieces be sterilized?: Part 2. Literature review.
AB  - A literature search revealed six laboratory-based microbial challenge studies
      which support the opinion that oil contamination does not prevent successful
      sterilization of the lumen of dental handpieces. However, a detailed appraisal of
      these papers revealed lack of detail in the cleaning methods used prior to
      sterilization and none of the papers considered the risks of prion contamination.
      CLINICAL RELEVANCE: An examination of the evidence base on sterilization of oil
      lubricated handpieces is of potential value to dental clinicians and their teams.

PMID- 24279216
TI  - Printed radiographs--is what you see what you get?
AB  - Digital dental radiography allows for exchange of images between primary and
      secondary care. However, it is common practice for radiographs to be printed out
      and attached to referrals.This study investigates the loss of diagnostic
      information of printed radiographs compared to the on-screen digital image.The
      best quality was achieved with images printed onto radiographic film or onto
      photographic paper with an inkjet printer. Laser and inkjet printer output onto
      80 gsm office paper resulted in a loss of diagnostic information. Wherever
      possible, radiographs should be transmitted digitally between clinicians to
      maintain image integrity. CLINICAL RELEVANCE: This paper illustrates the
      potential pitfalls of printing radiographs to be sent with referrals.

PMID- 24279217
TI  - Taking the trauma out of trauma: an easy to follow guide for the management of
      trauma to the permanent dentition.
AB  - Treatment of dental trauma can be an infrequent, unpredictable and stressful
      experience for a dental practitioner. Correct diagnosis and management of such
      cases is of primary importance in the prognosis of the affected dentition. We
      have therefore constructed a number of easy to follow algorithms in management,
      both short and long term, for the range of traumatic injuries that can affect the
      permanent dentition. CLINICAL RELEVANCE: Immediate as well as longer term
      management of dental trauma cases can be difficult, therefore a clear treatment
      plan is of great importance in successful results.

PMID- 24279219
TI  - Giant cell arteritis affecting the tongue: a case report and review of the
      literature.
AB  - Giant cell arteritis (GCA) is a systemic vasculitis with symptoms that could
      cause a patient to present to a general dental practitioner. A case of GCA that
      presented as headache, jaw claudication, unilateral visual loss and tongue
      ulceration leading to necrosis is reported and the literature reviewed, with an
      emphasis on dentally relevant aspects. It is vital that GCA is not overlooked in
      patients over the age of 50 with unexplained dental pain, tissue necrosis or jaw
      pain which may be misdiagnosed as a temporomandibular joint disorder. Early
      diagnosis and prompt treatment is the key to preventing visual loss. Early
      referral in such cases would be warranted. CLINICAL RELEVANCE: Dental clinicians
      may play a part in the early diagnosis of GCA by having a high index of suspicion
      for its symptoms in patients, so that devastating ischaemic consequences, such as
      irreversible visual loss, can be prevented.

PMID- 24279218
TI  - The application of clinical audit to improve pain control following third molar
      surgery.
AB  - A telephone survey was used to assess adequacy of pain control after third molar
      removal in a series of three audits. After each audit, factors contributing to
      failure to control pain adequately and poor patient compliance with our analgesic
      regimen were identified. Changes in practice were then introduced to remedy areas
      of weakness and improve outcome. Despite an apparently sound protocol for the
      prescription of analgesics for patients having third molar surgery, the first
      audit revealed that 53% of patients experienced moderate to severe pain. After
      the introduction of written patient instructions to clarify the use of post
      operative analgesics, the second audit demonstrated that 86% had their pain
      managed successfully. After subsequently increasing the post-operative Ibuprofen
      doses from 400 mg to 600 mg, the third audit showed that 96% of patients had
      satisfactory pain control. The use of clinical audit with an evidence-based
      analgesic regimen and clear, written patient instruction has improved post
      operative pain control. CLINICAL RELEVANCE: This paper demonstrates the
      usefulness of clinical audit for the monitoring and improvement of pain control
      and analgesic prescribing regimens following oral surgery, which in turn may
      improve patient experience and outcome.

PMID- 24279220
TI  - Appraisal for general dental practitioners.
AB  - Appraisal has been a key component of staff management of most organizations for
      more than a decade. This article explores the principles, benefits and stages for
      effective appraisal in primary dental care. CLINICAL RELEVANCE: Reviewing what
      works and what does not and reflection on these points are key to developing
      professional skills. Appraisal is a formalized way of reflecting on the past to
      help a professional plan for his/her future and thereby, ideally, improve patient
      care.

PMID- 24279221
TI  - Oral medicine: 11. Lumps and swellings: mouth.

PMID- 24279222
TI  - Technique tips--greenstick modification of dentures Prior to the replica
      technique: 'how we do it'.

PMID- 24279223
TI  - Physical signs for the general dental practitioner. Case 105. Arterial emboli.

PMID- 24279224
TI  - Trichromatic and dichromatic relative sensitivity to green light in a mild
      hypoxic environment.
AB  - INTRODUCTION: Several studies have reported that individuals with normal color
      vision have a relative decrease in sensitivity to green light in hypoxic
      environments approximating altitudes above 4000 m. Because there is little
      available information describing the effects of mild hypoxic environments (less
      than 4000 m) in subjects with deficient color-vision, we examined the effect of
      mild hypoxia on the relative sensitivity to green light for color-normal and
      color-deficient subjects. METHODS: Relative sensitivity to the green light was
      measured using the Medmont C-100 at ground and 3780 m in an altitude chamber.
      There were 30 subjects, 13 with normal color vision and 17 with a congenital red
      green defect, who participated in the study. The relative sensitivity to the
      green light was determined from the average of four settings measured during the
      4.5-h trial. RESULTS: Color-normals and anomalous trichromats showed a small
      decrease in the relative sensitivity to the green light at 3780 m compared to
      ground. In contrast to the trichromatic results, the relative sensitivity of the
      dichromats to the green light did not differ between 3780 m and ground.
      DISCUSSION: Our results show that a decrease in the relative sensitivity to green
      light can occur in hypoxic environments that are equivalent to altitudes greater
      than 3700 m in individuals with trichromatic but not dichromatic color vision.
      Although the change in sensitivity was significant, it was small and unlikely to
      have any operational impact.

PMID- 24279225
TI  - Variability in perceived tilt during a roll plane canal-otolith conflict in a
      gondola centrifuge.
AB  - BACKGROUND: During a simulated coordinated turn in a gondola centrifuge, the
      perceived roll-tilt, quantified as the subjective visual horizontal (SVH), may
      differ tenfold between individuals. One aim of this study was to discern whether
      this variability reflects real individual characteristics or is due to noise or
      day-to-day variation. We also wanted to establish whether there are any
      habituation or learning effects of the centrifuge test. METHODS: In nine
      nonpilots (NP) and nine student pilots (SP), with a flight experience of 150 h,
      the SVH was measured using an adjustable luminous line in darkness. At two test
      occasions (T1, T2) (interval 5-14 d) subjects underwent two runs (R1, R2;
      acceleration to 2 G in 10 s, gondola inclination 60 degrees, 5 min at 2 G,
      deceleration to 1 g in 10 s, interval between runs 5 min) in a centrifuge (r =
      9.1 m). Initial and final SVH was determined for each individual run. RESULTS:
      Acceleration of the centrifuge induced a tilt of the SVH. At T1 R1, this SVH tilt
      was, in NP, initially 24 +/- 18 degrees and finally 8 +/- 10 degrees. The
      corresponding values for SP were 28 +/- 18 degrees and 31 +/- 33 degrees. The SVH
      tilt was slightly larger at R2 than at R1. There was no difference between T1 and
      T2. Reliability coefficients ranged between 0.86 and 0.98 for NP and between 0.78
      and 0.99 for SP. CONCLUSION: The large interindividual variability combined with
      a very high reproducibility suggests the existence of persistent individual
      characteristics in the perception of complex vestibular stimuli. Habituation or
      learning effects of gondola centrifugation appears to be small.

PMID- 24279226
TI  - Cardiovascular regulation during body unweighting by lower body positive
      pressure.
AB  - BACKGROUND: We hypothesized that human cardiovascular responses to standing in
      reduced gravity environments, as on the Moon or Mars, could be modeled using a
      lower body positive pressure (LBPP) chamber. METHODS: Heart rate, blood pressure,
      body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance,
      and baroreflex control of the heart and periphery plus echocardiographic measures
      of cardiac function were recorded from seven men and seven women supine and
      standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). RESULTS:
      The fluid shifted from the chest was greater when standing at 100% BW than at 20%
      and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to
      moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in
      smaller decreases in stroke volume and pulse pressure, smaller increases in heart
      rate and smaller decreases in parasympathetic control of heart rate, baroreflex
      slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic
      drive to the heart and periphery. However, peripheral vascular resistance,
      systolic pressure, and baroreflex effectiveness were elevated during 20% and 40%
      BW, compared to supine and standing at 100% BW. DISCUSSION: Standing at reduced
      bodyweight suppressed indexes of sympathetic control of heart rate and peripheral
      vasomotion. Regulatory responses indicated a combination of arterial and
      cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex
      sensitivity appeared to be more under cardiopulmonary control while baroreflex
      effectiveness appeared to be driven more by the arterial baroreflex.

PMID- 24279227
TI  - Performance during simple and complex military psychomotor tasks at various
      altitudes.
AB  - BACKGROUND: The purposes were to determine the following: 1) the threshold
      between 2500-4300 m at which simple and complex military task performance is
      degraded; 2) whether the degree of degradation, if any, is related to changes in
      altitude illness, fatigue, or sleepiness at a given altitude; and 3) whether the
      level of hypoxemia, independent of altitude, affects simple and complex military
      task performance. METHODS: There were 57 lowlanders (mean +/- SD; 22 +/- 3 yr; 79
      +/- 12 kg) who were exposed to either 2500 m (N = 17), 3000 m (N = 12), 3500 m (N
      = 11), or 4300 m (N = 17). Disassembly and reassembly of a weapon (DsAs, simple),
      rifle marksmanship (RM, complex), acute mountain sickness (AMS), fatigue,
      sleepiness, and arterial oxygen saturation (SaO2) were measured at sea level
      (SL), and after 8 h (HA8) and 30 h (HA30) of exposure to each altitude. RESULTS:
      DsAs did not change from SL to HA8 or HA30 at any altitude. RM speed (target/min)
      decreased from SL (20 +/- 1.5) to HA8 (17 +/- 1.5) and HA30 (17 +/- 3) only at
      4300 m. AMS, fatigue, and sleepiness were increased and SaO2 was decreased at
      2500 m and above. Increased sleepiness was the only variable associated with
      decreased RM speed at 4300 m (r = -0.67; P = 0.004). Greater hypoxemia,
      independent of altitude, was associated with greater decrements in RM speed (r =
      0.27; P = 0.04). CONCLUSIONS: Simple psychomotor performance was not affected by
      exposures between 2500-4300 m; however, complex psychomotor performance (i.e., RM
      speed) was degraded at 4300 m most likely due to increased sleepiness. Greater
      levels of hypoxemia were associated with greater decrements in RM speed.

PMID- 24279228
TI  - Body fatness, body core temperature, and heat loss during moderate-intensity
      exercise.
AB  - PURPOSE: This study examined the influence of body fatness on body core
      temperature and heat loss responses during moderate-intensity exercise. METHODS:
      Nine men with lower body fat and eight men with higher body fat, matched for
      aerobic fitness, completed 1 h of recumbent cycling at the same absolute
      intensity in a warm environment (30 degrees C, 40% RH). Percent body fat was
      measured by hydrostatic weighing, using oxygen dilution to determine residual
      volume. Esophageal temperature (T(es)), mean skin temperature (T(sk)), and local
      sweat rate (m(sw)) were measured at rest and continuously during exercise while
      forearm blood flow (FBF) was measured at rest and every 10 min during exercise.
      RESULTS: The lower body fat and higher body fat groups were successfully matched
      for aerobic fitness, removing the influence of body fatness, given that
      V/O2(peak) was 50.72 +/- 7.34 and 50.43 +/- 5.01 ml x kg LBM(-1) x min(-1),
      respectively. When compared to lower body fat individuals, % body fat, body
      surface area (A(D)), and body mass were higher and A(D)/ mass was lower in higher
      body fat individuals. T(es), T(sk), FBF, m(sw), and the slope of m(sw):T(es) were
      not different between groups. Metabolic heat production was similar between the
      lower body fat (299.7 +/- 40.5 W x m(-2)) and higher body fat (288.1 +/- 30.6 W x
      m(-2)) subjects, respectively. Dry and evaporative heat loss, as well as heat
      storage during exercise, were not different between groups. CONCLUSION: These
      data suggest that there is no effect of body fatness on body core temperature or
      heat loss responses during moderate-intensity exercise in a warm environment.

PMID- 24279229
TI  - Cognition at altitude: impairment in executive and memory processes under hypoxic
      conditions.
AB  - BACKGROUND: The negative effect of hypoxia on cognitive function has been well
      described. However, less has been published regarding cognitive dysfunction
      resulting from hypoxia produced by exposure to different altitudes. METHODS: We
      measured short-term and working memory capacity (Digit Span tasks), cognitive
      flexibility and selective attention (Word-Color Stroop Task), and executive
      functioning (Trailmaking A and B tests) at baseline and simulated altitudes equal
      to 17,500 ft (5334 m) and 25,000 ft (7620 m) in order to obtain more information
      about the role of altitude exposure on cognitive tasks important for optimal
      functioning in the aviation environment. RESULTS: Behavioral observations
      indicated that hypoxia was induced at different simulated altitudes. Marked
      declines in cognitive performance were also observed for all tests at 25,000 ft,
      with scores indicating greater impairment in this condition relative to others.
      Subjects also showed greater impairment when scores obtained in the 17,500-ft
      condition were compared to baseline, although the effects were not as clearly
      defined relative to the 25,000 vs. baseline contrasts. DISCUSSION: The results of
      this study suggest that electronic versions of these tests may be useful in
      screening for acute symptoms of hypoxia and could provide insight into how
      discrete cognitive processes become impaired with oxygen deprivation at various
      altitudes. Given that these tests also assess neuropsychological functioning, our
      results allow for inferences to be made about the effects of hypoxia on human
      brain functioning.

PMID- 24279230
TI  - Oral contraceptive use and acute mountain sickness in South Pole workers.
AB  - INTRODUCTION: Progesterone has a number of properties that could influence the
      development of acute mountain sickness (AMS), including anti-inflammation,
      respiratory smooth muscle relaxation, ventilatory stimulation, and antidiuretic
      characteristics. Oral contraceptive (OC) use decreases levels of circulating
      progesterone by preventing ovulation. We hypothesized rates of AMS development
      would be significantly higher in OC users as compared to Non-OC users in a
      population traveling rapidly to the South Pole. METHODS: There were 50 female
      subjects (OC N = 13, no OC N = 37) who traveled by airplane from Sea Level (SL)
      to Altitude (ALTD) (-3200 m) in < 4 h and were monitored for the development of
      AMS. SL and ALTD measurements of anthropometrics, vital signs, hematologic
      variables, blood chemistries, electrolytes, endocrine responses, and pulmonary
      function were assessed with t-test and Chi-square analyses, P < 0.05. RESULTS: As
      compared to Non-OC users, OC users had lower progesterone levels (ng x ml(-1)) at
      SL (0.7 +/- 0.5 vs. 3.2 +/- 4.6) and at ALTD (0.7 +/- 0.7 vs. 3.1 +/- 4.6). AMS
      was significantly more prevalent in OC users (85%) as compared to Non-OC users
      (51%). Acetazolamide prophylaxis was not protective, with a greater proportion of
      OC users (100%) developing AMS despite its use as compared to Non-OC users (50%).
      Blood pressure responses also differed significantly, with OC users displaying
      higher mean arterial pressures at ALTD vs. Non-OC users. CONCLUSION: OC use at
      ALTD is associated with an increased risk for the development of AMS.
      Acetazolamide prophylaxis with OC use was also associated with an increased rate
      of AMS development.

PMID- 24279231
TI  - Hot-air balloon tours: crash epidemiology in the United States, 2000-2011.
AB  - INTRODUCTION: Hot-air balloon tours are FAR Part 91-governed balloon rides
      conducted for compensation or hire. Part 91, General Aviation, in general
      involves the least strict federal regulations and accounts for the majority of
      aviation crashes and fatalities. METHODS: National Transportation Safety Board
      reports of hot-air balloon tour crashes in the United States from 2000 through
      2011 were read and analyzed. RESULTS: During the 12-yr period, 78 hot-air balloon
      tours crashed, involving 518 occupants. There were 91 serious injuries and 5
      fatalities; 83% of crashes resulted in one or more serious or fatal outcomes. Of
      the serious injuries characterized, 56% were lower extremity fractures. Most
      crashes (81%) occurred during landing; 65% involved hard landings. Fixed object
      collisions contributed to 50% of serious injuries and all 5 fatalities. During
      landing sequences, gondola dragging, tipping, bouncing, and occupant ejection
      were associated with poor outcomes. Of the crashes resulting in serious or fatal
      outcomes, 20% of balloons were significantly damaged or destroyed. DISCUSSION:
      The incidence of morbidity and mortality is high among hot-air balloon tour
      crashes, and the proportion of balloon crashes attributed to paid rides appears
      to have increased over time. In addition to examining the role of restraint
      systems, personal protective equipment, and power line emergency procedures in
      ballooning, injury prevention efforts should target factors such hard landings,
      object strikes, gondola instability, and occupant ejections, which are associated
      with balloon injuries and deaths. Crash outcomes may also improve with vehicle
      engineering that enables balloons themselves to absorb impact forces.

PMID- 24279232
TI  - Pulse contour methods to estimate cardiovascular indices in micro- and
      hypergravity.
AB  - BACKGROUND: The importance of noninvasive health monitoring in space increased as
      a result of the long-duration missions on the International Space Station (ISS).
      In order to monitor changes in cardiovascular indices such as cardiac output (CO)
      and total peripheral resistance (TPR), many methods have been developed using
      signal processing and mathematical modeling techniques. However, their
      performance in various gravitational conditions has not been known. METHODS: The
      present study compared 10 methods to estimate CO and TPR by processing peripheral
      arterial blood pressure signals recorded from 8 subjects in multiple gravity
      levels (1 G, 0 G, and 1.8 G) during parabolic flights. For reference data sets,
      CO and TPR were simultaneously obtained by an inert gas rebreathing technique.
      Root normalized mean square errors and Bland-Altman plots were used to evaluate
      the estimation methods. RESULTS: The corrected impedance method achieved the
      lowest estimation errors (20.0% CO error and 23.5% TPR error) over the three
      gravity levels. In microgravity, mean arterial pressure was also demonstrated to
      be an indicator of CO (24.5% error). DISCUSSION: The corrected impedance method
      achieved low estimation errors for a wide range of the gravity levels. Gravity
      dependent performance was observed in the mean arterial pressure method that
      achieved low errors in the short-term 0 G.

PMID- 24279233
TI  - Emotional energy, work self-efficacy, and perceived similarity during the Mars
      520 study.
AB  - BACKGROUND: The objective of the present research was to study the dynamics of
      changes in emotional energy, work self-efficacy and perceived similarity in the
      crew of the Mars 520 experimental study. METHODS: The study comprised six
      volunteers, all men, between 27-38 yr of age (M = 32.16; SD = 4.99). The Mars 520
      experimental study simulated all the elements of the proposed Mars mission that
      could be ground simulated, i.e., traveling to Mars, orbiting it, landing, and
      returning to Earth. During the simulation, measures of emotional energy, work
      self-efficacy, and perceived similarity were repeated every month. The data were
      analyzed using linear mixed effect models. RESULTS: Emotional energy, work self
      efficacy, and perceived similarity gradually increased in the course of the
      simulation. DISCUSSION: There was no evidence for a so-called third quarter
      phenomenon (the most strenuous period of group isolation, psychologically,
      emotionally, and socially) in our data. On the contrary, work self-efficacy,
      emotional energy, and group cohesion (indexed here by the subject's perceived
      similarity to others) increased significantly in the course of the simulation,
      with the latter two variables showing positive growth in the group functioning.

PMID- 24279234
TI  - A novel lunar bed rest analogue.
AB  - INTRODUCTION: Humans will eventually return to the Moon and thus there is a need
      for a ground-based analogue to enable the study of physiological adaptations to
      lunar gravity. An important unanswered question is whether or not living on the
      lunar surface will provide adequate loading of the musculoskeletal system to
      prevent or attenuate the bone loss that is seen in microgravity. Previous
      simulations have involved tilting subjects to an approximately 9.5 degrees angle
      to achieve a lunar gravity component parallel to the long-axis of the body.
      However, subjects in these earlier simulations were not weight-bearing, and thus
      these protocols did not provide an analogue for load on the musculoskeletal
      system. METHODS: We present a novel analogue which includes the capability to
      simulate standing and sitting in a lunar loading environment. A bed oriented at a
      9.5 degrees angle was mounted on six linear bearings and was free to travel with
      one degree of freedom along rails. This allowed approximately 1/6 body weight
      loading of the feet during standing. "Lunar" sitting was also successfully
      simulated. RESULTS: A feasibility study demonstrated that the analogue was
      tolerated by subjects for 6 d of continuous bed rest and that the reaction forces
      at the feet during periods of standing were a reasonable simulation of lunar
      standing. During the 6 d, mean change in the volume of the quadriceps muscles was
      -1.6% +/- 1.7%. DISCUSSION: The proposed analogue would appear to be an
      acceptable simulation of lunar gravity and deserves further exploration in
      studies of longer duration.

PMID- 24279235
TI  - Rehabilitation from airsickness in military pilots: long-term treatment
      effectiveness.
AB  - BACKGROUND: Airsickness (AS) still represents a major issue in aviation medicine
      and affects many student pilots and aircrew members. This study aimed at
      producing an update of the Italian Air Force rehabilitation program for AS,
      including data on a prolonged follow-up (> 8 yr). METHODS: Data from 20 military
      pilots with a past history of rehabilitation for incapacitating AS were compared
      to those of 65 normal controls. All individuals from both samples were
      categorized as dropouts or successfully employed in fast jets, multiengine air
      carriers, or helicopters. All AS individuals were analyzed before and after their
      treatment with the Coriolis Stress test (CST). RESULTS: The AS sample showed
      similar results with respect to the control group, with the same incidence of
      dropouts (15% vs. 14%) and destination to rotary wing flight lines (15% vs. 17%).
      All dropouts were observed within the first year after rehabilitation. A
      statistically non-significant trend of being employed in transport aircraft (50%
      of individuals vs. 34% in the control group) rather than in fast jets (20% vs.
      35%) was observed in the AS sample. DISCUSSION: Within the AS sample, the
      rehabilitation protocol had a success rate of 85%. The effects of rehabilitation
      were long lasting (mean follow up: 8.3 +/- 2.5 yr). Moreover, the flight career
      of AS treated individuals did not significantly differ from controls. The
      pretreatment CST was helpful in calibrating the initial intensity and duration of
      the nauseogenic stimulation, while it was useless as a post-treatment analysis of
      the outcome from training.

PMID- 24279236
TI  - Traumatic carotid artery dissection during acrobatic flight associated with -G(z)
      acceleration.
AB  - BACKGROUND: A 38-yr-old man developed the acute onset of expressive aphasia and
      right hemiparesis during the performance of an advanced aerobatic flight
      maneuver. CASE REPORT: Magnetic resonance imaging (MRI) demonstrated patchy
      infarction in the territory of the left middle cerebral artery. Magnetic
      resonance, angiography (MRA) revealed a dissection of the left internal carotid
      artery. He had flown an aerobatic routine with multiple abrupt transitions from
      +8 G(z) to -6 G(z) 4 d prior with no ill effects. He had no risk factors for
      dissection or stroke. The patient recovered full neurological function within
      several hours. DISCUSSION: We propose that the arterial dissection occurred
      during the patient's preceding aerobatic flight, leading to an embolic stroke 4 d
      later. The most likely mechanism was sustained -G(z) acceleration combined with
      flexion and rotation of his neck during abrupt transition from +G(z) to -G(z),
      causing stretching of the internal carotid artery at the point of entry to the
      skull base and development of an intimal tear.

PMID- 24279237
TI  - Decelerations and muscle responses during parachute opening shock.
AB  - INTRODUCTION: Pain in the neck region among skydivers can be related to repeated
      parachute opening shocks (POS), but empirical data on ramair POS biomechanics is
      lacking in the literature. The aim of this study was to develop and evaluate a
      methodology for assessment of multidirectional accelerations and neck muscle
      activity during parachuting, and to describe preliminary data. METHODS: In an
      experimental design, four experienced skydivers made two consecutive skydives.
      Deceleration was recorded with two triaxial accelerometers, one placed on the
      skydiver's cervicothoracic junction (acc-neck) and the other on the harness (acc
      rig). Surface electromyography (EMG) was sampled from four sites bilaterally:
      anterior-neck, posterior upper and lower neck, and upper shoulder muscles. EMG
      activity was normalized against a premeasured maximum voluntarily produced
      electrical signal (MVE). RESULTS: The measuring equipment did not interfere with
      the parachute jumps. High-quality signals were recorded. The median peak POS
      deceleration for the acc-neck vs. acc-rig indicated differences (4.0 G vs. 5.1
      G), in addition to significant differences emerging for medians of average and
      maximum onset rates of deceleration (avg: 1.2 G x s(-1) vs. 19.5 G x s(-1); max:
      23.0 G x s(-1) vs. 80.0 G x s(-1)). The median of overall muscleactivity was as
      high as 87% MVE, but no differences in peak activity were found between muscles.
      Temporal activations of the posterior upper neck occurred less than 50 ms after
      deceleration initiation, indicating feedforward control of the neck. CONCLUSION:
      All instruments recorded data of good quality without impeding the skydiving
      activity. Triaxial accelerometry on the neck vs. the harness yielded dissimilar
      results, underlining the importance of correct accelerometer placement. Muscle
      activity was high during POS and neck muscles showed anticipatory tendencies.

PMID- 24279238
TI  - Spatial disorientation: more than just illusion.
AB  - Despite aggressive efforts in spatial disorientation (SD) research, hardware
      development, and training, the operational impact of SD in terms of crew and
      aircraft losses remains significant. Current training in spatial orientation is
      primarily composed of didactic lectures on the anatomy and physiology of the
      sensory systems. Significant efforts have been concentrated on reproducing
      various types of visual and vestibular "illusions" that pilots might encounter in
      flight, with limited and varying success. Unfortunately, the terms of "SD" and
      "illusion" have been used synonymously, leading to the general belief that if one
      were to be exposed to a specific type of illusion, one can prevent or avoid SD
      mishaps. Another setback is the inability of ground-based devices to reproduce
      the flight envelope. Often the demonstration of a specific illusion ends abruptly
      without further explanation or how these illusions can affect pilot performance.
      Demonstration of illusions seldom deals with the precipitating factors. We should
      provide pilots with skills to anticipate and assess the risk of SD during mission
      planning. Pilots should be sensitized to the physical and mental performance
      decrement during sensory conflicts and inadequacies. Recommendations should also
      be made on possible ways to recover from SD should they become disoriented.
      Special attention should be drawn to the properties of various flight displays
      that may contribute to SD. G tolerance and disorientation should be examined
      together in high performance aircraft as there is a close relationship between
      exposure to acceleration and maintaining orientation. The motto for counteracting
      SD is: anticipate, avoid, and counteract SD.

PMID- 24279239
TI  - New genetic technology may help pilots, aviation employees, and color vision
      researchers.

PMID- 24279240
TI  - You're the flight surgeon: decompression illness.

PMID- 24279241
TI  - This month in aerospace medicine history.

PMID- 24279242
TI  - Higher learning.

PMID- 24279243
TI  - Changing the game.

PMID- 24279244
TI  - Confounding.

PMID- 24279245
TI  - Students on move.

PMID- 24279246
TI  - The gap between clinical practice and education.

PMID- 24279247
TI  - Nurses of world united.

PMID- 24279248
TI  - Millennials-the new normal.

PMID- 24279249
TI  - Tapping into her power.

PMID- 24279250
TI  - [Diagnostic approach and treatment of immune thrombocytopenia in adults].
AB  - The aim of this review is to provide the Croatian medical public with novel
      insights into the definition, pathogenesis, diagnostic algorithms and treatment
      approaches to immune thrombocytopenia (ITP) in adults. Recently, primary ITP has
      been uniformly defined as an autoimmune disorder characterized by an isolated
      platelet count lower than 100 x 10(9)/L without preexisting disease or
      conditions, which could lead to thrombocytopenia. The recognition of primary and
      secondary ITP is important because they require different treatment strategies.
      In secondary ITP, therapeutic approach oriented towards the underlying disorder.
      Unlike childhood onset ITP, which is a self-limited condition with high rates of
      spontaneous remissions, adulthood onset ITP usually has chronic course.
      Previously, the pathogenesis of ITP was considered to be immune mediated
      destruction of platelets in liver and spleen, while recent findings have shown a
      novel pathophysiological pathway based on the inhibition of thrombopoiesis,
      leading to novel treatment approaches. The diagnosis of ITP is based on exclusion
      of the possible underlying causes of thrombocytopenia and consists of simple
      diagnostic procedures. The decision to treat ITP should be based individually:
      platelets count (lower than 30 x 10(9)/L), various bleeding risk factors and
      patient's preference. The use of corticosteroids is the mainstay of first line
      therapy. Two most commonly used corticosteroids are prednisone and dexamethasone.
      Prednisone is administered continuously, while dexamethasone is applied in
      cycles. Due to the lack of randomized clinical trials, it is not possible to
      recommend certain class of corticosteroid therapy. Another two agents used as
      first line therapy in case of corticosteroid refractoriness or the need of rapid
      platelet elevation, are intravenous immunoglobulins and anti-D immunoglobulin
      (anti-D is not approved in Europe). They are characterized by rapid onset of
      platelet recovery and low long-term remission rates. Until recently, splenectomy,
      with adequate infectious and thromboprophylaxis, was the therapy of choice in
      patients who did not respond to corticosteroids due to high long-term remission
      rates and low relapse rates. This procedure can be offered to a younger patient
      without significant comorbidities after the first year of ITP duration. With
      advances in the understanding of ITP pathogenesis, a new class of drug has been
      established: thrombopoietin agonists (TPO). Eltrombopag and romiplostim, the TPO
      agonists currently approved for the management of ITP in patients who failed the
      first line therapy and are not suitable for splenectomy, are only two agents that
      have shown benefits in large clinical randomized trials. They are characterized
      by a high response rate and appropriate safety profile, but the need for
      continuous use, a high relapse rate after therapy withdrawal, and price limit
      their use in everyday practice. TPO agonists represent an appropriate treatment
      choice in patients who have relapse after splenectomy. Another agent, often used
      in everyday clinical practice, is rituximab with high response and relapse rates.
      Its use is based on small studies, and due to the lack of clinical randomized
      controlled trials, rituximab is not approved by the leading medical agencies for
      this indication. As shown in this review article, our understanding and therapy
      for ITP has improved, but further research is needed to implement evidence-based
      therapy in clinical practice.

PMID- 24279251
TI  - [Quality of life in patients with heart failure].
AB  - OBJECTIVE: The objective of this work was to determine the quality of life in
      patients with heart failure using the SF-36 and Minnesota questionnaire and to
      determine the importance of applying Framingham criteria as predictors of the
      value of these questionnaires. PATIENTS AND METHODS: This cross-sectional study
      analyzed the quality of life in 120 subjects of both sexes and all age groups
      suffering from heart failure, according to the severity of clinical presentation.
      Subjects were divided into 4 equal groups according to NYHA classification of
      heart failure. Selection of subjects was made using the Framingham criteria for
      confirming already diagnosed heart failure. Control group included 30 patients
      not suffering from heart failure. Quality of life was assessed by use of the SF
      36 and Minnesota questionnaire. RESULTS: In the study population of 150 subjects,
      there were 76 (51%) male and 74 (49%) female subjects divided into 4 NYHA groups
      of 30 subjects (20.0%) and control group of 30 subjects (20.0%). The analysis of
      within-group sex representation yielded no statistically significant difference
      (chi2 = 1.70, df = 4; p = 0.79). There was no statistically significant between
      group age difference either (ANOVA, F = 0.74; p = 0.57). The values of SF-36 and
      Minnesota score expressed as median in the control and 4 NYHA groups were 98.6,
      90.76, 70.14, 36.45 and 25.41 (Ht = 116.84; p < 0.0001) and 0.0, 0.47, 1.64, 2.99
      and 3.42 (Ht = 113.42; p < 0.0001), respectively. The correlation coefficient r
      between heart failure NYHA classes expressed in the values of SF-36 and Minnesota
      score was r = -0950; p < 0.0001 and r = 0.931; p < 0.0001, respectively. The
      correlation coefficient r between the number of major and minor Framingham
      criteria and the values of SF-36 and Minnesota score was r = -0.790, -0.660; p <
      0.0001 and r = 0.774, 0.671; p < 0.0001, respectively. CONCLUSION: The findings
      suggested that the quality of life in patients with heart failure was impaired
      and associated with the severity of clinical presentation, and that Framingham
      criteria could serve as significant predictors of the value of SF-36 and
      Minnesota scores and quality of life in patients with heart failure.

PMID- 24279252
TI  - ["Early patient contact"--the split model].
AB  - In the 2011/2012 academic year, School of Medicine in Split introduced the
      subject Clinical and Social Skills for 1st and 2nd year students. During the 25
      hours of the 85-hour class, the students spent time in their mentors' general
      practice offices and made home visits with nurses. The goal of the introduction
      of this subject was to enable students to meet patients and their surroundings
      early in their studies; we believed that this would contribute to increased
      respect towards the profession and better absorption of communication skills, as
      well as better understanding of the patients and additional motivation to
      complete their studies. At the end of five-day class, the students wrote down
      their impressions, revealing that they had adjusted well to this form of the
      class, and that their expectations were fulfilled. They noticed the value of high
      quality communication between the doctor and the patient, gained confidence, and
      felt more motivated to continue studying. They rated the class as useful and
      necessary, recommending it to last longer.

PMID- 24279253
TI  - [Socioeconomic status and risky health behaviors in Croatian adult population].
AB  - INTRODUCTION AND AIM: Based on the previous research, there is strong association
      between low socioeconomic status (SES) and high morbidity and mortality rates.
      Even though association between SES and risky health behaviors as the main
      factors influencing health has been investigated in Croatian population, some
      questions are yet to be answered. The aim of this study was to investigate the
      presence of unhealthy diet, physical inactivity, smoking and excessive drinking
      in low, middle, and high socioeconomic group of adult Croatian population
      included in the cohort study on regionalism of cardiovascular health risk
      behaviors. We also investigated the association between SES measured by income,
      education and occupation, as well as single SES indicators, and risky health
      behaviors. SAMPLE AND METHODS: We analyzed data on 1227 adult men and women (aged
      19 and older at baseline) with complete data on health behaviors, SES and chronic
      diseases at baseline (2003) and 5-year follow up. Respondents were classified as
      being healthy or chronically ill. SES categories were derived from answers to
      questions on monthly household income, occupation and education by using two-step
      cluster analysis algorithm. RESULTS: At baseline, for the whole sample as well as
      for healthy respondents, SES was statistically significantly associated with
      unhealthy diet (whole sample/healthy respondents: p = 0.001), physical inactivity
      (whole sample/healthy respondents p = 0.44/ p = 0.007), and smoking (whole
      sample/healthy respondents p < 0.001/p = 0.002). The proportion of respondents
      with unhealthy diet was greatest in the lowest social class, smokers in the
      middle and physically inactive in the high social class. During the follow up,
      smoking and physical inactivity remained statistically significantly associated
      with SES. In chronically ill respondents, only smoking was statistically
      significantly associated with SES, at baseline and follow up (p = 0.001/p =
      0.002). The highest share of smokers was in the middle social class. DISCUSSION
      AND CONCLUSION: Results of our study show that risky health behaviors are
      associated with SES and are divergently represented across socioeconomic groups
      of adult Croatian population. There is an obvious need for interventions
      targeting the specific socioeconomic group and behavior characteristic of that
      group.

PMID- 24279254
TI  - [Geometry of the hip joint: methodology and guidelines].
AB  - An hip fracture is an significant personal, family and health issue of people
      older than 65 years. In the first year of the fracture up to 30% of the injured
      die and about 50% of them never regain their formal degree of independence in
      fulfilling day-to-day activities. Estimations are that throughout 30 years in the
      world there will be around 6 million hip fractures per year which is about four
      times the todays amount. Todays predictions of hip fractures based on the hip
      geometry have shown us that the hip geometry is an independent variable of the
      bone mineral density. The hip geometry is more resistant to the effect of various
      factors than the bone mineral density and the changes throu life are a lot
      slower. The uniqueness and the sensitivity of the hip geometry in predicting a
      fracture is high and acceptable in research results of most authors. In this
      review we present the previous relevant knowledge about the measures and factors
      which determines the hip geometry and the accepted amount of pictorial methods of
      hip display. We have compared the methodology and the patients of eleven randomly
      picked writings on predicting hip fracture based on the hip geometry. We
      highlight the need of further refinement of the methodology and the more balanced
      selection of patients for a greater conformity in future writings. The hip
      geometry has shown it self as an useful diagnostical instrument but there is
      still more room for its improvement.

PMID- 24279255
TI  - [Prognostic value of ophthalmic artery color Doppler sonography for progression
      to glaucoma in vitiligo patients].
AB  - The aim of this study was to assess the prognostic value, i.e. the role of
      hemodynamic changes in the ophthalmic artery determined by color Doppler imaging
      in patients with vitiligo in relation to the occurrence of primary open-angle
      glaucoma (POAG), and to call attention to the importance of examination of the
      vascular component in routine examinations of patients by clinical dermatologists
      and ophthalmologists, due to the possible correlation of vitiligo and
      ophthalmologic changes indicating POAG. Clinical observations and research have
      shown that patients treated for vitiligo are often diagnosed with POAG or have
      confirmed diagnosis in their medical history. These findings motivated the
      research of the vascular component as a possible correlation between vitiligo and
      POAG. The vascular component of POAG and its role in the dynamics of glaucoma
      progression has not been fully explained and is still somewhat controversial, and
      the resulting ischemic disorders are primarily related to optical nerve damage.
      During the course of a continuous two-year research started in March 2008 and
      completed in March 2010, a total of 42 patients with vitiligo were examined in
      the specialist dermatovenereology unit of the Department of Skin Diseases and
      Sexually Transmitted Diseases. Following clinical examination and Wood's lamp
      examination, patients with suspected glaucoma were referred to the glaucoma unit
      of the Department of Ophthalmology to detect or check the progression of POAG. At
      the Department of Internal Medicine, Split University Hospital Center, color
      Doppler imaging of ophthalmic artery was performed in all patients on both eyes
      to examine its hemodynamics. All study participants underwent complete
      ophthalmologic examination: visual acuity, fundus of the eye, eye pressure
      measurement, anterior eye segment biomicroscopy with gonioscopy and visual field.
      In conclusion, our study showed color Doppler imaging and investigation of
      vascular parameters in ophthalmic artery to provide an insight into the vascular
      function in differential analysis and can be determined as a correlation or
      potential risk factor related to vitiligo and POAG. For this reason, we suggest
      that patients treated for vitiligo, irrespective of their age, sex, affected
      area, localization and duration of the disease, should regularly undergo complete
      ophthalmologic examination with special emphasis on POAG diagnosis. Considering
      the relatively limited sample and trial period, we can already substantiate and
      confirm that the correlation is not random. Future research in a larger number of
      vitiligo and POAG patients should provide definitive answer concerning
      correlation between the two diseases and lead to final conclusion, along with
      investigation of other hematologic factors related to blood hypercoagulability in
      order to reach better understanding of the vascular component function.

PMID- 24279256
TI  - [Necrotizing fasciitis of the neck].
AB  - Necrotizing fasciitis is a rare and rapidly progressive infection characterized
      by necrosis of the superficial fascia and spread on the surrounding skin or
      muscles, which can be fatal. It usually occurs in the limbs, abdominal wall and
      perineum. In this retrospective review, the authors present 15 patients with
      cervical necrotizing fasciitis. The patient mean age was 54.7 years and they had
      one or more comorbid health problems. Five of them had descending necrotizing
      mediastinitis and three had progressive sepsis with toxic shock syndrome. Broad
      spectrum intravenous antibiotic therapy was administered to all patients
      immediately, and in three of them we used five-day intravenous immunoglobulin
      therapy for the signs of toxic shock syndrome. After positive computed tomography
      imaging for necrotizing fasciitis, we used surgical exploration and debridement
      of necrotic tissue. In five patients, the initial surgery also included
      mediastinal transcervical drainage. Preoperative tracheotomy was performed in six
      patients and delayed tracheotomy in one patient. Histopathologically, all cases
      showed extensive necrosis of debrided fascia and vascular thrombosis of the neck
      soft tissue. The mortality rate was 6.7% (1/15). The authors point to the
      importance of early diagnosis and timely surgical management, broad-spectrum
      antibiotics and intravenous immunoglobulin therapy when patients are too unstable
      to undergo surgery.

PMID- 24279257
TI  - [Mast cell leukemia--case report].
AB  - Mast cell leukemia is extremely rare, more often arises de novo and in 15% of
      cases developes from preexistence mast cell diseases. It is a high malignant
      leukemia with bad prognosis and a short survival. A 72-year old female was
      admitted to hospital with clinically suspected plasmocytoma. She had eccematoid
      changes on her trunk and underarms. Radiogramm showed osteolytic lesions of the
      right thigh and pelvis. FNA of the bone marrow revealed hypercellular smear with
      80% of mast cells and immature mast cells which were cytochemically positive to
      toluidin (Figure 1. and 2.), chloracetate, alcian blue, acid fosphatase and Sudan
      black and negative to periodic acid Schiff (PAS) and peroxidase (POX). The
      peripheral blood smear showed single mast cells which were positive to toluidin.
      The bone marrow biopsy confirmed mast cell leukemia. The chariogramm of the bone
      marrow showed numerical and structural chromosomal changes. Two month after the
      diagnosis the patient suffered from right thigh fracture and was treated with
      local radiotherapy, antihistaminic and analgetic therapy. The patient died within
      6 month after the diagnosis. CONCLUSION: Mast cell leukemia is very rare and high
      grade leukemia with short survival time. Cytological diagnosis is possible, when
      there is more then 20% of atypical mast cells in the bone marrow aspirate. The
      diagnosis of aleukemic variant of mast cell leukemia could be stated if there is
      less then 10% of mast cells in the peripheral blood.

PMID- 24279258
TI  - [Meckel's diverticulitis in the early postoperative course after appendectomy].
AB  - Meckel's diverticulum is the most frequent anomaly of the small intestine that
      results from the failure of the vitelline duct to obliterate during the
      gestation. It occurs on the antimesenteric border of the ileum, usually 60-80 cm
      proximally to the ileocecal valve. Meckel's diverticulum is true diverticulum
      because it has all the three layers of the terminal ileum. The heterotopic mucosa
      is most commonly gastric or pancreatic. Most patients are asymptomatic. Meckel's
      diverticulum is most frequently diagnosed as an incidental finding during
      laparotomy. The most frequent complications of Meckel's diverticulum are
      intestinal obstruction, rectal bleeding, diverticulitis and perforation due to
      peptic ulcer. Surgical resection is the treatment of choice for symptomatic
      Meckel's diverticulum.

PMID- 24279259
TI  - Leaf traits within communities: context may affect the mapping of traits to
      function.
AB  - The leaf economics spectrum (LES) has revolutionized the way many ecologists
      think about quantifying plant ecological trade-offs. In particular, the LES has
      connected a clear functional trade-off (long-lived leaves with slow carbon
      capture vs. short-lived leaves with fast carbon capture) to a handful of easily
      measured leaf traits. Building on this work, community ecologists are now able to
      quickly assess species carbon-capture strategies, which may have implications for
      community-level patterns such as competition or succession. However, there are a
      number of steps in this logic that require careful examination, and a potential
      danger arises when interpreting leaf-trait variation among species within
      communities where trait relationships are weak. Using data from 22 diverse
      communities, we show that relationships among three common functional traits
      (photosynthetic rate, leaf nitrogen concentration per mass, leaf mass per area)
      are weak in communities with low variation in leaf life span (LLS), especially
      communities dominated by herbaceous or deciduous woody species. However, globally
      there are few LLS data sets for communities dominated by herbaceous or deciduous
      species, and more data are needed to confirm this pattern. The context-dependent
      nature of trait relationships at the community level suggests that leaf-trait
      variation within communities, especially those dominated by herbaceous and
      deciduous woody species, should be interpreted with caution.

PMID- 24279260
TI  - Beta diversity of marine bacteria depends on temporal scale.
AB  - Factors controlling the spatial distribution of bacterial diversity have been
      intensely studied, whereas less is known about temporal changes. To address this,
      we tested whether the mechanisms that underlie bacterial temporal beta-diversity
      vary across different scales in three marine microbial communities. While
      seasonal turnover was detected, at least 73% of the community variation occurred
      at intra-seasonal temporal scales, suggesting that episodic events are important
      in structuring marine microbial communities. In addition, turnover at different
      temporal scales appeared to be driven by different factors. Intra-seasonal
      turnover was significantly correlated to environmental variables such as
      phosphate and silicate concentrations, while seasonal and interannual turnover
      were related to nitrate concentration and temporal distance. We observed a strong
      link between the magnitude of environmental variation and bacterial beta
      diversity in different communities. Analogous to spatial biogeography, we found
      different rates of community changes across temporal scales.

PMID- 24279261
TI  - Estimating extinction from species--area relationships: why the numbers do not
      add up.
AB  - Researchers commonly use species-area relationships (SAR) to estimate extinction
      rates caused by habitat loss by reversing the SAR, extrapolating backward from
      area to calculate expected species loss. We have previously shown that the
      backward SAR method considerably overestimates extinction rates due to a
      previously unrecognized sampling artifact. Jacob Bock Axelsen, Uri Roll, Lewi
      Stone, and Andrew Solow recently argued that the backward SAR method is correct
      and the method does not overestimate extinction rates. In this paper, we further
      elaborate and clarify our previous results. We show that the backward SAR method
      gives the correct extinction rate only under a strict complementary-area sampling
      design, which is not used in practice because it requires knowing which species
      are endemic to the area of destroyed habitat, or the number of species in the
      complementary area. Because of this problem, researchers substitute a power-law
      model for the SAR in the backward SAR equation. However, this substitution
      violates the backward SAR method's requirement for complementary sampling. With
      this model substitution, the backward SAR equation is no longer correct, except
      in the special case of randomly distributed species. For the complementary
      sampling or random distribution of species, the first individual of a species to
      be encountered and the last individual to be encountered to lose the species are
      exchangeable (or the same individual). But this is not the case for other
      sampling designs or if species are not randomly distributed and explains why the
      backward SAR method fails to correctly estimate extinction rates. Our proofs and
      results are general and explain the widely recognized overestimation of
      extinction by the backward SAR method. We suggest future directions for
      developing general theory for estimating species extinction from species-area
      relationships. Until then, however, the backward SAR method should not be used to
      estimate species extinction in practice.

PMID- 24279262
TI  - To mix or not to mix: comparing the predictive performance of mixture models vs.
      separate species distribution models.
AB  - Species distribution models (SDMs) are an important tool for studying the
      patterns of species across environmental and geographic space. For community
      data, a common approach involves fitting an SDM to each species separately,
      although the large number of models makes interpretation difficult and fails to
      exploit any similarities between individual species responses. A recently
      proposed alternative that can potentially overcome these difficulties is species
      archetype models (SAMs), a model-based approach that clusters species based on
      their environmental response. In this paper, we compare the predictive
      performance of SAMs against separate SDMs using a number of multi-species data
      sets. Results show that SAMs improve model accuracy and discriminatory capacity
      compared to separate SDMs. This is achieved by borrowing strength from common
      species having higher information content. Moreover, the improvement increases as
      the species become rarer.

PMID- 24279263
TI  - Quantitative gradient of subsidies reveals a threshold in community-level trophic
      cascades.
AB  - Evidence varies on how subsidies affect trophic cascades within recipient food
      webs. This could be due to complex nonlinearities being masked by single-level
      manipulations (presence/absence) of subsidies in past studies. We predicted that
      trophic cascade strength would increase nonlinearly across a gradient of
      subsidies. We set out to reveal these complex, nonlinear relationships through
      manipulating a quantitative gradient of detrital subsidies to lake benthic food
      webs along with the presence/absence of trout. Contrary to our prediction, we
      found that trophic cascades only occurred at low subsidy levels, disappearing as
      subsidies increased. This threshold in trophic cascade strength may be due to an
      increase in intermediate predators in the absence of top predators, as well as
      changes in the proportion of armored vs. un-armored primary consumers. Future
      studies on the effect of subsidies on trophic cascade strength need to
      incorporate naturally occurring gradients to reveal the complex direct and
      indirect interactions within food webs.

PMID- 24279264
TI  - Morphological traits and density of foundation species modulate a facilitation
      cascade in Australian mangroves.
AB  - Facilitation cascades are critical to the maintenance of biodiversity in a
      variety of habitats. Through a series of two experiments, we examined how the
      morphological traits and density of interacting foundation species influence the
      establishment and persistence of a facilitation cascade in temperate Australian
      mangrove forests. In this system, mangrove pneumatophores trap the free-living
      alga, Hormosira banksii, which, in turn, supports dense and diverse assemblages
      of epifaunal mollusks. The first experiment, which manipulated pneumatophore
      height and density, revealed that these two traits each had additive negative
      effects on the establishment, but additive positive effects on the persistence of
      the cascade. High densities of tall pneumatophores initially served as a physical
      barrier to algal colonization of pneumatophore plots, but over the longer-term
      enhanced the retention of algae. The increased algal biomass, in turn,
      facilitating epifaunal colonization. The second experiment demonstrated that the
      retention of algae by pneumatophores was influenced more by algal thallus length
      than vesicle diameter, and this effect occurred independent of pneumatophore
      height. Our study has extended facilitation theory by showing that the
      morphological traits and density of basal and intermediary facilitators influence
      both the establishment and persistence of facilitation cascades. Hence, attempts
      to use foundation species as a tool for restoration will require an understanding
      not only of the interactions among these, but also of the key traits that modify
      interrelationships.

PMID- 24279265
TI  - An invasive species facilitates the recovery of salt marsh ecosystems on Cape
      Cod.
AB  - With global increases in human impacts, invasive species have become a major
      threat to ecosystems worldwide. While they have been traditionally viewed as
      harmful, invasive species may facilitate the restoration of degraded ecosystems
      outside their native ranges. In New England (USA) overfishing has depleted salt
      marsh predators, allowing the herbivorous crab Sesarma reticulatum to denude
      hundreds of hectares of low marsh. Here, using multiple site surveys and field
      caging experiments, we show that the subsequent invasion of green crabs, Carcinus
      maenas, into heavily burrowed marshes partially reverses decades of cordgrass die
      off. By consuming Sesarma, eliciting a nonlethal escape response, and evicting
      Sesarma from burrows, Carcinus reduces Sesarma herbivory and promotes cordgrass
      recovery. These results suggest that invasive species can contribute to restoring
      degraded ecosystems and underscores the potential for invasive species to return
      ecological functions lost to human impacts.

PMID- 24279266
TI  - Realistic changes in seaweed biodiversity affect multiple ecosystem functions on
      a rocky shore.
AB  - Given current threats to biodiversity, understanding the effects of diversity
      changes on the functions and services associated with intact ecosystems is of
      paramount importance. However, limited realism in most biodiversity studies makes
      it difficult to link the large and growing body of evidence for important
      functional consequences of biodiversity change to real-world losses of
      biodiversity. Here, we explored two methods of incorporating realism into
      biodiversity research: (1) the use of two-, five-, and eight-species assemblages
      that mimicked those that we observed in surveys of seaweed biodiversity patterns
      on a northern California (USA) rocky shore and the explicit comparison of those
      assemblages to random assemblages compiled from the same local species pool; and
      (2) the measurement of two fundamental ecosystem functions, nitrate uptake and
      photosynthesis, both of which contribute to growth of primary producers.
      Specifically, we measured nitrate uptake rates of seaweed assemblages as a
      function of initial nitrate concentrations and photosynthetic rates as a function
      of irradiance levels for both realistic and random assemblages of seaweeds. We
      only observed changes in ecosystem functioning along a richness gradient for
      realistic assemblages, and both maximum nitrate uptake rates (V(max)) and
      photosynthetic light use efficiency values (alpha(p) = P(max)/I(K)) were higher
      in realistic assemblages than in random assemblages. Furthermore, the parameter
      affected by changes in richness depended on the function being measured. Both
      V(max) and alpha(p) declined with increasing richness in nonrandom assemblages
      due to a combination of species identity effects (for V(max) and overyielding
      effects (for both V(max) and alpha(p)). In contrast, neither nitrate uptake
      efficiency values (alpha(N) = V(max)/K(s)), nor maximum photosynthetic rates
      (Pmax) changed along the gradient in seaweed species richness. Furthermore,
      overyielding was only evident in realistic assemblages, and the parameters
      exhibiting overyielding, including V(max), alpha(N), P(max), and alpha(p),
      changed along a gradient in species richness. Our results suggest that in
      realistic assemblages of species (1) some functions may be maximized at low
      levels of species richness, and (2) it is not only diversity, per se, that is
      important for sustaining multiple ecosystem functions, but also the range of
      diversity values in an ecosystem.

PMID- 24279267
TI  - Genetic and experimental evidence for a mixed-age, mixed-origin bank of kelp
      microscopic stages in southern California.
AB  - Laboratory studies have demonstrated that the microscopic stages of kelps can
      rapidly resume development from a delayed state. Like terrestrial seeds or
      aquatic resting eggs, banks of delayed kelp stages may supplement population
      recovery after periods of stress, playing an important role for kelp populations
      that experience adult sporophyte absences due to seasonal or interannual
      disturbances. We found that removing the microscopic stages from natural rock
      substratum could prevent the appearance of juvenile kelp sporophytes for three
      months and the establishment of a diverse kelp assemblage for over four months
      within a southern California kelp forest. Juveniles were observed within one
      month in plots where microscopic stages were left intact, which may confer an
      advantage for the resulting sporophytes as they attain larger sizes before later
      recruiting neighbors. Microsatellite diversity was high (expected heterozygosity
      HE approximately 0.9) for juveniles and adults within our sites. Using a
      microsatellite-based parentage analysis for the dominant kelp, Macrocystis
      pyrifera, we estimated that a portion of the new M. pyrifera sporophyte recruits
      had originated from their parents at least seven months after their parents had
      disappeared. Similar delay durations have been demonstrated in recent laboratory
      studies. Additionally, our results suggest that zoospore dispersal distances > 50
      m may be supported by including additional microsatellite loci in the analysis.
      We propose a mixed-age and, potentially, a mixed-origin bank of M. pyrifera
      gametophytes promotes maximal genetic diversity in recovering populations and
      reduces population genetic subdivision and self-fertilization rates for intact
      populations by promoting the survival of zoospores dispersed > 10 m and during
      inhospitable environmental conditions.

PMID- 24279268
TI  - Large birth size does not reduce negative latent effects of harsh environments
      across life stages in two coral species.
AB  - When juveniles must tolerate harsh environments early in life, the
      disproportionate success of certain phenotypes across multiple early life stages
      will dramatically influence adult community composition and dynamics. In many
      species, large offspring have a higher tolerance for stressful environments than
      do smaller conspecifics (parental effects). However, we have a poor understanding
      of whether the benefits of increased parental investment carry over after
      juveniles escape harsh environments or progress to later life stages (latent
      effects). To investigate whether parental effects and latent effects
      interactively influence offspring success, we determined the degree to which
      latent effects of harsh abiotic conditions are mediated by offspring size in two
      stony coral species. Larvae of both species were sorted by size class and exposed
      to relatively high-temperature or low-salinity conditions. Survivorship was
      quantified for six days in these stressful environments, after which surviving
      larvae were placed in ambient conditions and evaluated for their ability to
      settle and metamorphose. We subsequently assessed long-term post-settlement
      survival of one species in its natural environment. Following existing theory, we
      expected that, within and between species, larger offspring would have a higher
      tolerance for harsh environmental conditions than smaller offspring. We found
      that large size did enhance offspring performance in each species. However, large
      offspring size within a species did not reduce the proportional, negative latent
      effects of harsh larval environments. Furthermore, the coral species that
      produces larger offspring was more, not less, prone to negative latent effects.
      We conclude that, within species, large offspring size does not increase
      resistance to latent effects. Comparing between species, we conclude that larger
      offspring size does not inherently confer greater robustness, and we instead
      propose that other life history characteristics such as larval duration better
      predict the tolerance of offspring to harsh and variable abiotic conditions.
      Additionally, when considering how stressful environments influence offspring
      performance, studies that only evaluate direct effects may miss crucial
      downstream (latent) effects on juveniles that have significant consequences for
      long-term population dynamics.

PMID- 24279269
TI  - Biodiversity effects of ecosystem engineers are stronger on more complex
      ecosystem processes.
AB  - The relative importance of species richness and identity for the diversity
      function relationship remains controversial. We mechanistically explored the
      potential contribution of ecosystem processes complexity (EPC; i.e., the number
      of pathways and mechanisms through which an ecosystem process can be directly
      and/or indirectly affected by species and/or their interactions) to the
      resolution of this controversy. We hypothesized that the complementarity effects
      of biodiversity will be stronger and that the diversity-function relationship
      will be more dependent on species richness as the EPC increases. Using a benthic
      bioturbator community as a model system we tested these predictions across
      ecosystem processes that could be ordered according to their complexity
      (suspended material flux < PO4-P flux < NH4-N flux < bacterioplankton
      production). Consistent with our predictions, species richness explained an
      increasing proportion of data variation as EPC increased, whereas the contrary
      was observed for species composition. Nontransgressive overyielding was not
      affected by EPC, but the magnitude of transgressive overyielding increased
      significantly with EPC, indicating that complementarity may be stronger as EPC
      increases. Our results highlight the importance of considering the interactive
      role of the characteristics of ecosystem processes in our theoretical
      understanding of the diversity-function relationship and its underlying
      mechanisms.

PMID- 24279270
TI  - Pattern without bias: local-regional richness relationship revisited.
AB  - For decades, ecologists have been testing for species saturation by using
      regression analysis to determine the relationship between local and regional
      species richness. The cumulative result of scores of studies and meta-analyses
      has led to a general consensus that evidence of species saturation is relatively
      uncommon. However, the bias induced on the regression by the arbitrary choice of
      local and regional area has threatened to undermine this consensus and has even
      led to the proposal to abandon the regression method entirely. Nonetheless, the
      use of regression analysis to determine local-regional richness relationships
      continues. We performed a meta-analysis of almost 100 data sets using a log-ratio
      based regression model that is free of the scale-induced bias inherent in more
      commonly used models. This reanalysis contradicts the general consensus:
      saturated relationships are at least as common as unsaturated patterns. However,
      a discouragingly large proportion of studies produce no discernable patterns at
      all. An explanation for such a plethora of species saturation patterns poses a
      challenge to our understanding of the processes that govern community assembly.

PMID- 24279271
TI  - Stochastic processes dominate during boreal bryophyte community assembly.
AB  - Why are plant species found in certain locations and not in others? The study of
      community assembly rules has attempted to answer this question, and many studies
      articulate the historic dichotomy of deterministic (predictable niches) vs.
      stochastic (random or semi-random processes). The study of successional sequences
      to determine whether they converge, as would be expected by deterministic theory,
      or diverge, as stochastic theory would suggest, has been one method used to
      investigate this question. In this article we ask the question: Do similar boreal
      bryophyte communities develop in the similar habitat created by convergent
      succession after fires of different severities? Or do the stochastic processes
      generated by fires of different severity lead to different communities?
      Specifically we predict that deterministic structure will be more important for
      large forest-floor species than stochastic processes, and that the inverse will
      be true for small bryophyte species. We used multivariate regression trees and
      model selection to determine the relative weight of structure (forest structure,
      substrates, soil structure) and processes (fire severity) for two groups of
      bryophyte species sampled in 12 sites (seven high-severity and five low-severity
      fires). Contrary to our first hypothesis, processes were as important for large
      forest-floor bryophytes as for small pocket species. Fire severity, its
      interaction with the quality of available habitat, and its impact on the creation
      of biological legacies played dominant roles in determining community structure.
      In this study, sites with nearly identical forest structure, generated via
      convergent succession after high- and low-severity fire, were compared to see
      whether these sites supported similar bryophyte communities. While similar to
      some degree, both the large forest-floor species and the pocket species differed
      after high-severity fire compared to low-severity fire. This result suggests that
      the "how," or process of habitat generation, influences community composition in
      this system and that a snapshot of habitat conditions taken at only one point in
      time is insufficient to explain species distribution.

PMID- 24279272
TI  - Climate interacts with soil to produce beta diversity in Californian plant
      communities.
AB  - Spatially distinct communities can arise through interactions and feedbacks
      between abiotic and biotic factors. We suggest that, for plants, patches of
      infertile soils such as serpentine may support more distinct communities from
      those in the surrounding non-serpentine matrix in regions where the climate is
      more productive (i.e., warmer and/or wetter). Where both soil fertility and
      climatic productivity are high, communities may be dominated by plants with fast
      growing functional traits, whereas where either soils or climate impose low
      productivity, species with stress-tolerant functional traits may predominate. As
      a result, both species and functional composition may show higher dissimilarity
      between patch and matrix in productive climates. This pattern may be reinforced
      by positive feedbacks, in which higher plant growth under favorable climate and
      soil conditions leads to higher soil fertility, further enhancing plant growth.
      For 96 pairs of sites across a 200-km latitudinal gradient in California, we
      found that the species and functional dissimilarities between communities on
      infertile serpentine and fertile non-serpentine soils were higher in more
      productive (wetter) regions. Woody species had more stress-tolerant functional
      traits on serpentine than non-serpentine soil, and as rainfall increased, woody
      species functional composition changed toward fast-growing traits on non
      serpentine, but not on serpentine soils. Soil organic matter increased with
      rainfall, but only on non-serpentine soils, and the difference in organic matter
      between soils was positively correlated with plant community dissimilarity. These
      results illustrate a novel mechanism wherein climatic productivity is associated
      with higher species, functional, and landscape-level dissimilarity (beta
      diversity).

PMID- 24279273
TI  - Do fungivores trigger the transfer of protective metabolites from host plants to
      arbuscular mycorrhizal hyphae?
AB  - A key objective in ecology is to understand how cooperative strategies evolve and
      are maintained in species networks. Here, we focus on the tri-trophic
      relationship between arbuscular mycorrhizal (AM) fungi, host plants, and
      fungivores to ask if host plants are able to protect their mutualistic
      mycorrhizal partners from being grazed. Specifically, we test whether secondary
      metabolites are transferred from hosts to fungal partners to increase their
      defense against fungivores. We grew Plantago lanceolata hosts with and without
      mycorrhizal inoculum, and in the presence or absence of fungivorous springtails.
      We then measured fungivore effects on host biomass and mycorrhizal abundance
      (using quantitative PCR) in roots and soil. We used high-performance liquid
      chromatography to measure host metabolites in roots, shoots, and hyphae, focusing
      on catalpol, aucubin, and verbascoside. Our most striking result was that the
      metabolite catalpol was consistently found in AM fungal hyphae in host plants
      exposed to fungivores. When fungivores were absent, catalpol was undetectable in
      hyphae. Our results highlight the potential for plant-mediated protection of the
      mycorrhizal hyphal network.

PMID- 24279274
TI  - Regional signatures of plant response to drought and elevated temperature across
      a desert ecosystem.
AB  - The performance of many desert plant species in North America may decline with
      the warmer and drier conditions predicted by climate change models, thereby
      accelerating land degradation and reducing ecosystem productivity. We paired
      repeat measurements of plant canopy cover with climate at multiple sites across
      the Chihuahuan Desert over the last century to determine which plant species and
      functional types may be the most sensitive to climate change. We found that the
      dominant perennial grass, Bouteloua eriopoda, and species richness had nonlinear
      responses to summer precipitation, decreasing more in dry summers than increasing
      with wet summers. Dominant shrub species responded differently to the seasonality
      of precipitation and drought, but winter precipitation best explained changes in
      the cover of woody vegetation in upland grasslands and may contribute to woody
      plant encroachment that is widespread throughout the southwestern United States
      and northern Mexico. Temperature explained additional variability of changes in
      cover of dominant and subdominant plant species. Using a novel empirically based
      approach we identified "climate pivot points" that were indicative of shifts from
      increasing to decreasing plant cover over a range of climatic conditions.
      Reductions in cover of annual and several perennial plant species, in addition to
      declines in species richness below the long-term summer precipitation mean across
      plant communities, indicate a decrease in the productivity for all but the most
      drought-tolerant perennial grasses and shrubs in the Chihuahuan Desert. Overall,
      our regional synthesis of long-term data provides a robust foundation for
      forecasting future shifts in the composition and structure of plant assemblages
      in the largest North American warm desert.

PMID- 24279275
TI  - Bee diversity effects on pollination depend on functional complementarity and
      niche shifts.
AB  - Biodiversity is important for many ecosystem processes. Global declines in
      pollinator diversity and abundance have been recognized, raising concerns about a
      pollination crisis of crops and wild plants. However, experimental evidence for
      effects of pollinator species diversity on plant reproduction is extremely
      scarce. We established communities with 1-5 bee species to test how seed
      production of a plant community is determined by bee diversity. Higher bee
      diversity resulted in higher seed production, but the strongest difference was
      observed for one compared to more than one bee species. Functional
      complementarity among bee species had a far higher explanatory power than bee
      diversity, suggesting that additional bee species only benefit pollination when
      they increase coverage of functional niches. In our experiment, complementarity
      was driven by differences in flower and temperature preferences. Interspecific
      interactions among bee species contributed to realized functional
      complementarity, as bees reduced interspecific overlap by shifting to alternative
      flowers in the presence of other species. This increased the number of plant
      species visited by a bee community and demonstrates a new mechanism for a
      biodiversity-function relationship ("interactive complementarity"). In
      conclusion, our results highlight both the importance of bee functional diversity
      for the reproduction of plant communities and the need to identify
      complementarity traits for accurately predicting pollination services by
      different bee communities.

PMID- 24279276
TI  - Mechanisms underlying plant sexual dimorphism in multi-trophic arthropod
      communities.
AB  - A growing body of research documents the importance of plant genetic effects on
      arthropod community structure. However, the mechanisms underlying these effects
      are often unclear. Additionally, plant genetic effects have largely been
      quantified in common gardens, thus inflating the estimates of their importance by
      minimizing levels of natural variation. Using Valeriana edulis, a dioecious plant
      with genetically based sex determination, we conducted surveys and experiments on
      wild-grown individuals to document field patterns of arthropod association
      between the sexes and the mechanisms underlying these plant genetic effects.
      Three years of surveys revealed strong and consistent sex-biased arthropod
      association in wild-grown plants: female plants supported 4-fold, 1.5-fold, and 4
      fold higher densities of aphids, aphid predators, and aphid-tending ants,
      respectively, compared to males. There was mixed evidence that the female bias
      for aphids was due to higher plant quality, while we found no difference between
      plant sexes in aphid preference or the top-down effects of predators and tending
      ants. Female bias for ants was due to both the greater attractiveness of female
      plants (direct effect mediated by floral nectar) and an independent, weaker
      effect of higher aphid abundance on females (density-mediated indirect effect).
      Conversely, the female bias for predators was driven solely by the greater
      attractiveness of female plants. We did not find interaction modification, i.e.,
      ant-aphid and predator-aphid interactions were equivalent between plant sexes.
      Plant sex explained 0.24%, 2.28%, and 4.42% of the variance in aphids, predators,
      and ants, respectively, values comparable to but slightly weaker than those
      previously reported from common-garden studies. In contrast to the prediction of
      diminished plant genetic effects with increasing trophic level, we show how weak
      indirect effects on predators and parasitoids (via herbivores) can be
      complemented by strong direct effects via common plant traits (floral resources).
      In summary, we document direct and indirect effects of genetically based sex on a
      multi-trophic arthropod community that were expressed in wild-grown plants across
      multiple years.

PMID- 24279277
TI  - Diel horizontal migration in streams: juvenile fish exploit spatial heterogeneity
      in thermal and trophic resources.
AB  - Vertical heterogeneity in the physical characteristics of lakes and oceans is
      ecologically salient and exploited by a wide range of taxa through diel vertical
      migration to enhance their growth and survival. Whether analogous behaviors
      exploit horizontal habitat heterogeneity in streams is largely unknown. We
      investigated fish movement behavior at daily timescales to explore how
      individuals integrated across spatial variation in food abundance and water
      temperature. Juvenile coho salmon made feeding forays into cold habitats with
      abundant food, and then moved long distances (350-1300 m) to warmer habitats that
      accelerated their metabolism and increased their assimilative capacity. This
      behavioral thermoregulation enabled fish to mitigate trade-offs between trophic
      and thermal resources by exploiting thermal heterogeneity. Fish that exploited
      thermal heterogeneity grew at substantially faster rates than did individuals
      that assumed other behaviors. Our results provide empirical support for the
      importance of thermal diversity in lotic systems, and emphasize the importance of
      considering interactions between animal behavior and habitat heterogeneity when
      managing and restoring ecosystems.

PMID- 24279278
TI  - Female elk contacts are neither frequency nor density dependent.
AB  - Identifying drivers of contact rates among individuals is critical to
      understanding disease dynamics and implementing targeted control measures. We
      studied the interaction patterns of 149 female elk (Cervus canadensis)
      distributed across five different regions of western Wyoming over three years,
      defining a contact as an approach within one body length (-2 min). Using
      hierarchical models that account for correlations within individuals, pairs, and
      groups, we found that pairwise contact rates within a group declined by a factor
      of three as group sizes increased 33-fold. Per capita contact rates, however,
      increased with group size according to a power function, such that female elk
      contact rates fell in between the predictions of density- or frequency-dependent
      disease models. We found similar patterns for the duration of contacts. Our
      results suggest that larger elk groups are likely to play a disproportionate role
      in the disease dynamics of directly transmitted infections in elk. Supplemental
      feeding of elk had a limited impact on pairwise interaction rates and durations,
      but per capita rates were more than two times higher on feeding grounds. Our
      statistical approach decomposes the variation in contact rate into individual,
      dyadic, and environmental effects, and provides insight into factors that may be
      targeted by disease control programs. In particular, female elk contact patterns
      were driven more by environmental factors such as group size than by either
      individual or dyad effects.

PMID- 24279279
TI  - Wildlife mortality from infrastructure collisions: statistical modeling of count
      data from carcass surveys.
AB  - Anthropogenic infrastructure is a mortality source for many vertebrate species.
      Mortality is often measured using periodic counts of carcasses or remains at
      infrastructure segments, and bias from carcass removal is estimated via field
      experiments with wildlife carcasses. We describe a model for combining removal
      experiment and carcass count data to estimate underlying process parameters using
      joint likelihood. In the model, the instantaneous number of carcasses present is
      a stochastic birth-death process with Poisson arrivals (carcass addition) and
      proportional deaths (removal of carcasses). The approach accommodates modeling
      heterogeneity in the addition and removal processes using generalized regression.
      Results of fitting the model to a Greater Sage-Grouse (Centrocercus urophasianus)
      fence collision data set show that order of magnitude differences in expected
      carcass counts can be a function of spatial differences in removal and suggest
      caution for interpretation of many published studies. While the model assumption
      of negligible detection error may be tenable for some systems, the modeling
      framework provides a starting point for future state-space versions incorporating
      detection error.

PMID- 24279280
TI  - Using uncertainty estimates in analyses of population time series.
AB  - Recording and monitoring wildlife is crucial for the conservation of wild species
      and the protection of their environment. The most common type of information
      reported from a monitoring scheme is a time series of population abundance
      estimates, but the potential of such data for analyzing population dynamics is
      limited due to lack of information on sampling error. Recent work has shown that
      replicating the sampling process and analyzing replicates jointly in a dynamical
      model can considerably increase estimation efficiency compared to analyzing
      population estimates alone. This method requires that independent replicates are
      available, and model fitting can be complex in general. Often, however,
      population estimates are accompanied by standard errors, or standard errors may
      be estimated from raw data using a sampling model. We evaluate a method where
      standard errors are used in combination with population estimates to account for
      sampling variability in state-space models of population dynamics. The method is
      simple and lends itself readily to data derived from many sampling procedures but
      ignores uncertainty in the standard errors themselves. We simulate data from a
      Gaussian state-space model where several observations, which may come from
      different sites, are available for the population at each time. Fitting the
      simulated data, we show that the method yields similar or even better results
      than a method utilizing all observations, even when there are few observations at
      each time. This holds under a range of simulation settings involving
      heteroscedastic observation error, site effects, and correlation among
      observations. We illustrate the approach on real data from the North American
      Breeding Bird Survey and show that it performs well in comparison to a more
      difficult maximum-likelihood analysis of the full data under non-Gaussian
      sampling error.

PMID- 24279281
TI  - Gelation of vesicles and nanoparticles using water-soluble hydrophobically
      modified chitosan.
AB  - Hydrophobically modified chitosan (hmC) is a self-assembling polymer that has
      attracted recent attention for many applications, including as a hemostatic
      agent. One limitation with chitosan and its derivatives like hmC is that these
      polymers are soluble in water only under acidic conditions (because the pKa of
      chitosan is about 6.5), which could be undesirable for biomedical applications.
      To circumvent this limitation, we have synthesized a derivative of a C12-tailed
      hmC that is soluble in water at neutral pH. This water-soluble hmC (ws-hmC) is
      obtained by grafting O-carboxymethyl groups onto some of the primary hydroxyls on
      hmC. The solubility of ws-hmC at neutral pH is shown to be the result of a net
      anionic character for the polymer due to ionization of the carboxymethyl groups
      (in comparison, hmC is cationic). We also demonstrate that ws-hmC retains the
      self-assembling properties of hmC. Specifically, ws-hmC is able to induce
      gelation at neutral pH in dispersions of anionic surfactant vesicles as well as
      polymethylmethacrylate latex nanoparticles. Gelation is attributed to hydrophobic
      interactions between the hydrophobes on ws-hmC with vesicle bilayers and
      nanoparticle surfaces. In each case, gelation can be reversed by the addition of
      alpha-cyclodextrin, a supramolecule with a hydrophobic cavity that sequesters the
      hydrophobes on the polymer. 

PMID- 24279283
TI  - Use of a versatile high efficiency multiparallel denuder for the sampling of PAHs
      in ambient air: gas and particle phase concentrations, particle size distribution
      and artifact formation.
AB  - The design and performance of a multiparallel plate denuder able to operate at
      low and high-flow (3-30 L/min) for the collection of polycyclic aromatic
      hydrocarbon (PAH) vapor is described. The denuder, in combination with a micro
      orifice uniform deposit impactor (MOUDI) was used to assess processes of artifact
      formation in MOUDIs used with and without an upstream denuder. Duplicate sampling
      trains with an upstream denuder showed good repeatability of the measured gas and
      particle-phase concentrations and low breakthrough in the denuder (3.5-15%). The
      PAH size distributions within undenuded and denuded MOUDIs were studied. Use of
      the denuder altered the measured size distribution of PAHs toward smaller sizes,
      but both denuded and undenuded systems are subject to sampling artifacts. 

PMID- 24279285
TI  - Preparation and characterization of cellulose regenerated from phosphoric acid.
AB  - Native cellulose has a highly crystalline structure stabilized by a strong intra-
      and intermolecular hydrogen-bond network. It is usually not considered as a good
      gelling material and emulsion stabilizer due to its insolubility in water.
      Chemical modification is generally necessary to obtain cellulose derivatives for
      these applications. In this study, we have shown that, by simply disrupting the
      hydrogen-bond network of cellulose with phosphoric acid treatment, the
      regenerated cellulose can be a good gelling material and emulsion stabilizer.
      Microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy
      analysis have confirmed that the regenerated cellulose is primarily amorphous
      with low crystallinity in the structure of cellulose II. Stable aqueous
      suspensions and opaque gels that resist flowing can be obtained with the
      regenerated cellulose at concentrations higher than 0.6% and 1.6%, respectively.
      Moreover, it can effectively stabilize oil-in-water emulsions at concentrations
      less than 1% by a mechanism that combines network and Pickering stabilization. 

PMID- 24279284
TI  - Efficacy of structured education in patients with type 2 diabetes mellitus
      receiving insulin treatment.
AB  - BACKGROUND: The aim of the present study was to assess the efficacy of structured
      education in insulin-treated type 2 diabetes mellitus (T2DM) patients. METHODS:
      In a 16-week open-label randomized controlled study, 1511 T2DM patients with
      inadequate responses to two or more oral antidiabetic drugs (OADs) for >3 months
      (HbA1c >7.5%) were randomized (1:1) to either an education group (structured
      diabetes education plus insulin therapy) or a control group (usual care plus
      insulin therapy). Both groups discontinued previous OADs (except biguanides and
      alpha-glucosidase inhibitors) and started twice daily injections of 30% soluble
      70% isophane recombinant insulin. The primary endpoint was the change in HbA1c
      from baseline. Efficacy and safety data were analyzed for within- and between
      group differences. RESULTS: Of the initial 1511 patients, 1289 completed the
      study (643 in the control group; 646 in the education group). At the end of the
      study, significant reductions in HbA1c versus baseline were evident in both
      groups, but the reduction was greater in the education group (2.16% vs. 2.08%; P
      < 0.05). A higher proportion of patients in the education group achieved target
      HbA1c levels <7% (43.81% vs. 36.86%; P < 0.05) and <=6.5% (28.48% vs. 22.71%; P <
      0.05). In addition, patients in the education group showed greater increments in
      scores and improvement in the Morisky Medication Adherence Scale (P < 0.05). The
      overall incidence of hypoglycemic events was similar in the two groups.
      CONCLUSIONS: Structured education can promote the ability of patients to self
      manage and their compliance with medications, thereby achieving better outcomes.

PMID- 24279287
TI  - Efficacy of antimicrobials extracted from organic pecan shell for inhibiting the
      growth of Listeria spp.
AB  - Growers and processors of USDA certified organic foods are in need of suitable
      organic antimicrobials. The purpose of the research reported here was to develop
      and test natural antimicrobials derived from an all-natural by-product, organic
      pecan shells. Unroasted and roasted organic pecan shells were subjected to
      solvent free extraction to produce antimicrobials that were tested against
      Listeria spp. and L. monocytogenes serotypes to determine the minimum inhibitory
      concentrations (MIC) of antimicrobials. The effectiveness of pecan shell extracts
      were further tested using a poultry skin model system and the growth inhibition
      of the Listeria cells adhered onto the skin model were quantified. The solvent
      free extracts of pecan shells inhibited Listeria strains at MICs as low as 0.38%.
      The antimicrobial effectiveness tests on a poultry skin model exhibited nearly a
      2 log reduction of the inoculated cocktail mix of Listeria strains when extracts
      of pecan shell powder were used. The extracts also produced greater than a 4 log
      reduction of the indigenous spoilage bacteria on the chicken skin. Thus, the
      pecan shell extracts may prove to be very effective alternative antimicrobials
      against food pathogens and supplement the demand for effective natural
      antimicrobials for use in organic meat processing. 

PMID- 24279288
TI  - Heparin promotes the rapid fibrillization of a peptide with low intrinsic
      amyloidogenicity.
AB  - Amyloid deposits in vivo are complex mixtures composed of protein fibrils and
      nonfibrillar components, including polysaccharides of the glycosaminoglycan (GAG)
      class. It has been widely documented that GAGs influence the initiation and
      progress of self-assembly by several disease-associated amyloidogenic proteins
      and peptides in vitro. Here we investigated whether the GAG heparin can serve as
      a cofactor to induce amyloid-like fibril formation in a peptide predicted to have
      a weak propensity to aggregate and not associated with amyloid disorders. We
      selected the 23-residue peptide PLB(1-23), which corresponds to the acetylated
      cytoplasmic domain of the phospholamban transmembrane protein. PLB(1-23) remains
      unfolded in aqueous solution for >24 h and does not bind thioflavin T over this
      time period, in agreement with computer predictions that the peptide has a very
      low intrinsic amyloidogenicity. In the presence of low-molecular mass (5 kDa)
      heparin, which binds PLB(1-23) with micromolar affinity, the peptide undergoes
      spontaneous and rapid assembly into amyloid-like fibrils, the effect being more
      pronounced at pH 5.5 than at pH 7.4. At the lower pH, peptide aggregation is
      accompanied by a transition to a beta-sheet rich structure. These results are
      consistent with the polyanionic heparin serving as a scaffold to enhance
      aggregation by aligning the peptide molecules in the correct orientation and with
      the appropriate periodicity. PLB(1-23) is toxic to cells when added in isolation,
      and promotion of fibril formation by heparin can reduce the toxicity of this
      peptide, consistent with the notion that amyloid-like fibrils represent a benign
      end stage of fibrillization. This work provides insight into the role that
      heparin and other glycosaminoglycans may play in amyloid formation and provides
      therapeutic avenues targeting the reduction of cytotoxicity of species along the
      amyloid formation pathway. 

PMID- 24279289
TI  - Defects are needed for fast photo-induced electron transfer from a nanocrystal to
      a molecule: time-domain ab initio analysis.
AB  - Quantum dot (QD) solar cells constitute an attractive alternative to traditional
      solar cells due to unique electronic and optical properties of QDs. In order to
      achieve high photon-to-electron conversion efficiency, rapid charge separation
      and slow charge recombination are required. We use nonadiabatic molecular
      dynamics combined with time-domain density functional theory to study electron
      transfer from a PbS QD to the rhodamine B (RhB) molecule and subsequent electron
      return from RhB to the QD. The time scale for the electron-hole recombination
      obtained for the system without defects agrees well with the experiment, while
      the simulated time scale for the charge separation is 10-fold longer than the
      experimental value. By performing an atomistic simulation with a sulfur vacancy,
      which is a common defect in PbS systems, we demonstrate that the defect
      accelerates the charge separation. This result is supported further by scaling
      arguments. Missing sulfur creates unsaturated chemical bonds on Pb atoms, which
      form the PbS conduction band. As a result, the QD lowest unoccupied molecular
      orbital (LUMO) is lowered in energy, and the LUMO density extends onto the
      adsorbed molecule, increasing the donor-acceptor interaction. The
      counterintuitive conclusion that defects are essential rather than detrimental to
      functioning of QD solar cells generates an unexpected view on the QD surface
      chemistry. 

PMID- 24279290
TI  - Assessment of health hazard due to natural radioactivity in Kluang District,
      Johor, Malaysia.
AB  - The radiation survey of the ambient environment was conducted using two gamma
      detectors, and the measurement results were used in the computation of the mean
      external radiation dose rate, mean-weighted dose rate and annual effective dose,
      which are 144 nGy h(-1), 0.891 mSv y(-1) and 178 MUSv, respectively. A high
      purity germanium detector was used to determine the activity concentrations of
      (232)Th, (226)Ra and (40)K in soil samples. The results of the gamma spectrometry
      of the soil samples show radioactivity concentration ranges from 19+/-1 to 405+/
      13 Bq kg(-1) with a mean value of 137+/-5 Bq kg(-1) for (232)Th, from 21+/-2 to
      268+/-9 Bq kg(-1)with a mean value of 78+/-3 Bq kg(-1) for (226)Ra and from 23+/
      9 to 1268+/-58 Bq kg(-1) with a mean value of 207+/-13 Bq kg(-1) for (40)K.
      Radium equivalent activity (Raeq) and external hazard index (Hex) were 290 Bq kg(
      1) and 0.784, respectively, which were safe for the population. The mean lifetime
      dose and lifetime cancer risk for each person living in the area with average
      lifetime (70 y) were 12.46 mSv and 7.25*10(-4) Sv year, respectively. The results
      were compared with values given in United Nations Scientific Committee on the
      Effects of Atomic Radiation 2000. 

PMID- 24279291
TI  - Transcription through enhancers suppresses their activity in Drosophila.
AB  - BACKGROUND: Enhancer elements determine the level of target gene transcription in
      a tissue-specific manner, providing for individual patterns of gene expression in
      different cells. Knowledge of the mechanisms controlling enhancer action is
      crucial for understanding global regulation of transcription. In particular,
      enhancers are often localized within transcribed regions of the genome. A number
      of experiments suggest that transcription can have both positive and negative
      effects on regulatory elements. In this study, we performed direct tests for the
      effect of transcription on enhancer activity. RESULTS: Using a transgenic
      reporter system, we investigated the relationship between the presence of pass
      through transcription and the activity of Drosophila enhancers controlling the
      expression of the white and yellow genes. The results show that transcription
      from different promoters affects the activity of enhancers, counteracting their
      ability to activate the target genes. As expected, the presence of a
      transcriptional terminator between the inhibiting promoter and the affected
      enhancer strongly reduces the suppression. Moreover, transcription leads to
      dislodging of the Zeste protein that is responsible for the enhancer-dependent
      regulation of the white gene, suggesting a 'transcription interference' mechanism
      for this regulation. CONCLUSIONS: Our findings suggest a role for pass-through
      transcription in negative regulation of enhancer activity.

PMID- 24279292
TI  - Fumigation of a laboratory-scale HVAC system with hydrogen peroxide for
      decontamination following a biological contamination incident.
AB  - AIMS: To evaluate hydrogen peroxide vapour (H2 O2 ) for its ability to inactivate
      Bacillus spores within a laboratory-scale heating, ventilation and air
      conditioning (HVAC) duct system. METHODS AND RESULTS: Experiments were conducted
      in a closed-loop duct system, constructed of either internally lined or unlined
      galvanized metal. Bacterial spores were aerosol-deposited onto 18-mm-diameter
      test material coupons and strategically placed at several locations within the
      duct environment. Various concentrations of H2 O2 and exposure times were
      evaluated to determine the sporicidal efficacy and minimum exposure needed for
      decontamination. For the unlined duct, high variability was observed in the
      recovery of spores between sample locations, likely due to complex, unpredictable
      flow patterns within the ducts. In comparison, the lined duct exhibited a
      significant desorption of the H2 O2 following the fumigant dwell period and thus
      resulted in complete decontamination at all sampling locations. CONCLUSIONS:
      These findings suggest that decontamination of Bacillus spore-contaminated
      unlined HVAC ducts by hydrogen peroxide fumigation may require more stringent
      conditions (higher concentrations, longer dwell duration) than internally
      insulated ductwork. SIGNIFICANCE AND IMPACT OF THE STUDY: These data may help
      emergency responders when developing remediation plans during building
      decontamination.

PMID- 24279293
TI  - EGFR inhibitors erlotinib and lapatinib ameliorate epidermal blistering in
      pemphigus vulgaris in a non-linear, V-shaped relationship.
AB  - Novel insights into intra-cellular signalling involved in pemphigus vulgaris
      (PV), an autoimmune blistering disease of skin and mucous membranes, are now
      revealing new therapeutic approaches such as the chemical inhibition of PV
      associated signals in conjunction with standard immunosuppressive therapy.
      However, extensive inhibition of signalling molecules that are required for
      normal tissue function and integrity may hamper this approach. Using a neonatal
      PV mouse model, we demonstrate that epidermal blistering can be prevented in a
      dose-dependent manner by clinically approved EGFR inhibitors erlotinib and
      lapatinib, but only up to approximately 50% of normal EGFR activity. At lower
      EGFR activity, blisters again aggravated and were highly exacerbated in mice with
      a conditional deletion of EGFR. Statistical analysis of the relation between EGFR
      activity and the extent of skin blistering revealed the best fit with a non
      linear, V-shaped curve with a median break point at 52% EGFR activity (P =
      0.0005). Moreover, lapatinib (a dual EGFR/ErbB2 inhibitor) but not erlotinib
      significantly reduced blistering in the oral cavity, suggesting that signalling
      mechanisms differ between PV predilection sites. Our results demonstrate that
      future clinical trials evaluating EGFR/ErbB2 inhibitors in PV patients must
      select treatment doses that retain a specific level of signal molecule activity.
      These findings may also be of relevance for cancer patients treated with EGFR
      inhibitors, for whom skin lesions due to extensive EGFR inhibition represent a
      major threat.

PMID- 24279295
TI  - Piscirickettsiosis and Piscirickettsia salmonis in fish: a review.
AB  - The bacterium Piscirickettsia salmonis is the aetiological agent of
      piscirickettsiosis a severe disease that has caused major economic losses in the
      aquaculture industry since its appearance in 1989. Recent reports of P. salmonis
      or P. salmonis-like organisms in new fish hosts and geographical regions have
      increased interest in the bacterium. Because this gram-negative bacterium is
      still poorly understood, many relevant aspects of its life cycle, virulence and
      pathogenesis must be investigated before prophylactic procedures can be properly
      designed. The development of effective control strategies for the disease has
      been limited due to a lack of knowledge about the biology, intracellular growth,
      transmission and virulence of the organism. Piscirickettsiosis has been difficult
      to control; the failure of antibiotic treatment is common, and currently used
      vaccines show variable long-term efficacy. This review summarizes the biology and
      characteristics of the bacterium, including its virulence; the infective strategy
      of P. salmonis for survival and evasion of the host immune response; the host
      immune response to invasion by this pathogen; and newly described features of the
      pathology, pathogenesis, epidemiology and transmission. Current approaches to the
      prevention of and treatment for piscirickettsiosis are discussed. 

PMID- 24279294
TI  - Children, parents and pets exercising together (CPET): exploratory randomised
      controlled trial.
AB  - BACKGROUND: Levels of physical activity (PA) in UK children are much lower than
      recommended and novel approaches to its promotion are needed. The Children,
      Parents and Pets Exercising Together (CPET) study is the first exploratory
      randomised controlled trial (RCT) to develop and evaluate an intervention aimed
      at dog-based PA promotion in families. CPET aimed to assess the feasibility,
      acceptability and potential efficacy of a theory-driven, family-based, dog
      walking intervention for 9-11 year olds. METHODS: Twenty-eight families were
      allocated randomly to either receive a 10-week dog based PA intervention or to a
      control group. Families in the intervention group were motivated and supported to
      increase the frequency, intensity and duration of dog walking using a number of
      behaviour change techniques. Parents in the intervention group were asked to
      complete a short study exit questionnaire. In addition, focus groups with parents
      and children in the intervention group, and with key stakeholders were
      undertaken. The primary outcome measure was 10 week change in total volume of PA
      using the mean accelerometer count per minute (cpm). Intervention and control
      groups were compared using analysis of covariance. Analysis was performed on an
      intention to treat basis. RESULTS: Twenty five families were retained at follow
      up (89%) and 97% of all outcome data were collected at baseline and follow up.
      Thirteen of 14 (93%) intervention group parents available at follow up completed
      the study exit questionnaire and noted that study outcome measures were
      acceptable. There was a mean difference in child total volume of PA of 27 cpm
      (95% CI -70, 123) and -3 cpm (95% CI -60, 54) for intervention and control group
      children, respectively. This was not statistically significant. Approximately 21%
      of dog walking time for parents and 39% of dog walking time for children was
      moderate-vigorous PA. CONCLUSIONS: The acceptability of the CPET intervention and
      outcome measures was high. Using pet dogs as the agent of lifestyle change in PA
      interventions in children and their parents is both feasible and acceptable, but
      did not result in a significant increase in child PA in this exploratory trial.
      TRIAL REGISTRATION: ISRCTN85939423.

PMID- 24279296
TI  - A feasibility study examining the effect on lung cancer diagnosis of offering a
      chest X-ray to higher-risk patients with chest symptoms: protocol for a
      randomized controlled trial.
AB  - BACKGROUND: In order to improve lung cancer survival in the UK, a greater
      proportion of resectable cancers must be diagnosed. It is likely that
      resectability rates would be increased by more timely diagnosis. Aside from
      screening, the only way of achieving this is to reduce the time to diagnosis in
      symptomatic cancers. Currently, lung cancers are mainly diagnosed by general
      practitioners (GPs) using the National Institute for Health and Clinical
      Excellence (NICE) guidelines for urgent referral for chest X-ray, which recommend
      urgent imaging or referral for patients who have one of a number of chest
      symptoms for more than 3 weeks. We are proposing to expand this recommendation to
      include one of a number of chest symptoms of any duration in higher-risk
      patients. METHODS/DESIGN: We intend to conduct a trial of imaging in these higher
      risk patients and compare it with NICE guidelines to see if imaging improves
      stage at diagnosis and resection rates. This trial would have to be large (and
      consequently resource-intensive) because most of these patients will not have
      lung cancer, making optimal design crucial. We are therefore conducting a pilot
      trial that will ascertain the feasibility of running a full trial and provide key
      information that will be required in order to design the full trial. DISCUSSION:
      This trial will assess the feasibility and inform the design of a large, UK-wide,
      clinical trial of a change to the NICE guidelines for urgent referral for chest X
      ray for suspected lung cancer. It utilizes a combination of workshop, health
      economic, quality of life, qualitative, and quantitative methods in order to
      fully assess feasibility. TRIAL REGISTRATION: Clinicaltrials.gov NCT01344005.

PMID- 24279297
TI  - Characterising ChIP-seq binding patterns by model-based peak shape deconvolution.
AB  - BACKGROUND: Chromatin immunoprecipitation combined with massive parallel
      sequencing (ChIP-seq) is widely used to study protein-chromatin interactions or
      chromatin modifications at genome-wide level. Sequence reads that accumulate
      locally at the genome (peaks) reveal loci of selectively modified chromatin or
      specific sites of chromatin-binding factors. Computational approaches (peak
      callers) have been developed to identify the global pattern of these sites, most
      of which assess the deviation from background by applying distribution
      statistics. RESULTS: We have implemented MeDiChISeq, a regression-based approach,
      which--by following a learning process--defines a representative binding pattern
      from the investigated ChIP-seq dataset. Using this model MeDiChISeq identifies
      significant genome-wide patterns of chromatin-bound factors or chromatin
      modification. MeDiChISeq has been validated for various publicly available ChIP
      seq datasets and extensively compared with other peak callers. CONCLUSIONS:
      MeDiChI-Seq has a high resolution when identifying binding events, a high degree
      of peak-assessment reproducibility in biological replicates, a low level of false
      calls and a high true discovery rate when evaluated in the context of gold
      standard benchmark datasets. Importantly, this approach can be applied not only
      to 'sharp' binding patterns--like those retrieved for transcription factors (TFs)
      -but also to the broad binding patterns seen for several histone modifications.
      Notably, we show that at high sequencing depths, MeDiChISeq outperforms other
      algorithms due to its powerful peak shape recognition capacity which facilitates
      discerning significant binding events from spurious background enrichment
      patterns that are enhanced with increased sequencing depths.

PMID- 24279298
TI  - A computationally designed DNA aptamer template with specific binding to
      phosphatidylserine.
AB  - The phospholipid phosphatidylserine (PS) is an early marker exploited for
      detecting apoptosis (PS externalization in the cell membrane bilayer) and one
      factor that is associated with increased amyloid plaque deposition in
      transmissible spongiform encephalopathies (TSEs). PS can therefore be considered
      as a promising target for diagnosis or treatment of diseases. Aptamers (short
      nucleic acid sequences) are a particularly attractive class of materials among
      those currently considered for targeting PS. Here we applied an entropy based
      seed-and-grow strategy to design a DNA aptamer template to bind specifically to
      PS. The binding properties of designed aptamers were investigated computationally
      and experimentally. The studies identify the sequence, 5'-AAAGAC-3', as the
      preferred template for further modifications and studies toward its practical
      implementations.

PMID- 24279299
TI  - Harms to 'others' from alcohol consumption in the minimum unit pricing policy
      debate: a qualitative content analysis of U.K. newspapers (2005-12).
AB  - BACKGROUND AND AIMS: Minimum unit pricing is a fiscal intervention intended to
      tackle the social and health harms from alcohol to individual drinkers and wider
      society. This paper presents the first large-scale qualitative examination of how
      newsprint media framed the debate around the harms of alcohol consumption to
      'others' during the development and passing of minimum unit pricing legislation
      in Scotland. METHODS: Qualitative content analysis was conducted on seven U.K.
      and three Scottish national newspapers between 1 January 2005 and 30 June 2012.
      Relevant articles were identified using the electronic databases Nexis U.K. and
      Newsbank. A total of 403 articles focused on the harms of alcohol consumption to
      'others' and were eligible for detailed coding and analysis. RESULTS: Alcohol
      harms to wider society and communities were identified as being a worsening issue
      increasingly affecting everyone through shared economic costs, social disorder,
      crime and violence. The availability of cheap alcohol was blamed, alongside a
      minority of 'problem' youth binge drinkers. The harm caused to families was less
      widely reported. CONCLUSIONS: If news reporting encourages the public to perceive
      the harms caused by alcohol to wider society as having reached crisis point, a
      population-based intervention may be deemed necessary and acceptable. However,
      the current focus in news reports on youth binge drinkers may be masking the
      wider issue of overconsumption across the broader population.

PMID- 24279300
TI  - Overexpression of OsPIL15, a phytochrome-interacting factor-like protein gene,
      represses etiolated seedling growth in rice.
AB  - Phytochrome-interacting factors (PIFs) regulate an array of developmental
      responses ranging from seed germination to vegetational architecture in
      Arabidopsis. However, information regarding the functions of the PIF family in
      monocots has not been widely reported. Here, we investigate the roles of OsPIL15,
      a member of the rice (Oryza sativa L. cv. Nipponbare) PIF family, in regulating
      seedling growth. OsPIL15 encodes a basic helix-loop-helix factor localized in the
      nucleus. OsPIL15-OX seedlings exhibit an exaggerated shorter aboveground part and
      undeveloped root system relative to wild-type seedlings, suggesting that OsPIL15
      represses seedling growth in the dark. Microarray analysis combined with gene
      ontology analysis revealed that OsPIL15 represses a set of genes involved in
      auxin pathways and cell wall organization or biogenesis. Given the important
      roles of the auxin pathway and cell wall properties in controlling plant growth,
      we speculate that OsPIL15 represses seedling growth likely by regulating the
      auxin pathway and suppressing cell wall organization in etiolated rice seedlings.
      Additionally, exposure to red light or far-red light relieved growth retardation
      and promoted seedling elongation in the OsPIL15-OX lines, despite higher levels
      of OsPIL15 transcripts under red light and far-red light than in the dark. These
      results suggest that light regulation of OsPIL15 expression is probably involved
      in photomorphogenesis in rice. 

PMID- 24279301
TI  - Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case
      report.
AB  - BACKGROUND: Liposarcoma is the most common type of soft tissue sarcoma (STS). It
      is divided into five groups according to histological pattern: well
      differentiated, myxoid, round cell, pleomorphic, and dedifferentiated.
      Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while
      an intraperitoneal location is extremely rare. Only seven cases have been
      reported in literature. Many pathologists recognize that a large number of intra
      abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We
      report a case initially diagnosed as undifferentiated sarcoma that was
      reclassified as intraperitoneal dedifferentiated liposarcoma showing an
      amplification of the MDM2 gene. CASE PRESENTATION: A 59-year-old woman with
      abdominal pain and constipation was referred to the Department of Advanced
      Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November
      2012. On physical examination, a very large firm mass was palpable in the meso
      hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass
      (measuring 10 * 19 cm) that was contiguous with the mesentery and compressed the
      third part of the duodenum and jejunum.At laparotomy, a large mass occupying the
      entire abdomen was found, adhering to the first jejunal loop and involving the
      mesentery. Surgical removal of the tumor along with a jejunal resection was
      performed because the first jejunal loop was firmly attached to the
      tumor.Macroscopic examination showed a solid, whitish, cerebroid, and myxoid
      mass, with variable hemorrhage and cystic degeneration, measuring 26 * 19 * 5 cm.
      Microscopic examination revealed two main different morphologic patterns: areas
      with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case
      was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological
      review showed areas of well-differentiated liposarcoma. Fluorescence in situ
      hybridization (FISH) analysis was performed and demonstrated an amplification of
      the MDM2 gene. Definitive diagnosis was intraperitoneal dedifferentiated
      liposarcoma.No adjuvant therapy was given, but 5 months after laparotomy, the
      patient presented with a locoregional recurrence and chemotherapy with high-dose
      ifosfamide was started. CONCLUSIONS: No guidelines are available for the
      management of intraperitoneal dedifferentiated liposarcoma. We report this case
      to permit the collection of a larger number of cases to improve understanding and
      management of this tumor. Moreover, this study strongly suggests that poorly
      differentiated sarcomas should prompt extensive sampling to demonstrate a well
      differentiated liposarcoma component and, if possible, FISH analysis.

PMID- 24279302
TI  - Focused, high accuracy 5-methylcytosine quantitation with base resolution by
      benchtop next-generation sequencing.
AB  - BACKGROUND: The growing interest in the role of epigenetic modifications in human
      health and disease has led to the development of next-generation sequencing
      methods for whole genome analysis of DNA methylation patterns. However, many
      projects require targeted methylation analysis of specific genes or genomic
      regions. We have developed an approach, termed BiSulfite Amplicon Sequencing
      (BSAS), for hypothesis driven and focused absolute DNA methylation analysis. This
      approach is applicable both to targeted DNA methylation studies as well as to
      confirmation of genome-wide studies. RESULTS: BSAS uses PCR enrichment of
      targeted regions from bisulfite-converted DNA and transposome-mediated library
      construction for rapid generation of sequencing libraries from low (1 ng) sample
      input. Libraries are sequenced using the Illumina MiSeq benchtop sequencer.
      Generating high levels of sequencing depth (<1,000 *) provides for quantitatively
      precise and accurate assessment of DNA methylation levels with base specificity.
      Dual indexing of sequencing libraries allows for simultaneous analysis of up to
      96 samples. We demonstrate the superior quantitative accuracy of this approach as
      compared to existing Sanger sequencing methods. CONCLUSIONS: BSAS can be applied
      to any genomic region from any DNA source, including tissue and cell culture.
      Thus, BSAS provides a new validation approach for rapid and highly quantitative
      absolute CpG methylation analysis of any targeted genomic regions in a high
      throughput manner.

PMID- 24279303
TI  - Predictors of antibiotics co-prescription with antimalarials for patients
      presenting with fever in rural Tanzania.
AB  - BACKGROUND: Successful implementation of malaria treatment policy depends on the
      prescription practices for patients with malaria. This paper describes
      prescription patterns and assesses factors associated with co-prescription of
      antibiotics and artemether-lumefantrine (AL) for patients presenting with fever
      in rural Tanzania. METHOD: From June 2009 to September 2011, a cohort event
      monitoring program was conducted among all patients treated at 8 selected health
      facilities in Ifakara and Rufiji Health and Demographic Surveillance System
      (HDSS). It included all patients presenting with fever and prescribed with AL.
      Logistic regression was used to model the predictors on the outcome variable
      which is co-prescription of AL and antibiotics on a single clinical visit.
      RESULTS: A cohort of 11,648 was recruited and followed up with 92% presenting
      with fever. Presumptive treatment was used in 56% of patients treated with AL. On
      average 2.4 (1 - 7) drugs was prescribed per encounter, indicating co
      prescription of AL with other drugs. Children under five had higher odds of AL
      and antibiotics co-prescription (OR = 0.63, 95% CI: 0.46 - 0.85) than those aged
      more than five years. Patients testing negative had higher odds (OR = 2.22, 95%
      CI: 1.65 - 2.97) of AL and antibiotics co-prescription. Patients receiving
      treatment from dispensaries had higher odds (OR = 1.45, 95% CI: 0.84 - 2.30) of
      AL and antibiotics co-prescription than those served in health centres even
      though the deference was not statistically significant. CONCLUSION: Regardless
      the fact that Malaria is declining but due to lack of laboratories and mRDT in
      most health facilities in the rural areas, clinicians are still treating malaria
      presumptively. This leads them to prescribe more drugs to treat all
      possibilities.

PMID- 24279304
TI  - SNP genotyping reveals genetic diversity between cultivated landraces and
      contemporary varieties of tomato.
AB  - BACKGROUND: The tomato (Solanum lycopersium L.) is the most widely grown
      vegetable in the world. It was domesticated in Latin America and Italy and Spain
      are considered secondary centers of diversification. This food crop has
      experienced severe genetic bottlenecks and modern breeding activities have been
      characterized by trait introgression from wild species and divergence in
      different market classes. RESULTS: With the aim to examine patterns of
      polymorphism, characterize population structure and identify putative loci under
      positive selection, we genotyped 214 tomato accessions (which include cultivated
      landraces, commercial varieties and wild relatives) using a custom-made Illumina
      SNP-panel. Most of the 175 successfully scored SNP loci were found to be
      polymorphic. Population structure analysis and estimates of genetic
      differentiation indicated that landraces constitute distinct sub-populations.
      Furthermore, contemporary varieties could be separated in groups (processing,
      fresh and cherry) that are consistent with the recent breeding aimed at market
      class specialization. In addition, at the 95% confidence level, we identified 30,
      34 and 37 loci under positive selection between landraces and each of the groups
      of commercial variety (cherry, processing and fresh market, respectively). Their
      number and genomic locations imply the presence of some extended regions with
      high genetic variation between landraces and contemporary varieties. CONCLUSIONS:
      Our work provides knowledge concerning the level and distribution of genetic
      variation within cultivated tomato landraces and increases our understanding of
      the genetic subdivision of contemporary varieties. The data indicate that
      adaptation and selection have led to a genomic signature in cultivated landraces
      and that the subpopulation structure of contemporary varieties is shaped by
      directed breeding and largely of recent origin. The genomic characterization
      presented here is an essential step towards a future exploitation of the
      available tomato genetic resources in research and breeding programs.

PMID- 24279305
TI  - Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study
      protocol for a double-blind randomized placebo-controlled trial.
AB  - BACKGROUND: Schizophrenia is understood to be a heterogeneous brain condition
      with overlapping symptom dimensions. The negative symptom dimension, with its
      protean cognitive manifestations, responds poorly to treatment, which can be a
      particular challenge in countries where clozapine therapy is not available.
      Preliminary data indicate that minocycline may be beneficial adjunct in the
      treatment of schizophrenia: positive, negative, and cognitive symptoms.In this
      study we aim to assess the efficacy of adjunctive minocycline to alleviate
      symptoms of schizophrenia in patients who have failed to respond to a therapeutic
      trial of antipsychotic medications. METHODS: The study is a parallel group,
      double-blind, randomized, placebo-controlled trial. Participants will be adults
      (aged 18 years and above) with first episode or relapse episode of schizophrenia
      of under 5 years' duration. Patients who failed to show adequate therapeutic
      response to at least one antipsychotic medication given for a minimum of 4 weeks
      will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry
      clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will
      be required to detect a five-point mean difference between the intervention arms
      adjusting for baseline symptom severity, at 90% power and 95% confidence.
      Patients in the intervention arm will receive minocycline (200 mg/day orally)
      added on to the regular antipsychotic medications participants are already on.
      Those in the placebo arm will receive an inactive compound identical in physical
      appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis
      will be established using the operational criteria for research (OPCRIT). Primary
      outcome measure will be a change in symptom severity measured using the positive
      and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome
      measures will include changes in severity of negative symptoms, proportion
      achieving remission, and level of functioning. Whether changes are maintained
      post intervention will also be measured (PANSS). Key assessment for the primary
      outcome will be conducted at the end of trial (week 12). One post-intervention
      assessment will be conducted 4 weeks after the end of intervention (week 16) to
      determine sustainability of change. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier: NCT01809158.

PMID- 24279307
TI  - Gene dysregulation by histone variant H2A.Z in bladder cancer.
AB  - BACKGROUND: The incorporation of histone variants into nucleosomes is one of the
      main strategies that the cell uses to regulate the structure and function of
      chromatin. Histone H2A.Z is an evolutionarily conserved histone H2A variant that
      is preferentially localized within nucleosomes at the transcriptional start site
      (TSS). H2A.Z reorganizes the local chromatin structure and recruits the
      transcriptional machinery for gene activation. High expression of H2A.Z has been
      reported in several types of cancers and is causally linked to genomic
      instability and tumorigenesis. However, it is not entirely clear how H2A.Z
      overexpression in cancer cells establishes aberrant chromatin states and promotes
      gene expression. RESULTS: Through integration of genome-wide H2A.Z ChIP-seq data
      with microarray data, we demonstrate that H2A.Z is enriched around the TSS of
      cell cycle regulatory genes in bladder cancer cells, and this enrichment is
      correlated with the elevated expression of cancer-promoting genes. RNAi-mediated
      knockdown of H2A.Z in the cancer cells causes transcriptional suppression of
      multiple cell cycle regulatory genes with a distinct decrease in cell
      proliferation. H2A.Z nucleosomes around the TSS have higher levels of
      H3K4me2/me3, which coincides with the recruitment of two chromatin factors, WDR5
      and BPTF. The observed recruitment is functional, as the active states of H2A.Z
      target genes are largely erased by suppressing the expression of WDR5 or BPTF,
      effects resembling H2A.Z knockdown. CONCLUSIONS: We conclude that H2A.Z is
      overexpressed in bladder cancer cells and contributes to cancer-related
      transcription pathways. We also provide evidence in support of the engagement of
      H3K4me2/me3 and WDR5/BPTF in H2A.Z-induced cancer pathogenesis. Further studies
      are warranted to understand how H2A.Z overexpression contributes to the
      recruitment of the full repertoire of transcription machinery to target genes in
      bladder cancer cells.

PMID- 24279306
TI  - RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective
      oocyte/embryo competence and potentially reliable predictors of embryo
      developmental competence in PCOS patients.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic
      disorder in women. The developmental competence of oocytes and embryos in PCOS
      patients is reduced to a certain extent (comparing to non-PCOS patients, the high
      quality embryo rate was decreased by 16% from the data of our centre) during the
      in vitro fertilization (IVF) process. Cross-talk between the oocyte and cumulus
      cells is critical for oocyte maturation and embryo competence. In this study, we
      have evaluated the transcription of specific genes in cumulus cells harvested
      from pre-ovulatory follicles of PCOS patients before IVF, according to individual
      oocyte nuclear maturity and developmental competence. Seven genes (RUNX2, PSAT1,
      ADAMTS9, CXCL1, CXCL2, CXCL3, and ITGB5) were targeted from our previous cDNA
      microarray data which isolated genes related to oocyte nuclear maturation in PCOS
      patients. Two additional genes which had been found to be associated with oocyte
      maturation or embryo quality in non-PCOS patients (GPX3 and PTX3) were also
      studied. METHODS: The mRNA expression levels of cumulus cells were detected by
      qRT- PCR. RESULTS: Consistent with our previous cDNA microarray data, with the
      exception of GPX3 and PTX3, the selected 7 genes were related to oocyte nuclear
      maturation in PCOS patients. Noticeably, the expression level of RUNX2 was lower
      in cumulus cells derived from oocytes that could develop into blastocysts than
      the level of expression from oocytes that could not. The PTX3 expression level
      was significantly lower in cumulus cells from oocytes with two normal pronuclei
      than that from oocytes that formed >2 pronuclei (MPN) after fertilization. GPX3
      mRNA levels were decreased in cumulus cells isolated from oocytes that developed
      into blastocysts with high potential development competence. CONCLUSIONS: Several
      cumulus cell genes were associated with oocyte maturation, fertilization and
      embryo quality in PCOS patients. RUNX2 and GPX3 are candidate genetic markers in
      the monitoring of embryo quality for PCOS patients, whereas PTX3 mainly played a
      role in fertilization process. Together with morphological evaluation, cumulus
      cells genes may serve as biomarkers of oocyte and embryo selection during the IVF
      process for PCOS patients and may advance our understanding of PCOS.

PMID- 24279308
TI  - Efficacy, safety and tolerability of tofacitinib in patients with an inadequate
      response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized
      double-blind controlled studies.
AB  - BACKGROUND: This meta-analysis was conducted to determine the efficacy, safety
      and tolerability of tofacitinib in the treatment of rheumatoid arthritis in
      patients with an inadequate response or intolerance to at least one of the
      nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS:
      Electronic based literature search was conducted in the databases of HINARI
      (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane
      library. The studies included in the meta-analysis were double-blind randomized
      clinical trials that were conducted in treatment-refractory or intolerant
      patients with rheumatoid arthritis. The odds ratios (OR), standardized mean
      differences (SMD) and the 95% confidence intervals (95% CI) were determined by
      using the random effects model. Heterogeneity among the included studies was
      evaluated by I2 statistics. RESULTS: The odds of tofacitinib treated patients who
      met the criteria for an at least a 20% improvement in the American College of
      Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated
      patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the
      discontinuation rate due to adverse events was not different from placebo groups,
      tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to
      2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to 
      0.223) and elevated levels of LDL cholesterol and liver enzymes. CONCLUSIONS:
      Tofacitinib was effective in the treatment of active rheumatoid arthritis in
      patients with an inadequate response or intolerance to at least one DMARDs.
      However, treatment with tofacitinib was associated with infections and laboratory
      abnormalities.

PMID- 24279310
TI  - Age-period cohort analysis of AIDS incidence rates in Rio de Janeiro, Brazil,
      1985-2009.
AB  - INTRODUCTION: The long average incubation time from HIV infection to AIDS makes
      it difficult to estimate the recent tendencies of HIV from AIDS incidence data.
      The objective of this study was to investigate the effects of three temporal
      components in AIDS incidence in the state of Rio de Janeiro, Brazil - age,
      period, and cohort. METHODS: Age-specific AIDS incidence rates per 100,000 from
      Rio de Janeiro (Brazil) were calculated for both sexes using five-year age
      classes from 1985 to 2009 based on reported data from the Notifiable Disease
      Information System of the Brazilian Ministry of Health and from census population
      counts. Multivariate negative binomial models were used to analyze the risk of
      AIDS by age, period, and birth cohort. RESULTS: From 1985 to 2009, AIDS incidence
      initially increased with age in each birth cohort and then decreased (except for
      individuals born from 1971-1979 to 1986-1994). High peaks in the rates in each
      birth cohort were detected in 1995-1999 for males and in 2000-2004 for females.
      Multivariate analysis showed the maximum risk of AIDS in the 30-34 age group and
      1958-1962 birth cohort. CONCLUSION: Age, birth cohort, and period effects all may
      have influenced the AIDS incidence rates over the period investigated. From 1985
      to 1999, comparison of the tendencies (by age) of the period with the birth
      cohort revealed opposing tendencies in individuals older than 29 years and in the
      youngest age groups (0 to 14 years). From 2000 to 2009, a strong age effect can
      be observed in both sexes. Consistent changes in period tendency curves suggest
      the occurrence of period effects. A reduction in the intensity of the risk of
      AIDS can be observed after 2000-2004.

PMID- 24279309
TI  - De novo transcriptome sequencing of radish (Raphanus sativus L.) and analysis of
      major genes involved in glucosinolate metabolism.
AB  - BACKGROUND: Radish (Raphanus sativus L.), is an important root vegetable crop
      worldwide. Glucosinolates in the fleshy taproot significantly affect the flavor
      and nutritional quality of radish. However, little is known about the molecular
      mechanisms underlying glucosinolate metabolism in radish taproots. The limited
      availability of radish genomic information has greatly hindered functional
      genomic analysis and molecular breeding in radish. RESULTS: In this study, a high
      throughput, large-scale RNA sequencing technology was employed to characterize
      the de novo transcriptome of radish roots at different stages of development.
      Approximately 66.11 million paired-end reads representing 73,084 unigenes with a
      N50 length of 1,095 bp, and a total length of 55.73 Mb were obtained. Comparison
      with the publicly available protein database indicates that a total of 67,305
      (about 92.09% of the assembled unigenes) unigenes exhibit similarity (e -value <=
      1.0e-5) to known proteins. The functional annotation and classification including
      Gene Ontology (GO), Clusters of Orthologous Group (COG) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) analysis revealed that the main activated genes in
      radish taproots are predominantly involved in basic physiological and metabolic
      processes, biosynthesis of secondary metabolite pathways, signal transduction
      mechanisms and other cellular components and molecular function related terms.
      The majority of the genes encoding enzymes involved in glucosinolate (GS)
      metabolism and regulation pathways were identified in the unigene dataset by
      targeted searches of their annotations. A number of candidate radish genes in the
      glucosinolate metabolism related pathways were also discovered, from which, eight
      genes were validated by T-A cloning and sequencing while four were validated by
      quantitative RT-PCR expression profiling. CONCLUSIONS: The ensuing transcriptome
      dataset provides a comprehensive sequence resource for molecular genetics
      research in radish. It will serve as an important public information platform to
      further understanding of the molecular mechanisms involved in biosynthesis and
      metabolism of the related nutritional and flavor components during taproot
      formation in radish.

PMID- 24279311
TI  - Knowledge, use and management of native wild edible plants from a seasonal dry
      forest (NE, Brazil).
AB  - BACKGROUND: Despite being an ancient practice that satisfies basic human needs,
      the use of wild edible plants tends to be forgotten along with associated
      knowledge in rural communities. The objective of this work is to analyze existing
      relationships between knowledge, use, and management of native wild edible plants
      and socioeconomic factors such as age, gender, family income, individual income,
      past occupation and current occupation. METHODS: The field work took place
      between 2009 and 2010 in the community of Carao, Altinho municipality, in the
      state of Pernambuco in northeastern Brazil. We conducted semi-structured
      interviews with 39 members of the community regarding knowledge, use and
      management of 14 native wild edible plants from the Caatinga region,
      corresponding to 12 vegetable species. In parallel, we documented the
      socioeconomic aspects of the interviewed population (age, gender, family income,
      individual income, past occupation and current occupation). RESULTS: Knowledge
      about edible plants was related to age but not to current occupation or use.
      Current use was not associated with age, gender or occupation. The association
      between age and past use may indicate abandonment of these resources. CONCLUSION:
      Because conservation of the species is not endangered by their use but by
      deforestation of the ecosystems in which these plants grow, we suggest that the
      promotion and consumption of the plants by community members is convenient and
      thereby stimulates the appropriation and consequent protection of the ecosystem.
      To promote consumption of these plants, it is important to begin by teaching
      people about plant species that can be used for their alimentation, disproving
      existing myths about plant use, and encouraging diversification of use by
      motivating the invention of new preparation methods. An example of how this can
      be achieved is through events like the "Preserves Festival".

PMID- 24279312
TI  - Predictors of breastfeeding exclusivity in three cities of China.

PMID- 24279314
TI  - Measures and procedures utilized to determine the added value of microprocessor
      controlled prosthetic knee joints: a systematic review.
AB  - BACKGROUND: The effectiveness of microprocessor-controlled prosthetic knee joints
      (MPKs) has been assessed using a variety of outcome measures in a variety of
      health and health-related domains. However, if the patient is to receive a
      prosthetic knee joint that enables him to function optimally in daily life, it is
      vital that the clinician has adequate information about the effects of that
      particular component on all aspects of persons' functioning. Especially
      information concerning activities and participation is of high importance, as
      this component of functioning closely describes the person's ability to function
      with the prosthesis in daily life. The present study aimed to review the outcome
      measures that have been utilized to assess the effects of microprocessor
      controlled prosthetic knee joints (MPK), in comparison with mechanically
      controlled prosthetic knee joints, and aimed to classify these measures according
      to the components and categories of functioning defined by the International
      Classification of Functioning, Disability and Health (ICF). Subsequently, the
      gaps in the scientific evidence regarding the effectiveness of MPKs were
      determined. METHODS: A systematic literature search in 6 databases (i.e. PubMed,
      CINAHL, Cochrane Library, Embase, Medline and PsychInfo) identified scientific
      studies that compared the effects of using MPKs with mechanically controlled
      prosthetic knee joints on persons' functioning. The outcome measures that have
      been utilized in those studies were extracted and categorized according to the
      ICF framework. Also, a descriptive analysis regarding all studies has been
      performed. RESULTS: A total of 37 studies and 72 outcome measures have been
      identified. The majority (67%) of the outcome measures that described the effects
      of using an MPK on persons' actual performance with the prosthesis covered the
      ICF body functions component. Only 31% of the measures on persons' actual
      performance investigated how an MPK may affect performance in daily life.
      Research also typically focused on young, fit and active persons. CONCLUSIONS:
      Scientifically valid evidence regarding the performance of persons with an MPK in
      everyday life is limited. Future research should specifically focus on activities
      and participation to increase the understanding of the possible functional added
      value of MPKs.

PMID- 24279313
TI  - Adenovirus vectors for gene therapy, vaccination and cancer gene therapy.
AB  - Adenovirus vectors are the most commonly employed vector for cancer gene therapy.
      They are also used for gene therapy and as vaccines to express foreign antigens.
      Adenovirus vectors can be replication-defective; certain essential viral genes
      are deleted and replaced by a cassette that expresses a foreign therapeutic gene.
      Such vectors are used for gene therapy, as vaccines, and for cancer therapy.
      Replication-competent (oncolytic) vectors are employed for cancer gene therapy.
      Oncolytic vectors are engineered to replicate preferentially in cancer cells and
      to destroy cancer cells through the natural process of lytic virus replication.
      Many clinical trials indicate that replication-defective and replication
      competent adenovirus vectors are safe and have therapeutic activity. 

PMID- 24279315
TI  - High-frequency rTMS on DLPFC increases prosocial attitude in case of decision to
      support people.
AB  - Engaging in prosocial behavior was explored in the present research, by
      investigating the role of dorsolateral prefrontal cortex (DLPFC) in modulation of
      intention to support other people and of emotional attuning as it was expressed
      by facial feedback (electromiography, EMG). High-frequency rTMS was applied on
      DLPFC to 25 subjects when they were required to choose to directly intervene or
      not to support other people in emotionally valenced social situations
      (cooperative, noncooperative, conflictual, neutral contexts). Two control
      conditions were included in the experimental design to control the simple
      stimulation effect (sham condition with absence of TMS stimulation) and the
      location effect (control site condition with Pz stimulation). In comparison with
      sham and control condition, rTMS stimulation induced increased prosocial behavior
      in all the emotional situations. Moreover, as a function of valence, zygomatic
      (for positive situations) and corrugators (for negative situations) muscle
      activity was increased, with significant effect by DLPFC stimulation which
      induced a "facilitation effect". In addition, negative situations showed a higher
      rTMS impact for both behavioral and EMG responsiveness. Finally, prosocial
      behavior was found to be predicted (regression analysis) by EMG variations, as a
      function of the negative versus positive valence. The prefrontal circuit was
      suggested to support emotional responsiveness and facial feedback in order to
      facilitate the prosocial behavior.

PMID- 24279316
TI  - In vivo multimodality imaging and cancer therapy by near-infrared light-triggered
      trans-platinum pro-drug-conjugated upconverison nanoparticles.
AB  - Controlling anticancer drug activity and release on demand is very significant in
      cancer therapy. The photoactivated platinum(IV) pro-drug is stable in the dark
      and can be activated by UV light. In this study, we develop a multifunctional
      drug delivery system combining upconversion luminescence/magnetic
      resonance/computer tomography trimodality imaging and NIR-activated platinum pro
      drug delivery. We use the core-shell structured upconversion nanoparticles to
      convert the absorbed NIR light into UV to activate the trans-platinum(IV) pro
      drug, trans,trans,trans-[Pt(N3)2(NH3)(py)(O2CCH2CH2COOH)2]. Compared with using
      the UV directly, the NIR has a higher tissue penetration depth and is less
      harmful to health. Meanwhile, the upconversion nanoparticles can effectively
      deliver the platinum(IV) pro-drugs into the cells by endocytosis. The mice
      treated with pro-drug-conjugated nanoparticles under near-infrared (NIR)
      irradiation demonstrated better inhibition of tumor growth than that under direct
      UV irradiation. This multifunctional nanocomposite could be used as multimodality
      bioimaging contrast agents and transducers by converting NIR light into UV for
      control of drug activity in practical cancer therapy. 

PMID- 24279317
TI  - One-step microfluidic synthesis of Janus microhydrogels with anisotropic thermo
      responsive behavior and organophilic/hydrophilic loading capability.
AB  - We report one-step microfluidic synthesis and characterization of novel Janus
      microhydrogels composed entirely of the same base material, N-isopropylacrylamide
      (NIPAAm). The microhydrogels were fabricated by the microfluidic generation of
      Janus monomer microdroplets based on separation of a supersaturated aqueous
      NIPAAm solution into NIPAAm-rich and -poor phases followed by UV irradiation. The
      resulting Janus microhydrogels exhibited tunable anisotropic thermo-responsive
      behavior and organophilic/hydrophilic loading capability. 

PMID- 24279318
TI  - Comparison of the essential oil content and composition of the spathe, buds and
      pollen of Phoenix dactylifera.
AB  - Several medicinal applications have been reported for different components of
      date palm. The inflorescence of the male date tree is composed of spathe that
      surrounds many buds containing pollen. In this study, a comparison between the
      content and composition of the essential oils obtained from these three
      components of an inflorescence was made. After obtaining each oil using hydro
      distillation method, the oil yield was measured as the weight ratio of the oil to
      the distilled sample (w/w %) and the chemical composition of the oil was
      determined by gas chromatography-mass spectrometry analysis. It was observed that
      the pollen possessed the most oil content (1.47%) composed of 68.04% oleic acid,
      whereas the content of this fatty acid in the spathe and bud oils was found to be
      less than 0.05% and 5.65%, respectively. Spathe oil was dominated by 3,4
      dimethoxytoluene (52.90%) while the main constituent of the bud oil was trans
      caryophyllene (44.20%). 

PMID- 24279320
TI  - Does routine clinical practice reproduce the outcome of large prospective trials?
      The analysis of institutional database on patients with limited-disease small
      cell lung cancer.
AB  - We performed the analysis of database on 409 patients with LD-SCLC to evaluate as
      to what extent the clinical outcome of large prospective trials was reproduced in
      routine practice. The analysis has shown that the hazard rate of death in the
      absence of prophylactic cranial irradiation (PCI) adjusted for the effects of
      confounding factors, appeared larger than that reported in the trials on PCI in
      LD-SCLC, and was comparable to that estimated for extensive disease. Less intense
      routine staging procedures, compared to the trial settings, contributed for such
      outcome. Hyperfractionated thoracic radiotherapy provided survival advantage
      similar to that reported in the literature. 

PMID- 24279319
TI  - Ligands for glaucoma-associated myocilin discovered by a generic binding assay.
AB  - Mutations in the olfactomedin domain of myocilin (myoc-OLF) are the strongest
      link to inherited primary open angle glaucoma. In this recently identified
      protein misfolding disorder, aggregation-prone disease variants of myocilin
      hasten glaucoma-associated elevation of intraocular pressure, leading to vision
      loss. Despite its well-documented pathogenic role, myocilin remains a domain of
      unknown structure or function. Here we report the first small-molecule ligands
      that bind to the native state of myoc-OLF. To discover these molecules, we
      designed a general label-free, mix-and-measure, high throughput chemical assay
      for restabilization (CARS), which is likely readily adaptable to discover ligands
      for other proteins. Of the 14 hit molecules identified from screening myoc-OLF
      against the Sigma-Aldrich Library of Pharmacologically Active Compounds using
      CARS, surface plasmon resonance binding studies reveal three are stoichiometric
      ligand scaffolds with low micromolar affinity. Two compounds, GW5074 and
      apigenin, inhibit myoc-OLF amyloid formation in vitro. Structure-activity
      relationship-based soluble derivatives reduce aggregation in vitro as well as
      enhance secretion of full-length mutant myocilin in a cell culture model. Our
      compounds set the stage for a new chemical probe approach to clarify the
      biological function of wild-type myocilin and represent lead therapeutic
      compounds for diminishing intracellular sequestration of toxic mutant myocilin. 

PMID- 24279321
TI  - Characterizations of structural, biochemical, and nutritive profiles in silage
      among cool-season corn cultivars in relation to heat units (aCHU, dCHU) with
      curvilinear response and multivariate analyses.
AB  - Molecular spectroscopy is able to reveal structural features of biomaterials.
      Corn grown in Canadian prairies is known as cool-season corn, which is different
      from warm-season corn varieties. To our knowledge, to date, there has been no
      study on the magnitude difference in structure on a molecular basis among
      cultivars, no study on biochemical and nutritive profiles associated with heat
      unit, and no study on how heat unit affects the molecular structure and
      biochemical and nutritive profiles. This study investigates how corn varieties
      grown in cooler climates are affected by crop heat units (CHU) in relation to
      molecular spectral profiles, nutrient storage, biochemical composition, and
      nutritive value of silage among different cool-season corn cultivars. Corn
      cultivars (Pioneer and Dekalb) were from seven farm locations, and samples were
      analyzed for major nutrients (digestible and metabolic energy and protein). The
      Fourier transform infrared (FT/IR) spectroscopic technique was applied to
      understand and differentiate molecular structural spectral profiles in silage. A
      correlation (P < 0.05) of CHU with some nutrients (mean +/- SD, %DM) (CP, 8.1 +/-
      1.3, r = 0.56; NDF, 56.3 +/- 3.5, r = -0.54; ADF, 33.6 +/- 2.3, r = -0.71; NDICP,
      1.6 +/- 0.4, r = -0.66; SCP, 4.2 +/- 1.3, r = 0.61), protein and carbohydrate
      fractions (mean +/- SD, %DM) (PB1 (= fast degradable protein fraction), 1.3 +/-
      0.4, r = 0.54; PB3 (= slowly degradable protein fraction), 1.5 +/- 0.4, r = 
      0.74; CB2 (= medium degradable carbohydrate fraction), 45.1 +/- 2.8, r = -0.65;
      CB3 (= slowly degradable carbohydrate fraction), 13.9 +/- 0.9, r = -0.54) and
      intestinal availability of ruminally degraded fractions (mean +/- SD, %DM)
      (rdPB1, 1.1 +/- 0.3, r = 0.54; rdPB3, 1.0 +/- 0.3, r = -0.74; RDP, 6.6 +/- 1.2, r
      = 0.59; rdCB2, 40.0 +/- 2.5, r = -0.65; rdCB3, 8.9 +/- 0.6, r = 0.54; RDCHO, 50.1
      +/- 2.9, r = -0.65) was found contentious. Molecular spectral data indicated many
      similarities and few differences among the cultivars. However, CHU correlated (r
      = -0.4, P < 0.05) with molecular spectral intensity ratio of carbohydrate to
      amide I. This result indicates that molecular structural differences may be
      influenced by epiphytic bacterial compounds. Cool corn cultivars were grown
      acceptably well in cooler dry climates, and those silages had acceptable nutrient
      levels for cattle. Cultivars that reached target CHU were found to be optimal in
      nutrient and energy synchronization aspect. 

PMID- 24279322
TI  - Characterization of two quinone radicals in the NADH:ubiquinone oxidoreductase
      from Escherichia coli by a combined fluorescence spectroscopic and
      electrochemical approach.
AB  - The NADH:ubiquinone oxidoreductase (complex I) couples the transfer of electrons
      from NADH to ubiquinone with the translocation of protons across the membrane. It
      was proposed that the electron transfer involves quinoid groups localized at the
      end of the electron transfer chain. To identify these groups, fluorescence
      excitation and emission spectra of Escherichia coli complex I and its fragments,
      namely, the NADH dehydrogenase fragment containing the flavin mononucleotide and
      six iron-sulfur (Fe-S) clusters, and the quinone reductase fragment containing
      three Fe-S clusters were measured. Signals sensitive to reduction by either NADH
      or dithionite were detected within the complex and the quinone reductase fragment
      and attributed to the redox transition of protonated ubiquinone radicals. A
      fluorescence spectroscopic electrochemical redox titration revealed midpoint
      potentials of -37 and- 235 mV (vs the standard hydrogen electrode) for the redox
      transitions of the quinone radicals in complex I at pH 6 with an absorption
      around 325 nm and a fluorescence emission at 460/475 nm. The role of these
      cofactor(s) for electron transfer is discussed. 

PMID- 24279324
TI  - Formal synthesis of (+/-)-cycloclavine.
AB  - An efficient formal synthesis of (+/-)-cycloclavine is achieved in seven steps
      and 27% overall yield from the known 2-(4-bromo-1-tosyl-1H-indol-3
      yl)acetaldehyde. Key features include an iron(III)-catalyzed aza-Cope-Mannich
      cyclization and an intramolecular Heck reaction or a self-terminating 6-exo-trig
      aryl radical-alkene cyclization. 

PMID- 24279326
TI  - Establishment of ruminal bacterial community in dairy calves from birth to
      weaning is sequential.
AB  - AIM: Establishment of ruminal bacterial community in dairy calves. METHODS AND
      RESULTS: Rumen bacterial community was analysed on 6 calves bred according to
      commercial practices from day one to weaning at day 83 of age, using 454 16S rRNA
      based pyrosequencing. Samples taken at day 1 did not produce amplicons. Analysis
      of data revealed a three-stage implantation process with a progressive but
      important shift of composition. At day 2, the bacterial community was mainly
      composed of Proteobacteria (70%) and Bacteroidetes (14%), and Pasteurellaceae was
      the dominant family (58%). The bacterial community abruptly changed between days
      2 and 3, and until day 12, dominant genera were Bacteroides (21%), Prevotella
      (11%), Fusobacterium (5%) and Streptococcus (4%). From 15 to 83 days, when solid
      food intake rapidly increased, Prevotella became dominant (42%) and many genera
      strongly decreased or were no longer detected. A limited number of bacteria
      genera correlated with feed intake, rumen volatile fatty acids and enzymatic
      activities. CONCLUSION: The ruminal bacterial community is established before
      intake of solid food, but solid food arrival in turn shapes this community.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insight into the
      establishment of calves' rumen bacterial community and suggests a strong effect
      of diet.

PMID- 24279327
TI  - The association of childhood physical abuse with the onset and extent of drug use
      among regular injecting drug users.
AB  - AIMS: To determine whether childhood physical abuse (CPA) histories were
      associated with age of onset of psychoactive substance use and injecting, and the
      extent of polydrug use among injecting drug users (IDU). DESIGN: Cross-sectional.
      SETTING: Sydney, Australia. PARTICIPANTS AND MEASUREMENTS: A total of 300 IDU
      were administered a structured interview examining the prevalence and severity of
      CPA and drug use histories. FINDINGS: Of the participants, 40.3% had experienced
      severe abuse (SA), 34.0% mild-moderate abuse (MMA) and 25.7% no abuse history
      (NA). After controlling for other variables, a history of severe CPA was a
      significant independent correlate of an earlier age at first alcohol intoxication
      compared to both the NA (beta = -0.23, P < 0.01) and MMA (beta = 0.20, P < 0.01)
      groups. Severe CPA was also a significant independent correlate of an earlier age
      at first illicit drug use compared to both the NA (beta = -0.16, P < 0.05) and
      MMA (beta = -0.15, P < 0.05) groups. In contrast, CPA histories were not
      independently associated with the onset of injecting drug use. After controlling
      for potential confounders, both the MMA (beta = 0.28, P < 0.001) and SA (beta =
      0.27, P < 0.001) groups were associated with more extensive life-time polydrug
      use, but did not differ from each other (P = 0.82). After controlling for
      potential confounders, both MMA (beta = 0.20, P < 0.01) and SA (beta = 0.33, P <
      0.001) group membership were associated with more extensive recent polydrug use
      but, again, did not differ significantly from each other (P = 0.08). CONCLUSIONS:
      Severe childhood physical abuse severity is associated with an earlier initiation
      into drug use. Any level of abuse is associated with more extensive life-time and
      recent polydrug use.

PMID- 24279325
TI  - Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1.
AB  - BACKGROUND: Hansenula polymorpha DL1 is a methylotrophic yeast, widely used in
      fundamental studies of methanol metabolism, peroxisome biogenesis and function,
      and also as a microbial cell factory for production of recombinant proteins and
      metabolic engineering towards the goal of high temperature ethanol production.
      RESULTS: We have sequenced the 9 Mbp H. polymorpha DL1 genome and performed whole
      genome analysis for the H. polymorpha transcriptome obtained from both methanol-
      and glucose-grown cells. RNA-seq analysis revealed the complex and dynamic
      character of the H. polymorpha transcriptome under the two studied conditions,
      identified abundant and highly unregulated expression of 40% of the genome in
      methanol grown cells, and revealed alternative splicing events. We have
      identified subtelomerically biased protein families in H. polymorpha, clusters of
      LTR elements at G + C-poor chromosomal loci in the middle of each of the seven H.
      polymorpha chromosomes, and established the evolutionary position of H.
      polymorpha DL1 within a separate yeast clade together with the methylotrophic
      yeast Pichia pastoris and the non-methylotrophic yeast Dekkera bruxellensis.
      Intergenome comparisons uncovered extensive gene order reshuffling between the
      three yeast genomes. Phylogenetic analyses enabled us to reveal patterns of
      evolution of methylotrophy in yeasts and filamentous fungi. CONCLUSIONS: Our
      results open new opportunities for in-depth understanding of many aspects of H.
      polymorpha life cycle, physiology and metabolism as well as genome evolution in
      methylotrophic yeasts and may lead to novel improvements toward the application
      of H. polymorpha DL-1 as a microbial cell factory.

PMID- 24279328
TI  - Male X-linked genes in Drosophila melanogaster are compensated independently of
      the Male-Specific Lethal complex.
AB  - BACKGROUND: In organisms where the two sexes have unequal numbers of X
      chromosomes, the expression of X-linked genes needs to be balanced not only
      between the two sexes, but also between X and the autosomes. In Drosophila
      melanogaster, the Male-Specific Lethal (MSL) complex is believed to produce a 2
      fold increase in expression of genes on the male X, thus restoring this balance.
      RESULTS: Here we show that almost all the genes on the male X are effectively
      compensated. However, many genes are compensated without any significant
      recruitment of the MSL-complex. These genes are very weakly, if at all, affected
      by mutations or RNAi against MSL-complex components. In addition, even the genes
      that are strongly bound by MSL rely on mechanisms other than the MSL-complex for
      proper compensation. We find that long, non-ubiquitously expressed genes tend to
      rely less on the MSL-complex for their compensation and genes that in addition
      are far from High Affinity Sites tend to not bind the complex at all or very
      weakly. CONCLUSIONS: We conclude that most of the compensation of X-linked genes
      is produced by an MSL-independent mechanism. Similar to the case of the MSL
      mediated compensation we do not yet know the mechanism behind the MSL-independent
      compensation that appears to act preferentially on long genes. Even if we observe
      similarities, it remains to be seen if the mechanism is related to the buffering
      that is observed in autosomal aneuploidies.

PMID- 24279329
TI  - The role of protein glycosylation in Alzheimer disease.
AB  - Glycosylation is one of the most common, and the most complex, forms of post
      translational modification of proteins. This review serves to highlight the role
      of protein glycosylation in Alzheimer disease (AD), a topic that has not been
      thoroughly investigated, although glycosylation defects have been observed in AD
      patients. The major pathological hallmarks in AD are neurofibrillary tangles and
      amyloid plaques. Neurofibrillary tangles are composed of phosphorylated tau, and
      the plaques are composed of amyloid beta-peptide (Abeta), which is generated from
      amyloid precursor protein (APP). Defects in glycosylation of APP, tau and other
      proteins have been reported in AD. Another interesting observation is that the
      two proteases required for the generation of amyloid beta-peptide (Abeta), i.e.
      gamma-secretase and beta-secretase, also have roles in protein glycosylation. For
      instance, gamma-secretase and beta-secretase affect the extent of complex N
      glycosylation and sialylation of APP, respectively. These processes may be
      important in AD pathogenesis, as proper intracellular sorting, processing and
      export of APP are affected by how it is glycosylated. Furthermore, lack of one of
      the key components of gamma-secretase, presenilin, leads to defective
      glycosylation of many additional proteins that are related to AD pathogenesis
      and/or neuronal function, including nicastrin, reelin, butyrylcholinesterase,
      cholinesterase, neural cell adhesion molecule, v-ATPase, and tyrosine-related
      kinase B. Improved understanding of the effects of AD on protein glycosylation,
      and vice versa, may therefore be important for improving the diagnosis and
      treatment of AD patients. 

PMID- 24279330
TI  - Palladium-catalyzed arylation of cyclopropanes via directing group-mediated
      C(sp3)-H bond activation to construct quaternary carbon centers: synthesis of cis
      and trans-1,1,2-trisubstituted chiral cyclopropanes.
AB  - Pd(II)-catalyzed tertiary C(sp(3))-H arylation of cyclopropanes via directing
      group-mediated C-H activation for the construction of a chiral quaternary carbon
      center on cyclopropanes using aryl iodides as a coupling partner is reported. The
      arylation had a wide substrate scope and good functional group tolerance,
      including heteroaryl iodides, to provide various chiral arylcyclopropanes with
      the cis- and trans-1,1,2-trisubstituted structures. 

PMID- 24279331
TI  - In situ construction of a coordination zirconocene tetrahedron.
AB  - The current study describes the first in situ synthesis and characterization of a
      new family of cationic coordination tetrahedra of both the V4F4 and V4E6 type,
      which are constructed by a new building block based on a trinuclear zirconocene
      moiety and the dicarboxylate or tricarboxylate anions. 

PMID- 24279332
TI  - Family history of breast cancer predicts breastmilk protein expression.

PMID- 24279333
TI  - Prevalence of nitrite and nitrate contents and its effect on edible bird nest's
      color.
AB  - Edible bird nests (EBNs) are important ethnomedicinal commodity in the Chinese
      community. Recently, But and others showed that the white EBNs could turn red by
      vapors from sodium nitrite (NaNO2) in acidic condition or from bird soil, but
      this color-changing agent remained elusive. The aim of this study was to
      determine the prevalence of nitrite and nitrate contents and its affects on EBN's
      color. EBNs were collected from swiftlet houses or caves in Southeast Asia. White
      EBNs were exposed to vapor from NaNO2 in 2% HCl, or bird soil. The levels of
      nitrite (NO2-) and nitrate (NO3-) in EBNs were determined through ion
      chromatography analysis. Vapors from NaNO2 in 2% HCl or bird soil stained white
      bird nests to brown/red colors, which correlated with increase nitrite and
      nitrate levels. Moreover, naturally formed cave-EBNs (darker in color) also
      contained higher nitrite and nitrate levels compared to white house-EBNs,
      suggesting a relationship between nitrite and nitrate with EBN's color. Of note,
      we detected no presence of hemoglobin in red "blood" nest. Using infrared spectra
      analysis, we demonstrated that red/brown cave-EBNs contained higher intensities
      of C-N and N-O bonds compared to white house-EBNs. Together, our study suggested
      that the color of EBNs was associated with the prevalence of the nitrite and
      nitrate contents.

PMID- 24279334
TI  - Zebrafish: a model vertebrate suitable for the analysis of human genetic
      disorders.
AB  - Zebrafish is a popular model vertebrate because of its conservation of a
      significant number of morphological and physiological processes in vertebrate
      organogenesis. A number of zebrafish mutants isolated from chemical mutagenesis
      screens exhibit characterized morphological defects that often resemble the
      symptoms of human genetic disorders. Recent innovations in genome-editing
      technologies, such as transcription activator-like effector nucleases (TALEN) and
      the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9
      system, enable us to investigate the loss-of-function phenotypes of
      developmentally regulated genes in zebrafish. This review highlights recent
      advances in reverse genetic technologies for zebrafish and presents possible
      applications of zebrafish for the study of human genetic disorders. 

PMID- 24279335
TI  - Targeting Cdc42 with the small molecule drug AZA197 suppresses primary colon
      cancer growth and prolongs survival in a preclinical mouse xenograft model by
      downregulation of PAK1 activity.
AB  - BACKGROUND: Rho GTPases play important roles in cytoskeleton organization, cell
      cycle progression and are key regulators of tumor progression. Strategies to
      modulate increased Rho GTPase activities during cancer progression could have
      therapeutic potential. METHODS: We report here the characterization of a Cdc42
      selective small-molecule inhibitor AZA197 for the treatment of colon cancer that
      was developed based on structural information known from previously developed
      compounds affecting Rho GTPase activation. We investigated the effects of AZA197
      treatment on RhoA, Rac1 and Cdc42 activities and associated molecular mechanisms
      in colon cancer cells in vitro. Therapeutic effects of AZA197 were examined in
      vivo using a xenograft mouse model of SW620 human colon cancer cells. After
      treatment, tumors were excised and processed for Ki-67 staining, TUNEL assays and
      Western blotting to evaluate proliferative and apoptotic effects induced by
      AZA197. RESULTS: In SW620 and HT-29 human colon cancer cells, AZA197 demonstrated
      selectivity for Cdc42 without inhibition of Rac1 or RhoA GTPases from the same
      family. AZA197 suppressed colon cancer cell proliferation, cell migration and
      invasion and increased apoptosis associated with down-regulation of the PAK1 and
      ERK signaling pathways in vitro. Furthermore, systemic AZA197 treatment reduced
      tumor growth in vivo and significantly increased mouse survival in SW620 tumor
      xenografts. Ki-67 staining and tissue TUNEL assays showed that both inhibition of
      cell proliferation and induction of apoptosis associated with reduced PAK/ERK
      activation contributed to the AZA197-induced therapeutic effects in vivo.
      CONCLUSIONS: These data indicate the therapeutic potential of the small-molecule
      inhibitor AZA197 based on targeting Cdc42 GTPase activity to modulate colorectal
      cancer growth.

PMID- 24279336
TI  - Engineering superficial zone chondrocytes from mesenchymal stem cells.
AB  - Recent cartilage engineering efforts have focused on development of zonally
      organized tissue. However, there remains a need for protocols that differentiate
      progenitor populations into chondrocytes of zonal phenotype. Here, we evaluate
      the potential of coculture of bovine mesenchymal stem cells (MSCs) and zonal
      explants of bovine cartilage tissue to drive MSC differentiation to chondrocytes
      with the superficial zone phenotype. Two coculture systems were set up: one
      between alginate encapsulated MSCs and superficial zone cartilage explants, and
      one between MSCs and middle/deep zone cartilage explants. Chondrogenic and
      superficial zone markers were monitored over a 21-day differentiation period via
      gene and protein expression. A control conditioned media study was used to
      determine the impact of communication via soluble factors between cell
      populations during differentiation. At day 21, results show superficial zone
      explant coculture without transforming-growth factor beta3 supplementation
      induces upregulation of chondrogenic gene expression markers SOX9 and type II
      collagen 3.4-fold and 11.4-fold, respectively, over standard chondrogenic control
      media. Further, coculture of MSCs and superficial zone explants can be used to
      upregulate mRNA expression of the superficial zone marker proteoglycan-4 in MSCs
      (1.75-fold over chondrogenic control at day 21), indicating the superficial zone
      chondrocyte phenotype. Gene expression data show middle/deep zone explant and MSC
      coculture did not induce the chondrogenesis observed in superficial zone explant
      coculture. Likewise, poor chondrogenesis was observed in all conditioned media
      groups. Results highlight the importance of superficial zone cartilage and cells
      in guiding stem cell fate and regulating differentiation of MSCs to chondrocytes
      of the superficial zone type. 

PMID- 24279337
TI  - Preoperative workup in the assessment of adrenal incidentalomas: outcome from 282
      consecutive laparoscopic adrenalectomies.
AB  - BACKGROUND: To confirm the efficacy of preoperative workup, the authors analyse
      the results of a multicentre study in a surgical series of patients diagnosed
      with an adrenal incidentaloma. METHODS: The retrospective review of a
      prospectively collected database was conducted. The data was obtained by six
      surgical units operating in the Campania Region, Italy. Five-hundred and six
      (506) adrenalectomies performed between 1993 and 2011 on 498 patients were
      analysed. Final histology in patients with a preoperative diagnosis of
      incidentaloma and studied according to guidelines (230/282 patients group A) was
      compared with final histology coming from patients presenting the same
      preoperative diagnosis but studied not according to guidelines (52/282 patients
      group B). RESULTS: In group A preoperative diagnosis was confirmed at final
      histology in 76/81 (93.8%) cases of subclinical functioning lesions presenting as
      an incidentaloma. The preoperative detection of pheochromocytoma and primary
      adrenocortical cancer (ACC) reached 91.6% and 84.6% respectively. In group B
      conversion rate to open surgery was higher than in group A (p = 0.02). One
      pheochromocytoma was missed at preoperative diagnosis whereas one ACC smaller
      than 4 centimetres (cm) and coming from an incidental lesion was discovered. In
      both groups a significant association between increasing dimensions of
      incidentaloma and cancer has been observed (p = 0.001). CONCLUSIONS: This
      surgical series confirm the high efficacy of suggested guidelines. A significant
      preoperative detection rate of adrenal lesions presenting as incidentaloma is
      observed. The unnecessary number of adrenalectomies performed in understudied
      patients, causing higher morbidity, was not associated to a higher detection rate
      of primary adrenocortical cancer.

PMID- 24279338
TI  - Carcinogenic and inflammatory effects of plutonium-nitrate retention in an
      exposed nuclear worker and beagle dogs.
AB  - PURPOSE: Plutonium-nitrate has a moderately rapid translocation rate from the
      lung to blood stream. Previous studies have shown an unexpected retention of
      soluble plutonium in the beagles and human case studied here. The inflammatory
      responses that may be associated with long-term exposure to ionizing radiation
      were characterized. These pathways include tissue injury, apoptosis, and gene
      expression modifications. Other protein modifications related to carcinogenesis
      and inflammation and the various factors that may play a role in orchestrating
      complex interactions which influence tissue integrity following irradiation were
      investigated. MATERIALS AND METHODS: We have examined numerous lung samples from
      a plutonium-exposed worker, a human control, and a variety of plutonium-exposed
      beagle dogs using immunohistochemistry and quantitative Reverse Transcriptase
      Polymerase Chain Reaction (RT-PCR). RESULTS: The exposed human showed
      interstitial fibrosis in peripheral regions of the lung, but no pulmonary tumors.
      Beagles with similar doses were diagnosed with tumors in bronchiolo-alveolar,
      peripheral and sub-pleural alveolar regions of the lung. The terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed an
      elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris in the
      alveoli and lymph nodes of the beagles but not in the human case. In both the
      beagles and human there were statistically significant modifications in the
      expression of Fas ligand (FASLG), B-cell lymphoma 2 (BCL2), and Caspase 3
      (CASP3). CONCLUSIONS: The data suggests that FASLG, BCL2, CASP3 and apoptosis
      play a role in the inflammatory responses following prolonged plutonium exposure.
      Utilizing these unique tissues revealed which pathways are triggered following
      the internal deposition and long-term retention of plutonium-nitrate in a human
      and a large animal model.

PMID- 24279339
TI  - Structural basis for aggregation mode of oligo-p-phenylene ethynylenes with ionic
      surfactants.
AB  - In this letter, the aggregation modes of two classes of ionic p-phenylene
      ethynylene oligomers with oppositely charged surfactants are studied. The
      location of the ionic side chains was found to influence the type of aggregate
      formed when an equivalent number of surfactant molecules are added to solution.
      When the charged groups were located at the terminal ends of the molecule, strong
      H-aggregates were observed to form. Alternatively, when the ionic groups were
      both located on opposite sides of the central phenyl ring, the formation of J
      aggregates was observed. Interestingly, as the surfactant concentration
      approaches the critical micelle concentration, the weakly bound aggregates are
      dissociated and the absorbance spectrum returns to what is observed in water.
      This study reveals the structural basis for aggregation effects between molecules
      based on the p-phenylene ethynylene backbone, and gives an understanding of how
      to influence the aggregation mode of similar compounds. 

PMID- 24279340
TI  - Effect of isovalent substitution on the thermoelectric properties of the
      Cu2ZnGeSe(4-x)S(x) series of solid solutions.
AB  - Knowledge of structure-property relationships is a key feature of materials
      design. The control of thermal transport has proven to be crucial for the
      optimization of thermoelectric materials. We report the synthesis, chemical
      characterization, thermoelectric transport properties, and thermal transport
      calculations of the complete solid solution series Cu2ZnGeSe(4-x)S(x) (x = 0-4).
      Throughout the substitution series a continuous Vegard-like behavior of the
      lattice parameters, bond distances, optical band gap energies, and sound
      velocities are found, which enables the tuning of these properties adjusting the
      initial composition. Refinements of the special chalcogen positions revealed a
      change in bonding angles, resulting in crystallographic strain possibly affecting
      transport properties. Thermal transport measurements showed a reduction in the
      room-temperature thermal conductivity of 42% triggered by the introduced
      disorder. Thermal transport calculations of mass and strain contrast revealed
      that 34% of the reduction in thermal conductivity is due to the mass contrast
      only and 8% is due to crystallographic strain.

PMID- 24279341
TI  - From understanding to prediction: gold- and platinum-based pi-acid catalysis for
      target oriented synthesis.
AB  - During the last century, conceptual advances in organometallic chemistry were
      often rapidly embraced by target oriented synthesis. Feedback provided by such
      preparative scrutiny has greatly benefitted method development; particularly
      prominent are examples from the entire cross coupling arena, as well as olefin
      metathesis. Seen against this backdrop, it is somewhat surprising that the
      explosive growth of research into pi-acid catalysis has not yet yielded a
      matching number of implementations into the synthesis of structurally complex
      targets of biological significance. In contrast to the massive output of
      methodological and mechanistic investigations, few studies illustrate the
      strategic use of gold, silver, or platinum catalysis in late stages of such
      multistep endeavors. These elaborate and highly precious compounds demand utmost
      confidence in the reliability and robustness of the method to be applied. In this
      Account, we analyze the possible reasons for this imbalance, after a short
      summary of the conceptual basis of carbophilic activation of pi-bonds with the
      aid of soft transition metal cations or complexes. We pinpoint mechanistic
      subtleties, which, at least in part, produce a great deal of structural diversity
      but can jeopardize predictive power. With the advances in the understanding of pi
      acid catalyzed processes in general, however, this uncertainty is gradually
      vanishing and the entire field is transitioning from comprehension to prediction.
      This is expected to foster advanced applications, while recent progress in
      asymmetric gold catalysis further improves the preparative significance. The
      presented work in this Account illustrates our own commitment to the field as
      well as our growing confidence in the maturity of platinum and gold catalysis.
      The carbophilic activation of pi-bonds, particularly of alkynes, provides a
      method to manipulate functional groups that is orthogonal to traditional carbonyl
      chemistry. We illustrate this notion by presenting a new approach to
      hydroxypyrone derivatives that has enabled the total synthesis of the fragile
      polyunsaturated cyclophane derivative neurymenolide A. The synthesis of the
      pyrrole alkaloid streptorubin by an enyne cycloisomerization is equally
      instructive. In addition, different manifestations of transannular hydroxyl
      addition reactions across alkyne partners mark the late stages of our conquests
      of amphidinolide F, polycavernoside A, and spirastrellolide F. Together with a
      few model studies and a personal selection of recent highlights from other
      groups, these examples augur well for future applications of pi-acid catalysts in
      the realm of target oriented synthesis. 

PMID- 24279342
TI  - New anti-inflammatory triterpene from the root of Ricinus communis.
AB  - Liquid-liquid partitioning of Ricinus communis root methanol extract resulted in
      enrichment of compounds. Purification of the n-hexane fraction led to the
      isolation and characterisation of two triterpenes: one known compound lupeol (1)
      and a new diketone pentacyclic triterpene named as erandone (urs-6-ene-3,16
      dione) (2), from the plant. Their structures were determined by various
      spectroscopic techniques. Crude methanolic, enriched n-hexane fraction and
      isolates at doses 100 mg/kg p.o. exhibited significant (P < 0.001) anti
      inflammatory activity in carrageenan-induced hind paw oedema model.

PMID- 24279343
TI  - Brucellosis seroprevalence in Bali cattle with reproductive failure in South
      Sulawesi and Brucella abortus biovar 1 genotypes in the Eastern Indonesian
      archipelago.
AB  - BACKGROUND: Brucellosis is a major cause of infertility and reproductive failure
      in livestock. While cattle in the Eastern Indonesian archipelago suffers from
      reproductive problems information on bovine brucellosis in the region is
      fragmentary. The control of brucellosis requires a major and prolonged effort and
      confirmation of the infection by isolation with detailed knowledge of the spread
      of the infection is essential when planning a control program. RESULTS:
      Serological investigation of Brucella infection in beef cattle tended under
      extensive farming conditions revealed a high seroprevalence (19.3%; 95% CI, 17
      22) in the compliment fixation tests. The results of a rapid and simple field
      test correlated well with the Rose Bengal test (kappa, 0.917) and indicated an
      acceptable sensitivity (87.5%) and specificity (98.1%) compared with the
      complement fixation test. Reproductive failure was reported for 39.0% of the cows
      with a loss of calves due to abortion or early death amounting to 19.3%. Past
      reproductive failure did not, however, correlate with seropositivity in the
      complement fixation test (RP = 1.21; P = 0.847). B. abortus biovar 1 was freshly
      isolated from the hygromas of two cows and together with thirty banked isolates
      collected since 1990 from different parts of Sulawesi and Timor eight related
      genotypes could be distinguished with one genotype being identical to that of an
      isolate (BfR91) from Switzerland. The Indonesian genotypes formed together with
      BfR91 and one African and one North American isolate a distinct branch on the B.
      abortus biovar 1 dendogram. CONCLUSIONS: Bovine brucellosis appears to be
      widespread in the Eastern Indonesian archipelago and calls for urgent
      intervention. The fresh isolation of the pathogen together with the observed high
      seroprevalence demonstrates the presence and frequent exposure of cattle in the
      area to the pathogen. The application of a rapid and simple field test for
      brucellosis could be very useful for the quick screening of cattle at the pen
      side.

PMID- 24279344
TI  - Preliminary report of the relationship between experience of death of a relative,
      illness perception, and psychological outcome among BRCA carriers.
AB  - With recent advances in mapping the genetic mutations involved in breast cancer
      and the availability of genetic testing, it has become necessary to explore the
      psychological consequences of women who have tested positive for the gene
      mutations involved in breast cancer (BReast CAncer gene one and two, BRCA1/2).
      Findings regarding psychological consequences of positive results in genetic
      testing for breast cancer are ambiguous and insufficient. The aim of the current
      study was to explore the relationship between experience of the death of a
      relative due to breast cancer, perception of the illness, distress, and well
      being among BRCA1/2 mutation women carriers. Forty asymptomatic carriers who
      attended BRCA1/2 clinics in Israel completed self-administered questionnaires
      assessing socio-demographic variables, illness perception, and well-being. It was
      found that experiencing the death of a relative as a result of breast cancer was
      significantly correlated with illness perception. Carriers who experienced the
      death of a relative perceived breast cancer as having a stronger identity (i.e.
      as having severe symptoms), dire consequences, and as being uncontrollable in
      comparison to carriers who had not experienced the death of a relative.
      Nevertheless, psychological distress and well-being were not found to be
      significantly correlated to either an experience of death of a relative as a
      result of breast cancer or to illness perception. Implications and limitations
      are discussed in light of these findings. Among these is the need to consider the
      illness perception of healthy BRCA carriers women.

PMID- 24279345
TI  - Rapid transfer of endothelial cell sheet using a thermosensitive hydrogel and its
      effect on therapeutic angiogenesis.
AB  - In this study, thermosensitive hydrogels incorporated with multiple cell
      interactive factors were developed as a substrate to form monolayer of human
      umbilical vein endothelial cells (HUVECs) that can be detached and transferrable
      to target sites as a cell-sheet in response to temperature change. The cell
      adhesive peptide (RGD) and growth factor (bFGF) covalently incorporated within
      the hydrogel significantly enhanced adhesion and proliferation of HUVECs,
      allowing for the formation of their confluent monolayer. Meanwhile, the precisely
      controllable change in the size of the hydrogels was observed by a repeated
      increase and decrease in temperature from 37 to 4  degrees C. By exploiting this
      unique behavior, the detachment and transfer of HUVEC sheet confluently cultured
      at 37  degrees C was rapidly induced within 10 min by expansion of the hydrogels
      when the temperature was decreased to 4  degrees C. The transferred cell sheet
      was highly viable and maintained robust cell-cell junction. Finally, the process
      of cell sheet transfer was directly applied onto an ischemic injury in the hind
      limb of mice. The transplanted HUVECs as a sheet retarded tissue necrosis over 14
      days in comparison with that of direct injection of the same number of cells. Our
      results suggest that the developed multifunctional Tetronic-tyramine hydrogels
      could serve as an ideal substrate to modulate the formation of an endothelial
      cell layer that could potentially be utilized to treat peripheral arterial
      disease. 

PMID- 24279346
TI  - Ultrahigh performance liquid chromatography analysis of volatile carbonyl
      compounds in virgin olive oils.
AB  - The enzymatic and chemical oxidation reaction in olive oil produces many volatile
      carbonyl compounds that contribute to the complex flavor of olive oil. A novel
      ultrahigh performance liquid chromatography (UHPLC) method with dynamic headspace
      sampling and 2,4-dinitrophenylhydrazine (DNPH) derivatization were established to
      determine the volatile carbonyls in virgin olive oil. Quantification of nine
      characteristic carbonyls (acetone, hexanal, E-2-hexenal, octanal, E-2-octenal,
      nonanal, E-2-nonenal, E,E-2,4-nonadienal, and E,E-2,4-decadienal) was achieved
      using cyclopentanal as an internal standard. This method provides comparable
      linearity (R(2) = 0.9917-1.0000) and repeatability (less than 7.6% relative
      standard deviations) with solid phase microextraction gas chromatography (SPME
      GC). The relative standard deviations (%RSD) of all applied carbonyl standards
      were lower than 7.6%. The limits of detection (LOD) and quantification (LOQ) were
      in the ranges of 1.6-150.1 and 4.8-906.1 MUg/kg. The recoveries obtained for
      olive oil samples were in the range of 81.0-115.3%. To show the potential of this
      method on the quantification of other volatile carbonyls that were not included
      in this study, GC-electron ionization mass spectrometry (GC-EI/MS) was employed
      to identify the derivatized carbonyls (carbonyl (2,4-DNPH) hydrazones) while peak
      assignments were made on the basis of elution sequences and peak areas. This
      method provided feasibility of using LC to determine volatile carbonyls in oil
      matrices, which can be applied to exam the degree of lipid oxidation and evaluate
      the sensory properties of VOO and other edible oils. 

PMID- 24279347
TI  - Biochemical and functional characterization of SpdA, a 2', 3'cyclic nucleotide
      phosphodiesterase from Sinorhizobium meliloti.
AB  - BACKGROUND: 3', 5'cAMP signaling in Sinorhizobium meliloti was recently shown to
      contribute to the autoregulation of legume infection. In planta, three adenylate
      cyclases CyaD1, CyaD2 and CyaK, synthesizing 3', 5'cAMP, together with the Crp
      like transcriptional regulator Clr and smc02178, a gene of unknown function, are
      involved in controlling plant infection. RESULTS: Here we report on the
      characterization of a gene (smc02179, spdA) at the cyaD1 locus that we predicted
      to encode a class III cytoplasmic phosphodiesterase.First, we have shown that
      spdA had a similar pattern of expression as smc02178 in planta but did not
      require clr nor 3', 5'cAMP for expression.Second, biochemical characterization of
      the purified SpdA protein showed that, contrary to expectation, it had no
      detectable activity against 3', 5'cAMP and, instead, high activity against the
      positional isomers 2', 3'cAMP and 2', 3'cGMP.Third, we provide direct
      experimental evidence that the purified Clr protein was able to bind both 2',
      3'cAMP and 3', 5'cAMP in vitro at high concentration. We further showed that Clr
      is a 3', 5'cAMP-dependent DNA-binding protein and identified a DNA-binding motif
      to which Clr binds. In contrast, 2', 3'cAMP was unable to promote Clr specific
      binding to DNA and activate smc02178 target gene expression ex planta.Fourth, we
      have shown a negative impact of exogenous 2', 3'cAMP on 3', 5'cAMP-mediated
      signaling in vivo. A spdA null mutant was also partially affected in 3', 5'cAMP
      signaling. CONCLUSIONS: SpdA is a nodule-expressed 2', 3' specific
      phosphodiesterase whose biological function remains elusive. Circumstantial
      evidence suggests that SpdA may contribute insulating 3', 5'cAMP-based signaling
      from 2', 3' cyclic nucleotides of metabolic origin.

PMID- 24279348
TI  - Exploring the potential of Burkholderia sacchari to produce
      polyhydroxyalkanoates.
AB  - AIM: Evaluation of the capability of Burkholderia sacchari to incorporate
      different monomers into polyhydroxyalkanoates (PHA). METHODS AND RESULTS: Thirty
      different carbon sources were evaluated as cosubstrates for B. sacchari growing
      on glucose with the intention to promote the incorporation of different monomers
      into the PHA produced by this species. With odd-numbered fatty acids,
      incorporation of the 3HV monomer was achieved, up to 65 mol% in the case of
      valerate. With 4-hydroxybutyrate, incorporation of 4HB was obtained, representing
      9.1 mol%. With hexanoic acid, the production of P3HB-co-3HHx was achieved,
      containing up to 1.6 mol% of 3HHx. The molar fraction of 3HHx was found to be
      dependent on the ratio of glucose to hexanoic acid supplied. Metabolic flux
      analysis revealed a high efficiency of B. sacchari in converting carbon sources
      into P3HB-co-3HHx. Nevertheless, hexanoic acid was only poorly converted to 3HHx.
      CONCLUSIONS: Burkholderia sacchari is able to incorporate 3HV, 4HB and 3HHx in
      PHA containing mainly 3HB. The 3HHx content of P3HB-co-3HHx can be controlled by
      varying the glucose to hexanoic acid ratio. Burkholderia sacchari is highly
      efficient in converting carbon sources into PHA; however, only 2% of the hexanoic
      acid supplied could be converted to 3HHx. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report describing an approach to modulate the composition of
      P3HB-co-3HHx produced by bacteria using mixtures of carbohydrate and hexanoic
      acid as carbon source.

PMID- 24279350
TI  - Rh(III)-catalyzed olefination of N-sulfonyl imines: synthesis of ortho-olefinated
      benzaldehydes.
AB  - Rh(III)-catalyzed olefination of N-sulfonyl imines using acrylates and styrenes
      has been achieved for the synthesis of ortho-olefinated benaldehydes. This
      reaction proceeds via a chelation assisted C-H olefination/in situ hydrolysis
      process. 

PMID- 24279349
TI  - The alkaline hydrolysis of sulfonate esters: challenges in interpreting
      experimental and theoretical data.
AB  - Sulfonate ester hydrolysis has been the subject of recent debate, with
      experimental evidence interpreted in terms of both stepwise and concerted
      mechanisms. In particular, a recent study of the alkaline hydrolysis of a series
      of benzene arylsulfonates (Babtie et al., Org. Biomol. Chem. 10, 2012, 8095)
      presented a nonlinear Bronsted plot, which was explained in terms of a change
      from a stepwise mechanism involving a pentavalent intermediate for poorer leaving
      groups to a fully concerted mechanism for good leaving groups and supported by a
      theoretical study. In the present work, we have performed a detailed
      computational study of the hydrolysis of these compounds and find no
      computational evidence for a thermodynamically stable intermediate for any of
      these compounds. Additionally, we have extended the experimental data to include
      pyridine-3-yl benzene sulfonate and its N-oxide and N-methylpyridinium
      derivatives. Inclusion of these compounds converts the Bronsted plot to a
      moderately scattered but linear correlation and gives a very good Hammett
      correlation. These data suggest a concerted pathway for this reaction that
      proceeds via an early transition state with little bond cleavage to the leaving
      group, highlighting the care that needs to be taken with the interpretation of
      experimental and especially theoretical data. 

PMID- 24279351
TI  - Gender-related association of brain-derived neurotrophic factor gene 196A/G
      polymorphism with Alzheimer's disease--a meta-analysis including 6854 cases and
      6868 controls.
AB  - Epidemiological studies have evaluated the associations between brain-derived
      neurotrophic factor (BDNF) 196A/G gene polymorphism and Alzheimer's disease (AD)
      risk. However, the results remain inconclusive. Sexually dimorphic effect of the
      polymorphism of BDNF 196A/G in AD patients had been proposed previously,
      specifically in female group. As more cases were reported, therefore, we
      performed a meta-analysis of published case-control studies to better understand
      these results. We systematically searched online databases of Embase, PubMed and
      Web of Science, as well as hand searching of the references of identified
      articles and meeting abstracts. Review Manager (Version 5.2.4) and Stata software
      (Version 12.0) were used for statistical analyses. The pooled odds ratios (ORs)
      with 95% confidence intervals (95% CIs) were calculated. A total of 23
      publications including 25 studies were identified and entered the analysis. No
      significant association was observed in overall population, as well as subgroups
      stratified by ethnicity (Caucasian and Asian). However, when stratified by
      gender, significant association was observed just in female subgroup (A allele
      vs. G allele: OR = 1.15, 95% CI = 1.06-1.25; A/A vs. G/G: OR = 1.29, 95% CI =
      1.06-1.57; A/A + A/G vs. G/G: OR = 1.30, 95% CI = 1.11-1.53). This meta-analysis
      confirmed the gender-related association between BDNF 196A/G polymorphism and AD
      risk, which may indicate a certain effect of female hormone on progression of the
      disease. Larger sample size and more studies with homogeneous AD patients and
      well-matched controls are needed in future.

PMID- 24279352
TI  - Recombinant insulin-like growth factor-1 activates satellite cells in the mouse
      urethral rhabdosphincter.
AB  - BACKGROUND: The goal of this study is to demonstrate the efficacy of a new method
      for the treatment of urinary incontinence by stimulation of urethral
      rhabdosphincter satellite cells. We show that satellite cells do exist in the
      sphincter muscle of retired male mice breeders by staining for c-Met, a satellite
      cell specific protein. Once activated by recombinant mouse Insulin-like Growth
      Factor-1(rIgf-1), the satellite cells develop into muscle cells within the
      rhabdosphincter thereby potentially strengthening it. METHODS: 20 MUl (1 MUg/MUl)
      of rIgf-1 was surgically injected directly into the urethral wall of retired male
      mouse breeders. Mice injected with phosphate buffered saline (PBS) were used as
      controls. 4 weeks later, urethras were harvested and serially-sectioned through
      the sphincter for routine hematoxylin-eosin staining as well as
      immunohistochemical staining with satellite cell specific anti-c-Met antibody and
      proliferation specific anti-Ki-67 antibody. RESULTS: Anti-c-Met antibody positive
      cells (c-Met+) were identified in the rhabdosphincter. c-Met+ cells increased by
      161.8% relative to controls four weeks after rIGF-1 injection. Anti- Ki-67
      antibody positive cells were identified and characterized as cells with centrally
      located nuclei in striated muscle bundles of rIGF-1 treated animals. CONCLUSIONS:
      Satellite cells in the mouse rhabdosphincter can be activated by rIGF-1
      treatment, which subsequently are incorporated into existing skeletal muscle
      bundles. Using this approach, the rhabdosphincter can be induced to regenerate
      and potentially strengthen via satellite cell activation and likely improve
      urinary continence.

PMID- 24279353
TI  - pH-dependent hydrolase, glutaminase, transpeptidase and autotranspeptidase
      activities of Bacillus subtilis gamma-glutamyltransferase.
AB  - gamma-Glutamyltransferases (gamma-GTs) are heterodimeric enzymes that catalyze
      the transfer of a gamma-glutamyl group from a donor species to an acceptor
      molecule in a transpeptidation reaction through the formation of an intermediate
      gamma-glutamyl enzyme. In our search for a gamma-GT from a generally recognized
      as safe microorganism suitable for the production of gamma-glutamyl derivatives
      with flavor-enhancing properties intended for human use, we cloned and
      overexpressed the gamma-GT from Bacillus subtilis. In this study, we report the
      behavior of B. subtilis gamma-GT in reactions involving glutamine as the donor
      compound and various acceptor amino acids. The common thread emerging from our
      results is a strong dependence of the hydrolase, transpeptidase and
      autotranspeptidase activities of B. subtilis gamma-GT on pH, also in relation to
      the pKa of the acceptor amino acids. Glutamine, commonly referred to as a poor
      acceptor molecule, undergoes rapid autotranspeptidation at elevated pH, affording
      oligomeric species, in which up to four gamma-glutamyl moieties are linked to a
      single glutamine. Moreover, we found that D-glutamine is also recognized both as
      a donor and as an acceptor substrate. Our results prove that the B. subtilis
      gamma-GT-catalyzed transpeptidation reaction is feasible, and the observed
      activities of gamma-GT from B. subtilis could be interpreted in relation to the
      known ability of the enzyme to process the polymeric material gamma-polyglutamic
      acid.

PMID- 24279354
TI  - Xmrk-induced melanoma progression is affected by Sdf1 signals through Cxcr7.
AB  - Chemokine signals mediated by Sdf1/Cxcl12 through the chemokine receptor Cxcr4
      are thought to play an instructive role in tumor migration and organ-specific
      metastasis. We have used a small aquarium fish model to contribute to a better
      understanding of how the course of melanoma development is influenced by Sdf1
      signals in vivo. We studied oncogene-induced skin tumor appearance and
      progression in the transgenic medaka (Oryzias latipes) melanoma model. Similar to
      humans, invasive medaka melanomas show increased levels of sdf1, cxcr4, and cxcr7
      gene expression. Stable transgenic fish lines overexpressing sdf1 exclusively in
      pigment cells showed a reduction in melanoma appearance and progression.
      Remarkably, diminished levels of functional Cxcr7, but not of Cxcr4b, resulted in
      strongly reduced melanoma invasiveness and a repression of melanoma. Our results
      thereby indicate that Sdf1 signals via Cxcr7 are able to constrain melanoma
      growth in vivo and that these signals influence tumor outcome. 

PMID- 24279355
TI  - Genotypic variation in tomatoes affecting processing and antioxidant attributes.
AB  - Tomatoes are widely consumed either raw or after processing and can provide a
      significant proportion of the total antioxidants in the diet associated with
      beneficial health properties. Over the last two or three decades an increasing
      interest for processing and antioxidant attributes in tomatoes has arisen. The
      screening of processing attributes of tomatoes is subject of a large number of
      articles; however, special interest has been addressed to the biochemical
      composition. The postharvest and industrial processing of tomato in tomato-based
      products includes several steps. Processing and antioxidant characteristics of
      the raw fruit are important considering the processing steps and final product.
      To respond to consumer and industrial complaints, breeders should know the range
      of genetic variability available in tomato resources, including local genotypes,
      for improving the mentioned attributes. Characterization and conservation of
      traditional and modern varieties is a major goal for their preservation and
      utilization. The bioactive contents have an impact on the processed destines so
      their stability must be contemplated while selecting the tomato fruits for
      processing. The endeavor of this review was to examine comprehensively the
      variation in processing and antioxidant attributes among tomatoes. Role of tomato
      peel in terms of bioactive contents and information on high pigment (hp) tomato
      mutants are also touched to some extent. Probably, patterns of variation
      identified/discussed in this paper would give impetus for planning breeding
      strategies to develop and improve the new processing cultivars with good
      antioxidant status.

PMID- 24279356
TI  - Identification and partial characterization of a bacteriocin-like inhibitory
      substance (BLIS) from Lb. Bulgaricus K41 isolated from indigenous yogurts.
AB  - Forty-two strains of Lactobacillus bulgaricus isolated from locally made yogurts
      were examined and compared for bacteriocin producing ability using spot on lawn
      assay which improved by taking photo and image processing. Lb. bulgaricus K41
      exhibited the highest inhibition level against indicators. K41 Bacteriocin-like
      inhibitory substance is sensitive to proteolytic enzymes (proteinase K, pepsin,
      and trypsin) but alpha-amylase makes slight reduction in its activity and it is
      resistant to lipase. This antibacterial peptide is extremely heat-stable (121 
      degrees C for 15 min) and remains active over a wide pH range (pH = 2 to 10);
      also nonionic detergents (Tween-20, Tween-80, and Triton X100) showed no effect
      on its activity. The inhibitory spectrum is against Gram-positive bacteria
      (except Staphylococcus aureus) with extremely antilisterial activity and it is
      almost ineffective against Gram-negative bacteria. The mode of its action was
      identified as bactericidal against Listeria monocytogenes. The properties of K41
      bacteriocin-like inhibitory substance add to its safety as a biopreservative
      produced by a generally recognized as safe (GRAS) bacterium suggesting it can be
      used in hurdle technology for ready-to-eat foods as one of the main sources of
      Listeria contaminations. 

PMID- 24279357
TI  - Substituent-dependent spin-density distribution and coexistence of Fe 3d and pi
      spins on ferrocene-tetrathiafulvalene hybrids.
AB  - Ferrocene (Fc) and tetrathiafulvalene (TTF) moieties were incorporated into novel
      hybrid molecules of structure FcS4TTF(R)2 (R = CF3 and SMe). [FcS4TTF(R)2](*+)
      exhibited R-dependent spin-density distribution, and [FcS4TTF(CF3)2](**2+) showed
      the coexistence of Fc-centered Fe 3d and TTF-centered pi spins. The solid-state
      molecular structures in different oxidation states reflect their characteristic
      spin states. 

PMID- 24279358
TI  - Morphological and anatomical determinants of mesophyll conductance in wild
      relatives of tomato (Solanum sect. Lycopersicon, sect. Lycopersicoides;
      Solanaceae).
AB  - Natural selection on photosynthetic performance is a primary factor determining
      leaf phenotypes. The complex CO2 diffusion path from substomatal cavities to the
      chloroplasts - the mesophyll conductance (g(m)) - limits photosynthetic rate in
      many species and hence shapes variation in leaf morphology and anatomy. Among
      sclerophyllous and succulent taxa, structural investment in leaves, measured as
      the leaf dry mass per area (LMA), has been implicated in decreased gm . However,
      in herbaceous taxa with high g(m), it is less certain how LMA impacts CO2
      diffusion and whether it significantly affects photosynthetic performance. We
      addressed these questions in the context of understanding the ecophysiological
      significance of leaf trait variation in wild tomatoes, a closely related group of
      herbaceous perennials. Although g(m) was high in wild tomatoes, variation in g(m)
      significantly affected photosynthesis. Even in these tender-leaved herbaceous
      species, greater LMA led to reduced g(m). This relationship between g(m) and LMA
      is partially mediated by cell packing and leaf thickness, although amphistomy
      (equal distribution of stomata on both sides of the leaf) mitigates the effect of
      leaf thickness. Understanding the costs of increased LMA will inform future work
      on the adaptive significance of leaf trait variation across ecological gradients
      in wild tomatoes and other systems.

PMID- 24279359
TI  - 'Tis the season: give the gift of palliative care.

PMID- 24279363
TI  - Myasthenia gravis.
AB  - Myasthenia gravis (MG) is a chronic neuromuscular disorder characterized by
      fluctuating skeletal muscle weakness and fatigue. This rare autoimmune condition
      can present a diagnostic challenge for the advanced practice nurse (APN). Because
      of its low incidence in clinical practice and frequently unrecognized symptoms, a
      delay of 1 to 2 years prior to diagnosis is not uncommon. Recognition of the
      clinical features is a key component of prompt diagnosis. To avoid delay in
      treatment, APNs should be aware of variations in MG symptoms and the tools used
      to confirm a suspected diagnosis. Because patients benefit from the care of
      neuromuscular specialists, APNs are not expected to be experts within MG
      treatment. But knowledge of general treatment principles affords the APN an
      opportunity to collaborate with the neuromuscular specialist to provide care for
      patients with MG. Using an individual example, this article reviews the
      experience of an older adult with MG from clinical presentation through
      treatment.

PMID- 24279365
TI  - The examination of nursing work through a role accountability framework.
AB  - AIM: To use work analysis data to describe the amount of time registered nurses
      (RNs) and health care aides (HCA) spent on key clinical role accountabilities and
      other work activities. BACKGROUND: Health care providers are not effectively
      utilized. To improve their efficiency and effectiveness, it is necessary to
      understand how nursing providers enact their role accountabilities. METHOD: Using
      palm pilot Function Analysis technology, observers recorded the activities of 35
      registered nurse and 17 health care aides shifts on a second-by-second basis over
      5 days. Work activities were classified using the Nursing Role Effectiveness
      Model, which conceptualizes nursing practice in terms of clinical role
      accountabilities. RESULT: The registered nurses spent a considerable amount of
      time on bio-medical assessment/surveillance, relatively little time was spent on
      patient and family psycho-social-cultural-spiritual assessment/surveillance and
      support. CONCLUSION: Unlike other work sampling studies, this research project
      examined nursing work within a role accountability framework; an important first
      step in the call for the measurement of the impact of nursing care. IMPLICATIONS
      FOR NURSING MANAGEMENT: Changes to how registered nurses and health care aides
      enact their role will require a clear vision by unit managers and their staff of
      their role accountabilities, and the gap between ideal and actual practice.

PMID- 24279366
TI  - Dosimetric analysis of fathead minnow (Pimephales promelas, Rafinesque, 1820)
      exposed via ingestion to environmentally relevant activities of Ra-226 for two
      years.
AB  - PURPOSE: To assess the dosimetry of Ra-226 in a two-year chronic ingestion study
      in laboratory maintained fathead minnow fed environmentally relevant levels of
      the isotope known to occur in gut contents of fish from a uranium mining area.
      METHODS: Fish were established on reconstituted commercial fish food containing
      10 mBq-10 Bq Ra-226.g(- 1) dry food. The fish were sampled at 1, 6, 18 and 24
      months and the Ra-226 levels in the whole fish were directly determined using
      measurement performed using inorganic mass spectrometry. Pilot experiments using
      higher doses were also done during development of a liquid scintillation
      detection system which support some data. RESULTS: The data show that after 1
      month the levels of accumulation in the fish were below detection. At 6 months
      there was an activity dependent accumulation which was relatively higher in the
      low activity groups. By 18 and 24 months the radium was very low in all groups -
      well below 6 month levels suggesting considerable loss of radium from the fish.
      These data were confirmed in a small and shorter study using higher dietary
      activities. The highest dose calculated for any measurement point was 16 MUGy.h(-
      1) in the 6-month-old fish fed the diet containing 10 Bq.g(- 1). CONCLUSIONS: We
      conclude that environmentally relevant levels of Ra-226 have a maximum impact at
      early time-points when the fish are still growing. After that they appear to
      depurate accumulated radium. In terms of environmental impact, the maximum
      accumulation peaks at the age where fish could be spawning but is extremely low
      leading to MUGy.year(- 1) doses even after exposure to the high activity diets.

PMID- 24279367
TI  - Very low dose gamma irradiation stimulates gaseous exchange and carboxylation
      efficiency, but inhibits vascular sap flow in groundnut (Arachis hypogaea L.).
AB  - PURPOSE: An experiment was carried out to determine the effect of low dose gamma
      radiation on germination, plant growth, nitrogen and carbon fixation and carbon
      flow and release characteristics of groundnut. MATERIALS AND METHODS: Dry seeds
      of groundnut variety Trombay groundnut 37A (TG 37A), a radio mutant type
      developed by Bhabha Atomic Research Centre (BARC), Mumbai, India, were subjected
      to the pre-sowing treatment of gamma radiation within low to high dose
      physiological range, i.e., 0.0, 0.0082, 0.0164. 0.0328, 0.0656, 0.1312, 5, 25,
      100, 500 Gray (Gy) from a cobalt source ((60)Co). Observations were recorded for
      the radiation effect on percentage germination, vigour, gas exchange attributes
      such as photosynthetic rate, stomatal conductance and transpiration rate,
      chlorophyll content, root exudation in terms of (14)C release, vascular sap flow
      rate and activities of rate defining carbon and nitrogen assimilating enzymes
      such as ribulose-1,5-bisphosphate carboxylase (rubisco) and nitrate reductase
      (NR). RESULTS: Seed germination was increased by 10-25% at the lower doses up to
      5 Gy while the improvement in plant vigour in the same dose range was much higher
      (22-84%) than the unirradiated control. For radiation exposure above 5 Gy, a dose
      dependent decline in germination and plant vigour was measured. No significant
      effect was observed on the photosynthesis at radiation exposure below 5 Gy but
      above 5 Gy dose there was a decline in the photosynthetic rate. Stomatal
      conductance and transpiration rate, however, were only inhibited at a high dose
      of 500 Gy. Leaf rubisco activity and NR activities remained unaffected at all the
      investigated doses of gamma irradiation. Mean root exudation and sap flow rate of
      the irradiated plants, irrespective of the dose, was reduced over the
      unirradiated control more so in a dose-dependent manner. CONCLUSIONS: Results
      indicated that a very low dose of gamma radiation, in centigray to gray range,
      did not pose any threat and in fact stimulated metabolic functions in such a way
      to aid growth and development of groundnut plants. It further showed that the
      radiation threshold for the gas exchange traits and rubisco activity, which
      ultimately determine the plant health and yield, were higher than compared to the
      other metabolic attributes and were well beyond 500 Gy and that the dose range
      above 500 Gy should be targeted to measure lethal effects of radiation on carbon
      assimilation attributes in leguminous crops, in general, and groundnut in
      particular.

PMID- 24279368
TI  - Burnout in Australian psychologists: correlations with work-setting, mindfulness
      and self-care behaviours.
AB  - Burnout is an inherent risk for those working as mental health professionals,
      given the nature of their work. Due to recent Medicare changes in Australia,
      private practice psychologists were suspected to face similar burnout risks as
      non-private practitioners. The aim of the present study was to investigate the
      relationships among burnout in Australian psychologists, work-setting and years
      of experience in that setting, mindfulness and career-sustaining behaviours
      (CSBs). 145 Females and 22 male Australian registered psychologists, with a mean
      age of 42.47 years (SD = 11.64, range 24-68), were surveyed to determine work
      setting, mindfulness, burnout and preferences for CSBs. High levels of burnout
      were reported among Australian psychologists. No significant difference in
      burnout between psychologists working in private-practice and non-private
      practice settings was found. There was a strong negative relationship between
      mindfulness and burnout and there was a low but significant negative relationship
      between years of experience in current work-setting and burnout levels. CSB
      preferences only had weak relationships with burnout, which decreased after
      controlling for mindfulness. Several CSBs that had a detrimental relationship
      with burnout were identified and may be worthy of further investigation.
      Developing strategies to increase mindfulness may prevent burnout in Australian
      psychologists.

PMID- 24279369
TI  - Mycobiota and toxigenic Penicillium species on two Spanish dry-cured ham
      manufacturing plants.
AB  - The present study reports the natural mycobiota occurring in dry-cured hams, and
      in particular on the incidence of mycotoxin-producing fungi. A total of 338
      fungal colonies were isolated from three stages of production, these being the
      post-salting, ripening and aging stages in two manufacturing plants. The results
      show that fungi were more frequently isolated from the aging stage and that the
      predominant filamentous fungal genus isolated was Penicillium. Seventy-four of
      the 338 fungal strains were selected for identification at the species level by
      using morphological criteria and internal transcribed spacers sequencing. Of the
      74 fungal strains, 59 were Penicillium strains. Sixteen Penicillium species were
      identified, with P. commune (24 strains) and P. chrysogenum (13 strains) being
      the most abundant. The potential ability to produce cyclopiazonic acid (CPA) and
      ochratoxin A (OTA) was studied by isolating the culture followed by HPLC analysis
      of these mycotoxins in the culture extracts. The results indicated that 25
      (33.7%) of the 74 fungal strains produced CPA. Worth noting is the high
      percentage of CPA-producing strains of P. commune (66.6%) of which some strains
      were highly toxigenic. P. polonicum strains were also highly toxigenic. With
      respect to OTA-producing fungi, a low percentage of fungal strains (9.5%) were
      able to produce OTA at moderate levels. OTA-producing fungi belonged to different
      Penicillium species including P. chrysogenum, P. commune, P. polonicum and P.
      verrucosum. These results indicate that there is a possible risk factor posed by
      CPA and OTA contamination of dry-cured hams. 

PMID- 24279370
TI  - Closer to photosystem II: a Co4O4 cubane catalyst with flexible ligand
      architecture.
AB  - We introduce the novel Co4O4 complex [Co(II)4(hmp)4(MU-OAc)2(MU2-OAc)2(H2O)2] (1)
      (hmp = 2-(hydroxymethyl)pyridine) as the first Co(II)-based cubane water
      oxidation catalyst. Monodentate acetate and aqua ligands lend the flexible
      environment of 1 closest resemblance to photosystem II among its tetranuclear
      mimics to date. Visible-light-driven catalytic activity of 1 increases with pH
      value through aqua ligand deprotonation. The Co(II) core combines robustness and
      stability with flexibility through a new type of water-oxidation mechanism via
      mobile ligands. 

PMID- 24279371
TI  - Maternal risk factors in the origin of isolated hypospadias: a population-based
      case-control study.
AB  - The birth prevalence of hypospadias increased in Hungary during the last decades,
      thus the aim of this study was to analyze the possible role of maternal risk
      factors in the origin of isolated hypospadias (IHS). The incidence/prevalence of
      acute and chronic maternal diseases with related drug treatments were compared in
      the mothers of cases with IHS, population controls without defect and malformed
      controls affected with other isolated abnormalities in the population-based
      Hungarian Case-Control Surveillance of Congenital Abnormalities including 3038
      cases with IHS, 24 814 population male controls without any defects and 11 096
      malformed male controls with other isolated defect. Among exposures, prospective
      medically recorded chronic diseases and medically recorded or retrospective
      maternal information regarding acute diseases and drug treatments were evaluated
      in the study groups. Maternal epilepsy due to the treatment of valproate (odds
      ratio [OR] with 95% confidence interval [CI]: 1.97, 1.07-3.61) and cervical
      erosion (4.09, 1.84-9.12) were associated with a higher risk of IHS. In addition,
      there was an association of oral nystatin (1.94, 1.22-3.09), lynestrenol (26.66,
      8.69-81.80) and ethynilestradiol (3.51, 1.61-7.67) treatments in the mothers of
      cases with a higher risk for IHS. In conclusion, maternal cervical erosion,
      valproate, nystatin, lynestrenol and ethynilestradiol associated with a higher
      risk for IHS. 

PMID- 24279372
TI  - Potential of a multiparametric optical sensor for determining in situ the
      maturity components of red and white Vitis vinifera wine grapes.
AB  - A nondestructive fluorescence-based technique for evaluating Vitis vinifera L.
      grape maturity using a portable sensor (Multiplex) is presented. It provides
      indices of anthocyanins and chlorophyll in Cabernet Sauvignon, Merlot, and
      Sangiovese red grapes and of flavonols and chlorophyll in Vermentino white
      grapes. The good exponential relationship between the anthocyanin index and the
      actual anthocyanin content determined by wet chemistry was used to estimate grape
      anthocyanins from in field sensor data during ripening. Marked differences were
      found in the kinetics and the amount of anthocyanins between cultivars and
      between seasons. A sensor-driven mapping of the anthocyanin content in the
      grapes, expressed as g.kg(-1) fresh weight, was performed on a 7-ha vineyard
      planted with Sangiovese. In the Vermentino, the flavonol index was favorably
      correlated to the actual content of berry skin flavonols determined by means of
      HPLC analysis of skin extracts. It was used to make a nondestructive estimate of
      the evolution in the flavonol concentration in grape berry samplings. The
      chlorophyll index was inversely correlated in a linear manner to the total
      soluble solids ( degrees Brix): it could, therefore, be used as a new index of
      technological maturity. The fluorescence sensor (Multiplex) possesses a high
      potential for representing an important innovative tool for controlling grape
      maturity in precision viticulture. 

PMID- 24279373
TI  - Development of a novel 3D culture system for screening features of a complex
      implantable device for CNS repair.
AB  - Tubular scaffolds which incorporate a variety of micro- and nanotopographies have
      a wide application potential in tissue engineering especially for the repair of
      spinal cord injury (SCI). We aim to produce metabolically active differentiated
      tissues within such tubes, as it is crucially important to evaluate the
      biological performance of the three-dimensional (3D) scaffold and optimize the
      bioprocesses for tissue culture. Because of the complex 3D configuration and the
      presence of various topographies, it is rarely possible to observe and analyze
      cells within such scaffolds in situ. Thus, we aim to develop scaled down mini
      chambers as simplified in vitro simulation systems, to bridge the gap between two
      dimensional (2D) cell cultures on structured substrates and three-dimensional
      (3D) tissue culture. The mini-chambers were manipulated to systematically
      simulate and evaluate the influences of gravity, topography, fluid flow, and
      scaffold dimension on three exemplary cell models that play a role in CNS repair
      (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a
      tubular scaffold created by rolling up a microstructured membrane. Since we use
      CNS myelinating cultures, we can confirm that the scaffold does not affect neural
      cell differentiation. It was found that heterogeneous cell distribution within
      the tubular constructs was caused by a combination of gravity, fluid flow,
      topography, and scaffold configuration, while cell survival was influenced by
      scaffold length, porosity, and thickness. This research demonstrates that the
      mini-chambers represent a viable, novel, scale down approach for the evaluation
      of complex 3D scaffolds as well as providing a microbioprocessing strategy for
      tissue engineering and the potential repair of SCI. 

PMID- 24279374
TI  - Circulating microRNA: a novel potential biomarker for early diagnosis of
      intracranial aneurysm rupture a case control study.
AB  - OBJECTIVE: To investigate warning effect of serum miRNA for intracranial aneurysm
      rupture through microarray hybridization. METHODS: 24 were selected from 560
      patients in our department and divided into group A, B, C and D. They are
      aneurysms with daughter aneurysms group, aneurysm without daughter aneurysms
      group, ruptured aneurysms group and angiography negative group. Then a microarray
      study was carried out using serum miRNA. Differentially expressed miRNAs were
      identified. Cluster analysis was performed in order to make the results looks
      more intuitive and potential gene targets were retrieved from miRNA target
      prediction databases. RESULTS: Microarray study identified 86 miRNAs with
      significantly different (p < 0.05) expression levels between three experimental
      groups and control group. Among them 69 are up-regulated and 17 are down
      regulated. All miRNAs in group A are up-regulated, while there are up and down
      regulated in group B and C. A total of 8291 predicted target genes are related to
      these miRNAs. Bioinformatic analysis revealed that several target genes are
      involved in apoptosis and activation of cells associated with function of
      vascular wall. CONCLUSION: Our gene level approach reveals several different
      serum miRNAs between normal people and aneurysm patients, as well as among
      different phases of aneurysm, suggesting that miRNA may participate in the
      regulation of the occurrence and development of intracranial aneurysm, and also
      have warning effect for intracranial aneurysm rupture. All differently expressed
      miRNA in group A are up-regulated, which may suggesting protective function of
      miRNA for intracranial vascular wall.

PMID- 24279375
TI  - Aging is associated with highly defined epigenetic changes in the human
      epidermis.
AB  - BACKGROUND: Altered DNA methylation patterns represent an attractive mechanism
      for understanding the phenotypic changes associated with human aging. Several
      studies have described global and complex age-related methylation changes, but
      their structural and functional significance has remained largely unclear.
      RESULTS: We have used transcriptome sequencing to characterize age-related gene
      expression changes in the human epidermis. The results revealed a significant set
      of 75 differentially expressed genes with a strong functional relationship to
      skin homeostasis. We then used whole-genome bisulfite sequencing to identify age
      related methylation changes at single-base resolution. Data analysis revealed no
      global aberrations, but rather highly localized methylation changes, particularly
      in promoter and enhancer regions that were associated with altered
      transcriptional activity. CONCLUSIONS: Our results suggest that the core
      developmental program of human skin is stably maintained through the aging
      process and that aging is associated with a limited destabilization of the
      epigenome at gene regulatory elements.

PMID- 24279376
TI  - Dose-escalated salvage radiotherapy after radical prostatectomy in high risk
      prostate cancer patients without hormone therapy: outcome, prognostic factors and
      late toxicity.
AB  - PURPOSE: Evaluation of dose escalated salvage radiotherapy (SRT) in patients
      after radical prostatectomy (RP) who had never received antihormonal therapy. To
      investigate prognostic factors of the outcome of SRT and to analyze which patient
      subsets benefit most from dose escalation. MATERIALS AND METHODS: Between 2002
      and 2008, 76 patients were treated in three different dose-groups: an earlier
      cohort treated with 66 Gy irrespective of pre-RT-characteristics and two later
      cohorts treated with 70 Gy or 75 Gy depending on pre-RT-characteristics.
      Biochemical-relapse-free-survival (bRFS), clinical-relapse-free-survival (cRFS)
      and late toxicity were evaluated. RESULTS: Four-year bRFS and cRFS were 62.5% and
      85%. Gleason score <8, positive surgical resection margin (PSRM) and low PSA
      (<=0.5 ng/ml) before SRT resulted in higher bRFS. Analysis of the whole group
      showed no clear dose-outcome relationship. Patients with PSRM, however, had
      improved bRFS when escalating >66 Gy. While > 70 Gy did not improve the overall
      results, 4-year bRFS for patients with manifest local recurrence in the high-dose
      group was still comparable to those without manifest local recurrences. No grade
      4 and minimal grade 3 gastrointestinal and urinary toxicity were observed.
      CONCLUSIONS: Dose-escalated SRT achieves high biochemical control. The data
      strongly support the application of at least 70 Gy rather than 66 Gy. They do not
      prove positive effects of doses >70 Gy but do not disprove them as these doses
      were only applied to an unfavorable patients selection.

PMID- 24279378
TI  - Synthesis and optoelectronic properties of 6,12-bis(amino)anthanthrene
      derivatives.
AB  - A series of 6,12-bis(amino) anthanthrene-based conjugated molecules were prepared
      and characterized using UV-vis and fluorescence spectroscopy and cyclic
      voltammetry. The absorption spectra and redox potentials of these molecules can
      be modulated by changing the conjugated moieties linked at the 4 and 10
      positions. Moreover, the optoelectronic properties of these derivatives strongly
      depend on the moieties attached to the nitrogen atoms at the 6 and 12 positions. 

PMID- 24279377
TI  - Management of incidental and suspicious gallbladder cancer: focus on early
      referral to a tertiary centre.
AB  - OBJECTIVES: This study was conducted to assess the management of incidental
      gallbladder cancer and indeterminate gallbladder lesions. Its secondary aim
      referred to the devising of a management pathway for these patients. METHODS:
      Patients referred with incidental gallbladder cancer and indeterminate
      gallbladder lesions during 2002-2011 were identified from a prospectively
      maintained database. Collated data included operative findings, histopathological
      data and survival outcomes. RESULTS: The study included a total of 104 patients,
      40 of whom had incidental gallbladder cancer following cholecystectomy. In this
      group, the index cholecystectomy was considered curative (T-is/T1a stage) in
      three patients; 11 patients underwent further resection, and 26 patients were
      inoperable. One-, 3- and 5-year overall survival rates were 91.1%, 91.0% and
      60.7%, respectively, in patients who underwent re-resection. Of the 64 patients
      with indeterminate gallbladder lesions, 54 patients underwent modified radical
      cholecystectomy. Seven patients were found to have gallbladder cancer. One-, 3-
      and 5-year overall survival rates were 85.9%, 43.1% and 42.8%, respectively. Five
      year overall survival in patients treated with surgery for gallbladder cancer was
      59.9%. CONCLUSIONS: The majority of patients with incidental gallbladder cancer
      were not amenable to further potentially curative resection. The radiological
      suspicion of gallbladder cancer should lead to prompt referral to a tertiary
      hepatobiliary unit for further management.

PMID- 24279379
TI  - Psychological intervention with couples coping with breast cancer: a systematic
      review.
AB  - OBJECTIVE: Information about psychological intervention with couples coping with
      breast cancer is not well-disseminated. This can be explained, at least in part,
      by the absence of knowledge about the efficacy of this kind of intervention. The
      aim of the present systematic review is to identify and describe psychological
      interventions for couples coping with breast cancer and evaluate their efficacy.
      DESIGN: Studies identified by a searching multiple literature databases related
      to health and psychology between 1975 and 2013. Rigorous inclusion and exclusion
      criteria were utilised. RESULTS: Of 129 abstracts, 13 were extracted for further
      analysis and a final ten studies were deemed eligible for inclusion. Data were
      extracted from each study regarding study sample characteristics, design, results
      and methodological limitations. The results obtained were mixed in regard to
      efficacy, although the overwhelming majority of studies (eight studies) found
      benefits for both women and their partners in some dimensions, such as quality of
      life, psychological distress, relationship functioning and physical symptoms
      associated with cancer. CONCLUSION: Psychological interventions for couples
      coping with breast cancer appear to be effective for both women and their
      partners. However, further studies are needed to evaluate the efficacy of couple
      based interventions and, to identify for whom and how they are more effective.

PMID- 24279380
TI  - Enantioselective, nickel-catalyzed Suzuki cross-coupling of quinolinium ions.
AB  - Quinolinium ions are engaged in an asymmetric, Ni-catalyzed Suzuki cross-coupling
      to yield 2-aryl- and 2-heteroaryl-1,2-dihydroquinolines. Key to the development
      of this method is the use of a Ni(II) precatalyst that activates without the need
      for strong reductants or high temperatures. The Ni-iminium activation mode is
      demonstrated as an exceptionally mild pathway to generate enantioenriched
      products from racemic starting materials. 

PMID- 24279381
TI  - Low-dose tissue plasminogen activator is as effective as standard tissue
      plasminogen activator administration for the treatment of acute ischemic stroke.
AB  - We compared the efficacy of intravenous (IV) combination of low-dose tissue
      plasminogen activator (tPA) and urokinase (UK) versus either classical IV tPA or
      UK alone for acute ischemic stroke (AIS) within 4.5 h of symptom onset. One
      hundred fifty-three AIS patients were treated with 1 of 3 different IV
      thrombolytic therapies within a 4.5-h time window. Clinical data included age,
      gender, type of therapy, NIHSS score, time from onset to needle, ASPECTS, mRS at
      90 days, and medical history. The outcomes were DeltaNIHSS-a (the difference
      between NIHSS scores at admission and 24 h); DeltaNIHSS-b (difference between
      NIHSS scores at admission and 7 days), and mRS at 90 days. Multivariate logistic
      regression (MLR) was used to determine if treatments or other variables could
      predict these outcomes. Of 153 patients, 60.1% had a good outcome and 39.9% had a
      poor outcome. The most important predictors of 90-day mRS were AF history (p <
      0.001) and NIHSS score at admission (p = 0.001). Age (p = 0.004) and treatment
      type (p = 0.043) that were also significantly associated with 90-day mRS. IV tPA
      yielded the best outcome, compared to low-dose tPA/UK (OR = 1.17) and UK alone
      (OR = 1.42). Low-dose tPA/UK also resulted in better outcome than UK alone did
      (OR = 1.12). We conclude that low-dose IV tPA with UK administered within a 4.5-h
      time window was effective and likely comparable to classical IV tPA thrombolysis.

PMID- 24279382
TI  - Structure and expression profile of the sucrose synthase gene family in the
      rubber tree: indicative of roles in stress response and sucrose utilization in
      the laticifers.
AB  - Sucrose synthase (Sus, EC 2.4.1.13) is widely recognized as a key enzyme in
      sucrose metabolism in plants. However, nothing is known about this gene family in
      Hevea brasiliensis (para rubber tree). Here, we identified six Sus genes in H.
      brasiliensis that comprise the entire Sus family in this species. Analysis of the
      gene structure and phylogeny of the Sus genes demonstrates evolutionary
      conservation in the Sus families across Hevea and other plant species. The
      expression of Sus genes was investigated via Solexa sequencing and quantitative
      PCR in various tissues, at various phases of leaf development, and under abiotic
      stresses and ethylene treatment. The Sus genes exhibited distinct but partially
      redundant expression profiles. Each tissue has one abundant Sus isoform, with
      HbSus3, 4 and 5 being the predominant isoforms in latex (cytoplasm of rubber
      producing laticifers), bark and root, respectively. HbSus1 and 6 were barely
      expressed in any tissue examined. In mature leaves (source), all HbSus genes were
      expressed at low levels, but HbSus3 and 4 were abundantly expressed in immature
      leaves (sink). Low temperature and drought treatments conspicuously induced
      HbSus5 expression in root and leaf, suggesting a role in stress responses. HbSus2
      and 3 transcripts were decreased by ethylene treatment, consistent with the
      reduced sucrose-synthesizing activity of Sus enzymes in the latex in response to
      ethylene stimulation. Our results are beneficial to further determination of
      functions for the Sus genes in Hevea trees, especially roles in regulating latex
      regeneration. 

PMID- 24279383
TI  - Characterization of the Pseudomonas aeruginosa metalloendopeptidase, Mep72, a
      member of the Vfr regulon.
AB  - BACKGROUND: Pseudomonas aeruginosa Vfr (the virulence factor regulator) enhances
      P. aeruginosa virulence by positively regulating the expression of numerous
      virulence genes. A previous microarray analysis identified numerous genes
      positively regulated by Vfr in strain PAK, including the yet uncharacterized
      PA2782 and PA2783. RESULTS: In this study, we report the detailed
      characterization of PA2783 in the P. aeruginosa strain PAO1. RT-PCR analysis
      confirmed that PA2782-PA2783 constitute an operon. A mutation in vfr
      significantly reduced the expression of both genes. The predicted protein encoded
      by PA2783 contains a typical leader peptide at its amino terminus end as well as
      metalloendopeptidase and carbohydrate binding motifs at its amino terminus and
      carboxy terminus regions, respectively. An in-frame PA2783::phoA fusion encoded a
      hybrid protein that was exported to the periplasmic space of Escherichia coli and
      P. aeruginosa. In PAO1, the proteolytic activity of the PA2783-encoded protein
      was masked by other P. aeruginosa extracellular proteases but an E. coli strain
      carrying a PA2783 recombinant plasmid produced considerable proteolytic activity.
      The outer membrane fraction of an E. coli strain in which PA2783 was
      overexpressed contained specific endopeptidase activity. In the presence of cAMP,
      purified recombinant Vfr (rVfr) bound to a 98-bp fragment within the PA2782
      PA2783 upstream region that carries a putative Vfr consensus sequence. Through a
      series of electrophoretic mobility shift assays, we localized rVfr binding to a
      33-bp fragment that contains part of the Vfr consensus sequence and a 5-bp
      imperfect (3/5) inverted repeat at its 3' and 5' ends (TGGCG-N22-CGCTG). Deletion
      of either repeat eliminated Vfr binding. CONCLUSIONS: PA2782 and PA2783
      constitute an operon whose transcription is positively regulated by Vfr. The
      expression of PA2783 throughout the growth cycle of P. aeruginosa follows a
      unique pattern. PA2783 codes for a secreted metalloendopeptidase, which we named
      Mep72. Mep72, which has metalloendopeptidase and carbohydrate-binding domains,
      produced proteolytic and endopeptidase activities in E. coli. Vfr directly
      regulates the expression of the PA2782-mep72 operon by binding to its upstream
      region. However, unlike other Vfr-targeted genes, Vfr binding does not require an
      intact Vfr consensus binding sequence.

PMID- 24279384
TI  - The effects of aging on apoptosis following myocardial infarction.
AB  - BACKGROUND: Aging is associated with higher incidence of heart failure and death
      following myocardial infarction (MI). The molecular and cellular changes that
      lead to these worse outcomes are not known. METHODS AND RESULTS: Young and aging
      mice underwent induction of MI by LAD ligation. There was a significant increase
      in mortality in the aging mice. Neither the young nor aging hearts after MI had
      inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after
      MI in young and aging mice, but to a much greater degree in the aging mice.
      Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated
      caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P <
      0.05), but not in aging mice. Gene pathway profiling demonstrated activation of
      both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may
      contribute to their resistance to caspase inhibition. CONCLUSIONS: Aging hearts
      activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are
      resistant to antiapoptotic therapies following MI. Novel or combination
      approaches may be required to improve outcomes in aging patients following MI.

PMID- 24279385
TI  - Ischemic stroke and intestinal bleeding under dabigatran in metabolic myopathy.
AB  - OBJECTIVES: The subsequent occurrence of an ischemic thromboembolic event and a
      bleeding shortly after discontinuation of dabigatran has not been published. CASE
      REPORT: In an 89-year-old female with atrial fibrillation dabigatran had been
      started 11 days before admission, following a transitory ischemic attack.
      Phenprocoumon had been stopped 1 month earlier because of a hematoma after a
      fall. Although dabigatran was discontinued already on hospital day 1, she
      experienced an intestinal bleeding on hospital day three and an ischemic stroke
      on hospital day 6. As blood coagulation parameters were still abnormal on
      hospital day 2, intestinal bleeding was attributed to the prolonged
      antithrombotic effect or the interaction of dabigatran with the comedication.
      Stroke was attributed to the absence of a sufficient antithrombotic effect or a
      rebound effect 5 days after discontinuation of dabigatran. Clinical neurological
      examination additionally suggested a neuromuscular disorder. CONCLUSIONS:
      Ischemic stroke and intestinal bleeding may consecutively occur shortly after
      stopping dabigatran. Coagulation parameters may remain abnormal even 2 days after
      discontinuation of dabigatran. Dabigatran should be applied with caution in
      elderly patients with renal insufficiency who also take drugs, which enhance the
      absorption of dabigatran.

PMID- 24279386
TI  - Morphometric profile of the localised renal tumors managed either by open or
      robot-assisted nephron-sparing surgery: the impact of scoring systems on the
      decision making process.
AB  - BACKGROUND: Nephrometric scoring systems aim to improve the manner in which
      tumoral complexity is measured and reported. Each system provides a way to
      objectively measure specific tumor features that influence technical feasibility.
      In this study we aimed to determine how nephrometric scoring systems tailored our
      approach to the surgical treatment of localised renal masses. METHODS: Charts of
      the patients with localised renal tumors, who were managed by either open or
      robot-assisted nephron-sparing surgery between May 2010 and June 2012, were
      retrospectively reviewed. Nephrometric scores [radius, exophytic/endophytic,
      nearness, anterior/posterior, location (R.E.N.A.L.) score, preoperative aspects
      and dimensions used for anatomic (P.A.D.U.A.) classification and centrality index
      (C-index)] were calculated based on preoperative imaging findings. Perioperative
      data were recorded. Morphometric characteristics of the renal masses were
      compared. Additionally, the difference between surgical alternative subgroups in
      terms of morphometric variables and the predictive power of each scoring system
      in determining the details of the surgical plan were investigated. Furthermore,
      surgical preferences in different nephrometric categories were compared. RESULTS:
      Mean R.E.N.A.L. and P.A.D.U.A. scores of the tumors treated with robotic surgery
      were significantly lower than those managed by open surgery. R.E.N.A.L.
      nephrometry score showed significant differences between most of the surgical
      alternative subgroups. P.A.D.U.A. and C-index differences were significant only
      between robotic off-clamp and open clamped cases. Tumors that required open
      conversion had significantly higher mean R.E.N.A.L. and P.A.D.U.A. score. High
      R.E.N.A.L. score (cut-off: 6.5) and high P.A.D.U.A. score (cut-off: 7.5) were
      found to be significant predictors of the surgical route. Significantly more
      tumors with moderate R.E.N.A.L. score were managed through the open approach,
      while the significant majority of those with low R.E.N.A.L. and low P.A.D.U.A.
      score were operated by robotic assistance. CONCLUSIONS: R.E.N.A.L. and P.A.D.U.A.
      scores influenced our surgical treatment strategy for localized renal masses.
      High R.E.N.A.L. and P.A.D.U.A. scores increased the likelihood of an open NSS.

PMID- 24279387
TI  - Kinetics of the thermal degradation of patulin in the presence of ascorbic acid.
AB  - Degradation of the mycotoxin patulin between 25 and 85  degrees C without and
      with added ascorbic acid was studied, and the effectiveness of linear and
      nonlinear models for predicting reaction rates was compared. In agreement with
      previous reports, ascorbic acid significantly increased (P <= 0.05) the rate of
      patulin degradation at all temperatures studied. The data for patulin degradation
      in the absence of ascorbic acid were adequately modeled using a zero-order linear
      kinetic model. However, the predictive abilities of zero and higher-order linear
      models were not adequate to describe the more complex reactions that likely
      occurred when ascorbic acid was added. In contrast, the nonlinear Weibull model
      adequately described the patulin-ascorbic acid reaction throughout the
      temperature range studied. Zero-order rate constants and Weibull scale values for
      each of the respective reactions followed the Arrhenius law. Activation energies
      of 58.7 +/- 3.9 and 29.6 +/- 1.9 kJ mol-1 for the reaction without and with
      ascorbic acid, respectively, confirmed decreased patulin stability in the
      presence of ascorbic acid and suggested that the mechanisms for the 2 degradation
      reactions were different.

PMID- 24279388
TI  - Silicone oil emulsions: strategies to improve their stability and applications in
      hair care products.
AB  - Silicone oils have wide range of applications in personal care products due to
      their unique properties of high lubricity, non-toxicity, excessive spreading and
      film formation. They are usually employed in the form of emulsions due to their
      inert nature. Until now, different conventional emulsification techniques have
      been developed and applied to prepare silicone oil emulsions. The size and
      uniformity of emulsions showed important influence on stability of droplets,
      which further affect the application performance. Therefore, various strategies
      were developed to improve the stability as well as application performance of
      silicone oil emulsions. In this review, we highlight different factors
      influencing the stability of silicone oil emulsions and explain various
      strategies to overcome the stability problems. In addition, the silicone
      deposition on the surface of hair substrates and different approaches to increase
      their deposition are also discussed in detail. 

PMID- 24279389
TI  - Characterization of non-CG genomic hypomethylation associated with gamma-ray
      induced suppression of CMT3 transcription in Arabidopsis thaliana.
AB  - Ionizing radiation causes various epigenetic changes, as well as a variety of DNA
      lesions such as strand breaks, cross-links, oxidative damages, etc., in genomes.
      However, radiation-induced epigenetic changes have rarely been substantiated in
      plant genomes. The current study investigates whether DNA methylation of
      Arabidopsis thaliana genome is altered by gamma rays. We found that genomic DNA
      methylation decreased in wild-type plants with increasing doses of gamma rays (5,
      50 and 200 Gy). Irradiation with 200 Gy significantly increased the expression of
      transcriptionally inactive centromeric 180-bp (CEN) and transcriptionally silent
      information (TSI) repeats. This increase suggested that there was a substantial
      release of transcriptional gene silencing by gamma rays, probably by induction of
      DNA hypomethylation. High expression of the DNA demethylase ROS1 and low
      expression of the DNA methyltransferase CMT3 supported this hypothesis. Moreover,
      Southern blot analysis following digestion of genomic DNA with methylation
      sensitive enzymes revealed that the DNA hypomethylation occured preferentially at
      CHG or CHH sites rather than CG sites, depending on the radiation dose. Unlike
      CEN and TSI repeats, the number of Ta3, AtSN1 and FWA repeats decreased in
      transcription but increased in non-CG methylation. In addition, the cmt3-11
      mutant showed neither DNA hypomethylation nor transcriptional activation of
      silenced repeats upon gamma irradiation. Furthermore, profiles of genome-wide
      transcriptomes in response to gamma rays differed between the wild-type and cmt3
      11 mutant. These results suggest that gamma irradiation induced DNA
      hypomethylation preferentially at non-CG sites of transcriptionally inactive
      repeats in a locus-specific manner, which depends on CMT3 activity. 

PMID- 24279390
TI  - The pain and pleasure of being what one is: viewpoints of health professionals
      and patients about being overweight/obese.
AB  - The objective of this article is to discuss the meanings that health
      professionals and patients in treatment attribute to obesity. The research
      consisted of a qualitative survey in health, based on in-depth interviews with
      patients and professionals at an out-patient clinic at the University Hospital in
      Barcelona, Spain. Here, we discuss the concept of obesity, the meanings of
      diagnoses, the singularities involved in managing treatment, and the process of
      becoming ill, all in the light of the anthropology of health that has a
      sociocultural orientation. Obesity is usually seen by the professionals as a risk
      factor disease. For patients, the incorporation of this rationality is procedural
      and is mixed in with other meanings attributed to being overweight/obese that
      have been gradually developed throughout life. A patient's autonomy in choosing
      to be fat, or obese, and to adhere to treatment, is defined as a process that
      requires support in order to come to joint proposals in caring for these
      problems. 

PMID- 24279391
TI  - Electronic and chemical properties of a surface-terminated screw dislocation in
      MgO.
AB  - Dislocations represent an important and ubiquitous class of topological defect
      found at the surfaces of metal oxide materials. They are thought to influence
      processes as diverse as crystal growth, corrosion, charge trapping, luminescence,
      molecular adsorption, and catalytic activity; however, their electronic and
      chemical properties remain poorly understood. Here, through a detailed first
      principles investigation into the properties of a surface-terminated screw
      dislocation in MgO we provide atomistic insight into these issues. We show that
      surface dislocations can exhibit intriguing electron trapping properties which
      are important for understanding the chemical and electronic characteristics of
      oxide surfaces. The results presented in this article taken together with recent
      experimental reports show that surface dislocations can be equally as important
      as more commonly considered surface defects, such as steps, kinks, and vacancies,
      but are now just beginning to be understood. 

PMID- 24279392
TI  - Heteroleptic silver(I) complexes prepared from phenanthroline and bis-phosphine
      ligands.
AB  - The heteroleptic coordination scenario of silver(I) with various phenanthroline
      ligands (NN) and different bis-phosphine (PP) derivatives has been investigated.
      In addition to the X-ray crystal structural characterization of the resulting
      mixed ligand Ag(I) complexes, detailed NMR studies have been performed to
      disclose the behavior of the prepared silver(I) complexes in solution. The
      results obtained with silver(I) have been also systematically related to the one
      obtained for copper(I) with the same combination of PP and NN ligands. Starting
      from an equimolar mixture of AgBF4, bis[(2-diphenylphosphino)phenyl] ether (POP),
      and 1,10-phenanthroline (phen), the mononuclear complex [Ag(POP)(phen)](+) has
      been obtained as the tetrafluoroborate salt. By following the same experimental
      procedure starting from bis(diphenylphosphino)methane (dppm) or 1,3
      bis(diphenylphosphino)propane (dppp) as the PP ligand, dinuclear complexes with
      two bridging PP ligands, i.e., [Ag2(NN)2(MU-dppm)2](2+) and [Ag2(NN)2(MU
      dppp)2](2+) with NN = phen or Bphen (bathophenanthroline), have been isolated as
      the tetrafluoroborate salts. Surprisingly, by using an equimolar ratio of AgBF4,
      phen or Bphen, and 1,2-bis(diphenyl-phosphino)ethane (dppe), the corresponding
      monobridged diphosphine dinuclear complexes [Ag2(NN)2(MU-dppe)](2+) have been
      obtained as the tetrafluoroborate salts. These compounds have been also prepared
      in excellent yield by using a more appropriate 2:1:2 (phen:dppe:Ag)
      stoichiometry. These results prompted us to also perform the reactions with dppm
      and dppp using a 1:2:2 (PP:NN:Ag) stoichiometry. Under these conditions,
      [Ag2(NN)2(MU-dppm)](BF4)2 (NN = phen or Bphen) and [Ag2(NN)2(MU-dppp)](BF4)2 (NN
      = phen or Bphen) have been obtained upon crystallization. When compared to their
      copper(I) analogues, the complexation scenario becomes more complex with
      silver(I) as the system tolerates also coordinatively frustrated metal ligand
      assemblies, i.e., with a trigonal coordination geometry. Depending on the
      stoichiometry or on the nature of the PP partner, silver(I) shows an adaptive
      capability leading to various complexes with different coordination geometries
      and composition. However, as in the case of copper(I), their solution behavior is
      highly dependent on the relative thermodynamic stability of the various possible
      complexes. In most of the cases, a single Ag(I) complex is observed in solution
      and the NMR data are in a perfect agreement with their solid state structures.
      The dppp-containing complexes are the only notable exception; both [Ag2(NN)2(MU
      dppp)2](BF4)2 and [Ag2(NN)2(MU-dppp)](BF4)2 are stable in the solid state but a
      dynamic mixture is observed as soon as these compounds are dissolved. Finally,
      whereas both dppe and dppp are chelating ligands for copper(I), it is not the
      case anymore with silver(I) for which a destabilization of species with chelating
      dppe and dppp ligands is clearly suggested by our results. 

PMID- 24279393
TI  - Newly hired nurses' and physicians' perceptions of the comprehensive health care
      orientation process: a pilot study.
AB  - AIM: To examine newly hired nurses' and physicians' perceptions of their
      orientation process in two Finnish hospitals, and to explore correlations between
      the background variables and the four aspects of a comprehensive orientation
      process. BACKGROUND: Internationally, health care organisations are being
      challenged to recruit and retain a competent workforce. Although health care
      orientation programmes increase retention and provide safe and quality care,
      studies examining it are limited. METHOD: A cross-sectional, descriptive
      questionnaire survey of registered nurses (n = 145) and physicians (n = 37)
      working in two specialised hospital settings was conducted in 2009-2010. RESULT:
      Nurses' and physicians' perceptions regarding the orientation process ranged from
      low to moderate. The results showed that 'appointed preceptor', 'duration of
      orientation' and 'profession' correlated positively and significantly with a
      comprehensive orientation process. CONCLUSION: The orientation process needs to
      be updated constantly and refined by evaluation data. In addition, incentives and
      effective support from the hospital organisation must be considered in order to
      perform the orientation process in a more comprehensive manner. IMPLICATIONS FOR
      NURSING MANAGEMENT: The results indicate that investment is needed to improve the
      orientation process in health care. Health care managers are in a crucial
      position to support the orientation process in practice and value it as a
      retention strategy.

PMID- 24279394
TI  - Dietary exposure to selected perfluoroalkyl acids (PFAAs) in four European
      regions.
AB  - The dietary exposure to selected PFAAs was estimated in four selected European
      states (Belgium, the Czech Republic, Italy and Norway) representing Western,
      Southern, Eastern and Northern Europe. The harmonised sampling programme designed
      in the European Union project PERFOOD was targeted at identifying seven selected
      PFAAs, including perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid
      (PFOA), in food items that are most important both in terms of consumption and
      based on known high contamination patterns. The estimated average dietary
      exposure for adults (18-64 years) and children (3-9 years) is generally below or
      close to 1 ng kg-1 BW day-1 for all seven PFAAs. Considering the high consumption
      of food groups that contribute most to the exposure does not result in estimates
      exceeding 4 ng kg-1 BW day-1. Thus, based on the TDIs proposed by EFSA for PFOS
      (150 ng kg-1 BW day-1) and PFOA (1500 ng kg-1 BW day-1), no concern can be
      identified. There are distinct dietary exposure patterns from region to region as
      a result of different food consumption and contamination patterns. Foods of plant
      origin (e.g. fruit and vegetables) are most important for the dietary exposure to
      PFHxA, PFOA and PFHxS, while the consumption of foods of animal origin
      (particularly fish and seafood) mostly contributes to the dietary exposure to
      PFDA and PFUnDA. For the dietary exposure to PFNA and PFOS, food of animal and
      plant origin contributes with equal importance. In conclusion, region-to-region
      differences as well as the relative importance of food of different origin for
      each PFAA should be paid more attention in further research.

PMID- 24279395
TI  - Expression of transforming growth factor beta and fibroblast growth factor 2 in
      the lens epithelium of Morioka cataract mice.
AB  - In the Morioka cataract (MCT) mice, lens opacity appears at 6 to 8 weeks of age,
      and swollen lens fiber is electron-microscopically observed at 3 weeks after
      birth. The present study was designed to characterize the expression of
      transforming growth factor beta (TGFbeta) and fibroblast growth factor 2 (FGF2)
      in the lens epithelium of the MCT mice. Immunohistochemical analysis showed that
      the expression of TGFbeta in the lens epithelium of the MCT mice was stronger
      than that of the wild-type ddY mice at 2 and 4 weeks after birth. The expression
      of TGFbeta receptors (TGFbetaRI and TGFbetaRII) and FGF2 in the lens epithelium
      of the MCT mice was stronger than that of the wild-type ddY mice at 4 weeks and
      weaker than that of the wild-type ddY mice at 15 weeks after birth. Using real
      time polymerase chain reaction (PCR), quantitative RT-PCR analysis showed that
      expression of TGFbeta1 and TGFbeta2 mRNA in the lens of 2-week-old MCT mice was
      significantly higher compared to age-matched wild-type ddY mice. These findings
      indicate that the lens epithelium of MCT mice has increased expression of TGFbeta
      before cataract affection and that changes in the expression of FGF2 as well as
      TGFbeta may contribute to the progression of the cataract in the mice. 

PMID- 24279396
TI  - Effects of amino acid derivatives on physical, mental, and physiological
      activities.
AB  - Nutritional ergogenic aids have been in use for a long time to enhance exercise
      and sports performance. Dietary components that exhibit ergogenic activity are
      numerous and their consumption is common and popular among athletes. They often
      come under scrutiny by legal authorities for their claimed benefits and safety
      concerns. Amino acid derivatives are propagated as being effective aids to
      enhance physical and mental performance in many ways, even though studies have
      pointed out that individuals who are deficient are more likely to benefit from
      dietary supplementation of amino acid derivatives than normal humans. In this
      review, some of the most common and widely used amino acids derivatives in sports
      and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been
      discussed for their effects on exercise performance, mental activity as well as
      body strength and composition. Creatine, carnitine, HMB, and taurine are reported
      to delay the onset of fatigue, improve exercise performance, and body strength.
      HMB helps in increasing fat-free mass and reduce exercise induced muscle injury.
      Taurine has been found to reduce oxidative stress during exercise and also act as
      an antihypertensive agent. Although, studies have not been able to find any
      favorable effect of tyrosine administration on exercise performance, it has been
      proved to be very effective in fighting stress, improving mood and cognitive
      performance particularly in sleep-deprived subjects. While available data from
      published studies and findings are equivocal about the efficacy of creatine,
      tyrosine, and HMB, more comprehensive researches on carnitine and taurine are
      necessary to provide evidence for the theoretical basis of their ergogenic role
      in nutritional modification and supplementation.

PMID- 24279397
TI  - Analysis of the transcriptome of Hirschmanniella oryzae to explore potential
      survival strategies and host-nematode interactions.
AB  - The rice root nematode Hirschmanniella oryzae is the most abundant plant
      parasitic nematode in flooded rice fields and is distributed world-wide. Although
      it is economically less important than sedentary nematodes, it can cause severe
      yield reductions and economic losses in specific environmental conditions. No
      transcriptome data for this genus were available until now. We have performed 454
      sequencing on a mixed life stages population to gain an insight into nematode
      plant interactions and nematode survival strategies. The results of two assembly
      strategies were combined to reduce the redundancy of the data, generating a final
      dataset of 21 360 contigs. The data were screened for putative plant cell wall
      modifying proteins, which facilitate nematode migration through host roots. A
      beta-mannanase, previously not reported in nematodes, was detected in the
      dataset. The data were screened for putative effector proteins that may alter the
      host defence mechanism. Two enzymes, chorismate mutase and isochorismatase,
      thought to be involved in the salicyclic acid pathway, were identified.
      Experimental treatments of H. oryzae with artificial seawater showed that late
      embryogenesis abundant (LEA) proteins and SXP/RAL-2 are induced, suggesting that
      these proteins are involved in the process of anhydrobiosis. The newly generated
      data can highlight potential differences between sedentary and migratory
      nematodes, and will be useful in the further study of host-nematode interactions
      and the developmental biology of this nematode. 

PMID- 24279400
TI  - Aromatic stabilization energy and magnetic properties in fulvalenes: is there a
      connection between these two aromaticity indices?
AB  - The nucleus-independent chemical shift (NICS) and Coulombic energy of 15 j,k
      fulvalenes (j, k = 3, 5, 7, 9, 11) were investigated. It was found that in all of
      the hetero derivatives (j ? k) charge transfer between the rings occurs. It
      occurs when the one ring contains 4n + 1 and the other 4n + 3 pi electrons,
      forming two rings containing numbers of pi electrons closer to 4n + 2, and also
      when both rings contain either 4n + 3 or 4n + 1 pi electrons, forming a partially
      aromatized ring and a partially antiaromatized ring. Both types of charge
      transfer are associated with aromatic stabilization energy. The NICS values are
      consistent with the above-described partial aromatization and antiaromatization.
      A semiquantitative relationship between the aromatic stabilization energy and
      NICS is given. 

PMID- 24279399
TI  - The impact of being newly diagnosed with a bipolar disorder and the short-term
      outcome of disorder-specific management.
AB  - OBJECTIVES: The aim of the study was to determine the impact of a first-time
      diagnosis of bipolar disorder in patients previously generally managed as having
      a unipolar disorder, and to quantify the impact of disorder-specific management
      strategies for such newly diagnosed patients over the following three months.
      METHODS: A total of 157 patients receiving a diagnosis of bipolar disorder for
      the first time by a psychiatrist at a specialist depression clinic completed a
      research interview and questionnaires, with 106 (68%) also completing 12-week
      quantitative and qualitative evaluations. Assessing psychiatrists undertook
      baseline and follow-up assessments recording management changes, reactions to the
      diagnosis and global changes in functioning over time. RESULTS: The majority of
      patients had a positive response to receiving a diagnosis of bipolar disorder,
      and most implemented a number of clinician-suggested bipolar management
      strategies. Patients showed improvement on five of the six self-report measures
      over the three-month study period. Multivariate analyses quantified lamotrigine
      as making the most distinctive contribution to 'improver' status, particularly
      for the bipolar II disorder subset. CONCLUSIONS: Results are encouraging in
      identifying a generally positive acceptance of a diagnosis of bipolar disorder,
      improved outcome following the introduction of diagnostic-specific management
      components, and a distinctive contribution of lamotrigine to improved three-month
      outcome.

PMID- 24279398
TI  - Viral expression associated with gastrointestinal adenocarcinomas in TCGA high
      throughput sequencing data.
AB  - BACKGROUND: Up to 20% of cancers worldwide are thought to be associated with
      microbial pathogens, including bacteria and viruses. The widely used methods of
      viral infection detection are usually limited to a few a priori suspected viruses
      in one cancer type. To our knowledge, there have not been many broad screening
      approaches to address this problem more comprehensively. METHODS: In this study,
      we performed a comprehensive screening for viruses in nine common cancers using a
      multistep computational approach. Tumor transcriptome and genome sequencing data
      were available from The Cancer Genome Atlas (TCGA). Nine hundred fifty eight
      primary tumors in nine common cancers with poor prognosis were screened against a
      non-redundant database of virus sequences. DNA sequences from normal matched
      tissue specimens were used as controls to test whether each virus is associated
      with tumors. RESULTS: We identified human papilloma virus type 18 (HPV-18) and
      four human herpes viruses (HHV) types 4, 5, 6B, and 8, also known as EBV, CMV,
      roseola virus, and KSHV, in colon, rectal, and stomach adenocarcinomas. In total,
      59% of screened gastrointestinal adenocarcinomas (GIA) were positive for at least
      one virus: 26% for EBV, 21% for CMV, 7% for HHV-6B, and 20% for HPV-18. Over 20%
      of tumors were co-infected with multiple viruses. Two viruses (EBV and CMV) were
      statistically significantly associated with colorectal cancers when compared to
      the matched healthy tissues from the same individuals (p = 0.02 and 0.03,
      respectively). HPV-18 was not detected in DNA, and thus, no association testing
      was possible. Nevertheless, HPV-18 expression patterns suggest viral integration
      in the host genome, consistent with the potentially oncogenic nature of HPV-18 in
      colorectal adenocarcinomas. The estimated counts of viral copies were below one
      per cell for all identified viruses and approached the detection limit.
      CONCLUSIONS: Our comprehensive screening for viruses in multiple cancer types
      using next-generation sequencing data clearly demonstrates the presence of viral
      sequences in GIA. EBV, CMV, and HPV-18 are potentially causal for GIA, although
      their oncogenic role is yet to be established.

PMID- 24279401
TI  - Development of a method for the quantification of caseinate traces in Italian
      commercial white wines based on liquid chromatography-electrospray ionization-ion
      trap-mass spectrometry.
AB  - A method using the combination of size exclusion-solid phase extraction and
      ultrafiltration, followed by tryptic digestion and analysis of the protein digest
      by liquid chromatography-electrospray ionization-3D ion trap-mass spectrometry
      (LC-ESI-3D IT-MS), was developed for the detection and quantification of
      caseinate traces potentially resulting from fining processes in white wines. In
      particular, several tryptic peptides generated from the main proteins
      constituting caseinate (beta-, alphaS1-, and alphaS2-caseins) were used as
      markers of its presence in the wine matrices; among them, the beta-casein peptide
      GPFPIIV was found to be the best marker for quantification purposes. Method
      linearity and sensitivity were assessed on a series of Italian commercial white
      wines, first checked for the absence of any peptide signal attributable to
      caseins introduced during their production and subsequently spiked with
      increasing concentrations of caseinate, to provide samples for matrix-matched
      calibrations. Limits of detection ranging between 0.09 and 0.29 mg/L (S/N = 3),
      according to the wine, were achieved using a 10 mL sample volume and the MS
      signal of GPFPIIV as the response related to the caseinate concentration. Such
      levels are comparable or even lower than the one (0.25 mg/L) recently adopted as
      a threshold by European Union legislation concerning the indication of milk- and
      egg-derived fining agents on wine labels, that is, the most restrictive one among
      those currently proposed in the world. 

PMID- 24279403
TI  - The h-index, the citation rating, impact factors and the aspiring researcher.

PMID- 24279402
TI  - Unusual DNA packaging characteristics in endoreduplicated Caenorhabditis elegans
      oocytes defined by in vivo accessibility to an endogenous nuclease activity.
AB  - BACKGROUND: Germ cells in animals are highly specialized to preserve the genome.
      A distinct set of chromatin structures must be properly established in germ cells
      to maintain cell fate and genome integrity. We describe DNA-surface interactions
      in activated Caenorhabditis elegans oocytes that are revealed through the
      activity of an endogenous nuclease ('endocleavage'). RESULTS: Our analysis began
      with an unexpected observation that a majority (>50%) of DNA from ovulated but
      unfertilized C. elegans oocytes can be recovered in fragments of approximately
      500 base pairs or shorter, cleaved at regular intervals (10 to 11 nt) along the
      DNA helix. In some areas of the genome, DNA cleavage patterns in these
      endoreduplicated oocytes appear consistent from cell-to-cell, indicating coherent
      rotational positioning of the DNA in chromatin. Particularly striking in this
      analysis are arrays of sensitive sites with a periodicity of approximately 10 bp
      that persist for several hundred base pairs of genomic DNA, longer than a single
      nucleosome core. Genomic regions with a strong bias toward a 10-nt periodic
      occurrence of A(n)/T(n) (so-called PATC regions) appear to exhibit a high degree
      of rotational constraint in endocleavage phasing, with a strong tendency for the
      periodic A(n)/T(n) sites to remain on the face of the helix protected from
      nuclease digestion. CONCLUSION: The present analysis provides evidence for an
      unusual structure in C. elegans oocytes in which genomic DNA and associated
      protein structures are coherently linked.

PMID- 24279404
TI  - The impact of exercise projects to promote mental wellbeing.
AB  - BACKGROUND: There is a well-established link between physical activity and
      psychological wellbeing, but less evidence on whether it can increase comfort in
      disclosure of mental health problems and help to reduce the perceived stigma of
      mental illness. AIMS: To investigate whether exercise projects, funded by the
      time to change anti-stigma programme to reduce mental health-related stigma and
      discrimination in England, can improve (1) wellbeing, (2) participation in
      physical activity, (3) readiness to disclose mental health problems or (4)
      perceived reduction in levels of stigma and discrimination. METHODS: Participants
      of exercise projects run in routine community settings by local Mind and Rethink
      Mental Illness associations completed the Warwick-Edinburgh Mental Well-being
      Scale (WEMWBS) and questions addressing the other three outcomes at baseline and
      three month follow-up (N = 2663 baseline; N = 531 three month follow-up).
      RESULTS: There was significant improvement at three months on the WEMWBS (t(386)
      = -7.64, p = <0.001, r = 0.36); readiness to disclose (chi(2)(1) = 10.86, p =
      0.001) and participation in physical activity outside of the project (chi(2)(1) =
      12.01, p = 0.001). CONCLUSIONS: Community-based exercise projects have the
      potential to produce multifaceted positive outcomes for people with mental health
      problems; however, more methodologically robust studies are needed to adequately
      determine the effects of exercise.

PMID- 24279405
TI  - Carers of forensic mental health in-patients: what factors influence their
      satisfaction with services?
AB  - BACKGROUND: Families are the main caring resource for service users with severe
      mental health problems. There has been limited work examining the needs of carers
      of people using forensic mental health services. AIMS: This study aimed to gain
      an understanding of carers satisfaction with services in forensic mental health
      inpatient settings. METHOD: A survey design was used with 63 carers interviewed
      by telephone using a structured interview schedule. The data were analysed both
      qualitatively and quantitatively. RESULTS: Most carers were pleased with the
      service provided although some negative views were expressed with specific types
      of contact. Giving appropriate information to carers was strongly associated with
      satisfaction with the service being provided. CONCLUSIONS: Carer satisfaction
      with forensic mental health services is likely to be higher with services that
      address carers' information needs. New ways of providing this information may
      offer greater opportunities for working with carers.

PMID- 24279406
TI  - A survey of mental health professionals' knowledge, attitudes and preparedness to
      respond to domestic violence.
AB  - BACKGROUND: A high proportion of psychiatric service users experience domestic
      violence, yet most cases remain undetected by clinicians. AIMS: This study aimed
      to assess mental health professionals' knowledge, attitudes and preparedness to
      respond to domestic violence. METHOD: Information was collected on psychiatrists'
      and psychiatric nurses' knowledge, attitudes and preparedness towards the
      assessment of domestic violence, using an adapted Physician Readiness to Measure
      Intimate Partner Violence Survey. RESULTS: One hundred and thirty-one
      professionals were surveyed. Only 20 (15%) professionals routinely asked all
      service users about domestic violence and just 36 (27%) provided information to
      service users following disclosure. Most professionals (60%) felt that they
      lacked adequate knowledge of support services, and 27% felt that their workplace
      did not have adequate referral resources for domestic violence. Nurses reported
      greater readiness to assess and manage domestic violence than psychiatrists (p <
      0.001), despite psychiatrists reporting greater overall knowledge (p < 0.001).
      CONCLUSIONS: Mental health professionals need to have clear referral pathways for
      service users who experience domestic violence, and to receive training on
      enhancing their knowledge and competencies to address domestic violence.

PMID- 24279407
TI  - RESPECT and Starwards: what are they, and do they impact on safety in acute ward
      settings?

PMID- 24279412
TI  - Cardiovascular fitness and haemodynamic responses to maximal cycle ergometer
      exercise test in children 6-8 years of age.
AB  - We investigated cardiovascular fitness and haemodynamic responses to maximal
      cycle ergometer exercise test in children. The participants were a population
      sample of 425 children (204 girls, 221 boys) aged 6-8 years. Heart rate (HR) and
      systolic blood pressure (SBP) were measured from the beginning of pre-exercise
      rest to the end of recovery period. We provided reference values for peak
      workload and changes in HR and SBP during and after maximal exercise test in
      girls and boys. Girls had a lower cardiovascular fitness, indicated by peak
      workload per body weight [mean (2 s) 2.7 (0.9) vs. 3.1 (1.0) W . kg(-1), P <
      0.001] and lean mass [mean (2 s) 3.5 (0.9) vs. 3.8 (1.0) W . kg(-1), P < 0.001]
      than boys. Plateau or decline in SBP close to the end of the test was found in
      about third of children and was considered a normal SBP response. Girls had a
      slower HR decrease within 2 min after the test than boys [mean (2 s) 53 (18) vs.
      59 (22) beats . min(-1), P < 0.001]. The results are useful for physicians and
      exercise physiologists to evaluate cardiovascular fitness and haemodynamic
      responses to exercise in children and to detect children with low exercise
      tolerance or abnormal haemodynamic responses to exercise.

PMID- 24279413
TI  - Computational framework for identification of intact glycopeptides in complex
      samples.
AB  - Glycosylation is an important protein modification that involves enzymatic
      attachment of sugars to amino acid residues. Understanding the structure of these
      sugars and the effects of glycosylation are vital for developing indicators of
      disease development and progression. Although computational methods based on mass
      spectrometric data have proven to be effective in monitoring changes in the
      glycome, developing such methods for the glycoproteome are challenging, largely
      due to the inherent complexity in simultaneously studying glycan structures with
      their corresponding glycosylation sites. This paper introduces a computational
      framework for identifying intact N-linked glycopeptides, i.e. glycopeptides with
      N-linked glycans attached to their glycosylation sites, in complex proteome
      samples. Scoring algorithms are presented for tandem mass spectra of
      glycopeptides resulting from collision-induced dissociation (CID), higher-energy
      C-trap dissociation (HCD), and electron transfer dissociation (ETD) fragmentation
      modes. An empirical false-discovery rate estimation method, based on a target
      decoy search approach, is derived for assigning confidence. The power of our
      method is further enhanced when multiple data sets are pooled together to
      increase identification confidence. Using this framework, 103 highly confident N
      linked glycopeptides from 53 sites across 33 glycoproteins were identified in
      complex human serum proteome samples using conventional proteomic platforms with
      standard depletion of the 7-most abundant proteins. These results indicate that
      our method is ready to be used for characterizing site-specific protein
      glycosylation in complex samples. 

PMID- 24279414
TI  - A modified VMAT adaptive radiotherapy for nasopharyngeal cancer patients based on
      CT-CT image fusion.
AB  - BACKGROUND: To investigate the feasibility and benefits of a modified adaptive
      radiotherapy (ART) by replanning in the initial CT (iCT) with new contours from a
      repeat CT (rCT) based on CT-CT image fusion for nasopharyngeal cancer (NPC)
      patients underwent volumetric modulated arc radiotherapy (VMAT). MATERIALS AND
      METHODS: Nine NPC patients underwent VMAT treatment with a rCT at 23rd fraction
      were enrolled in this study. Dosimetric differences for replanning VMAT plans in
      the iCT and in the rCT were compared. Volumetric and dosimetric changes of gross
      tumor volume (GTV) and organs at risk (OARs) of this modified ART were also
      investigated. RESULTS: No dosimetric differences between replanning in the iCT
      and in the rCT were observed. The average volume of GTV decreased from 78.83 +/-
      38.42 cm3 in the iCT to 71.44 +/- 37.46 cm3 in the rCT, but with no significant
      difference (p = 0.42).The average volume of the left and right parotid decreased
      from 19.91 +/- 4.89 cm3 and 21.58 +/- 6.16 cm3 in the iCT to 11.80 +/- 2.79 cm3
      and 13.29 +/- 4.17 cm3 in the rCT (both p < 0.01), respectively. The volume of
      other OARs did not shrink very much. No significant differences on PTVGTV and
      PTVCTV coverage were observed for replanning with this modified ART. Compared to
      the initial plans, the average mean dose of the left and right parotid after re
      optimization were decreased by 62.5 cGy (p = 0.05) and 67.3 cGy (p = 0.02),
      respectively, and the V5 (the volume receiving 5 Gy) of the left and right
      parotids were decreased by 7.8% (p = 0.01) and 11.2% (p = 0.001), respectively.
      There was no significant difference on the dose delivered to other OARs.
      CONCLUSION: Patients with NPC undergoing VMAT have significant anatomic and
      dosimetric changes to parotids. Repeat CT as an anatomic changes reference and re
      optimization in the iCT based on CT-CT image fusion was accurate enough to
      identify the volume changes and to ensure safe dose to parotids.

PMID- 24279415
TI  - Catalytic antioxidants: regenerable tellurium analogues of vitamin E.
AB  - In an effort to improve the chain-breaking capacity of the natural antioxidants,
      an octyltelluro group was introduced next to the phenolic moiety in beta- and
      delta-tocopherol. The new vitamin E analogues quenched peroxyl radicals more
      efficiently than alpha-tocopherol and were readily regenerable by aqueous N
      acetylcysteine in a simple membrane model composed of a stirring
      chlorobenzene/water two-phase system. The novel tocopherol analogues could also
      mimic the action of the glutathione peroxidase enzymes. 

PMID- 24279416
TI  - Gene-wide tagging study of the association between KCNT1 polymorphisms and the
      susceptibility and efficacy of genetic generalized epilepsy in Chinese
      population.
AB  - AIMS: The causes of genetic generalized epilepsies (GGEs) are still uncertain
      now. Some studies found that the human potassium channel, subfamily T, member 1
      (KCNT1) is the candidate gene causing malignant migrating partial seizures of
      infancy and autosomal dominant nocturnal frontal lobe epilepsy which are all rare
      genetic generalized epilepsies. The aims of this study were going to evaluate the
      association between KCNT1 common variations and the susceptibility and drug
      resistance of genetic generalized epilepsies in Chinese population. METHODS: The
      allele-specific MALDI-TOF mass spectrometry method was used to assess 17 tagSNPs
      (tagged single-nucleotide polymorphisms) of KCNT1 in 284 healthy Chinese controls
      and 483 Chinese GGEs patients including 279 anti-epileptic drug-responsive
      patients and 204 drug-resistant patients. RESULTS: Genotype distributions of all
      the selected tagSNPs were consistent with Hardy-Weinberg equilibrium in GGEs and
      healthy controls. None of the all 17 tagSNPs alleles were found to be related
      with the susceptibility and drug resistance of genetic generalized epilepsies.
      The frequencies of haplotype 5 and haplotype 1 were significantly lower in GGEs
      than that in healthy controls (2% vs. 4%, OR = 0.47 [0.27-0.94], P = 0.03) and
      obviously higher in drug-resistant patients than that in drug-response patients
      (6% vs. 3%, OR = 2.56 [1.23-5.35], P = 0.01). However, after the correction of
      multiple comparisons with Bonferroni's method, we found that the above two
      haplotypes were not associated with the susceptibility and drug resistance in
      GGEs and healthy controls. CONCLUSION: This gene-wide tagging study revealed no
      association between KCNT1 17 common variations and susceptibility of GGEs or AEDs
      (anti-epileptic drugs) efficacy of genetic generalized epilepsies in Chinese
      population.

PMID- 24279417
TI  - Phenylcyanamide ligand control of photo-induced linkage isomerism.
AB  - The photo- and electrochemically induced linkage isomerism of six new complexes
      [Ru(bpy)2(L)(dmso-S)](+), where dmso is dimethylsulfoxide, bpy is 2,2'
      bipyridine, and L(-) is pentachloro-, 2,3,5,6-tetrachloro-, 2,4,5-trichloro-, 2,4
      dichloro-, 4-chloro-, and unsubstituted phenylcyanamide anion, were investigated.
      The quantum yields of linkage isomerism forming the metastable [Ru(bpy)2(L)(dmso
      O)](+) complexes are shown to decrease with increasing donor properties of the
      phenylcyanamide ligand, and it is suggested that the donor properties of the
      cyanamide ligand stabilize the [Ru(bpy)2(L)(dmso-S)](+) complexes in the (3)MLCT
      excited state. The cyclic voltammetry of these complexes showed two oxidation
      processes: a phenylcyanamide L(0/-) couple (an assignment supported by density
      functional theory (DFT) calculations) and a Ru(III/II) couple at more positive
      potential. Upon oxidation to Ru(III), the complexes rearranged to form Ru-O
      linkage isomers, and the scan rate dependent voltammograms permitted estimates of
      the rates of linkage isomerism. 

PMID- 24279418
TI  - Automatic detection and analysis of cell motility in phase-contrast time-lapse
      images using a combination of maximally stable extremal regions and Kalman filter
      approaches.
AB  - Phase-contrast illumination is simple and most commonly used microscopic method
      to observe nonstained living cells. Automatic cell segmentation and motion
      analysis provide tools to analyze single cell motility in large cell populations.
      However, the challenge is to find a sophisticated method that is sufficiently
      accurate to generate reliable results, robust to function under the wide range of
      illumination conditions encountered in phase-contrast microscopy, and also
      computationally light for efficient analysis of large number of cells and image
      frames. To develop better automatic tools for analysis of low magnification phase
      contrast images in time-lapse cell migration movies, we investigated the
      performance of cell segmentation method that is based on the intrinsic properties
      of maximally stable extremal regions (MSER). MSER was found to be reliable and
      effective in a wide range of experimental conditions. When compared to the
      commonly used segmentation approaches, MSER required negligible preoptimization
      steps thus dramatically reducing the computation time. To analyze cell migration
      characteristics in time-lapse movies, the MSER-based automatic cell detection was
      accompanied by a Kalman filter multiobject tracker that efficiently tracked
      individual cells even in confluent cell populations. This allowed quantitative
      cell motion analysis resulting in accurate measurements of the migration
      magnitude and direction of individual cells, as well as characteristics of
      collective migration of cell groups. Our results demonstrate that MSER
      accompanied by temporal data association is a powerful tool for accurate and
      reliable analysis of the dynamic behaviour of cells in phase-contrast image
      sequences. These techniques tolerate varying and nonoptimal imaging conditions
      and due to their relatively light computational requirements they should help to
      resolve problems in computationally demanding and often time-consuming large
      scale dynamical analysis of cultured cells. 

PMID- 24279419
TI  - Large-scale analysis of somatic hypermutations in antibodies reveals which
      structural regions, positions and amino acids are modified to improve affinity.
AB  - The principles of affinity maturation of antibodies (Abs), which underlies B cell
      mediated immunity, are still under debate. It is unclear whether the antigen (Ag)
      binding site is a preferred target for mutations, and what the role of activation
      induced deaminase (AID) hotspots is in this process. Here we report a structural
      analysis of 3495 residues that have been replaced through somatic hypermutations
      (SHMs) in 196 Abs. We show that there is no correlation between the propensity of
      an amino acid to be in AID hotspot and the probability that it is replaced during
      the SHM process. Although AID hotspots may be necessary to enable SHMs, they are
      not a major driving force in determining which residues are mutated. We
      identified Ab positions that are highly mutated and significantly affect binding.
      The effect of mutation on binding energy is a major factor in determining which
      structural regions of the Ab are mutated. There is a clear preference for
      mutations at the Ag-binding site. However, positions outside this region that
      also affect binding are often preferred targets for SHMs. As for amino acid
      preferences, a general trend during SHM is to make Ab-Ag interfaces more similar
      to protein-protein interfaces in general. In different regions of the Ab, there
      are different sets of preferences for amino acid substitution. This mapping
      improves our understanding of Ab affinity maturation and may assist in Ab
      engineering. 

PMID- 24279420
TI  - Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte
      colony stimulating factors from human macrophages: role of glycosaminoglycans in
      inflammatory pathways of chronic venous disease.
AB  - Chronic venous disease (CVeD) is a debilitating condition that affects millions
      of individuals worldwide. The condition can result in varicose veins, or advance
      to severe skin changes and venous ulceration. The fundamental basis for CVeD is
      inflammation within the venous circulation and that it is subjected to increased
      hydrostatic pressure resulting in increased ambulatory venous pressure. The
      inflammation involves leukocytes, in particular macrophages and monocytes,
      inflammatory modulators and chemokines, cytokine expression, growth factors,
      metalloproteinase (MMP) activity, and many regulatory pathways that perpetuate
      inflammation. Sulodexide (SDX) is a glycosaminoglycan with pro-fibrinolytic and
      anti-thrombotic properties. We have previously demonstrated that SDX inhibits the
      secretion of pro-zymogen MMP-9 from human leukocytes without displacing high
      molecular complexes of MMP-9. The anti-inflammatory properties of SDX on
      activated leukocytes have not been well established. We hypothesized that SDX
      will reduce the secretion of inflammatory mediators from lipopolysaccharide (LPS)
      stimulated macrophages. Therefore, we evaluated the effects of SDX on LPS
      stimulated macrophage secretion of various inflammatory and anti-inflammatory
      cytokines, chemokines, and colony stimulating factors. We used microplatebased
      multiplex immunoassays. LPS-stimulated macrophages in vitro caused a substantial
      increase of interleukins, tumor necrosis factor, interferon, chemokines and
      colony stimulating factors. The addition of SDX caused both a dose-dependent and
      dose-independent decrease in nearly all of the inflammatory cytokines, chemokines
      and colony stimulating factors. These findings suggest that SDX has a significant
      effect on the release of inflammatory mediators from macrophages, and may be
      useful in the treatment of early and advanced CVeD. 

PMID- 24279421
TI  - An innovative nano-sorbent for selective solid-phase extraction and
      spectrophotometric determination of p-amino benzoic acid in cosmetic products.
AB  - OBJECTIVE: A novel nano-sorbent was developed for selective extraction and pre
      concentration of p-amino benzoic acid (PABA) prior to determination by
      spectrophotometry. METHODS: Selective extraction of PABA from aqueous solutions
      was performed using a solid-phase extraction column packed with 200 mg of nickel
      zinc-aluminium layered double hydroxide (Ni-Zn-Al LDH) as a nano-sorbent.
      Extraction procedure is based on the adsorption of p-amino benzoate ions on the
      Ni-Zn-Al-nitrate LDH and/or their exchanging with LDH interlayer nitrate ions.
      After elution of extracted analyte by 2.5 mL of 2 mol L(-1) NaCl solution, its
      concentration was determined spectrophotometrically at lambdamax = 268 nm.
      RESULTS: The spectrophotometry method gave a linear response for PABA within the
      range of 12.5-425.0 MUg L(-1) with a correlation coefficient of 0.9994. In the
      optimum experimental conditions, the limit of detection and sorption capacity
      were 3.78 MUg L(-1) and 21.25 mg g(-1) , respectively. CONCLUSION: The presented
      method uses mild separation conditions and is a sensitive, reproducible, simple,
      low-cost and environment-friendly technique that could be used for the extraction
      and determination of PABA in various cosmetic samples.

PMID- 24279422
TI  - Dietary exposure to dioxins and dioxin-like PCBs of Hong Kong adults: results of
      the first Hong Kong Total Diet Study.
AB  - Dioxins and dioxin-like polychlorinated biphenyls (PCBs) are persistent organic
      pollutants (POPs) covered by the Stockholm Convention on POPs. To assess the
      associated health risk of the Hong Kong population, the dietary exposure of the
      Hong Kong population and various age-gender subgroups to dioxins and dioxin-like
      PCBs was estimated in the first Hong Kong Total Diet Study (TDS), where food
      samples were collected and prepared "as consumed". A total of 142 composite food
      samples, mainly foods of animal origin and their products and oily food, were
      analysed for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      and dioxin-like PCBs by the high-resolution gas chromatograph/high-resolution
      mass spectrometer (HRGC/HRMS) system. Dietary exposures were estimated by
      combining the analytical results with the food consumption data of Hong Kong
      adults. The mean and 95th percentile exposures to dioxins and dioxin-like PCBs of
      the Hong Kong population were 21.9 and 59.7 pg toxic equivalent (TEQ) kg-1 body
      weight (bw) month-1 respectively, which amounted to 31.3% and 85.2% of the
      provisional tolerable monthly intake (PTMI). The main dietary source of dioxins
      and dioxin-like PCBs was "Fish and seafood and their products" (61.9% of the
      total exposure), followed by "Meat, poultry and game and their products" (20.0%)
      and "Mixed dishes" (6.95%). The study findings suggest that the Hong Kong
      population is unlikely to experience the major undesirable health effects of
      dioxins and dioxin-like PCBs.

PMID- 24279423
TI  - Facet-selective growth on nanowires yields multi-component nanostructures and
      photonic devices.
AB  - Enhanced synthetic control of the morphology, crystal structure, and composition
      of nanostructures can drive advances in nanoscale devices. Axial and radial
      semiconductor nanowires are examples of nanostructures with one and two
      structural degrees of freedom, respectively, and their synthetically tuned and
      modulated properties have led to advances in nanotransistor, nanophotonic, and
      thermoelectric devices. Similarly, developing methods that allow for synthetic
      control of greater than two degrees of freedom could enable new opportunities for
      functional nanostructures. Here we demonstrate the first regioselective nanowire
      shell synthesis in studies of Ge and Si growth on faceted Si nanowire surfaces.
      The selectively deposited Ge is crystalline, and its facet position can be
      synthetically controlled in situ. We use this synthesis to prepare electrically
      addressable nanocavities into which solution soluble species such as Au
      nanoparticles can be incorporated. The method furnishes multicomponent
      nanostructures with unique photonic properties and presents a more sophisticated
      nanodevice platform for future applications in catalysis and photodetection. 

PMID- 24279424
TI  - Tablet formulation of an active pharmaceutical ingredient with a sticking and
      filming problem: direct compression and dry granulation evaluations.
AB  - OBJECTIVE: To develop a tablet formulation for an active pharmaceutical
      ingredient for which sticking and filming problems occurred during tablet
      punching. METHODS: Direct compression and dry granulation tableting techniques
      were evaluated using factorial experimental design. The effects of chrome-coated
      punch tips, filler types and active percent in the tablet formulation by direct
      compression were evaluated. Similarly, for dry granulation using the roller
      compaction technique, three formulation factors - roller compaction pressure,
      intragranular filler percent and filler type - were studied. Tablets prepared by
      both techniques were characterized in regard to their compressibility index,
      tablet hardness, disintegration time, friability index and stickiness-filming
      index (an arbitrary index). Ten formulations were prepared by each technique.
      Using multiple response optimizations and estimated response surface plots, the
      data were analyzed to identify optimum levels for the formulation factors.
      RESULTS: Compressibility index values for all the formulations prepared by direct
      compression exceeded 25%, unlike the blends prepared by dry granulation. Both
      tablet hardness and disintegration time for direct compression formulations were
      significantly lower than for dry granulation formulations. The friability index
      values were significantly higher for direct compression formulations than for dry
      granulation formulations. All the direct compression formulations, unlike the dry
      granulation formulations, had a high stickiness-filming index. CONCLUSION:
      Statistical analysis helped in identifying the optimum levels of formulation
      factors, as well as the method for eliminating sticking and filming. Unlike the
      direct compression technique, dry granulation yielded tablets for which sticking
      and filming were completely eliminated.

PMID- 24279425
TI  - New co-processed MCC-based excipient for fast release of low solubility drugs
      from pellets prepared by extrusion-spheronization.
AB  - In this study, a new co-processed excipient composed of microcrystalline
      cellulose (MCC), sorbitol, chitosan and Eudragit(r) E, easily obtained by wet
      massing, to increase the dissolution rate of active ingredients of low water
      solubility from pellets prepared by extrusion-spheronization is evaluated.
      Indomethacin, nifedipine, furosemide, ibuprofen, prednisolone and
      hydrochlorothiazide are used as model drugs of different solubility. All pellet
      formulations evaluated showed adequate morphological, flow and mechanical
      properties. Pellets prepared with the co-processed excipient show a higher drug
      dissolution rate than those prepared with MCC and even higher than the pure drug
      powder. The fast drug dissolution and the complete disintegration (<3 min) of the
      pellets can be explained by the great porosity of the formulations, the high
      solubility of the sorbitol, the disintegrant capacity of the chitosan and the
      distribution of the Eudragit(r) E polymer particles in-between the other
      components of the co-processed mixture. In conclusion, this new co-processed
      excipient is very suitable to increase the dissolution rate of poorly soluble
      drugs from pellets prepared by extrusion-spheronization. Moreover, the drug
      release rate can be estimated from the Ln of the drug solubility in acidic
      medium. 

PMID- 24279426
TI  - Using phage display selected antibodies to dissect microbiomes for complete de
      novo genome sequencing of low abundance microbes.
AB  - BACKGROUND: Single cell genomics has revolutionized microbial sequencing, but
      complete coverage of genomes in complex microbiomes is imperfect due to enormous
      variation in organismal abundance and amplification bias. Empirical methods that
      complement rapidly improving bioinformatic tools will improve characterization of
      microbiomes and facilitate better genome coverage for low abundance microbes.
      METHODS: We describe a new approach to sequencing individual species from
      microbiomes that combines antibody phage display against intact bacteria with
      fluorescence activated cell sorting (FACS). Single chain (scFv) antibodies are
      selected using phage display against a bacteria or microbial community, resulting
      in species-specific antibodies that can be used in FACS for relative
      quantification of an organism in a community, as well as enrichment or depletion
      prior to genome sequencing. RESULTS: We selected antibodies against Lactobacillus
      acidophilus and demonstrate a FACS-based approach for identification and
      enrichment of the organism from both laboratory-cultured and commercially derived
      bacterial mixtures. The ability to selectively enrich for L. acidophilus when it
      is present at a very low abundance (<0.2%) leads to complete (>99.8%) de novo
      genome coverage whereas the standard single-cell sequencing approach is
      incomplete (<68%). We show that specific antibodies can be selected against L.
      acidophilus when the monoculture is used as antigen as well as when a community
      of 10 closely related species is used demonstrating that in principal antibodies
      can be generated against individual organisms within microbial communities.
      CONCLUSIONS: The approach presented here demonstrates that phage-selected
      antibodies against bacteria enable identification, enrichment of rare species,
      and depletion of abundant organisms making it tractable to virtually any microbe
      or microbial community. Combining antibody specificity with FACS provides a new
      approach for characterizing and manipulating microbial communities prior to
      genome sequencing.

PMID- 24279427
TI  - Spiders (Araneae) of Churchill, Manitoba: DNA barcodes and morphology reveal high
      species diversity and new Canadian records.
AB  - BACKGROUND: Arctic ecosystems, especially those near transition zones, are
      expected to be strongly impacted by climate change. Because it is positioned on
      the ecotone between tundra and boreal forest, the Churchill area is a strategic
      locality for the analysis of shifts in faunal composition. This fact has
      motivated the effort to develop a comprehensive biodiversity inventory for the
      Churchill region by coupling DNA barcoding with morphological studies. The
      present study represents one element of this effort; it focuses on analysis of
      the spider fauna at Churchill. RESULTS: 198 species were detected among 2704
      spiders analyzed, tripling the count for the Churchill region. Estimates of
      overall diversity suggest that another 10-20 species await detection. Most
      species displayed little intraspecific sequence variation (maximum <1%) in the
      barcode region of the cytochrome c oxidase subunit I (COI) gene, but four species
      showed considerably higher values (maximum = 4.1-6.2%), suggesting cryptic
      species. All recognized species possessed a distinct haplotype array at COI with
      nearest-neighbour interspecific distances averaging 8.57%. Three species new to
      Canada were detected: Robertus lyrifer (Theridiidae), Baryphyma trifrons
      (Linyphiidae), and Satilatlas monticola (Linyphiidae). The first two species may
      represent human-mediated introductions linked to the port in Churchill, but the
      other species represents a range extension from the USA. The first description of
      the female of S. monticola was also presented. As well, one probable new species
      of Alopecosa (Lycosidae) was recognized. CONCLUSIONS: This study provides the
      first comprehensive DNA barcode reference library for the spider fauna of any
      region. Few cryptic species of spiders were detected, a result contrasting with
      the prevalence of undescribed species in several other terrestrial arthropod
      groups at Churchill. Because most (97.5%) sequence clusters at COI corresponded
      with a named taxon, DNA barcoding reliably identifies spiders in the Churchill
      fauna. The capacity of DNA barcoding to enable the identification of otherwise
      taxonomically ambiguous specimens (juveniles, females) also represents a major
      advance for future monitoring efforts on this group.

PMID- 24279429
TI  - Effects of mortality salience and perceived vulnerability on HIV testing
      intentions and behaviour.
AB  - OBJECTIVE: Research indicates that death thoughts that occur in response to
      health threats affect subsequent health behaviour. The present study examined the
      effects of mortality salience on HIV testing. DESIGN: After reading an article
      that was intended to make them perceive that they had high or low vulnerability
      to HIV, participants wrote about death or an aversive control topic. Participants
      then indicated their intentions to get tested for HIV and were given the
      opportunity to take an HIV test at the end of the study. RESULTS: Results showed
      that mortality salience increased testing behaviour among participants who were
      made to feel vulnerable to HIV, but decreased testing behaviour among
      participants who were not made to feel vulnerable to HIV infection. CONCLUSION:
      This research suggests that HIV prevention programmes must carefully consider how
      the association many people make between HIV and death may interact with people's
      perceptions of their vulnerability to HIV infection to affect their willingness
      to engage in preventative behaviours.

PMID- 24279428
TI  - Post-traumatic hypoxia is associated with prolonged cerebral cytokine production,
      higher serum biomarker levels, and poor outcome in patients with severe traumatic
      brain injury.
AB  - Secondary hypoxia is a known contributor to adverse outcomes in patients with
      traumatic brain injury (TBI). Based on the evidence that hypoxia and TBI in
      isolation induce neuroinflammation, we investigated whether TBI combined with
      hypoxia enhances cerebral cytokine production. We also explored whether increased
      concentrations of injury biomarkers discriminate between hypoxic (Hx) and
      normoxic (Nx) patients, correlate to worse outcome, and depend on blood-brain
      barrier (BBB) dysfunction. Forty-two TBI patients with Glasgow Coma Scale <=8
      were recruited. Cerebrospinal fluid (CSF) and serum were collected over 6 days.
      Patients were divided into Hx (n=22) and Nx (n=20) groups. Eight cytokines were
      measured in the CSF; albumin, S100, myelin basic protein (MBP) and neuronal
      specific enolase (NSE) were quantified in serum. CSF/serum albumin quotient was
      calculated for BBB function. Glasgow Outcome Scale Extended (GOSE) was assessed
      at 6 months post-TBI. Production of granulocye macrophage-colony stimulating
      factor (GM-CSF) was higher, and profiles of GM-CSF, interferon (IFN)-gamma and,
      to a lesser extent, tumor necrosis factor (TNF), were prolonged in the CSF of Hx
      but not Nx patients at 4-5 days post-TBI. Interleukin (IL)-2, IL-4, IL-6, and IL
      10 increased similarly in both Hx and Nx groups. S100, MBP, and NSE were
      significantly higher in Hx patients with unfavorable outcome. Among these three
      biomarkers, S100 showed the strongest correlations to GOSE after TBI-Hx. Elevated
      CSF/serum albumin quotients lasted for 5 days post-TBI and displayed similar
      profiles in Hx and Nx patients. We demonstrate for the first time that post-TBI
      hypoxia is associated with prolonged neuroinflammation, amplified extravasation
      of biomarkers, and poor outcome. S100 and MBP could be implemented to track the
      occurrence of post-TBI hypoxia, and prompt adequate treatment.

PMID- 24279431
TI  - Selection criteria for water disinfection techniques in agricultural practices.
AB  - This paper comprises a selection tool for water disinfection methods for fresh
      produce pre- and postharvest practices. A variety of water disinfection
      technologies is available on the market and no single technology is the best
      choice for all applications. It can be difficult for end users to choose the
      technology that is best fit for a specific application. Therefore, the different
      technologies were characterized in order to identify criteria that influence the
      suitability of a technology for pre- or postharvest applications. Introduced
      criteria were divided into three principal components: (i) criteria related to
      the technology and which relate to the disinfection efficiency, (ii) attention
      points for the management and proper operation, and (iii) necessities in order to
      sustain the operation with respect to the environment. The selection criteria may
      help the end user of the water disinfection technology to obtain a systematic
      insight into all relevant aspects to be considered for preliminary decision
      making on which technologies should be put to feasibility testing for water
      disinfection in pre- and postharvest practices of the fresh produce chain. 

PMID- 24279430
TI  - Hrs- and CD63-dependent competing mechanisms make different sized endosomal
      intraluminal vesicles.
AB  - Multivesicular endosomes/bodies (MVBs) contain intraluminal vesicles (ILVs) that
      bud away from the cytoplasm. Multiple mechanisms of ILV formation have been
      identified, but the relationship between different populations of ILVs and MVBs
      remains unclear. Here, we show in HeLa cells that different ILV subpopulations
      can be distinguished by size. EGF stimulation promotes the formation of large
      ESCRT-dependent ILVs, whereas depletion of the ESCRT-0 component, Hrs, promotes
      the formation of a uniformly sized population of small ILVs, the formation of
      which requires CD63. CD63 has previously been implicated in ESCRT-independent
      sorting of PMEL in MVBs and transfected PMEL is present on the small ILVs that
      form on Hrs depletion. Upregulation of CD63-dependent ILV formation by Hrs
      depletion indicates that Hrs and CD63 regulate competing machineries required for
      the generation of distinct ILV subpopulations. Taken together our results
      indicate that ILV size is influenced by their cargo and mechanism of formation
      and suggest a competitive relationship between ESCRT-dependent and -independent
      mechanisms of ILV formation within single MVBs.

PMID- 24279432
TI  - Synthesis of enantiopure 2-C-glycosyl-3-nitrochromenes.
AB  - A novel methodology has been developed to obtain enantiopure 2-C-glycosyl-3
      nitrochromenes. First, (Z)-1-bromo-1-nitroalkenes were prepared from the
      corresponding sugar aldehydes through a sodium iodide-catalyzed Henry reaction
      with bromonitromethane followed by elimination of the resulting 1-bromo-1
      nitroalkan-2-ols. In the next step, reaction of the sugar-derived (Z)-1-bromo-1
      nitroalkenes with o-hydroxybenzaldehydes afforded enantiopure (2S,3S,4S)-3-bromo
      3,4-dihydro-4-hydroxy-3-nitro-2H-1-benzopyrans, which, upon SmI2-promoted beta
      elimination, yielded chiral enantiopure 2-C-glycosyl-3-nitrochromenes. 

PMID- 24279434
TI  - Involvement of inflammasome activation in lipopolysaccharide-induced mice
      depressive-like behaviors.
AB  - AIMS: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate
      immune system that regulates the cleavage of interleukin-1beta and interleukin-18
      precursors. It can detect a wide range of danger signals and trigger a series of
      immune-inflammatory reactions. There were plenty of studies indicating that
      activation of the immune system played pivotal roles in depression. However, the
      underlying mechanisms of immune-depression interactions remained elusive and
      there was no report about the involvement of inflammasome activation in
      depression. METHODS: We established an acute depression mouse model with
      lipopolysaccharide to explore the involvement of inflammasome activation in
      depression. RESULTS: The lipopolysaccharide-treated mice displayed depressive
      like behaviors and pro-inflammatory cytokine interleukin-1beta protein and mRNA
      levels significantly increased. The NLRP3 inflammasome mRNA expression level also
      significantly elevated in depressed mice brain. Pretreatment with the NLRP3
      inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like
      behaviors induced by lipopolysaccharide. CONCLUSION: These data suggest for the
      first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced
      mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator
      between immune activation and depression, which raises the possibility that it
      may be a more specific target for the depression treatments in the near future.

PMID- 24279435
TI  - Non-dermatophyte mould onychomycosis: a clinical and epidemiological study at a
      dermatology referral centre in Bogota, Colombia.
AB  - Worldwide prevalence of non-dermatophyte mould onychomycosis has increased in
      recent years; however, available information on the topic is confusing and
      oftentimes contradictory, probably due to the small number of reported cases. The
      aim of this study was to determine and describe the aetiological agents, as well
      as the epidemiological and clinical characteristics of non-dermatophyte mould
      onychomycosis in a dermatology referral centre in Bogota, Colombia. A cross
      sectional descriptive study was conducted between January 2001 and December 2011
      among patients who attend the National Institute of Dermatology with a confirmed
      diagnosis of onychomycosis by non-dermatophytes moulds. There were 317 confirmed
      cases of non-dermatophyte mould onychomycosis in 196 women and 121 men whose
      average age was 43 years. Twenty-seven per cent of them had a history of systemic
      disease. The habit of walking and showering barefoot was the major infection
      related factor. Distal and lateral subungual presentation was the most common
      pattern of clinical presentation. The most frequent non-dermatophyte mould was
      Neoscytalidium dimidiatum followed by Fusarium spp. No relationship was observed
      with predisposing factors previously reported in the literature. Clinical
      features found in this population are indistinguishable from onychomycosis caused
      by dermatophytes. High prevalence of N. dimidiatum found here was in contrast to
      a large number of studies where other types of moulds predominate. 

PMID- 24279436
TI  - Salivary and plasma cortisol and testosterone responses to interval and tempo
      runs and a bodyweight-only circuit session in endurance-trained men.
AB  - The aim of this study was to examine the acute response to plasma and salivary
      cortisol and testosterone to three training protocols. Ten trained endurance
      athletes participated in three experimental trials, such as interval training
      (INT), tempo run (TEMP) and bodyweight-only circuit training (CIR), on separate
      days. Blood and saliva samples were collected pre- and 0, 15, 30 and 60 min post
      exercise. Peak post-exercise salivary cortisol was higher than pre-exercise in
      all trials (P < 0.01). After INT, salivary cortisol remained elevated above pre
      exercise than 60 min post-exercise. Salivary testosterone also increased post
      exercise in all trials (P < 0.05). Plasma and salivary cortisol were correlated
      between individuals (r = 0.81, 0.73-0.88) and within individuals (r = 0.81, 0.73
      0.87) (P < 0.01). Plasma and salivary testosterone was also correlated between (r
      = 0.57, 0.43-0.69) and within individuals (r = 0.60, 0.45-0.72), (P < 0.01). Peak
      cortisol and testosterone levels occurred simultaneously in plasma and saliva,
      but timing of post-exercise hormone peaks differed between trials and
      individuals. Further investigation is required to identify the mechanisms
      eliciting an increase in hormones in response to CIR. Furthermore, saliva is a
      valid alternative sampling technique for measurement of cortisol, although the
      complex, individual and situation dependent nature of the hormone response to
      acute exercise should be considered.

PMID- 24279437
TI  - On the protein folding problem in 2D-triangular lattices.
AB  - : In this paper, we present a novel approximation algorithm to solve the protein
      folding problem in HP model. Our algorithm is polynomial in terms of the length
      of the given HP string. The expected approximation ratio of our algorithm is 1
      2lognn-1 for n >= 6, where n2 is the total number of H's in a given HP string.
      The expected approximation ratio tends to reach 1 for large values of n. Hence
      our algorithm is expected to perform very well for larger HP strings. 

PMID- 24279438
TI  - [Prevalence of diabetic retinopathy and distal symmetrical diabetic
      polyneuropathy, and glomerular filtration screening upon the diagnosis of type 2
      diabetes mellitus - a cohort study].
AB  - The prospective cohort study analyzes the prevalence of microvascular
      complications at the time of dia-gnosis type 2 diabetes (DM 2). We were
      monitoring 200 outpatients (117 men and 83 women, aged from 30 to 92 years) with
      newly diagnosed and previously untreated type 2 diabetes mellitus during the
      period of August 2007 -  August 2011 accidentally sending GP or internists.
      Prevalence of diabetic retinopathy in men was 0.85% and in women 1.2%. The
      prevalence of diabetic distal symetric polyneuropathy in men was 53% and in women
      62%. The median of glomerular filtration based on a simplified MDRD 4 equation
      (according to the study Modification of Diet in Renal Disease) was 1.27 +/- 0.6
      ml/ s/ 1.73 m2 for men and 1.05 +/- 0.32 ml/ s/ 1.73 m2 for women. At baseline,
      16.6% of men and 46.2% of women enrolled in our cohort study had glomerular
      filtration rate < 1 ml/ s/ 1.73 m2.

PMID- 24279439
TI  - [Serious sepsis treatment in intensive care departments in the Czech Republic - 
      EPOSS Project pilot results].
AB  - INTRODUCTION: Severe sepsis is still associated with significant morbidity and
      mortality, which is however different, as well as its management, depending on
      the region. What is the situation in the Czech Republic and what is the character
      of patients with severe sepsis is currently not known. The aim of the project is
      to describe the processes of care, outcome and characteristics of patients with
      severe sepsis admitted to the intensive care department of the Czech Republic.
      METHODS: This is a multicentre and observational project with retrospective
      enrollment of patients who meet the criteria for severe sepsis before or within
      24 hours after admission to selected intensive care units (ICU EPOSS). RESULTS:
      394 patients were analyzed. Median age at admission was 66 (56- 76) years, males
      predominated (58.9%) and the median APACHE II score on admission was 25 (19- 32).
      Patients were predominantly medical (56.9%) and most were secondary admitted from
      other ICU (53.6%). Meeting the criteria of severe sepsis was most frequently
      within the period (+/- 4 hours) of admission the EPOSS ICU (77.6%). Median total
      fluid intake during the first 24 hours was 6,680 (4,840- 9,450) ml. Most patients
      required mechanical ventilation (58.4%). Compliance with the resuscitation bundle
      of severe sepsis in our group was very good and was associated with lower
      mortality of patients. Most frequently, the EPOSS ICU length of stay (LOS) was 7
      (3- 15) days and median hospital LOS was 13 (8- 28) days. Hospital mortality in
      our cohort was 35.8%. CONCLUSION: Introducing the project, which in its first
      stage obtained valuable and internationally comparable data about patients with
      severe sepsis admitted to the involved ICU in the Czech Republic.

PMID- 24279440
TI  - [The new blood test bio-marker SEPT9 and colorectal carcinoma screening].
AB  - Due to its high incidence and mortality rates, the colorectal carcinoma
      represents a crucial medical issue. However, when it is detected in early stage
      there is high rate of successful treatment. Thats why, early stage cancer
      screening programmes were introduced into the clinical practice. They focus on
      the finding of hidden bleeding, using various laboratory techniques,
      sigmoidoscopy, and, primarily, colonoscopy. However, screening programmes have
      not yet reached the effect required. New techniques are therefore being
      developed, such as the detection of blood bio-markers. This group includes also
      methylated SEPT9 (mSEPT9) detection in blood. We applied this test on 57
      patients; we divided the group into two parts. There were 33 asymptomatic
      individuals in the first group. In this group, we were got only one positive
      mSEPT9 result. The consequent colonoscopies were negative. The other group had 24
      proven carcinomas. Of them, two had negative mSEPT9 results. The remaining in all
      22 patients was tested mSEPT9 positive. After its efficiency is tested by further
      studies, this test may be used especially for patients with low compliance, as it
      only requires routine blood drawing.

PMID- 24279441
TI  - [Possibilities of genetic diagnostics of intestine tumour and inflammatory
      diseases in Slovakia].
AB  - In recent years, gastroenterologists focused their interest on finding the
      genetic background of inflammatory bowel disease and colon cancer. NOD2/ CARD15
      gene is still the most investigated gene of all known genes and its mutations can
      explain approximately 20% of genetic predisposition to Crohns disease. From later
      identified genes that play an important role in the etiology of Crohns disease,
      the IL23R and ATG16L1 genes have a perspective place. In the case of hereditary
      colorectal cancer, we can select by the help of genetic diagnostics, the group of
      patients with high risk of colon cancer, which requires more intensive
      monitoring. The aim is to find out the colon cancer in the early, treatable
      stage. In practical terms, genetic diagnostics of inflammatory bowel disease and
      colon cancer has no screening and only poor prognostic importance. It is
      pleasant, that the Slovak genetic workplaces are interested in this issue and in
      accordance with modern trends they try to expand its diapason.

PMID- 24279442
TI  - [Inflammatory response and C -reactive protein value in patient with acute
      coronary syndrome].
AB  - Inflammation plays an important role in the pathophysiology of acute coronary
      syndrome as well as in the process of atherosclerosis in general. At the moment
      of myocardial ischaemia, local and systemic inflammatory reaction is amplified;
      in ischaemic myocardium there is increased expression of proinflammatory
      cytokines, particularly interleukin-6, which mediates C reactive protein (CRP)
      production by hepatocytes. CRP activates the complement cascade and thereby
      contributes to the lysis and removal of damaged cardiomyocytes. Whereas in a
      healthy population CRP levels range from 1.2 to 2.0 mg / l, in patients with ACS
      the levels of CRP significantly increase with the peak of 2nd to 4th day from the
      onset of myocardial infarction. Peak CRP levels ranged from 20 to 250 mg / l in
      patients with STEMI treated conservatively, the median of peak of CRP levels was
      79 mg/ l in patients with anterior wall STEMI treated with primary PCI. There is
      a recommendation of CRP evaluation within the early risk stratification of
      patients with ACS according to the current ESC guidelines. In patients with
      NSTEMI, CRP levels > 10 mg/ l are associated with increased longterm mortality.
      In patients with STEMI treated with primary PCI, CRP levels > 79 mg/ l could
      predict negative left ventricle remodelation. The predictive value of GRACE risk
      score was improved using CRP, levels > 22 mg/ l predicted worse prognosis in
      patients with either STEMI or NSTEMI treated invasively. However, if also cardiac
      troponin and natriuretic peptides in addition to GRACE risk score were used, CRP
      levels were useless in further risk stratification improvement. In clinical
      practice, in terms of coinciding infection, problems with CRP levels
      interpretation can occur as well. Several patients either in cardiogenic shock or
      after cardiopulmonary resuscitation have signs of systemic inflammatory response,
      and sometimes it is very difficult to decide whether there is a necessity to
      iniciate the antibio-tic therapy because of infectious cause. In patients after
      cardiopulmonary resuscitation, CRP levels > 180 mg/ l indicate highly probable
      infection, but with the poor sensitivity. For patients in cardiogenic shock,
      procalcitonin appears to be more useful for the detection of infection; in this
      group of patients, procalcitonin levels > 2 ng/ ml are common, and levels > 10
      ng/ ml indicate infection undoubtedly.

PMID- 24279443
TI  - [Thyrostatic treatment and its adverse effects].
AB  - Antithyroid drugs are relatively simple molecules known as thionamides, which
      contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure.
      Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one)
      and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid
      drugs used in the United States. Methimazole is used in most of Europe and Asia,
      and carbimazole -  methimazole analogue, is used in the United Kingdom and parts
      of the former British Commonwealth. Their primary effect is to inhibit thyroid
      hormone synthesis by interfering with thyroid peroxidase mediated iodination of
      tyrosine residues in thyroglobulin and is an important step in the synthesis of
      thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or
      carbimazole), can block the conversion of thyroxine to triiodothyronine within
      the thyroid and in peripheral tissues. Antithyroid drugs may have clinically
      important immunosuppressive effects. Side effects of thionamides are usually
      mild, serious untoward effects are observed in < 5% of cases, more frequently
      during the initial phases of treatment, when the drug daily dose is higher.

PMID- 24279444
TI  - [Role of cardiac bio-markers in monitoring of cardiotoxicity after hematopoietic
      stem cell transplantation].
AB  - Advances in hematopoietic stem cell transplantation (HSCT) have increased
      survival in hematologic diseases. However, HSCT survivors are at risk of
      developing acute and longterm complications. Cardiac events, such as heart
      failure, myocardial ischemia and arrhythmias may represent potentially life 
      threatening conditions. Acute cardiotoxicity can occur during the first 100 days
      after HSCT. Conditioning regimens, including total body irradiation and high dose
      chemotherapy, previous chemoradiotherapy, including anthracyclines and chest
      irradiation, are known to be associated with an increased risk of cardiac
      complications after HSCT. Infectious complications resulting in sepsis due to
      posttransplant granulocytopenia may also impair myocardial function. Therefore
      the main strategy for minimizing cardiotoxicity is early detection of high risk
      patients and prompt prophylactic treatment. Measurement of cardio specific bio
      markers can be a valid diagnostic tool for early identification, assessment, and
      monitoring of cardiotoxicity. In the present article, we review the usefulness of
      cardiac troponins and natriuretic peptides, the most commonly used bio-markers of
      myocardial ischemia and ventricular dysfunction, to detect and to predict the
      development of cardiotoxicity after HSCT.

PMID- 24279445
TI  - [SAVOR TIMI 53 -  Saxagliptin and cardiovascular outcomes in patients with type 2
      diabetes mellitus].
AB  - BACKGROUND: The type 2 Diabetes Mellitus treatment is currently effective but
      still not ideal. A therapy based on the incretins, which represents a significant
      qualitative progress, is close to an ideal. The first completed mortality study
      with dipeptidyl peptidase (DPP 4) inhibitors is the study called SAVOR as
      presented in Amsterdam during the European Cardiology Congress in 2013.
      METHODOLOGY: SAVOR (Saxagliptin and Cardiovascular Outcomes in Patients with Type
      2 Diabetes Mellitus) randomised 16,492 patients with Type 2 Diabetes Mellitus and
      a high-risk of cardiovascular events treated with current per oral antidiabetics
      and patients treated with saxagliptin or placebo. Eight thousand eight hundred
      and twenty patients were randomised to be treated with saxagliptin and 8,212 were
      randomised to be treated with placebo. The average monitored period was 2.1
      years. RESULTS: The primary goal (cardiovascular death, nonfatal myocardial
      infarction and nonfatal CMP) occurred in 7.3% (613) patients treated with
      saxagliptin and in 7.2% (609) patients treated with placebo (HR 1.00, p < 0.001
      for non inferiority). The main secondary goal (cardiovascular death, myocardial
      infarction, vascular stroke, hospitalisation for a heart failure or angina
      pectoris and myocardial revascularisation) occurred in 12.8% (1,059) patients
      treated with saxagliptin and in 12.4% (1,034) patients treated with placebo. The
      number of hospitalisations for heart failure was 289 (3.5%) in the group treated
      with saxagliptin and 228 (2.8%) in the group treated with placebo (p = 0.007).
      CONCLUSION: DPP 4 inhibitor saxagliptin did not increase the occurrence of
      ischemic cardiovascular events but it inclined to an increased hospitalisation
      for heart failure in patients with the already present heart failure. It did not
      increase the occurrence of pancreatitis. Simultaneously it significantly improved
      the Diabetes Mellitus control, which could signal a future improvement in
      cardiovascular goals.

PMID- 24279446
TI  - [Management of superficialis thrombophlebitis. Guidelines of the Angiologiy
      Section of the Slovak Medical Chamber (2013)].
AB  - The aim of Guidelines of the Angiology Section of the Slovak Medical Chamber (AS
      SMC) is to address a last european guidelines for the management of
      thrombophlebitis superficialis, as well as results in evidence based  medicine
      (EBM) in order to assess their contribution to our expanding knowledge on
      rational management of thrombophlebitis superficialis. DISCUSSION: Superficial
      thrombophlebitis is a common disease, usually considered to be benign. However,
      the practice of systemic duplex ultrasonography has revealed a large number of
      cases of deep vein thrombosis concomitant with superficial thrombophlebitis.
      Assessment of clinical probability of deep vein thrombosis and venous
      tromboembolism and systematic duplex ultrasound investigation has been proposed
      in the initial management of superficial thrombophlebitis, to detect the presence
      of any underlying deep vein thrombosis. In contrast with extensive information on
      the management of deep vein thrombosis, there is little knowledge about the most
      appropriate treatment of the superficial thrombophlebitis. CONCLUSION: The
      treatment of superficial thrombophlebitis should improve local symptoms while
      preventing the development of complications such as venous thromboembolism. The
      most effective therapeutic approach to superficial thrombophlebitis seems to be
      represented by fondaparinux (a synthetic selective indirect inhibitor of factor
      Xa) which have been shown to prevent VTE events and the extension and/ or
      recurrence of superficial thrombophlebitis.

PMID- 24279447
TI  - [The value of ECG assessment in pulmonary embolism diagnostics].
AB  - Acute pulmonary embolism is one of the most frequent and risky cardiovascular
      diseases. Despite accessability of different examinig methods and rich clinical
      experience, pulmonary embolism is demanding disease especially in diagnostics.
      The reason might be in clinical picture, that is not typical everytime and leads
      to incorrect choice of diagnostic methods, that delay the disease assessment.
      Regarding this, precise evaluation of every each symptom and basal, resp.
      supplemental examinations is important step to rapid and right assessment of this
      diagnose.

PMID- 24279448
TI  - [Atypical fracture of metatarsal bone in a patient with multiple myeloma who was
      treated long-term with bisphosphonates].
AB  - The first reports found in professional literature on the use of bisphosphonates
      as a treatment date back to 1972. We found the first report on the use of a
      bisphosphonate comprising nitrogen in its molecule in a publication from 1990.
      Some of the adverse effects of the particular types of bisphosphonates were
      described in the registration studies. At least two serious adverse effects of
      this group of medicines had not been described until 2000. We found the first
      description of jaw osteonecrosis in relation to the longterm application of
      bisphosphonates in a publication from 2002 and we found the first description of
      an atypical bone fracture originating without a corresponding traumatic event in
      a location with no presence of an osteolytic focus in an article from 2006. These
      so  called atypical fractures, which are also called fractures without a
      corresponding traumatic event (low energy fractures), have been described to have
      occurred in femurs, in the pelvis and less frequently in the metatarsal area.
      "Atypical fractures" are linked to longterm administration of bisphosphonates,
      which significantly increases the bone density and impedes osteolysis but it
      simultaneously increases the fragility of bones and decreases their flexibility.
      The definition of an atypical fracture of the skeleton emphasises the fact that
      such fractures occur with an inadequately minimal force (energy) in the
      aforementioned predilection locations. In the following text we are describing a
      patient who has been treated for a multiple myeloma with an atypical fracture of
      the Metatarsal bone 2. This fracture occurred during a regular walk without any
      excessive load and the patient could not recall any corresponding injury or
      longer walking. The patient had been administered bisphosphonates for 34 months
      before the atypical metatarsal fracture occurred. The metatarsal bone fracture
      was treated through a nonweight  bearing regime for the sole and the pain
      diminished within a single month. In comparison with the published data of
      atypical fractures, our case concerns a short interval between initiation of the
      bisphosphonate administration and the occurrence of the atypical fracture. In the
      available literature these fractures are described after more than a five year
      application of a bisphosphonate. New pain in the bearing skeleton in patients
      treated with bisphosphonates are therefore always subject to an imaging
      examination among others to exclude an atypical fracture due to an increased
      fragility of the bone.

PMID- 24279449
TI  - Identical sets of methylated and nonmethylated genes in Ciona intestinalis sperm
      and muscle cells.
AB  - BACKGROUND: The discovery of gene body methylation, which refers to DNA
      methylation within gene coding region, suggests an as yet unknown role of DNA
      methylation at actively transcribed genes. In invertebrates, gene bodies are the
      primary targets of DNA methylation, and only a subset of expressed genes is
      modified. RESULTS: Here we investigate the tissue variability of both the global
      levels and distribution of 5-methylcytosine (5mC) in the sea squirt Ciona
      intestinalis. We find that global 5mC content of early developmental embryos is
      high, but is strikingly reduced in body wall tissues. We chose sperm and adult
      muscle cells, with high and reduced levels of global 5mC respectively, for genome
      wide analysis of 5mC targets. By means of CXXC-affinity purification followed by
      deep sequencing (CAP-seq), and genome-wide bisulfite sequencing (BS-seq), we
      designated body-methylated and unmethylated genes in each tissue. Surprisingly,
      body-methylated and unmethylated gene groups are identical in the sperm and
      muscle cells. Our analysis of microarray expression data shows that gene body
      methylation is associated with broad expression throughout development. Moreover,
      transgenic analysis reveals contrasting gene body methylation at an identical
      gene-promoter combination when integrated at different genomic sites.
      CONCLUSIONS: We conclude that gene body methylation is not a direct regulator of
      tissue specific gene expression in C. intestinalis. Our findings reveal constant
      targeting of gene body methylation irrespective of cell type, and they emphasize
      a correlation between gene body methylation and ubiquitously expressed genes. Our
      transgenic experiments suggest that the promoter does not determine the
      methylation status of the associated gene body.

PMID- 24279450
TI  - Temperature effects on the fidelity of a thermostable HIV-1 reverse
      transcriptase.
AB  - Transcriptomics and gene expression analysis are largely dependent of the
      availability of efficient thermostable reverse transcriptases (RTs). However, the
      intrinsic fidelity of DNA synthesis catalyzed by retroviral RTs is low. Reported
      error rates are in the range 1.2 * 10(-5)-6.7 * 10(-4), with oncoretroviral RTs
      being the most faithful enzymes. Wild-type HIV-1 group O (HIV-1O) RT is a
      thermostable polymerase that is able to synthesize cDNA at temperatures as high
      as 70  degrees C. At 37  degrees C, its error rate has been estimated at 5.8 *
      10(-5) in M13mp2 lacZ-based forward mutation assays. However, at higher
      temperatures (e.g. 50 and 55  degrees C), the accuracy of HIV-1O RT is increased
      by approximately two- to five-fold. At 55  degrees C, the HIV-1O RT error rate
      (1.3 * 10(-5)) was similar to that shown by the AffinityScript (Agilent
      Technologies Inc., La Jolla, CA, USA) RT, a commercially available thermostable
      murine leukaemia virus RT. At higher temperatures, the increased accuracy of the
      HIV-1 enzyme results from a lower base substitution error rate, although it shows
      a higher tendency to introduce frameshifts. Kinetic studies carried out with
      model template-primers suggest minor differences in nucleotide discrimination,
      although, at higher temperatures, HIV-1O RT showed a reduced ability to extend
      mispaired template-primers.

PMID- 24279451
TI  - Large current difference in Au-coated vertical silicon nanowire electrode array
      with functionalization of peptides.
AB  - Au-coated vertical silicon nanowire electrode array (VSNEA) was fabricated using
      a combination of bottom-up and top-down approaches by chemical vapor deposition
      and complementary metal-oxide-semiconductor process for biomolecule sensing. To
      verify the feasibility for the detection of biomolecules, Au-coated VSNEA was
      functionalized using peptides having a fluorescent probe. Cyclic voltammograms of
      the peptide-functionalized Au-coated VSNEA show a steady-state electrochemical
      current behavior. Because of the critically small dimension and vertically
      aligned nature of VSNEA, the current density of Au-coated VSNEA was dramatically
      higher than that of Au film electrodes. Au-coated VSNEA further showed a large
      current difference with and without peptides that was nine times more than that
      of Au film electrodes. These results indicate that Au-coated VSENA is highly
      effective device to detect peptides compared to conventional thin-film
      electrodes. Au-coated VSNEA can also be used as a divergent biosensor platform in
      many applications. 

PMID- 24279452
TI  - Insights on hydrogen-bond lifetimes in liquid and supercooled water.
AB  - We study the temperature dependence of the lifetime of geometric and
      geometric/energetic water hydrogen-bonds (H-bonds), down to supercooled water,
      through molecular dynamics. The probability and lifetime of H-bonds that break
      either by translational or librational motions and those of energetic broken H
      bonds, along with the effects of transient broken H-bonds and transient H-bonds,
      are considered. We show that the fraction of transiently broken energetic H-bonds
      increases at low temperatures and that this energetic breakdown is caused by
      oxygen-oxygen electrostatic repulsions upon too small amplitude librations to
      disrupt geometric H-bonds. Hence, differences between geometric and energetic
      continuous H-bond lifetimes are associated with large H-bond energy fluctuations,
      in opposition to moderate geometric fluctuations, within common energetic and
      geometric H-bond definition thresholds. Exclusion of transient broken H-bonds and
      transient H-bonds leads to H-bond definition-independent mean lifetimes and
      activation energies, ~11 kJ/mol, consistent with the reactive flux method and
      experimental scattering results. Further, we show that power law decay of
      specific temporal H-bond lifetime probability distributions is associated with
      librational and translational motions that occur on the time scale (~0.1 ps) of H
      bond breaking /re-forming dynamics. While our analysis is diffusion-free, the
      effect of diffusion on H-bond probability distributions where H-bonds are allowed
      to break and re-form, switching acceptors in between, is shown to result in
      neither exponential nor power law decay, similar to the reactive flux correlation
      function.

PMID- 24279453
TI  - An avirulence gene, AvrLmJ1, from the blackleg fungus, Leptosphaeria maculans,
      confers avirulence to Brassica juncea cultivars.
AB  - The fungus Leptosphaeria maculans causes blackleg of Brassica species. Here, we
      report the mapping and subsequent cloning of an avirulence gene from L. maculans.
      This gene, termed AvrLmJ1, confers avirulence towards all three Brassica juncea
      cultivars tested. Analysis of RNA-seq data showed that AvrLmJ1 is housed in a
      region of the L. maculans genome which contains only one gene that is highly
      expressed in planta. The closest genes are 57 and 33 kb away and, like other
      avirulence genes of L. maculans, AvrLmJ1 is located within an AT-rich, gene-poor
      region of the genome. The encoded protein is 141 amino acids, has a predicted
      signal peptide and is cysteine rich. Two virulent isolates contain a premature
      stop codon in AvrLmJ1. Complementation of an isolate that forms cotyledonary
      lesions on B. juncea with the wild-type allele of AvrLmJ1 confers avirulence
      towards all three B. juncea cultivars tested, suggesting that the gene may confer
      species-specific avirulence activity. 

PMID- 24279454
TI  - CO-releasing binuclear rhodium complexes as inhibitors of nitric oxide generation
      in stimulated macrophages.
AB  - Nontoxic CO-releasing dirhodium complexes act as inhibitors of NO in stimulated
      macrophage cells, suggesting that novel antiinflammatory treatments could involve
      the use of these types of binuclear complexes. 

PMID- 24279455
TI  - Tuning the degradation profiles of poly(L-lactide)-based materials through
      miscibility.
AB  - The effective use of biodegradable polymers relies on the ability to control the
      onset of and time needed for degradation. Preferably, the material properties
      should be retained throughout the intended time frame, and the material should
      degrade in a rapid and controlled manner afterward. The degradation profiles of
      polyester materials were controlled through their miscibility. Systems composed
      of PLLA blended with poly[(R,S)-3-hydroxybutyrate] (a-PHB) and polypropylene
      adipate (PPA) with various molar masses were prepared through extrusion. Three
      different systems were used: miscible (PLLA/a-PHB5 and PLLA/a-PHB20), partially
      miscible (PLLA/PPA5/comp and PLLA/PPA20/comp), and immiscible (PLLA/PPA5 and
      PLLA/PPA20) blends. These blends and their respective homopolymers were
      hydrolytically degraded in water at 37  degrees C for up to 1 year. The blends
      exhibited entirely different degradation profiles but showed no diversity between
      the total degradation times of the materials. PLLA presented a two-stage
      degradation profile with a rapid decrease in molar mass during the early stages
      of degradation, similar to the profile of PLLA/a-PHB5. PLLA/a-PHB20 presented a
      single, constant linear degradation profile. PLLA/PPA5 and PLLA/PPA20 showed
      completely opposing degradation profiles relative to PLLA, exhibiting a slow
      initial phase and a rapid decrease after a prolonged degradation time.
      PLLA/PPA5/comp and PLLA/PPA20/comp had degradation profiles between those of the
      miscible and the immiscible blends. The molar masses of the materials were
      approximately the same after 1 year of degradation despite their different
      profiles. The blend composition and topographical images captured at the last
      degradation time point demonstrate that the blending component was not leached
      out during the period of study. The hydrolytic stability of degradable polyester
      materials can be tailored to obtain different and predetermined degradation
      profiles for future applications. 

PMID- 24279456
TI  - Direct detection of S-palmitoylation by mass spectrometry.
AB  - Direct detection and quantification of protein/peptide palmitoylation by mass
      spectrometry (MS) is a challenging task because of the tendency of palmitoyl loss
      during sample preparation and tandem MS analysis. In addition, the large
      difference in hydrophobicity between the palmitoyl peptides and their unmodified
      counterparts could prevent their simultaneous analysis in a single liquid
      chromatography-MS experiment. Here, the stability of palmitoylation in several
      model palmitoyl peptides under different incubation and fragmentation conditions
      was investigated. It was found that the usual trypsin digestion protocol using
      dithiothreitol as the reducing agent in ammonium bicarbonate buffer could result
      in significant palmitoyl losses. Instead, it is recommended that sample
      preparation be performed in neutral tris buffer with tris(2
      carboxyethyl)phosphine as the reducing agent, conditions under which
      palmitoylation was largely preserved. For tandem MS analysis, collision-induced
      dissociation often led to facile palmitoyl loss, and electron capture
      dissociation frequently produced secondary side-chain losses remote from the
      backbone cleavage site, thus discouraging their use for accurate palmitoylation
      site determination. In contrast, the palmitoyl group was mostly preserved during
      electron transfer dissociation, which produced extensive inter-residue cleavage
      coverage, making it the ideal fragmentation method for palmitoyl peptide
      analysis. Finally, derivatization of the unmodified peptides with a
      perfluoroalkyl tag, N-[(3-perfluorooctyl)propyl] iodoacetamide, significantly
      increased their hydrophobicity, allowing them to be simultaneously analyzed with
      palmitoyl peptides for relative quantification of palmitoylation. 

PMID- 24279457
TI  - Bio-based coatings as potential barriers to chemical contaminants from recycled
      paper and board for food packaging.
AB  - Partition and diffusion experiments were carried out with paper and board samples
      coated with different biopolymers. The aim was to evaluate the physicochemical
      behaviour and barrier properties of bio-coatings against migration of typical
      contaminants from recycled paper packaging. Focus was directed towards water
      based, renewable biopolymers, such as modified starches (cationic starch and
      cationic waxy starch), plant and animal proteins (gluten and gelatine), poured
      onto paper with an automatic applicator. Additionally, a comparison with
      polyethylene-laminated paper was performed. Microstructural observations of the
      bio-coated paper allowed the characterisation of samples. From the partitioning
      studies, considerable differences in the adsorption behaviour of the selected
      contaminants between bio-coated or uncoated paper and air were highlighted. For
      both the polar and non-polar compounds considered (benzophenone and diisobutyl
      phthalate, respectively), the lowest values of partition coefficients were found
      when paper was bio-coated, making it evident that biopolymers acted as
      chemical/physical barriers towards these contaminants. These findings are
      discussed considering the characteristics of the tested biopolymers. Diffusion
      studies into the solid food simulant poly 2,6-diphenyl-p-phenylene oxide, also
      known as Tenax((r)), confirmed that all the tested biopolymers slowed down
      migration. The Weibull kinetic model was fitted to the experimental data to
      compare migration from paper and bio-coated paper. Values found for beta, an
      index determining the pattern of curvature, ranged from 1.1 to 1.7 for uncoated
      and polyethylene paper, whereas for bio-coated papers they ranged from 2.2 to
      4.9, corresponding to the presence of an evident lag phase due to barrier
      properties of the tested bio-coatings. 

PMID- 24279458
TI  - Collagen implants equipped with 'fish scale'-like nanoreservoirs of growth
      factors for bone regeneration.
AB  - Implants triggering rapid, robust and durable tissue regeneration are needed to
      shorten recovery times and decrease risks of postoperative complications for
      patients. Here, we describe active living collagen implants with highly promising
      bone regenerative properties. Bioactivity of the implants is obtained through the
      protective and stabilizing layer-by-layer immobilization of a protein growth
      factor in association with a polysaccharide (chitosan), within the form of
      nanocontainers decorating the collagen nanofibers. All components of the implants
      are US FDA approved. From both in vitro and in vivo evaluations, the
      sophisticated strategy described here should enhance, at a reduced cost, the
      safety and efficacy of the therapeutic implants in terms of large bone defects
      repair compared with current simplistic approaches based on the soaking of the
      implants with protein growth factor. 

PMID- 24279460
TI  - Comparison of surgical variables in cats undergoing single-incision laparoscopic
      ovariectomy using a LigaSure or extracorporeal suture versus open ovariectomy.
AB  - OBJECTIVE: To evaluate the applicability of single-incision laparoscopic
      ovariectomy (SILOVE) in cats using a single-incision laparoscopic port (SILP); to
      compare surgical time, complications, and postoperative pain after SILOVE using a
      LigaSure (SILOVE-LS) or extracorporeal suture (SILOVE-ECS), and open ovariectomy
      (open-OVE). STUDY DESIGN: Randomized, blinded, prospective study. ANIMALS:
      Healthy, domestic female cats (n = 24). METHODS: Cats underwent physical
      examination, packed cell volume, total solids and blood urea nitrogen analysis.
      Cats were randomly assigned to 1 of 3 groups: SILOVE-LS (n = 8), SILOVE-ECS (8)
      or open-OVE (8). Surgical time, complications, and postoperative pain scores were
      recorded. RESULTS: Single-incision laparoscopic ovariectomy was successful in (n
      = 8) SILOVE-LS cats and (n = 5) SILOVE-ECS cats. Surgical time was significantly
      longer for the SILOVE-ECS group compared with the SILOVE-LS (P < .0001) and open
      OVE (P < .0001) groups, which were not different (P = .55). Complications were
      more frequent in the SILOVE-ECS group and removal of the SILP was required to
      complete ovariectomy in 3 cats. Cumulative 4-hour pain scores were not different
      between groups. CONCLUSIONS: Single-incision laparoscopic ovariectomy using a
      SILP is a feasible method for OVE in cats. Single-incision laparoscopic
      ovariectomy using an extracorporeal suture is more time consuming and associated
      with more complications than either the SILOVE-LS or open-OVE methods.

PMID- 24279459
TI  - Inhibition of phosphoinositol 3 kinase contributes to nanoparticle-mediated
      exaggeration of endotoxin-induced leukocyte procoagulant activity.
AB  - AIM: Disseminated intravascular coagulation is an increasing concern for certain
      types of engineered nanomaterials. Recent studies have shed some light on the
      nanoparticle physicochemical properties contributing to this toxicity; however,
      the mechanisms are poorly understood. Leukocyte procoagulant activity (PCA) is a
      key factor contributing to the initiation of this toxicity. We have previously
      reported on the exaggeration of endotoxin-induced PCA by cationic dendrimers.
      Herein, we report an effort to discern the mechanism. MATERIALS & METHODS:
      Poly(amidoamine) dendrimers with various sizes and surface functionalities were
      studied in vitro by the recalcification test, flow cytometry and other relevant
      assays. RESULTS & CONCLUSION: Cationic dendrimers exaggerated endotoxin-induced
      PCA, but their anionic or neutral counterparts did not; the cationic charge
      prompts this phenomenon, but different cationic surface chemistries do not
      influence it. Cationic dendrimers and endotoxin differentially affect the PCA
      complex. The inhibition of phosphoinositol 3 kinase by dendrimers contributes to
      the exaggeration of the endotoxin-induced PCA.

PMID- 24279461
TI  - Triacylglycerols Determination by High-temperature Gas Chromatography in the
      Analysis of Vegetable Oils and Foods: A Review of the Past 10 Years.
AB  - The analysis of triacylglycerols by high-temperature gas chromatography, along
      the last 10 years has been reviewed in this paper. The interest in this topic has
      grown along the last years due to the triacylglycerols are the main components of
      oils and fats and they are being used for the characterization and authentication
      of foods products. The most commonly used procedures, including the official
      methodologies, applying high-temperature gas chromatographic techniques are
      shown. Their importance in the characterization of different kind of samples,
      vegetable oils, seeds, dairy products, etc., is considered. This review is not
      intended to be a comprehensive dissertation on the field of triacylglycerols
      analysis since that would require sufficient space to occupy a book in its own
      right. Rather, it will outline selected considerations and developments, where
      the technique has been applied.

PMID- 24279462
TI  - Binary classification of a large collection of environmental chemicals from
      estrogen receptor assays by quantitative structure-activity relationship and
      machine learning methods.
AB  - There are thousands of environmental chemicals subject to regulatory decisions
      for endocrine disrupting potential. The ToxCast and Tox21 programs have tested
      ~8200 chemicals in a broad screening panel of in vitro high-throughput screening
      (HTS) assays for estrogen receptor (ER) agonist and antagonist activity. The
      present work uses this large data set to develop in silico quantitative structure
      activity relationship (QSAR) models using machine learning (ML) methods and a
      novel approach to manage the imbalanced data distribution. Training compounds
      from the ToxCast project were categorized as active or inactive (binding or
      nonbinding) classes based on a composite ER Interaction Score derived from a
      collection of 13 ER in vitro assays. A total of 1537 chemicals from ToxCast were
      used to derive and optimize the binary classification models while 5073
      additional chemicals from the Tox21 project, evaluated in 2 of the 13 in vitro
      assays, were used to externally validate the model performance. In order to
      handle the imbalanced distribution of active and inactive chemicals, we developed
      a cluster-selection strategy to minimize information loss and increase predictive
      performance and compared this strategy to three currently popular techniques:
      cost-sensitive learning, oversampling of the minority class, and undersampling of
      the majority class. QSAR classification models were built to relate the molecular
      structures of chemicals to their ER activities using linear discriminant analysis
      (LDA), classification and regression trees (CART), and support vector machines
      (SVM) with 51 molecular descriptors from QikProp and 4328 bits of structural
      fingerprints as explanatory variables. A random forest (RF) feature selection
      method was employed to extract the structural features most relevant to the ER
      activity. The best model was obtained using SVM in combination with a subset of
      descriptors identified from a large set via the RF algorithm, which recognized
      the active and inactive compounds at the accuracies of 76.1% and 82.8% with a
      total accuracy of 81.6% on the internal test set and 70.8% on the external test
      set. These results demonstrate that a combination of high-quality experimental
      data and ML methods can lead to robust models that achieve excellent predictive
      accuracy, which are potentially useful for facilitating the virtual screening of
      chemicals for environmental risk assessment. 

PMID- 24279463
TI  - Regioselectivity of Larock heteroannulation: a contribution from electronic
      properties of diarylacetylenes.
AB  - A series of 2,3-diarylindoles were synthesized from 2-iodoaniline and
      unsymmetrical diarylacetylenes using the Larock heteroannulation.
      Diarylacetylenes bearing electron-withdrawing substituents lead to 2,3
      diarylindoles with substituted phenyl moieties at the 2-position as major
      products, while those with electron-donating groups preferably yield indole
      products with substituted phenyl moieties at the 3-position. The regioisomeric
      product ratios exhibit a clear correlation with Hammett sigma(p) values. DFT
      calculations reveal the origin of this effect, displaying smaller activation
      energy barriers for those pathways leading to the major regioisomer.

PMID- 24279464
TI  - Timely preparation for pre-emptive kidney transplantation: does the 'who' you see
      and 'where' you are influence the 'when' of listing?

PMID- 24279466
TI  - The educational gradient in marital disruption: a meta-analysis of European
      research findings.
AB  - A large number of empirical studies have investigated the effects of women's
      education on union dissolution in Europe, but results have varied substantially.
      This paper seeks to assess the relationship between educational attainment and
      the incidence of marital disruption by systematizing the existing empirical
      evidence. A quantitative literature review (a meta-analysis) was conducted to
      investigate the temporal change in the relationship, net of inter-study
      differences. The results point to a weakening of the positive educational
      gradient in marital disruption over time and even to a reversal in the direction
      of this gradient in some countries. The findings also show that the change in the
      educational gradient can be linked to an increase in access to divorce. Finally,
      the results suggest that women's empowerment has played an important role in
      changing the educational gradient, while the liberalization of divorce laws has
      not. 

PMID- 24279465
TI  - The Sybtraps: control of synaptobrevin traffic by synaptophysin, alpha-synuclein
      and AP-180.
AB  - Synaptobrevin II (sybII) is a key fusogenic molecule on synaptic vesicles (SVs)
      therefore the active maintenance of both its conformation and location in
      sufficient numbers on this organelle is critical in both mediating and sustaining
      neurotransmitter release. Recently three proteins have been identified having key
      roles in the presentation, trafficking and retrieval of sybII during the fusion
      and endocytosis of SVs. The nerve terminal protein alpha-synuclein catalyses
      sybII entry into SNARE complexes, whereas the monomeric adaptor protein AP-180 is
      required for sybII retrieval during SV endocytosis. Overarching these events is
      the tetraspan SV protein synaptophysin, which is a major sybII interaction
      partner on the SV. This review will evaluate recent studies to propose working
      models for the control of sybII traffic by synaptophysin and other Sybtraps
      (sybII trafficking partners) and suggest how dysfunction in sybII traffic may
      contribute to human disease. 

PMID- 24279468
TI  - Short-term impact of oral hygiene training package to Anganwadi workers on
      improving oral hygiene of preschool children in North Indian City.
AB  - BACKGROUND: Globally, dental caries is categorized in the list of public health
      problems in preschool children. In India, lack of availability and affordability
      of oral health enhances the cost of treatment and care. Empowering community
      workers like Anganwadi workers (AWWs) in oral health, and providing basic oral
      health awareness to the mothers through them can be feasible model. So, the
      present study was conducted to evaluate the short-term impact of Oral Hygiene
      Training Package (OHTP) to AWWs on improving oral hygiene of preschool children.
      METHODS: This before and after comparison field trial was done in Anganwadi
      centres (AWCs) of Chandigarh city, India. 534 children aged 36-72 months
      attending 21 AWCs were examined before and after imparting trainings to AWWs.
      OHTP was administered to AWWs, which consisted of power-point presentation and
      demonstrated the skills like proper brushing technique, plaque disclosure,
      flossing technique, gum massaging etc. The AWWs later imparted training to
      mothers in their respective AWCs. Post intervention data was collected after
      three months.Outcome measures were improvement in oral health status (plaque,
      debris, gingival health), oral habits (brushing, rinsing) and decrease in caries
      activity (Snyder test). RESULTS: Prevalence of dental caries was found to be
      48.3%. Only 4.1% of the population reported brushing twice which increased
      significantly to 9.9% post-intervention (p = 0.000). There was a significant
      decrease in debris (78.3% to 54.1%), and stage-1 plaque (75.5 to 66.5%) in the
      oral cavity. Caries activity by Snyder's test decreased from 48.2% to 31.2% (p =
      0.01) post-intervention. CONCLUSIONS: Controlled trials of using AWWs to improve
      oral hygiene appear to be justified. TRIAL REGISTRATION: CTRI/2012/07/002786.

PMID- 24279469
TI  - Host-guest complexes as water-soluble high-performance DNP polarizing agents.
AB  - Dynamic nuclear polarization (DNP) enhances the sensitivity of solid-state NMR
      (SSNMR) spectroscopy by orders of magnitude and, therefore, opens possibilities
      for novel applications from biology to materials science. This multitude of
      opportunities implicates a need for high-performance polarizing agents, which
      integrate specific physical and chemical features tailored for various
      applications. Here, we demonstrate that for the biradical bTbK in complex with
      captisol (CAP), a beta-cyclodextrin derivative, host-guest assembling offers a
      new and easily accessible approach for the development of new polarizing agents.
      In contrast to bTbK, the CAP-bTbK complex is water-soluble and shows
      significantly improved DNP performance compared to the commonly used DNP agent
      TOTAPOL. Furthermore, NMR and EPR data reveal improved electron and nuclear spin
      relaxation properties for bTbK within the host molecule. The numerous
      possibilities to functionalize host molecules will permit designing novel radical
      complexes targeting diverse applications. 

PMID- 24279470
TI  - The association of serum vascular endothelial growth factor and ferritin in
      diabetic microvascular disease.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in the
      pathogenesis of diabetic microvascular disease. Most diabetes patients have
      higher serum levels of ferritin that may participate in diabetic vascular
      complications through high oxidative stress induced by iron. However, the
      mechanistic link between ferritin and VEGF is obscure. The study investigated the
      association of VEGF and ferritin in patients with diabetic microvascular disease.
      PATIENTS AND METHODS: Sixty patients with type 2 diabetes mellitus (T2DM) and 26
      healthy individuals were selected in this study. Serum ferritin, VEGF,
      hematological parameters, and clinical data were assessed in this cohort. The
      Spearman rank method was used to evaluate the associations among them. RESULTS:
      Serum levels of VEGF and ferritin were significantly higher in diabetes patients
      compared with the controls; levels of both were elevated with development of the
      disease. There were positive correlations between VEGF and glucose levels and
      between VEGF and ferritin in diabetes groups, especially in patients with
      diabetic retinopathy. Positive correlations were also found between VEGF level
      and the parameters of age, hemoglobin, and albumin in patients with diabetes
      hypertension. CONCLUSIONS: Our data suggest that high ferritin levels in T2DM are
      closely related to the development of diabetic vascular complications through
      interaction with VEGF.

PMID- 24279471
TI  - Prognostic value of a nine-gene signature in glioma patients based on mRNA
      expression profiling.
AB  - INTRODUCTION: Gliomas are the most common primary brain tumors in adults and a
      significant cause of cancer-related mortality. A 9-gene signature was identified
      as a novel prognostic model reflecting survival situation obviously in gliomas.
      AIMS: To identify an mRNA expression signature to improve outcome prediction for
      patients with different glioma grades. RESULTS: We used whole-genome mRNA
      expression microarray data of 220 glioma samples of all grades from the Chinese
      Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set
      and data from Rembrandt and GSE16011 for validation sets. Data from every single
      grade were analyzed by the Kaplan-Meier method with a two-sided log-rank test.
      Univariate Cox regression and linear risk score formula were applied to derive a
      gene signature with better prognostic performance. We found that patients who had
      high risk score according to the signature had poor overall survival compared
      with patients who had low risk score. Highly expressed genes in the high-risk
      group were analyzed by gene ontology (GO) and gene set variation analysis (GSVA).
      As a result, the reason for the divisibility of gliomas was likely due to cell
      life processes and adhesion. CONCLUSION: This 9-gene-signature prediction model
      provided a more accurate predictor of prognosis that denoted patients with high
      risk score have poor outcome. Moreover, these risk models based on defined
      molecular profiles showed the considerable prospect in personalized cancer
      management.

PMID- 24279472
TI  - Retrospective investigation of testosterone undecanoate depot for the long-term
      treatment of male hypogonadism in clinical practice.
AB  - INTRODUCTION: Testosterone undecanoate depot (TUD) administered intramuscularly
      is an effective form of testosterone replacement therapy (TRT) for male
      hypogonadism. Because of the ease of administration, TUD therapy may be
      preferable to subcutaneously implanted extended release T pellet implants (TI).
      AIM: The primary objective was to retrospectively assess the efficacy and safety
      of long-term (>= 2 years therapy) TUD therapy in the clinical setting. The
      secondary objective was to retrospectively compare TUD with TI therapy. METHODS:
      Retrospective data were collected from the Waikato Hospital Endocrine Database
      for 179 hypogonadal men treated with TUD for >= 2 years from 1998-2011, with 124
      of these men receiving previous TI therapy. MAIN OUTCOME MEASURES: The main
      outcome measure for efficacy was serum trough total testosterone (TT), and for
      safety an increase in hemoglobin (Hb) and/or hematocrit (Hct), rise in prostate
      specific antigen (PSA) and/or prostatic biopsy and alteration in body mass index
      and lipid profile. Additional outcome measures were changes in the dosing and/or
      interval regimens for TUD therapy. RESULTS: Overall, 72% of trough TT levels were
      in the normal range for TUD therapy compared with 53% of trough TT levels during
      TI therapy. TUD therapy was well tolerated with 162 men (90.5%) completing 2
      years of treatment, and only seven men (3.9%) stopping TUD because of adverse
      effects. A rise in Hb and/or Hct occurred in 25 men (14%), and a significant rise
      in PSA in 20 men (13%) at some stage during TUD therapy. At 2 years, 91% of men
      received the standard 1,000 mg TUD dose with 66% at the standard dosing interval
      of 10-14 weekly. CONCLUSIONS: TUD is an efficacious, safe, and well tolerated
      form of TRT, and individual optimisation of the dose and/or interval is only
      required in the minority of men. Particularly given the ease of administration,
      TUD was the preferred TRT for both patients and clinicians.

PMID- 24279473
TI  - Active demethylation in mouse zygotes involves cytosine deamination and base
      excision repair.
AB  - BACKGROUND: DNA methylation in mammals is an epigenetic mark necessary for normal
      embryogenesis. During development active loss of methylation occurs in the male
      pronucleus during the first cell cycle after fertilisation. This is accompanied
      by major chromatin remodelling and generates a marked asymmetry between the
      paternal and maternal genomes. The mechanism(s) by which this is achieved
      implicate, among others, base excision repair (BER) components and more recently
      a major role for TET3 hydroxylase. To investigate these methylation dynamics
      further we have analysed DNA methylation and hydroxymethylation in fertilised
      mouse oocytes by indirect immunofluorescence (IF) and evaluated the relative
      contribution of different candidate factors for active demethylation in knock-out
      zygotes by three-dimensional imaging and IF semi-quantification. RESULTS: We find
      two distinct phases of loss of paternal methylation in the zygote, one prior to
      and another coincident with, but not dependent on, DNA replication. TET3-mediated
      hydroxymethylation is limited to the replication associated second phase of
      demethylation. Analysis of cytosine deaminase (AID) null fertilised oocytes
      revealed a role for this enzyme in the second phase of loss of paternal
      methylation, which is independent from hydroxymethylation. Investigation into the
      possible repair pathways involved supports a role for AID-mediated cytosine
      deamination with subsequent U-G mismatch long-patch BER by UNG2 while no evidence
      could be found for an involvement of TDG. CONCLUSIONS: There are two observable
      phases of DNA demethylation in the mouse zygote, before and coincident with DNA
      replication. TET3 is only involved in the second phase of loss of methylation.
      Cytosine deamination and long-patch BER mediated by UNG2 appear to independently
      contribute to this second phase of active demethylation. Further work will be
      necessary to elucidate the mechanism(s) involved in the first phase of active
      demethylation that will potentially involve activities required for early sperm
      chromatin remodelling.

PMID- 24279474
TI  - Characterization of Plp, a phosphatidylcholine-specific phospholipase and
      hemolysin of Vibrio anguillarum.
AB  - BACKGROUND: Vibrio anguillarum is the causative agent of vibriosis in fish.
      Several extracellular proteins secreted by V. anguillarum have been shown to
      contribute to virulence. While two hemolysin gene clusters, vah1-plp and
      rtxACHBDE, have been previously identified and described, the activities of the
      protein encoded by the plp gene were not known. Here we describe the biochemical
      activities of the plp-encoded protein and its role in pathogenesis. RESULTS: The
      plp gene, one of the components in vah1 cluster, encodes a 416-amino-acid protein
      (Plp), which has homology to lipolytic enzymes containing the catalytic site
      amino acid signature SGNH. Hemolytic activity of the plp mutant increased 2-3
      fold on sheep blood agar indicating that plp represses vah1; however, hemolytic
      activity of the plp mutant decreased by 2-3-fold on fish blood agar suggesting
      that Plp has different effects against erythrocytes from different species. His6
      tagged recombinant Plp protein (rPlp) was over-expressed in E. coli. Purified and
      re-folded active rPlp exhibited phospholipase A2 activity against
      phosphatidylcholine and no activity against phosphatidylserine,
      phosphatidylethanolamine, or sphingomyelin. Characterization of rPlp revealed
      broad optimal activities at pH 5-9 and at temperatures of 30-64 degrees C.
      Divalent cations and metal chelators did not affect activity of rPlp. We also
      demonstrated that Plp was secreted using thin layer chromatography and immunoblot
      analysis. Additionally, rPlp had strong hemolytic activity towards rainbow trout
      erythrocytes, but not to sheep erythrocytes suggesting that rPlp is optimized for
      lysis of phosphatidylcholine-rich fish erythrocytes. Further, only the loss of
      the plp gene had a significant effect on hemolytic activity of culture
      supernatant on fish erythrocytes, while the loss of rtxA and/or vah1 had little
      effect. However, V. anguillarum strains with mutations in plp or in plp and vah1
      exhibited no significant reduction in virulence compared to the wild type strain
      when used to infect rainbow trout. CONCLUSION: The plp gene of V. anguillarum
      encoding a phospholipase with A2 activity is specific for phosphatidylcholine
      and, therefore, able to lyse fish erythrocytes, but not sheep erythrocytes.
      Mutation of plp does not affect the virulence of V. anguillarum in rainbow trout.

PMID- 24279475
TI  - Clinical outcomes of locked plating of distal femoral fractures in a
      retrospective cohort.
AB  - PURPOSE: Locked plating (LP) of distal femoral fractures has become very popular.
      Despite technique suggestions from anecdotal and some early reports, knowledge
      about risk factors for failure, nonunion (NU), and revision is limited. The
      purpose of this study was to analyze the complications and clinical outcomes of
      LP treatment for distal femoral fractures. MATERIALS AND METHODS: From two trauma
      centers, 243 consecutive surgically treated distal femoral fractures (AO/OTA 33)
      were retrospectively identified. Of these, 111 fractures in 106 patients (53.8%
      female) underwent locked plate fixation. They had an average age of 54 years
      (range 18 to 95 years): 34.2% were obese, 18.9% were smokers, and 18.9% were
      diabetic. Open fractures were present in 40.5% with 79.5% Gustilo type III.
      Fixation constructs for plate length, working length, and screw concentration
      were delineated. Nonunion and/or infection, and implant failure were used as
      outcome complication variables. Outcome was based on surgical method and
      addressed according to Pritchett for reduction, range of motion, and pain.
      RESULTS: Eighty-three (74.8%) of the fractures healed after the index procedure.
      Twenty (18.0%) of the patients developed a NU. Four of 20 (20%) resulted in a
      recalcitrant NU. Length of comminution did not correlate to NU (p = 0.180).
      Closed injuries had a higher tendency to heal after the index procedure than open
      injuries (p = 0.057). Closed and minimally open (Gustilo/Anderson types I and II)
      fractures healed at a significantly higher rate after the index procedure
      compared to type III open fractures (80.0% versus 61.3%, p = 0.041). Eleven
      fractures (9.9%) developed hardware failure. Fewer nonunions were found in the
      submuscular group (10.7%) compared to open reduction (32.0%) (p = 0.023).
      Fractures above total knee arthroplasties had a significantly greater rate of
      failed hardware (p = 0.040) and worse clinical outcome according to Pritchett (p
      = 0.040). Loss of fixation was related to pain (F = 3.19, p = 0.046) and a
      tendency to worse outcome (F = 2.43, p = 0.071). No relationship was found
      between nonunion and working length. CONCLUSION: Despite modern fixation
      techniques, distal femoral fractures often result in persistent disability and
      worse clinical outcomes. Soft tissue management seems to be important.
      Submuscular plate insertion reduced the nonunion rate. Preexisting total knee
      arthroplasty increased the risk of hardware failure. Further studies determining
      factors that improve outcome are warranted.

PMID- 24279476
TI  - The role of physical activity, body mass index and maturity status in body
      related perceptions and self-esteem of adolescents.
AB  - BACKGROUND: Adolescence represents a transitional period which is marked by
      physical, social and psychological changes. Changes in body shape and physical
      activity especially alter and shape the psychological well-being of adolescents.
      AIM: The purpose of this study was to determine the role of physical activity
      level, body mass index and maturity status in body-related perception and self
      esteem of 11-18 years old adolescents. SUBJECTS AND METHODS: A total of 1012
      adolescents participated in this study. The "Social Physique Anxiety Scale",
      "Body Image Satisfaction Scale", "Physical Self-Perception Profile for Children"
      and "Rosenberg Self-Esteem Inventory" were administered. Physical activity level
      and body mass index were assessed using the "Physical Activity Questionnaire" and
      "Bioelectrical Impedance Analyzer", respectively. RESULTS: Regression analysis
      indicated that body mass index was the only predictor of perceived body
      attractiveness, social physique anxiety, body image satisfaction and self-esteem
      for female adolescents. For male adolescents, both physical activity and body
      mass index were correlated with perceived body attractiveness and social physique
      anxiety. Pubertal status were not correlated with self-esteem and body-related
      perceptions for both males and females adolescents. CONCLUSION: In summary, body
      mass index and physical activity plays an important role in body-related
      perceptions and self-esteem of adolescents.

PMID- 24279477
TI  - Invisible economics of nursing: analysis of a hospital bill through a Foucauldian
      perspective.

PMID- 24279478
TI  - Vitamin C and common cold-induced asthma: a systematic review and statistical
      analysis.
AB  - BACKGROUND: Asthma exacerbations are often induced by the common cold, which, in
      turn, can be alleviated by vitamin C. OBJECTIVE: To investigate whether vitamin C
      administration influences common cold-induced asthma. METHODS: Systematic review
      and statistical analysis of the identified trials. Medline, Scopus and Cochrane
      Central were searched for studies that give information on the effects of vitamin
      C on common cold-induced asthma. All clinically relevant outcomes related to
      asthma were included in this review. The estimates of vitamin C effect and their
      confidence intervals [CI] were calculated for the included studies. RESULTS:
      Three studies that were relevant for examining the role of vitamin C on common
      cold-induced asthma were identified. The three studies had a total of 79
      participants. Two studies were randomized double-blind placebo-controlled trials.
      A study in Nigeria on asthmatics whose asthma attacks were precipitated by
      respiratory infections found that 1 g/day vitamin C decreased the occurrence of
      asthma attacks by 78% (95% CI: 19% to 94%). A cross-over study in former East
      Germany on patients who had infection-related asthma found that 5 g/day vitamin C
      decreased the proportion of participants who had bronchial hypersensitivity to
      histamine by 52 percentage points (95% CI: 25 to 71). The third study did not use
      a placebo. Administration of a single dose of 1 gram of vitamin C to Italian non
      asthmatic common cold patients increased the provocative concentration of
      histamine (PC20) 3.2-fold (95% CI: 2.0 to 5.1), but the vitamin C effect was
      significantly less when the same participants did not suffer from the common
      cold. CONCLUSIONS: The three reviewed studies differed substantially in their
      methods, settings and outcomes. Each of them found benefits from the
      administration of vitamin C; either against asthma attacks or against bronchial
      hypersensitivity, the latter of which is a characteristic of asthma. Given the
      evidence suggesting that vitamin C alleviates common cold symptoms and the
      findings of this systematic review, it may be reasonable for asthmatic patients
      to test vitamin C on an individual basis, if they have exacerbations of asthma
      caused by respiratory infections. More research on the role of vitamin C on
      common cold-induced asthma is needed.

PMID- 24279479
TI  - Establishing magnetic resonance images orientation for the EADC-ADNI manual
      hippocampal segmentation protocol.
AB  - BACKGROUND AND PURPOSE: An effort to define and validate a Harmonized Protocol
      for standard hippocampal segmentation is being carried out. We wished to estimate
      the effect of magnetic resonance image (MRI) spatial orientation on manual
      hippocampal segmentations to define optimal standard orientation of MRIs for
      hippocampal volumetry. METHODS: Three expert tracers segmented twice the
      hippocampi of 10 ADNI subjects on MRI slices oriented perpendicular to the
      anterior-posterior commissure (AC-PC) line and the long hippocampal axes plane,
      following internationally harmonized landmarks. We computed intra and interrater
      reliability figures for total volumes and similarity coefficients. RESULTS: Total
      volume reliability was similar for both orientations. Similarity coefficients
      were significantly higher for the AC-PC orientation (exact P = 0.002).
      DISCUSSION: These data show that AC-PC orientation is slightly more reliable for
      manual segmentations, possibly due to better visualization of the cerebrospinal
      fluid spaces separating hippocampal head and amygdala. A Delphi panel of experts
      has used these data to decide on the optimal orientation for a Harmonized
      Protocol for hippocampal segmentation.

PMID- 24279480
TI  - Uptake of engineered gold nanoparticles into mammalian cells.

PMID- 24279481
TI  - Neuropsychological profile of duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized
      by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an
      estimated prevalence of 1 in 3,500 male live births. This disease has long been
      associated with intellectual impairment. Research has shown that boys with DMD
      have variable intellectual performance, indicating the presence of specific
      cognitive deficits. The aim of the study was to use a battery of intelligence,
      learning, and memory tests to identify a neuropsychological profile in boys with
      DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old
      were evaluated using the Wechsler Intelligence Scale for Children-Third Edition,
      Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data
      were interpreted using means, standard deviations, percentages, and percentiles.
      Normative data were also used for further interpretation. The results showed that
      boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to
      be lower than Performance IQ (92.64). There was evidence of impaired performance
      on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension
      Indexes. Specific deficits in information processing, complex attention,
      immediate verbal memory span, verbal working memory, verbal comprehension,
      vocabulary, visuoconstruction ability, and verbal learning and encoding were
      observed. However, perceptional organization, general fund of information,
      abstract reasoning, visual discrimination and acuity, visual learning and memory,
      and verbal memory were adequate. The neuropsychological findings support the
      hypothesis that these children have specific cognitive deficits as opposed to a
      global intellectual deficit. 

PMID- 24279483
TI  - Development of a novel method for unraveling the origin of natron flux used in
      Roman glass production based on B isotopic analysis via multicollector
      inductively coupled plasma mass spectrometry.
AB  - The provenance of the flux raw material used in the manufacturing of Roman glass
      is an understudied topic in archaeology. Whether one or multiple sources of
      natron mineral salts were exploited during this period is still open for debate,
      largely because of the lack of a good provenance indicator. The flux is the major
      source of B in Roman glass. Therefore, B isotopic analysis of a sufficiently
      large collection and variety (origin and age) of such glass samples might give an
      indication of the number of flux sources used. For this purpose, a method based
      on acid digestion, chromatographic B isolation and B isotopic analysis using
      multicollector inductively coupled plasma mass spectrometry was developed. B
      isolation was accomplished using a combination of strong cation exchange and
      strong anion exchange chromatography. Although the B fraction was not completely
      matrix-free, the remaining Sb was shown not to affect the delta(11)B result. The
      method was validated using obsidian and archaeological glass samples that were
      stripped of their B content, after which an isotopic reference material with
      known B isotopic composition was added. Absence of artificial B isotope
      fractionation was demonstrated, and the total uncertainty was shown to be <20/00.
      A proof-of-concept application to natron glass samples showed a narrow range of
      delta(11)B, whereas first results for natron salt samples do show a larger
      difference in delta(11)B. These results suggest the use of only one natron source
      or of several sources with similar delta(11)B. This indicates that B isotopic
      analysis is a promising tool for the provenance determination of this flux raw
      material. 

PMID- 24279482
TI  - Prevalence of thyrotropin receptor germline mutations and clinical courses in 89
      hyperthyroid patients with diffuse goiter and negative anti-thyrotropin receptor
      antibodies.
AB  - BACKGROUND: We studied the frequency of thyrotropin (TSH) receptor mutations in
      hyperthyroid patients with diffuse goiter and negative TSH receptor antibodies
      (TRAb), and the clinical pictures of the hyperthyroid patients in the presence
      and absence of mutations. PATIENTS AND METHODS: From 2003 through 2012, 89
      hyperthyroid patients with diffuse goiter and negative TRAb based on a second- or
      third-generation assay underwent sequence analysis of the TSH receptor gene from
      peripheral leukocytes. The outcome of hyperthyroidism in patients with a TSH
      receptor mutation and their affected family members was compared with that in
      patients without any mutation after a 1-10-year follow-up. RESULTS: Germline
      mutations of the TSH receptor occurred in 4 of the 89 patients (4.5%), including
      3 definitive constitutively activating mutations (L512Q, E575K, and D617Y). The
      main difference in the clinical outcome of hyperthyroidism was that no patients
      with a TSH receptor mutation achieved euthyroidism throughout the follow-up,
      while 23.5% of patients without any mutation entered remission. The progression
      from subclinical to overt hyperthyroidism was not significantly different between
      patients with or without a mutation. Meanwhile, 10.3% of TRAb-negative patients
      without any TSH receptor mutation developed TRAb-positive Graves' hyperthyroidism
      during the follow-up. CONCLUSIONS: The prevalence of nonautoimmune
      hyperthyroidism with TSH receptor mutations is lower than that of latent Graves'
      disease in TRAb-negative patients with hyperthyroidism. However, all affected
      patients with a TSH receptor mutation showed persistent hyperthyroidism
      regardless of subclinical or overt hyperthyroidism throughout the follow-up.

PMID- 24279484
TI  - Microbial biofabrication for nanomedicine: biomaterials, nanoparticles and
      beyond.

PMID- 24279485
TI  - Ferritin-based nanoprobes: promising materials for tumor imaging.

PMID- 24279486
TI  - Solid lipid nanoparticle-incorporated gel: the future treatment for skin
      infections?

PMID- 24279487
TI  - Novel nanoparticle-based method for rapid screening of blood clotting.

PMID- 24279488
TI  - Application of spirothiopyran to generate light-induced self-assembly of metal
      nanoparticles.

PMID- 24279489
TI  - Nanomedical research in Australia and New Zealand.
AB  - Although Australia and New Zealand have a combined population of less than 30
      million, they have an active and interlinked community of nanomedical
      researchers. This report provides a synopsis and update on this network with a
      view to identifying the main topics of interest and their likely future
      trajectories. In addition, our report may also serve to alert others to
      opportunities for joint projects. Australian and New Zealand researchers are
      engaged in most of the possible nanomedical topics, but the majority of interest
      is focused on drug and nucleic acid delivery using nanoparticles or nanoporous
      constructs. There are, however, smaller programs directed at hyperthermal therapy
      and radiotherapy, various kinds of diagnostic tests and regenerative
      technologies. 

PMID- 24279490
TI  - Progress in the characterization and safety evaluation of engineered inorganic
      nanomaterials in food.
AB  - Nanotechnology has stepped into the food industry, from the farm to the table at
      home, in order to improve the taste and nutritional value, extend the shelf-life
      and monitor the food quality. In fact, as consumers we have already been in
      contact, via oral exposure, with a number of food products containing engineered
      nanomaterials (ENMs) more often than most people think. However, the fate of ENMs
      after entering the GI tract of the human body is not yet clearly understood.
      Hence, the related safety issue is raised, and attracts much attention and wide
      debate from the public, even including protest demonstrations against
      nanotechnology in food. In this review, we summarize the up-to-date information
      about the characterization and safety evaluation of common inorganic ENMs (with a
      focus on silver, titanium dioxide, silica and zinc oxide nanoparticles) in food.
      Based on the literature, a whole scenario of the safety issue of these ENMs in
      food and an outlook on the future studies are given. 

PMID- 24279492
TI  - Biomedical applications of nanodiamonds in imaging and therapy.
AB  - Nanodiamonds have attracted remarkable scientific attention for bioimaging and
      therapeutic applications owing to their low toxicity with many cell lines,
      convenient surface properties and stable fluorescence without photobleaching.
      Newer techniques are being applied to enhance fluorescence. Interest is also
      growing in exploring the possibilities for modifying the nanodiamond surface and
      functionalities by attaching various biomolecules of interest for interaction
      with the targets. The potential of Raman spectroscopy and fluorescence properties
      of nanodiamonds has been explored for bioimaging and drug delivery tracing. The
      interest in nanodiamonds' biological/medical application appears to be continuing
      with enhanced focus. In this review an attempt is made to capture the scope,
      spirit and recent developments in the field of nanodiamonds for biomedical
      applications. 

PMID- 24279491
TI  - Biomedical applications of functionalized hollow mesoporous silica nanoparticles:
      focusing on molecular imaging.
AB  - Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each
      original mesoporous silica nanoparticle, have recently gained increasing interest
      owing to their tremendous potential for cancer imaging and therapy. The last
      several years have witnessed a rapid development in the engineering of
      functionalized HMSNs (i.e., f-HMSNs), with various types of inorganic functional
      nanocrystals integrated into the system for imaging and therapeutic applications.
      In this article, we summarize the recent progress in the design and biological
      applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly
      used synthetic strategies for the generation of high quality HMSNs will be
      discussed in detail, followed by a systematic review of engineered f-HMSNs for
      optical, PET, MRI and ultrasound imaging in preclinical studies. Finally, we
      discuss the challenges and future research directions regarding the use of f
      HMSNs for cancer imaging and therapy. 

PMID- 24279493
TI  - Strategies for improving mucosal drug delivery.
AB  - Within this review we will provide a comprehensive understanding in order to
      improve existing strategies and to develop new systems to lower the barrier for
      improving mucosal drug delivery. Mucosal administration of drugs achieves a
      therapeutical effect as the permeation of significant amounts of a drug is
      permitted through the absorption membrane. The absorption membrane relies on the
      mucosal layer and the epithelial tissue. In order to overcome barriers, drug
      delivery systems have to exhibit various functions and features, such as
      mucoadhesive and protective activity, solubility improving, permeation and uptake
      enhancing, and drug release controlling properties. This review also aims to
      provide an insight of well-distinguished strategies to date, as well as provide a
      focus on the enhancement of membrane permeability. Furthermore, since the
      development and functions of drug delivery systems exert a high influence on the
      ability of drug permeation through membrane, these considerations will also be
      discussed in this review. 

PMID- 24279496
TI  - Regio- and diastereoselective Cu-mediated trifluoromethylation of functionalized
      alkenes.
AB  - alpha- and beta-substituted N,N-diethylacrylamides undergo copper-mediated direct
      beta-trifluoromethylation. The amide moiety acts as a directing group for the
      regio- and the stereo-controlled introduction of the trifluoromethyl group. The
      reaction is carried out under acidic conditions in the presence of Umemoto's
      reagent. This method does not require prefunctionalized substrates and delivers
      excellent stereoselectivity. 

PMID- 24279497
TI  - Lipid Oxidation in Low-moisture Food: A Review.
AB  - Overly high intake of saturated fat is an international problem contributing to
      global health issues. Low-moisture snacks account for a nutritionally significant
      proportion of the saturated fat in the diet, making these foods a key target for
      improving consumers' health. However, it is not currently feasible to maintain
      the same oxidative shelf life when replacing saturated fats with unsaturated
      fats, which are generally perceived to be more heart-healthy. This article
      summarizes current theories and available research on lipid oxidation in low
      moisture foods in order to lay the groundwork for new lipid oxidation rate
      reduction strategies. Research deficits needing attention and new methods for
      assessing lipid oxidation in low-moisture foods are also discussed.

PMID- 24279498
TI  - Engineering antimicrobial peptides with improved antimicrobial and hemolytic
      activities.
AB  - The rapid rise of antibiotic resistance in pathogens becomes a serious and
      growing threat to medicine and public health. Naturally occurring antimicrobial
      peptides (AMPs) are an important line of defense in the immune system against
      invading bacteria and microbial infection. In this work, we present a combined
      computational and experimental study of the biological activity and membrane
      interaction of the computationally designed Bac2A-based peptide library. We used
      the MARTINI coarse-grained molecular dynamics with adaptive biasing force method
      and the umbrella sampling technique to investigate the translocation of a total
      of 91 peptides with different amino acid substitutions through a mixed anionic
      POPE/POPG (3:1) bilayer and a neutral POPC bilayer, which mimic the bacterial
      inner membrane and the human red blood cell (hRBC) membrane, respectively.
      Potential of mean force (PMF, free energy profile) was obtained to measure the
      free energy barrier required to transfer the peptides from the bulk water phase
      to the water-membrane interface and to the bilayer interior. Different PMF
      profiles can indeed identify different membrane insertion scenarios by mapping
      out peptide-lipid energy landscapes, which are correlated with antimicrobial
      activity and hemolytic activity. Computationally designed peptides were further
      tested experimentally for their antimicrobial and hemolytic activities using
      bacteria growth inhibition assay and hemolysis assay. Comparison of PMF data with
      cell assay results reveals a good correlation of the peptides between predictive
      transmembrane activity and antimicrobial/hemolytic activity. Moreover, the most
      active mutants with the balanced substitutions of positively charged Arg and
      hydrophobic Trp residues at specific positions were discovered to achieve the
      improved antimicrobial activity while minimizing red blood cell lysis. Such
      substitutions provide more effective and cooperative interactions to distinguish
      the peptide interaction with different lipid bilayers. This work provides a
      useful computational tool to better understand the mechanism and energetics of
      membrane insertion of AMPs and to rationally design more effective AMPs. 

PMID- 24279499
TI  - Pyruvate utilization by a chemolithoautotrophic epsilonproteobacterial key player
      of pelagic Baltic Sea redoxclines.
AB  - Pelagic redoxclines of the central Baltic Sea are dominated by the
      epsilonproteobacterial group Sulfurimonas GD17, considered to be the major driver
      of chemolithoautotrophic denitrification in this habitat. Autecological
      investigations of a recently isolated representative of this environmental group,
      Sulfurimonas gotlandica str. GD1(T), demonstrated that the bacterium grows best
      under sulfur-oxidizing, denitrifying conditions. However, in the presence of
      bicarbonate, this strain is able to use pyruvate as both an additional carbon
      source and an alternative electron donor. These observations suggested that the
      environmental group GD17 actively metabolizes organic substrates in situ. To
      examine this possibility, we used RNA-based stable isotope probing (RNA-SIP) on a
      natural redoxcline community provided with 13C-labeled pyruvate. While in this
      experiment, we were able to identify putative heterotrophic microorganisms, the
      uptake of 13C-pyruvate in GD17 nucleic acids could not be established. To resolve
      these contradictory findings, combined incorporation experiments with 14C- and
      13C-labeled pyruvate were carried out in cells of strain GD1(T) cultivated under
      chemolithoautotrophic conditions, which favor pyruvate uptake rather than
      oxidation. An analysis of the labeled biomolecules revealed that pyruvate was
      mostly incorporated in cellular components such as amino acids, whose synthesis
      requires only minimal transformation. Carbon transfer into nucleic acids was not
      observed, explaining the inability of RNA-SIP to detect pyruvate incorporation by
      strain GD1(T) and the environmental group GD17. Together, these findings suggest
      that by integrating organic compounds such as pyruvate into cellular components
      S. gotlandica GD1(T) is able to replenish chemolithoautotrophic growth and thus
      ensure its survival in nutrient-limited habitats such as marine pelagic
      redoxclines.

PMID- 24279502
TI  - The potential role of ex vivo lung perfusion for the diagnosis of infection
      before lung transplantation.

PMID- 24279503
TI  - Universal correlation between fibril width and quantum efficiency in
      diketopyrrolopyrrole-based polymer solar cells.
AB  - For a series of six diketopyrrolopyrrole (DPP)-based conjugated polymers, we
      establish a direct correlation between their external quantum efficiencies (EQE)
      in organic solar cells and the fibrillar microstructure in the blend. The
      polymers consist of electron-deficient DPP units, carrying long branched 2'
      decyltetradecyl (DT) side chains for solubility, that alternate along the main
      chain with electron-rich aromatic segments comprising benzene, thiophene, or
      fused aromatic rings. The high molecular weight DT-DPP polymers were incorporated
      in bulk heterojunction solar cells with [6,6]-phenyl-C71-butyric acid methyl
      ester ([70]PCBM) as acceptor. The morphology of the DT-DPP:[70]PCBM blends is
      characterized by a semicrystalline fibrillar microstructure with fibril widths
      between 4.5 and 30 nm as evidenced from transmission electron microscopy. A clear
      correlation is found between the widths of the fibrils and the EQE for photon to
      electron conversion. The highest EQEs (60%) and power conversion efficiencies
      (7.1%) are obtained for polymers with fibril widths less than 12 nm. For blends
      with fibrils wider than 12 nm, the EQE is low because exciton diffusion becomes
      limiting for charge generation. Interestingly, the correlation found here matches
      with previous data on related DPP-based polymers. This suggests that for this
      class of materials the relation between fiber width and EQE is universal. The
      fiber width is largely correlated with the solubility of the polymers, with less
      soluble DPP-based polymers giving narrower fibrils. 

PMID- 24279500
TI  - Enriching the pore: splendid complexity from humble origins.
AB  - The nucleus is the defining intracellular organelle of eukaryotic cells and
      represents a major structural innovation that differentiates the eukaryotic and
      prokaryotic cellular form. The presence of a nuclear envelope (NE) encapsulating
      the nucleus necessitates a mechanism for interchange between the contents of the
      nuclear interior and the cytoplasm, which is mediated via the nuclear pore
      complex (NPC), a large protein assembly residing in nuclear pores in the NE.
      Recent advances have begun to map the structure and functions of the NPC in
      multiple organisms, and to allow reconstruction of some of the evolutionary
      events that underpin the modern NPC form, highlighting common and differential
      NPC features across the eukaryotes. Here we discuss some of these advances and
      the questions being pursued, consider how the evolution of the NPC has been
      constrained, and finally propose a model for how the NPC evolved. 

PMID- 24279504
TI  - Dental caries status of Dai preschool children in Yunnan Province, China.
AB  - BACKGROUND: The Dai people, one of the ethnic minorities in China, have a
      population of 1,260,000. They have the same origin as one of the main ethnic
      groups of Laos and Thailand. Most of the Dai live in Yunnan province, which is
      located in the less-developed southwestern part of China. This study aimed to
      describe the oral health status of Dai preschool children in China and the
      factors that influence their oral health status. METHODS: An oral health survey
      was performed between 2011 and 2012 to select Dai five-year-old children using
      multi-stage stratified sampling in Yunnan. Their dental caries experience was
      measured using the "dmft" index, and severe caries was assessed using the "pa"
      index, which is modified from the "pufa" index. Oral hygiene status was assessed
      using the visual plaque index (VPI). A questionnaire to study the children's
      socio-demographic background and oral health-related behaviours was completed by
      the children's parents. RESULTS: A total of 833 children were examined. Their
      caries prevalence was 89% and 49% of the children had carious tooth with pulp
      involvement. The mean (SD) dmft score was 7.0 (5.3). Higher dmft scores were
      found among children who were girls, were currently bottle-fed, took daily sweet
      snacks, had higher VPI scores, and had visited a dentist within the last year.
      CONCLUSIONS: The caries prevalence and experience of the five-year-old Dai
      children in Yunnan, China was high, and almost half had severe caries. The caries
      experience was associated with gender, snack habits, dental visit habits, and
      oral hygiene status.

PMID- 24279506
TI  - Recently patented transcatheter aortic valves in clinical trials.
AB  - The most widely used heart valve worldwide is the Edwards Sapien, which currently
      has 60% of the worldwide transcatheter aortic valve implantation (TAVI) market.
      The CoreValve is next in line in popularity, encompassing 35% of the worldwide
      TAVI market. Although these two valves dominate the TAVI market, a number of
      newer transcatheter valves have been introduced and others are in early clinical
      evaluation. The new valves are designed to reduce catheter delivery diameter,
      improve ease of positioning and sealing, and facilitate repositioning or removal.
      The most recent transcatheter valves for transapical use include Acurate TA
      (Symetis), Engager (Medtronic), and JenaValve the Portico (St Jude), Sadra Lotus
      Medical (Boston Scientific), and the Direct Flow Medical. These new inventions
      may introduce more effective treatment options for high-risk patients with severe
      aortic stenosis. Improvements in transcatheter valves and the developing
      variability among them may allow for more tailored approaches with respect to
      patient's anatomy, while giving operators the opportunity to choose devices they
      feel more comfortable with. Moreover, introducing new devices to the market will
      create a competitive environment among producers that will reduce high prices and
      expand availability. The present review article includes a discussion of recent
      patents related to Transcatheter Aortic Valves. 

PMID- 24279505
TI  - Surgery for primary filum terminale ependymomas: outcome and prognostic factors.
AB  - INTRODUCTION: Primary filum terminale ependymoma (PFTE) is a unique type of
      ependymomas and locates on extramedullary site. However, the clinical features
      and prognostic factors of PFTE are still unknown due to its rarity. AIM: This
      study aimed to evaluate the clinical features, outcomes, and prognostic factors
      of PFTE in the largest series of cases. RESULT: Thirty-eight patients were
      included in this study. Gross total removal (GTR) of the tumors was achieved in
      33(87%) patients. Five (13%) patients had subtotal resection (STR). For the
      residual tumors, postoperative radiotherapy increased the interval between the
      first surgery and tumor regrowth (P = 0.063). Six patients had local
      recurrence/progression. Univariate analysis identified STR(P = 0.001),
      unencapsulated tumor (P = 0.018), tumor involving more than two vertebral columns
      (P = 0.005), and tumor invading sacral canal(P < 0.001) as predictors of tumor
      recurrence. In addition, 36 (95%) patients had stable or improved neurological
      status directly after surgery. Klekamp-Samii score was better correlated with the
      symptoms than McCormick scale. CONCLUSION: Extent of surgical removal, tumor
      size, tumor location, and the integrity of tumor capsule are the prognostic
      factors of PFTEs, and the intrasacral PFTEs always have a poor prognosis.

PMID- 24279507
TI  - Fe(III) reduction during pyruvate fermentation by Desulfotomaculum reducens
      strain MI-1.
AB  - Desulfotomaculum reducens MI-1 is a Gram-positive, sulfate-reducing bacterium
      also capable of reducing several metals, among which is Fe(III). Very limited
      knowledge is available on the potential mechanism(s) of metal reduction among
      Gram-positive bacteria, despite their preponderance in the microbial communities
      that inhabit some inhospitable environments (e.g., thermal or hyperthermal
      ecosystems, extreme pH or salinity environments, heavy metal or radionuclide
      contaminated sediments). Here, we show that in the presence of pyruvate, this
      micro-organism is capable of reducing both soluble Fe(III)-citrate and solid
      phase hydrous ferric oxide, although growth is sustained by pyruvate fermentation
      rather than Fe(III) respiration. Despite the fact that Fe(III) reduction does not
      support direct energy conservation, D. reducens uses it as a complementary means
      of discarding excess reducing equivalent after H2 accumulation in the culture
      headspace renders proton reduction unfavorable. Thus, Fe(III) reduction permits
      the oxidation of greater amounts of pyruvate than fermentation alone. Fe(III)
      reduction by D. reducens is mediated by a soluble electron carrier, most likely
      riboflavin. Additionally, an intracellular electron storage molecule acts as a
      capacitor and accumulates electrons during pyruvate oxidation for slow release to
      Fe(III). The reductase responsible for the transfer of electrons from the
      capacitor to the soluble carrier has not been identified, but data presented here
      argue against the involvement of c-type cytochromes. 

PMID- 24279508
TI  - Two splicing variants of a novel family of octopamine receptors with different
      signaling properties.
AB  - The octopamine and tyramine, as the invertebrate counterparts of the vertebrate
      adrenergic transmitters, control and modulate many physiological and behavioral
      processes. Both molecules mediate their effects by binding to specific receptors
      belonging to the superfamily of G-protein-coupled receptors. So far, four
      families of octopamine and tyramine receptors have been reported. Here, we
      described the functional characterization of one putative octopamine/tyramine
      receptor gene from the rice stem borer, Chilo suppressalis. By a mechanism of
      alternative splicing, this receptor gene (CsOA3) encodes two molecularly distinct
      transcripts, CsOA3S and CsOA3L. CsOA3L differs from CsOA3S on account of the
      presence of an additional 30 amino acids within the third intracellular loop.
      When heterologously expressed, both receptors cause increases of intracellular
      Ca(2+) concentration. The short form, CsOA3S, was activated by both octopamine
      and tyramine, resulting in decreased intracellular cAMP levels ([cAMP]i ) in a
      dose-dependent manner, whereas dopamine and serotonin are not effective. However,
      CsOA3L did not show any impact on [cAMP]i . Studies with series of agonists and
      antagonists confirmed that CsOA3 has a different pharmacological profile from
      that of other octopamine receptor families. The CsOA3 is, to our knowledge, a
      novel family of insect octopamine receptors.

PMID- 24279509
TI  - Radiation injury to the normal brain measured by 3D-echo-planar spectroscopic
      imaging and diffusion tensor imaging: initial experience.
AB  - BACKGROUND AND PURPOSE: Whole brain radiation therapy (WBRT) may cause cognitive
      and neuropsychological impairment and hence objective assessment of adverse
      effects of radiation may be valuable to plan therapy. The purpose of our study
      was to determine the potential of echo planar spectroscopic imaging (EPSI) and
      diffusion tensor imaging (DTI) in detecting subacute radiation induced injury to
      the normal brain. MATERIALS AND METHODS: Four patients with brain metastases and
      three patients with lung cancer underwent cranial irradiation. These patients
      were subjected to 3D-EPSI and DTI at two time points (pre-radiation, and 1 month
      post-irradiation). Parametric maps of N-acetyl aspartate (NAA), creatine (Cr),
      choline (Cho), mean diffusivity (MD), and fractional anisotropy (FA) were
      generated and co-registered to post-contrast T1-weighted images. Normal appearing
      gray-matter and white-matter regions were compared between the two time points to
      assess sub-acute effects of radiation using independent sample t-tests. RESULTS:
      Significantly increased MD (P = .02), Cho/Cr (P = .02) and a trend towards a
      decrease in NAA/Cr (P = .06) was observed from the hippocampus. Significant
      decrease in FA (P = .02) from the centrum-semiovale and a significant increase in
      MD (P = .04) and Cho/Cr (P = .02) from genu of corpus-callosum was also observed.
      CONCLUSIONS: Our preliminary findings suggest that 3D-EPSI and DTI may provide
      quantitative measures of radiation induced injury to the normal brain.

PMID- 24279510
TI  - MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting
      SphK1.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) is still a major gynecologic problem
      with poor 5 year survival rate due to distance metastases, despite routine
      surgery and chemotherapy. The precise underlying molecular mechanisms that
      trigger EOC migration and invasion are unclear. Recent studies suggest that the
      expression of microRNAs is widely dysregulated in ovarian cancer; and that they
      have evolved into tumorigenic processes, including cell proliferation, apoptosis
      and motility. METHODS: The expression of miR-124 was assessed in clinical ovarian
      cancer specimens and cell lines using miRNA qRTPCR. The function of miR-124 on
      cell migration and invasion was confirmed in vitro through wound healing assay
      and transwell assay. Luciferase reporter assay was used to confirm target
      associations. RESULTS: We showed that miR-124 is down-regulated in ovarian cancer
      specimens as well as in cell lines; and that low-level expression of miR-124 is
      much lower in highly metastatic ovarian cancer cells and tissues. Meantime,
      overexpression of miR-124 dramatically inhibits the motility of ovarian cancer
      cells in vitro and substantially suppresses the protein expression of SphK1,
      reported as an invasion and metastasis-related gene in human cancers, whose
      expression is markedly increased in both ovarian cancer cell lines and clinical
      samples, particularly in two highly metastasis cells, SKOV3-ip and HO8910pm as
      well as metastatic ovarian tumor tissues. Furthermore, SphK1 is identified as a
      direct target of miR-124, and knock-down of SphK1 in ovarian cancer cells, SKOV3
      ip and HO8910pm, could mimic the inhibition of migration and invasion by miR-124,
      while re-introduction of SphK1 abrogates the suppression of motility and
      invasiveness induced by miR-124 in both cell lines. CONCLUSIONS: Our studies
      suggest a protective role of miR-124 in inhibition of migration and invasion in
      the molecular etiology of ovarian cancer, and a potentially novel application of
      miR-124 in the regulation of migration and invasion in EOC.

PMID- 24279511
TI  - Single-port one-stage bilateral thoracoscopic sympathicotomy for severe
      hyperhidrosis: prospective analysis of a standardized approach.
AB  - BACKGROUND: Primary palmar and/or axillary focal hyperhidrosis is a frequent
      disorder characterized by excessive sweating beyond physiological needs, often
      leading to a substantial impairment of quality of life. Over the years several
      minimally invasive surgical treatments have been described, however results vary,
      and due to a lack of uniform surgical approach, technique and nomenclature are
      often difficult to compare. In this prospective study we sought to evaluate the
      safety and effectiveness of our standardized technique of single-port, one-stage
      bilateral thoracoscopic sympathicotomy. METHODS: On a prospective basis a hundred
      consecutive patients with severe or intolerable primary hyperhidrosis underwent
      one-stage bilateral single-port thoracoscopic sympathicotomy. Primary outcome was
      measured in pre- vs. post-operative Hyperhidrosis Disease Severity Scale scores.
      Location and extend of compensatory hyperhidrosis, and satisfaction with the
      procedure were registered. RESULTS: A significant reduction in mean Hyperhidrosis
      Disease Severity Scale score (3.69 +/- 0.47 preoperatively vs. 1.06 +/- 0.34
      postoperatively) (p < 0.001) was observed. In 97 (97%) out of the 100 enrolled
      patients a >80% reduction in sweat production was achieved. Compensatory
      hyperhidrosis was seen in 27 patients (27%). It was rated as mild by 21 patients
      (78%) and as moderate by 6 (22%) of these patients. No severe compensatory
      hyperhidrosis was reported. Major complications, such as intraoperative bleeding,
      infections, and Horner's syndrome were not observed. CONCLUSIONS: Highly
      selective sympathicotomy at well-defined levels with a one-stage bilateral single
      port transaxillary thoracoscopic approach is a save procedure, with excellent and
      reproducible immediate results in the treatment of primary palmar and/or axillary
      hyperhidrosis.

PMID- 24279513
TI  - Feasibility and outcome of dialogical exposure therapy for posttraumatic stress
      disorder: a pilot study with 25 outpatients.
AB  - OBJECTIVE: The research on psychotherapy for posttraumatic stress disorder (PTSD)
      stems predominantly from a cognitive-behavioral orientation while other
      approaches are underrepresented. We evaluated dialogical exposure in trauma
      therapy (DET), a treatment for PTSD combining cognitive-behavioral elements with
      an interpersonal, gestalt-based framework. METHODS: In this uncontrolled pilot
      trial, 25 PTSD patients were treated with DET in an outpatient setting and 21
      completed therapy. RESULTS: There was a significant reduction in self-rated PTSD
      symptoms from pre- to posttreatment. Effect sizes were large in the completer
      sample and moderate to large in the intent-to-treat sample. General
      psychopathology also decreased significantly. The dropout rate was rather low at
      16%. CONCLUSION: These results show that further research on DET as a treatment
      for PTSD is warranted.

PMID- 24279512
TI  - Sina and Sinb genes in triticale do not determine grain hardness contrary to
      their orthologs Pina and Pinb in wheat.
AB  - BACKGROUND: Secaloindoline a (Sina) and secaloindoline b (Sinb) genes of
      hexaploid triticale (x Triticosecale Wittmack) are orthologs of puroindoline a
      (Pina) and puroindoline b (Pinb) in hexaploid wheat (Triticum aestivum L.). It
      has already been proven that RNA interference (RNAi)-based silencing of Pina and
      Pinb genes significantly decreased the puroindoline a and puroindoline b proteins
      in wheat and essentially increased grain hardness (J Exp Bot 62:4025-4036, 2011).
      The function of Sina and Sinb in triticale was tested by means of RNAi silencing
      and compared to wheat. RESULTS: Novel Sina and Sinb alleles in wild-type plants
      of cv. Wanad were identified and their expression profiles characterized.
      Alignment with wheat Pina-D1a and Pinb-D1a alleles showed 95% and 93.3% homology
      with Sina and Sinb coding sequences. Twenty transgenic lines transformed with two
      hpRNA silencing cassettes directed to silence Sina or Sinb were obtained by the
      Agrobacterium-mediated method. A significant decrease of expression of both Sin
      genes in segregating progeny of tested T1 lines was observed independent of the
      silencing cassette used. The silencing was transmitted to the T4 kernel
      generation. The relative transcript level was reduced by up to 99% in T3 progeny
      with the mean for the sublines being around 90%. Silencing of the Sin genes
      resulted in a substantial decrease of secaloindoline a and secaloindoline b
      content. The identity of SIN peptides was confirmed by mass spectrometry. The
      hardness index, measured by the SKCS (Single Kernel Characterization System)
      method, ranged from 22 to 56 in silent lines and from 37 to 49 in the control,
      and the mean values were insignificantly lower in the silent ones, proving
      increased softness. Additionally, the mean total seed protein content of silenced
      lines was about 6% lower compared with control lines. Correlation coefficients
      between hardness and transcript level were weakly positive. CONCLUSIONS: We
      documented that RNAi-based silencing of Sin genes resulted in significant
      decrease of their transcripts and the level of both secaloindoline proteins,
      however did not affect grain hardness. The unexpected, functional differences of
      Sin genes from triticale compared with their orthologs, Pin of wheat, are
      discussed.

PMID- 24279514
TI  - Improved minicircle DNA biosynthesis for gene therapy applications.
AB  - Minicircular DNA (mcDNA) biopharmaceuticals have recently risen as a valuable
      alternative for the development of a next generation of bioactive therapeutics
      because they are more efficient and safer than standard plasmid DNA (pDNA). To
      date, the relatively insufficient knowledge regarding mcDNA biosynthesis is
      currently hindering its manufacture in suitable amounts for clinical trial
      evaluations. Addressing this limitation is therefore mandatory to bring forth the
      full therapeutic potential of this cutting-edge technology. Herein, we describe
      for the first time new processing parameters that improve the overall yield of
      mcDNA obtained from bacterial fermentations. We provide details for further in
      line monitoring and optimization in view of the current good manufacturing
      guidelines. Our results show that by rising growth temperature to 42 degrees C,
      an increase in the overall minicircle producer plasmid yield is attained, while
      biomass amounts are reduced. Moreover, by monitoring in real time the dynamic
      recombination of parental plasmids to mcDNA, we found that this event is more
      efficient at specific time points, regardless of the growth temperature and
      inductor concentration used. These are important findings since mcDNA can be
      recovered with higher yields at these determined key stages. Indeed, the
      manipulation of these parameters resulted in a 2.21-fold increase in mcDNA
      production compared with the established growth temperatures for this technology.
      Overall, our findings highlight that to achieve maximum productivity while
      attaining pharmaceutical-grade mcDNA preparations, process design and
      biosynthesis optimization must take into account key parameters such as
      temperature, inductor concentration, and recovery time.

PMID- 24279516
TI  - Inorganic/organic doped carbon aerogels as biosensing materials for the detection
      of hydrogen peroxide.
AB  - In this article, three different inorganic/organic doped carbon aerogel (CA)
      materials (Ni-CA, Pd-CA, and Ppy-CA) were, respectively, mixed with ionic liquid
      (IL) to form three stable composite films, which were used as enhanced elements
      for an integrated sensing platform to increase the surface area and to improve
      the electronic transmission rate. Subsequently, the effect of the materials
      performances such as adsorption, specific surface area and conductivity on
      electrochemistry for myoglobin (Mb) was discussed using N2 adsorption-desorption
      isotherm measurements, scanning electron microscopy (SEM), and electrochemical
      impedance spectroscopy (EIS). Moreover, they could act as sensors toward the
      detection of hydrogen peroxide (H2O2) with lower detection limits (1.68 MUM, 1.02
      MUM, and 0.85 MUM, for Ni-CA/IL/Mb-CPE, Pd-CA/IL/Mb-CPE, and Ppy-CA/IL/Mb-CPE,
      respectively) and smaller apparent Michaelis-Menten constants KM. The results
      indicated that the electroconductibility of the doped CA materials would become
      dominant, thus playing an important role in facilitating the electron transfer.
      Meanwhile, the synergetic effect with [BMIm]BF4 IL improved the capability of the
      composite inorganic/organic doped CA/IL matrix for protein immobilization. This
      work demonstrates the feasibility and the potential of a series of CA-based
      hybrid materials as biosensors, and further research and development are required
      to prepare other functional CAs and make them valuable for more extensive
      application in biosensing. 

PMID- 24279517
TI  - Open questions: a few that need answers in immunology.

PMID- 24279515
TI  - Electron flow through metalloproteins.

PMID- 24279518
TI  - Dealing with radicals.

PMID- 24279520
TI  - Among the good ideas, missed opportunities.

PMID- 24279519
TI  - KM110329 in adult patients with atopic dermatitis: a randomised, double-blind,
      placebo-controlled, multicentre trial--study protocol.
AB  - BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease with a high
      prevalence rate and a large socioeconomic cost. There are many treatments for
      atopic dermatitis, such as antihistamine, tacrolimus and corticosteroids.
      However, due to concern about the adverse effects, many patients seek alternative
      treatments. In this context, natural products are gaining interest. KM110329 is a
      functional food consisting of four herbs that are beneficial to skin health. The
      purpose of this study is to assess the efficacy and safety of KM110329 for atopic
      dermatitis. METHODS/DESIGN: This study is a randomised, double-blind, placebo
      controlled and multicentre trial of KM110329. For this study, we will recruit 66
      atopic dermatitis patients of both sexes, with ages ranging from 18 to 65, from
      three university hospitals. The participants will receive either KM110329 or a
      placebo twice a day for 8 weeks. The primary end point will be a change in the
      scoring atopic dermatitis (SCORAD) index. The secondary end points will include
      changes to the dermatology life quality index (DLQI) and transepidermal water
      loss (TEWL), among others. The outcomes will be measured at every visit. The
      study will be continued for 8 weeks and will include five visits with each
      subject (at screening and at 0, 1, 4 and 8 weeks). DISCUSSION: This trial will
      provide research methodologies for evaluate clinical efficacy and safety of
      KM110329 in adult patients with atopic dermatitis. In addition, we will evaluate
      the changes in the general skin health status and quality of life. TRIAL
      REGISTRATIONS: ClinicalTrials.gov NCT01692093.

PMID- 24279522
TI  - Hospital inspections uncover lack of staff on older people's wards.

PMID- 24279527
TI  - 'We need to ensure time to care and time to recover from caring'.

PMID- 24279531
TI  - Hunt promises 3,700 more nurses, but numbers continue to decline.

PMID- 24279536
TI  - Draft medicines guidance highlights the rights of care home residents.

PMID- 24279537
TI  - Hunt: 'A blueprint for restoring trust in the health service'.

PMID- 24279543
TI  - Osteoarthritis.

PMID- 24279544
TI  - Where health gets personal.
AB  - A major new report says that public health would benefit if policymakers did more
      to support couple, family and social relationships. Nurses working in services
      that focus on patient's relationships with their partner, family or friends
      explain how this approach is an essential part of holistic care.

PMID- 24279545
TI  - Helping to ease the pain.
AB  - Amanda Howarth won nurse of the year in 2001 for her trailblazing work helping
      patients with multiple sclerosis to manage painful symptoms. Her award raised the
      profile of the disease and its associated pain and this was important to patients
      nationwide.

PMID- 24279546
TI  - 'I love hands-on care'.
AB  - Enrolled nurse training was phased out in the UK during the 1980s, but most
      English-speaking countries retain second-level nurses and in Australia and New
      Zealand the role is flourishing. Enrolled nurses can take on a high level of
      responsibility while maintaining close contact with patients. They are an
      attractive option for employers. In the UK there seems little prospect that
      enrolled nurse will be revived.

PMID- 24279570
TI  - Care of patients with fibromyalgia: assessment and management.
AB  - Fibromyalgia is a common condition characterised by widespread musculoskeletal
      pain, muscle stiffness, unrefreshed sleep and fatigue. The condition is
      associated with several physical and psychological manifestations, including
      irritable bowel syndrome and anxiety. The efficacy of drug therapy is limited,
      therefore the nurse has an important role in providing advice and guidance on
      symptom management to optimise functioning for patients. 

PMID- 24279571
TI  - Utility and limitations of genetic/genomic information and testing.
AB  - This is the sixth article in a series exploring genetics and genomics health
      care. The focus of this article is how to apply knowledge and understanding of
      the utility and limitations of genetic and genomic information and testing to
      underpin care and support for individuals and families before, during and after
      decision making. This is essential to ensure that nurses can confidently provide
      genetics and genomics health care. 

PMID- 24279572
TI  - Improving the management of asthma in older adults.
AB  - Older people with asthma are a discrete patient group that requires specialist
      nursing skills and knowledge. They have specific and sometimes hidden needs that
      will affect their quality of life unless these are addressed by caring and
      competent nurses who have an interest in asthma. It is necessary to focus on both
      asthma and ageing to help older people achieve good asthma outcomes. This article
      discusses the complex physical, social and psychological issues affecting people
      with asthma aged 64 or older, age-related risk factors for poor control, age
      related barriers to assessment and treatment, the scope of pharmacological and
      non-pharmacological approaches, and principal treatment outcomes. Providing high
      quality services and information will equip older people to manage their asthma
      more effectively, attain physical and mental wellbeing, and lead to fewer
      hospitalisations and fatal episodes in this group. 

PMID- 24279573
TI  - Parenteral nutrition.
AB  - Parenteral nutrition is an intravenous method of providing nutrition to patients
      by delivering nutrients directly into the bloodstream via a venous access device.
      It is prescribed by a specialist nutrition support team, which may include a
      pharmacist, specialist nutrition nurse, dietician and doctor, to ensure that it
      is given appropriately and safely. 

PMID- 24279574
TI  - Reach out, build trust.

PMID- 24279576
TI  - Out of the starting blocks.
AB  - Traditionally sports medicine is the preserve of doctors and physiotherapists,
      but the 2012 London Olympics and next year's Commonwealth Games in Glasgow have
      inspired nurses to become involved. 

PMID- 24279577
TI  - In recognition of excellence.

PMID- 24279578
TI  - Student life -- being called to account.

PMID- 24279579
TI  - What to do when leak happens.

PMID- 24279580
TI  - Review article: management of chronic hepatitis C in patients with
      contraindications to anti-viral therapy.
AB  - BACKGROUND: There are patients with chronic hepatitis C who are not eligible for
      the current interferon-based therapies or refuse to be treated due to secondary
      effects. AIM: To provide information on alternative treatments for the management
      of these patients. METHODS: A PubMed search was performed to identify relevant
      literature. Search terms included hepatitis C virus, anti-inflammatory treatment,
      antioxidant, natural products and alternative treatment, alone or in combination.
      Additional publications were identified using the references cited by primary and
      review articles. RESULTS: Several approaches, such as iron depletion
      (phlebotomy), treatment with ursodeoxycholic acid or glycyrrhizin, have anti
      inflammatory and/or anti-fibrotic effects. Life interventions like weight loss,
      exercise and coffee consumption are associated with a biochemical improvement.
      Other alternatives (ribavirin monotherapy, amantadine, silibinin, vitamin
      supplementation, etc.) do not have any beneficial effect or need to be tested in
      larger clinical studies. CONCLUSION: There are therapeutic strategies and
      lifestyle interventions that can be used to improve liver damage in patients with
      chronic hepatitis C who cannot receive or refuse interferon-based treatments.

PMID- 24279581
TI  - Bioavailability enhancement of ondansetron after nasal administration of
      Caesalpinia pulcherrima-based microspheres.
AB  - CONTEXT: Natural polymers have attracted a great deal of attention for use as
      potential carriers in site-specific delivery over past decades. Mucoadhesive
      microspheres are useful tools for nasal drug delivery. OBJECTIVES: To prepare and
      evaluate mucoadhesive microspheres as mode for nasal delivery of ondansetron
      using Caesalpinia pulcherrima galactomannan (CPG). MATERIALS AND METHODS:
      Conventional spray-dried CPG nasal microspheres loaded with ondansetron for
      intranasal drug delivery in order to avoid the first pass metabolism with
      improved therapeutic efficiency in treatment of nausea and vomiting as an
      alternative therapy to parenterals. Developed microspheres were evaluated for
      characteristics like particle size, entrapment efficiency, zeta potential,
      swelling ability, in-vitro mucoadhesion, in-vitro drug release, DSC, XRD study
      and histopathological evaluation of tissue. CPG-based ondansetron microspheres
      were studied in rabbits for screening nasal absorption potential of nasal
      formulation. RESULTS: Developed nasal microspheres possess entrapment efficiency
      of 80-89%, higher mucoadhesion of 72-84% across goat nasal mucosa. In-vivo study
      showed that microspheres based on mucoadhesive polymer were able to promote quick
      drug absorption as well as enhanced bioavailability of drug. DISCUSSION:
      Histopathological studies evaluated biocompatible and nontoxic nature of CPG in
      nasal cavity. Developed mucoadhesive microspheres by nasal route showed
      enhancement of bioavailability as compared to oral route in rabbits. CONCLUSION:
      CPG-based mucoadhesive microspheres can successfully deliver ondansetron
      intranasally, sustain its effect, avoid first pass effect, an alternative route
      of administration to injection and thus enhance systemic bioavailability of
      ondansetron hydrochloride.

PMID- 24279583
TI  - Two novel KIR3DL1 alleles, 3DL1*0150205 and 3DL1*0150206, identified by full
      length DNA sequencing.
AB  - KIR3DL1*0150205 and KIR3DL1*0150206 alleles have five and six mutations,
      respectively, compared with KIR3DL1*0150201. 

PMID- 24279584
TI  - A Critical Review about Human Exposure to Polychlorinated Dibenzo-p-Dioxins
      (PCDDs), Polychlorinated Dibenzofurans (PCDFs) and Polychlorinated Biphenyls
      (PCBs) through Foods.
AB  - Dioxins include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and part of polychlorinated biphenyls (PCBs). Only the
      compounds that are chlorinated at the 2,3,7, and 8 positions have characteristic
      dioxin toxicity. PCDDs, PCDFs and PCBs accumulate in the food chain due to their
      high lipophilicity, high stability, and low vapor pressure. They are not
      metabolized easily; however their hydroxylated metabolites are detected in feces.
      They cause a wide range of endocrine disrupting effects in experimental animals,
      wildlife, and humans. Endocrine related effects of PCDDs, PCDFs and PCBs on
      thyroid hormones, neurodevelopment and reproductive development were referenced.
      In addition, some studies of contamination of foods, bioaccumulation, dietary
      exposure assessment, as well as challenges of scientific research in these
      compounds were reviewed. 

PMID- 24279585
TI  - Estrogen and androgen receptor expression in surface epithelium and inclusion
      cyst in the ovary of premenopausal and postmenopausal women.
AB  - BACKGROUND: The importance of surface epithelium and epithelial inclusion cysts
      in the ovary arises from studies demonstrating that these structures are
      susceptible to epithelial ovarian cancer development. The expression of estrogen
      receptor alpha (ER alpha), androgen receptor (AR), in epithelial cells of the
      ovary from premenopausal and postmenopausal women is interesting because sexual
      steroid hormones are involved in cell growth and differentiation. METHODS: The
      presence of ER alpha, AR, and the orphan G protein-coupled receptor 30 (GPR30)
      was demonstrated by immunofluorescence in ovaries obtained from 79 pre and
      postmenopausal patients, undergoing histero-salpingo-oophorectomy for
      proliferative gynecological diseases. The proportion of patients that displayed
      positive reaction for estrogen and androgen receptors in epithelial cells of the
      ovary was evaluated according to menopausal status and associated pathology.
      RESULTS: The proportion of patients that displayed a positive receptor expression
      in the epithelial cells of the ovarian surface and cortical inclusion cysts shows
      that ER alpha is present in 20 of 79 patients (0.25), AR in 33 of 79 (0.42) and
      GPR30 in 38 of 55 (0.69). There are no differences in ER alpha, AR, and GPR30
      expression between pre and postmenopausal patients and considering the associated
      pathology, proportions for ER alpha and GPR30 are similar. The patients with
      cervical cancer show a higher proportion of AR expression in epithelial cells of
      the ovary, which is statistically significant (P < 0.01) compared with patients
      with other proliferative diseases. CONCLUSIONS: The presence of ER alpha, AR, and
      GPR30 in the surface epithelial ovarian cells and its derivatives are observed
      with a proportion that is specific for each receptor. The proportion of
      expression for these receptors in the epithelial cells of the ovary does not
      change after menopause. The proportion of ovaries with AR positive epithelial
      cells in patients with cervical squamous carcinoma is higher compared with other
      gynecological pathologies.

PMID- 24279586
TI  - Characterization of polyethylene glycol-polyethyleneimine as a vector for alpha
      synuclein siRNA delivery to PC12 cells for Parkinson's disease.
AB  - AIMS: Gene therapy targeting the SNCA gene yields promising results in the
      treatment of Parkinson's disease (PD). The most challenging issue of the RNAi
      gene therapy strategy is maintaining efficient delivery without inducing
      significant toxicity and other adverse effects. This study aimed to characterize
      polyethylene glycol-polyethyleneimine as a vector for alpha-synuclein siRNA
      delivery to PC12 cells for Parkinson's disease. METHODS: The characteristics of
      PEG-PEI/siSNCA were analyzed via gel retardation assay and assessments of
      particle size and zeta potential. MTT cytotoxicity assay and flow cytometry were
      used to detect cytotoxicity and transfection efficiency in PC12 cells. Confocal
      laser scanning microscopy was employed to examine the intracellular distribution
      of PEG-PEI/FITC-siSNCA after cellular uptake. RT-PCR and western blotting were
      used to measure SNCA expression. The MTT cytotoxicity assay was used to study the
      effect of PEG-PEI/siSNCA on cell viability. The protective effect of PEG
      PEI/siSNCA on MPP+-induced apoptosis in PC12 cells was examined via flow
      cytometry and Hoechst staining. RESULTS: PEG-PEI/siSNCA complexes were well
      developed; they exhibited appropriate particle sizes and zeta potentials at a
      mass ratio of 5:1. In vitro, PEG-PEI/siSNCA was associated with low cytotoxicity
      and high transfection efficiency. Complexes were capable of successfully
      delivering siSNCA into PC12 cells and releasing it from the endosome.
      Furthermore, PEG-PEI/siSNCA could effectively suppress SNCA mRNA expression and
      protected cells from death via apoptosis induced by MPP(+) . CONCLUSIONS: Our
      results demonstrate that PEG-PEI performs well as a vector for alpha-synuclein
      siRNA delivery into PC12 cells. Additionally, PEG-PEI/siSNCA complexes were
      suggested to be able to protect cells from death via apoptosis induced by MPP(+)
      . These findings suggest that PEG-PEI/siSNCA nanoparticles exhibit remarkable
      potential as a gene delivery system for Parkinson's disease.

PMID- 24279587
TI  - Why is mucormycosis more difficult to cure than more common mycoses?
AB  - Although considered to be a rare infection, mucormycosis (zygomycosis) has
      emerged as the second most common invasive mould infection. Despite the advent of
      newer antifungal agents, mortality rate of mucormycosis remains exceedingly high.
      Successful management of mucormycosis requires early diagnosis, reversal of
      underlying predisposing risk factors, surgical debridement and prompt
      administration of active antifungal agents. However, mucormycosis is not always
      amenable to cure. There are challenging obstacles that lead to difficulties in
      management of amphotericin B. These include unique host-based risk factors for
      mucormycosis, the fungus' resistance to innate host defences and distinctive
      features of its immunopathogenesis, such as extensive angioinvasion, increased
      virulence and use of chelators by the fungus as siderophores. In addition to
      these obstacles, the difficulties in early diagnosis, including nonspecific
      clinical manifestations, lack of serological methods, as well limitations of
      culture and molecular methods, lead to delay in initiation of antifungal therapy.
      Finally, the variability of susceptibility to amphotericin B and resistance to
      most other conventional antifungal agents leads to major limitations in
      successful treatment of this devastating infection.

PMID- 24279588
TI  - Risk factors for impaired CD4+ T-cell reconstitution following rabbit
      antithymocyte globulin treatment in kidney transplantation.
AB  - To describe long-term CD4+ T-cell reconstitution after rabbit antithymocyte
      globulin (rATG) treatment and identify predictive factors following kidney
      transplantation. A single-center retrospective study analyzed lymphocyte subsets
      in rATG-treated kidney transplant recipients (1986-2009). 589 patients were
      analyzed (maximum follow-up 21 years). A comparator group (n=298) received an
      anti-IL-2 receptor monoclonal antibody. CD4+ T-cell lymphopenia (<200/mm3) was
      present in 48.5%, 9.2%, 6.7%,2.0%, and 0% of patients at one, three, five, 10,
      and 20 years post-transplant, respectively. CD4+ T-cell count increased during
      the first 10 years but remained below the pretransplant count even after 20
      years. At 1, 3, and 6 months post-transplant, mean CD4+ T-cell count was
      significantly lower in patients with CD4+ T-cell lymphopenia at 12 months versus
      patients without lymphopenia. On multivariate analyses, significant independent
      predictors for long-term impaired CD4 T-cell reconstitution were recipient age,
      pretransplant CD4+ T-cell count, 12-month CD4+ T-cell count, and tacrolimus or
      MMF therapy. Recipient age>40 years was identified as a cutoff point. CD4+ T-cell
      reconstitution following rATG treatment remains impaired even after 21 years.
      Most risk factors for long-term impaired CD4+ T-cell reconstitution may be
      evaluated pretransplant or are modifiable post-transplant.

PMID- 24279589
TI  - Interface dynamics explain assembly dependency of influenza neuraminidase
      catalytic activity.
AB  - Influenza virus neuraminidase (iNA) is a homotetrameric surface protein of the
      influenza virus and an established target for antiviral drugs. In contrast to
      neuraminidases (NAs) of other biological systems (non-iNAs), enzymatic activity
      of iNA is only observed in a quaternary assembly and iNA needs the
      tetramerization to mediate enzymatic activity. Obviously, differences on a
      molecular level between iNA and non-iNAs are responsible for this intriguing
      observation. Comparison between protein structures and multiple sequence
      alignment allow the identification of differences in amino acid composition in
      crucial regions of the enzyme, such as next to the conserved D151 and the 150
      loop. These differences in amino acid sequence and protein tetramerization are
      likely to alter the dynamics of the system. Therefore, we performed molecular
      dynamics simulations to investigate differences in the molecular flexibility of
      monomers, dimers, and tetramers of iNAs of subtype N1 (avian 2004, pandemic 1918
      and pandemic 2009 iNA) and as comparison the non-iNA monomer from Clostridium
      perfringens. We show that conformational transitions of iNA are crucially
      influenced by its assembly state. The protein-protein interface induces a complex
      hydrogen-bonding network between the 110-helix and the 150-loop, which
      consequently stabilizes the structural arrangement of the binding site.
      Therefore, we claim that these altered dynamics are responsible for the
      dependence of iNA's catalytic activity on the tetrameric assembly. Only the
      tetramerization-induced balance between stabilization and altered local
      flexibility in the binding site provides the appropriate arrangement of key
      residues for iNA's catalytic activity. 

PMID- 24279590
TI  - Recognition of depression and anxiety and their association with quality of life,
      hospitalization and mortality in primary care patients with heart failure - study
      protocol of a longitudinal observation study.
AB  - BACKGROUND: International disease management guidelines recommend the regular
      assessment of depression and anxiety in heart failure patients. Currently there
      is little data on the effect of screening for depression and anxiety on the
      quality of life and the prognosis of heart failure (HF). We will investigate the
      association between the recognition of current depression/anxiety by the general
      practitioner (GP) and the quality of life and the patients' prognosis.
      METHODS/DESIGN: In this multicenter, prospective, observational study 3,950
      patients with HF are recruited by general practices in Germany. The patients fill
      out questionnaires at baseline and 12-month follow-up. At baseline the GPs are
      interviewed regarding the somatic and psychological comorbidities of their
      patients. During the follow-up assessment, data on hospitalization and mortality
      are provided by the general practice. Based on baseline data, the patients are
      allocated into three observation groups: HF patients with depression and/or
      anxiety recognized by their GP (P+/+), those with depression and/or anxiety not
      recognized (P+/-) and patients without depression and/or anxiety (P-/-). We will
      perform multivariate regression models to investigate the influence of the
      recognition of depression and/or anxiety on quality of life at 12 month follow
      up, as well as its influences on the prognosis (hospital admission, mortality).
      DISCUSSION: We will display the frequency of GP-acknowledged depression and
      anxiety and the frequency of installed therapeutic strategies. We will also
      describe the frequency of depression and anxiety missed by the GP and the
      resulting treatment gap. Effects of correctly acknowledged and missed
      depression/anxiety on outcome, also in comparison to the outcome of subjects
      without depression/anxiety will be addressed. In case results suggest a treatment
      gap of depression/anxiety in patients with HF, the results of this study will
      provide methodological advice for the efficient planning of further
      interventional research.

PMID- 24279591
TI  - Identification of a novel HIV Type 1 circulating recombinant form (CRF65_cpx)
      composed of CRF01_AE and subtypes B and C in Western Yunnan, China.
AB  - A novel HIV-1 circulating recombinant form (CRF) designated CRF65_cpx was
      recently characterized from three epidemiologically unlinked individuals infected
      through heterosexual contact in western Yunnan province of China. This is the
      first complex mosaic HIV-1 CRF, consisting of contributions from three or more
      different subtypes, identified in China. An additional full-length genome
      sequence with identical recombinant breakpoints was found among a previously
      reported recombinant strain from a man who had sex with a man in Anhui province
      of East Central China. The breakpoint analysis of the recombinants showed a
      complex genome organization composed of parental subtypes B' (Thailand variant of
      subtype B), C, and CRF01_AE, with 13 recombination breakpoints observed in almost
      all structure genes of HIV-1. The generation of complex recombinant forms is
      likely due to cocirculation of multiple lineages of HIV-1 strains in high-risk
      populations in western Yunnan.

PMID- 24279592
TI  - Effects of thoracic epidural analgesia on plasma cAMP and cGMP levels in patients
      with heart failure.
AB  - BACKGROUND AND AIM: The progression of heart failure is affected by several
      factors, including chronic stimulation of the beta-adrenoceptor. This clinical
      study was designed to measure the effects of thoracic epidural analgesia (TEA) on
      the plasma levels of norepinephrine (NE), cAMP, and cGMP in patients with heart
      failure and assess the clinical implication of TEA. METHODS: Forty patients with
      heart failure were randomly assigned to TEA (TEA plus standard care) and control
      groups (standard care). The plasma concentrations of cAMP, cGMP, brain
      natriuretic peptide (BNP), and NE were measured using ELISA before treatment, the
      second and fourth weeks of treatment. RESULTS: The plasma concentrations of cAMP,
      cGMP, BNP, and NE in the TEA group were significantly reduced by the fourth week
      compared to their initial concentrations (P < 0.01, for all parameters) and the
      control group (P < 0.05, P < 0.05, P < 0.01, and P < 0.05, respectively). The
      values for left ventricular end diastolic diameter (LVEDD), ejection fraction
      (EF), and fractional shortening (FS) in the TEA group improved significantly
      compared to their initial values and the control group. However, the changes in
      levels for these indices in the control group were no statistical significant
      compared to the initial levels. CONCLUSIONS: TEA can effectively decrease the
      plasma concentrations of cAMP and cGMP and improve cardiac function in patients
      with heart failure. The decreased levels of NE and cAMP occurred before the
      improvement in cardiac function, indicating that the abnormal epidural signal
      transduction can be corrected in patients with heart failure.

PMID- 24279593
TI  - Practice research network in a psychology training clinic: building an
      infrastructure to foster early attachment to the scientific-practitioner model.
AB  - Learning how to conduct clinically meaningful and actionable research while
      simultaneously training to be a competent clinician may be an optimal way to
      develop an early attachment to the scientific-practitioner model. In this paper,
      the transformation of a training clinic into a practice research network (PRN) is
      presented as a strategy to foster a seamless integration of clinical, training,
      and research facets of graduate training in psychology. With the hope of
      providing helpful guidance to trainers and trainees interested in building such
      an infrastructure, the authors describe the context in which they developed their
      training clinic PRN, its major components, and some of the studies that have been
      conducted in this network. Benefits earned and lessons learned (in terms of
      obstacles faced and strategies implemented to deal with them) are described, as
      well as general recommendations and future directions regarding the
      implementation and impact of training clinic PRNs.

PMID- 24279594
TI  - Efficacy and safety of a combined oral contraceptive containing estradiol
      valerate/dienogest: results from a clinical study conducted in North America.
AB  - BACKGROUND: This study investigated the efficacy and safety of a combined oral
      contraceptive (COC) containing estradiol valerate/dienogest (E2V/DNG). METHODS:
      This was a multicenter, noncomparative, 13-cycle (extended to 28 cycles) study
      conducted in the United States and Canada. Contraceptive efficacy was calculated
      as a Pearl Index for 13 cycles, based on all on-treatment pregnancies; bleeding
      patterns were calculated based on bleeding and spotting information recorded
      daily in diary cards. Safety events during a 16-month extension study were added
      to the 1-year data. RESULTS: In total, 499 women, aged 18-35 years, were
      enrolled, and 490 of them were included in the full analysis set for
      contraceptive efficacy. Five pregnancies occurred in the first year (unadjusted
      Pearl Index=1.64). In cycles 1-12, an average 23.5% of women had absent scheduled
      (withdrawal) bleeding. Among women with scheduled (withdrawal) bleeding, bleeding
      started after a median of 2 days after intake of the last DNG-containing pill.
      For safety, data included from 147 women followed over an additional 16 months
      were added to the original 13-cycle data set. Treatment-related adverse events
      (AEs) occurred in 51.8% of women; 14.9% discontinued because of AEs over the
      entire 28-month study period. CONCLUSION: A COC with E2V and DNG was shown to
      provide effective contraception in women aged 18-35 years in North America.

PMID- 24279595
TI  - Outcome following liver lobectomy using thoracoabdominal staplers in cats.
AB  - OBJECTIVES: To present outcomes and complications following liver lobectomy using
      thoracoabdominal staplers in cats, to identify factors associated with survival
      time and to confirm safety and feasibility. METHODS: Retrospective analysis of
      case records (n=18) of cats that underwent liver lobectomy with a
      thoracoabdominal stapler. RESULTS: Fourteen of the 18 cats (78%) survived to
      discharge. Median survival time was 136.5 days. On log-rank univariate analysis,
      preoperative abdominal fluid (P=0.002), preoperative anaemia (P=0.03) and
      perioperative transfusion (P=0.01) were associated with decreased survival time.
      Perioperative anaemia was common (89%), and rate of transfusion during
      hospitalisation was 61%. Clinical signs of illness, azotaemia, elevated liver
      enzyme activities and malignant neoplasia did not appear to impact survival;
      however, anaemia, abdominal fluid and transfusion may be associated with
      decreased survival time. CLINICAL SIGNIFICANCE: Liver lobectomy using
      thoracoabdominal staplers was effective in removal of hepatic lesions and all
      cats survived surgery. Outcome was negatively associated with preoperative
      abdominal fluid (haemorrhagic and non-haemorrhagic), preoperative anaemia or
      perioperative transfusion. Surgeons should be prepared to employ ancillary
      methods of haemostasis to augment the staple line, and need for blood transfusion
      should be anticipated.

PMID- 24279596
TI  - MALDI MS and ICP MS detection of a single CE separation record: a tool for
      metalloproteomics.
AB  - In this work, a novel approach based on off-line coupling of a single run of
      capillary electrophoresis (CE) separation to both matrix-assisted laser
      desorption/ionization (MALDI) and substrate-assisted laser desorption inductively
      coupled plasma (SALD ICP) mass spectrometry (MS) is presented. Using a liquid
      junction and subatmospheric deposition chamber, CE fractions were extracted from
      a separation capillary and collected as 20-nL droplets on a custom-built
      polyethylene terephthalate glycol (PETG) target plate coated with a 10-nm gold
      layer which guaranteed compatibility with both MALDI and SALD ICP techniques. The
      MALDI matrix solution was then added to the produced spots. After it was dried,
      the separation record was consecutively analyzed in MALDI MS and ICP MS
      instruments. Thus, both proteomic and metallomic information was obtained off
      line from a single CE run. The concept was demonstrated by the analysis of a
      mixture of rabbit liver metallothionein isoforms. In an additional study, the
      droplets representing the archived separation record were alternately mixed with
      two different MALDI matrices to obtain complementary information on both the
      apoproteins and their complexes with metals from a single separation run. The
      presented technique is a viable alternative to online coupling of column
      separation to electrospray MS and nebulizer ICP MS. 

PMID- 24279597
TI  - Physical activity monitoring in stroke: SenseWear Pro2 activity accelerometer
      versus Yamax Digi-Walker SW-200 pedometer.
AB  - PURPOSE: Determine validity and reliability of SenseWear Pro2 Armband (SWP2A) and
      Yamax Digi-Walker SW-200 Pedometer (YDWP) in stroke and healthy adults. METHODS:
      Fifteen stroke patients and 15 healthy participants wore SWP2A on upper arm and
      YDWP at hip/knee. Different activities were performed: treadmill walking, walking
      up/down a step, cycling and walking on an even surface. Steps and Energy
      Expenditure (EE) were measured and compared to steps counted manually and
      indirect calorimetry. Repeated measurements were compared to determine
      reliability of both devices. RESULTS: Spearman correlation coefficients between
      knee-worn YDWP and counted steps while walking on an even surface was >=0.89 in
      healthy and >=0.95 in stroke. Treadmill walking revealed high Spearman
      correlation coefficients in healthy individuals (rs >= 0.90) and at 1.5 km/h in
      stroke (rs = 0.69). During other activities YDWP often underestimated steps.
      SWP2A data revealed inconsistent results in EE and steps. Reliability tested by
      repeated measurements varied between 0.66 and 0.98 for YDWP and 0.61 and 0.97 for
      SWP2A. CONCLUSION: YDWP and SWP2A are both reliable. Only knee-worn YDWP is a
      valid device to measure steps except high intensity walking in stroke. YDWP
      systematically undercounts steps during other activities of short duration. This
      study could not demonstrate valid measurement of steps/EE in stroke using SWP2A.
      Implications for Rehabilitation Stroke is a disabling disease with residual
      neurologic deficits, which impairs mobility and predisposes them to sedentary
      behavior. A Yamax Digi-Walker SW-200 knee-worn pedometer showed to be a valid and
      reliable technique to measure ambulatory activity in stroke. A valid instrument
      to measure energy expenditure in stroke needs to be explored.

PMID- 24279598
TI  - Dietary intakes and risk of lymphoid and myeloid leukemia in the European
      Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - The etiology of leukemias cannot entirely be explained by known risk factors,
      including ionizing radiation, benzene exposure, and infection with human T cell
      leukemia virus. A number of studies suggested that diet influences the risk of
      adult leukemias. However, results have been largely inconsistent. We examined the
      potential association between dietary factors and risk of leukemias among
      participants of the European Prospective Investigation into Cancer and Nutrition
      study. Among the 477,325 participants with mean follow-up of 11.34 yr (SD =
      2.47), 773 leukemias (373 and 342 cases of lymphoid and myeloid leukemia,
      respectively) were identified. Diet over the previous 12 mo was assessed at
      baseline using a validated country-specific dietary questionnaire. Cox
      proportional hazards regression was used to explore the association between
      dietary factors that have previously been associated with leukemia risk,
      including red and processed meat, poultry, offal, fish, dairy products,
      vegetables, fruits, and seeds/nuts, and risk of both lymphoid and myeloid
      leukemias. No significant associations were observed between dietary measures and
      total, lymphoid, and myeloid leukemias. Additional subtype analyses showed no
      dietary association with risk of major subtypes of leukemias. In summary, this
      study did not support a possible link between selected dietary factors and risk
      of leukemias. 

PMID- 24279599
TI  - Longitudinal associations between walking frequency and depressive symptoms in
      older adults: results from the VoisiNuAge study.
AB  - BACKGROUND: Cross-sectional studies show that walking is associated with
      depression among older adults, but longitudinal associations have rarely been
      examined. The aim of this study was to investigate longitudinal associations
      between walking frequency and depressive symptoms in older adults to determine
      which variable is the stronger prospective predictor of the other. DESIGN:
      Longitudinal; four repeated measures over 5 years. SETTING: Population-based
      sample of urban-dwelling older adults living in the Montreal metropolitan area.
      PARTICIPANTS: Participants from the VoisiNuAge study aged 68 to 84 (N=498).
      MEASUREMENTS:  MAIN EXPOSURES: depressive symptoms (Geriatric Depression Scale)
      and number of walking days in previous week (Physical Activity Scale for the
      Elderly). Covariates: age, education, and number of chronic illnesses. Cross
      lagged panel analyses were performed in the entire sample and in sex-stratified
      subsamples. RESULTS: Depressive symptoms predicted walking frequency at
      subsequent time points (and more precisely, higher depressive symptoms were
      related to fewer walking days), but walking frequency did not predict depressive
      symptoms at subsequent time points. Stratified analyses revealed that prospective
      associations were statistically significant in women but not men. CONCLUSION: The
      longitudinal association between walking frequency and depressive symptoms is one
      in which depressive symptoms predict reduced walking frequency later. Higher
      depressive symptoms are more likely a cause of reduced walking because of time
      precedence than vice versa. Future research on longitudinal relationships between
      meeting physical activity recommendations and depression are warranted.

PMID- 24279600
TI  - Strong nucleosomes of A. thaliana concentrate in centromere regions.
AB  - Earlier identified strongest nucleosome DNA sequences of A. thaliana, those with
      visible 10-11 base sequence periodicity, are mapped along chromosomes. Resulting
      positional distributions reveal distinct maxima, one per chromosome, located in
      the centromere regions. Sequence-directed nucleosome mapping demonstrates that
      the strong nucleosomes (SNs) make tight arrays, several 'parallel' nucleosomes
      each, suggesting a columnar chromatin structure. The SNs represent a new class of
      centromeric nucleosomes, presumably, participating in synapsis of chromatids and
      securing the centromere architecture. 

PMID- 24279601
TI  - Contribution of molecular diagnosis to the management of cutaneous leishmaniasis
      in travellers.
AB  - Cutaneous leishmaniasis is one of the most frequent skin diseases occurring after
      travelling in endemic areas. Optimal management requires identification of the
      species of Leishmania involved. In this study we aimed to evaluate the use of
      molecular diagnosis as routine, in comparison with direct examination and
      culture. Thirty positive diagnoses were carried out between 2007 and 2013.
      Classical PCR enabled 11 positive cases to be identified that were found to be
      negative by conventional methods. Sequencing led to the identification of eight
      different species. Routine use of PCR and sequencing appears very efficient in
      the management of cutaneous leishmaniasis. 

PMID- 24279602
TI  - Evaluating complications during intraoral administration of local anesthetics in
      a rural, portable special needs dental clinic.
AB  - The aim of this study was to identify and quantify complications with local
      anesthetic administration on consecutive patients seen for dental care in a
      portable dental clinic providing care to patients with special needs. This
      prospective study includes data on the patients seen by the portable dental team.
      A standardized form is used to determine complications and associated information
      for 172 dental visits in which local anesthetic is administered. After
      statistical analysis of 172 consecutive cases, the overall complication rate is
      8.1%. All of the complications are considered to be mild or moderate; there are
      no reports of severe events. The complications encountered most frequently are
      associated with self-inflicted soft tissue injury or inadequate anesthesia.
      Comprehensive care with local anesthesia delivered by a portable dental clinic
      has a low risk of complication. The administration of an inferior alveolar nerve
      block or body-mass status appears to affect the incidence of complications. 

PMID- 24279603
TI  - Meserine, a novel carbamate AChE inhibitor, ameliorates scopolamine-induced
      dementia and alleviates amyloidogenesis of APP/PS1 transgenic mice.
AB  - AIMS: To investigate whether Meserine, a novel phenylcarbamate derivative of (-)
      meptazinol, possesses beneficial activities against cholinergic deficiency and
      amyloidogenesis, the two major pathological characteristics of Alzheimer's
      disease (AD). METHODS: Ellman's assay and Morris water maze were used to detect
      acetylcholinesterase (AChE) activity and evaluate spatial learning and memory
      ability, respectively. Both high content screening and Western blotting were
      carried out to detect beta-amyloid precursor protein (APP), while RT-PCR and
      ELISA were conducted to detect APP-mRNA and beta-amyloid peptide (Abeta).
      RESULTS: In scopolamine-induced dementia mice, Meserine (1 mg/kg, i.p.)
      significantly ameliorated spatial learning and memory deficits, which was
      consistent with its in vitro inhibitory ability against AChE (recombinant human
      AChE, IC50 = 274 +/- 49 nM). Furthermore, Meserine (7.5 mg/kg) injected
      intraperitoneally once daily for 3 weeks lowered APP level by 28% and Abeta42
      level by 42% in APP/PS1 transgenic mouse cerebrum. This APP modulation action
      might be posttranscriptional, as Meserine reduced APP by about 30% in SH-SY5Y
      APP695 cells but did not alter APP-mRNA level. And both APP and Abeta42 lowering
      action of Meserine maintained longer than that of rivastigmine. CONCLUSION:
      Meserine executes dual actions against cholinergic deficiency and amyloidogenesis
      and provides a promising lead compound for symptomatic and modifying therapy of
      AD.

PMID- 24279604
TI  - Acute adverse events from over-the-counter Chinese herbal medicines: a population
      based survey of Hong Kong Chinese.
AB  - BACKGROUND: Although over-the-counter traditional Chinese herbal medicine (COTC)
      is commonly used to treat everyday illness in many parts of the world, no
      population-based study has been done to examine the prevalence and factors
      associated with COTC-related adverse events. METHODS: A cross-sectional telephone
      survey was conducted among Hong Kong Chinese adults in 2011 (n = 1100) with
      informed verbal consent. Stepwise logistic regression of demographic, attitudinal
      and behavioral variables was used to determine factors associated with past-year
      adverse events. RESULTS: Of study respondents, 71.7% (789/1100) reported past
      year COTC use and 2.3% (25/1100) reported at least one COTC-related adverse event
      in the past year. Of the 27 adverse events cases reported among COTC users, the
      most common were allergic reactions (n = 11) dizziness (n = 5), and gastro
      intestinal problems (n = 4). Pills/capsules were the dosage form that caused the
      highest proportion of adverse events (n = 10), followed by plasters (n = 7),
      creams/ointments (n = 5), and ingestible powders (n = 2).Although COTC users
      reporting adverse events were more likely to report greater practices to avoid
      adverse events (OR = 6.47; 95% CI: 1.38-30.3); they were also more likely to
      possess lower education levels (OR = 9.64, 95% CI: 2.20-42.3) and to have
      received COTC information from non-reliable, mass-media information sources such
      as magazines (OR = 3.32; 95% CI: 1.01-8.50) or television (OR = 2.93; 95% CI:
      1.03-10.7). Package labels were also felt to be unclear by 42.9% of COTC users. A
      large proportion of COTC users demonstrated low levels of COTC-related knowledge,
      while the main impediment to greater information-seeking was the belief that
      reliable COTC information is not obtainable from Western health professionals.
      CONCLUSIONS: Despite global movements toward more stringent complementary
      medicine regulation, the limited accessibility of reliable information and
      widespread misperceptions among consumers present major challenges for the safe
      use of complementary medicine.

PMID- 24279605
TI  - Clinical relevance of the de novo production of anti-HLA antibodies following
      intestinal and multivisceral transplantation.
AB  - Despite a negative pretransplant cross-match, intestinal transplant recipients
      can mount humoral immune responses soon after transplantation. Moreover, the
      development of donor-specific anti-HLA antibodies (DSAs) is associated with
      severe graft injury. Between June 2000 and August 2011, 30 patients (median age
      37.6+/-9.8 years) received isolated intestinal transplantations (ITX, n=18) or
      multivisceral transplantations (MVTXs, n=12) at our center. We screened for human
      leukocyte antigen (HLA) antibodies pre- and post-transplant. If patients produced
      DSAs, treatment with plasmapheresis and intravenous immunoglobulin (IVIG) was
      initiated. In the event of DSA persistence and/or treatment-refractory rejection,
      rituximab and/or bortezomib were added. Ten patients developed DSAs and
      simultaneously showed significant signs of rejection. These patients received
      plasmapheresis and IVIG. Eight patients additionally received rituximab, and two
      patients were treated with bortezomib. DSA values decreased upon antirejection
      therapy in 8 of the 10 patients. The development of DSAs following ITX is often
      associated with acute rejection. We observed that the number of mismatched
      antigens and epitopes correlates with the probability of developing de novo DSAs.
      Early diagnosis and therapy, including B-cell depletion and plasma cell
      inhibition, are crucial to preventing further graft injury.

PMID- 24279607
TI  - Long-term clinical results on the use of platelet concentrate in the treatment of
      intrabony periodontal defects.
AB  - OBJECTIVE: The purpose of this clinical investigation was to evaluate long-term
      results obtained with the combination of platelet pellet (PP) plus bioabsorbable
      barrier membrane (BM) and to compare this outcome with the results obtained using
      bioactive glass (BG) graft material with a BM. MATERIALS AND METHODS: Using a
      split mouth design, 11 chronic periodontitis patients (power >= at least 80%)
      were randomly assigned to treatment with a combination of PP/GTR or BG/GTR in
      contra-lateral dentition areas. Clinical attachment level (CAL) as the primary
      outcome variable, calculated as the sum of probing pocket depth (PPD) and
      gingival recession, and radiological alveolar bone level were recorded at
      baseline, 6 months and 5 years. RESULTS: There were no statistical differences
      between test and control defects at baseline. PPD reductions and CAL and
      radiological alveolar bone height gains were statistically significant between
      baseline and 6 months and between baseline and 5 years in both groups (p < 0.01).
      Six months results of frequency distribution showed that 82% of the defects
      attained >= 4 mm CAL gain in both groups, while 5 year results showed that 73% of
      the defects attained 2 mm <= CAL gain < 4 mm in the PP/BM group and 55% of the
      defects attained 2 mm <= CAL gain < 4 mm in the BG/BM group. All parameters
      evaluated showed no significant differences between 6 months and 5 years in both
      groups (p > 0.05). No statistically significant difference in any of the clinical
      parameters was observed at 6 months and 5 years between the groups (p > 0.05).
      CONCLUSIONS: The long-term efficacy of platelet concentrate combined with a
      barrier membrane is similar with the combination of bioactive glass graft
      material and barrier membrane, suggesting that results obtained with both
      treatment approaches can be maintained over a period of 5 years.

PMID- 24279606
TI  - Activation of the inflammatory transcription factor nuclear factor interleukin-6
      during inflammatory and psychological stress in the brain.
AB  - BACKGROUND: The transcription factor nuclear factor interleukin 6 (NF-IL6) is
      known to be activated by various inflammatory stimuli in the brain.
      Interestingly, we recently detected NF-IL6-activation within the hypothalamus
      pituitary-adrenal (HPA)-axis of rats after systemic lipopolysaccharide (LPS)
      injection. Thus, the aim of the present study was to investigate whether NF-IL6
      is activated during either, inflammatory, or psychological stress in the rat
      brain. METHODS: Rats were challenged with either the inflammatory stimulus LPS
      (100 MUg/kg, i.p.) or exposed to a novel environment. Core body temperature (Tb)
      and motor activity were monitored using telemetry, animals were killed at
      different time points, brains and blood removed, and primary cell cultures of the
      anterior pituitary lobe (AL) were investigated. Analyses were performed using
      immunohistochemistry, RT-PCR, and cytokine-specific bioassays. RESULTS: Stress
      stimulation by a novel environment increased NF-IL6-immunoreactivity (IR) in the
      pituitary's perivascular macrophages and hypothalamic paraventricular cells and a
      rise in Tb lasting approximately 2 h. LPS stimulation lead to NF-IL6-IR in
      several additional cell types including ACTH-IR-positive corticotrope cells in
      vivo and in vitro. Two other proinflammatory transcription factors, namely signal
      transducer and activator of transcription (STAT)3 and NFkappaB, were
      significantly activated and partially colocalized with NF-IL6-IR in cells of the
      AL only after LPS-stimulation, but not following psychological stress. In vitro
      NF-IL6-activation was associated with induction and secretion of TNFalpha in
      folliculostellate cells, which could be antagonized by the JAK-STAT-inhibitor
      AG490. CONCLUSIONS: We revealed, for the first time, that NF-IL6 activation
      occurs not only during inflammatory LPS stimulation, but also during
      psychological stress, that is, a novel environment. Both stressors were
      associated with time-dependent activation of NF-IL6 in different cell types of
      the brain and the pituitary. Moreover, while NF-IL6-IR was partially linked to
      STAT3 and NFkappaB activation, TNFalpha production, and ACTH-IR after LPS
      stimulation; this was not the case after exposure to a novel environment,
      suggesting distinct underlying signaling pathways. Overall, NF-IL6 can be used as
      a broad activation marker in the brain and might be of interest for therapeutic
      approaches not only during inflammatory but also psychological stress.

PMID- 24279608
TI  - Pyoderma gangrenosum in refractory celiac disease: a case report.
AB  - BACKGROUND: Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis
      characterized by painful cutaneous ulcerations and often associated with systemic
      inflammatory and neoplastic diseases. Here we report the first case of pyoderma
      gangrenosum in a patient with refractory celiac disease. CASE PRESENTATION: A 52
      year-old woman with a previously diagnosed refractory celiac disease resistant to
      steroids and immunosuppressive drugs presented to our hospital for a rapidly
      growing, painful inflammatory skin lesion of the left leg. Physical examination
      revealed a painful lesion with focal ulceration, necrosis and pus discharge with
      active inflammatory borders at the external part of the left leg. Histological
      evaluation of a skin biopsy and analysis of inflammatory cytokines and matrix
      degrading proteases in lesional skin samples confirmed the clinical suspicion of
      pyoderma gangrenosum. Treatment with oral prednisone was rapidly followed by a
      complete healing of the skin lesion but no improvement of symptoms/signs of
      malabsorption. CONCLUSION: Treatment of the patient with systemic steroids healed
      the skin lesion without improving the underlying refractory celiac disease. This
      observation raises the possibility that refractory celiac disease and pyoderma
      gangrenosum may be immunologically different.

PMID- 24279609
TI  - The protective effect of L-carnitine against hippocampal damage due to
      experimental formaldehyde intoxication in rats.
AB  - We investigated the protective effects of L-carnitine on hippocampus tissue
      damage in rats during experimental formaldehyde (FA) intoxication. Male Wistar
      albino rats were assigned into four groups: (1) control (C), (2) formaldehyde
      (FA), (3) formaldehyde + 0.5 g/kg of L-carnitine (FA + 0.5 LC) (4) formaldehyde +
      1 g/kg L-carnitine (FA + 1 LC). At the end of the 14 day trial period, animals
      were sacrificed by decapitation under anesthesia. The hippocampus tissue samples
      were extracted to measure MDA, GSH and SOD activity. Neuronal degeneration was
      assessed based on histopathological (hematoxylin and eosin) and
      immunohistochemical (anti-ubiquitin) examination. To detect oxidative stress,
      specimens were reacted with anti-Cu/Zn-SOD antibody. After administering L
      carnitine with FA to the animals, the activities of SOD and GSH increased, but
      the levels of MDA decreased in hippocampus tissue. Neuronal degeneration was
      observed in the FA group. L-carnitine administration reduced neuronal
      degeneration and histological structure was similar to controls. After FA
      application, degenerated hippocampus neurons were stained with anti-ubiquitin and
      Cu/Zn-SOD antibodies; weakly positive staining was observed in L- carnitine
      treated groups. L-carnitine may be useful for preventing oxidative damage in the
      hippocampus tissue due to formaldehyde intoxication.

PMID- 24279610
TI  - Telomerase activity-independent function of telomerase reverse transcriptase is
      involved in acrylamide-induced neuron damage.
AB  - Polyacrylamide is used widely in industry, and its decomposition product,
      acrylamide (ACR), readily finds its way into commonly consumed cosmetics and
      baked and fried foods. ACR exerts potent neurotoxic effects in human and animal
      models. Telomerase reverse transcriptase (TERT), the catalytic subunit of
      telomerase, traditionally has been considered to play an important role in
      maintaining telomere length. Emerging evidence has shown, however, that TERT
      plays an important role in neuroprotection by inhibiting apoptosis and
      excitotoxicity, and by promoting angiogenesis, neuronal survival and
      neurogenesis, which are closely related to the telomere-independent functions of
      TERT. We investigated whether and how the TERT pathway is involved in ACR induced
      neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced
      the viability of cortical neurons as measured by MTT assay, 2) induced neuron
      apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow
      cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4)
      decreased bcl-2 expression of cortical neurons. ACR also increased intracellular
      ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH
      Px levels in mitochondria in a dose-dependent manner. We found that TERT
      expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0
      mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however,
      was undetectable in rat cortical neurons. Our results suggest that the TERT
      pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may
      exert its neuroprotective role in a telomerase activity-independent way,
      especially in mitochondria.

PMID- 24279611
TI  - HbA1c tracking and bio-psychosocial determinants of glycaemic control in children
      and adolescents with type 1 diabetes: retrospective cohort study and multilevel
      analysis.
AB  - OBJECTIVES: To explore the association between HbA1c 6 months after diagnosis (6
      m-HbA1c) and long-term glycaemic control in children with type 1 diabetes,
      accounting for other bio-psychosocial determinants. METHODS: This retrospective
      cohort study, included 155 children (<=16 yr) from the North of Scotland,
      diagnosed between January 1993 and August 2011, and receiving care between
      November 2008 and August 2012. Multilevel analysis explored the relationships
      between 6 m-HbA1c, other persistent or dynamic variables, and HbA1c. Patterns of
      glycaemic control were identified by cluster-analysis. RESULTS: 6 m-HbA1c was
      positively associated with diabetic ketoacidosis at diagnosis, shorter duration
      of partial-remission, female gender, and psychosocial adversity. In multilevel
      analysis the effects of 6 m-HbA1c on subsequent HbA1c trajectories remained
      significant after adjusting for patient- and observation-level predictors. An
      increase in 6 m-HbA1c of 10 mmol/mol (0.9%) was associated with an average
      increase in HbA1c levels of 5.3 (95% CI: 4.5-6.2) mmol/mol, or 0.48% (0.41 to
      0.57%; p < 0.001) over the follow-up period. Coefficients for linear and
      quadratic growth identified sustained effects of 6 m-HbA1c on glycaemic control
      (p < 0.001). Higher average levels or accelerated increases in HbA1c were
      associated with age at diagnosis, falling BMI (in girls > boys), mental health
      diagnosis, major adverse life-events, single-parenting, child welfare concerns,
      neighbourhood deprivation, and clinic non-attendance. Cluster-analysis identified
      groups with poor or deteriorating control, characterized by older age at
      diagnosis, multiple psychosocial adversities, and maladaptive healthcare use.
      CONCLUSION: Early HbA1c predicted future glycaemic control across childhood.
      Trajectories were further modified by biological factors, exposures to
      psychosocial adversity, and healthcare use.

PMID- 24279612
TI  - Developing templates for uniform data documentation and reporting in critical
      care using a modified nominal group technique.
AB  - BACKGROUND: Clinical practice in trauma and critical care is predominantly
      derived from quantitative observational cohort studies based on data
      retrospectively collected from medical records. Such data create uncontrolled
      bias and influence external and internal validity, thereby hindering systematic
      reviews. Templates or standards for uniform documenting and scientific reporting
      may result in high quality and internationally standardised data being collected
      on a regular basis, enhance large international multi-centre studies, and
      increase the quality of evidence. Templates or standards may be developed using
      multidisciplinary expert panel consensus methods.We present three consensus
      processes aimed at developing templates for documenting and scientific reporting.
      We discuss the advantages, limitations, and possible future improvements of our
      method. METHODS: The template preparation was based on expert panel consensus
      derived through a modified nominal group technique (NGT) method that combined the
      traditional Delphi method with the traditional NGT method in a four-step process.
      RESULTS: Standard templates for documenting and scientific reporting were
      developed for major trauma, pre-hospital advanced airway handling, and physician
      staffed pre-hospital EMS. All templates were published in scientific journals.
      CONCLUSION: Our modified NGT consensus method can successfully be used to
      establish templates for reporting trauma and critical care data. When used in a
      structured manner, the method uses recognised experts to achieve consensus, but
      based on our experiences, we recommend the consensus process to be followed by
      feasibility, reliability, and validity testing.

PMID- 24279613
TI  - The effects of Eculizumab on the pathology of malignant atrophic papulosis.
AB  - BACKGROUND: Degos disease is a frequently fatal and incurable occlusive
      vasculopathy most commonly affecting the skin, gastrointestinal tract and brain.
      Vascular C5b-9 deposition and a type I interferon (IFN) rich microenvironment are
      held to be pathogenetically important in the evolution of the vascular changes.
      We recently discovered the use of eculizumab as a salvage drug in the treatment
      of near fatal Malignant atrophic papulosis (MAP). The effects of eculizumab on
      the pathology of MAP are explored. METHODS: Archival skin and gastrointestinal
      biopsy material was procured over a 2.5-year period before and after eculizumab
      therapy in our index case. Routine light microscopy and immunohistochemical
      assessment for C3d, C4d, C5b-9, MxA and caspase 3 were examined. Direct
      immunofluorescent studies were also conducted on select biopsy material. RESULTS:
      The patient had received eculizumab as a emergent life saving measure and
      following rapid improvement he continued with biweekly infusions for 4 years.
      Although improved he continues to have signs and symptoms of persistent abdominal
      disease. Pre-Eculizumab biopsies showed an active thrombotic microangiopathy
      associated with a high type I interferon signature and extensive vascular
      deposits of C5b-9 in skin and gastrointestinal biopsies. Endothelial cell
      apoptosis as revealed by Caspase 3 expression was noted. Inflammation comprising
      lymphocytes and macrophages along with mesenchymal mucin was observed as well.
      Post-eculizumab biopsies did not show active luminal thrombosis but only chronic
      sequelae of prior episodes of vascular injury. There was no discernible caspase 3
      expression. After 12 months of therapy, C5b-9 was no longer detectable in tissue.
      The high type I IFN signature and inflammation along with mucin deposition was
      not altered by the drug. In addition, there was little effect of the drug on the
      occlusive fibrointimal arteriopathy which appears to be one characterized by
      extensive myofibroblastic expansion of the intima potentially as revealed by
      staining for smooth muscle actin without immunoreactivity for desmin and
      myogenin. CONCLUSIONS: Complement activation and enhanced endothelial cell
      apoptosis play an important role in the thrombotic complications of MAP. However,
      the larger vessel proliferative intimal changes appear to be independent of
      complement activation and may be on the basis of other upstream mechanisms.
      Monitoring C5b-9 deposition in tissue is likely not of great value in assessing
      treatment response to eculizumab given the persistence of C5b-9 in tissue for
      several months despite clinically effective C5 blocking therapy. A more
      integrated approach addressing upstream and downstream pathways in addition to
      those attributable to complement activation are critical for the successful
      treatment of MAP. Eculizumab may be used as salvage therapy in critically ill
      patients with thrombotic microangiopathy.

PMID- 24279614
TI  - HIV-1 genetic diversity in Russia: CRF63_02A1, a new HIV type 1 genetic variant
      spreading in Siberia.
AB  - One of the factors determining a high degree of heterogeneity in the HIV
      population is recombination-based variation, which leads to the emergence of the
      virus variants with a mosaic genome. An example is CRF63_02A1, an HIV-1 variant
      currently spreading in the Siberian region of Russia. To prove that this HIV-1
      variant is a new circulating recombinant form that had emerged as a result of
      repeated recombination between CRF02_AG and subtype A, we have isolated seven
      full-length HIV genomes and theoretically analyzed them, that is, reconstructed
      the phylogenetic relationships, determined recombination breakpoints and regions,
      and compared them with the regions known for CRF02_AG.

PMID- 24279615
TI  - Negotiating respectability: migrant women workers' perceptions of relationships
      and sexuality in free trade zones in Sri Lanka.
AB  - Migration has implications for women's sexual and reproductive health and rights.
      Our purpose with this study was to explore unmarried migrant women's perceptions
      of relationships and sexuality in the context of Sri Lankan Free Trade Zones.
      Sixteen semi-structured qualitative interviews were analyzed using thematic
      analysis. We found that the women's perceptions were influenced by gendered
      hegemonic notions of respectability and virginity. Complex gender relations both
      worked in favor of and against women's sexual and reproductive health and rights.
      Programs for improvement of migrant women's health should be informed by
      contextualized analysis of gender relations with its various dimensions and
      levels.

PMID- 24279616
TI  - Estimation of chloroform inhalation dose by other routes based on the
      relationship of area under the blood concentration-time curve (AUC)-inhalation
      dose to chloroform distribution in the blood of rats.
AB  - The present study investigated the time-course changes of concentration of
      chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3
      by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups
      caused a commensurate increase in the concentration of CHCl3 in the blood and the
      area under the blood concentration-time curve (AUC). There was good correlation
      (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the
      AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral
      administration, inhalation equivalent doses of orally administered CHCl3 were
      calculated. Calculation of inhalation equivalent doses allows the body burden due
      to CHCl3 by inhalation exposure and oral exposure to be directly compared. This
      type of comparison facilitates risk assessment in humans exposed to CHCl3 by
      different routes. Our results indicate that when calculating inhalation
      equivalent doses of CHCl3, it is critical to include the AUC from the exposure
      period in addition to the AUC after the end of the exposure period. Thus, studies
      which measure the concentration of volatile organic compounds in the blood during
      the inhalation exposure period are crucial. The data reported here makes an
      important contribution to the physiologically based pharmacokinetic (PBPK)
      database of CHCl3 in rodents. 

PMID- 24279617
TI  - Association of cigarette smoking with reproductive hormone levels and semen
      quality in healthy adult men in Taiwan.
AB  - The objective of this study was to evaluate the association of cigarette smoking
      with semen quality and reproductive hormone levels in 192 healthy men 20-65 years
      old, Kaohsiung, Taiwan. Exposure to cigarette smoking was classified three ways
      based on: 1) smoking status (yes vs. no); 2) the number of cigarettes per day (0,
      1-10, > 10); and 3) pack-years (0, 1-10, 11-20, > 20). Serum levels of total
      testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      and total estradiol (TE) were measured. Semen quality, including concentration,
      motility, vitality, and morphology, were assessed. Mean levels of smoking, semen
      quality, and hormones were compared using the multiple linear regression, while
      controlling for possible confounding factors, including age, body mass index
      (BMI), cadmium levels in seminal plasma, and alcohol consumption. Current
      smokers, who smoked 10 cigarettes per day, had a lower mean percentage of normal
      morphology (3.2% and 5.5% in nonsmokers, P = 0.040), and a higher mean level of
      TT (454.7 pmol/L and 439.8 pmol/L in nonsmokers, P = 0.048), as compared with
      nonsmokers. Also, current smokers at > 20 pack-year had a lower percentage of
      normal morphology and a lower mean level of TT as compared with nonsmokers; no
      significant difference was observed in LH, FSH, sperm concentration, vitality,
      and motility between smokers and nonsmokers based on the number of cigarette per
      day and the pack-year. Sperm vitality statistically correlated with FSH (beta = 
      0.36 P = 0.015) and TE (beta = 0.35, P = 0.018), while motility statistically
      correlated with TT (beta = 0.228, P = 0.045). Normal morphology did not
      statistically correlated with all reproductive hormones. 

PMID- 24279618
TI  - Comparative study of hematological responses to platinum group metals, antimony
      and silver nanoparticles in animal models.
AB  - Research was conducted to examine the hematological effects of heavy metals
      (platinum (Pt ((IV))), palladium (Pd ((II))), rhodium (Rh ((III))), antimony (Sb
      ((III)) and Sb ((V))), and silver nanoparticles (AgNPs)) on white blood cells in
      mammalian (rat) and avian (chick embryo) models. These metals are used in many
      everyday products and are accumulating in our environment. Six-week old Sprague
      Dawley female rats were treated daily by gavage and six-day old, fertile,
      specific pathogen-free white leghorn strain chick embryos' eggs were injected on
      days 7 and 14 of incubation with 0.0, 1.0, 5.0 or 10.0 ppm concentrations of Pt
      ((IV)) and a platinum group metal (PGM) mix of Pt ((IV)), Pd ((II)) and Rh
      ((III)). Chick embryos were also tested with 1.0 or 5.0 ppm of antimony compounds
      (Sb ((III)) and Sb ((V))) and 0.0, 15.0, 30.0, 60.0, or 100.0 ppm of silver
      nanoparticles (AgNPs). After 8 weeks of treatment, blood was obtained from the
      rats by jugular cut down and from chick embryos on day 20 of incubation by heart
      puncture. Blood smears were made and stained and a differential white cell count
      was performed on each. Examination of the smears revealed unconventional dose
      responses, stimulation of the immune response, and decreases in leukocyte
      production with various metals and concentrations. Chick embryos responded
      differently than rats to Pt and the PGM mix; suggesting that species differences
      and/or stage of development are important components of response to heavy metals.
      Route of administration of the metals might also influence the response. All of
      the heavy metals tested affected the immune responses of the tested animals as
      demonstrated by changes in the types and numbers of leukocytes. Our findings
      warrant further research to determine the mechanism of these effects and to
      understand and prevent toxicological effects in humans and other living
      organisms. 

PMID- 24279619
TI  - Personal exposure levels of PAHs in the general population in northern rural area
      of Jiangsu Province, China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds that are
      produced by incomplete combustion of organic matters. Studies in humans have
      shown associations between PAHs exposure and development of cancers. Urinary
      monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH
      metabolites used as biomarkers for estimating human exposure to PAHs. We
      collected 332 urinary samples from a nonoccupational population in northern rural
      area of Jiangsu. Levels of 2-hydroxynathalene (2-OHN), 2-hydroxyfluorene (2-OHF)
      and 1-hydroxypyrene (1-OHP) were measured as biomarkers to assess body PAHs
      burdens. Three PAH metabolites were detected in more than 80% of urinary samples.
      After being adjusted with urinary creatinine concentration, the urinary
      concentrations were determined as 2-OHF > 1-OHP > 2-OHN in terms. The medians of
      2-OHN, 2-OHF, 1-OHP for the general population were 1.74, 30.01, 25.24 MUmoL/moL
      creatinine, respectively. The results demonstrated that nonoccupational
      populations in northern rural area of Jiangsu were exposed to extremely high
      PAHs. The urinary concentration (median and geometric mean) of 2-OHN,2-OHF,1-OHP
      in males (1.90, 0.37 +/- 0.46; 34.90, 1.53 +/- 0.41; 27.84, 1.52 +/- 0.29
      MUmoL/moL creatinine, respectively) was slightly higher than in females (1.56,
      0.32 +/- 0.42; 29.60, 1.48 +/- 0.40; 23.13, 1.49 +/- 0.32 MUmoL/moL creatinine,
      respectively). However, only 2-OHN was different significantly between males and
      females. 

PMID- 24279620
TI  - Effects of ionization on the toxicity of silver nanoparticles to Japanese medaka
      (Oryzias latipes) embryos.
AB  - Increase in the use of manufactured nanomaterials (NMs) has led to concerns about
      the environmental impacts. Especially, hazard of metal-based NMs is more severe
      due to ions released from surface by water quality parameters and physicochemical
      properties after entering into the water environment. However, little is known
      about the effects of ionization on the toxicity of metal-based NMs in the water
      environment. To address this question, we prepared the suspensions of silver
      nanoparticles (AgNP) at 25 MUg L(-1) containing different concentrations of Ag(+)
      (5, 10, 20, 45, and 75% Ag(+) to total Ag), and evaluated their toxicity to
      Japanese medaka (Oryzias latipes) embryos. Higher Ag(+) ratios in the AgNP
      suspension, suggesting the lower number of particles, led to the higher adverse
      effects on embryos and sac-fries. In addition, histopathology analysis revealed
      that AgNPs penetrated through chorion of eggs and skin membrane, and were
      distributed into the tissues. The results imply that the ionization could
      decrease the toxicity of metal-based NMs in the water environment. 

PMID- 24279621
TI  - Naphthenic acids quantification in organic solvents using fluorescence
      spectroscopy.
AB  - Quantification of naphthenic acids in water has been traditionally performed
      after extraction with organic solvents followed by analytic methods that are
      complex and costly for preliminary research or for continuous monitoring
      purposes. This study examines the application of fluorescence in organic solvents
      as an effective alternative, and the role of organic solvents on quantification
      results. Nine organic solvents were used: three polar protic alcohols (methanol,
      ethanol, and propanol), three polar aprotic (dichloromethane, acetone, and
      acetonitrile) and three non-polar (hexane, toluene, and diethyl ether). The
      calibration curves of the polar protic solvents performed the best; they had
      lower light scattering and higher method sensitivity than polar aprotic and non
      polar. Methanol was selected for further experiments having a strong linearity
      for concentrations lower than 250 mg/L (R(2) > 0.99), and a low relative standard
      deviation (< 10%). The method sensitivity was improved by 70% using a methanol
      deionized water mixture (50:50) as a solvent. The synchronous fluorescence mode
      with a reduced offset value of Deltalambda = 10 nm demonstrated potential for
      fingerprinting. The fluorescence technique for quantifying total naphthenic acids
      directly in organic solvents is a cost-effective analytical method compatible
      with the solid phase extraction of the sample. 

PMID- 24279622
TI  - Enhanced removal of aqueous BPA model compounds using Metalloligs.
AB  - A model compound, 4-(t-butyl)phenol, was used as a substitute for BPA (bisphenol
      acetone or Bisphenol A) a material used for the production of a large volume of
      common plastics. Unfortunately, BPA is suspected to have estrogenic properties,
      and there is a suspicion that even small amounts can have a deleterious effect
      against humans, especially female infants. The model compound has some
      similarities to BPA, but lacks some of the serious properties of BPA dust. Since
      other workers have demonstrated the capability of removing BPA from plastics by
      extraction with saline or alcohol, we studied whether Octolig, a
      polyethylenediimine supported on silica gel, or transition metal derivatives of
      Octolig could be used to remove concentrations for model compounds from aqueous
      solution. Octolig gave modest results 20%, the manganese (II) and iron (III)
      derivatives gave poor results, Cuprilig was an improvement over those two
      Metalloligs, but the cobalt(II) derivative was able to remove up to 56% of the
      model compound. Two methods were studied, batch and column chromatography. Under
      the conditions used in this study, the batch method was superior. 

PMID- 24279623
TI  - Temporal trends analysis of 2004 to 2012 toxicity and pesticide data for
      California's Central Valley water quality coalitions.
AB  - This study was designed to assess temporal trends of 2004-2012 toxicity data from
      three water column tests, one sediment test and concentrations of three
      pesticides from four Central Valley Water Quality Coalitions in California. Major
      conclusions based on this extensive toxicity and pesticide data from 150 mainstem
      and tributary sites showed a significant decline in toxicity over 9 years from
      Ceriodaphnia dubia water column toxicity tests and a significant decline in
      toxicity from three water column and one sediment toxicity test combined. The
      organophosphate insecticides diazinon and chlorpyrifos also showed a significant
      decline in concentrations from 2004 to 2012 and also a significant decline in the
      percent of samples that exceeded water quality objectives for both of these
      insecticides. The analysis conducted did not show any cases of either increased
      toxicity or pesticide concentrations over the 9-year period. The final conclusion
      from this analysis is that water quality conditions in the Central Valley Region
      of California, as measured by the toxicity and pesticide data from this study,
      have improved from 2004 to 2012. 

PMID- 24279624
TI  - Oxidation products and degradation pathways of 4-chlorophenol by catalytic
      ozonation with MnOx/gamma-Al2O3/TiO2 as catalyst in aqueous solution.
AB  - To identify the intermediates of 4-chlorophenol (4-CP) and bring forward the
      degradation pathways in the process of catalytic ozonation of 4-CP, 4-CP was
      ozonated with MnOx/gamma-Al2O3/TiO2 (MAT) catalyst, and 4-CP was almost
      decomposed within 30 min, the mineralization reaching above 94.1% at 100 min. The
      evident reduction of the degradation with the addition of the radical scavenger
      tert-butanol (TBA) and the stronger spin-adduct signals of 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) indicated that 4-CP was oxidized primarily by hydroxyl
      radical (.OH). Analysis of GC-MS, HPLC and IC confirmed that aromatic compounds
      and carboxylic acids were predominant oxidative organic intermediates of 4-CP in
      catalytic ozonation.The main degradation steps were hydroxylation of 4-CP and the
      formation of hydroquinone, 4-chlororesorcinol and 4-chlorocatechol. The low
      molecular weight (LMW) acids, such as malic, malonic, oxalic, acetic, and formic
      acid, were formed from the further oxidation of the intermediates. 

PMID- 24279625
TI  - Analytical and experimental analysis of solute transport in heterogeneous porous
      media.
AB  - Knowledge of solute transport in heterogeneous porous media is crucial to monitor
      contaminant fate and transport in soil and groundwater systems. In this study, we
      present new findings from experimental and mathematical analysis to improve
      current understanding of solute transport in structured heterogeneous porous
      media. Three saturated columns packed with different sand combinations were used
      to examine the breakthrough behavior of bromide, a conservative tracer.
      Experimental results showed that bromide had different breakthrough responses in
      the three types of sand combinations, indicating that heterogeneity in hydraulic
      conductivity has a significant effect on the solute transport in structured
      heterogeneous porous media. Simulations from analytical solutions of a two-domain
      solute transport model matched experimental breakthrough data well for all the
      experimental conditions tested. Experimental and model results show that under
      saturated flow conditions, advection dominates solute transport in both fast-flow
      and slow-flow domains. The sand with larger hydraulic conductivity provided a
      preferential flow path for solute transport (fast-flow domain) that dominates the
      mass transfer in the heterogeneous porous media. Importantly, the transport in
      the slow-flow domain and mass exchange between the domains also contribute to the
      flow and solute transport processes and thus must be considered when
      investigating contaminant transport in heterogeneous porous media. 

PMID- 24279626
TI  - Alternative chelating agents: evaluation of the ready biodegradability and
      complexation properties.
AB  - The ready biodegradability of four chelating agents, N,N'-(S,S)-bis[1-carboxy-2
      (imidazol-4-yl)ethyl]ethylenediamine (BCIEE), N'-ethylenedi-L-cysteine (EC), N,N'
      bis (4-imidazolymethyl)ethylenediamine (EMI) and 2,6-pyridine dicarboxylic acid
      (PDA), was tested according to the OECD guideline for testing of chemicals. PDA
      proved to be a readily biodegradable substance. However, none of the other three
      compounds were degraded during the 28 days of the test. Chemical simulations were
      performed for the four compounds in order to understand their ability to complex
      with some metal ions (Ca, Cd, Co, Cu, Fe, Mg, Mn, Ni, Pb, Zn) and discuss
      possible applications of these chelating agents. Two different conditions were
      simulated: (i) in the presence of the chelating agent and one metal ion, and (ii)
      in the simultaneous presence of the chelating agent and all metal ions with an
      excess of Ca. For those compounds that were revealed not to be readily
      biodegradable (BCIEE, EC and EMI), applications were evaluated where this
      property was not fundamental or even not required. Chemical simulations pointed
      out that possible applications for these chelating agents are: food
      fortification, food process, fertilizers, biocides, soil remediation and
      treatment of metal poisoning. Additionally, chemical simulations also predicted
      that PDA is an efficient chelating agent for Ca incrustations removal, detergents
      and for pulp metal ions removal process. 

PMID- 24279627
TI  - Full-scale biological treatment of tannery wastewater using the novel microbial
      consortium BM-S-1.
AB  - In order to develop a more effective and eco-friendly treatment technology, a
      full-scale tannery wastewater treatment plant with a sludge digestion system was
      augmented with a novel microbial consortium (BM-S-1). The aim of this study was
      to determine if the BM-S-1 could successfully treat the tannery wastewater in a
      full-scale treatment system without chemical pretreatment and to investigate
      effect of the augmentation on sludge production. Chemical oxygen demand (COD),
      total nitrogen (TN), total phosphorus (TP), chromium (Cr) and mixed liquor
      suspended solids (MLSS) were measured to monitor treated water quality and
      treatment efficiency. Microbial community structures in the treatment were also
      examined using pyrosequencing analysis of 16S rRNA gene and quantitative PCR
      (qPCR) of the nitrous oxide reductase gene (nosZ). The removal efficiencies of
      COD, TN, TP, and Cr were estimated to be 98.3%, 98.6%, 93.6%, and 88.5%,
      respectively, while the system without a continuous augmentation was broken down.
      The pyrosequencing analysis showed Brachymonas denitrificans to be the most
      dominant microbial population in the buffering tank (B; 37.5%). Potential
      polymeric substance degraders (Clostridia), sulfate reducers (Desulfuromonas
      palmitatis), and sulfur oxidizers (uncultured Thiobacillus) were dominant in the
      sludge digestion (SD) tank. The denitrifiers assayed by nosZ qPCR were dominant
      in B and SD. These microbial communities appeared to play important roles in
      removing nutrients and odor, and reducing sludge in the wastewater treatment
      plant without chemical pretreatment. 

PMID- 24279628
TI  - Response to "Refutation of dirty electricity hypothesis in obesity:
      epistemological arguments and trans-disciplinary study using an instrumental
      variable" by Frank de Vocht and Igor Burstyn.

PMID- 24279629
TI  - Refutation of dirty electricity hypothesis in obesity: epistemological arguments
      and trans-disciplinary study using an instrumental variable.

PMID- 24279630
TI  - No genotoxic effect in exfoliated bladder cells of rat under the exposure of 1800
      and 2100 MHz radio frequency radiation.
AB  - In this study, we aimed to investigate the effects of 1800 and 2100 MHz Radio
      Frequency (RF) radiation on the number of micronucleus (MN) in exfoliated bladder
      cells of rat which shows the genotoxic damage. Exposure period was 30 min/day, 6
      days/week for a month and two months exposure periods. Thirty male wistar albino
      rats were used for five groups: Group I (n = 6): 1800 MHz RF exposed animals for
      one month, Group II (n = 6): 2100 MHz RF exposed animals for one month, Group III
      (n = 6): 2100 MHz RF exposed for two months, Group IV (n = 6): control group for
      one month, Group V (n = 6): control group for two months. Rats of the control
      groups were housed in their home cages during the entire experimental period
      without subjecting to any experimental manipulation. 1800 and 2100 MHz RF
      exposures did not result in any significant MN frequencies in rat bladder cells
      with respect to the control groups (p > 0.05). There was no statistically
      significant difference between 2100 MHz RF exposed groups, either. Further
      studies are needed to demonstrate if there is any genotoxic effect, micronucleus
      formation in other tissues of rats.

PMID- 24279632
TI  - The effects of different intensities, frequencies and exposure times of extremely
      low-frequency electromagnetic fields on the growth of Staphylococcus aureus and
      Escherichia coli O157:H7.
AB  - The impact of different types of extremely low-frequency electromagnetic fields
      (ELF-EMF) on the growth of Staphylococcus aureus and Escherichia coli O157:H7 was
      investigated. The cultures of bacteria in broth media were exposed to sinusoidal
      homogenous ELF-EMF with 2 and 4 mT magnetic intensities. Each intensity for each
      bacteria was combined with three different frequencies (20, 40 and 50 Hz), and
      four different exposure times (1, 2, 4 and 6 h). A cell suspension of each
      experiment was diluted for the appropriate range and inoculated to Mueller-Hinton
      Agar (MHA) plates after exposure to ELF-EMF. The number of colony forming units
      (CFU) of both strains was obtained after incubation at 37  degrees C for 24 h.
      Data were statistically evaluated by one-way analysis of variance (ANOVA),
      statistical significance was described at p < 0.05 and data were compared with
      their non-exposed controls. Magnetic intensity, frequency and exposure time of
      ELF-EMFs changed the characteristic responses for both microorganisms. Samples
      exposed to ELF-EMF showed a statistically significant decrease compared to their
      controls in colony forming capability, especially at long exposure times. An
      exposure to 4 mT-20 Hz ELF-EMF of 6 h produced maximum inhibition of CFU compared
      to their controls for both microorganisms (95.2% for S. aureus and 85% for E.
      coli).

PMID- 24279633
TI  - Glomerular filtration rates in healthy Asians without kidney disease.
AB  - AIM: The Chronic Kidney Disease Collaboration - Epidemiology (CKD-EPI) glomerular
      filtration rates (GFR) estimation equation is believed to estimate GFR more
      accurately in healthy people but this has not been validated in Asians. We
      studied the distribution of GFR in a multi-ethnic Asian population without CKD,
      and compared the performance of measures of GFR estimation, including the CKD-EPI
      equation, Cockroft-Gault equation, and 24-hour urine creatinine clearances.
      MATERIALS AND METHODS: A total of 103 healthy volunteers without a history of
      kidney disease, hypertension, or diabetes underwent GFR measurement using 3
      sample plasma clearance of (99m) Tc-DTPA. Cockroft-Gault estimated GFR and 24
      hour urine creatinine clearances were normalized to body surface area. RESULTS:
      The mean measured GFR was 101 +/- 15.8 mL/min per 1.73 m(2) and was lowest in
      Indians (93 +/- 12.3 mL/min per 1.73 m(2); P < 0.001). The CKD-EPI equation
      appears to be more accurate for healthy participants. Estimated GFR correlated
      with measured GFR (r = 0.57, P < 0.001), and the mean difference is 3.72 +/-
      14.43 mL/min per 1.73 m(2) (P < 0.001). However, estimating GFR using self
      directed 24-hour urine creatinine clearances is poorer than using the CKD-EPI
      equation. CONCLUSIONS: GFR estimation using self-directed 24-hour urine
      collection for creatinine clearance is less accurate than using the CKD-EPI
      equation. A larger study is required to clarify GFR in healthy Asians, and the
      association of health outcomes of Asian kidney donors with lower GFR thresholds.

PMID- 24279634
TI  - Infertility treatment for azoospermic patients with a history of infectious
      parotitis (mumps) using combined techniques.
AB  - PURPOSE: The purpose of this study was to investigate the clinical efficacy of in
      vitro maturation-intracytoplasmic sperm injection (IVM-ICSI) technique on the
      treatment of azoospermic patients with a history of infectious parotitis (mumps).
      METHODS: Spermatozoa were obtained from the testes of azoospermic patients with a
      history of mumps and fertilized by ICSI. Eggs were retrieved from the spouse of
      patients in the natural cycle. Fertilized embryos were transferred into the
      uterus of patients' respective spouses. RESULTS: Live sperm were retrieved from
      16 of out of 24 (67%) azoospermic patients with a history of mumps. Using IVM
      ICSI, the normal fertilization rate was 71.2%. A total of 23 treatment cycles
      were completed in the spouses of 16 patients and of these, 9 patients' spouses
      became pregnant (a pregnancy rate of 39.1%). The success rate for infertility
      treatment of mumps patients was equally high at 56.3% (9/16). CONCLUSION: The IVM
      ICSI technique is a simple, effective and economic method for infertility
      treatment in azoospermic patients with a history of mumps.

PMID- 24279636
TI  - A crusted lesion on the penis.

PMID- 24279635
TI  - Topical Brazilian propolis improves corneal wound healing and inflammation in
      rats following alkali burns.
AB  - BACKGROUND: The objective of this study was to investigate the effects of the
      Brazilian Scaptotrigona sp propolis, a widely used folk medicine, in corneal
      wound healing and inflammation. METHODS: Corneal epithelial defects of 1 mm in
      diameter were made in the right eyes of Wistar male adult rats by cauterization
      with silver nitrate sticks. Subsequently, they were divided in two groups (n = 40
      rats/group): Brazilian propolis (BP) group was topically treated with a
      microemulsion containing 1% Brazilian propolis; vehicle (VH) group received the
      same formulation without propolis. The epithelial defect area was photographed
      and measured at t = 0 (wound induction), and after 12, 24, 48 and 120 h of
      treatment. The inflammatory response was evaluated based on counting of
      neutrophils. Epithelial regeneration rates were determined based on Ki-67
      expression in basal epithelial cells. Comparisons were made using the Kruskal
      Wallis and the Mann-Whitney U test. RESULTS: The BP group presented both smaller
      epithelial defect areas at 12, 24 and 48 h and fewer corneal infiltrating
      neutrophils at 24 and 48 h (P < 0.01) than the VH group. These effects were
      associated with more pervasive Ki-67 staining in the BP group at 12 and 24 h (P <
      0.05). CONCLUSIONS: Topically applied BP accelerated wound healing and reduced
      the inflammatory response to silver nitrate-induced corneal alkali burns in rats.

PMID- 24279637
TI  - Comparative analysis of binding sites of human meprins with hydroxamic acid
      derivative by molecular dynamics simulation study.
AB  - Meprins are complex and highly glycosylated multi-domain enzymes that require
      post-translational modifications to reach full activity. Meprins are
      metalloproteases of the astacin family characterized by a conserved zinc-binding
      motif (HExxHxxGFxHExxRxDR). Human meprin-alpha and -beta protease subunits are
      55% identical at the amino acid level, however the substrate and peptide bond
      specificities vary markedly. Current work focuses on the critical amino acid
      residues in the non-primed subsites of human meprins-alpha and -beta involved in
      inhibitor/ligand binding. To compare the molecular events underlying ligand
      affinity, homology modeling of the protease domain of humep-alpha and -beta based
      on the astacin crystal structure followed by energy minimization and molecular
      dynamics simulation of fully solvated proteases with inhibitor Pro-Leu-Gly
      hydroxamate in S subsites were performed. The solvent accessible surface area
      curve shows a decrease in solvent accessibility values at specific residues upon
      inhibitor binding. The potential energy, total energy, H-bond interactions, root
      mean square deviation and root mean square fluctuation plot reflect the subtle
      differences in the S subsite of the enzymes which interact with different
      residues at P site of the inhibitor. 

PMID- 24279638
TI  - Interdisciplinary treatment of patients with fibromyalgia: improvement of their
      health-related quality of life.
AB  - OBJECTIVE: To assess whether an interdisciplinary intervention is more effective
      than usual care for improving the health-related quality of life (HRQoL) among
      patients with fibromyalgia (FM), and to identify variables that were predictors
      of improvement in HRQoL. METHODS: In a randomized controlled clinical trial
      carried out on an outpatient basis in a hospital pain management unit, 153
      patients with FM were randomly allocated to an experimental group (EG) or a
      control group (CG). Participants completed the Fibromyalgia Impact Questionnaire
      (FIQ) at baseline and 6 months after the intervention. The EG received an
      interdisciplinary treatment (12 sessions for 6 weeks) which consisted of
      coordinated psychological, medical, educational, and physiotherapeutic
      interventions while the CG received standard-of-care pharmacologic treatment.
      Descriptive statistics, ANOVA, Chi square and Fisher tests and generalized linear
      models were used for data analysis. RESULTS: Six months after the intervention,
      statistically significant improvements in HRQoL were observed in physical
      functioning (P = 0.01), pain (P = 0.03) and total FIQ score (P = 0.04) in the EG
      compared to the CG. The number of physical illnesses was identified as a
      predictor for improvement. CONCLUSIONS: This interdisciplinary intervention has
      shown effectiveness in improving the HRQoL of this sample of patients with FM.
      The number of physical illnesses was identified as a predictor of that
      improvement.

PMID- 24279639
TI  - Activation of muscarinic receptors protects against retinal neurons damage and
      optic nerve degeneration in vitro and in vivo models.
AB  - AIMS: Muscarinic acetylcholine receptor agonist pilocarpine reduces intraocular
      pressure (IOP) of glaucoma mainly by stimulating ciliary muscle contraction and
      then increasing aqueous outflow. It is of our great interest to know whether
      pilocarpine has the additional properties of retinal neuroprotection independent
      of IOP lowering in vitro and in vivo models. METHODS: In rat primary retinal
      cultures, cell viability was measured using an MTT assay and the trypan blue
      exclusion method, respectively. Retinal ganglion cells (RGCs) were identified by
      immunofluorescence and quantified by flow cytometry. For the in vivo study, the
      retinal damage after retinal ischemia/reperfusion injury in rats was evaluated by
      histopathological study using hematoxylin and eosin staining, transmission
      electron microscopy, and immunohistochemical study on cleaved caspase-3, caspase
      3, and ChAT. RESULTS: Pretreatment of pilocarpine attenuated glutamate-induced
      neurotoxicity of primary retinal neurons in a dose-dependent manner. Protection
      of pilocarpine in both retinal neurons and RGCs was largely abolished by the
      nonselective muscarinic receptor antagonist atropine and the M1-selective
      muscarinic receptor antagonist pirenzepine. After ischemia/reperfusion injury in
      retina, the inner retinal degeneration occurred including ganglion cell layer
      thinning and neuron lost, and the optic nerve underwent vacuolar changes. These
      degenerative changes were significantly lessened by topical application of 2%
      pilocarpine. In addition, the protective effect of pilocarpine on the ischemic
      rat retina was favorably reflected by downregulating the expression of activated
      apoptosis marker cleaved caspase-3 and caspase-3 and upregulating the expression
      of cholinergic cell marker ChAT. CONCLUSIONS: Taken together, this highlights
      pilocarpine through the activation of muscarinic receptors appear to afford
      significant protection against retinal neurons damage and optic nerve
      degeneration at clinically relevant concentrations. These data also further
      support muscarinic receptors as potential therapeutic neuroprotective targets in
      glaucoma.

PMID- 24279640
TI  - Monitoring acute phase proteins in retrovirus infected cats undergoing feline
      interferon-omega therapy.
AB  - OBJECTIVES: Recombinant feline interferon-omega therapy is an immunomodulator
      currently used in the treatment of different retroviral diseases including feline
      immune deficiency virus and feline leukaemia virus. Although its mechanism of
      action remains unclear, this drug appears to potentiate the innate response.
      Acute phase proteins are one of the key components of innate immunity and studies
      describing their use as a monitoring tool for the immune system in animals
      undergoing interferon-omega therapy are lacking. This study aimed to determine
      whether interferon-omega therapy influences acute phase protein concentrations
      namely serum amyloid-A, alpha-1-glycoprotein and C-reactive protein. METHODS: A
      single-arm study was performed using 16 cats, living in an animal shelter,
      naturally infected with retroviruses and subjected to the interferon-omega
      therapy licensed protocol. Samples were collected before (D0), during (D10 and
      D30) and after therapy (D65). Serum amyloid-A and C-reactive protein were
      measured by specific enzyme-linked immunosorbent assay kits and alpha-1
      glycoprotein by single radial immunodiffusion. RESULTS: All the acute phase
      proteins significantly increased in cats undergoing interferon-omega therapy
      (D0/D65: P<0.05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be
      reasonable predictors of innate-immune stimulation and may be useful in the
      individual monitoring of naturally retroviral infected cats undergoing interferon
      omega therapy.

PMID- 24279641
TI  - Direct determination of urinary creatinine by reactive-thermal desorption
      extractive electrospray-ion mobility-tandem mass spectrometry.
AB  - A direct, ambient ionization method has been developed for the determination of
      creatinine in urine that combines derivatization and thermal desorption with
      extractive electrospray ionization and ion mobility-mass spectrometry. The
      volatility of creatinine was enhanced by a rapid on-probe aqueous acylation
      reaction, using a custom-made thermal desorption probe, allowing thermal
      desorption and ionization of the monoacylated derivative. The monoacyl creatinine
      [M + H](+) ion (m/z 156) was subjected to mass-to-charge selection and collision
      induced dissociation to remove the acyl group, generating the protonated
      creatinine [M + H](+) product ion at m/z 114 before an ion mobility separation
      was applied to reduce chemical noise. Stable isotope dilution using creatinine-d3
      as internal standard was used for quantitative measurements. The direct on-probe
      derivatization allows high sample throughput with a typical cycle time of 1 min
      per sample. The method shows good linearity (R(2) = 0.986) and repeatability
      (%RSD 8-10%) in the range of 0.25-2.0 mg/mL. The creatinine concentrations in
      diluted urine samples from a healthy individual were determined to contain a mean
      concentration of 1.44 mg/mL creatinine with a precision (%RSD) of 9.9%. The
      reactive ambient ionization approach demonstrated here has potential for the
      determination of involatile analytes in urine and other biofluids. 

PMID- 24279642
TI  - Inflammatory activation and recovering BKV-specific immunity correlate with self
      limited BKV replication after renal transplantation.
AB  - As BKV-associated nephropathy has emerged as an important cause of allograft
      failure, it has been of major importance to find immune mechanisms suitable to
      identify kidney transplant recipients (KTRs) at increased risk of BKV
      replication. We monitored 29 KTRs with seven measurements during the first year
      post-transplantation. BKV-specific T cells directed to 5 BKV proteins were
      analyzed in an interferon-gamma ELISPOT assay. BKV-specific antibodies were
      measured using an ELISA. The extent of immunosuppression and inflammatory
      activation were quantified by measures of immune function including lymphocyte
      subpopulations, IP-10, and adhesion molecule serum levels. All 5 BKV-specific T
      cells increased significantly from diagnosis to resolution of BKV replication
      (P<0.001). While antistructural T cells were significantly higher in KTRs with
      BKV replication (P<0.05), no differences were observed for antismall t- and large
      T-antigen-directed T cells (P>0.05). Interestingly, 65% of KTRs without BKV
      replication showed transient appearance of antismall t- and large T-antigen
      directed T cells. Although no significant differences were observed for T-cell
      subpopulations and adhesion molecules, IP-10 levels increased significantly
      during BKV replication (P<0.05). Assessment of BKV-specific T cells identifies
      recovering BKV-specific immunity in KTRs with BKV replication and suggests their
      protective ability in KTRs without BKV replication. Increases in IP-10 levels
      stress the importance of infiltrating inflammatory leukocytes in the regulation
      of BKV replication and point to inflammatory activation in the pathogenesis of
      BKV replication.

PMID- 24279643
TI  - Baroreflex sensitivity, vascular risk factors, and cognitive function in a
      healthy elderly population: the PROOF cohort.
AB  - OBJECTIVES: To assess the role of the cardiac autonomic nervous system (ANS), as
      measured according to spontaneous cardiac baroreflex sensitivity (BRS), in the
      type and degree of cognitive performance in healthy young-elderly individuals,
      taking into account the presence of other vascular risk factors. DESIGN:
      Community-based cross-sectional study. SETTING: In-home and clinical settings.
      PARTICIPANTS: A subset of participants, aged 66.9+/-0.9, from a prospective study
      that aimed to assess the influence of ANS activity on cardiovascular and
      cerebrovascular morbidity and mortality (N=916). MEASUREMENTS: All subjects
      underwent a clinical interview, neuropsychological testing, and autonomic and
      vascular measurements. Three cognitive domains were defined: attentional (Trail
      Making Test Part A, Stroop code and parts I & II), executive (Trail-Making Test
      Part B, Stroop part III, verbal fluency and similarity tests), and memory (Benton
      visual retention test, Grober and Buschke procedure). Subjects were stratified
      according to their scores into normal, low, and impaired performers. RESULTS:
      After adjustments to demographic and vascular data, participants with moderate
      autonomic dysregulation (3<BRS<=6) were determined to be 1.82 times as likely to
      have memory impairment (odds ratio (OR)=1.82, 95% confidence interval (CI)=1.13
      3.17, P=.02) and those with severe autonomic dysregulation (BRS<=3) to be 2.65 as
      likely (OR=2.65, 95% CI=1.40-5.59, P=.006) as participants with normal BRS (>6).
      CONCLUSION: In older individuals without dementia, autonomic dysregulation seems
      to have a direct, gradual, and independent effect on memory. Future studies are
      needed to evaluate the long-term effects of BRS and other markers of the ANS on
      cognitive decline.

PMID- 24279644
TI  - Chemopreventive effects of berberine on intestinal tumor development in Apcmin/+
      mice.
AB  - BACKGROUND: Berberine, an isoquinoline alkaloid, has shown inhibitory effects on
      growth of several tumor cell lines in vitro. The aim of this study was to
      investigate chemopreventive effects of berberine on intestinal tumor development
      in Apcmin/+ mice. METHODS: Four-week old Apcmin/+ mice were treated with 0.05% or
      0.1% berberine in drinking water for twelve weeks. The number and the size of
      tumors were measured to evaluate intestinal tumor development. Tissue sections
      were prepared for PCNA and Ki-67 immunostaining to detect cell proliferation, and
      TUNEL assay and cleaved caspase-3 immunostaining for apoptosis. Western blot
      analysis and immunostaining were performed to detect the activation of Wnt and
      epidermal growth factor receptor (EGFR) signaling pathways and COX-2 expression
      in the intestinal tumor cells. The prostaglandin E2 level in the small intestine
      was detected using ELISA. RESULTS: Compared with untreated Apcmin/+ mice, the
      total numbers of tumors in the small intestine and the colon were reduced by
      39.6% and 62.5% in 0.05% and 0.1% berberine-treated mice, respectively. The
      numbers of tumors in proximal, middle, and distal segments of the small intestine
      in 0.1% berberine-treated mice were significantly reduced by 53.7%, 55.3%, and
      76.5% respectively. Berberine treatment also decreased the numbers of all sizes
      of tumors (>2 mm, 1-2 mm, and <1 mm) in the small intestine. Berberine suppressed
      tumor cell proliferation and increased apoptosis. Furthermore, berberine
      decreased the activation levels of Wnt and EGFR signaling pathways, and down
      regulated COX-2 expression in intestinal tumor cells and prostaglandin E2
      production in the small intestine. CONCLUSIONS: Berberine inhibits intestinal
      tumor development, which is correlated with its activity to suppress tumor cell
      proliferation and increase apoptosis in Apcmin/+ mice. Down-regulation of Wnt and
      EGFR signaling pathways and COX-2 expression by berberine may be involved in its
      anti-tumorigenic effects.

PMID- 24279646
TI  - Free analyte QC concept: a novel approach to prove correct quantification of free
      therapeutic protein drug/biomarker concentrations.
AB  - Quantification of free drug concentrations is highly challenging due to the
      dynamic drug-ligand equilibrium, which may result in incorrect results. Current
      QC concepts do not adequately cover all of the important influencing factors: the
      assay itself (format and procedure); the calibration concept; the sample
      preparation; and the sample storage. Here, we propose a 'free analyte QC concept'
      that enables quantitative testing of these four factors and, thus, provides best
      possible proof of correct free drug quantification. The principle of the free
      analyte QC concept and an example of its application for a free drug assay is
      described. A comparison of this novel approach with current approaches and how
      the new concept fits (or does not fit) with current regulatory guidelines is
      discussed.

PMID- 24279645
TI  - The effect of a novel curcumin derivative on pancreatic islet regeneration in
      experimental type-1 diabetes in rats (long term study).
AB  - BACKGROUND: Several studies highlight curcumin's benefit as a hypoglycemic agent,
      however; a limited number of reports present the importance of curcumin in
      improvement of pancreatic islets in diabetes. The aim of the present study is to
      evaluate the antidiabetic effect of a novel curcumin derivative and its effect on
      pancreatic islet regeneration in type I diabetes-induced by STZ. MATERIALS AND
      METHODS: Rats were divided into diabetic rats and diabetic rats treated orally
      with the novel curcumin derivative (NCD) for 40 days. Fasting blood samples were
      withdrawn periodically from all rats to estimate plasma glucose, insulin and C
      peptide for 10 months. Histopathology was performed to allow the assessment of
      pancreatic islet morphology. Insulin and CD105 were detected
      immunohistochemically. RESULTS: In diabetic rats, the plasma glucose, insulin and
      C-peptide levels remained within the diabetic range for about 4 months, after
      which a gradual decrease in glucose and increase in insulin and C-peptide was
      observed, which reached almost normal levels after 10 months. NCD treated
      diabetic rats showed significantly lowered plasma glucose and increased plasma
      insulin and C-peptide levels. This was followed by a further significant decrease
      in plasma glucose and increase in plasma insulin and C-peptide after two months
      from oral administration of the NCD. The plasma insulin and C-peptide continued
      to increase for ten months reaching levels significantly higher than the basal
      level. Histopathological examination of diabetic rat pancreas revealed absence of
      islets of Langerhans, minimal adipose tissue infiltration and localized
      lymphocytic infiltrates. However, after 6 months of induction of diabetes, rat
      pancreas showed the appearance of small well formed islets and positive insulin
      cells but no CD105 positive cells. NCD treated rats showed the appearance of
      primitive cell collections, large insulin positive cells and CD105 positive cells
      in the adipose tissue infiltrating the pancreatic tissues. This was followed by
      the gradual appearance of insulin positive cells in the islets while, CD 105
      positive cells remained in the adipose tissue. After 5 and 10 months from the
      onset of diabetes, rat pancreas showed, well developed larger sized islets with
      disappearance of primitive cell collections and CD 105 positive cells. Also,
      insulin positive islets of variable size with disappearance of insulin positive
      cells in adipose tissue were detected. CONCLUSION: The NCD possesses antidiabetic
      actions and enhanced pancreatic islets regeneration.

PMID- 24279647
TI  - Evidence for bilateral endolymphatic hydrops in ipsilateral delayed endolymphatic
      hydrops: preliminary results from examination of five cases.
AB  - CONCLUSION: After the administration of a standard dose of gadodiamide, an
      intravenous gadolinium-based contrast agent (GBCA), magnetic resonance imaging
      (MRI) evaluation of endolymphatic hydrops (EH) became possible in patients with
      ipsilateral delayed endolymphatic hydrops (DEH). We found that patients with
      ipsilateral DEH may also have bilateral EH. OBJECTIVE: MRI evaluation contributes
      to understanding of the pathological conditions in patients with EH. However,
      double or triple the standard dose of GBCA is often required to obtain images of
      high quality. We attempted to examine EH bilaterally in patients with ipsilateral
      DEH after routine administration of an intravenous GBCA. METHODS: GBCA
      (gadodiamide, 0.2 ml/kg) was administered intravenously to five patients with
      ipsilateral DEH. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR)
      MRI was performed with a 3-T MRI scanner 4 h after GBCA administration. RESULTS:
      In all five patients, EH was observed in the affected vestibules. Moreover, EH
      was observed bilaterally in four (80%) of five patients with ipsilateral DEH. The
      region of the deaf ear affected by EH was considerably larger compared with the
      normal ear in three patients. However, observed regions of EH were of
      approximately the same size in both ears in patients 4 and 5.

PMID- 24279648
TI  - Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1
      positive subject infected with a CRF11-cpx virus.
AB  - HIV drug resistance still represents a crucial problem in antiretroviral therapy.
      We report a case of a naive patient, harboring a CRF11-cpx virus, which showed
      drug resistance mutations in the reverse transcriptase. A drug resistance
      genotyping test was performed for the pol (protease, reverse transcriptase, and
      integrase) and V3 regions. The initial clinical parameter results showed a 4 log
      level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/MUl).
      We designed an initial highly active antiretroviral therapy (HAART) regimen
      including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus
      was highly resistant to all nucleoside and nucleotide reverse transcriptase
      inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs)
      except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all
      protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen
      including raltegravir (RAL)+DRV/r was started. Ten months later, the
      immunovirological status shows CD4(+) 142/MUl and HIV-RNA <37 cp/ml. Our results
      demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r
      in a patient infected with a complex X4-tropic CRF11-cpx virus.

PMID- 24279649
TI  - Nitric oxide impacts on angiotensin AT2 receptor modulation of high-pressure
      baroreflex control of renal sympathetic nerve activity in anaesthetized rats.
AB  - AIM: Nitric oxide (NO) interacts with the local brain renin-angiotensin system to
      modulate sympathetic outflow and cardiovascular homoeostasis. This study
      investigated whether NO influenced the ability of angiotensin AT2 receptor
      activation to modify the high-pressure baroreceptor regulation of renal
      sympathetic nerve activity (RSNA) and heart rate (HR). METHODS: Anaesthetized
      (chloralose/urethane) rats were prepared to allow generation of baroreflex gain
      curves for RSNA or HR following intracerebroventricular (I.C.V.) CGP42112 (AT2
      receptor agonist), PD123319 (AT2 receptor antagonist) or losartan (AT1 receptor
      antagonist), and then in combination with L-NAME (NO synthase inhibitor).
      RESULTS: I.C.V. PD123319, CGP42112, and Losartan did not change baseline mean
      arterial pressure, HR or RSNA. Baroreflex sensitivities for RSNA and HR were
      increased following AT2 receptor activation with CGP42112 by 112 and 157%,
      respectively, but were reduced following PD123319 by 20% (all P < 0.05). L-NAME
      alone increased baroreflex sensitivity for both RSNA and HR, by 62 and 158%,
      respectively, but when co-infused with either CGP42112 or PD123319, the
      baroreflex sensitivity fell to values comparable to those obtained during I.C.V.
      saline infusion. The baroreflex sensitivities for RSNA and HR were increased by
      losartan by 92% and 192%, respectively, but in the presence of L-NAME were no
      different from those obtained during I.C.V. saline infusion. CONCLUSION: There is
      an important facilitatory role for AT2 receptors in the high-pressure baroreflex
      regulation of RSNA and HR which is dependent on a functional NO/NOS system.
      Conversely, AT1 receptors have an inhibitory effect on the baroreflex, an action
      that relies on a tonic inhibition of NO.

PMID- 24279650
TI  - Healthcare professionals' acceptance of BelRAI, a web-based system enabling
      person-centred recording and data sharing across care settings with interRAI
      instruments: a UTAUT analysis.
AB  - BACKGROUND: Healthcare and social care environments are increasingly confronted
      with older persons with long-term care needs. Consequently, the need for
      integrated and coordinated assessment systems increases. In Belgium, feasibility
      studies have been conducted on the implementation and use of interRAI instruments
      offering opportunities to improve continuity and quality of care. However, the
      development and implementation of information technology to support a shared
      dataset is a difficult and gradual process. We explore the applicability of the
      UTAUT theoretical model in the BelRAI healthcare project to analyse the
      acceptance of the BelRAI web application by healthcare professionals in home
      care, nursing home care and acute hospital care for older people with
      disabilities. METHODS: A structured questionnaire containing items based on
      constructs validated in the original UTAUT study was distributed to 661 Flemish
      caregivers. We performed a complete case analysis using data from 282
      questionnaires to obtain information regarding the effects of performance
      expectancy (PE), effort expectancy (EE), social influence (SI), facilitating
      conditions (FC), anxiety (ANX), self-efficacy (SE) and attitude towards using
      technology (ATUT) on behavioural intention (BI) to use the BelRAI web
      application. RESULTS: The values of the internal consistency evaluation of each
      construct demonstrated adequate reliability of the survey instrument. Convergent
      and discriminant validity were established. However, the items of the ATUT
      construct cross-loaded on PE. FC proved to have the most significant influence on
      BI to use BelRAI, followed by SE. Other constructs (PE, EE, SI, ANX, ATUT) had no
      significant influence on BI. The 'direct effects only' model explained 30.8% of
      the variance in BI to use BelRAI. CONCLUSIONS: Critical factors in stimulating
      the behavioural intention to use new technology are good-quality software,
      interoperability and compatibility with other information systems, easy access to
      computers, training facilities, built-in and online help and ongoing IT support.
      These findings can be used by policy makers to maximise the acceptance and the
      success of new technology. For researchers, the conclusions of the original UTAUT
      study with regards to the item and scale construction should not be copied
      blindly across different information systems. A bottom-up approach is preferred
      when building upon the UTAUT model.

PMID- 24279651
TI  - Local structure of Ba(1-x)Sr(x)TiO3 and BaTi(1-y)Zr(y)O3 nanocrystals probed by X
      ray absorption and X-ray total scattering.
AB  - The effect of isovalent chemical substitution on the magnitude and coherence
      length of local ferroelectric distortions present in sub-20 nm Ba(1-x)Sr(x)TiO3
      (x = 0.0, 0.30, 0.50, 1.0) and BaTi(1-y)Zr(y)O3 (y = 0.0, 0.15, 0.50, 1.0)
      nanocrystals synthesized at room temperature is investigated using X-ray
      absorption near edge structure (XANES) and pair distribution function analysis of
      X-ray total scattering data (PDF). Although the average crystal structure of the
      nanocrystals is adequately described by a centrosymmetric, cubic Pm3m space
      group, local ferroelectric distortions due to the displacement of the titanium
      atom from the center of the perovskite lattice are observed for all compositions,
      except BaZrO3. The symmetry of the ferroelectric distortions is adequately
      described by a tetragonal P4mm space group. The magnitude of the local
      displacements of the titanium atom in BaTiO3 nanocrystals is comparable to that
      observed in single crystals and bulk ceramics, but the coherence length of their
      ferroelectric coupling is much shorter (<=20 A). Substitution of Sr(2+) for
      Ba(2+) and of Zr(4+) for Ti(4+) induces a tetragonal-to-cubic transition of the
      room temperature local crystal structure, analogous to that observed for single
      crystals and bulk ceramics at similar compositions. This transition is driven by
      a reduction of the magnitude of the local displacements of the titanium atom
      and/or of the coherence length of their ferroelectric coupling. Replacing 50% of
      Ba(2+) with Sr(2+) slightly reduces the magnitude of the titanium displacement,
      but the coherence length is not affected. In contrast, replacing 15% of the
      ferroelectrically active Ti(4+) with Zr(4+) leads to a significant reduction of
      the coherence length. Deviations from the ideal solid solution behavior are
      observed in BaTi(1-y)Zr(y)O3 nanocrystals and are attributed to an inhomogeneous
      distribution of the barium atoms in the nanocrystal. Composition-structure
      relationships derived for Ba(1-x)Sr(x)TiO3 and BaTi(1-y)Zr(y)O3 nanocrystals
      demonstrate that the evolution of the room temperature local crystal structure
      with chemical composition parallels that of single crystals and bulk ceramics,
      and that chemical control over ferroelectric distortions is possible in the sub
      20 nm size range. In addition, the potential of PDF analysis of total scattering
      data to probe compositional fluctuations in nanocrystals is demonstrated.

PMID- 24279653
TI  - Incidence of canal systems in the mesio-buccal roots of maxillary first and
      second molars in Saudi Arabian population.
AB  - The aim of this prospective study was to determine the number of canals treated
      in the mesio-buccal roots of the maxillary first and second molars teeth of a
      Saudi Arabian population during a 1-year period in a postgraduate endodontic
      program. The attending endodontic faculty member supervising the case verified
      the number of canals in the teeth clinically and radiographically. In total, 308
      maxillary first molars and 162 maxillary second molars, of which 158 (51.3%) and
      32 (19.7%) met the criterion of having two canals detected and treated in the
      mesio-buccal root of the maxillary first and second molars, respectively. It was
      concluded that the occurrence of mesio-palatal canal in the mesio-buccal root of
      the maxillary first and second molars of a Saudi Arabian population was high. The
      fact that almost more than half the mesio-buccal roots of the maxillary first
      molars bear two canals is enough reason to always assume that two canals exist
      until careful examination proves otherwise. 

PMID- 24279654
TI  - Push-out bond strength of gutta-percha with a new bioceramic sealer in the
      presence or absence of smear layer.
AB  - The purpose of this study was to compare the bond strength of a new bioceramic
      sealer (EndoSequence BC Sealer) and AH Plus in the presence or absence of smear
      layer. Extracted single-rooted human teeth were prepared and randomly divided
      into four groups. In groups 1 and 3, the root canals were finally irrigated with
      5.25% NaOCl and smear layer was not removed, but in groups 2 and 4, the root
      canals were finally irrigated with 17% EDTA followed by 5.25% NaOCl in order to
      remove the smear layer. In groups 1 and 2, the root canals were obturated with
      gutta-percha/AH Plus, but in groups 3 and 4, obturation was performed with gutta
      percha/EndoSequence BC Sealer. Push-out bond strength and failure modes were
      evaluated. The bond strength of gutta-percha/AH Plus and gutta
      percha/EndoSequence BC Sealer was not significantly different (P = 0.89). The
      presence or absence of smear layer did not significantly affect the bond strength
      of filling materials (P = 0.69). The mode of bond failure was mainly cohesive for
      all groups. In conclusion, the bond strength of the new bioceramic sealer was
      equal to that of AH Plus with or without the smear layer. 

PMID- 24279656
TI  - Effect of chloroform, orange solvent and eucalyptol on the accuracy of four
      electronic apex locators.
AB  - The aim of this study was to evaluate the effect of three retreatment solutions
      on the accuracy of four electronic apex locators, the Root ZX mini, the Mini Apex
      Locator, the Root ZX and the Elements Diagnostic Unit and Apex Locator. Forty
      extracted single-rooted human teeth were used in this study. The four electronic
      apex locators were operated according to the manufacturer's instructions to
      locate the 'apical constriction' in the presence of chloroform, orange solvent or
      eucalyptol in the canal. The accuracy of each apex locator was not affected by
      the type of retreatment solution present in the root canal. In addition, the
      accuracy of the four apex locators was similar in the presence of each of the
      tested solutions. 

PMID- 24279655
TI  - Evaluation of the colour change in enamel and dentine promoted by the interaction
      between 2% chlorhexidine and auxiliary chemical solutions.
AB  - To evaluate the colour change in enamel and dentine, promoted by interaction of
      2% chlorhexidine gluconate (CHX) with 5.25% sodium hypochlorite (NaOCl) and 17%
      ethylenediaminetetraacetic acid (EDTA). Fragments containing enamel and dentine
      were obtained from the crowns of extracted bovine incisors. Before and after
      immersion of the samples in the substances, they were evaluated with reference to
      the colour of the enamel and dentine. The values obtained in numerical scores
      were subjected to statistical analysis using Wilcoxon test. A colour change in
      the enamel and dentine in groups treated with CHX gel + NaOCl and CHX gel + NaOCl
      + EDTA, and a change in colour only in the dentine in groups treated with CHX
      solution + NaOCl and CHX solution + NaOCl + EDTA. When used prior to NaOCl, CHX
      has the ability to induce a colour change in dental structures. 

PMID- 24279657
TI  - Comparison of final irrigation techniques in removal of calcium hydroxide.
AB  - The aim of this study was to compare new irrigation systems with a conventional
      irrigation technique for the removal of inter-appointment calcium hydroxide
      [Ca(OH)2 ]. Forty-seven extracted human single-rooted teeth were instrumented,
      and Ca(OH)2 paste was placed into root canals by using a lentulo spiral at the
      apical third. Teeth were randomly divided into three groups according to
      different irrigation protocols using a 30-gauge slot-tipped needle, EndoVac
      system and ProUltra(r) PiezoFlowTM ultrasonic irrigation system. Scanning
      electron microscopic images of the selected root canal surfaces (cervical, middle
      and apical third) were evaluated using a 5-grade scale. The influence of the
      irrigation system was evaluated using a two-way analysis of variance test and
      Tukey's test. The EndoVac and PiezoFlow groups demonstrated the lowest scale
      values (cleanest canals); however, there was no statistical difference between
      these two groups. The conventional irrigation group exhibited significantly
      higher scores (P < 0.05). The conventional needle irrigation was not sufficient
      to remove Ca(OH)2 from the root canal system. Irrigation with EndoVac and
      PiezoFlowTM ultrasonic irrigation systems improved the removal of the intracanal
      medicament resulting in cleaner root canal walls. 

PMID- 24279658
TI  - Influence of silane and solvated bonding agents on the bond strength to glass
      fibre posts.
AB  - The combined use of silane and solvated bonding agents on the bond strength to
      glass-fibre posts was investigated. A model Bis-GMA/HEMA adhesive was formulated
      with no solvent, 30% of ethanol or 80% of acetone. The surfaces of rectangular
      shaped posts were silanated or not and one of the agents was applied, except for
      the control group. Cylinders of resin cement (RelyX ARC, 3M ESPE, Saint Paul, MN,
      USA) were built-up on the surfaces (n = 20) and submitted to shear testing. All
      groups showed higher bond strengths when the surfaces were silanated. When no
      silanization was carried out, the use of bonding agents, either solvated or non
      solvated, increased the bond strengths. All groups treated with both silane and
      bonding agent showed higher bond strengths than the group that was only
      silanated. Control and ethanol-based adhesives were similar, whereas the acetone
      based agent yielded higher bond strengths. Adhesive failures were predominant.
      Combination of silane and adhesive enhanced the bond to fibre posts. 

PMID- 24279659
TI  - Analysis of six heavy metals in Ortho mineral trioxide aggregate and ProRoot
      mineral trioxide aggregate by inductively coupled plasma-optical emission
      spectrometry.
AB  - Ortho mineral trioxide aggregate (MTA) is a mineral aggregate newly developed for
      perforation repair, root end filling and pulp capping. The aim of this study was
      to investigate the levels of cadmium (Cd), copper (Cu), iron (Fe), manganese
      (Mn), nickel (Ni) and zinc (Zn) in Ortho MTA and ProRoot MTA. A total of 0.2 g of
      each MTA was digested using a mixture of hydrochloric and nitric acids and
      filtered. Six heavy metals in the resulting filtrates were analyzed by
      inductively coupled plasma-optical emission spectrometry (n = 5). The results
      were statistically analyzed using the Mann-Whitney U-test. The concentrations of
      Cd, Cu, Fe, Mn, Ni and Zn in Ortho MTA were 0.10, 7.73, 49.51, 2.58, 0.82 and
      10.09 p.p.m., respectively. The concentrations of Cd, Cu, Fe, Mn, Ni and Zn in
      ProRoot MTA were 0.16, 9.38, 1438.11, 74.51, 18.98 and 4.05 p.p.m., respectively.
      In conclusion, Ortho MTA had lower levels of Cd, Cu, Fe, Mn and Ni than ProRoot
      MTA. 

PMID- 24279660
TI  - Effect of manual dynamic activation on smear layer removal efficacy of
      ethylenediaminetetraacetic acid and SmearClear: an in vitro scanning electron
      microscopic study.
AB  - The purpose of the present study was to evaluate the effect of manual dynamic
      activation (MDA) with a master gutta-percha point on the smear layer removal
      efficacy of 17% ethylenediaminetetraacetic acid (EDTA) and SmearClear. Fifty
      freshly extracted human single-rooted teeth were prepared using ProTaper rotary
      system up to F3 size. The prepared teeth were divided into five groups on the
      basis of final irrigation received. Group A: 3% NaOCl solution (negative control
      group). Group B: 5 mL of 17% EDTA. Group C: 1 mL of 17% EDTA + MDA for 2 min + 4
      mL of 17% EDTA rinse. Group D: 5 mL of SmearClear. Group E: 1 mL of SmearClear +
      MDA for 2 min + 4 mL of SmearClear rinse. Prepared samples were decoronated and
      then longitudinally split into two halves and evaluated under scanning electron
      microscope. Representative images at coronal, middle and apical third level were
      taken and scored for the amount of smear layer present, using a three-score
      system. The data were analysed through Kruskal-Wallis and Mann-Whitney U-test.
      The root canal surfaces of samples of group C and group E (where MDA was done)
      were significantly cleaner in apical third regions than those of group B and
      group D (P < 0.05). 

PMID- 24279661
TI  - Behaviour of rat-cultured dental pulp cells in three-dimensional collagen type-1
      gel in vitro and in vivo.
AB  - The purpose of this study was to investigate the growth and differentiation
      potential of dental pulp cells (DPCs) in three-dimensional (3-D) collagen type-1
      scaffold in vitro and in vivo. Third passage DPCs were cultured in a 3-D collagen
      and expression of both bone- or dentin-related mRNA (alkaline phosphatase (ALP),
      bone sialoprotein (BSP) and osteopontin (OPN)) and morphological changes
      evaluated in vitro. In the in vivo study, two types of grafts were transplanted
      into the rectus abdominus muscles of rats and harvested after 7 days: DPCs in
      alpha-minimal essential medium and DPCs mixed with a collagen gel. ALP, BSP and
      OPN were used as primary antibodies for immunohistochemical study. Histological
      and immunohistochemical results showed that DPCs in collagen gel were spindle
      shaped and showed significantly greater expression of ALP, BSP and OPN in vitro
      than the controls. Transplanted DPCs in collagen type-1 gel showed greater
      positive immunoreactivity for ALP, BSP and OPN than the controls. It was
      concluded that the collagen gel scaffold encouraged the differentiation of DPCs
      into osteoblastic cells. 

PMID- 24279662
TI  - Effect of reciprocation usage of nickel-titanium rotary files on the cyclic
      fatigue resistance.
AB  - The use of reciprocating motion for a nickel-titanium file has been claimed to
      increase its resistance to fatigue in comparison to continuous rotation. The
      purpose of this study was to investigate the effect using a reciprocating motion
      instead of continuous rotation for nickel-titanium files on their cyclic fatigue
      resistance. Cyclic fatigue tests simulating clinical use with ProTaper F2 and
      ProFile #25/.06 instruments were carried out in an artificial stainless-steel
      root canal with a 1.5 mm inner diameter, 5 mm radius and 60 degrees  angle of
      curvature. The instruments were driven using either continuous rotation or
      reciprocation until fracture. For the reciprocation, the rotation angles were set
      to 140 degrees  clockwise and 45 degrees  counterclockwise. The number of cycles
      to fracture was determined by measuring the time to fracture. Statistical
      analysis was performed using two-way anova. There were no significant differences
      in the fracture cycles due to the use of reciprocation or continuous rotation for
      either instrument. The results found using reciprocation were comparable to those
      found using continuous rotation with regard to the cyclic fatigue resistance of
      nickel-titanium rotary files. 

PMID- 24279663
TI  - Cyclic fatigue resistance of newly manufactured rotary nickel titanium
      instruments used in different rotational directions.
AB  - The aim of this study was to investigate whether cyclic fatigue resistance is
      increased for nickel titanium instruments manufactured with improved heating
      processes in clockwise or counterclockwise continuous rotation. The instruments
      compared were produced either using the R-phase heat treatment (K3XF; SybronEndo,
      Orange, CA, USA) or the M-wire alloy (ProFile Vortex; DENTSPLY Tulsa Dental
      Specialties, Tulsa, OK, USA). Tests were performed with a specific cyclic fatigue
      device that evaluated cycles to failure of rotary instruments in curved
      artificial canals. Results indicated no significant difference in resistance to
      cyclic fatigue when rotary nickel titanium instruments are used in clockwise or
      counterclockwise continuous rotation. In both directions of rotation, size 04-25
      K3XF showed a significant increase (P < 0.05) in the mean number of cycles to
      failure when compared with size 04-25 ProFile Vortex. 

PMID- 24279664
TI  - Evaluation of alginate as a substitute for root-surrounding tissues in electronic
      root canal measurements.
AB  - Alginate as a substitute for root-surrounding tissue was investigated. The
      electronic working lengths of root canals under clinical conditions were compared
      with an in vitro simulation of the same teeth extracted and embedded in alginate.
      The working lengths in 26 teeth were determined on two occasions using an
      electronic apex locator, before extraction and after extraction with the same
      teeth embedded in an alginate mass. The apical 4 mm of the root canals were
      exposed following the measurements, and the distances between the apical
      constrictions and the tips of files repositioned in the canals were measured and
      recorded. The mean distance between the file tip and the constriction was +0.33
      mm (+/-0.38) in vivo and +0.32 mm (+/-0.30) in vitro. The Wilcoxon signed-rank
      test indicated that these means were not significantly different. The apical
      constriction was assessed to be within the limits of 0.5 mm in 80.7% of in vivo
      cases and in 76.9% of extracted teeth. Statistical analysis demonstrated that
      there was no significant difference between the results recorded in vivo and in
      vitro regarding apical constriction localisation. Based on the results of this
      study, the alginate mass is a useful tool in evaluating the performance of
      electronic apex locators. 

PMID- 24279665
TI  - Ultramicroscopic study of the interface and sealing ability of four root canal
      obturation methods: Resilon versus gutta-percha.
AB  - Recently, filling materials have been introduced based on the dentine adhesion
      technologies used in conservative dentistry in an attempt to seal the root canal
      more effectively. The purpose of this study was to investigate the interface
      between the canal and root-filling material. Sealing ability of four root canal
      obturation methods was analysed by means of scanning electron microscopy.
      Extracted single-rooted teeth were endodontically treated and filled with gutta
      percha/Pulp Canal Sealer using the Thermafil (TH) technique, gutta-percha/Pulp
      Canal Sealer using the System B (SB) technique, Resilon points/RealSeal (RS) and
      RealSeal 1/RealSeal (RS1). Specimen interfaces were analysed using field-emission
      scanning electron microscopy. The adhesive groups RS and RS1, formed hybrid
      layers but showed areas of separation (gaps) similar to those in the conventional
      obturation groups. The RS and RS1 groups showed less separation in the coronal
      third, but the separation was similar to that in the TH and SB groups in the
      middle and apical thirds. The sealing ability of Resilon is not superior to that
      of existing materials. 

PMID- 24279666
TI  - Kinetics of Th17-related cytokine expression in experimentally induced rat
      periapical lesions.
AB  - Th17-related cytokines are essential factors in various pathological states,
      including inflammatory bone destruction. This study investigated the contribution
      of Th17-related cytokines to the progress of experimentally induced rat
      periapical lesions. Periapical pathoses were induced by unsealed exposure of the
      pulp chamber of the lower first molars. A variety of immunocompetent cells,
      including CD68(+) macrophages, Ia antigen(+) cells and TCRalphabeta(+) T cells,
      were observed in the lesions. The expression levels of Th17-related cytokines, IL
      17 and IL-23, and of pro-inflammatory cytokines, IL-1beta and IL-6, were
      significantly increased at 14 days (expansion stage) compared with normal
      periapical tissues. The expression levels of Foxp3, a regulatory T cell (Treg)
      related gene, and of IL-10, an anti-inflammatory cytokine, were higher at 28 days
      (chronic stage) than at 14 days. These findings suggest that Th17-related
      cytokines may be primary contributors to the initiation of periapical bone
      destruction, and that lesion expansion may be regulated by anti-inflammatory
      mediators. 

PMID- 24279667
TI  - Efficacy of the enamel matrix derivative in direct pulp capping procedures: a
      systematic review.
AB  - The aim was to review the efficacy of the enamel matrix derivative (EMD) in
      direct pulp capping (DPC) procedures. Databases were explored using the following
      keywords: 'dental', 'dentine', 'enamel matrix derivative', 'pulp capping' and
      'treatment'. The inclusion criteria were: (i) original studies; (ii) human and
      animal studies; (iii) reference list of potentially relevant original and review
      articles; (iv) intervention: effect of EMD on pulp-capping procedures; and (v)
      articles published only in English. Eight studies (four human and four animal)
      were included. Among the human studies, two studies reported that EMD is a more
      efficient DPC procedure compared with calcium hydroxide (Ca(OH)2 ). One study
      reported Ca(OH)2 to be more efficient for DPC than EMD. One study reported no
      difference in the efficacies between EMD and Ca(OH)2 for DPC. All animal studies
      reported EMD to be more effective in reparative dentine formation in comparison
      with Ca(OH)2 . EMD can provide favourable results in DPC procedures. 

PMID- 24279668
TI  - Florid cemento-osseous dysplasia mimicking apical periodontitis: A case report.
AB  - Cemento-osseous dysplasia may present as a focal, periapical or florid lesion in
      the mandible or maxilla. The lesion may sometimes appear similar to peri
      radicular lesions on a periapical radiograph. This report presents a case with
      irreversible pulpitis and root resorption as well as a mixed
      radiolucent/radiopaque lesion around a mandibular molar tooth root. Root canal
      treatment was performed and because of the radiographic signs of root resorption
      and the patient's fear of having a malignant disease, periapical surgery was also
      performed. The histopathology report confirmed the presence of florid cement
      osseous dysplasia which was mimicking apical periodontitis. Follow-up radiography
      12 months after the surgery illustrated complete healing of the radiolucent area.

PMID- 24279670
TI  - Launching the 18th Scientific Congress of Asian Pacific Endodontic Confederation
      (APEC) and 4th Jordanian Endodontic Conference in ESE, Lisbon.

PMID- 24279671
TI  - Report on the European Society of Endodontology meeting in Lisbon, Portugal, 12
      14 September 2013.

PMID- 24279674
TI  - Long-term elimination of hepatitis C virus from human hepatocyte chimeric mice
      after interferon-gamma gene transfer.
AB  - Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, liver
      failure, and hepatocellular carcinoma. Although the combination therapy employing
      pegylated interferon (IFN)-alpha and ribavirin is effective, this treatment is
      effective in only approximately 50% patients with genotype 1 HCV infection. IFN
      gamma is a potent anti-HCV agent that exhibits its antiviral action through a
      receptor distinct from that for IFN-alpha. Therefore, IFN-gamma application might
      provide an alternative approach to IFN-alpha-based therapies. However,
      recombinant IFN-gamma protein exhibits a poor pharmacokinetic property, that is,
      a very short half-life. It is our hypothesis that sustained IFN-gamma serum
      concentrations produced by gene transfer could effectively eliminate HCV in vivo.
      We examined the in vivo antiviral activity in human hepatocyte chimeric mice
      infected with genotype 1b HCV at high HCV RNA titers (10(5)-10(7) copies/ml). The
      human IFN-gamma-expressing plasmid vector pCpG-huIFNgamma exhibited prolonged
      transgene expression in mice compared with the plasmid vector pCMV-huIFNgamma.
      Moreover, the gene transfer of pCpG-huIFNgamma eliminated HCV from the liver of
      the chimeric mice for a sustained period. On the contrary, administration of pCMV
      huIFNgamma could not eliminate HCV. In conclusion, we found that a single pCpG
      huIFNgamma injection resulted in long-term elimination of HCV RNA in chimeric
      mice, providing, for the first time, direct evidence that chronic infection with
      high titer HCV in vivo can be treated by sustained IFN-gamma treatment.

PMID- 24279675
TI  - More than royal food - Major royal jelly protein genes in sexuals and workers of
      the honeybee Apis mellifera.
AB  - BACKGROUND: In the honeybee Apis mellifera, female larvae destined to become a
      queen are fed with royal jelly, a secretion of the hypopharyngeal glands of young
      nurse bees that rear the brood. The protein moiety of royal jelly comprises
      mostly major royal jelly proteins (MRJPs) of which the coding genes (mrjp1-9)
      have been identified on chromosome 11 in the honeybee's genome. RESULTS: We
      determined the expression of mrjp1-9 among the honeybee worker caste (nurses,
      foragers) and the sexuals (queens (unmated, mated) and drones) in various body
      parts (head, thorax, abdomen). Specific mrjp expression was not only found in
      brood rearing nurse bees, but also in foragers and the sexuals. CONCLUSIONS: The
      expression of mrjp1 to 7 is characteristic for the heads of worker bees, with an
      elevated expression of mrjp1-4 and 7 in nurse bees compared to foragers. Mrjp5
      and 6 were higher in foragers compared to nurses suggesting functions in addition
      to those of brood food proteins. Furthermore, the expression of mrjp9 was high in
      the heads, thoraces and abdomen of almost all female bees, suggesting a function
      irrespective of body section. This completely different expression profile
      suggests mrjp9 to code for the most ancestral major royal jelly protein of the
      honeybee.

PMID- 24279677
TI  - Pharmacoeconomic evaluation of voriconazole vs. liposomal amphotericin B in
      empiric treatment of invasive fungal infections in Turkey.
AB  - BACKGROUND: Invasive fungal infections (IFI) are associated with considerable
      expense and mortality on healthcare systems. There is a need to provide evidence
      of both clinical efficacy and value for money with any health technology. The
      current pharmacoeconomic evaluation investigated the use of liposomal
      amphotericin B (LAmB) and voriconazole for the empiric treatment of IFI in the
      Turkish setting. METHODS: Decision analytic modelling was used to create a
      pathway for patient treatment with a 5-point composite outcome measure. The data
      was obtained from a major non-inferiority multicentre randomised controlled
      study, with an expert panel of clinicians in Turkey providing transition
      probabilities and cost not available in the literature. Sensitivity analyses were
      performed on the inputs from the clinical trial and the expert panel. RESULTS: As
      per the base case analysis, voriconazole was preferred by Turkish Lira (TL) 2,523
      per patient treated and TL2,520 per surviving patient. LAmB was the preferred
      alternative by TL5,362 per successfully treated patient. Removing fever
      resolution as part of the composite outcome measure resulted in voriconazole
      being the preferred alternative per successfully treated patient. Univariate
      sensitivity analysis highlighted that increasing the duration of voriconazole by
      >1.2 days or decreasing LAmB by >1.0 days changes the result. Monte Carlo
      Simulation resulted in 69.4% of simulations favouring voriconazole per patient
      treated. CONCLUSION: There is a strong likelihood that voriconazole is
      economically more favourable than LAmB in the empiric treatment of IFI in Turkey.

PMID- 24279678
TI  - Relationship of trait anger and anger expression to C-reactive protein in
      postmenopausal women.
AB  - Coronary heart disease (CHD) is the leading cause of death for women worldwide.
      Chronic inflammation and risk factors, such as obesity, smoking, and high
      cholesterol, are well-established risk factors for CHD. Little is known, however,
      about the mechanisms by which psychosocial factors, such as general anger
      proneness (trait anger) and anger expression style, may be associated with
      proinflammatory processes that contribute to cardiovascular morbidity and
      mortality in women. Our purpose in conducting this study was to examine the
      relationship of trait anger and anger expression to the proinflammatory biomarker
      C-reactive protein (CRP). A cross-sectional between-groups design was used to
      determine differences in serum levels of CRP in 42 American postmenopausal women,
      ages 45 to 65, who scored high on the selected anger characteristics, compared
      with women with lower scores. We did not find differences between high anger
      women and low anger women in mean levels of CRP, but we did find significant
      inverse relationships between CRP and some anger control characteristics.
      Specific health-promoting anger coping behaviors could minimize the deleterious
      effects of inflammatory responses in postmenopausal women. 

PMID- 24279679
TI  - MALDI imaging mass spectrometry in glomerulonephritis: feasibility study.
AB  - AIMS: The in-situ proteomics technology known as matrix-assisted laser
      desorption/ionization imaging mass spectrometry (MALDI-IMS) is a powerful
      technique that combines traditional histology and proteomics. METHODS AND
      RESULTS: MALDI-IMS was applied to routine diagnostic kidney biopsies in a small
      group of cases of membranous glomerulonephritis and minimal change disease.
      Molecular changes were observed not only in the tissue areas with pathological
      alterations, but also in morphologically normal-looking tissue, highlighting the
      potential feasibility of using MALDI-IMS as a tool in nephropathology.
      CONCLUSIONS: This technology can be applied to any biopsy where a frozen section
      is obtained as part of the diagnostic process. Although we do not yet know the
      molecular identity of the differentially expressed proteins/peptides, they could
      represent powerful classifiers of nosological groups.

PMID- 24279676
TI  - Matrix regulation of idiopathic pulmonary fibrosis: the role of enzymes.
AB  - Repairing damaged tissues is an essential homeostatic mechanism that enables
      clearance of dead or damaged cells after injury, and the maintenance of tissue
      integrity. However, exaggeration of this process in the lung can lead to the
      development of fibrotic scar tissue. This is characterized by excessive
      accumulation of extracellular matrix (ECM) components such as fibronectin,
      proteoglycans, hyaluronic acid, and interstitial collagens. After tissue injury,
      or a breakdown of tissue integrity, a cascade of events unfolds to maintain
      normal tissue homeostasis. Inflammatory mediators are released from injured
      epithelium, leading to both platelet activation and inflammatory cell migration.
      Inflammatory cells are capable of releasing multiple pro-inflammatory and
      fibrogenic mediators such as transforming growth factor (TGF)beta and interleukin
      (IL)-13, which can trigger myofibroblast proliferation and recruitment. The
      myofibroblast population is also expanded as a result of epithelial cells
      undergoing epithelial-to-mesenchymal transition and of the activation of resident
      fibroblasts, leading to ECM deposition and tissue remodeling. In the healthy
      lung, wound healing then proceeds to restore the normal architecture of the lung;
      however, fibrosis can develop when the wound is severe, the tissue injury
      persists, or the repair process becomes dysregulated. Understanding the processes
      regulating aberrant wound healing and the matrix in the chronic fibrotic lung
      disease idiopathic pulmonary fibrosis (IPF), is key to identifying new treatments
      for this chronic debilitating disease. This review focuses primarily on the
      emerging role of enzymes in the lungs of patients with IPF. Elevated expression
      of a number of enzymes that can directly modulate the ECM has been reported, and
      recent data indicates that modulating the activity of these enzymes can have a
      downstream effect on fibrotic tissue remodeling. 

PMID- 24279680
TI  - Chemoinformatic characterization of activity and selectivity switches of
      antiprotozoal compounds.
AB  - BACKGROUND: Benzimidazole derivatives are promising compounds for the treatment
      of parasitic infections. The structure-activity relationships of 91
      benzimidazoles with activity against Trichomonas vaginalis and Giardia
      intestinalis were analyzed using a novel activity landscape modeling approach.
      RESULTS: We identified two prominent cases of 'activity switches' and
      'selectivity switches' where two R group substitutions in the benzimidazole
      scaffold completely invert the activity and selectivity pattern for T. vaginalis
      and G. intestinalis. CONCLUSION: A chemoinformatic methodology was used to
      rapidly identify discrete structural changes around the central scaffold that are
      associated with large changes in biological activity for each parasite. The
      structure-activity relationships for the benzimidazole derivatives is smooth for
      both protozoan with few but markedly important activity cliffs.

PMID- 24279681
TI  - A novel plant-fungus symbiosis benefits the host without forming mycorrhizal
      structures.
AB  - * Most terrestrial plants form mutually beneficial symbioses with specific soil
      borne fungi known as mycorrhiza. In a typical mycorrhizal association, fungal
      hyphae colonize plant roots, explore the soil beyond the rhizosphere and provide
      host plants with nutrients that might be chemically or physically inaccessible to
      root systems. * Here, we combined nutritional, radioisotopic ((33)P) and genetic
      approaches to describe a plant growth promoting symbiosis between the
      basidiomycete fungus Austroboletus occidentalis and jarrah (Eucalyptus
      marginata), which has quite different characteristics. * We show that the fungal
      partner does not colonize plant roots; hyphae are localized to the rhizosphere
      soil and vicinity and consequently do not transfer nutrients located beyond the
      rhizosphere. Transcript profiling of two high-affinity phosphate (Pi) transporter
      genes (EmPHT1;1 and EmPHT1;2) and hyphal-mediated (33)Pi uptake suggest that the
      Pi uptake shifts from an epidermal to a hyphal pathway in ectomycorrhizal plants
      (Scleroderma sp.), similar to arbuscular mycorrhizal symbioses, whereas A.
      occidentalis benefits its host indirectly. The enhanced rhizosphere carboxylates
      are linked to growth and nutritional benefits in the novel symbiosis. * This work
      is a starting point for detailed mechanistic studies on other basidiomycete-woody
      plant relationships, where a continuum between heterotrophic rhizosphere fungi
      and plant beneficial symbioses is likely to exist.

PMID- 24279682
TI  - Neurotology symptoms at referral to vestibular evaluation.
AB  - BACKGROUND: Dizziness-vertigo is common in adults, but clinical providers may
      rarely diagnose vestibular impairment and referral could be delayed. To assess
      neurotology symptoms (including triggers) reported by patients with peripheral
      vestibular disease, during the year just before their referral to vestibular
      evaluation. METHODS: 282 patients with peripheral vestibular disease and 282
      control subjects accepted to participate. They had no middle ear, retinal,
      neurological, psychiatric, autoimmune or autonomic disorders. They reported their
      symptoms by a standardized questionnaire along with their anxiety/depression
      symptoms. RESULTS: Patients were referred after months or years from the onset of
      their symptoms, 24% of them reported frequent falls with a long clinical
      evolution; 10% of them reported no vertigo but instability related to specific
      triggers; 86% patients and 12% control subjects reported instability when moving
      the head rapidly and 79% patients and 6% control subjects reported instability
      when changing posture. Seven out of the 9 symptoms explored by the questionnaire
      allowed the correct classification of circa 95% of the participants (Discriminant
      function analysis, p < 0.001). High blood pressure, dyslipidemia and
      anxiety/depression symptoms showed a mild correlation with the total score of
      symptoms (multiple R2 =0.18, p < 0.001). CONCLUSIONS: Late referral to vestibular
      evaluation may underlie a history of frequent falls; some patients may not report
      vertigo, but instability related to specific triggers, which could be useful to
      prompt vestibular evaluation. High blood pressure, dyslipidemia and
      anxiety/depression symptoms may have a mild influence on the report of symptoms
      of vestibular disease in both, patients and control subjects.

PMID- 24279683
TI  - Isolation, screening and production studies of uricase producing bacteria from
      poultry sources.
AB  - Uricase (urate oxidase EC 1.7.3.3) is a therapeutic enzyme that is widely used to
      catalyze the enzymatic oxidation of uric acid in the treatment of hyperuricemia
      and gout diseases. In this study, three bacterial species capable of producing
      extracellular uricase were isolated from a poultry source and screened based on
      the size of the clear zone using a uric acid agar plate. The bacterial species
      capable of producing uricase with the highest uricolytic activity was identified
      as Bacillus cereus strain DL3 using a 16SrRNA gene sequencing approach. The time
      course study of uricase production was performed and the medium was optimized.
      Carboxymethylcellulose and asparagine were found to be the best carbon and
      nitrogen sources. Maximum uricolytic activity was observed at pH 7.0 with an
      inducer concentration of 2.0 g/L. Inoculum size of 5% gave maximum uricolytic
      activity. The maximum uricolytic activity of 15.43 U/mL was achieved at optimized
      conditions, which is 1.61 times more than the initial activity. Further,
      enzymatic stability was determined at different pH and temperature.

PMID- 24279684
TI  - Permanent neonatal diabetes in siblings with novel C109Y INS mutation transmitted
      by an unaffected parent with somatic mosaicism.
AB  - Mutations involving the insulin (INS) gene are a common cause of permanent
      neonatal diabetes (PND). Although INS mutations typically occur de novo and
      germline INS mutations transmitted to offspring by unaffected parents has been
      described, somatic mosaicism in a parent with an INS mutation has not been
      previously reported. We describe two siblings (one brother and one sister) with
      PND (26- and 19-yr old diagnosed at 3 and 7 months old, respectively), whose
      parents were unaffected. We performed genetic analysis of leukocyte DNA for this
      family. Both patients were found to carry the novel heterozygous c.326G>A
      substitution in exon 3 of INS, resulting in a p.C109Y change of the insulin
      protein. Analyses of leukocyte DNA from the parents revealed low level mutation
      in the sequencing trace of the father, raising the possibility of somatic
      mosaicism. Real-time polymerase chain reaction (PCR) analysis showed he had
      approximately 73% of the mutant allele relative to his affected son. This first
      report of somatic mosaicism in an unaffected parent with an INS mutation suggests
      that parental mosaicism may be responsible for the transmission of PND in
      patients with de novo INS mutations. As such, appropriate counseling for
      recurrent risks should be considered and we recommend that molecular genetic
      testing for future siblings at birth should be offered to the parents of children
      with INS mutation. 

PMID- 24279685
TI  - A randomized, controlled trial of everolimus-based dual immunosuppression versus
      standard of care in de novo kidney transplant recipients.
AB  - Kidney transplant recipients receiving calcineurin inhibitor-based
      immunosuppression incur increased long-term risks of cancer and kidney fibrosis.
      Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks.
      Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36
      month, prospective, multinational, open-label, randomized controlled trial for de
      novo kidney transplant recipients, assessed whether everolimus switch could
      enable elimination of mycophenolate plus either steroids or CNI without
      compromising efficacy. Patients received cyclosporin, mycophenolate and steroids
      for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI
      WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or
      cyclosporin, mycophenolate and steroids (control). 126 patients were randomized.
      The steroid WD arm was terminated prematurely because of excess discontinuations.
      Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1
      ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P=0.026).
      The CNI-WD group experienced a higher rate of BPAR(31% vs. control 13%, P=0.048)
      and showed a trend towards higher composite treatment failure (BPAR, graft loss,
      death, loss to follow-up). The 12 month results from SOCRATES show noninferiority
      in eGFR, but a significant excess of acute rejection when everolimus was
      commenced at week 2 to enable a progressive withdrawal of mycophenolate and
      cyclosporin in kidney transplant recipients.

PMID- 24279686
TI  - CONNECT for better fall prevention in nursing homes: results from a pilot
      intervention study.
AB  - OBJECTIVES: To determine whether an intervention that improves nursing home (NH)
      staff connections, communication, and problem solving (CONNECT) would improve
      implementation of a falls reduction education program (FALLS). DESIGN: Cluster
      randomized trial. SETTING: Community (n=4) and Veterans Affairs (VA) NHs (n=4).
      PARTICIPANTS: Staff in any role with resident contact (n=497). INTERVENTION: NHs
      received FALLS alone (control) or CONNECT followed by FALLS (intervention), each
      delivered over 3 months. CONNECT used storytelling, relationship mapping,
      mentoring, self-monitoring, and feedback to help staff identify communication
      gaps and practice interaction strategies. FALLS included group training, modules,
      teleconferences, academic detailing, and audit and feedback. MEASUREMENTS: NH
      staff completed surveys about interactions at baseline, 3 months (immediately
      after CONNECT or control period), and 6 months (immediately after FALLS). A
      random sample of resident charts was abstracted for fall risk reduction
      documentation (n=651). Change in facility fall rates was an exploratory outcome.
      Focus groups were conducted to explore changes in organizational learning.
      RESULTS: Significant improvements in staff perceptions of communication quality,
      participation in decision-making, safety climate, caregiving quality, and use of
      local interaction strategies were observed in intervention community NHs
      (treatment-by-time effect P=.01) but not in VA NHs, where a ceiling effect was
      observed. Fall risk reduction documentation did not change significantly, and the
      direction of change in individual facilities did not relate to observed direction
      of change in fall rates. Fall rates did not change in control facilities
      (falls/bed per year: baseline, 2.61; after intervention, 2.64) but decreased by
      12% in intervention facilities (falls/bed per year: baseline, 2.34; after
      intervention, 2.06); the effect of treatment on rate of change was 0.81 (95%
      confidence interval=0.55-1.20). CONCLUSION: CONNECT has the potential to improve
      care delivery in NHs, but the trend toward improving fall rates requires
      confirmation in a larger ongoing study.

PMID- 24279688
TI  - Electrochemical single-molecule detection in aqueous solution using self-aligned
      nanogap transducers.
AB  - Electrochemical detection of individual molecular tags in nanochannels may enable
      cost-effective, massively parallel analysis and diagnostics platforms. Here we
      demonstrate single-molecule detection of prototypical analytes in aqueous
      solution based on redox cycling in 40 nm nanogap transducers. These nanofluidic
      devices are fabricated using standard microfabrication techniques combined with a
      self-aligned approach that minimizes gap size and dead volume. We demonstrate the
      detection of three common redox mediators at physiological salt concentrations. 

PMID- 24279687
TI  - Brain networks shaping religious belief.
AB  - We previously demonstrated with functional magnetic resonance imaging (fMRI) that
      religious belief depends upon three cognitive dimensions, which can be mapped to
      specific brain regions. In the present study, we considered these co-activated
      regions as nodes of three networks each one corresponding to a particular
      dimension, corresponding to each dimension and examined the causal flow within
      and between these networks to address two important hypotheses that remained
      untested in our previous work. First, we hypothesized that regions involved in
      theory of mind (ToM) are located upstream the causal flow and drive non-ToM
      regions, in line with theories attributing religion to the evolution of ToM.
      Second, we hypothesized that differences in directional connectivity are
      associated with differences in religiosity. To test these hypotheses, we
      performed a multivariate Granger causality-based directional connectivity
      analysis of fMRI data to demonstrate the causal flow within religious belief
      related networks. Our results supported both hypotheses. Religious subjects
      preferentially activated a pathway from inferolateral to dorsomedial frontal
      cortex to monitor the intent and involvement of supernatural agents (SAs; intent
      related ToM). Perception of SAs engaged pathways involved in fear regulation and
      affective ToM. Religious beliefs are founded both on propositional statements for
      doctrine, but also on episodic memory and imagery. Beliefs based on doctrine
      engaged a pathway from Broca's to Wernicke's language areas. Beliefs related to
      everyday life experiences engaged pathways involved in imagery. Beliefs implying
      less involved SAs and evoking imagery activated a pathway from right lateral
      temporal to occipital regions. This pathway was more active in non-religious
      compared to religious subjects, suggesting greater difficulty and procedural
      demands for imagining and processing the intent of SAs. Insights gained by
      Granger connectivity analysis inform us about the causal binding of individual
      regions activated during religious belief processing.

PMID- 24279690
TI  - Dynamic Oil Consumption Measurement of Internal Combustion Engines using Laser
      Spectroscopy.
AB  - A new approach has been developed to measure dynamic consumption of lubricant oil
      in an internal combustion engine. It is based on the already known technique
      where sulfur is used as a natural tracer of the engine oil. Since ejection of
      motor oil in gaseous form into the exhaust is by far the main source of engine
      oil consumption, detection of sulfur in the exhaust emission is a valuable way to
      measure engine oil consumption in a dynamic way. In earlier approaches, this is
      done by converting all sulfur containing chemical components into SO2 by thermal
      pyrolysis in a high temperature furnace at atmospheric pressure. The so-formed
      SO2 then is detected by broadband-UV-induced fluorescence or mass spectrometric
      methods. The challenge is to reach the necessary detection limit of 50 ppb. The
      new approach presented here includes sulfur conversion in a low-pressure
      discharge cell and laser-induced fluorescence with wavelength and fluorescence
      lifetime selection. A limit of detection down to 10 ppb at a temporal resolution
      in the time scale of few seconds is reached. Extensive, promising studies have
      been performed at a real engine test bench. Future developments of a compact,
      mobile device based on these improvements are discussed. 

PMID- 24279691
TI  - Subcutaneous injection of diclofenac for the treatment of pain following minor
      orthopedic surgery (DIRECT study): a randomized trial.
AB  - OBJECTIVES: Parenteral diclofenac is frequently used for analgesia following
      minor orthopedic interventions. Currently available diclofenac formulations are
      for intramuscular (IM) or intravenous injection. A new 1 mL volume formulation of
      diclofenac containing hydroxypropyl-beta-cyclodextrin (HPbetaCD) allows both SC
      and IM administration. The objective of this open-label, randomized, parallel
      group, active-controlled study was to assess the safety and efficacy of 75 mg
      diclofenac HPbetaCD, administered SC or IM, compared with IM Voltaren(r) 75 mg in
      inpatients undergoing minor orthopedic surgeries with moderate-to-severe
      postoperative pain. METHODS: A total of 325 patients were randomized to
      treatment. Surgery-related pain was comparable between groups before treatment
      and rapidly declined in all patients following diclofenac injection. The primary
      endpoint was investigator-assessed local tolerability up to 18 hours
      postinjection (redness, swelling, and hardening at the injection site each scored
      on a 4-point scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe).
      RESULTS: Local tolerability was found to be optimal for all the injected
      formulations, with mean overall scores (0 to 9) of 0.57, 0.31, and 0.26, for
      diclofenac HPbetaCD SC, diclofenac HPbetaCD IM, and Voltaren(r) IM, respectively.
      Consistently, the overall tolerability as judged by the patients and
      investigators was reported as good or excellent in more than 90% of cases in all
      groups. CONCLUSIONS: Overall, the study results indicate that safety and efficacy
      were similar irrespective of the diclofenac formulation used; thus, the new SC
      diclofenac HPbetaCD has an acceptable tolerability profile and may be considered
      a valid alternative to IM-delivered diclofenac formulations.

PMID- 24279689
TI  - Prostanoid receptor EP2 as a therapeutic target.
AB  - Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and
      peripheral) injury models where COX-2 levels correlate with disease progression.
      Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2
      inhibitors, which proved to be effective in reducing the pain and inflammation in
      patients with arthritis and menstrual cramps, but they have not provided any
      benefit to patients with chronic inflammatory neurodegenerative disease.
      Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the
      United States market due to cardiovascular side effects. Thus, future anti
      inflammatory therapy could be targeted through a specific prostanoid receptor
      downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory
      target in a variety of CNS and peripheral diseases. Here we highlight the latest
      developments on the role of EP2 in diseases, mechanism of activation, and small
      molecule discovery targeted either to enhance or to block the function of this
      receptor. 

PMID- 24279692
TI  - Resveratrol attenuates early brain injury after subarachnoid hemorrhage through
      inhibition of NF-kappaB-dependent inflammatory/MMP-9 pathway.

PMID- 24279693
TI  - Cultural consultation as a model for training multidisciplinary mental healthcare
      professionals in cultural competence skills: preliminary results.
AB  - ACCESSIBLE SUMMARY: Lack of cultural competence in care contributes to poor
      experiences and outcomes from care for migrants and racial and ethnic minorities.
      As a result, health and social care organizations currently promote cultural
      competence of their workforce as a means of addressing persistent poor
      experiences and outcomes. At present, there are unsystematic and diverse ways of
      promoting cultural competence, and their impact on clinician skills and patient
      outcomes is unknown. We developed and implemented an innovative model, cultural
      consultation service (CCS), to promote cultural competence of clinicians and
      directly improve on patient experiences and outcomes from care. CCS model is an
      adaptation of the McGill model, which uses ethnographic methodology and medical
      anthropological knowledge. The method and approach not only contributes both to a
      broader conceptual and dynamic understanding of culture, but also to learning of
      cultural competence skills by healthcare professionals. The CCS model
      demonstrates that multidisciplinary workforce can acquire cultural competence
      skills better through the clinical encounter, as this promotes integration of
      learning into day-to-day practice. Results indicate that clinicians developed a
      broader and patient-centred understanding of culture, and gained skills in
      narrative-based assessment method, management of complexity of care, competing
      assumptions and expectations, and clinical cultural formulation. Cultural
      competence is defined as a set of skills, attitudes and practices that enable the
      healthcare professionals to deliver high-quality interventions to patients from
      diverse cultural backgrounds. Improving on the cultural competence skills of the
      workforce has been promoted as a way of reducing ethnic and racial inequalities
      in service outcomes. Currently, diverse models for training in cultural
      competence exist, mostly with no evidence of effect. We established an innovative
      narrative-based cultural consultation service in an inner-city area to work with
      community mental health services to improve on patients' outcomes and clinicians'
      cultural competence skills. We targeted 94 clinicians in four mental health
      service teams in the community. After initial training sessions, we used a
      cultural consultation model to facilitate 'in vivo' learning. During cultural
      consultation, we used an ethnographic interview method to assess patients in the
      presence of referring clinicians. Clinicians' self-reported measure of cultural
      competence using the Tool for Assessing Cultural Competence Training (n = 28, at
      follow-up) and evaluation forms (n = 16) filled at the end of each cultural
      consultation showed improvement in cultural competence skills. We conclude that
      cultural consultation model is an innovative way of training clinicians in
      cultural competence skills through a dynamic interactive process of learning
      within real clinical encounters.

PMID- 24279694
TI  - Consistency in trophic magnification factors of cyclic methyl siloxanes in
      pelagic freshwater food webs leading to brown trout.
AB  - Cyclic volatile methyl siloxanes (cVMS) concentrations were analyzed in the
      pelagic food web of two Norwegian lakes (Mjosa, Randsfjorden), and in brown trout
      (Salmo trutta) and Arctic char (Salvelinus alpinus) collected in a reference lake
      (Femunden), in 2012. Lakes receiving discharge from wastewater treatment plants
      (Mjosa and Randsfjorden) had cVMS concentrations in trout that were up to 2
      orders of magnitude higher than those in Femunden, where most samples were close
      to the limit of quantification (LOQ). Food web biomagnification of cVMS in Mjosa
      and Randsfjorden was quantified by estimation of trophic magnification factors
      (TMFs). TMF for legacy persistent organic pollutants (POPs) were analyzed for
      comparison. Both decamethylcyclopentasiloxane (D5) and
      dodecamethylcyclohexasiloxane (D6) biomagnified with TMFs of 2.9 (2.1-4.0) and
      2.3 (1.8-3.0), respectively. Octamethylcyclotetrasiloxane (D4) was below the LOQ
      in the majority of samples and had substantially lower biomagnification than for
      D5 and D6. The cVMS TMFs did not differ between the lakes, whereas the legacy POP
      TMFs were higher in Mjosa than inRandsfjorden. Whitefish had lower cVMS
      bioaccumulation compared to legacy POPs, and affected the TMF significance for
      cVMS, but not for POPs. TMFs of D5 and legacy contaminants in Lake Mjosa were
      consistent with those previously measured in Mjosa. 

PMID- 24279695
TI  - Case managers for older persons with multi-morbidity and their everyday work - a
      focused ethnography.
AB  - BACKGROUND: Modern-day health systems are complex, making it difficult to assure
      continuity of care for older persons with multi-morbidity. One way of intervening
      in a health system that is leading to fragmented care is by utilising Case
      Management (CM). CM aims to improve co-ordination of healthcare and social
      services. To better understand and advance the development of CM, there is a need
      for additional research that provides rich descriptions of CM in practice. This
      knowledge is important as there could be unknown mechanisms, contextual or
      interpersonal, that contribute to the success or failure of a CM intervention.
      Furthermore, the CM intervention in this study is conducted in the context of the
      Swedish health system, which prior to this intervention was unfamiliar with this
      kind of coordinative service. The aim of this study was to explore the everyday
      work undertaken by case managers within a CM intervention, with a focus on their
      experiences. METHODS: The study design was qualitative and inductive, utilising a
      focused ethnographic approach. Data collection consisted of participant
      observations with field notes as well as a group interview and individual
      interviews with nine case managers, conducted in 2012/2013. The interviews were
      recorded, transcribed verbatim and subjected to thematic analysis. RESULTS: An
      overarching theme emerged from the data: Challenging current professional
      identity, with three sub-themes. The sub-themes were 1) Adjusting to familiar
      work in an unfamiliar role; 2) Striving to improve the health system through a
      new role; 3) Trust is vital to advocacy. CONCLUSIONS: Findings from this study
      shed some light on the complexity of CM for older persons with multi-morbidity,
      as seen from the perspective of case managers. The findings illustrate how their
      everyday work as case managers represents a challenge to their current
      professional identity. These findings could help to understand and promote the
      development of CM models aimed at a population of older persons with complex
      health needs.

PMID- 24279696
TI  - Electrophysiological evidence for the morpheme-based combinatoric processing of
      English compounds.
AB  - The extent to which the processing of compounds (e.g., "catfish") makes recourse
      to morphological-level representations remains a matter of debate. Moreover,
      positing a morpheme-level route to complex word recognition entails not only
      access to morphological constituents, but also combinatoric processes operating
      on the constituent representations; however, the neurophysiological mechanisms
      subserving decomposition, and in particular morpheme combination, have yet to be
      fully elucidated. The current study presents electrophysiological evidence for
      the morpheme-based processing of both lexicalized (e.g., "teacup") and novel
      (e.g., "tombnote") visually presented English compounds; these brain responses
      appear prior to and are dissociable from the eventual overt lexical decision
      response. The electrophysiological results reveal increased negativities for
      conditions with compound structure, including effects shared by lexicalized and
      novel compounds, as well as effects unique to each compound type, which may be
      related to aspects of morpheme combination. These findings support models
      positing across-the-board morphological decomposition, counter to models
      proposing that putatively complex words are primarily or solely processed as
      undecomposed representations, and motivate further electrophysiological research
      toward a more precise characterization of the nature and neurophysiological
      instantiation of complex word recognition. 

PMID- 24279697
TI  - A rare 3q13.31 microdeletion including GAP43 and LSAMP genes.
AB  - BACKGROUND: Interstitial deletions affecting the proximal long arm of chromosome
      3 have been rarely reported in the literature. The deleted segments vary in
      localization and size with different breakpoints making genotype-phenotype
      correlation very difficult. Until now, a girl with a 1.9-Mb interstitial deletion
      of 3q13.2q13.31 and 14 novel patients with deletions in 3q11q23 have been
      reported. RESULTS: Here we report on a 7-year-old girl with neuropsychiatric
      disorders and renal, vascular and skeletal anomalies. Array-CGH analysis revealed
      a small rare inherited 3q13.31 deletion containing only two genes, GAP43 and
      LSAMP. The mutation analysis of the two genes was negative on the other non
      deleted chromosome. GAP43 is considered a crucial component for an effective
      regenerative response in the nervous system and its mRNA is localized exclusively
      to nerve tissue where the protein is linked to the synaptosomal membrane. LSAMP
      is a 64- to 68-kD neuronal surface glycoprotein found in cortical and subcortical
      regions of the limbic system that acts as an adhesion molecule and guides the
      development of specific patterns of neuronal connection. The deleted region is
      adjacent to a "desert gene" region extending 2.099 Mb. CONCLUSIONS: We discuss
      the effects of GAP43 and LSAMP haploinsufficiency, proposing that their deletion
      may be responsible for the main phenotype. Further cases with similar
      microdeletion are expected to be diagnosed and will help to better characterize
      the clinical spectrum of phenotypes associated with 3q13.31 microdeletion.

PMID- 24279698
TI  - Genetic mutations in influenza H3N2 viruses from a 2012 epidemic in Southern
      China.
AB  - BACKGROUND: An influenza H3N2 epidemic occurred throughout Southern China in
      2012. METHODS: We analyzed the hemagglutinin (HA) and neuraminidase (NA) genes of
      influenza H3N2 strains isolated between 2011-2012 from Guangdong. Mutation sites,
      evolutionary selection, antigenic sites, and N-glycosylation within these strains
      were analyzed. RESULTS: The 2011-2012 Guangdong strains contained the HA-A214S,
      HA-V239I, HA-N328S, NA-L81P, and NA-D93G mutations, similar to those seen in the
      A/ Perth/16/2009 influenza strain. The HA-NSS061-063 and NNS160-162 glycosylation
      sites were prevalent among the 2011-2012 Guangdong strains but the NA-NRS402-404
      site was deleted. Antigenically, there was a four-fold difference between
      A/Perth/16/2009 -like strains and the 2011-2012 Guangdong strains. CONCLUSION:
      Antigenic drift of the H3N2 subtype contributed to the occurrence of the Southern
      China influenza epidemic of 2012.

PMID- 24279699
TI  - Immunohistochemical expression of the mammalian target of rapamycin pathway in
      penile squamous cell carcinomas: a tissue microarray study of 112 cases.
AB  - AIMS: The aim of this study was to evaluate the immunohistochemical expression of
      mammalian target of rapamycin (mTOR) pathway-related biomarkers in penile
      carcinomas, and to assess associations with histological type, histological
      grade, and human papillomavirus (HPV) infection. METHODS AND RESULTS: We built
      four tissue microarrays from 112 invasive penile squamous cell carcinomas, and
      evaluated the immunohistochemical expression of PTEN, phospho-AKT, phospho-mTOR,
      and phospho-S6. We found decreased or loss of PTEN expression in 87% of cases.
      Warty and/or basaloid carcinomas had a higher proportion of PTEN loss (P = 0.02),
      whereas keratinizing tumours showed higher levels of phospho-S6 (P = 0.009);
      phospho-AKT and phospho-mTOR levels were not significantly different between
      warty/basaloid and keratinizing carcinomas (P = 0.75 and P = 0.77, respectively).
      PTEN was not associated with histological grade (P = 0.18). Expression levels of
      phospho-S6 were significantly higher in low-grade tumours (P = 0.001), whereas
      expression levels of phospho-AKT and phospho-mTOR were slightly higher in high
      grade tumours (P = 0.01 and P = 0.35, respectively). We did not find any
      association between HPV infection and mTOR markers (P >= 0.2 in all cases).
      CONCLUSIONS: Our results provide evidence of dysregulation of the mTOR pathway in
      penile carcinomas independently of HPV infection. Future clinical studies should
      further evaluate the prognostic and predictive usefulness of these markers in
      patients with penile cancer.

PMID- 24279700
TI  - Role of N-terminal residues on folding and stability of C-phycoerythrin:
      simulation and urea-induced denaturation studies.
AB  - The conformational state of biliproteins can be determined by optical properties
      of the covalently linked chromophores. Recently determined crystal structure of
      truncated form of alpha-subunit of cyanobacterial phycoerythrin (alphaC-PE) from
      Phormidium tenue provides a new insight into the structure-function relationship
      of alphaC-PE. To compare their stabilities, we have measured urea-induced
      denaturation transitions of the full length alphaC-PE (FL-alphaC-PE) and
      truncated alphaC-PE (Tr-alphaC-PE) followed by observing changes in absorbance at
      565 nm, fluorescence at 350 and 573 nm, and circular dichroism at 222 nm as a
      function of [urea], the molar concentration of urea. The transition curve of each
      protein was analyzed for DeltaG(D)(0), the value of Gibbs free energy change on
      denaturation (DeltaG(D)) in the absence of urea; m, the slope (=??G(D)/?[urea]),
      and C(m), the midpoint of the denaturation curve, i.e. [urea] at which DeltaG(D)
      = 0. A difference of about 10% in DeltaG(D)(0) observed between FL-alphaC-PE and
      Tr-alphaC-PE, suggests that the two proteins are almost equally stable, and the
      natural deletion of 31 residues from the N-terminal side of the full length
      protein does not alter its stability. Furthermore, normalization of probes shows
      that the urea-induced denaturation of both the proteins is a two-state process.
      Folding of both structural variants (Tr-alphaC-PE and FL-alphaC-PE) of P. tenue
      were also studied using molecular dynamics simulations at 300 K. The results show
      clearly that the stability of the proteins is evenly distributed over the whole
      structure indicating no significant role of N-terminal residues in the stability
      of both proteins.

PMID- 24279701
TI  - A comparison of microbiology and demographics among patients with healthcare
      associated, hospital-acquired, and ventilator-associated pneumonia: a
      retrospective analysis of 1184 patients from a large, international study.
AB  - BACKGROUND: Acceptance of healthcare-associated pneumonia (HCAP) as an entity and
      the associated risk of infection by potentially multidrug-resistant (MDR)
      organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas
      and Acinetobacter have been debated. We therefore compared patients with HCAP,
      hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP)
      enrolled in a trial comparing linezolid with vancomycin for treatment of
      pneumonia. METHODS: The analysis included all patients who received study drug.
      HCAP was defined as pneumonia occurring < 48 hours into hospitalization and
      acquired in a long-term care, subacute, or intermediate health care facility;
      following recent hospitalization; or after chronic dialysis. RESULTS: Data from
      1184 patients (HCAP = 199, HAP = 379, VAP = 606) were analyzed. Compared with HAP
      and VAP patients, those with HCAP were older, had slightly higher severity
      scores, and were more likely to have comorbidities. Pseudomonas aeruginosa was
      the most common gram-negative organism isolated in all pneumonia classes [HCAP,
      22/199 (11.1%); HAP, 28/379 (7.4%); VAP, 57/606 (9.4%); p = 0.311]. Acinetobacter
      spp. were also found with similar frequencies across pneumonia groups. To address
      potential enrollment bias toward patients with MRSA pneumonia, we grouped
      patients by presence or absence of MRSA and found little difference in
      frequencies of Pseudomonas and Acinetobacter. CONCLUSIONS: In this population of
      pneumonia patients, the frequencies of MDR gram-negative pathogens were similar
      among patients with HCAP, HAP, or VAP. Our data support inclusion of HCAP within
      nosocomial pneumonia guidelines and the recommendation that empiric antibiotic
      regimens for HCAP should be similar to those for HAP and VAP.

PMID- 24279702
TI  - Potassium nutrition of ectomycorrhizal Pinus pinaster: overexpression of the
      Hebeloma cylindrosporum HcTrk1 transporter affects the translocation of both K(+)
      and phosphorus in the host plant.
AB  - Mycorrhizal associations are known to improve the hydro-mineral nutrition of
      their host plants. However, the importance of mycorrhizal symbiosis for plant
      potassium nutrition has so far been poorly studied. We therefore investigated the
      impact of the ectomycorrhizal fungus Hebeloma cylindrosporum on the potassium
      nutrition of Pinus pinaster and examined the involvement of the fungal potassium
      transporter HcTrk1. HcTrk1 transcripts and proteins were localized in
      ectomycorrhizas using in situ hybridization and EGFP translational fusion
      constructs. Importantly, an overexpression strategy was performed on a H.
      cylindrosporum endogenous gene in order to dissect the role of this transporter.
      The potassium nutrition of mycorrhizal pine plants was significantly improved
      under potassium-limiting conditions. Fungal strains overexpressing HcTrk1 reduced
      the translocation of potassium and phosphorus from the roots to the shoots of
      inoculated plants in mycorrhizal experiments. Furthermore, expression of HcTrk1
      and the phosphate transporter HcPT1.1 were reciprocally linked to the external
      inorganic phosphate and potassium availability. The development of these
      approaches provides a deeper insight into the role of ectomycorrhizal symbiosis
      on host plant K(+) nutrition and in particular, the K(+) transporter HcTrk1. The
      work augments our knowledge of the link between potassium and phosphorus
      nutrition via the mycorrhizal pathway. 

PMID- 24279703
TI  - The regulation of gastric acid secretion - clinical perspectives.
AB  - The purpose of this review, based upon 40 years of research, is to clear old
      controversies. The gastric juice is a strong acid with active enzymes (pepsin and
      lipase); ideal for killing swallowed microorganisms. Totally isolated rat stomach
      and histamine determination. Human gastric carcinomas were examined for ECL cell
      differentiation because tumours found in rodents after dosing with inhibitors of
      acid secretion were reclassified to be of ECL cell origin. The gastrin receptor
      is localized to the ECL cell only, where gastrin stimulates the function and
      growth. Drug-induced hypo-acidity induces hypergastrinaemia and ECL cell
      hyperplasia responsible for rebound acid hypersecretion. Every condition with
      long-term hypergastrinaemia disposes to ECL cell neoplasia. In man, both atrophic
      gastritis and gastrinoma lead to ECL cell carcinoids. Proton pump inhibitors
      induce hypergastrinaemia with ECL cell hyperplasia and ECL cell carcinoids that
      disappear when stopping treatment. The gastrin antagonist netazepide induces
      regression of ECL cell carcinoids due to atrophic gastritis. Human gastric
      carcinomas of diffuse type, particularly the signet-ring subtype, show ECL cell
      differentiation, suggesting involvement of gastrin in the carcinogenesis.
      Helicobacter pylori (Hp) causes gastritis and peptic ulcer, and when infecting
      the antrum only gives a slight hypergastrinaemia with acid hypersecretion
      predisposing to duodenal ulcer, but protecting from gastric cancer. When Hp
      infection spreads to oxyntic mucosa, it induces atrophy, reduced acid secretion
      and marked hypergastrinaemia and cancer.It is remarkable that the interaction
      between Hp and gastrin may explain the pathogenesis of most diseases in the upper
      gastrointestinal tract. 

PMID- 24279704
TI  - Size dependence of the dispersion relation for the interface state between
      NaCl(100) and Ag(111).
AB  - This study investigates the interface state electron dispersion relation between
      NaCl(100) islands and Ag(111) dependent upon NaCl island size. Both onset energy
      and effective mass are size dependent. However, these dependencies are relevant
      at different island sizes. We trace back this effective mass dependency to a
      misfit-induced strain based on atomically resolved images. Our results open up
      new avenues for the development of nanodevices by tuning the effective electron
      mass via strain of the insulating component. 

PMID- 24279706
TI  - Bariatric surgery modulates circulating and cardiac metabolites.
AB  - Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation offer
      profound metabolic enhancement in addition to their well-recognized weight loss
      effects. They are associated with significant reduction in cardiovascular disease
      risk and mortality, which suggests a surgical modification on cardiac metabolism.
      Metabolic phenotyping of the cardiac tissue and plasma postsurgery may give
      insight into cardioprotective mechanisms. The aim of the study was to compare the
      metabolic profiles of plasma and heart tissue extracts from RYGB- and sham
      operated Wistar rats to identify the systemic and cardiac signature of metabolic
      surgery. A total of 27 male Wistar rats were housed individually for a week and
      subsequently underwent RYGB (n = 13) or sham (n = 14) operation. At week 8
      postoperation, a total of 27 plasma samples and 16 heart tissue samples (8 RYGB;
      8 Sham) were collected from animals and analyzed using (1)H nuclear magnetic
      resonance (NMR) spectroscopy and ultra performance liquid chromatography (UPLC
      MS) to characterize the global metabolite perturbation induced by RYGB operation.
      Plasma bile acids, phosphocholines, amino acids, energy-related metabolites,
      nucleosides and amine metabolites, and cardiac glycogen and amino acids were
      found to be altered in the RYGB operated group. Correlation networks were used to
      identify metabolite association. The metabolic phenotype of this bariatric
      surgical model inferred systematic change in both myocardial and systemic
      activity post surgery. The altered metabolic profile following bariatric surgery
      reflects an enhancement of cardiac energy metabolism through TCA cycle
      intermediates, cardiorenal protective activity, and biochemical caloric
      restriction. These surgically induced metabolic shifts identify some of the
      potential mechanisms that contribute toward bariatric cardioprotection through
      gut microbiota ecological fluxes and an enterocardiac axis to shield against
      metabolic syndrome of cardiac dysfunction. 

PMID- 24279707
TI  - Progression of pulse pressure in kidney recipients durably exposed to CsA is a
      risk factor for epithelial phenotypic changes: an ancillary study of the CONCEPT
      trial.
AB  - In this ancillary study of the CONCEPT trial, we studied the role of CsA
      withdrawal at 3 months (3M) post-transplant on the intensity of epithelial
      phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12 M
      surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was
      reported to have improved mean graft function at 12 M, it did not reduce the
      score of EPC (1.73 +/- 1.15 in the SRL group vs. 1.87 +/- 1 in the CsA group, P =
      0.61). Acute rejection, which had occurred twice more frequently in SRL-converted
      patients included here, was associated with 12 M EPC. Interestingly, we observed
      that the patients durably exposed to CsA and who developed 12 M EPC had a
      significant progression of blood pulse pressure (pp) from 1 to 6M post
      transplantation (Deltapp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9
      M and pp progression from 1 to 6M were significantly associated with the
      development of EPC at 12 M in renal grafts. Logistic regression analysis revealed
      that a high 6M pp (>= 60 mmHg) was an independent risk factor for 12 M EPC with
      an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14-4.4, P = 0.02) after
      adjustment with recipient's and donor's age, acute rejection incidence and
      immunosuppressive regimen. A post hoc analysis of the data collected in the whole
      population CONCEPT study revealed that pp was significantly higher at 6 months in
      patients maintained on CsA and that at this time point pp correlated negatively
      with GFR at 1 year.

PMID- 24279708
TI  - Clinical outcomes of cataract surgery in very elderly adults.
AB  - OBJECTIVES: To investigate the clinical outcomes of cataract surgery elderly
      adults. DESIGN: Retrospective cohort study. SETTING: Two clustered hospitals.
      PARTICIPANTS: Two hundred seven individuals aged 90 and older who underwent
      cataract surgery for primary senile cataracts. MEASUREMENTS: Best-corrected
      preoperative and postoperative Snellen visual acuity, type of cataract, surgical
      techniques, preoperative systemic or ocular comorbidities, and intraoperative and
      postoperative complications were assessed. Improvement of visual acuity was
      defined as a decrease in logMAR acuity of 0.1. Factors associated with visual
      outcome within 6 months after surgery were identified using logistic regression
      modeling. The duration of postoperative survival was calculated. RESULTS: In the
      207 participants (mean age 92.0 +/- 2.1), 79.7% achieved visual improvement after
      cataract surgery. Forty-eight percent (mean age 97.4 +/- 2.8) were alive on
      December 31, 2012. The most common systemic comorbidities were hypertension
      (66.2%), diabetes mellitus (25.1%), and myocardial infarction (19.8%). Age
      related macular degeneration (AMRD) (15.9%), glaucoma (10.6%), and myopic
      degeneration (5.3%) were the three most common ocular comorbidities.
      Uncomplicated cataract surgery was performed in 87.0% cases. The most common
      complications were vitreous loss (8.2%), posterior capsular rupture (7.2%), and
      zonular rupture (4.8%). Participants with AMRD (P = .001, odds ratio (OR) = 4.77,
      95% confidence interval (CI) = 1.86-12.26) and vitreous loss (P = .001, OR =
      12.86, 95% CI = 2.71-61.10) were less likely to achieve postoperative visual
      improvement. CONCLUSION: Despite a high prevalence of systemic and ocular
      comorbidities in very elderly adults, good clinical outcomes of cataract surgery
      were attainable. ARMD and vitreous loss were associated with a lower chance of
      postoperative visual improvement.

PMID- 24279709
TI  - Hyper-connectivity of subcortical resting-state networks in social anxiety
      disorder.
AB  - Social anxiety disorder-related alterations in basal ganglia regions, such as
      striatum and globus pallidus, though evident from metabolic imaging, remain to be
      explored using seed-based resting-state functional connectivity magnetic
      resonance imaging. Capitalizing on the enhanced sensitivity of a multichannel
      array coil, we collected high-resolution (2-mm isotropic) data from medication
      naive patients and healthy control participants. Subcortical resting-state
      networks from structures including the striatum (caudate and putamen), globus
      pallidus, thalamus, amygdala, and periaqueductal gray were compared between the
      two groups. When compared with controls, the caudate seed revealed significantly
      higher functional connectivity (hyper-connectivity) in the patient group in
      medial frontal, prefrontal (anterior and dorsolateral), orbito-frontal, and
      anterior cingulate cortices, which are regions that are typically associated with
      emotional processing. In addition, with the putamen seed, the patient data
      exhibited increased connectivity in the fronto-parietal regions (executive
      control network) and subgenual cingulate (affective network). The globus pallidus
      seed showed significant increases in connectivity in the patient group, primarily
      in the precuneus, which is part of the default mode network. Significant hyper
      connectivity in the precuneus, interior temporal, and parahippocampal cortices
      was also observed with the thalamus seed in the patient population, when compared
      with controls. With amygdala as seed region, between-group differences were
      primarily in supplementary motor area, inferior temporal gyrus, secondary visual
      cortex, angular gyrus, and cingulate gyrus. Seed from periaqueductal gray
      resulted in hyper-connectivity in the patient group, when compared with controls,
      in dorsolateral prefrontal cortex, precuneus, middle temporal gyrus, and inferior
      parietal lobule. In all the subcortical regions examined in this study, the
      control group did not have any significant enhancements in functional
      connectivity when compared with the patient group.

PMID- 24279710
TI  - Paediatric intensive care nurses' and doctors' perceptions on nurse-led protocol
      directed ventilation weaning and extubation.
AB  - BACKGROUND: Nurse-led (protocol-directed) ventilation weaning (NLVW) is utilized
      in adult intensive care and has shown to be safe and reduce ventilation times.
      Our paediatric intensive care unit (PICU) implemented a NLVW (and extubation)
      protocol in 2004, yet it was observed that some NLVW-trained nurses were not
      undertaking the role in practice. AIMS: To explore PICU nurses' and doctors'
      perceptions of and barriers to NLVW on a UK PICU, with the aim of facilitating
      more NLVW on our PICU by reducing these barriers. METHODS: A cross-sectional
      electronic survey was used to collect data from both nurse ventilation weaners
      and all medical staff and advanced nurse practitioners (ANPs) on one PICU.
      RESULTS: Our survey response rates were 90% (36/40) nursing and 54% (20/37)
      medical. The four top reasons cited for nurses not being able to wean by protocol
      were not being allocated to a 'weanable' patient, being in an in-charge or runner
      role, high clinical workload and a perceived lack of support from medical
      staff/ANPs. The restrictive nature of our protocol also emerged as a key issue by
      all staff. The medical survey revealed an overwhelming positive response to NLVW
      with 90% believing that experienced PICU nurses should be allowed to wean
      ventilation. In contrast to the nurses perceived lack of support or encouragement
      for NLVW, medical staff rated their encouragement for the nurses to undertake
      this role as high. CONCLUSIONS: NLVW is a complex process, and factors that
      impair or facilitate this process relate not only to the weaning protocol itself,
      but also organizational processes and structural factors in a PICU. RELEVANCE TO
      CLINICAL PRACTICE: This paper highlights the complexities involved in instituting
      and establishing a nurse-led, protocol-driven ventilation weaning process within
      a PICU. Further, in depth research is required to examine both PICU nurses and
      doctors attitudes to NLVW both in the UK and across Europe.

PMID- 24279711
TI  - Compartmental genomics in living cells revealed by single-cell nanobiopsy.
AB  - The ability to study the molecular biology of living single cells in
      heterogeneous cell populations is essential for next generation analysis of
      cellular circuitry and function. Here, we developed a single-cell nanobiopsy
      platform based on scanning ion conductance microscopy (SICM) for continuous
      sampling of intracellular content from individual cells. The nanobiopsy platform
      uses electrowetting within a nanopipette to extract cellular material from living
      cells with minimal disruption of the cellular milieu. We demonstrate the
      subcellular resolution of the nanobiopsy platform by isolating small
      subpopulations of mitochondria from single living cells, and quantify mutant
      mitochondrial genomes in those single cells with high throughput sequencing
      technology. These findings may provide the foundation for dynamic subcellular
      genomic analysis. 

PMID- 24279712
TI  - Cost-effective and efficient apparatus for electroelution of micro- and macrogram
      quantities of proteins from polyacrylamide gels.
AB  - Protein recovery from gel electrophoresis plays a significant role in functional
      genomics and proteomics. To assist in this, a simple, cost-effective, and
      efficient apparatus for electroelution of proteins has been designed. The
      performance of the apparatus was demonstrated using the proteins bovine serum
      albumin (BSA), phosphorylase, ovalbumin, pepsin, and trypsinogen. In all the
      cases the yield of elution was found to be consistently greater than 85% and the
      proteins could be eluted without degradation in less than 15 min. The utility of
      this method can be extended to protein elution from denatured and native
      polyacrylamide gels, DNA purification from agarose gels, and oligomeric primers
      purification from polyacrylamide gels. In addition to this, the method offers an
      effortless purification and characterization of microbial extracellular proteins.
      The eluted proteins can be directly used in N-terminal amino acid sequencing, and
      in amino acid and proteomics analyses.

PMID- 24279713
TI  - Electronic opioid risk assessment program for chronic pain patients: barriers and
      benefits of implementation.
AB  - OBJECTIVES: A preliminary electronic pain assessment program known as Pain
      Assessment Interview Network, Clinical Advisory System (painCAS), was implemented
      in 2 pain centers over the course of 10 months to understand the tool's impact on
      opioid risk assessment documentation and clinical workflow. The program contains
      validated electronic versions of screeners for opioid misuse risk (SOAPP-R and
      Current Opioid Misuse Measure). METHODS: Charts of patients with an initial and 2
      follow-up visits were randomly selected for review of presence of opioid risk
      assessments before and after implementation of the electronic assessment program.
      Clinical and administrative staff members were interviewed to gain their
      perceptions of the impact of the program. RESULTS: Significant increases were
      observed in the documentation of opioid risk assessments between the baseline
      patient chart reviews before implementation of the program (n = 66) and the
      postintervention patient chart reviews after the implementation of the program (n
      = 39), for both initial and follow-up clinic visits (P < 0.001). Specific
      benefits of the program identified by 7 clinicians and 8 administrators included
      ease of use, reduced paperwork, completion of the assessment before the clinic
      visit, and incorporation of information directly into an electronic medical
      record (EMR). Perceived barriers to implementation included poor patient
      compliance, changes in administration workflow, and difficulties associated with
      patients with no email addresses, and limited computer skills. CONCLUSIONS:
      Implementation of an opioid risk electronic pain assessment program significantly
      increased the likelihood that a risk assessment would be included in the medical
      record, which has implications for improvement of quality of care.

PMID- 24279714
TI  - Enhanced saccharification of rice straw by overexpression of rice exo-glucanase.
AB  - BACKGROUND: Efficient production of carbon-neutral biofuels is key to resolving
      global warming and exhaustion of fossil fuels. Cellulose, which is the most
      abundant biomass, is physically strong and biochemically stable, and these
      characteristics lead to difficulty of efficient saccharification of cellulosic
      compounds for production of fermentable glucose and other sugars. RESULTS: We
      transformed rice with overexpressing constructs of rice genes encoding each of
      three classes of cellulases. The exo-glucanase overexpressing plants showed
      various abnormalities in leaf such as division of leaf blade, crack on leaf
      surface, excess lacunae in midrib structure and necrotic colour change. The
      overexpressing plants also showed sterility. Noticeably, these plants showed
      enhanced saccharification of stems after maturation. These results indicate that
      overexpression of the exo-glucanase gene brought about various developmental
      defects associated with modification of cell wall and enhanced saccharification
      in rice. On the other hand, endo-glucanase-overexpressing plants could not be
      obtained, and overexpression of beta-glucosidase brought about no effect on plant
      growth and development. CONCLUSIONS: Our results indicate that genetic
      engineering of cellulosic biomass plants by overexpressing cellulase genes will
      be one of the approaches to confer enhanced saccharification ability for
      efficient production of cellulosic biofuels such as ethanol.

PMID- 24279715
TI  - Depressive symptoms and pain complaints as predictors of later development of
      depression in Portuguese middle-aged women.
AB  - Pain complaints and depressive symptoms seem to be risk factors for future
      depressive episodes. We present a one-year follow-up study on Portuguese women
      and primary health care (initial sample: n = 503). We used the Center for
      Epidemiologic Studies Depression Scale (CES-D), a short questionnaire on pain,
      and clinical interviews. We used forward stepwise logistic regression analysis to
      define models that enable the prediction of developing a major depressive episode
      in the one-year follow-up. We concluded that nondepressed women with (a) high
      scores (>=28) at the CES-D, (b) a high severity of pain index, and (c) fatigue
      complaints at the baseline were particularly at risk. 

PMID- 24279716
TI  - Heat shock protein 70 reduces alpha-synuclein-induced predegenerative neuronal
      dystrophy in the alpha-synuclein viral gene transfer rat model of Parkinson's
      disease.
AB  - AIMS: It has become increasingly evident that the nigrostriatal degeneration
      associated with Parkinson's disease initiates at the level of the axonal
      terminals in the putamen, and this nigrostriatal terminal dystrophy is either
      caused or exacerbated by the presence of alpha-synuclein immunopositive neuronal
      inclusions. Therefore, strategies aimed at reducing alpha-synuclein-induced early
      neuronal dystrophy may slow or halt the progression to overt nigrostriatal
      neurodegeneration. Thus, this study sought to determine if adeno-associated virus
      (AAV) mediated overexpression of two molecular chaperone heat shock proteins,
      namely Hsp27 or Hsp70, in the AAV-alpha-synuclein viral gene transfer rat model
      of Parkinson's disease could prevent alpha-synuclein-induced early neuronal
      pathology. METHODS: Male Sprague-Dawley rats were intranigrally coinjected with
      pathogenic (AAV-alpha-synuclein) and putative therapeutic (AAV-Hsp27 or AAV
      Hsp70) viral vectors and were sacrificed 18 weeks postviral injection. RESULTS:
      Intranigral injection of AAV-alpha-synuclein resulted in significant alpha
      synuclein accumulation in the substantia nigra and striatal terminals which led
      to significant dystrophy of nigrostriatal dopaminergic neurons without overt
      nigrostriatal neurodegeneration. Coinjection of AAV-Hsp70, but not AAV-Hsp27,
      significantly reduced AAV-alpha-synuclein-induced neuronal dystrophy.
      CONCLUSIONS: These data confirm that overexpression of Hsp70 holds significant
      potential as a disease-modulating therapeutic approach for Parkinson's disease,
      with protective effects against early-onset alpha-synuclein-induced pathology
      demonstrated in the AAV-alpha-synuclein model.

PMID- 24279717
TI  - Early activation of Broca's area in grammar processing as revealed by the
      syntactic mismatch negativity and distributed source analysis.
AB  - Though activation of Broca's region in the combinatorial processing of symbols
      (language, music) has been revealed by neurometabolic studies, most previous
      neurophysiological research found the earliest grammar indices in the temporal
      cortex, with inferior-frontal generators becoming active at relatively late
      stages. We use the attention- and task-free syntactic mismatch negativity (sMMN)
      event-related potential (ERP) to measure rapid and automatic sensitivity of the
      human brain to grammatical information in participants' native language (French).
      Further, sources underlying the MMN were estimated by applying the Parametrical
      Empirical Bayesian (PEB) approach, with the Multiple Sparse Priors (MSP)
      technique. Results showed reliable grammar-related activation focused on Broca's
      region already in the 150-190 ms time window, providing robust documentation of
      its involvement in the first stages of syntactic processing.

PMID- 24279718
TI  - Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki
      ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic
      lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to
      crizotinib: a case report.
AB  - BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma
      patients are generally highly responsive to the dual anaplastic lymphoma kinase
      and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire
      resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors
      from having a prolonged beneficial effect. The molecular mechanisms responsible
      for crizotinib resistance are beginning to emerge, e.g., in some anaplastic
      lymphoma kinase-positive non-small cell lung carcinomas the development of
      secondary mutations in this gene has been described. However, the events behind
      crizotinib-resistance currently remain largely uncharacterized. Thus, we report
      on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient
      with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2
      Kirsten rat sarcoma viral oncogene homolog mutations upon development of
      crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking
      male was diagnosed with anaplastic lymphoma kinase -positive pulmonary
      adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in
      complete objective response in the thorax and partial response in the abdomen,
      but after 8 months of therapy the patient acquired resistance and progressed.
      Biopsies from new metastases revealed development of epidermal growth factor
      receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations
      concomitant with the original anaplastic lymphoma kinase gene rearrangement and
      without signs of anaplastic lymphoma kinase fusion gene amplification or
      secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge,
      this is the first report of an anaplastic lymphoma kinase-positive pulmonary
      adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new
      somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten
      rat sarcoma viral oncogene homolog genes, respectively, concomitant with the
      original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver
      mutations, usually considered mutually exclusive, may coexist in advanced non
      small cell lung carcinoma that becomes resistant to crizotinib, presumably
      because heterogeneous tumor clones utilize epidermal growth factor receptor
      and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to
      circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by
      crizotinib. The identification of new targetable somatic mutations by tumor re
      biopsy may help clarify the mechanism behind the development of the acquired
      crizotinib resistance and pave the way for combined strategies involving multiple
      targeted therapies.

PMID- 24279719
TI  - Detection of hepatitis C virus (HCV) negative strand RNA and NS3 protein in
      peripheral blood mononuclear cells (PBMC): CD3+, CD14+ and CD19+.
AB  - BACKGROUND: Although hepatitis C virus (HCV) is primarily hepatotropic, markers
      of HCV replication were detected in peripheral blood mononuclear cells (PBMC) as
      well as in ex vivo collected tissues and organs. Specific strains of HCV were
      found to be capable to infect cells of the immune system: T and B cells and
      monocytes/macrophages as well as cell lines in vitro. The direct invasion of
      cells of the immune system by the virus may be responsible for extrahepatic
      consequences of HCV infection: cryoglobulinemia and non-Hodgkin's lymphoma.The
      aim of the present study was to determine the prevalence of markers of HCV
      infection: negative strand HCV RNA and non-structural NS3 protein in PBMC
      subpopulations: CD3+, CD14+ and CD19+. The presence of virus and the proportion
      of affected cells within a particular PBMC fraction could indicate a principal
      target cell susceptible for HCV. METHODS: PBMC samples were collected from 26
      treatment-free patients chronically infected with HCV. PBMC subpopulations: CD3+,
      CD14+, CD19+ were obtained using positive magnetic separation. The presence of
      negative strand RNA HCV and viral NS3 protein were analyzed by strand-specific RT
      PCR and NS3 immunocytochemistry staining. RESULTS: Negative strand HCV RNA was
      detectable in 7/26 (27%), whereas NS3 protein in 15/26 (57.6%) of PBMC samples.
      At least one replication marker was found in 13/26 (50%) of CD3+ cells then in
      8/26 (30.8%) of CD14+ and CD19+ cells. The highest percentage of cells harboring
      viral markers in single specimen was also observed in CD3+ (2.4%), then in CD19+
      (1.2%), and much lower in CD14+ (0.4%) cells. CONCLUSIONS: Our results indicate
      that CD3+ cells are a dominant site for extrahepatic HCV replication, although
      other PBMC subpopulations may also support virus replication.

PMID- 24279720
TI  - Malaria case management in Papua New Guinea following the introduction of a
      revised treatment protocol.
AB  - BACKGROUND: This paper reports on the availability of diagnostic tools and
      recommended anti-malarials in the 12-month period immediately following the
      implementation of a new national malaria treatment protocol (NMTP) in Papua New
      Guinea (PNG). Health worker adherence to the new NMTP is also examined and
      comparisons made with previously reported pre-implementation findings. METHODS: A
      countrywide cross-sectional survey in randomly selected primary health care
      facilities (n = 88). Data were collected via passive observation of the clinical
      case management of fever or suspected malaria patients and via an interviewer
      administered questionnaire completed with the officer in charge of each
      participating health care facility. RESULTS: Malaria rapid diagnostic tests
      (RDTs) and the new first-line anti-malarial medication, artemether-lumefantrine
      (AL), were available in 53.4% and 51.1% of surveyed heath facilities,
      respectively. However, they were more widely available in the larger health
      centres as compared to the smaller aid-posts (90.2% vs. 21.3% and 87.8% vs.
      19.2%, respectively). Overall, 68.3% of observed fever cases (n = 445) were
      tested for malaria by RDT and 39% prescribed an anti-malarial, inclusive of 98.2%
      of RDT positive patients and 19.8% of RDT negative cases. The availability and
      use of malaria RDTs was greater in the current survey as compared to pre
      implementation of the new NMTP (8.9% vs. 53.4% & 16.2% vs. 68.3%, respectively)
      as was the availability of AL (0% vs. 51.1%). The percentage of fever patients
      prescribed anti-malarials decreased substantially post implementation of the new
      NMTP (96.4% vs. 39.0%). CONCLUSIONS: PNG has achieved high coverage of malaria
      RDTs and AL at the health centre level, but these resources have yet to reach the
      majority of aid-posts. Malaria case management practice has substantially changed
      in the 12-month period immediately following the new NMTP, although full protocol
      adherence was rarely observed.

PMID- 24279721
TI  - Autonomy-supportive intervention: an evolutionary concept analysis.
AB  - AIM: This paper is a report of an analysis of the concept of an autonomy
      supportive intervention. BACKGROUND: A large proportion of chronic illnesses can
      be prevented by positive health behaviour changes. The aim of an autonomy
      supportive intervention is to increase perceived autonomy support, which, in
      turn, increases positive health behaviour changes. Its known core components are
      choice, rationale and empathy. Identifying and analysing the antecedents,
      attributes and consequences of an autonomy-supportive intervention will increase
      the clarity of this concept. DESIGN: Concept analysis. DATA SOURCES: Sources were
      63 papers describing an autonomy-supportive intervention in health behaviour
      changes indexed in CINAHL, PsycINFO and MEDLINE (all dates until July 2012).
      METHODS: Rodgers' evolutionary method of concept analysis was used to help
      identify and analyse the antecedents, attributes and consequences of the concept.
      RESULTS: More evolution was found in the disciplines of nursing and psychology
      compared with medicine in relation to the use of an autonomy-supportive
      intervention in theoretical frameworks. The antecedents included assessment prior
      to intervention delivery, intervention providers' beliefs, and skills training. A
      lack of homogeneity in the manner in which the attributes were described was
      found in the literature across disciplines and the attributes were classified
      under five components instead of three: choice, rationale, empathy, collaboration
      and strengths. CONCLUSION: An autonomy-supportive intervention is a useful
      concept across healthcare disciplines and future research should aim at
      identifying which attributes and components of an autonomy-supportive
      intervention may be more effective in increasing perceived autonomy support.

PMID- 24279722
TI  - Still scratching the surface: how much of the 'black box' of soil ectomycorrhizal
      communities remains in the dark?

PMID- 24279723
TI  - The effect of rehabilitation on health-care utilisation in COPD patients in
      Copenhagen.
AB  - INTRODUCTION: The Integrated Rehabilitation Programme for Chronic Conditions
      project (SIKS) implemented rehabilitation programmes for people with four chronic
      conditions in the local area within the Municipality of Copenhagen. OBJECTIVES:
      The objective of this study was to evaluate the impact of rehabilitation on
      health-care utilisation in chronic obstructive pulmonary disease (COPD) patients
      as a subgroup of SIKS. METHODS: For the analyses, data from Danish National
      Registers' were obtained. The following outcomes were analysed: (i) COPD hospital
      admissions, (ii) COPD bed days, (iii) COPD outpatient visits, (iv) COPD emergency
      room visits, (v) general practitioner visits, (vi) specialist visits, and (vii)
      COPD specific medication. The rehabilitation group consisted of 118 patients who
      completed the programme. The control group consisted of 236 COPD patients in
      Copenhagen who did not undergo rehabilitation and were matched with the
      intervention group according to propensity score calculated on the basis of
      patient socio-demographic characteristics and health-care utilisation pattern in
      2 years prior to the rehabilitation programme. The effect was assessed by
      applying the principle of difference-in-difference analysis. RESULTS: Compared
      with their matched controls, the patients participating in the rehabilitation
      programme showed a statistically significantly smaller increase in hospital
      admissions, bed days and outpatient visits. CONCLUSIONS: The study provides the
      policy decision makers in the Municipality of Copenhagen with an assessment of
      the effect of a real-life intervention. It shows that the pulmonary
      rehabilitation programme introduced had the anticipated effects on health-care
      utilisation. The study also suggests that the methods used for evaluation were
      appropriate.

PMID- 24279724
TI  - National trends in advanced outpatient diagnostic imaging utilization: an
      analysis of the medical expenditure panel survey, 2000-2009.
AB  - BACKGROUND: Concerns have been raised regarding growth in advanced diagnostic
      imaging use. This study evaluated trends in national outpatient MRI/CT
      utilization rates during 2000-2009 and factors associated with utilization.
      METHODS: This retrospective database analysis used data on all respondents in the
      nationally representative U.S. Medical Expenditure Panel Survey (MEPS) during
      2000-2009. Visits involving advanced diagnostic imaging were identified based on
      self-reported use of MRI or CT tests at emergency departments, office-based
      medical providers, and outpatient departments. The imaging utilization rate was
      defined as the number of outpatient visits with MRI/CT per 1,000 person-years.
      Results were weighted to create nationally representative estimates at the person
      year level for each year and the pooled 10-year period. A multivariate logistic
      regression was estimated to identify predictors of imaging use. RESULTS: A total
      of 319,246 person-years were included in the analysis. MRI/CT utilization rates
      increased from 64.3 to 109.1 per 1,000 person years from 2000 to 2009, with older
      persons, females and Medicare enrollees having higher rates of use. Growth in
      imaging slowed in recent years; the average annual decline in the imaging growth
      rate was larger than that for all outpatient services (4.7% vs. 0.9%). The
      percentage of respondents with MRI/CT use (6.7% during 2000-2009) also increased
      at a slower rate in later years and declined during 2007-2009. The average number
      of MRI/CT visits among imaging users was steady at about 1.5 visits during 2000
      2009. Age, female gender, White race, HMO participation, and all payer types (vs.
      uninsured) were significant predictors of imaging use. Compared to 2005, years
      2000-2003 were associated with a significantly lower likelihood of imaging use,
      while years 2004-2009 were not significantly associated, suggesting a slow-down
      in later years. CONCLUSIONS: Growth in advanced imaging utilization appears to
      have slowed in recent years, a finding of potential interest to policy-makers and
      payers.

PMID- 24279726
TI  - Efficiency above the Shockley-Queisser limit by using nanophotonic effects to
      create multiple effective bandgaps with a single semiconductor.
AB  - We present a pure photonic approach to overcome the Shockley-Queisser limit. A
      single material can show different effective bandgap, set by its absorption
      spectrum, which depends on its photonic structure. In a tandem cell configuration
      constructed from a single material, one can achieve two different effective
      bandgaps, thereby exceeding the Shockley-Queisser limit. 

PMID- 24279725
TI  - Gene correction of human induced pluripotent stem cells repairs the cellular
      phenotype in pulmonary alveolar proteinosis.
AB  - RATIONALE: Hereditary pulmonary alveolar proteinosis (hPAP) caused by granulocyte
      macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain (CSF2RA)
      deficiency is a rare, life-threatening lung disease characterized by accumulation
      of proteins and phospholipids in the alveolar spaces. The disease is caused by a
      functional insufficiency of alveolar macrophages, which require GM-CSF signaling
      for terminal differentiation and effective degradation of alveolar proteins and
      phospholipids. Therapeutic options are extremely limited, and the pathophysiology
      underlying the defective protein degradation in hPAP alveolar macrophages remains
      poorly understood. OBJECTIVES: To further elucidate the cellular mechanisms
      underlying hPAP and evaluate novel therapeutic strategies, we here investigated
      the potential of hPAP patient-derived induced pluripotent stem cell (PAP-iPSCs)
      derived monocytes and macrophages. METHODS: Patient-specific PAP-iPSCs were
      generated from CD34(+) bone marrow cells of a CSF2RA-deficient patient with PAP.
      We assessed pluripotency, chromosomal integrity, and genetic correction of
      established iPSC lines. On hematopoietic differentiation, genetically corrected
      or noncorrected monocytes and macrophages were investigated in GM-CSF-dependent
      assays. MEASUREMENTS AND MAIN RESULTS: Although monocytes and macrophages
      differentiated from noncorrected PAP-iPSCs exhibited distinct defects in GM-CSF
      dependent functions, such as perturbed CD11b activation, phagocytic activity, and
      STAT5 phosphorylation after GM-CSF exposure and lack of GM-CSF uptake, these
      defects were fully repaired on lentiviral gene transfer of a codon-optimized
      CSF2RA-cDNA. CONCLUSIONS: These data establish PAP-iPSC-derived monocytes and
      macrophages as a valid in vitro disease model of CSF2RA-deficient PAP, and
      introduce gene-corrected iPSC-derived monocytes and macrophages as a potential
      autologous cell source for innovative therapeutic strategies. Transplantation of
      such cells to patients with hPAP could serve as a paradigmatic proof for the
      potential of iPSC-derived cells in clinical gene therapy.

PMID- 24279727
TI  - Structural basis for arabinoxylo-oligosaccharide capture by the probiotic
      Bifidobacterium animalis subsp. lactis Bl-04.
AB  - Glycan utilization plays a key role in modulating the composition of the gut
      microbiota, but molecular insight into oligosaccharide uptake by this microbial
      community is lacking. Arabinoxylo-oligosaccharides (AXOS) are abundant in the
      diet, and are selectively fermented by probiotic bifidobacteria in the colon.
      Here we show how selectivity for AXOS uptake is established by the probiotic
      strain Bifidobacterium animalis subsp. lactis Bl-04. The binding protein BlAXBP,
      which is associated with an ATP-binding cassette (ABC) transporter that mediates
      the uptake of AXOS, displays an exceptionally broad specificity for arabinosyl
      decorated and undecorated xylo-oligosaccharides, with preference for tri- and
      tetra-saccharides. Crystal structures of BlAXBP in complex with four different
      ligands revealed the basis for this versatility. Uniquely, the protein was able
      to recognize oligosaccharides in two opposite orientations, which facilitates the
      optimization of interactions with the various ligands. Broad substrate
      specificity was further enhanced by a spacious binding pocket accommodating
      decorations at different mainchain positions and conformational flexibility of a
      lid-like loop. Phylogenetic and genetic analyses show that BlAXBP is highly
      conserved within Bifidobacterium, but is lacking in other gut microbiota members.
      These data indicate niche adaptation within Bifidobacterium and highlight the
      metabolic syntrophy (cross-feeding) among the gut microbiota.

PMID- 24279728
TI  - Interplay of the fungal sumoylation network for control of multicellular
      development.
AB  - The role of the complex network of the ubiquitin-like modifier SumO in fungal
      development was analysed. SumO is not only required for sexual development but
      also for accurate induction and light stimulation of asexual development. The
      Aspergillus nidulans COMPASS complex including its subunits CclA and the
      methyltransferase SetA connects the SumO network to histone modification. SetA is
      required for correct positioning of aerial hyphae for conidiophore and asexual
      spore formation. Multicellular fungal development requires sumoylation and
      desumoylation. This includes the SumO processing enzyme UlpB, the E1 SumO
      activating enzyme AosA/UbaB, the E2 conjugation enzyme UbcN and UlpA as major
      SumO isopeptidase. Genetic suppression analysis suggests a connection between the
      genes for the Nedd8 isopeptidase DenA and the SumO isopeptidase UlpA and
      therefore a developmental interplay between neddylation and sumoylation in fungi.
      Biochemical evidence suggests an additional connection of the fungal SumO network
      with ubiquitination. Members of the cellular SumO network include histone
      modifiers, components of the transcription, RNA maturation and stress response
      machinery, or metabolic enzymes. Our data suggest that the SumO network controls
      specific temporal and spatial steps in fungal differentiation. 

PMID- 24279729
TI  - Exploring signal transduction in heteromultimeric protein based on energy
      dissipation model.
AB  - Dynamic intersubunit interactions are key elements in the regulation of many
      biological systems. A better understanding of how subunits interact with each
      other and how their interactions are related to dynamic protein structure is a
      fundamental task in biology. In this paper, a heteromultimeric allosteric
      protein, Corynebacterium glutamicum aspartokinase, is used as a model system to
      explore the signal transduction involved in intersubunit interactions and
      allosteric communication with an emphasis on the intersubunit signaling process.
      For this purpose, energy dissipation simulation and network construction are
      conducted for each subunit and the whole protein. Comparison with experimental
      results shows that the new approach is able to predict all the mutation sites
      that have been experimentally proved to desensitize allosteric regulation of the
      enzyme. Additionally, analysis revealed that the function of the effector
      threonine is to facilitate the binding of the two subunits without contributing
      to the allosteric communication. During the allosteric regulation upon the
      binding of the effector lysine, signals can be transferred from the beta-subunit
      to the catalytic site of the alpha-subunit through both a direct way of
      intersubunit signal transduction, and an indirect way: first, to the regulatory
      region of the alpha-subunit by intersubunit signal transduction and then to the
      catalytic region by intramolecular signal transduction. Therefore, the new
      approach is able to illustrate the diversity of the underlying mechanisms when
      the strength of feedback inhibition by the effector(s) is modulated, providing
      useful information that has potential applications in engineering
      heteromultimeric allosteric regulation. 

PMID- 24279731
TI  - Extremely bright full color alternating current electroluminescence of solution
      blended fluorescent polymers with self-assembled block copolymer micelles.
AB  - Electroluminescent (EL) devices operating at alternating current (AC) electricity
      have been of great interest due to not only their unique light emitting mechanism
      of carrier generation and recombination but also their great potential for
      applications in displays, sensors, and lighting. Despite great success of AC-EL
      devices, most device properties are far from real implementation. In particular,
      the current state-of-the art brightness of the solution-processed AC-EL devices
      is a few hundred candela per square meter (cd m(-2)) and most of the works have
      been devoted to red and white emission. In this manuscript, we report extremely
      bright full color polymer AC-EL devices with brightness of approximately 2300,
      6000, and 5000 cd m(-2) for blue (B), green (G), and red (R) emission,
      respectively. The high brightness of blue emission was attributed to individually
      networked multiwalled carbon nanotubes (MWNTs) for the facile carrier injection
      as well as self-assembled block copolymer micelles for suppression of interchain
      nonradiative energy quenching. In addition, effective FRET from a solution
      blended thin film of B-G and B-G-R fluorescent polymers led to very bright green
      and red EL under AC voltage, respectively. The solution-processed AC-EL device
      also worked properly with vacuum-free Ag paste on a mechanically flexible polymer
      substrate. Finally, we successfully demonstrated the long-term operation
      reliability of our AC-EL device for over 15 h. 

PMID- 24279730
TI  - Frequent falling and motor vehicle collision involvement of older drivers.
AB  - OBJECTIVES: To examine the relationship between frequent falls in older drivers
      and motor vehicle collision (MVC) involvement. DESIGN: Cross-sectional. SETTING:
      North central Alabama. PARTICIPANTS: Population-based sample of 2,000 licensed
      drivers aged 70 and older. MEASUREMENTS: Self-reported history of falling two or
      more times in the prior year was the main predictor. Outcomes were any MVC or at
      fault MVC in the prior year. RESULTS: Approximately 9% of older drivers reported
      having fallen two or more times in the prior year. Logistic regression models
      indicated that frequent falling was associated with having any MVC (crude odds
      ratio (OR) = 1.53, 95% confidence interval (CI) = 0.77-3.02) and an at-fault MVC
      (OR = 2.21, 95% CI = 0.97-5.06). Adjustment for the potentially confounding
      effects of demographic, health, visual, and driving characteristics did not
      meaningfully affect the association with any MVC, whereas the association with at
      fault MVC was weakened (adjusted OR = 2.03, 95% CI = 0.84-4.90). CONCLUSION:
      Frequent falling was associated with at-fault MVC involvement of older drivers,
      especially whites. History of falling can be used to identify individuals at risk
      of MVC involvement and to begin a dialogue about driver safety.

PMID- 24279732
TI  - Serum levels of renin-angiotensin system components in acute stroke patients.
AB  - AIM: The renin-angiotensin system (RAS) is involved in the pathogenesis of
      ischemic brain damage, and is suggested to have therapeutic potential in stroke
      by large clinical trials. However, the changes of serum RAS components in
      patients with acute stroke are totally unknown. We assessed the serum levels of
      RAS components in acute stroke patients, and investigated the relationship
      between RAS and stroke subtype. METHODS: Levels of angiotensin-converting enzyme
      (ACE), ACE2 and angiotensin II in serum from patients with acute stroke (n=117;
      male 75, female 42, age 69 +/- 13 years) were measured by an established enzyme
      linked immunosorbent assay method. Diagnosis of subtypes of ischemic stroke was
      based on the Trial of Org10172 in Acute Stroke Treatment classification. The
      Kruskal-Wallis test with post-hoc Mann-Whitney U-test with Bonferroni correction
      was carried out for statistical analysis. RESULTS: Classification of stroke was
      as follows: large-artery atherosclerosis (n=44), cardioembolism (n=33), small
      vessel occlusion (n=31), stroke of other determined etiology (n=9). Levels of
      angiotensin II and ACE did not show significant differences among each group.
      However, serum ACE2 level was significantly higher in the cardioembolism group
      than in the small-vessel occlusion group (cardioembolism 13 +/- 9.3 ng/mL, large
      artery atherosclerosis 10.2 +/- 6.8 ng/mL, small-vessel occlusion 7.2 +/- 3.7
      ng/mL, stroke of other determined etiology 10.2 +/- 7.3 ng/mL). ACE2 level showed
      a positive correlation with serum brain natriuretic peptide level (P=0.031). In
      contrast, angiotensin II concentration showed a negative correlation with
      National Institute of Health Stroke Scale score on admission (P=0.023).
      CONCLUSIONS: These findings suggest that changes of serum RAS components could
      reflect stroke subtypes and predict stroke severity.

PMID- 24279733
TI  - Purple sweet potato colour--a potential therapy for galactosemia?
AB  - Galactosemia is an inherited metabolic disease in which galactose is not properly
      metabolised. There are various theories to explain the molecular pathology, and
      recent experimental evidence strongly suggests that oxidative stress plays a key
      role. High galactose diets are damaging to experimental animals and oxidative
      stress also plays a role in this toxicity which can be alleviated by purple sweet
      potato colour (PSPC). This plant extract is rich in acetylated anthocyanins which
      have been shown to quench free radical production. The objective of this
      Commentary is to advance the hypothesis that PSPC, or compounds therefrom, may be
      a viable basis for a novel therapy for galactosemia.

PMID- 24279734
TI  - Jordanian nurses' knowledge and responsibility for enteral nutrition in the
      critically ill.
AB  - BACKGROUND: Poor nursing adherence to evidence-based guidelines has negative
      consequences leading to higher mortality rates, delayed recovery and longer
      length of stay. Evidence-based practice has the potential to minimize
      complications and discrepancies between nurses. AIM: This study aimed to assess
      nurses' practice and perception of their knowledge and responsibility in relation
      to enteral nutrition (EN) in the critically ill. DESIGN AND METHODS: This
      descriptive correlational design was applied to nurses working in intensive care
      units (ICUs) from three health care sectors in Jordan (Governmental, Military and
      Private sectors). Nurses were recruited using a stratified sampling technique. A
      pre-prepared questionnaire focusing on nurses' practice and perception towards EN
      was used. RESULTS: A total of 253 ICU nurses completed the questionnaire. Nurses
      revealed a tendency to undertake nutritional care despite the recognition
      clinical nutrition is a secondary role. In terms of nursing processes, nurses
      showed greater levels of knowledge and responsibility for 'preventing
      complications' and 'evaluation' more than 'assessment' and 'identifying goals'.
      Nurses inadequately assess both gastric residuals and tube placement before
      feeding. Diarrhoea was the most frequent complication followed by abdominal pain,
      vomiting, tube dislodgment and weight loss. However, nurses realized that the
      incidences of complications is less likely when applying evidence-based protocol.
      CONCLUSION: It is necessary to establish a preliminary assessment for patients'
      nutritional needs prior to using EN. Aspiration reduction measures are still
      deficient and need further attention. An evidence-based protocol for EN should be
      adopted in the critically ill. RELEVANCE TO CLINICAL PRACTICE: This article
      provides insight into the current practice of Jordanian intensive care nurses in
      different health care sectors. The study can contribute to redirect the
      perception of nurses towards nutrition in the critically ill in addition to
      enhance positive adherence to evidence base.

PMID- 24279735
TI  - Enhancement of rutin production in Fagopyrum tataricum hairy root cultures with
      its endophytic fungal elicitors.
AB  - Tartary buckwheat (Fagopyrum tataricum) is a potentially important source of
      rutin, a natural bioactive flavonoid with antihyperglycemic, antioxidative,
      antihypertensive, and anti-inflammatory properties. This study examines the
      effects of endophytic fungi on rutin production in the hairy root cultures of F.
      tataricum. Without obvious changes in the appearance of the hairy roots, the
      exogenous fungal mycelia elicitors efficiently stimulated the hairy root growth
      and rutin biosynthesis, and the stimulation effect was mainly dependent on the
      mycelia elicitor species, as well as its treatment dose. Two endophytic fungal
      isolates Fat9 (Fusarium oxysporum) and Fat15 (Alternaria sp.) were screened as
      promising candidates for promoting F. tataricum hairy root growth and rutin
      production. With application of polysaccharide (PS) of endophyte Fat9 (200 mg/L),
      and PS of endophyte Fat15 (100 mg/L) to the hairy root cultures on day 25, the
      rutin yield was increased to 45.9 mg/L and 47.2 mg/L, respectively. That was
      about 3.1- to 3.2-fold in comparison with the control level of 14.6 mg/L.
      Moreover, the present study revealed that the accumulation of rutin resulted from
      the stimulation of the phenylpropanoid pathway by mycelia PS treatments. This may
      be an efficient strategy for enhancing rutin production in F. tataricum hairy
      root culture provided with its endophytic mycelia elicitors.

PMID- 24279737
TI  - Percentage and determinants of missed HIV testing in pregnancy: a survey of women
      delivering in the Lazio region, Italy.
AB  - HIV testing is recommended as part of routine preconception and prenatal care but
      some cases of vertical transmission still occur because of missed HIV testing in
      pregnancy. We estimated the percentage of women missing HIV testing before
      delivery, and we evaluated factors related with it. An anonymous survey was
      distributed to women giving birth during a two-week period in the maternity units
      of hospitals in the Lazio region of Italy in 2011. Among the 1568 women who
      filled out the questionnaire, only 33.6% had an HIV test prior to conception,
      while 88.2% were tested during pregnancy; main reasons reported for missed
      testing were: not requested by the gynaecologist (57.0%), performed previously
      (20.7%), requested by the gynaecologist but not done (13.3%) and
      structural/organisational barriers (4.4%). The percentage of women who missed the
      HIV test as part of preconception care or during pregnancy was 9.1% (95%
      confidence interval, CI: 7.7-10.6). Multivariate analysis showed that those with
      missed test were younger (p = 0.05), of lower education level (p < 0.01), with a
      lower HIV-knowledge score (p < 0.01) and with fewer visits during pregnancy (p <
      0.01). Around 10% of delivering women were not tested for HIV during pregnancy or
      as part of preconception care. Absence of a specific request by the gynaecologist
      was the most frequent reason given. The association of missed HIV testing with
      poor sociocultural level and limited maternal HIV knowledge emphasise the
      importance of promoting HIV information among women and prenatal care providers.
      Strategies to increase routine testing may include the adoption of an opt-out
      approach. Finally, availability of rapid HIV testing in the delivery room should
      be encouraged.

PMID- 24279736
TI  - A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic
      pain.
AB  - Pregabalin is a commonly used therapy currently recommended as first-line
      treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a
      number of clinical trials of pregabalin in different NeP conditions have been
      completed from which additional data on safety and tolerability can be drawn. In
      this analysis, patient-level data from 31 randomized clinical trials of
      pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for
      incidence of adverse events (AEs). Incidence by age, disease condition, and race,
      together with risk differences and time to onset and resolution of AEs, was
      assessed. In total, 7,510 patients were included: 4,884 on pregabalin
      (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs.
      placebo risk analysis identified 9 AEs with a risk difference, for which the
      lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk
      difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]),
      peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry
      mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2
      [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2
      to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within
      the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without
      resulting in cessation of treatment. The data from this review provide
      information, indicating which AEs may be expected in patients treated with
      pregabalin, and suggest that careful dose titration to the highest tolerable dose
      is the most appropriate approach in clinical practice.

PMID- 24279739
TI  - The development of evidence-based prehospital guidelines using a GRADE-based
      methodology.
AB  - BACKGROUND: The burgeoning literature in prehospital care creates an opportunity
      to improve care through evidence-based guidelines (EBGs). Previously, an
      established process for the creation of such guidelines and adoption and
      implementation at the local level was lacking. This has led to great variability
      in the content of prehospital protocols in different jurisdictions across the
      globe. Recently the Federal Interagency Committee on Emergency Medical Services
      (FICEMS) and the National EMS Advisory Council (NEMSAC) approved a National
      Prehospital Evidence-based Guideline Model Process for the development,
      implementation, and evaluation of EBGs. The Model Process recommends the use of
      established guideline development tools such as Grading of Recommendations,
      Assessment, Development, and Evaluation (GRADE). Objective. To describe the
      process of development of three prehospital EBGs using the National Prehospital
      EBG Model Process (EBG Model Process) and the GRADE EBG development tool.
      METHODS: We conducted three unique iterations of the EBG Model Process utilizing
      the GRADE EBG development tool. The process involved 6 distinct and essential
      steps, including 1) assembling the expert panel and providing GRADE training; 2)
      defining the evidence-based guideline (EBG) content area and establishing the
      specific clinical questions to address in patient, intervention, comparison, and
      outcome (PICO) format; 3) prioritizing outcomes to facilitate systematic
      literature searches; 4) creating GRADE tables, or evidence profiles, for each
      PICO question; 5) vetting and endorsing GRADE evidence tables and drafting
      recommendations; and 6) synthesizing recommendations into an EMS protocol and
      visual algorithm. Feedback and suggestions for improvement were solicited from
      participants and relevant stakeholders in the process. RESULTS: We successfully
      used the process to create three separate prehospital evidence-based guidelines,
      formatted into decision tree algorithms with levels of evidence and graded
      recommendations assigned to each decision point. However, the process revealed
      itself to be resource intensive, and most of the suggestions for improvement
      would require even more resource utilization. CONCLUSIONS: The National
      Prehospital EBG Model Process can be used to create credible, transparent, and
      usable prehospital evidence-based guidelines. We suggest that a centralized or
      regionalized approach be used to create and maintain a full set of prehospital
      EBGs as a means of optimizing resource use.

PMID- 24279738
TI  - A randomized 3*3 crossover study to evaluate the effect of Hass avocado intake on
      post-ingestive satiety, glucose and insulin levels, and subsequent energy intake
      in overweight adults.
AB  - BACKGROUND: The behavioral outcome of food ingestion is a complex process that
      involves psychological and biological factors. Avocados are nutrient dense with
      properties that may favorably impact energy balance. This study sought to
      evaluate if incorporating approximately one half of a Hass avocado by addition or
      inclusion into a lunch meal will influence post-ingestive satiety, glucose and
      insulin response, and subsequent energy intake among overweight adults. METHODS:
      This was a randomized 3*3 single-blind crossover design study with 26 healthy
      overweight adults (mean +/-SD age 40.8+/-11.0 years and BMI 28.1+/-2.4 kg/m2).
      Participants consumed a standardized breakfast followed by 1 of 3 lunch test
      meals [Control (C), avocado-free; Avocado Inclusive (AI); and, Avocado Added
      (AA)]. Participants rated five appetite sensations using a visual analog scale
      (VAS) before lunch and at specific intervals over 5 hours following the start of
      the test meal. Blood glucose and insulin were measured before lunch and at
      specific intervals over 3 hours following the start of the test meal. Mixed
      models were used to compare differences among the 3 test meals, and the area
      under the curve (AUC(0-xh)) was computed for the VAS and biological measures.
      RESULTS: There were significant differences in the AUC(0-5h) for the self
      reported feelings of satisfaction (P=0.04) and desire to eat (P=0.05) in the
      mixed model analysis. Compared to the C test meal, the AA test meal increased
      satisfaction by 23% (P=0.05) and decreased the desire to eat by 28% (P=0.04) for
      the AUC(0-5h). For the AUC(0-3h), the AA test meal increased satisfaction by 26%
      (P=0.02) and decreased the desire to eat by 40% (P=0.01) as compared to the C
      test meal. Compared to the AI meal, the AUC(0-3h) for blood insulin was higher in
      the C and AA meals (P=0.04 and P=0.05, respectively). CONCLUSIONS: The addition
      of approximately one half of a Hass avocado at a lunch meal can influence post
      ingestive satiety over a subsequent 3 and 5 hour period in overweight adults. A
      caveat to these findings is that the avocado contained an additional 112 kcal,
      which may have accounted for the observed increase in satisfaction and decreased
      desire to eat. Future trials are warranted to evaluate the effects of avocado
      intake on weight management in adults of varying BMIs and among insulin resistant
      individuals.

PMID- 24279740
TI  - A predicted protein interactome for rice.
AB  - BACKGROUND: Protein-protein interactions (PPIs) create the steps in signaling and
      regulatory networks central to most fundamental biological processes. It is
      possible to predict these interactions by making use of experimentally determined
      orthologous interactions in other species. RESULTS: In this study, prediction of
      PPIs in rice was carried out by the interolog method of mapping deduced
      orthologous genes to protein interactions supported by experimental evidence from
      reference organisms. We predicted 37112 interactions for 4567 rice proteins,
      including 1671 predicted self interactions (homo-interactions) and 35441
      predicted interactions between different proteins (hetero-interactions). These
      matched 168 of 675 experimentally-determined interactions in rice. Interacting
      proteins were significantly more co-expressed than expected by chance, which is
      typical of experimentally-determined interactomes. The rice interacting proteins
      were divided topologically into 981 free ends (proteins with single
      interactions), 499 pipes (proteins with two interactions) and 3087 hubs of
      different sizes ranging from three to more than 100 interactions. CONCLUSIONS:
      This predicted rice interactome extends known pathways and improves functional
      annotation of unknown rice proteins and networks in rice, and is easily explored
      with software tools presented here.

PMID- 24279741
TI  - Bioactive properties of the main triterpenes found in olives, virgin olive oil,
      and leaves of Olea europaea.
AB  - Oleanolic acid, maslinic acid, uvaol, and erythrodiol are the main triterpenes
      present in olives, olive tree leaves, and virgin olive oil. Their concentration
      in virgin olive oil depends on the quality of the olive oil and the variety of
      the olive tree. These triterpenes are described to present different properties,
      such as antitumoral activity, cardioprotective activity, anti-inflammatory
      activity, and antioxidant protection. Olive oil triterpenes are a natural source
      of antioxidants that could be useful compounds for the prevention of multiple
      diseases related to cell oxidative damage. However, special attention has to be
      paid to the concentrations used, because higher concentration may lead to
      cytotoxic or biphasic effects. This work explores all of the bioactive properties
      so far described for the main triterpenes present in virgin olive oil. 

PMID- 24279742
TI  - Pelvic floor muscle activity, quality of life, and sexual function in peri- and
      recently postmenopausal women with and without dyspareunia: a cross-sectional
      study.
AB  - Pelvic floor alterations during menopausal years, resulting from aging and
      hormonal decline, may lead to several forms of sexual dysfunction. Dyspareunia
      pain during sexual intercourse-is among the most frequent. Nevertheless, few
      studies so far have evaluated pelvic floor muscle function in postmenopausal
      women with dyspareunia. The authors thus carried out a cross-sectional study to
      assess myoelectric activity in pelvic floor muscles in peri- and postmenopausal
      women with and without dyspareunia receiving routine care at an outpatient
      clinic. In addition, sexual function (using the Female Sexual Function Index) and
      quality of life (using the Cervantes Scale) were assessed. Fifty-one peri- and
      postmenopausal women between 45 to 60 years of age (M = 52.1, SD = 4.9) were
      evaluated, 27 with and 24 without dyspareunia. There were no statistically
      significant differences in resting muscle activity, maximal voluntary
      contraction, and sustained contraction between women with and without
      dyspareunia. There were statistically significant between-group differences on
      the Cervantes Scale (p =.009) and in all Female Sexual Function Index domains
      except desire and satisfaction (arousal, p =.019; lubrication, p =.030; orgasm, p
      =.032; pain, p <.001; desire, p =.061; satisfaction, p =.081), indicating that
      women with dyspareunia experience worse quality of life and less satisfactory
      sexual function as compared with women without dyspareunia. 

PMID- 24279744
TI  - Biomimetic poly(serinol hexamethylene urea) for promotion of neurite outgrowth
      and guidance.
AB  - Nerve function recovery is a major technical challenge in the rehabilitation of
      patients suffering from severe neuropathies. Facilitating functional recovery
      requires the creation of a growth-permissive environment that directs the
      extension and myelination of surviving neurons. To this end, an electrospun
      nanofiber scaffold composed of arginine-glycine-aspartate-modified poly(serinol
      hexamethylene urea)-blend-poly-epsilon-caprolactone (PSHU-RGD/PCL) has been
      employed. Initially, we investigated the cytotoxicity of PSHU in PC12 cell
      culture. This was followed by functional examinations of PSHU-RGD for cell
      viability, proliferation, differentiation, and neurite outgrowth, and finally we
      examined electrospun scaffolds for guided neurite sprouting. MTT proliferation
      assays indicated no cytotoxic effects of polymer as compared to laminin-coated
      surfaces. Functional testing revealed PSHU-RGD surfaces to be comparable to the
      positive control, laminin-coated surface, in neurite outgrowth studies with
      average neurite lengths of 84.6 MUm (laminin), 218.2 MUm (PSHU-RGD), 570.2 MUm
      (laminin + NGF), and 958.2 MUm (PSHU-RGD + NGF) after two weeks on homogeneously
      modified surfaces, and 554.8 MUm (nonwoven mats) and 1512.3 MUm (uniaxially
      aligned mats) for PSHU-RGD/PCL + NGF scaffolds after one week. We created PSHU
      functionalized with the tripeptide, RGD, which provided chemical and physical
      cues to PC12 cell proliferation and differentiation. We expect that PSHU-RGD will
      be capable of directing and promoting neurite outgrowth in many neuropathy
      models.

PMID- 24279743
TI  - In utero and early life exposure to diesel exhaust air pollution increases adult
      susceptibility to heart failure in mice.
AB  - BACKGROUND: Fine particulate air pollution (PM2.5) is a global health concern, as
      exposure to PM2.5 has consistently been found to be associated with increased
      cardiovascular morbidity and mortality. Although adult exposure to traffic
      related PM2.5, which is largely derived from diesel exhaust (DE), has been
      associated with increased cardiac hypertrophy, there are limited investigations
      into the potential effect of in utero and early life exposure on adult
      susceptibility to heart disease. In this study, we investigate the effect of in
      utero and early life exposure to DE on adult susceptibility to heart failure.
      METHODS: Female C57BL/6 J mice were exposed to either filtered air (FA) or DE for
      3 weeks (~ 300 MUg/m3 PM2.5 for 6 hours/day, 5 days/week) and then introduced to
      male breeders for timed matings. Female mice were exposed to either FA or DE
      throughout pregnancy and until offspring were 3 weeks of age. Offspring were then
      transferred to either FA or DE for an additional 8 weeks of exposure. At 12 weeks
      of age, male offspring underwent a baseline echocardiographic assessment,
      followed by a sham or transverse aortic constriction (TAC) surgery to induce
      pressure overload. Following sacrifice three weeks post surgery, ventricles were
      processed for histology to assess myocardial fibrosis and individual
      cardiomyocyte hypertrophy. mRNA from lung tissue was isolated to measure
      expression of inflammatory cytokines IL6 and TNFalpha. RESULTS: We observed that
      mice exposed to DE during in utero and early life development have significantly
      increased susceptibility to cardiac hypertrophy, systolic failure, myocardial
      fibrosis, and pulmonary congestion following TAC surgery compared to FA control,
      or adult DE exposed mice. In utero and early life DE exposure also strongly
      modified the inflammatory cytokine response in the adult lung. CONCLUSIONS: We
      conclude that exposure to diesel exhaust air pollution during in utero and early
      life development in mice increases adult susceptibility to heart failure. The
      results of this study may imply that the effects of air pollution on
      cardiovascular disease in human populations may be strongly mediated through a
      'fetal origins' of adult disease pathway. Further investigations on this
      potential pathway of disease are warranted.

PMID- 24279745
TI  - In vitro effectiveness of the antimicrobial peptide eCATH1 against antibiotic
      resistant bacterial pathogens of horses.
AB  - The equine antimicrobial peptide eCATH1 previously has been shown to have in
      vitro activity against antibiotic-susceptible reference strains of Rhodococcus
      equi and common respiratory bacterial pathogens of foals. Interestingly, eCATH1
      was also found to be effective in the treatment of R. equi infection induced in
      mice. The aim of this study was to assess the in vitro activity of eCATH1 against
      equine isolates of Gram-negative (Escherichia coli, Salmonella enterica,
      Klebsiella pneumoniae and Pseudomonas spp.) and Gram-positive (R. equi,
      Staphylococcus aureus) bacteria resistant to multiple classes of conventional
      antibiotics. A modified microdilution method was used to evaluate the minimum
      inhibitory concentrations (MICs) of the antimicrobial peptide. The study revealed
      that eCATH1 was active against all equine isolates of E. coli, S. enterica, K.
      pneumoniae, Pseudomonas spp. and R. equi tested, with MICs of 0.5-16 MUg mL(-1),
      but was not active against most isolates of S. aureus. In conclusion, the
      activity of the equine antimicrobial peptide eCATH1 appears to not be hampered by
      the antibiotic resistance of clinical isolates. Thus, the data suggest that
      eCATH1 could be useful, not only in the treatment of R. equi infections, but also
      of infections caused by multidrug-resistant Gram-negative pathogens.

PMID- 24279746
TI  - Evaluation of intestinal permeability of vicenin-2 and lychnopholic acid from
      Lychnophora salicifolia (Brazilian arnicao) using Caco-2 cells.
AB  - Lychnophora salicifolia, commonly known as "arnicao", is used as an anti
      inflammatory agent and as a flavoring agent in the Brazilian traditional spirit
      "cachaca". In this work, the permeation process of vicenin-2 (1) and lychnopholic
      acid (2) (major secondary metabolites from the hydroalcoholic extract) was
      investigated using Caco-2 cells. For this investigation, a new HPLC-DAD method
      was developed and validated for the quantification step. It was observed that 2
      crosses the Caco-2 cell monolayer by passive diffusion. On the other hand, 1 was
      not transported, suggesting no absorption and no efflux of this compound in Caco
      2 cells. 

PMID- 24279747
TI  - Effects of a six-month intradialytic physical ACTIvity program and adequate
      NUTritional support on protein-energy wasting, physical functioning and quality
      of life in chronic hemodialysis patients: ACTINUT study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Protein-energy wasting (PEW) is common in hemodialysis patients and
      is a powerful predictor of morbidity and mortality. Although much progress has
      been made in recent years in identifying the causes and pathogenesis of PEW in
      hemodialysis patients, actual management by nutritional interventions is not
      always able to correct PEW. Some investigators suggest that physical exercise may
      increase the anabolic effects of nutritional interventions, and therefore may
      have a potential to reverse PEW. The aim of this study is to investigate the
      effect of intra-dialytic progressive exercise training and adequate nutritional
      supplementation on markers of PEW, functional capacities and quality of life of
      adult hemodialysis patients. METHODS AND DESIGN: Fifty end-stage renal disease
      patients undergoing hemodialysis, who meet the diagnostic criteria for PEW, will
      be randomly allocated into an exercise or control group for 6 months. The
      exercise consists of a progressive submaximal individualized cycling exertion
      using an adapted cycle ergometer, during the three weekly dialysis sessions.
      Biological markers of nutrition (albumin, prealbumin) will be followed monthly
      and all patients will be assessed for body composition, walk function, muscle
      strength, postural stability and quality of life at baseline and during the
      eighth week (t+2), the sixteenth week (t+4) and the twenty-fourth week (t+6) of
      the 6-month adapted rehabilitation program. DISCUSSION: The successful completion
      of this current trial may give precious clues in understanding PEW and encourage
      nephrologists to extend prescription of exercise programs as well as therapeutic
      and as preventive interventions in this high-risk population. TRIAL REGISTRATION:
      The protocol for this study was registered with the France Clinical Trials
      Registry NCT01813851.

PMID- 24279748
TI  - Nutritional modulation of cataract.
AB  - Lens opacification or cataract reduces vision in over 80 million people worldwide
      and blinds 18 million. These numbers will increase dramatically as both the size
      of the elderly demographic and the number of those with carbohydrate metabolism
      related problems increase. Preventative measures for cataract are critical
      because the availability of cataract surgery in much of the world is
      insufficient. Epidemiologic literature suggests that the risk of cataract can be
      diminished by diets that are optimized for vitamin C, lutein/zeaxanthin, B
      vitamins, omega-3 fatty acids, multivitamins, and carbohydrates: recommended
      levels of micronutrients are salutary. The limited data from intervention trials
      provide some support for observational studies with regard to nuclear - but not
      other types of - cataracts. Presented here are the beneficial levels of nutrients
      in diets or blood and the total number of participants surveyed in epidemiologic
      studies since a previous review in 2007. 

PMID- 24279749
TI  - Antioxidant activity of herbaceous plant extracts protect against hydrogen
      peroxide-induced DNA damage in human lymphocytes.
AB  - BACKGROUND: Herbaceous plants containing antioxidants can protect against DNA
      damage. The purpose of this study was to evaluate the antioxidant substances,
      antioxidant activity, and protection of DNA from oxidative damage in human
      lymphocytes induced by hydrogen peroxide (H2O2). Our methods used acidic methanol
      and water extractions from six herbaceous plants, including Bidens alba (BA),
      Lycium chinense (LC), Mentha arvensis (MA), Plantago asiatica (PA), Houttuynia
      cordata (HC), and Centella asiatica (CA). METHODS: Antioxidant compounds such as
      flavonol and polyphenol were analyzed. Antioxidant activity was determined by the
      inhibition percentage of conjugated diene formation in a linoleic acid emulsion
      system and by trolox-equivalent antioxidant capacity (TEAC) assay. Their
      antioxidative capacities for protecting human lymphocyte DNA from H2O2-induced
      strand breaks was evaluated by comet assay. RESULTS: The studied plants were
      found to be rich in flavonols, especially myricetin in BA, morin in MA, quercetin
      in HC, and kaemperol in CA. In addition, polyphenol abounded in BA and CA. The
      best conjugated diene formation inhibition percentage was found in the acidic
      methanolic extract of PA. Regarding TEAC, the best antioxidant activity was
      generated from the acidic methanolic extract of HC. Water and acidic methanolic
      extracts of MA and HC both had better inhibition percentages of tail DNA% and
      tail moment as compared to the rest of the tested extracts, and significantly
      suppressed oxidative damage to lymphocyte DNA. CONCLUSION: Quercetin and morin
      are important for preventing peroxidation and oxidative damage to DNA, and the
      leaves of MA and HC extracts may have excellent potential as functional
      ingredients representing potential sources of natural antioxidants.

PMID- 24279750
TI  - Lactococcus lactis YfiA is necessary and sufficient for ribosome dimerization.
AB  - Dimerization and inactivation of ribosomes in Escherichia coli is a two-step
      process that involves the binding of ribosome modulation factor (RMF) and
      hibernation promotion factor (HPF). Lactococcus lactis MG1363 expresses a
      protein, YfiA(L) (l) , which associates with ribosomes in the stationary phase of
      growth and is responsible for dimerization of ribosomes. We show that full-length
      YfiA(L) (l) is necessary and sufficient for ribosome dimerization in L. lactis
      but also functions heterologously in vitro with E. coli ribosomes. Deletion of
      the yfiA gene has no effect on the growth rate but diminishes the survival of L.
      lactis under energy-starving conditions. The N-terminal domain of YfiA(L) (l) is
      homologous to HPF from E. coli, whereas the C-terminal domain has no counterpart
      in E. coli. By assembling ribosome dimers in vitro, we could dissect the roles of
      the N- and C-terminal domains of YfiA(L) (l) . It is concluded that the
      dimerization and inactivation of ribosomes in L. lactis and E. coli differ in
      several cellular and molecular aspects. In addition, two-dimensional maps of
      dimeric ribosomes from L. lactis obtained by single particle electron microscopy
      show a marked structural difference in monomer association in comparison to the
      ribosome dimers in E. coli. 

PMID- 24279751
TI  - Two new phthalides with BuChE inhibitory activity from Ligusticum chuanxiong.
AB  - Two new phthalides, chuanxiongdiolides A and B, were isolated from the roots of
      Ligusticum chuanxiong Hort. Their structures were established by UV, IR, 1D (1H,
      13C) and 2D (HSQC, 1H-1H COSY, HMBC, NOESY) NMR, and HR-ESI-MS methods, and their
      absolute configurations were assigned via circular dichroism exciton chirality.
      The two compounds showed different degrees of inhibitory effects against
      butyrylcholine esterase.

PMID- 24279752
TI  - Use of induced pluripotent stem cells to recapitulate pulmonary alveolar
      proteinosis pathogenesis.
AB  - RATIONALE: In patients with pulmonary alveolar proteinosis (PAP) syndrome,
      disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling
      is associated with pathogenic surfactant accumulation from impaired clearance in
      alveolar macrophages. OBJECTIVES: The aim of this study was to overcome these
      barriers by using monocyte-derived induced pluripotent stem (iPS) cells to
      recapitulate disease-specific and normal macrophages. METHODS: We created iPS
      cells from two children with hereditary PAP (hPAP) caused by recessive
      CSF2RA(R217X) mutations and three normal people, differentiated them into
      macrophages (hPAP-iPS-Mphis and NL-iPS-Mphis, respectively), and evaluated
      macrophage functions with and without gene-correction to restore GM-CSF signaling
      in hPAP-iPS-Mphis. MEASUREMENTS AND MAIN RESULTS: Both hPAP and normal iPS cells
      had human embryonic stem cell-like morphology, expressed pluripotency markers,
      formed teratomas in vivo, had a normal karyotype, retained and expressed mutant
      or normal CSF2RA genes, respectively, and could be differentiated into
      macrophages with the typical morphology and phenotypic markers. Compared with
      normal, hPAP-iPS-Mphis had impaired GM-CSF receptor signaling and reduced GM-CSF
      dependent gene expression, GM-CSF- but not M-CSF-dependent cell proliferation,
      surfactant clearance, and proinflammatory cytokine secretion. Restoration of GM
      CSF receptor signaling corrected the surfactant clearance abnormality in hPAP-iPS
      Mphis. CONCLUSIONS: We used patient-specific iPS cells to accurately reproduce
      the molecular and cellular defects of alveolar macrophages that drive the
      pathogenesis of PAP in more than 90% of patients. These results demonstrate the
      critical role of GM-CSF signaling in surfactant homeostasis and PAP pathogenesis
      in humans and have therapeutic implications for hPAP.

PMID- 24279753
TI  - Enhanced biosynthesis of poly(3-hydroxybutyrate) from potato starch by Bacillus
      cereus strain 64-INS in a laboratory-scale fermenter.
AB  - To decrease the polyhydroxyalkanoate (PHA) production cost by supplying renewable
      carbon sources has been an important aspect in terms of commercializing this
      biodegradable polymer. The production of biodegradable poly(3-hydroxyalkanoates)
      (PHA) from raw potato starch by the Bacillus cereus 64-INS strain isolated from
      domestic sludge has been studied in a lab-scale fermenter. The bacterium was
      screened for the degradation of raw potato starch by a starch hydrolysis method
      and for PHA production by Nile blue A and Sudan black B staining. Shake-flask
      cultures of the bacterium with glucose [2% (w/v)] or raw potato starch [2% (w/v)]
      produced PHA of 64.35% and 34.68% of dry cell weight (DCW), respectively. PHA
      production was also carried out in a 5-L fermenter under control conditions that
      produced 2.78 g/L of PHA and PHA content of 60.53% after 21 hr of fermentation
      using potato starch as the sole carbon source. Gas chromatography-mass
      spectroscopy (GC-MS) analyses confirmed that the extracted PHA contained poly(3
      hydroxybutyrate) (PHB) as its major constituent (>99.99%) irrespective of the
      carbon source used. The article describes, for what we believe to be the first
      time, PHB production being carried out without any enzymatic or chemical
      treatment of potato starch at higher levels by fermentation. More work is
      required to optimize the PHB yield with respect to starch feeding strategies.

PMID- 24279755
TI  - Real-time dark-field scattering microscopic monitoring of the in situ growth of
      single Ag@Hg nanoalloys.
AB  - A comprehensive understanding of the growth mechanism of nanoalloys is beneficial
      in designing and synthesizing nanoalloys with precisely tailored properties to
      extend their applications. Herein, we present the investigation in this aspect by
      real-time monitoring of the in situ growth of single Ag@Hg nanoalloys, through
      direct amalgamation of Ag nanoparticles with elemental mercury, by dark-field
      scattering microscopy. Four typically shaped Ag nanoparticles, such as rods,
      triangular bipyramids, cubes, and spheres, were used as seeds for studying the
      growth of Ag@Hg nanoalloys. The scattered light of Ag nanoparticles of different
      shapes, on exposure to the growth solution, exhibited a noticeable blue-shift
      followed by a red-shift, suggesting the growth of Ag@Hg nanoalloys. The formation
      of Ag@Hg nanoalloys was confirmed by scanning electron microscopy, high
      resolution transmit electron microscopy, X-ray diffraction, energy-dispersive X
      ray spectroscopy, and elemental mapping and line scanning. Further analysis of
      the time-dependent spectral data and morphological change of single nanoparticles
      during the growth led to the visual identification of the growth mechanism of
      single Ag@Hg nanoalloys. Three important steps were involved: first, rapid
      adsorption of Hg atoms onto Ag nanoparticles; second, initial diffusion of Hg
      atoms into Ag nanoparticles, rounding or shortening the particles; third, further
      diffusion of Hg atoms leading to the formation of spherical Ag@Hg nanoalloys. On
      the basis of these results, Ag@Hg nanoalloys with given optical properties can be
      synthesized. Moreover, dark-field scattering microscopy is expected to be a
      powerful tool used for real-time monitoring of the in situ growth of other metal
      nanoparticles. 

PMID- 24279754
TI  - The assessment and management of chronic cough in children according to the
      British Thoracic Society guidelines: descriptive, prospective, clinical trial.
AB  - BACKGROUND: Chronic cough is a common problem of various etiologies. While
      diagnosis may relatively be easy in the presence of some specific findings, it
      tends to be rather difficult when there are no clear symptoms. Therefore,
      practical guidelines are needed for management of patients with chronic cough. We
      aimed to evaluate assessment and management of chronic cough in children
      according to the British Thoracic Society guidelines published in 2008. METHODS:
      Patients with chronic cough lasting longer than 8 weeks between 5 and 16 years
      old were evaluated. Pulmonary function test and chest radiography were performed
      on all patients. Further workup was conducted on those requiring further
      investigation. Patients were re-evaluated at 2- to 4-week intervals, and we
      followed our patients for 18 months until cough resolved. RESULTS: One hundred
      fifty six patients (52.5% female) aged 5-16 (8.42 +/- 2.6) years were included.
      Of the 156 patients, 19.2% (n = 30) were diagnosed with postnasal drip syndrome
      plus asthma; 18.6% (n = 29) with postnasal drip syndrome; 12.2% (n = 19) with
      asthma; 12.2% (n = 19) with protracted bacterial bronchitis; and 11.5% (n = 18)
      with nonspecific isolated cough, 9.6% (n = 15) with cough variant asthma, 5.7% (n
      = 9) with psychogenic cough and 3.2% (n = 5) with gastroesophageal reflux
      disease. CONCLUSIONS: Postnasal drip syndrome and asthma was the most common
      cause of chronic cough. Asthma-associated findings were found in some of the
      patients diagnosed with postnasal drip syndrome. It has been observed that there
      could be more than one particular cause for cough concerning some patients. The
      gastroesophageal reflux disease was not a common primary cause of chronic cough
      in children.

PMID- 24279756
TI  - Increased activation of synapsin 1 and mitogen-activated protein
      kinases/extracellular signal-regulated kinase in the amygdala of maternal
      separation rats.
AB  - BACKGROUND: Early life stress (ELS) causes alterations in emotionality and
      anxiety levels as a significant risk factor for psychiatric problems, and these
      alterations have been associated with amygdala activity. AIMS: To elucidate the
      molecular mechanism on the development of psychiatric problems following ELS, we
      identified the alteration of molecules in the amygdala using maternal separation
      (MS; pnd 14-21) rats through gene expression and DNA methylation microarray
      analysis, and studied the involvement of candidate genes using a Western blot and
      immunohistochemistry analysis. RESULTS: Through a microarray analysis, in the
      amygdala of MS rats, we found a downregulation of mRNA expression of synapsin 1
      (Syn1) gene with hypermethylation of its transcription start site (TSS), and the
      alterations of mRNA expressions of Syn1 activation-related kinase genes including
      mitogen-activated protein kinases (Mapks) with change of their TSS methylation.
      In addition, MS increased not only Syn1 phosphorylation at the phosphorylation
      sites by Mapk/extracellular signal-regulated kinase (Erk), but also Mapk/Erk
      phosphorylation in the amygdala. Furthermore, double immunofluorescence staining
      showed that MS could elevate phospho-Mapk/Erk immunoreactivity (IR) in Syn1
      expression puncta. CONCLUSION: These findings indicated that the activation of
      Mapk/Erk and Syn1 may be a key mechanism modulating synaptic neurotransmition in
      the amygdala of MS rats.

PMID- 24279757
TI  - Development of the recombinase-based in vivo expression technology in
      Streptococcus thermophilus and validation using the lactose operon promoter.
AB  - AIMS: To construct and validate the recombinase-based in vivo expression
      technology (R-IVET) tool in Streptococcus thermophilus (ST). METHODS AND RESULTS:
      The R-IVET system we constructed in the LMD-9 strain includes the plasmid
      pULNcreB allowing transcriptional fusion with the gene of the site-specific
      recombinase Cre and the chromosomal cassette containing a spectinomycin
      resistance gene flanked by two loxP sites. When tested in M17 medium, promoters
      of the genes encoding the protease PrtS, the heat-shock protein Hsp16 and of the
      lactose operon triggered deletion of the cassette, indicating promoter activity
      in these conditions. The lactose operon promoter was also found to be activated
      during the transit in the murine gastrointestinal tract. CONCLUSIONS: The R-IVET
      system developed in ST is relatively stable, functional, very sensitive and can
      be used to assay activity of promoters, which are specifically active in in vivo
      conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This first adaptation of R-IVET
      to ST provides a highly valuable tool allowing an exploration of the
      physiological state of ST in the GIT of mammals, fermentation processes or dairy
      products.

PMID- 24279759
TI  - Local heating with lithographically fabricated plasmonic titanium nitride
      nanoparticles.
AB  - Titanium nitride is considered a promising alternative plasmonic material and is
      known to exhibit localized surface plasmon resonances within the near-infrared
      biological transparency window. Here, local heating efficiencies of disk-shaped
      nanoparticles made of titanium nitride and gold are compared in the visible and
      near-infrared regions numerically and experimentally with samples fabricated
      using e-beam lithography. Results show that plasmonic titanium nitride nanodisks
      are efficient local heat sources and outperform gold nanodisks in the biological
      transparency window, dispensing the need for complex particle geometries.

PMID- 24279758
TI  - Gender differences in functional outcome of elderly hip fracture patients.
AB  - AIM: The purpose of the present study was to investigate whether gender might
      affect functional outcome of hip fractured patients undergoing in-hospital
      rehabilitation. METHODS: This was a retrospective chart review study comprising
      of 759 consecutive elderly patients suffering traumatic hip fracture. All
      patients underwent a standard orthogeriatric care of surgical hip repair and post
      acute rehabilitation care. Functional outcome (female vs male gender) was
      assessed by motor and total Functional Independence Measurement (FIM) scores on
      discharge. Data was analyzed by t-tests chi(2) -test and multiple linear
      regression analyses. RESULTS: A total of 574 (75.6%) out of all patients were
      females. There were no differences in admission FIM scores; however, male
      patients had a higher prevalence of comorbidities. FIM scores on discharge were
      higher in female patients (motor FIM, P=0.007; motor FIM gain, P=0.001; compared
      with males). A multiple linear regression analysis showed that female gender was
      independently associated with higher total FIM at discharge (beta
      coefficient=0.056, P=0.008), higher motor FIM at discharge (beta
      coefficient=0.071, P=0.007) and higher total FIM gain at discharge (beta
      coefficient=0.11, P=0.008). CONCLUSION: The findings suggest that absolute
      discharge FIM scores of females are higher, compared with male patients. After
      adjusting for possible covariates, female gender still emerged as an independent
      predictor for higher FIM at discharge, suggesting that male gender should be
      considered as adversely affecting rehabilitation outcome of hip fracture male
      patients.

PMID- 24279760
TI  - Multiscale scattering investigations of asphaltene cluster breakup, nanoaggregate
      dissociation, and molecular ordering.
AB  - Small-angle X-ray and neutron scattering (SAXS/SANS) by asphaltenes in various
      solvents (toluene, tetrahydrofuran, and 1-methylnaphthalene) at dilute
      concentrations of asphaltenes are presented and discussed. As asphaltenes are
      diluted, it was found that the cluster size decreases and follows a fractal
      scaling law. This observation reveals that asphaltene clusters persist to dilute
      concentrations and maintain fractal characteristics, regardless of concentration.
      For the first time, the fraction of asphaltenes that exist in nanoaggregates
      compared to those molecularly dispersed was estimated from the scattering
      intensity. Significant dissociation was detected at concentrations similar to the
      previously reported critical nanoaggregate concentration (CNAC); however, the
      dissociation was observed to occur gradually as the asphaltene concentration was
      lowered. Complete dissociation was not detected, and aggregates persisted down to
      asphaltene concentrations as low as 15 mg/L (0.00125 vol. %). A simplified
      thermodynamic aggregation model was applied to the measurements, and the free
      energy change of association per asphaltene-asphaltene interaction was calculated
      to be approximately -31 kJ/mol. Finally, novel solvent-corrected WAXS results of
      asphaltene in a liquid environment are presented and reveal three distinct
      separation distances, in contrast to the two separation distances observed in
      diffraction studies of solid phase asphaltenes. Significant differences in the
      WAXS peak positions and shapes between aromatic and nonaromatic solvents suggests
      that there may be large differences between the solvation shell or conformation
      of the asphaltene alkyl shell depending on the surrounding liquid environment. 

PMID- 24279762
TI  - Barriers and facilitators of retention in HIV care and treatment services in
      Iringa, Tanzania: the importance of socioeconomic and sociocultural factors.
AB  - Although an increasing number of people living with HIV (PLHIV) in sub-Saharan
      Africa are benefiting from the rapid scale-up of antiretroviral therapy (ART),
      retention in HIV care and treatment services remains a major concern. We examined
      socioeconomic and sociocultural barriers and potential facilitators of retention
      in ART in Iringa, Tanzania, a region with the second highest prevalence of HIV in
      the country. In 2012, 116 in-depth interviews were conducted to assess community
      members' perceptions, barriers and facilitators of HIV treatment in Iringa,
      including key informants, persons at heightened risk for infection, and HIV
      service-delivery users. Data were transcribed, translated, entered into Atlas.ti,
      coded, and analyzed for key themes. In order to provide the full range of
      perspectives across the community on issues that may affect retention, we report
      findings from all 116 participants, but draw on verbatim quotes to highlight the
      experiences of the 14 PLHIV who reported that they were receiving HIV care and
      treatment services. Despite the growing availability of HIV care and treatment
      services in Iringa, participants reported significant barriers to retention,
      including lack of knowledge and misperceptions of treatment, access problems that
      included difficulties in reaching distant clinics and pervasive poverty that left
      PLHIV unable to cope with out-of-pocket costs associated with their care,
      persistent stigmatization of PLHIV and frequent reliance on alternative healing
      systems instead of biomedical treatment. Positive perceptions of the efficacy of
      ART, improved ART availability in the region, improved access to care through
      supplemental aid, and social support were perceived to enhance treatment
      continuation. Our findings suggest that numerous socioeconomic and sociocultural
      barriers inhibit retention in HIV care and treatment services in this setting.
      Intervention strategies that improve ART accessibility, incorporate supplemental
      aid, enhance social support, reduce stigma, and develop partnerships with
      alternative healers are needed to improve HIV-related outcomes.

PMID- 24279761
TI  - C3 dysregulation due to factor H deficiency is mannan-binding lectin-associated
      serine proteases (MASP)-1 and MASP-3 independent in vivo.
AB  - Uncontrolled activation of the complement alternative pathway is associated with
      complement-mediated renal disease. Factor B and factor D are essential components
      of this pathway, while factor H (FH) is its major regulator. In complete FH
      deficiency, uncontrolled C3 activation through the alternative pathway results in
      plasma C3 depletion and complement-mediated renal disease. These are dependent on
      factor B. Mannan-binding lectin-associated serine proteases 1 and 3 (MASP-1, MASP
      3) have been shown recently to contribute to alternative pathway activation by
      cleaving pro-factor D to its active form, factor D. We studied the contribution
      of MASP-1 and MASP-3 to uncontrolled alternative pathway activation in
      experimental complete FH deficiency. Co-deficiency of FH and MASP-1/MASP-3 did
      not ameliorate either the plasma C3 activation or glomerular C3 accumulation in
      FH-deficient mice. Our data indicate that MASP-1 and MASP-3 are not essential for
      alternative pathway activation in complete FH deficiency. 

PMID- 24279763
TI  - The emergence of blaCTX-M-15-carrying Escherichia coli of ST131 and new sequence
      types in Western China.
AB  - BACKGROUND: blaCTX-M-15, the most widely distributed gene encoding extended
      spectrum beta-lactamases globally, was not common in China. This study was
      performed to characterize blaCTX-M-15-carrying Escherichia coli in western China.
      FINDINGS: Out of 144 Escherichia coli isolates from 20 hospitals in western
      China, 8 were found carrying blaCTX-M-15. blaCTX-M-15 was carried by isolates of
      ST131and 5 new STs (ST3342, ST3513, ST3516, ST3517 and ST3518). The 5 new STs
      shared 5 identical alleles out of 7 but only had up to 2 alleles identical to
      ST131. blaCTX-M-15 was located on plasmids of IncI1 (ST16) or IncFII-related
      group (four replicon types). The co-transfer of a few antimicrobial resistance
      genes including qnrA, qnrB, qnrS, qepA, aac (6')-Ib-cr, aac (3)-II, tetA, blaTEM
      and blaOXA-1 with blaCTX-M-15 were examined but only blaTEM-1 was found co
      transferring with blaCTX-M-15. CONCLUSIONS: Five new STs of E. coli and three new
      types of IncFII-related plasmids carrying blaCTX-M-15 were identified. This study
      together with several reports suggested that blaCTX-M-15 has emerged in China and
      the interruption of both vertical and horizontal transmission of blaCTX-M-15 is
      required to hurdle its further spread.

PMID- 24279767
TI  - An Evidence-based Guideline for the air medical transportation of prehospital
      trauma patients.
AB  - BACKGROUND: Decisions about the transportation of trauma patients by helicopter
      are often not well informed by research assessing the risks, benefits, and costs
      of such transport. OBJECTIVE: The objective of this evidence-based guideline
      (EBG) is to recommend a strategy for the selection of prehospital trauma patients
      who would benefit most from aeromedical transportation. METHODS: A
      multidisciplinary panel was recruited consisting of experts in trauma, EBG
      development, and emergency medical services (EMS) outcomes research.
      Representatives of the Federal Interagency Committee on Emergency Medical
      Services (FICEMS), the National Highway Traffic Safety Administration (NHTSA)
      (funding agency), and the Children's National Medical Center (investigative team)
      also contributed to the process. The panel used the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) methodology to guide question
      formulation, evidence retrieval, appraisal/synthesis, and formulate
      recommendations. The process followed the National Evidence-Based Guideline Model
      Process, which has been approved by the Federal Interagency Committee on EMS and
      the National EMS Advisory Council. RESULTS: Two strong and three weak
      recommendations emerged from the process, all supported only by low or very low
      quality evidence. The panel strongly recommended that the 2011 CDC Guideline for
      the Field Triage of Injured Patients be used as the initial step in the triage
      process, and that ground emergency medical services (GEMS) be used for patients
      not meeting CDC anatomic, physiologic, and situational high-acuity criteria. The
      panel issued a weak recommendation to use helicopter emergency medical services
      (HEMS) for higher-acuity patients if there is a time-savings versus GEMS, or if
      an appropriate hospital is not accessible by GEMS due to systemic/logistical
      factors. The panel strongly recommended that online medical direction should not
      be required for activating HEMS. Special consideration was given to the potential
      need for local adaptation. CONCLUSIONS: Systematic and transparent methodology
      was used to develop an evidence-based guideline for the transportation of
      prehospital trauma patients. The recommendations provide specific guidance
      regarding the activation of GEMS and HEMS for patients of varying acuity. Future
      research is required to strengthen the data and recommendations, define optimal
      approaches for guideline implementation, and determine the impact of
      implementation on safety and outcomes including cost.

PMID- 24279768
TI  - Identifying common and specific microRNAs expressed in peripheral blood
      mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients.
AB  - BACKGROUND: Regardless the regulatory function of microRNAs (miRNA), their
      differential expression pattern has been used to define miRNA signatures and to
      disclose disease biomarkers. To address the question of whether patients
      presenting the different types of diabetes mellitus could be distinguished on the
      basis of their miRNA and mRNA expression profiling, we obtained peripheral blood
      mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6
      gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and
      mRNA microarrays. Data quantification and quality control were obtained using the
      Feature Extraction software, and data distribution was normalized using quantile
      function implemented in the Aroma light package. Differentially expressed
      miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and
      T1DxT2D. Hierarchical clustering was performed using the average linkage
      criterion with Pearson uncentered distance as metrics. RESULTS: The use of the
      same microarrays platform permitted the identification of sets of shared or
      specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR
      126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p,
      hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM,
      and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and
      GDM (19) patients. ROC curves allowed the identification of specific and relevant
      (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR
      1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa
      miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these
      miRNAs targeted mRNAs associated with diabetes pathogenesis. CONCLUSIONS: These
      results indicate that PBMC can be used as reporter cells to characterize the
      miRNA expression profiling disclosed by the different diabetes mellitus
      manifestations. Shared miRNAs may characterize diabetes as a metabolic and
      inflammatory disorder, whereas specific miRNAs may represent biological markers
      for each type of diabetes, deserving further attention.

PMID- 24279769
TI  - Homosecoiridoid alkaloids with amino acid units from the flower buds of Lonicera
      japonica.
AB  - Nine new homosecoiridoid alkaloids, named lonijaposides O-W (1-9), along with 19
      known compounds, were isolated from an aqueous extract of the flower buds of
      Lonicera japonica. Their structures and absolute configurations were determined
      by spectroscopic data analysis and chemical methods. Lonijaposides O-W have
      structural features that involve amino acid units sharing the N atom with a
      pyridinium (1-5) or nicotinic acid (6-9) moiety. The absolute configurations of
      the amino acid units were determined by oxidation of each pyridinium ring moiety
      with potassium ferricyanide, hydrolysis of the oxidation product, and Marfey's
      analysis of the hydrolysate. This procedure was validated by oxidizing and
      hydrolyzing synthetic model compounds. The phenylalanine units in compounds 4, 5,
      and 9 have the d-configuration, and the other amino acid units in 1-3 and 6-8
      possess the l-configuration. Compounds 1, 4, 6, and 9 and the known compounds 3,4
      di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 5'-O-methyladenosine
      exhibited antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2)
      with IC50 values of 3.4-11.6 MUM, and 4 inhibited Coxsackie virus B3 replication
      with an IC50 value of 12.3 MUM. 

PMID- 24279771
TI  - Parietal blood oxygenation level-dependent response evoked by covert visual
      search reflects set-size effect in monkeys.
AB  - Distinguishing a target from distractors during visual search is crucial for goal
      directed behaviour. The more distractors that are presented with the target, the
      larger is the subject's error rate. This observation defines the set-size effect
      in visual search. Neurons in areas related to attention and eye movements, like
      the lateral intraparietal area (LIP) and frontal eye field (FEF), diminish their
      firing rates when the number of distractors increases, in line with the
      behavioural set-size effect. Furthermore, human imaging studies that have tried
      to delineate cortical areas modulating their blood oxygenation level-dependent
      (BOLD) response with set size have yielded contradictory results. In order to
      test whether BOLD imaging of the rhesus monkey cortex yields results consistent
      with the electrophysiological findings and, moreover, to clarify if additional
      other cortical regions beyond the two hitherto implicated are involved in this
      process, we studied monkeys while performing a covert visual search task. When
      varying the number of distractors in the search task, we observed a monotonic
      increase in error rates when search time was kept constant as was expected if
      monkeys resorted to a serial search strategy. Visual search consistently evoked
      robust BOLD activity in the monkey FEF and a region in the intraparietal sulcus
      in its lateral and middle part, probably involving area LIP. Whereas the BOLD
      response in the FEF did not depend on set size, the LIP signal increased in
      parallel with set size. These results demonstrate the virtue of BOLD imaging in
      monkeys when trying to delineate cortical areas underlying a cognitive process
      like visual search. However, they also demonstrate the caution needed when
      inferring neural activity from BOLD activity. 

PMID- 24279772
TI  - Effects of topological defects and diatom vacancies on characteristic vibration
      modes and Raman intensities of zigzag single-walled carbon nanotubes.
AB  - Defects are ubiquitous in carbon nanotubes (CNTs), despite their large formation
      energies, and have astounding effects on their physicochemical properties. In
      this study, we employ density-functional theory (DFT) calculations to study
      systematically the atomic structure, stability, and characteristic vibrations of
      pristine and defected zigzag CNTs, where the defects are of the form of Stone
      Wales (SW) and diatom vacancies (DV). The DFT optimized structures and the phonon
      modes are subsequently used in conjunction with a semiempirical bond-polarization
      model to study the nonresonant Raman spectra. For each defect type, we find two
      CNT structures with defects parallel or oblique to the tube axis. For the SW
      defects, the two structures have similar formation energies, whereas for the DV
      defect, only defects parallel to the tube axis are likely to exist. The results
      show that the defects induce a blue shift in the radial breathing mode (RBM) of
      metallic CNTs, whereas this mode is not shifted for semiconducting CNTs. However,
      the RBM shift or its Raman profile is not sensitive to the defect type. The G
      band showed more sensitivity to the defects in the form of a red/blue shift in
      the frequency, or a partial/complete defragmentation of the G bands. 

PMID- 24279770
TI  - The potential of rice to offer solutions for malnutrition and chronic diseases.
AB  - It is internationally accepted that malnutrition and chronic diseases in
      developing countries are key limitations to achieving the Millennium Development
      Goals. In many developing countries, rice is the primary source of nutrition. In
      those countries, the major forms of malnutrition are Fe-induced anaemia, Zn
      deficiency and Vitamin A deficiency, whereas the major chronic disease challenges
      are Type II diabetes, cardiovascular disease and some cancers. There is a growing
      corpus of evidence regarding both limitations and opportunities as to how rice
      could be an effective vehicle by which to tackle key nutrition and health related
      problems in countries with limited resources. Rice breeding programs are able to
      focus on developing new varieties carrying enhanced amounts of either Fe, Zn or
      beta-carotene because of large public investment, and the intuitive link between
      providing a mineral/vitamin to cure a deficiency in that mineral/vitamin. By
      contrast, there has been little investment in progressing the development of
      particular varieties for potential impact on chronic diseases. In this review
      article we focus on the broad battery of evidence linking rice-related
      nutritional limitations to their impact on a variety of human health issues. We
      discuss how rice might offer sometimes even simple solutions to rectifying key
      problems through targeted biofortification strategies and finally, we draw
      attention to how recent technological (-omics) developments may facilitate untold
      new opportunities for more rapidly generating improved rice varieties
      specifically designed to meet the current and future nutritional needs of a
      rapidly expanding global population. 

PMID- 24279773
TI  - Renal thrombotic microangiopathy in a patient with septic disseminated
      intravascular coagulation.
AB  - BACKGROUND: The mechanism for the development of thrombotic microangiopathy (TMA)
      during sepsis has only been partially elucidated. TMA is recognized as a disease
      caused by various factors, and may be involved in the emergence of organ damage
      in severe sepsis. Here we report a case of TMA that followed disseminated
      intravascular coagulation (DIC) due to severe infection in a patient with a
      reduced ADAMTS-13 activity level. CASE PRESENTATION: An 86-year-old Japanese
      woman was admitted to our hospital because of low back pain and fever. A careful
      evaluation led to a diagnosis of acute obstructive pyelonephritis due to a
      ureteral stone. Proteus mirabilis was isolated from both blood and urine
      cultures. The patient developed systemic inflammatory response syndrome and DIC,
      and was treated with antibiotics and daily continuous hemodiafiltration. Although
      infection and the coagulation abnormalities due to DIC were successfully
      controlled, renal failure persisted and her consciousness level deteriorated
      progressively in association with severe thrombocytopenia and microangiopathic
      hemolytic anemia. We therefore suspected the presence of TMA and started plasma
      exchange, which resulted in an impressive improvement in consciousness as well as
      the laboratory abnormalities. The ADAMTS-13 activity was 44% and the patient
      tested negative for the ADAMTS-13 inhibitor prior to the initiation of plasma
      exchange. A renal biopsy was performed to determine the etiology of acute renal
      injury, which revealed findings that were interpreted to be compatible with the
      sequelae of TMA. The follow-up studies performed after the successful treatment
      of TMA showed that her plasma ADAMTS-13 activity level remained persistently low.
      It is surmised that septic DIC occurring in the presence of preexisting reduced
      ADAMTS-13 activity have led to the development of secondary TMA in the present
      case. CONCLUSION: The present case suggests that TMA can be superimposed on
      sepsis-induced DIC, and plasma exchange is expected to be beneficial in such
      situations. Clinicians should consider the possibility of secondary TMA that
      follows sepsis-induced DIC in certain indicative clinical settings.

PMID- 24279774
TI  - Heterotopic gastric mucosa of the gastrointestinal tract: prevalence,
      histological features, and clinical characteristics.
AB  - BACKGROUND: Heterotopic gastric mucosa (HGM) may be located at sites throughout
      the gastrointestinal (GI) tract. Clinical characteristics of HGM, role of
      Helicobacter pylori infection, natural history, and relationship to neoplastic
      transformation have not sufficiently been explored. AIM: To retrospectively study
      the prevalence, histological features, and clinical characteristics of HGM among
      Chinese patients who underwent upper GI endoscopy. METHODS: Endoscopic,
      histological, and clinical records of patients, who underwent upper GI endoscopy
      (n = 6802) and colonoscopy (n = 3504), respectively, between May 2011 and May
      2012, were collected and retrospectively analyzed. A total of 6716 sex- and age
      matched patients without HGM were enrolled as controls. RESULTS: HGM was
      diagnosed in 86 cases (51 esophageal, 0.75%; 35 duodenal, 0.51%). Male:female
      ratio was 1.4:1 (30/21) for esophageal HGM, 1.7:1 (22/13) for duodenal HGM, and
      1.1:1 (3557/3159) for controls. Two histopathological types of HGM were
      identified: foveolar epithelium alone and foveoloar epithelium together with
      gastric glands. Helicobacter pylori were present in 19.6% of cases with
      esophageal HGM and 20.0% of cases with duodenal HGM. Esophageal HGM was
      significantly associated with dysphagia and globus; duodenal HGM was not
      significantly associated with GI symptoms. Intestinal metaplasia was present in
      two and three patients in both groups, respectively, with no dysplasia or
      carcinoma. CONCLUSION: HGM was present in fewer patients undergoing upper GI
      endoscopy, and it was more often present in men. A careful endoscopic examination
      is required to diagnose HGM, and it should be supported with a biopsy when
      indicated.

PMID- 24279775
TI  - Yellow nail syndrome presenting with postpartum massive pleural effusion.
AB  - Yellow nail syndrome (YNS) is an uncommon clinical syndrome characterized by
      yellow-green discoloration of nails and recurrent respiratory tract lesions,
      pleural effusions and lymphedema. A 38-year-old woman was referred to the
      emergency complaining of chronic cough and increasing dyspnea within last 2
      weeks. She had given birth 1 month ago. On examination, the patient exhibited
      dystrophic yellowish nails and mild peripheral lymphedema. A chest roentgenogram
      revealed a large right pleural effusion and a small left pleural effusion. YNS is
      a rare clinical entity but should be taken into consideration in patients with
      massive pleural effusions and persistent lymphedemas on the postpartum period. 

PMID- 24279776
TI  - Plasmon-enhanced energy transfer for improved upconversion of infrared radiation
      in doped-lanthanide nanocrystals.
AB  - Upconversion of infrared radiation into visible light has been investigated for
      applications in photovoltaics and biological imaging. However, low conversion
      efficiency due to small absorption cross-section for infrared light (Yb(3+)), and
      slow rate of energy transfer (to Er(3+) states) has prevented application of
      upconversion photoluminescence (UPL) for diffuse sunlight or imaging tissue
      samples. Here, we utilize resonant surface plasmon polaritons (SPP) waves to
      enhance UPL in doped-lanthanide nanocrystals. Our analysis indicates that SPP
      waves not only enhance the electromagnetic field, and hence weak Purcell effect,
      but also increase the rate of resonant energy transfer from Yb(3+) to Er(3+) ions
      by 6 fold. While we do observe strong metal mediated quenching (14-fold) of green
      fluorescence on flat metal surfaces, the nanostructured metal is resonant in the
      infrared and hence enhances the nanocrystal UPL. This strong Coulombic effect on
      energy transfer can have important implications for other fluorescent and
      excitonic systems too. 

PMID- 24279777
TI  - Trichoderma harzianum elicits induced resistance in sunflower challenged by
      Rhizoctonia solani.
AB  - AIMS: To investigate the efficacy of Trichoderma harzianum NBRI-1055 (denoted as
      'T-1055') in suppression of seedling blight of sunflower caused by Rhizoctonia
      solani Kuhn and their impact on host defence responses. METHODS AND RESULTS: T
      1055 was applied as seed treatment, soil application and combined application
      (seed treatment + soil application). Higher protection afforded by combined
      application of T-1055 was associated with the marked induction of phenylalanine
      ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (PO) and cinnamyl
      alcohol dehydrogenase (CAD) activities. The activities of PAL and PPO reached
      maximum at 10 days after sowing (DAS), while PO and CAD levels reached maximum at
      12 DAS. This was further supported by the accumulation of total phenolic content
      that showed an increase up to threefold at 14 DAS. In addition, HPLC analysis
      revealed that the contents of ferulic and p-coumaric acids increased by 6.3 and
      4.6 times, respectively, at 14 DAS. Amount of gallic acid was also little more
      than double. Lignin deposition in sunflower root increased by 2.7, 3.4 and 3.7
      times through combined application of T-1055 at 16, 18 and 20 DAS, respectively.
      Combined application also increased the accumulation of PR-2 and PR-3 proteins by
      3.3 and 3.9 times, respectively, at 12 DAS in followed by seed treatment alone.
      CONCLUSIONS: The combined application of T-1055 triggered defence responses in an
      enhanced level in sunflower than the soil and seed alone and provided better
      protection against Rhizoctonia seedling blight. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Rhizospheric fungal bioagent 'T-1055' can enhance protection in sunflower
      against the R. solani pathogen through augmented elicitation of host defence
      responses.

PMID- 24279778
TI  - Multidimensional psychosocial profiles in the elderly and happiness: a cluster
      based identification.
AB  - OBJECTIVES: Evidence supports that subjective well-being (SWB) diminishes in the
      old age and that this decline is strongly determined by elders' psychosocial
      resources. This study explored person-centred, multidimensional, empirically
      derived profiles of psychosocial functioning in the elderly and related each
      trajectory to differing configurations of SWB. METHOD: A community-based,
      convenience sample of Spanish institutionalised and non-institutionalised elders
      voluntarily participated in this cross-sectional study. RESULTS: A cluster
      analysis produced three within-person psychosocial profiles characterised by
      distinct patterns of functioning: highly successful elders demonstrated to be
      healthy, highly confident in their own resources and very active in daily life;
      moderately successful elders demonstrated average functioning across domains,
      although they expected decreases in the future; and highly impaired elders were
      ill and stressed, at a high risk for future health problems and depression, and
      tried to compensate for their status mainly through social support. Each of these
      profiles was related differently to SWB configurations: highly successful elders
      demonstrated significantly higher happiness, positive affect, affect balance and
      life satisfaction; moderately successful elders showed average levels of SWB but
      decreased positive affect; and highly impaired elders demonstrated dramatically
      lower SWB. Furthermore, such trajectories were associated with the elders' living
      condition. The happiest elders were more likely to be home-dwelling elders;
      however, there were fewer unhappy elders among those who were institutionalised.
      CONCLUSION: A person-centred approach to assessing psychosocial and SWB
      configurations provides a rich picture of individual differences in the ageing
      processes and can help in designing interventions aimed at enhancing happiness in
      old age.

PMID- 24279779
TI  - Association of diagnostic delay with impairment severity among institutional care
      facility residents diagnosed with dementia in Ontario, Canada.
AB  - AIM: To compare the levels of cognitive function at the time of diagnosis among
      institutional care facility residents with dementia, who were diagnosed either
      before or after admission to a facility in Ontario, Canada. METHODS: The study
      utilized a population-based secondary data analysis approach, using data from the
      Canadian Institute for Health Information's Continuing Care Reporting System from
      2009 to 2011. Cognitive function within 30 days of diagnosis was measured by a
      seven-point cognitive performance scale (CPS) - 0 (intact) to 6 (very severe
      impairment). RESULTS: Data were extracted from 39633 institutional care facility
      residents who had a diagnosis of dementia on record. The average CPS score was
      higher for residents whose diagnosis was made after admission to a facility than
      for residents whose diagnosis was made before admission (3.1 vs 2.9, P=0.009).
      The proportion of diagnosis at CPS >= 4 (moderately severe to very severe
      impairment) was also higher in the diagnosis after admission group (29.7% vs
      24.6%, P=0.001). Multivariable analysis showed that diagnoses made after
      admission were more likely to be at a severe stage of cognitive decline (CPS >=
      4) than diagnoses made before admission (adjusted odds ratio 1.49, P=0.001). A
      similar result was also noted when comparison was made between mild and moderate
      to-severe stages of cognitive decline. After admission diagnoses were more likely
      to be at moderate-to-severe stages of cognitive decline (CPS >= 3) than before
      admission diagnoses (adjusted odds ratio 1.70, P=0.001). CONCLUSION: Our findings
      suggest that dementia diagnoses after admission to institutional care facilities
      are more likely to be made at poorer stages of cognitive function decline.

PMID- 24279780
TI  - Modification of motivational interviewing for use with people with mild
      intellectual disability and challenging behaviour.
AB  - BACKGROUND: Motivational interviewing is a promising method to increase treatment
      motivation for people with mild intellectual disability and challenging
      behaviour. The purpose of the present study was to identify how professionals
      could adapt motivational interviewing techniques for use with clients. METHOD: We
      conducted semistructured qualitative interviews and focus groups with 26 clients,
      parents, and professionals. A general inductive approach led to the
      identification of multiple core themes. RESULTS: The authors recommend several
      modifications to accommodate motivational interviewing for use with clients:
      adapt to language level, adjust to cognitive abilities, and control for social
      desirability of responding. In addition, certain characteristics of professionals
      were also found to be critical for effective motivational interviewing:
      trustworthiness, engagement, acceptance, empathy, and honesty. CONCLUSIONS:
      Concrete recommendations for the adaptation of the motivational interviewing
      techniques for use with people with mild intellectual disability and challenging
      behaviour are identified. Certain characteristics of professionals are also
      critical for maximising the treatment motivation of clients.

PMID- 24279781
TI  - The Equity Perception Scale - Intellectual Disability Services (EPS-IDS):
      evaluating the reliability and validity of a new measure.
AB  - BACKGROUND: The aim of this paper was to evaluate the reliability and validity of
      the Equity Perception Scale - Intellectual Disability Services (EPS-IDS), a
      detailed measure of staff equity perceptions in services for people with
      intellectual disability (ID). The EPS-IDS contains 3 relationship indices that
      assess staff relationships with their employing organisation, their co-workers,
      and service users. METHOD: Postal questionnaires were used to collect
      quantitative data from a purposive sample of ID service staff. RESULTS: The EPS
      IDS was found to have good internal consistency reliability. The overall test
      retest reliability of the measure, however, was found to be less satisfactory.
      With the exception of the co-worker relationship index, the EPS-IDS indices were
      found to have promising validity. CONCLUSIONS: The findings from the study
      suggest that the EPS-IDS shows some promise as a measure of the equity
      perceptions of ID service staff. Further refinements to the relationship indices,
      however, may be required.

PMID- 24279782
TI  - Reliability of an assessment used in formal accommodation services: implications
      for adults with an intellectual disability.
AB  - BACKGROUND: The Revised Irrabeena Core Skills Assessment (RICSA) is used in
      formal accommodation services and evaluates the functional skills of adults with
      an intellectual disability. The assessment is used to inform training for skills
      development. This study focused on establishing evidence for interrater
      reliability of the RICSA. METHOD: The RICSA was completed by 101 staff members on
      30 adults living in group homes. Interviews were conducted with 9 staff members
      in order to identify potential issues that may affect the reliability of the
      assessment. Interrater reliability was analysed using the intraclass correlation
      coefficient (ICC), and thematic analysis was conducted from the interview data.
      RESULTS: The ICC values ranged from .63 to .73 across the 5 main domains of the
      RICSA. CONCLUSIONS: The agreement found may be regarded as unsatisfactory given
      that the use of the RICSA is to inform skills training for people with an
      intellectual disability.

PMID- 24279783
TI  - Vocabulary development in children with Down syndrome: longitudinal and cross
      sectional data.
AB  - BACKGROUND: Research findings on vocabulary development (1) in children with Down
      syndrome are inconsistent. This study aimed to analyse the developmental trend of
      vocabulary growth in children with Down syndrome and the relationships between
      vocabulary and chronological and developmental age. METHOD: Children's vocabulary
      size was assessed by a parental report (the Italian version of the MacArthur
      Bates Communicative Development Inventories [CDI]). A longitudinal study,
      involving 18 children with Down syndrome, and a cross-sectional study, involving
      27 children with Down syndrome, were conducted. RESULTS: The variability in
      children's vocabulary size increased from a chronological age of 36 months. Both
      vocabulary size (from 36 months) and developmental level (from 42 months) were
      significant predictors of lexical outcomes at 48 months. A comparison with
      normative data showed that children with Down syndrome had a significantly lower
      vocabulary size than typically developing children at the same developmental age.
      CONCLUSION: Although there are similarities with vocabulary growth in typically
      developing children, lexical development in children with Down syndrome appears
      to lag behind their cognitive development.

PMID- 24279784
TI  - Reliability of a method for establishing the capacity of individuals with an
      intellectual disability to respond to Likert scales.
AB  - BACKGROUND: The study reported here was an examination of the reliability of a
      method for determining acquiescent responding and the capacity to respond to
      items using a Likert scale response format by adults with an intellectual
      disability. METHOD: Reliability of the outcomes of these procedures was
      investigated using a test-retest design. Associations with receptive vocabulary
      were examined. RESULTS: The majority of the participants did not demonstrate
      acquiescent responding. Individuals' responses to the Likert-type discrimination
      tasks were consistent, although this varied somewhat depending upon the
      abstractness of the task. There was some association between receptive language
      age equivalence scores and respondent performance. CONCLUSION: It is recommended
      that the pretest protocol (a) be modified to improve its reliability, and (b)
      this modified version be used with study participants who have an intellectual
      disability to ascertain the appropriate level of choice to be used for items that
      use a Likert response format.

PMID- 24279785
TI  - Alcohol and its relationship to offence variables in a cohort of offenders with
      intellectual disability.
AB  - BACKGROUND: Alcohol use and misuse may be lower in people with intellectual
      disability (ID) than in the general population but may be related to offending.
      METHOD: Alcohol-related crime and history of alcohol use was recorded in 477
      participants with ID referred to forensic ID services and related to offending.
      RESULTS: Level of alcohol-related crime and history of alcohol misuse was lower
      than in some previous studies at 5.9% and 20.8%, respectively. History of alcohol
      abuse was associated with alcohol-related offences and theft. Higher rates of
      alcohol problem history were associated with histories of a number of offences,
      psychiatric disturbance in adulthood, psychiatric disturbance in childhood, and
      experiences of childhood adversity. Most effect sizes were weak or moderate.
      CONCLUSIONS: The convergence of childhood adversity, psychiatric problems in
      childhood and adulthood, and alcohol abuse is consistent with studies that have
      found these as risk markers for offending.

PMID- 24279786
TI  - Emotion recognition by children with Down syndrome: a longitudinal study.
AB  - BACKGROUND: According to the literature, children with Down syndrome (DS) have
      difficulties recognising facial expressions. Yet abilities to recognise emotional
      expressions are often assessed in tasks that imply comprehension of words for
      emotions. We investigated the development of these abilities in children with DS
      in a longitudinal study that did not involve lexical knowledge of emotions.
      METHOD: Children with DS and nonspecific intellectual disability and typically
      developing children matched for developmental age (DA) were assessed once a year
      over 3 years. They were asked to recognise the facial expression of an emotion
      after hearing a vocalisation. RESULTS: In each annual session, children with DS
      were not significantly different from others at recognising emotions. Their
      abilities to discriminate basic emotions improved significantly and to a similar
      extent to those of other children. CONCLUSION: The findings indicate that
      children with DS develop emotion recognition abilities similarly to other
      children of the same DA.

PMID- 24279787
TI  - Mentors' experiences of using the Active Mentoring model to support older adults
      with intellectual disability to participate in community groups.
AB  - BACKGROUND: Social inclusion is a widely acknowledged goal; who is best
      positioned to provide support and how support is delivered are key questions.
      Using Active Mentoring training, members of community groups mentored a person
      with intellectual disability and supported their inclusion in that group.
      METHODS: Interviews with 14 mentors explored their experiences of supporting a
      previously unknown person with intellectual disability to participate in their
      community group. FINDINGS: The core theme was No Different From Us. Mentors saw
      beyond the disability, they valued others, were community leaders, and had
      intrinsic qualities. With some basic orientation to the task, mentors were able
      to support the inclusion of their mentee in the group. CONCLUSION: Community
      members are willing to support people with intellectual disability to join their
      community groups. The Active Mentoring training is one way of harnessing the
      goodwill of community groups and their members to include people with
      intellectual disability to participate on an individual basis in community
      groups.

PMID- 24279788
TI  - Evaluating staff training: taking account of interactions between staff and
      clients with intellectual disability and challenging behaviour.
AB  - BACKGROUND: Hastings (2010) has recently emphasised 3 aspects in the training of
      staff who serve clients with mild to moderate intellectual disability and
      challenging behaviour (CB): Staff attitudes, self-awareness, and clients'
      perspectives. This study investigates whether programs include these aspects.
      METHOD: A systematic search yielded 11 relevant articles. RESULTS: Generally, all
      programs aimed to improve staff knowledge and skills. Client variables concerned
      frequencies and severities of CB. None of the studies included clients'
      perspectives or staff attitudes and self-awareness. CONCLUSIONS: The fact that
      staff attitudes and awareness or clients' perspectives were not among the main
      goals of the training studies suggests that recent views of effective treatment
      of CB are not yet the object of scientific study. Given the acknowledgment of
      these aspects, it is warranted that future research focuses upon these recent
      insights.

PMID- 24279792
TI  - Nucleotide oligomerization domain 1 ligation suppressed murine allergen-specific
      T-cell proliferation and airway hyperresponsiveness.
AB  - The cytosolic nucleotide oligomerization domain (NOD)-like receptors NOD1 and
      NOD2 are important contributors to the intracellular recognition of pathogens
      including Chlamydophila pneumoniae, but little is known about their influence on
      allergen-induced airway inflammation. In BALB/c mice, we observed that infection
      with C. pneumoniae before systemic sensitization with ovalbumin (OVA) and local
      OVA airway exposure diminished airway hyperresponsiveness (AHR). Thus, the impact
      of the NOD1 agonist FK156 and the NOD2 agonist muramyl dipeptide given 6 hours
      before each sensitization or airway challenge was evaluated regarding AHR, OVA
      specific plasma immunoglobulins, bronchoalveolar lavage fluid differentials, and
      cytokines. Spleen dendritic cells of FK156-treated mice were isolated and
      cocultured with OVA-specific T cells isolated from DO11.10 mice, and T-cell
      proliferation was quantified after OVA restimulation. T-cell proliferation was
      investigated in vivo in lungs and lymph nodes of FK156-treated and OVA-exposed
      DO11.10 mice. FK156, but not muramyl dipeptide, reduced AHR and pulmonary
      eosinophilic infiltration if given before OVA sensitization or challenge, whereas
      T-helper (Th)2 cytokines were not diminished. Dendritic cells from FK156-treated
      mice evoked less OVA-specific T-cell proliferation as compared with solvent
      treated controls. Similarly, antigen-specific T-cell activation in lung tissue
      was diminished after FK156 treatment. We conclude that NOD1 activation reduced
      AHR in allergen-induced lung inflammation, which was accompanied by a reduction
      of allergen-specific T-cell proliferation.

PMID- 24279793
TI  - Loss of MEF2D expression inhibits differentiation and contributes to oncogenesis
      in rhabdomyosarcoma cells.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is a highly malignant pediatric cancer that is
      the most common form of soft tissue tumors in children. RMS cells have many
      features of skeletal muscle cells, yet do not differentiate. Thus, our studies
      have focused on the defects present in these cells that block myogenesis.
      METHODS: Protein and RNA analysis identified the loss of MEF2D in RMS cells.
      MEF2D was expressed in RD and RH30 cells by transient transfection and selection
      of stable cell lines, respectively, to demonstrate the rescue of muscle
      differentiation observed. A combination of techniques such as proliferation
      assays, scratch assays and soft agar assays were used with RH30 cells expressing
      MEF2D to demonstrate the loss of oncogenic growth in vitro and xenograft assays
      were used to confirm the loss of tumor growth in vivo. RESULTS: Here, we show
      that one member of the MEF2 family of proteins required for normal myogenesis,
      MEF2D, is largely absent in RMS cell lines representing both major subtypes of
      RMS as well as primary cells derived from an embryonal RMS model. We show that
      the down regulation of MEF2D is a major cause for the failure of RMS cells to
      differentiate. We find that MyoD and myogenin are bound with their dimerization
      partner, the E proteins, to the promoters of muscle specific genes in RMS cells.
      However, we cannot detect MEF2D binding at any promoter tested. We find that
      exogenous MEF2D expression can activate muscle specific luciferase constructs, up
      regulate p21 expression and increase muscle specific gene expression including
      the expression of myosin heavy chain, a marker for skeletal muscle
      differentiation. Restoring expression of MEF2D also inhibits proliferation, cell
      motility and anchorage independent growth in vitro. We have confirmed the
      inhibition of tumorigenicity by MEF2D in a tumor xenograft model, with a complete
      regression of tumor growth. CONCLUSIONS: Our data indicate that the oncogenic
      properties of RMS cells can be partially attributed to the loss of MEF2D
      expression and that restoration of MEF2D may represent a useful therapeutic
      strategy to decrease tumorigenicity.

PMID- 24279794
TI  - A superoxide dismutase purified from the roots from Stemona tuberosa.
AB  - Proteins from the fresh roots of Stemona tuberosa (Stemonaceae) were extracted
      into 20 mM phosphate buffer, pH 7.2/0.1 M NaCl, precipitated with 90% saturation
      ammonium sulfate, and enriched by diethylaminoethanol (DEAE) cellulose. The
      protein eluted as a single main peak from the unbound fractions (ST-1), and
      appeared as a single band with superoxide dismutase (SOD) activity after native
      polyacrylamide gel electrophoresis (PAGE) resolution and zymogram development. ST
      1 was classified as SOD due to its strong inhibition by HCN and H2O2. The amino
      acid sequence of three tryptic peptides of ST-1 matched with the SOD isozymes
      from Ananas comosus and Solanum lycopersicum. The SOD consisted of at least two
      heterologous protein subunits with molecular mass of 17.6 and 31.5 kD,
      respectively, and had an optimal SOD activity at pH 5 and over a temperature
      range of 0-50 degrees C. MgCl2, MnCl2, and HgCl2 were strongly inhibitory at all
      concentrations tested. The SOD activity was completely negated in the presence of
      0.5 mM SDS or 5 mM HgCl2. The relationship between riboflavin and nitroblue
      tetrazolium (NBT) on SOD activity was linear, giving K m and V max values of the
      purified SOD of 62.414 +/- 0.015 M and 101.010 +/- 0.022 umol/min/mg protein for
      NBT and 27.389 +/- 0.032 M and 38.167 +/- 0.021 umol/min/mg protein for
      riboflavin, respectively.

PMID- 24279795
TI  - Anolis sex chromosomes are derived from a single ancestral pair.
AB  - To explain the frequency and distribution of heteromorphic sex chromosomes in the
      lizard genus Anolis, we compared the relative roles of sex chromosome
      conservation versus turnover of sex-determining mechanisms. We used model-based
      comparative methods to reconstruct karyotype evolution and the presence of
      heteromorphic sex chromosomes onto a newly generated Anolis phylogeny. We found
      that heteromorphic sex chromosomes evolved multiple times in the genus.
      Fluorescent in situ hybridization (FISH) of repetitive DNA showed variable rates
      of Y chromosome degeneration among Anolis species and identified previously
      undetected, homomorphic sex chromosomes in two species. We confirmed homology of
      sex chromosomes in the genus by performing FISH of an X-linked bacterial
      artificial chromosome (BAC) and quantitative PCR of X-linked genes in multiple
      Anolis species sampled across the phylogeny. Taken together, these results are
      consistent with long-term conservation of sex chromosomes in the group. Our
      results pave the way to address additional questions related to Anolis sex
      chromosome evolution and describe a conceptual framework that can be used to
      evaluate the origins and evolution of heteromorphic sex chromosomes in other
      clades. 

PMID- 24279797
TI  - Tailoring molecular self-assembly of magnetic phthalocyanine molecules on Fe- and
      Co-intercalated graphene.
AB  - We investigate molecule-molecule, as well as molecule-substrate, interactions of
      phthalocyanine molecules deposited on graphene. In particular, we show how to
      tune the self-assembly of molecular lattices in two dimensions by intercalation
      of transition metals between graphene and Ir(111): modifying the surface
      potential of the graphene layer via intercalation leads to the formation of
      square, honeycomb, or Kagome lattices. Finally, we demonstrate that such surface
      induced molecular lattices are stable even at room temperature. 

PMID- 24279796
TI  - Impaired noradrenaline homeostasis in rats with painful diabetic neuropathy as a
      target of duloxetine analgesia.
AB  - BACKGROUND: Painful diabetic neuropathy (PDN) is a serious complication of
      diabetes mellitus that affects a large number of patients in many countries. The
      molecular mechanisms underlying the exaggerated nociception in PDN have not been
      established. Recently, duloxetine (DLX), a serotonin and noradrenaline re-uptake
      inhibitor, has been recommended as one of the first-line treatments of PDN in the
      United States Food and Drug Administration, the European Medicines Agency and the
      Japanese Guideline for the Pharmacologic Management of Neuropathic pain. Because
      selective serotonin re-uptake inhibitors show limited analgesic effects in PDN,
      we examined whether the potent analgesic effect of DLX contributes toward
      improving the pathologically aberrant noradrenaline homeostasis in diabetic
      models. RESULTS: In streptozotocin (STZ) (50 mg/kg, i.v.)-induced diabetic rats
      that exhibited robust mechanical allodynia and thermal hyperalgesia, DLX (10
      mg/kg, i.p.) significantly and markedly increased the nociceptive threshold. The
      analgesic effect of DLX was nullified by the prior administration of N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) (50 mg/kg, i.p.), which
      drastically eliminated dopamine-beta-hydroxylase- and norepinephrine transporter
      immunopositive fibers in the lumbar spinal dorsal horn and significantly reduced
      the noradrenaline content in the lumbar spinal cord. The treatment with DSP-4
      alone markedly lowered the nociceptive threshold in vehicle-treated non-diabetic
      rats; however, this pro-nociceptive effect was occluded in STZ-treated diabetic
      rats. Furthermore, STZ-treated rats exhibited a higher amount of dopamine-beta
      hydroxylase- and norepinephrine transporter-immunopositive fibers in the dorsal
      horn and noradrenaline content in the spinal cord compared to vehicle-treated
      rats. CONCLUSIONS: Impaired noradrenaline-mediated regulation of the spinal
      nociceptive network might underlie exaggerated nociception in PDN. DLX might
      exert its analgesic effect by selective enhancement of noradrenergic signals,
      thus counteracting this situation.

PMID- 24279801
TI  - Efficacy and safety of vildagliptin in new-onset diabetes after kidney
      transplantation--a randomized, double-blind, placebo-controlled trial.
AB  - New-onset diabetes after transplantation (NODAT) is a serious complication after
      kidney transplantation, but therapeutic strategies remain underexplored.
      Dipeptidyl peptidase-4 (DPP-4) inhibitors selectively foster insulin secretion
      without inducing hypoglycemia, which might be advantageous in kidney transplant
      recipients (KTRs) with NODAT. We conducted a randomized, double-blind, placebo
      controlled, phase II trial to assess safety and efficacy of the DPP-4 inhibitor
      vildagliptin. Intraindividual differences in oral glucose tolerance test (OGTT)
      derived 2-h plasma glucose (2HPG) from baseline to 3 months after treatment
      served as primary endpoint. Among secondary outcomes, we evaluated HbA1c,
      metabolic and safety parameters, as well as OGTTs at 1 month after drug
      discontinuation. Of 509 stable KTRs who were screened in our outpatient clinic,
      63 (12.4%) had 2HPG >= 200 mg/dL, 33 of them were randomized and 32 completed the
      study. In the vildagliptin group 2HPG and HbA1c were profoundly reduced in
      comparison to placebo (vildagliptin: 2HPG = 182.7 mg/dL, HbA1c = 6.1%; placebo:
      2HPG = 231.2 mg/dL, HbA1c = 6.5%; both p <= 0.05), and statistical significance
      was achieved for the primary endpoint (vildagliptin: 2HPG-difference -73.7 +/-
      51.3 mg/dL; placebo: -5.7 +/- 41.4 mg/dL; p < 0.01). Adverse events were
      generally mild and occurred at similar rates in both groups. In conclusion, DPP-4
      inhibition in KTRs with overt NODAT was safe and efficient, providing a novel
      treatment alternative for this specific form of diabetes.

PMID- 24279802
TI  - Stereotactic Body radiation therapy for liver tumors with or without rotational
      intensity modulated radiation therapy.
AB  - BACKGROUND: To evaluate the feasibility and efficacy of Stereotactic body
      radiation therapy (SBRT) for primary liver lesions and liver metastases treated
      with linear accelerators with or without rotational Intensity Modulated
      RadioTherapy (IMRT). METHODS: Patients with either hepatocellular carcinoma,
      cholangiocarcinoma or metastatic liver lesions who had one to three lesions
      treated with SBRT in a single institution were retrospectively reviewed. Tumor
      response was evaluated according to EASL criteria 3 months after SBRT completion
      using MRI and/or abdominal CT scan. Responses were categorised as: Stable Disease
      (SD), Partial Response (PR), Complete Response (CR), Local Progression or Distant
      Progression in cases of new intra-hepatic lesions out-of-field or extra-hepatic
      metastases. Local Control (LC), Progression Free Survival (PFS), Overall Survival
      (OS) and treatment-related toxicities are reported. RESULTS: Between 2007 and
      2012, 20 patients with a total of 24 lesions were treated with SBRT. Fourteen
      patients presented hepatocellular carcinoma (HCC), the others had either
      metastatic lesions from colorectal cancer (CRC) or cholangiocarcinoma. The median
      diameter of the lesions was 23 mm (5-98).The dose per fraction ranged from 6 to
      20 Gy with a median total dose of 60 Gy (range: 36-60 Gy). The dose was
      prescribed to the 80% isodose line covering the PTV.The median follow-up was 24
      months (15.7-29.7).The actuarial LC rate was 78% for patients with HCC and 83%
      for those with adenocarcinoma and cholangiocarcinoma. Median OS was 37 months and
      OS rates were 83% at 12 and 24 months for HCC and 100% for adenocarcinoma. PFS
      was 54% for HCC and 50% for other types of tumors at 24 months.Acute grade 3-4
      toxicities occurred in 2 patients; a small proportion of the other patients
      experienced grade 1 or 2 toxicities. CONCLUSIONS: SBRT provides excellent local
      control with minimal side effects in selected patients.

PMID- 24279803
TI  - Effect of long-chain triglyceride lipid emulsion on bupivacaine-induced changes
      in electrophysiological parameters of rabbit Purkinje cells.
AB  - Lipid emulsions are used in the reversal of local anesthetic toxicity. The aim of
      this study was to investigate the cellular electrophysiological effects of long
      chain triglyceride lipid emulsion (LCTE) on cardiac action potential
      characteristics and conduction disturbances induced by bupivacaine. Purkinje
      fibers were dissected from the left ventricle of New Zealand white rabbit hearts
      and superfused with either Tyrode's solution during 30 min (control group), with
      bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M alone, or in the presence of LCTE
      0.5%, in addition, LCTE at 0.1%, 0.5%, and 1% was perfused alone.
      Electrophysiological parameters were recorded using the conventional
      microelectrode technique (37  degrees C, 1 Hz frequency). Bupivacaine 5.10(-5) M
      induced conduction blocks (8/8 preparations): LCTE 0.5% suppressed the
      bupivacaine 5.10(-5) M-induced conduction blocks (1/8 preparations). Exposure to
      bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M resulted in a significant decrease
      in the maximal rate of depolarization (Vmax) (respectively, 25%, 55%, 75%; P <
      0.002 vs. control group). In the presence of LCTE 0.5%, bupivacaine 10(-6) M did
      not significantly decreased Vmax (13%; P = 0.10 vs. control group). The decrease
      in Vmax resulting from bupivacaine 10(-5) M alone was significantly less in the
      presence of LCTE 0.5% (P < 0.01 vs. bupivacaine 10(-5) M alone). Exposure to
      bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M alone or in the presence of LCTE
      0.5% resulted in a significant decrease in action potential duration measured at
      50% and 90% repolarization (APD50 and APD90; P < 0.01 vs. control group). LCTE
      inhibited the Purkinje fibers conduction blocks induced by bupivacaine. Moreover,
      LCTE 0.5% attenuates the decrease in Vmax induced by bupivacaine 10(-6) M and 10(
      5) M.

PMID- 24279805
TI  - Multipolar interference for directed light emission.
AB  - By directing light, optical antennas can enhance light-matter interaction and
      improve the efficiency of nanophotonic devices. Here we exploit the interference
      among the electric dipole, quadrupole, and magnetic dipole moments of a split
      ring resonator to experimentally realize a compact directional optical antenna.
      This single-element antenna design robustly directs emission even when covered
      with nanometric emitters at random positions, outperforming previously
      demonstrated nanoantennas with a bandwidth of 200 nm and a directivity of 10.1 dB
      from a subwavelength structure. The advantages of this approach bring directional
      optical antennas closer to practical applications. 

PMID- 24279804
TI  - Reply to "comment on 'prebiotic chemistry within a simple impacting icy
      mixture'".

PMID- 24279806
TI  - Nonanthocyanin secondary metabolites of black raspberry (Rubus occidentalis L.)
      fruits: identification by HPLC-DAD, NMR, HPLC-ESI-MS, and ESI-MS/MS analyses.
AB  - Nonanthocyanin secondary metabolites potentially contributing to the
      antiproliferative bioactivity of black raspberry ( Rubus occidentalis L.) fruits
      were extracted in ethyl acetate and isolated by semipreparative and analytical
      HPLC and analyzed by NMR, HPLC-ESI-MS, and ESI-MS/MS techniques. Here we present
      complete and partial structures of a variety of the chemical entities such as
      quercetin 3-glucoside, quercetin 3-rutinoside, myricetin glucoside,
      dihydrokaempferol glucoside, benzoic acid beta-d-glucopyranosyl ester, 3,4
      dihydroxybenzoic acid, epicatechin, caffeic acid, p-coumaric acid, p-coumaryl
      glucoside, p-coumaryl sugar ester, ellagic acid, methyl ellagic acid
      acetylpentose, methyl ellagic acid valerylpentose, trans-piceid, phloretin
      glucoside (phloridzin), dihydrosinapic acid, salicylic acid beta-d-glucopyranosyl
      ester, a salicylic acid derivative without attached sugar, p-alkylphenyl
      glucoside, and a citric acid derivative. To our knowledge, 15 of these compounds
      were not previously reported in black raspberry fruits. 

PMID- 24279807
TI  - Photosensitized damage inflicted on plasma membranes of live cells by an
      extracellular generator of singlet oxygen--a linear dependence of a lethal dose
      on light intensity.
AB  - We describe a study of the influence of a dose rate, i.e. light intensity or
      photon flux, on the efficiency of induction of a loss of integrity of plasma
      membranes of live cells in culture. The influence of a photon flux on the size of
      the light dose, which was capable of causing lethal effects, was measured in an
      experimental system where singlet oxygen was generated exclusively outside of
      live cells by ruthenium(II) phenantroline complex. Instantaneous, sensitive
      detection of a loss of integrity of a plasma membrane was achieved by
      fluorescence confocal imaging of the entry of this complex into a cell interior.
      We demonstrate that the size of the lethal dose of light is directly proportional
      to the intensity of the exciting light. Thus, the probability of a photon of the
      exciting light inflicting photosensitized damage on plasma membranes diminishes
      with increasing density of the incident photons. 

PMID- 24279808
TI  - Noninvasive positive pressure ventilation is required following extubation at the
      pulmonary infection control window: a prospective observational study.
AB  - INTRODUCTION: Timely extubation and sequential invasive to noninvasive positive
      pressure ventilation (NPPV) at the pulmonary infection control (PIC) window is
      beneficial for patients with acute exacerbation of chronic obstructive pulmonary
      disease (AECOPD). However, it remains unclear whether patients can breathe
      independently at the PIC window and if NPPV is indeed necessary after extubation.
      OBJECTIVES: To assess whether AECOPD patients can breathe independently at the
      PIC window and thus whether NPPV is necessary after extubation. METHODS: We
      performed a prospective observational study at a university hospital during a 9
      month period. We used the spontaneous breathing trial (SBT) to assess whether
      each patient could breathe independently at the PIC window, then performed
      extubation. Patients who passed the SBT received venturi oxygen therapy only,
      whereas those that failed received NPPV. However, if the former showed
      respiratory distress, they too received NPPV. The primary outcome variables were
      SBT pass/fail, the demand for NPPV and rate of reintubation within 72 h following
      extubation. RESULTS: In all, 23 patients were enrolled, 15 (65%) of which passed
      the SBT. Of these, 12 (80%) developed respiratory distress after extubation and
      required NPPV (one of whom required reintubation). Of the eight patients that
      failed, one received reintubation after NPPV. The reintubation rates within 72 h
      following extubation of SBT-pass (7%) and SBT-fail (13%) patients were
      comparable. CONCLUSION: Our results provide experimental evidence that most
      AECOPD patients can breathe independently at the PIC window, but nonetheless
      develop respiratory distress and thus require NPPV following extubation.

PMID- 24279809
TI  - The Rice Oligonucleotide Array Database: an atlas of rice gene expression.
AB  - BACKGROUND: Microarray technologies facilitate high-throughput gene expression
      analysis. However, the diversity of platforms for rice gene expression analysis
      hinders efficient analysis. Tools to broadly integrate microarray data from
      different platforms are needed. RESULTS: In this study, we developed the Rice
      Oligonucleotide Array Database (ROAD, http://www.ricearray.org) to explore gene
      expression across 1,867 publicly available rice microarray hybridizations. The
      ROAD's user-friendly web interface and variety of visualization tools facilitate
      the extraction of gene expression profiles using gene and microarray element
      identifications. The ROAD supports meta-analysis of genes expressed in different
      tissues and at developmental stages. Co-expression analysis tool provides
      information on co-regulation between genes under general, abiotic and biotic
      stress conditions. Additionally, functional analysis tools, such as Gene Ontology
      and KEGG (Kyoto Encyclopedia of Genes and Genomes) Orthology, are embedded in the
      ROAD. These tools facilitate the identification of meaningful biological patterns
      in a list of query genes. CONCLUSIONS: The Rice Oligonucleotide Array Database
      provides comprehensive gene expression profiles for all rice genes, and will be a
      useful resource for researchers of rice and other grass species.

PMID- 24279810
TI  - Spatial epidemiology of Escherichia coli O157:H7 in dairy cattle in relation to
      night roosts Of Sturnus vulgaris (European Starling) in Ohio, USA (2007-2009).
AB  - The goal of our study was to use spatial scan statics to determine whether the
      night roosts of European starlings (Sturnus vulgaris) act as point sources for
      the dissemination of Escherichia coli O157:H7 among dairy farms. From 2007 to
      2009, we collected bovine faecal samples (n = 9000) and starling gastrointestinal
      contents (n = 430) from 150 dairy farms in northeastern Ohio, USA. Isolates of E.
      coli O157:H7 recovered from these samples were subtyped using multilocus variable
      number tandem repeat analysis (MLVA). Generated MLVA types were used to construct
      a dendrogram based on a categorical multistate coefficient and unweighted pair
      group method with arithmetic mean (UPGMA). Using a focused spatial scan
      statistic, we identified statistically significant spatial clusters among dairy
      farms surrounding starling night roosts, with an increased prevalence of E. coli
      O157:H7-positive bovine faecal pats, increased diversity of distinguishable MLVA
      types and a greater number of isolates with MLVA types from bovine-starling
      clades versus bovine-only clades. Thus, our findings are compatible with the
      hypothesis that starlings have a role in the dissemination of E. coli O157:H7
      among dairy farms, and further research into starling management is warranted.

PMID- 24279811
TI  - Selection of colon cancer patients for neoadjuvant chemotherapy by preoperative
      CT scan.
AB  - OBJECTIVE: Preoperative staging is essential to plan correct treatment of colon
      cancer and calls for objective, accurate methods for the introduction of
      neoadjuvant chemotherapy, which represents a new treatment option. PURPOSE: To
      evaluate the diagnostic accuracy of multislice computed tomography (CT) in local
      staging of colon cancer correlated with histopathological parameters, including
      criteria for adjuvant chemotherapy. MATERIAL AND METHODS: A total of 74 included
      patients had preoperative CT scans and surgical resection of their colon tumors.
      Tumor stage (T-stage), extramural tumor invasion (ETI), nodal stage (N-stage),
      extramural venous invasion (EVI) and the distance from tumor to nearest
      retroperitoneal fascia (DRF) were retrospectively assessed on the CT scan and
      compared blindly with the results of the pathological examination, including
      evaluation of the criteria for adjuvant chemotherapy. Advanced tumors were
      defined as T3 with ETI >=5 mm or T4. RESULTS: Sixty-nine percent of the tumors
      were correctly T-staged by CT, 7% were overstaged and 24% were understaged. As to
      correct recognition of ETI on the CT scan, the observer was 73% accurate compared
      with histology (70% sensitivity (95% CI: 53-82%), 78% specificity (95% CI: 60
      90%), 81% positive predictive value (PPV) (95% CI: 63-91%) and 66% negative
      predictive value (NPV) (95% CI: 49-80%). N-stage, EVI and DRF had poor accuracy:
      53%, 53% and 64%. All patients with advanced tumors on CT fulfilled the criteria
      for adjuvant chemotherapy. Positive predictive value: 100% (95% CI: 88-100%).
      CONCLUSION: CT has a potential in the preoperative selection of advanced tumors
      suitable for neoadjuvant chemotherapy without overtreatment of low-risk patients.

PMID- 24279812
TI  - Sex differences in mortality of admitted patients with personality disorders in
      North Norway--a prospective register study.
AB  - BACKGROUND: It is well established that patients with serious mental disorders
      have higher mortality than the general population, yet there are few studies on
      mortality of both natural and unnatural causes in patients with personality
      disorders. The aim of this study was to investigate the mortality of in-patients
      with personality disorder diagnosis in a 27-year follow-up cohort in North
      Norway, with a special focus on gender differences. METHOD: Based on a hospital
      case register covering 1980 to 2006, 284 female and 289 male patients were
      included. The cohort was linked to the Norwegian Cause of Death Registry for
      information concerning mortality. The mortality rates were adjusted for age by
      applying a Poisson regression model. The relative mortality in men compared to
      women was tested with Cox regression with attained age as the time variable. The
      number of deaths to be expected among the patients if the mortality rates of the
      general population in Norway had prevailed was estimated and excess mortality,
      expressed by the standardized mortality ratio (SMR), calculated. RESULTS: When
      compared to the mortality in the general population, men and women with
      personality disorder diagnoses had 4.3 (95% CI: 3.2-5.9) and 2.9 (95% CI: 1.9
      4.5) times, respectively, increased total mortality. Patients with personality
      disorder diagnoses have particularly high mortality for unnatural deaths; 9.7
      (95% confidence interval (CI): 6.3-15.1) times higher for men and 17.8 (95% CI:
      10.1-30.3) for women, respectively, and even higher for suicides--15 (95% CI: 9
      27) for men and 38 (95% CI: 20-70) for women. The mortality due to natural causes
      was not statistically significantly increased in women, whereas men had 2.8 (95%
      CI: 1.8-4.4) times higher mortality of natural deaths than the general
      population. CONCLUSION: Compared to the general population, patients with a
      personality disorder have high mortality, particularly mortality from unnatural
      causes. The number of deaths caused by suicides is especially high for women. Men
      also have higher mortality of natural causes than the general population.

PMID- 24279813
TI  - An Evidence-based Guideline for prehospital analgesia in trauma.
AB  - BACKGROUND: The management of acute traumatic pain is a crucial component of
      prehospital care and yet the assessment and administration of analgesia is highly
      variable, frequently suboptimal, and often determined by consensus-based regional
      protocols. OBJECTIVE: To develop an evidence-based guideline (EBG) for the
      clinical management of acute traumatic pain in adults and children by advanced
      life support (ALS) providers in the prehospital setting. Methods. We recruited a
      multi-stakeholder panel with expertise in acute pain management, guideline
      development, health informatics, and emergency medical services (EMS) outcomes
      research. Representatives of the National Highway Traffic Safety Administration
      (sponsoring agency) and a major children's research center (investigative team)
      also contributed to the process. The panel used the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) methodology to guide the process
      of question formulation, evidence retrieval, appraisal/synthesis, and formulation
      of recommendations. The process also adhered to the National Prehospital Evidence
      Based Guideline (EBG) model process approved by the Federal Interagency Council
      for EMS and the National EMS Advisory Council. RESULTS: Four strong and three
      weak recommendations emerged from the process; two of the strong recommendations
      were linked to high- and moderate-quality evidence, respectively. The panel
      recommended that all patients be considered candidates for analgesia, regardless
      of transport interval, and that opioid medications should be considered for
      patients in moderate to severe pain. The panel also recommended that all patients
      should be reassessed at frequent intervals using a standardized pain scale and
      that patients should be re-dosed if pain persists. The panel suggested the use of
      specific age-appropriate pain scales. CONCLUSION: GRADE methodology was used to
      develop an evidence-based guideline for prehospital analgesia in trauma. The
      panel issued four strong recommendations regarding patient assessment and
      narcotic medication dosing. Future research should define optimal approaches for
      implementation of the guideline as well as the impact of the protocol on safety
      and effectiveness metrics.

PMID- 24279814
TI  - Genotoxic potential of two herbicides and their active ingredients assessed with
      comet assay on a fish cell line, epithelioma papillosum cyprini (EPC).
AB  - The aim of this study was to optimize the epithelioma papillosum cyprini (EPC)
      cell line handling procedure for the comet assay to investigate the genotoxic
      potential of widely used pesticides. The effects of various media and handling of
      the EPC cell line were examined. Results indicated that avoiding trypsin to
      detach cells led to lower level of DNA damage in the negative control. Further,
      two commonly used herbicides (Dezormon and Optica trio) and their four active
      ingredients (4-chloro-o-tolyloxyacetic acid, 2,4-dichlorophenoxyacetic acid, 2-(4
      chloro-2-methylphenoxy)propionic acid, 2-(2,4-dichlorophenoxy)propionic acid)
      individually and in a ternary mixture were examined with the comet assay. Data
      showed that among the active ingredients only 2,4-D and MCPA induced DNA damage,
      while both herbicides were genotoxic at high concentrations. 

PMID- 24279815
TI  - Trusted information sources used during and after Superstorm Sandy: TV and radio
      were used more often than social media.
AB  - Health and safety professionals and the public are interested in the best methods
      of providing timely information about disasters. The objective of this study was
      to examine information sources used for Superstorm Sandy with respect to the
      storm, evacuation routes, shelters, safety, and health issues. Respondents in
      central New Jersey and Jersey shore communities were differentially impacted by
      the storm. Jersey shore respondents had higher evacuation rates (47% vs. 13%),
      higher flood waters in homes, longer power outages (average 23 vs. 6 d), and
      longer periods without Internet (29 vs. 6 d). Electricity outages disrupted both
      sources and receivers of communication. Both groups obtained most of their
      information regarding safety from television, radio, friends, and Web/e-mail.
      Information sources on health varied by location, with central Jersey respondents
      using mainly TV and the Web, and Jersey shore respondents obtaining health
      information from the radio and TV (before the storm). For information on
      evacuation routes, Jersey shore respondents obtained information from many
      sources, while central Jersey respondents obtained it from TV. Information on
      mold was largely obtained from friends and the Web, since mold issues were dealt
      with several weeks after Sandy. The reliance on traditional sources of
      information (TV, radio, friends) found in this study suggests that the extreme
      power outages rendered Web, cell phones, and social media on cell phones less
      usable, and suggests the need for an integrated communication strategy with
      redundancies that takes into account prolonged power outages over large
      geographical areas. 

PMID- 24279816
TI  - Carbaryl and 1-naphthol tissue levels and related cholinesterase inhibition in
      male Brown Norway rats from preweaning to senescence.
AB  - Studies incorporating both toxicokinetic and dynamic factors provide insight into
      chemical sensitivity differences across the life span. Tissue (brain, plasma,
      liver) levels of the N-methyl carbamate carbaryl, and its metabolite 1-naphthol,
      were determined and related to brain and RBC cholinesterase (ChE) inhibition in
      the same animals. Dose-response (3, 7.5, 15, or 22.5 mg/kg, 40-45 min postdosing)
      and time course (3 or 15 mg/kg at 30, 60, 120, or 240 min postdosing) of acute
      effects of carbaryl (oral gavage) in preweanling (postnatal day [PND] 18) and
      adult male Brown Norway rats from adolescence to senescence (1, 4, 12, 24 mo)
      were compared. At all ages there were dose-related increases in carbaryl and 1
      naphthol in the dose-response study, and the time-course study showed highest
      carbaryl levels at 30 min postdosing. There were, however, age-related
      differences in that the 1- and 4-mo rats showed the lowest levels of carbaryl and
      1-naphthol, and PND18 and 24-mo rats had similar, higher levels. The fastest
      clearance (shortest half-lives) was observed in 1- and 4-mo rats. Carbaryl levels
      were generally higher than 1-naphthol in brain and plasma, but in liver, 1
      naphthol levels were similar to or greater than carbaryl. Brain ChE inhibition
      closely tracked brain carbaryl concentrations regardless of the time after
      dosing, but there was more variability in the relationship between RBC ChE and
      plasma carbaryl levels. Within-subject analyses suggested somewhat more brain ChE
      inhibition at lower carbaryl levels only in the PND18 rats. These findings may
      reflect maturation followed by decline in kinetic factors over the life span. 

PMID- 24279819
TI  - Evaluating the Massachusetts health care reform.

PMID- 24279817
TI  - Burrowing in the freshwater mussel Elliptio complanata is sexually dimorphic and
      feminized by low levels of atrazine.
AB  - The widely used herbicide atrazine (ATR) may have endocrine-associated adverse
      effects, including on behavior. In this study, 120 adult freshwater mussels,
      Elliptio complanata, were exposed to ATR at the environmentally relevant
      concentrations of 1.5, 15, or 150 MUg/L. Burrowing depth was evaluated hourly for
      6 h and at sacrifice animals were sexed by gonad smear. Female controls burrowed
      overall approximately 30% less than males, the first report of sexual dimorphism
      in this behavior. Atrazine at 15 MUg/L feminized burrowing in both sexes, in that
      exposed animals burrowed 20% less than their same-sex controls. Males treated
      with 1.5 MUg /L ATR displayed approximately 20-fold higher vitellogenin (VTG)
      levels than same-sex controls. Higher concentrations of ATR were not associated
      with increasing effects. A scatterplot showed a weak binomial curve associating
      low burrowing with high VTG levels. Taken together, these data suggest a
      nonlinear dose response in behavioral and physiological feminization produced by
      ATR and support the need to reconsider the widespread use of this compound. 

PMID- 24279818
TI  - Chemically engineered sulfated glucans from rice bran exert strong antiviral
      activity at the stage of viral entry.
AB  - Attachment and entry of many viruses are mediated by their affinity for
      polysaccharides present on the surface of target cells. In this paper, we
      demonstrate that sulfated glucans isolated from rice (Oryza sativa) can be
      utilized as experimental drugs exerting strong antiviral activity. In particular,
      oleum-DMF-based extraction is described as a procedure for the generation of
      chemically engineered glucans from commercially available rice bran. The one-step
      procedure has the potential to provide a spectrum of related glucans with varying
      molecular masses and modifications, including sulfation. The sulfated glucans
      P444, P445, and P446 possess increased antiviral activity compared to a
      previously described glucan (S1G). P444, P445, and P446 were highly active
      against human cytomegalovirus (HCMV), moderately active against other members of
      the family Herpesviridae, while not active against unrelated viruses. Specific
      experimentation with HCMV-infected cells provided evidence that antiviral
      activity was based on inhibition of viral entry and that inhibition occurred in
      the absence of drug-induced cytotoxicity. These findings underline the high
      potential of sulfated glucans for antiviral research and drug development. In
      addition, the procedure described for the efficient transformation of glucan
      hydroxy groups to sulfate groups may be similarly beneficial for the chemical
      alteration of other natural products. 

PMID- 24279820
TI  - Best of the AcademyHealth Annual Research Meeting.

PMID- 24279821
TI  - Roles for primary cilia in gonadotrophin-releasing hormone neurones in the mouse.
AB  - During embryonic development, gonadotrophin-releasing hormone (GnRH) neurones
      make an extraordinary migration out of the nose and into the brain where, in
      adulthood, they drive the pituitary regulation of gonadal function and fertility.
      Primary cilia are antennae-like, immotile organelles that project from the
      surface of nearly all cells, including GnRH neurones. Links between defects in
      primary cilia and a variety of human pathologies have been discovered that
      suggest a role for primary cilia in embryogenesis and reproductive function. The
      present study aimed to investigate whether GnRH neurone primary cilia are
      critical for their embryonic migration and the adult control of fertility. To
      achieve this, we used a Cre-loxP strategy to selectively disrupt primary cilia by
      deleting Kif3a, an intraflagellar transport protein family member essential for
      primary cilia assembly and function, specifically in GnRH neurones. Confocal
      analysis revealed that, in Kif3a(fl/fl) (WT-Kif3a) controls, all GnRH neurones
      possessed primary cilia, whereas, in GnRH-Cre(+/-) ;Kif3a(fl/fl) (GnRH-Kif3aKO)
      mice, 60% of GnRH neurones lacked any evidence of primary cilia and the remaining
      40% possessed only stunted primary cilia (< 2 MUm). Despite abolishing normal
      primary cilia assembly in GnRH neurones from embryogenesis, adult GnRH neurone
      distribution and reproductive function was remarkably normal. The total number of
      GnRH neurones was the same in GnRH-Kif3aKO and WT-Kif3a controls; however, a
      significant increase (25%) was identified in the number of GnRH neurones sampled
      through the midpoint of the rostral pre-optic area in GnRH-Kif3aKO mice (P <
      0.05). The time to vaginal opening was not different in GnRH-Kif3aKO mice,
      although they displayed significantly advanced first oestrus (P < 0.05), and
      oestrous cycle length was increased (P < 0.05). However, females displayed normal
      basal levels of luteinising hormone, responded normally to oestrogen-induced
      negative- and positive-feedback, and displayed normal fecundity. Taken together,
      these data suggest that primary cilia and associated signal transduction pathways
      play a role in the topographical distribution and specific functions of GnRH
      neurones; however, they are not essential for fertility.

PMID- 24279822
TI  - Purification and analysis of human alpha1-antitrypsin concentrate by a new
      immunoaffinity chromatography.
AB  - Alpha1-antitrypsin is a kind of plasma protein that requires a sequence of
      different fractionation steps to get generally. To report an effective process
      for isolating and purifying alpha1-antitrypsin from Cohn Fraction IV based upon a
      new immunoaffinity chromatography medium, named "Alpha-1 Antitrypsin Select,"
      characterization of alpha1-antitrypsin (alpha1-AT) was performed by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, and
      tandem mass spectroscopy. Total protein content was determined by the method of
      Bradford under visible light absorption at 595 nm. Pretreatment process and the
      immunoaffinity chromatography step achieved a 60.35 +/- 1.39% yield. Thus, an
      overall 71.68 +/- 1.32 fold increase in purity and a 41.88 +/- 6.98% yield were
      obtained from plasma. The alpha1-AT had a specific activity of about 1.00-1.05
      PU/mg. This technique will develop an effective process for isolating and
      purifying, with high purity and specific activity, alpha1-antitrypsin from Cohn
      Fraction IV or human whole plasma, which could be an efficient and scaled-up
      method for alpha1-antitrypsin products purification.

PMID- 24279823
TI  - High-performance flexible graphene aptasensor for mercury detection in mussels.
AB  - Mercury (Hg) is highly toxic but has been widely used for numerous domestic
      applications, including thermometers and batteries, for decades, which has led to
      fatal outcomes due to its accumulation in the human body. Although many types of
      mercury sensors have been developed to protect the users from Hg, few
      methodologies exist to analyze Hg(2+) ions in low concentrations in real world
      samples. Herein, we describe the fabrication and characterization of liquid-ion
      gated field-effect transistor (FET)-type flexible graphene aptasensor with high
      sensitivity and selectivity for Hg. The field-induced responses from the graphene
      aptasensor had excellent sensing performance, and Hg(2+) ions with very low
      concentration of 10 pM could be detected, which is 2-3 orders of magnitude more
      sensitive than previously reported mercury sensors using electrochemical systems.
      Moreover, the aptasensor showed a highly specific response to Hg(2+) ions in
      mixed solutions. The flexible graphene aptasensor showed a very rapid response,
      providing a signal in less than 1 s when the Hg(2+) ion concentration was
      altered. Specificity to Hg(2+) ions was demonstrated in real world samples (in
      this case samples derived from mussels). The aptasensor was fabricated by
      transferring chemical vapor deposition (CVD)-grown graphene onto a transparent
      flexible substrate, and the structure displayed excellent mechanical durability
      and flexiblility. This graphene-based aptasensor has potential for detecting Hg
      exposure in human and in the environment. 

PMID- 24279824
TI  - Pediococcus acidilactici UL5 and Lactococcus lactis ATCC 11454 are able to
      survive and express their bacteriocin genes under simulated gastrointestinal
      conditions.
AB  - AIMS: The aim of this work is to study the expression of stress genes and those
      involved in pediocin and nisin production in Pediococcus acidilactici UL5 and
      Lactococcus lactis ATCC11454 under simulated gastrointestinal (GI) physiological
      conditions. METHODS AND RESULTS: The two strains were fed to a dynamic GI model
      (TIM-1). Samples were taken from different compartments and analysed for strain
      survival as well as for the expression of pediocin PA-1 operon, nisin A
      production gene and stress genes using RT-qPCR. Ileal-delivered efflux showed a
      survival rate of 17 and 0.0007% for Ped. acidilactici and La. lactis,
      respectively. Pediocin operon genes from stressed cells were generally expressed
      at least at the same level as for unstressed cells. However, pedA is up-regulated
      in the effluent at 120 and 180 min. Nisin A genes were always up-regulated with
      particularly in the stomach after 70 min compared with control. CONCLUSIONS:
      Bacteriocin production of Ped. acidilactici UL5 and Lc. lactis ATCC 11454 are not
      affected by upper GI simulated conditions and thus could be considered as
      relevant probiotic candidates. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      demonstrates the capacity of lactic acid bacteria to survive and express their
      bacteriocins genes under simulated GI conditions.

PMID- 24279825
TI  - Phenotypic fitness of primary endothelial cells cultured from patients with high
      cardiovascular risk or chronic kidney disease for vascular tissue engineering.
AB  - Vascular tissue engineering relies on the combination of patient-derived cells
      and biomaterials to create new vessels. For clinical application, data regarding
      the function and behavior of patient-derived cells are needed. We investigated
      cell growth and functional characteristics of human venous endothelial cells
      (HVECs) from coronary arterial bypass graft (CABG), chronic kidney disease (CKD),
      and control patients. HVECs were isolated from venous specimens that were
      obtained during elective surgical procedures by means of collagenase digestion.
      Gene expression, proliferation, migration, secretory functions, and thrombogenic
      characteristics were evaluated using high-throughput assays. A total of 48 cell
      batches (14 control, 19 CABG, and 15 CKD subjects) were assessed. Proliferation,
      population doubling times, and migration of HVECs derived from CABG and CKD
      patients did not differ from controls. Thrombomodulin expression was higher in
      CABG-HVECs compared with controls. HVEC-induced thrombin formation in plasma did
      not differ between groups, and the contact activation pathway was the major
      contributor to coagulation. Patient-derived HVECs were able to attach and survive
      on polycaprolactone scaffolds that were coated with fibrin. HVECs from
      cardiovascular-diseased and CKD patients showed comparable functional
      characteristics with HVECs derived from uncompromised patients. We, therefore,
      conclude that endothelial cells from aged patients with comorbidities can be
      safely used for isolation and in vitro expansion for vascular tissue engineering.

PMID- 24279826
TI  - Validity of actigraphs uniaxial and triaxial accelerometers for assessment of
      physical activity in adults in laboratory conditions.
AB  - BACKGROUND: Few studies to date have directly compared the Actigraphs GT1M and
      the GT3X, it would be of tremendous value to know if these accelerometers give
      similar information about intensities of PA. Knowing if output is similar would
      have implications for cross-examination of studies. The purpose of the study was
      to assess the validity of the GT1M and the GT3X Actigraph accelerometers for the
      assessment of physical activity against oxygen consumption in laboratory
      conditions. METHODS: Forty-two college-aged participants aged 18-25 years wore
      the GT1M and the GT3X on their right hip during treadmill exercise at three
      different speeds, slow walking 4.8 km.h-1, fast walking 6.4 km.h-1, and running
      9.7 km.h-1). Oxygen consumption was measured minute-by minute using a metabolic
      system. Bland-Altman plots were used to assess agreement between activity counts
      from the GT3X and GT1M, and correlations were assessed the ability of the
      accelerometers to assess physical activity. RESULTS: Bias for 4.8 km.h-1 was
      2814.4 cpm (limits 1211.3 to 4417.4), for 6.4 km.h-1 was 3713.6 cpm (limits
      1573.2 to 5854.0), and for 9.7 km.h-1 was-3811.2 cpm (limits 842.1 to 6780.3).
      Correlations between counts per minute for the GT1M and the GT3X were
      significantly correlated with VO2 (r = 0.881, p < 0.001; r = 0.810, p < 0.001
      respectively). CONCLUSION: The present study showed that both the GT1M and the
      GT3X accurately measure physical activity when compared to oxygen consumption.

PMID- 24279827
TI  - Multimorbidity of chronic diseases among adult patients presenting to an inner
      city clinic in Ghana.
AB  - BACKGROUND: Very little is known about multimorbidity and chronic diseases in low
      and middle income countries, particularly Sub-Saharan Africa, and more
      information is needed to guide the process of adapting the health systems in
      these countries to respond adequately to the increasing burden of chronic
      diseases. We conducted a hospital-based survey in an urban setting in Ghana to
      determine the prevalence of multimorbidity and its associated risk factors among
      adult patients presenting to an inner city clinic. METHODS: Between May and June
      2012, we interviewed adult patients (aged 18 years and above) attending a routine
      outpatient clinic at an inner-city hospital in Accra using a structured
      questionnaire. We supplemented the information obtained from the interviews with
      information obtained from respondents' health records. We used logistic
      regression analyses to explore the risk factors for multimorbidity. RESULTS: We
      interviewed 1,527 patients and retrieved matching medical records for 1,399
      (91.6%). The median age of participants was 52.1 years (37-64 years). While the
      prevalence of multimorbidity was 38.8%, around half (48.6%) of the patients with
      multimorbidity were aged between 18-59 years old. The most common combination of
      conditions was hypertension and diabetes mellitus (36.6%), hypertension and
      musculoskeletal conditions (19.9%), and hypertension and other cardiovascular
      conditions (11.4%). Compared with patients aged 18-39 years, those aged 40-49
      years (OR 4.68, 95% CI: 2.98-7.34), 50-59 years (OR 12.48, 95% CI: 8.23-18.92)
      and 60 years or older (OR 15.80, 95% CI: 10.66-23.42) were increasingly likely to
      present with multimorbidity. While men were less likely to present with
      multimorbidity, (OR 0.71, 95% CI: 0.45-0.94, p = 0.015), having a family history
      of any chronic disease was predictive of multimorbidity (OR 1.43, 95% CI: 1.03
      1.68, p = 0.027). CONCLUSIONS: Multimorbidity is a significant problem in this
      population. By identifying the risk factors for multimorbidity, the results of
      the present study provide further evidence for informing future policies aimed at
      improving clinical case management, health education and medical training in
      Ghana.

PMID- 24279828
TI  - Impact of rituximab desensitization on blood-type-incompatible adult living donor
      liver transplantation: a Japanese multicenter study.
AB  - We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type
      incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult
      patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or
      triple immunosuppression with or without B cell desensitization therapies such as
      plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and
      rituximab. Era before 2005, intensive care unit-bound status, high Model for End
      Stage Liver Disease score and absence of rituximab prophylaxis were significant
      risk factors for overall survival and antibody-mediated rejection (AMR) in the
      univariate analysis. After adjustment for era effects in the multivariate
      analysis, only absence of rituximab prophylaxis was a significant risk factor for
      AMR, and there were no significant risk factors for survival. Rituximab
      prophylaxis significantly decreased the incidence of AMR, especially hepatic
      necrosis (p < 0.001). In the rituximab group, other B cell desensitization
      therapies had no add-on effects. Multiple or large rituximab doses significantly
      increased the incidence of infection, and early administration had no advantage.
      In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the
      latest era coincident with the introduction of rituximab.

PMID- 24279829
TI  - Weeding out the information: an ethnographic approach to exploring how young
      people make sense of the evidence on cannabis.
AB  - BACKGROUND: Contradictory evidence on cannabis adds to the climate of confusion
      regarding the health harms related to use. This is particularly true for young
      people as they encounter and make sense of opposing information on cannabis.
      Knowledge translation (KT) is in part focused on ensuring that knowledge users
      have access to and understand best evidence; yet, little attention has focused on
      the processes youth use to weigh scientific evidence. There is growing interest
      in how KT efforts can involve knowledge users in shaping the delivery of youth
      focused public health messages. To date, the youth voice has been largely absent
      from the creation of public health messages on cannabis. METHODS: This
      ethnographic study describes a knowledge translation project that focused on
      engaging young people in a review of evidence on cannabis that concluded with the
      creation of public health messages generated by youth participants. We
      facilitated two groups with a total of 18 youth participants. Data included
      transcribed segments of weekly sessions, researcher field notes, participant
      research logs, and transcribed follow-up interviews. Qualitative, thematic
      analysis was conducted. RESULTS: Group dynamics were influential in terms of how
      participants made sense of the evidence. The processes by which participants came
      to understand the current evidence on cannabis are described, followed by the
      manner in which they engaged with the literature for the purpose of creating an
      individual public health message to share with the group. At project end, youth
      created collaborative public health messages based on their understanding of the
      evidence illustrating their capacity to "weed out" the information. The content
      of these messages reflect a youth-informed harm reduction approach to cannabis
      use. CONCLUSIONS: This study demonstrates the feasibility of involving young
      people in knowledge translation initiatives that target peers. Youth participants
      demonstrated that they were capable of reading scientific literature and had the
      capacity to engage in the creation of evidence-informed public health messages on
      cannabis that resonate with young people. Rather than simply being the target of
      KT messages, they embraced the opportunity to engage in dialogue focused on
      cannabis.

PMID- 24279830
TI  - MicroRNA-326 regulates profibrotic functions of transforming growth factor-beta
      in pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal disorder resulting from the
      progressive remodeling of lungs, with no known effective treatment. Although
      transforming growth factor (TGF)-beta has a well-established role in lung
      fibrosis, clinical experience with neutralizing antibodies to TGF-beta has been
      disappointing, and strategies to directly suppress TGF-beta1 secretion are
      needed. In this study we used a combination of in silico, in vitro, and in vivo
      approaches to identify microRNAs involved in TGF-beta1 regulation and to validate
      the role of miR-326 in pulmonary fibrosis.We show that hsa-miR-326 regulates TGF
      beta1 expression and that hsa-miR-326 levels are inversely correlated to TGF
      beta1 protein levels in multiple human cell lines. The increase in TGF-beta1
      expression during the progression of bleomycin-induced lung fibrosis in mice was
      associated with loss of mmu-miR-326. Restoration of mmu-miR-326 levels by
      intranasal delivery of miR-326 mimics was sufficient to inhibit TGF-beta1
      expression and attenuate the fibrotic response. Moreover, human IPF lung
      specimens had markedly diminished miR-326 expression as compared with nonfibrotic
      lungs. Additional targets of miR-326 controlling TGF-beta signaling and fibrosis
      related pathways were identified, and miR-326 was found to down-regulate
      profibrotic genes, such as Ets1, Smad3, and matrix metalloproteinase 9, whereas
      it up-regulates antifibrotic genes, such as Smad7. Our results suggest for the
      first time that miR-326 plays a key role in regulating TGF-beta1 expression and
      other profibrotic genes and could be useful in developing better therapeutic
      strategies for alleviating lung fibrosis.

PMID- 24279831
TI  - Mechanical tissue resuscitation protects against myocardial ischemia-reperfusion
      injury.
AB  - BACKGROUND AND AIM: Reperfusion injury is a complex inflammatory response
      involving numerous mechanisms and pathways. Mechanical tissue resuscitation is a
      newly described therapeutic strategy that reduces reperfusion injury. This study
      further investigates potential mechanisms for the protective effects of
      mechanical tissue resuscitation while utilizing a bio-absorbable matrix. METHODS:
      Anesthetized swine were subjected to 80 minutes of coronary ischemia and three
      hours of reperfusion. An absorbable matrix was used to cover the ischemic
      reperfused myocardium and apply the mechanical tissue resuscitation (-50 mmHg)
      throughout reperfusion. Infarct size, myocardial blood flow (microspheres),
      apoptosis, edema, and hemodynamics were analyzed. RESULTS: Both control and
      treated groups displayed similar hemodynamics and physiologic parameters.
      Mechanical tissue resuscitation significantly reduced early infarct size (16.6 +/
      3.8% vs. 27.3 +/- 2.5% of area at risk, p < 0.05). This reduction of infarct
      size was accompanied by reduced edema formation in both epicardial (27%
      reduction) and endocardial (58% reduction) samples. Histological examination of
      both epicardial and endocardial tissues also revealed a reduction in apoptosis
      (80% and 44% reductions) in MTR-treated hearts. CONCLUSIONS: Treatment with
      mechanical tissue resuscitation during reperfusion reduces both early cell death
      and the delayed, programmed cell death after ischemia-reperfusion. This
      cardioprotection is also associated with a significant reduction in interstitial
      water. Additional cardioprotection may be derived from mechanical tissue
      resuscitation-induced increased blood flow. Mechanical tissue resuscitation,
      particularly with a resorbable device, is a straightforward and efficacious
      mechanical strategy for decreasing cardiomyocyte death following myocardial
      infarction as an adjunctive therapy to surgical revascularization.

PMID- 24279832
TI  - Phenomics of rice early vigour and drought response: Are sugar related and
      morphogenetic traits relevant?
AB  - BACKGROUND: Early vigour (biomass accumulation) is a useful but complex trait in
      rainfed rice (Oryza sativa L). Little is known on trade-offs with drought
      tolerance. This study explored the relevance of (sugar) metabolic and
      morphogenetic traits to describe the genetic diversity of rice early vigour and
      its phenotypic plasticity under drought conditions. A greenhouse experiment was
      conducted to characterize on a panel of 43 rice genotypes plant morphogenesis and
      sugar concentration in expanded (source) and expanding (sink) leaves. RESULTS:
      Across genotypes in control treatment, leaf starch concentration was negatively
      correlated with organogenetic development rate (DR, defined as leaf appearance
      rate on main stem). Genotypes with small leaves had high DR and tiller number but
      low leaf starch concentration. Under drought, vigorous genotypes showed stronger
      growth reduction. Starch concentration decreased in source leaves, by contrast
      with soluble sugars and with that observed in sink leaves. Accordingly, genotypes
      were grouped in three clusters differing in constitutive vigour, starch storage
      and growth maintenance under drought showing a trade off between constitutive
      vigour and drought tolerance. CONCLUSIONS: It was therefore suggested that non
      structural carbohydrates, particularly starch, were relevant markers of early
      vigour. Their relevance as markers of growth maintenance under drought needs to
      be further explored. Results are discussed regarding novel process based traits
      to be introduced in the GRiSP (Global Rice Science Partnership) phenotyping
      network.

PMID- 24279833
TI  - Determining the specificity of monoclonal antibody HPT-101 to tau-peptides with
      optical tweezers.
AB  - Optical tweezers-assisted dynamic force spectroscopy is employed to investigate
      specific receptor-ligand interactions on the level of single binding events. In
      particular, we analyze binding of the phosphorylation-specific monoclonal
      antibody (mAb) HPT-101 to synthetic tau-peptides with two potential
      phosphorylation sites (Thr231 and Ser235), being the most probable markers for
      Alzheimer's disease. Whereas the typical interpretation of enzyme-linked
      immunosorbent assay (ELISA) suggests that this monoclonal antibody binds
      exclusively to the double-phosphorylated tau-peptide, we show here by DFS that
      the specificity of only mAb HPT-101 is apparent. In fact, binding occurs also to
      each sort of monophosphorylated peptide. Therefore, we characterize the unbinding
      process by analyzing the measured rupture force distributions, from which the
      lifetime of the bond without force tau0, its characteristic length xts, and the
      free energy of activation DeltaG are extracted for the three mAb/peptide
      combinations. This information is used to build a simple theoretical model to
      predict features of the unbinding process for the double-phosphorylated peptide
      purely based on data on the monophosphorylated ones. Finally, we introduce a
      method to combine binding and unbinding measurements to estimate the relative
      affinity of the bonds. The values obtained for this quantity are in accordance
      with ELISA, showing how DFS can offer important insights about the dynamic
      binding process that are not accessible with this common and widespread assay. 

PMID- 24279834
TI  - Integrating mixed methods in health services and delivery system research.

PMID- 24279835
TI  - Achieving integration in mixed methods designs-principles and practices.
AB  - Mixed methods research offers powerful tools for investigating complex processes
      and systems in health and health care. This article describes integration
      principles and practices at three levels in mixed methods research and provides
      illustrative examples. Integration at the study design level occurs through three
      basic mixed method designs-exploratory sequential, explanatory sequential, and
      convergent-and through four advanced frameworks-multistage, intervention, case
      study, and participatory. Integration at the methods level occurs through four
      approaches. In connecting, one database links to the other through sampling. With
      building, one database informs the data collection approach of the other. When
      merging, the two databases are brought together for analysis. With embedding,
      data collection and analysis link at multiple points. Integration at the
      interpretation and reporting level occurs through narrative, data transformation,
      and joint display. The fit of integration describes the extent the qualitative
      and quantitative findings cohere. Understanding these principles and practices of
      integration can help health services researchers leverage the strengths of mixed
      methods.

PMID- 24279837
TI  - Artificial synthesis of swine hepcidin gene and expression in Pichia pastoris.
AB  - In order to express swine hepcidin gene in Pichia pastoris, a DNA fragment coding
      hepcidin gene was synthesized with adaptation to yeast codon usage of highly
      expressed genes. A Kex2 signal cleavage site was fused in the 5' end of the DNA
      fragment for getting a peptide with the same N-end as native hepcidin. The 96-bp
      DNA fragment was ligated into the expression plasmid of pGAPZaA to construct
      pGAPZaA-hepcidin vector, which was transferred into P. pastoris (X33) to express
      hepcidin gene for extracellular secretion of protein at 86 ug/mL. A band of 2.76
      kD molecular mass was detected by Tricine sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis (PAGE) analysis. Through antibacterial assay,
      the expressed hepcidin displayed obvious antibacterial activity. The minimal
      inhibitory concentration (MIC) was 5.38 and 2.69 ug/mL for Staphylococcus aureus
      and Bacillus subtilis prolification inhibitions, respectively.

PMID- 24279836
TI  - Connecting the dots and merging meaning: using mixed methods to study primary
      care delivery transformation.
AB  - OBJECTIVE: To demonstrate the value of mixed methods in the study of practice
      transformation and illustrate procedures for connecting methods and for merging
      findings to enhance the meaning derived. DATA SOURCE/STUDY SETTING: An integrated
      network of university-owned, primary care practices at the University of Utah
      (Community Clinics or CCs). CC has adopted Care by Design, its version of the
      Patient Centered Medical Home. STUDY DESIGN: Convergent case study mixed methods
      design. DATA COLLECTION/EXTRACTION METHODS: Analysis of archival documents,
      internal operational reports, in-clinic observations, chart audits, surveys,
      semistructured interviews, focus groups, Centers for Medicare and Medicaid
      Services database, and the Utah All Payer Claims Database. PRINCIPAL FINDINGS:
      Each data source enriched our understanding of the change process and
      understanding of reasons that certain changes were more difficult than others
      both in general and for particular clinics. Mixed methods enabled generation and
      testing of hypotheses about change and led to a comprehensive understanding of
      practice change. CONCLUSIONS: Mixed methods are useful in studying practice
      transformation. Challenges exist but can be overcome with careful planning and
      persistence.

PMID- 24279838
TI  - Static vs dynamic settlement and adhesion of diatoms to ship hull coatings.
AB  - Many experiments utilize static immersion tests to evaluate the performance of
      ship hull coatings. These provide valuable data; however, they do not accurately
      represent the conditions both the hull and fouling organisms encounter while a
      ship is underway. This study investigated the effect of static and dynamic
      immersion on the adhesion and settlement of diatoms to one antifouling coating
      (BRA 640), four fouling-release coatings (Intersleek((r)) 700, Intersleek((r))
      900, Hempasil X3, and Dow Corning 3140) and one standard surface (Intergard((r))
      240 Epoxy). Differences in community composition were observed between the static
      and dynamic treatments. Achnanthes longipes was present on all coatings under
      static immersion, but was not present under dynamic immersion. This was also
      found for diatoms in the genera Bacillaria and Gyrosigma. Melosira moniformis was
      the only diatom present under dynamic conditions, but not static conditions.
      Several common fouling diatom genera were present on panels regardless of
      treatment: Amphora, Cocconeis, Entomoneis Cylindrotheca, Licmophora, Navicula,
      Nitzschia, Plagiotropis, and Synedra. Biofilm adhesion, diatom abundance and
      diatom diversity were found to be significantly different between static and
      dynamic treatments; however, the difference was dependent on coating and sampling
      date. Several coatings (Epoxy, DC 3140 and IS 700) had significantly higher
      biofilm adhesion on dynamically treated panels on at least one of the four
      sampling dates, while all coatings had significantly higher diatom abundance on
      at least one sampling date. Diversity was significantly greater on static panels
      than dynamic panels for Epoxy, IS 700 and HX3 at least once during the sampling
      period. The results demonstrate how hydrodynamic stress will significantly
      influence the microfouling community. Dynamic immersion testing is required to
      fully understand how antifouling surfaces will respond to biofilm formation when
      subjected to the stresses experienced by a ship underway. 

PMID- 24279839
TI  - Atrial remodelling is less pronounced in female endurance-trained athletes
      compared with that in male athletes.
AB  - OBJECTIVES: Little data exists on atrial adaptation to training in women.
      Furthermore, data on right atrial (RA) volumes is lacking for both male and
      female athletes. The objective of this study was therefore to investigate atrial
      volumes in male and female athletes. DESIGN: A total of 75 athletes (33 women)
      and 53 controls (21 women) underwent cardiovascular magnetic resonance imaging.
      Left atrial (LA) and RA volumes were measured by manual delineation. The atrial
      appendage was included in the volumes, and pulmonary veins were excluded.
      RESULTS: Atrial volumes were larger in athletes compared with those in controls
      (males: LA 116 +/- 19 ml versus 93 +/- 19 ml, RA 166 +/- 32 ml versus 133 +/- 23
      ml, p < 0.0001, females: LA 90 +/- 15 ml versus 83 +/- 17 ml, p < 0.05, RA 119 +/
      24 ml versus 108 +/- 18 ml, p = 0.07). When normalized for body surface area,
      atrial volumes remained larger in athletes. However, when normalized for total
      heart volume (THV) there were no differences between groups except for LA volumes
      in females where controls had higher LA/THV compared with those in athletes (p <
      0.05). CONCLUSION: Atrial volumes were significantly larger in athletes. Atrial
      volumes normalized for THV did not differ between athletes and controls
      indicating a balanced enlargement. There was only a small difference between
      female controls and female athletes, suggesting that atrial adjustment to
      training is more modest in women.

PMID- 24279840
TI  - Plasmonic surface lattice resonances at the strong coupling regime.
AB  - We show strong coupling involving three different types of resonances in
      plasmonic nanoarrays: surface lattice resonances (SLRs), localized surface
      plasmon resonances on single nanoparticles, and excitations of organic dye
      molecules. The measured transmission spectra show splittings that depend on the
      molecule concentration. The results are analyzed using finite-difference time
      domain simulations, a coupled-dipole approximation, coupled-modes models, and
      Fano theory. The delocalized nature of the collective SLR modes suggests that in
      the strong coupling regime molecules near distant nanoparticles are coherently
      coupled. 

PMID- 24279842
TI  - Grafting-responsive miRNAs in cucumber and pumpkin seedlings identified by high
      throughput sequencing at whole genome level.
AB  - Grafting is an important agricultural technique widely used for improving growth,
      yields and tolerance of crops to abiotic and biotic stresses. As one type of
      endogenous, non-coding small RNAs, microRNAs (miRNAs) regulate development and
      responsiveness to biotic and abiotic stresses by negatively mediating expression
      of target genes at the post-transcriptional level. However, there have been few
      detailed studies to evaluate the role of miRNAs in mediation of grafting-induced
      physiological processes in plants. Cucumis sativus and Cucurbita moschata are
      important vegetables worldwide. We constructed eight small RNA libraries from
      leaves and roots of seedlings that were grafted in the following four ways: (1)
      hetero-grafting, using cucumber as scion and pumpkin as rootstock; (2) hetero
      grafting, with pumpkin as scion and cucumber as rootstock; (3) auto-grafting of
      cucumbers and (4) auto-grafting of pumpkins. High-throughput sequencing was
      employed, and more than 120 million raw reads were obtained. We annotated 112
      known miRNAs belonging to 40 miRNA families and identified 48 new miRNAs in the
      eight libraries, and the targets of these known and novel miRNAs were predicted
      by bioinformatics. Grafting led to changes in expression of most miRNAs and their
      predicted target genes, suggesting that miRNAs may play significant roles in
      mediating physiological processes of grafted seedlings by regulating the
      expression of target genes. The potential role of the grafting-responsive miRNAs
      in seedling growth and long-distance transport of miRNA was discussed. These
      results are useful for functional characterization of miRNAs in mediation of
      grafting-dependent physiological processes. 

PMID- 24279841
TI  - Internet-based treatment of major depression for patients on a waiting list for
      inpatient psychotherapy: protocol for a multi-centre randomised controlled trial.
AB  - BACKGROUND: Major depressive disorder (MDD) is a prevalent and severe disorder.
      Although effective treatments for MDD are available, many patients remain
      untreated, mainly because of insufficient treatment capacities in the health care
      system. Resulting waiting periods are often associated with prolonged suffering
      and impairment as well as a higher risk of chronification. Web-based
      interventions may help to alleviate these problems. Numerous studies provided
      evidence for the efficacy of web-based interventions for depression. The aim of
      this study is to evaluate a new web-based guided self-help intervention (GET.ON
      Mood Enhancer-WL) specifically developed for patients waiting to commence
      inpatient therapy for MDD. METHODS: In a two-armed randomised controlled trial (n
      = 200), the web-based guided intervention GET.ON-Mood Enhancer-WL in addition to
      treatment as usual (TAU) will be compared with TAU alone. The intervention
      contains six modules (psycho education, behavioural activation I & II, problem
      solving I & II, and preparation for subsequent inpatient depression therapy). The
      participants will be supported by an e-coach, who will provide written feedback
      after each module. Inclusion criteria include a diagnosis of MDD assessed with a
      structured clinical interview [SCID] and a waiting period of at least three weeks
      before start of inpatient treatment. The primary outcome is observer-rated
      depressive symptom severity (HRSD24). Further (explorative) questions include
      whether remission will be achieved earlier and by more patients during inpatient
      therapy because of the web-based preparatory intervention. DISCUSSION: If GET.ON
      Mood Enhancer-WL is proven to be effective, patients may start inpatient therapy
      with reduced depressive symptom severity, ideally leading to higher remission
      rates, shortened inpatient therapy, reduced costs, and decreased waiting times.
      TRIAL REGISTRATION: German Clinical Trial Registration (DRKS): DRKS00004708.

PMID- 24279843
TI  - Naturally occuring canine cancers: powerful models for stimulating
      pharmacogenomic advancement in human medicine.

PMID- 24279844
TI  - Polymorphic OCT1: a valid biomarker, but for which drugs?

PMID- 24279845
TI  - ADRB2 Arg16 and the need for collaboration in childhood asthma pharmacogenomics.

PMID- 24279846
TI  - In Chan et al. the difference between p < 0.05 and p < 0.05 is p > 0.05.

PMID- 24279847
TI  - Comparing self-reported ethnicity and structure-determined ethnicity: analysis of
      antipsychotic-induced weight gain.

PMID- 24279849
TI  - Tumor heterogeneity and response to chemotherapy.

PMID- 24279850
TI  - Conference Scene: Systems biology and personalized health science and
      translation.
AB  - After a 1-day advanced course on systems biology, the main themes of this 3-day
      colloquium were developed: from systems biology to systems medicine with special
      applications to cancer; pharmacogenomics in drug discovery and clinical
      application; and epigenomics and genome-wide association studies in
      cardiovascular diseases. In two roundtable discussions on pharmacogenomics and
      genome-wide association studies, the progress and the difficulties in the
      implementation of omics technologies in clinical practice were discussed. Three
      workshops were also organized on technical tools linked to the meeting themes. 

PMID- 24279851
TI  - Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a
      reported use of long-acting beta2-agonists: results of the PACMAN cohort.
AB  - BACKGROUND: Current evidence suggests that asthma patients with the ADRB2 Arg16
      genotype have a poorer response to long-acting beta2-agonists (LABA), but the
      results remain inconsistent. AIM: This study assessed the association between
      Arg16 variants and treatment outcome in children treated with inhaled
      corticosteroids (ICS) and LABA. MATERIALS & METHODS: ADRB2 Arg16 was genotyped in
      597 children (4-12 years of age) participating in the PACMAN cohort study. A
      questionnaire was used to assess asthma control, frequency of asthma-related
      emergency department visits and use of oral corticosteroids in the past year.
      RESULTS: Arg/Arg carriers with a reported use of ICS and LABA had an increased
      risk of oral corticosteroid use (odds ratio: 14.9; 95% CI: 1.59-140.1) and
      emergency department visits in the past year (odds ratio: 11.9; 95% CI: 1.22
      115.8) compared to Gly/Gly carriers. This effect was not observed in Arg/Arg
      genotype carriers reporting ICS use only. CONCLUSION: Children who are homozygous
      for ADRB2 Arg16 have an increased risk of exacerbations when treated with
      combined LABA and ICS.

PMID- 24279853
TI  - Integrative mouse and human mRNA studies using WGCNA nominates novel candidate
      genes involved in the pathogenesis of major depressive disorder.
AB  - AIM: This study aims to identify novel genes associated with major depressive
      disorder and pharmacological treatment response using animal and human mRNA
      studies. MATERIALS & METHODS: Weighted gene coexpression network analysis was
      used to uncover genes associated with stress factors in mice and to inform mRNA
      probe set selection in a post-mortem study of depression. RESULTS: A total of 171
      genes were found to be differentially regulated in response to both early and
      late stress protocols in a mouse study. Ten human genes, orthologous to mouse
      genes differentially expressed by stress, were also found to be dysregulated in
      depressed cases in a human post-mortem brain study from the Stanley Foundation
      Brain Collection. CONCLUSION: Several novel genes associated with depression were
      uncovered, including NOVA1 and USP9X. Moreover, we found further evidence in
      support of hippocampal neurogenesis and peripheral inflammation in major
      depressive disorder.

PMID- 24279852
TI  - CYP2D6 -1584C>G promoter polymorphism and debrisoquine ultrarapid hydroxylation
      in healthy volunteers.
AB  - BACKGROUND & AIM: The CYP2D6 -1584C>G polymorphism (rs1080985) has been
      identified as a major factor for CYP2D6 expression and function, with the mutant 
      1584G promoter type being consistently associated with significantly greater
      expression than -1584C. It may therefore be associated with ultrarapid
      metabolism. The objective of the present study was to explore the relationship
      between the CYP2D6 -1584C>G polymorphism and the debrisoquine metabolic ratio in
      healthy volunteers in order to evaluate its potential impact on the ultrarapid
      CYP2D6 hydroxylation capacity. MATERIALS & METHODS: The CYP2D6 -1584C>G
      polymorphism was analyzed in 320 unrelated healthy individuals who were
      previously phenotyped for debrisoquine hydroxylation. RESULTS: The metabolic
      ratio (log10 mean +/- standard deviation) of individuals with the -1584G allele
      was lower than that of individuals with the -1584C allele for carriers of one
      active CYP2D6 gene (-0.13 +/- 0.33 and 0.17 +/- 0.52, respectively; p < 0.05) or
      two active CYP2D6 genes (-0.32 +/- 0.39 and -0.20 +/- 0.44, respectively; p <
      0.05). CONCLUSION: The presence of the -1584G allele in the promoter region of
      the CYP2D6 gene was related to a high CYP2D6 hydroxylation capacity.

PMID- 24279854
TI  - Mitochondrial subhaplogroups and differential risk of stavudine-induced
      lipodystrophy in Malawian HIV/AIDS patients.
AB  - BACKGROUND & AIM: Lipodystrophy remains a significant problem in HIV/AIDS
      patients, especially those on regimens containing either protease inhibitors or
      thymidine analogs (stavudine or zidovudine). Many of the manifestations of
      lipodystrophy have been linked to mitochondrial dysfunction. We set out to
      investigate whether mtDNA variation is associated with the development of
      stavudine-induced lipodystrophy among adult Malawian HIV/AIDS patients on
      antiretroviral therapy that included stavudine. MATERIALS & METHODS: A total of
      117 adult HIV/AIDS patients on stavudine-containing antiretroviral therapy (ART)
      were recruited from the ART clinic at the Queen Elizabeth Central Hospital,
      Malawi. The patients were categorized according to whether or not they had
      developed lipodystrophy after being on a stavudine-containing ART regimen for at
      least 6 months. Whole mtDNA-coding regions of each patient were sequenced and
      correlated with clinical characteristics. RESULTS: Lipodystrophy was apparent in
      16% (n = 19) of the participants. In multivariate analysis, age >40 years (odds
      ratio: 4.43; 95% CI: 1.36-14.47; p = 0.014) was significantly associated with the
      presence of lipodystrophy. The mtDNA subhaplogroup L3e appeared to be protective
      against lipodystrophy, as none of 11 subjects with this subhaplogroup presented
      with lipodystrophy. CONCLUSION: mtDNA subhaplogroups seem to differentially
      affect susceptibility to lipodystrophy. More research is required in order to
      identify patients who are more or less likely to benefit from stavudine
      containing ART.

PMID- 24279855
TI  - Concordance of genotype for polymorphisms in DNA isolated from peripheral blood
      and colorectal cancer tumor samples.
AB  - BACKGROUND & AIM: Results from different pharmacogenetic association studies in
      colorectal cancer are often conflicting. Both peripheral blood and formalin
      fixed, paraffin-embedded (FFPE) tissue are routinely used as DNA source. This
      could cause bias due to somatic alterations in tumor tissue, such as loss of
      heterozygosity. We therefore compared genotypes in DNA from peripheral blood and
      FFPE colorectal tumor samples for SNPs with putative influence on the
      cytotoxicity of chemotherapy. MATERIALS & METHODS: Eleven SNPs in nine genes
      involved in anticancer drug metabolism or efficacy were determined in matched
      samples from blood and FFPE tissue of colorectal tumors by pyrosequencing and
      TaqMan((r)) techniques. The kappa-statistic was calculated to assess concordance.
      RESULTS: A total of 149 paired FFPE tissue and EDTA blood DNA samples were
      available for comparison. Overall, 20 out of 1418 genotypes were discordant
      (1.4%); in ten cases, loss of heterozygosity could not be ruled out. Only GSTP1
      showed significant discordance between FFPE tissue and blood genotype (kappa =
      0.947; 95% CI: 0.896-0.998). CONCLUSION: FFPE tissue-derived DNA can be used as a
      valid proxy for germline DNA for a selection of SNPs in (retrospective)
      pharmacogenetic association studies in colorectal cancer. However, for future
      studies, genotyping of blood-derived DNA is preferred.

PMID- 24279856
TI  - Cost-effectiveness of using CYP2C19 genotype to guide selection of clopidogrel or
      ticagrelor in Australia.
AB  - AIMS: This study aims to assess the cost-effectiveness in Australia of screening
      CYP2C19 loss-of-function (LoF) alleles to guide selection of clopidogrel or
      ticagrelor for individuals with acute coronary syndrome who are likely to undergo
      coronary stenting. METHODS: Three treatment strategies were compared: universal
      clopidogrel therapy, universal ticagrelor therapy and genotyping CYP2C19 with use
      of ticagrelor for individuals with a LoF allele and clopidogrel for individuals
      without a LoF allele. Lifetime costs and quality-adjusted life years for each
      treatment strategy were estimated using a Markov model. The risks of events were
      primarily derived from the genetic substudy of the pivotal randomized controlled
      trial. RESULTS: CYP2C19 genotyping resulted in greater effectiveness and was cost
      effective when compared with universal use of clopidogrel. However, universal use
      of ticagrelor was the most effective strategy overall and the incremental cost
      effectiveness compared with the genotyping strategy was generally within what is
      considered acceptable. CONCLUSION: Ticagrelor is likely to be cost-effective even
      for individuals not carrying a CYP2C19 LoF allele.

PMID- 24279858
TI  - Pharmacogenetics of the nuclear hormone receptors: the missing link between
      environment and drug effects?
AB  - In the last decade, genetic variations in ABC/SLC transporters and phase I/II
      enzymes have raised pharmacogenetic markers as being predictive to the attention
      of researchers in the field of personalized medicine in oncology. However, it is
      becoming evident that the sequence variations in these genes cannot address by
      themselves the sharp interindividual variability in drug effects. Recently,
      nuclear receptors (NRs), including pregnane X receptor, constitutive androstane
      receptor, retinoid X receptor, farnesoid X receptor, liver X receptor, vitamin D
      receptor, peroxisome proliferator-activated receptors and HNF4A, have
      demonstrated key roles in regulating transporter and metabolic gene expression in
      response to xeno/endobiotics, as well as antineoplastic drugs. These findings
      attracted interest to the genetics of the NRs for their possible role in
      influencing the metabolism and pharmacological profiles of chemotherapeutics. In
      this review, we aim to summarize the most recent findings in the innovative field
      of NR pharmacogenetics and findings in how they could integrate with more
      traditional markers in order to improve drug treatment personalization. 

PMID- 24279857
TI  - Not so pseudo anymore: pseudogenes as therapeutic targets.
AB  - Pseudogenes are junk DNA gene remnants generated by inactivating mutations or the
      loss of regulatory sequences, often following gene duplication or
      retrotransposition events. These pseudogenes have previously been considered to
      be molecular fossils derived from once-coding genes. In many cases, pseudogenes
      confer no observable selective advantage to the host organism and may be on a
      path towards removal from the genome. However, pseudogenes can also serve as raw
      material for the exaptation of novel functions, particularly in relation to the
      regulation of gene expression. Many pseudogenes are resurrected as noncoding RNA
      genes, which function in RNA-based gene regulatory circuits. As such, functional
      pseudogenes might simply be considered as 'genes'. Here, we discuss the role of
      these pseudogene-derived RNAs as regulators of gene expression in the context of
      human disease. In particular, we consider the manipulation of pseudogene
      transcripts through the use of antisense oligonucleotides, siRNAs, aptamers or
      classical gene therapy approaches as novel pharmacological strategies. 

PMID- 24279859
TI  - BDNF rs6265 polymorphism and drug addiction: a systematic review and meta
      analysis.
AB  - A majority of studies have shown a link between the common functional rs6265
      polymorphism of the BDNF gene and susceptibility to drug dependence. However, the
      pattern of results is inconsistent. To precisely evaluate this association, a
      systematic review and meta-analysis of previous case-control reports was
      conducted. Data from 20 studies containing 9419 participants (4665 cases and 4754
      controls) conducted between 2004 and 2013 restricted to alcohol, nicotine,
      heroin, substance and methamphetamine dependency were meta-analyzed. Following
      quality control of the results, a significant association between C allele and
      methamphetamine dependence remained in south Asian subjects (p = 0.004). Similar
      results were detected in south Asian subjects for methamphetamine dependence and
      in Chinese subjects for heroin dependence under an autosomal codominant genotype
      model (TT vs CC, p = 0.005 and p = 0.0004, respectively). In conclusion, the
      rs6265 polymorphism may be a risk factor for methamphetamine dependence in south
      Asian subjects or for heroin dependence in Chinese subjects. 

PMID- 24279860
TI  - Genetics of antipsychotic-induced weight gain: update and current perspectives.
AB  - Antipsychotic medications are used to effectively treat various symptoms for
      different psychiatric conditions. Unfortunately, antipsychotic-induced weight
      gain (AIWG) is a common side effect that frequently results in obesity and
      secondary medical conditions. Twin and sibling studies have indicated that
      genetic factors are likely to be highly involved in AIWG. Over recent years,
      there has been considerable progress in this area, with several consistently
      replicated findings, as well as the identification of new genes and implicated
      pathways. Here, we will review the most recent genetic studies related to AIWG
      using the Medline database (PubMed) and Google Scholar. Among the steadiest
      findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin
      promoter gene variants, with more recent studies implicating MTHFR and, in
      particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY,
      CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to
      have relatively large effect sizes. These findings have provided insights into
      the mechanisms involved in AIWG and will help to develop predictive genetic tests
      in the near future. 

PMID- 24279862
TI  - Cystatin C identifies cardiovascular risk better than creatinine-based estimates
      of glomerular filtration in middle-aged individuals without a history of
      cardiovascular disease.
AB  - OBJECTIVES: Creatinine- and cystatin C-based estimates of renal function are
      considered to be cardiovascular disease (CVD) risk factors, but the clinical
      utility in middle-aged subjects without a history of CVD is controversial.
      DESIGN: We related plasma cystatin C and creatinine-based glomerular filtration
      rate (GFR) [MDRD, CKD-EPI-2009, and CKD-EPI-comb (a combination of creatinine and
      cystatin C)] to incident CVD, CVD mortality, all-cause mortality, and heart
      failure in 4650 middle-aged subjects without CVD. RESULTS: The hazard ratio (HR)
      per standard deviation increment (95% CI) of cystatin C predicted incident CVD
      (1.22, 1.11-1.33; P < 0.0001), CVD mortality (1.44, 1.24-1.66; P < 0.0001), all
      cause mortality (1.15, 1.05-1.26; P = 0.002), and heart failure (1.27, 1.05-1.55;
      P = 0.02), whereas MDRD and CKD-EPI-2009 only predicted CVD mortality (0.79, 0.66
      0.93; P = 0.006 and 0.78, 0.66-0.92; P = 0.003, respectively). Cystatin C led to
      a significant increase in the net reclassification improvement for all endpoints,
      except heart failure. Only within the quartile with the worst renal function were
      all measures related to all-cause and CVD mortality. The top 25% of cystatin C in
      the population significantly predicted risk of incident CVD and CVD mortality,
      whereas MDRD and CKD-EPI-2009 were predictors of CVD mortality only at a GFR < 60
      mL/min/1.73 m(2) (11-13% of the population) and of incident CVD only at a GFR <
      45 mL/min/1.73 m(2) (<1% of the population). CONCLUSION: Cystatin C is a better
      risk marker for CVD morbidity and mortality than creatinine-based GFR. Whether
      this is explained by cystatin C being a better marker for true GFR or through
      other effects of cystatin C remains to be shown.

PMID- 24279863
TI  - Synergistic effects of nanoparticles and polymers on depletion and structural
      interactions.
AB  - An experimental study was performed to investigate the synergistic effects of two
      different solution components on the depletion and structural forces between
      colloidal particles. Using silica nanoparticles and anionic poly(acrylic acid)
      polymer, it was found that the depletion and structural forces measured between a
      30 MUm diameter silica sphere and a flat silica plate (obtained using colloidal
      probe atomic force microscopy) were substantially greater than the sum of the
      forces obtained in systems containing only nanoparticles and only polymer. This
      result arises because the anionic polymer chains adsorb to the nanoparticles,
      creating a complex that is over twice as large as either component. Although the
      number density of depletants decreases with such complexation, the larger size
      results in much greater forces at longer ranges. In addition, the measured force
      profiles could be well described using a force model in which all components were
      treated as hard, charged spheres. The results clearly indicate that predicting
      the depletion force in systems with multiple depletant components, such as the
      one used here, can be much more complicated than simply adding the forces
      contributed from each component independently. 

PMID- 24279864
TI  - Ligand noninnocence of thiolate/disulfide in dinuclear copper complexes: solvent
      dependent redox isomerization and proton-coupled electron transfer.
AB  - Copper thiolate/disulfide interconversions are related to the functions of
      several important proteins such as human Sco1, Cu-Zn superoxide dismutase (SOD1),
      and mammalian zinc-bonded metallothionein. The synthesis and characterization of
      well-defined synthetic analogues for such interconversions are challenging yet
      provide important insights into the mechanisms of such redox processes. Solvent
      dependent redox isomerization and proton-coupled electron transfer mimicking
      these interconversions are observed in two structurally related dimeric
      MU,eta(2):eta(2)-thiolato Cu(II)Cu(II) complexes by various methods, including X
      ray diffraction, XAS, NMR, and UV-vis. Spectroscopic evidence shows that a
      solvent-dependent equilibrium exists between the dimeric MU-thiolato Cu(II)Cu(II)
      state and its redox isomeric MU-disulfido Cu(I)Cu(I) form. Complete formation of
      MU-disulfido Cu(I)Cu(I) complexes, however, only occurs after the addition of 2
      equiv of protons, which promote electron transfer from thiolate to Cu(II) and
      formation of disulfide and Cu(I) via protonation of the coordinating ligand.
      Proton removal reverses this reaction. The reported unusual reductive
      protonation/oxidative deprotonation of the metal centers may serve as a new
      chemical precedent for how related proteins manage Cu ions in living organisms. 

PMID- 24279865
TI  - Health-related quality of life in patients with moderate to severe chronic
      obstructive pulmonary disease: a concept analysis.
AB  - AIM: The purpose of this concept analysis is to examine the health-related
      quality of life in patients with moderate to severe chronic obstructive pulmonary
      disease (COPD). BACKGROUND: COPD is the third leading cause of death in the
      United States. Health-related quality of life (HRQoL) in patients with moderate
      to severe COPD has not been clearly defined. DESIGN: Walker and Avant's concept
      analysis methodology was employed. REVIEW METHODS: The author examined articles
      focusing on QoL, HRQoL, and HRQoL in COPD. RESULTS: The concept analysis explores
      the negative consequences related to COPD while defining HRQoL and the
      characteristics of positive HRQoL. CONCLUSION: Patients living with COPD should
      be assessed for HRQoL status.

PMID- 24279866
TI  - The effect of topical ophthalmic 1% atropine on heart rate and rhythm in normal
      dogs.
AB  - OBJECTIVE: To determine if topically administered ophthalmic atropine affects
      heart rate or rhythm in clinically normal dogs. METHODS: Two groups of 15 healthy
      dogs were evaluated, one consisting of dogs weighing <15 kg, the other consisting
      of dogs weighing >15 kg. Each dog was suited with a Holter monitor. At start time
      0, dogs received one drop of ophthalmic 1% atropine solution, or one drop of
      sterile saline solution as a control in each eye, via random assignment. Each dog
      served as their own control. This procedure was repeated two more times, at 6-h
      intervals, for a total of three treatments over a 12-h period. Holter monitors
      recorded heart rate and rhythm for 24 h. Statistical analysis was performed to
      compare values between the groups. Dose dependent changes in cardiac parameters
      were evaluated. RESULTS: The mean heart rate and average minimum heart rate was
      significantly higher during the treatment period compared to the control period
      (8% and 13%, respectively). The mean number of hours with a heart rate <50 bpm
      decreased by 47% in the treatment vs. the control period. The mean maximum heart
      rate and number of h with a heart rate > 180 bpm did not differ significantly
      between the two groups. There was no evidence of dose dependence on heart rate
      when comparing small and large dogs. No significant differences in heart rhythm
      were noted between groups for measurable parameters. CONCLUSIONS: Topically
      administered atropine causes a small but significant increase in heart rate in
      healthy dogs.

PMID- 24279867
TI  - Atmospheric oxidation of peroxyacetic acid.
AB  - The full reactive atmospheric oxidation profile of peroxyacetic acid under high
      NO conditions was examined using electronic structure calculations at various
      levels of theory. The three pathways resulting from the reaction of peroxyacetic
      acid with the hydroxyl radical were (1) addition of OH to the central carbon, (2)
      abstraction of the acidic hydrogen, and (3) abstraction of the methyl hydrogen.
      These pathways were followed to terminal product steps, the major products being
      acetic acid for pathway 1 and formaldehyde for pathways 2 and 3. 

PMID- 24279869
TI  - Extending animal models to explore social rewards associated with designated
      smoking areas on college campuses.
AB  - OBJECTIVE: Animal studies have shown that when nicotine is administered in the
      presence of other animals (as compared with alone), it is more rewarding. As a
      human analogue to these studies, rewards associated with designated smoking areas
      on university campuses were examined, since these areas promote using nicotine in
      the presence of others. PARTICIPANTS: Participants were 118 (Sample 1, collected
      November 2011) and 94 (Sample 2, collected April 2012) student smokers at a
      midwestern university. METHOD: Data were collected via an Internet survey.
      RESULTS: Social interaction while smoking on campus (as compared with smoking
      alone) significantly increased the perceived reward of smoking, looking forward
      to spending time in the campus smoking areas, and how many times the campus
      smoking areas were visited. CONCLUSIONS: Although designated smoking areas may
      protect nonsmoking students from the dangers of secondhand smoke, these areas may
      increase the rewards associated with nicotine for the smokers who use them.

PMID- 24279868
TI  - Human induced pluripotent stem cell-derived mesenchymal stem cell seeding on
      calcium phosphate scaffold for bone regeneration.
AB  - Tissue engineering provides an important approach for bone regeneration. Calcium
      phosphate cement (CPC) can be injected to fill complex-shaped bone defects with
      excellent osteoconductivity. Induced pluripotent stem cells (iPSCs) are exciting
      for regenerative medicine due to their potential to proliferate and differentiate
      into cells of all three germ layers. To date, there has been no report on iPSC
      seeding with CPC scaffolds. The objectives of this study were to (1) obtain iPSC
      derived mesenchymal stem cells (iPSC-MSCs); (2) seed iPSC-MSCs on CPC scaffold
      for the first time to investigate cell attachment and proliferation; and (3)
      investigate osteogenic differentiation of iPSC-MSCs on CPC and mineral synthesis
      by the cells. iPSCs were derived from adult marrow CD34+ cells that were
      reprogrammed by a single episomal vector pEB-C5. iPSCs were cultured to form
      embryoid bodies (EBs), and MSCs were migrated out of EBs. Flow cytometry
      indicated that iPSC-MSCs expressed typical surface antigen profile of MSCs.
      Mesenchymal differentiation of iPSC-MSCs demonstrated that the iPSC-MSCs had the
      potential to differentiate into adipocytes, chondrocytes, and osteoblasts. iPSC
      MSCs had good viability when attached on CPC scaffold. iPSC-MSCs differentiated
      into the osteogenic lineage and synthesized bone minerals. iPSC-MSCs on CPC in
      osteogenic medium yielded higher gene expressions of osteogenic markers including
      alkaline phosphatase (ALP), osteocalcin, collagen type I, and Runt-related
      transcription factor 2 than those in control medium (p<0.05). iPSC-MSCs on CPC in
      osteogenic medium had 10-fold increase in ALP protein than that in control medium
      (p<0.05). Bone mineral synthesis by iPSC-MSCs adherent to CPC scaffold was
      increased with time, and mineralization in osteogenic medium was three to four
      fold that in control medium. In conclusion, iPSCs were derived from adult marrow
      CD34+ cells that were reprogrammed by a single episomal vector pEB-C5, and MSCs
      were generated from the EBs. iPSC-MSCs showed good viability and osteogenic
      differentiation on CPC scaffold for the first time; hence, the novel iPSC-MSC-CPC
      construct is promising to promote bone regeneration in dental, craniofacial, and
      orthopedic repairs.

PMID- 24279870
TI  - Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like
      syndrome in rats.
AB  - Abstinence from chronic ethanol consumption leads to the manifestation of a
      variety of symptoms attributed to central nervous system hyperexcitability, such
      as increased irritability, anxiety, and restlessness. Recent studies have
      demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in
      addictive behaviours. This study investigates the effects of the mGluR5
      antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal
      induced anxiety using two behavioural paradigms. Male Wistar rats were fed a
      Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin
      with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours
      into ethanol withdrawal, the rats were intraperitoneally injected with normal
      saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol
      withdrawal induced anxiety-like syndrome using an automated elevated plus maze
      and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal
      induced anxiety without any compromising effects on locomotor activities. Despite
      reversing several indices of ethanol withdrawal induced anxiety in both the
      elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg)
      significantly compromised the locomotor activities of ethanol withdrawn rats.
      High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety
      when tested in the elevated plus maze but not in the open field. Administration
      of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the
      locomotor activities of ethanol naive rats. Despite significantly reducing
      withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising
      effects of low and high doses of MPEP must be further explored along with the
      therapeutic efficiency of this drug for relieving withdrawal induced anxiety. 

PMID- 24279872
TI  - Development of antibacterial and antifungal silver-coated polyurethane foams as
      air filtration units for the prevention of respiratory diseases.
AB  - AIM: The development of silver-coated polyurethane filters as filtration units
      for the prevention of the respiratory diseases. METHODS AND RESULTS: An
      innovative silver deposition technology based on the photo-reduction in a silver
      salt was adopted. The efficacy of the technology in providing a homogeneous
      distribution of the silver particles was verified by scanning electron microscopy
      and energy dispersive X-ray spectroscopy. The materials were tested through
      microbiological procedures used in industry to verify the efficacy of the silver
      coated filters on the viability and growth of selected micro-organisms. Direct
      inoculation test, filtration experiment and shaking tests were performed on
      microbial human pathogens associated with air filtration units and respiratory
      disease, namely Legionella pneumophila, Pseudomonas aeruginosa, Aspergillus niger
      and Aspergillus flavus, by adopting Escherichia coli and Staphylococcus aureus as
      control organisms. CONCLUSIONS: The results provided evidence of the
      effectiveness of the silver coating in reducing the bioaerosolization of viable
      human pathogens into environments using recirculated air. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Micro-organisms can affect the air quality in indoor environments
      and can be responsible for infectious, allergic or toxic disturbances on human
      airways. The development of an adequate bioaerosol control might ameliorate a
      positive health effect in humans.

PMID- 24279871
TI  - G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of
      CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses.
AB  - BACKGROUND: Administration of recombinant G-CSF following cytoreductive therapy
      enhances the recovery of myeloid cells, minimizing the risk of opportunistic
      infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has
      poor biological activity in vivo. METHODS: We evaluated whether the biological
      activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior
      to injection into mice. RESULTS: We find that the efficacy of G-CSF therapy can
      be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF
      monoclonal antibody (mAb). Compared with G-CSF alone, administration of G
      CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid
      cells in mice with or without concomitant cytoreductive treatment including
      radiation or chemotherapy. Despite driving the dramatic expansion of myeloid
      cells, in vivo antigen-specific CD8+ T cell immune responses were not
      compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened
      protective immunity to bacterial infection. As a measure of clinical value, we
      also found that antibody complexes improved G-CSF biological activity much more
      significantly than pegylation. CONCLUSIONS: Our findings provide the first
      evidence that antibody cytokine complexes can effectively expand myeloid cells,
      and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved
      method for the administration of recombinant G-CSF.

PMID- 24279873
TI  - Prevalence of asthmatic smokers: Turkish experience (PASTE Study).
AB  - BACKGROUND: Although both asthma and smoking are major health problems worldwide,
      smokers are often excluded from asthma studies. OBJECTIVES: It was aimed to
      verify the prevalence of asthmatic smokers in Turkey and assess the effects of
      smoking based on clinical parameters, exacerbations and hospitalizations because
      of lack of national data about the prevalence of smoking among asthmatics.
      METHODS: The study protocol was comprised of a retrospective questionnaire. The
      asthmatic patients were followed in the outpatient clinics of 18 tertiary
      hospitals selected from seven different geographical regions in Turkey. We
      evaluated demographic data, smoking habits, asthma-related diseases, respiratory
      function and emergency visits. RESULTS: The study population included 1385
      patients (M/F: 343/1042), and the mean age was 45.1 +/- 14.0 years. Current and
      former smoking prevalence was 11.4% and 15.1%, respectively. Smoker rates were
      higher in males and younger asthmatics compared with females and older asthmatics
      (P < 0.01 and P < 0.05, respectively). Smoking history ranged from 0.20 to 90
      pack-years (the mean was 12.9), and smokers had a higher level of education
      compared with nonsmokers (P < 0.01). Socioeconomically, the most developed region
      had the highest rate of smoker asthmatics (33.9%; P = 0.014). There was an
      increase in the number of exacerbations in smoker asthmatics during the previous
      year, but it was not statistically significant (P > 0.05). CONCLUSION: We showed
      that the smoking prevalence in Turkey was lower in asthmatics (11.4%) compared
      with the general population (44.5%). Nevertheless, every effort should be made to
      encourage asthmatics to stop smoking because smoking is a modifiable risk factor
      for adverse asthma health outcomes.

PMID- 24279874
TI  - Assessment of resource use and costs associated with parathyroidectomy for
      secondary hyperparathyroidism in end stage renal disease in the UK.
AB  - INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a major complication of end
      stage renal disease (ESRD). For the National Health Service (NHS) to make
      appropriate choices between medical and surgical management, it needs to
      understand the cost implications of each. A recent pilot study suggested that the
      current NHS healthcare resource group tariff for parathyroidectomy (PTX) (L2071
      and L1859 in patients with and without complications, respectively) is not
      representative of the true costs of surgery in patients with SHPT. OBJECTIVE:
      This study aims to provide an estimate of healthcare resources used to manage
      patients and estimate the cost of PTX in a UK tertiary care centre. METHODS:
      Resource use was identified by combining data from the Proton renal database and
      routine hospital data for adults undergoing PTX for SHPT at the University
      Hospital of Wales, Cardiff, from 2000-2008. Data were supplemented by a
      questionnaire, completed by clinicians in six centres across the UK. Costs were
      obtained from NHS reference costs, British National Formulary and published
      literature. Costs were applied for the pre-surgical, surgical, peri-surgical, and
      post-surgical periods so as to calculate the total cost associated with PTX.
      RESULTS: One hundred and twenty-four patients (mean age=51.0 years) were
      identified in the database and 79 from the questionnaires. The main costs
      identified in the database were the surgical stay (mean=L4066, SD=L,130), the
      first month post-discharge (L465, SD=L176), and 3 months prior to surgery (L399,
      SD=L188); the average total cost was L4932 (SD=L4129). From the questionnaires
      the total cost was L5459 (SD=L943). It is possible that the study was limited due
      to missing data within the database, as well as the possibility of recall bias
      associated with the clinicians completing the questionnaires. CONCLUSION: This
      analysis suggests that the costs associated with PTX in SHPT exceed the current
      NHS tariffs for PTX. The cost implications associated with PTX need to be
      considered in the context of clinical assessment and decision-making, but
      healthcare policy and planning may warrant review in the light of these results.

PMID- 24279875
TI  - Effects of different Fe supplies on mineral partitioning and remobilization
      during the reproductive development of rice (Oryza sativa L.).
AB  - BACKGROUND: Minimal information exists on whole-plant dynamics of mineral flow
      through rice plants and on the source tissues responsible for mineral export to
      developing seeds. Understanding these phenomena in a model plant could help in
      the development of nutritionally enhanced crop cultivars. A whole-plant
      accumulation study, using harvests during reproductive development under
      different Fe supplies, was conducted to characterize mineral accumulation in
      roots, non-flag leaves, flag leaves, stems/sheaths, and panicles of Kitaake rice
      plants. RESULTS: Low Fe supply promoted higher accumulation of Zn, Cu and Ni in
      roots, Mn, Ca, Mg and K in leaves and Zn in stems/sheaths and a smaller
      accumulation of Fe, Mn and Ca in roots and Zn and Ni in leaves. High Fe supply
      promoted higher accumulation of Fe in roots and Zn in leaves and a smaller
      accumulation of Fe in leaves and stems/sheaths and Zn, Cu and K in roots.
      Correlation analyzes indicated that fluctuations in Mn-Ca, Zn-Cu, Zn-Ni, Cu-Ni,
      Mo-S, Ca-Mg, Cu-Mn and Cu-Mg concentrations in response to different Fe supplies
      were positively correlated in at least four of the five organs analyzed.
      CONCLUSIONS: Mineral content loss analysis indicated that mineral remobilization
      from vegetative organs can occur in rice plants; however, for seeds to acquire
      minerals, vegetative remobilization is not absolutely required. Also, mineral
      remobilization from vegetative tissues in rice was greatly dependent of plant Fe
      nutrition. Remobilization was observed for several minerals from flag leaves and
      stems/sheaths, but the amounts were generally far below the total mineral
      accretion observed in panicles, suggesting that continued uptake and
      translocation of minerals from the roots during seed fill are probably more
      important than mineral remobilization.

PMID- 24279876
TI  - Heart and combined heart-kidney transplantation in patients with concomitant
      renal insufficiency and end-stage heart failure.
AB  - In patients with end-stage heart failure (ESHF) who are candidates for isolated
      heart transplant (HRT), dialysis dependence (DD) is considered an indication for
      combined heart-kidney transplantation (HKT). HKT remains controversial in ESHF
      transplant candidates with nondialysis-dependent renal insufficiency (NDDRI).
      Using United Network for Organ Sharing data, we examined the cumulative
      incidences of transplant and mortality in patients with DD and NDDRI waitlisted
      for HKT or HRT. In all groups, 3-month waitlist mortality was dismal: 31% and 21%
      for HRT- and HKT-listed patients with DD and 12% and 7% for HRT- and HKT-listed
      patients with NDDRI. Five-year posttransplant survival was improved in HKT
      recipients compared with HRT recipients for both patients with DD (73% vs. 51%,
      p<0.001) and NDDRI (80% vs. 69%, p<0.001). Likewise, multivariable analysis
      associated HKT with better outcomes than HRT in HKT-listed patients, although
      both improved survival. These data argue strongly for HKT in ESHF transplant
      candidates with DD. However, in patients with NDDRI, HKT must be weighed against
      the possibility of renal recovery with isolated HRT. Whether HRT (followed by a
      staged kidney transplant in patients who do not recover renal function after
      HRT), as opposed to HKT, maximizes organ benefit for patients with NDDRI and ESHF
      requires assessment. Nevertheless, given their dismal waitlist outcomes and
      excellent posttransplant results, we suggest that patients with DD and NDDRI with
      ESHF be considered for early listing and transplant.

PMID- 24279878
TI  - Diindole-annulated naphthalene diimides: synthesis and optical and electronic
      properties of syn- and anti-isomers.
AB  - Here we report a selective method for the core-extension of naphthalene diimide
      (NDI) with two annulated indole rings leading to carbazolo[2,3-b]carbazole
      diimides (CbDIs) with exclusive syn-connectivity based on a regioselective
      nucleophilic substitution reaction of Br4-NDI with arylamines, followed by
      palladium-catalyzed intramolecular C-C coupling. The oxygen analogues of anti
      CbDIs, namely anti-benzofurobenzofuran diimides (anti-BfDIs), were obtained from
      2,6-Br2-NDI and 2-bromophenol. The syn- and anti-isomers of CbDIs were
      unambiguously characterized by single-crystal X-ray analysis. The optical
      properties of the present core-enlarged NDIs were studied, revealing clear
      differences in the absorption characteristics of the syn- and anti-isomers of
      CbDI, on one hand, and CbDI vs BfDI derivatives, on the other hand. Cyclic
      voltammetry studies showed that the redox properties are dependent on the
      substituents at the CbDI-core and oxygen atom containing BfDIs are more prone to
      reduction than the respective nitrogen analogues CbDIs. Vacuum-processed organic
      field effect transistors reveal CbDI and BfDI derivatives with n-channel, p
      channel, as well as ambient transport characteristics with mobility values up to
      0.2 cm(2)/(V s). 

PMID- 24279877
TI  - Thrombin increases lung fibroblast survival while promoting alveolar epithelial
      cell apoptosis via the endoplasmic reticulum stress marker, CCAAT enhancer
      binding homologous protein.
AB  - Apoptosis of alveolar epithelial cells (AECs) and survival of lung fibroblasts
      are critical events in the pathogenesis of pulmonary fibrosis; however,
      mechanisms underlying the apoptosis of AECs and the resistance of lung
      fibroblasts to apoptosis remain obscure. Herein, we demonstrate that the fate of
      these two cell types depends on the expression of CCAAT enhancer-binding
      homologous protein (CHOP). We observed that thrombin, which is overexpressed in
      scleroderma (SSc; systemic sclerosis) and other interstitial lung diseases
      (ILDs), increases the expression of CHOP in primary AECs and in A549 cells via an
      Ets1-dependent pathway. In addition, thrombin activates caspase-3 in AECs and
      induces apoptosis of these cells in a CHOP-dependent manner. In contrast,
      thrombin decreases endoplasmic reticulum stress-induced CHOP in lung fibroblasts
      through Myc-dependent mechanisms and protects such cells from apoptosis.
      Furthermore, when lung fibroblasts are transfected with recombinant CHOP, they
      then undergo apoptosis, even in the presence of thrombin, suggesting that CHOP
      signaling pathways are downstream of thrombin. In accordance with the
      differential effects of thrombin on AECs and lung fibroblasts, we observed strong
      expression of CHOP in AECs in fibrotic lung tissue isolated from patients with
      SSc-associated ILD (SSc-ILD), but not in lung myofibroblasts nor in normal lung
      tissue. Expression of CHOP in SSc lung is accompanied by positive staining for
      the thrombin receptor, protease-activated receptor-1, and for terminal
      deoxynucleotidyl transferase dUTP nick end labeling, suggesting roles for both
      thrombin and CHOP in AEC apoptosis in SSc-ILD. We conclude that regulation of
      CHOP by thrombin directs AECs toward apoptosis while promoting survival of lung
      fibroblasts, ultimately contributing to the persistent fibroproliferation seen in
      SSc-ILD and other fibrosing lung diseases.

PMID- 24279879
TI  - Secondary interventions after endovascular thoracic aortic repair.
AB  - BACKGROUND: Endovascular stent grafting of the descending thoracic aorta has
      evolved rapidly and is now the standard of care for certain patient subsets.
      However, the durability of this technique is limited by the development of
      technique-specific complications at mid-term follow-up. The aim of this study was
      to evaluate the incidence, techniques, and outcomes of secondary intervention for
      complications after stent grafting of the descending thoracic aorta. METHODS:
      Between March 2001 and November 2011, 152 patients underwent endovascular
      thoracic aortic repair (TEVAR). We identified 19 (12.5%) patients from this
      cohort who required secondary interventions. RESULTS: The indications for TEVAR
      were type B aortic dissection in 12 patients, thoracic aortic aneurysm in six
      patients, and intramural hematoma in one patient. The mean time between TEVAR and
      secondary intervention was 20.49 +/- 24.90 months (range, 1.2-83 months). A
      secondary endovascular intervention was required in eleven patient, six patients
      required secondary surgical therapy, and hybrid procedures were performed in two
      patients. Endoleaks were the most common indication for a secondary intervention.
      The 30-day mortality rate was 10.5% (2/19). Two perioperative deaths were
      observed following surgical therapy. During the mean follow-up of 78.06 +/- 37.37
      months (range, 23-142 months) after TEVAR, four unrelated deaths occurred, two
      patients were lost to follow-up, and four patients required a further
      intervention. CONCLUSIONS: Secondary intervention after endovascular stent
      grafting of the descending thoracic aorta was not infrequently required and can
      be performed with acceptable risks. However, serial, systematic follow-up is
      essential to detect late complications and to perform secondary procedures,
      preferably under elective circumstances.

PMID- 24279880
TI  - Sol-gel-derived materials for production of pin-printed reporter gene living-cell
      microarrays.
AB  - We report the fabrication of three-dimensional living-cell microarrays via pin
      printing of soft sol-gel-derived silica materials containing bacterial cells.
      Bacterial cells entrapped in the silica-glycerol microarray spots can express
      reporter genes and produce strong fluorescence signals. The signals responded to
      the presence and concentration of inducers or repressors as expected, indicating
      that the entrapped cells remained metabolically active. Microscopic imaging of
      individual microarray spots at different culture times suggests that the
      entrapped cells can grow and divide, phenomena further confirmed by experiments
      in bulk sol-gel materials that demonstrated the increases of entrapped cell
      density and fluorescence during incubation in culture media. The cell microarrays
      can also be printed into 96-well glass bottom microtiter plates in a multiplexed
      manner, and the fluorescence signals generated were able to quantitatively and
      selectively respond to the concentration of inducers, thus demonstrating the
      potential for multitarget biosensing and high-throughput/high-content cell-based
      screening. The signal levels of bacterial cells in silica were significantly
      higher than those in alginate arrays, presumably due to viability of the
      entrapped cells in silica sol-gels. Microarray stability assays proved that the
      entrapped cells retained their physiological activity after storage for four
      weeks. Given that a large number of fluorescent and luminescent protein-based
      cell assays have been developed, the reporter gene living-cell microarrays
      demonstrated in this paper are expected to be applicable to a wide variety of
      research areas ranging from bioanalysis and chemical biology to drug discovery
      and probing of cell-material interactions. 

PMID- 24279881
TI  - An in planta, Agrobacterium-mediated transient gene expression method for
      inducing gene silencing in rice (Oryza sativa L.) leaves.
AB  - BACKGROUND: Localized introduction and transient expression of T-DNA constructs
      mediated by agro-infiltration of leaf tissues has been largely used in dicot
      plants for analyzing the transitivity and the cell-to cell movement of the RNAi
      signal. In cereals, however, the morphology of the leaf and particularly the
      structure of the leaf epidermis, prevent infiltration of a bacterial suspension
      in cells by simple pressure, a method otherwise successful in dicots leaves. This
      study aimed at establishing a rapid method for the functional analysis of rice
      genes based on the triggering of RNA interference (RNAi) following Agrobacterium
      mediated transient transformation of leaves. RESULTS: Using an agro-infection
      protocol combining a wound treatment and a surfactant, we were able to obtain in
      a reliable manner transient expression of a T-DNA-borne uidA gene in leaf cells
      of japonica and indica rice cultivars. Using this protocol to transiently inhibit
      gene expression in leaf cells, we introduced hairpin RNA (hpRNA) T-DNA constructs
      containing gene specific tags of the phytoene desaturase (OsPDS) and of the
      SLENDER 1 (OsSLR1) genes previously proven to trigger RNAi of target genes in
      stable transformants. SiRNA accumulation was observed in the agro-infected leaf
      area for both constructs indicating successful triggering of the silencing
      signal. Accumulation of secondary siRNA was observed in both stably and
      transiently transformed leaf tissues expressing the HpRNA OsSLR1 construct. Gene
      silencing signalling was investigated in monitoring the parallel time course of
      OsPDS-derived mRNA and siRNA accumulation in the agro-infiltrated leaf area and
      adjacent systemic sectors. The sensitive RT-Q-PCR method evidenced a consistent,
      parallel decrease of OsPDS transcripts in both the agroinfiltred and adjacent
      tissues, with a time lag for the latter. CONCLUSIONS: These results indicate that
      the method is efficient at inducing gene silencing in the agro-infected leaf
      area. The transfer of low amounts of siRNA, probably occurring passively through
      the symplastic pathway from the agro-infected area, seemed sufficient to trigger
      degradation of target transcripts in the adjacent tissues. This method is
      therefore well suited to study the cell-to-cell movement of the silencing signal
      in a monocot plant and further test the functionality of natural and artificial
      miRNA expression constructs.

PMID- 24279883
TI  - An assessment of powder pycnometry as a means of determining granule porosity.
AB  - A powder pycnometry method, using a commercially available instrument (GeoPyc(r)
      with DryFlo(r) displacement media), was evaluated as a means of measuring the
      envelope density of hydroxyapatite (HA) granules in the size range of 75-8000 um.
      The aims of this study were to (1) investigate the reproducibility of the
      DryFlo(r) powder particle size and consolidation properties, (2) determine the
      number of preparation cycles required before test measurements should be taken,
      (3) compare the powder pycnometry method to the reference mercury porosimetry
      method and (4) investigate the effect of granule size on envelope density
      measurement. DryFlo(r) was shown to have a reproducible particle size when
      sampled at multiple locations across three separate containers. A minimum of 1
      preparation cycle should be used to ensure consistent packing of the DryFlo(r)
      and HA granules. DryFlo(r) density was found to be insensitive to consolidation
      forces in the range of 10-100 N. The powder pycnometry method could be linearly
      calibrated against the reference mercury porosimetry method when considering
      polydisperse HA granule samples. However, when analyzing narrow particle size
      fractions limitations in the powder pycnometry method were noted resulting in a
      reduced particle size range of 1850-4050 um that could be linearly calibrated
      against the mercury porosimetry method. 

PMID- 24279882
TI  - Innate immune response precedes Mycobacterium leprae-induced reprogramming of
      adult Schwann cells.
AB  - Recently, we showed a natural reprogramming process during infection with
      Mycobacterium leprae (ML), the causative organism of human leprosy. ML hijacks
      the notable plasticity of adult Schwann cells in the peripheral nervous system
      (PNS), bacteria's preferred nonimmune niche, to reprogram infected cells to
      progenitor/stem cell-like cells (pSLCs). Whereas ML appear to use this
      reprogramming process as a sophisticated bacterial strategy to spread infection
      to other tissues, understanding the mechanisms may shed new insights into the
      basic biology of cellular reprogramming and the development of new approaches for
      generating pSLC for therapeutic purposes as well as targeting bacterial
      infectious diseases at an early stage. Toward these goals, we extended our
      studies to identify other players that might be involved in this complex host
      cell reprogramming. Here we show that ML activates numerous immune-related genes
      mainly involved in innate immune responses and inflammation during early
      infection before downregulating Schwann cell lineage genes and reactivating
      developmental transcription factors. We validated these findings by demonstrating
      the ability of infected cells to secrete soluble immune factor proteins at early
      time points and their continued release during the course of reprogramming. By
      using time-lapse microscopy and a migration assay with reprogrammed Schwann cells
      (pSLCs) cultured with macrophages, we show that reprogrammed cells possess the
      ability to attract macrophages, providing evidence for a functional role of
      immune gene products during reprogramming. These findings suggest a potential
      role of innate immune response and the related signaling pathways in cellular
      reprogramming and the initiation of neuropathogenesis during ML infection.

PMID- 24279884
TI  - Formation of the high-affinity calcium binding site in pro-subtilisin E with the
      insertion sequence IS1 of pro-Tk-subtilisin.
AB  - Subtilisin E is activated from its inactive precursor Pro-subtilisin E by
      autoprocessing and degradation of the propeptide. Subtilisin E has two calcium
      binding sites, the high-affinity Ca1 site and the low-affinity Ca2 site. The Ca1
      site is conserved in various subtilisin-like proteases and is important for
      stability. This site is not formed in Pro-subtilisin E, because the structural
      rearrangement of the N-terminal region of the subtilisin domain upon
      autoprocessing is necessary for the formation of this site. As a result, Pro
      subtilisin E is not fully folded. In contrast, Pro-Tk-subtilisin from
      Thermococcus kodakarensis is fully folded, because it does not require the
      structural rearrangement upon autoprocessing for the formation of the Ca1 site
      due to the presence of the insertion sequence IS1 between the propeptide and
      subtilisin domains. To examine whether the Ca1 site is formed in Pro-subtilisin E
      by inserting IS1 between the propeptide and subtilisin domains, the Pro
      subtilisin E mutant with this insertion, IS1-Pro-subtilisin E, and its active
      site mutants, IS1-Pro-S221A and IS1-Pro-S221C, were constructed and
      characterized. The crystal structure of IS1-Pro-S221A revealed that this protein
      is fully folded and the Ca1 site is formed. In this structure, IS1 serves as a
      linker that brings the N-terminus of the subtilisin domain near the Ca1 site. IS1
      Pro-S221A in a calcium-bound form was more stable than that in a calcium-free
      form by 13.1  degrees C. IS1-Pro-S221C was more rapidly autoprocessed than Pro
      S221C. These results suggest that IS1 facilitates the formation of the Ca1 site
      and the complete folding of Pro-subtilisin E and thereby accelerates its
      autoprocessing. 

PMID- 24279885
TI  - Use of ultrasonic spectroscopy and viscosimetry for the characterization of
      chicken skin collagen in comparison with collagens from other animal tissues.
AB  - Use of traditional sources of collagen such as pork, bovine, and carp has some
      limitations. Chicken skin can be valuable alternative. In this work collagen was
      isolated from chicken skin using a modified procedure. Molecular properties of
      chicken collagen were analyzed and compared to collagen from other animal skins.
      Acid-soluble collagen type I was obtained with a yield of 25% and water content
      around 67%. Viscosimetry and ultrasonic spectroscopy were newly used for
      molecular characterization. By ultrasonic attenuation measurements, a pre
      aggregation phase in the interval from 20 degrees C to 27 degrees C was observed,
      which is a proof of disaggregation and liquefaction. From 40 degrees C upward,
      the liquefaction process finishes and aggregation continues. In a bovine sample
      this phenomenon starts at 40 degrees C, in chicken at 50 degrees C, and continues
      until 70 degrees C. By viscosimetry, the denaturation temperature was confirmed
      as 40 degrees C for bovine and 50 degrees C for chicken collagen. Chicken
      collagen has a two times higher lysine level than bovine, which provides
      molecular stability side-chain interactions. With regard to higher thermal
      stability and favorable amino acid composition, waste chicken skin has the
      potential to be an excellent alternative source of raw collagen with applications
      in the food industry and biomedicine. 

PMID- 24279886
TI  - Metabolic flux analysis using 13C peptide label measurements.
AB  - 13C metabolic flux analysis (MFA) has become the experimental method of choice to
      investigate the cellular metabolism of microbes, cell cultures and plant seeds.
      Conventional steady-state MFA utilizes isotopic labeling measurements of amino
      acids obtained from protein hydrolysates. To retain spatial information in
      conventional steady-state MFA, tissues or subcellular fractions must be dissected
      or biochemically purified. In contrast, peptides retain their identity in complex
      protein extracts, and may therefore be associated with a specific time of
      expression, tissue type and subcellular compartment. To enable 'single-sample'
      spatially and temporally resolved steady-state flux analysis, we investigated the
      suitability of peptide mass distributions (PMDs) as an alternative to amino acid
      label measurements. PMDs are the discrete convolution of the mass distributions
      of the constituent amino acids of a peptide. We investigated the requirements for
      the unique deconvolution of PMDs into amino acid mass distributions (AAMDs), the
      influence of peptide sequence length on parameter sensitivity, and how AAMD and
      flux estimates that are determined through deconvolution compare to estimates
      from a conventional GC-MS measurement-based approach. Deconvolution of PMDs of
      the storage protein beta-conglycinin of soybean (Glycine max) resulted in good
      AAMD and flux estimates if fluxes were directly fitted to PMDs. Unconstrained
      deconvolution resulted in inferior AAMD and flux estimates. PMD measurements do
      not include amino acid backbone fragments, which increase the information content
      in GC-MS-derived analyses. Nonetheless, the resulting flux maps were of
      comparable quality due to the precision of Orbitrap quantification and the larger
      number of peptide measurements.

PMID- 24279888
TI  - Nanorod niobium oxide as powerful catalysts for an all vanadium redox flow
      battery.
AB  - A powerful low-cost electrocatalyst, nanorod Nb2O5, is synthesized using the
      hydrothermal method with monoclinic phases and simultaneously deposited on the
      surface of a graphite felt (GF) electrode in an all vanadium flow battery (VRB).
      Cyclic voltammetry (CV) study confirmed that Nb2O5 has catalytic effects toward
      redox couples of V(II)/V(III) at the negative side and V(IV)/V(V) at the positive
      side to facilitate the electrochemical kinetics of the vanadium redox reactions.
      Because of poor conductivity of Nb2O5, the performance of the Nb2O5 loaded
      electrodes is strongly dependent on the nanosize and uniform distribution of
      catalysts on GF surfaces. Accordingly, an optimal amount of W-doped Nb2O5
      nanorods with minimum agglomeration and improved distribution on GF surfaces are
      established by adding water-soluble compounds containing tungsten (W) into the
      precursor solutions. The corresponding energy efficiency is enhanced by ~10.7% at
      high current density (150 mA.cm(-2)) as compared with one without catalysts. Flow
      battery cyclic performance also demonstrates the excellent stability of the as
      prepared Nb2O5 catalyst enhanced electrode. These results suggest that Nb2O5
      based nanorods, replacing expensive noble metals, uniformly decorating GFs holds
      great promise as high-performance electrodes for VRB applications. 

PMID- 24279887
TI  - Treated incidence and baseline characteristics of substance induced psychosis in
      a Norwegian catchment area.
AB  - BACKGROUND: Substance misuse is a well-recognized co-morbidity to psychosis and
      has been linked to poor prognostic outcomes in patients. Researchers have yet to
      investigate the difference in rates and characteristics between first-episode
      Substance Induced Psychosis (SIP) and primary psychosis. We aimed at comparing
      patients with SIP to primary psychosis patients with or without substance misuse
      at baseline. METHODS: Thirty SIP patients, 45 primary psychosis patients with
      substance misuse (PS) and 66 primary psychosis patients without substance misuse
      (PNS) in a well-defined Norwegian catchment area were included from 2007-2011.
      Assessments included symptom levels (PANSS), diagnostic interviews (SCID),
      premorbid function scale (PAS) and global functioning (GAF f/s). RESULTS: Treated
      incidence for SIP was found to be 6.5/100 000 persons per year, 9.7/100 000
      persons per year for PS and 24.1/100 000 persons per year for PNS (15-65 yrs).
      Patients who had substance misuse (PS and SIP) were more likely to be male.
      Duration of Untreated Psychosis (DUP) was significantly shorter in the SIP group
      (5.0 wks., p = 0.003) and these had more positive symptoms on the PANSS (p =
      0.049). SIP patients also did poorer on early youth academic levels on the PAS.
      CONCLUSIONS: Yearly treated incidence of SIP is 6.5/100 000 persons per year in a
      Norwegian catchment area. SIP patients have short DUPs, are more likely to be
      male, have more positive symptoms at baseline and poorer premorbid academic
      scores in early adolescence. Follow-up will evaluate stability of diagnosis and
      characteristics.

PMID- 24279889
TI  - Design and evaluation of a prelicensure interprofessional course on improving
      care transitions.
AB  - Effective management of care transitions for older adults require the coordinated
      expertise of an interprofessional team. Unfortunately, different health care
      professions are rarely educated together or trained in teamwork skills. To
      address this issue, a team of professionally diverse faculty from the Duke
      University Geriatric Education Center designed an interprofessional course
      focused on improving transitions of care for older adults. This innovative
      prelicensure course provided interactive teaching sessions designed to promote
      critical thinking and foster effective communication among health care
      professionals, caregivers, and patients. Students were assessed by in-class and
      online participation, performance on individual assignments, and team-based
      proposals to improve care transitions for older patients with congestive heart
      failure. Twenty students representing six professions completed the course; 18
      completed all self-efficacy and course evaluation surveys. Students rated their
      self-efficacy in several domains before and after the course and reported gains
      in teamwork skills (p < .001), transitions of care (p < .001), quality
      improvement (p < .001) and cultural competence (p < .001). Learner feedback
      emphasized the importance of enthusiastic and well-prepared faculty, interactive
      learning experiences, and engagement in relevant work. This course offers a
      promising approach to shifting the paradigm of health professions education to
      empower graduates to promote quality improvement through team-based care.

PMID- 24279890
TI  - Fungal infections associated with long-term mechanical circulatory support
      diagnosis and management.
AB  - Left ventricular assist devices (LVADs) are increasingly used as a treatment
      option for advanced heart failure. Fungal infections present a serious concern
      given the high association with major adverse events including death in this
      group of patients. The objective of this review is to summarize the incidence,
      risk factors, method for diagnosis, complication rate, and outcomes in patients
      with VADs who develop fungal infections.

PMID- 24279891
TI  - Stage-specific embryonic antigen 4 in Wharton's jelly-derived mesenchymal stem
      cells is not a marker for proliferation and multipotency.
AB  - BACKGROUND: Umbilical cord Wharton's jelly (WJ) is a rich source of mesenchymal
      stem cells (MSCs) similar to bone marrow (BM) and adipose tissues. Stage-specific
      embryonic antigen (SSEA)4 has been reported as a stem cell marker in BM-derived
      MSCs, but whether SSEA4(+) cells have growth and differentiation advantages over
      SSEA4(-) cells remains controversial. To gain insight into the role of SSEA4, we
      studied SSEA4(+) cells in WJ-derived MSCs (WJ-MSCs). METHODS: WJ-MSCs were
      collected by the explant (WJe-MSCs) or collagenase methods (WJc-MSCs) and
      analyzed by flow cytometry and reverse-transcription polymerase chain reaction
      (RT-PCR). To evaluate whether culture conditions influenced the SSEA4 expression,
      WJe-MSCs were cultured in the medium supplemented with different fetal bovine
      serum (FBS) concentrations. RESULTS: SSEA4 was expressed for a long-term culture.
      In contrast, SSEA3(+) disappeared rapidly in early passages of the culture. The
      incidence of SSEA4(+) and SSEA3(+) cells was similar between WJe-MSCs and WJc
      MSCs at passages P0-P9, except for transient depletion of SSEA4 expression in
      early passages of WJe-MSCs. These were CD73(+)CD105(+) cells that express
      embryonic stem cell markers detected by RT-PCR. No differences in growth and
      differentiation ability of osteocytes and adipocytes were observed between the
      sorted SSEA4(+) cells and SSEA4(-) cells. Further, SSEA4 expression in WJe-MSCs
      was significantly correlated with FBS concentration in the culture medium.
      DISCUSSION: SSEA4, which may display altered expression profiles in response to
      culture conditions, may not be an essential marker of WJ-MSC multipotency.

PMID- 24279892
TI  - The timing of pediatric epilepsy syndromes: what are the developmental triggers?
AB  - Pediatric epilepsy is characterized by multiple epilepsy syndromes with specific
      developmental triggers. They initiate spontaneously at critical periods of
      development and can just as spontaneously remit. Accompanying neurocognitive
      disabilities are often specific to the epileptic syndrome. Infantile or epileptic
      spasms have a very specific developmental window in the first year of life.
      Preceding the epilepsy, developmental arrest is common. The neurologic pathways
      underlying the development of spasms have been identified through PET scans as
      developmental abnormalities of serotonergic and GABAergic neurotransmitter
      systems in the brain stem and basal ganglia. Childhood absence epilepsy (CAE) and
      benign centrotemporal epilepsy syndrome (BECTS) are both known genetic epilepsy
      syndromes; they have a discrete onset in childhood with remission by puberty. In
      CAE, disturbances of specific calcium channels at key developmental stages lead
      to aberrant disruption of thalamocortical synchrony. Similarly, a complex
      interplay between brain development, maturation, and susceptibility genes
      underlies the seizures and the neurocognitive deficits of BECTS. 

PMID- 24279893
TI  - Treatment of pediatric anxiety disorders.
AB  - This article provides a brief review of the current available data concerning
      present treatment and potential new treatment advances for pediatric anxiety
      disorders, such as generalized anxiety disorder, separation anxiety disorder,
      social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder.
      Disorder-specific treatment methods and innovations, particularly computer
      assisted methods of delivery for cognitive behavioral therapy (CBT) will be
      reviewed. Additionally, the paper will discuss novel psychopharmacological
      compounds (e.g., D-cycloserine, riluzole, memantine, and anticonvulsant
      medications). Available evidence for the efficacy of novel medication strategies
      in adult studies and implications for their use in pediatrics will be discussed.

PMID- 24279894
TI  - New strategies and findings for behavioral interventions in autism spectrum
      disorders.
AB  - Behavioral interventions are the major source of change for children with autism
      spectrum disorders and a major cost to families and government. In the last 5
      years, a number of carefully designed intervention studies have provided new
      information about the effects of caregiver training and direct instruction on
      behavior treatments. Outcomes of these interventions are neither easily assessed
      nor simple, but are dependent on child characteristics as well as caregiver
      skills and attitudes. Some interventions aimed at specific skills have similar
      results, yet there is growing evidence that child interventions may have
      different effects than caregiver training, although both may affect outcomes in
      the long term. New research strategies and findings are discussed, with a focus
      on how underlying behaviors and specific components may contribute to
      intervention outcomes. 

PMID- 24279896
TI  - Gibberellin is not a regulator of miR156 in rice juvenile-adult phase change.
AB  - Plant hormone gibberellin (GA) promotes juvenile-adult phase change in higher
      plants. To confirm the functions of GA in rice, I used dwarf mutant d18-dy. d18
      dy is a loss-of-function allele of D18, which encodes GA3ox2. d18-dy mutant
      exhibited long juvenile phase in morphological traits such as the size of the
      shoot apical meristem (SAM), shape of leaf blades, presence or absence of midribs
      and node-internode differentiation in stem. In contrast, expression patterns of
      juvenile-adult phase change markers miR156 and miR172 were similar between wild
      type and d18-dy. In addition, d18-dy mutation and GA did not affect expression
      levels of downstream genes of miR156. GA does not function upstream of miR156 in
      juvenile-adult phase change. 

PMID- 24279898
TI  - Child restraint use in Canadian provinces with and without legislation in 2010.
AB  - OBJECTIVES: When used correctly, child safety seats reduce the risk of injury to
      a child passenger compared to seat belts. The objectives of this study are to (1)
      describe restraint use among Canadian children ages 4-8 years in 2010; (2)
      compare child safety seat use between provinces with new legislation (post-2006),
      old legislation (pre-2006), and without legislation; and (3) compare child safety
      seat use rates from 2006 to 2010. METHODS: Roadside observational surveys of
      child restraint use were performed in 2006 and 2010 using a nationally
      representative stratified sample. Proportions of restraint use, correct use
      (i.e., child safety seats and booster seats) in 4- to 8-year-old children was
      examined between 3 groups: provinces with new legislation (i.e., child safety
      seat legislation that included implementation of specific legislation for booster
      seat use for child passengers ages 4-8 years), old legislation, and no
      legislation. RESULTS: There were 4048 children observed as passengers in motor
      vehicles. In provinces with new legislation, 84 percent (95% confidence interval
      [CI], 72.2-90.8) of children were restrained compared to 94.9 percent (95% CI,
      93.0-96.7) in provinces with old legislation, and 81.8 percent (95% CI, 77.3
      86.3) in provinces without legislation. Correct use of child restraint was 54.1
      percent (95% CI, 48.0-60.3) in provinces with new legislation, 29.5 percent (95%
      CI, 25.9-33.2) in provinces with old legislation, and 52.0 percent (43.0-61.0) in
      provinces without legislation in 2010. CONCLUSION: The findings from this study
      suggest that child safety seat legislation has an impact on restraint use in
      Canada. Despite the increase in rates of child safety seat use in provinces with
      new legislation and stable rates in provinces with old legislation, use rates
      remain low. Injury prevention strategies including further surveillance,
      interventions, and enforcement of restraint use in children are important to
      decrease motor vehicle related injury and death.

PMID- 24279897
TI  - BORIS/CTCFL is an RNA-binding protein that associates with polysomes.
AB  - BACKGROUND: BORIS (CTCFL), a paralogue of the multifunctional and ubiquitously
      expressed transcription factor CTCF, is best known for its role in
      transcriptional regulation. In the nucleus, BORIS is particularly enriched in the
      nucleolus, a crucial compartment for ribosomal RNA and RNA metabolism. However,
      little is known about cytoplasmic BORIS, which represents the major pool of BORIS
      protein. RESULTS: We show, firstly, that BORIS has a putative nuclear export
      signal in the C-terminal domain. Furthermore, BORIS associates with mRNA in both
      neural stem cells and young neurons. The majority of the BORIS-associated
      transcripts are different in the two cell types. Finally, by using polysome
      profiling we show that BORIS is associated with actively translating ribosomes.
      CONCLUSION: We have demonstrated the RNA binding properties of cellular BORIS and
      its association with actively translating ribosomes. We suggest that BORIS is
      involved in gene expression at both the transcriptional and post-transcriptional
      levels.

PMID- 24279899
TI  - Degradation of dibenzofuran via multiple dioxygenation by a newly isolated
      Agrobacterium sp. PH-08.
AB  - AIMS: To demonstrate the biodegradation of dibenzofuran (DF) and its structural
      analogs by a newly isolated Agrobacterium sp. PH-08. METHODS AND RESULTS: To
      assess the biodegradation potential of newly isolated Agrobacterium sp. PH-08,
      various substrates were evaluated as sole carbon sources in growth and
      biotransformation experiments. ESI LC-MS/MS analysis revealed the presence of
      angular degrading by-products as well as lateral dioxygenation metabolites in the
      upper pathway. The metabolites in the lower pathway also were detected. In
      addition, the cometabolically degraded daughter compounds of DF-related compounds
      such as BP and dibenzothiophene (DBT) in dual substrate degradation were
      observed. Strain PH-08 exhibited the evidence of meta-cleavage pathway as
      confirmed by the activity and gene expression of catechol-2,3-dioxygenase.
      CONCLUSIONS: Newly isolated bacterial strain, Agrobacterium sp. PH-08, grew well
      with and degraded DF via both angular and lateral dioxygenation as demonstrated
      by metabolites identified through ESI LC-MS/MS and GC-MS analyses. The other
      heterocyclic pollutants were also cometabolically degraded. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Few reports have described the complete degradation of DF by
      a cometabolic lateral pathway. Our study demonstrates the novel results that the
      newly isolated strain utilized the DF as a sole carbon source and mineralized it
      via multiple dioxygenation.

PMID- 24279901
TI  - Propeller-shaped fused oligothiophenes: a remarkable effect of the topology of
      sulfur atoms on columnar stacking.
AB  - Propeller-shaped regioisomers of fused oligothiophenes F9T(endo), F9T(anti), and
      F9T(exo) were successfully synthesized. DFT calculations indicated that their
      core parts are distorted from planarity due to intramolecular steric repulsions
      involving large sulfur atoms. In contrast with soft crystalline F9T(anti) and
      F9T(exo), F9T(endo) self-assembles into a hexagonal columnar liquid crystal
      (Col(h) LC), displaying a clear X-ray diffraction (XRD) due to its stacked pi
      conjugated core. In each LC column, well-organized intermolecular S-S contacts
      are developed triple-helically along the columnar axis with a helical pitch of
      4.04 nm. Among LC semiconductors reported to date, Col(h) LC F9T(endo) displays a
      top-class charge-carrier mobility (0.18 cm(2) V(-1) s(-1)) with a distinct
      ambipolar character featuring well-balanced hole and electron mobilities. A thin
      film, prepared by mixing F9T(endo) with soluble fullerene PCBM, shows a
      photovoltaic response, when the fullerene content is large enough to compensate a
      small absorptivity of F9T(endo) for visible light.

PMID- 24279902
TI  - Effects of water, sodium hypochlorite, peroxyacetic acid, and acidified sodium
      chlorite on in-shell hazelnuts inoculated with Salmonella enterica serovar
      Panama.
AB  - Recent foodborne disease outbreaks involving minimally processed tree nuts have
      generated a need for improved sanitation procedures. Chemical sprays and dips
      have shown promise for reducing pathogens on fresh produce, but little research
      has been conducted for in-shell hazelnuts. This study analyzed the effectiveness
      of 3 chemical sanitizers for reducing Salmonella on in-shell hazelnuts.
      Treatments of water, sodium hypochlorite (NaOCl; 25 and 50 ppm), peroxyacetic
      acid (PAA; 80 and 120 ppm), and acidified sodium chlorite (ASC; 450, 830, and
      1013 ppm) were sprayed onto hazelnut samples inoculated with Salmonella enterica
      serovar Panama. Hazelnut samples were immersed in liquid cultures of S. Panama
      for 24 h, air-dried, and then sprayed with water and chemical treatments.
      Inoculation achieved S. Panama populations of approximately 8.04 log
      CFU/hazelnut. Surviving S. panama populations were evaluated using a nonselective
      medium (tryptic soy agar), incubated 3 h, and then overlaid with selective media
      (xylose lysine deoxycholate agar). All of the chemical treatments significantly
      reduced S. Panama populations (P <= 0.0001). The most effective concentrations of
      ASC, PAA, and NaOCl treatments reduced populations by 2.65, 1.46, and 0.66 log
      units, respectively. ASC showed the greatest potential for use as a postharvest
      sanitation treatment. 

PMID- 24279903
TI  - Extracellular ligninolytic enzymes production by Pleurotus eryngii on
      agroindustrial wastes.
AB  - Pleurotus eryngii (DC.) Gillet (MCC58) was investigated for its ligninolytic
      ability to produce laccase (Lac), manganese peroxidase (MnP), aryl alcohol
      oxidase (AAO), and lignin peroxidase (LiP) enzymes through solid-state
      fermentation using apricot and pomegranate agroindustrial wastes. The reducing
      sugar, protein, lignin, and cellulose levels in these were studied. Also, the
      production of these ligninolytic enzymes was researched over the growth of the
      microorganism throughout 20 days, and the reducing sugar, protein, and nitrogen
      levels were recorded during the stationary cultivation at 28 +/- 0.5 degrees C.
      The highest Lac activity was obtained as 1618.5 +/- 25 U/L on day 12 of
      cultivation using apricot. The highest MnP activity was attained as 570.82 +/- 15
      U/L on day 17 in pomegranate culture and about the same as apricot culture. There
      were low LiP activities in both cultures. The maximum LiP value detected was
      16.13 +/- 0.8 U/L in apricot cultures. In addition, AAO activities in both
      cultures showed similar trends up to day 17 of cultivation, with the highest AAO
      activity determined as 105.99 +/- 6.3 U/L on day 10 in apricot cultures.
      Decolorization of the azo dye methyl orange was also achieved with produced
      ligninolytic enzymes by P. eryngii using apricot and pomegranate wastes.

PMID- 24279905
TI  - Mapping genome-wide transcription factor binding sites in frozen tissues.
AB  - BACKGROUND: Genome-wide maps of transcription factor binding sites in primary
      tissues can expand our understanding of genome function, transcriptional
      regulation, and genetic alterations that contribute to disease risk. However,
      almost all genome-wide studies of transcription factors have been in cell lines,
      and performing these experiments in tissues has been technically challenging and
      limited in throughput. RESULTS: Here we outline a simple strategy for mapping
      transcription factor binding sites in frozen tissues that utilizes dry
      pulverization of samples and is scalable for high-throughput analyses. We show
      that the method leads to accurate and reproducible chromatin immunoprecipitation
      next-generation sequencing (ChIP-seq) data, and is highly sensitive, identifying
      high-quality transcription factor binding sites from chromatin corresponding to
      only 5 mg of liver tissue. CONCLUSIONS: The enhanced reproducibility, robustness,
      and sensitivity of the dry pulverization method, in addition to the ease of
      implementation and scalability, makes ChIP-seq in primary tissues a widely
      accessible assay.

PMID- 24279906
TI  - Physicochemical stability of captopril and enalapril extemporaneous formulations
      for pediatric patients.
AB  - The prevalence of hypertension among children has been increasing. Community and
      Hospital Pharmacists are often challenged to provide an oral liquid
      extemporaneous formulation for pediatric patients, because there are no
      appropriate dosage drugs to the specific needs of the child. The objective of
      this study is to choose and develop suitable pediatric extemporaneous
      formulations for captopril and enalapril maleate and to determine their
      physicochemical stability. A survey was carried out to evaluate the extent of
      dispensation of these drugs in Hospitals in Spain. Stability studies of
      formulations have been studied according to ICH normative at 5, 25 and 40 
      degrees C. Three samples from each temperature were withdrawn and assessed for
      stability on days 0, 15, 30, 50 and 90 using a high-performance liquid
      chromatography (HPLC) mass spectrometer assay. Rheological studies were carried
      out to ensure the maintenance of the physical characteristics of these non
      Newtonian fluids. Captopril and enalapril maleate formulations used the pure drug
      and were stable during 50 days at 5  degrees C. We have developed easy
      antihypertensive oral liquid extemporaneous formulations for pediatric patients
      with physical and chemical stability higher than those provided by the majority
      of Hospitals. 

PMID- 24279904
TI  - A randomized controlled trial investigating the neurocognitive effects of
      Lacprodan(r) PL-20, a phospholipid-rich milk protein concentrate, in elderly
      participants with age-associated memory impairment: the Phospholipid Intervention
      for Cognitive Ageing Reversal (PLICAR): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Age-related cognitive decline (ARCD) is of major societal concern in
      an ageing population, with the development of dietary supplements providing a
      promising avenue for amelioration of associated deficits. Despite initial
      interest in the use of phospholipids (PLs) for ARCD, in recent years there has
      been a hiatus in such research. Because of safety concerns regarding PLs derived
      from bovine cortex, and the equivocal efficacy of soybean-derived PLs, there is
      an important need for the development of new PL alternatives. Phospholipids
      derived from milk proteins represent one potential candidate treatment. METHODS:
      In order to reduce the effects of age-associated memory impairment (AAMI) the
      Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR) was developed to
      test the efficacy of a milk protein concentrate rich in natural, non-synthetic
      milk phospholipids (Lacprodan(r) PL-20). PLICAR is a randomized, double-blind,
      placebo-controlled parallel-groups study where 150 (N = 50/group) AAMI
      participants aged > 55 years will be randomized to receive a daily supplement of
      Lacprodan(r) PL-20 or one of two placebos (phospholipid-free milk protein
      concentrate or inert rice starch) over a 6-month (180-day) period. Participants
      will undergo testing at baseline, 90 days and 180 days. The primary outcome is a
      composite memory score from the Rey Auditory Verbal Learning Test. Secondary
      outcomes include cognitive (verbal learning, working memory, prospective and
      retrospective memory, processing speed and attention), mood (depression, anxiety,
      stress and visual analogue scales), cardiovascular (blood pressure, blood
      velocity and pulse wave pressure), gastrointestinal microbiota and biochemical
      measures (oxidative stress, inflammation, B vitamins and Homocysteine,
      glucoregulation and serum choline). Allelic differences in the Apolipoprotein E
      and (APOE) and Methylenetetrahydrofolate reductase (MTHFR) gene will be included
      for subgroup analysis. A subset (N = 60; 20/group)) will undergo neuroimaging
      using functional magnetic resonance imaging (fMRI) and magnetoencephalography
      (MEG) in order to further explore in vivo central mechanisms of action of
      Lacprodan(r) PL-20. This study will enable evaluation of the efficacy of milk
      derived phospholipids for AAMI, and their mechanisms of action. TRIAL
      REGISTRATION: The trial is jointly funded by Arla Foods and Swinburne University
      of Technology, currently recruiting and is registered on the Australian New
      Zealand Clinical Trials Registry as ACTRN12613000347763.

PMID- 24279907
TI  - Safety and efficacy of Nasya/Prevalin in reducing symptoms of allergic rhinitis.
AB  - BACKGROUND: Nasya/Prevalin is a natural, drug-free nasal spray for treatment and
      prevention of allergic rhinitis. Because of its thixotropic property, it forms a
      barrier on the nasal mucosa, preventing allergen contact. This study assesses the
      clinical efficacy and safety of Nasya/Prevalin in a nasal provocation test with
      house dust mite allergens. METHODOLOGY/PRINCIPAL: In this randomised, double
      blind, placebo-controlled trial, 20 subjects suffering from allergic rhinitis
      because of house dust mite allergens received a single dose of Nasya/Prevalin or
      saline spray before allergen challenge. Total nasal symptom score and total
      ocular symptom score were assessed 15, 30, 60, 75, 90, 120 and 240 min after
      challenge. Further, the appearance of the mucosa was examined by rhinoscopy.
      RESULTS: A single treatment with Nasya/Prevalin led to a significant reduction of
      TNSS at 60, 75 and 90 min after dust mite allergen challenge as compared with
      placebo (pVCAS  = 0.021, pVCAS  = 0.035, pVCAS  = 0.036, respectively). Mucosa
      changes assessed by the rhinoscopic score (on swelling, secretion and colour)
      were significantly worse in the placebo group compared with the Nasya/Prevalin
      group (P = 0.033). Nasya/Prevalin was well tolerated, and the safety was
      comparable with placebo. CONCLUSIONS: Treatment with Nasya/Prevalin was effective
      in preventing allergic reactions induced by dust mite allergen challenge.

PMID- 24279909
TI  - Balancing water sustainability and public health goals in the face of growing
      concerns about antibiotic resistance.
AB  - Global initiatives are underway to advance the sustainability of urban water
      infrastructure through measures such as water reuse. However, there are growing
      concerns that wastewater effluents are enriched in antibiotics, antibiotic
      resistant bacteria, and antibiotic resistance genes, and thus could serve as a
      contributing factor to growing rates of antibiotic resistance in human
      infections. Evidence for the role of the water environment as a source and
      pathway for the spread of antimicrobial resistance is examined and key knowledge
      gaps are identified with respect to implications for sustainable water systems.
      Efforts on the part of engineers along with investment in research in
      epidemiology, risk assessment, water treatment and water delivery could advance
      current and future sustainable water strategies and help avoid unintended
      consequences. 

PMID- 24279908
TI  - Risk for transmission of Naegleria fowleri from solid organ transplantation.
AB  - Primary amebic meningoencephalitis (PAM) caused by the free-living ameba (FLA)
      Naegleria fowleri is a rare but rapidly fatal disease of the central nervous
      system (CNS) affecting predominantly young, previously healthy persons. No
      effective chemotherapeutic prophylaxis or treatment has been identified.
      Recently, three transplant-associated clusters of encephalitis caused by another
      FLA, Balamuthia mandrillaris, have occurred, prompting questions regarding the
      suitability of extra-CNS solid organ transplantation from donors with PAM. During
      1995-2012, 21 transplant recipients of solid organs donated by five patients with
      fatal cases of PAM were reported in the United States. None of the recipients
      developed PAM, and several recipients tested negative for N. fowleri by serology.
      However, historical PAM case reports and animal experiments with N. fowleri,
      combined with new postmortem findings from four patients with PAM, suggest that
      extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease
      transmission via transplantation. The risks of transplantation with an organ
      possibly harboring N. fowleri should be carefully weighed for each individual
      recipient against the potentially greater risk of delaying transplantation while
      waiting for another suitable organ. In this article, we present a case series and
      review existing data to inform such risk assessments. 

PMID- 24279910
TI  - Glabrous Rice 1, encoding a homeodomain protein, regulates trichome development
      in rice.
AB  - BACKGROUND: Glabrous rice, which lacks trichomes on the rice epidermis, is
      regarded as an important germplasm resource in rice breeding. Trichomes are
      derived from aerial epidermal cells and used as a model to study the cell fate
      determination in plant. In Arabidopsis, the molecular mechanisms of trichome
      development have been well studied. However, little is known about the molecular
      basis of trichome development in rice. RESULTS: In this study, near isogenic
      lines harboring the glabrous rice 1 locus were developed. By a map-based
      approach, we narrowed down the locus to a 21-kb DNA region harboring two genes.
      One of the genes named Glabrous Rice 1 (GLR1), which is most likely the
      candidate, encodes a homeodomain protein containing the WOX motif. Constitutive
      Expression of GLR1 could partially complement the glabrous phenotype of NILglr1.
      The knock down of GLR1 by RNA interference led to a significant decrease in
      trichome number on the leaves and glumes of the RNAi transgenic plants.
      CONCLUSION: GLR1 plays an important role in rice trichome development and will
      contribute to breeding of glabrous elite rice varieties.

PMID- 24279912
TI  - Xanthomonas euvesicatoria type III effector XopQ interacts with tomato and pepper
      14-3-3 isoforms to suppress effector-triggered immunity.
AB  - Effector-triggered immunity (ETI) to host-adapted pathogens is associated with
      rapid cell death at the infection site. The plant-pathogenic bacterium
      Xanthomonas euvesicatoria (Xcv) interferes with plant cellular processes by
      injecting effector proteins into host cells through the type III secretion
      system. Here, we show that the Xcv effector XopQ suppresses cell death induced by
      components of the ETI-associated MAP kinase cascade MAPKKKalpha MEK2/SIPK and by
      several R/avr gene pairs. Inactivation of xopQ by insertional mutagenesis
      revealed that this effector inhibits ETI-associated cell death induced by
      avirulent Xcv in resistant pepper (Capsicum annuum), and enhances bacterial
      growth in resistant pepper and tomato (Solanum lycopersicum). Using protein
      protein interaction studies in yeast (Saccharomyces cerevisiae) and in planta, we
      identified the tomato 14-3-3 isoform SlTFT4 and homologs from other plant species
      as XopQ interactors. A mutation in the putative 14-3-3 binding site of XopQ
      impaired interaction of the effector with CaTFT4 in yeast and its virulence
      function in planta. Consistent with a role in ETI, TFT4 mRNA abundance increased
      during the incompatible interaction of tomato and pepper with Xcv. Silencing of
      NbTFT4 in Nicotiana benthamiana significantly reduced cell death induced by
      MAPKKKalpha. In addition, silencing of CaTFT4 in pepper delayed the appearance of
      ETI-associated cell death and enhanced growth of virulent and avirulent Xcv,
      demonstrating the requirement of TFT4 for plant immunity to Xcv. Our results
      suggest that the XopQ virulence function is to suppress ETI and immunity
      associated cell death by interacting with TFT4, which is an important component
      of ETI and a bona fide target of XopQ. 

PMID- 24279911
TI  - Light activation of Staphylococcus aureus toxin YoeBSa1 reveals guanosine
      specific endoribonuclease activity.
AB  - The Staphylococcus aureus chromosome harbors two homologues of the YefM-YoeB
      toxin-antitoxin (TA) system. The toxins YoeBSa1 and YoeBSa2 possess ribosome
      dependent ribonuclease (RNase) activity in Escherichia coli. This activity is
      similar to that of the E. coli toxin YoeBEc, an enzyme that, in addition to
      ribosome-dependent RNase activity, possesses ribosome-independent RNase activity
      in vitro. To investigate whether YoeBSa1 is also a ribosome-independent RNase, we
      expressed YoeBSa1 using a novel strategy and characterized its in vitro RNase
      activity, sequence specificity, and kinetics. Y88 of YoeBSa1 was critical for in
      vitro activity and cell culture toxicity. This residue was mutated to o
      nitrobenzyl tyrosine (ONBY) via unnatural amino acid mutagenesis. YoeBSa1-Y88ONBY
      could be expressed in the absence of the antitoxin YefMSa1 in E. coli. Photocaged
      YoeBSa1-Y88ONBY displayed UV light-dependent RNase activity toward free mRNA in
      vitro. The in vitro ribosome-independent RNase activity of YoeBSa1-Y88ONBY,
      YoeBSa1-Y88F, and YoeBSa1-Y88TAG was significantly reduced or abolished. In
      contrast to YoeBEc, which cleaves RNA at both adenosine and guanosine with a
      preference for adenosine, YoeBSa1 cleaved mRNA specifically at guanosine. Using
      this information, a fluorometric assay was developed and used to determine the
      kinetic parameters for ribosome-independent RNA cleavage by YoeBSa1. 

PMID- 24279913
TI  - A gendered perspective on military deployment.
AB  - Military deployment, especially in combat or dangerous areas, can have a strong
      influence on subsequent mental health. This effect may be intensified as a result
      of the potential stigma that admission of mental health problems indicates
      weakness. Additional mental health issues exist for female soldiers from the
      National Guard who are pulled from non-military environments to work under
      dangerous conditions far from home and traditional social support. Minimal
      documentation is available about the day-to-day, gendered experiences of
      deployment for this group of female soldiers. To provide background for
      appropriate training and support, the aim of this study was to understand better
      the experiences of military deployment for women in the National Guard. We used
      content analysis to analyze individual, semi-structured interviews with a sample
      of 42 women from 7 U.S. National Guard units who were deployed in combat areas.
      Four general themes emerged about deployment experience: the general environment
      of stress, heterogeneous job responsibilities, home comes with you, and gendered
      stress. Military efforts are needed to address gender-specific issues associated
      with deployment and to develop resilience training that will optimize the mental
      health of female soldiers. 

PMID- 24279915
TI  - Is Mc1r an important regulator of non-pigmentary responses to UV radiation?
AB  - MC1R is recognized for its role in the regulation of melanin pigmentation. In
      addition, many investigators believe that it also plays a crucial role in
      immunomodulation (immunosuppression) and in melanogenesis-independent protective
      responses against ultraviolet radiation (UVR). Surprisingly, Wolnicka-Glubisz et
      al. have shown that loss of function in the MC1R has no effect on inflammatory
      responses and immunosuppression induced by UVR in C57BL/6 mice as well as on the
      degree of UVA-induced DNA damage in the epidermis and dermis. These findings, by
      challenging the existing dogmas on the precise role of MC1R in non-pigmentary
      responses to the UVR, mandate further research to either validate the presented
      data or to define to which degree these phenomena are restricted to the C57BL/6
      mouse model or are applicable to other species including humans. The alternative
      target for immunomodulation is represented by MC3R. However, cutaneous expression
      of MC3R remains to be demonstrated.

PMID- 24279914
TI  - Purinergic signaling in early inflammatory events of the foreign body response:
      modulating extracellular ATP as an enabling technology for engineered implants
      and tissues.
AB  - Purinergic signaling is a ubiquitous and vital aspect of mammalian biology in
      which purines--mainly adenosine triphosphate (ATP)--are released from cells
      through loss of membrane integrity (cell death), exocytosis, or
      transport/diffusion across membrane channels, and exert paracrine or autocrine
      signaling effects through three subclasses of well-characterized receptors: the
      P1 adenosine receptors, the P2X ionotropic nucleotide receptors, and the P2Y
      metabotropic receptors. ATP and its metabolites are released by damaged and
      stressed cells in injured tissues. The early events of wound healing, hemostasis,
      and inflammation are highly regulated by these signals through activation of
      purinergic receptors on platelets and neutrophils. Recent data have demonstrated
      that ATP signaling is of particular importance to targeting leukocytes to sites
      of injury. This is particularly relevant to the subject of implanted medical
      devices, engineered tissues, and grafts as all these technologies elicit a wound
      healing response with varying degrees of encapsulation, rejection, extrusion, or
      destruction of the tissue or device. Here, we review the biology of purinergic
      signaling and focus on ATP release and response mechanisms that pertain to the
      early inflammatory phase of wound healing. Finally, therapeutic options are
      explored, including a new class of peptidomimetic drugs based on the ATP
      conductive channel connexin43.

PMID- 24279916
TI  - NKG2C, HLA-E and their association with psoriasis.
AB  - Natural killer (NK) cell activation is regulated by the integration of signals
      from inhibitory and activating cell surface receptors. Both NKG2A and NKG2C pair
      with CD94 to form inhibitory and activating receptors specific for the HLA-E
      canonical peptide complex. HLA-E is a non-classical MHC class Ib molecule with
      limited polymorphism. It preferentially binds to and presents leader sequence
      peptides derived from classical MHC class I molecules. Wilson et al. have
      identified an association between NKG2C deficiency and psoriasis. They have also
      discovered an HLA-C-dependent association between HLA-E and psoriasis. Their
      research highlights the importance of NK cells in the pathophysiology of
      psoriasis. Herein, we propose two different models to explain the association
      between NKG2C, HLA-E and psoriasis. In the first model, we hypothesize that NKG2C
      deficiency and/or HLA-E O1:01 can inhibit the ability of NK cells to regulate
      autoreactive T cells, predisposing to psoriasis. The second model proposes that
      HLA-E 01:03 can disrupt the presentation of the psoriasis-inducing self
      determinant by HLA-C, thereby protecting against psoriasis.

PMID- 24279917
TI  - Impact of next generation sequencing on diagnostics in a genetic skin disease
      clinic.
AB  - Individuals with inherited skin diseases often pose one of the most difficult
      diagnostic challenges in dermatology. The hunt for the underlying molecular
      pathology may involve candidate gene screening or linkage analysis, which is
      usually determined by the initial history, the physical findings and laboratory
      tests. Recent technical advances in DNA sequencing, however, are shifting the
      diagnostic paradigm. Notably, next-generation sequencing allows a more
      comprehensive approach to diagnosing inherited diseases, with potential savings
      of both time and money. In the setting of a paediatric dermatology genetics
      clinic in Kuwait, we therefore performed whole-exome sequencing on seven
      individuals without a priori detailed knowledge of the patients' disorders: from
      these sequencing data, we diagnosed X-linked hypohidrotic ectodermal dysplasia
      (two cases), acrodermatitis enteropathica, recessive erythropoietic
      protoporphyria (two siblings) and localized recessive dystrophic epidermolysis
      bullosa (two siblings). All these groups of disorders are clinically and
      genetically heterogeneous, but the sequencing data proved inherently useful in
      improving patient care and avoiding unnecessary investigations. Our observations
      highlight the value of whole-exome sequencing, in combination with robust
      bioinformatics analysis, in determining the precise molecular pathology and
      clinical diagnosis in patients with genetic skin disorders, notably at an early
      stage in the clinical evaluation of these often complex disorders and thereby
      support a new paradigm for future diagnostics. 

PMID- 24279918
TI  - Calmodulin-like skin protein level increases in the differentiated epidermal
      layers in atopic dermatitis.
AB  - In atopic dermatitis (AD), the skin barrier is disturbed, and the expression of
      calcium-dependent S100 proteins and the calcium gradient is also altered in the
      epidermis. The calmodulin-like skin protein (CLSP), which is expressed in the
      differentiated epidermis, is believed to modulate the function of calcium
      dependent proteins involved in barrier formation and is significantly increased
      in the epidermis of psoriatic patients. We, therefore, investigated the CLSP
      level in skin biopsies taken from patients with acute exacerbated and non
      exacerbated AD as well as from healthy control subjects. Immunohistochemical,
      Western blot and ELISA analyses showed significant increases (P < 0.03) in CLSP
      level in the epidermis from patients with acute exacerbated AD as compared to
      that from patients with non-exacerbated AD and from control subjects. Such
      increased expression of CLSP may help re-establish a functional epidermal barrier
      in acute AD.

PMID- 24279920
TI  - The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and
      analyzing adverse events associated with US-licensed human vaccines.
AB  - BACKGROUND: Licensed human vaccines can induce various adverse events (AE) in
      vaccinated patients. Due to the involvement of the whole immune system and
      complex immunological reactions after vaccination, it is difficult to identify
      the relations among vaccines, adverse events, and human populations in different
      age groups. Many known vaccine adverse events (VAEs) have been recorded in the
      package inserts of US-licensed commercial vaccine products. To better represent
      and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as
      an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology
      (VO). RESULTS: Like OAE and VO, OVAE is aligned with the Basic Formal Ontology
      (BFO). The commercial vaccines and adverse events in OVAE are imported from VO
      and OAE, respectively. A new population term 'human vaccinee population' is
      generated and used to define VAE occurrence. An OVAE design pattern is developed
      to link vaccine, adverse event, vaccinee population, age range, and VAE
      occurrence. OVAE has been used to represent and classify the adverse events
      recorded in package insert documents of commercial vaccines licensed by the USA
      Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms,
      including 87 distinct types of VAEs associated with 63 human vaccines licensed in
      the USA. For each vaccine, occurrence rates for every VAE in different age groups
      have been logically represented in OVAE. SPARQL scripts were developed to query
      and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the
      top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs
      most frequently observed among vaccines were identified and analyzed. Asserted
      and inferred ontology hierarchies classify VAEs in different levels of AE groups.
      Different VAE occurrences in different age groups were also analyzed.
      CONCLUSIONS: The ontology-based data representation and integration using the FDA
      approved information from the vaccine package insert documents enables the
      identification of adverse events from vaccination in relation to predefined parts
      of the population (age groups) and certain groups of vaccines. The resulting
      ontology-based VAE knowledge base classifies vaccine-specific VAEs and supports
      better VAE understanding and future rational AE prevention and treatment.

PMID- 24279921
TI  - Genetic analysis of an elite super-hybrid rice parent using high-density SNP
      markers.
AB  - BACKGROUND: With an increasing world population and a gradual decline in the
      amount of arable land, food security remains a global challenge. Continued
      increases in rice yield will be required to break through the barriers to grain
      output. In order to transition from hybrid rice to super-hybrid rice, breeding
      demands cannot be addressed through traditional heterosis. Therefore, it is
      necessary to incorporate high yield loci from other rice genetic groups and to
      scientifically utilize intersubspecific heterosis in breeding lines. In this
      study, 781 lines from a segregating F2 population constructed by crossing the
      indica variety, "Giant Spike Rice" R1128 as trait donor with the japonica
      cultivar 'Nipponbare', were re-sequenced using high-throughout multiplexed
      shotgun genotyping (MSG) technology. In combination with high-density single
      nucleotide polymorphisms, quantitative trait locus (QTL) mapping and genetic
      effect analysis were performed for five yield factors (spikelet number per
      panicle, primary branches per panicle, secondary branches per panicle, plant
      height, and panicle length) to explore the genetic mechanisms underlying the
      formation of the giant panicle of R1128. Also, they were preformed to locate new
      high-yielding rice genetic intervals, providing data for super-high-yielding rice
      breeding. RESULTS: QTL mapping and genetic effect analysis for five yield factors
      in the population gave the following results: 49 QTLs for the five yield factors
      were distributed on 11 of 12 chromosomes. The super-hybrid line R1128 carries
      multiple major genes for good traits, including Sd1 for plant height, Hd1 and
      Ehd1 for heading date, Gn1a for spikelet number and IPA1 for ideal plant shape.
      These genes accounted for 44.3%, 21.9%, 6.2%, 12.9% and 10.6% of the phenotypic
      variation in the individual traits. Six novel QTLs, qph1-2, qph9-1, qpl12-1, qgn3
      1, qgn11-1and qsbn11-1 are reported here for the first time. CONCLUSIONS: High
      throughout sequencing technology makes it convenient to study rice genomics and
      makes the QTL/gene mapping direct, efficient, and more reliable. The genetic
      regions discovered in this study will be valuable for breeding in rice varieties
      because of the diverse genetic backgrounds of the rice.

PMID- 24279923
TI  - Assessment of vehicle and restraint design changes for mitigating rear seat
      occupant injuries.
AB  - OBJECTIVE: Investigate the combined effects of belt geometry, seat substructure,
      and seat belt pretensioners and load limiters on rear seat occupant injury risk.
      METHODS: An instrumented Hybrid III 5th percentile adult female dummy was
      subjected to simulated frontal impacts (Deltav = 45.8 km/h, peak acceleration =
      27.1 g). Testing was conducted on a rear seat of a typical family sedan with
      modifications allowing for adjustment in upper anchorage position, mounting of an
      antisubmarining seat pan, and the use of seat belt pretensioners with load
      limiters. RESULTS: Dummy seated posture had the strongest effect on submarining.
      Seat belt pretensioners with load limiters reduced head and femur excursion and
      decreased chest injury measurements but did not prevent submarining. The
      antisubmarining seat pan, on the other hand, prevented submarining in one case
      but could not prevent submarining with the dummy in a slouched posture. Upper
      anchorage position resulting in poor belt geometry was shown to increase both
      chest injury measures and submarining. CONCLUSIONS: The results from this study
      demonstrate the importance of an upright seated posture and the potential
      benefits of including adjustable upper anchorages to allow good sash belt fit,
      antisubmarining seat pans, belt buckles positioned near the seat bight, and seat
      belts with pretensioners and load limiters for rear seat occupants. These data
      can be used to inform the design of a system of restraints to reduce injuries to
      rear seat occupants.

PMID- 24279924
TI  - Large-scale fabrication, 3D tomography, and lithium-ion battery application of
      porous silicon.
AB  - Recently, silicon-based lithium-ion battery anodes have shown encouraging
      results, as they can offer high capacities and long cyclic lifetimes. The
      applications of this technology are largely impeded by the complicated and
      expensive approaches in producing Si with desired nanostructures. We report a
      cost-efficient method to produce nanoporous Si particles from metallurgical Si
      through ball-milling and inexpensive stain-etching. The porosity of porous Si is
      derived from particle's three-dimensional reconstructions by scanning
      transmission electron microscopy (STEM) tomography, which shows the particles'
      highly porous structure when etched under proper conditions. Nanoporous Si anodes
      with a reversible capacity of 2900 mAh/g was attained at a charging rate of 400
      mA/g, and a stable capacity above 1100 mAh/g was retained for extended 600 cycles
      tested at 2000 mA/g. The synthetic route is low-cost and scalable for mass
      production, promising Si as a potential anode material for the next-generation
      lithium-ion batteries with enhanced capacity and energy density. 

PMID- 24279922
TI  - Comprehensive analysis of MHC class II genes in teleost fish genomes reveals
      dispensability of the peptide-loading DM system in a large part of vertebrates.
AB  - BACKGROUND: Classical major histocompatibility complex (MHC) class II molecules
      play an essential role in presenting peptide antigens to CD4+ T lymphocytes in
      the acquired immune system. The non-classical class II DM molecule, HLA-DM in the
      case of humans, possesses critical function in assisting the classical MHC class
      II molecules for proper peptide loading and is highly conserved in tetrapod
      species. Although the absence of DM-like genes in teleost fish has been
      speculated based on the results of homology searches, it has not been
      definitively clear whether the DM system is truly specific for tetrapods or not.
      To obtain a clear answer, we comprehensively searched class II genes in
      representative teleost fish genomes and analyzed those genes regarding the
      critical functional features required for the DM system. RESULTS: We discovered a
      novel ancient class II group (DE) in teleost fish and classified teleost fish
      class II genes into three major groups (DA, DB and DE). Based on several
      criteria, we investigated the classical/non-classical nature of various class II
      genes and showed that only one of three groups (DA) exhibits classical-type
      characteristics. Analyses of predicted class II molecules revealed that the
      critical tryptophan residue required for a classical class II molecule in the DM
      system could be found only in some non-classical but not in classical-type class
      II molecules of teleost fish. CONCLUSIONS: Teleost fish, a major group of
      vertebrates, do not possess the DM system for the classical class II peptide
      loading and this sophisticated system has specially evolved in the tetrapod
      lineage.

PMID- 24279925
TI  - Bone marrow-derived mononuclear cell therapy in sepsis-induced acute respiratory
      distress syndrome: different insults, different effects!
AB  - Acute respiratory distress syndrome (ARDS) is one of the devastating sequelae of
      sepsis, and so far no specific promising pharmacotherapies have been proven to
      decrease mortality from it. Stem cell therapy is a novel therapy that can promote
      earlier and more effective remodeling and repair of damaged lung tissue. Bone
      marrow-derived mononuclear cells are an alternative stem cell therapy that is
      safely and easily administered on the day of harvesting and yields benefits in
      acute disease processes like ARDS. In a recent issue of Stem Cell Research and
      Therapy, Maron-Gutierrez and colleagues demonstrated that the effects of
      transfused bone marrow-derived mononuclear cells on lung mechanics, inflammation
      and mortality might be different in different septic ARDS models due to different
      insults.

PMID- 24279926
TI  - Myofibroblast differentiation: main features, biomedical relevance, and the role
      of reactive oxygen species.
AB  - SIGNIFICANCE: Myofibroblasts are prototypical fibrotic cells, which are involved
      in a number of more or less pathological conditions, from foreign body reactions
      to scarring, from liver, kidney, or lung fibrosis to neoplastic phenomena. The
      differentiation of precursor cells (not only of fibroblastic nature) is
      characterized by a complex interplay between soluble factors (growth factors such
      as transforming growth factor beta1, reactive oxygen species [ROS]) and material
      properties (matrix stiffness). RECENT ADVANCES: The last 15 years have seen very
      significant advances in the identification of appropriate differentiation
      markers, in the understanding of the differentiation mechanism, and above all,
      the involvement of ROS as causative and persistence factors. CRITICAL ISSUES: The
      specific mechanisms of action of ROS remain largely unknown, although evidence
      suggests that both intracellular and extracellular phenomena play a role. FUTURE
      DIRECTIONS: Approaches based on antioxidant (ROS-scavenging) principles and on
      the potentiation of nitric oxide signaling hold much promise in view of a
      pharmacological therapy of fibrotic phenomena. However, how to make the active
      principles available at the target sites is yet a largely neglected issue.

PMID- 24279927
TI  - Glycoside hydrolase processivity is directly related to oligosaccharide binding
      free energy.
AB  - Many glycoside hydrolase (GH) enzymes act via a processive mechanism whereby an
      individual carbohydrate polymer chain is decrystallized and hydrolyzed along the
      chain without substrate dissociation. Despite considerable structural and
      biochemical studies, a molecular-level theory of processivity that relates
      directly to structural features of GH enzymes does not exist. Here, we
      hypothesize that the degree of processivity is directly linked to the ability of
      an enzyme to decrystallize a polymer chain from a crystal, quantified by the
      binding free energy of the enzyme to the cello-oligosaccharide. We develop a
      simple mathematical relationship formalizing this hypothesis to quantitatively
      relate the binding free energy to experimentally measurable kinetic parameters.
      We then calculate the absolute ligand binding free energy of cellulose chains to
      the biologically and industrially important GH Family 7 processive cellulases
      with free energy perturbation/replica-exchange molecular dynamics. Taken with
      previous observations, our results suggest that degree of processivity is
      directly correlated to the binding free energy of cello-oligosaccharide ligands
      to GH7s. The observed binding free energies also suggest candidate polymer
      morphologies susceptible to enzyme action when compared to the work required to
      decrystallize cellulose chains. We posit that the ligand binding free energy is a
      key parameter in comparing the activity and function of GHs and may offer a
      molecular-level basis toward a general theory of carbohydrate processivity in GHs
      and other enzymes able to process linear carbohydrate polymers, such as cellulose
      and chitin synthases. 

PMID- 24279928
TI  - Texture analyses show synergetic effects of biomechanical and biochemical
      stimulation on mesenchymal stem cell differentiation into early phase
      osteoblasts.
AB  - We investigated the structural complexity and texture of the cytoskeleton and
      nucleus in human mesenchymal stem cells during early phase differentiation into
      osteoblasts according to the differentiation-induction method: mechanical and/or
      chemical stimuli. For this, fractal dimension and a number of parameters
      utilizing the gray-level co-occurrence matrix (GLCM) were calculated based on
      single-cell images after confirmation of differentiation by immunofluorescence
      staining. The F-actin and nuclear fractal dimensions were greater in both
      stimulus groups compared with the control group. The GLCM values for energy and
      homogeneity were lower in fibers of the F-actin cytoskeleton, indicating a
      dispersed F-actin arrangement during differentiation. In the nuclei of both
      stimulus groups, higher values for energy and homogeneity were calculated,
      indicating that the chromatin arrangement was chaotic during the early phase of
      differentiation. It was shown and confirmed that combined stimulation with
      mechanical and chemical factors accelerated differentiation, even in the early
      phase. Fractal dimension analysis and GLCM methods have the potential to provide
      a framework for further investigation of stem cell differentiation.

PMID- 24279930
TI  - Optimization of solid-state fermentation for phytase production by Thermomyces
      lanuginosus using response surface methodology.
AB  - A strain of Thermomyces lanuginosus, isolated from hot spring water in Turkey,
      was studied for optimization of phytase production using solid-state
      fermentation. Effects on fermentation of different production parameters such as
      substrate type, moisture, culture time, and inoculum size were investigated using
      a one-factor-at-a-time approach. Central composite design (CCD) of response
      surface methodology was applied for the optimization of four factors (culture
      temperature, initial pH, aeration area, age of seeding culture) that were
      affecting phytase production by Thermomyces lanuginosus in rice bran. Maximum
      phytase activity was achieved by using rice bran. The optimum levels of variables
      that supported maximum enzyme activity were moisture 70%, culture time 7 days,
      inoculum size 40%, culture temperature 55 degrees C, initial pH 7.5, aeration
      area 30%, age of seeding culture 5 days, sucrose 1%, and ZnSO4 2.5 mM. An overall
      10.83-fold enhancement in phytase activity (0.30 to 3.248 U) was attained due to
      the optimization.

PMID- 24279929
TI  - The metabolic demands of cancer cells are coupled to their size and protein
      synthesis rates.
AB  - BACKGROUND: Although cells require nutrients to proliferate, most nutrient
      exchange rates of the NCI60 panel of cancer cell lines correlate poorly with
      their proliferation rate. Here, we provide evidence indicating that this
      inconsistency is rooted in the variability of cell size. RESULTS: We integrate
      previously reported data characterizing genome copy number variations, gene
      expression, protein expression and exchange fluxes with our own measurements of
      cell size and protein content in the NCI60 panel of cell lines. We show that
      protein content, DNA content, and protein synthesis per cell are proportional to
      the cell volume, and that larger cells proliferate slower than smaller cells. We
      estimate the metabolic fluxes of these cell lines and show that their magnitudes
      are proportional to their protein synthesis rate and, after correcting for cell
      volume, to their proliferation rate. At the level of gene expression, we observe
      that genes expressed at higher levels in smaller cells are enriched for genes
      involved in cell cycle, while genes expressed at higher levels in large cells are
      enriched for genes expressed in mesenchymal cells. The latter finding is further
      corroborated by the induction of those same genes following treatment with
      TGFbeta, and the high vimentin but low E-cadherin protein levels in the larger
      cells. We also find that aromatase inhibitors, statins and mTOR inhibitors
      preferentially inhibit the in vitro growth of cancer cells with high protein
      synthesis rates per cell. CONCLUSIONS: The NCI60 cell lines display various
      metabolic activities, and the type of metabolic activity that they possess
      correlates with their cell volume and protein content. In addition to cell
      proliferation, cell volume and/or biomarkers of protein synthesis may predict
      response to drugs targeting cancer metabolism.

PMID- 24279932
TI  - Editorial comment.

PMID- 24279931
TI  - Effect of pH and pepsin limited hydrolysis on the structure and functional
      properties of soybean protein hydrolysates.
AB  - Effects of limited enzymatic hydrolysis with pepsin on the functional properties
      and structure characteristics of soybean proteins were investigated. Hydrolysates
      with different incubation time (10 to 900 min) were prepared. Results showed that
      SPI hydrolyzed for 60 min exhibited the best emulsibility and the ability of
      resisting freezing/thawing. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis proved that pepsin can degrade glycinin but had little effect on
      the alpha' subunit of beta-conglycinin. The structure unfolding reached the
      largest extent after incubation for 60 min and the soluble and flexible
      aggregates were formed. After 120 min, glycinin was degraded totally and beta
      conglycinin formed insoluble aggregates. Moreover, 2 methods were applied for the
      deactivation of pepsin to obtain final hydrolysates at pH 2.0 and 7.0,
      respectively. The structure analysis revealed that the unfolding extent and
      structure characteristic were different in these 2 conditions. When adjusting the
      pH value from 2.0 to 7.0, the unfolding protein molecular would reaggregate again
      at pH 7.0 due to the charge neutralization, and the hydrodynamic diameter and
      lambdamax absorbance decreased compared to pH 2.0. Moreover, some of the
      insoluble aggregates formed at pH 2.0 became soluble at pH 7.0, because of the
      salt-in phenomenon. 

PMID- 24279933
TI  - Visual event-related potentials and depression in the elderly.
AB  - Event-related potentials (ERPs) were recorded during a visual discrimination task
      from nine elderly individuals (mean=68.1 years), diagnosed as having major
      depressive disorder, and nine age-matched controls (mean=68.0 years). During the
      task, subjects pressed a switch to targets (the number 9) and ignored background
      (the number 6) and novel stimuli (random designs). Novel and target stimuli were
      both interspersed infrequently in the sequence of background stimuli. Scalp
      electrical activity was recorded from midline frontal (Fz), central (Cz), and
      parietal (Pz) sites. Depressives were characterized by lengthened response times
      and increased number of errors across the session. Speed of response was also
      found to vary directly with clinical status. Additionally, ERP correlates of
      depression in the elderly were found: N1 was more prolonged for target than non
      target stimuli in the depressed group; P2 was larger for all conditions; N2 was
      uniformly small across the scalp, whereas the controls showed small N2 amplitudes
      only at Fz; large P3s appeared in trials following the novel stimuli in the
      depressed but not in the control group. These results are interpreted in terms of
      the symptomatology associated with depression (i.e., distractability, impaired
      short-term memory or concentration, indecisiveness) and possible age-related
      changes in the ERP scalp distribution. 

PMID- 24279934
TI  - Age-Related Neostriatal Alterations in the Rat: Failure of L-DOPA to Alter
      Behavior.
AB  - Age differences in rotational behavior were examined in young (6 mo) and old (24
      mo) Wistar rats lesioned in the left substantia nigra with 6-OHDA. Young animals
      showed a 50% increase in rotational behavior with L-DOPA pretreatment and a 15
      20% increase following L-tyrosine pretreatment. However, neither L-DOPA nor L
      tyrosine pretreatment potentiated amphetamine-induced rotational behavior of
      senescent animals. Pretreatment with tranylcypromine, an MAO inhibitor, did not
      enhance rotational behavior in either group. After assessing rotational responses
      to amphetamine, half of each age group was given L-DOPA 1 hr prior to sacrifice,
      and right (RS) and left striatal (LS) levels of dopamine (DA) were examined in
      all groups. Comparable LS depletion was found in both age groups. L-DOPA
      significantly raised DA levels in the RS of the young animals while causing no
      change effect in old animals although the amount of L-DOPA entering the striatum
      was even higher in the senescent animals. Striatal tyrosine hydroxylase showed
      only a small decrease (15%) in activity, while DOPA decarboxylase activity showed
      no significant age-related decline. Despite the lack of substantial decrease in
      enzyme activity, the results indicate an age-dependent decrease in the capacity
      for L-DOPA potentiation of rotational behavior. Defects may exist at the level of
      elevation of the functional pool of DA, the release of DA, or the interaction of
      DA with a decreasing number of a class of DA receptors involved in motor control.

PMID- 24279935
TI  - Positron emission tomography in the study of aging and senile dementia.
AB  - (18)F-2-deoxy-2-fluoro-D-glucose ((18)FDG) is a positron emitting tracer for rate
      of glucose utilization in brain. When used in conjunction with positron emission
      tomography (PET), the PET-FDG technique permits in vivo quantitation of regional
      brain metabolism in man. We have applied this technique to the study of regional
      brain function in normal aging and senile dementia. Preliminary results for 7
      patients with senile dementia of the Alzheimer's type (SDAT) and 3 elderly normal
      subjects indicated a large, statistically significant (p < 0.01) diminution in
      rate of glucose utilization in SDAT. Furthermore, the degree of diminution in
      metabolic activity in SDAT was highly correlated with objective measures of
      degree of cognitive impairment. These results demonstrate the feasibility and
      potential utility of the PET-FDG technique for studying regional brain function
      in normal aging and dementia. 

PMID- 24279936
TI  - Visual acuity and foveal cone density in the retina of the aged rhesus monkey.
AB  - The specific aims of this study were to examine age differences in visual acuity
      among young adult (5 years), middle aged (12 years) and aged (22 years) rhesus
      monkeys in relation to foveal cone density in the diurnal duplex retina.
      Classically, acuity has been defined as the reciprocal of the least resolvable
      detail measured in minutes of visual angle. The minimum separable binocular
      acuity mean of the young adult group was 0.83 +/- 0.11, middle age acuity mean
      was 0.86 +/- 0.12, and the acuity mean of the aged monkeys was 2.0 - 0.70 minutes
      of visual angle. According to analysis of variance and multiple range tests for
      specific group means, the 0.83' acuity m mean of the young, and the 0.86' acuity
      mean of the middle age group did not differ significantly, whereas the 2.0'
      acuity mean of the old group differed significantly from the 2 younger age
      groups. Foveal cone density was determined morphometrically by assesmeent of cone
      inner segment width, and absolute cone inner segment number per 100 Am along the
      horizontal meridian of the pure cone, rod free 1 degrees  * 1 degrees  foveola.
      Foveal cone density decreased significantly from 44.16 per 100 Am in the middle
      age group to 39.00 per 100 Am in the old macaque group. Since the diurnal macaque
      is of the same taxonomic order as man, and the visual systems of the two species
      are directly comparable in terms of ac acuity and the central receptive field
      organization of the retino-geniculo-striate system, it may be concluded that the
      macaque may represent an attractive and valid model for studies of aging in
      photopic and scotopic vision of diurnal primates, including man. 

PMID- 24279937
TI  - Positive Feedback by Ovarian Hormones on Prolactin and LH in Old Versus Young
      Female Rats.
AB  - The purpose of this investigation was to determine whether any differences could
      be demonstrated in the ability of old versus young ovariectomized rats to release
      prolactin and LH in response to ovarian steroid administration. Female Long Evans
      rats 20-24 months of age and 4 months of age were ovariectomized. Fourteen days
      later, each rat was injected with estradiol benzoate, followed three days later
      by an injection of progesterone. Blood was collected from an intra-atrial cannula
      for eight hrs after progesterone treatment for radioimmunoassay of prolactin and
      LH. Basal plasma levels of prolactin were higher in the old than in the young
      rats. The young rats showed a marked rise in plasma prolactin and LH in response
      to progesterone, whereas the old rats exhibited no elevation in prolactin and a
      smaller increase in LH than in young rats. Changes in hypothalamic function in
      the old female rats are believed to account for the differences observed. 

PMID- 24279938
TI  - Memory deficits in aged cebus monkeys and facilitation with central
      cholinomimetics.
AB  - Cebus monkeys of 3 different age groups were trained to perform an automated
      behavioral task (delayed response), intended to measure recent memory ability. In
      in initial study, the aged monkeys (18 years and older) exhibit prprogressively
      greater performance impairments (relative to young monkeys) as they were required
      to remember the location of a visual stimulus for increasingly longer durations
      (0 to 20 sec). This deficits replicated previously published results from aged
      Rhesus monkeys and appeared similar to the primary memory deficits reported in
      elderly humans and demented patients. In subsequent studies, the effects of three
      different cholinomimetics were evaluated for their ability to improve the aged
      monkey's performance on this task. Each monkey was tested under several acute
      doses of the cholinergic precursor, choline, the anticholinesterase,
      physostigmine, and the cholinergic muscarinic receptor agonist, arecoline. The
      results revealed clear differences in the ability of these drugs to improve
      performance on this task. Choline exerted no apparent effects in the aged monkeys
      at any dose tested. Physostigmine clearly enhanced performance in certain aged
      monkeys, but the optimal dose varied dramatically between subjects, replicating
      previously published results with aged Rhesus monkeys and humans. Arecoline
      produced clear improvement within a restricted dose range, with little variation
      in optimal dose between subjects. In addition to demonstrating differences in the
      effects of different cholinomimetics on memory performance in aged primates,
      these data also suggest a possible rationale for future investigations. Assuming
      that each of these drugs primarily affected cholinergic function in the manner
      conventionally attributed, these data suggest that, within the cholinergic
      system, the more directly one stimulates the receptor, the more one might expect
      robust and consistent effects on memory performance in aged subjects. 

PMID- 24279939
TI  - Pituitary and hypothalamic concentration of met-enkephalin in young and old rats.
AB  - Anterior pituitary and hypothalamic concentration of met-enkephalin was measured
      by a specific radioimmunoassay in old (22-24 months) and young (4-6 months) rats.
      The old rats were reproductively abnormal and based on their vaginal cytology,
      they were further classified under pseudopregnant, irregular cycle and constant
      estrus groups. All old rats had significantly higher concentration of met
      enkephalin in the anterior pituitary gland when compared with young rats in
      estrus. Pseudopregnant rats had the highest concentration of met-enkephalin (7.38
      +/- 1.72 ng met-enkephalin/mg protein, mean +/- SEM) followed by rats with
      irregular cycles (3.07 +/- 1.54) and old rats exhibiting constant estrus (2.22 +/
      0.47). Young rats in estrus had a mean concentration of 0.13 +/- 0.08 ng met
      enkephalin/mg protein in the anterior pituitary gland. However, there was no
      significant difference in the hypothalamic concentration of met-enkephalin of old
      animals when compared with young animals. 

PMID- 24279940
TI  - Cardiovascular, sympathetic and adrenal cortical responsiveness of aged fischer
      344 rats to stress.
AB  - While resting, Fischer-344 rats underwent a decrease in heart rate and an
      increase in diastolic blood pressure and plasma norepinephrine with increasing
      age. The blood pressure of adult rats increased significantly during a 3 minute
      immobilization. The blood pressure of old rats failed to increase during stress,
      decreased to below control level immediately following the termination of stress
      and they died within 24 hours. Three minutes of stress failed to increase the
      heart rate of old rats while 30 min of stress produced a small increase in the
      heart rate, approximately sol1 3 to sol1 2 of the increase seen in younger rats.
      The old rats showed no decrease in the maximal adrenergic medullary or cortical
      responses to stress, but they had a prominent 3 min delay in the maximal peak of
      norepinephrine release. The 30 minute stress caused a greater increase in plasma
      epinephrine in old rats than in adult rats while it initiated a decrease in beta
      adrenergic responses such as heart rate and plasma glucose. The present results
      indicate that old rats lose their ability to cope with acute stress due to
      decreased adrenergic responsiveness and increased "shock" reaction. 

PMID- 24279941
TI  - Immunoglobulins, cognitive status and duration of illness in alzheimer's disease.
AB  - Immunologic changes have been reported in the dementing illnesses of mid and late
      life. The results of two studies of drug-free males meeting research diagnostic
      criteria for primary neuronal degeneration of the Alzheimer's type suggest that
      serum IgG levels decrease with the progression of dementia. Serum IgG levels were
      inversely correlated with duration of illness and the levels of psychiatric
      symptomatology. Performance on the mini-mental status examination was positively
      associated with serum IgG concentrations. 

PMID- 24279942
TI  - Aging in rodent brain: alteration in astrocyte population.
AB  - A method for the preparation of bulk isolated glial cells was modified to provide
      astrocytes suitable for biochemical analysis. Using this method, the astrocyte
      enriched fraction from senescent mouse or rat brain stem could not be recovered
      from the sucrose interface at which 6 month brain stem astroglia accumulated. An
      alteration in the buoyant density of the senescent glial cells was demonstrated
      by using continuous diatrizoate gradients. The involvement of the astrocyte cell
      population in this age-related shift in buoyant density was confirmed using
      antiserum specific for glial fibrillary acidic protein. 

PMID- 24279943
TI  - Reduced febrile responses to peripheral and central administration of pyrogen in
      aged squirrel monkeys.
AB  - There is long-standing controversy as to whether fever capacity is reduced in
      aged man. Although loss of this cardinal sign of disease would be an impediment
      to diagnosis and treatment, there has been no previous research on altered
      febrile responses using aged primate models. In the present experiments the
      febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over
      14 years old and in one-third of those 10-14 years of age compared with that of
      younger animals. In response to injections of endotoxin into the lateral cerebral
      ventricle (ICV), animals over 10 years old showed small or no fevers. Injections
      of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen
      and prostaglandin, augmented fever caused by IV and ICV endotoxin and
      hyperthermia caused by ICV PGE2 in animals under 10 years of age. However, in
      older animals probenecid increased fever caused by ICV endotoxin only, although
      the increased response was still less than one quarter that of younger animals.
      The results indicate that old squirrel monkeys have decreased febrile responses
      that may be traced to alterations in central sensitivity to pyrogens. 

PMID- 24279944
TI  - Diagnostic utility of flexible bronchoscopy in elderly patients.
AB  - BACKGROUND: In the elderly population, diagnosis and initial treatment should be
      considered as soon as possible because of high disease incidence and
      complications. We aimed to evaluate the findings of flexible bronchoscopy (FB)
      and determine the diagnostic utility of FB in patients 65 years old and older.
      METHOD: We retrospectively evaluated FB results. Demographic data, clinical and
      bronchoscopic findings, diagnostic procedures during FB and incidence of accurate
      diagnosis with FB both in patients 65 years old and older and in younger patients
      were determined. RESULTS: A total of 745 patients [younger patients (<65 years, n
      = 378, F/M: 120/258) and older patients (>=65 years, n = 367, F/M: 88/279)] who
      underwent FB at our clinic between 2009 and 2012 were included. The mean age of
      older patients was 72.6 +/- 5.8 years, while the mean age of younger patients was
      50.9 +/- 11.7 years. Overall, 188 older patients (51.2%) had an accurate
      diagnosis with the procedures used during bronchoscopy, and 179 younger patients
      (47.3%) had a final diagnosis with these procedures. The diagnostic utility of FB
      did not differ significantly between study groups (P = 0.291). During FB, 326
      older patients (88.8%) had no complication, and 343 younger patients (90.7%) had
      no complications. No statistically significant difference was found between older
      and younger patients in terms of complications during FB (P = 0.389). CONCLUSION:
      The results of this study indicate the high diagnostic value of FB together with
      low complication rates in patients aged 65 years and older.

PMID- 24279945
TI  - Extreme elemental processing in a high schizotypy population: relation to
      cognitive deficits.
AB  - The cognitive deficits observed in schizophrenia have been characterized as a
      failure to utilize task-setting information to guide behaviour, especially in
      situations in which there is response conflict. Recently, we have provided
      support for this account; high schizotypy individuals demonstrated inferior
      biconditional discrimination performance compared to low scorers, but were not
      impaired on a simple discrimination that did not require the use of task-setting
      cues. These results may, however, also be explained by the way in which
      individuals with high schizotypy process stimulus compounds. Here, we examine the
      initial approaches to solving biconditional and control discrimination tasks of
      participants with high and low schizotypy scores. In particular, we focus on
      performance during the first block of training trials to capture processing style
      before the acquisition of the discrimination tasks. Participants scoring highly
      on the introvertive anhedonia subscale (which has been allied to the negative and
      cognitive symptoms of schizophrenia) demonstrated better biconditional
      performance during the first block of training trials than did low-schizotypy
      individuals, consistent with a highly elemental approach to stimulus processing.
      Subsequent recognition tests confirmed this analysis demonstrating that the
      pattern of performance observed in participants with high schizotypy was
      associated with a failure to discriminate conjunctions of items that had been
      seen before from those that had not. These results suggest that the
      negative/cognitive symptoms of schizophrenia may reflect an extreme bias towards
      elemental, as opposed to configural, processing of stimulus conjunctions. 

PMID- 24279946
TI  - Defining HLA-specific antibodies.

PMID- 24279947
TI  - Integrating pharmacists into primary care teams: barriers and facilitators.
AB  - OBJECTIVES: This study evaluated the barriers and facilitators that were
      experienced as pharmacists were integrated into 23 existing primary care teams
      located in urban and rural communities in Saskatchewan, Canada. METHODS:
      Qualitative design using data from one-on-one telephone interviews with
      pharmacists, physicians and nurse practitioners from the 23 teams that integrated
      a new pharmacist role. Four researchers from varied backgrounds used thematic
      analysis of the interview transcripts to determine key themes. The research team
      met on multiple occasions to agree on the key themes and received written
      feedback from an external auditor and two of the original interviewees. KEY
      FINDINGS: Seven key themes emerged describing the barriers and facilitators that
      the teams experienced during the pharmacist integration: (1) relationships, trust
      and respect; (2) pharmacist role definition; (3) orientation and support; (4)
      pharmacist personality and professional experience; (5) pharmacist presence and
      visibility; (6) resources and funding; and (7) value of the pharmacist role.
      Teams from urban and rural communities experienced some of these challenges in
      unique ways. CONCLUSIONS: Primary care teams that integrated a pharmacist
      experienced several common barriers and facilitators. The negative impact of
      these barriers can be mitigated with effective planning and support that is
      individualized for the type of community where the team is located.

PMID- 24279948
TI  - Comprehensive analysis of differentially expressed rice actin depolymerizing
      factor gene family and heterologous overexpression of OsADF3 confers Arabidopsis
      Thaliana drought tolerance.
AB  - BACKGROUND: Actin depolymerizing factors (ADFs) are small actin-binding proteins.
      Many higher-plant ADFs has been known to involve in plant growth, development and
      pathogen defense. However, in rice the temporal and spatial expression of OsADF
      gene family and their relationship with abiotic stresses tolerance is still
      unknown. RESULTS: Here we reported the first comprehensive gene expression
      profile analysis of OsADF gene family. The OsADF genes showed distinct and
      overlapping gene expression patterns at different growth stages, tissues and
      abiotic stresses. We also demonstrated that both OsADF1 and OsADF3 proteins were
      localized in the nucleus. OsADF1 and OsADF3 were preferentially expressed in
      vascular tissues. Under ABA or abiotic stress treatments, OsADF3::GUS activity
      was enhanced in lateral roots and root tips. Ectopically overexpressed OsADF3
      conferred the mannitol- and drought-stress tolerance of transgenic Arabidopsis
      seedlings by increasing germination rate, primary root length and survival.
      Several drought-tolerance responsive genes (RD22, ABF4, DREB2A, RD29A, PIP1; 4
      and PIP2; 6) were upregulated in transgenic Arabidopsis under drought stress.
      CONCLUSIONS: These results suggested that OsADF gene family may participate in
      plant abiotic stresses response or tolerance and would facilitate functional
      validation of other OsADF genes.

PMID- 24279949
TI  - [Sudden unexpected death in epilepsy: SUDEP].
AB  - Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy
      related cause of death. Patients with refractory epilepsy are at especially high
      risk of SUDEP. SUDEP occurs predominantly at night and unwitnessed, and can best
      be regarded as a fatal tonic-clonic seizure. While its pathophysiology is
      incompletely understood, SUDEP is most probably triggered by a number of
      predisposing and precipitating factors, including seizure-induced respiratory
      depression and cardiac arrhythmia. Achieving seizure freedom is the best way to
      prevent SUDEP. Nocturnal supervision may be another alternative preventive
      strategy, but this requires further research.

PMID- 24279950
TI  - [Terminal care in patients with amyotrophic lateral sclerosis].
AB  - Patients with amyotrophic lateral sclerosis (ALS) often fear of dying from
      suffocation. This fear is also common in relatives and caregivers. Research has,
      however, shown that ALS patients seldom die from suffocation. More than 90% of
      all ALS patients die peacefully. Death is mostly preceded by a peracute decrease
      in consciousness due to hypercapnia caused by alveolar hypoventilation.
      Mechanical ventilation, especially at night, can reduce the symptoms caused by
      hypoventilation. However, little by little, the effectiveness of ventilation may
      decrease to such an extent that it is no longer useful or desirable. Termination
      of long-standing ventilation requires careful preparation. Intensive guidance of
      the relevant medical, practical and ethical aspects are necessary. Particularly
      in the pre-terminal and terminal phases, support given to an ALS patient requires
      a pro-active attitude on the part of the treating physician. To this end,
      physicians may seek advice from the Dutch ALS Center, a palliative care
      consultation team, a hospice physician or a center for home mechanical
      ventilation.

PMID- 24279951
TI  - [New treatment options for infections with Clostridium difficile].
AB  - Currently available broad spectrum antibiotics are not sufficiently effective
      against recurrent Clostridium difficile infections (CDI). Donor faecal microbiota
      transplantation is a very effective treatment for second and recurrent infection
      but is time-consuming and requires careful screening of donors. The new narrow
      spectrum antibiotic fidaxomicin is a good alternative in a first CDI or a first
      recurrence, but treatment is expensive and there are no data on its effectiveness
      in a second or later recurrence. Fidaxomicin is less effective against infections
      caused by the Ribotype 027 strain, a virulent strain that is regularly
      encountered in the Netherlands. The effectiveness of various other promising
      narrow spectrum antibiotics is currently being investigated. Medications that
      support the gut flora or the immune system seem to offer new perspectives.
      Expectations for the currently available probiotic preparations and toxin binders
      are not high.

PMID- 24279952
TI  - [Concerns about residents' mental fitness: two possible strategies for a
      solution].
AB  - A good level of physical and mental fitness is essential in order to function
      optimally as a resident. Concerns about residents' mental fitness have recently
      been raised, based on high percentages of residents suffering from burnout and
      depression and data on the experience of stress and anxiety. Lack of mental
      fitness has negative consequences for the individual doctor as well as for the
      quality of patient care delivered. This is expressed in loss of empathy, delivery
      of suboptimal care and increased medical errors. Finding solutions for the lack
      of, or deterioration in, mental fitness is crucial. We discuss two potential
      strategies: (1) the removal or reduction of obstacles to residents' mental
      fitness and (2) the provision of resources to improve mental fitness. 

PMID- 24279953
TI  - [Harvey and his theory of circulation].
AB  - In 1628 the English physician William Harvey (1578-1657) published his
      revolutionary theory that blood circulates through the body driven by the heart.
      This challenged the long-standing teachings of Hippocrates and Galen concerning 4
      different bodily fluids or 'humours' that flowed through separate arterial and
      venous vascular systems. Harvey gained considerable influence in society as a
      member of the prestigious Royal College of Physicians in London and as personal
      physician to King James I and King Charles I. He strove for a more empirical
      foundation of medicine by means of anatomic demonstrations and vivisections.
      Despite enduring considerable criticism he managed to disseminate his ideas
      around the influential universities of Europe in the course of his lifetime.
      However, consequent changes in practice would not be brought about until decades
      after Harvey's death, when Galenist treatments such as blood-letting were
      gradually abandoned. 

PMID- 24279954
TI  - [Summary of the practice guideline 'Heavy menstrual bleeding'].
AB  - A new multidisciplinary practice guideline on heavy menstrual bleeding (HMB) has
      recently been published. HMB may occur with or without structural abnormalities.
      The pictorial blood loss assessment chart (PBAC) is the best method for
      estimating the amount of blood loss and for distinguishing between heavy and
      normal blood loss. Haemoglobin levels should be determined at least once.
      Transvaginal ultrasound is the preferred imaging technique. Saline or gel
      infusion sonography should be used in cases where ultrasound results are suspect
      for intracavitary abnormalities. A hysteroscopy should only be performed if
      sonography results are inconclusive. The very first treatment of choice should be
      placement of a hormone-impregnated intrauterine system. For HMB without
      structural abnormalities, endometrial ablation is an alternative to hysterectomy,
      whereby second-generation ablation techniques are preferred to first-generation
      techniques. For HMB with uterine fibroids, uterine artery embolisation is a good
      alternative to hysterectomy. For HMB with submucosal fibroids, hysteroscopic
      resection of the fibroids is recommended.

PMID- 24279955
TI  - [A pregnant woman with a blood vessel in the membrane].
AB  - In a 34-year-old woman with a dichorionic twin pregnancy, a velamentous insertion
      of the umbilical cord of the second twin was diagnosed with ultrasound. During
      caesarean section the second child was born within the membranes; the velamentous
      insertion was clearly visible. 

PMID- 24279956
TI  - Monitoring ship noise to assess the impact of coastal developments on marine
      mammals.
AB  - The potential impacts of underwater noise on marine mammals are widely
      recognised, but uncertainty over variability in baseline noise levels often
      constrains efforts to manage these impacts. This paper characterises natural and
      anthropogenic contributors to underwater noise at two sites in the Moray Firth
      Special Area of Conservation, an important marine mammal habitat that may be
      exposed to increased shipping activity from proposed offshore energy
      developments. We aimed to establish a pre-development baseline, and to develop
      ship noise monitoring methods using Automatic Identification System (AIS) and
      time-lapse video to record trends in noise levels and shipping activity. Our
      results detail the noise levels currently experienced by a locally protected
      bottlenose dolphin population, explore the relationship between broadband sound
      exposure levels and the indicators proposed in response to the EU Marine Strategy
      Framework Directive, and provide a ship noise assessment toolkit which can be
      applied in other coastal marine environments. 

PMID- 24279957
TI  - Climate change and emissions impacts on atmospheric PAH transport to the Arctic.
AB  - We investigate effects of 2000-2050 emissions and climate changes on the
      atmospheric transport of three polycyclic aromatic hydrocarbons (PAHs):
      phenanthrene (PHE), pyrene (PYR), and benzo[a]pyrene (BaP). We use the GEOS-Chem
      model coupled to meteorology from a general circulation model and focus on
      impacts to northern hemisphere midlatitudes and the Arctic. We project declines
      in anthropogenic emissions (up to 20%) and concentrations (up to 37%), with
      particle-bound PAHs declining more, and greater declines in midlatitudes versus
      the Arctic. Climate change causes relatively minor increases in midlatitude
      concentrations for the more volatile PHE and PYR (up to 4%) and decreases (3%)
      for particle-bound BaP. In the Arctic, all PAHs decline slightly under future
      climate (up to 2%). Overall, we observe a small 2050 "climate penalty" for
      volatile PAHs and "climate benefit" for particle-bound PAHs. The degree of
      penalty or benefit depends on competition between deposition and surface-to-air
      fluxes of previously deposited PAHs. Particles and temperature have greater
      impacts on future transport than oxidants, with particle changes alone accounting
      for 15% of BaP decline under 2050 emissions. Higher temperatures drive increasing
      surface-to-air fluxes that cause PHE and PYR climate penalties. Simulations
      suggest ratios of more-to-less volatile species can be used to diagnose signals
      of climate versus emissions and that these signals are best observed in the
      Arctic. 

PMID- 24279959
TI  - Commentary: why is the odds ratio for involvement in serious road traffic
      accident among drunk drivers in Norway and Finland higher than in other
      countries?
AB  - OBJECTIVE: Recent Norwegian and Finnish studies have found high odds ratios for
      serious or fatal injury in road traffic accidents among drivers after drinking
      alcohol. In this report we have compared the odds ratios with results from
      studies in other countries. METHODS: A literature review was conducted. RESULTS:
      The odds ratios were significantly higher than in countries where drunk driving
      is more common. CONCLUSION: The calculated odds ratios are not only related to
      alcohol use or blood alcohol concentration per se but also related to the study
      design-for example, the inclusion of nonculpable drivers among cases-and
      confounding factors not included in statistical analysis; for example, risk
      taking behavior. Those two issues may contribute to explaining why the reported
      odds ratios are higher for Norway and Finland.

PMID- 24279960
TI  - The reasons for the recent decline in young driver licensing in the United
      States.
AB  - OBJECTIVE: This survey examined why a substantial percentage of young adults
      currently do not have a driver's license and the future plans of this group
      concerning obtaining a license. METHOD: A questionnaire was developed to examine
      several issues related to an individual's decision not to obtain a driver's
      license. An online survey was conducted, yielding useable responses from 618
      persons aged 18 to 39 without a driver's license. RESULTS: The top 8 reasons for
      not having a driver's license were as follows: (1) too busy or not enough time to
      get a driver's license (determined by personal priorities), (2) owning and
      maintaining a vehicle is too expensive, (3) able to get transportation from
      others, (4) prefer to bike or walk, (5) prefer to use public transportation, (6)
      concerned about how driving impacts the environment, (7) able to communicate
      and/or conduct business online instead, and (8) disability/medical/vision
      problems. Of the respondents, 22% indicated that they plan to never obtain a
      driver's license. On the other hand, 69% expect to get a driver's license within
      the next 5 years. Young adults without a driver's license-in comparison with the
      general population of the same age-tend to have less education and higher
      unemployment. However, the present study was not designed to investigate whether
      there is a causal relationship or the direction of the effect if there were such
      a relationship.

PMID- 24279958
TI  - A transcriptomic approach to elucidate the physiological significance of human
      cytochrome P450 2S1 in bronchial epithelial cells.
AB  - BACKGROUND: Cytochrome P450 2S1 (CYP2S1) is an orphan P450 with an unknown
      biological function. Data from our laboratory and others suggest that CYP2S1 may
      have an important physiological role in modulating the synthesis and metabolism
      of bioactive lipids including prostaglandins and retinoids. CYP2S1 expression is
      elevated in multiple epithelial-derived cancers as well as in the chronic
      hyperproliferative disease psoriasis. Whether CYP2S1 expression in proliferative
      disease is protective, detrimental, or neutral to disease progression remains to
      be determined. Two human bronchial epithelial cells (BEAS-2B) were constructed to
      represent chronic depletion of CYP2S1 using short-hairpin RNA (shRNA) silencing
      directed toward the 3'UTR (759) and exon 3 (984) of the CYP2S1 gene and compared
      with a non-targeting shRNA control (SCRAM). Both CYP2S1 mRNA and protein were
      depleted by approximately 75% in stable cell lines derived from both targeted
      shRNA constructs (759 and 984). To elucidate the biological significance of
      CYP2S1, we analyzed transcriptome alterations in response to CYP2S1 depletion in
      human lung cells. RESULTS: RNA-sequencing (RNA-seq) analysis was performed to
      compare the transcriptome of the control (SCRAM) and the CYP2S1-depleted (759)
      BEAS-2B cell lines. Transcriptomes of the replicates from the two cell lines were
      found to be distinct populations as determined using Principal Component Analysis
      and hierarchical clustering. Approximately 1000 genes were differentially
      expressed in response to CYP2S1 depletion. Consistent with our previous
      phenotypes, DAVID analysis revealed altered regulation in key pathways implicated
      in cell proliferation and migration. Transcriptomic profiles were also consistent
      with the metabolism of proposed endogenous substrates. Pathway analysis also
      revealed significant expression changes within mTOR signaling, a critical pathway
      in cell growth. To determine whether these changes manifest as altered cell size,
      cell diameter and volume were calculated, revealing that CYP2S1 depletion
      promotes cell growth in BEAS-2B cells. CONCLUSIONS: These data suggest that
      pathway analysis of sequence-based gene expression is a powerful method to
      identify pathways and phenotypic alterations in response to changes in orphan
      enzyme expression. Our results suggest a novel role for CYP2S1-mediated
      metabolism in modulating BEAS-2B cell size. These findings warrant further
      studies on CYP2S1 regulated pathways to elucidate potential substrates of CYP2S1.

PMID- 24279961
TI  - Attitudes toward seat belt use and in-vehicle technologies for encouraging belt
      use.
AB  - OBJECTIVES: In-vehicle seat belt reminders and interlocks can encourage belt use,
      but widespread adoption of these features depends on the degree of acceptance
      among both belted and unbelted occupants. The current study collected information
      about attitudes toward belt use and in-vehicle technologies for encouraging belt
      use. METHODS: A national telephone survey of 1218 adult drivers and passengers
      was conducted using random samples of landline and cell phone numbers. Part-time
      belt users and nonusers were oversampled. All respondents were asked about
      frequency of belt use, buckling routines, and support for different types of belt
      interlocks. Part-time belt users and nonusers were queried in more depth about
      different types of reminders and reminder strategies. RESULTS: Almost all
      respondents said that they always use their seat belts (91%). Few said that they
      did not always (8%) or never (1%) used belts. Driving a short distance (67%),
      forgetting (60%), and comfort (47%) were common reasons why part-time belt users
      do not buckle up; comfort (77%), not needing a seat belt (54%), and disliking
      being told what to do (50%) were most frequently cited among nonusers. When asked
      about various types of belt interlocks, part-time belt users and nonusers most
      often said that ignition interlocks would make them more likely to buckle up (70%
      and 44%, respectively). However, only 44 to 51 percent of all respondents,
      including full-time belt users, supported using the different types of interlocks
      to increase belt use. A larger proportion of part-time belt users and nonusers
      said that they would be more likely to buckle up in response to auditory and
      haptic reminders than visual reminders. More than two thirds of part-time belt
      users and at least one third of nonusers said that they would be more likely to
      buckle up in response to belt reminders that become more intense or continue
      indefinitely; these reminders would be acceptable to about half of part-time belt
      users and around one fifth of nonusers. CONCLUSIONS: The Moving Ahead for
      Progress in the 21st Century (MAP-21) law allows the National Highway Traffic
      Safety Administration to strengthen minimum requirements for belt reminders or
      allow the use of interlocks to meet federal safety standards. Even though most
      people always buckle up, belt interlocks are supported by only about half of full
      time belt users and by fewer part-time belt users and nonusers. Enhanced reminder
      systems are more acceptable than belt interlocks and are viewed as almost as
      effective as interlocks if persistent enough. Supplemental materials are
      available for this article. Go to the publisher's online edition of Traffic
      Injury Prevention to view the supplemental file.

PMID- 24279962
TI  - A method for linking motor vehicle victim and collision data collected by
      multiple county agencies.
AB  - OBJECTIVE: This study assessed roadside and bedside factors associated with early
      mortality following motor vehicle trauma. METHODS: This retrospective cohort
      study evaluated motor vehicle crashes in Orange County Florida in 2009 that
      became medical examiner cases. Data from the Department of Highway Safety and
      Motor Vehicles (DHSMV), emergency medical services (EMS), a level I trauma
      center, and the medical examiner were integrated for the analysis. The primary
      outcome measure was early death, defined by death within 48 hours of a motor
      vehicle trauma. Both traditional and nontraditional predictors of early mortality
      were assessed. RESULTS: The most significant factors associated with early
      mortality were as follows: (1) From autopsy: hemothorax (odds ratio [OR] = 8.26,
      95% confidence interval [CI]: 1.83-37.3) and liver injury (OR = 4.26, 95% CI:
      1.70-15.6); (2) from hospital data: systolic blood pressure (OR = 0.98, 95% CI:
      0.96-0.99) and having cardiopulmonary resuscitation (CPR) performed in the
      emergency department (OR = 13.4, 95% CI: 1.51-118.72); and (3) from DHSMV:
      involvement of drugs and/or alcohol (OR = 4.27, 95% CI: 1.33-13.6), total
      fatalities (OR = 6.07, 95% CI: 1.57-23.5), speed of vehicle (OR = 1.06, 95% CI:
      1.02-1.09), and number of lanes at the crash scene (OR = 1.58, 95% CI: 1.13
      2.20). CONCLUSION: These results were made possible by integrating 4 distinct
      data sources. As future research in traffic-related injury moves toward
      prevention, it will be critical to evaluate new preventative strategies quickly
      and effectively. A unique number that is both patient and event specific that
      could be incorporated into each of these databases would make such integration
      seamless. Successful methods for linking data collected by the multiple agencies
      involved in motor vehicle collisions will ultimately provide invaluable
      information for medical personnel, researchers, engineers, planners, and policy
      makers at the local, state, and national levels to identify safety priorities to
      reduce crash-related injuries and fatalities.

PMID- 24279963
TI  - Road safety from the perspective of driver gender and age as related to the
      injury crash frequency and road scenario.
AB  - OBJECTIVE: The objective of this research is to develop safety performance
      functions (SPFs) on 2-lane rural roads to predict the number of injury crashes
      per year per 10(8) vehicles/km on the road segment using a study on the influence
      of the human factors (gender, age, number of drivers) and road scenario
      (combination of infrastructure and environmental conditions found at the site at
      the time of the crash) on the effects of a crash by varying the dynamic.
      Countermeasures are suggested to reduce the injury crash rate and include
      different awareness campaigns and structural measures on the segments of road.
      METHODS: An 8-year period was analyzed for which 5 years of crash information
      were used to calibrate and specify SPFs and the remaining 3 years were used to
      check the reliability of the equations. Before moving to the calibration phase, a
      technique to filter anomalous injury crash rates was adopted by using a method
      widely used in geotechnical engineering that is based on estimates of ranges of
      values that can be considered fluctuations of the "regular" measures compared to
      values estimated as "abnormal" for each homogeneous scenario. Due to
      overdispersion of crash data, generalized estimating equations and additional log
      linkage equation were adopted to calibrate SPFs. The Akaike information criterion
      and Bayesian information criterion were used to check the reliability of the
      models. RESULTS: Six SPFs were calibrated: for head-on/side collisions, one
      equation was built for circular curves and one for tangent segments; for rear-end
      collisions, one equation was built for daylight and one for the hours of
      darkness; for single-vehicle run-off-road crashes, one equation was built for wet
      road surface conditions and one for dry road surface conditions. An original
      numerical variable, SLEH, was designed to calibrate safety models reflecting the
      identified road surface (dry/wet), light conditions (day/night), geometric
      element (tangent segment/circular curve), and human factors (gender/age/number
      drivers) all together when the crash occurred, as provided by related police
      reports. The validation procedure succeeded. It emerged that males and females
      are involved in crashes of varying degrees of frequency, depending on the driving
      scenario that presents itself and the gender of the other drivers involved in the
      crash. Several different dangerous scenarios were identified: only female drivers
      on a dry road surface in daylight on tangent segments increased the risk for head
      on/side collisions; only male drivers on a wet road surface in daylight on
      circular curves increased the risk for single-vehicle crashes; and crashes
      involving both female and male drivers on a dry road surface in daylight on a
      circular curve increased the risk for head-on/side collisions. CONCLUSION:
      According to the current study, based on the network approach for the allocation
      of economic resources and planning of road safety strategies, calibration of
      injury crash rate prediction models for specific target collision type is
      important because of the range of harms that are caused by different collision
      types. From these studies it is apparent that the age and gender of drivers
      considered together further refines how those factors contribute to crashes.
      Countermeasures (structural road interventions and/or safety awareness campaigns)
      can be planned to reduce the highest rate of injury crash for each gender and
      road scenario: the awareness campaigns cannot be generalized or vague but must be
      organized by age and gender, because this study shows that crash dynamics alter
      as these factors change, with consideration for the varying psychological traits
      of the driver groups. Before-and-after safety evaluations can be used to check
      the safety benefits of improvements carried out on the roadways, within budget
      constraints for improvement or safety compliance investments for future
      operation. Supplemental materials are available for this article. Go to the
      publisher's online edition of Traffic Injury Prevention to view the supplemental
      file.

PMID- 24279964
TI  - Underreporting of road crashes in Pakistan and the role of fate.
AB  - OBJECTIVE: Comprehensive, accurate information about road crashes and related
      trauma is a prerequisite for identification and control of risk factors as well
      as for identifying faults within the broader road safety system. Quality data and
      appropriate crash investigation are critical in reducing the road toll that is
      rapidly growing in much of the developing world, including Pakistan. This
      qualitative research explored the involvement of social and cultural factors (in
      particular, fatalism) in risky road use in Pakistan. The findings highlight a
      significant issue, previously unreported in the road safety literature, namely,
      the link between fatalistic beliefs and inaccurate reporting of road crashes.
      METHOD: Thirty interviews (one-on-one) were conducted by the first author with
      police officers, drivers, policy makers, and religious orators in 3 Pakistani
      cities. FINDINGS: Evidence emerged of a strong link between fatalism and the
      underreporting of road crashes. In many cases, crashes and related road trauma
      appear to go unreported because a crash is considered to be one's fate and,
      therefore, beyond personal control. Fate was also implicated in the practice of
      reconciliation between parties after a crash without police involvement and the
      seeking and granting of pardon for a road death. CONCLUSIONS: These issues
      represent additional factors that can contribute to underreporting of crashes and
      associated trauma. Together, they highlight complications involved in
      establishing the true cost of road trauma in a country such as Pakistan and the
      difficulties faced when attempting to promote scientifically based road safety
      information to counteract faith-based beliefs.

PMID- 24279965
TI  - Side impact PMHS thoracic response with large-volume air bag.
AB  - OBJECTIVE: The objective of this study is to assess the response of postmortem
      human subjects (PMHS) to a large-volume side air bag in a fully instrumented and
      well-controlled side impact test condition. METHODS: Three adult male PMHS were
      subjected to right-side pure lateral impacts. Each stationary seated subject was
      struck at 4.3 +/- 0.1 m/s by a rigid wall installed on a 1700-kg rail-mounted
      sled. Each subject was held stationary by a system of tethers until immediately
      prior to being impacted by the moving wall. A large side air bag was mounted to
      the wall and deployed so that it was fully inflated at the time it contacted the
      subject's right side. The load wall consisted of an adjustable matrix of 15
      individual plates, each supported by a 5-axis load cell that recorded the
      interaction between the subject and impacting wall. Two-dimensional (external)
      torso deformation was provided by a chest band that encircled the torso at the
      level of the sixth rib laterally. Triaxial acceleration was measured at the head,
      spine, and sacrum via 3 orthogonal accelerometers mounted to the same bone
      mounted hardware that held the marker clusters used for kinematic analysis.
      RESULTS: Peak pelvic load normal to the wall averaged 6.8 kN, which was over 5
      times that recorded for the shoulder (1.3 kN) and the thorax (1.2 kN). Lateral
      chest deflection ranged from 9 to 21 mm. Two of the 3 subjects sustained 2 and 9
      fractures, respectively. CONCLUSIONS: Two of the 3 PMHS sustained rib fractures
      despite low levels of thorax deflection. We attribute this finding to individual
      variability in subject injury tolerance. Other response parameters exhibited
      lower levels of variability and characterize PMHS response to a potentially
      beneficial side impact countermeasure. Supplemental materials are available for
      this article. Go to the publisher's online edition of Traffic Injury Prevention
      to view the supplemental file.

PMID- 24279966
TI  - Optimization of vehicle deceleration to reduce occupant injury risks in frontal
      impact.
AB  - OBJECTIVE: In vehicle frontal impacts, vehicle acceleration has a large effect on
      occupant loadings and injury risks. In this research, an optimal vehicle crash
      pulse was determined systematically to reduce injury measures of rear seat
      occupants by using mathematical simulations. METHOD: The vehicle crash pulse was
      optimized based on a vehicle deceleration-deformation diagram under the
      conditions that the initial velocity and the maximum vehicle deformation were
      constant. Initially, a spring-mass model was used to understand the fundamental
      parameters for optimization. In order to investigate the optimization under a
      more realistic situation, the vehicle crash pulse was also optimized using a
      multibody model of a Hybrid III dummy seated in the rear seat for the objective
      functions of chest acceleration and chest deflection. A sled test using a Hybrid
      III dummy was carried out to confirm the simulation results. Finally, the optimal
      crash pulses determined from the multibody simulation were applied to a human
      finite element (FE) model. RESULTS: The optimized crash pulse to minimize the
      occupant deceleration had a concave shape: a high deceleration in the initial
      phase, low in the middle phase, and high again in the final phase. This crash
      pulse shape depended on the occupant restraint stiffness. The optimized crash
      pulse determined from the multibody simulation was comparable to that from the
      spring-mass model. From the sled test, it was demonstrated that the optimized
      crash pulse was effective for the reduction of chest acceleration. The crash
      pulse was also optimized for the objective function of chest deflection. The
      optimized crash pulse in the final phase was lower than that obtained for the
      minimization of chest acceleration. In the FE analysis of the human FE model, the
      optimized pulse for the objective function of the Hybrid III chest deflection was
      effective in reducing rib fracture risks. CONCLUSIONS: The optimized crash pulse
      has a concave shape and is dependent on the occupant restraint stiffness and
      maximum vehicle deformation. The shapes of the optimized crash pulse in the final
      phase were different for the objective functions of chest acceleration and chest
      deflection due to the inertial forces of the head and upper extremities. From the
      human FE model analysis it was found that the optimized crash pulse for the
      Hybrid III chest deflection can substantially reduce the risk of rib cage
      fractures. Supplemental materials are available for this article. Go to the
      publisher's online edition of Traffic Injury Prevention to view the supplemental
      file.

PMID- 24279967
TI  - Analysis of delta velocity and PDOF by means of collision partner and structural
      involvement in real-life crash pulses with modern passenger cars.
AB  - OBJECTIVE: In the widely used National Automotive Sampling System (NASS)
      Crashworthiness Data System (CDS) database, summary metrics that describe crashes
      are available. Crash angle or principal direction of force (PDOF) is estimated by
      the crash examiner and velocity changes (DeltaV) in the x- and y-directions are
      calculated by the WinSMASH computer program using PDOF and results from rigid
      barrier crash testing combined with deformations of the crashed car. In recent
      years, results from event data recorders (EDRs) have been added to the database.
      The aim of this study is to compare both PDOF and DeltaV between EDR measurements
      and WinSMASH calculations. METHODS: NASS-CDS inclusion criteria were model-year
      2000 through 2010 automobiles, frontal crashes with DeltaV higher than 16 km/h,
      and the pulse entirely recorded in the EDR module. This resulted in 649 cases.
      The subject vehicles were further examined and characterized with regard to
      frontal structure engagement (large or small overlap) as well as collision
      properties of the partner (impact location; front, side, or back) or object. The
      EDR crash angle was calculated as the angle between the lateral and longitudinal
      DeltaV at the time of peak longitudinal DeltaV. This angle was compared to the
      NASS-CDS investigator's estimated PDOF with regard to structural engagement and
      the collision partner or object. Multiple linear regression was used to establish
      adjustment factors on DeltaV and crash angle between the results calculated based
      on EDR recorded data and that estimated in NASS-CDS. RESULTS: According to this
      study, simulation in the newest WinSMASH version (2008) underestimates EDR DeltaV
      by 11 percent for large overlap crashes and 17 percent for small overlap impacts.
      The older WinSMASH version, used prior to 2008, underestimated each one of these
      two groups by an additional 7 percentage points. Another significant variable to
      enhance the prediction was whether the crash examiner had reported the WinSMASH
      estimated DeltaV as low or high. In this study, none of the collision partner
      groups was significantly different compared to front-to-front impacts. However,
      with a larger data set a couple of configurations may very well be significantly
      different. In this study, the crash angle denoted by PDOF in the NASS database
      underestimates the crash angle calculated from recent EDR modules by 35 percent.
      CONCLUSION: On average the DeltaV and crash angle are underestimated in NASS-CDS
      when analyzing the data based on collision partner/object and structural
      engagement. The largest difference is found in small overlap crashes and the
      least difference in collision scenarios similar to barrier tests. Supplemental
      materials are available for this article. Go to the publisher's online edition of
      Traffic Injury Prevention to view the supplemental file.

PMID- 24279968
TI  - Characterization of vertebral angle and torso depth by gender and age groups with
      a focus on occupant safety.
AB  - OBJECTIVE: The human body changes as it becomes older. The automotive safety
      community has been interested in understanding the effect of age on restraint
      performance. Focus has been placed on characterizing the body's structural
      changes associated with age and gender. In this study, spine alignment and torso
      depth were assessed, because both variables have been shown to affect injury
      risk. METHODS: The data was obtained from computed tomography (CT) scans of more
      than 24,000 patients aged 16 and older. The data consisted of thoracic and lumbar
      vertebral angles relative to a fixed plane, as well as vertebra-to-front skin and
      spine-to-back skin distances. Angle measurements were taken in the sagittal plane
      at each vertebra level from T1 to L5; distance measurements were taken from T6 to
      L5. The data were analyzed as a function of gender and age with the young group
      defined as 16 to 29 years old and the older group as 75 and up. RESULTS:
      Vertebral angles were different depending on location. They varied from -24.5 +/-
      8.9 degrees  at T2 to 12.2 +/- 5.6 degrees  at L1. The vertebral angles also
      varied with age. Angles in the older male group were 1.74 times larger at T1 and
      2.03 times larger at T7 than in the young male group. Similar findings were
      observed for females. The effect of age and gender was modeled with
      forward/backward selection using a regression model. The vertebra-to-front skin
      distance also differed depending on vertebral level. It was highest at T10 at
      162.5 +/- 30.9 mm and lowest at L4 at 125.3 +/- 37.3 mm for the entire study
      population. On average, males had larger distances than females. The spine-to
      back distances were greatest in the lumbar area. The spine-to-back distance
      increased with lower vertebral level, regardless of age. The vertebral angle and
      distance data were analyzed for a male subgroup approximating the height and
      weight of a 50th percentile male dummy. The results showed that the vertebra-to
      front skin distance increased with age. There was not a clear trend for the spine
      to-back skin distance and L1 vertebral angle. CONCLUSIONS: The changes in the
      vertebral angles, as well as the anterior and posterior spine-to-skin distances
      along the sagittal plane, were determined as a function of age and gender. The
      effect was greatest in the mid-thoracic area. Spine alignment and body shape
      differences need to be considered in human mathematical models used to develop
      safety countermeasures for the older population, because they may affect the
      loading path and lead to different seating postures or belt positioning.
      Supplemental materials are available for this article. Go to the publisher's
      online edition of Traffic Injury Prevention to view the supplemental file.

PMID- 24279969
TI  - Risk factors related to fatal truck crashes on Korean freeways.
AB  - OBJECTIVES: The major purpose of this study was to identify risk factors
      affecting truck crashes on freeways and propose recommendations for safer truck
      traffic operations. METHODS: Truck crashes were analyzed to identify how truck
      traffic safety is related to prevailing traffic and weather conditions.
      Prevailing traffic conditions were characterized by central tendencies and the
      spatiotemporal variation of traffic parameters collected from freeway traffic
      surveillance systems. A total of 377 truck crashes occurring on Korean freeways
      in a recent 3-year period, 2008-2010, were analyzed together with corresponding
      prevailing traffic conditions and weather conditions. Several statistical tests
      were conducted to understand the characteristics of prevailing traffic conditions
      before crash occurrence based on different weather conditions. In addition, a
      binary logistic regression technique was applied to identify causal factors
      affecting truck crash severity under normal and adverse weather conditions.
      RESULTS: Major findings from the analyses are discussed with truck operations
      strategies including speed enforcement, variable speed limit, and truck lane
      restriction from the safety enhancement point of view. Speed-related variables
      representing prevailing traffic conditions before crash occurrences were found to
      be the most statistically significant factors affecting truck crash severity,
      compared to volume-related variables such as the volume-to-capacity ratio (v/c).
      It is inferred that speed management is an effective tool for safer truck traffic
      operations on freeways. The major findings can be further discussed to derive
      valuable insights into truck traffic operations based on different weather
      conditions, such as normal and adverse. CONCLUSIONS: Some recommendations for
      safer truck traffic operations were presented based on the results obtained. The
      outcomes of this study could be effectively utilized to support the development
      of various traffic operations strategies and policies for truck traffic safety.
      Supplemental materials are available for this article. Go to the publisher's
      online edition of Traffic Injury Prevention to view the supplemental file.

PMID- 24279970
TI  - Bicycle crashes in different riding environments in the Australian capital
      territory.
AB  - INTRODUCTION: Cyclists are increasingly overrepresented in traffic crash
      casualties in Australia. There is evidence that better cycling infrastructure
      increases participation, but whether it reduces the numbers of injured cyclists
      is less clear. This study examined injury outcomes of crashes in different
      cycling environments. METHODS: Adult cyclists injured on- and off-road were
      recruited from emergency departments from November 2009 to May 2010 in the
      Australian Capital Territory. Eligible participants (n = 313/372, 84.1%) were
      interviewed and their injury self-reports were corroborated with medical records
      where available. Participants who had crashed in transport-related areas (n =
      202, 64.5%) are the focus of this article. RESULTS: Participants had crashed in
      traffic (39.1%), in cycle lanes (7.9%), on shared paths (36.1%), and on footpaths
      (16.8%). Based on average weekly traffic counts, the crash involvement rate per
      1000 cyclists was 11.8 on shared paths compared to 5.8 on cycle lanes. Over half
      of the participants (52.0%) were injured in single-vehicle bicycle crashes. The
      remainder involved other road users, including motor vehicles (20.8%), other
      bicycles (18.8%), pedestrians (6.4%), and animals (2.0%). Pedestrians were
      involved in 16.4 percent of crashes on shared paths. Minor injuries (Abbreviated
      Injury Scale [AIS] 1) were sustained by 58.4 percent of cyclists, moderately
      severe injuries (AIS 2) were sustained by 36.1 percent of cyclists, and 5.4
      percent of cyclists were seriously injured (AIS 3+). The average treatment
      required was 1.8 days with 7.5 days off work and cost to the cyclist of $869
      excluding medical treatment. Cyclists who crashed on shared paths or in traffic
      had higher injury severity scores (ISS; 4.4, 4.0) compared to those in cycle
      lanes or on footpaths (3.3, 3.4) and required more treatment days (2.8, 1.7
      versus 0.0, 0.2). CONCLUSIONS: Fewer cyclists were injured in on-road cycle lanes
      than in other cycling environments, and a high proportion of injuries were
      incurred on shared paths. This study highlights an urgent need to determine
      appropriate criteria and management strategies for paths classified as suitable
      for shared or segregated usage. Supplemental materials are available for this
      article. Go to the publisher's online edition of Traffic Injury Prevention to
      view the supplemental files.

PMID- 24279971
TI  - Safety evaluation for expressways: a comparative study for macroscopic and
      microscopic indicators.
AB  - OBJECTIVE: This article is to assess the performance of 3 macroscopic safety
      indicators (speed, speed dispersion, and volume) and two microscopic potential
      crash risks (time to collision and deceleration rate to avoid crash) on safety
      evaluation for expressways. METHODS: Field data were collected at 3 locations for
      4 different time periods on an expressway in Beijing, China. The speed of each
      vehicle, headway time, and vehicle length were recorded by a traffic management
      system. The 5 safety indicators were thus calibrated on the basis of the
      collected data. Further, consistency and comparative analyses were applied to
      assess the performance of indicators. RESULTS: According to the analyses, speed
      dispersion was a better predictor of the two microscopic potential risks compared
      to the two macroscopic indicators. CONCLUSIONS: Speed dispersion is recommended
      to proactively assess road safety because (1) it provides consistent risk
      evaluation with microscopic potential risks and (2) it makes data collection
      easier.

PMID- 24279972
TI  - Agricultural vehicles and rural road safety: tackling a persistent problem.
AB  - OBJECTIVE: Crashes involving agricultural vehicles (AVs) on public roads are an
      increasing road safety problem. We aim to analyze developments in the appearance
      and severity of these accidents, identify influencing factors, and draw lessons
      for possible interventions for accident prevention within the context of modern
      mechanized agriculture. METHODS: To analyze developments in the appearance of
      accidents we use a subset of accidents with AVs involved on public roads in The
      Netherlands aggregated per year for 1987-2010. To identify and explore preventive
      measures we use an in-depth study of the Dutch Safety Board. With a study of
      international literature we put our findings in a wider context. RESULTS: During
      this time span, Dutch annual averages show 15 registered fatal accidents
      involving AVs, 93 with hospitalization and 137 with slight injuries. For nonfatal
      accidents, the numbers are decreasing over time. This decrease is proportionate
      to the reduction in the total number of traffic victims. For fatalities, however,
      the number is stable, increasing its proportion in all traffic fatalities from 1
      in 1987 to 2 percent in 2010. Related to the number of inhabitants, this number
      is 2 times the value in the UK and 3 times the value in the United States.
      Influencing factors can be related to the 3 road system components (AV, driver,
      and infrastructure). Weak points for AVs are the view from the driver's seat,
      visibility at night, permitted vehicle width, and crash aggressivity (large
      kinetic energy of the AV) that is transferred to other road users in case of a
      collision. Important factors identified for the driver are poor risk perception
      and high risk acceptance, in combination with speeding, dysfunctional use such as
      the use of AVs as modes of transport to and from school, and driving on public
      roads without protecting or removing protruding and sharp components. For
      infrastructure, the focus is on road design and separation of AVs from other
      motor vehicles. Lessons to be learned follow from these accident factors. For AV
      drivers, a driver's training focusing on driving behavior in the presence of
      vulnerable road users and concluding with an examination is advised. For vehicle
      safety, actual practice in The Netherlands is inadequate for control of proper
      maintenance. Some permanent requirements for the AV are insufficiently specific
      (view) or effective (lighting) and too generous (width). For infrastructure, a
      wide range of measures is available. CONCLUSIONS: A targeted approach to all road
      system components is urgently needed to avoid a further worsening of existing
      problems and to reduce the above proportional role of AVs in road danger.
      Supplemental materials are available for this article. Go to the publisher's
      online edition of Traffic Injury Prevention to view the supplemental file.

PMID- 24279973
TI  - Exploring the impact of access designs on crash injury severity on multilane
      highways.
AB  - OBJECTIVE: Access design is a critical factor that influences the safety and
      mobility of urban/suburban multilane highways due to the interactions between
      access movements and through traffic. An effective way for improving the safety
      and mobility of multilane highways is to control access maneuvers by implementing
      appropriate access designs. Understanding the impact of access designs on crash
      injury severity is beneficial for implementing effective countermeasures to
      mitigate crash injury at access points. Thus, the objectives of this article are
      to investigate the impact of access designs on crash injury severity and identify
      contributing factors of crash injury severity at access points of multilane
      highways. METHODS: A total of 1830 crash records were collected at 149 access
      points with different access designs for a period of 3 years (2008-2010) in
      Florida. A heterogeneous logit model, relaxing the constraint of identical
      variances across observations in the traditional ordered choice models, was
      developed to evaluate the impact of access designs on crash injury severity and
      identify contributing factors. The marginal effects of the developed model were
      used to interpret the impact of access designs and other contributing factors.
      RESULTS: At 4-leg access points, given that a crash has occurred, replacing full
      median openings with closed medians will reduce the probability of severe injury
      (fatality, incapacitating injury, or nonincapacitating injury) by 9.73 percent;
      substituting full median openings with directional median openings will reduce
      the probability of severe injury by 11.02 percent. At 3-leg access points, given
      that a crash has occurred, closed medians significantly experience a lower risk
      of severe injury than full median openings; however, there is no evidence that
      directional median openings are similarly effective. Other contributing factors
      of crash injury severity at access points were identified as number of lanes,
      shoulder width, median width, driveway density, left-turn bay on major roads,
      speed limit, average annual daily traffic (AADT), high-density residential area,
      daylight, driver age, and truck involvement. CONCLUSIONS: Installation of
      directional median openings is a reasonable safety treatment at 4-leg access
      points because this access design has better safety performance than full median
      openings in terms of crash injury severity; in addition, it provides fewer
      restrictions on accessibility than closed medians. Other effective treatments
      include installing left-turn storage bays at median openings and increasing the
      width of shoulders and medians. Supplemental materials are available for this
      article. Go to the publisher's online edition of Traffic Injury Prevention to
      view the supplemental file.

PMID- 24279975
TI  - Development of a novel prediction method of cis-elements to hypothesize
      collaborative functions of cis-element pairs in iron-deficient rice.
AB  - BACKGROUND: Cis-acting elements are essential genomic sequences that control gene
      expression. In higher eukaryotes, a series of cis-elements function
      cooperatively. However, further studies are required to examine the co-regulation
      of multiple cis-elements on a promoter. The aim of this study was to propose a
      model of cis-element networks that cooperatively regulate gene expression in rice
      under iron (Fe) deficiency. RESULTS: We developed a novel clustering-free method,
      microarray-associated motif analyzer (MAMA), to predict novel cis-acting elements
      based on weighted sequence similarities and gene expression profiles in
      microarray analyses. Simulation of gene expression was performed using a support
      vector machine and based on the presence of predicted motifs and motif pairs. The
      accuracy of simulated gene expression was used to evaluate the quality of
      prediction and to optimize the parameters used in this method. Based on sequences
      of Oryza sativa genes upregulated by Fe deficiency, MAMA returned experimentally
      identified cis-elements responsible for Fe deficiency in O. sativa. When this
      method was applied to O. sativa subjected to zinc deficiency and Arabidopsis
      thaliana subjected to salt stress, several novel candidate cis-acting elements
      that overlap with known cis-acting elements, such as ZDRE, ABRE, and DRE, were
      identified. After optimization, MAMA accurately simulated more than 87% of gene
      expression. Predicted motifs strongly co-localized in the upstream regions of
      regulated genes and sequences around transcription start sites. Furthermore, in
      many cases, the separation (in bp) between co-localized motifs was conserved,
      suggesting that predicted motifs and the separation between them were important
      in the co-regulation of gene expression. CONCLUSIONS: Our results are suggestive
      of a typical sequence model for Fe deficiency-responsive promoters and some
      strong candidate cis-elements that function cooperatively with known cis
      elements.

PMID- 24279976
TI  - Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child.
AB  - Deep vein thrombosis (DVT) is a rare disease in pediatric patients. We report a
      pediatric patient who developed DVT in association with methicillin-resistant
      Staphylococcus aureus (MRSA) bacteremia complicated with septic arthritis,
      osteomyelitis, and myositis extensively. It is crucial to consider
      musculoskeletal infection associated with DVT in any child who presents with
      severe swollen limbs and limitations of motion. Prompt antibiotic and
      anticoagulant treatments should be initiated to reduce the risk of fatal
      complications.

PMID- 24279977
TI  - Malignant renal tumors in childhood: report of 54 cases treated at a single
      institution.
AB  - BACKGROUND: Wilms tumor is the most common primary renal malignancy occurring in
      childhood. Significant improvement has been made in the treatment of children
      with Wilms tumor. However, the treatment of patients with non-Wilms renal tumors
      remains challenging. METHODS: Between 1991 and 2010, 70 children with renal
      tumors were diagnosed at a single institution. Fifty-four patients were
      histologically confirmed and divided into three groups, including 42 Wilms
      tumors, seven clear cell sarcomas of kidney, and five malignant rhabdoid tumors.
      Most patients underwent unilateral nephrectomy and lymph node sampling followed
      by adjuvant chemotherapy. Twenty-one of these patients subsequently received
      radiotherapy. RESULTS: During follow-up, 12 patients died of progressive disease
      and one died of operative mortality. One patient with unilateral pleural
      metastases subsequently underwent hematopoietic stem cell transplantation. The
      median survival time of all patients was 88 months. Children under 2 years of age
      at diagnosis with Wilms tumor or clear cell sarcoma of kidney had an excellent
      survival rate of 100% compared to the 0% survival rate of MRT. CONCLUSION:
      Younger age at diagnosis bore a better prognosis than did older age, whereas a
      diagnosis of malignant rhabdoid tumor portended a worse prognosis. Younger
      patients and appropriate treatment may have contributed to the improved prognosis
      of clear cell sarcoma of kidney.

PMID- 24279978
TI  - Gender differences revealed by the Brief Illness Perception Questionnaire in
      allergic rhinitis.
AB  - BACKGROUND: The increasing prevalence of allergic rhinitis (AR) is reported
      worldwide. Illness perception (IP) assessment is warranted in current routine
      clinical practice to assist communication between patients and medical staff, and
      improve adherence to treatment and disease outcome. OBJECTIVE: To investigate a
      group of patients with AR in terms of their IP by the Brief Illness Perception
      Questionnaire (BIPQ) and to correlate the findings with demographic and clinical
      features. METHODS: In this observational questionnaire-based study, a successive
      series of patients treated for AR at the Allergology and Immunology Teaching
      Hospital, Clinical Centre of Serbia in Belgrade, were enrolled from September
      2010 to January 2011, and 93 valid questionnaires were analyzed. Each item of the
      BIPQ assessed one dimension of IP like the consequences, timeline, personal
      control, treatment control, identity, coherence, emotional representation and
      concern. RESULTS: The patients' average age: 35.25 +/- 12.42; male/female ratio:
      0.79; the overall BIPQ score = 34.69 +/- 11.89. The highest item-related scores
      were found for treatment control (8.17 +/- 2.28), illness understanding (7.34 +/-
      2.96) and emotional representation (6.30 +/- 3.45), and the lowest for identity
      (4.8 +/- 2.78) and affection (4.83 +/- 2.65). Women compared with men perceive AR
      as a significantly more threatening disease (P = 0.04). No significant
      correlation between the BIPQ total or item-related scores was found for any other
      demographic or clinical feature. CONCLUSION: The BIPQ, which allows rapid
      assessment of IP and reveals gender differences in AR, is a convenient tool for
      use in routine clinical practice. Further investigation is needed to demonstrate
      how IP may influence patients' behavior in AR, treatment adherence and disease
      outcome.

PMID- 24279979
TI  - Accidental death involving professional fireworks.
AB  - An interesting case of accidental death involving the explosion of professional
      fireworks in an apartment is described. The examination of the scene permitted to
      study several effects of the explosion on walls, ceiling, furniture and
      especially on a balcony where the victim was found. The external examination of
      the victim showed extensive thermal injuries, degloving injuries and extensive
      shrapnel wounds. The autopsy examination showed subarachnoid haemorrhage
      localized to the cerebellum, haemorrhage in the soft tissues of the neck and
      chest and fracture of one clavicle. Almost the entire surface of lungs showed
      blunt injuries and the liver showed tearing of parenchyma and multiple cavities.
      Histological analysis were carried out showing thickening of alveolar septae,
      enlargement of alveolar spaces and alveolar ruptures in lung sections while
      numerous, round, empty spaces were detected in the parenchyma of the liver. The
      examination of the scene and of the fragments found showed that at least eight
      pyrotechnical charges exploded on the balcony, in close proximity of the
      threshold with the living room of the apartment. According to the chemical
      findings, the charges were typical for professional use and were filled with a
      mixture of potassium perchlorate and aluminium. A conservative calculation
      results in more than 1.5 kg total mass of pyrotechnic composition exploding very
      close to the victim.

PMID- 24279981
TI  - Ultrarapid formation of homogeneous Cu6Sn5 and Cu3Sn intermetallic compound
      joints at room temperature using ultrasonic waves.
AB  - Homogeneous intermetallic compound joints are demanded by the semiconductor
      industry because of their high melting point. In the present work, ultrasonic
      vibration was applied to Cu/Sn foil/Cu interconnection system at room temperature
      to form homogeneous Cu6Sn5 and Cu3Sn joints. Compared with other studies based on
      transient-liquid-phase soldering, the processing time of our method was
      dramatically reduced from several hours to several seconds. This ultrarapid
      intermetallic phase formation process resulted from accelerated interdiffusion
      kinetics, which can be attributed to the sonochemical effects of acoustic
      cavitation at the interface between the liquid Sn and the solid Cu during the
      ultrasonic bonding process. 

PMID- 24279980
TI  - Reduction-responsive polymeric micelles and vesicles for triggered intracellular
      drug release.
AB  - SIGNIFICANCE: The therapeutic effects of current micellar and vesicular drug
      formulations are restricted by slow and inefficient drug release at the
      pathological site. The development of smart polymeric nanocarriers that release
      drugs upon arriving at the target site has received a tremendous amount of
      attention for cancer therapy. RECENT ADVANCES: Taking advantage of a high
      reducing potential in the tumor tissues and in particular inside the tumor cells,
      various reduction-sensitive polymeric micelles and vesicles have been designed
      and explored for triggered anticancer drug release. These reduction-responsive
      nanosystems have demonstrated several unique features, such as good stability
      under physiological conditions, fast response to intracellular reducing
      environment, triggering drug release right in the cytosol and cell nucleus, and
      significantly improved antitumor activity, compared to traditional reduction
      insensitive counterparts. CRITICAL ISSUES: Although reduction-sensitive micelles
      and polymersomes have accomplished rapid intracellular drug release and enhanced
      in vitro antitumor effect, their fate inside the cells including the mechanism,
      site, and rate of reduction reaction remains unclear. Moreover, the systemic fate
      and performance of reduction-sensitive polymeric drug formulations have to be
      investigated. FUTURE DIRECTIONS: Biophysical studies should be carried out to
      gain insight into the degradation and drug release behaviors of reduction
      responsive nanocarriers inside the tumor cells. Furthermore, novel ligand
      decorated reduction-sensitive nanoparticulate drug formulations should be
      designed and explored for targeted cancer therapy in vivo.

PMID- 24279982
TI  - Sonication effects on non-radical reactions. A sonochemistry beyond the
      cavitation?
AB  - The kinetics of pH-independent hydrolysis of 4-methoxyphenyl dichloroacetate were
      investigated under ultrasonic irradiation with an application of 10% of the
      maximum power of the equipment and without sonication in acetonitrile-water
      binary mixtures with a content of acetonitrile ranging from 0.008 to 35 wt.%.
      Similar kinetic investigations were performed at intensities corresponding to
      10%, 20%, 30%, 40%, and 50% of the input energy in solvent mixtures containing 10
      wt.% and 25 wt.% acetonitrile. In parallel, the responses of KI and terephthalic
      acid dosimeters at applied irradiation levels were registered under the same
      experimental conditions. Significant kinetic sonication effects were found at
      sound intensities presumably not inducing cavitation in the solution. This result
      provides an experimental evidence of kinetic effects of ultrasound in the absence
      of cavitation. A disturbing impact of cavitation on the ultrasonic acceleration
      of the reaction was found. The implications of these findings were discussed.

PMID- 24279983
TI  - Memory consolidation for duration.
AB  - Humans and animals encode and store in memory elapsed intervals as evidenced
      through their temporal expectancies. However, there are very few experimental
      studies on long-term memory of duration. The aim of this original study was to
      examine the consolidation process for duration and its effect on time judgement.
      In our study, memory of duration was tested in humans with a temporal
      generalization task. Consolidation was assessed by means of a 15-min nontemporal
      interference task introduced at different delays after the initial learning of a
      4-s standard duration. The results showed that (a) when tested 24 hours after the
      learning phase, memory of the 4-s duration was disrupted (less precision and
      lengthening effect) if the interference task was introduced 30-45 min after
      learning; (b) no disruption was observed when memory was tested immediately after
      the interference task; and (c) there was a temporal gradient of the disruptive
      interference effect within the first hour after learning. Overall, these results
      fulfil the key criteria for the inference of a synaptic/cellular consolidation
      process and thus demonstrate that, as is the case for other memories, memory of
      duration undergoes a consolidation process that lasts at least one hour.

PMID- 24279984
TI  - Tubeless percutaneous nephrolithotomy without losing the possibility of second
      look nephroscopy: The perfect combination.
AB  - OBJECTIVES: To evaluate an alternative approach to tubeless surgery that allows a
      second percutaneous procedure using the same nephrostomy tract. METHODS: Twenty
      patients underwent percutaneous nephrolithotomy from September 2012 to May 2013
      at our institution. Inclusion criteria were: absence of urinary infection, single
      puncture and operative time less than 2 h. Following the procedure the initially
      placed ureteral catheter was exteriorized through the working sheath by tying a
      non-absorbable suture to its end. On postoperative day 1 all patients were
      studied with non-enhanced CT or X-ray film. If the patient was rendered stone
      free, the stent was removed along with the urethro-vesical catheter. If a
      residual stone was present, we recovered the ureteral catheter and used the same
      nephrostomy tract for a second endoscopic procedure. Patients were assessed for
      pain, postoperative complications, length of stay, stone free rate, hematocrit
      and creatinine variations. RESULTS: Thirteen patients met the inclusion criteria.
      No major complications related to the stent placement and its exteriorization
      were seen. Two patients required a second percutaneous procedure successfully
      achieved recovering the ureteral catheter through the nephrostomy tract.
      CONCLUSION: We present a safe and simple modification of tubeless percutaneous
      nephrolithotomy, with its well-known clinical benefits but maintaining a safe
      path for an eventual second look procedure if necessary.

PMID- 24279985
TI  - The dog as a trigger factor of allergy liquid semen.

PMID- 24279987
TI  - Highly reversible Mg insertion in nanostructured Bi for Mg ion batteries.
AB  - Rechargeable magnesium batteries have attracted wide attention for energy
      storage. Currently, most studies focus on Mg metal as the anode, but this
      approach is still limited by the properties of the electrolyte and poor control
      of the Mg plating/stripping processes. This paper reports the synthesis and
      application of Bi nanotubes as a high-performance anode material for rechargeable
      Mg ion batteries. The nanostructured Bi anode delivers a high reversible specific
      capacity (350 mAh/gBi or 3430 mAh/cm(3)Bi), excellent stability, and high
      Coulombic efficiency (95% initial and very close to 100% afterward). The good
      performance is attributed to the unique properties of in situ formed,
      interconnected nanoporous bismuth. Such nanostructures can effectively
      accommodate the large volume change without losing electric contact and
      significantly reduce diffusion length for Mg(2+). Significantly, the
      nanostructured Bi anode can be used with conventional electrolytes which will
      open new opportunities to study Mg ion battery chemistry and further improve its
      properties. 

PMID- 24279988
TI  - Functional analyses of an E3 ligase gene AIP2 from wheat in Arabidopsis revealed
      its roles in seed germination and pre-harvest sprouting.
AB  - Pre-harvest sprouting (PHS) seriously affects wheat yield and quality of the
      grain. ABI3 is a key factor in the activation of seed development and repression
      of germination in Arabidopsis. An ABI3-interacting protein (AIP2) could
      polyubiquitinate ABI3, impair seed dormancy and promote seed germination in
      Arabidopsis. In this study, two wheat AIP2 genes, TaAIP2A and TaAIP2B, were
      isolated. Subcellular localization assay and yeast two-hybrid analysis revealed
      that TaAIP2A and TaAIP2B may function through interaction with wheat Viviporous-1
      (TaVp1). The transcripts TaAIP2A and TaAIP2B were more abundant in wheat PHS
      susceptible cultivars than that of resistant ones, and decreased gradually
      following seed development. Expression of TaAIP2A and TaAIP2B in Arabidopsis aip2
      1 mutant lines resulted in earlier flowering, promotion of seed germination, and
      reduced ABA sensitivity, respectively, somehow mimicking the phenotype of the
      wild type, with TaAIP2B having a stronger role in these aspects. Furthermore, the
      expression of upstream genes ABI1 and ABI2 were upregulated, whereas that of
      downstream genes ABI3 and ABI5 were downregulated in both TaAIP2A and TaAIP2B
      complemented lines upon ABA treatment. These results suggested that wheat AIP2s
      could negatively regulate the ABA signaling pathway and play important roles in
      seed germination, and thus wheat PHS resistance finally. 

PMID- 24279986
TI  - Deficiency of metabolic regulator FGFR4 delays breast cancer progression through
      systemic and microenvironmental metabolic alterations.
AB  - BACKGROUND: Endocrine FGF21 and FGF19 target adipocytes and hepatocytes through
      betaKlotho (KLB) and FGFR tyrosine kinases effecting glucose, lipid and energy
      metabolism. Both factors alleviate obesity and metabolic abnormalities which are
      contributing factors to breast tumor progression. Genomic manipulation of hepatic
      FGFR4 has uncovered roles of endocrine FGF signaling in both metabolic and
      cellular homeostasis. Here we determined whether systemic and microenvironmental
      metabolic alterations caused by the FGFR4 deficiency affect tumorigenesis in
      breast where FGFR4 is negligible. Breast tumors were induced in the bigenic mice
      with ablation of FGFR4 and overexpression of TGFalpha that activates Her2 in the
      ductal and lobular epithelium surrounded by adipocytes. Mammary tumorigenesis and
      alterations in systemic and breast microenvironmental metabolic parameters and
      regulatory pathways were analyzed. RESULTS: Ablation of FGFR4 had no effect on
      cellular homeostasis and Her2 activity of normal breast tissue. However, the
      absence of FGFR4 reduced TGFalpha-driven breast tumor incidence and progression
      and improved host survival. Notable increases in hepatic and serum FGF21, ileal
      FGF15/19, adiponectin and adipsin, and decreases in systemic Fetuin A, IGF-1,
      IGFBP-1, RBP4 and TIMP1 were observed. The ablation affected adipogenesis and
      secretory function of adipocytes as well as lipogenesis, glycolysis and energy
      homeostasis associated with the functions of mitochondria, ER and peroxisomes in
      the breast and tumor foci. Treatment with a chemical inhibitor of NAMPT involved
      in the pathways inhibited the growth and survival of breast tumor cells and tumor
      initiating cell-containing spheres. The FGFR4 ablation also caused elevation of
      inflammatory factors in the breast. CONCLUSIONS: Although the primary role of
      FGFR4 in metabolism occurs in hepatocytes, its ablation results in a net
      inhibitory effect on mammary tumor progression. We suggest that the tumor
      delaying effect of FGFR4 deficiency may be in large part due to elevated anti
      obesogenic FGF21 that triggers tumor-suppressing signals from both peripheral and
      breast adipocytes. The predominant changes in metabolic pathways suggested roles
      of metabolic effects from both peripheral and breast adipocytes on metabolic
      reprogramming in breast epithelial cells that contribute to the suppression of
      tumor progression. These results provide new insights into the contribution of
      systemic and microenvironmental metabolic effects controlled by endocrine FGF
      signaling to breast carcinogenesis.

PMID- 24279989
TI  - Second-sphere interactions between the C93-Y157 cross-link and the substrate
      bound Fe site influence the O2 coupling efficiency in mouse cysteine dioxygenase.
AB  - Cysteine dioxygenase (CDO) is a non-heme iron enzyme that catalyzes the O2
      dependent oxidation of l-cysteine (l-Cys) to produce cysteinesulfinic acid (CSA).
      Adjacent to the Fe site of CDO is a covalently cross-linked cysteine-tyrosine
      pair (C93-Y157). While several theories have been proposed for the function of
      the C93-Y157 pair, the role of this post-translational modification remains
      unclear. In this work, the steady-state kinetics and O2/CSA coupling efficiency
      were measured for wild-type CDO and selected active site variants (Y157F, C93A,
      and H155A) to probe the influence of second-sphere enzyme-substrate interactions
      on catalysis. In these experiments, it was observed that both kcat and the O2/CSA
      coupling efficiency were highly sensitive to the presence of the C93-Y157 cross
      link and its proximity to the substrate carboxylate group. Complementary electron
      paramagnetic resonance (EPR) experiments were performed to obtain a more detailed
      understanding of the second-sphere interactions identified in O2/CSA coupling
      experiments. Samples of the catalytically inactive substrate-bound Fe(III)-CDO
      species were treated with cyanide, resulting in a low-spin (S = 1/2) ternary
      complex. Remarkably, both the presence of the C93-Y157 pair and interactions with
      the Cys carboxylate group could be readily identified by perturbations to the
      rhombic EPR signal. Spectroscopically validated active site quantum
      mechanics/molecular mechanics and density functional theory computational models
      are provided to suggest a potential role for Y157 in the positioning of the
      substrate Cys in the active site and to verify the orientation of the g-tensor
      relative to the CDO Fe site molecular axis.

PMID- 24279990
TI  - Discovery of potent and efficacious cyanoguanidine-containing nicotinamide
      phosphoribosyltransferase (Nampt) inhibitors.
AB  - A co-crystal structure of amide-containing compound (4) in complex with the
      nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling
      were utilized to design and discover a potent novel cyanoguanidine-containing
      inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50=2.5nM, A2780 cell
      proliferation IC50=9.7nM). Further SAR exploration identified several additional
      cyanoguanidine-containing compounds with high potency and good microsomal
      stability. Among these, compound 15 was selected for in vivo profiling and
      demonstrated good oral exposure in mice. It also exhibited excellent in vivo
      antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model.
      The co-crystal structure of this compound in complex with the NAMPT protein was
      also determined. 

PMID- 24279991
TI  - Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia
      dactylomela with significant in vitro anti-neuroinflammatory activity.
AB  - A new regular diterpene possessing an unusual 1,6-anti-3-methylcyclohex-2-en-1-ol
      ring system, dactyloditerpenol acetate (1), has been extracted from the tropical
      sea hare Aplysia dactylomela and its stereostructure elucidated by spectroscopic
      methods. The absolute configuration of 1 was determined as 1S, 6S, 7R, 10S, and
      11R by application of Kishi's method for the assignment of absolute configuration
      of alcohols. The new diterpene potently inhibited in vitro thromboxane B2 (TXB2)
      (IC50 0.4MUM) and superoxide anion (O2(-)) (IC50 1MUM) generation from
      Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with
      concomitant low short-term toxicity. 

PMID- 24279992
TI  - Capturing enveloped viruses on affinity grids for downstream cryo-electron
      microscopy applications.
AB  - Electron microscopy (EM), cryo-electron microscopy (cryo-EM), and cryo-electron
      tomography (cryo-ET) are essential techniques used for characterizing basic virus
      morphology and determining the three-dimensional structure of viruses. Enveloped
      viruses, which contain an outer lipoprotein coat, constitute the largest group of
      pathogenic viruses to humans. The purification of enveloped viruses from cell
      culture presents certain challenges. Specifically, the inclusion of host-membrane
      derived vesicles, the complete destruction of the viruses, and the disruption of
      the internal architecture of individual virus particles. Here, we present a
      strategy for capturing enveloped viruses on affinity grids (AG) for use in both
      conventional EM and cryo-EM/ET applications. We examined the utility of AG for
      the selective capture of human immunodeficiency virus virus-like particles,
      influenza A, and measles virus. We applied nickel-nitrilotriacetic acid lipid
      layers in combination with molecular adaptors to selectively adhere the viruses
      to the AG surface. This further development of the AG method may prove essential
      for the gentle and selective purification of enveloped viruses directly onto EM
      grids for ultrastructural analyses. 

PMID- 24279993
TI  - Endosperm-specific expression of human acid beta-glucosidase in a waxy rice.
AB  - BACKGROUND: The deficiency of human acid beta-glucosidase (hGCase) causes Gaucher
      disease, a rare genetically-inherited disorder currently treated by enzyme
      replacement therapy using recombinant CHO-derived GCase. In an attempt to provide
      an alternative and more efficient production system, a chimeric cDNA coding for
      hGCase operatively linked to the signal peptide of rice glutelin 4 (GluB4) was
      put under the control of the GluB4 endosperm-specific promoter and inserted into
      the genome of a waxy rice. RESULTS: Molecular, immunological and biochemical
      analyses showed that recombinant hGCase, targeted to the protein storage vacuoles
      of rice endosperm cells, is equivalent to the native protein and has a
      glycosylation pattern compatible with direct therapeutic use. Compared to a
      previous study carried out on transgenic tobacco seeds, enzyme contents per unit
      of biomass were drastically increased; in addition, differently from what
      observed in tobacco, rice seed viability was unaffected by hGCase even at the
      highest production level. Transgenic seed polishing combined with a pretreatment
      of seed flour greatly facilitated hGCase extraction and purification with an
      industrially-scalable procedure. CONCLUSIONS: This study opens up the possibility
      to efficiently produce in the rice seed pharmaceutical compounds which are
      available in limited amounts or completely excluded from clinical practice due to
      the inadequacy of their production systems.

PMID- 24279994
TI  - Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis.
AB  - BACKGROUND: Desmoid tumours/aggressive fibromatosis (DT/AF) are infrequent soft
      tissue neoplasms. They usually behave as indolent diseases. However, they may
      grow locally infiltrating or compressing adjacent structures. The role of local
      treatment is limited and only a few drugs have shown activity. CASES
      PRESENTATION: We report the outcome of two patients affected by progressive DT/AF
      treated with the angiogenesis inhibitor pazopanib in two different institutions.
      Both patients achieved dramatic improvement in their symptoms and radiological
      signs of response. The clinical benefit lasted for more than 1 year and it is
      still ongoing. CONCLUSIONS: Pazopanib is an active treatment in DT/AF. It is the
      first time this has been reported.

PMID- 24279995
TI  - Coffee consumption and total mortality: a meta-analysis of twenty prospective
      cohort studies.
AB  - Coffee consumption has been shown to be associated with various health outcomes,
      but no comprehensive review and meta-analysis of the association between coffee
      consumption and total mortality has been conducted. To quantitatively assess this
      association, we conducted a meta-analysis of prospective cohort studies. Eligible
      studies were identified by searching the PubMed and EMBASE databases for all
      articles published through June 2013 and reviewing the reference lists of the
      retrieved articles. Pooled relative risks (RR) with 95% CI were calculated using
      a random-effects model. We identified twenty studies of coffee consumption and
      total mortality, including 129,538 cases of deaths among the 973,904
      participants. The RR of total mortality for the high v. low category of coffee
      consumption was 0.86 (95% CI 0.80, 0.92). The pooled RR for studies using >= 2-4
      cups/d as a cut-off for the high category was similar to that for studies using
      >= 5-9 cups/d as the cut-off. By geographical region, the inverse association
      tended to be stronger for the eight studies conducted in Europe (RR 0.78, 95% CI
      0.70, 0.88) and three studies carried out in Japan (RR 0.82, 95% CI 0.73, 0.92)
      than for the nine studies conducted in the USA (RR 0.92, 95% CI 0.84, 1.00). The
      inverse association was similar for men (RR 0.81, 95% CI 0.73, 0.90) and women
      (RR 0.84, 95% CI 0.79, 0.89). A weak, but significant, inverse association was
      found with moderate coffee consumption (1-2 cups/d; RR 0.92, 95% CI 0.87, 0.98).
      High decaffeinated coffee consumption was also found to be associated with a
      lower risk of death, but the data are limited. Our findings indicate that coffee
      consumption is associated with a reduced risk of total mortality.

PMID- 24279996
TI  - Larval pufferfish protected by maternal tetrodotoxin.
AB  - Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin. All
      species of the genus Takifugu accumulate TTX in the liver and ovaries, although
      the tissue(s) in which it is localized can differ among species. TTX is the major
      defense strategy the pufferfish appears to use against predators. TTX is also
      used as a male-attracting pheromone during spawning. Here we demonstrate an
      additional (and unexpected) use of maternal TTX in the early larval stages of the
      Takifugu pufferfish. Predation experiments demonstrated that juveniles of all the
      species of fish used as predators ingested pufferfish larvae, but spat them out
      promptly. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) analysis
      revealed that the pufferfish larvae contain a small quantity of TTX, which is not
      enough to be lethal to the predators. Immunohistochemical analysis with anti-TTX
      monoclonal antibody revealed that the TTX is primarily localized in the body
      surface of the larvae as a layer of protection. Our study showed the female
      parent of the Takifugu pufferfish vertically transfers TTX to the larvae through
      its accumulation in the ovaries, and subsequent localization on the body surface
      of the larvae. 

PMID- 24279997
TI  - Gene expression profile analysis of Ligon lintless-1 (Li1) mutant reveals
      important genes and pathways in cotton leaf and fiber development.
AB  - Ligon lintless-1 (Li1) is a monogenic dominant mutant of Gossypium hirsutum
      (upland cotton) with a phenotype of impaired vegetative growth and short lint
      fibers. Despite years of research involving genetic mapping and gene expression
      profile analysis of Li1 mutant ovule tissues, the gene remains uncloned and the
      underlying pathway of cotton fiber elongation is still unclear. In this study, we
      report the whole genome-level deep-sequencing analysis of leaf tissues of the Li1
      mutant. Differentially expressed genes in leaf tissues of mutant versus wild-type
      (WT) plants are identified, and the underlying pathways and potential genes that
      control leaf and fiber development are inferred. The results show that
      transcription factors AS2, YABBY5, and KANDI-like are significantly
      differentially expressed in mutant tissues compared with WT ones. Interestingly,
      several fiber development-related genes are found in the downregulated gene list
      of the mutant leaf transcriptome. These genes include heat shock protein family,
      cytoskeleton arrangement, cell wall synthesis, energy, H2O2 metabolism-related
      genes, and WRKY transcription factors. This finding suggests that the genes are
      involved in leaf morphology determination and fiber elongation. The expression
      data are also compared with the previously published microarray data of Li1 ovule
      tissues. Comparative analysis of the ovule transcriptomes of Li1 and WT reveals
      that a number of pathways important for fiber elongation are enriched in the
      downregulated gene list at different fiber development stages (0, 6, 9, 12, 15,
      18dpa). Differentially expressed genes identified in both leaf and fiber samples
      are aligned with cotton whole genome sequences and combined with the genetic fine
      mapping results to identify a list of candidate genes for Li1.

PMID- 24279998
TI  - Expression, SNV identification, linkage disequilibrium, and combined genotype
      association analysis of the muscle-specific gene CSRP3 in Chinese cattle.
AB  - The cysteine and glycine-rich protein 3 (CSRP3) plays an important role in the
      myofiber differentiation. Here, we identified five SNVs in all exon and intron
      regions of the CSRP3 gene using DNA sequencing, PCR-RFLP and forced-PCR-RFLP
      methods in 554 cattle. Four of the five SNVs were significantly associated with
      growth performance and carcass traits of the cattle. In addition, we evaluated
      haplotype frequency and linkage disequilibrium coefficient of five sequence
      variants. The result of haplotype analysis demonstrated 28 haplotypes present in
      Qinchuan and two haplotypes in Chinese Holstein. Only haplotypes 1 and 8 were
      being shared by two populations, haplotype 14 had the highest haplotype frequency
      in Qinchuan (17.4%) and haplotype 8 had the highest haplotype frequency in
      Chinese Holstein (94.4%). Statistical analyses of combined genotypes indicated
      that some combined genotypes were significantly or highly significantly
      associated with growth and carcass traits in the Qinchuan cattle population. qPCR
      analyses also showed that bovine CSRP3 gene was exclusively expressed in
      longissimus dorsi muscle and heart tissues. The data support the high potential
      of the CSRP3 as a marker gene for the improvement of growth performance and
      carcass traits in selection programs. 

PMID- 24279999
TI  - Array CGH characterization of an unbalanced X-autosome translocation associated
      with Xq27.2-qter deletion, 11q24.3-qter duplication and Xq22.3-q27.1 duplication
      in a girl with primary amenorrhea and mental retardation.
AB  - We present array comparative genomic hybridization (aCGH) characterization of an
      unbalanced X-autosome translocation with an Xq interstitial segmental duplication
      in a 16-year-old girl with primary ovarian failure, mental retardation, attention
      deficit disorder, learning difficulty and facial dysmorphism. aCGH analysis
      revealed an Xq27.2-q28 deletion, an 11q24.3-q25 duplication, and an inverted
      duplication of Xq22.3-q27.1. The karyotype was 46,X,der(X)t(X;11)(q27.2;q24.3)
      dup(X)(q27.1q22.3). We discuss the genotype-phenotype correlation in this case.
      Our case provides evidence for an association of primary amenorrhea and mental
      retardation with concomitant unbalanced X-autosome translocation and X chromosome
      rearrangement. 

PMID- 24280000
TI  - Determination of the photolysis rate coefficient of monochlorodimethyl sulfide
      (MClDMS) in the atmosphere and its implications for the enhancement of SO2
      production from the DMS + Cl2 reaction.
AB  - In this work, the photolysis rate coefficient of CH3SCH2Cl (MClDMS) in the lower
      atmosphere has been determined and has been used in a marine boundary layer (MBL)
      box model to determine the enhancement of SO2 production arising from the
      reaction DMS + Cl2. Absorption cross sections measured in the 28000-34000 cm(-1)
      region have been used to determine photolysis rate coefficients of MClDMS in the
      troposphere at 10 solar zenith angles (SZAs). These have been used to determine
      the lifetimes of MClDMS in the troposphere. At 0 degrees  SZA, a photolysis
      lifetime of 3-4 h has been obtained. The results show that the photolysis
      lifetime of MClDMS is significantly smaller than the lifetimes with respect to
      reaction with OH (~ 4.6 days) and with Cl atoms (~ 1.2 days). It has also been
      shown, using experimentally derived dissociation energies with supporting quantum
      chemical calculations, that the dominant photodissocation route of MClDMS is
      dissociation of the C-S bond to give CH3S and CH2Cl. MBL box modeling
      calculations show that buildup of MClDMS at night from the Cl2 + DMS reaction
      leads to enhanced SO2 production during the day. The extra SO2 arises from
      photolysis of MClDMS to give CH3S and CH2Cl, followed by subsequent oxidation of
      CH3S.

PMID- 24280001
TI  - A new route to alpha-carbolines based on 6pi-electrocyclization of indole-3
      alkenyl oximes.
AB  - Indoles are converted into alpha-carbolines in four steps by acylation at C-3,
      Boc-protection, olefination of the resulting 3-indolyl aldehydes or ketones to
      give N-Boc-3-indolyl alkenyl oxime O-methyl ethers, which upon heating to 240 
      degrees C under microwave irradiation undergo loss of the Boc-group, and 6pi
      electrocyclization to alpha-carbolines, following aromatization by loss of
      methanol (11 examples, 30-90% yield). 

PMID- 24280002
TI  - Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval
      impairment in rats.
AB  - The present study was designed to investigate the involvement of GABA-A receptors
      of the basolateral amygdala (BLA) in the impairing effect of acute stress on
      memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated
      and memory retrieval was measured in a step-through type passive avoidance
      apparatus. Acute stress was evoked by placing the animals on an elevated platform
      for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min
      stress, but not 10 min, before memory retrieval testing (pre-test exposure to
      stress) decreased the step-through latency, indicating stress-induced memory
      retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist,
      muscimol (0.005-0.02 MUg/rat), 5 min before exposure to an ineffective stress (10
      min exposure to stress) induced memory retrieval impairment. It is important to
      note that pre-test intra-BLA microinjection of the same doses of muscimol had no
      effect on memory retrieval in the rats unexposed to 10 min stress. The blockade
      of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5
      MUg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory
      retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline
      (0.4-0.5 MUg/rat) in rats unexposed to 20 min stress had no effect on memory
      retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 MUg/rat, intra
      BLA) reversed muscimol (0.02 MUg/rat, intra-BLA)-induced potentiation on the
      effect of stress in passive avoidance learning. It can be concluded that pre-test
      exposure to stress can induce memory retrieval impairment and the BLA GABA-A
      receptors may be involved in stress-induced memory retrieval impairment. 

PMID- 24280003
TI  - Denatured state ensembles with the same radii of gyration can form significantly
      different long-range contacts.
AB  - Defining the structural, dynamic, and energetic properties of the unfolded state
      of proteins is critical for an in-depth understanding of protein folding, protein
      thermodynamics, and protein aggregation. Here we analyze long-range contacts and
      compactness in two apparently fully unfolded ensembles of the same protein: the
      acid unfolded state of the C-terminal domain of ribosomal protein L9 in the
      absence of high concentrations of urea as well as the urea unfolded state at low
      pH. Small angle X-ray scattering reveals that the two states are expanded with
      values of Rg differing by <7%. Paramagnetic relaxation enhancement (PRE) nuclear
      magnetic resonance studies, however, reveal that the acid unfolded state samples
      conformations that facilitate contacts between residues that are distant in
      sequence while the urea unfolded state ensemble does not. The experimental PRE
      profiles for the acid unfolded state differ significantly from these predicted
      using an excluded volume limit ensemble, but these long-range contacts are
      largely eliminated by the addition of 8 M urea. The work shows that expanded
      unfolded states can sample very different distributions of long-range contacts
      yet still have similar radii of gyration. The implications for protein folding
      and for the characterization of unfolded states are discussed. 

PMID- 24280004
TI  - Temporal profiling of primary metabolites under chilling stress and its
      association with seedling chilling tolerance of rice (Oryza sativa L.).
AB  - BACKGROUND: Chilling stress is a major factor limiting rice production. Rice
      genotypes differ greatly in their seedling chilling tolerance (CT), which is
      known to involve differential expression of large numbers of genes and proteins.
      To further understand the metabolomic responses of rice to chilling stress,
      profiles of the 106 primary metabolites of a CT japonica variety,
      Lijiangxintuanhegu (LTH) and a chilling sensitive indica line, IR29, were
      investigated under a time-series of chilling stress and non-stress control
      conditions at the seedling stage. RESULTS: We identified 106 primary metabolites
      that were temporally and genotype-dependently regulated in LTH and IR29 under the
      time-series chilling stress and subsequent recovery. Three major groups of
      primary metabolites, amino acids (AAs), organic acids (OAs) and sugars, showed
      distinct change patterns in both genotypes in response to the chilling stress: a
      more general accumulation of most AAs, more dramatic decreased levels of most
      OAs, and greatly reduced levels for most sugars at early time points of stress
      but increased levels of specific sugars at the later time points of stress.
      Compared to IR29, LTH had more metabolites showing chilling induced changes,
      greater levels of these metabolomic changes and a greater ability to recover
      after stress, implying that LTH used a positive energy-saving strategy against
      chilling stress. During subsequent recovery, more metabolites were significantly
      and exclusively up-regulated in LTH, indicating their positive role in chilling
      tolerance. A comparative analysis of these metabolites data and differentially
      expressed genes data allowed identification of 7 AAs and related genes that were
      both chilling responsive and contributed greatly to the CT of LTH. CONCLUSIONS:
      The metabolomic responses of rice to chilling stress at the seedling stage were
      dynamic and involved large numbers of the metabolites. The chilling induced
      changes of three major groups of metabolites, AAs, OAs and sugars, in rice were
      well coordinated. The high level seedling CT of LTH was apparently attributed to
      its increased levels of most AAs and reduced energy consumption that resulted in
      increased glycolysis and strong resilience on recovery. The results of this study
      extend our understanding of molecular mechanisms of chilling stress tolerance in
      rice.

PMID- 24280006
TI  - Salivary proteins of plant-feeding hemipteroids - implication in phytophagy.
AB  - Many hemipteroids are major pests and vectors of microbial pathogens, infecting
      crops. Saliva of the hemipteroids is critical in enabling them to be voracious
      feeders on plants, including the economically important ones. A plethora of
      hemipteroid salivary enzymes is known to inflict stress in plants, either by
      degrading the plant tissue or by affecting their normal metabolism. Hemipteroids
      utilize one of the following three strategies of feeding behaviour: salivary
      sheath feeding, osmotic-pump feeding and cell-rupture feeding. The last strategy
      also includes several different tactics such as lacerate-and-flush, lacerate-and
      sip and macerate-and-flush. Understanding hemipteroid feeding mechanisms is
      critical, since feeding behaviour directs salivary composition. Saliva of the
      Heteroptera that are specialized as fruit and seed feeders, includes cell
      degrading enzymes, auchenorrhynchan salivary composition also predominantly
      consists of cell-degrading enzymes such as amylase and protease, whereas that of
      the Sternorhyncha includes a variety of allelochemical-detoxifying enzymes.
      Little is known about the salivary composition of the Thysanoptera. Cell
      degrading proteins such as amylase, pectinase, cellulase and pectinesterase
      enable stylet entry into the plant tissue. In contrast, enzymes such as
      glutathione peroxidase, laccase and trehalase detoxify plant chemicals, enabling
      the circumvention of plant-defence mechanisms. Salivary enzymes such as M1-zinc
      metalloprotease and CLIP-domain serine protease as in Acyrthosiphon pisum
      (Aphididae), and non-enzymatic proteins such as apolipophorin, ficolin-3-like
      protein and 'lava-lamp' protein as in Diuraphis noxia (Aphididae) have the
      capacity to alter host-plant-defence mechanisms. A majority of the hemipteroids
      feed on phloem, hence Ca++-binding proteins such as C002 protein, calreticulin
      like isoform 1 and calmodulin (critical for preventing sieve-plate occlusion) are
      increasingly being recognized in hemipteroid-plant interactions. Determination of
      a staggering variety of proteins shows the complexity of hemipteroid saliva:
      effector proteins localized in hemipteran saliva suggest a similarity to the
      physiology of pathogen-plant interactions. 

PMID- 24280005
TI  - Sterol regulatory element binding protein-dependent regulation of lipid synthesis
      supports cell survival and tumor growth.
AB  - BACKGROUND: Regulation of lipid metabolism via activation of sterol regulatory
      element binding proteins (SREBPs) has emerged as an important function of the
      Akt/mTORC1 signaling axis. Although the contribution of dysregulated Akt/mTORC1
      signaling to cancer has been investigated extensively and altered lipid
      metabolism is observed in many tumors, the exact role of SREBPs in the control of
      biosynthetic processes required for Akt-dependent cell growth and their
      contribution to tumorigenesis remains unclear. RESULTS: We first investigated the
      effects of loss of SREBP function in non-transformed cells. Combined ablation of
      SREBP1 and SREBP2 by siRNA-mediated gene silencing or chemical inhibition of
      SREBP activation induced endoplasmic reticulum (ER)-stress and engaged the
      unfolded protein response (UPR) pathway, specifically under lipoprotein-deplete
      conditions in human retinal pigment epithelial cells. Induction of ER-stress led
      to inhibition of protein synthesis through increased phosphorylation of
      eIF2alpha. This demonstrates for the first time the importance of SREBP in the
      coordination of lipid and protein biosynthesis, two processes that are essential
      for cell growth and proliferation. SREBP ablation caused major changes in lipid
      composition characterized by a loss of mono- and poly-unsaturated lipids and
      induced accumulation of reactive oxygen species (ROS) and apoptosis. Alterations
      in lipid composition and increased ROS levels, rather than overall changes to
      lipid synthesis rate, were required for ER-stress induction.Next, we analyzed the
      effect of SREBP ablation in a panel of cancer cell lines. Importantly, induction
      of apoptosis following SREBP depletion was restricted to lipoprotein-deplete
      conditions. U87 glioblastoma cells were highly susceptible to silencing of either
      SREBP isoform, and apoptosis induced by SREBP1 depletion in these cells was
      rescued by antioxidants or by restoring the levels of mono-unsaturated fatty
      acids. Moreover, silencing of SREBP1 induced ER-stress in U87 cells in
      lipoprotein-deplete conditions and prevented tumor growth in a xenograft model.
      CONCLUSIONS: Taken together, these results demonstrate that regulation of lipid
      composition by SREBP is essential to maintain the balance between protein and
      lipid biosynthesis downstream of Akt and to prevent resultant ER-stress and cell
      death. Regulation of lipid metabolism by the Akt/mTORC1 signaling axis is
      required for the growth and survival of cancer cells.

PMID- 24280007
TI  - Desmoplastic small round cell tumour: characteristics and prognostic factors of
      41 patients and review of the literature.
AB  - BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare but frequently
      fatal sarcoma, and many of its characteristics still require further
      clarification. METHODS: We retrospectively analysed 41 patients treated at or
      referred to two regional referral centres in the UK between 1991 and 2012. A
      review of the current literature was also performed. RESULTS: The median age of
      presentation was 27 years (range 16 to 45 years), with a male-to-female ratio of
      3:1. Ninety percent of patients had disease in the abdomen. The median size of
      the presenting tumour was 13 cm (range 3.5 to 23 cm), and 80% had metastatic
      disease at diagnosis, mainly in the liver (33%) and lungs (21%). Time-to
      progression (TTP) was 3.9, 2.3 and 1.1 months after first-, second- and third
      line chemotherapy, respectively. First-line treatment with VIDE chemotherapy
      appeared to confer the longest TTP (median 14.6 months). Ifosfamide and
      doxorubicin resulted in TTP of >3.8 months when used in any-line setting. Eleven
      patients received targeted agents as part of a clinical trial. After a median
      follow-up of 14 months, the overall median survival (MS) was 16 months. There was
      no difference in MS with regards to age, gender, or size of the presenting
      tumour. Patients with extra-abdominal disease survived longer compared to those
      with tumours in the abdomen (all still alive vs MS of 15 months; P = 0.0246).
      Patients with non-metastatic intra-abdominal disease who underwent surgery had an
      MS of 47 months (16 months for those who did not have surgery; P = 0.0235).
      Radiotherapy for locoregional control in patients with metastatic intra-abdominal
      DSRCT was associated with longer survival (MS of 47 vs 14 months; P = 0.0147).
      CONCLUSIONS: DSRCT is a rare but often fatal disease that mainly affects younger
      male patients. Those with intra-abdominal DSRCT have a poorer prognosis, although
      surgical resection for localised disease and radiotherapy in the metastatic
      setting are associated with improved survival. A patient's age, gender and size
      of presenting tumour do not have prognostic significance.

PMID- 24280008
TI  - OsRap2.6 transcription factor contributes to rice innate immunity through its
      interaction with Receptor for Activated Kinase-C 1 (RACK1).
AB  - BACKGROUND: The rice small GTPase OsRac1 is a molecular switch in rice innate
      immunity. The Receptor for Activated Kinase C-1 (RACK1) interacts with OsRac1 to
      suppress the growth of the rice blast fungus, Magnaporthe oryzae. RACK1 has two
      homologs in rice, RACK1A and RACK1B. Overexpressing RACK1A enhances resistance to
      the rice blast fungus. However, RACK1A downstream signals are largely unknown.
      RESULTS: Here, we report the identification of OsRap2.6, a transcription factor
      that interacts with RACK1A. We found a 94% similarity between the OsRap2.6 AP2
      domain and Arabidopsis Rap2.6 (AtRap2.6). Bimolecular fluorescence
      complementation (BiFC) assays in rice protoplasts using tagged OsRap2.6 and
      RACK1A with the C-terminal and N-terminal fragments of Venus (Vc/Vn) indicated
      that OsRap2.6 and RACK1A interacted and localized in the nucleus and the
      cytoplasm. Moreover, OsRap2.6 and OsMAPK3/6 interacted in the nucleus and the
      cytoplasm. Expression of defense genes PAL1 and PBZ1 as well as OsRap2.6 was
      induced after chitin treatment. Disease resistance analysis using OsRap2.6 RNAi
      and overexpressing (Ox) plants infected with the rice blast fungus indicated that
      OsRap2.6 RNAi plants were highly susceptible, whereas OsRap2.6 Ox plants had an
      increased resistance to the compatible blast fungus. CONCLUSIONS: OsRap2.6
      contributes to rice innate immunity through its interaction with RACK1A in
      compatible interactions.

PMID- 24280009
TI  - Screening for dementia and other causes of cognitive impairment in general
      hospital in-patients.

PMID- 24280010
TI  - Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological
      target of behavioural sensitization to morphine in rats.
AB  - Drug addiction is a major public health issue, yet the underlying adaptation of
      neural networks by drugs of abuse is not fully understood. We have previously
      linked chaperone heat shock protein 70 (Hsp70) to drug-induced adaptations.
      Focusing on the NAc core and shell, the present study aims to provide further
      findings for our understanding of the relation between behavioural sensitization
      to morphine and Hsp70 at transcriptional and functional levels in rats. Firstly,
      we delineated the characteristics of behavioural sensitization induced by a
      single morphine exposure (1-10 mg/kg, s.c.). Secondly, Hsp70 protein expression
      in the NAc core was time- and dose-relatedly induced during the development of
      behavioural sensitization to a single morphine exposure in rats, and Pearson
      analysis indicated a positive correlation between behavioural sensitization and
      Hsp70 expression in NAc core. Thirdly, at the transcriptional level, intra-NAc
      core injection of the specific heat shock factor-I (HSF-I) inhibitor N-Formyl-3,4
      methylenedioxy-benzylidine-gamma-butyrolactam (KNK437) suppressed Hsp70
      expression and the development of behavioural sensitization, while the HSF-I
      specific inducer geranylgeranylacetone (GGA) promoted both of them.
      Interestingly, intra-NAc shell injection of KNK437 or GGA did not affect the
      development of behavioural sensitization. Finally, both the functional inhibition
      of Hsp70 ATPase activity by methylene blue (MB), and the antagonism of Hsp70
      substrate binding site (SBD) activity by pifithrin-MU (PES) impaired the
      development of behavioural sensitization when they were microinjected into the
      NAc core. Taken together, the critical involvement of chaperone Hsp70 in
      behavioural sensitization to morphine identifies a biological target for long
      lasting adaptations with relevance to addiction.

PMID- 24280011
TI  - Passenger protein determines translocation versus retention in the endoplasmic
      reticulum for aromatase expression.
AB  - Aromatase protein is overexpressed in the breasts of women affected with cancer.
      In the endoplasmic reticulum (ER), signal sequence and signal anchors (SAs)
      facilitate translocation and topology of proteins. To understand the function of
      type-I SAs (SA-Is), we evaluated translocation of aromatase, whose signal anchor
      follows a hydrophilic region. Aromatase SA-I mediates translocation of a short N
      terminal hydrophillic domain to ER lumen and integrates the protein in the
      membrane, with the remainder of the protein residing in the cytosol. We showed
      that lack of a signal peptidase cleavage site is not responsible for the stop
      transfer function of SA-I. However, SA-I could not block the translocation of a
      full-length microsomal secretory protein and was cleaved as part of the signal
      sequence. We propose that interaction between the translocon and the region after
      the signal anchor plays a critical role in directing the topology of the protein
      by SA-Is. The positive charges in the signal sequence helped it to override the
      function of signal anchor. Thus, when signal sequence follows SA-I immediately,
      the interaction with the translocon is perturbed and topology of the protein in
      ER is altered. If signal sequence is placed far enough from SA-I, then it does
      not affect membrane integration of SA-I. In summary, we conclude that it is not
      just the SA-I, but also the region following it, which together affect function
      of aromatase SA-I in ER. 

PMID- 24280012
TI  - Cloning and characterization of goose interleukin-17A cDNA.
AB  - Interleukin-17 (IL-17 or IL-17A) is a proinflammatory cytokine produced by
      activated T cells. IL-17A plays important roles in inflammation and host defense.
      In this study, the cDNA of the goose IL-17A (GoIL-17A) gene was cloned from
      thymocytes. Recombinant GoIL-17A (rGoIL-17A) was expressed using a baculovirus
      expression system and then biologically characterized. The complete open reading
      frame (ORF) of GoIL-17A contains 510 base pairs that encode 169 amino acid
      residues, including a 29-amino acid signal peptide and a single potential N
      linked glycosylation site. This protein has a molecular weight of 18.9kDa. The
      amino acid sequence showed 95.9%, 84.6%, 45.0% and 38.4% similarity with the
      corresponding duck, chicken, rat, and human IL-17A sequences, respectively. The
      six conserved cysteine residues were also observed in GoIL-17A. A recombinant,
      mature form of GoIL-17A was produced and its biological activities in goose
      embryonic fibroblasts were investigated. RT-PCR analysis revealed a marked up
      regulation of IL-6 and IL-8 mRNA expression in goose embryonic fibroblasts
      treated with 1-50 MUg of rGoIL-17A for 12h. The GoIL-17A gene sequence and the
      biologically active recombinant protein may be useful for understanding the role
      of IL-17A in immune regulation.

PMID- 24280013
TI  - Copper-catalyzed oxidative decarboxylative couplings of sulfoximines and aryl
      propiolic acids.
AB  - A method has been developed for the preparation of N-alkynylated sulfoximines
      involving the copper-catalyzed decarboxylative coupling of sulfoximines with aryl
      propiolic acids. A range of substituents on both the sulfoximidoyl moiety and the
      aryl group of the propiolic acid were compatible with this reaction process to
      afford a series of sulfoximidoyl-functionalized alkynes. 

PMID- 24280014
TI  - [Experience of a falls prevention unit in an intermediate care hospital].
AB  - INTRODUCTION: The aim of this study is to determine clinical features and
      interventions in patients attended in our hospital falls prevention unit.
      MATERIAL AND METHODS: Medical records and evaluation protocols from October 2010
      to June 2012 were reviewed. Results are expressed in means and standard
      deviation. RESULTS: We studied 68 patients: 53 came due to falls (77.9%), and 15
      (22%) due to gait disorders. The mean age was 77.6+/-7.9. Number of women: 63
      (92.6%). Previous Barthel Index was 94/100, cognitive impairment 23 (33.8%),
      polypharmacy 69.1%, orthostatic hypotension 18 (26.4%). Walking speed 0.66+/-
      0.19m/s and Time up and go to (TUG) 16.6+/-4.5 s. Post-urography detected
      vestibular dysfunction in 34 patients (77%). Clinical cause of fall and/or gait
      disorder was multifactorial in 33 (48.5%), Parkinsonism 19 (27.9%), chronic
      pain/arthropathy 8 (11.4%), and vestibular syndrome 8 (11.4%). Two-thirds (45;
      66.1%) of the patients began Physical therapy, and vitamin D was given to 47
      (69.1%). Phone calls were made to patients and/or their relatives and noted that
      after 3 months of the treatment: 48 (70.5%) had no fall; 59 (86.7%) patients
      followed the recommendations, and 57 (83.8%) were satisfied. CONCLUSIONS: In this
      sample of older patients, mostly female with a good functional and cognitive
      condition, the causes of the falls were multifactorial in the half of the cases,
      and the post-urography detected vestibular changes in the half of the patients.

PMID- 24280015
TI  - Loss aversion and 5HTT gene variants in adolescent anxiety.
AB  - Loss aversion, a well-documented behavioral phenomenon, characterizes decisions
      under risk in adult populations. As such, loss aversion may provide a reliable
      measure of risky behavior. Surprisingly, little is known about loss aversion in
      adolescents, a group who manifests risk-taking behavior, or in anxiety disorders,
      which are associated with risk-avoidance. Finally, loss aversion is expected to
      be modulated by genotype, particularly the serotonin transporter (SERT) gene
      variant, based on its role in anxiety and impulsivity. This genetic modulation
      may also differ between anxious and healthy adolescents, given their distinct
      propensities for risk taking. The present work examines the modulation of loss
      aversion, an index of risk-taking, and reaction-time to decision, an index of
      impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in
      healthy and clinically anxious adolescents. Findings show that loss aversion (1)
      does manifest in adolescents, (2) does not differ between healthy and clinically
      anxious participants, and (3), when stratified by SERT genotype, identifies a
      subset of anxious adolescents who are high SERT-expressers, and show excessively
      low loss-aversion and high impulsivity. This last finding may serve as
      preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid
      disorders associated with risk-taking and impulsivity in clinically anxious
      adolescents. 

PMID- 24280016
TI  - Oxytocin in learning and addiction: From early discoveries to the present.
AB  - Oxytocin (OXT) has a plethora of effects on brain function. This review provides
      a historical overview of the development of research on OXT and drug addiction.
      By focusing on research that has emerged from our laboratories, we describe how
      early discoveries of the influence of OXT on learning and memory processes and
      the emerging conceptualization of addiction as 'pathological learning' have
      contributed to the demonstration that OXT effectively attenuates long-term
      neuroadaptation related to opiate and psychostimulant addiction. Through
      integrating earlier evidence with recent discoveries of the social/affiliative
      role of OXT, we propose that OXT may interfere with reward and addiction by
      influencing neurobiological processes involved in stress, learning and memory and
      social/affiliative behavior. 

PMID- 24280017
TI  - Applications of NMR screening techniques to the pharmaceutical target Checkpoint
      kinase 1.
AB  - Ligand screening techniques based on NMR spectroscopy are not as sensitive as
      other commonly used methods like fluorescence, radiolabeling and surface plasmon
      resonance. However, using modern NMR instrumentation, they can achieve reliable
      screening under near physiological condition using as little as 4.6 nmol of
      receptor and 100 nmol of ligand. Additionally, these NMR methods can also provide
      valuable and specific information on the ligand under investigation such as the
      dissociation constant KD, the binding epitope and most importantly some
      structural information on the actual conformation in the bound state. In this
      manuscript, we describe the use of NMR based screening techniques ("Saturation
      Transfer Difference" (STD) and "Water Ligand Observed via Gradient SpectroscopY"
      (WaterLOGSY)) to detect small therapeutic molecules that interact with the DNA
      damage checkpoint enzyme Checkpoint kinase 1 (Chk1). After the identification of
      the most potent ligand, we used specific NMR experiments to perform the epitope
      mapping of this ligand ("Group epitope mapping-STD" (GEM-STD), "Difference of
      Inversion REcovery rate with and without Target IrradiatiON" (DIRECTION)) and to
      characterize its bound conformation ("Transferred-Nuclear Overhauser Effect
      SpectroscopY" (tr-NOESY), "Transferred-Rotating frame Overhauser Effect
      SpectroscopY" (tr-ROESY)). Finally, we used molecular docking procedures to
      position the ligand within the active site of Chk1. On the experimental level, a
      comparison between NMR studies performed in a 90%H2O/10%D2O buffer and a 100% D2O
      buffer is also presented and discussed.

PMID- 24280018
TI  - Desktop 3D printing of controlled release pharmaceutical bilayer tablets.
AB  - Three dimensional (3D) printing was used as a novel medicine formulation
      technique for production of viable tablets capable of satisfying regulatory tests
      and matching the release of standard commercial tablets. Hydroxypropyl
      methylcellulose (HPMC 2208) (MethocelTM K100M Premium) and poly(acrylic acid)
      (PAA) (Carbopol((r)) 974P NF) were used as a hydrophilic matrix for a sustained
      release (SR) layer. Hypromellose((r)) (HPMC 2910) was used as a binder while
      microcrystalline cellulose (MCC) (Pharmacel((r)) 102) and sodium starch glycolate
      (SSG) (Primojel((r))) were used as disintegrants for an immediate release (IR)
      layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug
      (Mucinex((r))) for this study. There was a favourable comparison of release of
      the active guaifenesin from the printed hydrophilic matrix compared with the
      commercially available GBT. The printed formulations were also evaluated for
      physical and mechanical properties such as weight variation, friability, hardness
      and thickness as a comparison to the commercial tablet and were within acceptable
      range as defined by the international standards stated in the United States
      Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets)
      showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian
      diffusion drug release through a hydrated HPMC gel layer.

PMID- 24280019
TI  - Crystal suspensions of poorly soluble peptides for intra-articular application: a
      novel approach for biorelevant assessment of their in vitro release.
AB  - Crystal suspensions of 3 poorly soluble peptides (MSC1, 2 and 3), intended for
      intra-articular administration were prepared and in vitro release was tested by a
      modified USP IV apparatus, combined with a dialysis system. Half-lives of release
      profiles were ~5 days for MSC1 and ~0.5 days for MSC2 and MSC3, showing the
      potential to achieve sustained exposure from crystal suspensions after intra
      articular administration. The in vitro release setup discriminated between (i)
      different formulations, (ii) different concentrations of API and (iii) different
      APIs. In addition it was shown that this method allows the modification of
      release conditions in order to gain more biorelevance for in vitro release
      testing in the field of intra-articular application: the influence of synovial
      fluid components hyaluronic acid and albumin was demonstrated, showing prolonged
      half-lives for suspensions containing 2.5% bovine serum albumin (5 days) and
      accelerated release rates for suspensions containing 1% sodium hyaluronate (2.5
      days) in comparison to a suspension in phosphate buffered saline (4 days).
      Furthermore, it was demonstrated that release rates of a suspension containing an
      artificial synovial fluid were in accordance with suspensions containing bovine
      synovial fluid (t1/2~4 days). 

PMID- 24280021
TI  - Clinical correlates of serum insulin-like growth factor-1 in patients with
      Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.
AB  - BACKGROUND: Recently, increased serum insulin-like growth factor-1 (IGF-1) levels
      have been reported in patients with Parkinson's disease (PD) and multiple system
      atrophy (MSA). OBJECTIVE: To assess a correlation between the serum IGF-1 levels
      and clinical background factors in patients with PD and related disorders such as
      MSA and progressive supranuclear palsy (PSP). METHODS: A total of 79 PD patients,
      25 MSA patients, 16 PSP patients and 52 healthy controls were included in this
      study. The serum IGF-1 and growth hormone (GH) levels were measured in a fasting
      state. Unified PD Rating Scale (UPDRS) part III was used to evaluate motor
      function. Unified MSA Rating Scale (UMSARS) part II was also employed for the MSA
      patients. RESULTS: The serum IGF-1 levels were significantly increased in the MSA
      patients compared with the PD patients and controls. No significant differences
      were observed in the serum GH levels among the patients and controls. The serum
      IGF-1 levels of PD patients with Hoehn and Yahr stage 2 were significantly higher
      than those of patients with Hoehn and Yahr stages 3-5. In patients with PD and
      PSP, the serum IGF-1 levels were negatively correlated with UPDRS part III. In
      contrast, patients with MSA showed a positive correlation of the serum IGF-1
      levels with disease duration, UPDRS part III and UMSARS part II. CONCLUSION: The
      difference in the serum IGF-1 level and its correlation with clinical variables
      among these disorders may reflect different ongoing disease processes in each
      disorder.

PMID- 24280020
TI  - Meta-analysis and The Cochrane Collaboration: 20 years of the Cochrane
      Statistical Methods Group.
AB  - The Statistical Methods Group has played a pivotal role in The Cochrane
      Collaboration over the past 20 years. The Statistical Methods Group has
      determined the direction of statistical methods used within Cochrane reviews,
      developed guidance for these methods, provided training, and continued to discuss
      and consider new and controversial issues in meta-analysis. The contribution of
      Statistical Methods Group members to the meta-analysis literature has been
      extensive and has helped to shape the wider meta-analysis landscape.In this
      paper, marking the 20th anniversary of The Cochrane Collaboration, we reflect on
      the history of the Statistical Methods Group, beginning in 1993 with the
      identification of aspects of statistical synthesis for which consensus was
      lacking about the best approach. We highlight some landmark methodological
      developments that Statistical Methods Group members have contributed to in the
      field of meta-analysis. We discuss how the Group implements and disseminates
      statistical methods within The Cochrane Collaboration. Finally, we consider the
      importance of robust statistical methodology for Cochrane systematic reviews,
      note research gaps, and reflect on the challenges that the Statistical Methods
      Group faces in its future direction.

PMID- 24280022
TI  - Triggering essential head tremor with sustained phonation: a clinical phenomenon
      with potential diagnostic value.
AB  - Here we report a clinical phenomenon that we have observed repeatedly in clinical
      research settings; namely, a triggering and/or exacerbation of head tremor during
      or immediately following sustained phonation. To our knowledge, it has not been
      reported previously nor has it been the subject of study. Here we: 1) report the
      phenomenon, 2) provide several visual illustrations, 3) estimate its prevalence,
      and 4) analyze its clinical correlates. Head tremor was assessed qualitatively,
      and scores were assigned pre-, during, and post-sustained phonation using the
      Tremor Research Group Essential Tremor Rating Assessment Scale. Seventy (68.6%)
      of 102 essential tremor (ET) patients exhibited a qualitative increase in head
      tremor amplitude during and/or immediately after sustained phonation; in 5
      (4.9%), head tremor would not have been detected without the voice activation
      maneuver (i.e., it was not visible at any other point in the videotape aside from
      the period during/immediately following sustained phonation). Women were more
      likely than men to exhibit this phenomenon (p = 0.05), whereas age, age at onset,
      duration of tremor, and total tremor score did not predict responsiveness of head
      tremor to sustained phonation. Sustained voice activation is a useful examination
      maneuver that may elicit or amplify head tremor in ET. Head tremor is not
      reported to occur in patients with enhanced physiological tremor. Thus, this
      maneuver, by triggering head tremor, may be a useful diagnostic supplement,
      particularly in research/clinical settings where arm tremor is mild and the
      diagnosis (mild ET vs. enhanced physiological tremor) would otherwise be
      ambiguous.

PMID- 24280024
TI  - Palliative and end of life care for people with dementia: lessons for clinical
      commissioners.
AB  - AIM: To synthesize information about management of end of life care in people
      with dementia using review papers. BACKGROUND: There are increasing numbers of
      people being diagnosed with dementia worldwide, and the needs of people with
      dementia and their carers at the end of life may be different from those with
      other chronic diseases. By highlighting the challenges of palliative care in
      persons with dementia and the ways they are best managed, practitioners in
      primary care may be able to improve services for this group of people at the end
      of life. METHODS: A search of electronic databases of English language papers
      published in peer-reviewed journals, 2000-2011 inclusive was undertaken using
      broad terms related to palliative care and dementia. 6167 papers were identified.
      Titles and abstracts were read. Papers were included if they were literature
      reviews of palliative or end of life care for people with dementia/Parkinson's
      disease/Lewy body dementia/cognitive impairment/Alzheimer's disease or any other
      cognitive impairment, in any setting (hospital, care home, community) and
      covering people of all ages. Papers were excluded if they covered palliative care
      focusing on other conditions, or were about an aspect of dementia care and
      treatment not related to palliative care. FINDINGS: Our critical synthesis
      generated five main themes from this review of the reviews: (1) carers' (family
      caregivers') experiences; (2) person-centred care; (3) practice (including
      advance care planning, pain and comfort, nutrition, medical complications and
      minimizing the distress of behavioural symptoms); (4) system factors, including
      ethical dilemmas, decision making, information, and training; and (5) research
      priorities. There appears to be good evidence on the care and management of
      patients with dementia at the end of life which can be used to influence policy
      development and emerging specificity about research priorities in palliative care
      practice for people with dementia.

PMID- 24280023
TI  - Recognizing the enemy within: licensing RNA-guided genome defense.
AB  - How do cells distinguish normal genes from transposons? Although much has been
      learned about RNAi-related RNA silencing pathways responsible for genome defense,
      this fundamental question remains. The literature points to several classes of
      mechanisms. In some cases, double-stranded RNA (dsRNA) structures produced by
      transposon inverted repeats or antisense integration trigger endogenous small
      interfering RNA (siRNA) biogenesis. In other instances, DNA features associated
      with transposons--such as their unusual copy number, chromosomal arrangement,
      and/or chromatin environment--license RNA silencing. Finally, recent studies have
      identified improper transcript processing events, such as stalled pre-mRNA
      splicing, as signals for siRNA production. Thus, the suboptimal gene expression
      properties of selfish elements can enable their identification by RNA silencing
      pathways.

PMID- 24280025
TI  - Heritable alteration in salt-tolerance in rice induced by introgression from wild
      rice (Zizania latifolia).
AB  - BACKGROUND: Introgression as a means of generating phenotypic novelty, including
      altered stress tolerance, is increasingly being recognized as common. The
      underlying basis for de novo genesis of phenotypic variation in the introgression
      lines remains largely unexplored. In this investigation, we used a rice line
      (RZ35) derived from introgressive hybridization between rice (Oryza sativa L.)
      and wild rice (Zizania latifolia Griseb.), along with its rice parental line (cv.
      Matsumae) as the experimental materials. We compared effects of salt stress on
      growth, ion homeostasis, and relevant gene expression between RZ35 and Matsumae,
      to explore possible mechanisms of heritable alteration in stress tolerance
      induced by the introgression. RESULTS: Contrary to our expectation, the results
      showed that the inhibitory effect of salt stress on growth of RZ35 was
      significantly greater than that of Matsumae. We further found that a major
      underlying cause for this outcome is that the introgression process weakened the
      capacity in Na+ exclusion under the salt stress condition, and hence, escalated
      the injuries of Na+ and Cl- in shoots of RZ35. Accordingly, based on q-RT-PCR
      analysis, four genes known to be involved in the Na+ exclusion, i.e., OsHKT1;5,
      OsSOS1, OsCIPK24 and OsCBL4, were found to be significantly down-regulated in
      roots of RZ35 relative to its rice parental line under the salt stress condition,
      thus implicating a gene expression regulation-based molecular mechanism
      underlying the difference in salt stress-tolerance between the introgression line
      and its rice parental line. CONCLUSIONS: We show that introgression represents a
      potent means for rapidly generating de novo heritable variations in physiological
      traits like stress tolerance in plants, although the direction of the alteration
      appears unpredictable.

PMID- 24280026
TI  - Monitoring metabolic responses to chemotherapy in single cells and tumors using
      nanostructure-initiator mass spectrometry (NIMS) imaging.
AB  - BACKGROUND: Tissue imaging of treatment-induced metabolic changes is useful for
      optimizing cancer therapies, but commonly used methods require trade-offs between
      assay sensitivity and spatial resolution. Nanostructure-Initiator Mass
      Spectrometry imaging (NIMS) permits quantitative co-localization of drugs and
      treatment response biomarkers in cells and tissues with relatively high
      resolution. The present feasibility studies use NIMS to monitor phosphorylation
      of 3'-deoxy-3'-fluorothymidine (FLT) to FLT-MP in lymphoma cells and solid tumors
      as an indicator of drug exposure and pharmacodynamic responses. METHODS: NIMS
      analytical sensitivity and spatial resolution were examined in cultured Burkitt's
      lymphoma cells treated briefly with Rapamycin or FLT. Sample aliquots were
      dispersed on NIMS surfaces for single cell imaging and metabolic profiling, or
      extracted in parallel for LC-MS/MS analysis. Docetaxel-induced changes in FLT
      metabolism were also monitored in tissues and tissue extracts from mice bearing
      drug-sensitive tumor xenografts. To correct for variations in FLT disposition,
      the ratio of FLT-MP to FLT was used as a measure of TK1 thymidine kinase activity
      in NIMS images. TK1 and tumor-specific luciferase were measured in adjacent
      tissue sections using immuno-fluorescence microscopy. RESULTS: NIMS and LC-MS/MS
      yielded consistent results. FLT, FLT-MP, and Rapamycin were readily detected at
      the single cell level using NIMS. Rapid changes in endogenous metabolism were
      detected in drug-treated cells, and rapid accumulation of FLT-MP was seen in
      most, but not all imaged cells. FLT-MP accumulation in xenograft tumors was shown
      to be sensitive to Docetaxel treatment, and TK1 immunoreactivity co-localized
      with tumor-specific antigens in xenograft tumors, supporting a role for xenograft
      derived TK1 activity in tumor FLT metabolism. CONCLUSIONS: NIMS is suitable for
      monitoring drug exposure and metabolite biotransformation with essentially single
      cell resolution, and provides new spatial and functional dimensions to studies of
      cancer metabolism without the need for radiotracers or tissue extraction. These
      findings should prove useful for in vitro and pre-clinical studies of cancer
      metabolism, and aid the optimization of metabolism-based cancer therapies and
      diagnostics.

PMID- 24280027
TI  - A point mutation in the zinc finger motif of RID1/EHD2/OsID1 protein leads to
      outstanding yield-related traits in japonica rice variety Wuyunjing 7.
AB  - BACKGROUND: Flowering time, which is often associated with the length of the
      growth period in rice, determines the adaptability of a plant to various
      environments. However, little is known about how flowering-time genes affect
      panicle development and yield formation potential in rice after inducing the
      transition from vegetative growth to reproductive growth. RESULTS: To explore the
      relationship between floral induction and yield formation and the molecular
      mechanism of panicle development in rice, a novel mutant, ghd10, was identified
      from japonica variety Wuyunjing 7 plants subjected to ethyl methane sulfonate
      (EMS) treatment. The ghd10 mutant exhibited delayed flowering time, tall stalks
      and increased panicle length and primary branch number. Map-based cloning
      revealed that Ghd10 encodes a transcription factor with Cys-2/His-2-type zinc
      finger motifs. Ghd10 is orthologous to INDETERMINATE1 (ID1), which promotes
      flowering in maize (Zea mays) and is identical to the previously cloned genes
      Rice Indeterminate1 (RID1), Early heading date2 (Ehd2) and OsId1. Transient
      expression analysis of the Ghd10-GFP fusion protein in tobacco mesophyll cells
      showed that this protein is expressed in the nucleus. Ghd10 mRNA accumulated most
      abundantly in developing leaves and panicle structures, but rarely in roots.
      Expression analysis revealed that the expression levels of Ehd1, Hd1, RFT1, Hd3a
      and OsMADS15 decreased dramatically under both short-day and long-day conditions
      in ghd10. CONCLUSION: These results indicate that Ghd10, which encodes a promoter
      of flowering, influences plant height and panicle development by regulating the
      expression levels of some flowering-related genes, such as Ehd1, Hd1, OsMADS15
      and others. The ghd10 allele is a useful resource for improvement of panicle
      traits in rice grown in tropical and low-latitude areas.

PMID- 24280028
TI  - Molecular identification of hookworms in stray and shelter dogs from Guangzhou
      city, China using ITS sequences.
AB  - Canine hookworm infections are endemic worldwide, with zoonotic transmission
      representing a potentially significant public health concern. This study aimed to
      investigate hookworm infection and identify the prevalent species from stray and
      shelter dogs in Guangzhou city, southern China by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) based on internal transcribed
      spacer (ITS) sequences. From March 2011 to July 2012, fresh faecal samples from a
      total of 254 dogs were obtained from five locations, namely Conghua, Baiyun,
      Liwan, Haizhu and Panyu, in Guangzhou. These samples were screened for the
      presence of hookworm eggs using light microscopy, with an overall prevalence of
      29.53% being recorded. The highest prevalence of 45.28% was found in suburban
      dogs from Conghua compared with lower values recorded in urban dogs in Haizhu
      (21.43%), Baiyun (18.97%), Panyu (18.18%) and Liwan (15%). The prevalence in
      stray dogs was significantly higher than that in shelter dogs. PCR-RFLP analysis
      showed that 57.33% were detected as single hookworm infections with Ancyclostoma
      caninum, and 22.67% as A. ceylanicum, while 20% were mixed infections. This
      suggests that high prevalences of both hookworm species in stray and shelter dogs
      in China pose a potential risk of transmission from pet dogs to humans. 

PMID- 24280029
TI  - A Chinese medicine preparation induces neuroprotection by regulating paracrine
      signaling of brain microvascular endothelial cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tong Luo Jiu Nao injection (TLJN), a Chinese
      medicine preparation, was extracted from the Chinese herbs Panax notoginseng and
      Gardenia jasminoides. Its pharmacological effect on cerebral ischemia was
      observed in the study. We previously reported that paracrine signaling of brain
      microvascular endothelial cells (BMECs) had a direct impact on the survival of
      neurons in mimicked cerebral ischemia in vitro. The current study was designed to
      investigate whether paracrine signaling of BMECs could be regulated by drug to
      achieve neuroprotection. MATERIALS AND METHODS: First, an in vitro model of
      cerebral ischemia in BMECs or neurons was established by oxygen-glucose
      deprivation (OGD). TLJN was used as a medicine of intervention. Injured neurons
      were cultured in the conditioned media from normal and injured BMECs treated with
      TLJN. The changes in neurons, including the expression of N-methyl-D-aspartate
      receptor 1(NMDAR1), Ca(2+) concentration, cytochrome c release, the mitochondrial
      membrane potential, were determined by the immunofluorescence staining and
      molecular Probes. The content of Vascular endothelial growth factor (VEGF) and
      platelet activating factor (PAF) in various BMECs were also examined by Western
      blotting and Elisa. RESULTS: The results showed the activity of injured neurons
      was significantly increased when they were grown in conditioned media of normal
      or injured BMECs treated with TLJN, compared with that of normal or injured
      BMECs. These changes include a decrease of Ca(2+) concentration, of NMDAR1
      expression, and of cytochrome c release, also an increase of the mitochondrial
      membrane potential. Moreover, the VEGF expression was up-regulated and the PAF
      expression was down-regulated by TLJN in BMECs. CONCLUSION: The results suggest
      that a neuroprotective effect of TLJN could be achieved by regulating paracrine
      signaling of BMECs, which could in part be explained by a TLJN-induced up
      regulation of VEGF and a down-regulation of PAF in BMECs. Therefore, regulating
      the paracrine of BMECs could be the important target of the drug action on
      injured-neurons, which may be a novel path for therapeutic intervention in
      ischemic injury.

PMID- 24280030
TI  - Studies on neutralizing effect of Ophiorrhiza mungos root extract against Daboia
      russelii venom.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The folklore or traditional therapy in southern
      India widely utilizes a plethora of local herbs to treat the patients challenged
      with snake venom. Despite the widespread implementation of antisera therapy, the
      local population of the country still relies on this century's old medicinal
      formulas mainly due to the cost effectiveness, lesser side effects and also its
      cultural acceptability. The present study aims to validate the neutralizing
      ability of one such traditionally acclaimed antidote Ophiorrhiza mungos root
      extract against Russell's viper (Daboia russelii) venom in the early developing
      chick embryos. MATERIALS AND METHODS: The disc impregnated with venom, root
      extract or the combination of both was placed on the yolk sac membrane preferably
      over the anterior blood vessel of 6th day chick embryo. The
      neutralization/inhibition of venom-induced lethality or hemorrhage was achieved
      by incubating venom and extract before being applied to the embryo. The membrane
      stabilizing properties of root extract was estimated by HRBC lysis method. The
      preliminary phytochemical analysis was done to assess the phyto constituents in
      the root extract. RESULTS: The LD50 of Russell's viper venom in 6th day chick
      embryo was found to be 3 MUg/MUl. The neutralising effect of root extract was
      achieved by pre-incubating venom with various concentrations of extract and at
      the concentration of 10 MUg/MUl, 100% recovery of embryos was observed after 6h
      of incubation. Higher concentration of root extract showed remarkable results by
      completely abolishing traces of hemorrhagic lesions induced by viper venom.
      CONCLUSIONS: The above observations confirmed that the root extract of
      Ophiorrhiza mungos possess potent anti snake venom neutralizing compounds, which
      inhibit the activity of viper venom. The chick embryo, a new insensate model used
      in the present study is significant in venom research as it reduces the ruthless
      suffering of higher mammalian experimental models.

PMID- 24280032
TI  - Biophysical characterization of in vitro bound Streptomyces peucetius
      daunorubicin-serine protease complex.
AB  - A serine protease of Streptomyces peucetius is found in association with
      daunorubicin in the culture filtrate and co-purifies as a complex as reported
      earlier by us (Dubey et al., 2013). The same protease was purified without drug
      attachment from dpsA(-) mutant of S. peucetius, which does not produce
      daunorubicin. Drug-protein complex was made in vitro by mixing daunorubicin and
      the protease. Spectral analysis and circular dichroism (CD) analysis were
      employed to determine the interaction between daunorubicin and the protease. Our
      study showed that interaction of daunorubicin with the protease affects the
      spectral characteristics of the drug and changes the secondary structure of the
      protein. Thin layer chromatography (TLC) analysis showed that the drug-protein
      interaction results in partial conversion of the drug to aglyconic form. The
      complex formation implies sequestration of the drug when it attains potentially
      lethal level in the extracellular milieu of S. peucetius culture. 

PMID- 24280031
TI  - A double-blind, randomized trial of deep repetitive transcranial magnetic
      stimulation (rTMS) for autism spectrum disorder.
AB  - BACKGROUND: Biomedical treatment options for autism spectrum disorder (ASD) are
      extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe
      and efficacious technique when targeting specific areas of cortical dysfunction
      in major depressive disorder, and a similar approach could yield therapeutic
      benefits in ASD, if applied to relevant cortical regions. OBJECTIVE: The aim of
      this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal
      cortex improves social relating in ASD. METHODS: 28 adults diagnosed with either
      autistic disorder (high-functioning) or Asperger's disorder completed a
      prospective, double-blind, randomized, placebo-controlled design with 2 weeks of
      daily weekday treatment. This involved deep rTMS to bilateral dorsomedial
      prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15
      min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased
      in the same helmet of the active deep rTMS coil, but no effective field was
      delivered into the brain. Assessments were conducted before, after, and one month
      following treatment. RESULTS: Participants in the active condition showed a near
      significant reduction in self-reported social relating symptoms from pre
      treatment to one month follow-up, and a significant reduction in social relating
      symptoms (relative to sham participants) for both post-treatment assessments.
      Those in the active condition also showed a reduction in self-oriented anxiety
      during difficult and emotional social situations from pre-treatment to one month
      follow-up. There were no changes for those in the sham condition. CONCLUSION:
      Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in
      social relating impairment and socially-related anxiety. Further research in this
      area should employ extended rTMS protocols that approximate those used in
      depression in an attempt to replicate and amplify the clinical response.

PMID- 24280033
TI  - Complexity of the tear film: importance in homeostasis and dysfunction during
      disease.

PMID- 24280035
TI  - [How to design workshops to promote health in community groups].
AB  - One of the strategies of health promotion is to develop life skills people
      considering themselves as the main health resource. A workshop has to get its
      participants become "asset" to make decisions and create health, focusing on the
      development and acquisition of skills in a motivating group and in order to
      achieve health objectives. The concepts behind the design of a workshop are:
      participatory planning, training, meaningful learning, group learning and
      participatory techniques. The steps to follow to design a workshop and facilitate
      their application are: Stage 0, founding; initial stage, host and initial
      evaluation; central or construction stage based learning in the acquisition of
      knowledge, attitudes and skills, and final stage or evaluation.

PMID- 24280034
TI  - Haemoglobin concentration and mass as determinants of exercise performance and of
      surgical outcome.
AB  - The ability of the cardiorespiratory system (heart, lungs, blood) to deliver
      oxygen to exercising skeletal muscle constrains maximum oxygen consumption
      VO2max, with cardiac output and the concentration of oxygen-carrying haemoglobin
      ([Hb]) being key limiting parameters. Total blood volume (BV) is the sum of the
      plasma volume (PV) and the total red cell volume. The measured [Hb] is dependent
      upon the total circulating mass of haemoglobin (tHb-mass) and plasma volume (PV).
      While the proportion of oxygen carried in plasma is trivial (0.3 mL of oxygen per
      100 mL of plasma), each gram of Hb, contained in red blood cells, binds 1.39 mL
      of oxygen. As a result, the relationship between VO2max and tHb-mass is stronger
      than that observed between VO2max and [Hb] or BV. The glycoprotein hormone
      erythropoietin drives red cell synthesis and, like simple transfusion of packed
      red blood cells, can increase tHb-mass. An iron-containing haem group lies at the
      centre of the Hb molecule and, in situations of actual or functional iron
      deficiency, tHb-mass will also rise following iron administration. However
      achieved, an increase in tHb-mass also increases circulating oxygen-carrying
      capacity, and thus the capacity for aerobic phosphorylation. It is for such
      reasons that alterations in VO2max and exercise performance are proportional to
      those in arterial oxygen content and systemic oxygen transport, a change in tHb
      mass of 1 g being associated with a 4 mL . min-1 change in VO2max. Similarly,
      VO2max increases by approximately 1% for each 3 g . L-1 increase in [Hb] over the
      [Hb] range (120 to 170 g . L-1). Surgery, like exercise, places substantial
      metabolic demands on the patient. Whilst subject to debate, oxygen supply at a
      rate inadequate to prevent muscle anaerobiosis may underpin the occurrence of the
      anaerobic threshold (AT), an important submaximal marker of cardiorespiratory
      fitness. Preoperatively, cardiopulmonary exercise testing (CPET) can be used to
      determine AT and peak exertional oxygen uptake (VO2 peak) as measures of ability
      to meet increasing oxygen demands. The degree of surgical insult and the ability
      to meet the resulting additional postoperative oxygen demand appear to be
      fundamental determinants of surgical outcome: individuals in whom such ability is
      impaired (and thus those with reduced VO2 peak and AT) are at greater risk of
      adverse surgical outcome. This review provides an overview of the relationships
      between [Hb], tHb-mass, exercise capacity, and surgical outcome and discusses the
      potential value of assessing tHb-mass over [Hb]. 

PMID- 24280036
TI  - [Research within the reach of Osakidetza professionals: Primary Health Care
      Research Program].
AB  - OBJECTIVE: To provide information about the process and results of the Primary
      Health Care Research Program 2010-2011 organised by the Primary Care Research
      Unit of Bizkaia. DESIGN: Descriptive study. SETTING: Osakidetza primary care.
      PARTICIPANTS: The 107 health professionals who applied for the program from a
      total of 4,338 general practitioners, nurses and administrative staff who were
      informed about it. MAIN MEASURES: Application level, research topics
      classification, program evaluation by participants, projects funding and program
      costs. RESULTS: Percentage who applied, 2.47%; 95% CI 2.41-2.88%. Of the 28 who
      were selected and 19 completed. The research topics were mostly related to the
      more common chronic diseases (32%), and prevention and health promotion (18%).
      Over 90% of participants assessed the quality of the program as good or
      excellent, and half of them considered it as difficult or very difficult. Of
      the18 new projects generated, 12 received funding, with 16 grants, 10 from the
      Health Department of the Basque Government, 4 from the Carlos III Institute of
      Health of the Ministry of Health of Spain, and 2 from Kronikgune. A total of
      ?500,000 was obtained for these projects. This program cost ?198,327.
      CONCLUSIONS: This experience can be used by others interested in the promotion of
      research in primary care, as the program achieved its objectives, and was useful
      and productive.

PMID- 24280037
TI  - Communication self-efficacy, perceived conversational difficulty, and renal
      patients' discussions about transplantation.
AB  - OBJECTIVE: Many patients with chronic and end-stage renal disease (ESRD) have
      reported difficulties initiating and managing discussions about kidney
      transplantation, particularly live donor transplantation (LDT). Limited
      communication has demonstrable impact on patients' access to transplantation, the
      duration of dialysis treatments, and the length of time awaiting a transplantable
      kidney. This formative study sought to identify the specific communicative and
      conversational elements impeding ESRD patients' discussions about transplantation
      to inform the design of an educational program facilitating transplant-related
      discussions. METHODS: From March to July 2012, semi-structured telephone
      interviews (n=63) were conducted with ESRD patients waitlisted for kidney
      transplantation at one mid-Atlantic transplant center. RESULTS: Although 85.7%
      (n=54) of patients reported holding discussions about transplantation,
      qualitative analyses of open-ended responses revealed that the majority (66.7%)
      had limited conversations. Patients reported difficulties managing a variety of
      logistical and content-related aspects of LDT discussions. Moderate levels of
      communication self-efficacy were also found (mean=19.2 out of 28); self-efficacy
      was highest among respondents having held discussions and was significantly
      related to perceived magnitude of difficulty handling conversational aspects.
      CONCLUSION: Results support comprehensive communication skills training for ESRD
      patients awaiting kidney transplantation. PRACTICE IMPLICATIONS: Potential topics
      to be included in such training are discussed.

PMID- 24280038
TI  - Hydration status in elite wrestlers, judokas, boxers, and taekwondo athletes on
      competition day.
AB  - Weight category athletes are known for practicing rapid weight loss before
      competition weigh-in. After weigh-in, athletes strive to restore euhydration and
      body mass through food and fluid intake. The aim of the current study was to
      assess prevalence of hypohydration at competition time among elite athletes' in
      four different combat sports, and how water intake and timing of official weigh
      in were related to hydration status. Participants were 31 taekwondo practitioners
      and wrestlers who performed evening weigh-in (EWI) the night before competition
      day and had thus time for rehydration, and 32 boxers and judokas conducting
      competition day morning weigh-in (MWI). In total, 32% were female. Urine specific
      gravity (USG) was measured by refractometry on the competition day's first
      morning urine sample. Hypohydration was defined as USG >= 1.020 and serious
      hypohydration as USG > 1.030. Water intake was measured by means of dietary
      records. The prevalence of hypohydration was 89% in the morning of competition
      day. Serious hypohydration was also prevalent. This was found in over 50% of MWI
      athletes and in 42% of the EWI group. A higher water intake, from both fluids and
      solid foods, in the evening before competition day was not associated with a more
      favorable hydration status the following morning. In conclusion, neither weigh-in
      close to competition nor evening weigh-in with more time for rehydration seems to
      prevent hypohydration before competition.

PMID- 24280039
TI  - Diagnostic test accuracy of clinical and radiological assessments for medial
      patella plica syndrome: a systematic review and meta-analysis.
AB  - BACKGROUND: The diagnosis of medial patella plica (MPP) syndrome is challenging
      due to poor clinical knowledge and controversies surrounding clinical and
      radiological diagnosis. The purpose of this study is to determine the diagnostic
      accuracy of clinical tests and radiological imaging in the detection of MPP
      syndrome. METHODS: A systematic review of the electronic databases EMBASE,
      MEDLINE, Science Direct and Scopus was undertaken. All studies which compared the
      accuracy of a clinical test, magnetic resonance imaging (MRI) or ultrasound (USS)
      (index tests) to assess the presence of MPP syndrome, against a surgical
      procedure (reference test) were included. Methodological appraisal using the
      QUADAS tool was conducted. The data was analyzed with pooled sensitivity and
      specificity meta-analyses with 95% confidence intervals. RESULTS: Seven studies
      including 492 knees were reviewed. The MPP (physical examination) test
      (sensitivity=0.90; specificity=0.89) and USS (sensitivity=0.90; specificity=0.83)
      demonstrated the greatest diagnostic test accuracy. MRI demonstrated a
      sensitivity of 0.77 and specificity of 0.58. The literature presented with
      moderate methodological quality. CONCLUSIONS: The MPP test and USS are valuable
      in the diagnosis of MPP syndrome. The reference standard for future research in
      this area should be the resolution of symptoms following MPP resection, instead
      of arthroscopic evaluation. LEVEL OF EVIDENCE: 3a.

PMID- 24280040
TI  - Methods for assessing phosphorus overfeeding on organic and conventional dairy
      farms.
AB  - Phosphorus (P) losses from dairy farms can severely damage aquatic ecosystems, so
      it is important to have tools to assess overfeeding of P. This study screened P
      intake and faecal excretion of different P fractions in dairy cows on
      conventional and organic farms, compared the P feeding level of the herds against
      the recommendations and analysed different sampling and analysis methods for
      assessing the general status of P feeding on the farms. The organic (n=14) and
      conventional farms (n=15) were of comparable size and were located in southern
      Sweden. On each farm, feed intake was registered for 10 cows representing four
      different lactation stages and their P intake was calculated and related to
      current recommendations. Faecal samples taken from the same cows were analysed
      for total P (TP) and soluble P. Milk production data for the cows were obtained
      from the Swedish official milk recording scheme. TP was determined in one slurry
      sample per farm. More than 70% of the cows studied, representing both
      conventional and organic herds, consumed P in excess of the recommendations.
      Conventional herds had higher P content in the ration than organic herds, and
      lactating cows in conventional herds had higher faecal concentrations of total
      and soluble P than those in organic herds. However in dry cows, the P content of
      the ration and soluble P and TP in faeces did not differ between the two
      management systems. Soluble P was well correlated to TP in faeces, and both were
      good indicators of P overfeeding. 

PMID- 24280041
TI  - Aerobic exercise training decreases plasma asymmetric dimethylarginine
      concentrations with increase in arterial compliance in postmenopausal women.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric
      oxide synthase, increase with advancing age and menopausal status. ADMA plays a
      role in endothelial dysfunction and increasing arterial stiffness. Regular
      aerobic exercise has a positive effect on arterial function (i.e., arterial
      compliance). This study investigated the effects of aerobic exercise training on
      plasma ADMA concentrations and arterial compliance in postmenopausal women.
      METHODS: Thirty postmenopausal women were divided into 2 groups: an exercise
      group (n = 20) and a control group (n = 10). Subjects in the exercise group
      completed 12 weeks of aerobic exercise training (65%-80% of maximal heart rate,
      40-60 min/day, 3-6 days/week). Before and after each intervention, plasma ADMA
      concentrations and carotid arterial compliance were measured in all participants.
      RESULTS: The baseline plasma ADMA concentrations, carotid arterial compliance,
      and most other key dependent variables did not differ between the 2 groups. In
      the exercise group, carotid arterial compliance significantly increased after
      exercise intervention (P < 0.01), and plasma ADMA concentrations significantly
      decreased (P < 0.05). In addition, changes in carotid arterial compliance after
      the exercise intervention were inversely correlated with changes in plasma ADMA
      concentrations (r = -0.367; P < 0.05). CONCLUSIONS: We demonstrated that aerobic
      exercise training significantly decreased plasma ADMA concentrations with
      increase in carotid arterial compliance in postmenopausal women. These results
      suggest that reduction in ADMA may play an important role in the aerobic exercise
      training-induced increase in arterial compliance.

PMID- 24280042
TI  - Diacylglycerol kinase zeta limits the generation of natural regulatory T cells.
AB  - Natural regulatory T (nT(reg)) cells are important for maintaining tolerance to
      self- and foreign antigens, and they are thought to develop from thymocytes that
      receive strong T cell receptor (TCR)-mediated signals in the thymus. TCR
      engagement leads to the activation of phospholipase C-gamma1, which generates the
      lipid second messenger diacylglycerol (DAG) from phosphatidylinositol 4,5
      bisphosphate. We used mice that lack the zeta isoform of DAG kinase (DGKzeta),
      which metabolizes DAG to terminate its signaling, to enhance TCR-mediated
      signaling and identify critical signaling events in nT(reg) cell development.
      Loss of DGKzeta resulted in increased numbers of thymic CD25(+)Foxp3(-)CD4(+)
      nT(reg) cell precursors and Foxp3(+)CD4(+) nT(reg) cells in a cell-autonomous
      manner. DGKzeta-deficient T cells exhibited increased nuclear translocation of
      the nuclear factor kappaB subunit c-Rel, as well as enhanced extracellular signal
      regulated kinase (ERK) phosphorylation in response to TCR stimulation, suggesting
      that these downstream pathways may contribute to nT(reg) cell development.
      Indeed, reducing c-Rel abundance or blocking ERK phosphorylation abrogated the
      increased generation of nTreg cells by DGKzeta-deficient thymocytes. The extent
      of ERK phosphorylation correlated with TCR-mediated acquisition of Foxp3 in
      immature thymocytes in vitro. Furthermore, the development of nT(reg) cells was
      augmented in mice in which ERK activation was selectively enhanced in T cells.
      Together, these data suggest that DGKzeta regulates the development of nT(reg)
      cells by limiting the extent of activation of the ERK and c-Rel signaling
      pathways.

PMID- 24280043
TI  - The zeta isoform of diacylglycerol kinase plays a predominant role in regulatory
      T cell development and TCR-mediated ras signaling.
AB  - Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor
      (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol
      kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA)
      and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms
      are DGKalpha and DGKzeta, and deletion of the genes encoding either isoform
      enhances DAG-mediated signaling. We found that DGKzeta, but not DGKalpha,
      suppressed the development of natural regulatory T (T(reg)) cells and
      predominantly mediated Ras and Akt signaling downstream of the TCR. The
      differential functions of DGKalpha and DGKzeta were not attributable to
      differences in protein abundance in T cells or in their localization to the
      contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG
      mediated activator of Ras signaling, associated to a greater extent with DGKzeta
      than with DGKalpha; however, in silico modeling of TCR-stimulated Ras activation
      suggested that a difference in RasGRP1 binding affinity was not sufficient to
      cause differences in the functions of each DGK isoform. Rather, the model
      suggested that a greater catalytic rate for DGKzeta than for DGKalpha might lead
      to DGKzeta exhibiting increased suppression of Ras-mediated signals compared to
      DGKalpha. Consistent with this notion, experimental studies demonstrated that
      DGKzeta was more effective than DGKalpha at catalyzing the metabolism of DAG to
      PA after TCR stimulation. The enhanced effective enzymatic production of PA by
      DGKzeta is therefore one possible mechanism underlying the dominant functions of
      DGKzeta in modulating T(reg) cell development.

PMID- 24280045
TI  - Overexpression of constitutively active mitogen activated protein kinase kinase 6
      enhances tolerance to salt stress in rice.
AB  - BACKGROUND: Salinity is one of the most common abiotic stresses encountered by
      plants in the environment and transgenic approaches offer new opportunities to
      improve tolerance. The mitogen activated protein kinase (MAPK) kinase (MKK) is a
      key component of MAPK cascade that plays important roles in intra and extra
      cellular signaling in plants. In the present study, a MKK from rice (Oryza
      sativa), OsMKK6 was functionally characterized in salt stress by transforming its
      constitutively active form. FINDINGS: OsMKK6 was made constitutively active by
      mutating serine and threonine to glutamic acid by site directed mutagenesis, and
      transformed in indica cultivar rice var. Pusa Basmati-1. The transgenic seedlings
      growing in 200 mM NaCl solution showed increased root/shoot length and weight,
      less chlorophyll beaching and higher MAPK activity compared to the wild types.
      CONCLUSION: Present work suggest role of OsMKK6 gene in salt stress signaling in
      rice.

PMID- 24280044
TI  - Activated lymphocytes as a metabolic model for carcinogenesis.
AB  - Metabolic reprogramming is a key event in tumorigenesis to support cell growth,
      and cancer cells frequently become both highly glycolytic and glutamine
      dependent. Similarly, T lymphocytes (T cells) modify their metabolism after
      activation by foreign antigens to shift from an energetically efficient oxidative
      metabolism to a highly glycolytic and glutamine-dependent metabolic program. This
      metabolic transition enables T cell growth, proliferation, and differentiation.
      In both activated T cells and cancer cells metabolic reprogramming is achieved by
      similar mechanisms and offers similar survival and cell growth advantages.
      Activated T cells thus present a useful model with which to study the development
      of tumor metabolism. Here, we review the metabolic similarities and distinctions
      between activated T cells and cancer cells, and discuss both the common signaling
      pathways and master metabolic regulators that lead to metabolic rewiring.
      Ultimately, understanding how and why T cells adopt a cancer cell-like metabolic
      profile may identify new therapeutic strategies to selectively target tumor
      metabolism or inflammatory immune responses. 

PMID- 24280046
TI  - Narrowing down the targets for yield improvement in rice under normal and abiotic
      stress conditions via expression profiling of yield-related genes.
AB  - BACKGROUND: Crop improvement targeting high yield and tolerance to environmental
      stresses has become the need of the hour. Yield improvement via breeding or gene
      pyramiding aiming comprehensive incorporation of the agronomically favored traits
      requires an in-depth understanding of the molecular basis of these traits. The
      present study describes expression profiling of yield-related genes in rice with
      respect to different developmental stages and various abiotic stress conditions.
      RESULTS: Our analysis indicates developmental regulation of the yield-related
      genes pertaining to the genetic reprogramming involved at the corresponding
      developmental stage. The gene expression data can be utilized to specifically
      select particular genes which can potentially function synergistically for
      enhancing the yield while maintaining the source-sink balance. Furthermore, to
      gain some insights into the molecular basis of yield penalty during various
      abiotic stresses, the expression of selected yield-related genes has also been
      analyzed by qRT-PCR under such stress conditions. Our analysis clearly showed a
      tight transcriptional regulation of a few of these yield-related genes by abiotic
      stresses. The stress-responsive expression patterns of these genes could explain
      some of the most important stress-related physiological manifestations such as
      reduced tillering, smaller panicles and early completion of the life cycle owing
      to reduced duration of vegetative and reproductive phases. CONCLUSIONS:
      Development of high yielding rice varieties which maintain their yield even under
      stress conditions may be achieved by simultaneous genetic manipulation of certain
      combination of genes such as LRK1 and LOG, based on their function and expression
      profile obtained in the present study. Our study would aid in investigating in
      future, whether over-expressing or knocking down such yield-related genes can
      improve the grain yield potential in rice.

PMID- 24280047
TI  - High performance multi-spectral interrogation for surface plasmon resonance
      imaging sensors.
AB  - Surface plasmon resonance (SPR) sensing has proven to be a valuable tool in the
      field of surface interactions characterization, especially for biomedical
      applications where label-free techniques are of particular interest. In order to
      approach the theoretical resolution limit, most SPR-based systems have turned to
      either angular or spectral interrogation modes, which both offer very accurate
      real-time measurements, but at the expense of the 2-dimensional imaging
      capability, therefore decreasing the data throughput. In this article, we show
      numerically and experimentally how to combine the multi-spectral interrogation
      technique with 2D-imaging, while finding an optimum in terms of resolution,
      accuracy, acquisition speed and reduction in data dispersion with respect to the
      classical reflectivity interrogation mode. This multi-spectral interrogation
      methodology is based on a robust five parameter fitting of the spectral
      reflectivity curve which enables monitoring of the reflectivity spectral shift
      with a resolution of the order of ten picometers, and using only five wavelength
      measurements per point. In fine, such multi-spectral based plasmonic imaging
      system allows biomolecular interaction monitoring in a linear regime
      independently of variations of buffer optical index, which is illustrated on a
      DNA-DNA model case. 

PMID- 24280048
TI  - A new platform for sensing urinary morphine based on carrier assisted
      electromembrane extraction followed by adsorptive stripping voltammetric
      detection on screen-printed electrode.
AB  - Electromembrane extraction (EME) coupled with electrochemical detection on screen
      printed carbon electrode has been developed for the quantification of morphine in
      urine samples. Charged morphine molecules were extracted from an aqueous sample
      by applying an electrical potential through a thin supported liquid membrane
      (SLM) into an acidic aqueous acceptor solution (20 uL) placed inside the lumen of
      a hollow fiber. Then, the acceptor solution was mixed with 20 uL of NaOH solution
      (0.1 M) and analyzed using screen printed electrochemical strip. Differential
      pulse voltammetry (DPV) peak current at 0.18 V was selected as the signal and the
      influences of experimental parameters were investigated and optimized using Box
      behnken design and also one-variable-at-a-time methodology as follows: adsorptive
      accumulation time, 40 s; SLM, 2-nitrophenyl octyl ether+10% tris-(2-ethylhexyl)
      phosphate+10% di-(2-ethylhexyl) phosphate; pH of the sample solution, 6.0; pH of
      the acceptor solution, 1.0; EME time, 24 min; EME potential, 90 V and stirring
      rate, 1000 rpm. The calibration curve which was plotted by the variation of DPV
      currents as a function of morphine concentration was linear within the range of
      0.005-2.0 ug mL(-1). The limit of detection and the limit of quantification were
      0.0015 (S/N=3) and 0.005 ug mL(-1), respectively. Finally, the proposed method
      was able to determine morphine simply and effectively at concentration levels
      encountered in toxicology and doping.

PMID- 24280049
TI  - Aptamer cocktails: enhancement of sensing signals compared to single use of
      aptamers for detection of bacteria.
AB  - Microbial cells have many binding moieties on their surface for binding to their
      specific bioreceptors. The whole-cell SELEX process enables the isolation of
      various aptamers that can bind to different components on the cell surface such
      as proteins, polysaccharides, or flagella with high affinity and specificity.
      Here, we examine the binding capacity of an aptamer mixture (aptamer cocktail)
      composed of various combinations of 3 different DNA aptamers isolated from
      Escherichia coli and compare it with one of the single aptamers using
      fluorescence-tagged aptamers. The aptamer mixtures showed higher fluorescence
      signal than did any single aptamer used, which suggests that use of aptamer
      mixtures can enhance the sensitivity of detection of microbial cells. To further
      evaluate this effect, the signal enhancement and improvement of sensitivity
      provided by combinatorial use of aptamers were examined in an electrochemical
      detection system. With regard to current decreases, the aptamer cocktail
      immobilized on gold electrodes performed better than a single aptamer immobilized
      on gold electrodes did. Consequently, the detection limit achieved using the
      aptamers individually was approximately 18 times that when the 3 aptamers were
      used in combination. These results support the use of aptamer cocktails for
      detection of complex targets such as E. coli with enhanced sensitivity. 

PMID- 24280050
TI  - A cost-effective sandwich electrochemiluminescence immunosensor for
      ultrasensitive detection of HIV-1 antibody using magnetic molecularly imprinted
      polymers as capture probes.
AB  - In this report, a rapid and cost-effective sandwich electrochemiluminescence
      (ECL) immunosensor was constructed for the ultrasensitive detection of human
      immunodeficiency virus type 1 antibody (anti-HIV-1) using magnetic molecularly
      imprinted polymers (MMIPs) as capture probes by combining surface and epitope
      imprinting techniques and antigen conjugated with horseradish peroxidase (HRP-HIV
      1) as labels. First, 3-aminobenzeneboronic acid (APBA) was used as the functional
      monomer and cross-linking reagent, which was polymerized on the surface of
      silicate-coated magnetic iron oxide nanoparticles (Fe3O4@SiO2 NPs) in the
      presence of human immunoglobulin G (HIgG), as the template exhibiting the same Fc
      region but different Fab region to anti-HIV-1 after the addition of the
      initiator, ammonium persulfate. This process resulted in grafting a hydrophilic
      molecularly imprinted polymer (MIP) film on the Fe3O4@SiO2 NPs. Thus, MMIPs,
      which could be reused after eluting the template, were used to recognize and
      enrich ultra-trace levels of anti-HIV-1. Subsequently, a novel sandwich ECL
      immunosensor was formed through the immunoreaction between MMIPs conjugated with
      varied concentrations of anti-HIV-1 and HRP-HIV-1. By the catalysis of HRP
      immobilized onto HRP-HIV-1 on the ECL system of Luminol-H2O2, a linear response
      range of the anti-HIV-1 dilution ratio (standard positive serum) was achieved
      from 1:20,000 to 1:50, with a detection limit of 1:60,000 (S/N=3). The developed
      method provides a low-cost, simple, and sensitive way for the early diagnosis of
      HIV infected patients. 

PMID- 24280051
TI  - FRET-based dimeric aptamer probe for selective and sensitive Lup an 1 allergen
      detection.
AB  - A sensitive method for the rapid and sensitive detection of the anaphylactic food
      allergen Lup an 1 (beta-conglutin) exploiting fluorescence resonance energy
      transfer (FRET) has been developed. A high affinity dimeric form of a truncated
      11-mer aptamer against beta-conglutin was used, with each monomeric aptamer being
      flanked by donor/acceptor moieties. The dimeric form in the absence of target
      yields fluorescence emission due to the FRET from the excited fluorophore to the
      proximal second fluorophore. However, upon addition of beta-conglutin, the
      specific interaction induces a change in the bi-aptameric structure resulting in
      an increase in fluorescence emission. The method is highly specific and
      sensitive, with a detection limit of 150 pM, providing an effective tool for the
      direct detection of the toxic beta-conglutin subunit in foodstuffs in just 1 min
      at room temperature.

PMID- 24280052
TI  - Slowly released molasses barrier system for controlling nitrate plumes in
      groundwater: a pilot-scale tank study.
AB  - A well-type barrier system containing solidified molasses as a reactive medium
      was developed to promote the indigenous denitrifying activity and to treat
      nitrate plumes in groundwater. Three slowly released molasses (SRM) barrier
      systems harboring 60, 120, and 120 SRM rods, which were named System A, B, and C,
      respectively, were operated to examine nitrate removal efficiency in a pilot
      scale sandy tank. These SRM systems induced a consistent removal of nitrate
      without pore clogging and hydraulic disturbance during the test period. The
      initial nitrate concentration was 142mgL(-1), and the concentrations decreased by
      80%, 84%, and 79% in System A, B, and C, respectively. In particular, System C
      was inoculated with heterotrophic denitrifiers, but the nitrate removal
      efficiency was not enhanced compared to System B, probably due to the prior
      existence of indigenous denitrifiers in the sandy tank. The presence of nitrite
      reductase-encoding gene (i.e. nirK) at the site was confirmed by denatured
      gradient gel electrophoresis analysis. 

PMID- 24280053
TI  - Equilibrium and kinetics studies of arsenate adsorption by FePO(4).
AB  - The present work is focusing on removal of arsenate from aqueous solution using
      FePO4. The equilibrium study regarding the removal of arsenic by FePO4 was
      carried out at 298, 308, 318 and 328K. Langmuir parameters were found to increase
      with the increase in temperature indicating that the adsorption is favorable at
      high temperature. Kinetic study of arsenate adsorption on FePO4 was also carried
      out at different temperatures and at pH 6 and 8. Different kinetic models were
      used to the kinetic data amongst which pseudo second order model was best fitted.
      The mechanism of the adsorption kinetics was investigated by employing
      intraparticle diffusion and Richenberg models. The energy of activation (Ea) was
      found to be 30 and 35.52kJmol(-1) at pH 6 and pH 8, respectively, suggesting
      chemisorption nature of the adsorption process. The negative entropic values of
      activation signified the existence of entropy barrier while the positive
      DeltaG(#) values indicated the existence of energy barrier to be crossed over for
      the occurrence of a chemical reaction. Both the spectroscopic studies and
      increase in equilibrium pH reveal the anion exchange removal of arsenate from
      aqueous solution to the solid surface. 

PMID- 24280054
TI  - Plutonium partitioning in three-phase systems with water, colloidal particles,
      and granites: new insights into distribution coefficients.
AB  - The traditional sorption experiments commonly treated the colloid-associated
      species of low-solubility contaminants as immobile species resulted from the
      centrifugation or ultrafiltration, and then solid/liquid distribution
      coefficients (Ks/d) were determined. This may lead to significantly
      underestimated mobility of the actinides in subsurface environments. Accordingly,
      we defined a new distribution coefficient (Ks/d+c) to more adequately describe
      the mobile characteristics of colloidal species. The results show that under
      alkaline aqueous conditions the traditional Ks/d was 2-3 orders of magnitude
      larger than the Ks/d+c involving the colloidal species of (239)Pu. The
      colloid/liquid distribution coefficients Kc/d?0 (~10(6)mL/g) revealed strong
      competition of the colloidal granite particles with the granite grains for Pu.
      The distribution percentages of Pu in the three-phase systems, depending on
      various conditions such as particle concentrations, Na(+) concentrations, pH and
      time, were determined. Moreover, we developed the thermodynamic and kinetic
      complexation models to explore the interaction of Pu with the particle surfaces. 

PMID- 24280055
TI  - Impacts of different nanoparticles on functional bacterial community in activated
      sludge.
AB  - Rapidly developing industry raises concerns about the environmental impacts of
      nanoparticles, but the effects of inorganic nanoparticles on functional bacterial
      community in wastewater treatment remain unclear. The discriminated effects of
      silver nanoparticles (Ag-NP) and zinc oxide nanoparticles (ZnO-NP) in a simulated
      sequencing batch reactor (SBR) system were therefore evaluated by the RNA-based
      terminal restricted fragment length polymorphism (T-RFLP), 16S rcDNA gene clone
      library and real-time reverse transcription-PCR (RT-PCR) analyses. Although the
      COD and NH4-N removal efficiencies were not or slightly reduced by the addition
      of ZnO-NP and Ag-NP, the functional bacterial community changed remarkably. The
      denitrification related species were inhibited by high dosage of ZnO-NP and Ag
      NP, including Diaphorobacter species, Thauera species and those in the
      Sphaerotilus-Leptothrix group. However, the bacteria related to sludge bulking,
      heavy metal resistant and biosorption were increased, especially by ZnO-NPs
      treatment, including those closely related to Haliscomenobacter hydrossis,
      Zoogloea ramigera and Methyloversatilis universalis. In addition, Ag-NP and ZnO
      NP treatments influenced the functional bacterial community differently.
      Increasing of bulking related bacteria may help to compensate the COD removal
      efficiency and to maintain functional redundancy, but could lead to operation
      failure of activated sludge system when expose to ZnO-NPs. 

PMID- 24280056
TI  - Testosterone replacement ameliorates nonalcoholic fatty liver disease in
      castrated male rats.
AB  - Nonalcoholic fatty liver disease is common in developed countries and is
      associated with obesity, metabolic syndrome, and type 2 diabetes. T deficiency is
      a risk factor for developing these metabolic deficiencies, but its role in
      hepatic steatosis has not been well studied. We investigated the effects of T on
      the pathogenesis of hepatic steatosis in rats fed a high-fat diet (HFD). Adult
      male rats were randomly placed into four groups and treated for 15 weeks: intact
      rats on regular chow diet (RCD), intact rats on liquid HFD (I+HFD), castrated
      rats on HFD (C+HFD), and castrated rats with T replacement on HFD (C+HFD+T). Fat
      contributed 71% energy to the HFD but only 16% of energy to the RCD. Serum T
      level was undetectable in castrated rats, and T replacement led to 2-fold higher
      mean serum T levels than in intact rats. C+HFD rats gained less weight but had
      higher percentage body fat than C+HFD+T. Severe micro- and macrovesicular fat
      accumulated in hepatocytes with multiple inflammatory foci in the livers of
      C+HFD. I+HFD and C+HFD+T hepatocytes demonstrated only mild to moderate
      microvesicular steatosis. T replacement attenuated HFD-induced hepatocyte
      apoptosis in castrated rats. Serum glucose and insulin levels were not increased
      with HFD in any group. Immunoblots showed that insulin-regulated proteins were
      not changed in any group. This study demonstrates that T deficiency may
      contribute to the severity of hepatic steatosis and T may play a protective role
      in hepatic steatosis and nonalcoholic fatty liver disease development without
      insulin resistance. 

PMID- 24280057
TI  - A novel hormone is required for the development of reproductive phenotypes in
      adult female crabs.
AB  - The crustacean male-specific androgenic hormone is widely accepted as a key
      factor in sexual differentiation and in the development of secondary sex
      characteristics. However, the mechanism by which the plethora of different
      reproductive strategies are controlled and executed in crustaceans is not known.
      We discovered in the blue crab, Callinectes sapidus, a hitherto unknown
      neurohormone, named crustacean female sex hormone (CFSH), in distinct
      neurosecretory cells in the eyestalk ganglia. CFSH is highly expressed in females
      but weakly in males, and its crucial role in developing adult female phenotypes
      has now been established. CFSH cDNA encodes a 225-amino acid (aa) novel protein
      composed of a 23-aa predicted signal peptide, 33-aa precursor-related peptide and
      167-aa mature protein that did not match any other sequence in GenBank. CFSH RNA
      interference knockdown by multiple administrations of double-stranded RNA at the
      prepubertal stage causes abnormal development of brooding and mating systems upon
      puberty. These systems include a pair of gonopores and an egg attachment system
      for brooding, comprised of an enlarged semicircular abdomen and ovigerous setae.
      The ovigerous setae in CFSH knocked-down females were fewer and 50% shorter and
      the gonopores were either significantly smaller than those of controls,
      misplaced, or absent. We also identified CFSH in the green crab, Carcinus maenas,
      a species that shares a similar reproductive strategy with C. sapidus. Together,
      our data provide the first evidence for the presence of a female hormone in
      crustaceans and its importance in positively controlling anatomic features
      associated with brooding and mating systems. From an evolutionary standpoint, the
      endocrine control supporting a female-specific reproductive strategy, as
      previously described for many vertebrate species, has now been demonstrated for
      the first time in crustaceans. 

PMID- 24280058
TI  - LGR4 and its ligands, R-spondin 1 and R-spondin 3, regulate food intake in the
      hypothalamus of male rats.
AB  - The hypothalamus plays a key role in the regulation of feeding behavior. Several
      hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular
      nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in
      energy homeostasis. Analysis of microarray data derived from ARC revealed that
      leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly
      expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors.
      Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4
      subfamily. In the present study, we investigated the distribution and function of
      LGR4-LGR6 and Rspos (1-4) in the brain of male rat. In situ hybridization showed
      that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus.
      LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived
      neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization;
      LGR6 is only expressed in the epithelial lining of the lower portion of the third
      ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated
      with fasting. Rspo3 is expressed in the paraventricular nucleus and also down
      regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD,
      indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into
      the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y
      and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is
      up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their
      receptor LGR4 form novel circuits in the brain to regulate energy homeostasis. 

PMID- 24280061
TI  - EMPeror: a tool for visualizing high-throughput microbial community data.
AB  - BACKGROUND: As microbial ecologists take advantage of high-throughput sequencing
      technologies to describe microbial communities across ever-increasing numbers of
      samples, new analysis tools are required to relate the distribution of microbes
      among larger numbers of communities, and to use increasingly rich and standards
      compliant metadata to understand the biological factors driving these
      relationships. In particular, the Earth Microbiome Project drives these needs by
      profiling the genomic content of tens of thousands of samples across multiple
      environment types. FINDINGS: Features of EMPeror include: ability to visualize
      gradients and categorical data, visualize different principal coordinates axes,
      present the data in the form of parallel coordinates, show taxa as well as
      environmental samples, dynamically adjust the size and transparency of the
      spheres representing the communities on a per-category basis, dynamically scale
      the axes according to the fraction of variance each explains, show, hide or
      recolor points according to arbitrary metadata including that compliant with the
      MIxS family of standards developed by the Genomic Standards Consortium, display
      jackknifed-resampled data to assess statistical confidence in clustering, perform
      coordinate comparisons (useful for procrustes analysis plots), and greatly reduce
      loading times and overall memory footprint compared with existing approaches.
      Additionally, ease of sharing, given EMPeror's small output file size, enables
      agile collaboration by allowing users to embed these visualizations via emails or
      web pages without the need for extra plugins. CONCLUSIONS: Here we present
      EMPeror, an open source and web browser enabled tool with a versatile command
      line interface that allows researchers to perform rapid exploratory
      investigations of 3D visualizations of microbial community data, such as the
      widely used principal coordinates plots. EMPeror includes a rich set of
      controllers to modify features as a function of the metadata. By being
      specifically tailored to the requirements of microbial ecologists, EMPeror thus
      increases the speed with which insight can be gained from large microbiome
      datasets.

PMID- 24280059
TI  - Vitamin D signaling regulates proliferation, differentiation, and myotube size in
      C2C12 skeletal muscle cells.
AB  - Vitamin D deficiency is linked to a range of muscle disorders including myalgia,
      muscle weakness, and falls. Humans with severe vitamin D deficiency and mice with
      transgenic vitamin D receptor (VDR) ablation have muscle fiber atrophy. However,
      molecular mechanisms by which vitamin D influences muscle function and fiber size
      remain unclear. A central question is whether VDR is expressed in skeletal muscle
      and is able to regulate transcription at this site. To address this, we examined
      key molecular and morphologic changes in C2C12 cells treated with 25
      hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D). As well as
      stimulating VDR expression, 25(OH)D and 1,25(OH)(2)D dose-dependently increased
      expression of the classic vitamin D target cytochrome P450, family 24, subfamily
      A, polypeptide 1 (CYP24A1), demonstrating the presence of an autoregulatory
      vitamin D-endocrine system in these cells. Luciferase reporter studies
      demonstrated that cytochrome P450, family 27, subfamily B, polypeptide 1
      (CYP27B1) was functional in these cells. Both 25OHD and 1,25(OH)(2)D altered
      C2C12 proliferation and differentiation. These effects were related to the
      increased expression of genes involved in G(0)/G(1) arrest (retinoblastoma
      protein [Rb], 1.3-fold; ATM, 1.5-fold, both P < .05), downregulation of mRNAs
      involved in G(1)/S transition, including myc and cyclin-D1 (0.7- and 0.8-fold,
      both P < .05) and reduced phosphorylation of Rb protein (0.3-fold, P < .005).
      After serum depletion, 1,25(OH)(2)D (100nM) suppressed myotube formation with
      decreased mRNAs for key myogenic regulatory factors (myogenin, 0.5-fold; myf5,
      0.4-fold, P < .005) but led to a 1.8-fold increase in cross-sectional size of
      individual myotubes associated with markedly decreased myostatin expression (0.2
      fold, P < .005). These data show that vitamin D signaling alters gene expression
      in C2C12 cells, with effects on proliferation, differentiation, and myotube size.

PMID- 24280062
TI  - Olfaction, pheromones and life.
AB  - BACKGROUND: From an evolutionary standpoint, olfaction is one of the oldest
      senses, and one that affects all aspects of life. This review discusses the
      influence of olfaction and pheromones on life. METHODS: A literature search was
      conducted using MEDLINE (1966-2012), Embase (1988-2012), The Cochrane Library
      (1993-2013) and Ovid (1966-2012). RESULTS: Olfaction plays an important role in
      life, from infancy through to adulthood and declining health in old age. Culture,
      memories and emotions, which add to life's complexity and overall enjoyment, are
      also influenced by olfaction. CONCLUSION: Olfaction has a chronological influence
      on life, affecting all aspects from the cradle to the grave; it plays a role in
      the quality of life as a key ingredient of human evolution, survival and
      enjoyment.

PMID- 24280063
TI  - [The implementation of clinical guidelines improves the appropriateness of
      antibiotic prescribing].

PMID- 24280064
TI  - [Spontaneous bacteremia due to Campylobacter coli in a cirrhotic patient].

PMID- 24280065
TI  - Extrasensory perception: odorant and taste receptors beyond the nose and mouth.
AB  - G protein-coupled receptors (GPCRs) represent the largest family of transmembrane
      receptors and are prime therapeutic targets. The odorant and taste receptors
      account for over half of the GPCR repertoire, yet they are generally excluded
      from large-scale, drug candidate analyses. Accumulating molecular evidence
      indicates that the odorant and taste receptors are widely expressed throughout
      the body and functional beyond the oronasal cavity - with roles including
      nutrient sensing, autophagy, muscle regeneration, regulation of gut motility,
      protective airway reflexes, bronchodilation, and respiratory disease. Given this
      expanding array of actions, the restricted perception of these GPCRs as mere
      mediators of smell and taste is outdated. Moreover, delineation of the precise
      actions of odorant and taste GPCRs continues to be hampered by the relative
      paucity of selective and specific experimental tools, as well as the lack of
      defined receptor pharmacology. In this review, we summarize the evidence for
      expression and function of odorant and taste receptors in tissues beyond the nose
      and mouth, and we highlight their broad potential in physiology and
      pathophysiology. 

PMID- 24280066
TI  - Integration of molecular targeted therapy with radiation in head and neck cancer.
AB  - Approximately 600,000 new cases of head and neck cancer arise worldwide each
      year. Of these, a large majority are head and neck squamous cell carcinomas
      (HNSCC). Conventional treatments, including surgical excision followed by
      radiation and/or chemoradiotherapy have limited efficacy and are associated with
      substantial toxicity. To date, key targets for molecular targeted therapy in
      HNSCC are epidermal growth factor receptors and angiogenesis-related factors.
      Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor
      (EGFR) and it is the only targeted therapy approved by the United States Food and
      Drug Administration for the treatment of HNSCC. Cetuximab in combination with
      radiotherapy represents a standard approach for newly diagnosed patients who are
      unable to tolerate platinum chemotherapy. Despite efficacy in preclinical HNSCC
      models, cetuximab is only effective in a subset of HNSCC patients, most likely
      due to the high heterogeneity of this cancer. Additional targets under active
      investigation include the PI3K/Akt pathway, the Ras-MAPK-ERK pathway and the
      JAK/STAT pathway, among others. Combining molecular targeted therapies and
      radiation may allow for deintensification of radiotherapy thereby reducing
      radiation toxicities and improving treatment outcomes. Here we review the
      preclinical and clinical data in support of treatment strategies that combined
      targeted therapy with radiation in HNSCC. 

PMID- 24280067
TI  - Exercise training initiated in late middle age attenuates cardiac fibrosis and
      advanced glycation end-product accumulation in senescent rats.
AB  - While it has long been postulated that exercise training attenuates the age
      related decline in heart function normally associated with increased fibrosis and
      collagen cross-linking, the potential benefits associated with exercise training
      initiated later in life are currently unclear. To address this question, Fischer
      344 * Brown Norway F1 rats underwent treadmill-based exercise training starting
      in late middle age and continued into senescence (35 mo) and were compared with
      age-matched sedentary rats. Hearts were examined for fibrosis and advanced
      glycation end-products in the subendocardial layer of left ventricular cross
      sections. Genes for collagen synthesis and degradation were assessed by
      polymerase chain reaction, and matrix metalloproteinase (MMP) activity was
      assessed by EnzChek(r) Gelatinase/Collagenase Assay Kit. Exercise training of
      late middle-aged rats attenuated fibrosis and collagen cross-linking, while also
      reducing age-related mortality between late middle age and senescence. This
      training was also associated with an attenuated advanced glycation end-product
      (AGE) accumulation with aging, suggesting a decrease in collagen cross-linking.
      Conversely, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene
      expression, TIMP and MMP1 protein expression, and MMP activity increased with age
      but were not significantly impacted by exercise training. While our results
      demonstrate that exercise training in late middle age attenuates age-related
      mortality and cardiac fibrosis and is accompanied by attenuated AGE accumulation
      indicative of less collagen cross-linking, the mechanisms explaining this
      attenuated replacement fibrosis did not appear to involve altered TIMP1
      expression, or MMP protein and activity.

PMID- 24280068
TI  - Imatinib analogs as potential agents for PET imaging of Bcr-Abl and c-KIT
      expression at a kinase level.
AB  - We synthesized two series of imatinib mesylate (STI-571) analogs to develop a Bcr
      Abl and c-KIT receptor-specific labeling agent for positron emission tomography
      (PET) imaging to measure Bcr-Abl and c-KIT expression levels in a mouse model.
      The methods of molecular modeling, synthesis of STI-571 and its analogs, in vitro
      kinase assays, and radiolabeling are described. Molecular modeling revealed that
      these analogs bind the same Bcr-Abl and c-KIT binding sites as those bound by STI
      571. The analogs potently inhibit the tyrosine kinase activity of Bcr-Abl and c
      KIT, similarly to STI-571. [(18)F]-labeled STI-571 was prepared with high
      specific activity (75 GBq/MUmol) by nucleophilic displacement and an average
      radiochemical yield of 12%. [(131)I]-labeled STI-571 was prepared with high
      purity (>95%) and an average radiochemical yield of 23%. The uptake rates of
      [(18)F]-STI-571 in K562 cells expressing Abl and in U87WT cells overexpressing c
      KIT were significantly higher than those in the U87 cell and could be inhibited
      by STI-71 (confirming the specificity of uptake). PET scans of K562 and U87WT
      tumor-bearing mice with [(18)F]-STI-571 as a contrast agent showed visible tumor
      uptake and tumor-to-non-target contrast.

PMID- 24280069
TI  - Curcumin glucuronides: assessing the proliferative activity against human cell
      lines.
AB  - A gram scale synthesis of the glucuronide metabolites of curcumin were completed
      in four steps. The newly synthesized curcumin glucuronide compounds 2 and 3 along
      with curcumin 1 were tested and their anti-proliferative effects against KBM-5,
      Jurkat cell, U266, and A549 cell lines were reported. Biological data revealed
      that as much as 1 MUM curcumin 1 exhibited anticancer activity and almost 100%
      cell kill was noted at 10 MUM on two out of four cell lines; while curcumin mono
      glucuronide 2 as well as di-glucuronide 3 displayed no suppression of cell
      proliferation.

PMID- 24280070
TI  - New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as
      sugar moiety; synthesis, X-ray crystallography and anticancer activity.
AB  - An amine group was synthesized starting from an optically active
      bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of
      a key 6-chloropurine intermediate. This was then reacted with ammonia and
      selected amines obtaining new adenine- and 6-substituted adenine conformationally
      constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane
      skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of
      base to the ring and a L configuration of the nucleoside analogues. The compounds
      were tested for anticancer activity. 

PMID- 24280072
TI  - Chronic ammonia exposure does not influence hepatic gene expression in growing
      pigs.
AB  - Housed pigs are often exposed to elevated concentrations of atmospheric ammonia.
      This aerial pollutant is widely considered to be an environmental stressor that
      also predisposes to reduced growth rates and poor health, although evidence to
      support this view is limited. Hepatic gene expression is very responsive to
      stress and metabolic effects. Two batches of growing pigs were therefore exposed
      to a nominal concentration of atmospheric ammonia of either 5 ppm (low) or 20 ppm
      (high) from 4 weeks of age for 15 weeks. Growth rates were monitored. Samples of
      liver were taken after slaughter (at ~19 weeks of age). Samples from the second
      batch were analysed for global gene expression using 23 K Affymetrix GeneChip
      porcine genome arrays. Samples from both batches were subsequently tested for
      five candidate genes using quantitative real-time PCR (qPCR). The array analysis
      failed to detect any significant changes in hepatic gene expression following
      chronic exposure to atmospheric ammonia. Animals clustered into two main groups
      but this was not related to the experimental treatment. There was also no
      difference in growth rates between groups. The qPCR analyses validated the array
      results by showing similar fold changes in gene expression to the arrays. They
      revealed a significant batch effect in expression of lipin 1 (LPIN1), Chemokine
      (C-X-C motif) ligand 14 (CXCL14), serine dehydratase (SDS) and hepcidin
      antimicrobial peptide (HAMP). Only CXCL14, a chemotactic cytokine for monocytes,
      was significantly down-regulated in response to ammonia. As chronic exposure to
      atmospheric ammonia did not have a clear influence on hepatic gene expression,
      this finding implies that 20 ppm of atmospheric ammonia did not pose a
      significant material risk to the health or metabolism of housed pigs.

PMID- 24280073
TI  - The long and winding road to the mitochondrial pyruvate carrier.
AB  - The extraction of energy and biosynthetic building blocks from fuel metabolism is
      a fundamental requisite for life. Through the action of cellular enzymes, complex
      carbon structures are broken down in reactions coupled to the production of high
      energy phosphates as in ATP and GTP as well as electron carriers such as NADH and
      FADH2. These processes traverse across compartments inside the cell in order to
      access specific enzymes and environments. Pyruvate is the end product of
      cytosolic glycolysis and has a variety of possible fates, the major one being
      mitochondrial oxidation. While this metabolite has been known to cross the inner
      mitochondrial membrane for decades, it is only recently that proteins necessary
      for this activity have been identified. This review will chronicle more than 40
      years of research interrogating this critical process and will discuss some of
      the possible implications of this discovery for cancer metabolism. 

PMID- 24280074
TI  - Loss of microRNA-200a expression correlates with tumor progression in breast
      cancer.
AB  - MicroRNAs (miRNAs) are 19~22 nucleotide-long, noncoding, small RNAs, involved in
      post-transcriptional regulation of many target genes. The miRNA-200 family has
      been shown to play a crucial role in the epithelial to mesenchymal transition in
      human cancers. In situ hybridization (ISH) was used to investigate the expression
      level of miRNA-200a in breast cancers. Formalin-fixed, paraffin embedded (FFPE)
      tissues from normal breast, ductal carcinoma in situ (DCIS), primary cancers, and
      metastatic lymph nodes were achieved and constructed to tissue microarrays. MiRNA
      200a expression was demonstrated in 95.2% of normal breast tissue samples and
      80.4% of DCIS, whereas 178 (58.0%) of 307 breast cancers and 83.3% of metastatic
      lymph node samples lacked miRNA-200a expression (P < 0.001). Moreover, loss of
      MiRNA-200a expression correlated with high histologic grade (P = 0.017) and
      perinodal tumor extension (P = 0.026). However, miRNA-200a expression did not
      predict tumor recurrence or patient survival. In conclusion, loss of miRNA-200a
      is frequently observed in breast cancers, especially tumors with high grade
      histology. These findings suggest that miRNA-200a may play an important role in
      breast cancer initiation and progression. ISH can be used to detect miRNAs in
      FFPE sections, and should permit the validation of miRNAs as biomarkers in large
      clinical samples. 

PMID- 24280071
TI  - Spontaneous Network Activity and Synaptic Development.
AB  - Throughout development, the nervous system produces patterned spontaneous
      activity. Research over the past two decades has revealed a core group of
      mechanisms that mediate spontaneous activity in diverse circuits. Many circuits
      engage several of these mechanisms sequentially to accommodate developmental
      changes in connectivity. In addition to shared mechanisms, activity propagates
      through developing circuits and neuronal pathways (i.e., linked circuits in
      different brain areas) in stereotypic patterns. Increasing evidence suggests that
      spontaneous network activity shapes synaptic development in vivo Variations in
      activity-dependent plasticity may explain how similar mechanisms and patterns of
      activity can be employed to establish diverse circuits. Here, I will review
      common mechanisms and patterns of spontaneous activity in emerging neural
      networks and discuss recent insights into their contribution to synaptic
      development. 

PMID- 24280075
TI  - [A rare case of two mechanisms of prosthetic valve dysfunction in the same
      patient].
AB  - Prosthetic valve dysfunction is a significant clinical event. Determining its
      etiological mechanism and severity can be difficult. The authors present the case
      of a 50-year-old man, with two mechanical valve prostheses in aortic and mitral
      positions, hospitalized for decompensated heart failure. He had a long history of
      rheumatic multivalvular disease and had undergone three heart surgeries. On
      admission, investigation led to a diagnosis of severe dysfunction of both
      mechanical prostheses with different etiologies and mechanisms: pannus formation
      in the prosthetic aortic valve and intermittent dysfunction of the mitral
      prosthesis due to interference of a ruptured chorda tendinea in closure of the
      disks. The patient was reoperated, leading to significant improvement in
      functional class. 

PMID- 24280076
TI  - Pathophysiology of pulmonary hypertension in newborns: therapeutic indications.
AB  - Failure of the normal cardiopulmonary transition can lead to persistent pulmonary
      hypertension of the newborn. Some degree of pulmonary hypertension complicates
      the course of more than 10% of all neonates with respiratory failure. This review
      article discusses the vascular abnormalities associated with neonatal pulmonary
      hypertension. Common therapies including inhaled nitric oxide, high frequency
      ventilation, surfactant, and extracorporeal life support are included. Promising
      new treatment approaches like phosphodiesterase inhibition and cell-targeted
      therapies are presented. 

PMID- 24280077
TI  - Echocardiographic diagnosis of ruptured right sinus of Valsalva.

PMID- 24280078
TI  - [Characterization of lipid profile in primary health care users in Portugal].
AB  - AIM: To characterize the distribution of total cholesterol (TC), LDL cholesterol
      (LDL-C), HDL cholesterol (HDL-C) and triglycerides in primary health care users.
      METHODS: We performed a cross-sectional study in a primary care setting,
      involving 719 general practitioners based on stratified distribution proportional
      to the population density of each region of Portugal. The first two adult
      patients scheduled for an appointment on a given day were invited to participate.
      A questionnaire was applied to assess sociodemographic, clinical and laboratory
      data including lipid profile. RESULTS: The study included 16 856 individuals
      (mean age 58.1+/-15.1 years; 61.6% women). Data on TC, LDL-C, HDL-C and
      triglycerides were available for 95.9% (n=16 159), 59.1% (n=9956), 95.4% (n=16
      074) and 97.9% (n=16 494) of the population, respectively. Hypercholesterolemia
      (TC >=200 mg/dl) was detected in 47%, and 38.4% had high levels of LDL-C (>=130
      mg/dl). Hypertriglyceridemia (>=200 mg/dl) and low HDL-C (<40 mg/dl) were less
      prevalent, affecting roughly 13% of the population. Dyslipidemia was more common
      in middle-aged men and in post-menopausal women. Of the population aged over 40,
      54.1% met eligibility criteria for lipid-lowering therapy and 44.7% were
      medicated with statins, but only 16.0% of these had TC <=175 mg/dl. CONCLUSIONS:
      Dyslipidemia is highly prevalent in primary health care users in Portugal. It is
      particularly common in middle-aged men and post-menopausal women, who should be
      considered target groups for preventive public health measures.

PMID- 24280079
TI  - [Remote versus face-to-face monitoring for implantable cardiac devices: rationale
      and design of the PORTLink (PORTuguese Research on Telemonitoring with CareLink)
      trial].
AB  - With expanding indications for cardiac implantable electronic devices (CIEDs)
      capable of treating bradycardias, complex cardiac tachyarrhythmias and heart
      failure, the number of patients requiring regular long-term specialized care is
      growing rapidly. Currently, routine face-to-face follow-up consultations for
      patients with CIEDs are a significant burden on hospital services. Remote
      telemonitoring appears to offer a safe and effective alternative to conventional
      follow-up in this area. The Medtronic CareLink Network enables remote monitoring
      of CIED patients, and thus has the potential to improve the efficiency of medical
      care in this population. The objective of the PORTLink (PORTuguese Research on
      Telemonitoring with CareLink) multicenter randomized trial is to assess the
      safety, efficacy and costs of remote CIED monitoring compared to traditional face
      to-face follow-up. It will evaluate aspects such as physicians' and patients'
      acceptance of and satisfaction with reviewing device data via the website, the
      complexity for troubleshooting calls to the support center, the use of emergency
      resources by symptomatic patients, the incidence of unscheduled consultations
      after remote interrogations, levels of anxiety, depression and quality of life,
      and the main resources used by the CareLink system. Approximately 200 patients
      will be randomized in up to five centers, with clinical follow-up of 12 months.
      Enrollment began in 2012 and is expected to be completed in early 2014. 

PMID- 24280080
TI  - Three different surgical approaches for transposition of the great arteries.

PMID- 24280081
TI  - Characterisation of cisplatin-induced transcriptomics responses in primary mouse
      hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of
      regulating transcription factor networks.
AB  - The toxic mechanisms of cisplatin have been frequently studied in many species
      and in vitro cell models. The Netherlands Toxicogenomics Centre focuses on
      developing in vitro alternatives using genomics technologies for animal-based
      assays on, e.g. genotoxic hazards. Models such as human hepatocellular carcinoma
      cell line (HepG2) cells, mouse primary hepatocytes (PMH) and mouse embryonic stem
      cells (mESC) are used. Our aim was to identify possibly robust conserved
      mechanisms between these models using cisplatin as model genotoxic agent.
      Transcriptomic data newly generated from HepG2 cells and PMH exposed to 7 uM
      cisplatin for 12, 24 and 48h and 24 and 48h, respectively, were compared with
      published data from mESC exposed to 5 uM cisplatin for 2-24h. Due to differences
      in response time between models and marginal changes after shorter exposure
      periods, we focused on 24 and 48h. At gene level, 44 conserved differentially
      expressed genes (DEG), involved in processes such as apoptosis, cell cycle, DNA
      damage response and DNA repair, were found. Functional analysis shows that
      limited numbers of pathways are conserved. Transcription factor (TF) network
      analysis indicates 12 common TF networks responding among all models and time
      points. Four TF, HNF4-alpha, SP1, c-MYC and p53, capable of regulating +/-50% of
      all DEG, seem of equal importance in all models and exposure periods. Here we
      showed that transcriptomic responses across several in vitro cell models
      following exposure to cisplatin are mainly determined by a conserved complex
      network of 4 TFs. These conserved responses are hypothesised to provide most
      relevant information for human toxicity prediction and may form the basis for new
      in vitro alternatives of risk assessment. 

PMID- 24280082
TI  - Membrane fouling in a submerged membrane bioreactor: effect of pH and its
      implications.
AB  - The effect of pH on membrane fouling in a submerged membrane bioreactor (MBR) was
      investigated in this study. It was found that, pH increase slightly increased the
      resistance of virgin membrane and fouled membrane. Pore clogging resistance was
      quite low, which was not apparently affected by the pH variation. Lower pH
      resulted in higher adherence of sludge flocs on membrane surface. Thermodynamic
      analysis showed that a repulsive energy barrier existed in the process of the
      foulants approaching to membrane surface. This energy barrier would decrease with
      pH decreased, suggesting the existence of a critical pH below which the repulsive
      energy barrier would disappear, which would facilitate attachment of the
      foulants. The resistance of the formed cake layer would significantly increase
      with the feed pH. This result could be explained by the osmotic pressure
      mechanism. The obtained findings also provided important implications for
      membrane fouling mitigation in MBRs. 

PMID- 24280083
TI  - The effect of quorum sensing and extracellular proteins on the microbial
      attachment of aerobic granular activated sludge.
AB  - In this study, vanillin, a quorum sensing (QS) blocker, and proteinase K were
      employed to investigate the effect of QS and extracellular proteins on the
      microbial attachment of aerobic granular activated sludge (AGAS). Results clearly
      showed that both vanillin and proteinase K could reduce attachment potential of
      AGAS, and the combined use of them was more effective in reducing attachment
      biomass of AGAS. The contents of N-acylhomoserine lactones (AHLs) and
      extracellular proteins were reduced in the presence of vanillin and proteinase K.
      Besides, it was found that extracellular proteins could promote microbial
      attachment of AGAS, and it was also revealed that AHLs-mediated QS might be
      involved in microbial attachment of AGAS through the regulation of extracellular
      proteins. This study suggested that both QS and extracellular proteins might play
      important roles in the development of "AGAS biofilm" from the perspective of the
      biofilm. 

PMID- 24280084
TI  - Mesophilic batch anaerobic co-digestion of fruit-juice industrial waste and
      municipal waste sludge: process and cost-benefit analysis.
AB  - The feasibility of anaerobic co-digestion of two juice-based beverage industrial
      wastes, screen cake (SC) and thickened waste activated sludge (TWAS), along with
      municipal sludge cake (MC) was investigated. Experiments were conducted in twenty
      mesophilic batch 160 ml serum bottles with no inhibition occurred. The
      statistical analysis proved that the substrate type had statistically significant
      effect on both ultimate biogas and methane yields (P=0.0003<0.05). The maximum
      and minimum ultimate cumulative methane yields were 890.90 and 308.34 mL/g
      VSremoved from the digesters containing only TWAS and SC as substrate. First
      order reaction model well described VS utilization in all digesters. The first 2
      day and 10-day specific biodegradation rate constants were statistically higher
      in the digesters containing SC (P=0.004<0.05) and MC (P=0.0005<0.05),
      respectively. The cost-benefit analysis showed that the capital, operating and
      total costs can be decreased by 21.5%, 29.8% and 27.6%, respectively using a co
      digester rather than two separate digesters.

PMID- 24280085
TI  - Investigation on cotton stalk and bamboo sawdust carbonization for barbecue
      charcoal preparation.
AB  - In the paper, biochar preparation from cotton stalk and bamboo sawdust by
      carbonization process was addressed. The physical and chemical properties and
      combustion characteristics of the biochar prepared using a tubular fixed bed were
      investigated. The combustion character index (S), the ignition temperature (Ti)
      and burnout temperature (Tf) were used to evaluate the combustion characteristics
      of the biochars. The results indicate that the yield and the volatile yield of
      the biochar decrease and the fixed carbon yield increases with the increase of
      the carbonization temperature. The ignition temperature and burnout temperature
      of the biochar increase and the value of S decreases when the carbonization
      temperature increases. The biochar produced from cotton stalk shows better
      combustion characteristics than the bamboo sawdust biochar does. Compared with
      commercial barbecue charcoal, the cotton stalk biochar produced under 600 
      degrees C can be utilized as barbecue charcoal.

PMID- 24280086
TI  - Effects of quinoid redox mediators on the activity of anammox biomass.
AB  - This study first explored the relationship between the activity of anammox
      biomass/key enzymes and quinoid redox mediators, which were anthraquinone-2,6
      disulfonate (AQDS), 2-hydroxy-1,4-napthoquinone (LAW) and anthraquinone-2
      carboxylic acid (AQC). Experimental results demonstrated that the total nitrogen
      removal performance showed a downward trend with all three redox mediators (RMs)
      dosage increasing. For instance, when the AQC addition increased to 0.8 mM, the
      TN removal rate sharply reduced to 17.2 mg-N/gVSS/h, only about 20% of the
      control. This phenomenon might be caused by microbial poisoning with the
      extracellular RMs additions. Nevertheless, the crude hydrazine dehydrogenase,
      nitrite reductase, and nitrate reductase activities were enhanced with RMs
      addition, about 0.6-3 folds compared to the control experiments without RMs
      addition. The RMs was inferred to play the role as ubiquinol/ubiquinone (Q/QH2)
      during the anammox process. Furthermore, the specific ladderane membrane
      structure could block the contacting between RMs and the key enzymes inside
      anammoxosome. This might be the main reason for the contrary effects of RMs on
      anammox biomass and the key enzymes.

PMID- 24280087
TI  - Distance and slope constraints: adaptation and variability in golf putting.
AB  - The main objective of this study is to understand the adaptation to external
      constraints and the effects of variability in a golf putting task. We describe
      the adaptation of relevant variables of golf putting to the distance to the hole
      and to the addition of a slope. The sample consisted of 10 adult male (33.80 +/-
      11.89 years), volunteers, right handed and highly skilled golfers with an average
      handicap of 10.82. Each player performed 30 putts at distances of 2, 3 and 4
      meters (90 trials in Condition 1). The participants also performed 90 trials, at
      the same distances, with a constraint imposed by a slope (Condition 2). The
      results indicate that the players change some parameters to adjust to the task
      constraints, namely the duration of the backswing phase, the speed of the club
      head and the acceleration at the moment of impact with the ball. The effects of
      different golf putting distances in the no-slope condition on different kinematic
      variables suggest a linear adjustment to distance variation that was not observed
      when in the slope condition. 

PMID- 24280088
TI  - High prevalence of antibiotic-resistant Mycoplasma genitalium in nongonococcal
      urethritis: the need for routine testing and the inadequacy of current treatment
      options.
AB  - BACKGROUND:  Empirical antibiotic therapy for nongonococcal urethritis (NGU) and
      cervicitis is aimed at Chlamydia trachomatis, but Mycoplasma genitalium, which
      also commonly causes undiagnosed NGU, necessitates treatment with macrolides or
      fluoroquinolones rather than doxycycline, the preferred chlamydia treatment.
      Prevalence of M. genitalium and associated genotypic markers of macrolide and
      fluoroquinolone resistance among men symptomatic of urethritis were investigated.
      Genetic diversity of M. genitalium populations was determined to infer whether
      findings were applicable beyond our setting. METHODS:  Mycoplasma genitalium and
      other NGU pathogens were detected using nucleic acid amplification methods, and
      DNA sequencing was used to detect genotypic resistance markers of macrolide and
      fluoroquinolone antibiotics in 23S ribosomal RNA, gyrA, gyrB, and parC genes.
      MG191 single-nucleotide polymorphism typing and MG309 variable number tandem
      analysis were combined to assign a dual locus sequence type (DLST) to each
      positive sample. RESULTS:  Among 217 men, M. genitalium prevalence was 16.7% (95%
      confidence interval [CI], 9.5%-24.0%) and C. trachomatis prevalence was 14.7%
      (95% CI, 7.8%-21.6%) in NGU cases. Nine of 22 (41%; 95% CI, 20%-62%) patients
      with M. genitalium were infected with DLSTs possessing genotypic macrolide
      resistance and 1 patient was infected with a DLST having genotypic
      fluoroquinolone resistance. Typing assigned M. genitalium DLSTs to 2 major
      clusters, broadly distributed among previously typed international strains.
      Genotypic macrolide resistance was spread within these 2 clusters. CONCLUSIONS: 
      Mycoplasma genitalium is a frequent undiagnosed cause of NGU in this population
      with rates of macrolide resistance higher than those previously documented.
      Current guidelines for routine testing and empirical treatment of NGU should be
      modified to reduce treatment failure of NGU and the development of further
      resistance.

PMID- 24280089
TI  - Active tuberculosis and venous thromboembolism: association according to
      international classification of diseases, ninth revision hospital discharge
      diagnosis codes.
AB  - BACKGROUND: Infections are risk factors for venous thromboembolism (VTE),
      especially if severe and acute. The role of chronic infections such as active
      tuberculosis is ill defined, although several case reports and small series have
      suggested an association between tuberculosis and VTE. METHODS: Using data from
      the Premier Perspective database (27 659 947 admissions), we performed a
      multivariate analysis to assess the specific VTE risk associated with
      tuberculosis. The analysis was adjusted on classic risk factors for VTE. RESULTS:
      The prevalence of VTE among patients with active tuberculosis was 2.07% (95%
      confidence interval [CI], 1.62%-2.59%). In a multivariate analysis model, adults
      with active tuberculosis had a greater risk of VTE than those without (odds
      ratio, 1.55 [95% CI, 1.23-1.97], P < .001), close to the previously reported risk
      associated with neoplasia. No particular link was found between pulmonary
      tuberculosis and pulmonary embolism, or between extrapulmonary tuberculosis and
      deep vein thrombosis. This may suggest the preponderant role of a systemic
      hypercoagulable state over an intrathoracic venous compression mechanism. In
      hospital mortality of patients with both active tuberculosis and VTE (11/72
      [15%]) was higher than mortality of patients with only active tuberculosis
      (92/3413 [2.7%]) or only VTE (5062/199 480 [2.5%]) (P < .001). Pulmonary embolism
      was more frequent in black patients, suggesting that this population, which is
      also more likely to suffer from tuberculosis, should be followed carefully.
      CONCLUSIONS: Tuberculosis must be considered as a pertinent risk factor for VTE
      and should be included in thromboembolism risk evaluation similar to any acute
      and severe infection.

PMID- 24280090
TI  - Effectiveness of seasonal trivalent influenza vaccine for preventing influenza
      virus illness among pregnant women: a population-based case-control study during
      the 2010-2011 and 2011-2012 influenza seasons.
AB  - BACKGROUND: Although vaccination with trivalent inactivated influenza vaccine
      (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE)
      studies of TIV in pregnant women have assessed laboratory-confirmed influenza
      outcomes. METHODS: We conducted a case-control study over 2 influenza seasons
      (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in 2
      metropolitan areas in California and Oregon. We compared the proportion
      vaccinated among 100 influenza cases (confirmed by reverse transcription
      polymerase chain reaction) with the proportions vaccinated among 192 controls
      with acute respiratory illness (ARI) who tested negative for influenza and 200
      controls without ARI (matched by season, site, and trimester). RESULTS: Among
      influenza cases, 42% were vaccinated during the study season compared to 58% and
      63% vaccinated among influenza-negative controls and matched ARI-negative
      controls, respectively. The adjusted VE of the current season vaccine against
      influenza A and B was 44% (95% confidence interval [CI], 5%-67%) using the
      influenza-negative controls and 53% (95% CI, 24%-72%) using the ARI-negative
      controls. Receipt of the prior season's vaccine, however, had an effect similar
      to receipt of the current season's vaccine. As such, vaccination in either or
      both seasons had statistically similar adjusted VE using influenza-negative
      controls (VE point estimates range = 51%-76%) and ARI-negative controls (48%
      76%). CONCLUSIONS: Influenza vaccination reduced the risk of ARI associated with
      laboratory-confirmed influenza among pregnant women by about one-half, similar to
      VE observed among all adults during these seasons.

PMID- 24280091
TI  - Considering confounders of the galactomannan index: the role of piperacillin
      tazobactam.

PMID- 24280092
TI  - Increasing trend of invasive group B streptococcal infections, Marseille, France.

PMID- 24280093
TI  - Endemic hepatitis E in the Czech Republic.
AB  - BACKGROUND: An increasing incidence of endemic hepatitis E (HE) has been reported
      in developed countries. Thus, an evaluation of the clinical characteristics of
      the disease and the utility of the current diagnostic methods is warranted.
      METHODS: Fifty-one adult acute patients with HE hospitalized in a single center
      between the years 2009 and 2012 were evaluated. Serological and molecular
      techniques (detection of hepatitis E virus [HEV] RNA from stool and serum samples
      by quantitative reverse transcription polymerase chain reaction) with sequencing
      and phylogenetic analysis were used for diagnosis, and the clinical, laboratory,
      and epidemiological parameters of the patients were evaluated. RESULTS: Forty
      nine (96.1%) patients had acute endemic HE and 2 (3.9%) had an imported
      infection. In the cohort of patients with acute symptomatic HE (n = 47), men
      outnumbered women (40:7), the patients were in older middle age (mean, 60.57
      years), and they had elevated median values of total bilirubin (6.67 mg/dL),
      alanine aminotransferase (2288.82 U/L), aspartate aminotransferase (1251.76 U/L),
      gamma-glutamyl transferase (360.53 U/L), and alkaline phosphatase (197.06 U/L).
      Serology was positive in 50 (98%) of the patients, and 1 case was diagnosed by
      polymerase chain reaction only. HEV RNA was detected in at least 1 specimen from
      84.3% of the patients, and 28 of 29 tested isolates belonged to genotype 3. The
      eating of meat, innards, other home-prepared pork products, or the tasting of raw
      meat before cooking were the most frequently reported data (reported by 25
      patients [49.0%]). CONCLUSIONS: Large numbers of the endemic cases of HE were
      caused by HEV genotype 3, and the clinical characteristics of endemic HE were
      demonstrated.

PMID- 24280094
TI  - Reply to King and Stover.

PMID- 24280095
TI  - Molecular relationships between Australian annual wild rice, Oryza meridionalis,
      and two related perennial forms.
AB  - BACKGROUND: The perennial, Oryza rufipogon distributed from Asia to Australia and
      the annual O. meridionalis indigenous to Australia are AA genome species in the
      Oryza. However, recent research has demonstrated that the Australian AA genome
      perennial populations have maternal genomes more closely related to those of O.
      meridionalis than to those found in Asian populations of O. rufipogon suggesting
      that the Australian perennials may represent a new distinct gene pool for rice.
      RESULTS: Analysis of an Oryza core collection covering AA genome species from
      Asia to Oceania revealed that some Oceania perennials had organellar genomes
      closely related to that of O meridionalis (meridionalis-type). O. rufipogon
      accessions from New Guinea carried either the meridionalis-type or rufirpogon
      type (like O. rufipogon) organellar genomes. Australian perennials carried only
      the meridionalis-type organellar genomes when accompanied by the rufipogon-type
      nuclear genome. New accessions were collected to better characterize the
      Australian perennials, and their life histories (annual or perennial) were
      confirmed by field observations. All of the material collected carried only
      meridionalis-type organellar genomes. However, there were two distinct perennial
      groups. One of them carried an rufipogon-type nuclear genome similar to the
      Australian O. rufipogon in the core collection and the other carried an
      meridionalis-type nuclear genome not represented in the existing collection.
      Morphologically the rufipogon-type shared similarity with Asian O. rufipogon. The
      meridionalis-type showed some similarities to O. meridionalis such as the short
      anthers usually characteristic of annual populations. However, the meridionalis
      type perennial was readily distinguished from O. meridionalis by the presence of
      a larger lemma and higher number of spikelets. CONCLUSION: Analysis of current
      accessions clearly indicated that there are two distinct types of Australian
      perennials. Both of them differed genetically from Asian O. rufipogon. One
      lineage is closely related to O. meridionalis and another to Asian O. rufipogon.
      The first was presumed to have evolved by divergence from O. meridionalis
      becoming differentiated as a perennial species in Australia indicating that it
      represents a new gene pool. The second, apparently derived from Asian O.
      rufipogon, possibly arrived in Australia later.

PMID- 24280096
TI  - Proteomic analysis of a disease-resistance-enhanced lesion mimic mutant spotted
      leaf 5 in rice.
AB  - BACKGROUND: A lesion-mimic mutant in rice (Oryza sativa L.), spotted leaf 5
      (spl5), displays a disease-resistance-enhanced phenotype, indicating that SPL5
      negatively regulates cell death and resistance responses. To understand the
      molecular mechanisms of SPL5 mutation-induced cell death and resistance
      responses, a proteomics-based approach was used to identify differentially
      accumulated proteins between the spl5 mutant and wild type (WT). RESULTS:
      Proteomic data from two-dimensional gel electrophoresis showed that 14 candidate
      proteins were significantly up- or down-regulated in the spl5 mutant compared
      with WT. These proteins are involved in diverse biological processes including
      pre-mRNA splicing, amino acid metabolism, photosynthesis, glycolysis, reactive
      oxygen species (ROS) metabolism, and defense responses. Two candidate proteins
      with a significant up-regulation in spl5 - APX7, a key ROS metabolism enzyme and
      Chia2a, a pathogenesis-related protein - were further analyzed by qPCR and enzyme
      activity assays. Consistent with the proteomic results, both transcript levels
      and enzyme activities of APX7 and Chia2a were significantly induced during the
      course of lesion formation in spl5 leaves. CONCLUSIONS: Many functional proteins
      involving various metabolisms were likely to be responsible for the lesion
      formation of spl5 mutant. Generally, in spl5, the up-regulated proteins involve
      in defense response or PCD, and the down-regulated ones involve in amino acid
      metabolism and photosynthesis. These results may help to gain new insight into
      the molecular mechanism underlying spl5-induced cell death and disease resistance
      in plants.

PMID- 24280097
TI  - An amelanotic dysplastic melanocytic nevus induced by vemurafenib.

PMID- 24280098
TI  - Endoscopic transsphenoidal drainage of an aggressive petrous apex cholesterol
      granuloma: unusual complications and lessons learnt.
AB  - OBJECTIVES: This case report describes the endoscopic transsphenoidal management
      of a cholesterol granuloma situated in a technically challenging part of the
      petrous apex, and the associated peri- and post-operative complications that
      arose. The literature on diagnosis and management of petrous apex cholesterol
      granulomas is reviewed. METHOD AND RESULTS: Surgical intervention was attempted
      on three occasions, each time via an endoscopic, transsphenoidal approach with
      image guidance. The procedure was abandoned on the first occasion as there was a
      significant risk to the carotid artery; only a small drainage ostium was created
      because of the proximity of the carotid artery. The second attempt, complicated
      by copious bleeding from the clival venous plexus, was arrested prematurely.
      Successful drainage was achieved at the third attempt, but recovery was
      complicated by tension pneumocephalus. CONCLUSION: The transnasal route is less
      invasive than a lateral labyrinthine or cochlear approach, and spares cochlear
      and vestibular function. However, this approach is not without risk. It is
      important to consider the natural anatomical variance of vasculature when
      planning surgical intervention for a lesion situated in a technically challenging
      part of the petrous apex. Additional magnetic resonance venography is recommended
      to circumnavigate the venous plexus, thereby avoiding an unexpected breach.

PMID- 24280099
TI  - Effects of inorganic or organic selenium on immunoglobulins in swine.
AB  - A study was conducted to determine if Se source fed during gestation and
      lactation affects passive transfer of immunoglobulins. Sixty days prior to
      breeding (d -60), gilts were randomly assigned to one of three treatments prior
      to breeding and throughout gestation: control (Control, no supplemental Se; n =
      8), inorganic Se (Inorganic Se, 0.3 ppm; n = 4) and organic Se (Organic Se, 0.3
      ppm; n = 4). Blood was collected on d -60, 57 and 113 of gestation and on d 21 of
      lactation and milk was collected at d 0, 1, 7, 14, and 21 of lactation. Blood was
      collected from piglets at d 0, 1, 7, 14, and 21 of age. Gilts fed organic Se had
      greater (P < 0.05) circulating concentrations of Se than Inorganic and Control
      gilts. Regardless of treatment, circulating concentrations of Se were greatest (P
      < 0.05) at d -60 compared to all other days. Serum concentrations of IgG were
      greatest (P < 0.05) in gilts at d 57 of gestation compared to d 113. Serum
      concentrations of IgA were greatest (P < 0.05) on d 113 of gestation and d 21 of
      lactation compared to d -60 and 57. Serum concentrations of IgM were greater (P <
      0.05) at d 57 compared to d -60. Inorganic gilts had greater (P < 0.05) colostral
      and milk concentrations of IgG and IgM than Organic or Control gilts. Circulating
      concentrations of Se in piglets were greatest (P < 0.05) at d 14 and 21 of age
      compared to all other days. Piglets from gilts supplemented with organic Se had
      greater (P < 0.05) circulating concentrations of Se on d 1 versus piglets from
      gilts supplemented with no additional Se. The immunoglobulin concentrations of
      IgG, IgA, and IgM were lowest (P < 0.05) on d 0 and then increased when compared
      to d 1. The addition of different sources of Se did not affect the immunoglobulin
      concentrations in the gilt or piglet. 

PMID- 24280100
TI  - Novel role for carbamoyl phosphate synthetase 2 in cranial sensory circuit
      formation.
AB  - In zebrafish, cranial sensory circuits form by 4 days post-fertilization. We used
      a forward genetic screen to identify genes involved in the formation of these
      circuits. In one mutant allele, sl23, axons arising from the epibranchial sensory
      ganglia do not form their stereotypical terminal fields in the hindbrain. These
      embryos also had small eyes and deformed jaws, suggesting a pleiotropic effect.
      Using positional cloning, a 20-nucleotide deletion in the carbamoyl-phosphate
      synthetase2-aspartate-transcarbamylase-dihydroorotase (cad) gene was found.
      Injection of a CAD morpholino phenocopied the mutant and mutants were rescued by
      injection of cad RNA. Cad activity is required for pyrimidine biosynthesis, and
      thus is a prerequisite for nucleic acid production and UDP-dependent protein
      glycosylation. Perturbation of nucleic acid biosynthesis can result in cell
      death. sl23 mutants did not exhibit elevated cell death, or gross morphological
      changes, in their hindbrains. To determine if defective protein glycosylation was
      involved in the aberrant targeting of sensory axons, we treated wild type embryos
      with tunicamycin, which blocks N-linked protein glycosylation. Interference with
      glycosylation via tunicamycin treatment mimicked the sl23 phenotype. Loss of cad
      reveals a critical role for protein glycosylation in cranial sensory circuit
      formation. 

PMID- 24280102
TI  - Response to the letter to the editor "the use of oral nutritional supplements in
      patients with head and neck cancer receiving (chemo)radiotherapy".

PMID- 24280101
TI  - High homocysteine is associated with increased risk of colorectal cancer
      independently of oxidative stress and antioxidant capacities.
AB  - BACKGROUND & AIMS: Increased homocysteine concentration and oxidative stress and
      decreased antioxidant capacities are thought to affect carcinogenesis. However,
      the associations of homocysteine, cysteine, pyridoxal 5'-phosphate (PLP) and
      folate with oxidative stress and antioxidant capacities in patients with
      colorectal cancer are unclear. The purpose of this study was to determine the
      associations of homocysteine, cysteine, PLP and folate with oxidative stress
      indicators and antioxidant capacities, and to further analyze their relationships
      with respect to risk for colorectal cancer. METHODS: One hundred and sixty-eight
      subjects with colorectal cancer (cases) and 188 healthy subjects (controls) were
      recruited. RESULTS: There were no significant associations of homocysteine,
      cysteine and folate with oxidative stress indicators and antioxidant capacities
      in cases; however, PLP positively correlated with glutathione S-transferase
      activities after adjusting for potential confounders in cases. Subjects with
      higher plasma homocysteine concentration exhibited significantly increased risk
      of colorectal cancer with or without adjustment for potential confounders. The
      associations of cysteine, PLP and folate with the risk of colorectal cancer were
      not observed when potential confounders were adjusted. CONCLUSIONS: Increased
      homocysteine was strongly associated with the risk of colorectal cancer
      independently of oxidative stress indicators and antioxidant capacities. However,
      cysteine, PLP and folate were not found to be related to oxidative stress,
      antioxidant capacities and the risk of colorectal cancer.

PMID- 24280103
TI  - A tensor-based scheme for stroke patients' motor imagery EEG analysis in BCI-FES
      rehabilitation training.
AB  - BACKGROUND: Stroke is one of the most common disorders among the elderly. A
      practical problem in stroke rehabilitation systems is that how to separate motor
      imagery patterns from electroencephalographic (EEG) recordings. There is a sharp
      decline in performance of these systems when classical algorithms, such as Common
      Spatial Pattern (CSP), are directly applied on stroke patients. NEW METHOD: We
      propose a tensor-based scheme to detect motor imagery EEG patterns in spatial
      spectral-temporal domain directly from multidimensional EEG constructed by
      wavelet transform method. Discriminative motor imagery EEG patterns are obtained
      by Fisher score strategy. Furthermore, the most contributed channel groups and
      frequency bands are selected from these patterns and utilized as prior knowledge
      for the following motor imagery tasks. RESULTS: We evaluate our scheme based on
      EEG datasets recorded from stroke patients. The results show that our method
      outperforms five other traditional methods in both online and offline recognition
      performance. COMPARISON WITH EXISTING METHODS: Unlike the existing methods, motor
      imagery EEG patterns in spatial-spectral-temporal domain are simultaneously
      obtained by our method, preserving the structural information of the multi
      channel time-varying EEG. CONCLUSIONS: Our scheme is encouraged to be transferred
      to some other practical rehabilitation applications for its better performance.

PMID- 24280104
TI  - Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on
      bronchodilator response in asthmatics.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) influence a patient's response
      to inhaled corticosteroids and beta2-agonists, and the effect of treatment with
      inhaled corticosteroids is synergistic with the effect of beta2-agonists. We
      hypothesized that use of inhaled corticosteroids could influence the effect of
      SNPs associated with a bronchodilator response. OBJECTIVE: To assess whether,
      among subjects with asthma, the association of SNPs with bronchodilator response
      is different between those treated with inhaled corticosteroids versus those on
      placebo. METHODS: A genome-wide association analysis was conducted by using 581
      white subjects from the Childhood Asthma Management Program. By using data for
      449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled
      corticosteroid treatment as the environmental exposure and bronchodilator
      response as the outcome measure. We attempted to replicate the top 12 SNPs in the
      Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial.
      RESULTS: The combined P value for the Childhood Asthma Management Program and
      Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial
      populations was 4.8 * 10(-8) for rs3752120, which is located in the zinc finger
      protein gene ZNF432 and has an unknown function. CONCLUSIONS: Inhaled
      corticosteroids appear to modulate the association of bronchodilator response
      with variant(s) in the ZNF432 gene among adults and children with asthma.

PMID- 24280105
TI  - Patients offered orthognathic surgery: why do many refrain from treatment?
AB  - AIM: To examine factors associated with patients' decision to decline surgery.
      MATERIAL/METHODS: Of 470 consecutive patients referred to the University of Oslo
      from 2007 to 2009, a sample of 160 subjects who had not undergone surgery was
      identified and contacted. 236 operated patients from the same period served as a
      comparison group. Morphology was assessed from cephalograms and photographs, and
      the individuals' opinions were recorded using questionnaires. RESULTS:
      Dentofacial morphology represented normative treatment need and was generally
      similar except for a higher rate of severe negative overjet in the operated group
      (p < 0.001). The most prevalent reasons for declining surgery were risks of side
      effects, the burden of care, and a general reluctance to undergo surgery. Many un
      operated subjects were dissatisfied with their masticatory function and
      dentofacial appearance. CONCLUSION: Informed consent to orthognathic surgery
      represents a challenge both to the patient and the professional. The findings
      imply that patients' motives and fears should be explored during consultation and
      that the information provided should be adapted to the potential risks and
      benefits related to the actual treatment.

PMID- 24280106
TI  - Ameloblastoma with varied sites of metastasis: report of two cases and literature
      review.
AB  - OBJECTIVE: We report two rare cases of lung metastasis from maxillary
      ameloblastoma, in order to review its risk and analyse the types of metastases
      that can present with this disease. METHODS: A 40-year-old male with multiple
      recurrences and a 46-year-old female, who had undergone successful surgical
      treatment of a maxillary ameloblastoma, presented with metastatic lesions. The
      primary tumour and metastases were benign in both patients. We reviewed and
      analysed 20 cases of the same condition reported in recent years. RESULTS: Our
      initial treatment for the primary maxillary lesion was performed more than 10
      years before the pulmonary lesions presented. Due to the aggressive nature of
      this tumour, metastases in the lungs and cervical lymph nodes (male patient) were
      confirmed. CONCLUSION: These cases presented a diagnostic challenge due to the
      multiple and varied sites of recurrence, which indicate the natural behaviour of
      this tumour. Different routes of metastasis can occur, including implanting,
      haematogenous, and lymphatic spread. CT-guided percutaneous transthoracic lung
      biopsy is an important method to confirm metastatic ameloblastoma.

PMID- 24280107
TI  - Why Cancer & Metabolism? Why now?

PMID- 24280108
TI  - Metabolic changes in cancer cells upon suppression of MYC.
AB  - BACKGROUND: Cancer cells engage in aerobic glycolysis and glutaminolysis to
      fulfill their biosynthetic and energetic demands in part by activating MYC.
      Previous reports have characterized metabolic changes in proliferating cells upon
      MYC loss or gain of function. However, metabolic differences between MYC
      dependent cancer cells and their isogenic differentiated counterparts have not
      been characterized upon MYC suppression in vitro. RESULTS: Here we report
      metabolic changes between MYC-dependent mouse osteogenic sarcomas and
      differentiated osteoid cells induced upon MYC suppression. While osteogenic
      sarcoma cells increased oxygen consumption and spare respiratory capacity upon
      MYC suppression, they displayed minimal changes in glucose and glutamine
      consumption as well as their respective contribution to the citrate pool.
      However, glutamine significantly induced oxygen consumption in the presence of
      MYC which was dependent on aminotransferases. Furthermore, inhibition of
      aminotransferases selectively diminished cell proliferation and survival of
      osteogenic sarcoma MYC-expressing cells. There were minimal changes in ROS levels
      and cell death sensitivity to reactive oxygen species (ROS)-inducing agents
      between osteoid cells and osteogenic sarcoma cells. Nevertheless, the
      mitochondrial-targeted antioxidant Mito-Vitamin E still diminished proliferation
      of MYC-dependent osteogenic sarcoma cells. CONCLUSION: These data highlight that
      aminotransferases and mitochondrial ROS might be attractive targets for cancer
      therapy in MYC-driven tumors.

PMID- 24280109
TI  - AINTEGUMENTA-LIKE proteins: hubs in a plethora of networks.
AB  - Members of the AINTEGUMENTA-LIKE (AIL) family of APETALA 2/ETHYLENE RESPONSE
      FACTOR (AP2/ERF) domain transcription factors are expressed in all dividing
      tissues in the plant, where they have central roles in developmental processes
      such as embryogenesis, stem cell niche specification, meristem maintenance, organ
      positioning, and growth. When overexpressed, AIL proteins induce adventitious
      growth, including somatic embryogenesis and ectopic organ formation. The
      Arabidopsis (Arabidopsis thaliana) genome contains eight AIL genes, including
      AINTEGUMENTA, BABY BOOM, and the PLETHORA genes. Studies on these transcription
      factors have revealed their intricate relationship with auxin as well as their
      involvement in an increasing number of gene regulatory networks, in which
      extensive crosstalk and feedback loops have a major role. 

PMID- 24280110
TI  - NSAID use and association with cardiovascular outcomes in outpatients with stable
      atherothrombotic disease.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin have
      been linked to heart failure, salt retention, adverse ventricular remodeling, and
      thrombosis. We therefore sought to assess their impact on cardiovascular events
      in outpatients with stable atherothrombotic disease. METHODS: We analyzed 44,095
      patients in the REduction of Atherothrombosis for Continued Health (REACH)
      registry with information on NSAID use and 4-year follow-up. Cox proportional
      hazard models, including NSAID use as a time-dependent covariate, were
      constructed and adjusted for key baseline characteristics. End points of interest
      included multivariate adjusted: cardiovascular death/myocardial
      infarction/stroke/ischemic hospitalizations; cardiovascular death/myocardial
      infarction/stroke; hospitalization for heart failure; and individual components
      of the composite end points. RESULTS: Compared with NSAID nonusers (n = 39,675),
      NSAID users (n = 4420) were older (70 vs 68 years), more frequently female and
      white, and had more baseline heart failure and atherosclerotic risk factors
      (hypertension, dyslipidemia, diabetes, reduced creatinine clearance) (all P <
      .001). NSAID use was associated with an increased hazard for cardiovascular
      death/myocardial infarction/stroke/ischemic hospitalizations (adjusted hazard
      ratio [adj. HR] 1.12; 95% confidence interval [CI], 1.04-1.21; P = .003) and for
      cardiovascular death/myocardial infarction/stroke (adj. HR 1.16; 95% CI, 1.03
      1.30; P = .02). There also was a higher risk of myocardial infarction (adj. HR
      1.37; 95% CI, 1.12-1.68; P = .002), stroke (adj. HR 1.21; 95% CI, 1.00-1.45; P =
      .048), heart failure hospitalizations (adj. HR 1.18; 95% CI, 1.03-1.34; P =
      .013), and ischemic hospitalizations (adj. HR 1.17; 95% CI, 1.07-1.27; P = .001).
      CONCLUSION: Among patients with stable atherothrombosis, NSAID use is associated
      with a higher risk of myocardial infarction, stroke, and hospitalizations for
      both ischemia and heart failure.

PMID- 24280111
TI  - Decision-support information system to manage mass casualty incidents at a level
      1 trauma center.
AB  - Mass casualty incidents are probably the greatest challenge to a hospital. When
      such an event occurs, hospitals are required to instantly switch from their
      routine activity to conditions of great uncertainty and confront needs that
      exceed resources. We describe an information system that was uniquely designed
      for managing mass casualty events. The web-based system is activated when a mass
      casualty event is declared; it displays relevant operating procedures,
      checklists, and a log book. The system automatically or semiautomatically
      initiates phone calls and public address announcements. It collects real-time
      data from computerized clinical and administrative systems in the hospital, and
      presents them to the managing team in a clear graphic display. It also generates
      periodic reports and summaries of available or scarce resources that are sent to
      predefined recipients. When the system was tested in a nationwide exercise, it
      proved to be an invaluable tool for informed decision making in demanding and
      overwhelming situations such as mass casualty events.

PMID- 24280113
TI  - Role of subtotal tonsillectomy ('tonsillotomy') in children with sleep disordered
      breathing.
AB  - INTRODUCTION: Sleep disordered breathing in children causes disturbance in
      behaviour and also in cardiorespiratory and neurocognitive function. Subtotal
      tonsillectomy ('tonsillotomy') has been performed to treat sleep disordered
      breathing, with outcomes comparable to established therapies such as total
      tonsillectomy or adenoidectomy. This review critically assesses the role of
      subtotal tonsillectomy in a paediatric setting. METHOD: The Medline database
      (1966 to October 2012) was electronically searched using key terms including
      subtotal or intracapsular tonsillectomy, tonsillotomy, tonsillectomy,
      paediatrics, and sleep disordered breathing. RESULTS: Eighteen papers were
      identified and reviewed. Subtotal tonsillectomy would appear to have an efficacy
      equal to that of total tonsillectomy for the treatment of sleep disordered
      breathing, and has significant benefits in reducing post-operative pain and
      analgesia use. Subtotal tonsillectomy patients appear to have less frequent post
      operative haemorrhage compared with total tonsillectomy patients. CONCLUSION: In
      children, subtotal tonsillectomy is associated with fewer post-operative
      complications whilst having a comparable effect in improving sleep disordered
      breathing, compared with total tonsillectomy.

PMID- 24280112
TI  - Insights into genomics of salt stress response in rice.
AB  - Plants, as sessile organisms experience various abiotic stresses, which pose
      serious threat to crop production. Plants adapt to environmental stress by
      modulating their growth and development along with the various physiological and
      biochemical changes. This phenotypic plasticity is driven by the activation of
      specific genes encoding signal transduction, transcriptional regulation, ion
      transporters and metabolic pathways. Rice is an important staple food crop of
      nearly half of the world population and is well known to be a salt sensitive
      crop. The completion and enhanced annotations of rice genome sequence has
      provided the opportunity to study functional genomics of rice. Functional
      genomics aids in understanding the molecular and physiological basis to improve
      the salinity tolerance for sustainable rice production. Salt tolerant transgenic
      rice plants have been produced by incorporating various genes into rice. In this
      review we present the findings and investigations in the field of rice functional
      genomics that includes supporting genes and networks (ABA dependent and
      independent), osmoprotectants (proline, glycine betaine, trehalose, myo-inositol,
      and fructans), signaling molecules (Ca2+, abscisic acid, jasmonic acid,
      brassinosteroids) and transporters, regulating salt stress response in rice. 

PMID- 24280115
TI  - Predictors of complication for alveolar cleft bone graft.
AB  - We have analysed the predictors of postoperative complications and the need for
      reoperation after grafting of the alveolar cleft from one specialised cleft
      centre. The data were obtained from hospital casenotes of patients operated on
      from December 2004 to April 2010, with a minimum one-year follow-up from the
      final operation. Independent variables included postoperative complications and
      the need for reoperation. Conditional variables were sex, age, type of cleft,
      sides affected, donor area, type of graft material, and the presence of an
      erupted tooth in contact with the cleft. A total of 71 patients had bone grafted
      on to the alveolar cleft. The following associations were found to be
      significant: postoperative complications and need for reoperation (p=0.003); age
      and complications (p=0.002); affected side and complications (p=0.006); age and
      reoperation (p=0.000); sex and reoperation (p=0.001); and type of cleft and
      reoperation (p=0.001). Proper attention should be given to all the variables and
      risk factors to overcome the many obstacles that might have an adverse influence
      on a successful outcome of alveolar bone grafting for patients with clefts. 

PMID- 24280116
TI  - Analysis of time taken to discuss new patients with head and neck cancer in
      multidisciplinary team meetings.
AB  - Multidisciplinary team (MDT) meetings have an important role in the management of
      head and neck cancer. Increasing incidence of the disease and a drive towards
      centralised meetings on large numbers of patients mean that effective discussions
      are pertinent. We aimed to evaluate new cases within a single high volume head
      and neck cancer MDT and to explore the relation between the time taken to discuss
      each case, the number of discussants, and type of case. A total of 105 patients
      with a new diagnosis of head and neck malignancy or complex benign tumour were
      discussed at 10 head and neck cancer MDT meetings. A single observer timed each
      discussion using a stopwatch, and recorded the number of discussants and the
      diagnosis and characteristics of each patient. Timings ranged from 15 to 480 s (8
      min) with a mean of 119 s (2 min), and the duration of discussion correlated
      closely with the number of discussants (rs=0.63, p<0.001). The longest
      discussions concerned patients with advanced T stage (p=0.006) and advanced N
      stage (p=0.009) disease, the elderly (p=0.02) and male patients (p=0.05). Tumour
      site and histological findings were not significant factors in the duration of
      discussion. Most discussions on patients with early stage tumours were short (T1:
      58% less than 60s, mean 90) and fewer people contributed. Many patients,
      particularly those with early stage disease, require little discussion, and their
      treatment might reasonably be planned according to an agreed protocol, which
      would leave more time and resources for those that require greater
      multidisciplinary input. Further studies may highlight extended discussions on
      patients with head and neck cancer, which may prompt a review of protocols and
      current evidence.

PMID- 24280117
TI  - Assessment of quality of life and sociocultural aspects in patients with
      ameloblastoma after immediate mandibular reconstruction with a fibular free flap.
AB  - Our aim was to evaluate the quality of life (QoL) in patients with ameloblastoma
      who had been treated by immediate mandibular reconstruction with a fibular free
      flap, and to analyse the association between QoL and their sociocultural and
      medical characteristics. We assessed the QoL outcomes of 33/45 patients using the
      University of Washington quality of life (UW-QoL) questionnaire and the 14-item
      Oral Health Impact Profile (OHIP-14). Thirty-three of the 45 questionnaires were
      returned (73%). In the UW-QoL the best-scoring domain was "shoulder", whereas the
      lowest scores were for "chewing" and "activity". In the OHIP-14 the lowest
      scoring domain was "handicap", followed by "social disability" and "psychological
      discomfort". Mandibular reconstruction with a fibular free flap significantly
      influenced the patients' QoL and oral function. Their sociocultural data showed
      that most patients had a fairly low level of education. 

PMID- 24280118
TI  - Sialoendoscopy with and without holmium:YAG laser-assisted lithotripsy in the
      management of obstructive sialadenitis of major salivary glands.
AB  - Obstructive sialadenitis is a major cause of dysfunction of the salivary glands,
      and increasingly sialoendoscopy is used in both diagnosis and treatment. At
      present the limit of the endoscopic approach is the size of the stone as only
      stones of less than 4mm can be removed. Endoscopic laser lithotripsy has the
      potential to treat many stones larger than this with minimal complications and
      preservation of a functional salivary gland. The holmium:YAG laser has been
      widely and safely used in urology, and its use has been recently proposed in
      salivary lithotripsy for the removal of bigger stones. We describe our experience
      with sialoendoscopy for stones in the parotid and submandibular glands and assess
      the feasibility and the efficacy of holmium:YAG laser lithotripsy. We have used
      the procedure 50 times for 43 patients with obstructive sialadenitis; 31 patients
      had sialolithiasis, 15 of whom (48%) had stones with diameters between 4 and 15mm
      (mean 7). Total extraction after fragmentation was possible in 14 of the 15
      patients without complications. Intraductal holmium:YAG laser lithotripsy is
      effective and safe, and allows the treatment of large stones in Stensen's and
      Wharton's ducts.

PMID- 24280119
TI  - Understanding the relationship between schizotypy and attention: dissociating
      stimulus- and dimension-specific processes.
AB  - Two experiments investigated how the schizotypal characteristics of unusual
      experiences modulate changes in attention to alphanumeric stimuli. In the first
      stage of both experiments, participants were required to attend and respond to
      either Arabic numerals or Latin letters; with the four exemplars from each
      dimension being presented on a different number of occasions (0, 5, 10, 20).
      During the test in Experiment 1 (n=103), speeded alphanumeric decisions were more
      accurate for the novel than familiar exemplars, irrespective of whether they had
      been attended to or not. This influence of familiarity was not modulated by
      schizotypy. During the test in Experiment 2 (n=128), learning that the attended
      dimension predicted the presentation of the symbol X (or the absence of X)
      proceeded more rapidly than learning the corresponding predictions involving the
      unattended dimension. In the case of novel exemplars, but not familiar exemplars,
      this modulation of learning by attention was reduced as schizotypy scores
      increased. Taken together, these results show that schizotypal characteristics do
      not modulate the influence of familiarity on performance (Experiment 1), but do
      have an influence on attention, which is best characterised as one on tuning
      attention to stimulus dimensions rather than individual stimuli. 

PMID- 24280120
TI  - Subtle gait abnormalities in Nedd4 heterozygous mice.
AB  - Nedd4 is a widely expressed ubiquitin ligase that is necessary for normal
      neuronal development and function. However, largely due to the lethality of Nedd4
      homozygous knockout mice, little is known about the physiological roles of Nedd4
      in the adult brain. In this study we used Nedd4 heterozygous mice, which are
      viable and live to maturity, to assess for motor function and gait. Global motor
      function was not altered in these mice, a result consistent with the low level of
      Nedd4 expression observed in motor neurons of the spinal cord. However, Nedd4
      heterozygous mice showed significant age-dependent changes in gait. The gait
      abnormalities included an overall extension of gait that was only evident in the
      6 month old mice. We also observed distinct expression patterns of Nedd4, with
      pronounced staining in the Purkinje neurons of the cerebellum that are crucial
      for normal gait, and lower levels in other motor areas of the CNS. It has been
      recently shown that Nedd4 directly interacts with GluR1 containing AMPA receptors
      in an activity dependent manner to modulate receptor levels at the post-synaptic
      membrane. Using confocal immunohistochemistry, we found that there were subtle
      changes in GluR1 expression in 6 month old Nedd4 heterozygous mice. There
      appeared to be a redistribution of GluR1 into larger puncta in the molecular
      layer and in the membrane of the soma of the Purkinje neurons. This study is the
      first to show that a 50% reduction in Nedd4 levels is sufficient to produce
      significant gait defects in 6 month old mice. These defects may arise in part,
      from altered distribution of GluR1 in cerebellar neurons. 

PMID- 24280121
TI  - Time-of-day effect on a food-induced conditioned place preference task in
      monkeys.
AB  - Time can be an important contextual cue for cognitive performance, with
      implications for reward-associated learned behaviors such as (drug and food)
      addiction. So, we analyzed: (1) if marmoset monkeys develop a place preference
      that is conditioned to previous pairings with a highly-palatable food reward; (2)
      if the response is strongest when training and testing times match - time stamp
      effect; and (3) if there is an optimal time of the day (morning vs. afternoon)
      when this preference occurs - time-of-day effect. Subjects were first habituated
      to a two-compartment conditioned-place-preference (CPP) box. Then, during six
      training sessions held either in the morning or afternoon, a mixture of
      jellybeans and live mealworms was made available in a specific compartment.
      Marmosets were subsequently tested for preferring the food-paired context at the
      circadian time that either matched or was different from that of training.
      Compared to baseline levels, only subjects trained and tested in the afternoon
      made significantly longer and more frequent visits to the food-paired context and
      with a shorter latency to first entry. Thus, highly-palatable food rewards
      induced a CPP response. This behavior was exhibited only when training and
      testing times overlapped and during a restricted circadian timeframe (afternoon),
      consistent with a time-stamp and time-of-day effect, respectively. In this case,
      time may have been an internal circadian contextual cue. Whether due to circadian
      mediated oscillations in memory and/or reward processes, such findings may be
      applied to addiction and other learned behaviors. 

PMID- 24280122
TI  - The P-glycoprotein inhibitor cyclosporin A differentially influences behavioural
      and neurochemical responses to the antidepressant escitalopram.
AB  - Recent studies have raised the possibility that P-glycoprotein (P-gp) inhibition
      may represent a putative augmentation strategy for treatment with certain
      antidepressants. Indeed, we have previously shown that administration of the P-gp
      inhibitor verapamil increased the brain distribution and behavioural effects of
      the antidepressant escitalopram. The aim of the current study was to investigate
      if similar effects occur with another P-gp inhibitor, cyclosporin A (CsA). CsA
      pre-treatment exacerbated the severity of behaviours in an escitalopram-induced
      mouse model of serotonin syndrome, a potentially life-threatening adverse drug
      reaction associated with serotonergic drugs. P-gp inhibition by CsA enhanced the
      brain distribution of escitalopram by 70-80%. Serotonin (5-HT) turnover in the
      prefrontal cortex was reduced by escitalopram, and this effect was augmented by
      CsA. However, CsA pre-treatment did not augment the effect of escitalopram in the
      tail suspension test (TST) of antidepressant-like activity. Microdialysis
      experiments revealed that pre-treatment with CsA failed to augment, but blunted,
      the increase in extracellular 5-HT in response to escitalopram administration.
      This blunting effect may contribute to the lack of augmentation in the TST. Taken
      together, the present studies demonstrate that co-administration of CsA and
      escitalopram produces differential effects depending on the behavioural and
      neurochemical assays employed. Thus, the results highlight the need for further
      studies involving more selective pharmacological tools to specifically evaluate
      the impact of P-gp inhibition on behavioural responses to antidepressants which
      are subject to efflux by P-gp. 

PMID- 24280123
TI  - Nonstationarity of stable States in rhythmic bimanual coordination.
AB  - The HKB model and its variants characterize bimanual coordination with fixedpoint
      dynamics and predict stationarity of the mean and variance of relative phase in
      stable coordinative states. In the current study, participants performed in-phase
      and antiphase coordination modes in rhythmic bimanual finger and elbow
      flexionextension tasks. The results of runs tests revealed that discrete relative
      phase was nonstationary in 49.25%, 50.25%, and 54% of time-series in the 10, 20,
      and 30 box runs tests, respectively. In all individual Task conditions >38% of
      time-series were nonstationary. These findings contradicted model predictions
      that the mean and variance of relative phase are stationary in bimanual
      coordination and distinguish the concept of dynamical stability from statistical
      stationarity. The findings indicated that relative phase was not attracted to a
      stationary fixed-point and that fluctuations in relative phase are not Gaussian
      white noise as in existing models of bimanual coordination. 

PMID- 24280124
TI  - Attenuation of adjuvant-induced arthritis in rats by phonophoresis with an
      aqueous gel of the Amazonian plant Elaeoluma nuda (Sapotaceae).
AB  - BACKGROUND: Various species of the genus Pouteria (Elaeoluma) are used by the
      native population of Brazil because of, among other factors, their anti
      inflammatory properties. The anti-inflammatory properties of the extract of the
      Amazonian plant Elaeoluma nuda were recently identified in prospective
      pharmacological studies. OBJECTIVES: The objective of this study was to assess
      the anti-inflammatory effect of phonophoresis with aqueous gel extract of E. nuda
      in rat adjuvant-induced arthritis. METHODOLOGY: Arthritis was induced in Lewis
      rats with an adjuvant. Phonophoresis with E. nuda gel was then administered daily
      and the results compared with those obtained with phonophoresis of diclofenac
      diethylammonium gel and ultrasound therapy without phonophoresis. Arthritis in
      the different groups was evaluated by plethysmometry. Proinflammatory cytokines
      TNF-alpha and IL-1alpha were quantified by cytometric bead array (CBA). RESULTS:
      The effect of phonophoresis of aqueous gel with E. nuda extract on arthritis in
      rats' paws (a 33% reduction compared with the controls) was the same as that
      produced by phonophoresis with diclofenac diethylammonium. Ultrasound therapy
      without phonophoresis produced no significant effect on the 21st day of therapy.
      There was a significant reduction in TNF-alpha and IL-1alpha levels in the group
      treated with phonophoresis with E. nuda gel (p=0.0042; p=0.0003, respectively).
      CONCLUSION: Our results demonstrate the anti-inflammatory effect of phonophoresis
      with E. nuda gel on cytokines TNF-alpha, IL-1alpha and adjuvant-induced
      arthritis.

PMID- 24280125
TI  - Dorsomorphin reverses the mesenchymal phenotype of breast cancer initiating cells
      by inhibition of bone morphogenetic protein signaling.
AB  - Increasing evidence supports the theory that tumor growth, homeostasis, and
      recurrence are dependent on a small subset of cells with stem cell properties,
      redefined cancer initiating cells (CICs) or cancer stem cells. Bone morphogenetic
      proteins (BMPs) are involved in cell-fate specification during embryogenesis, in
      the maintenance of developmental potency in adult stem cells and may contribute
      to sustain CIC populations in breast carcinoma. Using the mouse A17 cell model
      previously related to mesenchymal cancer stem cells and displaying properties of
      CICs, we investigated the role of BMPs in the control of breast cancer cell
      plasticity. We showed that an autocrine activation of BMP signaling is crucial
      for the maintenance of mesenchymal stem cell phenotype and tumorigenic potential
      of A17 cells. Pharmacological inhibition of BMP signaling cascade by Dorsomorphin
      resulted in the acquisition of epithelial-like traits by A17 cells, including
      expression of Citokeratin-18 and E-cadherin, through downregulation of Snail and
      Slug transcriptional factors and Cyclooxygenase-2 (COX2) expression, and in the
      loss of their stem-features and self-renewal ability. This phenotypic switch
      compromised A17 cell motility, invasiveness and in vitro tumor growth. These
      results reveal that BMPs are key molecules at the crossroad between stemness and
      cancer. 

PMID- 24280127
TI  - Pharmacological enhancement of leg and muscle microvascular blood flow does not
      augment anabolic responses in skeletal muscle of young men under fed conditions.
AB  - Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and
      insulinemia is contingent upon amino acids (AA) and insulin crossing the
      microcirculation-myocyte interface. In this study, we hypothesized that
      increasing muscle microvascular blood volume (flow) would enhance fed-state
      anabolic responses in muscle protein turnover. We studied 10 young men (23.2 +/-
      2.1 yr) under postabsorptive and fed [iv Glamin (~10 g AA), glucose ~7.5 mmol/l]
      conditions. Methacholine was infused into the femoral artery of one leg to
      determine, via bilateral comparison, the effects of feeding alone vs. feeding
      plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral
      artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by
      contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown
      (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2
      (13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass
      spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g.,
      Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed
      conditions, LBF (+12 +/- 5%, P < 0.05), MBV (+25 +/- 10%, P < 0.05), and MPS
      (+129 +/- 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF
      (+126 +/- 12%, P < 0.05) and MBV (+79 +/- 30%, P < 0.05). Despite these radically
      different blood flow conditions, neither increases in MPS in response to feeding
      (0.04 +/- 0.004 vs. 0.08 +/- 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 +/-
      2.4 vs. 16.4 +/- 5.7 nmol Phe.100 ml leg(-1).min(-1), P < 0.05) were affected by
      methacholine infusion (MPS 0.07 +/- 0.01%/h; NPB 24.0 +/- 7.7 nmol Phe.100 ml
      leg(-1).min(-1)), whereas MPB was unaltered by either feeding or infusion of
      methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding
      alone does not improve muscle anabolism. 

PMID- 24280126
TI  - Loss of Pgc-1alpha expression in aging mouse muscle potentiates glucose
      intolerance and systemic inflammation.
AB  - Diabetes risk increases significantly with age and correlates with lower
      oxidative capacity in muscle. Decreased expression of peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (Pgc-1alpha) and target gene pathways
      involved in mitochondrial oxidative phosphorylation are associated with muscle
      insulin resistance, but a causative role has not been established. We sought to
      determine whether a decline in Pgc-1alpha and oxidative gene expression occurs
      during aging and potentiates the development of age-associated insulin
      resistance. Muscle-specific Pgc-1alpha knockout (MKO) mice and wild-type
      littermate controls were aged for 2 yr. Genetic signatures of skeletal muscle
      (microarray and mRNA expression) and metabolic profiles (glucose homeostasis,
      mitochondrial metabolism, body composition, lipids, and indirect calorimetry) of
      mice were compared at 3, 12, and 24 mo of age. Microarray and gene set enrichment
      analysis highlighted decreased function of the electron transport chain as
      characteristic of both aging muscle and loss of Pgc-1alpha expression. Despite
      significant reductions in oxidative gene expression and succinate dehydrogenase
      activity, young mice lacking Pgc-1alpha in muscle had lower fasting glucose and
      insulin. Consistent with loss of oxidative capacity during aging, Pgc-1alpha and
      Pgc-1beta expression were reduced in aged wild-type mouse muscle. Interestingly,
      the combination of age and loss of muscle Pgc-1alpha expression impaired glucose
      tolerance and led to increased fat mass, insulin resistance, and inflammatory
      markers in white adipose and liver tissues. Therefore, loss of Pgc-1alpha
      expression and decreased mitochondrial oxidative capacity contribute to worsening
      glucose tolerance and chronic systemic inflammation associated with aging. 

PMID- 24280129
TI  - A.S.P.E.N. parenteral nutrition safety consensus recommendations.
AB  - Parenteral nutrition (PN) serves as an important therapeutic modality that is
      used in adults, children, and infants for a variety of indications. The
      appropriate use of this complex therapy aims to maximize clinical benefit while
      minimizing the potential risks for adverse events. Complications can occur as a
      result of the therapy and as the result of the PN process. These consensus
      recommendations are based on practices that are generally accepted to minimize
      errors with PN therapy, categorized in the areas of PN prescribing, order review
      and verification, compounding, and administration. These recommendations should
      be used in conjunction with other A.S.P.E.N. publications, and researchers should
      consider studying the questions brought forth in this document. 

PMID- 24280128
TI  - NF-kappaB and STAT1 control CXCL1 and CXCL2 gene transcription.
AB  - Diabetes mellitus results from immune cell invasion into pancreatic islets of
      Langerhans, eventually leading to selective destruction of the insulin-producing
      beta-cells. How this process is initiated is not well understood. In this study,
      we investigated the regulation of the CXCL1 and CXCL2 genes, which encode
      proteins that promote migration of CXCR2(+) cells, such as neutrophils, toward
      secreting tissue. Herein, we found that IL-1beta markedly enhanced the expression
      of the CXCL1 and CXCL2 genes in rat islets and beta-cell lines, which resulted in
      increased secretion of each of these proteins. CXCL1 and CXCL2 also stimulated
      the expression of specific integrin proteins on the surface of human neutrophils.
      Mutation of a consensus NF-kappaB genomic sequence present in both gene promoters
      reduced the ability of IL-1beta to promote transcription. In addition, IL-1beta
      induced binding of the p65 and p50 subunits of NF-kappaB to these consensus
      kappaB regulatory elements as well as to additional kappaB sites located near the
      core promoter regions of each gene. Additionally, serine-phosphorylated STAT1
      bound to the promoters of the CXCL1 and CXCL2 genes. We further found that IL
      1beta induced specific posttranslational modifications to histone H3 in a time
      frame congruent with transcription factor binding and transcript accumulation. We
      conclude that IL-1beta-mediated regulation of the CXCL1 and CXCL2 genes in
      pancreatic beta-cells requires stimulus-induced changes in histone chemical
      modifications, recruitment of the NF-kappaB and STAT1 transcription factors to
      genomic regulatory sequences within the proximal gene promoters, and increases in
      phosphorylated forms of RNA polymerase II. 

PMID- 24280130
TI  - Improved outcomes with direct percutaneous CT guided lumbar synovial cyst
      treatment: advanced approaches and techniques.
AB  - PURPOSE: To determine if lumbar synovial cyst rupture in symptomatic patients
      results in improved clinical outcome when using direct tandem and/or coaxial
      percutaneous CT guided techniques. MATERIALS AND METHODS: 20 patients with
      unilateral lower extremity radiculopathy and/or low back pain underwent CT guided
      percutaneous treatment for their symptomatic lumbar synovial cysts. Cysts were
      identified with the use of a low osmolar non-ionic contrast agent via facet joint
      injection or through direct injection. Cyst rupture, using a direct tandem and/or
      coaxial technique, was attempted in all patients using an 18 gauge guide needle
      and a 22 gauge insert needle. Following attempted cyst aspiration, cyst rupture
      was performed using 1-3 mL of a mixture of methylprednisolone (2 mL, 80 mg) and
      bupivacaine (3 mL, 0.5%). All patients were followed-up in clinic for a minimum
      of 6 months after their procedures and up to a maximum of 24 months. RESULTS: 11
      patients were male and nine were female, with an average age of 65.6 years. 17
      patients presented with severe unilateral lower extremity radiculopathy and three
      patients were experiencing low back pain. One of the patients had two synovial
      cysts, and therefore a total of 21 lumbar synovial cysts were treated in this
      group of patients. Direct cyst puncture was achieved using a tandem technique in
      nine patients, a coaxial interlaminar approach in seven patients, a coaxial
      transforaminal approach in two patients, and a coaxial trans-facet approach in
      three patients. Cyst rupture was documented in all cases, as evidenced by CT
      confirmation of cyst decompression and contrast agent extravasation into the
      epidural space. The mean surveillance period in these patients was 18 months. Six
      patients experienced their usual radicular pain within 2 months of their
      treatment. Four of these patients were re-treated for recurrent smaller cysts.
      These patients have not had a recurrence at 24 months of follow up. Two of these
      six patients elected to undergo open surgical decompression without symptomatic
      improvement. No treatment related complications were observed in this group of
      patients. CONCLUSIONS: Direct tandem and/or coaxial percutaneous CT guided
      techniques for rupture and treatment of symptomatic lumbar synovial cysts reduces
      recurrence rates and therefore helps avoid more invasive open surgical procedures
      in this group of patients.

PMID- 24280131
TI  - Genome-wide identification and analysis of miRNA-related single nucleotide
      polymorphisms (SNPs) in rice.
AB  - BACKGROUND: MiRNAs are key regulators in the miRNA-mediated regulatory networks.
      Single nucleotide polymorphisms (SNPs) that occur at miRNA-related regions may
      cause serious phenotype changes. To gain new insights into the evolution of
      miRNAs after SNP variation, we performed a genome-wide scan of miRNA-related
      SNPs, and analyzed their effects on the stability of miRNAs structure and the
      alteration of target spectrum in rice. RESULTS: We find that the SNP density in
      pre-miRNAs is significantly higher than that in the flanking regions, owing to
      the rapid evolution of a large number of species-specific miRNAs in rice. In
      contrast, it is obvious that deeply conserved miRNAs are under strong purifying
      selection during evolution. In most cases, the SNPs in stem regions may result in
      the miRNA hairpin structures changing from stable to unstable status; And SNPs in
      mature miRNAs have great potential to have either newly created or disrupted the
      miRNA-target interactions. However, the total number of gained targets is over
      2.5 times greater than that are lost after mutation. Notably, 12 putative
      domestication-related miRNAs have been identified, where the SNP density is
      significantly lower. CONCLUSIONS: The present study provides the first outline of
      SNP variations occurred in rice pre-miRNAs at the whole genome-wide level. These
      analyses may deepen our understanding on the effects of SNPs on the evolution of
      miRNAs in the rice genome.

PMID- 24280132
TI  - Estradiol enhances CIP2A expression by the activation of p70 S6 kinase.
AB  - Cancerous inhibitor of PP2A (CIP2A) stimulates the proliferation of various
      cancer cells, and 17beta-estradiol (E2) enhances the proliferation of breast
      cancer cells. E2 activates epidermal growth factor receptor (EGFR), stimulating
      the MEK1/2 and PI3K pathways, and CIP2A expression is increased by the MEK1/2
      induced transcription factor ETS1. It is possible for E2 to increase CIP2A
      expression. This study examined whether E2 could increase CIP2A expression and
      whether CIP2A is highly expressed in estrogen receptor (ER)-positive breast
      cancer tissues. E2 increased CIP2A expression at the translational level in a c
      MYC-independent manner in MCF-7 cells. E2-enhanced proliferation was impaired
      without CIP2A expression. E2-stimulated EGFR activated the MAPK and PI3K
      pathways, which converged to activate p70 S6 kinase (S6K). Phosphorylation at all
      the three phosphorylation sites (S424/T421, T229, and T389) on S6K was required
      for the phosphorylation of eukaryotic initiation factor 4B (eIF4B), which was
      responsible for the increase in CIP2A translation. Furthermore, CIP2A expression
      was higher in ER-positive tissues than in ER-negative tissues. This is the first
      study, to our knowledge, to demonstrate that CIP2A is a key factor in E2-enhanced
      proliferation and that estrogen regulates CIP2A expression by non-genomic action
      through EGFR.

PMID- 24280134
TI  - Actions of endocrine-disrupting chemicals on stem/progenitor cells during
      development and disease.
AB  - Development and fate of the stem cell are regulated by extrinsic signals from the
      environment. Endocrine-disrupting chemicals which perturb hormonal signaling in
      utero and during early childhood may cause deregulation of multiple developmental
      processes, ranging from breakdown of stem cell niche architecture, developmental
      reprograming and altered stem cell fate to impaired organ and gonad development
      and sexual differentiation. Therefore, study of the environmental effects on stem
      cell integrity and normal development is a new and emerging focus for
      developmental biologists and cell toxicologists. When combined with new human and
      mouse stem cell-based models, stem cell differentiation dynamics can be studied
      in more biologically relevant ways. In this study, we review the current status
      of our understanding of the molecular mechanisms by which endocrine disruptors
      alter embryonic stem cell and adult stem/progenitor cell fate, organ development,
      cancer stem cell activity, and tumorigenesis. 

PMID- 24280133
TI  - SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate
      cancer.
AB  - Deregulation of cytokine and growth factor signaling due to an altered expression
      of endogenous regulators is well recognized in prostate cancer (PCa) and other
      cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of the GH,
      IGF, and prolactin signaling pathways that have been implicated in
      carcinogenesis. In this study, we evaluated the expression patterns and
      functional significance of SOCS2 in PCa. Protein expression analysis employing
      tissue microarrays from two independent patient cohorts revealed a significantly
      enhanced expression in tumor tissue compared with benign tissue as well as
      association with Gleason score and disease progression. In vitro and in vivo
      assays uncovered the involvement of SOCS2 in the regulation of cell growth and
      apoptosis. Functionally, SOCS2 knockdown inhibited PCa cell proliferation and
      xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation
      was associated with cell-cycle arrest and apoptosis. In addition, we proved that
      SOCS2 expression is significantly elevated upon androgenic stimulation in
      androgen receptor (AR)-positive cell lines, providing a possible mechanistic
      explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression
      correlated with AR expression in the malignant tissue of patients. On the whole,
      our study linked increased SOCS2 expression in PCa with a pro-proliferative role
      in vitro and in vivo. 

PMID- 24280135
TI  - Prevalence and types of coronary to pulmonary artery fistula in a Chinese
      population at dual-source CT coronary angiography.
AB  - BACKGROUND: Coronary to pulmonary artery fistula (CPAF) is rare; reports on the
      prevalence and types of CPAF in a large cohort of patients are scarce. PURPOSE:
      To analyze the prevalence and types of CPAF on computed tomography coronary
      angiography (CTCA) in a large Chinese population. MATERIAL AND METHODS: CTCA data
      of 58,533 patients from five Chinese tertiary referral medical centers were
      retrospectively studied. The prevalence, origin, aneurysmal sac, fistula tracts,
      and extracardiac communication of CPAF were recorded. CTCA findings were compared
      with conventional coronary angiography when possible. RESULTS: Ninety-nine
      patients had CPAF (prevalence of 0.17%). Of the 99 CPAF cases, fistulas were
      found to originate from either both coronary arteries in 52 patients or from one
      coronary artery (33 cases from the left and 14 cases from the right coronary
      artery). Ten CPAF patients were complicated with the communication of
      extracardiac arteries. Fifteen (15.2%) CPAF patients had aneurysmal sac
      formation. Thirty (30.3%) patients had a single fistula tract, while 69 (69.7%)
      patients had multiple fistula tracts. CTCA findings in 16 patients were similar
      to those at DSA. CONCLUSION: Based on this large cohort, the prevalence of CPAF
      in the Chinese population is about 0.17%, with origin from either the left or
      right coronary artery or from both. CTCA can clearly visualize the types,
      abnormal vascular tracts, and aneurysmal sac formation of CPAF.

PMID- 24280136
TI  - Chest CT findings of pleural tuberculosis: differential diagnosis of pleural
      tuberculosis and malignant pleural dissemination.
AB  - BACKGROUND: The imaging features of pleural tuberculosis (PTB) can be similar to
      those of malignant pleural dissemination (MPD) with several case reports of CT
      findings in atypical presentations of PTB. PURPOSE: To describe the computed
      tomography (CT) features of PTB by comparing these imaging findings with those of
      MPD and to use the results to differentiate between the two diseases. MATERIAL
      AND METHODS: The study included 135 patients with PTB and 69 with MPD. The CT
      images were assessed in terms of the presence, extent, and contour of pleural
      thickening. Pleural nodules were analyzed in terms of number, size, and location.
      The CT findings of PTB and MPD were compared. RESULTS: The CT findings of PTB
      included circumferential pleural thickening (32.6%), mediastinal pleural
      involvement (31.9%), nodular thickening (8.9%), and pleural thickening >1 cm
      (2.2%). The CT features of MPD included nodular pleural thickening (56.5%),
      mediastinal pleural involvement (40.6%), circumferential thickening (23.2%), and
      pleural thickening >1 cm (7.2%). Comparing PTB and MPD, nodular pleural
      thickening was observed more frequently with MPD than PTB (P <0.001). CONCLUSION:
      Nodular pleural thickening is observed in 8.9% of the patients with PTB on chest
      CT. Comparing PTB and MPD, nodular pleural thickening was the only finding
      significantly associated with MPD, particularly with nodules >10 mm.

PMID- 24280137
TI  - Is balloon kyphoplasty better than percutaneous vertebroplasty for osteoporotic
      vertebral biconcave-shaped fractures?
AB  - BACKGROUND: Osteoporotic vertebral biconcave-shaped fractures are not commonly
      seen in clinical practice. Some articles have been published showing the outcome
      of vertebroplasty (PV) and balloon kyphoplasty (BKP), but few comparative studies
      have been performed. PURPOSE: To compare the effect and safety of PV and BKP in
      treating osteoporotic vertebral biconcave-shaped fractures. MATERIAL AND METHODS:
      In this retrospective comparative study, 38 patients with osteoporotic vertebral
      biconcave-shaped fractures were treated by PV, and 41 patients were treated by
      BKP from May 2005 to July 2011. The heights of the compromised vertebral body and
      the kyphotic angles were measured. Visual analogue scale (VAS) and Oswestry
      Disability Index (ODI) were used to evaluate pain and functional activity,
      respectively. The occurrence of refracture and cement leakage were determined,
      and the costs were recorded. RESULTS: The mean VAS and ODI scores significantly
      improved for both procedures at postsurgical measurements (P < 0.05), and the
      improvement sustained at the final follow-up. In both groups, there were no
      significant differences in terms of restoration of the anterior vertebral height
      and correction of the kyphotic deformity. However, BKP was more effective in
      restoring the middle vertebral height than PV. Cement leakages were observed in
      nine (23.7%) treated vertebral bodies in PV group and in three (7.4%) treated
      vertebral bodies in BKP group, which was a statistically significant difference
      (P < 0.05). There were four new osteoporotic vertebral fractures in the PV group
      and two in the BKP group during the follow-up period. The mean cost in the BKP
      group (6200 +/- 122.1 USD) was higher than the PV group (2100 +/- 112.5 USD) (P <
      0.05). CONCLUSION: Both PV and BKP achieved similar improvements in pain and
      functional outcomes for the treatment of osteoporotic vertebral biconcave-shaped
      fractures. BKP had a significant advantage over PV in terms of the restoration of
      the middle vertebral height and fewer cement leakages than PV.

PMID- 24280139
TI  - Histological evaluation of the role of atypical antipsychotic drugs in inducing
      non-alcoholic fatty liver disease in adult male albino rats (light and electron
      microscopic study).
AB  - Many of atypical antipsychotic drugs are associated with adverse metabolic
      effects, including fatty infiltration of the liver. This study aimed at studying
      the histological evaluation of the role of atypical antipsychotic drugs
      (olanzapine and aripiprazole) in adult male albino rats. Sixty adult male albino
      rats were divided equally into three groups. Group I served as a control while
      groups II and III were treated with olanzapine and aripiprazole consecutively.
      Sections of the liver were examined by light and electron microscopy. A highly
      significant increase in the weight of rats in olanzapine- and aripiprazole-
      treated groups in comparison to the control group was noticed. On the other hand,
      there was a highly significant increase in body weight of the olanzapine group in
      comparison to aripiprazole. Olanzapine- and aripiprazole-treated rats showed
      highly significantly increased fatty infiltration of liver (steatosis) compared
      with the control group. However, the aripiprazole-treated group showed less
      steatosis compared with olanzapine. The mean non-alcoholic steatohepatitis
      scoring and fibrosis of the olanzapine group were highly significantly increased
      compared to the aripiprazole group. Ultrastructurally, liver from the olanzapine
      group showed large fat droplets in perinuclear region, between cisternae of the
      rough endoplasmic reticulum, and in the space of Disse. Large-sized mitochondria
      and myelin figures were seen. Although histopathological changes of the liver in
      the form of non-alcoholic fatty liver disease were more prominent in the
      olanzapine group, they were also evident in the aripiprazole group. 

PMID- 24280138
TI  - Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6
      bisphosphatases in cancer metabolism.
AB  - The increased glucose metabolism in cancer cells is required to fulfill their
      high energetic and biosynthetic demands. Changes in the metabolic activity of
      cancer cells are caused by the activation of oncogenes or loss of tumor
      suppressors. They can also be part of the metabolic adaptations to the conditions
      imposed by the tumor microenvironment, such as the hypoxia response. Among the
      metabolic enzymes that are modulated by these factors are the 6-phosphofructo-2
      kinase/fructose 2,6-bisphosphatases (PFKFBs), a family of bifunctional enzymes
      that control the levels of fructose 2,6-bisphosphate (Fru-2,6-P2). This
      metabolite is important for the dynamic regulation of glycolytic flux by
      allosterically activating the rate-limiting enzyme of glycolysis
      phosphofructokinase-1 (PFK-1). Therapeutic strategies designed to alter the
      levels of this metabolite are likely to interfere with the metabolic balance of
      cancer cells, and could lead to a reduction in cancer cell proliferation,
      invasiveness and survival. This article will review our current understanding of
      the role of PFKFB proteins in the control of cancer metabolism and discuss the
      emerging interest in these enzymes as potential targets for the development of
      antineoplastic agents. 

PMID- 24280140
TI  - Serum levels of matrix metalloproteinases 2 and 9 in patients with acute
      myocardial infarction.
AB  - The myocardial extracellular matrix plays an important role in maintaining the
      structural and functional integrity of the heart and is centrally involved in
      post-myocardial infarction repair processes. We analysed some genetic and
      proteomic aspects that could play an important role in the development of
      myocardial infarction. Matrix metalloproteinases are enzymes that contribute
      strongly to the degradation of extracellular matrix components. In this study the
      serological levels of MMP-2 and MMP-9 were investigated using immunological
      testing in 34 patients with myocardial infarction and 34 matched control
      subjects. The serum levels of MMPs were determined by ELISA. Changes in serum
      levels were characterized within 24 h and after 6 months post myocardial
      infarction. Significantly higher levels of MMP-2 (299.47 +/- 117.61 ng/ml) and
      MMP-9 (93.56 +/- 53.74 ng/ml) were determined in patients with myocardial
      infarction compared to the controls, in both cases P < 0.001. MMP-9 levels
      decreased significantly in the 6 months after cardiac event, whereas the levels
      of MMP-2 were almost equal to the post-infarction ones. While comparing the
      results from four patients that died of cardiovascular cause within 6 months we
      found significantly higher MMP-2 (435.00 +/- 55.83 ng/ml, P = 0.003) and MMP-9
      (166.25 +/- 41.07 ng/ml, P = 0.018) values. Microarray analysis was used to
      determine the gene expression of selected genes for MMPs and their regulators
      from peripheral blood. The selected genes did not show satisfactory results that
      could have a potential implication for diagnostics of tissue degeneration. 

PMID- 24280141
TI  - Ionizing radiation induces senescence and differentiation of human dental pulp
      stem cells.
AB  - Head and neck cancer is one of the most common cancers in Europe. Many current
      anti-cancer treatments, including ionizing radiation, induce apoptosis via DNA
      damage. Unfortunately, such treatments are non-selective to cancer cells and
      produce similar toxicity in normal cells, including adult stem cells. One of the
      fundamental properties of an adult stem cell is that it does not have any tissue
      specific structures that allow it to perform specialized functions. However,
      under certain stimuli, unspecialized adult stem cells can give rise to
      specialized cells to generate replacements for cells that are lost during one's
      life or due to injury or disease. Nevertheless, specialization of stem cells must
      be controlled by specific milieu and also initiated at the proper time, making
      the entire process beneficial for tissue recovery and maintaining it for a long
      time. In this paper we assess whether irradiated dental pulp stem cells have
      maintained open their options to mature into specialized cells, or whether they
      have lost their unspecialized (immature) state following irradiation. Our
      findings showed radiation-induced premature differentiation of dental pulp stem
      cells towards odonto-/osteoblast lineages in vitro. Matrix calcification was
      visualized from Day 6 or Day 9 following irradiation of cells expressing low or
      high levels of CD146, respectively. 

PMID- 24280142
TI  - Immunodominant semen proteins II: contribution of seminal proteins to female
      immune infertility.
AB  - Seminal fluid is a protective medium for sperm, but it also represents potential
      immunogenic structures for the female immune system. Anti-seminal antibodies may
      threaten early fertilization. The aim of our work is to detect and identify
      seminal proteins that are related to female isoimmunization. In this report, we
      quantified serum anti-seminal IgG antibodies. Seminal proteins were analysed by
      two-dimensional gel electrophoresis followed by immunoblotting. To identify IgG
      binding proteins of interest, a proteomic approach was selected. The dominant
      seminal antigens were detected within the relative molecular mass ranging from 25
      to 85 kDa and the isoelectric point from 5 to 7. The detected proteins were
      further identified as prostate-specific antigen, prostatic acid phosphatase, zinc
      alpha-2-glycoprotein and zinc finger protein 778. Since these proteins were
      recognized by IgGs produced by infertile women and not by fertile women, we
      presume that major seminal antigens may play an important role in the
      pathogenesis of female immune infertility. Our study suggests the pattern of
      seminal proteins for further therapeutic attempts in the diagnosis of female
      immune infertility.

PMID- 24280143
TI  - RHOA, SEMA3B, and CKAP2 expression in leukaemia of different types: the results
      of a pilot experiment.
AB  - The transcriptional activity of RHOA, SEMA3B, and CKAP2 genes was assessed in
      blood samples of leukaemia patients and healthy donors. In the blood of healthy
      donors, RHOA and CKAP2 gene expression was not detected, and low SEMA3B gene
      expression was observed. Significant elevation of expression of all the three
      genes was shown in the case of acute myelogenous leukaemia. In cases of remission
      of acute lymphoblastic leukaemia and myelodysplastic syndrome, no expression of
      all three genes was detected. The long isoform of the CKAP2 gene was highly
      expressed in most analysed types of leukaemia. 

PMID- 24280144
TI  - Guidelines to site selection for population surveillance and mosquito control
      trials: a case study from Mauritius.
AB  - Many novel approaches to controlling mosquito vectors through the release of
      sterile and mass reared males are being developed in the face of increasing
      insecticide resistance and other limitations of current methods. Before full
      scale release programmes can be undertaken there is a need for surveillance of
      the target population, and investigation of parameters such as dispersal and
      longevity of released, as compared to wild males through mark-release-recapture
      (MRR) and other experiments, before small scale pilot trials can be conducted.
      The nature of the sites used for this field work is crucial to ensure that a
      trial can feasibly collect sufficient and relevant information, given the
      available resources and practical limitations, and having secured the correct
      regulatory, community and ethical approvals and support. Mauritius is considering
      the inclusion of the sterile insect technique (SIT), for population reduction of
      Aedes albopictus, as a component of the Ministry of Health and Quality of Life's
      'Operational Plan for Prevention and Control of Chikungunya and Dengue'. As part
      of an investigation into the feasibility of integrating the SIT into the
      Integrated Vector Management (IVM) scheme in Mauritius a pilot trial is planned.
      Two potential sites have been selected for this purpose, Pointe des Lascars and
      Panchvati, villages in the North East of the country, and population surveillance
      has commenced. This case study will here be used to explore the considerations
      which go into determining the most appropriate sites for mosquito field research.
      Although each situation is unique, and an ideal site may not be available, this
      discussion aims to help researchers to consider and balance the important factors
      and select field sites that will meet their needs. 

PMID- 24280145
TI  - Influence of Mansonella perstans microfilaraemia on total IgE levels in Gabonese
      patients co-infected with Loa loa.
AB  - Mansonella (M.) perstans filariasis is widely found in Africa, including Gabon
      where Loa loa is also endemic. This study reports the total IgE titres according
      to different bioclinical forms of single or co-infection with L. loa and M.
      perstans in 138 patients and 20 healthy controls. The median parasite density was
      significantly higher in cases of loiasis. IgE titres were higher in patients with
      microscopic dual-infection and in the group of patients with occult loiasis plus
      M. perstans microfilaraemia (8425 [5292-20,679]KUI/L and 6304 [1045-10,326]KUI/L,
      respectively), compared to individuals with either microfilaraemic Loa loa (3368
      [1414-7074]KUI/L) or Mansonella (4370 [1478-7334]KUI/L) single infections
      (p<0.01). IgE levels were positively correlated with M. perstans microfilaraemia
      (rho=0.27; p<0.01). Compared to single infections, dual M. perstans-L. loa
      infection induces very high total IgE titres. Studies correlating IgE titres and
      clinical symptoms are needed to confirm the involvement of this immunoglobulin in
      the pathological processes during filariasis. 

PMID- 24280146
TI  - Unexpected detection of bovine G10 rotavirus in a Brazilian child with diarrhea.

PMID- 24280147
TI  - Predictive factors for failure of percutaneous drainage of postoperative abscess
      after abdominal surgery.
AB  - BACKGROUND: The aims of this study were to assess the efficacy of percutaneous
      drainage of postoperative abscess after abdominal surgery and to identify factors
      predictive of failed drainage. METHODS: Data from 81 patients with postoperative
      abdominopelvic abscesses treated with percutaneous drainage were reviewed.
      Percutaneous drainage failure was considered when surgery was needed to control
      the sepsis. Predictive variables were sought using univariate and multivariate
      analyses with logistic regression models. RESULTS: Successful drainage requiring
      1 (n = 46) or 2 (n = 17) procedures was observed in 63 patients (78%; 95%
      confidence interval, 67%-86%). Surgery was needed in 18 patients (22%; 95%
      confidence interval, 14%-38%). Residual collection after a first percutaneous
      drainage was the single predictive factor for failed drainage on univariate and
      multivariate analyses (P = .0275). CONCLUSIONS: Percutaneous imaging-guided
      drainage is a feasible and effective method for the treatment of abdominopelvic
      abscess, with a success rate of 78%. Residual collection is an independent
      predictor of unfavorable outcome after percutaneous drainage.

PMID- 24280148
TI  - Amyand's hernia: a review.
AB  - BACKGROUND: The presence of a vermiform appendix in an inguinal hernia sac is
      known as Amyand's hernia. The aim of this systematic review was to gather
      information concerning its prevalence, clinical image, diagnosis, and treatment.
      DATA SOURCES: The MEDLINE database was thoroughly searched using the keyword
      "Amyand's hernia." Additional articles were gathered and evaluated. CONCLUSIONS:
      The true prevalence of Amyand's hernia seems lower than classically described.
      Its usual clinical image is identical to that of an incarcerated hernia, and thus
      it is almost impossible to diagnose preoperatively, although ultrasound and
      computed tomography can help. Treatment includes hernioplasty with or without
      appendectomy and/or mesh repair depending on the vermiform appendix's
      inflammation status, the patient's general condition, and other factors. Amyand's
      hernia generally has a good prognosis, although serious complications have been
      described. Surgeons should be prepared if they encounter Amyand's hernia because
      appropriate treatment ensures hernia repair without complications and with
      avoidance of recurrence.

PMID- 24280149
TI  - Improvement of photosynthesis in rice (Oryza sativa L.) by inserting the C4
      pathway.
AB  - To boost food production for a rapidly growing global population, crop yields
      must significantly increase. One of the avenues being recently explored is the
      improvement of photosynthetic capacity by installing the C4 photosynthetic
      pathway into C3 crops like rice to drastically increase their yield. Crops with
      an enhanced photosynthetic mechanism would better utilize the solar radiation
      that can be translated into yield. This subsequently will help in producing more
      grain yield, reduce water loss and increase nitrogen use efficiency especially in
      hot and dry environments. This review provides a summary of the factors that need
      to be modified in rice so that the C4 pathway can be introduced successfully. It
      also discusses the differences between the C3 and C4 photosynthetic pathways in
      terms of anatomy, biochemistry and genetics. 

PMID- 24280150
TI  - Subclinical psychosis syndromes in the general population: results from a large
      scale epidemiological survey among residents of the canton of Zurich,
      Switzerland.
AB  - Aims. Prevalence and covariates of subclinical psychosis have gained increased
      interest in the context of early identification and treatment of persons at risk
      for psychosis. Methods. We analysed 9829 adults representative of the general
      population within the canton of Zurich, Switzerland. Two psychosis syndromes,
      derived from the SCL-90-R, were applied: 'schizotypal signs' and 'schizophrenia
      nuclear symptoms'. Results. Only a few subjects (13.2%) reported no schizotypal
      signs. While 33.2% of subjects indicated mild signs, only a small proportion
      (3.7%) reported severe signs. A very common outcome was no 'schizophrenia nuclear
      symptoms' (70.6%). Although 13.5% of the participants reported mild symptoms,
      severe nuclear symptoms were very rare (0.5%). Because these two syndromes were
      only moderately correlated (r = 0.43), we were able to establish sufficiently
      distinct symptom clusters. Schizotypal signs were more closely connected to
      distress than was schizophrenia nuclear symptoms, even though their distribution
      types were similar. Both syndromes were associated with several covariates, such
      as alcohol and tobacco use, being unmarried, low education level,
      psychopathological distress and low subjective well-being. Conclusions.
      Subclinical psychosis symptoms are quite frequent in the general population but,
      for the most part, are not very pronounced. In particular, our data support the
      notion of a continuous Wald distribution of psychotic symptoms in the general
      population. Our findings have enabled us to confirm the usefulness of these
      syndromes as previously assessed in other independent community samples. Both can
      appropriately be associated with well-known risk factors of schizophrenia. 

PMID- 24280151
TI  - Asia rising.

PMID- 24280152
TI  - Kissing vanishing stents: are we trading ephemeral benefit for permanent damage?

PMID- 24280153
TI  - Management of recurrent in-stent restenosis: onion skin full metal jacket?

PMID- 24280154
TI  - The EAPCI welcomes the new WOMEN initiative.

PMID- 24280155
TI  - Optimal treatment of recurrent restenosis lesions after drug-eluting stent
      implantation for in-stent restenosis lesions.
AB  - AIMS: Although the outcomes of various treatments for in-stent restenosis (ISR)
      after drug-eluting stent (DES) implantation have been reported, the optimal
      treatment of recurrent ISR lesions after DES implantation for ISR lesions was
      unknown. This study compared the efficacy between DES implantation and balloon
      angioplasty (BA) for recurrent ISR lesions after DES implantation. METHODS AND
      RESULTS: From 2003 to 2010, DES were implanted in 1,101 ISR lesions, of which 148
      recurrent ISR lesions (142 patients) were treated with BA (76 lesions, 72
      patients) and DES implantation (72 lesions, 70 patients). Clinical outcomes were
      evaluated for major adverse cardiac events (MACE), including a composite of
      death, myocardial infarction, and target lesion revascularisation (TLR).
      Angiographic outcomes were evaluated by follow-up angiography at six to eight
      months after procedure. At angiographic follow-up (94.4% of all patients), the
      binary restenosis rate was significantly lower in DES implantation (25.0%) than
      in BA (64.4%, p<0.001), whereas late lumen loss was similar between DES
      implantation and BA (0.80+/-0.78 mm vs. 0.87+/-0.79 mm, p=0.60). The incidence of
      four-year MACE was significantly higher in BA (75.2%) than in DES implantation
      (45.8%, p<0.001), mainly because of the lower TLR rate in DES implantation (60.5%
      vs. 27.6%, p<0.001). Multivariate analysis revealed that BA is an independent
      predictor of TLR, followed by non-focal lesion, non-intravascular ultrasound
      guidance, and dyslipidaemia. CONCLUSIONS: In the treatment of recurrent ISR
      lesions, DES implantation is markedly more effective with a lower incidence of
      TLR compared to BA.

PMID- 24280156
TI  - Coronary artery bypass graft versus percutaneous coronary intervention with drug
      eluting stent implantation for diabetic patients with unprotected left main
      coronary artery disease: the D-DELTA registry.
AB  - AIMS: Data regarding the impact on clinical outcomes of PCI with DES implantation
      vs. CABG to treat unprotected left main coronary artery (ULMCA) disease in
      diabetic patients are still insufficient. The present study evaluated the short
      term and long-term results of percutaneous and surgical revascularisation in
      diabetic patients with ULMCA disease in a large population. METHODS AND RESULTS:
      A total of 826 diabetic patients with ULMCA stenosis who received DES (n=520) or
      underwent CABG (n=306) were selected and analysed from the DELTA registry. In
      hospital MACCE was significantly higher in the CABG group, mainly driven by a
      higher incidence of MI. At four-year follow-up, freedom from death and the
      composite endpoint of death, MI and cerebrovascular accident (CVA) was similar in
      the two treatment groups (CABG 87.4%, PCI 82.5%, p=0.124, and CABG 85.4%, PCI
      78.9%, p=0.11, respectively). Conversely, freedom from TVR and MACCE was
      significantly higher in the CABG compared to the PCI group (CABG 95.4%, PCI
      79.4%, p<0.001, and CABG 81.9%, PCI 64.7%, p<0.001). CONCLUSIONS: In diabetic
      patients with ULMCA disease with/without concomitant multivessel disease, PCI and
      CABG led to similar results in terms of death, MI and CVA. However, CABG was
      associated with less MACCE at long-term follow-up, primarily due to the higher
      repeat revascularisation rate with DES.

PMID- 24280157
TI  - Two-year outcomes following unprotected left main stenting with first vs. new
      generation drug-eluting stents: the FINE registry.
AB  - AIMS: To assess two-year outcomes following first vs. new-generation drug-eluting
      stent (DES) implantation in unprotected left main (ULMCA) percutaneous coronary
      intervention. METHODS AND RESULTS: All eligible patients from our two-centre
      registry treated with first and new-generation DES from October 2006 to November
      2010 were analysed. The study objective was major adverse cardiac events (MACE),
      defined as all-cause mortality, target vessel revascularisation (TVR) and
      myocardial infarction (MI) at two years. In total, 186 patients were included: 93
      (50.0%) treated with first vs. 93 (50.0%) with new-generation DES. No differences
      were observed in baseline clinical characteristics except for higher EuroSCORE
      with new-generation DES (3.6+/-2.5 vs. 4.6+/-2.7; p=0.007). No significant
      difference was observed in stenting techniques; two stents were used respectively
      in 53.8% vs. 44.1% (p=0.187). Notably, intravascular ultrasound guidance was more
      frequent with new-generation DES (46.2% vs. 61.3%; p=0.040). At 730.0
      (interquartile range 365.5-1,224.5) days, there was a trend towards improved MACE
      with new-generation DES (31.2% vs. 19.6%; p=0.070) and a significant reduction in
      TVR (23.7% vs. 12.0%; p=0.038) and MI (4.3% vs. 0%; p=0.044). Notably, there were
      four cases of definite stent thrombosis (ST) with first vs. none with new
      generation DES (p=0.044). CONCLUSIONS: In our study, new-generation DES had a
      trend for less MACE and improved results with regard to MI, TVR and definite ST
      at two-year follow-up.

PMID- 24280158
TI  - Impact of bifurcation target lesion on angiographic, electrocardiographic, and
      clinical outcomes of patients undergoing primary percutaneous coronary
      intervention (from the Harmonizing Outcomes With Revascularization and Stents in
      Acute Myocardial Infarction [HORIZONS-AMI] trial).
AB  - AIMS: Using the database from the large-scale, prospective, randomised HORIZONS
      AMI trial, the authors sought to assess the impact of bifurcation target lesions
      (BTL) on angiographic, electrocardiographic, and clinical outcomes in patients
      with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: In HORIZONS-AMI, bifurcation
      lesions in which a provisional approach was planned were eligible for enrolment.
      By angiographic core laboratory assessment of 3,306 patients with STEMI
      undergoing primary PCI, 333 patients (10%) had >=1 BTL, and 2,973 patients had no
      BTL. There were no significant differences in baseline characteristics between
      the groups, except for lower left ventricular ejection fraction and more frequent
      left anterior descending infarct artery in the BTL group. BTLs required longer
      procedural and fluoroscopy times and higher contrast loads, but rates of TIMI 3
      flow post PCI were similar in both groups (with vs. without BTL 99% vs. 87%,
      p=0.25). ST-segment resolution >=70% by core laboratory analysis was similar in
      both groups (48% vs. 50%, p=0.47). Importantly, there was no difference between
      groups in the rate of death (6.1% vs. 6.7%, p=0.72), definite or probable stent
      thrombosis (4.2% vs. 5.2%, p=0.42), and ischaemic target vessel revascularisation
      (14.3% vs. 14.0%, p=0.86) during three-year follow-up. CONCLUSIONS: Although the
      PCI procedure involving BTL was more complex, the acute results and late outcomes
      in patients with BTLs were comparable to those in patients without BTLs.

PMID- 24280159
TI  - Integrated x-ray and echocardiography imaging for structural heart interventions.
AB  - Treatment of structural heart disease (SHD) represents a growing need and, with
      increasing device availability, an increasing number of SHD can be and will be
      treated percutaneously. However, interventional treatment of SHD is challenging.
      Long procedure times and steep learning curves are recognised obstacles. The main
      difficulties arise, however, from the inability to visualise simultaneously the
      anatomy and the devices using a single imaging technology. In fact, the majority
      of percutaneous interventions in SHD are guided by fluoroscopy. On the other
      hand, a multitude of imaging technologies are presently available to guide the
      interventionalist. Of these technologies, transoesophageal echocardiography
      (TEE), and particularly 3-D TEE, is rapidly becoming the imaging modality of
      choice for many of these procedures because it provides critical insights into
      soft tissue anatomy. However, adequate visualisation and appreciation of the
      relationships between the cardiac structures and the devices using various
      imaging modalities remain a challenge. Hence, the interaction between the
      operator and imager is a crucial factor in attaining procedural success.
      Innovative technology that fuses live 3-D TEE with live x-ray in an intuitive way
      could have an important added value. This new imaging technology seeks to improve
      the communication between the echocardiographer and the interventionalist, to
      increase the confidence and anatomical awareness, to assist in guidance, and to
      increase procedural efficiency. 

PMID- 24280160
TI  - Microcatheter-facilitated reverse wire technique for side branch wiring in
      bifurcated vessels: an in vitro evaluation.
AB  - AIMS: To assess when and how the microcatheter-facilitated reverse wire technique
      should be applied to cross the guidewire into side branches in coronary
      bifurcations. METHODS AND RESULTS: Three interventional cardiologists with
      different levels of experience performed in vitro bench testing using an
      originally developed coronary bifurcation simulator which had six coronary
      bifurcations. The bifurcation angles were 90, 105, 120, 135, 150 and 165 degrees
      ( degrees ). Experiment 1 was conducted to assess in what coronary bifurcation
      the reverse wire technique is required. Antegrade guidewire advancement was
      conducted with two different guidewires: the spring coil guidewire SION blue and
      the polymer-jacket hydrophilic guidewire Fielder FC. Experiment 2 was conducted
      to determine what the optimal guidewire selection and the optimal guidewire shape
      for the reverse wire technique would be. Assessment of the guidewire crossability
      into the highly angulated side branch was performed, and then the balloon
      crossability was assessed. A total of four guidewire types were compared in
      experiment 2. In experiment 1, guidewire crossing was impossible by conventional
      antegrade wiring when the bifurcation angle became 150 degrees  or more. In
      experiment 2, guidewire crossing of more than 150 degrees  of bifurcation angle
      was achievable independent of the guidewire types and shape. Balloon
      deliverability was best when using a polymer-jacket hydrophilic guidewire with a
      round shape 3 cm from the guidewire tip. CONCLUSIONS: Although the guidewire
      crossing into the side branch was impossible by conventional antegrade methods
      when the bifurcation angle became 150 degrees  or more, the guidewire crossing
      into such a highly angulated side branch was easily possible using the reverse
      wire technique. The optimal guidewire selection for the reverse wire technique is
      the polymer-jacket hydrophilic guidewire with a round shape 3 cm from the
      guidewire tip.

PMID- 24280161
TI  - Pre-defining optimal C-arm position for TAVI with CT-scan using free software.

PMID- 24280162
TI  - Tools & techniques clinical: optimising stenting strategy in bifurcation lesions
      with insights from in vitro bifurcation models.

PMID- 24280163
TI  - Complex bifurcation percutaneous coronary intervention with the Absorb
      bioresorbable vascular scaffold.

PMID- 24280164
TI  - Co-registration of fractional flow reserve and optical coherence tomography with
      the use of a three-dimensional angiographic roadmap: an opportunity for
      optimisation of complex percutaneous coronary interventions.

PMID- 24280165
TI  - Childhood dietary patterns and later obesity: a review of the evidence.
AB  - A range of individual nutrients and foods have been suggested to increase obesity
      risk in childhood, but the evidence is inconsistent. Dietary patterns that
      summarise the whole diet may, however, be more informative. The aim of the
      present paper was to systematically review the current evidence pertaining to
      overall dietary patterns in childhood and later obesity risk. Studies eligible
      for review identified childhood dietary patterns using an empirical method, i.e.
      principal components analysis, factor analysis or reduced rank regression, and
      reported their prospective associations with an obesity-related outcome.
      Literature searches identified 166 studies and of these, seven met the
      eligibility criteria. Despite differences between studies, a common dietary
      pattern was identified in all seven studies that was high in energy-dense, high
      fat and low-fibre foods. The quality of studies varied, however; the four studies
      reporting positive associations between this type of dietary pattern and later
      obesity risk were of consistently higher quality than those reporting null
      associations. The balance of evidence from this systematic review indicates that
      dietary patterns that are high in energy-dense, high-fat and low-fibre foods
      predispose young people to later overweight and obesity. It also highlights that
      examining multiple dietary factors within a dietary pattern may better explain
      obesity risk than individual nutrients or foods. However, more prospective
      studies are needed and dietary pattern research requires greater rigour and
      focus, to further clarify the role of dietary factors in the aetiology of obesity
      and inform future interventions. 

PMID- 24280166
TI  - A comparison of ballet dancers with different level of experience in performing
      single-leg stance on retire position.
AB  - The purpose of the current study was to evaluate the postural stability of single
      leg standing on the retire position in ballet dancers having three different
      levels of skill. Nine superior experienced female ballet dancers, 9 experienced,
      and 12 novice dancers performed single-leg standing in the retire position. The
      parameters of center of pressure (COP) in the anterior-posterior and medial
      lateral directions and the maximum distance between COP and the center of mass
      (COM) were measured. The inclination angles of body segments (head, torso, and
      supporting leg) in the frontal plane were also calculated. The findings showed
      that the novice dancers had a trend of greater torso inclination angles than the
      experienced dancers but that the superior experienced dancers had greater maximum
      COM-COP distance in the anterior-posterior direction. Furthermore, both
      experienced and novice dancers had better balance when standing on the
      nondominant leg, whereas the superior experienced dancers had similar postural
      stability between legs. Based on the findings, ballet training should put equal
      focus on both legs and frontal plane control (medial-lateral direction) should be
      integrated to ballet training program. 

PMID- 24280168
TI  - An insight into plant lipase research - challenges encountered.
AB  - Lipases from bacterial, fungal, and animal sources have been purified to
      homogeneity with very few of them being contributed from plants. Plant lipases
      are mostly found in energy reserve tissues, for example, oilseeds. They act as
      biocatalysts which are attractive due to their high substrate specificity, low
      production cost and easy pharmacological acceptance due to their eukaryotic
      origin. Hence plant lipases represent better potential for commercial
      applications in organic synthesis, food, detergent and pharmacological
      industries. However, low expression, uneconomical fold purity and the plethora of
      difficulties related to their recombinant expression has been limiting their
      commercial applicability and posing challenges to many researchers. This article
      focuses on comprehensive approaches that have been reported to date to address
      these challenges. 

PMID- 24280167
TI  - Calorie restriction and cancer prevention: a mechanistic perspective.
AB  - Calorie restriction (CR) is one of the most potent broadly acting dietary
      interventions for inducing weight loss and for inhibiting cancer in experimental
      models. Translation of the mechanistic lessons learned from research on CR to
      cancer prevention strategies in human beings is important given the high
      prevalence of excess energy intake, obesity, and metabolic syndrome in many parts
      of the world and the established links between obesity-associated metabolic
      perturbations and increased risk or progression of many types of cancer. This
      review synthesizes findings on the biological mechanisms underlying many of the
      anticancer effects of CR, with emphasis on the impact of CR on growth factor
      signaling pathways, inflammation, cellular and systemic energy homeostasis
      pathways, vascular perturbations, and the tumor microenvironment. These CR
      responsive pathways and processes represent targets for translating CR research
      into effective cancer prevention strategies in human beings. 

PMID- 24280169
TI  - Biomechanical evaluation of magnesium-based resorbable metallic screw system in a
      bilateral sagittal split ramus osteotomy model using three-dimensional finite
      element analysis.
AB  - PURPOSE: The aim of this study was to evaluate the stress distribution of a
      magnesium (Mg)-based resorbable screw system in a bilateral sagittal split ramus
      osteotomy (BSSO) and to compare its biomechanical stability with those of
      titanium (Ti)-based and polymer (IN)-based systems. MATERIALS AND METHODS: A 3
      dimensional BSSO model (10-mm advancement and setback) was constructed with
      Mimics. Bicortical screw fixation using Ti, IN, and Mg screws was performed with
      4 different geometries of fixation. With an occlusal load of 132 N on the lower
      first molar, the von Mises stress (VMS) distribution was calculated using ANSYS.
      RESULTS: The VMS distribution of Mg was more similar to that of Ti than to that
      of IN. In all cases, the highest VMS was concentrated on the screw at the most
      posterior and superior area. Stress was distributed mainly around the screw holes
      (cancellous bone) and the retromolar area (cortical bone). In the advancement
      surgery, fixation with 5 Mg screws (5A-Mg, 99.810 MPa at cortical bone) showed
      biomechanical stability, whereas fixation with the same number of IN screws did
      not (5A-IN, 109.021 MPa at cortical bone). In the setback surgery, although the
      maximum VMSs at cortical bone for Mg, IN, and Ti were lower than 108 MPa (yield
      strength of cortical bone), Mg screws showed more favorable results than IN
      screws because the maximum VMSs of Mg at cancellous bone were lower than those of
      IN. CONCLUSION: The Mg-based resorbable screw system is a promising alternative
      to the IN-based system.

PMID- 24280170
TI  - Total mandibular subapical osteotomy and Le Fort I osteotomy using piezosurgery
      and computer-aided designed and manufactured surgical splints: a favorable
      combination of three techniques in the management of severe mouth asymmetry in
      Parry-Romberg syndrome.
AB  - Although its pathogenesis remains obscure, Parry-Romberg syndrome (PRS) has been
      associated with the linear scleroderma en coup de sabre. PRS is characterized by
      unilateral facial atrophy of the skin, subcutaneous tissue, muscles, and bones
      with at least 1 dermatome supplied by the trigeminal nerve. Facial asymmetry
      represents the most common sequela and can involve the soft tissues,
      craniomaxillofacial skeleton, dentoalveolar area, and temporomandibular joint.
      Although orthognathic procedures have been reported for skeletal reconstruction,
      treatment of facial asymmetry has been directed to augmentation of the soft
      tissue volume on the atrophic side using different recontouring or volumetric
      augmentation techniques. Total mandibular subapical osteotomy has been used in
      the management of dentofacial deformities, such as open bite and mandibular
      dentoalveolar retrusion or protrusion associated with an imbalance between the
      lower lip and the chin. Management of orthognathic procedures has been improved
      by the recent introduction of stereolithographic surgical splints using computer
      aided design (CAD) and computer-aided manufacturing (CAM) technology and
      piezosurgery. Piezosurgery has increased security during surgery, especially for
      delicate procedures associated with a high risk of nerve injury. The present
      report describes a combined total mandibular subapical osteotomy and Le Fort I
      osteotomy using piezosurgery and surgical splints fabricated using CAD and CAM
      for the correction of severe mouth asymmetry related to vertical dentoalveolar
      disharmony in a patient with PRS. 

PMID- 24280171
TI  - Mandibular condylectomy revisited: technical notes concerning the use of an
      ultrasonic system.
AB  - Condylar hyperplasia is a well-known pathologic entity with an established
      treatment protocol. Traditionally, saws and drills have been used in the condylar
      osteotomy. The use of ultrasonic systems has optimized many procedures in the
      maxillofacial area; however, exploration of the use of this technique for
      condylectomy has been limited. Ultrasonic systems offer several advantages, such
      as a decrease in the risk of blood vessel damage and clarity of the osteotomy.
      The present report addressed the scope of condylar osteotomy using ultrasonic
      systems. 

PMID- 24280172
TI  - Le Fort III distraction osteogenesis versus conventional Le Fort III osteotomy in
      correction of syndromic midfacial hypoplasia: a systematic review.
AB  - PURPOSE: It has been debated whether the Le Fort III procedure using distraction
      osteogenesis (LFIII-DO) reduces the risk of postintervention relapse compared
      with conventional Le Fort III (LFIII) osteotomy in the correction of syndromic
      midfacial hypoplasia. Our objective was to evaluate the short- and long-term
      stability of the bony structures after midfacial advancement using conventional
      LFIII osteotomy versus LFIII-DO in patients with syndromic midfacial hypoplasia.
      MATERIALS AND METHODS: We performed a systematic review of the published data. An
      electronic search of 10 databases was performed from their inception through June
      2012. The reference lists of the relevant publications were also reviewed.
      Studies were considered for inclusion if they were longitudinal clinical studies
      with follow-up periods of at least 1 year after surgery (LFIII group) or at the
      end of the consolidation period (LFIII-DO group). Study selection, risk of bias
      assessment, and data extraction were performed in duplicate. The methodologic and
      clinical heterogeneity across the studies precluded combining the findings using
      meta-analyses. RESULTS: A total of 57 reports met the initial search criteria,
      and 12 reports were finally selected. The studies demonstrated a mean midfacial
      advancement of 8 to 12 mm in the LFIII group and 9 to 16 mm in the LFIII-DO
      group. For the LFIII group, horizontal short-term follow-up showed a maximal rate
      of relapse of 8.7 to 11.9% in 2 studies, with 1 study demonstrating a far more
      severe rate of maximal relapse of 50%. For the LFIII-DO procedure, the horizontal
      short-term relapse rate was 14.4% in 1 study, with the remainder demonstrating a
      rate of relapse of less than 10%. Moreover, 3 studies even showed additional
      advancement without any rate of relapse. CONCLUSIONS: Current evidence suggests
      that conventional LFIII and LFIII-DO techniques can effectively advance the
      midface forward in patients with syndromic midfacial hypoplasia and have good to
      excellent stability, with a mild rate of relapse. However, the LFIII-DO technique
      appears to achieve a greater amount of advancement with a lower rate of relapse
      compared with the conventional LFIII technique.

PMID- 24280173
TI  - Letter to the editor.

PMID- 24280174
TI  - Cherubism: a case report of a three-generation inheritance and literature review.
AB  - Cherubism is a rare, non-neoplastic pathologic entity first described by Jones in
      1933. It affects mostly younger individuals and is usually inherited. Cherubism
      presents as a painless jaw enlargement that affects both the maxilla and the
      mandible and is characterized by replacement of the osseous tissue by fibrous
      connective tissue. Radiologically, the lesions appear as multiple, multilocular
      radiolucent spaces with distinct borders divided by bony septations, which often
      dramatically alter the shape and size of the jaw structures. These often result
      in marked facial abnormalities. Cervical lymphadenopathy is not uncommon in those
      affected. The disease is self-limited and can reverse itself with time.
      Approximately 250 cases have been reported in published studies, mostly affecting
      males. The purpose of our report was to present a case of cherubism diagnosed in
      a young girl and the long-term (3 generations) follow-up evaluation of her mother
      and grandmother, both of whom had been diagnosed with the same pathologic entity.

PMID- 24280175
TI  - Le Fort IV + I distraction osteogenesis using an internal device for syndromic
      craniosynostosis.
AB  - Monobloc and Le Fort III distractions can improve midfacial hypoplasia, a
      characteristic feature of syndromic craniosynostosis. The purpose of treating
      midfacial hypoplasia is to improve exophthalmos and dental occlusion. Typically,
      in Le Fort III or monobloc distractions, the midface is mobilized en bloc, and
      the extent and direction of the mobilization is determined according to the
      preferred intermaxillary occlusion. However, to obtain the preferred functional
      and esthetic results while correcting midface hypoplasia, the most sensible
      approach is the use of different degrees of mobilization and vectors for the
      upper and lower halves of the midface. This report describes the case of an
      adolescent with Crouzon syndrome showing frontal recession exophthalmos and an
      anterior crossbite. His condition was treated with monobloc minus Le Fort I and
      Le Fort I distraction using only internal devices, which the authors have
      designated Le Fort IV plus I distraction. 

PMID- 24280176
TI  - Vena cava filters in unstable elderly patients with acute pulmonary embolism.
AB  - BACKGROUND: Inferior vena cava filters are associated with a reduced in-hospital
      all-cause case fatality rate of unstable patients with acute pulmonary embolism.
      Whether vena cava filters are associated with a reduced case fatality rate in
      adults of all ages with unstable pulmonary embolism, particularly the elderly,
      has not been determined. METHODS: Unstable patients with pulmonary embolism (in
      shock or ventilator dependent) 1999-2008 were identified from the Nationwide
      Inpatient Sample. RESULTS: Among 21,095 unstable patients with pulmonary embolism
      who received thrombolytic therapy, in-hospital all-cause case fatality rate was
      lower in every age group who received a vena cava filter in addition to
      thrombolytic therapy (P = .0012 to <.0001). Patients aged >= 81 years showed the
      greatest absolute reduction of case fatality rate with filters (19.3%). Among
      50,210 unstable patients who did not receive thrombolytic therapy, case fatality
      rate also was lower in every age group who received a vena cava filter (all P
      <.0001). Patients aged >= 81 years with vena cava filters showed the greatest
      absolute risk reduction of case fatality rate (27.7%). CONCLUSION: Vena cava
      filters are associated with a reduced in-hospital all-cause case fatality rate in
      unstable adults with pulmonary embolism, irrespective of age.

PMID- 24280177
TI  - Leadership in health care for the 21st century: challenges and opportunities.

PMID- 24280178
TI  - [Award for best original research article published in Archivos de Cardiologia de
      Mexico in 2012].

PMID- 24280179
TI  - [Medical significance of endothelial glycocalyx].
AB  - Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans
      and glycoproteins attached to the vascular endothelial luminal surface. It has
      several physiological roles: shear stress mechanotransduction to the endothelial
      cells, regulation of fluids and macromolecules vascular permeability, of
      coagulation cascade activation and fibrinolysis, and protects the endothelium
      from platelets and leukocytes adhesion. In general, glycocalyx protects vascular
      wall against pathogenic insults. The glycocalyx may be damaged by abnormal shear
      stress, reactive oxygen species, hypernatremia, hyperglycemia,
      hypercholesterolemia and inflammatory molecules, resulting in endothelial
      dysfunction, enhanced vascular permeability, lipoproteins leakage to
      subendothelial space, activation of plasma coagulation, and increased adherence
      of platelets and leukocytes to the endothelial cells. Shredding of glycocalyx
      appears as an important initial step in the pathophysiology of vascular diseases.

PMID- 24280180
TI  - p53 promotes the expression of gluconeogenesis-related genes and enhances hepatic
      glucose production.
AB  - BACKGROUND: The p53 tumor suppressor protein is a transcription factor that
      initiates transcriptional programs aimed at inhibiting carcinogenesis. p53
      represses metabolic pathways that support tumor development (such as glycolysis
      and the pentose phosphate pathway (PPP)) and enhances metabolic pathways that are
      considered counter-tumorigenic such as fatty acid oxidation. FINDINGS: In an
      attempt to comprehensively define metabolic pathways regulated by p53, we
      performed two consecutive high-throughput analyses in human liver-derived cells
      with varying p53 statuses. A gene expression microarray screen followed by
      constraint-based modeling (CBM) predicting metabolic changes imposed by the
      transcriptomic changes suggested a role for p53 in enhancing gluconeogenesis (de
      novo synthesis of glucose). Examining glucogenic gene expression revealed a p53
      dependent induction of genes involved in both gluconeogenesis (G6PC, PCK2) and in
      supplying glucogenic precursors (glycerol kinase (GK), aquaporin 3 (AQP3),
      aquaporin 9 (AQP9) and glutamic-oxaloacetic transaminase 1 (GOT1)). Accordingly,
      p53 augmented hepatic glucose production (HGP) in both human liver cells and
      primary mouse hepatocytes. CONCLUSIONS: These findings portray p53 as a novel
      regulator of glucose production. By facilitating glucose export, p53 may prevent
      it from being shunted to pro-cancerous pathways such as glycolysis and the PPP.
      Thus, our findings suggest a metabolic pathway through which p53 may inhibit
      tumorigenesis.

PMID- 24280181
TI  - Reduced salience and default mode network activity in women with anorexia
      nervosa.
AB  - BACKGROUND: The neurobiology of anorexia nervosa is poorly understood. Neuronal
      networks contributing to action selection, self-regulation and interoception
      could contribute to pathologic eating and body perception in people with anorexia
      nervosa. We tested the hypothesis that the salience network (SN) and default mode
      network (DMN) would show decreased intrinsic activity in women with anorexia
      nervosa and those who had recovered from the disease compared to controls. The
      basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated.
      METHODS: Between January 2008 and January 2012, women with restricting-type
      anorexia nervosa, women who recovered from the disease and healthy control women
      completed functional magnetic resonance imaging during a conditioned stimulus
      task. Network activity was studied using independent component analysis. RESULTS:
      We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls.
      Salience network activity in the anterior cingulate cortex was reduced in women
      with anorexia nervosa (p = 0.030; all results false-discovery rate- corrected)
      and recovered women (p = 0.039) compared to controls. Default mode network
      activity in the precuneus was reduced in women with anorexia compared to controls
      (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA;
      p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was
      reduced in women with anorexia compared to controls; SMN activity in the SMA (p =
      0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with
      anorexia compared to recovered women. There were no group differences in the BGN.
      LIMITATIONS: Differences between patient and control populations (e.g.,
      depression, anxiety, medication) are potential confounds, but were included as
      covariates. CONCLUSION: Reduced SN activity in women with anorexia nervosa and
      recovered women could be a trait-related biomarker or illness remnant, altering
      the drive to approach food. The alterations in the DMN and SMN observed only in
      women with anorexia nervosa suggest state-dependent abnormalities that could be
      related to altered interoception and body image in these women when they are
      underweight but that remit following recovery.

PMID- 24280182
TI  - Possible role of more positive social behaviour in the clinical effect of
      antidepressant drugs.
AB  - Increasing serotonin decreases quarrelsome behaviours and enhances agreeable
      behaviours in humans. Antidepressants, even those whose primary action is not on
      serotonin, seem to increase serotonin function. We suggest that antidepressants
      act in part by effects on social behaviour, which leads to a gradual improvement
      in mood. We review the evidence supporting the idea that antidepressants may be
      moving behaviour from quarrelsome to agreeable. The more positive social
      responses of interaction partners would initiate a cycle of more positive social
      behaviour, and this iterative process would result in a clinically significant
      improvement in mood. 

PMID- 24280183
TI  - Multi-parent advanced generation inter-cross (MAGIC) populations in rice:
      progress and potential for genetics research and breeding.
AB  - BACKGROUND: This article describes the development of Multi-parent Advanced
      Generation Inter-Cross populations (MAGIC) in rice and discusses potential
      applications for mapping quantitative trait loci (QTLs) and for rice varietal
      development. We have developed 4 multi-parent populations: indica MAGIC (8 indica
      parents); MAGIC plus (8 indica parents with two additional rounds of 8-way F1
      inter-crossing); japonica MAGIC (8 japonica parents); and Global MAGIC (16
      parents - 8 indica and 8 japonica). The parents used in creating these
      populations are improved varieties with desirable traits for biotic and abiotic
      stress tolerance, yield, and grain quality. The purpose is to fine map QTLs for
      multiple traits and to directly and indirectly use the highly recombined lines in
      breeding programs. These MAGIC populations provide a useful germplasm resource
      with diverse allelic combinations to be exploited by the rice community. RESULTS:
      The indica MAGIC population is the most advanced of the MAGIC populations
      developed thus far and comprises 1328 lines produced by single seed descent
      (SSD). At the S4 stage of SSD a subset (200 lines) of this population was
      genotyped using a genotyping-by-sequencing (GBS) approach and was phenotyped for
      multiple traits, including: blast and bacterial blight resistance, salinity and
      submergence tolerance, and grain quality. Genome-wide association mapping
      identified several known major genes and QTLs including Sub1 associated with
      submergence tolerance and Xa4 and xa5 associated with resistance to bacterial
      blight. Moreover, the genome-wide association study (GWAS) results also
      identified potentially novel loci associated with essential traits for rice
      improvement. CONCLUSION: The MAGIC populations serve a dual purpose: permanent
      mapping populations for precise QTL mapping and for direct and indirect use in
      variety development. Unlike a set of naturally diverse germplasm, this population
      is tailor-made for breeders with a combination of useful traits derived from
      multiple elite breeding lines. The MAGIC populations also present opportunities
      for studying the interactions of genome introgressions and chromosomal
      recombination.

PMID- 24280184
TI  - Twenty-year experience with the CarboMedics mechanical valve prosthesis.
AB  - BACKGROUND: The CarboMedics mechanical prosthesis (CarboMedics Inc, Austin, TX)
      has been used for mitral and aortic valve replacement for more than 20 years in
      our institution. This study describes the long-term survival of patients with
      this prosthesis as well as the valve-related events. METHODS: Between June 1988
      and May 2010, 3,297 patients underwent either single aortic valve replacement
      (AVR) (2,242 patients) or mitral valve replacement (MVR) (1,055 patients) with
      the CarboMedics mechanical valve prosthesis. They were followed annually for
      valve-related complications at the Montreal Heart Institute valve clinic.
      RESULTS: Operative mortality was 4% with AVR and 7% with MVR. Total follow-up was
      23,671 patient-years (range, 1 month to 21 years; average, 7.5 +/- 5.3 years). At
      20 years, patient freedom from late mortality was 43.2% in the AVR group and
      40.9% in the MVR group. Freedom from valve-related mortality was 78.3% for AVR
      and 74.6% for MVR. Freedom from thromboembolic event was 91.6% for AVR and 88.5%
      for MVR. Freedom from reoperation was 89.2% for AVR and 80.3% for MVR. Freedom
      from bleeding event was 89.5% for AVR and 88% for MVR. Freedom from endocarditis
      was 97.3% for both AVR and MVR. Freedom from valve thrombosis was 98.9% for AVR
      and 91.4% for MVR. There was no structural valve failure in our cohort.
      CONCLUSIONS: The CarboMedics valve is an effective and durable mechanical valve
      prosthesis with a low event rate and no structural failure at 20 years.

PMID- 24280185
TI  - Discharge outcomes in patients with paracorporeal biventricular assist devices.
AB  - BACKGROUND: As waiting time for heart transplantation has increased, ventricular
      assist devices have become critical for "bridging" patients with end-stage heart
      failure. Because most reported post-discharge experience is with left ventricular
      assist devices (LVAD), we sought to evaluate the safety and feasibility of home
      discharge on paracorporeal biventricular assist devices (BIVAD). METHODS: We
      retrospectively reviewed the hospital course and post-discharge outcomes of 46
      consecutive patients who received paracorporeal VADs as bridge to transplant. The
      success of home discharge was assessed by frequency and reasons for hospital
      readmission and survival to transplant. RESULTS: Thirty patients (65%) were
      successfully transferred from the intensive care unit and considered candidates
      for discharge. Of the 26 patients discharged home, 11 were supported with an LVAD
      and 15 with BIVADs. Median duration of support until transplant, explant, or
      death did not differ significantly between LVAD or BIVAD patients (91 days vs 158
      days; p = 0.09). There were 26 readmissions for medical or device-related
      complications; 10 in 7 LVAD patients and 16 in 10 BIVAD patients, with no
      difference in median length of stay (17 days vs 25 days; p = 0.67). Out of
      hospital duration of support was similar between LVAD and BIVAD patients (61 days
      vs 66 days; p = 0.87) as were 6-month and 1-year event-free survival rates (p =
      0.49). CONCLUSIONS: Outcomes were similar in patients bridged to transplant on
      home paracorporeal BIVAD versus LVAD support. We recommend discharge for stable
      patients demonstrating device competency and adequate home care regardless of the
      need for univentricular or biventricular paracorporeal support.

PMID- 24280186
TI  - A novel rigid annuloplasty ring for aortic valve reconstruction: an in vitro
      investigation.
AB  - BACKGROUND: Remodeling of the dilated valve annulus with a prosthetic ring for
      repair of valve insufficiency is a well-established concept in mitral and
      tricuspid valve surgery and may also be suitable for aortic valve reconstruction.
      A novel rigid aortic annuloplasty ring was tested in vitro. METHODS: Ten fresh
      porcine aortic roots were investigated in a pulsatile flow simulator before
      surgery (group N), after patch dilatation of the annulus (group D), and after
      reconstruction using a rigid annuloplasty ring (group R). The ring was designed
      to (1) prevent contact with the leaflets, reducing the risk of contact injury,
      (2) be applicable to all valve phenotypes, (3) prevent injury to the conduction
      bundle, and (4) be implantable from inside the aortic root (subvalvular). For
      each group pressure gradient, leakage volume, and coaptation height were
      measured. RESULTS: With the annuloplasty ring, regurgitation volume decreased
      from -8.50 +/- 1.91 mL (group D) to -4.75 +/- 1.66 mL (group R; p < 0.0003), not
      different from group N. Coaptation height of the leaflets increased from 0.62 +/-
      0.08 mm (group D) to 0.77 +/- 0.11 mm (group R; p < 0.005), similar to group N.
      Mean pressure gradient increased from 2.98 +/- 0.38 mm Hg (group D) to 3.72 +/-
      0.40 mm Hg (group R; p < 0.0001). CONCLUSIONS: This novel aortic annuloplasty
      ring has the potential for supporting aortic valve reconstruction by remodeling
      the subvalvular area.

PMID- 24280187
TI  - Evidence-based lifestyle interventions in the workplace--an overview.
AB  - BACKGROUND: Lifestyle-related health issues affect the economic position of
      organizations and contribute to reduced productivity, increased absenteeism and
      health care costs. AIMS: To summarize the effectiveness of different workplace
      health interventions for promoting healthy lifestyle, preventing diseases and
      reducing health care costs. METHODS: We searched MEDLINE via Pubmed, EMBASE,
      Cochrane Library, NelH, HighWire Press and Google Scholar in March 2012.
      Systematic reviews and meta-analyses of workplace interventions aimed at
      promoting physical activity, healthy weight and good nutrition were included.
      Three authors assessed the quality of the reviews and extracted data on methods,
      interventions, outcomes, results and effect sizes. RESULTS: We identified 15
      publications covering a total of 379 original studies. Three systematic reviews
      found beneficial effects of workplace nutrition interventions on employees'
      dietary behaviour. Three reviews found multi-component physical activity
      interventions to be effective in increasing employees' physical activity and
      fitness. The other activity promotion interventions were less effective regarding
      physical activity and weight-related outcomes. In terms of weight management, our
      findings favour multi-component interventions that focus on both physical
      activity and nutrition over single dietary programmes. CONCLUSIONS: Workplace
      health promotion interventions may improve physical activity, dietary behaviour
      and healthy weight. There is no evidence of increased efficacy associated with
      specific intervention types. Workplace health promotion should focus on either
      physical activity or weight or nutrition behaviour to maximize effectiveness.
      Best evidence is available for multi-component interventions.

PMID- 24280188
TI  - Enhancing provider knowledge and patient screening for palliative care needs in
      chronic multimorbid patients receiving home-based primary care.
AB  - This article describes a pilot model to increase palliative care (PC) knowledge
      and collaboration among providers and to systematically identify chronic
      multimorbid home care patients who would benefit from focused discussion of
      potential PC needs. Thirty health care providers from a home-based primary care
      team attended interdisciplinary trainings. The Palliative Performance Scale (PPS)
      tool was used to trigger discussions of potential palliative needs at team rounds
      for patients who scored below a cutoff point on the tool. Palliative Performance
      Scale implementation added little burden on nurses and triggered a discussion in
      51 flagged patients. The tool successfully identified 75% of patients who died or
      were discharged. Screening was systematic and consistent and resulted in targeted
      discussions about PC needs without generating additional burden on our PC consult
      service. This model shows promise for enhancing collaborative patient care and
      access to PC. 

PMID- 24280189
TI  - Conservation and utilization of African Oryza genetic resources.
AB  - Africa contains a huge diversity of both cultivated and wild rice species. The
      region has eight species representing six of the ten known genome types. Genetic
      resources of these species are conserved in various global germplasm repositories
      but they remain under collected and hence underrepresented in germplasm
      collections. Moreover, they are under characterized and therefore grossly
      underutilized. The lack of in situ conservation programs further exposes them to
      possible genetic erosion or extinction. In order to obtain maximum benefits from
      these resources, it is imperative that they are collected, efficiently conserved
      and optimally utilized. High throughput molecular approaches such as genome
      sequencing could be employed to more precisely study their genetic diversity and
      value and thereby enhance their use in rice improvement. Oryza sativa was the
      first crop plant to have its reference genome sequence released marking a major
      milestone that opened numerous opportunities for functional characterization of
      the entire rice genome. Studies have however demonstrated that one reference
      genome sequence is not enough to fully explore the genetic variation in the Oryza
      genus, hence the need to have reference sequences for other species in the genus.
      An overview of the state of conservation and utilization of African Oryza is
      hereby presented. Progress in the release of reference genome sequences for these
      species is also highlighted. 

PMID- 24280191
TI  - White matter microstructural abnormalities in families multiply affected with
      bipolar I disorder: a diffusion tensor tractography study.
AB  - BACKGROUND: White matter (WM) abnormalities are proposed as potential
      endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging
      (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we
      previously reported that widespread abnormalities of fractional anisotropy (FA)
      are associated with both BD and genetic liability for illness. In the present
      study, we further investigated the endophenotypic potential of WM abnormalities
      by applying DTI tractography to specifically investigate tracts implicated in the
      pathophysiology of BD. METHOD: Diffusion magnetic resonance imaging (MRI) data
      were acquired from 19 patients with BD type I from multiply affected families, 21
      of their unaffected first-degree relatives and 18 healthy volunteers. DTI
      tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate
      portion of the superior longitudinal fasciculus (SLF), inferior longitudinal
      fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule
      (ALIC). Regression analyses were conducted to investigate the effect of
      participant group and genetic liability on FA and radial diffusivity (RD) in each
      tract. RESULTS: We detected a significant effect of group on both FA and RD in
      the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased
      RD in patients compared to controls and relatives. Increasing genetic liability
      was associated with decreased FA and increased RD in the UF, and decreased FA in
      the SLF, among patients. CONCLUSIONS: WM microstructural abnormalities in limbic,
      temporal and callosal pathways represent microstructural abnormalities associated
      with BD whereas alterations in the SLF and UF may represent potential markers of
      endophenotypic risk.

PMID- 24280190
TI  - Respiratory complex I is essential to induce a Warburg profile in mitochondria
      defective tumor cells.
AB  - BACKGROUND: Aerobic glycolysis, namely the Warburg effect, is the main hallmark
      of cancer cells. Mitochondrial respiratory dysfunction has been proposed to be
      one of the major causes for such glycolytic shift. This hypothesis has been
      revisited as tumors appear to undergo waves of gene regulation during
      progression, some of which rely on functional mitochondria. In this framework,
      the role of mitochondrial complex I is still debated, in particular with respect
      to the effect of mitochondrial DNA mutations in cancer metabolism. The aim of
      this work is to provide the proof of concept that functional complex I is
      necessary to sustain tumor progression. METHODS: Complex I-null osteosarcoma
      cells were complemented with allotopically expressed complex I subunit 1 (MT
      ND1). Complex I re-assembly and function recovery, also in terms of NADH
      consumption, were assessed. Clones were tested for their ability to grow in soft
      agar and to generate tumor masses in nude mice. Hypoxia levels were evaluated via
      pimonidazole staining and hypoxia-inducible factor-1alpha (HIF-1alpha)
      immunoblotting and histochemical staining. 454-pyrosequencing was implemented to
      obtain global transcriptomic profiling of allotopic and non-allotopic xenografts.
      RESULTS: Complementation of a truncative mutation in the gene encoding MT-ND1,
      showed that a functional enzyme was required to perform the glycolytic shift
      during the hypoxia response and to induce a Warburg profile in vitro and in vivo,
      fostering cancer progression. Such trigger was mediated by HIF-1alpha, whose
      stabilization was regulated after recovery of the balance between alpha
      ketoglutarate and succinate due to a recuperation of NADH consumption that
      followed complex I rescue. CONCLUSION: Respiratory complex I is essential for the
      induction of Warburg effect and adaptation to hypoxia of cancer cells, allowing
      them to sustain tumor growth. Differently from other mitochondrial tumor
      suppressor genes, therefore, a complex I severe mutation such as the one here
      reported may confer anti-tumorigenic properties, highlighting the prognostic
      values of such genetic markers in cancer.

PMID- 24280192
TI  - MSC-based VEGF gene therapy in rat myocardial infarction model using facial
      amphipathic bile acid-conjugated polyethyleneimine.
AB  - Mesenchymal stem cells (MSCs) have attracted much attention in regenerative
      medicine owing to their apparent usefulness as multi-potent replacement cells.
      The potential of MSC therapy can be further improved by transforming MSCs with
      therapeutic genes that maximize the efficacy of gene therapy and their own
      therapeutic ability. Since most conventional transfection methodologies have
      shown marginal success in delivering exogenous genes into primary cultured cells,
      efficient gene transfer into primary MSCs is a prerequisite for the development
      of MSC-based gene therapy strategies to achieve repair and regeneration of
      damaged tissues. Herein, facially amphipathic bile acid-modified
      polyethyleneimine (BA-PEI) conjugates were synthesized and used to transfer
      hypoxia-inducible vascular endothelial growth factor gene (pHI-VEGF) in MSCs for
      the treatment of rat myocardial infarction. Under the optimized transfection
      conditions, the BA-PEI conjugates significantly increased the VEGF protein
      expression levels in rat MSCs, compared with traditional transfection methods
      such as LipofectamineTM and branched-PEI (25 kDa). Furthermore, the prepared pHI
      VEGF-engineered MSCs (VEGF-MSCs) resulted in improved cell viability,
      particularly during severe hypoxic exposure in vitro. The transplantation of MSCs
      genetically modified to overexpress VEGF by BA-PEI enhanced the capillary
      formation in the infarction region and eventually attenuated left ventricular
      remodeling after myocardial infarction in rats. This study demonstrates the
      applicability of the BA-PEI conjugates for the efficient transfection of
      therapeutic genes into MSCs and the feasibility of using the genetically
      engineered MSCs in regenerative medicine for myocardial infarction.

PMID- 24280193
TI  - Assessment of five soil DNA extraction methods and a rapid laboratory-developed
      method for quality soil DNA extraction for 16S rDNA-based amplification and
      library construction.
AB  - Extraction of DNA from soil samples using standard methods often results in low
      yield and poor quality making them unsuitable for community analysis through
      polymerase chain reaction (PCR) due to the formation of chimeric products with
      smaller template DNAs and the presence of humic substances. The present study
      focused on the assessment of five different methods for metagenomic DNA isolation
      from soil samples on the basis of processing time, purity, DNA yield, suitability
      for PCR, restriction digestion and mDNA library construction. A simple and rapid
      alkali lysis based on indirect DNA extraction from soil was developed which could
      remove 90% of humic substances without shearing the DNA and permits the rapid and
      efficient isolation of high quality DNA without the requirement of
      hexadecyltrimethylammonium bromide and phenol cleanup. The size of DNA fragment
      in the crude extracts was >23 kb and yield 0.5-5 MUg/g of soil. mDNA purification
      using Sephadex G-50 resin yielded high concentration of DNA from soil samples,
      which has been successfully used for 16S rDNA based amplification of a 1500 bp
      DNA fragment with 27F and 1492R universal primers followed by restriction
      digestion and mDNA library construction.

PMID- 24280194
TI  - 1,6-Diphenyl-1,3,5-hexatrine as a reporter of inner spore membrane fluidity in
      Bacillus subtilis and Alicyclobacillus acidoterrestris.
AB  - A method to determine the inner membrane fluidity of spore populations was
      developed using the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene (DPH). DPH
      incorporated into the inner spore membrane of Bacillus subtilis ATCC 6633 and
      Alicyclobacillus acidoterrestris N1100, during static and dynamic fluidity
      experiments. The membrane fluidity of A. acidoterrestris spores stripped of the
      outer spore coats was the same as that of native spores. In addition, laser
      scanning confocal microscopy confirmed the presence of DPH in the spore membrane.
      This is the first report of spores containing fluid regions of their inner
      membranes. 

PMID- 24280195
TI  - Repetitive non-reentrant ventriculoatrial synchrony: a rare cause of
      overestimating atrial fibrillation burden.

PMID- 24280197
TI  - List of images.

PMID- 24280196
TI  - The presence of extensive atrial scars hinders the differential diagnosis of
      focal or macroreentrant atrial tachycardias in patients with complex congenital
      heart disease.
AB  - AIMS: Atrial tachycardias (ATs) frequently develop in patients with congenital
      heart defects (CHDs). This study aimed to evaluate the effects of extensive
      atrial scar formation on the total atrial activation time (TAAT) and its relation
      to the tachycardia cycle length (CL) to classify AT. METHODS AND RESULTS: Seventy
      one patients were included and divided into two groups: patients without CHD
      (Group I, 35 patients) and with CHD (Group II, 36 patients). All patients
      underwent CARTO electroanatomical activation mapping. Two subgroups were created:
      centrifugal (CAT) or macroreentrant AT (MRAT). Total atrial activation time, CL,
      and mean bipolar signal amplitude (BiSA) were analysed. In Group I, 18 patients
      (51.4%) had CAT and 17 (48.6%) MRAT. The mean BiSA for Group I was 1.30 +/- 0.32
      mV. Total atrial activation time/CL ratios were different between CAT and MRAT
      (28.4 +/- 16.9 vs. 66.6 +/- 14.3%, P < 0.001). In Group II, 18 patients (50%) had
      CAT and 18 patients (50%) MRAT. The mean BiSA was 0.94 +/- 0.50 mV and was not
      different for CAT and MRAT subgroups (1.04 +/- 0.64 vs. 0.85 +/- 0.29, P =
      0.243). Total atrial activation time/CL ratios were comparable between CAT and
      MRAT patients (69.0 +/- 40.4 vs. 83.6 +/- 8.3%, P = 0.243). A significant lower
      BiSA was found for CAT with TAAT/CL ratios above 40% (0.62 +/- 0.11 vs. 1.90 +/-
      0.18 mV, P < 0.001). A strong negative correlation was identified between the
      BiSA and the TAAT/CL ratio in patients with CAT in Group II (-0.742; P < 0.001).
      CONCLUSION: Low mean BiSA values in CHD patients are associated with altered
      impulse propagation, making TAAT- and CL-based diagnostic tools inaccurate.
      Further diagnostic tests are needed to determine the correct mechanism of ATs.

PMID- 24280199
TI  - List of illustrations.

PMID- 24280198
TI  - Introduction.

PMID- 24280201
TI  - 'Time turned solid, like a wall': four mental hospital memoirs.

PMID- 24280202
TI  - 'Will They Hear and Be Convinced by my Story?' First Person Accounts from
      Schizophrenia Bulletin.

PMID- 24280203
TI  - 'A Striking Similarity with our Theory': Freud and Bateson Read Memoirs of
      Schizophrenia.

PMID- 24280204
TI  - 'The Speech Which Arranges the Dance': The Undoing of Schizophrenia in Janet
      Frame's Autobiography and Fiction.

PMID- 24280206
TI  - 'That Damn Schizophrenia': Evolving Identity in Eunice Wood's Unwritten Story.

PMID- 24280205
TI  - Diagnostic Narrative in the DSM-IV Casebook.
AB  - On admission to the psychiatric hospital, Louise sat with her hands tightly
      clasped in her lap and avoided looking at the doctor who interviewed her. She
      answered questions readily and did not appear suspicious or guarded, but her
      affect was shallow. She denied depressed mood, delusions, or hallucinations.
      However, her answers became increasingly idiosyncratic and irrelevant as the
      interview progressed. In response to a question about her strange cooking habits,
      she replied that she did not wish to discuss recent events in Russia. When
      discussing her decline in functioning, she said, 'There's more of a take-o
      mechanism when you're younger.' Asked about ideas of reference, she said, 'I
      doubt it's true, but if one knows the writers involved, it could be an element
      that would be directed in a comical way.' Her answers were interspersed with the
      mantra, 'I'm safe. I'm safe.' 

PMID- 24280207
TI  - Bibliography.

PMID- 24280210
TI  - Inter- and intrafoot coordination when standing on balance boards.
AB  - The experiment was set up to investigate the inter- and intrafoot coordination
      dynamics of postural control on balance boards. A frequency domain principal
      component analysis (PCA) was applied on 4 center of pressure (COP) time series
      collected from two force platforms to reveal their contributions to postural
      stability. The orientation of support played a more significant role than its
      width in channeling the foot coordination dynamics. When the support was oriented
      along the AP-challenging direction, the 4 COPs revealed a parallel contribution
      to the 1st principal component (PC1) indicating an interdependence of the foot
      coordination in both directions. When the support was positioned along the ML
      challenging direction, the COPs in the AP direction showed larger weightings to
      PC1 implying an interfoot coordination. These findings provide evidence that COP
      coordination operates in adaptive ways to sustain postural stability in light of
      changing support constraints to standing. 

PMID- 24280209
TI  - Cross validation of gas chromatography-flame photometric detection and gas
      chromatography-mass spectrometry methods for measuring dialkylphosphate
      metabolites of organophosphate pesticides in human urine.
AB  - We report two analytical methods for the measurement of dialkylphosphate (DAP)
      metabolites of organophosphate pesticides in human urine. These methods were
      independently developed/modified and implemented in two separate laboratories and
      cross validated. The aim was to develop simple, cost effective, and reliable
      methods that could use available resources and sample matrices in Thailand and
      the United States. While several methods already exist, we found that direct
      application of these methods required modification of sample preparation and
      chromatographic conditions to render accurate, reliable data. The problems
      encountered with existing methods were attributable to urinary matrix
      interferences, and differences in the pH of urine samples and reagents used
      during the extraction and derivatization processes. Thus, we provide information
      on key parameters that require attention during method modification and execution
      that affect the ruggedness of the methods. The methods presented here employ gas
      chromatography (GC) coupled with either flame photometric detection (FPD) or
      electron impact ionization-mass spectrometry (EI-MS) with isotopic dilution
      quantification. The limits of detection were reported from 0.10ng/mL urine to
      2.5ng/mL urine (for GC-FPD), while the limits of quantification were reported
      from 0.25ng/mL urine to 2.5ng/mL urine (for GC-MS), for all six common DAP
      metabolites (i.e., dimethylphosphate, dimethylthiophosphate,
      dimethyldithiophosphate, diethylphosphate, diethylthiophosphate, and
      diethyldithiophosphate). Each method showed a relative recovery range of 94-119%
      (for GC-FPD) and 92-103% (for GC-MS), and relative standard deviations (RSD) of
      less than 20%. Cross-validation was performed on the same set of urine samples
      (n=46) collected from pregnant women residing in the agricultural areas of
      northern Thailand. The results from split sample analysis from both laboratories
      agreed well for each metabolite, suggesting that each method can produce
      comparable data. In addition, results from analyses of specimens from the German
      External Quality Assessment Scheme (G-EQUAS) suggested that the GC-FPD method
      produced accurate results that can be reasonably compared to other studies. 

PMID- 24280211
TI  - An evaluation of sampling effects on multiple DNA barcoding methods leads to an
      integrative approach for delimiting species: a case study of the North American
      tarantula genus Aphonopelma (Araneae, Mygalomorphae, Theraphosidae).
AB  - The North American tarantula genus Aphonopelma provides one of the greatest
      challenges to species delimitation and downstream identification in spiders
      because traditional morphological characters appear ineffective for evaluating
      limits of intra- and interspecific variation in the group. We evaluated the
      efficacy of numerous molecular-based approaches to species delimitation within
      Aphonopelma based upon the most extensive sampling of theraphosids to date, while
      also investigating the sensitivity of randomized taxon sampling on the
      reproducibility of species boundaries. Mitochondrial DNA (cytochrome c oxidase
      subunit I) sequences were sampled from 682 specimens spanning the genetic,
      taxonomic, and geographic breadth of the genus within the United States. The
      effects of random taxon sampling compared traditional Neighbor-Joining with three
      modern quantitative species delimitation approaches (ABGD, P ID(Liberal), and
      GMYC). Our findings reveal remarkable consistency and congruence across various
      approaches and sampling regimes, while highlighting highly divergent outcomes in
      GMYC. Our investigation allowed us to integrate methodologies into an efficient,
      consistent, and more effective general methodological workflow for estimating
      species boundaries within the mygalomorph spider genus Aphonopelma. Taken alone,
      these approaches are not particularly useful - especially in the absence of prior
      knowledge of the focal taxa. Only through the incorporation of multiple lines of
      evidence, employed in a hypothesis-testing framework, can the identification and
      delimitation of confident species boundaries be determined. A key point in
      studying closely related species, and perhaps one of the most important aspects
      of DNA barcoding, is to combine a sampling strategy that broadly identifies the
      extent of genetic diversity across the distributions of the species of interest
      and incorporates previous knowledge into the "species equation" (morphology,
      molecules, and natural history). 

PMID- 24280212
TI  - Decreased affinity of recombinant human tumor necrosis factor-related apoptosis
      inducing ligand (rhTRAIL) D269H/E195R to osteoprotegerin (OPG) overcomes TRAIL
      resistance mediated by the bone microenvironment.
AB  - The bone marrow microenvironment provides important signals for the survival and
      proliferation of hematopoietic and malignant cells. In multiple myeloma, plasma
      cells are surrounded by stromal cells including osteoblasts. These stromal cells
      protect multiple myeloma cells from apoptosis induced by chemotherapeutic agents.
      Osteoprotegerin (OPG), a soluble receptor of the cytokine TNF-related apoptosis
      inducing ligand (TRAIL), is secreted by osteoblasts and has been implicated in
      the prevention of cell death induced by TRAIL in malignant cells. Previously, we
      have designed death receptor-specific TRAIL variants that induce apoptosis
      exclusively via one of its death receptors. Here, we have studied in detail the
      interaction between recombinant human (rhTRAIL) variants and OPG. We show that a
      DR5-specific variant (rhTRAIL D269H/E195R) displays a significantly decreased
      affinity to OPG. Furthermore, this rhTRAIL variant shows a much higher activity
      when compared with rhTRAIL WT and retains its effectiveness in inducing cell
      death in multiple myeloma cell lines, in the presence of OPG secreted by stromal
      cells. We also demonstrate that stromal cells are largely insensitive to high
      concentrations of this rhTRAIL variant. In conclusion, rhTRAIL D269H/E195R is a
      potential therapy for multiple myeloma due to its high effectiveness and
      diminished binding to OPG. 

PMID- 24280213
TI  - De novo synthesis of steroids and oxysterols in adipocytes.
AB  - Local production and action of cholesterol metabolites such as steroids or
      oxysterols within endocrine tissues are currently recognized as an important
      principle in the cell type- and tissue-specific regulation of hormone effects. In
      adipocytes, one of the most abundant endocrine cells in the human body, the de
      novo production of steroids or oxysterols from cholesterol has not been examined.
      Here, we demonstrate that essential components of cholesterol transport and
      metabolism machinery in the initial steps of steroid and/or oxysterol
      biosynthesis pathways are present and active in adipocytes. The ability of
      adipocyte CYP11A1 in producing pregnenolone is demonstrated for the first time,
      rendering adipocyte a steroidogenic cell. The oxysterol 27-hydroxycholesterol
      (27HC), synthesized by the mitochondrial enzyme CYP27A1, was identified as one of
      the major de novo adipocyte products from cholesterol and its precursor
      mevalonate. Inhibition of CYP27A1 activity or knockdown and deletion of the
      Cyp27a1 gene induced adipocyte differentiation, suggesting a paracrine or
      autocrine biological significance for the adipocyte-derived 27HC. These findings
      suggest that the presence of the 27HC biosynthesis pathway in adipocytes may
      represent a defense mechanism to prevent the formation of new fat cells upon
      overfeeding with dietary cholesterol. 

PMID- 24280214
TI  - The MF6p/FhHDM-1 major antigen secreted by the trematode parasite Fasciola
      hepatica is a heme-binding protein.
AB  - Blood-feeding parasites have developed biochemical mechanisms to control heme
      intake and detoxification. Here we show that a major antigen secreted by Fasciola
      hepatica, previously reported as MF6p, of unknown function (gb|CCA61804.1), and
      as FhHDM-1, considered to be a helminth defense molecule belonging to the family
      of cathelicidin-like proteins (gb|ADZ24001.1), is in fact a heme-binding protein.
      The heme-binding nature of the MF6p/FhHDM-1 protein was revealed in two
      independent experiments: (i) immunopurification of the secreted protein.heme
      complexes with mAb MF6 and subsequent analysis by C8 reversed-phase HPLC and
      MS/MS spectrometry and (ii) analysis of the binding ability of the synthetic
      protein to hemin in vitro. By immunohistochemistry analysis, we have observed
      that MF6p/FhHDM-1 is produced by parenchymal cells and transported to other
      tissues (e.g. vitellaria and testis). Interestingly, MF6p/FhHDM-1 is absent both
      in the intestinal cells and in the lumen of cecum, but it can be released through
      the tegumental surface to the external medium, where it binds to free heme
      molecules regurgitated by the parasite after hemoglobin digestion. Proteins that
      are close analogs of the Fasciola MF6p/FhHDM-1 are present in other trematodes,
      including Clonorchis, Opistorchis, Paragonimus, Schistosoma, and Dicrocoelium.
      Using UV-visible spectroscopy and immunoprecipitation techniques, we observed
      that synthetic MF6p/FhHDM-1 binds to hemin with 1:1 stoichiometry and an apparent
      Kd of 1.14 * 10(-6) M(-1). We also demonstrated that formation of synthetic
      MF6p/FhHDM-1.hemin complexes inhibited hemin degradation by hydrogen peroxide and
      hemin peroxidase-like activity in vitro. Our results suggest that MF6p/FhHDM-1
      may be involved in heme homeostasis in trematodes.

PMID- 24280216
TI  - Paradoxical abatement of striatal dopaminergic transmission by cocaine and
      methylphenidate.
AB  - We combined in vitro amperometric, optical analysis of fluorescent false
      neurotransmitters and microdialysis techniques to unveil that cocaine and
      methylphenidate induced a marked depression of the synaptic release of dopamine
      (DA) in mouse striatum. In contrast to the classical dopamine transporter (DAT)
      dependent enhancement of the dopaminergic signal observed at concentrations of
      cocaine lower than 3 MUM, the inhibitory effect of cocaine was found at
      concentrations higher than 3 MUM. The paradoxical inhibitory effect of cocaine
      and methylphenidate was associated with a decrease in synapsin phosphorylation.
      Interestingly, a cocaine-induced depression of DA release was only present in
      cocaine-insensitive animals (DAT-CI). Similar effects of cocaine were produced by
      methylphenidate in both wild-type and DAT-CI mice. On the other hand, nomifensine
      only enhanced the dopaminergic signal either in wild-type or in DAT-CI mice.
      Overall, these results indicate that cocaine and methylphenidate can increase or
      decrease DA neurotransmission by blocking reuptake and reducing the exocytotic
      release, respectively. The biphasic reshaping of DA neurotransmission could
      contribute to different behavioral effects of psychostimulants, including the
      calming ones, in attention deficit hyperactivity disorder.

PMID- 24280215
TI  - Proteome analysis and conditional deletion of the EAAT2 glutamate transporter
      provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice.
AB  - Islet function is incompletely understood in part because key steps in glutamate
      handling remain undetermined. The glutamate (excitatory amino acid) transporter 2
      (EAAT2; Slc1a2) has been hypothesized to (a) provide islet cells with glutamate,
      (b) protect islet cells against high extracellular glutamate concentrations, (c)
      mediate glutamate release, or (d) control the pH inside insulin secretory
      granules. Here we floxed the EAAT2 gene to produce the first conditional EAAT2
      knock-out mice. Crossing with Nestin-cyclization recombinase (Cre) eliminated
      EAAT2 from the brain, resulting in epilepsy and premature death, confirming the
      importance of EAAT2 for brain function and validating the genetic construction.
      Crossing with insulin-Cre lines (RIP-Cre and IPF1-Cre) to obtain pancreas
      selective deletion did not appear to affect survival, growth, glucose tolerance,
      or beta-cell number. We found (using TaqMan RT-PCR, immunoblotting,
      immunocytochemistry, and proteome analysis) that the EAAT2 levels were too low to
      support any of the four hypothesized functions. The proteome analysis detected
      more than 7,000 islet proteins of which more than 100 were transporters. Although
      mitochondrial glutamate transporters and transporters for neutral amino acids
      were present at high levels, all other transporters with known ability to
      transport glutamate were strikingly absent. Glutamate-metabolizing enzymes were
      abundant. The level of glutamine synthetase was 2 orders of magnitude higher than
      that of glutaminase. Taken together this suggests that the uptake of glutamate by
      islets from the extracellular fluid is insignificant and that glutamate is
      intracellularly produced. Glutamine synthetase may be more important for islets
      than assumed previously. 

PMID- 24280217
TI  - Interleukin-4 induces up-regulation of endothelial cell claudin-5 through
      activation of FoxO1: role in protection from complement-mediated injury.
AB  - Injury to endothelial cells (ECs) often results in cell retraction and gap
      formation. When caused by antigen aggregation or complement, this injury can be
      prevented by pretreatment of the ECs with IL-4, suggesting that IL-4 modifies the
      intercellular junction. Therefore, we investigated the effects of IL-4 on
      expression of intercellular junction proteins and whether such effects are
      required for IL-4-induced resistance of ECs against complement-mediated injury.
      We found that IL-4 induces upregulation of the junction protein claudin-5 in
      porcine ECs through activation of Jak/STAT6 and phosphorylation and translocation
      of FoxO1 from the nucleus to the cytoplasm. Increased claudin-5 expression
      resulted in increased transmembrane electrical resistance of the endothelial
      monolayer and participated in IL-4-induced protection of the ECs from complement
      injury. Down-regulation of FoxO1 using siRNA by itself caused up-regulation of
      claudin-5 expression and partial protection from cytotoxicity. This protection
      was enhanced by stimulation with IL-4. We previously reported that increased
      phospholipid synthesis and mitochondrial protection were required for IL-4
      induced resistance of ECs against complement injury and now we demonstrate a
      contribution of claudin-5 expression in IL-4-induced protection.

PMID- 24280218
TI  - A novel mercuric reductase from the unique deep brine environment of Atlantis II
      in the Red Sea.
AB  - A unique combination of physicochemical conditions prevails in the lower
      convective layer (LCL) of the brine pool at Atlantis II (ATII) Deep in the Red
      Sea. With a maximum depth of over 2000 m, the pool is characterized by acidic pH
      (5.3), high temperature (68  degrees C), salinity (26%), low light levels,
      anoxia, and high concentrations of heavy metals. We have established a
      metagenomic dataset derived from the microbial community in the LCL, and here we
      describe a gene for a novel mercuric reductase, a key component of the bacterial
      detoxification system for mercuric and organomercurial species. The metagenome
      derived gene and an ortholog from an uncultured soil bacterium were synthesized
      and expressed in Escherichia coli. The properties of their products show that, in
      contrast to the soil enzyme, the ATII-LCL mercuric reductase is functional in
      high salt, stable at high temperatures, resistant to high concentrations of
      Hg(2+), and efficiently detoxifies Hg(2+) in vivo. Interestingly, despite the
      marked functional differences between the orthologs, their amino acid sequences
      differ by less than 10%. Site-directed mutagenesis and kinetic analysis of the
      mutant enzymes, in conjunction with three-dimensional modeling, have identified
      distinct structural features that contribute to extreme halophilicity,
      thermostability, and high detoxification capacity, suggesting that these were
      acquired independently during the evolution of this enzyme. Thus, our work
      provides fundamental structural insights into a novel protein that has undergone
      multiple biochemical and biophysical adaptations to promote the survival of
      microorganisms that reside in the extremely demanding environment of the ATII
      LCL. 

PMID- 24280219
TI  - O-linked beta-N-acetylglucosamine (O-GlcNAc) site thr-87 regulates synapsin I
      localization to synapses and size of the reserve pool of synaptic vesicles.
AB  - O-GlcNAc is a carbohydrate modification found on cytosolic and nuclear proteins.
      Our previous findings implicated O-GlcNAc in hippocampal presynaptic plasticity.
      An important mechanism in presynaptic plasticity is the establishment of the
      reserve pool of synaptic vesicles (RPSV). Dynamic association of synapsin I with
      synaptic vesicles (SVs) regulates the size and release of RPSV. Disruption of
      synapsin I function results in reduced size of the RPSV, increased synaptic
      depression, memory deficits, and epilepsy. Here, we investigate whether O-GlcNAc
      directly regulates synapsin I function in presynaptic plasticity. We found that
      synapsin I is modified by O-GlcNAc during hippocampal synaptogenesis in the rat.
      We identified three novel O-GlcNAc sites on synapsin I, two of which are known
      Ca(2+)/calmodulin-dependent protein kinase II phosphorylation sites. All O-GlcNAc
      sites mapped within the regulatory regions on synapsin I. Expression of synapsin
      I where a single O-GlcNAc site Thr-87 was mutated to alanine in primary
      hippocampal neurons dramatically increased localization of synapsin I to
      synapses, increased density of SV clusters along axons, and the size of the RPSV,
      suggesting that O-GlcNAcylation of synapsin I at Thr-87 may be a mechanism to
      modulate presynaptic plasticity. Thr-87 is located within an amphipathic lipid
      packing sensor (ALPS) motif, which participates in targeting of synapsin I to
      synapses by contributing to the binding of synapsin I to SVs. We discuss the
      possibility that O-GlcNAcylation of Thr-87 interferes with folding of the ALPS
      motif, providing a means for regulating the association of synapsin I with SVs as
      a mechanism contributing to synapsin I localization and RPSV generation. 

PMID- 24280220
TI  - Phosphoregulation of the titin-cap protein telethonin in cardiac myocytes.
AB  - Telethonin (also known as titin-cap or t-cap) is a muscle-specific protein whose
      mutation is associated with cardiac and skeletal myopathies through unknown
      mechanisms. Our previous work identified cardiac telethonin as an interaction
      partner for the protein kinase D catalytic domain. In this study, kinase assays
      used in conjunction with MS and site-directed mutagenesis confirmed telethonin as
      a substrate for protein kinase D and Ca(2+)/calmodulin-dependent kinase II in
      vitro and identified Ser-157 and Ser-161 as the phosphorylation sites. Phosphate
      affinity electrophoresis and MS revealed endogenous telethonin to exist in a
      constitutively bis-phosphorylated form in isolated adult rat ventricular myocytes
      and in mouse and rat ventricular myocardium. Following heterologous expression in
      myocytes by adenoviral gene transfer, wild-type telethonin became bis
      phosphorylated, whereas S157A/S161A telethonin remained non-phosphorylated.
      Nevertheless, both proteins localized predominantly to the sarcomeric Z-disc,
      where they partially replaced endogenous telethonin. Such partial replacement
      with S157A/S161A telethonin disrupted transverse tubule organization and
      prolonged the time to peak of the intracellular Ca(2+) transient and increased
      its variance. These data reveal, for the first time, that cardiac telethonin is
      constitutively bis-phosphorylated and suggest that such phosphorylation is
      critical for normal telethonin function, which may include maintenance of
      transverse tubule organization and intracellular Ca(2+) transients. 

PMID- 24280221
TI  - Neuroprotective role of the basic leucine zipper transcription factor NFIL3 in
      models of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by the loss of motor neurons. Here we show that the basic leucine zipper
      transcription factor NFIL3 (also called E4BP4) confers neuroprotection in models
      of ALS. NFIL3 is up-regulated in primary neurons challenged with neurotoxic
      insults and in a mouse model of ALS. Overexpression of NFIL3 attenuates
      excitotoxic neuronal damage and protects neurons against neurodegeneration in a
      cell-based ALS model. Conversely, reduction of NFIL3 exacerbates neuronal demise
      in adverse conditions. Transgenic neuronal expression of NFIL3 in ALS mice delays
      disease onset and attenuates motor axon and neuron degeneration. These results
      suggest that NFIL3 plays a neuroprotective role in neurons and constitutes a
      potential therapeutic target for neurodegeneration. 

PMID- 24280222
TI  - Multimeric growth hormone receptor complexes serve as signaling platforms.
AB  - Growth hormone (GH) signaling is required for promoting longitudinal body growth,
      stem cell activation, differentiation, and survival and for regulation of
      metabolism. Failure to adequately regulate GH signaling leads to disease:
      excessive GH signaling has been connected to cancer, and GH insensitivity has
      been reported in cachexia patients. Since its discovery in 1989, the receptor has
      served a pivotal role as the prototype cytokine receptor both structurally and
      functionally. Phosphorylation and ubiquitylation regulate the GH receptor (GHR)
      at the cell surface: two ubiquitin ligases (SCF(betaTrCP2) and CHIP) determine
      the GH responsiveness of cells by controlling its endocytosis, whereas JAK2
      initiates the JAK/STAT pathway. We used blue native electrophoresis to identify
      phosphorylated and ubiquitylated receptor intermediates. We show that GHRs occur
      as ~500-kDa complexes that dimerize into active ~900-kDa complexes upon GH
      binding. The dimerized complexes act as platforms for transient interaction with
      JAK2 and ubiquitin ligases. If GH and receptors are made in the same cell
      (autocrine mode), only limited numbers of ~900-kDa complexes are formed. The
      experiments reveal the dynamic changes in post-translational modifications during
      GH-induced signaling events and show that relatively simple cytokine receptors
      like GHRs are able to form higher order protein complexes. Insight in the complex
      formation of cytokine receptors is crucially important for engineering cytokines
      that control ligand-induced cell responses and for generating a new class of
      therapeutic agents for a wide range of diseases. 

PMID- 24280223
TI  - Extracellular calcium modulates actions of orthosteric and allosteric ligands on
      metabotropic glutamate receptor 1alpha.
AB  - Metabotropic glutamate receptor 1alpha (mGluR1alpha), a member of the family C G
      protein-coupled receptors, is emerging as a potential drug target for various
      disorders, including chronic neuronal degenerative diseases. In addition to being
      activated by glutamate, mGluR1alpha is also modulated by extracellular Ca(2+).
      However, the underlying mechanism is unknown. Moreover, it has long been
      challenging to develop receptor-specific agonists due to homologies within the
      mGluR family, and the Ca(2+)-binding site(s) on mGluR1alpha may provide an
      opportunity for receptor-selective targeting by therapeutics. In the present
      study, we show that our previously predicted Ca(2+)-binding site in the hinge
      region of mGluR1alpha is adjacent to the site where orthosteric agonists and
      antagonists bind on the extracellular domain of the receptor. Moreover, we found
      that extracellular Ca(2+) enhanced mGluR1alpha-mediated intracellular Ca(2+)
      responses evoked by the orthosteric agonist l-quisqualate. Conversely,
      extracellular Ca(2+) diminished the inhibitory effect of the mGluR1alpha
      orthosteric antagonist (S)-alpha-methyl-4-carboxyphenylglycine. In addition,
      selective positive (Ro 67-4853) and negative (7
      (hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester) allosteric
      modulators of mGluR1alpha potentiated and inhibited responses to extracellular
      Ca(2+), respectively, in a manner similar to their effects on the response of
      mGluR1alpha to glutamate. Mutations at residues predicted to be involved in
      Ca(2+) binding, including E325I, had significant effects on the modulation of
      responses to the orthosteric agonist l-quisqualate and the allosteric modulator
      Ro 67-4853 by extracellular Ca(2+). These studies reveal that binding of
      extracellular Ca(2+) to the predicted Ca(2+)-binding site in the extracellular
      domain of mGluR1alpha modulates not only glutamate-evoked signaling but also the
      actions of both orthosteric ligands and allosteric modulators on mGluR1alpha. 

PMID- 24280224
TI  - Intranuclear aggregation of mutant FUS/TLS as a molecular pathomechanism of
      amyotrophic lateral sclerosis.
AB  - Dominant mutations in FUS/TLS cause a familial form of amyotrophic lateral
      sclerosis (fALS), where abnormal accumulation of mutant FUS proteins in cytoplasm
      has been observed as a major pathological change. Many of pathogenic mutations
      have been shown to deteriorate the nuclear localization signal in FUS and thereby
      facilitate cytoplasmic mislocalization of mutant proteins. Several other
      mutations, however, exhibit no effects on the nuclear localization of FUS in
      cultured cells, and their roles in the pathomechanism of fALS remain obscure.
      Here, we show that a pathogenic mutation, G156E, significantly increases the
      propensities for aggregation of FUS in vitro and in vivo. Spontaneous in vitro
      formation of amyloid-like fibrillar aggregates was observed in mutant but not
      wild-type FUS, and notably, those fibrils functioned as efficient seeds to
      trigger the aggregation of wild-type protein. In addition, the G156E mutation did
      not disturb the nuclear localization of FUS but facilitated the formation of
      intranuclear inclusions in rat hippocampal neurons with significant cytotoxicity.
      We thus propose that intranuclear aggregation of FUS triggered by a subset of
      pathogenic mutations is an alternative pathomechanism of FUS-related fALS
      diseases. 

PMID- 24280227
TI  - Flow-induced wall mechanics of patient-specific aneurysmal cerebral arteries:
      Nonlinear isotropic versus anisotropic wall stress.
AB  - Fluid-structure interaction simulations of three patient-specific models of
      cerebral aneurysms were carried out with the objective of quantifying the effects
      of non-Newtonian blood flow and the vessel mechanical behavior on the time
      dependent fluid shear and normal stresses, and structural stress and stretch. The
      average wall shear stress at peak systole was found to be approximately one order
      of magnitude smaller than the shear stresses in the proximal communicating
      arteries, regardless of the shape or size of the aneurysms. Spatial distributions
      of oscillatory shear index were consistent with the reciprocal of wall shear
      stress distributions at peak systole for all aneurysm geometries, demonstrating
      that oscillatory shear index correlates inversely with wall shear at this time
      point in the cardiac cycle. An aneurysm wall modeled with an isotropic material
      resulted in an underestimation of both the maximum principal stress and stretch,
      compared to the anisotropic material model. For the three aneurysm geometries,
      anisotropic peak wall stresses were approximately 50% higher than for an
      isotropic material. Regardless of the constitutive material, the maximum stresses
      were consistently located at the aneurysm neck; stresses in the dome were 30% of
      those in the neck. 

PMID- 24280228
TI  - Mechanical behaviour of the in vivo paediatric and adult trunk during respiratory
      physiotherapy.
AB  - The load-deflection response of the human trunk has been studied using various
      methods. The different shapes observed may be due to the methodology and the
      population. The purpose of this study is to quantify and explain the in vivo
      mechanical response of paediatric and adult trunks during respiratory
      physiotherapy. Eight children aged 5-15 months and eight healthy adult volunteers
      aged 30-87 years participated in this study. The force applied by the
      physiotherapist and the displacement of the targets on his hands were recorded.
      Parameters were also measured and calculated to compare against other studies.
      Time lags between force time histories and displacement time histories were
      observed on both children and adults. Different time lags resulted in different
      shapes of the force-displacement curves. Factors including respiration, muscle
      contraction and loading pattern are part of the assumptions used to explain this
      phenomenon. The maximum displacements of the paediatric and adult trunks were 18
      and 44 mm, respectively, with a maximum load of 208 and 250 N, respectively. This
      study provides a better explanation of the peculiar force-displacement
      characteristics of both living and active children and adults under a non
      injurious, low-rate compression condition. Complementary data (e.g. muscle
      activity and breathing) should be collected in the future to go towards in vivo
      human trunk modelling. 

PMID- 24280225
TI  - Conserved distal loop residues in the Hsp104 and ClpB middle domain contact
      nucleotide-binding domain 2 and enable Hsp70-dependent protein disaggregation.
AB  - The homologous hexameric AAA(+) proteins, Hsp104 from yeast and ClpB from
      bacteria, collaborate with Hsp70 to dissolve disordered protein aggregates but
      employ distinct mechanisms of intersubunit collaboration. How Hsp104 and ClpB
      coordinate polypeptide handover with Hsp70 is not understood. Here, we define
      conserved distal loop residues between middle domain (MD) helix 1 and 2 that are
      unexpectedly critical for Hsp104 and ClpB collaboration with Hsp70. Surprisingly,
      the Hsp104 and ClpB MD distal loop does not contact Hsp70 but makes intrasubunit
      contacts with nucleotide-binding domain 2 (NBD2). Thus, the MD does not
      invariably project out into solution as in one structural model of Hsp104 and
      ClpB hexamers. These intrasubunit contacts as well as those between MD helix 2
      and NBD1 are different in Hsp104 and ClpB. NBD2-MD contacts dampen disaggregase
      activity and must separate for protein disaggregation. We demonstrate that ClpB
      requires DnaK more stringently than Hsp104 requires Hsp70 for protein
      disaggregation. Thus, we reveal key differences in how Hsp104 and ClpB coordinate
      polypeptide handover with Hsp70, which likely reflects differential tuning for
      yeast and bacterial proteostasis. 

PMID- 24280226
TI  - Prion infection impairs cholesterol metabolism in neuronal cells.
AB  - Conversion of prion protein (PrP(C)) into a pathological isoform (PrP(Sc)) during
      prion infection occurs in lipid rafts and is dependent on cholesterol. Here, we
      show that prion infection increases the abundance of cholesterol transporter, ATP
      binding cassette transporter type A1 (ATP-binding cassette transporter type A1),
      but reduces cholesterol efflux from neuronal cells leading to the accumulation of
      cellular cholesterol. Increased abundance of ABCA1 in prion disease was confirmed
      in prion-infected mice. Mechanistically, conversion of PrP(C) to the pathological
      isoform led to PrP(Sc) accumulation in rafts, displacement of ABCA1 from rafts
      and the cell surface, and enhanced internalization of ABCA1. These effects were
      abolished with reversal of prion infection or by loading cells with cholesterol.
      Stimulation of ABCA1 expression with liver X receptor agonist or overexpression
      of heterologous ABCA1 reduced the conversion of prion protein into the
      pathological form upon infection. These findings demonstrate a reciprocal
      connection between prion infection and cellular cholesterol metabolism, which
      plays an important role in the pathogenesis of prion infection in neuronal cells.

PMID- 24280229
TI  - [The Bulletin du cancer: the years before the First World War].
AB  - Three years after its founding in 1909, the Association francaise pour l'etude du
      cancer is a major scientific society developing transdisciplinary debates
      particularly on innovative therapeutics in cancer, such as the developing use of
      radium. The Association at that time assembles together all the French medical
      elite. Reading the Bulletin offers a clear view of the brilliant monthly debates.
      First World War stopped the life of the Association for four years. After this
      break, the set up of dedicated centers for cancer treatment was responsible for a
      major turn in the Association's life. 

PMID- 24280230
TI  - Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer
      cells.
AB  - BACKGROUND: Loss of function of fumarate hydratase (FH), the mitochondrial tumor
      suppressor and tricarboxylic acid (TCA) cycle enzyme, is associated with a highly
      malignant form of papillary and collecting duct renal cell cancer. The
      accumulation of fumarate in these cells has been linked to the tumorigenic
      process. However, little is known about the overall effects of the loss of FH on
      cellular metabolism. METHODS: We performed comprehensive metabolomic analyses of
      urine from Fh1-deficient mice and stable isotopologue tracing from human and
      mouse FH-deficient cell lines to investigate the biochemical signature of the
      loss of FH. RESULTS: The metabolomics analysis revealed that the urea cycle
      metabolite argininosuccinate is a common metabolic biomarker of FH deficiency.
      Argininosuccinate was found to be produced from arginine and fumarate by the
      reverse activity of the urea cycle enzyme argininosuccinate lyase (ASL), making
      these cells auxotrophic for arginine. Depleting arginine from the growth media by
      the addition of pegylated arginine deiminase (ADI-PEG 20) decreased the
      production of argininosuccinate in FH-deficient cells and reduced cell survival
      and proliferation. CONCLUSIONS: These results unravel a previously unidentified
      correlation between fumarate accumulation and the urea cycle enzyme ASL in FH
      deficient cells. The finding that FH-deficient cells become auxotrophic for
      arginine opens a new therapeutic perspective for the cure of hereditary
      leiomyomatosis and renal cell cancer (HLRCC).

PMID- 24280231
TI  - Clinical effectiveness and cost-effectiveness of second- and third-generation
      left ventricular assist devices as either bridge to transplant or alternative to
      transplant for adults eligible for heart transplantation: systematic review and
      cost-effectiveness model.
AB  - BACKGROUND: Advanced heart failure (HF) is a debilitating condition for which
      heart transplant (HT) offers the best treatment option. However, the supply of
      donor hearts is diminishing and demand greatly exceeds supply. Ventricular assist
      devices (VADs) are surgically implanted pumps used as an alternative to
      transplant (ATT) or as a bridge to transplant (BTT) while a patient awaits a
      donor heart. Surgery and VADs are costly. For the NHS to allocate and deliver
      such services in a cost-effective way the relative costs and benefits of these
      alternative treatments need to be estimated. OBJECTIVES: To investigate for
      patients aged >= 16 years with advanced HF eligible for HT: (1) the clinical
      effectiveness and cost-effectiveness of second- and third-generation VADs used as
      BTT compared with medical management (MM); and (2) the clinical effectiveness and
      cost-effectiveness of second- and third-generation VADs used as an ATT in
      comparison with their use as BTT therapy. DATA SOURCES: Searches for clinical
      effectiveness studies covered years from 2003 to March 2012 and included the
      following data bases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations,
      EMBASE, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of
      Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA
      databases [NHS Centre for Reviews and Dissemination (CRD)], Science Citation
      Index and Conference Proceedings (Web of Science), UK Clinical Research Network
      (UKCRN) Portfolio Database, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), PsycINFO and National Library of Medicine (NLM) Gateway,
      Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled
      Trials and ClinicalTrials.gov. Reference lists of relevant articles were checked,
      and VAD manufacturers' websites interrogated. For economic analyses we made use
      of individual patient data (IPD) held in the UK Blood and Transplant Database
      (BTDB). REVIEW METHODS: Systematic reviews of evidence on clinical effectiveness
      and cost-effectiveness of second- and third-generation US Food and Drug
      Administration (FDA) and/or Conformite Europeenne (CE) approved VADs.
      Publications from the last 5 years with control groups, or case series with 50 or
      more patients were included. Outcomes included survival, functional capacity
      (e.g. change in New York Heart Association functional classification), quality of
      life (QoL) and adverse events. Data from the BTDB were obtained. A discrete-time,
      semi-Markov, multistate model was built. Deterministic and probabilistic methods
      with multiple sensitivity analyses varying survival, utilities and cost inputs to
      the model were used. Model outputs were incremental cost-effectiveness ratios
      (ICERs), cost/quality-adjusted life-years (QALYs) gained and cost/life-year
      gained (LYG). The discount rate was 3.5% and the time horizon varied over 3
      years, 10 years and lifetime. RESULTS: Forty publications reported clinical
      effectiveness of VADs and one study reported cost-effectiveness. We found no high
      quality comparative empirical studies of VADs as BTT compared with MM or as ATT
      compared with BTT. Approximately 15-25% of the patients receiving a device had
      died by 12 months. Studies reported the following wide ranges for adverse events:
      4-27% bleeding requiring transfusion; 1.5-40% stroke; 3.3-48% infection; 1-14%
      device failure; 3-30% HF; 11-32% reoperation; and 3-53% renal failure. QoL and
      functional status were reported as improved in studies of two devices [HeartMate
      II (HMII; Thoratec Inc., Pleasanton, CA, USA) and HeartWare (HW; HeartWare Inc.,
      Framingham, MA, USA)]. At 3 years, 10 years and lifetime, the ICERs for VADs as
      BTT compared with MM were L122,730, L68,088 and L55,173 respectively. These
      values were stable to changes in survival of the MM group. Both QoL and costs
      were reduced by VADs as ATT compared with VADs as BTT giving ICERs in south-west
      quadrant of the cost effectiveness plain (cost saving/QALY sacrificed) of
      L353,467, L31,685 and L20,637 over the 3 years, 10 years and lifetime horizons
      respectively. Probabilistic analyses yielded similar results for both research
      questions. LIMITATIONS: Conclusions about the clinical effectiveness were limited
      by the lack of randomised controlled trials (RCTs) comparing the effectiveness of
      different VADs for BTT or comparing BTT with any alternative treatment and by the
      overlapping populations in published studies. Although IPD from the BTDB was used
      to estimate the cost-effectiveness of VADs compared with MM for BTT, the lack of
      randomisation of populations limited the interpretation of this analysis.
      CONCLUSIONS: At 3 years, 10 years and lifetime the ICERs for VADs as BTT compared
      with MM are higher than generally applied willingness-to-pay thresholds in the
      UK, but at a lifetime time horizon they approximate threshold values used in end
      of life assessments. VADs as ATT have a reduced cost but cause reduced QALYs
      relative to BTT. Future research should direct attention towards two areas.
      First, how any future evaluations of second- or third-generation VADs might be
      conducted. For ethical reasons a RCT offering equal probability of HT for each
      group would not be feasible; future studies should fully assess costs, long-term
      patient survival, QoL, functional ability and adverse events, so that these may
      be incorporated into economic evaluation agreement on outcomes measures across
      future studies. Second, continuation of accurate data collection in the UK
      database to encompass QoL data and comparative assessment of performance with
      other international centres. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 24280232
TI  - Clinical variability of respiratory pulmonary hypertension: implications for
      diagnosis and management.
AB  - Pulmonary Hypertension (PH) associated to chronic respiratory diseases is
      currently classified in the 3rd group, as a mild to moderate form of pre
      capillary PH that progressively complicates the prognosis of associated pulmonary
      disease. In clinical practice, however, some unresolved issues in the respiratory
      PH should be considered: 1) the PH heterogeneity in some respiratory diseases,
      such as Chronic Obstructive Pulmonary Disease (COPD), where the prevalence of
      unrecognized left heart disease, or chronic pulmonary thromboembolism may change
      the clinical classification; 2) the combining form of severe PH which often is
      not correlated to chronic ventilator impairment, while outcome is strictly
      related to pulmonary haemodynamics. The recognition of out of proportion
      respiratory PH in several chronic respiratory diseases which include COPD,
      Idiopathic Pulmonary Fibrosis (IPF), Combined Pulmonary Fibrosis and Emphysema,
      Obstructive Sleep Apnea (OSA), Obesity Hypoventilation Syndrome (OHS) may be
      important for a comprehensive clinical classification of severe respiratory PH,
      as well as, for the inclusion of these patients in randomized clinical trials on
      PH targeted therapy. 

PMID- 24280233
TI  - Review: placenta-specific microRNAs in exosomes - good things come in nano
      packages.
AB  - MicroRNAs (miRNAs) are small noncoding RNA gene products that commonly regulate
      mRNA expression by repression of translation and/or transcript decay. Whereas
      common and unique types of miRNAs are expressed by the placenta during pregnancy,
      the functions of most placental miRNA species are unknown. In addition to their
      intracellular silencing function, miRNAs are also released to the extracellular
      space and systemic circulation, where they can potentially target cells to
      regulate mRNA and protein expression, providing a non-hormonal means of
      intercellular communication that contributes to tissue homeostasis and disease
      pathophysiology. This review centers on extracellular miRNAs that originate in
      trophoblasts and that could mediate crosstalk between the feto-placental unit and
      the mother during pregnancy. We specifically detail the function of miRNAs from
      the primate-specific chromosome 19 miRNA cluster. These miRNAs are highly
      expressed in human placentas and in the serum of pregnant women. They are also
      packaged into extracellular vesicles of diverse sizes, including exosomes, and
      endow non-trophoblastic cells with resistance to a variety of viruses. 

PMID- 24280234
TI  - The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to
      potential new hypotheses of IUGR origin/development.
AB  - INTRODUCTION: Intrauterine Growth Restriction (IUGR) is a multifactorial disease
      defined by an inability of the fetus to reach its growth potential. IUGR not only
      increases the risk of neonatal mortality/morbidity, but also the risk of
      metabolic syndrome during adulthood. Certain placental proteins have been shown
      to be implicated in IUGR development, such as proteins from the GH/IGF axis and
      angiogenesis/apoptosis processes. METHODS: Twelve patients with term IUGR
      pregnancy (birth weight < 10th percentile) and 12 CTRLs were included. mRNA was
      extracted from the fetal part of the placenta and submitted to a subtraction
      method (Clontech PCR-Select cDNA Subtraction). RESULTS: One candidate gene
      identified was the long non-coding RNA NEAT1 (nuclear paraspeckle assembly
      transcript 1). NEAT1 is the core component of a subnuclear structure called
      paraspeckle. This structure is responsible for the retention of hyperedited mRNAs
      in the nucleus. Overall, NEAT1 mRNA expression was 4.14 (+/-1.16)-fold increased
      in IUGR vs. CTRL placentas (P = 0.009). NEAT1 was exclusively localized in the
      nuclei of the villous trophoblasts and was expressed in more nuclei and with
      greater intensity in IUGR placentas than in CTRLs. PSPC1, one of the three main
      proteins of the paraspeckle, co-localized with NEAT1 in the villous trophoblasts.
      The expression of NEAT1_2 mRNA, the long isoform of NEAT1, was only modestly
      increased in IUGR vs. CTRL placentas. DISCUSSION/CONCLUSION: The increase in
      NEAT1 and its co-localization with PSPC1 suggests an increase in paraspeckles in
      IUGR villous trophoblasts. This could lead to an increased retention of important
      mRNAs in villous trophoblasts nuclei. Given that the villous trophoblasts are
      crucial for the barrier function of the placenta, this could in part explain
      placental dysfunction in idiopathic IUGR fetuses.

PMID- 24280235
TI  - Genetic diversity of arsenic accumulation in rice and QTL analysis of methylated
      arsenic in rice grains.
AB  - BACKGROUND: Rice is a major source of dietary intake of arsenic (As) for the
      populations that consume rice as a staple food. Therefore, it is necessary to
      reduce the As concentration in rice to avoid the potential risk to human health.
      In this study, the genetic diversity in As accumulation and As speciation in rice
      grains was investigated using a world rice core collection (WRC) comprising 69
      accessions grown over a 3-year period. Moreover, quantitative trait locus (QTL)
      analysis was conducted to identify QTLs controlling the dimethylarsinic acid
      (DMA) content of rice grains. RESULTS: There was a 3-fold difference in the grain
      As concentration of WRC. Concentrations of total-As, inorganic As, and DMA were
      significantly affected by genotype, year, and genotype-year interaction effects.
      Among the WRC accessions, Local Basmati and Tima (indica type) were identified as
      cultivars with the lowest stable total-As and inorganic As concentrations. Using
      an F2 population derived from Padi Perak (a high-DMA accession) and Koshihikari
      (a low-DMA cultivar), we identified two QTLs on chromosome 6 (qDMAs6.1 and
      qDMAs6.2) and one QTL on chromosome 8 (qDMAs8) that were responsible for
      variations in the grain DMA concentration. Approximately 73% of total phenotypic
      variance in DMA was explained by the three QTLs. CONCLUSIONS: Based on the
      results provided, one strategy for developing rice cultivars with a low level of
      toxic As would be to change the proportion of organic As on the basis of a low
      level of total As content.

PMID- 24280236
TI  - Insights on activity and stability of subtilisin E towards guanidinium chloride
      and sodium dodecylsulfate.
AB  - A subtilisin E variant (M4) showing high activity and resistance towards
      guanidinium chloride (GdmCl) and sodium dodecylsulfate (SDS) was previously
      identified after three rounds of directed evolution [Li et al., ChemBioChem 2012,
      13(5), 691-699.]. In this report, 10 additional positions, identified during
      directed subtilisin E evolution, were saturated on the previously reported SeSaM1
      5 variant (S62/A153/G166/I205). Screening confirmed that chaotolerant variants
      included amino acid substitutions either in the active site, or the substrate
      binding pocket. Two variants, M5 (S62I/A153V/G166S/T224A/T240S) and M6
      (S62I/A153V/G166S/I205V/N218S/T224A) were finally generated to maximize activity
      and stability in the presence of GdmCl or SDS. The inactivation concentration
      (IC50) of M6 using Suc-AAPF-pNA as substrate was significantly increased compared
      to M4 in the presence of GdmCl (IC50 (M4): 2.7M; IC50 (M6): 4.6M) and SDS (IC50
      (M4): 1.5%; IC50 (M6): 4.0%). The half-life in 5M GdmCl was also significantly
      improved for M6 compared to M4 (t 1/2 (M4): 2min; t 1/2 (M6): 15min). M5 retained
      resistance towards GdmCl or SDS as in M4. The activity of M5 towards a complex
      protein substrate (Azocasein) was increased by ~1.5 fold compared to M4 and M6.
      Circular dichroism (CD) analysis for subtilisin E wild type (WT) and three
      variants (M4, M5 and M6) indicated that secondary structures of all variants
      including wild type at 1-2M GdmCl (except M4) were not significantly perturbed,
      with unfolding occurring for WT and all three variants above 3M GdmCl. In SDS,
      the secondary structures of WT and all three variants remained intact at
      concentrations of 0.5 to 2.0% (w/v) SDS. Results suggest that subtilisin E
      inactivation occurred most likely due to inhibitory effect, since a general
      unfolding of the enzyme was not observed through circular dichroism. Such
      inhibition could be avoided by limiting the access of GdmCl and SDS to the active
      site and/or to residues involved in substrate binding. 

PMID- 24280237
TI  - Editorial: The evolving Practice of Epidemiology.

PMID- 24280238
TI  - Immune adjuvants as critical guides directing immunity triggered by therapeutic
      cancer vaccines.
AB  - Tumor growth is controlled by natural antitumor immune responses alone or by
      augmented immune reactivity resulting from different forms of immunotherapy,
      which has demonstrated clinical benefit in numerous studies, although the overall
      percentage of patients with durable clinical responses remains limited. This is
      attributed to the heterogeneity of the disease, the inclusion of late-stage
      patients with no other treatment options and advanced tumor-associated
      immunosuppression, which may be consolidated by certain types of chemotherapy.
      Despite variable responsiveness to distinct types of immunotherapy, therapeutic
      cancer vaccination has shown meaningful efficacy for a variety of cancers. A key
      step during cancer vaccination involves the appropriate modeling of the
      functional state of dendritic cells (DCs) capable of co-delivering four critical
      signals for proper instruction of tumor antigen-specific T cells. However, the
      education of DCs, either directly in situ, or ex vivo by various complex
      procedures, lacks standardization. Also, it is questioned whether ex vivo
      prepared DC vaccines are superior to in situ-administered adjuvant-guided
      vaccines, although both approaches have shown success. Evaluation of these
      variables is further complicated by a lack of consensus in evaluating vaccination
      clinical study end points. We discuss the role of signals needed for the
      preparation of classic in situ and modern ex vivo DC vaccines capable of proper
      reprogramming of antitumor immune responses in patients with cancer. 

PMID- 24280239
TI  - Forearm ischemia decreases endothelial colony-forming cell angiogenic potential.
AB  - BACKGROUND AIMS: Circulating endothelial progenitor cells and especially
      endothelial colony-forming cells (ECFCs) are promising candidate cells for
      endothelial regenerative medicine of ischemic diseases, but the conditions for an
      optimal collection from adult blood must be improved. METHODS: On the basis of a
      recently reported vascular niche of ECFCs, we hypothesized that a local ischemia
      could trigger ECFC mobilization from the vascular wall into peripheral blood to
      optimize their collection for autologous implantation in critical leg ischemia.
      Because the target population with critical leg ischemia is composed of elderly
      patients in whom a vascular impairment has been documented, we also analyzed the
      impact of aging on ECFC mobilization and vascular integrity. RESULTS: After
      having defined optimized ECFC culture conditions, we studied the effect of
      forearm ischemia on ECFC numbers and functions in 26 healthy volunteers (13
      volunteers ages 20-30-years old versus 13 volunteers ages 60-70 years old). The
      results show that forearm ischemia induced an efficient local ischemia and a
      normal endothelial response but did not mobilize ECFCs regardless of the age
      group. Moreover, we report an alteration of angiogenic properties of ECFCs
      obtained after forearm ischemia, in vitro as well as in vivo in a hindlimb
      ischemia murine model. This impaired ECFC angiogenic potential was not associated
      with a quantitative modification of the circulating endothelial compartment.
      CONCLUSIONS: The procedure of local ischemia, although reulting in a preserved
      endothelial reactivity, did not mobilize ECFCs but altered their angiogenic
      potential.

PMID- 24280240
TI  - RNAi mediated down regulation of myo-inositol-3-phosphate synthase to generate
      low phytate rice.
AB  - BACKGROUND: Phytic acid (InsP6) is considered as the major source of phosphorus
      and inositol phosphates in cereal grains. Reduction of phytic acid level in
      cereal grains is desirable in view of its antinutrient properties to maximize
      mineral bioavailability and minimize the load of phosphorus waste management. We
      report here RNAi mediated seed-specific silencing of myo-inositol-3-phosphate
      synthase (MIPS) gene catalyzing the first step of phytic acid biosynthesis in
      rice. Moreover, we also studied the possible implications of MIPS silencing on
      myo-inositol and related metabolism, since, first step of phytic acid
      biosynthesis is also the rate limiting step of myo-inositol synthesis, catalyzed
      by MIPS. RESULTS: The resulting transgenic rice plants (T3) showed a 4.59 fold
      down regulation in MIPS gene expression, which corresponds to a significant
      decrease in phytate levels and a simultaneous increment in the amount of
      inorganic phosphate in the seeds. A diminution in the myo-inositol content of
      transgenic plants was also observed due to disruption of the first step of phytic
      acid biosynthetic pathway, which further reduced the level of ascorbate and
      altered abscisic acid (ABA) sensitivity of the transgenic plants. In addition,
      our results shows that in the transgenic plants, the lower phytate levels has led
      to an increment of divalent cations, of which a 1.6 fold increase in the iron
      concentration in milled rice seeds was noteworthy. This increase could be
      attributed to reduced chelation of divalent metal (iron) cations, which may
      correlate to higher iron bioavailability in the endosperm of rice grains.
      CONCLUSION: The present study evidently suggests that seed-specific silencing of
      MIPS in transgenic rice plants can yield substantial reduction in levels of
      phytic acid along with an increase in inorganic phosphate content. However, it
      was also demonstrated that the low phytate seeds had an undesirable diminution in
      levels of myo-inositol and ascorbate, which probably led to sensitiveness of
      seeds to abscisic acid during germination. Therefore, it is suggested that though
      MIPS is the prime target for generation of low phytate transgenic plants, down
      regulation of MIPS can have detrimental effect on myo-inositol synthesis and
      related pathways which are involved in key plant metabolism.

PMID- 24280241
TI  - Snow storm in the bronchoalveolar lavage.

PMID- 24280242
TI  - Clinical characteristics and survival in never smokers with lung cancer.
AB  - INTRODUCTION AND OBJECTIVE: To analyze the frequency, clinical characteristics
      and survival of patients with lung cancer (LC) who have never smoked in
      comparison to patients who smoke. PATIENTS AND METHODS: A retrospective study in
      patients diagnosed with LC by cytohistology between 1999 and 2011. Survival was
      estimated by the Kaplan-Meier method. The chi(2) test was used to estimate the
      relationship between the variables. RESULTS: A total of 2161 patients were
      diagnosed with LC, 396 (18.3%) of whom had never smoked. The mean age (+/
      standard deviation) in this group was 72.85+/-10.52; 64.6% were women and 35.4%
      men. According to the cytohistology, 55.6% were adenocarcinoma, 20.5% squamous
      cell, 15% small cell, 2.7% large cell and 6.2% other subtypes. The diagnosis was
      made in advanced stage (iv) in 61.4%, and 14.4% of the patients received surgical
      treatment. Survival was 12.4%, with no differences between the two groups. In the
      group of never smokers, women had better survival than men. CONCLUSIONS: Of the
      patients diagnosed with LC, 18.3% had never smoked. It was diagnosed mainly in
      women, at advanced stages and the most common histological type was
      adenocarcinoma. There were no survival differences compared to the group of
      smokers.

PMID- 24280243
TI  - Principal component modeling of isokinetic moment curves for discriminating
      between the injured and healthy knees of unilateral ACL deficient patients.
AB  - Bilateral knee strength evaluations of unilateral anterior cruciate ligament
      (ACL) deficient patients using isokinetic dynamometry are commonly performed in
      rehabilitation settings. The most frequently-used outcome measure is the peak
      moment value attained by the knee extensor and flexor muscle groups. However,
      other strength curve features may also be of clinical interest and utility. The
      purpose of this investigation was to identify, using Principal Component Analysis
      (PCA), strength curve features that explain the majority of variation between the
      injured and uninjured knee, and to assess the capabilities of these features to
      detect the presence of injury. A mixed gender cohort of 43 unilateral ACL
      deficient patients performed 6 continuous concentric knee extension and flexion
      repetitions bilaterally at 60 degrees s(-1) and 180 degrees s(-1) within a 90
      degrees  range of motion. Moment waveforms were analyzed using PCA, and binary
      logistic regression was used to develop a discriminatory decision rule. For all
      directions and speeds, a statistically significant overall reduction in strength
      was noted for the involved knee in comparison to the uninvolved knee. The
      discriminatory decision rule yielded a specificity and sensitivity of 60.5% and
      60.5%, respectively, corresponding to an accuracy of ~62%. As such, the curve
      features extracted using PCA enabled only limited clinical usefulness in
      discerning between the ACL deficient and contra lateral, healthy knee.
      Improvement in discrimination capabilities may perhaps be achieved by
      consideration of different testing speeds and contraction modes, as well as
      utilization of other data analysis techniques. 

PMID- 24280244
TI  - Innervation zones location and optimal electrodes position of obliquus internus
      and obliquus externus abdominis muscles.
AB  - The assessment of abdominal muscles has became popular in recent years because
      the study of "core muscles" is now considered a pivotal approach for a number of
      fields. The purpose of this study was to describe the innervation zone (IZ)
      locations and optimal electrode sites in two core muscles: the obliquus externus
      (OE) and the obliquus internus (OI) abdominis muscles. Twenty healthy male
      subjects were recruited and the IZ location was studied during a submaximal
      isometric contraction using multichannel surface EMG. The optimal electrode
      position for OI was found to be 2cm lower the most prominent point of the
      anterior superior iliac spine, just medial and superior to the inguinal ligament.
      The optimal electrode position for OE was found to be 14cm from the median line,
      lower the level of 1cm above umbilicus, parallel to the line extending from the
      most inferior point of the costal margin to the opposite pubic tubercle (almost
      45 degrees  with respect to the median line). Findings showed that for OI and OE
      muscles it is possible to provide indications for a muscle belly area suited for
      proper positioning of at least an electrode pair. 

PMID- 24280245
TI  - BMP activation and Wnt-signalling affect biochemistry and functional
      biomechanical properties of cartilage tissue engineering constructs.
AB  - OBJECTIVES: Bone morphogenetic protein (BMP-) and Wnt-signalling play crucial
      roles in cartilage homeostasis. Our objective was to investigate whether
      activation of the BMP-pathway or stimulation of Wnt-signalling cascades
      effectively enhances cartilage-specific extracellular matrix (ECM) accumulation
      and functional biomechanical parameters of chondrocyte-seeded tissue engineering
      (TE)-constructs. DESIGN: Articular chondrocytes were cultured in collagen-type
      I/III-matrices over 6 weeks to create a biomechanical standard curve. Effects of
      stimulation with 100 ng/mL BMP-4/-7 heterodimer or 10 mM lithium chloride (LiCl)
      on ECM-deposition was quantified and characterized histologically. Biomechanical
      parameters were determined by the Very Low Rubber Hardness (VLRH) method and
      under confined compression stress relaxation. RESULTS: BMP-4/-7 treatment
      resulted in stronger collagen type-II staining and significantly enhanced
      glycosaminoglycan (GAG) deposition (3.2-fold; *P < 0.01) correlating with
      improved hardness (~1.7-fold; *P = 0.001) reaching 83% of native cartilage values
      after 28 days, a value not reached before 9 weeks without stimulation. LiCl
      treatment enhanced VLRH slightly, but significantly (~1.3-fold; *P = 0.016) with
      a trend to more ECM-deposition. BMP-4/-7 treatment significantly enhanced the E
      Modulus (105.7 +/- 34.1 kPa; *P = 0.000001) compared to controls (8.0 +/- 4.2
      kPa). Poisson's ratio was significantly improved by BMP-4/-7 treatment (0.0703 +/
      0.0409; *P = 0.013) vs controls (0.0432 +/- 0.0284) and a significantly lower
      permeability (5.8 +/- 2.1056 * 10(-14) m4/N.s; *P = 0.00001) was detected
      compared to untreated scaffolds (4.4 +/- 3.1289 * 10(-13) m4/N.s). CONCLUSIONS:
      While Wnt-activation is less effective, BMP-4/-7 heterodimer stimulation
      approximated native cartilage features in less than 50% of standard culture time
      representing a promising strategy for functional cartilage TE to improve
      biomechanical parameters of engineered cartilage.

PMID- 24280246
TI  - Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of
      the knee.
AB  - OBJECTIVE: To determine whether the structure of chondroitin sulfate (CS) in
      cartilage is reflected by the degree of cartilage degeneration in patients with
      osteoarthritis (OA) of the knee and to determine how CS biosynthesis affects
      cartilage degeneration. DESIGN: Two osteoarthritic cartilage samples were
      obtained from medial femoral condyle (MFC) and lateral femoral condyle (LFC) of
      24 knees with end-stage OA. The samples were assigned to two groups as follows:
      lesion and remote cartilage were adjacent to and remote from the osteoarthritic
      cartilage, respectively. Histological grade was determined according to the
      Mankin score. The CS concentration and chain length were determined using high
      performance liquid chromatography (HPLC) and gel filtration chromatography,
      respectively. Expression of the gene encoding CS glycosyltransferase was
      evaluated using a real-time quantitative polymerase chain reaction (qPCR) assay.
      These results were compared between lesion and remote cartilage. RESULTS: The
      Mankin score indicated that lesion cartilage was more degraded compared with
      remote cartilage. Although the CS levels varied among individuals, the mean CS
      concentration and chain length were significantly lower and shorter in lesion
      cartilage than in remote cartilage, respectively (concentration: 12.04 vs 14.84
      MUg/mg wet weight, P = 0.021; chain length: 5.36 vs 6.19 kDa, P = 0.026). Three
      genes encoding CS glycosyltransferases (CHPF, CSGALNACT1, CSGALNACT2) were
      expressed at lower levels in lesion cartilage. CONCLUSIONS: In the osteoarthritic
      knee, the CS concentration and chain length were reduced closer to the more
      degraded cartilage with decreasing CS glycosyltransferase gene expression.
      Inhibition of CS glycosyltransferase gene expression may reduce CS chain length,
      which may contribute to OA progression.

PMID- 24280247
TI  - Statins and fibrates do not affect development of spontaneous cartilage damage in
      STR/Ort mice.
AB  - OBJECTIVE: Since statins and fibrates are capable of improving the metabolic
      profile of patients as well as decreasing inflammation, they are considered as
      potential drugs for preventing osteoarthritis (OA). The goal of the present study
      was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse
      model. DESIGN: Male STR/Ort mice received control diet or control diet containing
      two different dosages of simvastatin or fenofibrate or a combination of both.
      Mice were euthanized after 16 weeks of treatment at the age of 24 weeks. Serum
      analysis for metabolic and inflammatory markers, histologic OA grading and micro
      computed tomography (MUCT) analysis of subchondral bone plate were performed.
      RESULTS: Simvastatin treatment did not have a statistically significant effect on
      any of the measured parameters. Fenofibrate treated mice gained less body weight
      (BW) and had lower serum amyloid A (SAA) levels, but higher Interleukin (IL)
      1alpha and MIP1alpha than other mice. Mice treated with 200 mg/kg BW/day
      fenofibrate had less subchondral bone plate volume than control, but no
      statistically significant reduction in cartilage damage. In the combination
      treatment group, BW and SAA were lower than control. Overall, bodyweight,
      synovium membrane cell layers and SAA levels correlated to subchondral bone plate
      changes and subchondral bone plate changes correlated to cartilage damage.
      CONCLUSIONS: Statins and fibrates did not affect development of cartilage damage
      in the STR/Ort spontaneous OA mouse model. Fenofibrates however, had an effect on
      BW, serum inflammation markers and subchondral bone plate morphology.

PMID- 24280248
TI  - Assessing the need for and acceptability of a free-of-charge postpartum HPV
      vaccination program.
AB  - OBJECTIVE: Human papillomavirus (HPV) vaccine uptake rate among young adult US
      women was only 23% in 2010. One way to improve this low rate is to administer the
      vaccine postpartum. We examined whether this population requires vaccination and
      whether they would be agreeable to receiving it free of charge after delivery.
      STUDY DESIGN: Women 26 years of age or younger seeking prenatal care in publicly
      funded clinics in southeast Texas were interviewed in 2012 regarding their HPV
      vaccination status, barriers to vaccination, and whether they would be willing to
      receive this vaccine postpartum if offered free of charge. Medical charts were
      reviewed to extract additional information. RESULTS: Overall, 13.0% (65 of 500)
      stated they had initiated and 7.6% (38 of 500) completed the 3-dose vaccine
      series. Ethnic differences were noted with 21.0% of non-Hispanic whites, 14.6% of
      blacks, and 9.3% of Hispanics (P = .002) initiating the vaccine and 13.5%, 7.8%,
      and 5.2% (P = .006) competing all 3 doses, respectively. Lowest initiation (4.2%)
      and completion (1.4%) rates were observed among recently immigrated Hispanic
      women. Those who had not graduated from high school and older women were less
      likely to have been vaccinated. Almost 83% of those who had not received any HPV
      doses or completed the series were willing to receive the injection free of
      charge in the hospital after their delivery. CONCLUSION: HPV vaccine uptake rates
      are very low among women receiving prenatal care in southeast Texas. Offering
      this vaccine free of charge to postpartum women could be an effective strategy in
      this population because 5 of 6 women favored receiving it in this setting.

PMID- 24280249
TI  - Hyperemesis gravidarum and long-term health of the offspring.
AB  - Nausea and vomiting of pregnancy is a very common occurrence, but the reported
      incidence of hyperemesis gravidarum (a more severe form of vomiting in pregnancy)
      is much lower, estimated to vary from 0.3-3.6%. Studies have shown that nausea
      and vomiting of pregnancy is associated with improved fetal outcomes, such as
      lower rates of miscarriage. However, there are limited data on outcomes
      associated with hyperemesis gravidarum, which have focused on pregnancy and
      neonatal outcomes. Recently, studies showed adverse health outcomes, such as a
      reduction in insulin sensitivity in childhood and increased incidence of
      psychological disorders in adulthood. The effects of hyperemesis gravidarum in
      the offspring need to be further examined throughout childhood, adolescence, and
      into adulthood, so that long-term disease risks can be evaluated. 

PMID- 24280250
TI  - Volvox, rolling out from under the shadow of Chlamydomonas with support from the
      AGA.

PMID- 24280251
TI  - Towards widespread noninvasive assessment of pulmonary vascular resistance in
      clinical practice.

PMID- 24280252
TI  - Bovine rabies in Turkey: patterns of infection and implications for costs and
      control.
AB  - The incidence of rabies in livestock is an important factor for estimating the
      economic impact of the disease, but obtaining reliable data is hindered by
      inadequate surveillance. In order to understand the contribution of livestock
      rabies to the overall burden of disease, the rabies incidence in cattle was
      investigated in detail for Turkey between 2008 and 2011. Data were compiled on
      cattle numbers, samples submitted for rabies diagnosis, vaccinated animals and
      positive rabies cases in animals for seven regions in Turkey. Rabies incidence in
      cattle fluctuated annually and differed between regions from 0.10 to 3.87
      cases/100 000 animals. The positive influence of compensation schemes was
      observed. Livestock losses were conservatively estimated at around $250 000
      international dollars per annum, although in areas where compensation schemes are
      not operating this could be an underestimate of the economic burden. Vaccination
      of cattle remains an option for disease prevention, although oral rabies
      vaccination through aerially distributed baits should be implemented to prevent
      the further spread of fox-mediated rabies, which could result in much greater
      economic costs.

PMID- 24280253
TI  - Multiple criteria for evaluating pollinator performance in highbush blueberry
      (Ericales: Ericaceae) agroecosystems.
AB  - Numerous bee species provide pollination services in agricultural ecosystems.
      Evaluating a pollinator's performance with regard to a crop is an important step
      in attributing pollination services and predicting how changes in a bee community
      or foraging environment will affect those services. We used multiple criteria to
      evaluate pollinators of North Carolina highbush blueberry, Vaccinium corymbosum
      L., agroecosystems. For five groups of bees (Apis mellifera L., Bombus spp.,
      Habropoda laboriosa F., small native bees, and Xylocopa virginica L.), we
      measured forager abundance through transect observations, quantified per-visit
      efficiency as viable seed set resulting from a single visit, and analyzed bee
      presence in different weather conditions. We also considered two other criteria
      affecting pollinator performance-visitation rate and interspecific influence. A.
      mellifera was the most abundant bee in the majority of our survey sites, yet had
      low per-visit efficiency and reduced foraging activity in inclement weather.
      Small native bees were highly efficient pollinators. Their visits resulted in
      nearly twice as many seeds as A. mellifera or H. laboriosa. Bombus spp., H.
      laboriosa, and small native bees were more resilient to fluctuations in
      temperature, wind speed, and solar radiation than A. mellifera. Although nectar
      robbing X. virginica contributed to little pollination through direct flower
      visits, their presence within the crop impacts the behavior and performance of
      other individuals. Underscoring the importance of evaluating pollinator
      performance via multiple criteria, our results show that bee groups contribute to
      pollination in different ways. These differences may provide functional
      complementarity and stability of pollination services to agricultural systems. 

PMID- 24280254
TI  - The role of Bergmann glial cells in cerebellar development.

PMID- 24280255
TI  - The S-Connect study: results from a randomized, controlled trial of Souvenaid in
      mild-to-moderate Alzheimer's disease.
AB  - INTRODUCTION: Souvenaid(r) containing Fortasyn(r) Connect is a medical food
      designed to support synapse synthesis in persons with Alzheimer's disease (AD).
      Fortasyn Connect includes precursors (uridine monophosphate; choline;
      phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors
      (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal
      membranes. Whether Souvenaid slows cognitive decline in treated persons with mild
      to-moderate AD has not been addressed. METHODS: In a 24-week, double-masked
      clinical trial at 48 clinical centers, 527 participants taking AD medications
      [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini
      Mental State Examination score 19.5 (SD = 3.1, range 14-24)] were randomized 1:1
      to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an
      iso-caloric control. The primary outcome of cognition was assessed by the 11-item
      Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance
      was calculated from daily diary recordings of product intake. Statistical
      analyses were performed using mixed models for repeated measures. RESULTS:
      Cognitive performance as assessed by ADAS-cog showed decline over time in both
      control and active study groups, with no significant difference between study
      groups (difference =0.37 points, Standard Error, SE = 0.57, p = 0.513). No group
      differences in adverse event rates were found and no clinically relevant
      differences in blood safety parameters were noted. Overall compliance was high
      (94.1% [active] and 94.5% [control]), which was confirmed by significant changes
      in blood (nutritional) biomarkers. CONCLUSIONS: Add-on intake of Souvenaid during
      24 weeks did not slow cognitive decline in persons treated for mild-to-moderate
      AD. Souvenaid was well tolerated in combination with standard care AD
      medications. TRIAL REGISTRATION: DUTCH TRIAL REGISTER NUMBER: NTR1683.

PMID- 24280256
TI  - Reproductive toxicity on female mice induced by microcystin-LR.
AB  - There are increasing concerns about health risk of human exposure to microcystin
      LR (MC-LR) over the past few decades. Nevertheless, its female mammalian
      reproductive toxicity has not been addressed yet. In the present study, we
      firstly reported MC-LR could impact female reproductive function of mammals.
      After 28 days MC-LR exposure, relative ovary weight significantly reduced in 20
      MUg/kg MC-LR group and this reduction may be relative with pathomorphological
      changes of ovary. The result of histological evaluation of follicles showed that
      primordial follicles decreased roughly in half at high dose level compared with
      control. Since serum hormone assay indicated that MC-LR induced decrease of
      progesterone but not FSH or LH, disturbance of estrus cycle was seemed to result
      from direct impact of ovary rather than indirectly from hypothalamus or
      pituitary. As expected, MC-LR was detected in the ovaries of MC-LR exposure mice
      by immunoblot analysis.

PMID- 24280257
TI  - Identification of genes regulating growth and fatness traits in pig through
      hypothalamic transcriptome analysis.
AB  - Previous studies on Iberian * Landrace (IBMAP) pig intercrosses have enabled the
      identification of several quantitative trait locus (QTL) regions related to
      growth and fatness traits; however, the genetic variation underlying those QTLs
      are still unknown. These traits are not only relevant because of their impact on
      economically important production traits, but also because pig constitutes a
      widely studied animal model for human obesity and obesity-related diseases. The
      hypothalamus is the main gland regulating growth, food intake, and fat
      accumulation. Therefore, the aim of this work was to identify genes and/or gene
      transcripts involved in the determination of growth and fatness in pig by a
      comparison of the whole hypothalamic transcriptome (RNA-Seq) in two groups of
      phenotypically divergent IBMAP pigs. Around 16,000 of the ~25.010 annotated genes
      were expressed in these hypothalamic samples, with most of them showing
      intermediate expression levels. Functional analyses supported the key role of the
      hypothalamus in the regulation of growth, fat accumulation, and energy
      expenditure. Moreover, 58,927 potentially new isoforms were detected. More than
      250 differentially expressed genes and novel transcript isoforms were identified
      between the two groups of pigs. Twenty-one DE genes/transcripts that colocalized
      in previously identified QTL regions and/or whose biological functions are
      related to the traits of interest were explored in more detail. Additionally, the
      transcription factors potentially regulating these genes and the subjacent
      networks and pathways were also analyzed. This study allows us to propose strong
      candidate genes for growth and fatness based on expression patterns, genomic
      location, and network interactions. 

PMID- 24280259
TI  - Treatment of palmoplantar pustulosis with ustekinumab--the importance of
      interfering with the IL23/Th17 pathway.

PMID- 24280258
TI  - Contribution of CBX4 to cumulus oophorus cell phenotype in mice and attendant
      effects in cumulus cell cloned embryos.
AB  - Cumulus oophorus cells play an essential role in oocyte development. They are
      also widely employed as donor cells for cloning by somatic cell nuclear transfer.
      Our previous studies revealed that Cbx4 mRNA was overexpressed in cloned two-cell
      embryos. These data indicated that CBX4 may regulate normal cumulus cell
      differentiation and that its overexpression in clones could contribute to
      aberrant gene regulation. We used siRNA-mediated knockdown of Cbx4 to assess its
      role in determining cumulus cell phenotype and compared the effects of this
      knockdown to published data for aberrant gene regulation in cloned embryos. We
      observed widespread effects on the expression of genes related to diverse
      processes in cultured cumulus cells, including cell assembly/proliferation and
      DNA replication/repair, endocrine function, carbohydrate and lipid metabolism,
      inflammation, and cell morphology, with apparent effects of CBX4 in promoting
      cumulus cell proliferation and survival and inhibiting differentiation. Overall,
      the data implicate CBX4 as a key component in the pathway integrating endocrine
      signals, intraovarian paracrine factors, and oocyte-derived factors in the
      control of cumulus cell functions. We also observed altered expression of 25
      cumulus cell markers of oocyte quality, indicating an important role of CBX4 in
      production of high quality oocytes. Finally, we found that about one-quarter of
      the genes showing aberrant transcription in cloned embryos are sensitive to Cbx4
      knockdown in cumulus cells, consistent with a role for aberrant Cbx4 regulation
      in elaborating abnormal cloned embryo characteristics. 

PMID- 24280261
TI  - Intradermal photosensitisation facilitates stimulation of MHC class-I restricted
      CD8 T-cell responses of co-administered antigen.
AB  - The protection or treatment of several immunological disorders is dependent on
      the antigen-specific and cytotoxic CD8 T cells. However, vaccines aimed at
      stimulating CD8 T-cell responses are typically ineffective because vaccine
      antigens are primarily processed by the MHC class-II and not the MHC class-I
      pathway of antigen presentation: the latter requires cytosolic delivery of
      antigen. In order to facilitate targeting of antigen to cytosol, the antigen was
      combined with the photosensitiser TPCS2a (disulfonated tetraphenyl chlorin) and
      administered intradermally to mice. The photosensitiser was activated by
      illumination of the injection site. This photochemical internalization (PCI)
      strongly increased the stimulation of CD8 T-cell responses as measured by antigen
      specific proliferation and secretion of pro-inflammatory cytokines. Fluorescence
      microscopy showed that delivery to cytosol was TPCS2a dependent and occurred by
      light-induced disruption of TPCS2a- and antigen-containing endosomes. PCI-based
      vaccination prevented growth of malignant B16 cells as compared with vaccination
      without PCI. In conclusion, PCI represents a potent tool for delivery of antigens
      to cytosol for stimulation of cytotoxic CD8 T-cell responses. This study
      demonstrated a first proof-of-principle for PCI-mediated immunisation with
      potential application in cancer immunotherapy. 

PMID- 24280260
TI  - Hyaluronic acid derivative-coated nanohybrid liposomes for cancer imaging and
      drug delivery.
AB  - Nanohybrid liposomes coated with amphiphilic hyaluronic acid-ceramide (HACE) was
      fabricated for targeted delivery of anticancer drug and in vivo cancer imaging.
      Nanohybrid liposomes including doxorubicin (DOX) and Magnevist, a contrast agent
      for magnetic resonance (MR) imaging, with 120-130nm mean diameter and a narrow
      size distribution were developed. DOX release from the developed formulation was
      improved at acidic pH (pH5.5 and 6.8) versus physiological pH (pH7.4).
      Cytotoxicity induced by the blank plain liposome was reduced by coating the outer
      surface of the nanohybrid liposome with HACE. Cellular uptake of DOX from the
      nanohybrid liposome was enhanced by HA and CD44 receptor interaction, versus the
      plain liposome. In vivo contrast-enhancing effects revealed that the nanohybrid
      liposome can be used as a tumor targeting MR imaging probe for cancer diagnosis.
      In a pharmacokinetic study in rats, in vivo clearance of DOX was decreased in the
      order DOX solution, plain liposome (F2), and nanohybrid liposome (F3), indicating
      prolonged circulation of the drug in the blood stream and improved therapeutic
      efficacy of the nanohybrid liposome (F3). Based on these findings, the nanohybrid
      liposomal system may be a useful candidate for real-time cancer diagnosis and
      therapy. 

PMID- 24280262
TI  - Unmodified drug used as a material to construct nanoparticles: delivery of
      cisplatin for enhanced anti-cancer therapy.
AB  - The poor solubility of cisplatin (CDDP) often presents a major obstacle in the
      formulation of CDDP in nanoparticles (NPs) by traditional methods. We have
      developed a novel method for synthesizing CDDP NPs taking advantage of its poor
      solubility. By mixing two reverse microemulsions containing KCl and a highly
      soluble precursor of CDDP, cis-diaminedihydroplatinum (II), we have successfully
      formulated CDDP NPs with a controllable size (in the range of 12-75nm) and high
      drug loading capacity (approximately 80wt.%). The formulation was done in two
      steps. The pure CDDP NPs were first stabilized for dispersion in an organic
      solvent by coating with 1, 2-dioleoyl-sn-glycero-3-phosphate (DOPA). Both x-ray
      photoelectron spectroscopy and (1)H NMR data confirmed that the major ingredient
      of the DOPA-coated NPs was CDDP. After purification, additional lipids were added
      to stabilize the NPs for dispersion in an aqueous solution. The final NPs contain
      a lipid bilayer coating and are named Lipid-Pt-Cl (LPC) NPs, which showed
      significant antitumor activity both in vitro and in vivo. Thus, CDDP precipitate
      serves as the major material for assembling the novel NPs. This unique method of
      nanoparticle synthesis may be applicable in formulating other insoluble drugs. 

PMID- 24280263
TI  - The prognostic role of serum total bilirubin in non-ST segment elevation
      myocardial infarction: what about on-admission cardiovascular medications?

PMID- 24280264
TI  - Circadian blood pressure variation in normotensive patients with panic disorder.
AB  - Nondipper pattern of blood pressure (BP) is associated with cardiovascular risk.
      In this study, we compared dipper versus nondipper patterns between normotensive
      patients with panic disorder (PD) and a control group. A total of 25 normotensive
      patients with PD and 25 controls were enrolled. Twenty-four-hour ambulatory BP
      monitoring was performed in all patients. At least 10% of sleep-related nocturnal
      decrease in systolic and diastolic BP was accepted as dipper status, while
      decreases <10% were defined as a nondipper. Patients with PD had significantly
      higher incidence of nondipper BP pattern than controls. The reduction of
      nighttime BP in both systolic and diastolic and mean BP was significantly lower
      in patients with PD than in the control group (7.6% +/- 4.3% vs 13% +/- 3.9%, P <
      .001; 11% +/- 7% vs 15% +/- 5%, P = .004; 9% +/- 5% vs 14% +/- 4%, P = .002,
      respectively). Panic disorder is associated with nondipper BP pattern, causing
      impaired circadian BP in normotensive settings. 

PMID- 24280265
TI  - Low high-density lipoprotein cholesterol is characterized by elevated oxidative
      stress.
AB  - High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for
      premature atherosclerosis and cardiovascular disease. Plasma HDL exerts potent
      antioxidant activity. We evaluated parameters associated with oxidative stress in
      participants with low HDL-C. This study included 32 patients with low HDL-C (<=35
      mg/dL) and 33 age- and sex-matched control patients with normal HDL-C (>35
      mg/dL). We evaluated clinical and laboratory parameters that are associated with
      oxidative stress. The oxidative stress index (OSI) levels were significantly
      higher in the low HDL-C group (3.32 [0.01-13.3] vs 0.74 [0.17-3.55] AU; P<.01)
      and negatively correlated with HDL-C levels. We suggest that change in OSI and
      uric acid levels in the study group might indicate increased oxidative status in
      patients with low HDL-C. This may be associated with increased cardiovascular
      risk.

PMID- 24280266
TI  - Impaired renal function in stroke patients with atrial fibrillation.
AB  - BACKGROUND: Stroke patients with atrial fibrillation (AF) are prone to have
      comorbidities such as impaired renal function. Because poly-pharmacotherapy is
      often required in those patients, renal function is important to consider in
      light of renally cleared medications such as direct oral anticoagulants. In this
      study, we analyzed frequency and predictors for impaired renal function and its
      impact on functional outcome in stroke patients with underlying AF. METHODS: We
      analyzed 272 patients with acute ischemic stroke and AF of our prospective,
      observational stroke database. Estimated glomerular filtration rate (eGFR) was
      calculated on admission and during hospitalization from the equation of the
      Modification Diet for Renal Disease. Outcome measures included mortality and
      functional outcome at 90 days, assessed as modified Rankin Scale (mRS) score.
      RESULTS: On admission, impaired renal function was found in 41.5% (n = 113) and
      was associated with worse 90-day outcome (mRS score <= 2: 26.5% versus 45.9%, P =
      .001) and a higher mortality rate (23.9% versus 14.5%, P = .043). Multivariate
      logistic regression identified older age and history of myocardial infarction as
      independent predictors of renal dysfunction on admission (P < .05). Normalization
      of eGFR during hospitalization was achieved in 55.8%. CONCLUSIONS: In patients
      with acute ischemic stroke and AF, impaired renal function on admission is
      frequent and associated with worse outcome. Normalization of eGFR can often be
      achieved during hospitalization, but in everyday life, fluctuations of renal
      function because of infection or dehydration have to be considered. Careful
      monitoring of renal status is indispensable and should influence drug treatment
      decisions.

PMID- 24280267
TI  - Lipid levels are regionally associated with cerebral microbleeds in patients with
      intracerebral hemorrhage.
AB  - BACKGROUND: Lipid levels may be involved in intracerebral hemorrhage (ICH)
      etiology, which suggested that lipid levels may be associated with the etiology
      of microbleeds (MBs) in patients with ICH. To explore this, we examined the
      association between lipid levels and MBs in different cerebral regions in
      patients with ICH. METHODS: Patients admitted to our hospital with ICH were
      consecutively and prospectively included. Demographic and clinical information
      were collected and analyzed according to the occurrence and location of MBs and
      levels of triglycerides (TGs). RESULTS: Of the 77 patients included in our study,
      63 (81.8%) were found to have MBs. Prevalence of MBs in the "deep or
      infratentorial" region and any region increased with increasing tercile in TG
      concentration; however, no such trend was observed for strictly lobar MBs. The
      odds ratio (OR) for occurrence of MBs in deep or infratentorial region was even
      higher for the third tercile relative to the first: 6.77 (95% confidence interval
      [CI] 1.31-34.96). The OR for occurrence of MB in any region was even higher for
      the third tercile relative to the first: 12.24 (95% CI 1.40-106.83). However, the
      OR for occurrence of deep or infratentorial region and any region in the second
      tercile relative to the first tercile did not reach significance. Moreover, TG
      levels did not appear to be associated with the occurrence of strictly lobar MBs.
      CONCLUSIONS: High TGs were associated with deep or infratentorial and any MBs but
      not with lobar MBs. This finding may shed light on the role of lipids in MB and
      ICH etiology.

PMID- 24280268
TI  - The beneficial effects of reduced magnesium during the oocyte-to-embryo
      transition are conserved in mice, domestic cats and humans.
AB  - In many cell types Mg2+ can antagonise Ca2+ -stimulated signalling pathways, but
      information regarding the effects of these ions on IVF and subsequent embryonic
      development is limited. Our objectives were to evaluate the effects of Mg2+ in
      the IVF medium on embryonic development in mice and then determine if similar
      effects occurred in domestic cats and humans. Oocytes from hybrid and outbred
      mice, domestic cats and humans were fertilised (IVF, mice and cats;
      intracytoplasmic sperm injection (ICSI), humans) in the presence of 0.2 or 1.2
      (mouse and human) or 1.0 (cat) mM Mg2+ and the resulting embryos were cultured to
      the blastocyst stage. Decreased concentrations of Mg2+ during IVF increased
      (P<0.05) cleavage of oocytes from outbred mice (77.9 vs. 51.0%), development of
      embryos from hybrid mice (74.5 vs. 51.0% hatching blastocyst per cleaved embryo)
      and both cleavage (68.4 vs. 46.8%) and blastocyst development (53.0 vs. 26.2% per
      cleaved embryo) in cats. Development to the blastocyst stage (52.1 vs. 40.2%) was
      also improved (P<0.05) when ICSI was performed on human oocytes in the presence
      of 0.2 mM Mg2+, compared with a commercial culture medium. Sensitivity to
      increased (1.0 to 1.2 mM) concentrations of Mg2+ in the medium during the oocyte
      to-embryo transition appears to be conserved in three different species.

PMID- 24280269
TI  - Isolation of a novel mutant gene for soil-surface rooting in rice (Oryza sativa
      L.).
AB  - BACKGROUND: Root system architecture is an important trait affecting the uptake
      of nutrients and water by crops. Shallower root systems preferentially take up
      nutrients from the topsoil and help avoid unfavorable environments in deeper soil
      layers. We have found a soil-surface rooting mutant from an M2 population that
      was regenerated from seed calli of a japonica rice cultivar, Nipponbare. In this
      study, we examined the genetic and physiological characteristics of this mutant.
      RESULTS: The primary roots of the mutant showed no gravitropic response from the
      seedling stage on, whereas the gravitropic response of the shoots was normal.
      Segregation analyses by using an F2 population derived from a cross between the
      soil-surface rooting mutant and wild-type Nipponbare indicated that the trait was
      controlled by a single recessive gene, designated as sor1. Fine mapping by using
      an F2 population derived from a cross between the mutant and an indica rice
      cultivar, Kasalath, revealed that sor1 was located within a 136-kb region between
      the simple sequence repeat markers RM16254 and 2935-6 on the terminal region of
      the short arm of chromosome 4, where 13 putative open reading frames (ORFs) were
      found. We sequenced these ORFs and detected a 33-bp deletion in one of them,
      Os04g0101800. Transgenic plants of the mutant transformed with the genomic
      fragment carrying the Os04g0101800 sequence from Nipponbare showed normal
      gravitropic responses and no soil-surface rooting. CONCLUSION: These results
      suggest that sor1, a rice mutant causing soil-surface rooting and altered root
      gravitropic response, is allelic to Os04g0101800, and that a 33-bp deletion in
      the coding region of this gene causes the mutant phenotypes.

PMID- 24280270
TI  - Mapping a quantitative trait locus for resistance to bacterial grain rot in rice.
AB  - BACKGROUND: Bacterial grain rot (BGR), caused by the bacterial pathogen
      Burkholderia glumae, is a destructive disease of rice. Because BGR tends to be
      highly affected by environmental conditions such as temperature and humidity, it
      is difficult to evaluate BGR resistance of diverse cultivars with different
      heading dates by using field inoculation. Molecular tagging of genes involved in
      BGR is an important objective for rice breeding. RESULTS: In this study, we
      mapped a quantitative trait locus (QTL) for BGR resistance by a modified cut
      panicle inoculation method. First, we assessed the levels of BGR resistance in 84
      cultivars by a standard cut-panicle inoculation technique, in which panicles are
      harvested and inoculated in the laboratory under controlled conditions. For the
      genetic analysis, we selected two cultivars: Kele, a resistant traditional
      lowland cultivar (indica) that originated in India, and Hitomebore, a susceptible
      modern lowland cultivar (temperate japonica) from Japan. Second, by comparing the
      susceptibility of Kele and Hitomebore spikelets before and up to 3 days after
      anthesis, we found a dramatic decline in susceptibility at 1 day after anthesis
      in Kele but not in Hitomebore. Thus, we applied a modified method by inoculating
      spikelets at 1 day after anthesis for further analysis. To search for QTLs
      associated with BGR resistance, we measured the ratio of diseased spikelets (RDS,
      an index reflecting both quantity and severity of infection) and the ratio of
      diseased spikelet area (RDSA) in 110 backcrossed inbred lines (BILs) derived from
      a cross between Kele and Hitomebore. One major QTL associated with both RDS and
      RDSA was detected on the long arm of chromosome 1. This QTL explained 25.7% and
      12.1% of the total phenotypic variance in RDS and RDSA in the BILs, respectively,
      and the Kele allele increased BGR resistance. CONCLUSIONS: We mapped a major QTL
      for BGR resistance on the long arm of chromosome 1. These results clearly
      demonstrated that genetic analysis of BGR resistance in rice can be effectively
      performed and that this trait could be a target of marker-assisted selection in
      rice breeding programs.

PMID- 24280271
TI  - Novel clathrin/actin-based endocytic machinery associated with junction turnover
      in the seminiferous epithelium.
AB  - Tubulobulbar complexes are elaborate clathrin/actin related structures that form
      at sites of intercellular attachment in the seminiferous epithelium of the
      mammalian testis. Here we summarize what is currently known about the morphology
      and molecular composition of these structures and review evidence that the
      structures internalize intercellular junctions both at apical sites of Sertoli
      cell attachment to spermatids, and at basal sites where Sertoli cells form the
      blood-testis barrier. We present updated models of the sperm release and
      spermatocyte translocation mechanisms that incorporate tubulobulbar complexes
      into their designs. 

PMID- 24280272
TI  - Single-center experience with botulinum toxin endoscopic detrusor injection for
      the treatment of congenital neuropathic bladder in children: effect of dose
      adjustment, multiple injections, and avoidance of reconstructive procedures.
AB  - OBJECTIVE: Since 2007, intra-detrusor OnabotulinumtoxinA (OnabotA) injections
      have been selectively offered at our institution for cases in which maximal
      anticholinergic therapy failed or was not tolerated. Herein we present our
      experience with this approach. MATERIALS AND METHODS: We prospectively obtained
      data on 17 patients who underwent OnabotA injections over a 4-year period.
      Demographic information, number of injections, and dose delivered were captured.
      Children were monitored with baseline and post-injection renal ultrasound,
      urodynamics, and assessed for side effects, satisfaction, and symptom
      improvement. RESULTS: Forty-three sessions were performed with injections given
      every ~ 6 months. Mean patient age was 10.7 years (range, 3-17). Compared with
      baseline, after the first injection, mean bladder capacity adjusted for age and
      compliance improved by 27% (p = 0.039) and 45.2% (p = 0.041), respectively. After
      subsequent injections, these values increased to 35.7% (p = 0.043) and 55.1% (p =
      0.091), respectively. Out of 13 symptomatic patients, >= 50% improvement was
      reported in ten (76.9%) and complete resolution in seven (53.8%). However, all
      three patients in whom the maximum dose of OnabotA was reduced from 300 to 200
      units complained of recurrent symptoms. Fourteen children avoided surgical
      reconstruction as a second line of treatment. Overall patient/parental reported
      satisfaction rate was 70.6% (12/17). CONCLUSIONS: Intra-detrusor OnabotA
      injection is a promising intervention for management of neuropathic bladder in
      selected patients. Our data demonstrate improvement in symptoms and urodynamic
      parameters. Although an optimal dose has not been determined for children, we
      found optimal response with a maximum administration of OnabotA up to 300 units.

PMID- 24280273
TI  - Impact of biochemical design on estrogen receptor/estrogen response element
      interaction by surface plasmon resonance technology.
AB  - The estrogen receptor (ER) is a transcription factor that binds under 17-beta
      estradiol (E2) stimulation as homodimer to a short DNA consensus sequence named
      estrogen response element (ERE). The ER/ERE interaction has been assessed by
      several research groups through different methodologies notably by surface
      plasmon resonance (SPR) techniques. The biochemical parameters and conditions
      (solvent, ER concentration, salt, time and temperature) used to prepare samples
      before analysis were very different from one study to another. But no studies
      have aimed to compare the effect of these modifications on ER/ERE interaction.
      Therefore the main objective of the present paper was to assess the influence of
      biochemical parameters onto the ER/ERE interaction with the final aim to improve
      the comprehension of this interaction. Our results highlighted that parameters
      like solvent, ER concentration, salt and surfactant concentration, temperature
      and time deeply modify ER/ERE interaction. Nevertheless, the dimer formation
      under E2 stimulation occurred with all tested conditions. Altogether, incubation
      parameters of ER with E2, deeply modify its binding level onto ERE. These data
      constitute an important key point to consider for the improvement of ER/ERE
      detection method depending upon the aim of the study (interaction measurement,
      environmental detection, development of new technologies or devices).

PMID- 24280274
TI  - Catalase in peroxidase clothing: Interdependent cooperation of two cofactors in
      the catalytic versatility of KatG.
AB  - Catalase-peroxidase (KatG) is found in eubacteria, archaea, and lower eukaryotae.
      The enzyme from Mycobacterium tuberculosis has received the greatest attention
      because of its role in activation of the antitubercular pro-drug isoniazid, and
      the high frequency with which drug resistance stems from mutations to the katG
      gene. Generally, the catalase activity of KatGs is striking. It rivals that of
      typical catalases, enzymes with which KatGs share no structural similarity.
      Instead, catalatic turnover is accomplished with an active site that bears a
      strong resemblance to a typical peroxidase (e.g., cytochrome c peroxidase). Yet,
      KatG is the only member of its superfamily with such capability. It does so using
      two mutually dependent cofactors: a heme and an entirely unique Met-Tyr-Trp (MYW)
      covalent adduct. Heme is required to generate the MYW cofactor. The MYW cofactor
      allows KatG to leverage heme intermediates toward a unique mechanism for H2O2
      oxidation. This review evaluates the range of intermediates identified and their
      connection to the diverse catalytic processes KatG facilitates, including
      mechanisms of isoniazid activation. 

PMID- 24280276
TI  - Why do older people oppose physician-assisted dying? A qualitative study.
AB  - BACKGROUND: Physician-assisted dying at the end of life has become a significant
      issue of public discussion. While legally available in a number of countries and
      jurisdictions, it remains controversial and illegal in New Zealand. AIM: The
      study aimed to explore the reasons some healthy older New Zealanders oppose
      physician-assisted dying in order to inform current debate. DESIGN: Recorded
      interviews were transcribed and analysed by the authors after some edits had been
      made by respondents. SETTING/PARTICIPANTS: In all, 11 older participants (over 65
      years) who responded to advertisements placed in Grey Power magazines and a
      University of Auckland email list were interviewed for around 1 h and asked a
      number of open-ended questions. RESULTS: Four central themes opposing physician
      assisted dying were identified from the interviews: one's personal experience
      with health care and dying and death, religious reasoning and beliefs, slippery
      slope worries and concern about potential abuses if physician-assisted dying were
      legalised. CONCLUSIONS: An important finding of the study suggests that how some
      older individuals think about physician-assisted dying is strongly influenced by
      their past experiences of dying and death. While some participants had witnessed
      good, well-managed dying and death experiences which confirmed for them the view
      that physician-assisted dying was unnecessary, those who had witnessed poor dying
      and death experiences opposed physician-assisted dying on the grounds that such
      practices could come to be abused by others.

PMID- 24280275
TI  - Nanoparticulate flurbiprofen reduces amyloid-beta42 generation in an in vitro
      blood-brain barrier model.
AB  - INTRODUCTION: The amyloid-beta42 (Abeta42) peptide plays a crucial role in the
      pathogenesis of Alzheimer's disease (AD), the most common neurodegenerative
      disorder affecting the elderly. Over the past years, several approaches and
      compounds developed for the treatment of AD have failed in clinical studies,
      likely in part due to their low penetration of the blood-brain barrier (BBB).
      Since nanotechnology-based strategies offer new possibilities for the delivery of
      drugs to the brain, this technique is studied intensively for the treatment of AD
      and other neurological disorders. METHODS: The Abeta42 lowering drug flurbiprofen
      was embedded in polylactide (PLA) nanoparticles by emulsification-diffusion
      technique and their potential as drug carriers in an in vitro BBB model was
      examined. First, the cytotoxic potential of the PLA-flurbiprofen nanoparticles on
      endothelial cells and the cellular binding and uptake by endothelial cells was
      studied. Furthermore, the biological activity of the nanoparticulate flurbiprofen
      on gamma-secretase modulation as well as its in vitro release was examined.
      Furthermore, the protein corona of the nanoparticles was studied as well as their
      ability to transport flurbiprofen across an in vitro BBB model. RESULTS: PLA
      flurbiprofen nanoparticles were endocytosed by endothelial cells and neither
      affected the vitality nor barrier function of the endothelial cell monolayer. The
      exposure of the PLA-flurbiprofen nanoparticles to human plasma occurred in a
      rapid protein corona formation, resulting in their decoration with bioactive
      proteins, including apolipoprotein E. Furthermore, luminally administered PLA
      flurbiprofen nanoparticles in contrast to free flurbiprofen were able to modulate
      gamma-secretase activity by selectively decreasing Abeta42 levels in the
      abluminal compartment of the BBB model. CONCLUSIONS: In this study, we were able
      to show that flurbiprofen can be transported by PLA nanoparticles across an in
      vitro BBB model and most importantly, the transported flurbiprofen modulated
      gamma-secretase activity by selectively decreasing Abeta42 levels. These results
      demonstrate that the modification of drugs via embedding in nanoparticles is a
      promising tool to facilitate drug delivery to the brain, which enables future
      development for the treatment of neurodegenerative disorders like AD.

PMID- 24280277
TI  - The Paediatric Palliative Screening Scale: Further validity testing.
AB  - BACKGROUND: Paediatric palliative care is still often introduced late in the
      illness trajectory of children with life-limiting diseases. Translating
      palliative care into practice continues to be a challenge. AIM: To validate the
      Paediatric Palliative Screening Scale further by defining attributes that predict
      the need for palliative care in children between 1 and 18 years. DESIGN:
      Proportional-odds logistic regression analysis was performed to investigate the
      relationship between the attributes of the Paediatric Palliative Screening Scale
      and the experts' assessment of case vignettes with various combinations of
      different attribute characteristics. Estimates from regression analysis were
      transformed to empirical weightings of the Paediatric Palliative Screening Scale
      attribute characteristics. SETTING/PARTICIPANTS: Online questionnaires with case
      vignettes were sent to 33 paediatric palliative care experts from Europe, the
      United States, Canada, Australia and New Zealand. RESULTS: The highest weightings
      among the five previously defined attributes were estimated life expectancy <12
      months (40% of maximum score) and preferences of the child/parents received
      (24%). Trajectory of disease and impact on daily activities of the child,
      expected outcome of treatment directed at the disease and burden of treatment,
      and symptom or problem burden were weighted less. CONCLUSIONS: According to this
      second step of psychometric testing of the Paediatric Palliative Screening Scale,
      the strongest and most urgent necessity indicators for a palliative care approach
      are life expectancy and child/family preferences. These results are somewhat
      discrepant with results from the previous validation of the instrument as well as
      previous research findings.

PMID- 24280278
TI  - Vitamin D deficiency as a cause of chronic pain in the palliative medicine
      clinic: two case reports.
AB  - BACKGROUND: Vitamin D deficiency is common in the general population and has been
      implicated as a cause of chronic pain. The palliative care population has a
      number of risk factors for vitamin D deficiency. We present two cases of
      unexplained pain in patients attending the palliative medicine outpatient clinic
      that improved after vitamin D replacement. CASES: Case 1 is a 46-year-old man
      with thalassaemia intermedia and back and leg pain without a clear cause. Case 2
      is a 28-year-old woman undergoing treatment for cervical cancer whose initial
      disease and treatment-related abdominal pain resolved but subsequently reported
      ongoing non-specific aches and pains. Case management: Both patients were found
      to have vitamin D levels <50 nmol/L and were treated with vitamin D replacement
      therapy. Case outcome: Following vitamin D replacement therapy, pain resolved in
      both patients allowing a reduction in analgesic therapy. CONCLUSIONS: The
      prevalence of vitamin D deficiency in the palliative care population merits
      further investigation, since these patients are at high risk of deficiency.
      Having an index of suspicion, particularly in those patients with known risk
      factors and pain that is not fully explained, may result in better pain control
      and functional outcomes.

PMID- 24280279
TI  - Improvement of antibody responses by HIV envelope DNA and protein co
      immunization.
AB  - BACKGROUND: Developing HIV envelope (Env) vaccine components that elicit durable
      and protective antibody responses is an urgent priority, given the results from
      the RV144 trial. Optimization of both the immunogens and vaccination strategies
      will be needed to generate potent, durable antibodies. Due to the diversity of
      HIV, an effective Env-based vaccine will most likely require an extensive
      coverage of antigenic variants. A vaccine co-delivering Env immunogens as DNA and
      protein components could provide such coverage. Here, we examine a DNA and
      protein co-immunization strategy by characterizing the antibody responses and
      evaluating the relative contribution of each vaccine component. METHOD: We co
      immunized rabbits with representative subtype A or B HIV gp160 plasmid DNA plus
      Env gp140 trimeric glycoprotein and compared the responses to those obtained with
      either glycoprotein alone or glycoprotein in combination with empty vector.
      RESULTS: DNA and glycoprotein co-immunization was superior to immunization with
      glycoprotein alone by enhancing antibody kinetics, magnitude, avidity, and
      neutralizing potency. Importantly, the empty DNA vector did not contribute to
      these responses. Humoral responses elicited by mismatched DNA and protein
      components were comparable or higher than the responses produced by the matched
      vaccines. CONCLUSION: Our data show that co-delivering DNA and protein can
      augment antibodies to Env. The rate and magnitude of immune responses suggest
      that this approach has the potential to streamline vaccine regimens by inducing
      higher antibody responses using fewer vaccinations, an advantage for a successful
      HIV vaccine design.

PMID- 24280281
TI  - Immunogenicity of highly conserved recombinant VacJ outer membrane lipoprotein of
      Pasteurella multocida.
AB  - Bacterial lipoproteins are emerging targets for inducing protective immunity
      against many infectious diseases. VacJ is a highly conserved and widely
      distributed outer membrane lipoprotein of Pasteurella multocida strains, which
      are known to affect a wide range of domestic as well as wild animals and birds.
      In the present study, the gene encoding for mature VacJ outer membrane
      lipoprotein of P. multocida serogroup B:2 strain P52 was cloned and over
      expressed in Escherichia coli as a fusion protein. The purified recombinant VacJ
      protein (~44kDa) was used for immunizing mice (6/group) along with adjuvants (FCA
      and alum) in two experiments. Immunization of mice with rVacJ (30MUg and
      75MUg/mice) elicited humoral immune response with significant (P<0.01) rise in
      antigen-specific titers of IgG and its subtypes (IgG1 and IgG2a). No protection
      was noticed in mice immunized with rVacJ (30MUg) along with FCA followed by
      challenge with 100 LD50 of the homologous strain. On the contrary, higher rVacJ
      dose (75MUg) along with FCA and alum provided 66.7% and 50% protection
      respectively, at reduced challenge dose (8 LD50). The study indicated that a
      lipidated recombinant VacJ lipoprotein with suitable adjuvants could potentially
      act as candidate antigen for vaccine development against pasteurellosis in
      livestock. 

PMID- 24280280
TI  - A global perspective of vaccination of healthcare personnel against measles:
      systematic review.
AB  - Measles transmission has been well documented in healthcare facilities.
      Healthcare personnel who are unvaccinated and who lack other evidence of measles
      immunity put themselves and their patients at risk for measles. We conducted a
      systematic literature review of measles vaccination policies and their
      implementation in healthcare personnel, measles seroprevalence among healthcare
      personnel, measles transmission and disease burden in healthcare settings, and
      impact/costs incurred by healthcare facilities for healthcare-associated measles
      transmission. Five database searches yielded 135 relevant articles; 47 additional
      articles were found through cross-referencing. The risk of acquiring measles is
      estimated to be 2 to 19 times higher for susceptible healthcare personnel than
      for the general population. Fifty-three articles published worldwide during 1989
      2013 reported measles transmission from patients to healthcare personnel; many of
      the healthcare personnel were unvaccinated or had unknown vaccination status.
      Eighteen articles published worldwide during 1982-2013 described examples of
      transmission from healthcare personnel to patients or to other healthcare
      personnel. Half of European countries have no measles vaccine policies for
      healthcare personnel. There is no global policy recommendation for the
      vaccination of healthcare personnel against measles. Even in countries such as
      the United States or Finland that have national policies, the recommendations are
      not uniformly implemented in healthcare facilities. Measles serosusceptibility in
      healthcare personnel varied widely across studies (median 6.5%, range 0-46%) but
      was consistently higher among younger healthcare personnel. Deficiencies in
      documentation of two doses of measles vaccination or other evidence of immunity
      among healthcare personnel presents challenges in responding to measles exposures
      in healthcare settings. Evaluating and containing exposures and outbreaks in
      healthcare settings can be disruptive and costly. Establishing policies for
      measles vaccination for healthcare personnel is an important strategy towards
      achieving measles elimination and should be a high priority for global policy
      setting groups, governments, and hospitals. 

PMID- 24280282
TI  - Selective strong synergism of Ruxolitinib and second generation tyrosine kinase
      inhibitors to overcome bone marrow stroma related drug resistance in chronic
      myelogenous leukemia.
AB  - The IC50 of TKIs is significantly increased when BCR-ABL+ K562 cell line is
      cultured in stroma conditioned media produced by BM mesenchymal cells. In
      particular, while the Imatinib IC50 in the stromal co-cultures was well above the
      in vivo through levels of the drug, the IC50s of second generation TKIs were
      still below their through levels. Moreover, we provide a formal comparison of the
      synergy between first and second generation TKIs with the JAK inhibitor
      Ruxolitinib to overcome BM stroma related TKI resistance. Taken together, our
      data provide a rationale for the therapeutic combination of TKIs and Ruxolitinib
      with the aim to eradicate primary BCR-ABL+ cells homed in BM niches. 

PMID- 24280283
TI  - High rate of uncaptured myelodysplastic syndrome cases and an improved method of
      case ascertainment.
AB  - The myelodysplastic syndromes (MDS) are often diagnosed in outpatient clinics and
      may be under-reported to state cancer registries, which predominantly rely on
      hospital records and laboratory reports. We used a new method of cancer case
      capture to determine the rate of missed cases and estimate a more accurate
      incidence of MDS. Using a unique keyword algorithm, we queried all electronic
      pathology (E-path) reports sent to the state of Florida cancer registry in 2006
      to identify potential MDS cases. A stratified, random sample of E-path reports
      was then reviewed to confirm diagnosis and assign MDS subtype. Characteristics
      were compared between captured and uncaptured MDS cases. 7111 E-path reports with
      MDS keyword hits were identified, of which only 18% linked to a registered MDS
      case, 47% linked to a different cancer, and 34% did not link with any record.
      Case review of a stratified, random sampling of 285 individuals led to the
      discovery that uncaptured cases made up 37.7% of the total true MDS cases in
      2006. It is estimated that the true incidence of MDS is 5.3 individuals out of
      100,000, compared to previous reports of 3.3 out of 100,000. Uncaptured MDS cases
      were younger and more likely to have information in the pathology report
      facilitating MDS subtype assignment. Only two-thirds of true MDS cases are
      captured in Florida using current case-finding mechanisms. Application of a
      keyword search strategy to identify cases among E-path reports is a feasible
      technique to improve MDS case ascertainment. 

PMID- 24280284
TI  - Human disease resulting from exposure to electromagnetic fields.
AB  - Electromagnetic fields (EMFs) include everything from cosmic rays through visible
      light to the electric and magnetic fields associated with electricity. While the
      high frequency fields have sufficient energy to cause cancer, the question of
      whether there are human health hazards associated with communication
      radiofrequency (RF) EMFs and those associated with use of electricity remains
      controversial. The issue is more important than ever given the rapid increase in
      the use of cell phones and other wireless devices. This review summarizes the
      evidence stating that excessive exposure to magnetic fields from power lines and
      other sources of electric current increases the risk of development of some
      cancers and neurodegenerative diseases, and that excessive exposure to RF
      radiation increases risk of cancer, male infertility, and neurobehavioral
      abnormalities. The relative impact of various sources of exposure, the great
      range of standards for EMF exposure, and the costs of doing nothing are also
      discussed.

PMID- 24280285
TI  - Neonatal phototherapy, fluids, and photorelaxation.

PMID- 24280286
TI  - Preanalytical errors: the professionals' perspective.

PMID- 24280287
TI  - The effect of centrifugation on three urine protein assays: benzethonium
      chloride, benzalkonium chloride and pyrogallol red.

PMID- 24280288
TI  - Reply: To PMID 23732774.

PMID- 24280289
TI  - Reply: To PMID 23648697.

PMID- 24280290
TI  - Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4
      activation and the Warburg effect in multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is a fatal plasma cell malignancy exhibiting
      enhanced glucose consumption associated with an aerobic glycolytic phenotype
      (i.e., the Warburg effect). We have previously demonstrated that myeloma cells
      exhibit constitutive plasma membrane (PM) localization of GLUT4, consistent with
      the dependence of MM cells on this transporter for maintenance of glucose
      consumption rates, proliferative capacity, and viability. The purpose of this
      study was to investigate the molecular basis of constitutive GLUT4 plasma
      membrane localization in MM cells. FINDINGS: We have elucidated a novel mechanism
      through which myeloma cells achieve constitutive GLUT4 activation involving
      elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant
      to promote the Warburg effect. AS160_v2-positive MM cell lines display
      constitutive Thr642 phosphorylation, known to be required for inactivation of
      AS160 Rab-GAP activity. Importantly, we show that enforced expression of AS160_v2
      is required for GLUT4 PM translocation and activation in these select MM lines.
      Furthermore, we demonstrate that ectopic expression of a full-length, phospho
      deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface
      residence, which is characteristic of MM cells. CONCLUSIONS: This is the first
      study to tie AS160 de-regulation to increased glucose consumption rates and the
      Warburg effect in cancer. Future studies investigating connections between the
      insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are
      warranted and could provide rationale for therapeutically targeting this pathway
      in MM patients with advanced disease.

PMID- 24280291
TI  - Social-ecological factors determine spatial variation in human incidence of tick
      borne ehrlichiosis.
AB  - The spatial distribution of human cases of tick-borne diseases is probably
      determined by a combination of biological and socioeconomic factors. A zoonotic
      tick-borne pathogen, Ehrlichia chaffeensis, is increasing in human incidence in
      the USA. In this study, the spatial patterns of probable and confirmed E.
      chaffeensis-associated cases of ehrlichiosis from 2000 to 2011 were investigated
      at the zip-code level in Missouri. We applied spatial statistics, including
      global and local regression models, to investigate the biological and
      socioeconomic factors associated with human incidence. Our analysis confirms that
      the distribution of ehrlichiosis in Missouri is non-random, with numerous
      clusters of high incidence. Furthermore, we identified significant, but spatially
      variable, associations between incidence and both biological and socioeconomic
      factors, including a positive association with reservoir host density and a
      negative association with human population density. Improved understanding of
      local variation in these spatial factors may facilitate targeted interventions by
      public health authorities.

PMID- 24280293
TI  - Persistent hepatitis D virus mono-infection in humanized mice is efficiently
      converted by hepatitis B virus to a productive co-infection.
AB  - BACKGROUND & AIMS: Clinical studies have shown that hepatitis delta virus (HDV)
      infection can persist for years and intrahepatic latency of the large delta
      antigen (HDAg) has been detected following liver transplantation. However, large
      HDAg arising via RNA-editing is associated with increasing amounts of non
      infectious HDV quasi-species. This study investigated whether HDV could persist
      intrahepatically in the absence of HBV in vivo and whether infectious HDV could
      subsequently be released following HBV super-infection. METHODS: Humanized mice
      were infected with HDV particles lacking HBV. To test for rescue of latent HDV
      infection 3 and 6 weeks HDV mono-infected mice were super-infected with HBV.
      Viral loads and cell toxicity were determined by qRT-PCR and
      immunohistochemistry. RESULTS: The presence of HDAg-positive human hepatocytes
      determined after 2, 3, and 6 weeks of HDV inoculation demonstrated establishment
      and maintenance of intrahepatic HDV mono-infection. Although intrahepatic amounts
      of large HDAg and edited HDV RNA forms increased over time in HDV mono-infected
      livers, HBV super-infection led to prompt viremia development (up to 10(8) HDV
      RNA and 10(7) HBV-DNA copies/ml) even after 6 weeks of latent mono-infection.
      Concurrently, the number of HDAg-positive human hepatocytes increased,
      demonstrating intrahepatic HDV spreading. The infectivity of the rescued HDV
      virions was verified by serial passage in naive chimeric mice. CONCLUSIONS: HDV
      mono-infection can persist intrahepatically for at least 6 weeks before being
      rescued by HBV. Conversion of a latent HDV infection to a productive HBV/HDV co
      infection may contribute to HDV persistence even in patients with low HBV
      replication and in the setting of liver transplantation.

PMID- 24280294
TI  - Outcome of patients with cirrhosis requiring mechanical ventilation in ICU.
AB  - INTRODUCTION: Mortality rate of patients with cirrhosis admitted to the intensive
      care unit (ICU) and requiring mechanical ventilation varies between 60 and 91%.
      The aim of our study is to assess the prognosis of these patients, their 1-year
      outcome and to analyze predictive factors of long-term mortality. METHODS: From
      May 2005 to May 2011, we studied 246 consecutive patients with cirrhosis
      requiring mechanical ventilation either at admission or during their ICU stay.
      RESULTS: Alcohol was the most common etiology of the cirrhosis (69%). Bleeding
      related to portal hypertension (30%) and severe sepsis (33%) were the most common
      reasons for admission. ICU and hospital mortality were respectively 65.9% and
      70.3%. Prognostic severity scores, the need for other organ support therapy,
      infection, and total bilirubin value at ICU admission were significantly
      associated with ICU mortality. Eighty-four patients (34.1%) were discharged from
      the ICU. Among these patients, the one-year survival was only of 32%. Logistic
      regression analysis, using survival at one year as the endpoint, identified two
      independent risk factors: the length of ventilation (odds ratio [OR] = 1.1; 95%
      CI, 1.0-1.2; p = 0.02) and total bilirubin at ICU discharge (OR = 1.3; 95% CI,
      1.1-1.5; p = 0.006). CONCLUSION: Patients with cirrhosis admitted to the liver
      ICU and who required mechanical ventilation have a poor prognosis with a 1-year
      mortality of 89%. At ICU discharge, a total bilirubin level higher than 64.5
      MUmol/L and length of ventilation higher than 9 days could help the hepatologists
      to identify patients at risk of death in the year following the ICU discharge.

PMID- 24280292
TI  - Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity
      in the liver transplant setting.
AB  - Studies of boceprevir and telaprevir based antiviral therapy in liver transplant
      (LT) recipients with hepatitis C genotype 1 infection have demonstrated dramatic
      increases in tacrolimus, cyclosporine, and mTOR inhibitor exposure. In addition
      to empiric dose reductions, daily monitoring of immunosuppressant blood levels is
      required when initiating as well as discontinuing the protease inhibitors to
      maximize patient safety. Although improved suppression of HCV replication is
      anticipated, 20 to 40% of treated subjects have required early treatment
      discontinuation due to various adverse events including anemia (100%), infection
      (30%), nephrotoxicity (20%) and rejection (5 to 10%). Simeprevir and faldaprevir
      will likely have improved efficacy and safety profiles but potential drug
      interactions with other OATP1B1 substrates and unconjugated hyperbilirubinemia
      are expected. In contrast, sofosbuvir and daclatasvir based antiviral therapy are
      not expected to lead to clinically significant drug-drug interactions in LT
      recipients but confirmatory studies are needed. Liver transplant recipients may
      also be at increased risk of developing drug induced liver injury (DILI).
      Establishing a diagnosis of DILI in the transplant setting is very difficult with
      the variable latency, laboratory features and histopathological manifestations of
      hepatotoxicity associated with a given drug, the need to exclude competing causes
      of allograft injury, and the lack of an objective and verifiable confirmatory
      test. Nonetheless, a heightened awareness of the possibility of DILI is warranted
      in light of the large number of medications used in LT recipients and the
      potential adverse impact that DILI may have on patient outcomes. 

PMID- 24280296
TI  - Cerebellar granule neuron progenitors are the source of Hk2 in the postnatal
      cerebellum.

PMID- 24280295
TI  - A rare case of urinary schistosomiasis in Turkey.
AB  - Schistosomiasis is a chronic, parasitic disease and is endemic in some countries,
      primarily in Africa, Latin America and Asia. In some regions, Schistosoma
      haematobium is one of the principal causes of haematuria. In Turkey, due to the
      increasing amount of travel to and from endemic regions, the number of cases is
      also rising. We report a case of a 22-year-old Nigerian male who was admitted to
      our hospital with haematuria. Direct microbiological examination revealed S.
      haematobium eggs in his urine specimen. Schistosomiasis was diagnosed by
      pathology testing. Schistosomiasis has not been seen frequently in Turkey, and we
      therefore discuss the epidemiology, treatment options and clinical importance of
      S. haematobium. 

PMID- 24280297
TI  - Bile acid-controlled transgene expression in mammalian cells and mice.
AB  - In recent years, using trigger-inducible mammalian gene switches to design
      sophisticated transcription-control networks has become standard practice in
      synthetic biology. These switches provide unprecedented precision, complexity and
      reliability when programming novel mammalian cell functions. Metabolite
      responsive repressors of human-pathogenic bacteria are particularly attractive
      for use in these orthogonal synthetic mammalian gene switches because the trigger
      compound sensitivity often matches the human physiological range. We have
      designed both a bile acid-repressible (BEAROFF) as well as a bile-acid-inducible
      (BEARON) gene switch by capitalizing on components that have evolved to manage
      bile acid resistance in Campylobacter jejuni, the leading causative agent of
      human food-borne enteritis. We have shown that both of these switches enable bile
      acid-adjustable transgene expression in different mammalian cell lines as well as
      in mice. For the BEAROFF device, the C. jejuni repressor CmeR was fused to the
      VP16 transactivation domain to create a synthetic transactivator that activates
      minimal promoters containing tandem operator modules (Ocme) in a bile acid
      repressible manner. Fusion of CmeR to a transsilencing domain resulted in an
      artificial transsilencer that binds and represses a constitutive Ocme-containing
      promoter until it is released by addition of bile acid (BEARON). A tailored multi
      step tuning program for the inducible gene switch, which included the
      optimization of individual component performance, control of their relative
      abundances, the choice of the cell line and trigger compound, resulted in a
      BEARON device with significantly improved bile acid-responsive control
      characteristics. Synthetic metabolite-triggered gene switches that are able to
      interface with host metabolism may foster advances in future gene and cell-based
      therapies. 

PMID- 24280298
TI  - Unusual solvatochromic absorbance probe behaviour within mixtures of
      poly(ethylene glycol)-400+ionic liquid, [bmim][Tf2N].
AB  - The potentially green solvents made up of ionic liquids (ILs) and poly(ethylene
      glycols) may have wide range of the applications in many chemical and biochemical
      fields. In the present work, solvatochromic absorbance probe behaviour is used to
      assess the physicochemical properties of the mixtures composed of PEG-400+IL, 1
      butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [bmim][Tf2N]. Lowest
      energy intramolecular charge-transfer absorbance maxima of a betaine dye, i.e.,
      E(T)(N), indicates the dipolarity/polarizability and/or hydrogen-bond donating
      (HBD) acidity of the [bmim][Tf2N]+PEG-400 mixtures to be even higher than that of
      neat [bmim][Tf2N], the solution component with higher dipolarity/polarizability
      and/or HBD acidity. Dipolarity/polarizability (pi(*)) obtained separately from
      the electronic absorbance response of probe N,N-diethyl-4-nitroaniline, and the
      HBD acidity (alpha) of PEG-400+[bmim][Tf2N] mixtures are also observed to be
      anomalously high. A comparative study of the PEG+IL mixtures has also been done
      with PEG-400+molecular organic solvents (protic polar [methanol], aprotic polar
      [N,N-dimethylformamide], and non polar, [benzene]) mixtures, but these mixtures
      do not show this type of unusual behaviour. A four-parameter simplified combined
      nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation is shown to
      satisfactorily predict the solvatochromic parameters within PEG-400+different
      solvent mixtures.

PMID- 24280299
TI  - Crystal structure, spectroscopic characterization and density functional studies
      of (E)-1-((3-methoxyphenylimino)methyl)naphthalen-2-ol.
AB  - The Schiff base compound (E)-1-((3-methoxyphenylimino)methyl)naphthalen-2-ol was
      synthesized from the reaction of 2-hydroxy-1-naphthaldehyde with 3
      methoxyaniline. The structural properties of the compound has been characterized
      by using FT-IR, UV-vis and X-ray single-crystal methods. According to X-ray
      diffraction result, the title compound exists in the phenol-imine tautomeric
      form. The molecular geometry, vibrational frequencies of the compound in the
      ground state have been calculated using the density functional theory (DFT/B3LYP)
      method with the 6-311++G(d,p) basis set, and compared with the experimental data.
      The obtained results show that the optimized molecular geometry is well reproduce
      the crystal structure. The theoretical vibrational frequencies are in good
      agreement with the experimental values. The calculations of electronic absorption
      spectra of tautomeric forms of the compound were performed by using TD-DFT
      calculations both in the gas phase and ethanol solvent. To investigate the
      tautomeric stability, optimization calculations at the B3LYP/6-311++G(d,p) level
      were performed for the phenol-imine and keto-amine forms of the compound.
      According to calculated results, the OH form is more stable than NH form. In
      addition, molecular electrostatic potential (MEP), frontier molecular orbital
      analysis (HOMO-LUMO), thermodynamic and, non-linear optical (NLO) properties of
      the compound were investigated using same theoretical calculations. 

PMID- 24280300
TI  - Investigation of biological cell-protein interactions using SPR sensor through
      laser scanning confocal imaging-surface plasmon resonance system.
AB  - A new method for investigating biological cell-protein interactions was developed
      by using a laser scanning confocal imaging-surface plasmon resonance (LSCI-SPR)
      system. Mouse normal IgG was modified on the SPR chip. The suspension mouse
      lymphocyte cancer cells (L5178Y cells) labeled by Hoechst33342 freely flowed into
      the surface of the SPR sensor chip. By changing the concentration of the cells,
      the fluorescence images and the SPR signal were synchronously recorded in real
      time. The red fluorescence points in the imaging region increased with increase
      in the concentration of the mouse lymphocyte cancer cells and fit well with the
      change in the SPR signal. Different suspending cells were chosen to investigate
      cell-protein interactions through antigen-antibody reactions on the biological
      cell surfaces through binding detection. This method has potential application in
      cell biology and pharmacology. 

PMID- 24280301
TI  - Study on the adsorption of DNA on the layered double hydroxides (LDHs).
AB  - Four kinds of layered double hydroxides (LDHs) were prepared by chemical
      coprecipitation method and used as DNA adsorbents. Multiple characterization
      tools such as power X-ray diffraction (XRD), Fourier transform infrared (FTIR)
      spectroscopy and Standard electronic modules (SEM) were employed to characterize
      the LDHs. By examining the effect of initial concentration, solution pH,
      adsorption experiments were carried out to investigate the adsorption capacities
      of LDHs for DNA. The results revealed that the LDHs with Mg/Al=3 had higher
      ability on adsorbing the DNA and were not affected by pH values. The LDHs
      exhibited excellent adsorption properties and completely adsorbed DNA within 2h.
      The adsorption equilibrium data were fitted to the Langmuir and Freundlich
      models, showing that the Langmuir model which represented monolayer adsorption
      had better correlation with the adsorption linear equation. In addition, Circular
      dichroism (CD) spectrum, UV-vis spectorscopy and agarose gel electrophoresis
      revealed the integrity of DNA structure, suggesting that there had no damage on
      the DNA structure during the adsorption process. 

PMID- 24280302
TI  - Spectroscopic studies (FTIR, FT-Raman and UV-Visible), normal coordinate
      analysis, NBO analysis, first order hyper polarizability, HOMO and LUMO analysis
      of (1R)-N-(Prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine molecule by ab initio HF
      and density functional methods.
AB  - The Fourier transform infrared (FT-IR) and FT-Raman of (1R)-N-(Prop-2-yn-1-yl)
      2,3-dihydro-1H-inden-1-amine (1RNPDA) were recorded in the regions 4000-400 cm(
      1) and 4000-100 cm(-1) respectively. A complete assignment and analysis of the
      fundamental vibrational modes of the molecule were carried out. The observed
      fundamental modes have been compared with the harmonic vibrational frequencies
      computed using HF method by employing 6-31G(d,p) basis set and DFT(B3LYP) method
      by employing 6-31G(d,p) basis set. The vibrational studies were interpreted in
      terms of Potential Energy Distribution (PED). The complete vibrational frequency
      assignments were made by Normal Co-ordinate Analysis (NCA) following the scaled
      quantum mechanical force field methodology (SQMFF). The first order hyper
      polarizability (beta0) of this molecular system and related properties (alpha,
      MU, and Deltaalpha) are calculated using B3LYP/6-31G(d,p) method based on the
      finite-field approach. The thermodynamic functions of the title compound were
      also performed at the above methods and basis set. A detailed interpretation of
      the infrared and Raman spectra of 1RNPDA is reported. The (1)H and (13)C nuclear
      magnetic resonance (NMR) chemical shifts of the molecule were calculated using
      the GIAO method confirms with the experimental values. Stability of the molecule
      arising from hyper-conjugative interactions and charge delocalization has been
      analyzed using Natural Bond Orbital (NBO) analysis. UV-vis spectrum of the
      compound was recorded and electronic properties such as excitation energies,
      oscillator strength and wavelength were performed by TD-DFT/B3LYP using 6
      31G(d,p) basis set. The HOMO and LUMO energy gap reveals that the energy gap
      reflects the chemical activity of the molecule. The observed and calculated wave
      numbers are formed to be in good agreement. The experimental spectra also
      coincide satisfactorily with those of theoretically constructed spectra.

PMID- 24280303
TI  - Understanding the link between early sexual initiation and later sexually
      transmitted infection: test and replication in two longitudinal studies.
AB  - PURPOSE: Age at sexual initiation is strongly associated with sexually
      transmitted infections (STI); yet, prevention programs aiming to delay sexual
      initiation have shown mixed results in reducing STI. This study tested three
      explanatory mechanisms for the relationship between early sexual debut and STI:
      number of sexual partners, individual characteristics, and environmental
      antecedents. METHODS: A test-and-replicate strategy was employed using two
      longitudinal studies: the Seattle Social Development Project (SSDP) and Raising
      Healthy Children (RHC). Childhood measures included pubertal age, behavioral
      disinhibition, and family, school, and peer influences. Alcohol use and age of
      sexual debut were measured during adolescence. Lifetime number of sexual partners
      and having sex under the influence were measured during young adulthood. Sexually
      transmitted infection diagnosis was self-reported at age 24. Early sex was
      defined as debut at <15 years. Path models were developed in SSDP evaluating
      relationships between measures, and were then tested in RHC. RESULTS: The
      relationship between early sex and STI was fully mediated by lifetime sex
      partners in SSDP, but only partially in RHC, after accounting for co-occurring
      factors. Behavioral disinhibition predicted early sex, early alcohol use, number
      of sexual partners, and sex under the influence, but had no direct effect on STI.
      Family management protected against early sex and early alcohol use, whereas
      antisocial peers exacerbated the risk. CONCLUSIONS: Early sexual initiation, a
      key mediator of STI, is driven by antecedents that influence multiple risk
      behaviors. Targeting co-occurring individual and environmental factors may be
      more effective than discouraging early sexual debut and may concomitantly improve
      other risk behaviors.

PMID- 24280304
TI  - Lagging behind or not? Four distinctive social participation patterns among young
      adults with chronic conditions.
AB  - PURPOSE: Typical childhood and adolescent development and acquiring self
      management skills are crucial for a satisfying adult life and autonomy in social
      participation. The aims of this study were to identify patterns of autonomy in
      social participation and to explore differences between these patterns. METHODS:
      Adolescents with various chronic conditions participating in a survey in 2006
      (T0) were re-invited for a follow-up study (T1) in 2012. The young adults (18-25
      years of age) assessed self-management skills, their condition's impact on school
      or work, health-related quality of life (HRQoL), and social participation in
      various domains. Patterns were identified through cluster analysis. Differences
      between patterns were analyzed in bivariate and multivariate analyses. RESULTS:
      Compared with healthy age-mates, our sample (n = 483) generally lagged behind in
      social participation. Four patterns emerged: typical developers, financially
      secure laggers, slow developers, and outgoing laggers. The patterns differed
      regarding gender, educational level, attending special education, having
      disability benefits, and degree of physical limitations. Groups with a higher
      level of autonomy in social participation did not necessarily have higher HRQoL
      but did report higher self-efficacy and independence at both measurements.
      CONCLUSIONS: Autonomy in some participation domains can coincide with a lack of
      autonomy in others. In addition, better social participation does not necessarily
      correlate with higher HRQoL, or vice versa. Yet, more social participation was
      associated with more self-efficacy and independence. Our results emphasize that
      there is no standardized approach. Clinicians should take care to address all
      life areas in clinical practice to screen patients' lived experiences and the
      need for social and self-management support.

PMID- 24280305
TI  - The N-terminal domain of DnaT, a primosomal DNA replication protein, is crucial
      for PriB binding and self-trimerization.
AB  - DnaT and PriB are replication restart primosomal proteins required for re
      initiating chromosomal DNA replication in bacteria. Although the interaction of
      DnaT with PriB has been proposed, which region of DnaT is involved in PriB
      binding and self-trimerization remains unknown. In this study, we identified the
      N-terminal domain in DnaT (aa 1-83) that is important in PriB binding and self
      trimerization but not in single-stranded DNA (ssDNA) binding. DnaT and the
      deletion mutant DnaT42-179 protein can bind to PriB according to native
      polyacrylamide gel electrophoresis, Western blot analysis, and pull-down assay,
      whereas DnaT84-179 cannot bind to PriB. In contrast to DnaT, DnaT26-179, and
      DnaT42-179 proteins, which form distinct complexes with ssDNA of different
      lengths, DnaT84-179 forms only a single complex with ssDNA. Analysis of DnaT84
      179 protein by gel filtration chromatography showed a stable monomer in solution
      rather than a trimer, such as DnaT, DnaT26-179, and DnaT42-179 proteins. These
      results constitute a pioneering study of the domain definition of DnaT. Further
      research can directly focus on determining how DnaT binds to the PriA-PriB-DNA
      tricomplex in replication restart by the hand-off mechanism. 

PMID- 24280307
TI  - The ligamentum teres test: a novel and effective test in diagnosing tears of the
      ligamentum teres.
AB  - BACKGROUND: A ligamentum teres (LT) injury is a common finding at the time of hip
      arthroscopic surgery in patients with chronic groin and hip pain; however, LT
      tears have been difficult to identify before surgery. There have been no unique
      features identified on history assessment, physical examination, or imaging that
      reliably identify injuries of the LT preoperatively. PURPOSE: To report a new
      clinical examination to assess the presence of an LT tear: the LT test. STUDY
      DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The study
      consisted of 75 patients undergoing hip arthroscopic surgery for multiple
      lesions. Each patient was evaluated by 2 independent examiners using the LT test,
      leading to a total of 150 tests being performed. The LT test is conducted with
      the hip flexed at 70 degrees  and 30 degrees  short of full abduction; the hip is
      then internally and externally rotated to its limits of motion. Pain on either
      internal or external rotation is consistent with a positive LT test result. Hip
      arthroscopic surgery was then performed and all intra-articular abnormalities
      noted. Arthroscopic images were taken of each LT and examined by a third
      independent examiner who determined the presence or absence of a tear. Clinical
      examination findings were compared with the arthroscopic findings to determine
      the sensitivity, specificity, and positive and negative predictive values. In
      addition, the presence of intra-articular pathological lesions was compared with
      the test results to determine if there was a correlation between the presence of
      an intra-articular pathological abnormality and a positive LT test result.
      RESULTS: Of the 150 examinations performed, the test result was positive 55% of
      the time (77 examinations). The sensitivity and specificity of the test were 90%
      and 85%, respectively. The positive predictive value was 84%, and the negative
      predictive value was 91%. The presence of an LT tear, pincer lesion, and labral
      tear that required repair was associated with a positive LT test result. The
      kappa coefficient for interobserver reliability was .80. CONCLUSION: The LT test
      is an effective way of assessing the presence of LT tears with moderate to high
      interobserver reliability. In addition to an LT tear, the presence of a pincer
      lesion or labral tear requiring repair are also associated with a positive LT
      test result.

PMID- 24280306
TI  - Ovarian cancer stem-like cells show induced translineage-differentiation capacity
      and are suppressed by alkaline phosphatase inhibitor.
AB  - Spheroid formation is one property of stem cells-such as embryo-derived or neural
      stem cells-that has been used for the enrichment of cancer stem-like cells
      (CSLCs). However, it is unclear whether CSLC-derived spheroids are heterogeneous
      or whether they share common embryonic stemness properties. Understanding these
      features might lead to novel therapeutic approaches. Ovarian carcinoma is a
      deadly disease of women. We identified two types of spheroids (SR1 and SR2) from
      ovarian cancer cell lines and patients' specimens according to their morphology.
      Both types expressed stemness markers and could self-renew and initiate tumors
      when a low number of cells were used. Only SR1 could differentiate into multiple
      lineage cell types under specific induction conditions. SR1 spheroids could
      differentiate to SR2 spheroids through epithelial-mesenchymal transition.
      Alkaline phosphatase (ALP) was highly expressed in SR1 spheroids, decreased in
      SR2 spheroids, and was absent in differentiated progenies in accordance with the
      loss of stemness properties. We verified that ALP can be a marker for ovarian
      CSLCs, and patients with greater ALP expression is related to advanced clinical
      stages and have a higher risk of recurrence and lower survival rate. The ALP
      inhibitor, levamisole, disrupted the self-renewal of ovarian CSLCs in vitro and
      tumor growth in vivo. In summary, this research provides a plastic ovarian cancer
      stem cell model and a new understanding of the cross-link between stem cells and
      cancers.This results show that ovarian CSLCs can be suppressed by levamisole. Our
      findings demonstrated that some ovarian CSLCs may restore ALP activity, and this
      suggests that inhibition of ALP activity may present a new opportunity for
      treatment of ovarian cancer.

PMID- 24280308
TI  - Anterior talofibular ligament ruptures, part 2: biomechanical comparison of
      anterior talofibular ligament reconstruction using semitendinosus allografts with
      the intact ligament.
AB  - BACKGROUND: Anatomic reconstructions of the lateral ankle ligaments with grafts
      have been proposed for patients with generalized ligamentous laxity, long
      standing instability with attenuated native tissues, varus hindfoot misalignment,
      or failed prior lateral ligament surgery and for very large patients or elite
      athletes because of increased demands. HYPOTHESIS: Anatomic reconstruction of the
      anterior talofibular ligament (ATFL) using a semitendinosus allograft fixed with
      biocomposite interference fit screws would have similar biomechanical properties
      to the intact ATFL at time zero in a cadaveric model. STUDY DESIGN: Controlled
      laboratory study. METHODS: Allograft reconstruction of the ATFL was performed in
      6 fresh-frozen cadaveric ankles. The specimens were loaded to failure to
      determine the strength and stiffness of the reconstruction and compared with data
      from 6 cadaveric specimens with intact ATFLs. RESULTS: The mean ultimate load to
      failure of the allograft reconstruction (170.7 +/- 54.8 N) was not significantly
      different from that of the intact ATFL (154.0 +/- 63.7 N). The mean stiffness of
      the allograft reconstruction (23.1 +/- 9.3 N/mm) was also not significantly
      different from that of the intact ATFL (14.5 +/- 4.4 N/mm). CONCLUSION: Anatomic
      reconstruction of the ATFL with allografts demonstrated similar strength and
      stiffness to the native ligament at time zero in a fresh-frozen cadaveric model.
      CLINICAL RELEVANCE: This technique of anatomic reconstruction of the ATFL with
      allografts has biomechanical validation for use in clinical situations where a
      Brostrom repair of the lateral ankle ligaments is unlikely to be successful or
      has previously failed.

PMID- 24280309
TI  - The knockdown of OsVIT2 and MIT affects iron localization in rice seed.
AB  - BACKGROUND: The mechanism of iron (Fe) uptake in plants has been extensively
      characterized, but little is known about how Fe transport to different
      subcellular compartments affects Fe localization in rice seed. Here, we discuss
      the characterization of a rice vacuolar Fe transporter 2 (OsVIT2) T-DNA insertion
      line (osvit2) and report that the knockdown of OsVIT2 and mitochondrial Fe
      transporter (MIT) expression affects seed Fe localization. FINDINGS: osvit2
      plants accumulated less Fe in their shoots when grown under normal or excess Fe
      conditions, while the accumulation of Fe was comparable to that in wild-type (WT)
      plants under Fe-deficient conditions. The accumulation of zinc, copper, and
      manganese also changed significantly in the shoots of osvit2 plants. The growth
      of osvit2 plants was also slow compared to that of WT plants. The concentration
      of Fe increased in osvit2 polished seeds. Previously, we reported that the
      expression of OsVIT2 was higher in MIT knockdown (mit-2) plants, and in this
      study, the accumulation of Fe in mit-2 seeds decreased significantly.
      CONCLUSIONS: These results suggest that vacuolar Fe trafficking is important for
      plant Fe homeostasis and distribution, especially in plants grown in the presence
      of excess Fe. Moreover, changes in the expression of OsVIT2 and MIT affect the
      concentration and localization of metals in brown rice as well as in polished
      rice seeds.

PMID- 24280310
TI  - Balance between beneficial microflora and Staphylococcus aureus colonisation: in
      vivo evaluation in patients with atopic dermatitis during hydrotherapy.
AB  - BACKGROUND: The role of the balance between Staphylococcus aureus and commensal
      flora in the severity of atopic dermatitis (AD) lesions is not well understood.
      OBJECTIVES: To determine the structure of skin microbiome in patients with AD and
      its changes during an 18-day course of hydrotherapy and to assess the association
      between S. aureus and micro-organism colonisation, local skin condition and AD
      severity. METHODS: Three skin areas (xerotic, inflammatory and healthy) were
      identified in 25 moderate to severe AD patients for sampling before treatment,
      just after (day 1), and at day 10 and day 18. The structure of the bacterial
      community in the samples was assessed using a molecular biology approach based on
      16S rRNA gene profiling. At each visit, AD severity was measured globally by the
      SCORAD index and at the lesional and healthy sampling sites. RESULTS: Clustering
      analysis of 296 samples showed two different bacterial community profiles: one
      with 2 peaks corresponding to S. aureus, the other displayed multiple peaks,
      identified as diversified microflora. At baseline, xerotic areas seemed to be
      less colonised by S. aureus than inflammatory areas. After 18 days of
      hydrotherapy, the number of lesional sites colonised by S. aureus (p<0.05) and
      the SCORAD index (p<0.00001) were significantly reduced, mainly in inflammatory
      and moist areas, promoting the emergence of a diversified microflora.
      CONCLUSIONS: We identified two bacterial community profiles corresponding to S.
      aureus and diversified microflora. The competitive balance between both profiles
      appears to be a key element associated with the severity of AD lesions.

PMID- 24280311
TI  - Prognostic difference between paroxysmal and non-paroxysmal atrial fibrillation
      in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: The association of atrial fibrillation (AF) with sudden death and the
      difference in prognostic significance between paroxysmal and non-paroxysmal AF
      remains unclear in patients with hypertrophic cardiomyopathy (HCM). Our aim was
      to investigate the clinical significance of AF, and to assess the prognostic
      difference between paroxysmal and non-paroxysmal AF in HCM patients. METHODS: The
      study included 430 HCM patients. Documentation of AF was based on
      electrocardiograms obtained either after the acute onset of symptoms or
      fortuitously during routine examination of asymptomatic patients. RESULTS: AF was
      detected in 120 patients (27.9%). In the patients with AF, syncope and non
      sustained ventricular tachycardia were more frequent and the left atrial
      dimension was larger. Multivariate analysis showed that AF was an independent
      determinant of the outcome, including the risk of HCM-related death (adjusted
      hazard ratio 3.57, p<0.001) and sudden death (adjusted hazard ratio 2.61,
      p=0.038). When patients with AF were divided into subgroups with paroxysmal AF
      (n=75) or non-paroxysmal AF (n=45), only paroxysmal AF was identified as an
      independent determinant of the outcome, including the risk of HCM-related death
      (adjusted hazard ratio 5.24, p<0.001) and sudden death (adjusted hazard ratio
      4.67, p=0.002). CONCLUSIONS: AF is a common supraventricular arrhythmia in HCM
      and has an adverse influence on the prognosis. In addition, each type of AF had a
      different clinical impact, with paroxysmal AF being a significant independent
      determinant of an adverse outcome, including sudden death.

PMID- 24280313
TI  - Rumors of the death of consumer genomics are greatly exaggerated.

PMID- 24280312
TI  - WikiPathways for plants: a community pathway curation portal and a case study in
      rice and arabidopsis seed development networks.
AB  - BACKGROUND: Next-generation sequencing and 'omics' platforms are used extensively
      in plant biology research to unravel new genomes and study their interactions
      with abiotic and biotic agents in the growth environment. Despite the
      availability of a large and growing number of genomic data sets, there are only
      limited resources providing highly-curated and up-to-date metabolic and
      regulatory networks for plant pathways. RESULTS: Using PathVisio, a pathway
      editor tool associated with WikiPathways, we created a gene interaction network
      of 430 rice (Oryza sativa) genes involved in the seed development process by
      curating interactions reported in the published literature. We then applied an
      InParanoid-based homology search to these genes and used the resulting gene
      clusters to identify 351 Arabidopsis thaliana genes. Using this list of
      homologous genes, we constructed a seed development network in Arabidopsis by
      processing the gene list and the rice network through a Perl utility software
      called Pathway GeneSWAPPER developed by us. In order to demonstrate the utility
      of these networks in generating testable hypotheses and preliminary analysis
      prior to more in-depth downstream analysis, we used the expression viewer and
      statistical analysis features of PathVisio to analyze publicly-available and
      published microarray gene expression data sets on diurnal photoperiod response
      and the seed development time course to discover patterns of coexpressed genes
      found in the rice and Arabidopsis seed development networks. These seed
      development networks described herein, along with other plant pathways and
      networks, are freely available on the plant pathways portal at WikiPathways
      (http://plants.wikipathways.org). CONCLUSION: In collaboration with the
      WikiPathways project we present a community curation and analysis platform for
      plant biologists where registered users can freely create, edit, share and
      monitor pathways supported by published literature. We describe the curation and
      annotation of a seed development network in rice, and the projection of a
      similar, gene homology-based network in Arabidopsis. We also demonstrate the
      utility of the Pathway GeneSWAPPER (PGS) application in saving valuable time and
      labor when a reference network in one species compiled in GPML format is used to
      project a similar network in another species based on gene homology.

PMID- 24280314
TI  - Life history and emergence pattern of Cloeon dipterum (Ephemeroptera: Baetidae)
      in Korea.
AB  - Cloeon dipterum (L.) (Ephemeroptera: Baetidae), the common wetland mayfly,
      emerges and oviposits every season, except winter, and has overlapping
      generations in the temperate region. We investigated the life history of C.
      dipterum associated with drought. Field experiments and sampling were conducted
      in a wetland (25 by 80 m) located in central Korea. Larvae were sampled weekly
      within two habitat types (a large, deep wetland and a small, shallow wetland)
      using a dredge sampler, and adults were sampled every 2 d with cube emergence
      traps, from July 2011 to September 2012 (except winter). C. dipterum had an
      extended emergence period from late April to early October with four peaks: early
      May, mid-June, July, and August/September. When the water depth was shallow
      because of drought, emergence was suppressed and delayed. The accumulated degree
      days and body length of the overwintering cohort that emerged in spring 2012 were
      markedly larger and longer than those of other cohorts. Adults emerged
      intensively around sunset. C. dipterum has a multivoltine life cycle with four
      cohorts per year; its life history and population density can be changed by
      natural disturbances such as drought and fish predation. 

PMID- 24280315
TI  - Beyond allostatic load: rethinking the role of stress in regulating human
      development.
AB  - How do exposures to stress affect biobehavioral development and, through it,
      psychiatric and biomedical disorder? In the health sciences, the allostatic load
      model provides a widely accepted answer to this question: stress responses, while
      essential for survival, have negative long-term effects that promote illness.
      Thus, the benefits of mounting repeated biological responses to threat are traded
      off against costs to mental and physical health. The adaptive calibration model,
      an evolutionary-developmental theory of stress-health relations, extends this
      logic by conceptualizing these trade-offs as decision nodes in allocation of
      resources. Each decision node influences the next in a chain of resource
      allocations that become instantiated in the regulatory parameters of stress
      response systems. Over development, these parameters filter and embed information
      about key dimensions of environmental stress and support, mediating the
      organism's openness to environmental inputs, and function to regulate life
      history strategies to match those dimensions. Drawing on the adaptive calibration
      model, we propose that consideration of biological fitness trade-offs, as
      delineated by life history theory, is needed to more fully explain the complex
      relations between developmental exposures to stress, stress responsivity,
      behavioral strategies, and health. We conclude that the adaptive calibration
      model and allostatic load model are only partially complementary and, in some
      cases, support different approaches to intervention. In the long run, the field
      may be better served by a model informed by life history theory that addresses
      the adaptive role of stress response systems in regulating alternative
      developmental pathways. 

PMID- 24280316
TI  - Mental health law and the UN Convention on the rights of Persons with
      Disabilities.
AB  - People with a mental illness may be subject to the UN Convention on the Rights of
      Persons with Disabilities (CRPD), depending on definitions of terms such as
      'impairment', 'long-term' and the capaciousness of the word 'includes' in the
      Convention's characterisation of persons with disabilities. Particularly
      challenging under the CRPD is the scope, if any, for involuntary treatment.
      Conventional mental health legislation, such as the Mental Health Act (England
      and Wales) appears to violate, for example, Article 4 ('no discrimination of any
      kind on the basis of disability'), Article 12 (persons shall 'enjoy legal
      capacity on an equal basis with others in all aspects of life') and Article 14
      ('the existence of a disability shall in no case justify a deprivation of
      liberty'). We argue that a form of mental health law, such as the Fusion Law
      proposal, is consistent with the principles of the CRPD. Such law is aimed at
      eliminating discrimination against persons with a mental illness. It covers all
      persons regardless of whether they have a 'mental' or a 'physical' illness, and
      only allows involuntary treatment when a person's decision-making capability
      (DMC) for a specific treatment decision is impaired - whatever the health setting
      or cause of the impairment - and where supported decision making has failed. In
      addition to impaired DMC, involuntary treatment would require an assessment that
      such treatment gives the person's values and perspective paramount importance. 

PMID- 24280317
TI  - Sample size calculation.
AB  - When designing any research project, definition is required of the sample size
      needed in order to carry out the study. This sample size is an estimate of the
      number of patients required in accordance with the pursued study objective. In
      this context, it is more efficient in terms of both cost and time to use samples
      than to work with the entire population. The present article describes the way to
      establish sample size in the kinds of studies most frequently found in health
      research, and how to calculate it using the epicalc package included in the
      shareware R program. A description is provided of the formulae used to calculate
      sample sizes for the estimation of a mean and percentage (referring to both
      finite and infinite populations) and for the comparison of two proportions and
      two means. Likewise, examples of the application of the mentioned statistical
      package are provided. 

PMID- 24280318
TI  - The association of sedentary lifestyle with childhood asthma. The role of nurse
      as educator.
AB  - BACKGROUND: To provide a summary of the existing published knowledge on the
      association between sedentary lifestyle and childhood asthma. Twelve years ago,
      the first longitudinal studies carried out in children showed a relationship
      between physical activity and asthma. Several epidemiological studies confirmed
      these findings, with sedentary lifestyle predicting the onset of asthma. METHODS:
      A systematic review of epidemiological studies was conducted within the MEDLINE
      database. Epidemiological studies on children subjects, published in English were
      included in the review. A comprehensive literature search yielded 50 studies for
      further consideration. Following the application of the eligibility criteria, we
      identified 11 studies. RESULTS: A positive association and an excess risk of
      asthma during childhood were revealed to sedentary lifestyle. The findings proved
      the association between childhood asthma and sedentary lifestyle. The correlation
      between bronchial asthma and sedentary life during childhood and identifying
      whether preventable or treatable risk factors exist needs to be determined.
      Further research on the topic is essential for safer and standardised
      conclusions. CONCLUSIONS AND PRACTICE IMPLICATION: Asthma can be controlled when
      managed properly. The role of the nurse as an educator should establish and
      maintain a relationship with patients in order to help them manage their disease.
      The steps towards asthma management will help paediatric patients to guide their
      approach to the condition.

PMID- 24280320
TI  - The healthy babies curriculum.

PMID- 24280322
TI  - Editors' message.

PMID- 24280321
TI  - Molecular characteristics of Staphylococcus aureus isolated from a major hospital
      in Lebanon.
AB  - OBJECTIVES: The occurrence and dissemination of methicillin-resistant
      Staphylococcus aureus (MRSA) in healthcare settings and the community and its
      risk of being introduced into hospitals are matters of great concern. The purpose
      of this study was to conduct a miniaturized epidemiological analysis of S. aureus
      associated infections and to characterize the isolates by a variety of molecular
      typing techniques. Ongoing molecular surveillance is essential to prevent S.
      aureus strains from becoming endemic in the Lebanese healthcare setting. METHODS:
      A total of 132 S. aureus from different clinical specimens were isolated over a 6
      month period. Characterization of the isolates was done by detection of the mecA
      gene, Panton-Valentine leukocidin determinant detection, staphylococcal
      chromosomal cassette (SCCmec) typing of MRSA, S. aureus protein A (spa) typing,
      multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and
      antibiogram analysis. RESULTS: MRSA represented 30% of the isolates, with PVL
      being detected in 54% of MRSA and 12% of methicillin-susceptible S. aureus
      (MSSA). A difference between MRSA and MSSA was observed in the spa types.
      Clustering SCCmec with MLST identified seven MRSA and 20 MSSA clones, with PVL
      positive ST80-MRSA-IV being the dominant clone (7%), while PFGE revealed 32
      groups with 80% cutoff similarity. CONCLUSIONS: Although the results of this
      study are based on samples collected from one hospital, the high diversity
      observed along with the lack of any equivalence in the genetic backgrounds of the
      major MSSA and MRSA clones, emphasizes the urgent need for standardized
      surveillance combined with the application of well-validated typing methods to
      assess the occurrence of MRSA and subsequently to control its spread.

PMID- 24280323
TI  - Invited commentary.

PMID- 24280324
TI  - Aspirin responsiveness safely lowers perioperative cardiovascular risk.
AB  - INTRODUCTION: Vascular surgeries are related to high cardiac morbidity and
      mortality, and the maintenance of aspirin in the perioperative period has a
      protective effect. The purpose of this study was to evaluate the association
      between preoperative platelet aggregability and perioperative cardiovascular (CV)
      events. METHODS: A preoperative platelet aggregation test was performed on an
      impedance aggregometer in response to collagen and to arachidonic acid (AA) for
      191 vascular surgery patients under chronic use of aspirin. We analyzed the
      following CV events: acute myocardial infarction, unstable angina, isolated
      troponin elevation, acute ischemic stroke, reoperation, and cardiac death.
      Hemorrhagic events were also evaluated and classified according to the
      Thrombolysis In Myocardial Infarction criteria. RESULTS: The incidence of CV
      events was 22% (n = 42). Higher platelet response to AA was associated with CV
      events, so that patients in the fourth quartile (higher than 11Omega) had almost
      twice the incidence of CV events when compared with the three lower quartiles:
      35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic
      instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval
      [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014),
      preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet
      aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034).
      Platelet aggregability was not associated with hemorrhagic events, even when we
      compared the lowest quartile of AA platelet aggregability (0-1.00 Omega) with the
      three upper quartiles (>1.00 Omega; OR, 0.77; 95% CI, 0.43-1.37; P = .377).
      CONCLUSIONS: The degree of aspirin effect on platelet aggregability maybe
      important in the management of perioperative CV morbidity, without increment in
      the bleeding toll.

PMID- 24280319
TI  - Linking vitamin B1 with cancer cell metabolism.
AB  - The resurgence of interest in cancer metabolism has linked alterations in the
      regulation and exploitation of metabolic pathways with an anabolic phenotype that
      increases biomass production for the replication of new daughter cells. To
      support the increase in the metabolic rate of cancer cells, a coordinated
      increase in the supply of nutrients, such as glucose and micronutrients
      functioning as enzyme cofactors is required. The majority of co-enzymes are water
      soluble vitamins such as niacin, folic acid, pantothenic acid, pyridoxine,
      biotin, riboflavin and thiamine (Vitamin B1). Continuous dietary intake of these
      micronutrients is essential for maintaining normal health. How cancer cells
      adaptively regulate cellular homeostasis of cofactors and how they can regulate
      expression and function of metabolic enzymes in cancer is underappreciated.
      Exploitation of cofactor-dependent metabolic pathways with the advent of anti
      folates highlights the potential vulnerabilities and importance of vitamins in
      cancer biology. Vitamin supplementation products are easily accessible and
      patients often perceive them as safe and beneficial without full knowledge of
      their effects. Thus, understanding the significance of enzyme cofactors in cancer
      cell metabolism will provide for important dietary strategies and new molecular
      targets to reduce disease progression. Recent studies have demonstrated the
      significance of thiamine-dependent enzymes in cancer cell metabolism. Therefore,
      this review discusses the current knowledge in the alterations in thiamine
      availability, homeostasis, and exploitation of thiamine-dependent pathways by
      cancer cells. 

PMID- 24280325
TI  - Ethanol embolotherapy of foot arteriovenous malformations.
AB  - OBJECTIVE: To review initial clinical presentation, treatment course, and results
      of ethanol embolotherapy for foot arteriovenous malformations (AVMs) and to
      analyze prognostic factors for treatment results. METHODS: Twenty-nine patients
      (mean age, 31.3 years; range, 9-59) who underwent ethanol embolotherapy between
      1999 and 2012 were retrospectively reviewed. Initial clinical manifestation,
      medical history, treatment results of ethanol embolotherapy, and major and minor
      complications were reviewed in detail. Two radiologists analyzed the extent of
      AVM involvement, modified angiographic classification by Cho et al, presence of
      feeding artery aneurysm, degree of devascularization after embolotherapy, and
      treatment results. From the analysis, prognostic factors for final outcome were
      assessed. RESULTS: The most common symptom was pain (83%; 24/29), followed by
      ulcer (52%; 15/29), mass (48%; 14/29), varicosity (38%; 11/29), and swelling
      (31%; 9/29). On baseline angiogram, lesion extent <25% of the foot occurred in
      62% (18/29) of cases. Between 25% and 33% comprised 24% (7/29), followed by more
      than 66% (10%; 3/29) and 33% to 50% (3%; 1/29). The most common modified
      angiographic type was type IIIa (38%; 11/29), followed by IIIb (31%; 9/29), II
      (14%; 4/29), IIIa + IIIb (7%; 2/29), and II + IIIa (3%; 1/29). A total of 61
      ethanol embolization sessions (range, 1-10; median, 1) were performed in 29
      patients. Seventeen of the 29 patients had only one intervention. Transarterial
      approach was performed in six patients and direct puncture in 11 patients. Twelve
      patients required both transarterial approach and direct puncture. One patient
      underwent both coil embolization via direct puncture and transarterial ethanol
      embolotherapy. Cure (as judged by both completion angiography and clinical
      improvement) was achieved in seven patients (24%; 7/29). Seventeen patients
      experienced improvement (59%; 17/29). In three patients, the lesion showed no
      change (10%). Treatment failure was reported in two patients (7%; 2/29). Major
      complications occurred in 24% (7/29) and minor complications in 52% (15/29). Skin
      necrosis (35%; 10/29) was the most common minor complication. Lesion extent had a
      moderate correlation with outcome (P < .001; rho = 0.633). Lesions <25% showed
      100% success rates with >25% having 55%. There was no correlation between
      angiographic type and outcome (P > .05; rho = 0.143). CONCLUSIONS: Ethanol
      embolotherapy for foot AVMs can be as effective and safe as for other body parts.
      From the analysis of angiographic findings, foot AVMs that involve <25% of the
      area of the foot are prone to show better treatment outcomes from ethanol
      embolotherapy.

PMID- 24280326
TI  - Staged hybrid repair for symptomatic extensive aortic aneurysm from distal
      ascending across aortic arch till supraceliac thoracic aorta.

PMID- 24280327
TI  - Bilateral popliteal artery entrapment syndrome in a young man.

PMID- 24280328
TI  - Aberrant origin of left vertebral artery.

PMID- 24280329
TI  - New insights into the physiologic basis for intermittent pneumatic limb
      compression as a therapeutic strategy for peripheral artery disease.
AB  - The capability for externally applied rhythmic limb compressions to improve the
      outcomes of patients with peripheral artery disease has been recognized for
      nearly a century. Modern technology has permitted the development of portable and
      cost-effective intermittent pneumatic compression (IPC) systems to be made
      readily available for affordable at-home use. Mounting clinical evidence attests
      to the effectiveness of this strategy, with improvements in claudication distance
      rivaling those seen with exercise training or pharmacologic interventions, or
      both. However, owing to a lack of mechanistic knowledge, whether current
      application protocols are optimized for clinical outcomes is unknown. Traditional
      thinking has suggested that IPC transiently elevates blood flow, which is
      purported to relieve ischemia, improve vascular function, and promote vascular
      remodeling. Surprisingly, much ambiguity exists regarding the physiologic stimuli
      and adaptations that are responsible for the clinical effectiveness of IPC
      treatment. This review presents and critically discusses emerging evidence that
      sheds new light on the physiologic and molecular responses to IPC therapy. These
      novel findings highlight the importance of characterizing the phasic changes in
      the hemodynamic profile during IPC application. Further, these studies indicate
      that factors other than the elevation in blood flow during this therapy should be
      taken into account when designing an optimal IPC device. Lastly, we advance the
      hypothesis that manipulation of IPC stimulation characteristics could potentially
      magnify the documented clinical benefits associated with this therapy. In
      conclusion, recent evidence challenges the physiologic basis on which current IPC
      systems were designed, and further research to elucidate the basic and clinical
      outcomes of alternate stimulation characteristics is necessary. 

PMID- 24280330
TI  - Transgression confession: ethics of medical error disclosure.
AB  - Complications of medicine are like the sand traps in golf courses. They are
      regrettable, cannot be completely avoided even by the best, and the real skill
      lies in solving the problems they present. Dr Al Mighty told a resident to ignore
      a barely elevated temperature in a postoperative patient. "It is nothing worthy
      of your concern," the Al Mighty said. But, the surgical resident remembered a
      break in operative sterile technique had occurred, about which she remained
      concerned. When an area felt mildly edematous, the wound was probed, and pus
      exuded. The patient asked how this had happened. The resident should respond:
      Keep her mouth shut.B.Tell the patient that wound infections just happen.C.Tell
      the patient that a break in sterile technique was responsible.D.Refer the matter
      to the chief resident for advice.E.Tell the patient to ask the attending surgeon.

PMID- 24280331
TI  - A new staged hybrid total arch repair procedure using a branched proximal
      elephant trunk technique with implantation of stent grafts to the ascending
      aorta.
AB  - We report a new hybrid aortic arch repair procedure for the treatment of
      extensive thoracic aortic aneurysms involving the ascending aorta, arch, and
      descending aorta. In the first stage of this procedure, a "double-barrel tube
      graft" was inserted into the ascending aorta and fixed to the sinotubular
      junction under short-duration cardiopulmonary bypass in normothermia. In the next
      stage, after debranching of the left common carotid artery and left subclavian
      artery, stent grafts were deployed from the double-barrel tube graft to the
      descending aorta and the brachiocephalic artery to exclude the aneurysms. The
      patient's postoperative course was uneventful, with no endoleaks. The successful
      initial result suggests that this procedure could be an attractive treatment
      option for extensive aortic aneurysms. 

PMID- 24280332
TI  - Debate: whether young, good-risk patients should be treated with endovascular
      abdominal aortic aneurysm repair.
AB  - As endovascular abdominal aortic aneurysm repair has become increasingly
      prominent in our vascular surgery practices, the discussion regarding long-term
      durability continues. The initial randomized trials that enrolled patients almost
      10 years ago revealed a short-term survival advantage with endovascular abdominal
      aortic aneurysm repair at the expense of a higher reintervention rate and loss of
      that initial survival advantage in the longer term. Continuing and healthy debate
      over the practical importance of these findings has resulted in somewhat
      differing practice patterns on either side of the Atlantic. This debate explores
      the issues surrounding whether younger, good-risk patients with a long life
      expectancy should be treated with endovascular repair. 

PMID- 24280333
TI  - Editors' commentary.

PMID- 24280334
TI  - Comparison of outcomes following endovascular repair of abdominal aortic
      aneurysms based on size threshold.

PMID- 24280335
TI  - Reply: To PMID 23395206.

PMID- 24280336
TI  - Regarding "hybrid repair of aortic arch dissections".

PMID- 24280337
TI  - Regarding "validation of three models predicting in-hospital death in patients
      with an abdominal aortic aneurysm eligible for both endovascular and open
      repair".

PMID- 24280338
TI  - Regarding "intra-arterial injection of acrylic cement as a complication of
      percutaneous vertebroplasty".

PMID- 24280339
TI  - Health situation and issues in the Seychelles in 2012.
AB  - Located off the coast of Kenya, the Republic of the Seychelles is an island
      archipelago nation whose citizens are mostly of African origin. The population,
      independent from the United Kingdom since 1976, has largely completed its
      demographic and epidemiological transitions. Major investments in infrastructure
      and social services have fostered a steady economic growth. Health services and
      education are free. The predominance of chronic non-communicable diseases and
      rapid aging of the population cause significant new challenges for public health
      and the health system. However, like the other small island states in the region,
      the Seychelles remains under the threat of outbreaks, particularly of
      arboviruses. Health indicators from 2012 are generally very good. There are
      concerns, however, about the future of health care in the country. Geographic
      isolation, the small and aging population and limited resources provide major
      challenges for maintaining and sustaining an effective workforce of health
      professionals, a constantly evolving technical platform and an increasing number
      of available medications. This is true particularly in view of the increasing
      burden of chronic diseases and the continued threat to the population of current
      or emerging infectious diseases. The purpose of this article is to provide a
      brief introduction to the geography, history, and political context of Seychelles
      to provide an account of the current situation regarding major diseases in the
      Seychelles and to review health priorities of the last few decades. To our
      knowledge, no comprehensive inventory of sporadic, endemic or epidemic events has
      been attempted before, except for a remarkable report from the 1950s [1]. Using
      health data from the past few decades, information from health personnel who live
      and practice in the Indian Ocean, we attempt to identify major current and future
      health challenges in the Seychelles.

PMID- 24280340
TI  - DNA cleavage induced by [Cu(L)x(NO3)2] (L=2,2'-dipyridylamine, 2,2'-bipyridine,
      dipicolylamine, x=1 or 2): Effect of the ligand structure.
AB  - The efficiency of [Cu(2,2'-bipyridine)2(NO3)]NO3, [Cu(2,2'
      dipyridylamine)2(NO3)2], and [Cu(dipicolylamine)2(NO3)2] complexes (complex 1, 2
      and 3, respectively) in oxidative DNA cleavage was examined by electrophoresis
      and linear dichroism (LD). Among the three Cu complexes, complex 1 showed the
      highest efficiency in super-coiled DNA (scDNA) cleavage in electrophoresis. The
      presence of tiron, a superoxide radical scavenger, suppressed the reaction almost
      completely. The LD signal at 260 nm decreased gradually as the time passed. The
      decrease in LD magnitude was explained best by the sum of the two single
      exponential curves. This suggests that the cleavage reaction involves two first
      order kinetic processes; an increase in flexibility due to scission of one of the
      strands and a shortening in the DNA stem due to cut of both strands of double
      stranded DNA (dsDNA). In agreement with the electrophoresis data, complex 1
      exhibited the highest efficiency with the superoxide radical found to be the
      essential reactive oxygen species. The order of efficiency in both scDNA and
      dsDNA was as follows: complex 1>complex 2>complex 3. The electrochemical
      properties alone were insufficient to explain the observed efficiencies, even
      though reduction of the central Cu ion is essential for the oxidative DNA
      cleavage. This highlights the importance of an ability to ligate the molecular
      oxygen (or hydrogen peroxide) to the central Cu ion to produce the superoxide
      radical, in addition to the reduction of Cu ion, in oxidative DNA cleavage.

PMID- 24280341
TI  - Promoting community participation in priority setting in district health systems:
      experiences from Mbarali district, Tanzania.
AB  - BACKGROUND: Community participation in priority setting in health systems has
      gained importance all over the world, particularly in resource-poor settings
      where governments have often failed to provide adequate public-sector services
      for their citizens. Incorporation of public views into priority setting is
      perceived as a means to restore trust, improve accountability, and secure cost
      effective priorities within healthcare. However, few studies have reported
      empirical experiences of involving communities in priority setting in developing
      countries. The aim of this article is to provide the experience of implementing
      community participation and the challenges of promoting it in the context of
      resource-poor settings, weak organizations, and fragile democratic institutions.
      DESIGN: Key informant interviews were conducted with the Council Health
      Management Team (CHMT), community representatives, namely women, youth, elderly,
      disabled, and people living with HIV/AIDS, and other stakeholders who
      participated in the preparation of the district annual budget and health plans.
      Additionally, minutes from the Action Research Team and planning and priority
      setting meeting reports were analyzed. RESULTS: A number of benefits were
      reported: better identification of community needs and priorities, increased
      knowledge of the community representatives about priority setting, increased
      transparency and accountability, promoted trust among health systems and
      communities, and perceived improved quality and accessibility of health services.
      However, lack of funds to support the work of the selected community
      representatives, limited time for deliberations, short notice for the meetings,
      and lack of feedback on the approved priorities constrained the performance of
      the community representatives. Furthermore, the findings show the importance of
      external facilitation and support in enabling health professionals and community
      representatives to arrive at effective working arrangement. CONCLUSION: Community
      participation in priority setting in developing countries, characterized by weak
      democratic institutions and low public awareness, requires effective mobilization
      of both communities and health systems. In addition, this study confirms that
      community participation is an important element in strengthening health systems.

PMID- 24280342
TI  - Activation of paraoxonase 1 is associated with HDL remodeling ex vivo.
AB  - BACKGROUND: We hypothesize that during high density lipoprotein (HDL) remodeling
      PON1 reaches an optimal distribution in HDL subclasses by which it achieves
      maximum activity. We conducted this study to gain insight on PON1 fate and
      activation during short-term HDL remodeling ex vivo. METHODS: Serum from 8
      healthy volunteers was either frozen at -80 degrees C (time 0) or incubated under
      sterile conditions for up to 48h at 37 degrees C or at 4 degrees C. Aliquots were
      taken at 3, 6, 9, 24 and 48 h and immediately frozen at -80 degrees C. PON1
      activities were measured, as well as PON1 and apolipoprotein distributions in HDL
      subclasses by gradient gel electrophoresis. RESULTS: The first novel finding in
      our study is the evidence provided for a significant activation of both lactonase
      and arylesterase activities of PON1 that ensues in a very short time frame of
      incubation of serum ex vivo at 37 degrees C. All subjects studied displayed these
      changes, the activation was apparent in <3h, peaked at 6h and amounted to >20%.
      This is associated with a temperature and time-dependent redistribution of PON1
      activity in HDL subclasses, with an increase in activity in both very large HDL2
      and small HDL3 in the first phase (3-9h), followed by a progressive transfer of
      PON1 to very large HDL2 as the particles mature. These changes are paralleled by
      the appearance of weak, but apparent PON1 activity at subspecies that correspond
      to sdLDL. During the first phase of PON1 activation and shifts, a parallel shift
      of apoE can be evidenced: at 3-9h, apoE increases in sdLDL, after that time it is
      lost from HDL and also from sdLDL and stays in VLDL at the origin of the run.
      ApoA-I shifts towards larger particles, which parallels the change in PON1. As
      HDL matures there is a progressive shift of apoA-II towards larger HDL. Low
      levels of apoA-IV at the initiation of the incubation are followed by time
      dependent quick disappearance of apoA-IV in HDL which parallels the changes in
      PON1, apoE and A-II. CONCLUSION: Short, ex vivo incubation of serum leads to
      quick activation of PON1 associated with transfers to HDL3c, large HDL and sdLDL.
      The process is blocked by CETP and LCAT inhibitors. The data suggest that HDL
      maturation optimizes PON1 activity. These findings may be of interest for future
      studies aimed at modulating PON-1 activity for its cardioprotective effects and
      suggest a new mechanism whereby CETP inhibitors failed in clinical trials.

PMID- 24280343
TI  - Complete A-V block: incidental or a part of cor triatriatum dexter.
AB  - Cor triatriatum dexter (CTD) is an extremely rare cardiac anomaly in which the
      right atrium is divided into two distinct chambers by a membrane. The persistence
      of the right valve of sinus venosus results in a complete septation of the right
      atrium. This anomaly is frequently associated with other right-sided cardiac
      abnormalities. Its clinical manifestation and the need for intervention are
      determined by the number and the size of the fenestrations on the membrane,
      associated cardiac anomalies and arrhythmias. We describe a case of CTD in a
      patient with complete atrioventricular (A-V) block. 

PMID- 24280344
TI  - Cilostazol decreases total atrial conduction time in patients with peripheral
      artery disease.
AB  - OBJECTIVE: Total atrial conduction time (TACT) is the most important parameter in
      predicting the development of new-onset atrial fibrillation. We investigated the
      effect of cilostazol therapy on TACT in patients with peripheral artery disease.
      METHODS: Thirty patients with peripheral artery disease were treated with
      cilostazol (200 mg/day) for 6 months. The baseline echocardiographic total atrial
      conduction time parameter was compared with the 6-month follow-up. RESULTS: The
      TACT duration was decreased in all patients compared with the baseline after
      therapy (121.8 +/- 19.3 vs. 109.1 +/- 15.9 milliseconds, p<0.001). However, left
      atrial (LA) diameter was not changed with the therapy. The reduction of TACT
      duration was correlated with the increase in mitral E wave velocity/mitral A wave
      velocity ratio (r=-0.48, p<0.003). CONCLUSION: Our results showed that 200 mg
      cilostazol treatment decreased TACT duration in patients with peripheral artery
      disease, which may also prevent the development and/or recurrence of atrial
      fibrillation (AF).

PMID- 24280346
TI  - Diversity and genetics of nitrogen-induced susceptibility to the blast fungus in
      rice and wheat.
AB  - BACKGROUND: Nitrogen often increases disease susceptibility, a phenomenon that
      can be observed under controlled conditions and called NIS, for Nitrogen-Induced
      Susceptibility. NIS has long been reported in the case of rice blast disease
      caused by the fungus Magnaporthe oryzae. We used an experimental system that does
      not strongly affect plant development to address the question of NIS polymorphism
      across rice diversity and further explored this phenomenon in wheat. We tested
      the two major types of resistance, namely quantitative/partial resistance and
      resistance driven by known resistance genes. Indeed there are conflicting reports
      on the effects of NIS on the first one and none on the last one. Finally, the
      genetics of NIS is not well documented and only few loci have been identified
      that may control this phenomenon. RESULTS: Our data indicate that NIS is a
      general phenomenon affecting resistance to blast fungus in these two cereals. We
      show that the capacity of rice to display NIS is highly polymorphic and does not
      correlate with difference related to indica/japonica sub-groups. We also tested
      the robustness of three different major resistance genes under high nitrogen.
      Nitrogen partially breaks down resistance triggered by the Pi1 gene. Cytological
      examination indicates that penetration rate is not affected by high nitrogen
      whereas growth of the fungus is increased inside the plant. Using the CSSL
      mapping population between Nipponbare and Kasalath, we identified a Kasalath
      locus on chromosome 1, called NIS1, which dominantly increases susceptibility
      under high nitrogen. We discuss the possible relationships between Nitrogen Use
      Efficiency (NUE), disease resistance regulation and NIS. CONCLUSIONS: This work
      provides evidences that robust forms of partial resistance exist across diversity
      and can be easily identified with our protocol. This work also suggests that
      under certain environmental circumstances, complete resistance may breakdown,
      irrelevantly of the capacity of the fungus to mutate. These aspects should be
      considered while breeding for robust forms of resistance to blast disease.

PMID- 24280345
TI  - A genome scale metabolic network for rice and accompanying analysis of
      tryptophan, auxin and serotonin biosynthesis regulation under biotic stress.
AB  - BACKGROUND: Functional annotations of large plant genome projects mostly provide
      information on gene function and gene families based on the presence of protein
      domains and gene homology, but not necessarily in association with gene
      expression or metabolic and regulatory networks. These additional annotations are
      necessary to understand the physiology, development and adaptation of a plant and
      its interaction with the environment. RESULTS: RiceCyc is a metabolic pathway
      networks database for rice. It is a snapshot of the substrates, metabolites,
      enzymes, reactions and pathways of primary and intermediary metabolism in rice.
      RiceCyc version 3.3 features 316 pathways and 6,643 peptide-coding genes mapped
      to 2,103 enzyme-catalyzed and 87 protein-mediated transport reactions. The
      initial functional annotations of rice genes with InterPro, Gene Ontology,
      MetaCyc, and Enzyme Commission (EC) numbers were enriched with annotations
      provided by KEGG and Gramene databases. The pathway inferences and the network
      diagrams were first predicted based on MetaCyc reference networks and plant
      pathways from the Plant Metabolic Network, using the Pathologic module of Pathway
      Tools. This was enriched by manually adding metabolic pathways and gene functions
      specifically reported for rice. The RiceCyc database is hierarchically browsable
      from pathway diagrams to the associated genes, metabolites and chemical
      structures. Through the integrated tool OMICs Viewer, users can upload
      transcriptomic, proteomic and metabolomic data to visualize expression patterns
      in a virtual cell. RiceCyc, along with additional species-specific pathway
      databases hosted in the Gramene project, facilitates comparative pathway
      analysis. CONCLUSIONS: Here we describe the RiceCyc network development and
      discuss its contribution to rice genome annotations. As a case study to
      demonstrate the use of RiceCyc network as a discovery environment we carried out
      an integrated bioinformatic analysis of rice metabolic genes that are
      differentially regulated under diurnal photoperiod and biotic stress treatments.
      The analysis of publicly available rice transcriptome datasets led to the
      hypothesis that the complete tryptophan biosynthesis and its dependent metabolic
      pathways including serotonin biosynthesis are induced by taxonomically diverse
      pathogens while also being under diurnal regulation. The RiceCyc database is
      available online for free access at http://www.gramene.org/pathway/.

PMID- 24280347
TI  - Developmental trajectory from early responses to transgressions to future
      antisocial behavior: evidence for the role of the parent-child relationship from
      two longitudinal studies.
AB  - Parent-child relationships are critical in development, but much remains to be
      learned about the mechanisms of their impact. We examined the early parent-child
      relationship as a moderator of the developmental trajectory from children's
      affective and behavioral responses to transgressions to future antisocial,
      externalizing behavior problems in the Family Study (102 community mothers,
      fathers, and infants, followed through age 8) and the Play Study (186 low-income,
      diverse mothers and toddlers, followed for 10 months). The relationship quality
      was indexed by attachment security in the Family Study and maternal
      responsiveness in the Play Study. Responses to transgressions (tense discomfort
      and reparation) were observed in laboratory mishaps wherein children believed
      they had damaged a valued object. Antisocial outcomes were rated by parents. In
      both studies, early relationships moderated the future developmental trajectory:
      diminished tense discomfort predicted more antisocial outcomes, but only in
      insecure or unresponsive relationships. That risk was defused in secure or
      responsive relationships. Moderated mediation analyses in the Family Study
      indicated that the links between diminished tense discomfort and future
      antisocial behavior in insecure parent-child dyads were mediated by stronger
      discipline pressure from parents. By indirectly influencing future developmental
      sequelae, early relationships may increase or decrease the probability that the
      parent-child dyad will embark on a path toward antisocial outcomes. 

PMID- 24280349
TI  - Maize developmental stage affects indirect and direct defense expression.
AB  - Herbivores elicit a complex indirect and direct defense response in plants, but
      little is known about how defenses are expressed throughout a plant's life cycle.
      Here we report the characterization of direct and indirect defense profiles for
      two vegetative stages of maize, v1 and v3. Indirect defense expression was
      evaluated by measuring plant headspace volatiles in response to artificial
      herbivory and caterpillar feeding. To assess direct defense expression,
      transcripts of four proteinase inhibitors (PI) and larval performance were
      measured. Artificial herbivory significantly elevated total induced volatiles in
      v1 and v3 compared with controls, but this induction was marginal in v1 when
      compared with v3. Both maize stages produced similar total amounts of volatiles,
      accounting for fresh weight, of different compositions during caterpillar
      feeding. However, on a per-plant basis, v1 produced less volatiles compared with
      v3. In contrast, jasmonic acid levels, an indicator of an antiherbivore defense
      response, increased similarly in both stages. During caterpillar feeding, both
      developmental stages contained higher levels of PI transcripts compared with
      controls. However, v1 plants contained more cystatin-like PI transcripts and
      total larval mass was reduced compared with v3 plants. These results suggest that
      in maize, direct and indirect defenses against insect herbivory differ between
      seedling and juvenile plants. 

PMID- 24280348
TI  - Gefitinib resistance resulted from STAT3-mediated Akt activation in lung cancer
      cells.
AB  - Hyperactivation of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase is
      prevalent in human lung cancer and its inhibition by the tyrosine kinase
      inhibitors (TKIs), including gefitinib and erlotinib, initially controls tumor
      growth. However, most patients ultimately relapse due to the development of drug
      resistance. In this study, we have discovered a STAT3-dependent Akt activation
      that impairs the efficacy of gefitinib. Mechanistically, gefitinib increased
      association of EGFR with STAT3, which de-repressed STAT3 from SOCS3, an upstream
      suppressor of STAT3. Such a de-repression of STAT3 in turn fostered Akt
      activation. Genetic or pharmacological inhibition of STAT3 abrogated Akt
      activation and combined gefitinib with STAT3 inhibition synergistically reduced
      the growth of the tumor cells. Taken together, this study suggests that
      activation of STAT3 is an intrinsic mechanism of drug resistance in response to
      EGFR TKIs. Combinational targeting on both EGFR and STAT3 may enhance the
      efficacy of gefitinib or other EGFR TKIs in lung cancer.

PMID- 24280350
TI  - Prefrontal cortex volume deficit in schizophrenia: a new look using 3T MRI with
      manual parcellation.
AB  - In this study we use high resolution Magnetic Resonance imaging (MRI) and apply
      rigorous manual tracing criteria in order to assess volumetrically the prefrontal
      cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in
      neural systems necessary for emotional processing and cognition, and regional PFC
      abnormalities might, thus, lead to specific negative symptoms, as well as a
      frequent association of poorer performance in category switching. The aim of this
      study was to use 3T imaging and reliable manual parcellation to determine if, as
      hypothesized, this higher precision would reveal additional MRI abnormalities in
      PFC in schizophrenia, and an association between PFC abnormalities and specific
      negative symptoms, as well as in category switching. Using 3-T MRI, 27
      schizophrenia patients and 27 healthy controls were examined. PFC was manually
      parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus
      (MFG), and inferior frontal gyrus (IFG). Left SFG (p=0.004), bilateral MFG (left:
      p=0.007; right: p=0.007), and bilateral IFG (left: p<0.001; right: p=0.002)
      showed volume reduction. There were symptom associations between smaller left MFG
      volumes and more affective flattening (R=-0.465, p=0.015), and smaller left IFG
      volumes and poorer performance on the alternating semantic category test
      (R=0.440, p=0.025). In summary, 3-T imaging revealed widespread gyral volume
      deficits in PFC gyri, and specific associations with selective negative symptoms,
      such as affective flattening, and with deficits in cognitive switching. 

PMID- 24280351
TI  - Biomechanical comparison of reverse total shoulder arthroplasty systems in soft
      tissue-constrained shoulders.
AB  - BACKGROUND: Numerous studies have examined the biomechanics of isolated variables
      in reverse total shoulder arthroplasty. This study directly compared the
      composite performance of two reverse total shoulder arthroplasty systems; each
      system was designed around either a medialized or a lateralized glenohumeral
      center of rotation. METHODS: Seven pairs of shoulders were tested on a
      biomechanical simulator. Center of rotation, position of the humerus, passive and
      active range of motion, and force to abduct the arm were quantified. Native arms
      were tested, implanted with a Tornier Aequalis or DJO Surgical Reverse Shoulder
      Prosthesis (RSP), and then retested. Differences from the native state were then
      documented. RESULTS: Both systems shifted the center of rotation medially and
      inferiorly relative to native. Medial shifts were greater in the Aequalis implant
      (P < .037). All humeri shifted inferior compared with native but moved medially
      with the Aequalis (P < .001). Peak passive abduction, internal rotation, and
      external rotation did not differ between systems (P > .05). Both reverse total
      shoulder arthroplasty systems exhibited adduction deficits, but the RSP implant
      deficit was smaller (P = .046 between implants). Both systems reduced forces to
      abduct the arm compared with native, although the Aequalis required more force to
      initiate motion from the resting position (P = .022). CONCLUSION: Given the
      differences in system designs and configurations, outcome variables were
      generally comparable. The RSP implant allowed slightly more adduction, had a more
      lateralized humeral position, and required less force to initiate elevation.
      These factors may play roles in limiting scapular notching, improving active
      external rotation by normalizing the residual rotator cuff length, and limiting
      excessive stress on the deltoid.

PMID- 24280352
TI  - Revisit to scapular dyskinesis: three-dimensional wing computed tomography in
      prone position.
AB  - BACKGROUND: Three-dimensional (3D) wing computed tomography (CT) showed a high
      inter-rater reliability in assessing scapular dyskinesis. METHODS: The 330
      scapular movements of 165 patients were classified into 4 types by 7 blinded
      observers. Then, 3D wing CT was performed with patients prone, and 4 blinded
      observers measured 5 angles, consisting of upward rotation (UR) superior
      translation (ST), anterior tilting (AT), protraction (PRO), and internal rotation
      (IR). The inter-rater reliability (IRR) of 2 methods was calculated, and cutoff
      values were determined for the 5 angles on the 3D wing CT images. RESULTS: The
      IRR was 0.783 for the observational method of scapular dyskinesis and 0.981 for
      3D wing CT in the prone position. UR and ST angles were significantly larger in
      type 3 more than in the other types (P < .001, P < .001), and the AT angle showed
      a similar pattern in type 1 (P < .001). The PRO angle was significantly larger in
      types 1, 2, and 3 more than in type 4 (P < .001, P < .001, P = .013), and the IR
      angle was significantly larger in type 2 more than in the other types (P < .001).
      The cutoff values of the 5 angles were UR, 117 degrees ; ST, 90 degrees ; AT, 8
      degrees ; PRO, 99 degrees ; and IR, 51 degrees . The UR angle showed a
      significant correlation with glenohumeral internal rotation deficit (odds ratio,
      0.436; P = .029) and the IR angle with MDI (odds ratio, 8.947; P = .048).
      CONCLUSION: The patients with a high UR angle showed a low rate of glenohumeral
      internal rotation deficit and those with a high IR angle had a high rate of the
      MDI in affected shoulder by the determinant of the cutoff value of the 5 angles.
      LEVEL OF EVIDENCE: Level III, development of diagnostic criteria with
      nonconsecutive patients, diagnostic study.

PMID- 24280353
TI  - Scapulothoracic fusion: outcomes and complications.
AB  - BACKGROUND: Scapulothoracic fusion (STF) may be an option to alleviate pain and
      restore function. The purpose of this study is to report the clinical outcome of
      patients who underwent STF for the treatment of painful scapular winging.
      MATERIALS AND METHODS: From 1999 through 2008, 10 patients (12 shoulders)
      underwent an STF for painful winging of the scapula. The mean follow-up period
      was 41 months (range, 8-72 months). Indications for STF included winging in
      association with excessive medial and/or lateral clavicular resection and
      facioscapulohumeral dystrophy, as well as scapular winging related to combined
      long thoracic and spinal accessory nerve palsy. A retrospective review was
      performed to evaluate the subjective shoulder value, visual analog scale score,
      range of motion, unions, and complications. RESULTS: There was a statistically
      significant improvement in the subjective shoulder value, visual analog scale
      score, range of motion, and satisfaction postoperatively. The overall
      complication rate was 50% (6 of 12). There were 2 persistent nonunions (2 of 12,
      17%), and 50% (6 of 12) of all fusions required subsequent hardware removal
      because of discomfort. Complications included pleural effusion (3 of 12, 25%),
      hemopneumothorax (1 of 12, 8%) pulmonary embolus (1 of 12, 8%), and infection (1
      of 12, 8%). With the exception of the revision nonunion, all complications
      resolved with no negative sequelae. CONCLUSION: STF results in improved function
      and pain relief. STF is associated with a high short-term complication rate with
      limited long-term sequelae.

PMID- 24280354
TI  - Dominance effect on scapula 3-dimensional posture and kinematics in healthy male
      and female populations.
AB  - BACKGROUND: The contralateral shoulder is often used as a reference when
      evaluating a pathologic shoulder. However, the literature provides contradictory
      results regarding the symmetry of the scapular pattern in a healthy population.
      We assume that several factors including gender and type of motion may influence
      the bilateral symmetry of the scapulae. MATERIALS AND METHODS: The dominant and
      nondominant shoulders of 2 populations of men and women comprising 11 subjects
      each were evaluated for 3 distinct motions: flexion in the sagittal plane,
      abduction in the frontal plane, and glenohumeral internal/external rotation with
      the arm abducted at 90 degrees . Posture, kinematics, and range of motion were
      studied separately. RESULTS: Asymmetries are observed for motions performed in
      the frontal and sagittal plane but not for internal/external rotation with the
      arm abducted at 90 degrees . For both male and female populations, multiplanar
      asymmetries are observed and the dominant scapula has a larger upward rotation.
      The asymmetries mainly originate in the scapula's kinematics and not in its
      original posture. CONCLUSION: Small but significant asymmetries exist between the
      dominant and nondominant shoulders in terms of kinematics. One should be aware of
      these differences when using the contralateral shoulder as a reference. LEVEL OF
      EVIDENCE: Basic science study, kinematics

PMID- 24280355
TI  - Effect of glenoid cementation on total shoulder arthroplasty for degenerative
      arthritis of the shoulder: a review of the New Zealand National Joint Registry.
AB  - BACKGROUND: Despite the lack of literature showing improved results compared with
      cemented designs, uncemented glenoid components are still commonly used in total
      shoulder arthroplasty (TSA). Most studies comparing cemented with uncemented
      glenoids involve small numbers or include patients with inflammatory arthritis.
      METHODS: New Zealand National Joint Registry data was used to compare the
      outcomes of uncemented and cemented glenoids in TSA performed for degenerative
      arthritis. Measured variables were the revision rate and the Oxford Shoulder
      Score (OSS). RESULTS: Data were retrieved on 1596 patients, with a mean follow-up
      3.5 years (range 2-10.7 years), 1065 of whom had a cemented glenoid. There were
      no significant differences in any preoperative factors between the 2 groups. The
      revision rate for uncemented glenoids was 4.4 times higher than for cemented
      glenoids (1.92 vs. 0.44 revisions per 100 component-years, P < .001). Age <55
      years was an independent risk factor for revision (P < .001). The most common
      reason for revision was rotator cuff wear (35.5%) in the uncemented glenoids and
      loosening (36.3%) in the cemented glenoids. The difference in the mean OSS
      between the 2 groups was less than 1 point at 6 months (P = .109) and at 5 years
      (P = .377). CONCLUSION: Uncemented glenoids had a markedly higher revision rate.
      Patients aged <55 years have the highest revision rate regardless of glenoid
      fixation method. The higher revision rate in the uncemented glenoid group
      persisted when the effect of young age was corrected for. There was no clinically
      or statistically significant difference in the OSS results for clinical outcome
      between the two groups. LEVEL OF EVIDENCE: Level III, retrospective cohort,
      treatment study.

PMID- 24280357
TI  - Vulval oedema: how many doctors does it take to make a diagnosis?

PMID- 24280356
TI  - Ets-1 global gene expression profile reveals associations with metabolism and
      oxidative stress in ovarian and breast cancers.
AB  - BACKGROUND: The Ets-1 proto-oncogene is frequently upregulated in cancer cells,
      with known involvement in cancer angiogenesis, metastasis, and more recently
      energy metabolism. In this study we have performed various bioinformatic analyses
      on existing microarray data to further clarify the role of Ets-1 in ovarian
      cancer, and validated these results with functional assays. METHODS: Functional
      pathway analyses were conducted on existing microarray data comparing 2008 and
      2008-Ets1 ovarian cancer cells. Methods included over-representation analysis,
      functional class scoring and pathway topology, and network representations were
      visualized in Cytoscape. Oxidative stress regulation was examined in ovarian
      cancer cells by measuring protein expression and enzyme activity of glutathione
      peroxidases, as well as intracellular reactive oxygen species using
      dichlorofluorescin fluorescence. A stable Ets-1 knockdown MDA-MB-231 cell line
      was created using short hairpin RNA, and glycolytic dependence of these cells was
      measured following treatment with 2-deoxy-D-glucose and Hoechst nuclear staining
      to determine cell number. High-resolution respirometry was performed to measure
      changes in basal oxygen flux between MDA-MB-231 cells and MDA-Ets1KD variants.
      RESULTS: Enrichments in oxidoreductase activity and various metabolic pathways
      were observed upon integration of the different analyses, suggesting that Ets-1
      is important in their regulation. As oxidative stress is closely associated with
      these pathways, we functionally validated our observations by showing that Ets-1
      overexpression resulted in decreased reactive oxygen species with increased
      glutathione peroxidase expression and activity, thereby regulating cellular
      oxidative stress. To extend our findings to another cancer type, we developed an
      Ets-1 knockdown breast cancer cell model, which displayed decreased glycolytic
      dependence and increased oxygen consumption following Ets-1 knockdown confirming
      our earlier findings. CONCLUSIONS: Collectively, this study confirms the
      important role of Ets-1 in the regulation of cancer energy metabolism in ovarian
      and breast cancers. Furthermore, Ets-1 is a key regulator of oxidative stress in
      ovarian cancer cells by mediating alterations in glutathione antioxidant
      capacity.

PMID- 24280358
TI  - Respiratory safety pharmacology - current practice and future directions.
AB  - Current practice in respiratory safety pharmacology generally follows the
      guidance provided by the ICH document S7A and, in general, focuses on measures of
      pulmonary ventilation. Respiratory rate, tidal volume and/or a measure of
      arterial blood gases are the recommended ventilatory measurement parameters.
      Although these parameters will provide a measure of ventilation, other
      ventilatory parameters, which can provide mechanistic insight, should also be
      considered. Such parameters include inspiratory and expiratory times and flows
      and apneic time. Stimulation models involving exercise and exposure to elevated
      CO2 or reduced O2 should also be considered when enhancing measurement
      sensitivity or quantifying reductions in ventilatory functional reserve are
      desired. Although ventilatory measurements are capable of assessing the
      functional status of the respiratory pumping apparatus, such measurements are
      generally not capable of assessing the status of the other functional component
      of the respiratory system, namely, the gas exchange unit or lung. To characterize
      drug-induced effects on the gas exchange unit, measures of airway patency, lung
      elastic recoil and gas diffusion capacity need to be considered. Thus, a variety
      of methodologies and measurement endpoints are available for detecting and
      characterizing drug-induced respiratory dysfunction in animal models and should
      be considered when designing respiratory safety pharmacology studies. 

PMID- 24280359
TI  - Approaches and considerations for the assessment of immunotoxicity for
      environmental chemicals: a workshop summary.
AB  - As experience is gained with toxicology testing and as new assays and
      technologies are developed, it is critical for stakeholders to discuss
      opportunities to advance our overall testing strategies. To facilitate these
      discussions, a workshop on practices for assessing immunotoxicity for
      environmental chemicals was held with the goal of sharing perspectives on
      immunotoxicity testing strategies and experiences, developmental immunotoxicity
      (DIT), and integrated and alternative approaches to immunotoxicity testing.
      Experiences across the chemical and pharmaceutical industries suggested that
      standard toxicity studies, combined with triggered-based testing approaches,
      represent an effective and efficient approach to evaluate immunotoxic potential.
      Additionally, discussions on study design, critical windows, and new guideline
      approaches and experiences identified important factors to consider before
      initiating DIT evaluations including assay choice and timing and the impact of
      existing adult data. Participants agreed that integrating endpoints into standard
      repeat-dose studies should be considered for fulfilling any immunotoxicity
      testing requirements, while also maximizing information and reducing animal use.
      Participants also acknowledged that in vitro evaluation of immunosuppression is
      complex and may require the use of multiple assays that are still being
      developed. These workshop discussions should contribute to developing an
      effective but more resource and animal efficient approach for evaluating chemical
      immunotoxicity. 

PMID- 24280360
TI  - Hysteroscopy in pregnancy-related conditions: descriptive analysis in 273
      patients.
AB  - STUDY OBJECTIVE: To describe the feasibility of office hysteroscopy in patients
      with pregnancy-related problems such as retained trophoblastic tissue, persistent
      molar tissue, pregnancy with in situ intrauterine device (IUD), isthmocele,
      embryoscopy, and osseous metaplasia. DESIGN: Retrospective cohort chart review of
      use of hysteroscopy in 273 patients with pregnancy-related conditions (Canadian
      Task Force classification II-2). SETTING: University tertiary-care hospital.
      PATIENTS: Office hysteroscopy with the indication of pregnancy-related conditions
      such as retained trophoblastic tissue, pregnancy with IUD, molar pregnancy,
      cesarean scar defects, and fetal death were studied. The study included 273
      patients: 185 with retained trophoblastic tissue, 14 with persistent molar
      tissue, 7 with an in situ IUD, 22 with symptomatic isthmocele, 41 with
      embryoscopy, and 4 with osseous metaplasia. INTERVENTION: Diagnostic and
      operative office hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Variables studied
      included resolution of abnormal uterine bleeding in patients with persistent
      trophoblastic tissue, normalization of beta-human chorionic gonadotropin levels
      in patients with persistent molar tissue, continuation of pregnancy after
      retrieval of lost IUDs, resolution of postmenstrual bleeding in patients with
      symptomatic isthmocele, rate of uncontaminated embryonic tissue after
      embryoscopic biopsy, and successful extraction of bony tissue in patients with
      osseous metaplasia. Office hysteroscopy enabled resolution of most cases of
      retained trophoblastic tissue (91.8%) and all 14 cases of persistent molar
      tissue. 7 IUDs were extracted from pregnant patients. Fifteen isthmoceles
      resolved with office hysteroscopy, and 7 were resected in the operating room. A
      normal karyotype was obtained in 37 embryoscopies (90.2%). Four osseous
      metaplasia cases resolved with either office hysteroscopy (75%) or resectoscopy
      in the operating room (25%). CONCLUSION: Office hysteroscopy is a safe and
      minimally invasive treatment for pregnancy-related conditions, with good clinical
      and functional results.

PMID- 24280361
TI  - Often wrong but never in doubt.

PMID- 24280362
TI  - Resolving ancient radiations: can complete plastid gene sets elucidate deep
      relationships among the tropical gingers (Zingiberales)?
AB  - BACKGROUND AND AIMS: Zingiberales comprise a clade of eight tropical monocot
      families including approx. 2500 species and are hypothesized to have undergone an
      ancient, rapid radiation during the Cretaceous. Zingiberales display substantial
      variation in floral morphology, and several members are ecologically and
      economically important. Deep phylogenetic relationships among primary lineages of
      Zingiberales have proved difficult to resolve in previous studies, representing a
      key region of uncertainty in the monocot tree of life. METHODS: Next-generation
      sequencing was used to construct complete plastid gene sets for nine taxa of
      Zingiberales, which were added to five previously sequenced sets in an attempt to
      resolve deep relationships among families in the order. Variation in taxon
      sampling, process partition inclusion and partition model parameters were
      examined to assess their effects on topology and support. KEY RESULTS: Codon
      based likelihood analysis identified a strongly supported clade of ((Cannaceae,
      Marantaceae), (Costaceae, Zingiberaceae)), sister to (Musaceae, (Lowiaceae,
      Strelitziaceae)), collectively sister to Heliconiaceae. However, the deepest
      divergences in this phylogenetic analysis comprised short branches with weak
      support. Additionally, manipulation of matrices resulted in differing deep
      topologies in an unpredictable fashion. Alternative topology testing allowed
      statistical rejection of some of the topologies. Saturation fails to explain
      observed topological uncertainty and low support at the base of Zingiberales.
      Evidence for conflict among the plastid data was based on a support metric that
      accounts for conflicting resampled topologies. CONCLUSIONS: Many relationships
      were resolved with robust support, but the paucity of character information
      supporting the deepest nodes and the existence of conflict suggest that plastid
      coding regions are insufficient to resolve and support the earliest divergences
      among families of Zingiberales. Whole plastomes will continue to be highly useful
      in plant phylogenetics, but the current study adds to a growing body of
      literature suggesting that they may not provide enough character information for
      resolving ancient, rapid radiations.

PMID- 24280363
TI  - The comparative effects of clozapine versus haloperidol on initiation and
      maintenance of alcohol drinking in male alcohol-preferring P rat.
AB  - Alcohol use disorder, characterized by modest levels of alcohol use, commonly
      occurs in patients with schizophrenia and dramatically worsens their course.
      Recent data indicate that the atypical antipsychotic clozapine, but not the
      typical antipsychotic haloperidol, decreases alcohol drinking both in patients
      with schizophrenia and also in the Syrian golden hamster, an animal model of
      moderate alcohol drinking. The present study was designed to assess the
      comparative effects of clozapine and haloperidol in the alcohol-preferring (P)
      rat, an animal model of alcoholism. First, the study investigated the comparative
      effects of clozapine and haloperidol on initiation of alcohol consumption in P
      rats, which models the early stage of alcoholism. Second, the study assessed the
      comparative effects of clozapine and haloperidol on maintenance of chronic
      alcohol consumption in P rats to provide a clue as to whether either drug may
      also limit alcohol consumption in alcohol-dependent patients. Clozapine
      attenuated the initiation of alcohol drinking and development of alcohol
      preference while haloperidol did not. However, neither clozapine nor haloperidol
      attenuated maintenance of chronic alcohol drinking. Taken together, the current
      data suggest that clozapine, but not haloperidol, may be effective at reducing
      alcohol abuse or non-dependent drinking and the P rat, used within an alcohol
      initiation paradigm, and may differentiate the effects of clozapine and
      haloperidol on alcohol drinking.

PMID- 24280364
TI  - [Acrokeratosis paraneoplastica of Bazex].

PMID- 24280365
TI  - Native efflux pumps contribute resistance to antimicrobials of skin and the
      ability of Staphylococcus aureus to colonize skin.
AB  - BACKGROUND:  Staphylococcus aureus colonizes skin in the presence of
      antimicrobial fatty acids and polyamines. The chromosomally encoded Tet38 efflux
      transporter confers resistance to tetracycline and fitness in abscesses, but its
      natural substrates and those of the Nor quinolone efflux pumps are unknown.
      METHODS:  Susceptibility of tet38 and other pump mutants to and pump gene
      induction by fatty acids and polyamines were compared. Transport of fatty acids
      by Tet38 was determined in membrane vesicles. Survival on skin was tested in an
      adapted mouse skin infection model. RESULTS:  The tet38 expression caused a 5- to
      8-fold increase in resistance to palmitoleic and undecanoic acids but not
      polyamines. Subinhibitory concentrations of these fatty acids induced 4-fold
      increases in tet38 transcripts and competitively inhibited transport of Hoechst
      33 342 dye in Tet38 membrane vesicles. Colonization of skin in BALB/c mice was
      decreased 5-fold in a Deltatet38 mutant, which was complemented by plasmid
      encoded tet38. Although polyamine minimum inhibitory concentrations (MICs)
      decreased 4-fold in a norC::cat mutant and increased 8-fold with norC
      overexpression, spermidine did not induce expression of norC and other pump
      genes, and norC::cat exhibited wild-type colonization. CONCLUSION:  Antibacterial
      fatty acids may be natural substrates of Tet38, which contributes to resistance
      and the ability of S. aureus to colonize skin.

PMID- 24280366
TI  - Increased incidence of urolithiasis and bacteremia during Proteus mirabilis and
      Providencia stuartii coinfection due to synergistic induction of urease activity.
AB  - BACKGROUND: Catheter-associated urinary tract infections (CaUTIs) are the most
      common hospital-acquired infections worldwide and are frequently polymicrobial.
      The urease-positive species Proteus mirabilis and Providencia stuartii are two of
      the leading causes of CaUTIs and commonly co-colonize catheters. These species
      can also cause urolithiasis and bacteremia. However, the impact of coinfection on
      these complications has never been addressed experimentally. METHODS: A mouse
      model of ascending UTI was utilized to determine the impact of coinfection on
      colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis
      or a urease mutant, P. stuartii, or a combination of these organisms. In vitro
      experiments were conducted to assess growth dynamics and impact of co-culture on
      urease activity. RESULTS: Coinfection resulted in a bacterial load similar to
      monospecies infection but with increased incidence of urolithiasis and
      bacteremia. These complications were urease-dependent as they were not observed
      during coinfection with a P. mirabilis urease mutant. Furthermore, total urease
      activity was increased during co-culture. CONCLUSIONS: We conclude that P.
      mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a
      urease-dependent manner, at least in part through synergistic induction of urease
      activity. These data provide a possible explanation for the high incidence of
      bacteremia resulting from polymicrobial CaUTI.

PMID- 24280367
TI  - Identifying potential therapeutic targets of methicillin-resistant Staphylococcus
      aureus through in vivo proteomic analysis.
AB  - BACKGROUND: Detailed knowledge on protein repertoire of a pathogen during host
      infection is needed for both developing a better understanding of the
      pathogenesis and defining potential therapeutic targets. Such data, however, have
      been missing for Staphylococcus aureus, a major human pathogen. METHODS: We
      determined the surface proteome of methicillin-resistant S. aureus (MRSA) clone
      usa300 derived directly from murine systemic infectiON. RESULTS: The majority of
      the in vivo-expressed surface-associated proteins were lipoproteins involved in
      nutrient acquisition, especially uptake of metal ions. Enzyme-linked
      immunosorbent assay (ELISA) of convalescent human serum samples revealed that
      proteins that were highly produced during murine experimental infection were also
      produced during natural human infection. We found that among the 7 highly
      abundant lipoproteins only MntC, which is the manganese-binding protein of the
      MntABC system, was essential for MRSA virulence during murine systemic infection.
      Moreover, we show that MntA and MntB are equally important for MRSA virulence.
      CONCLUSIONS: Besides providing experimental evidence that MntABC might be a
      potential therapeutic target for the development of antibiotics, our in vivo
      proteomics data will serve as a valuable basis for defining potential antigen
      combinations for multicomponent vaccines.

PMID- 24280368
TI  - Reply to Itzhaki and Klapper.

PMID- 24280369
TI  - Cytomegalovirus: an improbable cause of Alzheimer disease.

PMID- 24280370
TI  - The role of classical and alternative macrophages in the immunopathogenesis of
      herpes simplex virus-induced inflammation in a mouse model.
AB  - BACKGROUND: The exact mechanism of the inflammatory changes occurring during the
      development of Behcet's disease (BD) remains unclear. OBJECTIVE: We investigated
      the role of classical (M1) and alternative (M2) activation of macrophages in a
      herpes simplex virus (HSV)-induced BD mouse model. METHODS: The classical vs.
      alternative activated macrophage ratio (M1/M2 ratio) was calculated by analyzing
      the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow
      cytometry. mRNA expression of interferon (IFN)-gamma and interleukin (IL)-6 as M1
      and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse
      transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme
      linked immunosorbent assay. RESULTS: The M1 phenotype was upregulated in BD mice,
      and an increased M1/M2 ratio was observed compared to that in asymptomatic BD
      normal and normal healthy mice. Recombinant (r)IFN-gamma significantly increased
      the M1/M2 ratio (1.74+/-0.42) compared with that of rIL-4 (0.83+/-0.20). BD mice
      treated with rIL-4 showed a decreased M1/M2 ratio (1.2+/-0.3) compared to that of
      the rIFN-gamma- (2.1+/-2.3) treated group and also showed ameliorated BD symptoms
      accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4.
      CONCLUSION: Therefore, modulation of macrophage phenotypes could be an effective
      therapeutic approach for treating BD in the future.

PMID- 24280371
TI  - EI24 regulates epithelial-to-mesenchymal transition and tumor progression by
      suppressing TRAF2-mediated NF-kappaB activity.
AB  - Tumor metastasis is a multistep process that requires the concerted activity of
      discrete biological functions. The epithelial-to-mesenchymal transition (EMT) is
      the most critical mechanism implicated in tumor progression that is controlled by
      the inflammatory microenvironment. Understanding how an inflammatory
      microenvironment is maintained and contributes to tumor progression will be
      crucial for the development of new effective therapies. Here, we report that
      etoposide induced 2.4 (EI24) has a multifaceted role against tumor progression
      that is regulated by both EMT and inflammation. Decreased expression levels of
      EI24 in epithelial tumor cells induced EMT in association with increased cell
      motility and invasiveness and resistance to anoikis. Overexpression of EI24
      resulted in the opposite cell biological characteristics and suppressed in
      vivometastatic behavior. EI24 attenuated NF-kappaB activity by binding to the
      Complex I component TRAF2 and inducing its lysosome-dependent degradation,
      leading to transcriptional alterations of EMT- and inflammation-related genes.
      Analysis of clinical samples demonstrated that reduced EI24 expression and copy
      number was positively correlated with tumor malignancy and poor prognosis.
      Collectively, these findings establish EI24 as a critical suppressor of tumor
      progression and implicate EI24 expression level in malignant tumors as a useful
      therapeutic and diagnostic marker. 

PMID- 24280372
TI  - Evaluating HIV prevention efforts using semiparametric regression models: results
      from a large cohort of women participating in an HIV prevention trial from
      KwaZulu-Natal, South Africa.
AB  - OBJECTIVE: To describe and quantify the differences in risk behaviours, HIV
      prevalence and incidence rates by birth cohorts among a group of women in Durban,
      South Africa. METHODS: Cross-sectional and prospective cohort analyses were
      conducted for women who consented to be screened and enrolled in an HIV
      prevention trial. Demographic and sexual behaviours were described by five-year
      birth cohorts. Semiparametric regression models were used to investigate the
      bivariate associations between these factors and the birth cohorts. HIV
      seroconversion rates were also estimated by birth cohorts. RESULTS: The
      prevalence of HIV-1 infection at the screening visit was lowest (20.0%) among the
      oldest (born before 1960) cohorts, while the highest prevalence was observed
      among those born between 1975 and 79. Level of education increased across the
      birth cohorts while the median age at first sexual experience declined among
      those born after 1975 compared to those born before 1975. Only 33.03% of the
      oldest group reported ever using a condom while engaging in vaginal sex compared
      to 73.68% in the youngest group; however, HIV and other sexually transmitted
      infection (STI) incidence rates were significantly higher among younger women
      compared to older women. CONCLUSIONS: These findings clearly suggest that
      demographic and sexual risk behaviours are differentially related to the birth
      cohorts. Significantly high HIV and STI incidence rates were observed among the
      younger group. Although the level of education increased, early age at sexual
      debut was more common among the younger group. The continuing increase in HIV and
      STI incidence rates among the later cohorts suggests that the future trajectory
      of the epidemic will be dependent on the infection patterns in younger birth
      cohorts.

PMID- 24280373
TI  - Identifying childhood characteristics that underlie premorbid risk for substance
      use disorders: socialization and boldness.
AB  - We utilized a longitudinal twin study (N = 2,510) to identify the child
      characteristics present prior to initiation of substance use that best predicted
      later substance use disorders. Two independent traits accounted for the majority
      of premorbid risk: socialization (conformity to rules and conventional values)
      and boldness (sociability and social assurance, stress resilience, and thrill
      seeking). Low socialization was associated with disruptive behavior disorders,
      parental externalizing disorders, and environmental adversity and exhibited
      moderate genetic (0.45) and shared environmental influences (0.30). Boldness was
      highly heritable (0.71) and associated with less internalizing distress and
      environmental adversity. In combination, these traits exhibited robust
      associations with adolescent and young adult substance use disorders (R = .48 and
      .50, respectively) and incremental prediction over disruptive behavior disorders,
      parental externalizing disorders, and environmental adversity. The results were
      replicated in an independent sample. Socialization and boldness offer a novel
      conceptualization of underlying risk for substance use disorders that has the
      potential to improve prediction and theory with implications for basic research,
      prevention, and intervention. 

PMID- 24280374
TI  - Improvement of the Oryza sativa Nipponbare reference genome using next generation
      sequence and optical map data.
AB  - BACKGROUND: Rice research has been enabled by access to the high quality
      reference genome sequence generated in 2005 by the International Rice Genome
      Sequencing Project (IRGSP). To further facilitate genomic-enabled research, we
      have updated and validated the genome assembly and sequence for the Nipponbare
      cultivar of Oryza sativa (japonica group). RESULTS: The Nipponbare genome
      assembly was updated by revising and validating the minimal tiling path of clones
      with the optical map for rice. Sequencing errors in the revised genome assembly
      were identified by re-sequencing the genome of two different Nipponbare
      individuals using the Illumina Genome Analyzer II/IIx platform. A total of 4,886
      sequencing errors were identified in 321 Mb of the assembled genome indicating an
      error rate in the original IRGSP assembly of only 0.15 per 10,000 nucleotides. A
      small number (five) of insertions/deletions were identified using longer reads
      generated using the Roche 454 pyrosequencing platform. As the re-sequencing data
      were generated from two different individuals, we were able to identify a number
      of allelic differences between the original individual used in the IRGSP effort
      and the two individuals used in the re-sequencing effort. The revised assembly,
      termed Os-Nipponbare-Reference-IRGSP-1.0, is now being used in updated releases
      of the Rice Annotation Project and the Michigan State University Rice Genome
      Annotation Project, thereby providing a unified set of pseudomolecules for the
      rice community. CONCLUSIONS: A revised, error-corrected, and validated assembly
      of the Nipponbare cultivar of rice was generated using optical map data, re
      sequencing data, and manual curation that will facilitate on-going and future
      research in rice. Detection of polymorphisms between three different Nipponbare
      individuals highlights that allelic differences between individuals should be
      considered in diversity studies.

PMID- 24280375
TI  - Rice genes involved in phytosiderophore biosynthesis are synchronously regulated
      during the early stages of iron deficiency in roots.
AB  - BACKGROUND: The rice transcription factors IDEF1, IDEF2, and OsIRO2 have been
      identified as key regulators of the genes that control iron (Fe) uptake,
      including the biosynthesis of mugineic acid-family phytosiderophores (MAs). To
      clarify the onset of Fe deficiency, changes in gene expression were examined by
      microarray analysis using rice roots at 3, 6, 9, 12, 24, and 36 h after the onset
      of Fe-deficiency treatment. RESULTS: More than 1000 genes were found to be
      upregulated over a time course of 36 h. Expression of MAs-biosynthetic genes,
      OsIRO2, and the Fe3+-MAs complex transporter OsYSL15 was upregulated at the 24 h
      and 36 h time points. Moreover, these genes showed very similar patterns of
      expression changes, but their expression patterns were completely different from
      those of a metallothionein gene (OsIDS1) and the Fe2+-transporter genes OsIRT1
      and OsIRT2. OsIDS1 expression was upregulated by the 6 h time point. The early
      induction of OsIDS1 expression was distinct from the other Fe-deficiency
      inducible genes investigated and suggested a functional relationship with heavy
      metal homeostasis during the early stages of Fe deficiency. CONCLUSIONS: We
      showed that many genes related to MAs biosynthesis and transports were regulated
      by a distinct mechanism in roots. Furthermore, differences in expression changes
      and timing in response to Fe deficiency implied that different combinations of
      gene regulation mechanisms control the initial responses to Fe deficiency.

PMID- 24280376
TI  - Quantification of peramivir in dog plasma by liquid chromatography/tandem mass
      spectrometry employing precolumn derivatization.
AB  - Peramivir is a novel influenza neuraminidase inhibitor used for anti-influenza.
      In this article, a novel method was developed to determine peramivir in dog
      plasma using a derivatization treatment step to increase the retention time and
      enhance the signal intensity. The sample preparation consisted of a protein
      precipitation extraction followed by derivatization with 10M hydrochloric acid
      methanol (10:90, v/v) and determined by liquid chromatography coupled with tandem
      mass spectrometry. The selected reaction monitoring mode of the positive ion was
      performed and the precursor to the product ion transitions of m/z 343->284 and
      m/z 299->152 were used to measure the derivative of peramivir and Ro 64-0802
      (internal standard, an active metabolite of oseltamivir). The chromatographic
      separation was achieved using a ZORBAX RX-C8 (2.0mm*150mm*5MUm) analytical column
      with an isocratic mobile phase composed of acetonitrile-water-formic acid
      (30:70:0.1, v/v/v, 0.2mL/min). The method was linear over a concentration range
      of 0.25-250ng/mL. The average intra-day/inter-day precision values were 4.04
      8.17% and 3.02-7.08%, respectively, while the average accuracy value was 93.99
      106.48%. This method has been successfully applied to the preclinical dog
      research of peramivir following intragastric administration. 

PMID- 24280378
TI  - Androgen deprivation therapy and cardiovascular harm: are all men created equal?

PMID- 24280377
TI  - LKB1 is a central regulator of tumor initiation and pro-growth metabolism in
      ErbB2-mediated breast cancer.
AB  - BACKGROUND: Germline and somatic mutations in STK11, the gene encoding the
      serine/threonine kinase LKB1, are strongly associated with tumorigenesis. While
      loss of LKB1 expression has been linked to breast cancer, the mechanistic role of
      LKB1 in regulating breast cancer development, metastasis, and tumor metabolism
      has remained unclear. METHODS: We have generated and analyzed transgenic mice
      expressing ErbB2 in the mammary epithelium of LKB1 wild-type or LKB1-deficient
      mice. We have also utilized ErbB2-expressing breast cancer cells in which LKB1
      levels have been reduced using shRNA approaches. These transgenic and xenograft
      models were characterized for the effects of LKB1 loss on tumor initiation,
      growth, metastasis and tumor cell metabolism. RESULTS: We demonstrate that loss
      of LKB1 promotes tumor initiation and induces a characteristic shift to aerobic
      glycolysis ('Warburg effect') in a model of ErbB2-mediated breast cancer. LKB1
      deficient breast cancer cells display enhanced early tumor growth coupled with
      increased cell migratory and invasive properties in vitro. We show that ErbB2
      positive tumors deficient for LKB1 display a pro-growth molecular and phenotypic
      signature characterized by elevated Akt/mTOR signaling, increased glycolytic
      metabolism, as well as increased bioenergetic markers both in vitro and in vivo.
      We also demonstrate that mTOR contributes to the metabolic reprogramming of LKB1
      deficient breast cancer, and is required to drive glycolytic metabolism in these
      tumors; however, LKB1-deficient breast cancer cells display reduced metabolic
      flexibility and increased apoptosis in response to metabolic perturbations.
      CONCLUSIONS: Together, our data suggest that LKB1 functions as a tumor suppressor
      in breast cancer. Loss of LKB1 collaborates with activated ErbB2 signaling to
      drive breast tumorigenesis and pro-growth metabolism in the resulting tumors.

PMID- 24280379
TI  - Fumonisin B1 induces global DNA hypomethylation in HepG2 cells - An alternative
      mechanism of action.
AB  - Fumonisin B1 (FB1), a common mycotoxin contaminant of maize, is known to inhibit
      sphingolipid biosynthesis and has been implicated in cancer promoting activity in
      animals and humans. FB1 disrupts DNA methylation and chromatin modifications in
      human hepatoma (HepG2) cells. We investigated the effect of FB1 on enzymes, DNA
      methyltransferases and demethylases, involved in chromatin maintenance and gross
      changes in structural integrity of DNA in HepG2 cells. We measured: (i) the
      expression of 84 key genes encoding enzymes known to modify genomic DNA and
      histones (superarray and qPCR); (ii) protein expression of DNA methyltransferases
      (DNMT1, DNMT3A and DNMT3B) and the major demethylase (MBD2) (western blotting);
      (iii) degree of DNA methylation by FACS using anti-5-MeCyt and (iv) DNA migration
      (single cell gel electrophoresis). FB1 significantly decreased the
      methyltransferase activities of DNMT1, DNMT3A and DNMT3B, and significantly up
      regulated the demethylases (MBD2 expression and activity, and KDM5B and KDM5C
      expression). FACS data showed FB1 significantly increased DNA hypomethylation and
      resulted in gross changes in structural DNA as evidenced by the Comet assay. We
      conclude that FB1 induces global DNA hypomethylation and histone demethylation
      that causes chromatin instability and may lead to liver tumourigenesis.

PMID- 24280380
TI  - Single high-dose dexamethasone and sodium salicylate failed to attenuate phosgene
      induced acute lung injury in rats.
AB  - Life-threatening acute lung injury potentially occurs following high-level
      accidental exposures to phosgene gas. This situation was mirrored in rats exposed
      nose-only at 900-1000 mg phosgene/m(3)min. At this exposure level, previous
      studies on rats demonstrated sustained reflexively induced cardiopulmonary
      dysfunction and evidence of vascular fluid redistribution. These findings
      challenge the currently applied treatment strategies to mitigate the presumed non
      cardiogenic lung edema by steroidal or non-steroidal anti-inflammatory drugs.
      This study investigates whether high doses of curatively administered
      dexamethasone (DX; 100 mg/kg bw, ip) and sodium salicylate (SS; 200 mg/kg bw,
      ip), alone or in combination, show efficacy to mitigate the phosgene-induced lung
      edema. Exhaled nitric oxide (eNO), animal morbidity and mortality, and increased
      lung weights one day postexposure served as endpoints of lung injury and drug
      efficacy. When applying this dosing regimen, SS showed minimal (if any) efficacy
      while DX, alone or in combination with SS, substantially aggravated the emerging
      lung edema (lung weights) with 40% mortality. The degree of acute lung injury
      (ALI) was mirrored by increased eNO. Its direct relationship to ALI-severity was
      evidenced by decreased eNO following NO-synthetase inhibitor administration
      (aminoguanidine-aerosol) and associated mitigation of ALI. All non-treated
      phosgene-exposed as well as treated but non-phosgene-exposed rats survived. This
      experimental evidence suggests that high-dose corticoid treatments may aggravate
      the pulmonary toxicity of phosgene. Similarly, this outcome supports the
      supposition that non-inflammatory, cardiogenic and/or neurogenic factors play a
      role in this type of acute lung injury.

PMID- 24280381
TI  - Respiratory toxicity of repeated exposure to particles produced by traffic and
      sugar cane burning.
AB  - We compared the toxicity of subchronic exposure to equivalent masses of particles
      from sugar cane burning and traffic. BALB/c mice received 3 intranasal
      instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4)
      or particles (15MUg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2,
      BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the
      last instillation. In all instances UP and BP groups presented worse pulmonary
      elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction
      and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented
      more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse
      bronchial and alveolar lesion scores than their controls; BP4 had greater
      bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4.
      In conclusion, biomass particles were more toxic than those from traffic after
      repeated exposures. 

PMID- 24280382
TI  - Effect of rostral fluid shift on pharyngeal resistance in men with and without
      obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) relates to overnight rostral fluid
      shift, possibly because fluid accumulation around the pharynx increases
      pharyngeal resistance (Rph). We hypothesised that Rph will increase more in men
      with than without OSA in response to rostral fluid redistribution. METHODS:
      Seventeen men with, and 12 without OSA were randomized to lower body positive
      pressure (LBPP) for 15min or control, then crossed over. Leg fluid volume (LFV)
      and Rph were measured before and after each period. RESULTS: LBPP displaced
      similar amounts of fluid from the legs in both groups. However, compared to the
      non-OSA group, Rph increased significantly more during LBPP in the OSA group (
      0.38+/-2.87 vs. 2.52+/-2.94cmH2O/l/s, p=0.016). Change in Rph during LBPP
      correlated directly with baseline Rph in the OSA group, but inversely in the non
      OSA group. CONCLUSION: OSA patients have increased susceptibility to pharyngeal
      obstruction in response to rostral fluid redistribution, which could predispose
      to pharyngeal collapse during sleep.

PMID- 24280383
TI  - Higher risk of mood disorders among adolescents with ADHD and asthma: a
      nationwide prospective study.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and asthma are
      commonly comorbid together, and are associated with an increased risk of
      development of mood disorders separately. However, there has been no study
      investigating the comorbid effect of these two disorders on developing mood
      disorder. METHODS: Using the National Health Insurance Research Database,
      adolescents with ADHD-alone, asthma-alone, ADHD comorbid with asthma, and age
      /gender-matched (1:4) controls were recruited in 2003. Subjects who developed
      major depression, any depressive disorder, or bipolar disorder during the follow
      up period (2003-2010) were identified. RESULTS: In all, 1172 adolescents with
      ADHD-alone, 487 with asthma-alone, 238 with ADHD+asthma, and 7552 controls were
      recruited in 2003. Adolescents with ADHD+asthma and those with ADHD-alone, but
      not those with asthma-alone, had an elevated risk of developing major depression
      (hazard ratio [HR]: 10.25, 95% confidence interval [CI]: 3.86-27.19; HR: 8.64,
      95%CI: 5.00-14.93; HR: 2.11, 95%CI: 0.71-6.23) and bipolar disorder (HR: 31.25,
      95%CI: 8.87-110.12; HR: 10.42, 95%CI: 4.60-23.63; HR: 1.91, 95%CI: 0.24-15.32)
      compared to the control group. DISCUSSION: Our results showed that ADHD
      adolescents had an increased risk of developing both unipolar depression and
      bipolar depression in their later life, and that the comorbidity of asthma with a
      synergistic effect increased this risk further. The underlying pathophysiology
      among ADHD, asthma, and mood disorders needs further investigation.

PMID- 24280384
TI  - Pollen tube growth regulation by free anions depends on the interaction between
      the anion channel SLAH3 and calcium-dependent protein kinases CPK2 and CPK20.
AB  - Apical growth in pollen tubes (PTs) is associated with the presence of tip
      focused ion gradients and fluxes, implying polar localization or regulation of
      the underlying transporters. The molecular identity and regulation of anion
      transporters in PTs is unknown. Here we report a negative gradient of cytosolic
      anion concentration focused on the tip, in negative correlation with the
      cytosolic Ca(2+) concentration. We hypothesized that a possible link between
      these two ions is based on the presence of Ca(2+)-dependent protein kinases
      (CPKs). We characterized anion channels and CPK transcripts in PTs and analyzed
      their localization. Yellow fluorescent protein (YFP) tagging of a homolog of SLOW
      ANION CHANNEL-ASSOCIATED1 (SLAH3:YFP) was widespread along PTs, but, in
      accordance with the anion efflux, CPK2/CPK20/CPK17/CPK34:YFP fluorescence was
      strictly localized at the tip plasma membrane. Expression of SLAH3 with either
      CPK2 or CPK20 (but not CPK17/CPK34) in Xenopus laevis oocytes elicited S-type
      anion channel currents. Interaction of SLAH3 with CPK2/CPK20 (but not
      CPK17/CPK34) was confirmed by Forster-resonance energy transfer fluorescence
      lifetime microscopy in Arabidopsis thaliana mesophyll protoplasts and bimolecular
      fluorescence complementation in living PTs. Compared with wild-type PTs, slah3-1
      and slah3-2 as well as cpk2-1 cpk20-2 PTs had reduced anion currents. Double
      mutant cpk2-1 cpk20-2 and slah3-1 PTs had reduced extracellular anion fluxes at
      the tip. Our studies provide evidence for a Ca(2+)-dependent CPK2/CPK20
      regulation of the anion channel SLAH3 to regulate PT growth.

PMID- 24280385
TI  - Endoplasmic reticulum glucosidases and protein quality control factors cooperate
      to establish biotrophy in Ustilago maydis.
AB  - Secreted fungal effectors mediate plant-fungus pathogenic interactions. These
      proteins are typically N-glycosylated, a common posttranslational modification
      affecting their location and function. N-glycosylation consists of the addition,
      and subsequent maturation, of an oligosaccharide core in the endoplasmic
      reticulum (ER) and Golgi apparatus. In this article, we show that two enzymes
      catalyzing specific stages of this pathway in maize smut (Ustilago maydis),
      glucosidase I (Gls1) and glucosidase II beta-subunit (Gas2), are essential for
      its pathogenic interaction with maize (Zea mays). Gls1 is required for the
      initial stages of infection following appressorium penetration, and Gas2 is
      required for efficient fungal spreading inside infected tissues. While U. maydis
      Deltagls1 cells induce strong plant defense responses, Deltagas2 hyphae are able
      to repress them, showing that slight differences in the N-glycoprotein processing
      can determine the extent of plant-fungus interactions. Interestingly, the
      calnexin protein, a central element of the ER quality control system for N
      glycoproteins in eukaryotic cells, is essential for avoiding plant defense
      responses in cells with defective N-glycoproteins processing. Thus, N
      glycoprotein maturation and this conserved checkpoint appear to play an important
      role in the establishment of an initial biotrophic state with the plant, which
      allows subsequent colonization.

PMID- 24280386
TI  - The actin-related Protein2/3 complex regulates mitochondrial-associated calcium
      signaling during salt stress in Arabidopsis.
AB  - Microfilament and Ca(2+) dynamics play important roles in stress signaling in
      plants. Through genetic screening of Arabidopsis thaliana mutants that are
      defective in stress-induced increases in cytosolic Ca(2+) ([Ca(2+)]cyt), we
      identified Actin-Related Protein2 (Arp2) as a regulator of [Ca(2+)]cyt in
      response to salt stress. Plants lacking Arp2 or other proteins in the Arp2/3
      complex exhibited enhanced salt-induced increases in [Ca(2+)]cyt, decreased
      mitochondria movement, and hypersensitivity to salt. In addition, mitochondria
      aggregated, the mitochondrial permeability transition pore opened, and
      mitochondrial membrane potential Psim was impaired in the arp2 mutant, and these
      changes were associated with salt-induced cell death. When opening of the
      enhanced mitochondrial permeability transition pore was blocked or increases in
      [Ca(2+)]cyt were prevented, the salt-sensitive phenotype of the arp2 mutant was
      partially rescued. These results indicate that the Arp2/3 complex regulates
      mitochondrial-dependent Ca(2+) signaling in response to salt stress.

PMID- 24280387
TI  - Jumonji C domain protein JMJ705-mediated removal of histone H3 lysine 27
      trimethylation is involved in defense-related gene activation in rice.
AB  - Histone methylation is an important epigenetic modification in chromatin
      function, genome activity, and gene regulation. Dimethylated or trimethylated
      histone H3 lysine 27 (H3K27me2/3) marks silent or repressed genes involved in
      developmental processes and stress responses in plants. However, the role and the
      mechanism of the dynamic removal of H3K27me2/3 during gene activation remain
      unclear. Here, we show that the rice (Oryza sativa) Jumonji C (jmjC) protein gene
      JMJ705 encodes a histone lysine demethylase that specifically reverses
      H3K27me2/3. The expression of JMJ705 is induced by stress signals and during
      pathogen infection. Overexpression of the gene reduces the resting level of
      H3K27me2/3 resulting in preferential activation of H3K27me3-marked biotic stress
      responsive genes and enhances rice resistance to the bacterial blight disease
      pathogen Xanthomonas oryzae pathovar oryzae. Mutation of the gene reduces plant
      resistance to the pathogen. Further analysis revealed that JMJ705 is involved in
      methyl jasmonate-induced dynamic removal of H3K27me3 and gene activation. The
      results suggest that JMJ705 is a biotic stress-responsive H3K27me2/3 demethylase
      that may remove H3K27me3 from marked defense-related genes and increase their
      basal and induced expression during pathogen infection.

PMID- 24280388
TI  - MAIGO5 functions in protein export from Golgi-associated endoplasmic reticulum
      exit sites in Arabidopsis.
AB  - Plant cells face unique challenges to efficiently export cargo from the
      endoplasmic reticulum (ER) to mobile Golgi stacks. Coat protein complex II
      (COPII) components, which include two heterodimers of Secretory23/24 (Sec23/24)
      and Sec13/31, facilitate selective cargo export from the ER; however, little is
      known about the mechanisms that regulate their recruitment to the ER membrane,
      especially in plants. Here, we report a protein transport mutant of Arabidopsis
      thaliana, named maigo5 (mag5), which abnormally accumulates precursor forms of
      storage proteins in seeds. mag5-1 has a deletion in the putative ortholog of the
      Saccharomyces cerevisiae and Homo sapiens Sec16, which encodes a critical
      component of ER exit sites (ERESs). mag mutants developed abnormal structures
      (MAG bodies) within the ER and exhibited compromised ER export. A functional
      MAG5/SEC16A-green fluorescent protein fusion localized at Golgi-associated cup
      shaped ERESs and cycled on and off these sites at a slower rate than the COPII
      coat. MAG5/SEC16A interacted with SEC13 and SEC31; however, in the absence of
      MAG5/SEC16A, recruitment of the COPII coat to ERESs was accelerated. Our results
      identify a key component of ER export in plants by demonstrating that MAG5/SEC16A
      is required for protein export at ERESs that are associated with mobile Golgi
      stacks, where it regulates COPII coat turnover.

PMID- 24280392
TI  - How far to the road not taken? The effect of psychological distance on
      counterfactual direction.
AB  - Upward and downward counterfactuals serve the distinct motivational functions of
      self-improvement and self-enhancement, respectively. Drawing on construal level
      theory, which contends that increasing psychological distance from an event leads
      people to focus on high-level, self-improvement versus low-level, self
      enhancement goals, we propose that distance will alter counterfactual direction
      in a way that satisfies these distinct motives. We found that people generated
      more downward counterfactuals about recent versus distant past events, while they
      tended to generate more upward counterfactuals about distant versus recent past
      events (Experiment 1). Consistent results were obtained for social distance
      (Experiment 2). Experiment 3 demonstrated that distance affects the direction of
      open-ended counterfactual thoughts. Finally, Experiment 4 explored a potential
      mechanism, demonstrating that manipulating temporal distance produced changes in
      participants' self-improvement versus self-enhancement motivations when
      responding to negative events. Future directions and broader implications for
      self-control, social support, empathy, and learning are discussed. 

PMID- 24280393
TI  - Can the formation of conditioned attitudes be intentionally controlled?
AB  - Evaluative conditioning (EC) is defined as the change in the evaluation of a
      conditioned stimulus (CS) due to its pairing with a valenced unconditioned
      stimulus (US). Counter to views that EC is the product of automatic learning
      processes, recent research has revealed various characteristics of nonautomatic
      processing in EC. The current research investigated whether the formation of
      conditioned attitudes can be intentionally controlled. Whereas EC effects on self
      reported evaluations were reduced (enhanced) when participants were instructed to
      prevent (promote) the influence of CS-US pairings, EC effects on an evaluative
      priming measure remained unaffected by control instructions. Moreover, although
      EC effects on self-reported evaluations varied as a function of evaluative
      priming effects and recollective memory for CS-US pairings, motivation to control
      the influence of CS-US pairings qualified only the predictive relation of
      recollective memory. The results highlight functionally distinct contributions of
      uncontrollable encoding-related processes and controllable expression-related
      processes to EC effects. 

PMID- 24280391
TI  - Rho of plant GTPase signaling regulates the behavior of Arabidopsis kinesin-13A
      to establish secondary cell wall patterns.
AB  - Plant cortical microtubule arrays determine the cell wall deposition pattern and
      proper cell shape and function. Although various microtubule-associated proteins
      regulate the cortical microtubule array, the mechanisms underlying marked
      rearrangement of cortical microtubules during xylem differentiation are not fully
      understood. Here, we show that local Rho of Plant (ROP) GTPase signaling targets
      an Arabidopsis thaliana kinesin-13 protein, Kinesin-13A, to cortical microtubules
      to establish distinct patterns of secondary cell wall formation in xylem cells.
      Kinesin-13A was preferentially localized with cortical microtubules in secondary
      cell wall pits, areas where cortical microtubules are depolymerized to prevent
      cell wall deposition. This localization of Kinesin-13A required the presence of
      the activated ROP GTPase, MICROTUBULE DEPLETION DOMAIN1 (MIDD1) protein, and
      cortical microtubules. Knockdown of Kinesin-13A resulted in the formation of
      smaller secondary wall pits, while overexpression of Kinesin-13A enlarged their
      surface area. Kinesin-13A alone could depolymerize microtubules in vitro;
      however, both MIDD1 and Kinesin-13A were required for the depolymerization of
      cortical microtubules in vivo. These results indicate that Kinesin-13A regulates
      the formation of secondary wall pits by promoting cortical microtubule
      depolymerization via the ROP-MIDD1 pathway.

PMID- 24280390
TI  - SND1 transcription factor-directed quantitative functional hierarchical genetic
      regulatory network in wood formation in Populus trichocarpa.
AB  - Wood is an essential renewable raw material for industrial products and energy.
      However, knowledge of the genetic regulation of wood formation is limited. We
      developed a genome-wide high-throughput system for the discovery and validation
      of specific transcription factor (TF)-directed hierarchical gene regulatory
      networks (hGRNs) in wood formation. This system depends on a new robust procedure
      for isolation and transfection of Populus trichocarpa stem differentiating xylem
      protoplasts. We overexpressed Secondary Wall-Associated NAC Domain 1s (Ptr-SND1
      B1), a TF gene affecting wood formation, in these protoplasts and identified
      differentially expressed genes by RNA sequencing. Direct Ptr-SND1-B1-DNA
      interactions were then inferred by integration of time-course RNA sequencing data
      and top-down Graphical Gaussian Modeling-based algorithms. These Ptr-SND1-B1-DNA
      interactions were verified to function in differentiating xylem by anti-PtrSND1
      B1 antibody-based chromatin immunoprecipitation (97% accuracy) and in stable
      transgenic P. trichocarpa (90% accuracy). In this way, we established a Ptr-SND1
      B1-directed quantitative hGRN involving 76 direct targets, including eight TF and
      61 enzyme-coding genes previously unidentified as targets. The network can be
      extended to the third layer from the second-layer TFs by computation or by
      overexpression of a second-layer TF to identify a new group of direct targets
      (third layer). This approach would allow the sequential establishment, one two
      layered hGRN at a time, of all layers involved in a more comprehensive hGRN. Our
      approach may be particularly useful to study hGRNs in complex processes in plant
      species resistant to stable genetic transformation and where mutants are
      unavailable.

PMID- 24280394
TI  - Circumplex Scales of Intergroup Goals: an interpersonal circle model of goals for
      interactions between groups.
AB  - Six studies (N = 1,682) used the Circumplex Scales of Intergroup Goals (CSIG)--an
      inventory based on the interpersonal circle-to assess individuals' agentic and
      communal goals for interactions between groups (nations in Studies 1-4,
      organizations in Study 5, political parties in Study 6). Noteworthy findings
      included the following: People with stronger unagentic-and-uncommunal goals
      perceived other groups as dangers, were wary of intergroup negotiations, and
      sanctioned authoritarianism and inequality. People with stronger agentic-and
      uncommunal goals proudly identified with their country and compatriots,
      disapproved of nations unlike their own, and preferred the conservative candidate
      in a national election. People with stronger communal-and-unagentic goals
      identified with people beyond their ingroup, and wanted their group to resolve
      intergroup conflicts by behaving cooperatively rather than competitively or
      aggressively. By providing an encompassing framework capable of organizing and
      integrating these types of diverse findings, the circumplex model can facilitate
      cumulative scientific progress.

PMID- 24280395
TI  - Anorectal anatomy and imaging techniques.
AB  - The rectum and anus are two anatomically complex organs with diverse pathologies.
      This article reviews the basic anatomy of the rectum and anus. In addition, it
      addresses the current radiographic techniques used to evaluate these structures,
      specifically ultrasound, magnetic resonance imaging, and defecography. 

PMID- 24280396
TI  - Anorectal physiology and testing.
AB  - A good understanding of anorectal physiology is essential for the diagnosis and
      appropriate treatment of various anorectal disorders, such as fecal incontinence,
      constipation, and pain. This article reviews the physiology of the anorectum and
      details the various investigations used to diagnose anorectal physiology
      disorders. These anatomic and functional tests include anal manometry, endoanal
      ultrasound, defecography, balloon expulsion test, magnetic resonance imaging,
      pudendal nerve terminal motor latency, electromyography, and colonic transit
      studies. Indications for investigations, steps in performing the tests, and
      interpretation of results are discussed. 

PMID- 24280397
TI  - Anal fissure and stenosis.
AB  - Anal fissure is a common anorectal disorder resulting in anal pain and bleeding.
      Fissures can either heal spontaneously and be classified as acute, or persist for
      6 or more weeks and be classified as chronic, ultimately necessitating treatment.
      Anal stenosis is a challenging problem most commonly resulting from trauma, such
      as excisional hemorrhoidectomy. This frustrating issue for the patient is equally
      as challenging to the surgeon. This article reviews these 2 anorectal disorders,
      covering their etiology, mechanism of disease, diagnosis, and algorithm of
      management. 

PMID- 24280398
TI  - Modern management of hemorrhoidal disease.
AB  - Complaints secondary to hemorrhoidal disease have been treated by health care
      providers for centuries. Most symptoms referable to hemorrhoidal disease can be
      managed nonoperatively. When symptoms do not respond to medical therapy,
      procedural intervention is recommended. Surgical hemorrhoidectomy is usually
      reserved for patients who are refractory to or unable to tolerate office
      procedures. This article reviews the pathophysiology of hemorrhoidal disease and
      the most commonly used techniques for the nonoperative and operative palliation
      of hemorrhoidal complaints. 

PMID- 24280399
TI  - Anal abscess and fistula.
AB  - Benign anorectal diseases, such as anal abscesses and fistula, are commonly seen
      by primary care physicians, gastroenterologists, emergency physicians, general
      surgeons, and colorectal surgeons. It is important to have a thorough
      understanding of the complexity of these 2 disease processes so as to provide
      appropriate and timely treatment. We review the pathophysiology, presentation,
      diagnosis, and treatment options for both anal abscesses and fistulas. 

PMID- 24280389
TI  - Systems-level analysis of nitrogen starvation-induced modifications of carbon
      metabolism in a Chlamydomonas reinhardtii starchless mutant.
AB  - To understand the molecular basis underlying increased triacylglycerol (TAG)
      accumulation in starchless (sta) Chlamydomonas reinhardtii mutants, we undertook
      comparative time-course transcriptomics of strains CC-4348 (sta6 mutant), CC
      4349, a cell wall-deficient (cw) strain purported to represent the parental STA6
      strain, and three independent STA6 strains generated by complementation of sta6
      (CC-4565/STA6-C2, CC-4566/STA6-C4, and CC-4567/STA6-C6) in the context of N
      deprivation. Despite N starvation-induced dramatic remodeling of the
      transcriptome, there were relatively few differences (5 * 10(2)) observed between
      sta6 and STA6, the most dramatic of which were increased abundance of transcripts
      encoding key regulated or rate-limiting steps in central carbon metabolism,
      specifically isocitrate lyase, malate synthase, transaldolase, fructose
      bisphosphatase and phosphoenolpyruvate carboxykinase (encoded by ICL1, MAS1,
      TAL1, FBP1, and PCK1 respectively), suggestive of increased carbon movement
      toward hexose-phosphate in sta6 by upregulation of the glyoxylate pathway and
      gluconeogenesis. Enzyme assays validated the increase in isocitrate lyase and
      malate synthase activities. Targeted metabolite analysis indicated increased
      succinate, malate, and Glc-6-P and decreased Fru-1,6-bisphosphate, illustrating
      the effect of these changes. Comparisons of independent data sets in multiple
      strains allowed the delineation of a sequence of events in the global N
      starvation response in C. reinhardtii, starting within minutes with the
      upregulation of alternative N assimilation routes and carbohydrate synthesis and
      subsequently a more gradual upregulation of genes encoding enzymes of TAG
      synthesis. Finally, genome resequencing analysis indicated that (1) the deletion
      in sta6 extends into the neighboring gene encoding respiratory burst oxidase, and
      (2) a commonly used STA6 strain (CC-4349) as well as the sequenced reference (CC
      503) are not congenic with respect to sta6 (CC-4348), underscoring the importance
      of using complemented strains for more rigorous assignment of phenotype to
      genotype.

PMID- 24280400
TI  - Chronic pelvic pain.
AB  - Chronic pelvic pain is pain lasting longer than 6 months and is estimated to
      occur in 15% of women. Causes of pelvic pain include disorders of gynecologic,
      urologic, gastroenterologic, and musculoskeletal systems. The multidisciplinary
      nature of chronic pelvic pain may complicate diagnosis and treatment. Treatments
      vary by cause but may include medicinal, neuroablative, and surgical treatments.

PMID- 24280401
TI  - Pruritus ani: diagnosis and treatment.
AB  - Pruritus ani is a common condition with multiple causes. Primary causes are
      thought to be fecal soiling or food irritants. Secondary causes include
      malignancy, infections including sexually transmitted diseases, benign anorectal
      diseases, systemic diseases, and inflammatory conditions. A broad differential
      diagnosis must be considered. A reassessment of the diagnosis is required if
      symptoms or findings are not responsive to therapy. The pathophysiology of
      itching, an overview of primary and secondary causes, and various treatment
      options are reviewed. 

PMID- 24280402
TI  - Surgical management of fecal incontinence.
AB  - The surgical approach to treating fecal incontinence is complex. After optimal
      medical management has failed, surgery remains the best option for restoring
      function. Patient factors, such as prior surgery, anatomic derangements, and
      degree of incontinence, help inform the astute surgeon regarding the most
      appropriate option. Many varied approaches to surgical management are available,
      ranging from more conservative approaches, such as anal canal bulking agents and
      neuromodulation, to more aggressive approaches, including sphincter repair, anal
      cerclage techniques, and muscle transposition. Efficacy and morbidity of these
      approaches also range widely, and this article presents the data and operative
      considerations for these approaches. 

PMID- 24280403
TI  - Rectal prolapse and intussusception.
AB  - Rectal prolapse continues to be problematic for both patients and surgeons alike,
      in part because of increased recurrence rates despite several well-described
      operations. Patients should be aware that although the prolapse will resolve with
      operative therapy, functional results may continue to be problematic. This
      article describes the recommended evaluation, role of adjunctive testing, and
      outcomes associated with both perineal and abdominal approaches. 

PMID- 24280404
TI  - Constipation and pelvic outlet obstruction.
AB  - Caring for patients with constipation and pelvic outlet obstruction can be
      challenging, requiring skill, patience, and empathy on the part of the medical
      professional. The mainstay of treatment is behavioral with surgery reserved for a
      select group of patients. The evaluation, diagnostic, and treatment modalities of
      both constipation and pelvic outlet with a focus on current advancements and
      technology are explored in depth. 

PMID- 24280405
TI  - Sexually transmitted and anorectal infectious diseases.
AB  - Sexually transmitted diseases (STDs) are common and they can involve the anus and
      rectum in both men and women. In this article, the main bacterial and viral STDs
      that affect the anus and rectum are discussed, including their prevalence,
      presentation, and treatment. 

PMID- 24280406
TI  - Anal squamous intraepithelial neoplasia.
AB  - Diagnosis, follow up, and treatment of anal intraepithelial neoplasia are complex
      and not standardized. This may be partly caused by poor communication of biopsy
      and cytology findings between pathologists and clinicians as a result of a
      disparate and confusing terminology used to classify these lesions. This article
      focuses on general aspects of epidemiology and on clarifying the current
      terminology of intraepithelial squamous neoplasia, its relationship with human
      papilloma virus infection, and the current methods that exist to diagnose and
      treat this condition. 

PMID- 24280407
TI  - Management of radiation proctitis.
AB  - Radiation damage to the rectum following radiotherapy for pelvic malignancies can
      range from acute dose-limiting side effects to major morbidity affecting health
      related quality of life. No standard guidelines exist for diagnosis and
      management of radiation proctitis. This article reviews the definitions, staging,
      and clinical features of radiation proctitis, and summarizes the modalities
      available for the treatment of acute and chronic radiation proctitis. Because of
      the paucity of well-controlled, blinded, randomized studies, it is not possible
      to fully assess the comparative efficacy of the different approaches to
      management. However, the evidence and rationale for use of the different
      strategies are presented. 

PMID- 24280408
TI  - Disorders of the anorectum and pelvic floor.

PMID- 24280411
TI  - In situ mutation detection and visualization of intratumor heterogeneity for
      cancer research and diagnostics.
AB  - Current assays for somatic mutation analysis are based on extracts from tissue
      sections that often contain morphologically heterogeneous neoplastic regions with
      variable contents of normal stromal and inflammatory cells, obscuring the results
      of the assays. We have developed an RNA-based in situ mutation assay that targets
      oncogenic mutations in a multiplex fashion that resolves the heterogeneity of the
      tissue sample. Activating oncogenic mutations are targets for a new generation of
      cancer drugs. For anti-EGFR therapy prediction, we demonstrate reliable in situ
      detection of KRAS mutations in codon 12 and 13 in colon and lung cancers in three
      different types of routinely processed tissue materials. High-throughput
      screening of KRAS mutation status was successfully performed on a tissue
      microarray. Moreover, we show how the patterns of expressed mutated and wild-type
      alleles can be studied in situ in tumors with complex combinations of mutated
      EGFR, KRAS and TP53. This in situ method holds great promise as a tool to
      investigate the role of somatic mutations during tumor progression and for
      prediction of response to targeted therapy. 

PMID- 24280412
TI  - Studies on the codling moth (Lepidoptera: Tortricidae) response to different
      codlemone release rates.
AB  - The response of the codling moth (Cydia pomonella L. (Lepidoptera: Tortricidae))
      to different emission values of its main pheromone component, 8E,10E-dodecadien-1
      ol (codlemone), was investigated in three field trials conducted in plots without
      mating disruption treatments. Moth catches obtained in traps baited with
      pheromone dispensers were correlated with the corresponding codlemone release
      rates by multiple regression analysis. In a preliminary trial conducted in Lleida
      (NE Spain), a decreasing trend of captures was observed based on increasing
      pheromone levels. After this, the pheromone release profiles of the pheromone
      dispensers were studied, in parallel with the field trials, by residual codlemone
      extraction and gas chromatography quantification. In the trials carried out in
      Asturias (NW Spain), a correlation between trap catches and emission levels
      (within the range from 11 to 1,078 MUg/d) was found and fitted a logarithmic
      model. Captures followed a decreasing linear trend in the range of emission rates
      from 11 to 134 MUg/d. Given that release values comprised between 11 and 67 MUg/d
      did not lead to significantly different catches in traps, this emission range
      could be considered to develop effective formulations for attraction purposes
      when mating disruption is not acting in the environment. 

PMID- 24280413
TI  - Retraction notice.

PMID- 24280414
TI  - Erratum.

PMID- 24280416
TI  - Mothers' depressive symptoms and infant negative emotionality in the prediction
      of child adjustment at age 3: testing the maternal reactivity and child
      vulnerability hypotheses.
AB  - This study examined individual differences in how mothers' depressive symptoms
      affect children's early adjustment. It tested whether problematic development
      among children high in negative emotionality is accentuated by (a) maternal
      reactivity, the negative reactivity of mothers with depressive symptoms to
      difficult child characteristics; and (b) child vulnerability, the susceptibility
      of negatively emotional children to the negative parenting of mothers with
      depressive symptoms. Based on 1,364 participants from the NICHD Study of Early
      Child Care, results showed that mothers' depressive symptoms predicted greater
      risk for adjustment problems at age 3 among children who as infants were high
      rather than low in negative emotionality. Increased risk was evident for behavior
      problems, low responsiveness, high separation distress, and low social
      competence. Mediational tests suggested that increased risk reflected maternal
      reactivity: the stronger mothers' depressive symptoms, the more they responded
      with negative parenting to children high in negative emotionality. The proposal
      that child vulnerability mediates the greater impact of mothers' depressive
      symptoms on negatively emotional children was verified only for separation
      distress. The results support the proposal that, when mothers are high in
      depressive symptoms, aversive characteristics of children and their behavior
      increasingly influence early adjustment and do so because they elicit negative
      parent behavior. 

PMID- 24280415
TI  - CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced
      hepatic steatosis.
AB  - CD36 is a scavenger receptor with multiple ligands and cellular functions,
      including facilitating cellular uptake of free fatty acids (FFAs). Chronic
      alcohol consumption increases hepatic CD36 expression, leading to the hypothesis
      that this promotes uptake of circulating FFAs, which then serve as a substrate
      for triglyceride (TG) synthesis and the development of alcoholic steatosis. We
      investigated this hypothesis in alcohol-fed wild-type and Cd36-deficient (Cd36(-/
      )) mice using low-fat/high-carbohydrate Lieber-DeCarli liquid diets, positing
      that Cd36(-/-) mice would be resistant to alcoholic steatosis. Our data show that
      the livers of Cd36(-/-) mice are resistant to the lipogenic effect of consuming
      high-carbohydrate liquid diets. These mice also do not further develop alcoholic
      steatosis when chronically fed alcohol. Surprisingly, we did not detect an effect
      of alcohol or CD36 deficiency on hepatic FFA uptake; however, the lower baseline
      levels of hepatic TG in Cd36(-/-) mice fed a liquid diet were associated with
      decreased expression of genes in the de novo lipogenesis pathway and a lower rate
      of hepatic de novo lipogenesis. In conclusion, Cd36(-/-) mice are resistant to
      hepatic steatosis when fed a high-carbohydrate liquid diet, and they are also
      resistant to alcoholic steatosis. These studies highlight an important role for
      CD36 in hepatic lipid homeostasis that is not associated with hepatic fatty acid
      uptake. 

PMID- 24280417
TI  - Development of breeding lines with three pyramided resistance genes that confer
      broad-spectrum bacterial blight resistance and their molecular analysis in rice.
AB  - BACKGROUND: The development of resistant cultivars has been the most effective
      and economical strategy to control bacterial leaf blight (BB) disease of rice
      caused by Xanthomonas oryzae pv. oryzae (Xoo). Molecular markers have made it
      possible to identify and pyramid valuable genes of agronomic importance in
      resistance rice breeding. In this study, three resistance genes (Xa4 + xa5 +
      Xa21) were transferred from an indica donor (IRBB57), using a marker-assisted
      backcrossing (MAB) breeding strategy, into a BB-susceptible elite japonica rice
      cultivar, Mangeumbyeo, which is high yielding with good grain quality. RESULTS:
      Our analysis led to the development of three elite advanced backcross breeding
      lines (ABL) with three resistance genes by foreground and phenotypic selection in
      a japonica genetic background without linkage drag. The background genome
      recovery of the ABL expressed more than 92.1% using genome-wide SSR marker
      analysis. The pathogenicity assays of three resistance-gene-derived ABL were
      conducted under glasshouse conditions with the 18 isolates of Xoo prevalent in
      Korea. The ABL exhibited very small lesion lengths, indicating a hypersensitive
      reaction to all 18 isolates of Xoo, with agronomic and grain quality traits
      similar to those of the recurrent parent. Pyramiding the resistance genes Xa4,
      xa5 and Xa21 provided a higher resistance to Xoo than the introduction of the
      individual resistance genes. Additionally, the combination of two dominant and
      one recessive BB resistance gene did not express any negative effect on agronomic
      traits in the ABL. CONCLUSIONS: The strategy of simultaneous foreground and
      phenotypic selection to introduce multiple R genes is very useful to reduce the
      cost and the time required for the isolation of desirable recombinants with
      target resistance genes in rice. The resistance-gene-derived ABL have practical
      breeding value without a yield penalty by providing broad-spectrum resistance
      against most of the existing isolates of BB in South Korea and will have a high
      impact on the yield stability and sustainability of rice productivity.

PMID- 24280419
TI  - Exonuclease 1 is essential for maintaining genomic stability and the
      proliferative capacity of neural but not hematopoietic stem cells.
AB  - Exonuclease 1 (Exo1) has been implicated in the regulation of DNA damage
      responses in stem cells with dysfunctional telomeres. However, it is unclear
      whether Exo1-mediated DNA maintenance pathways play a role in the maintenance of
      genomic stability and the self-renewal of tissue stem cells in mice with
      functional telomeres. Here, we analyzed the proliferative capacity of neural stem
      cells (NSCs) and hematopoietic stem cells (HSCs) from Exo1(-/-) mice. Our study
      shows that Exo1 deficiency impairs the maintenance of genomic stability and
      proliferative capacity in NSCs but not HSCs. In line with these results, we
      detected a decrease in proliferation and an up-regulation of p21 expression
      levels in Exo1-deficient NSCs but not Exo1-deficient HSCs. Our data provide
      experimental evidence that Exo1 deficiency has a differential impact on the
      homeostasis and proliferative capacity of tissue stem cells in the brain and bone
      marrow, suggesting that different tissue stem cells utilize distinct mechanisms
      for maintaining their genomic stability. Our current study provides important
      insight into the role of Exo1-mediated DNA maintenance pathways in the
      maintenance of genomic stability and the proliferative capacity of tissue stem
      cells. 

PMID- 24280418
TI  - Electrophysiological properties of neurosensory progenitors derived from human
      embryonic stem cells.
AB  - In severe cases of sensorineural hearing loss where the numbers of auditory
      neurons are significantly depleted, stem cell-derived neurons may provide a
      potential source of replacement cells. The success of such a therapy relies upon
      producing a population of functional neurons from stem cells, to enable precise
      encoding of sound information to the brainstem. Using our established
      differentiation assay to produce sensory neurons from human stem cells, patch
      clamp recordings indicated that all neurons examined generated action potentials
      and displayed both transient sodium and sustained potassium currents. Stem cell
      derived neurons reliably entrained to stimuli up to 20 pulses per second (pps),
      with 50% entrainment at 50 pps. A comparison with cultured primary auditory
      neurons indicated similar firing precision during low-frequency stimuli, but
      significant differences after 50 pps due to differences in action potential
      latency and width. The firing properties of stem cell-derived neurons were also
      considered relative to time in culture (31-56 days) and revealed no change in
      resting membrane potential, threshold or firing latency over time. Thus, while
      stem cell-derived neurons did not entrain to high frequency stimulation as
      effectively as mammalian auditory neurons, their electrical phenotype was stable
      in culture and consistent with that reported for embryonic auditory neurons.

PMID- 24280420
TI  - Tetracyclines cause cell stress-dependent ATF4 activation and mTOR inhibition.
AB  - Tetracyclines have long been used as valuable broad-spectrum antibiotics. The
      high antibacterial activity of tetracyclines, combined with their good
      tolerability, has led to their widespread use in treating various infectious
      diseases. However, similar to other antibiotics, tetracyclines are also known for
      their adverse effects on different human tissues, including hepatic steatosis. We
      observed that tetracyclines, including doxycycline and minocycline, caused
      enhanced expression of the liver chalone inhibin betaE in HepG2 cells, mediated
      by the cell stress-regulated transcription factor ATF4. ATF4 and its target genes
      ATF3, CHOP, and inhibin betaE are involved in cell cycle control, cell survival,
      cell metabolism, and modulation of cytokine expression. Furthermore, we observed
      that long term tetracycline incubation also caused inhibition of the mTOR
      complex, a central regulator of cell metabolism, further contributing to the
      observed cell-cycle arrest and autophagy in doxycycline- and minocycline-treated
      cell lines. ATF4 activation and mTOR inhibition link two crucial regulators of
      the cellular stress response and cell metabolism to the effects of tetracyclines
      on eukaryotic cell metabolism, and may help to understand the antibiotic
      independent influence of these drugs on human tissues. Since the observed effects
      of tetracyclines on human cells were also found to be dependent on the magnesium
      ion concentrations supplied, the data further indicate the importance of
      magnesium supplementation to reduce or prevent side effects of long term
      treatment with tetracyclines. 

PMID- 24280421
TI  - Exploring the response of rice (Oryza sativa) leaf to gibberellins: a proteomic
      strategy.
AB  - BACKGROUND: Gibberellins (GAs) are plant-specific hormones that play a central
      role in the regulation of growth and development with respect to environmental
      variability. Plants respond to GAs signal through various biochemical and
      physiological processes. To better understand the response for GA signal, we
      carried out a proteomic study in rice (Oryza sativa L. spp. japonica) leaf.
      RESULTS: Through two-dimensional gel electrophoresis (2-DE) and mass spectroscopy
      analysis, we identified 61 proteins as GA-responsive. These proteins were
      annotated in various biological functions, such as signal transduction and cell
      growth/division, photosynthesis and energy metabolism, protein stability and
      defense. Among these, photosynthetic proteins decreased while many catabolic
      proteins increased. In addition, GA up-regulated a variety of cell
      growth/division, protein stability and defense proteins such as cell division
      cycle protein 48, molecular chaperones, and catalases. CONCLUSION: This is the
      first report that cell division cycle protein 48 may be responsible for leaf
      expansion after leaf sensing GA signal. The results presented here provide new
      insight into the mechanism of rice leaf in response to GA signal.

PMID- 24280422
TI  - Evaluation of the rearfoot component (module 3) of the ACFAS scoring scale.
AB  - The American College of Foot and Ankle Surgeons (ACFAS) scoring scale modules 3
      and 4 have not been validated or tested against other validated instruments
      widely used in medical and surgical research and practice. The purpose of the
      present study was to evaluate the rearfoot component (module 3) of the ACFAS
      scoring system by assessing its correlation against well-established instruments.
      A modified ACFAS scale (mACFAS), Medical Outcomes Study 36-item short form (SF
      36), version 2 (SF-36v2), and the short form of the International Physical
      Activity Questionnaire (IPAQ) were administered to subjects enrolled in our
      ongoing longitudinal cohort flatfoot study. Eighty-six patients were evaluated.
      The mACFAS correlated moderately to highly with the SF-36v2 physical component
      score and moderately with the mental component score and IPAQ. When divided into
      higher arched, lower arched, and rectus foot groups, the mACFAS correlated more
      strongly with the SF-36v2 and correlated with the IPAQ in the lower arched
      population. The results of the present study are promising for the rearfoot
      component of the ACFAS scoring scale, especially in the evaluation of the lower
      arched foot type. Future research should evaluate the disease- and symptom
      specific validity, responsiveness, and reproducibility of the mACFAS. 

PMID- 24280424
TI  - [Systemic inflammatory response syndrome and septic shock due to parvovirus B19
      in a healthy child].

PMID- 24280423
TI  - Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic
      glycolysis in cancer cells.
AB  - BACKGROUND: Most normal cells in the presence of oxygen utilize glucose for
      mitochondrial oxidative phosphorylation. In contrast, many cancer cells rapidly
      convert glucose to lactate in the cytosol, a process termed aerobic glycolysis.
      This glycolytic phenotype is enabled by lactate dehydrogenase (LDH), which
      catalyzes the inter-conversion of pyruvate and lactate. The purpose of this study
      was to identify and characterize potent and selective inhibitors of LDHA.
      METHODS: High throughput screening and lead optimization were used to generate
      inhibitors of LDHA enzymatic activity. Effects of these inhibitors on metabolism
      were evaluated using cell-based lactate production, oxygen consumption, and 13C
      NMR spectroscopy assays. Changes in comprehensive metabolic profile, cell
      proliferation, and apoptosis were assessed upon compound treatment. RESULTS: 3
      ((3-carbamoyl-7-(3,5-dimethylisoxazol-4-yl)-6-methoxyquinolin-4-yl) amino)
      benzoic acid was identified as an NADH-competitive LDHA inhibitor. Lead
      optimization yielded molecules with LDHA inhibitory potencies as low as 2 nM and
      10 to 80-fold selectivity over LDHB. Molecules in this family rapidly and
      profoundly inhibited lactate production rates in multiple cancer cell lines
      including hepatocellular and breast carcinomas. Consistent with selective
      inhibition of LDHA, the most sensitive breast cancer cell lines to lactate
      inhibition in hypoxic conditions were cells with low expression of LDHB. Our
      inhibitors increased rates of oxygen consumption in hepatocellular carcinoma
      cells at doses up to 3 microM, while higher concentrations directly inhibited
      mitochondrial function. Analysis of more than 500 metabolites upon LDHA
      inhibition in Snu398 cells revealed that intracellular concentrations of
      glycolysis and citric acid cycle intermediates were increased, consistent with
      enhanced Krebs cycle activity and blockage of cytosolic glycolysis. Treatment
      with these compounds also potentiated PKM2 activity and promoted apoptosis in
      Snu398 cells. CONCLUSIONS: Rapid chemical inhibition of LDHA by these quinoline 3
      sulfonamids led to profound metabolic alterations and impaired cell survival in
      carcinoma cells making it a compelling strategy for treating solid tumors that
      rely on aerobic glycolysis for survival.

PMID- 24280425
TI  - [Pulmonary artery sling as a casual diagnosis].

PMID- 24280426
TI  - [Tinea capitis and dermatoscopy].

PMID- 24280427
TI  - [Anterior cervical hypertrichosis].

PMID- 24280428
TI  - [Sinus bradycardia secondary to the use of pulse corticosteroids].

PMID- 24280429
TI  - The orthotic treatment of acute and chronic disease of the cervical and lumbar
      spine.
AB  - BACKGROUND: Orthoses are external aids that are often used to treat pain and
      diseases affecting the spine, such as lumbago, whiplash, and disc herniation. In
      this review, we assess the effectiveness and complications of orthotic treatment
      for typical spinal conditions and after spinal surgery. The orthotic treatment of
      fractures and postural abnormalities are beyond the scope of this article.
      METHOD: This review is based on a selective search in the Medline database with
      consideration of controlled trials, systematic reviews, and the recommendations
      of the relevant medical societies. RESULTS: Three relevant systematic reviews and
      four controlled trials were found. Very few controlled trials to date have
      studied the efficacy of orthotic treatment compared to other conservative
      treatments and surgery. No definitive evidence was found to support the use of
      orthoses after surgery, in lumbar radiculopathy, or after whiplash injuries of
      the cervical spine. In a single trial, short-term immobilization was an effective
      treatment of cervical radiculopathy. Orthoses are not recommended for nonspecific
      low back pain. The potential complications of cervical orthoses include pressure
      related skin injuries and dysphagia. CONCLUSION: No definitive evidence as yet
      supports the use of orthoses after spinal interventions or in painful conditions
      of the cervical or lumbar spine. They should, therefore, be used only after
      individual consideration of the indications in each case.

PMID- 24280430
TI  - Pneumococcal vaccination rates in adults in Germany: an analysis of statutory
      health insurance data on more than 850,000 individuals.
AB  - BACKGROUND: The German Standing Committee on Vaccination Recommendations
      (Standige Impfkommission, STIKO) recommends standard vaccination against
      pneumococcal infections for all persons aged 60 or older, and for all persons of
      any age with an increased health risk. It is not known how many persons in the
      target group in Germany have actually been vaccinated. METHOD: We used claims
      data of a German statutory health insurance (Deutsche BKK) to determine
      pneumococcal vaccination rates, stratified by age and risk, for the one-year
      period 1 July 2008 to 30 June 2009. The number of influenza vaccinations in the
      same period was analyzed for comparison. Because pneumococcal vaccination does
      not need to be performed annually, the calculated rates are an underestimate of
      the percentage of persons who have been vaccinated. A simulation model was used
      to correct for persons vaccinated at earlier times. The vaccination rates were
      estimated on the basis of various scenarios. RESULTS: Data were obtained on 867
      683 persons aged 18 or older. According to an optimistic estimate, the percentage
      of pneumococcal vaccination in the overall population is 3.75% for persons aged
      18-59 and 50.89% for persons aged 60 and above (influenza: 8.80% and 41.15%,
      respectively). In persons at elevated risk, the rate of vaccination in the
      presence of at least one risk factor is 12.66% / 54.67% (influenza: 15.66% /
      39.96%). In persons with moderate risk, the vaccination rate is 16.02% / 56.75%
      (influenza: 18.54% / 40.61%); in persons whose elevated risk was high, it is
      8.93% / 52.21% (influenza: 7.37%/37.78%). The limitations of this study are the
      short study period and the inability to define the population at risk
      unambiguously. CONCLUSION: The rate of pneumococcal vaccination in adults in
      Germany is too low; at best, it is comparable to that of influenza vaccination.
      These results should be validated by nationwide monitoring of the pneumococcal
      vaccination program. For example, questions about pneumococcal vaccination could
      be included in the GEDA study (German Health Update) that is conducted annually
      by the Robert Koch Institute.

PMID- 24280431
TI  - Not a disease entity.

PMID- 24280432
TI  - In reply.

PMID- 24280433
TI  - Connections are clearly more complexy.

PMID- 24280434
TI  - In reply.

PMID- 24280435
TI  - Evaluacion de la Eficacia Anti-Caries de un Dentifrico con Arginina al 1.5% y
      1450ppm de Fluoruro como Monofluorofosfato de Sodio, Usando Fluorescencia
      Cuantitativa Inducida por Luz (QLF).

PMID- 24280436
TI  - Stable carbon isotope discrimination is under genetic control in the C4 species
      maize with several genomic regions influencing trait expression.
AB  - In plants with C4 photosynthesis, physiological mechanisms underlying variation
      in stable carbon isotope discrimination (Delta(13)C) are largely unknown, and
      genetic components influencing Delta(13)C have not been described. We analyzed a
      maize (Zea mays) introgression library derived from two elite parents to
      investigate whether Delta(13)C is under genetic control in this C4 species. High
      density genotyping with the Illumina MaizeSNP50 Bead Chip was used for a detailed
      structural characterization of 89 introgression lines. Phenotypic analyses were
      conducted in the field and in the greenhouse for kernel Delta(13)C as well as
      plant developmental and photosynthesis-related traits. Highly heritable
      significant genetic variation for Delta(13)C was detected under field and
      greenhouse conditions. For several introgression library lines, Delta(13)C values
      consistently differed from the recurrent parent within and across the two
      phenotyping platforms. Delta(13)C was significantly associated with 22 out of 164
      analyzed genomic regions, indicating a complex genetic architecture of
      Delta(13)C. The five genomic regions with the largest effects were located on
      chromosomes 1, 2, 6, 7, and 9 and explained 55% of the phenotypic variation for
      Delta(13)C. Plant development stage had no effect on Delta(13)C expression, as
      phenotypic as well as genotypic correlations between Delta(13)C, flowering time,
      and plant height were not significant. To our knowledge, this is the first study
      demonstrating Delta(13)C to be under polygenic control in the C4 species maize. 

PMID- 24280437
TI  - Can photodynamic therapy be the preferred treatment option for anal
      intraepithelial neoplasia? Initial results of a pilot study.
AB  - Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over
      time may progress to invasive anal squamous cell carcinoma. There is no standard
      treatment for AIN, but one of the therapeutic options available is photodynamic
      therapy (PDT). There are very few published studies of the efficacy of PDT, but
      it has been shown to produce downgrading of high-grade dysplasia in the anal
      region. The aim of the study was to evaluate the role of PDT in the treatment of
      AIN. Fifteen patients who received anal PDT between 2004 and 2013 were
      identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and
      one had dysplasia with high-risk human papillomavirus. After a median follow-up
      of nineteen months, ten of these have had at least one follow-up with aceto-white
      staining. Six of these ten patients had a complete response to PDT, although
      three subsequently had some recurrence. Three further patients had a partial
      response to PDT. There were no major therapeutic complications. Our findings
      suggest that PDT is a safe and feasible treatment option for AIN, associated with
      reasonable response rates and relatively little morbidity. Further research into
      the efficacy of PDT for AIN is required. 

PMID- 24280438
TI  - Early induction of stress-associated Src activator/Homo sapiens chromosome 9 open
      reading frame 10 protein following photodynamic therapy.
AB  - BACKGROUND: There are proteins, responsible for many basic cell functions
      (transmission of extracellular signals to cytoplasm or nucleus, cell growth,
      proliferation, migration, survival), which are activated and overexpressed in
      response to acute oxidative stress, especially tyrosine kinases. The oxidative
      stress-associated Src activator/Homo sapiens chromosome 9 open reading frame 10
      protein (Ossa/C9orf10) protects cancer cells from oxidative stress-induced
      apoptosis by Src family kinases activation. METHODS: In this study precursor of
      protoporphyrin IX, 5-aminolevulinic acid and its encapsulated form were used in
      treating MCF-7 human breast cancer cells. After light illumination, cells were
      collected at different time points and used for evaluation (immunocytochemistry,
      Western blot analysis) of expression of above proteins, c-Src and Ossa. RESULTS:
      Our results showed that 5-aminolevulinic acid-mediated photodynamic therapy
      caused decrease of c-Src expression at 7h after irradiation. The strongest
      expression was observed at 24h after treatment. Encapsulated form of 5
      aminolevulinic acid in terms of PDT caused similar changes of expression of c-Src
      protein. Furthermore, we observed strong Ossa expression at 7h after treatment in
      comparison to very low expression at time points 0, 18 and 24h. CONCLUSION: We
      would like to emphasize that our results showed high expression of Ossa at early
      time interval after PDT, which was accompanied by a low expression of c-Src
      kinase, what could protect cancer cells from PDT through activation of c-Src in
      response to oxidative stress.

PMID- 24280439
TI  - Optical coherence tomography imaging of non-melanoma skin cancer undergoing
      photodynamic therapy reveals subclinical residual lesions.
AB  - BACKGROUND: Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a
      widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC).
      The outcome of MAL-PDT is usually primarily evaluated clinically. Optical
      coherence tomography (OCT) is a non-invasive imaging technology based on
      interferiometry. OCT has been proven to provide high accuracy in identifying NMSC
      lesions and performing thickness measurements of thin tumours. OBJECTIVES: To
      describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and
      to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC
      lesions. METHODS: A total of 18 biopsy-proven basal cell carcinomas and actinic
      keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3
      months follow-up the patients were assessed both by OCT and clinically. If the
      clinical and OCT evaluation came to different conclusions on recurrence of the
      lesion, patients were followed more closely at clinical appointments for up to
      one year after the PDT treatment. RESULTS: All lesions displayed at least one OCT
      characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was
      suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly
      identified all of the partial responses also found by the clinical examinations.
      In both cases where recurrence was only found in OCT, this was subsequently
      confirmed by histology. CONCLUSIONS: Our study suggests that OCT identified 29%
      more recurrences than clinical examination alone. OCT can detect subclinical
      residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate
      tool for early detection of residual lesional tissue.

PMID- 24280440
TI  - Tissue-engineered tracheal reconstruction using chondrocyte seeded on a porcine
      cartilage-derived substance scaffold.
AB  - OBJECTIVES: Tracheal reconstruction with tissue-engineering technique has come
      into the limelight in the realm of head and neck surgery. We intended to evaluate
      the plausibility of allogenic chondrocytes cultured with porcine cartilage
      derived substance (PCS) scaffold for partial tracheal defect reconstruction.
      METHODS: Powder made from crushed and decellularized porcine articular cartilage
      was formed as 5 mm * 12 mm (height * diameter) scaffold. Chondrocytes from rabbit
      articular cartilage were expanded and cultured with PCS scaffold. After 7 weeks
      culture, the scaffolds were implanted on a 5 mm * 10 mm artificial tracheal
      defect in six rabbits. Two, four and eight weeks postoperatively, the sites were
      evaluated endoscopically, radiologically, histologically and functionally.
      RESULTS: None of the six rabbits showed any sign of respiratory distress.
      Endoscopic examination did not show any collapse or blockage of the reconstructed
      trachea and the defects were completely covered with regenerated respiratory
      epithelium. Computed tomography showed good luminal contour of trachea.
      Postoperative histologic data showed that the implanted chondrocyte successfully
      formed neo-cartilage with minimal inflammatory response and granulation tissue.
      Ciliary beat frequency of regenerated epithelium was similar to those of normal
      adjacent mucosa. CONCLUSIONS: The shape and function of reconstructed trachea
      using allogenic chondrocytes cultured with PCS scaffold was restored successfully
      without any graft rejection.

PMID- 24280441
TI  - Applicability of spectral gradient acoustic reflectometry (EarCheck): screening
      patients who need surgical treatment for chronic otitis media with effusion.
AB  - OBJECTIVES: We aimed to conduct a prospective, observational study of the
      applicability of EarCheck (Innovia Medical LLC, Omaha, NE) in the surgical
      management of chronic otitis media with effusion (COME). MATERIALS AND METHODS:
      Between February 2013 and July 2013, 84 patients (165 ears) who had been
      diagnosed with COME and underwent surgical management were recruited. Information
      concerning patient sex, age, body mass index, EarCheck score, pure-tone averages
      (PTAs), speech reception thresholds (SRTs), and characteristics of middle ear
      fluid (MEF) were documented and statistically analyzed. RESULTS: MEF was detected
      in 87.3% (n=144/165) of the 165 ears. Based on EarCheck scores >= 3 (as a
      criterion for abnormal findings), the sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and accuracy of EarCheck
      were 56.9%, 90.5%, 82%, 23.5%, and 61.2%, respectively. Significant positive
      correlation was found between EarCheck, both pure-tone thresholds at all
      frequencies and mean PTAs, and SRTs. The mean PTAs and SRTs of the patients with
      EarCheck scores >= 3 was 37.79 dB and 33.26 dB, respectively; these scores were
      significantly higher than the mean PTAs and SRTs (30.56 dB and 25.88 dB,
      respectively) of the patients with EarCheck scores <3 (p<0.05). CONCLUSION:
      Although it is not preferable to conduct the EarCheck test alone when diagnosing
      COME because of its low accuracy, because of its additional hearing level clues,
      EarCheck can be used in deciding whether to perform tympanostomy tube insertion
      when conventional audiometry is not possible.

PMID- 24280442
TI  - Huai Qi Huang ameliorates proteinuria and hematuria in mild IgA nephropathy
      patients: a prospective randomized controlled study.
AB  - BACKGROUND/PURPOSE: Huai Qi Huang (HQH) is a compound Chinese herbal medicine
      that contains Trametes robiniophila murr, wolfberry fruit, and Polygonatum. In
      the present study, we investigated the effects of HQH on patients with mild
      immunoglobulin A nephropathy (IgAN) through a prospective randomized controlled
      study. METHODS: Forty-five adults diagnosed with IgAN according to renal
      pathology, who had hematuria or/and proteinuria (<= 2 g/day), were randomly
      assigned to receive HQH or no treatment for 12 weeks. Twenty-four hour urinary
      protein excretion and hematuria were measured at Weeks 0, 4, 8, and 12. The rate
      of complete remission of proteinuria and hematuria was evaluated. Any adverse
      events induced by HQH were also observed during the treatment period. RESULTS:
      Twenty-four hour urinary protein excretion was significantly reduced by HQH
      treatment compared with that in the control group at Weeks 8 and 12. A much
      higher rate of complete remission of proteinuria was observed in the HQH group
      than in control group at Week 12. HQH administration also obviously reduced the
      extent of hematuria compared with that in the control group at Week 12. HQH
      treatment dramatically increased the rate of complete remission of hematuria
      compared with that in control group at Weeks 8 and 12. No obvious adverse events
      caused by HQH were observed. CONCLUSION: HQH could be a new conservative therapy
      for IgAN patients who cannot tolerate steroids and immunosuppressive agents. The
      relapse rate after discontinuing treatment still needs further investigation.

PMID- 24280443
TI  - Tuberculous choledochoduodenal fistula with extrahepatic portal vein obstruction:
      rare association.

PMID- 24280444
TI  - Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional
      study.
AB  - AIMS: To evaluate the modified dosages of anti-TNF in controlling disease
      activity in rheumatoid arthritis (RA) measured by DAS28-ESR. PATIENTS AND
      METHODS: Cross-sectional study: RA patients treated with etanercept (ETN),
      adalimumab (ADA) or infliximab (IFX), at standard or modified doses. MAIN
      VARIABLES: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR.
      RESULTS: 195 RA patients included (79% women, mean age 58.1 years): ETN=81,
      ADA=56, IFX=58. Mean disease duration and time to first biological treatment was
      higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN
      (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%);
      reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in
      ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders
      (DAS28 <=3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). CONCLUSIONS: RA
      clinical control can be preserved with modified anti-TNF dosages. Controlled
      prospective studies should be performed to define when therapy can be tailored
      and for which patients.

PMID- 24280445
TI  - Incongruent object/context relationships in visual scenes: where are they
      processed in the brain?
AB  - Rapid object visual categorization in briefly flashed natural scenes is
      influenced by the surrounding context. The neural correlates underlying reduced
      categorization performance in response to incongruent object/context associations
      remain unclear and were investigated in the present study using fMRI.
      Participants were instructed to categorize objects in briefly presented scenes
      (exposure duration=100ms). Half of the scenes consisted of objects pasted in an
      expected (congruent) context, whereas for the other half, objects were embedded
      in incongruent contexts. Object categorization was more accurate and faster in
      congruent relative to incongruent scenes. Moreover, we found that the two types
      of scenes elicited different patterns of cerebral activation. In particular, the
      processing of incongruent scenes induced increased activations in the
      parahippocampal cortex, as well as in the right frontal cortex. This higher
      activity may indicate additional neural processing of the novel (non experienced)
      contextual associations that were inherent to the incongruent scenes. Moreover,
      our results suggest that the locus of object categorization impairment due to
      contextual incongruence is in the right anterior parahippocampal cortex. Indeed
      in this region activity was correlated with the reaction time increase observed
      with incongruent scenes. Representations for associations between objects and
      their usual context of appearance might be encoded in the right anterior
      parahippocampal cortex. 

PMID- 24280446
TI  - Short- and long-term neurocognitive functioning after electroconvulsive therapy
      in depressed elderly: a prospective naturalistic study.
AB  - BACKGROUND: It is generally assumed that the elderly patients are more vulnerable
      to cognitive side effects after electroconvulsive therapy (ECT) than younger
      depressed patients. The current study aims to evaluate the nature and extent of
      changes across multiple domains of neurocognitive functioning in a group of
      elderly depressed patients after ECT. METHODS: In this prospective naturalistic
      study, we included 42 depressed patients aged >=55 years. Global cognitive
      function, memory, and executive function were assessed before ECT treatment and
      within one week (short-term post-ECT) and six months after ECT (long-term post
      ECT). Associations between cognitive functioning and electrode placement, total
      number of treatment sessions, age, and the severity of depression at the time of
      cognitive measurement were studied. RESULTS: Our data offered no evidence of
      decline for any of the neurocognitive tests after ECT, given its power to detect
      the difference. Post-ECT improvement of neurocognitive functioning was
      statistically significant for the Mini-Mental State Examination, Visual
      Association Test, 10 Words Verbal Learning Test, and Expanded Mental Control
      Test. Effect sizes were medium to large. After six months, compared with post-ECT
      performance, statistically significant improvement was found only for the Trail
      Making Test-A and the Letter Fluency Test with small to medium effect sizes.
      CONCLUSIONS: In our severely depressed elderly patients, neurocognitive
      performance improved or did not change after ECT. Patients with poor cognitive
      function were not able to participate in neuropsychological assessment before ECT
      started. Consequently these results may not apply to patients with more severe
      cognitive impairment prior to the start of ECT.

PMID- 24280447
TI  - Laparoscopic restorative proctocolectomy with ileal J-pouch creation through the
      umbilical port.

PMID- 24280448
TI  - An advanced look at surgical performance under Medicare's hospital-inpatient
      value-based purchasing program: who is winning and who is losing?
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) is beginning to
      shift from paying providers based on volume to more explicitly rewarding quality
      of care. The hospital value-based purchasing (VBP) program is the first in a
      series of mandatory programs to financially reward and penalize US hospitals
      based on quality measure performance. Our objective was to identify the
      characteristics of hospitals that perform well (and those that perform poorly) on
      the surgical measures in CMS' hospital VBP program. STUDY DESIGN: Using 2008 to
      2010 performance data from CMS' Hospital Compare website and the 2009 American
      Hospital Association annual survey, we examined surgical measure performance for
      all acute care general hospitals in the US. Outcomes were determined by a
      composite surgical performance score indicating the percentage of eligible
      surgical performance points that a hospital received. RESULTS: There were 3,030
      hospitals included in our study. Composite surgical performance scores were 15.6%
      lower at public hospitals than at for-profit hospitals (p < 0.01). Additionally,
      there were significant differences in the routes by which hospitals achieved
      points, with smaller hospitals, for-profit hospitals, Magnet hospitals, and NSQIP
      hospitals all more likely to obtain points via the achievement route.
      CONCLUSIONS: The results of our study indicate that public hospitals perform
      worse on the surgical measures in the hospital VBP program. This study raises
      important questions about the impact that this new, mandatory program will have
      on public hospitals, which serve an important safety-net role and appear to be
      disadvantaged in the hospital VBP program. This issue should continue to be
      investigated as these mandatory quality programs are updated in future years.

PMID- 24280449
TI  - Intracorporeal uncut Roux-en-Y gastrojejunostomy reconstruction in pure single
      incision laparoscopic distal gastrectomy for early gastric cancer: unaided
      stapling closure.

PMID- 24280450
TI  - Evaluation of zinc (II) chelators for inhibiting p53-mediated apoptosis.
AB  - In a previous study, we reported that sodium orthovanadate (vanadate) is the
      first known inhibitor that is capable of protecting mice from death from the
      radiation-induced gastrointestinal syndrome via its ability to block both
      transcription-dependent and transcription-independent p53 apoptotic pathways. In
      this paper, we report that vanadate has a unique activity for inducing the
      denaturation of p53 relative to other known radioprotective p53 inhibitors,
      pifithrin-alpha (PFTalpha) and pifithrin-u (PFTu). This potent radioprotective
      effect of vanadate prompted us to undertake a more extensive search for p53
      inhibitors that can induce p53 denaturation. Based on the fact that p53
      denaturation can be induced by the dissociation of a zinc ion, which is used as a
      structural factor of p53, we screened some zinc (II) chelators for the
      suppression of the DNA binding activity of p53 in vitro and the inhibition of
      radiation-induced p53-dependent apoptosis in MOLT-4 cells. The findings indicate
      that two of five zinc (II) chelators also suppressed apoptosis. Among the
      inhibitors tested, Bispicen (N,N'-Bis(2-pyridylmethyl)-1,2-ethanediamine) had the
      highest inhibition activity. A mechanistic study using cells bearing different
      p53 status or functions (i.e., p53-knockdown MOLT-4 transformant and its
      revertants, p53 mutant cells, p53-null cells), and p53-independent apoptotic
      stimuli revealed that the suppressive effect of Bispicen on apoptosis is
      specifically mediated through p53. Moreover, Bispicen, similar to vanadate,
      induces the denaturation of p53 as well as the blocking of both transcription
      dependent and -independent apoptotic pathways. Our findings indicate that the use
      of zinc (II) chelators represent a new approach for protecting against radiation
      induced p53-dependent apoptosis through the inhibition of p53-dependent apoptotic
      pathways. 

PMID- 24280451
TI  - SNP-based analysis of genetic diversity in anther-derived rice by whole genome
      sequencing.
AB  - BACKGROUND: Anther culture has advantage to obtain a homozygous progeny by
      induced doubling of haploid chromosomes and to improve selection efficiency for
      invaluable agronomical traits. Therefore, anther culturing is widely utilized to
      breed new varieties and to induce genetic variations in several crops including
      rice. Genome sequencing technologies allow the detection of a massive number of
      DNA polymorphism such as SNPs and Indels between closely related cultivars. These
      DNA polymorphisms permit the rapid identification of genetic diversity among
      cultivars and genomic locations of heritable traits. To estimate sequence
      diversity derived from anther culturing, we performed whole-genome resequencing
      of five Korean rice accessions, including three anther culture lines (BLB, HY-04
      and HY-08), their progenitor cultivar (Hwayeong), and an additional japonica
      cultivar (Dongjin). RESULTS: A total of 1,165 * 106 raw reads were generated with
      over 58* coverage that detected 1,154,063 DNA polymorphisms between the Korean
      rice accessions and Nipponbare. We observed that in Hwayeong and its progenies,
      0.64 SNP was found per one kb of Nipponbare genome, while Dongjin, bred by a
      conventional breeding method, had a lower number of SNPs (0.45 SNP/kb). Among
      1,154,063 DNA polymorphisms, 29,269 non-synonymous SNPs located on 30,013 genes
      and these genes were functionally classified based on gene ontology (GO). We also
      analyzed line-specific SNPs which were estimated 1 ~ 3% of the total SNPs. The
      frequency of non-synonymous SNPs in each accession ranged from 26 SNPs in
      Hwayeong to 214 SNPs in HY-04. CONCLUSIONS: The genetic difference we detected
      between the progenies derived from anther culture and their mother cultivar is
      due to somaclonal variation during tissue culture process, such as karyotype
      change, chromosome rearrangement, gene amplification and deletion, transposable
      element, and DNA methylation. Detection of genome-wide DNA polymorphisms by high
      throughput sequencer enabled to identify sequence diversity derived from anther
      culturing and genomic locations of heritable traits. Furthermore, it will provide
      an invaluable resource to identify molecular markers and genes associated with
      diverse traits of agronomical importance.

PMID- 24280452
TI  - Single-feature polymorphism mapping of isogenic rice lines identifies the
      influence of terpene synthase on brown planthopper feeding preferences.
AB  - BACKGROUND: Bph3, a major brown planthopper (BPH) resistance locus derived from
      the rice cultivar Rathu Heenati (RH), has been used as a stable donor of traits
      that improve highly susceptible aromatic rice varieties in Thailand. Map-based
      cloning was initiated using a set of isogenic lines (ILs) harboring the major
      Bph3 locus on chromosome 6. IL genomes were scanned with a 57 K Affymetrix Rice
      GeneChip to identify the gene responsible for Bph3. FINDINGS: Single-feature
      polymorphism (SFP) mapping was used to localize 84 candidate genes. An expression
      analysis of 15 selected candidate genes in the aromatic rice cultivar KDML105
      (KD) and the ILs under normal conditions revealed two differentially expressed
      sequences. Following hopper feeding, only one candidate gene, Os04g27430, was
      differentially expressed. Os04g27430 encodes a putative sesquiterpene synthase
      (STPS) gene that was induced by BPH feeding in ILs. An antixenosis test in three
      selected ILs revealed a major role for STPS in insect preference during the first
      120 hours of the rice-insect interaction. Functional SNPs in exon 5 that resulted
      in the deletion of seven amino acids in the susceptible rice line were
      identified. Moreover, three additional SNPs associated with three transcription
      binding sites were also identified, which might explain the differential response
      of Os04g27430 during the anti-feeding test. CONCLUSION: Os04g27430 is the second
      known rice STPS induced by BPH. The gene may involve an antixenosis BPH
      resistance mechanism. The combination of the STPS and the Bph3 locus was more
      effective than Bph3 alone in the tested ILs.

PMID- 24280453
TI  - Anti-angiogenic effect of the basement membrane protein nidogen-1 in a mouse
      model of choroidal neovascularization.
AB  - In patients with age-related macular degeneration disruption of the integrity of
      the retinal pigment epithelium (RPE) and Bruch's membrane (BrM), precedes
      choroidal neovascularization (CNV). We investigated the role of the basement
      membrane (BM) proteins nidogen-1 and nidogen-2 for the development of
      experimental CNV. Laser-induced CNV was studied in Nid1(-/-) and Nid2(-/-) mice
      and wild type (WT) controls by fluorescein angiography, by immune histochemistry
      of flat-mounts or paraffin sections to analyze expression pattern of nidogen-1
      and -2 and nidogen binding BM proteins, and by western blotting. The influence of
      VEGF and bFGF on the mRNA expression of nidogen-1 was studied in vitro. Nidogen-1
      protein is present in the BM of the inner limiting membrane (ILM), the retinal
      capillaries, and the choroid/sclera and CNV. Nidogen-2 protein is also found in
      these BMs but with a weaker expression in the ILM. In the retina the absence of
      nidogen-1 does not influence the expression of nidogen-2 and vice versa and does
      not influence the expression of the BM components collagen IV, laminin gamma1,
      and perlecan. In Nid1(-/-) mice, CNV lesions showed increased vessel leakage
      during angiography and the CNV area was larger than in WT or nidogen-2 deficient
      mice. Laser treatment led to up-regulation of nidogen-1 protein expression in the
      sclera/choroid of nidogen-2 deficient or WT mice. The treatment of HUVECs with
      VEGF leads to a reduced expression of nidogen-1 mRNA whereas its expression
      remained unchanged in RPE cells. In conclusion, nidogen-1 produced by the
      endothelial cells acts as a factor to help stabilizing the BM, thus preventing
      the sprouting of new vessels or the infiltration of endothelial cells. In this
      sense nidogen-1 is essential to provide an anti-angiogenic environment of
      differentiated vessels. 

PMID- 24280454
TI  - The changing landscape of multiple myeloma: implications for oncology nurses.
AB  - Scientific advancements relative to diagnostic evaluation, risk-adapted treatment
      selection, and supportive care strategies for multiple myeloma (MM) have been
      developed in the past decade, which provides hope for patients living with MM.
      However, the disease remains incurable for the majority of patients, and
      continued clinical trials are necessary to refine existing therapeutic strategies
      and develop new approaches to treatment. Hematopoietic stem cell transplantation
      (HSCT), in particular autologous HSCT, remains an important component in the
      overall treatment paradigm for MM. This requires a well-organized team approach
      with ongoing communications and collaboration with community providers and other
      specialists. The majority of care for patients with MM is provided in the
      outpatient setting, relying on the active participation of both the patient and
      caregiver(s) for successful clinical outcomes. This supplement is prepared by
      members of the International Myeloma Foundation Nurse Leadership Board, which is
      dedicated to improving the care of patients with MM and their caregivers. The
      introduction serves to provide an overview of MM today and to summarize the
      articles included in this supplement. 

PMID- 24280455
TI  - Autologous hematopoietic stem cell transplantation for patients with multiple
      myeloma: an overview for nurses in community practice.
AB  - Autologous hematopoietic stem cell transplantation (AHSCT) is approved for the
      treatment of select solid tumors, autoimmune disorders, and most hematologic
      malignancies. Multiple myeloma (MM) is the most common indication for AHSCT.
      Despite improvement in response and survival rates in the era of novel agents,
      AHSCT remains an important treatment option for patients with MM who are
      eligible. Clinical management of patients with MM requires a multidisciplinary
      approach that incorporates healthcare professionals in a number of clinical
      settings as well as caregivers and the patient. Patients about to undergo AHSCT
      are generally referred to tertiary care centers that specialize in ASCT. Pre- and
      post-transplantation treatments and long-term follow-up often are managed by a
      community-based referring oncologist in collaboration with the transplantation
      team. Oncology nurses play an integral role in the care of patients with MM in
      each clinical setting. This article aims to provide non-transplantation oncology
      nurses with guidelines for education, clinical management, and support of
      patients with MM undergoing AHSCT with a primary focus on the pre- and post
      transplantation period. 

PMID- 24280456
TI  - Caregivers of multiple myeloma survivors.
AB  - Patients living with multiple myeloma (MM) face complex decisions throughout
      their journey relative to their diagnosis, options for treatment, and how their
      disease and treatment choices may affect them physically, emotionally,
      financially, and spiritually. Patients considering a hematopoietic stem cell
      transplantation face specific self-management challenges. The availability of a
      reliable caregiver is a prerequisite to transplantation eligibility. Currently,
      the majority of clinical management is episodic and provided in the outpatient
      setting. Therefore, the bulk of care for patients living with MM is provided by
      the patient together with his or her caregivers. Caregivers face similar
      challenges to those faced by the patient living with MM. They are required to
      take in complex information, perform often complicated or technical procedures
      such as line care or injections, assist the patient with activities of daily
      living, and attend the myriad of appointments required. Understanding the
      dynamics of the patient-caregiver relationship, the strengths and weaknesses
      unique to that relationship, common elements of caregiver stress or strain, and
      available tools and strategies to promote a sense of control and enhance self
      management skills may improve the health-related quality of life for both the
      patient with MM and his or her caregiver. 

PMID- 24280457
TI  - Clinical updates in blood and marrow transplantation in multiple myeloma.
AB  - The process of hematopoietic stem cell transplantation (HSCT) is well defined,
      yet debate remains surrounding the role and timing of HSCT in patients with
      multiple myeloma (MM). Since the 1980s, survival advances have been made with the
      use of newer agents by recognizing the role of transplantation, identifying the
      anticipated side effects at each phase, and improving supportive care strategies.
      Data support transplantation as part of the treatment strategy, but the optimal
      induction regimen and timing of transplantation have yet to be defined. The
      general consensus is that eligible patients should undergo autologous HSCT at
      some point in the treatment spectrum, preferably earlier rather than later in the
      disease. Allogeneic transplantation is only recommended in the context of a
      clinical trial and in patients with high-risk disease. The transplantation
      process can be overwhelming for patients and caregivers. Nurses play a key role
      in improving outcomes by caring for patients and families throughout the
      transplantation experience and, therefore, need to be knowledgeable about the
      process. This article is intended to expand discussion on the role of nurses in
      assisting patients and families undergoing transplantation to include an overview
      of the acute care phase of the transplantation process. 

PMID- 24280458
TI  - Autologous hematopoietic stem cell transplantation for multiple myeloma:
      frequently asked questions.
AB  - When caring for patients with multiple myeloma, questions often arise about the
      role and timing of autologous hematopoietic stem cell transplantation. As a
      complement to the other articles in this supplement, as well as to ensure that
      readers are provided with the insight needed to feel comfortable speaking to
      patients and other practitioners about this topic, the authors address eight
      frequently asked questions about common decision points in the process of
      autologous hematopoietic stem cell transplantation as a treatment for patients
      with multiple myeloma. 

PMID- 24280459
TI  - Using the community health assessment to screen for continued driving.
AB  - This project used the interRAI based, community health assessment (CHA) to
      develop a model for identifying current elder drivers whose driving behavior
      should be reviewed. The assessments were completed by independent housing sites
      in COLLAGE, a non-profit, national senior housing consortium. Secondary analysis
      of data drawn from older adults in COLLAGE sites in the United States was
      conducted using a baseline assessment with 8042 subjects and an annual follow-up
      assessment with 3840 subjects. Logistic regression was used to develop a Driving
      Review Index (DRI) based on the most useful items from among the many measures
      available in the CHA assessment. Thirteen items were identified by the logistic
      regression to predict drivers whose driving behavior was questioned by others. In
      particular, three variables reference compromised decision-making abilities:
      general daily decisions, a recent decline in ability to make daily decisions, and
      ability to manage medications. Two additional measures assess cognitive status:
      short-term memory problem and a diagnosis of non-Alzheimers dementia. Functional
      measures reflect restrictions and general frailty, including receiving help in
      transportation, use of a locomotion appliance, having an unsteady gait, fatigue,
      and not going out on most days. The final three clinical measures reflect
      compromised vision, little interest or pleasure in things normally enjoyed, and
      diarrhea. The DRI focuses the review process on drivers with multiple cognitive
      and functional problems, including a significant segment of potentially troubled
      drivers who had not yet been publicly identified by others. There is a need for
      simple and quickly identified screening tools to identify those older adults
      whose driving should be reviewed. The DRI, based on the interRAI CHA, fills this
      void. Assessment at the individual level needs to be part of the backdrop of
      science as society seeks to target policy to identify high risk drivers instead
      of simply age-based testing. 

PMID- 24280460
TI  - Efficacy of magnetic capture in comparison with conventional DNA isolation in a
      survey of Toxoplasma gondii in wild house mice.
AB  - Toxoplasma gondii is a zoonotic parasite with a world-wide distribution. House
      mice (Mus musculus) play an important role as a reservoir host in the parasite
      life cycle. However, their detection in mouse brain is limited because the host
      potentially harbours only a few tissue cysts. In order to improve the diagnosis,
      we tested a novel protocol for T. gondii detection in mice and compared this
      technique to a standard PCR-based protocol using a commercial kit for DNA
      isolation. Efficacy of magnetic capture for isolation of T. gondii DNA from whole
      host brains was tested in brain samples of laboratory mice spiked with 1 up to
      10(4) tachyzoites. Real-time PCR revealed that even 1-5 tachyzoites can be
      detected after magnetic capture. Also this method is suitable to quantify
      parasite numbers in mouse brains with more than 10 tachyzoite equivalents. To
      assess the two techniques in wild mice, we employed a dataset consisting of 243
      individuals. The prevalence of T. gondii detected by magnetic capture and qPCR
      and by commercial isolation and PCR was 1.2% and 0%, respectively. The magnetic
      capture and quantitative PCR seems to be a highly sensitive and specific
      diagnostic method for both laboratory research and wild population surveys.

PMID- 24280461
TI  - Intestinal ciliated protozoa of the Asian elephant Elephas maximus Linnaeus, 1758
      with the description of Triplumaria izmirae n. sp.
AB  - Species composition and distribution of intestinal ciliates excreted in the feces
      of three Asian elephants living in Sasali National Park, Izmir, Turkey, were
      investigated. Seven ciliate genera consisting of 36 species were identified. This
      is the first report on intestinal ciliates in elephants living in Turkey; one new
      species, T. izmirae n. sp., was described. This new species has a special
      macronucleus shape, skeletal rod plates with two wings and posterior contractile
      vacuole lying beneath the dorsal left base of the tail flap. The buccal
      infraciliary bands of T. izmirae are similar to those of T. selenica and T.
      suwako known from elephants. Triplumaria ovina and Raabena bella occurred in
      highest percentages in two elephants, whereas Latteuria polyfaria was highest in
      the third one. Ciliate densities in the three fecal samples were 3.5, 1.5 and 5.0
      * 10(4)/mL.

PMID- 24280462
TI  - The importance of case histories for accepting and improving homeopathy.
AB  - Case histories are necessary besides other types of evidence to convince doctors
      of a specific type action of homeopathic medicines. Prognosis of treatment does
      not merely depend on efficacy. Some considerations based on consensus meetings
      about best cases and prospective research into the relationship between symptoms
      and result. Many data in homeopathic literature are unreliable because of wrong
      interpretation, insufficient numbers and confirmation bias. Causal relationship
      between medicine and 'cure' could be documented better. Extraordinary cases are
      not helpful to increase reproducibility. CONCLUSION: For acceptance and
      improvement of homeopathy cases should be reproducible. 'Normal' cases reflecting
      daily practice contribute more to this goal than extraordinary cases. Accuracy
      can be increased by larger samples of comparable cases. Causal relationship
      between medicine and improvement should be further explored.

PMID- 24280463
TI  - Effect of community-based yoga intervention on oxidative stress and glycemic
      parameters in prediabetes: a randomized controlled trial.
AB  - OBJECTIVES: To study the effectiveness of yoga intervention on oxidative stress,
      glycemic status, blood pressure and anthropometry in prediabetes. DESIGN:
      Randomized-controlled trial. PARTICIPANTS: Twenty nine prediabetes subjects aged
      30-75 years. SETTING: Yoga was conducted at 4 different community diabetes
      clinics in Mangalore, India. INTERVENTIONS: Participants were randomized to
      either 3-month yoga or wait-list control groups. MAIN OUTCOME MEASURES:
      Malondialdehyde, glutathione, vitamin C, vitamin E, superoxide dismutase, plasma
      glucose, glycated haemoglobin, BMI, waist circumference, waist-to-hip ratio and
      blood pressure. RESULTS: Yoga intervention resulted in a significant decline in
      malondialdehyde (p<0.001), relative to the control group. In comparison with the
      control, there was a significant improvement in BMI, waist circumference,
      systolic blood pressure and fasting glucose levels at follow-up. No significant
      improvement in glycated haemoglobin, waist-to-hip ratio or any of the
      antioxidants was observed. CONCLUSIONS: Yoga intervention may be helpful in
      control of oxidative stress in prediabetes subjects. Yoga can also be beneficial
      in reduction in BMI, waist circumference, systolic blood pressure and fasting
      glucose. Effect of yoga on antioxidant parameters was not evident in this study.
      The findings of this study need to be confirmed in larger trials involving active
      control groups.

PMID- 24280464
TI  - The effect of Benson's relaxation technique on the quality of sleep of Iranian
      hemodialysis patients: a randomized trial.
AB  - OBJECTIVE: This study was performed to evaluate the effectiveness of Benson's
      relaxation technique in the quality of sleep of hemodialysis patients. DESIGN: It
      was a randomized controlled trial with a pre-post-test design. A total of 86
      hemodialysis patients referring to hemodialysis units were assigned to either the
      intervention (receiving Benson's relaxation technique) or the control group
      (routine care) through block randomization. SETTING: The study was performed in
      two hemodialysis units affiliated to Shiraz University of Medical Sciences,
      Shiraz, Iran. INTERVENTION: The patients in the intervention group listened to
      the audiotape of Benson's relaxation technique twice a day each time for twenty
      minutes for eight weeks. MAIN OUTCOME MEASURES: The global score of Pittsburgh
      Sleep Quality Index (PSQI) as well as its components was computed in both the
      intervention and the control group before and at the 8th week of the
      intervention. RESULTS: The results of ANCOVA indicated significant differences
      between the two groups regarding the scores of Pittsburgh Sleep Quality Index
      subscales, such as sleep disturbance, daytime dysfunction, the use of sleep
      medication, and subjective sleep quality and as well as its global scores at the
      8th week of the intervention (p<0.05). CONCLUSIONS: This study highlighted the
      importance of Benson's relaxation technique in improvement of the sleep quality
      of the patients on hemodialysis. Thus, educational sessions are recommended to be
      planned on this cost effective and easy to use relaxation technique in order to
      improve hemodialysis patients' sleep quality. Further studies are needed to
      assess the effectiveness of this technique in other groups of patients.

PMID- 24280465
TI  - The sustaining effects of Tai chi Qigong on physiological health for COPD
      patients: a randomized controlled trial.
AB  - OBJECTIVES: To evaluate the sustaining effects of Tai chi Qigong in improving the
      physiological health for COPD patients at sixth month. DESIGN: A randomized
      controlled trial. Subjects were in three randomly assigned groups: Tai chi Qigong
      group, exercise group, and control group. SETTING: The 206 subjects were
      recruited from five general outpatient clinics. INTERVENTIONS: Tai chi Qigong
      group completed a 3-month Tai chi Qigong program. Exercise group practiced
      breathing and walking as an exercise. Control group received usual care. MAIN
      OUTCOME MEASURES: Primary outcomes included six-minute walking distance and lung
      functions. Secondary outcomes were dyspnea and fatigue levels, number of
      exacerbations and hospital admissions. RESULTS: Tai chi Qigong group showed a
      steady improvement in exercise capacity (P<.001) from baseline to the sixth
      month. The mean walking distance increased from 298 to 349 meters (+17%). No
      significant changes were noted in the other two groups. Tai chi Qigong group also
      showed improvement in lung functions (P<.001). Mean forced expiratory volume in
      1s increased from .89 to .99l (+11%). No significant change was noted in the
      exercise group. Deterioration was found in the control group, with mean volume
      decreased from .89 to .84l (-5.67%). Significant decreased in the number of
      exacerbations was observed in the Tai chi Qigong group. No changes in dyspnea and
      fatigue levels were noted among the three groups. CONCLUSIONS: Tai chi Qigong has
      sustaining effects in improving the physiological health and is a useful and
      appropriate exercise for COPD patients.

PMID- 24280466
TI  - The effective evaluation on symptoms and quality of life of chronic obstructive
      pulmonary disease patients treated by comprehensive therapy based on traditional
      Chinese medicine patterns.
AB  - OBJECTIVE: To evaluate the efficacy of comprehensive interventions based on the
      three TCM patterns on symptoms and quality of life of COPD patients. DESIGN: An
      open-label, randomized, controlled trial. SETTING: Four hospitals in China.
      INTERVENTION: 352 patients were randomly divided into two groups. Patients in the
      trial group were given conventional Western medicine and Bu-Fei Jian-Pi granules,
      Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules respectively; patients in the
      control group were given conventional Western medicine. Data collection was
      performed at baseline, in the 3rd and 6th month during the treatment period, and
      the 12th month during the follow-up period. OUTCOMES: Symptoms, including cough,
      sputum, pant, chest tightness, short of breath, lassitude, cyanosis and symptom
      total score; quality of life, measured by the WHOQOL-BREF questionnaire and adult
      COPD quality of life questionnaire (COPD-QOL). RESULTS: Of the 352 patients, 306
      fully completed the study. After treatment and follow-up, there were significant
      differences between two groups in the following: cough, sputum, pant, chest
      tightness, shortness of breath, lassitude score and symptom total score (P<.05);
      physical, psychological, social and environment domain (P<.05) of the WHOQOL
      BREF; daily living ability, social activity, depression symptoms and anxiety
      symptoms domain (P<.05) of the COPD-QOL. There were no differences between two
      groups in cyanosis and adverse events. CONCLUSION: Based on the TCM patterns, Bu
      Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have
      beneficial effects on symptoms and quality of life of COPD patients.

PMID- 24280467
TI  - Magnetotherapy in hand osteoarthritis: a pilot trial.
AB  - OBJECTIVE: To evaluate the effectiveness of magnetotherapy in the treatment of
      hand osteoarthritis (HO). METHODS: In this randomized controlled single-blind
      follow-up study, patients with HO were randomly assigned into 2 groups (G1 and
      G2). The subjects in G1 (n=25) received 25Hz, 450 pulse/s, 5-80G, magnetotherapy
      of totally 10 days and 20 min/day combined with active range of
      motion/strengthening exercises for the hand. G2 (n=25) received sham
      magnetotherapy for 20 min/day for the same duration combined with the same hand
      exercises. Outcome measures were pain and joint stiffness evaluation, handgrip
      and pinchgrip strength (HPS), Duruoz and Auscan Hand Osteoarthritis Indexes
      (DAOI) and Short Form-36 Health Questionnaire (SF-36) administered at baseline,
      immediately after treatment and at the follow up. RESULTS: When the groups were
      compared with each other, improvement observed in SF-36 Pain (p<0.001), SF-36
      Social Function (p=0.030), SF-36 Vitality (p=0.002), SF-36 General Health
      (p=0.001), Pain at rest (p<0.001), Pain at motion (p<0.001), Joint stiffness
      (p<0.001), DAOI (p<0.001) were in favor of G1. CONCLUSIONS: Changes in pain,
      function and quality of life scores showed significant advantage in favor of the
      applied electromagnetic intervention in patients with HO.

PMID- 24280468
TI  - Essential hypertension treated by wuling powder and modified tianma gouteng
      decoction: a cohort study without controls.
AB  - OBJECTIVE: To evaluate the efficacy and safety of wuling powder and modified
      tianma gouteng decoction as an open add-on therapy for treating essential
      hypertension (EH). METHODS: 72 cases of EH patients took wuling powder and
      modified tianma gouteng decoction for 2 weeks to treat EH without changing their
      former medication. New York Heart Association (NYHA) heart function
      classification, heart rate, blood pressure and 6-min walking test were evaluated
      before and after treatment. RESULTS: Wuling powder and modified tianma gouteng
      decoction decreased the EH patients' heart rate, systolic pressure, diastolic
      pressure and increased the 6-min walking distance very significantly (P<0.01).
      The total effective rate on blood pressure was 91.7%, and the total effective
      rate on NYHA heart function improvement was 95.1%. No serious side effect
      appeared. CONCLUSION: From this study, treating EH with wuling powder and
      modified tianma gouteng decoction as an open add-on therapy seems to be effective
      and safe. Further randomized trials are needed to test the positive findings.

PMID- 24280469
TI  - A clinical observation of irritable bowel syndrome treated by traditional Chinese
      spinal orthopedic manipulation.
AB  - OBJECTIVE: To evaluate the clinical effect of Traditional Chinese Spinal
      Orthopedic Manipulation (TCSOM) in treating Irritable Bowel Syndrome (IBS) in
      comparison with Pinaverium Bromide Dicetel (PBD), and to assess a possible cause
      for IBS. METHODS: 60 cases of IBS patients were randomly divided into two groups:
      TCSOM and PBD. All patients in the TCSOM group were treated with a 5-time spinal
      manipulations. The symptoms of pre-treatment and post-treatment were evaluated
      based on bowel symptom scale (BSS) scores. A symptom improvement rating (SIR) and
      patient subjective assessment (PSA) were implemented in order to evaluate the
      effects of the treatments, and to statistically compare the two groups. RESULTS:
      The symptoms of 23 patients of the TCSOM group disappeared soon after spinal
      manipulation and 6 cases were significantly improved. The BSS scores in the TCSOM
      group were significantly lower than those in the PBD group post-treatment.
      According to the SIR which was based on the BSS, the TCSOM research group
      included 14 cases with excellent results, 13 cases with good, and 3 cases with
      poor. Adverse side effects to the treatment were not reported. Based on the BSS,
      the PBD research group reported 7 cases with excellent results, 8 cases with good
      and 15 cases with poor. All cases were statistically analyzed, revealing a
      significant difference (P<0.001) between the two groups. CONCLUSION: The
      displacement of inter-vertebral disks and/or vertebra in the thoracic or lumbar
      region seems to be a contributing factor in the symptoms of irritable bowel
      syndrome. Thumb pressing manipulation on jiaji points in the thoracic and/or
      lumbar region can correct the displacement of inter-vertebral disks and/or
      vertebra, resolving the stimuli caused by pressure exerted on the nerves and
      vessels around the spine. So it is an effective treatment for IBS.

PMID- 24280470
TI  - Acute improvement in hemodynamic control after osteopathic manipulative treatment
      in the third trimester of pregnancy.
AB  - OBJECTIVES: The physiological changes that occur during pregnancy, including
      increased blood volume and cardiac output, can affect hemodynamic control, most
      profoundly with positional changes that affect venous return to the heart. By
      using Osteopathic Manipulative Treatment (OMT), a body-based modality theorized
      to affect somatic structures related to nervous and circulatory systems, we
      hypothesized that OMT acutely improves both autonomic and hemodynamic control
      during head-up tilt and heel raise in women at 30 weeks gestation. DESIGN: One
      hundred subjects were recruited at 30 weeks gestation. SETTING: The obstetric
      clinics of UNTHealth in Fort Worth, TX. INTERVENTION: Subjects were randomized
      into one of three treatment groups: OMT, placebo ultrasound, or time control.
      Ninety subjects had complete data (N=25, 31 and 34 in each group respectively).
      MAIN OUTCOME MEASURES: Blood pressure and heart rate were recorded during 5 min
      of head-up tilt followed by 4 min of intermittent heel raising. RESULTS: No
      significant differences in blood pressure, heart rate or heart rate variability
      were observed between groups with tilt before or after treatment (p>0.36), and
      heart rate variability was not different between treatment groups (p>0.55).
      However, blood pressure increased significantly (p=0.02) and heart rate decreased
      (p<0.01) during heel raise after OMT compared to placebo or time control.
      CONCLUSIONS: These data suggest that OMT can acutely improve hemodynamic control
      during engagement of the skeletal muscle pump and this was most likely due to
      improvement of structural restrictions to venous return.

PMID- 24280471
TI  - Effect of Spiritist "passe" (Spiritual healing) on growth of bacterial cultures.
AB  - BACKGROUND: Biofield therapies are approaches that harness energy fields to
      influence the human body. These therapies encompass Reiki, Qigong, Therapeutic
      Touch, Johrei and Spiritist "passe", among others. The aim of this study was to
      evaluate bacterial growth in two groups of cultures subjected to biofield therapy
      (Spiritist "passe" and laying on of hands (LOH)) in four situations (no
      intention, intention to inhibit bacterial growth, intention to promote growth,
      and influence of a negative factor) and compare them with a "no LOH/no treatment"
      group. METHODS: Bacterial cultures (Escherichia coli ATCC) were randomized and
      allocated into three groups: Spiritist "passe", "LOH", and "no LOH". Bacterial
      growth was assessed using the McFarland Nephelometer Scale. A One-way ANOVA was
      performed to determine group differences in bacterial growth at 48h, and at 1
      week after each situation. RESULTS: A total of 11 Spiritist "passe" healers, 10
      LOH laymen and "no LOH" tubes were assessed. Under the intention to inhibit
      bacterial growth condition, statistically significant differences were found
      between the Spiritist "passe" and "no LOH" Groups (p=0.002 after 48h, and p=0.008
      after one week) and also between the Spiritist "passe" and "LOH" Groups (p=0.005
      after 48h, and p=0.009 after one week). No statistically significant difference
      was detected for the other situations tested (no intention, intention to promote
      growth and influence of a negative factor). CONCLUSIONS: We concluded that
      Spiritist "passe" effectively inhibited growth in bacterial cultures compared to
      LOH with intention or no LOH. Further studies comparing different intentions and
      types of LOH in cultures of cells and microorganisms are warranted.

PMID- 24280472
TI  - Development of a valid and reliable blood stasis questionnaire and its
      relationship to heart rate variability.
AB  - OBJECTIVES: The present study was conducted to develop a valid and reliable Blood
      stasis questionnaire (BSQ), to define its optimum cut-off score, and to examine
      whether the BSQ score affected cardiovascular autonomic function. METHODS: Three
      hundred and thirty-eight outpatients (group A) and 61 inpatients (group B) were
      asked to complete the BSQ. In addition to the BSQ, heart rate variability
      parameters were recorded for group A. We estimated the internal consistency and
      construct validity for the BSQ data from group A. Three clinicians determined
      whether 61 inpatients (group B) exhibited blood stasis (BS), and we defined the
      optimum cut-off point for the BSQ using the clinicians' diagnoses and BSQ scores
      for group B. Finally, the differences in the HRV parameters between the BS and
      non-BS groups (group A) were examined. RESULTS: The 12-item BSQ exhibited a
      satisfactory internal consistency (alpha=0.813). In the test of construct
      validity, a total of three factors (pain-lump, dark blue signs, and trauma) were
      extracted (total percentage of variance=54.8%). ROC curve analyses showed that
      the BSQ had a high discriminative ability for BS (AUC=0.948, 95% confidence
      interval 0.895-1.001). The optimum cut-off score for the BSQ was defined as three
      points. SDNN, TP, LF, and HF were lower in the BS group than in the non-BS group,
      indicating that the BS pattern partially caused a decrease in sympathetic and
      parasympathetic activities. CONCLUSIONS: Our results suggest that the BSQ is a
      valid and reliable instrument for evaluating BS and BS may partially cause a
      decrease in cardiovascular autonomic function.

PMID- 24280473
TI  - A validation study on the insertion depth ranges of the five phase points by
      using musculoskeletal ultrasound: a pilot study.
AB  - OBJECTIVES: We conducted preliminary research to validate the insertion depth
      ranges of the five phase points by using ultrasonography. DESIGN AND SETTING: The
      insertion depth ranges of the five phase points were investigated by reviewing
      acupuncture and moxibustion literature. The following lengths were measured in
      centimetres in order to substitute B-cun values with centimetre values: the
      distance from the cubital crease to the palmar crease, from the inferior border
      of the medial tibia condyle to the medial malleolus, and from the popliteal
      crease to the prominence of the lateral malleolus. The five phase points were
      represented by pen marks on the skin, per the World Health Organization
      acupuncture point specifications. The anatomical structures of the five phase
      points within the insertion depth ranges were observed using colour Doppler
      ultrasound. RESULTS: The five phase points for which the insertion depth ranges
      needed to be modified were LU11, HT9, PC9, LI1, LI2, SI1, SI2, TE1, ST45, BL66,
      GB44, SP1, SP2, LR1, and BL67. The five phase points that required careful
      insertion of acupuncture needles were LU8, LU9, LU10, LI5, ST36, ST41, SP3, HT4,
      HT7, HT8, SI3, SI8, BL40, KI2, KI3, KI10, KI27, GB34, GB38, LR3, and LR4.
      CONCLUSION: This preliminary study provided evidence on the insertion depths in
      acupuncture treatment. To generate more concrete evidence regarding insertion
      depths, further research should be conducted in a participant group with more
      diverse body mass index (BMI) values by using acupoint-specific ultrasonography
      transducers that can measure the acupoints properly.

PMID- 24280474
TI  - Regression analysis of radial artery pulse palpation as a potential tool for
      traditional Chinese medicine training education.
AB  - Pulse palpation was an important part of the traditional Chinese medicine (TCM)
      vascular examination. It is challenging for new physicians to learn to
      differentiate between palpations of various pulse types, due to limited
      comparative learning time with established masters, and so normally it takes many
      years to master the art. The purpose of this study was to introduce an offline
      TCM skill evaluation and comparison system that makes available learning of
      palpation without the master's presence. We record patient's radial artery pulse
      using an existing pressure-based pulse acquisition system, then annotate it with
      teachers' evaluation when palpating the same patient, assigned as likelihood of
      it being each pulse type, e.g. wiry, slippery, hesitant. These training data were
      separated into per-doctor and per-skill databases for evaluation and comparison
      purposes, using the following novel procedure: each database was used as training
      data to a panel of time-series data-mining algorithms, driven by two validation
      tests, with the created training models evaluated in mean-squared-error. Each
      validation of the panel and training data yielded an array of error terms, and we
      chose one to quantitatively evaluate palpation techniques, giving way to compute
      self consistency and mutual-similarity across different practitioners and
      techniques. Our experiment of two practitioners and 396 per-processing samples
      yielded the following: one of the physicians has much higher value of self
      consistency for all tested pulse types. Also, the two physicians have high
      similarity in how they palpate the slipper pulse (P) type, but very dissimilar
      for hesitant (H) type. This system of skill comparisons may be more broadly
      applied in places where supervised learning algorithms can detect and use
      meaningful features in the data; we chose a panel of algorithms previously shown
      to be effective for many time-series types, but specialized algorithms may be
      added to improve feature-specific aspect of evaluation. 

PMID- 24280475
TI  - Psychological, immunological and physiological effects of a Laughing Qigong
      Program (LQP) on adolescents.
AB  - OBJECTIVES: One objective of this study was to assess the effects of laughter on
      the psychological, immunological and physiological systems of the body. Another
      objective was to introduce the Laughing Qigong Program (LQP), as a method of
      standardization for simulated laughter interventions. DESIGN: A randomized,
      prospective, experimental study of the LQP was conducted in a group of
      adolescents (n=67) in Taiwan. During study-hall sessions, experimental subjects
      (n=34) attended the LQP for eight-weeks. Simultaneously, control subjects (n=33)
      read or did their homework. All subjects were tested before and after the
      intervention on the following: Rosenberg Self-Esteem scale (RSE), Chinese Humor
      Scale (CHS) and Face Scale (FS) as psychological markers; saliva cortisol (CS) as
      an immunological marker; blood pressure (BP), heart rate (HR), and heart rate
      variability (HRV) as physiological markers of the body's response to stress. Mood
      states (FS) were measured before/after each LQP session. RESULTS: Mood states
      (p=.00) and humor (p=.004; p=.003) improved in the experimental group; no
      significant changes were found in the controls (p=69; p=60). The immunological
      marker of stress, cortisol levels, decreased significantly for those who
      participated in the LQP (p=.001), suggesting lower levels of stress after
      completion of the program. CONCLUSIONS: The LQP is a non-pharmacological and cost
      effective means to help adolescents mitigate stresses in their everyday life.

PMID- 24280476
TI  - Physiotherapy as one column of an integrative and interdisciplinary medical
      approach--impact of the introduction of diagnosis related groups in Germany.
AB  - OBJECTIVES: To investigate the introduction of case tariff fee remuneration - as
      required by the current system - and its influence on patient satisfaction with
      the provision of physiotherapeutic treatment in an acute hospital aligned on a
      holistic, interdisciplinary therapeutic approach. DESIGN AND SETTING: Randomised
      controlled study with a total of 4598 patients were interviewed. No case tariff
      fee system was used during the years 2004 to 2006. The data were compared with
      the results of interviews that took place during 2007 and 2008 (use of DRGs). The
      results of this study are based on the largest survey performed to date of
      patient satisfaction with physiotherapeutic treatment in acute care focusing on a
      holistic interdisciplinary approach. In-patients being treated under DRG
      conditions were compared with a control group for whom the DRG system had not
      been applied. OUTCOME MEASURES: The target parameter of the study, which took
      more than five years, was the determination of patient satisfaction with the
      physiotherapeutic interventions. RESULTS: There were no significant differences
      between the two groups in respect of satisfaction with the physiotherapeutic
      treatments received. Regarding the outcome parameter encouragement to take more
      exercise, a significant change could be demonstrated under DRG conditions.
      CONCLUSIONS: Physiotherapeutic interventions play an important role in the
      provision of interdisciplinary care. In particular, the holistic perception of
      the patient, the interdisciplinary approach to complex diseases, and the
      requirements of the DRG system on the care provider can exert a positive
      influence on outcome quality.

PMID- 24280477
TI  - Patients with anorexia nervosa receiving acupuncture or acupressure; their view
      of the therapeutic encounter.
AB  - BACKGROUND: Anorexia nervosa is a serious illness with significant morbidity. The
      evidence base for existing psychological and pharmacological interventions to
      manage anorexia nervosa is not strong, and use of new adjunctive therapies that
      improve the effectiveness of existing treatments, and lead to improved mental
      health outcomes for this patient group is highly desirable. This study
      investigates the views of patients with anorexia nervosa receiving an acupuncture
      or acupressure intervention. METHOD: A randomised controlled trial was conducted
      in Sydney, Australia. Twenty-six inpatients with a diagnosis of anorexia nervosa
      were randomised to a six week intervention of acupuncture or acupressure with
      light massage. Treatment was administered twice weekly for three weeks, then
      weekly for three weeks. A post treatment questionnaire was administered to
      explore participant views, of the study consultation. Questions examined
      important aspects of the clinical encounter including the, patient's perception
      of the practitioners' relational empathy (CARE), treatment perceptions and the,
      therapeutic relationship. RESULTS: Participants in both groups scored highly on
      the CARE scale assessing empathy and the, therapeutic relationship. There was no
      difference in the mean CARE scores for the acupuncture group (50 (SD 0.0)) and
      the acupressure group (49.5 (SD 0.8)). Participants highly valued the
      therapeutic, encounter and in particular the characteristics of empathy, positive
      regard, acceptance, non, judgmental responses and trust. Having someone to talk
      to, being less stressed/relaxed and contact, with the study staff were also
      perceived to be important. CONCLUSION: Study participants perceive the
      therapeutic relationship and empathy as important qualities of the acupuncture or
      acupressure intervention as an adjunct therapy for the treatment of anorexia
      nervosa.

PMID- 24280478
TI  - Effects of group music intervention on psychiatric symptoms and depression in
      patient with schizophrenia.
AB  - OBJECTIVES: To examine the effects of a group music therapy on psychiatric
      symptoms and depression for patient with schizophrenia in a psychiatric nursing
      home. SUBJECTS AND METHODS: Eighty patients with schizophrenia were randomly
      assigned to a music intervention group (MIG) or usual care group (UCG). Both
      groups received similar medical and routine care. The MIG received a 60-min group
      music therapy twice a week, a total of ten sessions. The UAG only received the
      usual care with no music therapy. Psychiatric symptoms and depression assessments
      were conducted using the positive and negative syndrome scale and the depression
      scale for schizophrenia at baseline, the posttest, and at a 3-month follow-up.
      RESULTS: Thirty-eight patients in the MIG and 42 in the UCG completed the study.
      After 10 sessions of group music therapy, the groups showed statistically
      significant differences in psychiatric symptoms (p<.05) and depression status
      (p<.05). CONCLUSION: Group music therapy is an economical and easily implemented
      method of improving depression and psychiatric symptoms in patients with
      schizophrenia.

PMID- 24280479
TI  - Effects of music therapy on pain and anxiety in patients undergoing port catheter
      placement procedure.
AB  - BACKGROUND: Patients scheduled to invasive medical procedures experience high
      levels of anxiety, which may lead to increased perceptions of pain and vital sign
      instability throughout. AIMS: To examine the effect of a music intervention (MI)
      on stress hormones, physiologic parameters, pain, and anxiety state before and
      during port catheter placement procedures (PCPPs). METHODS: We conducted a
      prospective, randomized, controlled study in 100 oncology patients, who were
      randomly assigned to an MI group (n=50) or a control group (n=50). The effects of
      music were assessed by determination of serum cortisol and adrenocorticotropic
      hormone (ACTH) levels, heart and respiratory rate (HR, RR) and systolic and
      diastolic blood pressure (SBP, DBP), on arrival in the surgical intervention
      room, as well as immediately prior to and immediately after the PCPP, in both
      groups. Furthermore, pain and anxiety levels were identified using visual
      analogue scale and state-trait anxiety inventory scales. RESULTS: On arrival,
      there were no differences between the patients in terms of serum cortisol and
      ACTH levels, HR, RR, SBP, DBP and anxiety levels. There were significant
      reductions in hormone levels (p<0.05 for all), HR (p<0.001), RR (p<0.001), SBP
      (p<0.05) and DBP (p<0.05), immediately prior to and immediately after the PCPP in
      participants in the MI group compared to those in the control group. Furthermore,
      music led to a significant reduction in pain (p<0.05) and anxiety scores (p<0.05)
      in the MI group compared to control group. CONCLUSION: During invasive medical
      procedures, MI significantly decreases stress hormone levels, physiological
      parameters, acute procedural pain and anxiety.

PMID- 24280480
TI  - Systematic review of the efficacy of pre-surgical mind-body based therapies on
      post-operative outcome measures.
AB  - OBJECTIVES: A large body of research has demonstrated that patient factors are
      strong predictors of recovery from surgery. Mind-body therapies are increasingly
      targeted at pre-operative psychological factors. The objective of this paper was
      to evaluate the efficacy of pre-operative mind-body based interventions on post
      operative outcome measures amongst elective surgical patients. METHODS: A
      systematic review of the published literature was conducted using the electronic
      databases MEDLINE, CINAHL and PsychINFO. Randomised controlled trials (RCTs) with
      a prospective before-after surgery design were included. RESULTS: Twenty studies
      involving 1297 patients were included. Mind-body therapies were categorised into
      relaxation, guided imagery and hypnotic interventions. The majority of studies
      did not adequately account for the risk of bias thus undermining the quality of
      the evidence. Relaxation was assessed in eight studies, with partial support for
      improvements in psychological well-being measures, and a lack of evidence for
      beneficial effects for analgesic intake and length of hospital stay. Guided
      imagery was examined in eight studies, with strong evidence for improvements in
      psychological well-being measures and moderate support for the efficacy of
      reducing analgesic intake. Hypnosis was investigated in four studies, with
      partial support for improvements in psychological well-being measures. Evidence
      for the effect of mind-body therapies on physiological indices was limited, with
      minimal effects on vital signs, and inconsistent changes in endocrine measures
      reported. CONCLUSIONS: This review demonstrated that the quality of evidence for
      the efficacy of mind-body therapies for improving post-surgical outcomes is
      limited. Recommendations have been made for future RCTs.

PMID- 24280481
TI  - Probiotic bacteria in cancer patients undergoing chemotherapy and radiation
      therapy.
AB  - BACKGROUND: Probiotics are live microorganisms, which as drugs or food
      supplements help to maintain health beneficial microbial balance in the digestive
      tract of a human or other host. Probiotics by their properties may help
      strengthen homeostasis and thus reduce side effects associated with cancer
      treatment. Experimental evidence suggests that probiotics might have beneficial
      effect on the toxicity of anticancer therapy. METHODS: A computer-based
      literature search was carried out using PubMed (keywords: "probiotic" and "lactic
      acid bacteria" in association with the search terms "cancer" or "oncology" or
      "chemotherapy" or "radiation"); data reported at international meetings were
      included. RESULTS: Probiotics might have beneficial effects on some aspects of
      toxicity related to anticancer treatment especially radiation therapy. However,
      reported trials vary in utilized probiotic strains, dose of probiotics and vast
      majority of them are small trials with substantial risk of bias. Despite limited
      data, it seems that probiotic bacteria as live microorganisms could be safely
      administered even in the setting of neutropenia. CONCLUSIONS: Current evidence
      supporting probiotic use as adjunctive therapy to anticancer treatment is
      limited, especially in cancer patients treated with chemotherapy. Well designed
      clinical trials are needed to find true role of probiotics in oncology.

PMID- 24280482
TI  - A critical scoping review of external uses of comfrey (Symphytum spp.).
AB  - BACKGROUND: External preparations of the herb comfrey (most commonly Symphytum
      officinale L.) are widely available for over-the-counter, practitioner and
      healthcare professional usage. Traditional practice suggests comfrey can be used
      to treat musculoskeletal disorders, wounds and various other conditions; however
      a full and critical coverage of the evidence base has not yet been undertaken.
      METHODS: A critical scoping review was undertaken. Six bibliographic databases,
      10 grey literature databases and nine trials registers were searched plus
      reference lists of included studies and a descriptive overview of comfrey.
      Randomised or non-randomised clinical trials assessing the external use of
      comfrey for any indication were included and methodological and reporting quality
      were assessed. Observational studies were included only in the assessment of
      adverse events. Studies were grouped and summarised according to the type of
      indication treated. RESULTS: Of 1348 identified records, 64 full texts were
      screened for inclusion and 26 were included in the review - 13 RCTs, 5 non
      randomised controlled trials and 8 observational studies evaluating treatments
      for ankle distortion, back pain, abrasion wounds, venous leg ulcers and
      osteoarthritis. The majority of included trials had an overall unclear risk of
      bias due to poor quality of reporting. Few adverse events were reported.
      CONCLUSIONS: Individual clinical trials showed evidence of benefit for ankle
      distortion, back pain, abrasion wounds and osteoarthritis. Topical application
      appears to be safe but further rigorous assessment is needed. Systematic reviews
      focussing on particular indications may clarify the treatment effect and safety
      of external comfrey preparations.

PMID- 24280483
TI  - Are the CAM professions engaging in high-level health and medical research?
      Trends in publicly funded complementary medicine research grants in Australia.
AB  - INTRODUCTION: Developing research capacity is an essential part of professional
      development in the health professions, as well as essential to improving health
      care delivery. CAM is one area in which the importance of research capacity has
      been previously highlighted. METHODS: To determine whether academic and research
      CAM practitioners were actively engaged in high-level CAM research in Australia
      successful National Health and Medical Research Council grants data for projects
      starting between 2000 to present (2013) were collated and analyzed. RESULTS: CAM
      practitioners are not involved in most NHMRC-funded research, with non-clinical
      academics leading nearly half of all NHMRC-funded CAM grants. Conventional
      medical practitioners led the majority of CAM grants headed by clinicians. Only
      Chinese medicine and naturopathy practitioners appear to be building capacity,
      with NHMRC-funded CAM grants led by these practitioner groups increasing.
      University CAM faculties are for the most part not engaging in high level
      research, with most NHMRC-funded CAM projects being led by groups outside these
      faculties. Even the majority NHMRC-funded research led by CAM clinicians is
      administered outside university CAM faculties. CONCLUSIONS: The CAM professions
      have a low level of engagement with high-level health and medical research in
      Australia. Current levels of engagement appear to be dependent more on individual
      clinician involvement rather than professional strategy. Failure to engage with
      high-level health and medical research may pose challenges for the CAM
      professions, unless research engagement is improved. This requires an active and
      concerted effort from within CAM ranks to build research capacity in the CAM
      professions.

PMID- 24280484
TI  - A dynamic network model of the similia principle.
AB  - The use of drugs in high dilutions and the principle of similarity (or "similia")
      are two basic tenets of homeopathy. However, the plausibility of both is a
      subject of debate. Although several models have been proposed to explain the
      similia principle, it can be best understood and appreciated in the framework of
      complexity science and dynamic systems theory. This work applies a five-node
      Boolean network to show how self-organization and adaptation are relevant to
      rationalizing this traditional medical principle. Simulating the trajectories and
      attractors of the network system in the energy state-space provides a rudimentary
      and qualitative illustration of how targeted external perturbations can have
      pathological effects, leading to permanent, self-sustaining alterations.
      Similarly, changes that conversely enable the system to find its way back to the
      original state can induce therapeutic effects, by causing specific shifts in
      attractors when suitable conditions are satisfied. Extrapolating these mechanisms
      to homeopathy, we can envisage how major changes in the evolution of homeodynamic
      systems (and, eventually, healing of the entire body) can be achieved through
      carefully selected remedies that reproduce the whole symptom pattern of the ill
      state. 

PMID- 24280486
TI  - Resuscitation and rapid response systems.

PMID- 24280485
TI  - Hexokinase-2-mediated aerobic glycolysis is integral to cerebellar neurogenesis
      and pathogenesis of medulloblastoma.
AB  - BACKGROUND: While aerobic glycolysis is linked to unconstrained proliferation in
      cancer, less is known about its physiological role. Why this metabolic program
      that promotes tumor growth is preserved in the genome has thus been unresolved.
      We tested the hypothesis that aerobic glycolysis derives from developmental
      processes that regulate rapid proliferation. METHODS: We performed an integrated
      analysis of metabolism and gene expression in cerebellar granule neuron
      progenitors (CGNPs) with and without Sonic Hedgehog (Shh), their endogenous
      mitogen. Because our analysis highlighted Hexokinase-2 (Hk2) as a key metabolic
      regulator induced by Shh, we studied the effect of conditional genetic Hk2
      deletion in CGNP development. We then crossed Hk2 conditional knockout mice with
      transgenic SmoM2 mice that develop spontaneous medulloblastoma and determined
      changes in SmoM2-driven tumorigenesis. RESULTS: We show that Shh and
      phosphoinositide 3-kinase (PI3K) signaling combine to induce an Hk2-dependent
      glycolytic phenotype in CGNPs. This phenotype is recapitulated in
      medulloblastoma, a malignant tumor of CGNP origin. Importantly, cre-mediated
      ablation of Hk2 abrogated aerobic glycolysis, disrupting CGNP development and
      Smoothened-induced tumorigenesis. Comparing tumorigenesis in medulloblastoma
      prone SmoM2 mice with and without functional Hk2, we demonstrate that loss of
      aerobic glycolysis reduces the aggressiveness of medulloblastoma, causing tumors
      to grow as indolent lesions and allowing long-term survival of tumor bearing
      mice. CONCLUSIONS: Our investigations demonstrate that aerobic glycolysis in
      cancer derives from developmental mechanisms that persist in tumorigenesis.
      Moreover, we demonstrate in a primary tumor model the anti-cancer potential of
      blocking aerobic glycolysis by targeting Hk2.See commentary
      article:http://www.biomedcentral.com/1741-7007/11/3.

PMID- 24280487
TI  - Use of pheromone timed insecticide applications integrated with mating disruption
      or mass trapping against Ostrinia furnacalis (Lepidoptera: Pyralidae) in sweet
      corn.
AB  - Mating disruption and mass trapping of Ostrinia furnacalis (Genuee), often called
      the Asian corn borer, were incorporated with insecticides to reduce pesticide
      use. Pesticides alone are often ineffective owing to problems in timing
      applications before the larvae enter the protection of corn stalks. In addition,
      overuse of insecticides has caused environmental contamination and concerns about
      consumer health. In 2010, 15 insecticides were compared with mating disruption or
      mass trapping at various dispenser (disp.) densities for reducing egg masses,
      trap captures, and ear damage. Mass trapping with 30 and 40 disp./ha, mating
      disruption with 300 disp./ha, or endosulfan, chlorpyrifos, and monosultap (0.55,
      0.35, and 0.55 kg/ha, respectively) gave ?50% ear protection. In 2011, an
      insecticide alone, no treatments, pheromone alone, and pheromone + insecticide
      were examined. The same insecticides in combination with mating disruption or
      mass trapping at ?200 or?20 disp./ha gave >90% ear protection even when chemical
      applications were reduced to 1 from 3, and the rates were reduced 50-75%.
      Pheromone dispensers contained >50% of their initial load 30 d after exposure. 

PMID- 24280488
TI  - [Implementation of a third national cancer plan in France].

PMID- 24280489
TI  - [Post-translational diversification of immunoglobulins specificity].

PMID- 24280490
TI  - [TGFbeta contribution to hematopoietic regeneration after myelosuppressive
      chemotherapy].

PMID- 24280491
TI  - [Beating frequency of motile cilia lining the third cerebral ventricle is finely
      tuned by the hypothalamic peptide MCH].

PMID- 24280492
TI  - [Tissue to tissue dialogue and modulation of the Notch pathway control aortic
      haematopoiesis].

PMID- 24280493
TI  - [Pseudomonas aeruginosa caught in the act!].

PMID- 24280494
TI  - [Surviving nutrient deprivation by restraining translation elongation: biological
      function of the eEF2 kinase].

PMID- 24280495
TI  - [Crosstalk between the liver and the gut: role of the microbiota in liver
      carcinogenesis].

PMID- 24280496
TI  - [Video games as a therapeutic approach for patients: coming soon?].

PMID- 24280497
TI  - [Role of microvesicles in malaria infections].

PMID- 24280498
TI  - [Sensual choreography: coordinated migration of cephalic sensory precursors].

PMID- 24280499
TI  - [Sickle-cell disease: geographical distribution and population estimates].

PMID- 24280500
TI  - [The inflammasomes: platforms of innate immunity].
AB  - Human beings are constantly exposed to pathogens. The innate immune system is the
      first line of defense against microbes. It has evolved to recognize conserved
      microbial motifs (PAMP or pathogen-associated molecular patterns) thanks to a
      limited array of receptors termed pattern recognition receptors (PRR). Upon
      activation, most PRR trigger a transcriptional response leading to neosynthesis
      of hundreds of genes. In contrast, engagement of various PRR in the recently
      identified inflammasome complexes lead to activation of a cysteine protease,
      caspase-1. This inflammatory caspase has a dual activity: it triggers the release
      of very potent proinflammatory cytokines IL-1beta and IL-18 and, an
      hyperinflammatory cell death termed pyroptosis. In this review, we describe the
      inflammasome receptors and their ligands, the molecular mechanisms leading to the
      assembly of this innate immune platform and the role of the inflammasome during
      viral and bacterial infections.

PMID- 24280501
TI  - [Control of innate immune system for cancer therapy].
AB  - Immunotherapies are particularly attractive when one wants to fight cancer since
      they aim at controlling the immune system in order to eradicate cancer cells and
      prevent tumor dissemination. While the clinical use of specific ligands for the
      innate immune receptors is promising, it is still facing several drawbacks when
      entering clinical trials. Nevertheless, recent advances in our understanding of
      the biology of these receptors constrain us to re-assess existing strategies and
      let foresee new approaches in the pipeline of therapies that would overcome
      current limitations. 

PMID- 24280502
TI  - [Kras oncogene and pancreatic cancer: thirty years after].
AB  - Point mutations of the Kras oncogene induce in cancerous cells an uncontrolled
      increase of cell proliferation and invasiveness. Mutation of Kras appears early
      during the process of the pancreatic carcinogenesis and is the most frequent
      genetic alteration in pancreatic adenocarcinoma (75 to 95 % of cases) as well as
      in precancerous lesions such as PanIN and IMPN. These latter lesions and tumour
      microenvironment are reproduced in transgenic models developed in mice. These
      models are induced on the basis of Kras mutation (Pdx1-Cre ; Kras(G12D) mice)
      associated or not to the inactivation of tumour suppressor genes (TP53, DPC4,
      INK4A). Kras mutation assay is easily performed in human biological samples,
      especially in the cellular material sampled in pancreatic masses under endoscopic
      ultrasound by fine needle aspiration biopsy. In the near future, searching for
      Kras mutation could be useful in clinical practice either for positive diagnosis
      of pancreatic adenocarcinoma in case of unconclusive/doubtful cytopathological
      analysis or for the differential diagnosis with chronic pancreatitis especially
      in its pseudotumoural form. 

PMID- 24280503
TI  - [Hepatitis C virus: 25 years-old, the end?].
AB  - The treatment of hepatitis C virus (HCV) infection markedly progressed these two
      last decades. Since 15 years, the combination of pegylated interferon alpha and
      ribavirin led to a sustained virologic response (SVR) which corresponds to a
      complete recovery in around 45 % of patients with HCV genotype 1, 65 % with HCV
      genotype 4, 70 % with HCV genotype 3 and around 85 % with HCV genotype 2. A
      better understanding of the HCV life-cycle recently resulted in the development
      of several potential direct-acting antiviral drugs (DAA) targeting viral proteins
      (NS3/4A protease inhibitors, NS5B nucleosidic and non nucleosidic polymerase
      inhibitors, NS5A replication complex inhibitors). A lot of data has been reported
      with the combinations of pegylated interferon alpha/ribavirin and the first
      generation oral DAA, Telaprevir and Boceprevir. These regimens have demonstrated
      a high level of antiviral efficacy (75 % of SVR) and an acceptable safety
      profile. After this first major step, the combination of the second generation
      DAA with pegylated interferon alpha/ribavirin will impact antiviral potency (75
      to 90 % of SVR) and tolerance and will reduce the duration of therapies and the
      pill burden. The next step, which is an actual revolution, will be the oral
      combination of new DAA which is likely to become the standard of care for chronic
      HCV after 2015. Most studies have been conducted in small numbers of "easy-to
      treat" patients with short post-treatment period with outstanding results but we
      are now waiting for confirming these results in more difficult-to-treat patients
      (experienced genotype 3-infected or genotype 1-infected patients who failed to
      first generation protease inhibitors, cirrhotic, HIV co-infected patients,
      allograft recipients or candidates to transplantation). 

PMID- 24280504
TI  - [Phagocytosis and cytokinesis: highlights on common themes and differences].
AB  - Eukaryotic cells use and adapt common molecular machineries. Recent findings have
      highlighted that actin polymerization, contractile activity and membrane
      remodelling with exocytosis of internal compartments are required both for
      successful phagocytosis, the internalization of particulate material and for
      cytokinesis, the last step of cell division. Phagocytosis is induced by the
      triggering of specific cell surface receptors, which leads to membrane
      deformation, pseudopod extension and contraction to engulf particles. Cytokinesis
      relies on intense contractile activity and eventually leads to the physical
      scission of sister cells. In this review, shared features of signalling,
      cytoskeletal reorganization and vesicular trafficking used in both phagocytosis
      and cytokinesis are described, and questions that remain open in these dynamic
      areas of research are also highlighted. 

PMID- 24280505
TI  - [miR-9: a key factor of the physiopathological regulation of the neural
      progenitor state].
AB  - microRNA are small non-coding RNA that modulate gene expression post
      transcriptionally. Discovered 20 years ago, their individual functions start to
      be unraveled. Collectively, functional studies point to an important functional
      plasticity of microRNA, along the course of evolution, and across different
      cellular contexts. This is the case in particular for one of them, miR-9, a key
      factor of the regulation of the neural progenitor state in Vertebrates. 

PMID- 24280506
TI  - [SIBLING proteins: molecular tools for tumor progression and angiogenesis].
AB  - The small integrin-binding ligand N-linked glycoprotein (SIBLING) family consists
      of osteopontin (OPN), bonesialoprotein (BSP), dentin matrix protein 1 (DMP1),
      dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein
      (MEPE). These proteins, initially identified in bone and teeth, share many
      structural characteristics. It is now well established that they are over
      expressed in many tumors and play a critical role at different steps of cancer
      development. In this review, we describe the roles of SIBLING proteins at
      different stages of cancer progression including cancer cell adhesion,
      proliferation, migration, invasion, metastasis and angiogenesis. 

PMID- 24280507
TI  - [The Warburg effect: from theory to therapeutic applications in cancer].
AB  - Cancer cell metabolism described by Otto Warburg in the thirties became a cancer
      specific hallmark, also called "Warburg effect". Cancer cells use essentially
      glucose as fuel, through glycolysis, in order to meet their energy and biomass
      needs to insure their cell proliferation. Recent advances describe Warburg effect
      regulation by oncogenes and tumor suppressor genes. Moreover, mutations in some
      glycolysis enzymes are found in various cancers, highlighting the role of cell
      metabolism in cancer. In this review, we describe the mechanisms responsible for
      the Warburg effect at the molecular and cellular level, the role of cell
      signalling along with the implication of different transcription factors. As a
      cause or a consequence of tumorigenesis, the Warburg effect is now considered as
      a promising therapeutic target in the fight against cancer. 

PMID- 24280508
TI  - [Eradication of poliomyelitis and emergence of pathogenic vaccine-derived
      polioviruses: from Madagascar to Cameroon].
AB  - The oral poliovaccine, a live vaccine made of attenuated poliovirus strains, is
      the main tool of the vaccination campaigns organised for eradicating
      poliomyelitis. these campaigns had led to the decline and, thereafter, to the
      disappearance of wild poliovirus strains of the three serotypes (1-3) in most
      parts of the world. However, when the poliovaccine coverage becomes too low,
      vaccine polioviruses can circulate in insufficiently immunized populations and
      become then pathogenic by mutations and genetic recombination with other
      enteroviruses of the same species, in particular some coxsackievirus A. These
      mutated and recombinant vaccine strains have been implicated in several epidemics
      of paralytic poliomyelitis. Two polio outbreaks associated with these pathogenic
      circulating vaccine-derived poliovirus (cVDPV) occurred in 2001-2002 and 2005 in
      the South of Madagascar where vaccine coverage was low. These cVDPV, of serotype
      2 or 3, were isolated from paralyzed children and some of their healthy contacts.
      Other cVDPV were isolated in the same region from healthy children in 2011,
      indicating that these viruses were circulating again. Vaccination campaigns could
      stop the outbreaks in 2002 and 2005, and most probably prevent another one in
      2011. Therefore, the genetic plasticity of poliovaccine strains that threatens
      the benefit of vaccination campaigns is the target of an accurate surveillance
      and an important theme of studies in the virology laboratories of the Institut
      Pasteur international network. 

PMID- 24280509
TI  - [Combined behavioural and neuroscientific insights can improve anti-tobacco
      strategies].
AB  - In France, cognitive science (e.g., eye-tracking) and neuroscience (e.g.,
      functional neuroimaging) are not used to develop and test anti-tobacco
      strategies. The newly found knowledge in behavioral and brain sciences could
      provide valuable insights in the understanding of attentional, emotional,
      memorization and decision-making processes at play when tobacco addicts are
      exposed to prevention messages. We argue that neuroscientific methods should be
      used in the fight against tobacco to better design and evaluate the impact of
      measures such as combined text and graphic (shock) warnings, neutral packets and
      support to people who want to stop smoking. 

PMID- 24280510
TI  - [Lessons from the HeLa story].
AB  - An exceptional arrangement concluded for access to the HeLa cell line sequence
      highlights the problems involved in studies on " old " samples obtained before
      ethical and privacy safeguards were in place.

PMID- 24280511
TI  - [Nobel Prize in Physiology and Medicine 2013 - an award for the discovery of the
      actors and fundamental molecular mechanisms of intracellular vesicle
      trafficking].

PMID- 24280512
TI  - Remote ischemic preconditioning with--but not without--metabolic support protects
      the neonatal porcine heart against ischemia-reperfusion injury.
AB  - BACKGROUND: While remote ischemic preconditioning (rIPC) protects the mature
      heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart
      is not known. The neonatal heart relies almost solely on carbohydrate metabolism,
      which is modified by rIPC in the mature heart. We hypothesized that rIPC combined
      with metabolic support with glucose-insulin (GI) infusion improves cardiac
      function and reduces infarct size after IR injury in neonatal piglets in-vivo.
      METHODS AND RESULTS: 32 newborn piglets were randomized into 4 groups: control,
      GI, GI+rIPC and rIPC. GI and GI+rIPC groups received GI infusion continuously
      from 40 min prior to ischemia. rIPC and GI+rIPC groups underwent four cycles of 5
      min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the
      left anterior descending artery followed by 2 h reperfusion. Myocardial lactate
      concentrations were assessed in microdialysis samples analyzed by mass
      spectrometry. Infarct size was measured using triphenyltetrazolium chloride
      staining. Systolic recovery (dP/dt(max) as % of baseline) after 2 h reperfusion
      was 68.5+/-13.8% in control, 53.7+/-11.2% in rIPC (p<0.05), and improved in GI
      (83.6+/-18.8%, p<0.05) and GI+rIPC (87.0+/-15.7%, p<0.01). CONCLUSION: rIPC+GI
      protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has
      detrimental metabolic and functional effects that are abrogated by simultaneous
      GI infusion.

PMID- 24280513
TI  - A new PGPR co-inoculated with Bradyrhizobium japonicum enhances soybean
      nodulation.
AB  - A new PGPR (plant growth promoting rhizobacteria) strain was isolated from
      soybean seeds and the bacterial mechanisms related to plant growth promotion were
      evaluated and characterized. Isolates were genotypically compared and identified
      by amplification of partial sequences of 16S DNAr as Bacillus amyloliquefaciens
      strain LL2012. Isolates were grown until exponential growth phase to evaluate the
      atmospheric nitrogen fixation, enzymatic activities, phosphate solubilization,
      siderophores and phytohormones production. LL2012 strain was able to grow and to
      produce high levels of auxin, gibberellins and salicylic acid in chemically
      defined medium. Co-inoculation of soybean plants with LL2012 strain and the
      natural symbiont (Bradyrhizobium japonicum) altered plant growth parameters and
      significantly improved nodulation. Our results show that the association of
      LL2012 with B. japonicum, enhanced the capacity of the latter to colonize plant
      roots and increase the number of nodules, which make the co-inoculation technique
      attractive for use in commercial inoculant formulations following proper field
      evaluation. 

PMID- 24280514
TI  - Imagery and likelihood cognitive bias in pain.
AB  - BACKGROUND: Distressing intrusive images are frequently experienced by sufferers
      from chronic and acute pain. The images (Index images) are correlated with
      elevations in anxiety, threat, and a cognition that the imaged event might
      actually happen. The over-estimation that having a negative cognition about an
      adverse event will increase the probability of the negative event occurring--the
      likelihood bias--has been observed in a variety of psychological disorders.
      Preliminary research indicated this cognitive bias might occur in pain sufferers.
      AIMS: To investigate the occurrence of a cognitive likelihood bias associated
      with imagery in acute and chronic pain sufferers, and to relate the postulated
      cognitive bias to psychological characteristics of participants, and four other
      important cognitive responses to their Index images. METHOD: Fifty-nine pain
      sufferers completed a newly developed questionnaire (Image-Event-Fusion-pain: IEF
      p) to assess cognitive likelihood bias in pain sufferers. The internal
      consistency, reliability, factor structure and validity of the scale were
      evaluated. Psychological measures to assess anxiety, depression, PTSD symptoms,
      and levels of mental defeat were administered. RESULTS: The IEF-p was found to be
      psychometrically robust with satisfactory test-retest reliability, good internal
      consistency, single factor structure and criterion validity. The IEF-p was
      significantly correlated with four key cognitive appraisals of the Index Images
      (responsibility, likelihood, premonition, and threat). Three of these
      correlations were independent of depression. High cognitive bias scores were
      significantly associated with elevated levels of anxiety symptoms, depression,
      PTSD symptoms, and mental defeat. CONCLUSION: Pain Index images were
      significantly associated with cognitive bias (IEF-p), increased threat levels,
      and raised estimate of the likelihood of imaged events actually occurring. The
      results indicate the prevalence of a cognitive bias associated with pain imagery
      cognitions, comparable to that established with intrusive cognitions in OCD,
      notably Thought-Action- Fusion.

PMID- 24280517
TI  - Practice guidelines for hypothyroidism in adults: clinical issues and the
      controversy about combination therapy.

PMID- 24280520
TI  - ABO blood groups of residents and the ABO host choice of malaria vectors in
      southern Iran.
AB  - Recent epidemiological evidences revealed the higher prevalence of 'O' blood
      group in the residents of malaria-endemic areas. Also some data indicated
      preference of mosquitoes to 'O' group. The aim of this study was to determine ABO
      group ratio in the residents as well as ABO group preference of Anopheles in two
      malaria endemic areas in south of Iran. Agglutination method was used for ABO
      typing of residents. Field blood fed Anopheles specimens were tested against
      vertebrate DNA using mtDNA-cytB PCR-RFLP and then the human fed specimens were
      tested for ABO groups using multiplex allele-specific PCR. A total of 409 human
      blood samples were identified, of which 150(36.7%) were 'O' group followed by
      113(27.6%), 109(26.7%), and 37(9.0%) of A, B, and AB groups respectively.
      Analyzing of 95 blood fed mosquitoes revealed that only four Anopheles stephensi
      had fed human blood with A(1), B(1), and AB(2) groups. Result of this study
      revealed high prevalence of O group in south of Iran. To our knowledge, it is the
      first ABO molecular typing of blood meal in mosquitoes; however, due to low
      number of human blood fed specimens, ABO host choice of the mosquitoes remains
      unknown. This study revealed that ABO blood preference of malaria vectors and
      other arthropod vectors deserves future research. 

PMID- 24280521
TI  - Amentoflavone inhibits angiogenesis of endothelial cells and stimulates apoptosis
      in hypertrophic scar fibroblasts.
AB  - Amentoflavone (8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7
      dihydroxy-2-(4-hydroxyphenyl) chromen-4-one; AF) is a biflavonoid derived from
      the extracts of Selaginella tamariscina. It has been shown that AF has diverse
      biological effects such as antitumour, etc. It is well known that high cell
      proliferation, viability, angiogenesis and low apoptosis are key factors in
      hypertrophic scar formation. In this study, we report that AF inhibited viability
      and stimulated apoptosis in hypertrophic scar fibroblasts (HSFBs). Incubation of
      HSFBs with AF showed its inhibitory effect on cell viability and the exhibition
      of a series of cellular changes that were consistent with apoptosis. By Western
      blot analysis, our data indicated significant increases in the amounts of cleaved
      caspases 3, 8, 9 and Bax, several apoptotic promoters and a significant decrease
      in translationally controlled tumour protein (TCTP), an apoptotic inhibitor, in
      HSFBs treated with AF. Furthermore, AF showed significant inhibitions on the
      viability, migration and tube formation of endothelial cells, which are
      associated with angiogenesis. In conclusion, this study suggests that AF
      stimulates apoptosis in HSFBs and inhibits angiogenesis of endothelial cells.
      Therefore, AF is a promising molecule that can be used in hypertrophic scar
      treatment. 

PMID- 24280522
TI  - Development of a one-step approach for the reconstruction of full thickness skin
      defects using minced split thickness skin grafts and biodegradable synthetic
      scaffolds as a dermal substitute.
AB  - INTRODUCTION: Tissue engineering has progressed in delivering laboratory-expanded
      keratinocytes to the clinic; however the production of a suitable alternative to
      a skin graft, containing both epidermis and dermis still remains a challenge.
      AIM: To develop a one-step approach to wound reconstruction using finely minced
      split thickness skin and a biodegradable synthetic dermal substitute. METHODS:
      This was explored in vitro using scalpel diced pieces of split thickness human
      skin combined with synthetic electrospun polylactide (PLA) scaffolds. To aid the
      spreading of tissue, 1% methylcellulose was used and platelet releasate was
      examined for its effect on cellular outgrowth from tissue explants. The outcome
      parameters included the metabolic activity of the migrating cells and their
      ability to produce collagen. Cell presence and migration on the scaffolds were
      assessed using fluorescence microscopy and SEM. Cells were identified as
      keratinocytes by immunostaining for pan-cytokeratin. Collagen deposition was
      quantified by using Sirius red. RESULTS: Skin cells migrated along the fibers of
      the scaffold and formed new collagen. 1% methylcellulose improved the tissue
      handling properties of the minced skin. Platelet releasate did not stimulate the
      migration of skin cells along scaffold fibers. Immunohistochemistry and SEM
      confirmed the presence of both epithelial and stromal cells in the new tissue.
      CONCLUSION: We describe the first key steps in the production of a skin
      substitute to be assembled in theatre eliminating the need for cell culture.
      Whilst further experiments are needed to develop this technique it can be a
      useful addition to armamentarium of the reconstructive surgeon.

PMID- 24280523
TI  - Stroke after burn: population data analysis.
AB  - PURPOSE OF THE STUDY: We aimed to describe a population cohort study of burns
      with the prevalence of stroke, and discuss possible etiologies. ANALYTICAL
      METHODS: This study uses data obtained from the Longitudinal Health Insurance
      Database 2005 (LHID2005). The study cohort consisted of all patients who had
      diagnoses of burn recorded in the database (ICD-9-CM codes 948) between January 1
      2004 and December 31 2008 (N=1549). MAIN FINDINGS: The patients with burn and the
      comparison cohort are 7410 patients, 146 experienced stroke during the follow-up
      period of up to 5 years. In average, the burn patients suffered from stroke by
      1.48 years after burn. The hazard ratio of stroke was 1.74 (95% CI, 1.15-2.63)
      for patients with TBSA burn <20%, 3.78 (95% CI, 1.39-10.26) for patients with
      TBSA burn >=20%. The adjusted hazard ratio of ischemic stroke was 1.63 for
      patients with TBSA burn <20%, 2.96 for patients with TBSA burn >=20%, whereas the
      hazard ratio of hemorrhagic stroke were not significant (p=0.231). CONCLUSIONS:
      In our study, severe burned patients, more than 60 years of age, had higher risk
      of stroke in their recovery life. We suggest close follow up for the burn
      patients in high risk of stroke.

PMID- 24280524
TI  - Pyruvate-enriched oral rehydration solution improved intestinal absorption of
      water and sodium during enteral resuscitation in burns.
AB  - AIM: To investigate alteration in intestinal absorption during enteral
      resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in
      scalded rats. METHODS: To compare pyruvate-enriched oral rehydration solution
      (Pyr-ORS) with World Health Organisation oral rehydration solution (WHO-ORS), 120
      rats were randomly divided into 6 groups and 2 subgroups. At 1.5 and 4.5 h after
      a 35% TBSA scald, the intestinal absorption rate, mucosal blood flow (IMBF),
      Na(+)-K(+)-ATPase activity and aquaporin-1 (AQP-1) expression were determined (n
      = 10), respectively. RESULTS: The intestinal Na(+)-K(+)-ATPase activity, AQP-1
      expression and IMBF were markedly decreased in scald groups, but they were
      profoundly preserved by enteral resuscitation with WHO-ORS and further improved
      significantly with Pyr-ORS at both time points. Na(+)-K+-ATPase activities
      remained higher in enteral resuscitation with Pyr-ORS (Group SP) than those with
      WHO-ORS (Group SW) at 4.5 h. AQP-1 and IMBF were significantly greater in Group
      SP than in Group SW at both time points. Intestinal absorption rates of water and
      sodium were obviously inhibited in scald groups; however, rates were also
      significantly preserved in Group SP than in Group SW with an over 20% increment
      at both time points. CONCLUSION: The Pyr-ORS may be superior to the standard WHO
      ORS in the promotion of intestinal absorption of water and sodium during enteral
      resuscitation.

PMID- 24280525
TI  - Hot ash burns in the children of Western Australia: how and why they happen.
AB  - INTRODUCTION: Burns from hot ash are common in the paediatric population in
      Western Australia. Fifty children were admitted to the paediatric burn centre
      with hot ash contact burns to the feet in 2011 and 2012. It is important to
      examine the extent of the problem, seasonal variations, and identify those at
      risk to determine strategies for prevention campaigns. METHOD: Retrospective
      review of medical notes for all admissions to the paediatric burns unit was
      undertaken for 2011 and 2012. Data were collected for patient demographics, time,
      circumstance of injury, burn severity and treatment. RESULTS: Hot ash burns
      accounted for 8.6% of admissions but 16.1% of burns sustained in non-metro areas.
      Median age was just under 3 years, male or female. Median burn TBSA was 2%, and
      44% of children required surgery. The burns were less common in summer, more
      common on non-school days and in children who were on camping trips away from
      home. DISCUSSION: Previous work has shown the value of targeted campaigns. The
      group for targeted prevention campaigns are the carers of very young children who
      go camping. Information distributed at camping shows and stores about the
      principles of campfire safety would reach the people at risk.

PMID- 24280527
TI  - Erosive pustular dermatosis: new description of a possible cause of the non
      healing burn wound.
AB  - INTRODUCTION: Erosive pustular dermatosis (EPD) is a cutaneous condition,
      characterised by sterile pustular lesions, erosions and crusting. Extensive or
      infected disease may result in scarring. EPD has never been reported following
      burn. The aim of this study was to describe the presentation and management of
      EPD complicating burns wounds. METHODS: A consecutive series of EPD cases
      secondary to burn. RESULTS: Six cases were identified. In each case, erosive
      lesions and crusts were located at the site of burn or at the site of split skin
      grafting after tangential burn excision. All cases presented as failure to heal
      or repeated wound breakdown, despite standard burn wound management. Pain was a
      significant feature in all cases. Microbiological cultures demonstrated either
      benign colonising bacteria or no pathogens. Time to EPD diagnosis by the
      interdisciplinary team was 126 +/- 27 days (mean +/- SEM). Topical therapy with
      short course, potent corticosteroids resulted in clinical remission in 15 +/- 2
      days (mean +/- SEM) without clinical relapses after 15 +/- 4 months (mean +/-
      SEM). CONCLUSION: EPD may occur following burns. EPD should be considered in the
      differential diagnosis of a non-healing burn wound and resolves readily with
      topical potent corticosteroid therapy.

PMID- 24280526
TI  - Burns at KCMC: epidemiology, presentation, management and treatment outcome.
AB  - BACKGROUND: About 90% of the global burden of burns occurs in the low and middle
      income countries. In Africa it is estimated that between 17,000 and 30,000
      children under five die each year due to burns. In Tanzania there are no
      specialized burn centers. Burn patients are often managed in the general surgical
      wards in most hospitals. Kilimanjaro Christian Medical Centre is one of the four
      tertiary referral hospitals in Tanzania. RATIONALE: This study aimed to review
      the epidemiology presentation management and outcome of burn patients in this
      challenging environment. PATIENTS AND METHODS: A cross-sectional prospective
      study involving 41 patients was undertaken from October 2011 to April 2012.
      RESULTS: 65.9% were males. The largest age group was below 5 years (36.6%). 19.5%
      were epileptic. More than half of the burns were due to open flame. 80.5% had
      second degree burns. 56.1% had a BSA of 15% or less and 56.1% had an APACHE score
      of 10 or less. It was found that 73.2% of burns occurred at home. The commonest
      prehospital first aid applied was honey. Only 41.5% arrived in hospital within
      the first 24h after burn. Among the 14.6% who had skin grafting, none had early
      excision of burn wound. 53.7% developed wound sepsis while 24.4% developed
      contractures. The mortality rate was 26.8%. CONCLUSION: Children under five are
      the worst affected by burns. Most patients had second degree burn wounds.
      Inappropriate management of the burn wound started just after injury and
      continued even in hospital. Mortality and complication rates are high.

PMID- 24280528
TI  - Site of catheter insertion in burn patients and infection: a systematic review.
AB  - The aim of the study was to conduct a systematic review to identify and appraise
      the evidence on possible association of the site of venous catheter insertion in
      burn patients and an increased occurrence of catheter-related infection. Searches
      were performed in MEDLINE, LILACS, CINAHL, EMBASE, Web of Science and The
      Cochrane Library. Nine studies were selected for the review; four of them
      mentioned, directly or indirectly, an association between catheter-related
      infection and the insertion of the catheter either in the burn wound or in
      surrounding area, and five studies investigated the occurrence of infection
      related to both the catheter and the anatomical sites of catheter insertion.
      Higher infection rates occurred when the catheters were inserted directly in the
      burn wound or near the wound (level of evidence IV) or in the femoral vein (level
      of evidence IV). No significant differences in infection occurrence rates were
      observed between central catheters and peripherally inserted central catheter
      (level of evidence IV). Further investigations for techniques and types of
      coverage of venous catheter insertion dressings are important for preventing
      infection in burn patients. Also, new technologies for venous access must be
      evaluated. 

PMID- 24280529
TI  - Influencing factors of the quality of life in Chinese burn patients:
      Investigation with adapted Chinese version of the BSHS-B.
AB  - OBJECTIVE: The study aims to evaluate the quality of life (QOL) in burn patients
      in China and find out principal influencing factors, so as to provide evidence
      for interventions. METHODS: A total of 271 burn patients in three major burn
      units in China were asked to fill in the adapted Chinese version (ACV) of the
      Burn Specific Health Scale-Brief (ACV BSHS-B) in order to seek out the principal
      influencing factors in combination with a self-designed demographic and disease
      condition questionnaire. Multivariable linear regression was used to analyse the
      principal influencing factors. RESULTS: The findings showed that there were seven
      principal influencing factors for the overall ACV BSHS-B score. They were:
      percent total body surface area (TBSA) burned (with the standardised regression
      coefficient being -0.594), burn area of lower limber (0.241), itch level (
      0.227), pain level (-0.220), gender (0.217), mechanical ventilation (0.216) and
      hand deformity (-0.141). CONCLUSION: QOL decreased in burn patients to different
      degrees depending on the intensity of burns. With a better understanding of
      influencing factors of burn patients' QOL, the medical and nursing staff can take
      specific countermeasures to help patients gain a higher QOL.

PMID- 24280530
TI  - Validation of the Italian version of the burn specific health scale-brief.
AB  - INTRODUCTION: A growing awareness of psychological and functional impairment due
      to burns have led to the development of specific instruments to evaluate Quality
      of Life in this population, such as the Burn Specific Health Scale - Brief (BSHS
      B), whose psychometric properties have been consistently verified. The aim of
      this study was to translate the BSHS-B into Italian and to investigate its
      reliability and validity. METHODS: Translation procedures were carried out
      according to accepted standards. Internal reliability was assessed using
      Cronbach's alpha coefficient. Concurrent validity was evaluated through
      correlations between the BSHS-B and the Short-Form 36 Health Survey (SF-36), the
      Self-report Clinical Inventory (SCL-90), and the Body Uneasiness Test (BUT).
      RESULTS: The overall Cronbach's alpha value for the scale was 0.887. Significant
      correlations were found between the Italian BSHS-B domains, the SF-36 subscales
      (Spearman's rho: 0.184-0.414), and several SCL-90 subscales (Spearman's rho: 
      0.173 to -0.477). Furthermore, the affect and relationship domain and the skin
      domain of the BSHS-B negatively correlated with the compulsive self-monitoring
      and depersonalization subscales of the BUT. CONCLUSION: The Italian translation
      of BSHS-B has shown satisfactory internal consistency, criterion validity, and
      convergent validity, supporting its application in routine clinical practice as
      well as in international studies.

PMID- 24280531
TI  - Computational modeling of direct neuronal recruitment during intracortical
      microstimulation in somatosensory cortex.
AB  - OBJECTIVE: Electrical stimulation of cortical tissue could be used to deliver
      sensory information as part of a neuroprosthetic device, but current control of
      the location, resolution, quality, and intensity of sensations elicited by
      intracortical microstimulation (ICMS) remains inadequate for this purpose. One
      major obstacle to resolving this problem is the poor understanding of the neural
      activity induced by ICMS. Even with new imaging methods, quantifying the activity
      of many individual neurons within cortex is difficult. APPROACH: We used
      computational modeling to examine the response of somatosensory cortex to ICMS.
      We modeled the axonal arbors of eight distinct morphologies of interneurons and
      seven types of pyramidal neurons found in somatosensory cortex and identified
      their responses to extracellular stimulation. We then combined these axonal
      elements to form a multi-layered slab of simulated cortex and investigated the
      patterns of neural activity directly induced by ICMS. Specifically we estimated
      the number, location, and variety of neurons directly recruited by stimulation on
      a single penetrating microelectrode. MAIN RESULTS: The population of neurons
      activated by ICMS was dependent on both stimulation strength and the depth of the
      electrode within cortex. Strikingly, stimulation recruited interneurons and
      pyramidal neurons in very different patterns. Interneurons are primarily
      recruited within a dense, continuous region around the electrode, while pyramidal
      neurons were recruited in a sparse fashion both near the electrode and up to
      several millimeters away. Thus ICMS can lead to an unexpectedly complex spatial
      distribution of firing neurons. SIGNIFICANCE: These results lend new insights to
      the complexity and range of neural activity that can be induced by ICMS. This
      work also suggests mechanisms potentially responsible for the inconsistency and
      unnatural quality of sensations initiated by ICMS. Understanding these mechanisms
      will aid in the design of stimulation that can be used to generate effective
      sensory feedback for neuroprosthetic devices.

PMID- 24280532
TI  - Frames of scientific evidence: How journalists represent the (un)certainty of
      molecular medicine in science television programs.
AB  - For laypeople, media coverage of science on television is a gateway to scientific
      issues. Defining scientific evidence is central to the field of science, but
      there are still questions if news coverage of science represents scientific
      research findings as certain or uncertain. The framing approach is a suitable
      framework to classify different media representations; it is applied here to
      investigate the frames of scientific evidence in film clips (n=207) taken from
      science television programs. Molecular medicine is the domain of interest for
      this analysis, due to its high proportion of uncertain and conflicting research
      findings and risks. The results indicate that television clips vary in their
      coverage of scientific evidence of molecular medicine. Four frames were found:
      Scientific Uncertainty and Controversy, Scientifically Certain Data, Everyday
      Medical Risks, and Conflicting Scientific Evidence. They differ in their way of
      framing scientific evidence and risks of molecular medicine.

PMID- 24280534
TI  - IMC-PID design based on model matching approach and closed-loop shaping.
AB  - Motivated by the limitations of the conventional internal model control (IMC),
      this communication addresses the design of IMC-based PID in terms of the robust
      performance of the control system. The IMC controller form is obtained by solving
      an H-infinity problem based on the model matching approach, and the parameters
      are determined by closed-loop shaping. The shaping of the closed-loop transfer
      function is considered both for the set-point tracking and for the load
      disturbance rejection. The design procedure is formulated as a multi-objective
      optimization problem which is solved by a specific optimization algorithm. A nice
      feature of this design method is that it permits a clear tradeoff between
      robustness and performance. Simulation examples show that the proposed method is
      effective and has a wide applicability. 

PMID- 24280533
TI  - Genome-wide identification and analysis of Japonica and Indica cultivar-preferred
      transcripts in rice using 983 Affymetrix array data.
AB  - BACKGROUND: Accumulation of genome-wide transcriptome data provides new insight
      on a genomic scale which cannot be gained by analyses of individual data. The
      majority of rice (O. sativa) species are japonica and indica cultivars. Genome
      wide identification of genes differentially expressed between japonica and indica
      cultivars will be very useful in understanding the domestication and evolution of
      rice species. RESULTS: In this study, we analyzed 983 of the 1866 entries in the
      Affymetrix array data in the public database: 595 generated from indica and 388
      from japonica rice cultivars. To discover differentially expressed genes in each
      cultivar, we performed significance analysis of microarrays for normalized data,
      and identified 490 genes preferentially expressed in japonica and 104 genes in
      indica. Gene Ontology analyses revealed that defense response-related genes are
      significantly enriched in both cultivars, indicating that japonica and indica
      might be under strong selection pressure for these traits during domestication.
      In addition, 36 (34.6%) of 104 genes preferentially expressed in indica and 256
      (52.2%) of 490 genes preferentially expressed in japonica were annotated as genes
      of unknown function. Biotic stress overview in the MapMan toolkit revealed key
      elements of the signaling pathway for defense response in japonica or indica
      eQTLs. CONCLUSIONS: The percentage of screened genes preferentially expressed in
      indica was 4-fold higher (34.6%) and that in japonica was 5-fold (52.2%) higher
      than expected (11.1%), suggesting that genes of unknown function are responsible
      for the novel traits that distinguish japonica and indica cultivars. The
      identification of 10 functionally characterized genes expressed preferentially in
      either japonica or indica highlights the significance of our candidate genes
      during the domestication of rice species. Functional analysis of the roles of
      individual components of stress-mediated signaling pathways will shed light on
      potential molecular mechanisms to improve disease resistance in rice.

PMID- 24280535
TI  - Determining rational target for in vivo hedgehog gene therapy.

PMID- 24280536
TI  - Breastfeeding: a potential excretion route for mothers and implications for
      infant exposure to perfluoroalkyl acids.
AB  - BACKGROUND: The presence of perfluoroalkyl acids (PFAAs) in breast milk has been
      documented, but their lactational transfer has been rarely studied. Determination
      of the elimination rates of these chemicals during breastfeeding is important and
      critical for assessing exposure in mothers and infants. OBJECTIVES: We aimed to
      investigate the association between breastfeeding and maternal serum
      concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate
      (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). For
      a subset of the population, for whom we also have their infants' measurements, we
      investigated associations of breastfeeding with infant serum PFAA concentrations.
      METHODS: The present analysis included 633 women from the C8 Science Panel Study
      who had a child < 3.5 years of age and who provided blood samples and reported
      detailed information on breastfeeding at the time of survey. PFAA serum
      concentrations were available for all mothers and 8% (n = 49) of the infants.
      Maternal and infant serum concentrations were regressed on duration of
      breastfeeding. RESULTS: Each month of breastfeeding was associated with lower
      maternal serum concentrations of PFOA (-3%; 95% CI: -5, -2%), PFOS (-3%; 95% CI: 
      3, -2%), PFNA (-2%; 95% CI: -2, -1%), and PFHxS (-1%; 95% CI: -2, 0%). The infant
      PFOA and PFOS serum concentrations were 6% (95% CI: 1, 10%) and 4% (95% CI: 1,
      7%) higher per month of breastfeeding. CONCLUSIONS: Breast milk is the optimal
      food for infants, but is also a PFAA excretion route for lactating mothers and
      exposure route for nursing infants.

PMID- 24280538
TI  - Special issue: In vivo imaging of parasite infection. Preface.

PMID- 24280537
TI  - YGL138(t), encoding a putative signal recognition particle 54 kDa protein, is
      involved in chloroplast development of rice.
AB  - BACKGROUND: Normal development of chloroplast is vitally important to plants, but
      its biological mechanism is still far from fully being understood, especially in
      rice. RESULTS: In this study, a novel yellow-green leaf mutant, ygl138, derived
      from Nipponbare (Oryza sativa L. ssp. japonica) treated by ethyl methanesulfonate
      (EMS), was isolated. The mutant exhibited a distinct yellow-green leaf phenotype
      throughout development, reduced chlorophyll level, and arrested chloroplast
      development. The phenotype of the ygl138 mutant was caused by a single nuclear
      gene, which was tentatively designed as YGL138(t). The YGL138(t) locus was mapped
      to chromosome 11 and isolated into a confined region of 91.8 kb by map-based
      cloning. Sequencing analysis revealed that, Os11g05552, which was predicted to
      encode a signal recognition particle 54 kDa (SRP54) protein and act as a
      chloroplast precursor, had 18 bp nucleotides deletion in the coding region of
      ygl138 and led to a frameshift. Furthermore, the identity of Os11g05552 was
      verified by transgenic complementation. CONCLUSIONS: These results are very
      valuable for further study on YGL138(t) gene and illuminating the mechanism of
      SRP54 protein involving in chloroplast development of rice.

PMID- 24280539
TI  - Inflammatory changes of the nipple areolar complex of a patient with PIP breast
      implants: a possible immune response to free silicone from gel bleed?

PMID- 24280540
TI  - Harvesting free abdominal perforator flaps in the presence of previous upper
      abdominal scars.
AB  - PURPOSE: Subcostal scars pose a risk of upper abdominal flap ischaemia when
      raising a free abdominal flap. The aim of this study was to describe a clinical
      approach to increase flap reliability and donor site healing in the presence of
      transverse abdominal scars while harvesting lower abdominal free flaps. METHODS:
      A total of 11 patients who had subcostal scars and one who had an extended
      subcostal scar (rooftop or chevron incision) underwent free abdominal flaps for
      breast reconstruction. Preoperative radiological imaging was used to evaluate the
      blood supply to the planned flaps. A classification of clinical approaches (I-IV)
      was used. When the cranial (the abdominal closure) flap width was equal to or
      greater than half length, a caudal (the breast) flap could safely be harvested
      (Type I); if not, the cranial flap was enlarged by more caudal flap planning
      (Type II), an oblique design of the free flap (Type III) or by lowering the free
      flap marking more distally (Type IV) with a sparing of the peri-umbilical
      perforators to preserve blood supply to the caudal (abdominal closure) flap.
      RESULTS: Unilateral free deep inferior epigastric perforator (DIEP) and
      superficial inferior epigastric artery (SIEA) flaps were successfully harvested
      in eight and two cases, respectively. In two cases, a bipedicled DIEP/SIEA flap
      was harvested for unilateral breast reconstruction. Slight abdominal wound slough
      occurred in one patient; however, no ischaemia resulted in flaps or at donor
      sites. CONCLUSIONS: Using a pragmatic approach to flap design, based on clinical
      classification, we have found that both flap and donor site morbidity can be
      avoided in patients who have previous upper abdominal scars. LEVEL OF EVIDENCE:
      IV, Therapeutic.

PMID- 24280541
TI  - Removal of a metallic foreign body from the abdominal wall using an orientable
      magnetic locator.

PMID- 24280542
TI  - Layered long-term co-culture of hepatocytes and endothelial cells on a transwell
      membrane: toward engineering the liver sinusoid.
AB  - This paper presents a novel liver model that mimics the liver sinusoid where most
      liver activities occur. A key aspect of our current liver model is a layered co
      culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal
      endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a
      transwell membrane. When a layered co-culture was attempted with a thin Matrigel
      layer placed between hepatocytes and endothelial cells to mimic the space of
      Disse, the cells did not form completely separated monolayers. However, when
      hepatocytes and endothelial cells were cultured on the opposite sides of a
      transwell membrane, PRHs co-cultured with LSECs or BAECs maintained their
      viability and normal morphology for 39 and 57 days, respectively. We assessed the
      presence of hepatocyte-specific differentiation markers to verify that PRHs
      remained differentiated in the long-term co-culture and analyzed hepatocyte
      function by monitoring urea synthesis. We also noted that the expression of
      cytochrome P-450 remained similar in the co-cultured system from day 1 to day 48.
      Thus, our novel liver model system demonstrated that primary hepatocytes can be
      cultured for extended times and retain their hepatocyte-specific functions when
      layered with endothelial cells. 

PMID- 24280545
TI  - [In Process Citation].

PMID- 24280544
TI  - A qualitative assessment of COPD patients' experiences of pulmonary
      rehabilitation and guidance by healthcare professionals.
AB  - BACKGROUND: The present study aimed to assess COPD patients' experiences during
      an in-patient pulmonary rehabilitation program and the guidance provided by
      healthcare professionals. A third aim regarded examining ways to anticipate the
      transfer to the home environment after completion of the program. METHODS: Focus
      groups and semi-structured interviews were used to collect data from seven COPD
      patients at the beginning and six other COPD patients at the end of an in-patient
      pulmonary rehabilitation program, supplemented by a focus group and semi
      structured interviews with 14 healthcare professionals of the involved
      disciplines. Data were analyzed using a phenomenological approach. RESULTS:
      Starting out, patients displayed trouble with acceptance of their disease, they
      had insufficient knowledge, and showed difficulties in setting specific realistic
      goals. Seeing fellow patients struggle with similar problems and tailored
      counseling by healthcare professionals helped them to overcome these barriers.
      During rehabilitation, patients became more confident in exercising and managing
      their daily life activities. Many patients evolved a desire to self-regulate
      their lives. Incorporating health-enhancing behaviors after returning home into
      their usual daily routines was anticipated to be tough. CONCLUSION: Patients
      undergoing pulmonary rehabilitation experience a complex health behavior change
      process, in which healthcare professionals fulfill a major contributing role.
      Therefore, guiding patients through this health behavior change process is a
      vital component of healthcare professionals' work, regarding which the present
      study made practical implications such as applying a personalized approach by
      giving tailored advices, applying an autonomy-supportive counseling style,
      teaching self-management skills, and referring patients to local exercise
      facilities.

PMID- 24280543
TI  - The clinical impact of non-obstructive chronic bronchitis in current and former
      smokers.
AB  - BACKGROUND: As the clinical significance of chronic bronchitis among smokers
      without airflow obstruction is unclear, we sought to determine morbidity
      associated with this disorder. METHODS: We examined subjects from the COPDGene
      study and compared those with FEV1/FVC >= 0.70, no diagnosis of asthma and
      chronic bronchitis as defined as a history of cough and phlegm production for >=
      3 months/year for >= 2 years (NCB) to non-obstructed subjects without chronic
      bronchitis (CB-). Multivariate analysis was used to determine factors associated
      with and impact of NCB. RESULTS: We identified 597 NCB and 4283 CB- subjects. NCB
      participants were younger (55.4 vs. 57.2 years, p < 0.001) with greater tobacco
      exposure (42.9 vs. 37.8 pack-years, p < 0.001) and more often current smokers;
      more frequently reported occupational exposure to fumes (52.8% vs. 42.2%, p <
      0.001), dust for >= 1 year (55.3% vs. 42.0%, p < 0.001) and were less likely to
      be currently working. NCB subjects demonstrated worse quality-of-life (SGRQ 35.6
      vs. 15.1, p < 0.001) and exercise capacity (walk distance 415 vs. 449 m, p <
      0.001) and more frequently reported respiratory "flare-ups" requiring treatment
      with antibiotics or steroids (0.30 vs. 0.10 annual events/subject, p < 0.001)
      prior to enrollment and during follow-up (0.34 vs. 0.16 annual events/subject, p
      < 0.001). In multivariate analysis, current smoking, GERD, sleep apnea and
      occupational exposures were significantly associated with NCB. CONCLUSIONS: While
      longitudinal data will be needed to determine whether NCB progresses to COPD, NCB
      patients have poorer quality-of-life, exercise capacity and frequent respiratory
      events. Beyond smoking cessation interventions, further research is warranted to
      determine the benefit of other therapeutics in this population. Clinical Trials
      Registration # NCT00608764 (http://clinicaltrials.gov/show/NCT00608764). Link to
      study protocol: http://www.copdgene.org/sites/default/files/COPDGeneProtocol-5
      0_06-19-2009.pdf.

PMID- 24280546
TI  - [Skeletal Class II treatment with the miniscrew-anchored Herbst].
AB  - No-compliance orthodontic treatment has recently become very popular. Unlike
      removable appliances requiring patient compliance, the Herbst appliance is a
      widely used fixed functional bite-jumping device generating predictable results
      in the treatment of skeletal class II malocclusions. The main problem associated
      with tooth-borne bite-jumping appliances is the generation of unavoidable dental
      movements, especially proclination of lower incisors, in addition to the skeletal
      effect. These dento-alveolar compensations can, when uncontrolled, compromise
      treatment results. This article describes two cases managed with a new treatment
      protocol based on the association of a modified Herbst appliance and temporary
      skeletal anchorage devices (TSADs) for efficient treatment of skeletal class II
      malocclusions. 

PMID- 24280547
TI  - [Translation and cultural adaptation of a french version of the psychosocial
      impact of dental aesthetics questionnaire: PIDAQ].
AB  - The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) is a tool
      developed and validated to specifically assess subject's quality of life related
      to orthodontic anomalies. The aims of the present study were to translate and
      culturally adapt the PIDAQ's native English version into French, and to test the
      psychometric characteristics of the version thereby obtained. Toward these ends,
      the PIDAQ's original English version was translated into French and back
      translated into English following the prescribed guidelines. Each of the versions
      obtained from the translation process was further subjected to a committee
      review. The final French version which is named QIPEO underwent an analysis of
      psychometric properties on a sample of 42 subjects (33 females and 9 males, aged
      24.60 +/- 8.66 years). Internal consistency was good with Cronbach ff
      coefficients ranging from 0.67 for "aesthetic concerns" to 0.87 for "social
      impact". The reproducibility of the responses given by 14 subjects after 15 days
      interval was correct with intraclass coefficients ranging from 0.72 for "social
      impact" to 0.90 for "aesthetic concerns". Furthermore, the different subscales of
      the French version of the PIDAQ showed excellent correlation with the perception
      of aesthetics and fairly good correlation with self-perception of orthodontic
      treatment need. Definite need for orthodontic treatment, as assessed normatively
      by the IOTN, was significantly associated with lower scores of "self-confidence"
      and higher scores of "social impact", "psychological impact" and "aesthetic
      concerns". Overall, the French version of the PIDAQ was shown to be reliable and
      has some validity for use in this population. Further studies including a larger
      sample size is recommended to reassess the validation and the responsiveness of
      this French version. 

PMID- 24280548
TI  - [Treatment of ankylosed teeth by segmental corticotomy: the Orthodontic Bone
      Stretching technique. Preliminary study].
AB  - Ankylosed anterior teeth are associated with infraclusion and can lead to a
      concomitant significant esthetic defect. After a review of the techniques used
      move these teeth into the arch, this article describes a new technique to restore
      occlusion and improve esthetics, or to prepare the case for either a prosthetic
      or implant treatment, Orthodontic Bone Stretching (OBS). This technic combines
      partial corticotomy and orthodontic treatment and produces bone stretching. After
      8 to 12 weeks of force application, the ankylosed teeth are repositioned into
      occlusion or, if extraction is necessary, the bone crest is at a level consistent
      with a prosthetic or implant treatment. OBS technique can be adapted to implant
      infraclusion, or the vertical regeneration of atrophied ridge. 

PMID- 24280549
TI  - [New developments in cephalometrics].
AB  - Recently l recalled the error in the principle which makes cephalometric analysis
      unsuitable for orthodontic diagnosis. Now, three methods of analysis have been
      published precisely conceived in order to avoid this error. Will cephalometric
      analysis succeed in its search for the truth? 

PMID- 24280550
TI  - [Combined use of Beneslider and lingual braces, mechanical aspects and
      procedures].
AB  - Over the last years, a tendency to prefer purely intra-oral appliances with
      minimal need for patient cooperation is noticed if upper molars should be
      distalized. Unfortunately, most of the conventional devices for non-compliance
      upper molar distalization produce unwanted side effects such as anchorage loss.
      To minimize or eliminate anchorage loss, mini-screws attracted a great attention
      in recent years because of minimal surgical invasiveness and low cost. Using the
      anterior palate as an insertion site, the failure rate is extremely low, there is
      no risk of root damage and the appliances are out of the path of tooth movement.
      Based on comprehensive clinical documentation, the rational and practical
      applications of the Beneslider in combination with lingual braces are presented.
      By this procedure, extractions in the upper arch and reactive forces in the lower
      arch resulting in a protrusion of the incisors can be avoided with an invisible
      treatment appliance. 

PMID- 24280551
TI  - [Orthodontics and cosmetic composite for treatment ending: ultra conservative
      approach of the smile restoring].
AB  - Thanks to alignment, bleaching and bonding, cosmetic dentistry is rising. The
      cases presented in this article are treated through minimal invasive dentistry
      linked to orthodontics. 

PMID- 24280552
TI  - [Evaluation of the corrosion resistance of orthodontic wires by electrochemical
      measures and scanning electron microscopy (SEM)].
AB  - The objective of this paper is to study the corrosion resistance of orthodontic
      wires made of different alloys (stainless steel, chrome-cobalt, nickel-titanium
      and beta-titanium) and for the same alloy from different vendors (GAC((r)),
      RMO((r)), 3M((r)) and ORMCO((r))). Different electrochemical techniques
      (corrosion potential monitoring as a function of immersion time, current
      potential curves, electrochemical impedance spectroscopy (EIS)) were used. The
      wires' resistance to corrosion was measured and compared with the surface
      condition, assessed by scanning electron microscopy (SEM). Using the recorded
      data, a rating system based on the corrosion resistance of orthodontic wires was
      developed. The comparison of these data with the results of SEM shows that the
      surface chemical composition plays a primary role in the electrochemical behavior
      of the orthodontic wires and, unlike surface defects, is a key parameter for the
      corrosion resistance of the alloy. 

PMID- 24280553
TI  - [In Process Citation].

PMID- 24280554
TI  - Can corrective information reduce negative appraisals of intrusive thoughts in a
      community sample?
AB  - BACKGROUND: Improving mental health literacy in the general population is
      important as it is associated with early detection and treatment-seeking for
      mental health problems. Target areas for mental health literacy programs should
      be guided by research that tests the impact of improving knowledge of
      psychological constructs associated with the development of mental health
      problems. AIMS: This study investigated the impact of providing corrective
      information about the nature of intrusive thoughts on their subsequent appraisal
      in a community sample. METHOD: In an online, experimental design, 148 community
      participants completed measures of obsessive-compulsive symptoms and appraisals
      (Obsessive Compulsive Inventory-Revised [OCI-R]; Intrusions Inventory [III]).
      Individuals were instructed to read either a brief informational text about the
      nature of intrusive thoughts or a control text. All participants then completed
      post-test measurements of appraisals. Intervention effectiveness was analysed
      using hierarchical multiple regression. RESULTS: Individuals in the intervention
      group reported significantly lower levels of maladaptive appraisals than those in
      the control group (alpha = .05). CONCLUSIONS: The results of this study support
      the efficacy of provision of brief written information in reducing negative
      appraisals of intrusive thoughts in a community sample. It suggests a possible
      role for education about intrusive thoughts as a prevention strategy for
      obsessive-compulsive disorder.

PMID- 24280555
TI  - Relationship between 22-kHz calls and testosterone in male rats.
AB  - Ultrasonic calls in rats induced by the presence of a predator, referred to as
      "22-kHz calls," are mainly emitted by socially dominant male rats. Testosterone
      levels are closely related to social dominance in male rats. In the present
      study, we investigated the relationship between the emission of stress-induced 22
      kHz calls and circulating testosterone levels in male rats, using a combination
      of surgery (castration or sham operation) and chronic steroid administration
      (testosterone or cholesterol) to modify circulating testosterone levels. We also
      assessed the effects of androgen and/or estrogen receptor antagonists on the
      emission of 22-kHz calls in male rats. An air puff stimulus, known to reliably
      induce 22-kHz calls in rats, was used as a stressor. Castrated rats with
      cholesterol implants exhibited significantly fewer 22-kHz calls than rats that
      had received a sham operation and cholesterol implants, and there was no
      significant difference between castrated rats with testosterone implants and rats
      that had received a sham operation and cholesterol implants. Only male rats
      pretreated with a binary mixture of androgen and estrogen antagonists exhibited
      significantly fewer 22-kHz calls than controls. These results show that
      testosterone in male rats has a positive effect on the emission of stress-induced
      22-kHz calls, and the calls may be regulated by the activation of both androgen
      and estrogen receptors. 

PMID- 24280556
TI  - Classification of body movements based on posturographic data.
AB  - The human body, standing on two feet, produces a continuous sway pattern.
      Intended movements, sensory cues, emotional states, and illnesses can all lead to
      subtle changes in sway appearing as alterations in ground reaction forces and the
      body's center of pressure (COP). The purpose of this study is to demonstrate that
      carefully selected COP parameters and classification methods can differentiate
      among specific body movements while standing, providing new prospects in camera
      free motion identification. Force platform data were collected from participants
      performing 11 choreographed postural and gestural movements. Twenty-three
      different displacement- and frequency-based features were extracted from COP time
      series, and supplied to classification-guided feature extraction modules. For
      identification of movement type, several linear and nonlinear classifiers were
      explored; including linear discriminants, nearest neighbor classifiers, and
      support vector machines. The average classification rates on previously unseen
      test sets ranged from 67% to 100%. Within the context of this experiment, no
      single method was able to uniformly outperform the others for all movement types,
      and therefore a set of movement-specific features and classifiers is recommended.

PMID- 24280557
TI  - Body size and countermovement depth confound relationship between muscle power
      output and jumping performance.
AB  - A number of studies based on maximum vertical jumps have presumed that the
      maximum jump height reveals the maximum power of lower limb muscles, as well as
      the tested muscle power output predicts the jumping performance. The objective of
      the study was to test the hypothesis that both the body size and countermovement
      depth confound the relationship between the muscle power output and performance
      of maximum vertical jumps. Sixty young and physically active males were tested on
      the maximum countermovement (CMJ) and squat jumps (SJ). The jumping performance
      (Hmax), peak (Ppeak) and the average power output (Pavg) during the concentric
      phase, countermovement depth (only in CMJ) and body mass as an index of body size
      were assessed. To assess the power-performance relationship, the correlations
      between Hmax with both Ppeak and Pavg were calculated without and with
      controlling for the effects of body mass, as well as for the countermovement
      depth. The results revealed moderate power-performance relationships (range
      .55<r<.64) that were comparable for CMJ and SJ jumps. When controlled for body
      mass, the same values were markedly higher (.61<r<.82; p<.05 for Ppeak of both
      jumps). When controlled for both the body mass and countermovement depth, CMJ
      revealed r=.88 and r=.77 for Ppeak and Pavg, respectively. Both jumps revealed
      stronger relationships with Ppeak than with Pavg (p<.05) when controlled for
      either body mass or both body mass and countermovement depth. We conclude that
      both body size (in CMJ and SJ) and countermovement depth (in CMJ) confound the
      relationship between the muscle power output with the performance of maximum
      vertical jumps. Regarding routine assessments of muscle power from jumping
      performance and vice versa, the use of CMJ is recommended, while Ppeak, rather
      than Pavg, should be the variable of choice. 

PMID- 24280558
TI  - Dispersal pattern and dispersion of adult and nymph stink bugs (Hemiptera:
      Pentatomidae) in wheat and corn.
AB  - Euschistus servus (Say) can develop a generation on wheat, Triticum aestivum L.,
      before moving to corn, Zea mays L., where it can be a pest. Because effective
      management methods are unknown, this study sought to describe the spatial
      distribution and dispersal of E. servus in the wheat and corn interface. In
      addition, Oebalus pugnax (F.) densities were documented in both crops. Wheat
      fields adjacent to the corn were sampled before harvest and stink bugs were
      marked using a product containing egg whites. Dispersal into the adjacent corn
      was measured using grid sampling, and dispersion was measured over time using an
      immunoassay targeting egg albumin on E. servus collected in corn. Dispersion was
      measured using Anselin Local Moran's I for unmarked stink bugs only. O. pugnax
      was prominent in wheat but was rarely recovered from corn. In contrast, E. servus
      was common in wheat during both years and dispersed into the adjacent corn. E.
      servus nymph and adult densities increased quadratically over time in corn in
      2011. In contrast, E. servus nymph densities decreased over time in corn in 2012,
      while adult densities remained static. Most aggregations of E. servus nymphs and
      adults were located on the edge of the corn, directly adjacent to the harvested
      wheat. This is likely the first study to directly document the movement of E.
      servus nymphs to the adjacent crop. Movement from wheat to corn was not
      consistent between the years and may have been influenced by factors such as
      variations in weather, timing of wheat harvest, or other available alternative
      hosts. 

PMID- 24280559
TI  - Diabetic foot cellular hypoxia may be due to capillary shunting--a novel
      hypothesis.
AB  - Diabetic foot is traditionally attributed to a triad of neuropathy, ischemia and
      infection. Cellular hypoxia in diabetic foot can neither be attributed to an
      occlusive large artery disease (which are mostly patent) nor to the so called
      diabetic small vessel disease (where such occlusion was never proved). The
      physiological findings that accompany cellular hypoxia are confusing: elevated
      local blood flow and high oxygen saturation in both the tissue and its collecting
      veins. It is well known that some tissues (e.g. skin) are wired with two types of
      capillaries: True capillaries - also known as exchange capillaries, where
      nutrients and gases exchange takes place, and metarteriole thoroughfare channels 
      also known as shunting capillaries. We hypothesize that in the diabetic foot
      tissue blood flow is rerouted through the metarteriole thoroughfare channel,
      bypassing the exchange capillaries. Hence, nutrient and gas exchange is disabled
      and tissue cells became hypoxic regardless of the tissue blood flow. As a result
      of the shunt, arterial oxygen is not consumed and the oxygen saturation in the
      collecting veins remains high. The hereby hypothesis suggests that mal-perfusion
      rather than hypo-perfusion is the underlying cause of cellular hypoxia in
      diabetic foot. This hypothesis complies with the findings of patent arteries
      proximal to the affected site, normal to elevated tissue blood flow and high
      oxygen saturation in the affected tissue and its collecting veins. 

PMID- 24280560
TI  - Non-alcoholic fatty liver disease; a part of the metabolic syndrome in the renal
      transplant recipient and possible cause of an allograft dysfunction.
AB  - Despite all improvements in transplant medicine, renal transplant recipients have
      a high risk for cardiovascular mortality. A high prevalence of cardiovascular
      complications in renal transplant recipients (RTR) is explained by cardiovascular
      risk factors present before transplantation, in addition to the development of
      new risk factors as well as worsening of preexisting risk factors after
      transplantation. A majority ot these patients develop metabolic syndrome within a
      year after the transplantation. The metabolic syndrome (MS) is associated with
      impaired renal allograft function and increased insulin resistance. Non alcoholic
      fatty liver disease (NAFLD) represents a liver manifestation of metabolic
      syndrome and it development is strongly associated with all components of MS in
      general population. The current importance of NAFLD and its link to the MS has
      encouraged an interest in its possible role in the development of atherosclerosis
      in recent years. Considering the fact that all components of MS are more common
      among renal transplant recipients compared to general population, it would be
      expected that RTR may have a much higher incidence of NAFLD compared to general
      population. We propose that the presence of NAFLD in RTR could be a strong
      predictor in cardiovascular morbidity and mortality. Also, according to the
      recent investigations about the possible link between NAFLD and chronic kidney
      disease, we hypothesis that NAFLD may be associated with deteriorating graft
      function, causing a chronic allograft nephropathy and graft loss. Common factors
      underlying the pathogenesis of NAFLD and chronic allograft dysfunction may be
      insulin resistance, oxidative stress, activation of rennin-angiotensin system,
      and inappropriate secretion of inflammatory cytokines by steatotic and inflamed
      liver. 

PMID- 24280561
TI  - Music intervention as system: reversing hyper systemising in autism spectrum
      disorders to the comprehension of music as intervention.
AB  - This paper seeks to combine the notion of the Empathising-Systemising (E-S)
      theory and the resulting twist from the executive dysfunction theory in autism
      spectrum conditions (ASC) in light of music intervention as system. To achieve
      these points it will be important to re-visit, nonetheless briefly, the above
      mentioned theories and re-define music intervention in the light of these.
      Furthermore there is the need to adjust the executive dysfunction theory to a
      theory of dysfunctioning executive functions. These notions will create a
      different understanding of music intervention in this context, allowing the
      development of future and existing music intervention programs applied
      clinically. These applications will evolve around a structuralised approach to
      music intervention as system, proposing five consecutive systems. It will
      therefore argue the aspects of expanding existing theories in ASC together with
      the call for generalised interventions to better assess autism from a theoretical
      point of view. Theories have to be updated in a time of fast and ever-changing
      development. 

PMID- 24280562
TI  - 5-HTP hypothesis of schizophrenia.
AB  - INTRODUCTION AND AIMS: To pose a new hypothesis of schizophrenia that affirms and
      unifies conventional hypotheses. METHODS: Outside the brain, there are 5-HTP
      containing argyrophil cells that have tryptophan hydroxylase 1 without l-aromatic
      amino acid decarboxylase. Monoamine oxidase in the liver and lung metabolize 5
      HT, rather than 5-HTP, and 5-HTP freely crosses the blood-brain barrier,
      converting to 5-HT in the brain. Therefore I postulate that hyperfunction of 5
      HTP-containing argyrophil cells may be a cause of schizophrenia. I investigate
      the consistency of this hypothesis with other hypotheses using a deductive
      method. RESULTS: Overactive 5-HTP-containing argyrophil cells produce excess
      amounts of 5-HTP. Abundant 5-HTP increases 5-HT within the brain (linking to the
      5-HT hypothesis), and leads to negative feedback of 5-HT synthesis at the rate
      limiting step catalysed by tryptophan hydroxylase 2. Owing to this negative
      feedback, brain tryptophan is further metabolized via the kynurenine pathway.
      Increased kynurenic acid contributes to deficiencies of glutamate function and
      dopamine activity, known causes of schizophrenia. CONCLUSIONS: The 5-HTP
      hypothesis affirms conventional hypotheses, as the metabolic condition caused by
      acceleration of tryptophan hydroxylase 1 and suppression of tryptophan
      hydroxylase 2, activates both 5-HT and kynurenic acid. In order to empirically
      test the theory, it will be useful to monitor serum 5-HTP and match it to
      different phases of schizophrenia. This hypothesis may signal a new era with
      schizophrenia treated as a brain-gut interaction.

PMID- 24280563
TI  - Design and validation of a computer-aided learning program to enhance students'
      ability to recognize lameness in the horse.
AB  - The ability to recognize lameness in the horse is an important skill for
      veterinary graduates; however, opportunities to develop this skill at the
      undergraduate level are limited. Computer-aided learning programs (CALs) have
      been successful in supplementing practical skills teaching. The aim of this study
      was to design and validate a CAL for the teaching of equine lameness recognition
      (CAL1). A control CAL was designed to simulate learning by experience (CAL2).
      Student volunteers were randomly assigned to either CAL and tested to establish
      their current ability to recognize lameness. Retesting occurred both immediately
      following exposure and 1 week later. At each test point, the number of correct
      responses for forelimb and hind limb cases was determined. Student confidence was
      assessed before and after CAL exposure, with previous opportunities to recognize
      lameness taken into account. Immediately following exposure, the number of
      correct responses was significantly higher for CAL1 than for CAL2, both overall
      and for forelimb cases but not for hind limb cases. After 1 week, the CAL1 group
      performed significantly better overall compared to the CAL2 group, with no
      significant difference between forelimb and hind limb cases. Student confidence
      and ability to recognize lameness were significantly improved following exposure
      to CAL1. When considered as one category, students in years 4 and 5 performed
      significantly better than year 3 students. Gender did not significantly affect
      performance. CAL1 could be used to supplement current lameness recognition
      opportunities. CAL1 is, however, limited in its ability to improve lameness
      recognition, especially in relation to hind limb lameness where it was unable to
      attain a significant difference from CAL2.

PMID- 24280564
TI  - Biomechanical and structural response of healing Achilles tendon to fatigue
      loading following acute injury.
AB  - Achilles tendon injuries affect both athletes and the general population, and
      their incidence is rising. In particular, the Achilles tendon is subject to
      dynamic loading at or near failure loads during activity, and fatigue induced
      damage is likely a contributing factor to ultimate tendon failure. Unfortunately,
      little is known about how injured Achilles tendons respond mechanically and
      structurally to fatigue loading during healing. Knowledge of these properties
      remains critical to best evaluate tendon damage induction and the ability of the
      tendon to maintain mechanical properties with repeated loading. Thus, this study
      investigated the mechanical and structural changes in healing mouse Achilles
      tendons during fatigue loading. Twenty four mice received bilateral full
      thickness, partial width excisional injuries to their Achilles tendons (IACUC
      approved) and twelve tendons from six uninjured mice were used as controls.
      Tendons were fatigue loaded to assess mechanical and structural properties
      simultaneously after 0, 1, 3, and 6 weeks of healing using an integrated
      polarized light system. Results showed that the number of cycles to failure
      decreased dramatically (37-fold, p<0.005) due to injury, but increased throughout
      healing, ultimately recovering after 6 weeks. The tangent stiffness, hysteresis,
      and dynamic modulus did not improve with healing (p<0.005). Linear regression
      analysis was used to determine relationships between mechanical and structural
      properties. Of tendon structural properties, the apparent birefringence was able
      to best predict dynamic modulus (R(2)=0.88-0.92) throughout healing and fatigue
      life. This study reinforces the concept that fatigue loading is a sensitive
      metric to assess tendon healing and demonstrates potential structural metrics to
      predict mechanical properties. 

PMID- 24280565
TI  - Functional analysis of limb recovery following autograft treatment of volumetric
      muscle loss in the quadriceps femoris.
AB  - Severe injuries to the extremities often result in muscle trauma and, in some
      cases, significant volumetric muscle loss (VML). These injuries continue to be
      challenging to treat, with few available clinical options, a high rate of
      complications, and often persistent loss of limb function. To facilitate the
      testing of regenerative strategies for skeletal muscle, we developed a novel
      quadriceps VML model in the rat, specifically addressing functional recovery of
      the limb. Our outcome measures included muscle contractility measurements to
      assess muscle function and gait analysis for evaluation of overall limb function.
      We also investigated treatment with muscle autografts, whole or minced, to
      promote regeneration of the defect area. Our defect model resulted in a loss of
      muscle function, with injured legs generating less than 55% of muscle strength
      from the contralateral uninjured control legs, even at 4 weeks post-injury. The
      autograft treatments did not result in significant recovery of muscle function.
      Measures of static and dynamic gait were significantly decreased in the
      untreated, empty defect group, indicating a decrease in limb function.
      Histological sections of the affected muscles showed extensive fibrosis,
      suggesting that this scarring of the muscle may be in part the cause of the loss
      of muscle function in this VML model. Taken together, these data are consistent
      with clinical findings of reduced muscle function in large VML injuries. This new
      model with quantitative functional outcome measures offers a platform on which to
      evaluate treatment strategies designed to regenerate muscle tissue volume and
      restore limb function. 

PMID- 24280566
TI  - Polyfluoroalkyl chemicals and menopause among women 20-65 years of age (NHANES).
AB  - BACKGROUND: Polyfluoroalkyl chemicals (PFCs) such as perfluorooctane sulfonate
      (PFOS) and perfluorooctanoate (PFOA) have been associated with early menopause.
      However, previous cross-sectional studies have lacked adequate data to
      investigate possible reverse causality (i.e., higher serum concentrations due to
      decreased excretion after menopause). OBJECTIVES: We investigated the association
      between PFOS, PFOA, perfluorononanoate (PFNA), and perfluorohexane sulfonate
      (PFHxS) and age at natural menopause among women 20-65 years of age in NHANES
      (National Health and Nutrition Examination Survey). METHODS: We used proportional
      hazard models to estimate hazard ratios (HRs) for the onset of natural menopause
      as a function of age and serum PFC levels, and to investigate reverse causation
      by estimating associations between PFC levels and the rate of hysterectomy. We
      also used multivariable linear regression to determine whether time since
      menopause predicted serum PFC levels. RESULTS: After adjusting for age at survey,
      race/ethnicity, education, ever smoking, and parity, women with higher levels of
      PFCs had earlier menopause than did women with the lowest PFC levels. We observed
      a monotonic association with PFHxS: The HR was 1.42 (95% CI: 1.08, 1.87) for
      serum concentrations in tertile 2 versus tertile 1, and 1.70 (95% CI: 1.36, 2.12)
      for tertile 3 versus tertile 1. We also found evidence of reverse causation: PFCs
      were positively associated with rate of hysterectomy, and time since natural
      menopause was positively associated with serum PFCs. CONCLUSIONS: Our findings
      suggest a positive association between PFCs and menopause; however, at least part
      of the association may be due to reverse causation. Regardless of underlying
      cause, women appear to have higher PFC concentrations after menopause.

PMID- 24280567
TI  - Seroprevalence of Toxoplasma gondii in wild boars (Sus scrofa) from Central
      Italy.
AB  - Wild and farmed game meat consumption has been highlighted as an emerging risk
      factor for Toxoplasma gondii infection in humans. In Central Italy wild boar is
      widely distributed and is also one of the most popular game species. The main
      goal of the present study was to estimate the seroprevalence of T. gondii
      antibodies through a serological survey conducted on 400 hunted wild boars (250
      males and 150 females) during three subsequent hunting seasons (2009-2011), using
      an Immunofluorescence Antibody Assay. The animals were sorted by age, determined
      on the evaluation of the dental table; 101 were <1 year old, 175 from 1 to 3
      years, and 124 > 3 years. Antibodies against T. gondii were detected in 56 (14%)
      serum samples with titers ranging from 40 to >=160; a significant association (p
      < 0.05) was found between seropositivity and age, but not gender, hunting
      districts, or year of sampling.

PMID- 24280568
TI  - From the editor.

PMID- 24280569
TI  - Human equilibrative nucleoside transporter 1 (hENT1): do we really have a new
      predictive biomarker of chemotherapy outcome in pancreatic cancer patients?
AB  - Although systemic chemotherapy significantly improves the overall survival of
      pancreatic cancer patients, the prognosis remains extremely poor. The development
      of a drug resistance, either de novo or induced resistance, significantly limits
      the effectiveness of chemotherapy. SLC29A1 gene encodes human equilibrative
      nucleoside transporter 1 (hENT1) protein that is mediating the transport of
      nucleotides, both purines and pyrimidines, into the tumor cells. The aim of this
      mini-review is to summarize the current information concerning the prognostic and
      predictive role of SLC29A1 transporter (hENT1) expression in pancreatic cancer.
      Increased expression of SLC29A1 in vitro has been described as a potential
      critical factor determining the sensitivity of pancreatic cancer cells to
      gemcitabine and 5-fluorouracil, the principal cytotoxic agents used in the
      treatment of pancreatic cancer. The reports on the relationship between SLC29A1
      expression and prognosis of patients with pancreatic cancer are currently rather
      conflicting. However, majority of studies on patients with resected pancreatic
      cancer have suggested that high SLC29A1expression may be predictive of improved
      survival in patients treated with gemcitabine. SLC29A1 has not been shown to
      represent a predictive biomarker for patients treated by 5-fluorouracil. In
      conclusion, potential prognostic and predictive role of SLC29A1 has been
      demonstrated for selected subset of patients. 

PMID- 24280570
TI  - B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic
      cancer.
AB  - OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal tumors of the
      gastrointestinal tract. The ability to predict which patients would benefit most
      from surgical intervention and chemotherapy would be a great clinical tool. A
      large number of potential markers have been identified lately in pancreatic
      cancer and their clinical utilities as prognostic tools are under investigation.
      METHODS: We recruited 41 patients who had undergone radical surgical resection
      for PC between 2003 and 2010. To investigate the prognostic factors, we evaluated
      3 possible markers: B7H4, HSP27 and DJ-1 protein expressions in the tissue
      specimens of these 41 patients by immunohistochemistry and analyzed the clinical
      and pathological features of these specimens. RESULTS: The expression of the
      three antigens was independently associated with a negative impact of
      chemotherapy with gemcitabine on patient's survival. Moreover, patients who
      overexpressed B7H4 had worse prognosis than the ones who did not. CONCLUSIONS:
      B7H4, DJ-1 and HSP27 may be used in the future as prognostic markers that express
      resistance of pancreatic cancer patients to chemotherapy with gemcitabine.

PMID- 24280571
TI  - Computed tomography staging of pancreatic cancer: a validation study addressing
      interobserver agreement.
AB  - BACKGROUND/OBJECTIVES: Ductal adenocarcinoma in the head of the pancreas (PDAC)
      is usually unresectable at the time of diagnosis due to the involvement of the
      peripancreatic vessels. Various preoperative classification algorithms have been
      developed to describe the relationship of the tumor to these vessels, but most of
      them lack a surgically based approach. We present a CT-based classification
      algorithm for PDAC based on surgical resectability principles with a focus on
      interobserver variability. METHODS: Thirty patients with PDAC undergoing
      pancreaticoduodenectomy were examined by using a standard CT protocol. Nine
      radiologists, representing three different levels of expertise, evaluated the CT
      examinations and the tumors were classified into four categories (A-D) according
      to the proposed system. For the interobserver agreement, the Intraclass
      Correlation Coefficient (ICC) was estimated. RESULTS: The overall ICC was 0.94
      and the ICCs among the trainees, experienced radiologists, and experts were 0.85,
      0.76, and 0.92, respectively. All tumors classified as category A1 showed no
      signs of vascular invasion at surgery. In category A2, 40% of the tumors had
      corresponding infiltration and required resection of the superior mesenteric
      vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in
      category C required SMV/PV resection. All six patients in category D had both
      arterial and venous involvement. CONCLUSION: There is almost perfect agreement
      among radiologists with different levels of expertise in regards to the local
      staging of PDAC. For tumors in a more advanced preoperative category, an
      increased risk for vascular involvement was noticed at surgery.

PMID- 24280572
TI  - Chemoradiation for resected pancreatic adenocarcinoma with or without
      intraoperative radiation therapy boost: Long-term outcomes.
AB  - BACKGROUND/OBJECTIVES: To analyze prognostic factors associated with long-term
      outcomes in patients with pancreatic cancer treated with chemoradiation therapy
      (CRT) and surgery with or without intraoperative electron beam radiotherapy
      (IOERT). PATIENTS AND METHODS: From January 1995 to December 2012, 60 patients
      with adenocarcinoma of the pancreas and locoregional disease (clinical stage IB
      [n = 13; 22%], IIA [n = 16; 27%], IIB [n = 22; 36%], IIIC [n = 9; 15%]) were
      treated with CRT (45-50.4 Gy before surgery [n = 19; 32%] and after surgery [n =
      41; 68%]) and curative resection (R0 [n = 34; 57%], R1 [n = 26, 43%]). Twenty
      nine patients (48%) also received a pre-anastomosis IOERT boost (applicator
      diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV). RESULTS: With a
      median follow-up of 15.9 months (range, 1-182), 5-year overall survival (OS),
      disease-free survival (DFS), and locoregional control were 20%, 13%, and 58%,
      respectively. Univariate analyses showed that R1 margin resection status (HR,
      3.17; p = 0.04), not receiving IOERT (HR, 7.33; p = 0.01), and postoperative CRT
      (HR, 5.12; p = 0.04) were associated with a higher risk of locoregional
      recurrence. In the multivariate analysis, only margin resection status (HR, 3.0;
      p = 0.05) and not receiving IOERT (HR, 6.75; p = 0.01) retained significance with
      regard to locoregional recurrence. Postoperative mortality and perioperative
      complications were 3% (n = 2) and 43% (n = 26). CONCLUSIONS: Although local
      control is good in the radiation-boosted area, OS remains modest owing to high
      risk of distant metastases. Intensified locoregional treatment needs to be tested
      in the context of more efficient systemic therapy.

PMID- 24280573
TI  - MUC2 expression and prevalence of high-grade dysplasia and invasive carcinoma in
      mixed-type intraductal papillary mucinous neoplasm of the pancreas.
AB  - BACKGROUND/OBJECTIVES: Morphological types and mucin protein expressions classify
      intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly
      consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN
      mostly consists of gastric type (G-type), which does not express MUC2. However,
      the definition of mixed-type IPMN has yet to be clarified and it contains various
      histological types. The aim of this study was to investigate the relationship
      between MUC2 expression and the presence of high-grade dysplasia (HGD) and
      invasive carcinoma, especially in mixed-type IPMN. METHODS: This retrospective
      study included 101 consecutive patients with surgically resected IPMNs between
      April 2001 and October 2012. All patients were morphologically classified into
      four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type:
      oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies
      were investigated. RESULTS: According to the classification of the 2012
      international guidelines, the numbers (and histomorphological types: I/G/PB/O) of
      MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40
      (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were
      75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of
      HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than
      that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017;
      invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that
      MUC2 expression is an independent predictive factor of HGD and invasive carcinoma
      in mixed IPMN (odds ratio 14.6, 95% CI 2.5-87.4, p = 0.003). CONCLUSIONS: In
      mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma
      and may provide most appropriate surgical indication.

PMID- 24280574
TI  - The role of lymph node ratio in recurrence after curative surgery for pancreatic
      endocrine tumours.
AB  - BACKGROUND: The prognostic role of lymph nodes metastasis in pancreatic
      neuroendocrine tumours is unclear. METHODS: Retrospective study of 53 patients
      who underwent a curative standard resection for pancreatic neuroendocrine
      tumours. The endpoint was to define the role of the lymph nodes ratio in
      recurrence after curative surgery. The following data were considered as possible
      factors for predicting the risk of recurrence: gender, age, presence of symptoms,
      hormonal status, site of tumours, type of resection, size of the tumours, radical
      resection, pathological T, N and M stage, the Ki67 index, the number of lymph
      nodes harvested, the number of metastatic lymph nodes and the lymph node ratio.
      Recurrence rate and time of recurrence were evaluated. RESULTS: Twelve (26.4%)
      patients developed a recurrence with a median time of 42.8 (1-305) months. At
      multivariate analysis, the only factors related to recurrence were: size of
      lesions (HR 1.1, C.I. 95% 1.0-1.1, P = 0.011), Ki67 >= 5% (HR 3.6, C.I. 95% 1.3
      10, P = 0.014) and LNR > 0.07 (HR 5.2, C.I. 95% 1.1-25, P = 0.045). CONCLUSIONS:
      Our study confirmed that the lymph nodes ratio played an important role in the
      recurrence rate and suggested that a low number of metastatic lymph nodes reduced
      the disease free survival.

PMID- 24280575
TI  - Electroacupuncture treatment for pancreatic cancer pain: a randomized controlled
      trial.
AB  - BACKGROUND: Pancreatic cancer is often accompanied by severe abdominal or back
      pain. It's the first study to evaluate the analgesic effect of electroacupuncture
      on pancreatic cancer pain. A randomized controlled trial compared
      electroacupuncture with control acupuncture using the placebo needle. METHODS:
      Sixty patients with pancreatic cancer pain were randomly assigned to the
      electroacupuncture group (n = 30) and the placebo control group (n = 30).
      Patients were treated on Jiaji (Ex-B2) points T8-T12 bilaterally for 30 min once
      a day for 3 days. Pain intensity was assessed with numerical rated scales (NRS)
      before the treatment (Baseline), after 3 treatments, and 2 days follow-up.
      RESULTS: Baseline characteristics were similar in the two groups. After 3
      treatment, pain intensity on NRS decreased compared with Baseline (-1.67, 95%
      confidence interval [CI] -1.46 to -1.87) in the electroacupuncture group; there
      was little change (-0.13, 95% CI 0.08 to -0.35) in control group; the difference
      between two groups was statistically significant (P < 0.001). Follow-up also
      found a significant reduction in pain intensity in the electroacupuncture group
      compared with the control group (P < 0.001). CONCLUSIONS: Electroacupuncture was
      an effective treatment for relieving pancreatic cancer pain.

PMID- 24280576
TI  - The heparin-binding protein interactome in pancreatic diseases.
AB  - BACKGROUND: The cellular microenvironment plays an important role in the
      regulation of homoeostasis and is a source of potential biomarkers and drug
      targets. In a genome-wide analysis the extracellular proteins that bind to
      heparin (HBPs) have been shown to form highly modular and interconnected
      extracellular protein regulatory networks. Using a systems biology approach, we
      have investigated the role of HBP networks in the normal pancreas and pancreatic
      digestive diseases. METHODS: Lists of mRNAs encoding for HBPs associated with the
      normal pancreas (NP), acute pancreatitis (AP), chronic pancreatitis (CP) and
      pancreatic ductal adenocarcinoma (PDAC) were obtained using public databases and
      publications. Networks of the putative protein interactomes derived from mRNA
      expression data of HBPs were built and analysed using cluster analysis, gene
      ontology term enrichment and canonical pathways analysis. RESULTS: The
      extracellular heparin-binding putative protein interactomes in the pancreas were
      better connected than their non heparin-binding counterparts, having higher
      clustering coefficients in the normal pancreas (0.273), acute pancreatitis
      (0.457), chronic pancreatitis (0.329) and pancreatic ductal adenocarcinoma
      (0.269). 'Hepatic Fibrosis/Hepatic Stellate Cell Activation' appears to be a
      significant canonical pathway in pancreatic homoeostasis in health and disease
      with a large number of important HBPs. CONCLUSIONS: Our analyses clearly
      demonstrate that HBPs form disease-specific and highly connected networks that
      can be explored for potential biomarkers and as collective drug targets via the
      modification of heparin binding properties.

PMID- 24280577
TI  - Pancreatic injuries in earthquake victims: what have we learnt?
AB  - OBJECTIVE: To analyze the clinical characteristic and management of patients with
      pancreatic injuries from the Wen-Chuan and Lu-Shan earthquakes. METHODS: We
      retrospectively reviewed 39,784 patients from the Wen-Chuan earthquake and 1489
      from the Lu-Shan earthquake. The demographics, clinical data, treatment
      strategies, and outcomes of patients with pancreatic injuries were recorded and
      compared between survivors of the two earthquakes. RESULTS: Pancreatic injury
      occurred only in a small proportion (0.2%) in patients with trauma on admission,
      and most (61%) patients had Grades I-II pancreatic injuries. Blunt trauma was the
      leading cause of pancreatic trauma. Most patients (95%) suffered multiple
      injuries, of which chest injuries (61%) were the most common. Elevated serum
      amylase levels were observed in 50 (86%) of 58 patients, and computed tomography
      (CT) identified pancreatic injuries in 32 (80%) of 40 patients. A significantly
      higher rate (p = 0.043) of pancreatic complication was present in patients with
      Grade III and IV injuries (38%) than in those with Grade I and II injuries (18%).
      Forty patients were initially treated by conservative management with 6 (15%)
      requiring delayed operations. Four (67%) pancreatic complications and 2 (33%)
      deaths occurred in patients with delayed operations. CONCLUSIONS: Repeated serum
      amylase analysis, CT, and laparoscopic exploration were reliable diagnostic
      modalities to diagnose pancreatic injury. Conservative management was safe in
      patients with Grade I and II injuries. Delayed operation, especially for Grade
      III patients, resulted in increased morbidity and mortality.

PMID- 24280578
TI  - Cryopreserved mouse pancreatic acinar cells from long-term explant outgrowth
      cultures maintain their secretory phenotype after thawing.
AB  - BACKGROUND/OBJECTIVES: We recently reported an explant outgrowth culture method
      for obtaining functionally competent mouse pancreatic acinar cells for long-term
      in vitro purposes. The aim of the present study was to explore the possibility of
      cryostoring these cells without loss of functional differentiation. METHODS:
      Acinar cells prepared by the explant outgrowth method were cryopreserved using a
      DMSO-based protocol and stored in liquid nitrogen for 4 weeks. The following
      characteristics were compared in cryopreserved and parallel non-frozen cell
      preparations: cell viability and recovery, amylase content in viable cells before
      culture, basal and stimulated amylase release in culture and the ability of the
      cells to form glandular structures in Matrigel. RESULTS: Immediate post-thaw
      viability of the cells was similar to that of freshly isolated cells.
      Approximately 53% of viable cells frozen were recovered after thawing.
      Intracellular amylase content was identical in frozen and non-frozen cells.
      Cryopreserved cells maintained their ability to secrete amylase and to respond to
      caerulein stimulation in 4-day secondary cultures. They also were observed to
      form amylase-expressing glandular structures in three-dimensional cultures in
      Matrigel in a similar manner as non-frozen cells. CONCLUSIONS: This study shows
      that pancreatic acinar cells can be cryopreserved for long-term storage in liquid
      nitrogen without dedifferentiation. Successful cryopreservation helps to refine
      the experimental use of primary acinar cells by enabling their banking for on
      demand utilization.

PMID- 24280579
TI  - Dilated papilla with mucin extrusion is a potential predictor of acute
      pancreatitis associated with intraductal papillary mucinous neoplasms of
      pancreas.
AB  - BACKGROUND/OBJECTIVES: As intraductal papillary mucinous neoplasm (IPMN) of the
      pancreas is associated with acute pancreatitis (AP) in some cases, predicting the
      risk of pancreatitis is as important as predicting the risk of malignancy in IPMN
      cases. In this study, we attempted to clarify the characteristics of IPMN
      associated with AP, compared to those of IPMN not associated with AP. METHODS:
      From January 2006 to March 2013, data from 88 patients who underwent surgery for
      IPMN were retrospectively investigated and analyzed. We evaluated clinical and
      pathological variables of each patient and compared patients with IPMN with AP to
      those without AP. Furthermore, we presented representative cases of mild and
      severe pancreatitis caused by IPMN. RESULTS: Overall, 12 of 88 patients with IPMN
      (13.6%) had AP. Seven of the 12 patients had a single episode of AP, whereas the
      remaining 5 patients were diagnosed with IPMN with repeated AP. Ten of 12
      patients with AP were diagnosed with mild AP and the remaining 2 with severe AP.
      Regarding clinical findings, the proportion of dilated papilla with mucin
      extrusion was significantly higher in patients with IPMN with AP than in those
      without AP (p = 0.035). Histological findings indicated that the proportion of
      intestinal-subtype IPMN was significantly higher in patients with IPMN with AP (p
      = 0.013). CONCLUSIONS: AP caused by IPMN derives mostly from intestinal IPMN.
      Dilated papilla with mucin extrusion can be a potential predictor of AP.

PMID- 24280580
TI  - Endoscopic transpapillary pancreatic stenting for internal pancreatic fistula
      with the disruption of the pancreatic ductal system.
AB  - BACKGROUND: Internal pancreatic fistula (IPF) is a well-recognized complication
      of pancreatic diseases. Although there have been many reports concerning IPF, the
      therapy for IPF still remains controversial. We herein report our experiences
      with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its
      validity. METHOD: Six patients with IPF who presented at our department and
      received endoscopic transpapillary pancreatic stent therapy were investigated,
      focusing on the clinical and imaging features as well as treatment strategies,
      the response to therapy and the outcome. RESULTS: All patients were complicated
      with stenosis or obstruction of the main pancreatic duct, and in these cases the
      pancreatic ductal disruption developed distal to the areas of pancreatic
      stricture. The sites of pancreatic ductal disruption were the pancreatic body in
      five patients and the pancreatic tail in one patient. All patients received
      endoscopic stent placement over the stenosis site of the pancreatic duct. Three
      patients improved completely and one patient improved temporarily. Finally, three
      patients underwent surgical treatment for IPF. All patients have maintained a
      good course without a recurrence of IPF. CONCLUSION: Endoscopic transpapillary
      pancreatic stent therapy may be an appropriate first-line treatment to be
      considered before surgical treatment. The point of stenting for IPF is to place a
      stent over the stenosis site of the pancreatic duct to reduce the pancreatic
      ductal pressure and the pseudocyst's pressure.

PMID- 24280581
TI  - A review of splenic pathology in distal pancreatectomies.
AB  - OBJECTIVES: Splenectomy is often performed during distal pancreatectomy for
      malignancy, yet little data exist demonstrating splenic involvement in distal
      pancreatic pathology. METHODS: We retrospectively reviewed 81 distal
      pancreatectomies performed for suspected or known pancreatic malignancies from
      6/1/05 to 7/6/11. Exclusion criteria included metastatic disease, previous
      splenic preserving distal pancreatectomy, or planned en-bloc resection, leaving
      47 cases. Data collected included spleen, hilar lymph node, or splenic vessel
      involvement by malignancy as confirmed by final pathology report. This was
      correlated with preoperative computed tomography (CT). RESULTS: Final pathology
      showed adenocarcinoma in 10 (21%) patients. Three patients with adenocarcinoma
      had invasion of the spleen, splenic vessels or nodes on pathology. The first
      involved the splenic flexure, necessitating en-bloc colon resection. The second
      had splenic artery involvement as identified by CT, but no malignancy within the
      spleen. The third had direct extension to one of 11 peri-splenic nodes with
      significant inflammatory reaction noted intraoperatively. CONCLUSIONS:
      Splenectomy is not mandated for all distal pancreatic tumors, and the spleen can
      be preserved in an overwhelming majority of cases. Pre- and intraoperative
      factors can adequately identify the necessity of splenectomy, and the approach
      should be tailored to individual patients.

PMID- 24280582
TI  - Evidence of pancreatic neuropathy and neuropathic pain in hereditary chronic
      pancreatitis.
AB  - Increased neural density and neural hypertrophy are characteristic features of
      pancreatic neuropathy in chronic pancreatitis. Here, we present the extraordinary
      case of prominent pancreatic neuropathy in a 21-year-old female patient with
      hereditary chronic pancreatitis and intractable pain who underwent total
      pancreatectomy. The histopathological analysis demonstrated remnant pancreatic
      tissue which was only composed of prominent intrapancreatic nerves and fibrosis,
      without any visible remaining functional pancreatic parenchyma. These
      histological alterations, including nerve hypertrophy and increased neural
      density, are known for different aetiologies of chronic pancreatitis, e.g.
      alcoholic, idiopathic and tropic pancreatitis. However, this is the first report
      of a patient with hereditary chronic pancreatitis demonstrating the
      characteristic features of pancreatic neuropathy and neuropathic pain. 

PMID- 24280583
TI  - Pancreatic metastasis from a solitary fibrous tumor of the kidney: a rare cause
      of acute recurrent pancreatitis.
AB  - Solitary fibrous tumors are unusual spindle cell neoplasms that uncommonly
      originate from the kidney. We report a case of a 43-year old male who presented
      with acute recurrent pancreatitis secondary to a mass in the head of the
      pancreas. Endoscopic ultrasound with fine needle aspiration (EUS-FNA) was
      performed. Cytology revealed solitary fibrous tumor of the kidney. This is the
      first reported case of solitary fibrous tumor metastasizing to the pancreas and
      presenting as acute recurrent pancreatitis. 

PMID- 24280584
TI  - Unresectable giant pancreatic neuroendocrine tumor effectively treated by high
      intensity focused ultrasound: a case report and review of the literature.
AB  - Patients with pancreatic neuroendocrine tumors (PNETs) diagnosed at late stage
      are not suitable candidates for surgery. So far, only a limited number of cases
      have been documented in literature about the effectiveness of HIFU, which has
      been more frequently reported to treat pancreatic adenocarcinoma rather than
      PNET. We report herein that a patient with a pancreatic neuroendocrine
      unresectable tumor was effectively treated with serial high-intensity focused
      ultrasound (HIFU) ablation, with no significant side effects detected. Upon
      evaluation, treatment results included: the tendency of tumor shrinkage, pain
      relief, decreased tumor marker levels, and obvious improvements in quality of
      life. Sustained efficacy was observed during a follow-up at 25 months with no
      tumor progression. 

PMID- 24280585
TI  - Plumbagin induces apoptotic and autophagic cell death through inhibition of the
      PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells.
AB  - Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This
      study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on
      A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the
      intracellular level of reactive oxygen species in both cell lines. PLB dose
      dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as
      indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of
      autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced
      apoptosis and autophagy. These findings indicate that PLB initiates both
      apoptosis and autophagy in NSCLC cells through coordinated pathways.

PMID- 24280586
TI  - An in-depth case examination of an exotic dancer's experience of melanotan.
AB  - BACKGROUND: Cultural values placed on tanned skin equating with perceived health
      and attractiveness in the Western world have stimulated the development, sale and
      use of synthetic tanning agents. These agents are synthetic analogues of the
      naturally occurring melanocyte-stimulating hormones (alpha-MSHs) which stimulate
      melanogenesis or pigmentation of the skin. There is a lack of research on
      prevalence of use, user experiences and outcomes, despite evident 'health
      marketability' and diffusion of use via the Internet. METHODS: We present a
      unique, intensive, holistic and exploratory single case study analysis of an
      active user's experiences of synthetic tanning product's labelled as melanotan,
      with rich description of the case's meanings and identities attached to being
      tanned, motives for use, injecting experiences and practices, sourcing routes,
      outcomes and future intentions to use. RESULTS: The case, an exotic dancer, had
      no prior drug injecting experience and did not identify as 'injecting drug user'.
      Introduction to injecting of synthetic tanning products occurred with peer
      assistance. She was conscious of safe injecting practices, which were described
      as not using needles twice, keeping the product refrigerated, disinfecting and
      rotating injecting sites, and using sterilised water to dissolve the product. She
      was aware of synthetic tanning products being unlicensed, unregulated and
      possibly contaminated. She appeared assured in the self-administration of double
      dosage and self-management of nausea with benzodiazepines and by injecting before
      sleep. Experiences of synthetic tanning were positive, with reported feelings of
      enhanced self-confidence and perceived attractiveness grounded in her confidence
      in the product's effectiveness to achieve a desired darkened skin tone. No long
      term or chronic negative outcomes were reported. Development of tolerance and
      awareness of dependence on synthetic tanning agents was described. CONCLUSION: We
      discuss her expert account as it relates to the synthetic tanning product
      outcomes, risk heuristics, sourcing routes and make recommendations for policy.

PMID- 24280587
TI  - Mating-induced endometritis: physiology or pathology?

PMID- 24280588
TI  - Detection of Mycobacterium avium subsp. paratuberculosis in faeces using
      different procedures of pre-treatment for real-time PCR in comparison to culture.
AB  - One of the most relevant aspects in the diagnosis of paratuberculosis (Johne's
      disease) in cattle is the availability of a method for the rapid and sensitive
      detection of Mycobacterium avium subsp. paratuberculosis (MAP) in order to
      facilitate the prompt removal of pathogen-shedding animals from a herd. To meet
      this requirement, methods for pre-treatment of bovine faecal samples and
      subsequent extraction of DNA for detection of MAP by real-time PCR were compared
      with MAP culture results. A total of 116 bovine faecal samples that showed weak
      (64.7%), moderate (18.1%) or strong (17.2%) growth of MAP on solid HEY medium
      were investigated. For PCR, supernatants, sediments or bacterial pellets were
      obtained from faecal samples by pre-treatment before extraction of MAP DNA based
      on silica membranes or magnetic particles. Samples then were tested by MAP IS900
      and ISMav2 real-time PCR with an analytical sensitivity of 6 and 28 genome
      equivalents (GE) per mL, respectively. The best results were obtained by
      including a microfiltration step in the sample pre-treatment in combination with
      silica membrane-based mini-columns or magnetic particles for DNA extraction. This
      approach enhanced the detection rate of MAP in IS900 real-time PCR from 58.6% to
      84.5% using silica membrane mini-columns and from 61.2% to 64.7% using magnetic
      particles. 

PMID- 24280589
TI  - Re-sequencing of mitochondrial genes in a standard rice cultivar Nipponbare.
AB  - BACKGROUND: Genomic sequence of a rice cultivar Nipponbare has been often used as
      a reference sequence since a whole-genomic sequence was first determined in 2005
      by the International Rice Genome Sequencing Project. As for mitochondrial genomic
      sequence of Nipponbare, two groups have deposited their sequences into
      DDBJ/EMBL/GenBank under the accession numbers BA000029 and DQ167400. However,
      there are 19 discrepancies in the nucleotide sequences of 7 genes between
      BA000029 and DQ167400. FINDINGS: We performed PCR to amplify these 7 genes and to
      perform direct sequencing. Nucleotides of the discrepant sites were all identical
      to those in DQ167400.1. The sequence in BA000029.3 is thought to contain
      sequencing errors. CONCLUSION: Nucleotide sequences of the mitochondrial genes in
      BA000029.3 need to be updated using the data in this study when used as a
      reference genome.

PMID- 24280590
TI  - Introns targeted by plant microRNAs: a possible novel mechanism of gene
      regulation.
AB  - BACKGROUND: In plant cells, most microRNAs (miRNAs) perform cleavages of target
      mature mRNAs in the cytoplasm. A recent report of a miRNA pathway involved in DNA
      methylation in the rice nucleus raises the possibility that plant miRNAs could
      cleave intron-containing pre-mRNAs (the precursor of messenger RNAs) located in
      the nucleus. RESULTS: In this study, we searched for the miRNA binding sites
      present within the introns of Arabidopsis (Arabidopsis thaliana) and rice (Oryza
      sativa) genes. All miRNA-intron interactions predicted to result in cleavages
      were validated by using the public degradome sequencing data. As a result, 40
      miRNA-intron pairs involving 25 miRNAs in Arabidopsis and 1912 pairs involving 91
      miRNAs in rice were identified. For several rice genes, not all transcription
      forms (alternative splicing variants) were under similar regulation by specific
      miRNAs. Certain transcripts could escape cleavages due to the absence of intronic
      miRNA binding sites within these sequences. In some instances, specific cleaved
      intron remnants could be converted to double-stranded RNAs (dsRNAs) by RNA
      dependent RNA polymerase 2. These dsRNAs could then be processed into 21- and 24
      nt phased sRNAs by the activity of Dicer-like 1 and 3, respectively. The
      resultant siRNAs have the potential to be incorporated into Argonaute (AGO)
      associated silencing complexes and result in cleavages of target pre-mRNA
      sequences. CONCLUSIONS: A regulatory model, miRNA-targeting of intron-containing
      pre-mRNAs-phased sRNAs-targeting of mature mRNAs is proposed, which further
      expands the potential modes of action of plant miRNAs.

PMID- 24280591
TI  - Prediction of SSVEP-based BCI performance by the resting-state EEG network.
AB  - OBJECTIVE: The prediction of brain-computer interface (BCI) performance is a
      significant topic in the BCI field. Some researches have demonstrated that
      resting-state data are promising candidates to achieve the goal. However, so far
      the relationships between the resting-state networks and the steady-state visual
      evoked potential (SSVEP)-based BCI have not been investigated. In this paper, we
      investigate the possible relationships between the SSVEP responses, the
      classification accuracy of five stimulus frequencies and the closed-eye resting
      state network topology. APPROACH: The resting-state functional connectivity
      networks of the corresponding five stimulus frequencies were created by
      coherence, and then three network topology measures--the mean functional
      connectivity, the clustering coefficient and the characteristic path length of
      each network--were calculated. In addition, canonical correlation analysis was
      used to perform frequency recognition with the SSVEP data. MAIN RESULTS:
      Interestingly, we found that SSVEPs of each frequency were negatively correlated
      with the mean functional connectivity and clustering coefficient, but positively
      correlated with characteristic path length. Each of the averaged network topology
      measures across the frequencies showed the same relationship with the SSVEPs
      averaged across frequencies between the subjects. Furthermore, our results also
      demonstrated that the classification accuracy can be predicted by three averaged
      network measures and their combination can further improve the prediction
      performance. SIGNIFICANCE: These findings indicate that the SSVEP responses and
      performance are predictable using the information at the resting-state, which may
      be instructive in both SSVEP-aided cognition studies and SSVEP-based BCI
      applications.

PMID- 24280593
TI  - EXAMINER executive function battery and neurologic morbidity in pediatric sickle
      cell disease.
AB  - Sickle cell disease (SCD) is blood disorder with a high risk for cerebral
      vascular morbidities that impact neurocognitive functioning. Specific cognitive
      abilities are known to be more sensitive to neurologic effects of SCD than IQ
      scores, yet there is little consensus about which measures to use to assess
      neurocognitive functioning. We evaluated the ability of the Executive Abilities:
      Methods and Instruments for Neurobehavioral Evaluation and Research (EXAMINER)
      Battery to detect neurologic effects in SCD. Thirty-two youth with SCD and sixty
      demographically-matched comparison youth completed the EXAMINER Battery and
      selected tests from the Woodcock-Johnson Tests of Cognitive Ability, 3rd edition
      (WJ-III). Neurologic severity was examined via clinical history for morbidities
      and midsagittal corpus callosum (CC) area. Results indicated cognitive
      performance decreased with increasing neurologic morbidity across all cognitive
      measures; two of four EXAMINER factors were related to CC area. The association
      with clinical history and midsagittal CC area appeared at least as large for the
      Examiner Battery scores as for the WJ-III measures. The Examiner Battery showed
      sensitivity to neurologic history and white matter effects in SCD; this new
      measure compares favorably to established measures of disease-related
      neurocognitive effects, but would benefit from further development.

PMID- 24280592
TI  - The prevalence of diabetes complications and associated risk factors in Pacific
      Islands countries.
AB  - AIM: To determine the prevalence of diabetes complications and associated risk
      factors among people with type 2 diabetes in three Pacific Island countries,
      Nauru, Solomon Islands and Vanuatu. METHODS: This cross-sectional study was
      carried out on a sample of 459 people with diabetes. Subjects were screened for
      complications using a standardised protocol which gathered information on
      demographics, physical and biochemical parameters. RESULTS: Of the 459 subjects,
      47% were female, mean age was 54 years and mean duration of diabetes was eight
      years. The prevalence of diabetes complications was significantly higher in Nauru
      compared with the Solomon Islands and Vanuatu - microalbuminuria 71%, 36% and 51%
      respectively (P<0.001), retinopathy 69%, 40% and 42% respectively (P<0.001), and
      abnormal foot sensation 30%, 23% and 19% respectively (P=0.036). The prevalences
      of hypertension, overweight/obesity and poor glycaemic control were high. The
      percentages of subjects achieving recommended clinical targets were low.
      Microalbuminuria was significantly associated with duration of diabetes,
      hypertension and glycaemic control. Diabetic retinopathy was significantly
      associated with duration of diabetes whereas abnormal foot sensation was
      significantly associated with duration of diabetes and glycaemic control.
      CONCLUSIONS: This study found a high prevalence of diabetes complications and
      associated risk factors, which indicate the need to improve diabetes care and
      strengthen preventive efforts to reduce complications.

PMID- 24280594
TI  - Facultative symbiont Hamiltonella confers benefits to Bemisia tabaci (Hemiptera:
      Aleyrodidae), an invasive agricultural pest worldwide.
AB  - Bacterial symbionts infect most insect species, including important pests such as
      whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), and often exert
      important effects on host ecology. The facultative symbiont Hamiltonella is found
      at high frequencies in the B. tabaci MED (type: Mediterranean-MED) in China. The
      prevalence of this symbiont in natural populations suggests beneficial effects of
      infection or manipulation of host reproduction. To date, however, no empirical
      studies on the biological role of Hamiltonella on the host B. tabaci have been
      reported. Here, we investigated the effects of Hamiltonella infection on the sex
      ratio and several fitness parameters in B. tabaci MED by comparing Hamiltonella
      infected whiteflies with Hamiltonella-free ones. We found that Hamiltonella
      infected whiteflies produced significantly more eggs, exhibited significantly
      higher nymphal survival, faster development times, and larger adult body size in
      comparison with Hamiltonella-free whiteflies, while no evidence of reproductive
      manipulation by Hamiltonella were found in B. tabaci MED. In conclusion,
      Hamiltonella infection substantially enhanced B. tabaci MED performance. This
      beneficial role may, at least partially, explain the high prevalence of
      Hamiltonella in B. tabaci MED populations and may also contribute to their
      effectiveness in spread of the plant pathogens tomato yellow leaf curl virus. 

PMID- 24280595
TI  - Temporal and spatial characterization of mononuclear phagocytes in circulating,
      lung alveolar and interstitial compartments in a mouse model of bleomycin-induced
      pulmonary injury.
AB  - The mononuclear phagocyte system, including circulating monocytes and tissue
      resident macrophages, plays an important role in acute lung injury and fibrosis.
      The detailed dynamic changes of mononuclear phagocytes in the circulating, lung
      alveolar and interstitial compartments in bleomycin-induced pulmonary injury
      model have not been fully characterized. The present study was designed to
      address this issue and analyzed their relationships with pulmonary pathological
      evolution after bleomycin challenge. A total of 100 male C57BL/6 mice were
      randomly divided to receive bleomycin (2.5mg/kg, n=50) or normal saline (n=50)
      via oropharyngeal approach, and were sacrificed on days 1, 3, 7, 14 and 21.
      Circulating monocyte subsets, polarization state of bronchoalveolar lavage fluid
      (BALF)-derived alveolar macrophages (AMphi) and lung interstitial macrophages
      (IMphi, derived from enzymatically digested lung tissue) were analyzed by flow
      cytometry. There was a rapid expansion of circulating Ly6C(hi) monocytes which
      peaked on day 3, and its magnitude was positively associated with pulmonary
      inflammatory response. Moreover, an expansion of M2-like AMphi
      (F4/80+CD11c+CD206+) peaked on day 14, and was positively correlated with the
      magnitude of lung fibrosis. The polarization state of IMphi remained relatively
      stable in the early- and mid-stage after bleomycin challenge, expect for an
      increase of M2-like (F4/80+CD11c-CD206+) IMphi on day 21. These results support
      the notion that there is a Ly6C(hi)-monocyte-directed pulmonary AMphi alternative
      activation. Our result provides a dynamic view of mononuclear phagocyte change in
      three compartments after bleomycin challenge, which is relevant for designing new
      treatment strategies targeting mononuclear phagocytes in this model. 

PMID- 24280596
TI  - Comparative efficacy and adverse effects of the addition of ezetimibe to statin
      versus statin titration in chronic kidney disease patients.
AB  - BACKGROUND AND OBJECTIVES: The recent SHARP trial clearly demonstrated that a
      reduction in low-density lipoprotein (LDL) cholesterol with a daily regimen of
      simvastatin plus ezetimibe safely reduced the incidence of major atherosclerotic
      events in patients with chronic kidney disease (CKD). We aimed to compare the
      efficacy of and adverse effects from statin uptitration versus statin in
      combination with ezetimibe since only a few studies have addressed this question.
      METHODS: This was a randomized, open-label, multicenter trial that included 286
      patients with CKD whose LDL cholesterol levels were not reduced below 120 mg/dl
      despite a minimum dose of statin therapy. Patients received double doses of
      statin or usual statin dose with the addition of ezetimibe 10 mg daily. The
      observation period was 1 year during which time patients were checked regularly
      in clinic for adverse effects as well as for usual laboratory examinations. The
      key prespecified outcome was the incidence of adverse effects, which included
      skeletal muscle complaints, myalgia, muscle weakness, and muscle cramps with and
      without elevated CK levels. Increases in alanine transaminase (ALT) or aspartate
      transaminase (AST) levels >2 times the upper limit of normal (ULN) were
      considered clinically significant adverse effects. RESULTS: Adverse events
      occurred in 9/145 in the combination group and in 24/141 in the statin
      uptitration group (p < 0.01). Moreover, in patients with CKD of stages 3-5, rates
      were 6/58 in the combination group versus 20/52 in the statin uptitration group
      (p < 0.01). No serious adverse effects such as rhabdomyolysis were noted in
      either group. Serum creatinine levels remained essentially unchanged in both
      groups except in CKD stages 4 and 5. Reductions in LDL cholesterol were similar
      between the two groups at the start of and at the end of the study. During the
      study, no atherosclerotic events were reported in either group. CONCLUSION: When
      statin uptitration produces adverse effects such as myopathy, combination therapy
      with ezetimibe is recommended instead of statin alone.

PMID- 24280598
TI  - Patterned cell arrays and patterned co-cultures on polydopamine-modified
      poly(vinyl alcohol) hydrogels.
AB  - Live cell arrays are an emerging tool that expand traditional 2D in vitro cell
      culture, increasing experimental precision and throughput. A patterned cell
      system was developed by combining the cell-repellent properties of polyvinyl
      alcohol hydrogels with the cell adhesive properties of self-assembled films of
      dopamine (polydopamine). It was shown that polydopamine could be patterned onto
      spin-cast polyvinyl alcohol hydrogels by microcontact printing, which in turn
      effectively patterned the growth of several cell types (HeLa, human embryonic
      kidney, human umbilical vein endothelial cells (HUVEC) and prostate cancer). The
      cells could be patterned in geometries down to single-cell confinement, and it
      was demonstrated that cell patterns could be maintained for at least 3 weeks.
      Furthermore, polydopamine could be used to modify poly(vinyl alcohol) in situ
      using a cell-compatible deposition buffer (1 mg mL(-1) dopamine in 25 mM tris
      with a physiological salt balance). The treatment switched the PVA hydrogel from
      cell repellent to cell adhesive. Finally, by combining microcontact printing and
      in situ deposition of polydopamine, patterned co-cultures of the same cell type
      (HeLa/HeLa) and dissimilar cell types (HeLa/HUVEC) were realized through simple
      chemistry and could be studied over time. The combination of polyvinyl alcohol
      and polydopamine was shown to be an attractive route to versatile, patterned cell
      culture experiments with minimal infrastructure requirements and low complexity. 

PMID- 24280597
TI  - Hemodynamic and hormonal patterns of untreated essential hypertension in men and
      women.
AB  - BACKGROUND: Knowledge of hemodynamic factors accounting for the development of
      hypertension should help to tailor therapeutic approaches and improve blood
      pressure control. Few data exist regarding sex differences of hemodynamic factors
      contributing to hypertension progression among patients with untreated
      nondiabetic stage I and II prehypertension (PreHyp) as defined by the Joint
      National Committee-7 guidelines (JNC-7). METHODS: We utilized noninvasive
      impedance cardiography, applanation tonometry and plasma measures of angiotensin
      II, angiotensin (1-7), serum aldosterone, high-sensitivity C-reactive protein (hs
      CRP) and cytokine biomarkers of inflammation to characterize the hemodynamic and
      hormonal profile of 100 patients with untreated hypertension (39 women). RESULTS:
      Despite there being no differences between women and men in terms of office blood
      pressure, heart rate and body mass index, men demonstrated lower values of pulse
      pressure, systemic vascular resistance, brachial artery pulse wave velocity and
      augmentation index. In each of the three hypertension categories, the increased
      blood pressure in men was associated with significant augmentations in stroke
      volume and cardiac output compared with women. Sex-related hemodynamic
      differences were associated in women with higher plasma levels of leptin, hs-CRP,
      plasma angiotensin II and serum aldosterone, and no differences in the serum
      concentrations of cytokinins. In women but not men, hs-CRP correlated with plasma
      concentrations of transforming growth factor beta1 (TGFbeta1) and body weight; in
      addition, plasma TGFbeta1 correlated with levels of serum vascular cell adhesion
      molecule 1. CONCLUSION: The impact of sex differences in the hemodynamic factors
      accounting for the elevation in arterial pressure in subjects with essential
      hypertension has been poorly characterized or this information is not available.
      We suggest that this gap in knowledge may adversely influence choices of drug
      treatment since our study shows for the first time significant differences in the
      hemodynamic and hormonal mechanisms accounting for the increased blood pressure
      in women compared to men.

PMID- 24280599
TI  - [Genetics - an innovative medical specialty of the future].

PMID- 24280600
TI  - [Behcet disease].

PMID- 24280602
TI  - [Basic aspects of medical genetics].
AB  - The human genome consists of 23 pairs of chromosomes that contain 20 000-25 000
      genes. Genetic disorders can be caused by different mechanisms, and therefore the
      confirmation of a suspected diagnosis requires knowledge of the underlying
      defect, so that the correct test can be applied. Monogenic diseases are caused by
      disturbances in a single gene, and currently only targeted diagnostic testing is
      available following a specific clinical suspicion. Chromosomal disorders usually
      involve multiple genes, so that the symptoms are often less specific. Specialists
      in Medical Genetics FMH are trained in creating a clinical genetic differential
      diagnosis, requesting the according laboratory test, interpretating the results
      and providing expert genetic counseling in presymptomatic and prenatal diagnosis.
      In Switzerland, specific legal principles and ethical guidelines must be taken
      into account. 

PMID- 24280603
TI  - [Intellectual disability - a frequent reason for referral to medical genetics].
AB  - Mental retardation affects about 2-3% of the population and is often associated
      with comorbidities. So far, more than 450 different medical conditions are known
      with mental retardation as a sign and it is assumed that there are many more yet
      to be defined. The diagnosis of the underlying entity allows for a few specific
      optimization of cognitive function, but usually improves the treatment of
      comorbidities. Furthermore, the detection of the underlying genetic defect allows
      the specification of the risk of recurrence and enables prenatal diagnosis for
      future pregnancies of persons at risk in the family. Recent findings suggest that
      especially in diseases that are associated with defective synaptic signal
      transduction may be targeted by specific drugs for improvement of cognitive
      performance in the near future. 

PMID- 24280604
TI  - [Genetic diagnostics of cancer diseases].
AB  - Cancer is caused by genetic alterations, but only 10% of the cancer diseases are
      inherited. The probability for an individual or a family of having inherited
      cancer, individual consequences of the respective results of genetic testing, as
      well as its costs and reimbursement by the health insurance must be addressed by
      expert genetic counseling which at-risk requires special expertise.
      Identification of a germline mutation which may predispose to a variety of
      different cancer types allows determination of an individual's specific life time
      risk in symptomatic as well as in a-symptomatic family members. Identification of
      the underlying defective gene in heritable cancer disorders also enables
      optimized preventive and novel therapeutic approaches specifically targeting the
      underlying molecular pathomechanisms. 

PMID- 24280605
TI  - [Marfan syndrome and related connective tissue disorders].
AB  - Marfan syndrome is an autosomal dominantly inherited connective tissue disorder
      with a prevalence of approximately 1:5000 people. Typical manifestations affect
      the cardiovascular system, eyes, skeleton, lungs, skin and dura mater. Most
      patients have a so-called marfanoid habitus with tall stature, long and narrow
      limbs, a long and narrow head shape and other skeletal abnormalities. Of
      particular medical importance are the possible complications such as severe
      scoliosis or pectus excavatum, spontaneous pneumothorax, retinal detachment, or
      an acute glaucoma evoked by lens luxation. However, the most dangerous
      complication is acute dissection of the ascending aorta, which is usually the
      result of a slowly progressive aortic dilatation. With the introduction of
      therapies the average life expectancy of previously just 32 years could be raised
      to above 60 years. 

PMID- 24280607
TI  - [Carpal tunnel syndrome: steroid injections have a short-term effect, but do not
      prevent operations].

PMID- 24280608
TI  - [N-acetylcysteine reduces exacerbation frequency in COPD].

PMID- 24280613
TI  - A general method for the separation of triphenylphosphine oxide and reaction
      products using high performance countercurrent chromatography.
AB  - A standardised separation methodology was developed for the purification of crude
      reaction mixtures containing triphenylphosphine oxide (TPPO) using high
      performance countercurrent chromatography (HPCCC). A solvent system consisting of
      hexane/ethyl acetate/methanol/water (5:6:5:6) was used in 1 column volume elution
      extrusion mode. The HPCCC methodology was compared with classical RP HPLC
      purification using a set of 12 representative Mitsunobu reaction mixtures. HPCCC
      was seen to yield a 65% increase in the average recovery of the target component
      whilst providing similar final target purities to those obtained by HPLC. By
      eliminating the need for method development for individual samples, the HPCCC
      methodology described within provides a simple and efficient means for the
      purification of the entire family of TPPO-containing reaction products. 

PMID- 24280614
TI  - Development of a C(60)-fullerene bonded open-tubular capillary using a
      photo/thermal active agent for liquid chromatographic separations by pi-pi
      interactions.
AB  - This short communication describes a newly developed open-tubular capillary which
      was coated with C60-fullerene by a covalent bonding via a photo/thermal active
      agent. We utilized perfluorophenyl azide (PFPA) as an active agent, which can be
      used for the "photo click" coupling of the carbon materials. The inner wall of a
      fused silica capillary was treated with silane conjugated PFPA, and then C60
      fullerene was chemically modified by a photoreaction or a thermal reaction.
      Through evaluations of the capillaries by liquid chromatography, the separation
      characteristics of three polycyclic aromatic hydrocarbons (PAHs) were confirmed
      in both capillaries. With comparison of the retention behavior to a commonly used
      C18 column, the prepared capillaries showed the specific separation ability based
      on the pi-pi stacking by C60-fullerene. The capillary prepared by the thermal
      reaction provided the base line separation of phenanthrene, triphenylene, and
      benz[a]pyrene within 3min at 18.8cm capillary length. 

PMID- 24280615
TI  - Ultra(high)-pressure liquid chromatography-electrospray ionization-time-of-flight
      ion mobility-high definition mass spectrometry for the rapid identification and
      structural characterization of flavonoid glycosides from cauliflower waste.
AB  - In this paper, a strategy for the detection and structural elucidation of
      flavonoid glycosides from a complex matrix in a single chromatographic run using
      U(H)PLC-ESI-IMS-HDMS/MS(E) is presented. This system operates using alternative
      low and high energy voltages that is able to perform the task of conventional
      MS/MS in a data-independent way without re-injection of the sample, which saves
      analytical time. Also, ion mobility separation (IMS) was employed as an
      additional separation technique for compounds that are co-eluting after U(H)PLC
      separation. First, the fragmentation of flavonoid standards were analyzed and
      criteria was set for structural elucidation of flavonoids in a plant extract.
      Based on retention times, UV spectra, exact mass, and MS fragment
      characteristics, such as abundances of daughter ions and the presence of radical
      ions ([Y0-H](-)), a total 19 flavonoid glycosides, of which 8 non-acylated and 11
      acylated, were detected and structurally characterized in a cauliflower waste
      extract. Kaempferol and quercetin were the main aglycones detected while sinapic
      and ferulic acid were the main phenolic acids. C-glycosides were also found
      although their structure could not be elucidated. The proposed method can be used
      as a rapid screening test for flavonoid identification and for routine analysis
      of plant extracts, such as these derived from cauliflower waste. The study also
      confirms that agroindustrial wastes, such as cauliflower leaves, could be seen as
      a valuable source of different bioactive phenolic compounds. 

PMID- 24280616
TI  - Factors affecting the formation of iodo-trihalomethanes during oxidation with
      chlorine dioxide.
AB  - Effects of water characteristics, reaction time, temperature, bromide and iodide
      ion concentrations, oxidant doses, and pH on formation of iodinated
      trihalomethanes (I-THM) during oxidation of iodide-containing water with chlorine
      dioxide (ClO2) were investigated. Among the water samples collected from ten
      water sources, iodoform (CHI3) was the predominant I-THM and trace amount of
      chlorodiiodomethane (CHClI2) was occasionally found. CHI3 yields correlated
      moderately with specific UV absorbance (SUVA) (R(2)=0.79), indicating that
      hydrophobic aromatic content were important precursors. Longer reaction time led
      to continued formation of CHI3. I-THM containing bromide was also found in waters
      containing both bromide and iodide, but CHI3 was dominant. The formation of CHI3
      was higher at 25 degrees C than 5 degrees C and 35 degrees C. CHI3 formation
      showed an increase followed by a decrease trend with increasing ClO2 doses and
      iodide concentrations and the highest yields occurred at iodide to ClO2 molar
      ratios of 1-2. pH 8 resulted in the highest CHI3 formation. It should be noted
      that a high iodide concentration was spiked to waters before adding ClO2 and the
      results may not reflect the formation yields of iodinated THMs in real
      conditions, but they provide information about formation trend of I-THM during
      oxidation of ClO2. 

PMID- 24280617
TI  - Comparison of microneedle fractional radiofrequency therapy with intradermal
      botulinum toxin a injection for periorbital rejuvenation.
AB  - BACKGROUND: For periorbital rejuvenation, injection of botulinum toxin A (BoNT/A)
      is known to improve both static as well as dynamic wrinkles. A microneedle
      fractional radiofrequency (MFR) device was recently developed and is a novel and
      promising tool. OBJECTIVE: This study compares the effects of these two treatment
      modalities on periorbital static wrinkles and lines. METHODS: Twelve healthy
      women aged 20-59 years with periorbital wrinkles participated in this study. Each
      patient received one session of intradermal injection of BoNT/A on the left
      periorbital area and three sessions of MFR on the right. Clinical improvement,
      skin elasticity and subjective satisfaction were evaluated at every visit
      (baseline, 3, 6 and 18 weeks). RESULTS: BoNT/A injection showed superior effects
      at 3 and 6 weeks. However, the MFR device showed better improvement at 18 weeks.
      In skin biopsies, the expression of procollagen 3 and elastin was increased on
      the MFR side compared to the untreated skin and the BoNT/A injection side. The
      patient satisfaction surveys at 3 weeks showed better satisfaction on the BoNT/A
      treatment side compared to the MFR treatment side. At 18 weeks, there were no
      significant differences in patient satisfaction between the two sides.
      CONCLUSION: BoNT/A injection rapidly improved periorbital wrinkles, but the
      effect decreased up to week 18. Compared to BoNT/A injection, MFR therapy showed
      gradual and long-term improvement in periorbital rejuvenation.

PMID- 24280618
TI  - Reduced pain inhibition is associated with reduced cognitive inhibition in
      healthy aging.
AB  - The analgesic effect of heterotopic noxious counter-stimulation (HNCS; "pain
      inhibits pain") has been shown to decrease in older persons, while some
      neuropsychological studies have suggested a reduction in cognitive inhibition
      with normal aging. Taken together, these findings may reflect a generalized
      reduction in inhibitory processes. The present study assessed whether the decline
      in the efficacy of pain inhibition processes is associated with decreased
      cognitive inhibition in older persons. Healthy young (18-46 years old; n=21) and
      older (56-75 years old; n=23) adult volunteers participated in one experimental
      session to assess the effect of HNCS (cold pain applied on the left forearm) on
      shock pain and RIII reflex induced by transcutaneous electrical stimulation of
      the right sural nerve. In the same session, participants also performed a
      modified Stroop task, including a target condition requiring the frequent
      switching between inhibition and no inhibition of the meaning of color words. The
      analgesic effect induced by HCNS was significantly smaller in older participants
      for both shock-pain ratings (P<0.001) and RIII-reflex amplitude (P<0.05). The
      Stroop effect was significantly larger in elderly participants in the inhibition
      trials of the switching condition. Increased cognitive interference (ie, larger
      Stroop effect) correlated with smaller inhibition of the RIII reflex by HNCS
      across groups (r=-.34, P=0.025). This association was independent from the age
      related slowing observed in control reading and naming tasks. These results
      suggest a generalized age-related reduction in inhibitory processes affecting
      both executive functions and cerebrospinal processes involved in the regulation
      of pain-related responses induced by competing nociceptive threats.

PMID- 24280619
TI  - Gastrointestinal HCO3- transport and epithelial protection in the gut: new
      techniques, transport pathways and regulatory pathways.
AB  - The concept of a protective alkaline gastric and duodenal mucus layer is a
      century old, yet it is amazing how much new information on HCO3(-) transport
      pathways has emerged recently, made possible by the extensive utilization of gene
      deleted and transgenic mice and novel techniques to study HCO3(-) transport. This
      review highlights recent findings regarding the importance of HCO3(-) for mucosal
      protection of duodenum and other gastrointestinal epithelia against luminal acid
      and other damaging factors. Recently, methods have been developed to visualize
      HCO3(-) transport in vivo by assessing the surface pH in the mucus layer, as well
      as the epithelial pH. New information about HCO3(-) transport pathways, and
      emerging concepts about the intricate regulatory network that governs duodenal
      HCO3(-) secretion are described, and new perspectives for drug therapy discussed.

PMID- 24280620
TI  - Influence of leaching conditions for ecotoxicological classification of ash.
AB  - The Waste Framework Directive (WFD; 2008/98/EC) states that classification of
      hazardous ecotoxicological properties of wastes (i.e. criteria H-14), should be
      based on the Community legislation on chemicals (i.e. CLP Regulation 1272/2008).
      However, harmonizing the waste and chemical classification may involve drastic
      changes related to choice of leaching tests as compared to e.g. the current
      European standard for ecotoxic characterization of waste (CEN 14735). The primary
      aim of the present study was therefore to evaluate the influence of leaching
      conditions, i.e. pH (inherent pH (~10), and 7), liquid to solid (L/S) ratio (10
      and 1000 L/kg) and particle size (<4 mm, <1 mm, and <0.125 mm), for subsequent
      chemical analysis and ecotoxicity testing in relation to classification of
      municipal waste incineration bottom ash. The hazard potential, based on either
      comparisons between element levels in leachate and literature toxicity data or
      ecotoxicity testing of the leachates, was overall significantly higher at low
      particle size (<0.125 mm) as compared to particle fractions <1mm and <4mm, at pH
      10 as compared to pH 7, and at L/S 10 as compared to L/S 1000. These results show
      that the choice of leaching conditions is crucial for H-14 classification of ash
      and must be carefully considered in deciding on future guidance procedures in
      Europe.

PMID- 24280621
TI  - Policy implementation of the Republic Act (RA) No. 9003 in the Philippines: a
      case study of Cebu City.
AB  - Municipal Solid Waste Management (MSWM) is considered to be one of the most
      serious environmental issues in the Philippines. The annual waste generation was
      estimated at 10.6 million tonnes in 2012 and this is expected to double in 2025.
      The Republic Act (RA) No. 9003, widely known as the Ecological Solid Waste
      Management Act of 2000, provides the required policy framework, institutional
      mechanisms and mandate to the Local Government Units (LGUs) to achieve 25% waste
      reduction target through establishing an integrated solid waste management plan
      based on the 3Rs (reduce, reuse and recycling). Although the initial impact of
      the LGUs is still very limited in implementing the national mandate, this article
      highlights the successful experiences of Cebu, the second largest city in the
      Philippines, in reducing its MSW generation by more than 30% in the past three
      years. This study also explores the implementation process, innovative actions
      taken by the Cebu City Government in implementing the national mandate at local
      level and identifies the factors that influence the policy implementation. The
      findings suggest that the impacts of the national mandate can be achieved if the
      LGUs have the high degree of political commitment, planning and development of
      effective local strategies in a collaborative manner to meet with local
      conditions, partnership building with other stakeholders, capacity development,
      adequate financing and incentives, and in the close monitoring and evaluation of
      performance. 

PMID- 24280622
TI  - Anaerobic co-digestion of swine and poultry manure with municipal sewage sludge.
AB  - The anaerobic digestion of municipal sewage sludge (SS) with swine manure (SM)
      and poultry manure (PM) was undertaken. It was found that a mixture of sewage
      sludge with a 30% addition of swine manure gave around 400 dm(3)/kg VS of biogas,
      whereas the maximal biogas yield from ternary mixture (SS:SM:PM=70:20:10 by
      weight) was only 336 dm(3)/kg VS. An inhibition of methanogenesis by free ammonia
      was observed in poultry manure experiments. The anaerobic digestion was
      inefficient in pathogen inactivation as the reduction in the number of E. coli an
      Enterobacteriaceae was only by one logarithmic unit. A substantial portion of
      pathogens was also released into the supernatant.

PMID- 24280623
TI  - In vivo testing of a 3D bifurcating microchannel scaffold inducing separation of
      regenerating axon bundles in peripheral nerves.
AB  - Artificial nerve guidance channels enhance the regenerative effectiveness in an
      injured peripheral nerve but the existing design so far has been limited to basic
      straight tubes simply guiding the growth to bridge the gap. Hence, one of the
      goals in development of more effective neuroprostheses is to create bidirectional
      highly selective neuro-electronic interface between a prosthetic device and the
      severed nerve. A step towards improving selectivity for both recording and
      stimulation have been made with some recent in vitro studies which showed that
      three-dimensional (3D) bifurcating microchannels can separate neurites growing on
      a planar surface and bring them into contact with individual electrodes. Since
      the growing axons in vivo have the innate tendency to group in bundles surrounded
      by connective tissue, one of the big challenges in neuro-prosthetic interface
      design is how to overcome it. Therefore, we performed experiments with 3D
      bifurcating guidance scaffolds implanted in the sciatic nerve of rats to test if
      this new channel architecture could trigger separation pattern of ingrowth also
      in vivo. Our results showed that this new method enabled the re-growth of
      neurites into channels with gradually diminished width (80, 40 and 20 um) and
      facilitated the separation of the axonal bundles with 91% success. It seems that
      the 3D bifurcating scaffold might contribute towards conveying detailed neural
      control and sensory feedback to users of prosthetic devices, and thus could
      improve the quality of their daily life.

PMID- 24280624
TI  - Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by
      albumin independent of ERK1/2 signaling.
AB  - BACKGROUND: The cannabinoid receptor type 2 (CB2) is reduced in podocytes of
      animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2
      ameliorating albuminuria in animals. As albuminuria also is due to proximal
      tubule dysfunction, the aim of this study is to investigate tubular expression of
      CB2 under diabetic conditions in addition to the cell signaling pathways that
      underlie these changes. METHODS: We characterized total CB2 protein in diabetic
      animals and in Human Kidney 2 (HK2) cells exposed to elevated albumin and
      glucose, the levels of CB2 mRNA and protein. We also used latrunculin to
      determine if internalization of albumin was required to regulate CB2 levels.
      Finally, we characterized the levels of active and total AKT, ERK1/2 and p38 in
      response to albumin. RESULTS: There were no changes to CB2 expression in kidney
      lysate from diabetic rats. In HK2 cells, expression of CB2 was unaltered
      following exposure to high glucose. High albumin treatment alone and in
      combination with high glucose, resulted in a significant reduction in CB2
      receptor mRNA expression at 6 and 18 hours. CB2 protein expression was reduced at
      6 and 24 hours, in high albumin and in combination with high glucose.
      Internalization of albumin was required to regulate CB2 levels, and inhibition of
      ERK1/2, did not rescue the loss of CB2 in response to albumin. CONCLUSION: We
      have demonstrated that internalization of albumin is required to reduce CB2 mRNA
      and protein expression in proximal tubules in vitro. Consequently, altered
      expression of CB2 in both the podocytes and tubules may contribute to the
      albuminuria observed in T2DM.

PMID- 24280625
TI  - Roles of plant growth regulators on yield, grain qualities and antioxidant enzyme
      activities in super hybrid rice (Oryza sativa L.).
AB  - BACKGROUND: Plant growth regulators play important roles in plant growth and
      development, but little is known about roles of plant growth regulators in yield,
      grain qualities and antioxidant enzyme activities in super hybrid rice. In this
      study, gibberellic acid(GA3), paclobutrazol (PBZ), 6-Benzylaminopurine(6-BA)
      treatments and distilled water (control) were sprayed to two hybrid rice
      cultivars (Peizataifeng and Huayou 86) at the heading stage in the field
      experiments in both early and late season in 2007. Treatments were arranged in a
      split-plot design with four replications. Cultivars treatments with two newly
      developed super hybrid rice Peizataifeng and Huayou86 were the main plots and
      plant growth regulators treatments were the subplots. Subplot treatments included
      (1) plots sprayed with distilled water(CK), (2) plots sprayed with 20 mg L-1 GA3
      prepared using 95% ethanol as surfactant(GA3), (3) plots sprayed with 50 mg L-1
      PBZ(PBZ), (4) plots sprayed with 30 mg L-1 6-BA(6-BA). RESULTS: Spraying PBZ with
      50 mg L-1 or 6-BA with 30 mg L-1 at the heading stage could increase the number
      of spikelets per panicle, seed setting rate and grain yields in Peizataifeng and
      Huayou86 in both seasons. PBZ treatment also significantly improved head rice
      rate and amylose content in Peizataifeng and Huayou86 in early season.
      Furthermore, it was observed that spraying PBZ or 6-BA could increase super oxide
      dismutase (SOD) and peroxidase (POD) activities, decrease accumulation of
      malendialdehyde (MDA) in flag leaves at the late growth stage. CONCLUSIONS:
      Application of PBZ or 6-BA partially alleviated the detrimental effects of rice
      senescence by modulating the activity of enzymatic antioxidants, and improving
      antioxidant system, which helped in sustaining plant growth. Therefore, spraying
      PBZ with 50 mg L-1 or 6-BA with 30 mg L-1 at the heading stage could increase
      grain yields and improve grain qualities in the two super hybrid rice.

PMID- 24280626
TI  - Biomechanical analyses of static and dynamic fixation techniques of retrograde
      interlocking femoral nailing using nonlinear finite element methods.
AB  - Femoral shaft fractures can be treated using retrograde interlocking nailing
      systems; however, fracture nonunion still occurs. Dynamic fixation techniques,
      which remove either the proximal or distal locking screws, have been used to
      solve the problem of nonunion. In addition, a surgical rule for dynamic fixation
      techniques has been defined based on past clinical reports. However, the
      biomechanical performance of the retrograde interlocking nailing systems with
      either the traditional static fixation technique or the dynamic fixation
      techniques has not been investigated by using nonlinear numerical modeling. Three
      dimensional nonlinear finite element models were developed, and the implant
      strength, fixation stability, and contact area of the fracture surfaces were
      evaluated. Three types of femoral shaft fractures (a proximal femoral shaft
      fracture, a middle femoral shaft fracture, and a distal femoral shaft fracture)
      fixed by three fixation techniques (insertion of all the locking screws, removal
      of the proximal locking screws, or removal of the distal locking screws) were
      analyzed. The results showed that the static fixation technique resulted in
      sufficient fixation stability and that the dynamic fixation techniques decreased
      the failure risk of the implant and produced a larger contact area of the
      fracture surfaces. The outcomes of the current study could assist orthopedic
      surgeons in comprehending the biomechanical performances of both static and
      dynamic fixation techniques. In addition, the surgeons could also select a
      fixation technique based on the specific patient situation using the numerical
      outcomes of this study. 

PMID- 24280627
TI  - Evaluation of a haptics-based virtual reality temporal bone simulator for anatomy
      and surgery training.
AB  - INTRODUCTION: Virtual reality simulation training may improve knowledge of
      anatomy and surgical skills. We evaluated a 3-dimensional, haptic, virtual
      reality temporal bone simulator for dissection training. METHODS: The subjects
      were 7 otolaryngology residents (3 training sessions each) and 7 medical students
      (1 training session each). The virtual reality temporal bone simulation station
      included a computer with software that was linked to a force-feedback hand
      stylus, and the system recorded performance and collisions with vital anatomic
      structures. Subjects performed virtual reality dissections and completed
      questionnaires after the training sessions. RESULTS: Residents and students had
      favorable responses to most questions of the technology acceptance model (TAM)
      questionnaire. The average TAM scores were above neutral for residents and
      medical students in all domains, and the average TAM score for residents was
      significantly higher for the usefulness domain and lower for the playful domain
      than students. The average satisfaction questionnaire for residents showed that
      residents had greater overall satisfaction with cadaver temporal bone dissection
      training than training with the virtual reality simulator or plastic temporal
      bone. For medical students, the average comprehension score was significantly
      increased from before to after training for all anatomic structures. Medical
      students had significantly more collisions with the dura than residents. The
      residents had similar mean performance scores after the first and third training
      sessions for all dissection procedures. DISCUSSION: The virtual reality temporal
      bone simulator provided satisfactory training for otolaryngology residents and
      medical students.

PMID- 24280628
TI  - Identifying essential genes/reactions of the rice photorespiration by in silico
      model-based analysis.
AB  - BACKGROUND: Photorespiration, a highly wasteful process of energy dissipation,
      depresses the productivity of C3 plants such as rice (Oryza sativa) under dry and
      hot conditions. Thus, it is highly required to understand the cellular physiology
      and relevant metabolic states under photorespiration using systems approaches,
      thereby devising strategies for improving rice production. FINDINGS: In silico
      model-driven gene deletion analysis was performed on photorespiring leaf cells
      under ambient and stressed environmental conditions using our central metabolic
      network of rice cells. As a result, we identified a number of essential genes for
      the cell growth across various functional pathways such as photorespiratory
      cycle, Calvin cycle, GS-GOGAT cycle and sucrose metabolism as well as certain
      inter-compartmental transporters, which are mostly in good agreement with
      previous experiments. Synthetic lethal (SL) screening was also performed to
      identify the pair of non-essential genes whose simultaneous deletion become
      lethal, revealing the existence of more than 220 pairs of SLs on rice central
      metabolism. CONCLUSIONS: The gene deletion and synthetic lethal analyses
      highlighted the rigid nature of rice photosynthetic pathways and characterized
      functional interactions between central metabolic genes, respectively. The
      biological roles of such reported essential genes should be further explored to
      better understand the rice photorespiration in future.

PMID- 24280629
TI  - [Rhabdomyolisis after a spinning session. Tests to rule out metabolic myopathy].

PMID- 24280630
TI  - Sublingual glyceryl trinitrate and the peripheral thermal responses in normal and
      cold-sensitive individuals.
AB  - Non-freezing cold injury (NFCI) is a prevalent, but largely undiagnosed and
      poorly understood syndrome afflicting many who, as part of their work or leisure,
      expose their extremities to cold temperatures. The long term sequelae of NFCI are
      hyperhidrosis, cold-sensitivity and pain; these can last a lifetime. We tested
      the hypothesis that, in comparison with a placebo, sublingual glyceryl trinitrate
      (GTN) would increase the peripheral microcirculation during and after a mild cold
      challenge of individuals who had not been diagnosed with NFCI, but were cold
      sensitive. Naive participants were categorised into two cohort groups: control
      (n=7) or cold-sensitive (n=6). All participants undertook a standardised two
      minute cold exposure of their right foot while toe skin temperature (Tsk; infra
      red thermograms) and blood flow (toe pad laser Doppler) were measured. GTN
      increased the rate of rewarming and absolute Tsk of the coldest toe after the
      cold challenge in cold-sensitive individuals. GTN also increased the blood flow
      in the great toe during rewarming in some cold-sensitive individuals. We accept
      our hypothesis and suggest that the impairment in the vasodilatory response seen
      in individuals with cold-sensitivity can be overcome by the use of GTN, an
      endothelial-independent NO donor, and thereby improve the rewarming of cooled
      peripheral tissues. 

PMID- 24280631
TI  - Integrating telehealth care-generated data with the family practice electronic
      medical record: qualitative exploration of the views of primary care staff.
AB  - BACKGROUND: Telehealth care is increasingly being employed in the management of
      long-term illness. Current systems are largely managed via "stand-alone"
      websites, which require additional log-ons for clinicians to view their patients'
      symptom records and physiological measurements leading to frustrating delays and
      sometimes failure to engage with the record. However, there are challenges to the
      full integration of patient-acquired data into family physicians' electronic
      medical records (EMR) in terms of reliability, how such data can best be
      summarized and presented to avoid overload to the clinicians, and how clarity of
      responsibility is managed when multiple agencies are involved. OBJECTIVE: We
      aimed to explore the views of primary care clinicians on the acceptability,
      clinical utility, and, in particular, the benefits and risks of integrating
      patient-generated telehealth care data into the family practice EMR and to
      explore how these data should be summarized and presented in order to facilitate
      use in routine care. METHODS: In our qualitative study, we carried out semi
      structured interviews with clinicians with experience of and naive to telehealth
      care following demonstration of pilot software, which illustrated various methods
      by which data could be incorporated into the EMR. RESULTS: We interviewed 20
      clinicians and found 2 overarching themes of "workload" and "safety". Although
      clinicians were largely positive about integrating telehealth care data into the
      EMR, they were concerned about the potential increased workload and safety
      issues, particularly in respect to error due to data overload. They suggested
      these issues could be mitigated by good system design that summarized and
      presented data such that they facilitated seamless integration with clinicians'
      current routine processes for managing data flows, and ensured clear lines of
      communication and responsibility between multiple professionals involved in
      patients' care. CONCLUSIONS: Family physicians and their teams are likely to be
      receptive to and see the benefits of integrating telehealth-generated data into
      the EMR. Our study identified some of the key challenges that must be overcome to
      facilitate integration of telehealth care data. This work particularly underlines
      the importance of actively engaging with clinicians to ensure that systems are
      designed that align well with existing practice data-flow management systems and
      facilitate safe multiprofessional patient care.

PMID- 24280633
TI  - Influence of seminal plasma on leucocyte migration and amount of COX-2 protein in
      the jenny endometrium after insemination with frozen-thawed semen.
AB  - After mating, seminal plasma has an immuno-modulatory effect on the endometrium
      in some mammals. In jennies, achieving conception via artificial insemination
      (AI) with frozen-thawed semen is generally much more difficult than in mares. The
      endometrial inflammatory response is hypothesized to be a contributing factor to
      the lesser fertility. Following a cross-over experimental design, the uterine
      inflammatory response of six jennies was evaluated at 6h after AI with frozen
      thawed semen (deposited in the uterine body) in the presence or absence of
      autologous seminal plasma (+SP or -SP). The endometrial cytology and histology of
      the animals were examined by uterine lavage, uterine swabbing and biopsy. The
      amount of cyclooxygenase-2 (COX-2) protein in endometrial cells was also
      evaluated. As a control (C), the same examinations were made before any AI
      procedure (i.e., when the jennies were in oestrus). Large numbers of
      polymorphonuclear neutrophils (PMN) were observed in the -SP and +SP cytology and
      biopsy samples; more than in the C samples. The -SP samples also had intense COX
      2 labelling; less labelling was detected in the +SP and C samples (no significant
      difference between these latter two types). Thus, while the presence of SP does
      not change the post-AI number of PMNs with regard to that detected in its
      absence, it does reduce COX-2 protein. Further research into the complex mix of
      molecules in SP and its effects during AI might help increase the pregnancy rates
      achieved in jennies. 

PMID- 24280634
TI  - The relationship between body-mass and puberty in young red deer (Cervus elaphus)
      hinds: evidence of early-life effects on permissive live-weight thresholds.
AB  - This study, based on the analysis of growth and reproductive records of 6158
      young red deer hinds, tested the hypothesis that the nutritional environment in
      early life influences the permissive body mass threshold for puberty at around 16
      months of age. Live-weight at 3 months (i.e. weaning weight) was a proxy for
      their nutritional environment between birth and weaning, live-weight at 14 months
      was the indicator of pre-mating body mass, and pregnancy status at 18-19 months
      was a proxy for entry into puberty. Data were obtained for two sub-populations of
      hinds, the commercial stud herds, across four consecutive years. The modelled
      relationships between pre-mating live-weight and the predicted pregnancy rate
      demonstrated between-year variation for the logistic curves for the commercial
      herd for the live-weight range from 50 to 90 kg (P<0.001). For the stud herd, the
      predicted pregnancy rate at any given live-weight did not vary significantly
      between years (P>0.05) and the pregnancy rates for live-weights <90 kg were
      higher than for the commercial herd. The regression of average weaning weight on
      probability of pregnancy showed significant positive associations (P<0.05) at 60
      kg, 70 kg and 80 kg (R(2)=0.513, 0.517 and 0.439, respectively). There were no
      significant regressions at pre-joining live-weights at 90 kg or above (P>0.05).
      The study supports the central hypothesis of early-life influences on the
      permissive body mass threshold for entry into puberty.

PMID- 24280635
TI  - Mechanical characterization of bioprinted in vitro soft tissue models.
AB  - Recent development in bioprinting technology enables the fabrication of complex,
      precisely controlled cell-encapsulated tissue constructs. Bioprinted tissue
      constructs have potential in both therapeutic applications and nontherapeutic
      applications such as drug discovery and screening, disease modelling and basic
      biological studies such as in vitro tissue modelling. The mechanical properties
      of bioprinted in vitro tissue models play an important role in mimicking in vivo
      the mechanochemical microenvironment. In this study, we have constructed three
      dimensional in vitro soft tissue models with varying structure and porosity based
      on the 3D cell-assembly technique. Gelatin/alginate hybrid materials were used as
      the matrix material and cells were embedded. The mechanical properties of these
      models were assessed via compression tests at various culture times, and
      applicability of three material constitutive models was examined for fitting the
      experimental data. An assessment of cell bioactivity in these models was also
      carried out. The results show that the mechanical properties can be improved
      through structure design, and the compression modulus and strength decrease with
      respect to time during the first week of culture. In addition, the experimental
      data fit well with the Ogden model and experiential function. These results
      provide a foundation to further study the mechanical properties, structural and
      combined effects in the design and the fabrication of in vitro soft tissue
      models. 

PMID- 24280636
TI  - Within-field spatial distribution of Megacopta cribraria (Hemiptera: Plataspidae)
      in soybean (Fabales: Fabaceae).
AB  - The recently introduced plataspid Megacopta cribraria (F.) can infest fields of
      soybean (Glycine max (L.) Merrill) in the southeastern United States. Grid
      sampling in four soybean fields was conducted in 2011 and 2012 to study the
      spatial distribution of M. cribraria adults, nymphs, and egg masses. Peak
      oviposition typically occurred in early August, while peak levels of adults
      occurred in mid-late September. The overall sex ratio was slightly biased at 53.1
      +/- 0.2% (SEM) male. Sweep samples of nymphs were biased toward late instars. All
      three life stages exhibited a generally aggregated spatial distribution based on
      Taylor's power law, Iwao's patchiness regression, and spatial analysis by
      distance indices (SADIE). Interpolation maps of local SADIE aggregation indices
      showed clusters of adults and nymphs located at field edges, and mean densities
      of adults were higher in samples taken from field edges than in those taken from
      field interiors. Adults and nymphs were often spatially associated based on
      SADIE, indicating spatial stability across life stages. 

PMID- 24280638
TI  - De novo reciprocal translocation t(5;6)(q13;q34) in cattle: cytogenetic and
      molecular characterization.
AB  - The cytogenetic analysis of a phenotypically normal bull from the Marchigiana
      breed revealed the presence of an abnormal karyotype due to the presence of a
      very long chromosome. This finding, identified in all the metaphases observed,
      was associated with the 2n = 60, XY karyotype, suggesting the presence of a
      reciprocal translocation. RBG- banding analyses identified a de novo reciprocal
      translocation involving BTA5 and BTA6, t(5;6)(q13;q34), while FISH analyses using
      cattle-specific BACs as probes enabled the confirmation and narrowed down the
      breakpoint regions. Array-CGH analysis also established that neither deletions
      nor duplications were present in the regions including the breakpoints, nor were
      they present elsewhere in the genome, confirming the balanced state of the
      translocation.

PMID- 24280639
TI  - Enhancing social cognition by training children in emotion understanding: a
      primary school study.
AB  - We investigated whether training school-age children in emotion understanding had
      a significant effect on their social cognition. Participants were 110 children
      (mean age=7 years 3 months) assigned to training and control conditions. Over a 2
      month intervention program, after the reading of illustrated scenarios based on
      emotional scripts, the training group was engaged in conversations on emotion
      understanding, whereas the control group was simply asked to produce a drawing
      about the story. The training group outperformed the control group on emotion
      comprehension, theory of mind, and empathy, and the positive training outcomes
      for emotion understanding remained stable over 6 months. Implications of the
      findings are discussed.

PMID- 24280640
TI  - Evaluating the status of antiganglioside antibodies in children with Guillain
      Barre syndrome.
AB  - OBJECTIVE: Antiganglioside antibodies have been reported to play a role in the
      pathophysiology of Guillain-Barre syndrome (GBS). METHODS: This case-control
      study was designed to evaluate the status of antiganglioside antibodies in
      children with GBS. The study included 50 patients suffering from GBS as the case
      group and 30 children as the control group. Clinical information such as
      demographic data and recent digestive or respiratory infection (within the last
      month) was collected for all patients, and paraclinical studies including
      cerebrospinal fluid examination and electrophysiology were conducted by a
      subspecialized physician. Anti-GM1, anti-GQ1 and anti-GD1a antibodies were
      measured with ELISA and the EUROLINE method. RESULTS: The mean age of patients in
      the case and control groups was 5.3 +/- 3.8 and 5.4 +/- 3.4 years, respectively.
      With the EUROLINE method, the results obtained for anti-GM1 were significant (p =
      0.007); however, the p values for anti-GQ1a and anti-GQ1b were not significant
      (0.051 vs. 0.94), while with ELISA, comparing all three antibodies in both the
      case and control groups showed statistically significant results, with a p <
      0.05. CONCLUSION: EUROLINE is a new method used to evaluate antibodies in immune
      system diseases, but it is not useful for all antibodies specific to GBS, as the
      analysis was significant with a p value of 0.007 for anti-GM2.

PMID- 24280637
TI  - Disconnected aging: cerebral white matter integrity and age-related differences
      in cognition.
AB  - Cognition arises as a result of coordinated processing among distributed brain
      regions and disruptions to communication within these neural networks can result
      in cognitive dysfunction. Cortical disconnection may thus contribute to the
      declines in some aspects of cognitive functioning observed in healthy aging.
      Diffusion tensor imaging (DTI) is ideally suited for the study of cortical
      disconnection as it provides indices of structural integrity within
      interconnected neural networks. The current review summarizes results of previous
      DTI aging research with the aim of identifying consistent patterns of age-related
      differences in white matter integrity, and of relationships between measures of
      white matter integrity and behavioral performance as a function of adult age. We
      outline a number of future directions that will broaden our current understanding
      of these brain-behavior relationships in aging. Specifically, future research
      should aim to (1) investigate multiple models of age-brain-behavior
      relationships; (2) determine the tract-specificity versus global effect of aging
      on white matter integrity; (3) assess the relative contribution of normal
      variation in white matter integrity versus white matter lesions to age-related
      differences in cognition; (4) improve the definition of specific aspects of
      cognitive functioning related to age-related differences in white matter
      integrity using information processing tasks; and (5) combine multiple imaging
      modalities (e.g., resting-state and task-related functional magnetic resonance
      imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in
      cognitive aging. 

PMID- 24280641
TI  - The role of aquaporin 1 activated by cGMP in myocardial edema caused by
      cardiopulmonary bypass in sheep.
AB  - BACKGROUND/AIMS: Most cardiac procedures involve the use of cardiopulmonary
      bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs
      are isolated. CPB can cause profound alterations V in the homeostasis of
      physiological fluids, which often results in myocardial edema. In our study, we
      used sheep CPB model of in vivo and in vitro to assess the relationship between
      cGMP and AQP1 during CPB. METHODS: ODQ, a specific inhibitor of soluble guanylate
      cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left
      ventricular function of each group was determined by pressure-volume system.
      Water content of myocardial tissue was assessed by dry-wet weight, and
      cardiomyocytes water permeability was also calculated. The concentration of cGMP
      was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1
      were detected by real-time PCR and western blot, respectively. RESULTS: The
      relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12,
      24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold
      at 24 h and 2.18-fold at 48h) compared with each sham group, the protein
      expression of AQP1 also showed a rising trend after CPB. The degree of myocardial
      edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB
      surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7%
      (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition
      of cGMP pathway also can significantly decrease the degree of myocardial edema
      (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function
      in sheep after CPB. Results of in vitro experiments showed the same changing
      trends as in vivo. CONCLUSION: cGMP pathway controls water channels and then
      affects water intake during CPB through an AQP1-mediated pathway.

PMID- 24280642
TI  - Adult female acne. Azelaic acid in the treatment of acne in adult females.
      Introduction.

PMID- 24280643
TI  - Postadolescent acne in females.
AB  - Acne in the adult female often presents as a chronic condition that can have a
      considerable negative psychological, social and emotional impact on the affected
      individual. Estimated prevalence rates of adult female acne vary widely according
      to study type. Case reports and clinical examinations estimate the prevalence of
      clinical acne at 10-12%, while survey estimates of physiological disease states
      are as high as 54%. Two subtypes of adult female acne may be defined according to
      time of onset: 'persistent' and 'late-onset', accounting for approximately 80 and
      20% of cases, respectively. Postadolescent acne is generally mild-to-moderate in
      severity and presents with more inflammatory lesions and fewer comedones compared
      to adolescent acne. Furthermore, the impact of acne on the quality of life is
      often greater in adult females than in younger individuals. Despite these
      important differences, the key principles of acne treatment in the adult female
      do not differ significantly from those of other age groups. However, specific
      characteristics relating to the adult female should be considered when selecting
      a treatment regimen.

PMID- 24280644
TI  - Azelaic acid: Properties and mode of action.
AB  - Acne is a common skin disorder that can be problematic for adults as well as for
      adolescents. It has several key pathophysiological features such as follicular
      hyperkeratosis, elevated Propionibacterium acnes proliferation, and reactive
      inflammation, all of which should be targeted for an optimal outcome. Azelaic
      acid (AzA) has profound anti-inflammatory, antioxidative effects, and is
      bactericidal against a range of Gram-negative and Gram-positive microorganisms as
      well, including antibiotic-resistant bacterial strains. In addition, AzA's
      antikeratinizing effects are inhibitory toward comedones. AzA is effective
      overall in targeting multiple causes of acne and has been proven to be well
      tolerated in numerous clinical trials.

PMID- 24280645
TI  - Azelaic acid in the treatment of acne in adult females: case reports.
AB  - Acne, one of the most common skin problems in dermatological practice, is a
      condition that affects not only adolescents but also adults. While approximately
      80% of cases occurring in adulthood are persistent from teenage years, around 20%
      are described as 'late-onset' disease, appearing for the first time in adulthood.
      The disease can be triggered by hormonal changes (including a change from one
      contraceptive to another), or it can be induced by certain nonhormonal
      medications, emotional stress, and various underlying diseases such as polycystic
      ovary syndrome. In many cases acne becomes a chronic skin condition with
      undulating activity, including improvement and relapse phases, and is often
      experienced as a major psychological burden. It is, therefore, even more
      important to provide an effective as well as a safe and tolerable treatment. The
      spectrum of topical acne treatments has expanded substantially in recent years
      and various topical medications are available, ranging from azelaic acid,
      antibiotics, retinoids and benzoyl peroxide to several fixed combinations of
      these active compounds. The following case collection illustrates how 15% azelaic
      acid gel, as a well-established monotherapy, can be successfully employed to
      treat mild-to-moderate forms of adult female acne.

PMID- 24280646
TI  - The use of botanically derived agents for hyperpigmentation: a systematic review.
AB  - BACKGROUND: Hyperpigmentation disorders are common among those seeking care from
      dermatologists and primary care physicians. The cosmeceutical and natural product
      industries are rapidly growing and many botanical agents are purported to improve
      hyperpigmentation disorders. OBJECTIVE: We sought to review clinical evidence for
      the use of botanical agents in the treatment of hyperpigmentation. METHODS: We
      searched MEDLINE and Embase databases and a total of 26 articles met inclusion
      criteria. Study methodology was analyzed and the reproducibility of the studies
      was graded. RESULTS: Several botanical agents appear promising as treatment
      options but few studies were methodologically rigorous. Several plant extract and
      phytochemicals effectively lighten signs of epidermal melasma and
      hyperpigmentation induced by ultraviolet radiation exposure. Results were mixed
      for treatment of solar lentigines or dermal hyperpigmentation. LIMITATIONS: There
      were few rigorously designed studies; future research will be critical to further
      ascertain the discussed results. CONCLUSIONS: The subtype of hyperpigmentation is
      important for treatment prognosis, with dermal hyperpigmentation less responsive
      to treatment. Botanical extracts may play an integrative role in the treatment of
      hyperpigmentation and further studies that integrate them with standard therapies
      are needed. Side effects, including worsened hyperpigmentation, need to be
      discussed when considering these therapies.

PMID- 24280648
TI  - Introducing glycomics data into the Semantic Web.
AB  - BACKGROUND: Glycoscience is a research field focusing on complex carbohydrates
      (otherwise known as glycans)a, which can, for example, serve as "switches" that
      toggle between different functions of a glycoprotein or glycolipid. Due to the
      advancement of glycomics technologies that are used to characterize glycan
      structures, many glycomics databases are now publicly available and provide
      useful information for glycoscience research. However, these databases have
      almost no link to other life science databases. RESULTS: In order to implement
      support for the Semantic Web most efficiently for glycomics research, the
      developers of major glycomics databases agreed on a minimal standard for
      representing glycan structure and annotation information using RDF (Resource
      Description Framework). Moreover, all of the participants implemented this
      standard prototype and generated preliminary RDF versions of their data. To test
      the utility of the converted data, all of the data sets were uploaded into a
      Virtuoso triple store, and several SPARQL queries were tested as "proofs-of
      concept" to illustrate the utility of the Semantic Web in querying across
      databases which were originally difficult to implement. CONCLUSIONS: We were able
      to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB
      in a single SPARQL query to obtain our target information. We also tested queries
      linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through
      PDB. As a result, we have been able to link proteomics data with glycomics data
      through the implementation of Semantic Web technologies, allowing for more
      flexible queries across these domains.

PMID- 24280647
TI  - Restoration of intrahepatic regulatory T cells through MMP-9/13-dependent
      activation of TGF-beta is critical for immune homeostasis following acute liver
      injury.
AB  - During the acute liver injury, immune responses are provoked into eliciting
      inflammation in the acute phase. In the healing phase, the inflammation is
      terminated for wound healing and restoration of immune homeostasis. In this
      study, we sought to address how regulatory T cells (Tregs) are involved in the
      progression of liver injury and repair. In the acute phase, intrahepatic Tregs
      (CD4(+)FoxP3(+)Helios(+)) diminished promptly through apoptosis, which was
      followed by inflammation and tissue injury. In the healing phase, a new subset of
      Tregs (CD4(+)Foxp3(+)Helios(-)) was generated in correlation with the matrix
      metalloproteinase (MMP) cascade and transforming growth factor-beta (TGF-beta)
      activation that were manifested mainly by hepatic stellate cells. Moreover, the
      induction of induced Tregs and wound healing were both impaired in mice lacking
      TGF-beta signaling or MMPs. The depletion of induced Tregs also impeded wound
      healing for tissue repair. Together, this study demonstrates the mechanism that
      the loss of nTregs through apoptosis in the acute phase may facilitate
      inflammation, while regenerated Tregs through MMP9/13-dependent activation of TGF
      beta in the healing phase are critical to terminate inflammation and allow for
      wound healing. 

PMID- 24280649
TI  - Visual eyes: a quantitative analysis of the photoreceptor layer in deep-sea
      sharks.
AB  - The marine environment presents unique visual challenges for a range of
      organisms, particularly those dwelling at great depths, where sunlight may either
      be absent or drop to very low levels. Under these environmental conditions, the
      visual system must maximise light absorption in order to enhance the detection of
      prey, predators and potential mates. Using stereological analysis of retinal
      wholemounts, the distribution and number of photoreceptors (rods) was determined
      for 5 deep-sea shark species from a range of depths (46-1,500 m). All species
      possessed areas of increased photoreceptor density (with peaks between 41,000 and
      82,000 rods/mm(2)) within discrete regions of the retina. The total number of
      rods in the photoreceptor layer also varied between 17 * 10(6) and 63 * 10(6). It
      is evident that increasing sensitivity of the retina is an important adaptation
      to life in the deep sea. The location of discrete areas of high cell density
      within the photoreceptor layer of the retina corresponds to discrete areas of the
      visual field that are sampled at a higher intensity, hence increasing
      sensitivity. The location of these areas of increased sensitivity differed
      between the species of this study. The disparity of areas of increased
      sensitivity seen between species is thought to reflect distinctive predator
      avoidance and prey capture strategies. This study reveals that the visual demands
      of deep-sea sharks vary interspecifically and that sampling of each species'
      visual field is not solely determined by its habitat.

PMID- 24280650
TI  - What is a memory schema? A historical perspective on current neuroscience
      literature.
AB  - The term "schema" has been used to describe vastly different knowledge structures
      within the memory neuroscience literature. Ambiguous terminology hinders cross
      study comparisons and confounds interpretation of the suggested role of the
      ventromedial prefrontal cortex (vmPFC) in schema functions. Based on an extensive
      review of the psychological literature, we propose a framework for distinguishing
      memory schemas from other knowledge structures. The framework includes a
      definition of schema as possessing four necessary and sufficient features, and
      four additional features schemas are sensitive to, which are not required but do
      play a frequent and central role in schema functions. Necessary schema features
      are (1) an associative network structure, (2) basis on multiple episodes, (3)
      lack of unit detail, and (4) adaptability. Features schemas are sensitive to are
      (5) chronological relationships, (6) hierarchical organization, (7) cross
      connectivity, and (8) embedded response options. Additionally, we suggest that
      vmPFC activity observed in studies of schemas corresponds with participants'
      coordination of existing schemas with ongoing task demands. 

PMID- 24280651
TI  - Surgical navigation in urology: European perspective.
AB  - PURPOSE OF REVIEW: Use of virtual reality to navigate open and endoscopic surgery
      has significantly evolved during the last decade. Current status of seven most
      interesting projects inside the European Association of Urology section of uro
      technology is summarized with review of literature. RECENT FINDINGS: Marker-based
      endoscopic tracking during laparoscopic radical prostatectomy using high
      definition technology reduces positive margins. Marker-based endoscopic tracking
      during laparoscopic partial nephrectomy by mechanical overlay of three
      dimensional-segmented virtual anatomy is helpful during planning of trocar
      placement and dissection of renal hilum. Marker-based, iPAD-assisted puncture of
      renal collecting system shows more benefit for trainees with reduction of
      radiation exposure. Three-dimensional laser-assisted puncture of renal collecting
      system using Uro-Dyna-CT realized in an ex-vivo model enables minimal radiation
      time. Electromagnetic tracking for puncture of renal collecting system using a
      sensor at the tip of ureteral catheter worked in an in-vivo model of porcine
      ureter and kidney. Attitude tracking for ultrasound-guided puncture of renal
      tumours by accelerometer reduces the puncture error from 4.7 to 1.8 mm.
      Feasibility of electromagnetic and optical tracking with the da Vinci
      telemanipulator was shown in vitro as well as using in-vivo model of
      oesophagectomy. Target registration error was 11.2 mm because of soft-tissue
      deformation. SUMMARY: Intraoperative navigation is helpful during percutaneous
      puncture collecting system and biopsy of renal tumour using various tracking
      techniques. Early clinical studies demonstrate advantages of marker-based
      navigation during laparoscopic radical prostatectomy and partial nephrectomy.
      Combination of different tracking techniques may further improve this interesting
      addition to video-assisted surgery.

PMID- 24280652
TI  - Lower urinary tract symptom: still too much focus on the prostate?
AB  - PURPOSE OF REVIEW: Male patients with lower urinary tract symptoms have
      historically been managed in a prostate centric fashion. Population studies
      highlighting the prevalence and significance of storage symptoms, including
      nocturia, have meant a shift in the way men with lower urinary tract symptoms are
      assessed and managed. We review the recent guidelines and publications that have
      addressed this change in approach. RECENT FINDINGS: A new beta-3 adrenoreceptor
      agonist has demonstrated significant improvement in storage symptoms and appears
      to be well tolerated. SUMMARY: We support a continued move towards a patient
      focused and management using the current guidelines.

PMID- 24280653
TI  - Trajectories of suicidal ideation and posttraumatic stress symptoms among former
      prisoners of war: a 17-year longitudinal study.
AB  - War captivity is one of the most severe human-inflicted traumatic experiences
      with wide and substantial long-term negative effects. However, only one
      retrospective study examined suicidal ideation (SI) among ex-prisoners of war (ex
      POWs). This study aimed to prospectively assess SI among ex-POWs and its
      associations with posttraumatic stress disorder (PTSD) symptoms over a 17-year
      period. Two groups of male Israeli veterans from the 1973 Yom Kippur War were
      examined: ex-POWs and comparable veterans who were not taken captive. Both groups
      were assessed via self-report measures of SI and PTSD symptoms at three time
      points: T1 18 (1991), T2 30 (2003), and T3 35 (2008) years after the war. Latent
      growth curve modeling (LGM) results showed that ex-POWs reported higher levels of
      SI at T2 and T3 and a pattern of increase in SI levels trajectory over time,
      compared to control veterans. Furthermore, among ex-POWs, PTSD symptoms at T1
      contributed to the increase in rate of change in SI overtime. In addition, PTSD
      symptoms affected SI at the same measurement, above and beyond above the
      trajectories of SI. Clinical implications of these findings for the relations
      between captivity trauma and suicidality are discussed. 

PMID- 24280654
TI  - Nystagmus following acute avermectins poisoning.
AB  - BACKGROUND: Acute pesticide poisoning is a major public health problem in the
      world. Most pesticides are toxic to human beings, because of diverse components
      resulting in different reaction. OBJECTIVE: As clinicians identify various
      symptoms due to pesticide poisoning, it is necessary for the diagnosis and
      treatment for treating such toxins. Accidents associated with acute avermectins
      poisoning are rarely reported, especially self-induced nystagmus. In the present
      study, a case of human abamectin poisoning with relevant toxic effects has been
      reported. CONCLUSIONS: Acute avermectins poisoning-induced nystagmus may be
      affected due to the vestibular cerebellar system, but the exact mechanism and
      pharmacological basis is still worthy of further study.

PMID- 24280655
TI  - Therapeutic and protective effects of Caesalpinia gilliesii and Cajanus cajan
      proteins against acetaminophen overdose-induced renal damage.
AB  - The present work aims to evaluate the protective and ameliorative effects of two
      plant-derived proteins obtained from the seeds of Cajanus cajan and Caesalpinia
      gilliesii(Leguminosae) against the toxic effects of acetaminophen in kidney after
      chronic dose through determination of certain biochemical markers including total
      urea, creatinine, and kidney marker enzyme, that is, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH). In addition histopathological examination of intoxicated
      and treated kidney with both proteins was performed. The present results show a
      significant increase in serum total urea and creatinine, while significant
      decrease in GAPDH. Improvement in all biochemical parameters studied was
      demonstrated, which was documented by the amelioration signs in rats kidney
      architecture. Thus, both plant protein extracts can counteract the nephrotoxic
      process, minimize damage to the kidney, delay disease progression, and reduce its
      complications.

PMID- 24280656
TI  - Vaccines within vaccines: the use of adenovirus types 4 and 7 as influenza
      vaccine vectors.
AB  - Adenovirus Types 4 and 7 (Ad4 and Ad7) are associated with acute respiratory
      distress (ARD). In order to prevent widespread Ad-associated ARD (Ad-ARD) the
      United States military immunizes new recruits using a safe and effective
      lyophilized wildtype Ad4 and Ad7 delivered orally in an enteric-coated capsule.
      We cloned Ad4 and Ad7 and modified them to express either a GFP-Luciferase
      (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (HA1-con).
      BALB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.)
      and intranasally (i.n.). Ad4 induced significantly higher luciferase expression
      levels as compared with Ad7 by both routes. Ad7 transduction was restored using a
      human CD46+ transgenic mouse model. Mice immunized with serial dilutions of
      viruses expressing the HA1-con influenza vaccine gene were challenged with 100
      MLD 50 of influenza virus. Ad4 protected BALB/c mice at a lower dose by i.m.
      immunization as compared with Ad7. Unexpectedly, there was no difference in
      protection by i.n. immunization. Although Ad7 i.m. transduction was restored in
      CD46+ transgenic mice, protection against influenza challenge required even
      higher doses as compared with the BALB/c mice. However, Ad7 i.n. immunized CD46+
      transgenic mice were better protected as compared with Ad4. Interestingly, the
      restoration of Ad7 transduction in CD46+ mice did not increase vaccine efficacy
      and indicates that Ad7 may transduce a different subset of cells through
      alternative receptors in the absence of CD46. These data indicate that both Ad4
      and Ad7 can effectively induce anti-H1N1 immunity against a heterologous
      challenge using a centralized H1 gene. Future studies in non-human primates or
      human clinical trials will determine the overall effectiveness of Ad4 and Ad7 as
      vaccines for influenza. 

PMID- 24280658
TI  - Application of bone marrow and adipose-derived mesenchymal stem cells for testing
      the biocompatibility of metal-based biomaterials functionalized with ascorbic
      acid.
AB  - In this study, metal-based biomaterials were functionalized with ascorbic acid
      (LAA). Two types of substrates were used: austenitic steel 316L and titanium
      Ti6Al4V. Coatings were prepared with the sol-gel method and applied on metal
      surfaces using the dip-coating technique. Ascorbic acid was delivered with SiO2
      coating at concentrations of 0.1 and 0.4 M. The morphology of the surfaces and
      coatings was determined using scanning electron microscope (SEM), whereas their
      elemental composition by SEM-EDX. Immobilization of ascorbic acid in the coatings
      was confirmed with Raman spectroscopy. The biocompatibility of the materials
      obtained was tested in vitro using both bone marrow- and adipose-derived
      mesenchymal stem cells (BMMSC and ADMSC, respectively). Proliferation rate and
      morphology of cells cultured in the presence of designed biomaterials were
      monitored after 24, 48, 120 and 168 h of propagation. The results obtained
      indicated that silica coatings doped with 0.4 M LAA had a positive effect on the
      proliferation rate of investigated cells, and in some cases on the growth pattern
      of culture. 

PMID- 24280657
TI  - Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal
      chlorpyrifos exposure on serotonergic pathways.
AB  - This study explores how glucocorticoids sensitize the developing brain to the
      organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard
      therapeutic dose (0.2mg/kg) of dexamethasone on gestational days 17-19; pups were
      given subtoxic doses of chlorpyrifos on postnatal days 1-4 (1mg/kg, <10%
      cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from
      postnatal day 30 to day 150, assessing the expression of 5HT receptors and the
      5HT transporter, along with 5HT turnover (index of presynaptic impulse activity)
      in brain regions encompassing all the 5HT projections and cell bodies. These
      parameters are known targets for neurodevelopmental effects of dexamethasone and
      chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in
      the expression of 5HT synaptic proteins, with a progressive increase from
      adolescence to adulthood; this effect was attenuated by prenatal dexamethasone
      treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT
      turnover, indicating that the receptor upregulation was an adaptive response to
      deficient presynaptic activity. Turnover deficiencies were magnified by
      dexamethasone pretreatment, worsening the functional impairment caused by
      chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected
      relative sparing of adverse effects compared to males. Nevertheless, prenatal
      dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor
      expression in females, demonstrating the same adverse interaction.
      Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in
      maternal stress; accordingly, our results indicate that this group represents a
      large subpopulation that may have heightened vulnerability to developmental
      neurotoxicants such as the organophosphates. 

PMID- 24280659
TI  - Allergic contact dermatitis from buprenorphine and oral tolerance to other opioid
      derivatives in three patients.
AB  - Transdermal buprenorphine (TDB) is a widely used analgesic for moderate pain. TDB
      is generally well tolerated, but both irritant and allergic contact dermatitis
      occur at patch application sites. Oral opioid tolerance in patients with allergic
      contact dermatitis to TDB remains controversial. Here, we describe 3 patients
      with allergic contact dermatitis to TDB who subsequently used oral opioid
      derivatives without adverse reactions. Thus, oral intolerance to opioid
      derivatives is not a rule in patients with allergic contact dermatitis to TDB,
      but the possibility should be taken into consideration.

PMID- 24280660
TI  - Development and validation of a web-based survey on the use of personal
      communication devices by hospital registered nurses: pilot study.
AB  - BACKGROUND: The use of personal communication devices (such as basic cell phones,
      enhanced cell phones or smartphones, and tablet computers) in hospital units has
      risen dramatically in recent years. The use of these devices for personal and
      professional activities can be beneficial, but also has the potential to
      negatively affect patient care, as clinicians may become distracted by these
      devices. OBJECTIVE: No validated questionnaire examining the impact of the use of
      these devices on patient care exists; thus, we aim to develop and validate an
      online questionnaire for surveying the views of registered nurses with experience
      of working in hospitals regarding the impact of the use of personal communication
      devices on hospital units. METHODS: A 50-item, four-domain questionnaire on the
      views of registered nursing staff regarding the impact of personal communication
      devices on hospital units was developed based on a literature review and
      interviews with such nurses. A repeated measures pilot study was conducted to
      examine the psychometrics of a survey questionnaire and the feasibility of
      conducting a larger study. Psychometric testing of the questionnaire included
      examining internal consistency reliability and test-retest reliability in a
      sample of 50 registered nurses. RESULTS: The response rate for the repeated
      measures was 30%. Cronbach coefficient alpha was used to examine the internal
      consistency and reliability, and in three of the four question groups
      (utilization, impact, and opinions), the correlation was observed to be very
      high. This suggests that the questions were measuring a single underlying theme.
      The Cronbach alpha value for the questions in the performance group, describing
      the use of personal communication devices while working, was lower than those for
      the other question groups. These values may be an indication that the assumptions
      underlying the Cronbach alpha calculation may have been violated for this group
      of questions. A Spearman rho correlation was used to determine the test-retest
      reliability. There was a strong test-retest reliability between the two tests for
      the majority of the questions. The average test-retest percent of agreement for
      the Likert scale responses was 74% (range 43-100%). Accounting for responses
      within the 1 SD range on the Likert scale increased the agreement to 96% (range
      87-100%). Missing data were in the range of 0 to 7%. CONCLUSIONS: The
      psychometrics of the questionnaire showed good to fair levels of internal
      consistency and test-retest reliability. The pilot study demonstrated that our
      questionnaire may be useful in exploring registered nurses' perceptions of the
      impact of personal electronic devices on hospital units in a larger study.

PMID- 24280661
TI  - Prediction of the remnant liver hypertrophy ratio after preoperative portal vein
      embolization.
AB  - BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of
      major hepatectomy. Various conditions might affect remnant liver hypertrophy
      after PVE. The aim of the present study was to clarify the factors that affect
      remnant liver hypertrophy and to establish a prediction formula for the
      hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE
      for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients),
      hepatocellular carcinoma (8 patients), and other diseases (2 patients) were
      enrolled in this study. For the prediction of the hypertrophy ratio, a formula
      with stepwise multiple regression analysis was set up. The following parameters
      were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma
      disappearance rate of indocyanine green (ICGK), platelet count, prothrombin
      activity, serum albumin, serum total bilirubin at the time of PVE and the maximum
      value before PVE (Max Bil), as well as a history of cholangitis, diabetes
      mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5
      parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001),
      ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007).
      The following prediction formula was established: 101.6 - 0.78 * age - 0.88 *
      FLR% + 128 * ICGK - 1.48 * Max Bil (mg/dl) - 21.2 * chemotherapy. The value
      obtained using this formula significantly correlated with the actual value (r =
      0.72, p < 0.001). A 10-fold cross validation also showed significant correlation
      (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a
      sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m
      diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy
      showed a significantly smaller increase in the uptake ratio of the remnant liver
      in patients with prediction values <20% than in those with values >=20% (6.8 vs.
      20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the
      hypertrophy ratio after PVE, which may provide a new therapeutic strategy for
      major hepatectomy.

PMID- 24280663
TI  - Photo Quiz. A 59-year-old woman with chronic skin lesions of the leg.

PMID- 24280662
TI  - Developing a new, national approach to surveillance for ventilator-associated
      events: executive summary.

PMID- 24280666
TI  - Effects of host plant and larval density on intraspecific competition in larvae
      of the emerald ash borer (Coleoptera: Buprestidae).
AB  - Competition for food, mates, and space among different individuals of the same
      insect species can affect density-dependent regulation of insect abundance or
      population dynamics. The emerald ash borer, Agrilus planipennis Fairmaire
      (Coleoptera: Buprestidae), is a serious invasive pest of North American ash
      (Fraxinus spp.) trees, with its larvae feeding in serpentine galleries between
      the interface of sapwood and phloem tissues of ash trees. Using artificial
      infestation of freshly cut logs of green ash (Fraxinus pennsylvanica Marshall)
      and tropical ash (Fraxinus uhdei [Wenzig] Lingelsh) with a series of egg
      densities, we evaluated the mechanism and outcome of intraspecific competition in
      larvae of A. planipennis in relation to larval density and host plant species.
      Results from our study showed that as the egg densities on each log (1.5-6.5 cm
      in diameter and 22-25 cm in length) increased from 200 to 1,600 eggs per square
      meter of surface area, larval survivorship declined from ?68 to 10% for the green
      ash logs, and 86 to 55% for tropical ash logs. Accordingly, larval mortality
      resulting from cannibalism, starvation, or both, significantly increased as egg
      density increased, and the biomass of surviving larvae significantly decreased on
      both ash species. When larval density was adjusted to the same level, however,
      larval mortality from intraspecific competition was significantly higher and mean
      biomasses of surviving larvae was significantly lower in green ash than in
      tropical ash. The role of intraspecific competition of A. planipennis larvae in
      density-dependent regulation of its natural population dynamics is discussed. 

PMID- 24280667
TI  - Association of dark-adapted visual function with retinal structural changes in
      patients with Stargardt disease.
AB  - PURPOSE: To evaluate dark-adapted retinal sensitivity in patients with Stargardt
      disease (STGD1) using a modified MP-1 microperimeter and to compare the
      sensitivity loss with structural changes observed using spectral domain optical
      coherence tomography and confocal scanning laser ophthalmoscope infrared imaging.
      METHODS: Twelve STGD1 patients and 10 normally sighted controls participated.
      Dark-adapted mean sensitivity (MS) was obtained using a MP-1 microperimeter.
      Additionally, MS percent difference between the patients and the controls was
      obtained. Sensitivity results were superimposed on confocal scanning laser
      ophthalmoscope infrared images and compared with corresponding spectral domain
      optical coherence tomography scans. RESULTS: Dark-adapted MS +/- standard
      deviation was 8.34 +/- 1.54 dB for the controls and 3.68 +/- 1.74 dB for STGD1
      patients (P < 0.001). There was a significant reduction in MS of 24.0% in these
      patients. Sensitivity reductions were observed in areas that showed changes on
      confocal scanning laser ophthalmoscope infrared images and on spectral domain
      optical coherence tomography, including disorganizational loss of the retinal
      pigment epithelium, and abnormal photoreceptor inner segment ellipsoid and
      external limiting membrane reflectance bands. CONCLUSION: With topographical
      accuracy, dark-adapted MS measurements can be made in STGD1 patients and controls
      using the MP-1 microperimeter. Sensitivity loss is associated with structural
      changes. This finding can be useful for the determination of optimal areas for
      potential improvement of retinal function in patients with Stargardt disease.

PMID- 24280668
TI  - Choroidal thickness in diabetic retinopathy: the influence of antiangiogenic
      therapy.
AB  - PURPOSE: To analyze the effect of anti-vascular endothelial growth factor agents
      (anti-VEGF) in submacular choroidal thickness (CT) of diabetic retinopathy (DR)
      patients. METHODS: Cross-sectional study, which included 25 DR patients (50 eyes)
      divided in 2 groups, according to DR stage and previous treatments:
      nonproliferative DR and diffuse diabetic macular edema in both eyes, submitted to
      macular laser in both eyes and anti-VEGF injection only in 1 eye
      (nonproliferative diabetic retinopathy + diabetic macular edema group, n = 11);
      and proliferative DR in both eyes, treated with panretinal photocoagulation in
      both eyes and anti-VEGF injection only in 1 eye (proliferative diabetic
      retinopathy group, n = 14). In the study visit, all patients underwent optical
      coherence tomography with enhanced depth imaging protocol. Choroidal segmentation
      was performed manually. The medium CT in central macular area (CCT) and the CT in
      centrofoveal B-scan were obtained automatically. RESULTS: The 25 eyes treated
      with anti-VEGF showed a reduction on CCT (P = 0.002) and subfoveal CT (P =
      0.004), compared with the fellow eyes treated with laser only. Independent
      evaluation of PDR group revealed similar results (CCT, P = 0.02; subfoveal CT, P
      = 0.03). In nonproliferative diabetic retinopathy + diabetic macular edema group,
      CCT was also significantly thinner in eyes treated with anti-VEGF (P = 0.04). A
      correlation between the number of injections and a thinner CT was found in this
      group (P = 0.03) and in the evaluation of all eyes together (P = 0.03).
      CONCLUSION: Diabetic eyes treated with anti-VEGF agents have reduced CT.

PMID- 24280669
TI  - Vitreomacular interface and outer foveal microstructure in fellow eyes of
      patients with unilateral macular holes.
AB  - PURPOSE: To investigate the relationship between the vitreomacular interface and
      the integrity of the photoreceptor microstructures in the normal fellow eyes of
      patients with unilateral macular holes. METHODS: Retrospective observational case
      series. Fifty-five normal fellow eyes of 55 patients with unilateral macular
      holes were enrolled in the study. All patients underwent complete ophthalmologic
      examination including best-corrected visual acuity, slit-lamp biomicroscopy,
      fundus photography, and spectral domain optical coherence tomography at initial
      and follow-up visits. The features of the vitreomacular interface were graded
      based on spectral domain optical coherence tomography findings. RESULTS: At the
      initial visit, 28 of 55 eyes (51%) had vitreomacular attachments with or without
      perifoveal posterior vitreous detachment. On their initial visit, a triangular
      elevation of the cone outer segment tips line was identified in 11 of 18 eyes
      (61%) with perifoveal posterior vitreous detachment across all quadrants with
      persistent attachment to the fovea. Conversely, none of the remaining 37 eyes
      with the other stages of posterior vitreous detachment showed any abnormalities.
      Over a mean follow-up period of 18 months (range, 12-24 months), the elevation of
      the cone outer segment tips line resolved after spontaneous vitreomacular
      separation without macular holes in 3 eyes, remained unchanged in 6 eyes, and
      showed progression to a full-thickness macular hole in 2 eyes. CONCLUSION: These
      findings suggest that an elevation of the cone outer segment tips line in the
      normal fellow eyes of patients with macular holes is caused by the focal traction
      of the vitreous at the foveal center. This is considered to be an important
      primary change observed in the macular tissue in full-thickness macular hole
      formation.

PMID- 24280670
TI  - Allergen immunotherapy and tolerance.
AB  - Successful allergen-specific immunotherapy (AIT) is associated with a marked
      decrease in symptoms on allergen exposure, a reduced requirement for 'rescue'
      anti-allergic drugs and improvement in patients' quality of life. These benefits
      persist for at least several years following discontinuation of immunotherapy -
      the hallmark of clinical and immunological tolerance. AIT has been shown to
      modulate both innate and adaptive immunological responses. Early suppression of
      innate effector cells of allergic inflammation (mast cells, basophils),
      regulation of pro-allergic T helper 2 type (Th 2) responses and IgE+ B cell
      responses have been shown to occur both in the tissue and in the peripheral blood
      during AIT. The allergen-tolerant state is associated with local and systemic
      induction of distinct populations of allergen-specific T regulatory cells
      including IL-10+ Tregs (Tr1 cells), TGF-beta+ Tregs and FoxP3+ memory T regs. B
      cells are switched in favour of producing IgG (particularly IgG4) antibodies and
      associated blocking activity for IgE-dependent events, including basophil
      activation and IgE-facilitated allergen binding to B cells. An induction of IL
      10+ B regulatory cells and alterations in dendritic cell subsets have also
      recently been described. These events are followed by the induction of T
      regulatory cells, suppression of allergen-specific T cell proliferation and
      immune deviation from Th2 in favour of Th1 responses. Alternative mechanisms of
      tolerance include apoptosis/deletion of antigen-specific memory Th2 cells and/or
      a failure of co-stimulation leading to T cell anergy.

PMID- 24280671
TI  - Sublingual immunotherapy: recent advances.
AB  - The practice of administering sublingual immunotherapy for respiratory allergy is
      gaining more and more diffusion worldwide as a consequence of the robust
      demonstration of clinical efficacy and safety provided by recent high-powered and
      well-designed studies, confirming for individual seasonal allergens the results
      of previous metanalyses in adult and pediatric populations. Preliminary evidence
      derives from recent rigorous trials on perennial allergens, like house dust
      mites, and specifically designed studies addressed the benefits on asthma.
      Emerging research suggests that SLIT may have a future role in other allergic
      conditions such as atopic dermatitis, food, latex and venom allergy. Efforts to
      develop a safer and more effective SLIT for inhalant allergens have led to the
      development of allergoids, recombinant allergens and formulations with adjuvants
      and substances targeting antigens to dendritic cells that possess a crucial role
      in initiating immune responses. The high degree of variation in the evaluation of
      clinical effects and immunological changes requires further studies to identify
      the candidate patients to SLIT and biomarkers of short and long term efficacy.
      Appropriate management strategies are urgently needed to overcome the barriers to
      SLIT compliance.

PMID- 24280672
TI  - Ventricular strain in fetuses with aortic stenosis and evolving hypoplastic left
      heart syndrome before and after prenatal aortic valvuloplasty.
AB  - OBJECTIVE: The impact of prenatal intervention on fetal cardiac function has not
      been well defined. We assessed standard ventricular function parameters and
      strain in fetuses with evolving hypoplastic left heart syndrome (HLHS) treated
      with fetal aortic valvuloplasty (fAVP). METHODS: Fetuses with valvar aortic
      stenosis that underwent fAVP were studied. Echocardiographic images prior to
      intervention (Pre), within 1 week after fAVP (Post), and at the last prenatal
      follow-up examination (FU) were analyzed. Left ventricular (LV) circumferential
      (LVCS) and longitudinal strain (LVLS), right ventricular (RV) longitudinal strain
      (RVLS), and LV end-diastolic dimension Z-scores (LVIDD-Z) were documented and
      compared according to postnatal outcome. RESULTS: Among 57 fetuses studied, the
      postnatal outcome was biventricular in 23 and univentricular in 34. Prior to
      fAVP, strain was <4 in most cases, regardless of outcome. Biventricular fetuses
      had higher LVCS and LVLS segmental strain than univentricular fetuses. Among
      fetuses with a biventricular outcome, LVCS and LVLS increased as LVIDD-Z
      decreased in late gestation, whereas LVCS and LVLS remained <4 in univentricular
      fetuses, although the LVIDD-Z decreased to <0 in all cases. Septal RVLS increased
      after fAVP in the biventricular but not the univentricular outcome group.
      CONCLUSION: In utero aortic valve dilation appears to have a beneficial effect on
      both LV and RV function in some fetuses with evolving HLHS.

PMID- 24280673
TI  - Season of birth in suicides: excess of births during the summer among
      schizophrenic suicide victims.
AB  - BACKGROUND: Season of birth is associated with several psychiatric disorders and
      suicidal behavior. We explored the association between the season of birth and
      suicide among schizophrenic and psychotic suicide victims. METHODS: The study
      sample consisted of all suicides in the province of Oulu in Northern Finland from
      1989 to 2010. Causes of death were extracted from death certificates, and
      psychiatric diagnoses associated with the hospital treatments were obtained from
      the Finnish Hospital Discharge Register. The seasons were defined as follows:
      winter (from November to January), spring (from February to April), summer (from
      May to July), and autumn (from August to October). Suicide victims (n = 1,902)
      were categorized as having either schizophrenia (n = 228) or psychosis other than
      schizophrenia (n = 240). Suicide victims without any hospital-treated mental
      disorder (n = 1,434) were used as a comparison group. RESULTS: The distribution
      of births among suicide victims with schizophrenia differed statistically
      significantly from that observed in the general population, with a peak in summer
      (OR 1.2, 95% CI 1.0-1.5). CONCLUSIONS: Birth during summer may predispose
      schizophrenic persons to suicide. The putative roles of serotonin, dopamine, and
      vitamin D status in the season of birth of psychotic suicide victims are
      discussed.

PMID- 24280674
TI  - Environmental assessment of biofuel pathways in Ile de France based on ecosystem
      modeling.
AB  - The objective of the work reported here was to reduce the uncertainty on the
      greenhouse gas balances of biofuels using agro-ecosystem modeling at a high
      resolution over the Ile-de-France region in Northern France. The emissions
      simulated during the feedstock production stage were input to a life-cycle
      assessment of candidate biofuel pathways: bioethanol from wheat, sugar-beet and
      miscanthus, and biodiesel from oilseed rape. Compared to the widely-used
      methodology based on fixed emission factors, ecosystem modeling lead to 55-70%
      lower estimates for N2O emissions, emphasizing the importance of regional
      factors. The life-cycle GHG emissions of first-generation biofuels were 50-70%
      lower than fossil-based equivalents, and 85% lower for cellulosic ethanol. When
      including indirect land-use change effects, GHG savings became marginal for
      biodiesel and wheat ethanol, but were positive due to direct effects for
      cellulosic ethanol. 

PMID- 24280675
TI  - Heat shock protein 90 and role of its chemical inhibitors in treatment of
      hematologic malignancies.
AB  - Heat shock protein 90 (Hsp90) is a conserved and constitutively expressed
      molecular chaperone and it has been shown to stabilize oncoproteins and
      facilitate cancer development. Hsp90 has been considered as a therapeutic target
      for cancers and three classes of Hsp90 inhibitors have been developed: (1)
      benzoquinone ansamycin and its derivatives, (2) radicicol and its derivates, and
      (3) small synthetic inhibitors. The roles of these inhibitors in cancer treatment
      have been studied in laboratories and clinical trials, and some encouraging
      results have been obtained. Interestingly, targeting of Hsp90 has been shown to
      be effective in inhibition of cancer stem cells responsible for leukemia
      initiation and progression, providing a strategy for finding a cure. Because
      cancer stem cells are well defined in some human leukemias, we will focus on
      hematologic malignancies in this review. 

PMID- 24280676
TI  - Involvement of Multiple Transporters-mediated Transports in Mizoribine and
      Methotrexate Pharmacokinetics.
AB  - Mizoribine is administered orally and excreted into urine without being
      metabolized. Many research groups have reported a linear relationship between the
      dose and peak serum concentration, between the dose and AUC, and between AUC and
      cumulative urinary excretion of mizoribine. In contrast, a significant
      interindividual variability, with a small intraindividual variability, in oral
      bioavailability of mizoribine is also reported. The interindividual variability
      is mostly considered to be due to the polymophisms of transporter genes.
      Methotrexate (MTX) is administered orally and/or by parenteral routes, depending
      on the dose. Metabolic enzymes and multiple transporters are involved in the
      pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked
      interindividual variability and saturation with increase in the dose of MTX, with
      a small intraindividual variability, where the contribution of gene polymophisms
      of transporters and enzymes is suggested. Therapeutic drug monitoring of both
      mizoribine and MTX is expected to improve their clinical efficacy in the
      treatment of rheumatoid arthritis. 

PMID- 24280677
TI  - Role of transient receptor potential vanilloid 1 in inflammation and autoimmune
      diseases.
AB  - Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel,
      is a receptor activated by high temperatures and chemical agonists such as the
      vanilloids and protons. Because of these properties, TRPV1 has emerged as a
      polymodal nocisensor of nociceptive afferent neurons. TRPV1 is thought to be a
      central transducer of hyperalgesia and a prime target for controlling pain
      pharmacologically because it is a point where many proalgesic pathways converge
      and it is upregulated and sensitized by inflammation and injury. However, whether
      TRPV1 agonists promote or inhibit inflammation remains unclear. We recently
      demonstrated that SA13353 (1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4
      pyridyl)propyl]urea), a novel TRPV1 agonist, inhibits tumor necrosis factor-a
      production by the activation of capsaicin-sensitive afferent neurons and reduces
      the severity of symptoms in kidney injury, lung inflammation, arthritis, and
      encephalomyelitis. These results suggest that TRPV1 agonists may act as anti
      inflammatories in certain inflammatory and autoimmune conditions in vivo. Given
      the potential deleterious effects of inhibiting the population of channels with a
      protective function, caution should be taken in the use of potent TRPV1
      antagonists as a general strategy to treat inflammation. Further studies are
      required to clarify the role of TRPV1 and neuropeptides, which are released
      because of TRPV1 activation in inflammation and autoimmune diseases. 

PMID- 24280678
TI  - Phytomedicine in otorhinolaryngology and pulmonology: clinical trials with herbal
      remedies.
AB  - Phytomedicine has become an important alternative treatment option for patients
      in the Western world, as they seek to be treated in a holistic and natural way
      after an unsatisfactory response to conventional drugs. Ever since herbal
      remedies have been introduced in the Western world, clinicians have raised
      concerns over their efficacy and possible side-effects. A PubMed (Medline) search
      was performed covering the last five years (01/07-04/12) and including 55
      prospective clinical randomized control trials in the medical specialities
      Otorhinolaryngology and Pulmonology. In this review, we present evidence-based
      clinical data with herbal remedies and try to enlighten the question of efficacy
      and reliability of phytomedicine. 

PMID- 24280679
TI  - A Perspective on the Comparative Antileukemic Activity of 5-Aza-2'-deoxycytidine
      (Decitabine) and 5-Azacytidine (Vidaza).
AB  - 5-Aza-2'-deoxycytidine (5-AZA-CdR, decitabine, Dacogen(r)) and 5-azacytidine (5
      AC, Vidaza(r)) are epigenetic agents that have been approved for the clinical
      treatment of the hematological malignancy myelodysplastic syndrome (MDS) and are
      currently under clinical evaluation for the treatment of acute myeloid leukemia
      (AML). Most investigators currently classify 5-AZA-CdR and 5-AC as inhibitors of
      DNA methylation, which can reactivate tumor suppressor genes silenced by this
      epigenetic event. Examination of the pharmacology of these analogues reveals
      important differences with respect to their molecular mechanism of action. The
      action of 5-AZA-CdR is due to its incorporation into DNA. 5-AC is a riboside
      analogue that is incorporated primarily into RNA. A small fraction of 5-AC is
      converted to its deoxyribose form by ribonucleotide reductase and subsequently
      incorporated into DNA. The incorporation of 5-AC into RNA can interfere with the
      biological function of RNA and result in an inhibition protein synthesis.
      Microarray analysis revealed that both these analogues target the expression of
      different cohorts of genes. Preclinical studies show that 5-AZA-CdR is a more
      effective antileukemic agent than 5-AC. One explanation for this observation is
      that 5-AC blocks the progression of some leukemic cells from G1 into S phase, and
      this protects these cells from the chemotherapeutic action of this riboside
      analogue related to its incorporation into DNA. However, differences in
      chemotherapeutic efficacy of these related analogues have not been clearly
      demonstrated in clinical trials in patients with hematological malignancies.
      These observations should be taken into consideration in the design of new
      clinical trials using 5-AZA-CdR or 5-AC in patients with MDS and AML. 

PMID- 24280680
TI  - The Chemical Components of Sesbania grandiflora Root and Their Antituberculosis
      Activity.
AB  - Three isoflavanoids, isovestitol (1), medicarpin (2), and sativan (3), along with
      another known compound, betulinic acid (4), were isolated from the root of
      Sesbania grandiflora. The structures of the isolated compounds were characterised
      by means of spectroscopic techniques (UV, IR, MS, 1H- and 13C-NMR, DEPT, COSY,
      HMQC, HMBC, and MS analysis). All the tested compounds 1-4 exhibited
      antituberculosis activity against Mycobacterium tuberculosis H37Rv, with MIC
      values of 50 ug/mL for compounds 1-3, and 100 ug/mL for compound 4, whereas, the
      methanol extract exhibited antituberculosis activity of 625 ug/mL. This is the
      first report on the occurrence of isoflavonoids in this plant and their
      antituberculosis activity. 

PMID- 24280681
TI  - miR-204 inhibits epithelial to mesenchymal transition by targeting slug in
      intrahepatic cholangiocarcinoma cells.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) play critical roles during carcinogenesis and
      cancer progression. Down-regulation of miR-204 has been frequently observed in
      various cancers. In this study, we investigated the roles and mechanisms of miR
      204 in human intrahepatic cholangiocarcinoma (ICC). METHODS: The relative
      expression of miR-204 in ICC tissues and cell lines was monitored by qRT-PCR.
      Effects of miR-204 were studied in human ICC cell lines HuH28 and HuCCT1, and
      cells were analyzed for proliferation, migration and invasion. Expression levels
      of miR-204 target gene Slug and EMT markers (E-cadherin and vimentin) in ICC cell
      lines and tissues were measured by qRT-PCR, western blotting and
      immunofluorescence. RESULTS: miR-204 was frequently downregulated in human ICC,
      and the low-level expression of miR-204 was significantly associated with lymph
      node metastasis. Overexpression of miR-204 dramatically suppressed ICC cell
      migration and invasion, as well as the epithelial-mesenchymal transition process
      (EMT). Slug was identified as a direct target of miR-204, and its downregulation
      by miR-204 in HuH28 cells reversed EMT, as shown by the increased expression of
      the epithelial marker E-cadherin and decreased expression of the mesenchymal
      marker vimentin. CONCLUSION: These findings suggest that miR-204 plays negative
      roles in the invasive and/or metastatic potential of ICC, and that its
      suppressive effects are mediated by repressing Slug expression.

PMID- 24280682
TI  - Retinoblastoma and ambient exposure to air toxics in the perinatal period.
AB  - We examined ambient exposure to specific air toxics in the perinatal period in
      relation to retinoblastoma development. Cases were ascertained from California
      Cancer Registry records of children diagnosed between 1990 and 2007 and matched
      to California birth certificates. Controls were randomly selected from state
      birth records for the same time period. We chose 27 air toxics for the present
      study that had been listed as possible, probable, or established human
      carcinogens by the International Agency for Research on Cancer. Children (103
      cases and 30,601 controls) included in the study lived within 5 miles of an air
      pollution monitor. Using logistic regression analyses, we modeled the risk of
      retinoblastoma due to air toxic exposure, separately for exposures in pregnancy
      and the first year of life. With a per interquartile range increase in air toxic
      exposure, retinoblastoma risk was found to be increased with pregnancy exposure
      to benzene (OR=1.67, 95% CI: 1.06, 2.64) and other toxics which primarily arise
      from gasoline and diesel combustion: toluene, 1,3-butadiene, ethyl benzene, ortho
      xylene, and meta/para-xylene; these six toxics were highly correlated.
      Retinoblastoma risk was also increased with pregnancy exposure to chloroform
      (OR=1.35, 95% CI: 1.07, 1.70), chromium (OR=1.29, 95% CI: 1.04, 1.60), para
      dichlorobenzene (OR=1.24, 95% CI: 1.04, 1.49), nickel (OR=1.48, 95% CI: 1.08,
      2.01), and in the first year of life, acetaldehyde (OR=1.62, 95% CI: 1.06, 2.48).
      Sources of these agents are discussed. 

PMID- 24280683
TI  - Bayesian spatiotemporal modelling for the assessment of short-term exposure to
      particle pollution in urban areas.
AB  - This paper describes a Bayesian hierarchical approach to predict short-term
      concentrations of particle pollution in an urban environment, with application to
      inhalable particulate matter (PM10) in Greater London. We developed and compared
      several spatiotemporal models that differently accounted for factors affecting
      the spatiotemporal properties of particle concentrations. We considered two main
      source contributions to ambient measurements: (i) the long-range transport of the
      secondary fraction of particles, which temporal variability was described by a
      latent variable derived from rural concentrations; and (ii) the local primary
      component of particles (traffic- and non-traffic-related) captured by the output
      of the dispersion model ADMS-Urban, which site-specific effect was described by a
      Bayesian kriging. We also assessed the effect of spatiotemporal covariates,
      including type of site, daily temperature to describe the seasonal changes in
      chemical processes affecting local PM10 concentrations that are not considered in
      local-scale dispersion models and day of the week to account for time-varying
      emission rates not available in emissions inventories. The evaluation of the
      predictive ability of the models, obtained via a cross-validation approach,
      revealed that concentration estimates in urban areas benefit from combining the
      city-scale particle component and the long-range transport component with
      covariates that account for the residual spatiotemporal variation in the
      pollution process. 

PMID- 24280685
TI  - MODELING AIRWAY PROBABILITY.
AB  - We present a probability model for lung airways in computed tomography (CT)
      images. Lung airways are tubular structures that display specific features, such
      as low intensity and proximity to vessels and bronchial walls. From these
      features, the posterior probability for the airway feature space was computed
      using a Bayesian model based on 20 CT images from subjects with different degrees
      of Chronic Obstructive Pulmonary Disease (COPD). The likelihood probability was
      modeled using both a Gaussian distribution and a nonparametric kernel density
      estimation method. After exhaustive feature selection, good specificity and
      sensitivity were achieved in a cross-validation study for both the Gaussian
      (0.83, 0.87) and the nonparametric method (0.79, 0.89). The model generalizes
      well when trained using images from a late stage COPD group. This probability
      model may facilitate airway extraction and quantitative assessment of lung
      diseases, which is useful in many clinical and research settings.

PMID- 24280686
TI  - RhoB controls coordination of adult angiogenesis and lymphangiogenesis following
      injury by regulating VEZF1-mediated transcription.
AB  - Mechanisms governing the distinct temporal dynamics that characterize post-natal
      angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation
      remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses
      to growth factors, genotoxic stress and neoplastic transformation. Here we show,
      using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in
      the ischaemic retina and reduces angiogenesis in response to cutaneous wounding,
      but enhances lymphangiogenesis following both dermal wounding and inflammatory
      challenge. We link these unique and opposing roles of RhoB in blood versus
      lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting
      and proliferation in primary human blood versus lymphatic endothelial cells. We
      demonstrate that nuclear RhoB-GTP controls expression of distinct gene sets in
      each endothelial lineage by regulating VEZF1-mediated transcription. Finally, we
      identify a small-molecule inhibitor of VEZF1-DNA interaction that recapitulates
      RhoB loss in ischaemic retinopathy. Our findings establish the first intra
      endothelial molecular pathway governing the phased response of angiogenesis and
      lymphangiogenesis following injury. 

PMID- 24280684
TI  - A comprehensive review of levels and determinants of personal exposure to dust
      and endotoxin in livestock farming.
AB  - The respiratory health effects of livestock farming have been on debate for more
      than three decades. Endotoxin-contaminated organic dusts are considered as the
      most important respiratory hazards within livestock environments. A comprehensive
      review of the knowledge from studies assessing the exposure status of livestock
      farmers is still to be published. The present study reviews research published
      within the last 30 years on personal exposure of livestock farmers to organic
      dust and endotoxin, focusing on studies on pig, poultry and cattle farmers.
      Applied measurement methods and reported levels of personal exposure for the
      total, inhalable and respirable fractions are summarized and discussed, with
      emphasis on the intensity of exposure and the size and distribution of the
      reported exposure variability. In addition, available evidence on potential
      determinants of personal exposure to dust and endotoxin among these farmers are
      documented and discussed, taking results from exposure determinant studies using
      stationary sampling approaches into consideration. Research needs are addressed
      from an epidemiological and industrial hygiene perspective. Published studies
      have been heterogeneous in design, and applied methodologies and results were
      frequently inadequately reported. Despite these limitations and the presence of
      an enormous variability in personal exposure to dust and endotoxin, no clear
      downward trends in exposure with time were observed, suggesting that working
      environments within stables remains largely uncontrolled. Exposure control and
      prevention strategies for livestock farmers are urgently required. These should
      focus on the development of novel and improved methods of controlling dust and
      endotoxin exposure within stables based on the currently available knowledge on
      determinants of exposure. 

PMID- 24280687
TI  - Investigation of the long-term patency of a transmural heparinized
      polycaprolactone and poly(D,L-lactic/glycolic acid) scaffold.
AB  - BACKGROUND: The transmural biodegradable polycaprolactone/poly(D,L
      lactic/glycolic acid) (PCL/PLGA) scaffold is a promising modality for diffuse
      coronary atherosclerosis cases that are not suitable for bypass grafting. The
      purpose of this study was to evaluate the long-term performance of the PCL/PLGA
      scaffold in vivo in the setting of polymer and heparin degradation. MATERIALS AND
      METHODS: After mechanical drilling through the ventricular wall was performed in
      the whole ventricular wall, two scaffolds were implanted into the ventricular
      wall. Animals were grouped into the single drilling group (SD group), the blank
      scaffold group (BS group), and the heparinized scaffold group (HS group) and were
      allowed to survived for 6 mo. Next, the patency and integrity of the scaffolds
      were evaluated by echocardiography and 3D-DOCTOR software. Endothelium coverage
      of the lumen was evaluated by scanning electron microscopy. Neovessels and
      collagen fiber within the scaffolds were identified by histologic staining.
      Metabolite production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the
      plasma was measured by an enzyme-linked immunosorbent assay. The expression
      levels of PGI2 synthase and cyclooxygenase 2 (COX-2) involved in PGI2 production
      and COX-1 involved in TXA2 production were measured by Western blot analysis.
      RESULTS: The heparinized scaffolds were patent for up to 6 mo and the lumen was
      covered with confluent endothelial cells. Histologic staining revealed collagen
      fiber remodeling and reconstruction of the neovascular network immediately
      surrounding the lumen. The expression of PGI2 synthase and COX-2 in the HS group
      was significantly higher compared with the SD and BS groups (P < 0.01). The
      expression of COX-1 was similar in the three groups (P > 0.05). Consistent with
      synthetase expression, a PGI2 metabolite (6-keto-PGF1a) also showed a significant
      increase in the HS group relative to the SD and BS groups (P = 0.021 and P =
      0.015, respectively). Concomitantly, as a PGI2 antagonist, the TXA2 metabolite
      (TXB2) did not exhibit a significant difference among the three groups (P =
      0.17). CONCLUSIONS: Despite polymer and heparin degradation, the scaffold could
      continuously maintain the structural integrity and lumen patency for up to 6 mo
      by reinforcement of host collagen fiber and the balance of PGI2/TXA2.

PMID- 24280688
TI  - De novo frameshift mutation in fibroblast growth factor 8 in a male patient with
      gonadotropin deficiency.
AB  - BACKGROUND/AIMS: Missense, nonsense, and splice mutations in the Fibroblast
      Growth Factor 8(FGF8) have recently been identified in patients with hypothalamo
      pituitary dysfunction and craniofacial anomalies. Here, we report a male patient
      with a frameshift mutation in FGF8. CASE REPORT: The patient exhibited
      micropenis, craniofacial anomalies, and ventricular septal defect at birth.
      Clinical evaluation at 16 years and 8 months of age revealed delayed puberty,
      hyposmia, borderline mental retardation, and mild hearing difficulty. Endocrine
      findings included gonadotropin deficiency and primary hypothyroidism. RESULTS:
      Molecular analysis identified a de novo heterozygous p.S192fsX204 mutation in the
      last exon of FGF8. RT-PCR analysis of normal human tissues detected FGF8
      expression in the genital skin, and whole-mount in situ hybridization analysis of
      mouse embryos revealed Fgf8 expression in the anlage of the penis. CONCLUSION:
      The results indicate that frameshift mutations in FGF8 account for a part of the
      etiology of hypothalamo-pituitary dysfunction. Micropenis in patients with FGF8
      abnormalities appears to be caused by gonadotropin deficiency and defective
      outgrowth of the anlage of the penis.

PMID- 24280689
TI  - Cardiomyopathies: the value of cardiac magnetic resonance imaging.

PMID- 24280691
TI  - Intra-abdominal hypertension in medical critically ill patients: a narrative
      review.
AB  - Intra-abdominal hypertension/abdominal compartment syndrome (IAH/ACS) is a well
      recognized entity among surgical subspecialties. Nevertheless, it has been proven
      to be present in the medical critically ill population. Prospective and
      retrospective observational studies have found medical patients with IAH/ACS to
      be associated with death in the intensive care unit and other poor outcomes.
      Frequently, it is underdiagnosed and undertreated in this patient group.
      Limitations encountered in these observational studies are their small population
      size and single-center design. In addition, most studies target consecutive
      intensive care unit admissions instead of limiting IAH/ACS screening to a
      predefined population confined by their risk factors (unspecified ascites,
      mechanical ventilation, positive fluid balance, etc.). Generally, medical
      patients with IAH/ACS are more severely ill compared with surgical patients.
      Furthermore, they are less likely to receive treatment targeted at lowering intra
      abdominal pressure. Medical treatment of IAH/ACS has not been demonstrated to be
      specifically effective to avoid decompressive surgery. Identifying medical
      patients at risk of IAH represents an underresearched area for which training in
      measurement of abdominal pressure surrogates, awareness of its prevalence, and
      prevention and treatment of such condition could further improve outcomes in
      critically ill medical patients. 

PMID- 24280690
TI  - Plasma colloid osmotic pressure is an early indicator of injury and hemorrhagic
      shock.
AB  - OBJECTIVE: Hemorrhagic shock is the leading cause of traumatic deaths; many could
      be potentially prevented with appropriate resuscitation. However, to initiate
      resuscitation, one must identify patients with hemorrhagic shock early. In this
      article, we determined the associations between plasma colloid osmotic pressure
      (COP) and clinical outcomes in severely injured trauma patients. METHODS: Plasma
      samples were collected from 104 trauma patients upon admission to the emergency
      department and 10 healthy volunteers to serve as control subjects. Plasma
      osmolality, COP, and serum protein were measured and correlated to clinical data.
      Thrombelastography and impedance aggregometry were performed to assess
      coagulopathy. Commercial enzyme-linked immunosorbent assays were used to quantify
      syndecan 1. RESULTS: Plasma COP was significantly reduced in trauma patients
      compared to control subjects 17.7 +/- 2.6 vs. 20.7 +/- 2.1 mmHg (P < 0.05) and
      strongly correlated to serum protein values (R = 0.7). We divided our cohort into
      low (COP <=16.5 mmHg) and normal (COP >16.5 mmHg) subgroups, illustrating
      significantly higher Injury Severity Score scores in patients with low COP (21
      vs. 10, P = 0.007), despite no differences in vital signs. Patients with low COP
      received more red blood cells, plasma, and platelets (4 vs. 0 total units, P =
      0.0005) within 24 h of admission. Syndecan 1 levels were significantly higher
      (184 vs. 52 ng/mL, P = 0.027) in patients with low COP. CONCLUSIONS: Reduced
      plasma COP and serum protein in trauma patients are indicative of injury
      severity. In the absence of significant alterations in vital signs, plasma COP
      levels were associated with increased requirements for blood products and
      increased syndecan 1 shedding. We believe that plasma COP provides new insight in
      guiding resuscitation.

PMID- 24280692
TI  - Modulation of breathing behavior of layered coordination polymers via a solid
      solution approach: the influence of metal ions on sorption behavior.
AB  - Four iso-structural layered coordination polymers (CPs) of Cd(II) and Zn(II) were
      shown to exhibit breathing transitions with N2/H2 gases. Furthermore, the solid
      solutions containing Zn(II)/Cd(II) have shown better uptake capacities of gas
      than parent CPs. These results give some insights into the role of metal ions and
      anions for fine-tuning the porosity of CPs.

PMID- 24280694
TI  - A cluster analytic study of the Wechsler Intelligence Test for Children-IV in
      children referred for psychoeducational assessment due to persistent academic
      difficulties.
AB  - Wechsler Intelligence Test for Children-IV core subtest scores of 472 children
      were cluster analyzed to determine if reliable and valid subgroups would emerge.
      Three subgroups were identified. Clusters were reliable across different stages
      of the analysis as well as across algorithms and samples. With respect to
      external validity, the Globally Low cluster differed from the other two clusters
      on Wechsler Individual Achievement Test-II Word Reading, Numerical Operations,
      and Spelling subtests, whereas the latter two clusters did not differ from one
      another. The clusters derived have been identified in studies using previous WISC
      editions. Clusters characterized by poor performance on subtests historically
      associated with the VIQ (i.e., VCI + WMI) and PIQ (i.e., POI + PSI) did not
      emerge, nor did a cluster characterized by low scores on PRI subtests. Picture
      Concepts represented the highest subtest score in every cluster, failing to vary
      in a predictable manner with the other PRI subtests.

PMID- 24280693
TI  - Allergens are not pathogens: why immunization against allergy differs from
      vaccination against infectious diseases.
AB  - Vaccination against infectious diseases has been one of the major breakthroughs
      in human medical history, saving the lives of millions of people each year. More
      recently, prophylactic vaccination against non-infectious diseases such as
      cancer, Alzheimer's disease, diabetes, and type I allergy is being investigated.
      Particularly in case of IgE-driven allergic disorders, which afflict almost a
      quarter of the population in highly developed countries, preventative measures
      would represent a major improvement for patients' health as well as an economic
      relief for public health services. As an alternative to allergen-specific
      immunotherapy, prophylactic vaccination against type I allergic diseases could
      slow down or even stop the progress of the allergy pandemic. Allergen-encoding
      gene-based vaccines, i.e., plasmid DNA and mRNA vaccines, provide the advantage
      of purity over crude allergen extracts, which involve the risk of de novo
      sensitizations. Furthermore, these formulations have been demonstrated to induce
      T helper 1 as well as T regulatory immune responses--a pre-requisite for
      prophylactic intervention against allergies. However, prophylactic vaccines
      against environmental allergens strikingly differ from conventional vaccines
      against infectious diseases or therapeutic approaches concerning the underlying
      immunological mechanisms.

PMID- 24280695
TI  - Dietary reconstruction of Pliocene Parapapio whitei from Makapansgat, South
      Africa, using dental microwear texture analysis.
AB  - Pliocene Parapapio whitei fossils from Makapansgat have yielded stable isotope
      values suggesting some foraging on C4 plants and possibly underground storage
      organs (USOs). Dental microwear texture analysis on Pp.whitei (M 3147, MP 62, MP
      223 and MP 239) from Makapansgat Members 3-4 is performed to examine whether
      tooth surface damage from mastication agrees with prior dietary inferences from
      isotopes. The enamel surface texture of Pp. whitei is relatively complex,
      resembling Lophocebus albigena and Cebusapella, and lacks the anisotropy of
      Trachypithecuscristatus and Alouattapalliata. The textural fill volume of Pp.
      whitei is distinct from extant forest primates suggesting extremes in hard-object
      consumption. Grit adhering to USOs is offered as an explanation for these enamel
      textural properties, corroborating the inference that Pp. whitei supplemented its
      diet with terrestrial resources. (c) 2013 S. Karger AG, Basel. 

PMID- 24280696
TI  - Hsp90 inhibitors and the reduction of anti-cancer drug resistance by non-genetic
      and genetic mechanisms.
AB  - In this review, we focus on how inhibitors of Hsp90 can help prevent the
      resistance to anti-cancer drugs by synergistically increasing their cancer
      killing abilities and thereby allowing them to function at much lower
      concentrations than normally used. Hsp90 helps to fold numerous client proteins,
      such as Akt, Raf, Src, chromatin-modifying proteins, nuclear hormone receptors,
      and kinetochore assembly proteins. We discuss four mechanisms by which Hsp90
      inhibitors can potentially synergize with anti-cancer drugs: by making a drug
      resistant protein that is a client for Hsp90 more sensitive to the drug, by
      increasing chromosomal aneuploidy and the effectiveness of DNA-damaging drugs, by
      inhibiting Trithorax proteins which trimethylate histone 3 at lysine 4 (H3K4me3)
      and thereby decreasing expression of tumor promoter genes, and by interacting
      with the negative elongation factor (NELF) complex in tumors. We also explain how
      the evolutionary capacitor function of Hsp90 can be exploited with inhibitors of
      Hsp90 by exposing new protein variants that can be targeted with other drugs,
      thereby opening new avenues of combination drug therapy to treat cancer. We
      believe that inhibition of these processes can increase the efficacy of Hsp90
      inhibitors with other anti-cancer drugs. 

PMID- 24280697
TI  - The tissue selective estrogen complex: a promising new menopausal therapy.
AB  - Menopause is associated with health concerns including vasomotor symptoms,
      vulvar/vaginal atrophy (VVA), and osteoporosis. Estrogen therapy or combined
      estrogen-progestin therapy (EPT) are primary treatment options for menopausal
      symptom relief and osteoporosis prevention. Because EPT has been associated with
      some safety/tolerability concerns relating to undesirable effects of estrogen and
      progestin, alternative options are needed. The tissue selective estrogen complex
      (TSEC) is a novel class of agents pairing a selective estrogen receptor modulator
      (SERM) with 1 or more estrogens. The TSEC combines the established efficacy of
      estrogens on menopausal symptoms and bone with the protective effects of a SERM
      on the reproductive tract. The pairing of bazedoxifene (BZA) with conjugated
      estrogens (CE) has been evaluated in a series of phase 3 clinical trials. BZA 20
      mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg have shown efficacy in reducing the
      frequency and severity of hot flushes, relieving VVA symptoms, and maintaining
      bone mass while protecting the endometrium and breast. These BZA/CE doses have
      been associated with a favorable safety/tolerability profile, with higher rates
      of cumulative amenorrhea and lower incidences of breast pain than those reported
      for EPT. Thus, BZA/CE may be a promising alternative to conventional EPT for
      treating non-hysterectomized, postmenopausal women. 

PMID- 24280698
TI  - Differential cellular and molecular effects of butyrate and trichostatin a on
      vascular smooth muscle cells.
AB  - The histone deacetylase (HDAC) inhibitors, butyrate and trichostatin A (TSA), are
      epigenetic histone modifiers and proliferation inhibitors by downregulating
      cyclin D1, a positive cell cycle regulator, and upregulating p21Cip1 and INK
      family of proteins, negative cell cycle regulators. Our recent study indicated
      cyclin D1 upregulation in vascular smooth muscle cells (VSMC) that are
      proliferation-arrested by butyrate. Here we investigate whether cyclin D1
      upregulation is a unique response of VSMC to butyrate or a general response to
      HDAC inhibitors (HDACi) by evaluating the effects of butyrate and TSA on VSMC.
      While butyrate and TSA inhibit VSMC proliferation via cytostatic and cytotoxic
      effects, respectively, they downregulate cdk4, cdk6, and cdk2, and upregulate
      cyclin D3, p21Cip1 and p15INK4B, and cause similar effects on key histone H3
      posttranslational modifications. Conversely, cyclin D1 is upregulated by butyrate
      and inhibited by TSA. Assessment of glycogen synthase 3-dependent
      phosphorylation, subcellular localization and transcription of cyclin D1
      indicates that differential effects of butyrate and TSA on cyclin D1 levels are
      linked to disparity in cyclin D1 gene expression. Disparity in butyrate- and TSA
      induced cyclin D1 may influence transcriptional regulation of genes that are
      associated with changes in cellular morphology/cellular effects that these HDACi
      confer on VSMC, as a transcriptional modulator. 

PMID- 24280699
TI  - Molecular dynamics simulations of hsp90 with an eye to inhibitor design.
AB  - Proteins carry out their functions through interactions with different partners.
      Dynamic conformational switching among different structural sub-states favors the
      adaptation to the shapes of the different partners. Such conformational changes
      can be determined by diverse biochemical factors, such as ligand-binding. Atomic
      level investigations of the mechanisms that underlie functional dynamics may
      provide new opportunities for the discovery of leads that target disease-related
      proteins. In this review, we report our views and approaches on the development
      of novel and accurate physical-chemistry-based models for the characterization of
      the salient aspects of the ligand-regulated dynamics of Hsp90, and on the
      exploitation of such new knowledge for the rational discovery of inhibitors of
      the chaperone. 

PMID- 24280701
TI  - Applications of cell-penetrating peptides for tumor targeting and future cancer
      therapies.
AB  - Cell-penetrating peptides provide a highly promising strategy for intracellular
      drug delivery. One relevant clinical application of cell-penetrating peptides is
      cancer therapeutics. Peptide based delivery could increase the uptake of drugs in
      tumor cells and thereby increase the efficacy of the treatment, either of
      conventional small molecular drugs or oligonucleotide based therapeutics. This
      review is focused on the cancer applications of cell penetrating peptides as
      delivery systems; different aspects of drug loading, cargoes and delivery are
      discussed together with methods for targeted delivery, activatable cell
      penetrating peptides and transducible agents coupled to cell-penetrating
      peptides. 

PMID- 24280700
TI  - Epigenetic control and cancer: the potential of histone demethylases as
      therapeutic targets.
AB  - The development of cancer involves an immense number of factors at the molecular
      level. These factors are associated principally with alterations in the
      epigenetic mechanisms that regulate gene expression profiles. Studying the
      effects of chromatin structure alterations, which are caused by the
      addition/removal of functional groups to specific histone residues, are of great
      interest as a promising way to identify markers for cancer diagnosis, classify
      the disease and determine its prognosis, and these markers could be potential
      targets for the treatment of this disease in its different forms. This manuscript
      presents the current point of view regarding members of the recently described
      family of proteins that exhibit histone demethylase activity; histone
      demethylases are genetic regulators that play a fundamental role in both the
      activation and repression of genes and whose expression has been observed to
      increase in many types of cancer. Some fundamental aspects of their association
      with the development of cancer and their relevance as potential targets for the
      development of new therapeutic strategies at the epigenetic level are discussed
      in the following manuscript. 

PMID- 24280702
TI  - Heat shock protein 90 (hsp90) expression and breast cancer.
AB  - Hsp90 is an abundant protein in mammalian cells. It forms several discrete
      complexes, each containing distinct groups of co-chaperones that assist protein
      folding and refolding during stress, protein transport and degradation. It
      interacts with a variety of proteins that play key roles in breast neoplasia
      including estrogen receptors, tumor suppressor p53 protein, angiogenesis
      transcription factor HIF-1alpha, antiapoptotic kinase Akt, Raf-1 MAP kinase and a
      variety of receptor tyrosine kinases of the erbB family. Elevated Hsp90
      expression has been documented in breast ductal carcinomas contributing to the
      proliferative activity of breast cancer cells; whilst a significantly decreased
      Hsp90 expression has been shown in infiltrative lobular carcinomas and lobular
      neoplasia. Hsp90 overexpression has been proposed as a component of a mechanism
      through which breast cancer cells become resistant to various stress stimuli.
      Therefore, pharmacological inhibition of HSPs can provide therapeutic
      opportunities in the field of cancer treatment. 17-allylamino,17
      demethoxygeldanamycin is the first Hsp90 inhibitor that has clinically been
      investigated in phase II trial, yielding promising results in patients with HER2
      overexpressing metastatic breast cancer, whilst other Hsp90 inhibitors
      (retaspimycin HCL, NVP-AUY922, NVP-BEP800, CNF2024/BIIB021, SNX-5422, STA-9090,
      etc.) are currently under evaluation. 

PMID- 24280703
TI  - Why and How the Old Neuroleptic Thioridazine Cures the XDR-TB Patient.
AB  - This mini-review provides the entire experimental history of the development of
      the old neuroleptic thioridazine (TZ) for therapy of antibiotic resistant
      pulmonary tuberculosis infections. TZ is effective when used in combination with
      antibiotics to which the initial Mycobacterium tuberculosis was resistant. Under
      proper cardiac evaluation procedures, the use of TZ is safe and does not produce
      known cardiopathy such as prolongation of QT interval. Because TZ is cheap, it
      should be considered for therapy of XDR and TDR-Mtb patients in economically
      disadvantaged countries. 

PMID- 24280704
TI  - Evaluation of the Combined Effects of Stilbenoid from Shorea gibbosa and
      Vancomycin against Methicillin-Resistant Staphylococcus aureus (MRSA).
AB  - The aim of this study is to determine the combined effects of stilbenoids from
      Shorea gibbosa and vancomycin against methicillin-resistant Staphylococcus aureus
      (MRSA). A total of nine pure compounds, five stilbenoid dimers epsilon-viniferin,
      ampelopsin A, balanocarpol, laevifonol and diptoindonesin G and four stilbenoid
      trimers a-viniferin, johorenol A, ampelopsin E and vaticanol G were evaluated for
      their antibacterial activities against ATCC 33591 and a HUKM clinical isolate.
      Minimum inhibitory concentration (MIC) and minimum bactericidal concentration
      (MBC) for each active compound were determined using the serial microdilution and
      plate-streak techniques. The combined effect of stilbenoids with vancomycin
      against MRSA was evaluated using the checkerboard assay to determine their
      fractional inhibitory concentration (FIC) index values. The MIC value of a
      viniferin on both MRSA strains was 100 MUg/mL, whereas those of johorenol A on
      ATCC 33591 and HUKM strain were 100 MUg/mL and 200 MUg/mL, respectively. The MIC
      values of ampelopsin E and vaticanol G were higher than 400 MUg/mL. Out of the
      five stilbenoid dimers, only epsilon-viniferin was capable of inhibiting the
      growth of both MRSA strains at MIC 400 MUg/mL. The MBC value of epsilon
      viniferin, a-viniferin and johorenol A showed bacteriostatic action against MRSA.
      The FIC index value of epsilon-viniferin and a-viniferin in combination with
      vancomycin showed an additive effect (0.5 < FIC <= 2.0) against both MRSA
      strains. Johorenol A-vancomycin combination was also additive against HUKM
      strain, but it showed synergistic interaction with vancomycin against ATCC 33591
      (FIC < 0.5). Stilbenoid compounds from Shorea gibbosa have anti-MRSA activity and
      huge potential as an alternative phytotherapy in combating MRSA infections. 

PMID- 24280705
TI  - Association analysis of the IL2RA gene with alopecia areata in a Chinese
      population.
AB  - BACKGROUND: Interleukin-2 receptor subunit alpha (IL2RA) is highly expressed on
      CD4+CD25+ regulatory T cells and is important for immune homeostasis and the
      suppression of autoimmune responses. It has been suggested that the single
      nucleotide polymorphism in IL2RA may affect the pathogenesis of alopecia areata
      (AA). OBJECTIVE: Our aim was to investigate the link between IL2RA polymorphism
      and AA in a Chinese population. METHODS: We examined 427 patients and 430
      controls in this study. The rs3118470 polymorphism was evaluated using high
      resolution melting analysis and direct sequencing. RESULTS: The prevalence of the
      C/C, T/C and T/T genotypes was 16.2, 48.2 and 35.6%, respectively. The genotype
      distribution and allele frequencies were significantly different between AA and
      control subjects (p < 0.0001). The C allele frequency was significantly higher in
      the AA group (p < 0.0001), and the frequencies of C allele and C/C genotype were
      higher in the patients with family history (p = 0.034; p < 0.0001). CONCLUSIONS:
      The rs3118470 single nucleotide polymorphism of IL2RA may be a genetic marker to
      assess the risk of AA in a Chinese population.

PMID- 24280706
TI  - Nano boron nitride flatland.
AB  - Recent years have witnessed many breakthroughs in research on two-dimensional
      (2D) nanomaterials, among which is hexagonal boron nitride (h-BN), a layered
      material with a regular network of BN hexagons. This review provides an insight
      into the marvellous nano BN flatland, beginning with a concise introduction to BN
      and its low-dimensional nanostructures, followed by an overview of the past and
      current state of research on 2D BN nanostructures. A comprehensive review of the
      structural characteristics and synthetic routes of BN monolayers, multilayers,
      nanomeshes, nanowaves, nanoflakes, nanosheets and nanoribbons is presented. In
      addition, electronic, optical, thermal, mechanical, magnetic, piezoelectric,
      catalytic, ecological, biological and wetting properties, applications and
      research perspectives for these novel 2D nanomaterials are discussed. 

PMID- 24280707
TI  - Maternal separation induces alterations in reversal learning and brain-derived
      neurotrophic factor expression in adult rats.
AB  - AIMS: Early postnatal maternal and/or sibling separation (MS) can play an
      important role in the development of psychopathologies during ontogeny. The
      purpose of the present study is to investigate the effects of repeated MS on the
      cognitive and brain-derived neurotrophic factor (BDNF) function of rats. METHODS:
      We investigated the effects of repeated MS that lasted 3 h/day during postnatal
      days 1-21 on spatial learning and reversal learning in Morris water maze tests in
      male rats. The rats were tested in 4 trials. Moreover, we examined the effects of
      MS on BDNF protein expression in the medial prefrontal cortex (mPFC), the nucleus
      accumbens, and the hippocampus via immunohistochemistry measurements. RESULTS: We
      found that repeated MS modestly disrupted reversal learning performance in the
      Morris water maze and decreased BDNF protein expression in the mPFC. CONCLUSION:
      The present study enhances our understanding of the neurobiological and
      behavioral consequences of repeated episodes of MS in rats to some degree.

PMID- 24280708
TI  - Are new TiNbZr alloys potential substitutes of the Ti6Al4V alloy for dental
      applications? An electrochemical corrosion study.
AB  - The main aim of this work was to assess the electrochemical behavior of new
      Ti35Nb5Zr and Ti35Nb10Zr alloys in artificial saliva at 37  degrees C to verify
      if they are indicated to be used as biomaterials in dentistry as alternatives to
      Ti6Al4V alloys in terms of corrosion protection efficiency of the material.
      Electrochemical impedance spectroscopy (EIS) experiments were carried out for
      different periods of time (0.5-216 h) in a three-electrode cell, where the
      working electrode (Ti alloys) was exposed to artificial saliva at 37  degrees C.
      The near-surface region of the alloys was investigated using x-ray photoelectron
      spectroscopy (XPS). All alloys exhibited an increase in corrosion potential with
      the immersion time, indicating the growth and stabilization of the passive film.
      Ti35Nb5Zr and Ti6Al4V alloys had their EIS results interpreted by a double-layer
      circuit, while the Ti35Nb10Zr alloy was modeled by a one-layer circuit. In
      general, the new TiNbZr alloys showed similar behavior to that observed for the
      Ti6Al4V. XPS results suggest, in the case of the TiNbZr alloys, the presence of a
      thicker passive layer containing a lower fraction of TiO2 phase than that of
      Ti6Al4V. After long-term immersion, all alloys develop a calcium phosphate phase
      on the surface. The new TiNbZr alloys appear as potential candidates to be used
      as a substitute to Ti6Al4V in the manufacturing of dental implant-abutment sets. 

PMID- 24280709
TI  - Postoperative complications and association with outcomes in pediatric cardiac
      surgery.
AB  - OBJECTIVE: Our primary aim was to study postoperative complications in pediatric
      cardiac surgery patients and their association with cardiopulmonary bypass (CPB)
      use. The secondary aim was to evaluate the association of postoperative
      complications with established outcome measures. METHODS: A single-institution
      retrospective observational study was undertaken of consecutive pediatric cardiac
      surgery patients during a 1-year period. Five cardiac and 15 extracardiac
      complications were studied. CPB use, CPB parameters, demographics, and Risk
      Adjusted Classification for Congenital Heart Surgery (RACHS-1) levels were
      evaluated as risk factors for complications. Outcomes, including mechanical
      ventilation duration, pediatric cardiac intensive care unit stay, hospital stay,
      and mortality were studied. RESULTS: A total of 325 patients were studied: 271
      with CPB and 54 without CPB. Of the 325 patients, 141 (43%) had >=1 complication
      (95% confidence interval, 38%-49%). Of the 325 patients, 82 (25%) developed
      cardiac and 120 (37%) developed extracardiac complications. The evidence from
      logistic regression analysis was insufficient to suggest a relationship between
      CPB support and the incidence of cardiac or extracardiac complications after
      adjusting for age, gender, previous sternotomy, and RACHS-1 levels. For patients
      receiving CPB, longer CPB times, higher RACHS-1 levels, and a lower temperature
      with CPB were associated with a greater number of cardiac complications (P <
      .01). Longer CPB times and higher RACHS-1 levels were associated with a greater
      number of extracardiac complications (P = .006). Postoperative complications were
      significantly associated with an increased mechanical ventilation duration,
      pediatric cardiac intensive care unit stay, and hospital stay and mortality (P <
      .01). CONCLUSIONS: Postoperative complications occurred in 43% of pediatric
      cardiac surgeries performed both with and without CPB. The complications were
      associated with longer mechanical ventilation and pediatric cardiac intensive
      care unit and hospital stays, and increased mortality.

PMID- 24280710
TI  - Role of myocardial hypertrophy on acute and chronic right ventricular performance
      in relation to chronic volume overload in a porcine model: relevance for the
      surgical management of tetralogy of Fallot.
AB  - OBJECTIVES: The age for correction of tetralogy of Fallot has progressively
      declined to the postnatal period, often despite an increased rate of transannular
      patch repair. However, the long-term effect of premature exposure to chronic
      pulmonary insufficiency on the right ventricle remains unknown. On the basis of
      the relationship between the duration of pressure overload and age, the role of
      previous pressure load-related hypertrophy on right ventricular (RV) performance
      after chronic volume overload was investigated in a porcine model. METHODS: RV
      hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with
      (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The
      effect of volume overload was compared between these 2 groups and pigs without
      RVH but with PI and controls (sham). Both acute and chronic effects on RV
      function were studied using conductance technology and validated using
      echocardiography. RESULTS: After chronic volume overload, the end-systolic and
      end-diastolic volumes were smaller in the RVH+PI group than in the PI group,
      including a lower pulmonary regurgitation fraction (25% +/- 5% vs 35% +/- 5%; P =
      .002). RVH resulted in better preserved systolic function, confirmed by an
      increased preload recruitable stroke work slope (14.7 +/- 1.8 vs 9.3 +/- 1.3
      Mw.s/mL; P = .025) and higher RV ejection fraction (51% +/- 3% vs 45% +/- 4%; P =
      .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group
      (beta, 0.19 +/- 0.03 vs 0.12 +/- 0.02 mL(-1); P = .001), presenting restrictive
      physiology only in the condition associating RVH and PI. CONCLUSIONS: The results
      of the present study have demonstrated that RVH attenuates the RV remodeling
      process related to chronic PI. It enables better preservation of contractility
      but at the cost of sustained diastolic impairment. These findings might help to
      determine the timing and strategy for repair of tetralogy of Fallot when RV
      outflow tract morphology indicates a definite need for transannular
      reconstruction.

PMID- 24280711
TI  - Total arch repair with open triple-branched stent graft placement for acute type
      A aortic dissection: experience with 122 patients.
AB  - OBJECTIVE: To summarize the clinical experiences and midterm follow-up results of
      total arch repair with open triple-branched stent graft placement for acute type
      A aortic dissection. METHODS: From June 2008 to March 2013, 122 patients (95 men
      and 27 women; mean age, 50.9 +/- 10.4 years) with acute type A aortic dissection
      underwent total arch repair with open placement of a triple-branched stent graft
      under hypothermic cardiopulmonary bypass and selective cerebral perfusion. During
      the follow-up period, enhanced computed tomography and echocardiography were
      performed at 3 months postoperatively and annually thereafter. RESULTS: Placement
      of the triple-branched stent graft into the true lumen of the descending aorta,
      arch, and 3 arch vessels was technically successful in 121 patients. The
      cardiopulmonary bypass time was 186.50 +/- 38.23 minutes, and the selective
      antegrade cerebral perfusion time was 31.97 +/- 10.08 minutes. The in-hospital
      mortality was 4.93%. No permanent neurologic dysfunction or paraplegia was
      observed. Three patients were lost to follow-up. The mean follow-up period was
      30.24 +/- 12.35 months. After hospital discharge, 3 patients died. On the 3-month
      postoperative scans, complete thrombus formation around the triple-branched stent
      graft was observed in 89.38% of the patients. Endoleaks were detected in 12
      patients; 8 patients refused any management for the endoleaks, but they
      maintained a good quality of life. The other 4 patients were successfully treated
      by additional surgery. CONCLUSIONS: Total arch repair with open triple-branched
      stent graft placement is an effective technique with satisfactory early and
      midterm results. This technique could be an attractive alternative to
      conventional total arch replacement.

PMID- 24280712
TI  - Sutureless replacement versus transcatheter valve implantation in aortic valve
      stenosis: a propensity-matched analysis of 2 strategies in high-risk patients.
AB  - OBJECTIVE: This propensity-matched study compared clinical and echocardiographic
      outcomes between patients undergoing transcatheter aortic valve implantation
      (TAVI) and sutureless aortic valve replacement. METHODS: From January 2010 to
      March 2012, 122 patients (age 79.4 +/- 5.3 years, logistic euroSCORE 12% +/-
      8.4%) underwent minimally invasive sutureless aortic valve replacement, and 122
      (age 84.6 +/- 6.2 years, logistic euroSCORE 20.9% +/- 2.5%) underwent TAVI. After
      propensity matching, 37 matched pairs were available for analysis. RESULTS:
      Preoperative characteristics and risk scores of matched groups were comparable.
      In-hospital mortalities were 0% in the sutureless group and 8.1% (n = 3) in the
      TAVI group (P = .24). Permanent pacemaker implantation was required in 4 patients
      in the sutureless group and 1 patient in the TAVI group (10.8% vs 2.7%; P = .18).
      A neurologic event was recorded in 2 patients of each group. Predischarge
      echocardiographic data showed higher paravalvular leak rate in the TAVI group
      (13.5% vs 0%; P = .027). At mean follow-up of 18.9 +/- 10.1 months, overall
      cumulative survival was 91.9% and significantly differed between groups
      (sutureless 97.3% vs TAVI 86.5%; P = .015). In the TAVI group, a significant
      difference in mortality was observed between patients with (n = 20) and without
      (n = 17) paravalvular leak (25% vs 0%; P = .036). CONCLUSIONS: Combining the
      advantage of standard diseased valve removal with shorter procedural times,
      minimally invasive sutureless aortic valve replacement may be the first-line
      treatment for high-risk patients considered in the "gray zone" between TAVI and
      conventional surgery.

PMID- 24280713
TI  - The incidence of vasoplegia in adult patients with right-sided congenital heart
      defects undergoing cardiac surgery and the correlation with serum vasopressin
      concentrations.
AB  - BACKGROUND: In adults with right-sided congenital heart disease, vasoplegia
      during and after cardiopulmonary bypass appears to be a frequent complication.
      The incidence of vasoplegia in the general adult and pediatric cardiac surgical
      population has been investigated, but the incidence in adult patients with right
      sided congenital heart disease is unknown. Perioperative vasopressin levels
      during cardiac surgery have been studied in other cardiac surgical patients, but
      are not known in adults with right-sided congenital heart disease. The purpose of
      this study was to investigate the incidence of vasoplegia in adult patients
      undergoing right-sided cardiac surgical procedures requiring cardiopulmonary
      bypass and to determine the vasopressin response to cardiac surgery in this
      population. METHODS: Twenty patients were enrolled and demographic, hemodynamic,
      cardiopulmonary bypass, and use of vasoactive medication data were collected. In
      addition, perioperative serum vasopressin levels were measured. Sixty adult
      patients undergoing left-sided cardiac surgery served as controls. RESULTS: The
      incidence of vasoplegia in the control patients was 10% and the incidence in the
      adult patients with right-sided congenital heart disease was 20%. Vasopressin
      levels were low at baseline (0.5 +/- 0.5 pg/mL), increased slightly after
      induction of anesthesia (0.6 +/- 0.6 pg/mL), increased after initiation of
      cardiopulmonary bypass (99.7 +/- 168.2 pg/mL), and decreased after surgery (31.3
      +/- 43.6 pg/mL). CONCLUSIONS: This study showed that the incidence of vasoplegia
      (20%) in patients with right-sided congenital heart disease undergoing cardiac
      surgery was double that of a population of patients undergoing aortic valve
      surgery (10%). Serum vasopressin concentration was not associated with vasoplegia
      in this population of congenital cardiac surgical patients.

PMID- 24280714
TI  - Natural history of hypercoagulability in patients undergoing coronary
      revascularization and effect of preoperative myocardial infarction.
AB  - OBJECTIVES: The balance between hyper- and hypocoagulable states is critical
      after coronary artery surgery both with (coronary artery bypass grafting [CABG])
      and without (off-pump coronary artery bypass [OPCAB]) cardiopulmonary bypass to
      prevent thrombotic or bleeding complications. We aimed to quantify novel
      parameters of coagulation, fibrinolysis, and overall hemostasis <=6 months after
      CABG and OPCAB and to determine the influences on these parameters. METHODS: A
      total of 63 patients (30 CABG, 33 OPCAB) had blood collected before and at
      various points <=6 months after surgery. Fibrin and fibrinolysis time curves were
      generated by measuring the absorption of 405 nm each minute for 100 minutes after
      the addition of tissue factor and tissue plasminogen activator to cell-free
      plasma. The parameters were compared with those from a group of healthy controls.
      RESULTS: The patients' preoperative prothrombotic assay parameters were compared
      with those from healthy controls. Both CABG and OPCAB patients were
      hypercoagulable until at least day 10 after surgery, with elevation of fibrin
      generation (CABG, peak day 3, +28.9%; OPCAB, peak day 1, +16.3% vs preoperative
      baseline) and impairment of fibrinolysis capacity (CABG, day 1, -58.4%; OPCAB,
      day 1, -22.6%). Surgical revascularization resulted in resolution of preoperative
      hypercoagulability by 6 months postoperatively. Patients with preoperative
      myocardial infarction (MI) had prolonged hypercoagulability after surgery that
      was most exaggerated after CABG (overall hemostatic potential day 5, no MI,
      +64.1% vs with MI, +128.9% compared with baseline; P = .013). CONCLUSIONS:
      Patients will be vulnerable to thrombotic events for <=6 weeks after coronary
      surgery yet will have resolution of hypercoagulability by 6 months. Preoperative
      factors, such as MI, could require individualized management of thrombosis
      prophylaxis in the postoperative period.

PMID- 24280715
TI  - Bilateral pulmonary arterial banding results in an increased need for subsequent
      pulmonary artery interventions.
AB  - OBJECTIVE: Despite increasing use of bilateral branch pulmonary artery banding
      (bPAB), both as a temporary stabilizing treatment and as part of comprehensive
      hybrid management of hypoplastic left heart syndrome, little is known about the
      long-term outcomes of the pulmonary arteries (PAs) in banded patients. PATIENTS
      AND METHODS: We conducted a retrospective review of all patients with ductal
      dependent systemic circulation (2001-2013) undergoing bPAB placement at a single
      institution (bPAB, n = 50); patients who underwent a stage I Norwood procedure
      (Norwood, n = 53) were used for comparison. The need for PA interventions
      (surgical arterioplasty, balloon angioplasty, and stent implantation) and PA
      growth were assessed. RESULTS: Bands were in place for a median of 76 days. PA
      growth and size were similar between groups, but bPAB patients required more
      interventions (1.4 +/- 2.9 vs 0.5 +/- 1.2, P = .01). In competing risks analysis,
      only 20% of bPAB patients were alive and free from intervention at 5 years after
      bPAB removal. Multivariable Cox proportional hazards regression of operative
      interventions within the bPAB group demonstrated the following risk factors:
      subsequent 2-ventricle repairs (hazard ratio [HR], 2.2; 95% confidence interval
      [CI], 0.7-6.7), smallest band diameter (HR per additional millimeter, 0.059; 95%
      CI, 0.004-0.849), and duration of band placement more than 90 days (HR, 3.5; 95%
      CI, 1.0-12.6). Hemodynamics and Fontan candidacy did not differ between groups.
      CONCLUSIONS: Patients with bPAB require additional interventions at earlier time
      points than Norwood patients. Patients with smaller bands and longer duration of
      banding are at high risk. Despite stenoses requiring additional interventions,
      Fontan candidacy is maintained.

PMID- 24280716
TI  - Standardizing definitions for hybrid coronary revascularization.

PMID- 24280717
TI  - Repair of naphthalene-induced acute tracheal injury by basal cells depends on
      beta-catenin.
AB  - OBJECTIVES: Little is known about the role of Wnt/beta-catenin in postnatal
      airway homeostasis and basal cell function. This study aimed to investigate the
      role of Wnt signaling in the self-renewal of basal cells and the involvement of
      beta-catenin in tracheal repair after naphthalene-induced injury. METHODS: Mice
      were treated with naphthalene and injected with 4-hydroxytamoxifen. Injury and
      repair of the tracheal epithelium after naphthalene-mediated secretory cell
      depletion was assessed by a immunohistochemical study. The involvement of Wnt and
      beta-catenin signaling in basal cell proliferation was investigated during in
      vitro expansion. RESULTS: Immunohistochemical analysis of tracheal epithelium in
      wild-type mice showed a reduction in the number of Clara cell secretory protein
      (CCSP+) and forkhead box transcription factor (Fox-J1+) cells on days 2 to 5
      after naphthalene-induced injury; this cell population was regenerated by day 10.
      After flush labeling, bromodeoxyuridine-positive (BrdU+) cells and Ki67+ cells
      were observed in tracheal epithelium on days 2 to 5 but not on days 10 and 21.
      Confocal microscopy visualizing K5+ and BrdU+ cells showed that Wnt3a promotes
      proliferation of K5+ cells. Immunohistochemical analysis of K5+ and CCSP+ in
      tracheal epithelial cells from wild-type littermate and K5-Cre-mediated beta
      catenin knock-out mice showed that on day 3, the number of CCSP+ cells was
      decreased in all mice. On day 10, CCSP+ cells were present in wild-type
      littermate mice but absent in conditional knock-out mice. CONCLUSIONS: Basal
      cells serve as stem cells in the tracheal epithelium, regenerating and
      maintaining tracheal epithelial cells in a mouse model of tracheal injury. beta
      Catenin is required for proliferation and self-renewal of tracheal epithelial
      cells.

PMID- 24280718
TI  - Trends in Fontan surgery and risk factors for early adverse outcomes after Fontan
      surgery: the Australia and New Zealand Fontan Registry experience.
AB  - OBJECTIVES: This study examined changes in practice and analyzed risk factors for
      adverse early outcomes after Fontan surgery through use of a binational,
      population-based registry. METHODS: Demographic, preoperative, and perioperative
      data were collected from all participating institutions of the Australia and New
      Zealand Fontan Registry. Patient and operative characteristics were analyzed with
      multivariable logistic regression for impact on early mortality, early Fontan
      failure (death, takedown, or mechanical support), effusions (prolonging hospital
      stay >30 days or requiring surgical reintervention), and stay longer than 30
      days. RESULTS: Overall mortality was 3.5% (37/1071) and declined throughout the
      study period, from 8% (1975-1990) to 4% (1991-2000) and 1% (2001-2010). There
      were no differences between the extracardiac and lateral tunnel modifications for
      any outcome. After 2006, the extracardiac conduit was performed exclusively, with
      1.3% mortality. The proportion of patients with hypoplastic left heart syndrome
      rose to 17% in the current era, and this group had more effusions (odds ratio,
      3.0; 95% confidence interval, 1.4-6.6) and stayed on average 2 days longer in the
      hospital. Hypoplastic left heart syndrome was also an independent risk factor for
      composite adverse early outcome (death, failure, prolonged effusions, or
      prolonged stay >30 days; odds ratio, 2.6; 95% confidence interval 1.4-4.8
      respectively). CONCLUSIONS: The extracardiac conduit is now the exclusive Fontan
      modification performed in Australia and New Zealand. Even with a higher
      proportion of high-risk cases, perioperative outcomes are excellent in the modern
      era. Hypoplastic left heart syndrome confers a higher risk of prolonged pleural
      effusion and early composite adverse outcome.

PMID- 24280719
TI  - Systematic review of the cost-effectiveness of transcatheter aortic valve
      implantation.
AB  - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has emerged as an
      alternative treatment to aortic valve replacement (AVR) for selected patients
      with severe aortic stenosis. The present systematic review was conducted to
      analyze the cost-effectiveness of this novel technique within reimbursed
      healthcare systems. METHODS: Two reviewers used 7 electronic databases from
      January 2000 to November 2012 to identify relevant cost-effectiveness studies of
      TAVI versus AVR or medical therapy. The primary endpoints were the incremental
      cost-effectiveness ratio (ICER) and the probability of cost-effectiveness. The
      eligible studies for the present systematic review included those in which the
      cost-effectiveness data were measured or projected for TAVI and either medical
      therapy or AVR. All forms of TAVI were included, and all retrieved publications
      were limited to the English language. RESULTS: Eight studies were included for
      quantitative assessment. The ICER for TAVI compared with medical therapy for
      surgically inoperable patients ranged from US$26,302 to US$61,889 per quality
      adjusted life year gained. The probability of TAVI being cost-effective compared
      with medical therapy ranged from 0.03 to 1.00. The ICER values for TAVI compared
      with AVR for high-risk surgical candidates ranged from US$32,000 to US$975,697
      per quality-adjusted life year gained. The probability of TAVI being cost
      effective in this cohort ranged from 0.116 to 0.709. CONCLUSIONS: Depending on
      the ICER threshold selected, TAVI is potentially justified on both medical and
      economic grounds compared with medical therapy for patients deemed to be
      surgically inoperable. However, in the high-risk surgical patient cohort, the
      evidence is currently insufficient to economically justify the use of TAVI in
      preference to AVR.

PMID- 24280720
TI  - Mechanical versus bioprosthetic mitral valve replacement in patients younger than
      65 years.

PMID- 24280723
TI  - TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus
      like particle vaccines.
AB  - Virus-like particles (VLPs) are an active area of vaccine research, development
      and commercialization. Mucosal administration of VLPs provides an attractive
      avenue for delivery of vaccines with the potential to produce robust immune
      responses. Nasal and oral delivery routes are particularly intriguing due to
      differential activation of mucosa-associated lymphoid tissues. We compared both
      intranasal and oral administration of VLPs with a panel of toll-like receptor
      (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant
      activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because
      it is an effective model antigen and an active area of research and
      commercialization. To prioritize these adjuvants, VLP-specific antibody
      production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal
      pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice.
      Additional distal mucosal sites (nasal, brochoalveolar, salivary, and
      gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co
      delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad
      spectrum immune responses, systemically and at distal mucosal sites inducing VLP
      specific antibodies at all sites evaluated. In addition, these VLP-specific
      antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1),
      supporting their functionality. Oral administration and/or other TLR agonists
      tested in the panel did not consistently enhance VLP-specific immune responses.
      This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9
      agonists provides dose-sparing advantages for induction of specific and
      functional antibody responses against VLPs (i.e., non-replicating antigens) in
      the respiratory, gastrointestinal, and reproductive tract. 

PMID- 24280722
TI  - Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer
      in solid nodules.
AB  - OBJECTIVES: A single randomized trial established lobectomy as the standard of
      care for the surgical treatment of early-stage non-small cell lung cancer. Recent
      advances in imaging/staging modalities and detection of smaller tumors have once
      again rekindled interest in sublobar resection for early-stage disease. The
      objective of this study was to compare lung cancer survival in patients with non
      small cell lung cancer with a diameter of 30 mm or less with clinical stage 1
      disease who underwent lobectomy or sublobar resection. METHODS: We identified 347
      patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar
      resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule
      in the International Early Lung Cancer Action Program from 1993 to 2011.
      Differences in the distribution of the presurgical covariates between sublobar
      resection and lobectomy were assessed using unadjusted P values determined by
      logistic regression analysis. Propensity scoring was performed using the same
      covariates. Differences in the distribution of the same covariates between
      sublobar resection and lobectomy were assessed using adjusted P values determined
      by logistic regression analysis with adjustment for the propensity scores. Lung
      cancer-specific survival was determined by the Kaplan-Meier method. Cox survival
      regression analysis was used to compare sublobar resection with lobectomy,
      adjusted for the propensity scores, surgical, and pathology findings, when
      adjusted and stratified by propensity quintiles. RESULTS: Among 347 patients, 10
      year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294
      patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86%
      (confidence interval, 75-96) (P = .86). Cox survival analysis showed no
      significant difference between sublobar resection and lobectomy when adjusted for
      propensity scores or when using propensity quintiles (P = .62 and P = .79,
      respectively). For those with cancers 20 mm or less in diameter, the 10-year
      rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence
      interval, 73-96) (P = .45), and Cox survival analysis showed no significant
      difference between sublobar resection and lobectomy using either approach (P =
      .42 and P = .52, respectively). CONCLUSIONS: Sublobar resection and lobectomy
      have equivalent survival for patients with clinical stage IA non-small cell lung
      cancer in the context of computed tomography screening for lung cancer.

PMID- 24280724
TI  - Role of class III phosphatidylinositol 3-kinase during programmed nuclear death
      of Tetrahymena thermophila.
AB  - Programmed nuclear death (PND) in the ciliate protozoan Tetrahymena thermophila
      is a novel type of autophagy that occurs during conjugation, in which only the
      parental somatic macronucleus is destined to die and is then eliminated from the
      progeny cytoplasm. Other coexisting nuclei, however, such as new micro- and
      macronuclei are unaffected. PND starts with condensation in the nucleus followed
      by apoptotic DNA fragmentation, lysosomal acidification, and final resorption.
      Because of the peculiarity in the process and the absence of some ATG genes in
      this organism, the mechanism of PND has remained unclear. In this study, we focus
      on the role of class III phosphatidylinositol 3-kinase (PtdIns3K, corresponding
      to yeast Vps34) in order to identify central regulators of PND. We identified the
      sole Tetrahymena thermophila ortholog (TtVPS34) to yeast Vps34 and human PIK3C3
      (the catalytic subunit of PtdIns3K), through phylogenetic analysis, and generated
      the gene knockdown mutant for functional analysis. Loss of TtVPS34 activity
      prevents autophagosome formation on the parental macronucleus, and this nucleus
      escapes from the lysosomal pathway. In turn, DNA fragmentation and final
      resorption of the nucleus are drastically impaired. These phenotypes are similar
      to the situation in the ATG8Delta mutants of Tetrahymena, implying an
      inextricable link between TtVPS34 and TtATG8s in controlling PND as well as
      general macroautophagy. On the other hand, TtVPS34 does not appear responsible
      for the nuclear condensation and does not affect the progeny nuclear development.
      These results demonstrate that TtVPS34 is critically involved in the nuclear
      degradation events of PND in autophagosome formation rather than with an
      involvement in commitment to the death program. 

PMID- 24280727
TI  - This will be of ongoing importance for many years to come.

PMID- 24280725
TI  - In vitro assessment of IL-4- or IL-13-mediated changes in the structural
      components of keratinocytes in mice and humans.
AB  - T helper type 2 (Th2) cytokines, IL-4 and IL-13, attenuate the expression of
      genes that regulate epidermal cellular structures and the barrier function at the
      terminal stage of keratinocyte differentiation. However, whether these Th2
      cytokines act at earlier stages remains unknown. We investigated the roles of
      cytokines in expression levels of mRNAs and/or proteins in primary mouse
      keratinocytes and human keratinocyte HaCaT cells at earlier stages. We showed
      that IL-4 downregulated the expression levels of Krt1, Krt10, Dsg1, and Dsc1 via
      IL-4Ralpha- and signal transducer and activator of transcription factor 6 (STAT6)
      dependent mechanisms in differentiating mouse keratinocytes at early stages. As
      the expression levels of keratin-1 and -10 in the keratinocytes transiently
      expressing an active form of STAT6 were not downregulated, STAT6 and other IL-4
      induced molecules may synergistically regulate this expression. The restoration
      of the downregulated expression levels of Krt1 and Krt10 induced by IL-4 with the
      MEK (mitogen-activated protein kinase (MAPK)/extracellular signal-regulated
      kinase kinase) inhibitor U0126 indicated the involvement of the p44/42 MAPK
      signaling pathway in the attenuated expression. IL-13 also downregulated the
      expression of the four genes. Furthermore, IL-4 or IL-13 caused the
      downregulation of these genes in HaCaT cells and promoted the fragmentation of
      cell sheets with mechanical stress. Our results showed that IL-4 or IL-13 acted
      on differentiating keratinocytes in vitro at early stages to attenuate the gene
      expression. 

PMID- 24280726
TI  - CtBP1 overexpression in keratinocytes perturbs skin homeostasis.
AB  - Carboxyl-terminal-binding protein-1 (CtBP1) is a transcriptional corepressor with
      multiple in vitro targets, but its in vivo functions are largely unknown. We
      generated keratinocyte-specific CtBP1 transgenic mice with a keratin-5 promoter
      (K5.CtBP1) to probe the pathological roles of CtBP1. At transgene expression
      levels comparable to endogenous CtBP1 in acute skin wounds, the K5.CtBP1
      epidermis displayed hyperproliferation, loss of E-cadherin, and failed terminal
      differentiation. Known CtBP1 target genes associated with these processes, e.g.,
      p21, Brca1, and E-cadherin, were downregulated in K5.CtBP1 skin. Surprisingly,
      K5.CtBP1 pups also exhibited a hair loss phenotype. We found that expression of
      the Distal-less 3 (Dlx3), a critical regulator of hair follicle differentiation
      and cycling, was decreased in K5.CtBP1 mice. Molecular studies revealed that
      CtBP1 directly suppressed Dlx3 transcription. Consistently, K5.CtBP1 mice
      displayed abnormal hair follicles with decreased expression of Dlx3 downstream
      targets Gata3, Hoxc13, and hair keratins. In summary, this CtBP1 transgenic model
      provides in vivo evidence for certain CtBP1 functions predicted from in vitro
      studies, reveals--to our knowledge--previously unreported functions and
      transcriptional activities of CtBP1 in the context of epithelial-mesenchymal
      interplay, and suggests that CtBP1 has a pathogenic role in hair follicle
      morphogenesis and differentiation.

PMID- 24280728
TI  - Coverage and predictors of vaccination against 2012/13 seasonal influenza in
      Madrid, Spain: analysis of population-based computerized immunization registries
      and clinical records.
AB  - We aim to determine 2012-13 seasonal influenza vaccination coverage. Data were
      analyzed by age group and by coexistence of concomitant chronic conditions.
      Factors associated with vaccine uptake were identified. We also analyze a
      possible trend in vaccine uptake in post pandemic seasons. We used computerized
      immunization registries and clinical records of the entire population of the
      Autonomous Community of Madrid, Spain (6,284,128 persons) as data source. A total
      of 871,631 individuals were vaccinated (13.87%). Coverage for people aged >= 65
      years was 56.57%. Global coverage in people with a chronic condition was 15.7% in
      children and 18.69% in adults aged 15-59 years. The variables significantly
      associated with a higher likelihood of being vaccinated in the 2012-13 campaign
      for the age groups studied were higher age, being Spanish-born, higher number of
      doses of seasonal vaccine received in previous campaigns, uptake of pandemic
      vaccination, and having a chronic condition. We conclude that vaccination
      coverage in persons aged<60 years with chronic conditions is less than
      acceptable. The very low coverage among children with chronic conditions calls
      for urgent interventions. Among those aged >=60 years, uptake is higher but still
      far from optimal and seems to be descending in post-pandemic campaigns. For those
      aged >=65 years the mean percentage of decrease from the 2009/10 to the actual
      campaign has been 12%. Computerized clinical and immunization registers are
      useful tools for providing rapid and detailed information about influenza
      vaccination coverage in the population.

PMID- 24280729
TI  - Quantitative computed tomographic coronary angiography: does it predict
      functionally significant coronary stenoses?
AB  - BACKGROUND: Coronary lesions with a diameter narrowing >=50% on visual computed
      tomographic coronary angiography (CTCA) are generally considered for referral to
      invasive coronary angiography. However, similar to invasive coronary angiography,
      visual CTCA is often inaccurate in detecting functionally significant coronary
      lesions. We sought to compare the diagnostic performance of quantitative CTCA
      with visual CTCA for the detection of functionally significant coronary lesions
      using fractional flow reserve (FFR) as the reference standard. METHODS AND
      RESULTS: CTCA and FFR measurements were obtained in 99 symptomatic patients. In
      total, 144 coronary lesions detected on CTCA were visually graded for stenosis
      severity. Quantitative CTCA measurements included lesion length, minimal area
      diameter, % area stenosis, minimal lumen diameter, % diameter stenosis, and
      plaque burden [(vessel area-lumen area)/vessel area*100]. Optimal cutoff values
      of CTCA-derived parameters were determined, and their diagnostic accuracy for the
      detection of flow-limiting coronary lesions (FFR<=0.80) was compared with visual
      CTCA. FFR was <=0.80 in 54 of 144 (38%) coronary lesions. Optimal cutoff values
      to predict flow-limiting coronary lesion were 10 mm for lesion length, 1.8 mm2
      for minimal area diameter, 73% for % area stenosis, 1.5 mm for minimal lumen
      diameter, 48% for % diameter stenosis, and 76% for plaque burden. No significant
      difference in sensitivity was found between visual CTCA and quantitative CTCA
      parameters (P>0.05). The specificity of visual CTCA (42%; 95% confidence interval
      [CI], 31%-54%) was lower than that of minimal area diameter (68%; 95% CI, 57%
      77%; P=0.001), % area stenosis (76%; 95% CI, 65%-84%; P<0.001), minimal lumen
      diameter (67%; 95% CI, 55%-76%; P=0.001), % diameter stenosis (72%; 95% CI, 62%
      80%; P<0.001), and plaque burden (63%; 95% CI, 52%-73%; P=0.004). The specificity
      of lesion length was comparable with that of visual CTCA. CONCLUSIONS:
      Quantitative CTCA improves the prediction of functionally significant coronary
      lesions compared with visual CTCA assessment but remains insufficient. Functional
      assessment is still required in lesions of moderate stenosis to accurately detect
      impaired FFR.

PMID- 24280730
TI  - Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced
      arrhythmia by regulating multi-ion channels.
AB  - BACKGROUND/AIMS: Arctigenin possesses biological activities, but its underlying
      mechanisms at the cellular and ion channel levels are not completely understood.
      Therefore, the present study was designed to identify the anti-arrhythmia effect
      of arctigenin in vivo, as well as its cellular targets and mechanisms. METHODS: A
      rat arrhythmia model was established via continuous aconitine infusion, and the
      onset times of ventricular premature contraction, ventricular tachycardia and
      death were recorded. The Action Potential Duration (APD), sodium current (I(Na)),
      L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to))
      were measured and analysed using a patch-clamp recording technique in normal rat
      cardiomyocytes and myocytes of arrhythmia aconitine-induced by. RESULTS:
      Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced
      rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by
      100 uM arctigenin; the arctigenin dose also inhibited the prolongation of APD50
      and APD90 caused by 1 uM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and
      attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the
      activation process and delaying the inactivation process. Arctigenin enhanced Ito
      by facilitating the activation process and delaying the inactivation process, and
      recoverd the decreased Ito induced by aconitine. CONCLUSIONS: Arctigenin has
      displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of
      electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of
      arctigenin, leading to its antiarrhythmic effect.

PMID- 24280731
TI  - Double carbometallation of alkynes: an efficient strategy for the construction of
      polycycles.
AB  - Cyclization reactions of alkynes, especially the double carbometallation of
      alkynes, have drawn much interest from organic chemists because of their high
      efficiency in the construction of polycycles. Utilizing different nucleophiles or
      catalytic systems, various efficient strategies to access challenging skeletons
      have been extensively explored in recent years. In this review, achievements in
      this field are presented in three major parts (the syn-syn, anti-anti, and syn
      anti addition reactions of diynes or two alkyne molecules). Cyclization reactions
      of diynes initiated by nucleophiles, [2+2+n] cycloaddition, or other processes
      and reactions, involving two identical or different alkynes are described, which
      provide facile and reliable approaches to various pi systems, medium-sized rings,
      and even macrocycles. 

PMID- 24280732
TI  - A novel resting strategy for improving islet engraftment in the liver.
AB  - BACKGROUND: Several studies have revealed that posttransplant insulin treatment
      is beneficial to rest the islet grafts. However, insulin infusion per se is not
      enough to completely suppress the heavy workload arising caused by postprandial
      hyperglycemia. Therefore, the present study examined whether short-term fasting
      combined with insulin treatment could effectively prevent graft exhaustion after
      intraportal islet transplantation. METHODS: A marginal dose of syngeneic rat
      islet grafts were transplanted intraportally into the control, insulin-treated,
      and insulin+rest groups of streptozotocin-induced diabetic rats. The control
      group fed freely without insulin treatment, and the other groups were
      continuously treated with an optimal amount of insulin to maintain normoglycemia.
      In addition, the insulin+rest group fasted and received total parenteral
      nutrition during the 2 weeks after transplantation. RESULTS: The curative rate
      was significantly higher in both the insulin and insulin+rest groups than the
      control group (P<0.0001). The glucose tolerance, residual graft mass, and graft
      function were significantly ameliorated in the insulin+rest group, but not in the
      insulin group, compared to the control group (P<0.01, P=0.03, P=0.001).
      CONCLUSIONS: These data suggest that short-term fasting combined with insulin
      treatment, especially during the avascular period of the grafts, could therefore
      be a promising regimen for improving pancreatic islet engraftment in the liver.

PMID- 24280733
TI  - Questioning the myth: benefits of renin-angiotensin system blockade in kidney
      transplant recipients.

PMID- 24280735
TI  - Cyanated isoindigos for n-type and ambipolar organic thin film transistors.
AB  - A set of three core-cyanated isoindigos was synthesized by palladium-catalyzed
      cyanation of core-brominated isoindigos. With decreased LUMO level to -3.88 eV,
      the dicyanated isoindigo 5 showed ambient-stable electron mobility up to 0.044
      cm(2) V(-1) s(-1) in OTFTs with SAMs of TPA, while it exhibited ambipolar charge
      transport behaviour (0.11 cm(2) V(-1) s(-1) for electrons and 0.045 cm(2) V(-1)
      s(-1) for holes) on FOPA-modified substrates. 

PMID- 24280736
TI  - Splice site mutations in GH1 detected in previously (Genetically) undiagnosed
      families with congenital isolated growth hormone deficiency type II.
AB  - BACKGROUND: Congenital isolated growth hormone deficiency (IGHD) is a rare
      endocrine disorder that presents with severe proportionate growth failure.
      Dominant (type II) IGHD is usually caused by heterozygous mutations of GH1. The
      presentation of newly affected family members in 3 families with dominant IGHD in
      whom previous genetic testing had not demonstrated a GH1 mutation or had not been
      performed, prompted us to identify the underlying genetic cause. METHODS: GH1 was
      sequenced in 3 Caucasian families with a clinical autosomal dominant IGHD.
      RESULTS: All affected family members had severe growth hormone (GH) deficiency
      that became apparent in the first 2 years of life. GH treatment led to a marked
      increase in height SDS. So far, no other pituitary dysfunctions have become
      apparent. In the first family a novel splice site mutation in GH1 was identified
      (c.172-1G>C, IVS2-1G>C). In two other families a previously reported splice site
      mutation (c.291+1G>A, IVS3+1G>A) was found. CONCLUSION: These data show that
      several years after negative genetic testing it was now possible to make a
      genetic diagnosis in these families with a well-defined, clearly heritable,
      autosomal dominant IGHD. This underscores the importance of clinical and genetic
      follow-up in a multidisciplinary setting. It also shows that even without a
      positive family history, genetic testing should be considered if the phenotype is
      strongly suggestive for a genetic syndrome. Identification of pathogenic
      mutations, like these GH1 mutations, has important clinical implications for the
      surveillance and genetic counseling of patients and expands our knowledge on the
      genotype-phenotype correlation.

PMID- 24280737
TI  - Liver transplantation for nonresectable metastatic solid pseudopapillary
      pancreatic cancer.
AB  - BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas, also known as
      Franz tumor, Hamoudie tumor, solid-cystic-papillary epithelial neoplasm, or solid
      and cystic tumor, is a neoplasm of transitory (potential) malignancy, seen
      predominantly in young women. CASE REPORT: This report presents a female patient
      treated for a solid pseudopapillary tumor of the pancreas with hepatic
      metastases. The tumor was first diagnosed in 2006. Non-specific abdominal pain
      was the first presenting symptom. The patient underwent distal pancreatic
      resection and splenectomy in July 2006. Multifocal metastatic disease seen at
      surgery precluded radical resection. Following definitive pathology confirmation
      and the exclusion of extrahepatic metastases, the patient was referred to our
      transplant centre 18 months after pancreatic surgery, to be considered for
      orthotopic liver transplantation (OLTx). The extent of the disease was once again
      evaluated by imaging studies, followed by exploratory laparotomy. The patient
      underwent cadaveric liver transplantation in March 2008, with triple
      immunosuppression (tacrolimus, MMF, and steroids) following surgery. Presently,
      more than 5 years post-transplant, the patient has no signs of recurrent
      neoplasmatic disease. CONCLUSIONS: This is the first liver transplantation for a
      metastatic pancreatic pseudopapillary tumor in Poland, with the longest follow-up
      period described in the literature. Follow-up suggests a cautiously optimistic
      prognosis despite primary unresectability of hepatic metastases and the necessity
      for immunosuppressive therapy.

PMID- 24280738
TI  - Characterization and uncertainty evaluation of a new certified reference material
      of baicalein.
AB  - A new certified reference material (CRM) of baicalein was developed aiming to
      control the quality of baicalein and relative pharmaceuticals. Sample
      preparation, homogeneity, stability, value assignment, and uncertainty of a new
      certified reference material (CRM) of baicalein were presented in this paper.
      Characterization of the material relied on three different methods, which were
      differential scanning calorimetry (DSC), coulometric titration method (CT) and
      mass balance method. DSC and CT were used for purity determination of baicalein
      firstly. The certified value of baicalein CRM is 99.72% with an expanded
      uncertainty of 0.25% (k=2). The new CRM of baicalein can be used to validate
      analytical methods, improve the accuracy of measurement data as well as establish
      meteorological traceability of analytical results. 

PMID- 24280739
TI  - Effective determination of a pharmaceutical, sulpiride, in river water by online
      SPE-LC-MS using a molecularly imprinted polymer as a preconcentration medium.
AB  - We report an effective and a quantitative analysis method for one of
      pharmaceuticals, sulpiride, in river water by online solid phase extraction (SPE)
      connected with liquid chromatography-mass spectrometry (LC-MS) using a
      molecularly imprinted polymer as a preconcentration medium. The polymer prepared
      with a pseudo template molecule showed the selective retention ability based on
      the interval recognition of functional groups in sulpiride. Also, the imprinted
      polymer provided an effective concentration of a trace level of sulpiride in
      offline SPE with dual washing processes using water and acetonitrile, although
      another imprinted polymer prepared by an authentic method using sulpiride and
      methacrylic acid as a template and a functional monomer, respectively, showed the
      selective adsorption only in organic solvents. Furthermore, we employed the
      imprinted polymer as the preconcentration column of online SPE-LC-MS and the
      results supposed that the proposed system allowed the quantitative analysis of
      sulpiride with high sensitivity and recovery (10ng/L at 96%). Additionally, the
      determination of sulpiride in real river water without an additional spiking was
      effectively achieved by the system. 

PMID- 24280740
TI  - Quantitative proton nuclear magnetic resonance for the structural and
      quantitative analysis of atropine sulfate.
AB  - This study assessed a general method of quantitative nuclear magnetic resonance
      (qNMR) for the calibration of atropine sulfate (Active Pharmaceutical Ingredient,
      API) as reference standard. The spectra were acquired in D2O using maleic acid as
      the internal standard. Conformational behaviors of tropane ring were observed and
      studied by means of NMR and ROESY experiments at different temperature, which
      showed that the azine methyl group was at equilibrium for axial and equatorial
      conformations at room temperature. Signal delay and monitor signals of qNMR
      experimentation were optimized for quantification. The study reported here
      validated the method's linearity, range, limit of quantification, stability and
      precision. The results were consistent with the results obtained from mass
      balance approach. 

PMID- 24280741
TI  - Synthesis of a photocontrollable hydrogen sulfide donor using ketoprofenate
      photocages.
AB  - We report the design, synthesis and application of a directly photocontrollable
      hydrogen sulfide (H2S) donor, which releases H2S proportionally to the intensity
      and duration of photoirradiation. Photocontrolled H2S release from this donor was
      also demonstrated in bovine serum. This H2S donor should be suitable for use in
      various biological systems. 

PMID- 24280742
TI  - Build-up of an antimicrobial multilayer coating on a textile support based on a
      methylene blue-poly(cyclodextrin) complex.
AB  - The aim of this work was to develop an antibacterial multilayer coating activated
      with methylene blue (MB) and based on chitosan (CHT) and cyclodextrin
      polyelectrolyte (polyCD) onto a non-woven polyethylene terephthalate (PET)
      textile support. The MB-free and MB-loaded systems were built-up by applying the
      dip-coating technique, alternating soak cycles of the PET textile preliminarily
      modified with carboxylate groups in CHT and in polyCD or polyCD/MB complex
      solutions. The layer-by-layer assembly build-up was followed by optical waveguide
      lightmode spectroscopy on the one hand and by gravimetry once it was applied on
      the textile substrate on the other hand. Two chitosan grades were used, low
      molecular weight (CHT-L) and medium molecular weight (CHT-M). The influence of
      the molar ratio CD/MB in the polyCD solutions was varied and finally the system
      underwent a post reticulation with genipin. Such parameters influences were
      investigated with regard to the loading capacity in MB of the systems, the
      release kinetics profiles of MB in pure water, phosphate buffer and MEM media,
      and the degradation of the self-assembled coating in the same media. Finally,
      biological and microbiological tests were performed to demonstrate the
      cytocompatibility of the systems and their ability to display a sustained
      antibacterial effect of the device through the MB prolonged release. 

PMID- 24280743
TI  - Metformin for the treatment of hyperandrogenism in adolescents with type 1
      diabetes mellitus.
AB  - BACKGROUND: A high prevalence of hyperandrogenism has been reported in women with
      type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients
      with polycystic ovarian syndrome and in T1D patients without hyperandrogenism.
      This study sought to determine the effect of metformin on hyperandrogenism and
      ovarian function in adolescents with T1D. METHODS: We recruited 24 girls with
      T1D. The participants had hyperandrogenism and displayed suboptimal metabolic
      control. The patients were enrolled in a randomized, double-blind, placebo
      controlled trial. One group received metformin (850 mg bid) and the other group
      received a placebo. Treatment was administered for 9 months. Ovulation, steroids
      and gonadotropin levels were evaluated. RESULTS: Metformin treatment was
      associated with decreases in testosterone, free androgen index, androstenedione,
      17-OH progesterone and estradiol levels. The girls who were treated with placebo
      showed stable steroid, gonadotropin and sex hormone-binding globulin levels
      during the analysis. No differences were observed in the Ferriman-Gallwey scores,
      ovulation rates, HbA1c levels or daily insulin doses of the girls treated with
      metformin compared with the placebo group. CONCLUSION: Treating hyperandrogenic
      T1D adolescents with metformin significantly decreased the serum androgens
      compared to the placebo, but metformin therapy did not significantly affect
      clinical parameters, such as hirsutism, ovulation and metabolic control.

PMID- 24280746
TI  - Fos-icking for control of angiogenesis: increasing the longevity of peritoneal
      dialysis.
AB  - Recurring peritonitis reduces the effectiveness of peritoneal dialysis by
      increasing fibrosis and angiogenesis, ultimately causing ultrafiltration failure
      (UFF). Identifying the processes underlying UFF will provide new hope for
      patients with chronic kidney disease. Catar and colleagues demonstrate that
      transforming growth factor-beta, tumor necrosis factor-alpha, and interleukin-1
      synergize to significantly increase the production and release of vascular
      endothelial growth factor by mesothelial cells, which, if untreated, will promote
      peritoneal angiogenesis, leading to UFF. 

PMID- 24280747
TI  - TGF-beta-induced signaling circuit loops mediated by microRNAs as new therapeutic
      targets for renal fibrosis?
AB  - MicroRNAs (miRNAs) are emerging molecules in the pathogenesis of human diseases.
      Identification of miRNAs related to renal fibrosis provides clues to find new
      signaling pathways to fill the gaps between signaling molecules. Li et al. report
      another new pathway mediated by miR-433 that is induced by transforming growth
      factor-beta1 in mouse models of renal fibrosis. The signaling also makes a
      positive-feedback circuit loop, which could be translated into new therapeutic
      targets. 

PMID- 24280748
TI  - JC viruria and kidney disease in APOL1 risk genotype individuals: is this a clue
      to a gene * environment interaction?
AB  - APOL1 nephropathy occurs in a minority of genetically at-risk individuals,
      suggesting that other factors, such as other genes or environmental factors,
      contribute. Divers and colleagues report that among individuals with two APOL1
      risk alleles, those with JC viruria are less likely to manifest kidney disease
      compared with those lacking JC viruria. These data might suggest that JC virus
      infection confers protection against glomerular injury, perhaps by altering cell
      function or generating immunity against a related polyomavirus. 

PMID- 24280749
TI  - Biomarkers of acute injury: predicting the long-term outcome after
      transplantation.
AB  - Biomarkers of ischemia-reperfusion injury allow risk stratification and early
      identification of delayed graft function after kidney transplantation. Welberry
      Smith et al. describe a novel serum biomarker, aminoacylase-1, that not only is
      associated with delayed graft function but can predict the long-term outcome
      years after transplantation. 

PMID- 24280750
TI  - Alloreactive T cells and 'the persistence of memory'.
AB  - Circulating donor-reactive effector memory T cells have been associated with
      allograft injury in humans. The next step to translate this observation into
      clinical practice is the design of clinical trials aimed at individualization of
      T cell-targeted therapy. The administration of immunosuppressive therapy based on
      the presence or absence of donor-reactive effector memory T cells could influence
      clinical outcomes, but independent of such therapy, when 'the persistence of
      memory' prevails, allograft injury may occur. 

PMID- 24280751
TI  - Predicting dialysis vascular access blood flow and diameter: too much, too
      little, or just right.
AB  - Arteriovenous fistula (AVF) maturation continues to cause significant morbidity
      and mortality. Despite the magnitude of the clinical problem, however, there are
      no effective clinical or biological predictors of AVF success or failure. Caroli
      et al. describe an innovative technology that may be successful in predicting AVF
      flow and diameter using standard-of-care preoperative inputs. Pending additional
      longer-term validation, the use of this technology could help us get the right
      access into the right patient at the right time. 

PMID- 24280752
TI  - The authors reply.

PMID- 24280753
TI  - Low body mass index in nutcracker phenomenon: an underrecognized condition.

PMID- 24280754
TI  - How does hemodiafiltration improve survival?

PMID- 24280755
TI  - The author replies.

PMID- 24280757
TI  - An unusual case of therapy-resistant hypertension.

PMID- 24280758
TI  - The case: hexadactyly, blindness, obesity, and end-stage renal disease.

PMID- 24280759
TI  - Temperamental and genetic predictors of suicide attempt and self-mutilation.
AB  - BACKGROUND AND AIMS: Literature findings mainly support the notion that suicide
      attempts (SA) and self-mutilating behavior (SMB) are distinct behaviors, although
      they may share common psychopathological features. In the present paper we aimed
      to identify behavioral phenotypes in patients with SA, SMB, or both (SAM) and to
      analyze the association with candidate genes. METHODS: One hundred forty-two
      inpatients with a history of SA (n = 86), SMB (n = 22), and SAM (n = 39) were
      included in this study. Subjects were evaluated using the Tridimensional
      Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI).
      Polymorphisms within serotonin transporter (SLC6A4, HTTLPR), catechol-O-methyl
      transferase (COMT, Val158Met), and tryptophan hydroxylase (TPH, 218C>A) were also
      analyzed. RESULTS: Principal component factor analysis including the BDHI and TPQ
      produced 3 factors that could classify the 3 groups of patients with good
      sensitivity. However, only the 'pure suicidal' factor had a sufficient positive
      predictive value. This factor was characterized by high levels of persistence
      (PS) and, to a lower extent, reward dependence. The distribution of genotypes was
      not different across patient groups for all polymorphisms, but the SS genotype of
      HTTLPR was significantly associated with the 'self-mutilation' factor,
      characterized by high levels of hostile traits, novelty seeking, and harm
      avoidance. CONCLUSION: The results of the present study suggest that different
      and overlapping temperamental traits in suicidal and self-mutilating patients are
      present, although only high levels of PS could predict SA repetition. Finally,
      HTTLPR may mediate the risk for SMB through modulation of some temperamental
      traits.

PMID- 24280760
TI  - The European Trauma Course: trauma teaching goes European.

PMID- 24280761
TI  - Predictive factors for impaired renal function following nephroureterectomy in
      upper urinary tract urothelial cell carcinoma.
AB  - OBJECTIVES: Despite the uncertain value of adjuvant chemotherapy after radical
      nephroureterectomy (RNU) it is clear that impaired renal function represents a
      contraindication to its administration. The objective of this study was to
      identify possible predictive clinical factors for impaired renal function
      following RNU in patients with upper urinary tract urothelial cell carcinoma (UUT
      UCC). PATIENTS AND METHODS: A retrospective analysis was conducted of 546
      patients who underwent RNU between 1992 and 2008 at our institution. Data of
      interest for this study included estimated glomerular filtration rate (eGFR),
      age, pathological stage and preoperative hydronephrosis (HN). The predictive
      value of HN, age and pathological stage for impaired renal function after RNU was
      calculated by multivariate linear regression analysis. RESULTS: In total, 138
      patients met the criteria for inclusion, including 108 men (78%). Mean age at
      surgery was 67 +/- 10 years. There was a significant correlation (p < 0.001)
      between pre- and postoperative eGFR (decrease of 21% after NU). Preoperative HN
      was present in 51 patients (37%). On linear regression analysis, preoperative
      eGFR <=60 ml/min (p = 0.012; OR = 4.60) and HN (p = 0.027; OR = 10.34) were
      confirmed to be predictive factors for a postoperative eGFR <=60 ml/min. When
      postoperative eGFR <=45 ml/min was used as the criterion for impaired renal
      function, predictive factors proved to be preoperative eGFR <=45 ml/min (p <
      0.0001; OR = 18.53), HN (p = 0.038; OR = 0.380) and age >=70 years (p < 0.0001;
      OR = 0.169). CONCLUSIONS: Preoperative HN, older age and preoperative eGFR <60
      ml/min were proven to be predictive factors for impaired renal function after
      RNU. In these settings, neoadjuvant chemotherapy may be considered.

PMID- 24280764
TI  - Orthohalogen substituents dramatically enhance hydrogen bonding of aromatic ureas
      in solution.
AB  - The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry. Here
      we report that the introduction of chlorine or bromine atoms in the ortho
      positions to the urea unit is a simple and very efficient way to improve its
      intermolecular hydrogen bond (HB) donor character. This effect was demonstrated
      in solution both in the context of self-association of bis-ureas and hydrogen
      bonding of mono-ureas to strong HB acceptors. 

PMID- 24280763
TI  - A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust immune
      response and alleviates lung injury induced by Mycobacterium infection.
AB  - Development of effective anti-tuberculosis (TB) vaccines is one of the important
      steps to improve control of TB. Cell-mediated immune response significantly
      affects the control of M. tuberculosis infection. Thus, vaccines able to elicit
      strong cellular immune response hold special advantages against TB. In this
      study, three well-defined mycobacterial antigens (Rv3615c, Mtb10.4 [Rv0228], and
      Rv2660c) were engineered as a novel triple-antigen fusion DNA vaccine p846. The
      p846 vaccine consists of a high density of CD4(+) and CD8(+) T-cell epitopes.
      Intramuscular immunization of p846 induced robust T cells mediated immune
      response comparable to that of bacillus Calmette-Guerin (BCG) vaccination but
      more effective than that of individual antigen vaccination. After mycobacterial
      challenge, p846 immunization decreased bacterial burden at least 15-fold compared
      with individual antigen-based vaccination. Notably, the lungs of mice immunized
      with p846 exhibited fewer inflammatory cell infiltrates and less damage than
      those of control group mice. Our data demonstrate that the potential of p846
      vaccine to protect against TB and the feasibility of this design strategy for
      further TB vaccine development. 

PMID- 24280762
TI  - Signal transduction of Helicobacter pylori during interaction with host cell
      protein receptors of epithelial and immune cells.
AB  - Helicobacter pylori infections can induce pathologies ranging from chronic
      gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor
      numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease,
      peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori
      targets more than 40 known host protein receptors on epithelial or immune cells.
      A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the
      integrin alpha 5beta 1 receptor. Other targeted membrane-based receptors include
      the integrins alphavbeta 3, alphavbeta 5, and beta 2 (CD18), RPTP-alpha/beta,
      GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor,
      Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met.
      In addition, H. pylori is able to activate the intracellular receptors NOD1,
      NOD2, and NLRP3 with important roles in innate immunity. Here we review the
      interplay of various bacterial factors with host protein receptors. The
      contribution of these interactions to signal transduction and pathogenesis is
      discussed. 

PMID- 24280765
TI  - Current investigation and management of patients with syncope: results of the
      European Heart Rhythm Association survey.
AB  - The aim of this European Heart Rhythm Association (EHRA) survey was to provide an
      insight into the current practice of work-up and management of patients with
      syncope among members of the EHRA electrophysiology research network. Responses
      were received from 43 centres. The majority of respondents (74%) had no specific
      syncope unit and only 42% used a standardized assessment protocol or algorithm.
      Hospitalization rates varied from 10% to 25% (56% of the centres) to >50% (21% of
      the centres). The leading reasons for hospitalization were features suggesting
      arrhythmogenic syncope (85% of respondents), injury (80%), structural heart
      disease (73%), significant comorbidities (54%), and older age (41%). Most widely
      applied tests were electrocardiogram (ECG), echocardiography, and Holter
      monitoring followed by carotid sinus massage and neurological evaluation. An
      exercise test, tilt table test, electrophysiological study, and implantation of a
      loop recorder were performed only if there was a specific indication. The use of
      a tilt table test varied widely: 44% of respondents almost always performed it
      when neurally mediated syncope was suspected, whereas 37% did not perform it when
      there was a strong evidence for neurally mediated syncope. Physical manoeuvres
      were the most widely (93%) applied standard treatment for this syncope form. The
      results of this survey suggest that there are significant differences in the
      management of patients with syncope across Europe, specifically with respect to
      hospitalization rates and indications for tilt table testing in neurally mediated
      syncope. The majority of centres reported using ECG, echocardiography, and Holter
      monitoring as their main diagnostic tools in patients with syncope, whereas a
      smaller proportion of centres applied specific assessment algorithms. Physical
      manoeuvres were almost uniformely reported as the standard treatment for neurally
      mediated syncope. 

PMID- 24280766
TI  - Advanced interatrial block: a well-defined electrocardiographic pattern with
      clinical arrhythmological implications.

PMID- 24280767
TI  - Authors' response.

PMID- 24280769
TI  - Construct validation of an interactive digital algorithm for ostomy care.
AB  - PURPOSE: The purpose of this study was to evaluate construct validity for a
      previously face and content validated Ostomy Algorithm using digital real-life
      clinical scenarios. DESIGN: A cross-sectional, mixed-methods Web-based survey
      design study was conducted. SUBJECTS AND SETTING: Two hundred ninety-seven
      English-speaking RNs completed the study; participants practiced in both acute
      care and postacute settings, with 1 expert ostomy nurse (WOC nurse) and 2
      nonexpert nurses. METHODS: Following written consent, respondents answered
      demographic questions and completed a brief algorithm tutorial. Participants were
      then presented with 7 ostomy-related digital scenarios consisting of real-life
      photos and pertinent clinical information. Respondents used the 11 assessment
      components of the digital algorithm to choose management options. Participant
      written comments about the scenarios and the research process were collected.
      RESULTS: The mean overall percentage of correct responses was 84.23%. Mean
      percentage of correct responses for respondents with a self-reported basic ostomy
      knowledge was 87.7%; for those with a self-reported intermediate ostomy knowledge
      was 85.88% and those who were self-reported experts in ostomy care achieved
      82.77% correct response rate. Five respondents reported having no prior ostomy
      care knowledge at screening and achieved an overall 45.71% correct response rate.
      No negative comments regarding the algorithm were recorded by participants.
      CONCLUSION: The new standardized Ostomy Algorithm remains the only face, content,
      and construct validated digital clinical decision instrument currently available.
      Further research on application at the bedside while tracking patient outcomes is
      warranted.

PMID- 24280768
TI  - What do we know about benefits of H. pylori treatment in childhood?
AB  - Policy analysis shows that H. pylori test and treat strategies targeting adults
      at moderate to high risk of H. pylori-induced disease is likely to be cost
      effective for preventing digestive diseases responsible for a large global
      disease burden. Little is known, however, about health benefits to children from
      eliminating this infection. We conducted a systematic review of the evidence
      regarding health benefits to children from treatment to eliminate H. pylori
      infection.   We systematically searched Ovid MEDLINE for pertinent review
      articles published through 2012. We excluded reviews focused on treatment
      efficacy and scrutinized reference lists of selected reviews to identify
      additional eligible reviews. Fifteen reviews met specified inclusion criteria.
      Overall, they show that few reported studies investigating pediatric health
      effects of treatment for H. pylori infection were well designed with adequate
      statistical power. Thus, there is insufficient evidence for drawing conclusions
      about health benefits to children from treatment to eliminate H. pylori
      infection. 

PMID- 24280770
TI  - Predictive capacity of risk assessment scales and clinical judgment for pressure
      ulcers: a meta-analysis.
AB  - A systematic review with meta-analysis was completed to determine the capacity of
      risk assessment scales and nurses' clinical judgment to predict pressure ulcer
      (PU) development. Electronic databases were searched for prospective studies on
      the validity and predictive capacity of PUs risk assessment scales published
      between 1962 and 2010 in English, Spanish, Portuguese, Korean, German, and Greek.
      We excluded gray literature sources, integrative review articles, and
      retrospective or cross-sectional studies. The methodological quality of the
      studies was assessed according to the guidelines of the Critical Appraisal Skills
      Program. Predictive capacity was measured as relative risk (RR) with 95%
      confidence intervals. When 2 or more valid original studies were found, a meta
      analysis was conducted using a random-effect model and sensitivity analysis. We
      identified 57 studies, including 31 that included a validation study. We also
      retrieved 4 studies that tested clinical judgment as a risk prediction factor.
      Meta-analysis produced the following pooled predictive capacity indicators:
      Braden (RR = 4.26); Norton (RR = 3.69); Waterlow (RR = 2.66); Cubbin-Jackson (RR
      = 8.63); EMINA (RR = 6.17); Pressure Sore Predictor Scale (RR = 21.4); and
      clinical judgment (RR = 1.89). Pooled analysis of 11 studies found adequate risk
      prediction capacity in various clinical settings; the Braden, Norton, EMINA
      (mEntal state, Mobility, Incontinence, Nutrition, Activity), Waterlow, and Cubbin
      Jackson scales showed the highest predictive capacity. The clinical judgment of
      nurses was found to achieve inadequate predictive capacity when used alone, and
      should be used in combination with a validated scale.

PMID- 24280771
TI  - Deconstructing the photon stream from single nanocrystals: from binning to
      correlation.
AB  - Prior to the advent of single-molecule fluorescence spectroscopy, many of the
      fundamental optical properties of colloidal semiconductor nanocrystal quantum
      dots were obscured by ensemble averaging over their inherent inhomogeneities.
      Single quantum dot spectroscopy has become a leading technique for the
      unambiguous determination of the governing excitonic physics of these quantum
      confined systems. The analysis and interpretation of the timing and energies of
      photons emitted from individual nanocrystals have uncovered unexpected and
      fundamental electronic processes at the nanoscale. We review several different
      paradigms for deconstructing the photon stream from single nanocrystals, ranging
      from intensity "binning" techniques to more sophisticated methods based on single
      photon counting. In particular, we highlight photon correlation - a powerful
      developing paradigm in single-nanocrystal studies. The application of photon
      correlation techniques to single nanocrystals is changing the study of
      multiexcitonic recombination dynamics, uncovering the basic processes governing
      spectral linewidths and spectral diffusion, and enabling the extraction of single
      nanocrystal properties directly from an ensemble with high statistical
      significance. These single-molecule techniques have proven invaluable for
      understanding the physics of nanocrystals and can provide unique insight into
      other heterogeneous and dynamical systems. 

PMID- 24280773
TI  - Perceptions regarding genetic testing in populations at risk for nephropathy.
AB  - BACKGROUND: Population ancestry-based differences exist in genetic risk for many
      kidney diseases. Substantial debate remains regarding returning genetic test
      results to participants. African-Americans (AAs) and European-Americans (EAs) at
      risk for end-stage kidney disease were queried for views on the value and use of
      genetic testing in research. METHODS: A standardized survey regarding attitudes
      toward genetic testing was administered to 130 individuals (64 AA, 66 EA) with
      first-degree relatives on dialysis. Fisher's exact test was used to assess
      differences in participant attitudes between population groups. RESULTS: Mean
      (SD) age of surveyed AAs and EAs was 45.5 (12.8) and 50.5 (14.4) years,
      respectively (p = 0.04), with similar familial relationships (p = 0.22). AAs and
      EAs wished to know their test results if risk could be: (1) reduced by diet or
      exercise (100 and 98%, p = 0.99); (2) reduced by medical treatment (100 and 98%,
      p = 0.99), or (3) if no treatments were available (90 and 82%, p = 0.21). If
      informed they lacked a disease susceptibility variant, 87% of AAs and 88% of EAs
      would be extremely or pretty likely to inform family members (p = 0.84). If
      informed they had a disease susceptibility variant, 92% of AAs and 89% of EAs
      would be extremely or pretty likely to inform their family (p = 0.43).
      CONCLUSIONS: Attitudes toward obtaining and using genetic test results for
      disease in research contexts were similar in AAs and EAs at risk for end-stage
      kidney disease. A substantial majority would want information regardless of
      available treatments and would share the information with the family. These
      results have important implications for patient care, study design and the
      informed consent process.

PMID- 24280772
TI  - The TSC-mTOR pathway regulates macrophage polarization.
AB  - Macrophages are able to polarize to proinflammatory M1 or alternative M2 states
      with distinct phenotypes and physiological functions. How metabolic status
      regulates macrophage polarization remains not well understood, and here we
      examine the role of mTOR (mechanistic target of rapamycin), a central metabolic
      pathway that couples nutrient sensing to regulation of metabolic processes. Using
      a mouse model in which myeloid lineage-specific deletion of Tsc1
      (Tsc1(Delta/Delta)) leads to constitutive mTOR complex 1 (mTORC1) activation, we
      find that Tsc1(Delta/Delta) macrophages are refractory to IL-4-induced M2
      polarization, but produce increased inflammatory responses to proinflammatory
      stimuli. Moreover, mTORC1-mediated downregulation of Akt signalling critically
      contributes to defective polarization. These findings highlight a key role for
      the mTOR pathway in regulating macrophage polarization, and suggest how nutrient
      sensing and metabolic status could be 'hard-wired' to control of macrophage
      function, with broad implications for regulation of type 2 immunity, inflammation
      and allergy. 

PMID- 24280774
TI  - Pterygium recurrence, astigmatism and visual acuity following bare-sclera
      excision and conjunctival autograft with or without additional phototherapeutic
      keratectomy.
AB  - BACKGROUND: Treatment outcome in patients with pterygium following bare-sclera
      excision and conjunctival autograft (CAG) with and without phototherapeutic
      keratectomy (PTK). METHODS: Retrospective comparative analysis of 81 eyes, with
      primary and recurrent pterygia, that were analyzed for recurrence, best-corrected
      visual acuity (BCVA) and astigmatism in primary (P1 without PTK, P2 with PTK) and
      recurrent pterygia (R1 without PTK, R2 with PTK). BCVA and astigmatism were
      compared in patients with simple CAG alone (group I) or in combination with PTK
      (group II). RESULTS: Recurrence rates were 4.7, 11.6, 16.2, 23.2 and 32.5% at 3,
      6, 12, 24 and >24 months (P1), 7.1% at >24 months (P2). Recurrence rates were
      5.3, 10.5, 21.1, 21.1 and 26.3% at 3, 6, 12, 24 and >24 months (R1) and 1
      recurrence (7.7%) till month 24, and 3 (23.1%) thereafter (R2). BCVA increased
      from logarithm of the minimal angle of resolution 0.095 +/- 0.141 (mean +/- SD)
      at baseline to 0.066 +/- 0.09 (group I), and from 0.090 +/- 0.164 to 0.054 +/-
      0.124 (group II). Astigmatism decreased from -1.01 +/- 0.90 dpt at baseline to 
      0.97 +/- 1.24 dpt (group I), and from -1.19 +/- 1.55 to -0.75 +/- 0.87 dpt (group
      II). CONCLUSION: In comparison to CAG alone, additional excimer smoothing with
      PTK tends to increase BCVA and reduces recurrence rates in patients with primary
      pterygia.

PMID- 24280775
TI  - Rapid microwave-assisted sol-gel preparation of Pd-substituted LnFeO3 (Ln = Y,
      La): phase formation and catalytic activity.
AB  - We present a rapid microwave-assisted sol-gel approach to Pd-substituted LnFeO3
      (Ln = Y, La) for applications in C-C coupling reactions. These materials could be
      prepared in household microwave ovens in less than 15 minutes of reaction time
      with the final materials displaying well-defined structure and morphology. Phase
      evolution was studied using time-dependent microwave heatings and then compared
      with the results obtained from thermogravimetric analyses. Materials were
      confirmed to be phase pure by laboratory and synchrotron X-ray diffraction.
      Substituted Pd is ionic as shown by the binding energy shift from X-ray
      photoelectron spectroscopy. The short heating periods required for phase purity
      allow these materials less time for sintering as compared to conventional solid
      state preparation methods, making relatively high surface areas achievable. These
      materials have been successfully used as catalyst precursor materials for C-C
      coupling reactions in which the active species is Pd(0). Pd-substituted LnFeO3
      (Ln = Y, La) provides Pd(0) in solution which can be complexed by the ligand
      SPhos, allowing for aryl chloride coupling. 

PMID- 24280776
TI  - Obesity indices and adipokines in non-diabetic obese patients with early stages
      of chronic kidney disease.
AB  - BACKGROUND: The aim of this study was to estimate obesity parameters: waist
      circumference (WC), waist-to-hip ratio (WHR), weight-to-height ratio (WHtR),
      visceral adiposity index (VAI), body adiposity index (BAI), and serum adipokines
      (leptin, adiponectin, resistin) and their associations with estimated glomerular
      filtration rate (eGFR), serum creatinine, and microalbuminuria (MA) in patients
      with early stages of CKD and in non-CKD obese patients. MATERIAL AND METHODS: 67
      non-diabetic obese (BMI >= 30 mg/kg(2) out-clinic patients (25 males, 42
      females), aged from 36.5 to 64 years were divided into 2 groups: Group A (n=15)-
      patients with early stages of CKD (eGFR between 30 and 60 ml/min/1.73 m(2) or
      with MA >20 mg/l in morning urine sample independently from GFR) and Group B-
      patients without chronic CKD (n=52). RESULTS: In Group A compared to Group B, BAI
      and leptin were higher (42.2 +/- 7.1 vs. 37.5 +/- 7.0; p<0.05 and 51.8 +/- 26.7
      ng/mL vs. 35.3 +/- 24.9 ng/mL; p<0.05; respectively) and negative correlations
      occurred between eGFR and BAI (r=-0.709; p=0.003), leptin (r=-0.68; p=0.005), and
      resistin (r=-0.528; p<0.05). In Group B, negative correlations occurred between
      creatinine and VAI (r=-0.332; p<0.05), BAI (r=-0.619; p<0.0001), leptin (r=
      0.676; p<0.0001), and adiponectin (r=-0.423; p=0.002), and between eGFR and
      resistin (r=-0.276; p<0.05). CONCLUSIONS: BAI may be a valuable obesity parameter
      as a predictor of early stages of CKD in patients with obesity. Leptin may be an
      important pathogenic factor in obese patients with early stages of CKD. Resistin
      is associated with eGFR in obese patients, independently of CKD.

PMID- 24280778
TI  - Effects of mycophenolic Acid on the proliferation and endothelin-1 and
      interleukin-6 secretion of rat pulmonary microvascular endothelial cells.
AB  - OBJECTIVE: To investigate the effect of mycophenolic acid (MPA) on the
      proliferation of rat pulmonary microvascular endothelial cells (PMVECs) and on
      the secretion of endothelin-1 (ET-1) and interleukin-6 (IL-6) by these cells.
      METHODS: Rat PMVECs were treated with five different final concentrations of MPA
      (0, 0.1, 1, 10 and 100 MUM). The fetal bovine serum-induced proliferation of the
      PMVECs was detected using the Cell Counting Kit-8 (CCK-8). The levels of ET-1 and
      IL-6 secretion were assessed by radioimmunoassays. RESULTS: At the 24 h time
      point, the optical density (OD) values at 450 nm for the five groups showed that
      there were no significant differences between the groups treated with 0 and 0.1
      MUM MPA (P=0.388) or between the groups treated with 10 and 100 MUM MPA
      (P=0.292), but the OD values were significantly different between all other pairs
      of groups (P<0.001). At the 48 h time point, the OD values at 450 nm for the five
      groups showed that there was no significant difference between the groups treated
      with 0 and 0.1 MUM MPA (P=0.094), but the OD values were significantly different
      between all the other groups (P<0.001). At the 72 h time point, the OD values at
      450 nm for the five groups showed that there was no significant difference
      between the groups treated with the final concentrations of 0 and 0.1 MUM MPA
      (P=0.931), but the OD values were significantly different between all other pairs
      of groups (10 MUM MPA vs 100 MUM MPA: P=0.037; 0 MUM MPA vs 1 MUM MPA: P=0.006; 1
      MUM MPA vs 10 MUM MPA: P=0.005; all other comparisons: P<0.001). There were no
      significant differences in ET-1 concentration between the groups treated with 0
      and 0.1 MUM MPA (P=0.156) or the groups treated with 10 and 100 MUM MPA
      (P=0.262), but there were significant differences between all other pairs of
      groups (P<0.001). By contrast, there were no significant differences in IL-6
      concentrations between any pair of groups (P>0.05). CONCLUSIONS: MPA inhibits
      fetal bovine serum-induced rat PMVEC proliferation and ET-1 secretion in a dose
      dependent manner.

PMID- 24280780
TI  - Crosstalk between the Tor and Gcn2 pathways in response to different stresses.
AB  - Regulating growth and the cell cycle in response to environmental fluctuations is
      important for all organisms in order to maintain viability. Two major pathways
      for translational regulation are found in higher eukaryotes: the Tor signaling
      pathway and those operating through the eIF2alpha kinases. Studies from several
      organisms indicate that the two pathways are interlinked, in that Tor complex 1
      (TORC1) negatively regulates the Gcn2 kinase. Furthermore, inactivation of TORC1
      may be required for activation of Gcn2 in response to stress. Here, we use the
      model organism Schizosaccharomyces pombe to investigate this crosstalk further.
      We find that the relationship is more complex than previously thought. First, in
      response to UV irradiation and oxidative stress, Gcn2 is fully activated in the
      presence of TORC1 signaling. Second, during amino-acid starvation, activation of
      Gcn2 is dependent on Tor2 activity, and Gcn2 is required for timely inactivation
      of the Tor pathway. Our data show that the crosstalk between the two pathways
      varies with the actual stress applied. 

PMID- 24280781
TI  - Prediction of extraprostatic extension in patients with clinically organ-confined
      prostate cancer.
AB  - INTRODUCTION: Preoperative parameters for predicting extraprostatic extension
      (ECE) in clinically organ-confined prostate cancer patients are not well defined.
      Our aim was to evaluate the roles of the biopsy Gleason score, prostate-specific
      antigen (PSA)-based parameters, volume, and clinical T classification in
      prediction of ECE. MATERIALS AND METHODS: A total of 188 patients with clinically
      organ-confined prostate cancer who underwent radical prostatectomy from January
      1998 to December 2007 were included in the study. Age, prostate volume,
      preoperative total serum PSA (tPSA), free PSA, PSA density (PSAD), biopsy Gleason
      score, and clinical T classification were analyzed by univariate and multivariate
      analyses to predict ECE. RESULTS: Pathologic examination revealed 130 patients
      had organ-confined disease and 58 patients were positive for ECE. Multivariate
      logistic regression analyses showed that tPSA was an independent predictor of
      ECE. Gleason score >=8 had a trend for predicting ECE. Receiver operating
      characteristic (ROC) curves suggested that tPSA and PSAD had a similar diagnosis
      performance in the whole cohort. For patients with Gleason score of 7, PSAD was
      found to be statistically better than tPSA for predicting ECE. CONCLUSIONS: tPSA
      remains one of the most important factors for predicting ECE in prostate cancer
      patients. PSAD may be more helpful than tPSA for predicting ECE in the patients
      with Gleason score of 7.

PMID- 24280782
TI  - Facile synthesis of sandwiched Zn2GeO4-graphene oxide nanocomposite as a stable
      and high-capacity anode for lithium-ion batteries.
AB  - Traditional metal anode materials in lithium-ion batteries are plagued by
      instability upon discharge-charge cycling. We report that a unique sandwiched
      Zn2GeO4-graphene oxide nanocomposite has been synthesized on a large scale
      through a simple ion-exchange reaction, whereby Zn2GeO4 nanorods with lengths of
      600 nm and widths of 40 nm are homogeneously sandwiched into the graphene oxide
      matrix. Compared with bare Zn2GeO4 nanorods, a dramatic improvement in the
      electrochemical performance of the resulting nanocomposite has been achieved. In
      the voltage window of 0.001-3 V, the electrode of the Zn2GeO4-graphene oxide
      nanocomposite delivers a specific capacity as high as 1150 mA h g(-1) at 200 mA
      g(-1) after 100 discharge-charge cycles. Even at a high current density of 3.2 A
      g(-1), a capacity of 522 mA h g(-1) can be retained. The unusual electrochemical
      performance including highly reversible capacity and excellent rate capability
      arise from synergetic chemical coupling effects between Zn2GeO4 and graphene
      oxide.

PMID- 24280783
TI  - Association analysis of ten candidate genes in a large multinational cohort of
      small for gestational age children and children with idiopathic short stature
      (NESTEGG study).
AB  - BACKGROUND: Fetal growth failure has been associated with an increased risk of
      hypertension, cardiovascular disease and diabetes in adulthood. Exploring the
      mechanisms underlying this association should improve our understanding of these
      common adult diseases. PATIENTS AND METHODS: We investigated 225 SNPs in 10 genes
      involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B,
      MAPK1, MAPK3, PPARgamma and INS) in 1,437 children from the multinational NESTEGG
      consortium: 345 patients born small for gestational age who remained short (SGA
      S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS)
      and 394 controls. We related genotype to pre- and/or postnatal growth parameters,
      response to growth hormone (if applicable) and blood pressure. RESULTS: We found
      several clinical associations for GH1, GHR, IGF1, IGF1R, PPARgamma and MAPK1. One
      SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's
      minor allele A was significantly more prevalent among SGA and associated with
      smaller birth length (p = 0.000378) and birth weight (weaker association),
      independent of gestational age. CONCLUSION: IGF1R SNP rs4966035 is significantly
      associated with birth length, independent of gestational age. This and other
      associations suggest that polymorphisms in these genes might partly explain the
      phenotype of short children born SGA and children with ISS.

PMID- 24280784
TI  - Morphometric analysis of the cervical spinal canal on MRI.
AB  - Two useful numerical values, called the Torg ratio and the spinal canal diameter
      (SC diameter) are widely accepted as reliable morphometric determinants of spinal
      stenosis. The aims of the study were to examine morphometric determinants of the
      cervical spinal canal on MRI in both sexes and analyse them as reliable
      indicators of spinal stenosis. Measurements were made on 50 MR images (sagittal
      T2 weighted images from C3 to C7) of the cervical spine of patients from the
      Emergency Centre who had undertaken MRI of the cervical spine in addition to CT
      for various diagnostic indications. Torg ratio, used in evaluation of the spinal
      canal stenosis on plain x-ray radiographs, cannot be used as a spinal canal
      stenosis indicator due to the gender differences in the vertebral bodies' width.
      Sagittal canal diameters were more spread out in males than in females. MRI
      enables the value of the space available for the spinal cord, (SAC) to be
      determined, by subtracting the sagittal diameter of the spinal cord from the
      sagittal diameter of the spinal canal. Not gender, but individual and level
      differences in the SAC values were evident (cervical cord enlargement). SAC
      values relied more on the spinal canal than on the spinal cord, so that the
      differences in the dimensions of the spinal cord accounted for less variability
      in the SAC values. MR imaging of the cervical spine provides more accurate
      cervical canal and spinal cord measurements that could serve as morphometric
      determinants of the cervical canal stenosis.

PMID- 24280785
TI  - Ultrasonography in ocular trauma.
AB  - PURPOSE: Ultrasonography is a non-invasive, simple and effective diagnostic
      method which enables visualization and evaluation of intraocular injury degree in
      cloudy eye media. The basic aim of this investigation was to find out the
      frequency of various types of ocular injuries using ultrasonography and to make
      an analysis of their frequency in relation to gender and age. MATERIALS AND
      METHODS: This retrospective study included 182 patients hospitalized at the
      Clinic of Ophthalmology in Skopje due to mechanical eye trauma. The patients
      underwent ultrasonography on the Alcon Ultrascan Imagining System apparatus and
      Sonomed EZ Scan AB 5500+. B scan technique was used primarily, while the A scan
      had a positive and correlative role. RESULTS: Ocular trauma was more present in
      males (85.2%) compared to females (14.8%). 49.5% of the patients had open, and
      50.5% had closed globe injuries. The most represented age group in ocular
      injuries was the age ranged from 51 to 60 years. There was no significant
      difference between the type of mechanical injury and the age (Chi-Squares=5.52
      p=0.47895025). Ultrasonography showed that the most frequent pathologic result,
      both in open and closed globe injuries, was vitreous hemorrhage. CONCLUSION:
      Ultrasonography has an irreplaceable role in the clinical evaluation and
      management of ocular trauma. It showed that the most frequent finding in ocular
      trauma was vitreous haemorrhage, and the male gender was more frequently exposed
      to ocular trauma.

PMID- 24280786
TI  - The effects of time-to-surgery on mortality in elderly patients following hip
      fractures.
AB  - INTRODUCTION: Mortality occurring as a consequence of hip fracture in older
      patients is very high. Mortality is highest in the first few months after the
      injury, and this rate is kept at a high level within the first six months
      postoperatively. Current guidelines indicate that surgery should be performed
      within 48 hours of injury because early surgery is associated with lower rates of
      perioperative complications and mortality. AIM: To analyse the effects of time-to
      surgery on mortality in elderly patients with hip fracture. MATERIAL AND METHODS:
      The research was conducted at the University Traumatology Clinic in Skopje, where
      120 patients with hip fracture of age 65 and above were treated. The age span was
      55-95 years, with a mean age of 73.9+/-9.8 years. The time frame for the research
      and the follow-up of the patients was 6 months. Inclusion criteria included
      patients aged above 65 and isolated proximal femur fractures. Survival time for
      patients after six months was determined with the Kaplan-Meier product-limit
      method. Statistical significance was evaluated at level of p<0.05. RESULTS: The
      mean time from patient admission to surgical intervention was 3.07+/-1.5 days
      (range 0-6 days). Hospitalization time averaged 11+/-4.7 days. We separated our
      patient population into two groups, one consisting of patients operated in the
      first two days, the other after two days. The patient death rate in the first
      group of 25 patients operated in the first 48 hours was a total of 4 patients
      (16%) after 6 months. The second group, 95 patients operated after 48 hours,
      showed a significant rise in mortality--32 patients (33.7%). The mean survival
      time of patients operated within 48 hours is 168.8 days, while the mean survival
      time of patients operated after 48 hours from their hospital admission was 143.6
      days. CONCLUSION: Delay in surgery is associated with significant increase in
      mortality. Patients should have their operation as soon as possible after
      admission to hospital, preferably in the first 48 hours.

PMID- 24280787
TI  - Minimally invasive treatment of 56 consecutive supracondylar fractures of the
      humerus in children.
AB  - OBJECTIVE: to present our results from the minimally invasive approach in the
      treatment of 56 consecutive Gartland types II and III supracondylar fractures of
      the humerus in school-age patients. METHOD: Including criteria were isolated
      supracondylar fractures Gartland types II and III, in the period from January
      2011 to November 2011. We admitted 56 children aged four to 12 years (mean 6.9
      y.). The most common mechanism of injury was fall with the elbow extended. The
      treatment procedure consisted of four steps: 1) Classification of the injury
      according to x-ray findings; 2) Under general anaesthesia, the injured child was
      placed in a prone position; 3) Closed reduction was obtained by placing the elbow
      on a special table with the elbow flexed at 90 degrees, using gravity to help
      reposition; 4) After x-ray verification of the reduction two Sommer pins were
      inserted to stabilize the fracture. The pins were placed percutaneously through
      the medial and lateral humeral condyles respectively. After the intervention all
      elbows were immobilized in a splint cast for 3 weeks. RESULTS: All patients were
      followed up for six months. Control radiographs were performed postoperatively,
      three weeks and two months after the injury. There were no malunions or
      nonunions. We estimated the elbow function using the Mayo elbow performance
      index. The functional results were excellent and very good according to the Mayo
      score. CONCLUSION: We recommend this one-day surgical approach for the treatment
      of Gartland type II and III supracondylar fractures.

PMID- 24280788
TI  - National strategy for prevention of oral diseases in children from 0 to 14 years
      old age in the Republic of Macedonia for the period 2008-2018.
AB  - Human principles and the fundamental values are the main principles stipulated in
      the Constitution of Republic of Macedonia. The Government of the Republic of
      Macedonia, within its program objectives, implementing the laws in the country,
      the international standards and the global health care as the worlds objective of
      the Constitution of WHO. According to the information received through the health
      monitoring system, as well as the results from target and selective studies, they
      have shown that the condition of oral health, especially the condition with the
      dental caries is serious health problem of all groups. The alarm was activated by
      the state of increase of the caries incidence, showing a value of DMFT=6.88 in
      children at 12 years of age, which is considered as a high value compared to the
      WHO recommendations for oral health (DMFT=3). The experience from the developed
      countries, as well as the knowledge based on scientific and professional evidence
      in RM, prove that this desease may be successfully prevented, eliminated and
      eradicated by conduction of primary preventive measures. The program objectives
      of the National Strategy for prevention of oral deseases are shared in shorth
      term, medium term and long term objectives, which aim is eradication of the
      caries. The Strategy include a prevention of periodontal desease and orthodontic
      anomalies. The prevention of the caries will be performed by using a five
      preventive measures: 1. mechanical and chemical control of the dental plaque 2.
      Discipline of sugar take regime 3. Application of fluorides (systemic and topic)
      4. sealing fissures and cavities 5. Education and motivation for sustainnability
      of oral health. In the frame of the Strategy, we planed a dental dispensarisation
      of children through registering data in the patients file, as propose by WHO, and
      arrangement of preventive teams and professional assistance of paediatrics and
      gynecologists. The evaluation of the effects from the preventive program shall be
      performed two years from the initiation of the program implementation and the
      follow-up evaluations shall be performed every year, on the representative sample
      from the group of children at 6, 8 and 12 years of age covered with the program.
      The statistical data processing shall be presented at professional and scientific
      forums and published in the annual report of WHO.

PMID- 24280789
TI  - Understanding GME Financing.

PMID- 24280790
TI  - In reply to Grover.

PMID- 24280791
TI  - How can we get students to choose primary care careers?

PMID- 24280792
TI  - How can we get students to choose primary care careers?

PMID- 24280793
TI  - Medical student education in the EMR era requires access to the EMR.

PMID- 24280794
TI  - In reply.

PMID- 24280795
TI  - Artist's Statement: Doctor-Patient.

PMID- 24280796
TI  - Silence.

PMID- 24280797
TI  - Medicine and the arts. The Aboriginal memorial 1987-88 by Djon Mundine.
      Commentary.

PMID- 24280799
TI  - 2013 Humanism in Medicine Essay Contest: first place: antiretrovirals and small
      things.

PMID- 24280800
TI  - Ordered self-assembly of proteins for computation in mammalian cells.
AB  - A cellular logic system capable of combinatorial and sequential logic operations
      based on bacterial protein-triggered cytotoxicity was constructed. Advanced
      devices such as a keypad lock, half-adder and several basic Boolean properties
      were demonstrated on the cells. 

PMID- 24280801
TI  - Supramolecular dynamics.
AB  - Supramolecular systems are reversible and their dynamics is an inherent and
      essential property. The conceptual framework for kinetic studies of these systems
      is presented with a focus on the considerations required for experimental design.
      Selected examples for guest binding to cyclodextrins, cucurbit[n]urils, DNA,
      serum albumins and bile salt aggregates are presented that describe the type of
      information obtained from dynamic studies that are not available from
      thermodynamic investigations. 

PMID- 24280803
TI  - Diaryl-substituted norbornadienes with red-shifted absorption for molecular solar
      thermal energy storage.
AB  - Red-shifting the absorption of norbornadienes (NBDs), into the visible region,
      enables the photo-isomerization of NBDs to quadricyclanes (QCs) to be driven by
      sunlight. This is necessary in order to utilize the NBD-QC system for molecular
      solar thermal (MOST) energy storage. Reported here is a study on five diaryl
      substituted norbornadienes. The introduced aryl-groups induce a significant red
      shift of the UV/vis absorption spectrum of the norbornadienes, and device
      experiments using a solar-simulator set-up demonstrate the potential use of these
      compounds for MOST energy storage. 

PMID- 24280804
TI  - Eradication of Helicobacter pylori infection might have a positive impact on
      subpopulations with endoscopic gastro-oesophageal reflux disease.

PMID- 24280805
TI  - Answer to Professor Kountouras's letter.

PMID- 24280807
TI  - Restoring vascular function with hyperbaric oxygen treatment: recovery
      mechanisms.
AB  - Treatment with hyperbaric oxygen can be a beneficial adjuvant therapy in various
      disorders characterized by compromised tissue oxygenation and perfusion. However,
      the effects of hyperbaric oxygenation cannot be simply explained as a
      compensation of the oxygen deficit. Hyperbaric oxigenation has a much broader
      influence and has the ability to alter protein expression, modulate signaling
      pathways and affect vascular structure and function. We discuss some of the most
      important uses of hyperbaric oxigenation for clinical conditions that involve
      abnormal vascular function. We present recent studies and insights into the
      mechanisms and effects of hyperbaric oxygen in the vasculature.

PMID- 24280808
TI  - Update on hemodynamic monitoring and management in septic patients.
AB  - Severe sepsis and septic shock are associated with significant mortality.
      Effective management of this clinical syndrome includes early resuscitation with
      fluids and vasoactive drugs to maintain vital organ perfusion and oxygen
      delivery. Understanding the different approach to the management of sepsis during
      the resuscitation and ongoing management phases is essential to initiate context-
      and time-specific interventions. Manipulation of hemodynamic variables to achieve
      a balance between oxygen delivery and consumption forms the cornerstone of
      hemodynamic optimisation. Minimally invasive and completely non-invasive cardiac
      output monitors have been developed, but require validation in this specific
      cohort of patients. The trend in hemodynamic parameters is particularly important
      when any intervention to augment cardiac output is carried out (functional
      hemodynamic monitoring). Cardiac output monitors and surrogates of tissue
      oxygenation are only able to guide management, as patient outcome is determined
      by acquisition and interpretation of accurate data, and suitable management
      decisions. 

PMID- 24280809
TI  - Hemodynamics and tissue oxygenation after hemodilution with ultrahigh molecular
      weight polymerized albumin.
AB  - BACKGROUND: Compared to blood transfusion, plasma expanders (PEs) are more cost
      effective, have a longer shelf-life, and elicit a milder immune response. High
      molecular weight (MW) dextrans preserve microvascular function during extreme
      hemodilution. Dextrans, however, evokes negative hemostatic effects, including
      red blood cell (RBC) aggregation and reduce platelet adhesion, that limit their
      clinical use. Therefore, polymerization of human serum albumin (HSA) presents a
      simple strategy to increase HSA's molecular size. METHODS: This study was
      designed to test the hypothesis that polymerized HSA (PolyHSA) biophysical
      properties improves systemic and microvascular hemodynamics when used as a PE
      under anemic conditions. The study was implemented using the hamster window
      chamber model. Animals were first hemodiluted to 18% hematocrit (Hct) using 6%
      dextran 70 kDa and then to 11% Hct using either 10% PolyHSA, 10% unpolymerized
      HSA, or 6% dextran 70 kDa. Systemic and microvascular hemodynamics, including
      cardiac output (CO), mean arterial blood pressure (MAP), functional capillary
      density (FCD), microvascular perfusion, and oxygen tension were measured.
      RESULTS: Posthemodilution, PolyHSA improved MAP, CO, and oxygen delivery compared
      to HSA and dextran. Additionally, PolyHSA improved microvascular function in
      terms of blood flow and FCD. Although oxygen carrying capacity is limited at 11%
      Hct, tissue pO2 and oxygen delivery were higher for PolyHSA compared to HSA and
      dextran. CONCLUSION: PolyHSA during extreme anemia supported systemic and
      microvascular hemodynamics by increasing plasma viscosity without increasing
      vascular resistance. These findings can aid to design of studies to understand
      the role of the PE biophysical properties in clinical scenarios.

PMID- 24280810
TI  - Aerophagia increases the risk of ventilator-associated pneumonia in critically
      ill patients.
AB  - BACKGROUND: Gastric residual volume in ventilated critically ill may complicate
      gut function. Over the years studies suggested to tolerate progressively higher
      residuals. The relationship between such volumes and the development of
      ventilator-associated pneumonia (VAP) is still under debate. No reports deal with
      the relevant anecdotal finding of air in the stomach. Aim of the present study is
      to test the role of air in the development of VAPs. METHODS: Prospective
      observational trial in consecutive patients with a predicted length of ICU stay
      >3 days. The first 8 days of stay were studied. Sedation was targeted to have
      awake/cooperative patients. Early enteral nutrition was attempted. Gastric
      content was measured every 4 hours by 60 mL-syringe suction. Upper digestive
      intolerance (UDI) was defined as >2 consecutive findings of liquid >200 mL,
      aerophagia was defined as >2 consecutive findings of air >150 mL. RESULTS: Three
      hundred sixty-four patients enrolled, 43 developed VAP (11.8%). Patients were
      sedated with enteral (76% total time), intravenous (6%) or both (28%) drugs.
      Conscious sedation was achieved in 54% of the observations. 326 patients began
      enteral nutrition during the first 24 hours (1000 kcal median calorie intake).
      10% developed UDI, 15% had aerophagia. No association was found between VAP and
      UDI (P=0.78), while significant association was found between VAP and aerophagia
      (OR=2.88, P<0.01). A sensitivity analysis, excluding patients admitted with
      respiratory infection, confirmed the results. CONCLUSION: High volumes of air in
      the stomach significantly increased the risk of developing VAP, while gastric
      residual volumes were not associated with the incidence of pneumonia.

PMID- 24280811
TI  - Comparison of palonosetron with palonosetron-dexamethasone combination for
      prevention of postoperative nausea and vomiting in patients undergoing
      laparoscopic cholecystectomy.
AB  - BACKGROUND: This randomized double-blind study was designed to compare
      palonosetron with palonosetron-dexamethasone combination for prevention of post
      operative nausea and vomiting (PONV) in patients undergoing laparoscopic
      cholecystectomy. METHODS: Eighty-four adult ASA 1-2 patients were randomly
      allocated into two groups. Group P patients received 0.075 mg palonosetron and
      group PD patients received 0.075 mg palonosetron and 8 mg dexamethasone
      intravenously before induction of anesthesia. Anesthesia was induced with
      propofol and fentanyl and maintained with N2O-isoflurane in oxygen. All patients
      received port-site infiltration with bupivacaine and intravenous diclofenac for
      postoperative analgesia. Metoclopramide was used as rescue antiemetic. Patients
      were observed for the incidence of PONV and requirement of rescue antiemetic for
      48 h after surgery. RESULTS: The complete response rate (no vomiting) was
      significantly higher in group DP as compared to group P between 0-24 h (P=0.004).
      18 (42.9%) patients reported nausea and 14 (33.3%) patients had vomiting in group
      P while 6 (14.4%) patients had nausea and 5 (11.9%) patients complained of
      vomiting in group DP during 0-24 h. Two patients in group P reported nausea while
      none in group PD during 24-48 h. No patient had vomiting in either of the groups
      between 24-48 h. The requirement of rescue antiemetic was also less in group DP
      as compared to group P. Patients in group DP required less postoperative
      analgesia and were more satisfied with PONV treatment than group P patients.
      CONCLUSION: The palonosetron-dexamethasone combination was more effective as
      compared to only palonosetron for reducing PONV after laparoscopic
      cholecystectomy.

PMID- 24280812
TI  - Clinical utility of preoperative screening with STOP-Bang questionnaire in
      elective surgery.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common disease which increases the
      risk of perioperative complications. The aim of this study is to assess the
      clinical utility of preoperative screening for OSA in determining the prevalence
      of patients at high risk of OSA in a surgical population, the incidence of
      difficult airway management and the incidence of perioperative complications.
      METHODS: We conducted a multisite, prospective observational study on adult
      patients scheduled for elective surgery. All patients completed a STOP-Bang
      questionnaire as a part of their preoperative evaluation. Collected data
      included: demographic data, type of surgery, ASA class, postoperative course,
      complications within 48 hours, difficult intubation (DI) and difficult mask
      ventilation (DMV) rates. RESULTS: A total of 3452 consecutive patients were
      recruited; 2997 (87%) were identified as low OSA risk patients and 455 (13%) were
      identified as high OSA risk patients; 113 (3%) postoperative complications, 315
      (9%) cases of DMV and 375 (11%) of DI were observed. The percentage of
      postoperative complications in patients with HR-OSA was 9%, while the percentage
      of DI was 20% and the percentage of DMV was 23%. High risk for OSA and higher BMI
      (>=30 Kg m-2) were independently associated with risk for perioperative
      complications. CONCLUSION: In conclusion, this study demonstrates that the
      prevalence of high OSA risk patients in the surgical population is high. The
      increase in the rates of perioperative complications justifies the implementation
      of perioperative strategies that use the STOP-Bang as a tool for triage.

PMID- 24280813
TI  - Difference in venous-arterial carbon dioxide in septic shock.
AB  - Determining the venous-to-arterial PCO2 difference (PCO2gap) during resuscitation
      of septic shock patients might be useful when deciding when to continue
      resuscitation despite a ScvO2>70% associated with hyperlacticemia. Because
      hyperlacticemia is not a discriminatory factor in defining the cause of that
      stress, a PCO2gap>6 mmHg could be used to identify global tissue hypoperfusion.
      Monitoring the "Gap" could be a useful complementary tool after optimization of
      O2-derived parameters was achieved to evaluate the adequacy of blood flow to
      global metabolic demand. In this regard it can help to titrate inotropes in order
      to adapt O2 delivery to CO2 production, or to choose between haemoglobin
      correction or fluid/inotrope infusion in patients with a too low ScvO2 related to
      metabolic demand. 

PMID- 24280814
TI  - Low plasma fibrinogen levels and blood product transfusion in liver
      transplantation.
AB  - BACKGROUND: Risk of bleeding in liver transplantation is determined by surgical
      technique, preoperative hemoglobin and antifibrinolitic therapy. We hypothesized
      that keeping these confounders factors identical, preoperative plasma fibrinogen
      level of <=2 g/L influenced on blood product requirements. METHODS: Adult
      patients underwent orthotropic liver transplantation (LT) during the period
      between January 1998 and December 2009. Cases were selected according to a
      propensity matching analysis meeting the following criteria: surgical vena cava
      preservation, tranexamic acid administration and hemoglobin range between 90 to
      120 g/L. Intraoperative management was protocolized. The main variable was the
      percentage of patients that did not require red blood cells (RBC's). RESULTS: Six
      hundred sixty-four patients with LT, 208 excluded, 266 who cannot be matched, the
      analysis was performed on 190 patients. Two cohorts: Low fibrinogen (<=2 g/L) (61
      cases) and standard fibrinogen (>2 g/L) (129 cases) were analyzed. Preoperative
      platelet count (73.5+/-52 vs. 104+/-65; 103/mm3) was different in contrast to the
      hemoglobin (104.2+/-8.6 vs. 105.6+/-8.3; g/L). Use of RBC's resulted
      significantly higher in the low fibrinogen group (median, 3 vs. 2). The number of
      patients with no blood product requirements was fewer in the low fibrinogen group
      (8 cases, 13% vs. 45 cases, 35%). The critical level of plasma fibrinogen (1 g/L)
      was reached after graft reperfusion in 7 cases (5.5%) in the standard fibrinogen
      group vs. 24 cases (39%) in the low fibrinogen group. CONCLUSION: Our data
      suggest that preoperative plasma fibrinogen level of <=2 g/L increases
      requirements for blood products during the surgical procedure of liver
      transplantation.

PMID- 24280815
TI  - Increasing the number of lungs available for transplantation.
AB  - Lung transplantation has become a standard treatment for patients with a broad
      spectrum of end stage lung diseases. Despite this success, many patients die on
      the waiting list while waiting for appropriate lungs to become available. This
      review describes the current strategies aimed at addressing this shortage of
      lungs, as well as summarizing potential future directions in the field. They
      include efforts to: 1) increase the number of organ donors by legislative action,
      and education of the public; 2) optimize the management of deceased, potential
      organ donors; 3) implement optimal criteria to determine organs suitable for
      transplantation; 4) use ex vivo reconditioning of lungs; and 5) develop
      xenotransplantation. 

PMID- 24280816
TI  - Preoperative depression and hospital length of stay in surgical patients.
AB  - BACKGROUND: The association of depression and hospital length of stay (LOS) has
      rarely been examined in surgical patients outside of cardiovascular surgery. This
      study investigates whether clinically significant preoperative depression shows
      an independent association with LOS in patients from various surgical fields
      after adjusting for age, gender and important somatic factors. METHODS: A total
      of 2624 surgical patients were included in this prospective observational study.
      Data were collected before the preoperative anesthesiological examination within
      a computer-assisted psychosocial self-assessment including screening for
      depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on
      peri- and postoperative somatic parameters were obtained from the electronic
      patient management system of the hospital six months after the preoperative
      assessment. RESULTS: LOS of patients with clinically significant depression
      (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of
      patients without depression (N.=2328; median: 4 days, interquartile range: 2-6
      days) (P<0.001). A multivariate logistic regression model with the binary
      dependent variable 'above versus below or equal to the median LOS' revealed that
      the significant association between depression and LOS persisted (OR: 1.822 [95%
      CI 1.360-2.441], P<0.001) when simultaneously including the covariates age,
      gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM
      operative severity rating. CONCLUSION: Data suggest that the association of
      depression and LOS is independent of the impact of age, gender, surgical field,
      preoperative physical health, severity of medical comorbidity and extent of
      surgical procedure. Integration of depression therapy into routine care of
      surgical patients might be an option to improve outcomes.

PMID- 24280817
TI  - Percentage hematocrit variation (PHEVAR) index as a quality indicator of patient
      blood management in cardiac surgery.
AB  - BACKGROUND: Severe hemodilution and perioperative bleeding are determinants of
      hematocrit (HCT) variations in cardiac surgery patients. These variations may be
      direct determinants of bad outcomes, and may trigger allogeneic blood product
      transfusions, which are associated with morbidity and mortality. The present
      study introduces the Percentage HEmatocrit VARiation (PHEVAR) index as a tool to
      assess the quality of patient blood management (PBM) and to possibly guide
      specific interventions. METHODS: Seven-hundred-thirteen adult cardiac surgery
      patients were included in a retrospective analysis. The PHEVAR index was assessed
      based on the HCT determination at six points in time, being represented by the
      area under the curve of the percentage HCT variation from baseline. The PHEVAR
      index was explored for association with operative mortality and other outcome
      measurements. RESULTS: The PHEVAR index was an independent predictor of operative
      mortality (odds ratio 1.015, 95% confidence interval 1.005-1.026), postoperative
      bleeding, length of mechanical ventilation; significantly higher values of PHEVAR
      were detected in patients with acute kidney injury, low cardiac output, and
      ventricular arrhythmias. Acute kidney injury was associated with a larger HCT
      variation during surgery; low cardiac output with a larger postoperative HCT
      variation; and ventricular arrhythmias with a larger preoperative HCT variation.
      CONCLUSION: The PHEVAR index reflects HCT variations during 7 days of hospital
      stay in cardiac surgery patients, is associated with mortality and morbidity, and
      may be used as a quality index for PBM.

PMID- 24280818
TI  - Epidemiology and outcome of Klebsiella pneumoniae carbapenemase-producing
      Klebsiella pneumoniae in a tertiary level Cardiac Intensive Care Unit.

PMID- 24280819
TI  - Assessment of perioperative transfusion requirement for cirrhotic patients
      undergoing elective hepatectomy.
AB  - BACKGROUND: The possibility of outlining a risk profile for perioperative blood
      transfusion of cirrhotic patients submitted to hepatic resection can help to
      rationalize transfusion policy. METHODS: Data from 323 hepatic resections,
      performed in cirrhotic patients, were reviewed. Bootstrap and a leave-one-out
      logistic regressions were applied to test the accuracy of available risk scores
      for peri-operative transfusion identified from PubMed search of the last 20
      years, to refine them, and to provide internal validation for present results.
      RESULTS: One-hundred-six patients (32.8%) required blood transfusions during
      either intra- and/or postoperative. The predictive accuracy of three identified
      risk scores was poor with the area under receiver operating characteristics
      (AUROC) curves <0.70 in all cases. Tumor diameter, hemoglobin and presence of
      coronary artery disease were confirmed, in the present cohort, as predictors of
      blood transfusion together with serum albumin and bilirubin. The leave-one-out
      logistic regression results in an AUROC of 0.80, and of 0.79 for internal
      validation, significantly higher than that of the three scores tested (P<0.001).
      A Maximal Surgical Blood Order Schedule stratification was proposed. CONCLUSION:
      The risk profile for transfusion of cirrhotic patients undergoing hepatectomy can
      be better assessed with a model that combines already known clinical factors and
      hepatic function indexes.

PMID- 24280820
TI  - Mechanical ventilation in cancer patients.
AB  - Acute respiratory failure (ARF) in cancer patients remains a frequent and severe
      complication, despite the general improved outcome over the last decade. The
      survival of cancer patients requiring ventilatory support in Intensive Care Unit
      (ICU) has dramatically improved over the last years. The diagnostic approach,
      including an invasive strategy using fiber optic bronchoscopy or a non-invasive
      strategy, must be effective to identify a diagnostic, as it is a crucial
      prognostic factor. The use of non-invasive ventilation (NIV) instead of invasive
      mechanical ventilation (IMV), has contributed to decrease mortality, but NIV has
      to be used in appropriate situations. Indeed, NIV failure (i.e., need for IMV) is
      deleterious. Classical prognostic factors are not relevant anymore. The number of
      organ failure at admission and over the first 7 ICU days governs outcomes.
      Ventilatory support can thus be included in different management contexts: full
      code management with unlimited use of life sustaining therapies, full code
      management for a limited period, no-intubation decision, or the use of palliative
      NIV. The objectives of this review article are to summarize the modified ARF
      diagnostic and therapeutic management, induced by improvements in both intensive
      care and onco-hematologic management and recent literature data. 

PMID- 24280821
TI  - Neuraxial anesthesia in patients with intracranial hypertension or cerebrospinal
      fluid shunting systems: what should the anesthetist know?
AB  - The management of patients with central nervous system disorders such as brain
      tumours, hydrocephalus, intracranial hypertension, or subarachnoid hemorrhage has
      improved in recent years resulting in increased life expectancy. Consequently,
      the prevalence of patients with increased intracranial pressure or cerebrospinal
      fluid shunting devices presenting for non-neurological procedures has increased.
      These patients commonly receive a general anesthetic, as the safety profile of
      neuraxial anesthesia in this clinical setting remains uncertain. This article
      reviews literature on neuraxial anesthesia in patients with intracranial
      hypertension or cerebrospinal fluid shunting systems. It describes current
      knowledge, exposes and weighs the real benefits and risks of this technique in
      this setting. It provides several scenarios and anesthetic options to help the
      practitioner with choosing a tailored approach in this specific population. 

PMID- 24280822
TI  - Predicting difficult mask ventilation: a crucial point of airway management in
      obese patients.

PMID- 24280823
TI  - Epidural or wound infusion?

PMID- 24280824
TI  - Non traumatic emergency surgery in nonagenarians: still a challenge.

PMID- 24280825
TI  - Fraction of mask pressure transmitted to the trachea using the Boussignac's CPAP
      facemask.

PMID- 24280826
TI  - Postoperative hemoglobin levels and its association with myocardial ischemia in
      non-cardiac surgical patients.
AB  - BACKGROUND: Low hemoglobin (Hb) levels as well as cardiac complications are
      common conditions in postoperative surgical patients and both are associated with
      poor outcome. The aim of this study was to determine the influence of
      postoperative Hb levels on myocardial ischemia in high-risk patients who
      underwent non-cardiac surgery. METHODS: In this retrospective observational
      cohort study, we evaluated 3638 consecutive patients admitted to the 24-hour
      postoperative anesthesia care unit between 2006 and 2010; 273 (8%) high-risk
      patients, defined as three or more cardiac risk factors, were selected for
      analyses. Postoperative Hb levels were divided into tertiles (low, intermediate
      and high). The endpoint of this study was myocardial ischemia which was defined
      as new electrocardiographic abnormalities and/or elevated levels of troponin-T.
      The relationship between postoperative Hb levels and myocardial ischemia was
      assessed using logistic regression analyses stratified by gender. RESULTS:
      Postoperative myocardial ischemia was present in 73 (27%) of the 273 patients.
      After adjustment for significant pre-, intra- and postoperative risk factors, 4
      independent risk factors remained for postoperative myocardial ischemia in male
      patients: age (OR 1.1; 95% CI: 1.0-1.1), a history of ischemic heart diseases (OR
      4.2; 95% CI: 1.0-17.8), renal failure (OR 5.4; 95% CI: 2.1-13.9) and
      postoperative Hb levels: intermediate tertile (10.3-11.6 g/dL) (OR 5.8; 95% CI:
      1.6-20.9) and lowest tertile (7.9-10.2 g/dL) (OR 12.9; 95% CI: 3.0-55.5).
      CONCLUSION: Postoperative Hb levels are independently associated with
      postoperative myocardial ischemia in high-risk patients undergoing non-cardiac
      surgery.

PMID- 24280827
TI  - Prevention of acute skeletal muscle wasting in critical illness.

PMID- 24280828
TI  - Transesophageal echocardiography: a new window into ventilation-perfusion
      mismatch?

PMID- 24280829
TI  - Cre recombinase induces DNA damage and tetraploidy in the absence of loxP sites.
AB  - The spatiotemporal manipulations of gene expression by the Cre recombinase (Cre)
      of bacteriophage P1 has become an essential asset to understanding mammalian
      genetics. Accumulating evidence suggests that Cre activity can, in addition to
      excising targeted loxP sites, induce cytotoxic effects, including abnormal cell
      cycle progression, genomic instability, and apoptosis, which can accelerate
      cancer progression. It is speculated that these defects are caused by Cre-induced
      DNA damage at off-target sites. Here we report the formation of tetraploid
      keratinocytes in the epidermis of keratin 5 and/or keratin 14 promoter-driven Cre
      (KRT5- and KRT14-Cre) expressing mouse skin. Biochemical analyses and flow
      cytometry demonstrated that Cre expression also induces DNA damage, genomic
      instability, and tetraploidy in HCT116 cells, and live-cell imaging revealed an
      extension of the G 2 cell cycle phase followed by defective or skipping of
      mitosis as cause for the tetraploidy. Since tetraploidy eventually leads to
      aneuploidy, a hallmark of cancer, our findings highlight the importance of
      distinguishing non-specific cytopathic effects from specific Cre/loxP-driven
      genetic manipulations when using Cre-mediated gene deletions. 

PMID- 24280831
TI  - Investigations into variations in local cationic environment in layered oxide
      series InGaO3(ZnO)m (m = 1-4).
AB  - Layered oxides of the series InGaO3(ZnO)m (m = 1-4) are interesting due to their
      structural anisotropy. Here, we report a comprehensive study of their structural
      details, focusing on the local cationic environment in bulk powder samples by
      MASNMR and EXAFS, which is hitherto not attempted. It is found that the Ga
      geometry varies gradually from pure pentacoordinated to a mixture of penta and
      tetracoordinated with increasing amounts of tetracoordination as we move across
      the series, contrary to previous reports suggesting exclusively trigonal
      bipyramidal coordination in all the compounds. A similar observation is also made
      in the case of Zn and structural evolution involving the dissolution of Ga in a
      ZnO4 tetrahedral network in a sandwich layer can be discerned, as the insulating
      ZnO layer size increases. 

PMID- 24280830
TI  - Adverse mandibular bone effects associated with kidney disease are only partially
      corrected with bisphosphonate and/or calcium treatment.
AB  - BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high
      prevalence of periodontal disease that may predispose to tooth loss and
      inflammation. The goal of this study was to test the hypotheses that a genetic
      rat model of progressive CKD would exhibit altered oral bone properties and that
      treatment with either bisphosphonates or calcium could attenuate these adverse
      changes. METHODS: At 25 weeks of age, rats were treated with zoledronate (ZOL),
      calcium gluconate, or their combination for 5 or 10 weeks. Mandible bone
      properties were assessed using micro-computed tomography to determine bone volume
      (BV/TV) and cementum-enamel junction to alveolar crest distance (CEJ-AC).
      RESULTS: Untreated CKD animals had significantly lower BV/TV at both 30 (-5%) and
      35 (-14%) weeks of age and higher CEJ-AC (+27 and 29%) compared to normal
      animals. CKD animals had a significantly higher parathyroid hormone (PTH)
      compared to normal animals, yet similar levels of C-reactive protein (CRP). ZOL
      treatment normalized BV/TV over the first 5 weeks but this benefit was lost by 10
      weeks. Calcium treatment, alone or in combination with ZOL, was effective in
      normalizing BV/TV at both time points. Neither ZOL nor calcium was able to
      correct the higher CEJ-AC caused by CKD. Calcium, but not ZOL, significantly
      reduced serum PTH, while neither treatment affected CRP. CONCLUSIONS: (i) This
      progressive animal model of CKD shows a clear mandibular skeletal phenotype
      consistent with periodontitis, (ii) the periodontitis is not associated with
      systemic inflammation as measured by CRP, and (iii) reducing PTH has positive
      effects on the mandible phenotype.

PMID- 24280833
TI  - Human complement factor H and factor H-like protein 1 are expressed in human
      retinal pigment epithelial cells.
AB  - BACKGROUND: A common haplotype in the gene for the regulator of the alternative
      pathway of complement activation factor H has been linked to individual
      predisposition to age- related macular degeneration (AMD). METHODS: In this
      study, retinal pigment epithelial (RPE) cells, i.e. immortalized ARPE-19 as well
      as primary human RPE cells, were investigated for expression of factor H and FHL
      1 by immunohistochemistry and in situ hybridization analysis. RESULTS: Factor H
      and the alternative spliced product FHL-1 are expressed in RPE cells, i.e. in
      immortalized ARPE-19 and primary human RPE cells. Factor H and FHL-1 expression
      was induced in a dose-dependent manner in ARPE-19 cells upon treatment with the
      inflammatory marker interleukin-6 (IL-6). In situ hybridization experiments
      confirmed an elevated expression rate of the factor H gene in IL-6-treated ARPE
      19 cells. AMD is characterized by complement-associated inflammatory processes in
      the retina. Thus, local synthesis of complement regulators affects the protection
      of retinal cells and may be involved in the pathogenesis at the RPE-choroid
      interface.

PMID- 24280834
TI  - Oral CPSI-2364 treatment prevents postoperative ileus in swine without impairment
      of anastomotic healing.
AB  - BACKGROUND: Postoperative ileus (POI) is an iatrogenic complication of abdominal
      surgery, mediated by a severe inflammation of the muscularis externa (ME). We
      demonstrated that orally applicated CPSI-2364 prevents POI in rodents by blockade
      of p38 MAPK pathway and abrogation of NO production in macrophages. In the
      present experimental swine study we compared the effect of orally and
      intravenously administered CPSI-2364 on POI and examined CPSI-2364 effect on
      anastomotic healing. METHODS: CPSI-2364 was administered preoperatively via oral
      or intravenous route. POI was induced by intestinal manipulation of the small
      bowel. ME specimens were examined by quantitative PCR for CCL2 chemokine gene
      expression and myeloperoxidase activity. Functional analyzes included measurement
      of ileal smooth-muscle ex vivo contractility, in vivo intestinal and colonic
      transit. Furthermore, anastomotic healing of a rectorectostomy after CPSI-2364
      treatment was assessed by perianastomotic hydroxyproline concentration, a
      histochemically evaluated healing score and anastomotic bursting pressure (ABP).
      RESULTS: CPSI-2364 abolished inflammation of the ME and improved postoperative
      smooth muscle contractility and intestinal transit independently of its
      application route. Hydroxyproline concentration and ABP measurement revealed no
      wound healing disturbances after oral or intravenous CPSI-2364 treatment whereas
      histological scoring demonstrated delayed anastomotic healing after intravenous
      treatment. CONCLUSION: CPSI-2364 effectively prevents POI in swine independently
      of its application route. Impairment of anastomotic healing could be observed
      after intravenous but not oral preoperative CPSI-2364 treatment. Subsumed, an
      oral preoperative administration of CPSI-2364 appears to be a safe and efficient
      strategy for prophylaxis of POI.

PMID- 24280835
TI  - An issue on GM and consumers.

PMID- 24280836
TI  - The Health Sciences and Technology Academy: an educational pipeline to address
      health care disparities in West Virginia.
AB  - Health and educational disparities are national issues in the United States.
      Research has shown that health care professionals from underserved backgrounds
      are more likely than others to work in underserved areas. The Association of
      American Medical Colleges' Project 3000 by 2000, to increase the number of
      underrepresented minorities in medical schools, spurred the West Virginia School
      of Medicine to start the Health Sciences and Technology Academy (HSTA) in 1994
      with the goal of supporting interested underrepresented high school students in
      pursuing college and health professions careers. The program was based on three
      beliefs: (1) if underrepresented high school students have potential and the
      desire to pursue a health professions career and are given the support, they can
      reach their goals, including obtaining a health professions degree; (2)
      underserved high school students are able to predict their own success if given
      the right resources; and (3) community engagement would be key to the program's
      success.In this Perspective, the authors describe the HSTA and its framework and
      philosophy, including the underlying theories and pedagogy from research in the
      fields of education and the behavioral/social sciences. They then offer evidence
      of the program's success, specifically for African American students, including
      graduates' high college-going rate and overwhelming intention to choose a health
      professions major. Finally, the authors describe the benefits of the HSTA's
      community partnerships, including providing mentors to students, adding
      legislative language providing tuition waivers and a budgetary line item devoted
      to the program, and securing program funding from outside sources. 

PMID- 24280837
TI  - Measuring physicians' productivity: a three-year study to evaluate a new
      remuneration system.
AB  - PURPOSE: To evaluate a new assessment tool measuring physicians' academic
      productivity and its use in a performance-based remuneration system. METHOD: The
      authors developed an assessment tool based on existing tools to measure
      productivity. Yearly, from 2008 to 2011, physicians at the University of Western
      Ontario received a score of up to three points for each of four components
      (impact, application, scholarly activity, mentorship) in each of four domains
      (clinical practice, education, research, administration). Scores were weighted by
      the percentage of time physicians spent on tasks in each domain. Year 1 scores
      were a baseline. In Years 2 and 3, scores were tied to remuneration. The authors
      compared scores and associations, accounting for age and academic rank, across
      the three years. RESULTS: The 37 participating physicians included 11 assistant,
      23 associate, and 4 full professors. The mean weighted total baseline score
      across all four domains was 7.44. Years 2 and 3 scores were highly correlated
      with Year 1 scores (r = 0.85, Years 1 and 2; r = 0.89, Years 1 and 3). Year 2
      mean weighted scores did not differ significantly from Year 1 scores. Assistant
      professors' scores improved significantly between Years 1 and 2 (+1.08, P <
      .001). Lower Year 1 scores were correlated with a greater improvement in scores
      between Years 1 and 2, and age was negatively correlated with score changes
      between Years 2 and 3. CONCLUSIONS: Although the tool may be a robust measurement
      of physicians' productivity, performance-based remuneration had no effect on
      physicians' overall performance.

PMID- 24280838
TI  - Script concordance testing: assessing residents' clinical decision-making skills
      for infant lumbar punctures.
AB  - PURPOSE: Residents must learn which infants require a lumbar puncture (LP), a
      clinical decision-making skill (CDMS) difficult to evaluate because of
      considerable practice variation. The authors created an assessment model of the
      CDMS to determine when an LP is indicated, taking practice variation into
      account. The objective was to detect whether script concordance testing (SCT)
      could measure CDMS competency among residents for performing infant LPs. METHOD:
      In 2011, using a modified Delphi technique, an expert panel of 14 attending
      physicians constructed 15 case vignettes (each with 2 to 4 SCT questions) that
      represented various infant LP scenarios. The authors distributed the vignettes to
      residents at 10 academic pediatric centers within the International Simulation in
      Pediatric Innovation, Research, and Education Network. They compared SCT scores
      among residents of different postgraduate years (PGYs), specialties, training in
      adult medicine, LP experience, and practice within an endemic Lyme disease area.
      RESULTS: Of 730 eligible residents, 102 completed 47 SCT questions. They could
      earn a maximum score of 47. Median SCT scores were significantly higher in PGY-3s
      compared with PGY-1s (difference: 3.0; 95% confidence interval [CI] 1.0-4.9;
      effect size d = 0.87). Scores also increased with increasing LP experience
      (difference: 3.3; 95% CI 1.1-5.5) and with adult medicine training (difference:
      2.9; 95% CI 0.6-5.0). Residents in Lyme-endemic areas tended to perform more LPs
      than those in nonendemic areas. CONCLUSIONS: SCT questions may be useful as an
      assessment tool to determine CDMS competency among residents for performing
      infant LPs.

PMID- 24280839
TI  - Spirituality and health: the development of a field.
AB  - Spirituality has played a role in health care for centuries, but by the early
      20th century, technological advances in diagnosis and treatment overshadowed the
      more human element of medicine. In response, a core group of medical academics
      and practitioners launched a movement to reclaim medicine's spiritual roots,
      defining spirituality broadly as a search for meaning, purpose, and
      connectedness. This commentary describes the history of the field of spirituality
      and health-its origins, its furtherance through the Medical School Objectives
      Project, and its ultimate incorporation into the curricula of over 75% of U.S.
      medical schools. The diverse efforts in developing this field within medical
      education and in national and international organizations created a need for a
      cohesive framework. The National Competencies in Spirituality and Health-created
      at a consensus conference of faculty from seven medical schools and reported here
      for the first time-answered that need.Also reported are some of the first
      applications of these competencies-competency-linked curricular projects. This
      issue of Academic Medicine features articles from three of the participating
      medical schools as well as one from an additional medical school. This commentary
      also describes another competency application: the George Washington Institute of
      Spirituality and Health-Templeton Reflection Rounds initiative, known as G-TRR,
      which has provided clerkship students with the opportunity, through reflection on
      their patient encounters, to develop their own inner resources to address the
      suffering of others. This commentary concludes with the authors' proposals for
      future directions for the field. 

PMID- 24280840
TI  - "I will never let that be ok again": student reflections on competent spiritual
      care for dying patients.
AB  - PURPOSE: To examine medical students' reflections on the spiritual care of a
      patient who has died so as to understand how students experienced this
      significant event and how they or their teams addressed patients' spiritual
      needs. METHOD: In 2010-2011, the authors gave third-year students at Loyola
      University Chicago Stritch School of Medicine an essay assignment, prompting them
      to reflect on the experience of the death of one of their patients. The authors
      analyzed the content of the essays using an iterative, multistep process. Three
      authors independently coded the essays for themes based on the competencies
      (developed by Puchalski and colleagues and reflected in the essay prompt) of
      communication, compassionate presence, patient care, and personal and
      professional development. The authors reached consensus through discussion.
      RESULTS: A salient theme in the students' writings was awareness of their
      personal and professional development. Students reported being aware that they
      were becoming desensitized to the human dimension of care, and particularly to
      dying patients and their families. Students wished to learn to contain their
      emotions to better serve their patients, and they articulated a commitment to
      addressing patient and family needs. Students identified systemic fragmentation
      of patient care as a barrier to meeting patient needs and as a facilitator of
      provider desensitization. CONCLUSIONS: Written student reflections are a rich
      source of data regarding the spiritual care of dying patients and their families.
      They provide insight into the personal and professional development of medical
      students and suggest that medical schools should support students' formation.

PMID- 24280841
TI  - The integration of the "spirituality in medicine" curriculum into the osteopathic
      communication curriculum at Kansas City University of Medicine and Biosciences.
AB  - With grant funding from the John Templeton Spirituality and Medicine Curricular
      Award to the George Washington Institute for Spirituality and Health, faculty at
      Kansas City University of Medicine and Biosciences (KCUMB) developed the
      "Spirituality in Medicine" curriculum. In developing the curriculum, faculty took
      into consideration competencies required by the Association of American Medical
      Colleges and qualitative results from surveys of medical school applicants and
      enrolled students. Strategies for curriculum delivery included lectures, panel
      discussions, role-playing, and training in the use of a spirituality assessment
      tool. A majority of the 250 students who received the training in 2010-2011 were
      able to demonstrate the following competencies: (1) being sensitive to patients'
      spiritual and cultural needs, (2) assessing patients' and their own spiritual
      needs, (3) appropriately using chaplain services for patient care, and (4)
      understanding the effects of health disparities and ethical issues on patient
      care. Challenges to implementation included a reduction in chaplain availability
      due to the economic downturn, a lack of student exposure to direct patient care
      during shadowing, too little religious diversity among chaplains, and changes in
      assignment schedules. New competencies required by the National Board of
      Osteopathic Medical Examiners overlap with and help ensure sustainability of the
      Spirituality in Medicine curriculum. KCUMB leaders have incorporated the use of
      the spirituality assessment tool into other parts of the curriculum and into
      service experiences, and they have introduced a new elective in palliative care.
      Synergistic efforts by faculty leaders for this initiative were critical to the
      implementation of this curriculum. 

PMID- 24280842
TI  - Assessing third-year medical students' ability to address a patient's spiritual
      distress using an OSCE case.
AB  - PURPOSE: To inform curricular development by assessing the ability of third-year
      medical students to address a patient's spiritual distress during an acute
      medical crisis in the context of an objective structured clinical examination
      (OSCE) case. METHOD: During March and April 2010, 170 third-year medical students
      completed an eight-station videotaped OSCE at Albert Einstein College of Medicine
      of Yeshiva University. One of the standardized patients (SPs) was a 65-year-old
      man with acute chest pain who mentioned his religious affiliation and fear of
      dying. If prompted, he revealed his desire to speak with a chaplain. The SP
      assessed students' history taking, physical examination, and communication
      skills. In a postencounter written exercise, students reported their responses to
      the patient's distress via four open-ended questions. Analysis of the
      postencounter notes was conducted by three coders for emergent themes. Clinical
      skills performance was compared between students who reported making chaplain
      referral and those who did not. RESULTS: A total of 108 students (64%) reported
      making a chaplain referral; 4 (2%) directly addressed the patient's
      religious/spiritual beliefs. Students' clinical performance scores showed no
      significant association with whether they made a chaplain referral. CONCLUSIONS:
      Findings suggest that the majority of medical students without robust training in
      addressing patients' spiritual needs can make a chaplain referral when faced with
      a patient in spiritual crisis. Yet, few students explicitly engaged the patient
      in a discussion of his beliefs. Thus, future studies are needed to develop more
      precise assessment measures that can inform development in spirituality and
      medicine curricula.

PMID- 24280843
TI  - Teaching medical error disclosure to residents using patient-centered simulation
      training.
AB  - PURPOSE: To determine whether a standardized patient encounter and self-guided
      tutorial would improve first-year residents' self-efficacy for disclosing medical
      errors. METHOD: In 2011, 55 first-year residents participated in a simulation in
      which they disclosed an error to a standardized patient playing the part of a
      family member. Residents completed the simulation twice, four weeks apart, and
      completed presession knowledge and self-efficacy (based on the Accreditation
      Council for Graduate Medical Education [ACGME] core competencies) assessments and
      repeated the self-efficacy assessment after the sessions. Residents reviewed the
      videos of their encounters either alone (self-debrief) or with a faculty observer
      (faculty debrief). Between sessions, they completed a self-paced learning
      tutorial. Two external faculty also rated the residents' performances using
      videos of the encounters. RESULTS: Residents' self-efficacy significantly
      increased from a Session 1 pretest mean (standard deviation) score of 119.6
      (26.6) to a Session 2 posttest score of 150.3 (24.9) for all ACGME competencies
      (P < .001, Cohen's d = 1.19). The external reviewers' ratings provided
      additional, objective support for residents' improvement on questions assessing
      ACGME competencies (P = .001). Comparisons of the self-efficacy of residents in
      the self-debrief versus faculty debrief groups yielded no significant differences
      on any ACGME competencies. CONCLUSIONS: Timely, explicit, and empathetic
      disclosure of medical errors to patients and family is essential to maintaining
      trust and is an important part of patient-centered medical care. This
      intervention easily could be replicated in other settings and is applicable to
      many members of the health care team, not just to residents.

PMID- 24280844
TI  - Development and verification of a taxonomy of assessment metrics for surgical
      technical skills.
AB  - PURPOSE: To create and empirically verify a taxonomy of metrics for assessing
      surgical technical skills, and to determine which types of metrics, skills,
      settings, learners, models, and instruments were most commonly reported in the
      technical skills assessment literature. METHOD: In 2011-2012, the authors used a
      rational analysis of existing and emerging metrics to create the taxonomy, and
      used PubMed to conduct a systematic literature review (2001-2011) to test the
      taxonomy's comprehensiveness and verifiability. Using 202 articles identified
      from the review, the authors classified metrics according to the taxonomy and
      coded data concerning their context and use. Frequencies (counts, percentages)
      were calculated for all variables. RESULTS: The taxonomy contained 12 objective
      and 4 subjective categories. Of 567 metrics identified in the literature, 520
      (92%) were classified using the new taxonomy. Process metrics outnumbered outcome
      metrics by 8:1. The most frequent metrics were "time," "manual techniques"
      (objective and subjective), "errors," and "procedural steps." Only one new
      metric, "learning curve," emerged. Assessments of basic motor skills and skills
      germane to laparoscopic surgery dominated the literature. Novices, beginners, and
      intermediate learners were the most frequent subjects, and box trainers and
      virtual reality simulators were the most frequent models used for assessing
      performance. CONCLUSIONS: Metrics convey what is valued in human performance.
      This taxonomy provides a common nomenclature. It may help educators and
      researchers in procedurally oriented disciplines to use metrics more precisely
      and consistently. Future assessments should focus more on bedside tasks and open
      surgical procedures and should include more outcome metrics.

PMID- 24280845
TI  - Educational outcomes for students enrolled in MD-PhD programs at medical school
      matriculation, 1995-2000: a national cohort study.
AB  - PURPOSE: To describe educational outcomes for a national cohort of students who
      enrolled in MD-PhD programs at medical school matriculation (MD-PhD
      matriculants). METHOD: The authors used multivariate logistic regression to
      identify factors independently associated with overall MD-PhD program attrition
      (MD-only graduation or medical school withdrawal/dismissal) compared with MD-PhD
      program graduation among the 1995-2000 national cohort of MD-PhD matriculants at
      medical schools with and without Medical Scientist Training Program (MSTP)
      support. RESULTS: Of 2,582 MD-PhD matriculants, 1,885 (73.0%) were MD-PhD
      graduates, 597 (23.1%) were MD-only graduates, and 100 (3.9%) withdrew/were
      dismissed from medical school by July 2011. MD-PhD matriculants at non-MSTP
      funded schools (adjusted odds ratio [AOR], 1.96; 95% confidence interval [CI],
      1.60-2.41) and who had lower Medical College Admission Test scores (< 31 versus
      >= 36: AOR, 1.60; 95% CI, 1.20-2.14; 31-33 versus >= 36: AOR, 1.31; 95% CI, 1.01
      1.70) were more likely to leave the MD-PhD program; matriculants who reported
      greater planned career involvement in research (AOR, 0.65; 95% CI, 0.51-0.84) and
      matriculated more recently (AOR, 0.90; 95% CI, 0.85-0.96) were less likely to
      leave the MD-PhD program. Gender, race/ethnicity, and premedical debt were not
      independently associated with overall MD-PhD program attrition. CONCLUSIONS: Most
      MD-PhD matriculants completed the MD-PhD program; most of those who left were MD
      only graduates. Findings regarding variables associated with attrition can inform
      efforts to recruit and support students through successful completion of MD-PhD
      program requirements.

PMID- 24280846
TI  - Why do doctors make mistakes? A study of the role of salient distracting clinical
      features.
AB  - PURPOSE: Diagnostic errors have been attributed to faulty reasoning and cognitive
      biases, but minimizing errors requires understanding the mechanisms underlying
      biases. The authors investigated whether salient distracting features (SDFs)-case
      findings that tend to grab physicians' attention because they are strongly
      associated with a particular disease, but are indeed unrelated to the problem
      misdirect diagnostic reasoning, causing errors. METHOD: In a 2012 study conducted
      at Erasmus Medical Centre, Rotterdam, 72 internal medicine residents diagnosed 12
      clinical cases (6 simple, 6 complex) in three different formats: without a SDF,
      with a SDF in the beginning, and with a SDF at the end. In a within-subjects
      design, each participant solved 2 simple cases and 2 complex cases in each
      format. Proportions of correct diagnoses in each case type were compared by
      performing repeated-measures analysis of variance (ANOVA). RESULTS: There was a
      significant main effect of SDFs and a significant interaction effect between SDFs
      and case complexity. The presence of SDFs in the beginning of complex cases
      caused errors decreasing the proportion of correct diagnoses in comparison both
      with cases without SDFs (0.18, 95% CI, 0.13-0.23 versus 0.43, 95% CI, 0.35-0.51;
      P < .001) or with SDFs at the end (0.18, 95% CI, 0.13-0.23 versus 0.36, 95% CI,
      0.29-0.43; P < .001). SDFs did not affect performance when presented near the end
      of cases. CONCLUSIONS: SDFs early in a case are apparently an important source of
      diagnostic errors. Physicians should be aware of the need to overcome their
      influence.

PMID- 24280848
TI  - Primary care residency choice and participation in an extracurricular
      longitudinal medical school program to promote practice with medically
      underserved populations.
AB  - PURPOSE: In 2006, the University of Washington School of Medicine (UWSOM)
      launched the Underserved Pathway (UP), an extracurricular longitudinal experience
      supporting student interest in caring for underserved populations. This study
      examined the association between UP participation and residency choice. METHOD:
      The study population was 663 UWSOM graduates who matched to a residency from 2008
      to 2011; 69 were UP participants. Outcomes included matching to primary care
      residencies (family medicine, internal medicine, pediatrics, or medicine
      pediatrics). The authors calculated graduate rates and odds of UP participants
      versus nonparticipants matching to primary care residencies overall and to
      residencies in individual primary care specialties. This analysis included all
      graduates and 513 graduates who had dual interest in primary care and underserved
      care at matriculation. Of 336 graduates matching to primary care, the authors
      calculated rates of entering the individual specialties with respect to UP
      participation. RESULTS: UP participants matched at significantly higher rates
      than nonparticipants to primary care (72.5% versus 48.1%, adjusted odds ratio
      [OR] 2.2) and family medicine residencies (33.3% versus 15.0%, adjusted OR 2.9).
      Of graduates with dual matriculation interest in primary care and underserved
      care, 73.4% of participants versus 53.5% of nonparticipants matched to primary
      care (adjusted OR 1.9), and 31.2% of participants versus 18.0% of nonparticipants
      matched to family medicine (adjusted OR 2.1). Of primary care matched graduates,
      46.0% of participants versus 31.1% of nonparticipants entered family medicine.
      CONCLUSIONS: Supporting student interest in underserved careers is associated
      with higher rates of graduates entering primary care residencies, specifically
      family medicine.

PMID- 24280847
TI  - Forceps delivery volumes in teaching and nonteaching hospitals: are volumes
      sufficient for physicians to acquire and maintain competence?
AB  - PURPOSE: The decline in the use of forceps in operative deliveries over the last
      two decades raises questions about teaching hospitals' ability to provide
      trainees with adequate experience in the use of forceps. The authors examined (1)
      the number of operative deliveries performed in teaching and nonteaching
      hospitals, and (2) whether teaching hospitals performed a sufficient number of
      forceps deliveries for physicians to acquire and maintain competence. METHOD: The
      authors used State Inpatient Data from nine states to identify all women
      hospitalized for childbirth in 2008. They divided hospitals into three
      categories: major teaching, minor teaching, and nonteaching. They calculated
      delivery volumes (total operative, cesarean, vacuum, forceps, two or more
      methods) for each hospital and compared data across hospital categories. RESULTS:
      The sample included 1,344,305 childbirths in 835 hospitals. The mean cesarean
      volumes for major teaching, minor teaching, and nonteaching hospitals were 969.8,
      757.8, and 406.9. The mean vacuum volumes were 301.0, 304.2, and 190.4, and the
      mean forceps volumes were 25.2, 15.3, and 8.9. In 2008, 31 hospitals (3.7% of all
      hospitals) performed no vacuum extractions, and 320 (38.3%) performed no forceps
      deliveries. In 2008, 13 (23%) major teaching and 44 (44%) minor teaching
      hospitals performed five or fewer forceps deliveries. CONCLUSIONS: Low forceps
      delivery volumes may preclude many trainees from acquiring adequate experience
      and proficiency. These findings highlighted broader challenges, faced by many
      specialties, in ensuring that trainees and practicing physicians acquire and
      maintain competence in infrequently performed, highly technical procedures.

PMID- 24280849
TI  - Comparing teaching versus nonteaching hospitals: the association of patient
      characteristics with teaching intensity for three common medical conditions.
AB  - PURPOSE: To quantify the role of teaching hospitals in direct patient care, the
      authors compared characteristics of patients served by hospitals of varying
      teaching intensity. METHOD: The authors studied Medicare beneficiaries >= 66
      years old, hospitalized in 2009-2010 for acute myocardial infarction, heart
      failure, or pneumonia. They categorized hospitals as nonteaching, teaching, or
      Council of Teaching Hospitals and Health Systems (COTH) members and performed
      secondary analyses using intern and resident-to-bed ratios. The authors used
      descriptive statistics, adjusted odds ratios, and linear propensity scores to
      compare patient characteristics among teaching intensity levels. They
      supplemented Medicare mortality model variables with race, transfer status, and
      distance traveled. RESULTS: Adjusted for comorbidities, black patients had 2.44
      (95% confidence interval [CI] 2.36-2.52), 2.56 (95% CI 2.51-2.60), and 2.58 (95%
      CI 2.51-2.65) times the odds of COTH hospital admission compared with white
      patients for acute myocardial infarction, heart failure, and pneumonia,
      respectively. For patients transferred from another hospital's inpatient setting,
      the corresponding adjusted odds ratios of COTH hospital admission were 3.99 (95%
      CI 3.85-4.13), 4.60 (95% CI 4.34-4.88), and 4.62 (95% CI 4.16-5.12). Using
      national data, distributions of propensity scores (probability of admission to a
      COTH hospital) varied markedly among teaching intensity levels. Data from
      Massachusetts and California illustrated between-state heterogeneity in COTH
      utilization. CONCLUSIONS: Major teaching hospitals are significantly more likely
      to provide care for minorities and patients requiring transfer from other
      institutions for advanced care.Both are essential to an equitable and high
      quality regional health care system.

PMID- 24280850
TI  - Am I right when I am sure? Data consistency influences the relationship between
      diagnostic accuracy and certainty.
AB  - PURPOSE: When gauging diagnostic accuracy cognitive biases may lead to inaccurate
      estimates of certainty, predisposing clinicians to diagnostic errors. This study
      explored the relationship between diagnostic accuracy and measures of certainty
      for diagnoses based on consistent or inconsistent information. METHOD: The
      authors analyzed three experiments among 180 to 190 postgraduate trainees
      performing cardiac physical diagnoses using a simulator from 2010 to 2012. Each
      asked participants to assess diagnostic certainty. One experiment used a seven
      point certainty scale and provided only simulated physical findings. Two assessed
      certainty continuously (probability 1%-100%) and included cases with inconsistent
      clinical information in addition to simulated physical findings. Relationships
      between certainty and accuracy were explored through descriptive statistics and
      nonparametric tests. RESULTS: Measures of certainty ranged widely (between 2 and
      7, and 5%-100%). Relationships between accuracy and certainty varied depending on
      information consistency. In experiments providing only simulated findings, or
      consistent clinical data, diagnostic accuracy was associated with higher
      certainty (median 90% versus 75%, and 5/7 versus 4/7, both P < .001). Studies
      providing inconsistent data generated similar certainty among participants
      regardless of accuracy (median 75% versus 75%, P = .36; and 80% versus 85%, P =
      .60). CONCLUSIONS: Diagnostic accuracy was moderately associated with higher
      certainty only when clinical data were consistent. This correlation disappeared
      when incon sistent data were provided, possi bly reflecting changes in reasoning
      strategies among diagnostically success ful trainees. The relationship between
      certainty and diagnostic accuracy is context dependent. Certainty is an
      unreliable surrogate for diagnostic accuracy.

PMID- 24280851
TI  - Using a teaching OSCE to prompt learners to engage with patients who talk about
      religion and/or spirituality.
AB  - PURPOSE: The objective structured clinical examination (OSCE) has only
      occasionally been used as a teaching tool. The authors describe the initial use
      of an educational innovation consisting of a teaching OSCE used as "sensitizing
      practice," followed by personal, guided, and group reflection. METHOD: Staff and
      resident physicians and one medical student (N = 28) at a community hospital's
      family medicine residency participated in the innovation during August 2012. The
      initial use of the educational innovation allowed learners to engage in a
      potentially challenging conversation with a standardized patient about religion
      and/or spirituality (R/S). The aim of the innovation was not to equip learners
      with a particular tactic to introduce or discuss R/S but, rather, to prompt
      learners to engage in mindful practice with patients who identify R/S as part of
      their biopsychosocial contexts. Written, dyadic, and group reflection added value
      to the OSCE by allowing participants to reflect on a difficult learning objective
      over time. RESULTS: Participants moved along the stages-of-change continuum when
      engaging in guided reflection compared with personal reflection. Additionally,
      all participants provided evidence of at least the preparation stage at the time
      of guided reflection. By following the OSCE's sensitizing practice with three
      periods of reflection, learners were enabled first, to recognize the need for
      readiness to address challenging communication topics (in this case, R/S) and,
      second, to reflect on practiced strategies for those conversations. CONCLUSIONS:
      The educational innovation can help learners become more aware of and skillful in
      dealing with difficult physician-patient communication topics.

PMID- 24280852
TI  - Medical students' perceptions of the physician's role in not allowing them to
      perform gynecological examinations.
AB  - PURPOSE: To determine how often medical students are not allowed to perform
      gynecological examinations during their obstetrics-gynecology clerkship, identify
      the barriers to participation related to physicians and patients, explore the
      role of the supervisory physician in not allowing medical student involvement,
      and explore differences between male and female students' experiences. METHOD:
      All medical students entering their obstetrics-gynecology clerkship at a medical
      school in the Netherlands between May and October 2011 were invited to
      participate in this study's questionnaire, which asked them to report the number
      of gynecological examinations they were allowed and not allowed to perform during
      their clerkship. Eighteen questionnaire respondents participated in three focus
      groups. RESULTS: Of the 139 medical students invited, 76 (55%) completed the
      questionnaire. Students reported a total of 2,196 instances in which they were
      not allowed to participate in the examination; 89% (n = 1,956) were related to
      the supervisory physician. Qualitative data from the focus group interviews
      showed that female supervisory physicians prioritized patients' autonomy above
      students' learning needs. Furthermore, female students were less assertive than
      male students in asking the supervisory physician for permission to participate.
      CONCLUSIONS: The physician's role in not allowing student involvement is
      substantial and results in fewer opportunities for students to perform
      gynecological examinations. For students to develop the necessary gynecological
      exam skills during their clerkship, medical educators need to improve the
      learning environment.

PMID- 24280853
TI  - Quantifying federal funding and scholarly output related to the academic
      emergency medicine consensus conferences.
AB  - PURPOSE: Every year since 2000, Academic Emergency Medicine (AEM) has presented a
      one-day consensus conference to generate a research agenda for advancement of a
      scientific topic. One of the 12 annual issues of AEM is reserved for the
      proceedings of these conferences. The purpose of this study was to measure
      academic productivity of these conferences by evaluating subsequent federal
      research funding received by authors of conference manuscripts and calculating
      citation counts of conference papers. METHOD: This was a cross-sectional study.
      In 2012, the NIH RePORTER system was searched to identify subsequent federal
      funding obtained by authors of the consensus conference issues from 2000 to 2010.
      Funded projects were coded as related or unrelated to conference topic. Citation
      counts for all conference manuscripts were quantified using Scopus and Google
      Scholar. Simple descriptive statistics were reported. RESULTS: Eight hundred
      fifty-two individual authors contributed to 280 papers published in the 11
      consensus conference issues. One hundred thirty-seven authors (16%) obtained
      funding for 318 projects. A median of 22 topic-related projects per conference
      (range 10-97) accounted for a median of $20,488,331 per conference (range
      $7,779,512 to $122,918,205). The average (+/- SD) number of citations per paper
      was 15.7 +/- 20.5 in Scopus and 23.7 +/- 32.6 in Google Scholar. CONCLUSIONS: The
      authors of consensus conference manuscripts obtained significant federal grant
      support for follow-up research related to conference themes. In addition, the
      manuscripts generated by these conferences were frequently cited. Conferences
      devoted to research agenda development appear to be an academically worthwhile
      endeavor.

PMID- 24280854
TI  - Integration of basic science and clinical medicine: the innovative approach of
      the cadaver biopsy project at the Boston University School of Medicine.
AB  - PROBLEM: Curricular integration has emerged as a consistent theme in medical
      education reform. Vertical integration of topics such as pathology offers the
      potential to bring basic science content into the clinical arena, but
      faculty/student acceptance and curricular design pose challenges for such
      integration. APPROACH: The authors describe the Cadaver Biopsy Project (CBP) at
      Boston University School of Medicine as a sustainable model of vertical
      integration. Faculty and select senior medical students obtained biopsies of
      cadavers during the first-year gross anatomy course (fall 2009) and used these to
      develop clinical cases for courses in histology (spring 2010), pathology (fall
      2010-spring 2011), and radiology (fall 2011 or spring 2012), thereby linking
      students' first experiences in basic sciences with other basic science courses
      and later clinical courses. Project goals included engaging medical stu dents in
      applying basic science princi ples in all aspects of patient care as they acquire
      skills. The educational intervention used a patient (cadaver)-centered approach
      and small-group, collaborative, case-based learning. OUTCOMES: Through this
      project, the authors involved clinical and basic science faculty-plus senior
      medical students-in a collaborative project to design and implement an integrated
      curriculum through which students revisited, at several different points, the
      microscopic structure and pathophysiology of common diseases. NEXT STEPS:
      Developing appropriate, measurable out comes for medical education initiatives,
      including the CBP, is challenging. Accumu lation of qualitative feedback from
      surveys will guide continuous improvement of the CBP. Documenting longer-term
      impact of the curricular innovation on test scores and other competency-based
      outcomes is an ultimate goal.

PMID- 24280855
TI  - How can students' diagnostic competence benefit most from practice with clinical
      cases? The effects of structured reflection on future diagnosis of the same and
      novel diseases.
AB  - PURPOSE: To develop diagnostic competence, students should practice with many
      examples of clinical problems to build rich mental representations of diseases.
      How to enhance learning from practice remains unknown. This study investigated
      the effects of reflection on cases compared with generating a single or
      differential diagnosis. METHOD: In 2012, during the learning phase, 110 fourth
      year medical students diagnosed four cases of two criterion diseases under three
      different experimental conditions: structured reflection, single-diagnosis, or
      differential-diagnosis. One week later, they diagnosed two novel exemplars of
      each criterion disease and four cases of new diseases that were not among the
      cases of the learning phase but were plausible alternative diagnoses. RESULTS:
      Diagnostic performance did not differ among the groups in the learning phase. One
      week later, the reflection group obtained higher mean diagnostic accuracy scores
      (range: 0-1) than the other groups when diagnosing new exemplars of criterion
      diseases (reflection: 0.67; single-diagnosis: 0.36, P < .001; differential
      diagnosis: 0.51, P = .014) and cases of new diseases (reflection: 0.44; single
      diagnosis: 0.32, P = .010; differential-diagnosis: 0.33, P = .015). No difference
      was found between the single-diagnosis and the differential-diagnosis conditions.
      CONCLUSIONS: Structured reflection while practicing with cases enhanced learning
      of diagnosis both of the diseases practiced and of their alternative diagnoses,
      suggesting that reflection not only enriched mental representations of diseases
      practiced relative to more conventional approaches to clinical learning but also
      influenced the representations of adjacent but different diseases. Structured
      reflection seems a useful addition to the existing clinical teaching methods.

PMID- 24280856
TI  - Test-enhanced web-based learning: optimizing the number of questions (a
      randomized crossover trial).
AB  - PURPOSE: Questions enhance learning in Web-based courses, but preliminary
      evidence suggests that too many questions may interfere with learning. The
      authors sought to determine how varying the number of self-assessment questions
      affects knowledge outcomes in a Web-based course. METHOD: The authors conducted a
      randomized crossover trial in one internal medicine and one family medicine
      residency program between January 2009 and July 2010. Eight Web-based modules on
      ambulatory medicine topics were developed, with varying numbers of self
      assessment questions (0, 1, 5, 10, or 15). Participants completed modules in four
      different formats each year, with sequence randomly assigned. Participants
      completed a pretest for half their modules. Outcomes included knowledge,
      completion time, and module ratings. RESULTS: One hundred eighty residents
      provided data. The mean (standard error) percent correct knowledge score was 53.2
      (0.8) for pretests and 73.7 (0.5) for posttests. In repeated-measures analysis
      pooling all data, mean posttest knowledge scores were highest for the 10- and 15
      question formats (75.7 [1.1] and 74.4 [1.0], respectively) and lower for 0-, 1-,
      and 5-question formats (73.1 [1.3], 72.9 [1.0], and 72.8 [1.5], respectively); P
      = .04 for differences across all modules. Modules with more questions generally
      took longer to complete and were rated higher, although differences were small.
      Residents most often identified 10 questions as ideal. Posttest knowledge scores
      were higher for modules that included a pretest (75.4 [0.9] versus 72.2 [0.9]; P
      = .0002). CONCLUSIONS: Increasing the number of self-assessment questions
      improves learning until a plateau beyond which additional questions do not add
      value.

PMID- 24280857
TI  - Connectedness, sense of community, and academic satisfaction in a novel community
      campus medical education model.
AB  - PURPOSE: Developing a sense of community and establishing connectivity are
      important in enhancing learners' success and preventing their sense of isolation.
      The A.T. Still University School of Osteopathic Medicine in Arizona (SOMA) has
      implemented a novel approach to medical education in which, beginning in the
      second year, students are geographically dispersed to 11 community campuses
      associated with community health centers around the United States, at both inner
      city and rural locations. This study assessed students' sense of community,
      academic satisfaction, and level of connectedness in their first through fourth
      years of medical school at SOMA. METHOD: The Rovai Classroom Community Scale and
      open-ended questions were administered via an online survey instrument to 412
      students enrolled at SOMA for the 2011-2012 academic year. Participation was
      voluntary, and all results were anonymous. Data were analyzed using one-way ANOVA
      to compare results between classes. RESULTS: Comparisons revealed an increasing
      degree of isolation and a decreasing sense of community and academic satisfaction
      progressing from the first through fourth years of medical school. Students
      suggested possible solutions that may be applied to medical schools and other
      graduate schools to improve the level of connectedness for students who are
      learning at a distance. CONCLUSIONS: Connectivity, sense of community, and
      academic satisfaction may decrease for students in undergraduate medical
      education participating in a combination of distance learning and intermittent in
      person activities. Interventions have the potential to improve these parameters.
      Long-term follow-up of students' satisfaction is suggested.

PMID- 24280858
TI  - Forging successful academic-community partnerships with community health centers:
      the California statewide Area Health Education Center (AHEC) experience.
AB  - Increased access to insurance under the Affordable Care Act will increase demands
      for clinical services in community health centers (CHCs). CHCs also have an
      increasingly important educational role to train clinicians who will remain to
      practice in community clinics. CHCs and Area Health Education Centers (AHECs) are
      logical partners to prepare the health workforce for the future. Both are
      sponsored by the Health Resources and Services Administration, and they share a
      mission to improve quality of care in medically underserved communities. AHECs
      emphasize the educational side of the mission, and CHCs the service side.
      Building stronger partnerships between them can facilitate a balance between
      education and service needs.From 2004 to 2011, the California Statewide AHEC
      program and its 12 community AHECs (centers) reorganized to align training with
      CHC workforce priorities. Eight centers merged into CHC consortia; others
      established close partnerships with CHCs in their respective regions. The authors
      discuss issues considered and approaches taken to make these changes.
      Collaborative innovative processes with program leadership, staff, and center
      directors revised the program mission, developed common training objectives with
      an evaluation plan, and defined organizational, functional, and impact
      characteristics for successful AHECs in California. During this planning, centers
      gained confidence as educational arms for the safety net and began collaborations
      with statewide programs as well as among themselves. The AHEC reorganization and
      the processes used to develop, strengthen, and identify standards for centers
      forged the development of new partnerships and established academic-community
      trust in planning and implementing programs with CHCs. 

PMID- 24280859
TI  - How do you deliver a good obstetrician? Outcome-based evaluation of medical
      education.
AB  - The goal of medical education is the production of a workforce capable of
      improving the health and health care of patients and populations, but it is hard
      to use a goal that lofty, that broad, and that distant as a standard against
      which to judge the success of schools or training programs or particular elements
      within them. For that reason, the evaluation of medical education often focuses
      on elements of its structure and process, or on the assessment of competencies
      that could be considered intermediate outcomes. These measures are more practical
      because they are easier to collect, and they are valuable when they reflect
      activities in important positions along the pathway to clinical outcomes. But
      they are all substitutes for measuring whether educational efforts produce
      doctors who take good care of patients.The authors argue that the evaluation of
      medical education can become more closely tethered to the clinical outcomes
      medical education aims to achieve. They focus on a specific clinical outcome
      maternal complications of obstetrical delivery-and show how examining various
      observable elements of physicians' training and experience helps reveal which of
      those elements lead to better outcomes. Does it matter where obstetricians
      trained? Does it matter how much experience they have? Does it matter how good
      they were to start? Each of these questions reflects a component of the
      production of a good obstetrician and, most important, defines a good
      obstetrician as one whose patients in the end do well. 

PMID- 24280860
TI  - Demonopolizing medical knowledge.
AB  - In the past 100 years, there has been an explosion of medical knowledge-and in
      the next 50 years, more medical knowledge will be available than ever before.
      Regrettably, current medical practice has been unable to keep pace with this
      explosion of medical knowledge. Specialized medical knowledge has been confined
      largely to academic medical centers (i.e., teaching hospitals) and to specialists
      in major cities; it has been disconnected from primary care clinicians on the
      front lines of patient care. To bridge this disconnect, medical knowledge must be
      demonopolized, and a platform for collaborative practice amongst all clinicians
      needs to be created. A new model of health care and education delivery called
      Project ECHO (Extension for Community Healthcare Outcomes), developed by the
      first author, does just this. Using videoconferencing technology and case-based
      learning, ECHO's medical specialists provide training and mentoring to primary
      care clinicians working in rural and urban underserved areas so that the latter
      can deliver the best evidence-based care to patients with complex health
      conditions in their own communities. The ECHO model increases access to care in
      rural and underserved areas, and it demonopolizes specialized medical knowledge
      and expertise. 

PMID- 24280861
TI  - The accreditation system after the "next accreditation system".
AB  - The Accreditation Council for Graduate Medical Education (ACGME) and the American
      Board of Medical Specialties and its member boards introduced the six domains of
      physician competency in 1999. This initiated a national dialogue concerning the
      elements of competency of the physician, and incorporation of these elements into
      the framework of evaluation of residents and fellows, as well as the educational
      programs within which they are trained. The next step in this process will be the
      ACGME's Next Accreditation System, which the authors describe in this commentary.
      Recognizing that there are already developments in the assessment of medical
      education that will influence future models of accreditation, the authors
      consider some of these innovations and discuss how they may shape the next
      accreditation system after the Next Accreditation System. 

PMID- 24280862
TI  - Necessity is the mother of invention: video recording firsthand perspectives of
      critical medical procedures to make simulated training more effective.
AB  - The traditional apprenticeship model for training doctors requires ample
      opportunities in the clinic for trainees to learn core procedures under the
      supervision of skilled doctors. In this issue, Kyser and colleagues document that
      the learning opportunities for residents to master certain core procedures, such
      as forceps and vacuum deliveries, are insufficient in many teaching hospitals. To
      address this serious problem, this author argues that learning techniques (i.e.,
      deliberate practice and simulator use) from other domains of expertise, such as
      chess, music, and sports, must be adapted for use in medicine. For example,
      medical procedures should be videotaped and indexed for access over the Internet.
      Trainees then could view recordings of rare emergency procedures and
      complications and practice their decision-making skills. Evidence suggests that
      training outside the constraints of the clinic could be more effective in
      improving performance because trainees are able to engage in deliberate practice
      and focus on their individual weaknesses in executing procedures and making
      decisions. For example, with video and simulator training, trainees have the
      opportunity to repeatedly perform only the parts of a procedure that they find
      challenging until they have attained a level of acceptable speed and control.
      More generally, training could be structured around the particular needs of
      individual learners and scheduled when the learners are rested and able to
      concentrate fully on learning. Training also should include opportunities for
      learners to practice repeatedly with different patient descriptions requiring the
      same or different, yet related, procedures to teach trainees effective
      discrimination and execution. 

PMID- 24280863
TI  - MD-PhD training: looking back and looking forward.
AB  - MD-PhD programs provide rigorous, integrated training for physician-scientists,
      enabling them to frame scientific questions in unique ways and to apply clinical
      insight to fundamental science. Few would question the influential contributions
      of MD-PhD physician-scientists in advancing medical science. In this issue of
      Academic Medicine, Jeffe et al affirm high levels of excellence in educational
      outcomes from MD-PhD training programs at U.S. MD-granting medical schools,
      especially programs that receive funding from the NIH Medical Scientist Training
      Program (MSTP). The author of this commentary observes that, in the face of
      current economic pressures, comprehensive, longitudinal national outcomes data
      from MSTP- and non-MSTP-funded MD-PhD programs will help verify the value
      provided by MD-PhD physician-scientists. She proposes that MD-PhD programs should
      better prepare the next generation of physician-scientists for future research
      environments, which will provide new technologies, venues, and modalities. These
      research environments will be more closely integrated within health care delivery
      systems, extend into diverse communities and regions, and employ complex
      technologies. MD-PhD physician-scientists also will train and gain expertise in
      broadening areas of research, such as health policy, health economics, clinical
      epidemiology, and medical informatics. Program leaders are ideally situated to
      foster innovative learning environments and methodologies. By sharing their
      innovations, they can help ensure production of a diverse MD-PhD physician
      scientist workforce, prepared to engage in myriad research opportunities to meet
      patient and population needs in a new environment. 

PMID- 24280864
TI  - Thymic epithelial cell expansion through matricellular protein CYR61 boosts
      progenitor homing and T-cell output.
AB  - Thymic epithelial cells (TEC) are heterogeneous stromal cells that generate
      microenvironments required for the formation of T cells within the thymus.
      Defects in TEC lead to immunodeficiency or autoimmunity. Here we identify TEC as
      the major source of cysteine-rich protein 61 (CYR61), a matricellular protein
      implicated in cell proliferation and migration. Binding of CYR61 to LFA-1, ICAM-1
      and integrin alpha6 supports the adhesion of TEC and thymocytes as well as their
      interaction. Treatment of thymic lobes with recombinant CYR61 expands the stromal
      compartment by inducing the proliferation of TEC and activates Akt signalling.
      Engraftment of CYR61-overexpressing thymic lobes into athymic nude mice
      drastically boosts the yield of thymic output via expansion of TEC. This
      increases the space for the recruitment of circulating hematopoietic progenitors
      and the development of T cells. Our discovery paves the way for therapeutic
      interventions designed to restore thymus stroma and T-cell generation. 

PMID- 24280865
TI  - Tandem synthesis of 3-allyl-chromones from alkynones and allylic alcohols under
      metal-free conditions.
AB  - A novel and efficient approach to 3-allyl-chromones from alkynones and allylic
      alcohols via a tandem Michael addition-Claisen rearrangement-O-arylation reaction
      has been developed. Diversely structural 3-allyl-chromones were afforded in up to
      93% yield for 24 examples. This synthetic strategy is regiospecific, highly
      efficient, environment friendly and metal-free. 

PMID- 24280866
TI  - Differential expression of miR-17~92 identifies BCL2 as a therapeutic target in
      BCR-ABL-positive B-lineage acute lymphoblastic leukemia.
AB  - Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute
      lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the
      development of novel treatment strategies. As the known oncomir, miR-17~92, is
      regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its
      role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly
      less abundant in BCR-ABL-positive as compared to -negative ALL-cells and
      overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner.
      Stable isotope labelling of amino acids in culture (SILAC) followed by liquid
      chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related
      proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as
      a direct target of this miRNA cluster in mice and humans, and, similar to miR
      17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL
      positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more
      sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a
      xenograft model using patient-derived leukaemic blasts, real-time, in vivo
      imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic
      strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in
      regulation of apoptosis, and identify BCL2 as a therapeutic target of particular
      relevance in BCR-ABL-positive ALL.

PMID- 24280867
TI  - Cyclophosphamide as a first-line therapy in LGL leukemia.

PMID- 24280868
TI  - Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia
      cells by targeting the cytoskeleton.
AB  - Chronic lymphocytic leukemia (CLL) is an incurable malignancy of mature B cells.
      One of the major challenges in treatment of CLL is the achievement of a complete
      remission to prevent relapse of disease originating from cells within lymphoid
      tissues and subsequent chemoresistance. In search for novel drugs that target CLL
      cells in protective microenvironments, we performed a fungal extract screen using
      cocultures of primary CLL cells with bone marrow-derived stromal cells. A
      secondary metabolite produced by Penicillium aquamarinium was identified as
      Chaetoglobosin A (ChA), a member of the cytochalasan family that showed
      preferential induction of apoptosis in CLL cells, even under culture conditions
      that mimic lymphoid tissues. In vitro testing of 89 CLL cases revealed effective
      targeting of CLL cells by ChA, independent of bad prognosis characteristics, like
      17p deletion or TP53 mutation. To provide insight into its mechanism of action,
      we showed that ChA targets filamentous actin in CLL cells and thereby induces
      cell-cycle arrest and inhibits membrane ruffling and cell migration. Our data
      further revealed that ChA prevents CLL cell activation and sensitizes them for
      treatment with PI3K and BTK inhibitors, suggesting this compound as a novel
      potential drug for CLL. 

PMID- 24280870
TI  - Polymeric nanotherapeutics: clinical development and advances in stealth
      functionalization strategies.
AB  - Long-circulating polymeric nanotherapeutics have garnered increasing interest in
      research and in the clinic owing to their ability to improve the solubility and
      pharmacokinetics of therapeutic cargoes. Modulation of carrier properties
      promises more effective drug localization at the disease sites and can lead to
      enhanced drug safety and efficacy. In the present review, we highlight the
      current development of polymeric nanotherapeutics in the clinic. In light of the
      importance of stealth properties in therapeutic nanoparticles, we also review the
      advances in stealth functionalization strategies and examine the performance of
      different stealth polymers in the literature. In addition, we discuss the recent
      development of biologically inspired "self" nanoparticles, which present a
      differing stealth concept from conventional approaches. 

PMID- 24280869
TI  - Epimutations mimic genomic mutations of DNMT3A in acute myeloid leukemia.
AB  - Mutations in the genetic sequence of the DNA de novo methyltransferase DNMT3A
      (DNA methyltransferase 3A) are found in many patients with acute myeloid leukemia
      (AML). They lead to dysfunction of DNMT3A protein and represent a marker for poor
      prognosis. Effects of genetic mutations can be mimicked by epigenetic
      modifications in the DNA methylation (DNAm) pattern. Using DNAm profiles of the
      Cancer Genome Atlas Research Network (TCGA), we identified aberrant
      hypermethylation at an internal promoter region of DNMT3A, which occurred in
      about 40% of AML patients. Bisulfite pyrosequencing assays designed for this
      genomic region validated hypermethylation specifically in a subset of our AML
      samples. High DNAm levels at this site are particularly observed in samples
      without genetic mutations in DNMT3A. Epimutations and mutations of DNMT3A were
      associated with related gene expression changes such as upregulation of the
      homeobox genes in HOXA and HOXB clusters. Furthermore, epimutations in DNMT3A
      were enriched in patients with poor or intermediate cytogenetic risk, and in
      patients with shorter event-free survival and overall survival (OS). Taken
      together, aberrant DNA hypermethylation within the DNMT3A gene, in analogy to
      DNMT3A mutations, is frequently observed in AML and both modifications seem to be
      useful for risk stratification or choice of therapeutic regimen. 

PMID- 24280872
TI  - Association between higher BMI and depressive symptoms in Icelandic adolescents:
      the mediational function of body image.
AB  - BACKGROUND: Weight status and depressive affect in adolescents are positively
      related constructs, but the nature of this relationship is not well understood,
      especially in European populations. The objective of this study was to examine
      the interplay between body mass index (BMI) and depressive symptoms, while
      accounting for the possible mediational role of body image, in a sample of older
      adolescents in Iceland. METHOD: We utilized data from a population-based cross
      sectional sample of 11 388 junior college students (16-20-year-olds) to conduct
      structural equation modelling to test the relationship between BMI, body image
      and depressive symptoms while controlling for socioeconomic status and other
      background variables. RESULTS: Higher levels of BMI are associated with higher
      depressive symptoms. However, this association was mediated entirely through
      perceptions of body image. The association is gender dependent, with the
      relationship between BMI levels and depressive symptoms being significantly
      stronger among junior college girls than boys. CONCLUSION: Body image is a key
      contributor in the relationship between weight status and depressive symptoms
      among adolescents. Future interventions with adolescents should take this
      association into account and focus on such factors as physical confidence and
      self-esteem.

PMID- 24280871
TI  - Sleep duration does not mediate or modify association of common genetic variants
      with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Short and long sleep duration are associated with increased risk
      of type 2 diabetes. We aimed to investigate whether genetic variants for fasting
      glucose or type 2 diabetes associate with short or long sleep duration and
      whether sleep duration modifies the association of genetic variants with these
      traits. METHODS: We examined the cross-sectional relationship between self
      reported habitual sleep duration and prevalence of type 2 diabetes in individuals
      of European descent participating in five studies included in the Candidate Gene
      Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested
      for association of 16 fasting glucose-associated variants, 27 type 2 diabetes
      associated variants and aggregate genetic risk scores with continuous and
      dichotomised (<=5 h or >=9 h) sleep duration using regression models adjusted for
      age, sex and BMI. Finally, we tested whether a gene * behaviour interaction of
      variants with sleep duration had an impact on fasting glucose or type 2 diabetes
      risk. RESULTS: Short sleep duration was significantly associated with type 2
      diabetes in CARe (OR 1.32; 95% CI 1.08, 1.61; p = 0.008). Variants previously
      associated with fasting glucose or type 2 diabetes and genetic risk scores were
      not associated with sleep duration. Furthermore, no study-wide significant
      interaction was observed between sleep duration and these variants on glycaemic
      traits. Nominal interactions were observed for sleep duration and PPARG
      rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2
      diabetes (p < 0.05). CONCLUSIONS/INTERPRETATION: Our findings suggest that
      differences in habitual sleep duration do not mediate or modify the relationship
      between common variants underlying glycaemic traits (including in circadian
      rhythm genes) and diabetes.

PMID- 24280873
TI  - Association between socioeconomic factors and sleep quality in an urban
      population-based sample in Germany.
AB  - BACKGROUND: Good sleep quality is essential for recovery. The risk factors of
      sleep disorders have been extensively investigated, but there is sparse
      information on the association of socioeconomic factors with a person's sleep
      quality. The aim of the present analysis is to investigate this association,
      taking particularly the effect of health confounders into consideration. METHODS:
      The data were extracted from the cross-sectional QUEBEB Study. In total, the
      study sample consisted of 3281 participants (1817 women and 1464 men, aged 16-72
      years). Here socioeconomic status (SES) was collected from the baseline survey
      taken in 2004. Sleep quality for the same participants was measured with in-depth
      personal interviews in 2006 using the Pittsburgh Sleep Quality Index, together
      with other relevant characteristics (e.g. anxiety, depression and health status).
      Multiple logistic regression analyses were performed. RESULTS: People living in
      an urban environment with a high or medium SES have a greater probability of good
      sleep quality (odds ratio 1.65, 95% confidence interval 1.27-2.14; odds ratio
      1.40, 95% confidence interval 1.16-1.69) than persons with a low SES. Anxiety and
      depression, but also health status, are also associated with sleep quality and
      can influence in part the socioeconomic levels seen in sleep quality. CONCLUSION:
      SES and sleep quality are associated. However, there are important additional
      determinants that influence the level of association between SES and sleep
      quality. Several factors, such as anxiety, depression and health status, are
      associated with poorer sleep quality, but at the same time, these factors occur
      more often within lower social classes.

PMID- 24280874
TI  - FOXE1 and SYNE1 genes hypermethylation panel as promising biomarker in colitis
      associated colorectal neoplasia.
AB  - BACKGROUND: Colitis-associated colorectal cancer affects individuals with
      inflammatory bowel disease (IBD) more often and earlier than cancer in the
      general population. Colonoscopy provides the surveillance gold standard. Changes
      to the surveillance intervals depending on endoscopic activity have been made,
      given data demonstrating that this is an important predictor of future dysplasia
      or cancer, but adjuvant, noninvasive clinical tools are still warranted to
      improve surveillance outcomes and to assist in management and interpretation of
      dysplasia. Methylation markers may be able to do this. METHODS: SYNE1, FOXE1,
      NDRG4, and PHACTR3 genes were screened using methylation-specific PCR that permit
      the methylation status of the genes to be determined directly on biopsies. Ninety
      three patients with long-standing IBD undergoing a cancer surveillance program,
      and 30 healthy controls were studied. These included colorectal adenocarcinomas
      on a background of IBD of various stages (n = 25), IBD-associated dysplastic
      lesions (n = 29), adenomas arising on a background of ulcerative colitis (n = 8),
      samples from patients with no evidence of dysplasia or cancer but long-standing
      IBD (n = 31), and symptomatic patients found to have normal colonoscopy
      (controls) (n = 30). RESULTS: Gene promotor hypermethylation of SYNE1 and FOXE1
      genes varied significantly between the groups and was increasingly likely with
      increased disease severity. Neither occurred in controls, whereas promotor
      hypermethylation was detected in biopsies of 60% of patients with colitis
      associated colorectal cancer for FOXE1 and 80% for SYNE1. Promotor
      hypermethylation of either gene was highly significantly different between the
      groups overall. CONCLUSIONS: FOXE1 and SYNE1 hypermethylation markers
      demonstrated significantly increased expression in neoplastic tissue. Promoter
      methylation analysis of these genes might be a useful marker of neoplasia in long
      standing IBD.

PMID- 24280875
TI  - Risk matrix for prediction of advanced disease in a population-based study of
      patients with Crohn's Disease (the IBSEN Study).
AB  - BACKGROUND: Identifying patients with Crohn's disease with increased risk of
      subsequent complications is essential for appropriate treatment. Based on
      exploratory analysis, we developed a prediction model for assessing the
      probability of developing advanced disease 5 and 10 years after diagnosis.
      METHODS: A population-based cohort of 237 patients with Crohn's disease diagnosed
      from 1990-1994 was followed for 10 years. In the 5-year analysis, advanced
      disease was defined as having intestinal resection, progression in disease
      behavior, or need for thiopurines. The analysis was limited to patients with
      uncomplicated disease at diagnosis who were alive (n = 140), excluding those who
      were lost during follow-up (n = 8). For the 10-year analysis, advanced disease
      was defined as having surgery, excluding those who had surgery within the first
      30 days (n = 7), those who died (n = 18), or were lost during follow-up (n = 22).
      Based on the best fitted multiple model, the probabilities of advanced disease
      were computed for selected baseline levels of the covariates and the results were
      arranged in a prediction matrix. Except for ASCA, all predictors were measured at
      diagnosis. RESULTS: ASCA status, disease location, age, and need for systemic
      steroids were included in the 5-year prediction matrix. The probabilities of
      advanced disease during this period varied from 8.6% to 92.0% depending on the
      combination of predictors. The 10-year matrix combined ASCA status, disease
      behavior, age, and need for systemic steroids; the probabilities of advanced
      disease ranged from 12.4% to 96.7%. CONCLUSIONS: Our prediction models revealed
      substantial differences in the probability of developing advanced disease in the
      short and intermediate course of Crohn's disease, suggesting that a model-based
      prediction matrix is useful in early disease management.

PMID- 24280876
TI  - Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel
      disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Methotrexate (MTX) is an immunomodulator used in pediatric
      inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is
      associated with liver toxicity. We aimed to systematically review and meta
      analyze the incidence of hepatotoxicity with MTX use among children with IBD.
      METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central
      Register of Controlled Trials databases from 1946 to April 2013 for cohort
      studies and collected information about the study design, IBD treatment results,
      and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval
      (CI) were estimated using a random-effects model. RESULTS: Twelve high-quality
      studies were included in this review. Fifty-seven of 457 patients treated with
      MTX developed varied degrees of abnormal liver biochemistry. The pooled
      proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%
      18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity,
      dose reductions were required in 6.4% (95% CI 4.3%-9.5%), whereas 4.5% (95% CI
      2.8%-7.2%) of patients required discontinuation. CONCLUSIONS: Hepatotoxicity
      after the use of MTX among IBD patients was a relatively common event. Monitoring
      for hepatotoxicity is strongly recommended, as discontinuation of MTX may be
      necessary in a significant proportion of children.

PMID- 24280877
TI  - Effect of probiotics on inducing remission and maintaining therapy in ulcerative
      colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Whether probiotics are beneficial at all stages of treatment in
      inflammatory bowel disease or superior to placebo remains controversial. METHODS:
      Two reviewers independently selected randomized controlled trials comparing
      probiotics with controls in inflammatory bowel disease and extracted data related
      to remission/response rates, relapse rates, and adverse events. Subanalyses were
      also performed. RESULTS: Twenty-three randomized controlled trials with a total
      of 1763 participants met the inclusion criteria. From the meta-analysis,
      probiotics significantly increase the remission rates in patients with active
      ulcerative colitis (UC) (P = 0.01, risk ratio [RR] = 1.51). The remission rates
      were significantly higher in patients with active UC treated with probiotics than
      placebo (P < 0.0001, RR = 1.80). Unfortunately, subgroup analysis found that only
      VSL#3 significantly increased the remission rates compared with controls in
      patients with active UC (P = 0.004, RR = 1.74). Interestingly, VSL#3 (P <
      0.00001, RR = 0.18) also significantly reduced the clinical relapse rates for
      maintaining remission in patients with pouchitis. No significantly different
      adverse events were detected between probiotics and controls in the treatment of
      UC (P = 0.94, RR = 0.99) or CD (P = 0.33, RR = 0.87). CONCLUSIONS: Administration
      of probiotics results in additional benefit in inducing remission of patients
      with UC. VSL#3 are beneficial for maintaining remission in patients with
      pouchitis. And, probiotics can provide the similar effect as 5-aminosalicylic
      acid on maintaining remission of UC, although no additional adverse events
      presented.

PMID- 24280878
TI  - Prednisolone but not infliximab aggravates the upregulated hepatic nitrogen
      elimination in patients with active inflammatory bowel disease.
AB  - BACKGROUND: Catabolism and weight loss are serious problems in patients with
      active inflammatory bowel disease (IBD). The body nitrogen (N) depletion is
      partly related to increased hepatic capacity for the elimination of N through
      urea synthesis. This is probably caused by the inflammation per se, and the
      treatment with prednisolone may aggravate the problem, whereas the effect of
      biological therapy is unknown. Therefore, we examined the effects of prednisolone
      or infliximab on the regulation of urea synthesis in patients with active IBD.
      METHODS: Urea synthesis was quantified by the functional hepatic nitrogen
      clearance (FHNC), i.e., the slope of the linear relationship between the urea
      nitrogen synthesis rate and the blood alpha-amino nitrogen concentration during
      alanine infusion. Thirty-seven patients with active IBD treated with either
      prednisolone or infliximab were examined before and after 7 days of treatment.
      RESULTS: At baseline, the FHNC was similar in the 2 treatment groups (36 L/h).
      After 7 days, prednisolone increased the FHNC by 40% (55 L/h) (P = 0.03), whereas
      infliximab tended to reduce the FHNC by 15% (30 L/h) (P = 0.09). The changes in
      the FHNC differed significantly between the 2 treatment groups (P < 0.01).
      CONCLUSIONS: Prednisolone treatment further upregulated urea synthesis, which
      increases the hepatic loss of nitrogen and promotes body catabolism. In contrast,
      infliximab treatment caused no such aggravation and likely reduced the N loss.
      These results may argue in favor of infliximab therapy for IBD and add to the
      pathophysiological understanding of the interplay between inflammation,
      catabolism, and anti-inflammatory treatment.

PMID- 24280879
TI  - Antibodies to infliximab and risk of infusion reactions in patients with
      inflammatory bowel disease: a systematic review and meta-analysis.
AB  - OBJECTIVES: Antibodies to infliximab (ATIs) have been associated with a risk of
      infusion reactions in some studies of patients with inflammatory bowel disease.
      However, many factors, such as immunomodulators and dosing schedule, may
      influence this association. The aim of this article was to provide a pooled
      estimate of the risk of infusion reactions according to patients' ATI status and
      analyze the relationship of immunomodulators to this risk. DESIGN: Public
      databases were searched for eligible studies. Quality assessment was undertaken
      for all studies using Grading of Recommendations Assessment, Development and
      Evaluation criteria. Raw data from studies meeting inclusion criteria were pooled
      for meta-analysis of effect estimates. Sensitivity analysis was performed for all
      outcomes. Funnel plot was performed to assess for publication bias. RESULTS:
      Eight studies met the inclusion criteria, with a pooled total of 1351 subjects.
      Seven of the 8 studies had a high risk of bias in at least 1 quality domain. The
      cumulative data indicated that there was a higher risk ratio (RR) of any acute
      infusion reaction (RR 2.4; 95% confidence interval [CI] 1.5-3.8, P < 0.001) and
      severe infusion reactions (RR 5.8, 95% CI 1.7-19, P = 0.004) in patients with
      ATIs when compared with patients without ATIs. The RR of delayed hypersensitivity
      reactions was not significantly different between ATI+ and ATI- patients (RR 2.8,
      95% CI 0.2-33, P = 0.4). Patients prescribed immunomodulators during maintenance
      infliximab therapy had a reduction in their risk for ATI development (RR 0.6, 95%
      CI 0.4-0.9, P = 0.02) and infusion reactions (RR 0.6, 95% CI 0.4-0.8, P < 0.001).
      CONCLUSIONS: The presence of ATIs is associated with a significantly higher risk
      of acute infusion reactions, but not delayed hypersensitivity reactions, in
      patients with inflammatory bowel disease. Concomitant immunomodulators reduce
      this risk.

PMID- 24280880
TI  - Sight-threatening keratopathy complicating anti-TNF therapy in Crohn's disease: a
      case report.

PMID- 24280881
TI  - Patient preferences for surgical versus medical therapy for ulcerative colitis.
AB  - BACKGROUND: Therapy options for mesalamine-refractory ulcerative colitis (UC)
      include immunosuppressive medications or surgery. Chronic immunosuppressive
      therapy increases risks of infection and cancer, whereas surgery produces a
      permanent change in bowel function. We sought to quantify the willingness of
      patients with UC to accept the risks of chronic immunosuppression to avoid
      colectomy. METHODS: We conducted a state-of-the-art discrete-choice experiment
      among 293 patients with UC who were offered a choice of medication or surgical
      treatments with different features. Random parameters logit was used to estimate
      patients' willingness to accept trade-offs among treatment features in selecting
      surgery versus medical treatment. RESULTS: A desire to avoid surgery and the
      surgery type (ostomy versus J-pouch) influenced patients' choices more than a
      specified range of 10-year mortality risks from lymphoma or infection, or disease
      activity (mild versus remission). To avoid an ostomy, patients were willing to
      accept a >5% 10-year risk of dying from lymphoma or infection from medical
      therapy, regardless of medication efficacy. However, data on patients' stated
      choice indicated perceived equivalence between J-pouch surgery and incompletely
      effective medical therapy. Patient characteristics and disease history influenced
      patients' preferences regarding surgery versus medical therapy. CONCLUSIONS:
      Patients with UC are willing to accept relatively high risks of fatal
      complications from medical therapy to avoid a permanent ostomy and to achieve
      durable clinical remission. However, patients view J-pouch surgery, but not
      permanent ileostomy, as an acceptable therapy for refractory UC in which medical
      therapy is unable to induce a durable remission.

PMID- 24280884
TI  - Is impact factor necessary for "Prilozi (Contributions)" and Macedonia?
AB  - 58 years after the creation of impact factor (IF) the professional public shows
      interest in IFs and their significance for academia and individuals. Really, is a
      medical journal with IF needed for Macedonia? Some other small and developing
      countries have pursued and accomplished this goal: Serbia, Slovenia, and Croatia.
      On the other hand the survey of publications in Macedonian medical journals has
      been found to lack quality. We believe that to strive to obtain an IF would be
      beneficial for all Macedonian interest groups involved. This would introduce an
      ambition among the members of Macedonian academia to publish (so far rare), than
      to publish in Pubmed listed journals (ambition present in very few Macedonian
      academics) and then to publish in journals with the highest IF possible (so far a
      very exclusive group of Macedonian medical professionals). In time this will help
      in creating and enforcing legal obligation for the academia for a promotion based
      on merit of IF scientific publications. We believe that this is possible only by
      Parliament legislation. This will be of benefit for Macedonian patients, the
      medical community and will unable this country to contribute to the universe of
      science. Lastly it would certainly be helpful in getting a Macedonian university
      in the prestigious first 500 Shangai list. Key words: impact factor, Macedonia,
      medical journals.

PMID- 24280883
TI  - Novel Rho/MRTF/SRF inhibitors block matrix-stiffness and TGF-beta-induced
      fibrogenesis in human colonic myofibroblasts.
AB  - BACKGROUND: Ras homolog gene family, member A (RhoA)/Rho-associated coiled-coil
      forming protein kinase signaling is a key pathway in multiple types of solid
      organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects
      of RhoA/Rho-associated coiled-coil forming protein kinase signaling have
      frustrated targeted drug discovery efforts. Recent recognition of the role of Rho
      regulated gene transcription by serum response factor (SRF) and its
      transcriptional cofactor myocardin-related transcription factor A (MRTF-A)
      suggest a novel locus for pharmacological intervention. METHODS: Because RhoA
      signaling is mediated by both physical and biochemical stimuli, we examined
      whether pharmacological inhibition of RhoA or the downstream transcription
      pathway of MRTF-A/SRF could block intestinal fibrogenesis in 2 in vitro models.
      RESULTS: In this study, we demonstrate that inhibition of RhoA signaling blocks
      both matrix-stiffness and transforming growth factor beta-induced fibrogenesis in
      human colonic myofibroblasts. Repression of alpha-smooth muscle actin and
      collagen expression was associated with the inhibition of MRTF-A nuclear
      localization. CCG-1423, a first-generation Rho/MRTF/SRF pathway inhibitor,
      repressed fibrogenesis in both models, yet has unacceptable cytotoxicity. Novel
      second-generation inhibitors (CCG-100602 and CCG-203971) repressed both matrix
      stiffness and transforming growth factor beta-mediated fibrogenesis as determined
      by protein and gene expression in a dose-dependent manner. CONCLUSIONS: Targeting
      the Rho/MRTF/SRF mechanism with second-generation Rho/MRTF/SRF inhibitors may
      represent a novel approach to antifibrotic therapeutics.

PMID- 24280885
TI  - The improvement in kidney transplant program in R. Macedonia--what are the clues?
AB  - Kidney transplantation (KTx) is the best treatment option in patients with
      chronic kidney disease (CKD). Health-economics data favour the KTx in comparison
      with any type of dialysis procedure, but the multidisciplinary approach and
      required high level of organisational infrastructure are frequent impediments for
      its availability in the majority of developing countries. A living donor kidney
      transplant (LDKTx) programme has been developed in the Republic of Macedonia
      since 1977 but without a real continuum in the following years. There was a great
      success with 15 cadaveric kidneys transplanted (1987-1989) followed by an average
      of 13.5 KTx per year in the period 1996-2011. Because of the scarce organ
      donation and transplant activities in the majority of Balkan countries the
      question remains what could be done in order to enable organ transplantation as
      the basic human right for the best treatment option in patients with CKD. In
      addition to the possible increase in the number of LDKTx, prerequisites for a
      deceased donor (DD) programme would be the creation of an official waiting list
      of candidates for DD transplantation, organizational and infrastructural
      networking and raising public awareness on the number of potential deceased
      donors through permanent media presentation. Our involvement in the South-eastern
      Europe Health Network (SEEHN) initiative and the support from the newly created
      Regional Health Development Centre (RHDC) on Organ Donation and Transplant
      Medicine established in Croatia (Zagreb) was shown as successful for improvement
      of the KTx programme. At the very first professional meeting (27-28 May, 2011 in
      Skopje, Macedonia), the organ donation and transplantation needs of each country
      within the SEE geographical region were addressed and action plans for further
      steps on how to proceed were established. Hence, the number of professionals
      (including vascular surgeons) involved in KTx was increased along with the
      substantial increase in the reimbursement per transplant procedure at the Urology
      Department. Nowadays, we are pleased to report 24 successfully performed LDKTx in
      2012, and in 2013 for 7 months 28 transplantations, awaiting 40 KTx at the end of
      the year. Prospectively, we should initiate the deceased donor programme, even in
      order to sustain the already established high number of transplantation per
      month/year, since the potential for LDKTx may be exhausted. We also hope to be
      supportive for regional collaboration and transplantation of CKD patients from
      the neighbouring countries (Albania and Kosovo), and eventually to establish
      regional networking in deceased donor procurement, exchange and allocation
      practice.

PMID- 24280882
TI  - Challenges in designing a national surveillance program for inflammatory bowel
      disease in the United States.
AB  - This review describes the history of U.S. government funding for surveillance
      programs in inflammatory bowel diseases (IBD), provides current estimates of the
      incidence and prevalence of IBD in the United States, and enumerates a number of
      challenges faced by current and future IBD surveillance programs. A rationale for
      expanding the focus of IBD surveillance beyond counts of incidence and
      prevalence, to provide a greater understanding of the burden of IBD, disease
      etiology, and pathogenesis, is provided. Lessons learned from other countries are
      summarized, in addition to potential resources that may be used to optimize a new
      form of IBD surveillance in the United States. A consensus recommendation on the
      goals and available resources for a new model for disease surveillance are
      provided. This new model should focus on "surveillance of the burden of disease,"
      including (1) natural history of disease and (2) outcomes and complications of
      the disease and/or treatments.

PMID- 24280886
TI  - Antibiotics for upper respiratory infections: public knowledge, beliefs and self
      medication in the Republic of Macedonia.
AB  - Self-medication as part of the irrational use of antibiotics contributes to the
      spread of antimicrobial resistance. The aim of this community-based survey in
      Macedonia was to determine public knowledge, beliefs and self-medication with
      antibiotics for upper respiratory infections. A cross-sectional study was
      conducted in three administrative regions in Macedonia in April 2012. 402
      eligible participants answered an anonymous questionnaire. The analysis of
      answers involved descriptive quantitative statistics (frequencies and
      percentages). We also tested for significant associations between demographic
      characteristics and non-prescription use of antibiotics. Our respondents
      demonstrated a relatively low level of public knowledge about antibiotics and
      upper respiratory infection treatments in comparison to the EU countries. The
      study found that 71.4% of participants stored antibiotics at home, and 43.3%
      purchased antibiotics over-the-counter in the last year, despite national
      regulation that restricts antibiotics as prescription-only medicines. Actual self
      medication with antibiotics for a recent upper respiratory infection episode was
      reported in 17.8% of adults and 1.8% of children aged 0-4 years. We did not find
      any significant association between participants demography and non-prescription
      use of antibiotics. Our results put in the group of eastern and southern EU
      countries with the highest rates for non-prescription use of antibiotics in
      Europe. Multifaceted interventions are needed to prevent self-medication with
      antibiotics, including: enforcement of regulations that restrict over-the-counter
      sales of antibiotics, monitoring of antibiotic use and antimicrobial resistance
      rates and combined public education strategies.

PMID- 24280887
TI  - Perceived stress in dental practice.
AB  - Stress is a normal physiological response to events that make us feel threatened,
      or upset our balance in some way. In medicine, it is known that stress, as an
      emotional state, can be a trigger for many psychosomatic disorders. Work stress
      and burnout are considered to be serious professional risks in dentistry. The
      dentist should be aware of these stressors and attempt to manage them in order to
      avoid becoming occupationally dissatisfied. On the other hand, the other common
      characteristic of modern life is a growing burden of different chronic diseases.
      Periodontal disease is one of the two most important oral diseases contributing
      to the global burden of chronic disease. The aim of this study was to assess the
      perceived stress in patients with periodontal pathologies, and to compare it with
      the stress in doctors-dentists and students of dentistry as future professionals.
      Our study confirmed the presence of significant stress in all three groups of
      examinees (patients, doctors, and students). Surprisingly, the obtained PSQ
      scores are similar in the examined groups. In addition, no differences between
      perceived stress in males and females have been found. There is a minimal
      positive correlation between age and obtained scores. However, stress must be
      evaluated as a risk factor both for professionals or for chronic dental patients
      and some response measures must be undertaken.

PMID- 24280888
TI  - T-cell subpopulations in lesions of oral lichen planus.
AB  - AIM OF THE STUDY: To determine the distribution and frequency of T(CD3) cells and
      cell sub-populations in tissue specimens of erosive lichen planus (EOLP).
      MATERIAL AND METHOD: Tissue specimens from buccal mucosa were taken from 14
      healthy individuals--control group (CG)--and 17 subjects with EF-OLP. Applying
      monoclonal antibodies, T(CD3) cells, T cell subpopulations, The CD4, CD8 and
      CD4/CD8 ratios in both groups were determined. Cells in the epithelium and lamina
      propria were quantitatively and qualitatively determined in both groups. Data
      were analysed using the Student's t-test. RESULTS: There were 5.95 2.12% T(CD3)
      cells in the control group as against 9.80 4.04% in the examined group (p<0.001).
      The distribution of T(CD3) cells in the lamina propria was 25.35 12.04% in the
      examined group compared to the control group (p<0.001). There were 3.45 2.05% CD4
      epithelial cells in the control group and 4.00 1.95% in the examined group
      (p<0.4). There were 2.50 1.8% CD8 cells in the control group and 5.80 3.72% in
      the examined group (p<0.001). The CD4/CD8 ratio was 0.51 0.12% in the examined
      group and it was evidently reduced in comparison with the control group. An
      increased distribution of CD4 cells (10.30 7.60%) and CD8 cells (15.05 5.20%) in
      the lamina propria compared with the epithelium was observed in the examined
      group (p<0.001). The CD4/CD8 ratio in the epithelium was 0.51 0.12% as against
      the ratio of the lamina propria, which was slightly increased (0.68 0.48%) with a
      low statistically significant difference (p<0.05). CONCLUSION: Differences in the
      distribution of T-lymphocyte subsets between the control and examined groups were
      found (p<0.001). An increased distribution and frequency of CD4 and CD8 cells in
      the lamina propria was observed. These were predominantly located in the sub
      basal region of the stratum papillare and rarely seen in the intra-epithelial
      region.

PMID- 24280889
TI  - Evaluation of buffer capacity of saliva in caries-free and caries-active
      children.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between the
      physicochemical properties of saliva, such as buffering capacity, in caries-free
      and caries-active children. MATERIAL AND METHOD: Eighty children aged 12-14 years
      were included in this study. They were divided into two groups: a caries-free and
      a caries-active group, with 40 children in each group. Material for biochemical
      testing of saliva--a sample was taken from all subjects at different time
      intervals: 5, 30 and 60 minutes after the daily meal. The examined parameters
      were followed in the same examinees in a sample of saliva taken in the morning
      before consuming any food or implementation of oral hygiene: they represent basic
      information compared with the results of the examination. The concentration of
      salivary bicarbonates was determined by the enzyme method of continuous
      measurement. RESULTS: Salivary concentration of bicarbonates, measured fasting in
      the morning (basic values) in the caries-free group, ranging in limits from 6.60
      to 9.70 mmol/l, and significantly lower values in the caries-active group (from
      1.00 to 3.80 mmol/l). The same was the case with the concentration of salivary
      bicarbonates in different time intervals after taking the meal--5, 30 and 60
      minutes in the examined groups. By increasing the time interval after taking a
      meal, the concentration of salivary bicarbonates continuously and significantly
      declined compared to its baseline concentration. The largest decrease of
      concentration of bicarbonate in terms of its basic value in both examined groups
      (caries-free and caries-active) took place during the 60 minutes after having the
      meal. CONCLUSION: Salivary bicarbonates to maintaining the acidobasic balance of
      saliva, and thus affects the incidence of caries. The positive effect of salivary
      bicarbonates was confirmed by the values found in this study: the caries-free
      group presented a higher concentration of bicarbonate than the basic values. The
      value of bicarbonate in saliva in adolescents can serve as a parameter for
      determining the risk of caries, and this, in turn, can be used in the planning
      and implementation of appropriate caries-preventive measures.

PMID- 24280890
TI  - Pulp stones can help in detection of calculus in the kidneys and/or in the bile-
      fact or fiction?
AB  - BACKGROUND: Pulp stones or denticles are frequently found in the dental pulp;
      there is, however, scarce evidence about this phenomenon. Regardless of the
      obvious endodontic problem of inhibiting access to the canals and their further
      treatment, they have not been given great importance. The latest experiences of
      scientific and practical research, including examinations of dental
      calcifications and their association with calcifications/calculi in the organism,
      have not been included in the literature. AIM: To investigate the possible
      association between dental calcifications and calculi in the kidney and/or bile.
      METHODS: The study group included 200 patients diagnosed with pulptits chronica.
      All patients underwent dental and systematic examinations. Dental examination
      included x-rays, which detected the presence of calcifications in the dental
      pulps. Histopathological analysis of extirpated pulps was also made. Clinical
      examination comprised ultrasound that detected calculi. RESULTS: The results of
      the histopathological analysis of the extirpated pulps from the group of patients
      without denticles, but with calculi in their kidneys, bile and/or other organs,
      showed a regular presence of "sand" in large quantities in dental pulps. The
      presence of "sand" was depicted as presence of dystrophic calcifications. There
      was a percentage difference between the two groups: calculi in the organism
      (kidney and bile) and denticles--70% and calculi in the organism without
      denticles--30%. The Student's t-test showed a statistically significant
      difference for P=0.0000. This study defines the association between the calculi
      in the organism and the presence of dental calcifications, as well as their
      possible bacterial association.

PMID- 24280891
TI  - Multiple pathohisthological parameters influencing prognosis and survival of oral
      cancer patients.
AB  - The aim of this study is to determine the prognostic value of available clinical
      and histological parameters to predict subclinical nodal metastases and survival.
      For that purpose we used a modification of the Jakobsson [9] grading system
      proposed by Richard W. Nason [12] and applied it to a series of patients with
      oral carcinoma. Correlation between histological parameters and cervical lymph
      node metastasis were made and the chi-square test showed a strong significant
      association between mode of invasion, depth of tumor invasion, vascular invasion
      and cervical metastases. Analysis of overall survival showed that overall
      survival strongly correlates with cervical node metastases (p=0.0004). We found
      that overall survival correlates with vascular invasion (p=0.005) and also
      overall survival correlates with tumour depth (p=0.001). There is a strong
      relationship between malignancy score and survival (p=0.00001) and a high
      malignancy score is associated with poor prognoses. PATIENTS: a total 32 with
      over 14 points of malignancy score, 25 (78.1%) died and 7 (21.9%) are alive.
      Analysis of the risk factors for subclinical cervical metastases in patients with
      oral cancer is important for predicting prognosis and achieving a high survival
      rate.

PMID- 24280892
TI  - Multivisceral resection for advanced duodenal adenocarcinoma: a case report and
      review of literature.
AB  - The aim of this paper is to address adenocarcinoma of the duodenum by reporting a
      case, reviewing the literature and discussing current knowledge, diagnostic
      modalities and treatment options. We present a case of a 42-year-old patient with
      duodenal adenocarcinoma at the second portion invading surrounding organs. The
      patient had a previous history of colon malignancy and was diagnosed with a new
      tumour formation on regular CT (computed tomography) follow-up. Pylorus
      preserving pancreaticoduodenectomy (PPPD) was preformed for this T4 N2 M1 tumor.
      Duodenal adenocarcinoma is a rare tumor, most frequently involving the second
      duodenal portion. It has no specific symptoms and it is difficult to diagnose it
      due to its rarity and clinical presentation. Diagnosis, exact localization, and
      involvement of lymph nodes and surrounding organs have an impact on surgical
      strategy and prognosis.

PMID- 24280893
TI  - 20 years since the establishment of the BANTAO association (Balkan Cities
      Association of Nephrology, Dialysis, Transplantation and Artificial Organs).
AB  - The Balkan Cities Association of Nephrology, Dialysis, Transplantation and
      Artificial Organs (BANTAO) was born in Ohrid on October 9, 1993. The war in
      former Yugoslavia negatively affected the development of nephrology and also the
      connections among the nephrologists from the Balkans. However, there was
      willingness for further mutual collaboration between the nephrologists from the
      Balkans. The war in Yugoslavia created hate among people, between the newly
      established countries, and there were problems with the recognition of the names
      of the new countries, and so, the nephrologists decided to apply the ancient
      principle of using the names of the cities, instead of the countries, as the
      founders of the Association. The main goal of BANTAO is to promote scientific and
      technical cooperation in the fields of renal disease and artificial organs
      between the regions on the Balkan Peninsula and the world, to give an opportunity
      for exchange of experience and knowledge among the experts in the area and to
      engage in collaborative projects in order to demonstrate that cooperation is
      possible even on the turbulent Balkan Peninsula. The I BANTAO congress was held
      in Varna from September 22 to 24th, 1995 (President--D. Nenov, Varna). The II
      congress of BANTAO was held from September 6th to 10th, 1997 in Struga,
      (President--M. Polenakovic, Skopje). The III BANTAO congress was held in Belgrade
      from September 18th to 20th, 1998 (President--Lj. Djukanovic, Belgrade). The IV
      congress of BANTAO was held in Izmir from 14th to 16th November 1999 (President-
      A. Akcicek, Izmir). The V Congress of BANTAO was held in Thessaloniki from
      September 30th to October 3rd, 2001 (President--P. Stathakis, Athens). The VI
      Congress of BANTAO was held for the second time in Varna from 6th to 9th October
      2003 (President--D. Nenov, Varna). The VII congress of BANTAO was held from
      September 8th to 11th, 2005 in Ohrid, (President--M. Polenakovic, Skopje). The
      VIII BANTAO congress was held in Belgrade, 16-19 September 2007 (President--V.
      Nesic, Belgrade). The IX BANTAO congress was held in Antalya, 18-22 November 2009
      (President--A. Basci, Izmir). The X BANTAO congress was held from 13 to 15
      October 2011 in Chalkidiki (President--D. Tsakiris, Thessaloniki). The XI BANTAO
      congress is being held on 26-29 September 2013 in Timisoara (President--A.
      Schiller, Timisoara). At the VII BANTAO Congress for the first time a CME Course
      was organized by ERA/EDTA and ISN/COMGAN entitled "Frontiers in Nephrology" with
      seven distinguished speakers. Very important event in the existence of BANTAO is
      the appearance of the BANTAO journal in 2003. The BANTAO journal has been
      published biannually since 2003. In the past 10 years, 20 regular issues; 2
      supplements (Antalia and Chalkidiki congresses) have been published. Editors of
      the journal were as follows: 2003-2005--D. Nenov, Editor; 2005-2009--A. Basci,
      Editor; 2009--Goce Spasovski, Editor. Until now 332 papers have been published.
      The BANTAO journal is on EBSCO, DOAJ, SCOPUS. After the First Congress of BANTAO,
      F. Valderrabano, chairman of the EDTA--ERA Registry, at that time, wrote in
      Nephrology Dialysis Transplantation (1996) 11:740: "Nephrologists of the Balkan
      countries meet across political frontiers and war fronts--an example to
      politicians! BANTAO: a new European Medical Association overcomes Political
      obstacles." Despite the difficulties imposed by major events, such as devastating
      wars and catastrophic earthquakes in many countries of the Balkan Peninsula
      BANTAO has made considerable progress. The BANTAO Congress was established as the
      major scientific and institutional forum for Balkan nephrologists, with its own
      journal, indicating our will to communicate, to collaborate, to get to know each
      other and to share our difficulties. Now, we expect further successful work of
      BANTAO.

PMID- 24280894
TI  - Should we keep changing the diagnostic criteria for Behcet's disease?
AB  - In medicine, clinical acumen is used to achieve diagnosis, guide management and
      prevent disease. While for some diseases, diagnosis is reached with the
      assistance of objective tests, many conditions rely upon the use of clinical
      diagnostic criteria; Behcet's disease is one such case. In order to remain
      clinically relevant, as knowledge of a condition changes over time so too must
      its diagnostic criteria. Preferably, when new criteria for a disease are
      conceptualised it is through sound methodology, followed by a confirmation of
      accuracy by way of systematic validation and response to treatment. The most
      recently proposed revised International Criteria for Behcet's Disease for the
      diagnosis of Behcet's disease have been systematically validated and should
      replace the use of the clinically inferior International Study Group criteria,
      while not displacing the role of clinical judgement. Effort should now be
      invested in acquiring better understanding of the pathogenesis of the disease in
      the hope of developing a more objective test.

PMID- 24280895
TI  - A rapid and efficient method for primary culture of human adipose-derived stem
      cells.
AB  - Adipose tissue contains some populations, adipose-derived stem cells (ADSCs)
      which can differentiate into adipogenic, chondrogenic, osteogenic, myogenic, and
      endothelial cells. Furthermore, adipose tissue can be easily obtained in large
      quantities through a simple liposuction. ADSCs are thought to be an alternate
      source of autologous adult stem cells for cell-based therapy. However, it is time
      consuming and inefficient to harvest ADSCs by using a traditional collagenase
      digestion method. To meet the demand of large quantities of ADSCs in the basic
      and applied research of regenerative medicine, we developed a rapid and efficient
      method for isolation and culture of primary ADSCs. The results indicated that the
      ADSCs obtained with our method possessed strong abilities of proliferation and
      colony formation in vitro, and could keep low level of cell senescence with
      stable population doubling during long-term culture in vitro. Furthermore, these
      harvested ADSCs were capable to differentiate into osteogenic and adipogenic
      lineages in the specific induction medium. In addition, the results of flow
      cytometry analysis indicated that these ADSCs could positively express multiple
      CD markers, such as CD44, CD105, CD29, CD90, and CD13, and hardly expressed CD31,
      CD34, CD45, and CD106, which was homologous to the mesenchymal stem cells.
      Therefore, the ADSCs isolated with our method are consistent with previously
      reported characteristics of the ADSCs. This new method that we established in
      this study is an efficient tool to isolate and culture the stem cells from
      adipose tissue. 

PMID- 24280896
TI  - Epidemiologic factors and surgical outcomes in patients with nasal polyposis and
      asthma.
AB  - BACKGROUND/AIM: To evaluate the role of epidemiologic factors in surgical
      outcomes for patients with nasal polyposis (NP) and asthma. METHODS: Data was
      prospectively collected on patients who underwent endoscopic sinus surgery over a
      7-year period. Among patients with chronic rhinosinusitis (CRS) with NP and
      asthma, surgical outcomes were analyzed according to gender and race. RESULTS:
      Patients with NP and asthma had significantly higher Lund-Kennedy and SNOT-20
      scores--pre- and postoperatively--compared to CRS patients without NP or asthma.
      Both Caucasians and African-Americans in the CRS with NP/asthma group showed a
      statistically significant improvement at 6 months. Caucasians continued to have a
      significant improvement at 12 months, whereas African-Americans did not. There
      were no differences according to gender. CONCLUSION: In our patient population,
      African-Americans with NP and asthma had poorer outcomes following functional
      endoscopic sinus surgery.

PMID- 24280897
TI  - Triggers of key calcium signals during erythrocyte invasion by Plasmodium
      falciparum.
AB  - Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi
      step process mediated by specific interactions between host receptors and
      parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte
      binding-like (EBL) proteins are discharged from specialized organelles and used
      in early steps of invasion. Here we show that monoclonal antibodies against PfRH1
      (an RH) block merozoite invasion by specifically inhibiting calcium signalling in
      the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175
      (an EBL protein) have no effect on signalling. We further show that inhibition of
      this calcium signalling prevents EBA175 discharge and thereby formation of the
      junction between parasite and host cell. Our results indicate that PfRH1 has an
      initial sensing as well as signal transduction role that leads to the subsequent
      release of EBA175. They also provide new insights on how RH-host cell
      interactions lead to essential downstream signalling events in the parasite,
      suggesting new targets for malaria intervention.

PMID- 24280900
TI  - Estimating mortality in survivors of the acute coronary syndrome by the 4-drug
      score.
AB  - OBJECTIVE: Four drug classes, platelet inhibitors, beta-blockers, statins, and
      angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), have
      been shown to reduce mortality in clinical trials. We sought to evaluate whether
      the simple number of secondary prevention drugs at discharge is independently
      associated with 1-year mortality in acute coronary syndrome (ACS) patients.
      METHODS: We analyzed a prospective cohort study using data of all 5 Acute
      Coronary Syndrome Israeli Surveys (ACSIS) conducted between 2002 and 2010 in all
      Israeli cardiology departments. All 9,107 hospital survivors of ACS participated.
      RESULTS: A score from 1 to 4 discharge drugs was significantly associated with
      gradual decreasing rates of 1-year mortality (14.4, 9.0, 5.1, and 3.6%,
      respectively; p for trend <0.001). Only when the number of discharge drugs
      increased to 3-4 as a result of the intervention during hospitalization in
      patients initially admitted with 0-2 drugs, a significant multivariate-adjusted
      decrease in the hazard ratio (HR), independent of multiple baseline, admission
      presentation, and in-hospital course characteristics, was measured (HR, 0.66; 95%
      confidence interval, 0.50-0.87). CONCLUSION: The use of a higher number of
      secondary prevention drugs at discharge following ACS was associated with
      significantly lower mortality rates, particularly in patients with mono- or dual
      baseline therapy.

PMID- 24280898
TI  - How to understand the efficacy measurements for enterovirus type 71 vaccine?
AB  - The choice of endpoint was most important for an efficacy vaccine trial. The
      objective of this paper is to gear toward answering questions about the
      rationality and scientificity of the primary endpoints choosing, case capturing
      and diagnosis strategy in our recently reported EV71 vaccine efficacy phase 3
      trial. In order to obtain both high sensitivity and specificity in the case
      detecting, EV71-associated disease had been chosen as primary endpoint, a broad
      spectrum of clinical symptoms was surveyed, both the real-time RT-PCR and virus
      isolation were combined for the laboratory diagnosis, and serial specimens since
      disease onset were collected for assays. Though, the EV71 vaccine efficacy was
      well measured in the phase 3 trial, several potential factors could also have
      influences on the cases confirming. More evidence of EV71 vaccine efficacy will
      be demanded in post-marketing studies in the future. 

PMID- 24280901
TI  - ATM regulates Cdt1 stability during the unperturbed S phase to prevent re
      replication.
AB  - Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses,
      especially with regard to DNA double-strand breaks (DSBs). However, it appears
      that ATM can be activated not only by DSB, but also by some changes in chromatin
      architecture, suggesting potential ATM function in cell cycle control. Here, we
      found that ATM is involved in timely degradation of Cdt1, a critical replication
      licensing factor, during the unperturbed S phase. At least in certain cell types,
      degradation of p27(Kip1) was also impaired by ATM inhibition. The novel ATM
      function for Cdt1 regulation was dependent on its kinase activity and NBS1.
      Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S
      phase. ATM silencing induced partial reduction in levels of Skp2, a component of
      SCF(Skp2) ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2
      silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as
      reported previously, ATM silencing partially prevented Akt phosphorylation at
      Ser473, indicative of its activation, and Akt inhibition led to modest
      stabilization of Cdt1. Therefore, the ATM-Akt-SCF(Skp2) pathway may partly
      contribute to the novel ATM function. Finally, ATM inhibition rendered cells
      hypersensitive to induction of re-replication, indicating importance for
      maintenance of genome stability. 

PMID- 24280902
TI  - Pits confined in ultrathin cerium(IV) oxide for studying catalytic centers in
      carbon monoxide oxidation.
AB  - Finding ideal material models for studying the role of catalytic active sites
      remains a great challenge. Here we propose pits confined in an atomically thin
      sheet as a platform to evaluate carbon monoxide catalytic oxidation at various
      sites. The artificial three-atomic-layer thin cerium(IV) oxide sheet with
      approximately 20% pits occupancy possesses abundant pit-surrounding cerium sites
      having average coordination numbers of 4.6 as revealed by X-ray absorption
      spectroscopy. Density-functional calculations disclose that the four- and five
      fold coordinated pit-surrounding cerium sites assume their respective role in
      carbon monoxide adsorption and oxygen activation, which lowers the activation
      barrier and avoids catalytic poisoning. Moreover, the presence of coordination
      unsaturated cerium sites increases the carrier density and facilitates carbon
      monoxide diffusion along the two-dimensional conducting channels of surface pits.
      The atomically thin sheet with surface-confined pits exhibits lower apparent
      activation energy than the bulk material (61.7 versus 122.9 kJ mol(-1)), leading
      to reduced conversion temperature and enhanced carbon monoxide catalytic ability.

PMID- 24280903
TI  - Gender-associated differences in pulmonary rehabilitation outcomes in people with
      chronic obstructive pulmonary disease: a systematic review.
AB  - PURPOSE: Although there is substantial evidence to support the importance of
      pulmonary rehabilitation (PR) in the management of chronic obstructive pulmonary
      disease, there is less evidence for gender-associated differences in the response
      to PR. The purpose of this review was to systematically identify and synthesize
      the available literature on whether men and women with chronic obstructive
      pulmonary disease respond differently to PR. METHODS: A search of 4 electronic
      databases was conducted (January 1990 to May 2012) for all English language
      articles where the goal was to assess gender differences in outcomes after PR.
      RESULTS: Of the 116 articles retrieved, 11 were included. Five studies reported
      differences between men and women after PR, for the outcomes of dyspnea, health
      related quality of life, physical capacity, psychological and functional status,
      and coping strategies. Six studies reported no difference in response to PR for
      the same outcomes. No differences in study designs, study quality, participant
      characteristics, and type and duration of PR programs were observed between
      studies that showed gender differences and those that did not. CONCLUSION: There
      was insufficient evidence to support or refute gender-associated differences in
      PR outcomes. The impact of gender on the outcome of PR and how these differences
      may affect the delivery of PR programs remains to be defined.

PMID- 24280904
TI  - Deep breathing exercises performed 2 months following cardiac surgery: a
      randomized controlled trial.
AB  - PURPOSE: Postoperative breathing exercises are recommended to cardiac surgery
      patients. Instructions concerning how long patients should continue exercises
      after discharge vary, and the significance of treatment needs to be determined.
      Our aim was to assess the effects of home-based deep breathing exercises
      performed with a positive expiratory pressure device for 2 months following
      cardiac surgery. METHODS: The study design was a prospective, single-blinded,
      parallel-group, randomized trial. Patients performing breathing exercises 2
      months after cardiac surgery (n = 159) were compared with a control group (n =
      154) performing no breathing exercises after discharge. The intervention
      consisted of 30 slow deep breaths performed with a positive expiratory pressure
      device (10-15 cm H2O), 5 times a day, during the first 2 months after surgery.
      The outcomes were lung function measurements, oxygen saturation, thoracic
      excursion mobility, subjective perception of breathing and pain, patient
      perceived quality of recovery (40-Item Quality of Recovery score), health-related
      quality of life (36-Item Short Form Health Survey), and self-reported respiratory
      tract infection/pneumonia and antibiotic treatment. RESULTS: Two months
      postoperatively, the patients had significantly reduced lung function, with a
      mean decrease in forced expiratory volume in 1 second to 93 +/- 12% (P< .001) of
      preoperative values. Oxygenation had returned to preoperative values, and 5 of 8
      aspects in the 36-Item Short Form Health Survey were improved compared with
      preoperative values (P< .01). There were no significant differences between the
      groups in any of the measured outcomes. CONCLUSION: No significant differences in
      lung function, subjective perceptions, or quality of life were found between
      patients performing home-based deep breathing exercises and control patients 2
      months after cardiac surgery.

PMID- 24280905
TI  - Impact of an outpatient cardiac rehabilitation program on clinical and analytical
      variables in cardiovascular disease.
AB  - PURPOSE: The aim of the study was to determine the effect of lifestyle changes in
      patients participating in a cardiac rehabilitation program. METHODS: Patients
      with cardiovascular disease (N = 59) were enrolled in cardiac rehabilitation,
      which included nutritional and exercise interventions. All patients completed the
      program, but only 44 attended the reassessment after 12 months because of work
      reasons or lack of time or interest. RESULTS: Ergometry before and after cardiac
      rehabilitation showed significant differences in exercise tolerance time (5.2 +/-
      1.8 minutes vs 7.1 +/- 2.1 minutes; P< .001), metabolic equivalents (6.5 +/- 1.8
      vs 8.8 +/- 2.2; P< .001), and the Borg rating of perceived exertion scale (12 +/-
      1.8 points vs 13.7 +/- 1.6 points; P= .005). At the end of the intervention
      program, significant improvements were seen in body weight (82.6 +/- 15.2 kg vs
      80.8 +/- 14.3 kg; P< .001), waist circumference (100.3 +/- 12.4 cm vs 98.0 +/-
      11.0 cm; P= .002), and levels of fasting glucose (126.5 +/- 44.6 mmol/L vs 109.6
      +/- 24.8 mmol/L; P< .001), low-density lipoprotein cholesterol (2.7 +/- 0.9
      mmol/L vs 2.5 +/- 0.8 mmol/L; P= .033), and C-reactive protein (5.1 +/- 8.7
      MUg/mL vs 4.1 +/- 2.6 MUg/mL; P= .008), as well as in adherence to a healthy diet
      as estimated by the Trichopoulou questionnaire score (7.9 +/- 2.3 vs 10.6 +/-
      1.5; P< .001). Twelve months later, however, many of these benefits had either
      remained stable or worsened. CONCLUSIONS: Cardiac rehabilitation is an
      appropriate program for the improvement of clinical and analytical variables,
      such as functional capacity, carbohydrate and lipid metabolism, anthropometric
      measures, and diet. However, 12 months later, many of these benefits either
      remained stable or worsened.

PMID- 24280906
TI  - Prevalence and predictors of depression and anxiety among survivors of myocardial
      infarction due to spontaneous coronary artery dissection.
AB  - PURPOSE: Depression and anxiety after myocardial infarction (MI) are common and
      associated with increased morbidity and mortality. The epidemiology and
      pathophysiology of MI due to spontaneous coronary artery dissection (SCAD)
      differs substantially from atherosclerotic MI, and rates of mental health
      comorbidities after SCAD are unknown. We aimed to determine the prevalence and
      predictors of depression/anxiety in SCAD survivors. METHODS: In this cross
      sectional study, 158 SCAD survivors (97% women; mean age, 45.5 +/- 9.3 years)
      were screened for depression/anxiety via surveys, including the Patient Health
      Questionnaire Depression Scale (PHQ-9) and Generalized Anxiety Disorder 7-Item
      Scale (GAD-7), a mean 3.7 +/- 4.7 years after SCAD. Comorbidities and
      environmental, socioeconomic, and clinical cardiovascular characteristics were
      obtained from the surveys. RESULTS: Since their initial SCAD MI, 51 (33%)
      patients had received treatment with medications or counseling for depression and
      57 (37%) for anxiety. When surveyed, 46 (31.7%) were taking antidepressant or
      anxiolytic medications. Overall, mean PHQ-9 (4.1) and GAD-7 (4.7) scores
      suggested borderline mild depression/anxiety (normal range: 0-4). Younger age was
      associated with higher PHQ-9 (P = .04) and GAD-7 (P = .02) scores. The 19 (12%)
      patients with peripartum SCAD had higher mean PHQ-9 (6.7 vs 3.7; P < .0005) and
      GAD-7 (8.1 vs 4.3; P = .003) scores. Patients treated with percutaneous coronary
      intervention had lower PHQ-9 (1.5; P = .02) and GAD-7 (2.4; P = .004) scores.
      CONCLUSIONS: Symptoms of depression/anxiety are common in patients with MI due to
      SCAD, particularly younger women and those with peripartum SCAD. The PHQ-9 and
      GAD-7 assessments may detect depression/anxiety in SCAD survivors who do not self
      report these disorders, suggesting a role for routine screening in these
      patients.

PMID- 24280907
TI  - Giant cell tumors of the skull base: case series and current concepts.
AB  - OBJECTIVE: To study the clinical features, tumor characteristics and outcomes of
      giant cell tumors (GCTs) in the skull base based on long-term follow-up. We also
      report the largest series of GCTs in the temporal bone and the lateral skull
      base. MATERIALS AND METHODS: A retrospective study was conducted of all GCTs
      managed at the Gruppo Otologico, a quaternary referral skull base institute, in
      Italy from 1993 to 2013. The clinical features, investigations, surgical
      management and follow-up were recorded. The surgical approaches used were
      infratemporal fossa approach (ITFA) type B and D and middle cranial fossa (MCF)
      approaches. RESULTS AND OBSERVATIONS: A total of 7 patients with GCTs of the
      skull base were treated at our institution. The principal complaints were hearing
      loss reported in 6 (85.71%) patients, tinnitus in 5 (71.43%) and swelling in 3
      (42.9%). Pure-tone audiometry showed conductive hearing loss in 5 (71.43%)
      patients. High-resolution CT scan and MRI with gadolinium enhancement were done
      in all patients. Radiology showed involvement of the ITF and middle ear in 6
      (85.71%) patients each, temporomandibular joint in 4 (57.14%) patients, invasions
      of the squamous part of the temporal bone, mastoid, MCF and greater wing of
      sphenoid in 3 (42.9%) patients each and the petrous bone in 2 (28.6%) patients.
      ITFA type B was applied as an approach for tumor removal in 5 (71.43%) patients,
      including a case where an additional MCF approach was employed, and ITFA type D
      and the transmastoid approach were applied in 1 (14.3%) patient each. Total tumor
      removal and successful cure was achieved in 6 (85.71%) patients. Subtotal removal
      leading to recurrence and eventual mortality was the result in 1 (14.3%) patient.
      CONCLUSIONS: A thorough knowledge of the anatomy of the skull base and the
      various skull base approaches is necessary to tackle GCTs. ITFA type B and D
      combined with MCF approaches provide good exposure of the tumor with minimal
      postoperative sequelae and good locoregional control. Recurrence due to either
      subtotal removal or suboptimal treatment may have disastrous consequences for the
      patient.

PMID- 24280908
TI  - Degree of decrease in central retinal thickness predicts visual acuity response
      to intravitreal ranibizumab in diabetic macular edema.
AB  - PURPOSE: To characterize factors that may be associated with optimal or
      suboptimal response to ranibizumab intravitreal injections in diabetic macular
      edema (DME). METHODS: Fifty-nine eyes with DME treated with ranibizumab were
      included. All underwent best-corrected visual acuity (BCVA) assessment and
      optical coherence tomography (OCT) at baseline, 3 and 6 months. Central retinal
      thickness (CRT) was assessed at each visit, and OCT images were classified
      according to their morphological patterns. RESULTS: A mean BCVA increase of 4.78
      and 5.52 letters, and a CRT decrease of 80.25 and 106.12 um were found after 3
      and 6 months of treatment (p < 0.001). BCVA improvement was found to be dependent
      on baseline BCVA and the degree of CRT decrease. Twenty-six eyes (44%) showing a
      CRT decrease >= 20% improved BCVA by 10.3 +/- 13.0 letters, whereas 33 eyes (56%)
      with a CRT decrease <20% had BCVA improvement of 1.8 +/- 7.2 letters (odds ratio
      = 3.31). CONCLUSIONS: The degree of CRT decrease obtained by spectral-domain OCT
      identifies well the optimal responders to intravitreal ranibizumab and predicts
      BCVA improvement after treatment.

PMID- 24280909
TI  - Effects of surfactants on the photolysis of chlorothalonil on pepper (Capsicum
      annuum var. grossum Sendt).
AB  - Chlorothalonil is a widely used fungicide on pepper and other vegetables in
      China. The present study was aimed to evaluate effects of three different
      surfactants, sodium dodecyl sulfonate (SDS), Span-20, and cetyltrimethylammonium
      bromide (CTAB), on the photolysis of chlorothalonil on peppers under irradiation
      of either high-pressure mercury lamp (HPML) or sunlight inside and outside
      greenhouse. Results showed that both SDS and Span-20 at a low concentration
      exhibited a photosensitization effect on the photolysis of chlorothalonil under
      HPML. Such effect gradually decreased with increasing concentrations of either
      surfactant prior to photoquenching effects observed. In contrast, CTAB showed a
      photoquenching effect on chlorothalonil photolysis, which was gradually enhanced
      with an increasing CTAB concentration. SDS, Span-20, and CTAB had consistent
      effects on the photolysis of chlorothalonil under sunlight as those observed
      under HPML irradiation. The use of appropriate surfactants as pesticide additives
      at optimal concentrations could decrease the residue of pesticide in agricultural
      food and improve food safety.

PMID- 24280910
TI  - Self-recovering stimuli-responsive macrocycle-equipped supramolecular ionogels
      with unusual mechanical properties.
AB  - A chiral, crown-ether-functionalized bisurea gelator forms supramolecular gels in
      ionic liquids. The resulting ionogels show a remarkably high thermal stability
      with gel-sol transition temperatures (T(gs)) reaching more than 100  degrees C.
      The mechanical strength of these ionogels is surprisingly high and even
      comparable to that of cross-linked protein fibres. Furthermore, the ionogels
      exhibit rapid self-recovery properties after structural damage caused by
      deformation. Pseudorotaxanes form from the gelators' benzo[21]crown-7 ethers as
      the wheels and secondary ammonium ions as the axles despite the competition
      between that cation and the imidazolium ions of the ionic liquid for crown ether
      binding. Pseudorotaxane formation as an external chemical stimulus triggers the
      gel-sol transition of the ionogels.

PMID- 24280911
TI  - Cholesterol esterification as a mediator of proliferation of vascular smooth
      muscle cells and peripheral blood mononuclear cells during atherogenesis.
AB  - BACKGROUND/AIMS: We determined growth rates, cholesterol esterification and mRNA
      levels for caveolin-1 (Cav-1), neutral cholesterol esters hydrolase (n-CEH) and
      ATP-binding cassette transporter (ABCA-1), in quiescent and growth-stimulated
      peripheral blood mononuclear cells (PBMCs) and intimal vascular smooth muscle
      cells (VSMCs) from blood and primary atherosclerotic plaques, respectively. These
      cells were cultured in the presence or absence of the mTOR inhibitor 40-O-(2
      hydroxyethyl) rapamycin (RAD). METHODS: The rate of cell proliferation was
      determined by 3H-thymidine incorporation into DNA and that of lipid metabolism by
      utilizing 14C-acetate and 14C-oleate as precursors. Lipid deposit in the vascular
      cells was evaluated by Oil Red O staining and lipid mass by thin layer
      chromatography-linked enzymatic assay. RESULTS: Growth stimulation of PBMCs and
      VSMCs caused a rapid increase in intracellular cholesterol esterification and an
      accumulation of cholesterol esters (CEs) accompanied by a reduction of free
      cholesterol (FC) and Cav-1, ABCA-1 and n-CEH mRNAs. RAD reduced intracellular
      lipid accumulation in growth-stimulated cells and also increased expression of
      Cav-1, n-CEH and ABCA-1 genes. CONCLUSION: Collectively, these data provide
      evidence that the determination of CEs in PBMCs may be an easy prescreening test
      to identify subjects at risk for vascular proliferative disease and that FC, CE,
      Cav-1, n-CEH and ABCA-1 may be suitable targets for antiproliferative therapies.

PMID- 24280912
TI  - Present practice of thrombosis prophylaxis of radical prostatectomy in a European
      country: a Hungarian multicenter study.
AB  - Venous thromboembolism is a possible fatal complication after pelvic surgery.
      There is a lack of trials assessing the effect of prophylactic measures in
      urology. The aim of the study was to evaluate the practice of thrombosis
      prophylaxis in a Central European country. A questionnaire of performed radical
      prostatectomies, way of thrombosis prophylaxis and number of experienced
      thrombotic events was posted to all departments of urology in Hungary. With a
      response rate of 59%, 506 radical prostatectomies were reported. Low molecular
      weight heparin was administered by 100% of the departments. Graduated support
      stockings were applied by 37% of the patients. Early mobilization was the most
      common form of mechanic prophylaxis (57%). Thrombotic events were experienced in
      1.4%, 0.2% were fatal. The thrombosis prophylaxis of patients undergoing radical
      prostatectomy is not unified. Due to the potential mortality of thrombotic
      complications it should be evaluated and prophylaxis should be recommended in
      urological guidelines.

PMID- 24280913
TI  - Differences between HIV-Infected men and women in antiretroviral therapy outcomes
      - six African countries, 2004-2012.
AB  - Evaluation of differences between human immunodeficiency virus (HIV)-infected men
      and women in antiretroviral therapy (ART) enrollment characteristics and outcomes
      might identify opportunities to improve ART program patient outcomes and
      prevention impact. During September 2008-February 2012, retrospective cohort
      studies to estimate attrition of enrollees (i.e., from death, stopping ART, or
      loss to follow-up) at 6-month intervals after ART initiation were completed among
      samples of adult men and women (defined as aged >=15 years or aged >=18 years)
      who initiated ART during 2004-2010 in six African countries: Cote d'Ivoire in
      western Africa; Swaziland, Mozambique, and Zambia in southern Africa; and Uganda
      and Tanzania in eastern Africa. Records for 13,175 ART enrollees were analyzed;
      sample sizes among the six countries ranged from 1,457 to 3,682. In each country,
      women comprised 61%-67% of ART enrollees. Median CD4 count range was 119-141
      cells/uL for men and 137-161 cells/uL for women. Compared with women, a greater
      percentage of men initiated ART who had World Health Organization (WHO) HIV stage
      IV disease. In cohorts from western Africa and southern Africa, the risk for
      attrition was 15%-26% lower among women compared with men in multivariable
      analysis. However, in eastern Africa, differences between men and women in risk
      for attrition were not statistically significant. Research to identify country
      specific causes for increased attrition and delayed initiation of care among men
      could identify strategies to improve ART program outcomes among men, which might
      contribute to prevention of new HIV infections in female partners. 

PMID- 24280914
TI  - Voluntary medical male circumcision - southern and eastern Africa, 2010-2012.
AB  - Sub-Saharan Africa bears the greatest global burden of human immunodeficiency
      virus (HIV) infection; 70% (25.0 million) of all persons living with HIV reside
      in this region. Voluntary medical male circumcision (VMMC) has been shown to
      reduce the risk for heterosexually acquired HIV among men by approximately 60% in
      three randomized controlled trials. Further studies found that the protection
      from HIV acquisition conferred by VMMC was sustained for 6 years following
      surgery. In 2007, the World Health Organization (WHO) and Joint United Nations
      Programme on HIV/AIDS (UNAIDS) recommended that 14 countries with generalized HIV
      epidemics (i.e., where >1% of the population is HIV-positive) and low male
      circumcision prevalence prioritize scale-up of VMMC for HIV prevention. On
      December 1, 2011 (World AIDS Day), funding through the President's Emergency Plan
      for AIDS Relief (PEPFAR) was announced to support >4.7 million VMMCs over the
      next 2 years. This report presents the results of VMMC scale-up in nine countries
      where national ministries of health and CDC are implementing VMMC services for
      HIV prevention: Botswana, Kenya, Malawi, Mozambique, Namibia, South Africa,
      Tanzania, Uganda, and Zambia. During October 2009-September 2012, a total of
      1,924,792 VMMCs were performed in 14 countries using PEPFAR funding provided
      through U.S. government agencies; of this total, 1,020,424 were conducted at
      approximately 1,600 CDC-supported VMMC sites: 137,096 VMMCs in 2010, 347,724 in
      2011, and 535,604 in 2012. Continued program monitoring and quality assurance
      activities are required to ensure that CDC-supported country programs meet World
      AIDS Day targets for VMMC.

PMID- 24280915
TI  - HIV testing and risk behaviors among gay, bisexual, and other men who have sex
      with men - United States.
AB  - The burden of human immunodeficiency virus (HIV) is high among gay, bisexual, and
      other men who have sex with men (MSM). High HIV prevalence, lack of awareness of
      HIV-positive status, unprotected anal sex, and increased viral load among HIV
      positive MSM not on antiretroviral treatment contribute substantially to new
      infections among this population. CDC analyzed data from the National HIV
      Surveillance System (NHSS) to estimate the percentage of HIV diagnoses among MSM
      by area of residence and data from the National HIV Behavioral Surveillance
      System (NHBS) to estimate unprotected anal sex in the past 12 months among MSM in
      2005, 2008, and 2011; unprotected discordant anal sex at last sex (i.e., with a
      partner of opposite or unknown HIV status) in 2008 and 2011; and HIV testing
      history and the percentage HIV-positive but unaware of their HIV status by the
      time since their last HIV test in 2011. This report describes the results of
      these analyses. In all but two states, the majority of new HIV diagnoses were
      among MSM in 2011. Unprotected anal sex at least once in the past 12 months
      increased from 48% in 2005 to 57% in 2011 (p<0.001). The percentage engaging in
      unprotected discordant anal sex was 13% in 2008 and 2011. In 2011, 33% of HIV
      positive but unaware MSM reported unprotected discordant anal sex. Among MSM with
      negative or unknown HIV status, 67% had an HIV test in the past 12 months. Among
      those tested recently, the percentage HIV-positive but unaware of their infection
      was 4%, 5%, and 7% among those tested in the past <=3, 4-6, and 7-12 months,
      respectively. Expanded efforts are needed to reduce HIV risk behaviors and to
      promote at least annual HIV testing among MSM. 

PMID- 24280916
TI  - Tularemia - United States, 2001-2010.
AB  - Tularemia is a rare but potentially serious bacterial zoonosis that has been
      reported from all U.S. states except Hawaii. The etiologic agent, Francisella
      tularensis, is highly infectious and can be transmitted through arthropod bites,
      direct contact with infected animal tissue, inhalation of contaminated aerosols,
      and ingestion of contaminated food or water. F. tularensis has been designated a
      Tier 1 select agent because it meets several criteria, including low infectious
      dose, ability to infect via aerosol, and a history of being developed as a
      bioweapon (2). This report summarizes tularemia cases reported to CDC during 2001
      2010 via the National Notifiable Diseases Surveillance System (NNDSS) and
      compares the epidemiology of these cases with those reported during the preceding
      decade. During 2001-2010, a total of 1,208 cases were reported (median: 126.5
      cases per year; range: 90-154). Incidence was highest among children aged 5-9
      years and men aged >55 years. Clinicians and public health practitioners should
      be familiar with the current epidemiology and clinical features of tularemia to
      identify and adequately treat individual cases and recognize unusual patterns
      that might signal an outbreak or bioterrorism event. 

PMID- 24280918
TI  - Caldicott report reviewed.

PMID- 24280917
TI  - Very high blood lead levels among adults - United States, 2002-2011.
AB  - Over the past several decades there has been a remarkable reduction in
      environmental sources of lead, improved protection from occupational lead
      exposure, and an overall decreasing trend in the prevalence of elevated blood
      lead levels (BLLs) in U.S. adults. As a result, the U.S. national BLL geometric
      mean among adults was 1.2 ug/dL during 2009-2010. Nonetheless, lead exposures
      continue to occur at unacceptable levels. Current research continues to find that
      BLLs previously considered harmless can have harmful effects in adults, such as
      decreased renal function and increased risk for hypertension and essential tremor
      at BLLs <10 ug/dL. CDC has designated 10 ug/dL as the reference BLL for adults;
      levels >=10 ug/dL are considered elevated. CDC's Adult Blood Lead Epidemiology
      and Surveillance (ABLES) program tracks elevated BLLs among adults in the United
      States. In contrast to the CDC reference level, prevailing Occupational Safety
      and Health Administration (OSHA) lead standards allow workers removed from lead
      exposure to return to lead work when their BLL falls below 40 ug/dL. During 2002
      2011, ABLES identified 11,536 adults with very high BLLs (>=40 ug/dL). Persistent
      very high BLLs (>=40 ug/dL in >=2 years) were found among 2,210 (19%) of these
      adults. Occupational exposures accounted for 7,076 adults with very high BLLs
      (91% of adults with known exposure source) and 1,496 adults with persistent very
      high BLLs. Adverse health effects associated with very high BLLs underscore the
      need for increased efforts to prevent lead exposure at workplaces and in
      communities. 

PMID- 24280919
TI  - Influenza: an outbreak in a UK respiratory centre.

PMID- 24280920
TI  - Student nurses' intention to get the influenza vaccine.
AB  - INTRODUCTION: There is no national or international recommendation for nursing
      students to receive the influenza vaccine. Nurses are among the group of health
      professionals who traditionally have a low uptake of the vaccine and who arguably
      have the closest contact with patients. AIM: To investigate the uptake of
      influenza vaccination among student nurses, explore reasons for either declining
      or receiving it in the past, and establish if and to what extent the theory of
      planned behaviour (TPB) can explain vaccination behaviour. METHODS: A
      quantitative, descriptive, correlational design was used. Data were collected
      with a researcher-developed questionnaire; 131 student nurses participated.
      Ethical approval was gained. RESULTS: 79% (n=104) had never received the vaccine.
      The most common reason was 'I don't need it as I rarely get ill'. Low mean
      'intention' scores indicated that students were unlikely to get the vaccine once
      qualified. Past behaviour was significantly associated with future intentions.
      The TPB explained 41.9% of the variance in intention. Attitude emerged as the
      greatest predictor. CONCLUSION: Student nurses do not have strong intentions to
      get the vaccine. Results serve to guide future educational and occupational
      health initiatives, which would benefit from a framework based on TPB.

PMID- 24280921
TI  - Improving influenza vaccine uptake in frontline staff.
AB  - Influenza is a highly contagious upper respiratory tract disease causing
      significant morbidity and mortality among high-risk groups. Immunization of
      frontline healthcare workers (HCWs) in the NHS is thought to be beneficial in
      reducing subclinical infection, staff sickness absences and protects patients.
      Each year Public Health England launches the Seasonal Flu Campaign to help reduce
      influenza transmission by reinforcing the message that it is vital that frontline
      HCWs get vaccinated. Public Health produces figures on frontline workers who have
      been vaccinated annually. The 2011/2012 campaign showed uptake figures of the
      influenza vaccine was averaging 44.6% nationally. The efforts of an NHS trust to
      increase staff uptake of the annual seasonal flu vaccination programme has been
      highly commended as it achieved an impressive 68.7% uptake against a target of
      70%. This article shows how the trust worked hard to improve uptake on flu
      vaccinations for HCWs during the 2012/2013 flu season. Recognised as a Top
      Improver by NHS Employers (2013) for vaccination uptake, the Trust identifies how
      measures can be adopted to improve vaccination rates and what barriers can
      prevent total compliance. High rates of HCW vaccination can benefit staff,
      patients and the communities within which they work and live. 

PMID- 24280922
TI  - Solution-focused approach therapy for mental health nursing students.
AB  - Solution-focused therapy is a model of therapy that builds on the client's
      strengths, is future-focused and can be generally offered as a brief
      intervention. It can be used across multiple clinical settings and is not limited
      to being useful for clients accessing mental health services. Learning the
      underlying principles and developing a foundation level of skill in the approach
      was found to be achievable in an undergraduate nursing course, with students
      reporting an increase in their knowledge of the model and confidence in basic
      therapeutic skills in just one day of training. In this paper, we introduce the
      solution-focused approach in relation to nursing practice. We describe the
      template used for the training day offered to undergraduate mental health nurses.
      Students reported that this method of learning a therapeutic approach was helpful
      and increased both their knowledge and skill base. 

PMID- 24280923
TI  - Preoperative antiseptic skin preparations and reducing SSI.
AB  - Surgical site infection (SSI) can affect the quality of care and increase the
      morbidity and mortality rate in after-surgical procedure. The use of an
      antiseptic skin preparation agent before the procedure can reduce the pathogens
      in the skin surface around the incision. Indicating the type of skin antiseptic
      preparation could prevent the infection and contamination of the wound. The most
      commonly used types of skin preparations are chlorhexidine and povidone iodine.
      However, the antiseptic solutions of both agents are strengthened with alcohol to
      prevent postoperative wound infection. The aim of this paper is to identify the
      best antiseptic agent in terms of skin preparation by evaluating the evidence in
      the literature. The factors associated with choosing the antiseptic skin agent,
      such as patients' allergies, skin condition and environmental risk, are also
      taken into account. This review suggests that cholorhexdine with alcohol may be
      the most effective in terms of reducing SSI. 

PMID- 24280924
TI  - Pain management in Jordan: nursing students' knowledge and attitude.
AB  - Pain management requires knowledgeable and trained nurses. Because nursing
      students are the nurses of the future, it is important to ensure that students
      receive adequate education about pain management in nursing schools. The purpose
      of this study is to evaluate nursing students' knowledge and attitudes regarding
      pain management. A cross-sectional survey was used. The sample comprised 144
      students from three nursing colleges in Jordan. Sixty-one percent were female and
      the average age was 21.6 years (SD 1.7). The students' Knowledge and Attitudes
      Survey Regarding Pain was used. The rate of correct answers ranged from 11.1% to
      64%. Students showed a low level of knowledge regarding pain management-the
      average score was just 16 (SD 5.11) out of 40. Students were weak in their
      knowledge of pain medications pharmacology (actions and side effects). Less than
      half of students (47.9%) recognised that pain may be present, even when vital
      signs are normal and facial expressions relaxed. Finally, students showed
      negative attitudes towards pain management, believing that patients should
      tolerate pain as much as they can before receiving opioids; almost half (48%) of
      students agreed that patients' pain could be managed with placebo rather than
      medication. In conclusion, Jordanian nursing students showed lower levels of pain
      knowledge compared with other nursing students around the world. This study
      underlines the need to include pain-management courses throughout undergraduate
      nursing curricula in Jordan. 

PMID- 24280925
TI  - Using exercise to improve quality of life for people with heart failure.
AB  - In the current economic climate within the NHS, behavioural-change interventions
      in chronic disease such as exercise programmes will be time-limited within acute
      hospital facilities. The challenge is to deliver cost-effective, participatory,
      population-specific health interventions that result in measurable benefits.
      METHODOLOGY: A mixed-methods study was undertaken to assess the benefits of
      participation in a structured exercise programme for patients with heart failure.
      Primary outcomes were improvements in functional capacity and quality of life.
      Secondary outcome measures related to patient satisfaction and sustainability of
      the intervention post study. RESULTS: Overall significant improvements were not
      found in quality of life or functional capacity; some participants demonstrated
      significant improvements with others showing minor improvement or no improvement
      in one or both domains. CONCLUSIONS: Anecdotal evidence of perceived benefit was
      expressed in participant satisfaction responses. Secondary outcomes were met in
      relation to sustainability with commissioning of hospital- and community-based
      programmes on completion of the study.

PMID- 24280926
TI  - Making the most of being a student nurse.

PMID- 24280927
TI  - Lung transplantation assessment in a patient with COPD: a case study.
AB  - This article focuses on the lung transplant assessment process for a patient with
      chronic obstructive pulmonary disease (COPD). It explains the investigations
      undertaken and their relevance in the context of transplantation. For a patient
      to be accepted onto the lung transplant waiting list, it is important to
      establish that their lung disease is severe enough to warrant transplantation,
      while ensuring that the patient is well enough to undergo the procedure with the
      potential for a good subsequent quality of life. The article also explores the
      importance of supportive care, symptom management and psychosocial assessment in
      potential lung transplant recipients. 

PMID- 24280928
TI  - Good nursing does not come cheap.

PMID- 24280929
TI  - Making time to care by making social care fair.

PMID- 24280930
TI  - Is the quality of care in England getting better?

PMID- 24280931
TI  - Clinical supervision: from staff nurse to nurse consultant. Part 9: models of
      implementation.

PMID- 24280932
TI  - Health care starts with the heart.

PMID- 24280933
TI  - Systemic inflammatory response syndrome (SIRS): where did it come from and is it
      still relevant today?
AB  - The concept of a systemic inflammatory response syndrome (SIRS) to describe the
      complex pathophysiologic response to an insult such as infection, trauma, burns,
      pancreatitis, or a variety of other injuries came from a 1991 consensus
      conference charged with the task of developing an easy-to-apply set of clinical
      parameters to aid in the early identification of potential candidates to enter
      into clinical trials to evaluate new treatments for sepsis. There was recognition
      that a diverse group of injuries produced a common inflammatory response in the
      host and provided attractive targets for new anti-inflammatory molecules designed
      to prevent further propagation and/or provide specific treatment. Effective
      application of these new anti-inflammatory strategies necessitated identification
      of early clinical markers that could be assessed in real-time and were likely to
      define a population of patients that would have a beneficial response to the
      targeted intervention. It was felt that early clinical manifestations might be
      more readily available to clinicians than more sophisticated and specific assays
      for inflammatory substances that were systemically released by the network of
      injurious inflammatory events. Therefore, the early definition of a systemic
      inflammatory response syndrome (SIRS) was built upon a foundation of basic
      clinical and laboratory abnormalities that were readily available in almost all
      clinical settings. With further refinement, it was hoped, that this definition
      would have a high degree of sensitivity, coupled with a reasonable degree of
      specificity. This manuscript reviews the derivation, application, utilization,
      potential benefits, and speculation regarding the future of the SIRS definition. 

PMID- 24280934
TI  - Anti-apoptotic pathways in bone marrow and megakaryocytes in myeloproliferative
      neoplasia.
AB  - OBJECTIVE: Proliferative activity contributes to bone marrow cellularity in
      myeloproliferative neoplasia (MPN). Megakaryocytes are the most important cells
      in MPN bone marrow pathology. JAK2(V617F) mutation constitutively activates JAK2,
      pErk (phosphorylating extracellular signal-regulated kinase) and PI3K
      (phosphatidylinositol 3-kinase)-Akt signaling. Erk is involved in megakaryocyte
      differentiation, PI3K-Akt inhibits megakaryocyte apoptosis via Bcl-xL and two
      downstream effectors (p70S6k and Bnip3). Immunohistochemic expression of
      phosphorylated Erk, Akt, p70S6k and Bnip3 was studied along with microvessel
      density (MVD) in MPN bone marrow and megakaryocytes. METHODS: 36 essential
      thrombocythemia (ET), 25 polycythemia vera and 45 primary myelofibrosis patients
      were analyzed for pErk, pAkt, Bnip3, p70S6k and MVD expression by immunostaining
      bone marrow biopsy sections followed by automated image analysis. JAK2(V617F) was
      analyzed through real-time PCR in blood samples. RESULTS: pErk and pAkt were
      significantly higher expressed in MPN megakaryocytes, mainly in ET patients,
      compared to controls. Bnip3 was higher expressed in bone marrow of control
      patients and in MPN megakaryocytes. Mainly in ET patients, MPN megakaryocytes
      showed higher p70S6k expression compared to controls. CONCLUSION: Increased bone
      marrow cellularity in MPN patients might be influenced by increased pErk, pAkt
      and decreased Bnip3 expression. A dominant role for megakaryocytes in ET patients
      was shown. Increased amounts of megakaryocytes in MPN patients can be due to
      increased pAkt and p70S6k.

PMID- 24280935
TI  - Interleukin-23 is sufficient to induce rapid de novo gut tumorigenesis,
      independent of carcinogens, through activation of innate lymphoid cells.
AB  - Chronic inflammation has been associated with increased risk for developing
      gastrointestinal cancer. Interleukin-23 (IL-23) receptor signaling has been
      correlated with inflammatory bowel disease pathogenesis, as well as promotion of
      tumor growth. However, little is known about the relative potential for IL-23
      directed causality in gut tumorigenesis. We report that IL-23 transgene
      expression was sufficient to induce rapid (3-4 weeks) de novo development of
      intestinal adenomas with 100% incidence. Initiation of tumorigenesis was
      independent of exogenous carcinogens, Helicobacter colonization, or pre-existing
      tumor-suppressor gene mutations. Tumorigenesis was mediated by Thy1(+)IL-23R(+)
      innate lymphoid cells (ILC3), in part, through IL-17 responses as tumor
      development was inhibited in RAG(-/-) * IL-17(-/-) double knockout mice.
      Remarkably, IL-23 initiation of tumorigenesis by resident ILCs consistently
      occurred before recruitment of conspicuous inflammatory infiltrates. Our results
      reveal an explicit role for IL-23-mediated initiation of gut tumorigenesis and
      implicate a key role for IL-23R(+) ILC3 in the absence of overt cellular
      infiltrate recruitment. 

PMID- 24280936
TI  - NLRC4 expression in intestinal epithelial cells mediates protection against an
      enteric pathogen.
AB  - The inflammasomes have an important role in connecting the detection of
      endogenous and microbial danger signals to caspase-1 activation and induction of
      protective immune responses. NLRC4 is a cytosolic NOD (nucleotide binding and
      oligomerization domain)-like receptor (NLR) that can trigger inflammasome
      formation in response to bacterial flagellin, an immunodominant antigen in the
      intestine. To characterize the role of NLRC4 in bacterially triggered intestinal
      inflammation, we used the murine pathogen Citrobacter rodentium, an
      extracellular, attaching/effacing bacterium similar to enterohemorrhagic
      Escherichia coli and enteropathogenic E. coli. Following infection with C.
      rodentium, we found that Nlrc4(-/-) mice developed more severe weight loss,
      increased bacterial colonization levels, and exacerbated intestinal inflammation
      compared with wild-type counterparts. Nlrc4(-/-) mice mounted robust adaptive
      immune responses but were unable to control early colonization by C. rodentium,
      suggesting that a defect in innate immunity was responsible. Experiments using
      bone marrow (BM) chimeras revealed that the protective effects of NLRC4 were
      dependent on its expression in non-hematopoietic cells, and quantitative PCR (Q
      PCR) analyses revealed that NLRC4 was highly expressed in epithelial crypts but
      not in intestinal stroma. Thus, early NLRC4 sensing in intestinal epithelial
      cells regulates colonization by an extracellular bacterial pathogen and limits
      subsequent intestinal damage. 

PMID- 24280937
TI  - Nlrp3 activation in the intestinal epithelium protects against a mucosal
      pathogen.
AB  - Polymorphisms in the intracellular pattern recognition receptor gene NLRP3 (NLR
      family, pyrin domain containing 3) have been associated with susceptibility to
      Crohn's disease, a type of inflammatory bowel disease. Following tissue damage or
      infection, NLRP3 triggers the formation of inflammasomes, containing NLRP3, ASC
      (apoptosis-associated speck-like protein containing a CARD domain), and caspase
      1, that mediate secretion of interleukin (IL)-1beta and IL-18. However, the
      precise role of NLRP3 inflammasomes in mucosal inflammation and barrier
      protection remains unclear. Here we show that upon infection with the
      attaching/effacing intestinal pathogen Citrobacter rodentium, Nlrp3(-/-) and Asc(
      /-) mice displayed increased bacterial colonization and dispersion, more severe
      weight loss, and exacerbated intestinal inflammation. Analyses of irradiation
      bone marrow chimeras revealed that protection from disease was mediated through
      Nlrp3 activation in nonhematopoietic cells and was initiated very early after
      infection. Thus, early activation of Nlrp3 in intestinal epithelial cells limits
      pathogen colonization and prevents subsequent pathology, potentially providing a
      functional link between NLRP3 polymorphisms and susceptibility to inflammatory
      bowel disease. 

PMID- 24280938
TI  - Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances
      bacterial clearance from the lung.
AB  - Phagocytes not only coordinate acute inflammation and host defense at mucosal
      sites, but also contribute to tissue damage. Respiratory infection causes a
      globally significant disease burden and frequently progresses to acute
      respiratory distress syndrome, a devastating inflammatory condition characterized
      by neutrophil recruitment and accumulation of protein-rich edema fluid causing
      impaired lung function. We hypothesized that targeting the intracellular protein
      myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519)
      or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of
      established inflammation, but without detriment to bacterial clearance. Mcl-1
      loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis
      nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant
      inflammation was modelled in mice by either endotoxin or bacteria (Escherichia
      coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro
      resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and
      improved organ dysfunction with enhanced alveolar-capillary barrier integrity.
      Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil
      apoptosis and delayed resolution of endotoxin-mediated lung inflammation.
      Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated
      resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced
      bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates
      inflammation resolution without detriment to host defense against bacteria, and
      represents a target for treating infection-associated inflammation.

PMID- 24280939
TI  - Bile duct lesions associated with turnip (Brassica rapa) photosensitization
      compared with those due to sporidesmin toxicosis in dairy cows.
AB  - Cattle grazing turnips or other brassica forage crops occasionally develop
      hepatogenous photosensitization. In New Zealand, cases of bovine
      photosensitization associated with such crops frequently occur during late summer
      and fall, and this coincides with the facial eczema (sporidesmin toxicosis)
      "season." Clinical chemistry findings in acute photosensitization cases
      associated with both brassica and facial eczema include marked serum elevations
      in gamma-glutamyl transferase and glutamate dehydrogenase activities. Distinctive
      bile duct lesions of "subacute" turnip photosensitization in 2 cows, comprising
      microscopic cholangiectasis with concentric periductal fibrosis of small bile
      ducts, and a spectrum of changes from bile duct necrosis progressing to
      obliterative sclerosis are described. These bile duct lesions are compared with
      those in 3 cases of "subacute" facial eczema in adult cows, where medium-sized
      and larger ducts tend to be involved and bile duct hyperplasia and portal
      fibrosis are more prominent, often leading to bridging between neighboring portal
      triads. 

PMID- 24280940
TI  - Diagnostic immunohistochemistry of canine and feline intracalvarial tumors in the
      age of brain biopsies.
AB  - The focus of immunohistochemistry as applied to nervous system tumors is in
      identifying the neoplasm present and evaluating margins between normal and
      neoplastic tissue. Although not always utilized by specialists in neuropathology,
      immunohistochemistry remains useful to resolve concerns about the differentiation
      and rate of tumor growth. The aims of this review are to discuss the utility of
      immunohistochemical reagents currently used in diagnosis of canine and feline
      intracalvarial tumors, to indicate the applicability of some tests currently used
      in human nervous system tumors for domestic species, and to evaluate a few less
      commonly used reagents. A panel of biomarkers is usually needed to confirm a
      diagnosis, with groups of reagents for leptomeningeal, intraparenchymal, and
      ventricular neoplasms. In the future, signature genetic alterations found among
      feline and canine brain tumors--as correlated prospectively with diagnosis, rate
      of enlargement, or response to treatment--may result in new immunohistochemical
      reagents to simplify the task of diagnosis. Prospective studies determining the
      type and proportion of stem cell marker expression on patient longevity are
      likely to be fruitful and suggest new therapies. Due to increased frequency of
      biopsy or partial resection of tumors from the living patient, biomarkers are
      needed to serve as accurate prognostic indicators and assist in determining the
      efficacy of developing therapeutic options in nervous system tumors of dogs and
      cats.

PMID- 24280941
TI  - Transmission of systemic AA amyloidosis in animals.
AB  - Amyloidoses are a group of protein-misfolding disorders that are characterized by
      the deposition of amyloid fibrils in organs and/or tissues. In reactive amyloid A
      (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and
      wild animals, and humans that experience chronic inflammation. AA amyloid fibrils
      are abnormal beta-sheet-rich forms of the serum precursor SAA, with
      conformational changes that promote fibril formation. Extracellular deposition of
      amyloid fibrils causes disease in affected animals. Recent findings suggest that
      AA amyloidosis could be transmissible. Similar to the pathogenesis of
      transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process
      that may lead to development of AA amyloidosis. We review studies of possible
      transmission in bovine, avian, mouse, and cheetah AA amyloidosis. 

PMID- 24280942
TI  - Histologic characterization of the cat middle ear: in sickness and in health.
AB  - The purpose of this study was to establish microscopic normal in the middle ear
      of the cat while concurrently characterizing gross and microscopic lesions
      reflecting spontaneous otitis media. Both ears from 50 cats were examined grossly
      and processed for histologic examination of the external, middle, and internal
      ear on a single slide. Gross lesions of the middle ear were present in 14 of 100
      (14%) and included turbid fluid, frank pus, hemorrhage, and fibrous thickening of
      the auricular mucoperiosteum. Histologically, 48 of 100 (48%) ears had evidence
      of ongoing or previous inflammatory middle ear disease, including proteinaceous
      fluid; vascular ectasia; expansion of the auricular mucoperiosteum by
      neutrophils, lymphocytes, and macrophages; cholesterol clefts; hemorrhage;
      fibrin; granulation tissue; membranous pseudo-glands; fibrosis; proliferation
      and/or osteolysis of the tympanic and septum bullae. Histologic lesions were
      identified in 34 of 100 ears (34%) lacking gross evidence of disease. Ears were
      classified histologically as either normal (52/100 [52%]) or diseased (48/100
      [48%]). Diseased ears were further classified as mild to moderate (37/100 [37%])
      or severely (11/100 [11%]) affected. Internal ear involvement was present in 11
      of 100 (11%) ears. Histologic evidence of middle ear disease in cats is far
      greater than gross lesions or clinical literature suggests; further investigation
      and correlation of clinical and histologic disease are warranted. With minimal
      additional preparation, diagnostic specimens may be readily prepared and
      evaluated for this integral sensing organ. 

PMID- 24280944
TI  - A porous metal-metalloporphyrin framework featuring high-density active sites for
      chemical fixation of CO2 under ambient conditions.
AB  - Self-assembly of the custom-designed octatopic porphyrin ligand of tetrakis(3,5
      dicarboxybiphenyl)porphine with the in situ generated Cu2(CO2)4 paddlewheel
      moieties afforded a porous metal-metalloporphyrin framework, MMPF-9, which
      features a high density of Cu(II) sites confined within nanoscopic channels and
      demonstrates excellent performances as a heterogeneous Lewis-acid catalyst for
      chemical fixation of CO2 to form carbonates at room temperature under 1 atm
      pressure.

PMID- 24280943
TI  - Design of a simplified histopathologic model for gastrointestinal inflammation in
      dogs.
AB  - Significant interobserver variability in the diagnostic interpretation of
      endoscopic gastrointestinal (GI) specimens exists even with the use of World
      Small Animal Veterinary Association (WSAVA) standardization criteria. Chi-square
      analyses compared the extent of pathologists' agreement for microarchitectural
      features of inflammation in endoscopic specimens obtained from 253 animals of the
      original WSAVA study. Patterns of agreement between pathologists were classified
      as broad (3/4 pathologists agreed), dichotomous (2/4 pathologists agreed), or
      divergent (no agreement between pathologists). The simplified model for GI
      inflammation was based on those parameters for which the pathologists had either
      broad or minimally divergent opinions of histopathologic significance. In this
      model, the parameters chosen were as follows: gastric parameters (intraepithelial
      lymphocytes [IELs], lamina propria [LP] infiltrates, and mucosal fibrosis),
      duodenal parameters (villus atrophy, epithelial injury, IELs, crypt changes, and
      LP infiltrates), and colonic parameters (epithelial injury, crypt dilation,
      fibrosis, LP infiltrates, and goblet cell depletion). Preliminary data using this
      simplified model showed excellent correlation between pathologists in defining
      the presence and extent of GI inflammation in dogs. 

PMID- 24280946
TI  - Application of the defect area in transcatheter closure of atrial septal defect.
AB  - OBJECTIVES: It was our aim to evaluate whether the defect area plays a crucial
      role in successful device closure of atrial septal defects (ASDs). METHODS: The
      long and short diameters of the defect were measured on en-face images. The
      defect area was then measured by planimetry. The device size compared to the
      defect length and defect area was analyzed in each group. RESULTS: There were 22
      patients in the circular group and 45 patients in the noncircular group. The
      defect area did not differ between the groups (201.6 +/- 107.1 vs. 245.6 +/-
      127.6 mm(2)). Although the length between the device size and the long diameter
      differed between the groups (3.4 +/- 2.0 vs. 0.8 +/- 3.7 mm; p = 0.003), there
      was no difference in the ratio of the device area compared to the defect area,
      which was constant even in the noncircular defect (1.73 +/- 0.41 vs. 1.72 +/-
      0.53 mm(2); p = 0.947). The device size was positively correlated with the defect
      area (p < 0.01). CONCLUSION: The defect area measured by planimetry on en-face
      images might be useful in selecting the device size for transcatheter closure of
      ASDs.

PMID- 24280947
TI  - Effect of magnesium therapy on nocturnal leg cramps: a systematic review of
      randomized controlled trials with meta-analysis using simulations.
AB  - BACKGROUND AND OBJECTIVE: Nocturnal leg cramps (NLC) are common in primary care
      and may cause severe pain and sleep disturbance. We systematically reviewed the
      effectiveness of magnesium in treating NLC and the side-effect profile of
      magnesium compared to placebo. METHODS: We searched Medline, Embase, Cochrane
      Library, ClinicalTrials.gov, the International Standard Randomised Controlled
      Trial Number and the International Clinical Trials Registry Platform registries
      until August 2012. All randomized controlled trials (RCTs) comparing magnesium
      therapy for NLC in adults with any other comparator were eligible. Two
      investigators independently selected, extracted data from and rated the risk of
      bias of relevant studies. To compensate for the heterogeneity in outcome
      measures, simulations were used to summarize the data. RESULTS: Seven RCTs were
      included in the review (n = 361), all comparing magnesium to placebo. Three of
      these trials included only pregnant women. The difference in the median number of
      leg cramps per week between the placebo and the intervention groups was 0.345
      (quantile 2.5%: -0.133, quantile 97.5%: 0.875). This difference was 0.807
      (quantile 2.5%: 0.015, quantile 97.5%: 1.207) in the three studies involving only
      pregnant women and 0.362 (quantile 2.5%: -0.386, quantile 97.5%: 1.148) in the
      others. Overall gastrointestinal side effects were slightly more common with
      magnesium therapy than with placebo. The strength of this evidence was weak,
      mainly due to small study sizes and short follow-up. CONCLUSIONS: Magnesium
      therapy does not appear to be effective in the treatment of NLC in the general
      population, but may have a small effect in pregnant women. Further research using
      better designed RCTs is necessary.

PMID- 24280948
TI  - Low-dose laser acupuncture for non-specific chronic low back pain: a double-blind
      randomised controlled trial.
AB  - OBJECTIVE: To determine if infrared laser acupuncture (LA) may have a specific
      effect in reducing pain and disability in treatment of chronic low back pain
      (LBP). METHODS: This was a double-blind sham laser controlled trial performed in
      general practices in Perth, Western Australia. The participants were 144 adults
      with chronic non-specific LBP. They were randomised to receive eight once-weekly
      treatments. Laser machines (20 mW, 840 nm diode, power density 0.1 W/cm(2))
      stimulated points in three treatment groups: sham (0 joules/point), low dose (0.2
      J/point) and high dose (0.8 joules/point). Participants were followed-up at 1 and
      6 weeks, and 6 and 12 months post treatment. Primary outcomes were pain
      (Numerical Pain Rating Scale (NPRS)) and disability (Oswestry Disability
      Inventory (ODI)) at 6 weeks post treatment. Secondary outcomes included numerical
      rating scale for limitation of activity, global assessment of improvement,
      analgesic usage and adverse effects after treatment. RESULTS: The analysis showed
      no difference between sham and the laser groups at 6 weeks for pain or
      disability. There was a significant reduction in mean pain and disability in all
      groups at 6 weeks (p<0.005); NPRS: sham (-1.5 (95% CI -2.1 to -0.8)), low dose (
      1.3 (-2.0 to -0.8)), high dose (-1.1 (-1.7 to -0.5)). ODI: sham (-4.0 (-7.1 to 
      1.0)), low dose (-4.1, (-6.7 to -1.5)), high dose (-2.6 (-5.7 to 0.5)). All
      secondary outcomes also showed clinical improvement over time but with no
      differences between groups. CONCLUSIONS: LA using energy density range (0-4
      J/cm(2)) for the treatment of chronic non-specific LBP resulted in clinical
      improvement unrelated to laser stimulation. TRIAL REGISTRATION:
      http://www.anzctr.org.au ACTRN12610000043033.

PMID- 24280949
TI  - Acupuncture treatment of chronic low back pain reverses an abnormal brain default
      mode network in correlation with clinical pain relief.
AB  - BACKGROUND: Acupuncture is gaining in popularity as a treatment for chronic low
      back pain (cLBP); however, its therapeutic mechanisms remain controversial,
      partly because of the absence of an objective way of measuring subjective pain.
      Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode
      network (DMN) connectivity in patients with chronic pain, and also shown that
      acupuncture increases DMN connectivity in pain-modulator and affective-emotional
      brain regions of healthy subjects. OBJECTIVE: This study sought to explore how
      cLBP influences the DMN and whether, and how, the altered DMN connectivity is
      reversed after acupuncture for clinical pain. METHODS: RsfMRI data from 20
      patients with cLBP, before and after 4 weeks of treatment, and 10 age- and gender
      matched healthy controls (without treatment) were analysed using independent
      components analyses to determine connectivity within the DMN, and combined with
      correlation analyses to compute covariance between changes in DMN connectivity
      and changes in clinical pain. Visual analogue scale data were assessed to rate
      clinical pain levels. RESULTS: Less connectivity within the DMN was found in
      patients with cLBP than in healthy controls, mainly in the dorsolateral
      prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and
      precuneus. After acupuncture, patients' connectivities were restored almost to
      the levels seen in healthy controls. Furthermore, reductions in clinical pain
      were correlated with increases in DMN connectivity. CONCLUSIONS: This result
      suggests that modulation of the DMN by acupuncture is related to its therapeutic
      effects on cLBP. Imaging of the DMN provides an objective method for assessment
      of the effects of acupuncture-induced analgesia.

PMID- 24280950
TI  - Randomised clinical trials on acupuncture in the Korean literature: bibliometric
      analysis and methodological quality.
AB  - OBJECTIVE: Acupuncture systematic reviewers have increasingly searched Chinese
      databases and journals to identify eligible randomised clinical trials (RCTs).
      However, reviewers have infrequently searched for eligible RCTs in Korean
      databases and journals. This study aimed to identify difficult to locate
      acupuncture RCTs in Korean databases and journals and to assess the
      characteristics and quality of the identified RCTs. METHODS: Eleven electronic
      databases and seven journals were searched up to December 2012. All RCTs using
      needle acupuncture were considered for inclusion. Key study characteristics were
      extracted and risk of bias was assessed using the Cochrane Collaboration tool.
      RESULTS: One hundred and forty-three publications met our inclusion criteria.
      Acupuncture RCTs in the Korean literature emerged in the mid-1990s and increased
      in the mid-2000s. Diverse methods of acupuncture were used, including some
      methods unique to Korea (eg, Saam acupuncture). The largest proportion of trials
      evaluated acupuncture for musculoskeletal conditions (27.3%). The mean sample
      size was 44.3+/-25.3 per trial. Random sequence generation methods were reported
      in 44.8% of the RCTs, whereas only 11.9% reported methods of allocation
      concealment. A low proportion of trials reported participant blinding (32.9%) and
      outcome assessment blinding (18.9%). CONCLUSIONS: Korean acupuncture trials, many
      of which evaluate acupuncture styles unique to Korea, are typically omitted from
      systematic reviews of acupuncture, resulting in the potential for language bias.
      The development of this database of difficult to locate Korean trials, which
      includes English language translations of abstracts, will enable these trials of
      varying quality to be assessed for inclusion in future acupuncture systematic
      reviews.

PMID- 24280953
TI  - Does Upper Limb Coordination Predict Walking Speed in Older Adults? A Cross
      Sectional Study.
AB  - BACKGROUND AND PURPOSE:: Walking speed is a measure of physical function in older
      adults. Older adults are sometimes nonambulatory, however, and proxy measures for
      walking speed may be indicated. Since limb coordination tests can be conducted in
      non-weight-bearing positions, they may provide that capability. The purpose of
      this study was to examine the relationship between timed limb coordination and
      preferred and maximum walking speed, controlling for other known determinants of
      walking speed. METHODS:: A total of 84 healthy adults (60 women and 24 men) older
      than 60 years participated. Preferred and maximum walking speed were measured
      during 10-Meter Walk Tests. Upper limb coordination performance was measured
      during a timed 5-repetition finger-to-nose test. Other variables measured
      included isometric knee extension strength, cognition (Montreal Cognitive
      Assessment), limits of stability (Functional Reach Test), the number of
      comorbidities (Functional Comorbidity Index), age, height, and sex. Multiple
      regression and partial correlation analyses (alpha = .05) were used to identify
      which variables predicted preferred and maximum walking speed, controlling for
      all other variables. RESULTS:: Participants' mean preferred walking speed was 129
      (24) cm.s, and mean maximum walking speed was 176 (37) cm.s. Finger-to-nose
      coordination performance, 4.8 (1.3) seconds, correlated negatively with preferred
      (r = -0.403) and maximum (r = -0.429) walking speed. Those bivariate correlation
      coefficients, however, were attenuated by other variables in the regression
      models (partial r = -0.031, P = .786, and partial r = -0.075, P = .513, for
      preferred and maximum walking speed, respectively). Variance in age,
      comorbidities, functional reach, knee extension strength, and height accounted
      for 55.4% of the variance in preferred walking speed. Variance in knee extension
      strength, cognition, functional reach, age, and comorbidities accounted for 63.5%
      of the variance in maximum walking speed. After removing knee extension strength
      and functional reach from the models-those variables that may be difficult or
      contraindicated to measure in some patient populations-finger-to-nose
      coordination was not a statistically significant predictor of preferred walking
      speed. Variance in age, comorbidities, cognition, height, and finger-to-nose
      coordination accounted for 55.9% of the variance in maximum walking speed. The
      change in R attributed to finger-to-nose coordination performance, however, was
      only 2.9%. DISCUSSION:: While knee extension strength, functional reach,
      comorbidities, and age were most predictive of walking speed, after removing knee
      extension strength and functional reach from the regression models, finger-to
      nose coordination remained a potentially modifiable marker of neuromuscular
      control that only weakly predicted maximum walking speed in older adults.
      CONCLUSIONS:: The timed finger-to-nose test would not appear to be a valid proxy
      for walking speed when weight-bearing clinical examination procedures are
      contraindicated.

PMID- 24280954
TI  - Protein-mediated dethreading of a biotin-functionalised pseudorotaxane.
AB  - In this article, we describe the synthesis of new biotin-functionalised
      naphthalene derivatives 3 and 4 and their complexation behaviour with avidin and
      neutravidin using a range of analytical techniques. We have shown using 2-(4'
      hydroxyazobenzene)benzoic acid displacement and ITC experiments, that compounds 3
      and 4 have the propensity to form reasonably high-affinity bioconjugates with
      avidin and neutravidin. We have also demonstrated using (1)H NMR, UV-vis and
      fluorescence spectroscopy that the naphthalene moiety of 3 and 4 facilitates the
      formation of pseudorotaxane-like structures with 1 in water. We have then
      investigated the ability of avidin and neutravidin to modulate the complexation
      between 1 and 3 or 4. UV-vis and fluorescence spectroscopy has shown that in both
      cases the addition of the protein disrupts complexation between the naphthalene
      moieties of 3 and 4 with 1. 

PMID- 24280955
TI  - Herniation pits as a radiographic indicator of pincer-type femoroacetabular
      impingement in symptomatic patients.
AB  - PURPOSE: The role of herniation pits as a radiographic indicator is still
      debated. This case-control study was to determine (1) the prevalence and sizes of
      herniation pits and (2) the relationship between herniation pits and femoral and
      acetabular bony morphology consistent with femoroacetabular impingement. METHODS:
      This comparative study was performed on 151 patients (151 hips; median patient
      age 46 years; range 16-73 years) with mechanical symptoms, who underwent multi
      detector computed tomography (MDCT) arthrography (the symptomatic group), and an
      age-, gender-, site (left or right)-, and time (at diagnosis)-matched group of
      control patients that underwent multi-detector computed tomography due to an
      ureter stone (the asymptomatic group). Two orthopaedic surgeons reviewed images
      to evaluate the prevalence, sizes of herniation pits, and relationship with
      morphological abnormality. RESULTS: The prevalences of herniation pits in
      symptomatic and asymptomatic groups were 23.8 % (36/151) and 3.3 % (5/151),
      respectively (OR 9.14, 95 % CI 3.47-24.30; p < 0.001). Herniation pits were found
      to be significantly associated with pincer-type abnormality (p = 0.034),
      especially central acetabular retroversion (p < 0.001). CONCLUSIONS: This study
      shows that the prevalence of herniation pits is higher in symptomatic patients
      with femoroacetabular impingement, and herniation pits are associated with
      central acetabular retroversion. Furthermore, herniation pits were also found to
      be a useful predictor of pincer-type femoroacetabular impingement.

PMID- 24280956
TI  - Healing of donor site in bone-tendon-bone ACL reconstruction accelerated with
      plasma rich in growth factors: a randomized clinical trial.
AB  - PURPOSE: To determine whether the use of plasma rich in growth factors
      accelerates healing of the donor site in bone-tendon-bone anterior cruciate
      ligament (ACL) reconstruction (patellar graft). The use of the patellar graft
      presents post-operative problems such as anterior knee pain, which limits its use
      and leads to preference being taken for alternative grafts. METHODS: A double
      blind, randomized, clinical trial was performed comparing two groups of patients
      who underwent ACL reconstruction using patellar tendon graft and comparing the
      use of plasma rich in growth factors at the donor site after graft harvest in
      terms of local regeneration by ultrasound assessment. RESULTS: The plasma rich in
      growth factors group shows earlier donor site regeneration in comparison with the
      control group (2 months earlier), with significant differences in the first 4
      months of the follow-up. CONCLUSION: The application of plasma rich in growth
      factors shows accelerated tissue regeneration processes with respect to the
      control group. This fact, together with the previously published with similar
      conclusions, can create a knowledge basis in order to set out new recovery
      guidelines following ACL reconstruction. LEVEL OF EVIDENCE: Therapeutic study,
      Level I.

PMID- 24280957
TI  - Effects of acute transmural pressure elevation on endothelium-dependent
      vasodilation in isolated rat mesenteric veins.
AB  - BACKGROUND/AIMS: The vascular regulatory function of the endothelium can be
      impaired by increases in transmural pressure (TMP). We tested the hypothesis that
      increasing TMP impairs the endothelial dilator function of rat mesenteric small
      veins (MSVs). METHODS: In PGF2alpha-preconstricted MSVs, bradykinin (BK), sodium
      nitroprusside (SNP) and S-Nitroso-N-acetylpenicillamine (SNAP) concentration
      response curves were generated at intermediate (6 mm Hg) and high (12 mm Hg)
      pressures. BK-induced vasodilation was examined in the absence and presence of
      nitric oxide synthase inhibitor [N(omega)-nitro-L-arginine (L-NNA), 100 uM],
      cyclooxygenase inhibitor (indomethacin, 1 uM), and large (BKCa, paxilline, 500
      nM) and small (SKCa, apamin, 300 nM) conductance Ca(2+)-activated K(+) channel
      blockers. RESULTS: BK, SNP and SNAP responses were not altered by TMP increases.
      BK-induced vasodilation was significantly reduced by L-NNA, indomethacin, apamin
      and paxilline at 6 mm Hg and L-NNA at 12 mm Hg, and was further reduced by
      coapplication of apamin and/or paxilline with L-NNA compared with responses
      obtained with either blocker. Endothelium removal completely abolished BK-induced
      vasodilation. CONCLUSION: Venous endothelial dilator function is not affected by
      TMP elevation. BK-induced vasodilation is completely dependent on the presence of
      functional endothelial cells and mediated in part by nitric oxide, BKCa and SKCa
      channels, while the participation of prostacyclin may be important at
      intermediate pressures.

PMID- 24280958
TI  - Mechanochemical solid state anion-exchange of lead(II) coordination polymers via
      an intermediate coordination polymer; new precursors for the preparation of
      PbBr2/Pb3O2Br2, PbBr(OH) and PbO nanoparticles.
AB  - The reversible crystal-to-crystal transformations of a 1D lead(II) coordination
      polymer with the ligand 2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene (4-bpdh), from
      [Pb(4-bpdh)Br2]n () to intermediate [Pb(4-bpdh)(Br)(NO3)]n () and [Pb(4
      bpdh)(NO3)2(H2O)]n () by a solid state anion-replacement processes under
      mechanochemical reactions, have been studied. The reversible solid state
      structural transformation of compound to compound and then by anion replacement
      have been verified by PXRD and IR measurements. PbBr2, PbBr(OH), Pb3O2Br2 and PbO
      nanoparticles were obtained by the thermal decomposition of compounds , and in
      oleic acid at 180  degrees C in an air atmosphere, respectively. These
      nanoparticles were characterized by powder X-ray diffraction (PXRD) and scanning
      electron microscopy (SEM).

PMID- 24280959
TI  - Golimumab in patients affected by moderate to severe psoriatic arthritis: an open
      label study in thirty-two patients previously treated with other biologics.
AB  - BACKGROUND: Clinical trials have demonstrated the efficacy of golimumab (GLB) in
      improving the signs and symptoms of psoriatic arthritis (PsA). OBJECTIVE: The aim
      of this study was to evaluate the efficacy of GLB in monotherapy in patients
      affected by PsA with cutaneous involvement unresponsive to other anti-tumor
      necrosis factor-alpha (TNF-alpha) agents. METHODS: This study included 32
      patients treated with GLB as monotherapy, at a dosage of 50 mg, subcutaneously,
      every 4 weeks. Patients were divided into 3 groups (A, B, and C) according to
      their number of previous anti-TNF-alpha treatments (1, 2, or 3). Clinical and
      laboratory evaluations were performed at weeks 0, 12, and 24. RESULTS: All
      patients showed significant improvement of their clinical, inflammatory, and
      quality of life indexes. CONCLUSION: Data suggest that GLB can be successful and
      safe in patients affected by PsA with skin involvement previously treated with
      other anti-TNF-alpha agents.

PMID- 24280960
TI  - Journal of Molecular Endocrinology 25th anniversary special issue.

PMID- 24280962
TI  - Cone beam and micro-computed tomography validation of manual array insertion for
      minimally invasive cochlear implantation.
AB  - Delivering cochlear implants through a minimally invasive tunnel (1.8 mm in
      diameter) from the mastoid surface to the inner ear is referred to as direct
      cochlear access (DCA). Based on cone beam as well as micro-computed tomography
      imaging, this in vitro study evaluates the feasibility and efficacy of manual
      cochlear electrode array insertions via DCA. Free-fitting electrode arrays were
      inserted in 8 temporal bone specimens with previously drilled DCA tunnels. The
      insertion depth angle, procedural time, tunnel alignment as well as the inserted
      scala and intracochlear trauma were assessed. Seven of the 8 insertions were full
      insertions, with insertion depth angles higher than 520 degrees . Three cases of
      atraumatic scala tympani insertion, 3 cases of probable basilar membrane rupture
      and 1 case of dislocation into the scala vestibuli were observed (1 specimen was
      damaged during extraction). Manual electrode array insertion following a DCA
      procedure seems to be feasible and safe and is a further step toward clinical
      application of image-guided otological microsurgery.

PMID- 24280963
TI  - Abortion surveillance - United States, 2010.
AB  - PROBLEM/CONDITION: Since 1969, CDC has conducted abortion surveillance to
      document the number and characteristics of women obtaining legal induced
      abortions in the United States. REPORTING PERIOD COVERED: 2010. DESCRIPTION OF
      SYSTEM: Each year, CDC requests abortion data from the central health agencies of
      52 reporting areas (the 50 states, the District of Columbia, and New York City).
      The reporting areas provide this information voluntarily. For 2010, data were
      received from 49 reporting areas. For the purpose of trend analysis, abortion
      data were evaluated from the 46 areas that reported data every year during 2001
      2010. Census and natality data, respectively, were used to calculate abortion
      rates (number of abortions per 1,000 women) and ratios (number of abortions per
      1,000 live births). RESULTS: A total of 765,651 abortions were reported to CDC
      for 2010. Of these abortions, 753,065 (98.4%) were from the 46 reporting areas
      that provided data every year during 2001-2010. Among these same 46 reporting
      areas, the abortion rate for 2010 was 14.6 abortions per 1,000 women aged 15-44
      years, and the abortion ratio was 228 abortions per 1,000 live births. Compared
      with 2009, the total number and rate of reported abortions for 2010 decreased 3%
      and reached the lowest levels for the entire period of analysis (2001-2010); the
      abortion ratio was stable, changing only 0.4%. From 2001 to 2010, the total
      number, rate, and ratio of reported abortions decreased 9%, 10%, and 8%,
      respectively. Given the 3% decrease from 2009 to 2010 in the total number and
      rate of reported abortions, in combination with the 5% decrease that had occurred
      in the previous year from 2008 to 2009, the overall decrease for both measures
      was greater during 2006-2010 than during 2001-2005, despite the annual variations
      that resulted in no net decrease during 2006-2008. In 2010 and throughout the
      period of analysis, women in their 20s accounted for the majority of abortions
      and had the highest abortion rates, whereas women in their 30s and older
      accounted for a much smaller percentage of abortions and had lower abortion
      rates. In 2010, women aged 20-24 and 25-29 years accounted for 32.9% and 24.5% of
      all abortions, respectively, and had abortion rates of 26.7 and 20.2 abortions
      per 1,000 women aged 20-24 and 25-29 years, respectively. In contrast, women aged
      30-34, 35-39, and >=40 years accounted for 15.3%, 8.9%, and 3.4% of all
      abortions, respectively, and had abortion rates of 13.2, 7.6, and 2.8 abortions
      per 1,000 women aged 30-34 years, 35-39 years, >=40 years, respectively.
      Throughout the period of analysis, abortion rates decreased among women aged 20
      24 and 25-29 years, whereas they increased among women aged >=40 years. In 2010,
      adolescents aged 15-19 years accounted for 14.6% of all abortions and had an
      abortion rate of 11.7 abortions per 1,000 adolescents aged 15-19 years.
      Throughout the period of analysis, the percentage of all abortions accounted for
      by adolescents and the adolescent abortion rate decreased. In contrast to the
      percentage distribution of abortions and abortion rates by age, abortion ratios
      in 2010 and throughout the entire period of analysis were highest among
      adolescents and lowest among women aged 30-39 years. Abortion ratios decreased
      from 2001 to 2010 for women in all age groups except for those aged <15 years,
      for whom they increased. In 2010, most (65.9%) abortions were performed at <=8
      weeks' gestation, and 91.9% were performed at <=13 weeks' gestation. Few
      abortions (6.9%) were performed at 14-20 weeks' gestation, and even fewer (1.2%)
      were performed at >=21 weeks' gestation. From 2001 to 2010, the percentage of all
      abortions performed at <=8 weeks' gestation increased 10%, whereas the percentage
      performed at >13 weeks' decreased 10%. Moreover, among abortions performed at
      <=13 weeks' gestation, the distribution shifted toward earlier gestational ages,
      with the percentage of these abortions performed at <=6 weeks' gestation
      increasing 36%. In 2010, a total of 72.4% of abortions were performed by
      curettage at <=13 weeks' gestation, 17.7% were performed by early medical
      abortion (a nonsurgical abortion at <=8 weeks' gestation), and 8.3% were
      performed by curettage at >13 weeks' gestation. Among abortions that were
      performed at <=8 weeks' gestation, and thus were eligible for early medical
      abortion on the basis of gestational age, 26.5% were completed by this method.
      From 2009 to 2010, the use of early medical abortion increased 13%. Deaths of
      women associated with complications from abortions for 2010 are being
      investigated under CDC's Pregnancy Mortality Surveillance System. In 2009, the
      most recent year for which data were available, eight women were identified to
      have died as a result of complications from known legal induced abortions. No
      reported deaths were associated with illegal induced abortions. INTERPRETATION:
      Among the 46 areas that reported data every year during 2001-2010, the gradual
      decrease that had occurred during previous decades in the total number and rate
      of reported abortions continued through 2005, whereas year-to-year variation from
      2006 to 2008 resulted in no net change during this later period. However, the
      large decreases that occurred both from 2008 to 2009 and from 2009 to 2010
      resulted in a greater overall decrease during 2006-2010 as compared with 2001
      2005 and the lowest number and rate of reported abortions for the entire period
      of analysis. PUBLIC HEALTH ACTIONS: Unintended pregnancy is the major contributor
      to abortion. Because unintended pregnancies are rare among women who use the most
      effective methods of reversible contraception, increasing access to and use of
      these methods can help further reduce the number of abortions performed in the
      United States. The data in this report can help program planners and policy
      makers identify groups of women at greatest risk for unintended pregnancy and
      help guide and evaluate prevention efforts.

PMID- 24280961
TI  - Road to exercise mimetics: targeting nuclear receptors in skeletal muscle.
AB  - Skeletal muscle is the largest organ in the human body and is the major site for
      energy expenditure. It exhibits remarkable plasticity in response to
      physiological stimuli such as exercise. Physical exercise remodels skeletal
      muscle and enhances its capability to burn calories, which has been shown to be
      beneficial for many clinical conditions including the metabolic syndrome and
      cancer. Nuclear receptors (NRs) comprise a class of transcription factors found
      only in metazoans that regulate major biological processes such as reproduction,
      development, and metabolism. Recent studies have demonstrated crucial roles for
      NRs and their co-regulators in the regulation of skeletal muscle energy
      metabolism and exercise-induced muscle remodeling. While nothing can fully
      replace exercise, development of exercise mimetics that enhance or even
      substitute for the beneficial effects of physical exercise would be of great
      benefit. The unique property of NRs that allows modulation by endogenous or
      synthetic ligands makes them bona fide therapeutic targets. In this review, we
      present an overview of the current understanding of the role of NRs and their co
      regulators in skeletal muscle oxidative metabolism and summarize recent progress
      in the development of exercise mimetics that target NRs and their co-regulators. 

PMID- 24280964
TI  - Stent thrombosis with second-generation drug-eluting stents compared with bare
      metal stents: network meta-analysis of primary percutaneous coronary intervention
      trials in ST-segment-elevation myocardial infarction [corrected].
AB  - BACKGROUND: The relative safety of drug-eluting stents (DESs) and bare-metal
      stents (BMSs) with respect to stent thrombosis (ST) continues to be debated.
      There are limited data comparing safety and efficacy of second-generation DES to
      BMS. We compared the clinical outcomes between second-generation DES and BMS for
      primary percutaneous coronary intervention using network meta-analysis. METHODS
      AND RESULTS: Randomized controlled trials comparing stent types (first-generation
      DES, second-generation DES or BMS) were considered for inclusion. A search
      strategy used Medline, Embase, Cochrane databases, and proceedings of the
      international meetings. Information about study design, inclusion criteria, and
      sample characteristics were extracted. Network meta-analysis was used to pool
      direct (comparison of second-generation DES to BMS) and indirect evidence (first
      generation DES with BMS and second-generation DES) from the randomized trials.
      Twenty-one trials comparing all stents types, including 12 866 patients randomly
      assigned to treatment groups, were analyzed. A significantly lower incidence of
      ST was noted with the use of second-generation DES as early as 30 days (odds
      ratio [OR], 0.36; 95% confidence interval [CI], 0.15-0.82) and between 31 days
      and 1 year (OR, 0.49; 95% CI, 0.30-0.79) when compared with BMS. Second
      generation DES was associated with significantly lower incidence of definite ST
      at 1 year (OR, 0.3; 95% CI, 0.11-0.83) and myocardial infarction (OR, 0.3; 95%
      CI, 0.17-0.54) and target vessel revascularization at 1 year (OR, 0.54; 95% CI,
      0.80-0.98) when compared with BMS. There was no difference in mortality at 30
      days (OR, 0.84; 95% CI, 0.45-1.59) or 1 year (OR, 0.80; 95% CI, 0.56-1.14) with
      the use of second-generation DES versus BMS. The small number of events may
      influence the precision of the analysis. CONCLUSIONS: Network meta-analysis of
      randomized trials of primary percutaneous coronary intervention demonstrated
      lower incidence of ST, myocardial infarction, and target vessel revascularization
      with second-generation DES when compared with BMS. The use of second-generation
      DES for percutaneous coronary intervention in ST-segment-elevation myocardial
      infarction was not associated with adverse events when compared with BMS.

PMID- 24280965
TI  - Prevalence, factors associated with, and prognostic effects of preoperative
      anemia on short- and long-term mortality in patients undergoing transcatheter
      aortic valve implantation.
AB  - BACKGROUND: There is scant information on the prevalence and factors associated
      with preoperative anemia in patients undergoing transcatheter aortic valve
      implantation (TAVI) and whether it is associated with mortality. We sought to
      determine the prevalence and factors associated with preoperative anemia in
      addition to the prognostic effects of the various levels of preoperative
      hemoglobin level on mortality in patients undergoing TAVI. METHODS AND RESULTS:
      Ten-center observational study encompassing 1696 patients with aortic stenosis
      who underwent TAVI was conducted. Anemia was defined by the World Health
      Organization criteria (hemoglobin <12.0 g/dL in women and <13.0 g/dL in men). The
      prevalence of preoperative anemia was 57%. Patient-related factors associated
      with preoperative anemia were (descending order of odds ratio [95% confidence
      interval]) as follows: anemia-related medication (4.90 [3.08-7.80]), history of
      heart failure (1.77 [1.43-2.20]), male sex (1.69 [1.32-2.16]), mitral
      regurgitation grade >=III (1.61 [1.15-2.25]), history of malignancy (1.44 [1.03
      2.09]), and peripheral vascular disease (1.33 [1.04-1.70]). The creatinine
      clearance was inversely associated with preoperative anemia (odds ratio, 0.92
      [0.87-0.97]). In multivariable analyses, preoperative anemia was not associated
      with 30-day mortality (1.72 [0.96-3.12]; P=0.073) but showed the strongest
      association with 1-year mortality with a hazard ratio (95% confidence interval)
      of 2.78 (1.60-4.82) in patients with hemoglobin <10 g/dL. Patients with anemia
      received >=1 blood transfusion 2* more often, but the indication of transfusion
      was unrelated to overt bleeding in 60%. Blood transfusion was associated with
      mortality at 30 days (odds ratio, 1.25 [95% confidence interval, 1.08-3.67]) and
      during follow-up (hazard ratio, 1.09 [95% confidence interval, 1.03-1.14]).
      CONCLUSIONS: Preoperative anemia is prevalent in >50% of patients undergoing
      TAVI. Various baseline factors were related to anemia, which in turn was
      associated with 1-year mortality. Patients with anemia received more transfusions
      but mostly for indications unrelated to overt bleeding, whereas transfusion was
      independently associated with both early and 1-year mortality. These findings
      indicate that optimization of baseline factors related to preoperative anemia, in
      addition to more strict criteria of the use of blood products, may improve
      outcome after TAVI.

PMID- 24280966
TI  - Impact of worsening renal dysfunction on the comparative efficacy of bivalirudin
      and platelet glycoprotein IIb/IIIa inhibitors: insights from Blue Cross Blue
      Shield of Michigan Cardiovascular Consortium.
AB  - BACKGROUND: Use of bivalirudin has been associated with a reduction in the
      incidence of bleeding in patients undergoing percutaneous coronary intervention.
      Patients with chronic kidney disease, a known predictor of post-percutaneous
      coronary intervention bleeding, are under-represented in clinical trials. METHODS
      AND RESULTS: We evaluated the outcome of 64,052 patients who underwent
      percutaneous coronary intervention from 2007 to 2009 at 33 hospitals in Michigan
      and were treated with bivalirudin (28,378) or with heparin and glycoprotein
      IIb/IIIa inhibitors (35,674). Propensity-matched analysis was adjusted for the
      nonrandomized use of the 2 strategies. Patients treated with bivalirudin were
      older, had a lower glomerular filtration rate, and had more comorbidities. Use of
      bivalirudin was associated with fewer transfusions (2.8% versus 4.2%; P<0.0001),
      gastrointestinal bleeds (0.5% versus 1.3%; P<0.0001), and vascular complications
      (1.0% versus 2.5%; P<0.0001), with no difference in survival. Bleeding
      complications were more common with worsening renal function, but use of
      bivalirudin was associated with less bleeding across the continuum of renal
      dysfunction. CONCLUSIONS: The risk of bleeding after percutaneous coronary
      intervention increases with worsening chronic kidney disease. Bivalirudin was
      associated with a dramatically reduced risk of bleeding across all categories of
      renal dysfunction. Our study findings suggest that bivalirudin monotherapy is an
      acceptable, if not the more appropriate alternative, to heparin and glycoprotein
      IIb/IIIa inhibitors in patients with chronic kidney disease.

PMID- 24280967
TI  - Polypoidal choroidal vasculopathy: clinical features and genetic predisposition.
AB  - Polypoidal choroidal vasculopathy (PCV) is currently recognized as a phenotype of
      age-related macular degeneration (AMD). PCV is believed to be a type of choroidal
      neovascularization, although some cases of PCV show a distinct vascular
      abnormality of the choroidal vessels. PCV often shows several unique clinical
      manifestations which are apparently different from typical neovascular AMD
      (tAMD). In addition, the natural course and response to treatment are often
      different between tAMD and PCV. Moreover, recent genetic studies suggested a
      possible difference in the genetic susceptibility to disease between tAMD and
      PCV, as well as the existence of heterogeneity among PCV cases. In viewing the
      accumulation of knowledge about PCV, we have summarized the recent literature
      regarding PCV in this review article to improve the understanding of this
      clinical entity including possible susceptibility genes. We will also discuss the
      optimal treatment strategies for PCV in accordance with the results of recent
      clinical and genetic studies.

PMID- 24280968
TI  - BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in
      Histologically Advanced Adenomas.
AB  - We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in
      normal tissues and hypomethylated in 98% of human cancers. More recently, we
      provided evidence that hypomethylation of BAGE loci represents an informative
      marker for colon cancer detection. In this study, we show that hypomethylation of
      BAGE loci was an early event that occurred in 43% of colorectal adenomas.
      Interestingly, hypomethylation of BAGE loci was frequent (50%) in tubulo-villous
      and villous adenomas, these adenomas having a high probability of being
      transformed into colorectal cancers. 

PMID- 24280969
TI  - Comparison of Locoregional Recurrence with Mastectomy vs. Breast Conserving
      Surgery in Pregnancy Associated Breast Cancer (PABC).
AB  - We have compared outcomes, including the locoregional recurrence, between
      mastectomy and breast conserving therapy in PABC. Patients were divided into
      those who were treated with mastectomies (group 1) and those with breast
      conserving surgery (group 2). The groups were comparable except for lower mean
      age in group 2 and more patients with stage III disease and higher number of
      nodes positive in the group 1. Five-year actuarial LRR, distant metastases free
      survival and overall survival in group 1 vs. 2 were 10% vs. 37%, 73% vs. 81% and
      57% vs. 59% respectively. The patients with PABC treated with breast conserving
      therapy, despite having lower stage disease, have a higher risk of local regional
      recurrence in comparison with those treated with mastectomy. 

PMID- 24280970
TI  - Human umbilical cord-derived mesenchymal stem cells downregulate inflammatory
      responses by shifting the Treg/Th17 profile in experimental colitis.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the effect and mechanisms
      of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on immune
      responses in murine colitis. METHODS: Mice with dextran sulfate sodium (DSS)
      induced colitis were injected intraperitoneally with hUC-MSCs or human bone
      marrow-derived MSCs. The cytokine levels from lamina propria mononuclear cells
      (LPMCs) and colon tissue were measured using ELISA. Treg and Th17 cells were
      analyzed using flow cytometry. The proliferation of LPMCs was assessed using Cell
      Counting Kit-8. RESULTS: hUC-MSCs ameliorate DSS-induced colitis via the
      downregulation of colon inflammatory responses. Furthermore, hUC-MSCs adjusted
      modulation of Treg/Th17 cells in the spleen and mesenteric lymph nodes. hUC-MSCs
      also inhibited LPMCs in vitro. CONCLUSION: hUC-MSCs may be an alternative source
      of stem cells and are worthy of study in long-term clinical trials.

PMID- 24280971
TI  - Live attenuated hepatitis A vaccines developed in China.
AB  - Two live, attenuated hepatitis A vaccines, H 2 and LA-1 virus strains, were
      developed through serial passages of the viruses in cell cultures at 32  degrees
      C and 35  degrees C respectively. Both vaccines were safe and immunogenic,
      providing protection against clinical hepatitis A in 95% of the vaccinees, with a
      single dose by subcutaneous injection. The vaccine recipients were not protected
      from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a
      similar antibody response as for unvaccinated subjects. A second dose caused
      anamnestic response and can be used for boosting. Oral immunization of human with
      H 2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found
      for person-to-person transmission of the H 2 strain or for marmoset-to-marmoset
      transmission of LA-1 strain, by close contact. H 2 strain was genetically stable
      when passaged in marmosets, humans or cell cultures at 37  degrees C; 3
      consecutive passages of the virus in marmosets did not cause virulence mutation.
      The live vaccines offer the benefits of low cost, single dose injection, long-
      term protection, and increased duration of immunity through subclinical
      infection. Improved sanitation and administration of 150 million doses of the
      live vaccines to children had led to a 90% reduction in the annual national
      incidence rate of hepatitis A in China during the 16-year period, from 1991 to
      2006. Hepatitis A immunization with both live and inactivated HA vaccines was
      implemented in the national routine childhood immunization program in 2008 and
      around 92% of the 16 million annual births received the affordable live,
      attenuated vaccines at 18 months of age. Near elimination of the disease was
      achieved in China for 14 years following introduction of the H 2 live vaccine
      into the Expanded Immunization Program (EPI) in 1992. 

PMID- 24280972
TI  - Potential beneficial uses of coalbed natural gas (CBNG) water.
AB  - The CBNG well water is typically managed by discharging into nearby disposal
      ponds. The CBNG well water could potentially be very useful in the water-limited
      regions (e.g., arid and semi-arid), but beneficial uses may be hindered by water
      quality problems. Objectives of this research were to: (1) examine trend analysis
      of nine years of CBNG well water at discharge (outfall) points and in
      corresponding disposal ponds, (2) evaluate geochemical processes, (3) identify
      potential water quality issues, and (4) find potential beneficial uses. The CBNG
      well water at discharge points and in corresponding disposal ponds was measured
      on-site for pH and electrical conductivity (EC). These water samples were also
      analyzed in the laboratory for calcium (Ca), sodium (Na), magnesium (Mg),
      potassium (K), iron (Fe), aluminum (Al), copper (Cu), arsenic (As), selenium
      (Se), cadmium (Cd), and barium (Ba). Total dissolved solids (TDS) were calculated
      from EC measurements. The sodium adsorption ratio (SAR) was calculated from Na,
      Ca, and Mg concentrations. Trend analyses of outfalls and disposal ponds were
      conducted separately so that the differences in trends could be compared. Trends
      in CBNG well water at discharge points are not always the same as trends in CBNG
      disposal ponds: environmental and geochemical processes play an important role in
      the water quality of these well waters. Overall trend analyses suggest that CBNG
      well water at discharge points in all basins of the Powder River Basin meets
      beneficial use criteria, except for SAR and to some extent EC, for aquatic life,
      livestock and wildlife watering, and irrigation. The CBNG well water in disposal
      ponds across all basins meets criteria for all beneficial uses except for As, pH,
      SAR, and to some extent EC for irrigation, aquatic life, and livestock and
      wildlife watering. 

PMID- 24280973
TI  - Hypertension knowledge, awareness, and self-management behaviors affect
      hypertension control: a community-based study in Xuhui District, Shanghai, China.
AB  - OBJECTIVE: To investigate correlations between hypertensive patients' knowledge
      of hypertension, awareness of hypertension education, self-management behaviors,
      and hypertension control. METHODS: Hypertensive patients from 5 community health
      centers in Xuhui District, Shanghai, China, were enrolled into this study. Data
      were collected via patient interviews and a questionnaire survey. Independent
      influence factors for hypertension control were identified by logistic regression
      analysis. RESULTS: In total, 3,328 hypertensive patients, including 1,935 females
      and 1,390 males with a mean age 70.6 years, were studied. The mean systolic blood
      pressure was 133.1 mm Hg. The mean diastolic blood pressure was 80.5 mm Hg.
      Hypertension was controlled in 1,050 (36.1%) patients. Independent influence
      factors for failed hypertension control were comorbidities, including diabetes
      mellitus, coronary artery disease, and stroke. Patients who knew that 'high blood
      pressure is related to salt intake' and were willing to receive regular health
      education were less likely to fail in hypertension control. Patients who visited
      clinics because of fear of complications and visited medical institutions other
      than community health centers for hypertension were more likely to fail in
      hypertension control. CONCLUSIONS: In Shanghai, failed hypertension control is
      significantly associated with chronic disease history. Limiting salt intake,
      receiving regular health education, and visiting community health centers for
      hypertension care may help control hypertension.

PMID- 24280974
TI  - Catalytic intermolecular beta-C-H alkenylation of alpha-enamino-ketones with
      simple alkynes.
AB  - A unique strategy to synthesize beta-alkenylated alpha-enamino-ketones via
      catalytic C-H/alkyne coupling is described. The slow addition of alkyne
      substrates and the use of NaI as an additive play key roles in controlling the
      alkyne insertion. Replacement of the pyridyl group with carbamates was also
      developed. This method allows for rapid synthesis of highly functionalized vinyl
      substituted enamino-ketones. 

PMID- 24280975
TI  - A grounded explanation of why women present with advanced breast cancer.
AB  - BACKGROUND: Advanced breast cancer presentation remains a large obstacle in
      lowering mortality rates in low- and middle-resource countries. This study aims
      to explore the reasons why women present with breast cancer at an advanced stage.
      METHODS: Purposive sampling of 19 breast cancer patients presenting with advanced
      cancer that were diagnosed within 2 years at the University Malaya Medical
      Centre, Kuala Lumpur, Malaysia. In-depth interviews were conducted, and audio
      recordings were transcribed. Sample size was determined by theoretic sufficiency,
      and the constructivist grounded theory method was used. RESULTS: The reasons for
      delayed presentation can be displayed in two models. The total breast cancer
      delay (TBCD) model was derived from the journey of the patients. Four concepts
      emerged: (1) pluralistic health systems; (2) points of delay; (3) presence of
      patient or system delays, and (4) patient decision-making at each stage. Eight
      points of delay were found. At each point, evidence of a patient decision-making
      model emerged: the breast cancer delay explanatory (BCDE) model, which was the
      process of assessing severity and knowing and choosing options. The four main
      operational constructs were (1) knowledge on disease and disease outcomes, (2)
      knowledge of treatment and treatment outcomes, (3) psychological and physical
      resources and support; and (4) roles in decision-making. CONCLUSIONS: The
      phenomenon is explained by the TBCD and BCDE models. Deconstructing why women
      present with advanced breast cancer and resist treatment provides clarity of the
      issues and opportunities for intervention.

PMID- 24280976
TI  - Long-term outcome of patients with acute cholecystitis receiving antibiotic
      treatment: a retrospective cohort study.

PMID- 24280977
TI  - Endoscopic evaluation of laparoscopic nissen fundoplication: 89 % success rate 10
      years after surgery.
AB  - BACKGROUND: The surgical outcome of fundoplication can be evaluated by means of
      esophagogastroduodenoscopy (EGDS). The literature reveals only one prior long
      term follow-up series with endoscopic evaluation of the fundoplication wraps
      after laparoscopic Nissen fundoplication (LNF). The results achieved at a
      university clinic showed LNF to be more durable than open fundoplication (ONF).
      Previously, in our community-based hospital, the results of ONF were somewhat
      poorer than those achieved at a university clinic. The objective of the present
      study was to describe the long-term results of LNF in our hospital as regards
      surgical and symptomatic outcomes. METHODS: In 1997-1999, 107 LNFs were performed
      in our hospital. A questionnaire with symptom evaluation was mailed to all
      patients. The patients who agreed to participate were interviewed and underwent
      EGDS. RESULTS: Of the 107 patients, 64 (59.8 %) participated in the study (40
      men, mean age 61.9 years, range 28-85 years). The mean follow-up time was 9.8
      years. Seven endoscopic examinations (10.9 %) showed a defective fundic wrap;
      three of the patients had undergone reoperation. Fifty-eight (90.6 %) patients
      had no or minimal heartburn and 61 (95.3 %) had no or minimal regurgitation.
      Twenty-three (35.9 %) patients had moderate or severe dysphagia, and 43 (67.2 %)
      patients had moderate or severe flatulence. Fifty-seven (89.1 %) patients would
      have opted for surgery again. CONCLUSIONS: This study contributes to the previous
      notion that LNF is associated with fewer surgical failures than ONF. Our results
      indicate that LNF can well be performed in a community-based hospital with
      acceptable long-term results.

PMID- 24280978
TI  - Significance of preoperative evaluation of the right gastroepiploic artery graft
      to the coronary artery in patients undergoing abdominal surgery.
AB  - BACKGROUND: A major concern with the use of the right gastroepiploic artery
      (RGEA) as the graft for coronary artery bypass grafting (CABG) is the potential
      for injury, which can result in critical myocardial ischemia during future
      abdominal surgery. METHODS: We examined the availability of preoperative image
      evaluation, preoperative recognition of the RGEA graft, and operative findings
      such as graft identification, graft injury, and cardiac events in 11 patients who
      underwent abdominal surgery after CABG using the RGEA as the graft. RESULTS:
      Prior to the abdominal surgery, contrast-enhanced computed tomography (CT) was
      performed in all 11 patients, while coronary angiography or three-dimensional CT
      angiography was performed in five patients. We detected the RGEA graft
      retrospectively in nine of ten patients in whom the images from contrast-enhanced
      CT were still available. Among the seven patients whose RGEA grafts were in the
      operative field, the RGEA graft was identified in five patients, while the RGEA
      graft was not identified in the remaining two patients because of adhesions.
      There were no intraoperative cardiac events in any of the 11 patients.
      CONCLUSIONS: It is important to determine whether an RGEA graft is present when
      repeat laparotomy is required after CABG. In cases where an RGEA graft is
      present, it is essential to evaluate the patency and location of the graft since
      this will be crucial for planning the reoperation strategy. Preoperative
      recognition and evaluation of the RGEA graft can help avoid graft injury, even if
      the graft cannot be detected intraoperatively.

PMID- 24280979
TI  - Surgeons are overlooking post-discharge complications: a prospective cohort
      study.
AB  - INTRODUCTION: The registration of surgical complications is an important quality
      indicator of hospital medical care. Previous research has suggested that surgeons
      only record certain complications after discharge. The extent and impact of this
      potential under-recording of post-discharge complications is unknown. Therefore,
      we aimed to determine the frequency, type, and grade of post-discharge
      complications as reported by patients and their surgeons. METHODS: A prospective
      cohort study was performed in the Department of Surgery of a University Medical
      Center. From December 2008 until August 2009, all adult surgical patients were
      interviewed by phone or questionnaire 1 month after their discharge to inquire
      about any new complications after discharge. These complications were compared
      with the surgeon-reported post-discharge complications and letters from the
      outpatient clinic as documented in the patients' medical files. RESULTS: A total
      of 976 patients were included. Patients reported more complications (659) than
      did surgeons (465), especially psychological disturbances (4.2 vs. 0 %). A
      medical consult was needed in 527 (80 %) of the patient-reported complications.
      Of all patient-reported complications, 291 (44 %) resulted in a visit to the
      outpatient clinic, 144 (22 %) in a consultation with a general practitioner, and
      92 (14 %) led to referral to a hospital; 743 (76 %) were treated non-operatively.
      CONCLUSION: Surgeons are unaware of many of the complications their patients
      experience after discharge. These post-discharge complications are important to
      patients and are therefore relevant to be aware of and to act upon whenever
      necessary.

PMID- 24280980
TI  - In situ approach for testing the enantiopurity of chiral amines and amino
      alcohols by 1H NMR.
AB  - An in situ approach involving a simple mix and shake method for testing the
      enantiopurity of primary, secondary and tertiary chiral amines and their
      derivatives, chiral amino alcohols, by (1)H-NMR spectroscopy is developed. The
      protocol involves the in situ formation of chiral ammonium borate salt from a
      mixture of C2 symmetric chiral BINOL, trialkoxyborane and chiral amines. The
      proposed concept was demonstrated convincingly on a large number of chiral and
      pro-chiral amines and amino alcohols, and also aids the precise measurement of
      enantiomeric excess. The protocol can be completed in a couple of minutes
      directly in the NMR sample tube, without the need for any physical separation. 

PMID- 24280982
TI  - Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and
      schizophrenia.
AB  - Bipolar disorder and schizophrenia are two often severe disorders with high
      heritabilities. Recent studies have demonstrated a large overlap of genetic risk
      loci between these disorders but diagnostic and molecular distinctions still
      remain. Here, we perform a combined genome-wide association study (GWAS) of 19
      779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls,
      in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases.
      In our case-control analysis, we identify five previously identified regions
      reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a
      novel locus near PIK3C2A. We create a polygenic risk score that is significantly
      different between BP and SCZ and show a significant correlation between a BP
      polygenic risk score and the clinical dimension of mania in SCZ patients. Our
      results indicate that first, combining diseases with similar genetic risk
      profiles improves power to detect shared risk loci and second, that future direct
      comparisons of BP and SCZ are likely to identify loci with significant
      differential effects. Identifying these loci should aid in the fundamental
      understanding of how these diseases differ biologically. These findings also
      indicate that combining clinical symptom dimensions and polygenic signatures
      could provide additional information that may someday be used clinically. 

PMID- 24280985
TI  - Anti-osteoporotic drugs and vascular calcification: the bidirectional calcium
      traffic.
AB  - During the last years, numerous epidemiological studies have demonstrated a
      direct relationship between vascular calcification and low bone mineral density.
      This observation is in line with experimental data demonstrating the osteogenic
      characteristics of calcified arteries. Various common risk factors have been
      suggested to link vascular calcification and bone loss, including aging, estrogen
      deficiency, vitamin D and K deficiency, diabetes mellitus, renal failure,
      smoking, chronic inflammation and oxidative stress. Although the underlying
      pathogenetic mechanisms are not yet clear, current research is focusing on anti
      osteoporotic agents that could potentially affect the deposition of calcium in
      the arterial wall and thus provide an additional therapeutic strategy in elderly
      osteoporotic women prone to calcific cardiovascular disease.

PMID- 24280983
TI  - A model for streamlining psychotherapy in the RDoC era: the example of 'Engage'.
AB  - A critical task for psychotherapy research is to create treatments that can be
      used by community clinicians. Streamlining of psychotherapies is a necessary
      first step for this purpose. We suggest that neurobiological knowledge has
      reached the point of providing biologically meaningful behavioral targets, thus
      guiding the development of effective, simplified psychotherapies. This view is
      supported by the Research Domain Criteria (RDoC) Project, which reflects the
      field's consensus and recognizes the readiness of neurobiology to guide research
      in treatment development. 'Engage' is an example of such a streamlined therapy.
      It targets behavioral domains of late-life depression grounded on RDoC constructs
      using efficacious behavioral strategies selected for their simplicity. 'Reward
      exposure' targeting the behavioral expression of positive valence systems'
      dysfunction is the principal therapeutic vehicle of 'Engage'. Its first three
      sessions consist of direct 'reward exposure', but the therapists search for
      barriers in three behavioral domains, that is, 'negativity bias' (negative
      valence), 'apathy' (arousal) and 'emotional dysregulation' (cognitive control),
      and add strategies targeting these domains when needed. The end result is a
      structured, stepped approach using neurobiological constructs as targets and as a
      guide to personalization. We argue that the 'reduction' process needed in order
      to arrive to simplified effective therapies can be achieved in three steps: (1)
      identify RDoC constructs driving the syndrome's psychopathology; (2) create a
      structured intervention utilizing behavioral and ecosystem modification
      techniques targeting behaviors related to these constructs; (3) examine whether
      the efficacy of the new intervention is mediated by change in behaviors related
      to the targeted RDoC constructs. 

PMID- 24280986
TI  - Resident research: the resident's unheard voice.

PMID- 24280987
TI  - Simulation curriculum can improve medical student assessment and management of
      acute coronary syndrome during a clinical practice exam.
AB  - BACKGROUND: It has been noted that increased focus on learning acute care skills
      is needed in undergraduate medical curricula. This study investigated whether a
      simulation-based curriculum improved a senior medical student's ability to manage
      acute coronary syndrome as measured during a clinical performance examination
      (CPX). The authors hypothesized that simulation training would improve overall
      performance when compared with targeted didactics or historical controls.
      METHODS: All 4th-year medical students (n = 291) over 2 years at the authors'
      institution were included in this study. In the 3rd year of medical school, the
      "control" group received no intervention, the "didactic" group received a
      targeted didactic curriculum, and the "simulation" group participated in small
      group simulation training and the didactic curriculum. For intergroup comparison
      on the CPX, the authors calculated the percentage of correct actions completed by
      the student. Data are presented as mean +/- standard deviation with significance
      defined as P < 0.05. RESULTS: There was a significant improvement in overall
      performance with simulation versus both didactics and control (P < 0.001).
      Performance on the physical examination component was significantly better in
      simulation versus both didactics and control, as was for diagnosis: simulation
      versus both didactics and control (P < 0.02 for all comparisons). CONCLUSIONS:
      Simulation training had a modest impact on overall CPX performance in the
      management of a simulated acute coronary syndrome. Additional studies are needed
      to evaluate how to further improve curricula regarding unstable patients.

PMID- 24280988
TI  - Bilateral lacrimal gland involvement with mantle cell lymphoma.

PMID- 24280989
TI  - Anemia and iron deficiency in children: association with red meat and poultry
      consumption.
AB  - OBJECTIVE: The aim of this study was to study the relative contribution of
      dietary sources of iron in children with high prevalence of anemia and iron
      deficiency (ID). METHODS: A cross-sectional study in 263 healthy, 1.5- to 6-year
      old children in the Jewish sector of Jerusalem, Israel. Venous blood samples and
      a qualitative Food Frequency Questionnaire on iron-rich foods were obtained.
      Anemia was defined as hemoglobin <11 g/dL for children younger than 4 years and
      <11.5 g/dL for children older than 4 years; ID was defined as ferritin <12 MUg/L.
      RESULTS: Anemia was found in 11.2%, ID in 22%, and iron-deficiency anemia in
      3.7%. The prevalence of anemia was higher in toddlers ages 1.5 to 3 years
      compared with children ages 3 to 6 years (17.7% vs 7.3%, P = 0.01). Children with
      extremely low red meat consumption (seldom) had 4-fold higher rates of ID than
      those who consumed >=2 times per week (odds ratio 3.98; 95% confidence interval
      1.21-13.03; P = 0.023), whereas poultry consumption was not associated with ID.
      Soy consumption was inversely associated with ferritin (marginally significant, r
      = -0.134, P = 0.057). CONCLUSIONS: The high prevalence of anemia and ID found in
      this study, mainly in children 1.5 to 3 years old, is related to low red meat
      consumption. The characteristically high poultry consumption in the Israeli
      population was not protective. The shift toward reduced red meat consumption and
      higher poultry consumption in developed countries may result in increasing the
      risk of ID.

PMID- 24280990
TI  - Lactobacillus rhamnosus GG on rotavirus-induced injury of ileal epithelium in
      gnotobiotic pigs.
AB  - OBJECTIVE: The aim of this study was to study the effect of continued
      Lactobacillus rhamnosus GG strain (LGG) feeding on rotavirus gastroenteritis in
      the gnotobiotic (Gn) pig model of virulent human rotavirus (HRV) infection.
      METHODS: Gn pigs were assigned to treatment groups: mock control, LGG only, HRV
      only, or LGG plus HRV. Nine days before HRV inoculation (3 days of age), pigs
      were fed LGG with a daily dose increase of 10-fold from 103 to 1012 colony
      forming units (CFU). The 1012 CFU/dose of LGG feeding continued until post-HRV
      inoculation day (PID) 6. Clinical sign (diarrhea), rotavirus fecal shedding,
      histopathology of the ileum, adherent junction and tight junction protein
      expression in the ileal epithelial cells, mucin production in the large and small
      intestinal contents, and serum cytokine responses from PID 2 to 6 were examined
      and compared among the treatment groups. RESULTS: Clinically, the percentage of
      pigs developing diarrhea, the mean duration of diarrhea, and the mean cumulative
      fecal scores were lower in the LGG fed pigs compared to the nonfed pigs after HRV
      inoculation. LGG partially protected ileal epithelium against HRV-induced
      compensatory increases of the adherent junction protein alpha-catenin and beta
      catenin, tight junction protein occludin, claudin-3 and claudin-4, and leak
      protein claudin-2. LGG promoted mucin production because the mucin levels in the
      large intestinal contents of the LGG+HRV pigs were significantly higher than the
      HRV-only pigs on PID 2. Additionally, LGG maintained the anti-inflammatory
      cytokine transforming growth factor-beta level in serum after HRV infection.
      CONCLUSIONS: LGG is moderately effective for ameliorating rotavirus diarrhea by
      partially preventing injuries to the epithelium.

PMID- 24280992
TI  - Enteric neural disruption in necrotizing enterocolitis occurs in association with
      myenteric glial cell CCL20 expression.
AB  - OBJECTIVE: The aetiology of necrotising enterocolitis (NEC) is unknown, but
      luminal factors and epithelial leakiness appear critical triggers of an
      inflammatory cascade. A separate finding has been suggested in mouse models, in
      which disruption of glial cells in the myenteric plexus induced a severe NEC-like
      lesion. We have thus looked for evidence of neuroglial abnormality in NEC.
      METHODS: We studied full-thickness resected specimens from 20 preterm infants
      with acute NEC and from 13 control infants undergoing resection for other
      indications. Immunohistochemical analysis was performed for immunological (CD3,
      syndecan-1, human leucocyte antigen-DR), neural (glial fibrillary acidic protein
      [GFAP], nerve growth factor receptor, neurofilament protein, neuron-specific
      enolase), and functional markers (Ki67), and for potential inflammatory
      regulators (interleukin-12, transforming growth factor-beta, CCL20, CCR6).
      RESULTS: Expression of the chemokine CCL20 and its receptor CCR6 was
      significantly upregulated in myenteric plexus in NEC, with CCL20 strongly
      expressed by glial cells. In 9 of 20 cases with NEC, myenteric plexus
      architecture and GFAP+ glial cells were normal, with preserved submucosal and
      mucosal innervation; however, 11 cases showed disrupted myenteric plexus
      architecture, reduced GFAP expression, and loss of submucosal and mucosal
      innervation. Persistent abnormalities were identified in the 2 infants who had
      ongoing inflammation at ileostomy closure. CONCLUSIONS: Our findings identified
      heterogeneity among patients with NEC. Approximately half showed evidence of
      marked neural abnormality extending from the deeper layers of the intestine,
      associated with glial activation and myenteric plexus disruption. The factors
      that may activate enteric glia in this manner, potentially including bacterial
      products or viruses, remain to be determined.

PMID- 24280991
TI  - Exome sequencing finds a novel PCSK1 mutation in a child with generalized
      malabsorptive diarrhea and diabetes insipidus.
AB  - OBJECTIVES: Congenital diarrhea disorders are a group of genetically diverse and
      typically autosomal recessive disorders that have yet to be well characterized
      phenotypically or molecularly. Diagnostic assessments are generally limited to
      nutritional challenges and histologic evaluation, and many subjects eventually
      require a prolonged course of intravenous nutrition. Here we describe next
      generation sequencing techniques to investigate a child with perplexing
      congenital malabsorptive diarrhea and other presumably unrelated clinical
      problems; this method provides an alternative approach to molecular diagnosis.
      METHODS: We screened the diploid genome of an affected individual, using exome
      sequencing, for uncommon variants that have observed protein-coding consequences.
      We assessed the functional activity of the mutant protein, as well as its lack of
      expression using immunohistochemistry. RESULTS: Among several rare variants
      detected was a homozygous nonsense mutation in the catalytic domain of the
      proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes
      prohormone convertase 1/3 endoprotease activity as well as expression in the
      intestine. These primary genetic findings prompted a careful endocrine
      reevaluation of the child at 4.5 years of age, and multiple significant problems
      were subsequently identified consistent with the known phenotypic consequences of
      proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on
      the molecular diagnosis, alternate medical and dietary management was implemented
      for diabetes insipidus, polyphagia, and micropenis. CONCLUSIONS: Whole-exome
      sequencing provides a powerful diagnostic tool to clinicians managing rare
      genetic disorders with multiple perplexing clinical manifestations.

PMID- 24280993
TI  - Colonic lymphoid nodular hyperplasia in childhood: causes of familial
      Mediterranean fever need extra attention.
AB  - OBJECTIVES: The clinical importance and etiology of colonic lymphoid nodular
      hyperplasia (LNH) are not clear. It has been considered a response to some
      antigenic stimuli. Although food allergies, infections, inflammatory bowel
      diseases, and immunodeficiencies may be listed in the etiology of colonic LNH,
      the etiology has remained unclear in many cases. This study investigated the
      etiology of colonic LNH and its relation to familial Mediterranean fever (FMF) in
      children. FMF as an etiologic factor for colonic LNH has not been reported before
      in the literature. METHODS: Medical files of patients who underwent colonoscopy
      between 2007 and 2011 were examined retrospectively. Demographic features,
      presenting symptoms, colonoscopy indications, colonoscopic findings, and final
      diagnoses of patients were evaluated. According to etiologies, patients with
      colonic LNH were divided into 2 groups: group A consisted of patients with FMF
      and group B consisted of diseases other than FMF. RESULTS: A total of 311
      patients were included in the study. Forty (12.6%) patients had isolated colonic
      LNH. In 23 (57.5%) patients, isolated LNH was observed in some colonic segments
      and total colonic LNH was noted in 17 (42.5%) patients. FMF was the etiologic
      factor in 6 (15%) patients. Thirty-four patients (85%) had etiologic factors
      other than FMF. We did not find any etiologic factor for LNH in 3.53% (11/311) of
      patients. CONCLUSIONS: FMF may be an etiologic factor for colonic LNH in children
      besides food allergies, infections, inflammatory bowel diseases, and
      immunodeficiencies.

PMID- 24280994
TI  - Pain and embarrassment associated with urodynamic testing in women.
AB  - INTRODUCTION: Multichannel urodynamics is a series of interactive tests used to
      evaluate lower urinary tract dysfunction. We sought to describe symptoms and
      satisfaction in a cohort of women undergoing these procedures. METHODS: Females
      undergoing urodynamics completed questionnaires immediately (Q1) and 1 week (Q2)
      after their testing. Surveys utilized visual analog scales (VAS) from 0 to 10 to
      assess pain, embarrassment, anxiety, and satisfaction. Q2 also inquired about
      urinary symptoms in the days following the procedure. RESULTS: 100 women were
      analyzed. Regarding symptoms on the day of testing, VAS scores indicated low
      bother; with a median of 1.5/10 for pain, 0.4/10 for embarrassment, and 1.8/10
      for anxiety. One week following, recall of pain (p = 0.169), and embarrassment (p
      = 0.722) were similar. Further analyses suggested that overactive bladder
      syndrome (OAB) might be associated with greater pain during and after the
      procedure (p = 0.04, p = 0.038 respectively), while depression was associated
      with greater embarrassment at those times (p = 0.018, p = 0.027 respectively).
      Painful bladder syndrome (PBS) was associated with a higher recall of pain (p =
      0.018), and anxiety with more embarrassment (p = 0.033) on the second survey.
      Finally, younger age correlated with higher pain on both questionnaires (Q1: tau
      = - 0.148, p = 0.029; Q2: tau = - 0.171, p = 0.014). Following urodynamics,
      urgency was most common (43%), generally resolving within 1 day. Reassuringly,
      86% would repeat urodynamics if necessary, and overall satisfaction was rated
      >=9/10 at both time points. CONCLUSION: Urodynamic testing is well-tolerated in
      women. Nevertheless, younger age, anxiety or depression, and a diagnosis of OAB
      and PBS may lead to more negative experiences. Such information may be useful in
      counseling future patients.

PMID- 24280996
TI  - When the body attacks the brain.

PMID- 24280995
TI  - Exercise-associated changes in the corticosterone response to acute restraint
      stress: evidence for increased adrenal sensitivity and reduced corticosterone
      response duration.
AB  - Exercise promotes stress resistance and is associated with reduced anxiety and
      reduced depression in both humans and in animal models. Despite the fact that
      dysfunction within the hypothalamic pituitary adrenal (HPA) axis is strongly
      linked to both anxiety and depressive disorders, the evidence is mixed as to how
      exercise alters the function of the HPA axis. Here we demonstrate that 4 weeks of
      voluntary wheel running was anxiolytic in C57BL/6J mice and resulted in a shorter
      time to peak corticosterone (CORT) and a more rapid decay of CORT following
      restraint stress. Wheel running was also associated with increased adrenal size
      and elevated CORT following systemic administration of adrenocorticotropic
      hormone. Finally, the HPA-axis response to peripheral or intracerebroventricular
      administration of dexamethasone did not suggest that wheel running increases HPA
      axis negative feedback through GR-mediated mechanisms. Together these findings
      suggest that exercise may promote stress resilience in part by insuring a more
      rapid and shortened HPA response to a stressor thus affecting overall exposure to
      the potentially negative effects of more sustained HPA-axis activation. 

PMID- 24280997
TI  - Give me a hi-5! An additional version of the h-index.

PMID- 24280998
TI  - High impact child abuse may predict risk of elevated suicidality during
      antidepressant initiation.
AB  - BACKGROUND: Concerns have emerged that initiation of an antidepressant can lead
      to or exacerbate suicidality. If those more at risk could be identified prior to
      treatment, treatment risk benefit analysis and patient risk management could be
      assisted. AIMS: This study investigated the role of child abuse and ongoing
      emotional impact from abuse on the risk of suicidality during the first week of
      treatment with an antidepressant. The patient sample for this study was drawn
      from one site of a larger pharmacogenetic study. The hypothesis was that subjects
      with high impact child abuse would have greater elevation of suicidality during
      the first week of antidepressant treatment. METHODS: Fifty-one subjects were
      initiated on either venlafaxine (VEN) or escitalopram (ESC) for major depressive
      disorder (MDD) and had pre-treatment suicidality assayed with the reasons for
      living scale (RFLS), which was repeated after one week of treatment. Several
      clinical, demographic and genotype variables were controlled for. The 15-item
      Impact of Event Scale (IES-15) was administered to subjects reporting abuse to
      dichotomise the abuse group into low and high (IES-15 >= 26) impact groups for
      sub-analysis as per the scales validated rating guidelines. RESULTS: Subjects
      reporting no child abuse exposure were less likely to have increased suicidality
      during the first week of antidepressant treatment (7.6%) compared to subjects
      with low impact abuse (38.5%, p = 0.041) and high impact abuse (58.3%, p =
      0.009). Only high impact abuse predicted increased suicidality after adjustment
      for potential confounders such as depression severity (OR = 31.5, 95% CI = 1.3 to
      748.7, p = 0.03). CONCLUSIONS: If these findings are replicated in larger
      samples, child abuse history could become an important element of assessing risk
      benefit balance when initiating antidepressants and may help guide the level of
      patient review needed during antidepressant initiation.

PMID- 24280999
TI  - Long-term effect of a nurse-led psychosocial intervention on health-related
      quality of life in patients with head and neck cancer: a randomised controlled
      trial.
AB  - BACKGROUND: Head and neck cancer (HNC) patients are prone to have a poor health
      related quality of life after cancer treatment. This study investigated the
      effect of the nurse counselling and after intervention (NUCAI) on the health
      related quality of life and depressive symptoms of HNC patients between 12 and 24
      months after cancer treatment. METHODS: Two hundred and five HNC patients were
      randomly allocated to NUCAI (N=103) or usual care (N=102). The 12-month nurse-led
      NUCAI is problem-focused and patient-driven and aims to help HNC patients manage
      with the physical, psychological and social consequences of their disease and its
      treatment. Health-related quality of life was evaluated with the EORTC QLQ-C30
      and QLQ H&N35. Depressive symptoms were evaluated with the CES-D. RESULTS: At 12
      months the intervention group showed a significant (P<0.05) improvement in
      emotional and physical functioning, pain, swallowing, social contact, mouth
      opening and depressive symptoms. At 18 months, global quality of life, role and
      emotional functioning, pain, swallowing, mouth opening and depressive symptoms
      were significantly better in the intervention group than in the control group,
      and at 24 months emotional functioning and fatigue were significantly better in
      the intervention group. CONCLUSION: The NUCAI effectively improved several
      domains of health-related quality of life and depressive symptoms in HNC patients
      and would seem a promising intervention for implementation in daily clinical
      practice.

PMID- 24281000
TI  - Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a
      potential druggable target for ovarian cancer.
AB  - BACKGROUND: Aberrant choline metabolism has been proposed as a novel cancer
      hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an
      altered MRS-choline profile, characterised by increased phosphocholine (PCho)
      content to which mainly contribute over-expression and activation of choline
      kinase-alpha (ChoK-alpha). METHODS: To assess its biological relevance, ChoK
      alpha expression was downmodulated by transient RNA interference in EOC in vitro
      models. Gene expression profiling by microarray analysis and functional analysis
      was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced
      cells, then validated by in vitro experiments. RESULTS: In silenced cells,
      compared with control, we observed: (I) a significant reduction of both CHKA
      transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop
      in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy
      analysis; (III) a 35-36% of cell growth inhibition, with no evidences of
      apoptosis or modification of the main cellular survival signalling pathways; (IV)
      476 differentially expressed genes, including genes related to lipid metabolism.
      Ingenuity pathway analysis identified cellular functions related to cell death
      and cellular proliferation and movement as the most perturbed. Accordingly, CHKA
      silenced cells displayed a significant delay in wound repair, a reduced migration
      and invasion capability were also observed. Furthermore, although CHKA silencing
      did not directly induce cell death, a significant increase of sensitivity to
      platinum, paclitaxel and doxorubicin was observed even in a drug-resistant
      context. CONCLUSION: We showed for the first time in EOC that CHKA downregulation
      significantly decreased the aggressive EOC cell behaviour also affecting cells'
      sensitivity to drug treatment. These observations open the way to further
      analysis for ChoK-alpha validation as a new EOC therapeutic target to be used
      alone or in combination with conventional drugs.

PMID- 24281001
TI  - p53-dependent and p53-independent anticancer effects of different histone
      deacetylase inhibitors.
AB  - BACKGROUND: Histone deacetylase inhibitors (HDACi) are promising antineoplastic
      agents, but their precise mechanisms of actions are not well understood. In
      particular, the relevance of p53 for HDACi-induced effects has not been fully
      elucidated. We investigated the anticancer effects of four structurally distinct
      HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116
      colon cancer cell lines differing in p53 status. METHODS: Effects were assessed
      by MTT assay, flow-cytometric analyses of propidium iodide uptake, mitochondrial
      depolarisation and cell-cycle distribution, as well as by gene expression
      profiling. RESULTS: Vorinostat was equally effective in p53 wild-type and null
      cells, whereas entinostat was less effective in p53 null cells. Histone
      deacetylase inhibitors treatment suppressed the expression of MDM2 and increased
      the abundance of p53. Combination treatments showed that vorinostat enhanced the
      cytotoxic activity of TRAIL and bortezomib, independent of the cellular p53
      status. Investigations into the effects of an inhibitor of the sirtuin class of
      HDAC, tenovin-1, revealed that tenovin-1-mediated cell death hinged on p53.
      CONCLUSION: These results demonstrate that vorinostat activates p53, but does not
      require p53 for inducing its anticancer action. Yet they also demonstrate that
      entinostat-induced cytotoxic effects partially depend on p53, indicating that
      different HDACi have a different requirement for p53.

PMID- 24281003
TI  - PA28gamma emerges as a novel functional target of tumour suppressor microRNA-7 in
      non-small-cell lung cancer.
AB  - BACKGROUND: MicroRNA-7 (miR-7) has been reported to be a tumour suppressor gene.
      However, whether it has a role in the growth of non-small-cell lung cancer
      (NSCLC) and what is its target involved in the tumour growth is still under
      investigation. METHODS: NSCLC tissue sample, NSCLC cell lines and tissue
      microarray were investigated in this study. Total RNA, miRNA and protein were
      used for RT-PCR and western blot analysis. Immunohistochemistry was performed in
      tissues microarray. Cell culture and intervention experiments were performed in
      vitro and in vivo. Bioinformatics prediction, western blot and luciferase assay
      were identified the target of miR-7. RESULTS: In this study, we found that the
      expression of miR-7 was significantly downregulated not only in NSCLC cell lines,
      but also in human NSCLC tissues compared with the matched adjacent tissues.
      Restoration of its expression through miR-7 mimics in A549 and H1299 NSCLC cells
      inhibited cell proliferation, colony formation, and cell-cycle progression in
      vitro. More importantly, the tumorigenicity in nude mice was reduced after
      administration of miR-7 in vivo. In advance, through bioinformatic analysis,
      luciferase assay and western blot, we identified a novel target of miR-7,
      PA28gamma (a proteasome activator) to be enrolled in the regulation with tumour.
      PA28gamma mRNA and protein levels are markedly upregulated in NSCLC cell lines
      and tumour samples, exhibiting a strong inverse relation with that of miR-7. In
      addition, knockdown of PA28gamma induced similar effects as overexpression of miR
      7 in NSCLC cells. Furthermore, miR-7 overexpression or silencing of PA28gamma
      reduced the cyclinD1 expression at mRNA and protein level in NSCLC cell lines.
      CONCLUSION: All these findings strongly imply that the overexpression of
      PA28gamma resulted from miR-7 downexpression in NSCLC has an important role in
      promoting cancer cell progress and consequently results in NSCLC growth. Thus,
      strategies targeting PA28gamma and/or miR-7 may become promising molecular
      therapies in NSCLC treatment.

PMID- 24281002
TI  - MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix
      metalloproteinase 2 and E-cadherin via KLF4.
AB  - BACKGROUND: Growing evidence suggests that miR-29a has an important role in
      regulating tumourigenesis and development of various types of cancer. However,
      the role and the underlying mechanism of miR-29a in colorectal cancer (CRC)
      remain largely unknown. METHODS: MiR-29a targeted gene was identified by the
      luciferase assay and western blot. MiR-29a function was analysed by invasion
      assays and the orthotopic transplantation mouse model. The miR-29a pathway was
      assayed by real-time PCR, western blot and chip analysis. RESULTS: KLF4 was
      identified as a direct target gene of miR-29a. MiR-29a promoted CRC cell
      invasion, which was blocked by re-expression of KLF4. In addition, MMP2 was
      identified as a novel direct target of KLF4. Both miR-29a overexpression and KLF4
      knockdown promoted MMP2 expression but inhibited E-cadherin expression.
      Furthermore, clinical data indicated that both miR-29a high expression and KLF4
      mRNA low expression were associated with metastasis and poor prognosis in CRC
      patients, and KLF4 protein expression was inversely correlated with MMP2 but
      positively correlated with E-cad protein expression. CONCLUSION: Increased
      expression of miR-29a promoted CRC metastasis by regulating MMP2/E-cad through
      direct targeting KLF4, which highlights the potential of the miR-29a inhibitor as
      a novel agent against CRC metastasis.

PMID- 24281004
TI  - Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard
      dose weekly paclitaxel for patients with previously treated advanced gastric
      cancer.
AB  - BACKGROUND: This randomised phase II trial compared dose-escalated weekly
      paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated
      advanced gastric cancer (AGC). METHODS: Ninety patients were randomised to a
      standard dose of wPTX (80 mg m(-2)) or an escalated dose of wPTX (80-120 mg m(
      2)) to assess the superiority of overall survival (OS) with a one-sided alpha
      error of 0.3 and a power of 0.8. RESULTS: The median OS showed a trend towards
      longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR),
      0.75; one-sided P=0.12), although it was statistically not significant. The
      median progression-free survival (PFS) was significantly longer in the dose
      escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was
      30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of
      all grades of neutropenia was significantly higher with dose escalation (88.7% vs
      60.0%, P=0.002); however, no significant difference was observed in the
      proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34).
      CONCLUSION: Dose-escalated wPTX in patients with pretreated AGC met our
      predefined threshold of primary end point, OS (P<0.3); however, it did not show a
      significantly longer OS. Progression-free survival was significantly better with
      dose escalation.

PMID- 24281005
TI  - Intracellular patterns of sialophorin expression define a new molecular
      classification of breast cancer and represent new targets for therapy.
AB  - BACKGROUND: Sialophorin is a transmembrane sialoglycoprotein. Normally, the
      molecule is only produced by white blood cells where it regulates functions such
      as intercellular adhesion, intracellular signalling, apoptosis, migration and
      proliferation. METHODS: Normal breast tissue and primary breast tumours were
      analysed by immunohistochemistry for sialophorin expression. The sialophorin
      positive breast cancer cell line MCF7 was engineered to stably express either non
      targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then
      performed in vitro to assess apoptosis, intracellular adhesion, transendothelial
      migration and cytotoxicity. An orthotopic mouse model assayed ability to produce
      tumours in vivo. RESULTS: Normal breast epithelial cells exhibit expression of
      the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The
      majority of these normal cells are also negative for expression of the C-terminal
      domain. In contrast, malignant breast epithelial cells exhibit N-terminal
      expression both in the cytoplasm and nucleus and the majority express the C
      terminus in the nucleus. Using differential patterns of intracellular expression
      of the N and C termini of sialophorin, we define six subtypes of breast cancer
      that are independent of histological and receptor status classification.
      Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line
      exhibiting increased homotypic adhesion, decreased transendothelial migration,
      increased susceptibility to apoptosis, increased vulnerability to lysis by
      natural killer cells and decreased ability to produce tumours in mice.
      CONCLUSION: Our results indicate that intracellular patterns of sialophorin
      expression define a new molecular classification of breast cancer and that
      sialophorin represents a novel therapeutic target.

PMID- 24281006
TI  - Gemcitabine enhances the efficacy of reovirus-based oncotherapy through anti
      tumour immunological mechanisms.
AB  - BACKGROUND: Reovirus preferentially infects and kills cancer cells and is
      currently undergoing clinical trials internationally. While oncolysis is the
      primary mode of tumour elimination, increasing evidence illustrates that reovirus
      additionally stimulates anti-tumour immunity with a capacity to target existing
      and possibly relapsing cancer cells. These virus-induced anti-tumour immune
      activities largely determine the efficacy of oncotherapy. On the other hand, anti
      viral immune responses can negatively affect oncotherapy. Hence, the strategic
      management of anti-tumour and anti-viral immune responses through complementary
      therapeutics is crucial to achieve the maximum anti-cancer benefits of
      oncotherapy. METHODS: Intra-peritoneal injection of mouse ovarian surface
      epithelial cells (ID8 cells) into wild-type C57BL/6 mice was treated with a
      therapeutic regimen of reovirus and/or gemcitabine and then analysed for
      prolonged survival, disease pathology, and various immunological parameters.
      Furthermore, in vitro analyses were conducted to assess apoptosis, viral spread,
      and viral production during reovirus and/or gemcitabine treatment. RESULTS: We
      demonstrate that reovirus and gemcitabine combination treatment postpones
      peritoneal carcinomatosis development and prolongs the survival of cancer-bearing
      hosts. Importantly, these anti-cancer benefits are generated through various
      immunological mechanisms, including: (1) inhibition of myeloid-derived suppressor
      cells recruitment to the tumour microenvironment, (2) downmodulation of pro-MDSC
      factors, and (3) accelerated development of anti-tumour T-cell responses.
      CONCLUSION: The complementation of reovirus with gemcitabine further potentiates
      virus-initiated anti-cancer immunity and enhances the efficacy of oncotherapy. In
      the context of ongoing clinical trials, our findings represent clinically
      relevant information capable of enhancing cancer outcomes.

PMID- 24281007
TI  - A preliminary comparison of three dermal exposure sampling methods: rinses, wipes
      and cotton gloves.
AB  - Several methods exist to estimate dermal exposure and it is unclear how
      comparable they are. These methods fall into three main categories: (i) removal
      techniques (such as wiping or rinsing); (ii) interception techniques (such as
      gloves, patches, or coveralls); and (iii) fluorescent tracer techniques.
      Controlled experiments were conducted to compare two removal methods for exposure
      to particulate, and a removal method with an interception method for exposure to
      liquids. Volunteers' hands were exposed to three liquid solutions (glycerol-water
      solutions of different concentrations) and three particulates (Epsom salts,
      calcium acetate and zinc oxide) in simulated exposure scenarios. Both hands were
      exposed and a different sampling method was used on each to allow comparison of
      methods. Cotton glove samplers and a cotton wipe sampling method were compared
      for exposure to liquids. For exposure to powders a cotton wipe sampling method
      was compared to rinsing the hands in deionised water. Wipe and rinse methods
      generally yielded similar results for Epsom salts and zinc oxide (geometric mean
      [GM] ratios of wipe-to-rinse measurements of 0.6 and 1.4, respectively) but they
      did not for calcium acetate (GM wipe-to-rinse ratio of 4.6). For glycerol
      solutions measurements from the glove samplers were consistently higher than wipe
      samples. At lower levels of exposure the relative difference between the two
      methods was greater than at higher levels. At a hand loading level of 24,000 MUg
      cm(-2) (as measured by wiping) the glove-to-wipe ratio was 1.4 and at a hand
      loading of 0.09 MUg cm(-2) the ratio was 42.0. Wipe and rinse methods may be
      directly comparable but the relationship between glove and wipe sampling methods
      appears to be complex. Further research is necessary to enable conversion of
      exposure measurements from one metric to another, so as to facilitate more
      reliable risk assessment.

PMID- 24281008
TI  - Outcome of single pediatric deceased donor renal transplantation to adult kidney
      transplant recipients.
AB  - INTRODUCTION: In times of organ shortage more kidneys were transplanted in
      'expanded criteria kidney' programs. This study examines the outcome of adult
      kidney recipients from pediatric donors. MATERIALS AND METHODS: This single
      center retrospective analysis evaluated eight adult patients who received a
      kidney from a deceased pediatric donor (age 5-17) between 06/2000 and 09/2011.
      RESULTS: The median donor age was 14 years (range 5-17). The median recipient age
      was 49 years (range 25-57). The median cold ischemia time was 13.3 h (range 4.3
      20.1), while the median warm ischemia time was 53 min (range 42-60). The median
      follow-up was 35.8 months (range 7-142). Acute rejection was observed in 50.0% of
      cases. The median HLA mismatch was 2.0. The median 1-year creatinine level was
      0.95 mg/dl, the uncensored 1-year graft survival was 75.0% and the 3-year graft
      survival 62.5%, respectively. No recipient died within the follow-up period. As
      severe surgical complications, one stenosis of the renal artery and one
      lymphocele needing surgical revision were observed. CONCLUSIONS: Renal
      transplantation of a deceased single pediatric donor to an adult recipient can be
      performed safely and shows a good outcome. Wherever feasible, single pediatric
      kidney transplantation can double the number of recipients over an 'en-bloc'
      transplantation. The price for a single pediatric kidney transplant may be a
      higher vascular complication rate and a higher rejection risk. Despite the higher
      risks, transplantation of a single pediatric donor kidney should be performed
      when accomplishable.

PMID- 24281009
TI  - Assessment of the noise-protective action of the olivocochlear efferents in
      humans.
AB  - It has been demonstrated in different mammals that the medial olivocochlear
      efferents (MOC) exert a noise-protective effect on the cochlea. In humans such an
      effect has not unambiguously been shown as of yet. The objective of this study
      was to assess the relationship between MOC activity and susceptibility of the
      cochlea to noise-induced hearing loss in humans. In 40 normally hearing human
      subjects, we measured the following: (1) magnitude of temporary threshold shift
      (TTS) after exposure to 60 min broadband noise of 94 dB SPL and (2) contralateral
      suppression (CS) of distortion product otoacoustic emissions (which reflects MOC
      activity) using two different measurement paradigms. CS was measured in duplicate
      on 2 measurement days. The relationship between TTS and CS was assessed.
      Individual TTS in the most affected frequencies (4 > 3 > 8 kHz) ranged from 9 to
      28 dB HL, with an average maximum TTS of 18.4 dB HL. The amount of CS ranged
      between 0.3 and 3 dB. The repeatability of CS, evaluated by Cronbach's alpha
      value, ranged from 0.76 (acceptable repeatability) to 0.86 (good repeatability).
      One of the two different measurement paradigms showed a statistically significant
      inverse correlation between CS magnitude and amount of TTS, which was
      hypothesized. This is the first study on the relationship between TTS and CS in
      humans employing TTS induced under controlled laboratory conditions and two
      different MOC paradigms. The findings are compatible with the hypothesis that MOC
      activity is noise protective in humans. Future perspectives include modified CS
      paradigms, longitudinal cohort studies or efforts to also monitor lateral
      efferent effects in humans.

PMID- 24281011
TI  - pH and amine-induced various octamolybdate-based metal-organic complexes:
      assembly, structures and properties.
AB  - Three octamolybdate-based metal-organic complexes (MOCs), namely,
      [H2en]2[Cu(pzca)2(Mo8O26)].4H2O (1), [Cu2(pzca)2(Mo8O26)0.5(H2O)4].H2O (2) and
      [Cu(I)3Cu(II)4(pzca)7(Mo8O26)(H2O)2].4H2O (3) (en = ethylenediamine, pzca = 2
      pyrazinecarboxylic acid), have been successfully synthesized under hydrothermal
      conditions via adding different kinds of amine and adjusting the pH values. The
      single crystal X-ray diffraction, elemental analyses, IR spectra, and
      thermogravimetric analyses have been used to characterize the title complexes. In
      compound 1, the [Cu(pzca)2] units bridge the [beta-Mo8O26](4-) clusters to
      generate a 1D chain, which is extended by hydrogen-bonding interactions to a 3D
      supramolecular structure. Compound 2 exhibits a 3D coordination framework based
      on the 1D infinite [Cu2(pzca)2]n(2n+) zigzag chains and beta-Mo8O26(4-) anions,
      and shows a trinodal 3,3,4-connected {8(3)}4{8(6)} topology containing a
      dodecagonal channel with the dimension of 13.496 * 19.642 A(2). Compound 3 is a
      3D metal-organic network derived from the "lambda"-like [Cu5(pzca)4] subunits and
      [beta-Mo8O26](4-) anions, which represents a novel
      {4.6.8(3).10}2{4.6.8}2{4(2).10(4)}{4(2).8(3).10}{6.8(2)}2{6(2).10(3).12}{6(2).8(2
      .10(2)}{6(2).8(3).10}{6(3)}4 topology in octamolybdate-based MOCs. The structural
      diversities show that the different amines and pH value of the reaction system
      play key roles in the construction of high dimensional architectures. Moreover,
      the electrochemical behaviors and photocatalytic activity for compound 1 have
      been investigated in detail.

PMID- 24281012
TI  - Chronic liver diseases and hepatocellular carcinoma: an update for 2013.

PMID- 24281013
TI  - Clinical and histological features of different types of Budd-Chiari syndrome: a
      comparison of 4 cases.
AB  - Budd-Chiari syndrome (BCS) is a rare condition characterized by hepatic venous
      outflow obstruction. In this report, we present 4 cases of BCS with complete and
      incomplete obstruction of the inferior vena cava (IVC) and hepatic vein (HV).
      Each case showed different and unique features of liver damage, which were
      attributed to the site and degree of obstruction. Interestingly, improved liver
      functions such as increased serum albumin levels, decreased hyaluronic acid
      levels and a normal indocyanine green clearance test were evident within 1 month
      of the balloon angioplasty. Pericellular fibrosis and hypervascular regenerative
      nodules were also reversible after obstruction removal. Therefore, it is very
      important to manage this rare disease before it progresses to liver cirrhosis.

PMID- 24281014
TI  - Autoimmune hepatitis and immunoglobulin G4-associated autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a disease that is characterized by the presence of
      autoantibodies and elevated levels of serum immunoglobulin G (IgG) and hepatic
      enzymes. Its characteristic findings in the liver include interface hepatitis,
      infiltration of lymphocytes and plasma cells, and rosette formation, and is
      treated with immunosuppressive drugs. Autoimmune pancreatitis, a pancreatic
      disease caused by an autoimmune mechanism, is associated with elevated levels of
      serum IgG4 and the infiltration of IgG4-positive cells into the pancreatic
      parenchyma, and it is occasionally accompanied by systemic features. This
      systemic inflammatory disease characterized by the infiltration of IgG4-positive
      plasma cells and elevated serum IgG4 levels was recently classified as an IgG4
      related disease. A few studies have reported AIH cases with infiltrated IgG4
      positive plasma cells in the liver, suggesting the involvement of IgG4 in the
      pathogenesis of AIH. This feature was called IgG4-associated AIH and only two
      studies have been published. However, the diagnostic criteria of IgG4-associated
      AIH has not been defined and the epidemiology and clinical features remain
      uncertain. The degree of IgG4-positive plasma cell infiltration in the liver was
      different in each article. The serum IgG4 level was not elevated in one study,
      whereas it was severely elevated in the other. Corticosteroid therapy normalized
      liver enzymes in both studies. Further studies are needed to define the
      epidemiological features or diagnostic criteria.

PMID- 24281010
TI  - Insulin signaling, resistance, and the metabolic syndrome: insights from mouse
      models into disease mechanisms.
AB  - Insulin resistance is a major underlying mechanism responsible for the 'metabolic
      syndrome', which is also known as insulin resistance syndrome. The incidence of
      the metabolic syndrome is increasing at an alarming rate, becoming a major public
      and clinical problem worldwide. The metabolic syndrome is represented by a group
      of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and
      hypertension. It is also a significant risk factor for cardiovascular disease and
      increased morbidity and mortality. Animal studies have demonstrated that insulin
      and its signaling cascade normally control cell growth, metabolism, and survival
      through the activation of MAPKs and activation of phosphatidylinositide-3-kinase
      (PI3K), in which the activation of PI3K associated with insulin receptor
      substrate 1 (IRS1) and IRS2 and subsequent Akt->Foxo1 phosphorylation cascade has
      a central role in the control of nutrient homeostasis and organ survival. The
      inactivation of Akt and activation of Foxo1, through the suppression IRS1 and
      IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and
      overnutrition, may act as the underlying mechanisms for the metabolic syndrome in
      humans. Targeting the IRS->Akt->Foxo1 signaling cascade will probably provide a
      strategy for therapeutic intervention in the treatment of type 2 diabetes and its
      complications. This review discusses the basis of insulin signaling, insulin
      resistance in different mouse models, and how a deficiency of insulin signaling
      components in different organs contributes to the features of the metabolic
      syndrome. Emphasis is placed on the role of IRS1, IRS2, and associated signaling
      pathways that are coupled to Akt and the forkhead/winged helix transcription
      factor Foxo1. 

PMID- 24281015
TI  - Factors of response to pegylated interferon/ribavirin combination therapy and
      mechanism of viral clearance.
AB  - OBJECTIVES: This study explores viral factors of the interferon (IFN) and
      ribavirin (RBV) resistance-determining region (IRRDR), the IFN sensitivity
      determining region (ISDR) and the core protein, and host factor interleukin 28B
      associated with response to pegylated IFN (PEG-IFN) and RBV combination therapy,
      and the correlation of viral and host factors with IFN-lambda1. METHODS: A total
      of 58 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. The
      pretreatment factors associated with rapid virological response (RVR) and
      sustained virological response (SVR) were analyzed. Pretreatment IFN-lambda1
      serum levels were compared with the viral and host factors. RESULTS: Univariate
      analysis showed that IRRDR >=6 and ISDR >=2 were significant pretreatment
      predictors of RVR, and multivariate analysis identified IRRDR >=6 and hemoglobin
      as significant predictors of SVR. Pretreatment IFN-lambda1 was significantly
      higher in the SVR group than in the non-SVR group and also in the IRRDR >=6 group
      than in the IRRDR <=5 group. CONCLUSIONS: IRRDR >=6 was the only significant
      predictor of SVR and was correlated with IFN-lambda1. High serum levels of IFN
      lambda1 may be conducive to effective PEG-IFN/RBV combination therapy because of
      the immunomodulatory system.

PMID- 24281016
TI  - Prediction of response to pegylated interferon/ribavirin combination therapy for
      chronic hepatitis C genotypes 2a and 2b and high viral load.
AB  - OBJECTIVE: We investigated the impact of host genetics represented by the single
      nucleotide polymorphism (SNP) of the IL28B gene and viral genetic variations
      within the nonstructural protein 5A (NS5A) [including the interferon
      (IFN)/ribavirin (RBV) resistance-determining region (IRRDR) and the IFN
      sensitivity-determining region (ISDR)] on the outcome of pegylated IFN and RBV
      (PEG-IFN/RBV) treatment. METHODS: Sixty-six patients infected with hepatitis C
      virus (HCV)-2a or HCV-2b who received PEG-IFN/RBV for 24 weeks were examined.
      RESULTS: In HCV-2a, the major genotype of IL28B SNP showed a tendency toward
      association with sustained virological response (SVR) and rapid virological
      response (RVR), and four or more mutations in IRRDR (IRRDR[2a] >=4) and one or
      more mutations in ISDR plus its carboxyl-flanking region (ISDR/+C[2a] >=1) were
      significantly associated with SVR and RVR. In HCV-2b, one or more mutations in
      the N-terminal part of IRRDR (IRRDR/N[2b] >=1) were significantly associated with
      RVR. Multivariate analysis identified the major genotype of IL28B SNP and
      IRRDR[2a] >=4 as independent predictive factors of SVR in HCV-2a, with IRRDR[2a]
      >=4 being more powerful than the IL28B SNP. Also, IRRDR[2a] >=4 in HCV-2a and
      IRRDR/N[2b] >=1 in HCV-2b were significant determiners of RVR. CONCLUSION: The
      NS5A sequence heterogeneity and IL28B SNP are useful factors to predict the
      sensitivity to PEG-IFN/RBV therapy in HCV-2a and HCV-2b infections.

PMID- 24281017
TI  - Outcome of double-filtration plasmapheresis plus interferon treatment in
      nonresponders to pegylated interferon plus ribavirin combination therapy.
AB  - OBJECTIVES: We assessed the outcome of double-filtration plasmapheresis (DFPP)
      combined with pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in
      patients infected with hepatitis C virus (HCV)-1b whose HCV had not disappeared
      during PEG-IFN/RBV combination therapy, or who had relapsed after the end of the
      therapy. Additionally, we investigated factors predictive of sustained
      virological response (SVR), including host and viral genetic factors, to DFPP
      plus IFN/RBV therapy. METHODS: A total of 40 patients infected with HCV-1b whose
      HCV virus had not been eradicated by previous PEG-IFN/RBV therapy were enrolled
      for treatment by DFPP plus IFN/RBV. Rapid virological response (RVR) and SVR were
      assessed, and pretreatment factors associated with SVR - the interleukin (IL)28B
      gene, the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity
      determining region (ISDR) - were analyzed. RESULTS: Of the 40 patients, 9 (23%)
      achieved RVR and 10 (25%) achieved SVR. The significant factors associated with
      SVR were IL28B major and RVR, as assessed by multivariate analysis (p = 0.0182, p
      = 0.0005). CONCLUSION: Patients whose HCV is not eradicated by previous PEG
      IFN/RBV would be good candidates for combined DFPP and IFN/RBV retreatment
      provided they demonstrate IL28B major and have achieved RVR.

PMID- 24281018
TI  - Hypothermia protects against fulminant hepatitis in mice by reducing reactive
      oxygen species production.
AB  - OBJECTIVE: Mild hypothermia (32-33 degrees C) shows protective effects in
      patients with brain damage and cardiac arrest. Although cold-inducible RNA
      binding protein (CIRP) contributes to the protective effects of hypothermia
      through extracellular signal-regulated kinase activation in fibroblasts, the
      effects of hypothermia in the liver remain unclear. METHODS: We analysed the
      effects of cold temperature on fulminant hepatitis, a potentially fatal disease,
      using the D-galactosamine (GalN)/lipopolysaccharide (LPS) and concanavalin (con)
      A-induced hepatitis models in mice. After GalN/LPS administration and
      anaesthesia, mice in the hypothermia group were kept at 25 degrees C and those in
      control group were kept at 35 degrees C. After concanavalin A (con A)
      administration, the mice in the hypothermia group were placed in a chamber with
      an ambient temperature of 6 degrees C for 1.5 h. RESULTS: Hypothermia attenuated
      liver injury and prolonged survival. Activation of c-Jun N-terminal kinase and
      Akt, which are involved in reactive oxygen species (ROS) accumulation, was
      suppressed by low temperature. Hypothermia significantly decreased oxidized
      protein levels, and treatment with N-acetyl-L-cysteine, an antioxidant,
      attenuated GalN/LPS-induced liver injury. In con A-induced hepatitis, CIRP
      expression was upregulated and Bid expression was downregulated, resulting in
      decreased apoptosis of hepatocytes in the hypothermia group. CONCLUSIONS: These
      data suggest that hypothermia directly protects hepatocytes from cell death via
      reduction of ROS production in fulminant hepatitis.

PMID- 24281019
TI  - Oxidative stress and epigenetic instability in human hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer death, and its
      development is influenced by the status of inflammation and oxidative stress in
      the liver. Although oxidative stress might induce genetic changes and play a role
      in HCC development, many epigenetic alterations have also been reported in this
      type of tumor, suggesting the importance of epigenetic instability in
      hepatocarcinogenesis. Epigenetic instability results in 2 types of DNA
      alterations: hypermethylation of the promoter of tumor suppressor genes (TSGs),
      and hypomethylation of nonpromoter CpG, such as repetitive elements and satellite
      DNA. The former causes transcriptional inactivation of TSGs, while the latter
      reportedly induces chromosomal instability and an abnormal activation of
      oncogenes as well as mobile genetic elements. Oxidative stress could induce
      epigenetic instability and inactivate TSGs through the recruitment of the
      polycomb repressive complex to the promoter sequence carrying DNA damage induced
      by oxidation. Inflammatory cytokines from immune cells also reportedly induce
      expression of several histone and DNA modulators. On the other hand, DNA
      oxidation could lead to activation of DNA repair pathways and affect the binding
      of methyl cytosine-binding protein to DNA, which could cause DNA hypomethylation.
      The decrease of the level of methyl group donors also contributes to the
      alteration in the methylation status. These mechanisms should act in concert and
      induce epigenetic instability, leading to HCC.

PMID- 24281020
TI  - Novel mouse models of hepatocarcinogenesis with stepwise accumulation of genetic
      alterations.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide.
      Various risk factors are involved in hepatocarcinogenesis. Among them, chronic
      inflammation, including chronic hepatitis and cirrhosis mainly caused by
      hepatitis B virus and/or hepatitis C virus infection, plays an important role in
      HCC development. On the other hand, comprehensive genetic analyses of HCC using
      whole genome and exome sequencing revealed that cancer cells possess a large
      number of somatic mutations, suggesting that a wide variety of genetic
      alterations and the resultant dysregulated molecular pathways contribute to the
      development of HCC. Activation-induced cytidine deaminase (AID) is a nucleotide
      editing enzyme, and aberrant expression of AID induced by inflammatory responses
      contributes to hepatocarcinogenesis via the accumulation of genetic alterations
      in various tumor-related genes. Constitutive expression of AID in hepatocyte
      lineage cells provides novel mouse models that recapitulate the tumorigenesis of
      human HCC through stepwise accumulation of genetic alterations.

PMID- 24281021
TI  - Reactive oxygen species induce epigenetic instability through the formation of 8
      hydroxydeoxyguanosine in human hepatocarcinogenesis.
AB  - Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the
      emergence of hepatocellular carcinoma (HCC). We previously reported that tumor
      suppressor gene (TSG) methylation is a critical factor during the early stages of
      hepatocarcinogenesis. In this study, we clarify the association between oxidative
      stress and epigenetic alterations during hepatocarcinogenesis. We examined DNA
      oxidation and methylation profiles in 128 liver biopsy samples from CHC patients.
      The DNA oxidation and methylated TSG numbers were quantified using
      immunohistochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and quantitative
      PCR for 11 TSGs, respectively. The quantitative chromatin immunoprecipitation-PCR
      (ChIP-qPCR) assay in HepG2 and fetal liver Hc cells treated with H2O2 was used to
      quantify trimethyl-H3K4, acetylated-H4K16 (an active chromatin marker), trimethyl
      H3K27 (a repressive chromatin marker) and 8-OHdG. We analyzed 30 promoters of 25
      different TSGs by qPCR. The high levels of 8-OHdG was the only variable that was
      significantly associated with the increased number of methylated TSGs in CHC (p <
      0.0001). The ChIP-qPCR revealed that after H2O2 treatment of the cell lines, the
      8-OHdG-bound promoters showed a modification from an active chromatin (trimethyl
      H3K4 and acetylated-H4K16 dominant) to a repressive chromatin (trimethyl-H3K27
      dominant) status. We conclude that oxidative stress alters the chromatin status,
      which leads to abnormal methylation of TSGs, and contributes to
      hepatocarcinogenesis in CHC patients.

PMID- 24281022
TI  - CD34 expression in noncancerous liver tissue predicts multicentric recurrence of
      hepatocellular carcinoma.
AB  - BACKGROUND: Metachronous multicentric recurrence of hepatocellular carcinoma
      (HCC) is a common cause of morbidity and mortality following curative surgical
      resection. Clinical and laboratory predictors of these processes can markedly aid
      in managing these patients. Capillarization of hepatic sinusoids is also a well
      known phenomenon in many liver diseases, especially in neoplastic liver diseases.
      Here, we investigated the clinical features, fibrosis scores and distribution of
      CD34 in noncancerous hepatic tissues of postresection patients with and without
      multicentric recurrence. METHODS: Eighteen patients with multicentric recurrence
      of HCC diagnosed by histological examination of repeated hepatectomy specimens
      and 72 HCC patients with more than 5-year disease-free survival postresection
      participated in the study. We compared the clinicopathological features of these
      two groups. We examined noncancerous hepatic tissues for iron deposition by
      Prussian blue staining and computed the CD34-labeling index (LI) through
      immunohistochemistry using anti-CD34 antibody. RESULTS: CD34-LI was significantly
      higher in the multicentric recurrence group (p < 0.001) and staging scores of
      fibrosis were also significantly higher in the recurrence group (p = 0.035). A
      high histological activity grade (p = 0.057) and a high alanine aminotransferase
      level (p = 0.060) were also associated with recurrence. There were no significant
      differences between the two groups in age, sex, hepatitis B virus surface antigen
      and anti-hepatitis C virus antibody levels, or grade of iron deposition. On
      multivariate analysis, high CD34-LI was the only independent risk factor (p =
      0.001) for metachronous multicentric recurrence. CONCLUSION: CD34 expression in
      the capillaries and sinusoids of noncancerous hepatic tissue is a risk factor for
      multicentric recurrence of HCC. Histologic assessment of hepatic tissue with CD34
      immunohistochemistry might be useful for the prognostic evaluation of HCC
      patients after surgery.

PMID- 24281023
TI  - Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image
      of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma:
      a nationwide retrospective study on their natural course and risk factors.
AB  - OBJECTIVE: We aimed to investigate the natural outcome of nonhypervascular
      lesions detected in the hepatobiliary phase of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI by performing a
      longitudinal study retrospectively enrolled in a nationwide manner. METHODS:
      Between February 2008 and March 2011, 224 patients with 504 nodules that were
      diagnosed as nonhypervascular by imaging were recruited from institutions that
      participated in the present study. We examined the natural outcome of
      nonhypervascular lesions and evaluated the risk factors. RESULTS: Of the 504
      nodules, 173 (34.3%) showed hypervascular transformation. The overall cumulative
      incidence of hypervascular transformation was 14.9% at 12 months and 45.8% at 24
      months. Multivariate analysis using the Cox regression model revealed previous
      treatment history for hepatocellular carcinoma (HCC; relative risk = 1.498; p =
      0.036, 95% CI 1.03-2.19) and hyperintensity on T2-weighted images (relative risk
      = 1.724; p = 0.015, 95% CI 1.11-2.67) were identified as independent factors for
      hypervascular transformation. CONCLUSIONS: Patients who have a previous treatment
      history for HCC and with hypointense nodules showing hyperintensity on T2
      weighted images need careful follow-up because of the high incidence of
      hypervascular transformation.

PMID- 24281024
TI  - Radiofrequency ablation for hepatic malignancies: is needle tract cauterization
      necessary for preventing iatrogenic bleeding?
AB  - OBJECTIVE: To evaluate whether iatrogenic hemorrhage can be prevented by
      intrahepatic tract ablation following radiofrequency ablation (RFA) therapy for
      hepatic malignancies. METHODS: A retrospective cohort study analyzing a
      prospective database in a single institution was conducted. The incidence of
      postprocedural complications was compared in two groups: one with cauterization
      of the needle tracts after RFA and the other without. RESULTS: The complication
      rates of intraperitoneal hemorrhage were 1.05% (4/380) and 0.92% (6/652) in the
      nonablation group and the ablation group, respectively (p = 0.90). All of these
      10 patients with iatrogenic bleeding were classified as Child-Pugh grade A. Among
      the 15 hemodialysis patients in this study, hemorrhage was seen in 2 (13.3%),
      compared with 8 (0.79%) of the nonhemodialysis patients (p = 0.0002). There were
      no statistically significant differences in the incidence of other complications
      including pleural effusion, serous ascites, pneumothorax, hemothorax, hepatic
      infarction, bile duct injury and pericardial effusion between the two groups.
      Gastrointestinal perforation, peritonitis or tumor seeding were not observed.
      CONCLUSION: Our study found a high incidence of bleeding after RFA among
      hemodialysis patients. Irrespective of tract ablation being after RFA, iatrogenic
      hemorrhage appeared to be equivalent in this population.

PMID- 24281025
TI  - Usefulness of the extracted-overlay function in CT/MR-ultrasonography fusion
      imaging for radiofrequency ablation of hepatocellular carcinoma.
AB  - OBJECTIVES: We developed a novel technique of the extracted-overlay function in
      CT/MR-ultrasonography (US) fusion imaging for radiofrequency ablation (RFA), in
      which only a tumor extracted from CT/MR images with a virtual ablative margin of
      arbitrary thickness is overlaid on US. The usefulness of this function is
      investigated in this preliminary report. METHODS: The volume data of the
      extracted tumor with a virtual ablative margin were created on an image
      processing workstation, and transported into a US unit equipped with a CT/MR-US
      fusion imaging system. After the positional registration of US and transported
      images, the extracted tumor with an ablative margin could be overlaid on US. In
      RFA, using this function, an electrode was inserted targeting the overlaid tumor
      with an ablative safety margin of 5 mm on US, and the treatment effect was
      evaluated by dynamic CT. Treatment results of 23 consecutive hepatocellular
      carcinomas (HCCs) that underwent RFA using this function were retrospectively
      analyzed. RESULTS: Complete tumor ablation was achieved in 22 (95.7%) and 1
      (4.3%) HCCs in 1 and 2 treatment sessions, respectively. CONCLUSIONS: Due to the
      visualization of an extracted tumor with an ablative safety margin on a US image,
      even during and after ablation, this function is useful for treatment planning
      and guidance of RFA.

PMID- 24281026
TI  - Hepatocellular carcinoma in Child-Pugh C cirrhosis: prognostic factors and
      survival benefit of nontransplant treatments.
AB  - A retrospective multicenter study was conducted to clarify the survival benefit
      of nontransplant treatments for patients with hepatocellular carcinoma (HCC)
      associated with Child-Pugh C cirrhosis. Data on 436 patients, including 203
      treated patients with HCC, were collected from 20 institutions in Japan. Cox's
      proportional hazards model corrected for bias by propensity score analysis
      clearly showed the following as significant independent prognostic factors,
      including all four nontransplant treatments examined: transarterial
      chemoembolization, hepatic arterial infusion chemotherapy, percutaneous ethanol
      injection therapy, radiofrequency ablation, hepatitis B virus, number of tumors,
      log alpha-fetoprotein, encephalopathy, ascites and prothrombin time. The
      cumulative survival rate was significantly higher in the treated group than in
      the untreated group. The present findings suggest that prognosis can be improved
      by nontransplant treatments in patients with low Child-Pugh scores. Since this
      study was retrospective, the possibility of selection bias cannot be ruled out.
      Therefore, verification by a prospective controlled study is warranted.

PMID- 24281028
TI  - Postablation insufficiency fracture of the iliac crest: management by
      percutaneous screw fixation.

PMID- 24281029
TI  - Novel combinations for the treatment of metastatic breast cancer.
AB  - Anthracyclines and taxanes represent the mainstay of first-line cytotoxic therapy
      for metastatic breast cancer (MBC), but most patients eventually develop
      resistance to these agents. Consequently, alternative combinations for MBC
      therapy are the subject of much ongoing research. Capecitabine and ixabepilone is
      the only chemotherapy combination specifically approved for MBC after failure of
      anthracyclines and taxanes. Other options have limited data to support their use
      in this setting but are commonly used in practice. Future MBC therapies will
      likely combine alternative chemotherapies and novel biologic agents, and numerous
      ongoing trials should help to further define the proper use of these regimens. 

PMID- 24281030
TI  - Number of Axillary Lymph Node Metastases Determined by Preoperative Ultrasound is
      Related to Prognosis in Patients with Breast Cancer.
AB  - OBJECTIVE: To analyze the impact on prognosis of the number of axillary lymph
      node metastases (LNM) detected by ultrasound (US) in patients with breast cancer.
      METHODS: One-to-one comparison of LNM was performed between the ultrasound and
      histologic diagnosis in 380 patients. RESULTS: The accuracy of preoperative
      ultrasound diagnosis was 79.7%. According to the subdivision of number of LNM (0,
      1-3, 4-9, 10+), the accuracy rates associated with LNM were 82%, 49%, 34%, and
      86%, respectively. The disease-free-survival curves according to the number of
      LNM were similar in them. CONCLUSION: Preoperative ultrasound can determine
      axillary involvement and may be useful for predicting prognosis.

PMID- 24281031
TI  - Oxidative stress and exhaled breath analysis: a promising tool for detection of
      lung cancer.
AB  - Lung cancer is one of the few neoplasia in which the principal aetiology is
      known, with cigarette smoke donating a considerable oxidative burden to the
      lungs. This may be part of the aetiology of lung cancer, but the neoplastic
      process is also associated with increased oxidative stress. Nonetheless, it is
      difficult to study the mechanisms behind the induction of lung cancer in smokers,
      but newer techniques of breath analysis targeting markers of oxidative stress and
      anti-oxidant capacity show promise in unravelling some of the pathways. This
      review highlights recent developments in the assessment of oxidative stress by
      non-invasive methods of breath analysis which are becoming powerful research
      techniques with possible clinical applications. 

PMID- 24281032
TI  - Regional Therapy for Recurrent Metastatic Melanoma Confined to the Extremity:
      Hyperthermic Isolated Limb Perfusion vs. Isolated Limb Infusion.
AB  - Melanoma patients with recurrent disease confined to an extremity can be offered
      one of two regional therapies that both give high complete response rates.
      Isolated limb infusion (ILI) is a newer technique performed with catheters and
      tourniquets that has a reduced potential morbidity, decreased efficacy and does
      not treat the regional nodal basin. Hyperthermic Isolated Limb Perfusion (HILP)
      is an open surgical technique that includes removal of the regional nodal basin
      as part of the surgical procedure. An analysis was performed of the rates of
      regional nodal disease in this patient population to determine the percentage of
      patients with stage III metastatic disease to the lymph nodes that would be under
      treated with the ILI technique. A total of 229 patients underwent a HILP for
      melanoma with regional lymph node dissection as is our standard between July 1987
      and December 2009. Ninty-two of the 229 patients (40%) had metastatic regional
      nodal disease documented at the time of the HILP procedure. HILP is the only
      technique that addresses all micrometastatic disease on the extremity. 

PMID- 24281033
TI  - Nutrients and risk of colon cancer.
AB  - Dietary fats are thought to be important in the etiology of colon cancer.
      However, the evidence linking them is inconclusive. Studies on dietary protein,
      cholesterol and carbohydrate and the risk of colon cancer are also inconsistent.
      This study examined the association between dietary intake of protein, fats,
      cholesterol and carbohydrates, and the risk of colon cancer. Mailed
      questionnaires were completed by 1731 individuals with histologically confirmed
      cases of colon cancer and 3097 population controls between 1994 and 1997 in seven
      Canadian provinces. Measurements included socio-economic status, lifestyle habits
      and diet. A 69-item food frequency questionnaire was used to provide data on
      eating habits from two years before the study. Odds ratios (OR) and 95%
      confidence intervals (CI) were computed using unconditional logistic regression.
      The nutrients were categorized by quartiles based on the distributions among the
      controls. Intake of polyunsaturated fat, trans-fat and cholesterol were
      significantly associated with the risk of colon cancer; the ORs for the highest
      quartiles were 1.36 (95% CI, 1.02-1.80), 1.37 (95% CI, 1.10-1.71) and 1.42 (95%
      CI, 1.10-1.84), respectively. The association was stronger with proximal colon
      cancer (PCC). An increased risk was also observed with increasing intake of
      sucrose for both proximal and distal colon cancers; the ORs for the highest
      quartiles were 1.67 (95% CI, 1.22-2.29) for PCC and 1.58 (95% CI, 1.18-2.10) for
      distal colon cancer (DCC). An elevated risk of PCC was also found with increased
      lactose intake. Our findings provide evidence that a diet low in fat and sucrose
      could reduce the risk of various colon cancers. 

PMID- 24281034
TI  - Targeted therapies in epithelial ovarian cancer.
AB  - Molecularly targeted therapy is relatively new to ovarian cancer despite the
      unquestionable success with these agents in other solid tumours such as breast
      and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can
      survive several years on treatment. However chemotherapy diminishes in efficacy
      over time whilst toxicities persist. Newer biological agents that target explicit
      molecular pathways and lack specific chemotherapy toxicities such as
      myelosuppression offer the advantage of long-term therapy with a manageable
      toxicity profile enabling patients to enjoy a good quality of life. In this
      review we appraise the emerging data on novel targeted therapies in ovarian
      cancer. We discuss the role of these compounds in the front-line treatment of
      ovarian cancer and in relapsed disease; and describe how the development of
      predictive clinical, molecular and imaging biomarkers will define the role of
      biological agents in the treatment of ovarian cancer. 

PMID- 24281035
TI  - Angiogenesis and melanoma.
AB  - Angiogenesis occurs in pathological conditions, such as tumors, where a specific
      critical point in tumor progression is the transition from the avascular to the
      vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic
      cells of growth factors specific for endothelial cells, which are able to
      stimulate the growth of the host's blood vessels. This article summarizes the
      literature concerning the relationship between angiogenesis and human melanoma
      progression. The recent applications of antiangiogenic agents which interfere
      with melanoma progression are also described. 

PMID- 24281037
TI  - What is inflammatory breast cancer? Revisiting the case definition.
AB  - The case definition for inflammatory breast cancer (IBC) is controversial. The
      American Joint Committee on Cancer defines IBC as redness, warmth and edema
      involving at least half the breast. The SEER program relies on a pathologic
      finding of dermal lymphatic invasion and recently added those with clinical
      involvement of more than 3/4 of the breast. We established a registry to collect
      information and specimens from IBC patients to clarify the epidemiology and
      biology of these tumors. The goals of this report are to suggest improvements
      regarding case definitions and provide data on the variety of presentations
      relevant to early diagnosis. 

PMID- 24281036
TI  - Overexpression of periostin and lumican in esophageal squamous cell carcinoma.
AB  - To identify biomarkers for early detection for esophageal squamous cell carcinoma
      (ESCC), we previously carried out a genome-wide gene expression profiling study
      using an oligonucleotide microarray platform. This analysis led to identification
      of several transcripts that were significantly upregulated in ESCC compared to
      the adjacent normal epithelium. In the current study, we performed
      immunohistochemical analyses of protein products for two candidates genes
      identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM),
      using tissue microarrays. Increased expression of both periostin and lumican was
      observed in 100% of 137 different ESCC samples arrayed on tissue microarrays.
      Increased expression of periostin and lumican was observed in carcinoma as well
      as in stromal cell in the large majority of cases. These findings suggest that
      these candidates can be investigated in the sera of ESCC patients using ELISA or
      multiple reaction monitoring (MRM) type assays to further explore their utility
      as biomarkers. 

PMID- 24281038
TI  - Increased Level of Phosphorylated ShcA Measured by Chemiluminescence-Linked
      Immunoassay Is a Predictor of Good Prognosis in Primary Breast Cancer Expressing
      Low Levels of Estrogen Receptor.
AB  - The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in
      growth factor receptor signaling. The role of phosphorylated ShcA is to link
      receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus
      facilitating signal transduction from receptor tyrosine kinases to Ras, leading
      to MAPK activation. The present study was designed to investigate the prognostic
      significance of phosphorylated ShcA in primary breast cancer and its association
      in the interactions between the ER and ErbB2 pathways. Using a two-site
      chemiluminescence-linked immunosorbent assay, we detected the quantitative
      expression levels of total tyrosine- and threonine-phosphorylated ShcA in cytosol
      fractions obtained from fresh frozen tissue samples of 153 selected primary
      breast cancer patients. ShcA phosphorylation was not associated with nodal
      status, estrogen receptor (ER) status or grading. High levels of both tyrosine
      (pYShcA) and serine (pSShcA) phosphorylated ShcA correlated with good prognosis
      (p < 0.01), with respect to both disease-free (DFS) and overall survival (OS). In
      addition, pShcA levels were found to correlate with threonine-phosphorylated
      ErbB2 and inversely with phosphorylated Akt (pAkt), as well as ErbB2 and ER
      expression levels. Our findings demonstrate that ShcA activation in primary
      breast cancer patients correlates with low levels of ER, and is associated with
      good prognosis. 

PMID- 24281039
TI  - Biology of human cutaneous melanoma.
AB  - A review of the natural behavior of cutaneous melanoma, clinical and pathological
      factors, prognostic indicators, some basic research and the present and possible
      futuristic strategies in the management of this disease are presented. While
      surgery remains to be the most effective therapeutic approach in the management
      of early primary lesions, there is no standard adjuvant therapy after surgical
      resection, or for metastatic disease. 

PMID- 24281041
TI  - Telmisartan protects against vascular dysfunction with peroxisome proliferator
      activated receptor-gamma activation in hypertensive 5/6 nephrectomized rats.
AB  - BACKGROUND/AIMS: Telmisartan and losartan, angiotensin II type 1 (AT1) receptor
      antagonists, are used to manage hypertension. We previously reported that
      telmisartan, a partial agonist of peroxisome proliferator-activated receptor
      gamma (PPAR-gamma), exhibited stronger vasoprotection than the same dose of
      losartan in normotensive chronic kidney disease (CKD) rats. We investigated
      whether telmisartan could inhibit vascular dysfunction in hypertensive CKD rats,
      via both AT1 receptor blockade and PPAR-gamma activation, more effectively than
      losartan, which decreased blood pressure to a similar extent as telmisartan.
      METHODS: Two or three branches of the left renal artery were ligated and the
      right kidney was removed to make hypertensive CKD rats. Telmisartan (5 mg/kg),
      losartan (10 mg/kg) or telmisartan plus the PPAR-gamma antagonist GW9662 was
      administered. RESULTS: Blood pressure was increased in CKD rats. Telmisartan and
      losartan decreased blood pressure to the same levels. Impaired endothelium
      dependent vasodilation, hyperplasia and decreased phospho-eNOS (Ser(1177))
      expression in CKD rat aortas were improved by telmisartan. The aortic
      infiltration by macrophages and expression of osteopontin were enhanced in CKD
      rats and suppressed by telmisartan. GW9662 partly canceled the normalization of
      vascular dysfunction. While losartan attenuated vascular changes, the extent of
      this attenuation was greater in the telmisartan-treated group. CONCLUSION:
      Telmisartan exhibited vasoprotection via PPAR-gamma agonistic properties in
      hypertensive CKD rats.

PMID- 24281042
TI  - Surveys suck: Consumer preferences when purchasing genetically engineered foods.
AB  - Many studies have attempted to gauge consumers' acceptance of genetically
      engineered or modified (GM) foods. Surveys, asking people about attitudes and
      intentions, are easy-to-collect proxies of consumer behavior. However,
      participants tend to respond as citizens of society, not discrete individuals,
      thereby inaccurately portraying their potential behavior. The Theory of Planned
      Behavior improved the accuracy of self-reported information, but its limited
      capacity to account for intention variance has been attributed to the
      hypothetical scenarios to which survey participants must respond. Valuation
      methods, asking how much consumers may be willing to pay or accept for GM foods,
      have revealed that consumers are usually willing to accept them at some price, or
      in some cases willing to pay a premium. Ultimately, it's consumers' actual--not
      intended--behavior that is of most interest to policy makers and business
      decision-makers. Real choice experiments offer the best avenue for revealing
      consumers' food choices in normal life.

PMID- 24281040
TI  - Cancer biomarkers: are we ready for the prime time?
AB  - A biomarker is a characteristic that is objectively measured and evaluated as an
      indicator of normal biologic processes, pathogenic processes, or pharmacologic
      responses to a therapeutic intervention. In cancer, a biomarker refers to a
      substance or process that is indicative of the presence of cancer in the body. A
      biomarker might be either a molecule secreted by a tumor or it can be a specific
      response of the body to the presence of cancer. Genetic, epigenetic, proteomic,
      glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis and
      epidemiology. These markers can be assayed in non-invasively collected biofluids.
      However, few cancer biomarkers are highly sensitive and specific for cancer
      detection at the present time. Consequently, biomarkers are not yet ready for
      routine use due to challenges in their clinical validation for early disease
      detection, diagnosis and monitoring to improve long-term survival of patients. 

PMID- 24281043
TI  - Chemoselective N-deacetylation under mild conditions.
AB  - A mild and efficient chemoselective N-deacetylation using the Schwartz reagent at
      room temperature in rapid time is described. The mild and neutral conditions
      enable orthogonal N-deacetylation in the presence of some of the common
      protecting groups (viz. Boc, Fmoc, Cbz, Ts). The deprotection conditions did not
      induce any epimerization at the chiral amino centre. 

PMID- 24281045
TI  - Functional isoDNA aptamers: modified thrombin binding aptamers with a 2'-5'
      linked sugar-phosphate backbone (isoTBA).
AB  - The regioisomeric 3'-deoxy-2'-5'-linked thrombin binding DNA aptamers (isoTBAs)
      were chemically synthesized and their ability to form unimolecular anti-parallel
      G-quadruplexes in the presence of K(+) ions was evaluated. These modified
      sequences retain the function of the native thrombin binding aptamer (TBA),
      exhibit better stability against exonuclease and are capable of slowing down the
      process of blood clotting. 

PMID- 24281046
TI  - Improving detection of hypertension in girls with turner syndrome using
      ambulatory blood pressure monitoring.
AB  - BACKGROUND/AIMS: Turner syndrome (TS) is associated with increased mortality due
      to cardiovascular disease and a dramatically higher rate of aortic dissection.
      The recognition and treatment of hypertension in this population is critical. We
      sought to assess the ability to detect blood pressure (BP) abnormalities
      comparing ambulatory blood pressure monitoring (ABPM) with conventional BP
      measurement methods. We hypothesized that ABPM would improve detection of
      hypertension and alter management strategies. METHODS: Twenty-three girls with TS
      underwent BP measurements using an automated oscillometric method and a manual
      mercury sphygmomanometer. Twenty-four-hour ABPM was performed (Spacelabs 90217,
      Issaquah, Wash., USA). BP values were compared to normative data based on height
      and sex for ABPM, and for age, height and sex for automated oscillometric and
      manual measurements. RESULTS: Five (22%) subjects were found to have ambulatory
      hypertension (3 of these with severe hypertension). Three subjects had
      prehypertension using ABPM measurements. Only 1 of the 5 patients with ambulatory
      hypertension was categorized as hypertensive using manual BP measurements. Twelve
      subjects (52%) had nocturnal hypertension. ABPM data led to a change in medical
      management of hypertensive patients with initiation of antihypertensive therapy.
      CONCLUSIONS: ABPM is advantageous in TS, as it improves detection of
      hypertension, identifies those with non-dipping BP patterns, and changes medical
      management of patients.

PMID- 24281047
TI  - Release from glomerular overload by the addition of low-dose thiazide in patients
      with angiotensin receptor blocker-resistant hypertension.
AB  - BACKGROUND/AIMS: This multicenter, prospective, observational study assessed the
      renoprotective effects of losartan/thiazide combination therapy in terms of
      lowering the estimated glomerular filtration rate (eGFR). METHODS: Adult patients
      with angiotensin receptor blocker (ARB)-resistant essential hypertension (n =
      104) were enrolled and switched to combination therapy with losartan (50 mg/day)
      and hydrochlorothiazide (12.5 mg/day). RESULTS: eGFR values declined
      significantly during the first 3 months, and changes in eGFR were assessed
      according to tertiles of the eGFR decrease ratio at 3 months. Only the high eGFR
      decrease (1st tertile) group showed significantly greater decreases in baseline
      eGFR and albumin-to-creatinine ratio (ACR) during the first 3 months.
      Additionally, the assessment according to tertiles of the baseline eGFR showed a
      signifcant decrease in eGFR and ACR during the first 3 months in the high
      baseline eGFR (1st tertile) group, but not in the moderate (2nd tertile) and low
      baseline eGFR (3rd tertile) groups. CONCLUSION: The present results revealed that
      losartan/thiazide combination therapy attenuated glomerular overload, indicating
      that this therapy may provide glomerular protection in patients with an elevated
      GFR without causing prolonged damage to renal function.

PMID- 24281048
TI  - Composition and expression of conserved microRNA genes in diploid cotton
      (Gossypium) species.
AB  - MicroRNAs are ubiquitous in plant genomes but vary greatly in their abundance
      within and conservation among plant lineages. To gain insight into the
      evolutionary birth/death dynamics of microRNA families, we sequenced small RNA
      and 5'-end PARE libraries generated from two closely related species of
      Gossypium. Here, we demonstrate that 33 microRNA families, with similar copy
      numbers and average evolutionary rates, are conserved in the two congeneric
      cottons. Analysis of the presence/absence of these microRNA families in other
      land plants sheds light on their depth of phylogenetic origin and lineage
      specific loss/gain. Conserved microRNA families in Gossypium exhibit a striking
      interspecific asymmetry in expression, potentially connected to relative
      proximity to neighboring transposable elements. A complex correlated expression
      pattern of microRNA target genes with their controlling microRNAs indicates that
      possible functional divergence of conserved microRNA families can also exist even
      within a single plant genus.

PMID- 24281049
TI  - The deep roots of the rings of life.
AB  - Reconstructing early evolutionary events like the origins of informational and
      operational genes, membranes, and photophosphorylation is difficult because early
      evolutionary events can be masked by subsequent gene flows. Furthermore, as
      evolution progresses through both Darwinian survival of the fittest (tree-like
      evolution) and symbiotic/endosymbiotic cooperation (ring-like evolution), trees
      alone are not adequate to represent Earth's evolutionary history. Here, we
      reconstruct and root the New Rings of Life and use it as a framework for
      interpreting early events in the evolution of life. Unlike the three-domain
      hypothesis, the rings do not fit all life into one of three immutable categories,
      but rather accommodate new gene flows as novel organisms are discovered. A draft
      of the Rooted Rings of Life is reconstructed by analyzing the phylogenetic
      distributions of indels (insertions/deletions) and genes coding for fundamental
      molecular processes. Their phylogenetic distributions are inconsistent with all
      trees. Hypergeometric distribution analyses of them strongly localize the root of
      the rings to a segment of the deepest ring (P < 10(-21) and P < 10(-194)), and
      whole-genome analyses independently confirm the topology of the rooted rings (P <
      7.1 * 10(-6)). The rings identify several large gene flows, including a flow of a
      thousand genes into the Halobacteria and the Eubacteria, the related photocyte
      flow, the flow of genes into the last common ancestor of the eocytes and the
      eukaryotes, and the informational and operational gene flows into the eukaryotes.
      The rooted rings also chronologically order steps in the evolution of extant
      taxa, that is, phototrophy evolved from Halobacteria (photophosphorylation) ->
      Heliobacteria (photosynthesis) -> Cyanobacteria (oxygenic photosynthesis).

PMID- 24281051
TI  - Spontaneous supersaturation of calcium D-gluconate during isothermal dissolution
      of calcium L-lactate in aqueous sodium D-gluconate.
AB  - Continuing dissolution of solid calcium L-lactate pentahydrate in saturated
      aqueous solutions following addition of solid sodium D-gluconate corresponding to
      a gluconate/lactate ratio around three was found to result in homogeneous
      solutions supersaturated with calcium D-gluconate by a factor of seven, from
      which calcium D-gluconate monohydrate precipitated only slowly. In contrast,
      dissolution of calcium D-gluconate monohydrate by sodium L-lactate in aqueous
      solution with the reverse lactate/gluconate ratio also around three did not
      result in similar homogeneous solutions on the route to solid calcium L-lactate
      pentahydrate. This increasing supersaturation of calcium D-gluconate during
      dissolution of calcium L-lactate in aqueous sodium D-gluconate may enhance
      calcium bioavailability. The dissolution overshooting depends on competitive
      kinetics and is also of interest in modeling biomineralization and in designing
      novel food products with increased calcium bioavailability.

PMID- 24281050
TI  - Being Aquifex aeolicus: Untangling a hyperthermophile's checkered past.
AB  - Lateral gene transfer (LGT) is an important factor contributing to the evolution
      of prokaryotic genomes. The Aquificae are a hyperthermophilic bacterial group
      whose genes show affiliations to many other lineages, including the
      hyperthermophilic Thermotogae, the Proteobacteria, and the Archaea. Previous
      phylogenomic analyses focused on Aquifex aeolicus identified Thermotogae and
      Aquificae either as successive early branches or sisters in a rooted bacterial
      phylogeny, but many phylogenies and cellular traits have suggested a stronger
      affiliation with the Epsilonproteobacteria. Different scenarios for the evolution
      of the Aquificae yield different phylogenetic predictions. Here, we outline these
      scenarios and consider the fit of the available data, including three sequenced
      Aquificae genomes, to different sets of predictions. Evidence from phylogenetic
      profiles and trees suggests that the Epsilonproteobacteria have the strongest
      affinities with the three Aquificae analyzed. However, this pattern is shown by
      only a minority of encoded proteins, and the Archaea, many lineages of
      thermophilic bacteria, and members of genus Clostridium and class
      Deltaproteobacteria also show strong connections to the Aquificae. The
      phylogenetic affiliations of different functional subsystems showed strong
      biases: Most but not all genes implicated in the core translational apparatus
      tended to group Aquificae with Thermotogae, whereas a wide range of metabolic and
      cellular processes strongly supported the link between Aquificae and
      Epsilonproteobacteria. Depending on which sets of genes are privileged, either
      Thermotogae or Epsilonproteobacteria is the most plausible adjacent lineage to
      the Aquificae. Both scenarios require massive sharing of genes to explain the
      history of this enigmatic group, whose history is further complicated by specific
      affinities of different members of Aquificae to different partner lineages.

PMID- 24281052
TI  - Superficial siderosis of the central nervous system: a post-mortem 7.0-tesla
      magnetic resonance imaging study with neuropathological correlates.
AB  - BACKGROUND: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic
      resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid
      angiopathy (CAA). The present study investigates with 7.0-tesla MRI the
      prevalence of SS and its underlying pathological substrate in a consecutive
      series of post-mortem brains of elderly patients with various neurodegenerative
      and cerebrovascular lesions. MATERIALS AND METHODS: The prevalence of SS and
      associated lesions was screened using 7.0-tesla MRI and their neuropathological
      correlates in 120 post-mortem brains of patients with various neurodegenerative
      and cerebrovascular diseases. RESULTS: Eighty-three separate zones of SS were
      detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58
      areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially
      related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was
      connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the
      15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma
      in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS
      was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains
      (p = 0.03). CONCLUSIONS: SS is associated with both haemorrhagic and ischaemic
      underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and
      two types of SS may be described. Clinicians should keep in mind that SS may be
      found in other settings than CAA.

PMID- 24281053
TI  - Too Fit To Fracture: exercise recommendations for individuals with osteoporosis
      or osteoporotic vertebral fracture.
AB  - SUMMARY: A consensus process was conducted to develop exercise recommendations
      for individuals with osteoporosis or vertebral fractures. A multicomponent
      exercise program that includes balance and resistance training is recommended.
      INTRODUCTION: The aim was to develop consensus on exercise recommendations for
      older adults: (1) with osteoporosis and (2) with osteoporotic vertebral
      fracture(s). METHODS: The Grading of Recommendations Assessment, Development, and
      Evaluation method was used to evaluate the quality of evidence and develop
      recommendations. Outcomes important for decision making were nominated by an
      expert panel and patient advocates. They included falls, fractures, bone mineral
      density (BMD), and adverse events for individuals with osteoporosis/vertebral
      fractures, and pain, quality of life, and function for those with vertebral
      fracture. Meta-analyses evaluating the effects of exercise on the outcomes were
      reviewed. Observational studies or clinical trials were reviewed when meta
      analyses were not available. Quality ratings were generated, and informed the
      recommendations. RESULTS: The outcome for which evidence is strongest is falls.
      Point estimates of the effects of exercise on falls, fractures, and BMD vary
      according to exercise type. There is not enough evidence to quantify the risks of
      exercise in those with osteoporosis or vertebral fracture. Few trials of exercise
      exist in those with vertebral fracture. The exercise recommendations for exercise
      in individuals with osteoporosis or osteoporotic vertebral fracture are
      conditional. The panel strongly recommends a multicomponent exercise program
      including resistance and balance training for individuals with osteoporosis or
      osteoporotic vertebral fracture. The panel recommends that older adults with
      osteoporosis or vertebral fracture do not engage in aerobic training to the
      exclusion of resistance or balance training. CONCLUSIONS: The consensus of our
      international panel is that exercise is recommended for older adults with
      osteoporosis or vertebral fracture, but our recommendations are conditional.

PMID- 24281056
TI  - Imaging the transcriptome.

PMID- 24281054
TI  - Association of matrix Gla protein gene functional polymorphisms with loss of bone
      mineral density and progression of aortic calcification.
AB  - Two matrix Gla protein (MGP) polymorphisms were associated with progression of
      aortic calcification and femoral neck bone loss in men. All these findings were
      also functionally corroborated in two vascular and bone in vitro systems
      indicating that MGP genetic variations can be partly responsible of higher risk
      of bone loss and vascular calcification. INTRODUCTION: MGP plays an important
      role in bone and vascular mineralization as confirmed by MGP-deficient murine
      model. We therefore aimed to find a genetic association among -138T>C, -7G>A, and
      Thr83Ala MGP single-nucleotide polymorphisms (SNPs), bone loss, and progression
      of aortic calcification in a randomly selected general population of 296
      individuals who participated in the European Vertebral Osteoporosis Study.
      METHODS: To evaluate the rate of change in bone mineral density (BMD) and the
      progression of aortic calcification, dual X-ray absorptiometry and lateral spine
      X-rays were performed at baseline and after 4 years of follow-up. Genotyping for
      the three polymorphisms was carried out using polymerase chain reaction and
      restriction fragment length analysis. In addition, functional studies of MGP-7G>A
      and Thr83Ala SNPs were performed on transiently transfected osteoblast-like UMR
      106 and vascular smooth muscle A7r5 cells. RESULTS: The proportion of men who had
      lost BMD in the femoral neck was higher among homozygous -7AA and 83Ala-Ala (p =
      0.039 and p = 0.009, respectively), and also featured a higher risk of
      progression of aortic calcifications (OR = 5.6, 95% CI = 1.2-27.8 and OR = 6.8,
      95% CI = 1.4-32.3, respectively). No effect was observed in women. The MGP-7A
      allele produced a reduction in luciferase activity compared to MGP-7G: 47% less
      in vascular cells and 34% less in bone cells (p = 0.001 and 0.012, respectively).
      In vascular cells under calcifying conditions, the MGP 83Thr allele showed a
      slightly higher, although not significant, inhibition than the MGP 83 Ala allele
      in calcium content suggesting functional differences between both variants.
      CONCLUSION: These results suggest that MGP genetic variations could predict a
      higher risk of bone loss and progression of vascular calcification in men.

PMID- 24281055
TI  - Transcriptional regulation is insufficient to explain substrate-induced flux
      changes in Bacillus subtilis.
AB  - One of the key ways in which microbes are thought to regulate their metabolism is
      by modulating the availability of enzymes through transcriptional regulation.
      However, the limited success of efforts to manipulate metabolic fluxes by
      rewiring the transcriptional network has cast doubt on the idea that transcript
      abundance controls metabolic fluxes. In this study, we investigate control of
      metabolic flux in the model bacterium Bacillus subtilis by quantifying fluxes,
      transcripts, and metabolites in eight metabolic states enforced by different
      environmental conditions. We find that most enzymes whose flux switches between
      on and off states, such as those involved in substrate uptake, exhibit large
      corresponding transcriptional changes. However, for the majority of enzymes in
      central metabolism, enzyme concentrations were insufficient to explain the
      observed fluxes--only for a number of reactions in the tricarboxylic acid cycle
      were enzyme changes approximately proportional to flux changes. Surprisingly,
      substrate changes revealed by metabolomics were also insufficient to explain
      observed fluxes, leaving a large role for allosteric regulation and enzyme
      modification in the control of metabolic fluxes.

PMID- 24281057
TI  - Haematological cancer: Richter's transformation in CLL-a distinct lymphoma.
AB  - A landmark study has delineated and identified the genetic pathways that drive
      the natural course of chronic lymphocytic leukaemia (CLL) B cells into Richter's
      transformation. CLL-related Richter's transformation is a distinct lymphoma, and
      poses various questions about B-cell ontogeny and relevance of B cell receptor
      signalling inhibitors.

PMID- 24281058
TI  - Breast cancer: targeted intraoperative radiotherapy - one pit stop for breast
      cancer treatment.

PMID- 24281059
TI  - Biomarker enrichment strategies: matching trial design to biomarker credentials.
AB  - The use of biomarkers to identify patients who can benefit from treatment with a
      specific anticancer agent has the potential to both improve patient care and
      accelerate drug development. The development of targeted agents and their
      accompanying biomarkers frequently occurs contemporaneously, and confidence in a
      putative biomarker's performance might, therefore, be insufficient to restrict
      the definitive testing of a new agent to the subgroup of biomarker-positive
      patients. This Review considers which clinical trial designs and analysis
      strategies are appropriate for use in phase III, biomarker-driven, randomized
      clinical trials, on the basis of pre-existing evidence that the biomarker can
      successfully identify patients who will respond to the treatment in question. The
      types of interim monitoring that are appropriate for these trials are also
      discussed. In addition, enrichment strategies based on the use of prognostic
      biomarkers to separate a population into subgroups with better and worse
      outcomes, regardless of treatment, are described. Finally, the possibility of
      formally using a biomarker during phase II drug development, to select what type
      of biomarker-driven strategy should be used in the phase III trial, is discussed.

PMID- 24281060
TI  - Targeted therapies: early vessel normalization improves glioblastoma outcomes.

PMID- 24281063
TI  - Lung cancer: cetuximab, you're fired.

PMID- 24281062
TI  - End-of-life care--what do cancer patients want?
AB  - Patients with cancer frequently suffer from debilitating physical symptoms and
      psychological distress, particularly at the end of life. Interventions to help
      alleviate these problems are often complex and multifactorial. Palliative care
      services and therapeutic interventions have developed in a variable manner, often
      with limited evaluation of clinical effectiveness and affordability, resulting in
      a relatively weak evidence base. The health care provided to patients with
      advanced-stage cancer does not always correlate with what is known about their
      preferences for care. In this Review, we discuss the preferences of patients with
      cancer regarding their end of life care, including the importance of early
      provision of palliative care, and the central role of advance care planning in
      meeting patients' preferences. It has been shown that many patients with cancer
      wish to die at home. We discuss the factors that contribute to the place of
      death, including environmental factors, disease-specific issues, and the
      availability of resources. There has been a recent upward trend in the number of
      patients with cancer who die in their preferred place of care, and important
      contributors--such as community palliative care, advance care planning, and
      improvements in palliative care services as a result of robust research studies-
      are considered.

PMID- 24281061
TI  - Future directions in the prevention of prostate cancer.
AB  - The high global incidence of prostate cancer has led to a focus on
      chemoprevention strategies to reduce the public health impact of the disease.
      Early studies indicating that selenium and vitamin E might protect against
      prostate cancer encouraged large-scale studies that produced mixed clinical
      results. Next-generation prostate cancer prevention trials validated the impact
      of 5alpha-reductase inhibitors in hormone-responsive prostate cancer, and these
      results were confirmed in follow-up studies. Other interventions on the horizon,
      involving both dietary and pharmacological agents, hold some promise but require
      further investigation to validate their efficacy. In this Review, we discuss the
      clinical and preclinical evidence for dietary and pharmacological prevention of
      prostate cancer and give an overview of future opportunities for chemoprevention.

PMID- 24281064
TI  - Prosodic marking, pitch and intensity in spontaneous lexical self-repair in
      dutch.
AB  - This paper presents results of a phonetic analysis of instances of lexical self
      repair drawn from a corpus of spontaneous Dutch speech. The analysis addresses
      questions concerning the phonetic details of prosodic marking in self-repair and
      its conditioning factors. In particular, it examines the relevance of semantic,
      temporal and frequency-related factors in modelling f0 and intensity measures and
      auditory judgements of whether repairs are prosodically marked. It addresses the
      extent to which observations made in studies using experimentally-elicited speech
      can be expected to generalise to repairs drawn from uncontrolled spontaneous
      speech. The results suggest that prosodic marking is rare in spontaneous lexical
      self-repair, and that semantic, temporal and frequency factors play a limited
      role only in conditioning speakers' choices for or against prosodic marking,
      although several weak tendencies can be observed.

PMID- 24281065
TI  - Segmental and prosodic effects on intervocalic voiced stop reduction in connected
      speech.
AB  - De scriptions of lenition have often assumed that connected speech reductions are
      the phonetic precursors of phonological lenition processes. In this article,
      production of intervocalic voiced stops during reading in American English is
      examined to determine whether connected speech reduction processes mirror the
      stages of lenition that have been posited in the phonological literature. The
      first result shows that American English speakers never lenite to fricatives or
      debuccalize to [h] or glottal stop, but rather produce approximants whenever
      reduction occurs. Second, stress plays an essential role: 51% of stops are
      produced as approximants when stress is on the preceding syllable (e.g. 'yoga'),
      but only 7% of stops weaken when stress is on the following syllable (e.g.
      'lagoon'). Approximant productions are longer and higher in intensity than stop
      productions when stress precedes the target consonant, but when stress follows
      the target consonant, the stop cues are enhanced. These acoustic findings suggest
      that English speakers prioritize the realization of acoustic cues to stress,
      including the robust production of stop consonants, over pressures to reduce or
      weaken consonants in intervocalic position.

PMID- 24281066
TI  - Sonorant onset pitch as a perceptual cue of lexical tones in Mandarin.
AB  - Lexical tone identification requires a number of secondary cues, when main tonal
      contours are unavailable. In this article, we examine Mandarin native speakers'
      ability to identify lexical tones by extracting tonal information from sonorant
      onset pitch (onset contours) on syllable-initial nasals ranging from 50 to 70 ms
      in duration. In experiments I and II we test speakers' ability to identify
      lexical tones in a second syllable with and without onset contours in isolation
      (experiment I) and in a sentential context (experiment II). The results indicate
      that speakers can identify lexical tones with short distinctive onset contour
      patterns,they also indicate that misperception of tones 213 and 24 are common.
      Furthermore, in experiment III, we test whether onset contours in a following
      syllable can be utilized by listeners in tone identification. We find that onset
      contours in the following syllable also contribute to the identification of the
      target lexical tones. The conclusions are twofold: (1) Mandarin lexical tones can
      be identified with onset contours; (2) tonal domain must be extended to include
      not just typical cues of tones but also coarticulated tonal patterns.

PMID- 24281068
TI  - Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor
      Oxygenation.
AB  - Thioredoxin is a small redox-regulating protein, which plays crucial roles in
      maintaining cellular redox homeostasis and cell survival and is highly expressed
      in many cancers. The tumor environment is usually under either oxidative or
      hypoxic stress and both stresses are known up-regulators of thioredoxin
      expression. These environments exist in tumors because their abnormal vascular
      networks result in an unstable oxygen delivery. Therefore, the oxygenation
      patterns in human tumors are complex, leading to hypoxia/re-oxygenation cycling.
      During carcinogenesis, tumor cells often become more resistant to hypoxia or
      oxidative stress-induced cell death and most studies on tumor oxygenation have
      focused on these two tumor environments. However, recent investigations suggest
      that the hypoxic cycling occurring within tumors plays a larger role in the
      contribution to tumor cell survival than either oxidative stress or hypoxia
      alone. Thioredoxin is known to have important roles in both these cellular
      responses and several studies implicate thioredoxin as a contributor to cancer
      progression. However, only a few studies exist that investigate the regulation of
      thioredoxin in the hypoxic and cycling hypoxic response in cancers. This review
      focuses on the role of thioredoxin in the various states of tumor oxygenation. 

PMID- 24281069
TI  - Identification of Insulin-Like Growth Factor-I Receptor (IGF-IR) Gene Promoter
      Binding Proteins in Estrogen Receptor (ER)-Positive and ER-Depleted Breast Cancer
      Cells.
AB  - The insulin-like growth factor I receptor (IGF-IR) has been implicated in the
      etiology of breast cancer. Overexpression of the IGF-IR gene is a typical feature
      of most primary breast cancers, whereas low IGF-IR levels are seen at advanced
      stages. Hence, evaluation of IGF-IR levels might be important for assessing
      prognosis. In the present study, we employed a proteomic approach based on DNA
      affinity chromatography followed either by mass spectroscopy (MS) or Western blot
      analysis to identify transcription factors that may associate with the IGF-IR
      promoter in estrogen receptor (ER)-positive and ER-depleted breast cancer cells.
      A biotinylated IGF-IR promoter fragment was bound to streptavidin magnetic beads
      and incubated with nuclear extracts of breast cancer cells. IGF-IR promoter
      binding proteins were eluted with high salt and analyzed by MS and Western blots.
      Among the proteins that were found to bind to the IGF-IR promoter we identified
      zinc finger transcription factors Sp1 and KLF6, ER-, p53, c-jun, and poly (ADP
      ribosylation) polymerase. Furthermore, chromatin immune-precipitation (ChIP)
      analysis confirmed the direct in vivo binding of some of these transcription
      factors to IGF-IR promoter DNA. The functional relevance of binding data was
      assessed by cotransfection experiments with specific expression vectors along
      with an IGF-IR promoter reporter. In summary, we identified nuclear proteins that
      are potentially responsible for the differential expression of the IGF-IR gene in
      ER-positive and ER-depleted breast cancer cells. 

PMID- 24281070
TI  - Automated dermoscopy image analysis of pigmented skin lesions.
AB  - Dermoscopy (dermatoscopy, epiluminescence microscopy) is a non-invasive
      diagnostic technique for the in vivo observation of pigmented skin lesions
      (PSLs), allowing a better visualization of surface and subsurface structures
      (from the epidermis to the papillary dermis). This diagnostic tool permits the
      recognition of morphologic structures not visible by the naked eye, thus opening
      a new dimension in the analysis of the clinical morphologic features of PSLs. In
      order to reduce the learning-curve of non-expert clinicians and to mitigate
      problems inherent in the reliability and reproducibility of the diagnostic
      criteria used in pattern analysis, several indicative methods based on diagnostic
      algorithms have been introduced in the last few years. Recently, numerous systems
      designed to provide computer-aided analysis of digital images obtained by
      dermoscopy have been reported in the literature. The goal of this article is to
      review these systems, focusing on the most recent approaches based on content
      based image retrieval systems (CBIR). 

PMID- 24281072
TI  - Surgery triggers outgrowth of latent distant disease in breast cancer: an
      inconvenient truth?
AB  - We review our work over the past 14 years that began when we were first
      confronted with bimodal relapse patterns in two breast cancer databases from
      different countries. These data were unexplainable with the accepted continuous
      tumor growth paradigm. To explain these data, we proposed that metastatic breast
      cancer growth commonly includes periods of temporary dormancy at both the single
      cell phase and the avascular micrometastasis phase. We also suggested that
      surgery to remove the primary tumor often terminates dormancy resulting in
      accelerated relapses. These iatrogenic events are apparently very common in that
      over half of all metastatic relapses progress in that manner. Assuming this is
      true, there should be ample and clear evidence in clinical data. We review here
      the breast cancer paradigm from a variety of historical, clinical, and scientific
      perspectives and consider how dormancy and surgery-driven escape from dormancy
      would be observed and what this would mean. Dormancy can be identified in these
      diverse data but most conspicuous is the sudden synchronized escape from dormancy
      following primary surgery. On the basis of our findings, we suggest a new
      paradigm for early stage breast cancer. We also suggest a new treatment that is
      meant to stabilize and preserve dormancy rather than attempt to kill all cancer
      cells as is the present strategy. 

PMID- 24281071
TI  - Oxidative and nitrosative stress in the metastatic microenvironment.
AB  - Metastases that are resistant to conventional therapies are the main cause of
      most cancer-related deaths in humans. Tumor cell heterogeneity, which associates
      with genomic and phenotypic instability, represents a major problem for cancer
      therapy. Additional factors, such as the attack of immune cells or organ-specific
      microenvironments, also influence metastatic cell behavior and the response to
      therapy. Interaction of cancer and endothelial cells in capillary beds, involving
      mechanical contact and transient adhesion, is a critical step in the initiation
      of metastasis. This interaction initiates a cascade of activation pathways that
      involves cytokines, growth factors, bioactive lipids and reactive oxygen and
      nitrogen species (ROS and RNS) produced by either the cancer cell or the
      endothelium. Vascular endothelium-derived NO and H2O2 are cytotoxic for the
      cancer cells, but also help to identify some critical molecular targets that
      appear essential for survival of invasive metastatic cell subsets. Surviving
      cancer cells that extravasate and start colonization of an organ or tissue can
      still be attacked by macrophages and be influenced by specific intraorgan
      microenvironment conditions. At all steps; from the primary tumor until
      colonization of a distant organ; metastatic cells undergo a dynamic process of
      constant adaptations that may lead to the survival of highly resistant malignant
      cell subsets. In this sequence of molecular events both ROS and RNS play key
      roles. 

PMID- 24281074
TI  - Cerebral metastases from malignant melanoma: current treatment strategies,
      advances in novel therapeutics and future directions.
AB  - Of all primary cancers in humans, melanoma has the highest propensity to
      metastasize to the brain. The prognosis of patients with this disease is
      extremely poor. Due to its radioresistance and poor response to existing
      chemotherapeutic regimes, no treatment options other than surgical extirpation,
      when feasible, have been shown to be effective. An understanding of the
      underlying tumor biology therefore remains the cornerstone of offering new hope
      in the treatment. In this review, we comment on the current treatment strategies
      for melanoma brain metastases and summarize some recent experimental findings
      from our laboratory with potential for the development of target specific
      antitumor therapies. 

PMID- 24281073
TI  - The "two-faced" effects of reactive oxygen species and the lipid peroxidation
      product 4-hydroxynonenal in the hallmarks of cancer.
AB  - Reacytive Oxygen Species (ROS) have long been considered to be involved in the
      initiation, progression and metastasis of cancer. However, accumulating evidence
      points to the benefical role of ROS. Moreover, ROS production, leading to
      apoptosis, is the mechanism by which many chemotherapeutic agents can act. Beside
      direct actions, ROS elicit lipid peroxidation, leading to the production of 4
      hydroxynoneal (HNE). Interestingly, HNE also seems to have a dual behaviour with
      respect to cancer. In this review we present recent literature data which outline
      the "two-faced" character of oxidative stress and lipid peroxidation in
      carcinogenesis and in the hallmarks of cancer. 

PMID- 24281075
TI  - The role of oxidative stress in carcinogenesis induced by metals and xenobiotics.
AB  - In addition to a wide range of adverse effects on human health, toxic metals such
      as cadmium, arsenic and nickel can also promote carcinogenesis. The toxicological
      properties of these metals are partly related to generation of reactive oxygen
      species (ROS) that can induce DNA damage and trigger redox-dependent
      transcription factors. The precise mechanisms that induce oxidative stress are
      not fully understood. Further, it is not yet known whether chronic exposures to
      low doses of arsenic, cadmium or other metals are sufficient to induce mutations
      in vivo, leading to DNA repair responses and/or tumorigenesis. Oxidative stress
      can also be induced by environmental xenobiotics, when certain metabolites are
      generated that lead to the continuous release of superoxide, as long as the
      capacity to reduce the resulting dions (quinones) into hydroquinones is
      maintained. However, the specific significance of superoxide-dependent pathways
      to carcinogenesis is often difficult to address, because formation of DNA adducts
      by mutagenic metabolites can occur in parallel. Here, we will review both
      mechanisms and toxicological consequences of oxidative stress triggered by metals
      and dietary or environmental pollutants in general. Besides causing DNA damage,
      ROS may further induce multiple intracellular signaling pathways, notably NF-kB,
      JNK/SAPK/p38, as well as Erk/MAPK. These signaling routes can lead to
      transcriptional induction of target genes that could promote proliferation or
      confer apoptosis resistance to exposed cells. The significance of these
      additional modes depends on tissue, cell-type and is often masked by alternate
      oncogenic mechanisms being activated in parallel. 

PMID- 24281076
TI  - Current research and development of chemotherapeutic agents for melanoma.
AB  - Cutaneous malignant melanoma is the most lethal form of skin cancer and an
      increasingly common disease worldwide. It remains one of the most treatment
      refractory malignancies. The current treatment options for patients with
      metastatic melanoma are limited and in most cases non-curative. This review
      focuses on conventional chemotherapeutic drugs for melanoma treatment, by a
      single or combinational agent approach, but also summarizes some potential novel
      phytoagents discovered from dietary vegetables or traditional herbal medicines as
      alternative options or future medicine for melanoma prevention. We explore the
      mode of actions of these natural phytoagents against metastatic melanoma. 

PMID- 24281077
TI  - Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood
      Lymphocytes from a Brain Tumor Case-Control Study.
AB  - Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence
      remains through life. An association between HCMV infection and malignant gliomas
      has been reported, suggesting that HCMV may play a role in glioma pathogenesis
      and could facilitate an accrual of genotoxic damage in the presence of g
      radiation; an established risk factor for gliomas. We tested the hypothesis that
      HCMV infection modifies the sensitivity of cells to gamma-radiation-induced
      genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma
      patients and 100 controls to measure the level of chromosome damage and cell
      death. We evaluated baseline, HCMV-, gamma-radiation and HCMV + gamma-radiation
      induced genetic instability with the comprehensive Cytokinesis-Blocked
      Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant
      increase in aberration frequency among cases and controls. PBLs infected with
      HCMV prior to challenge with gamma-radiation led to a significant increase in
      aberrations as compared to baseline, gamma-radiation and HCMV alone. With regards
      to apoptosis, glioma cases showed a lower percentage of induction following in
      vitro exposure to gamma-radiation and HCMV infection as compared to controls.
      This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to
      gamma-radiation-induced genetic damage possibly through an increase in chromosome
      damage and decrease in apoptosis. 

PMID- 24281078
TI  - Nrf2 and NF-kappaB and Their Concerted Modulation in Cancer Pathogenesis and
      Progression.
AB  - Reactive oxygen species, produced by oxidative stress, are implicated in the
      initiation, promotion, and malignant conversion of carcinogenesis through
      activation/suppression of redox-sensitive transcription factors. NF-E2-related
      factor 2 (Nrf2) encodes for antioxidant and general cytoprotection genes, while
      NF-kappaB regulates the expression of pro-inflammatory genes. A variety of anti
      inflammatory or anti-carcinogenic phyto-chemicals suppress NF-kappaB signalling
      and activate the Nrf2-ARE pathway. In this review we consider the role of Nrf2
      and NF-kappaB in cancer pathogenesis and progression, focusing on their concerted
      modulation and potential cross-talk. 

PMID- 24281079
TI  - Possible DNA viral factors of human breast cancer.
AB  - Viruses are considered to be one of the high-risk factors closely related to
      human breast cancer. However, different studies of viruses in breast cancer
      present conflicting results and some of these works remain in dispute. DNA
      viruses, such as specific types of human papillomaviruses (HPV), Epstein-Barr
      virus (EBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and human
      herpes virus type 8 (HHV-8), have emerged as causal factors of some human
      cancers. These respective exogenous viruses and the possibility of multiple viral
      factors are discussed in this review. 

PMID- 24281080
TI  - Responsiveness of urinary and plasma alkylresorcinol metabolites to rye intake in
      finnish women.
AB  - Alkylresorcinols [ARs] have been proposed for use as biomarkers of whole-grain
      intake. The aim here was to examine the responsiveness of AR metabolites to rye
      intake. Sixty women were divided into three groups according to their rye
      consumption. We observed significant differences between groups in plasma 3-[3,5
      dihydroxyphenyl]-1-propanoic acid [DHPPA] and in urinary DHPPA and 3,5
      dihydroxybenzoic acid [DHBA]. In addition, these AR metabolites increased
      proportionally to rye fiber intake. We conclude that these ARs metabolites are
      accurate and useful biomarkers of rye fiber intake. Further studies are needed to
      confirm our results in larger and different populations. 

PMID- 24281081
TI  - Biomarkers for early detection of malignant mesothelioma: diagnostic and
      therapeutic application.
AB  - Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal
      cavities linked to asbestos exposure. Improved detection methods for diagnosing
      this type of neoplastic disease are essential for an early and reliable diagnosis
      and treatment. Thus, focus has been placed on finding tumour markers for the non
      invasive detection of MM. Recently, some blood biomarkers have been described as
      potential indicators of early and advanced MM cancers. The identification of
      tumour biomarkers alone or in combination could greatly facilitate the
      surveillance procedure for cohorts of subjects exposed to asbestos, a common
      phenomenon in several areas of western countries. 

PMID- 24281082
TI  - Management of melanoma families.
AB  - In this review we have aimed to focus on the clinical management of familial
      melanoma patients and their relatives. Along this line three major topics will be
      discussed: (1) management/screening of familial melanoma families: what is
      advised and what is the evidence thereof; (2) variability of families worldwide
      with regard to clinical phenotype, including cancer spectrum and likelihood of
      finding germline mutations and (3) background information for clinicians on the
      molecular biology of familial melanoma and recent developments in this field. 

PMID- 24281084
TI  - The NK-1 Receptor Antagonist L-732,138 Induces Apoptosis and Counteracts
      Substance P-Related Mitogenesis in Human Melanoma Cell Lines.
AB  - It has been recently demonstrated that substance P (SP) and neurokinin-1 (NK-1)
      receptor antagonists induce cell proliferation and cell inhibition in human
      melanoma cells, respectively. However, the antitumor action of the NK-1 receptor
      antagonist L-732,138 on such cells is unknown. The aim of this study was to
      demonstrate an antitumor action of L-732,138 against three human melanoma cell
      lines (COLO 858, MEL HO, COLO 679). We found that L-732,138 elicits cell growth
      inhibition in a concentration dependent manner in the melanoma cells studied.
      Moreover, L-732,138 blocks SP mitogen stimulation. The specific antitumor action
      of L-732,138 occurred through the NK-1 receptor and melanoma cell death was by
      apoptosis. These findings indicate that the NK-1 receptor antagonist L-732,138
      could be a new antitumor agent in the treatment of human melanoma. 

PMID- 24281086
TI  - Acral lentiginous melanoma in situ: a diagnostic and management challenge.
AB  - Early stage recognition of acral lentiginous melanoma (ALM) is important for a
      better prognosis, but in-depth understanding and proper management of ALM in situ
      is complicated, because there are only a few reports, probably due to its rarity
      and diagnostic difficulty. We have reviewed our experience with seven patients
      who were diagnosed as having ALM in situ and discuss how to accurately diagnose
      and properly manage these rare lesions. Clinically the lesions showed black to
      brown discoloration of the nail with Hutchinson's sign and hyperpigmented macules
      on the heel with color variegation. All the lesions showed a diffuse lentiginous
      pattern of melanocytic proliferation with variable level of atypism along the
      dermoepidermal junction. Dermoscopic findings were available in three and
      revealed parallel ridge patterns. Confrontation of clinical and histopathologic
      findings was observed in three, and the lesions were not recognized or diagnosed
      as ALM in situ in the first place. Excision of the primary lesion with variable
      operative margin was done as an initial treatment. Recurrence was observed in
      three patients and one developed invasive ALM and lymph node metastasis.
      Integration of all available information concerning the clinical presentation,
      histopathology, and dermoscopic findings is very important and can lead to the
      best classification for correct diagnosis. Lack of knowledge upon clinical course
      and optimal margin to control ALM in situ provokes the need for further studies
      with longer follow up and larger number of cases. 

PMID- 24281083
TI  - Role of uncoupling proteins in cancer.
AB  - Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins
      whose function is to allow the re-entry of protons to the mitochondrial matrix,
      by dissipating the proton gradient and, subsequently, decreasing membrane
      potential and production of reactive oxygen species (ROS). Due to their pivotal
      role in the intersection between energy efficiency and oxidative stress, UCPs are
      being investigated for a potential role in cancer. In this review we compile the
      latest evidence showing a link between uncoupling and the carcinogenic process,
      paying special attention to their involvement in cancer initiation, progression
      and drug chemoresistance. 

PMID- 24281085
TI  - Midkine: a novel prognostic biomarker for cancer.
AB  - Since diagnosis at an early stage still remains a key issue for modern oncology
      and is crucial for successful cancer therapy, development of sensitive, specific,
      and non-invasive tumor markers, especially, in serum, is urgently needed. Midkine
      (MK), a plasma secreted protein, was initially identified in embryonal carcinoma
      cells at early stages of retinoic acid-induced differentiation. Multiple studies
      have reported that MK plays important roles in tumor progression, and is highly
      expressed in various malignant tumors. Because increased serum MK concentrations
      also have been reported in patients with various tumors, serum MK may have the
      potential to become a very useful tumor marker. Here, we review and discuss the
      possibility and usefulness of MK as a novel tumor marker. 

PMID- 24281087
TI  - MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell
      Carcinoma (OSCC).
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation,
      proliferation, development, cell cycle, and apoptosis. Expression profiling of
      miRNAs has been performed and the data show that some miRNAs are upregulated or
      downregulated in cancer. Several studies suggest that the expression profiles of
      miRNAs are associated with clinical outcomes. However, the set of miRNAs with
      altered expressing differs depending on the type of cancer, suggesting that it is
      important to understand which miRNAs are related to which cancers. Therefore,
      this review aimed to discuss potentially crucial miRNAs in head and neck squamous
      cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC). 

PMID- 24281088
TI  - Oxidative stress induced mechanisms in the progression of periodontal diseases
      and cancer: a common approach to redox homeostasis?
AB  - There is documented evidence of significant associations between cancer of the
      lung, kidney, pancreas, hematological and oral cancers and periodontal diseases
      of the supporting structures of the teeth. Enhanced lipid peroxidation, raised
      levels of TBARS and the oxidative stress marker malondealdehyde have been
      detected in breast cancer with reduced antioxidant capacity, also characteristic
      of periodontal diseases. Antioxidants could overcome this deficit and attenuate
      disease progression by down regulating glutathione detoxification/redox buffering
      system and inhibiting key transcription factors. Periodontal disease may be a
      critical marker of a susceptible immune system, or initiate cancer risk with a
      pro-oxidant inflammatory profile. 

PMID- 24281090
TI  - A novel method for sentinel lymph node biopsy by indocyanine green fluorescence
      technique in breast cancer.
AB  - We investigated the feasibility of sentinel lymph node (SLN) biopsy using
      indocyanine green (ICG) technique in 411 patients with early breast cancer at
      three institutes. ICG, a fluorescence source, and blue dye were injected into the
      subareolar area to enable real-time image-guided surgery and identification of
      SLN fluorescence after meticulous dissection. The subcutaneous lymphatic channels
      were precisely detected in all cases. SLN identification rate was 99% (408/411)
      with a mean of 2.3 nodes identified per patient. Thirty-nine cases (9.5%) had
      SLNs involved and all of them were ICG positive. Thus, the ICG technique has a
      high SLN identification rate comparable with that of the radioisotope method. 

PMID- 24281089
TI  - Role of inflammation and oxidative stress mediators in gliomas.
AB  - Gliomas are the most common primary brain tumors of the central nervous system.
      Despite relevant progress in conventional treatments, the prognosis of such
      tumors remains almost invariably dismal. The genesis of gliomas is a complex,
      multistep process that includes cellular neoplastic transformation, resistance to
      apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition
      of invasive properties. Among a number of different biomolecular events, the
      existence of molecular connections between inflammation and oxidative stress
      pathways and the development of this cancer has been demonstrated. In particular,
      the tumor microenvironment, which is largely orchestrated by inflammatory
      molecules, is an indispensable participant in the neoplastic process, promoting
      proliferation, survival and migration of such tumors. Proinflammatory cytokines,
      such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as
      well as chemokines and prostaglandins, are synthesized by resident brain cells
      and lymphocytes invading the affected brain tissue. Key mediators of cancer
      progression include nuclear factor-kappaB, reactive oxygen and nitrogen species,
      and specific microRNAs. The collective activity of these mediators is largely
      responsible for a pro-tumorigenic response through changes in cell proliferation,
      cell death, cellular senescence, DNA mutation rates, DNA methylation and
      angiogenesis. We provide a general overview of the connection between specific
      inflammation and oxidative stress pathway molecules and gliomas. The elucidation
      of specific effects and interactions of these factors may provide the opportunity
      for the identification of new target molecules leading to improved diagnosis and
      treatment. 

PMID- 24281092
TI  - Do all patients require radiotherapy after breast-conserving surgery?
AB  - Radiotherapy following breast conservation is routine in the treatment of breast
      cancer. This creates a large demand for radiotherapy services with implicit cost
      effects and potential morbidity to patients. Radiotherapy is administered to
      decrease local recurrence, but is radiotherapy required for all breast cancers? A
      literature search using the Medline and Ovid databases was conducted between 1965
      and 2010 using the terms 'role of radiotherapy', 'early breast cancer', and
      omission of radiotherapy'. Papers with clinical trials published in English in
      adult humans were included. Fourteen randomized controlled trials were included.
      Local recurrence rates range from 0.8-35% in patients in whom radiotherapy was
      omitted. Low risk characteristics include older age, small tumor size, no
      lymphovascular invasion and low to moderate grade. At present, there is no
      clearly defined low risk group of patients in whom radiotherapy can be omitted. 

PMID- 24281091
TI  - Biomarkers of the metabolic syndrome and breast cancer prognosis.
AB  - In spite of its public health importance, our understanding of the mechanisms of
      breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS)
      is a constellation of biochemical abnormalities including visceral adiposity,
      hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The
      components of the MS have all been related to late-stage disease and even to a
      poor prognosis of breast cancer through multiple interacting mechanisms. In this
      review, we aim to present a summary of recent advances in the understanding of
      the contribution of the MS to breast cancer with the emphasis on the role of
      biomarkers of the MS in the prognosis of breast cancer. 

PMID- 24281093
TI  - Viruses and breast cancer.
AB  - Viruses are the accepted cause of many important cancers including cancers of the
      cervix and anogenital area, the liver, some lymphomas, head and neck cancers and
      indirectly human immunodeficiency virus associated cancers. For over 50 years,
      there have been serious attempts to identify viruses which may have a role in
      breast cancer. Despite these efforts, the establishment of conclusive evidence
      for such a role has been elusive. However, the development of extremely
      sophisticated new experimental techniques has allowed the recent development of
      evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor
      virus and bovine leukemia virus may each have a role in the causation of human
      breast cancers. This is potentially good news as effective vaccines are already
      available to prevent infections from carcinogenic strains of human papilloma
      virus, which causes cancer of the uterine cervix. 

PMID- 24281094
TI  - Cytokines and growth factors expressed by human cutaneous melanoma.
AB  - Cytokines and growth factors have biologic effects that could stimulate tumor
      growth, invasion and angiogenesis. The incidence of 24 factors was investigated
      in 25 cultured human melanoma cell lines and in 62 fixed tissues at different
      stages of the disease. Over 80% of the human melanoma cell lines expressed TGF
      beta, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-beta, IGF-1 and
      IL-15 were determined in primary lesions compared to distant metastases by
      immunohistochemistry. Illustrating the complexity of the milieu of the tumor
      microenvironment, some of these factors may have to be considered in targeted
      therapy. 

PMID- 24281095
TI  - An Overview of Biomarkers and Molecular Signatures in HCC.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality
      worldwide. Although most HCCs seem to originate from the accumulation of genetic
      abnormalities induced by various risk factors, underlying mechanisms of
      hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also
      poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level
      is a useful marker for the detection and monitoring of HCC, AFP levels may remain
      normal in the patients even with advanced HCC. To identify useful biomarkers for
      HCC, many studies have been conducted on molecular events such as genetic and
      epigenetic alterations, and gene expression. This review summarizes recent
      studies of potential molecular markers for diagnosis and monitoring metastasis or
      recurrence of HCC. 

PMID- 24281096
TI  - Surgery of primary melanomas.
AB  - Surgery remains the mainstay of melanoma therapy, regardless of the tumor site.
      Only the early diagnosis combined with proper surgical therapy currently gives
      patients affected by this malignancy the chance for a full cure. The main goal of
      surgical therapy is to provide the local control of the disease and to secure
      long-term survival of the patient without reasonable functional and esthetic
      impairment. The recommended method of biopsy-excisional biopsy, as an initial
      diagnostic and, to some extent, therapeutic procedure-is performed under local
      anesthesia as an elliptical incision with visual clear margins of 1-3 mm and with
      some mm of subcutaneous tissue. The extent of radical excision of the primary
      tumor (or scar after excisional biopsy) is based on the histopathologic
      characteristics of the primary tumor and usually consists of 1-2 cm margins with
      primary closure. The philosophy behind conducted randomized clinical trials has
      been to find the most conservative surgical approach that is able to guarantee
      the same results as more demolitive treatment. This has been the background of
      the trials designed to define the correct margins of excision around a primary
      cutaneous melanoma. Much less definition can be dedicated to the surgical
      management of patients with non-cutaneous melanomas. 

PMID- 24281097
TI  - Platelet proteome and tumor dormancy: can platelets content serve as predictive
      biomarkers for exit of tumors from dormancy?
AB  - Although tumor dormancy is highly prevalent, the underling mechanisms are still
      mostly unknown. It is unclear which lesions will progress and become a
      disseminated cancer, and which will remain dormant and asymptomatic. Yet, an
      improved ability to predict progression would open the possibility of timely
      treatment and improvement in outcomes. We have recently described the ability of
      platelets to selectively uptake angiogenesis regulators very early in tumor
      growth, and proposed their use as an early marker of malignancy. In this review
      we will summarize current knowledge about these processes and will discuss the
      possibility of using platelet content to predict presence of occult tumors. 

PMID- 24281098
TI  - Role of oxidative stress in stem, cancer, and cancer stem cells.
AB  - The term ''oxidative stress" refers to a cell's state characterized by excessive
      production of reactive oxygen species (ROS) and oxidative stress is one of the
      most important regulatory mechanisms for stem, cancer, and cancer stem cells. The
      concept of cancer stem cells arose from observations of similarities between the
      self-renewal mechanism of stem cells and that of cancer stem cells, but compared
      to normal stem cells, they are believed to have no control over the cell number.
      ROS have been implicated in diverse processes in various cancers, and generally
      the increase of ROS in cancer cells is known to play an important role in the
      initiation and progression of cancer. Additionally, ROS have been considered as
      the most significant mutagens in stem cells; when elevated, blocking self-renewal
      and at the same time, serving as a signal stimulating stem cell differentiation.
      Several signaling pathways enhanced by oxidative stress are suggested to have
      important roles in tumorigenesis of cancer or cancer stem cells and the self
      renewal ability of stem or cancer stem cells. It is now well established that
      mitochondria play a prominent role in apoptosis and increasing evidence supports
      that apoptosis and autophagy are physiological phenomena closely linked with
      oxidative stress. This review elucidates the effect and the mechanism of the
      oxidative stress on the regulation of stem, cancer, and cancer stem cells and
      focuses on the cell signaling cascades stimulated by oxidative stress and their
      mechanism in cancer stem cell formation, as very little is known about the redox
      status in cancer stem cells. Moreover, we explain the link between ROS and both
      of apoptosis and autophagy and the impact on cancer development and treatment.
      Better understanding of this intricate link may shed light on mechanisms that
      lead to better modes of cancer treatment. 

PMID- 24281099
TI  - The evolution of biomarkers in thyroid cancer-from mass screening to a
      personalized biosignature.
AB  - Thyroid cancer is the most common malignancy of the endocrine system. The
      diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a
      common event occurring in over 50% of the patient population over the age of 50.
      Yet, only 5% of these patients will be diagnosed with cancer. Fine needle
      aspiration biopsy is the gold standard for diagnosing thyroid nodules. However,
      10-15% of these biopsies are inconclusive, ultimately requiring a diagnostic
      thyroid lobectomy. Consequently, research in thyroid biomarkers has become an
      area of active interest. In the 40 years since calcitonin was first described as
      the biomarker for medullary thyroid cancer, new biomarkers in thyroid cancer have
      been discovered. Advances in genomic and proteomic technologies have defined many
      of these novel thyroid biomarkers. The purpose of this article is to provide a
      comprehensive literature review of how these biomarkers have evolved from simple
      screening tests into a complex array of multiple markers to help predict the
      malignant potential and genetic signature of thyroid neoplasms. 

PMID- 24281101
TI  - Systemic therapy of non-resectable metastatic melanoma.
AB  - In advanced metastatic melanoma (non-resectable stage III/IV), the prognosis
      still remains poor, with median survival times between six and twelve months.
      Systemic therapeutic approaches for metastatic melanoma include chemotherapy,
      immunotherapy, immunochemotherapy, small molecules and targeted therapy. In this
      review, we will focus on the various treatment modalities as well as new agents
      used for targeted therapy. 

PMID- 24281102
TI  - VEGF and pleiotrophin modulate the immune profile of breast cancer.
AB  - Angiogenesis, the sprouting of the existing vascular network to form new vessels,
      is required for the growth of solid tumors. For this reason, the primary
      stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an
      attractive target for tumor therapy. In fact, there are currently numerous anti
      VEGF therapies in clinical development for the treatment of various cancers,
      including breast cancer. VEGF signals through two primary VEGF receptors, VEGFR1
      and VEGFR2. VEGFR2 is the primary angiogenic receptor, and VEGFR1 has been
      implicated in macrophage chemotaxis and tumor cell survival and invasion. It has
      only been appreciated recently that the VEGFRs are expressed not only on
      endothelial cells and tumor cells but also on many host immune cells. Therefore,
      to better understand the effects of anti-VEGF therapy it is important to consider
      the effects of VEGF on all cells in the tumor microenvironment, including immune
      cells. Bevacizumab (Avastin(r), Genetech), which binds VEGF and inhibits
      interaction with VEGFR1 and VEGFR2, was approved for the treatment of metastatic
      HER2/NEU-negative breast cancer in 2008, however, the majority of human mammary
      tumors are either innately resistant or will acquire resistance to anti-VEGF
      therapy. This suggests that these tumors activate alternate angiogenesis
      pathways. Pleiotrophin (PTN) is an important angiogenic cytokine in breast cancer
      and is expressed at high levels in approximately 60% of human breast tumors. PTN
      functions as an angiogenic factor and promotes remodeling of the tumor
      microenvironment as well as epithelial-mesenchymal transition (EMT). In addition,
      PTN can have profound effects on macrophage phenotype. The present review focuses
      on the functions of VEGF and PTN on immune cell infiltration and function in
      breast cancer. Furthermore, we will discuss how anti-VEGF therapy modulates the
      immune cell profile. 

PMID- 24281103
TI  - Wnt and related signaling pathways in melanomagenesis.
AB  - Given the pivotal roles of morphogen pathways including Wnt, Notch, Hedgehog, and
      BMP pathways in the development of the neural crest lineage, it is not surprising
      that these signaling networks have also been implicated in the biology of
      malignant melanoma. Understanding the mechanisms by which these pathways can
      alter cell fate and other biological properties in tumor cells will be essential
      for determining whether the therapeutic targeting of these pathways has a
      potential role in melanoma treatment. This review highlights some of the recent
      findings with regards to how morphogen signaling may regulate melanoma cell
      biology. 

PMID- 24281100
TI  - Predictive and prognostic protein biomarkers in epithelial ovarian cancer:
      recommendation for future studies.
AB  - Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its
      lack of symptoms, this disease is diagnosed at an advanced stage when the cancer
      has already spread to secondary sites. While initial rates of response to first
      treatment is >80%, the overall survival rate of patients is extremely low, mainly
      due to development of drug resistance. To date, there are no reliable clinical
      factors that can properly stratify patients for suitable chemotherapy strategies.
      Clinical parameters such as disease stage, tumor grade and residual disease,
      although helpful in the management of patients after their initial surgery to
      establish the first line of treatment, are not efficient enough. Accordingly,
      reliable markers that are independent and complementary to clinical parameters
      are needed for a better management of these patients. For several years, efforts
      to identify prognostic factors have focused on molecular markers, with a large
      number having been investigated. This review aims to present a summary of the
      recent advances in the identification of molecular biomarkers in ovarian cancer
      patient tissues, as well as an overview of the need and importance of molecular
      markers for personalized medicine in ovarian cancer. 

PMID- 24281104
TI  - Molecular mechanisms involved in the antitumor activity of cannabinoids on
      gliomas: role for oxidative stress.
AB  - Cannabinoids, the active components of Cannabis sativa, have been shown to exert
      antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and
      tissues. Of interest, cannabinoids have displayed great potency in reducing the
      growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro
      or in animal experimental models curbing the growth of xenografts generated by
      subcutaneous or intrathecal injection of glioma cells in immune-deficient mice.
      Cannabinoids appear to be selective antitumoral agents as they kill glioma cells
      without affecting the viability of non-transformed cells. This review will
      summarize the anti-cancer properties that cannabinoids exert on gliomas and
      discuss their potential action mechanisms that appear complex, involving
      modulation of multiple key cell signaling pathways and induction of oxidative
      stress in glioma cells. 

PMID- 24281105
TI  - Blood-based biomarkers for the optimization of anti-angiogenic therapies.
AB  - The dependence of tumor growth and metastasis on blood vessels makes tumor
      angiogenesis a rational target for therapy. Strategies have been pursued to
      inhibit neovascularization and to destroy existing tumor vessels, or both. These
      include direct targeting of endothelial cells, and indirect targeting by
      inhibiting the release of proangiogenic growth factors by cancer or stromal
      cells. Many patients benefit from antiangiogenic therapies; thus, development of
      noninvasive biomarkers of disease response and relapse is a crucial objective to
      aid in their management. A number of non-invasive tools are described with their
      potential benefits and limitations. We review currently available candidate
      biomarkers of anti-angiogenic agent effect. Including these markers into clinical
      trials may provide insight into appropriate dosing for desired biological
      effects, appropriate timing of additional therapy, and prediction of individual
      response. This has important consequences for the clinical use of angiogenesis
      inhibitors and for drug discovery, not only for optimizing the treatment of
      cancer, but possibly also for developing therapeutic approaches for various other
      diseases. 

PMID- 24281108
TI  - Studies on the non-protein thiols of a human prostatic cancer cell line:
      glutathione content.
AB  - The low molecular weight thiol (-SH) content of a human prostate carcinoma cell
      line (LNCap), important to the cellular resistance to drugs and irradiation, was
      investigated using three forms of thiol assay each utilizing different
      chemistries. The composition of the mixture was examined by derivatization of the
      thiols with a three-fold excess of the Ellman reagent to give mixed aromatic
      disulfides. The components were isolated by chromatography on C18 reverse phase
      silica gel followed by DE52 anion exchange separation, and then analyzed by
      capillary electrophoresis against prepared standards. The glutathione adduct
      (GSSE) and an unknown disulfide (RSSE) were the major components isolated on DE52
      together with two minor ones. However, from the absorbance at 325 nm, it was
      found that the GSSE isolated (1.5 +/- 0.2 femtomoles/cell) could only account for
      28.5 +/- 4.3% of the total ASF thiols. It appeared that the bulk of the thiol
      material had not formed a stable mixed disulfide with Ellman's reagent, and this
      was confirmed by 35S labeling of the cells. A large proportion of the 35S labeled
      components, obtained after reaction of the ASF thiols with the Ellman reagent,
      did not form mixed aromatic disulfides and could therefore not be identified by
      this labeling method. 

PMID- 24281106
TI  - Biomarkers for Basal-like Breast Cancer.
AB  - Initially recognized through microarray-based gene expression profiling, basal
      like breast cancer, for which we lack effective targeted therapies, is an
      aggressive form of carcinoma with a predilection for younger women. With some
      success, immunohistochemical studies have attempted to reproduce the expression
      profile classification of breast cancer through identification of subtype
      specific biomarkers. This review aims to present an in depth summary and analysis
      of the current status of basal-like breast cancer biomarker research. While a
      number of biomarkers show promise for future clinical application, the next
      logical step is a comprehensive investigation of all biomarkers against a gene
      expression profile gold standard for breast cancer subtype assignment. 

PMID- 24281107
TI  - Reinventing diagnostics for personalized therapy in oncology.
AB  - Human cancers are still diagnosed and classified using the light microscope. The
      criteria are based upon morphologic observations by pathologists and tend to be
      subject to interobserver variation. In preoperative biopsies of non-small cell
      lung cancers, the diagnostic concordance, even amongst experienced pulmonary
      pathologists, is no better than a coin-toss. Only 25% of cancer patients, on
      average, benefit from therapy as most therapies do not account for individual
      factors that influence response or outcome. Unsuccessful first line therapy costs
      Canada CAN$1.2 billion for the top 14 cancer types, and this extrapolates to $90
      billion globally. The availability of accurate drug selection for personalized
      therapy could better allocate these precious resources to the right therapies.
      This wasteful situation is beginning to change with the completion of the human
      genome sequencing project and with the increasing availability of targeted
      therapies. Both factors are giving rise to attempts to correlate tumor
      characteristics and response to specific adjuvant and neoadjuvant therapies.
      Static cancer classification and grading systems need to be replaced by
      functional classification systems that not only account for intra- and inter-
      tumor heterogeneity, but which also allow for the selection of the correct
      chemotherapeutic compounds for the individual patient. In this review, the
      examples of lung and breast cancer are used to illustrate the issues to be
      addressed in the coming years, as well as the emerging technologies that have
      great promise in enabling personalized therapy. 

PMID- 24281109
TI  - Serum tumor markers in pancreatic cancer-recent discoveries.
AB  - The low prevalence of pancreatic cancer remains an obstacle to the development of
      effective screening tools in an asymptomatic population. However, development of
      effective serologic markers still offers the potential for improvement of
      diagnostic capabilities, especially for subpopulations of patients with high risk
      for pancreatic cancer. The accurate identification of patients with pancreatic
      cancer and the exclusion of disease in those with benign disorders remain
      important goals. While clinical experience largely dismissed many candidate
      markers as useful markers of pancreatic cancer, CA19-9 continues to show promise.
      The present review highlights the development and the properties of different
      tumor markers in pancreatic cancer and their impact on the diagnostic and
      treatment of this aggressive disease. 

PMID- 24281111
TI  - Different serotonergic expression in nevomelanocytic tumors.
AB  - The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play
      a role in tumor progression. Thus, the aim of the present investigation was to
      determine whether alterations in the serotonergic system occur in nevomelanocytic
      tumors. For this purpose, paraffin-embedded biopsies of superficial spreading
      malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi
      (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and
      5-HT2A receptors, and the serotonin transporter protein (SERT), by
      immunohistochemical analysis. Melanocytes in the region surrounding the tumor
      were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that
      immunostained positively for the different serotonergic markers were observed in
      the suprabasal epidermis of DN tissue and, to an even greater extent, in the case
      of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5
      HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for
      SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor
      cell staining in the dermis for 5-HT1AR and SERT declined. Vessel
      immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to
      dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into
      the dermal region of the tumor, this infiltration being more evident in the case
      of DN and SSM. These latter cells were also tryptase-positive, indicating that
      they are mast cells. Thus, alterations in serotonergic system may be involved in
      nevomelanocytic tumors and mast cells may play an important role in this
      connection. 

PMID- 24281110
TI  - Markers for detection of prostate cancer.
AB  - Early detection of prostate cancer is problematic, not just because of
      uncertainly whether a diagnosis will benefit an individual patient, but also as a
      result of the imprecise and invasive nature of establishing a diagnosis by
      biopsy. Despite its low sensitivity and specificity for identifying patients
      harbouring prostate cancer, serum prostate specific antigen (PSA) has become
      established as the most reliable and widely-used diagnostic marker for this
      condition. In its wake, many other markers have been described and evaluated.
      This review focuses on the supporting evidence for the most prominent of these
      for detection and also for predicting outcome in prostate cancer. 

PMID- 24281112
TI  - Outpatient Follow-up and Secondary Prevention for Melanoma Patients.
AB  - Health care providers and their patients jointly participate in melanoma
      prevention, surveillance, diagnosis, and treatment. This paper reviews screening
      and follow-up strategies for patients who have been diagnosed with melanoma,
      based on current available evidence, and focuses on methods to assess disease
      recurrence and second primary occurrence. Secondary prevention, including the
      roles of behavioral modification and chemoprevention are also reviewed. The role
      of follow-up dermatologist consultation, with focused physical examinations
      complemented by dermatoscopy, reflectance confocal microscopy, and/or full-body
      mapping is discussed. Furthermore, we address the inclusion of routine imaging
      and laboratory assessment as components of follow-up and monitoring of advanced
      stage melanoma. The role of physicians in addressing the psychosocial stresses
      associated with a diagnosis of melanoma is reviewed. 

PMID- 24281114
TI  - Significance of micrometastases: circulating tumor cells and disseminated tumor
      cells in early breast cancer.
AB  - Adjuvant systemic therapy targets minimal residual disease. Our current clinical
      approach in the adjuvant setting is to presume, rather than confirm, the presence
      of minimal residual disease. Based on assessment of the primary tumor, we
      estimate an individual's recurrence risk. Subsequent treatment decisions are
      based on characteristics of the primary tumor, with the presumption of consistent
      biology and treatment sensitivity between micrometastases and the primary lesion.
      An alternative approach is to identify micrometastatic disease. Detection of
      disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells
      (CTC) from peripheral blood collection may offer quantification and
      biocharacterization of residual disease. This paper will review the prognostic
      and predictive potential of micrometastatic disease in early breast cancer. 

PMID- 24281113
TI  - Inflammatory genetic markers of prostate cancer risk.
AB  - Prostate cancer is the most common cancer in Western society males, with
      incidence rates predicted to rise with global aging. Etiology of prostate cancer
      is however poorly understood, while current diagnostic tools can be invasive
      (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate
      specific antigen (PSA) testing). Substantial histological, epidemiological and
      molecular genetic evidence indicates that inflammation is important in prostate
      cancer pathogenesis. In this review, we summarize the current status of
      inflammatory genetic markers influencing susceptibility to prostate cancer. The
      focus will be on inflammatory cytokines regulating T-helper cell and chemokine
      homeostasis, together with the Toll-like receptors as key players in the host
      innate immune system. Although association studies indicating a genetic basis for
      prostate cancer are presently limited mainly due to lack of replication, larger
      and more ethnically and clinically defined study populations may help elucidate
      the true contribution of inflammatory gene variants to prostate cancer risk. 

PMID- 24281115
TI  - Circulating tumor cells, enumeration and beyond.
AB  - The detection and enumeration of circulating tumor cells (CTCs) has shown
      significant clinical utility with respect to prognosis in breast, colorectal and
      prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic
      information to aid therapy decision making. CTCs as a 'virtual and real-time
      biopsy' have clear potential to facilitate exploration of tumor biology, and in
      particular, the process of metastasis. The challenge of profiling CTC molecular
      characteristics and generating CTC signatures using current technologies is that
      they enrich rather than purify CTCs from whole blood; we face the problem of
      looking for the proverbial 'needle in the haystack'. This review summarizes the
      current methods for CTC detection and enumeration, focuses on molecular
      characterization of CTCs, unveils some aspects of CTC heterogeneity, describes
      attempts to purify CTCs and scans the horizon for approaches leading to
      comprehensive dissection of CTC biology. 

PMID- 24281116
TI  - Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin.
AB  - A main feature of cancer cells, when compared to normal ones, is a persistent pro
      oxidative state that leads to an intrinsic oxidative stress. Cancer cells have
      higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in
      turn, responsible for the maintenance of the cancer phenotype. Persistent ROS
      stress may induce adaptive stress responses, enabling cancer cells to survive
      with high levels of ROS and maintain cellular viability. However, excessive ROS
      levels render cancer cells highly susceptible to quercetin, one of the main
      dietary flavonoids. Quercetin depletes intracellular glutathione and increases
      intracellular ROS to a level that can cause cell death. 

PMID- 24281117
TI  - Serum biomarkers for early detection of gynecologic cancers.
AB  - Ovarian, endometrial, and cervical cancers are three of the most common
      malignancies of the female reproductive organs. CA 125, historically the most
      reliable serum marker for ovarian cancer, is elevated in 50% of early-stage
      ovarian tumors. For endometrial cancers, there are no established serum markers.
      SCC, which is the best studied serum marker for squamous cell carcinomas, has
      been unreliable; SCC is elevated in cervical squamous cell carcinomas ranging
      from 28-85% of the time. Recent proteomics-based analyses show great promise for
      the discovery of new and more useful biomarkers. In this review, we will discuss
      the currently utilized serum tumor markers for gynecologic cancers and the novel
      biomarkers that are now under investigation. 

PMID- 24281118
TI  - Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small,
      regulatory non-coding RNAs that inhibit gene expression at the post
      transcriptional level in a sequence-specific manner. Each miRNA represses the
      protein expression of several coding genes in a manner proportional to the
      sequence complementarity with the target transcripts. MicroRNAs play key
      regulatory roles in organismal development and homeostasis. They control
      fundamental biological processes, such as stem-cell regulation and cellular
      metabolism, proliferation, differentiation, stress resistance, and apoptosis.
      Differential miRNA expression is found in malignant tumors in comparison to
      normal tissue counterparts. This indicates that miRNA deregulation contributes to
      the initiation and progression of cancer. Currently, miRNA expression signatures
      are being rigorously investigated in various tumor types, with the aim of
      developing novel, efficient biomarkers that can improve clinical management of
      cancer patients. This review discusses deregulated miRNAs in solid tumors, and
      focuses on their emerging prognostic potential. 

PMID- 24281120
TI  - Surgical procedure joining the lateral rectus and superior rectus muscles with or
      without medial rectus recession for the treatment of strabismus associated with
      high myopia.
AB  - PURPOSE: To evaluate the outcomes of a surgical procedure involving the muscle
      union of the superior rectus (SR) and lateral rectus (LR) muscles with or without
      medial rectus (MR) recession for the treatment of strabismus associated with high
      myopia and the anatomic changes from before and after surgery. METHODS: Thirty
      five eyes of 20 patients who had undergone a muscle union of the SR and LR
      muscles with or without MR recession for treatment of acquired strabismus
      associated with an inferior displacement of the LR and nasal displacement of the
      SR in magnetic resonance imaging of the orbit due to axial high myopia were
      observed prospectively. Main outcome measures were the angles of the dislocation
      of the globe, angles of horizontal or vertical deviations, abductions, and
      supraductions. The angles of the dislocation of the globe were analyzed using
      magnetic resonance imaging (1.5 Tesla Magnet; Siemens Symphonia, Munich,
      Germany). RESULTS: The axial lengths ranged from 26 to 36 mm (mean: 30.6 +/- 2.8
      mm). The angle of dislocation of the globe changed from 178o +/- 10o to 101o +/-
      6o, the angle of esotropia changed from 58.6 +/- 2.5 to 6.8 +/- 1.4 prism
      diopters (PD); and the angle of hypotropia changed from 12.5 +/- 1.3 to 3.3 +/-
      1.1 PD postoperatively. Abduction and supraduction improved significantly after
      surgery. At the 4-year follow-up, the postoperative outcomes were stable.
      CONCLUSIONS: In the treatment of strabismus caused by high myopia, the surgical
      procedure involving the muscle union of the SR and LR muscles with or without MR
      recession was effective on both the restoration of the dislocated globe into the
      muscle cone and the improvement of ocular motility.

PMID- 24281119
TI  - The nrf1 and nrf2 balance in oxidative stress regulation and androgen signaling
      in prostate cancer cells.
AB  - Reactive oxygen species (ROS) signaling has recently sparked a surge of interest
      as being the molecular underpinning for cancer cell survival, but the precise
      mechanisms involved have not been completely elucidated. This review covers the
      possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the
      antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in
      modulating AR expression and signaling in aggressive prostate cancer (PCa) cells.
      In androgen independent (AI) C4-2B cells, in comparison to the parental androgen
      dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression
      and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT
      treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1
      correlated with enhanced AR transactivation. Our findings implicate a crucial
      balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells.
      Here we will discuss how understanding the mechanisms by which oxidative stress
      may affect AR signaling may aid in developing novel therapies for AI-PCa. 

PMID- 24281121
TI  - Ninety-day survival of a calf implanted with a continuous-flow total artificial
      heart.
AB  - We evaluated the effects of steady state flow and perfusion on end-organ function
      in a long-term calf model. The animal received a continuous-flow total artificial
      heart (CFTAH) that we created from two axial-flow ventricular assist devices.
      Pump flow, blood pressure, and other pump parameters were monitored throughout
      the study, as were arterial blood gas and hematologic values, including
      neurohormone levels. Some hematologic values were mildly abnormal transiently
      after surgery but returned to acceptable levels within the first week. During the
      90-day study, the calf showed no signs of hemolysis or thrombosis. Its mental
      function remained normal, as evidenced by the animal's interest in its
      surroundings and response to stimuli. End-organ and vasomotor function was not
      adversely affected by 90 days of steady state flow. This was the first study in
      which CFTAH support of an animal model was maintained for this duration. 

PMID- 24281122
TI  - Eight-year experience with a continuous-flow total artificial heart in calves.
AB  - Over the last 8 years, we have developed and evaluated a continuous-flow total
      artificial heart (CFTAH) comprising two rotary blood pumps. To understand the
      physiologic effects of nonpulsatile circulation, we evaluated the CFTAH in 65
      calves for 90 days or less. We describe our experience with 29 calves that
      survived for 7 days or more. The calves received dual axial-flow (n = 24) or
      centrifugal-flow (n = 5) pumps. Several iterations of customized atrial cuffs
      were developed to facilitate an adequate anatomical fit. Pressures (arterial
      pressure [AoP], pulmonary artery pressure [PAP], left atrial pressure [LAP], and
      right atrial pressure [RAP]) and pump parameters were continuously monitored.
      Hematologic and biochemistry values were analyzed. After each case, a necropsy
      was performed. The calves survived for 7-92 days (mean, 24 days). Pressures were
      94 +/- 14 (AoP), 25 +/- 8 (PAP), 14 +/- 6 (RAP), and 16 +/- 6 (LAP) mm Hg. Pump
      flow was maintained at 9.1 +/- 1.7 L/minute (right) and 9.4 +/- 1.9 L/minute
      (left). Hematologic and biochemistry values remained acceptable. Eight animals
      underwent treadmill evaluations, in which oxygen consumption (VO2) was comparable
      with physiologic total-body VO2. In the two animals that survived to 90 days, the
      end-organs appeared unremarkable at autopsy, and the CFTAH circuits were free of
      thrombus. Our results show that a CFTAH can maintain a large animal
      physiologically and hemodynamically for up to 90 days with continuous flow. 

PMID- 24281123
TI  - Successful use of extracorporeal membrane oxygenation for respiratory failure in
      pulmonary chronic graft-versus-host disease.
AB  - Pulmonary complications of hematopoietic stem cell transplantation (HSCT) are
      responsible for significant morbidity and mortality. There is no literature to
      date on the use of extracorporeal membranous oxygenation (ECMO) in patients with
      pulmonary manifestations of chronic graft-versus-host disease after HSCT. We
      describe the successful use of ECMO for refractory respiratory failure in such a
      patient. 

PMID- 24281124
TI  - Arteriovenous fistula survival with buttonhole (constant site) cannulation for
      hemodialysis access.
AB  - Buttonhole needling for arteriovenous fistulae (AVF) has increased in popularity
      among dialysis centers. Concerns have been raised about the risks of infection,
      so we reviewed our experience of buttonhole needling in 227 adult patients on
      hemodialysis. The mean buttonhole AVF survival was 27.0 months, in 227 patients,
      61.1% male, mean age 63.8 +/- 15.5 years, 45.8% with diabetes mellitus, median
      dialysis vintage 19 months (6.5-42.8). Ninety-six patients transferred to rope
      ladder AVF cannulation, because of cannulation failure in 25%, persistent
      bleeding at the needling site in 24%, fistula thrombosis in 14%, and infections
      in 15%. Because of persistent methicillin-sensitive Staphylococcus aureus (MSSA)
      or methicillin-resistant S. aureus (MRSA) colonization, 18.8% discontinued
      buttonhole needling. Transfer from buttonhole needling was more common for people
      with diabetes (X = 6.57; p = 0.035), older patients (odds ratio, 0.985; p =
      0.007), and persistent MSSA/MRSA colonization (odds ratio, 0.88; p = 0.037).
      Eleven episodes of suspected buttonhole S. aureus bacteremia occurred giving a
      bacteremia rate of 2.94 per 100 patient years, and 15 local infections giving an
      infection rate of 4.01 per 100 patient years. In this large series of buttonhole
      AVF access, although infection rates were increased, more patients discontinued
      buttonhole needling because of technical cannulation problems and persistent
      bleeding from needle tracks. 

PMID- 24281125
TI  - Complete response of primary bladder adenocarcinoma with the FOLFOX4 regimen.
AB  - INTRODUCTION: Primary adenocarcinoma of the bladder is a very rare disease that
      is difficult to treat. In this paper, we report the second case in the literature
      with primary mucinous adenocarcinoma of the bladder which showed complete
      response to FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) chemotherapy regimen.
      CASE REPORT: A 41-year-old man was admitted to our hospital with a diagnosis of
      primary adenocarcinoma of the bladder. Due to the similarity in histology with
      colon carcinoma, a FOLFOX4 regimen was started. Complete response was achieved at
      the end of this treatment. Today the patient is free of local or systemic
      disease. CONCLUSION: FOLFOX4 regimen may be a treatment option for primary
      adenocarcinoma of the bladder.

PMID- 24281126
TI  - The historical moment in the analysis of gay men.
AB  - The meanings of men's same-sex desire have changed rapidly in the last fifty
      years. As a result it is common that patients and analysts (or psychotherapists)
      have dissonant implicit understandings of the significance of this desire. This
      dissonance can have untoward clinical consequences, some of which are explored
      here, and may be partly mitigated to facilitate better analytic and
      psychotherapeutic work with gay men. 

PMID- 24281127
TI  - Ylide mediated carbonyl homologations for the preparation of isatin derivatives.
AB  - An exceptionally mild method for the preparation of isatin derivatives has been
      developed using a sulfur ylide mediated carbonyl homologation sequence starting
      from anthranilic acid precursors. This method proceeds at ambient temperature via
      a sulfur ylide intermediate without the need for protection of the amine or
      chromatographic isolation of the intermediate ylide. Gentle oxidation of the
      sulfur ylides provides isatin derivatives with N-H, N-alkyl, N-aryl substitution,
      electron-rich and electron-poor aromatic rings, and heterocyclic aromatic
      systems. We anticipate that this method will greatly expand the accessibility of
      complex isatin derivatives. 

PMID- 24281128
TI  - Association study of cathepsin D gene polymorphism in Iranian patients with
      sporadic late-onset Alzheimer's disease.
AB  - One of the most prevalent forms of dementia is Alzheimer's disease (AD). Complex
      inheritance and multifactorial patterns of late-onset AD (LOAD) along with its
      heterogeneity are due to the presence of different AD-predisposing genes with
      different influence on disease development among various populations. A key event
      in the pathogenesis of AD is the deposition of beta-amyloid peptide, which is
      derived from the amyloid precursor protein by beta- and gamma-secretases.
      Cathepsin D (CTSD) is an acid protease with beta- and gamma-secretase-like
      features in vitro. An exonic C->T polymorphism at position 224 of the CTSD gene
      (rs: 17571) has been shown to be associated with the enzyme function of CTSD and
      with AD. Two studies in the German population reported a strong association of
      this polymorphism with an increased risk of developing AD, while other studies
      did not confirm this observation. We tested for this association in a case
      control study in 100 Iranian sporadic LOAD patients based on diagnostic criteria
      of DSM-IV-TR and NINCDS-ADRDA and in 100 normal controls without any personal and
      family history of AD or other related dementias. Polymerase chain reaction
      restriction fragment length polymorphism was set up to detect this polymorphism.
      Our study demonstrated that T-carrying genotype frequency in AD patients is
      significantly higher than in controls and there was a 2.5-fold increased risk for
      developing AD in the T-carrying genotype compared to C/C genotype (odds ratio =
      2.5, p = 0.010). The odds ratio for subjects with the apolipoprotein E epsilon4
      (APOE epsilon4) allele was 2.91 (p = 0.003) and carriers of the CTSD T and APOE
      epsilon4 alleles had a 6.25-fold increased risk of the disease (p = 0.0). Our
      results indicate that CTSD genotype is associated with the disease and a
      combination of the above risk factors significantly alters the risk for
      developing AD.

PMID- 24281129
TI  - Evaluating New York City's abortion reporting system: insights for public health
      data collection systems.
AB  - CONTEXT: New York City (NYC) mandates reporting of all abortion procedures. These
      reports enable tracking of abortion incidence and underpin programs, policy, and
      research. Since January 2011, the majority of abortion facilities must report
      electronically. OBJECTIVES: We conducted an evaluation of NYC's abortion
      reporting system and its transition to electronic reporting. We summarize the
      evaluation methodology and results and draw lessons relevant to other vital
      statistics and public health reporting systems. DESIGN: The evaluation followed
      Centers for Disease Control and Prevention guidelines for evaluating public
      health surveillance systems. We interviewed key stakeholders and conducted a data
      provider survey. In addition, we compared the system's abortion counts with
      external estimates and calculated the proportion of missing and invalid values
      for each variable on the report form. Finally, we assessed the process for
      changing the report form and estimated system costs. SETTING: NYC Health
      Department's Bureau of Vital Statistics. MAIN OUTCOME MEASURES: Usefulness,
      simplicity, flexibility, data quality, acceptability, sensitivity, timeliness,
      and stability of the abortion reporting system. RESULTS: Ninety-five percent of
      abortion data providers considered abortion reporting important; 52% requested
      training regarding the report form. Thirty percent reported problems with
      electronic biometric fingerprint certification, and 18% reported problems with
      the electronic system's stability. Estimated system sensitivity was 88%. Of 17
      variables, education and ancestry had more than 5% missing values in 2010.
      Changing the electronic reporting module was costly and time-consuming. System
      operating costs were estimated at $80 136 to $89 057 annually. CONCLUSIONS: The
      NYC abortion reporting system is sensitive and provides high-quality data, but
      opportunities for improvement include facilitating biometric certification,
      increasing electronic platform stability, and conducting ongoing outreach and
      training for data providers. This evaluation will help data users determine the
      degree of confidence that should be placed on abortion data. In addition, the
      evaluation results are applicable to other vital statistics reporting and
      surveillance systems.

PMID- 24281130
TI  - The lateral thoracic artery revisited.
AB  - BACKGROUND: Although the variations in the origin of the branches of the axillary
      and subclavian arteries have been well documented, little information regarding
      the highly variable lateral thoracic artery (LTA) is available. Descriptions of
      the LTA variations may prove useful during procedures of the lateral aspects of
      the thorax such as reconstructive plastic surgery and modified radical
      mastectomy. PURPOSE: The aim of this study was to examine the anatomy of the LTA
      and offer an accurate account of its variability. METHODS: The entire course and
      distribution of the LTA was examined in 420 formalin-fixed adult human cadavers.
      RESULTS: The LTA was found in 96.7 % of the specimens, showing great
      morphological variability and classified into six types according to its origin.
      The most common type was where the LTA arose from the thoracoacromial artery
      (Type I 67.62 %). In decreasing order of incidence were origins from: the
      axillary artery (Type II 17.02 %), the thoracodorsal artery (Type III 5 %), and
      the subscapular artery (Type IV 3.93 %). Additionally, multiple LTAs were present
      (Type V 3.09 %) and complete absence of LTA (Type VI 3.33 %) was observed.
      CONCLUSION: Despite variations in origin of the vessels, our dissections
      demonstrated that the ultimate tissue distribution of the LTA remained typical in
      the vast majority of the specimens and descended on the lateral border of the
      pectoralis minor. Our results illustrate the need for re-evaluation of the
      branches of the thoracoacromial artery with possible consideration that the LTA
      arises from it, instead of directly from the axillary artery. We hope that the
      information supplied by this study will provide useful information to anatomists
      and surgeons alike.

PMID- 24281133
TI  - Recent advances in cooperative bimetallic asymmetric catalysis: dinuclear Schiff
      base complexes.
AB  - Cooperative catalysis has proven to be a powerful strategy for realizing high
      reactivity and selectivity in asymmetric transformations. A variety of
      cooperative asymmetric catalysts have been developed over the last two decades.
      In this feature article, recent advances from our research on cooperative
      asymmetric catalysis, focusing on dinuclear Schiff base catalysis, are described.
      Design of dinuclear Schiff base catalysts and their applications in several
      asymmetric C-C and C-N bond-forming reactions under simple proton transfer
      conditions with perfect atom-economy are discussed in detail. 

PMID- 24281132
TI  - Childhood leukaemia near nuclear power plants.

PMID- 24281134
TI  - Predictors of postdischarge outcomes from information acquired shortly after
      admission for acute heart failure: a report from the Placebo-Controlled
      Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline
      for Patients Hospitalized With Acute Decompensated Heart Failure and Volume
      Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT)
      Study.
AB  - BACKGROUND: Acute heart failure is a common reason for admission, and outcome is
      often poor. Improved prognostic risk stratification may assist in the design of
      future trials and in patient management. Using data from a large randomized
      trial, we explored the prognostic value of clinical variables, measured at
      hospital admission for acute heart failure, to determine whether a few selected
      variables were inferior to an extended data set. METHODS AND RESULTS: The
      prognostic model included 37 clinical characteristics collected at baseline in
      PROTECT, a study comparing rolofylline and placebo in 2033 patients admitted with
      acute heart failure. Prespecified outcomes at 30 days were death or
      rehospitalization for any reason; death or rehospitalization for cardiovascular
      or renal reasons; and, at both 30 and 180 days, all-cause mortality. No variable
      had a c-index>0.70, and few had values>0.60; c-indices were lower for composite
      outcomes than for mortality. Blood urea was generally the strongest single
      predictor. Eighteen variables contributed independent prognostic information, but
      a reduced model using only 8 items (age, previous heart failure hospitalization,
      peripheral edema, systolic blood pressure, serum sodium, urea, creatinine, and
      albumin) performed similarly. For prediction of all-cause mortality at 180 days,
      the model c-index using all variables was 0.72 and for the simplified model, also
      0.72. CONCLUSIONS: A few simple clinical variables measured on admission in
      patients with acute heart failure predict a variety of adverse outcomes with
      accuracy similar to more complex models. However, predictive models were of only
      moderate accuracy, especially for outcomes that included nonfatal events. Better
      methods of risk stratification are required. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458.

PMID- 24281135
TI  - Four-variable risk model in men and women with heart failure.
AB  - BACKGROUND: Risk stratification is an integral component of clinical decision
      making in heart failure (HF). Women with HF have unique characteristics compared
      with men, and it is unknown whether common prognostic factors are equally useful
      in both populations. We aimed to investigate whether sex-specific risk models are
      more accurate for risk prediction in patients with advanced HF. METHODS AND
      RESULTS: Patients with advanced HF referred to University of California, Los
      Angeles (UCLA; n=2255), were stratified by sex into derivation (referred in 2000
      2007) and validation (referred in 2008-2011) cohorts. Cox regression analysis was
      used to ascertain key variables predictive of the primary end point of
      death/urgent transplantation/ventricular assist device in the derivation cohorts
      and confirmed in the validation cohorts in men, women, and the total population.
      Women were younger, with higher ejection fraction and better event-free survival.
      Despite differences in baseline characteristics, the 4 strongest predictors of
      outcome in both women and men, as well as in the total cohort, were B-type
      natriuretic peptide, peak oxygen consumption by cardiopulmonary exercise testing
      (pkVO2), New York Heart Association (NYHA) classification, and use of angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker. In addition, the
      UCLA model performed better than the Seattle Heart Failure Model (SHFM) and the
      Heart Failure Survival Score (HFSS) in our cohort (c-indices of 0.791[UCLA]
      versus 0.758 [SHFM], 0.607 [noninvasive HFSS], and 0.625 [invasive HFSS]).
      CONCLUSIONS: A simple risk model assessing 4 clinical variables-B-type
      natriuretic peptide, pkVO2, NYHA, and angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker use-is well suited to provide prognostic
      information in both men and women with advanced HF.

PMID- 24281136
TI  - Guideline concordance of testing for hyperkalemia and kidney dysfunction during
      initiation of mineralocorticoid receptor antagonist therapy in patients with
      heart failure.
AB  - BACKGROUND: Mineralocorticoid receptor antagonists (MRA) reduce morbidity and
      mortality in heart failure with reduced ejection fraction but can cause
      hyperkalemia and acute kidney injury. Guidelines recommend measurement of serum
      potassium (K) and creatinine (Cr) before and serially after MRA initiation, but
      the extent to which this occurs is unknown. METHODS AND RESULTS: Using electronic
      data from 3 health systems 2005 to 2008, we performed a retrospective review of
      laboratory monitoring among 490 patients hospitalized for heart failure with
      reduced ejection fraction who were subsequently initiated on MRA therapy. Median
      age at time of MRA initiation was 73 years, and 37.1% were women. Spironolactone
      accounted for 99.4% of MRA use. Initial ambulatory MRA dispensing occurred at
      hospital discharge in 70.0% of cases. In the 30 days before MRA initiation, 94.3%
      of patients had a K or Cr measurement. Preinitiation K was >5.0 mmol/L in 1.4%
      and Cr>2.5 mg/dL in 1.7%. In the 7 days after MRA initiation among patients who
      remained alive and out of the hospital, 46.5% had no evidence of K measurement;
      by 30 days, 13.6% remained untested. Patient factors explained a small portion of
      postinitiation K testing (c-statistic, 0.67). CONCLUSIONS: Although laboratory
      monitoring before MRA initiation for heart failure with reduced ejection fraction
      is common, laboratory monitoring after MRA initiation frequently does not meet
      guideline recommendations, even in patients at higher risk for complications.
      Quality improvement efforts that encourage the use of MRA should also include
      mechanisms to address recommended monitoring.

PMID- 24281137
TI  - Renal function trajectories and clinical outcomes in acute heart failure.
AB  - BACKGROUND: Prior studies have demonstrated adverse risk associated with baseline
      and worsening renal function in acute heart failure, but none has modeled the
      trajectories of change in renal function and their impact on outcomes. METHODS
      AND RESULTS: We used linear mixed models of serial measurements of blood urea
      nitrogen and creatinine to describe trajectories of renal function in 1962
      patients with acute heart failure and renal dysfunction enrolled in the Placebo
      Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist
      Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and
      Volume Overload to Assess Treatment Effect on Congestion and Renal Function
      study. We assessed risk of 180-day mortality and 60-day cardiovascular or renal
      readmission and used Cox regression to determine association between renal
      trajectories and outcomes. Compared with patients alive at 180 days, patients who
      died were older, had lower blood pressure and ejection fraction, and higher
      creatinine levels at baseline. On average for the entire cohort, creatinine rose
      from days 1 to 3 and increased further after discharge, with the trajectory
      dependent on the day of discharge. Blood urea nitrogen, creatinine, and the rate
      of change in creatinine from baseline were the strongest independent predictors
      of 180-day mortality and 60-day readmission, whereas the rate of change of blood
      urea nitrogen from baseline was not predictive of outcomes. Baseline blood urea
      nitrogen>35 mg/dL and increase in creatinine>0.1 mg/dL per day increased the risk
      of mortality, whereas stable or decreasing creatinine was associated with reduced
      risk. CONCLUSIONS: Patients with acute heart failure and renal dysfunction
      demonstrate variable rise and fall in renal indices during and immediately after
      hospitalization. Risk of morbidity and mortality can be predicted based on
      baseline renal function and creatinine trajectory during the first 7 days.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifiers: NCT00328692 and NCT00354458.

PMID- 24281138
TI  - Elaboration and characterization of barley protein nanoparticles as an oral
      delivery system for lipophilic bioactive compounds.
AB  - This is the first report in which barley protein nanoparticles were prepared with
      the aim of developing a delivery system for lipophilic bioactive compounds at
      ambient temperature using high pressure homogenization. No organic solvents or
      crosslinking reagents were involved in the nanoparticle preparation. Effects of
      processing conditions and formulae on particle size and size distribution were
      investigated. Optimal nanoparticles with regular spherical shape, small size (90
      150 nm) and narrow size distribution (PDI < 0.3) could be achieved at a protein
      weight concentration of up to 5% when the oil/protein ratio was maintained within
      a range of 1 to 1.5. These nanoparticles exhibited high zeta-potential (about -35
      mV), high payload (51.4-54.5%) and good stability without the use of surfactants.
      As shown by the release test, though the bulk protein matrices of nanoparticles
      were degraded in the simulated gastric tract, even smaller nanoparticles were
      released and bioactive compounds were protected by a layer of barley protein.
      Then, complete release occurred in the simulated intestinal environments due to
      pancreatin degradation. In vitro studies showed that barley protein nanoparticles
      are relatively safe and could be internalized by Caco-2 cells and accumulated in
      the cytoplasm. 

PMID- 24281139
TI  - Components of the metabolic syndrome in early childhood in very-low-birth-weight
      infants.
AB  - BACKGROUND/AIMS: Term small-for-gestational-age and preterm born infants have an
      increased prevalence of metabolic syndrome components already in childhood. Data
      in very-low-birth-weight (VLBW) children are limited. We investigated the
      prevalence of metabolic syndrome components in VLBW infants at 2 years of
      corrected age. METHODS: We included 38 children, participating in the Neonatal
      Insulin Replacement Therapy in Europe (NIRTURE) trial, a randomized controlled
      trial of early insulin therapy in VLBW infants. Metabolic syndrome components
      were defined as: body mass index SDS >2; blood pressure (systolic and/or
      diastolic) >= 90th percentile; triglycerides >= 0.98 mmol/l; high-density
      lipoprotein (HDL) cholesterol <= 1.03 mmol/l; glucose >= 5.6 mmol/l. RESULTS: Two
      children (5%) had three metabolic syndrome components, 13 children (34%) had two
      components, and 11 children (29%) one component. 63% had raised blood pressure
      (prevalence higher in boys), 32% low HDL, and 30% high triglycerides (prevalence
      lower in early insulin group). In children with body mass index SDS <0, insulin
      treated children had higher HDL than children with standard care. Systolic blood
      pressure was correlated with growth between term and 2 years of corrected age.
      CONCLUSIONS: VLBW infants already have a high prevalence of metabolic syndrome
      components at 2 years of corrected age. Early insulin treatment could have long
      term benefits for some of these components.

PMID- 24281140
TI  - Intestinal Na+ loss and volume depletion in JAK3-deficient mice.
AB  - BACKGROUND/AIMS: The Janus kinase 3 JAK3 participates in the signaling of immune
      cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been
      shown to affect intestinal activity of the epithelial Na(+) channel ENaC and thus
      colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3
      deficient mice could lead to intestinal salt loss compromizing extracellular
      volume maintenance and blood pressure regulation. The present study thus explored
      whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na(+) exretion,
      blood pressure and extracellular fluid volume regulation. METHODS: Experiments
      were performed in gene-targeted mice lacking functional JAK3 (jak3(-/-)) and in
      wild type mice (jak3(+/+)). Colonic ENaC activity was estimated from amiloride
      sensitive current in Ussing chamber experiments, fecal, serum and urinary Na(+)
      concentration by flame photometry, blood pressure by the tail cuff method and
      serum aldosterone levels by immunoassay. RESULTS: The amiloride (50 uM)-induced
      deflection of the transepithelial potential difference was significantly lower
      and fecal Na(+) excretion significantly higher in jak3(-/-) mice than in
      jak3(+/+) mice. Moreover, systolic arterial blood pressure was significantly
      lower and serum aldosterone concentration significantly higher in jak3(-/-) mice
      than in jak3(+/+) mice. Both, absolute and fractional renal Na(+) excretion were
      significantly lower in jak3(-/-) mice than in jak3(+/+) mice. CONCLUSIONS: JAK3
      deficiency leads to impairment of colonic ENaC activity with intestinal Na(+)
      loss, decrease of blood pressure, increased aldosterone release and subsequent
      stimulation of renal tubular Na(+) reabsorption.

PMID- 24281141
TI  - Neuropathology of cortical superficial siderosis and cerebral amyloid angiopathy:
      new insights, new questions.

PMID- 24281142
TI  - Morphology and electrostatics play active role in neuronal differentiation
      processes on flexible conducting substrates.
AB  - This commentary discusses and summarizes the key highlights of our recently
      reported work entitled "Neuronal Differentiation of Embryonic Stem Cell Derived
      Neuronal Progenitors Can Be Regulated by Stretchable Conducting Polymers." The
      prospect of controlling the mechanical-rigidity and the surface conductance
      properties offers a unique combination for tailoring the growth and
      differentiation of neuronal cells. We emphasize the utility of transparent
      elastomeric substrates with coatings of electrically conducting polymer to
      realize the desired substrate-characteristics for cellular development processes.
      Our study showed that neuronal differentiation from ES cells is highly influenced
      by the specific substrates on which they are growing. Thus, our results provide a
      better strategy for regulated neuronal differentiation by using such functional
      conducting surfaces. 

PMID- 24281143
TI  - Supramolecular chains of high nuclearity {Mn(III)25} barrel-like single molecule
      magnets.
AB  - The first application of 1-methyl-1H-pyrrole-2-carbaldehyde oxime as a ligand for
      the coordination of paramagnetic transition metal ions has afforded a new
      {Mn(III)25} barrel-like cluster linked via Na(+) cations into a 1D polymeric
      topology that exhibits single-molecule magnetic behaviour. 

PMID- 24281144
TI  - Genomics: Organ roles for mitochondrial mutations?

PMID- 24281145
TI  - Gene regulation: RNA methylation regulates the circadian clock.

PMID- 24281146
TI  - Corrigendum: Advanced genetic tools for plant biotechnology.

PMID- 24281147
TI  - Development: Sharing enhancers for a different outcome.

PMID- 24281149
TI  - The independence of medical journals and the deceptive effects of open access.

PMID- 24281148
TI  - Bacterial genome sequencing in the clinic: bioinformatic challenges and
      solutions.
AB  - The potential of bacterial whole-genome sequencing (WGS) to complement existing
      diagnostic infrastructures in clinical microbiology has been shown in proof-of
      principle examples and extensively discussed. However, less attention has been
      drawn to bioinformatic challenges that are associated with the clinical adoption
      of WGS-based molecular diagnostics. This Perspective article discusses questions
      that are related to standard operating procedures, computational resource
      management, and data storage and integration in the context of recent
      developments in the sequencing and bioinformatics service markets.

PMID- 24281150
TI  - Clinical efficacy of infliximab in moderate to severe ulcerative colitis in a
      latin american referral population.
AB  - BACKGROUND: Previous research has shown that infliximab (IFX) is effective in the
      management of moderate to severe active ulcerative colitis (UC). Latin American
      studies are lacking. AIM: To evaluate the efficacy of IFX treatment (including
      corticosteroid withdrawal, complete mucosal healing, colectomy and
      hospitalization rates) in patients with moderate to severe UC. METHODS: A
      retrospective and descriptive study was conducted on patients with UC in Medellin
      (Colombia). We included patients steroid dependent or refractory to conventional
      treatment. RESULTS: Between October 2005 and July 2011, 28 patients with moderate
      to severe UC received IFX infusions; the median of the follow-up was 27.4 months
      (range: 1-69 months). Twenty-four patients (86%) had a short-term primary
      response, whilst 19 (68%) achieved initial clinical remission. After 1 year, 17
      (71%) out of the 24 patients who had an initial response were also showing a
      sustained response, and 10 (42%) remained in clinical remission. At 6 months,
      complete mucosal healing was observed in 29% of patients and endoscopic
      improvement in 57%. CONCLUSIONS: This is the first study to evaluate the IFX use
      in patients with moderate to severe active UC in a Latin American population. We
      found that IFX therapy is effective for inducing clinical remission, and that
      most patients who had an initial response showed a long-term sustained response.

PMID- 24281151
TI  - Screening for depressed mood in patients with cancer using the MD Anderson
      Symptom Inventory: investigation of a practical approach for the oncologist.
AB  - PURPOSE: Depression is a significant concern in outpatient oncology care, yet
      clinicians face practical challenges in accurately and efficiently screening
      patients for it. This study investigated whether a single item or multiple items
      from an existing multisymptom scale, the MD Anderson Symptom Inventory (MDASI),
      might serve as effective initial screens for depressed mood. METHODS: Data were
      collected from two cohorts of patients. Cohort 1 comprised 187 patients with non
      small-cell lung cancer who completed the Beck Depression Inventory II; cohort 2
      comprised 281 patients with renal cell carcinoma who completed the Center for
      Epidemiologic Studies Depression Scale. All patients completed the MDASI. Single
      item and multiple-item MDASI solutions were identified using cohort 1 and
      validated in cohort 2. Sensitivity and specificity of the solutions were assessed
      through binary linear regression; cut points were identified using receiver
      operating characteristic analysis. RESULTS: The MDASI single item "sadness" was
      the best solution identified in cohort 1 for screening for depressed mood
      relative to other affective items (distress, enjoyment of life, mood). At a cut
      point >= 4 (0 to 10 scale), the "sadness" item exhibited a clinically acceptable
      specificity of 81.5%, sensitivity of 72.0%, a negative predictive value of 95.0%,
      and a positive predictive value of 37.5%. This solution was successfully
      validated in cohort 2. CONCLUSION: The MDASI "sadness" item has modest
      sensitivity and high negative predictive value and can serve as a useful initial
      screen for depressed mood. This approach may improve the efficiency and
      acceptability of depression screening for both clinicians and patients.

PMID- 24281152
TI  - Real-world outcomes in metastatic renal cell carcinoma: insights from a Joint
      Community-Academic Registry.
AB  - INTRODUCTION: As new therapeutics for metastatic renal cell carcinoma (mRCC) are
      quickly introduced to market, comparative randomized trial evidence guiding
      treatment decisions is lacking, especially in the second treatment exposure and
      beyond. As a demonstration case, we studied mRCC in real-world clinical settings
      by creating a joint community-academic retrospective mRCC registry to assess
      outcomes. MATERIALS AND METHODS: For this overall survival (OS) analysis, the
      analytic cohort included all patients in the registry diagnosed between January
      1, 2007, to May 31, 2011 (N = 384). Patients were grouped by up to three
      treatment exposures according to each drug's mechanism of action: vascular
      endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI), mammalian target
      of rapamycin inhibitor (mTOR), or no systemic treatment (NSTx, which could
      include radiation or surgery). OS by exposure sequence was evaluated using Kaplan
      Meier, pairwise comparison, and Cox regression analyses. RESULTS: Median OS was
      17.2 months. OS (months) for one exposure was: mTOR 5.4, TKI 18.2, NSTx 18.4; for
      two exposures: mTOR/TKI 9.3, TKI/mTOR 13.9, TKI/TKI 35.2; and for three
      exposures: TKI/mTOR/TKI 20.9, TKI/TKI/mTOR 33.1. By pairwise comparison, OS for
      TKI, mTOR/TKI, TKI/mTOR, TKI/TKI, TKI/mTOR/TKI and TKI/TKI/mTOR sequences was
      greater than mTOR (all P < .04); demographics confirmed that individuals treated
      with early mTOR inhibition more commonly had adverse prognostic features. In Cox
      regression analysis, compared with the referent (TKI), TKI/TKI (hazard ratio =
      0.53; P = .03) had a lower risk of death, and mTOR (hazard ratio = 2.16; P =
      .002) had a higher risk of death. CONCLUSIONS: mRCC survival outcomes are
      different by pattern, with general findings consistent with trial-based
      expectations in similar patient populations. Real-world data can provide context
      around patterns of care and impact when experimental trial data are lacking.

PMID- 24281153
TI  - Prepulse inhibition in HIV-1 gp120 transgenic mice after withdrawal from chronic
      methamphetamine.
AB  - HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both
      factors are associated with impairment in inhibitory function that continues even
      after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure
      of sensorimotor gating, are induced by acute stimulant administration, but the
      combined effect of HIV and chronic METH exposure on PPI is not well
      characterized. We quantified baseline acoustic startle and PPI in mice expressing
      the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates;
      thereafter, we administered a chronic regimen of METH or vehicle and tested
      startle and PPI after 7 days of drug withdrawal. We hypothesized that METH
      treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT
      or gp120tg animals. Before METH administration, drug-naive female gp120tg mice
      exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice
      exhibited increased startle compared with other groups. After drug withdrawal, no
      consistent genotype effect was observed, but METH-treated mice exhibited
      increased PPI compared with vehicle, in contrast to previous reports of acute
      METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on
      factors such as sex, whereas changes in PPI following METH withdrawal may depend
      on the quantity and duration of drug exposure. 

PMID- 24281154
TI  - Genetic complexity in a Drosophila model of diabetes-associated misfolded human
      proinsulin.
AB  - Drosophila melanogaster has been widely used as a model of human Mendelian
      disease, but its value in modeling complex disease has received little attention.
      Fly models of complex disease would enable high-resolution mapping of disease
      modifying loci and the identification of novel targets for therapeutic
      intervention. Here, we describe a fly model of permanent neonatal diabetes
      mellitus and explore the complexity of this model. The approach involves the
      transgenic expression of a misfolded mutant of human preproinsulin, hINS(C96Y),
      which is a cause of permanent neonatal diabetes. When expressed in fly imaginal
      discs, hINS(C96Y) causes a reduction of adult structures, including the eye,
      wing, and notum. Eye imaginal discs exhibit defects in both the structure and the
      arrangement of ommatidia. In the wing, expression of hINS(C96Y) leads to ectopic
      expression of veins and mechano-sensory organs, indicating disruption of wild
      type signaling processes regulating cell fates. These readily measurable
      "disease" phenotypes are sensitive to temperature, gene dose, and sex. Mutant
      (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1
      mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress
      response activation, and produces global change in gene expression. Mutant hINS
      transgene tester strains, when crossed to stocks from the Drosophila Genetic
      Reference Panel, produce F1 adults with a continuous range of disease phenotypes
      and large broad-sense heritability. Surprisingly, the severity of mutant hINS
      induced disease in the eye is not correlated with that in the notum in these
      crosses, nor with eye reduction phenotypes caused by the expression of two
      dominant eye mutants acting in two different eye development pathways, Drop (Dr)
      or Lobe (L), when crossed into the same genetic backgrounds. The tissue
      specificity of genetic variability for mutant hINS-induced disease has,
      therefore, its own distinct signature. The genetic dominance of disease-specific
      phenotypic variability in our model of misfolded human proinsulin makes this
      approach amenable to genome-wide association study in a simple F1 screen of
      natural variation. 

PMID- 24281157
TI  - Stereoselective tandem synthesis of thiazolo fused naphthyridines and
      thienopyridines from o-alkynylaldehydes via Au(III)-catalyzed regioselective 6
      endo-dig ring closure.
AB  - An operationally simple approach for the stereoselective tandem synthesis of
      novel thiazolo fused naphthyridines and thienopyridines by the reaction of o
      alkynylaldehydes with L-cystine methyl ester hydrochloride via Au(III)-catalyzed
      regioselective 6-endo-dig ring closure under mild reaction conditions is
      described. It is noteworthy that alkynes bearing an alkyl and a strong electron
      withdrawing nitro group successfully afforded the desired products in good
      yields.

PMID- 24281156
TI  - Genetic variation for life history sensitivity to seasonal warming in Arabidopsis
      thaliana.
AB  - Climate change has altered life history events in many plant species; however,
      little is known about genetic variation underlying seasonal thermal response. In
      this study, we simulated current and three future warming climates and measured
      flowering time across a globally diverse set of Arabidopsis thaliana accessions.
      We found that increased diurnal and seasonal temperature (1 degrees -3 degrees )
      decreased flowering time in two fall cohorts. The early fall cohort was unique in
      that both rapid cycling and overwintering life history strategies were revealed;
      the proportion of rapid cycling plants increased by 3-7% for each 1 degrees 
      temperature increase. We performed genome-wide association studies (GWAS) to
      identify the underlying genetic basis of thermal sensitivity. GWAS identified
      five main-effect quantitative trait loci (QTL) controlling flowering time and
      another five QTL with thermal sensitivity. Candidate genes include known
      flowering loci; a cochaperone that interacts with heat-shock protein 90; and a
      flowering hormone, gibberellic acid, a biosynthetic enzyme. The identified
      genetic architecture allowed accurate prediction of flowering phenotypes (R(2) >
      0.95) that has application for genomic selection of adaptive genotypes for future
      environments. This work may serve as a reference for breeding and conservation
      genetic studies under changing environments. 

PMID- 24281155
TI  - Effect of genetic variation in a Drosophila model of diabetes-associated
      misfolded human proinsulin.
AB  - The identification and validation of gene-gene interactions is a major challenge
      in human studies. Here, we explore an approach for studying epistasis in humans
      using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression
      of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the
      human disease: it activates conserved stress-response pathways and leads to cell
      death (reduction in eye area). Dominant-acting variants in wild-derived inbred
      lines from the Drosophila Genetics Reference Panel produce a continuous, highly
      heritable distribution of eye-degeneration phenotypes in a hINS(C96Y) background.
      A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp
      peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of
      the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration
      phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in
      the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts,
      also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly
      suggesting a novel link between HS-modified proteins and cellular responses to
      misfolded proteins. Finally, we evaluated allele-specific expression difference
      between the two major sfl-intronic haplotypes in heterozygtes. The results showed
      significant heterogeneity in marker-associated gene expression, thereby leaving
      the causal mutation(s) and its mechanism unidentified. In conclusion, the ability
      to create a model of human genetic disease, map a QTL by GWAS to a specific gene,
      and validate its contribution to disease with available genetic resources and the
      potential to experimentally link the variant to a molecular mechanism demonstrate
      the many advantages Drosophila holds in determining the genetic underpinnings of
      human disease. 

PMID- 24281158
TI  - A case of renal cell carcinoma with inferior vena cava tumor thrombus diagnosed
      during pregnancy.
AB  - Renal cell carcinoma (RCC) during pregnancy is rare, and the treatment of this
      condition requires appropriate steps to treat both the patient and the fetus. To
      the best of our knowledge, this is the first report to describe a case of RCC
      with tumor thrombus in the inferior vena cava (IVC) occurring during pregnancy.
      The affected 46-year-old pregnant woman with placenta previa was clinically
      diagnosed with cT3bN0M0 RCC at 25 weeks gestation. Therapeutic considerations
      included risk of sudden pulmonary embolism, risk of thrombosis or intraoperative
      hemorrhage, and safe delivery of the fetus. After extensive consultation with
      obstetricians and pediatricians, the surgical management was divided into two
      steps. First, the patient underwent Caesarean section and simultaneous
      hysterectomy at 26 weeks gestation. Then, 16 days after delivery, when
      hemodynamics and hemostasis had improved due to termination of gestation, the
      patient underwent radical nephrectomy with concomitant IVC thrombectomy.

PMID- 24281160
TI  - Toward a QFT-based theory of atomic and molecular properties.
AB  - The search for a QED-based (and then QFT-based) formalism that brings solid
      grounds to the whole area of relativistic quantum chemistry was just implicit in
      the first decades of the quantum theory. During the last few years it was shown
      that it is still unclear how to derive a well-defined N-electron relativistic
      Hamiltonian, and also the way negative-energy states may contribute to electron
      correlation. Furthermore, the relationship among electron correlation and
      radiative QED corrections is even more difficult to guess. These are few of the
      fundamental problems that need to be solved before such a program of research is
      finished within the wavefunction approach to quantum physics. The polarization
      propagator formalism was developed as an alternative approach to study atomic and
      molecular properties within both regimes, relativistic and nonrelativistic. In
      this article we expose how far away one can go today working with polarization
      propagators, until including QED (and afterwards QFT) effects. We will uncover
      its deepest formal origin, the path integral formalism, which explains why
      polarization propagators can be written formally the same in both regimes. This
      will also explain why the NR limit is obtained scaling the velocity of light to
      infinity. We shall introduce a few basic aspects of elementary propagators to
      show what they have in common with polarization propagators. Then we shall remark
      on the most important news that appears with the latter ones. Within the
      relativistic regime the contributions of negative energy orbitals to electron
      correlation are straightforwardly included. New insights on the relationship
      between spin and time-reversal operators are also given, together with an ansatz
      on how to consider both, QED and electron correlation effects on the same
      grounds. We focus here on the treatment of NMR spectroscopic parameters within
      such a formalism, that is still not broadly used by the quantum chemistry
      community. Most of the other response properties can be treated in a similar
      manner. 

PMID- 24281159
TI  - The influence of Hispanic ethnicity on parent-provider communication about
      asthma.
AB  - Research has shown that minority caregivers of children with asthma report poorer
      communication with health care providers than nonminority caregivers. Less is
      known about the specific influence of Hispanic ethnicity on parent-provider
      communication. Our objective was to evaluate the influence of Hispanic ethnicity
      on parent-provider communication regarding their child's asthma and on caregiver
      confidence in communicating with their child's provider at a primary care visit.
      Data were obtained from 166 caregivers of children (2-12 years) with persistent
      asthma. Caregiver perceptions of provider communication and confidence were
      evaluated. We found that Hispanic compared to non-Hispanic caregivers reported
      better communication with providers on several items. Hispanic caregivers also
      were more likely to indicate full confidence in their ability to communicate with
      providers. These findings suggest Hispanic caregivers may experience better
      parent-provider communication than non-Hispanics. Further investigation is needed
      to assess provider- and clinic-specific factors that may influence communication
      between minority caregivers and providers.

PMID- 24281161
TI  - The KIT D816V expressed allele burden for diagnosis and disease monitoring of
      systemic mastocytosis.
AB  - The activating KIT D816V mutation plays a central role in the pathogenesis,
      diagnosis, and targeted treatment of systemic mastocytosis (SM). For improved and
      reliable identification of KIT D816V, we have developed an allele-specific
      quantitative real-time PCR (RQ-PCR) with an enhanced sensitivity of 0.01-0.1 %,
      which was superior to denaturing high-performance liquid chromatography (0.5-1 %)
      or conventional sequencing (10-20 %). Overall, KIT D816 mutations were identified
      in 146/147 (99 %) of patients (D816V, n = 142; D816H, n = 2; D816Y, n = 2) with
      SM, including indolent SM (ISM, n = 63, 43 %), smoldering SM (n = 8, 5 %), SM
      with associated hematological non-mast cell lineage disease (SM-AHNMD, n = 16, 11
      %), and aggressive SM/mast cell leukemia +/- AHNMD (ASM/MCL, n = 60, 41 %). If
      positive in BM, the KIT D816V mutation was found in PB of all patients with
      advanced SM (SM-AHNMD, ASM, and MCL) and in 46 % (23/50) of patients with ISM.
      There was a strong correlation between the KIT D816V expressed allele burden (KIT
      D816V EAB) with results obtained from DNA by genomic allele-specific PCR and also
      with disease activity (e.g., serum tryptase level), disease subtype (e.g.,
      indolent vs. advanced SM) and survival. In terms of monitoring of residual
      disease, qualitative and quantitative assessment of KIT D816V and KIT D816V EAB
      was successfully used for sequential analysis after chemotherapy or allogeneic
      stem cell transplantation. We therefore conclude that RQ-PCR assays for KIT D816V
      are useful complimentary tools for diagnosis, disease monitoring, and evaluation
      of prognosis in patients with SM.

PMID- 24281162
TI  - High coating of Ru(II) complexes on gold nanoparticles for single particle
      luminescence imaging in cells.
AB  - Gold nanoparticles are efficiently labelled with a luminescent ruthenium complex,
      producing 13 and 100 nm diameter, monodisperse red-emissive imaging probes with
      luminescence lifetimes prolonged over the molecular unit. Single, 100 nm
      particles are observed in whole cell luminescence imaging which reveals their
      biomolecular association with chromatin in the nucleus of cancer cells. 

PMID- 24281164
TI  - The prognostic value of haplotypes in the vascular endothelial growth factor a
      gene in colorectal cancer.
AB  - New prognostic markers in patients with colorectal cancer (CRC) are a
      prerequisite for individualized treatment. Prognostic importance of single
      nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF
      A) gene has been proposed. The objective of the present study was to investigate
      the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC.
      The study included 486 patients surgically resected for stage II and III CRC,
      divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed
      by polymerase chain reaction. Haplotypes were estimated using the PHASE program.
      The prognostic influence was evaluated using Kaplan-Meir plots and log rank
      tests. Cox regression method was used to analyze the independent prognostic
      importance of different markers. All three SNPs were significantly related to
      survival. A haplotype combination, responsible for this effect, was present in
      approximately 30% of the patients and demonstrated a significant relationship
      with poor survival, and it remained an independent prognostic marker after
      multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49-4.06), p <
      0.001. Validation was provided by consistent findings in a second and independent
      cohort. Haplotype combinations call for further investigation. 

PMID- 24281163
TI  - The changing face of esophageal cancer.
AB  - The two main histological esophageal cancer types, adenocarcinoma and squamous
      cell carcinoma, differ in incidence, geographic distribution, ethnic pattern and
      etiology. This article focuses on epidemiology with particular reference to
      geographic and temporal variations in incidence, along with a review of the
      evidence supporting environmental and genetic factors involved in esophageal
      carcinogenesis. Squamous cell carcinoma of the esophagus remains predominantly a
      disease of the developing world. In contrast, esophageal adenocarcinoma is mainly
      a disease of western developed societies, associated with obesity and gastro
      esophageal reflux disease. There has been a dramatic increase in the incidence of
      adenocarcinoma in developed countries in parallel with migration of both
      esophageal and gastric adenocarcinomas towards the gastro-esophageal junction. 

PMID- 24281165
TI  - The problems of radiofrequency ablation as an approach for advanced unresectable
      ductal pancreatic carcinoma.
AB  - Advanced ductal pancreatic carcinoma (PC) remains a challenge for current
      surgical and medical approaches. It has recently been claimed that radiofrequency
      ablation (RFA) may be beneficial for patients with locally advanced or metastatic
      PC. Using the MEDLINE database, we found seven studies involving 106 patients in
      which PC was treated using RFA. The PC was mainly located in the pancreatic head
      (66.9%) with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1%)
      with locally advanced PC and in 21 (19.9%) with metastatic disease. Palliative
      surgical procedures were carried out in 41.5% of the patients. The average
      temperature used was 90  degrees C (with a temperature range of 30-105  degrees
      C) and the ratio between the number of passes of the probe and the size of the
      tumor in centimeters was 0.5 (range of 0.36-1). The median postoperative
      morbidity and mortality were 28.3% and 7.5%, respectively; the median survival
      was 6.5 months (range of 1-33 months). In conclusion, RFA is a feasible
      technique: however, its safety and long-term results are disappointing; Thus, the
      RFA procedure should not be recommended in clinical practice for a PC patient. 

PMID- 24281166
TI  - PCA3 and TMPRSS2-ERG: Promising Biomarkers in Prostate Cancer Diagnosis.
AB  - The search for the biomarkers to precisely and non-invasively characterize the
      biology of prostate cancer (PCa) is the focus of many laboratories across the
      world. Although prostate-specific antigen (PSA) remains the standard diagnostic
      tool for PCa, its low specificity leads to unnecessary biopsies in a substantial
      number of patients. More importantly, with the current status of knowledge, it is
      very difficult to early identify individuals with a life-threatening disease who
      require an immediate treatment. The significant advances in genetics and
      biotechnology in recent years has led to the discovery of new molecular markers
      including PCA3 and the TMPRSS2:ERG genomic fusion. Both PCA3 and TMPRSS2:ERG,
      compared to PSA, show an increased specificity in PCa detection. However, the
      quest for a single PCa marker that can fully satisfy urologists and their
      patients is still ongoing. The aim of this review is to present the recent
      findings on PCA3 and TMPRSS2:ERG and to describe their clinical implications and
      performance. 

PMID- 24281167
TI  - Models of hepatocellular carcinoma and biomarker strategy.
AB  - The overwhelming need to improve preclinical models in oncology has stimulated
      research efforts to refine and validate robust orthotopic models that closely
      mimic the disease population and therefore have the potential to better predict
      clinical outcome with novel therapies. Sophisticated technologies including
      bioluminescence, contrast enhanced ultrasound imaging, positron emission
      tomography, computed tomography and magnetic resonance imaging have been added to
      existing serum- and histology-based biomarkers to assist with patient selection
      and the design of clinical trials. The rationale for the use of human
      hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and
      orthotopic animal models and utilization of available biomarkers have been
      discussed, providing guidelines to facilitate preclinical research for the
      development of treatments for HCC patients. 

PMID- 24281169
TI  - The Kinase Mirk/dyrk1B: A Possible Therapeutic Target in Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinomas are strongly resistant to chemotherapeutic
      drugs and radiation, underscoring the need for new therapeutic targets,
      particularly ones which target the numerous out of cycle cancer cells. Analysis
      of resected tumors for nuclear Ki67 antigen has shown that about 70% of
      pancreatic cancer cells are out of cycle, some post-mitotic. Other out of cycle
      cells are in a quiescent, reversible G0 state, resistant to drugs which target
      dividing cells, with some able to repopulate a tumor. The serine/threonine kinase
      Mirk/dyrk1B is a downstream effector of oncogenic K-ras, the most common mutation
      in this cancer. Mirk expression is elevated in quiescent pancreatic cancer cells
      and mediates their prolonged survival through increasing expression of a cohort
      of antioxidant genes. Mirk is expressed in about 90% of pancreatic cancers and is
      amplified in a subset. Mirk appears not to be an essential gene for normal cells
      from embryonic knockout studies in mice and RNA interference studies on cultured
      cells, but is upregulated in pancreatic tumor cells. These unusual
      characteristics suggest that Mirk may be a selective target for therapeutic
      intervention. 

PMID- 24281170
TI  - Neural invasion in pancreatic cancer: the past, present and future.
AB  - In the past 15 years, invasion of nerves by cancer cells has escaped from its
      role as a mere bystander in cancer biology and turned into an attractive niche to
      study the heterotypic interaction between cancer cells and neurons. Today, neural
      invasion (NI) in pancreatic cancer (PCa) stands out due to the recent
      demonstration of its association with tumor progression, local recurrence and
      neuropathic pain. Accordingly, recent research on NI in PCa revealed the critical
      involvement of numerous nerve- or cancer cell-derived molecules in several novel
      in vitro and in vivo models of NI, which, however, still need further major
      improvement. 

PMID- 24281168
TI  - YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in
      Cancer Patients?
AB  - YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and
      stem cells. It probably has a role in cell proliferation and differentiation,
      inflammation, protection against apoptosis, stimulation of angiogenesis, and
      regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often
      elevated in patients with localized or advanced cancer compared to age-matched
      healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an
      independent prognostic biomarker of short survival in patients with different
      types of cancer. However, there is not yet sufficient data to support
      determination of plasma YKL-40 outside research projects as a biomarker for
      screening of gastrointestinal cancer and determination of treatment response and
      poor prognosis before or during treatment and follow-up. Plasma YKL-40 is also
      elevated in patients with other diseases than cancer, e.g., severe infections,
      cardiovascular disease, diabetes, chronic obstructive lung disease, asthma, liver
      fibrosis and rheumatoid arthritis. Co-morbidity should therefore always be
      considered in patients with cancer, since other sources than cancer cells can
      increase plasma YKL-40 levels. Future focused translational research projects
      combining basic and clinical research are needed in a joint effort to answer
      questions of the complex function and regulation of YKL-40 and the question if
      plasma YKL-40 is a clinical useful biomarker in patients with cancer. 

PMID- 24281171
TI  - A quest for initiating cells of head and neck cancer and their treatment.
AB  - The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers
      have been related to cancer stem-like cells (CSC). Specific markers, which vary
      considerably depending on tumor type or tissue of origin, characterize CSC. CSC
      are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors,
      CSC are less sensitive to chemo- and radiotherapy and may have low
      immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC
      has two main etiologies: human papillomavirus, a virus infecting epithelial stem
      cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC
      biology is reviewed and parallels to CSC of other origin are drawn where
      necessary for a comprehensive picture. 

PMID- 24281172
TI  - The Role of Macrophage Migration Inhibitory Factor (MIF) in Ultraviolet Radiation
      Induced Carcinogenesis.
AB  - Ultraviolet (UV) radiation is the most common cause of physical injury to the
      skin due to environmental damage, and UV exposure substantially increases the
      risk of actinic damage to the skin. The inflammatory changes induced by acute UV
      exposure include erythema (sunburn) of the skin, while chronic exposure to solar
      UV radiation causes photo-aging, immunosuppression, and ultimately,
      carcinogenesis of the skin. After skin damage by UV radiation, the cells are
      known to secrete many cytokines, including interleukin (IL)-1, IL-6, tumor
      necrosis factor (TNF)-alpha. and macrophage migration inhibitory factor (MIF).
      MIF was originally identified as a lymphokine that concentrates macrophages at
      inflammatory loci, and is known to be a potent activator of macrophages in vivo.
      MIF is considered to play an important role in cell-mediated immunity. Since the
      molecular cloning of MIF cDNA, MIF has been re-evaluated as a proinflammatory
      cytokine and pituitary-derived hormone that potentiates endotoxemia. MIF is
      ubiquitously expressed in various tissues, including the skin. Recent studies
      have suggested a potentially broader role for MIF in growth regulation because of
      its ability to antagonize p53-mediated gene activation and apoptosis. This
      article reviews the latest findings on the roles of MIF with regard to UV-induced
      skin cancer. 

PMID- 24281173
TI  - Stereotactic Body Radiation Therapy (SBRT) for Unresectable Pancreatic Carcinoma.
AB  - Survival in patients with unresectable pancreatic carcinoma is poor. Studies by
      Mayo Clinic and the Gastrointestinal Tumor Study Group (GITSG) have established
      combined modality treatment with chemotherapy and radiation as the standard of
      care. Use of gemcitabine-based chemotherapy alone has also been shown to provide
      a benefit, but 5-year overall survival still remains less than 5%. Conventional
      radiotherapy is traditionally delivered over a six week period and high toxicity
      is seen with the concomitant use of chemotherapy. In contrast, SBRT can be
      delivered in 3-5 days and, when used as a component of combined modality therapy
      with gemcitabine, disruption to the timely delivery of chemotherapy is minimal.
      Early single-institution reports of SBRT for unresectable pancreatic carcinoma
      demonstrate excellent local control with acceptable toxicity. Use of SBRT in
      unresectable pancreatic carcinoma warrants further investigation in order to
      improve the survival of patients with historically poor outcomes. 

PMID- 24281175
TI  - Dermoscopy of scalp melanoma: report of three cases.
AB  - Scalp melanoma is rare and often late-discovered because of its unusual position.
      As a consequence, its prognosis is poorer than melanoma on other body sites and
      only few clinical reports about its dermoscopic pattern have been published. In
      this paper, we report three clinical cases of scalp melanoma with photographic
      documentation and dermoscopic images, in order to improve the early detection of
      scalp melanoma. 

PMID- 24281174
TI  - The emerging role of the phosphatidylinositol 3-kinase/ akt/mammalian target of
      rapamycin signaling network in cancer stem cell biology.
AB  - The cancer stem cell theory entails the existence of a hierarchically organized,
      rare population of cells which are responsible for tumor initiation, self
      renewal/maintenance, and mutation accumulation. The cancer stem cell proposition
      could explain the high frequency of cancer relapse and resistance to currently
      available therapies. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian
      target of rapamycin (mTOR) signaling pathway regulates a wide array of
      physiological cell functions which include differentiation, proliferation,
      survival, metabolism, autophagy, and motility. Dysregulated PI3K/Akt/mTOR
      signaling has been documented in many types of neoplasias. It is now emerging
      that this signaling network plays a key role in cancer stem cell biology.
      Interestingly, cancer stem cells displayed preferential sensitivity to pathway
      inhibition when compared to healthy stem cells. This observation provides the
      proof-of-principle that functional differences in signaling pathways between
      neoplastic stem cells and healthy stem cells could be identified. In this review,
      we present the evidence which links the signals emanating from the PI3K/Akt/mTOR
      cascade with the functions of cancer stem cells, both in solid and hematological
      tumors. We then highlight how targeting PI3K/Akt/mTOR signaling with small
      molecules could improve cancer patient outcome. 

PMID- 24281176
TI  - Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic
      Approach Based on Time-of-Flight Mass Spectrometry.
AB  - Biliary tract cancers (BTCs) are lethal malignancies currently lacking
      satisfactory methods for early detection and accurate diagnosis. Surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a
      promising diagnostic tool for this disease. In this pilot study, sera samples
      from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a
      population-based case-control study were randomly grouped into training set (30
      BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind
      set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on
      Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree
      classifier was built using the training set and applied to all test sets. The
      classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242
      mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a
      specificity of 85.0% when comparing BTCs with non-cancers. When applied to the
      duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the
      blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive
      values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%,
      respectively. The agreement of the training and duplicate sets was 71.4% (Kappa =
      0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates
      of one sample for the five differential peaks were 15.8-68.8% for intensity and 0
      0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI
      TOF-MS may be a promising approach for identifying BTCs but low assay
      reproducibility may limit its application in clinical practice. 

PMID- 24281177
TI  - ZEB1 in Pancreatic Cancer.
AB  - Pancreatic cancer is one of the most malignant human neoplasias. On the molecular
      level, epithelial-mesenchymal transition (EMT) has been demonstrated to
      contribute to the malignant phenotype of pancreatic cancer cells. ZEB1 is a
      transcriptional repressor that has been identified as an inducer of EMT. A
      negative feedback loop between ZEB1 and microRNA-200c has been shown to regulate
      this EMT induction in various models. With respect to pancreatic cancer, primary
      effects of EMT comprise increased local and distant tumor cell dissemination.
      Another recently described feature of the EMT is the acquisition of cancer stem
      cell traits. For pancreatic cancer cells, antagonism between ZEB1 and stemness
      inhibiting micro-RNAs has been demonstrated to contribute to this process,
      providing experimental support for the migrating cancer stem cell (MCSC)
      hypothesis. ZEB1 has also been shown to be associated with drug resistance of
      pancreatic cancer cells. This article reviews the biological functions of ZEB1
      with a focus on pancreatic cancer. 

PMID- 24281178
TI  - Cancer stem cells in pancreatic cancer.
AB  - Pancreatic cancer is an aggressive malignant solid tumor well-known by early
      metastasis, local invasion, resistance to standard chemo- and radiotherapy and
      poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated
      and propagated by cancer stem cells (CSCs). Here we review the current research
      results regarding CSCs in pancreatic cancer and discuss the different markers
      identifying pancreatic CSCs. This review will focus on metastasis, microRNA
      regulation and anti-CSC therapy in pancreatic cancer. 

PMID- 24281179
TI  - The Clinical Significance of Unknown Sequence Variants in BRCA Genes.
AB  - Germline mutations in BRCA1/2 genes are responsible for a large proportion of
      hereditary breast and/or ovarian cancers. Many highly penetrant predisposition
      alleles have been identified and include frameshift or nonsense mutations that
      lead to the translation of a truncated protein. Other alleles contain missense
      mutations, which result in amino acid substitution and intronic variants with
      splicing effect. The discovery of variants of uncertain/unclassified significance
      (VUS) is a result that can complicate rather than improve the risk assessment
      process. VUSs are mainly missense mutations, but also include a number of
      intronic variants and in-frame deletions and insertions. Over 2,000 unique BRCA1
      and BRCA2 missense variants have been identified, located throughout the whole
      gene (Breast Cancer Information Core Database (BIC database)). Up to 10-20% of
      the BRCA tests report the identification of a variant of uncertain significance.
      There are many methods to discriminate deleterious/high-risk from neutral/low
      risk unclassified variants (i.e., analysis of the cosegregation in families of
      the VUS, measure of the influence of the VUSs on the wild-type protein activity,
      comparison of sequence conservation across multiple species), but only an
      integrated analysis of these methods can contribute to a real interpretation of
      the functional and clinical role of the discussed variants. The aim of our
      manuscript is to review the studies on BRCA VUS in order to clarify their
      clinical relevance. 

PMID- 24281181
TI  - Epigenetic therapy in human choriocarcinoma.
AB  - Because epigenetic alterations are believed to be involved in the repression of
      tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel
      compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an
      attractive therapeutic approach. HDAC inhibitors (HDACIs) were able to mediate
      inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of
      genes related to the malignant phenotype in choriocarcinoma cell lines. In this
      review, we discuss the biologic and therapeutic effects of HDACIs in treating
      choriocarcinoma, with a special focus on preclinical studies. 

PMID- 24281180
TI  - Interaction of stellate cells with pancreatic carcinoma cells.
AB  - Pancreatic cancer is characterized by its late detection, aggressive growth,
      intense infiltration into adjacent tissue, early metastasis, resistance to chemo-
      and radiotherapy and a strong "desmoplastic reaction". The dense stroma
      surrounding carcinoma cells is composed of fibroblasts, activated stellate cells
      (myofibroblast-like cells), various inflammatory cells, proliferating vascular
      structures, collagens and fibronectin. In particular the cellular components of
      the stroma produce the tumor microenvironment, which plays a critical role in
      tumor growth, invasion, spreading, metastasis, angiogenesis, inhibition of
      anoikis, and chemoresistance. Fibroblasts, myofibroblasts and activated stellate
      cells produce the extracellular matrix components and are thought to interact
      actively with tumor cells, thereby promoting cancer progression. In this review,
      we discuss our current understanding of the role of pancreatic stellate cells
      (PSC) in the desmoplastic response of pancreas cancer and the effects of PSC on
      tumor progression, metastasis and drug resistance. Finally we present some novel
      ideas for tumor therapy by interfering with the cancer cell-host interaction. 

PMID- 24281182
TI  - DLEC1 Expression Is Modulated by Epigenetic Modifications in Hepatocelluar
      Carcinoma Cells: Role of HBx Genotypes.
AB  - Deleted in Lung and Esophageal Cancer 1 (DLEC1) is a functional tumor suppressor
      gene (TSG). It has been found to be silenced in a variety of human cancers
      including hepatocellular carcinoma (HCC). The silencing of DLEC1 can be modulated
      by epigenetic modifications, such as DNA hypermethylation and histone
      hypoacetylation. In the case of HCC, hepatitis B virus X protein (HBx) has been
      implicated in methylation of target promoters resulting in the down-regulation of
      tumor suppressor genes, which in turn contributes to the development of HCC. In
      the present study, we first established a cell system in which epigenetic
      modifications can be modulated using inhibitors of either DNA methylation or
      histone deacetylation. The cell system was used to reveal that the expression of
      DLEC1 was upregulated by HBx in a genotype-dependent manner. In particular, HBx
      genotype A was found to decrease DNA methylation of the DLEC1 promoter. Our
      results have provided new insights on the impact of HBx in HCC development by
      epigenetic modifications. 

PMID- 24281183
TI  - Aberrant crypt foci: the case for inclusion as a biomarker for colon cancer.
AB  - Aberrant crypt foci (ACF) are one of the earliest histopathological
      manifestations of colon cancer. In this review, we critically present the
      molecular, cellular, histopathological, and chemopreventive evidence that ACF are
      relevant biomarkers for colon cancer. The laboratory and clinical evidence are
      highly suggestive that ACF are in the pathway leading to colon cancer, but not
      all ACF will do so. The possible fate and outcome of ACF in the progression
      toward colon cancer may be dependent on a number of features that define their
      predictive power for the prevention or progression of cancer. 

PMID- 24281184
TI  - 5-fu metabolism in cancer and orally-administrable 5-fu drugs.
AB  - 5-Fluorouracil (5-FU) is a key anticancer drug that for its broad antitumor
      activity, as well as for its synergism with other anticancer drugs, has been used
      to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has
      been combined with oxaliplatin, irinotecan and other drugs as a continuous
      intravenous infusion. Recent clinical chemotherapy studies have shown that
      several of the regimens with oral 5-FU drugs are not inferior compared to those
      involving continuous 5-FU infusion chemotherapy, and it is probable that in some
      regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs.
      Historically, both the pharmaceutical industry and academia in Japan have been
      involved in the development of oral 5-FU drugs, and this review will focus on the
      current knowledge of 5-FU anabolism and catabolism, and the available information
      about the various orally-administrable 5-FU drugs, including UFT, S-1 and
      capecitabine. Clinical studies comparing the efficacy and adverse events of S-1
      and capecitabine have been reported, and the accumulated results should be
      utilized to optimize the treatment of cancer patients. On the other hand, it is
      essential to elucidate the pharmacokinetic mechanism of each of the newly
      developed drugs, to correctly select the drugs for each patient in the clinical
      setting, and to further develop optimized drug derivatives. 

PMID- 24281186
TI  - Enzyme-modified Panax ginseng inhibits UVB-induced skin aging through the
      regulation of procollagen type I and MMP-1 expression.
AB  - Panax ginseng Meyer (Ginseng) has been used widely in traditional herbal medicine
      because of its pharmacological activities. In this study, we tested the ability
      of an enzyme-modified ginseng extract (EG) to protect the skin against
      ultraviolet B (UVB)-induced damage using cultured human dermal fibroblasts and
      hairless mice. EG, an extract which is rich in the active compound ginsenoside
      F2, and purified ginsenoside F2 were used in these experiments. The ginsenoside
      content of EG was measured by liquid chromatography-mass spectrometry (LC-MS).
      The potential of EG to reduce UVB-induced skin damage was investigated by
      determining the levels of procollagen type I and metalloproteinase-1 (MMP-1)
      after UVB irradiation in human dermal fibroblasts and by examining the levels of
      hydration, thickness, and density of collagen fibers in the UVB-exposed dorsal
      skin of hairless mice. LC-MS analysis detected a difference in the ginsenoside
      content between normal white ginseng and enzyme-modified ginseng. In UVB
      irradiated human dermal fibroblasts treated with EG, MMP-1 production
      considerably decreased without cell toxicity. Furthermore, topical application of
      EG showed significant reductions in skin dryness, thickness, and fragmented
      collagen fibers in UVB-exposed hairless mice. Ginsenoside F2, an active component
      of EG, increased procollagen type I production and decreased MMP-1 secretion in
      UV-irradiated human dermal fibroblasts. EG and ginsenoside F2 are potentially
      useful for the prevention and treatment of UVB-induced skin damage. 

PMID- 24281187
TI  - Reply to the comments by Andreas Charidimou and David J. Werring.

PMID- 24281185
TI  - Bioelectric applications for treatment of melanoma.
AB  - Two new cancer therapies apply bioelectric principles. These methods target tumor
      structures locally and function by applying millisecond electric fields to
      deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by
      applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been
      used to locally deliver cytokines such as IL-12 to activate an immune response,
      resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and
      affect vascular networks, both promoting tumor demise and restoration of normal
      vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs
      are used in models with B16F10 melanoma in vitro and in mice. Applications of
      bioelectrics, using conventional electroporation and extensions of it, provide
      effective alternative therapies for melanoma. 

PMID- 24281188
TI  - Effect of Preoperative Brace Treatment on the Mental Health Scores of SRS-22 and
      SF-36 Questionnaire in Surgically Treated Adolescent Idiopathic Scoliosis
      Patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: The aim of this study was to
      analyze whether there were differences in mental health scores of Scoliosis
      Research Society-22 (SRS-22) questionnaire and Short Form-36 (SF-36)
      questionnaire between adolescent idiopathic scoliosis (AIS) patients with/without
      preoperative brace treatment. SUMMARY OF BACKGROUND DATA: Mental health is an
      important domain of SRS-22 and SF-36 questionnaire. There are few studies focused
      on the effect of preoperative brace treatment on mental health in surgically
      treated AIS patients. MATERIALS AND METHODS: The SRS-22 and SF-36 questionnaires
      of 211 AIS patients who underwent posterior correction surgery were
      retrospectively reviewed. The average age of the patients was 14.4 years (range,
      11-18 y), and the patients were classified into 2 groups: with preoperative brace
      treatment (group BS-32 cases, 5 male and 27 female) and without preoperative
      brace treatment (group S-179 cases, 23 male and 156 female). The radiographic
      data and mental health scores of SRS-22 and SF-36 questionnaires were compared
      between the 2 groups. RESULTS: There was no significant difference in terms of
      height, rib hump, the mean preoperative coronal Cobb angle or apical vertebral
      translation of the major curve, sagittal thoracic kyphosis, or coronal trunk
      balance between group BS and group S (all P>0.05). The average and total mental
      health scores of SRS-22 between group BS and group S were 3.6+/-0.7 and 3.7+/
      0.5, and 18.1+/-3.5 and 18.3+/-2.6, respectively. The total mental health scores
      of SF-36 between group BS and group S were 71.1+/-8.7 and 68.7+/-11.5,
      respectively. There was no significant difference with regard to the mental
      health scores of SRS-22 and SF-36 questionnaires between group BS and group S
      (all P>0.05). CONCLUSIONS: Preoperative brace treatment did not have obvious
      influence on the mental health scores of SRS-22 and SF-36 questionnaires in
      surgically treated AIS patients.

PMID- 24281190
TI  - Metabolism: Young again with Lin28.

PMID- 24281191
TI  - Chromosomes: now in 3D!

PMID- 24281189
TI  - Activation of NAD(P)H oxidase by tryptophan-derived 3-hydroxykynurenine
      accelerates endothelial apoptosis and dysfunction in vivo.
AB  - RATIONALE: The kynurenine (Kyn) pathway is the major route for tryptophan (Trp)
      metabolism in mammals. The Trp-Kyn pathway is reported to regulate several
      fundamental biological processes, including cell death. OBJECTIVE: The aim of
      this study was to elucidate the contributions and molecular mechanism of Trp-Kyn
      pathway to endothelial cell death. METHODS AND RESULTS: Endogenous reactive
      oxygen species, endothelial cell apoptosis, and endothelium-dependent and
      endothelium-independent vasorelaxation were measured in aortas of wild-type mice
      or mice deficient for nicotinamide adenine dinucleotide phosphate [NAD(P)H]
      oxidase subunits (p47(phox) or gp91(phox)) or indoleamine-pyrrole 2,3-dioxygenase
      1 with or without angiotensin (Ang) II infusion. As expected, AngII increased
      plasma levels of Kyn- and 3-hydroxykynurenine-modified proteins in endothelial
      cells in vivo. Consistent with this, AngII markedly increased the expression of
      indoleamine-pyrrole 2,3-dioxygenase in parallel with increased expression of
      interferon-gamma. Furthermore, in wild-type mice, AngII significantly increased
      oxidative stress, endothelial cell apoptosis, and endothelial dysfunction. These
      effects of AngII infusion were significantly suppressed in mice deficient for
      p47(phox), gp91(phox), or indoleamine-pyrrole 2,3-dioxygenase 1, suggesting that
      AngII-induced enhancement of Kynurenines via NAD(P)H oxidase-derived oxidants
      causes endothelial cell apoptosis and dysfunction in vivo. Furthermore,
      interferon-gamma neutralization eliminates AngII-increased superoxide products
      and endothelial apoptosis by inhibiting AngII-induced Kynurenines generation,
      suggesting that AngII-activated Kyn pathway is interferon-gamma-dependent.
      Mechanistically, we found that AngII-enhanced 3-hydroxykynurenine promoted the
      generation of NAD(P)H oxidase-mediated superoxide anions by increasing the
      translocation and membrane assembly of NAD(P)H oxidase subunits in endothelial
      cells, resulting in accelerated apoptosis and consequent endothelial dysfunction.
      CONCLUSIONS: Kyn pathway activation accelerates apoptosis and dysfunction of the
      endothelium by upregulating NAD(P)H-derived superoxide.

PMID- 24281192
TI  - RNA metabolism: The CBC social network.

PMID- 24281193
TI  - Pharyngeal cancer surveillance using narrow band imaging during conventional
      upper gastrointestinal endoscopy.
AB  - BACKGROUND: Recent studies have suggested that narrow band imaging (NBI) is
      useful for detecting superficial pharyngeal cancer. Nevertheless, pharyngeal
      observation is not a routine practice during upper gastrointestinal (GI)
      endoscopy. Two aims of this study were to evaluate the feasibility of pharyngeal
      observation during upper GI endoscopy and to determine the prevalence of
      pharyngeal cancer in asymptomatic high-risk patients. METHODS: Fifty-year-old or
      older asymptomatic males with smoking and drinking habits were prospectively
      recruited as a pharyngeal cancer high-risk group. A total of 224 high-risk
      patients underwent pharyngeal observation using NBI before conventional upper GI
      endoscopy. The feasibility of pharyngeal examination without sedation was
      assessed by a questionnaire for the first 60 participants. RESULTS: The median
      time for pharyngeal observation was 1.7 min. The questionnaire demonstrated 88%
      of participants thought the pharyngeal examination acceptable. The NBI
      examination identified 5 superficial pharyngeal cancers (2 Tis and 3 T1) in 224
      high-risk patients; the prevalence of pharyngeal cancer in this group was 2.2%.
      Three of the 5 patients had a concurrent or past history of esophageal squamous
      cell carcinoma (ESCC). CONCLUSIONS: Pharyngeal observation using NBI during upper
      GI endoscopy is well tolerated and recommended for all high-risk patients,
      particularly those with a history of ESCC. Basel.

PMID- 24281194
TI  - Diastereoselective synthesis of epoxide-fused benzoquinolizidine derivatives
      using intramolecular domino aza-Michael addition/Darzens reaction.
AB  - An efficient and diastereoselective strategy based on an intramolecular domino
      aza-Michael/Darzens reaction to synthesize epoxide-fused benzoquinolizidines has
      been described. Three bonds (1 C-C, 1 C-N and 1 C-O), three rings and three
      chiral centers can be constructed in a single pot under very mild conditions. All
      the products were isolated in only one diastereomer with 40-80% yields. 

PMID- 24281195
TI  - Continents divided: Understanding differences between Europe and North America in
      acceptance of GM crops.
AB  - The differences between GM policies in the US and Europe have several causes. GM
      technology holds a home court advantage in the US and European chemical companies
      did not support its introduction. The technology did not seem to provide benefits
      to consumers, and the crops it applied to were not so significant in Europe. The
      technology was introduced during a time when the political influence of green
      parties in Europe was especially significant, and European trust of government
      capacity to enter food security issues was at its lowest. 

PMID- 24281196
TI  - Another look at outcomes and outcome measures in psychiatry: cui bono?

PMID- 24281197
TI  - TS mRNA levels can predict pemetrexed and raltitrexed sensitivity in colorectal
      cancer.
AB  - PURPOSE: The purpose of the study is to analyze the relationship between tumor
      thymidylate synthase (TS) mRNA expression levels and raltitrexed/pemetrexed/5-FU
      sensitivity. PATIENTS AND METHODS: We collected freshly removed colorectal tumor
      specimens from 50 patients. Chemosensitivities to anticancer drugs were evaluated
      by histoculture drug response assay. We adopted quantitative reverse
      transcription polymerase chain reaction for TS mRNA detection and
      immunohistochemical staining for assessing TS expression in tumor tissues.
      RESULTS: There is a significant relationship between TS mRNA expression levels
      and in vitro chemosensitivity of freshly removed colorectal tumor specimens to
      pemetrexed (P < 0.001)/raltitrexed (P = 0.004)/5-FU (P = 0.007). CONCLUSIONS: TS
      mRNA expression levels can predict pemetrexed and raltitrexed sensitivity in
      colorectal cancer.

PMID- 24281198
TI  - Distal phalangeal necrosis in the extremities as a paraneoplastic syndrome in
      prostate cancer: an extremely rare case.
AB  - Paraneoplastic syndromes (PNSs) are rare disorders which are triggered by an
      altered immune system response to a neoplasm. Although prostate cancer (PCa) is
      the second most common urological malignancy associated with PNSs, literature is
      lacking in defining the cases representing different PNSs in PCa. Herein, we
      present a 50-year-old man with fulminant distal phalangeal necrosis in the lower
      extremities after a diagnosis of PCa. Additionally, we review the literature in
      light of this case.

PMID- 24281199
TI  - Oxygen adsorption on single layer graphyne: a DFT study.
AB  - Graphyne is a rising two-dimensional (2D) carbon allotrope with excellent
      electronic properties. In this paper, theoretical calculations were performed to
      study the corresponding electronic properties of the oxygenated graphyne. Atomic
      oxygen when bound to the carbon atom of graphyne forms a stable oxide, with a
      much larger binding energy compared to that on graphene. Owing to the oxygen
      adsorption, the alpha- and beta-graphyne change from a zero-band-gap material to
      a semiconductor as indicated in the band structure calculations. Moreover, spin
      splitting was observed from the band structure of the oxygenated gamma-graphyne.
      These electronic properties are tunable by altering the oxygen coverage through
      changing the supercell size. Our results based on the first-principles
      calculations imply that oxygenation is a promising method to functionalize
      graphyne to achieve designated properties. 

PMID- 24281200
TI  - Breast cancer: surgery at the South egypt cancer institute.
AB  - Breast cancer is the most frequent malignant tumor in women worldwide. In Egypt,
      it is the most common cancer among women, representing 18.9% of total cancer
      cases (35.1% in women and 2.2% in men) among the Egypt National Cancer
      Institute's (NCI) series of 10,556 patients during the year 2001, with an age
      adjusted rate of 49.6 per 100,000 people. In this study, the data of all breast
      cancer patients presented to the surgical department of the South Egypt cancer
      Institute (SECI) hospital during the period from Janurary 2001 to December 2008
      were reviewed .We report the progress of the availability of breast cancer
      management and evaluation of the quality of care delivered to breast cancer
      patients. The total number of patients with a breast lump presented to the SECI
      during the study period was 1,463 patients (32 males and 1431 females); 616
      patients from the total number were admitted at the surgical department .There
      was a decline in advanced cases. Since 2001, facilities for all lines of
      comprehensive management have been made accessible for all patients. We found
      that better management could lead to earlier presentation, and better overall
      outcome in breast cancer patients.The incidence is steadily increasing with a
      tendency for breast cancer to occur in younger age groups and with advanced
      stages. 

PMID- 24281202
TI  - Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis.
AB  - Recent lung cancer studies have focused on identifying the effects of single
      nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes
      are increasingly being studied. Genetic variations in DNA repair genes are
      thought to modulate DNA repair capacity and are suggested to be related to lung
      cancer risk. In this study, we tried to assess reported studies of association
      between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys
      and lung cancer. We conducted MEDLINE, Current Contents and Web of Science
      searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search
      for papers published (from January 1995 through August 2010). Data were combined
      using both a fixed effects (the inverse variance-weighted method) and a random
      effects (DerSimonian and Laird method) model. The Cochran Q test was used for the
      assessment of heterogeneity. Publication bias was assessed by both Begg's and
      Egger's tests. We identified 20 case-control studies in 21 different ethnic
      populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case
      control studies in 19 different ethnic populations (7,792 cases and 9,358
      controls) were included in our meta-analysis. Summary frequencies of the Cys
      allele among aucasians and Asians based on the random effects model were 20.9%
      (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0),
      respectively. The distribution of the Cys allele was significantly different
      between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly
      associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI
      = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung
      cancer risk may be due to environmental factors such as cigarette smoking and
      dietary factors. Although the summary risk for developing lung cancer may not be
      large, lung cancer is such a common malignancy that even a small increase in risk
      can translate to a large number of excess lung cancer cases. As lung cancer is a
      multifactorial disease, further investigations of the gene-gene and gene
      environment interactions on the hOGG1 polymorphism-associated lung cancer risk
      may help to better understand of the molecular pathogenesis of human lung cancer.

PMID- 24281201
TI  - Mucins and pancreatic cancer.
AB  - Pancreatic cancer is characterized by an often dramatic outcome (five year
      survival < 5%) related to a late diagnosis and a lack of efficient therapy.
      Therefore, clinicians desperately need new biomarkers and new therapeutic tools
      to develop new efficient therapies. Mucins belong to an ever increasing family of
      O-glycoproteins. Secreted mucins are the main component of mucus protecting the
      epithelia whereas membrane-bound mucins are thought to play important biological
      roles in cell-cell and cell-matrix interactions, in cell signaling and in
      modulating biological properties of cancer cells. In this review, we will focus
      on the altered expression pattern of mucins in pancreatic cancer, from the early
      neoplastic lesion Pancreatic Intraepithelial Neoplasia (PanIN) to invasive
      pancreatic carcinomas, and the molecular mechanisms (including genetic and
      epigenetic regulation) and signaling pathways known to control their expression.
      Moreover, we will discuss the recent advances about the biology of both secreted
      and membrane-bound mucins and their key roles in pancreatic carcinogenesis and
      resistance to therapy. Finally, we will discuss exciting opportunities that
      mucins offer as potential therapeutic targets in pancreatic cancer. 

PMID- 24281203
TI  - Pancreatic cancer biomarkers and their implication in cancer diagnosis and
      epidemiology.
AB  - Pancreatic cancer is the fourth most common cause of cancer-related mortality in
      the United States. Biomarkers are needed to detect this cancer early during the
      disease development and for screening populations to identify those who are at
      risk. In cancer, "biomarker" refers to a substance or process that is indicative
      of the presence of cancer in the body. A biomarker might be either a molecule
      secreted by a tumor or it can be a specific response of the body to the presence
      of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can
      be used for cancer diagnosis, prognosis, and epidemiology. A number of potential
      biomarkers have been identified for pancreatic cancer. These markers can be
      assayed in non-invasively collected biofluids. These biomarkers need analytical
      and clinical validation so that they can be used for the purpose of screening and
      diagnosing pancreatic cancer and determining disease prognosis. In this article,
      the latest developments in pancreatic cancer biomarkers are discussed. 

PMID- 24281205
TI  - Familial pancreatic cancer.
AB  - Pancreatic cancer's high mortality rate equates closely with its incidence,
      thereby showing the need for development of biomarkers of its increased risk and
      a better understanding of its genetics, so that high-risk patients can be better
      targeted for screening and early potential lifesaving diagnosis. Its phenotypic
      and genotypic heterogeneity is extensive and requires careful scrutiny of its
      pattern of cancer associations, such as malignant melanoma associated with
      pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due
      to the CDKN2A germline mutation. This review is designed to depict several of the
      hereditary pancreatic cancer syndromes with particular attention given to the
      clinical application of this knowledge into improved control of pancreatic
      cancer. 

PMID- 24281206
TI  - Nanoparticles in sentinel lymph node assessment in breast cancer.
AB  - The modern management of the axilla in breast cancer relies on surgery for
      accurate staging of disease and identifying those patients at risk who would
      benefit from adjuvant chemotherapy. The introduction of sentinel lymph node
      biopsy has revolutionized axillary surgery, but still involves a surgical
      procedure with associated morbidity in many patients with no axillary
      involvement. Nanotechnology encompasses a broad spectrum of scientific
      specialities, of which nanomedicine is one. The potential use of dual-purpose
      nanoprobes could enable imaging the axilla simultaneous identification and
      treatment of metastatic disease. Whilst most applications of nanomedicine are
      still largely in the laboratory phase, some potential applications are currently
      undergoing clinical evaluation for translation from the bench to the bedside.
      This is an exciting new area of research where scientific research may become a
      reality. 

PMID- 24281204
TI  - NF-kappaB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic
      and in Microenvironmental Cells.
AB  - Two main NF-kappaB signaling pathways, canonical and noncanonical, performing
      distinct functions in organisms have been characterized. Identification of
      mutations in genes encoding components of these NF-kappaB signaling pathways in
      lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute
      lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that
      despite significant therapeutic advances can still be fatal. Although mutations
      in NF-kappaB genes have not been reported in T-ALL, NF-kappaB constitutive
      activation in human T-ALL and in acute T-cell leukemia mouse models has been
      observed. Although these studies revealed activation of members of both canonical
      and noncanonical NF-kappaB pathways in acute T-cell leukemia, only inhibition of
      canonical NF-kappaB signaling was shown to impair leukemic T cell growth. Besides
      playing an important pro-oncogenic role in leukemic T cells, NF-kappaB signaling
      also appears to modulate T-cell leukemogenesis through its action in
      microenvironmental stromal cells. This article reviews recent data on the role of
      these transcription factors in T-ALL and pinpoints further research crucial to
      determine the value of NF-kappaB inhibition as a means to treat T-ALL. 

PMID- 24281207
TI  - Radiofrequency ablation: a minimally invasive approach in kidney tumor
      management.
AB  - The management and diagnosis of renal tumors have changed significantly over the
      last decade. Due to advances in imaging techniques, more than 50% of kidney
      tumors are discovered incidentally and many of them represent an early stage
      lesion. This has stimulated the development of nephron-sparing surgery and of the
      minimally invasive treatment options including ablative techniques, i.e.,
      radiofrequency ablation (RFA) and cryoablation. The objective of the minimally
      invasive approach is to preserve the renal function and to lower the
      perioperative morbidity. RFA involves inducing the coagulative necrosis of tumor
      tissue. Being probably one of the least invasive procedures in kidney tumor
      management, RFA may be performed percutaneously under ultrasound (US), computed
      tomography (CT) or magnetic resonance (MR) guidance. Most of the studies show
      that the RFA procedure is efficient, safe and has a low complication rate. Due to
      the still limited data on the oncological outcome of RFA, the indication for this
      intervention remains limited to selected patients with small organ-confined renal
      tumors and contraindication to surgery or who have a solitary kidney. The aim of
      our study is to review the literature on RFA of kidney tumors. 

PMID- 24281208
TI  - Molecular pathogenesis of pancreatic neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the
      pancreas and arise sporadically or in the context of genetically determined
      syndromes. Depending on hormone production and sensing, PNETs clinically manifest
      due to a hormone-related syndrome (functional PNET) or by symptoms related to
      tumor bulk effects (non-functional PNET). So far, radical surgical excision is
      the only therapy to cure the disease. Development of tailored non-surgical
      approaches has been impeded by the lack of experimental laboratory models and
      there is, therefore, a limited understanding of the complex cellular and
      molecular biology of this heterogeneous group of neoplasm. This review aims to
      summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a
      cellular and molecular level. Open questions in the field of PNET research are
      discussed with specific emphasis on the relevance of disease management. 

PMID- 24281209
TI  - A comparative study of two folate-conjugated gold nanoparticles for cancer
      nanotechnology applications.
AB  - We report a comparative study of synthesis, characteristics and in vitro tests of
      two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP
      sizes for selective targeting of folate-receptor positive cancerous cells. The
      linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with
      nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the
      folate-receptor tissue distribution and its endocytosis for targeted
      nanotechnology. Comparison of the two nanoconjugates' syntheses and
      characterization is also reported, including materials and methods of synthesis,
      UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red
      (FTIR) measurements, Transmission electron microscopy (TEM) images and size
      distributions, X-ray diffraction data, elemental analyses and chemical stability
      comparison. In addition to the analytical characterization of the nanoconjugates,
      the cell lethality was measured in HeLa (high level of folate receptor
      expression) and MCF-7 (low level of folate receptor expression) cells. The
      nanoconjugates themselves, as well as the intense pulsed light (IPL) were not
      harmful to cell viability. However, upon stimulation of the folate targeted
      nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only
      ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This
      demonstrates that folate targeting is effective in selecting for specific cell
      populations. Considering the various comparisons made, we conclude that Folate
      4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy. 

PMID- 24281212
TI  - Epidemiology of skin cancer: role of some environmental factors.
AB  - The incidence rate of melanoma and non-melanoma skin cancer entities is
      dramatically increasing worldwide. Exposure to UVB radiation is known to induce
      basal and squamous cell skin cancer in a dose-dependent way and the depletion of
      stratospheric ozone has implications for increases in biologically damaging solar
      UVB radiation reaching the earth's surface. In humans, arsenic is known to cause
      cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney.
      Exposure to high levels of arsenic in drinking water has been recognized in some
      regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been
      reported to be associated with ingestion of arsenic alone or in combination with
      other risk factors. The impact of changes in ambient temperature will influence
      people's behavior and the time they spend outdoors. Higher temperatures
      accompanying climate change may lead, among many other effects, to increasing
      incidence of skin cancer. 

PMID- 24281210
TI  - Surgery as a double-edged sword: a clinically feasible approach to overcome the
      metastasis-promoting effects of surgery by blunting stress and prostaglandin
      responses.
AB  - Surgery remains an essential therapeutic approach for most solid malignancies,
      including breast cancer. However, surgery also constitutes a risk factor for
      promotion of pre-existing micrometastases and the initiation of new metastases
      through several mechanisms, including the release of prostaglandins and stress
      hormones (e.g., catecholamines and glucocorticoids). However, the perioperative
      period also presents an opportunity for cell mediated immunity (CMI) and other
      mechanisms to eradicate or control minimal residual disease, provided that the
      deleterious effects of surgery are minimized. Here, we discuss the key role of
      endogenous stress hormones and prostaglandins in promoting the metastatic process
      through their direct impact on malignant cells, and through their deleterious
      impact on anti-cancer CMI. We further discuss the effects of anesthetic
      techniques, the extent of surgery, pain alleviation, and timing within the
      menstrual cycle with respect to their impact on tumor recurrence and
      physiological stress responses. Last, we suggest an attractive perioperative drug
      regimen, based on a combination of a cyclooxygenase (COX)-2 inhibitor and a beta
      adrenergic blocker, which we found effective in attenuating immune suppression
      and the metastasis-promoting effects of surgery in several tumor models. This
      regimen is clinically applicable, and could potentially promote disease free
      survival in patients operated for breast and other types of cancer. 

PMID- 24281213
TI  - Selection and outcome of portal vein resection in pancreatic cancer.
AB  - Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five
      year survival of pancreatic cancer after pancreatectomy is very low, and surgical
      resection is the only option to cure this dismal disease. The standard surgical
      procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity
      and especially the mortality of PD have been greatly reduced. Portal vein
      resection in pancreatic cancer surgery is one attempt to increase resectability
      and radicality, and the procedure has become safe to perform.
      Clinicohistopathological studies have shown that the most important indication
      for portal vein resection in patients with pancreatic cancer is the ability to
      obtain cancer-free surgical margins. Otherwise, portal vein resection is
      contraindicated. 

PMID- 24281211
TI  - The enigmatic roles of caspases in tumor development.
AB  - One function ascribed to apoptosis is the suicidal destruction of potentially
      harmful cells, such as cancerous cells. Hence, their growth depends on evasion of
      apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is
      ultimately carried out by the sequential activation of initiator and executioner
      caspases, which constitute a family of intracellular proteases involved in
      dismantling the cell in an ordered fashion. In cancer, therefore, one would
      anticipate caspases to be frequently rendered inactive, either by gene silencing
      or by somatic mutations. From clinical data, however, there is little evidence
      that caspase genes are impaired in cancer. Executioner caspases have only rarely
      been found mutated or silenced, and also initiator caspases are only affected in
      particular types of cancer. There is experimental evidence from transgenic mice
      that certain initiator caspases, such as caspase-8 and -2, might act as tumor
      suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway,
      caspase-9, however, did not promote cellular transformation. These data seem to
      question a general tumor-suppressive role of caspases. We discuss several
      possible ways how tumor cells might evade the need for alterations of caspase
      genes. First, alternative splicing in tumor cells might generate caspase variants
      that counteract apoptosis. Second, in tumor cells caspases might be kept in check
      by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream
      of caspase activation might be disrupted in tumor cells. Finally, caspase
      independent cell death mechanisms might abrogate the selection pressure for
      caspase inactivation during tumor development. These scenarios, however, are
      hardly compatible with the considerable frequency of spontaneous apoptosis
      occurring in several cancer types. Therefore, alternative concepts might come
      into play, such as compensatory proliferation. Herein, apoptosis and/or non
      apoptotic functions of caspases may even promote tumor development. Moreover,
      experimental evidence suggests that caspases might play non-apoptotic roles in
      processes that are crucial for tumorigenesis, such as cell proliferation,
      migration, or invasion. We thus propose a model wherein caspases are preserved in
      tumor cells due to their functional contributions to development and progression
      of tumors. 

PMID- 24281214
TI  - Definition of microscopic tumor clearance (r0) in pancreatic cancer resections.
AB  - To date, curative resection is the only chance for cure for patients suffering
      from pancreatic ductal adenoacarcinoma (PDAC). Despite low reported rates of
      microscopic tumor infiltration (R1) in most studies, tumor recurrence is a common
      finding in patients with PDAC and contributes to extremely low long-term survival
      rates. Lack of international definition of resection margins and of standardized
      protocols for pathological examination lead to high variation in reported R1
      rates. Here we review recent studies supporting the hypothesis that R1 rates are
      highly underestimated in certain studies and that a microscopic tumor clearance
      of at least 1 mm is required to confirm radicality and to serve as a reliable
      prognostic and predictive factor. 

PMID- 24281215
TI  - A Distinct Slow-Cycling Cancer Stem-like Subpopulation of Pancreatic
      Adenocarcinoma Cells is maintained in Vivo.
AB  - Pancreatic adenocarcinoma has the worst prognosis of any major malignancy, with. 

PMID- 24281216
TI  - Possible role of autophagy in the treatment of pancreatic cancer with histone
      deacetylase inhibitors.
AB  - Pancreatic cancer is a lethal disease and notoriously difficult to treat. Only a
      small proportion is curative by surgical resection, whilst standard chemotherapy
      for patients with advanced disease has only a modest effect with substantial
      toxicity. Clearly there is a need for the continual development of novel
      therapeutic agents to improve the current situation. Currently, there is a bulk
      of data indicating the important function of autophagy in cancer. While genetic
      evidence indicates that autophagy functions as a tumor suppressor, it is also
      apparent that autophagy can promote the survival of established tumors under
      stress conditions and in response to chemotherapy. This review provides a
      spectrum of potential pharmacological agents and autophagic approaches to enhance
      cell killing in pancreatic cancer. 

PMID- 24281217
TI  - Human Equilibrative Nucleoside Transporter 1 (hENT1) in Pancreatic
      Adenocarcinoma: Towards Individualized Treatment Decisions.
AB  - Pancreatic cancer is one of the most lethal cancers, where curative surgical
      resections are rare and less than 5% of patients experience long-term survival.
      Despite numerous clinical trials, improvements in the systemic treatment of this
      disease have been limited. Gemcitabine, a nucleoside analogue, is still
      considered the standard of care chemotherapy for most patients in the advanced
      disease setting. To exert its cytotoxic effects, gemcitabine must enter cells via
      nucleoside transporters, most notably human equilibrative nucleoside transporter
      1 (hENT1). Increasingly strong evidence suggests hENT1 is a prognostic biomarker
      in gemcitabine-treated pancreatic cancer, and may well be a predictive biomarker
      of gemcitabine efficacy. In this review, we synthesize the literature surrounding
      hENT1 in pancreatic cancer, identify the key outstanding questions, and suggest
      strategies to prospectively evaluate the clinical utility of hENT1 in future
      clinical studies. 

PMID- 24281219
TI  - Contribution of epithelial-mesenchymal transition to pancreatic cancer
      progression.
AB  - Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies,
      with median survival of less than one year and overall five-year survival of less
      than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal
      transition (EMT) contributes to pancreatic cancer metastasis and to treatment
      resistance. In this review, we will examine the data demonstrating the role and
      regulation of EMT in pancreatic cancer progression, focusing particularly on the
      transcription factors and microRNAs involved in EMT. We will examine how EMT is
      involved in the generation and maintenance of stem cells, and the role of EMT in
      modulating resistance of PDAC cells to drug therapies. We will also identify
      putative EMT-targeting agents that may help to reduce the morbidity and mortality
      associated with pancreatic cancer. 

PMID- 24281218
TI  - Epithelial-mesenchymal transition in pancreatic carcinoma.
AB  - Pancreatic carcinoma is the fourth-leading cause of cancer death and is
      characterized by early invasion and metastasis. The developmental program of
      epithelial-mesenchymal transition (EMT) is of potential importance for this rapid
      tumor progression. During EMT, tumor cells lose their epithelial characteristics
      and gain properties of mesenchymal cells, such as enhanced motility and invasive
      features. This review will discuss recent findings pertinent to EMT in pancreatic
      carcinoma. Evidence for and molecular characteristics of EMT in pancreatic
      carcinoma will be outlined, as well as the connection of EMT to related topics,
      e.g., cancer stem cells and drug resistance. 

PMID- 24281222
TI  - Assessment of factors associated with dose differences between Japan and the
      United States.
AB  - Although it is well known that there are differences in approved doses between
      Japan and the United States, there has been no comprehensive research into the
      causes thereof. This study furthers the discussion of our previous investigation
      in 2010, with particular focus on pharmaceutical industry strategy and regulatory
      policy, among drugs approved in Japan between 2001 and 2009. Dose differences
      were observed in 73 of 190 drugs. Non-Japanese firms were more likely to have a
      similar dose approved between Japan and the United States, the association being
      more pronounced when limiting the analysis to drugs for which a Japanese dose
      finding study was not conducted. Furthermore, dose differences were less frequent
      when non-Japanese efficacy data were included in the application data package. No
      relation between potential intrinsic ethnic difference and dose difference could
      be identified. The results suggest that the pathway of drug development is more
      strongly associated with dose difference than are drug characteristics. 

PMID- 24281221
TI  - Hypoxia induced tumor metabolic switch contributes to pancreatic cancer
      aggressiveness.
AB  - Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid
      tumors with an overall five-year survival rate of only 3-5%. Its aggressive
      biology and resistance to conventional and targeted therapeutic agents lead to a
      typical clinical presentation of incurable disease once diagnosed. The disease is
      characterized by the presence of a dense stroma of fibroblasts and inflammatory
      cells, termed desmoplasia, which limits the oxygen diffusion in the organ,
      creating a strong hypoxic environment within the tumor. In this review, we argue
      that hypoxia is responsible for the highly aggressive and metastatic
      characteristics of this tumor and drives pancreatic cancer cells to oncogenic and
      metabolic changes facilitating their proliferation. However, the molecular
      changes leading to metabolic adaptations of pancreatic cancer cells remain
      unclear. Cachexia is a hallmark of this disease and illustrates that this cancer
      is a real metabolic disease. Hence, this tumor must harbor metabolic pathways
      which are probably tied in a complex inter-organ dialog during the development of
      this cancer. Such a hypothesis would better explain how under fuel source
      limitation, pancreatic cancer cells are maintained, show a growth advantage, and
      develop metastasis. 

PMID- 24281220
TI  - Treatment of brain metastasis from lung cancer.
AB  - Brain metastases are not only the most common intracranial neoplasm in adults but
      also very prevalent in patients with lung cancer. Patients have been grouped into
      different classes based on the presence of prognostic factors such as control of
      the primary tumor, functional performance status, age, and number of brain
      metastases. Patients with good prognosis may benefit from more aggressive
      treatment because of the potential for prolonged survival for some of them. In
      this review, we will comprehensively discuss the therapeutic options for treating
      brain metastases, which arise mostly from a lung cancer primary. In particular,
      we will focus on the patient selection for combined modality treatment of brain
      metastases, such as surgical resection or stereotactic radiosurgery (SRS)
      combined with whole brain irradiation; the use of radiosensitizers; and the
      neurocognitive deficits after whole brain irradiation with or without SRS. The
      benefit of prophylactic cranial irradiation (PCI) and its potentially associated
      neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung
      cancer (NSCLC) are also discussed, along with the combined treatment of
      intrathoracic primary disease and solitary brain metastasis. The roles of SRS to
      the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated
      boost to the gross brain metastases, as well as combining WBRT with epidermal
      growth factor receptor (EGFR) inhibitors, are explored as well. 

PMID- 24281223
TI  - Understanding stroke survivorship: expanding the concept of poststroke
      disability.
AB  - BACKGROUND AND PURPOSE: Limitations in essential daily activities are common
      among older adults after stroke, but little is known about restrictions in their
      ability to participate in valued social activities. We sought to broaden our
      understanding of disability after stroke by characterizing poststroke
      participation restrictions and investigating the extent to which they are
      accounted for by differences in physical and cognitive capacity,
      aphasia/dysarthria, depressive, and anxiety symptoms. METHODS: Data from the 2011
      National Health and Aging Trends Study (NHATS) were used to identify 892 self
      reported stroke survivors aged>=65 years. One-to-one propensity matching was
      performed on demographics and comorbidities to create a matched sample.
      Participation restrictions were defined as reductions/absence in social
      activities valued by respondents because of their health or functioning. Physical
      and cognitive capacity, depressive and anxiety symptoms were measured by
      validated scales and aphasia/dysarthria by a single question. Comparisons using
      survey-weighted chi2 tests and logistic regression were made. RESULTS: Stroke
      survivors had more participation restrictions (32.8% versus 23.5%; odds ratio,
      1.59; 95% confidence interval, 1.28-1.95; P<0.01) than controls. Differences
      between stroke survivors and controls in any participation restriction and
      several components (attending religious service, clubs/classes, and going out for
      enjoyment) were eliminated after adjusting for physical capacity. Depressive and
      anxiety symptoms and aphasia/dysarthria were independent predictors of
      participation restrictions. CONCLUSIONS: Stroke survivors have more participation
      restrictions than can be accounted for by sociodemographic profiles and
      comorbidity burden. Future work aimed at improving physical capacity, reducing
      depressive and anxiety symptoms, and improving aphasia/dysarthria has potential
      to enhance participation.

PMID- 24281224
TI  - Design and validation of a prehospital stroke scale to predict large arterial
      occlusion: the rapid arterial occlusion evaluation scale.
AB  - BACKGROUND AND PURPOSE: We aimed to develop and validate a simple prehospital
      stroke scale to predict the presence of large vessel occlusion (LVO) in patients
      with acute stroke. METHODS: The Rapid Arterial oCclusion Evaluation (RACE) scale
      was designed based on the National Institutes of Health Stroke Scale (NIHSS)
      items with a higher predictive value of LVO on a retrospective cohort of 654
      patients with acute ischemic stroke: facial palsy (scored 0-2), arm motor
      function (0-2), leg motor function (0-2), gaze (0-1), and aphasia or agnosia (0
      2). Thereafter, the RACE scale was validated prospectively in the field by
      trained medical emergency technicians in 357 consecutive patients transferred by
      Emergency Medical Services to our Comprehensive Stroke Center. Neurologists
      evaluated stroke severity at admission and LVO was diagnosed by transcranial
      duplex, computed tomography, or MR angiography. Receiver operating curve,
      sensitivity, specificity, and global accuracy of the RACE scale were analyzed to
      evaluate its predictive value for LVO. RESULTS: In the prospective cohort, the
      RACE scale showed a strong correlation with NIHSS (r=0.76; P<0.001). LVO was
      detected in 76 of 357 patients (21%). Receiver operating curves showed a similar
      capacity to predict LVO of the RACE scale compared with the NIHSS (area under the
      curve 0.82 and 0.85, respectively). A RACE scale>=5 had sensitivity 0.85,
      specificity 0.68, positive predictive value 0.42, and negative predictive value
      0.94 for detecting LVO. CONCLUSIONS: The RACE scale is a simple tool that can
      accurately assess stroke severity and identify patients with acute stroke with
      large artery occlusion at prehospital setting by medical emergency technicians.

PMID- 24281225
TI  - Preadmission oral anticoagulant treatment and clinical outcome among patients
      hospitalized with acute stroke and atrial fibrillation: a nationwide study.
AB  - BACKGROUND AND PURPOSE: Preadmission oral anticoagulant treatment (OAT) has been
      linked with less severe stroke and a better outcome in patients with atrial
      fibrillation. However, the existing studies have methodological limitations and
      have, with one exception, not included hemorrhagic strokes. We performed a
      nationwide historic follow-up study using data from population-based healthcare
      registries to assess the effect of preadmission OAT on stroke outcomes further.
      METHODS: We identified 11 356 patients with atrial fibrillation admitted to
      hospital with acute stroke (including ischemic stroke and intracerebral
      hemorrhage) between 2003 and 2009. Propensity score-matched analyses were used to
      compare stroke severity (Scandinavian Stroke Scale score) and mortality among
      2175 patients with preadmission OAT and 2175 patients without preadmission OAT.
      RESULTS: A total of 2492 (21.9%) patients received OAT at the time of their
      stroke. Preadmission OAT was associated with a lower risk of severe stroke
      (Scandinavian Stroke Scale score at time of admission, <30 point; propensity
      score-matched odds ratio, 0.74; 95% confidence interval, 0.63-0.86) and lower 30
      day mortality rate (propensity score-matched adjusted odds ratio, 0.83; 95%
      confidence interval, 0.71-0.98). CONCLUSIONS: Only a minority of hospitalized
      patients with acute stroke with atrial fibrillation received OAT at the time of
      stroke. Preadmission OAT was associated with less severe stroke and lower 30-day
      mortality rate in a propensity score-matched analysis.

PMID- 24281226
TI  - Multicenter accuracy and interobserver agreement of spot sign identification in
      acute intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Rapid, accurate, and reliable identification of the
      computed tomography angiography spot sign is required to identify patients with
      intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to
      assess the accuracy and interobserver agreement for spot sign identification.
      METHODS: A total of 131 neurology, emergency medicine, and neuroradiology staff
      and fellows underwent imaging certification for spot sign identification before
      enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage
      for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral
      hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for
      evaluation of spot sign presence, number, and mimics. True spot positivity was
      determined by consensus of 2 experienced neuroradiologists. Diagnostic
      performance, agreement, and differences by training level were analyzed. RESULTS:
      Mean accuracy, sensitivity, and specificity for spot sign identification were
      87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity
      (P<0.001) because of true spot signs incorrectly perceived as spot mimics.
      Interobserver agreement for spot sign presence was moderate (k=0.60). When true
      spots were correctly identified, 81% correctly identified the presence of single
      or multiple spots. Median time needed to evaluate the presence of a spot sign was
      1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance,
      interobserver agreement, and time needed for spot sign evaluation were similar
      among staff physicians and fellows. CONCLUSIONS: Accuracy for spot identification
      is high with opportunity for improvement in spot interpretation sensitivity and
      interobserver agreement particularly through greater reliance on computed
      tomography angiography source data and awareness of limitations of multiplanar
      images. Further prospective study is needed.

PMID- 24281227
TI  - American Stroke Association Stroke Council update.

PMID- 24281229
TI  - Relative cerebral blood volume as a marker of durable tissue-at-risk viability in
      hyperacute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Selection of best responders to reperfusion therapies
      could be aided by predicting the duration of tissue-at-risk viability, which may
      be dependant on collateral circulation status. We aimed to identify the best
      predictor of good collateral circulation among perfusion computed tomography
      (PCT) parameters in middle cerebral artery (MCA) ischemic stroke and to analyze
      how early MCA response to intravenous thrombolysis and PCT-derived markers of
      good collaterals interact to determine stroke outcome. METHODS: We prospectively
      studied patients with acute MCA ischemic stroke treated with intravenous
      thrombolysis who underwent PCT before treatment showing a target mismatch
      profile. Collateral status was assessed using a PCT source image-based score. PCT
      maps were quantitatively analyzed. Cerebral blood volume (CBV), cerebral blood
      flow, and Tmax were calculated within the hypoperfused volume and in the
      equivalent region of unaffected hemisphere. Occluded MCAs were monitored by
      transcranial Duplex to assess early recanalization. Main outcome variables were
      brain hypodensity volume and modified Rankin scale score at day 90. RESULTS: One
      hundred patients with MCA ischemic stroke imaged by PCT received intravenous
      thrombolysis, and 68 met all inclusion criteria. A relative CBV (rCBV) >0.93
      emerged as the only predictor of good collaterals (odds ratio, 12.6; 95%
      confidence interval, 2.9-55.9; P=0.001). Early MCA recanalization was associated
      with better long-term outcome and lower infarct volume in patients with
      rCBV<0.93, but not in patients with high rCBV. None of the patients with
      rCBV<0.93 achieved good outcome in absence of early recanalization. CONCLUSIONS:
      High rCBV was the strongest marker of good collaterals and may characterize
      durable tissue-at-risk viability in hyperacute MCA ischemic stroke.

PMID- 24281230
TI  - Late stroke: comparison of percutaneous coronary intervention versus coronary
      artery bypass grafting in patients with multivessel disease and unprotected left
      main disease: a meta-analysis and review of literature.
AB  - BACKGROUND AND PURPOSE: Studies have suggested that the early excess risk of
      stroke in coronary artery bypass grafting (CABG) may be compensated for by a slow
      but progressive catch-up phenomenon in patients undergoing percutaneous coronary
      intervention (PCI). We therefore undertook this analysis to compare the temporal
      stroke risk between PCI and CABG in patients with unprotected left main stenosis
      and multivessel coronary artery disease. METHODS: Studies of PCI versus CABG for
      unprotected left main stenosis and multivessel disease published between January
      1994 (stent era) and July 2013 were identified using an electronic search and
      reviewed using meta-analytic techniques. RESULTS: We selected 57 reports for the
      meta-analysis by applying the inclusion and exclusion criteria. The analysis was
      performed on 80,314 patient records. There was a significantly lower risk of
      cumulative stroke in patients undergoing PCI with stenting at 1 year (odds ratio
      [OR], 0.55; 95% confidence interval [CI], 0.42-0.71), 2 years (OR, 0.78; 95% CI,
      0.66-0.92), 3 years (OR, 0.79; 95% CI, 0.67-0.92), 4 years (OR, 0.74; 95% CI,
      0.56-0.97), and 5 years (OR, 0.79; 95% CI, 0.69-0.91). There was no significant
      difference in the incidence of stroke because of the small sample size (OR, 0.71;
      95% CI, 0.46-1.08) at >5 years between PCI and CABG. Similar results were
      observed on subgroup analysis (multi-vessel coronary artery disease, unprotected
      left main, diabetics, and randomized trials) and for stroke within 30 days. Late
      stroke (stroke>30 days) was similar between the 2 groups. CONCLUSIONS: There is a
      significantly lower risk of stroke within 30 days and cumulative stroke with PCI
      as compared with CABG up to year 5. There is no late catch up of stroke in the
      PCI arm. The risk of stroke should be weighed in deciding between
      revascularization strategies.

PMID- 24281232
TI  - Arginase-1: a highly specific marker separating pancreatic adenocarcinoma from
      hepatocellular carcinoma.
AB  - BACKGROUND: Arginase-1 and HepPar-1 are effective immunohistochemical (IHC)
      markers for hepatocellular carcinoma (HCC). In this study, we explored the
      possible efficacy of these stains in diagnosing pancreatic adenocarcinoma (PAD).
      STUDY DESIGN: Arginase-1 and HepPar-1 IHC was performed on formalin-fixed,
      paraffin-embedded fine needle aspiration (FNA) cell blocks (CB) of PAD (n = 46),
      tissue microarray (TMA) of PAD (n = 33), FNA CB of HCC (n = 44) and TMA of HCC (n
      = 85). Negative controls without carcinoma were also applied (pancreas CB, n = 7;
      pancreas TMA, n = 3). RESULTS: PAD CB demonstrated arginase-1 positivity in 0 of
      46 cases and HepPar-1 positivity in 7 of 46 cases (15%). PAD TMA demonstrated
      arginase-1 positivity in 0 of 33 cases and HepPar-1 positivity in 4 of 33 cases
      (12%). HCC CB demonstrated arginase-1 positivity in 37 of 44 cases (84%) and
      HepPar-1 positivity in 32 of 44 cases (72%). HCC TMA demonstrated arginase-1
      positivity in 75 of 85 cases (88%) and HepPar-1 positivity in 80 of 85 cases
      (94%). CONCLUSION: Both arginase-1 and HepPar-1 are effective IHC markers of
      hepatocellular differentiation. Arginase-1 demonstrates superior sensitivity and
      specificity compared with HepPar-1 in the diagnosis of HCC. However, both
      arginase-1 and HepPar-1 have a low sensitivity and a very high specificity for
      PAD.

PMID- 24281231
TI  - Pediatric intracerebral hemorrhage score: a simple grading scale for
      intracerebral hemorrhage in children.
AB  - BACKGROUND AND PURPOSE: The intracerebral hemorrhage (ICH) score is the most
      commonly used clinical grading scale for outcome prediction after adult ICH. We
      created a similar scale in children to inform clinical care and assist in
      clinical research. METHODS: Children, full-term newborns to 18 years, with
      spontaneous ICH were prospectively enrolled from 2007 to 2012 at 3 centers. The
      pediatric ICH score was created by identifying factors associated with poor
      outcome. The score's ability to detect moderate disability or worse and severe
      disability or death was examined with sensitivity, specificity, and area under
      the receiver operating characteristic curve. RESULTS: The pediatric ICH score
      components include ICH volume>2% to 3.99% of total brain volume (TBV): 1 point;
      ICH volume>=4% TBV: 2 points; acute hydrocephalus: 1 point; herniation: 1 point;
      and infratentorial location: 1 point. The score ranges from 0 to 5. At 3-month
      follow-up of 60 children, 10 were severely disabled or dead, 30 had moderate
      disability, and 20 had good recovery. A pediatric ICH score>=1 predicted moderate
      disability or worse with a sensitivity of 75% (95% confidence interval [CI], 59%
      to 87%) and a specificity of 70% (95% CI, 46% to 88%). A pediatric ICH score>=2
      predicted severe disability or death with a sensitivity and specificity of 90%
      (95% CI, 55% to 99%) and 68% (95% CI, 53% to 80%), respectively. The area under
      the receiver operating characteristic curve for classifying outcome as severe
      disability or death was 0.88 (95% CI, 0.78-0.97). CONCLUSIONS: The pediatric ICH
      score is a simple clinical grading scale that may ultimately be used for risk
      stratification, clinical care, and research.

PMID- 24281233
TI  - Synthesis of functionalized insulated molecular wires by polymerization of an
      insulated pi-conjugated monomer.
AB  - A new method for the synthesis of an insulated pi-conjugated monomer was
      developed via the sequential self-inclusion followed by the elongation of the pi
      conjugated unit. The monomer was utilized in the synthesis of stimuli-responsive
      insulated molecular wires. 

PMID- 24281234
TI  - Beyond the randomized clinical trial: citrate for continuous renal replacement
      therapy in clinical practice.
AB  - BACKGROUND: Premature circuit clotting is a major problem during continuous renal
      replacement therapy (CRRT). Six randomized controlled trials confirmed that
      regional anticoagulation with citrate is superior to heparin. Our objective was
      to compare circuit patency with citrate, heparin and epoprostenol in routine
      clinical practice. METHODS: We retrospectively analysed data on circuit patency
      of all circuits used in a single centre between September 2008 and August 2009.
      We differentiated between premature filter clotting, elective discontinuation and
      waste. RESULTS: 309 patients were treated with CRRT (n = 2,059 circuits). The
      mean age was 65.7; 63.8% were male. The methods to maintain circuit patency were
      unfractionated heparin (42.3%), epoprostenol (23.0%), citrate (14.7%),
      combinations of different anticoagulants (14.6%) and no anticoagulation (4.7%).
      Premature clotting was the most common reason for circuit discontinuation among
      circuits anticoagulated with heparin, epoprostenol or combinations of different
      anticoagulants (59-62%). Among circuits anticoagulated with citrate the main
      reason for discontinuation was elective (61%). Hazard regression analysis
      confirmed significantly better circuit survival with citrate. Changing from
      heparin to citrate decreased the risk of premature circuit clotting by 75.8%.
      CONCLUSION: In routine clinical practice, regional anticoagulation with citrate
      is associated with significantly better circuit patency than heparin or
      epoprostenol.

PMID- 24281235
TI  - Polyoxometalate supported complexes as effective electron-transfer mediators in
      dye-sensitized solar cells.
AB  - Two Anderson-type heteropolyanion-supported copper phenanthroline redox couples
      have been successfully introduced into dye-sensitized solar cells, which can
      significantly increase the short-circuit photocurrent, open-circuit voltage and
      the conversion efficiency by 2.2 times, 26.8% and 3.93 times respectively,
      compared to the pristine copper phenanthroline redox couple. 

PMID- 24281236
TI  - Efficacy and safety of flibanserin in postmenopausal women with hypoactive sexual
      desire disorder: results of the SNOWDROP trial.
AB  - OBJECTIVE: This study aimed to assess the efficacy and safety of flibanserin, a
      serotonin receptor 1A agonist/serotonin receptor 2A antagonist, in postmenopausal
      women with hypoactive sexual desire disorder (HSDD). METHODS: Naturally
      postmenopausal women with HSDD received flibanserin 100 mg once daily at bedtime
      (n = 468) or placebo (n = 481) for 24 weeks. Co-primary endpoints were changes
      from baseline to week 24 in the number of satisfying sexual events (SSEs) across
      28 days and in the Female Sexual Function Index (FSFI) desire domain score.
      Secondary endpoints included change from baseline in Female Sexual Distress Scale
      Revised (FSDS-R) Item 13 score (which assesses distress due to low sexual
      desire), FSDS-R total score, and FSFI total score. The Patient Benefit Evaluation
      was asked on treatment discontinuation. RESULTS: There were significant
      improvements with flibanserin versus placebo in the mean (SE) changes in the
      number of SSEs (1.0 [0.1] vs 0.6 [0.1]), FSFI desire domain score (0.7 [0.1] vs
      0.4 [0.1]), FSDS-R Item 13 score (-0.8 [0.1] vs -0.6 [0.1]), FSDS-R total score (
      8.3 [0.6] vs -6.3 [0.6]), and FSFI total score (4.2 [0.4] vs 2.7 [0.4]; all P <
      0.01). More women on flibanserin (37.6%) than women on placebo (28.0%) reported
      experiencing meaningful benefits from the study medication on treatment
      discontinuation. The most frequent adverse events associated with flibanserin
      were dizziness, somnolence, nausea, and headache. CONCLUSIONS: In naturally
      postmenopausal women with HSDD, flibanserin, compared with placebo, has been
      associated with improvement in sexual desire, improvement in the number of SSEs,
      and reduced distress associated with low sexual desire, and is well tolerated.

PMID- 24281238
TI  - Re: Raloxifene and stroke risks in Japanese postmenopausal women with
      osteoporosis on postmarketing surveillance.

PMID- 24281239
TI  - C-H functionalization directed by transformable nitrogen heterocycles: synthesis
      of ortho-oxygenated arylnaphthalenes from arylphthalazines.
AB  - Two protocols for oxygenation of aromatic C-H bonds ortho-positioned to the
      phthalazine ring were developed. The transannulation of the phthalazine ring to a
      naphthalene moiety by an Inverse Electron Demand Diels-Alder (IEDDA) reaction led
      to the synthesis of naphtho[2,1-c]chromenes, 1-(ortho-hydroxyaryl)naphthalenes
      and 6,7-dihydrobenzo[b]naphtho[1,2-d]oxepine. This new strategy based on the
      utilization of transformable nitrogen heterocycles in C-H functionalization
      chemistry can be potentially applicable to the synthesis of a broad range of
      biaryl compounds. 

PMID- 24281237
TI  - Testosterone dose-response relationships in hysterectomized women with or without
      oophorectomy: effects on sexual function, body composition, muscle performance
      and physical function in a randomized trial.
AB  - OBJECTIVE: This study aims to determine the dose-dependent effects of
      testosterone on sexual function, body composition, muscle performance, and
      physical function in hysterectomized women with or without oophorectomy. METHODS:
      Seventy-one postmenopausal women who previously underwent hysterectomy with or
      without oophorectomy and had total testosterone levels less than 31 ng/dL or free
      testosterone levels less than 3.5 pg/mL received a standardized transdermal
      estradiol regimen during the 12-week run-in period and were randomized to receive
      weekly intramuscular injections of placebo or 3, 6.25, 12.5, or 25 mg of
      testosterone enanthate for 24 weeks. Total and free testosterone levels were
      measured by liquid chromatography-tandem mass spectrometry and equilibrium
      dialysis, respectively. The primary outcome was change in sexual function
      measured by the Brief Index of Sexual Functioning for Women. Secondary outcomes
      included changes in sexual activity, sexual distress, Derogatis Interview for
      Sexual Functioning, lean body mass, fat mass, muscle strength and power, and
      physical function. RESULTS: Seventy-one women were randomized; five groups were
      similar at baseline. Sixty-two women with analyzable data for the primary outcome
      were included in the final analysis. The mean on-treatment total testosterone
      concentrations were 19, 78, 102, 128, and 210 ng/dL in the placebo, 3-mg, 6.25
      mg, 12.5-mg, and 25-mg groups, respectively. Changes in composite Brief Index of
      Sexual Functioning for Women scores, thoughts/desire, arousal, frequency of
      sexual activity, lean body mass, chest-press power, and loaded stair-climb power
      were significantly related to increases in free testosterone concentrations;
      compared with placebo, changes were significantly greater in women assigned to
      the 25-mg group, but not in women in the lower-dose groups. Sexual activity
      increased by 2.7 encounters per week in the 25-mg group. The frequency of
      androgenic adverse events was low. CONCLUSIONS: Testosterone administration in
      hysterectomized women with or without oophorectomy for 24 weeks was associated
      with dose and concentration-dependent gains in several domains of sexual
      function, lean body mass, chest-press power, and loaded stair-climb power. Long
      term trials are needed to weigh improvements in these outcomes against potential
      long-term adverse effects.

PMID- 24281240
TI  - Signal changes on T2*-weighted magnetic resonance imaging from the acute to
      chronic phases in patients with subarachnoid hemorrhage.
AB  - BACKGROUND: Timing of the onset of subarachnoid hemorrhage (SAH) is important for
      treatment decision-making, especially as some patients visit hospital several
      weeks after the onset of SAH. T2*-weighted (T2*W) magnetic resonance (MR) imaging
      is regarded as a sensitive method for the detection of deoxyhemoglobin or
      hemosiderin deposits. This study investigated the characteristics of the abnormal
      low intensity changes on T2*W imaging in patients with SAH, how long the abnormal
      low intensity persisted, and whether the day of onset could be predicted based on
      the T2*W imaging changes. METHODS: The study included patients treated for SAH
      associated with ruptured cerebral aneurysms, or who had previously suffered such
      SAH and were followed up at our hospital, between 2006 and 2007. MR imaging was
      performed using a whole-body 3.0-tesla MR scanner. All patients underwent
      gradient recalled echo (GRE) and echo planar (EP) T2*W imaging. The strength of
      the low intensity areas was evaluated as the following 5 grades: grade 0, no
      abnormal low intensity on both GRE and EP T2*W images; grade 1, no abnormal
      intensity on GRE T2*W images and low intensity on EP T2*W images; grade 2, spotty
      abnormal low intensity on both GRE and EP T2*W images; grade 3, medium abnormal
      low intensity (<5 mm) on both GRE and EP T2*W images, and grade 4, large abnormal
      low intensity (>=5 mm) on both GRE and EP T2*W images. RESULTS: A total of 50
      patients with 74 MR images were included during the study period. Abnormal low
      intensity on T2*W imaging was observed in all patients. The T2* score gradually
      decreased from the onset of SAH until day 90, showing a significant negative
      linear correlation (R(2) = 0.25, p = 0.0002). On the other hand, the T2* score
      did not change after 1 year. The square correlation coefficient between the
      recorded and calculated days from the onset of SAH was 0.29 (p = 0.0107). The
      pure error was +/-10 days. CONCLUSION: The T2* score gradually decreased until 90
      days from the onset of SAH, but persisted for 16 years after the onset. We could
      predict the day of onset with pure error +/-10 days in patients with SAH within
      90 days of onset using our grading system for T2*W images.

PMID- 24281241
TI  - Vascular endothelial growth factor improves liver regeneration and survival after
      90% hepatectomy in a rat model of diet-induced steatosis.
AB  - BACKGROUND/AIMS: Fatty liver disease increases the risk in major liver resection
      for patients. As previous studies suggested that vascular endothelial growth
      factor (VEGF) and erythropoietin (EPO) might improve liver regeneration in
      nonobese animals, we investigated their effect after subtotal hepatectomy (SH) in
      rats with diet-induced steatosis. METHODS: Male Wistar rats were fed with fatty
      liver-inducing diet (FLD) or normal diet (control) for 11-12 weeks followed by
      90% SH. Animals were treated either with EPO, VEGF or NaCl on postoperative days
      0, 1 and 3 and sacrificed 24 h or 7 days after SH. Survival rate, liver
      regeneration and biochemical markers were assessed. Expression of inflammatory
      cytokines (TNF-alpha, IL-6) and apoptosis-related genes (PUMA, Bcl-2) was
      measured by qRT-PCR. RESULTS: Seven-day survival after SH was significantly
      decreased in the FLD group compared to controls (50 vs. 100%, p < 0.05). In FLD
      animals, treatment with VEGF increased 7-day survival to 90% compared to only 40%
      in the EPO group. After surgery, blood glucose levels of VEGF but not EPO- or
      NaCl-treated animals remained normal. Inflammatory genes were markedly
      upregulated in the EPO group 24 h after SH. CONCLUSIONS: Steatosis severely
      impairs survival and regeneration after extensive liver resection, which can be
      counteracted at least in part by perioperative treatment with VEGF.

PMID- 24281242
TI  - Temporal channels and disparity representations in stereoscopic depth perception.
AB  - Stereoscopic depth perception is supported by a combination of correlation-based
      and match-based representations of binocular disparity. It also relies on both
      transient and sustained temporal channels of the visual system. Previous studies
      suggest that the relative contribution of the correlation-based representation
      (over the match-based representation) and the transient channel (over the
      sustained channel) to depth perception increases with the disparity magnitude.
      The mechanisms of the correlation-based and match-based representations may
      receive preferential inputs from the transient and sustained channels,
      respectively. We examined near/far discrimination by observers using random-dot
      stereograms refreshed at various rates. The relative contribution of the two
      representations was inferred by changing the fraction of dots that were contrast
      reversed between the two eyes. Both representations contributed to depth
      discrimination over the tested range of refresh rates. As the rate increased, the
      correlation-based representation increased its contribution to near/far
      discrimination. Another experiment revealed that the match-based representation
      was constructed by exploiting the variability in correlation-based disparity
      signals. Thus, the relative weight of the transient over sustained channel
      differs between the two representations. The correlation-based representation
      dominates depth perception with dynamic inputs. The match-based representation,
      which may be a nonlinear refinement of the correlation-based representation,
      exerts more influence on depth perception with slower inputs. 

PMID- 24281243
TI  - A proto-object-based computational model for visual saliency.
AB  - State-of-the-art bottom-up saliency models often assign high saliency values at
      or near high-contrast edges, whereas people tend to look within the regions
      delineated by those edges, namely the objects. To resolve this inconsistency, in
      this work we estimate saliency at the level of coherent image regions. According
      to object-based attention theory, the human brain groups similar pixels into
      coherent regions, which are called proto-objects. The saliency of these proto
      objects is estimated and incorporated together. As usual, attention is given to
      the most salient image regions. In this paper we employ state-of-the-art computer
      vision techniques to implement a proto-object-based model for visual attention.
      Particularly, a hierarchical image segmentation algorithm is used to extract
      proto-objects. The two most powerful ways to estimate saliency, rarity-based and
      contrast-based saliency, are generalized to assess the saliency at the proto
      object level. The rarity-based saliency assesses if the proto-object contains
      rare or outstanding details. The contrast-based saliency estimates how much the
      proto-object differs from the surroundings. However, not all image regions with
      high contrast to the surroundings attract human attention. We take this into
      account by distinguishing between external and internal contrast-based saliency.
      Where the external contrast-based saliency estimates the difference between the
      proto-object and the rest of the image, the internal contrast-based saliency
      estimates the complexity of the proto-object itself. We evaluate the performance
      of the proposed method and its components on two challenging eye-fixation
      datasets (Judd, Ehinger, Durand, & Torralba, 2009; Subramanian, Katti, Sebe,
      Kankanhalli, & Chua, 2010). The results show the importance of rarity-based and
      both external and internal contrast-based saliency in fixation prediction.
      Moreover, the comparison with state-of-the-art computational models for visual
      saliency demonstrates the advantage of proto-objects as units of analysis. 

PMID- 24281244
TI  - Change in visual acuity is well correlated with change in image-quality metrics
      for both normal and keratoconic wavefront errors.
AB  - We determined the degree to which change in visual acuity (VA) correlates with
      change in optical quality using image-quality (IQ) metrics for both normal and
      keratoconic wavefront errors (WFEs). VA was recorded for five normal subjects
      reading simulated, logMAR acuity charts generated from the scaled WFEs of 15
      normal and seven keratoconic eyes. We examined the correlations over a large
      range of acuity loss (up to 11 lines) and a smaller, more clinically relevant
      range (up to four lines). Nine IQ metrics were well correlated for both ranges.
      Over the smaller range of primary interest, eight were also accurate and precise
      in estimating the variations in logMAR acuity in both normal and keratoconic
      WFEs. The accuracy for these eight best metrics in estimating the mean change in
      logMAR acuity ranged between +/-0.0065 to +/-0.017 logMAR (all less than one
      letter), and the precision ranged between +/-0.10 to +/-0.14 logMAR (all less
      than seven letters). 

PMID- 24281246
TI  - Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal
      barriers.
AB  - Delivering neurotherapeutics to target brain-associated diseases is a major
      challenge. Therefore, we investigated oral delivery of green fluorescence protein
      (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera
      toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant
      cells) to the brain and retinae of triple transgenic Alzheimer's disease (3*TgAD)
      mice, across the blood-brain barriers (BBB) and blood-retinal barriers (BRB).
      Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not
      with GFP alone. Oral delivery of CTB-MBP in healthy and 3*TgAD mice shows
      increased MBP levels in different regions of the brain, crossing intact BBB.
      Thioflavin S-stained amyloid plaque intensity was reduced up to 60% by CTB-MBP
      incubation with human AD and 3*TgAD mice brain sections ex vivo. Amyloid loads
      were reduced in vivo by 70% in hippocampus and cortex brain regions of 3*TgAD
      mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of
      insoluble amyloid beta 42 (Abeta42) to soluble fractions. CTB-MBP oral delivery
      reduced Abeta42 accumulation in retinae and prevented loss of retinal ganglion
      cells in 3*TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by
      17-fold and stabilized it during long-term storage in capsules, facilitating low
      cost oral delivery of therapeutic proteins across the BBB and BRB. 

PMID- 24281247
TI  - Complete resolution of cerebral air embolism secondary to a transbronchial needle
      aspiration.
AB  - Air embolism following transbronchial needle aspiration (TBNA) is extremely rare.
      To date, only 1 case has been described (estimated incidence: 0.02-0.07%). Here,
      a 70-year-old patient developed a left upper-lobe alveolar syndrome with no
      response to well-conducted antibiotic treatments. Conventional bronchoscopy was
      normal, but virtual bronchoscopy showed that the tumor was contiguous to the left
      B3-B4 division. During a second bronchoscopy, a TBNA was performed without
      bleeding, and pathology later revealed primitive lung adenocarcinoma. Immediately
      after the puncture, an epileptic seizure occurred with right rotation of the head
      and a tonic seizure of the left arm followed by left hemiplegia. A brain CT scan
      performed almost immediately showed no abnormalities and a chest radiography did
      not show any pleural or mediastinal aeric image. A few hours later, clonic
      seizures occurred and brain MRI showed lesions compatible with air embolisms
      (right gyral cortical location). Several hyperbaric therapy sessions successfully
      cured the neurological deficit. Despite its rarity, each practitioner of TBNA has
      to be aware of this side effect and its early treatment. The mechanism of such
      accidents remains unclear, but probably involves high bronchial pressure and
      venous trauma. (c) 2013 S. Karger AG, Basel. 

PMID- 24281245
TI  - Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal
      activity.
AB  - The CNS is endowed with an elaborated response repertoire termed
      'neuroinflammation', which enables it to cope with pathogens, toxins, traumata
      and degeneration. On the basis of recent publications, we deduce that
      orchestrated actions of immune cells, vascular cells and neurons that constitute
      neuroinflammation are not only provoked by pathological conditions but can also
      be induced by increased neuronal activity. We suggest that the technical term
      'neurogenic neuroinflammation' should be used for inflammatory reactions in the
      CNS in response to neuronal activity. We believe that neurogenic neuro
      inflammation maintains homeostasis to enable the CNS to cope with enhanced
      metabolic demands and increases the computational power and plasticity of CNS
      neuronal networks. However, neurogenic neuroinflammation may also become
      maladaptive and aggravate the outcomes of pain, stress and epilepsy. 

PMID- 24281250
TI  - Cost-effectiveness of apixaban compared to warfarin in the management of atrial
      fibrillation in Australia.
AB  - OBJECTIVE: To determine the cost-effectiveness of apixaban versus warfarin in
      patients with atrial fibrillation (AF) with a moderate to severe risk of stroke,
      from an Australian government-perspective. METHODS: A decision-analytic Markov
      model was constructed to assess the cost-effectiveness of apixaban versus
      warfarin, based on data from the Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in AF (ARISTOTLE) trial. The model comprised five health
      states: 'Alive, no major bleeding or stroke', 'Alive, no major bleeding, post
      stroke/systemic embolism', 'Alive, post major bleeding, no stroke', 'Alive, post
      major bleeding and stroke' and 'Dead'. Disease cost data was derived from the
      North-East Melbourne Stroke Incidence Study and the Australian Refined Diagnose
      Related Groups. Costs of medications were based on data from the Pharmaceutical
      Benefit Scheme. Utility data was derived from published sources, and an annual
      discount rate of 5% was applied to costs and benefits. The main outcome of
      interest was incremental cost-effectiveness ratios per life year gained (LYG) and
      quality adjusted life years (QALYs) gained. RESULTS: Over 20 years, in the sample
      of 1000 subjects the model predicted that compared to warfarin, apixaban led to a
      (discounted) of 0.33 LYG and 0.31 QALYs gained, at a net cost of $4,308 per
      person. These equated to ICERs of $AUD12, 914 per LYG and $AUD13, 679 per QALY
      gained. Probabilistic sensitivity analysis demonstrated that apixaban was cost
      effective at 99.0% probability using willingness to pay thresholds of $AUD45 000
      per LYG and QALY. CONCLUSION: Compared to warfarin, apixaban is likely to
      represent a cost-effective means of preventing stroke-related morbidity and
      mortality in patients with AF.

PMID- 24281248
TI  - Impacts of the apoptosis inhibitor of macrophage (AIM) on obesity-associated
      inflammatory diseases.
AB  - Obesity is associated with various metabolic and cardiovascular diseases caused
      by chronic, low-grade inflammation that is initially observed in obese adipose
      tissue. In addition, many etiological studies in humans have shown a strong
      correlation between obesity and inflammatory autoimmune diseases. In this review,
      we focus on the involvement of apoptosis inhibitor of macrophage (AIM), a
      macrophage-derived blood protein, in both types of immune response. Through
      differential mechanisms, AIM thereby plays key roles in the pathogenesis of
      atherosclerosis, metabolic diseases, and obesity-associated autoimmune diseases.
      Thus, the regulation of blood AIM levels or AIM function has the potential to
      serve as a next-generation therapy against these inflammatory diseases brought
      about by modern lifestyle. 

PMID- 24281251
TI  - Increased cardiovascular mortality associated with gout: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Hyperuricaemia, the biochemical precursor to gout, has been shown to
      be an independent risk factor for mortality from cardiovascular disease (CVD),
      although studies examining the clinical phenomenon of gout and risk of CVD
      mortality report conflicting results. This study aimed to produce a pooled
      estimate of risk of mortality from cardiovascular disease in patients with gout.
      DESIGN: Systematic review and meta-analysis. METHODS: Electronic bibliographic
      databases were searched from inception to November 2012, with results reviewed by
      two independent reviewers. Studies were included if they reported data on CVD
      mortality in adults with gout who were free of CVD at time of entry into the
      study. Pooled hazard ratios (HRs) for this association were calculated both
      unadjusted and adjusted for traditional vascular risk factors. RESULTS: Six
      papers, including 223,448 patients, were eligible for inclusion (all (CVD)
      mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial
      infarction mortality n = 3). Gout was associated with an excess risk of CVD
      mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17-1.84)) and CHD
      mortality (unadjusted HR 1.59, 95% CI 1.25-1.94)). After adjusting for
      traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29,
      95% CI 1.14-1.44) and CHD mortality (HR 1.42, 95% CI 1.22-1.63) remained
      statistically significant, but none of the studies reported a significant
      association with myocardial infarction. CONCLUSIONS: Gout increases the risk of
      mortality from CVD and CHD, but not myocardial infarction, independently of
      vascular risk factors.

PMID- 24281252
TI  - Incidence, predictors, and outcomes of failed primary percutaneous coronary
      intervention: a 10-year contemporary experience.
AB  - BACKGROUND: Limited contemporary data exist regarding the incidence, predictors,
      and outcomes of failure of primary percutaneous coronary intervention (PCI) in
      the treatment of ST-segment elevation myocardial infarction (STEMI). MATERIALS
      AND METHODS: In this registry-based retrospective cohort study, all consecutive
      unselected patients (n=1725) who were hospitalized for STEMI and underwent
      primary PCI from January 2001 to December 2010 were included. PCI failure was
      defined as a final diameter stenosis greater than 30% or postdilatation
      Thrombolysis in Myocardial Infarction (TIMI) flow grade of 2 or less. We examined
      the predictors and survival among patients who failed primary PCI. RESULTS: The
      overall PCI failure rate was 5.4% (94 of 1725 procedures). After adjusting for
      prespecified baseline characteristics, independent predictors of PCI failure
      included age greater than 65 years (P=0.02), procedure date between 2001 and 2005
      (P=0.05), night-time PCI (P=0.008), calcific lesion (P=0.008), and lower
      preprocedural TIMI flow grade (P=0.006). Failed PCI was associated with a 1-year
      mortality rate of 22% as compared with 4.2% in the successful PCI group
      (P<0.001). Conservative medical management was preferred in the majority of
      patients with failed PCI (n=78, 83%). Patients who underwent emergent surgery
      (n=11), conservative management (n=78), and redo PCI (n=5) experienced 30-day
      mortality rates of 27, 16, and 0%, respectively. CONCLUSION: Primary PCI failure
      in the setting of STEMI is not rare. It is associated with high-risk patient
      related and angiographic-related characteristics. Primary PCI failure is
      associated with early and late mortality.

PMID- 24281254
TI  - Effect of the structural difference between Bax-alpha5 and Bcl-xL-alpha5 on their
      interactions with lipid bilayers.
AB  - Bax-alpha5 and Bcl-xL-alpha5, which are shorter versions of apoptosis-regulating
      proteins Bax and Bcl-xL, were simulated with lipid bilayers composed of pure
      dioleoylglycerophosphocholine (DOPC) lipids or a mixture of DOPCs and
      cholesterols. Starting with the initial peptide position near the bilayer
      surface, both Bax-alpha5 and Bcl-xL-alpha5 bind to the bilayer because of their
      charge interactions with lipid head groups. After binding to the bilayer surface,
      Bax-alpha5 inserts into the pure DOPC bilayer, but not into the DOPC-cholesterol
      bilayer, showing the effect of cholesterols on the peptide-bilayer interaction.
      Despite the similar peptide structure, Bcl-xL-alpha5 does not insert into the
      bilayer, in contrast to the interaction of Bax-alpha5 with the bilayer. Bcl-xL
      alpha5 predominantly has the random-coil structure in both aqueous and membrane
      environments, while Bax-alpha5 shows a higher extent of alpha-helical structure
      in the bilayer than in water, in quantitative agreement with experiment. In
      particular, although Bax-alpha5 and Bcl-xL-alpha5 have the same extent of the
      electrostatic interaction with lipid head groups, Bax-alpha5 has stronger
      hydrophobic interaction with lipid tails than does Bcl-xL-alpha5. These indicate
      that Bax-alpha5 retains alpha-helical structure, where hydrophobic residues on
      one side of the alpha-helix interact with lipid tails and thus can easily attract
      the peptide into the lipid-tail region, while Bcl-xL-alpha5 forms a random coil
      that tends to spread on the bilayer surface and thus has weaker hydrophobic
      interaction with lipid tails. Our findings help explain the experimental
      observation that showed that Bax-alpha5 disorders lipids and induces pore
      formation, but Bcl-xL-alpha5 does not. 

PMID- 24281253
TI  - Silencing of RB1 and RB2/P130 during adipogenesis of bone marrow stromal cells
      results in dysregulated differentiation.
AB  - Bone marrow adipose tissue (BMAT) is different from fat found elsewhere in the
      body, and only recently have some of its functions been investigated. BMAT may
      regulate bone marrow stem cell niche and plays a role in energy storage and
      thermogenesis. BMAT may be involved also in obesity and osteoporosis onset. Given
      the paramount functions of BMAT, we decided to better clarify the human bone
      marrow adipogenesis by analyzing the role of the retinoblastoma gene family,
      which are key players in cell cycle regulation. Our data provide evidence that
      the inactivation of RB1 or RB2/P130 in uncommitted bone marrow stromal cells
      (BMSC) facilitates the first steps of adipogenesis. In cultures with silenced RB1
      or RB2/P130, we observed an increase of clones with adipogenic potential and a
      higher percentage of cells accumulating lipid droplets. Nevertheless, the absence
      of RB1 or RB2/P130 impaired the terminal adipocyte differentiation and gave rise
      to dysregulated adipose cells, with alteration in lipid uptake and release. For
      the first time, we evidenced that RB2/P130 plays a role in bone marrow
      adipogenesis. Our data suggest that while the inactivation of retinoblastoma
      proteins may delay the onset of last cell division and allow more BMSC to be
      committed to adipocyte, it did not allow a permanent cell cycle exit, which is a
      prerequisite for adipocyte terminal maturation. 

PMID- 24281255
TI  - The Use of California Sagebrush (Artemisia californica) Liniment to Control Pain.
AB  - The incidence of arthritis is increasing every year, as does the need for pain
      medication. The current work reviews an American Indian liniment that is
      traditionally used for pain therapy. The chemistry, therapeutic use and safety of
      the liniment are reviewed. The liniment contains monoterpenoids, sesquiterpenes,
      flavonoids, alkaloids and other compounds. 

PMID- 24281256
TI  - Cell-penetrating recombinant peptides for potential use in agricultural pest
      control applications.
AB  - Several important areas of interest intersect in a class of peptides
      characterized by their highly cationic and partly hydrophobic structure. These
      molecules have been called cell-penetrating peptides (CPPs) because they possess
      the ability to translocate across cell membranes. This ability makes these
      peptides attractive candidates for delivery of therapeutic compounds, especially
      to the interior of cells. Compounds with characteristics similar to CPPs and
      that, in addition, have antimicrobial properties are being investigated as
      antibiotics with a reduced risk of causing resistance. These CPP-like membrane
      acting antimicrobial peptides (MAMPs) are alpha-helical amphipathic peptides that
      interact with and perturb cell membranes to produce their antimicrobial effects.
      One source of MAMPs is spider venom. Because these compounds are toxic to
      insects, they also show promise for development as biological agents for control
      of insecticide-resistant agricultural pests. Spider venom is a potential source
      of novel insect-specific peptide toxins. One example is the small amphipathic
      alpha-helical peptide lycotoxin-1 (Lyt-1 or LCTX) from the wolf spider (Lycosa
      carolinensis). One side of the alpha-helix has mostly hydrophilic and the other
      mainly hydrophobic amino acid residues. The positive charge of the hydrophilic
      side interacts with negatively charged prokaryotic membranes and the hydrophobic
      side associates with the membrane lipid bilayer to permeabilize it. Because the
      surface of the exoskeleton, or cuticle, of an insect is highly hydrophobic, to
      repel water and dirt, it would be expected that amphipathic compounds could
      permeabilize it. Mutagenized lycotoxin 1 peptides were produced and expressed in
      yeast cultures that were fed to fall armyworm (Spodoptera frugiperda) larvae to
      identify the most lethal mutants. Transgenic expression of spider venom toxins
      such as lycotoxin-1 in plants could provide durable insect resistance. 

PMID- 24281257
TI  - Statistical estimation of the protein-ligand binding free energy based on direct
      protein-ligand interaction obtained by molecular dynamics simulation.
AB  - We have developed a method for estimating protein-ligand binding free energy (DG)
      based on the direct protein-ligand interaction obtained by a molecular dynamics
      simulation. Using this method, we estimated the DG value statistically by the
      average values of the van der Waals and electrostatic interactions between each
      amino acid of the target protein and the ligand molecule. In addition, we
      introduced fluctuations in the accessible surface area (ASA) and dihedral angles
      of the protein-ligand complex system as the entropy terms of the DG estimation.
      The present method included the fluctuation term of structural change of the
      protein and the effective dielectric constant. We applied this method to 34
      protein-ligand complex structures. As a result, the correlation coefficient
      between the experimental and calculated DG values was 0.81, and the average error
      of DG was 1.2 kcal/mol with the use of the fixed parameters. These results were
      obtained from a 2 nsec molecular dynamics simulation. 

PMID- 24281258
TI  - Design, synthesis and hydrolytic behavior of mutual prodrugs of NSAIDs with
      gabapentin using glycol spacers.
AB  - The free &ndash;COOH present in NSAIDs is thought to be responsible for the GI
      irritation associated with all traditional NSAIDs. Exploitation of mutual
      prodrugs is an approach wherein the NSAID is covalently bounded to a second
      pharmacologically active carrier/drug with the ultimate aim of reducing the
      gastric irritation. In this study some NSAIDs were conjugated with gabapentin via
      ester bonds using glycol spacers with the expectation of reducing gastric adverse
      effects and obtaining synergistic analgesic effects. The kinetics of ester
      hydrolysis were studied in two different non enzymatic buffer solutions at pH 1.2
      and 7.4, as well as in 80% human plasma using HPLC with chloroform -methanol as
      mobile phase. Compounds 9a&ndash;c with ethylene glycol spacers showed
      significant stability at buffer solutions with half lives ranging from about
      8&ndash;25 h, while the underwent a reasonable plasma hydrolysis (49%&ndash;88%)
      in 2 h. Compound 9d with a propylene glycol spacer shows a higher rate of
      enzymatic hydrolysis than the corresponding ethylene glycol compound 9c. The
      result of compounds 9a-c indicate that these compounds may be stable during their
      passage through the GIT until reaching the blood circulation. 

PMID- 24281259
TI  - Intranasal delivery of camptothecin-loaded tat-modified nanomicells for treatment
      of intracranial brain tumors.
AB  - The blood-brain barrier is a substantial obstacle for delivering anticancer
      agents to brain tumors, and new strategies for bypassing it are sorely needed for
      brain tumor therapy. Intranasal delivery provides a practical, noninvasive method
      for delivering therapeutic agents to the brain. Intranasal application of nano
      sized micelles that have been modified with Tat peptide facilitates brain
      delivery of fluorescent model materials. In this study, we evaluated a nose-to
      brain delivery system for brain tumor therapy. We nasally administered the anti
      tumor drug camptothecin (CPT) in solution and in methoxy poly(ethylene glycol)
      (MPEG)/poly(e-caprolactone) (PCL) amphiphilic block copolymers (MPEG-PCL) and
      cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat) MPEG-PCL
      Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity
      against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat
      micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL
      Tat didn't show any cytotoxicity, even at high concentrations (2 mmol/mL). CPT
      loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats.
      These results indicate that intranasal delivery of anti-cancer drugs with cell
      penetrating peptide-modified nanomicelles might be an effective therapy for brain
      tumors. 

PMID- 24281260
TI  - Norethindrone acetate in the medical management of adenomyosis.
AB  - The role of norethindrone acetate (NA) in the management of adenomyosis was
      evaluated with a retrospective chart review of 28 premenopausal women between 27
      49 years of age presenting with moderate to severe pelvic pain and bleeding.
      Bleeding and dysmenorrhea scores were analyzed using paired T-tests. There was
      significant improvement of both dysmenorrhea and bleeding after treatment. Age
      showed no correlation with dysmenorrhea or bleeding. Low dose NA could be
      considered an effective, well-tolerated and inexpensive medical alternative to
      surgery for treating symptomatic adenomyosis. Large multicentric studies may help
      validate our findings. 

PMID- 24281262
TI  - PDMS lab-on-a-chip fabrication using 3D printed templates.
AB  - The fabrication of conventional PDMS on glass lab-on-a-chip (LOC) devices, using
      templates printed with a commercial (2299 US$) micro-stereo lithography 3D
      printer, is demonstrated. Printed templates replace clean room and
      photolithographic fabrication resources and deliver resolutions of 50 MUm, and up
      to 10 MUm in localized hindrances, whereas the templates are smooth enough to
      allow direct transfer and proper sealing to glass substrates. 3D printed
      templates accommodate multiple thicknesses, from 50 MUm up to several mm within
      the same template, with no additional processing cost or effort. This capability
      is exploited to integrate silicone tubing easily, to improve micromixer
      performance and to produce multilevel fluidics with simple access to independent
      functional surfaces, which is illustrated by time-resolved glucose detection. The
      templates are reusable, can be fabricated in under 20 min, with an average cost
      of 0.48 US$, which promotes broader access to established LOC configurations with
      minimal fabrication requirements, relieves LOC fabrication from design skills and
      provides a versatile LOC development platform. 

PMID- 24281261
TI  - Advances in drug design based on the amino Acid approach: taurine analogues for
      the treatment of CNS diseases.
AB  - Amino acids are well known to be an important class of compounds for the
      maintenance of body homeostasis and their deficit, even for the polar neuroactive
      aminoacids, can be controlled by supplementation. However, for the amino acid
      taurine (2-aminoethanesulfonic acid) this is not true. Due its special
      physicochemical properties, taurine is unable to cross the blood-brain barrier.
      In addition of injured taurine transport systems under pathological conditions,
      CNS supplementation of taurine is almost null. Taurine is a potent antioxidant
      and anti-inflammatory semi-essential amino acid extensively involved in
      neurological activities, acting as neurotrophic factor, binding to GABA A/glycine
      receptors and blocking the excitotoxicity glutamate-induced pathway leading to be
      a neuroprotective effect and neuromodulation. Taurine deficits have been
      implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy
      and in the damage of retinal neurons. This review describes the CNS physiological
      functions of taurine and the development of new derivatives based on its
      structure useful in CNS disease treatment. 

PMID- 24281263
TI  - Ex utero intrapartum treatment to resection of a bronchogenic cyst causing airway
      compression.
AB  - We present a case report of a 28-year-old primigravida with a singleton pregnancy
      complicated by a fetal bronchogenic cyst compressing the left mainstem bronchus
      with resultant hyperinflation of the entire left lung and rightward mediastinal
      shift. An ex utero intrapartum treatment to resection of the fetal bronchogenic
      cyst via a fetal thoracotomy was performed at 36 weeks' gestational age,
      circumventing a potentially complicated neonatal airway emergency at birth.

PMID- 24281264
TI  - Suboptimal initiation of home hemodialysis: determinants and clinical outcomes.
AB  - BACKGROUND/AIMS: Suboptimal initiation of conventional hemodialysis is associated
      with poor clinical outcomes. In this study, we aimed to ascertain the
      determinants and adverse events associated with suboptimal starts in home
      hemodialysis (HHD). METHODS: We conducted a retrospective cohort study including
      consecutive incident HHD patients from January 1996 to December 2011. All
      patients had HHD as their first renal replacement therapy or returned to HHD
      after kidney transplantation. A suboptimal start was defined by dialysis
      initiation as an inpatient or with a central venous catheter. The primary outcome
      was time to first hospitalization, technique failure or death. Secondary outcomes
      included hospitalization rate, hospital days and determinants of suboptimal
      starts. Suboptimal starts were further categorized as unavoidable as adjudicated
      by two independent observers with prespecified criteria. RESULTS: Among 95
      incident HHD patients, 44 (46%) and 51 (54%) had optimal and suboptimal starts,
      respectively. A suboptimal start was associated with a shorter time to the
      primary outcome (log-rank p < 0.001). In a multivariable Cox proportional hazards
      model, the hazard ratio for the composite outcome (comparing suboptimal to
      optimal starts) was 2.94 (95% confidence interval, CI, 1.49-5.78, p = 0.002).
      Transplantation clinic follow-up (OR 3.18, 95% CI 1.15-8.79) and the Charlson
      comorbidity index (OR 1.47, 95% CI 1.09-1.97) were associated with higher odds of
      suboptimal start. CONCLUSION: Suboptimal initiation of HHD is associated with
      adverse clinical events including early hospitalization. Given the high
      proportion of suboptimal starts in patients returning from transplantation,
      better incorporation of dialysis planning and renal replacement therapy education
      is warranted.

PMID- 24281266
TI  - Predictors of outcome after mechanical thrombectomy for anterior circulation
      large vessel occlusion in patients aged >=80 years.
AB  - BACKGROUND: There is uncertainty about the role of endovascular recanalization
      procedures for the treatment of acute ischemic stroke in patients aged >=80
      years. Therefore, careful patient selection is mandatory. Our aim was to find
      valid predictors of clinical outcome after mechanical thrombectomy (mTE) based on
      the sparse information available in the emergency setting. METHODS: We included
      consecutive patients aged >=80 years treated by mTE for anterior circulation
      thromboembolic vessel occlusion in our department between January 2008 and
      January 2013. Successful recanalization was defined as a thrombolysis in cerebral
      infarction (TICI) score of 2b or 3. The rates of parenchymal hemorrhage types I
      (PHI) and II (PHII) according to the ECASS definition and the rate of focal and
      diffuse subarachnoid hemorrhage (SAH) were reported. A modified Ranking scale
      (mRS) score of 0-2 at 90 days was defined as a favorable outcome. We evaluated
      the influence of gender, smoking habits, atrial fibrillation, diabetes,
      hypertension, hyperlipidemia, coronary artery and peripheral artery disease,
      National Institutes of Health Stroke Scale (NIHSS) score, Totaled Health Risks in
      Vascular Events (THRIVE) score, Alberta Stroke Program Early CT Score (ASPECTS),
      and duration of symptoms on favorable outcome. Significant predictors were then
      included in a stepwise logistic regression analysis. Odds ratios (OR), 95%
      confidence intervals (CI), and receiver operating characteristics (ROC) curves
      were calculated. p < 0.05 was considered statistically significant. RESULTS: In
      the defined period, we treated 109 patients aged >=80 years with 116 occluded
      anterior circulation target vessels. Successful recanalization was achieved in
      87.9% of the targets. The rates of PHI, PHII, and focal and diffuse SAH were 6.4,
      5.5, 12.8, and 7.3%, with an overlap between PH and SAH. The combined rate of
      PHII and/or diffuse SAH was 9.2%. Despite good recanalization rates and
      reasonable rates of hemorrhage, only 19 patients (17.4%) were functionally
      independent at 90 days. An additional 12 patients (11.0%) suffered from moderate
      disability (mRS score 3), 26 (23.9%) were severely disabled (mRS score 4-5) and
      52 (47.7%) were deceased. NIHSS, ASPECTS, and THRIVE scores significantly
      predicted a favorable outcome. Stepwise logistic regression identified NIHSS (OR
      0.89; 95% CI 0.82-0.96; p = 0.009) and ASPECTS (OR 2.27; 95% CI 1.28-4.02; p =
      0.005) as independent predictors. The ROC area was 0.81. CONCLUSION: ASPECTS and
      NIHSS were independent predictors of a favorable outcome in patients aged >=80
      years after mTE for anterior circulation large vessel occlusion and may support
      decision making with regard to the treatment modality. Since the chances of
      gaining functional independence are limited, careful consideration of each
      individual case is mandatory. Further studies comparing endovascular and standard
      treatment in octogenarians are warranted.

PMID- 24281265
TI  - Chaperone-mediated autophagy: roles in disease and aging.
AB  - This review focuses on chaperone-mediated autophagy (CMA), one of the proteolytic
      systems that contributes to degradation of intracellular proteins in lysosomes.
      CMA substrate proteins are selectively targeted to lysosomes and translocated
      into the lysosomal lumen through the coordinated action of chaperones located at
      both sides of the membrane and a dedicated protein translocation complex. The
      selectivity of CMA permits timed degradation of specific proteins with regulatory
      purposes supporting a modulatory role for CMA in enzymatic metabolic processes
      and subsets of the cellular transcriptional program. In addition, CMA contributes
      to cellular quality control through the removal of damaged or malfunctioning
      proteins. Here, we describe recent advances in the understanding of the molecular
      dynamics, regulation and physiology of CMA, and discuss the evidence in support
      of the contribution of CMA dysfunction to severe human disorders such as
      neurodegeneration and cancer. 

PMID- 24281270
TI  - Octoxy capped Si nanoparticles synthesized by homogeneous reduction of SiCl4 with
      crown ether alkalide.
AB  - Blue-green luminescent octoxy capped Si nanoparticles were synthesized via
      homogeneous reduction of SiCl4 with the crown ether alkalide K(+)(15-crown-5)2K(
      ) in tetrahydrofuran. The Si nanoparticles were characterized with respect to
      size, crystal structure, morphology, surface termination, optical properties and
      stability. Si diamond structure nanoparticles with narrow size distributions, and
      average diameters ranging from 3 to 7 nm were obtained. A finite-size effect on
      the lattice dimensions was observed, in the form of an expansion of the [220]
      lattice planes of smaller Si nanoparticles. The concentration of SiCl4 was found
      to be the most important parameter governing the particle size and size
      distribution. The octoxy capped particles were stable under an ambient atmosphere
      for at least one month, but exposure to water made them prone to oxidation. An
      average radiative recombination lifetime of 8.8 ns was measured for the blue
      green luminescence. The luminescence appears to originate from surface defects,
      rather than from quantum confinement. 

PMID- 24281269
TI  - Current knowledge on tumour induction by computed tomography should be carefully
      used.
AB  - Risks associated to ionising radiation from medical imaging techniques have
      focused the attention of the medical society and general population. This risk is
      aimed to determine the probability that a tumour is induced as a result of a
      computed tomography (CT) examination since it makes nowadays the biggest
      contribution to the collective dose. Several models of cancer induction have been
      reported in the literature, with diametrically different implications. This
      article reviews those models, focusing on the ones used by the scientific
      community to estimate CT detriments. Current estimates of the probability that a
      CT examination induces cancer are reported, highlighting its low magnitude (near
      the background level) and large sources of uncertainty. From this objective
      review, it is concluded that epidemiological data with more accurate dosimetric
      estimates are needed. Prediction of the number of tumours that will be induced in
      population exposed to ionising radiation should be avoided or, if given, it
      should be accompanied by a realistic evaluation of its uncertainty and of the
      advantages of CTs. Otherwise they may have a negative impact in both the medical
      community and the patients. Reducing doses even more is not justified if that
      compromises clinical image quality in a necessary investigation. Key Points *
      Predictions of radiation-induced cancer should be discussed alongside benefits of
      imaging. * Estimates of induced cancers have noticeable uncertainties that should
      always be highlighted. * There is controversy about the acceptance of the linear
      no-threshold model. * Estimated extra risks of cancer are close to the background
      level. * Patients should not be alarmed by potential cancer induction by CT
      examinations. 

PMID- 24281271
TI  - Caregiver's perceptions of the relationship of pain to behavioral and psychiatric
      symptoms in older community-residing adults with dementia.
AB  - OBJECTIVES: Pain is underrecognized and undermanaged in older adults with
      dementia. Because dementia patients have a diminished capacity to communicate
      discomfort, untreated pain may be expressed in the form of behavioral and
      psychiatric symptoms. The goal of the present study was to examine the
      relationship between pain and behavioral and psychiatric symptoms of dementia in
      community-residing older adults from the perspective of the family caregiver.
      MATERIALS AND METHODS: Dyads composed of 272 dementia patients, and their family
      caregivers were assessed to determine dementia patient's mental status; family
      caregiver's assessment of care recipient's pain, functional dependence, and
      number of behavioral symptoms; analgesic use; and demographic information.
      RESULTS: Hierarchical multiple regression analysis controlling for age, marital
      status, race, functional disability, and analgesic use showed that pain explained
      a small but significant percent of variance in the number of behavioral symptoms
      (3%, P<0.001). Pain had a stronger influence on the number of behavioral and
      psychiatric symptoms of dementia among those with severe cognitive impairment
      (F1,69=11.75, P<0.001) compared with those with low to moderate cognitive
      impairment (F1,199=4.543, P=0.034.). DISCUSSION: The findings indicate that pain
      is a risk factor for behavioral symptoms in individuals with dementia and suggest
      that pain is a more significant predictor of behavior for individuals with severe
      dementia, compared with those with mild/moderate stage dementia. These results
      reinforce the importance of proper pain assessment and its management as part of
      dementia care planning.

PMID- 24281272
TI  - The role of anger in psychosocial subgrouping for patients with low back pain.
AB  - BACKGROUND: Low back pain (LBP) is a common and costly condition that often
      becomes chronic if not properly addressed. Recent research has shown that
      psychosocial symptoms can complicate LBP, necessitating more comprehensive
      screening measures. AIM: The present study investigated the role of psychosocial
      factors, including anger regulation, in pain and disability using a screening
      measure designed for LBP treated with physical therapy. METHODS: One hundred
      three LBP patients initiating physical therapy completed an established screening
      measure to assess risk for developing chronic pain, and psychosocial measures
      assessing anger, depression, anxiety, fear-avoidance, and pain-catastrophizing
      before and after 4 weeks of treatment. Dependent variables were pain intensity,
      physical impairment, and patient-reported disability. Risk subgrouping based on
      anger and other psychosocial measures was examined using established screening
      methods and through using an empirical statistical approach. RESULTS: Analyses
      revealed that risk subgroups differed according to corresponding levels of
      negative affect, as opposed to anger alone. General psychosocial distress also
      predicted disability posttreatment, but, interestingly, did not have a strong
      relationship to pain. Subsequent hierarchical agglomerative clustering procedures
      divided patients into overall high-distress and low-distress groups, with follow
      up analyses revealing that the high-distress group had higher baseline measures
      of pain, disability, and impairment. CONCLUSIONS: Findings suggest that anger may
      be part of a generalized negative affect rather than a unique predictor when
      assessing risk for pain and disability in LBP treatment. Continued research in
      the area of screening for psychosocial prognostic indicators in LBP may
      ultimately guide treatment protocols in physical therapy for more comprehensive
      patient care.

PMID- 24281273
TI  - The role of opioid prescription in incident opioid abuse and dependence among
      individuals with chronic noncancer pain: the role of opioid prescription.
AB  - OBJECTIVE: Increasing rates of opioid use disorders (OUDs) (abuse and dependence)
      among patients prescribed opioids are a significant public health concern. We
      investigated the association between exposure to prescription opioids and
      incident OUDs among individuals with a new episode of a chronic noncancer pain
      (CNCP) condition. METHODS: We utilized claims data from the HealthCore Database
      for 2000 to 2005. The dataset included all individuals aged 18 and over with a
      new CNCP episode (no diagnosis in the prior 6 mo), and no opioid use or OUD in
      the prior 6 months (n=568,640). We constructed a single multinomial variable
      describing prescription on opioid days supply (none, acute, and chronic) and
      average daily dose (none, low dose, medium dose, and high dose), and examined the
      association between this variable and an incident OUD diagnosis. RESULTS:
      Patients with CNCP prescribed opioids had significantly higher rates of OUDs
      compared with those not prescribed opioids. Effects varied by average daily dose
      and days supply: low dose, acute (odds ratio [OR]=3.03; 95% confidence interval
      [CI], 2.32, 3.95); low dose, chronic (OR=14.92; 95% CI, 10.38, 21.46); medium
      dose, acute (OR=2.80; 95% CI, 2.12, 3.71); medium dose, chronic (OR=28.69; 95%
      CI, 20.02, 41.13); high dose, acute (OR=3.10; 95% CI, 1.67, 5.77); and high dose,
      chronic (OR=122.45; 95% CI, 72.79, 205.99). CONCLUSIONS: Among individuals with a
      new CNCP episode, prescription opioid exposure was a strong risk factor for
      incident OUDs; magnitudes of effects were large. Duration of opioid therapy was
      more important than daily dose in determining OUD risk.

PMID- 24281274
TI  - Spousal mindfulness and social support in couples with chronic pain.
AB  - OBJECTIVES: Existing research has reported the correlation between patients'
      psychological flexibility, of which mindfulness is a component, and their
      perceptions of the spouses' support provision. It is quite likely that spouses'
      mindfulness, in particular certain aspects of mindfulness, is also related to the
      support they provide to patients. The current study examined this issue.
      MATERIALS AND METHODS: The sample included 51 couples in which 1 partner had
      chronic pain. Patients and their spouses each completed a questionnaire that
      assessed 3 facets of their own mindfulness (ie, nonreactivity, acting with
      awareness, nonjudging). In addition, patients reported on their pain-related
      psychological flexibility, marital satisfaction, and perceptions of spousal
      support. RESULTS: Only 1 facet of patients' mindfulness (ie, nonreactivity) was
      related to their perceptions of their spouses as being emotionally responsive to
      them. Spouses' nonjudging and nonreactivity were negatively correlated with
      punishing spouse responses. In addition, spouses' acting with awareness was
      positively correlated with patients' reports of perceived partner responsiveness
      and instrumental support and negatively correlated with patients' reports of
      punishing spouse responses, often over and above the contribution of patients'
      own mindfulness or pain-related psychological flexibility. DISCUSSION: Spouses'
      mindfulness, especially as it pertains to acting with awareness, was most
      consistently associated with patient perceptions of spousal support. These
      findings suggest that acting with awareness should be examined further including
      the possible contributions this type of mindfulness may make to healthy
      relationship behaviors in the context of pain.

PMID- 24281275
TI  - Efficacy of postoperative continuous wound infiltration with local anesthesia
      after open hepatectomy.
AB  - OBJECTIVES: Local anesthetic wound infiltration is widely used as an effective
      adjunct during multimodal postoperative pain management. The aim of this study
      was to evaluate the effectiveness of continuous wound infusion of ropivacaine in
      postoperative pain relief, opioid sparing, incidence of nausea and vomiting, and
      bowel and liver function improvement in patients undergoing open hepatectomy.
      METHODS: Forty patients undergoing open hepatectomy were enrolled in this
      prospective, randomized, double-blinded, placebo-controlled trial. Patients were
      divided into 2 groups: the 0.9% saline continuous infusion group (the control
      group; n=20) and the ropivacaine continuous infusion group (the Ropi group;
      n=20). Outcomes measured postoperatively were pain score at rest and on movement,
      sufentanil consumption, incidence of nausea and vomiting, and sedation score
      across 48 postoperative hours. Time to bowel recovery, liver function change,
      mean length of hospitalization, patient satisfaction, and other data after 48
      postoperative hours were collected until hospital discharge. RESULTS: Pain scores
      at rest were lower for the ropivacaine group and reached significance after 8 and
      16 hours (P<0.01). Sufentanil consumption (41.50+/-21.80 vs. 89.70+/-35.22 MUg;
      P<0.01) after 48 hours, time to bowel recovery (1.80+/-0.70 vs. 3.15+/-1.04 d;
      P<0.01), incidence of nausea and vomiting (1.75+/-0.72 vs. 2.40+/-0.68; P<0.05),
      and mean length of hospitalization (5.6+/-2.44 vs. 7.35+/-2.85 d; P<0.01) were
      significantly reduced, and the sedation score and liver function change were also
      comparable between the 2 groups. There was no difference with respect to pain
      scores on movement, nor with respect to patient satisfaction. CONCLUSIONS:
      Surgical wound infusion with ropivacaine after hepatectomy can improve pain
      relief at rest and accelerate recovery and discharge.

PMID- 24281276
TI  - The subjective psychoactive effects of oral dronabinol studied in a randomized,
      controlled crossover clinical trial for pain.
AB  - BACKGROUND: Many cannabinoid medications are approved in North America or in
      phase III trials, such as dronabinol, nabilone, or nabiximols. Little is known
      about their subjective psychoactive effects when used for pain management. We
      hypothesized that when used for pain, dronabinol has psychoactive effects in a
      dose-response relationship, whose peak effects are comparable with smoking
      marijuana. METHODS: This was a randomized controlled trial of single dose
      placebo, 10 or 20 mg dronabinol in 30 chronic noncancer pain patients taking
      opioids and not using marijuana. Participants completed the Addiction Research
      Center Inventory (ARCI) hourly for 8 hours during 3 monitored sessions.
      Comparison sample was the ARCI ratings in participants with no pain (N=20),
      monitored every 30 minutes after smoking a 1.99% THC (low) and a 3.51% (high
      strength) marijuana cigarette. RESULTS: The 10 and 20 mg dronabinol doses had
      significantly elevated scores over time on 4/5 subscales versus placebo (P<0.05).
      Average daily morphine use, total pain relief (TOTPAR), age, sex, and baseline
      pain level were not significant covariates. ARCI peak effects at 2 hours were
      similar to peak effects of smoked marijuana at 30 minutes (P=0.80, 10 mg=low
      strength, 20 mg=high strength). CONCLUSIONS: In pain patients, oral dronabinol
      has similar psychoactive effects to smoking marijuana. This risk must be
      considered in any decision to prescribe cannabinoid medications for pain.

PMID- 24281277
TI  - The concurrent validity of brief screening questions for anxiety, depression,
      social isolation, catastrophization, and fear of movement in people with low back
      pain.
AB  - OBJECTIVES: The aim of this study was to (1) test the concurrent validity of
      brief screening questions for 5 psychosocial constructs (anxiety, depression,
      social isolation, catastrophization, and fear of movement) and (2) translate into
      Danish and validate those screening questions. MATERIALS AND METHODS: Data were
      collected from 5 cross-sectional samples (total n=1105) of people seeking care
      for low back pain in Australian primary care settings and a Danish secondary care
      hospital. The responses to English and Danish-translated versions of 1-item or 2
      item screening questions were compared with those of validated full-length
      questionnaires. RESULTS: Compared with anxiety, depression, and social isolation
      scores from full-length questionnaires, screening questionnaire responses
      demonstrated: a correlation of 0.62 to 0.83, overall accuracy of 78% to 91%,
      sensitivity of 70% to 82%, specificity of 75% to 95%, positive likelihood ratios
      of 3.3 to 13.9, and negative likelihood ratios of 0.21 to 0.33. For
      catastrophization and fear of movement, the results demonstrated: correlation of
      0.89 to 0.95, overall accuracy of 88% to 93%, sensitivity of 78% to 88%,
      specificity of 91% to 96%, positive likelihood ratios of 9.5 to 20.8, and
      negative likelihood ratios of 0.13 to 0.23. DISCUSSION: The concurrent validity
      of these screening questions was comparable to, or better than, alternate
      questions previously reported, and stable across age, sex, pain intensity, pain
      duration, and counties. On the basis of the observed likelihood ratios, all of
      the screening questions provided moderate or strong evidence to rule in or out an
      extreme score on each psychosocial construct. Given the ease of administration of
      these brief screening questions, their prognostic and treatment implications
      should be investigated.

PMID- 24281278
TI  - Trends and regional variation in opioid overdose mortality among Veterans Health
      Administration patients, fiscal year 2001 to 2009.
AB  - OBJECTIVES: Opioid-related mortality has increased in the United States in the
      past decade. The purpose of this study was to examine trends and regional
      variation in opioid prescribing and overdose rates in a national health system,
      the Veterans Health Administration. MATERIALS AND METHODS: Annual cohorts of
      Veterans Health Administration patients were identified on the basis of medical
      records, and overdose mortality was determined from National Death Index records.
      State-level prescribing and overdose rates were mapped to provide information on
      regional variability. RESULTS: There were significant increases between 2001 and
      2009 in the rate of overdoses associated with nonsynthetic opioids (beta=0.53,
      95% confidence interval, 0.35, 0.70) and methadone (beta=0.63, 95% confidence
      interval, 0.37, 0.90) but not synthetic/semisynthetic opioids. State-level
      overdose rates had a moderate correlation with the average proportion of patients
      in that state receiving opioids (r=0.29). DISCUSSION: The present study
      demonstrates that the increases in prescription opioid overdoses observed in the
      general population are also found in the patient population of a national health
      system and provides further evidence of the population-level association between
      trends in opioid prescribing and opioid overdose deaths. There is substantial
      regional variation in both opioid prescribing and opioid-related overdose rates,
      and these data can inform region-specific overdose prevention strategies and
      opioid policy.

PMID- 24281279
TI  - Single-dose intra-articular bupivacaine versus morphine after arthroscopic knee
      surgery: a meta-analysis of randomized-controlled studies.
AB  - OBJECTIVES: This meta-analysis compared the earliest clinical effects of intra
      articular bupivacaine and morphine for pain management following arthroscopic
      knee surgery. MATERIALS AND METHODS: A comprehensive literature search was
      conducted using MEDLINE (1966 to 2013), the Cochrane Central Register of
      Controlled Trials (CENTRAL), Embase, and Google Scholar databases for
      identification of randomized-controlled trials that compared IA bupivacaine and
      morphine for postoperative pain. The relative risk, weighted mean difference
      (WMD), and their corresponding 95% confidence intervals (CI) were calculated
      using RevMan statistical software. RESULTS: Bupivacaine and morphine group had
      similar acute postoperative pain scores (WMD: 0.07; 95% CI, -0.18 to 0.32;
      P=0.60); number of patients requiring supplementary analgesia (relative risk:
      0.74; 95% CI, 0.42 to 1.31; P=0.30) for the trials in this meta-analysis (n=13);
      and side effects (relative risk: 0.63; 95% CI, 0.39 to 1.02, P=0.06). Even
      though, the time to first analgesic request resulted in a significant difference
      (WMD: 66.59; 95% CI, 11.75 to 122.14, P=0.02), this result was not supported by
      the sensitivity analysis. CONCLUSIONS: On the basis of the currently available
      literature, this study failed to demonstrate a significant difference between
      single-dose intra-articular bupivacaine and morphine at the end of the
      arthroscopic knee surgery in terms of pain relief, need for supplementary
      analgesics, times interval before the first request for additional analgesic, and
      short-term side effects. LEVEL OF EVIDENCE: Level II-meta-analysis of Level I and
      II studies.

PMID- 24281280
TI  - Chronic perineal pain: analyses of prognostic factors in pudendal neuralgia.
AB  - OBJECTIVES: To establish the prognostic factors and outcomes of patients with
      pudendal neuralgia (PN). MATERIALS AND METHODS: A total of 51 patients with PN
      treated at the Puerta de Hierro University Hospital of Madrid between January
      2011 and June 2012 were included in this study. Patients were compared in
      relation to pain intensity and response to the first-line treatment of
      neuropathic pain. Univariate and multivariable Cox regression analyses were used.
      RESULTS: The median for patients' age, duration, and intensity of pain evaluated
      by visual analogue scale were 40.9, 3.6, and 7.6 years, respectively. Among 45
      patients, there were 19 good responders to first-line treatment for neuropathic
      pain and 26 nonresponders. The 19 responders measured their improvement at 47%.
      Tramadol was used for nonresponding patients, 30.8% of whom expressed a 35%
      improvement. Analysis of 45 patients with PN demonstrated that the pain intensity
      was associated with dorsal clitoris nerve damage (15.4% vs. 52.2%; P=0.035; odds
      ratio 4.5; 95% confidence interval [CI], 1.11-18.1) and with sensory deficit at
      the S2-S4 dermatome map (57.7% vs. 87%; P=0.05; odds ratio 3.7; 95% CI, 0.80
      16.8). The pain located at the dorsal clitoris nerve was a significant prognostic
      factor for having no response to the first-line treatment of neuropathic pain
      (28% vs. 53%; P=0.033; odds ratio 4.5; 95% CI, 1.06-19.6). DISCUSSION: A mixed
      analgesic ladder for chronic pain showed improvement in 73% of the patients with
      PN. Pain restricted to the dorsal clitoris nerve and small fibers in the S2-S4
      dermatome were classified as bad prognostic factors. A longer duration of pain
      was also correlated with a worse prognosis.

PMID- 24281281
TI  - Beyond neuropathic pain: gabapentin use in cancer pain and perioperative pain.
AB  - BACKGROUND: Gabapentin (GBP), originally an antiepileptic drug, is more commonly
      used in the treatment of neuropathic pain. In recent years, GBP has been used as
      an adjunct or primary therapy in non-neuropathic pain, most commonly for the
      treatment of perioperative and cancer pain. OBJECTIVES: The aim of this study was
      to conduct a clinical evidence literature review of GBP's use in perioperative
      pain and cancer pain. METHODS: Using PUBMED and OVID Medline databases, keyword
      searches for surgery and cancer in reference to GBP and pain were carried out.
      Nonblinded studies and case reports that did not present a unique finding were
      excluded. Studies that focused only on neuropathic pain were also excluded.
      RESULTS: An initial 142 references focusing on GBP's use in surgical pain and
      cancer pain were identified. Of these, 48 studies were quality of evidence at a
      level of II-2 or higher. DISCUSSION: Although efficacy varies, multiple well
      designed clinical trials have demonstrated reduced pain and analgesic use with
      otolaryngology, orthopedic, mastectomy, and abdominal/pelvic surgical
      perioperative use of GBP, whereas there is limited or no efficacy for
      cardiothoracic surgery. Cancer pain studies have had greater design variability,
      often nonblinded, with pain benefit being mild to moderate, and more efficacious
      with partial neuropathic pain quality. Overall, GBP seems to have significant
      benefit in neuropathic and non-neuropathic pain associated with the perioperative
      period and cancer. Considering its favorable side effect profile, GBP represents
      a beneficial pain adjunctive therapy, beyond neuropathic symptoms.

PMID- 24281282
TI  - Musculoskeletal pain in obese compared with healthy-weight children.
AB  - OBJECTIVES: To investigate whether obesity is associated with musculoskeletal
      pain in children. MATERIALS AND METHODS: Obese (n=107) and healthy-weight (n=132)
      10- to 13-year-old children (132 males, 107 females) participated in an
      observational case-control study. Children self-reported pain location (excluding
      abdominal pain), pain intensity (current and prior week), and pain prevalence
      (overall and lower limb) using the Pediatric Pain Questionnaire. Body composition
      was assessed (dual-energy x-ray absorptiometry) and children wore an
      accelerometer for 8 days. RESULTS: After adjustment for accelerometry (weekly
      average counts per hour) and socioeconomic status, obese children had more
      intense pain (worst pain, P=0.006), pain in more locations (P<=0.005), and a
      higher prevalence of lower limb pain (60% vs. 52% respectively, P=0.012) than
      healthy-weight children. Significant relationships were observed between body
      mass index and total pain locations (P<=0.004, unadjusted and adjusted) and worst
      pain intensity (P<=0.009, adjusted for socioeconomic status/accelerometry). There
      were no significant relationships between percent body fat and pain variables
      (unadjusted/adjusted analyses, P=0.262 to 1.0). DISCUSSION: Obesity in children
      was associated with increased overall and lower limb musculoskeletal pain, for
      which body mass index was a stronger predictor than adiposity. Clinicians
      treating obese children should screen for pain and prescribe exercise programs
      that take their symptoms into account.

PMID- 24281284
TI  - Is lack of habituation of evoked potential a biological marker of migraine?
AB  - OBJECTIVE: The aim of this study was to evaluate sensitization and habituation of
      median somatosensory-evoked potential (MSEP) and correlate with migraine
      characteristics and allodynia. PATIENTS AND METHODS: A total of 100 migraineurs
      were included; their demographic features, migraine characteristics, and the
      presence of allodynia were noted. The patients were grouped into episodic
      migraine (EM), chronic migraine (CM), and medication overuse headache (MOH).
      Three consecutive MSEPs averaging 100 epochs each were recorded. The N19
      amplitude of block 1 was considered for sensitization, and amplitudes of block 2
      and 3 compared with block 1 were considered for habituation and augmentation.
      MSEP was also evaluated in 29 controls. RESULTS: Seventy-one percent of
      migraineurs had a lack of habituation as opposed to 27.6% of controls (P<0.001).
      The lack of habituation was observed in all subtypes of migraine, and patients
      with EM (76.1%) had greater lack of habituation compared with patients with MOH
      (61.3%; P=0.03). Augmentation was present in 61% migraineurs and was more
      frequent in CM (73.9%) compared with EM (63%) and MOH (48%). Sensitization was
      not significantly different in migraineurs compared with controls (8.23+/-4.07
      vs.7.99+/-2.84 MUV; P=0.72), but patients with allodynia had greater
      sensitization compared with those without allodynia (8.57+/-4.32 vs. 6.89+/-2.55
      MUV; P=0.03). The sensitization was also related to age and duration of migraine.
      CONCLUSIONS: The migraineurs have impaired cortical inhibition to somatosensory
      stimuli, and sensitization may be a feature of chronicity.

PMID- 24281283
TI  - Cathodal and anodal left prefrontal tDCS and the perception of control over pain.
AB  - OBJECTIVES: The prefrontal cortex may be a promising target for the use of
      transcranial direct current stimulation (tDCS) in the management of pain
      symptoms. The present study explored the effects of anodal and cathodal tDCS over
      the left dorsolateral prefrontal cortex on the effects of perceived pain
      controllability. MATERIALS AND METHODS: Forty-one participants received
      continuous anodal or cathodal tDCS and underwent a laboratory pain task designed
      to manipulate the perception of pain control. Participants were told that they
      would be completing a reaction-time task (press keyboard button of corresponding
      arrow shown on computer screen with either green or red background). A thermal
      pain stimulus was delivered following each trial by a thermode placed on the
      participant's left forearm. Although pain stimuli were pseudorandomally ordered
      and matched for total duration between control (green) and noncontrol (red)
      trials, participants were told that if they responded correctly and more quickly
      on green trials than their average reaction times, the thermal pain stimulus
      duration would be decreased (ie, perceived control). Participants were told they
      had no control of pain stimulus duration over trials presented with the red
      background. RESULTS: There was a significant main effect for tDCS condition
      (anode vs. cathode) on pain unpleasantness ratings (P<0.04). Specifically,
      individuals receiving cathodal tDCS reported higher pain unpleasantness ratings
      (least squares mean=69.40, SE=3.72), whereas those receiving anodal tDCS reported
      lower pain unpleasantness ratings (least squares mean=58.05, SE=3.81).
      Exploratory analysis revealed a simple main effect for tDCS group at the level of
      perceived controllability (P<0.02). In addition, participants receiving cathodal
      tDCS subjectively reported feeling less control of the painful stimuli than those
      receiving anodal tDCS. DISCUSSION: Left dorsolateral prefrontal cortex tDCS may
      play a role in modulating the neurocircuitry involved with the perception of
      control over pain.

PMID- 24281285
TI  - Short-term effects of a manual therapy protocol on pain, physical function,
      quality of sleep, depressive symptoms, and pressure sensitivity in women and men
      with fibromyalgia syndrome: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the therapeutic effects of a manual therapy protocol
      for improving pain, function, pressure pain thresholds (PPT), quality of sleep,
      and depressive symptoms in women and men with fibromyalgia syndrome (FMS).
      MATERIALS AND METHODS: Eighty-nine patients were randomly assigned to
      experimental or control group. The experimental group (24 female, 21 male)
      received 5 sessions of manual therapy and the control group (24 female, 21 male)
      did not receive any intervention. PPT, pain, impact of FMS symptoms, quality of
      sleep, and depressive symptoms were assessed in both groups at baseline and after
      48 hours of the last intervention in the experimental group. RESULTS: The
      analysis of covariance found significant Group*Time*Sex interactions for McGill
      PPI and Center for Epidemiologic Studies Depressive Symptoms Scale (P<0.01) was
      also found: men exhibited a larger effect size for depressive symptoms than
      women, whereas women exhibited a greater effect size than men in the McGill PPI.
      A significant Group*Time*Sex interaction for PPT over suboccipital, upper
      trapezius, supraspinatus, second rib, gluteal region, and tibialis anterior
      muscle was also found: men included in the experimental group experienced
      significant greater improvements in PPT as compared with women with FMS in the
      experimental group. CONCLUSIONS: Manual therapy protocol was effective for
      improving pain intensity, widespread pressure pain sensitivity, impact of FMS
      symptoms, sleep quality, and depressive symptoms. In addition, sex differences
      were observed in response to treatment: women and men get similar improvements in
      quality of sleep and tender point count, whereas women showed a greater reduction
      in pain and impact of FMS symptoms than men, but men reported higher decreases in
      depressive symptoms and pressure hypersensitivity than women.

PMID- 24281286
TI  - A longitudinal investigation of pain-related social support preferences in a
      chronic pain treatment sample.
AB  - OBJECTIVES: Chronic pain patients' pain-related social support preferences have
      received little clinical or research attention. However, recent research
      utilizing the Pain Response Preference Questionnaire (PRPQ) has indicated that
      such preferences are related to pain-related disability. This study investigated
      whether pain-related social support preferences: (1) were related to disability
      levels, (2) predicted changes in pain and disability following a group-based
      treatment program, and (3) changed from pretreatment to posttreatment. METHODS:
      At pretreatment and posttreatment, chronic pain patients (N=45) participating in
      a self-management psychoeducation program completed the PRPQ and measures of pain
      severity and disability. RESULTS: A multiple regression analysis indicated that
      at pretreatment the Solicitude scale of the PRPQ was positively associated with
      disability, and that this association was moderated by the other 2 PRPQ scales
      (Activity Direction and Suppression). The PRPQ scales did not predict changes in
      pain or disability and there were no significant changes in the PRPQ scale
      scores. However, participants did not respond to the Solicitude scale in a
      consistent manner from pretreatment to posttreatment (51.1% decreased, 35.5%
      increased, and 13.3% remained the same). These changes were unrelated to changes
      in pain or disability. DISCUSSION: Additional research aimed at identifying the
      processes underlying the association between pain-related support preferences and
      disability is warranted. Given the potentially important role that a desire for
      solicitous support may play in shaping the social context of pain, understanding
      the unexpected changes in Solicitude scale scores found in the present study may
      be particularly important for improving self-management treatments for chronic
      pain.

PMID- 24281287
TI  - What do patients do with unused opioid medications?
AB  - OBJECTIVES: The volume of opioid medications being prescribed in the United
      States is increasing rapidly. Problems associated with the misuse of opioid
      medications are also increasing, in part because of medication diversion from
      legitimate prescriptions. However, little is known about what patients do with
      any unused opioid medications. This paper uses a qualitative analysis of
      patients' self-report of medication storage and retention habits to begin to
      address this gap. METHODS: We analyzed responses to the Prescription Drug Use
      Questionnaire in conjunction with other data on prescription opioid use in a
      sample of 191 Veteran patients (83% of whom had a preexisting factor associated
      with higher rates of opioid misuse) who received one or more opioid prescriptions
      in the previous 12 months. RESULTS: Only 6.3% of participants disposed of extra
      medications and 24.1% reported having no extra opioids. A total of 65.4% of
      participants reported retaining some or all opioids even if they ceased taking
      the medication, and some participants accumulated large amounts of medication. A
      total of 34.0% of participants described engaging in sharing or diversion of
      opioids at least once, most often receiving them from a family member or a
      friend. DISCUSSION: A majority of patients retain unused opioids, and medication
      sharing is common. Interventions to improve monitoring of patient experience with
      opioid medication, educate patients about the dangers of opioid use by
      nonprescribed others, and increase information about medication disposal options
      could decrease the supply of opioid medications available for misuse.

PMID- 24281288
TI  - Theoretical repeatability coefficient of a 100 mm visual analog scale in
      children.
AB  - OBJECTIVE: The aim of this study was to determine the theoretical repeatability
      coefficient of a 100 mm visual analog scale (VAS) in children in different
      circumstances. METHODS: A prospective cohort study was conducted using a
      convenience sample of patients aged 8 to 17 years presenting to a pediatric
      emergency department. Patients were asked how they liked a variety of foods
      (surrogate for stable pain stimulus) on a 100 mm VAS with 4 different sets of
      questions repeated 3 times: set 1--questions at 3-minute intervals with no
      specific instructions other than how to complete the VAS; set 2--same format as
      set 1 except for the duration of the interval (1 min); set 3--same as set 1
      except patients were asked to remember their answers; set 4--same as set 1 except
      patients were shown their previous answers. For each, the repeatability
      coefficient of the VAS was determined. RESULTS: A total of 100 patients aged
      12.1+/-2.4 years were enrolled. The repeatability coefficient for the questions
      asked at the 3-minute interval was 12 mm, whereas it was 8 mm when asked at the 1
      minute interval. When asked to remember their previous answers or to reproduce
      them, the repeatability coefficients for the questions were 7 and 6 mm,
      respectively. DISCUSSION: The conditions of the assessments influence the
      repeatability coefficient of the VAS. Depending on different circumstances, the
      repeatability coefficient in children aged 8 to 17 years varies from 6 to 12 mm
      on a 100 mm VAS.

PMID- 24281289
TI  - Breakthrough pain in patients with abdominal cancer pain.
AB  - OBJECTIVE: Characterization of breakthrough cancer pain (BTcP) in patients with
      abdominal cancer is lacking. The aim of this study was to assess the
      characteristics of BTcP in patients with abdominal cancer pain. PATIENTS AND
      METHODS: In an observational cohort study, from a consecutive sample of patients
      admitted to a pain relief and supportive care unit for a period of 13 months,
      patients with abdominal disease due to cancer, including primary cancer or
      metastases, were assessed for the presence of chronic abdominal pain; its
      mechanism, intensity of background pain, and pain flares, which were
      distinguishable from the baseline pain, were recorded. Patients presenting with
      pain flares were assessed regarding the causes and the possible factors
      associated with it. Patients were reassessed when background pain control was
      considered optimal. RESULTS: From a sample of 522 patients admitted to an acute
      pain relief and palliative care unit in a period of 13 months, 100 patients with
      abdominal disease were available. The mean age was 65.3 years (SD+/-11.4); of the
      100 patients, 45 (45%) were males. The mean Karnofsky status was 47.7 (SD+/
      11.1). At admission (T0), 67 patients (67%) had background pain with mean pain
      intensity of 4.9 (SD+/-1.6). Sixty-one patients of those with background pain
      (91%) had superimposed and well-distinguished pain flares. After analgesic
      optimization (T1), the mean background pain intensity was 1.7 (SD+/-1.2), and
      55.2% of patients had BTcP episodes. The difference with T0 was significant
      (P<0.0005). CONCLUSIONS: This preliminary study provides new insights on the
      characteristics of BTcP in a subclass of patients with abdominal disease. It has
      been estimated that about 55% of patients with well-controlled background pain
      will develop BTcP episodes. This percentage was higher (about 90%) in patients
      who presented with uncontrolled background pain, underlying the need to better
      characterize patients with BTcP, only after a careful optimization of basal pain,
      as considered by the definition of BTcP.

PMID- 24281290
TI  - Perioperative epidural or intravenous ketamine does not improve the effectiveness
      of thoracic epidural analgesia for acute and chronic pain after thoracotomy.
AB  - OBJECTIVES: Persistent postsurgical pain (PPP) after thoracotomy effect 50% to
      80%. Nerve damage and central sensitization involving NDMDAr activation may play
      an important role. This study evaluates the efficacy of adding intravenous (IV)
      or epidural ketamine to thoracic epidural analgesia (TEA) after thoracotomy.
      MATERIALS AND METHODS: Double-blind randomized study on patients undergoing
      thoracotomy allocated to one of the following: group Kiv (IV racemic ketamine 0.5
      mg/kg preincisional +0.25 mg/kg/h for 48 h), group Kep (epidural racemic ketamine
      0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), or group S (saline).
      Postoperative analgesia was ensured by TEA with ropivacaine and fentanyl. Pain
      visual analog scales (VAS), Neuropathic Pain Symptom Inventory, Catastrophizing
      Scale, and Quantitative Sensory Testing, measuring both the peri-incisional and
      distant hyperalgesia area, were conducted preoperatively and postoperatively
      until 6 months. Plasma ketamine levels and stability of the analgesic solutions
      were analyzed. RESULTS: A total of 104 patients were included. PPP incidence was
      20% at 6 months. Pain scores on coughing were significantly lower in Kiv and Kep
      than in S at 24 and 72 hours, but there were no differences afterwards. There
      were no significant differences in pain at rest, Neuropathic Pain Symptom
      Inventory, and Catastrophizing Scale, or in the area of mechanical allodynia at
      any time. Adverse effects were mild. Plasma ketamine levels did not differ
      significantly between groups. Analgesic solutions were stable. CONCLUSIONS:
      Adding epidural or IV racemic ketamine to TEA after thoracotomy did not lead to
      any reduction in PPP or allodynia. Epidural administration produced similar
      plasma ketamine levels to the IV route.

PMID- 24281292
TI  - The impact of pain on anxiety and depression is mediated by objective and
      subjective sleep characteristics in fibromyalgia patients.
AB  - OBJECTIVES: Pain is the cardinal feature in fibromyalgia syndrome (FM) and
      increases the risk of anxiety and depression. Patients with FM frequently report
      sleep disturbances as well. Sleep may mediate the association between pain and
      emotional symptoms, an idea which has been scarcely studied. The objective of
      this study was to uncover the role of subjective and objective sleep
      characteristics as mediators of the relationship between pain and anxiety and
      depression in FM. MATERIALS AND METHODS: Fifty-five female with FM (mean age,
      47.62 +/- 7.64 y) were assessed to obtain self-reported measures of pain, sleep
      quality, anxiety and depression levels, and self-efficacy to cope with pain. An
      ambulatory polysomnographic recording was performed to assess sleep architecture.
      RESULTS: Subjective poor sleep quality was found in all participtants. Pain
      correlated with subjective and objective sleep parameters, self-efficacy,
      anxiety, and, marginally, with depression. The mediated regression analysis
      suggested that the best models to explain the impact of pain on anxiety and
      depression included, as mediators, subjective sleep quality, objective sleep
      efficiency, and self-efficacy (these models explained 34% of the variance), with
      objective sleep efficiency being the mediator with the highest influence
      (P<0.05). DISCUSSION: These findings show a high prevalence of sleep problems in
      individuals with FM and suggest that they play a role in the relationship between
      pain and anxiety and depression. In fact, the impact of chronic pain on the later
      emotional variables was mediated not only by self-efficacy but also by subjective
      sleep quality and, especially, by objective sleep efficiency.

PMID- 24281293
TI  - Urine drug testing in long-term opioid therapy: ethical considerations.
AB  - As long-term opioid analgesic therapy has gained increasing clinical and societal
      acceptance over the past 2 decades, morbidity and mortality related to the misuse
      of these drugs have increased in lockstep. Hence, monitoring for opioid-related
      problems, largely through urine drug testing, has become a central component of
      risk mitigation in long-term opioid therapy. Despite the increasing use of urine
      drug testing, little has been written about the ethical aspects of its
      application. In this paper, we analyze multiple aspects of drug testing-rationale
      for testing, specimen collection, ordering and interpretation, and response to
      inappropriate test results-through the principlist lens, using the ethical
      principles of beneficence, nonmaleficence, justice, and autonomy. 

PMID- 24281291
TI  - Change in suicidal ideation after interdisciplinary treatment of chronic pain.
AB  - OBJECTIVES: To examine suicidal ideation (SI) in individuals with chronic pain,
      especially change in suicidal thinking after interdisciplinary treatment.
      MATERIALS AND METHODS: Consecutive patients (n=250) admitted to a 4-week, group
      based chronic pain management program completed measures of pain intensity,
      functional limitations, depressive symptoms, overall distress, pain
      catastrophizing, self-perceived burden, and SI at pretreatment and posttreatment.
      RESULTS: Before treatment, 30 (12.0%) participants were classified as having a
      high level of SI, 56 (22.4%) had a low level of SI, and 164 (65.6%) reported
      none. After treatment, there was a significant reduction in SI and improvements
      in all other outcomes, but there were still some individuals with high (n=22,
      8.8%) or low (n=28, 11.2%) levels at discharge. Patients with high SI at baseline
      differed from those with no suicidal thinking on pretreatment and posttreatment
      measures of depression, distress, catastrophizing, and self-perceived burden, but
      not on pain intensity or functional limitations. Patients high in SI endorsed
      greater pain catastrophizing and self-perceived burden than those low in suicidal
      thinking. Sustained SI after treatment was associated with higher baseline levels
      of suicidal thinking and self-perceived burden to others, as well as a more
      limited overall response to treatment. DISCUSSION: SI was common in individuals
      with chronic pain, although mostly at a low level. Interdisciplinary treatment
      may result in reduced suicidal thinking; however, some patients continue to
      express thoughts of self-harm. Future studies could examine processes of change
      and interventions for treatment-resistant suicidal concerns.

PMID- 24281294
TI  - Evidence-based development and initial validation of the pain assessment
      checklist for seniors with limited ability to communicate-II (PACSLAC-II).
AB  - OBJECTIVES: Our goal was to develop and validate, based on theoretical and
      empirical knowledge, the Pain Assessment Checklist for Seniors with Limited
      Ability to Communicate (PACSLAC-II), a shorter tool that would improve on the
      PACSLAC, while addressing limitations of the original version. METHODS: The
      PACSLAC was revised based on the relevant clinical and theoretical literature.
      Psychometric properties and clinical utility of the resulting 31-item PACSLAC-II
      were examined. Specifically, the PACSLAC-II was used to assess pain based on
      video footage of long-term care (LTC) residents with dementia undergoing painful
      procedures as part of routine care. Its ability to discriminate pain from non
      pain-related states was compared with that of preexisting pain assessment tools
      using archival data. A second phase involved the use of the PACSLAC and PACSLAC
      II by LTC staff to solicit feedback from health care providers. Mixed-methods
      analysis of this feedback was conducted. RESULTS: The PACSLAC-II demonstrated
      satisfactory reliability, excellent validity, and ability to differentiate
      between pain and nonpain states. The PACSLAC-II also accounted for unique
      variance in differentiating between pain and nonpain states, even after
      controlling for the preexisting tools combined, including the PACSLAC. The
      PACSLAC-II was also preferred by many LTC nurses and care aides, because of its
      length and condensed nature, which was thought to facilitate documentation and
      greater efficiency in pain management. DISCUSSION: Findings indicate that the
      empirical and theoretically driven revisions to the PACSLAC led to improved
      ability to differentiate between pain and nonpain states, while retaining its
      clinical utility.

PMID- 24281295
TI  - Single-day pain assessments as clinical outcomes: not so fast.
AB  - INTRODUCTION: Pain diaries are important tools for clinical trials and optimal
      assay sensitivity of outcomes derived from these diaries is a worthwhile goal.
      Jensen and colleagues recently reported results suggesting that single-day diary
      based outcomes could possibly be as psychometrically sound as outcomes based on
      taking the average of many diaries. MATERIALS AND METHODS: In this paper, we
      attempted to replicate those results with several diary data sets. RESULTS AND
      DISCUSSION: We come to a different conclusion than that advanced by Jensen and
      colleagues and conclude that their results were unusual in that very high test
      retest reliability among days was found. With our 4 diary data sets we find that
      aggregating multiple diaries yields more reliable outcomes and improved
      sensitivity. We suggest that using single-day diaries will often lead to
      underpowered studies and that pretesting is advised before adopting single-day
      diaries. We also suggest that other researchers replicate these findings within
      their diary-based clinical trials.

PMID- 24281297
TI  - Enhanced reversibility and durability of a solid oxide Fe-air redox battery by
      carbothermic reaction derived energy storage materials.
AB  - The recently developed solid oxide metal-air redox battery is a new technology
      capable of high-rate chemistry. Here we report that the performance,
      reversibility and stability of a solid oxide iron-air redox battery can be
      significantly improved by nanostructuring energy storage materials from a
      carbothermic reaction. 

PMID- 24281298
TI  - Organic causes of erectile dysfunction in men under 40.
AB  - There are a significant number of men under 40 who experience erectile
      dysfunction (ED). In the past, the vast majority of cases were thought to be
      psychogenic in nature. Studies have identified organic etiologies in 15-72% of
      men with ED under 40. Organic etiologies include vascular, neurogenic, Peyronie's
      disease (PD), medication side effects and endocrinologic sources. Vascular causes
      are commonly due to focal arterial occlusive disease. Young men with multiple
      sclerosis, epilepsy and trauma in close proximity to the spinal cord are at
      increased risk of ED. It is estimated that 8% of men with PD are under 40, with
      21% of these individuals experiencing ED. Medications causing ED include
      antidepressants, NSAIDs and finasteride (Propecia), antiepileptics and
      neuroleptics. Hormonal sources are uncommon in the young population, however
      possible etiologies include Klinefelter's syndrome, congenital hypogonadotropic
      hypogonadism, and acquired hypogonadotropic hypogonadism. The workup of young men
      with ED should include a thorough history and physical examination. The
      significant prevalence of vascular etiologies of ED in young men should prompt
      consideration of nocturnal penile tumescence testing and penile Doppler
      ultrasound. Treatment options that may improve ED include exercise and oral PDE-5
      inhibitors.

PMID- 24281296
TI  - Psychological well-being revisited: advances in the science and practice of
      eudaimonia.
AB  - This article reviews research and interventions that have grown up around a model
      of psychological well-being generated more than two decades ago to address
      neglected aspects of positive functioning such as purposeful engagement in life,
      realization of personal talents and capacities, and enlightened self-knowledge.
      The conceptual origins of this formulation are revisited and scientific products
      emerging from 6 thematic areas are examined: (1) how well-being changes across
      adult development and later life; (2) what are the personality correlates of well
      being; (3) how well-being is linked with experiences in family life; (4) how well
      being relates to work and other community activities; (5) what are the
      connections between well-being and health, including biological risk factors, and
      (6) via clinical and intervention studies, how psychological well-being can be
      promoted for ever-greater segments of society. Together, these topics illustrate
      flourishing interest across diverse scientific disciplines in understanding
      adults as striving, meaning-making, proactive organisms who are actively
      negotiating the challenges of life. A take-home message is that increasing
      evidence supports the health protective features of psychological well-being in
      reducing risk for disease and promoting length of life. A recurrent and
      increasingly important theme is resilience - the capacity to maintain or regain
      well-being in the face of adversity. Implications for future research and
      practice are considered.

PMID- 24281299
TI  - Photoheterotrophic growth of Physcomitrella patens.
AB  - Physcomitrella patens is a model bryophyte representing an early land plant in
      the green plant lineage. This organism possesses many advantages as a model
      organism. Its genome has been sequenced, its predominant life cycle stage is the
      haploid gametophyte, it is readily transformable and it can integrate transformed
      DNA into its genome by homologous recombination. One limitation for the use of P.
      patens in photosynthesis research is its reported inability to grow
      photoheterotrophically, in the presence of sucrose and the Photosystem II
      inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, which prevents linear
      photosynthetic electron transport. In this communication we describe the facile
      isolation of a P. patens strain which can grow photoheterotrophically.
      Additionally, we have examined a number of photosynthetic parameters for this
      strain grown under photoautotrophic, mixotrophic (in the presence of sucrose) and
      photoheterotrophic conditions, as well as the 3-(3,4-dichlorophenyl)-1,1
      dimethylurea-inhibited state. The ability to grow P. patens
      photoheterotrophically should significantly facilitate its use in photosynthetic
      studies. 

PMID- 24281300
TI  - Thank you my friends.

PMID- 24281301
TI  - Response to Evens et al., racial disparities in Hodgkin's lymphoma: a
      comprehensive population-based analysis, Annals of Oncology 23: 2128-2137, 2012.

PMID- 24281302
TI  - The structural properties of DNA regulate gene expression.
AB  - Regulatory sequences such as promoters not only contain cis-regulatory elements
      as switches of transcription, but also exhibit particular topological features.
      In this paper, we introduce a systematic genome scale approach to characterize
      the roles of structural conformation and stability profile of promoter sequence
      in gene expression. The average free energy of promoter dinucleotides stacking
      nearest neighbors are subjected to scrutiny by statistical hidden Markov models
      to reveal the function of constrains and properties of promoter structure in
      transcription. When applied for a 1000 bp 5' upstream sequence of genes, the
      proposed model via assessing free energy profile identified co-expressed genes of
      Arabidopsis thaliana in response to the auxin hormone. The applied perspective
      dynamic network which mediates transcription regulation provides a great
      hindrance to conceive how DNA conformation interacts with cis-regulatory
      elements, chromatin structure and many other factors. This study indeed drew the
      complexity of the promoter's regulatory behavior from sequence over the former
      studies and evokes a new hypothesis to be validated experimentally. 

PMID- 24281303
TI  - General nature of liquid-liquid transition in aqueous organic solutions.
AB  - The presence or absence of a liquid-liquid transition in water is one of the hot
      topics in liquid science, and while a liquid-liquid transition in water/glycerol
      mixtures is known, its generality in aqueous solutions has remained elusive. Here
      we reveal that 14 aqueous solutions of sugar and polyol molecules, which have an
      ability to form hydrogen bonding with water molecules, exhibit liquid-liquid
      transitions. We find evidence that both melting of ice and liquid-liquid
      transitions in all these aqueous solutions are controlled solely by water
      activity, which is related to the difference in the chemical potential between an
      aqueous solution and pure water at the same temperature and pressure. Our theory
      shows that water activity is determined by the degree of local tetrahedral
      ordering, indicating that both phenomena are driven by structural ordering
      towards ice-like local structures. This has a significant implication on our
      understanding of the low-temperature behaviour of water. 

PMID- 24281304
TI  - Red-light initiated atmospheric reactions of vibrationally excited molecules.
AB  - We present a brief review of long wavelength, red-light initiated chemistry from
      excited vibrational levels of the ground electronic state of atmospheric trace
      species. When sunlight driven electronic state reactions are not effective,
      photochemical processes occurring by vibrational overtone excitation have been
      found to be important in reactions of oxidized atmospheric compounds (acids,
      alcohols and peroxides) prevalent in the Earth's atmosphere. This review focuses
      on the fundamental energetic, mechanistic and dynamical aspects of unimolecular
      reactions of vibrationally excited atmospheric species. We will discuss the
      relevance of these red light initiated reactions to address the discrepancies
      between atmospheric measurements and results of standard atmospheric models. 

PMID- 24281305
TI  - Entropy and order in urban street networks.
AB  - Many complex networks erase parts of their geometry as they develop, so that
      their evolution is difficult to quantify and trace. Here we introduce entropy
      measures for quantifying the complexity of street orientations and length
      variations within planar networks and apply them to the street networks of 41
      British cities, whose geometric evolution over centuries can be explored. The
      results show that the street networks of the old central parts of the cities have
      lower orientation/length entropies - the streets are more tightly ordered and
      form denser networks - than the outer and more recent parts. Entropy and street
      length increase, because of spreading, with distance from the network centre.
      Tracing the 400-year evolution of one network indicates growth through
      densification (streets are added within the existing network) and expansion
      (streets are added at the margin of the network) and a gradual increase in
      entropy over time. 

PMID- 24281306
TI  - Cyclooxygenase (COX) Inhibitors and the Newborn Kidney.
AB  - This review summarizes our current understanding of the role of cyclo-oxygenase
      inhibitors (COXI) in influencing the structural development as well as the
      function of the developing kidney. COXI administered either during pregnancy or
      after birth can influence kidney development including nephronogenesis, and can
      decrease renal perfusion and ultrafiltration potentially leading to acute kidney
      injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a
      more important role in during fetal development and influences kidney function
      early in life is not known, though evidence points to a predominant role for COX
      2. Clinical implications of the use of COXI in pregnancy and in the newborn
      infant are also evaluated herein, with specific reference to the potential
      effects of COXI on nephronogenesis as well as newborn kidney function. 

PMID- 24281309
TI  - Evaluation of the antipruritic effects of topical pimecrolimus in non-atopic
      prurigo nodularis: results of a randomized, hydrocortisone-controlled, double
      blind phase II trial.
AB  - BACKGROUND: In the treatment of atopic dermatitis, pimecrolimus has high
      antipruritic effects. OBJECTIVE: To investigate the efficacy of 1% pimecrolimus
      cream in comparison to 1% hydrocortisone cream in non-atopic prurigo nodularis
      (PN). METHODS: A randomized, controlled, double-blind study with intraindividual
      randomization was done in 30 patients (17 females, 13 males; mean age 58.5 years)
      with PN. RESULTS: Pruritus intensity decreased significantly (p < 0.001) on both
      treated sides as early as after 10 days of treatment; scratch lesions improved (p
      < 0.001). Quality of life as assessed by the Dermatology Life Quality Index
      improved significantly. However, a significant advantage of pimecrolimus over
      hydrocortisone was not found. CONCLUSION: The results suggest that the non
      steroid pimecrolimus is an effective alternative for PN treatment.

PMID- 24281307
TI  - The role of transport mechanisms in mycobacterium tuberculosis drug resistance
      and tolerance.
AB  - In the fight against tuberculosis, cell wall permeation of chemotherapeutic
      agents remains a critical but largely unsolved question. Here we review the major
      mechanisms of small molecule penetration into and efflux from Mycobacterium
      tuberculosis and other mycobacteria, and outline how these mechanisms may
      contribute to the development of phenotypic drug tolerance and induction of drug
      resistance. M. tuberculosis is intrinsically recalcitrant to small molecule
      permeation thanks to its thick lipid-rich cell wall. Passive diffusion appears to
      account for only a fraction of total drug permeation. As in other bacterial
      species, influx of hydrophilic compounds is facilitated by water-filled open
      channels, or porins, spanning the cell wall. However, the diversity and density
      of M. tuberculosis porins appears lower than in enterobacteria. Besides,
      physiological adaptations brought about by unfavorable conditions are thought to
      reduce the efficacy of porins. While intracellular accumulation of selected drug
      classes supports the existence of hypothesized active drug influx transporters,
      efflux pumps contribute to the drug resistant phenotype through their natural
      abundance and diversity, as well as their highly inducible expression. Modulation
      of efflux transporter expression has been observed in phagocytosed, non
      replicating persistent and multi-drug resistant bacilli. Altogether, M.
      tuberculosis has evolved both intrinsic properties and acquired mechanisms to
      increase its level of tolerance towards xenobiotic substances, by preventing or
      minimizing their entry. Understanding these adaptation mechanisms is critical to
      counteract the natural mechanisms of defense against toxic compounds and develop
      new classes of chemotherapeutic agents that positively exploit the influx and
      efflux pathways of mycobacteria. 

PMID- 24281308
TI  - The Biological Role of PI3K Pathway in Lung Cancer.
AB  - Lung cancer is the primary cause of cancer-related mortality worldwide and
      although improvements in treatment have been achieved over the last few years,
      long-term survival rates for lung cancer patients remain poor. Therefore, there
      is an imperative need for molecularly targeted agents that will achieve long-term
      disease control. Numerous downstream molecular pathways, such as
      EGF/RAS/RAF/MEK/ERK and PI3K/AKT/mTOR are identified as having a key role in the
      pathogenesis of various forms of human cancer, including lung cancer.
      PI3K/AKT/mTOR signal pathway is an important intracellular signal transduction
      pathway with a significant role in cell proliferation, growth, survival, vesicle
      trafficking, glucose transport, and cytoskeletal organization. Aberrations in
      many primary and secondary messenger molecules of this pathway, including
      mutations and amplifications, are accounted for tumor cell proliferation,
      inhibition of apoptosis, angiogenesis, metastasis and resistance to chemotherapy
      radiotherapy. In this review article, we investigate thoroughly the biological
      role of PI3K pathway in lung cancer and its contribution in the development of
      future therapeutic strategies. 

PMID- 24281310
TI  - Views of parents in four European countries about the effect of food on the
      mental performance of primary school children.
AB  - BACKGROUND/OBJECTIVES: Several factors affect the mental performance of children.
      The importance that parents attribute to food-related determinants, compared with
      genetic, socio-economic and school environment, was investigated.
      SUBJECTS/METHODS: Parents of school children (aged 4-11) were recruited through
      state primary schools in four European countries. Interviews were conducted in
      which participants were asked to sort 18 cards representing possible determinants
      of four elements of mental performance (attention, learning, mood and behaviour)
      according to perceived strength of effect. Determinants were identified from the
      literature and grouped in six categories: food-related, school environment,
      physical, social, psychological and biological. Effects were scored: 0=none;
      1=moderate; and 2=strong. Views were compared between and within countries.
      RESULTS: Two hundred parents took part (England: 53; Germany: 45; Hungary: 52;
      Spain: 50). Differences existed between countries in the proportions reporting
      university education and being in employment. Taking all countries together,
      parents consider the food category (mean 1.33) to have a lower impact on a
      child's mental performance than physical (activity and sleep, 1.77),
      psychological (mood and behaviour, 1.69) and school environment (1.57). Social
      (1.12) and biological (0.91) determinants were ranked lower than food. Of
      determinants in the food category, parents thought regularity of meals had more
      influence on mental performance (1.58) than what a child eats now (1.36), food at
      school (1.35), nutrition as a baby/infant (1.02). CONCLUSION: Scope exists to
      improve parental awareness of the repercussions of their dietary choices for the
      mental performance of their children.

PMID- 24281311
TI  - Sugar-sweetened beverages consumption in relation to changes in body fatness over
      6 and 12 years among 9-year-old children: the European Youth Heart Study.
AB  - BACKGROUND/OBJECTIVES: In parallel with the obesity epidemic, consumption of
      sugar-sweetened beverages (SSB) has risen over the same period. Our aim was to
      investigate associations between the consumption of SSB in childhood and
      adolescence with subsequent changes in body fatness in early adulthood.
      SUBJECTS/METHODS: A longitudinal study of 9-year-old children (n=283) enrolled in
      the Danish part of the European Youth Heart Study with a 6-year and 12-year
      follow-up. Data were collected at ages 9, 15 and 21 years. Multivariate
      regression analyses with adjustment for potential confounders were used to
      evaluate the effect of SSB consumption at 9 and 15 years and change in SSB
      consumption from 9-15 years on subsequent change in body fatness until 21 years.
      RESULTS: Subjects who consumed more than one serve of SSB daily at age 15 years
      had larger increases in body mass index (BMI) (beta=0.92, P=0.046) and waist
      circumference (WC) (beta=2.69, P=0.04) compared to non-consumers over the
      subsequent 6 years. In addition, subjects who increased their SSB consumption
      from age 9-15 years also had larger increases in BMI (beta=0.91, P=0.09) and WC
      (beta=2.72, P=0.04) from 15-21 years, compared to those who reported no change in
      consumption. No significant association was observed from 9-21 years. CONCLUSION:
      This study provides new evidence that SSB consumption in adolescence and changes
      in SSB consumption from childhood to adolescence are both significant predictors
      of change in body fatness later in early adulthood.

PMID- 24281312
TI  - Can we shorten the lactose tolerance test?
AB  - BACKGROUND: Lactose malabsorption (LM) is a very common problem with high
      prevalence in Southern Europe. The lactose tolerance test (LTT) is a basic probe,
      which is widespread in local hospitals, because it requires non-complex and
      inexpensive infrastructure. The aims of our study are to determine that a
      reduction in the duration of LTT does not affect its diagnostic accuracy to
      detect LM and to calculate the savings that this reduction may represent.
      METHODS: A prospective study of consecutive patients who underwent LTT for
      suspected LM was conducted. We analyzed and compared the clinical results and
      costs (extraction, analytical measurement, time spent by nursing staff,
      technicians and patients) of suppressing LTT points at 30 and 120 min. RESULTS:
      The study included 201 patients. Pathological LTT was found in 119 cases.
      Eliminating the measurement of glucose at 120 min did not alter the LTT
      interpretation in any patient; however, up to 18.4% of patients had a LTT
      misinterpretation when the 30 min point was suppressed. If the LTT 120 min
      measurement would have been suppressed, 41,334 euros could have been saved.
      CONCLUSIONS: Suppressing the 120 min LTT point does not imply any changes in
      clinical results and reduces patient's waiting time; it also benefits the health
      system by saving time, manpower and materials.

PMID- 24281313
TI  - An approach to quantifying abnormalities in energy expenditure and lean mass in
      metabolic disease.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to develop approaches to
      expressing resting energy expenditure (REE) and lean body mass (LM) phenotypes of
      metabolic disorders in terms of Z-scores relative to their predicted healthy
      values. SUBJECTS/METHODS: Body composition and REE were measured in 135 healthy
      participants. Prediction equations for LM and REE were obtained from linear
      regression and the range of normality by the standard deviation of residuals.
      Application is demonstrated in patients from three metabolic disorder groups
      (lipodystrophy, n=7; thyrotoxicosis, n=16; and resistance to thyroid hormone
      (RTH), n=46) in which altered REE and/or LM were characterised by departure from
      the predicted healthy values, expressed as a Z-score. RESULTS: REE (kJ/min) = 
      0.010 * age (years)+0.016 * FM (kg)+0.054 * fat-free mass (kg)+1.736 (R2 = 0.732,
      RSD = 0.36 kJ/min). LM (kg)=5.30 * bone mineral content (kg)+10.66 * height2
      (m)+6.40 (male). LM (kg)=0.20 * fat (kg)+14.08 * height2 (m)-2.93 (female).(male
      R2=0.55, RSD = 3.90 kg; female R2 = 0.59, RSD=3.85 kg).We found average Z-scores
      for REE and LM of 1.77 kJ/min and -0.17 kg in the RTH group, 5.82 kJ/min and 
      1.23 kg in the thyrotoxic group and 2.97 kJ/min and 4.20 kg in the LD group.
      CONCLUSION: This approach enables comparison of data from individuals with
      metabolic disorders with those of healthy individuals, describing their departure
      from the healthy mean by a Z-score.

PMID- 24281316
TI  - Pharmacologic therapy for erectile dysfunction and its interaction with the
      cardiovascular system.
AB  - Phosphodiesterase (PDE) enzymes are widely distributed throughout the body,
      having numerous effects and functions. The PDE type 5 (PDE5) inhibitors are
      widely used to treat erectile dysfunction (ED). Recent, intense preclinical and
      clinical research with PDE5 inhibitors has shed light on new mechanisms and has
      revealed a number of pleiotropic effects on the cardiovascular (CV) system. To
      date, PDE5 inhibition has been shown to be effective for the treatment of
      idiopathic pulmonary arterial hypertension, and both sildenafil and tadalafil are
      approved for this indication. However, current or future PDE5 inhibitors have the
      potential of becoming clinically useful in a variety of CV conditions such as
      heart failure, coronary artery disease, and hypertension. The present review
      discusses recent findings regarding pharmacologic treatment of ED and its
      interaction with the CV system and highlights current and future clinical
      applications beyond ED. 

PMID- 24281317
TI  - Chest X-ray interpretation: not just black and white.

PMID- 24281318
TI  - Age dependency of successful recanalization in anterior circulation stroke: the
      ENDOSTROKE study.
AB  - BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal
      anterior circulation stroke is often disappointing despite high recanalization
      rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in
      patients undergoing EVT. Here we focus on the impact of age and recanalization on
      proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS:
      ENDOSTROKE is an investigator-initiated, industrially independent multicenter
      registry launched in January, 2011, for consecutive patients undergoing EVT for
      large-vessel stroke. This analysis focuses on patients treated in 11 academic and
      nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or
      carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in
      Myocardial Infarction (TIMI) score 2 or 3, and in patients with available
      Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good
      outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3
      months or later. RESULTS: The median age was 68 years (25th and 75th percentiles:
      56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS)
      score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS
      scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached
      TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower
      initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels.
      Outcome was highly dependent on patients' age: 60% of the patients within the
      lowest age quartile (range: 18-56 years) experienced good clinical outcome,
      decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the
      highest age quartile (77-94 years). The proportion of patients with poor clinical
      outcome despite TIMI 2/3 recanalization ('futile recanalization') increased
      dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and
      3rd age quartiles) up to 53% in the highest age quartile. Results were similar in
      patients with available TICI scores, with 'futile recanalization' rates
      increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This
      study emphasizes the dramatic impact of patients' age on outcome in EVT for M1
      MCA or carotid T occlusion, even in the presence of recanalization. Reasons for
      this age-related decrease in clinically successful recanalization rates urgently
      need clarification and may comprise patient-related factors (age-related increase
      in cardioembolic strokes, collateral status, comorbidities) as well as
      periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent
      negative impact of general anesthesia in EVT).

PMID- 24281319
TI  - Pancreatic hepatoid carcinoma: a review of the literature.
AB  - BACKGROUND: Hepatoid carcinomas (HCs) are extrahepatic neoplasms exhibiting
      features of hepatocellular tumors in terms of morphology and
      immunohistochemistry. They have been described in several organs, most notably in
      the stomach and ovary. They can present in pure forms or in association with
      other morphological aspects, such as endocrine tumors or ductal adenocarcinomas.
      The aim of this review is to describe aspects of hepatoid adenocarcinoma of the
      pancreas with regard to epidemiology, diagnosis, and treatment. METHODS: The
      PubMed database was searched for publications addressing hepatoid adenocarcinoma
      of the pancreas. We have searched for articles including the following keywords:
      'pancreatic hepatoid carcinoma', 'ectopic liver cancer' and 'rare pancreas
      neoplasm' published to date. As references, we used case reports and review
      articles. RESULTS: Pancreatic forms of HCs are extremely uncommon: only 22 cases
      have been reported. CONCLUSIONS: The possibility of an HC of the pancreas should
      be considered in the differential diagnosis of an uncommon pathological mass of
      the pancreas. Treatment seems to be related to the association with other
      neoplasms, tumor extension at the time of diagnosis and the possibility to
      perform a radical resection. The common embryologic origin of the pancreas and
      liver, together with peculiar environmental factors, may explain the development
      of pancreatic HCs.

PMID- 24281321
TI  - Positional priming of pop-out is nested in visuospatial context.
AB  - The present study investigated facilitatory and inhibitory positional priming
      using a variant of Maljkovic and Nakayama's (1996) priming of pop-out task. Here,
      the singleton target and the distractors could be presented in different
      visuospatial contexts-but identical screen locations-across trials, permitting
      positional priming based on individual locations to be disentangled from priming
      based on interitem configural relations. The results revealed both significant
      facilitatory priming, i.e., faster reaction times (RTs) to target presented at
      previous target relative to previously empty locations, and inhibitory priming,
      i.e., slower RTs to target at previous distractor relative to previously empty
      locations. However, both effects were contingent on repetitions versus changes of
      stimulus arrangement: While facilitation of target locations was dependent on the
      repetition of the exact item configuration (e.g., T-type followed by T-type
      stimulus arrangement), the inhibitory effect was more "tolerant," being
      influenced by repetitions versus changes of the item's visuospatial category (T
      type followed by Z-type pattern; cf. Garner & Clement, 1963). The results suggest
      that facilitatory and inhibitory priming are distinct phenomena (Finke et al.,
      2009) and that both effects are sensitive to subtle information about the
      arrangement of the display items (Geyer, Zehetleitner, & Muller, 2010). The
      results are discussed with respect to the stage(s) of visual pop-out search that
      are influenced by positional priming. 

PMID- 24281322
TI  - Analysis of plant ribosomes with asymmetric flow field-flow fractionation.
AB  - Ribosome profiling is a technique used to separate ribosomal subunits, 80S
      ribosomes (monosomes), and polyribosomes (polysomes) from other RNA-protein
      complexes. It is traditionally performed in sucrose gradients. In this study, we
      used asymmetric flow field-flow fractionation (AsFlFFF) to characterize ribosome
      profiles of Nicotiana benthamiana plants. With the optimized running conditions,
      we were able to separate free molecules from ribosomal subunits and intact
      ribosomes. We used various chemical and enzymatic treatments to validate the
      positions of subunits, monosomes, and polysomes in the AsFlFFF fractograms. We
      also characterized the protein and RNA content of AsFlFFF fractions by gel
      electrophoresis and western blotting. The reverse transcription polymerase chain
      reaction (RT-PCR) analysis showed that ribosomes remained bound to messenger RNAs
      (mRNAs) during the analysis. Therefore, we conclude that AsFlFFF can be used for
      ribosome profiling to study the mRNAs that are being translated. It can also be
      used to study the protein composition of ribosomes that are active in translation
      at that particular moment. 

PMID- 24281323
TI  - A critical evaluation of the current state-of-the-art in quantitative imaging
      mass spectrometry.
AB  - Mass spectrometry imaging (MSI) has evolved into a valuable tool across many
      fields of chemistry, biology, and medicine. However, arguably its greatest
      disadvantage is the difficulty in acquiring quantitative data regarding the
      surface concentration of the analyte(s) of interest. These difficulties largely
      arise from the high dependence of the ion signal on the localized chemical and
      morphological environment and the difficulties associated with calibrating such
      signals. The development of quantitative MSI approaches would correspond to a
      giant leap forward for the field, particularly for the biomedical and
      pharmaceutical fields, and is thus a highly active area of current research. In
      this review, we outline the current progress being made in the development and
      application of quantitative MSI workflows with a focus on biomedical
      applications. Particular emphasis is placed on the various strategies used for
      both signal calibration and correcting for various ion suppression effects that
      are invariably present in any MSI study. In addition, the difficulties in
      validating quantitative-MSI data on a pixel-by-pixel basis are highlighted. 

PMID- 24281324
TI  - Towards the identification of autologous blood transfusions through capillary
      electrophoresis.
AB  - The use of autologous blood transfusions by endurance athletes has remained one
      of the most difficult doping practices to detect. The implementation of the
      Athlete's Biological Passport by some sporting bodies has proved to be effective;
      however, the analysis relies on the long-term monitoring of numerous biological
      markers, looking for abnormal variations in a number of biological markers to
      indicate doping. This work introduces an approach to identify autologous blood
      transfusions by examining the red blood cells (RBCs) directly. By using high
      speed capillary electrophoretic separations, the relative distribution of the
      sizes of the RBCs in a sample can be established in under 3 min, following the
      preparation of the cells. As RBCs that have been stored for transfusions undergo
      vesiculation, the relative size of the transfused cells differs from the native
      cells. The capillary electrophoretic separation allows for a rapid examination of
      this distribution and the changes that are seen when transfused RBCs are mixed
      with native cells. In this work, the effectiveness of this approach is
      demonstrated in the identification of simulated (in vitro) autologous blood
      transfusions performed with blood samples from three highly trained cyclists; it
      was possible to rapidly identify when as little as 5 % of the RBCs in the sample
      were from a simulated autologous transfusion. 

PMID- 24281325
TI  - Grain shape influence on semiconducting metal oxide based gas sensor performance:
      modeling versus experiment.
AB  - A model for sensing with semiconducting metal oxide (SMOX)-based gas sensors was
      developed which takes the effect of the shape of the grains in the sensing layers
      into account. Its validity is limited to materials in which the grains of the
      SMOX sensing layer are large enough to have an undepleted bulk region (large
      grains). This means that in all experimental conditions, the SMOX properties
      ensure that the influence of surface phenomena is not extended to the whole
      grain. The model takes the surface chemistry and its impact on the electrical
      properties of the sensing material into consideration. In this way, it relates
      the sensor signal--defined as the relative change of the sensor's conductance-
      directly to the concentration of the target gas and also exhibits meaningful
      chemical parameters, such as the type of reactive oxygen species, the reaction
      constants, and the concentration of adsorption sites. The validity of the model
      is confirmed experimentally by applying it to data gathered by measuring homemade
      sensors in relevant conditions.

PMID- 24281320
TI  - The microbiome: stress, health and disease.
AB  - Bacterial colonisation of the gut plays a major role in postnatal development and
      maturation of key systems that have the capacity to influence central nervous
      system (CNS) programming and signaling, including the immune and endocrine
      systems. Individually, these systems have been implicated in the neuropathology
      of many CNS disorders and collectively they form an important bidirectional
      pathway of communication between the microbiota and the brain in health and
      disease. Regulation of the microbiome-brain-gut axis is essential for maintaining
      homeostasis, including that of the CNS. Moreover, there is now expanding evidence
      for the view that commensal organisms within the gut play a role in early
      programming and later responsivity of the stress system. Research has focused on
      how the microbiota communicates with the CNS and thereby influences brain
      function. The routes of this communication are not fully elucidated but include
      neural, humoral, immune and metabolic pathways. This view is underpinned by
      studies in germ-free animals and in animals exposed to pathogenic bacterial
      infections, probiotic agents or antibiotics which indicate a role for the gut
      microbiota in the regulation of mood, cognition, pain and obesity. Thus, the
      concept of a microbiome-brain-gut axis is emerging which suggests that modulation
      of the gut microflora may be a tractable strategy for developing novel
      therapeutics for complex stress-related CNS disorders where there is a huge unmet
      medical need. 

PMID- 24281326
TI  - Development of a new parallelized, optical biosensor platform for label-free
      detection of autoimmunity-related antibodies.
AB  - Autoimmune diseases are characterized by the presence of autoantibodies in serum
      of affected patients. The heterogeneity of autoimmune relevant antigens creates a
      variety of different antibodies, which requires a simultaneous detection mode.
      For this reason, we developed a tool for parallelized, label-free, optical
      detection that accomplishes the characterization of multiple antigen-antibody
      interactions within a single measurement on a timescale of minutes. Using 11
      aminoundecyltrimethoxysilane, we were able to immobilize proteinogenic antigens
      as well as an amino-functionalized cardiolipin on a glass surface. Assay
      conditions were optimized for serum measurements with a single spot antigen chip
      on a single spot 1-lambda detection system. Minimized background signal allows a
      differentiation between patients and healthy controls with a good sensitivity and
      specificity. Applying polarized imaging reflectometric interference spectroscopy,
      we evaluated samples from three APS patients and three control subjects for this
      proof-of-principle and already obtained good results for beta2-glycoprotein I and
      cardiolipin. 

PMID- 24281327
TI  - Dispensation of long-acting beta agonists with or without inhaled
      corticosteroids, and risk of asthma-related hospitalisation: a population-based
      study.
AB  - BACKGROUND: The role of long-acting beta-agonists (LABA) added to inhaled
      corticosteroids (ICS) in the management of asthma is extensively debated. We
      thought to assess the risk of asthma-related hospitalisation in individuals who
      regularly filled prescriptions for ICS+LABA compared to those who regularly
      filled prescriptions for ICS alone or LABA alone, and compared to those who did
      not regularly fill such medications. METHODS: Using administrative health
      databases of the province of British Columbia (BC), Canada, from 1997 to 2012, we
      conducted a nested case-control analysis of a cohort of asthma patients. Cases
      were defined as those who experienced asthma-related hospitalisation after the
      first year of their entry into the cohort. For each case, up to 20 controls were
      matched based on age, sex, date of cohort entry, and several measures of asthma
      severity. We categorised individuals as regularly exposed, irregularly exposed,
      or non-exposed to ICS alone, LABA alone, or ICS+LABA based on dispensation
      records in the past 12 months. The primary outcome measures were the rate ratio
      (RR) of the asthma-related hospitalisation among categories of regular exposure.
      RESULTS: 3319 cases were matched to 43 023 controls. The RR for regular
      dispensation of ICS+LABA was 1.14 (95% CI 0.93 to 1.41) compared with regular
      dispensation of ICS alone and 0.45 (95% CI 0.29 to 0.70) compared with regular
      dispensation of LABA alone. Those who regularly dispensed LABA had to dispense an
      ICS for at least three quarters of a year to reduce their risk to that of those
      who did not dispense LABA. CONCLUSIONS: Regular dispensation of ICS+LABA was not
      associated with an increased risk of asthma-related hospitalisation compared with
      regular dispensation of ICS alone. Adherence to ICS in patients who regularly
      receive ICS+LABA seems to be an important factor in the prevention of adverse
      asthma-related outcomes.

PMID- 24281328
TI  - Encapsulation of [X2(H2O)4]2- (X = F/Cl) clusters by pyridyl terminated tripodal
      amide receptor in aqueous medium: single crystal X-ray structural evidence.
AB  - A new tris-amide receptor L based on 1,3,5-methyl substituted benzene platform
      and pyridyl as an attached unit is synthesized and explored towards anion
      recognition in aqueous environment. The presence of pyridyl terminal in L
      facilitates its aqueous solubility. The binding of halides and oxyanions towards
      L are examined by (1)H-NMR technique in solution and by single crystal X-ray
      crystallography in solid state studies. Crystallization of fluoride and chloride
      with L is carried out in acetone-water (1 : 1, v/v) binary solvent mixture that
      yields crystals for respective host-guest complexes, [L]2.[F2(H2O)4].[TBA]2 (1)
      and [L]2.[Cl2(H2O)4].[TBA]2 (2) suitable for single crystal X-ray diffraction
      studies. On the other hand, complexation of L with fluoride in dioxane-acetone (1
      : 1, v/v) solvent mixture, results the formation of SiF6(2-) encapsulated
      complex, [L]2.[SiF6(H2O)2].[TBA]2 (3). Crystallographic result shows the
      formation of [F2(H2O)4](2-) and [Cl2(H2O)4](2-) zipped 1D-polymeric tweezer-like
      assemblies of L in acetone-water (1 : 1, v/v) binary solvent mixture in complexes
      1 and 2 respectively. Solution state (1)H-NMR studies in D2O-acetone-d6 (1 : 19,
      v/v) support 1 : 4 (host-guest) binding stoichiometry of F(-), Cl(-), Br(-), NO3(
      ), HSO4(-) and H2PO4(-) with L. Binding constants of these investigated anions
      with L by 1 : 1 binding model are calculated which show the following binding
      order: NO3(-) ~ HSO4(-) > F(-) ~ Cl(-) ~ Br(-) > H2PO4(-). Further, solution
      state (19)F-NMR studies are also carried out to establish the F(-) binding with L
      in DMSO-d6.

PMID- 24281329
TI  - Intravascular ultrasound-guided percutaneous coronary interventions: an ongoing
      Odyssey?

PMID- 24281330
TI  - Relationship between intravascular ultrasound guidance and clinical outcomes
      after drug-eluting stents: the assessment of dual antiplatelet therapy with drug
      eluting stents (ADAPT-DES) study.
AB  - BACKGROUND: Prior small to modest-sized studies suggest a benefit of
      intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS
      guidance is associated with improved clinical outcomes after drug-eluting stent
      (DES) implantation in an unrestricted patient population is unknown. METHODS AND
      RESULTS: Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT
      DES) was a prospective, multicenter, nonrandomized "all-comers" study of 8583
      consecutive patients at 11 international centers designed to determine the
      frequency, timing, and correlates of stent thrombosis and adverse clinical events
      after DES. Propensity-adjusted multivariable analysis was performed to examine
      the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in
      3349 patients (39%), and larger-diameter devices, longer stents, and/or higher
      inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared
      with angiography guidance was associated with reduced 1-year rates of
      definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events];
      adjusted hazard radio, 0.40; 95% confidence interval, 0.21-0.73; P=0.003),
      myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95%
      confidence interval, 0.49-0.88; P=0.004), and composite adjudicated major adverse
      cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis)
      (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55
      0.88; P=0.002). The benefits of IVUS were especially evident in patients with
      acute coronary syndromes and complex lesions, although significant reductions in
      major adverse cardiac events were present in all patient subgroups those with
      including stable angina and single-vessel disease. CONCLUSIONS: In ADAPT-DES, the
      largest study of IVUS use to date, IVUS guidance was associated with a reduction
      in stent thrombosis, myocardial infarction, and major adverse cardiac events
      within 1 year after DES implantation. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

PMID- 24281331
TI  - The echo score revisited: Impact of incorporating commissural morphology and
      leaflet displacement to the prediction of outcome for patients undergoing
      percutaneous mitral valvuloplasty.
AB  - BACKGROUND: Current echocardiographic scoring systems for percutaneous mitral
      valvuloplasty (PMV) have limitations. This study examined new, more quantitative
      methods for assessing valvular involvement and the combination of parameters that
      best predicts immediate and long-term outcome after PMV. METHODS AND RESULTS: Two
      cohorts (derivation n=204 and validation n=121) of patients with symptomatic
      mitral stenosis undergoing PMV were studied. Mitral valve morphology was assessed
      by using both the conventional Wilkins qualitative parameters and novel
      quantitative parameters, including the ratio between the commissural areas and
      the maximal excursion of the leaflets from the annulus in diastole. Independent
      predictors of outcome were assigned a points value proportional to their
      regression coefficients: mitral valve area <=1 cm(2) (2), maximum leaflets
      displacement <=12 mm (3), commissural area ratio >=1.25 (3), and subvalvular
      involvement (3). Three risk groups were defined: low (score of 0-3), intermediate
      (score of 5), and high (score of 6-11) with observed suboptimal PMV results of
      16.9%, 56.3%, and 73.8%, respectively. The use of the same scoring system in the
      validation cohort yielded suboptimal PMV results of 11.8%, 72.7%, and 87.5% in
      the low-, intermediate-, and high-risk groups, respectively. The model improved
      risk classification in comparison with the Wilkins score (net reclassification
      improvement 45.2%; P<0.0001). Long-term outcome was predicted by age and
      postprocedural variables, including mitral regurgitation, mean gradient, and
      pulmonary pressure. CONCLUSIONS: A scoring system incorporating new quantitative
      echocardiographic parameters more accurately predicts outcome following PMV than
      existing models. Long-term post-PMV event-free survival was predicted by age,
      degree of mitral regurgitation, and postprocedural hemodynamic data.

PMID- 24281332
TI  - Mitochondrial function in pluripotent stem cells and cellular reprogramming.
AB  - Mitochondria are organelles playing pivotal roles in a range of diverse cellular
      functions, from energy generation to redox homeostasis and apoptosis regulation.
      Their loss of functionality may indeed contribute to the development of aging and
      age-related neurodegenerative disorders. Recently, mitochondria have been shown
      to exhibit peculiar features in pluripotent stem cells (PSCs). Moreover, an
      extensive restructuring of mitochondria has been observed during the process of
      cellular reprogramming, i.e. the conversion of somatic cells into induced
      pluripotent stem cells (iPSCs). These transformation events impact mitochondrial
      number, morphology, activity, cellular metabolism, and mtDNA integrity. PSCs
      retain the capability to self-renew indefinitely and to give rise to virtually
      any cell type of the body and thus hold great promise in medical research.
      Understanding the mitochondrial properties of PSCs, and how to modulate them, may
      thus help to shed light on the features of stemness and possibly increase our
      knowledge on cellular identity and differentiation pathways. Here, we review
      these recent findings and discuss their implications in the context of stem cell
      biology, aging research, and regenerative medicine.

PMID- 24281333
TI  - What we talk about when we talk about randomized controlled trials.

PMID- 24281334
TI  - Sodium taurocholate cotransporting polypeptide mediates dual actions of
      deoxycholic acid in human hepatocellular carcinoma cells: enhanced apoptosis
      versus growth stimulation.
AB  - PURPOSE: The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis
      in hepatocytes. The roles of DC and its transporter are not yet established in
      hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in
      HCC cell growth, with a particular focus on the effect of the expression of bile
      acid (BA)-transporting Na(+)-dependent taurocholic cotransporting polypeptides
      (NTCPs). METHODS: We determined NTCP expression in four human HCC cell lines: Huh
      BAT, Huh-7, SNU-761, and SNU-475. NTCP expression and apoptotic signaling
      cascades were examined by immunoblot analyses. Cell viability was assessed using
      the 3,4-(5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium salt assay. Wound healing and invasion assays were performed to
      evaluate cell migration and invasion abilities. Real-time polymerase chain
      reaction was performed to measure IL-8 expression levels. Nuclear factor kappa B
      (NF-kappaB) activity was evaluated by enzyme-linked immunosorbent assay. RESULTS:
      The HCC cell lines revealed varying NTCP expression levels, and DC treatment had
      dual effects, depending on NTCP expression. DC induced apoptosis in NTCP-positive
      HCC cells, especially under hypoxic conditions. In NTCP-negative HCC cells,
      simultaneous treatment with DC and cyclooxygenase inhibitor markedly decreased
      aggressive cellular behaviors via the inhibition of NF-kappaB/COX-2/IL-8
      pathways. CONCLUSION: Hydrophobic bile acid offers therapeutic potential for
      patients with advanced HCC via different mechanisms depending on NTCP expression
      levels within the tumor.

PMID- 24281335
TI  - Digital PCR quantification of miRNAs in sputum for diagnosis of lung cancer.
AB  - PURPOSE: MicroRNAs (miRNAs) play important roles in the initiation and
      progression of lung cancer. Measuring miRNA expression levels in sputum could
      provide a potential approach for the diagnosis of lung cancer. The emerging
      digital PCR is a straightforward technique for precise, direct, and absolute
      quantification of nucleic acids. The objective of the study was to investigate
      whether digital PCR could be used to quantify miRNAs in sputum for lung cancer
      diagnosis. METHODS: We first determined and compared dynamic ranges of digital
      PCR and conventional quantitative reverse transcriptase PCR (qRT-PCR) for miRNA
      quantification using RNA isolated from sputum of five healthy individuals. We
      then used digital PCR to quantify copy number of two lung cancer-associated
      miRNAs (miR-31 and miR-210) in 35 lung cancer patients and 40 cancer-free
      controls. RESULTS: Copy number of the miRNAs measured by digital PCR displayed a
      linear response to input cDNA amount in a twofold dilution series over seven
      orders of magnitude. miRNA quantification determined by digital PCR assay was in
      good agreement with that obtained from qRT-PCR analysis in sputum. Furthermore,
      combined quantification of miR-31 and miR-210 copy number by using digital PCR in
      sputum of the cases and controls provided 65.71 % sensitivity and 85.00 %
      specificity for lung cancer diagnosis. CONCLUSION: As digital PCR becomes more
      established, it would be a robust tool for quantitative assessment of miRNA copy
      number in sputum for lung cancer diagnosis.

PMID- 24281336
TI  - Cell Penetrating Peptoids (CPPos): Synthesis of a Small Combinatorial Library by
      Using IRORI MiniKans.
AB  - Cell penetrating peptoids (CPPos) are potent mimics of the corresponding cell
      penetrating peptides (CPPs). The synthesis of diverse oligomeric libraries that
      display a variety of backbone scaffolds and side-chain appendages are a very
      promising source of novel CPPos, which can be used to either target different
      cellular organelles or even different tissues and organs. In this study we
      established the submonomer-based solid phase synthesis of a "proof of principle"
      peptoid library in IRORI MiniKans to expand the amount for phenotypic high
      throughput screens of CPPos. The library consisting of tetrameric peptoids
      [oligo(N-alkylglycines)] was established on Rink amide resin in a split and mix
      approach with hydrophilic and hydrophobic peptoid side chains. All CPPos of the
      presented library were labeled with rhodamine B to allow for the monitoring of
      cellular uptake by fluorescent confocal microscopy. Eventually, all the purified
      peptoids were subjected to live cell imaging to screen for CPPos with organelle
      specificity. While highly charged CPPos enter the cells by endocytosis with
      subsequent endosomal release, critical levels of lipophilicity allow other CPPos
      to specifically localize to mitochondria once a certain lipophilicity threshold
      is reached. 

PMID- 24281337
TI  - Synthesis and COX-2 Inhibitory Activity of 4-[(E)-2-(4-Oxo-3-phenyl-3,4
      dihydroquinazolin-2-yl)ethenyl]benzene-1-sulfonamide and Its Analogs.
AB  - Some novel 3-phenyl-2-[(E)-2-phenylethenyl]-3,4-dihydroquinazolin-4-one
      derivatives possessing para-sulfonamides groups on the phenyl ring of the 2
      phenylethenyl moiety have been synthesized and their COX-2 inhibitory activity
      evaluated. The stuctures of the synthesized compounds were confirmed  on the
      basis of  FT-IR, 1H-NMR, 13C-NMR and mass spectral data. The COX-2 inhibition
      screening assay revealed that 4-[(E)-2-{3-(4-methoxyphenyl)-4-oxo-3,4
      dihydroquinazolin-2-yl}ethenyl]benzene-1-sulfonamide had a  maximum COX-2
      inhibition (47.1%), at a concentration of 20 MUM. 

PMID- 24281339
TI  - Integration of ligand-based drug screening with structure-based drug screening by
      combining maximum volume overlapping score with ligand docking.
AB  - Ligand-based and structure-based drug screening methods were integrated for in
      silico drug development by combining the maximum-volume overlap (MVO) method with
      a protein-compound docking program. The MVO method is used to select reliable
      docking poses by calculating volume overlaps between the docking pose in question
      and the known ligand docking pose, if at least a single protein-ligand complex
      structure is known. In the present study, the compounds in a database were docked
      onto a target protein that had a known protein-ligand complex structure. The new
      score is the summation of the docking score and the MVO score, which is the
      measure of the volume overlap between the docking poses of the compound in
      question and the known ligand. The compounds were sorted according to the new
      score. The in silico screening results were improved by comparing the MVO score
      to the original docking score only. The present method was also applied to some
      target proteins with known ligands, and the results demonstrated that it worked
      well. 

PMID- 24281340
TI  - Mechanistic and pharmacological issues of aspirin as an anticancer agent.
AB  - Recent findings have shown that aspirin, taken for several years, reduces the
      long-term risk of some cancers, particularly colorectal cancer. The result that
      aspirin benefit is detectable at daily low-doses (at least 75mg), the same used
      for the prevention of cardiovascular disease, positions the antiplatelet action
      of aspirin at the center of its antitumor efficacy. At low-doses given every 24
      h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase
      (COX)-1 in platelets (in the pre-systemic circulation) while causing a limited
      and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in
      nucleated cells. Aspirin has a short half-life in human circulation
      (approximately 20 min); nucleated cells have the ability to resynthesize the
      acetylated COX-isozymes within a few hours, while platelets do not. COX
      independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and
      NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to
      play a role in its chemo-preventive effects, but their relevance remains to be
      demonstrated in vivo at clinical doses. In conclusion, the results of clinical
      pharmacology and the analysis of randomized and epidemiological studies suggest
      that colorectal cancer and atherothrombosis share a common mechanism of disease,
      i.e. enhanced platelet activation in response to injury at distinct sites. 

PMID- 24281342
TI  - Biosimilars: company strategies to capture value from the biologics market.
AB  - Patents for several biologic blockbusters will expire in the next few years. The
      arrival of biosimilars, the biologic equivalent of chemical generics, will have
      an impact on the current biopharmaceuticals market. Five core capabilities have
      been identified as paramount for those companies aiming to enter the biosimilars
      market: research and development, manufacturing, supporting activities,
      marketing, and lobbying. Understanding the importance of each of these
      capabilities will be key to maximising the value generated from the biologics
      patent cliff. 

PMID- 24281338
TI  - Multiple facets of cAMP signalling and physiological impact: cAMP
      compartmentalization in the lung.
AB  - Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are
      currently used in the treatment of several chronic inflammatory disorders,
      including chronic obstructive pulmonary disease (COPD). Characteristics of COPD
      are airway obstruction, airway inflammation and airway remodelling, processes
      encompassed by increased airway smooth muscle mass, epithelial changes, goblet
      cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway
      smooth muscle cells and (myo)fibroblasts, epithelial cells underpin a variety of
      key responses in the airways such as inflammatory cytokine release, airway
      remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke,
      being next to environmental pollution the main cause of COPD, is believed to
      cause epithelial hyperpermeability by disrupting the barrier function. Here we
      will focus on the most recent progress on compartmentalized signalling by cAMP.
      In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific
      phospho-diesterases (PDEs) maintain compartmentalized cAMP signalling.
      Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to
      involve distinct members of the A-kinase anchoring (AKAP) superfamily and IQ
      motif containing GTPase activating protein (IQGAPs). In this review, we will
      highlight the interaction between cAMP and the epithelial barrier to retain
      proper lung function and to alleviate COPD symptoms and focus on the possible
      molecular mechanisms involved in this process. Future studies should include the
      development of cAMP-sensing multiprotein complex specific disruptors and/or
      stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling
      regulates important cellular processes in the lung and may serve as a therapeutic
      target. 

PMID- 24281341
TI  - The liver as a target organ for gene therapy: state of the art, challenges, and
      future perspectives.
AB  - The liver is a target for gene therapy of inborn errors of metabolism, of
      hemophilia, and of acquired diseases such as liver cancer and hepatitis. The
      ideal gene transfer strategy should deliver the transgene DNA to parenchymal
      liver cells with accuracy and precision in the absence of side effects. Liver
      sinusoids are highly specialized capillaries with a particular endothelial
      lining: the endothelium contains open fenestrae, whereas a basal lamina is
      lacking. Fenestrae provide a direct access of gene transfer vectors to the space
      of Disse, in which numerous microvilli from parenchymal liver cells protrude. The
      small diameter of fenestrae in humans constitutes an anatomical barrier for most
      gene transfer vectors with the exception of adeno-associated viral (AAV) vectors.
      Recent studies have demonstrated the superiority of novel AAV serotypes for
      hepatocyte-directed gene transfer applications based on enhanced transduction,
      reduced prevalence of neutralizing antibodies, and diminished capsid immune
      responses. In a landmark clinical trial, hemophilia B was successfully treated
      with an AAV8 human factor IX expressing vector. Notwithstanding significant
      progress, clinical experience with these technologies remains very limited and
      many unanswered questions warrant further study. Therefore, the field should
      continue to progress as it has over the past decade, cautiously and diligently. 

PMID- 24281344
TI  - What's new in cardiac pacing in children?
AB  - PURPOSE OF REVIEW: To review and prioritize data on pediatric cardiac pacing
      published during the period of the last 18 months. RECENT FINDINGS: New
      approaches to preservation of ventricular function in pediatric pacing are based
      on recent publications confirming major influence of the ventricular pacing site
      on left ventricular (LV) function and synchrony. Current studies on epicardial
      vs. transvenous pacing continue to show survival superiority of endocardial
      leads. Long-term outcome of epicardial pacing may, however, be positively
      influenced by technical refinements. Recent amendments of the guidelines for
      cardiac resynchronization therapy (CRT) in adult idiopathic and ischemic
      cardiomyopathy are likely to influence CRT indications in children. Novel data
      give interesting insights into implantable cardioverter-defibrillator (ICD) lead
      survival as well as the use of ICDs in young patients with hypertrophic
      cardiomyopathy. SUMMARY: Pediatric cardiac pacing and ICD therapy is still a
      developing field likely to improve with technical refinements, proper lead
      placement and more specific therapy indications. The current review will give the
      reader information about recent developments and directions for the future.

PMID- 24281343
TI  - What proportion of chronic obstructive pulmonary disease outpatients is eligible
      for inclusion in randomized clinical trials?
AB  - BACKGROUND AND OBJECTIVE: We aimed to explore to what extent an unselected
      population of chronic obstructive pulmonary disease (COPD) outpatients would be
      eligible for inclusion in randomized clinical trials (RCTs). METHODS:
      Retrospective analysis of the clinical records of outpatient subjects with an
      ascertained diagnosis of COPD. COPD outpatients were assessed against the
      following inclusion criteria: 40 < age < 80 years, current or former smokers,
      forced expiratory volume in the first second (FEV1) <70% predicted, no long-term
      oxygen therapy, no other concomitant lung diseases and absence of major
      extrapulmonary comorbidities. The study consisted of 2 phases; in phase 1, the
      criteria for inclusion in RCTs on COPD were selected, and in phase 2, the above
      criteria were applied to an unselected outpatient COPD population. RESULTS: A
      total of 578 subjects (83% of the whole group) failed at least one of the
      inclusion criteria. Lung diseases other than COPD (occurring in 30% of our
      population, mostly bronchiectasis), long-term oxygen therapy (31%), FEV1 (19%),
      age (14%) and extrapulmonary comorbidities such as cognitive impairment (14%),
      arrhythmias (17%) and congestive heart disease (13%) would have been the most
      frequent causes for exclusion from RCTs. CONCLUSIONS: In real-life settings, more
      than 80% of COPD subjects are currently treated by protocols based on results of
      RCTs for which they would not have been eligible. We encourage a more extensive
      use of pragmatic trials in COPD to better modulate the application of results of
      RCTs to patients encountered in daily practice.

PMID- 24281345
TI  - Mechanisms of persistent atrial fibrillation.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained arrhythmia,
      but its mechanisms are poorly understood. In particular, little is known about
      the factors that contribute to the establishment of persistent or permanent
      atrial fibrillation. This review addresses possible common signaling pathways
      that might promote both structural and electrical remodeling of the atria, thus
      contributing to atrial fibrillation perpetuation. RECENT FINDINGS: Sustained
      atrial fibrillation may trigger an inflammatory response leading to activation of
      myofibroblasts and to the release of cytokines such as transforming growth factor
      beta and platelet-derived growth factor, as well as profibrotic proteins such as
      galectin-3. Activation of signaling cascades involving such proteins is critical
      for the development of fibrosis and may also lead to ion channel dysfunction,
      which, along with myocyte apoptosis and extracellular matrix generation and
      turnover, likely contributes to both electrical and structural remodeling and
      predisposes to atrial fibrillation. SUMMARY: Identifying upstream strategies
      targeting molecular pathways that are common to fibrosis and electrical
      remodeling leading to atrial fibrillation perpetuation is highly desirable. This
      would facilitate finding new target genes with pleiotropic effects on the
      expression of ion channel proteins in myocytes and profibrotic molecules in
      nonmyocyte cells that are important for pathologic remodeling, which could become
      an important goal in persistent atrial fibrillation therapy.

PMID- 24281346
TI  - Aortic dilatation and aortopathies in congenital heart disease.
AB  - PURPOSE OF REVIEW: The objective of this review is to summarize the recent data
      pertaining to aortic dilatation in congenital heart disease (CHD) and to discuss
      the current understanding of the pathophysiology and management of this disease.
      RECENT FINDINGS: Aortic dilatation is a common finding in CHD. However, acute
      aortic complications appear to be relatively rare. Multiple factors predispose
      this population to aortic dilatation, including underlying genetics, cellular
      based mechanisms, and abnormalities in aortic mechanics and valve morphology.
      SUMMARY: Although aortic dilatation is common in CHD, data about adverse long
      term outcomes are limited. Optimal disease-specific management strategies have
      yet to be developed, and further research is needed to guide care in this
      population.

PMID- 24281348
TI  - Screening for undiagnosed atrial fibrillation in the community.
AB  - PURPOSE OF REVIEW: Recent years have seen significant advances in knowledge about
      the prevalence of 'silent' atrial fibrillation and the morbidity associated with
      this condition. Data are emerging on improved strategies for screening, and new
      technologies for detecting atrial fibrillation are becoming available, making a
      review of this field timely. RECENT FINDINGS: Studies suggest that, when
      screening is performed, undiagnosed atrial fibrillation is present in around 1%
      of the screened population, rising to 1.4% for those aged at least 65 years. The
      prevalence of silent atrial fibrillation is even higher in patients with
      additional risk factors (e.g. those aged 75 years, patients with heart failure).
      Prolonged monitoring of patients with hypertension and an implanted cardiac
      device showed subclinical atrial arrhythmias in at least 10% and these patients
      had a 2.5-fold increased risk of stroke or systemic embolism. The feasibility of
      screening for silent atrial fibrillation has been demonstrated in a number of
      populations and many new technologies for atrial fibrillation detection exist,
      which could improve the efficiency and cost-effectiveness of this process.
      SUMMARY: Increased attention is being directed towards screening for silent
      atrial fibrillation and our 'toolbox' for detecting it is expanding. Whether this
      will translate into improved outcomes for patients remains to be proven.

PMID- 24281347
TI  - Will catheter interventions replace surgery for valve abnormalities?
AB  - PURPOSE OF REVIEW: Catheter-based valve technologies have evolved rapidly over
      the last decade. Transcatheter aortic valve replacement (TAVR) has become a
      routine procedure in high-risk adult patients with calcific aortic stenosis. In
      patients with congenital heart disease (CHD), transcatheter pulmonary valve
      replacement represents a transformative technology for right ventricular outflow
      tract dysfunction with the potential to expand to other indications. This review
      aims to summarize the current state-of-the-art for transcatheter valve
      replacement (TVR) in CHD; the expanding indications for TVR; and the
      technological obstacles to optimizing TVR. RECENT FINDINGS: Multiple case series
      have demonstrated that TVR with the Melody transcatheter pulmonary valve in
      properly selected patients is safe, effective, and durable in short-term follow
      up. The Sapien transcatheter heart valve represents an alternative device with
      similar safety and efficacy in limited studies. Innovative use of current valves
      has demonstrated the flexibility of TVR, while highlighting the need for devices
      to address the broad range of postoperative anatomies either with a single device
      or with strategies to prepare the outflow tract for subsequent device deployment.
      SUMMARY: The potential of TVR has not been fully realized, but holds promise in
      treatment of CHD.

PMID- 24281349
TI  - Structure and emission studies of dimorphic crystals of [PtBr2(5,5'
      bis(CF3CH2OCH2)-2,2'-bpy)] (1).
AB  - The yellow (1y) and orange (1o) crystalline polymorphs of [PtBr2(5,5'
      bis(CF3CH2OCH2)-2,2'-bipyridine)] exhibit surprisingly short nearest neighbour
      Pt...Pt separations of 3.526 A and 3.590 A, respectively, at 295 K. Both
      distances are much shorter than those found in structures of the unsubstituted
      [PtBr2(2,2'-bipyridine)] analogue. Consistent with a linear chain structure in 1o
      and dimer formation in 1y, both solids exhibit emission spectra shifted to much
      longer wavelengths than that exhibited by the monomer in a low-temperature glass.
      Furthermore, the emission spectra of 1o and 1y shift to even longer wavelengths
      as the temperature decreases and the Pt...Pt separations contract. Till now
      delocalized emission of this type has been considered to be restricted to
      [PtCl2(diimine)] systems and implausible in PtBr2-containing analogues for steric
      reasons. Ironically, in the system at hand the bulky 5,5'-substituents apparently
      promote delocalization of the emission by forming a network of hydrogen-bonding
      like C-H...F-C interactions that help shape the packing.

PMID- 24281351
TI  - Does the metal protect the ancillary ligands? C-H strengthening and deactivation
      in amines and phosphines upon metal-binding.
AB  - DFT and CCSD(T) calculations show that the weakest C-H bonds of N- and P-donor
      ligands are strengthened and deactivated upon metal-binding. The increase in C-H
      BDE and DeltaG(?) for H abstraction ranges from ca. 1 to 15 kcal mol(-1). 

PMID- 24281350
TI  - Circle of Willis configuration as a determinant of intracranial dolichoectasia.
AB  - BACKGROUND: Circle of Willis (COW) variants might influence arterial caliber in
      the brain. We hypothesized that these variants would be associated with the
      prevalence of intracranial dolichoectasia (DE). METHODS: We examined COW variants
      and DE in a sample of stroke-free participants (n = 436) undergoing magnetic
      resonance angiography (MRA) as part of a population-based study. Large
      intracranial arterial diameters were obtained when available; if not, the artery
      was defined as hypoplastic or absent according to its visibility on MRA.
      Subscores for the anterior and the posterior circulations were created. DE was
      defined as arterial diameters >=2 SD above the population mean for that artery,
      adjusting for intracranial volume. Generalized linear models with a Poisson
      distribution were used to evaluate predictors of both absent and hypoplastic
      vessels, and logistic regression was used to assess the odds ratio (OR) and 95%
      confidence interval (95% CI) of DE depending on COW variants. RESULTS: Only 44%
      of the sample had all 14 arteries present, 32% lacked 1 artery, 18% lacked 2 and
      6% lacked 3 or more. DE of at least 1 artery was not associated with the total
      number of hypoplastic or absent arteries, but DE in a posterior circulation
      artery was weakly associated with the number of absent arteries in the posterior
      circulation (beta coefficient = 0.36, p = 0.06). DE of at least 1 artery was more
      frequent in those with 1 or more absent arteries (OR 1.27, 95% CI 1.03-1.57).
      Posterior circulation DE was more frequent in participants with at least 1 or
      more absent arteries at any location (OR 1.35, 95% CI 1.02-1.78). Participants
      with an incomplete posterior COW were more likely to have DE in the anterior
      circulation (OR 1.52, 95% CI 1.01-2.33). Having an absent left anterior cerebral
      artery (ACA) A1 segment was associated with right ACA DE (OR 34.1, 95% CI 3.16
      368.2); an absent right ACA was associated with left ACA DE (OR 14.1, 95% CI 1.69
      118.28). Absence of 1 (OR 1.9, 95% CI 1.1-3.4) or 2 (OR 3.0, 95% CI 1.4-6.6) of
      the 2 arteries connecting the anterior to the posterior circulation was
      associated with basilar artery DE. CONCLUSION: The COW is a pleomorphic structure
      that allows collateral flow to compensate for an insufficient or absent arterial
      component at the base of the skull. By presumed flow diversion, arteries might
      undergo outward remodeling. Whether this compensatory arterial dilatation is
      beneficial or not remains unknown.

PMID- 24281352
TI  - Galectin-3 coats the membrane of breast cells and makes a signature of tumours.
AB  - Galectin-3, beta-galactoside-binding lectin, coats the membrane of most cancer
      cells and is involved in metastasis and endothelium recognition as well as in
      evading immune surveillance through killing of activated T cells. To flag
      galectin as a biomarker of tumours and metastasis, it is pivotal to understand
      the role of this protein in different tumours and at different stages. Breast
      tumours have an anomalous behaviour of the galectin-3 compared to other tumour
      cells. Herein, FACS sorting and galactoside based assays were used to investigate
      the role of galectin-3 in metastasis and metastatisation of breast cancer cells.
      Breast galectin fingerprint at the FACS displayed a higher amount in healthy
      cells, compared to metastatic cells. The microfluidic assay was able to isolate
      tumour and metastatic cells more than healthy breast cells. Investigation was
      performed on samples from patients with breast tumours at stage I and stage III
      whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The
      readout of the conditioned medium (from culturing of stage I cells) fingerprint
      by FACS evidenced high expression of free galectin. Analysis of the results
      established that the galectin coating the membrane, by galactoside recognition of
      the breast cells, and engaged by the cells to form protein-carbohydrate complexes
      inside the microfluidic assay, resembled the tumour signature of tumours in
      breast cells whilst the galectin free is independent of those mechanisms. 

PMID- 24281354
TI  - Out of phase: relevance of the medial septum for directional hearing and
      phonotaxis in the natural habitat of field crickets.
AB  - A modified tracheal system is the anatomical basis for a pressure difference
      receiver in field crickets, where sound has access to the inner and outer side of
      the tympanum of the ear in the forelegs. A thin septum in the midline of a
      connecting trachea coupling both ears is regarded to be important in producing
      frequency-dependent interaural intensity differences (IIDs) for sound
      localization. However, the fundamental role of the septum in directional hearing
      has recently been challenged by the finding that the localization ability is
      ensured even with a perforated septum, at least under controlled laboratory
      conditions. Here, we investigated the influence of the medial septum on
      phonotaxis of female Gryllus bimaculatus under natural conditions. Surprisingly,
      even with a perforated septum, females reliably tracked a male calling song in
      the field. Although reduced by 5.2 dB, IIDs still averaged at 7.9 dB and provided
      a reliable proximate basis for the observed behavioural performance of operated
      females in the field. In contrast, in the closely related species Gryllus
      campestris the same septum perforation caused a dramatic decline in IIDs over all
      frequencies tested. We discuss this discrepancy with respect to a difference in
      the phenotype of their tracheal systems. 

PMID- 24281355
TI  - Aggregation behaviour and electron injection/recombination dynamics of
      symmetrical and unsymmetrical Zn-phthalocyanines on TiO2 film.
AB  - We have synthesized symmetrical and unsymmetrical Zn-phthalocyanine derivatives
      (PZnPc, MPZnPc and TPZnPc) for dye sensitized solar cells (DSSCs). Steady state
      and time-resolved absorption and fluorescence studies were performed in DMF
      solvent and on a TiO2 surface. The mode and extent of aggregation (H- and J
      aggregates) of ZnPc adsorbed on a TiO2 surface were demonstrated. MPZnPc shows
      both H- and J-aggregation, while TPZnPc shows only H-aggregation. Moreover, the
      fluorescence of ZnP/TiO2 was completely quenched and this was assigned to
      electron injection from excited ZnPc to TiO2. Energy level calculations show both
      ZnPc deriviatives have enough driving force to inject electrons into the
      conduction band of TiO2. Furthermore, the radical cation of ZnPc was observed in
      nanosecond transient absorption measurements. 

PMID- 24281353
TI  - Evolution of vertebrate mechanosensory hair cells and inner ears: toward
      identifying stimuli that select mutation driven altered morphologies.
AB  - Among the major distance senses of vertebrates, the ear is unique in its complex
      morphological changes during evolution. Conceivably, these changes enable the ear
      to adapt toward sensing various physically well-characterized stimuli. This
      review develops a scenario that integrates sensory cell with organ evolution. We
      propose that molecular and cellular evolution of the vertebrate hair cells
      occurred prior to the formation of the vertebrate ear. We previously proposed
      that the genes driving hair cell differentiation were aggregated in the otic
      region through developmental re-patterning that generated a unique vertebrate
      embryonic structure, the otic placode. In agreement with the presence of
      graviceptive receptors in many vertebrate outgroups, it is likely that the
      vertebrate ear originally functioned as a simple gravity-sensing organ. Based on
      the rare occurrence of angular acceleration receptors in vertebrate outgroups, we
      further propose that the canal system evolved with a more sophisticated ear
      morphogenesis. This evolving morphogenesis obviously turned the initial otocyst
      into a complex set of canals and recesses, harboring multiple sensory epithelia
      each adapted to the acquisition of a specific aspect of a given physical
      stimulus. As support for this evolutionary progression, we provide several
      details of the molecular basis of ear development. 

PMID- 24281356
TI  - Amplitude spectrum EEG signal evidence for the dissociation of motor and
      perceptual spatial working memory in the human brain.
AB  - This study investigated the question whether spatial working memory related to
      movement plans (motor working memory) and spatial working memory related to
      spatial attention and perceptual processes (perceptual spatial working memory)
      share the same neurophysiological substrate or there is evidence for separate
      motor and perceptual working memory streams of processing. Towards this aim, ten
      healthy human subjects performed delayed responses to visual targets presented at
      different spatial locations. Two tasks were attained, one in which the spatial
      location of the target was the goal for a pointing movement and one in which the
      spatial location of the target was used for a perceptual (yes or no) change
      detection. Each task involved two conditions: a memory condition in which the
      target remained visible only for the first 250 ms of the delay period and a delay
      condition in which the target location remained visible throughout the delay
      period. The amplitude spectrum analysis of the EEG revealed that the alpha (8-12
      Hz) band signal was smaller, while the beta (13-30 Hz) and gamma (30-45 Hz) band
      signals were larger in the memory compared to the non-memory condition. The alpha
      band signal difference was confined to the frontal midline area; the beta band
      signal difference extended over the right hemisphere and midline central area,
      and the gamma band signal difference was confined to the right occipitoparietal
      area. Importantly, both in beta and gamma bands, we observed a significant
      increase in the movement-related compared to the perceptual-related memory
      specific amplitude spectrum signal in the central midline area. This result
      provides clear evidence for the dissociation of motor and perceptual spatial
      working memory.

PMID- 24281357
TI  - Stationary distribution of self-organized states and biological information
      generation.
AB  - Self-organization, where spontaneous orderings occur under driven conditions, is
      one of the hallmarks of biological systems. We consider a statistical mechanical
      treatment of the biased distribution of such organized states, which become
      favored as a result of their catalytic activity under chemical driving forces. A
      generalization of the equilibrium canonical distribution describes the stationary
      state, which can be used to model shifts in conformational ensembles sampled by
      an enzyme in working conditions. The basic idea is applied to the process of
      biological information generation from random sequences of heteropolymers, where
      unfavorable Shannon entropy is overcome by the catalytic activities of selected
      genes. The ordering process is demonstrated with the genetic distance to a
      genotype with high catalytic activity as an order parameter. The resulting free
      energy can have multiple minima, corresponding to disordered and organized phases
      with first-order transitions between them. 

PMID- 24281358
TI  - Application of Raman spectroscopy for visualizing biochemical changes during
      peripheral nerve injury in vitro and in vivo.
AB  - Raman spectroscopy can be used for analysis of objects by detecting the
      vibrational spectrum using label-free methods. This imaging method was applied to
      analysis of peripheral nerve regeneration by examining the sciatic nerve in vitro
      and in vivo. Raman spectra of intact nerve tissue had three particularly
      important peaks in the range 2800-3000 cm-1. Spectra of injured sciatic nerves
      showed significant changes in the ratio of these peaks. Analysis of cellular
      spectra suggested that the spectrum for sciatic nerve tissue reflects the axon
      and myelin components of this tissue. Immunohistochemical analysis showed that
      the number of axons and the myelinated area were reduced at 7 days after injury
      and then increased by 28 days. The relative change in the axon to myelin ratio
      showed a similar initial increase, followed by a decrease at 28 days after
      injury. These changes correlated with the band intensity ratio and the changes in
      distribution of axon and myelin in Raman spectral analysis. Thus, our results
      suggest that label-free biochemical imaging with Raman spectroscopy can be used
      to detect turnover of axon and myelin in peripheral nerve regeneration.

PMID- 24281359
TI  - Ocular and visual status among children in special schools in Wales: the burden
      of unrecognised visual impairment.
AB  - BACKGROUND/AIMS: The high prevalence of visual defects among children with
      special needs is well reported and guidelines for vision screening are in place.
      However, recent research has suggested that vision care for such children is
      neglected. This study set out to evaluate the current status of vision screening
      and eye care in special schools in Wales. METHODS: In phase 1, all 44 special
      schools in Wales received a questionnaire on current vision screening practices.
      In phase 2, full eye examinations were conducted with 173 pupils of five schools
      with no screening service; the pupils were aged 2-21 years. In phase 3, feedback
      about the service was obtained from all schools and from 15 parents whose
      children took part. RESULTS: In phase 1, vision screening was patchy and
      inconsistent among the 39 schools responding. In phase 2, there is a high
      proportion of pupils (42%) reporting no previous eye examination. Overall, 17% of
      the pupils in the five schools presented with low vision (WHO definition, poorer
      than 0.3 LogMAR), 50% needed a first-time or updated spectacle prescription and
      51% had some ocular abnormality that was either sight-limiting or warranted
      action to prevent risk to sight. In phase 3, school staff and parents reported
      that school-based eye examinations were valuable and, for those children with
      previous experience, likely to be more successful than clinic-based or practice
      based examinations for this particular population. CONCLUSIONS: There is an
      urgent need for a school-based optometric service for this vulnerable group of
      children and young people.

PMID- 24281363
TI  - Different risk factor profiles between transient global amnesia and transient
      ischemic attack: a large case-control study.
AB  - BACKGROUND: The pathophysiology of transient global amnesia (TGA) is not fully
      understood. This study was conducted to identify the cardiovascular risk factors
      of TGA compared to those of transient ischemic attack (TIA) and normal controls,
      using a large number of subjects. In addition to the comparison of risk factors,
      an association between the observed cardiovascular risk factors in the current
      study and a pathophysiological mechanism recently investigated was speculated
      upon. MATERIALS AND METHODS: We performed a retrospective case-control study that
      compared 293 TGA patients to 632 TIA patients and 293 age- and sex-matched normal
      controls. Demographic details and cardiovascular risk factors were carefully
      recorded. RESULTS: TGA patients had a significantly higher prevalence of ischemic
      heart disease and hyperlipidemia; however, they had a lower prevalence of
      hypertension, diabetes mellitus, ischemic stroke and atrial fibrillation when
      compared to TIA patients. When compared to age- and sex-matched normal controls,
      TGA patients also had a significantly higher prevalence of hyperlipidemia,
      previous ischemic stroke and ischemic heart disease. CONCLUSION: The
      cardiovascular risk factors identified in TGA patients in this study were
      different from those of previously reported studies. This disproportionate
      prevalence of cardiovascular risk factors may constitute possible evidence that
      TGA and TIA differ in their pathophysiological mechanism. In addition, some
      cardiovascular risk factors, such as hyperlipidemia and ischemic heart disease,
      should be regarded as possible risk factors of TGA.

PMID- 24281360
TI  - Association of linear IgA bullous disease with ulcerative colitis: a case of
      successful treatment with infliximab.
AB  - Linear IgA bullous disease (LABD) has been reported in association with
      inflammatory bowel disease, in particular ulcerative colitis (UC). We reporting a
      34-year-old female who developed LABD during a flare-up of UC. We administered
      infliximab, which has been approved for the treatment of UC; infliximab
      dramatically improved the cutaneous lesions and bowel symptoms. This is the first
      report showing a marked effect of infliximab on LABD. First, we hypothesize that
      infliximab works for UC and then calms down excessive production of inflammatory
      cytokines and autoantibodies, and so stricter control of UC by infliximab is
      beneficial against the skin condition of LABD. Second, we suggest that TNF-alpha
      production in the lesion of LABD is increased, so TNF-alpha plays an important
      role in developing cutaneous lesions. This case suggests that infliximab, a
      monoclonal antibody against TNF-alpha, is efficacious in the cutaneous symptoms
      of LABD.

PMID- 24281361
TI  - The effectiveness of cognitive remediation therapy in patients with a severe or
      enduring eating disorder: a randomized controlled trial.
AB  - BACKGROUND: Individuals with eating disorders show deficits in neuropsychological
      functioning which might preexist and underlie the etiology of the eating
      disorders and influence relapse. Deficits in cognitive flexibility, i.e., set
      shifting and central coherence, might perpetuate the symptoms. Cognitive
      remediation therapy (CRT) was developed to improve cognitive flexibility, thereby
      increasing the likelihood of improved outcome. The focus of CRT is on how
      patients think, rather than on what patients think. The present study
      investigated the effectiveness of CRT for patients with a severe or enduring
      eating disorder by means of a randomized controlled trial comparing intensive
      treatment as usual (TAU) to CRT plus TAU. METHODS: Eighty-two patients were
      randomly assigned to CRT plus TAU (n = 41) or TAU alone (n = 41). Outcome
      measures were set-shifting, central coherence, eating disorder and general
      psychopathology, motivation, quality of life and self-esteem. Assessments were
      performed at baseline (n = 82) and after 6 weeks (T1; n = 75) and 6 months (T2; n
      = 67). Data were analyzed by means of linear mixed model analyses. RESULTS:
      Patients who received CRT in addition to TAU improved significantly more with
      regard to eating disorder-related quality of life at the end of treatment (T1)
      and eating disorder psychopathology at follow-up (T2), compared to those who
      received TAU only. Moreover, moderator analyses revealed that patients with poor
      baseline set-shifting abilities benefited more from CRT than patients with no
      deficits in set-shifting abilities at baseline; the quality of life of the former
      group was higher than that of the latter at follow-up. CONCLUSIONS: CRT seems to
      be promising in enhancing the effectiveness of concurrent treatment.

PMID- 24281365
TI  - Retrieving Y chromosomal haplogroup trees using GWAS data.
AB  - Phylogenetically informative Y chromosomal single-nucleotide polymorphisms (Y
      SNPs) integrated in DNA chips have not been sufficiently explored in most genome
      wide association studies (GWAS). Herein, we introduce a pipeline to retrieve Y
      SNP data. We introduce the software YTool (http://mitotool.org/ytool/) to handle
      conversion, filtering, and annotation of the data. Genome-wide SNP data from
      populations in Myanmar are used to construct a haplogroup tree for 117 Y
      chromosomes based on 369 high-confidence Y-SNPs. Parallel genotyping and
      published resequencing data of Y chromosomes confirm the validity of our
      pipeline. We apply this strategy to the CEU HapMap data set and construct a
      haplogroup tree with 107 Y-SNPs from 39 individuals. The retrieved Y-SNPs can
      discern the parental genetic structure of populations. Given the massive quantity
      of data from GWAS, this method facilitates future investigations of Y chromosome
      diversity. 

PMID- 24281364
TI  - BRCA1/2 mutations and FMR1 alleles are randomly distributed: a case control
      study.
AB  - BRCA mutation carriers were reported to display a skewed distribution of FMR1
      genotypes, predominantly within the low normal range (CGG repeat number <26).
      This observation led to the interpretation that BRCA1/2 mutations are embryo
      lethal, unless rescued by 'low FMR1 alleles'. We undertook to re-explore the
      distribution of FMR1 alleles subdivided into low, normal and high (<26, 26-34,
      and >34 CGG repeats, respectively) subgenotypes, on a cohort of 125 Ashkenazi
      women, carriers of a BRCA1/2 founder mutation. Ashkenazi healthy females (n=368),
      tested in the frame of the Israeli screening population program, served as
      controls. BRCA1/2 carriers and controls demonstrated a comparable and non-skewed
      FMR1 subgenotype distribution. Taken together, using a homogeneous ethnic group
      of Ashkenazi BRCA1/2 mutation carriers, we could not confirm the reported
      association between FMR1 low genotypes and BRCA1/2 mutations. The notion that
      BRCA1/2 mutations are embryo-lethal unless rescued by the low FMR1 subgenotypes
      is hereby refuted. 

PMID- 24281366
TI  - Exome sequencing in developmental eye disease leads to identification of causal
      variants in GJA8, CRYGC, PAX6 and CYP1B1.
AB  - Developmental eye diseases, including cataract/microcornea, Peters anomaly and
      coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many
      different signalling and structural proteins in the developing eye. All modes of
      Mendelian inheritance occur and many are sporadic cases, so provision of accurate
      recurrence risk information for families and affected individuals is highly
      challenging. Extreme genetic heterogeneity renders testing for all known disease
      genes clinically unavailable with traditional methods. We used whole-exome
      sequencing in 11 unrelated developmental eye disease patients, as it provides a
      strategy for assessment of multiple disease genes simultaneously. We identified
      five causative variants in four patients in four different disease genes, GJA8,
      CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients
      where clinical testing is frequently not undertaken due to lack of availability
      and cost. The results affected clinical management in all cases. These variants
      were detected in the cataract/microcornea and Peters anomaly patients. In two
      patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified
      with incomplete penetrance, highlighting the complex inheritance pattern
      associated with this phenotype. In the coloboma/microphthalmia patients, four
      other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene
      to be considered as a modifier in coloboma/microphthalmia. 

PMID- 24281367
TI  - Microcephaly with or without chorioretinopathy, lymphoedema, or mental
      retardation (MCLMR): review of phenotype associated with KIF11 mutations.
AB  - Microcephaly with or without chorioretinopathy, lymphoedema, or mental
      retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for
      which a causative gene has recently been identified. Mutations in the kinesin
      family member 11 (KIF11) gene have now been described in 16 families worldwide.
      This is a review of the condition based on the clinical features of 37
      individuals from 22 families. This report includes nine previously unreported
      families and additional information for some of those reported previously. The
      condition arose de novo in 8/20 families (40%). The parental results were not
      available for two probands. The mutations were varied and include missense,
      nonsense, frameshift, and splice site and are distributed evenly throughout the
      KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality
      consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate
      learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We
      identified three individuals with KIF11 mutations but no clinical features of
      MCLMR demonstrating reduced penetrance. The variable expression of the phenotype
      and the presence of mildly affected individuals indicates that the prevalence may
      be higher than expected, and we would therefore recommend a low threshold for
      genetic testing. 

PMID- 24281368
TI  - Deleterious mutation in FDX1L gene is associated with a novel mitochondrial
      muscle myopathy.
AB  - Isolated metabolic myopathies encompass a heterogeneous group of disorders, with
      mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy
      production manifesting either by recurrent episodes of myoglobinuria or
      progressive muscle weakness. In this study, we investigated the genetic cause of
      a patient from a consanguineous family who presented with adolescent onset
      autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the
      five respiratory chain complexes in our patients' skeletal muscle showed severely
      impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and
      mitochondrial aconitase. We employed exome sequencing combined with homozygosity
      mapping to identify a homozygous mutation, c.1A>T, in the FDX1L gene, which
      encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the
      ATG initiation translation site resulting in severe reduction of Fdx2 content in
      the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of
      the Fe-S cluster biogenesis machinery, the first being IscU that is associated
      with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L
      in cases of mitochondrial myopathy especially when associated with reduced
      activity of the respiratory chain complexes I, II and III. 

PMID- 24281369
TI  - Structural genomic variation in childhood epilepsies with complex phenotypes.
AB  - A genetic contribution to a broad range of epilepsies has been postulated, and
      particularly copy number variations (CNVs) have emerged as significant genetic
      risk factors. However, the role of CNVs in patients with epilepsies with complex
      phenotypes is not known. Therefore, we investigated the role of CNVs in patients
      with unclassified epilepsies and complex phenotypes. A total of 222 patients from
      three European countries, including patients with structural lesions on magnetic
      resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies,
      were clinically evaluated and screened for CNVs. MRI findings including acquired
      or developmental lesions and patient characteristics were subdivided and analyzed
      in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had
      abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222
      patients (31.9%). Segregation of all identified variants could be assessed in 42
      patients, 11 of which were de novo. The frequency of all structural variants and
      de novo variants was not statistically different between patients with or without
      MRI abnormalities or MRI subcategories. Patients with dysmorphic features were
      more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may
      provide clues for the genetic etiology in patients with a broader range of
      epilepsies than previously anticipated, including in patients with various brain
      anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be
      a valuable contribution to the routine diagnostic workup in patients with a broad
      range of childhood epilepsies. 

PMID- 24281370
TI  - Genealogical analysis as a new approach for the investigation of drug intolerance
      heritability.
AB  - Genealogical analysis has proven a useful method to understand the origins and
      frequencies of hereditary diseases in many populations. However, this type of
      analysis has not yet been used for the investigation of drug intolerance among
      patients suffering from inherited disorders. This study aims to do so, using data
      from familial hypercholesterolemia (FH) patients receiving high doses of statins.
      The objective is to measure and compare various genealogical parameters that
      could shed light on the origins and heritability of muscular intolerance to
      statins using FH as a model. Analysis was performed on 224 genealogies from 112
      FH subjects carrying either the low-density lipoprotein receptor (LDLR) prom_e1
      deletion>15 kb (n=28) or c.259T>G (p.Trp87Gly) (n=84) mutations and 112 non-FH
      controls. Number of ancestors, geographical origins and genetic contribution of
      founders, inbreeding and kinship coefficients were calculated using the S-Plus
      based GENLIB software package. For both mutations, repeated occurrences of the
      same ancestors are more frequent among the carriers' genealogies than among the
      controls', but no difference was observed between tolerant and intolerant
      subjects. Founders who may have introduced both mutations in the population
      appear with approximately the same frequencies in all genealogies. Kinship
      coefficients are higher among carriers, with no difference according to statins
      tolerance. Inbreeding coefficients are slightly lower among >15-kb deletion
      carriers than among c.259 T>G carriers, but the differences between tolerants and
      intolerants are not significant. These findings suggest that although muscular
      intolerance to statins shows a family aggregation, it is not transmitted through
      the same Mendelian pattern as LDLR mutations. 

PMID- 24281371
TI  - Research participants' attitudes towards the confidentiality of genomic sequence
      information.
AB  - Respecting the confidentiality of personal data contributed to genomic studies is
      an important issue for researchers using genomic sequencing in humans. Although
      most studies adhere to rules of confidentiality, there are different conceptions
      of confidentiality and why it is important. The resulting ambiguity obscures what
      is at stake when making tradeoffs between data protection and other goals in
      research, such as transparency, reciprocity, and public benefit. Few studies have
      examined why participants in genomic research care about how their information is
      used. To explore this topic, we conducted semi-structured phone interviews with
      30 participants in two National Institutes of Health research protocols using
      genomic sequencing. Our results show that research participants value
      confidentiality as a form of control over information about themselves. To the
      individuals we interviewed, control was valued as a safeguard against
      discrimination in a climate of uncertainty about future uses of individual genome
      data. Attitudes towards data sharing were related to the goals of research and
      details of participants' personal lives. Expectations of confidentiality, trust
      in researchers, and a desire to advance science were common reasons for
      willingness to share identifiable data with investigators. Nearly, all
      participants were comfortable sharing personal data that had been de-identified.
      These findings suggest that views about confidentiality and data sharing are
      highly nuanced and are related to the perceived benefits of joining a research
      study. 

PMID- 24281373
TI  - Frailty: role of nutrition and exercise.
AB  - PURPOSE OF REVIEW: The scope of the current study is to provide an updated,
      comprehensive review of the recent literature (past 12 months), examining the
      role of nutrition and exercise on frailty. RECENT FINDINGS: Over the past 12
      months, seven studies with different designs explored the relationship between
      nutrition and frailty, four examined the role of exercise on frailty, and only
      one study investigated the combination of the two interventions. The only study
      combining an exercise program with a nutritional consultation reported a short
      term (3 months) improvement of the frailty status. Nevertheless, this study (a
      feasibility pilot trial) was characterized by a relatively small sample size, low
      response rates, and poor compliance. Notably, available evidence shows
      considerable variability in participants' selection, assessment methods, and
      outcomes of interest, so it is difficult to draw direct comparisons. Size effects
      or magnitude of associations across the different studies cannot also be
      determined. SUMMARY: The present findings suggest the need of long-term,
      adequately powered, randomized controlled trials testing nutrition, exercise or
      both interventions for the treatment of frailty in the elders. Such evidence will
      greatly support the future design of preventive strategies against disability in
      older persons.

PMID- 24281372
TI  - Phenotypes of craniofrontonasal syndrome in patients with a pathogenic mutation
      in EFNB1.
AB  - Craniofrontonasal syndrome (CFNS) is an X-linked developmental malformation,
      caused by mutations in the EFNB1 gene, which have only been described since 2004.
      A genotype-phenotype correlation seems not to be present. As it is of major
      importance to adequately counsel patients with EFNB1 mutations and their parents,
      and to improve diagnosis of new patients, more information about the phenotypic
      features is needed. This study included 23 patients (2 male, 21 female) with
      confirmed EFNB1 mutations. All patients underwent a thorough physical examination
      and photographs were taken. If available, radiological images were also
      consulted. Hypertelorism, longitudinal ridging and/or splitting of nails, a
      (mild) webbed neck and a clinodactyly of one or more toes were the only
      consistent features observed in all patients. Frequently observed phenotypic
      features were bifid tip of the nose (91%), columellar indentation (91%) and low
      implantation of breasts (90%). In comparison with anthropometric data of facial
      proportions, patients with CFNS had a significantly different face in multiple
      respects. An overview of all phenotypic features is shown. Patients with EFNB1
      mutations have a clear phenotype. This study will facilitate genetic counseling
      of parents and patients, and contribute to the diagnostic and screening process
      of patients with suspected CFNS. 

PMID- 24281374
TI  - Glutamine in the intensive care unit.
AB  - PURPOSE OF REVIEW: To analyze the recent literature (2011-2013) on glutamine
      supplementation of parenteral and enteral nutrition in critically ill patients.
      Potential confounding factors that may explain conflicting results are suggested.
      RECENT FINDINGS: Some recent, prospective, multicenter trials and two small
      trials yielded conflicting results that weigh heavily in the conclusions of a
      recent meta-analysis. Heterogeneity of the patients enrolled (especially in terms
      of injury severity, age, and basal nutritional status) and difficulties in
      identifying patients truly in need of glutamine supplementation may explain the
      discrepancies. SUMMARY: Glutamine supplementation has been recognized as
      beneficial in acutely injured patients. However, recent conflicting results in
      either 'real-life conditions' or very severe situations suggest that its
      indications need to be more precisely determined.

PMID- 24281375
TI  - Asymmetric dimethylarginine and critical illness.
AB  - PURPOSE OF REVIEW: Asymmetric dimethylarginine (ADMA) is an analog of arginine
      and functions as an endogenous inhibitor of the nitric oxide synthase, which
      forms nitric oxide. Nitric oxide is crucial for perfusion of vital organs and is
      an important signaling agent in the development of critical illness. The role of
      ADMA in the pathophysiological mechanisms underlying critical illness is widely
      studied in the last decades, and recently it has become clear that ADMA should
      not be overlooked by clinicians working at the ICU. The aim of this review is to
      describe new insights into the role of ADMA in critical illness and its clinical
      relevance. RECENT FINDINGS: High levels of ADMA are found in critically ill
      patients, because of higher levels of protein methylation, increased rate of
      protein turnover, decreased activity of dimethylamine dimethylaminohydrolase, and
      impaired renal and hepatic clearance capacity. These high levels are an
      independent risk factor for cardiac dysfunction, organ failure, and ICU
      mortality. The arginine : ADMA ratio in particular is of clinical importance and
      the restoration of this ratio is expedient to restore several functions that are
      disturbed during critical illness. SUMMARY: Elevated ADMA levels occur in
      critically ill patients, which is detrimental for morbidity and mortality. The
      arginine : ADMA ratio should be restored to maintain nitric oxide production and
      therewith improve the clinical outcome of the patient.

PMID- 24281376
TI  - Treatment of hyperammonemia in liver failure.
AB  - PURPOSE OF REVIEW: Hyperammonemia is thought to be central in the pathophysiology
      of hepatic encephalopathy in patients suffering from liver failure. The purpose
      of this article is to explore existing treatment options that help lower ammonia
      levels in patients and alleviate symptoms of hepatic encephalopathy. RECENT
      FINDINGS: There are two ways to approach modulating ammonia levels and its effect
      on the brain. The first targets ammonia levels itself and the second targets
      inflammation, which makes the brain susceptible to the deleterious effect of
      ammonia. Recent studies provide new evidence for the use of lactulose, probiotics
      and rifaximin, as well as closure of large portosystemic shunts in the treatment
      of hepatic encephalopathy. SUMMARY: Over the past 20 years or so, many new
      approaches to treat hepatic encephalopathy have been developed based upon better
      understanding of interorgan ammonia metabolism. Reduction in ammonia can be
      achieved by targeting its production, absorption or elimination. This review will
      primarily focus on these strategies that reduce ammonia levels in liver failure
      patients.

PMID- 24281377
TI  - Exercise, nutrition and managing hip fracture in older persons.
AB  - PURPOSE OF REVIEW: Lifestyle factors play a role in both the genesis and recovery
      from fragility fracture. The purpose of this review is to summarize recent
      evidence for exercise and nutrition in the management of hip fracture. RECENT
      FINDINGS: Recent randomized controlled trials of exercise have primarily
      consisted of isolated resistance training or multimodal home-based programs. More
      robust, long-term, or supervised training is generally associated with greater
      clinical benefits, including muscle strength, mobility, and function. Recent
      nutritional interventions have included multinutrient supplements, nutritional
      counseling and support, and vitamin D/calcium supplementation. Isolated
      nutritional interventions have not consistently shown significant impact on long
      term outcomes after hip fracture, although improvements in body weight,
      biochemical indices, complication rates, and mobility have been reported.
      Overall, there is marked heterogeneity in the robustness of responses seen to hip
      fracture treatment studies. Few large, long-term, multicomponent interventions
      with clinically relevant outcomes of functional independence, need for
      residential care, mortality, and quality of life have been reported. SUMMARY:
      Evidence-based approaches to hip fracture should include comprehensive risk
      factor assessment and treatment for sarcopenia/dynapenia, balance impairment,
      undernutrition of protein, energy, vitamin D and calcium, depression, cognitive
      impairment, sensory impairment, social isolation, and comorbid illness with
      exercise, nutrition and other modalities.

PMID- 24281379
TI  - Effect of co-administration of rivaroxaban and clopidogrel on bleeding time,
      pharmacodynamics and pharmacokinetics: a phase I study.
AB  - Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as
      clopidogrel, is effective for the secondary prevention of cardiovascular events
      in patients with acute coronary syndrome, but there is still a substantial
      residual risk of recurrence. Although anticoagulant therapy with a vitamin K
      antagonist (e.g. warfarin) in conjunction with antiplatelet therapy has been
      shown to reduce the risk of cardiovascular events, the rates of bleeding were
      increased with these combination therapies; hence, triple therapy with warfarin
      is currently only recommended in patients at low risk of bleeding. In addition,
      there are other limitations associated with vitamin K antagonist therapy,
      including the need for routine coagulation monitoring and dose adjustment to
      maintain the treatment within the therapeutic range. Rivaroxaban is an oral,
      direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban
      will be given to patients who also receive antiplatelet therapy, such as
      clopidogrel. This randomized, non-blinded, three-way crossover study investigated
      the effect of rivaroxaban on bleeding time when co-administered with clopidogrel.
      In addition, the influence of clopidogrel on the safety, tolerability,
      pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27
      healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were
      identified as clopidogrel responders and were then randomized to the following
      three treatments: (A) two doses of clopidogrel on two consecutive days (300 mg on
      day 1; 75 mg on day 2); (B) one dose of rivaroxaban (15 mg); or (C) a combination
      of treatments A and B (rivaroxaban given on day 2). All treatments were well
      tolerated. Bleeding time with co-administration of rivaroxaban and clopidogrel
      was significantly prolonged in four subjects, compared with either drug alone:
      combination treatment increased the overall least squares-means to 3.77 times
      baseline (90% confidence interval [CI] 2.82-4.73), compared with 1.13 times
      baseline (90% CI 0.17-2.09) with rivaroxaban and 1.96 times baseline (90% CI 0.10
      2.91) with clopidogrel. Co-administration of clopidogrel had no significant
      effect on the pharmacokinetics of rivaroxaban and, when compared with rivaroxaban
      alone, had no further effects on Factor Xa activity or prothrombin time.
      Inhibition of ADP-stimulated platelet aggregation by clopidogrel was not affected
      by rivaroxaban. As expected, owing to the mode of action of each study drug, the
      results of this study demonstrated that co-administration of the Factor Xa
      inhibitor rivaroxaban and the antiplatelet clopidogrel increased the bleeding
      time in healthy subjects without affecting other pharmacokinetic or
      pharmacodynamic parameters of each drug. 

PMID- 24281380
TI  - Heterocycles in peptidomimetics and pseudopeptides: design and synthesis.
AB  - This minireview provides a brief outline of the peculiar aspects of the
      preparation of peptidomimetic and pseudopeptidic structures containing
      heterocycles. In particular novel tricyclic structures are investigated as
      potential drugs. 

PMID- 24281381
TI  - Pyrazole carbohydrazide derivatives of pharmaceutical interest.
AB  - The main purpose of this paper is to provide an insight into the biological
      activities of pyrazole derivatives which contain the carbohydrazide moiety. 

PMID- 24281378
TI  - Receptor and channel heteromers as pain targets.
AB  - Recent discoveries indicate that many G-protein coupled receptors (GPCRs) and
      channels involved in pain modulation are able to form receptor heteromers.
      Receptor and channel heteromers often display distinct signaling characteristics,
      pharmacological properties and physiological function in comparison to
      monomer/homomer receptor or ion channel counterparts. It may be possible to
      capitalize on such unique properties to augment therapeutic efficacy while
      minimizing side effects. For example, drugs specifically targeting heteromers may
      have greater tissue specificity and analgesic efficacy. This review will focus on
      current progress in our understanding of roles of heteromeric GPCRs and channels
      in pain pathways as well as strategies for controlling pain pathways via
      targeting heteromeric receptors and channels. This approach may be instrumental
      in the discovery of novel classes of drugs and expand our repertoire of targets
      for pain pharmacotherapy. 

PMID- 24281382
TI  - Comparison of intraocular pressure, blood pressure, ocular perfusion pressure and
      blood flow fluctuations during dorzolamide versus timolol add-on therapy in
      prostaglandin analogue treated glaucoma subjects.
AB  - OBJECTIVE: To compare the effects of dorzolamide and timolol add-on therapy in
      open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue
      (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular
      perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. METHODS:
      35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated
      in a 3 month randomized, cross-over, single-masked study. During the experiments
      BP, heart rate, IOP and OPP were assessed 4 times per day (8-12-16-20 h). RBF was
      measured twice per day (8-20 h) using Color Doppler imaging in the ophthalmic
      (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary
      arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity
      (EDV) were assessed and vascular resistance (RI) calculated. RESULTS: Both add-on
      therapies lowered IOP in a statistically significant manner from 15.7 +/- 2.4
      mmHg at latanoprost baseline to 14.9 +/- 2.2 mmHg using dorzolamide (p < 0.001)
      and 14.2 +/- 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was
      statistically significant at 20 h, favoring timolol as compared to dorzolamide
      (1.4 +/- 2.4 vs. 0.2 +/- 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed
      smaller IOP (2.0 +/- 1.4), SPP (13.3 +/- 7.9), systolic BP (13.5 +/- 8.7) and
      diastolic BP (8.4 +/- 5.4) fluctuations as compared to both latanoprost baseline
      or timolol add-on therapies. Higher difference between morning and evening BP was
      correlated to decreased evening CRA EDV in the timolol group (c = -0.41; p =
      0.01). With increased MAP in the morning or evening hours, we found increased
      evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002
      accordingly). Higher MAP fluctuations were related to impaired RBF parameters
      during evening hours-decreased CRA EDV (c = -0.408; p = 0.01), increased CRA RI
      (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide
      group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group.
      OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the
      timolol group. OPP fluctuations were not related to IOP fluctuations in both add
      on therapies (p < 0.05). CONCLUSIONS: Both dorzolamide and timolol add-on
      therapies lowered IOP in a statistically significant fashion dorzolamide add-on
      therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of
      daytime OPP led to impaired RBF parameters in the evening.

PMID- 24281384
TI  - Optimization of a genetically encoded biosensor for cyclin B1-cyclin dependent
      kinase 1.
AB  - Fluorescent protein (FP)-based biosensors have revolutionized the ability of
      researchers to monitor enzyme activities in live cells. While the basic design
      principles for FP-based biosensors are well established, first-generation
      biosensor constructs typically suffer from relatively low fluorescence responses
      that limit their general applicability. The protein engineering efforts required
      to substantially improve the biosensor responses are often both labour and time
      intensive. Here we report the application of a high throughput bacterial colony
      screen for improving the response of kinase biosensors. This effort led to the
      development of a second-generation cyclin B1-CDK1 biosensor with a 4.5-fold
      greater response than the first-generation biosensor. 

PMID- 24281383
TI  - Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic
      inhibition.
AB  - Alcohol dependence is a common, complex and debilitating disorder with genetic
      and environmental influences. Here we show that alcohol consumption increases
      following mutations to the gamma-aminobutyric acidA receptor (GABAAR) beta1
      subunit gene (Gabrb1). Using N-ethyl-N-nitrosourea mutagenesis on an alcohol
      averse background (F1 BALB/cAnN x C3H/HeH), we develop a mouse model exhibiting
      strong heritable preference for ethanol resulting from a dominant mutation
      (L285R) in Gabrb1. The mutation causes spontaneous GABA ion channel opening and
      increases GABA sensitivity of recombinant GABAARs, coupled to increased tonic
      currents in the nucleus accumbens, a region long-associated with alcohol reward.
      Mutant mice work harder to obtain ethanol, and are more sensitive to alcohol
      intoxication. Another spontaneous mutation (P228H) in Gabrb1 also causes high
      ethanol consumption accompanied by spontaneous GABA ion channel opening and
      increased accumbal tonic current. Our results provide a new and important link
      between GABAAR function and increased alcohol consumption that could underlie
      some forms of alcohol abuse. 

PMID- 24281386
TI  - Susceptibility-weighted MR imaging of radiation therapy-induced cerebral
      microbleeds in patients with glioma: a comparison between 3T and 7T.
AB  - INTRODUCTION: Cerebral microbleeds have been observed in normal-appearing brain
      tissue of patients with glioma years after receiving radiation therapy. The
      contrast of these paramagnetic lesions varies with field strength due to
      differences in the effects of susceptibility. The purpose of this study was to
      compare 3T and 7T MRI as platforms for detecting cerebral microbleeds in patients
      treated with radiotherapy using susceptibility-weighted imaging (SWI). METHODS:
      SWI was performed with both 3T and 7T MR scanners on ten patients with glioma who
      had received prior radiotherapy. Imaging sequences were optimized to obtain data
      within a clinically acceptable scan time. Both T2*-weighted magnitude images and
      SWI data were reconstructed, minimum intensity projection was implemented, and
      microbleeds were manually identified. The number of microbleeds was counted and
      compared among datasets. RESULTS: Significantly more microbleeds were identified
      on SWI than magnitude images at both 7T (p = 0.002) and 3T (p = 0.023). Seven
      tesla SWI detected significantly more microbleeds than 3T SWI for seven out of
      ten patients who had tumors located remote from deep brain regions (p = 0.016),
      but when the additional three patients with more inferior tumors were included,
      the difference was not significant. CONCLUSION: SWI is more sensitive for
      detecting microbleeds than magnitude images at both 3T and 7T. For areas without
      heightened susceptibility artifacts, 7T SWI is more sensitive to detecting
      radiation therapy-induced microbleeds than 3T SWI. Tumor location should be
      considered in conjunction with field strength when selecting the most appropriate
      strategy for imaging microbleeds.

PMID- 24281385
TI  - Dissociation of hyperglycemia from altered vascular contraction and relaxation
      mechanisms in caveolin-1 null mice.
AB  - Hyperglycemia and endothelial dysfunction are associated with hypertension, but
      the specific causality and genetic underpinning are unclear. Caveolin-1 (cav-1)
      is a plasmalemmal anchoring protein and modulator of vascular function and
      glucose homeostasis. Cav-1 gene variants are associated with reduced insulin
      sensitivity in hypertensive individuals, and cav-1(-/-) mice show endothelial
      dysfunction, hyperglycemia, and increased blood pressure (BP). On the other hand,
      insulin-sensitizing therapy with metformin may inadequately control hyperglycemia
      while affecting the vascular outcome in certain patients with diabetes. To test
      whether the pressor and vascular changes in cav-1 deficiency states are related
      to hyperglycemia and to assess the vascular mechanisms of metformin under these
      conditions, wild-type (WT) and cav-1(-/-) mice were treated with either placebo
      or metformin (400 mg/kg daily for 21 days). BP and fasting blood glucose were in
      cav-1(-/-) > WT and did not change with metformin. Phenylephrine (Phe)- and KCl
      induced aortic contraction was in cav-1(-/-) < WT; endothelium removal, the
      nitric-oxide synthase (NOS) blocker L-NAME (N(omega)-nitro-L-arginine methyl
      ester), or soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ) enhanced Phe contraction, and metformin blunted this
      effect. Acetylcholine-induced relaxation was in cav-1(-/-) > WT, abolished by
      endothelium removal, L-NAME or ODQ, and reduced with metformin. Nitric oxide
      donor sodium nitroprusside was more potent in inducing relaxation in cav-1(-/-)
      than in WT, and metformin reversed this effect. Aortic eNOS, AMPK, and sGC were
      in cav-1(-/-) > WT, and metformin decreased total and phosphorylated eNOS and
      AMPK in cav-1(-/-). Thus, metformin inhibits both vascular contraction and NO
      cGMP-dependent relaxation but does not affect BP or blood glucose in cav-1(-/-)
      mice, suggesting dissociation of hyperglycemia from altered vascular function in
      cav-1-deficiency states.

PMID- 24281388
TI  - Circulating insulin-like growth factor-binding protein 3 levels, independent of
      insulin-like growth factor 1, associate with truncal fat and systolic blood
      pressure in South Asian and white European preschool children.
AB  - AIMS: To study the effect of the insulin-like growth factor (IGF) system on
      growth, adiposity and systolic blood pressure (SBP) in early life in British-born
      South Asian (SA) and White European (WE) children. METHODS: The effect of IGF-1
      and insulin-like growth factor-binding protein 3 (IGFBP-3) over the first 4 years
      in 204 healthy SA and WE children was investigated by mixed linear regression
      modelling. This enabled inclusion of all follow-up observations and adjustment
      for repeated measures. RESULTS: At birth, SA babies were shorter and lighter than
      WE babies. Over 4 years, SA ethnicity was associated with lower height, weight
      and body mass index (BMI) standard deviation score (SDS), higher
      subscapular/triceps skinfold thickness (Ss/Tr SFT) and lower SBP (all p < 0.01).
      IGF-1 was associated with greater height (p = 0.03), weight (p < 0.001) and BMI
      SDS (p < 0.001), and IGFBP-3 with greater weight SDS (p < 0.001), BMI SDS (p =
      0.001), Ss/Tr SFT (p = 0.003) and SBP (p = 0.023). CONCLUSIONS: Over this first 4
      year period of life, SA ethnicity was associated with being shorter, lighter,
      having more superficial truncal adiposity and lower SBP. IGFBP-3 (and not IGF-1)
      was independently associated with both superficial truncal adiposity and SBP,
      suggesting that IGFBP-3 is a potential metabolic and cardiovascular marker in
      healthy children in the early years of life.

PMID- 24281387
TI  - Is eptifibatide a safe and effective rescue therapy in thromboembolic events
      complicating cerebral aneurysm coil embolization? Single-center experience in 42
      cases and review of the literature.
AB  - INTRODUCTION: Thromboembolic complications are the most frequent perioperative
      complications of endovascular treatment of intracranial aneurysms. Even if the
      effectiveness of glycoprotein IIb/IIIa inhibitors has been reported, the outcomes
      in published clinic data are contradictory. This study aims to assess the
      effectiveness and the safety of eptifibatide in thromboembolic complications
      during intracranial aneurysm embolization procedure. METHODS: Between 2006 and
      2012, 650 patients with intracranial aneurysm were treated using endovascular
      coil embolization, and in 62 cases (9.5 %), an intra-arterial thrombus developed.
      Glycoprotein IIb/IIIa inhibitor was administrated in 45 of them who required a
      rescue treatment. These 45 patients were treated with an intra-arterial bolus
      (0.2 mg/kg) of eptifibatide. We respectively reviewed the angiographic and
      clinical outcomes, and the periprocedural complications of the rescue treatment.
      RESULTS: No intra- or early postoperative (48 h) bleeding was observed after
      treatment. A total recovery of the entire arterial tree (TICI 3) was established
      in 28 cases (62.2 %), a partial revascularization in 13 cases (28.8 %) (5 TICI 2A
      and 8 TICI 2B), and no revascularization or reperfusion (TICI 0 or TICI 1) in 4
      cases (9 %). Eptifibatide was more effective on proximal obstructions and in
      stent occlusions than on peripheral distal thrombus, which were completely
      disintegrated one time out of three. CONCLUSION: Intra-operative intra-arterial
      use of eptifibatide does not imply an increase of hemorrhagic events. Even if
      eptifibatide allows for a high rate of arterial recanalization, its effectiveness
      seems to be less important in cases of distal occlusions.

PMID- 24281390
TI  - Thermal anisotropy in nano-crystalline MoS2 thin films.
AB  - In this work, we grow thin MoS2 films (50-150 nm) uniformly over large areas (>1
      cm(2)) with strong basal plane (002) or edge plane (100) orientations to
      characterize thermal anisotropy. Measurement results are correlated with
      molecular dynamics simulations of thermal transport for perfect and defective
      MoS2 crystals. The correlation between predicted (simulations) and measured
      (experimental) thermal conductivity are attributed to factors such as crystalline
      domain orientation and size, thereby demonstrating the importance of thermal
      boundary scattering in limiting thermal conductivity in nano-crystalline MoS2
      thin films. Furthermore, we demonstrate that the cross-plane thermal conductivity
      of the films is strongly impacted by exposure to ambient humidity. 

PMID- 24281391
TI  - CO2 phonon mode renormalization using phonon-assisted energy up-conversion.
AB  - Molecular dissociation under incident light whose energy is lower than the bond
      dissociation energy has been achieved through multi step excitation using a
      coupled state of a photon, electron, and multimode-coherent phonon as known as
      the dressed photon phonon (DPP). Here, we have investigated the effects of the
      DPP on CO2, a very stable molecule with high absorption and dissociation
      energies, by introducing ZnO nanorods to generate the DPP. Then, the changes in
      CO2 absorption bands were evaluated using light with a wavelength longer than the
      absorption wavelength, which confirmed the DPP-assisted energy up-conversion. To
      evaluate the specific CO2 modes related to this process, we measured the CO2
      vibration-rotation spectra in the near-infrared region. Detailed analysis of the
      3nu3 vibrational band when a DPP source is present showed that DPP causes a
      significant increase in the intensity of certain absorption bands, especially
      those that require higher energies to activate. 

PMID- 24281389
TI  - COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate
      acetylcholinesterase impair the interaction of ColQ with proteins of the basal
      lamina.
AB  - Collagen Q (ColQ) is a key multidomain functional protein of the neuromuscular
      junction (NMJ), crucial for anchoring acetylcholinesterase (AChE) to the basal
      lamina (BL) and accumulating AChE at the NMJ. The attachment of AChE to the BL is
      primarily accomplished by the binding of the ColQ collagen domain to the heparan
      sulfate proteoglycan perlecan and the COOH-terminus to the muscle-specific
      receptor tyrosine kinase (MuSK), which in turn plays a fundamental role in the
      development and maintenance of the NMJ. Yet, the precise mechanism by which ColQ
      anchors AChE at the NMJ remains unknown. We identified five novel mutations at
      the COOH-terminus of ColQ in seven patients from five families affected with
      endplate (EP) AChE deficiency. We found that the mutations do not affect the
      assembly of ColQ with AChE to form asymmetric forms of AChE or impair the
      interaction of ColQ with perlecan. By contrast, all mutations impair in varied
      degree the interaction of ColQ with MuSK as well as basement membrane extract
      (BME) that have no detectable MuSK. Our data confirm that the interaction of ColQ
      to perlecan and MuSK is crucial for anchoring AChE to the NMJ. In addition, the
      identified COOH-terminal mutants not only reduce the interaction of ColQ with
      MuSK, but also diminish the interaction of ColQ with BME. These findings suggest
      that the impaired attachment of COOH-terminal mutants causing EP AChE deficiency
      is in part independent of MuSK, and that the COOH-terminus of ColQ may interact
      with other proteins at the BL. 

PMID- 24281392
TI  - Highly ordered GaN-based nanowire arrays grown on patterned (100) silicon and
      their optical properties.
AB  - Arrays of GaN-based nanowires have been synthesized on patterned silicon without
      a catalyst. The spatial density, length and average radius of the nanowires can
      be well-controlled. The GaN core contains two semipolar facets and a controllable
      polar facet. The nanowire heterostructures exhibit excellent laser behavior. 

PMID- 24281393
TI  - Aldosterone blockade reduces mortality without changing cardiac remodeling in
      spontaneously hypertensive rats.
AB  - BACKGROUND: The role of aldosterone blockers during transition from long-term
      compensated hypertrophy to dilated failure is not completely understood. In this
      study we evaluated the effects of early administration of spironolactone on
      cardiac remodeling, myocardial function, and mortality in spontaneously
      hypertensive rats (SHR). METHODS: Sixteen-month-old SHR received no treatment
      (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months.
      Echocardiogram was performed before and after treatment. Myocardial function was
      analyzed in left ventricular (LV) papillary muscle preparations. Myocardial
      collagen and hydroxyproline concentration were evaluated by morphometry and
      spectrophotometry, respectively. LV gene expression was assessed by real time RT
      PCR. STATISTICS: Student's t test; Log rank test (Kaplan Meyer). RESULTS: SHR-C
      and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004).
      Systolic arterial pressure did not differ between groups (SHR-C 199+/-43; SHR-SPR
      200+/-35 mmHg). Initial and final echocardiograms did not show significant
      differences in cardiac structures or LV function between groups. Myocardial
      function was similar between groups at basal and after inotropic stimulation.
      Collagen fractional area, hydroxyproline concentration, gene expression for alpha
      and beta-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not
      different between groups. CONCLUSION: Early spironolactone administration reduces
      mortality without changing cardiac remodeling in spontaneous hypertensive rats.

PMID- 24281394
TI  - Enhanced production of erythritol by Yarrowia lipolytica on glycerol in repeated
      batch cultures.
AB  - Erythritol is an important natural sweetener, industrially produced only by
      fermentation on glucose media. Glycerol is an important renewable feedstock as it
      is the major by-product of the biodiesel production process; here we present an
      alternative way to convert this low-cost substrate into value-added products,
      such as erythritol. Repeated batch cultures (RBC) were performed to improve the
      productivity of erythritol from pure and crude glycerol. An acetate negative
      mutant of Yarrowia lipolytica Wratislavia K1 was found to be applicable for the
      production of high amounts of erythritol in RBC. When 20 % of fresh replaced
      medium was added, the strain Wratislavia K1 was able to produce 220 g l (-1)
      erythritol, which corresponded to a 0.43 g g(-1) yield and a productivity of 0.54
      g l(-1) h(-1). Additionally, the activity of the culture remained stable for more
      than 1,000 h, i.e., 11 cycles of the repeated batch bioreactors. 

PMID- 24281395
TI  - Design and high-level expression of a hybrid antimicrobial peptide LF15-CA8 in
      Escherichia coli.
AB  - Antimicrobial peptides (AMPs) have been paid considerable attention owing to
      their broad-spectrum antimicrobial activity and have great potential as novel
      antimicrobials. In this study, a novel hybrid peptide LF15-CA8 was designed on
      the basis of bovine lactoferricin (LfcinB) and cecropin A. The gene segment
      encoding LF15-CA8 was synthesized and cloned into pGEX-4T-BH to form pGEX-4T-LC1
      containing one copy of the LF15-CA8 coding region. A series of recombinant
      vectors containing up to six multiple-copy LF15-CA8 coding regions, i.e., pGEX-4T
      LCn (n = 1-6), were subsequently constructed, and used for transformation in
      Escherichia coli BL21(DE3). After induction with IPTG, pGEX-4T-LC1 and pGEX-4T
      LC2 transformants successfully expressed fusion proteins GST-LF15-CA8 and GST
      (LF15-CA8)2 in the form of inclusion bodies, respectively. The inclusion bodies
      were dissolved and the peptide was successfully released in 70 % formic acid in a
      single step. After purification, about 10.0 mg of the recombinant peptide LF15
      CA8 with purity more than 97 % was obtained from 1 l of bacteria culture of pGEX
      4T-LC2 transformants. LF15-CA8 caused an increase in antibacterial activity
      against Gram-positive bacterium (Staphylococcus aureus ATCC 25923) compared with
      the parent peptides and did not show obvious hemolytic activity against human
      erythrocytes in the range of effective antibacterial concentration. These results
      suggest that the peptide LF15-CA8 could be a promising candidate for therapeutic
      applications, and may lead to a cost-effective solution for the large-scale
      production of AMPs.

PMID- 24281396
TI  - Effectiveness of collaborative stepped care for anxiety disorders in primary
      care: a pragmatic cluster randomised controlled trial.
AB  - BACKGROUND: Collaborative stepped care (CSC) may be an appropriate model to
      provide evidence-based treatment for anxiety disorders in primary care. METHODS:
      In a cluster randomised controlled trial, the effectiveness of CSC compared to
      care as usual (CAU) for adults with panic disorder (PD) or generalised anxiety
      disorder (GAD) in primary care was evaluated. Thirty-one psychiatric nurses who
      provided their services to 43 primary care practices in the Netherlands were
      randomised to deliver CSC (16 psychiatric nurses, 23 practices) or CAU (15
      psychiatric nurses, 20 practices). CSC was provided by the psychiatric nurses
      (care managers) in collaboration with the general practitioner and a consultant
      psychiatrist. The intervention consisted of 3 steps, namely guided self-help,
      cognitive behavioural therapy and antidepressants. Anxiety symptoms were measured
      with the Beck Anxiety Inventory (BAI) at baseline and after 3, 6, 9 and 12
      months. RESULTS: We recruited 180 patients with a DSM-IV diagnosis of PD or GAD,
      of whom 114 received CSC and 66 received usual primary care. On the BAI, CSC was
      superior to CAU [difference in gain scores from baseline to 3 months: -5.11, 95%
      confidence interval (CI) -8.28 to -1.94; 6 months: -4.65, 95% CI -7.93 to -1.38;
      9 months: -5.67, 95% CI -8.97 to -2.36; 12 months: -6.84, 95% CI -10.13 to 
      3.55]. CONCLUSIONS: CSC, with guided self-help as a first step, was more
      effective than CAU for primary care patients with PD or GAD.

PMID- 24281397
TI  - A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in
      mice.
AB  - Diet-induced obesity is a lifestyle-associated medical condition that increases
      the risk of developing cardiovascular disease, type 2 diabetes and certain types
      of cancer. Here we report the design of a closed-loop genetic circuit that
      constantly monitors blood fatty acid levels in the setting of diet-associated
      hyperlipidemia and coordinates reversible and adjustable expression of the
      clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of
      the peroxisome proliferator-activated receptor-alpha onto the phloretin
      responsive repressor TtgR produces a synthetic intracellular lipid-sensing
      receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a
      fatty acid-adjustable manner. Mice with diet-induced obesity in which
      microencapsulated cells engineered for LSR-driven expression of pramlintide are
      implanted show significant reduction in food consumption, blood lipid levels and
      body weight when put on a high-fat diet. Therapeutic designer circuits that
      monitor levels of pathologic metabolites and link these with the tailored
      expression of protein pharmaceuticals may provide new opportunities for the
      treatment of metabolic disorders. 

PMID- 24281398
TI  - Altered small airways in aged mice following neonatal exposure to hyperoxic gas.
AB  - BACKGROUND: Supplemental oxygen is necessary in the respiratory support of very
      preterm infants, but it may contribute to bronchopulmonary dysplasia and an
      increased risk of poor lung function in later life. It is well established that
      hyperoxia can inhibit alveolarization, but effects on the developing conducting
      airways, which are important determinants of lung function, are poorly
      understood. It is possible that prolonged exposure of the immature lung to
      hyperoxic gas alters the development of small conducting airways (bronchioles),
      and that these effects may persist throughout life. OBJECTIVES: To examine the
      effects of neonatal inhalation of hyperoxic gas on the bronchiolar walls in
      adulthood. METHODS: Neonatal mice (C57BL/6J) born at term inhaled 65% O2 from
      birth until postnatal day 7; thereafter, they were raised in room air until 10
      months postnatal age (P10mo), which is advanced adulthood. Age-matched controls
      inhaled room air from birth. We investigated small conducting airways with a
      diameter between 105-310 um. RESULTS: At P10mo, bronchiolar walls of hyperoxia
      exposed mice contained ~18% more smooth muscle than controls (p < 0.05), although
      there was no effect on bronchiolar epithelium or collagen. Neonatal hyperoxia
      resulted in significantly fewer bronchiolar-alveolar attachments at P10mo (p <
      0.05); this was accompanied by persistent simplification of the lung parenchyma,
      as indicated by greater mean linear intercept and less parenchymal tissue (p <
      0.05). CONCLUSIONS: Neonatal exposure to hyperoxia induces remodeling of the
      bronchiolar walls and loss of bronchiolar-alveolar attachments in adulthood, both
      of which could contribute to impaired lung function and airway hyper-reactivity.

PMID- 24281399
TI  - Three cases of corticosteroid therapy triggering ventricular fibrillation in J
      wave syndromes.
AB  - We describe three cases of J-wave syndrome in which ventricular fibrillation (VF)
      was probably induced by corticosteroid therapy. The patients involved were being
      treated with prednisolone for concomitant bronchial asthma. One of the three
      patients had only one episode of VF during her long follow-up period (14 years).
      Two patients had hypokalemia during their VF episodes. Corticosteroids have been
      shown to induce various types of arrhythmia and to modify cardiac potassium
      channels. We discuss the possible association between corticosteroid therapy and
      VF in J-wave syndrome based on the cases we have encountered. 

PMID- 24281400
TI  - The clinical characteristics of sudden cardiac arrest in asymptomatic patients
      with congenital heart disease.
AB  - Sudden cardiac arrest (SCA) is a major cause of death in patients with congenital
      heart disease (CHD). Systemic ventricular dysfunction is a reported risk factor
      for SCA. We retrospectively analyzed the medical records of 46 patients (age >6
      years) who experienced SCA. The following underlying cardiac defects were
      observed: biventricular repair with affected subpulmonary right ventricle (n =
      18, 39 %), biventricular repair with systemic right ventricle and Eisenmenger
      syndrome (n = 6 each, 13 %), Fontan circulation and unrepaired CHD (n = 5 each,
      11 %), and others (n = 6, 13 %). Twenty-one patients (46 %) had no history of
      arrhythmias, and 21 of 43 (49 %) showed systemic ventricular ejection fraction
      >55 %. According to the New York Heart Association classification, 18 patients
      (39 %) were class I and 28 (61 %) were class II/III. SCA occurred at a younger
      age in class I (16 +/- 5 years) than in the other classes (23 +/- 10 years; P =
      0.004). QRS duration was similar between the groups (136 +/- 38 vs. 141 +/- 50
      ms; P not significant). Seven patients in class I (15 % of all SCAs) had no
      history of arrhythmias or features of hemodynamic abnormalities. The proportion
      of patients with biventricular repair and affected subpulmonary right ventricle
      was higher than that of patients with other defects, and the majority of SCA
      patients had more complicated defects than a simple repaired ventricular septal
      defect or an atrial septal defect. No symptoms of heart failure, history of
      arrhythmias, or features of hemodynamic abnormalities were observed in 15 % of
      the patients who experienced SCA. Prolonged QRS duration might be a predictor of
      SCA even in asymptomatic CHD patients. Prevention of SCA in CHD patients may
      require more detailed evaluation than is typically considered necessary. 

PMID- 24281401
TI  - Association between a gene variant near ataxia telangiectasia mutated and
      coronary artery disease in men.
AB  - OBJECTIVE: Type 2 diabetes is accompanied by increased mortality from coronary
      artery disease (CAD), but the mechanisms linking these conditions remain elusive.
      Hence, treatment of hyperglycaemia alone is not sufficient to avoid CAD in
      diabetes. Alternative views suggest that metabolic and vascular diseases share
      unifying cellular defects that could serve as targets for novel therapeutic
      strategies. Recently, a variant [single-nucleotide polymorphism (SNP);
      rs11212617] near the gene for ataxia telangiectasia mutated (ATM) has been
      associated with glycaemic response to metformin. MATERIALS AND METHODS: We
      determined rs11212617 in 240 male patients who underwent elective coronary
      angiography. RESULTS: While the variant was not associated with glucose
      concentrations, the A allele was significantly associated with the presence of
      CAD (chi-square, p = 0.003), as well as with logarithmically transformed
      quantitative CAD indices [severe score (SS): 0.5 (0.4-0.6) vs 0.3 (0.2-0.5);
      extent score (ES): 2.63 (2.4-2.9) vs 1.94 (1.4-2.4), both p < 0.05,
      respectively]. Multivariate analysis revealed an independent association between
      the A allele with ES (beta = 0.17, p < 0.01). CONCLUSION: Our data suggest that
      ATM-dependent signalling might play a role in the development of atherosclerotic
      vascular disease, but larger studies are necessary to substantiate such a
      hypothesis.

PMID- 24281402
TI  - Predicting genetic and ecological characteristics of bacterial species by
      comparing the trajectories of dN/dS and dI/dS in bacterial genomes.
AB  - Indel (insertion/deletion) causes gene disruption and is considered to be
      deleterious like non-synonymous mutation during the evolution of bacterial
      genomes. The trajectory of dN/dS (the ratio of non-synonymous to synonymous
      mutation) has been found to decrease exponentially over time, but the trajectory
      of dI/dS (the ratio of indel to synonymous mutation) has not been thoroughly
      explored yet. Here we compared the patterns of dN/dS and dI/dS for several
      bacterial species. The majority of them showed a much steeper dI/dS trajectory
      than the dN/dS trajectory, suggesting that indel was more deleterious than non
      synonymous mutation and therefore was more difficult to fix in genomes. However,
      the naturally competent bacteria, or those with a much lower genetic barrier for
      DNA exchange, presented a reverse relationship between dI/dS and dN/dS,
      indicative of an exceptional ability to tolerate horizontal genetic transfer. The
      result suggests that plotting of dN/dS and dI/dS trajectories can help to predict
      the genetic and ecological characteristics of bacterial species. 

PMID- 24281403
TI  - Strong improvements of localized surface plasmon resonance sensitivity by using
      Au/Ag bimetallic nanostructures modified with polydopamine films.
AB  - In the present work, the standard monometallic localized surface plasmon
      resonance (LSPR) biosensing sensitivity is highly improved when using a new
      system based on glass substrates modified with high-temperature annealed
      gold/silver bimetallic nanoparticles (Au/Ag bimetallic NPs) coated with
      polydopamine films before biomolecule specific immobilization. Thus, different
      zones of bimetallic NPs are spatially created onto a glass support thanks to a
      commercial transmission electron microscopy (TEM) grid marker in combination with
      two sequential evaporations of continuous films of gold (4 nm) and silver (2 nm)
      and followed by annealing at 500  degrees C for 8 h. By using the scanning
      electron microscopy (SEM), it is found that annealed Au/Ag bimetallic NPs have
      uniform size and shape distribution that exhibited a sharper well-defined LSPR
      resonant peak when compared with that of monometallic Au NPs and thereby
      contributing to an improved sensitivity in LSPR biosensor application. The
      controlled micropatterns consisting of bimetallic particles are used in the
      construction of LSPR biochips for high-throughput detection of different
      concentrations of a model antigen named bovine serum albumin (BSA) on a single
      glass sample, with a lower limit of detection of 0.01 ng/mL under the optimized
      conditions. 

PMID- 24281404
TI  - Existence of ipsilateral hemiparesis in ischemic and hemorrhagic stroke: two case
      reports and review of the literature.
AB  - Supratentorial stroke presenting as contralateral hemiparesis is predominantly
      related to contralateral projection of the corticospinal tract. While most
      corticospinal fibers decussate at the level of the medulla, some tracts continue
      descending as ipsilateral ventral corticospinal fibers. In this systematic review
      of the literature and 2 case reports specifically seen in our institute, we
      describe the presence of ipsilateral hemiparesis in ischemic and hemorrhagic
      stroke patients. We compiled available information about the existence of
      uncrossed corticospinal tracts and/or the presence of bilateral operating motor
      cortical networks. There was an association in patients with congenital uncrossed
      corticospinal tracts and posterior fossa malformations. There was also a high
      correlation of ipsilateral hemiparesis in patients with remote infarction. A
      previous stroke was seen in 50% of the patients, all except for 1 case were
      ischemic in nature. Patients with previous infarcts do demonstrate an adaptive
      compensation for damaged or disconnected regions of an injured area. This
      emphasizes the need to consider the investigation for previous infarctions or
      underlying genetic structural defects by using certain imaging modality.

PMID- 24281405
TI  - Oral Administration of Shark Type II Collagen Suppresses Complete Freund's
      Adjuvant-Induced Rheumatoid Arthritis in Rats.
AB  - OBJECTIVE: Shark type II collagen (SCII) is extracted as a glycoprotein from the
      cartilage of blue shark (Prionace glauca). We aim to confirm the effects of oral
      tolerance of SCII on inflammatory and immune responses to the ankle joint of
      rheumatoid-arthritis rats induced by Complete Freund's Adjuvant (CFA). MATERIALS
      AND METHODS: The onset of rheumatoid arthritis (RA) was observed 14 +/- x days
      after injection of CFA. Rats in the control group were treated with acetic acid
      by oral administration (0.05 mmol kg-1d-1, days 14-28), while rats in
      experimental groups were treated by oral administration with SCII (1 or 3 mg kg
      1d-1, days 14-28), Tripterygium wilfordii polyglycosidium (TWP) (10 mg kg-1d-1,
      days 14-28), and bovine type II collagen from US (US-CII) (1 mg kg-1d-1, days 14
      28), respectively. The severity of arthritis was evaluated by the articular
      swelling. The immunological indexes observed included delayed type
      hypersensitivity (DTH) reaction, the level of interleukins 10 (IL-10) in rat
      blood serum and morphological characterization. Mixed lymphocyte culture (MLC)
      was performed to investigate the relationship between T cell apoptosis and
      specific immune tolerance induced by SCII. RESULTS: Treatment with SCII for 2
      weeks significantly attenuated the acute inflammation. The rats orally
      administrated with SCII at the level of 3 mg kg-1d-1 (SCII 3) and US-CII had
      decreased DTH reaction compared with rats in control group. Rats treated with
      SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of
      10 MUg/L could help to significantly enhance level of Fas/Apo-1 in T cell in
      vitro. The result of histological staining indicated that the recovery of the
      articular membranes of ankle joint in SCII 3 group was greatly enhanced.
      CONCLUSIONS: Our results suggest that appropriate dose of SCII can not only
      ameliorate symptoms but also modify the disease process of Complete-Freunds
      Adjuvant-induced arthritis. Oral administration of SCII might be a potential
      candidate as a novel drug for further investigation.

PMID- 24281406
TI  - On the regulatory approval pathway of biosimilar products.
AB  - Biosimilars (or follow-on biologics) are a new class of medicine which enters the
      market subsequent to a previously approved version. They have demonstrated
      similarity to innovator biologic products in terms of quality, safety, and
      efficacy. The EMA has taken the lead in the regulatory approval framework for
      biosimilar products, and WHO has published guidelines on the evaluation of
      biosimilars in order to facilitate the global harmonization. Based on EMA and WHO
      guidelines, many other countries such as Canada, Japan and Korea have also issued
      their own guidance for evaluating follow-on biologics. The US FDA was authorized
      to approve follow-on biologics by the BPCI Act passed by the US Congress on March
      23, 2010, and has just issued a draft guidance in early 2012. The basic concepts
      and main principles of approving biosimilars are similar among various nations,
      notwithstanding some differences in regard to the scope, the choice of reference
      product, and the data requirement. This article reviews the regulatory approval
      pathway of biosimilar products in different regions. 

PMID- 24281407
TI  - Epigenetic mechanisms and therapeutic perspectives for neurodevelopmental
      disorders.
AB  - The number of children with mild neurodevelopmental disorders, such as autism,
      has been recently increasing in advanced countries. This increase is probably
      caused by environmental factors rather than genetic factors, because it is
      unlikely that genetic mutation rates suddenly increased within a short period.
      Epigenetics is a mechanism that regulates gene expression, depending not on the
      underlying DNA sequence but on the chemical modifications of DNA and histone
      proteins. Because mental stress can alter the epigenetic status in neuronal
      cells, environmental factors may alter brain function through epigenetic changes.
      However, one advantage of epigenetic changes is their reversibility. Therefore,
      diseases due to abnormal epigenetic regulation are theoretically treatable. In
      fact, several drugs for treating mental diseases are known to have restoring
      effects on aberrant epigenetic statuses, and a novel therapeutic strategy
      targeting gene has been developed. In this review, we discuss epigenetic
      mechanisms of congenital and acquired neurodevelopmental disorders, drugs with
      epigenetic effects, novel therapeutic strategies for epigenetic diseases, and
      future perspectives in epigenetic medicine. 

PMID- 24281408
TI  - Stroke prevention in atrial fibrillation: latest clinical trials and guidelines.
AB  - Atrial Fibrillation (AF) is the most common sustained arrhythmia and 1/6 strokes
      is attributed to AF. The cornerstone of treatment remains maintaining sinus
      rhythm or appropriate ventricular rate control in addition to prevention of
      stroke. Oral anticoagulation therapy (OAC) with vitamin K antagonists (VKAs) has
      been the gold standard for almost 50 years and a significant reduction in the
      risk of stroke in patients with AF has been demonstrated. Nonetheless, only 50%
      of patients with guideline recommendations for OAC treatment actually receive
      VKAs and half of these will discontinue therapy within 3 to 5 years with only
      another half achieving therapeutic ranges more than 50% of the time. The
      aforementioned limitations in addition with frequent blood monitoring have
      prompted the development of a series of new OAC therapies. The present review
      focuses on the current pharmacological management for stroke prevention in
      patients with AF based on current and emerging evidence. 

PMID- 24281409
TI  - Ivabradine prevents heart rate acceleration in patients with chronic obstructive
      pulmonary disease and coronary heart disease after salbutamol inhalation.
AB  - Accelerated sinus rhythm is an important side effect of inhaled salbutamol which
      is especially harmful in patients with chronic obstructive pulmonary disease
      (COPD) and coronary heart disease (CHD). Cross-over, randomized, open label study
      design. 20 patients (18 males and two females) with COPD stage II-IV and
      comorbide CHD NYHA class I-III were included. Spirometry with 400 mg salbutamol
      inhalation was performed at two consecutive days of the study. Patients in group
      I were prescribed 5 mg ivabradine per os 3 h before salbutamol inhalation solely
      on the first day of the study and patients of group II received 5 mg ivabradine
      only on the second day of the study. Salbutamol caused a significant increase of
      HR by 5.5 bpm (95% CI 0.8; 10.2, p < 0.03). After ivabradine ingestion salbutamol
      did not change HR significantly by -2.4 bpm (-7.0; 2.3, p = 0.33). The
      attenuation of HR elevation by ivabradine was significant, p < 0.01. Salbutamol
      alone increased FEV1 by 6.0% (2.7; 9.3, p < 0.01). This effect was not impaired
      by ivabradine (FEV1 increase by 7.7% (2.8; 12.6, p < 0.01 versus baseline, p =
      0.5 versus no ivabradine). Ivabradine 5 mg per os prevents heart rate
      acceleration after inhalation of 400 mg salbutamol. Ivabradine has no impact on
      lung function in patients with moderate-to-very-severe COPD and CHD comorbidity. 

PMID- 24281410
TI  - Bactericidal activity of black silicon.
AB  - Black silicon is a synthetic nanomaterial that contains high aspect ratio
      nanoprotrusions on its surface, produced through a simple reactive-ion etching
      technique for use in photovoltaic applications. Surfaces with high aspect-ratio
      nanofeatures are also common in the natural world, for example, the wings of the
      dragonfly Diplacodes bipunctata. Here we show that the nanoprotrusions on the
      surfaces of both black silicon and D. bipunctata wings form hierarchical
      structures through the formation of clusters of adjacent nanoprotrusions. These
      structures generate a mechanical bactericidal effect, independent of chemical
      composition. Both surfaces are highly bactericidal against all tested Gram
      negative and Gram-positive bacteria, and endospores, and exhibit estimated
      average killing rates of up to ~450,000 cells min(-1) cm(-2). This represents the
      first reported physical bactericidal activity of black silicon or indeed for any
      hydrophilic surface. This biomimetic analogue represents an excellent prospect
      for the development of a new generation of mechano-responsive, antibacterial
      nanomaterials.

PMID- 24281411
TI  - The effects of mindfulness-based stress reduction program on the mental health of
      family caregivers: a randomized controlled trial.
AB  - BACKGROUND: Caregivers of people with chronic conditions are more likely than non
      caregivers to have depression and emotional problems. Few studies have examined
      the effectiveness of mindfulness-based stress reduction (MBSR) in improving their
      mental well-being. METHODS: Caregivers of persons with chronic conditions who
      scored 7 or above in the Caregiver Strain Index were randomly assigned to the 8
      week MBSR group (n = 70) or the self-help control group (n = 71). Validated
      instruments were used to assess the changes in depressive and anxiety symptoms,
      quality of life, self-efficacy, self-compassion and mindfulness. Assessments were
      conducted at baseline, post-intervention and at the 3-month follow-up. RESULTS:
      Compared to the participants in the control group, participants in the MBSR group
      had a significantly greater decrease in depressive symptoms at post-intervention
      and at 3 months post-intervention (p < 0.01). The improvement in state anxiety
      symptoms was significantly greater among participants in the MBSR group than
      those of the control group at post-intervention (p = 0.007), although this
      difference was not statistically significant at 3 months post-intervention (p =
      0.084). There was also a statistically significant larger increase in self
      efficacy (controlling negative thoughts; p = 0.041) and mindfulness (p = 0.001)
      among participants in the MBSR group at the 3-month follow-up compared to the
      participants in the control group. No statistically significant group effects
      (MBSR vs. control) were found in perceived stress, quality of life or self
      compassion. CONCLUSIONS: MBSR appears to be a feasible and acceptable
      intervention to improve mental health among family caregivers with significant
      care burden, although further studies that include an active control group are
      needed to make the findings more conclusive.

PMID- 24281412
TI  - Electrofluorochromic detection of cyanide anions using a benzothiadiazole
      containing conjugated copolymer.
AB  - Selective detection of cyanide anions is realized via electrofluorochromism of a
      benzothiadiazole-containing conjugated copolymer because oxidative fluorescence
      quenching induced by positive potentials can be significantly weakened by
      interaction between nucleophilic cyanide and electron-deficient benzothiadiazole.

PMID- 24281414
TI  - miR-200b suppresses cell growth, migration and invasion by targeting Notch1 in
      nasopharyngeal carcinoma.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) are a class of small noncoding RNA molecules
      that play important roles in carcinogenesis and tumor progression. We
      investigated the roles and mechanisms of miR-200b in human nasopharyngeal
      carcinoma (NPC). METHODS: We used quantitative real-time polymerase chain
      reaction (qRT-PCR) analyses to measure levels of miR-200b and Notch1 in NPC
      specimens and cell lines. Human NPC cell lines stably expressing miR-200b or
      control were used to analyze the tumour-suppressive effect of miR-200b.
      Luciferase reporter assays were used to determine the association between miR
      200b and the Notch1 3' untranslated region. RESULTS: We found that miR-200b is
      significantly downregulated in NPC tissues and cell lines. Gain-of-function and
      loss-of-function studies demonstrated that miR-200b suppresses NPC cell growth,
      migration and invasion in vitro. Importantly, overexpression of miR-200b
      effectively repressed tumor growth in nude mouse models. Integrated analysis
      identified Notch1 as a direct and functional target of miR-200b. Overexpression
      of Notch1 reversed the inhibitory effect of miR-200b on NPC cell growth and
      invasion. CONCLUSION: These results indicate that miR-200b exerts tumor
      suppressive effects in NPC carcinogenesis through the suppression of Notch1
      expression and suggest a therapeutic application of miR-200b in NPC.

PMID- 24281413
TI  - Rates of evolution of hominoid seminal proteins are correlated with function and
      expression, rather than mating system.
AB  - In species where females mate with multiple males during a single ovulatory
      cycle, sperm competition is hypothesized to increase the rate of adaptive
      evolution of proteins expressed in male reproductive tissues through recurrent
      selective sweeps (positive selection). The hominoids, comprising apes and humans,
      are a group of closely related primates with extensive variation in mating
      behaviors and predicted levels of sperm competition. Since previous studies of
      individual male reproductive genes have shown evidence of positive selection, we
      estimated rates of evolution of a comprehensive set of proteins expressed in
      ejaculated semen. Our results show that these proteins in hominoids do not have
      elevated rates of nonsynonymous substitutions (Ka) compared with a control
      dataset of nonreproductive genes. Species with greater sperm competition do not
      have faster rates of seminal protein evolution. Although at these broad levels
      our hypotheses were not confirmed, further analyses indicate specific patterns of
      molecular evolution. Namely, the Ka of seminal genes is more strongly correlated
      with measures of tissue specificity than nonreproductive genes, suggesting that
      the former may more readily adapt to tissue-specific functions. Proteins
      expressed from the seminal vesicles evolve more rapidly than those from other
      male reproductive tissues. Also, several gene ontology categories show elevated
      rates of protein evolution, not seen in the control data set. While the
      generalization that male reproductive genes evolve rapidly in hominoids is an
      oversimplification, a subset of proteins can be identified that are likely
      targets for adaptive evolution driven by sexual selection.

PMID- 24281416
TI  - Influence of high-pressure treatment on charge carrier transport in PbS colloidal
      quantum dot solids.
AB  - We investigated the effects of high-pressure treatment on charge carrier
      transport in PbS colloidal quantum dot (CQD) solids. We applied high pressure to
      PbS CQD solids using nitrogen gas to reduce the inter-dot distance. Using this
      simple process, we obtained conductive PbS CQD solids. Terahertz time-domain
      spectroscopy was used to study charge carrier transport as a function of
      pressure. We found that the minimum pressure needed to increase the dielectric
      constant, conductivity, and carrier mobility was 4 MPa. All properties
      dramatically improved at 5 MPa; for example, the mobility increased from 0.13
      cm(2) V(-1) s(-1) at 0.1 MPa to 0.91 cm(2) V(-1) s(-1) at 5 MPa. We propose this
      simple process as a nondestructive approach for making conductive PbS CQD solids
      that are free of chemical and physical defects. 

PMID- 24281415
TI  - Plasticity of the worker bumblebee brain in relation to age and rearing
      environment.
AB  - The environment experienced during development can dramatically affect the brain,
      with possible implications for sensory processing, learning, and memory. Although
      the effects of single sensory modalities on brain development have been
      repeatedly explored, the additive or interactive effects of multiple modalities
      have been less thoroughly investigated. We asked how experience with multisensory
      stimuli affected brain development in the bumblebee Bombus impatiens. First, to
      establish the timeline of brain development during early adulthood, we estimated
      regional brain volumes across a range of ages. We discovered significant age
      related volume changes in nearly every region of the brain. Next, to determine
      whether these changes were dependent upon certain environmental stimuli, we
      manipulated the visual and olfactory stimuli available to newly emerged bumblebee
      workers in a factorial manner. Newly emerged bumblebees were maintained in the
      presence or absence of supplemental visual and/or olfactory stimuli for 7 days,
      after which the volumes of several brain regions were estimated. We found that
      the volumes of the mushroom body lobes and calyces were larger in the absence of
      visual stimuli. Additionally, visual deprivation was associated with the
      expression of larger antennal lobes, the primary olfactory processing regions of
      the brain. In contrast, exposure to plant-derived olfactory stimuli did not have
      a significant effect on brain region volumes. This study is the first to explore
      the separate and interactive effects of visual and olfactory stimuli on bee brain
      development. Assessing the timing and sensitivity of brain development is a first
      step toward understanding how different rearing environments differentially
      affect regional brain volumes in this species. Our findings suggest that
      environmental factors experienced during the first week of adulthood can modify
      bumblebee brain development in many subtle ways.

PMID- 24281417
TI  - EGFR, BRAF and KRAS status in patients undergoing pulmonary metastasectomy from
      primary colorectal carcinoma: a prospective follow-up study.
AB  - BACKGROUND: Pulmonary metastasectomy is an integral part of the interdisciplinary
      treatment of patients with pulmonary metastases (PMs) from colorectal carcinoma
      (CRC). Although alterations in the epidermal growth factor receptor (EGFR)
      pathway are common in CRC, there is still insufficient data regarding PM. We
      hypothesized that EGFR expression and Kirsten rat sarcoma viral oncogene homolog
      (KRAS)/BRAF mutations (Mts) might be associated with clinicopathological
      variables and the outcome in patients undergoing pulmonary metastasectomy.
      METHODS: In this single-center study, 44 patients undergoing pulmonary
      metastasectomy from primary CRC were included and prospectively followed up.
      Tissue specimens of resected PMs were assessed. Restriction fragment length
      analysis was used for BRAF V600E and KRAS codons 12 and 13 Mt analyses. EGFR
      expression was evaluated by immunohistochemistry. Patients were followed up in 3
      6-month intervals. RESULTS: EGFR expression was evident in 49 % of the PMs,
      whereas Mts in KRAS and BRAF were detected in 48 and 0 %, respectively. Time to
      lung-specific recurrence after metastasectomy was significantly decreased in
      patients with KRAS mutated PMs in univariate (p = 0.013) and multivariate
      analysis (p = 0.035), whereas EGFR expression had no impact on recurrence free
      survival. Moreover, KRAS Mts were associated with the number of PMs (p = 0.037)
      and with the lung as first site of recurrence after metastasectomy (p = 0.047).
      DISCUSSION: This is the first evaluation of EGFR pathway alterations in the
      setting of pulmonary metastasectomy. Our data suggest that patients with KRAS Mts
      are at high risk for early pulmonary recurrence and have a more diffuse pattern
      of metastasis. These findings may have impact on the therapeutic management of
      CRC patients with pulmonary spreading.

PMID- 24281419
TI  - A multifactorial histopathologic score for the prediction of prognosis of
      resected esophageal adenocarcinomas after neoadjuvant chemotherapy.
AB  - BACKGROUND: For esophageal adenocarcinoma treated with neoadjuvant chemotherapy,
      postoperative staging classifications initially developed for non-pretreated
      tumors may not accurately predict prognosis. We tested whether a multifactorial
      TNM-based histopathologic prognostic score (PRSC), which additionally applies to
      tumor regression, may improve estimation of prognosis compared with the current
      Union for International Cancer Control/American Joint Committee on Cancer (UICC)
      staging system. PATIENTS AND METHODS: We evaluated esophageal adenocarcinoma
      specimens following cis/oxaliplatin-based therapy from two separate centers
      (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned
      a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3
      = 2 points; <= 50 % residual tumor/tumor bed = 1 point; >50 % residual
      tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of
      these factors (group A: 3; group B: 4-5; group C: 6) and was correlated with
      patients' overall survival (OS). RESULTS: The PRSC groups showed significant
      differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7
      2.8]), which could also be demonstrated in both cohorts separately (center 1 p <
      0.0001; HR 2.48 [95 % CI 1.8-3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1
      2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than
      the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1-1.2]), and
      assessment of two goodness-of-fit criteria (Akaike Information Criterion and
      Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC
      over the UICC staging. CONCLUSION: The proposed PRSC clearly identifies three
      subgroups with different outcomes and may be more helpful for guiding further
      therapeutic decisions than the UICC staging system.

PMID- 24281418
TI  - SRC family kinase inhibition as a novel strategy to augment melphalan-based
      regional chemotherapy of advanced extremity melanoma.
AB  - BACKGROUND: Src kinase inhibition has been shown to augment the efficacy of
      chemotherapy. Dasatinib, a dual Src/Abl kinase inhibitor approved for the
      treatment of CML, is under investigation as monotherapy for tumors with abnormal
      Src signaling, such as melanoma. The goal of this study was to determine if Src
      kinase inhibition using dasatinib could enhance the efficacy of regionally
      administered melphalan in advanced extremity melanoma. METHODS: The mutational
      status of c-kit and patterns of gene expression predictive of dysregulated Src
      kinase signaling were evaluated in a panel of 26 human melanoma cell lines. The
      effectiveness of dasatinib was measured by quantifying protein expression and
      activation of Src kinase, focal adhesion kinase, and Crk-associated substrate
      (p130(CAS)), in conjunction with in vitro cell viability assays using seven
      melanoma cell lines. Utilizing a rat model of regional chemotherapy, we evaluated
      the effectiveness of systemic dasatinib in conjunction with regional melphalan
      against the human melanoma cell line, DM443, grown as a xenograft. RESULTS: Only
      the WM3211 cell line harbored a c-kit mutation. Significant correlation was
      observed between Src-predicted dysregulation by gene expression and sensitivity
      to dasatinib in vitro. Tumor doubling time for DM443 xenografts treated with
      systemic dasatinib in combination with regional melphalan (44.8 days) was
      significantly longer (p = 0.007) than either dasatinib (21.3 days) or melphalan
      alone (24.7 days). CONCLUSIONS: Systemic dasatinib prior to melphalan-based
      regional chemotherapy markedly improves the efficacy of this alkylating agent in
      this melanoma xenograft model. Validation of this concept should be considered in
      the context of a regional therapy clinical trial.

PMID- 24281421
TI  - Joint attention initiation with and without positive affect: risk group
      differences and associations with ASD symptoms.
AB  - Infants at risk for autism spectrum disorders (ASD) may have difficulty
      integrating smiles into initiating joint attention (IJA) bids. A specific IJA
      pattern, anticipatory smiling, may communicate preexisting positive affect when
      an infant smiles at an object and then turns the smile toward the social partner.
      We compared the development of anticipatory smiling at 8, 10, and 12 months in
      infant siblings of children with ASD (high-risk siblings) and without ASD (low
      risk siblings). High-risk siblings produced less anticipatory smiling than low
      risk siblings, suggesting early differences in communicating preexisting positive
      affect. While early anticipatory smiling distinguished the risk groups, IJA not
      accompanied by smiling best predicted later severity of ASD-related behavioral
      characteristics among high-risk siblings. High-risk infants appear to show lower
      levels of motivation to share positive affect with others. However, facility with
      initiating joint attention in the absence of a clear index of positive affective
      motivation appears to be central to the prediction of ASD symptoms. 

PMID- 24281422
TI  - Auditory Stream Segregation in Autism Spectrum Disorder: Benefits and Downsides
      of Superior Perceptual Processes.
AB  - Auditory stream segregation allows us to organize our sound environment, by
      focusing on specific information and ignoring what is unimportant. One previous
      study reported difficulty in stream segregation ability in children with Asperger
      syndrome. In order to investigate this question further, we used an interleaved
      melody recognition task with children in the autism spectrum disorder (ASD). In
      this task, a probe melody is followed by a mixed sequence, made up of a target
      melody interleaved with a distractor melody. These two melodies have either the
      same [0 semitone (ST)] or a different mean frequency (6, 12 or 24 ST separation
      conditions). Children have to identify if the probe melody is present in the
      mixed sequence. Children with ASD performed better than typical children when
      melodies were completely embedded. Conversely, they were impaired in the ST
      separation conditions. Our results confirm the difficulty of children with ASD in
      using a frequency cue to organize auditory perceptual information. However,
      superior performance in the completely embedded condition may result from
      superior perceptual processes in autism. We propose that this atypical pattern of
      results might reflect the expression of a single cognitive feature in autism. 

PMID- 24281423
TI  - Suppression of expression between adjacent genes within heterologous modules in
      yeast.
AB  - Recent studies have shown that proximal arrangement of multiple genes can have
      complex effects on gene expression. For example, in the case of heterologous gene
      expression modules, certain arrangements of the selection marker and the gene
      expression cassette may have unintended consequences that limit the
      predictability and interpretability of module behaviors. The relationship between
      arrangement and expression has not been systematically characterized within
      heterologous modules to date. In this study, we quantitatively measured gene
      expression patterns of the selection marker (KlURA3 driven by the promoter,
      pKlURA) and the gene expression cassette (GFP driven by the galactose-inducible
      GAL1 promoter, pGAL1) in all their possible relative arrangements in
      Saccharomyces cerevisiae. First, we observed that pKlURA activity depends
      strongly on the relative arrangement and the activity of pGAL1. Most notably, we
      observed transcriptional suppression in the case of divergent arrangements:
      pKlURA activity was reduced when pGAL1 was inactive. Based on our nucleosome
      occupancy data, we attribute the observed transcriptional reduction to nucleosome
      repositioning. Second, we observed that pGAL1 activity also depends on the
      relative arrangement of pKlURA. In particular, strains with divergent promoters
      showed significantly different pGAL1 activation patterns from other strains, but
      only when their growth was compromised by lack of uracil. We reasoned that this
      difference in pGAL1 activation patterns arises from arrangement-dependent pKlURA
      activity that can affect the overall cell physiology (i.e., cell growth and
      survival in the uracil-depleted condition). Our results underscore the necessity
      to consider ramifications of promoter arrangement when using synthetic gene
      expression modules. 

PMID- 24281424
TI  - Diversity, differentiation, and linkage disequilibrium: prospects for association
      mapping in the malaria vector Anopheles arabiensis.
AB  - Association mapping is a widely applied method for elucidating the genetic basis
      of phenotypic traits. However, factors such as linkage disequilibrium and levels
      of genetic diversity influence the power and resolution of this approach.
      Moreover, the presence of population subdivision among samples can result in
      spurious associations if not accounted for. As such, it is useful to have a
      detailed understanding of these factors before conducting association mapping
      experiments. Here we conducted whole-genome sequencing on 24 specimens of the
      malaria mosquito vector, Anopheles arabiensis, to further understanding of
      patterns of genetic diversity, population subdivision and linkage disequilibrium
      in this species. We found high levels of genetic diversity within the An.
      arabiensis genome, with ~800,000 high-confidence, single- nucleotide
      polymorphisms detected. However, levels of nucleotide diversity varied
      significantly both within and between chromosomes. We observed lower diversity on
      the X chromosome, within some inversions, and near centromeres. Population
      structure was absent at the local scale (Kilombero Valley, Tanzania) but detected
      between distant populations (Cameroon vs. Tanzania) where differentiation was
      largely restricted to certain autosomal chromosomal inversions such as 2Rb.
      Overall, linkage disequilibrium within An. arabiensis decayed very rapidly
      (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium
      was observed within some inversions, suggesting that recombination is reduced in
      those regions. The overall low levels of linkage disequilibrium suggests that
      association studies in this taxon will be very challenging for all but variants
      of large effect, and will require large sample sizes. 

PMID- 24281425
TI  - Generation of a useful roX1 allele by targeted gene conversion.
AB  - Methods for altering the sequence of endogenous Drosophila melanogaster genes
      remain labor-intensive. We have tested a relatively simple strategy that enables
      the introduction of engineered mutations in the vicinity of existing P-elements.
      This method was used to generate useful alleles of the roX1 gene, which produces
      a noncoding RNA involved in dosage compensation. The desired change was first
      introduced into a genomic clone of roX1 and transgenic flies were generated that
      carry this sequence in a P-element. Targeted transposition was then used to move
      the P-element into roX1. Remobilization of the targeted insertion produced large
      numbers of offspring carrying chromosomes that had precisely introduced the
      engineered sequences into roX1. We postulate that this occurred by gap repair,
      using the P-element on the sister chromatid as template. This strategy was used
      to introduce six MS2 loops into the roX1 gene (roX1(MS2-6)), enabling detection
      of roX1 RNA by a MCP-GFP fusion protein in embryos. The roX1(MS2-6) remains under
      the control of the authentic promoter and within the correct genomic context,
      features expected to contribute to normal roX1 function. The ability to replace
      relatively large blocks of sequence suggests that this method will be of general
      use. 

PMID- 24281426
TI  - Opposing activities of DRM and MES-4 tune gene expression and X-chromosome
      repression in Caenorhabditis elegans germ cells.
AB  - During animal development, gene transcription is tuned to tissue-appropriate
      levels. Here we uncover antagonistic regulation of transcript levels in the
      germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase
      MES-4 (Maternal Effect Sterile-4) marks genes expressed in the germline with
      methylated lysine on histone H3 (H3K36me) and promotes their transcription; MES-4
      also represses genes normally expressed in somatic cells and genes on the X
      chromosome. The DRM transcription factor complex, named for its Dp/E2F,
      Retinoblastoma-like, and MuvB subunits, affects germline gene expression and
      prevents excessive repression of X-chromosome genes. Using genome-scale analyses
      of germline tissue, we show that common germline-expressed genes are activated by
      MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline
      expressed genes. Reciprocally, MES-4 represses and DRM activates a set of
      autosomal soma-expressed genes and overall X-chromosome gene expression.
      Mutations in mes-4 and the DRM subunit lin-54 oppositely skew the transcript
      levels of their common targets and cause sterility. A double mutant restores
      target gene transcript levels closer to wild type, and the concomitant loss of
      lin-54 suppresses the severe germline proliferation defect observed in mes-4
      single mutants. Together, "yin-yang" regulation by MES-4 and DRM ensures
      transcript levels appropriate for germ-cell function, elicits robust but not
      excessive dampening of X-chromosome-wide transcription, and may poise genes for
      future expression changes. Our study reveals that conserved transcriptional
      regulators implicated in development and cancer counteract each other to fine
      tune transcript dosage. 

PMID- 24281429
TI  - De novo rectovaginal fistulation and multisite ulceration as a consequence of
      nicorandil therapy.

PMID- 24281428
TI  - The pattern and distribution of deleterious mutations in maize.
AB  - Most nonsynonymous mutations are thought to be deleterious because of their
      effect on protein sequence and are expected to be removed or kept at low
      frequency by the action of natural selection. Nonetheless, the effect of positive
      selection on linked sites or drift in small or inbred populations may also impact
      the evolution of deleterious alleles. Despite their potential to affect complex
      trait phenotypes, deleterious alleles are difficult to study precisely because
      they are often at low frequency. Here, we made use of genome-wide genotyping data
      to characterize deleterious variants in a large panel of maize inbred lines. We
      show that, despite small effective population sizes and inbreeding, most
      putatively deleterious SNPs are indeed at low frequencies within individual
      genetic groups. We find that genes associated with a number of complex traits are
      enriched for deleterious variants. Together, these data are consistent with the
      dominance model of heterosis, in which complementation of numerous low-frequency,
      weak deleterious variants contribute to hybrid vigor. 

PMID- 24281430
TI  - Morphology of seahorse head hydrodynamically aids in capture of evasive prey.
AB  - Syngnathid fish (seahorses, pipefish and sea dragons) are slow swimmers yet
      capture evasive prey (copepods) using a technique known as the 'pivot' feeding,
      which involves rapid movement to overcome prey escape capabilities. However, this
      feeding mode functions only at short range and requires approaching very closely
      to hydrodynamically sensitive prey without triggering an escape. Here we
      investigate the role of head morphology on prey capture using holographic and
      particle image velocimetry (PIV). We show that head morphology functions to
      create a reduced fluid deformation zone, minimizing hydrodynamic disturbance
      where feeding strikes occur (above the end of the snout), and permits syngnathid
      fish to approach highly sensitive copepod prey (Acartia tonsa) undetected. The
      results explain how these animals can successfully employ short range 'pivot'
      feeding effectively on evasive prey. The need to approach prey with stealth may
      have selected for a head shape that produces lower deformation rates than other
      fish. 

PMID- 24281427
TI  - Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic
      interactors in Caenorhabditis elegans.
AB  - mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for
      nuclear envelope function and chromosome segregation in Caenorhabditis elegans.
      Because mel-28 is a strict maternal-effect lethal gene, its function is required
      in the early embryo but appears to be dispensable for larval development. We
      wanted to test the idea that mel-28 has postembryonic roles that are buffered by
      the contributions of other genes. To find genes that act coordinately with mel
      28, we did an RNA interference-based genetic interaction screen using mel-28 and
      wild-type larvae. We screened 18,364 clones and identified 65 genes that cause
      sterility in mel-28 but not wild-type worms. Some of these genes encode
      components of the nuclear pore. In addition we identified genes involved in
      dynein and dynactin function, vesicle transport, and cell-matrix attachments. By
      screening mel-28 larvae we have bypassed the requirement for mel-28 in the
      embryo, uncovering pleiotropic functions for mel-28 later in development that are
      normally provided by other genes. This work contributes toward revealing the gene
      networks that underlie cellular processes and reveals roles for a maternal-effect
      lethal gene later in development. 

PMID- 24281431
TI  - Minimally invasive surgery for esophageal cancer: a review on sentinel node
      concept.
AB  - BACKGROUND: Lymphoadenectomy is a cornerstone of esophageal cancer treatment, and
      sentinel node (SN) biopsy (SNB) might provide surgeons with an extra tool to
      limit unnecessarily extended lymphadenectomy and to implement a minimally
      invasive approach. The aim of our study was to review all the available
      literature on the use of SNB in esophageal surgery for malignancy. METHODS: The
      review was conducted according to the PRISMA guidelines. A systematic search was
      performed in PubMed, EMBASE, and the Cochrane database to identify all original
      articles on the role of SNB in esophageal cancer. Data on methodologies, tumor
      stage and localization, and results were summarized and used to address relevant
      clinical questions related to the application of the SNB technique in esophageal
      cancer. RESULTS: Twelve studies were included, with a total of 492 patients.
      Different methods for SN identification were used (radionuclide, blue dye,
      computed tomography [CT] lymphography). The pooled values estimated using the
      random-effects model were, respectively: technetium-99 m overall detection rate
      (DR) 0.970 (95 % CI 0.814-0.996), accuracy (ACC) 0.902 (95 % CI 0.736-0.968);
      blue-dye DR 0.971 (95 % CI 0.890-0.993), ACC 0.790 (95 % CI 0.681-0.870); and CT
      lymphoscintigraphy DR 0.970 (95 % CI 0.814-0.996), ACC 0.902 (95 % CI 0.736
      0.968). CONCLUSION: Based on these results, the concept of SN in esophageal
      cancer is technically feasible with an acceptable DR and ACC, and it might be
      applicable in the event of early-stage adenocarcinoma of the gastroesophageal
      junction in patients with a high surgical risk or in a patient where an
      endoscopic resection is taken into consideration. Further studies focused on a
      single tumor type and localizations are needed in order to predict the correct
      utilization of this concept in minimally invasive treatment of esophageal cancer.

PMID- 24281432
TI  - Identifying causes for high readmission rates after stoma reversal.
AB  - BACKGROUND: Unplanned readmissions after colorectal surgery impact patient and
      financial outcomes. Our goal was to identify factors related to readmission in
      ostomy reversal patients. METHODS: Review of a prospective department database
      was performed from 2006 to 2012 to identify patients who underwent an ostomy
      reversal. Patients were stratified into nonreadmitted and readmitted within 30
      days of ostomy reversal. The main outcome measures were predictors of readmission
      and characteristics of patients readmitted and not readmitted. RESULTS: A total
      of 351 ostomy reversals (86 % ileostomy and 14 % colostomy) were analyzed; 44
      patients were readmitted (12.5 %). Readmitted and nonreadmitted patients were
      similar in age, body mass index, gender, comorbidities, indications for the index
      operation, and time to ostomy reversal. Readmitted patients had longer operative
      times (p = 0.002) and length of stay (p = 0.001), more intraoperative blood loss
      (p = 0.003), intraoperative complications (p = 0.005), ICU requirements (p <
      0.0001), need for temporary nursing at discharge (p < 0.001), and higher total
      hospital costs than nonreadmitted patients (p = 0.0162). Longer operative time
      [odds ratio (OR) 1.006, 95 % confidence interval (CI) 1.001-1.012],
      intraoperative complications (OR 7.334, 95 % CI 1.23-43.761), ICU stay (OR 1.291,
      95 % CI 1.18-1.893), delayed discharge (OR 1.085, 95 % CI 1.003-1.173), and
      discharge to skilled nursing facility (OR 6.936, 95 % CI 1.531-31.332) were
      independent predictors of readmission. Ostomy type had no independent effect on
      readmission. CONCLUSIONS: Differences in perioperative and outcomes variables
      exist between readmitted and nonreadmitted patients after ostomy reversal. Longer
      operative times, intraoperative complications, intensive care unit care, longer
      length of stay, and skilled nursing at discharge were independently predictive of
      readmission. These findings can be used to identify high-risk patients
      prospectively, potentially improving clinical outcomes and healthcare
      utilization.

PMID- 24281433
TI  - Condition of muscularis mucosae is a risk factor for lymph node metastasis in T1
      colorectal carcinoma.
AB  - BACKGROUND: The Japanese Society for Cancer of the Colon and Rectum Guidelines
      for the Treatment of Colorectal Cancer 2010 state that curable T1 colorectal
      carcinoma (CRC) after endoscopic resection shows favorable histologic grade,
      absence of vessel involvement, submucosal invasion depth of <1,000 MUm, and low
      grade tumor budding. METHODS: We evaluated 322 consecutive T1 CRCs with LN
      dissection between January 1993 and March 2012. According to the muscularis
      mucosae condition, CRCs were classified into three groups: type A, clearly
      identified; type B, incompletely disrupted with deformity; or type C, completely
      disrupted. We examined the relationship between the muscularis mucosae condition,
      clinicopathological findings, and lymph node (LN) metastasis. RESULTS: The
      overall incidence of LN metastasis was 11.8 % (38/322): 0 % (0/46) for the type A
      group, 7.2 % (7/97) for the type B group, and 17.3 % (31/179) for the type C
      group. In univariate analysis of type B and C groups, unfavorable histologic
      grade, submucosal invasion of >=1,000 MUm, positive lymphatic invasion, high
      grade tumor budding, and the type C group were associated with a significantly
      higher incidence of LN metastasis. In multivariate analysis, high-grade tumor
      budding (P < 0.001, odds ratio [OR] = 4.86), unfavorable histologic grade (P =
      0.026, OR = 4.83), positive lymphatic invasion (P < 0.001, OR = 4.17), and the
      type C group (P = 0.012, OR = 3.38) were significantly associated with LN
      metastasis. The type C group showed a high incidence of moderate/severe lymphatic
      invasion. CONCLUSIONS: The condition of the muscularis mucosae was an indicator
      of LN metastasis in T1 CRC.

PMID- 24281434
TI  - Reply to: long-term cosmetic results after minimally invasive video-assisted
      thyroidectomy.

PMID- 24281435
TI  - Continuous infusion of ibuprofen for treatment of patent ductus arteriosus in
      very low birth weight infants.
AB  - BACKGROUND: Ibuprofen (IBU) has proved as effective as indomethacin in the
      pharmacological closure of hemodynamically significant patent ductus arteriosus
      (HsPDA), with an efficacy inversely related to gestational age (57-89%).
      OBJECTIVE: This study aimed to establish whether continuous infusions of IBU
      could be more effective in very low birth weight infants with no additional
      adverse effects and reduce the need for surgical ligation. METHODS: A
      prospective, randomized, double-dummy study was conducted on 112 very low birth
      weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD
      330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent
      boluses, while the other 56 were administered IBU as a 24-hour continuous
      infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was
      performed before and after treatment, and adverse effects were monitored.
      RESULTS: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36
      of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after
      continuous infusion (p = 0.020), and in 9 of 26 (34.6%) and 24 of 30 (80.0%),
      respectively, in the infants with a gestational age of 23-27 weeks (p = 0.006).
      Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after
      bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical
      ligation was used less after continuous infusion than after bolus IBU (5.5 vs.
      19.6%; p = 0.024). The continuous infusion group had fewer symptoms of
      necrotizing enterocolitis (NEC), especially in the more preterm infants, while
      other neonatal morbidity and mortality rates were similar. CONCLUSION: Continuous
      IBU infusion is more effective than standard boluses for sustained closure of
      HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low
      birth weight infants.

PMID- 24281436
TI  - Adolf Beck (1863-1942) - a pioneer of electroencephalography.

PMID- 24281437
TI  - gamma-Al2O3 nanoparticles synthesised by pulsed laser ablation in liquids: a
      plasma analysis.
AB  - Pulsed laser ablation has proved its reliability for the synthesis of nano
      particles and nano-structured materials, including metastable phases and complex
      stoichiometries. The possible nucleation of the nanoparticles in the gas phase
      and their growth has been little investigated, due to the difficulty of following
      the gas composition as well as the thermodynamic parameters. We show that such
      information can be obtained from the optically active plasma during its short
      lifetime, only a few microseconds for each laser pulse, as a result of a quick
      quenching due to the liquid environment. For this purpose, we follow the laser
      ablation of an alpha-Al2O3 target (corindon) in water, which leads to the
      synthesis of nanoparticles of gamma-Al2O3. The AlO blue-green emission and the
      Al(I) (2)P(0)-(2)S doublet emission provide the electron density, the density
      ratio between the Al atoms and AlO molecules, and the rotational and vibrational
      temperatures of the AlO molecules. These diagnostic considerations are discussed
      in the framework of theoretical studies from the literature (density functional
      theory). We have found that starting from a hot atomized gas, the nucleation
      cannot occur in the first microseconds. We also raise the question of the
      influence of water on the control of the stoichiometry.

PMID- 24281440
TI  - A Quebec village street, winter: Clarence Alphonse Gagnon.

PMID- 24281441
TI  - Excessive antibiotic prescribing for sore throat and acute bronchitis remains
      common.

PMID- 24281442
TI  - FDA questions effectiveness of measures to reduce or prevent illness from eating
      imported spices.

PMID- 24281443
TI  - Do flawed data on caloric intake from NHANES present problems for researchers and
      policy makers?

PMID- 24281444
TI  - More evidence emerges that bats may have spread SARS.

PMID- 24281458
TI  - A piece of my mind. EBM's six dangerous words.

PMID- 24281459
TI  - Oral fluoroquinolone use and retinal detachment: reconciling conflicting findings
      in observational research.

PMID- 24281461
TI  - Effect of thalidomide on clinical remission in children and adolescents with
      refractory Crohn disease: a randomized clinical trial.
AB  - IMPORTANCE: Pediatric-onset Crohn disease is more aggressive than adult-onset
      disease, has high rates of resistance to existing drugs, and can lead to
      permanent impairments. Few trials have evaluated new drugs for refractory Crohn
      disease in children. OBJECTIVE: To determine whether thalidomide is effective in
      inducing remission in refractory pediatric Crohn disease. DESIGN, SETTING, AND
      PATIENTS: Multicenter, double-blind, placebo-controlled, randomized clinical
      trial of 56 children with active Crohn disease despite immunosuppressive
      treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care
      centers in Italy. INTERVENTIONS: Thalidomide, 1.5 to 2.5 mg/kg per day, or
      placebo once daily for 8 weeks. In an open-label extension, nonresponders to
      placebo received thalidomide for an additional 8 weeks. All responders continued
      to receive thalidomide for an additional minimum 52 weeks. MAIN OUTCOMES AND
      MEASURES: Primary outcomes were clinical remission at week 8, measured by
      Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by
      >=25% or >=75% at weeks 4 and 8. Primary outcomes during the open-label follow-up
      were clinical remission and 75% response. RESULTS: Twenty-eight children were
      randomized to thalidomide and 26 to placebo. Clinical remission was achieved by
      significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26
      [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat
      [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement
      was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs
      3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response,
      18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01).
      Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%)
      subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45;
      P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved
      clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of
      clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53
      217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001).
      Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks,
      with peripheral neuropathy the most frequent severe adverse event. CONCLUSIONS
      AND RELEVANCE: In children and adolescents with refractory Crohn disease,
      thalidomide compared with placebo resulted in improved clinical remission at 8
      weeks of treatment and longer-term maintenance of remission in an open-label
      follow-up. These findings require replication to definitively determine clinical
      utility of this treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00720538.

PMID- 24281460
TI  - Effect of micronutrient supplementation on disease progression in asymptomatic,
      antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical
      trial.
AB  - IMPORTANCE: Micronutrient deficiencies occur early in human immunodeficiency
      virus (HIV) infection, and supplementation with micronutrients may be beneficial;
      however, its effectiveness has not been investigated early in HIV disease among
      adults who are antiretroviral therapy (ART) naive. OBJECTIVE: To investigate
      whether long-term micronutrient supplementation is effective and safe in delaying
      disease progression when implemented early in adults infected with HIV subtype C
      who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial
      of supplementation with either daily multivitamins (B vitamins and vitamins C and
      E), selenium alone, or multivitamins with selenium vs placebo in a factorial
      design for 24 months. The study was conducted in 878 patients infected with HIV
      subtype C with a CD4 cell count greater than 350/MUL who were not receiving ART
      at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July
      2009. INTERVENTIONS: Daily oral supplements of B vitamins and vitamins C and E,
      selenium alone, or multivitamins plus selenium, compared with placebo. MAIN
      OUTCOMES AND MEASURES: Reaching a CD4 cell count less than 200/MUL until May
      2008; after this date, reaching a CD4 cell count of 250/MUL or less, consistent
      with the standard of care in Botswana for initiation of ART at the time of the
      study. RESULTS: There were 878 participants enrolled and randomized into the
      study. All participants were ART-naive throughout the study. In intent-to-treat
      analysis, participants receiving the combined supplement of multivitamins plus
      selenium had a significantly lower risk vs placebo of reaching CD4 cell count
      250/MUL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01;
      absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17
      events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events).
      Multivitamins plus selenium in a single supplement, vs placebo, also reduced the
      risk of secondary events of combined outcomes for disease progression (CD4 cell
      count <=250/MUL, AIDS-defining conditions, or AIDS-related death, whichever
      occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100
      person-years; censoring rate, 0.90; 23 events]). There was no effect of
      supplementation on HIV viral load. Multivitamins alone and selenium
      supplementation alone were not statistically different from placebo for any end
      point. Reported adverse events were adjudicated as unlikely to be related to the
      intervention, and there were no notable differences in incidence of HIV-related
      and health-related events among study groups. CONCLUSIONS AND RELEVANCE: In ART
      naive HIV-infected adults, 24-month supplementation with a single supplement
      containing multivitamins and selenium was safe and significantly reduced the risk
      of immune decline and morbidity. Micronutrient supplementation may be effective
      when started in the early stages of HIV disease.

PMID- 24281462
TI  - Association between oral fluoroquinolone use and retinal detachment.
AB  - IMPORTANCE: A recent study of ophthalmologic patients found a strong association
      between fluoroquinolone use and retinal detachment. Given the prevalent use of
      fluoroquinolones, this could, if confirmed in the general population, translate
      to many excess cases of retinal detachment that are potentially preventable.
      OBJECTIVE: To investigate if oral fluoroquinolone use is associated with an
      increased risk of retinal detachment. DESIGN, SETTING, AND PARTICIPANTS: A
      nationwide, register-based cohort study in Denmark from 1997 through 2011, using
      linked data on participant characteristics, filled prescriptions, and cases of
      retinal detachment with surgical treatment (scleral buckling, vitrectomy, or
      pneumatic retinopexy). The cohort included 748,792 episodes of fluoroquinolone
      use (660,572 [88%] ciprofloxacin) and 5,520,446 control episodes of nonuse. MAIN
      OUTCOMES AND MEASURES: Poisson regression was used to estimate rate ratios (RRs)
      for incident retinal detachment, adjusting for a propensity score that included a
      total of 21 variables. The risk windows were classified as current use (days 1-10
      from start of treatment), recent use (days 11-30), past use (days 31-60), and
      distant use (days 61-180). RESULTS: A total of 566 cases of retinal detachment
      occurred, of which 465 (82%) were rhegmatogenous detachments; 72 in
      fluoroquinolone users and 494 in control nonusers. The crude incidence rate was
      25.3 cases per 100,000 person-years in current users, 18.9 in recent users, 26.8
      in past users, and 24.8 in distant users compared with 19.0 in nonusers. Compared
      with nonuse, fluoroquinolone use was not associated with a significantly
      increased risk of retinal detachment: the adjusted RRs were 1.29 (95% CI, 0.53 to
      3.13) for current use; 0.97 (95% CI, 0.46 to 2.05) for recent use; 1.37 (95% CI,
      0.80 to 2.35) for past use; and 1.27 (95% CI, 0.93 to 1.75) for distant use. The
      absolute risk difference, estimated as the adjusted number of retinal detachment
      cases per 1,000,000 treatment episodes, was 1.5 (95% CI, -2.4 to 11.1) for
      current use. CONCLUSIONS AND RELEVANCE: In this cohort study based on the general
      Danish population, oral fluoroquinolone use was not associated with increased
      risk of retinal detachment. Given its limited power, this study can only rule out
      more than a 3-fold increase in the relative risk associated with current
      fluoroquinolone use; however, any differences in absolute risk are likely to be
      of minor, if any, clinical significance.

PMID- 24281463
TI  - Jaw lesion and discomfort.

PMID- 24281464
TI  - Detection of undiagnosed HIV among state prison entrants.

PMID- 24281465
TI  - Health care cost control and views of physicians.

PMID- 24281466
TI  - Health care cost control and views of physicians.

PMID- 24281467
TI  - Health care cost control and views of physicians--reply.

PMID- 24281468
TI  - Pitfalls of population-based preventive medicine.

PMID- 24281469
TI  - Health care cost control and views of physicians--reply.

PMID- 24281470
TI  - Sharing of Medicare claims data.

PMID- 24281471
TI  - Pitfalls of population-based preventive medicine--reply.

PMID- 24281472
TI  - Sharing of Medicare claims data--reply.

PMID- 24281474
TI  - The reinspiration of expired air.

PMID- 24281475
TI  - JAMA patient page. Antibiotic resistance.

PMID- 24281476
TI  - Focusing and imaging with increased numerical apertures through multimode fibers
      with micro-fabricated optics.
AB  - The use of individual multimode optical fibers in endoscopy applications has the
      potential to provide highly miniaturized and noninvasive probes for microscopy
      and optical micromanipulation. A few different strategies have been proposed
      recently, but they all suffer from intrinsically low resolution related to the
      low numerical aperture of multimode fibers. Here, we show that two-photon
      polymerization allows for direct fabrication of micro-optics components on the
      fiber end, resulting in an increase of the numerical aperture to a value that is
      close to 1. Coupling light into the fiber through a spatial light modulator, we
      were able to optically scan a submicrometer spot (300 nm FWHM) over an extended
      region, facing the opposite fiber end. Fluorescence imaging with improved
      resolution is also demonstrated.

PMID- 24281477
TI  - Shape control of elemental distributions inside a glass by simultaneous
      femtosecond laser irradiation at multiple spots.
AB  - The spatial distributions of elements in a glass can be modulated by irradiation
      with high repetition rate femtosecond laser pulses. However, the shape of the
      distribution is restricted to being axially symmetric about the laser beam axis
      due to the isotropic diffusion of photo-thermal energy. In this study, we
      describe a method to control the shape of the elemental distribution more
      flexibly by simultaneous irradiation at multiple spots using a spatial light
      modulator. The accumulation of thermal energy was induced by focusing 250 kHz fs
      laser pulses at a single spot inside an alumino-borosilicate glass, and the
      transient temperature distribution was modulated by focusing 1 kHz laser pulses
      at four spots in the same glass. The resulting modification was square-shaped. A
      simulation of the mean diffusion length of molten glass demonstrated that the
      transient diffusion of elements under heat accumulation and repeated temperature
      elevation at multiple spots caused the square shape of the distribution.

PMID- 24281478
TI  - High-efficiency light-trapping effect using silver nanoparticles on thin
      amorphous silicon subwavelength structure.
AB  - In this Letter, we experimentally demonstrate a hybrid structure consisting of
      metal nanoparticles deposited onto a subwavelength structure (SWS), which further
      increases the absorption of thin amorphous silicon (a-Si) and can possibly lead
      to a reduction in the minimum required thickness of the a-Si layer. Experimental
      results show that backscattering of the silver nanoparticles (Ag NPs) deposited
      on the top surface can be suppressed dramatically (by 85.5%) by the Ag NPs
      deposited on the SWS. We also experimentally prove that the thin a-Si SWS only
      lowers the surface reflectivity and does not increase the absorption rate of the
      material. The absorption of the thin a-Si layer can be increased by depositing Ag
      NPs onto a thin a-Si SWS, which not only reduces the backscattering of the metal
      NPs but also increases the light-trapping effect within thin a-Si through
      localized surface plasmon resonance properties. This decrease of reflection and
      increase in the light-trapping effect of Ag NPs on cone-shaped thin a-Si SWSs
      leads to extremely high average absorption (86.14%) within a 400 nm thick a-Si
      layer.

PMID- 24281479
TI  - Microwave photonics for space-time compression of ultrabroadband signals through
      multipath wireless channels.
AB  - We employed photonic radio frequency (RF) arbitrary waveform generation to
      demonstrate space-time compression of ultrabroadband wireless signals through
      highly scattering multipath channels. To the best of our knowledge, this is the
      first experimental report that explores an RF-photonic transmitter to both
      characterize channel dispersions in real wireless environments and generate
      predistorted waveforms to achieve focusing through the multipath channels. Our
      experiments span a three octave frequency range of 2-18 GHz, nearly an order of
      magnitude beyond the ~2 GHz instantaneous bandwidth reported in previous
      spatiotemporal focusing experiments relying on electronic waveform generators.

PMID- 24281480
TI  - Transformations induced in bulk amorphous silica by ultrafast laser direct
      writing.
AB  - A transmission electron microscopy study of nanogratings formed in bulk amorphous
      silica by direct writing with an ultrafast pulsed laser with a radiation
      wavelength of 1030 nm and pulse duration of 560 fs is presented. The results
      achieved show that the nanogratings are composed of planar nanostructures with an
      average periodicity of 250 nm and typical thickness of about 30 nm, consisting of
      alternating layers of heavily damaged material and layers of material where a
      dense precipitation of nanocrystals occurred. The crystallization of silica to
      form these nanocrystals can be explained by the large pressures and temperatures
      reached in these regions as a result of nanoplasma formation and recombination.

PMID- 24281481
TI  - All-fiber processing of terahertz-bandwidth signals based on cascaded tapered
      fibers.
AB  - Tapered single-mode fibers are employed to perform dynamic pulse shaping in a
      bandwidth of several terahertz. The transfer function of cascaded biconical
      tapers is controlled by introducing a phase shift into one of them through
      mechanical stretching. It is a simple and low-cost technique with potential to
      process signals with bandwidths as large as those allocated by standard optical
      fiber while introducing little degradation. Femtosecond pulses are shaped to
      prove the concept. 

PMID- 24281482
TI  - Measurement of higher-order mode propagation losses in effectively single mode
      fibers.
AB  - We present a direct and nondestructive measurement of the propagation loss of
      higher-order modes (HOMs) in effectively single-mode fibers. Lossy HOMs are
      excited by applying local stress at various points alongside a straight single
      mode fiber. The change of the HOM power as a function of the propagation distance
      is recorded at the fiber end by performing a modal decomposition with a
      correlation filter. The results for the HOM propagation loss are compared to
      simulations yielding very good agreement. 

PMID- 24281483
TI  - Increased detection sensitivity of surface plasmon sensors using oblique induced
      resonant coupling.
AB  - Increased detection sensitivity was achieved by adjusting the incident angle on
      periodic gold nanostructures that induced a resonant coupling between surface and
      substrate surface plasmon modes. For 500 nm-period gold nanoslits, a small
      incident angle, 7 degrees , resulted in 2.64 times narrower linewidth and a 1.8
      times increase in the figure of merit as compared to normal incidence.
      Furthermore, the intensity sensitivity was increased 4.5 times due to the change
      in the resonant coupling and redshift of the surface plasmon mode.

PMID- 24281484
TI  - Raman lasing in As2S3 high-Q whispering gallery mode resonators.
AB  - We report the first observation of a nonlinear process in a chalcogenide
      microresonator. Raman scattering and stimulated Raman scattering leading to laser
      oscillation is observed in microspheres made of As2S3. The coupled pump power
      threshold is as low as 13 MUW using a pump wavelength of 1550 nm. The quality
      factor of the chalcogenide microresonator is also the highest ever reported with
      Q>7*10(7).

PMID- 24281485
TI  - Coherent perfect absorption and reflection in slow-light waveguides.
AB  - We identify a family of unusual slow-light modes occurring in lossy multimode
      grating waveguides, for which either the forward or backward mode components, or
      both, are degenerate. In the fully degenerate case, the response can be modulated
      between coherent perfect absorption (zero reflection) and perfect reflection by
      varying the wave amplitudes in a uniform input waveguide. The perfectly absorbed
      wave has anomalously short absorption length, scaling as the inverse one-third
      power of the absorptivity. 

PMID- 24281486
TI  - Far-field mapping of the longitudinal magnetic and electric optical fields.
AB  - In this Letter, we demonstrate the experimental mapping of the longitudinal
      magnetic and electric optical fields with a standard scanning microscope that
      involves a high-numerical-aperture far-field objective. The imaging concept
      relies upon the insertion of an azimuthal or a radial polarizer within the
      detection path of the microscope that acts as an optical electromagnetic filter
      aimed at transmitting selectively to the detector the signal from the magnetic or
      electric longitudinal fields present in the detection volume, respectively. The
      resulting system is thus versatile, noninvasive, and of high resolution, and
      shows high detection efficiencies. Magnetic optical properties of physical and
      biological micro- and nano-structures may thus be revealed with a far-field
      microscope. 

PMID- 24281487
TI  - Refractive-index sensitivities of hybrid surface-plasmon resonances for a core
      shell circular silver nanotube sensor.
AB  - We study the scattering and absorption of an H-polarized plane electromagnetic
      wave by a circular silver nanotube in the visible range of wavelengths using the
      separation of variables. The computed spectra of the extinction cross section
      display several hybrid localized surface-plasmon resonances of the dipole and
      multipole type. Analytical equations are derived for their resonance wavelengths.
      Bulk refractive-index sensitivities of nanotube-based sensors are determined,
      showing higher values for multipole resonances. 

PMID- 24281488
TI  - Bit rate adaptable operation of a hybrid integrated wavelength converter using a
      semiconductor optical amplifier type Mach-Zehnder interferometer.
AB  - A bit rate adaptable all-optical wavelength conversion operation of a
      semiconductor optical amplifier Mach-Zehnder interferometer (SOA-MZI) with a
      selectable push-pull-delay configuration, consisting of silica-based MZI-type
      variable power splitters and cascaded delay switches, was achieved. It consists
      of two SOAs, one variable power splitter, four MZI-type switches, and three delay
      lines on one chip. Eight-level delay times, from 0 to 35 ps, incremented in steps
      of 5 ps, can be selected by controlling the voltages applied to the thermo-optic
      switches. The wavelength conversion operation at a bit rate of 25 and 40 Gbps
      with push-pull delay of 20 and 15 ps was achieved.

PMID- 24281489
TI  - Upconversion detection near 2 MUm at the single photon level.
AB  - We have demonstrated upconversion detection at the single photon level in the 2
      MUm spectral window using a pump wavelength near 1550 nm, a periodically poled
      lithium niobate (PPLN) waveguide, and a volume Bragg grating (VBG) to reduce
      noise. We achieve a system photon detection efficiency of 10%, with a noise count
      rate of 24,500 counts per second, competitive with other 2 MUm single photon
      detection technologies. This detector has potential applications in environmental
      gas monitoring, life science, and classical and quantum communication.

PMID- 24281490
TI  - Ultra-flexible multiband terahertz metamaterial absorber for conformal geometry
      applications.
AB  - Standard optical lithography relying on clean room and microelectronic facilities
      is used to fabricate a thin-flexible metamaterial absorber, designed to operate
      at submillimeter wavelengths over the 0.1-1 THz frequency band. Large terahertz
      absorption has been demonstrated numerically and through experimental
      measurements with a maximum level of about 80%. We put emphasis in this present
      work on the use of single-sized "meta-cells" to achieve multiple absorption
      peaks. Furthermore, the use of a thin-flexible dielectric spacer makes it
      promising for stealth technology applications in order to disguise objects and
      make them less visible to radar and other detection methods.

PMID- 24281492
TI  - Engineering-reflected phase in Fabry-Perot sensors with resonant mirrors.
AB  - Fabry-Perot cavities made with photonic crystal (PC) mirrors and other resonant
      structures exhibit nontraditional characteristics due to the strong wavelength
      dependence of their reflected phase. This Letter describes how engineering the
      phase of PC mirrors enables sensors that are tolerant to variations in laser
      center frequency and line width. Reflection spectra measurements of Fabry-Perot
      cavities made with PC mirrors were collected as a function of wavelength and
      cavity length, providing experimental verification of theory and simulations. 

PMID- 24281493
TI  - Compressive sensing spectrometry based on liquid crystal devices.
AB  - We present a new type of compressive spectroscopy technique employing a liquid
      crystal (LC) phase retarder. A tunable LC cell is used in a manner compliant with
      the compressive sensing (CS) framework to significantly reduce the spectral
      scanning effort. The presented optical spectrometer consists of a single LC phase
      retarder combined with a single photo detector, where the LC phase retarder is
      used to modulate the input spectrum and the photodiode is used to measure the
      transmitted spectral signal. Sequences of measurements are taken, where each
      measurement is done with a different state of the retarder. Then, the set of
      photodiode measurements is used as input data to a CS solver algorithm. We
      demonstrate numerally compressive spectral sensing with approximately ten times
      fewer measurements than with an equivalent conventional spectrometer. 

PMID- 24281494
TI  - Increase of spatial coherence by subwavelength metallic gratings.
AB  - We study the coherence changes in partially coherent beams transmitted through
      binary metallic gratings. The interaction of Gaussian Schell-model beams with
      grating structures supporting surface plasmons is rigorously modeled using the
      Fourier modal method and the coherent mode representation of partially coherent
      fields. Our numerical results show that, by choosing suitable parameters for the
      grating, the degree of coherence of the beam can be significantly increased. The
      studied approach offers new possibilities to alter the coherence properties of
      fields using nanophotonic components. 

PMID- 24281495
TI  - Single-shot soft x-ray laser linewidth measurement using a grating
      interferometer.
AB  - The linewidth of a 14.7 nm wavelength Ni-like Pd soft x-ray laser was measured in
      a single shot using a soft x-ray diffraction grating interferometer. The
      instrument uses the time delay introduced by the gratings across the beam to
      measure the temporal coherence. The spectral linewidth of the 4d1S0-4p1P1 Ni-like
      Pd lasing line was measured to be Deltalambda/lambda=3*10(-5) from the Fourier
      transform of the fringe visibility. This single shot linewidth measurement
      technique provides a rapid and accurate way to determine the temporal coherence
      of soft x-ray lasers that can contribute to the development of femtosecond plasma
      based soft x-ray lasers.

PMID- 24281496
TI  - Generation of sub-30-fs microjoule mid-infrared pulses for ultrafast vibrational
      dynamics at solid/liquid interfaces.
AB  - We describe temporal compression of ultrabroadband, few microjoule mid-infrared
      (mid-IR) pulses from a noncollinear optical parametric amplifier (NOPA) employed
      in a sum-frequency generation (SFG) vibrational spectroscopic system, operating
      in total-internal-reflection geometry. The propagation of the mid-IR beam through
      optical materials results in a significant temporal chirp at the probed
      interface, which is analyzed and corrected by properly managing the total
      dispersion of materials introduced into the mid-IR beam path. By employing the
      simultaneous spatial and temporal focusing of the broadband infrared pulses at
      the probed interface, we achieve a sub-50-fs full width at half-maximum (FWHM)
      for the instrument response function, measured via SFG cross correlation of the
      ultrashort mid-IR pulses with an ultrashort (~30 fs) near-IR pulse from a
      synchronized, independently tunable NOPA. From the SFG cross-correlation FWHM, we
      extract a sub-30-fs mid-IR pulse duration, making it a suitable SFG spectroscopic
      system to investigate vibrational dynamics in hydrogen-bonded systems at
      interfaces.

PMID- 24281497
TI  - Target flux estimation by calculating intersections between neighboring conic
      reflector patches.
AB  - We propose a fast algorithm to estimate the flux collected by conic reflector
      patches, based on the calculation of intersections between neighboring patches.
      The algorithm can be employed in conjunction with the supporting ellipsoids
      algorithm for freeform reflector design and is shown to be orders of magnitude
      faster and more scalable than the commonly used Monte Carlo ray tracing approach.

PMID- 24281498
TI  - Effect of Kerr and resonant nonlinearities on phase locking of a multistable
      fiber amplifier array.
AB  - An analysis is presented, based on a rigorous solution of the propagation
      equations, of an array of saturable fiber amplifiers with scatter in length that
      is subject to global feedback. Passively phase-locked states exhibiting
      multistability due to resonant or Kerr nonlinearity are predicted in respectively
      low and high regimes of optical feedback. 

PMID- 24281499
TI  - Tailoring the hole-injection layer in organic light-emitting devices by
      introducing Au@SiO2 nanoparticles.
AB  - A simple and efficient method to improve the internal and external quantum
      efficiency of phosphorescent organic light-emitting devices (PhOLEDs) is
      demonstrated, i.e., combining the localized surface plasmon (LSP) and optical
      scattering effects by introducing gold nanoparticles (NPs) coated by SiO2 (named
      as Au@SiO2). The effects of LSP and optical scattering on PhOLEDs are studied.
      The lifetime of the triplet exciton in the device is modified by surface plasmon
      coupling induced by Au@SiO2 NPs, which results in increased internal quantum
      efficiency of the NP-containing devices. The optical scattering effect induced by
      Au@SiO2 NPs enhances the light outcoupling efficiency of the PhOLEDs and is
      demonstrated by measuring the angularly resolved photoluminescence. As a result,
      a PhOLED with 101% improved efficiency and 21% reduced efficiency roll-off is
      achieved using the composite HTL.

PMID- 24281500
TI  - Pr:YAlO3 laser generation in the green spectral range.
AB  - A continuous-wave 37 mW Pr:YAlO<subYAlO3 laser operating at 547 nm wavelength is
      reported. Microchip resonator geometry in connection with 1 W InGaN laser diode
      pumped, cryogenically cooled active medium was employed to achieve green laser
      emission.

PMID- 24281501
TI  - Erbium fiber laser-based direct frequency comb spectroscopy of Rb two-photon
      transitions.
AB  - We demonstrate the direct frequency comb spectroscopy of Rb 5S->5D two-photon
      transitions directly excited by an optical frequency comb (OFC) in 1.5 MUm fiber
      communication bands. A chain of comb spectral manipulation and quantum coherence
      control is implemented to enhance the efficiency of second harmonic OFC
      generation and eliminate the Doppler-broadening background. The direct frequency
      comb spectroscopy with clearly resolved transition lines is obtained. Our scheme
      provides a potential approach to realize the OFC at ~1.5 MUm with high stability
      and accuracy.

PMID- 24281502
TI  - Self-scattering effects in femtosecond laser nanoablation.
AB  - We experimentally investigate the self-reflectivity of intense strongly focused
      femtosecond laser pulses used for single-shot femtosecond laser ablation of
      silicon-on-insulator (SOI). We model the self-reflectivity using 2D finite
      difference time-domain simulations of a single femtosecond laser pulse
      interacting with a submicrometer-sized time- and space-dependent plasma induced
      by the incident pulse itself and find excellent agreement with our experimental
      results. The simulation shows that the laser-induced plasma scatters the incident
      pulse into the guided modes of the device layer of the SOI. 

PMID- 24281503
TI  - Photothermal nonlinearity and optical bistability in a graphene-silicon waveguide
      resonator.
AB  - We report observation of optical bistability and enhanced thermal nonlinearity in
      a graphene-silicon waveguide resonator. Photo-induced Joule heating in the
      graphene layer gives rise to a temperature increase in the silicon waveguide core
      and a corresponding thermo-optic shift in the resonance of the Fabry-Perot
      resonator. Measurement of the nonlinear resonance spectra showed a 9-fold
      increase in the effective thermal nonlinear index due to the graphene layer
      compared with a bare silicon waveguide. 

PMID- 24281504
TI  - Direct femtosecond pulse compression with miniature-sized Bragg cholesteric
      liquid crystal.
AB  - Direct compression of femtosecond optical pulses from a Ti:sapphire laser
      oscillator was realized with a cholesteric liquid crystal acting as a nonlinear
      1D periodic Bragg grating. With a 6 MUm thick sample, the pulse duration could be
      compressed from 100 to 48 fs. Coupled-mode equations for forward and backward
      waves were employed to simulate the dynamics therein, and good agreement between
      theory and experiment was obtained.

PMID- 24281505
TI  - Transition from nonresonant to resonant random lasers by the geometrical
      confinement of disorder.
AB  - We report on a transition in random lasers that is induced by the geometrical
      confinement of the emitting material. Different dye doped paper devices with
      controlled geometry are fabricated by soft lithography and show two distinguished
      behaviors in the stimulated emission: in the absence of boundary constraints, the
      energy threshold decreases for larger laser volumes showing the typical trend of
      diffusive nonresonant random lasers, while when the same material is lithographed
      into channels, the walls act as cavity and the resonant behavior typical of
      standard lasers is observed. The experimental results are consistent with the
      general theories of random and standard lasers and a clear phase diagram of the
      transition is reported. 

PMID- 24281506
TI  - Buffering and trapping ultrashort optical pulses in concatenated Bragg gratings.
AB  - Strong retardation of ultrashort optical pulses, including their deceleration and
      stoppage in the form of Bragg solitons in a cascaded Bragg grating (BG)
      structure, is proposed. The manipulations of the pulses are carried out, using
      nonlinear effects, in a chirped BG segment which is linked, via a defect, to a
      uniform grating. The storage of the ultrashort pulses is shown to be very robust
      with respect to variations of the input field intensity, suggesting the
      feasibility of storing ultrafast optical pulses in such a structure. Physical
      estimates are produced for the BGs written in silicon. 

PMID- 24281507
TI  - Generation of high-photon flux-coherent soft x-ray radiation with few-cycle
      pulses.
AB  - We present a tabletop source of coherent soft x-ray radiation with high-photon
      flux. Two-cycle pulses delivered by a fiber-laser-pumped optical parametric
      chirped-pulse amplifier operating at 180 kHz repetition rate are upconverted via
      high harmonic generation in neon to photon energies beyond 200 eV. A maximum
      photon flux of 1.3.10(8) photons/s is achieved within a 1% bandwidth at 125 eV
      photon energy. This corresponds to a conversion efficiency of ~10(-9), which can
      be reached due to a gas jet simultaneously providing a high target density and
      phase matching. Further scaling potential toward higher photon flux as well as
      higher photon energies are discussed.

PMID- 24281508
TI  - ITO/Ag/ITO multilayer-based transparent conductive electrodes for ultraviolet
      light-emitting diodes.
AB  - ITO/Ag/ITO (IAI) multilayer-based transparent conductive electrodes for
      ultraviolet light-emitting diodes are fabricated by reactive sputtering,
      optimized by annealing, and characterized with respect to electrical and optical
      properties. Increasing the annealing temperature from 300 degrees C to 500
      degrees C decreased the sheet resistance and increased the transmittance. This
      may result from an observed improvement in the crystallinity of the IAI
      multilayer and a reduction in the near-UV absorption coefficient of Ag. We
      observed the lowest sheet resistance (9.21 Omega/sq) and the highest optical
      transmittance (88%) at 380 nm for the IAI multilayer samples annealed in N2 gas
      at 500 degrees C.

PMID- 24281509
TI  - Imaging of photonic modes in an AlN-based photonic crystal probed by an ultra
      violet internal light source.
AB  - The spatial distribution of photon modes confined in a 0D cavity and a 1D W1
      waveguide is investigated on AlN-based photonic crystal (PC) membranes by
      spectrally resolved scanning confocal microscopy in the ultra-violet spectral
      range. The influence of the fabrication-induced disorder of the PC on the photon
      modes is analyzed. The cavity modes are shown to be robust with respect to
      disorder, whereas the 1D modes of the W1 waveguide are localized near its cut-off
      frequency. Those modifications of the lowest energy photonic modes are compared
      to simulations of weakly disordered photonic structures. 

PMID- 24281510
TI  - Generation of correlated photon pairs in micro/nano-fibers.
AB  - We study the generation of correlated photon pairs via spontaneous four-wave
      mixing (SFWM) in a 15 cm long micro/nano-fiber (MNF). The MNF is properly
      fabricated to satisfy the phase-matching condition for generating the signal and
      idler photon pairs at wavelengths of about 1310 and 851 nm, respectively. Photon
      counting measurements yield a coincidence-to-accidental ratio of 530 for a photon
      production rate of about 0.002 (0.0005) per pulse in the signal (idler) band. We
      also analyze the spectral information of the signal photons originating from SFWM
      and Raman scattering (RS). In addition to discovering some unique features of RS,
      we find the bandwidth of the individual signal photons is much greater than the
      calculated value for the MNF with homogeneous structure. Our investigations
      indicate the MNF is a promising candidate for developing the sources of
      nonclassical light and the spectral property of photon pairs can be used to
      noninvasively test the diameter and homogeneity of the MNF.

PMID- 24281511
TI  - Terahertz wire grid polarizer fabricated by imprinting porous silicon.
AB  - A terahertz (THz) wire-grid polarizer is fabricated by imprinting porous Si
      followed by oblique evaporation of Ag. We demonstrate that it works in a wide
      frequency region covering from 5 to 18 THz with the extinction ratio of 10 dB.
      The frequency region is much wider than that of THz wire-grid polarizers
      fabricated by conventional imprint lithography using organic materials. The
      result suggests that imprinting of porous Si is a promising fabrication technique
      to realize low-cost wire-grid polarizers working in the THz region.

PMID- 24281512
TI  - Ultra-broadband performance enhancement of thin-film amorphous silicon solar
      cells with conformal zig-zag configuration.
AB  - An ultrathin amorphous silicon solar cell with conformal zig-zag
      nanoconfiguration is studied from both light-trapping and light-conversion
      perspectives. The design improves the front antireflection property, optimizes
      the rear metallic reflector, and elongates the optical path inside the
      photoactive layer. Compared to conventional nanoconfigurations, this system shows
      significant absorption enhancement in the whole amorphous silicon band and
      exhibits extremely low sensitivity to light polarization. The nano-optimization
      indicates that the short-circuit current density (light-conversion efficiency) of
      the 200-nm-thick solar cell can be 16.88 mA/cm2 (13.38%), showing an enhancement
      factor of 32.90% (33.53%) from the planar system.

PMID- 24281513
TI  - Adaptive optical two-photon microscopy using autofluorescent guide stars.
AB  - We demonstrate a fast, direct wavefront-sensing method for dynamic in vivo
      adaptive optical two-photon microscopy. By using a Shack-Hartmann wavefront
      sensor and open-loop control, the system provides high-speed wavefront
      measurement and correction. To measure the wavefront in the middle of a
      Drosophila embryo at early stages, autofluorescence from endogenous fluorophores
      in the yolk were used as reference guide stars. The method was tested through
      live imaging of a Drosophila embryo. The aberration in the middle of the embryo
      was measured directly for the first time. After correction, the contrast and
      signal intensity of the structure in the middle of the embryo was improved. 

PMID- 24281514
TI  - Active linewidth-narrowing of a mid-infrared quantum cascade laser without
      optical reference.
AB  - We report on a technique for frequency noise reduction and linewidth-narrowing of
      a distributed-feedback mid-IR quantum cascade laser (QCL) that does not involve
      any optical frequency reference. The voltage fluctuations across the QCL are
      sensed, amplified and fed back to the temperature of the QCL at a fast rate using
      a near-IR laser illuminating the top of the QCL chip. A locking bandwidth of 300
      kHz and a reduction of the frequency noise power spectral density by a factor of
      10 with respect to the free-running laser are achieved. From 2 MHz for the free
      running QCL, the linewidth is narrowed below 700 kHz (10 ms observation time).

PMID- 24281515
TI  - Tunable supercontinuum light vector vortex beam generator using a q-plate.
AB  - Spatially coherent multicolored optical vector vortex beams were created using a
      tunable liquid crystal q-plate and a supercontinuum light source. The feasibility
      of the q-plate as a tunable spectral filter (switch) was demonstrated, and the
      polarization topology of the resulting vector vortex beam was mapped. Potential
      applications include multiplexing for broadband high-speed optical communication,
      ultradense data networking, and super-resolution microscopy. 

PMID- 24281516
TI  - Injection locking of two frequency-doubled lasers with 3.2 GHz offset for driving
      Raman transitions with low photon scattering in 43Ca+.
AB  - We describe the injection locking of two infrared (794 nm) laser diodes that are
      each part of a frequency-doubled laser system. An acousto-optic modulator in the
      injection path gives an offset of 1.6 GHz between the lasers for driving Raman
      transitions between states in the hyperfine split (by 3.2 GHz) ground level of
      43Ca+. The offset can be disabled for use in 40Ca+. We measure the relative
      linewidth of the frequency-doubled beams to be 42 mHz in an optical heterodyne
      measurement. The use of both injection locking and frequency doubling combines
      spectral purity with high optical power. Our scheme is applicable for providing
      Raman beams across other ion species and neutral atoms where coherent optical
      manipulation is required.

PMID- 24281517
TI  - Yb:KYW planar waveguide laser Q-switched by evanescent-field interaction with
      carbon nanotubes.
AB  - We report Q-switched operation of a planar waveguide laser by evanescent-field
      interaction with single-walled carbon nanotubes deposited on top of the
      waveguide. The saturable-absorber-integrated gain medium, which operates based on
      evanescent-field interaction, enables the realization of a diode-pumped 2.5-cm
      long Q-switched Yb:KYW waveguide laser emitting at 1030 nm. With such a compact
      cavity design, we achieve maximum output powers of up to 30 mW, corresponding to
      a single-pulse energy of 124 nJ, at 241 kHz repetition rate. The shortest pulse
      duration of 433 ns is generated at a repetition rate of 231 kHz.

PMID- 24281518
TI  - Infrared imaging in liquid through an extrinsic optical microcavity.
AB  - The mutual interference of light scattered inside an extrinsic Fabry-Perot
      microcavity, fed by a low-coherence light, is exploited to achieve infrared
      imaging in a liquid environment. The transverse field distribution inside a
      cavity is shaped by the effect of scattered interfering waves in a lens-free
      system. Reflectivity and contrast phase maps are extracted through the analysis
      of the cavity response in the time domain. This approach allows to conjugate
      noninvasivity, subdiffraction imaging, possible quantitative evaluation of
      dielectric constants and infrared spectroscopy, making it suitable for biological
      applications. 

PMID- 24281519
TI  - Dark solitons in the presence of higher-order effects.
AB  - Dark soliton propagation is studied in the presence of higher-order effects,
      including third-order dispersion, self-steepening, linear/nonlinear gain/loss,
      and Raman scattering. It is found that for certain values of the parameters a
      stable evolution can exist for both the soliton and the relative continuous-wave
      background. Using a newly developed perturbation theory we show that the
      perturbing effects give rise to a shelf that accompanies the soliton in its
      propagation. Although, the stable solitons are not affected by the shelf it
      remains an integral part of the dynamics otherwise not considered so far in
      studies of higher-order nonlinear Schrodinger models. 

PMID- 24281520
TI  - Scattering of inhomogeneous plane waves by a resistive half-screen.
AB  - The scattering process of inhomogeneous plane waves by a resistive half-plane is
      investigated by using the exact diffracted field expressions. The uniform field
      representations are obtained with the aid of the uniform theory, put forward by
      Umul. The geometrical optics and diffracted and scattered fields are examined
      numerically. 

PMID- 24281521
TI  - High-energy terahertz pulses from organic crystals: DAST and DSTMS pumped at
      Ti:sapphire wavelength.
AB  - High-energy terahertz pulses are produced by optical rectification (OR) in
      organic crystals 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) and 4-N,
      N-dimethylamino-4'-N'-methyl-stilbazolium 2,4,6-trimethylbenzenesulfonate (DSTMS)
      by a Ti:sapphire amplifier system with 0.8 MUm central wavelength. The simple
      scheme provides broadband spectra between 1 and 5 THz, when pumped by a
      collimated 60 fs near-IR pump pulse, and it is scalable in energy. Fluence
      dependent conversion efficiency and damage threshold are reported, as well as
      optimized OR at visible wavelengths.

PMID- 24281522
TI  - Femtosecond-laser pumped CdSiP2 optical parametric oscillator producing 100 MHz
      pulses centered at 6.2 MUm.
AB  - We report the first, to the best of our knowledge, femtosecond-laser-pumped
      optical parametric oscillator (OPO) based on the newly developed nonlinear
      crystal, CdSiP2. The OPO was synchronously pumped by a mode-locked
      Yb:KYW/Yb:fiber master-oscillator power amplifier, providing 1.053 MUm pump
      pulses with durations of 130 fs at a repetition rate of 100 MHz. The 0.5-mm-thick
      CdSiP2 crystal was cut for a type-I noncritical interaction, providing a broad
      phase-matching bandwidth and ensuring excellent temporal overlap among the pump,
      signal, and idler pulses. The OPO generated signal pulses with a spectral
      coverage over 1260-1310 nm and mid-infrared idler pulses with a broad spectral
      coverage at 5.8-6.6 MUm (6.2 THz). With a 2% output coupler (OC), the threshold
      pump power was 600 mW. At the maximum pump power of 1.6 W, 0.55 W was absorbed
      due to two-photon absorption and residual linear absorption in the CdSiP2
      crystal, 0.75 W was transmitted, and 53 mW signal power was extracted through the
      OC. We estimate that the generated idler power was 24 mW.

PMID- 24281523
TI  - Stable, continuous-wave, ytterbium-fiber-based single-pass ultraviolet source
      using BiB3O6.
AB  - We report stable continuous-wave (CW) ultraviolet (UV) generation at 354.7 nm
      using single-pass sum-frequency-generation (SFG) of a CW Yb-fiber laser at 1064
      nm in the nonlinear crystal, BiB3O6. The 532 nm radiation is obtained by single
      pass second-harmonic generation of the Yb-fiber laser in a 30-mm-long MgO:sPPLT
      crystal. Using a 10-mm-long BiB3O6 crystal for SFG, with a measured angular
      acceptance bandwidth of 0.57 mrad, we generate as much as 68 mW of CW single
      frequency UV radiation with a passive power stability better than 3.2% rms over 2
      h and frequency stability better than 436 MHz over 2.5 h. The UV output beam has
      a TEM00 spatial profile with M(x)(2)<1.6 and M(y)(2)<1.8.

PMID- 24281524
TI  - Reconfigurable switching of orbital-angular-momentum-based free-space data
      channels.
AB  - Light beams can carry orbital angular momentum (OAM) such that a helical phase
      front twists along the direction of propagation. OAM beams have been demonstrated
      in a wide variety of applications and have been found to offer a new orthogonal
      degree of freedom for multiplexing independent data streams for high-capacity
      point-to-point optical communications. However, to enable their efficient use in
      reconfigurable networks, approaches must be developed to manipulate OAM beams. We
      demonstrate OAM-based reconfigurable optical switching functions among multiple
      OAM beams. Selective data switching among three 100 Gb/s quadrature phase-shift
      keying OAM channels was achieved with a 2.1 dB optical signal-to-noise ratio
      penalty. The scheme of selective OAM-beam manipulation can be potentially
      cascaded to realize an arbitrary n*n switching function.

PMID- 24281525
TI  - Generation of two-cycle pulses and octave-spanning frequency combs in a
      dispersion-flattened micro-resonator.
AB  - We show that octave-spanning Kerr frequency combs with improved spectral flatness
      of comb lines can be generated in dispersion-flattened microring resonators. The
      resonator is formed by a strip/slot hybrid waveguide, exhibiting a flat and low
      anomalous dispersion between two zero-dispersion wavelengths that are separated
      by one octave from near-infrared to mid-infrared. Such flattened dispersion
      profiles allow for the generation of mode-locked frequency combs, using
      relatively low pump power to obtain two-cycle cavity solitons on a chip,
      associated with the octave-spanning comb bandwidth. The wavelength dependence of
      the optical loss and of the coupling coefficient and thus wavelength dependent Q
      factor are also considered. 

PMID- 24281526
TI  - Optimized x-ray multilayer mirrors for single nanometer focusing.
AB  - We present numerical simulations optimizing the layer shapes of curved focusing x
      ray multilayer mirrors deployed at synchrotron radiation facilities using a wave
      optical model. The confocal elliptical shapes of the inner layers are corrected
      for refraction based on the modified Bragg law. Simulated wave amplitudes are
      further propagated to the focal region, promising nanometer focusing. 

PMID- 24281527
TI  - Nonuniform sampled scalar diffraction calculation using nonuniform fast Fourier
      transform.
AB  - Scalar diffraction calculations, such as the angular spectrum method (ASM) and
      Fresnel diffraction, are widely used in the research fields of optics, x rays,
      electron beams, and ultrasonics. It is possible to accelerate the calculation
      using fast Fourier transform (FFT); unfortunately, acceleration of the
      calculation of nonuniform sampled planes is limited due to the property of the
      FFT that imposes uniform sampling. In addition, it gives rise to wasteful
      sampling data if we calculate a plane having locally low and high spatial
      frequencies. In this Letter, we developed nonuniform sampled ASM and Fresnel
      diffraction to improve the problem using the nonuniform FFT. 

PMID- 24281528
TI  - Optical trapping of red blood cells in living animals with a water immersion
      objective.
AB  - We demonstrate optical trapping of red blood cells (RBCs) in living animals by
      using a water immersion objective. First, the cells within biological tissue are
      mimicked by the particles immersed in aqueous solutions of glycerol. The optical
      forces depending on trapping depth are investigated when a parallel laser beam
      enters the water immersion objective. The results show that the optical forces
      vary with trapping depth, and the optimal trapping depth in aqueous solutions of
      glycerol (n=1.39) is 50 MUm. Second, the optimal trapping depth in aqueous
      solutions of glycerol can be changed by altering the actual tube length of the
      water immersion objective. Finally, we achieved optical trapping and manipulation
      of RBCs in living mice.

PMID- 24281529
TI  - Enhanced spontaneous backscattering in Brillouin dynamic gratings.
AB  - Spontaneous Brillouin backscattering, which accompanies the operation of
      Brillouin dynamic gratings (BDGs) setups, is investigated both theoretically and
      experimentally. It is shown that this noisy emission, which cannot be separated
      from the signal of interest, contains not only the probe spontaneous Brillouin
      backscattering but also a significant contribution from the
      spontaneous/stimulated acoustic field, originating from the high-frequency
      writing pump. In the absence of the low-frequency writing pump and for a strong
      enough high-frequency writing pump, the observed Stokes noise can exhibit an
      average backscattered power much higher than that from the probe alone. 

PMID- 24281530
TI  - Liquid-crystal-on-silicon-based optical add/drop multiplexer for orbital-angular
      momentum-multiplexed optical links.
AB  - We designed an optical add/drop multiplexer for orbital-angular-momentum (OAM)
      multiplexed data links by taking advantage of the ring-shaped intensity profile
      of OAM beams. We demonstrated adding/dropping a single OAM beam from three
      multiplexed OAM beams using liquid-crystal-on-silicon-based diffraction optical
      elements. For multiplexed OAM beams carrying 100 Gbit/s quadrature phase-shift
      keying data, a power penalty of <2 dB is observed to achieve a bit-error rate of
      2.0*10(-3) for each channel of the add/drop multiplexer.

PMID- 24281531
TI  - Unsupervised change detection of satellite images using low rank matrix
      completion.
AB  - Traditional unsupervised change detection methods need to generate a difference
      image (DI) for subsequent processing to produce a binary change map. In addition,
      few methods explore global structures. This Letter presents a novel unsupervised
      change detection approach based on low rank matrix completion. Other than
      generating a DI, the changed pixels are modeled as the estimated missing values
      for matrix completion, where the changed pixels are represented by a sparse term.
      A common low rank matrix is recovered by two temporal images. The changed pixels
      are separated out from the low rank matrix, in which the local information is
      introduced via graph cuts. The global and local structures are utilized in our
      model. Experimental results validate the effectiveness of the proposed approach.
      The proposed method is a new view for change detection. 

PMID- 24281532
TI  - Mutual injection phase locking coherent combination of solid-state lasers based
      on corner cube.
AB  - Coherent beam combination is an effective way to develop high-power lasers with
      high beam quality and high brightness. Coherent combination of six solid-state
      lasers based on the technique of mutual injection phase locking by using the
      natural coherent combination property of corner cube is first investigated. The
      coherent combination with 15.3 J of output energy, 1.7 mrad of divergent angle is
      obtained, and the combining efficiency is as high as 95.6% at 10 Hz and 85 A. The
      far-field profile is flattened protuberance.

PMID- 24281533
TI  - Light scattering by randomly irregular dielectric particles larger than the
      wavelength.
AB  - We present results of simulation of light scattering by randomly irregular
      particles that have dimensions larger than the wavelength of incident light. We
      apply the discontinuous Galerkin time domain method and compare the accurate
      solution with that obtained using an approximate geometric-optics model. A
      qualitative agreement is observed for scattering angle curves of intensity at the
      size parameter of X=60, whereas angular dependence of polarization appears to be
      more sensitive to the wave effects and requires larger sizes for application of
      geometrical optics. 

PMID- 24281534
TI  - Single-shot visualization of evolving, light-speed structures by multiobject
      plane phase-contrast imaging.
AB  - We demonstrate a single-shot method of visualizing the evolution of light-speed,
      laser-generated structures as they propagate over hundreds of Rayleigh lengths
      (typically >=10 cm) through a tenuous medium. An ultrashort probe pulse crosses
      the object's path at a small angle (theta<5 degrees ) and a specific time delay.
      Copies of the phase-modulated probe are then relay-imaged to separate detectors
      from selected object planes along the propagation path. A phase-contrast
      technique based on Kerr effect and nonlinear absorption converts phase to
      intensity modulation, improving sensitivity in tenuous media. A continuous record
      of the probe phase modulation along the propagation path is reconstructed.

PMID- 24281535
TI  - Invariance of optimal composite waveguide geometries with respect to permittivity
      of the metal cladding.
AB  - We optimize the threshold gain for cylindrical composite (semiconductor
      dielectric-metal) waveguides (WGs) with various metal claddings. We show that the
      optimal dielectric width is invariant with respect to the imaginary part of the
      permittivity of the metal, epsilonM'', and weakly dependent on the real part,
      epsilonM'. To explain this behavior, we compare optimal geometries of WGs with
      different semiconductor permittivities, epsilonG'. Results from these comparisons
      indicate that the optimal effective index parallels the optimal threshold gain in
      its relation to epsilonM. We use our results to heuristically propose an
      analytical expression for the optimal threshold gain that approximates the
      numerical solution to within a factor of two over the range of explored
      epsilonG'. Finally, we use data from our optimizations to obtain approximate
      analytical expressions for the optimal dielectric width and threshold gain as
      functions of the total WG radius.

PMID- 24281536
TI  - Influence of self-focusing of ultrashort laser pulses on optical third-harmonic
      generation at interfaces.
AB  - We report on the third-harmonic generation of femtosecond laser pulses at
      interfaces. We measured slabs of different types of optical glasses and
      demonstrated that the asymmetric intensity profile observed for a tightly focused
      beam can be explained by self-focusing effects. 

PMID- 24281537
TI  - Radial Hilbert transform with the spatially variable half-wave plate.
AB  - We analyzed the point spread function (PSF) of the typical 4f optical image
      processing system by use of a spatially variable half-wave plate as the spatial
      filter and found that the PSF is an elementary vector beam. Theoretical analysis
      and real experiments show that the optical system can be used for a radially
      symmetric Hilbert transform that permits two-dimensional edge enhancement as the
      spiral phase plate. This kind of radial Hilbert transform is useful for image
      processing because it can enhance the edges of an input image selectively by
      exerting a polarization analyzer before the output plane. The optical system also
      can be used for generation of vector beams with arbitrary array and shape in real
      time conveniently. 

PMID- 24281538
TI  - Fast calculation method for computer-generated cylindrical holograms based on the
      three-dimensional Fourier spectrum.
AB  - The relation between a three-dimensional (3D) object and its diffracted wavefront
      in the 3D Fourier space is discussed at first and then a rigorous diffraction
      formula onto cylindrical surfaces is derived. The azimuthal direction and the
      spatial frequency direction corresponding to height can be expressed with a one
      dimensional (1D) convolution integral and a 1D inverse Fourier transform in the
      3D Fourier space, respectively, and fast Fourier transforms are available for
      fast calculation. A numerical simulation of a diffracted wavefront on cylindrical
      surfaces is presented. An alternative optical experiment equivalent of the
      optical reconstruction from cylindrical holograms is also demonstrated. 

PMID- 24281539
TI  - Bidirectional multiplexing of heralded single photons from a silicon chip.
AB  - We demonstrate integrated spatial multiplexing of heralded single photons
      generated from a single 96 MUm long silicon photonic crystal waveguide in a
      bidirectional pump configuration. By using a low-loss fiber-coupled opto-ceramic
      switch, the multiplexing technique enhances the brightness of the single photon
      source by 51.2+/-4.0% while maintaining the coincidence-to-accidental ratio.
      Compared with the demonstration of multiplexing two individual sources, the
      bidirectional pump scheme represents a twofold reduction in the footprint of
      nonlinear devices for future large-scale integration of on-chip single photon
      sources. The 51.2+/-4.0% gain will make any quantum operation requiring n photons
      1.5(n) times faster.

PMID- 24281540
TI  - Sub-100-fs Yb:CALGO nonlinear regenerative amplifier.
AB  - We report on the first diode-pumped Yb:CaGdAlO4 regenerative amplifier in the sub
      100-fs regime. It generates pulses at a central wavelength of 1047 nm with up to
      24 MUJ energy (after compression) at a repetition rate of 50 kHz. The measured
      pulse duration is 97 fs, with a spectral bandwidth of 19 nm. We describe in
      detail how nonlinear effects are optimally used to compensate gain narrowing in
      order to overcome the 100 fs barrier.

PMID- 24281541
TI  - Topical dual-stain difference imaging for rapid intra-operative tumor
      identification in fresh specimens.
AB  - Assessing tumor margin status during surgery is critical to ensure complete
      resection of cancer tissue; however, current approaches are ineffective and often
      result in repeat surgery. We present an optical imaging approach for margin
      assessment using topical application of two fluorescent stains, one targeted to a
      tumor biomarker and the other a nontargeted reference, to freshly excised
      specimens. Computing a normalized difference image from fluorescence images of
      the targeted and untargeted stains suppresses the confounding effects of
      nonspecific uptake. Applying this approach in excised breast tumor models
      produced promising tumor-to-normal tissue contrasts that were significantly
      higher than single-targeted-stain imaging. 

PMID- 24281542
TI  - Improving visibility in photoacoustic imaging using dynamic speckle illumination.
AB  - In high-frequency photoacoustic imaging with uniform illumination, homogeneous
      photoabsorbing structures may be invisible because of their large size or limited
      view issues. Here we show that, by exploiting dynamic speckle illumination, it is
      possible to reveal features that are normally invisible with a photoacoustic
      system comprised of a 20 MHz linear ultrasound array. We demonstrate imaging of a
      ?5 mm absorbing cylinder and a 30 MUm black thread arranged in a complex shape.
      The hidden structures are directly retrieved from photoacoustic images recorded
      for different random speckle illuminations of the phantoms by assessing the
      variation in the value of each pixel over the illumination patterns.

PMID- 24281543
TI  - Raman mediated all-optical cascadable inverter using silicon-on-insulator
      waveguides.
AB  - In this Letter, we propose an all-optical circuit for a cascadable and integrable
      logic inverter based on stimulated Raman scattering. A maximum product criteria
      for noise margin is taken to analyze the cascadability of the inverter. Variation
      of noise margin for different model parameters is also studied. Finally, the time
      domain response of the inverter is analyzed for different widths of input pulses.

PMID- 24281544
TI  - Single-shot self-interference incoherent digital holography using off-axis
      configuration.
AB  - We propose a single-shot incoherent holographic imaging technique that adopts
      self-interference incoherent digital holography (SIDH) with slight tilt of the
      plane mirror in the optical configuration. The limited temporal coherence length
      of the illumination leads the guide-star hologram of the proposed system to have
      a Gaussian envelope of elliptical ring shape. The observation shows that the
      reconstruction by cross correlation with the guide-star hologram achieves better
      quality than the usual propagation methods. Experimentally, we verify that the
      hologram and 3D reconstruction can be implemented incoherently with the proposed
      single-shot off-axis SIDH. 

PMID- 24281545
TI  - Sub-bandgap linear-absorption-based photodetectors in avalanche mode in PN-diode
      integrated silicon microring resonators.
AB  - We report a sub-bandgap linear-absorption-based photodetector in avalanche mode
      at 1550 nm in a PN-diode-integrated silicon microring resonator. The photocurrent
      is primarily generated by the defect-state absorption introduced by the boron and
      phosphorous ion implantation during the PN diode formation. The responsivity is
      enhanced by both the cavity effect and the avalanche multiplication. We measure a
      responsivity of ~72.8 mA/W upon 8 V at cavity resonances in avalanche mode,
      corresponding to a gain of ~72 relative to the responsivity of ~1.0 mA/W upon 3 V
      at cavity resonances in normal mode. Our device exhibits a 3 dB bandwidth of ~7
      GHz and an open eye diagram at 15 Gbit/s upon 8 V.

PMID- 24281546
TI  - Antagonistic selection factors induce a continuous population divergence in a
      polymorphism.
AB  - Understanding the relative importance of selection and stochastic factors in
      population divergence of adaptive traits is a classical topic in evolutionary
      biology. However, it is difficult to separate these factors and detect the
      effects of selection when two or more contrasting selective factors are
      simultaneously acting on a single locus. In the damselfly Ischnura senegalensis,
      females exhibit color dimorphism and morph frequencies change geographically. We
      here evaluated the role of selection and stochastic factors in population
      divergence of morph frequencies by comparing the divergences in color locus and
      neutral loci. Comparisons between population pairwise FST for neutral loci and
      for the color locus did not detect any stochastic factors affecting color locus.
      Although comparison between population divergence in color and neutral loci using
      all populations detected only divergent selection, we detected two antagonistic
      selective factors acting on the color locus, that is, balancing and divergent
      selection, when considering geographical distance between populations. Our
      results suggest that a combination of two antagonistic selective factors, rather
      than stochastic factors, establishes the geographic cline in morph frequency in
      this system. 

PMID- 24281547
TI  - Phylogeny and vicariant speciation of the Grey Rhebok, Pelea capreolus.
AB  - A South African endemic antelope, the Grey Rhebok (Pelea capreolus), has long
      been an evolutionary enigma in bovid systematics-its phylogenetic intractability
      attributed to its curious combination of derived and primitive morphological
      attributes and the consequences of a rapid radiation. By using a combination of
      DNA sequences, chromosomal characteristics and quantitative and qualitative
      morphological features we show that the species is a sister taxon to a clade that
      comprises the waterbuck, reedbuck and allies. Our finding of few unambiguous
      synapomorphies reinforces suggestions of a rapid radiation and highlights the
      effects of incomplete lineage sorting, including the hemiplasic nature of several
      chromosomal rearrangements. We investigate these data to address the general
      question of what may have led to Pelea being both genetically and ecologically
      distinct from the Reduncini. We argue that its adaptation to exposed habitats,
      free of standing water, arose by vicariance prompted by increasing aridity of the
      extreme south/southwestern region of the African continent in the Miocene.
      Ancestral lineages leading to the extant Redunca and Kobus, on the other hand,
      retreated to water-abundant refugia in the north during these mostly globally
      cool phases. The mosaic of water-rich environments provided by the Okavango and
      the drainage systems in the southwestern extension of the East African Rift
      system are considered to have facilitated speciation and chromosomal evolution
      within these antelope. 

PMID- 24281549
TI  - Is the post-disturbance composition of a plant population determined by selection
      for outcrossed seedlings or by the composition of the seedbank?
AB  - Seedbanks are expected to buffer populations against disturbances, such as fire,
      that could alter the genetic composition of smaller, ephemeral adult populations.
      However, seedling genotypes may be influenced by the spatially heterogeneous
      nature of both the seedbank and the disturbance (for example, germination may
      vary with local disturbance) and also by selection acting on germination and post
      germination performance. We used microsatellite-DNA surveys of seedlings emerging
      from the soil-stored seedbanks of Grevillea macleayana after wildfire to compare
      diversity and spatial structure in seedlings and adults, and through resampling
      of the seedling data set, to determine whether the resultant adult population
      reflected the effects of selection or random seedling mortality. The large post
      fire seedling cohorts captured the full allelic diversity of the pre-fire adult
      population. However, we found a mismatch in the genotypic structure of adults and
      seedlings. Seedlings displayed larger heterozygous deficits than adults; however,
      over the ensuing 11 years, seedling heterozygosity eventually matched values for
      the pre-fire adults. Increasing heterozygosity among adults has generally been
      attributed to heterosis and/or reduction in Wahlund effects via self-thinning.
      Resampling of early post-fire seedlings to generate samples of equivalent size to
      survivors at 11 years showed that increases in heterozygosity must be driven by
      selection favouring outcrossed seed. This finding is important in an evolutionary
      context but also has implications for the restoration of natural or managed
      populations where a seedbank is a viable source of recruits. 

PMID- 24281550
TI  - Aggregation-induced emission of GFP-like chromophores via exclusion of solvent
      solute hydrogen bonding.
AB  - The fluorescence of GFP-like chromophores in aqueous solutions is turned on upon
      forming aggregates or embedment in cell membranes as a result of exclusion of
      solvent-solute H-bonding. 

PMID- 24281548
TI  - Male killing Spiroplasma protects Drosophila melanogaster against two parasitoid
      wasps.
AB  - Maternally transmitted associations between endosymbiotic bacteria and insects
      are diverse and widespread in nature. Owing to imperfect vertical transmission,
      many heritable microbes have evolved compensational mechanisms to enhance their
      persistence in host lineages, such as manipulating host reproduction and
      conferring fitness benefits to host. Symbiont-mediated defense against natural
      enemies of hosts is increasingly recognized as an important mechanism by which
      endosymbionts enhance host fitness. Members of the genus Spiroplasma associated
      with distantly related Drosophila hosts are known to engage in either
      reproductive parasitism (i.e., male killing) or defense against natural enemies
      (the parasitic wasp Leptopilina heterotoma and a nematode). A male-killing strain
      of Spiroplasma (strain Melanogaster Sex Ratio Organism (MSRO)) co-occurs with
      Wolbachia (strain wMel) in certain wild populations of the model organism
      Drosophila melanogaster. We examined the effects of Spiroplasma MSRO and
      Wolbachia wMel on Drosophila survival against parasitism by two common wasps,
      Leptopilina heterotoma and Leptopilina boulardi, that differ in their host ranges
      and host evasion strategies. The results indicate that Spiroplasma MSRO prevents
      successful development of both wasps, and confers a small, albeit significant,
      increase in larva-to-adult survival of flies subjected to wasp attacks. We
      modeled the conditions under which defense can contribute to Spiroplasma
      persistence. Wolbachia also confers a weak, but significant, survival advantage
      to flies attacked by L. heterotoma. The host protective effects exhibited by
      Spiroplasma and Wolbachia are additive and may provide the conditions for such
      cotransmitted symbionts to become mutualists. Occurrence of Spiroplasma-mediated
      protection against distinct parasitoids in divergent Drosophila hosts suggests a
      general protection mechanism. 

PMID- 24281551
TI  - Wide band gap diketopyrrolopyrrole-based conjugated polymers incorporating
      biphenyl units applied in polymer solar cells.
AB  - Incorporating biphenyls as co-monomers in electron-deficient diketopyrrolopyrrole
      (DPP) conjugated polymers enables widening the optical band gap to 1.70 eV. Power
      conversion efficiencies of 3.7-5.7% and high open-circuit voltages of 0.80-0.93 V
      are obtained in solar cells based on these wide band gap DPP polymers. 

PMID- 24281552
TI  - Synthesis of Li/OR phosphinidenoid complexes: on the evidence for intramolecular
      O-Li donation and the effect of cation encapsulation.
AB  - Synthesis of phosphinite complexes 12-14a-c, 15a and 16a was achieved via
      reaction of transient Li/Cl phosphinidenoid complexes 6-10, prepared from
      dichloro(organo)phosphane complexes [(OC)5M{RPCl2}] 1-5 (1,6: R = CPh3, 2,7: R =
      C5Me5, 3-5, 8-10: R = CH(SiMe3)2, 1-3, 6-8: M = W, 9: M = Mo, 10: M = Cr), with
      different alcohols 11a-c (a: R = allyl, b: R = methyl, c: R = isopropyl).
      Deprotonation of complexes 12b, 13b with MeLi or (t)BuLi in the presence of two
      equivalents of 12-crown-4 led to the selective formation of phosphinidenoid
      complexes [Li(12-crown-4)2] [(OC)5W{RP(OCH3)}] (18a R = CPh3 and 18b R = C5Me5)
      which were stable in solution at ambient temperature, in contrast to Li/OMe
      phosphinidenoid complexes without 12-crown-4. To our surprise attempts to
      crystallise complex 18b yielded complex 21 having a Li-O-P subunit. The reaction
      of complex 17c with [Ph3C]BF4 yielded the P-C coupling product 26 and, hence, the
      first evidence for an oxidative SET reaction. All isolated products were
      characterised by multinuclear NMR spectroscopy, IR, MS and single-crystal X-ray
      crystallography in the case of complexes 12a,b, 13b, 14a-c, 15a, 16a and 21.

PMID- 24281553
TI  - Improving the gas barrier property of clay-polymer multilayer thin films using
      shorter deposition times.
AB  - Relatively fast exposure times (5 s) to aqueous solutions were found to improve
      the gas barrier of clay-polymer thin films prepared using layer-by-layer (LbL)
      assembly. Contrary to the common belief about deposition time (i.e., the longer
      the better), oxygen transmission rates (OTRs) of these nano-brick-wall assemblies
      are improved by reducing exposure time (from 1 min to 5 s). Regardless of
      composition, LbL films fabricated using shorter deposition time are always
      thicker in the first few layers, which correspond to greater clay spacing and
      lower OTR. A quadlayer (QL) assembly consisting of three repeat units of branched
      polyethylenimine (PEI), poly(acrylic acid) (PAA), PEI and montmorillonite (MMT)
      clay is only 24 nm thick when deposited with 1 min exposure to each ingredient.
      Reducing the exposure time of polyelectrolytes to 5 s not only increases this
      film thickness to 55 nm but also reduces the oxygen transmission rate (OTR) to
      0.05 cm3/(m2 day atm), which is 2 orders of magnitude lower than the same film
      made using 1 min exposures. A conceptual model is proposed to explain the
      differences in growth and barrier, which are linked to polyelectrolyte
      relaxation, desorption, and interdiffusion. The universality of these findings is
      further exemplified by depositing clays with varying aspect ratios. This ability
      to quickly deposit high-barrier nanocomposite thin films opens up a tremendous
      opportunity in terms of commercial-scale processing of LbL assemblies.

PMID- 24281554
TI  - Poly(ethylene glycol)-Lipid-Conjugated Antibodies Enhance Dendritic Cell
      Phagocytosis of Apoptotic Cancer Cells.
AB  - A simple method for attaching immunoglobulin G (IgG) on the cell surface was
      successfully developed for enhancing phagocytosis of apoptotic tumor cells (ATCs)
      by dendritic cells (DCs) ex vivo. By conjugating with a poly(ethylene glycol)
      (PEG)-lipid, named the biocompatible anchor for the membrane (BAM), arbitrary IgG
      could be incorporated into the cell membrane. In particular, when IgG-BAM
      conjugates were prepared at the optimal molar ratio of IgG to BAM (1 to 20),
      almost all cells were efficiently modified with IgG by treatment with IgG-BAM.
      This simple method was successfully applied to four types of mammalian cells.
      Furthermore, treatment of ATCs with the IgG-BAM conjugate increased the
      phagocytosis ratio of ATCs by DCs two-fold when compared to no treatment. This
      phagocytosis-enhancing effect was nearly identical to treatment with a tumor
      specific IgG. Thus, without employing the tumor-specific IgG, which is difficult
      to obtain for any tumor cells and is expensive, the present method could opsonize
      ATC with the use of arbitrary IgG. The results strongly indicate that IgG-BAM
      treatment represents a promising method for opsonizing ATC with human serum IgG,
      and that this approach will lead to objective clinical responses in DC vaccines. 

PMID- 24281556
TI  - The Signalling Role of the avbeta5-Integrin Can Impact the Efficacy of AAV in
      Retinal Gene Therapy.
AB  - Sub-retinal injection of the common AAV2 pseudotypes frequently results in strong
      transduction of the retinal pigment epithelium (RPE) as well as the retina
      itself. This has been of benefit to date in human clinical trials using AAV,
      where the disease target is in the RPE. However, many mutations predisposing to
      retinal disease are located in the photoreceptor cells, present in the neural
      retina and not the RPE; in this case the sub-retinal injection route may cause an
      effective "loss" of therapeutic AAV to the RPE. The avbeta5 integrin receptor is
      highly expressed on the apical surface of the RPE, and is essential to the daily
      phagocytosis of the outer segment tips of photoreceptor cells. The transduction
      efficiency of AAV was tested in the retinas of beta5-/- mice lacking this
      receptor and showing defects in photoreceptor outer segment phagocytosis.
      Following sub-retinal injection of AAV2/5-eGFP, fluorescence was found to be
      stronger and more widespread in the neural retina of beta5-/- mice compared to
      wild-types with greatly reduced fluorescence in the RPE. Increased levels of the
      phagocytic signalling protein MFG-E8, the ligand for the avbeta5 integrin
      receptor, is found to have a moderate inhibitory effect on AAV transduction of
      the retina. However the opposite effect is found when only the integrin-binding
      domain of MFG-E8, the RGD (Arginine-Glycine-Aspartic acid) domain, was increased.
      In this case RGD enhanced AAV-mediated retinal transduction relative to RPE
      transduction. These results are presented for their relevance for the design of
      AAV-based retinal gene therapy strategies strategies targeting
      retinal/photoreceptor cells. 

PMID- 24281557
TI  - Synthesis and Spectroscopic Analysis of Novel 1H-Benzo[d]imidazoles Phenyl
      Sulfonylpiperazines.
AB  - A group of benzimidazole analogs of sildenafil, 3-benzimidazolyl-4-methoxy
      phenylsulfonylpiperazines 2-4 and 3-benzimidazolyl-4-methoxy-N,N-dimethyl-
      benzenesulfonamide (5), were efficiently synthesized. Compounds 2-5 were
      characterized by NMR and MS and contrary to the reported mass spectra of
      sildenafil, the spectra of the piperazine-containing compounds 2-4 showed a novel
      fragmentation pattern leading to an m/z = 316. A mechanism for the formation of
      this fragment was proposed. 

PMID- 24281558
TI  - Newer anticoagulants for non-valvular atrial fibrillation.
AB  - Non-valvular atrial fibrillation is a recognized risk factor for stroke and
      systemic embolism. It has been clearly established that warfarin reduces the risk
      of stroke and systemic embolism in persons with atrial fibrillation and
      additional risk factors for stroke. The use of warfarin, however, requires
      frequent monitoring, and there is great variability in patient response to
      warfarin. Warfarin interacts with several medications and foods. In addition,
      warfarin use portends a significant risk of bleeding. For these reasons, warfarin
      is frequently not prescribed to persons for whom the drug would provide a clear
      benefit. Over the past decade, attempts have been made to develop drugs that are
      at least as safe and effective as warfarin for the treatment of atrial
      fibrillation that do not require monitoring nor have as many interactions.
      Initial studies of compounds in this regard ultimately failed due to safety
      concerns, but over the past two years two novel agents have been approved by the
      United States Food and Drug Association for anticoagulation in non-valvular
      atrial fibrillation, another drug is under review, and additional compounds are
      being studied. This article will review the use of warfarin and these new agents
      in the treatment of non-valvular atrial fibrillation. 

PMID- 24281555
TI  - Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on
      Somatostatin Receptors.
AB  - G-protein coupled receptors (GPCRs) are cell surface proteins responsible for
      translating >80% of extracellular reception to intracellular signals. The
      extracellular information in the form of neurotransmitters, peptides, ions,
      odorants etc is converted to intracellular signals via a wide variety of effector
      molecules activating distinct downstream signaling pathways. All GPCRs share
      common structural features including an extracellular N-terminal, seven
      transmembrane domains (TMs) linked by extracellular/intracellular loops and the C
      terminal tail. Recent studies have shown that most GPCRs function as dimers (homo
      and/or heterodimers) or even higher order of oligomers. Protein-protein
      interaction among GPCRs and other receptor proteins play a critical role in the
      modulation of receptor pharmacology and functions. Although ~50% of the current
      drugs available in the market target GPCRs, still many GPCRs remain unexplored as
      potential therapeutic targets, opening immense possibility to discover the role
      of GPCRs in pathophysiological conditions. This review explores the existing
      information and future possibilities of GPCRs as tools in clinical pharmacology
      and is specifically focused for the role of somatostatin receptors (SSTRs) in
      pathophysiology of diseases and as the potential candidate for drug discovery. 

PMID- 24281559
TI  - Biochemical Traits, Survival and Biological Properties of the Probiotic
      Lactobacillus plantarum Grown in the Presence of Prebiotic Inulin and Pectin as
      Energy Source.
AB  - The viability of the probiotic strain Lactobacillus plantarum subsp. plantarum,
      after its passage through simulated gastric and pancreatic juices, was evaluated
      as function of its pre-growth in a medium containing the known prebiotics pectin
      or inulin, and was compared to glucose used as control. The presence of pectin or
      inulin did not markedly affect the growth (10.07 log10 colony forming units/mL
      and 10.28 log10 colony forming units/mL for pectin and inulin respectively versus
      10.42 log10 colony forming units/mL obtained for glucose). Pectin and inulin, in
      contrast to glucose, induced cell stress resistance against gastrointestinal
      juices (D log101.5 and 2.4 colony forming units/mL respectively, versus D log10
      4.0 for glucose). The data were corroborated by the analysis of the protein
      pattern following stress treatments which, in the case of microbial cells grown
      with glucose, revealed a more marked protein degradation after the double passage
      through simulated gastric and intestinal juices. Inulin stimulated the production
      of the relevant healthy bio-molecule butyrate, which amount was 30% higher
      respect of growth in the presence of glucose. Inulin and pectin improved cell
      DPPH scavenging activity, and an impressive hydrophobicity (35.28% and 34.81%,
      respectively) was observed with respect to the microbial growth in presence of
      glucose (3.39%). 

PMID- 24281560
TI  - Selecting Molecular Recognition. What Can Existing Aptamers Tell Us about Their
      Inherent Recognition Capabilities and Modes of Interaction?
AB  - The use of nucleic acid derived aptamers has rapidly expanded since the
      introduction of SELEX in 1990. Nucleic acid aptamers have demonstrated their
      ability to target a broad range of molecules in ways that rival antibodies, but
      advances have been very uneven for different biochemical classes of targets, and
      clinical applications have been slow to emerge. What sets different aptamers
      apart from each other and from rivaling molecular recognition platforms,
      specifically proteins? What advantages do aptamers as a reagent class offer, and
      how do the chemical properties and selection procedures of aptamers influence
      their function? Do the building blocks of nucleic acid aptamers dictate inherent
      limitations in the nature of molecular targets, and do existing aptamers give us
      insight in how these challenges might be overcome? This review is written as an
      introduction for potential endusers of aptamer technology who are evaluating the
      advantages of aptamers as a versatile, affordable, yet highly expandable platform
      to target a broad range of biological processes or interactions. 

PMID- 24281561
TI  - Sphingosine 1-phosphate receptor 1 as a useful target for treatment of multiple
      sclerosis.
AB  - Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, is generated from
      sphingosine by sphingosine kinases and binds five known cell surface receptors.
      S1P receptor 1 (S1P1) plays an essential role in lymphocyte egress from secondary
      lymphoid organs (SLO), as evinced by the inability of lymphocytes to exit from
      the SLO in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720) is a
      first-in-class, orally active, S1P receptor modulator with a structure closely
      related to sphingosine. FTY720 was first synthesized by chemical modification of
      a natural product, myriocin. FTY720 is effectively converted to an active
      metabolite, FTY720 phosphate (FTY720-P) by sphingosine kinases. FTY720-P shows
      high affinity to 4 of the S1P receptors (S1P1, S1P3, S1P4, and S1P5). In
      particular, FTY720-P strongly induces internalization and degradation of S1P1,
      inhibits S1P responsiveness of lymphocytes in the SLO, and acts as a functional
      antagonist at lymphocytic S1P1. Consequently, FTY720 inhibits S1P1-dependent
      lymphocyte egress from the SLO to decrease circulation of lymphocytes including
      autoreactive Th17 cells and is highly effective in experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Because
      FTY720 shows a superior efficacy in relapsing remitting MS patients compared to
      intramuscular interferon-beta-1a (Avonex(r)), S1P1 is presumed to be a useful
      target for the therapy of MS. 

PMID- 24281563
TI  - A randomized controlled trial of individual cognitive therapy, group cognitive
      behaviour therapy and attentional placebo for adolescent social phobia.
AB  - BACKGROUND: Very few studies have investigated the effects of individual disorder
      specific treatment of social phobia (SP) in adolescents. The objective of this
      study was to compare the effects of individual cognitive therapy for SP, group
      cognitive behavioural therapy (CBTG) and attentional placebo (AP) among
      adolescents with a primary diagnosis of SP. METHODS: A randomized controlled
      design was used, and a total of 279 adolescents were assessed. Fifty-seven
      adolescents, between 13 and 16 years old, were allocated to individual cognitive
      therapy, CBTG or AP. The participants were assessed before treatment, at the end
      of treatment and at a 12-month follow-up using both self-report and a semi
      structured interview. RESULTS: The individual cognitive therapy showed
      significant reductions in symptoms, impairment and diagnostic criteria both at
      the end of treatment and at the 12-month follow-up. Compared with CBTG and AP,
      the individual cognitive therapy group demonstrated significantly greater effects
      on both symptom reduction and impairment. There were no significant differences
      between CBTG and AP. CONCLUSIONS: In a direct comparison between the most
      commonly used treatments for adolescent SP, we found that individual therapy was
      the most effective, yielding better effects than both CBTG and AP.

PMID- 24281562
TI  - Cannabidiol in humans-the quest for therapeutic targets.
AB  - Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is
      attracting growing attention in medicine for its anxiolytic, antipsychotic,
      antiemetic and anti-inflammatory properties. However, up to this point, a
      comprehensive literature review of the effects of CBD in humans is lacking. The
      aim of the present systematic review is to examine the randomized and crossover
      studies that administered CBD to healthy controls and to clinical patients. A
      systematic search was performed in the electronic databases PubMed and EMBASE
      using the key word "cannabidiol". Both monotherapy and combination studies (e.g.,
      CBD + ?9-THC) were included. A total of 34 studies were identified: 16 of these
      were experimental studies, conducted in healthy subjects, and 18 were conducted
      in clinical populations, including multiple sclerosis (six studies),
      schizophrenia and bipolar mania (four studies), social anxiety disorder (two
      studies), neuropathic and cancer pain (two studies), cancer anorexia (one study),
      Huntington's disease (one study), insomnia (one study), and epilepsy (one study).
      Experimental studies indicate that a high-dose of inhaled/intravenous CBD is
      required to inhibit the effects of a lower dose of ?9-THC. Moreover, some
      experimental and clinical studies suggest that oral/oromucosal CBD may prolong
      and/or intensify ?9-THC-induced effects, whereas others suggest that it may
      inhibit ?9-THC-induced effects. Finally, preliminary clinical trials suggest that
      high-dose oral CBD (150-600 mg/d) may exert a therapeutic effect for social
      anxiety disorder, insomnia and epilepsy, but also that it may cause mental
      sedation. Potential pharmacokinetic and pharmacodynamic explanations for these
      results are discussed. 

PMID- 24281564
TI  - TNF-alpha, IFN-gamma, IL-10, and IL-4 levels were elevated in a murine model of
      human sickle cell anemia maintained on a high protein/calorie diet.
AB  - Increased frequency and risk of infection is one of the well described
      complications of sickle cell anemia (SCA). Dietary supplementation in children
      with SCA and growth retardation improved growth and decreased incidence of
      infection. We investigated the impact of a high protein diet on weight gain,
      hematological profile, and immune cytokine levels in the Berkeley model of SCA,
      16 of which were randomized to either regular mouse diet with 20% of calories
      from protein (n = 8) or a test feed with 35% of calories from protein (n = 8).
      Control mice (C57BL/6, n = 16) were correspondingly randomized, and were all feed
      ad libitum for three months with actual intake estimated by subtracting the
      weight of gnaw waste from that of the feed given. Blood was collected at
      sacrifice by cardiac puncture and plasma levels of T helper cell 1 (TH1) and TH2
      associated cytokines were measured using a multiplex antibody immobilized bead
      assay. SCA mice receiving the 35% protein diet had modest improvements in weight,
      red blood cell count, and hemoglobin level, with a slight decrease in
      reticulocyte count compared with SCA mice on the regular mouse diet. Furthermore,
      they also had significantly higher plasma levels of cytokines tumor necrosis
      factor (TNF)-alpha (P = 0.02), interferon (IFN)-gamma (P = 0.01), interleukin 10
      (IL-10; P = 0.02), and IL-4 (P = 0.02) compared with those that received the 20%
      protein diet. We conclude that providing additional protein calories to
      transgenic SCA mice increased the plasma levels of acute inflammatory cytokines
      associated with immune response to infection, which might partly explain
      decreased episodes of infection observed among supplemented children with SCA. 

PMID- 24281565
TI  - Cellular and molecular mechanisms in vascular smooth muscle cells by which total
      saponin extracted from Tribulus terrestris protects against artherosclerosis.
AB  - BACKGROUND/AIMS: Total saponin extracted from Tribulus terrestris (TSETT) has
      been reported to protect against atherosclerosis. We here investigate the
      cellular and molecular mechanisms of TSETT underlying protection against
      atherosclerosis. METHODS: Cell proliferation was measured with Methyl thiazolyl
      tetrazolium (MTT); Intracellular H2O2 was measured with DCFH-DA, a fluorescent
      dye; Intracellular free Ca(2+) was measured with a confocal laser scanning
      microscopy; Genes expression was measured with gene array and real-time
      quantitative polymerase chain reaction (RT-PCR); Phosphorylation of extracellular
      signal-regulated kinase 1/2 (phospho-ERK1/2) was measured with cell-based enzyme
      linked immunosorbent assay (ELISA) and western blotting. RESULTS: TSETT
      significantly suppressed the increase in cells proliferation induced by
      angiotensin II, significantly suppressed the increase in the intracellular
      production of H2O2 induced by angiotensin II, significantly inhibited the
      increase in intracellular free Ca(2+) induced by H2O2, significantly inhibited
      the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited
      the increase in mRNA expression of c-fos, c-jun and pkc-alpha induced by
      angiotensin II. CONCLUSION: These findings provide a new insight into the
      antiatherosclerotic properties of TSETT and provide a pharmacological basis for
      the clinical application of TSETT in anti-atherosclerosis.

PMID- 24281566
TI  - Breast implant-associated anaplastic large-cell lymphoma can be a diagnostic
      challenge for pathologists.
AB  - BACKGROUND: Primary anaplastic large-cell lymphoma (ALCL) occurring in women with
      breast implants is very rare. It is usually described as tumor cells infiltrating
      the periprosthetic capsule. These are most often revealed by a periprosthetic
      recurrent isolated effusion (seroma cavity), occurring late after implantation of
      the prosthesis. ALCL is more rarely a tumor or periprosthetic capsular
      contracture. CASE: We report a 66-year-old woman, initially diagnosed by
      cytological examination of breast effusion, in whom ALCL appeared two and a half
      months after the removal of a ruptured implant. Repeated biopsies of the
      periprosthetic capsule performed in parallel showed fibrous tissue, without tumor
      proliferation. Only meticulous histological examination of the total capsulectomy
      identified tumor cells as a thin and discontinuous layer along the inner surface
      of the capsule without capsular invasion. CONCLUSION: Awareness of the
      histological pattern of this new clinical entity is important. A total
      capsulectomy with a good sampling for microscopic examination should be conducted
      for any suspicion of breast implant-associated ALCL. Cytology-histology
      correlation is essential.

PMID- 24281570
TI  - A classification system for partial and complete DIEP flap necrosis based on a
      review of 17,096 DIEP flaps in 693 articles including analysis of 152 total flap
      failures.
AB  - BACKGROUND: In a comprehensive review of 17,096 deep inferior epigastric
      perforator (DIEP) flaps in 693 articles published between the first description
      of the DIEP flap in 1989 and August of 2011, the authors found that the methods
      used to categorize partial necrosis and fat necrosis were inconsistent. As a
      result, these surgical outcomes cannot be meaningfully compared among series and
      centers. In contrast, complete flap failure is an unambiguous and universally
      reported outcome that represents only a portion of the entire spectrum of flap
      necrosis. METHODS: The authors created a database of every article with data on
      DIEP flaps by searching PubMed and Embase for the terms "DIEP," "DIEAP,"
      "epigastric AND perforator," "perforator," and "flap AND reconstruction" and
      manually reviewing the 14,480 citations the search generated. The authors then
      reviewed 693 articles with data on DIEP flaps for incidence and other clinical
      details of flap loss, partial necrosis, and fat necrosis. RESULTS: The authors
      found a broad range of definitions of partial and fat necrosis based on different
      parameters (e.g., percentage of flap lost, area of flap lost, necessity of
      reoperation) that were not directly comparable. Of 152 documented DIEP flap
      losses, 67 had reported causes: 40 percent (27 of 67) involved venous problems,
      28 percent (19 of 67) arterial, and 21 percent (14 of 67) mechanical (pedicle
      kinking, hematoma). CONCLUSIONS: At present, there is no consensus on the
      reporting of partial necrosis and flap necrosis. The authors propose a new flap
      necrosis classification system that prevents ambiguity and allows direct
      objective comparison of surgical outcomes among centers.

PMID- 24281569
TI  - Disparities associated with breast reconstruction in Japan.
AB  - BACKGROUND: With increasing rates of postmastectomy breast reconstruction, it has
      been suggested that there is an insufficient supply of services that meet patient
      demands. This study aimed to identify potential disparities in, and variables
      associated with, postmastectomy reconstruction in Japan. METHODS: Using 20,257
      Japanese breast cancer discharge data from 2010, the authors identified 1616
      breast cancer patients, with tumor-node-metastasis classification of malignant
      tumors T1~4 and N0M0, between 20 and 59 years of age. Factors influencing the use
      of immediate breast reconstruction of either autogenous tissue or tissue expander
      placement were analyzed using multinomial logistic regression comparing no
      reconstruction to either autogenous tissue or tissue expander placement. RESULTS:
      The immediate breast reconstruction rate was 11.2 percent among the study
      patients. The rate of autogenous method use was 49 percent and the rate of tissue
      expander use was 51 percent. Tissue expander placement was performed primarily in
      patients who resided in cities (OR, 2.4; 95 percent confidence interval, 1.5 to
      4.1) and was performed at city hospitals. Patients who lived in rural areas
      primarily underwent autogenous tissue reconstruction, traveled to city hospitals
      to undergo surgery (OR, 2.0; 95 percent confidence interval, 1.0 to 4.0), and had
      normal body mass index (OR, 1.9; 95 percent confidence interval, 1.1 to 3.1).
      CONCLUSIONS: The authors identified potential disparities associated with breast
      reconstruction. These disparities might be due to limited surgery methods and
      might have excluded some patients because of their age, physical, and economic
      status. Uneven distribution of plastic surgeons might have required patients to
      travel for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 24281567
TI  - Effect of caffeic acid phenethyl ester on myringosclerosis development in the
      tympanic membrane of rat.
AB  - Myringosclerosis is hyalinization and calcification of certain areas of the
      tympanic membrane, especially the fibrous lamina propria layer and appears as
      white sclerotic lesions. Ventilation tube insertion is one of the most performed
      operations in the pediatric otorhinolaryngology practice to treat chronic otitis
      media with effusion. Myringosclerosis is a very common sequela of ventilation
      tube insertion. In this experimental study, our aim was to show the
      histopathological effects of caffeic acid phenethyl ester on myringosclerosis
      development in rat tympanic membrane after myringotomy. The rats were randomly
      categorized into four experimental groups including the comparison group (n = 4),
      non-treated group (n = 7), the saline (control) group (n = 7), the caffeic acid
      phenethyl ester group (n = 7). Non-treated group did not receive any treatment
      for 15 days. Saline (2.5 mL/kg, intraperitoneal) was administered to the third
      group once a day for 15 days. Fourth group received caffeic acid phenethyl ester
      intraperitoneally once a day at a dose of 10 MUmol/kg for 15 days. Myringotomy
      was performed on the right tympanic membrane of all rats except comparison group
      using a sterile pick with the help of an operating microscope. Histopathological
      examination of myringosclerosis formation was done by a pathologist under light
      microscope. In histopathological analysis of groups, the severity of inflammation
      was milder in caffeic acid phenethyl ester group compared to non-treated and
      saline groups (p < 0.05). There was less myringosclerotic plaques in caffeic acid
      phenethyl ester group than in non-treated and saline groups (p < 0.05). TM
      thickness measurements were very close to each other in non-treated and saline
      groups. The tympanic membrane thickness of caffeic acid phenethyl ester group was
      much thinner than the other two groups (p < 0.05). Caffeic acid phenethyl ester
      decreases inflammation severity and the formation of myringosclerotic plaques.
      These two effects resulted in thinner tympanic membranes of rats which were
      treated with caffeic acid phenethyl ester. As a result, caffeic acid phenethyl
      ester has potential preventive effects on myringosclerosis development after
      myringotomy and ventilation tube insertion.

PMID- 24281571
TI  - Patient satisfaction with breasts and psychosocial, sexual, and physical well
      being after breast augmentation in male-to-female transsexuals.
AB  - BACKGROUND: Satisfaction with breasts, sexual well-being, psychosocial well
      being, and physical well-being are essential outcome factors following breast
      augmentation surgery in male-to-female transsexual patients. The aim of this
      study was to measure change in patient satisfaction with breasts and sexual,
      physical, and psychosocial well-being after breast augmentation in male-to-female
      transsexual patients. METHODS: All consecutive male-to-female transsexual
      patients who underwent breast augmentation between 2008 and 2012 were asked to
      complete the BREAST-Q Augmentation module questionnaire before surgery, at 4
      months, and later after surgery. A prospective cohort study was designed and
      postoperative scores were compared with baseline scores. Satisfaction with
      breasts and sexual, physical, and psychosocial outcomes assessment was based on
      the BREAST-Q. RESULTS: Thirty-five male-to-female transsexual patients completed
      the questionnaires. BREAST-Q subscale median scores (satisfaction with breasts,
      +59 points; sexual well-being, +34 points; and psychosocial well-being, +48
      points) improved significantly (p < 0.05) at 4 months postoperatively and later.
      No significant change was observed in physical well-being. CONCLUSIONS: In this
      prospective, noncomparative, cohort study, the current results suggest that the
      gains in breast satisfaction, psychosocial well-being, and sexual well-being
      after male-to-female transsexual patients undergo breast augmentation are
      statistically significant and clinically meaningful to the patient at 4 months
      after surgery and in the long term. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24281572
TI  - Use of the ultrasonic bone aspirator for lateral osteotomies in rhinoplasty.
AB  - There remains considerable debate over the optimal method and approach to
      performing lateral osteotomies. Current methods rely on mechanical energy for
      performance of osteotomies, which can lead to soft-tissue injury and/or
      disruption of the bony or cartilaginous framework. The authors report the novel
      use of an ultrasonic bone aspirator device for performance of lateral osteotomies
      in rhinoplasty. The authors have found this technology to be safe and effective
      in a series of five consecutive patients. The main benefits of the device include
      avoidance of soft-tissue/mucosal injury, minimal bleeding/bruising, and the
      ability to avoid mechanical force to create bony cuts, which can destabilize the
      bony and/or cartilaginous construct of the nose. Being able to minimize tissue
      trauma with its associated morbidity while maintaining efficacy makes the
      ultrasonic bone aspirator an attractive option for lateral osteotomies in
      rhinoplasty that warrants further investigation. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24281573
TI  - The double-bubble deformity: cause, prevention, and treatment.
AB  - BACKGROUND: The double-bubble deformity is a widely recognized complication of
      breast augmentation, but there have been very few articles in the peer-reviewed
      literature devoted exclusively to this topic. METHODS: Prior publications
      addressing the anatomy of the inframammary fold and its relationship to the
      double-bubble deformity are systematically reviewed. Disagreements among
      authorities regarding the precise anatomical structure of the inframammary fold
      are addressed. The cause and surgical correction of the double-bubble deformity
      are discussed in detail as they relate to the anatomy of the fold. RESULTS: The
      key to understanding the causes and correction of the double bubble lies in an
      appreciation of the anatomy of the inframammary fold. Correction of the deformity
      varies depending on whether or not patients had preexisting anatomical features
      predisposing them to development of a double bubble. CONCLUSION: A variety of
      surgical strategies, including use of a dual-plane pocket, form-stable shaped
      implants, capsulorrhaphy, pocket plane conversion, and use of acellular dermal
      matrices can play a role in prevention and treatment of the double-bubble
      deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 24281574
TI  - Discussion: the double-bubble deformity: cause, prevention, and treatment.

PMID- 24281575
TI  - True and 'choke' anastomoses between perforator angiosomes: part i. anatomical
      location.
AB  - BACKGROUND: Reports of more than two cutaneous perforator angiosome territories
      being raised successfully in distally based sural flaps are appearing in the
      literature. Previous anatomical studies have noted that cutaneous arteries,
      connected by true anastomosis without change in caliber, frequently parallel
      cutaneous nerves. METHODS: Twenty-four (48 sides) total body lead oxide cadaver
      injection studies, including seven arterial and two venous neurovascular, were
      examined, and the results were compared with clinical thermography in Part II.
      RESULTS: Long branches of cutaneous perforators, connected in a series by true
      anastomoses, paralleled at variable distances the main trunks of cutaneous nerves
      in the head, neck, torso, and upper and lower extremities. Specifically, in the
      leg, an average of 3.2 true anastomoses (range, 1 to 5) connected perforators
      that paralleled the sural nerve on the back of the calf; and 2.5 (range, 1 to 4)
      connected perforators on the medial side of the leg. These vascular freeways were
      paralleled by the short and long saphenous veins, respectively. CONCLUSIONS: True
      anastomoses frequently connect skin perforators that course in parallel with
      cutaneous nerves and veins. They provide an explanation for the long viable flaps
      noted in the leg, and it will be shown in Part II that they can be detected
      preoperatively with thermography.

PMID- 24281576
TI  - True and 'choke' anastomoses between perforator angiosomes: part II. dynamic
      thermographic identification.
AB  - BACKGROUND: Cadaveric studies have revealed that cutaneous perforators are linked
      by either reduced-caliber "choke" arteries, or by vessels without change in
      caliber, the true anastomoses. These true anastomotic vessels are often found in
      parallel with the cutaneous nerves and accompanying veins, and are associated
      both experimentally and clinically with larger areas of flap survival. The
      Doppler probe and computed tomographic angiography are already used
      preoperatively to determine perforator locations but currently cannot reveal the
      type of anastomotic connections. METHODS: Thermal images were taken in a
      previously described fashion and compared with both computed tomographic
      angiographic studies where available and with cadaveric angiographic studies
      previously performed by the authors' laboratory. RESULTS: Perforators larger than
      1 mm were accurately localized by thermography when compared with computed
      tomographic angiography. Perforator angiosome rewarming closely approximated a
      log-based line of best fit. Interperforator zones were variable in their
      rewarming and correlated with known anatomical patterns of true and choke
      anastomoses between perforator angiosomes. CONCLUSIONS: Thermography now offers a
      new modality with which to bridge the gap not only by identifying the perforator
      "hot spots" but also by the robustness of their interconnections. The pattern of
      these interconnections seen on thermographic imaging has in turn been found to
      match those seen in the authors' cadaveric studies.

PMID- 24281577
TI  - Two-stage transplantation of cell-engineered autologous auricular chondrocytes to
      regenerate chondrofat composite tissue: clinical application in regenerative
      surgery.
AB  - BACKGROUND: The authors have developed a unique multilayered culture method that
      expands to large volumes elastic chondrocytes from a small piece of human
      auricular cartilage. In this study, the authors applied the two-stage
      transplantation method for cultured auricular chondrocytes to difficult cases of
      nasal/chin reconstruction where subcutaneous tissue is thin or scarred. METHODS:
      Auricular chondrocytes were cultured and expanded to sufficiently large volumes,
      and then, in a two-stage transplantation process, injection-transplanted into a
      patient's lower abdomen, where they were regenerated into larger chondrofat
      composite tissue in 6 months and used as a material for nasal/chin
      reconstruction. The authors then performed histologic and electron microscopic
      analysis of serial cross-sections and magnetic resonance imaging analysis of the
      chondrofat composite tissue. RESULTS: The cultured auricular chondrocytes
      consistency regenerated intraabdominally to a larger, stable neocartilage, with
      adherent fat tissue within 6 months. Eighteen patients (nose, n = 14; chin, n =
      4) underwent this procedure, and the chondrofat composite tissue was stable after
      1 to 5 years' postoperative follow-up. The chondrofat composite tissue maintained
      good shape, with no major complications. Magnetic resonance imaging showed that
      the chondrofat composite tissue was regenerated and vascularized in the abdomen
      in all 18 cases (100 percent). Infection and total absorption were not seen. Only
      partial absorption was noted (5.6 percent). CONCLUSIONS: The chondrofat composite
      tissue was found to be a new innovative graft material in which neocartilage is
      regenerated to be continuous with fat tissue by means of the neoperichondrium. It
      has thereby become possible to perform the previously impossible simultaneous
      reconstruction of cartilage and fat tissue.

PMID- 24281578
TI  - Flexor tendon repair, rehabilitation, and reconstruction.
AB  - BACKGROUND: Flexor tendon injury is a common problem that plastic surgeons are
      called on to treat. Despite their common nature, they present a challenge, not
      necessarily in the surgical treatment per se but in the ability to achieve a
      "normal" finger as the end result. Because of the difficulty in attaining good
      outcomes, much continues to be studied and written about flexor tendon injury.
      METHODS: The current literature on flexor tendon repair, rehabilitation, and
      reconstruction is reviewed. RESULTS: Aspects reviewed include type of anesthesia,
      suture material and configuration, repairs in the different flexor tendon zones,
      types of tendon rehabilitation, complications of flexor tendon surgery, and
      flexor tendon reconstruction. CONCLUSION: This review provides an update on the
      current standards in the treatment of flexor tendon injury.

PMID- 24281579
TI  - Complete avulsion of brachial plexus with associated vascular trauma: feasibility
      of reconstruction using the double free muscle technique.
AB  - BACKGROUND: Vascular trauma associated with brachial plexus injury affects the
      selection of reconstructive procedures. Often, there is a paucity of appropriate
      recipient vessels with adequate blood flow for functioning free muscle transfer.
      The presence of associated vascular injuries of the subclavian or axillary artery
      is considered a contraindication to the double free muscle technique. The authors
      hypothesized that vascular repair of subclavian or axillary artery trauma might
      not be necessary for successful reconstruction using the double free muscle
      technique, provided that the recipient arteries for functioning free muscle
      transfer (e.g., thoracoacromial and thoracodorsal arteries) are found to be
      patent on preoperative angiography. METHODS: The authors investigated the pathway
      of collateral circulation and potential recipient vessels for functioning free
      muscle transfer reconstruction in 20 brachial plexus injury patients associated
      with subclavian or axillary artery trauma using multidetector-row computed
      tomographic angiography. Based on these findings, the authors restored upper
      extremity function using the double free muscle technique without surgical repair
      of the injury to the major vessel in three patients. RESULTS: The suprascapular
      artery was the major stem artery for collateral circulation, and the circumflex
      scapular and subscapular arteries were major reentry arteries. The authors
      successfully used the thoracoacromial and thoracodorsal arteries as the recipient
      vessels for functioning free muscle transfers in the double free muscle
      technique. The preliminary functional outcomes of all three cases were
      satisfactory. CONCLUSION: This study demonstrates the feasibility of double free
      muscle technique reconstruction in brachial plexus injury patients, without
      actual vascular repair for the associated subclavian or axillary artery trauma.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24281580
TI  - Innovations in prosthetic interfaces for the upper extremity.
AB  - Advancements in modern robotic technology have led to the development of highly
      sophisticated upper extremity prosthetic limbs. High-fidelity volitional control
      of these devices is dependent on the critical interface between the patient and
      the mechanical prosthesis. Recent innovations in prosthetic interfaces have
      focused on several control strategies. Targeted muscle reinnervation is currently
      the most immediately applicable prosthetic control strategy and is particularly
      indicated in proximal upper extremity amputations. Investigation into various
      brain interfaces has allowed acquisition of neuroelectric signals directly or
      indirectly from the central nervous system for prosthetic control. Peripheral
      nerve interfaces permit signal transduction from both motor and sensory nerves
      with a higher degree of selectivity. This article reviews the current
      developments in each of these interface systems and discusses the potential of
      these approaches to facilitate motor control and sensory feedback in upper
      extremity neuroprosthetic devices.

PMID- 24281581
TI  - Le Fort III distraction using rotation advancement of the midface in patients
      with cleft lip and palate.
AB  - BACKGROUND: Patients with cleft lip and palate demonstrate a spectrum of
      maxillary growth deficiencies. The purpose of this study was to review the
      authors' experience in the treatment of midface hypoplasia in nonsyndromic cleft
      lip-cleft palate patients using rotation advancement of the midface with Le Fort
      III distraction. METHODS: A retrospective chart review was conducted to include
      all patients with nonsyndromic cleft lip and/or cleft palate who underwent Le
      Fort III rotation advancement of the midface from 1999 to 2011. Along with
      standard outcome measures, Amira imaging software was used to perform surface
      analysis on the last five consecutive patients in this series. RESULTS: Forty
      three consecutive patients met inclusion criteria. Diagnoses included unilateral
      complete cleft lip and palate (n = 25) and bilateral complete cleft lip and
      palate (n = 18). Average distraction distance measured 10.1 mm at the level of
      the zygoma (range, 6 to 15 mm). Preoperative and 6-month postoperative sella,
      nasion, A point angles measured 76.3 and 81.8 degrees; whereas sella, nasion, B
      point angles measured 79.9 and 78.7 degrees, respectively. Preoperative and 6
      month postoperative overjet measured -5.4 and 3.2 mm, whereas overbite measured
      1.9 and 1.1 mm, respectively. Six patients (13 percent) developed pseudorelapse,
      with five patients going on to have subsequent Le Fort I advancement at an
      average of 7 years after distraction (range, 2 to 11 years). CONCLUSIONS: Le Fort
      III rotation advancement of the midface addresses severe midface deficiencies in
      select patients. Whereas older techniques target occlusal correction alone,
      extending osteotomies to the Le Fort III level allows occlusal correction along
      with improvements in malar and nasal projection required to achieve facial
      harmony in this group of patients. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24281583
TI  - Evolution of ethical debate on face transplantation.
AB  - BACKGROUND: Face transplantation can provide improved quality of life to severely
      disfigured individuals. The unique challenges of face transplantation prompted
      much ethical discussion even before the first clinical case. Many deemed it
      unethical, because of issues ranging from the need for potentially harmful
      immunosuppression to the potential transfer of identity. Over time, the ethical
      debate surrounding face transplantation has evolved. METHODS: In August of 2012,
      the authors performed a review of the scientific literature on the ethics of face
      transplantation, focusing on the evolution of the discussion from before to after
      the first clinical case in 2005. The authors conducted a primary search (73 peer
      reviewed publications) in PubMed using combinations of the terms "ethics" and
      "face transplantation" and "opinions," and a secondary search (37 peer-reviewed
      publications) retrieving publications cited in some of the primary search
      findings. In total, the authors reviewed 110 articles. RESULTS: A series of 15
      issues were addressed repeatedly throughout the reviewed articles. The authors
      observed an evolution of the general opinion regarding face transplantation:
      initially seen almost unanimously as an outlandish and morally objectionable
      procedure, it began to be accepted as a feasible and necessary treatment option
      for the most significant facial defects. CONCLUSION: With growing clinical
      experience globally, new ethical questions have arisen that must be addressed to
      move the field of face transplantation forward in an ethically sound manner.

PMID- 24281582
TI  - Amifostine protects vascularity and improves union in a model of irradiated
      mandibular fracture healing.
AB  - BACKGROUND: Pathologic fractures of the mandible can be devastating to cancer
      patients and are due in large part to the pernicious effects of irradiation on
      bone vascularity. The authors' aim was to ascertain whether amifostine, a
      radioprotective drug, will preserve vascularity and improve bone healing in a
      murine model of irradiated mandibular fracture repair. METHODS: Rats were
      randomized into three groups: nonirradiated fracture (n = 9),
      irradiation/fracture (n = 5), and amifostine/irradiation/fracture (n = 7).
      Animals in the irradiation groups underwent a human equivalent dose of radiation
      directed at the left hemimandible. Animals treated in the amifostine group
      received amifostine concomitantly with radiation. All animals underwent
      unilateral left mandibular osteotomy with external fixation set to a 2.1-mm
      fracture gap. Fracture healing was allowed for 40 days before perfusion with
      Microfil. Vascular radiomorphometrics were quantified with micro-computed
      tomography. RESULTS: When compared with the irradiated/fractured group,
      amifostine treatment more than doubled the rate of fracture unions to 57 percent.
      Amifostine treatment also resulted in an increase in vessel number (123 percent;
      p < 0.05) and a corresponding decrease in vessel separation (55.5 percent; p <
      0.05) there was no statistical difference in the vascularity metrics between the
      amifostine/irradiation/fracture group and the nonirradiated/fracture group.
      CONCLUSIONS: Amifostine prophylaxis during radiation maintains mandibular
      vascularity at levels observed in nonirradiated fracture specimens, corresponding
      to improved unions. These results set the stage for clinical exploration of this
      targeted therapy alone and in combination with other treatments, to mitigate the
      effects of irradiation on bone healing and fracture repair.

PMID- 24281584
TI  - Update on scar management: guidelines for treating Asian patients.
AB  - BACKGROUND: Following injury, Asian skin has a tendency towards hyper
      pigmentation and scar formation, and therefore the prevention of scarring is
      particularly important in Asian patients. Since publication of an International
      Clinical Recommendation on Scar Management in 2002, there have been numerous
      publications in the field of scar management. Advances in understanding scar
      formation have also led to the introduction of new treatments as well as a better
      understanding of established therapeutic options. METHODS: A literature search
      for abstracts, clinical trials and meta-analyses evaluating scar prevention and
      treatment was performed using PubMed and the Cochrane Database of Systematic
      Reviews. Based on this data a panel of experts formulated treatment
      recommendations for Asian patients. RESULTS: Following surgery, scar prevention
      should be initiated in all Asian patients due to the high risk of poor scars.
      There is strong evidence for the efficacy of silicone based products, and due to
      their ease of use, they can be considered first-line therapy. Silicone gel
      (versus silicone gel sheets) products have demonstrated efficacy. For patients
      who fail to respond to first-line therapy, intralesional steroid injections,
      radiation therapy, and intralesional 5-flourouracil injections have achieved
      widespread acceptance. Laser treatments have been increasingly used, although the
      evidence remains largely anecdotal without a clear consensus on optimal
      wavelength, or amount of energy. Surgical approaches have increased in
      sophistication with recognition of the impact that tension has on scar formation.
      CONCLUSION: Updated scar management recommendations will benefit practitioners
      making decisions regarding optimal, evidence-based treatment strategies for their
      patients.

PMID- 24281585
TI  - Clinical results and patient satisfaction after pectus excavatum repair using the
      MIRPE and MOVARPE technique in adults: 10-year experience.
AB  - BACKGROUND: The minimally invasive repair of pectus excavatum (MIRPE) procedure
      as a standard procedure in children is rarely described in adolescents, adults,
      or in patients with asymmetric deformities. For these challenging cases, the
      authors have adopted a semiopen approach (minor open videoendoscopically assisted
      repair of pectus excavatum, or MOVARPE) with additional skin incisions and
      osteochondrotomies. This descriptive application study was set to assess whether
      both procedures are effective and safe in adolescents and adults, to determine
      whether they have similar complication and recurrence rates, and to analyze the
      overall outcome in nonpediatric patients. METHODS: A retrospective review of 69
      patients (45 male and 24 female patients; mean age, 20.8 years) who underwent
      either technique from August of 2002 to June of 2012 was performed.
      Intraoperative and postoperative complications, clinical outcome, and patient
      satisfaction were evaluated. RESULTS: The mean patient follow-up after bar
      removal in 55 patients was 27.3 months (p = 0.624). In the MIRPE group, two bar
      dislocations, one rupture of the internal mammary artery, and one case of
      pneumonia were observed. Mild recurrence of deformity after bar removal was
      present in four cases. Satisfaction outcomes were excellent in 70 percent in the
      MOVARPE group and 55.1 percent in the MIRPE group (p = 0.0182). CONCLUSION: The
      MOVARPE technique is a hybridized, semiopen modification of the MIRPE procedure
      that seems to be advantageous, particularly in adolescents, adults, and those
      with asymmetric pectus excavatum deformities, for overcoming resistant skeletal
      rigidity with low complication rates, high patient satisfaction, and superior
      aesthetic results. CLINICAL QUESTION/ LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24281586
TI  - Detection of perforators using thermal imaging.
AB  - BACKGROUND: Perforator flaps are commonly used in reconstructive surgery and
      require accurate vascular anatomy navigation. Several imaging methods help
      surgeons, including hand-held Doppler, color Doppler ultrasound, computed
      tomography, and magnetic resonance angiography. A growing literature supports the
      efficacy of thermal imaging in identifying perforators. This study assessed the
      efficacy of thermal imaging and perforator anatomy in four body regions. METHODS:
      Twenty volunteers had their abdomen, sacrum, and both anterolateral thighs
      assessed for cutaneous perforators using thermal imaging. Key surface landmarks
      were marked with black crosshairs centered on the umbilicus, superior natal
      cleft, and traditional anterolateral thigh flap markings. All thermal imaging
      identified perforators were marked by red crosses, immediately checked with a
      hand-held Doppler device, and marked with blue circles if not confirmed. A color
      digital photograph taken of each region was analyzed. RESULTS: Thermal imaging
      identified a total of 757 "hotspots," of which 732 (97.0 percent) were confirmed
      by hand-held Doppler. In 40 anterolateral thighs, the mean number of perforators
      identified was 1.3 within 2.5 cm and 4.6 within 5 cm of traditional landmarks. In
      the abdomen, the mean number of perforators was 0.7 and 3.7 within 2.5 cm and 5
      cm of the umbilicus, respectively. In the sacral region, there was a mean number
      of 0.3 and 2.3 perforators within 2.5 cm and 5 cm, respectively, of the superior
      natal cleft. CONCLUSIONS: Thermal imaging is a quick, easy method of assessing
      cutaneous perforators. It should be considered a useful adjunct, and further
      investigated, to determine its best role among the established perforator imaging
      methods. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

PMID- 24281587
TI  - Discussion: comparison of indocyanine green lymphographic findings with the
      conditions of collecting lymphatic vessels of limbs in patients with lymphedema.

PMID- 24281588
TI  - Why we are here: early reflections on the role of reconstructive plastic surgery
      in the 2013 Boston marathon bombings.
AB  - The 2013 Boston Marathon bombings resulted in a large and unexpected influx of
      patients requiring acute multidisciplinary surgical care. The authors describe
      the surgical management experience of these patients at Brigham & Women's
      Hospital and Brigham & Women's Faulkner Hospital, with a particular focus on the
      important role played by reconstructive plastic surgery. The authors suggest that
      this experience illustrates the value of reconstructive plastic surgery in the
      treatment of these patients specifically and of trauma patients in general, and
      argue for the increasing importance of promoting our identity as a specialty.

PMID- 24281589
TI  - Evidence-based medicine: facial skin malignancy.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify common precancerous and malignant cutaneous growths of the head
      and neck. 2. Recommend surgical treatment, including margins, based on consensus
      guidelines. 3. Counsel patients as to available evidence for expected recurrence,
      follow-up, and morbidity. SUMMARY: Skin lesion excision is the most common
      procedure performed by plastic surgeons. Because of the cumulative risk factors
      of sun and carcinogen exposure, the head and neck are the most frequently
      affected regions of the body. Timely diagnosis and treatment are critical for
      preventing continued spread and metastasis, and it is incumbent on the treating
      physician to make the appropriate recommendations for surgical margin and the
      possibility of adjuvant therapy to prevent recurrence and optimize long-term
      survival. As clinical guidelines are developed from ongoing outcome studies, new
      generations of treatment recommendations are continuously in development.
      Therefore, a systematic review of the most relevant guidelines and clinically
      rigorous studies was performed with a summarization of treatment recommendations
      for the following: actinic keratosis, Bowen disease (squamous cell in situ),
      basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and Merkel
      cell carcinoma of the head and neck.

PMID- 24281590
TI  - Evidence-based medicine: cleft palate.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe recent changes in treatment of cleft palate. 2. Compare the
      efficacy of different surgical treatments. 3. Assess their own knowledge of cleft
      palate repair. 4. Determine where further individual in-depth study and
      development are warranted. SUMMARY: The Maintenance of Certification in Plastic
      Surgery series is designed to ensure professional development and measure
      continued competency within a specialty or subspecialty. The present article
      provides an evaluation of the interval studies regarding the management of cleft
      palate with a specific focus on craniofacial growth, speech outcomes, and
      obstructive sleep apnea since the last Maintenance of Certification in Plastic
      Surgery article on the subject published in 2010. This purpose of this article is
      to update plastic and craniomaxillofacial surgeons on recent changes in treatment
      of cleft palate, provide a means for accurate self-assessment, and guide further
      individual in-depth study and development.

PMID- 24281591
TI  - Evidence-based medicine: zygoma fractures.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the anatomy of the zygoma and the common signs and symptoms of
      fracture. 2. Describe the different operative approaches for zygomatic fractures
      and understand the essentials of proper reduction and fixation. 3. Avoid and
      manage common complications associated with zygomatic fracture repair. SUMMARY:
      Methods for the evaluation and management of patients with zygomatic fractures
      continue to evolve. It is the purpose of this Maintenance of Certification
      article to provide updated recommendations for preoperative assessment, surgical
      care, and postoperative management of patients with zygomatic fractures.

PMID- 24281592
TI  - Evidence-based medicine: breast reconstruction.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Differentiate among the various techniques available to reconstructive
      breast surgeons. 2. Perform a comprehensive assessment of the breast
      reconstruction candidate. 3. Gain knowledge about the indications and
      contraindications for different breast reconstructive procedures. 4. Understand
      the complications inherent in different reconstructive breast procedures. 5.
      Summarize the long-term objective and subjective implications of surgery.
      SUMMARY: This article was prepared to accompany practice-based assessment with
      ongoing surgical education for the Maintenance of Certification for the American
      Board of Plastic Surgery. It is structured to outline the care of the patient
      with the postmastectomy breast deformity.

PMID- 24281593
TI  - Evidence-based medicine: reduction mammaplasty.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Accurately state the indications for breast imaging prior to breast
      reduction; 2. List the modifiable risk factors in a woman considering breast
      reduction. 3. Use perioperative antibiotics in an evidence based fashion. 4.
      Identify factors that are associated with higher rates of perioperative
      complications. 5. Describe the risks and benefits of breast infiltration with
      epinephrine. 6. Describe the pros and cons of using drains following breast
      reduction. 7. Describe the incidence of invasive breast cancer in surgical
      specimens compared to autopsy specimens. 8. Identify common questionnaires that
      can be used to track short and long-term outcomes following breast reduction. 9.
      List at least three current practices that are now evolving and changing based on
      evidence based medicine. SUMMARY: This paper is designed to summarize key
      evidence based steps in the care of women undergoing reduction mammaplasty. In
      addition, the authors identify gaps between how plastic surgeons practice breast
      reduction and what the best evidence supports. The article was prepared to
      accompany practice-based assessment with ongoing surgical education for the
      Maintenance of Certification Program of the American Board of Plastic Surgery.

PMID- 24281594
TI  - Evidence-based medicine: augmentation mammaplasty.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Recognize the role of biofilm in breast implant surgery and possible ways
      to reduce the incidence of capsular contracture. 2. Describe the advantages and
      disadvantages of various surgical approaches including the incision placement and
      implant location. 3. List the advantages and disadvantages of implant
      characteristics including implant fill, shell surface characteristics, and
      implant shape. 4. Take steps to avoid the phenomena of double capsule and late
      seroma. SUMMARY: This article was prepared to accompany practice-based assessment
      with ongoing surgical education for the Maintenance of Certification for the
      American Board of Plastic Surgery. It is structured to outline the care of the
      patient presenting for cosmetic breast augmentation.

PMID- 24281595
TI  - Evidence-based medicine: liposuction.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Perform preoperative assessment and patient selection for liposuction
      surgeries. 2. Explain the differences among the various types of anesthesia and
      wetting solutions used in liposuction. 3. Identify the available literature about
      skin-tightening procedures. 4. Convey to patients the complication profile for
      various modalities of liposuction. 5. Recall important ASPS consensus guidelines
      when discussing liposuction. SUMMARY: The article was prepared to feature recent
      evidence-based publications pertaining to liposuction. The authors placed special
      emphasis on the most clinically relevant data. In addition, they highlighted
      current data regarding liposuction-related fields, including autologous fat
      transfer and minimally invasive skin tightening.

PMID- 24281596
TI  - Evidence-based medicine: thumb carpometacarpal arthroplasty.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Recount the epidemiology of basilar joint arthritis. 2. Understand how the
      anatomy and kinematics of this joint contribute to the development of the disease
      process. 3. Combine patient history, clinical examination, and radiographic
      findings to formulate a diagnosis and staging of the arthritis. 4. Incorporate
      conservative management into the patient treatment plan to aid in determining a
      patient's surgical candidacy. 5. Comprehend the basic principles of available
      surgical options, potential complications, and evidence pertaining to surgical
      outcome. SUMMARY: This article has been prepared to accompany practice-based
      assessment with ongoing surgical education for the Maintenance of Certification
      for the American Board of Plastic Surgery. It is structured for physicians to
      comparatively evaluate their care of a patient with arthritis of the thumb
      carpometacarpal joint.

PMID- 24281597
TI  - Evidence-based medicine: pressure sores.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Cite risk factors for pressure sore development. 2. Detail the
      pathophysiology of pressure sores. 3. List the types and classification of
      pressure sores. 4. Consider the various nonsurgical conservative wound management
      strategies. 5. Describe the appropriate surgical interventions for each pressure
      sore type. 6. Understand the causes of recurrent pressure sores and methods of
      avoiding recurrence. SUMMARY: Pressure sores are the result of unrelieved
      pressure, usually over a bony prominence. With an estimated 2.5 million pressure
      ulcers treated annually in the United States at a cost of $11 billion, pressure
      sores represent a costly and labor-intensive challenge to the health care system.
      A comprehensive team approach can address both prevention and treatment of these
      recalcitrant wounds. Consideration must be given to the patient's medical and
      socioeconomic condition, as these factors are significantly related to outcomes.
      Mechanical prophylaxis, nutritional optimization, treatment of underlying
      infection, and spasm control are essential in management. A variety of pressure
      sore patterns exist, with surgical approaches directed to maximize future
      coverage options. A comprehensive approach is detailed in this article to provide
      the reader with the range of treatment options available.

PMID- 24281598
TI  - Evidence-based medicine: lower extremity acute trauma.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the steps for evaluation of a patient with a lower extremity
      wound before initiating medical or surgical intervention. 2. Acknowledge that
      limb amputation and salvage can both be appropriate definitive treatment options.
      3. Select proper nonsurgical or surgical techniques for wound management. 4.
      Appreciate the difference in the expected outcome according to the perspective of
      the physician versus the patient. SUMMARY: Lower extremity acute trauma is a
      common occurrence. Ultimate functional outcomes are similar whether amputation or
      salvage by limb reconstruction is the treatment pathway chosen. The
      reconstructive surgeon must be knowledgeable enough to assist in making the
      correct decision for either option. Debridement is the cornerstone of management
      before embarking on definitive wound closure. Nonsurgical devices have provided a
      transition to optimize the wound, sometimes even replacing or lessening the need
      for vascularized tissues to permit this coverage. Nevertheless, flaps will always
      have a role varying according to the involved region of the lower extremity.
      Traditional muscle flaps can often today be supplemented by the use of perforator
      flaps. The latter have great versatility as pedicled flaps for all zones of the
      lower limb, in addition to being a dependable free flap alternative. Horrendous
      injuries can now be expected to be salvaged, with a reasonable aesthetic result
      possible and with minimal donor-site morbidity. Preferences by both physicians
      and patients tend to favor the course to limb salvage, but it must be appreciated
      by the caregiver that it is always the patient who has to live with the residua
      of an altered limb and lifestyle.

PMID- 24281599
TI  - Building a legacy.

PMID- 24281600
TI  - Laser therapy for prevention and treatment of pathologic excessive scars.
AB  - BACKGROUND: The management of hypertrophic scars and keloids remains a
      therapeutic challenge. Treatment regimens are currently based on clinical
      experience rather than substantiated evidence. Laser therapy is an emerging
      minimally invasive treatment that has recently gained attention. METHODS: A meta
      analysis was conducted to evaluate the effectiveness of various laser therapies.
      The pooled response rate, pooled standardized mean difference of Vancouver Scar
      Scale scores, scar height, erythema, and pliability were reported. RESULTS:
      Twenty-eight well-designed clinical trials with 919 patients were included in the
      meta-analysis. The overall response rate for laser therapy was 71 percent for
      scar prevention, 68 percent for hypertrophic scar treatment, and 72 percent for
      keloid treatment. The 585/595-nm pulsed-dye laser and 532-nm laser subgroups
      yielded the best responses among all laser systems. The pooled estimates of
      hypertrophic scar studies also showed that laser therapy reduced total Vancouver
      Scar Scale scores, scar height, and scar erythema of hypertrophic scars.
      Regression analyses of pulsed-dye laser therapy suggested that the optimal
      treatment interval is 5 to 6 weeks. In addition, the therapeutic effect of pulsed
      dye laser therapy is better on patients with lower Fitzpatrick skin type scores.
      CONCLUSIONS: This study presents the first meta-analysis to confirm the efficacy
      and safety of laser therapy in hypertrophic scar management. The level of
      evidence for laser therapy as a keloid treatment is low. Further research is
      required to determine the mechanism of action for different laser systems and to
      examine the efficacy in quantifiable parameters, such as scar erythema, scar
      texture, degrees of symptom relief, recurrence rates, and adverse effects.

PMID- 24281601
TI  - The new criteria for body dysmorphic disorder: who makes the diagnosis?

PMID- 24281605
TI  - Surgical treatment of facial soft-tissue deformities in postburn patients: a
      proposed classification based on a retrospective study.
AB  - BACKGROUND: Postburn soft-tissue defects or scars can cause disfigurement and
      functional impairment and constitute a major therapeutic challenge. In the past
      30 years, developments in reconstructive techniques have improved the treatment
      outcomes. However, these techniques are selected mainly according to the
      surgeon's preference. There is no classification for postburn facial deformities
      that might contribute to high-level evidence and optimize management. METHODS:
      The authors reviewed the clinical cases of preexpanded local flaps, perforator
      flaps, and prefabricated flaps between January of 2005 and September of 2012 in
      their unit. Deformities were categorized according to their size and location, in
      accordance with the concept of facial aesthetic units, to show the relationship
      between different deformities and the indicated surgical techniques. The findings
      were assessed to develop a classification system. RESULTS: The study included 174
      patients with facial deformities ranging from partial unit to total face defects.
      The authors classified postburn facial skin and soft-tissue deformities as
      follows: type I, single partial unit defect; type II, total unit defect or
      deformities that partially involved two adjacent units; type III, multiunit
      defects; and type IV, total/subtotal defects. The authors recommended
      reconstructive techniques for each deformity and developed a system to score
      postoperative aesthetic and functional improvements. CONCLUSIONS: The authors
      have proposed a classification and scoring system for postburn facial deformities
      that will aid in the selection of reconstructive techniques. The proposed systems
      may facilitate multicenter studies with high-level evidence and improve the
      outcomes of postburn patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      IV.

PMID- 24281606
TI  - Local use of insulin in wounds of diabetic patients: higher temperature,
      fibrosis, and angiogenesis.
AB  - BACKGROUND: Clinical trials have shown the effectiveness of systemic and local
      insulin therapy in improving wound healing. Diabetic wounds remain a challenge
      for healthcare providers. Impaired angiogenesis and reduced granulation tissue
      formation contribute to inadequate wound healing. The aim of this study was to
      investigate the effect of local insulin administration in acute and chronic
      diabetic wounds. METHODS: Eight diabetic patients presenting with full-thickness
      wounds, of different causes, were included in this study. Five wounds were due to
      necrobiosis, one to trauma, and two to postneoplasm resection. All wounds were
      treated with regular bedside treatment. In addition, half of the wound surface
      was treated with insulin and the other half did not receive insulin.
      Thermographic and biopsy specimens of the two sides were obtained on days 0 and
      14. The presence of fibrosis, change in temperature, and amount of blood were
      evaluated. RESULTS: Significant differences in the number of vessels were
      observed on the insulin-treated side (96 +/- 47) when compared with the no
      insulin side (32.88 +/- 45) (p < 0.026). The percentage of fibrosis (insulin:
      44.42 +/- 30.42 percent versus no insulin: 12.38 +/- 36.17 percent; p < 0.047)
      and the mean temperature (insulin: 1.27 +/- 1.12 degrees C versus no-insulin:
      0.13 +/- 1.22 degrees C; p < 0.001) were also significantly different between
      sides. No adverse events related to the study occurred. CONCLUSION: The use of
      local insulin improves the formation of new blood vessels, increases fibrosis,
      and correlates with increased temperature. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 24281607
TI  - Comparison of TRAM versus DIEP flap in total vaginal reconstruction after pelvic
      exenteration.
AB  - BACKGROUND: The purpose of this study was to compare the transverse rectus
      abdominis myocutaneous (TRAM) pedicled flap with a muscle and fascia-sparing flap
      based on the deep inferior epigastric perforator (DIEP) in total vaginal
      reconstruction. The authors studied the advantages and disadvantages of both
      flaps. METHODS: From January of 1986 to July of 2010, 75 patients who underwent
      pelvic exenteration for gynecologic cancer were retrospectively reviewed. Sixty
      two patients had recurrent disease and 13 had primary tumors. Forty patients
      underwent vaginal reconstruction, 21 with TRAM flaps and seven with DIEP flaps.
      Flap survival, donor-site morbidity, neovagina stenosis, flap harvest time, and
      hospital stay were registered for both groups. RESULTS: All DIEP flaps survived
      in all patients. In the TRAM group, however, three flaps were lost because of
      total necrosis and five presented partial necrosis. Mean harvest time was 63
      minutes for the DIEP flap and 105 minutes for the TRAM flap. No abdominal wall
      complications occurred in the DIEP flap group, whereas four cases of donor-site
      morbidity were registered in the TRAM group, even though mesh was used in all
      cases. During follow-up examination, all patients had normal-appearing external
      genitalia. CONCLUSIONS: The DIEP flap seems to be a promising flap for this kind
      of reconstruction and could replace the TRAM flap. The authors detected a
      decrease in donor-site abdominal morbidity when using the DIEP flap compared with
      the TRAM flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24281608
TI  - Anatomical classification of the first dorsal metatarsal artery and its clinical
      application.
AB  - BACKGROUND: Vascularized tissue transfer pedicled with the first dorsal
      metatarsal artery is commonly used in the microsurgical reconstruction of tissue
      defect. However, there are great anatomical variations of the artery. In this
      study, the authors classified the artery based on its origin (from where it
      arises), branches, and course. The significance of this classification system
      related to harvesting a first dorsal metatarsal artery-based tissue transfer is
      also discussed. METHODS: Fresh tissue dissection (n = 48) and cast specimens (n =
      30) were studied. Three-dimensional reconstruction (n = 5) was performed based on
      the computed tomography angiogram of the adult feet. Ultrasound color Doppler
      imaging was performed on 340 feet. The anatomy of first dorsal metatarsal artery
      was also studied in patients (n = 148) who had surgery on the first web space.
      RESULTS: The intramuscular type of the artery described by Gilbert was not found
      in any of the study specimens. The most common type was found in the space
      between the dorsal interosseous muscle and the first metatarsal. The authors thus
      propose a new classification system for the first dorsal metatarsal artery: the
      arises (origin), branch, and course (ABC) classification system. CONCLUSION: The
      arises (origin), branch, and course classification system can help a surgeon to
      better understand the anatomical variations of the first dorsal metatarsal artery
      and harvest vascularized tissues based on the artery.

PMID- 24281609
TI  - Primary repair of cleft lip and nasal deformity.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the relevant anatomy and embryology that contribute to the cleft
      lip and nasal deformity. 2. Differentiate among the various forms of cleft lip,
      including microform, minor form, incomplete, complete, and bilateral. 3. List the
      options for presurgical infant orthopedics. 4. Describe the techniques and the
      expected outcomes of primary cleft lip and nasal repair. SUMMARY: The authors
      describe cleft lip and its surgical management. They address the anatomy, forms,
      techniques, and outcomes of this complex and challenging deformity.

PMID- 24281610
TI  - A nationwide curriculum analysis of integrated plastic surgery training: is
      training standardized?
AB  - BACKGROUND: The integrated model of plastic surgery education, shortly to become
      the standard for all 6-year programs, has set minimal but no maximal exposure to
      plastic surgery. The authors hypothesized that the first 3 years of integrated
      training will show variability among residency programs. METHODS: Rotation
      schedules for all 42 integrated programs were analyzed for plastic surgery versus
      18 nonplastic surgery rotations for postgraduate years 1, 2, and 3 as well as
      cumulatively for the first 3 years. Rotations "strongly suggested" by the
      Residency Review Committee on Plastic Surgery and American Board of Plastic
      Surgery were also examined. RESULTS: Postgraduate years 1 through 3 spent a wide
      range of 3 to 19 months (SD +/- 4.9 months) on plastic surgery (mean, 9.1
      months). General surgery also varied dramatically, with 8 to 21 months (SD +/-
      4.0 months) of exposure (mean, 16.3 months). Surgical subspecialty rotations
      ranged substantially from 1 to 6 months (SD +/- 1.0 months). Plastic surgery
      exposure was greater in programs based within plastic surgery departments than
      within divisions (13.8 versus 8.3 months, p < 0.005). Eighteen programs (42.9
      percent) had dedicated hand surgery rotations, while seven (16.7 percent) had
      time dedicated for research. There was also wide variability in the inclusion of
      18 nonplastic surgery rotations as well as specific "strongly suggested"
      rotations. CONCLUSIONS: The plastic surgery experience in the first 3 years of
      residency training varies by a greater than 6-fold difference among integrated
      programs. This was also found in the 2.5-fold and 6-fold differences in general
      surgery and subspecialty surgery experiences. Since standardized residency
      training is an expectation by both accrediting bodies and the public, this
      variability may warrant closer attention.

PMID- 24281611
TI  - Discussion: a nationwide curriculum analysis of integrated plastic surgery
      training: is training standardized?

PMID- 24281612
TI  - Documenting immediate gratification and guaranteeing suppression of long-term
      outcomes data.

PMID- 24281613
TI  - Reply: prospective outcome study of 225 cases of breast augmentation.

PMID- 24281614
TI  - Nothing dubious or unpredictable about 24-hour recovery in breast augmentation.

PMID- 24281615
TI  - 24-hour recovery in breast augmentation: refreshing honesty and dubious notions.

PMID- 24281616
TI  - Repairing the high-riding nipple with reciprocal transposition flaps.

PMID- 24281617
TI  - Incidence of concomitant airway anomalies when using the university of
      California, Los Angeles, protocol for neonatal mandibular distraction.

PMID- 24281618
TI  - Reply: incidence of concomitant airway anomalies when using the university of
      california, los angeles, protocol for neonatal mandibular distraction.

PMID- 24281619
TI  - Harvesting the omentum for poststernotomy mediastinitis.

PMID- 24281620
TI  - Reply: transdiaphragmatic omental harvest: a simple, efficient method for sternal
      wound coverage.

PMID- 24281621
TI  - High blood pressure (hypertension) may influence the results of clinical trials
      for scar and keloid treatments.

PMID- 24281622
TI  - Local anesthetics in liposuction: considerations for new practice advisory
      guidelines to improve patient safety.

PMID- 24281623
TI  - Reply: local anesthetics in liposuction: considerations for new practice advisory
      guidelines to improve patient safety.

PMID- 24281624
TI  - Preoperative symptoms of body dysmorphic disorder determine postoperative
      satisfaction and quality of life in aesthetic rhinoplasty.

PMID- 24281625
TI  - Deferoxamine restores callus size, mineralization, and mechanical strength in
      fracture healing after radiotherapy.

PMID- 24281626
TI  - Reply: deferoxamine restores callus size, mineralization, and mechanical strength
      in fracture healing after radiotherapy.

PMID- 24281627
TI  - Mucosal perforasomes.

PMID- 24281628
TI  - An easy and applicable method for capturing high-quality rhinoplasty videos:
      handle banded camcorder.

PMID- 24281629
TI  - Rapid resolution of post-face lift ecchymoses.

PMID- 24281630
TI  - A new, simple method to describe magnetic resonance imaging of silicone breast
      implants: silicone implants reporting and data system.

PMID- 24281631
TI  - Glomus body tumor of the breast: a rare cause of isolated breast pain.

PMID- 24281632
TI  - Sympathetic innervation of glomus tumors.

PMID- 24281633
TI  - "One-per-mil" tumescent technique for hand surgery.

PMID- 24281634
TI  - The withered hand: a scene from the gospel of Mark.

PMID- 24281635
TI  - Feraheme-enhanced magnetic resonance angiography evaluation of DIEP flap
      vasculature: early consideration of a novel technique.

PMID- 24281636
TI  - The response of breast cancer cells to mesenchymal stem cells: a possible role of
      inflammation by breast implants.
AB  - BACKGROUND: Breast implants are widely used and at times might cause inflammation
      as a foreign body, followed by fibrous capsule formation around the implant. In
      cancer, the inflamed stroma is essential for preservation of the tumor.
      Mesenchymal stem cells can be recruited to sites of inflammation, and their role
      in cancer development is debated. The authors assessed the effects of
      inflammation caused by breast implants' effects on tumor. METHODS: Mesenchymal
      stem cells were isolated from the fibrous capsules of women who underwent a
      second operation after 1 year (presenting inflammation) or after 20 years (not
      presenting inflammation) since initial surgery. After characterization, cells
      were co-cultured with MCF7, a breast cancer cell line. The expression of genes
      involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition
      was investigated, followed by Western blot analyses. RESULTS: After co-culture
      with mesenchymal stem cells from the inflamed capsule, MCF7 induced a dose- and
      time-dependent increase in proliferation. Polymerase chain reaction analyses
      revealed a dysregulation of genes involved in oncogenesis, proliferation, and
      epithelial-to-mesenchymal transition. The subsequent evaluation by Western blot
      did not confirm these results, showing only a modest decrease in the expression
      of E-cadherin after co-culture with mesenchymal stem cells (both derived from
      inflamed or control capsules). CONCLUSION: These data indicate that inflammation
      caused by breast implants partially affects proliferation of MCF7 but does not
      influence key mechanisms of tumor development.

PMID- 24281637
TI  - Discussion: the response of breast cancer cells to mesenchymal stem cells: a
      possible role of inflammation by breast implants.

PMID- 24281638
TI  - Benefits of a short, practical questionnaire to measure subjective perception of
      nasal appearance after aesthetic rhinoplasty.
AB  - BACKGROUND: The authors tested a short, practically designed questionnaire to
      assess changes in subjective perception of nasal appearance in patients before
      and after aesthetic rhinoplasty. METHODS: A prospective cohort study was
      conducted in a group of 121 patients who desired aesthetic rhinoplasty and were
      operated on by one surgeon. The questionnaire contained five questions (E1-E5)
      based on a five-point Likert scale and a visual analogue scale (range, 0 to 10).
      Two questions were designed as trick questions to help the surgeon screen for
      signs of body dysmorphic disorder. RESULTS: All patients rated the appearance of
      their nose as improved after surgery. The visual analogue scale revealed a
      Gaussian curve of normal distribution (range, 0.5 to 10) around a significant
      improvement (mean, 4.36 points, p = 0.018). Also, question E1, question E2, and
      the sum of questions E1 through E5 showed a statistically significant improvement
      after surgery (p = 1.74 * 10, p = 4.29 * 10, and p = 9.23 * 10, respectively).
      The authors found a linear relationship between preoperative score on the trick
      questions and postoperative increase in visual analogue scale score. Test-retest
      reliability could be investigated in 74 of 121 patients (61 percent) and showed a
      positive correlation between postoperative (1 year after surgery) and
      repostoperative response (2 to 4 years after surgery). CONCLUSIONS: The authors
      concluded that a surgeon performing aesthetic rhinoplasty can benefit from using
      this questionnaire. It is simple, takes no more than 2 minutes to complete, and
      provides helpful subjective information regarding patients' preoperative nasal
      appearance and postoperative surgical outcome. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24281639
TI  - Hyalurostructure treatment: superior clinical outcome through a new protocol-a 4
      year comparative study of two methods for tear trough treatment.
AB  - BACKGROUND: The tear trough represents a main aesthetic characteristic of the
      aging process, which leads many patients to the wish for a safe and efficient
      rejuvenation method to fill their eye rings. The authors analyzed results and
      complication rates of two methods for hollow eye ring treatment. METHODS: The
      authors used two methods on two patient collectives. Group A was treated using
      hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) and a reinforced 25-gauge
      Pix'l+ micro cannula. The authors developed a modified method for group B that
      included a combination of cooling of the periorbital area, no local anesthesia,
      preincision displacement of malar fat 10 mm below the orbital border, and
      postintervention corticoid therapy for 48 hours. RESULTS: Protocol B was
      associated with significantly lower complication rates. The authors also analyzed
      in how smoking, age, and skin properties might affect the clinical outcome. They
      found that choice of treatment and a history of blepharoplasty were significant
      predictive factors that correlated with complications. CONCLUSIONS: Tear trough
      treatment by hyalurostructure shows satisfying and efficient results with few
      complications. The revised technique used in group B combines multiple peri
      interventional procedures including preinjection cooling of the periorbital area,
      preincision with displacement of the malar fat 10 mm below the orbital border,
      applying gentle back-and-forth movements while injecting, and oral corticosteroid
      therapy 48 hours after intervention. This technique makes hyalurostructure a
      competent and promising treatment for tear trough management. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24281640
TI  - Adipose stromal vascular fraction isolation: a head-to-head comparison of four
      commercial cell separation systems.
AB  - BACKGROUND: Supplementation of fat grafts with stromal vascular fraction cells is
      an emerging technique used to improve graft reliability. A variety of systems for
      isolating stromal vascular fraction cells are commercially available. The lack of
      performance data obtained operating the systems in a standardized environment
      prevents objective assessment of performance. This prospective, blinded study
      compared performance of four commercially available stromal vascular fraction
      isolation systems when operated in a clinical outpatient surgery environment.
      METHODS: Four different systems were compared: (1) PNC's Multi Station, (2) CHA
      Biotech Cha-Station, (3) Cytori Celution 800/CRS System, and (4) Medi-Khan's
      Lipokit with MaxStem. Identical lipoaspirate samples from five separate volunteer
      donors were used to evaluate system process time, viable cell yield, composition,
      residual enzyme, and operating costs. RESULTS: The mean processing time ranged
      from 88 to 115 minutes. The highest mean number of viable nucleated cells was
      obtained using the Celution System (2.41 * 10 cells/g) followed by the Multi
      Station (1.07 * 10 cells/g). Lipokit and Cha-Station systems yielded nearly a log
      fewer nucleated cells (0.35 * 10 cells/g and 0.05 * 10 cells/g, respectively).
      The Celution System also yielded significantly more endothelial cells, CD34/CD31
      cells, and adipose-derived stem cells (colony-forming unit-fibroblast). Residual
      enzyme levels observed with the Multi Station, Cha-Station, and Lipokit,
      respectively, averaged 5.1-, 13.0-, and 57-fold higher than that observed with
      the Celution System. CONCLUSIONS: Although all systems generated measurable
      amounts of stromal vascular fraction, significant variability exists in the
      number, identity, and safety profiles of recovered viable cells. Side-by-side
      clinical trials will be required to establish the relevance of these differences.

PMID- 24281641
TI  - Adipose-derived stem cells exhibit antioxidative and antiapoptotic properties to
      rescue ischemic acute kidney injury in rats.
AB  - BACKGROUND: Acute kidney injury is a major challenge in critical care medicine,
      with high rates of in-hospital morbidity and mortality. Stem cell therapy has
      emerged as an evolving technology that could have a substantial impact on acute
      kidney injury outcomes in the critical care environment. Therefore, the authors
      investigated the therapeutic effects of adipose-derived stem cells in ischemic
      acute kidney injury in rats. METHODS: The authors used an ischemia-reperfusion
      induced acute kidney injury rat model. The effects of rescuing acute kidney
      injury were assessed with regard to different adipose-derived stem cell numbers
      and various routes of administration compared with sham-operated and phosphate
      buffered saline-treated groups. RESULTS: Both intrarenal arterial and intravenous
      administration of adipose-derived stem cells reduced blood urea nitrogen and
      creatinine levels, and also decreased the tubular injury score 48 hours after
      ischemia-reperfusion-induced acute kidney injury in a dose-dependent manner,
      compared with the phosphate-buffered saline-treated group. In the authors' study,
      it was determined that the optimal cell number was 5 * 10. Furthermore, adipose
      derived stem cell transplantation exhibited antioxidative and antiinflammatory
      properties to reduce apoptosis and promote proliferation of renal tubular cells.
      CONCLUSIONS: An optimal number of adipose-derived stem cells administered by
      means of the intrarenal arterial or the intravenous route effectively rescued
      ischemia-reperfusion-induced acute kidney injury in rats. Antioxidative and
      antiapoptotic properties of adipose-derived stem cells to reduce tubular cell
      injury also merit recognition and further study.

PMID- 24281644
TI  - Essential hand surgery procedures for mastery by graduating plastic surgery
      residents: a survey of program directors.
AB  - BACKGROUND: This study was designed to establish the essential hand surgery
      procedures that should be mastered by graduating plastic surgery residents. This
      framework can then be used as a guideline for developing Objective Structured
      Assessment of Technical Skill to teach technical skills in hand surgery. METHODS:
      Ten expert hand surgeons were surveyed regarding the essential hand surgery
      procedures that should be mastered by graduating plastic surgery residents. The
      top 10 procedures from this survey were then used to survey all 89 Accreditation
      Council for Graduate Medical Education-approved plastic surgery program
      directors. RESULTS: There was a 69 percent response rate to the program director
      survey (n = 61). The top nine hand surgery procedures included open carpal tunnel
      release, open A1 pulley release, digital nerve repair with microscope, closed
      reduction and percutaneous pinning of metacarpal fracture, excision of dorsal or
      volar ganglion, zone II flexor tendon repair with multistrand technique, incision
      and drainage of the flexor tendon sheath for flexor tenosynovitis, flexor tendon
      sheath steroid injection, and open cubital tunnel release. CONCLUSIONS: Surgical
      educators need to develop objective methods to teach and document technical
      skill. The Objective Structured Assessment of Technical Skill is a valid method
      for accomplishing this task. There has been no consensus regarding which hand
      surgery procedures should be mastered by graduating plastic surgery residents.
      The authors have identified nine procedures that are overwhelmingly supported by
      plastic surgery program directors. These nine procedures can be used as a
      guideline for developing Objective Structured Assessment of Technical Skill to
      teach and document technical skills in hand surgery.

PMID- 24281642
TI  - Vascular smooth muscle cell optimization of vasculogenesis within naturally
      derived, biodegradable, hybrid hydrogel scaffolds.
AB  - BACKGROUND: As vascularization represents the rate-limiting step in permanent
      incorporation of hydrogel-based tissue-regeneration templates, the authors sought
      to identify the material chemistry that would optimize endothelial cell adhesion
      and invasion into custom hydrogel constructs. The authors further investigated
      induction of endothelial tubule formation by growth factor supplementation and
      paracrine stimulation. METHODS: Hydrogel scaffolds consisting of combinations of
      alginate, collagen type I, and chitosan were seeded with human umbilical vein
      endothelial cells and maintained under standard conditions for 14 days. Cell
      density and invasion were then evaluated. Tubule formation was evaluated
      following basic fibroblast growth factor addition or co-culture with human aortic
      smooth muscle cells. RESULTS: Human umbilical vein endothelial cells demonstrated
      greatest cell-surface density and invasion volumes with alginate and collagen
      (10:1 weight/weight) scaffolds (p < 0.05). Supplementation with basic fibroblast
      growth factor increased surface density but neither invasion nor tubule
      formation. A significant increase in tubule content/organization was observed
      with increasing human aortic smooth muscle cell-to-human umbilical vein
      endothelial cell ratio co-culture. CONCLUSIONS: Alginate and collagen 10:1
      scaffolds allow for maximal cellularization compared with other combinations
      studied. Growth factor supplementation did not affect human umbilical vein
      endothelial cell invasion or morphology. Paracrine signaling by means of co
      culture with human umbilical vein endothelial cells stimulated endothelial tubule
      formation and vascular protonetwork organization. These findings serve to guide
      future endeavors toward fabrication of prevascularized tissue constructs.

PMID- 24281643
TI  - Dupuytren disease: European hand surgeons, hand therapists, and physical medicine
      and rehabilitation physicians agree on a multidisciplinary treatment guideline:
      results from the HANDGUIDE study.
AB  - BACKGROUND: Multidisciplinary treatment guidelines for Dupuytren disease can aid
      in optimizing the quality of care for patients with this disorder. Therefore,
      this study aimed to achieve consensus on a multidisciplinary treatment guideline
      for Dupuytren disease. METHODS: A European Delphi consensus strategy was
      initiated. A systematic review reporting on the effectiveness of interventions
      was conducted and used as an evidence-based starting point for this study. In
      total, 39 experts (hand surgeons, hand therapists, and physical medicine and
      rehabilitation physicians) participated in the Delphi consensus strategy. Each
      Delphi round consisted of a questionnaire, an analysis, and a feedback report.
      RESULTS: After four Delphi rounds, consensus was achieved on the description,
      symptoms, and diagnosis of Dupuytren disease. No nonsurgical interventions were
      included in the guideline. Needle and open fasciotomy, and a limited fasciectomy
      and dermofasciectomy, were seen as suitable surgical techniques for Dupuytren
      disease. Factors relevant for choosing one of these surgical techniques were
      identified and divided into patient-related (age, comorbidity), disease-related
      (palpable cord, previous surgery in the same area, skin involvement, time of
      recovery, recurrences), and surgeon-related (years of experience) factors.
      Associations of these factors with the choice of a specific surgical technique
      were reported in the guideline. Postsurgical rehabilitation should always include
      instructions and exercise therapy; postsurgical splinting should be performed on
      indication. Relevant details for the use of surgical and postsurgical
      interventions were described. CONCLUSION: This treatment guideline is likely to
      promote further discussion on related clinical and scientific issues and may
      therefore contribute to better treatment of patients with Dupuytren disease.

PMID- 24281645
TI  - Distal nerve transfers are effective in treating patients with upper trunk
      obstetrical brachial plexus injuries: an early experience.
AB  - BACKGROUND: Current surgical management of obstetrical brachial plexus injury is
      primary reconstruction with sural nerve grafts. Recently, the nerve-to-nerve
      transfer technique has been used to treat brachial plexus injury in adults,
      affording the benefit of distal coaptations that minimize regenerative distance.
      The purpose of this study was to test the hypothesis that nerve transfers are
      effective in reconstructing isolated upper trunk obstetrical brachial plexus
      injuries. METHODS: Ten patients aged 10 to 18 months were treated with three
      nerve transfers: spinal accessory nerve to the suprascapular nerve for shoulder
      abduction and external rotation; a radial to axillary nerve for shoulder
      abduction; and ulnar or median nerve transfer to the musculocutaneous nerve for
      elbow flexion. Patients were assessed preoperatively and postoperatively using
      the Active Movement Scale. All patients were followed regularly for up to 2
      years. RESULTS: Improvement in elbow and shoulder function was observed between 6
      and 24 months. By 6 months, all patients passed the cookie test. At 24 months,
      shoulder abduction improved from 3.7 +/- 0.6 to 5.0 +/- 0.5, shoulder external
      rotation from 1.8 +/- 0.4 to 4.3 +/- 0.6, shoulder flexion from 3.7 +/- 0.5 to
      5.4 +/- 0.5, elbow flexion from 3.7 +/- 0.6 to 6.3 +/- 0.2, and forearm
      supination from 2.1 +/- 0.4 to 5.9 +/- 0.2. There was no clinically appreciable
      donor-site morbidity. CONCLUSIONS: Nerve transfers reduced operative times
      compared with traditional nerve grafting procedures. Those patients showed
      significant gains in Active Movement Scale score by 24 months postoperatively,
      comparable to results achieved by nerve grafting. These findings support nerve
      transfers as a potential alternative treatment option for upper trunk obstetrical
      brachial plexus injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24281646
TI  - Foramen magnum size and involvement of its intraoccipital synchondroses in
      Crouzon syndrome.
AB  - BACKGROUND: Cranial sutures and synchondroses tend to close prematurely in
      patients with Crouzon syndrome. This influences their skull vault and skull base
      development and may involve in common disturbances such as increased intracranial
      pressure and cerebellar tonsillar herniation. The authors' hypothesis was that
      Crouzon patients patients have a smaller foramen magnum than controls because of
      premature fusion of the intraoccipital synchondroses, putting them at risk for
      cerebellar tonsillar herniation. Therefore, foramen magnum size and time of
      intraoccipital synchondroses closure were evaluated and were related to the
      presence and degree of cerebellar tonsillar herniation. METHODS: The foramen
      magnum surface area and anteroposterior diameter were measured on three
      dimensional computed tomographic scans of 27 Crouzon patients and 27 age-matched
      controls. Scans had a slice-thickness between 0.75 and 1.25 mm and were aligned
      in a three-dimensional reformatting platform. The t test was used to study size
      differences. Synchondroses were graded as described by Madeline and Elster and
      studied with ordinal logistic regression analysis. RESULTS: Crouzon patients had
      a smaller foramen magnum surface area (602 mm versus 767 mm, p < 0.001) and
      anteroposterior diameter (31 mm versus 35 mm, p < 0.001) compared with controls.
      Differences stayed constant over time. Intraoccipital synchondroses closed 3 to 9
      months earlier in Crouzon patients than in controls (p < 0.05). CONCLUSIONS:
      Since intraoccipital synchondroses close earlier in Crouzon patients, from early
      life on their foramen magnum is smaller compared with controls. Within Crouzon
      patients, the presence of cerebellar tonsillar herniation could not be related to
      foramen magnum size. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 24281647
TI  - Multifunctional gold coated thermo-sensitive liposomes for multimodal imaging and
      photo-thermal therapy of breast cancer cells.
AB  - Plasmon resonant gold nanoparticles of various sizes and shapes have been
      extensively researched for their applications in imaging, drug delivery and
      photothermal therapy (PTT). However, their ability to degrade after performing
      the required function is essential for their application in healthcare. When
      combined with biodegradable liposomes, they appear to have better degradation
      capabilities. They degrade into smaller particles of around 5 nm that are
      eligible candidates for renal clearance. Distearoyl phosphatidyl choline :
      cholesterol (DSPC : CHOL, 8 : 2 wt%) liposomes have been synthesized and coated
      with gold by in situ reduction of chloro-auric acid. These particles of size 150
      200 nm are analyzed for their stability, degradation capacity, model drug-release
      profile, biocompatibility and photothermal effects on cancer cells. It is
      observed that when these particles are subjected to low power continuous wave
      near infra-red (NIR) laser for more than 10 min, they degrade into small gold
      nanoparticles of size 5 nm. Also, the gold coated liposomes appear to have
      excellent biocompatibility and high efficiency to kill cancer cells through
      photothermal transduction. These novel materials are also useful in imaging using
      specific NIR dyes, thus exhibiting multifunctional properties for theranostics of
      cancer. 

PMID- 24281648
TI  - Probiotics for preterm neonates: what will it take to change clinical practice?
AB  - Necrotizing enterocolitis (NEC) is a major cause of mortality (25%) and morbidity
      including recurrent sepsis, dependence on parenteral nutrition, need for surgery,
      and survival with short bowel syndrome in preterm very low birth weight infants.
      Mortality (45-100%) and morbidity including the risk of long-term
      neurodevelopmental impairment are higher in extremely preterm infants needing
      surgery for NEC. Systematic reviews of randomized controlled trials (RCT)
      indicate that probiotics significantly reduce the risk of NEC (RR 0.39; 95% CI
      0.29-0.52; p < 0.00001) and all-cause mortality (RR 0.52; 95% CI 0.40-0.69; p <
      0.00001) while facilitating enteral feeds in preterm infants. At present, data
      from 25 RCT (~5,000 neonates) and reports on routine use (~3,000 neonates)
      indicates that significant adverse effects of probiotics are rare. Despite the
      robust evidence, there is still reluctance in incorporating routine probiotic
      prophylaxis in clinical practice. If the goal is to have zero tolerance for NEC,
      then probiotic prophylaxis must be adopted as soon as possible. Current gaps in
      knowledge can be addressed by continued research while providing routine
      probiotic supplementation. We believe that the concept of evidence-based practice
      of medicine has been stretched too far in this case. Trial sequential analysis
      has already shown that the evidence for probiotic supplementation was conclusive
      after 10 trials. Results of the ongoing trials are unlikely to change the
      conclusions of the systematic reviews significantly. Currently we are at trial
      number 25; how many more trials do we need? What will it take to change clinical
      practice?

PMID- 24281649
TI  - Interplay between molecule-molecule and molecule-substrate interactions: first
      principles study of fluoroform aggregates on a hexagonal ice (0001) surface.
AB  - The adsorption of fluoroform molecules on a hexagonal ice (0001) surface was
      studied using static density functional theory (DFT) calculations and Car
      Parrinello molecular dynamics (CP-MD) simulations. Extending our previous work on
      isolated molecules we focus in the present study on the interplay between
      molecule-molecule and molecule-substrate interactions. Coverages of up to a full
      monolayer were modeled by introducing two, three and four fluoroform molecules
      per unit cell of the ice (0001) substrate. Lowest-energy structures of fluoroform
      aggregates on the ice surface were determined in a systematic search by
      performing geometry optimizations from a large set of initial configurations
      chosen by chemical intuition and from snapshots taken from CP-MD simulations. In
      the vibrational analysis of the optimized geometries both conventional red- and
      unusual blue-shifting hydrogen bonds were found. The finite temperature stability
      of the lowest-energy configurations was probed by CP-MD simulations and
      conformational changes were analyzed in terms of transformations between the
      global and local minima structures. 

PMID- 24281651
TI  - Spectroscopic readout of polyoxometalates' molecular information via self
      assembly.
AB  - Polyoxometalates [SiM12O40](4-) (M = Mo(VI), W(VI)) and hemicyanine-derived
      chiral amphiphiles self-assemble in organic media where intermolecular
      interactions between POMs and hemicyanine units differ depending on the
      constituent metal ion species: this information is amplified to distinct spectral
      and self-assembling characteristics. 

PMID- 24281650
TI  - Levels of 4-1BB transcripts and soluble 4-1BB protein are elevated in the adipose
      tissue of human obese subjects and are associated with inflammatory and metabolic
      parameters.
AB  - BACKGROUND: 4-1BB, a member of the TNF receptor superfamily, has a role in
      various inflammatory pathologies through its interaction with 4-1BB ligand. We
      previously demonstrated that it participates in initiating and promoting obesity
      induced adipose inflammation in a rodent model. OBJECTIVE: In this study, we
      examined whether 4-1BB is related to obesity-induced adipose inflammation and
      metabolic parameters in humans. METHODS: A total of 50 subjects, 25 obese (body
      mass index (BMI)>=25 kg m(-2)) and 25 lean (BMI<23 kg m(-2)) participated in the
      study. The levels of 4-1BB transcripts and soluble 4-1BB protein (s4-1BB) in
      subcutaneous adipose tissue were measured by quantitative real-time PCR and
      enzyme-linked immunosorbent assay, respectively. Inflammatory and metabolic
      parameters were measured by enzymatic analysis and immunoassay. RESULTS: Obese
      subjects had higher levels of both 4-1BB transcripts and s4-1BB protein in
      subcutaneous adipose tissue than lean controls, and the levels were correlated
      with BMI and the expression of inflammatory markers, as well as with serum
      metabolic parameters. Moreover, s4-1BB was released from human adipocytes, and
      elicited chemotactic responses from human monocytes/T cells as well as enhancing
      their inflammatory activity, indicating that it may promote human adipose
      inflammation. DISCUSSION: Our data demonstrate that elevated levels of 4-1BB
      transcripts and s4-1BB in adipose tissue are closely associated with obesity
      induced inflammation and metabolic dysregulation. They suggest that both 4-1BB
      transcripts and s4-1BB could serve as novel biomarkers and/or therapeutic targets
      for obesity-induced inflammation and metabolic syndrome in humans.

PMID- 24281652
TI  - Clinical manifestations and spinal cord magnetic resonance imaging findings in
      Chinese neuromyelitis optica patients.
AB  - Neuromyelitis optica (NMO) is a disease distinct from multiple sclerosis in terms
      of clinical and magnetic resonance imaging (MRI) manifestations. Antibody to
      aquaporin-4 (AQP4) has been identified as a specific biomarker and part of the
      diagnostic criteria for NMO. Although it is relatively common in Asia, a
      comprehensive clinical and imaging evaluation of NMO has not been reported in
      Chinese patients. Here, we reviewed data from 57 Chinese cases. The patients had
      an obvious female preponderance (female/male = 8.5:1), and transverse myelitis
      (82.5%) and optic neuritis (56.1%) were the most common manifestations. In MRI,
      longitudinally extensive transverse myelitis (6.9 +/- 2.3 segments) dominated the
      spinal cord lesions, which were mainly (69.7%) distributed in cervical and
      thoracic cord. However, the length of the lesions was not correlated with onset
      age, paralysis severity, relapse rate, or duration. Among 29 patients who
      underwent AQP4 antibody assay, 17 (58.6%) were positive. There was no difference
      between seropositive and seronegative patients in terms of female preponderance,
      onset age, relapse rate, and Expanded Disability Status Scale score. However,
      seropositive patients had significantly more damaged segments (8.3 +/- 3.5) than
      did seronegative patients (4.5 +/- 1.6) (p < 0.001). The data revealed the
      clinical and MRI characteristics and AQP4 antibody status of NMO in Chinese
      patients and the correlations between them, which may have important implications
      for the diagnosis of the disease.

PMID- 24281653
TI  - Current and emerging robot-assisted endovascular catheterization technologies: a
      review.
AB  - Endovascular techniques have been embraced as a minimally-invasive treatment
      approach within different disciplines of interventional radiology and cardiology.
      The current practice of endovascular procedures, however, is limited by a number
      of factors including exposure to high doses of X-ray radiation, limited 3D
      imaging, and lack of contact force sensing from the endovascular tools and the
      vascular anatomy. More recently, advances in steerable catheters and development
      of master/slave robots have aimed to improve these practices by removing the
      operator from the radiation source and increasing the precision and stability of
      catheter motion with added degrees-of-freedom. Despite their increased
      application and a growing research interest in this area, many such systems have
      been designed without considering the natural manipulation skills and ergonomic
      preferences of the operators. Existing studies on tool interactions and natural
      manipulation skills of the operators are limited. In this manuscript, new
      technical developments in different aspects of robotic endovascular intervention
      including catheter instrumentation, intra-operative imaging and navigation
      techniques, as well as master/slave based robotic catheterization platforms are
      reviewed. We further address emerging trends and new research opportunities
      towards more widespread clinical acceptance of robotically assisted endovascular
      technologies. 

PMID- 24281654
TI  - Contrast agent bolus dispersion in a realistic coronary artery geometry:
      influence of outlet boundary conditions.
AB  - Myocardial blood flow (MBF) quantification using contrast-enhanced first-pass
      magnetic resonance imaging relies on the precise knowledge of the arterial input
      function (AIF). Due to vascular transport processes, however, the shape of the
      AIF may change from the left ventricle where the AIF is measured to the
      myocardium. We employed computational fluid dynamics simulations in a realistic
      model of the left circumflex artery to investigate the degree to which this
      effect corrupts MBF quantification. Different outlet boundary conditions were
      applied to examine their influence on the solution. Our results indicate that
      vascular transport processes in realistic coronary artery geometries give rise to
      non-negligible systematic errors in the MBF values. The magnitude of these errors
      differs considerably between the outlets of the 3D model. Moreover, outlet
      boundary conditions are shown to have a significant influence on the outflows at
      the outlets of the 3D model. In particular, the employed boundary conditions
      respond differently to an artificially inserted stenosis and to hyperemia
      condition. Finally, outlet boundary conditions are shown to have an influence on
      the resulting MBF value. Since MBF errors are different under rest and under
      hyperemia conditions, overestimation of myocardial perfusion reserve values may
      occur as well. 

PMID- 24281655
TI  - In vivo evaluation of Zr-based bulk metallic glass alloy intramedullary nails in
      rat femora.
AB  - Zr-based bulk metallic glasses (BMG) show high corrosion resistance in vitro and
      higher strength and lower Young's modulus than crystalline alloys with the
      similar composition. This study aimed to perform an in vivo evaluation of
      Zr65Al7.5Ni10Cu17.5 BMG. Osteotomy of the femur was done in rats and stabilized
      with intramedullary nails made of Zr65Al7.5Ni10Cu17.5 BMG, Ti-6Al-4V alloy, or
      316L stainless steel. Systemic and local effects of each type of nail were
      evaluated by measuring the levels of Cu and Ni in the blood and the surrounding
      soft tissue. Changes of the surface of each nail were examined by scanning
      electron microscopy (SEM). Healing of the osteotomy was evaluated by peripheral
      quantitative computed tomography and mechanical testing. No increase of Cu and Ni
      levels was recognized. Surface of the BMG showed no noticeable change, while Ti
      6Al-4V alloy showed Ca and P deposition and 316L stainless steel showed surface
      irregularities and pitting by SEM observation. The stress strain index, maximum
      torque, torsional stiffness, and energy absorption values were larger for the BMG
      than those for Ti-6Al-4V alloy, although there was no significant difference. The
      Zr-based BMG can promote osteotomy healing as fast as Ti-6Al-4V alloy, with the
      possible advantage of the Zr-based BMG that bone bonding is less likely, allowing
      easier nail removal compared with Ti-6Al-4V alloy. The Zr-based BMG is promising
      for the use in osteosynthetic devices that are eventually removed. 

PMID- 24281656
TI  - Simultaneous RGB emitting Au nanoclusters in chitosan nanoparticles for
      anticancer gene theranostics.
AB  - Advanced theranostic materials hold promise for targeted delivery of drugs, with
      the ability to follow the transport as well as its consequences. This should,
      ideally, be possible with minimum invasive surgery and having no or minimum
      cytotoxicity of the materials. It requires development of newer materials whose
      physical properties would allow for easy probe, which could carry the therapeutic
      molecules, which will be stable under physiological conditions, and at the same
      time would be able to permeate barriers to the target. We report the development
      of a composite consisting of highly fluorescent Au nanoclusters and the
      biopolymer chitosan, which could easily be converted into nanoparticles and would
      form a stable polyplex with suicide gene for induction of apoptosis in cervical
      cancer cells. The simultaneous red, green, and blue fluorescence from the
      nanoclusters provided convenient optical imaging and flow cytometry probes,
      without having to use additional dyes. Moreover, the colloidal nanocluster
      polymer composite could be converted into solid film and be stored with the
      retention of optical properties. The pH tunable optical properties in the medium
      were also intact in the films that quickly dissolved in water with retention of
      properties. 

PMID- 24281657
TI  - Global impact of heparin on gene expression profiles in neural cells infected by
      enterovirus 71.
AB  - OBJECTIVES: Heparan sulphate mimetics, particularly heparin (Hep), have
      previously been shown to considerably inhibit infection of enterovirus 71 (EV71)
      in Vero cells. Therefore, in this study, a genome-wide DNA microarray was
      performed to gain insight into the mechanism(s) of action of Hep against
      infection of a human neural cell line, SK-N-SH, with a clinical strain of EV71.
      METHODS: This study focused on a selection of EV71-induced genes whose expression
      profiling was exclusively affected by the antiviral activity of Hep. The
      selection procedure was performed through a statistical multi-level comparison
      with the following controls: negative control cells, compound control (cells
      treated with Hep only), virus control (cells treated with virus only) and
      treatment control (EV71-infected cells treated with Hep). RESULTS: Overall, of
      more than 30,000 genes studied, 14 well-known annotated genes were selected that
      may be targets for the antiviral activity of Hep against EV71 infection in neural
      cells. For most of these genes, Hep appeared to modulate the impact of EV71
      infection on the expression pattern of the genes. CONCLUSIONS: The findings of
      this research may provide initial assistance in new directions for studies to
      design molecular drug targets against EV71 infection.

PMID- 24281658
TI  - High performance PbS quantum dot sensitized solar cells via electric field
      assisted in situ chemical deposition on modulated TiO2 nanotube arrays.
AB  - Quantum dot sensitized solar cells (QDSSCs) are attractive photovoltaic devices
      due to their simplicity and low material requirements. However, efforts to
      realize high efficiencies in QDSSCs have often been offset by complicated
      processes and expensive or toxic materials, significantly limiting their useful
      application. In this work, we have realized for the first time, high performance
      PbS QDSSCs based on TiO2 nanotube arrays (NTAs) via an in situ chemical
      deposition method controlled by a low electric field. An efficiency, eta, of
      ~3.41% under full sun illumination has been achieved, which is 133.6% higher than
      the best result previously reported for a simple system without doping or co
      sensitizing, and comparable to systems with additional chemicals. Furthermore, a
      high open-circuit voltage (0.64 V), short-circuit current (8.48 mA cm(-2)) and
      fill factor (0.63) have been achieved. A great increase in the quantity of the
      loaded quantum dots (QDs) in the NTAs was obtained from the in situ electric
      field assisted chemical bath deposition (EACBD) process, which was the most
      significant contributing factor with respect to the high JSC. The high VOC and FF
      have been attributed to a much shorter electron path, less structural and
      electronic defects, and lower recombination in the ordered TiO2 NTAs produced by
      oscillating anodic voltage. Besides, the optimal film thickness (~4 MUm) based on
      the NTAs was much thinner than that of the control cell based on nanoporous film
      (~30.0 MUm). This investigation can hopefully offer an effective way of realizing
      high performance QDSSCs and QD growth/installation in other nanostructures as
      well.

PMID- 24281659
TI  - Quantitative molecular networking to profile marine cyanobacterial metabolomes.
AB  - Untargeted liquid chromatography-MS (LC-MS) is used to rapidly profile crude
      natural product (NP) extracts; however, the quantity of data produced can become
      difficult to manage. Molecular networking based on MS/MS data visualizes these
      complex data sets to aid their initial interpretation. Here, we developed an
      additional visualization step for the molecular networking workflow to provide
      relative and absolute quantitation of a specific compound in an extract. The new
      visualization also facilitates combination of several metabolomes into one
      network, and so was applied to an MS/MS data set from 20 crude extracts of
      cultured marine cyanobacteria. The resultant network illustrates the high
      chemical diversity present among marine cyanobacteria. It is also a powerful tool
      for locating producers of specific metabolites. In order to dereplicate and
      identify culture-based sources of known compounds, we added MS/MS data from 60
      pure NPs and NP analogs to the 20-strain network. This dereplicated six
      metabolites directly and offered structural information on up to 30 more. Most
      notably, our visualization technique allowed us to identify and quantitatively
      compare several producers of the bioactive and biosynthetically intriguing
      lipopeptide malyngamide C. Our most prolific producer, a Panamanian strain of
      Okeania hirsuta (PAB10FEB10-01), was found to produce at least 0.024 mg of
      malyngamide C per mg biomass (2.4%, w/dw) and is now undergoing genome sequencing
      to access the corresponding biosynthetic machinery.

PMID- 24281660
TI  - Small molecule immunomodulins from cultures of the human microbiome member
      Lactobacillus plantarum.
AB  - Lactobacillus plantarum strains are noted for their presence in the human
      gastrointestinal tract and are distinguished for their immunomodulatory actions
      and therapeutic applications. Despite the uncertainty in the underlining
      molecular mechanisms, recent evidence suggests that L. plantarum secretes
      immunomodulatory agents that alter immunological signaling cascades. Elaboration
      of these metabolic products from L. plantarum strain WCFS1 was demonstrated
      previously to correlate with the mid-log-stationary transition, perhaps
      consistent with secondary metabolite expression. Here, we present the metabolomic
      shifts revealed by principal component analysis that correspond to the mid-log
      stationary transition of L. plantarum, and identify pyroglutamic (pyro)
      dipeptides within this transition as correlative with the immunomodulatory
      actions. Four of these (pyro-phenylalanine, pyro-leucine, pyro-isoleucine, pyro
      tryptophan) were characterized and the two dominant members, pyro-phenylalanine
      and pyro-tryptophan, were directly interrogated for immunomodulatory activity
      through in vivo administration using C57BL/6 mice. Administration of these
      compounds resulted in decreased production of pro-inflammatory cytokine
      interferon (IFN)-gamma, which is of noted importance in gastrointestinal immune
      homeostasis. 

PMID- 24281661
TI  - Screening and biological activities of pedopeptins, novel inhibitors of LPS
      produced by soil bacteria.
AB  - Lipopolysaccharide (LPS) is a strong endotoxin and is delivered to the cell
      surface signaling receptor, Toll-like receptor 4 and MD-2 complex, via soluble
      cluster of differentiation (CD) 14 or membranous CD14, resulting in the induction
      of the inflammatory response. To obtain new compounds that block LPS binding to
      CD14, we designed a high-throughput screening based on time-resolved
      intermolecular fluorescence resonance energy transfer. This cell-free screening
      system successfully led to the discovery of novel inhibitors of LPS-CD14
      interaction from the library of the secondary metabolites of microorganisms. We
      identified the novel compounds pedopeptin A, B and C from a culture broth of
      Pedobacter sp. SANK 72003. Pedopeptins blocked LPS binding to CD14 in vitro with
      IC50 values of 20, 11 and 47 nM, respectively, and also inhibited LPS binding to
      the cells expressing CD14, leading to the suppression of cytokine production.
      Moreover, they showed antimicrobial activities against Escherichia coli with
      minimum inhibitory concentration ranging from 2 to 4 MUg ml(-1). 

PMID- 24281663
TI  - a-Anilinoketones, Esters and Amides: A Chemical Study.
AB  - A group of a-anilinoketones, 2-aminoalcohols, a-anilinoesters and a-anilinoamides
      were successfully synthesized and characterized by NMR spectroscopy and mass
      spectrometry. The yields were, in general, moderate to good (up to 75.4%), except
      for the a-anilinoesters (16.9-35.6%). The a-halocarbonyl starting materials
      showed different chemical reactivities. a-Haloketones and a-chloroacetates
      afforded monoalkylation, while small a-chloroamides afforded dialkylation.
      Finally, NMR spectroscopy revealed interesting structural features about the 2
      aminoalcohols and diphenylamides. 

PMID- 24281664
TI  - Phytochemical Composition, Antioxidant and Xanthine Oxidase Inhibitory Activities
      of Amaranthus cruentus L. and Amaranthus hybridus L. Extracts.
AB  - This paper describes a preliminary assessment of the nutraceutical value of
      Amaranthus cruentus (A. cruentus) and Amaranthus hybridus (A. hybridus), two food
      plant species found in Burkina Faso. Hydroacetonic (HAE), methanolic (ME), and
      aqueous extracts (AE) from the aerial parts were screened for in vitro
      antioxidant and xanthine oxidase inhibitory activities. Phytochemical analyses
      revealed the presence of polyphenols, tannins, flavonoids, steroids, terpenoids,
      saponins and betalains. Hydroacetonic extracts have shown the most diversity for
      secondary metabolites. The TLC analyses of flavonoids from HAE extracts showed
      the presence of rutin and other unidentified compounds. The phenolic compound
      contents of the HAE, ME and AE extracts were determined using the Folin-Ciocalteu
      method and ranged from 7.55 to 10.18 mg Gallic acid equivalent GAE/100 mg.
      Tannins, flavonoids, and flavonols ranged from 2.83 to 10.17 mg tannic acid
      equivalent (TAE)/100 mg, 0.37 to 7.06 mg quercetin equivalent (QE) /100 mg, and
      0.09 to 1.31 mg QE/100 mg, respectively. The betacyanin contents were 40.42 and
      6.35 mg Amaranthin Equivalent/100 g aerial parts (dry weight) in A. cruentus and
      A. hybridus, respectively. Free-radical scavenging activity expressed as IC50
      (DPPH method) and iron reducing power (FRAP method) ranged from 56 to 423 ug/mL
      and from 2.26 to 2.56 mmol AAE/g, respectively. Xanthine oxidase inhibitory
      activities of extracts of A. cruentus and A. hybridus were 3.18% and 38.22%,
      respectively. The A. hybridus extract showed the best antioxidant and xanthine
      oxidase inhibition activities. The results indicated that the phytochemical
      contents of the two species justify their traditional uses as nutraceutical food
      plants. 

PMID- 24281665
TI  - Influence of maternal bifidobacteria on the development of gut bifidobacteria in
      infants.
AB  - Intestinal microbiota plays an important role in human health by influencing
      metabolic activities that result in the creation of energy and absorbable
      nutrients, a barrier to the colonization of pathogens, and stimulation of the
      immune system. The development of fecal microbiota in neonates is crucial because
      those bacteria are the first to colonize the sterile intestine of the neonates
      and, thus, have a significant effect on the host. Initial colonization is also
      relevant to the final composition of the permanent microbiota in adults.
      Bifidobacteria are predominant in the fecal microbiota of infants, and,
      therefore, they are important to an understanding of how commensal bifidobacteria
      is established in the intestine of infants. While the mother's bifidobacteria are
      considered to significantly influence the infant's bifidobacteria, it is not
      clear whether a specific bifidobacterial strain transmits vertically from mother
      to infant and what factors of the mother before delivery influence the
      establishment of intestinal bifidobacteria in infants. This review focuses on the
      impact of maternal bifidobacteria on the development of gut bifidobacteria in the
      infant and suggests that there is cumulative evidence regarding bifidobacterial
      transfer from the maternal gut or breast milk to the infant gut. 

PMID- 24281662
TI  - Gene therapy for the treatment of Parkinson's disease: the nature of the
      biologics expands the future indications.
AB  - The pharmaceutical industry's development of therapeutic medications for the
      treatment of Parkinson's disease (PD) endures, as a result of the continuing need
      for better agents, and the increased clinical demand due to the aging population.
      Each new drug offers advantages and disadvantages to patients when compared to
      other medical offerings or surgical options. Deep brain stimulation (DBS) has
      become a standard surgical remedy for the effective treatment of select patients
      with PD, for whom most drug regimens have failed or become refractory. Similar to
      DBS as a surgical option, gene therapy for the treatment of PD is evolving as a
      future option. In the four different PD gene therapy approaches that have reached
      clinical trials investigators have documented an excellent safety profile
      associated with the stereotactic delivery, viral vectors and doses utilized, and
      transgenes expressed. In this article, we review the clinically relevant gene
      therapy strategies for the treatment of PD, concentrating on the published
      preclinical and clinical results, and the likely mechanisms involved. Based on
      these presentations, we advance an analysis of how the nature of the gene therapy
      used may eventually expand the scope and utility for the management of PD. 

PMID- 24281666
TI  - Physical factors affecting plasmid DNA compaction in stearylamine-containing
      nanoemulsions intended for gene delivery.
AB  - Cationic lipids have been used in the development of non-viral gene delivery
      systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary
      amine group when in solution, is able to compact genetic material by
      electrostatic interactions. In dispersed systems such as nanoemulsions this lipid
      anchors on the oil/water interface confering a positive charge to them. The aim
      of this work was to evaluate factors that influence DNA compaction in cationic
      nanoemulsions containing stearylamine. The influence of the stearylamine
      incorporation phase (water or oil), time of complexation, and different
      incubation temperatures were studied. The complexation rate was assessed by
      electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex
      characterization was done by Dynamic Light Scattering (DLS). The results
      demonstrate that the best DNA compaction process occurs after 120 min of
      complexation, at low temperature (4 +/- 1  degrees C), and after incorporation of
      the cationic lipid into the aqueous phase. Although the zeta potential of
      lipoplexes was lower than the results found for basic nanoemulsions, the
      granulometry did not change. Moreover, it was demonstrated that lipoplexes are
      suitable vehicles for gene delivery. 

PMID- 24281667
TI  - The Potential Therapeutic Efficacy of Lactobacillus GG in Children with Food
      Allergies.
AB  - Food allergy (FA) continues to be a growing health concern for infants living in
      Western countries. The long-term prognosis for the majority of affected infants
      is good, with 80-90% naturally acquiring tolerance by the age of five years.
      However, recent studies suggest that the natural history of FA is changing, with
      an increasing persistence until later ages. The pathogenesis of FA as well as
      oral tolerance is complex and not completely known, although numerous studies
      implicate gut-associated immunity and enteric microflora, and it has been
      suggested that an altered composition of intestinal microflora results in an
      unbalanced local and systemic immune response to food allergens. In addition,
      there are qualitative and quantitative differences in the composition of gut
      microbiota between patients affected by FA and healthy infants. These findings
      prompted the concept that specific beneficial bacteria from the human intestinal
      microflora, designated probiotics, could restore intestinal homeostasis and
      prevent or alleviate allergy, at least in part by interacting with the intestinal
      immune cells. 

PMID- 24281668
TI  - Removal of cholera toxin from aqueous solution by probiotic bacteria.
AB  - Cholera remains a serious health problem, especially in developing countries
      where basic hygiene standards are not met. The symptoms of cholera are caused by
      cholera toxin, an enterotoxin, which is produced by the bacterium Vibrio
      cholerae. We have recently shown that human probiotic bacteria are capable of
      removing cyanobacterial toxins from aqueous solutions. In the present study we
      investigate the ability of the human probiotic bacteria, Lactobacillus rhamnosus
      strain GG (ATCC 53103) and Bifidobacterium longum 46 (DSM 14583), to remove
      cholera toxin from solution in vitro. Lactobacillus rhamnosus strain GG and
      Bifidobacterium longum 46 were able to remove 68% and 59% of cholera toxin from
      aqueous solutions during 18 h of incubation at 37  degrees C, respectively. The
      effect was dependent on bacterial concentration and L. rhamnosus GG was more
      effective at lower bacterial concentrations. No significant effect on cholera
      toxin concentration was observed when nonviable bacteria or bacterial supernatant
      was used. 

PMID- 24281670
TI  - Reduction of hydroxy-functionalised carbaboranyl carboxylic acids to tertiary
      alcohols by organolithium reagents.
AB  - Reduction of hydroxy-functionalised carbaboranyl carboxylic acids by
      organolithium reagents yields the corresponding tertiary alcohols. This is in
      contrast to exo-polyhedral C-C bond cleavage of unsubstituted carbaboranyl
      carboxylic acids upon reaction with lithium organyls. The proposed dimeric
      contact ion pairs may also explain the formation of tertiary alcohols instead of
      the expected ketones. 

PMID- 24281669
TI  - Voluntary wheel running does not affect lipopolysaccharide-induced depressive
      like behavior in young adult and aged mice.
AB  - OBJECTIVE(S): Peripheral stimulation of the innate immune system with
      lipopolysaccharide (LPS) causes prolonged depressive-like behavior in aged mice
      that is dependent on indoleamine 2,3 dioxygenase (IDO) activation. Regular
      moderate-intensity exercise training has been shown to exert neuroprotective
      effects that might reduce depressive-like behavior in aged mice. The purpose of
      this study was to test the hypothesis that voluntary wheel running (VWR) would
      attenuate LPS-induced depressive-like behavior and brain IDO gene expression in 4
      and 22-month-old C57BL/6J mice. METHODS: Mice were housed with a running wheel
      (VWR) or no wheel (standard) for 30 (young adult mice) or 70 days (aged mice),
      after which they were intraperitoneally injected with LPS (young adult mice: 0.83
      mg/kg; aged mice: 0.33 mg/kg). RESULTS: Young adult VWR mice ran on average 6.9
      km/day, while aged VWR mice ran on average 3.4 km/day. Both young adult and aged
      VWR mice increased their forced exercise tolerance compared to their respective
      standard control groups. VWR had no effect on LPS-induced anorexia, weight loss,
      increased immobility in the tail suspension test and decreased sucrose preference
      in either young adult or aged mice. Four (young adult mice) and 24 h (aged mice)
      after injection of LPS, mRNA transcripts for TNF-alpha, IL-1beta, IL-6, and IDO
      were upregulated in the whole brain independently of VWR. CONCLUSION: Prolonged
      physical exercise has no effect on the neuroinflammatory response to LPS and its
      behavioral consequences in young adult and aged mice.

PMID- 24281671
TI  - COPD and thyroid dysfunctions.
AB  - BACKGROUND: Chronic obstructive pulmonary (COPD) is one of the major causes of
      morbidity and mortality in the world. COPD is characterized by chronic
      inflammation in the pulmonary compartment and in the systemic circulation. This
      disorder is associated with clinically significant alterations in biochemistry
      and organ function; thyroid dysfunctions are common in chronic diseases, such as
      COPD. Several characteristics of COPD patients could increase their likelihood of
      developing hypothyroidism or hyperthyroidism. The purpose of our study was to
      assess the impact of thyroid dysfunction in patients with COPD. METHODS: We
      evaluated the pulmonary function tests, arterial blood gases, maximal inspiratory
      pressure (MIP), maximal expiratory pressure (MEP), and thyroid functions in
      patients with COPD, recruited between admissions in Respiratory Diseases Unit,
      Policlinico Umberto I, Rome, Italy, from June 2012 to May 2013. We selected
      patients with subclinical hypothyroidism (ScH), overt hypothyroidism, and
      hyperthyroidism, and a control group without thyroid disturbance. RESULTS: Our
      results indicate that patients with overt hypothyroidism have lower levels of
      pO2, MIP, and MEP compared with subjects with ScH, hyperthyroidism, and the
      control group. We also found a substantial tendency towards pCO2 levels increase
      in patients with hypothyroidism (p = 0.06). CONCLUSIONS: Patients with thyroid
      dysfunctions have a greater impairment of MIP and MEP and a negative correlation
      was observed between hypoxemia and TSH. Further studies are needed to investigate
      whether the treatment of thyroid disfunction could have a beneficial effect on
      COPD patients' lung function and prognosis.

PMID- 24281672
TI  - A crossed molecular beam and ab initio investigation of the exclusive methyl loss
      pathway in the gas phase reaction of boron monoxide (BO; X2Sigma+) with
      dimethylacetylene (CH3CCCH3; X1A(1g)).
AB  - The crossed molecular beam reaction of boron monoxide ((11)BO; X(2)Sigma(+)) with
      dimethylacetylene (CH3CCCH3; X(1)A(1g)) was investigated at a collision energy of
      23.9 +/- 1.5 kJ mol(-1). The scattering dynamics were suggested to be indirect
      (complex forming reaction) and were initiated by the addition of
      (11)BO(X(2)Sigma(+)) with the radical center located at the boron atom to the pi
      electron density at the acetylenic carbon-carbon triple bond without entrance
      barrier leading to cis-trans(11)BOC4H6 doublet radical intermediates. cis
      (11)BOC4H6 underwent cis-trans isomerization followed by unimolecular
      decomposition via a methyl group (CH3) loss forming 1-propynyl boron monoxide
      (CH3CC(11)BO) in an overall exoergic reaction (experimental: -91 +/- 22 kJ mol(
      1); theoretical: -105 +/- 9 kJ mol(-1); NIST: -104 +/- 12 kJ mol(-1)) via a tight
      exit transition state; trans-(11)BOC4H6 was found to lose a methyl group
      instantaneously. Neither atomic nor molecular hydrogen loss pathways were
      detectable. The experimental finding of an exclusive methyl loss pathway gains
      full support from our computational study predicting a methyl group versus atomic
      hydrogen loss branching ratio of 99.99% to 0.01% forming 1-propynyl boron
      monoxide (CH3CC(11)BO) and 1-methyl-propadienyl boron monoxide
      (CH3((11)BO)CCCH2), respectively.

PMID- 24281673
TI  - Improved management of winter operations to limit subsurface contamination with
      degradable deicing chemicals in cold regions.
AB  - This paper gives an overview of management considerations required for better
      control of deicing chemicals in the unsaturated zone at sites with winter
      maintenance operations in cold regions. Degradable organic deicing chemicals are
      the main focus. The importance of the heterogeneity of both the infiltration
      process, due to frozen ground and snow melt including the contact between the
      melting snow cover and the soil, and unsaturated flow is emphasised. In this
      paper, the applicability of geophysical methods for characterising soil
      heterogeneity is considered, aimed at modelling and monitoring changes in
      contamination. To deal with heterogeneity, a stochastic modelling framework may
      be appropriate, emphasizing the more robust spatial and temporal moments.
      Examples of a combination of different field techniques for measuring subsoil
      properties and monitoring contaminants and integration through transport
      modelling are provided by the SoilCAM project and previous work. Commonly, the
      results of flow and contaminant fate modelling are quite detailed and complex and
      require post-processing before communication and advising stakeholders. The
      managers' perspectives with respect to monitoring strategies and challenges still
      unresolved have been analysed with basis in experience with research
      collaboration with one of the case study sites, Oslo airport, Gardermoen, Norway.
      Both scientific challenges of monitoring subsoil contaminants in cold regions and
      the effective interaction between investigators and management are illustrated. 

PMID- 24281674
TI  - Elevated root retention of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in
      coniferous trees.
AB  - For decades, the explosive RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) has been
      used for military and industrial applications. Residues of RDX pollute soils in
      large areas globally and the persistence and high soil mobility of these residues
      can lead to leaching into groundwater. Dendroremediation, i.e. the long-term use
      of trees to clean up polluted soils, is gaining acceptance as a green and
      sustainable strategy. Although the coniferous tree species Norway spruce and
      Scots pine cover large areas of military land in Central Europe, the potential of
      any coniferous tree for dendroremediation of RDX is still unknown. In this study,
      uptake experiments with a (14)C-labelled RDX solution (30 mg L(-1)) revealed that
      RDX was predominantly retained in the roots of 6-year-old coniferous trees. Only
      23 % (pine) to 34 % (spruce) of RDX equivalents (RDXeq) taken up by the roots
      were translocated to aboveground tree compartments. This finding contrasts with
      the high aerial accumulation of RDXeq (up to 95 %) in the mass balances of all
      other plant species. Belowground retention of RDXeq is relatively stable in fine
      root fractions, since water leaching from tissue homogenates was less than 5 %.
      However, remobilisation from milled coarse roots and tree stubs reached up to 53
      %. Leaching from homogenised aerial tree material was found to reach 64 % for
      needles, 58 % for stems and twigs and 40 % for spring sprouts. Leaching of RDX by
      precipitation increases the risk for undesired re-entry into the soil. However,
      it also opens the opportunity for microbial mineralisation in the litter layer or
      in the rhizosphere of coniferous forests and offers a chance for repeated uptake
      of RDX by the tree roots.

PMID- 24281675
TI  - Photosensitised humic-like substances (HULIS) formation processes of atmospheric
      significance: a review.
AB  - Photosensitised reactions can produce compounds that closely resemble the humic
      like substances (HULIS) occurring in atmospheric aerosols. The relevant processes
      have been observed in the laboratory, in both gas-solid systems and the aqueous
      phase. They involve triplet sensitisers (such as benzophenones, anthraquinones
      and nitroaromatic compounds, which yield reactive triplet states after sunlight
      absorption) or photogenerated oxidants like (*)OH, in the presence of substrates
      that undergo oligomerisation reactions upon oxidation. Formation of higher
      molecular weight compounds, modification of the wettability properties of organic
      films and photoproduction of substances with humic-like fluorescence properties
      have been observed as a consequence of the photosensitised reactions. Ozone plays
      an important but still not completely clear role in gas-solid systems. 

PMID- 24281676
TI  - Spatial modeling of ecological areas by fitting the limiting factors for As in
      the vicinity of mine, Serbia.
AB  - Elevated arsenic (As) concentrations in soil are often found in the vicinity of
      certain mineral deposits that have been, or are currently, under exploitation,
      regardless of the target resource. Detailed study of such areas for safe
      agriculture requires considerable financial costs and long periods of time.
      Application of an appropriate spatial model that describes the behavior of
      arsenic in soil and plants can significantly ease the whole investigation
      process. This paper presents a model of ecological security of an area that, in
      the past, was an antimony mine and has a naturally high content of arsenic. For
      simulation and modeling the geographic information science (GIS) technology with
      the inserted predictors influencing the accessibility of As and its content in
      plants was used. The results obtained were the following: (1) a categorization of
      contaminated soils according to soil properties was developed; (2) the proposed
      methodology allows focusing on particular suspect area saving an energy and human
      resource input; and (3) new safe areas for growing crops in contaminated area
      were modeled. The application of the proposed model of As solubility to various
      crops grown around a former antimony mine near the village of Lisa, southwest
      Serbia showed that significant expansion of the areas suitable for growing
      potato, raspberry, and pasture was possible. 

PMID- 24281677
TI  - Adsorption equilibrium and dynamics of gasoline vapors onto polymeric adsorbents.
AB  - The emission of gasoline vapors is becoming a significant environmental problem
      especially for the population-dense area and also results in a significant
      economic loss. In this study, adsorption equilibrium and dynamics of gasoline
      vapors onto macroporous and hypercrosslinked polymeric resins at 308 K were
      investigated and compared with commercial activated carbon (NucharWV-A 1100). The
      results showed that the equilibrium and breakthrough adsorption capacities of
      virgin macroporous and hypercrosslinked polymeric resins were lower than virgin
      activated carbon. Compared with origin adsorbents, however, the breakthrough
      adsorption capacities of the regenerated activated carbon for gasoline vapors
      decreased by 58.5 % and 61.3 % when the initial concentration of gasoline vapors
      were 700 and 1,400 mg/L, while those of macroporous and hypercrosslinked resins
      decreased by 17.4 % and 17.5 %, and 46.5 % and 45.5 %, respectively. Due to the
      specific bimodal property in the region of micropore (0.5-2.0 nm) and meso
      macropore (30-70 nm), the regenerated hypercrosslinked polymeric resin exhibited
      the comparable breakthrough adsorption capacities with the regenerated activated
      carbon at the initial concentration of 700 mg/L, and even higher when the initial
      concentration of gasoline vapors was 1,400 mg/L. In addition, 90 % of relative
      humidity had ignorable effect on the adsorption of gasoline vapors on
      hypercrosslinked polymeric resin. Taken together, it is expected that
      hypercrosslinked polymeric adsorbent would be a promising adsorbent for the
      removal of gasoline vapors from gas streams.

PMID- 24281679
TI  - Removal of tetracycline and oxytetracycline by microscale zerovalent iron and
      formation of transformation products.
AB  - The main objective of this study was to determine the removal mechanism of
      tetracycline (TC) and oxytetracycline (OTC) by microscale zerovalent iron (mZVI)
      and the formation of transformation products during their removal studies.
      Solution pH, iron dose, and reaction temperature were studied with a batch
      experimental series in order to evaluate the removal efficiency of TC and OTC and
      the adsorption kinetics. The results showed that pH was a key factor in removing
      both tetracycline compounds, although increasing the temperature and iron dose
      enhanced their removal efficiency. The optimal pH was similarly found as 3 for
      both tetracycline and oxytetracycline. The kinetics of adsorption fitted the
      pseudo-second-order model perfectly. The adsorption data was interpreted by the
      Langmuir model with the maximum adsorption capacity of 23.98 and 34.01 mg g(-1)
      (60  degrees C) of TC and OTC on mZVI, respectively. The main transformation
      product was 4-epi-tetracycline for TC which quickly sorbed onto mZVI within 15
      min. beta-Apo-OTC and alpha-Apo-OTC were found as OTC transformation products.
      The removal mechanism of TC and OTC using mZVI surface was due to the adsorption
      rather than the degradation process.

PMID- 24281678
TI  - Pollution due to hazardous glass waste.
AB  - Pollution resulting from hazardous glass (HG) is widespread across the globe,
      both in terms of quantity and associated health risks. In waste cathode ray tube
      (CRT) and fluorescent lamp glass, mercury and lead are present as the major
      pollutants. The current review discusses the issues related to quantity and
      associated risk from the pollutant present in HG and proposes the chemical,
      biological, thermal, hybrid, and nanotechniques for its management. The hybrid is
      one of the upcoming research models involving the compatible combination of two
      or more techniques for better and efficient remediation. Thermal mercury
      desorption starts at 100  degrees C but for efficient removal, the temperature
      should be >460  degrees C. Involvement of solar energy for this purpose makes the
      research more viable and ecofriendly. Nanoparticles such as Fe, Se, Cu, Ni, Zn,
      Ag, and WS2 alone or with its formulation can immobilize heavy metals present in
      HG by involving a redox mechanism. Straight-line equation from year-wise sale can
      provide future sale data in comparison with lifespan which gives future pollutant
      approximation. Waste compact fluorescent lamps units projected for the year 2015
      is 9,300,000,000 units and can emit nearly 9,300 kg of mercury. On the other
      hand, CRT monitors have been continuously replaced by more improved versions like
      liquid crystal display and plasma display panel resulting in the production of
      more waste. Worldwide CRT production was 83,300,000 units in 2002 and can
      approximately release 83,000 metric tons of lead.

PMID- 24281680
TI  - Do GSTT1 and GSTM1 polymorphisms influence intoxication events in individuals
      occupationally exposed to pesticides?
AB  - This study evaluated the variability of GSTM1 and GSTT1 polymorphisms in
      individuals occupationally exposed to pesticides in ten Goias municipalities that
      present intense agricultural activity. We evaluated blood samples of 235
      individuals, which 120 were rural workers occupationally exposed to pesticides
      and 115 formed the control group, analyzing GST polymorphisms by quantitative
      polymerase chain reaction (qPCR).The exposed group consisted of 111 men and nine
      women only getting an average of 39 +/- 9 years. These workers were from ten
      rural municipalities situated at Goias state. It was found that 18 % of the
      exposed individuals had the GSTT1 null genotype and 49 % had the GSTM1 null
      genotype, and 10 % had both null genotypes. Data as intoxication (42 %), use of
      Personal Protection Equipment (PPE; 52 %) and if the worker prepared the
      pesticide (7 %), or if just applied the pesticide (22 %) or if the worker
      prepared and applied (71 %) have all been correlated with genetic polymorphisms.
      There were no statistically significant differences between the GSTM1 and GSTT1
      polymorphisms between control and exposed groups. Finally, we could not associate
      a null GSTT1 or null GSTM1 polymorphisms or both to intoxication events caused by
      pesticides, but instead we presented the importance to use PPE to prevent such
      harm, once we found a statistically significant association between the use of
      PPE and events of intoxication (p <= 0.001).

PMID- 24281681
TI  - Prospecting metal-resistant plant-growth promoting rhizobacteria for
      rhizoremediation of metal contaminated estuaries using Spartina densiflora.
AB  - In the salt marshes of the joint estuary of Tinto and Odiel rivers (SW Spain),
      one of the most polluted areas by heavy metals in the world, Spartina densiflora
      grows on sediments with high concentrations of heavy metals. Furthermore, this
      species has shown to be useful for phytoremediation. The total bacterial
      population of the rhizosphere of S. densiflora grown in two estuaries with
      different levels of metal contamination was analyzed by PCR denaturing gradient
      gel electrophoresis. Results suggested that soil contamination influences
      bacterial population in a greater extent than the presence of the plant. Twenty
      two different cultivable bacterial strains were isolated from the rhizosphere of
      S. densiflora grown in the Tinto river estuary. Seventy percent of the strains
      showed one or more plant growth-promoting (PGP) properties, including phosphate
      solubilization and siderophores or indolacetic acid production, besides a high
      resistance towards Cu. A bacterial consortium with PGP properties and very high
      multiresistance to heavy metals, composed by Aeromonas aquariorum SDT13,
      Pseudomonas composti SDT3, and Bacillus sp. SDT14, was selected for further
      experiments. This consortium was able to two-fold increase seed germination and
      to protect seeds against fungal contamination, suggesting that it could
      facilitate the establishment of the plant in polluted estuaries.

PMID- 24281682
TI  - Performance and bacterial communities of successive alkalinity-producing systems
      (SAPSs) in passive treatment processes treating mine drainages differing in
      acidity and metal levels.
AB  - Successive alkalinity-producing systems (SAPSs) is a key unit process in the
      passive treatment of acidic mine drainage. Physico-chemistry and pyrosequencing
      based bacterial communities of two passive treatment processes in Gapjung (GJ)
      and Seokbong (SB) were analyzed. The influent of SB harbored higher levels of
      acidity and metals than that of GJ. SAPS-SB demonstrated better performance of
      acidity neutralization and metal removal than SAPS-GJ, despite its shorter
      hydraulic retention time and higher acidity. System diagnosis revealed that the
      capacities of SAPSs were not well predicted in the design steps. Bacterial
      diversity indices and composition were compared at the same sequence read number
      for fair evaluation. Most of the bacterial sequences were affiliated with
      uncultured species. A notable difference was observed in the bacterial community
      compositions of the SAPSs in GJ and SB. Classes of putative sulfate-reducing
      bacteria, Clostridia (8.3 %) and Deltaproteobacteria (6.1 %), were detected in
      SAPS-GJ, and Clostridia (14.6 %) was detected in SAPS-SB. Bacilli, which is not a
      known sulfate-reducing bacterial group, was the second largest class (12.8 %) in
      SAPS-GJ and the largest class (51.1 %) in SAPS-SB, suggesting that Bacilli may
      have a prominent role in SAPS. One hundred ninety operational taxonomic units
      were shared, which occupied ~10 % of each number of total operational taxonomic
      units in SAPS-GJ and SAPS-SB, respectively. Bacilli and Clostridia were the major
      shared classes, and Bacillus, Lysinibacillus, and Ureibacillus were the major
      shared genera. Rarefaction analysis, richness estimates, diversity estimates, and
      abundance rank analysis show that the sediment bacterial community of SAPS-GJ was
      more diverse and more evenly distributed than that of SAPS-SB.

PMID- 24281683
TI  - Stable carbon isotope ratio in atmospheric CO2 collected by new diffusive
      devices.
AB  - In this paper, stable carbon isotope ratios (delta (13)C) were determined in the
      atmosphere by using a Ca-based sorbent, CaO/Ca12Al14O33 75:25 w/w, for passively
      collecting atmospheric CO2, in both field and laboratory experiments. Field
      measurements were conducted in three environments characterized by different
      carbon dioxide sources. In particular, the environments under consideration were
      a rather heavily trafficked road, where the source of CO2 is mostly vehicle
      exhaust, a rural unpolluted area, and a private kitchen where the major source of
      CO2 was gas combustion. Samplers were exposed to the free atmosphere for 3 days
      in order to allow collection of sufficient CO2 for delta(13)C analysis, then the
      collected CO2 was desorbed from the adsorbent with acid treatment, and directly
      analyzed by nondispersive infrared (NDIR) instrument. delta (13)C results
      confirmed that the samplers collected representative CO2 samples and no
      fractionation occurred during passive trapping, as also confirmed by an
      appositely designed experiment conducted in the laboratory. Passive sampling
      using CaO/Ca12Al14O33 75:25 w/w proved to be an easy and reliable method to
      collect atmospheric carbon dioxide for delta (13)C analysis in both indoor and
      outdoor places.

PMID- 24281684
TI  - Temporal characteristics of black carbon concentrations and its potential
      emission sources in a southern Taiwan industrial urban area.
AB  - This study investigates the temporal characteristics of black carbon and its
      potential emission sources, as well as the fractions of BC in PM2.5 levels in
      Kaohsiung urban area, which is an industrial city in southern Taiwan.
      Concentrations of BC and PM2.5 are monitored continuously from March 2006 to
      February 2010, using an aethalometer and a tapered element oscillating
      microbalance monitor. Additionally, the presence of organic compounds (or UV
      enhanced species) in particles at the sampling site is determined using the Delta
      C (UVBC-BC) value. According to long-term measurement results, BC and PM2.5
      concentrations are 3.33 and 34.0 MUg m(-3), respectively, in the Kaohsiung urban
      area. The ratio of BC/PM2.5 is approximately 11 %. Low concentration of BC and
      PM2.5 in the summer of this study period is mostly likely owing to meteorological
      conditions that favored dispersion of local air pollutants. Nevertheless, BC
      concentrations peaked markedly during morning hours (7:00-11:00), likely owing to
      local traffic congestion. Measurement results suggest that BC is released from
      local traffic activities and emitted from industrial activities at this sampling
      site. Additionally, Delta-C values are significantly higher than zero during
      January-March and November-December periods in this industrial urban area,
      implying that UV enhanced species can be observed. At this sampling site, these
      UV enhanced species do not only originate from household activity and solid waste
      burning but also release from industrial activities. The elevated Delta-C values
      during nighttime (18:00-6:00) in the autumn and winter seasons are likely related
      to those UV enhanced species in the atmosphere, which can be condensed on
      particle surface under low temperature conditions. According to long-term
      measurement results, significantly positive Delta-C values can be observed under
      temperatures <20  degrees C and relative humidity of 60-75 % in this study.
      Despite the household activity and solid waste burning, the major sources of
      particles that are bound with UV enhanced species in this sampling site are
      industrial parks and a coal-fired power plant.

PMID- 24281685
TI  - Guidelines for anti-scatter grid use in pediatric digital radiography.
AB  - BACKGROUND: Pediatric radiography presents unique challenges in balancing image
      quality and patient dose. Removing the anti-scatter grid reduces patient dose but
      also reduces image contrast. The benefit of using an anti-scatter grid decreases
      with decreasing patient size. OBJECTIVE: To determine patient thickness
      thresholds for anti-scatter grid use by comparing scatter-to-primary ratio for
      progressively thinner patients without a grid to the scatter-to-primary ratio for
      a standard adult patient with a grid. MATERIALS AND METHODS: We used Solid
      WaterTM phantoms ranging in thickness from 7 cm to 16 cm to simulate pediatric
      abdomens. The scatter-to-primary ratio without a grid was measured for each
      thickness at 60 kVp, 70 kVp and 80 kVp for X-ray fields of view (FOV) of 378
      cm(2), 690 cm(2) and 1,175 cm(2) using indirect digital radiography (iDR) and
      computed radiography (CR). We determined thresholds for anti-scatter grid use by
      comparing the intersection of a fit of scatter-to-primary ratio versus patient
      thickness with a standard adult scatter-to-primary ratio measured for a 23-cm
      phantom thickness at 80 kVp with an anti-scatter grid. Dose area product (DAP)
      was also calculated. RESULTS: The scatter-to-primary ratio depended strongly on
      FOV and weakly on kVp; however DAP increased with decreasing kVp. Threshold
      thicknesses for grid use varied from 5 cm for a 14 * 17-cm FOV using iDR to 12 cm
      for an 8 * 10-cm FOV using computed radiography. CONCLUSIONS: Removing the anti
      scatter grid for small patients reduces patient dose without a substantial
      increase in scatter-to-primary ratio when the FOV is restricted appropriately.
      Radiologic technologists should base anti-scatter grid use on patient thickness
      and FOV rather than age.

PMID- 24281686
TI  - Olive without a cause: the story of infantile hypertrophic pyloric stenosis.
AB  - For many diseases and medical conditions the clinical recognition and the
      development of accurate diagnostic methods and the etiological cause precede
      effective treatment. In the case of infantile hypertrophic pyloric stenosis
      (HPS), this sequence of events did not happen. Clinical recognition of the entity
      proceeded directly to the development of curative treatment. Reliable diagnostic
      imaging methods followed, but a definitive etiology has not been elucidated. This
      paper reviews the historical aspects of hypertrophic pyloric stenosis, discusses
      how and why it took so long for this not uncommon disease to be recognized, and
      highlights the physicians who changed an often fatal disease into an easily
      diagnosed and treated minor affliction. 

PMID- 24281687
TI  - Open-source products for a lighting experiment device.
AB  - The capabilities of open-source software and microcontrollers were used to
      construct a device for controlled lighting experiments. The device was designed
      to ascertain whether individuals with certain color vision deficiencies were able
      to discriminate between the red and white lights in fielded systems on the basis
      of luminous intensity. The device provided the ability to control the timing and
      duration of light-emitting diode (LED) and incandescent light stimulus
      presentations, to present the experimental sequence and verbal instructions
      automatically, to adjust LED and incandescent luminous intensity, and to display
      LED and incandescent lights with various spectral emissions. The lighting device
      could easily be adapted for experiments involving flashing or timed presentations
      of colored lights, or the components could be expanded to study areas such as
      threshold light perception and visual alerting systems. 

PMID- 24281688
TI  - An extended genovo metagenomic assembler by incorporating paired-end information.
AB  - Metagenomes present assembly challenges, when assembling multiple genomes from
      mixed reads of multiple species. An assembler for single genomes can't adapt well
      when applied in this case. A metagenomic assembler, Genovo, is a de novo
      assembler for metagenomes under a generative probabilistic model. Genovo
      assembles all reads without discarding any reads in a preprocessing step, and is
      therefore able to extract more information from metagenomic data and, in
      principle, generate better assembly results. Paired end sequencing is currently
      widely-used yet Genovo was designed for 454 single end reads. In this research,
      we attempted to extend Genovo by incorporating paired-end information, named
      Xgenovo, so that it generates higher quality assemblies with paired end reads.
      First, we extended Genovo by adding a bonus parameter in the Chinese Restaurant
      Process used to get prior accounts for the unknown number of genomes in the
      sample. This bonus parameter intends for a pair of reads to be in the same contig
      and as an effort to solve chimera contig case. Second, we modified the sampling
      process of the location of a read in a contig. We used relative distance for the
      number of trials in the symmetric geometric distribution instead of using
      distance between the offset and the center of contig used in Genovo. Using this
      relative distance, a read sampled in the appropriate location has higher
      probability. Therefore a read will be mapped in the correct location. Results of
      extensive experiments on simulated metagenomic datasets from simple to complex
      with species coverage setting following uniform and lognormal distribution showed
      that Xgenovo can be superior to the original Genovo and the recently proposed
      metagenome assembler for 454 reads, MAP. Xgenovo successfully generated longer
      N50 than Genovo and MAP while maintaining the assembly quality even for very
      complex metagenomic datasets consisting of 115 species. Xgenovo also demonstrated
      the potential to decrease the computational cost. This means that our strategy
      worked well. The software and all simulated datasets are publicly available
      online at http://xgenovo.dna.bio.keio.ac.jp. 

PMID- 24281689
TI  - Daytime relapse of the mean radiant temperature based on the six-directional
      method under unobstructed solar radiation.
AB  - This study contributes to the knowledge about the capabilities of the popular
      "six-directional method" describing the radiation fields outdoors. In Taiwan,
      measurements were carried out with three orthogonally placed net radiometers to
      determine the mean radiant temperature (T(mrt)). The short- and long-wave
      radiation flux densities from the six perpendicular directions were recorded in
      the daylight hours of 12 days. During unobstructed direct irradiation, a specific
      daytime relapse was found in the temporal course of the T(mrt) values referring
      to the reference shapes of a standing man and also of a sphere. This relapse can
      be related to the short-wave fluxes reaching the body from the lateral
      directions. Through deeper analysis, an instrumental shortcoming of the six
      directional technique was discovered. The pyranometer pairs of the same net
      radiometer have a 10-15-min long "blind spot" when the sun beams are nearly
      perpendicular to them. The blind-spot period is supposed to be shorter with
      steeper solar azimuth curve on the daylight period. This means that the locations
      with lower geographical latitude, and the summertime measurements, are affected
      less by this instrumental problem. A methodological shortcoming of the six
      directional technique was also demonstrated. Namely, the sum of the short-wave
      flux densities from the lateral directions is sensitive to the orientation of the
      radiometers, and therefore by deviating from the original directions, the T(mrt)
      decrease on clear sunny days will occur in different times and will be different
      in extent.

PMID- 24281690
TI  - Design and evaluation of a PEGylated lipopeptide equipped with drug-interactive
      motifs as an improved drug carrier.
AB  - Micelles are attractive delivery systems for hydrophobic drugs due to their small
      size and the ease of application. However, the limited drug loading capacity and
      the intrinsic poor stability of drug-loaded formulations represent two major
      issues for some micellar systems. In this study, we designed and synthesized a
      micelle-forming PEG-lipopeptide conjugate with two Fmoc groups located at the
      interfacial region, and two oleoyl chains as the hydrophobic core. The
      significance of Fmoc groups as a broadly applicable drug-interactive motif that
      enhances the carrier-drug interaction was examined using eight model drugs of
      diverse structures. Compared with an analogue without carrying a Fmoc motif,
      PEG5000-(Fmoc-OA)2 demonstrated a lower value of critical micelle concentration
      and three-fold increases of loading capacity for paclitaxel (PTX). These micelles
      showed tubular structures and small particle sizes (~70 nm), which can be
      lyophilized and readily reconstituted with water without significant changes in
      particle sizes. Fluorescence quenching study illustrated the Fmoc/PTX pi-pi
      stacking contributes to the carrier/PTX interaction, and drug-release study
      demonstrated a much slower kinetics than Taxol, a clinically used PTX
      formulation. PTX/PEG5000-(Fmoc-OA)2 mixed micelles exhibited higher levels of
      cytotoxicity than Taxol in several cancer cell lines and more potent inhibitory
      effects on tumor growth than Taxol in a syngeneic murine breast cancer model
      (4T1.2). We have further shown that seven other drugs can be effectively
      formulated in PEG5000-(Fmoc-OA)2 micelles. Our study suggests that micelle
      forming PEG-lipopeptide surfactants with interfacial Fmoc motifs may represent a
      promising formulation platform for a broad range of drugs with diverse
      structures.

PMID- 24281691
TI  - A novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal
      antibody derived from two different cell lines using simultaneous crossover
      design.
AB  - A parallel study design with a large number of subjects has been a typical path
      for pharmacokinetic (PK) biocomparability assessment of biotherapeutics with long
      half-lives and immunogenic propensity, for example, monoclonal antibodies (mAb).
      A recently published innovative bioanalytical method that can quantify mAb
      produced from two different cell lines in the same sample opened an avenue to
      exploring a simultaneous crossover study design for PK biocomparability
      assessment of biotherapeutics. Siltuximab, a chimeric IgG1 mAb-targeting
      interleukin-6, was studied as an example. The pharmacokinetic biocomparability of
      siltuximab derived from mouse myeloma (Sp2/0) cells and Chinese hamster ovary
      cells was previously assessed and demonstrated in a clinical PK biocomparability
      study that enrolled more than 140 healthy subjects using a parallel trial design.
      The biocomparability was successfully shown in six cynomolgus monkeys in a
      preclinical proof-of-concept study using the new crossover study design supported
      by the analytical method. The impact of antidrug antibodies on the assessment of
      biocomparability was minimal. This novel approach opened up a new arena for the
      evaluation of PK biocomparability of biotherapeutics with unique molecular
      signatures such as a mAb derived from different cell lines. 

PMID- 24281692
TI  - A coumarin derivative as a fluorogenic glycoproteomic probe for biological
      imaging.
AB  - Fluorescence imaging in living cells is typically carried out using a
      functionalized fluorescent dye. But it often causes strong background noise under
      many conditions where washing is not applicable. Here, we report on a coumarin
      based fluorogenic probe, which can be used as a bioorthogonal-labeling tool for
      glycoproteins. The results indicated that the probe was able to image
      glycoproteins in living cells and it may also be suitable for intracellular
      imaging. 

PMID- 24281693
TI  - Toward a unifying definition: response to 'The concept of mental pain'.

PMID- 24281694
TI  - Revisiting amino acid substitution matrices for identifying distantly related
      proteins.
AB  - MOTIVATION: Although many amino acid substitution matrices have been developed,
      it has not been well understood which is the best for similarity searches,
      especially for remote homology detection. Therefore, we collected information
      related to existing matrices, condensed it and derived a novel matrix that can
      detect more remote homology than ever. RESULTS: Using principal component
      analysis with existing matrices and benchmarks, we developed a novel matrix,
      which we designate as MIQS. The detection performance of MIQS is validated and
      compared with that of existing general purpose matrices using SSEARCH with
      optimized gap penalties for each matrix. Results show that MIQS is able to detect
      more remote homology than the existing matrices on an independent dataset. In
      addition, the performance of our developed matrix was superior to that of CS
      BLAST, which was a novel similarity search method with no amino acid matrix. We
      also evaluated the alignment quality of matrices and methods, which revealed that
      MIQS shows higher alignment sensitivity than that with the existing matrix series
      and CS-BLAST. Fundamentally, these results are expected to constitute good proof
      of the availability and/or importance of amino acid matrices in sequence
      analysis. Moreover, with our developed matrix, sophisticated similarity search
      methods such as sequence-profile and profile-profile comparison methods can be
      improved further. AVAILABILITY AND IMPLEMENTATION: Newly developed matrices and
      datasets used for this study are available at http://csas.cbrc.jp/Ssearch/.

PMID- 24281695
TI  - Flexible analysis of RNA-seq data using mixed effects models.
AB  - MOTIVATION: Most methods for estimating differential expression from RNA-seq are
      based on statistics that compare normalized read counts between treatment
      classes. Unfortunately, reads are in general too short to be mapped unambiguously
      to features of interest, such as genes, isoforms or haplotype-specific isoforms.
      There are methods for estimating expression levels that account for this source
      of ambiguity. However, the uncertainty is not generally accounted for in
      downstream analysis of gene expression experiments. Moreover, at the individual
      transcript level, it can sometimes be too large to allow useful comparisons
      between treatment groups. RESULTS: In this article we make two proposals that
      improve the power, specificity and versatility of expression analysis using RNA
      seq data. First, we present a Bayesian method for model selection that accounts
      for read mapping ambiguities using random effects. This polytomous model
      selection approach can be used to identify many interesting patterns of gene
      expression and is not confined to detecting differential expression between two
      groups. For illustration, we use our method to detect imprinting, different types
      of regulatory divergence in cis and in trans and differential isoform usage, but
      many other applications are possible. Second, we present a novel collapsing
      algorithm for grouping transcripts into inferential units that exploits the
      posterior correlation between transcript expression levels. The aggregate
      expression levels of these units can be estimated with useful levels of
      uncertainty. Our algorithm can improve the precision of expression estimates when
      uncertainty is large with only a small reduction in biological resolution.
      AVAILABILITY AND IMPLEMENTATION: We have implemented our software in the mmdiff
      and mmcollapse multithreaded C++ programs as part of the open-source MMSEQ
      package, available on https://github.com/eturro/mmseq.

PMID- 24281696
TI  - mCSM: predicting the effects of mutations in proteins using graph-based
      signatures.
AB  - MOTIVATION: Mutations play fundamental roles in evolution by introducing
      diversity into genomes. Missense mutations in structural genes may become either
      selectively advantageous or disadvantageous to the organism by affecting protein
      stability and/or interfering with interactions between partners. Thus, the
      ability to predict the impact of mutations on protein stability and interactions
      is of significant value, particularly in understanding the effects of Mendelian
      and somatic mutations on the progression of disease. Here, we propose a novel
      approach to the study of missense mutations, called mCSM, which relies on graph
      based signatures. These encode distance patterns between atoms and are used to
      represent the protein residue environment and to train predictive models. To
      understand the roles of mutations in disease, we have evaluated their impacts not
      only on protein stability but also on protein-protein and protein-nucleic acid
      interactions. RESULTS: We show that mCSM performs as well as or better than other
      methods that are used widely. The mCSM signatures were successfully used in
      different tasks demonstrating that the impact of a mutation can be correlated
      with the atomic-distance patterns surrounding an amino acid residue. We showed
      that mCSM can predict stability changes of a wide range of mutations occurring in
      the tumour suppressor protein p53, demonstrating the applicability of the
      proposed method in a challenging disease scenario. AVAILABILITY AND
      IMPLEMENTATION: A web server is available at
      http://structure.bioc.cam.ac.uk/mcsm.

PMID- 24281697
TI  - Home testing past, present and future: lessons learned and implications for HIV
      home tests.
AB  - The recent approval in the United States of the first rapid home test to diagnose
      HIV raises questions about its potential use and impact. We reviewed the existing
      literature on the unassisted use of home tests involving self-collection and
      testing of biological samples by untrained users-including existing HIV self
      testing studies-to shed some light on what can be expected from the availability
      of the HIV home test. The studies reviewed showed that most participants could
      properly perform home tests, obtain accurate results, and interpret them-yielding
      high correlations with laboratory and health-professional performed tests. Users
      often had trouble performing blood-based tests. Participants generally understood
      the need to confirm positive test results. Materials accompanying HIV home tests
      should emphasize symptoms of acute infection and the need for additional testing
      when recent infection is suspected. Different home-test-based screening
      modalities, personalized HIV-counseling resources and HIV home test impact
      evaluation methods should be studied. 

PMID- 24281698
TI  - Improving the collection of knowledge, attitude and practice data with community
      surveys: a comparison of two second-stage sampling methods.
AB  - BACKGROUND: Second-stage sampling techniques, including spatial segmentation, are
      widely used in community health surveys when reliable household sampling frames
      are not available. In India, an unresearched technique for household selection is
      used in eight states, which samples the house with the last marriage or birth as
      the starting point. Users question whether this last-birth or last-marriage
      (LBLM) approach introduces bias affecting survey results. METHODS: We conducted
      two simultaneous population-based surveys. One used segmentation sampling; the
      other used LBLM. LBLM sampling required modification before assessment was
      possible and a more systematic approach was tested using last birth only. We
      compared coverage proportions produced by the two independent samples for six
      malaria indicators and demographic variables (education, wealth and caste). We
      then measured the level of agreement between the caste of the selected
      participant and the caste of the health worker making the selection. RESULTS: No
      significant difference between methods was found for the point estimates of six
      malaria indicators, education, caste or wealth of the survey participants (range
      of P: 0.06 to >0.99). A poor level of agreement occurred between the caste of the
      health worker used in household selection and the caste of the final participant,
      (Kappa = 0.185), revealing little association between the two, and thereby
      indicating that caste was not a source of bias. CONCLUSIONS: Although LBLM was
      not testable, a systematic last-birth approach was tested. If documented concerns
      of last-birth sampling are addressed, this new method could offer an acceptable
      alternative to segmentation in India. However, inter-state caste variation could
      affect this result. Therefore, additional assessment of last birth is required
      before wider implementation is recommended.

PMID- 24281699
TI  - Formative evaluation of a practice-based smoking cessation program for diverse
      populations.
AB  - BACKGROUND: Smoking rates are higher among those living at or below poverty and
      among persons with lower levels of education. We report on a formative research
      project examining patient perceptions of tobacco cessation strategies among
      diverse, low socioeconomic, urban smokers cared for in community-based primary
      care medical offices. METHOD: We conducted 10 focus groups among low
      socioeconomic status participants recruited from urban primary care medical
      offices in Buffalo and Niagara Falls, New York. Participants included current or
      former smokers, who were stratified by age-group (18-39 years and 40+ years). The
      focus groups discussed perceptions of tobacco cessation strategies, previous quit
      attempts, and use/attitudes regarding technology and social media as potential
      platforms for cessation support. RESULTS: Participants (n = 96) included
      predominantly African Americans (n = 62, 65%) and European Americans (n = 16,
      16%); 56% were older than 40 years and 92% were low income. Most participants
      were supportive of cessation message delivery via phone; however, the age-groups
      varied in their attitudes on quitting smoking, desired frequency of phone
      contacts, and social media usage. Participants aged 18 to 39 years reported more
      Internet use, greater use of text messaging, and were more open to health
      information via social media. CONCLUSIONS: Based on significant variation between
      younger and older smokers' perceptions of tobacco addiction and use of
      communication technologies, it appears reasonable to stratify the content and
      platform of health messaging by the target age-group.

PMID- 24281700
TI  - Large area, facile oxide nanofabrication via step-and-flash imprint lithography
      of metal-organic hybrid resins.
AB  - Step-and-flash imprint lithography (S-FIL) is a wafer-scale, high-resolution
      nanoimprint technique capable of expansion of nanoscale patterns via serial
      patterning of imprint fields. While S-FIL patterning of organic resins is well
      known, patterning of metal-organic resins followed by calcination to form
      structured oxide films remains relatively unexplored. However, with calcination
      shrinkage, there is tremendous potential utility in easing accessibility of
      arbitrary nanostructures at 20 nm resolution and below. However, barriers to
      commercial adoption exist due to difficulties in formulating polymerizable oxide
      precursors with good dispensability, long shelf life, and resistance to auto
      homopolymerization. Here we propose a solution to these issues in the form of a
      versatile resin formulation scheme that is applicable to a host of functional
      oxides (Al2O3, HfO2, TiO2, ZrO2, Ta2O5, and Nb2O5). This scheme utilizes a
      reaction of metal alkoxides with 2-(methacryloyloxy)ethyl acetoacetate (MAEAA), a
      polymerizable chelating agent. Formation of these inorganic coordination
      complexes enables remarkable resistance to auto-homopolymerization, greatly
      improving dispensability and shelf life, thus enabling full scale-up of this
      facile nanofabrication approach. Results include successively imprinted fields
      consisting of 100 nm linewidth gratings. Isothermal calcination of these
      structures resulted in corresponding shrinkage of 75-80% without loss of
      mechanical integrity or aspect ratio, resulting in 20 nm linewidth oxide
      nanostructures. 

PMID- 24281706
TI  - Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is
      Further Increased by Combining Pertuzumab with Trastuzumab.
AB  - ErbB2 is an important oncogenic protein involved in carcinogenesis of, among
      others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found
      in almost 20% of breast cancers, and this results in proliferative and anti
      apoptotic signalling. ErbB2 is therefore an important treatment target.
      Antibodies recognizing full-length ErbB2 are clinically established, and drugs
      targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90) are under clinical
      evaluation. We have investigated effects of the ErbB2-binding antibodies
      trastuzumab and pertuzumab alone and in combination, as well as the effect of the
      antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm
      the notion that combination of different ErbB2-binding antibodies more
      efficiently down-regulates ErbB2 than does one antibody in isolation.
      Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated
      upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors.
      The combination of anti-ErbB2 antibodies, and especially the combination of
      antibodies with 17-AAG, did also increase the inhibition of Akt activation of
      either agent, which could suggest an anti-proliferative effect. In such case,
      combining these agents could be beneficial in treatment of tumors not responding
      to trastuzumab only. 

PMID- 24281707
TI  - Chemotherapeutic interventions against tuberculosis.
AB  - Tuberculosis is the second leading cause of infectious deaths globally. Many
      effective conventional antimycobacterial drugs have been available, however,
      emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug
      resistant tuberculosis (XDR-TB) has overshadowed the effectiveness of the current
      first and second line drugs. Further, currently available agents are complicated
      by serious side effects, drug interactions and long-term administration. This has
      prompted urgent research efforts in the discovery and development of new anti
      tuberculosis agent(s). Several families of compounds are currently being explored
      for the treatment of tuberculosis. This review article presents an account of the
      existing chemotherapeutics and highlights the therapeutic potential of emerging
      molecules that are at different stages of development for the management of
      tuberculosis disease. 

PMID- 24281708
TI  - Association of marijuana use and cyclic vomiting syndrome.
AB  - Cannabis use has become one of the most commonly abused drugs in the world. It is
      estimated that each year 2.6 million individuals in the USA become new users and
      most are younger than 19 years of age. Reports describe marijuana use as high as
      40-50% in male Cyclic Vomiting Syndrome patients. It is this interest in cannabis
      in the World, coupled with recognition of a cyclic vomiting illness associated
      with its chronic use that beckons a review of the most current articles, as well
      as a contribution from our own experiences in this area. The similarities we have
      demonstrated for both cannibinoid hyperemesis syndrome and cyclic vomiting make
      the case that cannibinoid hyperemesis syndrome is a subset of patients who have
      the diagnoses of cyclic vomiting syndrome and the role of marijuana should always
      be considered in the diagnosis of CVS, particularly in males. 

PMID- 24281709
TI  - Probiotics and atopic dermatitis in children.
AB  - There is increasing interest in the potential beneficial role of probiotic
      supplementation in the prevention and treatment of atopic diseases in children.
      Probiotics are defined as ingested live microorganisms that, when administered in
      an adequate amount, confer a health benefit to the host. They are mainly
      represented by Lactobacilli and Bifidobacteria. Several epidemiological data
      demonstrate that intestinal microflora of atopic children is different from the
      one of healthy children. Many literature data show that probiotics may modulate
      the intestinal microflora composition and may have immunomodulatory effect. Based
      on this hypothesis, probiotics are supposed to confer benefits to allergic
      diseases. Administration of probiotics when a natural population of indigenous
      intestinal bacteria is still developing could theoretically influence immune
      development by favoring the balance between Th1 and Th2 inflammatory responses.
      For this reason, some studies have evaluated the potential impact of probiotics
      supplementation in the prevention of atopic dermatitis, with contrasting results.
      Clinical improvement in immunoglobulin (Ig)E-sensitized (atopic) eczema following
      probiotic supplementation has been reported in some published studies and the
      therapeutic effects of probiotics on atopic dermatitis seemed to be encouraging.
      However, as far as the usefulness of probiotics as a prevention strategy is
      concerned, results are still inconclusive. In fact, the clinical benefits of
      probiotic therapy depend upon numerous factors, such as the type of bacteria,
      dosing regimen, delivery method and other underlying host factors, such as age
      and diet. More studies are still needed to definitively prove the role of
      probiotics in the treatment of allergic eczema. 

PMID- 24281710
TI  - Synthesis, Reactions and Evaluation of the Antimicrobial Activity of Some 4-(p
      Halophenyl)-4H-naphthopyran, Pyranopyrimidine and Pyranotriazolopyrimidine
      Derivatives.
AB  - A series of naphthopyran derivatives 3a-f were prepared. Reaction of 2-amino-4-(p
      chlorophenyl)-7-methoxy-4H-naphtho[2,1-b]pyran-3-carbonitrile (3b) with Ac2O
      afforded two products, 2-acetylamino-7-methoxy-4-(p-chlorophenyl)-4H-naphtho-[2,1
      b]pyran-3-carbonitrile (4) and 10,11-dihydro-3-methoxy-9-methyl-12-(p-chloro
      phenyl)-12H-naphtho[2,1-b]pyran[2,3-d]pyrimidine-11-one (5) and treatment of 3b
      with benzoyl chloride gave the pyranopyrimidin-11-one derivative 6. While
      treatment of 3b with formamide afforded 11-amino-3-methoxy-12-(p-chlorophenyl)
      12H-naphtho[2,1-b]pyrano[2,3-d]pyrimidine (7). Reaction of 3b with triethyl
      orthoformate gave the corresponding 2-ethoxymethyleneamino-7-methoxy-4-(p
      chlorophenyl)-4H-naphtho-[2,1-b]pyran-3-carbonitrile (8). Hydrazinolysis of 8 in
      EtOH at room temperature yielded 10-amino-10,11-dihydro-11-imino-3-methoxy-12-(p
      chlorophenyl)-12H-naphtho[2,1-b]pyrano-[2,3-d]pyrimidine (9), while aminolysis of
      8 with methylamine or dimethylamine gave the corresponding pyranopyrimidine and
      N,N-dimethylaminomethylene derivatives 10 and 11. Condensation of 9 with some
      carboxylic acid derivatives afforded triazolopyrimidine derivatives 12-16, while
      reaction of 9 with benzaldehyde gave 10-benzalamino-10,11-dihydro-11-imino-3
      methoxy-12-(p-chlorophenyl)12H-naphtho[2,1-b]pyrano[2,3-d]pyrimidine (17). The
      structures of the newly synthesized compounds were confirmed by spectral data.
      The synthesized compounds were also screened for their antimicrobial activity. 

PMID- 24281712
TI  - In memoriam: Lloyd F. Mayer, MD June 21, 1952-September 5, 2013.

PMID- 24281711
TI  - The influence of estrogens on the biological and therapeutic actions of growth
      hormone in the liver.
AB  - GH is main regulator of body growth and composition, somatic development,
      intermediate metabolism and gender-dependent dimorphism in mammals. The liver is
      a direct target of estrogens because it expresses estrogen receptors which are
      connected with development, lipid metabolism and insulin sensitivity, hepatic
      carcinogenesis, protection from drug-induced toxicity and fertility. In addition,
      estrogens can modulate GH actions in liver by acting centrally, regulating
      pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5
      signalling pathway. Therefore, the interactions of estrogens with GH actions in
      liver are biologically and clinically relevant because disruption of GH signaling
      may cause alterations of its endocrine, metabolic, and gender differentiated
      functions and it could be linked to dramatic impact in liver physiology during
      development as well as in adulthood. Finally, the interplay of estrogens with GH
      is relevant because physiological roles these hormones have in human, and the
      widespread exposition of estrogen or estrogen-related compounds in human. This
      review highlights the importance of these hormones in liver physiology as well as
      how estrogens modulate GH actions in liver which will help to improve the
      clinical use of these hormones. 

PMID- 24281713
TI  - Scalable fabrication of high-performance and flexible graphene strain sensors.
AB  - Graphene strain sensors have promising prospects of applications in detecting
      human motion. However, the shortage of graphene growth and patterning techniques
      has become a challenging issue hindering the application of graphene strain
      sensors. Therefore, we propose wafer-scale flexible strain sensors with high
      performance, which can be fabricated in one-step laser scribing. The graphene
      films could be obtained by directly reducing graphene oxide film in a Light
      Scribe DVD burner. The gauge factor (GF) of the graphene strain sensor (10 mm *
      10 mm square) is 0.11. In order to enhance the GF further, graphene micro-ribbons
      (20 MUm width, 0.6 mm long) has been used as strain sensors, of which the GF is
      up to 9.49. The devices may conform to various application requirements, such as
      high GF for low-strain applications and low GF for high deformation applications.
      The work indicates that laser scribed flexible graphene strain sensors could be
      widely used in medical-sensing, bio-sensing, artificial skin and many other
      areas. 

PMID- 24281714
TI  - Distinct signaling cascades of TREM-1, TLR and NLR in neutrophils and monocytic
      cells.
AB  - Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important
      mediator of innate inflammatory responses in microbial infections and sepsis.
      TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of
      proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP
      kinases as well as rapid Ca(2+) mobilization. However, a detailed understanding
      of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1
      signaling hierarchy in monocytic cells and found that the acute myeloid leukemia
      cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared
      essential signaling molecules of the TREM-1, TLR and NLR cascade in MUTZ-3 cells
      as well as primary monocytes or PMN by Western blot analysis. These studies
      confirmed the essential role of phosphatidyl inositide 3-kinase (PI3K) and
      p38MAPK in the TREM-1 as well as the TLR or NLR cascade of monocytic cells.
      Importantly, PI3K and p38MAPK signals in monocytic cells both control Ca(2+)
      mobilization and are directly connected in the TREM-1 signaling hierarchy, which
      contrasts previous results obtained in PMN. Taken together, our results indicate
      cell type-specific differences in the TREM-1 signaling cascade and contribute to
      an enhanced understanding of the regulation of innate inflammatory responses.

PMID- 24281715
TI  - Integrated smart electrochromic windows for energy saving and storage
      applications.
AB  - A self-powered electrochromic smart window with tunable transmittance driven by
      dye-sensitized solar cells has been designed, which also acts as a photocharged
      electrochromic supercapacitor with high areal capacitance and reversible color
      changes. 

PMID- 24281716
TI  - Ralstonia solanacearum requires PopS, an ancient AvrE-family effector, for
      virulence and To overcome salicylic acid-mediated defenses during tomato
      pathogenesis.
AB  - During bacterial wilt of tomato, the plant pathogen Ralstonia solanacearum
      upregulates expression of popS, which encodes a type III-secreted effector in the
      AvrE family. PopS is a core effector present in all sequenced strains in the R.
      solanacearum species complex. The phylogeny of popS mirrors that of the species
      complex as a whole, suggesting that this is an ancient, vertically inherited
      effector needed for association with plants. A popS mutant of R. solanacearum
      UW551 had reduced virulence on agriculturally important Solanum spp., including
      potato and tomato plants. However, the popS mutant had wild-type virulence on a
      weed host, Solanum dulcamara, suggesting that some species can avoid the effects
      of PopS. The popS mutant was also significantly delayed in colonization of tomato
      stems compared to the wild type. Some AvrE-type effectors from
      gammaproteobacteria suppress salicylic acid (SA)-mediated plant defenses,
      suggesting that PopS, a betaproteobacterial ortholog, has a similar function.
      Indeed, the popS mutant induced significantly higher expression of tomato SA
      triggered pathogenesis-related (PR) genes than the wild type. Further,
      pretreatment of roots with SA exacerbated the popS mutant virulence defect.
      Finally, the popS mutant had no colonization defect on SA-deficient NahG
      transgenic tomato plants. Together, these results indicate that this conserved
      effector suppresses SA-mediated defenses in tomato roots and stems, which are R.
      solanacearum's natural infection sites. Interestingly, PopS did not trigger
      necrosis when heterologously expressed in Nicotiana leaf tissue, unlike the AvrE
      homolog DspEPcc from the necrotroph Pectobacterium carotovorum subsp.
      carotovorum. This is consistent with the differing pathogenesis modes of necrosis
      causing gammaproteobacteria and biotrophic R. solanacearum. IMPORTANCE: The type
      III-secreted AvrE effector family is widely distributed in high-impact plant
      pathogenic bacteria and is known to suppress plant defenses for virulence. We
      characterized the biology of PopS, the only AvrE homolog made by the bacterial
      wilt pathogen Ralstonia solanacearum. To our knowledge, this is the first study
      of R. solanacearum effector function in roots and stems, the natural infection
      sites of this pathogen. Unlike the functionally redundant R. solanacearum
      effectors studied to date, PopS is required for full virulence and wild-type
      colonization of two natural crop hosts. R. solanacearum is a biotrophic pathogen
      that causes a nonnecrotic wilt. Consistent with this, PopS suppressed plant
      defenses but did not elicit cell death, unlike AvrE homologs from necrosis
      causing plant pathogens. We propose that AvrE family effectors have functionally
      diverged to adapt to the necrotic or nonnecrotic lifestyle of their respective
      pathogens.

PMID- 24281717
TI  - Proteomic and transcriptomic analyses of "Candidatus Pelagibacter ubique"
      describe the first PII-independent response to nitrogen limitation in a free
      living Alphaproteobacterium.
AB  - Nitrogen is one of the major nutrients limiting microbial productivity in the
      ocean, and as a result, most marine microorganisms have evolved systems for
      responding to nitrogen stress. The highly abundant alphaproteobacterium
      "Candidatus Pelagibacter ubique," a cultured member of the order Pelagibacterales
      (SAR11), lacks the canonical GlnB, GlnD, GlnK, and NtrB/NtrC genes for regulating
      nitrogen assimilation, raising questions about how these organisms respond to
      nitrogen limitation. A survey of 266 Alphaproteobacteria genomes found these five
      regulatory genes nearly universally conserved, absent only in intracellular
      parasites and members of the order Pelagibacterales, including "Ca. Pelagibacter
      ubique." Global differences in mRNA and protein expression between nitrogen
      limited and nitrogen-replete cultures were measured to identify nitrogen stress
      responses in "Ca. Pelagibacter ubique" strain HTCC1062. Transporters for ammonium
      (AmtB), taurine (TauA), amino acids (YhdW), and opines (OccT) were all elevated
      in nitrogen-limited cells, indicating that they devote increased resources to the
      assimilation of nitrogenous organic compounds. Enzymes for assimilating amine
      into glutamine (GlnA), glutamate (GltBD), and glycine (AspC) were similarly
      upregulated. Differential regulation of the transcriptional regulator NtrX in the
      two-component signaling system NtrY/NtrX was also observed, implicating it in
      control of the nitrogen starvation response. Comparisons of the transcriptome and
      proteome supported previous observations of uncoupling between transcription and
      translation in nutrient-deprived "Ca. Pelagibacter ubique" cells. Overall, these
      data reveal a streamlined, PII-independent response to nitrogen stress in "Ca.
      Pelagibacter ubique," and likely other Pelagibacterales, and show that they
      respond to nitrogen stress by allocating more resources to the assimilation of
      nitrogen-rich organic compounds. IMPORTANCE: Pelagibacterales are extraordinarily
      abundant and play a pivotal role in marine geochemical cycles, as one of the
      major recyclers of labile dissolved organic matter. They are also models for
      understanding how streamlining selection can reshape chemoheterotroph metabolism.
      Streamlining and its broad importance to environmental microbiology are emerging
      slowly from studies that reveal the complete genomes of uncultured organisms.
      Here, we report another remarkable example of streamlined metabolism in
      Pelagibacterales, this time in systems that control nitrogen assimilation.
      Pelagibacterales are major contributors to metatranscriptomes and metaproteomes
      from ocean systems, where patterns of gene expression are used to gain insight
      into ocean conditions and geochemical cycles. The data presented here supply
      background that is essential to interpreting data from field studies.

PMID- 24281718
TI  - The MARVEL domain protein Nce102 regulates actin organization and invasive growth
      of Candida albicans.
AB  - Invasive growth of the fungal pathogen Candida albicans into tissues promotes
      disseminated infections in humans. The plasma membrane is essential for
      pathogenesis because this important barrier mediates morphogenesis and invasive
      growth, as well as secretion of virulence factors, cell wall synthesis, nutrient
      import, and other processes. Previous studies showed that the Sur7 tetraspan
      protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome
      subdomains of the plasma membrane regulates a broad range of key functions,
      including cell wall synthesis, morphogenesis, and resistance to copper.
      Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was
      investigated. Nce102 belongs to the MARVEL domain protein family, which is
      implicated in regulating membrane structure and function. Deletion of NCE102 did
      not cause the broad defects seen in sur7Delta cells. Instead, the nce102Delta
      mutant displayed a unique phenotype in that it was defective in forming hyphae
      and invading low concentrations of agar but could invade well in higher agar
      concentrations. This phenotype was likely due to a defect in actin organization
      that was observed by phalloidin staining. In support of this, the invasive growth
      defect of a bni1Delta mutant that mislocalizes actin due to lack of the Bni1
      formin was also reversed at high agar concentrations. This suggests that a denser
      matrix provides a signal that compensates for the actin defects. The nce102Delta
      mutant displayed decreased virulence and formed abnormal hyphae in mice. These
      studies identify novel ways that Nce102 and the physical environment surrounding
      C. albicans regulate morphogenesis and pathogenesis. IMPORTANCE: The plasma
      membrane promotes virulence of the human fungal pathogen Candida albicans by
      acting as a protective barrier around the cell and mediating dynamic activities,
      such as morphogenesis, cell wall synthesis, secretion of virulence factors, and
      nutrient uptake. To better understand how the plasma membrane contributes to
      virulence, we analyzed a set of eight genes encoding MARVEL family proteins that
      are predicted to function in membrane organization. Interestingly, deletion of
      one gene, NCE102, caused a strong defect in formation of invasive hyphal growth
      in vitro and decreased virulence in mice. The nce102Delta mutant cells showed
      defects in actin organization that underlie the morphogenesis defect, since
      mutation of a known regulator of actin organization caused a similar defect.
      These studies identify a novel way in which the plasma membrane regulates the
      actin cytoskeleton and contributes to pathogenesis.

PMID- 24281719
TI  - Inhibitor of cysteine proteases is critical for motility and infectivity of
      Plasmodium sporozoites.
AB  - Malaria is transmitted when motile sporozoites are injected into the dermis by an
      infected female Anopheles mosquito. Inside the mosquito vector, sporozoites
      egress from midgut-associated oocysts and eventually penetrate the acinar cells
      of salivary glands. Parasite-encoded factors with exclusive vital roles in the
      insect vector can be studied by classical reverse genetics. Here, we
      characterized the in vivo roles of Plasmodium berghei falstatin/ICP (inhibitor of
      cysteine proteases). This protein was previously suggested to act as a protease
      inhibitor during erythrocyte invasion. We show by targeted gene disruption that
      loss of ICP function does not affect growth inside the mammalian host but causes
      a complete defect in sporozoite transmission. Sporogony occurred normally in icp(
      ) parasites, but hemocoel sporozoites showed a defect in continuous gliding
      motility and infectivity for salivary glands, which are prerequisites for
      sporozoite transmission to the mammalian host. Absence of ICP correlates with
      enhanced cleavage of circumsporozoite protein, in agreement with a role as a
      protease regulator. We conclude that ICP is essential for only the final stages
      of sporozoite maturation inside the mosquito vector. This study is the first
      genetic evidence that an ICP is necessary for the productive motility of a
      eukaryotic parasitic cell. IMPORTANCE: Cysteine proteases and their inhibitors
      are considered ideal drug targets for the treatment of a wide range of diseases,
      including cancer and parasitic infections. In protozoan parasites, including
      Leishmania, Trypanosoma, and Plasmodium, cysteine proteases play important roles
      in life cycle progression. A mouse malaria model provides an unprecedented
      opportunity to study the roles of a parasite-encoded inhibitor of cysteine
      proteases (ICP) over the entire parasite life cycle. By precise gene deletion, we
      found no evidence that ICP influences disease progression or parasite virulence.
      Instead, we discovered that this factor is necessary for parasite movement and
      malaria transmission from mosquitoes to mammals. This finding in a fast-moving
      unicellular protozoan has important implications for malaria intervention
      strategies and the roles of ICPs in the regulation of eukaryotic cell migration.

PMID- 24281720
TI  - Nitranilic acid hexahydrate, a novel benchmark system of the Zundel cation in an
      intrinsically asymmetric environment: spectroscopic features and hydrogen bond
      dynamics characterised by experimental and theoretical methods.
AB  - Nitranilic acid (2,5-dihydroxy-3,6-dinitro-2,5-cyclohexadiene-1,4-dione) as a
      strong dibasic acid in acidic aqueous media creates the Zundel cation, H5O2(+).
      The structural unit in a crystal comprises (H5O2)2(+) (2,5-dihydroxy-3,6-dinitro
      1,4-benzoquinonate)(2-) dihydrate where the Zundel cation reveals no symmetry,
      being an ideal case for studying proton dynamics and its stability. The Zundel
      cation and proton transfer dynamics are studied by variable-temperature X-ray
      diffraction, IR and solid-state NMR spectroscopy, and various quantum chemical
      methods, including periodic DFT calculations, ab initio molecular dynamics
      simulation, and quantization of nuclear motion along three fully coupled internal
      coordinates. The Zundel cation features a short H-bond with the O...O distance of
      2.433(2) A with an asymmetric placement of hydrogen. The proton potential is of a
      single well type and, due to the non-symmetric surroundings, of asymmetric shape.
      The formation of the Zundel cation is facilitated by the electronegative NO2
      groups. The employed spectroscopic techniques supported by calculations confirm
      the presence of a short H-bond with a complex proton dynamics.

PMID- 24281721
TI  - De novo design of functional proteins: Toward artificial hydrogenases.
AB  - Over the last 25 years, de novo design has proven to be a valid approach to
      generate novel, well-folded proteins, and most recently, functional proteins. In
      response to societal needs, this approach is been used increasingly to design
      functional proteins developed with an eye toward sustainable fuel production.
      This review surveys recent examples of bioinspired de novo designed peptide based
      catalysts, focusing in particular on artificial hydrogenases.

PMID- 24281722
TI  - From venoms to BBB shuttles: Synthesis and blood-brain barrier transport
      assessment of apamin and a nontoxic analog.
AB  - Venoms are currently the focus of many drug discovery programs because they
      contain highly bioactive and selective components. Among them, apamin, a peptide
      found in bee venom, has received considerable attention because of its affinity
      for certain potassium channels and also because of its interesting structure and
      high stability to extreme pH and temperatures. Although apamin has long been
      claimed to cross the blood-brain barrier (BBB), only a few studies have been
      performed producing controversial results. In this article, it is shown that not
      only apamin is indeed able to penetrate the BBB in a cell-based model but also
      that an analog reported to be nontoxic passes through this barrier. Furthermore,
      the permeability values obtained, together with some evidence of an active
      transport mechanism and an amazing stability to serum proteases, make these
      peptides promising candidates for BBB shuttles.

PMID- 24281724
TI  - The Sixth Peptide Engineering Meeting PEM6, Emory University Conference Center,
      Atlanta, Georgia, October 2 to 5, 2012.

PMID- 24281725
TI  - Automatic detection of the intima-media thickness in ultrasound images of the
      common carotid artery using neural networks.
AB  - Atherosclerosis is the leading underlying pathologic process that results in
      cardiovascular diseases, which represents the main cause of death and disability
      in the world. The atherosclerotic process is a complex degenerative condition
      mainly affecting the medium- and large-size arteries, which begins in childhood
      and may remain unnoticed during decades. The intima-media thickness (IMT) of the
      common carotid artery (CCA) has emerged as one of the most powerful tool for the
      evaluation of preclinical atherosclerosis. IMT is measured by means of B-mode
      ultrasound images, which is a non-invasive and relatively low-cost technique.
      This paper proposes an effective image segmentation method for the IMT
      measurement in an automatic way. With this purpose, segmentation is posed as a
      pattern recognition problem, and a combination of artificial neural networks has
      been trained to solve this task. In particular, multi-layer perceptrons trained
      under the scaled conjugate gradient algorithm have been used. The suggested
      approach is tested on a set of 60 longitudinal ultrasound images of the CCA by
      comparing the automatic segmentation with four manual tracings. Moreover, the
      intra- and inter-observer errors have also been assessed. Despite of the
      simplicity of our approach, several quantitative statistical evaluations have
      shown its accuracy and robustness. 

PMID- 24281726
TI  - Evolutionary conservation of early mesoderm specification by mechanotransduction
      in Bilateria.
AB  - The modulation of developmental biochemical pathways by mechanical cues is an
      emerging feature of animal development, but its evolutionary origins have not
      been explored. Here we show that a common mechanosensitive pathway involving beta
      catenin specifies early mesodermal identity at gastrulation in zebrafish and
      Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila
      mesoderm invagination trigger the phosphorylation of beta-catenin-tyrosine-667.
      This leads to the release of beta-catenin into the cytoplasm and nucleus, where
      it triggers and maintains, respectively, the expression of zebrafish brachyury
      orthologue notail and of Drosophila Twist, both crucial transcription factors for
      early mesoderm identity. The role of the beta-catenin mechanosensitive pathway in
      mesoderm identity has been conserved over the large evolutionary distance
      separating zebrafish and Drosophila. This suggests mesoderm mechanical induction
      dating back to at least the last bilaterian common ancestor more than 570 million
      years ago, the period during which mesoderm is thought to have emerged. 

PMID- 24281727
TI  - Social competence in pediatric brain tumor survivors: evaluating the psychometric
      properties of assessment tools.
AB  - PURPOSE: This study was conducted to identify and describe the instruments that
      have been used to measure social competence in pediatric brain tumor patients and
      to summarize the psychometric properties of the most common instruments used to
      measure social competence in pediatric brain tumor patients. METHODS: The
      following psychometric properties were assessed: (a) construct validity; (b)
      internal consistency reliability; (c) test retest and inter-rater reliability;
      and (d) responsiveness. Measures were evaluated based on published criteria for
      psychometric suitability. RESULTS: Ten studies met inclusion criteria for the
      current review. Based on review of these studies, the Social Skills Rating System
      (SSRS) yielded the most comprehensive data on psychometric properties.
      Psychometric properties for the SSRS were considered to be adequate in a
      pediatric brain tumor population. Specifically, the SSRS meets criteria for
      construct validity, internal consistency and responsiveness. Other commonly used
      measures included the CBCL/YSR, the PedsQL4.0 and the Revised Class Play each
      with sufficient psychometric properties. CONCLUSIONS: The SSRS is an appropriate
      tool to measure social competence in pediatric brain tumor patients. Data for
      inter-rater reliability and responsiveness in this population is still lacking.

PMID- 24281728
TI  - Testing the 'teachable moment' premise: does physical activity increase in the
      early survivorship phase?
AB  - PURPOSE: Little is known about objectively measured physical activity during the
      early survivorship period. This study measured physical activity, fatigue, and
      quality of life (QOL) in breast cancer patients over the first year after
      completion of chemotherapy and compared results to a matched non-cancer group.
      METHODS: Data was obtained from 24 breast cancer subjects (mean +/- SD) 50.9 +/-
      12.8 years at time points of 6 weeks, 6 months and 1 year after completion of
      adjuvant chemotherapy and from 20 matched women. The following variables were
      assessed, physical activity (RT3 accelerometer and International Physical
      Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief
      Fatigue Inventory). RESULTS: At 6 weeks after completion of chemotherapy, high
      levels of sedentary behaviour were found (6.8 +/- 1.9 h sedentary per day), which
      did not improve, and was no different to the comparison group (6.5 +/- 1.4 h).
      Less light activity was performed in the cancer cohort compared to the comparison
      group (p = 0.003). Body mass index (BMI) increased significantly in the cancer
      cohort (p = 0.015) and 1 year after chemotherapy finished only 13% (n = 3) had a
      BMI <25, while the comparable value was 45% (n = 9) in the non-cancer group. The
      QOL domain of cognitive function improved over the first 6 months (p = 0.034) but
      physical functioning declined (p = 0.008) over this time period. Fatigue did not
      change, and at the 1-year time point, 38% of the cancer patients (n = 11)
      reported high levels of fatigue. CONCLUSION: This study highlighted the
      unchanging sedentary behaviour and weight gain of breast cancer survivors during
      the first year after completion of chemotherapy, which may inform rehabilitation
      models in this population.

PMID- 24281729
TI  - The expression of IL-2 and IL-4 in CD4(+) T cells from mouse lymph nodes and
      spleen during HSV-1-induced facial palsy.
AB  - OBJECTIVE: Herpes simplex virus 1 (HSV-1) is regarded as an important underlying
      cause of Bell's palsy, but the immunologic mechanism remains unknown. Here, we
      employed a mouse facial paralysis model to investigate the expressions of CD4(+)
      T lymphocytes and interleukin (IL)-2 and -4 in the left draining cervical lymph
      nodes (LCLN) and spleen, as well as the inhibitory effects of glucocorticoids
      (GCs). METHODS: HSV-1 was inoculated into the surface of the posterior auricle to
      generate the facial paralysis model. The paralyzed mice were divided into three
      groups; in one group without any treatment, mice were killed at different time
      points, and those in the other two groups were injected with methylprednisolone
      sodium succinate (MPSS) or with a combination of MPSS and GC receptor blocker
      (RU486). The expression levels of CD4(+) T lymphocytes and CD4(+)-IL-2(+) and
      CD4(+)-IL-4(+) cells in the LCLN and spleen were detected by fluorescence
      activated cell sorting. RESULTS: Expression levels of CD4(+), IL-2, and IL-4
      first increased then decreased in LCLN and spleen and peaked 5 and 7 days,
      respectively, after the manifestation of facial paralysis. All the data at the
      peak points were significantly different compared with control (p < 0.05), and
      these effects were inhibited by MPSS. CONCLUSION: Our results suggest that
      CD4(+), IL-2, and IL-4 participate in the HSV-1-induced facial paralysis immune
      response. MPSS can effectively attenuate HSV-1-mediated nervous system damage,
      which is associated with its inhibitory effect on expression of these
      inflammatory markers.

PMID- 24281731
TI  - Synthesis of polydopamine-coated magnetic graphene for Cu(2+) immobilization and
      application to the enrichment of low-concentration peptides for mass spectrometry
      analysis.
AB  - In this work, Cu(2+)-immobilized magnetic graphene@polydopamine (magG@PDA@Cu(2+))
      composites were synthesized for the first time. Magnetic graphene prepared via a
      hydrothermal reaction were easily encapsulated by a layer of polydopamine through
      the oxidative polymerization of dopamine in alkaline buffer, and it was
      conveniently modified with Cu(2+) ions afterward. The as-prepared magG@PDA@Cu(2+)
      composites were endowed with strong magnetic responsivness, excellent
      dispersibility and biological compatibility. We applied the novel nanocomposites
      to the enrichment and identification of low-concentration standard peptides,
      peptides in standard protein digestions, endogenous peptides in human urine and
      serum. The enriched peptides were eluted and analyzed by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      magG@PDA@Cu(2+) composites were proved to exhibit great affinity to both
      hydrophobic and hydrophilic peptides, thus providing a rapid and facile approach
      to the extraction of low-concentration peptides. Notably, peptides at an
      extremely low concentration of 10 pM could be detected by MALDI-TOF MS after
      enrichment with magG@PDA@Cu(2+) composites. The results demonstrated that the
      magG@PDA@Cu(2+) composite is a promising candidate for the enrichment of low
      abundance peptides for mass spectrometry analysis. 

PMID- 24281730
TI  - Wheal and flare reactions in skin prick tests of patients treated with
      montelukast alone or in combination with antihistamines.
AB  - BACKGROUND: Because antileukotrienes may inhibit inflammation, it is plausible
      that montelukast administered for a long time could suppress skin wheal and flare
      reaction, and thus, it should be discarded prior to the tests. This study
      assessed the effect of long-lasting treatment with montelukast alone or in
      combination with antihistamines on wheal and flare in skin pricks tests (SPT) in
      patients sensitized to perennial allergens. METHODS: We conducted a 32-week,
      double-blind, placebo-controlled, cross-over and randomized trial that implicated
      two arms: arm A, 20 patients received levocetirizine, montelukast with or without
      levocetirizine or placebo; arm B, 20 patients received desloratadine, montelukast
      with or without desloratadine or placebo. All treatment periods lasted 6 weeks
      and were separated by 2-week washouts. At baseline and on the last day of each
      treatment period, SPT were performed in all participants. RESULTS: Both
      levocetirizine and desloratadine in monotherapy, or in combination with
      montelukast, were effective in reducing wheal and flare in SPT. Monotherapy with
      montelukast did not change the size of the wheal for either histamine or for
      house dust mites, in either arm of the study, but significantly reduced the size
      of flare for histamine in arm A. Addition of montelukast to antihistamine did not
      exceed efficacy of monotherapy with antihistamine in both arms of the study.
      CONCLUSIONS: Since the size of wheal determines the results of SPT, montelukast,
      even taken for a long time, does not have to be discarded prior to the tests.

PMID- 24281732
TI  - The diversity and functions of choline sulphatases in microorganisms.
AB  - Choline sulphates have two putative roles in microorganisms: as a reservoir of C,
      N and S and as osmoprotectants. Although there is no established connection to
      date regarding the relative distribution of these two functions in microbial
      communities, this information is crucial in determining the role of choline
      sulphate in soils, particularly in cultivated soils where S is limiting.
      Therefore, in order to establish such a connection, the diversity of choline
      sulphatase (betC) genes was investigated in this study using numerous fully
      sequenced microbes available in GenBank. Our genomic analyses revealed
      unequivocally that the betICBA operon is restricted to Rhizobiaceae family
      members, which live under symbiotic conditions that prevent elemental depletion.
      Together with the uniform genetic organisation of the betICBA operon in
      Rhizobiaceae, BetC appears to be both utilised for osmoprotection or S
      replenishment. In contrast, betC in a wide variety of free-living microbes
      (including fungi, archaea and bacteria) was found in a cassette encoding only
      BetC and a choline sulphate transporter, a configuration that appears to be
      responsible for fulfilling elemental S requirements. Lastly, the relatively high
      number of BetC sequences available allowed the identification of a specific
      signature sequence that discriminates between these two functions and also
      globally defines some conserved motifs in microbial choline sulphatases. Due to
      the widespread presence of BetC in microbes and the wide repartition of the betC
      cassette system, the potential importance of choline sulphatase in global S
      recycling requires further clarification. 

PMID- 24281733
TI  - Mixed-species biofilms cultured from an oil sand tailings pond can biomineralize
      metals.
AB  - Here, we used an in vitro biofilm approach to study metal resistance and/or
      tolerance of mixed-species biofilms grown from an oil sand tailings pond in
      northern Alberta, Canada. Metals can be inhibitory to microbial hydrocarbon
      degradation. If microorganisms are exposed to metal concentrations above their
      resistance levels, metabolic activities and hydrocarbon degradation can be slowed
      significantly, if not inhibited completely. For this reason, bioremediation
      strategies may be most effective if metal-resistant microorganisms are used.
      Viability was measured after exposure to a range of concentrations of ions of Cu,
      Ag, Pb, Ni, Zn, V, Cr, and Sr. Mixed-species biofilms were found to be extremely
      metal resistant; up to 20 mg/L of Pb, 16 mg/L of Zn, 1,000 mg/L of Sr, and 3.2
      mg/L of Ni. Metal mineralization was observed by visualization with scanning
      electron microscopy with metal crystals of Cu, Ag, Pb, and Sr exuding from the
      biofilms. Following metal exposure, the mixed-species biofilms were analyzed by
      molecular methods and were found to maintain high levels of species complexity. A
      single species isolated from the community (Rhodococcus erythropolis) was used as
      a comparison against the mixed-community biofilm and was seen to be much less
      tolerant to metal stress than the community and did not biomineralize the metals.

PMID- 24281734
TI  - Sphingobacterium pakistanensis sp. nov., a novel plant growth promoting
      rhizobacteria isolated from rhizosphere of Vigna mungo.
AB  - The taxonomic status of a bacterium, strain NCCP-246(T), isolated from
      rhizosphere of Vigna mungo, was determined using a polyphasic taxonomic approach.
      The strain NCCP-246(T) can grow at 16-37  degrees C (optimum 32  degrees C), at
      pH ranges of 6-8 (optimum growth occurs at pH 7) and in 0-4 % (w/v) NaCl.
      Phylogenetic analysis based upon on 16S rRNA gene sequence comparison revealed
      that strain NCCP-246(T) belonged to genus Sphingobacterium. Strain NCCP-246(T)
      showed highest similarity to the type strain of Sphingobacterium canadense
      CR11(T) (97.67 %) and less than 97 % with other species of the genus. The DNA-DNA
      relatedness value of strain NCCP-246(T) with S. canadense CR11(T) and
      Sphingobacterium thalpophilum JCM 21153(T) was 55 and 44.4 %, respectively. The
      chemotaxonomic data revealed the major menaquinone as MK-7 and dominant cellular
      fatty acids were summed feature 3 [C16:1 omega7c/C16:1 omega6c] (37.07 %), iso
      C15:0 (28.03 %), C16:0 (11.85 %), C17:0 cyclo (8.84 %) and C14:0 (2.42 %). The
      G+C content of the strain was 39.2 mol%. On the basis of DNA-DNA hybridization,
      phylogenetic analyses, physiological and, biochemical data, strain NCCP-246(T)
      can be differentiated from the validly named members of genus Sphingobacterium
      and thus represents as a new species, for which the name, Sphingobacterium
      pakistanensis sp. nov. is proposed with the type strain NCCP-246(T) (= JCM18974
      (T) = KCTC 23914(T)).

PMID- 24281735
TI  - Corynebacterium ulcerans isolates from humans and dogs: fibrinogen, fibronectin
      and collagen-binding, antimicrobial and PFGE profiles.
AB  - Corynebacterium ulcerans has been increasingly isolated as an emerging zoonotic
      agent of diphtheria and other infections from companion animals. Since pets are
      able to act as symptomless carriers, it is also essential to identify virulence
      potential for humans of these isolates. In this work the ability of C. ulcerans
      to bind to fibrinogen (Fbg), fibronectin (Fn) and Type I collagen as well the
      genetic relationship among strains isolated from human and asymptomatic dogs in
      Rio de Janeiro (Brazil) were analyzed. Five pulsed-field gel electrophoresis
      (PFGE) profiles were demonstrated (I, II, III, IV and V). In addition, the IV and
      V profiles exhibiting >=85 % similarity were expressed by the BR-AD41 and BR-AD61
      strains from companion dogs living in the same neighborhood. Independent of the
      PFGE-types, human and dog isolates showed affinity to Fbg, Fn and collagen.
      Heterogeneity of PFGE profiles indicated endemicity of C. ulcerans in the Rio de
      Janeiro metropolitan area. Differences in the expression of adhesins to the human
      extracellular matrix may contribute to variations in the virulence and zoonotic
      potential of C. ulcerans strains. 

PMID- 24281736
TI  - Bacterial quorum sensing: circuits and applications.
AB  - Bacterial quorum sensing (QS) systems are cell density-dependent regulatory
      networks that coordinate bacterial behavioural changes from single cellular
      organisms at low cell densities to multicellular types when their population
      density reaches a threshold level. At this stage, bacteria produce and perceive
      small diffusible signal molecules, termed autoinducers in order to mediate gene
      expression. This often results in phenotypic shifts, like planktonic to biofilm
      or non-virulent to virulent. In this way, they regulate varied physiological
      processes by adjusting gene expression in concert with their population size. In
      this review we give a synopsis of QS mediated cell-cell communication in
      bacteria. The first part focuses on QS circuits of some Gram-negative and Gram
      positive bacteria. Thereafter, attention is drawn on the recent applications of
      QS in development of synthetic biology modules, for studying the principles of
      pattern formation, engineering bi-directional communication system and building
      artificial communication networks. Further, the role of QS in solving the problem
      of biofouling is also discussed. 

PMID- 24281737
TI  - Quantum confinement controlled solar hydrogen production from hydrogen sulfide
      using a highly stable CdS(0.5)Se(0.5)/CdSe quantum dot-glass nanosystem.
AB  - We have demonstrated unique CdS0.5Se0.5 and CdSe quantum dot-glass nanosystems
      with quantum confinement effect. The stable, monodispersed CdS0.5Se0.5 and CdSe
      quantum dots (QDs) of size 2 to 12 nm have been grown in a germanate glass matrix
      by a simple melt quench technique at moderate temperature. XRD and Raman studies
      show formation of hexagonal CdS0.5Se0.5 and CdSe in the glass matrix. The quantum
      confinement of CdS0.5Se0.5 and CdSe was studied using TEM and UV-Vis
      spectroscopy. The band gap of the glass nanosystem was tuned from 3.6 to 1.8 eV
      by controlling the CdS0.5Se0.5 quantum dot size in the glass matrix. It can be
      further tuned to 1.68 eV using growth of CdSe quantum dots in the glass matrix.
      Considering the tuneable band gap of the CdS0.5Se0.5 and CdSe quantum dot-glass
      nanosystem for the visible light absorption, a study of size tuneable
      photocatalytic activity for hydrogen generation from hydrogen sulfide splitting
      was performed under visible light irradiation for the first time. The utmost
      hydrogen evolution, i.e. 8164.53 and 7257.36 MUmol h(-1) g(-1) was obtained for
      the CdS0.5Se0.5 and CdSe quantum dot-glass nanosystems, respectively. The
      apparent quantum yield (AQY) was observed to be 26% and 21% for the CdS0.5Se0.5
      and CdSe quantum dot-glass nanosystems, respectively. It is noteworthy that the
      present glass nanosystem as a photocatalyst was found to be very stable as
      compared to naked powder photocatalysts. 

PMID- 24281738
TI  - Nanostructured singlet fission photovoltaics subject to triplet-charge
      annihilation.
AB  - Singlet exciton fission is an efficient multiple-exciton generation process that
      is vulnerable to a characteristic loss process: triplet-charge annihilation. This
      loss process is characterized in singlet-fission photovoltaics and losses as high
      as 40% are observed in poorly designed devices. Techniques are demonstrated to
      improve charge extraction and reduce triplet-charge annihilation to negligible
      levels at short-circuit conditions. 

PMID- 24281739
TI  - Is the gene-environment interaction paradigm relevant to genome-wide studies? The
      case of education and body mass index.
AB  - This study uses data from the Framingham Heart Study to examine the relevance of
      the gene-environment interaction paradigm for genome-wide association studies
      (GWAS). We use completed college education as our environmental measure and
      estimate the interactive effect of genotype and education on body mass index
      (BMI) using 260,402 single-nucleotide polymorphisms (SNPs). Our results highlight
      the sensitivity of parameter estimates obtained from GWAS models and the
      difficulty of framing genome-wide results using the existing gene-environment
      interaction typology. We argue that SNP-environment interactions across the human
      genome are not likely to provide consistent evidence regarding genetic influences
      on health that differ by environment. Nevertheless, genome-wide data contain rich
      information about individual respondents, and we demonstrate the utility of this
      type of data. We highlight the fact that GWAS is just one use of genome-wide
      data, and we encourage demographers to develop methods that incorporate this vast
      amount of information from respondents into their analyses. 

PMID- 24281740
TI  - Cumulative childhood adversity, educational attainment, and active life
      expectancy among U.S. adults.
AB  - Studies of the early-life origins of adult physical functioning and mortality
      have found that childhood health and socioeconomic context are important
      predictors, often irrespective of adult experiences. However, these studies have
      generally assessed functioning and mortality as distinct processes and used cross
      sectional prevalence estimates that neglect the interplay of disability
      incidence, recovery, and mortality. Here, we examine whether early-life
      disadvantages both shorten lives and increase the number and fraction of years
      lived with functional impairment. We also examine the degree to which educational
      attainment mediates and moderates the health consequences of early-life
      disadvantages. Using the 1998-2008 Health and Retirement Study, we examine these
      questions for non-Hispanic whites and blacks aged 50-100 years using multistate
      life tables. Within levels of educational attainment, adults from disadvantaged
      childhoods lived fewer total and active years, and spent a greater portion of
      life impaired compared with adults from advantaged childhoods. Higher levels of
      education did not ameliorate the health consequences of disadvantaged childhoods.
      However, because education had a larger impact on health than did childhood
      socioeconomic context, adults from disadvantaged childhoods who achieved high
      education levels often had total and active life expectancies that were similar
      to or better than those of adults from advantaged childhoods who achieved low
      education levels. 

PMID- 24281742
TI  - Definition versus measurement of mental pain: a reply to Meerwijk and Weiss.

PMID- 24281744
TI  - CT perfusion and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage:
      a systematic review and meta-analysis.
AB  - Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem,
      and can only be confirmed with follow-up imaging. For treatment of DCI a
      diagnostic tool is needed. We performed a systematic review to evaluate the value
      of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed,
      Embase, and Cochrane databases to identify studies on the relationship between
      CTP and DCI. Eleven studies totaling 570 patients were included. On admission,
      cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT),
      and time-to-peak (TTP) did not differ between patients who did and did not
      develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage
      (SAH)), DCI was associated with a decreased CBF (pooled mean difference -11.9
      mL/100 g per minute (95% confidence interval (CI): -15.2 to -8.6)) and an
      increased MTT (pooled mean difference 1.5 seconds (0.9-2.2)). Cerebral blood
      volume did not differ and TTP was rarely reported. Perfusion thresholds reported
      in studies were comparable, although the corresponding test characteristics were
      moderate and differed between studies. We conclude that CTP can be used in the
      diagnosis but not in the prediction of DCI. A need exists to standardize the
      method for measuring perfusion with CTP after SAH, and optimize and validate
      perfusion thresholds. 

PMID- 24281745
TI  - Cannabis withdrawal syndrome: An important diagnostic consideration in
      adolescents presenting with disordered eating.
AB  - Although previously thought to have no withdrawal symptoms, there is now
      convergent evidence for a cannabis withdrawal syndrome (CWS), criteria for its
      diagnosis, and evidence of its impact in the adolescent population. Cannabis
      withdrawal syndrome represents an important and under-recognized consideration in
      adolescents with disordered eating. We describe three clinical cases of
      adolescents presenting to an eating disorders program with primary complaints of
      gastrointestinal symptoms, food avoidance, and associated weight loss. They did
      not meet the criteria for an eating disorder, but did fulfill the DSM-5 criteria
      for CWS. This report emphasizes the importance of considering the impact of heavy
      cannabis use in adolescents presenting with gastrointestinal complaints, and
      eating disorder symptoms, including weight loss.

PMID- 24281746
TI  - Application of internal electrodes to the oesophageal and tracheal tube in an
      animal trial: evaluation of its clinical and technical potentiality in electrical
      impedance tomography.
AB  - Electrical impedance tomography (EIT) is of potential medical interest e.g., to
      optimize ventilator settings during mechanical ventilation. Nevertheless there
      are still several challenges. Although electrode belts are commonly used and
      promoted, they are not necessarily adequate for the long-term monitoring of
      patients in intensive-care units (ICU). ICU patients are usually equipped with
      breathing tubes and feeding tubes, ideal surfaces to attach EIT electrodes to.
      The aim of our study was therefore to examine the potentiality of internal
      electrodes in a porcine animal trial. Following an animal trial protocol studying
      acute lung injury, additional EIT measurements were obtained both with
      conventional electrodes set upon a rubber belt and after having moved the
      electrodes internally in seven pigs. For this reason the two most dorsally
      located electrodes were selected. An adjacent stimulation and measurement pattern
      was used, and resulting voltages in the time and frequency domains as well as
      within reconstructed images were examined to compare perfusion and ventilation
      data qualitatively and quantitatively. Particularly, lung morphology as well as
      signal strength for both the mediastinal and lung region were studied. All
      animals were submitted to the additional protocol without any adverse events.
      Distinguishability of lungs was improved in reconstructed frames. The resulting
      sensitivity of measured electrical impedance was enhanced around the mediastinal
      region and even cardiac-related activity was significantly increased by a factor
      of up to 6. In conclusion the application of internal electrodes appears to be
      beneficial for diverse clinical purposes and should be addressed in further
      studies. 

PMID- 24281747
TI  - Effects of dietary supplementation of red ginseng marc and alpha-tocopherol on
      the growth performance and meat quality of broiler chicken.
AB  - BACKGROUND: This study aimed to determine the effect of supplementation of
      broiler diets with red ginseng marc and alpha-tocopherol on the growth
      performance and meat quality during a 35-day feeding period. A total of 225
      Hubbard male broiler chicks were fed diets supplemented with 0%, 1%, 2% and 3%
      red ginseng marc, or 2% red ginseng marc + 200 IU alpha-tocopherol kg(-1) and
      randomly allocated to five dietary groups (15 floor pens), so that each group had
      three replicates and 15 broilers per pen (0.09 m(2) per bird). RESULTS: There
      were no differences among the treated groups with regard to growth performance
      and proximate composition, except for mortality and crude fat in broilers. Serum
      cholesterol levels were lower in the chickens receiving diets supplemented with
      red ginseng marc and alpha-tocopherol than those in the control. With the
      exception of water-holding capacity or shear force values, increasing levels of
      red ginseng marc and a combination of red ginseng marc and alpha-tocopherol
      affected chicken thigh meat quality by decreasing the pH and thiobarbituric acid
      reactive substance and increasing the total phenol and DPPH-radical scavenging
      compared with those in the control. Broiler diets with increasing levels of red
      ginseng marc and the combination of red ginseng marc and alpha-tocopherol did not
      affect the color of thigh muscle, but the treatment significantly increased a*
      values. CONCLUSION: Supplementation of poultry diets with 3% red ginseng marc
      markedly reduced mortality and serum cholesterol levels and remarkably improved
      meat quality in broilers.

PMID- 24281743
TI  - Hemorrhagic transformation after ischemic stroke in animals and humans.
AB  - Hemorrhagic transformation (HT) is a common complication of ischemic stroke that
      is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and
      treat HT are needed. In this review, we summarize studies of HT in both animals
      and humans. We propose that early HT (<18 to 24 hours after stroke onset) relates
      to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2
      that damage the neurovascular unit and promote blood-brain barrier (BBB)
      disruption. This contrasts to delayed HT (>18 to 24 hours after stroke) that
      relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and
      endogenous tissue plasminogen activator), neuroinflammation, and factors that
      promote vascular remodeling (vascular endothelial growth factor and high-moblity
      group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed,
      including transforming growth factor beta signaling in monocytes, Src kinase
      signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally,
      clinical features associated with HT in patients with stroke are reviewed,
      including approaches to predict HT by clinical factors, brain imaging, and blood
      biomarkers. Though remarkable advances in our understanding of HT have been made,
      additional efforts are needed to translate these discoveries to the clinic and
      reduce the impact of HT on patients with ischemic stroke. 

PMID- 24281748
TI  - Trachoma prevalence in Niger: results of 31 district-level surveys.
AB  - BACKGROUND: The leading cause of preventable blindness worldwide is trachoma, a
      condition caused by an infection of the inner eyelid. In Niger, a landlocked
      republic in Western Africa, surveys in 1988-89 identified trachoma as endemic in
      all but one region and, as a result, there is a National Prevention of Blindness
      Program plan to eliminate trachoma by 2015. METHODS: Thirty-one districts in
      eastern and western Niger were surveyed for trachoma prevalence from May 2009 to
      March 2012 as part of routine program impact evaluations. Prevalence surveys were
      implemented independently in each district using a two-stage cluster random
      design. Probability proportional to size was used to randomly select villages and
      25 households were selected in each cluster. The prevalence of trachoma of
      clinical grade trachomatous follicular (TF) was estimated in children aged 1-9
      years, and the prevalence of blinding trachoma, trachomatous trichiasis (TT), was
      measured in adults aged >=15 years. RESULTS: A total of 14 211 households was
      surveyed; 58 617 individuals were evaluated for clinical signs of trachoma, of
      whom 27 087 were children aged 1-9 years. District-wide implementation of the
      full SAFE strategy is warranted in 16 districts where TF prevalence exceeds 10%
      and targeted implementation of the SAFE strategy (surgery for trichiasis;
      antibiotic therapy to control transmission; facial cleanliness for hygiene
      promotion; environmental change for improvements in access to water and
      sanitation) is recommended in the remaining 15 districts. The prevalence of TT
      among adults exceeded 1% in nine districts, suggesting that surgical services to
      treat TT should be implemented district-wide. CONCLUSIONS: These results
      establish the need for continued SAFE strategy implementation throughout Niger.

PMID- 24281750
TI  - Hierarchical synthesis of Mo-Sn oxide cage-bell hybrid structures with superior
      lithium storage.
AB  - A facile generic solvothermal alcoholysis strategy is employed to prepare Mo-Sn
      oxide cage-bell hybrid nanoparticle aggregates. The intrinsic hollow core-shell
      nature as well as the multi-element characteristics of active components of the
      unique nanostructures contribute greatly to the enhanced performance as anode
      materials for lithium ion batteries. 

PMID- 24281749
TI  - Recent trends in product development and regulatory issues on impurities in
      active pharmaceutical ingredient (API) and drug products. Part 1: Predicting
      degradation related impurities and impurity considerations for pharmaceutical
      dosage forms.

PMID- 24281751
TI  - Panoscopic organization of anisotropic colloidal structures from photofunctional
      inorganic nanosheet liquid crystals.
AB  - Colloidal liquid crystals of inorganic nanosheets with thickness of around 1 nm
      and lateral dimensions of several micrometers prepared by exfoliation of a
      layered niobate are converted to hierarchically organized arrays whose structures
      are controlled from the nano to macroscopic length scale through the growth of
      liquid crystalline domains called tactoids as the secondary building blocks
      followed by controlled application of external fields. Growth of the tactoids is
      attained by incubation of the liquid crystals at room temperature. The tactoids
      are then assembled into higher-order structures with characteristic lengths of
      sub-mm to mm under the simultaneous application of an ac electric field and
      gravity, whose directions determine the final textural motif of the arrays.
      Whereas a net-like texture is observed when applying the electric and
      gravitational forces in the same direction, a striped texture where the
      nanosheets are unidirectionally aligned is observed when the electric field is
      applied in the direction perpendicular to gravity. The use of well-grown tactoids
      is key to the macroscopic structural control. Since the niobate nanosheets have
      wide band-gap semiconducting nature, the nanosheet stripe arrays exhibit
      photocatalysis that reflected the alignment of the nanosheets with respect to the
      polarized direction of impinging light. 

PMID- 24281752
TI  - Exclusion probabilities and likelihood ratios with applications to kinship
      problems.
AB  - In forensic genetics, DNA profiles are compared in order to make inferences,
      paternity cases being a standard example. The statistical evidence can be
      summarized and reported in several ways. For example, in a paternity case, the
      likelihood ratio (LR) and the probability of not excluding a random man as father
      (RMNE) are two common summary statistics. There has been a long debate on the
      merits of the two statistics, also in the context of DNA mixture interpretation,
      and no general consensus has been reached. In this paper, we show that the RMNE
      is a certain weighted average of inverse likelihood ratios. This is true in any
      forensic context. We show that the likelihood ratio in favor of the correct
      hypothesis is, in expectation, bigger than the reciprocal of the RMNE
      probability. However, with the exception of pathological cases, it is also
      possible to obtain smaller likelihood ratios. We illustrate this result for
      paternity cases. Moreover, some theoretical properties of the likelihood ratio
      for a large class of general pairwise kinship cases, including expected value and
      variance, are derived. The practical implications of the findings are discussed
      and exemplified. 

PMID- 24281753
TI  - The Experience of Cognitive Impairment in People with Psychosis.
AB  - Cognitive impairment has been widely studied in people with psychosis. However,
      research is lacking into the subjective experience of cognitive impairment, its
      impact and ways in which individuals cope. This study aimed to provide an account
      of the experience of cognitive impairment in people with a diagnosis of
      schizophrenia, including what difficulties people experience, how these
      difficulties are understood, how people respond to these difficulties and how
      they perceive others' views of these difficulties. A semi-structured interview
      was carried out with eight participants with a diagnosis of schizophrenia
      focusing on participants' experiences of difficulties with cognitive functioning.
      Interpretative phenomenological analysis was used to analyse interview
      transcripts. Experience of cognitive impairment was understood in terms of six
      master themes: impaired controlled thinking, physical sensations and impaired
      movement, explanations for the impairment and comparisons to the past, managing
      the impairment, how others see the impairment and anticipating the future. This
      study is the first rigorous qualitative study of the subjective experience of
      cognitive impairment in people with psychosis, and it provides greater context
      for empirical findings. The results have significant implications for clinical
      psychology, including education about cognitive difficulties and the importance
      of cognitive functioning to formulation. New areas for research include coping
      strategies in relation to functioning and future perspectives, ascertaining staff
      understanding of cognitive impairment, and reflective conversation style as an
      intervention for metacognitive difficulties. Key Practitioner Message
      Difficulties with cognitive functioning should be considered in clinical
      practitioners' formulations of clients' difficulties in the context of psychosis.
      Services should consider providing service user and carer education about
      cognitive impairment in psychosis. Staff may need further training in order to
      support people with psychosis who have difficulties with cognitive functioning.

PMID- 24281754
TI  - Prospective 'real world' registry for the use of the 'PCB only' strategy in small
      vessel de novo lesions.
AB  - BACKGROUND: This prospective registry assessed the safety and efficacy of
      paclitaxel coated balloon (PCB) angioplasty for small vessel coronary artery
      disease in Europe and Asia with the intention to treat lesions without additional
      stenting. The use of PCBs in small vessels seems to be associated with favourable
      outcomes; however, prospective data for the use of PCBs without stenting are
      limited. METHODS: The SeQuent Please Small Vessel 'PCB only' Registry was an
      international, prospective, multicentre registry enrolling patients with de novo
      lesions of small reference diameters (>= 2.0 mm, <= 2.75 mm). The primary end
      point was clinically driven target lesion revascularisation (TLR) at 9 months.
      Secondary end points were acute technical success, in-hospital outcomes, 9-month
      major adverse cardiac events (MACE) (death, myocardial infarction, or TLR), and
      the occurrence of definite lesion and vessel thrombosis. RESULTS: A total of 479
      patients (66.1 +/- 10.9 years, 36.7% diabetics) were enrolled, 105 (23.5%) with
      an acute coronary syndrome, 41 (9.2%) with ST elevation myocardial infarction
      (STEMI), and 60 (14.8%) with non-STEMI. The initial procedural success rate was
      99.0%; 27 patients (6%) needed additional bare metal stent implantation. TLR at
      9.4+/-1.7 months occurred in 14 patients (3.6%), while three patients (0.6%) had
      vessel thrombosis in non-target lesions. There was no cardiac death or coronary
      artery bypass graft surgery. CONCLUSIONS: To date, this is the largest
      prospective study with PCBs in small vessel de novo lesions in unselected
      patients. Rates of TLR and MACE were low, suggesting the use of PCBs may be an
      attractive alternative treatment option to drug eluting stents in small vessels.

PMID- 24281755
TI  - Palpitations in a 64-year-old man.
AB  - A 64-year-old man presented with several weeks of intermittent irregular
      palpitations. He had no prior history of cardiac disease, hypertension or
      syncope. A 12-lead ECG revealed sinus rhythm with premature atrial and
      ventricular contractions and high QRS voltages consistent with LV-hypertrophy.
      Cardiac MR revealed asymmetrical septal hypertrophy and marked mid-myocardial
      hyperenhancement of the interventricular septum. 

PMID- 24281756
TI  - Taxonomic re-evaluation of black koji molds.
AB  - Black koji molds including its albino mutant, the white koji mold, have been
      widely used for making the distilled spirit shochu in Northeast Asia because they
      produce citric acid which prevents undesirable contamination from bacteria. Since
      Inui reported Aspergillus luchuensis from black koji in Okinawa in 1901, many
      fungal names associated with black koji molds were reported. However, some
      species are similar and differentiation between species is difficult. Fungal
      taxonomists tried to arrange a taxonomic system for black koji molds, but the
      results were not clear. Recently, multi-locus sequence typing has been
      successfully used to taxonomy of black Aspergillus. According to beta-tubulin and
      calmodulin gene sequences, black koji molds can be subdivided in three species,
      A. luchuensis, Aspergillus niger, and Aspergillus tubingensis. Aspergillus
      awamori, Aspergillus kawachii, Aspergillus inuii, Aspergillus nakazawai, and
      Aspergillus coreanus are synonyms of A. luchuensis, Aspergillus batatae,
      Aspergillus aureus (or Aspergillus foetidus), Aspergillus miyakoensis, and
      Aspergillus usamii (including A. usamii mut. shirousamii) are synonyms of A.
      niger and Aspergillus saitoi and A. saitoi var. kagoshimaensis are synonyms of A.
      tubingensis. A. luchuensis mut. kawachii was suggested particular names for A.
      kawachii because of their industrial importance. The history and modern taxonomy
      of black koji molds is further discussed. 

PMID- 24281757
TI  - 2-methylbutanal, a volatile biomarker, for non-invasive surveillance of Proteus.
AB  - Pathogen detection needs a paradigm shift from time-consuming conventional
      microbiological and biochemical tests to much simpler identification methods with
      higher sensitivity and specificity. In this regard, a simple detection method for
      frequently isolated nosocomial uropathogen, Proteus spp., was developed using the
      characteristic volatile 2-methylbutanal released in Luria Bertani broth. The
      instant reaction of the compound with 5-dimethylaminonaphthalene-1
      sulfonylhydrazine (DNSH) has been adapted to develop a sensitive fluorescence
      assay named "ProteAl" (Prote, "Proteus" & Al, "Aldehyde"). The assay was
      performed by direct addition of the fluorescence reagent to the culture after 7 h
      of growth. The distinct green fluorescence by Proteus (other organisms show
      orange fluorescence) served as the simplest and quicker identification test
      available for Proteus. In the laboratory, it exhibited 100% specificity and 100%
      sensitivity during testing of 95 strains including standard and known clinical
      isolates representing frequently encountered uropathogens.

PMID- 24281758
TI  - Modulating enzyme activity using ionic liquids or surfactants.
AB  - One of the important strategies for modulating enzyme activity is the use of
      additives to affect their microenvironment and subsequently make them suitable
      for use in different industrial processes. Ionic liquids (ILs) have been
      investigated extensively in recent years as such additives. They are a class of
      solvents with peculiar properties and a "green" reputation in comparison to
      classical organic solvents. ILs as co-solvents in aqueous systems have an effect
      on substrate solubility, enzyme structure and on enzyme-water interactions. These
      effects can lead to higher reaction yields, improved selectivity, and changes in
      substrate specificity, and thus there is great potential for IL incorporation in
      biocatalysis. The use of surfactants, which are usually denaturating agents, as
      additives in enzymatic reactions is less reviewed in recent years. However,
      interesting modulations in enzyme activity in their presence have been reported.
      In the case of surfactants there is a more pronounced effect on the enzyme
      structure, as can be observed in a number of crystal structures obtained in their
      presence. For each additive and enzymatic process, a specific optimization
      process is needed and there is no one-fits-all solution. Combining ILs and
      surfactants in either mixed micelles or water-in-IL microemulsions for use in
      enzymatic reaction systems is a promising direction which may further expand the
      range of enzyme applications in industrial processes. While many reviews exist on
      the use of ILs in biocatalysis, the present review centers on systems in which
      ILs or surfactants were able to modulate and improve the natural activity of
      enzymes in aqueous systems. 

PMID- 24281759
TI  - Ray-casting based evaluation framework for haptic force feedback during
      percutaneous transhepatic catheter drainage punctures.
AB  - PURPOSE: Development of new needle insertion force feedback algorithms requires
      comparison with a gold standard method. A new evaluation framework was formulated
      and tested on needle punctures for percutaneous transhepatic catheter drainage
      (PTCD). METHODS: Needle insertion is an established procedure for minimally
      invasive interventions in the liver. Up-to-date, needle insertions are precisely
      planned using 2D axial CT slices from 3D data sets. To provide a 3D virtual
      reality and haptic training and planning environment, the full segmentation of
      patient data is often a mandatory step. To lessen the time required for manual
      segmentation, we propose direct haptic volume-rendering based on CT gray values
      and partially segmented patient data. The core contribution is a new force output
      evaluation method driven by a ray-casting technique that defines paths from the
      skin to target structures, i.e., the right hepatic duct near the juncture with
      the common hepatic duct. A ray-casting method computes insertion trajectories
      from the skin to the duct considering no-go structures and plausibility criteria.
      A rating system scores each trajectory. Finally, the best insertion trajectories
      are selected that reach the target. Along the selected paths, force output
      comparison between a reference system and the new haptic force output algorithm
      is carried out, quantified and visualized. RESULTS: The evaluation framework is
      presented along with an exemplary study of the liver using the atlas data set
      from a reference patient. In a comparison of our reference method to a newer
      algorithm, force outputs are found to be similar in 99% of the paths. CONCLUSION:
      The proposed evaluation framework allows reliable detection of problematic PTCD
      trajectories and provides valuable hints to improve force feedback algorithm
      development.

PMID- 24281760
TI  - Effects of soil tillage on Tuber magnatum development in natural truffieres.
AB  - Tuber magnatum Pico, the Italian white truffle, commands the highest prices of
      any truffle. Despite its commercial value, it is the only edible European truffle
      which has not yet been successfully cultivated. Because of this, it is essential
      to safeguard natural truffieres and to identify cultural practices to maximize
      their productivity. Soil tillage is successfully and extensively used in black
      truffle cultivation to enhance productivity, but its effects are not known on the
      development of T. magnatum. A recently developed real-time PCR assay was applied
      to evaluate the effects of tillage (10-15 cm depth) on T. magnatum mycelium in
      two different natural truffle grounds located in Tuscany and Emilia-Romagna.
      Tillage effects on bulk density, ectomycorrhizal fungal communities, and ascoma
      production were also assessed. Tilling significantly increased the quantity of T.
      magnatum mycelium which seemed to be related to an increase in soil porosity by
      up to 34%, and the diversity of ectomycorrhizal fungal communities. On the
      contrary, no significant effects were found on ascoma production. The results
      highlight that real-time PCR is the most reliable method for evaluating the
      effects of cultural practices on the development of T. magnatum in soil avoiding
      long-term studies on fruiting body production.

PMID- 24281761
TI  - Time-resolved analysis of the matrix metalloproteinase 10 substrate degradome.
AB  - Proteolysis is an irreversible post-translational modification that affects intra
      and intercellular communication by modulating the activity of bioactive
      mediators. Key to understanding protease function is the system-wide
      identification of cleavage events and their dynamics in physiological contexts.
      Despite recent advances in mass spectrometry-based proteomics for high-throughput
      substrate screening, current approaches suffer from high false positive rates and
      only capture single states of protease activity. Here, we present a workflow
      based on multiplexed terminal amine isotopic labeling of substrates for time
      resolved substrate degradomics in complex proteomes. This approach significantly
      enhances confidence in substrate identification and categorizes cleavage events
      by specificity and structural accessibility of the cleavage site. We demonstrate
      concomitant quantification of cleavage site spanning peptides and neo-N and/or
      neo-C termini to estimate relative ratios of noncleaved and cleaved forms of
      substrate proteins. By applying this strategy to dissect the matrix
      metalloproteinase 10 (MMP10) substrate degradome in fibroblast secretomes, we
      identified the extracellular matrix protein ADAMTS-like protein 1 (ADAMTSL1) as a
      direct MMP10 substrate and revealed MMP10-dependent ectodomain shedding of
      platelet-derived growth factor receptor alpha (PDGFRalpha) as well as sequential
      processing of type I collagen. The data have been deposited to the
      ProteomeXchange Consortium with identifier PXD000503. 

PMID- 24281763
TI  - Acute Kidney Injury Due to Interaction of Methyl-1-testosterone with Ciclosporin
      Metabolism in a Patient with Severe Atopic Dermatitis.
AB  - Ciclosporin is widely used in a number of inflammatory disorders and has the
      potential for drug interactions. We report here a case of acute kidney injury due
      to the interaction of ciclosporin with methyl-1-testosterone. This has not been
      previously reported and it is relevant as methyl-1-testosterone can be purchased
      online. Physicians should be aware of any over the counter or online purchased
      "supplements" and consider possible drug interactions. 

PMID- 24281764
TI  - Frontiers in rotational spectroscopy: shapes and tunneling dynamics of the four
      conformers of the acrylic acid--difluoroacetic acid adduct.
AB  - The rotational spectra of four conformers of the acrylic acid-difluoroacetic acid
      adduct (CH2 =CHCOOH-CHF2 COOH, AA-DFA) are reported and information on their
      internal dynamics is supplied. This represents an unprecedented result for the
      conformational analysis, with microwave spectroscopy, of such a heavy molecular
      adduct. 

PMID- 24281765
TI  - Biogenic amines and collective organization in a superorganism: neuromodulation
      of social behavior in ants.
AB  - The ecological dominance of ants has to a great extent been achieved through
      their collective action and complex social organization. Ants provide diverse
      model systems to examine the neural underpinnings of individual behavior and
      group action that contribute to their evolutionary success. Core elements of ant
      colony structure such as reproductive and ergonomic division of labor, task
      specialization, and social integration are beginning to be understood in terms of
      cellular neuroanatomy and neurochemistry. In this review we discuss the
      neuroethology of colony organization by focusing on the role of biogenic amines
      in the control of social behavior in ants. We examine the role of neuromodulation
      in significant sociobiological characteristics of ants, including reproductive
      hierarchies, colony foundation, social food flow, nestmate recognition,
      territoriality, and size- and age-related sensory perception and task performance
      as well as the involvement of monoamines in collective intelligence, the ultimate
      key to the global dominance of these remarkable superorganisms. We conclude by
      suggesting future directions for the analysis of the aminergic regulation of
      behavior and social complexity in ants.

PMID- 24281766
TI  - Adaxial-abaxial polarity: the developmental basis of leaf shape diversity.
AB  - Leaves of flowering plants are diverse in shape. Part of this morphological
      diversity can be attributed to differences in spatiotemporal regulation of
      polarity in the upper (adaxial) and lower (abaxial) sides of developing leaves.
      In a leaf primordium, antagonistic interactions between polarity determinants
      specify the adaxial and abaxial domains in a mutually exclusive manner. The
      patterning of those domains is critical for leaf morphogenesis. In this review,
      we first summarize the gene networks regulating adaxial-abaxial polarity in
      conventional bifacial leaves and then discuss how patterning is modified in
      different leaf type categories.

PMID- 24281762
TI  - Glutamate transporters in the biology of malignant gliomas.
AB  - Malignant gliomas are relentless tumors that offer a dismal clinical prognosis.
      They develop many biological advantages that allow them to grow and survive in
      the unique environment of the brain. The glutamate transporters system x c (-)
      and excitatory amino acid transporters (EAAT) are emerging as key players in the
      biology and malignancy of these tumors. Gliomas manipulate glutamate transporter
      expression and function to alter glutamate homeostasis in the brain, which
      supports their own growth, invasion, and survival. As a consequence, malignant
      cells are able to quickly destroy and invade surrounding normal brain. Recent
      findings are painting a larger picture of these transporters in glioma biology,
      and as such are providing opportunities for clinical intervention for patients.
      This review will detail the current understanding of glutamate transporters in
      the biology of malignant gliomas and highlight some of the unique aspects of
      these tumors that make them so devastating and difficult to treat. 

PMID- 24281767
TI  - Hypospadias and variants in genes related to sex hormone biosynthesis and
      metabolism.
AB  - We examined whether variants in genes related to sex hormone biosynthesis and
      metabolism were associated with hypospadias in humans. We examined 332 relatively
      common tag single-nucleotide polymorphisms (tagSNPs) in 20 genes. Analyses
      included 633 cases (84 mild, 322 moderate, 212 severe and 15 undetermined
      severity) and 855 population-based non-malformed male controls born in California
      from 1990 to 2003. We used logistic regression models to estimate odds ratios
      (OR) and 95% confidence intervals (CI) for each SNP. Several of the 332 studied
      SNPs had p < 0.01: one in CYP3A4, four in HSD17B3, one in HSD3B1, two in STARD3,
      10 in SRD5A2 and seven in STS. In addition, haplotype analyses gave several
      associations with p < 0.01. For HSD17B3, 14-SNP and 5-SNP blocks had ORs of 1.5
      (95% CI 1.1, 2.0, p < 0.001) and 2.8 (95% CI 1.6, 4.8, p < 0.001) respectively.
      For SRD5A2, 9-SNP, 3-SNP and 8-SNP blocks had ORs of 1.7 (95% CI 1.3, 2.2, p <
      0.001), 1.4 (95% CI 1.1, 1.8, p = 0.008) and 1.5 (95% CI 1.2, 1.9, p = 0.002)
      respectively. Our study indicates that several genes that contribute to sex
      hormone biosynthesis and metabolism are associated with hypospadias risk. 

PMID- 24281768
TI  - Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line
      treatment of epidermal growth factor receptor-activating mutation-positive non
      small-cell lung cancer patients in Hong Kong.
AB  - OBJECTIVE: To compare the effectiveness and cost-effectiveness of erlotinib
      versus gefitinib as first-line treatment of epidermal growth factor receptor
      activating mutation-positive non-small-cell lung cancer patients. DESIGN.
      Indirect treatment comparison and a cost-effectiveness assessment. SETTING: Hong
      Kong. PATIENTS: Those having epidermal growth factor receptor-activating mutation
      positive non-small-cell lung cancer. INTERVENTIONS: Erlotinib versus gefitinib
      use was compared on the basis of four relevant Asian phase-III randomised
      controlled trials: one for erlotinib (OPTIMAL) and three for gefitinib (IPASS;
      NEJGSG; WJTOG). The cost-effectiveness assessment model simulates the transition
      between the health states: progression-free survival, progression, and death over
      a lifetime horizon. The World Health Organization criterion (incremental cost
      effectiveness ratio <3 times of gross domestic product/capita: <US$102 582;
      approximately <HK$798 078) was used to rate cost-effectiveness. RESULTS: The best
      fit of study characteristics and prognostic patient characteristics were found
      between the OPTIMAL and IPASS trials. Comparing progression-free survival hazard
      ratios of erlotinib versus gefitinib using only these randomised controlled
      trials in an indirect treatment comparison resulted in a statistically
      significant progression-free survival difference in favour of erlotinib (indirect
      treatment comparison hazard ratio=0.33; 95% confidence interval, 0.19-0.58;
      P=0.0001). The cost-effectiveness assessment model showed that the cost per
      progression-free life year gained and per quality-adjusted life year gained was
      at acceptable values of US$39 431 (approximately HK$306 773) and US$62 419
      (approximately HK$485 619) for erlotinib versus gefitinib, respectively.
      CONCLUSION: The indirect treatment comparison of OPTIMAL versus IPASS shows that
      erlotinib is significantly more efficacious than gefitinib. Furthermore, the cost
      effectiveness assessment indicates that the incremental cost-effectiveness ratios
      are well within an acceptable range in relation to the survival benefits
      obtained. In conclusion, erlotinib is cost-effective compared to gefitinib for
      first-line epidermal growth factor receptor-activating mutation-positive non
      small-cell lung cancer patients.

PMID- 24281769
TI  - Prognostic value of podoplanin expression in oral squamous cell carcinoma--a
      regression model auxiliary to UICC classification.
AB  - Podoplanin, a type I transmembrane glycoprotein with an effect of platelet
      aggregation, has been reported to be one of the possible prognostic factors of
      oral squamous cell carcinoma (OSCC). However, the biological significance of
      podoplanin is largely unclear. The aim of this study was to develop a practical
      model for the prediction of prognosis using the grade of podoplanin expression,
      and also to evaluate the biological function of podoplanin. Eighty-two specimens
      of patients with previously untreated OSCC, who underwent either biopsy or
      surgery, were histopathologically and immunohistochemically analyzed. These 82
      cases were composed of 66 well-differentiated, 10 moderately differentiated and 6
      poorly differentiated OSCC. Podoplanin was successfully immunostained in 78
      specimens, and was detected in most cases, but the frequency of positive cells
      varied. The prognosis of patients with more than 50 % podoplanin-positive tumor
      cells was significantly poorer than that of the other patients. Multivariate
      hazards regression analysis suggested that a linear combination of covariates,
      OSCC patients with more or less than 50 % podoplanin expression, age of more or
      less than 70 years old, mode of invasion and T3, T4 or T2 versus T1 of the UICC T
      stage classification was the most effective model for evaluating the prognosis of
      OSCC patients. Additionally, podoplanin expression had a significant relationship
      to UICC clinical stage and the expression of Ki-67. An effective regression model
      using podoplanin expression was developed for evaluating the prognosis of OSCC
      and the biological significance of podoplanin was suggested to be associated with
      the growth and/or progression of OSCC.

PMID- 24281770
TI  - Motivational interviewing promotes adherence and improves wellbeing in pre
      dialysis patients with advanced chronic kidney disease.
AB  - Low rates of adherence to medical treatments and adverse emotional states are a
      widespread problem in advanced chronic kidney disease (ACKD). Motivational
      interviewing using the stages of change model is an effective combination in
      promoting behavior modifications. The objective of the present study was to
      determine the effectiveness of an individual, pre-dialysis intervention program
      (monthly sessions of 90 min over a 6-month period) in terms of adherence,
      emotional state and health-related quality of life (HRQL). Forty-two patients
      were evaluated for adherence, depression, anxiety and HRQL with standardized self
      report questionnaires. Biochemical markers were also registered. The results show
      that after the intervention, patients reported significantly higher levels of
      adherence, lower depression and anxiety levels, and better HRQL (i.e., general
      health and emotional role domains). Biochemical parameters were controlled
      significantly better after the intervention, except for iPTH. These findings
      highlight the potential benefit of applying individual psycho-educational
      intervention programs based on motivational interviewing and using the stages of
      change model to promote adherence and wellbeing in ACKD patients. 

PMID- 24281771
TI  - "Sand-watch" spinal cord: a case of inferior cervical spinal cord atrophy.

PMID- 24281772
TI  - Optimization of computed tomography (CT) arthrography of hip for the
      visualization of cartilage: an in vitro study.
AB  - OBJECTIVE: We sought to optimize the kilovoltage, tube current, and the radiation
      dose of computed tomographic arthrography of the hip joint using in vitro
      methods. MATERIALS AND METHODS: A phantom was prepared using a left femoral head
      harvested from a patient undergoing total hip arthroplasty and packed in a condom
      filled with iodinated contrast. The right hip joint of a cadaver was also
      injected with iodinated contrast. The phantom and the cadaver were scanned using
      different values of peak kilovoltage (kVp) and tube current (milliamp seconds,
      mAs). Three different regions of interest (ROI) were drawn in the cartilage,
      subchondral bone plate, and intraarticular contrast. The attenuation values,
      contrast/noise ratio (CNR), and effective dose were calculated. Two independent
      observers classified the quality of the contrast-cartilage interface and the
      cartilage-subchondral bone plate interface as (1) diagnostic quality or (2)
      nondiagnostic quality. RESULTS: Contrast, cartilage, and subchondral bone plate
      attenuation values decreased at higher kVp. CNR increased with both kVp and mAs.
      The qualitative analysis showed that in both phantom and cadaver, at 120 kVp and
      50 mAs, the contrast-cartilage and cartilage-subchondral bone plate interfaces
      were of diagnostic quality, with an effective dose decreased to 0.5 MSv.
      CONCLUSIONS: The absolute effective dose is not directly related to the quality
      of images but to the specific combination of kVp and mAs used for image
      acquisition. The combination of 120 kVp and 50 mAs can be suggested to decrease
      the dose without adversely affect the visibility of cartilage and subchondral
      bone plate.

PMID- 24281773
TI  - Risk of acetabular protrusion is low in rheumatoid arthritis patients treated
      with bipolar hemiarthroplasty for displaced femoral neck fractures without
      rheumatoid change in hip joints.
AB  - OBJECTIVES: The aim of this study was to analyze the radiological outcomes of
      bipolar hemiarthroplasty after displaced femoral neck fractures of non-arthritic
      hip joints in rheumatoid arthritis patients. METHODS: We retrospectively
      investigated 25 hip joints in 23 rheumatoid arthritis patients who underwent
      bipolar hemiarthroplasty for displaced femoral neck fracture of non-arthritic hip
      joints. All patients were female with an average age of 69.8 years (range 51-83
      years). Mean follow-up duration was 8.4 years (range 5-12 years). Radiographs
      taken immediately, 1 year after surgery and most recently, were collected for
      each case. Radiographic measurement of the migration distance of the outer-head
      prosthesis in the direction of vertical, horizontal and medial to Kohler's line
      was undertaken at 1 year after surgery and most recently. RESULTS: No patients
      had hip-related pain after surgery. No case indicated apparent central migration
      and >3-mm migration of the hemisphere in each direction. There was no significant
      change in migration distance between evaluation at 1 year after surgery and most
      recently. CONCLUSIONS: We conclude that risk of acetabular protrusion appears to
      be low in patients of rheumatoid arthritis treated with bipolar hemiarthroplasty
      for displaced femoral neck fractures of non-arthritic hip joints in the medium
      term.

PMID- 24281774
TI  - Solvent promoted reversible cyclometalation in a tethered NHC iridium complex.
AB  - Reaction of [Ir(COD)(py-I(t)Bu)](+) (py-I(t)Bu = 3-tert-butyl-1-picolylimidazol-2
      ylidene) with acetonitrile results in reversible intramolecular C-H bond
      activation of the NHC ligand and formation of [Ir(eta(2):eta(1)-C8H13)(py
      I(t)Bu')(NCMe)](+). Coordinated COD acts as an internal hydride acceptor and
      acetonitrile coordination offsets the otherwise unfavourable thermodynamics of
      the process. 

PMID- 24281775
TI  - Pancreaticoduodenectomy after bariatric surgery: challenges and available
      techniques for reconstruction.
AB  - INTRODUCTION: Obesity is an epidemic in the U.S.A., with approximately 7% of the
      population considered morbidly obese (BMI > 40 or >35 with significant
      comorbidities). DISCUSSION: Weight loss surgery is recognized as a durable
      solution to both obesity and obesity-associated morbidities. With an increasing
      number of pancreatic lesions being discovered on cross-sectional imaging, the
      pancreatic surgeon is increasingly likely to encounter patients with prior
      bariatric surgery who are in need of pancreaticoduodenectomy. As such, surgeons
      need to be familiar with the various bariatric operations, as well as the manner
      in which to handle prior bariatric reconstructions at the time of pancreatic
      surgery. Literature on this topic, however, is scarce with only a handful of
      small case series. CONCLUSION: We herein review the different operations
      performed for weight loss, as well as provide an overview of the available
      operative approaches for reconstruction after pancreaticoduodenectomy in
      postbariatric surgical patients.

PMID- 24281776
TI  - Management of split-thickness skin graft donor sites: a randomized controlled
      trial of calcium alginate versus polyurethane film dressing.
AB  - BACKGROUND: Split-thickness skin graft (STSG) donor sites sometimes cause more
      postoperative morbidity for patients than the wound covered with the graft. Yet,
      there is no consensus on which dressings are best suited to treat these donor
      sites. OBJECTIVE: To evaluate two commonly used modern wound dressings in the
      postoperative healing of STSG donor sites in a prospective randomized controlled
      trial. METHODS: 38 patients were randomly assigned to treatment of an STSG donor
      site with an alginate dressing or a polyurethane film dressing. The primary
      outcome measures were postoperative pain scores, secondary outcome variables were
      time to epithelialization, dressing changes and complications. RESULTS:
      Postoperative pain on day 1 was significantly lower in the polyurethane film
      group (2.05 vs. 0.79, p = 0.035) as compared to the alginate group. This
      difference was not detected on day 5 (0.89 vs. 0.53, p = 0.52). Time to
      epithelialization did not differ significantly between the two dressing groups.
      There were more dressing changes in the polyurethane film group and problems with
      leakage. CONCLUSION: Whereas film dressings resulted in initially lower pain
      scores, alginate dressings caused fewer additional dressing changes and less
      leakage.

PMID- 24281778
TI  - The copper-free Sonogashira cross-coupling reaction promoted by palladium
      complexes of nitrogen-containing chelating ligands in neat water at room
      temperature.
AB  - The commercially available 2,2'-dipyridylamine was used as a supporting ligand in
      the palladium-catalyzed Sonogashira cross-coupling reaction. The reactions
      between aryl iodides and terminal alkynes with different steric hindrance can be
      efficiently performed in the absence of copper in neat water at room temperature.
      The superior catalytic performance of the catalytic system was attributed to
      water solubility of the palladium 2,2'-dipyridylamine complex. Palladium
      nanoparticles with small size and narrow size distribution were formed after the
      cross-coupling reaction. 

PMID- 24281777
TI  - Different iron sources to study the physiology and biochemistry of iron
      metabolism in marine micro-algae.
AB  - We compared ferric EDTA, ferric citrate and ferrous ascorbate as iron sources to
      study iron metabolism in Ostreococcus tauri, Phaeodactlylum tricornutum and
      Emiliania huxleyi. Ferric EDTA was a better iron source than ferric citrate for
      growth and chlorophyll levels. Direct and indirect experiments showed that iron
      was much more available to the cells when provided as ferric citrate as compared
      to ferric EDTA. As a consequence, growth media with iron concentration in the
      range 1-100 nM were rapidly iron-depleted when ferric citrate-but not ferric EDTA
      was the iron source. When cultured together, P. tricornutum cells overgrew the
      two other species in iron-sufficient conditions, but E. huxleyi was able to
      compete other species in iron-deficient conditions, and when iron was provided as
      ferric citrate instead of ferric EDTA, which points out the critical influence of
      the chemical form of iron on the blooms of some phytoplankton species. The use of
      ferric citrate and ferrous ascorbate allowed us to unravel a kind of regulation
      of iron uptake that was dependent on the day/night cycles and to evidence
      independent uptake systems for ferrous and ferric iron, which can be regulated
      independently and be copper-dependent or independent. The same iron sources also
      allowed one to identify molecular components involved in iron uptake and storage
      in marine micro-algae. Characterizing the mechanisms of iron metabolism in the
      phytoplankton constitutes a big challenge; we show here that the use of iron
      sources more readily available to the cells than ferric EDTA is critical for this
      task. 

PMID- 24281779
TI  - Pharmacogenomic testing and personalized treatment of depression.
AB  - BACKGROUND: There is wide variation in antidepressant efficacy and tolerability
      during the treatment of major depressive disorder, a brain disease associated
      with significant morbidity and mortality risk. The ability to rapidly identify
      optimal treatment, thereby shortening the time to symptomatic remission, could
      reduce these risks and associated costs. CONTENT: Up to 42% of variance in
      antidepressant response is associated with common genetic variation, and there
      are over 10 psychotropic medications for which the US Food and Drug
      Administration-approved labeling reflects a genetic test. Most published studies
      have examined functional variations in genes of the cytochrome p450 system,
      relevant to metabolism of many antidepressants. However, there are few data
      supporting the clinical usefulness of specific pharmacogenetic tests. Randomized
      trials and cost-effectiveness studies are emerging, but larger-scale studies are
      needed. Specific challenges in translating genetic association results to
      clinical practice include need for replication to address risk of type I error,
      overestimation of effect sizes, absence of data from generalizable cohorts, and
      absence of comparative data that would suggest one specific intervention over
      another. Several opportunities to accelerate development and validation of new
      tools for stratification remain, including integration of these tests with
      clinical data or other biomarkers and application of electronic health records
      for test development and investigation. SUMMARY: Although common genetic
      variation, particularly in genes of the cytochrome p450 system, has been
      associated with antidepressant response, evidence that this variation may be
      successfully applied to guide treatment selection is just emerging. Larger-scale
      studies facilitated by informatics tools will clarify the usefulness of such
      tests.

PMID- 24281780
TI  - Calcineurin activity assay measurement by liquid chromatography-tandem mass
      spectrometry in the multiple reaction monitoring mode.
AB  - BACKGROUND: Blood concentrations of the calcineurin inhibitors (CNIs)
      cyclosporine and tacrolimus are currently measured to monitor immunosuppression
      in transplant patients. The measurement of calcineurin (CN) phosphatase activity
      has been proposed as a complementary pharmacodynamic approach. However,
      determining CN activity with current methods is not practical. We developed a new
      method amenable to routine use. METHODS: Using liquid chromatography-multiple
      reaction monitoring mass spectrometry (LC-MRM-MS), we quantified CN activity by
      measuring the dephosphorylation of a synthetic phosphopeptide substrate. A stable
      isotope analog of the product peptide served as internal standard, and a novel
      inhibitor cocktail minimized dephosphorylation by other major serine/threonine
      phosphatases. The assay was used to determine CN activity in peripheral blood
      mononuclear cells (PBMCs) isolated from 20 CNI-treated kidney transplant patients
      and 9 healthy volunteers. RESULTS: Linearity was observed from 0.16 to 2.5
      MUmol/L of product peptide, with accuracy in the 15% tolerance range. Intraassay
      and interassay recoveries were 100.6 (9.6) and 100 (7.5), respectively. Michaelis
      Menten kinetics for purified CN were Km = 10.7 (1.6) MUmol/L, Vmax = 2.8 (0.3)
      MUmol/min . mg, and for Jurkat lysate, Km = 182.2 (118.0) MUmol/L, Vmax = 0.013
      (0.006) MUmol/min . mg. PBMC CN activity was successfully measured in a single
      tube with an inhibitor cocktail. CONCLUSIONS: Because LC-MRM-MS is commonly used
      in routine clinical dosage of drugs, this CN activity assay could be applied,
      with parallel blood drug concentration monitoring, to a large panel of patients
      to reevaluate the validity of PBMC CN activity monitoring.

PMID- 24281781
TI  - State of the art for measurement of urine albumin: comparison of routine
      measurement procedures to isotope dilution tandem mass spectrometry.
AB  - BACKGROUND: Urine albumin is the primary biomarker for detection and monitoring
      of kidney damage. Because fixed decision criteria are used to identify patients
      with increased values, we investigated if commonly used routine measurement
      procedures gave comparable results. METHODS: Results from 17 commercially
      available urine albumin measurement procedures were investigated vs an isotope
      dilution mass spectrometry (IDMS) procedure. Nonfrozen aliquots of freshly
      collected urine from 332 patients with chronic kidney disease, diabetes,
      cardiovascular disease, and hypertension were distributed to manufacturers to
      perform urine albumin measurements according to the respective instructions for
      use for each procedure. Frozen aliquots were used for measurements by the IDMS
      procedure. An error model was used to determine imprecision and bias components.
      RESULTS: Median differences between the largest positive and negative biases vs
      IDMS were 45%, 37%, and 42% in the concentration intervals of 12-30 mg/L, 31-200
      mg/L, and 201-1064 mg/L, respectively. Biases varied with concentration for most
      procedures and exceeded +/- 10% over the concentration interval for 14 of 16
      quantitative procedures. Mean biases ranged from -35% to 34% at 15 mg/L. Dilution
      of samples with high concentrations introduced bias for 4 procedures. The
      combined CV was >10% for 5 procedures. It was not possible to estimate total
      error due to dependence of bias on concentration. CVs for sample-specific
      influences were 0% to 15.2%. CONCLUSIONS: Bias was the dominant source of
      disagreement among routine measurement procedures. Consequently, standardization
      efforts will improve agreement among results. Variation of bias with
      concentration needs to be addressed by manufacturers.

PMID- 24281782
TI  - Impact of tutorial assistance in laparoscopic sigmoidectomy for acute recurrent
      diverticulitis.
AB  - PURPOSE: Adequate training and close supervision by an experienced surgeon are
      crucial to assure the patient safety during laparoscopic training. This study
      evaluated the impact of tutorial assistance on the duration of surgery and
      postoperative complications after laparoscopic sigmoidectomy. METHODS: The data
      from 235 patients undergoing laparoscopic sigmoidectomy were collected. Operating
      surgeons were classified as either residents/registrars (group A, tutorial
      assistance) or consultants operating autonomously (group B). Groups were compared
      concerning the duration of surgery and in-hospital complications using a
      multivariable regression model accounting for the most relevant confounders.
      RESULTS: The median duration of the operation in group A (n = 75) was 221 min,
      and that in group B (n = 160) 189 min (p < 0.001). The risk of developing any in
      hospital complication (Clavien-Dindo classification I-V) was 36.0 % in Group A
      and 32.5 % in group B (95 % CI -16.6, 9.6 %). The risk of developing moderate to
      severe surgical complications (Clavien-Dindo classification II-V) was 16.0 % in
      group A and 12.5 % in group B (95 % CI -13.3, 6.3 %). CONCLUSIONS: We were unable
      to demonstrate a clear impact of tutorial assistance on the risk of postoperative
      complications. Although associated with a longer duration of surgery,
      laparoscopic sigmoidectomy for acute recurrent sigmoid diverticulitis conducted
      by a junior supervised surgeon appears to be a safe surgical modality.

PMID- 24281783
TI  - Clinical presentation and morbidity of contact lens-associated microbial
      keratitis: a retrospective study.
AB  - PURPOSE: To investigate the clinical presentation, isolated organism, treatment,
      and morbidity of contact lens-associated microbial keratitis needing
      hospitalization. METHODS: This retrospective study included all consecutive
      patients with contact lens-associated microbial keratitis hospitalized in the
      Rotterdam Eye Hospital from January 1, 2005, to December 31, 2009. All data
      regarding epidemiological characteristics, clinical presentation, isolated
      organism, and treatment were collected from medical records. RESULTS: There were
      109 cases (108 patients) of contact lens-associated microbial keratitis
      hospitalized during the study period. Mean age was 33.3 +/- 15.4 (SD) years.
      Pseudomonas aeruginosa was the most frequently isolated microorganism (68.8 %),
      with minor resistance to gentamicin (2.7 %) and ofloxacin (1.3 %). At time of
      presentation, best corrected visual acuity (BCVA) was very poor, with the largest
      proportion of patients (65.1 %) seeing worse than 0.05 Snellen. After intensive
      treatment, the visual outcome improved considerably, with the largest proportion
      (67.0 %) achieving a BCVA >= 0.7 Snellen. Low BCVA at admission was significantly
      associated with a worse final BCVA. A total of 22 patients (20.2 %) required
      corneal transplantation (three emergency cases). Larger size of stromal
      infiltrate was significantly associated with the need for corneal
      transplantation. CONCLUSION: Microbial keratitis is a serious complication of
      contact lens wear, with approximately one out of five hospitalized cases
      requiring corneal transplantation. Ofloxacin, or a combination of gentamicin and
      cephazolin, still appear to be excellent first-choice therapies in the
      Netherlands, as little resistance has developed to these antibiotics.

PMID- 24281784
TI  - The incidental findings of age-related macular degeneration during diabetic
      retinopathy screening.
AB  - BACKGROUND: The purpose of this study was to determine the reliability of
      detecting age-related macular degeneration (AMD) during screening for diabetic
      retinopathy (DR). METHODS: This prospective study included 2,003 subjects with
      diabetes mellitus who underwent photographic screening for DR. The reliability of
      detecting AMD lesions was tested by interobserver and intraobserver agreement,
      and the sensitivity and specificity of diagnosing AMD at different grades of
      severity were tested using the consensus grading of a group as the reference
      standard. RESULTS: DR affected 24.7% of the subjects. The age-standardized
      prevalence of early AMD was 17.9%, and late AMD was 0.1%. The interobserver and
      intraobserver agreement for grading AMD was substantial (k = 0.72 and 0.71
      respectively, p < 0.001). It was equally good in those with different severities
      of DR. There was also no difference in sensitivity and specificity of detecting
      AMD in those with different levels of DR (sensitivity 62-68% and specificity 97
      98%). CONCLUSION: Intermediate- and high-risk AMD that warrant treatment with
      zinc and anti-oxidant supplements could be reliably detected during screening for
      diabetic retinopathy.

PMID- 24281785
TI  - Higher optic nerve sheath diameters are associated with lower ocular blood flow
      velocities in glaucoma patients.
AB  - PURPOSE: To investigate the relationship between optic nerve sheath diameter
      (ONSD) and retrobulbar blood flow velocities, as measured by color Doppler
      imaging (CDI) in glaucoma patients. METHODS: We performed a prospective,
      randomized, observer-masked study involving a total of 197 subjects. Once
      enrolled, they were divided by three groups: healthy controls (n = 51), normal
      tension glaucoma patients (NTG, n = 58), and primary, open-angle glaucoma
      patients (POAG, n = 88). All subjects underwent a general ophthalmological
      examination, an ultrasound-based assessment of the ONSD, and a hemodynamic study
      of the retrobulbar vascularization using CDI. Non-parametric tests, chi-square
      contingency tables, and the Deming correlations were used to explore differences
      and correlations between variables in the diagnostic groups. RESULTS: ONSD was
      not different between experimental groups (p = 0.28). ONSD correlated positively
      with the pulsatility index of the ophthalmic artery in healthy individuals (p =
      0.007), but not in glaucoma patients (NTG: p = 0.41; POAG: p = 0.22). In NTG
      patients, higher ONSD values were associated with lower end-diastolic and mean
      flow velocities in the short ciliary arteries (p = 0.005 in both correlations).
      No such correlation was found in healthy nor POAG groups (p range between 0.15 to
      0.96). ONSD was not associated with any CDI-related variable of the central
      retinal artery in any cohort. Venous outflow velocities were not associated with
      ONSD in any of the three groups. CONCLUSIONS: ONSD is negatively correlated with
      retrobulbar blood flow velocities in glaucoma patients, but not in healthy
      controls.

PMID- 24281786
TI  - MMN and novelty P3 in coma and other altered states of consciousness: a review.
AB  - In recent decades, there has been a growing interest in the assessment of
      patients in altered states of consciousness. There is a need for accurate and
      early prediction of awakening and recovery from coma. Neurophysiological
      assessment of coma was once restricted to brainstem auditory and primary cortex
      somatosensory evoked potentials elicited in the 30 ms range, which have both
      shown good predictive value for poor coma outcome only. In this paper, we review
      how passive auditory oddball paradigms including deviant and novel sounds have
      proved their efficiency in assessing brain function at a higher level, without
      requiring the patient's active involvement, thus providing an enhanced tool for
      the prediction of coma outcome. The presence of an MMN in response to deviant
      stimuli highlights preserved automatic sensory memory processes. Recorded during
      coma, MMN has shown high specificity as a predictor of recovery of consciousness.
      The presence of a novelty P3 in response to the subject's own first name
      presented as a novel (rare) stimulus has shown a good correlation with coma
      awakening. There is now a growing interest in the search for markers of
      consciousness, if there are any, in unresponsive patients (chronic vegetative or
      minimally conscious states). We discuss the different ERP patterns observed in
      these patients. The presence of novelty P3, including parietal components and
      possibly followed by a late parietal positivity, raises the possibility that some
      awareness processes are at work in these unresponsive patients.

PMID- 24281787
TI  - [What is ascertained in the therapy of axial spondyloarthritis?].
AB  - The new term axial spondyloarthritis (axSpA) includes classic ankylosing
      spondylitis and non-radiographic (nr-) axSpA. The definition was introduced in
      2009 as part of the Assessment of SpondyloArthritis international Society (ASAS)
      classification criteria for axSpA, where-apart from chronic back pain starting
      before the age of 45 years and the presence of HLA-B27-magnetic resonance imaging
      demonstrated bone marrow edema of the sacroiliac joints (osteomyelitis) or
      structural changes on x-rays may play an important role. These criteria can also
      be used for diagnosis. A major advantage of the new criteria is the
      identification of patients in early disease stages. In addition to physical
      therapy, drug treatment with steroidal anti-inflammatory agents (NSAIDs),
      corticosteroid injections, and biologics [blocker of tumor necrosis factor (TNF)]
      have all been shown to be effective, while conventional disease modifying drugs
      (DMARDs) such as sulfasalazine and methotrexate seem to work mainly for
      peripheral arthritis but not for enthesitis. Biologics are indicated when NSAIDs
      in optimal dosage have failed. Both these drugs have the potential to improve
      pain, stiffness, and function but they may also have an influence on new bone
      formation (syndesmophytes). NSAIDs need to be given continuously and biologics
      for longer periods of time. Patients with elevated C-reactive protein levels
      benefit most when treated consequently. 

PMID- 24281788
TI  - Gastrointestinal bleeding after high intake of omega-3 fatty acids, cortisone and
      antibiotic therapy: a case study.
AB  - Omega-3 fatty acids exert a plethora of physiological actions including
      triglycerides lowering, reduction of inflammatory indices, immunomodulation, anti
      thrombotic effects and possibly promotion of exercise performance. Their use is
      widespread and for commonly ingested doses their side- effects are minimal. We
      report a case of a 60 y amateur athlete who consumed about 20 g omega-3 fatty
      acids daily from supplements and natural sources for a year. After the intake of
      cortisone and antibiotics he presented duodenum ulcer and bleeding although he
      had no previous history of gastrointestinal problems. Although several animal
      data support gastro-protective effects of omega-3 fatty acids in the present case
      they were not able to prevent ulcer generation. The present observation may be
      explained by (i) the high dose of omega-3 fatty acids and their effect on
      bleeding, (ii) the fact that cortisone increases their oxidation and may render
      them proinflammatory, (iii) other antithrombotic microconstituents included in
      the consumed cod-oil and/or the diet of the subject and (iv) the differences in
      the coagulation and fibrinolytic systems of well- trained subjects. Further
      studies are needed to substantiate any possible interaction of cortisone and
      omega-3 fatty acids in wide ranges of intake.

PMID- 24281789
TI  - Effect of treating psoriasis on cardiovascular co-morbidities: focus on TNF
      inhibitors.
AB  - Psoriasis patients are at increased risk for cardiovascular disease. Literature
      on rheumatoid arthritis has shown the association of treatment with tumor
      necrosis factor (TNF) inhibitors and improvement of cardiovascular disease.
      Recent literature has also shown similar findings in psoriasis patients. We
      present a review of the literature on the effect of TNF inhibitors for psoriasis
      treatment on cardiovascular disease, cardiovascular biomarkers, and insulin
      resistance. We conclude that TNF inhibitors may be especially beneficial in
      preventing myocardial infarction, to a degree greater than methotrexate,
      especially in the Caucasian population. The effects of TNF inhibitors in altering
      insulin sensitivity or preventing new onset diabetes have been contradictory.
      Case reports of both hyperglycemia and hypoglycemia developing in patients under
      TNF inhibitor treatment teach us to warn patients about these side effects. More
      robust clinical studies are needed to evaluate the true effect of TNF inhibitors
      in diabetic psoriasis patients. More studies are also needed to assess the effect
      of TNF inhibitors on hypertension, dyslipidemia, and stroke. 

PMID- 24281790
TI  - Safety and tolerability of tumor necrosis factor-alpha inhibitors in psoriasis: a
      narrative review.
AB  - Tumor necrosis factor (TNF)-alpha inhibitors are an alternative to oral systemic
      therapies for psoriasis. Data regarding the safety of TNF-alpha inhibitors from
      randomized clinical trials may not fully reflect the effects on the clinic
      patient population receiving the therapy, but other sources of information are
      available. We performed a literature review to assess the safety and tolerability
      of the treatment of moderate-to-severe plaque psoriasis with TNF-alpha
      inhibitors. A literature search was conducted using PubMed for articles dating
      from January 2000 to October 2013. Randomized controlled, cohort, open-label, and
      observational studies were included, as well as case reports and letters to the
      editor. Articles found on PubMed describing the safety of anti-TNF-alpha therapy
      in psoriasis patients were included, while studies highlighting interleukin (IL)
      12 and IL-23 inhibitors were excluded, as were non-English articles. In total, 58
      articles were included in the review. TNF-alpha inhibitors exhibit both efficacy
      and tolerability in patients with moderate-to-severe plaque psoriasis. Adverse
      effects associated with these medications are not common and can be minimized
      with routine clinical monitoring and patient education. While the risk of severe
      adverse events is low, the lack of very large, long-term, randomized safety
      trials limits the ability to fully define the safety of these agents. TNF-alpha
      inhibitors have a good efficacy/safety ratio for use in patients with moderate-to
      severe psoriasis. Serious adverse effects are not common, and common injection
      site reactions are usually manageable. The benefits of TNF-alpha inhibitors
      outweigh the risks for moderate-to-severe psoriasis; however, there are potential
      adverse effects and the patient populations at highest risk include the elderly
      and those with a history of malignancy. 

PMID- 24281791
TI  - Synthesis of a DNA promoter segment containing all four epigenetic nucleosides: 5
      methyl-, 5-hydroxymethyl-, 5-formyl-, and 5-carboxy-2'-deoxycytidine.
AB  - A 5-formyl-2'-deoxycytidine (fdC) phosphoramidite building block that enables the
      synthesis of fdC-containing DNA with excellent purity and yield has been
      developed. In combination with phosphoramidites for 5-methyl-dC, 5-hydroxymethyl
      dC, and carboxy-dC, it was possible to prepare a segment of the OCT-4 promoter
      that contains all four epigenetic bases. Because of the enormous interest in
      these new epigenetic bases, the ability to insert all four of them into DNA
      should be of great value for the scientific community. 

PMID- 24281793
TI  - Characterization of an allelic series in the MONOPTEROS gene of Arabidopsis.
AB  - Patterning of numerous features of plants depends on transduction of the auxin
      signal. Auxin signaling is mediated by several pathways, the best understood of
      which relies on the function of the MONOPTEROS (MP) gene. Seven mp mutant alleles
      have been described in the widely used Columbia background of Arabidopsis: two
      extensively characterized and five only partially characterized. One of these
      five mp alleles appears to be extinct and thus unavailable for analysis. We show
      that two of the four remaining, partially characterized mp alleles reported to be
      in the Columbia background are in fact not in this background. We extend
      characterization of the remaining two Columbia alleles of mp, and we identify and
      characterize four new alleles of mp in the Columbia background, among which the
      first low-expression allele of mp and the strongest Columbia allele of mp. These
      genetic resources provide the research community with new experimental
      opportunities for insight into the function of MP-dependent auxin signaling in
      plant development.

PMID- 24281792
TI  - Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic
      acinar AR42J cells.
AB  - Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing
      significant morbidity and mortality. Due to lack of a suitable animal model, the
      underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits
      alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to
      fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic
      ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs
      and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which
      express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1.
      Therefore, the present study was undertaken to investigate the role of various
      ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury.
      Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4
      methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)],
      cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide)
      followed by incubation with 800 mg% ethanol at 37 degrees C for 6 h. Ethanol
      metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell
      proliferation status, and formation of FAEEs in AR42J cells were measured. The
      cell viability and cell proliferation rate were significantly reduced in cells
      pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ
      formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol
      and ~1.5-fold in those treated with 4-MP + ethanol vs. respective controls.
      However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in
      combination of ethanol showed no significant changes either for FAEE formation,
      cell death or proliferation rate. Therefore, an impaired ADH class I-III
      catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol
      induced pancreatic injury via formation of nonoxidative metabolites of ethanol.

PMID- 24281794
TI  - From needles to pattern in food quality determination.

PMID- 24281797
TI  - Towards polyoxometalate-cluster-based nano-electronics.
AB  - We explore the concept that the incorporation of polyoxometalates (POMs) into
      complementary metal oxide semiconductor (CMOS) technologies could offer a
      fundamentally better way to design and engineer new types of data storage
      devices, due to the enhanced electronic complementarity with SiO2, high redox
      potentials, and multiple redox states accessible to polyoxometalate clusters. To
      explore this we constructed a custom-built simulation domain bridge. Connecting
      DFT, for the quantum mechanical modelling part, and mesoscopic device modelling,
      confirms the theoretical basis for the proposed advantages of POMs in non
      volatile molecular memories (NVMM) or flash-RAM.

PMID- 24281798
TI  - Binding of CO2 by a Mes2PCH2CH2B(C6F5)2 species: an involvement of the ground
      state species in a low-energy pathway.

PMID- 24281799
TI  - Organocatalytic enantioselective cycloaddition reactions of dienamines with
      quinones.

PMID- 24281800
TI  - meso-meso-linked subporphyrin dimer.

PMID- 24281801
TI  - Disproportionation of achiral nickel(II) centers into two kinds of chiral
      nickel(II) centers caused by an achiral diimine ligand.

PMID- 24281802
TI  - Rhodium-catalyzed spirocyclic sultam synthesis by [3+2] annulation with cyclic N
      sulfonyl ketimines and alkynes.

PMID- 24281803
TI  - syn- and enantioselective Henry reactions of aliphatic aldehydes and application
      to the synthesis of safingol.

PMID- 24281804
TI  - Punching a carbon atom of C60 into its own cavity to form an endohedral complex
      CO@C59O6 under mild conditions.

PMID- 24281805
TI  - Water-compatible hydrogen-bond activation: a scalable and organocatalytic model
      for the stereoselective multicomponent aza-Henry reaction.

PMID- 24281806
TI  - 4-Trifluoromethyl-substituted coumarins with large Stokes shifts: synthesis,
      bioconjugates, and their use in super-resolution fluorescence microscopy.
AB  - Bright and photostable fluorescent dyes with large Stokes shifts are widely used
      as sensors, molecular probes, and light-emitting markers in chemistry, life
      sciences, and optical microscopy. In this study, new 7-dialkylamino-4
      trifluoromethylcoumarins have been designed for use in bioconjugation reactions
      and optical microscopy. Their synthesis was based on the Stille reaction of 3
      chloro-4-trifluoromethylcoumarins and available (hetero)aryl- or
      (hetero)arylethenyltin derivatives. Alternatively, the acylation of 2
      trifluoroacetyl-5-dialkylaminophenols with available (hetero)aryl- or
      (hetero)arylethenylacetic acids followed by intramolecular condensation afforded
      coumarins with 3-(hetero)aryl or 3-[2-(hetero)aryl]ethenyl groups. Hydrophilic
      properties were provided by the introduction of a sulfonic acid residue or by
      phosphorylation of a primary hydroxy group attached at C-4 of the 2,2,4-trimethyl
      1,2-dihydroquinoline fragment fused to the coumarin fluorophore. For use in
      immunolabeling procedures, the dyes were decorated with an (activated) carboxy
      group. The positions of the absorption and emission maxima vary in the ranges 413
      480 and 527-668 nm, respectively. The phosphorylated dye, 9,CH=CH-2-py,H, with
      the 1-(3-carboxypropyl)-4-hydroxymethyl-2,2-dimethyl-1,2-dihydroquinoline
      fragment fused to the coumarin fluorophore bearing the 3-[2-(2-pyridyl)ethenyl]
      residue (absorption and emission maxima at 472 and 623 nm, respectively) was used
      in super-resolution light microscopy with stimulated emission depletion and
      provided an optical resolution better than 70 nm with a low background signal. As
      a result of their large Stokes shifts, good fluorescence quantum yields, and
      adequate photostabilities, phosphorylated coumarins enable two-color imaging
      (using several excitation sources and a single depletion laser) to be combined
      with subdiffractional optical resolution.

PMID- 24281807
TI  - Supramolecular assembly of bis(benzimidazole)pyridine: an extended anisotropic
      ligand for highly birefringent materials.
AB  - Four new bis(benzimidazole)pyridine (BBP)-containing compounds
      Zn(BBP)Cl[Au(CN)2], Mn(BBP)[Au(CN)2]2.H2O, Mn(BBP)Br2(MeOH) and
      Mn(BBP)Cl2(MeOH).MeOH have been synthesized and structurally characterized and
      their birefringence values (Deltan) determined. The structure of
      Zn(BBP)Cl[Au(CN)2] contains a hydrogen-bonded dimer of Zn(BBP)Cl[Au(CN)2] units
      which propagate into a 1D chain through Au-Au interactions, although the crystals
      are of poor optical quality. The supramolecular structure of Mn(BBP)[Au(CN)2]2.H2
      O forms a 1D coordination polymer through chains of Mn(BBP)[Au(CN)2]2 units, each
      containing one bridging Au(CN)2 and one forming a 2D sheet through Au-Au
      interactions. The supramolecular structures of Mn(BBP)Br2(MeOH) and
      Mn(BBP)Cl2(MeOH).MeOH are very similar, consisting of a complex hydrogen-bonded
      network between NH imidazole, methanol and halide groups to align BBP building
      blocks. In the plane of the primary crystal growth direction, the birefringence
      values of the three Mn-containing materials were Deltan=0.08(1), 0.538(3) and
      0.69(3), respectively. The latter two birefringence values are larger than in the
      related 2,2';6'2''-terpyridine systems, placing them among the most birefringent
      solids reported. These compounds illustrate the utility of extending the pi
      system of the building block and incorporating hydrogen-bonding sites as design
      elements for highly birefringent materials and also illustrates the effect on the
      measurable birefringence of the crystal quality, growth direction and structural
      alignment of the anisotropic BBP building blocks.

PMID- 24281808
TI  - Identification of intermediates in zeolite-catalyzed reactions by in situ UV/Vis
      microspectroscopy and a complementary set of molecular simulations.
AB  - The optical absorption properties of (poly)aromatic hydrocarbons occluded in a
      nanoporous environment were investigated by theoretical and experimental methods.
      The carbonaceous species are an essential part of a working catalyst for the
      methanol-to-olefins (MTO) process. In situ UV/Vis microscopy measurements on
      methanol conversion over the acidic solid catalysts H-SAPO-34 and H-SSZ-13
      revealed the growth of various broad absorption bands around 400, 480, and 580
      nm. The cationic nature of the involved species was determined by interaction of
      ammonia with the methanol-treated samples. To determine which organic species
      contribute to the various bands, a systematic series of aromatics was analyzed by
      means of time-dependent density functional theory (TDDFT) calculations. Static
      gas-phase simulations revealed the influence of structurally different
      hydrocarbons on the absorption spectra, whereas the influence of the zeolitic
      framework was examined by using supramolecular models within a quantum
      mechanics/molecular mechanics framework. To fully understand the origin of the
      main absorption peaks, a molecular dynamics (MD) study on the organic species
      trapped in the inorganic host was essential. During such simulation the
      flexibility is fully taken into account and the effect on the UV/Vis spectra is
      determined by performing TDDFT calculations on various snapshots of the MD run.
      This procedure allows an energy absorption scale to be provided and the various
      absorption bands determined from in situ UV/Vis spectra to be assigned to
      structurally different species.

PMID- 24281809
TI  - Solvent-induced helical assembly and reversible chiroptical switching of chiral
      cyclic-dipeptide-functionalized naphthalenediimides.
AB  - Understanding the roles of various parameters in orchestrating the preferential
      chiral molecular organization in supramolecular self-assembly processes is of
      great significance in designing novel molecular functional systems. Cyclic
      dipeptide (CDP) chiral auxiliary-functionalized naphthalenediimides (NCDPs 1-6)
      have been prepared and their chiral self-assembly properties have been
      investigated. Detailed photophysical and circular dichroism (CD) studies have
      unveiled the crucial role of the solvent in the chiral aggregation of these
      NCDPs. NCDPs 1-3 form supramolecular helical assemblies and exhibit remarkable
      chiroptical switching behaviour (M- to P-type) depending on the solvent
      composition of HFIP and DMSO. The strong influence of solvent composition on the
      supramolecular chirality of NCDPs has been further corroborated by concentration
      and solid-state thin-film CD studies. The chiroptical switching between
      supramolecular aggregates of opposite helicity (M and P) has been found to be
      reversible, and can be achieved through cycles of solvent removal and
      redissolution in solvent mixtures of specific composition. The control molecular
      systems (NCDPs 4-6), with an achiral or D-isomer second amino acid in the CDP
      auxiliary, did not show chiral aggregation properties. The substantial roles of
      hydrogen bonding and pi-pi interactions in the assembly of the NCDPs have been
      validated through nuclear magnetic resonance (NMR), photophysical, and
      computational studies. Quantum chemical calculations at the ab initio,
      semiempirical, and density functional theory levels have been performed on model
      systems to understand the stabilities of the right (P-) and left (M-) handed
      helical supramolecular assemblies and the nature of the intermolecular
      interactions. This study emphasizes the role of CDP chiral auxiliaries on the
      solvent-induced helical assembly and reversible chiroptical switching of
      naphthalenediimides. 

PMID- 24281810
TI  - A self-assembled nanohybrid composed of fluorophore-phenylamine nanorods and Ag
      nanocrystals: energy transfer, wavelength shift of fluorescence and TPEF
      applications for live-cell imaging.
AB  - A fluorophore-phenylamine derivative (L) has been coupled with silver
      nanocrystals (NCs) to construct an L-Ag nanohybrid. Owing to synergic effects of
      the L and Ag components, the exciton-plasmon interactions between L and Ag
      increase the strength of the donor-acceptor interaction within the nanohybrid, a
      fact that results in an energy-transfer process and further brings about a
      dramatic redshift of single-photon absorption and fluorescence, and a decreased
      fluorescence FL lifetime. The coupling effect also leads to enhancement of a
      series of nonlinear optical properties, including two-photon-excited fluorescence
      (TPEF), two-photon-absorption (TPA) cross section (delta), two-photon-absorption
      coefficient (beta), nonlinear refractive index (gamma), and third order nonlinear
      optical susceptibility (chi((3))). The enhanced two-photon fluorescence of the
      nanohybrid is proven to be potentially useful for two-photon microscopy of live
      cells, such as HepG2. Moreover, cytotoxicity tests show that the low-micromolar
      concentrations of the nanohybrid do not cause significant reduction in cell
      viability over a period of at least 24 h and should be safe for further
      biological studies.

PMID- 24281811
TI  - Self-assembled fluorescent organic nanoparticles for live-cell imaging.
AB  - Fluorescent, cell-permeable, organic nanoparticles based on self-assembled pi
      conjugated oligomers with high absorption cross-sections and high quantum yields
      have been developed. The nanoparticles are generated with a tuneable density of
      amino groups for charge-mediated cellular uptake by a straightforward self
      assembly protocol, which allows for control over size and toxicity. The results
      show that a single amino group per ten oligomers is sufficient to achieve
      cellular uptake. The non-toxic nanoparticles are suitable for both one- and two
      photon cellular imaging and flow cytometry, and undergo very efficient cellular
      uptake. 

PMID- 24281812
TI  - Tetrathiafulvalene-based mixed-valence acceptor-donor-acceptor triads: a joint
      theoretical and experimental approach.
AB  - This work presents a joint theoretical and experimental characterisation of the
      structural and electronic properties of two tetrathiafulvalene (TTF)-based
      acceptor-donor-acceptor triads (BQ-TTF-BQ and BTCNQ-TTF-BTCNQ; BQ is
      naphthoquinone and BTCNQ is benzotetracyano-p-quinodimethane) in their neutral
      and reduced states. The study is performed with the use of electrochemical,
      electron paramagnetic resonance (EPR), and UV/Vis/NIR spectroelectrochemical
      techniques guided by quantum-chemical calculations. Emphasis is placed on the
      mixed-valence properties of both triads in their radical anion states. The
      electrochemical and EPR results reveal that both BQ-TTF-BQ and BTCNQ-TTF-BTCNQ
      triads in their radical anion states behave as class-II mixed-valence compounds
      with significant electronic communication between the acceptor moieties. Density
      functional theory calculations (BLYP35/cc-pVTZ), taking into account the solvent
      effects, predict charge-localised species (BQ(.-)-TTF-BQ and BTCNQ(.-)-TTF-BTCNQ)
      as the most stable structures for the radical anion states of both triads. A
      stronger localisation is found both experimentally and theoretically for the
      BTCNQ-TTF-BTCNQ anion, in accordance with the more electron-withdrawing character
      of the BTCNQ acceptor. CASSCF/CASPT2 calculations suggest that the low-energy,
      broad absorption bands observed experimentally for the BQ-TTF-BQ and BTCNQ-TTF
      BTCNQ radical anions are associated with the intervalence charge transfer (IV-CT)
      electronic transition and two nearby donor-to-acceptor CT excitations. The study
      highlights the molecular efficiency of the electron-donor TTF unit as a molecular
      wire connecting two acceptor redox centres.

PMID- 24281813
TI  - Catalytic reduction of graphene oxide nanosheets by glutathione peroxidase
      mimetics reveals a new structural motif in graphene oxide.
AB  - A catalytic reduction of graphene oxide (GO) by glutathione peroxidase (GPx)
      mimics is reported. This study reveals that GO contains peroxide functionalities,
      in addition to the epoxy, hydroxyl and carboxylic acid groups that have been
      identified earlier. It also is shown that GO acts as a peroxide substrate in the
      GPx-like catalytic activity of organoselenium/tellurium compounds. The reaction
      of tellurol, generated from the corresponding ditelluride, reduces GO through the
      glutathione (GSH)-mediated cleavage of the peroxide linkage. The mechanism of GO
      reduction by the tellurol in the presence of GSH involves the formation of a
      tellurenic acid and tellurenyl sulfide intermediates. Interestingly, the GPx
      mimics also catalyze the decarboxylation of the carboxylic acid functionality in
      GO at ambient conditions. Whereas the selenium/tellurium-mediated catalytic
      reduction/decarboxylation of GO may find applications in bioremediation
      processes, this study suggests that the modification of GO by biologically
      relevant compounds such as redox proteins must be taken into account when using
      GO for biomedical applications because such modifications can alter the
      fundamental properties of GO. 

PMID- 24281814
TI  - Stable anilinyl radicals coordinated to nickel: X-ray crystal structure and
      characterization.
AB  - Two anilinosalen and a mixed phenol-anilinosalen ligands involving sterically
      hindered anilines moieties were synthesized. Their nickel(II) complexes 1, 2, and
      3 were prepared and characterized. They could be readily one-electron oxidized
      (E(1/2)=-0.30, -0.26 and 0.10 V vs. Fc(+)/Fc, respectively) into anilinyl
      radicals species [1](+), [2](+), and [3](+), respectively. The radical complexes
      are extremely stable and were isolated as single crystals. X-ray crystallographic
      structures reveal that the changes in bond length resulting from oxidation do not
      exceed 0.02 A within the ligand framework in the symmetrical [1](+) and [2](+).
      No quinoid bond pattern was present. In contrast, larger structural
      rearrangements were evidenced for the unsymmetrical [3](+), with shortening of
      one C(ortho)-C(meta) bond. Radical species [1](+) and [2](+) exhibit a strong
      absorption band at around 6000 cm(-1) (class III mixed valence compounds). This
      band is significantly less intense than [3](+), consistent with a rather
      localized anilinyl radical character, and thus a classification of this species
      as class II mixed-valence compound. Magnetic and electronic properties, as well
      as structural parameters, have been computed by DFT methods.

PMID- 24281815
TI  - Asymmetric alpha-hydroxylation of tetralone-derived beta-ketoesters by using a
      guanidine-urea bifunctional organocatalyst in the presence of cumene
      hydroperoxide.
AB  - Highly enantioselective catalytic oxidation of 1-tetralone-derived beta-keto
      esters was achieved by using a guanidine-urea bifunctional organocatalyst in the
      presence of cumene hydroperoxide (CHP), a safe, commercially available oxidant.
      The alpha-hydroxylation products were obtained in 99% yield with up to 95%
      enantiomeric excess (ee). The present oxidation was successfully applied to
      synthesize a key intermediate of the anti-cancer agent daunorubicin (2).

PMID- 24281816
TI  - BippyPhos: a single ligand with unprecedented scope in the Buchwald-Hartwig
      amination of (hetero)aryl chlorides.
AB  - Over the past two decades, considerable attention has been given to the
      development of new ligands for the palladium-catalyzed arylation of amines and
      related NH-containing substrates (i.e., Buchwald-Hartwig amination). The
      generation of structurally diverse ligands, by research groups in both academia
      and industry, has facilitated the accommodation of sterically and electronically
      divergent substrates including ammonia, hydrazine, amines, amides, and NH
      heterocycles. Despite these achievements, problems with catalyst generality
      persist and access to multiple ligands is necessary to accommodate all of these
      NH-containing substrates. In our quest to address this significant limitation we
      identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of
      catalyzing the amination of a variety of functionalized (hetero)aryl chlorides,
      as well as bromides and tosylates, at moderate to low catalyst loadings. The
      successful transformations described herein include primary and secondary amines,
      NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest
      scope in the NH-containing coupling partner reported for a single Pd/ligand
      catalyst system. We also established BippyPhos/[Pd(cinnamyl)Cl]2 as exhibiting
      the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of
      (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of
      BippyPhos/[Pd(cinnamyl)Cl]2 to catalyze both the selective monoarylation of
      ammonia and the N-arylation of indoles was exploited in the development of a new
      one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho
      alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N
      arylation/hydroamination reactions. Although the scope in the NH-containing
      coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked
      selectivity profile that was exploited in the chemoselective monoarylation of
      substrates featuring two chemically distinct NH-containing moieties.

PMID- 24281817
TI  - Comment on the article "Gutmann donor and acceptor numbers for ionic liquids" by
      M. Schmeisser, P. Illner, R. Puchta, A. Zahl, and R. van Eldik (Chem. Eur. J.
      2012, 18, 10969-10982).

PMID- 24281818
TI  - Liquid crystal organization of self-assembling cyclic peptides.
AB  - Self-assembling cyclic peptides decorated with mesogens form porous columnar
      mesophases in which, depending on the number of hydrocarbon chains, double or
      single channels are formed along each column. 

PMID- 24281819
TI  - Perioperative coagulopathy monitoring.
AB  - Coagulopathy is common in orthopedic surgery patients either due to acquired
      factors, such as surgery, trauma, medications, or hemorrhage. Perioperative
      monitoring of blood coagulation is critical to diagnose the causes of hemorrhage,
      guide hemostatic therapies, predict the risk of bleeding during surgical
      procedures, and reduce risk of postoperative cardiac and thromboembolic events.
      In contrast to previous interventions that measure specific portions of the
      clotting cascade (such as intrinsic or extrinsic pathways or platelet
      aggregation), "Point-of-care" coagulation monitoring devices assess the
      viscoelastic properties of whole blood. These techniques have the potential to
      measure the entire clotting process, starting with fibrin formation, clot
      retraction, and fibrinolysis. Furthermore, the coagulation status of patients is
      assessed in whole blood, allowing the plasmatic coagulation system to interact
      with platelets and red cells, and thereby providing useful additional information
      on platelet function. Improved monitoring of coagulopathy is particularly
      important as new anticoagulant drugs emerge that affect the clotting cascade in
      novel ways, including the inhibition of intrinsic and extrinsic pathways and
      platelet function. It is important for orthopedic surgeons to understand the
      pharmacology and reversal of these drugs in the perioperative setting. The
      purpose of this review is to review the current techniques to monitoring
      perioperative coagulopathy and to identify the manner in which novel
      anticoagulant medications affect the clotting cascade with particular interest in
      trauma and spine surgery. 

PMID- 24281820
TI  - Efficient synthesis of manganese(II) carboxylates: from a trinuclear cluster
      [Mn3(PhCO2)6(THF)4] to a unique [Mn(PhCO2)2]n chiral 3D network.
AB  - An efficient synthetic procedure for obtaining manganese carboxylates including a
      trinuclear cluster [Mn3(PhCO2)6(THF)4]2 and a unique [Mn(PhCO2)2]n chiral 3D
      network is reported. The procedure involves a simple redox process, in which
      acidic protons are reduced to gaseous hydrogen by oxidizing metallic manganese
      under solvothermal conditions. 

PMID- 24281822
TI  - Author's comment on the retraction of "Neuroradiological advances detect abnormal
      neuroanatomy underlying neuropsychological impairments: the power of PET
      imaging".

PMID- 24281821
TI  - FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell
      lymphoma: systematic review and meta-analysis.
AB  - PURPOSE: To systematically review and meta-analyse published data on the
      diagnostic performance of (18)F-FDG PET/CT in detecting bone marrow involvement
      in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS:
      PubMed/MEDLINE and Embase were systematically searched for relevant studies. The
      methodological quality of each study was assessed. Sensitivities and
      specificities of FDG PET/CT in individual studies were calculated and meta
      analysed with a random effects model. A summary receiver operating characteristic
      curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted
      summary proportions of discrepancies between the FDG PET/CT and (blind) bone
      marrow biopsy (BMB) results among all patients were calculated. RESULTS: Seven
      studies, with a total of 654 patients with newly diagnosed DLBCL, were included.
      Overall, the quality of the included studies was moderate. The sensitivity and
      specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8%
      to 95.8% and from 99.0% to 100%, with pooled estimates of 88.7% (95% confidence
      interval, CI, 82.5-93.3%) and 99.8% (95% CI 98.8-100%), respectively. The area
      under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT
      negative patients with positive BMB findings among all patients was 3.1% (95% CI
      1.8-5.0%) and the weighted summary proportion of FDG PET/CT-positive patients
      with negative BMB findings among all patients was 12.5% (95% CI 8.4-17.3%).
      CONCLUSION: FDG PET/CT is accurate and complementary to BMB for detecting bone
      marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT
      scan cannot rule out the presence of bone marrow involvement, but positive FDG
      PET/CT findings obviate the need for BMB for the detection of bone marrow
      involvement in these patients.

PMID- 24281823
TI  - The role of collegial alliance in family-based treatment of adolescent anorexia
      nervosa: a pilot study.
AB  - OBJECTIVE: In keeping with broader efforts to identify mediators and moderators
      of treatment outcome in anorexia nervosa, this pilot study investigated the
      association between collegial alliance, which refers to the perceived alliance
      between case-involved professionals, and treatment outcomes in adolescent
      patients undergoing family-based treatment (FBT) for anorexia nervosa. METHOD:
      The self-reported collegial alliance scores of five FBT practitioners were
      collected, alongside weight- and cognitive-related outcomes for 29 consecutive
      cases of adolescent anorexia nervosa under their care. RESULTS: Collegial
      alliance discriminated between patients who dropped out of treatment and patients
      who completed treatment, t(27) = 3.68, p = .001, eta(2)  = .33. Furthermore,
      there was a strong negative correlation between collegial alliance scores early
      on in treatment and disordered eating symptoms later in treatment, r(23) = -.67,
      p < .001. Moderate but non-significant associations were observed between early
      collegial alliance and patient's percentage of expected body weight later in
      treatment, r(23) = .32, p = .13. DISCUSSION: These findings have important
      implications for the augmentation of FBT, suggesting that unity amongst
      clinicians promotes positive treatment outcomes, particularly with regard to
      disordered eating symptomatology.

PMID- 24281824
TI  - Structural and binding properties of the PASTA domain of PonA2, a key penicillin
      binding protein from Mycobacterium tuberculosis.
AB  - PonA2 is one of the two class A penicillin binding proteins of Mycobacterium
      tuberculosis, the etiologic agent of tuberculosis. It plays a complex role in
      mycobacterial physiology and is spotted as a promising target for inhibitors.
      PonA2 is involved in adaptation of M. tuberculosis to dormancy, an ability which
      has been attributed to the presence in its sequence of a C-terminal PASTA domain.
      Since PASTA modules are typically considered as beta-lactam antibiotic binding
      domains, we determined the solution structure of the PASTA domain from PonA2 and
      analyzed its binding properties versus a plethora of potential binders, including
      the beta-lactam antibiotics, two typical muropeptide mimics, and polymeric
      peptidoglycan. We show that, despite a high structural similarity with other
      PASTA domains, the PASTA domain of PonA2 displays different binding properties,
      as it is not able to bind muropeptides, or beta-lactams, or polymeric
      peptidoglycan. These results indicate that the role of PASTA domains cannot be
      generalized, as their specific binding properties strongly depend on surface
      residues, which are widely variable.

PMID- 24281825
TI  - Short-term high-intensity interval and continuous moderate-intensity training
      improve maximal aerobic power and diastolic filling during exercise.
AB  - PURPOSE: This study examined the effects of short-term high-intensity interval
      training (HIT) and continuous moderate-intensity training (CMT) on cardiac
      function in young, healthy men. METHODS: Sixteen previously untrained men (mean
      age of 25.1 +/- 4.1 years) were randomly assigned to HIT and CMT (n = 8 each) and
      assessed before and after six sessions over a 12-day training period. HIT
      consisted of 8-12 intervals of cycling for 60 s at 95-100% of pre-training
      maximal aerobic power (VO(2max)), interspersed by 75 s of cycling at 10%
      VO(2max). CMT involved 90-120 min of cycling at 65% pre-training VO(2max). Left
      ventricular (LV) function was determined at rest and during submaximal exercise
      (heart rate ~105 bpm) using two-dimensional and Doppler echocardiography.
      RESULTS: Training resulted in increased calculated plasma volume (PV) in both
      groups, accompanied by improved VO(2max) in HIT (HIT: from 39.5 +/- 7.1 to 43.9
      +/- 5.5 mL kg(-1) min(-1); CMT: from 39.9 +/- 5.9 to 41.7 +/- 5.3 mL kg(-1) min(
      1); P < 0.001). Resting LV function was not altered. However, increased exercise
      stroke volume (P = 0.02) and cardiac output (P = 0.02) were observed, secondary
      to increases in end-diastolic volume (P < 0.001). Numerous Doppler and speckle
      tracking indices of diastolic function were similarly enhanced during exercise in
      both training groups and were related to changes in PV. CONCLUSION: Short-term
      HIT and CMT elicit rapid improvements in VO2max and LV filling without global
      changes in cardiac performance at rest.

PMID- 24281827
TI  - Anxious forms of depression.
AB  - Previous research has described distinctive features for anxious and nonanxious
      forms of major depression. The concept of "mixed anxiety depression disorder"
      (MADD) refers to a milder degree of the anxious form of depression, since the
      depressive symptoms fall short of the number required for a diagnosis of major
      depression. It is argued that this can be thought of as a subclinical form of
      anxious depression, rather than a separate disorder in its own right. In view of
      its substantial prevalence in general medical settings, its associated disability
      and its public health importance, it deserves to be recognized, and seen as being
      continuous with the more severe forms of anxious depression. It will therefore be
      included in the Field Trials of the version of the ICD-11 (where ICD is the
      International Classification of Disease) intended for primary care. It is argued
      that current anxiety, depression (without anxiety), and anxious depression would
      cover most of the psychologically distressed patients seen in general medical
      settings, using a pseudodimensional system.

PMID- 24281826
TI  - Effect of neuromuscular electrical stimulation intensity over the tibial nerve
      trunk on triceps surae muscle fatigue.
AB  - PURPOSE: This study was designed to investigate whether the intensity modulation
      of a neuromuscular electrical stimulation (NMES) protocol delivered over the
      nerve trunk of the plantar flexors would lead to differential peripheral and
      central contributions of muscle fatigue. METHODS: Three fatiguing isometric
      protocols of the plantar flexors matched for the same amount of isometric torque
      time integral (TTI) were randomly performed including a volitional protocol at 20
      % of the maximal voluntary contraction (MVC) and two NMES protocols (one at
      constant intensity, CST; the other at intensity level progressively adjusted to
      maintain 20 % of MVC, PROG). RESULTS: No time x protocol interaction was found
      for any of the variables. The MVC decreased similarly (~12 %, p < 0.001) after
      all protocols, so did the potentiated twitch responses (p = 0.001). Although
      voluntary activation of the plantar flexors did not change, maximal H-reflex to M
      wave ratio of the soleus (SOL) and the gastrocnemius medialis (GM) muscles showed
      an overall increase (SOL: p = 0.037, GM: p = 0.041), while it remained stable for
      the gastrocnemius lateralis muscle (p = 0.221). A main time effect was observed
      only for the SOL maximal V-wave to the superimposed M-wave ratio (p = 0.024) and
      to the superimposed H-reflex (p = 0.008). While similar central and peripheral
      adaptations were observed after the three fatiguing protocols, the individual
      contribution of the three different triceps surae muscles was different.
      CONCLUSION: Whether the current intensity was increased or not, the adaptations
      after a NMES protocol yield to similar muscle fatigue adaptations as voluntary
      contractions likely through similar pathways matching a similar TTI.

PMID- 24281829
TI  - Ethical issues in decision making by hospital health committee members in Turkey.
AB  - Hospital health committees (HHC) in Turkey review medical reports from clinical
      practitioners and decide whether or not they are justified. As a rule, each HHC
      member is expected to observe and examine each patient and then evaluate the
      report. If the report from the patient's doctor is approved, then the Social
      Security Administration, a state organisation, will meet all of the patient's
      expenses covering treatment, medication and operations. Justification of health
      expenditure is crucial for the state because health resources have to be
      carefully allocated. Conflicts of obligation also generate ethical issues which
      have to be resolved as well. However, HHCs are not designed to make ethical
      decisions. An overall concept of organisational ethics needs to be developed. 

PMID- 24281828
TI  - Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with
      stem-like properties.
AB  - The cyclooxygenase pathway is strongly implicated in breast cancer progression
      but the role of this pathway in the biology of breast cancer stem/progenitor
      cells has not been defined. Recent attention has focused on targeting the
      cyclooxygenase 2 (COX-2) pathway downstream of the COX-2 enzyme by blocking the
      activities of individual prostaglandin E (EP) receptors. Prostaglandin E receptor
      4 (EP4) is widely expressed in primary invasive ductal carcinomas of the breast
      and antagonizing this receptor with small molecule inhibitors or shRNA directed
      to EP4 inhibits metastatic potential in both syngeneic and xenograft models.
      Breast cancer stem/progenitor cells are defined as a subpopulation of cells that
      drive tumor growth, metastasis, treatment resistance, and relapse. Mammosphere
      forming breast cancer cells of human (MDA-MB-231, SKBR3) or murine (66.1, 410.4)
      origin of basal-type, Her-2 phenotype and/or with heightened metastatic capacity
      upregulate expression of both EP4 and COX-2 and are more tumorigenic compared to
      the bulk population. In contrast, luminal-type or non-metastatic counterparts
      (MCF7, 410, 67) do not increase COX-2 and EP4 expression in mammosphere culture.
      Treatment of mammosphere-forming cells with EP4 inhibitors (RQ-15986, AH23848,
      Frondoside A) or EP4 gene silencing, but not with a COX inhibitor (Indomethacin)
      reduces both mammosphere-forming capacity and the expression of phenotypic
      markers (CD44(hi)/CD24(low), aldehyde dehydrogenase) of breast cancer stem cells.
      Finally, an orally delivered EP4 antagonist (RQ-08) reduces the tumor-initiating
      capacity and markedly inhibits both the size of tumors arising from
      transplantation of mammosphere-forming cells and phenotypic markers of stem cells
      in vivo. These studies support the continued investigation of EP4 as a potential
      therapeutic target and provide new insight regarding the role of EP4 in
      supporting a breast cancer stem cell/tumor-initiating phenotype. 

PMID- 24281830
TI  - Work Rehabilitation Questionnaire (WORQ): development and preliminary
      psychometric evidence of an ICF-based questionnaire for vocational
      rehabilitation.
AB  - PURPOSE: The International Classification of Functioning, Disability and Health
      (ICF) has proven to be a valuable framework for vocational rehabilitation (VR).
      No reliable and valid ICF-based instruments to capture work functioning is known,
      hence, the aims of this study were: (1) to outline the process for developing an
      ICF-based questionnaire, the Work Rehabilitation Questionnaire (WORQ) to assess
      functioning in VR and (2) to report preliminary psychometric evidence. METHODS:
      ICF categories were selected from the ICF Core Sets for VR using explorative
      Rasch-analysis and VR literature review. Questions were worded to assess
      identified ICF categories. WORQ was translated from English to German.
      Psychometrics for the German version of WORQ was examined in one VR centre in
      Switzerland. RESULTS: 44 ICF categories were selected which resulted in 36
      questions related to functioning. The psychometric evaluation of WORQ showed high
      test-retest reliability (Spearman correlation 0.79) (n = 53) and good internal
      consistency (Cronbachs Alpha 0.88) (n = 74) WORQ showed moderate correlation with
      Beck Depression Inventory II (Spearman correlation 0.511) and low correlation
      (Spearman correlation -0.353) with SF-36. CONCLUSIONS: WORQ appears to be a
      reliable, ICF-based questionnaire to evaluate functioning in VR, easy to
      administer by health or vocational professionals. The additional information
      gained when using WORQ would contribute to improving interdisciplinary
      understanding of the patient's situation and therefore support the integrative
      planning of the return-to-work process or engagement in gainful employment.
      However, further studies are needed to further examine its use in clinical
      practice and research, when validated in other patient populations and settings.

PMID- 24281831
TI  - Increased expression of S100A6 promotes cell proliferation and migration in human
      hepatocellular carcinoma.
AB  - High levels of S100A6 have been associated with poor outcome in some types of
      human cancers, but the role of S100A6 in the molecular pathogenesis of these
      cancers is largely unknown. This study was performed to explore the expression
      and functional roles of S100A6 in hepatocellular carcinoma (HCC). The expression
      level of S100A6 in HCC tumor and corresponding peritumoral tissues were
      determined by immunohistochemistry analysis. The potential functions of S100A6 in
      tumorigenesis and metastasis were analyzed by cell proliferation, migration, and
      invasion assays in human liver cancer cells. Moreover, through expression and
      purification of S100A6 recombinant protein tagged with cell-penetrating peptide,
      we analyzed its complex extracellular/intracellular effects in a S100A6-silenced
      cellular model. As a result, the expression of S100A6 was up-regulated in human
      HCC compared with adjacent peritumoral tissues. S100A6 silencing inhibited the
      growth and motility of HCC cells, while intracellular re-expression of S100A6
      could rescue the proliferation and migration defects. Intracellular over
      expression of S100A6 resulted in down-regulation of E-cadherin expression and
      promoted nuclear accumulation of beta-catenin. Moreover, we found that the
      enhanced cell proliferation and motility after S100A6 stimulation were dependent
      on the activation of PI3K/AKT pathway. These results suggest that S100A6 may be
      involved in promotion and progression of human liver cancer. KEY MESSAGES: S100A6
      is overexpressed in human hepatocellular carcinoma clinical specimens. S100A6
      promotes proliferation and migration of human hepatoma cells. Overexpression of
      S100A6 results in alteration of E-cadherin and beta-catenin. The multi-effects of
      S100A6 may be mediated in part by PI3K/AKT pathway activation.

PMID- 24281832
TI  - The relationship between body mass index and physical activity levels in relation
      to bone mineral density in premenopausal and postmenopausal women.
AB  - We prospectively analyzed 283 women to evaluate the effects of body mass index
      (BMI) and physical activity levels on bone mineral density (BMD) progression in
      pre- and postmenopausal women over 2 years. In postmenopausal women, lower BMI
      was linked with worsening BMD, and moderate activity levels were associated with
      a lower likelihood of worsening BMD at 2 years. PURPOSE: The aim of our study is
      to evaluate the effects of BMI and physical activity levels on BMD progression in
      pre- and postmenopausal Asian women over 2 years. METHODS: We prospectively
      analyzed 283 women from 2006 to 2009. They were divided into two groups (159 pre-
      and 124 postmenopausal) and analyzed separately to avoid confounding by age and
      menopausal hormonal status. The mean follow-up period was 771 days. Demographic
      data was obtained, including medical history, calcium supplementation, BMI, and
      physical activity levels (IPAQ scale). Bilateral femoral neck BMD was determined
      at the time of recruitment, 1 year, and after 2 years. Generalized linear
      modeling was used to evaluate the effects of BMI and physical activity levels on
      BMD progression over a 2-year period. RESULTS: Amongst premenopausal women, lower
      initial femoral neck BMD scores were linked to worsening BMD (p = 0.048). In
      postmenopausal women, lower BMI was linked with worsening BMD (p = 0.012).
      Postmenopausal patients with moderate activity levels had a lower likelihood of
      worsening BMD at 2 years (p = 0.038). High physical activity levels were linked
      to a lower risk of BMD worsening (p = 0.066). CONCLUSIONS: Higher BMI scores are
      protective for osteoporosis in postmenopausal women. Moderate levels of physical
      activity are beneficial for bone health in postmenopausal women, while low
      physical activity levels are not helpful. We recommend that, in the secondary
      prevention of osteoporosis, postmenopausal women should be encouraged to
      participate regularly in moderate physical activities. A practical approach would
      be walking 30 min a day for at least 5 days per week.

PMID- 24281833
TI  - Higher sensitivity of pad2-1 and vtc2-1 mutants to cadmium is related to lower
      subcellular glutathione rather than ascorbate contents.
AB  - Cadmium (Cd) interferes with ascorbate and glutathione metabolism as it induces
      the production of reactive oxygen species (ROS), binds to glutathione due to its
      high affinity to thiol groups, and induces the production of phytochelatins (PCs)
      which use glutathione as a precursor. In this study, changes in the compartment
      specific distribution of ascorbate and glutathione were monitored over a time
      period of 14 days in Cd-treated (50 and 100 MUM) Arabidopsis Col-0 plants, and
      two mutant lines deficient in glutathione (pad2-1) and ascorbate (vtc2-1). Both
      mutants showed higher sensitivity to Cd than Col-0 plants. Strongly reduced
      compartment specific glutathione, rather than decreased ascorbate contents, could
      be correlated with the development of symptoms in these mutants suggesting that
      higher sensitivity to Cd is related to low glutathione contents rather than low
      ascorbate contents. On the subcellular level it became obvious that long-term
      treatment of wildtype plants with Cd induced the depletion of glutathione and
      ascorbate contents in all cell compartments except chloroplasts indicating an
      important protective role for antioxidants in chloroplasts against Cd.
      Additionally, we could observe an immediate decrease of glutathione and ascorbate
      in all cell compartments 12 h after Cd treatment indicating that glutathione and
      ascorbate are either withdrawn from or not redistributed into other organelles
      after their production in chloroplasts, cytosol (production centers for
      glutathione) and mitochondria (production center for ascorbate). The obtained
      data is discussed in respect to recently proposed stress models involving
      antioxidants in the protection of plants against environmental stress conditions.

PMID- 24281835
TI  - Dirhodium(II) carboxylate catalyzed formation of 1,2,3-trisubstituted indoles
      from styryl azides.
AB  - Dirhodium(II)-carboxylate complexes were discovered to promote the selective
      migration of acyl groups in trisubstituted styryl azides to form 1,2,3
      trisubstituted indoles. The styryl azides are readily available in three steps
      from cyclobutanone and 2-iodoaniline. 

PMID- 24281836
TI  - Malaria infection alters the expression of hepatobiliary and placental drug
      transporters in pregnant mice.
AB  - Preventing and treating malaria in pregnancy is a global health priority. However
      little is known regarding the impact of malaria infection on the maternal and
      fetal disposition of pharmaceuticals and other xenobiotics. Our objective was to
      characterize expression of key determinants of drug-disposition in maternal and
      fetal tissues in a validated murine model of experimental placental malaria.
      Balb/c mice were infected with Plasmodium berghei at mid gestation [gestational
      day (GD) 13] and maternal, placental, and fetal tissues were collected at GD19.
      Expression of key ABC drug transporters and Cyp3a11 was examined by quantitative
      polymerase chain reaction. Western blotting was used to examine the protein
      expression of multidrug resistance protein 1 (MDR1, ABCB1). Compared with
      controls, placental mRNA expression of Abcb1a, Abcb1b, Abcc1, Abcc2, Abcc3, and
      Abcg2 were significantly downregulated in the malaria-infected group (P < 0.05),
      as was placental MDR1 protein (P < 0.05). Significantly decreased hepatic
      expression of Abcc2, Abcg2, and Abcb11 and significantly increased expression of
      Abcb1b, Abcc1, and Abcc3 were seen in malaria-infected dams (P < 0.05) in
      comparison with uninfected controls. The expression of Abcb1a and Abcg2 was
      significantly decreased in fetal liver of infected dams, whereas levels of Abcb1b
      were increased (P < 0.05). Maternal and fetal hepatic expression of Cyp3a11 was
      significantly downregulated in the malaria group (P < 0.05). Together, malaria
      induced alterations in the expression of transporters and drug-metabolizing
      enzymes in maternal and fetal tissues may alter the disposition of endogenous and
      therapeutic substrates, potentially impacting maternal and fetal outcomes. 

PMID- 24281838
TI  - Palladium monophosphine Pd(PPh3): is it really accessible in solution?
AB  - Catalyst speciation is a ubiquitous theme in homogeneous catalysis. Employing
      realistic models based on an explicit solvent representation and ab initio
      molecular dynamics simulations we addressed the issue of solvent coordination in
      the Pd-PPh3 system. We show the accessibility of species such as (Sol)Pd(PPh3),
      (Sol)Pd(PPh3)2, (Sol)2Pd(PPh3) (where Sol is a solvent molecule). Importantly, we
      demonstrate that the bare monophosphine Pd(PPh3) species, often depicted in
      catalytic cycles, is actually not accessible in solution. 

PMID- 24281837
TI  - Inducible gene deletion in the entire cardiac conduction system using Hcn4
      CreERT2 BAC transgenic mice.
AB  - Developmental defects and disruption of molecular pathways of the cardiac
      conduction system (CCS) can cause life-threatening cardiac arrhythmias. Despite
      decades of effort, knowledge about the development and molecular control of the
      CCS remains primitive. Mouse genetics, complementary to other approaches such as
      human genetics, has become a key tool for exploring the developmental processes
      of various organs and associated diseases. Genetic analysis using mouse models
      will likely provide great insights about the development of the CCS, which can
      facilitate the development of novel therapeutic strategies to treat arrhythmias.
      To enable genetic studies of the CCS, CCS-associated Cre mouse models are
      essential. However, existing mouse models with Cre activity reported in the CCS
      have various limitations such as Cre leak, haploinsufficiency, and inadequate
      specificity of the Cre activity. To circumvent those limitations, we successfully
      generated Hcn4-CreERT2 bacterial artificial chromosome (BAC) transgenic mice
      using BAC recombineering in which Cre activity was specifically detected in the
      entire CCS after tamoxifen induction. Our Hcn4-CreERT2 BAC transgenic line will
      be an invaluable genetic tool with which to dissect the developmental control of
      CCS and arrhythmias.

PMID- 24281839
TI  - Comparative study of photochromic ferrocene-conjugated dimethyldihydropyrene
      derivatives.
AB  - The photochemical properties and the mixed-valence state of
      bis(ferrocenylethynyl)benzodimethyldihydropyrene (1) and other
      benzodimethyldihydropyrene (BzDHP) derivatives were investigated to understand
      the reversible photoswitching in the electronic communication of 1. Absorption
      spectra of 1 were characterized by UV/Vis spectroscopy and calculated by using
      time-dependent density functional theory (TD-DFT), and the d orbitals of the
      ferrocene (Fc) moieties were shown to contribute to the occupied valence orbitals
      that were responsible for the photochromic behavior. 1 exhibited reversible
      photoisomerization in THF; however, photochromic behavior was not observed in
      dichloromethane. Analysis of redox potentials showed that the mixed-valence state
      of 1 was more stable in dichloromethane than in THF. This is consistent with the
      observation that chemical oxidation led to an intervalence charge-transfer (IVCT)
      band between the Fc moieties in the mixed-valence state of 1 in dichloromethane,
      whereas such a band was not observed for one-electron-oxidized 1 in THF.
      Bis(pentamethylferrocenylethynyl)benzodimethyldihydropyrene (2) did not show
      photochromic behavior even in THF. The mixed-valence state of 2 was much less
      stable than that of 1 in dichloromethane, and no obvious IVCT band was observed
      for one-electron-oxidized 2 in dichloromethane. The difference in the redox
      contribution of Fc and pentamethylferrocene (Me5Fc) to BzDHP played an important
      role for these redox and photochromic behaviors; this was supported by analysis
      of valence orbital energies from DFT calculations. Designing molecules that
      connect redox centers through the use of a photochromic linker with a redox
      potential close to that of the redox centers could constitute a useful approach
      for the production of photochromic redox-active metal complexes with strong
      electronic communication.

PMID- 24281840
TI  - Life on the edge: thermal optima for aerobic scope of equatorial reef fishes are
      close to current day temperatures.
AB  - Equatorial populations of marine species are predicted to be most impacted by
      global warming because they could be adapted to a narrow range of temperatures in
      their local environment. We investigated the thermal range at which aerobic
      metabolic performance is optimum in equatorial populations of coral reef fish in
      northern Papua New Guinea. Four species of damselfishes and two species of
      cardinal fishes were held for 14 days at 29, 31, 33, and 34  degrees C, which
      incorporated their existing thermal range (29-31  degrees C) as well as projected
      increases in ocean surface temperatures of up to 3  degrees C by the end of this
      century. Resting and maximum oxygen consumption rates were measured for each
      species at each temperature and used to calculate the thermal reaction norm of
      aerobic scope. Our results indicate that one of the six species, Chromis
      atripectoralis, is already living above its thermal optimum of 29  degrees C. The
      other five species appeared to be living close to their thermal optima (ca. 31 
      degrees C). Aerobic scope was significantly reduced in all species, and
      approached zero for two species at 3  degrees C above current-day temperatures.
      One species was unable to survive even short-term exposure to 34  degrees C. Our
      results indicate that low-latitude reef fish populations are living close to
      their thermal optima and may be more sensitive to ocean warming than higher
      latitude populations. Even relatively small temperature increases (2-3  degrees
      C) could result in population declines and potentially redistribution of
      equatorial species to higher latitudes if adaptation cannot keep pace. 

PMID- 24281841
TI  - The effect of bovine colostrum supplementation in older adults during resistance
      training.
AB  - Bovine colostrum is the first milk secreted by cows after parturition and has
      high levels of protein, immunoglobulins, and various growth factors. We
      determined the effects of 8 weeks of bovine colostrum supplementation versus whey
      protein during resistance training in older adults. Males (N = 15, 59.1 +/- 5.4
      y) and females (N = 25, 59.0 +/- 6.7 y) randomly received (double-blind) 60 g/d
      of colostrum or whey protein complex (containing 38 g protein) while
      participating in a resistance training program (12 exercises, 3 sets of 8-12
      reps, 3 days/ week). Strength (bench press and leg press 1-RM), body composition
      (by dual energy x-ray absorptiometry), muscle thickness of the biceps and
      quadriceps (by ultrasound), cognitive function (by questionnaire), plasma insulin
      like growth factor-1 (IGF-1) and C-reactive protein (CRP, as a marker of
      inflammation), and urinary N-telopeptides (Ntx, a marker of bone resorption) were
      determined before and after the intervention. Participants on colostrum increased
      leg press strength (24 +/- 29 kg; p < .01) to a greater extent than participants
      on whey protein (8 +/- 16 kg) and had a greater reduction in Ntx compared with
      participants on whey protein (-15 +/- 40% vs. 10 +/- 42%; p < .05). Bench press
      strength, muscle thickness, lean tissue mass, bone mineral content, and cognitive
      scores increased over time (p < .05) with no difference between groups. There
      were no changes in IGF-1 or CRP. Colostrum supplementation during resistance
      training was beneficial for increasing leg press strength and reducing bone
      resorption in older adults. Both colostrum and whey protein groups improved upper
      body strength, muscle thickness, lean tissue mass, and cognitive function.

PMID- 24281843
TI  - Dopamine-loaded poly(D,L-lactic-co-glycolic acid) microspheres: new strategy for
      encapsulating small hydrophilic drugs with high efficiency.
AB  - The effective controlled release of small hydrophilic drugs from poly(d,l-lactic
      co-glycolic acid) (PLGA) microspheres has remained a challenge, largely due to
      the difficulty of loading a large amount of the drug inside the microspheres,
      owing to the hydrophilicity of the drugs. This study provides a new strategy for
      increasing encapsulation of small hydrophilic drugs inside PLGA microspheres by
      utilizing noncovalent, physical adsorption between hydrophilic drugs and
      emulsifying polymers of poly(vinyl alcohol) and pluronic. An order of magnitude
      increase in drug loading efficiency from 2.7 to 18.6% for dopamine, a model small
      hydrophilic drug, was achieved. The large amount of dopamine-loaded PLGA
      formulation herein could be useful for the treatment of Parkinson's disease.

PMID- 24281842
TI  - Biomarker modelling of early molecular changes in Alzheimer's disease.
AB  - The preclinical phase of Alzheimer's disease (AD) occurs years, possibly decades,
      before the onset of clinical symptoms. Being able to detect the very earliest
      stages of AD is critical to improving understanding of AD biology, and
      identifying individuals at greatest risk of developing clinical symptoms with a
      view to treating AD pathophysiology before irreversible neurodegeneration occurs.
      Studies of dominantly inherited AD families and longitudinal studies of sporadic
      AD have contributed to knowledge of the earliest AD biomarkers. Here we appraise
      this evidence before reviewing novel, particularly fluid, biomarkers that may
      provide insights into AD pathogenesis and relate these to existing hypothetical
      disease models. 

PMID- 24281844
TI  - Shape readout of AT-rich DNA by carbohydrates.
AB  - Gene expression can be altered by small molecules that target DNA; sequence as
      well as shape selectivities are both extremely important for DNA recognition by
      intercalating and groove-binding ligands. We have characterized a carbohydrate
      scaffold (1) exhibiting DNA "shape readout" properties. Thermodynamic studies
      with 1 and model duplex DNAs demonstrate the molecule's high affinity and
      selectivity towards B* form (continuous AT-rich) DNA. Isothermal titration
      calorimetry (ITC), circular dichroism (CD) titration, ultraviolet (UV) thermal
      denaturation, and Differential Scanning Calorimetry were used to characterize the
      binding of 1 with a B* form AT-rich DNA duplex d[5'-G2 A6 T6 C2 -3']. The binding
      constant was determined using ITC at various temperatures, salt concentrations,
      and pH. ITC titrations were fit using a two-binding site model. The first binding
      event was shown to have a 1:1 binding stoichiometry and was predominantly entropy
      driven with a binding constant of approximately 10(8) M(-1) . ITC-derived binding
      enthalpies were used to obtain the binding-induced change in heat capacity
      (DeltaCp ) of -225 +/- 19 cal/mol.K. The ionic strength dependence of the binding
      constant indicated a significant electrolytic contribution in ligand:DNA binding,
      with approximately four to five ion pairs involved in binding. Ligand 1 displayed
      a significantly higher affinity towards AT-tract DNA over sequences containing GC
      inserts, and binding experiments revealed the order of binding affinity for 1
      with DNA duplexes: contiguous B* form AT-rich DNA (d[5'-G2 A6 T6 C2 -3']) >B form
      alternate AT-rich DNA (d[5'-G2 (AT)6 C2- 3']) > A form GC-rich DNA (d[5'-A2 G6 C6
      T2 -3']), demonstrating the preference of ligand 1 for B* form DNA.

PMID- 24281845
TI  - Intraoperative neural monitoring in thyroid cancer surgery.
AB  - BACKGROUND: Intraoperative neural monitoring (IONM) has increasingly garnered the
      attention of the surgeons performing thyroid and parathyroid surgery around the
      world. Current studies suggest a majority of general and head and neck surgeons
      utilize neural monitoring in their thyroid surgical case load in both the US and
      Germany. PURPOSE: We aim to present an up-to-date review of the application of
      IONM specifically focusing on its utility in thyroid cancer surgery. Neural
      monitoring is discussed particularly as it relates to neural prognosis, the
      issues of staged thyroid surgery for thyroid cancer, and new horizons in the
      monitoring of the superior laryngeal nerve (SLN) and prevention of neural injury
      through continuous vagal neural monitoring. CONCLUSION: IONM, as it relates to
      thyroid surgery, has obtained a widespread acceptance as an adjunct to the gold
      standard of visual nerve identification. The value of IONM in prognosticating
      neural function and in intraoperative decision making regarding proceeding to
      bilateral surgery is also well-known. Initial data on recent extensions of IONM
      in the form of SLN monitoring and continuous vagal nerve monitoring are
      promising. Continuous vagal nerve monitoring expands the utility of IONM by
      providing real-time electrophysiological information, allowing surgeons to take a
      corrective action in impending neural injury.

PMID- 24281846
TI  - Multiplexed and data-independent tandem mass spectrometry for global proteome
      profiling.
AB  - One of the most important early developments in the field of proteomics was the
      advent of automated data acquisition routines that allowed high-throughput
      unattended data acquisition during HPLC introduction of peptide mixtures to a
      tandem mass spectrometer. Prior to this, data acquisition was orders of magnitude
      less efficient being based entirely on lists of predetermined ions generated in a
      prior HPLC-MS experiment. This process, known generically as data-dependent
      analysis, empowered the development of shotgun proteomics where hundreds to
      thousands of peptide sequences are matched per experiment. In their most popular
      implementation, the most abundant ionized species from every precursor ion scan
      at each moment in chromatographic time are successively selected for isolation,
      activation and tandem mass analysis. While extremely powerful, this strategy has
      one primary limitation in that detectable dynamic range is restricted (in a top
      down manner) to the peptides that ionize the best. To circumvent the serial
      nature of the data-dependent process and increase detectable dynamic range, the
      concepts of multiplexed and data-independent acquisition (DIA) have emerged.
      Multiplexed-data acquisition is based on more efficient co-selection and co
      dissociation of multiple precursor ions in parallel, the data from which is
      subsequently de-convoluted to provide polypeptide sequences for each individual
      precursor ion. DIA has similar goals, but there is no real-time ion selection
      based on prior precursor ion scans. Instead, predefined m/z ranges are
      interrogated either by fragmenting all ions entering the mass spectrometer at
      every single point in chromatographic time; or by dividing the m/z range into
      smaller m/z ranges for isolation and fragmentation. These approaches aim to fully
      utilize the capabilities of mass spectrometers to maximize tandem MS acquisition
      time and to address the need to expand the detectable dynamic range, lower the
      limit of detection, and improve the overall confidence of peptide identifications
      and relative protein quantification measurements. This review covers all aspects
      of multiplexed- and data-independent tandem mass spectrometry in proteomics, from
      experimental implementations to advances in software for data interpretation.

PMID- 24281847
TI  - High-yield electrochemical production of formaldehyde from CO2 and seawater.
AB  - The catalytic, electrocatalytic, or photocatalytic conversion of CO2 into useful
      chemicals in high yield for industrial applications has so far proven difficult.
      Herein, we present our work on the electrochemical reduction of CO2 in seawater
      using a boron-doped diamond (BDD) electrode under ambient conditions to produce
      formaldehyde. This method overcomes the usual limitation of the low yield of
      higher-order products, and also reduces the generation of H2 . In comparison with
      other electrode materials, BDD electrodes have a wide potential window and high
      electrochemical stability, and, moreover, exhibit very high Faradaic efficiency
      (74%) for the production of formaldehyde, using either methanol, aqueous NaCl, or
      seawater as the electrolyte. The high Faradaic efficiency is attributed to the
      sp(3)-bonded carbon of the BDD. Our results have wide ranging implications for
      the efficient and cost-effective conversion of CO2.

PMID- 24281848
TI  - The relationship between parental stress and postpartum depression among
      adolescent mothers enrolled in a randomized controlled prevention trial.
AB  - Given the high co-occurrence of depression and parental stress among adolescent
      mothers, we evaluated the relationship between parental stress and postpartum
      depression among primiparous adolescent mothers. We conducted an observational
      analysis among a cohort of 106 adolescent mothers at 289 postpartum visits who
      were enrolled in a randomized controlled trial to prevent postpartum depression.
      Parental stress was measured using the Parenting Stress Index, short form. The
      Structured Clinical Interview for DSM-IV Childhood Diagnoses was administered to
      assess for postpartum depression; subthreshold depression was assessed using the
      Children's Depression Rating Scale, revised version. Generalized estimating
      equations were utilized to assess the relationship of parental stress on
      postpartum depression during the first 6 months postpartum. We present adjusted
      odds ratios (AOR) controlling for study arm, age, born in the United States,
      prior history of depression, and number of study visits. The median age was 16
      years, 53% were Latina, and 16% reported a past history of depression. Nineteen
      adolescents (19%) were diagnosed with postpartum depression and 25% experienced
      high levels of parental stress through 6 months postpartum. Adolescent mothers
      who reported higher levels of parental stress were at significantly increased
      risk for postpartum depression [AOR 1.06 (95% CI 1.04-1.09); p < 0.0001]. High
      levels of parental stress predicted subsequent postpartum depression when
      assessing parental stress at visits prior to a depression diagnosis to determine
      whether we could establish a temporal association [AOR 1.06 (95% CI 1.02-1.09); p
      < 0.01]. Parental stress was also a risk factor for subthreshold depression [AOR
      1.04 (95% CI 1.01-1.07); p < 0.01]. Parental stress was a significant risk factor
      for developing both postpartum depression as well as subthreshold depression
      among adolescent mothers. Interventions that target a reduction in parental
      stress may lead to less depression severity among primiparous adolescent mothers.

PMID- 24281849
TI  - Comparison of prospective and retrospective measurements of frequency of sexual
      intercourse.
AB  - Measurements of sexual intercourse frequency are informative for research on
      pregnancy, contraception, and the transmission of sexually transmitted
      infections; however, efficiently collecting data on this sensitive topic is
      complex. The purpose of this study was to determine whether retrospective recall
      of sexual intercourse frequency was consistent with information obtained through
      the use of prospective daily diary methods corresponding to the same time period
      in a diverse sample of women. A total of 185 women participated in a
      longitudinal, prospective cohort study of oral contraceptive users and 98 of
      these women provided complete information on sexual intercourse frequency on
      diaries (prospective) and postcards (retrospective). Linear mixed models were
      used to test for variation in response within categories of demographic and other
      variables. The mean number of days women had sexual intercourse per week was 1.5
      days using prospective diary information versus 2.0 days when using 3-month
      retrospective recall (p < 0.001). Mean differences for the various
      sociodemographic subgroups were positive for all groups indicating that women
      consistently reported a higher frequency of sexual intercourse on the
      retrospective postcards than they recorded on their prospective diaries; however,
      these mean differences did not vary significantly. If confirmed in other samples,
      the use of retrospective methods may be adequate to accurately collect data on
      sexual intercourse frequency-and may be preferable. Using only retrospective
      measurements could decrease study costs, the burden to participants, and have a
      higher response rate.

PMID- 24281850
TI  - The impact of community health professional contact postpartum on breastfeeding
      at 3 months: a cross-sectional retrospective study.
AB  - This study investigated the effect of any health professional contact and the
      types of contact new mothers received in the first 10 days post-discharge on
      breastfeeding rates at 3 months. This cross-sectional retrospective self-report
      survey was distributed to women who birthed in Queensland, Australia between 1st
      February and 31st May 2010 at 4-5 months postpartum. Data were collected on
      pregnancy, birth, postpartum care and infant feeding. Logistic regression was
      used to assess the relationship between health professional contact and
      breastfeeding at 3 months. Data were analysed by birthing facility sector because
      of significant differences between sectors in health professional contact. The
      study cohort consisted of 6,852 women. Women in the public sector were more
      likely to be visited at home than women birthing in the private sector. Any
      health professional contact (AOR 1.65 99 % CI 0.98-2.76 public sector, AOR 0.78
      99 % CI 0.59-1.03 private sector) and home visits (AOR 1.50 99 % CI 0.89-2.54
      public sector, AOR 0.80 99 % CI 0.46-1.39 private sector) were not associated
      with breastfeeding at 3 months in either sector. A telephone call (AOR 2.07 99 %
      CI 1.06-4.03) or visit to a general practitioner (GP) (AOR 1.83 99 % CI 1.04
      3.21) increased the odds of breastfeeding in public sector women. Health
      professional contact or home visiting in the first 10 days post-discharge did not
      have a significant impact on breastfeeding rates at 3 months. Post-discharge
      telephone contact for all women and opportunities for self-initiated clinic
      visits for women assessed to be at higher risk of ceasing breastfeeding may be
      the most effective care. 

PMID- 24281851
TI  - Impairment of emotional facial expression and prosody discrimination due to
      ischemic cerebellar lesions.
AB  - A growing literature points to a specific role of the cerebellum in affect
      processing. However, understanding of affect processing disturbances following
      discrete cerebellar lesions is limited. We administered the Tubingen Affect
      Battery to assess recognition of emotional facial expression and emotional
      prosody in 15 patients with a cerebellar infarction and 10 age-matched controls.
      On emotional facial expression tasks, patients compared to controls showed
      impaired selection and matching of facial affect. On prosody tasks, patients
      showed marked impairments in naming affect and discriminating incongruencies.
      These deficits were more pronounced for negative affects. Our results confirm a
      significant role of the cerebellum in processing emotional recognition, a
      component of social cognition. 

PMID- 24281852
TI  - Genetic variation in multiple biologic pathways, flavonoid intake, and breast
      cancer.
AB  - PURPOSE: We previously reported an inverse association between flavonoid intake
      and breast cancer incidence, which has been confirmed by others, but no studies
      have considered simultaneously potential interactions of flavonoids with multiple
      genetic polymorphisms involved in biologically relevant pathways (oxidative
      stress, carcinogen metabolism, DNA repair, and one-carbon metabolism). METHODS:
      To estimate interaction effects between flavonoids and 13 polymorphisms in these
      four pathways on breast cancer risk, we used population-based data (n = 875 cases
      and 903 controls) and several statistical approaches, including conventional
      logistic regression and semi-Bayesian hierarchical modeling (incorporating prior
      information on the possible biologic functions of genes), which also provides
      biologic pathway-specific effect estimates. RESULTS: Compared to the standard
      multivariate model, the results from the hierarchical model indicate that gene-by
      flavonoid interaction estimates are attenuated, but more precise. In the
      hierarchical model, the average effect of the deleterious versus beneficial gene,
      controlling for average flavonoid intake in the DNA repair pathway, and adjusted
      for the three other biologically relevant pathways (oxidative stress, carcinogen
      metabolism, and one-carbon metabolism), resulted in a 27 % increase risk for
      breast cancer [odds ratio = 1.27; 95 % confidence interval (CI) = 0.70, 2.29].
      However, the CI was wide. CONCLUSIONS: Based on results from the semi-Bayesian
      model, breast cancer risk may be influenced jointly by flavonoid intake and genes
      involved in DNA repair, but our findings require confirmation.

PMID- 24281853
TI  - Wound infections following open reduction and internal fixation of calcaneal
      fractures with an extended lateral approach.
AB  - PURPOSE: Post-operative wound infections (PWI) following calcaneal fracture
      surgery can lead to prolonged hospital stay and additional treatment with
      antibiotics, surgical debridement or implant removal. Our aim was to determine
      the incidence of superficial and deep PWI and to identify risk factors (RF).
      METHODS: This study is a retrospective case series. All consecutive patients from
      2000 to 2010 with a closed unilateral calcaneal fracture treated with open
      reduction and internal fixation (ORIF) by an extended lateral approach were
      included. Patient, fracture, trauma and peri-operative characteristics were
      collected, including RF such as smoking, diabetes mellitus, time to operation,
      pre-operative in- or outpatient management and wound closure technique. The
      primary end point was a PWI as defined by the US Centers for Disease Control and
      Prevention. RESULTS: A total of 191 patients were included of which 47 patients
      (24.6%) had a PWI; 21 (11.0%) and 26 (13.6%) patients had a superficial and deep
      wound infection, respectively. American Society of Anesthesiologists (ASA)
      classification higher than ASA 1 was associated with an increased risk. Placement
      of a closed suction drain at the end of surgery was associated with less PWI (35%
      vs 15%, p = 0.002). In this study, none of the previously reported RF were
      associated with an increased risk for PWI. CONCLUSIONS: ORIF of displaced
      calcaneal fractures is associated with a high rate of PWI of 25%. Factors that
      were associated with an increased risk were ASA classification other than 1 and
      absence of a closed suction drain placement. A closed suction drain may be a
      protective measure to avoid wound complications.

PMID- 24281854
TI  - GdDO3NI, a nitroimidazole-based T1 MRI contrast agent for imaging tumor hypoxia
      in vivo.
AB  - Tumor hypoxia is known to affect sensitivity to radiotherapy and promote
      development of metastases; therefore, the ability to image tumor hypoxia in vivo
      could provide useful prognostic information and help tailor therapy. We
      previously demonstrated in vitro evidence for selective accumulation of a
      gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2
      nitroimidazole (GdDO3NI), a magnetic resonance imaging T1-shortening agent, in
      hypoxic cells grown in tissue culture. We now report evidence for accumulation of
      GdDO3NI in hypoxic tumor tissue in vivo. Our data show that GdDO3NI accumulated
      significantly (p < 0.05) in the central, poorly perfused regions of rat prostate
      adenocarcinoma AT1 tumors (threefold higher concentration than for the control
      agent) and showed better clearance from well-perfused regions and complete
      clearance from the surrounding muscle tissue. Inductively coupled plasma mass
      spectroscopy confirmed that more GdDO3NI than control agent was retained in the
      central region and that more GdDO3NI was retained in the central region than at
      the periphery. These results show the utility of GdDO3NI to image tumor hypoxia
      and highlight the potential of GdDO3NI for application to image-guided
      interventions for radiation therapy or hypoxia-activated chemotherapy.

PMID- 24281855
TI  - Peroxomanganese complexes as an aid to understanding redox-active manganese
      enzymes.
AB  - Over the past 7 years, there have been a significant number of studies describing
      the structural and electronic properties, as well as the chemical reactivity, of
      synthetic peroxomanganese adducts. Many redox-active manganese enzymes, including
      manganese-containing superoxide dismutases, extradiol catechol dioxygenases, and
      ribonucleotide reductases, are proposed to feature peroxomanganese intermediates
      in their catalytic cycles. The recent efforts to model these intermediates using
      synthetic complexes have thus provided a strong complement to mechanistic studies
      of the enzymes. This review provides both a summary and a perspective of work in
      this area, with an emphasis on the relationship between geometric and electronic
      structure and chemical reactivity for eta(2)-peroxomanganese(III) and eta(1)
      alkylperoxomanganese(III) adducts. 

PMID- 24281856
TI  - Stage-specific quantitative changes in renal and urinary proteome during the
      progression and development of streptozotocin-induced diabetic nephropathy in
      rats.
AB  - Diabetic nephropathy (DN) is a microvascular complication associated with
      diabetes causing slow deterioration of kidneys leading to end-stage renal
      disease. Timely intervention and diagnosis are crucial in order to ameliorate and
      halt the progression of DN. Current diagnosis of DN consists of urine assays for
      detection of microalbuminuria, which have inadequate specificity and sensitivity.
      Hence, there arises a need to discover stage-specific biomarkers which can aid in
      the early detection of DN and also in identifying the mechanisms underlying
      pathogenesis of DN. Therefore the present study was undertaken to identify the
      differentially expressed proteins in the urine and to examine the pattern of
      proteomic changes occurring in the rat kidneys during the course of progression
      of streptozotocin-induced model of DN in rats. Two-dimensional gel
      electrophoresis coupled to MALDI-TOF mass spectrometry was employed to identify
      the differentially expressed proteins under diabetic conditions. Among the
      identified proteins Calgranulin A and Calgranulin B appeared in the urinary
      proteome at the fourth week of induction of diabetes while we recorded a time
      dependent decrease in the expression of major urinary protein (alpha 2u globulin)
      in the urine as well as kidneys of diabetic rats. Parallel monitoring of targeted
      proteomic changes in the renal proteome revealed an increase in histone H2B
      phosphorylation at serine14 along with a gradual decrease in Bcl-2 and MMP-13
      expression during the course of progression and development of streptozotocin
      induced DN. 

PMID- 24281857
TI  - Combined incubation of colon carcinoma cells with phorbol ester and mitochondrial
      uncoupling agents results in synergic elevated reactive oxygen species levels and
      increased gamma-glutamyltransferase expression.
AB  - The NADPH oxidase (NOX) is a significant determinant for the expression and
      activity of gamma-glutamyltransferase (GGT), which is frequently upregulated
      after increased levels of reactive oxygen species (ROS) and oxidative stress.
      Earlier studies on human colon carcinoma HT-29 cells have shown that treatment
      with phorbol 12-myristate 13-acetate (PMA) activates NOX thus increasing the
      intracellular level of ROS and upregulating GGT. Another important source of
      cellular ROS is the mitochondria, and treatment with the mitochondria uncoupler
      carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP) results in increased
      ROS levels. The present study shows that when HT-29 cells were simultaneously
      treated with both agents, a significant and synergic increase in intracellular
      ROS was detected. NOX activity contributed at least 50 % of this increase as
      inhibiting NOX activity with apocynin or downregulating the NOX activity using
      siRNA against p22 phox reduced the synergic ROS production. The combined FCCP and
      PMA treatment also provoked highly increased GGT mRNA levels after 24 h whereas
      only minor and delayed increases in GGT protein and enzyme activity levels were
      detected. The results strongly indicate that ROS production by both mitochondria
      and NOX is involved in the regulation of GGT expression in colon carcinoma cells.

PMID- 24281859
TI  - Kinship: born and bred (but also facilitated)? A commentary on 'Donor conception:
      ethical aspects of information sharing' (Nuffield Council on Bioethics, London
      2013).

PMID- 24281860
TI  - Non-activated protein C rescue treatment in Wilms tumour associated hepatic
      sinusoidal obstructive syndrome.
AB  - Hepatic sinusoidal obstructive syndrome (HSOS) is a frequent complication in
      patients undergoing haematopoietic stem cell transplant (HSCT), and more rarely,
      in paediatric patients receiving conventional chemotherapy for solid tumours. Its
      diagnosis relies on a combination of clinical signs and symptoms such as
      hepatomegaly, jaundice, weight gain and fluid retention. HSOS treatment is
      primarily based on supportive care and anti-fibrinolytic agents. Here we report
      two patients affected by Wilms tumour who developed life-threatening HSOS that
      failed to respond to conventional treatment. Both patients recovered after
      receiving aggressive supportive treatment that included administration of non
      activated protein C (Ceprotin(r)--Baxter).

PMID- 24281858
TI  - Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2
      dimethyl hydrazine-induced colon tumorigenesis in Wistar rats.
AB  - Colon cancer remains one of the major worldwide causes of cancer-related
      morbidity and mortality in Western countries and is increasingly common in Asia.
      Ellagic acid (EA), a major component of polyphenol possesses attractive remedial
      features. The aim of this study is to divulge the potential effect of EA during
      1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The
      rats were segregated into four groups: group I, control rats; group II, rats
      received EA (60 mg/kg b.wt./day, orally); rats in group III, induced with DMH (20
      mg/kg b.wt.) subcutaneously for 15 weeks; DMH-induced group IV rats were
      initiated with EA treatment. Colon of the rats treated with DMH exhibited higher
      glycoconjugates and proliferation index such as elevated expressions of
      argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear
      antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells.
      DMH induction also increased phase I-metabolizing enzymes with simultaneous
      decrease in the phase II detoxifying enzymes. In contrast, dietary administration
      of EA significantly (p < 0.05) down regulated the proliferation index and
      restored back the levels of biotransformation enzymes. The carcinogenic insult
      also altered the expression of pro-apoptotic protein p53, whereas dietary EA
      administration significantly (p < 0.01) up regulates p53 expression to further
      induce apoptotic pathway. Ultrastructural changes in colon were also in accord
      with the above aberrations. Overall findings suggested that the suppression of
      colon cancer by EA in vivo involves inhibition of cell proliferation, activation
      of apoptosis, and efficient detoxification. 

PMID- 24281861
TI  - A consensus on concussion: While there is agreement on guidelines, there are gaps
      in awareness and education.

PMID- 24281865
TI  - Transgene delivery to cultured keratinocytes via replication-deficient adenovirus
      vectors.
AB  - Transient transgene expression can facilitate investigation of that gene-product
      function or effect on keratinocyte biology. Several chemical and biologic
      delivery systems are available, and among them adenoviruses offer particular
      advantages in efficiency and transgene capacity. Here we describe the advantages
      of bicistronic adenovirus and inclusion of the polycation hexadimethrine bromide
      to aid in the detection of positively transduced cells and enhance transduction
      efficiency. 

PMID- 24281866
TI  - MMP-2, -9 and TIMP-1, -2 assays in keratinocyte cultures.
AB  - To determine the status of tissue metabolism in the epidermis, matrix
      metalloproteinase (MMP)-2 and -9 and tissue inhibitor of metalloproteinases
      (TIMP)-1 and -2 can be detected using keratinocytes in culture. In addition to
      Western blotting analysis, gelatin zymography for MMP-2 and -9 and the reverse
      zymography for TIMP-1 and -2 are useful methods for evaluating such protein
      expressions both qualitatively and quantitatively, because MMP-2 and MMP-9 are
      known as gelatinase. Moreover, real-time analysis for zymography can be performed
      using fluorescein isothiocyanate-labelled gelatin.

PMID- 24281867
TI  - A novel three-dimensional cell culture method to analyze epidermal cell
      differentiation in vitro.
AB  - Studies of the epidermis have been carried out in various models, such as the
      monolayer culture in vitro model and three-dimensional (3D) skin models, that are
      spatially organized to display the architectural features seen in human skin.
      These models have furthered our understanding of epidermal cell biology and
      provided quite a few lines of evidence on proliferation, cellular metabolism,
      morphological status, and state of differentiation. In this chapter, we describe
      a novel method using epithelial cell aggregates embedded in a collagen gel,
      instead of individual cells, for building cell-cell and cell-matrix interactions.
      Analyzing cell behaviors during epidermal differentiation would be helpful. Our
      method would help to analyze a possible regulatory mechanism underlying epidermal
      differentiation. 

PMID- 24281864
TI  - Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue
      specific and systemic functions.
AB  - NCX proteins explore the electrochemical gradient of Na(+) to mediate Ca(2+)
      fluxes in exchange with Na(+) either in the Ca(2+)-efflux (forward) or Ca(2+)
      influx (reverse) mode, whereas the directionality depends on ionic concentrations
      and membrane potential. Mammalian NCX variants (NCX1-3) and their splice variants
      are expressed in a tissue-specific manner to modulate the heartbeat rate and
      contractile force, the brain's long-term potentiation and learning, blood
      pressure, renal Ca(2+) reabsorption, the immune response, neurotransmitter and
      insulin secretion, apoptosis and proliferation, mitochondrial bioenergetics, etc.
      Although the forward mode of NCX represents a major physiological module, a
      transient reversal of NCX may contribute to EC-coupling, vascular constriction,
      and synaptic transmission. Notably, the reverse mode of NCX becomes predominant
      in pathological settings. Since the expression levels of NCX variants are disease
      related, the selective pharmacological targeting of tissue-specific NCX variants
      could be beneficial, thereby representing a challenge. Recent structural and
      biophysical studies revealed a common module for decoding the Ca(2+)-induced
      allosteric signal in eukaryotic NCX variants, although the phenotype variances in
      response to regulatory Ca(2+) remain unclear. The breakthrough discovery of the
      archaebacterial NCX structure may serve as a template for eukaryotic NCX,
      although the turnover rates of the transport cycle may differ ~10(3)-fold among
      NCX variants to fulfill the physiological demands for the Ca(2+) flux rates.
      Further elucidation of ion-transport and regulatory mechanisms may lead to
      selective pharmacological targeting of NCX variants under disease conditions.

PMID- 24281868
TI  - Differentiation of epidermal keratinocytes from human embryonic stem cells.
AB  - For many years, cell therapies have been hampered by limited availability and
      inter-batch variability of primary cells. Human embryonic stem cell (hESC) can
      give rise to specialized cells like keratinocytes and recently emerged as a
      virtually unlimited source of potential therapeutic cells. However, xenogeneic
      components in differentiation cocktails have been limiting the clinical potential
      of hESC-derived keratinocytes (hESCs-Kert). Here, we demonstrated efficient
      differentiation of H9 human embryonic stem cells (H9-hESCs) into keratinocytes
      (H9-Kert(ACC)) in an autogenic co-culture system. We used activin as the main
      factor to induce keratinocyte differentiation. H9-Kert(ACC) expressed
      keratinocyte markers at mRNA and protein levels. Establishment of such animal
      free microenvironment for keratinocyte differentiation will accelerate potential
      clinical application of hESCs.

PMID- 24281869
TI  - Modified methods for growing 3-D skin equivalents: an update.
AB  - Artificial epidermis can be reconstituted in vitro by seeding primary epidermal
      cells (keratinocytes) onto a supportive substrate and then growing the developing
      skin equivalent at the air-liquid interface. In vitro skin models are widely used
      to study skin biology and for industrial drug and cosmetic testing. Here, we
      describe updated methods for growing 3-dimensional skin equivalents using de
      vitalized, de-epidermalized dermis (DED) substrates including methods for DED
      substrate preparation, cell seeding, growth conditions, and fixation procedures.

PMID- 24281870
TI  - Microdissection and visualization of individual hair follicles for lineage
      tracing studies.
AB  - In vivo lineage tracing is a valuable technique to study cellular behavior. Our
      lab developed a lineage tracing method, based on the Cre/lox system, to
      genetically induce clonal labelling of cells and follow their progeny. Here we
      describe a protocol for temporally controlled clonal labelling and for
      microdissection of individual mouse hair follicles. We further present staining
      and visualization techniques used in our lab to analyze clones issued from
      genetically induced labelling. 

PMID- 24281871
TI  - Human keratinocyte cultures in the investigation of early steps of human
      papillomavirus infection.
AB  - Human papillomaviruses (HPVs) are non-enveloped DNA viruses that are highly
      tropic for mucosal and cutaneous epithelia. The HPV life cycle is tightly linked
      to epithelial cell differentiation, where HPVs only infect the basal
      proliferating keratinocytes, and progeny virus assembly and release only occurs
      in differentiated upper-layer keratinocytes. Therefore, human keratinocyte
      monolayer cultures provide a useful model to study the early stages of HPV
      infection. However, previous reports have shown some conflicting results of virus
      host interactions during HPV entry, which may be partly attributable to the
      different cell culture models used to examine these steps of HPV infection. Thus,
      there is a need to have a standardized in vitro model system to study virus-host
      interactions during HPV entry. Here, we describe the three most widely accepted
      keratinocyte models for studying HPV infection: primary human foreskin
      keratinocytes, normal immortalized keratinocytes, and transformed HaCaT
      keratinocytes. We also describe methods to genetically manipulate these cells,
      enabling the study of candidate host genes that may be important during HPV
      infection. Lastly, we outline simple and robust methods to assay HPV infectivity,
      which can be used to determine whether knockdown or overexpression of a
      particular gene affects HPV entry. 

PMID- 24281872
TI  - Compound screening and transcriptional profiling in human primary keratinocytes:
      a brief guideline.
AB  - Cultured human primary keratinocytes constitute suitable targets for in-depth
      evaluation of the proliferative or differentiative potential of compounds. There
      is, however, a double-edged and intrinsically inseparable transition from
      biological activity to cytotoxicity for any agent under investigation. For that
      reason, we here first of all present an established protocol for the isolation,
      cultivation, and analysis of primary foreskin-derived keratinocytes. Taking
      calcitriol as example, we then reveal how a straightforward photometric cell
      culture assay can be exploited to assess overall cell viability in response to
      increasing compound doses. With predetermined cellular cytotoxicity at hand,
      physiologically meaningful (sub-toxic) compound concentrations for subsequent
      stimulation of cells can be readily selected, and, in doing so, differentially
      expressed genes with biological significance can be reliably identified. 

PMID- 24281873
TI  - Reactive oxygen species (ROS) protection via cysteine oxidation in the epidermal
      cornified cell envelope.
AB  - The outermost layer of our skin functions as a barrier to protect us from
      physical, chemical, and biological environmental insults. This protective
      function is mediated by the epidermal cornified cell envelope (CE) which serves
      both as a mechanical and permeability barrier. Recently we have discovered that
      the CE constitutes also a first-line antioxidant shield which relies greatly on
      cysteine residues in CE precursor proteins. Here we describe methods and
      protocols to study the cysteine-mediated antioxidant function of the CE at the
      level of the whole organ (the skin), individual cells (keratinocytes), or
      isolated proteins (SPRR family).

PMID- 24281874
TI  - Cultivation of human bone-like tissue from pluripotent stem cell-derived
      osteogenic progenitors in perfusion bioreactors.
AB  - Human pluripotent stem cells represent an unlimited source of skeletal tissue
      progenitors for studies of bone biology, pathogenesis, and the development of new
      approaches for bone reconstruction and therapies. In order to construct in vitro
      models of bone tissue development and to grow functional, clinical-size bone
      substitutes for transplantation, cell cultivation in three-dimensional
      environments composed of porous osteoconductive scaffolds and dynamic culture
      systems-bioreactors-has been studied. Here, we describe a stepwise procedure for
      the induction of human embryonic and induced pluripotent stem cells (collectively
      termed PSCs) into mesenchymal-like progenitors, and their subsequent cultivation
      on decellularized bovine bone scaffolds in perfusion bioreactors, to support the
      development of viable, stable bone-like tissue in defined geometries.

PMID- 24281875
TI  - Temporalis fascia transplant for vocal fold scar and sulcus vocalis.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate vocal outcomes in 10 patients 1 year after
      autologous transplantation of temporalis fascia into Reinke's space (ATFV) for
      vocal fold scar and sulcus vocalis. STUDY DESIGN: Retrospective, clinical case
      series. METHODS: Subjective and objective evaluation was performed 12 months
      after surgery using laryngovideostroboscopy (LVS) in all patients, the Voice
      Handicap Index-10 (VHI-10) in seven patients, GRBAS (grade, roughness,
      breathiness, asthenia, strain) scale in nine patients, and noise-to-harmonics
      ratio (NHR), phonatory range (PR) and maximum phonation time (MPT) in six
      patients. RESULTS: LVS improved in all but one patient. A significant decrease
      was noted in the GRBAS subscales grade, roughness, asthenia, and strain (P<.05).
      Breathiness was almost significant, with a P value of .052. There was an average
      decrease in the VHI-10 of 8.14 (P=.032). NHR, MPT, and PR did not statistically
      improve. CONCLUSIONS: ATFV for vocal fold scar and sulcus vocalis results in
      significant subjective vocal improvement that persists at least 1 year after
      surgery. LEVEL OF EVIDENCE: 4.

PMID- 24281876
TI  - Sensing during in situ growth of Mn-doped ZnS QDs: a phosphorescent sensor for
      detection of H2S in biological samples.
AB  - Monitoring the in situ growth of Mn-doped ZnS quantum dots is shown to be a route
      to selectively detect H2S, an important endogenously produced signalling
      molecule. The use of Mn(2+) as a dopant resulted in orange phosphorescence,
      making it possible to avoid the background fluorescence from biological
      surroundings that can occur at other wavelengths. The choice of ZnS QDs as the
      host material ensured selectivity, since only sulfide can precipitate Zn(2+) and
      Mn(2+) from aqueous solution.

PMID- 24281879
TI  - Fenestranes in synthesis: unique and highly inspiring scaffolds.
AB  - The scaffold of fenestranes is quite unique, as it contains four condensed cycles
      and a distorted tetracoordinated central carbon atom with bond angles greater
      than the regular 109 degrees 28". In this Minireview, a detailed overview on the
      developments regarding this compound class, including their synthesis, is given
      for the time period since 2006. In the past years, natural products that belong
      to the class of heterofenestranes have been isolated and their syntheses will
      also be discussed. 

PMID- 24281880
TI  - Controlling mechano- and seeding-triggered single-crystal-to-single-crystal phase
      transition: molecular domino with a disconnection of aurophilic bonds.
AB  - Green and blue polymorphs: A single-crystal-to-single-crystal (SCSC) phase
      transition of phenyl(3,5-dimethylphenyl isocyanide)gold(I) was triggered by
      mechanical picking or solid seeding and propagated spontaneously with a domino
      like mechanism. As a result, one phase with intense green emission was
      transformed to another phase with weaker blue emission. 

PMID- 24281881
TI  - Reversible stabilization of transition-metal-binding DNA G-quadruplexes.
AB  - You can't top the CopperTop: Tetramolecular G-quadruplexes modified with terminal
      pyridine ligands exhibit metal-triggered stabilization as monitored by thermal
      denaturation studies, circular dichroism, and nondenaturing gel electrophoresis.
      Formation of the square-planar Cu(II) (pyridine)4 complex was confirmed by EPR
      measurements. The metal complexation is fully reversible by removal of the
      transition metal with ethylenediaminetetraacetic acid (edta). 

PMID- 24281882
TI  - Palladium and platinum eta(2) -disilyne complexes bearing an isolable
      dialkyldisilyne as a ligand.
AB  - Not so alkyne like: A dialkyldisilyne (left, green) that can be isolated is
      synthesized and fully characterized. It coordinates to palladium and platinum in
      a eta(2) -fashion giving complexes (red) with a trans-bent geometry, in contrast
      to eta(2) -alkyne complexes. The complexes showed significant metallacycle
      character. 

PMID- 24281883
TI  - Facile doping of anionic narrow-band-gap conjugated polyelectrolytes during
      dialysis.
AB  - PCPDTBTSO3 K, an anionic, narrow-band-gap conjugated polyelectrolyte, was found
      to be doped after dialysis. The proposed doping mechanism involves protonation of
      the polymer backbone, followed by electron transfer from a neutral chain, to
      generate radical cations, which are stabilized by the pendant sulfonate anions.
      Formation of polarons is supported by spectroscopy and electrical-conductivity
      measurements. 

PMID- 24281885
TI  - Efficient electron transfer in i-motif DNA with a tetraplex structure.
AB  - Electron transfer through DNA: The electron-transfer dynamics of i-motif DNA
      conjugated with pyrene (Py) and anthraquinone (AQ) has been investigated by
      fluorescence up-conversion and transient absorption spectroscopic methods.
      Electron transfer (see red arrows) in i-motif DNA is more efficient than in
      duplex DNA, suggesting that i-motif DNA can be used as electron carrier in
      nanoelectronic devices. 

PMID- 24281884
TI  - Generation of stereochemically defined tetrasubstituted enolborinates by 1,4
      hydroboration of alpha,beta-unsaturated morpholine carboxamides with
      (diisopinocampheyl)borane.
AB  - On all fours: The title reaction with (Ipc)2 BH provides tetrasubstituted
      enolborinates which undergo aldol reactions with aldehydes to form products with
      all-carbon quaternary centers with exceptional diastereo- and enantioselectivity.
      A change to the substitution pattern of the starting amide leads to either
      diastereomer of the alpha-methyl-alpha-ethyl-beta-hydroxy carboxamide (1 or 2). 

PMID- 24281886
TI  - Oxidation-state-dependent photochemistry of sulfur-bridged anthracenes.
AB  - What's up sulfur? The photochemical reactivity, including a mechanistic study of
      sulfur-bridged anthracenes is reported. The oxidation state of the bridging
      sulfur (SOn ) dictates the excited-state behavior of these molecules. 

PMID- 24281887
TI  - Palladium(II)-catalyzed cyclizative cross-coupling of ortho-alkynylanilines with
      ortho-alkynylbenzamides under aerobic conditions.
AB  - Born to couple: The Pd(OAc)2 -catalyzed reaction of o-alkynylanilines (1) with o
      alkynylbenzamides (2) affords the cyclizative cross-coupling products 3 in good
      to excellent yields. Three bonds are created in the formation of two heterocycles
      tethered by a tetrasubstituted double bond. Mechanistic studies indicate that the
      reaction is initiated by aminopalladation with subsequent oxypalladation, N
      demethylation, and reductive elimination. 

PMID- 24281888
TI  - A cerium(IV)-carbon multiple bond.
AB  - Straightforward access to a cerium(IV)-carbene complex was provided by one
      electron oxidation of an anionic "ate" cerium(III)-carbene precursor, thereby
      avoiding decomposition reactions that plague oxidations of neutral cerium(III)
      compounds. The cerium(IV)-carbene complex is the first lanthanide(IV)-element
      multiple bond and involves a twofold bonding interaction of two electron pairs
      between cerium and carbon. 

PMID- 24281889
TI  - Magnetically triggered dual functional nanoparticles for resistance-free
      apoptotic hyperthermia.
AB  - Overcoming resistance: Heat-treated cancer cells possess a protective mechanism
      for resistance and survival. Resistance-free apoptosis-inducing magnetic
      nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing
      cell survival by triggering two functional units of heat generation and the
      release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an
      alternating magnetic field (AMF). 

PMID- 24281890
TI  - Elucidating the neurotoxicity of the star fruit.
AB  - Caramboxin: Patients suffering from chronic kidney disease are frequently
      intoxicated after ingesting star fruit. The main symptoms of this intoxication
      are named in the picture. Bioguided chemical procedures resulted in the discovery
      of caramboxin, which is a phenylalanine-like molecule that is responsible for
      intoxication. Functional experiments in vivo and in vitro point towards the
      glutamatergic ionotropic molecular actions of caramboxin, which explains its
      convulsant and neurodegenerative properties. 

PMID- 24281891
TI  - Improving outcomes in emergency surgery.

PMID- 24281892
TI  - Highly efficient C-H hydroxylation of carbonyl compounds with oxygen under mild
      conditions.
AB  - A transition-metal-free Cs2 CO3 -catalyzed alpha-hydroxylation of carbonyl
      compounds with O2 as the oxygen source is described. This reaction provides an
      efficient approach to tertiary alpha-hydroxycarbonyl compounds, which are highly
      valued chemicals and widely used in the chemical and pharmaceutical industry. The
      simple conditions and the use of molecular oxygen as both the oxidant and the
      oxygen source make this protocol very environmentally friendly and practical.
      This transformation is highly efficient and highly selective for tertiary C(sp(3)
      )?H bond cleavage. 

PMID- 24281893
TI  - Influence of caffeine and sodium citrate ingestion on 1,500-m exercise
      performance in elite wheelchair athletes: a pilot study.
AB  - The aim of this study was to investigate whether caffeine and/or sodium citrate
      have an ergogenic effect on the 1,500-m exercise performance in elite wheelchair
      athletes. A placebo-controlled, randomized, cross-over and double-blind study
      design was conducted with the four treatments placebo, caffeine, sodium citrate
      and the combination of caffeine and sodium citrate. Nine healthy, elite
      wheelchair-racing athletes (median: [min; max] age: 28 y [23; 54]; height: 173 cm
      [165; 188]; weight: 62.9 kg [48.9; 68.4], category T53/54) completed the study.
      All athletes were national team members, including several Paralympic Games,
      World and European Championship medalists. The athletes performed a 1,500-m time
      trial four times on a wheelchair training roller. Time to complete 1,500-m, pH,
      bicarbonate and sodium concentration as well as lactate concentration were
      measured. The time to complete 1,500-m was not significantly different between
      the four treatments (placebo: 170.6 s [141.7; 232.0]; caffeine: 179.5 s [134.8;
      239.6]; sodium citrate: 178.3 s [136.4; 247.1]; combination: 177.6 s [136.1;
      256.2]). However, pH and bicarbonate concentrations were significantly increased
      with sodium citrate ingestion compared with placebo. Moreover, maximal lactate
      concentrations were significantly higher in the caffeine and the combination
      treatment compared with placebo. The supplementation with sodium citrate and/or
      caffeine did not provide an ergogenic effect on the 1,500-m exercise performance
      in wheelchair elite athletes.

PMID- 24281894
TI  - FVIII/VWF ratio is not a reliable predictor of VWD in children.
AB  - Adults with von Willebrand Disease (VWD) are known to have a ratio of factor VIII
      activity (FVIII:C) to von Willebrand factor antigen (VWF:Ag) greater than 1. We,
      however, noted healthy children with ratios that are unexpectedly high. Though
      the FVIII:C/VWF:Ag ratio differs significantly between healthy children and VWD
      patients in some age groups, the substantial overlap of observed ranges suggests
      that a ratio threshold-based screening approach alone cannot reliably
      discriminate between these groups. The diagnostic performance of this ratio is
      poor for VWD in children, which may decrease its value as a screening tool in the
      pediatric population.

PMID- 24281895
TI  - Bonding effectiveness to different chemically pre-treated dental zirconia.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of different
      chemical pre-treatments on the bond durability to dental zirconia. METHODS: Fully
      sintered IPS e.max ZirCAD (Ivoclar Vivadent) blocks were subjected to
      tribochemical silica sandblasting (CoJet, 3M ESPE). The zirconia samples were
      additionally pre-treated using one of four zirconia primers/adhesives (Clearfil
      Ceramic Primer, Kuraray Noritake; Monobond Plus, Ivoclar Vivadent; Scotchbond
      Universal, 3M ESPE; Z-PRIME Plus, Bisco). Finally, two identically pre-treated
      zirconia blocks were bonded together using composite cement (RelyX Ultimate, 3M
      ESPE). The specimens were trimmed at the interface to a cylindrical hourglass and
      stored in distilled water (7 days, 37  degrees C), after which they were randomly
      tested as is or subjected to mechanical ageing involving cyclic tensile stress
      (10 N, 10 Hz, 10,000 cycles). Subsequently, the micro-tensile bond strength was
      determined, and SEM fractographic analysis performed. RESULTS: Weibull analysis
      revealed the highest Weibull scale and shape parameters for the 'Clearfil Ceramic
      Primer/mechanical ageing' combination. Chemical pre-treatment of CoJet (3M ESPE)
      sandblasted zirconia using Clearfil Ceramic Primer (Kuraray Noritake) and
      Monobond Plus (Ivoclar Vivadent) revealed a significantly higher bond strength
      than when Scotchbond Universal (3M ESPE) and Z-PRIME Plus (Bisco) were used.
      After ageing, Clearfil Ceramic Primer (Kuraray Noritake) revealed the most stable
      bond durability. CONCLUSION: Combined mechanical/chemical pre-treatment, the
      latter with either Clearfil Ceramic Primer (Kuraray Noritake) or Monobond Plus
      (Ivoclar Vivadent), resulted in the most durable bond to zirconia. CLINICAL
      RELEVANCE: As a standard procedure to durably bond zirconia to tooth tissue, the
      application of a combined 10-methacryloyloxydecyl dihydrogen phosphate/silane
      ceramic primer to zirconia is clinically highly recommended.

PMID- 24281898
TI  - Two sides of the one coin-the cardiac and vascular system.

PMID- 24281896
TI  - Monounsaturated 14:1n-9 and 16:1n-9 fatty acids but not 18:1n-9 induce apoptosis
      and necrosis in murine HL-1 cardiomyocytes.
AB  - Patients with inborn errors of long-chain fatty acid oxidation accumulate disease
      specific acylcarnitines and triacylglycerols in various tissues. Some of these
      patients present significant cardiac diseases such as arrhythmias and
      cardiomyopathy. The mechanism of how fatty acid accumulation is involved in
      disease pathogenesis is still unclear but apoptosis of cardiomyocytes has been
      suggested to be one possible mechanism of cardiomyopathy development. In this
      study, we measured lipid uptake and intracellular lipid accumulation after
      incubation of HL1 cardiomyocytes with different saturated and monounsaturated
      long- and medium-chain fatty acid species for various time periods and at
      different physiological concentrations. We assessed apoptosis induction by
      analyzing the mitochondrial membrane potential and TLR-4 expression as well as
      the composition of the accumulating triacylglycerols. We identified only 14:1 and
      16:1 monounsaturated fatty acids potentially leading to an increase in TLR-4
      expression and disruption of the mitochondrial membrane potential, resulting in
      apoptosis and necrosis in cultured cardiomyocytes. This study demonstrates
      significant toxicity of especially those fatty acid species in vitro that
      significantly accumulate in fatty acid oxidation defects presenting with cardiac
      disease such as very long-chain acyl-CoA dehydrogenase, carnitine acylcarnitine
      translocase and carnitine palmitoyl-CoA transferase deficiencies. 

PMID- 24281899
TI  - Severe granulomatous reaction associated with hypercalcemia occurring after
      silicone soft tissue augmentation of the buttocks: a case report.
AB  - Liquid silicone is a permanent filler. Its use to augment soft tissues for
      aesthetic purposes was widespread worldwide in the 1960s. Although initially
      considered to be biologically inert, this substance may cause, after its
      injection, an inflammatory granulomatous effect of variable severity and, in very
      rare cases, a severe hypercalcemia, which can be life threatening. The reported
      case highlights the well-known physiopathology of hypercalcemia, and the various
      therapeutic options are discussed. LEVEL OF EVIDENCE V: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 24281900
TI  - Midface contour change after reduction malarplasty with a modified L-shaped
      osteotomy: a surgical outcomes study.
AB  - BACKGROUND: The zygomatic bone, which is located on both sides of the midface,
      significantly contributes to the overall facial form. Asian people usually have a
      wide midface and prominent zygoma. Reduction malarplasty is one of the most
      frequently performed facial contouring surgeries in Asian countries. This study
      aimed to evaluate the surgical outcomes of reduction malarplasty with a modified
      L-shaped osteotomy. METHODS: This study evaluated surgical outcomes of 30
      patients (3 men and 27 women) who had undergone reduction malarplasty with a
      modified L-shaped osteotomy. Photogrammetric analysis using graphics software was
      performed, and the prominence and height of the malar eminence were measured in
      the presurgical and postsurgical photographs. Attractiveness quotients were rated
      based on visual assessment of the presurgical and postsurgical groups. RESULTS:
      The malar eminence showed a significant decrease in prominence between the
      presurgical and postsurgical groups (P < 0.001) without a significant change in
      height. Facial attractiveness increased significantly after surgery. CONCLUSIONS:
      We devised a simple and intuitive method for the photographic measurement of the
      malar prominence. Reduction malarplasty with a modified L-shaped osteotomy
      resulted in a notably reduced malar prominence without obvious downward
      displacement of the malar eminence. LEVEL OF EVIDENCE V: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266.

PMID- 24281901
TI  - Commentary on "The labial aging process: a surface analysis-based three
      dimensional evaluation".

PMID- 24281902
TI  - A fraction containing kaempferol-3,4'-dimethylether from Larrea divaricata Cav.
      induces macrophage activation on mice infected with Candida albicans.
AB  - Larrea divaricata Cav. is a plant growing in South America. Both the infusion and
      a derived fraction (F1) of L. divaricata have proved to have immunomodulatory
      properties. Moreover, F1 can activate macrophages obtained from mice infected
      with Candida albicans. In this work, F1 was administrated to infected animals,
      and the state and type of activation of resident macrophages were studied.
      Results showed that F1 was able to activate macrophages obtained from infected
      mice by both classical and alternative pathways, probably by inducing a
      translocation of nuclear factor kappa-B. F1 increases not only the lysosomal
      activity of macrophages but also the production of phagosomal superoxide anion as
      a consequence of the activation of the Nicotinamide adenine dinucleotide
      phosphate oxidase (NADPH oxidase) complex. F1 induced an increase in the
      macrophage capacity to kill the fungus, which was reflected in a decrease in the
      levels of colonization of organs. A main flavonoid, kaempferol-3,4'
      dimethylether, was identified in F1 by HPLC. This compound increased in vitro
      production of nitric oxide in heat-killed C. albicans-stimulated macrophages. The
      flavonoid could thus be considered one of the responsible molecules mediating the
      overall effects of F1 on the immune system in infected animals.

PMID- 24281903
TI  - Lipoprotein apheresis reduces biomarkers of plaque destabilization and
      cardiovascular risk.
AB  - Lipoprotein apheresis (LA) is believed to exert anti-atherosclerotic effects
      beyond LDL-cholesterol reduction. We investigated 22 patients undergoing regular
      LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15
      healthy individuals (group B), and 22 hyperlipoproteinemic patients with
      concomitant cardiovascular end organ damage treated without LA therapy (group C).
      Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and
      rupture (sVCAM, MMP-9, PAPP-A, ADMA) were quantified. Intergroup comparison
      revealed a statistically significant lower MMP-9 level in group A (AP and EP)
      compared with group C (P < 0.01), whereas PAPP-A levels were lower in group B
      compared with group A and C (P = 0.04). EP ADMA-levels and EP sVCAM levels in
      group A were statistically lower compared with group B and C. AP and EP values
      comparison revealed a significant reduction for hsCRP (mean 41.0 +/- 16.7%, P <
      0.01), sVCAM (mean 69.6 +/- 14.0%, P < 0.01), PAPP-A (mean 88.7 +/- 20.4%, P <
      0.01), ADMA (mean 69.7 +/- 18.4% P < 0.01). In conclusion, we observed a
      transient decrease in the plasma concentrations of several biomarkers expressed
      during plaque destabilization and elevated cardiovascular risk after a single LA
      treatment.

PMID- 24281904
TI  - Prognostic value of myocardium perfusion imaging with a new reconstruction
      algorithm.
AB  - BACKGROUND: It has been demonstrated that a new reconstruction algorithm for
      myocardium perfusion imaging (MPI) allows faster acquisition with similar
      accuracy. The prognostic value of MPI performed with this software and short
      acquisition time is unknown. METHODS: To determine the prognostic value we
      followed 3184 consecutive MPI patients between March 2008 and March 2010. A 2-day
      protocol with low dose 99mTc-MIBI (10-12 mCi) and a 6-minute acquisition was
      used. Exercise stress was used in 62.6% of the studies. Scans were reconstructed
      using the software "Evolution for cardiac". Perfusion defects were quantified by
      summed stress score (SSS) and categorized in four groups: SSS0 = 0; SSS1 = 1-3;
      SSS2 = 4-8; and SSS3 >= 9. Patients were phone contacted every 6 months for
      follow up and hard events were defined as death or myocardial infarction (MI) and
      total events as hard events plus late revascularization. RESULTS: The mean
      radiation dose was <7 mSv/patient. Mean F/U was 33 +/- 20 months; 140 of the
      patients were lost to follow up and 86 were censored due early revascularization
      (<60 days after MPS). There were 140 hard events: 89 deaths and 51 MI. Mean age
      was 61.5 +/- 12.3 years and 57.7% were male. Hard event rate was 0.8%/year in
      patients with normal MPS and 3.7%/year in those with abnormal MPS. Patients with
      larger defects had nine times more hard events than patients with SSS = 0 (14.2%
      vs 1.6%). Revascularization was more frequent in patients with abnormal MPS than
      normal MPS (21.7% vs 3.9%; P < 0.001). Cox proportional hazard analysis showed
      that SSS was an independent predictor of hard events and revascularization.
      CONCLUSIONS: The use of reduced-dose, fast myocardial perfusion SPECT and the new
      processing algorithm lowers acquisition time and radiation exposure compared to
      conventional SPECT without compromising the well-established prognostic value of
      MPI.

PMID- 24281905
TI  - Randomized clinical trial of perioperative omega-3 fatty acid supplements in
      elective colorectal cancer surgery.
AB  - BACKGROUND: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects,
      and n-3 FA supplements may improve outcome after surgery. METHODS: In a
      randomized double-blind placebo-controlled trial in single centre, patients
      referred for elective colorectal cancer surgery received either an n-3 FA
      enriched oral nutritional supplement (ONS) (Supportan, 200 ml twice daily)
      providing 2.0 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)
      per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7
      days after surgery. The primary endpoint was infectious and non-infectious
      complications within 30 days of surgery. Secondary endpoints were length of
      hospital stay, intensive care unit admission, readmissions, and concentrations of
      marine n-3 FAs and arachidonic acid in granulocyte membranes. RESULTS: Some 148
      consecutive patients (68 women, 80 men; mean age 71 (range 41-89) years) were
      randomized. There was no significant difference between groups in infectious or
      non-infectious postoperative complications (P = 1.000). Granulocyte levels of
      EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA
      enriched supplement group compared with the control group (P < 0.001). The
      arachidonic acid level in granulocytes was significantly lower in the enriched
      group than in the control group (P < 0.001). CONCLUSION: EPA, DHA and DPA were
      incorporated into granulocytes in patients receiving n-3 FAs, but this was not
      associated with improved postoperative outcomes. REGISTRATION NUMBER: NCT00488904
      (http://www.clinicaltrials.gov).

PMID- 24281906
TI  - Effect of aging on hypopharyngeal safe volume and the aerodigestive reflexes
      protecting the airways.
AB  - OBJECTIVES/HYPOTHESIS: Studies on young volunteers have shown that aerodigestive
      reflexes are triggered before the maximum volume of fluid that can safely collect
      in the hypopharynx before spilling into the larynx is exceeded (hypopharyngeal
      safe volume [HPSV]). The objective of this study was to determine the influence
      of aging on HPSV and pharyngo-glottal closure reflex (PGCR), pharyngo-UES
      contractile reflex (PUCR), and reflexive pharyngeal swallow (RPS). STUDY DESIGN:
      Comparison between two groups of different age ranges. METHODS: Ten young (25 +/-
      3 standard deviation [SD] years) and 10 elderly (77 +/- 3 SD years) subjects were
      studied. PGCR, PUCR, and RPS were elicited by perfusing water into the pharynx
      rapidly and slowly. HPSV was determined by abolishing RPS with pharyngeal
      anesthesia. RESULTS: Frequency-elicitation of PGCR and PUCR were significantly
      lower in the elderly compared to the young during slow water perfusion (47% vs.
      97% and 40% vs. 90%, respectively, P < .001). RPS was absent in five of the 30
      (17%) slow injections in the elderly group. In these elderly subjects, HPSV was
      exceeded and laryngeal penetration of the water was seen. The threshold volume to
      elicit PGCR, PUCR, and RPS was significantly lower than the HPSV during rapid
      injections. Except for RPS, these volumes were also significantly lower than HPSV
      during slow injections. CONCLUSIONS: PGCR, PUCR, and RPS reflexes are triggered
      at a threshold volume significantly lower than the HPSV in both young and elderly
      subjects. Lower frequency-elicitation of PGCR, PUCR, and RPS in the elderly can
      predispose them to the risks of aspiration.

PMID- 24281908
TI  - Visible-light sensitization of vinyl azides by transition-metal photocatalysis.
AB  - Irradiation of vinyl and aryl azides with visible light in the presence of Ru
      photocatalysts results in the formation of reactive nitrenes, which can undergo a
      variety of C-N bond-forming reactions. The ability to use low-energy visible
      light instead of UV in the photochemical activation of azides avoids competitive
      photodecomposition processes that have long been a significant limitation on the
      synthetic use of these reactions.

PMID- 24281909
TI  - Frequency and antimicrobial resistance of diarrhoeagenic Escherichia coli from
      young children in Iran.
AB  - Diarrhoea continues to be one of the most common causes of morbidity and
      mortality among infants and children in developing countries. Diarrhoeagenic
      Escherichia coli (DEC) is an emerging agent among pathogens that cause diarrhoea.
      Between March 2011 and January 2012, a total of 600 stool specimens from children
      younger than 5 years of age (450 with and 150 without diarrhoea) were
      investigated for enteroaggregative E. coli (EAEC), enterohaemorrhagic E. coli
      (EHEC), enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) using
      PCR. Antimicrobial susceptibility testing was performed following Clinical and
      Laboratory Standards Institute guidelines. The prevalence of DEC pathotypes was
      30.4% (137 patients) and 12% (18 patients) in the diarrhoea group and the control
      group, respectively. The most frequently isolated pathotype in diarrhoeal
      children was ETEC. This pathotype was detected significantly more often in
      children with diarrhoea (14.4%) than in children without diarrhoea (5.3%). EAEC
      and EPEC were detected with slightly higher frequencies in children with (8 and
      4.2%, respectively) than in children without (4.6 and 2%, respectively) (P>0.05)
      diarrhoea. EHEC was only detected in children with diarrhoea (3.8%). Of the
      children from the diarrhoea group, 10% were colonized with more than one DEC
      pathotype. The DEC isolates exhibited high-level resistance to erythromycin
      (100%), azteronam (80.7%), amoxicillin (74.4%) and tetracycline (69.3%), and
      86.4% of isolates were multidrug resistant. In conclusion, ETEC continues to be
      an important agent associated with diarrhoea in children from Tabriz, Iran.

PMID- 24281910
TI  - Plasmon-mediated syntheses of metallic nanostructures.
AB  - The ability to prepare noble metal nanostructures of a desired composition, size,
      and shape enables their resulting properties to be exquisitely tailored, which
      has led to the use of these structures in numerous applications, ranging from
      medicine to electronics. The prospect of using light to guide nanoparticle
      reactions is extremely attractive since one can, in principle, regulate particle
      growth based on the ability of the nanostructures to absorb a specific excitation
      wavelength. Therefore, using the nature of light, one can generate a homogenous
      population of product nanoparticles from a heterogeneous starting population. The
      best example of this is afforded by plasmon-mediated syntheses of metal
      nanoparticles, which use visible light irradiation and plasmon excitation to
      drive the chemical reduction of Ag(+) by citrate. Since the initial discovery
      that Ag triangular prisms could be prepared by the photo-induced conversion of Ag
      spherical nanoparticles, plasmon-mediated synthesis has become a highly
      controllable technique for preparing a number of different Ag particles with
      tight control over shape, as well as a wide variety of Au-Ag bimetallic
      nanostructures. We discuss the underlying physical and chemical factors that
      drive structural selection and conclude by outlining some of the important design
      considerations for controlling particle shape as learned through studies of
      plasmon-mediated reactions, but applicable to all methods of noble metal
      nanocrystal synthesis. 

PMID- 24281907
TI  - A systems neuroscience approach to the pathophysiology of pediatric mood and
      anxiety disorders.
AB  - Emotional dysregulation is a core feature of pediatric mood and anxiety
      disorders. Emerging evidence suggests that these disorders are mediated by
      abnormalities in the functions and structures of the developing brain. This
      chapter reviews recent behavioral and functional magnetic resonance imaging
      (fMRI) research on pediatric mood and anxiety disorders, focusing on the neural
      mechanisms underlying these disorders. Throughout the chapter, we highlight the
      relationship between neural and behavioral findings, and potential novel
      treatments. The chapter concludes with directions for future research. 

PMID- 24281911
TI  - Preexercise carbohydrate feeding and high-intensity exercise capacity: effects of
      timing of intake and carbohydrate concentration.
AB  - The present study aimed to investigate the influence of timing of preexercise
      carbohydrate feeding (Part A) and carbohydrate concentration (Part B) on short
      duration high-intensity exercise capacity. In Part A, 17 males, and in Part B 10
      males, performed a peak power output (PPO) test, two familiarization trials at
      90% of PPO, and 4 (for Part A) or 3 (for Part B) experimental trials involving
      exercise capacity tests at 90% PPO. In Part A, the 4 trials were conducted
      following ingestion of a 6.4% carbohydrate/electrolyte sports drink ingested 30
      (C30) or 120 (C120) minutes before exercise, or a flavor-matched placebo
      administered either 30 (P30) or 120 (P120) minutes before exercise. In Part B,
      the 3 trials were performed 30 min after ingestion of 0%, 2% or 12% carbohydrate
      solutions. All trials were performed in a double-blind cross-over design
      following and overnight fast. Dietary intake and activity in the 2 days before
      trials was recorded and replicated on each visit. Glucose, lactate, heart rate,
      and mood/arousal were recorded at intervals during the trials. In Part A, C30
      produced the greatest exercise capacity (mean +/- SD; 9.0 +/- 1.9 min, p < .01)
      compared with all other trials (7.7 +/- 1.5 min P30, 8.0 +/- 1.7 min P120, 7.9 +/
      1.9 min C120). In Part B, exercise capacity (min) following ingestion of the 2%
      solution (9.2 +/- 2.1) compared with 0% (8.2 +/- 0.7) and 12% (8.0 +/- 1.3)
      solutions approached significance (p = .09). This study provides new evidence to
      suggest that timing of carbohydrate intake is important in short duration high
      intensity exercise tasks, but a concentration effect requires further
      exploration. 

PMID- 24281912
TI  - Re: Evaluation of renal function after successful treatment for unilateral non
      syndromic Wilms tumor.

PMID- 24281914
TI  - Unique picoeukaryotic algal community under multiple environmental stress
      conditions in a shallow, alkaline pan.
AB  - Winter phytoplankton communities in the shallow alkaline pans of Hungary are
      frequently dominated by picoeukaryotes, sometimes in particularly high abundance.
      In winter 2012, the ice-covered alkaline Zab-szek pan was found to be
      extraordinarily rich in picoeukaryotic green algae (42-82 * 10(6) cells ml(-1))
      despite the simultaneous presence of multiple stressors (low temperature and
      light intensity with high pH and salinity). The maximum photosynthetic rate of
      the picoeukaryote community was 1.4 MUg C MUg chlorophyll a (-1) h(-1) at 125
      MUmol m(-2) s(-1). The assimilation rates compared with the available light
      intensity measured on the field show that the community was considerably light
      limited. Estimated areal primary production was 180 mg C m(-2) d(-1). On the
      basis of the 18S rRNA gene analysis (cloning and DGGE), the community was
      phylogenetically heterogeneous with several previously undescribed chlorophyte
      lineages, which indicates the ability of picoeukaryotic communities to maintain
      high genetic diversity under extreme conditions.

PMID- 24281913
TI  - FDG PET/CT is useful for detecting infiltration to the port site in patients with
      malignant pleural mesothelioma.
AB  - OBJECTIVE: One reason for the poor outcomes of multimodality therapies, including
      macroscopic complete resection, in patients with malignant pleural mesothelioma
      (MPM) is the difficulty of correctly staging the disease, which can result in
      incomplete resection. The purpose of this study was to investigate the aspects of
      tumor infiltration to the port site and the usefulness of preoperative FDG PET/CT
      for diagnosing MPM. METHODS: Between June 2007 and May 2013, 21 patients who
      underwent surgical treatment with curative intent for MPM that had been
      previously diagnosed on a video-assisted thoracic surgery (VATS) biopsy were
      included in this study. RESULTS: There were 17 males and four females, with a
      mean age of 63 years. The accumulation of FDG at the port site was observed in
      all nine patients with tumor infiltration to the port site, whereas this feature
      was not noted in 15 patients without tumor extension to the port site. There were
      more positive lymph node cases in the infiltration group than in the non
      infiltration group (p = 0.02). No significant differences in survival were
      observed between the patients with and without tumor infiltration to the port
      site. CONCLUSIONS: FDG PET/CT is useful for detecting tumor infiltration of MPM
      to the port site and may help to prevent local recurrence, especially port site
      relapse, following macroscopic complete resection. However, this condition is
      related to tumor aggressiveness; therefore, performing careful staging and
      determining the appropriate treatment strategy are required in such patients.

PMID- 24281915
TI  - beta-Sitosterol enhances cellular glutathione redox cycling by reactive oxygen
      species generated from mitochondrial respiration: protection against oxidant
      injury in H9c2 cells and rat hearts.
AB  - Herba Cistanches (Cistanche deserticola Y. C. Ma) is a 'Yang-invigorating' tonic
      herb in Chinese medicine. Preliminary chemical analysis indicated that beta
      sitosterol (BS) is one of the chemical constituents in an active fraction of
      Herba Cistanches. To investigate whether BS is an active ingredient of Herba
      Cistanches, the effects of BS on H9c2 cells and rat hearts were examined. The
      results indicated that BS stimulated the mitochondrial ATP generation capacity in
      H9c2 cells, which was associated with the increased production of mitochondrial
      reactive oxygen species. BS also stimulated mitochondrial state 3 and state 4
      respiration, with the resultant decrease in coupling efficiency. BS produced an
      up-regulation of cellular glutathione redox cycling and protected against
      hypoxia/reoxygenation-induced apoptosis in H9c2 cells. However, the protective
      effect of BS against myocardial ischemia/reperfusion injury was seen in female
      but not male rats ex vivo. The cardioprotection afforded by BS was likely
      mediated by an up-regulation of mitochondrial glutathione redox cycling in female
      rat hearts. In conclusion, the ensemble of results suggests that BS is an active
      ingredient of Herba Cistanches. The gender-dependent effect of BS on myocardial
      protection will further be investigated.

PMID- 24281916
TI  - How can we improve tracking of transplanted tissue in the United States?
AB  - Currently an estimated two million tissues are distributed for transplantation
      annually. With increasing use of recovered tissue, clusters of transplant
      transmitted infection have shown the difficulty of tracking tissues from an
      infected donor to the recipient. The challenge of tissue tracking to multiple
      transplant recipients was illustrated in a recent investigation of transmission
      of hepatitis C virus infection from a donor of organs and tissues. When a tissue
      bank issued a recall of the donated tissue, the Centers for Disease Control and
      Prevention was notified to assist public health authorities; the mean time to
      locate and notify the physicians who had transplanted the tissue was 13 days,
      while the mean time to notify, inform, and test the patients was 29 days. Lack of
      common coding and nomenclature was one of the key challenges in tracking tissue
      to the recipient. Some changes that could improve timeliness in the event of a
      recall includes: (1) standardized tissue nomenclature and coding through unique
      donor identifiers; (2) tissue traceability requirements using systems similar to
      that used for blood products; (3) a surveillance system for adverse events that
      provides feedback at the provider level.

PMID- 24281917
TI  - Carrots and sticks: New Brunswick and Maine forest landowner perceptions toward
      incentives and regulations.
AB  - The governments of countries that allow private land ownership have two main
      tools to motivate landowner behavior: regulations and incentives. This research
      examines landowner preferences toward these policy tools and asks specifically:
      Do private forest landowners in New Brunswick and Maine believe that regulations
      and/or incentives are effective means to motivate responsible stewardship? Can
      landowners identify explicit regulations and policies that restrict property
      rights? Also, we were interested to see if any discernible differences existed
      between these adjacent jurisdictions from different countries, but that share
      similar forests and a similar settlement history. We identified and interviewed
      diverse landowners, recorded and transcribed our discussions, and analyzed the
      results using a grounded theory approach. Findings suggest that both New
      Brunswick and Maine participants are fairly comfortable with most regulations and
      many agreed that a combination of incentives and regulations are in fact useful.
      Furthermore, landowners in New Brunswick discussed non-monetary incentives as a
      mechanism to reward "good" stewardship; while Maine respondents articulated a
      degree of responsible stewardship that transcends a need to incentivize
      landowners. This study demonstrates that diverse landowners may be more
      comfortable with environmental regulations than previously understood and may be
      interested in non-monetary incentives. 

PMID- 24281918
TI  - Can't see the forest for the rice: factors influencing spatial variations in the
      density of trees in paddy fields in northeast Thailand.
AB  - The widespread presence of trees in paddy fields is a unique feature of Northeast
      Thailand's agricultural landscape. A survey of spatial variability in the density
      of trees in paddy fields in the Northeast Region was conducted utilizing high
      resolution satellite images and found that the mean density in the whole region
      was 12.1 trees/ha (varying from a high of 44.6 trees/ha to a low of 0.8
      trees/ha). In general, tree densities are higher in the southeastern part of the
      region and much lower in the northern central part. Tree density was influenced
      by multiple factors including: (1) the history of land development, with more
      recently developed paddy fields having higher densities, (2) topography, with
      fields located at higher topographical positions having a higher mean density of
      trees, (3) access to natural forest resources, with fields in areas located close
      to natural forests having higher densities, (4) amount of annual rainfall, with
      fields in areas with higher average annual rainfall having higher tree densities,
      and (5) landholding size, with fields in areas with larger-sized landholdings
      having more trees. However, there is a considerable extent of co-variation among
      these factors. Although trees remain an important element of the paddy field
      landscape in the Northeast, it appears that their density has been declining in
      recent years. If this trend continues, then the vast "invisible forest"
      represented by trees in paddy fields may truly disappear, with negative
      consequences for the villagers' livelihoods, biodiversity conservation, and
      carbon sequestration in the rural ecosystem.

PMID- 24281919
TI  - Effects of facility developments and encounter levels on perceptions of settings,
      crowding, and norms in a korean park.
AB  - This article examines potential effects of two physical developments (presence or
      absence of an aerial tramway, a road vs. a trail) and one social variable
      (increasing encounters with other people) on individuals' perceptions of settings
      (i.e., perceived settings), crowding, and acceptance of encounters (i.e., norms)
      in Mudeungsan Provincial Park in South Korea, where there have been proposals for
      a new aerial tramway. Data were obtained from 241 students at Chonnam National
      University, almost all of whom had previously visited this park (e.g., 66 %
      visited at least one of the two study locations in this park, 55 % visited this
      park in the past 12 months). Simulated photographs showed encounter levels (1 or
      15 hikers), the presence or absence of a tramway, and a road versus a trail.
      Respondents encountering low numbers of other people felt less crowded,
      considered these use levels to be more acceptable, and perceived the area as more
      pristine and less developed. Locations containing an aerial tramway were
      perceived as more developed and less natural, and higher encounter levels were
      considered to be more acceptable at these locations. Whether settings contained a
      road or a trail did not influence perceived settings, crowding, or norms.
      Implications of these findings for future research and management of parks and
      related outdoor settings are discussed.

PMID- 24281920
TI  - Resource selection probability functions for gopher tortoise: providing a
      management tool applicable across the species' range.
AB  - The gopher tortoise (Gopherus polyphemus) is protected by conservation policy
      throughout its range. Efforts to protect the species from further decline demand
      detailed understanding of its habitat requirements, which have not yet been
      rigorously defined. Current methods of identifying gopher tortoise habitat
      typically rely on coarse soil and vegetation classifications, and are prone to
      over-prediction of suitable habitat. We used a logistic resource selection
      probability function in an information-theoretic framework to understand the
      relative importance of various environmental factors to gopher tortoise habitat
      selection, drawing on nationwide environmental datasets, and an existing tortoise
      survey of the Ft. Benning military base. We applied the normalized difference
      vegetation index (NDVI) as an index of vegetation density, and found that NDVI
      was strongly negatively associated with active burrow locations. Our results
      showed that the most parsimonious model included variables from all candidate
      model types (landscape features, topography, soil, vegetation), and the model
      groups describing soil or vegetation alone performed poorly. These results
      demonstrate with a rigorous quantitative approach that although soil and
      vegetation are important to the gopher tortoise, they are not sufficient to
      describe suitable habitat. More widely, our results highlight the feasibility of
      constructing highly accurate habitat suitability models from data that are widely
      available throughout the species' range. Our study shows that the widespread
      availability of national environmental datasets describing important components
      of gopher tortoise habitat, combined with existing tortoise surveys on public
      lands, can be leveraged to inform knowledge of habitat suitability and target
      recovery efforts range-wide. 

PMID- 24281921
TI  - Revisits and postoperative hemorrhage after adult tonsillectomy.
AB  - OBJECTIVES/HYPOTHESIS: Determine revisits and reasons for revisits after adult
      tonsillectomy. STUDY DESIGN: Cross-sectional analysis of multistate ambulatory
      surgery and hospital databases. METHODS: Ambulatory adult tonsillectomies
      performed as the sole procedure were extracted from the State Ambulatory Surgery
      databases for New York, Florida, Iowa, and California for 2010. Cases were linked
      to the State Emergency Department databases and the State Inpatient databases for
      visit encounters occurring 0 to 14 days after tonsillectomy. The number of
      revisits (including readmissions) was determined as well as the reason for
      revisit categorized as post-tonsillectomy bleeding, acute pain, or
      fever/dehydration. The overall rate of occurrence of and intervention rate for
      post-tonsillectomy bleeding was determined. RESULTS: A total of 7,748 adult
      tonsillectomies were examined (mean age, 29.2 years; 64.4% female). Overall,
      11.6% of patients had a revisit after tonsillectomy (9.6% revisited the
      ambulatory surgery center, 78.8% the emergency department, and 11.6% to inpatient
      admission). The primary diagnoses at the first revisit were bleeding (41.3%),
      acute pain (22.1%), and fever/dehydration (13.2%). Overall, 2.1% of patients
      incurred a second revisit after adult tonsillectomy (10.7% of these to inpatient
      admission). Among all tonsillectomies, 4.8% of adult tonsillectomies presented
      with a bleeding diagnosis at a first revisit. Overall, 2.2% underwent a procedure
      to control bleeding at a first revisit. CONCLUSIONS: The current data quantify at
      a multistate level revisits, revisit diagnoses, and procedural rates for post
      tonsillectomy bleeding in the adult population. Interventions to offset revisits
      for acute pain and fever/dehydration should be explored to decrease adult
      tonsillectomy morbidity. LEVEL OF EVIDENCE: 2b.

PMID- 24281922
TI  - A nomogram to calculate the Physiological and Operative Severity Score for the
      enUmeration of Mortality and morbidity (POSSUM).
AB  - BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of
      Mortality and morbidity (POSSUM) is a well validated model for the prediction of
      perioperative mortality and morbidity with application to surgery and intensive
      care medicine. The outcome measure calculations are time-consuming, complex and
      potentially error-prone. Nomograms are low-cost easy-to-use graphic devices that
      can be used to make repeated calculations to an acceptable level of accuracy for
      most clinical purposes. This paper describes a nomogram to aid calculation of
      POSSUM scores. METHODS: This graphic solution consists of two sections: a tally
      sheet to calculate physiological and operative severity scores (PS and OS), and a
      nomogram to calculate mortality and morbidity. The latter was designed using
      standard mathematical methods, and drafted with the aid of commercially available
      software. Accuracy was confirmed by using a spreadsheet to generate 120 random
      sets of simulated values for PS and OS, and corresponding calculated values for
      predicted mortality and morbidity. The outcome values in each case were derived
      using the nomogram and compared with the spreadsheet values using Bland-Altman
      analysis. RESULTS: Bland-Altman analysis showed close agreement between nomogram
      and spreadsheet. Bias of the nomogram was -0.1 percentage points for mortality
      and 0.1 percentage points for morbidity, with limits of agreement of -2.1 to +1.9
      and -1.4 to +1.6 percentage points for mortality and morbidity respectively.
      Correlation coefficients were r > 0.999 and P < 0.001 for both mortality and
      morbidity. CONCLUSION: The nomogram provides a rapid, accurate, low-cost means of
      performing, visualizing and cross-checking POSSUM calculations.

PMID- 24281923
TI  - Iridium-catalyzed asymmetric ring-opening reactions of azabenzonorbornadiene with
      carboxylic acid nucleophiles.
AB  - Iridium-catalyzed asymmetric ring-opening reaction of N-substituted
      azabenzonorbornadienes with various carboxylic acids has been developed. The ring
      opening reaction offered trans-1,2-dihydronaphthalene products containing an
      allylic carboxylate moiety in moderate yields (up to 89 %) with high
      enantioselectivities (up to 96 %). The trans-configuration of the products was
      confirmed by X-ray crystallography.

PMID- 24281925
TI  - [Vesicoureteral Reflux - Ambulatory Blood Pressure Monitoring useful for patients
      with renal scarring].

PMID- 24281924
TI  - Ionic liquid-supported synthesis of piperazine derivatives as potential
      insecticides.
AB  - With the purpose of extending our efforts on the search and synthesis of new
      insecticides with novel acting modes, a series of novel 4-(2-(4-(pyridin-2
      yl)piperazin-1-yl)ethoxy)aniline derivatives were designed based on classical
      serotonin receptor ligands and synthesized through the rapid ionic liquid
      supported parallel synthesis with yields up to 88 %. These products were purified
      through the convenient washing with appropriate solvents and isolated in good
      yield. In addition, 27 amide or urea derivatives of anilines were also prepared.
      Bioassay data showed that some of the synthesized compounds displayed selective
      insecticidal bioactivities against tested pests.

PMID- 24281926
TI  - [Foreign language patients].

PMID- 24281927
TI  - [Ischemic priapism - how successful is distal shunt surgery?].

PMID- 24281928
TI  - [Radical cystectomy - open or robot-assisted?].

PMID- 24281929
TI  - [PREFERE study accepting patients throughout the country].

PMID- 24281930
TI  - [Percutaneous nephrolithotomy - tranexamic acid reduces blood loss].

PMID- 24281931
TI  - [Continent urinary diversion - ureterosigmoidostomy: 50 years follow-up].

PMID- 24281932
TI  - [PROBASE study - optimizing PSA screening].

PMID- 24281933
TI  - [Clean storage of the tip of a catheter bag].

PMID- 24281935
TI  - [Relinquishing the practice permit - revoking a practice closure request involves
      high hurdles].

PMID- 24281934
TI  - [Communication - the "difficult" patient].

PMID- 24281936
TI  - [Nocturia--an often misjudged problem].
AB  - Nocturia--waking up during the night due to the urge to urinate and empty the
      bladder--is a serious problem for affected patients. In the past decades,
      nocturia has been primarily regarded as an irritative symptom of benign prostate
      hyperplasia (BPH). This symptom is however frequently not influenced by different
      BPH treatments. In the last couple of years one has come to the conclusion that
      the prostate is less involved and in part responsible for the symptoms since
      women are also frequently affected. For these reasons nocturia is looked at
      differently. It is a highly prevalent symptom which neither qualitatively nor
      quantitative differs between men and women. Many factors lead to nocturia. The
      following diseases are involved: coronary heart disease, diabetes mellitus or
      insipidus, lower urinary tract symptoms (LUTS), states of anxiety or insomnia as
      well as behavioural and environmental factors. Nocturia can be categorised in
      nocturnal polyuria (overproduction of nightly urine) or a diminished bladder
      capacity or a combination of both. These entities can be easily differentiated by
      arithmetic analysis, e.g., a 48-hour voiding diary. Only recently nocturia has
      been classified according to the aetiology and pathogenesis, making a
      differentiated treatment possible. However, even in the cases in which the
      underlying cause cannot be found behavioural changes can help. Nevertheless,
      pharmacological treatments are inevitable. Medical treatments include:
      desmopressin, anticholinergics and antimuscarinics, general-medical measures like
      support stockings, different time for the intake of diuretics or in specific
      cases the nasal CPAP artificial respiration (continuous positive airway
      pressure). In spite of the partly high effectiveness of these measures, treatment
      should be customised taking possible side effects in account.

PMID- 24281938
TI  - Magnetogenesis in water induced by a chemical analyte.
AB  - This Minireview aims to shed light on the emergent field of inducing a change in
      the magnetic properties of a solution-phase sample by exposing it to a chemical
      analyte. A considerable body of knowledge exists on materials that alter their
      magnetic characteristics after a change in the surrounding physical conditions
      and a number of cases even exist of solution-phase samples that do so under these
      same circumstances. However, examples of dissolved molecules or particles that
      react in this fashion under constant conditions and in response to an analyte are
      limited. Although some cases in organic solvents are discussed, the emphasis of
      this Minireview is on water. Our aim is to provide the reader with guidelines for
      designing new magnetogenic probes for the detection of the desired chemical
      analyte. 

PMID- 24281939
TI  - Patient health incentives: ethical challenges and frameworks.
AB  - BACKGROUND: Patient incentives for encouraging healthy behavior raise a number of
      ethical concerns: Do they target the vulnerable? Do they involve psychological
      manipulation? Do they undermine intrinsic motivation? PURPOSE: To the purpose of
      this paper is to provide an overview of ethical challenges raised by patient
      incentives and incentive programs and develop a systematic approach to
      understanding and analyzing these ethical challenges. METHOD: Ethical
      considerations raised by patient incentives can be broadly grouped into two
      kinds: medical ("patient-oriented") and public health ("constituent-oriented")
      concerns. Ethical frameworks suitable to these kinds of concerns are explored.
      RESULTS: Two ethical frameworks are applied to the challenges raised by patient
      incentives: (1) Incentives are assessed in terms of personal and social
      responsibility for health; and (2) incentives are assessed as elements of
      normatively structured clinical relationships (e.g., the traditional patient
      clinician relationship). CONCLUSION: A better understanding of ethical concerns
      and the resources available within the personal responsibility and clinical
      encounter frameworks suggest complementary guidance may be available for
      approaching many of the ethical issues raised by patient incentives.

PMID- 24281940
TI  - Age and obesity alter the relationship between femoral articular cartilage
      thickness and ambulatory loads in individuals without osteoarthritis.
AB  - Articular cartilage is sensitive to mechanical loading, so increased risk of
      osteoarthritis in older or obese individuals may be linked to changes in the
      relationship between cartilage properties and extrinsic joint loads. A positive
      relationship has been reported between ambulatory loads and cartilage thickness
      in young individuals, but whether this relationship exists in individuals who are
      older or obese is unknown. This study examined the relationship between femoral
      cartilage thickness and load, measured by weight * height and the peak adduction
      moment, in young normal-weight (28 subjects, age: 28.0 +/- 3.8 years, BMI: 21.9
      +/- 1.9 kg/m(2)), middle-aged normal-weight (27 subjects, 47.0 +/- 6.5 years,
      22.7 +/- 1.7 kg/m(2)), young overweight/obese (27 subjects, 28.4 +/- 3.6 years,
      33.3 +/- 4.6 kg/m(2)), and middle-aged overweight/obese (27 subjects, 45.8 +/-
      7.2 years, 31.9 +/- 4.4 kg/m(2)) individuals. On the lateral condyle, cartilage
      thickness was positively correlated with weight * height for all groups (R(2)  =
      0.26-0.20) except the middle-aged overweight/obese. On the medial condyle, weight
      * height was significantly correlated only in young normal-weight subjects (R(2) 
      = 0.19), as was the case for the correlation between adduction moment and medial
      lateral thickness ratio (R(2)  = 0.20). These results suggest that aging and
      obesity are both associated with a loss of the positive relationship between
      cartilage thickness and ambulatory loads, and that the relationship is dependent
      on the compartment and whether the load is generated by body size or subject
      specific gait mechanics.

PMID- 24281941
TI  - Physical activity (PA) and sleep among children and adolescents with cancer.

PMID- 24281942
TI  - Morphine-induced apoptosis in the ventral tegmental area and hippocampus after
      the development but not extinction of reward-related behaviors in rats.
AB  - Some data suggest that morphine induces apoptosis in neurons, while other
      evidences show that morphine could have protective effects against cell death. In
      this study, we suggested that there is a parallel role of morphine in reward
      circuitry and apoptosis processing. Therefore, we investigated the effect of
      morphine on modifications of apoptotic factors in the ventral tegmental area
      (VTA) and hippocampus (HPC) which are involved in the reward circuitry after the
      acquisition and extinction periods of conditioned place preference (CPP). In
      behavioral experiments, different doses of morphine (0.5, 5, and 10 mg/kg) and
      saline were examined in the CPP paradigm. Conditioning score and locomotor
      activity were recorded by Ethovision software after acquisition on the post
      conditioning day, and days 4 and 8 of extinction periods. In order to investigate
      the molecular mechanisms in each group, we then dissected the brains and measured
      the expression of apoptotic factors in the VTA and HPC by western blotting
      analysis. All of the morphine-treated groups showed an increase of apoptotic
      factors in these regions during acquisition but not in extinction period. In the
      HPC, morphine significantly increased the ratio of Bax/Bcl-2, caspases-3, and
      PARP by the lowest dose (0.5 mg/kg), but, in the VTA, a considerable increase was
      seen in the dose of 5 mg/kg; promotion of apoptotic factors in the HPC and VTA
      insinuates that morphine can affect the molecular mechanisms that interfere with
      apoptosis through different receptors. Our findings suggest that a specific
      opioid receptor involves in modification of apoptotic factors expression in these
      areas. It seems that the reduction of cell death in response to high dose of
      morphine in the VTA and HPC may be due to activation of low affinity opioid
      receptors which are involved in neuroprotective features of morphine. 

PMID- 24281943
TI  - Expression and cell distribution of neuroglobin in the brain tissue after
      experimental subarachnoid hemorrhage in rats: a pilot study.
AB  - Neuroglobin (Ngb) is a member of the globin superfamily expressed mainly in the
      nervous system and retina of vertebrates. Accumulated evidence has clearly
      demonstrated that Ngb has a neuro-protective role enhancing cell viability under
      hypoxia and other types of oxidative stress. It was suggested that oxidant stress
      could play an important role in neuronal injury after subarachnoid hemorrhage
      (SAH). The present study aims to examine the expression of Ngb in the temporal
      cortex and its cellular localization after SAH. We used a prechiasmatic cistern
      model of SAH. Ngb expression was examined at 3, 6, 12, 24, 48, and 72 h after SAH
      by western blot analysis and real-time polymerase chain reaction (PCR).
      Immunohistochemistry and immunofluorescence were performed to detect the
      localization of Ngb. Real-time PCR demonstrated that Ngb mRNA levels increased
      from 3 h after SAH, peaked at 6 h. Western blot showed Ngb protein levels were
      significantly increased in SAH groups in the temporal cortex and reached the peak
      at 24 h after SAH. The immunohistochemical staining demonstrated that Ngb was
      weakly expressed in the cortex in the control group while the enhanced expression
      of Ngb could be detected in the SAH groups. In addition, immunofluorescence
      results revealed that the over-expressed Ngb was located in the neuronal and
      microglia cell cytoplasm. These findings indicated that Ngb might play an
      important neuro-protective effect after SAH. 

PMID- 24281944
TI  - Safety of bevacizumab in patients with malignant gliomas: a systematic review.
AB  - Angiogenesis has recently become a major target for the development of new
      antineoplastic drugs. The most serious adverse events linked to angiogenesis
      inhibitors are venous or arterial thromboembolism and haemorrhage. Thus, there is
      need to define with more certainty the impact of these new drugs in terms of
      adverse effects in neurological patients. The aim of the study is to assess the
      risk of venous thromboembolism (VTE) and bleeding in patients with malignant
      gliomas treated with bevacizumab with or without concomitant anticoagulant
      therapy. A review of published literature was performed in Medline, from which
      476 records were identified. A total of 27 full-text articles, including
      retrospective analyses, retrospective reviews, and open label trials, were
      assessed for eligibility. The investigated drugs included bevacizumab alone,
      bevacizumab plus chemotherapy with/without concomitant radiation therapy; only
      two articles dealt with bevacizumab in association with anticoagulant treatment.
      A total of 2,208 patients with malignant gliomas, were identified and included in
      the analysis. From data it appears that patients receiving bevacizumab had a
      major risk of developing VTE that increased when bevacizumab is associated with
      radio-chemotherapy (4.27 vs 7.46 %). Regarding bleeding, data showed that
      patients treated with anticoagulant had a significantly increased risk of severe
      central nervous system (CNS) bleeding compared to patients not receiving
      anticoagulant therapy (0.6 vs 8.2 %). The use of bevacizumab combined with chemo
      radiotherapy seems to be associated with a higher risk for VTE compared to
      patients receiving antiangiogenic therapy alone. The associated use of
      anticoagulants and bevacizumab far increases the risk of developing CNS and non
      CNS bleeding higher than grade 3, compared to patients receiving bevacizumab
      alone.

PMID- 24281945
TI  - Positive sharp waves in the EEG of children and adults.
AB  - Interictal epileptiform discharges (IEDs) with negative polarity have been
      extensively studied in the EEG literature. However, little attention has been
      drawn to IED with positive polarity [positive sharp waves (PSWs)]. In this paper,
      we discuss pathophysiological, neuroimaging, and clinical correlates of this
      pattern in a heterogeneous group of children and adults who demonstrated PSW in
      their scalp EEG. We prospectively reviewed the EEGs of 1,250 patients from a
      heterogeneous population over a period of 1 year. Thirty-one patients had PSW in
      their EEG. We documented EEG parameters as well as demographic, clinical, and
      neuroimaging data. Statistical analysis was performed to correlate the
      aforementioned data. The analysis showed that PSW is an epileptogenic pattern
      with localizing significance, occurring primarily in the younger age groups.
      Furthermore, there was a strong association of PSW with chronic and/or static CNS
      pathology, in particular, congenital CNS anomalies, often accompanied by
      psychomotor retardation. Patients with "multifocal'' PSW invariably exhibited
      severe intellectual and motor deficits associated consistently with a variety of
      congenital CNS insults. PSW is a rare and under-reported EEG abnormality which,
      similar to negative IED, signifies focal epileptogenecity. The presence of PSW
      should prompt neuroimaging studies to investigate an associated chronic/static
      CNS pathology, in particular, congenital CNS anomalies. This association is
      particularly strong when PSW is multifocal in which case patients present with
      severe intellectual and motor deficits.

PMID- 24281947
TI  - Sonographic evaluation of hip joint effusion in osteoarthritis with correlation
      to radiographic findings.
AB  - PURPOSE: Hip joint effusion is expected in rapidly destructive osteoarthritis, a
      diagnosis often only made retrospectively at the end stage of the disease. This
      study assesses whether the presence of an effusion identified during routine
      ultrasound-guided hip injection may suggest a more aggressive process such as
      rapidly destructive osteoarthritis. METHODS: After the observation of 10 index
      cases of rapidly destructive osteoarthritis in patients who presented with a
      joint effusion on ultrasound, we retrospectively reviewed 94 hips from 89
      patients who underwent ultrasound-guided hip injection for pain. Preinjection
      longitudinal ultrasound images of the anterior capsule adjacent to the femoral
      neck and inferior to the femoral head were reviewed to determine if a joint
      effusion was present and the size of the effusion if one was there. Comparison of
      effusion size was then made between those hips that had a clinical and
      radiographic diagnosis of osteoarthritis and those who had rapidly destructive
      osteoarthritis by comparing the severity of joint effusion, if one was present.
      RESULTS: Patients with rapidly destructive osteoarthritis were more likely to
      have a large joint effusion 60% (3/5) than were those with osteoarthritis 6.7%
      (6/89) (p = 0.013). CONCLUSIONS: Large joint effusions identified sonographically
      correlate well with radiographic findings of rapidly destructive osteoarthritis.
      Given rapid onset and severity of the disease, when a large joint effusion is
      identified on routine hip intervention, patients should be forewarned of the
      potential for this disease process.

PMID- 24281946
TI  - Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading
      pathogens.
AB  - Macrophages are among the first cellular actors facing the invasion of
      microorganisms. These cells are able to internalize pathogens and destroy them by
      means of toxic mediators, many of which are produced enzymatically and have
      strong oxidizing capacity. Indeed, macrophages count on the NADPH oxidase complex
      activity, which is triggered during pathogen invasion and leads to the production
      of superoxide radical inside the phagosome. At the same time, the induction of
      nitric oxide synthase results in the production of nitric oxide in the cytosol
      which is able to readily diffuse to the phagocytic vacuole. Superoxide radical
      and nitric oxide react at diffusion controlled rates with each other inside the
      phagosome to yield peroxynitrite, a powerful oxidant capable to kill micro
      organisms. Peroxynitrite toxicity resides on oxidations and nitrations of
      biomolecules in the target cell. The central role of peroxynitrite as a key
      effector molecule in the control of infections has been proven in a wide number
      of models. However, some microorganisms and virulent strains adapt to survive
      inside the potentially hostile oxidizing microenvironment of the phagosome by
      either impeding peroxynitrite formation or rapidly detoxifying it once formed. In
      this context, the outcome of the infection process is a result of the interplay
      between the macrophage-derived oxidizing cytotoxins such as peroxynitrite and the
      antioxidant defense machinery of the invading pathogens.

PMID- 24281948
TI  - Incisional hernia rate 3 years after midline laparotomy.
AB  - BACKGROUND: Incisional hernia is the most frequent long-term complication after
      visceral surgery, with an incidence of between 9 and 20 per cent 1 year after
      operation. Most controlled studies provide only short-term follow-up, and the
      actual incidence remains unclear. This study evaluated the incidence of
      incisional hernia up to 3 years after midline laparotomy in two prospective
      trials. METHODS: Three-year follow-up data from the ISSAAC (prospective,
      multicentre, historically controlled) and INSECT (randomized, controlled,
      multicentre) trials focused on the rate of incisional hernia 1 and 3 years after
      surgery. Differences between the two groups were compared using t tests for
      continuous data and the chi2 test for categorical data. RESULTS: Analysis of 775
      patients included in the two trials suggested that the incisional hernia rate
      increased significantly from 12.6 per cent at 1 year to 22.4 per cent 3 years
      after surgery (P < 0.001), a relative increase of more than 60 per cent.
      CONCLUSION: This follow-up of two trials demonstrated that 1 year of clinical
      follow-up for detection of incisional hernia is not sufficient; follow-up for at
      least 3 years should be mandatory in any study evaluating the rate of
      postoperative incisional hernia after midline laparotomy.

PMID- 24281949
TI  - Dexamethasone-loaded hydroxyapatite enhances bone regeneration in rat calvarial
      defects.
AB  - A combination of bioceramics and osteogenic factors is potentially useful for
      bone regeneration applications. In the present study, hydroxyapatite particles
      (HA) were loaded with dexamethasone (Dex) and then characterized using SEM and
      drug release study. The bone regeneration ability of Dex-loaded HA (Dex/HA) was
      investigated in a rat critical size bone defect using digital mammography,
      multislice spiral-computed tomography (MSCT) imaging, and histological analysis.
      The HA and Dex/HA showed nano and micro-scale morphology with a nearly homogenous
      distribution of diameter. In addition, about 90 % of the drug was released from
      Dex/HA over a period of three days. After 8 weeks of implantation in rat
      calvarial defects, no sign of inflammation or complication was observed at the
      site of surgery. According to digital mammography and MSCT, Dex/HA showed the
      highest bone regeneration in rat bone defects compared to those received drug
      free HA. Histological studies confirmed these data and showed osteointegration to
      the surrounding tissue. Taking all together, it was demonstrated that Dex/HA can
      be used as an appropriate synthetic graft for bone tissue engineering
      applications. These newly developed bioceramics can be used as new bone graft
      substitutes in orthopaedic surgery and is capable of enhancing bone regeneration.

PMID- 24281950
TI  - A glycine-rich RNA-binding protein affects gibberellin biosynthesis in
      Arabidopsis.
AB  - The RNA-binding protein Arabidopsis thaliana glycine-rich RNA-binding protein 7
      (AtGRP7) regulates the steady-state abundance of numerous target transcripts in
      A. thaliana. Here we show that the GA1 and GA2 transcripts encoding the first
      enzymes of the gibberellin biosynthetic pathway are expressed at reduced levels
      in transgenic plants ectopically over-expressing AtGRP7 (AtGRP7-ox plants).
      Furthermore, the levels of the bioactive phytohormone GA4 as well as of several
      intermediates of the GA biosynthetic pathway are reduced in AtGRP7-ox plants. The
      transgenic plants show a reduced length of the vegetative stem. The application
      of exogenous GA largely reverses the phenotype by increasing the number of
      vegetative internodes. AtGRP7-ox plants flower with fewer leaves than wt plants,
      suggesting that the floral promotive effect of AtGRP7 bypasses the effect of a
      reduced GA level in AtGRP7-ox plants. Upon GA treatment, AtGRP7-ox plants flower
      only slightly earlier than wild type plants. Thus, exogenous GA has only a small
      additional effect in reducing the number of leaves at the onset of flowering in
      AtGRP7-ox plants.

PMID- 24281951
TI  - Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.
AB  - PURPOSE: A practical, noninvasive method is needed to measure the extracellular
      pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have
      optimized a biomedical imaging method, termed acidoCEST MRI, to provide
      noninvasive assessments of tumor pHe in preclinical models of mammary carcinoma.
      METHODS: A CEST-FISP MRI method was optimized to detect the chemical exchange
      saturation transfer (CEST) of two amide protons of a clinically approved CT
      contrast agent, iopromide. The ratio of the two CEST effects was used to measure
      pH. Routes of administration of iopromide were evaluated to ensure sufficient
      delivery of the agent to the tumor. The optimized acidoCEST MRI method was then
      used to evaluate the change in tumor pHe following alkalinizing bicarbonate
      treatment. RESULTS: The acidoCEST MRI protocol measured pH between 6.2 and 7.2 pH
      units. Greater delivery of iopromide was shown to improve the precision of the
      measurement of tumor pHe, but the agent did not influence the tumor pHe.
      AcidoCEST MRI was used to longitudinally monitor the effect of bicarbonate
      treatment on the pHe of tumors and bladders. CONCLUSION: This study demonstrates
      that an optimized acidoCEST MRI method is a practical, noninvasive method for
      assessing changes in tumor acidosis.

PMID- 24281954
TI  - [How to join interdisciplinary research and health care].

PMID- 24281955
TI  - [Diabetic foot syndrome].

PMID- 24281952
TI  - Non-native N-aroyl L-homoserine lactones are potent modulators of the quorum
      sensing receptor RpaR in Rhodopseudomonas palustris.
AB  - Quorum sensing (QS) is a process by which bacteria use low-molecular-weight
      signaling molecules (or autoinducers) to assess their local population densities
      and alter gene expression levels at high cell numbers. Many Gram-negative
      bacteria use N-acyl L-homoserine lactones (AHLs) with aliphatic acyl groups as
      signaling molecules for QS. However, bacteria that utilize AHLs with aroyl acyl
      groups have been recently discovered; they include the metabolically versatile
      soil bacterium Rhodopseudomonas palustris, which uses p-coumaroyl HL (p-cAHL) as
      its QS signal. This autoinducer is especially unusual because its acyl group is
      believed to originate from a monolignol (i.e., p-coumarate) produced exogenously
      by plants in the R. palustris environment, rather than through the endogenous
      fatty acid biosynthesis pathway like other native AHLs. As such, p-cAHL could
      signal not only bacterial density, but also the availability of an exogenous
      plant-derived substrate and might even constitute an interkingdom signal. Like
      other Gram-negative bacteria, QS in R. palustris is controlled by the p-cAHL
      signal binding its cognate LuxR-type receptor, RpaR. We sought to determine if
      non-native aroyl HLs (ArHLs) could potentially activate or inhibit RpaR in R.
      palustris, and thereby modulate QS in this bacterium. Herein, we report the
      testing of a set of synthetic ArHLs for RpaR agonism and antagonism by using a R.
      palustris reporter strain. Several potent non-native RpaR agonists and
      antagonists were identified. Additionally, the screening data revealed that lower
      concentrations of ArHL are required to strongly agonize RpaR than to antagonize
      it. Structure-activity relationship analyses of the active ArHLs indicated that
      potent RpaR agonists tend to have sterically small substituents on their aryl
      groups, most notably in the ortho position. In turn, the most potent RpaR
      antagonists were based on either the phenylpropionyl HL (PPHL) or the
      phenoxyacetyl HL (POHL) scaffold, and many contained an electron-withdrawing
      group at either the meta or para positions of the aryl ring. To our knowledge,
      the compounds reported herein represent the first abiotic chemical modulators of
      RpaR, and more generally, the first abiotic ligands capable of intercepting QS in
      bacteria that utilize native ArHL signals. In view of the origins of the p-cAHL
      signal in R. palustris, the largely unknown role of QS in this bacterium, and R.
      palustris' unique environmental lifestyles, we anticipate that these compounds
      could be valuable as chemical probes to study QS in R. palustris in a range of
      fundamental and applied contexts. 

PMID- 24281956
TI  - [Hyperandrogenemia].

PMID- 24281957
TI  - [New data on diabetes and dementia].

PMID- 24281958
TI  - [Primary CNS lymphoma].

PMID- 24281959
TI  - [Influenza].
AB  - Yearly epidemics and occasional pandemics with Influenza have been observed for
      several hundred years. During the last pandemic the reported deaths due to
      confirmed influenza was lower than expected. New epidemiologic analyses
      demonstrate that the severity has probably been underestimated. In addition,
      cohort data from severely ill patients support the use of neuraminidase
      inhibitors in complicated influenza infections. Due to the increasing divergence
      of the two circulation Influenza B strains, WHO has recommended a quadrivalent
      vaccine. Several quadrivalent vaccines have been successfully developed. The
      association of adjuvanted 2009 pandemic vaccine and narcolepsy is still debated,
      new data from several countries contribute to this discussion. Avian viruses have
      fuelled all pandemics since 1918. Surveillance of avian influenza viruses is thus
      regarded essential for pandemic preparedness. In 2013 a new avian influenza
      virus, H7N9 has cause human infections and deaths. This new strain has low
      pathogenicity in birds and thus surveillance is especially challenging. 

PMID- 24281960
TI  - [Neurological aspects of intensive care: stroke, intracerebral hemorrhage,
      meningitis, status epilepticus].

PMID- 24281961
TI  - [Pacemaker, cardiac resynchonisation, implantable cardioverter/defibrillator,
      event monitoring].

PMID- 24281962
TI  - [Primary arterial hypertension. Update 2013].

PMID- 24281963
TI  - [Allergic diseases: what is new?].

PMID- 24281964
TI  - [Soft tissue rheumatic syndromes and treatment of pain].

PMID- 24281965
TI  - [Diagnosis and differential diagnosis of panceatic lesions].

PMID- 24281966
TI  - [53-year-old patient with hypotension].

PMID- 24281967
TI  - [German S3-guideline colorectal carcinoma].

PMID- 24281968
TI  - [Unstable angina pectoris--combination of an epicardial stenosis and a Prinzmetal
      spasm].
AB  - HISTORY AND ADMISSION FINDINGS: A 61-year-old man presented with recurrent angina
      pectoris at rest for 3 days. The medical history revealed hypertension and an
      elevated cholesterol level as cardiovascular risk factors. INVESTIGATIONS: The
      physical examination revealed no pathological findings. ECG at admission showed
      no signs of ischemia, while high-sensitive Troponin T was slightly elevated.
      Echocardiography showed diastolic dysfunction and biatrial dilatation. TREATMENT
      AND COURSE: During another episode of angina at rest, ECG showed T-wave inversion
      in lead aVL. Therefore, coronary angiography was performed. At the beginning of
      the examination the patient complained of angina at rest and ECG showed ST
      elevation in the inferior leads. Coronary angiography revealed a subtotal
      stenosis in the middle part of the RCA. After intracoronary nitroglycerin
      injection there was a high-grade stenosis in this region. An intracoronary
      acetycholin provocation test was performed which reproduced a focal spasm in the
      area of the RCA stenosis with simultaneous changes in the ECG and reproduction of
      the patient's unusual angina. After implantation of a bare metal stent a
      subsequent ACH-test did not elicit any further coronary spasm. Four weeks after
      the procedure the patient had no further complaints under medical treatment.
      CONCLUSION: This case illustrates a patient with a focal Prinzmetal-type spasm
      with ST-elevation on top of a high-grade stenosis of the right coronary artery as
      an explanation for the unstable angina. Coronary spasm of the Prinzmetal-type can
      occur in vessels with epicardial stenosis as well as in vessels without stenosis.
      In some cases focal coronary spasm can be prevented by the implantation of a
      stent.

PMID- 24281969
TI  - [Pharmacotherapy of sleep disorders in elderly patients].
AB  - Elderly patients often suffer from sleep disturbances. Disorders are mostly
      caused by medical, neurological or psychiatric diseases and multimorbidity. The
      treatment of the underlying disease should therefore be prioritised. In the
      symptomatic treatment of insomnia cognitive-behavioural strategies are
      established. Drug therapy should be considered only if non-pharmacological
      treatments fail. Most hypnotics have a poor risk-benefit ratio in older patients.
      In acute severe sleep disturbances prescription of short-acting benzodiazepines
      and nonbenzodiazepine hypnotics in low doses over a short period of time is
      acceptable. In patients suffering from chronic insomnia a treatment with sedative
      antidepressants can be considered keeping in mind possible adverse effects.
      Studies analysing the current status of care for elderly insomnia patients in
      Germany are limited. Analyses of health insurance data suggest that especially
      nursing home patients often use hypnotics. The treatment of sleep disorders in
      elderly patients must therefore be optimized in practice. 

PMID- 24281971
TI  - CLL/SLL diagnosed in an adolescent.
AB  - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a disease of
      older adults. Pediatric CLL/SLL is vanishingly rare in the literature. We present
      a case of CLL/SLL diagnosed in a 17-year-old male. The pathologic findings of
      this case were those of classic CLL/SLL with an ATM deletion, a characteristic
      genetic abnormality in CLL/SLL. Management guidelines for CLL/SLL are tailored to
      older adults making determination of the optimal therapy for this patient a
      unique challenge.

PMID- 24281972
TI  - Targeted bioimaging and photodynamic therapy nanoplatform using an aptamer-guided
      G-quadruplex DNA carrier and near-infrared light.

PMID- 24281973
TI  - Effects of post surface treatments including Er:YAG laser with different
      parameters on the pull-out bond strength of the fiber posts.
AB  - This study aims to evaluate the effects of Er:YAG laser irradiation under
      different power settings on the pull-out bond strengths of fiber-reinforced
      composite posts. The crowns of single-rooted 60 teeth were removed by separation
      and the root canals were cleaned and shaped. Root canals were filled and post
      spaces were prepared. Sixty fiber posts were divided into five groups according
      to surface treatment methods as follows: an untreated control group, a
      sandblasting-coated group, and three groups undergoing surface preparation with
      Er:YAG laser under three different power settings (150, 300, and 450 mJ at 10 Hz
      for 60 s at 100-MUs pulse duration). After root canal procedures, fiber posts
      were cemented to the root canal. After all of the specimens were set, pull-out
      tests were performed using a universal testing machine at a crosshead speed of 2
      mm/min. The data were analyzed using one-way ANOVA and Tukey post-hoc test (p <
      0.05). The pull-out strength values ranged between 5.26 and 6.76 Mpa. The lowest
      values were observed in the groups without surface treatment. Surface treatment
      applied by 4.5-W Er:YAG laser increased the pull-out bond strength compared to
      the control group (p < 0.05). 4.5-W Er:YAG laser irradiation increased the pull
      out bond strength of fiber posts to resin cement.

PMID- 24281974
TI  - Molecular versatility: the many faces and functions of noncoding RNA.

PMID- 24281975
TI  - Clinical implications of conduction abnormalities and arrhythmias after
      transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has become an established
      treatment option for patients with aortic stenosis at prohibitive risk to undergo
      surgical aortic valve replacement. Despite conveying obvious clinical benefits
      and a decreasing frequency of complications, the occurrence of new conduction
      abnormalities and arrhythmias remains an important issue. Generally considered a
      minor complication, they may have a profound impact on prognosis and quality of
      life after TAVI. Therefore the purpose of this review is to assess and discuss
      the available information on clinical implications of both new conduction
      abnormalities and arrhythmias after TAVI. 

PMID- 24281976
TI  - Impact of obesity and bariatric surgery on metabolism and coronary circulatory
      function.
AB  - Increases in intra-abdominal visceral adipose tissue have been widely appreciated
      as a risk factor for metabolic disorders such as dyslipidemia, hypertension,
      insulin resistance, and type 2 diabetes, whereas this is not the case for
      peripheral or subcutaneous obesity. While the underlying mechanisms that
      contribute to these differences in adipose tissue activity remain uncertain,
      increases in visceral fat commonly induce metabolic dysregulation, in part
      because of increased venous effluent of fatty acids and/or adipokines/cytokines
      to the liver. Increased body weight, paralleled by an increase in plasma markers
      of the insulin-resistance syndrome and chronic inflammation, is independently
      associated with coronary circulatory dysfunction. Recent data suggest that plasma
      proteins originating from the adipose tissue, such as endocannabinoids (EC),
      leptin, and adiponectin (termed adipocytes) play a central role in the regulation
      and control of coronary circulatory function in obesity. Positron emission
      tomography (PET) in concert with tracer kinetic modeling is a well established
      technique for quantifying regional myocardial blood flow at rest and in response
      to various forms of vasomotor stress. Myocardial flow reserve assessed by PET
      provides a noninvasive surrogate of coronary circulatory function. PET also
      enables the monitoring and characterization of coronary circulatory function in
      response to gastric bypass-induced weight loss in initially morbidly obese
      individuals, to medication and/or behavioral interventions related to weight,
      diet, and physical activity. Whether the observed improvement in coronary
      circulatory dysfunction via weight loss may translate to diminution in
      cardiovascular events awaits clinical confirmation. 

PMID- 24281977
TI  - Percutaneous mitral valve repair.
AB  - Nonsurgical treatment of clinically important mitral regurgitation (MR) has
      evolved tremendously over the past decade. Recent studies of percutaneous mitral
      valve repair procedures have shown that less invasive procedures are safe and can
      be effective in selected patients. MitraClip has been studied most extensively.
      The MitraClip is attached to the middle scallop of the mitral leaflets by a
      transseptal-transvascular approach. The device approximates the leaflets in an
      edge-to-edge percutaneous repair technique that diminishes MR, improves
      functional status, and improves left ventricular remodeling. The subgroup that
      has the most benefit includes patients with older age, poorer left ventricular
      function, and functional MR and is considered high risk for surgical valve
      replacement. Other novel percutaneous mitral valve therapies under investigation
      include indirect and direct annuloplasty, and ventricular remodeling devices. 

PMID- 24281979
TI  - Prototype phantoms for characterization of ultralow field magnetic resonance
      imaging.
AB  - PURPOSE: Prototype phantoms were designed, constructed, and characterized for the
      purpose of calibrating ultralow field magnetic resonance imaging (ULF MRI)
      systems. The phantoms were designed to measure spatial resolution and to quantify
      sensitivity to systematic variation of proton density and relaxation time, T1 .
      METHODS: The phantoms were characterized first with conventional magnetic
      resonance scanners at 1.5 and 3 T, and subsequently with a prototype ULF MRI
      scanner between 107 and 128 MUT . RESULTS: The ULF system demonstrated a 2-mm
      spatial resolution and, using T1 measurements, distinguished aqueous solutions of
      MnCl2 differing by 20 MUM  [Mn(2+) ]. CONCLUSION: The prototype phantoms proved
      well-matched to ULF MRI applications, and allowed direct comparison of the
      performance of ULF and clinical systems.

PMID- 24281978
TI  - IL-13Ralpha1 is a surface marker for M2 macrophages influencing their
      differentiation and function.
AB  - In this study, we examined the role IL-13 receptor alpha 1 (IL-13Ralpha1) plays
      in macrophage differentiation and function. The findings indicate that IL
      13Ralpha1 is expressed on the M2 but not on the M1 subset of macrophages and
      specifically heterodimerizes with the IL-4Ralpha chain to form a type II
      receptor, which controls the differentiation and function of these cells. Indeed,
      BM cells from IL-13Ralpha1(+/+) and IL-13Ralpha1(-/-) mice yield equivalent
      numbers of macrophages when cultured under M2 polarizing conditions. However, IL
      13Ralpha1(-/-) BM cells yield a much higher number of macrophages than IL
      13Ralpha1(+/+) BM cells when the differentiation is carried out under M1
      polarizing conditions. Further analyses indicated that macrophages that express
      IL-13Ralpha1 also display surface markers associated with an M2 phenotype. In
      addition, the IL-13Ralpha1(+) macrophages were highly efficient in phagocytizing
      zymosan bioparticles both in vitro and in vivo, and supported differentiation of
      naive T cells to a Th2 phenotype. Finally, when stimulated by IL-13, a cytokine
      that uses the heteroreceptor, the cells were able to phosphorylate STAT6
      efficiently. These previously unrecognized findings indicate that IL-13Ralpha1
      serves as a marker for M2 macrophages and the resulting heteroreceptor influences
      both their differentiation and function. 

PMID- 24281980
TI  - An evidence based approach to sports concussion: confronting the availability
      cascade.

PMID- 24281981
TI  - Carbetocin at elective Cesarean delivery: a sequential allocation trial to
      determine the minimum effective dose.
AB  - PURPOSE: The purpose of this study was to determine the intravenous dose of
      carbetocin required to produce effective uterine contraction in 90% of females
      (ED90) undergoing elective Cesarean delivery (CD) under spinal anesthesia.
      METHODS: We conducted a double-blind dose-finding study of carbetocin. Forty
      females undergoing elective CD received carbetocin intravenously upon delivery of
      the fetus. The dose of carbetocin for each patient was determined according to a
      biased-coin up-and-down sequential allocation scheme designed to cluster doses
      close to ED90. The initial dose was 10 MUg, with increments/decrements of 5 MUg.
      The anesthesiologist, obstetrician, and patient were blinded to the dose. The
      obstetrician assessed the uterine tone at one-minute intervals for five minutes
      after carbetocin administration. In case of unsatisfactory tone, additional
      uterotonics were administered. The primary outcome was requirement for additional
      intraoperative uterotonics. Secondary outcomes were postoperative requirement for
      additional uterotonics within 24 hr of delivery, estimated blood loss and side
      effects. RESULTS: The ED90 of carbetocin was 14.8 MUg (95% confidence interval
      13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no
      requirement of additional intraoperative uterotonics. Two patients (5%) required
      postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood
      loss was 786 (403) mL and the overall incidence of hypotension (decrease in
      systolic blood pressure >= 20% baseline) was 37.5%. CONCLUSION: Based on our
      study, the ED90 of carbetocin at elective CD is less than one-fifth the currently
      recommended dose of 100 MUg. This study was registered at clinicaltrials.gov (NCT
      01651130).

PMID- 24281982
TI  - A multiemitter localization comparison of 3D superresolution imaging modalities.
AB  - Single-molecule localization-based superresolution imaging is complicated by
      emission from multiple emitters overlapping at the detector. The potential for
      overlapping emitters is even greater for 3D imaging than for 2D imaging due to
      the large effective "volume" of the 3D point spread function. Overlapping
      emission can be accounted for in the estimation model, recovering the ability to
      localize the emitters, but with the caveat that the localization precision has a
      dependence on the amount of overlap from other emitters. Whether a particular 3D
      imaging modality has a significant advantage in facilitating the position
      estimation of overlapping emitters is investigated. The variants of two commonly
      used and easily implemented imaging modalities for 3D single-molecule imaging are
      compared: astigmatic imaging; dual focal plane imaging; and the combination of
      the two approaches, dual focal plane imaging with astigmatism. The Cramer-Rao
      lower bound is used to quantify the multiemitter estimation performance by
      calculating the theoretical best localization precision under a multiemitter
      estimation model. The performance of these 3D modalities is investigated under a
      wide range of conditions including various distributions of collected photons per
      emitter, background counts, pixel sizes, and camera readout noise values.
      Differences between modalities are small and it is therefore concluded that
      multiemitter fitting performance should not be a primary factor in selecting
      between these modalities. 

PMID- 24281983
TI  - Diagnosis of sirenomelia in the first trimester.
AB  - Sirenomelia or "mermaid syndrome" is a rare congenital abnormality with an
      incidence of 1 in 60,000. We report a case diagnosed in the first trimester using
      two-dimensional, three-dimensional, and color Doppler ultrasound. With increasing
      emphasis on early diagnosis of fetal abnormalities, this case highlights the
      importance of looking for anomalies in the first trimester itself. In fact, the
      diagnosis of sirenomelia should be easier in the first trimester as severe
      oligohydramnios in later gestation hampers vision.

PMID- 24281984
TI  - Upper extremity deep vein thrombosis in hospitalized patients: a descriptive
      study.
AB  - Increasingly, there is a focus on the prevention of hospital-acquired conditions
      including venous thromboembolism. Many studies have evaluated pulmonary embolism
      and lower extremity deep vein thrombosis, but less is known about upper extremity
      deep vein thrombosis (UEDVT) in hospitalized patients. The objective of this
      study was to describe UEDVT incidence, associated risks, outcomes, and management
      in our institution. Using an information technology tool, we reviewed records of
      all symptomatic adult inpatients diagnosed with UEDVT at an academic tertiary
      center between September 2011 and November 2012. Fifty inpatients were diagnosed
      with 76 UEDVTs. Their mean age was 49 years; 70% were men. Sixteen percent had a
      history of venous thromboembolism; 20% had a history of malignancy. The mean
      length of stay (LOS) was 24.6 days (range, 2-91 days); 50% were transferred from
      outside hospitals. Thirty-eight percent of UEDVTs were in internal jugular veins,
      21% in axillary veins, and 25% in brachial veins. Forty-four percent of patients
      had UEDVT associated with central venous catheters (CVCs). During
      hospitalization, 78% were fully anticoagulated; 75% of survivors at discharge.
      Only 38% were discharged to self-care; 10% died during hospitalization. Patients
      with UEDVT were more likely to have CVCs, malignancy, and severe infection. Many
      patients were transferred critically ill with prolonged LOS and high in-hospital
      mortality. Most UEDVTs were treated even in the absence of concurrent lower
      extremity deep vein thrombosis or pulmonary embolism. Additional research is
      needed to modify risks and optimize outcomes. Journal of Hospital Medicine
      2014;9:48-53. (c) 2013 Society of Hospital Medicine. 

PMID- 24281985
TI  - Evaluation of synthetic osteochondral implants.
AB  - This translational animal model study was designed to assess function, bone
      ingrowth and integration, and joint pathology associated with two different
      synthetic, bilayered osteochondral implants over a 3-month period after
      implantation into the femoral condyles of dogs. SynACart-Titanium (n = 6) and
      SynACart-PEEK (n = 6) (Arthrex, Naples, FL, and Sites Medical, Columbia City, IN)
      implants were press-fit into the lateral or medial femoral condyle (alternating
      location) of purpose-bred adult research dogs. Dogs were humanely euthanized 3
      months after surgery and the operated knees were assessed radiographically,
      arthroscopically, grossly, and histologically. Based on all assessments, both
      types of implants were well tolerated and safe with no evidence for infection,
      migration, or rejection. Half of the SynACart-PEEK implants showed radiographic
      and histologic evidence of poor incorporation with all of these being in the
      lateral femoral condyle. SynACart-Titanium implants were considered effective in
      terms of integration into bone, lack of damage to surrounding and apposing
      articular cartilage, and maintenance of implant integrity and architecture for
      the duration of the study. 

PMID- 24281986
TI  - Click to release: instantaneous doxorubicin elimination upon tetrazine ligation.

PMID- 24281987
TI  - Unmasking translucent protein particles by improved micro-flow imagingTM
      algorithms.
AB  - Micro-flow imaging (MFI(TM) ) is an increasingly important technique for the
      characterization of subvisible particles during the development of
      biopharmaceutical products. Protein particles are highly variable in size,
      appearance, and translucency posing challenges to optical detection techniques.
      We have developed a set of standard statistical tests applicable for routine
      evaluation of MFITM particle dataset quality. The tests evaluate the spatial
      randomness of particles using nearest neighbor and quadrat analysis. Using case
      studies of stressed antibody samples, we demonstrate how the tests uncover
      fragmentation artifacts and uneven detector sensitivity for translucent
      particles. To improve the detection of translucent particles, a new local pixel
      intensity variance particle detection algorithm has been developed. The improved
      algorithm significantly decreases fragmentation artifacts, and also increases
      sensitivity toward translucent particles in general. Our results highlight
      current limitations and the potential for improvements in the optical detection
      techniques for subvisible protein aggregates.

PMID- 24281988
TI  - Replacing tin in lactide polymerization: design of highly active germanium-based
      catalysts.
AB  - Most germane: Hexacoordinate germanium(IV) species exhibit unprecedented
      activities, yet controlled behavior, as initiators for the ring-opening
      polymerization of rac-lactide to form polylactide polymers. 

PMID- 24281990
TI  - Commentary: thinking through public health genomics.

PMID- 24281989
TI  - Congenital fibrosarcoma of the bowel: sonographic description of a rare case of
      neonatal intestinal obstruction.
AB  - A case of localization in the bowel of congenital fibrosarcoma (a rare soft
      tissue tumor usually occurring in the extremities) causing intestinal obstruction
      in a newborn girl is described. A focal thickening of the ileal wall with
      features mimicking intussusception was identified at sonography; the final
      diagnosis was achieved by means of molecular analysis after surgical removal of
      the mass.

PMID- 24281991
TI  - Crowding alters the dynamics and the length of RecA nucleoprotein filaments in
      RecA-mediated strand exchange.
AB  - Crowd impact: Molecular crowding effects of bovine serum albumin and
      poly(ethylene glycol) on the Escherichia coli RecA-mediated strand exchange
      reaction are quantified by using a single-molecule outgoing strand experiment and
      magnetic pull-down and ATPase assays. The alterations of the biochemical
      parameters of this complex enzymatic reaction in such crowded environments are
      discussed. 

PMID- 24281992
TI  - CORR Insights(r): Long-term results and bone remodeling after THA with a short,
      metaphyseal-fitting anatomic cementless stem.

PMID- 24281993
TI  - Protective effect of vanadyl sulfate on skin injury in streptozotocin-induced
      diabetic rats.
AB  - The aim of the present study was to investigate the effect of vanadyl sulfate
      supplementation on the skin tissues of diabetic and control rats. In this study,
      6-6.5 months old male Swiss albino rats were used. The animals were randomly
      divided into the following four groups: group I, control (nondiabetic intact
      animals); group II, vanadyl sulfate control; group III, streptozotocin (STZ)
      diabetic animals and group IV, STZ-diabetic animals given vanadyl sulfate. The
      animals were made diabetic by intraperitoneal injection of a single dose of 65
      mg/kg STZ in 0.01 M citrate buffer (pH = 4.5). From day 1 to day 60, 100 mg/kg
      vanadyl sulfate was given daily by gavage technique to one of the control and
      diabetic groups. Body weights and blood glucose levels were estimated on
      experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken,
      glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and
      protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione-S
      transferase (GST) activities were determined. Blood glucose, skin LPO and NEG
      levels increased, but skin GSH levels and CAT, SOD and GST activities decreased
      in the STZ group. Treatment with vanadyl sulfate reversed these effects. The
      present study showed that vanadyl sulfate exerted antioxidant properties and may
      prevent skin damage caused by diabetes. 

PMID- 24281994
TI  - Factors affecting sonographic preoperative local staging of endometrial cancer.
AB  - OBJECTIVES: To identify major factors in the under- and overestimation of
      cervical and myometrial invasion by endometrial cancer at preoperative staging by
      ultrasound. METHODS: This prospective study involved all patients with
      histologically confirmed endometrial cancer referred consecutively for surgical
      staging between January 2009 and December 2011. All patients underwent
      transvaginal ultrasound examination, obtaining metric and perfusion data, and the
      results were compared with final histology: myometrial invasion was defined at
      histology in the final pathology report as being either < or >= 50%, while
      cervical stromal invasion was reported as being either present or absent, and
      sonographic over-/underestimation was determined relative to these. RESULTS:
      Enrolled prospectively into the study were 210 patients. The proportion of cases
      with sonographic underestimation, relative to final histology, of myometrial
      invasion (i.e. false-negative estimation of no or superficial invasion < 50%) and
      of cervical invasion (i.e. false-negative finding of absence of stromal invasion)
      was comparable: 8.6% (n = 18) and 10.5% (n = 22), respectively. Myometrial
      invasion was overestimated by ultrasound (i.e. false-positive estimation of deep
      invasion >= 50%) in 15.7% (n = 33) of cases, and cervical invasion was
      overestimated (i.e. false-positive finding of presence of stromal invasion) in
      4.8% (n = 10) of cases. These outcomes correspond to positive and negative
      predictive values of 67.6% (95% CI, 57.7-76.6) and 83.3% (95% CI, 74.9-89.8),
      respectively, for the subjective assessment of myometrial invasion, and 60.0%
      (95% CI, 38.2-79.2) and 88.1% (95% CI, 82.5-92.4), respectively, for that of
      cervical stromal invasion. The staging error in subjective assessment was not
      related to body mass index (BMI), to the position of the uterus in the pelvis or
      to image quality. Cervical and myometrial invasion were more often underestimated
      in well-differentiated endometrial cancers that were smaller in size, with thick
      minimum tumor-free myometrium and lower perfusion, and more often overestimated
      in moderately and poorly differentiated cancers that were larger in size, with
      thin minimum tumor-free myometrium and richer perfusion. CONCLUSION: The accuracy
      of subjective assessment of myometrial and cervical invasion by ultrasound was
      significantly influenced by tumor size, density of tumor vascularization, tumor
      vessel architecture and histological grading, while it was not significantly
      affected by BMI, uterine position and image quality.

PMID- 24281995
TI  - [Treatment of acute colonic pseudo-obstruction (Ogilvie's Syndrome). Systematic
      review].
AB  - BACKGROUND: Ogilvie's syndrome is acute colonic dilatation without organic
      obstacle in a previously healthy colon. Surgery is the only treatment of cases
      complicated by necrosis or perforation. In contrast, treatment of uncomplicated
      forms is not unanimous, and is the subject of this literature review. AIMS:
      Determine the results of different therapeutic methods of uncomplicated forms of
      Ogilvie's syndrome in terms of efficiency of removal of colonic distension,
      recurrence, morbidity and mortality. Clarify their respective indications.
      METHODS: An electronic literature search in the "MEDLINE" database, supplemented
      by hand searching on the reference lists of articles, was conducted for the
      period between 1980 and 2012. RESULTS: Conservative treatment is effective in 53
      to 96% of cases with a risk of colonic perforation less than 2.5% and a mortality
      of 0 to 14% % (level of evidence 4, recommendation grade C). Neostigmine is
      effective in 64 to 91% of cases after a first dose, with a risk of recurrence of
      0 to 38%. It remains effective in 40 to 100% of cases after a second dose
      (evidence level 2, grade recommendation B). Endoscopic decompression is a safe
      and effective technique with a success rate of 61 to 100% at the first attempt ,
      a recurrence rate of 0 to 50%, a rate of colonic perforation less than 5% and a
      mortality less than 5% (level evidence 4, recommendation grade C). PEG may be
      recommended for the prevention of recurrence of the ACPO after successful
      treatment with neostigmine or endoscopic decompression (evidence level 2,
      recommendation grade B). The cecostomy is more effective and safer than
      conventional colostomy (level of evidence 4, recommendation grade C). The
      cecostomy is highly effective in colonic decompression but associated with a high
      mortality (level of evidence 4, recommendation grade C). CONCLUSION: Conservative
      treatment is recommended in first intention. In case of failure, neostigmine
      should be tried. If unsuccessful, the endoscopic decompression is proposed. The
      cecostomy is indicated as a last resort after failure of endoscopic
      decompression.

PMID- 24281996
TI  - Evolution and prognosis of bladder papillomatosis managed by endoscopic resection
      and endovesical BCG therapy : about 24 cases.
AB  - BACKGROUND: Bladder papillomatosis is a diffuse tumor proliferation even up
      almost all of the bladder mucosa. We analyzed prognosis of this rare entity after
      conservative treatment. METHODS: We retrospectively analyzed epidemiological,
      clinical, therapeutic and evolutive data in 24 patients with newly diagnosed
      bladder transitional cell carcinoma papillomatosis. All patients underwent a
      complete endoscopic transurethral resection (TUR) with curative intent. A second
      look was performed within 30 days. The intravesical therapy regimen consisted on
      weekly instillations for 6 weeks, and then monthly for 6 months. If the tumor
      recurred without muscle invasion, TUR was repeated with a second intravesical
      BCGtherapy regimen. Parameters investigated included age, gender, risk factors,
      cystoscopic findings (aspect, multiplicity and location of bladder lesion), tumor
      stage, tumor grade, recurrences and progression times from diagnosis to last
      follow up. RESULTS: The mean age of the patients at initial diagnosis was 64,9+/
      6,1 years. They were males in 23 cases. Initial cancer staging was as follow: pTa
      (n=6) and pT1 (n=18). The recurring tumors were reported in 17 patients (70,8%).
      They were stage Ta in 5 patients and stage T1 in 12. The median interval of time
      between the initial TUR and the first recurrence was 10,3 months. Six patients
      remain tumor free. From the 17 recurrences, 6 patients developed progression with
      muscle invasion in 4 of them. Radical cystectomy with ileal conduit was performed
      in 3 patients and one patient died before radical treatment. Univariate analysis
      didn't reveal any prognostic factor: age (p=0,7), tumor location and aspect (p=
      0,7 and p= 0,5 respectively), tumor stage (p=0,7) and grade (p=0,09). CONCLUSION:
      TCC bladder papillomatosis is a rare entity. TUR with intravesical BCG therapy
      may be indicated as a first option despite correct follow up. Radical cystectomy
      should be considered in cases of recurrent or non-resectable tumours.

PMID- 24281997
TI  - [Iron status in pregnant women and its changes during preeclampsia].
AB  - BACKGROUND: Micronutrients or trace elements are minerals essential for growth
      and development of the body human. AIMS: To analyze changes in normal pregnancy
      and during preeclampsia, serum iron and its main proteins: ferritin and soluble
      transferrin receptors. METHODS: This is a prospective study of case- control
      study of 56 pregnant women and 30 non-pregnant women selected as controls.
      Pregnant women received a quarterly dosing parametres. The same assays were
      performed once in controls. RESULTS: The comparative assay of various parameters
      in normal pregnancy and in control women showed a significant decrease in serum
      iron from 1 to the third quarter, a slight decline in reserves ferritin in 1st
      and 2nd quarter increases and becomes significant in the third quarter and an
      increase of soluble receptors trasferrine during pregnancy, which becomes
      significant in the third quarter. We noted a disturbance of these parameters in
      preeclampsia. CONCLUSION: Iron is essential for fetal development. His
      involvement in several maternal- fetal complications is not to dismantle .

PMID- 24281998
TI  - [A descriptive study of the procedures of psychiatric admissions at Razi
      hospital].
AB  - BACKGROUND: The law 92-83, has established the rights of the mentally ill to
      respect for individual freedom and to appropriate care. However some gaps in its
      implementation led to the revision by Act 2004-40. AIM: To study the evolution of
      the number of admissions with and without consent (hospitalizations at the
      request of a third party and compulsory hospitalizations), between 2000 and 2009.
      METHODS: Retrospective study of the archives of the mental health unit of Razi
      hospital. The study population included inpatients under the mode of voluntary
      and involuntary admission either compulsory hospitalizations or at the request of
      a third party. RESULTS: An increase in the number of hospitalizations without the
      consent from 2000 to 2009 was noted. The number of compulsory hospitalizations
      and the one of hospitalizations at the request of a third party rose respectively
      from 1,048 to 1,443 and from 22 to 1,323. So the number of free hospitalizations
      has decreased while the number of involuntary hospitalizations has increased,
      leading to a constant number of total hospitalizations. The sex ratio for
      compulsory hospitalizations has increased from 2.04 to 5.83 while it markedly
      decreased for hospitalizations at the request of a third party (from 10 to
      1.7).Men, unlike women, were more likely to be hospitalized compulsorily than at
      the request of a third party. CONCLUSION: There is a larger use of hospital
      admissions under constraints than free ones; is it due to a concern for the
      respect of law or an abuse in the deprivation of freedom for some patients?

PMID- 24281999
TI  - [The value of multimodal imaging by single photon emission computed tomography
      associated to X ray computed tomography (SPECT-CT) in the management of
      differentiated thyroid carcinoma: about 156 cases].
AB  - BACKGROUND: Single photon emission computed tomography combined with a low dose
      computed tomography (SPECT-CT), is a hybrid imaging integrating functional and
      anatomical data. The purpose of our study was to evaluate the contribution of the
      SPECTCT over traditional planar imaging of patients with differentiated thyroid
      carcinoma (DTC). METHODS: Post therapy 131IWhole body scan followed by SPECTCT of
      the neck and thorax, were performed in 156 patients with DTC. RESULTS: Among
      these 156 patients followed for a predominantly papillary, the use of fusion
      imaging SPECT-CT compared to conventional planar imaging allowed us to correct
      our therapeutic approach in 26.9 % (42/156 patients), according to the protocols
      of therapeutic management of our institute. CONCLUSION: SPECT-CT is a multimodal
      imaging providing better identification and more accurate anatomic localization
      of the foci of radioiodine uptake with impact on therapeutic management.

PMID- 24282000
TI  - [In hospital mortality of ST segment elevation myocardial infarction treated with
      primary angioplasty: monocentric Tunisian study of 250 patients].
AB  - BACKGROUND: Myocardial reperfusion is the " corner stone " in the treatment of
      myocardial infarction. Primary percutaneous coronary intervention has proved its
      superiority upon intravenous thrombolysis. aim: To evaluate in hospital mortality
      of acute myocardial infarction treated with primary angioplasty and to determine
      its predictive factors. METHODS: We performed a retrospective study including 250
      patients admitted to Mongi Slim university Hospital at la Marsa between January
      the 1st, 2006 and June the 30th, 2011. All these patients had an ST segment
      elevation myocardial infarction and underwent primary percutaneous coronary
      intervention within 24 hours after symptom onset. RESULTS: In our study, males
      were predominant with a sex-ratio of 4.55. Our patients were aged 59.8+/- 11.19
      years old. Diabetes mellitus was present in 42% of our population. In 60.4% of
      the cases, myocardial infarction was located in the anterior wall. Cardiogenic
      shock was present in 13.6% of patients. The culprit coronary artery was the left
      anterior descending artery in 57.6% of the cases. The coronary flow in the
      culprit artery was TIMI 0 in 64% of the patients and TIMI 1 in 13.2% of the
      patients. Angiographic success (TIMI 3 flow and residual stenosis <20%) was
      achieved in 84% of cases. Our in-hospital mortality rate (cardiogenic shock
      excluded) was 6.9%. Predictive factors of in-hospital mortality were: female
      gender, diabetes mellitus, hypertension, renal failure, multi-vessel lesion,TIMI
      flow before percutaneous coronary intervention, proximal left anterior descending
      artery lesion, initial cardiogenic shock and acute stent thrombosis. CONCLUSION:
      In our local context, primary percutaneous coronary intervention is an efficient
      and safe treatment of myocardial infarction with persistent ST-segment elevation.

PMID- 24282001
TI  - [Assessment of nutritional status in patients with primary lung cancer].
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality
      worldwide. Malnutrition is a common problem among patients with cancer, affecting
      up to 85% of patients with certain cancers and represents a risk factor for poor
      prognosis. aim: evaluate nutritional status in patients with lung cancer before
      and during treatment using nutritional risk index. METHODS: it's a prospective
      study conducted in pneumology IV department in Abderahman Mami hospital, from
      January to May 2011. 30 male patients with a lung cancer were included.
      Nutritional status was assessed before and during treatment based on
      anthropometric measures, biological markers and nutritional risk index (NRI).
      RESULTS: Mean age of patients was 58 +/- 12 years, ranging from 19 to 82 years.
      29 patients had non small cell lung cancer and one patient had small cell cancer.
      Malnutrition was noted in 14 patients (47%) before treatment according to the
      NRI. It was noted in 23 patients (77%) after three cycles of chemotherapy with
      severe malnutrition in 8 patients. Relationship between body mass index (BMI) and
      the NRI was linear, but NRI tends to evaluate more objectively risk of
      malnutrition in patients with lung cancer. CONCLUSION: Nutritional assessment in
      patient with lung cancer should be performed systematically, early and
      repeatedly. Several markers can be used such as BMI and NRI. Nutritional support
      will reduce morbidity and improve quality of life in patients with lung cancer.

PMID- 24282003
TI  - [Long term outcomes of sleeve gastrectomy for morbid obesity].
AB  - BACKGROUND: Sleeve gastrectomy (SG) is a recent increasingly realized isolated
      procedure performed in the surgical treatment of obesity. AIM: The goal of this
      study was to evaluate the long term postoperative results among a multicentric
      cohort. METHODS: Retrospective multicenter study including patients operated from
      2006 to 2010 within the Brest's Bariatric Surgery Network. RESULTS: The immediate
      postoperative course was uneventful in 90%. The minor complication rate was 6.9%.
      The major complication rate was 3%. Postoperative mortality was nil. Late
      complication rate was 5%. The excess weight loss mean was 42 +/- 20 % at 4 years.
      Success rate was 55%, and the result was judged moderate in 31%. The improvement
      of co-morbidities has focused on type 2 diabetes to cure 49%, dyslipidemia was
      corrected in 60% of cases. Improved hypertension in 47% of cases, the
      disappearance of sleep apnea paired in 62% of cases. CONCLUSION: This study
      confirms in a multicenter feasibility of the SG and its effectiveness Long-term
      weight loss and resolution of comorbidities in addition it emphasizes the need
      for monitoring post operative extended to detect any vitamin deficiencies.

PMID- 24282004
TI  - [Colo-colonic intussusception owing to lipoma of transverse colon].

PMID- 24282005
TI  - [Malignant tumor of Brenner: one case report].

PMID- 24282006
TI  - [Renal AA amyloidosis during Langerhans' cell histiocytosis: case report].

PMID- 24282007
TI  - Computed tomography demonstration of an incarcerated lumbur hernia.

PMID- 24282008
TI  - [Epithelioid Angiomyolipoma mimicking renal carcinoma].

PMID- 24282009
TI  - [Traumatic uterine arteriovenous fistula: report of one case].

PMID- 24282010
TI  - Colouterine fistula complicating diverticulitis.

PMID- 24282011
TI  - [Geant ovary cyst].

PMID- 24282012
TI  - Gastric Xanthelasma: an uncommon lesion.

PMID- 24282013
TI  - [Genital tuberculosis simulating gynecologic cancer: about three cases].

PMID- 24282014
TI  - [Cardiac tamponade as an initial manifestation of systemic lupus erythematosus].

PMID- 24282015
TI  - [Pseudotumor pancreatic tuberculosis].

PMID- 24282016
TI  - [Colo-vesical fistula due to diverticulitis].

PMID- 24282017
TI  - Melanosis coli: an unusual cause of exudative enteropathy.

PMID- 24282018
TI  - Patient-centered blood management.
AB  - BACKGROUND: Transfusions are common in hospitalized patients but carry
      significant risk, with associated morbidity and mortality that increases with
      each unit of blood received. Clinical trials consistently support a conservative
      over a liberal approach to transfusion. Yet there remains wide variation in
      practice, and more than half of red cell transfusions may be inappropriate.
      Adopting a more comprehensive approach to the bleeding, coagulopathic, or anemic
      patient has the potential to improve patient care. METHODS: We present a patient
      centered blood management (PBM) paradigm. The 4 guiding principles of effective
      PBM that we present include anemia management, coagulation optimization, blood
      conservation, and patient-centered decision making. RESULTS: PBM has the
      potential to decrease transfusion rates, decrease practice variation, and improve
      patient outcomes. CONCLUSION: PBM's value proposition is highly aligned with that
      of hospital medicine. Hospitalists' dual role as front-line care providers and
      quality improvement leaders make them the ideal candidates to develop, implement,
      and practice PBM.

PMID- 24282020
TI  - Injuries in elite and recreational snowboarders.
AB  - BACKGROUND: The relatively young sport of snowboarding exhibits high injury
      rates. The current efforts to characterise the injury pattern of snowboarders
      focus largely on the general snowboard population and upper extremity injuries,
      the most common injury site in snowboarders as a whole. METHODS: In an effort to
      describe the current published information available on snowboarding injuries in
      the elite-level population, a literature search was performed and the articles
      related to snowboarding injuries were analysed. Additionally, the literature
      pertaining to biomechanical analyses of injury and injury prevention was
      included. RESULTS: Studies rarely stratify the snowboarders by skill level, a
      classification which has a profound effect on the riding activities of
      snowboarders and the resultant injury patterns. Elite-level snowboarders are
      often injured when performing difficult manoeuvres at high velocities and with
      amplified levels of force to the lower limbs. Consequently, elite-level
      snowboarders suffer from injuries that are of higher severity and have decidedly
      greater lower extremity injury rates. Conversely, injuries to the upper
      extremities are decreased in the elite snowboarders. Furthermore, little has been
      published regarding the biomechanical analyses and injury prevention for the
      protection of the lower extremities in snowboarding. CONCLUSIONS: Snowboarding
      continues to evolve as a sport. This includes a steady progression in the degree
      of difficulty of the manoeuvres conducted by athletes and an increase in the
      number of snowboarders attempting such manoeuvres. The injury patterns across the
      skill levels are markedly different, and it is imperative that the research
      directed towards understanding the disparate lower extremity injury pattern of
      elite-level snowboarders is increased.

PMID- 24282019
TI  - Efficacy and tolerability of chemotherapy with modified dose-dense TCF regimen
      (TCF-dd) in locally advanced or metastatic gastric cancer: final results of a
      phase II trial.
AB  - BACKGROUND: We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating
      its feasibility and an activity comparable to epirubicin-based chemotherapy and
      TCF q3w in terms of overall survival and time to progression (TTP). We report
      here the final results of a phase II study of chemotherapy with a modified TCF-dd
      regimen in locally advanced or metastatic gastric cancer (MGC). METHODS AND STUDY
      DESIGN: Patients with histologically confirmed measurable MGC, not previously
      treated for advanced disease, received docetaxel 70 mg/m(2) day 1, cisplatin 60
      mg/m(2) day 1, l-folinic acid 100 mg/m(2) days 1 and 2, followed by 5
      fluorouracil (5-FU) 400 mg/m(2) bolus days 1 and 2, and then 600 mg/m(2) as a 22
      h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day
      3. Patients aged >=65 years received the same schedule with a dose reduction of
      30 %. RESULTS: Study duration: December 2007-November 2010. Forty-six consecutive
      patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38
      76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate
      (ORR). A median of four cycles (range, one to six) was administered. Forty-three
      patients were evaluated for response (93.5 %) and all for toxicity: 3 complete
      response (CR), 25 partial response (PR), 10 stable disease (SD), and 5
      progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of
      61 % (95 % CI 47-75). Median overall survival (OS) was 17.63 months (95 % CI,
      13.67-20.67); median progression-free survival was 8.9 months (95 % CI, 6.5
      13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay,
      thus respecting the dose-dense criterion. Most frequent grade 3-4 toxicities were
      neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %),
      febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11
      %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe. CONCLUSIONS: The
      TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very
      active and needs to be further tested in randomized studies.

PMID- 24282021
TI  - Dissection of the octoploid strawberry genome by deep sequencing of the genomes
      of Fragaria species.
AB  - Cultivated strawberry (Fragaria x ananassa) is octoploid and shows allogamous
      behaviour. The present study aims at dissecting this octoploid genome through
      comparison with its wild relatives, F. iinumae, F. nipponica, F. nubicola, and F.
      orientalis by de novo whole-genome sequencing on an Illumina and Roche 454
      platforms. The total length of the assembled Illumina genome sequences obtained
      was 698 Mb for F. x ananassa, and ~200 Mb each for the four wild species.
      Subsequently, a virtual reference genome termed FANhybrid_r1.2 was constructed by
      integrating the sequences of the four homoeologous subgenomes of F. x ananassa,
      from which heterozygous regions in the Roche 454 and Illumina genome sequences
      were eliminated. The total length of FANhybrid_r1.2 thus created was 173.2 Mb
      with the N50 length of 5137 bp. The Illumina-assembled genome sequences of F. x
      ananassa and the four wild species were then mapped onto the reference genome,
      along with the previously published F. vesca genome sequence to establish the
      subgenomic structure of F. x ananassa. The strategy adopted in this study has
      turned out to be successful in dissecting the genome of octoploid F. x ananassa
      and appears promising when applied to the analysis of other polyploid plant
      species. 

PMID- 24282022
TI  - Stability of monoclonal antibodies at high-concentration: head-to-head comparison
      of the IgG1 and IgG4 subclass.
AB  - Few studies have so far directly compared the impact of antibody subclass on
      protein stability. This case study investigates two mAbs (one IgG1 and one IgG4 )
      with identical variable region. Investigations of mAbs that recognize similar
      epitopes are necessary to identify possible differences between the IgG
      subclasses. Both physical and chemical stability were evaluated by applying a
      range of methods to measure formation of protein aggregates [size-exclusion
      chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism
      and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal
      interactions (dynamic light scattering), and fragmentation and deamidation (SEC
      HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic
      strength (10 and 150 mM) was investigated using highly-concentrated (150 mg/mL)
      mAb formulations. Lower conformational stability was identified for the IgG4
      resulting in increased levels of soluble aggregates. The IgG1 was chemically less
      stable as compared with the IgG4 , presumably because of the higher flexibility
      in the IgG1 hinge region. The thermodynamic stability of individual mAb domains
      was also addressed in detail. The stability of our mAb molecules is clearly
      affected by the IgG framework, and this study suggests that subclass switching
      may alter aggregation propensity and aggregation pathway and thus potentially
      improve the overall formulation stability while retaining antigen specificity.

PMID- 24282023
TI  - BASHD-J-resolved-HMBC, an efficient method for measuring proton-proton and
      heteronuclear long-range coupling constants.
AB  - Natural products often possess various spin systems consisting of a methine group
      directly bonded to a methyl group (e.g. -CHa-CHb(CH3)-CHc-). The methine proton
      Hb splits into a broadened multiplet by coupling with several vicinal protons,
      rendering analysis difficult of (n)JC-H with respect to Hb in the J-resolved HMBC
      1. In purpose of the reliable and easy measurements of (n)JC-H and (n)JH-H in the
      aforesaid spin system, we have developed a new technique, named BASHD-J-resolved
      HMBC. This method incorporates band selective homo decoupled pulse and J-scaling
      pulse into HMBC. In this method, high resolution cross peaks can be observed
      along the F1 axis by J-scaling pulse, and band selective homo decoupled pulse
      simplified multiplet signals. Determinations of (n)JC-H and (n)JH-H of multiplet
      signals can easily be performed using the proposed pulse sequence.

PMID- 24282024
TI  - Following solid-acid-catalyzed reactions by MAS NMR spectroscopy in liquid phase-
      zeolite-catalyzed conversion of cyclohexanol in water.
AB  - A microautoclave magic angle spinning NMR rotor is developed enabling in situ
      monitoring of solid-liquid-gas reactions at high temperatures and pressures. It
      is used in a kinetic and mechanistic study of the reactions of cyclohexanol on
      zeolite HBEA in 130  degrees C water. The (13) C spectra show that dehydration of
      1-(13) C-cyclohexanol occurs with significant migration of the hydroxy group in
      cyclohexanol and the double bond in cyclohexene with respect to the (13) C label.
      A simplified kinetic model shows the E1-type elimination fully accounts for the
      initial rates of 1-(13) C-cyclohexanol disappearance and the appearance of the
      differently labeled products, thus suggesting that the cyclohexyl cation
      undergoes a 1,2-hydride shift competitive with rehydration and deprotonation.
      Concurrent with the dehydration, trace amounts of dicyclohexyl ether are
      observed, and in approaching equilibrium, a secondary product, cyclohexyl-1
      cyclohexene is formed. Compared to phosphoric acid, HBEA is shown to be a more
      active catalyst exhibiting a dehydration rate that is 100-fold faster per proton.

PMID- 24282025
TI  - Solution properties of gamma-crystallins: hydration of fish and mammal gamma
      crystallins.
AB  - Lens gamma crystallins are found at the highest protein concentration of any
      tissue, ranging from 300 mg/mL in some mammals to over 1000 mg/mL in fish. Such
      high concentrations are necessary for the refraction of light, but impose extreme
      requirements for protein stability and solubility. gamma-crystallins, small
      stable monomeric proteins, are particularly associated with the lowest hydration
      regions of the lens. Here, we examine the solvation of selected gamma-crystallins
      from mammals (human gammaD and mouse gammaS) and fish (zebrafish gammaM2b and
      gammaM7). The thermodynamic water binding coefficient B1 could be probed by
      sucrose expulsion, and the hydrodynamic hydration shell of tightly bound water
      was probed by translational diffusion and structure-based hydrodynamic boundary
      element modeling. While the amount of tightly bound water of human gammaD was
      consistent with that of average proteins, the water binding of mouse gammaS was
      found to be relatively low. gammaM2b and gammaM7 crystallins were found to
      exhibit extremely low degrees hydration, consistent with their role in the fish
      lens. gammaM crystallins have a very high methionine content, in some species up
      to 15%. Structure-based modeling of hydration in gammaM7 crystallin suggests low
      hydration is associated with the large number of surface methionine residues,
      likely in adaptation to the extremely high concentration and low hydration
      environment in fish lenses. Overall, the degree of hydration appears to balance
      stability and tissue density requirements required to produce and maintain the
      optical properties of the lens in different vertebrate species.

PMID- 24282026
TI  - Oct-2 transcription factor binding activity and expression up-regulation in rat
      cerebral ischaemia is associated with a diminution of neuronal damage in vitro.
AB  - Brain plasticity provides a mechanism to compensate for lesions produced as a
      result of stroke. The present study aims to identify new transcription factors
      (TFs) following focal cerebral ischaemia in rat as potential therapeutic targets.
      A transient focal cerebral ischaemia model was used for TF-binding activity and
      TF-TF interaction profile analysis. A permanent focal cerebral ischaemia model
      was used for the transcript gene analysis and for the protein study. The
      identification of TF variants, mRNA analysis, and protein study was performed
      using conventional polymerase chain reaction (PCR), qPCR, and Western blot and
      immunofluorescence, respectively. Rat cortical neurons were transfected with
      small interfering RNA against the TF in order to study its role. The TF-binding
      analysis revealed a differential binding activity of the octamer family in
      ischaemic brain in comparison with the control brain samples both in acute and
      late phases. In this study, we focused on Oct-2 TF. Five of the six putative Oct
      2 transcript variants are expressed in both control and ischaemic rat brain,
      showing a significant increase in the late phase of ischaemia. Oct-2 protein
      showed neuronal localisation both in control and ischaemic rat brain cortical
      slices. Functional studies revealed that Oct-2 interacts with TFs involved in
      important brain processes (neuronal and vascular development) and basic cellular
      functions and that Oct-2 knockdown promotes neuronal injury. The present study
      shows that Oct-2 expression and binding activity increase in the late phase of
      cerebral ischaemia and finds Oct-2 to be involved in reducing ischaemic-mediated
      neuronal injury. 

PMID- 24282028
TI  - Metabotropic glutamate receptor 5 knockout promotes motor and biochemical
      alterations in a mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder
      caused by a polyglutamine expansion in the amino-terminal region of the
      huntingtin protein, which promotes progressive neuronal cell loss, neurological
      symptoms and death. In the present study, we show that blockade of mGluR5 with
      MTEP promotes increased locomotor activity in both control (Hdh(Q20/Q20)) and
      mutant HD (Hdh(Q111/Q111)) mice. Although acute injection of MTEP increases
      locomotor activity in both control and mutant HD mice, locomotor activity is
      increased in only control mice, not mutant HD mice, following the genetic
      deletion of mGluR5. Interestingly, treatment of mGluR5 knockout mice with either
      D1 or D2 dopamine antagonists eliminates the increased locomotor activity of
      mGluR5 knockout mice. Amphetamine treatment increases locomotor activity in
      control mice, but not mGluR5 null mutant HD mice. However, the loss of mGluR5
      expression improves rotarod performance and decreases the number of huntingtin
      intranuclear inclusions in mutant HD mice. These adaptations may be due to mutant
      huntingtin-dependent alterations in gene expression, as microarray studies have
      identified several genes that are altered in mutant, but not wild-type HD mice
      lacking mGluR5 expression. qPCR experiments confirm that the mRNA transcript
      levels of dynein heavy chain, dynactin 3 and dynein light chain-6 are altered
      following the genetic deletion of mGluR5 in mutant HD mice, as compared with wild
      type mutant HD mice. Thus, our data suggest that mutant huntingtin protein and
      mGluR5 exhibit a functional interaction that may be important for HD-mediated
      alterations in locomotor behavior and the development of intranuclear inclusions.

PMID- 24282027
TI  - Functional interaction of Parkinson's disease-associated LRRK2 with members of
      the dynamin GTPase superfamily.
AB  - Mutations in LRRK2 cause autosomal dominant Parkinson's disease (PD). LRRK2
      encodes a multi-domain protein containing GTPase and kinase domains, and putative
      protein-protein interaction domains. Familial PD mutations alter the GTPase and
      kinase activity of LRRK2 in vitro. LRRK2 is suggested to regulate a number of
      cellular pathways although the underlying mechanisms are poorly understood. To
      explore such mechanisms, it has proved informative to identify LRRK2-interacting
      proteins, some of which serve as LRRK2 kinase substrates. Here, we identify
      common interactions of LRRK2 with members of the dynamin GTPase superfamily.
      LRRK2 interacts with dynamin 1-3 that mediate membrane scission in clathrin
      mediated endocytosis and with dynamin-related proteins that mediate mitochondrial
      fission (Drp1) and fusion (mitofusins and OPA1). LRRK2 partially co-localizes
      with endosomal dynamin-1 or with mitofusins and OPA1 at mitochondrial membranes.
      The subcellular distribution and oligomeric complexes of dynamin GTPases are not
      altered by modulating LRRK2 in mouse brain, whereas mature OPA1 levels are
      reduced in G2019S PD brains. LRRK2 enhances mitofusin-1 GTP binding, whereas
      dynamin-1 and OPA1 serve as modest substrates of LRRK2-mediated phosphorylation
      in vitro. While dynamin GTPase orthologs are not required for LRRK2-induced
      toxicity in yeast, LRRK2 functionally interacts with dynamin-1 and mitofusin-1 in
      cultured neurons. LRRK2 attenuates neurite shortening induced by dynamin-1 by
      reducing its levels, whereas LRRK2 rescues impaired neurite outgrowth induced by
      mitofusin-1 potentially by reversing excessive mitochondrial fusion. Our study
      elucidates novel functional interactions of LRRK2 with dynamin-superfamily
      GTPases that implicate LRRK2 in the regulation of membrane dynamics important for
      endocytosis and mitochondrial morphology. 

PMID- 24282030
TI  - A genome-wide association study identifies polymorphisms in the HLA-DR region
      associated with non-response to hepatitis B vaccination in Chinese Han
      populations.
AB  - Vaccination against hepatitis B virus is an effective and routine practice that
      can prevent infection. However, 5-10% of healthy adults fail to produce
      protective levels of antibody against the hepatitis B vaccination. It has been
      reported that host genetic variants might affect the immune response to hepatitis
      B vaccination. Here, we reported a genome-wide association study in a Chinese Han
      population consisting of 108 primary high-responders and 77 booster non
      responders to hepatitis B vaccination using the Illumina HumanOmniExpress
      Beadchip. We identified 21 SNPs at 6p21.32 were significantly associated with non
      response to booster hepatitis B vaccination (P-value <1 * 10(-6)). The most
      significant SNP in the region was rs477515, located ~12 kb upstream of the HLA
      DRB1 gene. Its P-value (4.81 * 10(-8)) exceeded the Bonferroni-corrected genome
      wide significance threshold. Four tagging SNPs (rs477515, rs28366298, rs3763316
      and rs13204672) that capture genetic information of these 21 SNPs were validated
      in three additional Chinese Han populations, consisting of 1336 primary high
      responders and 420 primary non-responders. The four SNPs continued to show
      significant associations with non-response to hepatitis B vaccination (P-combined
      = 3.98 * 10(-13)- 1.42 * 10(-8)). Further analysis showed that the rs477515 was
      independently associated with non-response to hepatitis B vaccination with
      correction for other three SNPs in our GWAS and the known hepatitis B vaccine
      immunity associated SNP in previous GWAS. Our findings suggest that the rs477515
      was an independent marker associated with non-response to hepatitis B vaccination
      and HLA-DR region might be a critical susceptibility locus of hepatitis B vaccine
      induced immunity. 

PMID- 24282031
TI  - Altered regulation of DNA ligase IV activity by aberrant promoter DNA methylation
      and gene amplification in colorectal cancer.
AB  - Colorectal cancer (CRC) presents as a very heterogeneous disease which cannot
      sufficiently be characterized with the currently known genetic and epigenetic
      markers. To identify new markers for CRC we scrutinized the methylation status of
      231 DNA repair-related genes by methyl-CpG immunoprecipitation followed by global
      methylation profiling on a CpG island microarray, as altered expression of these
      genes could drive genomic and chromosomal instability observed in these tumors.
      We show for the first time hypermethylation of MMP9, DNMT3A and LIG4 in CRC which
      was confirmed in two CRC patient groups with different ethnicity. DNA ligase IV
      (LIG4) showed strong differential promoter methylation (up to 60%) which
      coincided with downregulation of mRNA in 51% of cases. This functional
      association of LIG4 methylation and gene expression was supported by LIG4 re
      expression in 5-aza-2'-deoxycytidine-treated colon cancer cell lines, and reduced
      ligase IV amounts and end-joining activity in extracts of tumors with
      hypermethylation. Methylation of LIG4 was not associated with other genetic and
      epigenetic markers of CRC in our study. As LIG4 is located on chromosome 13 which
      is frequently amplified in CRC, two loci were tested for gene amplification in a
      subset of 47 cases. Comparison of amplification, methylation and expression data
      revealed that, in 30% of samples, the LIG4 gene was amplified and methylated, but
      expression was not changed. In conclusion, hypermethylation of the LIG4 promoter
      is a new mechanism to control ligase IV expression. It may represent a new
      epigenetic marker for CRC independent of known markers. 

PMID- 24282032
TI  - Prevalence and predictors of suicidal behavior among Mongolian high school
      students.
AB  - The purpose of this study was to examine the prevalence and predictors of
      suicidal behavior among Mongolian high school students. Females were more likely
      to have suicidal behavior than males. No close friends, feelings of loneliness,
      insomnia, self perception of underweight or overweight, carrying a weapon were
      significant predictors of students' suicidal behavior. Missing school without
      permission, being bullied and going hungry were also important risk factors of
      suicidal ideation. Families and Schools are important environments to prevent
      high students' suicide. Improving students' psychological well being, quality of
      relationship with people, and support resources are critical to prevent suicidal
      behavior. 

PMID- 24282033
TI  - Lifetime trauma and suicide attempts in people with severe mental illness.
AB  - We examined associations among six forms of common lifetime traumatic/adverse
      events and lifetime suicide attempts while controlling for gender, psychiatric
      symptoms, self-injury, and substance use in 371 community mental health clients
      with severe mental illness. Most clients (88.1%) reported at least one traumatic
      event, and more than half had attempted suicide at least once. Regression
      revealed that three factors were significantly associated with lifetime suicide
      attempts: lifetime self-injurious behaviors, lifetime physical abuse, and alcohol
      use. Having been physically abused appears to be uniquely associated with
      lifetime suicide attempts when other key risk factors are controlled. Limitations
      include the cross-sectional design.

PMID- 24282034
TI  - Pharmacological treatment for psychotic depression.
AB  - BACKGROUND: Evidence is limited regarding the most effective pharmacological
      treatment for psychotic depression: combination of an antidepressant plus an
      antipsychotic, monotherapy with an antidepressant or monotherapy with an
      antipsychotic. This is an update of a review first published in 2005 and last
      updated in 2009. OBJECTIVES: 1. To compare the clinical efficacy of
      pharmacological treatments for patients with an acute psychotic depression:
      antidepressant monotherapy, antipsychotic monotherapy and the combination of an
      antidepressant plus an antipsychotic, compared with each other and/or with
      placebo.2. To assess whether differences in response to treatment in the current
      episode are related to non-response to prior treatment. SEARCH METHODS: A search
      of the Cochrane Central Register of Controlled Trials and the Cochrane
      Depression, Anxiety and Neurosis Group Register (CCDANCTR) was carried out (to 12
      April 2013). These registers include reports of randomised controlled trials from
      the following bibliographic databases: EMBASE (1970-), MEDLINE (1950-) and
      PsycINFO (1960-). Reference lists of all studies and related reviews were
      screened and key authors contacted. SELECTION CRITERIA: All randomised controlled
      trials (RCTs) that included participants with acute major depression with
      psychotic features, as well as RCTs consisting of participants with acute major
      depression with or without psychotic features, that reported separately on the
      subgroup of participants with psychotic features. DATA COLLECTION AND ANALYSIS:
      Two review authors independently extracted data and assessed risk of bias in the
      included studies, according to the criteria of the Cochrane Handbook for
      Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used
      intention-to-treat data. For dichotomous efficacy outcomes, the risk ratio (RR)
      with 95% confidence intervals (CIs) was calculated. For continuously distributed
      outcomes, it was not possible to extract data from the RCTs. Regarding the
      primary outcome of harm, only overall dropout rates were available for all
      studies. MAIN RESULTS: The search identified 3659 abstracts, but only 12 RCTs
      with a total of 929 participants could be included in the review. Because of
      clinical heterogeneity, few meta-analyses were possible. The main outcome was
      reduction of severity (response) of depression, not of psychosis.We found no
      evidence for the efficacy of monotherapy with an antidepressant or an
      antipsychotic.However, evidence suggests that the combination of an
      antidepressant plus an antipsychotic is more effective than antidepressant
      monotherapy (three RCTs; RR 1.49, 95% CI 1.12 to 1.98, P = 0.006), more effective
      than antipsychotic monotherapy (four RCTs; RR 1.83, 95% CI 1.40 to 2.38, P =
      0.00001) and more effective than placebo (two identical RCTs; RR 1.86, 95% CI
      1.23 to 2.82, P = 0.003).Risk of bias is considerable: there were differences
      between studies with regard to diagnosis, uncertainties around randomisation and
      allocation concealment, differences in treatment interventions (pharmacological
      differences between the various antidepressants and antipsychotics) and different
      outcome criteria. AUTHORS' CONCLUSIONS: Psychotic depression is heavily
      understudied, limiting confidence in the conclusions drawn. Some evidence
      indicates that combination therapy with an antidepressant plus an antipsychotic
      is more effective than either treatment alone or placebo. Evidence is limited for
      treatment with an antidepressant alone or with an antipsychotic alone.

PMID- 24282035
TI  - Self-perception of cognitive function among patients with active acromegaly,
      controlled acromegaly, and non-functional pituitary adenoma: a pilot study.
AB  - Pituitary adenomas (PAs) represent 15 % of all brain tumors. One-sixth of these
      are reported to cause acromegaly via excess growth hormone secretion. These
      tumors have been associated with multiple comorbidities, including
      neuropsychiatric and cognitive dysfunction. We aimed to assess patient perception
      of cognitive deficits and the relationship of cognitive changes to active
      acromegaly (AA) versus controlled acromegaly (CA) versus non-functional PAs
      (NFPA). A modified FACT-Cog survey was used, which focused on the prevalence and
      severity of perceived dysfunction in five areas of cognitive function: ability to
      learn, concentration/distractibility, mental agility, memory and recall, and
      verbal recall. Patient perception of current health and health change over the
      previous 12 months was also assessed. The overall perceived prevalence and
      severity of cognitive dysfunction were the highest among NFPA groups,
      particularly in the areas of mental agility, verbal recall, and memory/recall.
      Patients with AA reported greater prevalence and severity of dysfunction with
      respect to concentration/distractibility and ability to learn. Patients with AA
      reported the best overall current health, though patients with CA reported the
      greatest improvement in health over the previous year. These findings may
      indicate that PAs can affect cognitive function regardless of whether excess
      growth hormone is present. Acromegaly and NFPA patients perceive specific areas
      of cognitive dysfunction that may require further evaluation and treatment.
      Further research may be useful regarding patient quality of life, patient
      functionality during normal daily activities, and perceived dysfunction despite
      biological disease control.

PMID- 24282037
TI  - Harmful effects of functional hypercortisolism: a working hypothesis.
AB  - Functional hypercortisolism (FH) is caused by conditions able to chronically
      activate hypothalamic-pituitary-adrenal axis and usually occurs in cases of major
      depression, anorexia nervosa, bulimia nervosa, alcoholism, diabetes mellitus,
      simple obesity, polycystic ovary syndrome, obstructive sleep apnea syndrome,
      panic disorder, generalized anxiety disorder, shift work, and end-stage renal
      disease. Most of these states belong to pseudo-Cushing disease, a condition which
      is difficult to distinguish from Cushing's syndrome and characterized not only by
      biochemical findings but also by objective ones that can be attributed to
      hypercortisolism (e.g., striae rubrae, central obesity, skin atrophy, easy
      bruising, etc.). This hormonal imbalance, although reversible and generally mild,
      could mediate some systemic complications, mainly but not only of a
      metabolic/cardiovascular nature, which are present in these states and are
      largely the same as those present in Cushing's syndrome. In this review we aim to
      discuss the evidence suggesting the emerging negative role for FH. 

PMID- 24282036
TI  - Prediction of gestational diabetes mellitus in the first trimester, comparison of
      fasting plasma glucose, two-step and one-step methods: a prospective randomized
      controlled trial.
AB  - Our aim was to evaluate and compare the diagnostic performance of three methods
      commonly used for GDM screening: fasting plasma glucose (FPG), two-step 50 g
      glucose challenge test (GCT), and 75 g glucose tolerance test (GTT) in a
      randomized study design to predict GDM in the first trimester and determine the
      best approach in predicting GDM. In a non-blind, parallel-group prospective
      randomized controlled study; 736 singleton pregnant women underwent FPG testing
      in the first trimester and randomly assigned to two groups; two-step 50 g GCT and
      75 g GTT. GDM diagnosis was made according to Carpenter-Coustan or ADA (American
      Diabetes Association) criteria in two-step 50 g GCT and 75 g GTT groups,
      respectively. Subsequent testing was performed by two-step 50 g GCT at 24-28
      weeks for screen negatives. After excluding the women who were lost to follow-up
      or withdrawn as a result of pregnancy loss, 486 pregnant women were recruited in
      the study. The FPG, two-step GCT, and one-step GTT methods identified GDM in
      25/486 (5.1 %), 15/248 (6.0 %), and 27/238 (11.3 %) women, respectively. Area
      under ROC curves were 0.623, 0.708, and 0.792, respectively. Sensitivities were
      47.17, 68.18, and 87.1 %, respectively. Specificities were 77.37, 100, and 100 %,
      respectively. Positive predictive values were 20.33, 100, and 100 %,
      respectively. Negative predictive values were 92.29, 97, and 98.1 %,
      respectively. Until superior screening alternatives become available, the 75 g
      GTT may be preferred for GDM screening in the first trimester.

PMID- 24282029
TI  - Quantifying rare, deleterious variation in 12 human cytochrome P450 drug
      metabolism genes in a large-scale exome dataset.
AB  - The study of genetic influences on drug response and efficacy
      ('pharmacogenetics') has existed for over 50 years. Yet, we still lack a complete
      picture of how genetic variation, both common and rare, affects each individual's
      responses to medications. Exome sequencing is a promising alternative method for
      pharmacogenetic discovery as it provides information on both common and rare
      variation in large numbers of individuals. Using exome data from 2203 AA and 4300
      Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a
      survey of coding variation within 12 Cytochrome P450 (CYP) genes that are
      collectively responsible for catalyzing nearly 75% of all known Phase I drug
      oxidation reactions. In addition to identifying many polymorphisms with known
      pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles
      across the 12 CYP genes of interest. These alleles include many with diverse
      functional effects such as premature stop codons, aberrant splicesites and
      mutations at conserved active site residues. Our analysis considering both novel,
      predicted functional alleles as well as known, actionable CYP alleles reveals
      that rare, deleterious variation contributes markedly to the overall burden of
      pharmacogenetic alleles within the populations considered, and that the
      contribution of rare variation to this burden is over three times greater in AA
      individuals as compared with Caucasians. While most of these impactful alleles
      are individually rare, 7.6-11.7% of individuals interrogated in the study carry
      at least one newly described potentially deleterious alleles in a major drug
      metabolizing CYP. 

PMID- 24282038
TI  - Cardiovascular events in acromegaly: distinct role of Agatston and Framingham
      score in the 5-year prediction.
AB  - Prediction of ischemic cardiovascular events (ICE) in acromegalic patients
      stratified accordingly with Framingham (FS) and Agatston score (AS). 32 patients
      with active (group A (0)) and 20 with controlled (group B (0)) acromegaly have
      been enrolled. During the 5-year follow-up, 19 out of 32 patients in group A (0)
      reached disease control. At entry, FS and AS, by an eight-slice MDCT scanner,
      were calculated in all patients. ICE were diagnosed by autopsy, if lethal, and by
      electrocardiography and/or echocardiography, if non-lethal. Overall, 9.6 % of
      patients died for lethal ICE. AS >400, but not high FS at entry, was associated
      with increased risk of lethal ICE. Lethal ICE had occurred in two patients of
      group A (0) and three of group B (0) (p NS), while a non-lethal ICE had occurred
      in two cases of the former and in other two of the latter group (p NS). Either FS
      or AS was correlated with the risk for ICE overall (p < 0.02), but only AS
      correlated with that of lethal ICE (p < 0.0003). Survival analysis demonstrated
      reduced life expectancy in patients with high FS (p < 0.02). In acromegalics, AS
      >400 is associated with increased risk of lethal ICE, while high FS is associated
      with reduced life expectancy, regardless of disease control.

PMID- 24282039
TI  - Unexpected conversion from hypothyroidism to an euthyroid state due to Graves'
      disease in a patient with an ectopic thyroid.
AB  - A 15-year-old woman was diagnosed with hypothyroidism and unilateral ectopic
      thyroid. Levothyroxine treatment was introduced; however, the patient was non
      compliant and took the medication irregularly. When she presented to an
      endocrinologist at the age of 30, she had not been using levothyroxine for at
      least 6 months. Surprisingly, she was clinically and biochemically euthyroid. Due
      to decreased echogenicity on ultrasound examination, enhanced vascularization on
      Color Doppler examination and increased concentration of anti-TSH receptor
      autoantibodies, she was diagnosed with Graves' disease. Eventually, she underwent
      total thyroidectomy due to diagnosis of follicular neoplasm in fine-needle
      aspiration biopsy of the focal lesion found in the thyroid gland. To our
      knowledge, our patient is the first described with ectopic thyroid, presenting a
      nodular variant of Graves' disease and no signs of orbitopathy, who was initially
      hypothyroid and became euthyroid in the course of autoimmune thyroid disease. 

PMID- 24282040
TI  - NHS arm's length bodies and regulatory networks in England: quantitative
      analysis.
AB  - Health regulation is an area of English public policy that involves a plethora of
      different bodies operating independently of one another with the purported aim of
      monitoring standards, ensuring minimum standards are met and providing assurance
      for the public and government. The purpose of this research is to ascertain as
      well as possible whether regulation generally is having a positive effect on
      service provision as well as what the relationship between the data collected by
      these bodies is. The rationale for testing whether the effect of regulation is
      positive is obvious; it costs money, time and effort, so does it work? The
      rationale for testing the relationships is that providers who score well on
      quality measures should also be experiencing fewer deaths compared with what
      would be expected. They should also be the providers who are performing well in
      terms of finances and governance. If there is no relationship between these data
      sets, then surely something is going wrong; that is, does the various regulatory
      monitoring and scrutiny actually measure what it sets out to measure?

PMID- 24282042
TI  - Association of hospitalist presence and hospital-level outcome measures among
      Medicare patients.
AB  - BACKGROUND: Hospitalists have been shown to lower patient costs through better
      resource utilization and decreased length of stay, but it is unclear whether
      hospitalists are associated with quality of care. We examined the association
      between the presence of hospitalists and 30-day predicted excess all-cause
      hospital mortality and readmissions among Medicare patients admitted to a
      hospital with any of 3 conditions: heart failure, acute myocardial infarction,
      and pneumonia. METHODS: Using national hospital-level, case mix-adjusted, risk
      standardized, 30-day all-cause excess mortality and readmission data from the
      Centers for Medicare and Medicaid Services, we used descriptive and bivariate
      statistics to illustrate trends across hospitals. Using multivariable ordinary
      least squares regression to control for hospital-level characteristics, we then
      estimated the association between the presence of hospitalists and predicted
      hospital mortality and readmission. RESULTS: After multivariable adjustment, the
      presence of hospitalists was associated with lower probability of readmission for
      all 3 target conditions. No significant associations for any of the target
      conditions were found in all-cause mortality models. CONCLUSIONS: Hospitalists
      are already integral to the delivery of inpatient care at most institutions. This
      study, however, showed an association at the national level of the presence of
      hospitalists with an important and timely quality measure: reduction of
      readmission rates. Future research is indicated to explore specific causation
      pathways for the impact of hospitalists on quality of care.

PMID- 24282041
TI  - Hip strength: ankle proprioceptive threshold ratio predicts falls and injury in
      diabetic neuropathy.
AB  - INTRODUCTION: We determined lower limb neuromuscular capacities associated with
      falls and fall-related injuries in older people with declining peripheral nerve
      function. METHODS: Thirty-two subjects (67.4 +/- 13.4 years; 19 with type 2
      diabetes), representing a spectrum of peripheral neurologic function, were
      evaluated with frontal plane proprioceptive thresholds at the ankle, frontal
      plane motor function at the ankle and hip, and prospective follow-up for 1 year.
      RESULTS: Falls and fall-related injuries were reported by 20 (62.5%) and 14
      (43.8%) subjects, respectively. The ratio of hip adductor rate of torque
      development to ankle proprioceptive threshold (Hip(STR) /AnkPRO ) predicted falls
      (pseudo-R(2)  = .726) and injury (pseudo-R(2)  = .382). No other variable
      maintained significance in the presence of Hip(STR) /AnkPRO . CONCLUSIONS: Fall
      and injury risk in the population studied is related inversely to Hip(STR)
      /AnkPRO . Increasing rapidly available hip strength in patients with neuropathic
      ankle sensory impairment may decrease risk of falls and related injuries.

PMID- 24282043
TI  - Computer system to support medication reviews: a good but not new concept.

PMID- 24282044
TI  - A fully automated medication review?

PMID- 24282045
TI  - Tumor-targeted redox-responsive nonviral gene delivery nanocarriers based on
      neutral-cationic brush block copolymers.
AB  - Novel neutral-cationic brush block copolymer, poly[oligo(ethylene glycol)
      monomethyl ether methacrylate-co-folic acid methacrylate]-b-poly[2-(2-(2-(2-bromo
      2-methylpropanoyloxy)-ethyl) disulfanyl) ethyl methacrylate-g-2
      dimethylaminoethyl methacrylate], P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA), is
      synthesized via consecutive controlled radical polymerizations. Containing
      disulfide linkages bridging backbone and side chains in the cationic brush block
      and cancer cell-targeting ligands (folic acid) in the neutral hydrophilic block,
      the diblock copolymer is employed as a tumor-targeted redox-responsive degradable
      nonviral gene delivery vector. P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA) brush block
      copolymers can condense plasmid DNA (pDNA) efficiently via the formation of
      electrostatic polyplex micelles. Under reductive milieu, pDNA can be released due
      to the cleavage of disulfide linkages and accordingly pDNA-binding cationic
      PDMAEMA side chains. In addition, the brush block copolymer exhibits low
      cytotoxicity and the corresponding polyplex micelles show relatively high gene
      transfection efficiency. 

PMID- 24282046
TI  - Studies on the MxiH protein in T3SS needles using DNP-enhanced ssNMR
      spectroscopy.
AB  - Bacterial T3SS needles formed by the protein MxiH are studied using DNP-enhanced
      ssNMR spectroscopy at 14.1 T (600 MHz). This technique provides spectra of good
      resolution, allowing us to draw conclusions about the protein dynamics. With the
      obtained signal enhancement, samples of limited quantity now get within reach of
      ssNMR studies. 

PMID- 24282047
TI  - Detection of acute pulmonary embolism: feasibility of diagnostic accuracy of MRI
      using a stepwise protocol.
AB  - Multidetector computed tomography (MDCT) has become the imaging method of choice
      in patients suspected of having pulmonary embolism (PE) but has the inherent
      limitation of radiation dose and the side effects of contrast agents. The purpose
      of the study was to assess the feasibility of a stepwise MRI protocol in the
      clinical setting of acute PE. The stepwise approach should make it possible to
      diagnose acute PE in critically ill patients using fast MR sequences and included
      the option to add comprehensive sequences when patients were stable. Forty-five
      patients with acute PE (26 men, 19 women; 41 +/- 16 years) were included in this
      prospective study. The diagnosis was initially confirmed by MDCT as gold
      standard. MRI at 1.5 T was subsequently performed without any delay in medical
      treatment. The MRI protocol proceeded stepwise from robust to detailed imaging
      techniques (i.e., from TrueFISP and single shot HASTE sequence to MR perfusion
      and 3D-MR angiography) if the patient was able to tolerate additional imaging
      time. Diagnostic accuracy was evaluated on the central (lobar) and peripheral
      (segmental) levels. The complete MR protocol was applied in 40 of the 45 patients
      (88 %). In the remaining five patients with severe dyspnea the diagnosis of acute
      PE was established by using fast TrueFISP sequences that were insensitive to
      respiratory movement. All five patients suffered from a major central PE. Highest
      sensitivity was achieved by MR perfusion (lobar, 98 %; segmental, 95 %). Real
      time TrueFISP and MR angiography showed the highest specificity (lobar, 90-100 %;
      segmental, 95-97 %). The combination of all MR sequences matched closely the
      results of MDCT (lobar: sensitivity 98 %, specificity 100 %; segmental:
      sensitivity 95 %, specificity 97 %). MRI using a stepwise protocol is a promising
      approach for diagnosing acute PE. The protocol can be tailored for dyspneic
      patients with central PE using real-time MRI sequences. The diagnostic accuracy
      for peripheral PE can be improved by using combined MR techniques, achieving
      comparable results to MDCT.

PMID- 24282048
TI  - Nondestructive analysis of structure and components of tablet coated with film by
      the usage of terahertz time-domain reflection spectroscopy.
AB  - Nondestructive analysis of tablet is of great importance from the aspect of
      productivity and safety. In terahertz (THz) region, however, the analysis of core
      of coated tablet has not been progressed. In this study, we have measured a flat
      surface push-pull osmotic pump tablet, having no orifice, having bilayer core and
      a coating film layer. The bilayer core was made from the drug layer and the push
      layer, and acetaminophen was contained in the drug layer as a model drug. To
      study its structure and components, we have obtained reflection spectra from the
      drug layer side and the push layer side measurements using THz time-domain
      reflection spectroscopy (THz-TDRS). From these results, detection of the peak of
      acetaminophen in the spectrum from the drug layer side measurements was
      confirmed. We have made ridges approximated toward the peak using a general
      method of linear regression analysis in both spectra. Two-sample t-test was
      applied to their gradients, and significant difference between the drug layer and
      the push layer was shown. These results suggested that THz-TDRS is applicable to
      the analysis of structure and component of a coated tablet.

PMID- 24282049
TI  - Telemedicine and toxicology: back to the future?

PMID- 24282050
TI  - White-light-emitting supramolecular gels.
AB  - Let there be light, let it be white: Recent developments in the use of
      chromophore-based gels as scaffolds for the assembly of white-light-emitting soft
      materials have been significant. The main advantage of this approach lies in the
      facile accommodation of selected luminescent components within the gel.
      Excitation-energy-transfer processes between these components ultimately generate
      the desired light output. 

PMID- 24282051
TI  - Colonic mucosal immune activity in irritable bowel syndrome: comparison with
      healthy controls and patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: Mucosal immune activity may participate in irritable bowel
      syndrome (IBS) pathogenesis. Mast- and T cell numbers from patients with IBS or
      ulcerative colitis (UC) and healthy controls were determined. METHODS: Between
      November 2007 and May 2012, patients with diarrhea-predominant IBS (D-IBS, n =
      83), 49 patients with UC, and 25 healthy controls were recruited. Of the UC
      group, 28 were in remission and 21 had mildly active UC. Biopsies from each colon
      segment were subjected to immunohistochemical analysis. The mast cells,
      intraepithelial lymphocytes (IELs), and lamina proprial lymphocytes (LPLs) were
      counted. RESULTS: Compared to the healthy controls, the patients with D-IBS, UC
      in remission, and mildly active UC had significantly higher mean colorectal
      mucosal mast-cell, IEL, and LPL counts. Comparison with the colon segments
      (ascending, transverse, descending, and sigmoid segments) that had once been
      involved in UC (in the patients with remission) revealed that the D-IBS colons
      had similar immune-cell counts. However, they had significantly fewer immune
      cells than the colon segments that presently showed involvement in the patients
      with mildly-activated UC. The mast-cell and IEL counts were similar in the D-IBS
      rectums and once-involved UC rectums but significantly higher in the presently
      involved UC rectums. However, both the once-involved and presently-involved UC
      rectums had significantly higher LPL counts than the D-IBS rectums. CONCLUSIONS:
      Patients with D-IBS had significantly higher colonic mucosal immune-cell counts
      than healthy controls but had similar counts to patients with UC in remission.
      The symptoms in both conditions may originate from low-grade inflammation in the
      colonic mucosa.

PMID- 24282052
TI  - Hydrogen peroxide-assisted endoscopic necrosectomy for walled-off pancreatic
      necrosis: a dual center pilot experience.

PMID- 24282053
TI  - Etiology and adverse outcome predictors of upper gastrointestinal bleeding in 589
      patients in Nepal.
AB  - BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common clinical condition
      associated with significant morbidity and mortality. AIM: The purpose of this
      study was to determine the etiology of UGIB and predict the adverse outcome of
      variceal and non-variceal UGIB by using the parameters of validated scores.
      METHODS: This is a prospective observational study in which 589 UGIB patients
      underwent upper gastrointestinal endoscopy from May 2010 to April 2013 in Nepal.
      The variables of Glasgow-Blatchford score (GBS) and Rockall score (RS) were used
      to predict adverse outcomes, which were defined as transfusion, rebleeding,
      readmission, surgery and death within 30 days. RESULTS: Among UGIB patients, 33.1
      % were variceal and 66.9 % were non-variceal bleeding (peptic ulcers 23.9 %,
      gastric erosion 16.5 % and others). The adverse outcomes of variceal and non
      variceal UGIB were 77.9 % and 72.6 %, respectively. The significant predictors of
      adverse outcome were hemoglobin and systolic blood pressure in overall UGIB (p <
      0.001), blood urea (p = 0.002), melena (p < 0.001) and syncope (p < 0.001) in
      variceal UGIB, and heart rate, melena, syncope and malignancy in non-variceal
      UGIB (p < 0.001). The area under receiver operating curve for adverse outcome in
      overall UGIB was 0.76, 0.80 and 0.94 using clinical RS, complete RS and GBS,
      respectively (p < 0.001). CONCLUSIONS: Variceal bleeding was the leading cause of
      UGIB in Nepal followed by peptic ulcers and gastric erosion. Those variables of
      GBS and RS, which were significant predictors of adverse outcome for UGIB, can be
      utilized in determining more aggressive endoscopic management during endoscopy,
      or more prolonged intravenous proton pump inhibitor use, or an additional day or
      two of hospitalization.

PMID- 24282054
TI  - Primary surgical resection versus liver transplantation for transplant-eligible
      hepatocellular carcinoma patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of mortality
      worldwide. Existing studies comparing outcomes after liver transplantation (LT)
      versus surgical resection among transplant-eligible patients are conflicting.
      AIM: The purpose of this study was to compare long-term survival between
      consecutive transplant-eligible HCC patients treated with resection versus LT.
      METHODS: The present retrospective matched case cohort study compares long-term
      survival outcomes between consecutive transplant-eligible HCC patients treated
      with resection versus LT using intention-to-treat (ITT) and as-treated models.
      Resection patients were matched to LT patients by age, sex, and etiology of HCC
      in a 1:2 ratio. RESULTS: The study included 171 patients (57 resection and 114
      LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs.
      12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre
      model for end stage liver disease (MELD) era, LT patients had significantly
      better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04),
      but no difference was seen in the ITT model. In the multivariate Cox proportional
      hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre
      MELD vs. post-MELD), treatment with resection was an independent predictor of
      poorer survival (HR 2.72; 95 % CI, 1.08-6.86). CONCLUSION: Transplant-eligible
      HCC patients who received LT had significantly better survival than those treated
      with resection, suggesting that patients who can successfully remain on LT
      listing and actually undergo LT have better outcomes.

PMID- 24282055
TI  - Clinical presentation and survival of Asian and non-Asian patients with HCV
      related hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV) is an important cause of
      hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to
      the high prevalence of hepatitis B virus in Asians. This study examines HCV
      related HCC in Asians. METHODS: We conducted a retrospective cohort study of 792
      consecutive Asian (n = 220) and non-Asian (n = 572) patients with HCV-related HCC
      identified at Stanford University Medical Center using International
      Classification of Diseases-9 diagnosis between July 1996 and June 2012. RESULTS:
      Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P < 0.0001] and
      more likely to be female (33 vs. 19 %, P < 0.0001). A larger proportion of Asians
      were diagnosed with HCC within 2 years of HCV diagnosis (35 vs. 20 %, P = 0.001).
      Asian patients were more likely to undergo palliative therapy (46 vs. 28 %) and
      less likely to be listed for liver transplantation (20 vs. 48 %, P < 0.001),
      despite similar rates of meeting Milan criteria (52 vs. 58 %, P = 0.16). Overall,
      there was a trend for higher median survival rates in Asians (30 vs. 21 months, P
      = 0.091). Asians had higher long-term survival with palliative therapy only (5
      year survival: 28 vs. 10 %, P < 0.0001); however, survival was similar among
      patients listed for liver transplantation. CONCLUSIONS: There were distinct
      differences in clinical presentations of Asian and non-Asian patients with HCV
      related HCC. Asians with HCV-related HCC are less likely to undergo liver
      transplantation and more likely to have delayed HCV diagnosis. Improved
      strategies in HCV screening in Asians are needed, as it may lead to earlier
      diagnosis and treatment of HCV infection and possible prevention of HCC
      development.

PMID- 24282056
TI  - On the question of ethnicity and its impact on IBD-related outcomes.

PMID- 24282057
TI  - Association of TM4SF4 with the human thiamine transporter-2 in intestinal
      epithelial cells.
AB  - BACKGROUND: The human thiamine transporter-2 (hTHTR-2) is involved in the
      intestinal absorption of thiamine. Recent studies with membrane transporters of
      other nutrients/substrates have shown that they have associated proteins that
      affect different aspects of their physiology and cell biology. Nothing is known
      about protein(s) that interact with hTHTR-2 in intestinal epithelial cells and
      influence its physiological function and/or its cell biology. AIMS: The aim of
      this study was to identify protein partner(s) that interact with hTHTR-2 in human
      intestinal cells and determine the physiological/biological consequence of that
      interaction. METHODS: The yeast split-ubiquitin two-hybrid approach was used to
      screen a human intestinal cDNA library. GST-pull-down and cellular co
      localization approaches were used to confirm the interaction between hTHTR-2 and
      the associated protein(s). The effect of such an interaction on hTHTR-2 function
      was examined by (3)H-thiamine uptake assays. RESULTS: Our screening results
      identified the human TransMembrane 4 SuperFamily 4 (TM4SF4) as a potential
      interactor with hTHTR-2. This interaction was confirmed by an in vitro GST-pull
      down assay, and by live-cell confocal imaging of HuTu-80 cells co-expressing
      hTHTR-2-GFP and mCherry-TM4SF4 (the latter displayed a significant overlap of
      these two proteins in intracellular vesicles and at the cell membrane). Co
      expression of hTHTR-2 with TM4SF4 in HuTu-80 cells led to a significant induction
      in thiamine uptake. In contrast, silencing TM4SF4 with gene-specific siRNA led to
      a significant decrease in thiamine uptake. CONCLUSIONS: These results show for
      the first time that the accessory protein TM4SF4 interacts with hTHTR-2 and
      influences the physiological function of the thiamine transporter.

PMID- 24282058
TI  - Conflicting results on the efficacy of enteral nutrition during infliximab
      maintenance therapy for Crohn's disease are correct.

PMID- 24282059
TI  - Different gastric mucosa and CagA status of patients in India and Japan infected
      with Helicobacter pylori.
AB  - BACKGROUND AND AIM: Despite similar incidence of Helicobacter pylori infection,
      the frequency of gastric cancer is sevenfold higher in Japan than in India. The
      objective of this work was to define differences in H. pylori-induced gastritis
      and to identify the bacterial virulence factors involved. MATERIALS AND METHODS:
      We prospectively enrolled 353 consecutive patients who underwent endoscopy and
      received three gastric biopsies in Tokyo, Japan, and Hyderabad, India.
      Immunohistochemistry against H. pylori and East Asian CagA and hematoxylin-eosin
      and Giemsa stain were used to examine gastric mucosal biopsy specimens.
      Histological scores were assessed in accordance with the updated Sydney System.
      Subjects with H. pylori infection were matched by age and sex to compare
      histopathology and bacterial virulence. RESULTS: Sixty patients infected with H.
      pylori were prospectively selected. Median histological scores for neutrophil and
      mononuclear cell infiltration and for atrophy were significantly higher in Japan
      than in India (neutrophils 4.0 vs 3.0, p < 0.01; mononuclear cells 5.0 vs 4.5, p
      = 0.03; atrophy 3.0 vs 2.0, p < 0.01, respectively). Scores for H. pylori density
      and intestinal metaplasia were also higher in Japan, albeit without statistical
      significance (H. pylori 5.0 vs 3.0, p = 0.08; intestinal metaplasia 0.0 vs 0.0, p
      = 0.08). Prevalence of East Asian CagA-positive H. pylori was significantly
      higher in Japan (73.3 vs 0.0 %, p < 0.01). CONCLUSION: The significantly higher
      prevalence of histologically severe gastritis and East Asian CagA in patients
      from Japan with H. pylori infection may be involved in the pathogenesis of
      gastric cancer.

PMID- 24282060
TI  - Transcriptome profiling identifies differentially expressed genes in postnatal
      developing pituitary gland of miniature pig.
AB  - In recent years, Tibetan pig and Bama pig are popularly used as animal models for
      medical researches. However, little genomic information is available for the two
      breeds, particularly regarding gene expression pattern at the whole-transcriptome
      level. In this study, we characterized the pituitary transcriptome profile along
      their postnatal developmental stages within and between the two breeds in order
      to illustrate the differential dynamics and functions of differentially expressed
      genes. We obtained a total of ~300 million 80-bp paired-end reads, detected 15
      715 previously annotated genes. Most of the genes (90.33%) were shared between
      the two breeds with the main functions in metabolic process. Four hormone genes
      (GH, PRL, LHB, and FSHB) were detected in all samples with extremely high levels
      of expression. Functional differences between the three developmental stages
      (infancy, puberty and adulthood) in each breed were dominantly presented by the
      gene expressions at the first stage. That is, Bama pig was over-represented in
      the genes involved in the cellular process, while Tibetan pig was over
      represented in the genes represented by the reproductive process. The identified
      SNPs indicated that the divergence between the miniature pig breeds and the large
      pig (Duroc) were greater than that between the two miniature pig breeds. This
      study substantially expands our knowledge concerning the genes transcribed in the
      pig pituitary gland and provides an overview of pituitary transcriptome dynamics
      throughout the period of postnatal development. 

PMID- 24282061
TI  - Oligoprogenitor cells derived from spermatogonia stem cells improve remyelination
      in demyelination model.
AB  - Embryonic stem (ES) like cells-derived testis represents a possible alternative
      to replace of neurons and glia. Here, we differentiated spermatogonia cells to
      oligoprogenitor (OP) like cells and transplanted them to demyelination model and
      assess their recovery potential in a demyelinated corpus callosum model in rats.
      ES like cells were differentiated to OP like cells using appropriate inducers and
      were transplanted in situ to demyelinated corpus callosum. Cell integration as
      well as demyelination extension and myelination intensity changes were evaluated
      using histologic studies and immunocytochemistry after 2 and 4 weeks post
      transplantation. Investigation of Nestin, NF68, Olig2, and NG2 by
      immunocytochemical technique indicated the differentiation of ES like cells to
      neuroprogenitor and oligodendrocyte like cells in each induction stage.
      Histologic findings showed a significant decrease in demyelination extension and
      a significant increase in remyelination intensity in cell transplanted groups.
      Also on the base of PLP expression, differentiation of transplanted cells was
      confirmed to myelinogenic cells using immunocytochemistry technique. We conclude
      that ES like cells derived from spermatogonia cells can be differentiated to OP
      like cells that can form myelin after transplantation into the demyelination
      model in rat, this represents recovery potential of spermatogonia cells which
      opens new window for cell therapeutic approaches using spermatogonial stem cells.

PMID- 24282063
TI  - Acetaldehyde and the genome: beyond nuclear DNA adducts and carcinogenesis.
AB  - The designation of acetaldehyde associated with the consumption of alcoholic
      beverages as "carcinogenic to humans" (Group 1) by the International Agency for
      Research on Cancer (IARC) has brought renewed attention to the biological effects
      of acetaldehyde, as the primary oxidative metabolite of alcohol. Therefore, the
      overall focus of this review is on acetaldehyde and its direct and indirect
      effects on the nuclear and mitochondrial genome. We first consider different
      acetaldehyde-DNA adducts, including a critical assessment of the evidence
      supporting a role for acetaldehyde-DNA adducts in alcohol related carcinogenesis,
      and consideration of additional data needed to make a conclusion. We also review
      recent data on the role of the Fanconi anemia DNA repair pathway in protecting
      against acetaldehyde genotoxicity and carcinogenicity, as well as teratogenicity.
      We also review evidence from the older literature that acetaldehyde may impact
      the genome indirectly, via the formation of adducts with proteins that are
      themselves critically involved in the maintenance of genetic and epigenetic
      stability. Finally, we note the lack of information regarding acetaldehyde
      effects on the mitochondrial genome, which is notable since aldehyde
      dehydrogenase 2 (ALDH2), the primary acetaldehyde metabolic enzyme, is located in
      the mitochondrion, and roughly 30% of East Asian individuals are deficient in
      ALDH2 activity due to a genetic variant in the ALDH2 gene. In summary, a
      comprehensive understanding of all of the mechanisms by which acetaldehyde
      impacts the function of the genome has implications not only for alcohol and
      cancer, but types of alcohol related pathologies as well.

PMID- 24282062
TI  - Nutritional interventions for reducing gastrointestinal toxicity in adults
      undergoing radical pelvic radiotherapy.
AB  - BACKGROUND: Across the developed world, an estimated 150,000 to 300,000 people
      are treated annually with pelvic radiotherapy and 80% will develop
      gastrointestinal (GI) symptoms during treatment. Acute GI symptoms are associated
      with a greater risk of chronic, often debilitating, GI symptoms. Up to one-third
      of patients are malnourished before pelvic radiotherapy and up to four-fifths of
      patients lose weight during treatment. Malnutrition is linked to a higher risk of
      GI toxicity, which can lead to breaks in radiotherapy and early cessation of
      chemotherapy, thus compromising the efficacy of the primary cancer treatment.
      OBJECTIVES: To assess the effects of nutritional interventions for reducing GI
      toxicity in adults undergoing radical pelvic radiotherapy. SEARCH METHODS: We
      searched the Cochrane Gynaecological Cancer Group's Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), Issue 4, 2012, MEDLINE and
      EMBASE to May 2012. We handsearched the citation lists of included studies and
      previous systematic reviews identified to identify further relevant trials.
      SELECTION CRITERIA: We included studies if they were randomised controlled trials
      (RCTs) or non-randomised studies with concurrent comparison groups including
      quasi-randomised trials, cluster RCTs, non-randomised trials, prospective and
      retrospective cohort studies, and case series of 30 or more patients. We only
      included studies if they assessed the effect of a nutritional intervention in
      adults aged 18 years or over undergoing radical pelvic radiotherapy as part of
      anticancer treatment for a primary pelvic malignancy. We excluded patients with
      stomas and a previous history of inflammatory bowel disease. Nutritional support
      interventions could be provided at any stage before or during pelvic radiotherapy
      and included dietary counselling; dietary modification of fibre, lactose or fat;
      supplementary foods or drinks or fortified foods; standard oral nutrition
      supplements including polymeric-, peptide- or amino acid-based supplements and
      those where novel substrates have been added; enteral tube feeds; or parenteral
      nutrition (partial or total). We excluded probiotics, prebiotics and synbiotics.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      quality and extracted data. We contacted study authors to obtain missing data. We
      assessed bias for each of the included studies using the bias assessment tables
      in the Cochrane software Review Manager5. We performed meta-analysis, when
      indicated, using the Mantel-Haenszel fixed-effect method or inverse variance
      fixed-effect method displayed with heterogeneity. We undertook meta-analyses on
      trials evaluating dietary modification against standard treatment for diarrhoea
      at the end of radiotherapy and for change in weight from baseline to end of
      radiotherapy. MAIN RESULTS: The searches identified 7558 titles, and we excluded
      7513 during title and abstract searches. We reviewed 45 papers in full, and
      excluded 39. We identified four studies on handsearching of the references,
      which, along with the six eligible papers from the database search, led to 10
      studies being included. Four studies, three of which were RCTs and one
      prospective study, investigated the effect of elemental diet on GI symptoms; one
      RCT investigated the effect of dietary modification and elemental diet; and five
      RCTs investigated dietary modification. Studies were varied in terms of risk of
      bias. Data were dichotomised for presence and absence of diarrhoea at the end of
      radiotherapy for four trials evaluating dietary modification comprising modified
      fat, lactose, fibre or combinations of these dietary changes. A reduction in
      diarrhoea was demonstrated with nutritional intervention (risk ratio (RR) 0.66;
      95% confidence interval (CI) 0.51 to 0.87, four studies, 413 participants,
      moderate quality of evidence) with low heterogeneity (Chi(2) = 3.50, I(2) = 14%).
      Two trials evaluating dietary modification on weight change (comparing baseline
      and end of radiotherapy) showed no difference between intervention or control
      (mean difference (MD) -0.57 kg; 95% CI -1.22 to 0.09) with low heterogeneity
      (Chi(2) = 1.41, I(2) = 29%). Generally adverse effects were poorly reported in
      included studies. Elemental diet in particular was poorly tolerated. GI symptoms
      or toxicity > 6 months after radiotherapy was not reported in included studies
      AUTHORS' CONCLUSIONS: There have been benefits demonstrated with dietary
      modification during pelvic radiotherapy to reduce diarrhoea. Those diets included
      single interventions or combinations of modified fat, lactose-restriction, fat
      restriction and fibre supplementation. We were unable to meta-analyse elemental
      diet, as data were not available. We considered some of the studies to be at high
      risk of bias. There have been recent advances in novel, more targeted
      radiotherapy techniques, such that the findings of older studies need to be
      interpreted with caution. In addition, there were problems with compliance and
      palatability with some of the interventions, particularly elemental diet, which
      limits its usefulness in clinical practice.

PMID- 24282064
TI  - RNA interference-mediated silencing of a Halloween gene spookier affects nymph
      performance in the small brown planthopper Laodelphax striatellus.
AB  - Post-embryonic development of insects is highly dependent on ecdysteroid hormone
      20-hydroxyecdysone. Halloween gene spookier (spok, cyp307a2) has been documented
      to be involved in ecdysteroidogenesis in Drosophila melanogaster and Bombyx mori.
      We describe here the cloning and characterization of Halloween gene spookier
      (Lsspok, Lscyp307a2) in the small brown planthopper Laodelphax striatellus, a
      hemipteran insect species. LsSPOK has three insect-conserved P450 motifs, that
      is, Helix-K, PERF motif and heme-binding domain. Temporal and spatial expression
      patterns of Lsspok were evaluated by quantitative polymerase chain reaction.
      Through the fouth-instar and the early fifth-instar stages, Lsspok showed two
      expression peaks in the second- and fifth-day fourth-instar nymphs, and two
      troughs in the first-day fourth and fifth instars. On day 5 of the fourth-instar
      nymphs, Lsspok clearly had a high transcript level in the thorax where
      prothoracic glands were located. Dietary introduction of double-stranded RNA of
      Lsspok in the nymph stage successfully knocked down the target gene, decreased
      expression level of ecdysone receptor (LsEcR) gene, caused nymphal lethality and
      delayed development. Ingestion of 20-hydroxyecdysone in Lsspok-dsRNA-exposed
      nymphs did not increase Lsspok expression level, but almost completely rescued
      the LsEcR mRNA level and relieved the negative effects on survival and
      development. Thus, our data suggest that the ecdysteroidogenic pathway is
      conserved in insects and LsSPOK is responsible for specific steps in
      ecdysteroidogenesis in L. striatellus. 

PMID- 24282065
TI  - Nanopressing: toward tailored polymer microstructures and nanostructures.
AB  - A simple and versatile method is developed for preparing anisotropic polymer
      particles by pressing polymer microspheres at elevated temperatures. Polystyrene
      (PS) microspheres are used to demonstrate this approach. Depending on the
      mechanical deformation and wetting of the polymers on the substrates, polymer
      structures with special shapes such as barrel-like or dumbbell-like shapes can be
      prepared. The morphology of polymer structures can be controlled by the
      experimental parameters such as the pressing pressure, the pressing temperature,
      and the pressing time. The wetting of the polymers on the substrates dominates
      when the samples are annealing at higher temperatures for longer times. 

PMID- 24282066
TI  - Comparison of kidney disease: improving global outcomes and acute kidney injury
      network criteria for assessing patients in intensive care units.
AB  - BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) group proposed
      to adopt the 48-h time window for the 0.3 mg/dL rise in serum creatinine (sCr)
      proposed by the Acute Kidney Injury Network (AKIN) group as a modification to the
      original risk, injury, failure, loss, and end-stage renal disease criteria,
      keeping the 7-day window for the 50 % increase in sCr from baseline. The present
      study evaluates the prevalence of acute kidney injury (AKI) and the accuracy of
      predicting mortality based on the KDIGO and AKIN criteria. PATIENTS AND METHODS:
      We retrospectively studied a cohort of 2579 patients admitted to the intensive
      care unit of Nagoya University Hospital between 2005 and 2009. RESULTS: The total
      AKI prevalence was higher according to the KDIGO than to the AKIN criteria (38.4
      versus 29.5 %). In-hospital mortality rates were higher among 238 patients
      classified as non-AKI by the AKIN but AKI by the KDIGO criteria than among those
      classified as non-AKI by both criteria (7.1 versus 2.7 %). Survival curves
      generated using KDIGO significantly differed among all stages, but not between
      AKIN stages I and II. Multivariate analysis showed that KDIGO criteria were
      better in a statistical model than the AKIN criteria according to the Akaike
      information criterion. Harrell's C statistic was greater for the KDIGO than for
      the AKIN criteria. CONCLUSIONS: The KDIGO criteria have improved sensitivity
      without compromising specificity for AKI and might predict mortality at least as
      well as the AKIN criteria.

PMID- 24282067
TI  - Antidromic sensory nerve conduction study of the digital branches of the medial
      plantar nerve: a novel method to detect early diabetic sensory axonal
      polyneuropathy.
AB  - INTRODUCTION: Distal sensory neuropathy is the most common form of diabetic
      neuropathy. We developed a novel antidromic technique for assessment of distal
      nerve function for early diagnosis of diabetic neuropathy. METHODS: Diabetic and
      control groups underwent standard and more distal sensory nerve conduction
      studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital
      branches of the medial plantar nerve were recorded with our method after
      stimulation at the sole and recording from digits I and II. RESULTS: Comparison
      between controls and diabetics showed a statistically significant difference in
      mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs
      was obtained with our technique than with either conventional or more distal NCS
      in all patients. CONCLUSIONS: As compared with clinical evaluation and other NCS,
      our antidromic stimulation was the most sensitive method to detect abnormal
      sensory nerve conduction in symptomatic and asymptomatic diabetic patients.

PMID- 24282068
TI  - Functional roles of the pepper MLO protein gene, CaMLO2, in abscisic acid
      signaling and drought sensitivity.
AB  - Plants are frequently exposed to various environmental stresses including drought
      in the natural environment and have evolved physiological, biochemical, and
      molecular mechanisms to counteract the deleterious effects of stress. Of them,
      modulation of abscisic acid (ABA) signal transduction allows plants to overcome
      stress. Recently, Kim and Hwang (Plant J 72:843-855, 2012) identified CaMLO2 that
      is transcriptionally induced by both biotic and abiotic stress. Based on this, we
      tested the possibility that CaMLO2 is involved in abiotic stress, although m
      ildew resistance l ocus O (MLO) proteins have been known as negative regulators
      in plant defense responses against powdery mildew. The CaMLO2 gene was strongly
      induced in pepper leaves exposed to ABA and drought. Virus-induced gene silencing
      of CaMLO2 in pepper plants showed low levels of transpiration and lipid
      peroxidation in dehydrated leaves. Overexpression of the CaMLO2 gene in
      Arabidopsis conferred reduced sensitivity to ABA in germination and seedling
      growth and establishment. High transpiration rates and low degrees of stomatal
      closure in response to ABA also led transgenic plants to be more vulnerable to
      drought than the wild-type, which was accompanied by altered expression of stress
      related genes. Taken together, these data suggest that CaMLO2 acts as a negative
      regulator of ABA signaling that suppresses water loss from leaves under drought
      conditions. 

PMID- 24282070
TI  - In vitro and in vivo safety evaluation of biodegradable self-assembled monomethyl
      poly (ethylene glycol)-poly (epsilon-caprolactone)-poly (trimethylene carbonate)
      micelles.
AB  - Safety evaluation of self-assembled polymeric micelles is important for
      biomedical involvement in drug delivery systems in the future. In this study,
      biodegradable monomethyl poly (ethylene glycol)-poly (epsilon-caprolactone)-poly
      (trimethylene carbonate) [MPEG-P(CL-co-TMC)] copolymer was synthesized and
      characterized by Fourier transform infrared spectroscopy, nuclear magnetic
      resonance analysis, and gel permeation chromatography. MPEG-P(CL-co-TMC) micelles
      were prepared by self-assembly without any organic solvent. The present study was
      conducted to assess the safety of blank MPEG-P(CL-co-TMC) micelles both in vitro
      and in vivo. Particle size (30.09 +/- 0.06 nm) and zeta potential (0.067 +/-
      0.027 mV) of obtained micelles were determined by Malvern laser particle size
      analyzer. The results of in vitro toxicity evaluation implied that the prepared
      micelles did not cause hemolysis or severely cell toxicity. Meanwhile, we did not
      observe any toxic response or histopathological changes in the study of in vivo
      acute toxicity evaluation and histopathological study of MPEG-P(CL-co-TMC)
      micelles. In conclusion, the maximal tolerance dose of MPEG-P(CL-co-TMC) micelles
      (100 mg/mL) by intravenous injection was supposed to be greater than 10 g/kg body
      weight. Therefore, it might have potential applications in biomedical field.

PMID- 24282069
TI  - Functions of the CCCH type zinc finger protein OsGZF1 in regulation of the seed
      storage protein GluB-1 from rice.
AB  - Glutelins are the most abundant storage proteins in rice grain and can make up to
      80 % of total protein content. The promoter region of GluB-1, one of the glutelin
      genes in rice, has been intensively used as a model to understand regulation of
      seed-storage protein accumulation. In this study, we describe a zinc finger gene
      of the Cys3His1 (CCCH or C3H) class, named OsGZF1, which was identified in a
      yeast one-hybrid screening using the core promoter region of GluB-1 as bait and
      cDNA expression libraries prepared from developing rice panicles and grains as
      prey. The OsGZF1 protein binds specifically to the bait sequence in yeast and
      this interaction was confirmed in vitro. OsGZF1 is predominantly expressed in a
      confined domain surrounding the scutellum of the developing embryo and is
      localised in the nucleus. Transient expression experiments demonstrated that
      OsGZF1 can down-regulate a GluB-1-GUS (beta-glucuronidase) reporter and OsGZF1
      was also able to significantly reduce activation conferred by RISBZ1 which is a
      known strong GluB-1 activator. Furthermore, down-regulation of OsGZF1 by an RNAi
      approach increased grain nitrogen concentration. We propose that OsGZF1 has a
      function in regulating the GluB-1 promoter and controls accumulation of glutelins
      during grain development. 

PMID- 24282071
TI  - Photostability of 4,4'-dihydroxythioindigo, a mimetic of indigo.
AB  - The photochemical properties of indigo, a widely used industrial dye, has
      attracted both experimentalists and theoreticians from the beginning. Especially
      the high photostability of indigo has been the subject of intensive research.
      Recently, it was proposed that after photoexcitation an intramolecular proton
      transfer followed by a nonradiative relaxation to the ground state promote
      photostability. In indigo the hydrogen bond and the proton transfer occur between
      the opposing hemiindigo parts. Here, we provide experimental and theoretical
      evidence that a hydrogen transfer within one hemiindigo or hemithioindigo part is
      sufficient to attain photostability. This concept can serve as an interesting
      strategy towards new photostable dyes for the visible part of the spectrum. 

PMID- 24282072
TI  - Ecotoxicological impact of MSW landfills: assessment of teratogenic effects by
      means of an adapted FETAX assay.
AB  - The introduction of chemical products into the environment can cause long-term
      effects on the ecosystems. Increasing efforts are being made to determine the
      extent of contamination in particularly affected areas using diverse methods to
      assess the ecotoxicological impact. We used a modified Frog Embrio Toxicity Assay
      Xenopus method to determine the extent of toxicological load in different sample
      soils obtained near three municipal solid waste landfills in Catalonia (Spain).
      The results show that the Garraf landfill facility produces more embryotoxic
      damage to the surroundings, than the others ones: Can Mata landfill and
      Montferrer-Castellbo landfill. The aim of this work is to demonstrate how
      different management of complex sources of contamination as the controlled
      dumping sites can modulate the presence of toxics in the environment and their
      effects and through this, help determine the safer way to treat these wastes. To
      this effect some conceptual modifications have been made on the established
      American Society for Testing and Materials protocol. The validity of the new
      model, both as to model of calculation as to protocol, has been demonstrated in
      three different sites with complex sources of contamination. 

PMID- 24282073
TI  - Topical cystic fibrosis transmembrane conductance regulator gene replacement for
      cystic fibrosis-related lung disease.
AB  - BACKGROUND: Cystic fibrosis is caused by a defective gene encoding a protein
      called the cystic fibrosis transmembrane conductance regulator (CFTR), and is
      characterised by chronic lung infection resulting in inflammation and progressive
      lung damage that results in a reduced life expectancy. OBJECTIVES: To determine
      whether topical CFTR gene replacement therapy to the lungs in people with cystic
      fibrosis is associated with improvements in clinical outcomes, and to assess any
      adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group Trials Register comprising references identified from
      comprehensive electronic database searches, handsearching relevant journals and
      abstract books of conference proceedings.Date of most recent search: 22 August
      2013.An additional search of the National Institutes for Health (NIH) Genetic
      Modification Clinical Research Information System (GeMCRIS) was also performed
      for the years 1992 to 2013.Date of most recent search: 04 September 2013.
      SELECTION CRITERIA: Randomised controlled trials comparing topical CFTR gene
      delivery to the lung, using either viral or non-viral delivery systems, with
      placebo or an alternative delivery system in people with confirmed cystic
      fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently extracted data
      and assessed study quality. Authors of included studies were contacted and asked
      for any available additional data. Meta-analysis was limited due to differing
      study designs. MAIN RESULTS: Three randomised controlled trials met the inclusion
      criteria for this review, involving a total of 155 participants. Fourteen studies
      were excluded. The included studies differed in terms of CFTR gene replacement
      agent and study design, which limited the meta-analysis.Although the first Moss
      study reported a significant improvement in respiratory function (forced
      expiratory volume at one second) 30 days after participants had received their
      first dose of gene therapy agent, this finding was not confirmed in their larger
      second study or in our meta-analysis.In participants who received the CFTR gene
      transfer agents in the Alton study, "influenza-like" symptoms were found (risk
      ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other
      significant increases in adverse events in any of the studies.Alton measured ion
      transport in the lower airways and demonstrated significant changes toward normal
      values in the participants who received gene transfer agents (P < 0.0001), mean
      difference 6.86 (95% confidence interval 3.77 to 9.95). In these participants
      there was also evidence of increased salt transport in cells obtained by brushing
      the lower airway. These outcomes, whilst important, are not of direct clinical
      relevance. AUTHORS' CONCLUSIONS: There is currently no evidence to support the
      use of CFTR gene transfer agents as a treatment for lung disease in people with
      cystic fibrosis. Future studies need to investigate clinically important outcome
      measures.

PMID- 24282074
TI  - Variations of coronary hemodynamic responses to intravenous adenosine infusion:
      implications for fractional flow reserve measurements.
AB  - BACKGROUND: Continuous intravenous adenosine infusion reportedly produces stable
      and maximal hyperemia to allow for fractional flow reserve (FFR) measurement;
      however, several observers have noted variation of the coronary/aortic (Pd/Pa)
      pressure ratio during the course of an adenosine infusion. METHODS: Pd/Pa
      pressure recordings during continuous peripheral intravenous adenosine infusion
      were examined in 51 patients (68 measurements) with data collected for at least
      150 sec and for at least 30 sec after the lowest Pd/Pa reading. The lowest
      recorded Pd/Pa ratio was used as the true FFR value at maximal hyperemia. The
      highest subsequent Pd/Pa during the remaining period of adenosine infusion was
      recorded. A separate cohort of 12 patients had Pd/Pa values measured with both
      peripheral and central infusion. RESULTS: The average FFR value was 0.82 +/- 0.10
      and was recorded 99 +/- 33 sec into the infusion. The Pd/Pa value showed a
      subsequent average increase of 0.08 +/- 0.07 at 135 +/- 32 sec. From the lowest
      measurement, Pd/Pa changed from a ratio <=0.80 to >0.80 in 28% of recordings. In
      the cohort with matched recordings, central infusion reduced the severity (mean
      change of 0.08 vs. 0.11, P = 0.09) but not the incidence of Pd/Pa variability
      compared with peripheral infusion. CONCLUSION: Instability of Pd/Pa measurements
      is common over the course of a continuous intravenous adenosine infusion. FFR
      remains valid as the lowest value of Pd/Pa observed, however, Pd/Pa variability
      may subsequently occur and complicate pullback measurements for serial or
      multiple lesions.

PMID- 24282075
TI  - Masked thiol sugars: chemical behavior and synthetic applications of S
      glycopyranosyl-N-monoalkyl dithiocarbamates.
AB  - The chemical behavior of S-glycopyranosyl-N-monoalkyl dithiocarbamates (DTCs) as
      masked 1-glycosyl thiols, easily prepared by the nucleophilic displacement of 1
      halo sugars with dithiocarbamate salts of primary amines, has been studied and
      synthetically exploited. This behavior relies on the abstraction of the proton of
      the carbamate functionality that allows controlled access to thiolate sugar
      intermediates. The basic character of the DTC salts used as reagents leads to
      thiolates that evolve in situ to symmetrical diglycosyldisulfides (DGDSs) when
      long reaction times are allowed. Alternatively, controlled unmasking of the
      thiolate function can be efficiently attained by treatment with an external base
      of isolated anomeric glycosyl DTCs, the formation of which is prevalent when
      using short reaction times. In this manner, a second methodology for the
      preparation of symmetrical DGDSs and a chemical protocol for the S-glycosylation
      of any electrophilic substrate are established. The applications of this last
      strategy for the preparation of thioglycosyl vinyl sulfones, thiodisaccharides,
      and S-linked homo- and heterodivalent neoglycoconjugates are described as a proof
      of-concept of the great potential of the sugar DTCs in any chemical scenario in
      which the covalent attachment of a thiol sugar is required. The evaluation of the
      biological functionality of some divalent sulfurated sugar systems is also
      described.

PMID- 24282077
TI  - An in situ grazing incidence X-ray scattering study of block copolymer thin films
      during solvent vapor annealing.
AB  - In situ grazing-incidence small-angle X-ray scattering experiments on thin films
      of block copolymers during annealing in neutral solvent vapors are reported. By
      removing the solvent in a controlled manner, the period of the microphase
      separated morphology is found to increase with increasing block copolymer
      concentration in a power law manner with an exponent ~ 2/3. By venting the
      systems at different rates during the solvent removal process, kinetically
      arresting the system, the period of the microphase separated morphology in the
      dried film can be varied. 

PMID- 24282076
TI  - The glycosphingolipid hydrolases in the central nervous system.
AB  - Glycosphingolipids are a large group of complex lipids particularly abundant in
      the outer layer of the neuronal plasma membranes. Qualitative and quantitative
      changes in glycosphingolipids have been reported along neuronal differentiation
      and aging. Their half-life is short in the nervous system and their membrane
      composition and content are the result of a complex network of metabolic pathways
      involving both the de novo synthesis in the Golgi apparatus and the lysosomal
      catabolism. In particular, most of the enzymes of glycosphingolipid biosynthesis
      and catabolism have been found also at the plasma membrane level. Their action
      could be responsible for the fine tuning of the plasma membrane glycosphingolipid
      composition allowing the formation of highly specialized membrane areas, such as
      the synapses and the axonal growth cones. While the correlation between the
      changes of GSL pattern and the modulation of the expression/activity of different
      glycosyltransferases during the neuronal differentiation has been widely
      discussed, the role of the glycohydrolytic enzymes in this process is still
      little explored. For this reason, in the present review, we focus on the main
      glycolipid catabolic enzymes beta-hexosaminidases, sialidases, beta
      galactosidases, and beta-glucocerebrosidases in the process of the neuronal
      differentiation. 

PMID- 24282078
TI  - Preformulation study of highly purified inactivated polio vaccine, serotype 3.
AB  - To improve the effectiveness of the polio vaccination campaign, improvements in
      the thermal stability of the vaccine are being investigated. Here, inactivated
      polio vaccine, serotype 3 (IPV3) was characterized via a number of biophysical
      techniques. The size was characterized by transmission electronic microscopy and
      light scattering. The capsid protein conformation was evaluated by intrinsic
      fluorescence and circular dichroism (CD), and the D-antigen content by enzyme
      linked immunosorbent assay (ELISA). The pH thermal stability of IPV3 (pH 3.0-8.0;
      10 degrees C-87.5 degrees C) was evaluated by fluorescence, CD, and static light
      scattering. The transition temperatures reflect the responses, respectively, of
      tertiary structure, secondary structure, and size to applied thermal stress. The
      data were summarized as empirical phase diagrams, and the most stable conditions
      were found to be pH 7.0 with temperature lower than 40 degrees C. CD detected a
      higher transition temperature for capsid protein than that for RNA. The effects
      of certain excipients on IPV3 thermal stability and antigen content were
      evaluated. The results of their effects, based on intrinsic fluorescence and
      ELISA, were in good agreement, suggesting the feasibility of applying intrinsic
      fluorescence as a high-throughput tool for formulation development. The study
      improves the understanding of IPV3 thermal stability, and provides a starting
      point for future formulation development of IPV3 and other serotypes.

PMID- 24282079
TI  - A membrane model from implicit elasticity theory: application to visceral pleura.
AB  - A Fungean solid is derived for membranous materials as a body defined by
      isotropic response functions whose mathematical structure is that of a Hookean
      solid where the elastic constants are replaced by functions of state derived from
      an implicit, thermodynamic, internal energy function. The theory utilizes Biot's
      (Lond Edinb Dublin Philos Mag J Sci 27:468-489, 1939) definitions for stress and
      strain that, in one-dimension, are the stress/strain measures adopted by Fung (Am
      J Physiol 28:1532-1544, 1967) when he postulated what is now known as Fung's law.
      Our Fungean membrane model is parameterized against a biaxial data set acquired
      from a porcine pleural membrane subjected to three, sequential, proportional,
      planar extensions. These data support an isotropic/deviatoric split in the stress
      and strain-rate hypothesized by our theory. These data also demonstrate that the
      material response is highly nonlinear but, otherwise, mechanically isotropic.
      These data are described reasonably well by our otherwise simple, four-parameter,
      material model. 

PMID- 24282080
TI  - Skin-derived precursor Schwann cell myelination capacity in focal tibial
      demyelination.
AB  - INTRODUCTION: Skin-derived precursor cells (SKPs) are neural crest progenitor
      cells that can attain a Schwann cell-like phenotype through in vitro techniques
      (SKP-SCs). We hypothesized that SKP-SCs could produce mature myelin and, in doing
      so, facilitate the recovery of a focal demyelination injury. METHODS: We
      unilaterally injected DiI-labeled, green fluorescent protein (GFP)-producing SKP
      SCs into the tibial nerves of 10 adult Lewis rats (with contralateral media
      control), 9 days after bilateral doxorubicin injury (0.38 MUg). Tibial compound
      motor action potentials (CMAPs) were followed for 57 days. A separate
      morphometric cohort also included a Schwann cell injection group. RESULTS: SKP
      injected nerves recovered fastest in terms of electrophysiology and morphometry.
      SKP-SCs formed morphologically mature myelin, accounting for 15.3 +/- 5.3% of the
      total myelin in SKP-SC-injected nerves. CONCLUSIONS: SKP-SCs are robustly capable
      of myelination. They improve the recovery of a focal tibial nerve demyelination
      model by myelinating a measured percentage of axons.

PMID- 24282081
TI  - Complete nucleotide sequence of a norovirus GII.4 genotype: evidence for the
      spread of the newly emerged pandemic Sydney 2012 strain to China.
AB  - A newly emerged pandemic Sydney GII.4-like norovirus (NoV) (Jingzhou GII.4) was
      isolated in Jingzhou, China in April, 2013, demonstrating the rapid spread of the
      variant to China. The complete nucleotide sequence was compared with the
      prototype Sydney 2012 variant and its VP1 gene with that of Huzhou strain
      (isolated in January 2013 in Huzhou, China). The result demonstrates that the new
      variant has evolved rapidly, including mutations in the hypervariable P2 domain
      of the major capsid protein VP1. Our study also shows that the new Jingzhou GII.4
      variant co-circulated with GII.3 and GI.2 at the same time, supporting further
      monitoring of the evolution of the new NoV variant in China.

PMID- 24282082
TI  - Efficient long-distance NMR-PRE and EPR-DEER restraints for two-domain protein
      structure determination.

PMID- 24282083
TI  - Early invasive versus selectively invasive strategy in patients with non-ST
      segment elevation acute coronary syndrome: impact of age.
AB  - BACKGROUND: It is unclear whether the benefits of an early invasive strategy
      (EIS) in patients with non-ST-segment elevation acute coronary syndromes
      (NSTEACS) equally apply to younger and older individuals. Elderly patients are
      generally less likely to undergo EIS when compared with younger patients.
      OBJECTIVES: We conducted a meta-analysis to compare the benefit of an EIS versus
      a selectively invasive strategy (SIS) in patients with NSTEACS. We tested the
      hypothesis that the magnitude of benefit of an EIS over a SIS mainly applies to
      older individuals. METHODS: We extracted data from randomized controlled trials
      (RCTs) identified through search methodology filters. The primary outcome of the
      analysis was the composite of all-cause death and myocardial infarction (MI).
      Secondary outcomes were death and MI taken alone and re-hospitalization. RESULTS:
      Nine trials (n = 9,400 patients) were eligible. The incidence of the composite
      end-point of MI and all-cause death was 16.0% with the EIS and 18.3% with the SIS
      (OR: 0.85, 95% CI: 0.76-0.95). The incidence of MI was 8.4% with the EIS and
      10.9% with the SIS (OR: 0.75, 95% CI: 0.66-0.87). Similar results were obtained
      for rehospitalization (OR: 0.71, 95% CI: 0.55-0.90). The incidence of all-cause
      death did not differ between the two groups. The EIS reduced the composite end
      point and re-hospitalization to a greater extent in elderly than in younger
      patients (P for interaction = 0.044 and <0.0001, respectively). These findings
      were confirmed in meta-regression analyses. CONCLUSIONS: In patients with
      NSTEACS, a routine EIS reduces the risk of rehospitalization and the composite
      end point of recurrent MI and death to a greater extent in elderly than in
      younger individuals.

PMID- 24282084
TI  - Development of digestive enzyme activity in spotted rose snapper, Lutjanus
      guttatus (Steindachner, 1869) larvae.
AB  - We describe digestive enzyme activity during the larval development of spotted
      rose snapper, Lutjanus guttatus. Trypsin, chymotrypsin, leucine aminopeptidase,
      pepsin, amylase, lipase, and acid and alkaline phosphatase activities were
      evaluated using spectrophotometric techniques from hatching through 30 days. The
      spotted rose snapper larvae present the same pattern of digestive enzyme activity
      previously reported for other species in which pancreatic (i.e., trypsin,
      chymotrypsin, amylase, and lipase) and intestinal (i.e., acid and alkaline
      phosphatases and leucine aminopeptidase) enzymatic activities are present from
      hatching allowing the larvae to digest and absorb nutrients in the yolk-sac and
      live prey by the time of first feeding. The digestive and absorption capacity of
      the spotted rose snapper increases during the larval development. A significant
      increase in individual activity of all enzymes occurs at 20 DAH, and around 25
      DAH, the juvenile-type of digestion is observed with the appearance of pepsin
      secreted by the stomach, suggesting that maturation of the digestive function
      occurs around 20-25 DAH. Our results are in agreement with a previous suggestion
      that early weaning may be possible from 20 DAH. However, the patterns of
      enzymatic activities reported in our study should be considered during the
      formulation of an artificial diet for early weaning of the spotted rose snapper. 

PMID- 24282085
TI  - Comparative proton nuclear magnetic resonance studies of amantadine complexes
      formed in aqueous solutions with three major cyclodextrins.
AB  - Host-guest complexes of alpha-, beta-, and gamma-cyclodextrins (alpha-CD, beta
      CD, and gamma-CD, respectively) with amantadine (1-aminoadamantane, AMA; an
      antiviral agent) were characterized in aqueous solutions using proton nuclear
      magnetic resonance (NMR) spectroscopy. Host-guest molecular interactions were
      manifested by changes in the chemical shifts of AMA protons. NMR Job's plots
      showed that the stoichiometry of all the studied complexes was 1:1. Two
      dimensional T-ROESY experiments demonstrated that the complexes were formed by
      different degrees of incorporation of the adamantyl group of AMA into the CD
      cavity. The mode of AMA binding was proposed. The AMA molecule came into the
      alpha-CD cavity (the smallest size) or beta-CD cavity (the intermediate size)
      through its wide entrance to become shallowly or deeply accommodated,
      respectively. In the complex of AMA with gamma-CD (the largest cavity size), the
      adamantyl group was also quite deeply inserted into the CD cavity, but it arrived
      there through the narrow cavity entrance. It was found that the adamantyl group
      of AMA was best accommodated by the beta-CD cavity. The binding constants Kaa of
      the studied complexes (in M(-1) ), determined from DOSY NMR, were fairly high;
      their values in an ascending order were: alpha-CD (183) < gamma-CD (306) ? beta
      CD (5150).

PMID- 24282086
TI  - GSTT1 genetic polymorphism and susceptibility to childhood acute lymphoblastic
      leukemia: a meta-analysis.
AB  - Glutathione S-transferase T1 (GSTT1) genetic polymorphism has been considered as
      a risk factor for developing malignant diseases including acute lymphoblastic
      leukemia; however, the results from previous studies are inconsistent. We
      performed a meta-analysis of 16 published studies to investigate the association
      between GSTT1 null variant and risk of acute lymphoblastic leukemia in childhood.
      Between-study heterogeneity was assessed using the I (2) statistic method. Odds
      ratios (ORs) with corresponding 95 % confidence intervals (95 %CI) were pooled to
      assess the association. Those 16 studies were from 14 publications and included a
      total of 2,424 cases and 3,447 controls. Meta-analysis of a total of 16 studies
      showed that GSTT1 null variant was significantly associated with risk of
      childhood acute lymphoblastic leukemia (fixed-effect OR = 1.22, 95 %CI 1.07-1.39,
      P = 0.003, I (2) = 35 %). Subgroup analysis showed that GSTT1 null variant was
      significantly associated with risk of childhood acute lymphoblastic leukemia in
      Asians (fixed-effect OR = 1.47, 95 %CI 1.16-1.85, P = 0.001, I (2) = 0 %).
      However, there was no obvious association in both Caucasians (random-effect OR =
      1.07, 95 %CI 0.83-1.38, P = 0.59, I (2) = 53 %) and Africans (random-effect OR =
      0.99, 95 %CI 0.31-3.10, P = 0.98, I (2) = 72 %). Therefore, the GSTT1 null
      variant is significantly associated with susceptibility to childhood acute
      lymphoblastic leukemia in Asians.

PMID- 24282087
TI  - Steroid receptor co-activator-3 promotes osteosarcoma progression through up
      regulation of FoxM1.
AB  - Increasing evidence suggests that the three homologous members of steroid
      receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in
      enhancing cell proliferation in various human cancers, such as breast, prostate,
      and hepatocellular carcinoma. However, the function of SRC-3 in osteosarcoma
      remains largely unexplored. In the current study, we found that SRC-3, but not
      SRC-1 and SRC-2, was dramatically up-regulated in human osteosarcoma tissues,
      compared with adjacent normal tissues. To explore the functions of SRC-3 in
      osteosarcoma, in vitro studies were performed in MG63 and U2OS cells. SRC-3
      overexpression promoted osteosarcoma cell proliferation, whereas knockdown of SRC
      3 inhibits its proliferation. In support of these findings, we further
      demonstrated that SRC-3 up-regulated FoxM1 expression through co-activation of
      C/EBPgamma. Together our results show that SRC-3 drives osteosarcoma progression
      and imply it as a therapeutic target to abrogate osteosarcoma. 

PMID- 24282088
TI  - Clinicopathological characteristics and prognosis of gastric cancer with
      malignant ascites.
AB  - Management of gastric cancer with malignant ascites is a challenge, and limited
      data are available. We evaluated factors affecting survival for this condition to
      determine factors that predict survival outcome and to develop a rational
      treatment plan. We retrospectively studied 5,542 patients with gastric
      adenocarcinoma from January 2007 to December 2012. Among them, 347 patients
      (6.26%) were associated with malignant ascites. The patients' overall survival
      was compared among the different features. Three hundred forty-seven patients
      (153 females and 194 males; median age, 53 years) were enrolled, including 78
      (22.5%) young patients and 63 (18.1%) elderly patients. One hundred forty-three
      (41.2%) patients presented with malignant ascites at the initial diagnosis of
      gastric cancer, and 211 (60.8%) received chemotherapy. After a median follow-up
      duration of 10.4 months, the median survival after the diagnosis of malignant
      ascites was 5.2 months (95% CI, 4.8-5.6 months), and the 1-year survival rate was
      16.1 %. An ECOG score greater than 2 (P < 0.001), the presence of ascites with
      the diagnosis of gastric cancer (P < 0.001), no chemotherapy (P < 0.001), an
      albumin level less than 30 g/L (P = 0.013), an ascites volume greater than 2,000
      mL (P = 0.019), Helicobacter pylori infection (P = 0.010), and metastases to
      other organs (P = 0.037) were associated with poor prognosis, and they were all
      independent prognostic factors. The survival of gastric cancer patients with
      malignant ascites is relatively short, and ECOG score and the presence of ascites
      with the diagnosis of gastric cancer are the most important prognostic factors.
      Additionally, chemotherapy could improve the overall survival.

PMID- 24282089
TI  - Prediction of peritoneal recurrence by the mRNA level of CEA and MMP-7 in
      peritoneal lavage of gastric cancer patients.
AB  - A number of tumor markers had been reported to be useful in detecting free cancer
      cells in the peritoneal cavity and predict peritoneal recurrence in gastric
      cancer patients. The objective of this study was to compare the clinical impact
      of different tumor markers in peritoneal lavage fluid using the real-time
      quantitative reverse transcription polymerase chain reaction (RT-PCR) technique
      and to screen the most effective ones from them. The peritoneal lavage fluid of
      116 patients with gastric cancer was sampled at laparotomy. After RNA extraction
      and reverse transcription, real-time quantitative polymerase chain reaction (PCR)
      was performed using the primers and probes for carcinoembryonic antigen (CEA),
      cytokeratin-20, matrix metalloproteinase-7 (MMP-7), carbohydrate antigen 125, and
      transforming growth factor-beta-1. Among the 116 patients, 45 (38.8%) were
      confirmed to have peritoneal recurrence. Any of the PCR-positive results of the
      five tumor markers could predict peritoneal recurrence in the univariate analysis
      (P < 0.001). In the multivariate analysis, the PCR results of CEA (P = 0.003) and
      MMP-7 (P = 0.028) were found to be independent prognostic factors. A real-time
      quantitative RT-PCR analysis of the CEA and MMP-7 transcripts in peritoneal
      lavage fluid could effectively predict peritoneal recurrence in advanced gastric
      cancer patients who underwent a potentially curative resection.

PMID- 24282090
TI  - Ionic-liquid-nanoparticle hybrid electrolytes: applications in lithium metal
      batteries.
AB  - Development of rechargeable lithium metal battery (LMB) remains a challenge
      because of uneven lithium deposition during repeated cycles of charge and
      discharge. Ionic liquids have received intensive scientific interest as
      electrolytes because of their exceptional thermal and electrochemical
      stabilities. Ionic liquid and ionic-liquid-nanoparticle hybrid electrolytes based
      on 1-methy-3-propylimidazolium (IM) and 1-methy-3-propylpiperidinium (PP) have
      been synthesized and their ionic conductivity, electrochemical stability,
      mechanical properties, and ability to promote stable Li electrodeposition
      investigated. PP-based electrolytes were found to be more conductive and
      substantially more efficient in suppressing dendrite formation on cycled lithium
      anodes; as little as 11 wt % PP-IL in a PC-LiTFSI host produces more than a ten
      fold increase in cell lifetime. Both PP- and IM-based nanoparticle hybrid
      electrolytes provide up to 10 000-fold improvements in cell lifetime than
      anticipated based on their mechanical modulus alone. Galvanostatic cycling
      measurements in Li/Li4 Ti5 O12 half cells using IL-nanoparticle hybrid
      electrolytes reveal more than 500 cycles of trouble-free operation and enhanced
      rate capability. 

PMID- 24282091
TI  - Omega-3 fatty acids for cystic fibrosis.
AB  - BACKGROUND: Studies suggest that a diet rich in omega-3 essential fatty acids may
      have beneficial anti-inflammatory effects for chronic conditions such as cystic
      fibrosis. OBJECTIVES: To determine whether there is evidence that omega-3
      polyunsaturated fatty acid supplementation reduces morbidity and mortality and to
      identify any adverse events associated with supplementation. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials
      Register comprising references identified from comprehensive electronic database
      searches and handsearches of relevant journals and abstract books of conference
      proceedings. Authors and persons interested in the subject of the review were
      contacted.Date of last search: 08 July 2013. SELECTION CRITERIA: Randomised
      controlled trials in people with cystic fibrosis comparing omega-3 fatty acid
      supplements with placebo. DATA COLLECTION AND ANALYSIS: Two authors independently
      selected studies for inclusion, extracted data and assessed the risk of bias of
      the studies. MAIN RESULTS: The searches identified 14 studies; four studies with
      91 participants were included. Two studies were judged to be at low risk of bias
      based on adequate randomisation but this was unclear in the other two studies.
      Three of the studies adequately blinded patients, however, the risk of bias was
      unclear in all studies with regards to allocation concealment and selective
      reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks.
      One study compared a liquid dietary supplement containing omega-3 fatty acids to
      one without for six months. One study compared omega-3 fatty acids and omega-6
      fatty acids to a control (capsules with customised fatty acid blends) for three
      months. Only one short-term study (19 participants) comparing omega-3 to placebo
      reported a significant improvement in lung function and Shwachman score and a
      reduction in sputum volume in the omega-3 group. Another study (43 participants)
      demonstrated a significant increase in serum phospholipid essential fatty acid
      content and a significant drop in the n-6/n-3 fatty acid ratio following omega-3
      fatty acid supplementation compared to control. The longer-term study (17
      participants) demonstrated a significant increase in essential fatty acid content
      in neutrophil membranes and a significant decrease in the leukotriene B4 to
      leukotriene B5 ratio in participants taking omega-3 supplements compared to
      placebo. AUTHORS' CONCLUSIONS: This review found that regular omega-3 supplements
      may provide some benefits for people with cystic fibrosis with relatively few
      adverse effects, although evidence is insufficient to draw firm conclusions or
      recommend routine use of these supplements in people with cystic fibrosis. This
      review has highlighted the lack of data for many outcomes meaningful to people
      with or making treatment decisions about cystic fibrosis. A large, long-term,
      multicentre, randomised controlled study is needed to determine any significant
      therapeutic effect and to assess the influence of disease severity, dosage and
      duration of treatment. Future researchers should note the need for additional
      pancreatic enzymes.

PMID- 24282095
TI  - Crystalline polyethylene nanofibers with the theoretical limit of Young's
      modulus.
AB  - A highly crystalline polyethylene nanofiber is deflected by a cantilever under an
      atomic force microscope. The resulting approach and retract curves on both
      nanofiber and silicon substrate yield the Young's modulus of the nanofiber. The
      experiments show that the average Young's modulus of polyethylene nanofibers with
      diameters from 70 nm to 260 nm can be as high as 312 GPa. 

PMID- 24282096
TI  - Insights into the epithelial mesenchymal transition phenotype in cancer of
      unknown primary from a global microRNA profiling study.
AB  - PURPOSE: We sought to study the microRNA regulation of epithelial mesenchymal
      transition (EMT), the acquisition of migratory, mesenchymal-like properties of
      epithelial cells, in cancer of unknown primary (CUP). PATIENTS AND METHODS: We
      studied the global expression profile of 982 microRNAs by means of microarray
      technology in 68 CUP cases immunohistochemically characterised as EMT-positive (n
      = 5 by % of cells or n = 10 by a semiquantitative H-score) or EMT-negative.
      RESULTS: EMT-suppressive miRNAs such as miR-203 and members of the miR-200 family
      (miR-200a,b,c and miR-141) presented a 2.45 to 3.64-fold lower expression level
      in the EMT-positive cases without, however, reaching statistical significance.
      MiR-205, a squamous tissue-specific marker, was very variable in the data set.
      Excluding CUP cases with squamous cell histology, miR-205, miR-203 and the miR
      200 family exhibited a trend of downregulation in EMT-positive cases. A similar
      pattern of miRNA expression was detected when the comparison took place between
      EMT-positive vs EMT-negative cases according to the H-score. Moreover, miR-203,
      miR-205 and miR-200c were numerically downregulated in those tumours with high
      expression of the EMT marker N-cadherin. CONCLUSIONS: The EMT-suppressive miR-203
      and miR-200 family were consistently but non-significantly downregulated in CUP
      with the EMT phenotype. A larger study is warranted to further explore the role
      of microRNAs in CUP.

PMID- 24282097
TI  - Fusaric acid accelerates the senescence of leaf in banana when infected by
      Fusarium.
AB  - Fusarium oxysporum f.sp. cubense (FOC) is a causal agent of vascular wilt and
      leaf chlorosis of banana plants. Chloroses resulting from FOC occur first in the
      lowest leaves of banana seedlings and gradually progress upward. To investigate
      the responses of different leaf positions to FOC infection, hydroponic
      experiments with FOC inoculation were conducted in a greenhouse. Fusarium
      infected seedlings exhibited a decrease in net photosynthesis rate, stomatal
      conductance, and transpiration rate of all leaves. The wilting process in
      Fusarium-infected seedlings varied with leaf position. Measurements of the
      maximum photochemical efficiency of photosystem II (F(V)/F(max) and visualization
      with transmission electron microscopy showed a positive correlation between
      chloroplast impairment and severity of disease symptoms. Furthermore, results of
      malondialdehyde content and relative membrane conductivity measurements
      demonstrated that the membrane system was damaged in infected leaves.
      Additionally, the activities of phenylalanine ammonia-lyase, peroxidase and
      polyphenol oxidase were increased and total soluble phenolic compounds were
      significantly accumulated in the leaves of infected plants. The structural and
      biochemical changes of infected plants was consistent with plant senescence. As
      the FOC was not detected in infected leaves, we proposed that the chloroplast and
      membrane could be damaged by fusaric acid produced by Fusarium. During the
      infection, fusaric acid was first accumulated in the lower leaves and water
      soluble substances in the lower leaves could dramatically enhance fusaric acid
      production. Taken together, the senescence of infected banana plants was induced
      by Fusarium infection with fusaric acid production and the composition of
      different leaf positions largely contribute to the particular senescence process.

PMID- 24282098
TI  - Preparation of Li4Ti5O12 yolk-shell powders by spray pyrolysis and their
      electrochemical properties.
AB  - We have reported for the first time the preparation of yolk-shell-structured
      Li4Ti5O12 powders for use as anode materials in lithium-ion batteries. One
      Li4Ti5O12 yolk-shell-particle powder is directly formed from each droplet
      containing lithium, titanium, and carbon components inside the hot wall reactor
      maintained at 900  degrees C. The precursor Li4Ti5O12 yolk-shell-particle
      powders, which are directly prepared by spray pyrolysis, have initial discharge
      and charge capacities of 155 and 122 mA h g(-1) , respectively, at a current
      density of 175 mA g(-1) . Post-treatment of the yolk-shell-particle powders at
      temperatures of 700 and 800  degrees C improves the initial discharge and charge
      capacities. The initial discharge capacities of the Li4Ti5O12 powders with a yolk
      shell structure and a dense structure post-treated at 800  degrees C are 189 and
      168 mA h g(-1) , respectively. After 100 cycles, the corresponding capacities are
      172 and 152 mA h g(-1) , respectively (retentions of 91 and 90%).

PMID- 24282099
TI  - Cancer Prevention and Therapy: Integrating Traditional Korean Medicine Into
      Modern Cancer Care.
AB  - In spite of billions of dollars spent on cancer research each year, overall
      cancer incidence and cancer survival has not changed significantly in the last
      half century. Instead, the recent projection from the World Health Organization
      suggests that global cancer incidence and death is expected to double within the
      next decade. This requires an "out of the box" thinking approach. While
      traditional medicine used for thousands of years is safe and affordable, its
      efficacy and mechanism of action are not fully reported. Demonstrating that
      traditional medicine is efficacious and how it works can provide a "bed to bench"
      and "bench to bed" back approach toward prevention and treatment of cancer. This
      current review is an attempt to describe the contributions of traditional Korean
      medicine (TKM) to modern medicine and, in particular, cancer treatment. TKM
      suggests that cancer is an outcome of an imbalance of body, mind, and spirit;
      thus, it requires a multimodal treatment approach that involves lifestyle
      modification, herbal prescription, acupuncture, moxibustion, traditional
      exercise, and meditation to restore the balance. Old wisdoms in combination with
      modern science can find a new way to deal with the "emperor of all maladies." 

PMID- 24282100
TI  - Ganoderma lucidum spore induced CA72-4 elevation in gastrointestinal cancer: a
      five-case report.
AB  - GANODERMA LUCIDU: spore (GLS), an over-the-counter herbal supplement, is widely
      used by cancer patients in China. Although preclinical studies have shown it to
      be safe, complete safety data on GLS is still lacking. In this article, we report
      5 cases of gastrointestinal cancer that were treated with GLS plus multiple
      strategies between 2010 and 2011. These patients presented with increased levels
      of the serum tumor marker CA72-4, one of the most valuable markers for monitoring
      therapeutic response in patients receiving gastrointestinal cancer treatment,
      after oral ingestion of GLS twice a day for 1 or 2 months. Interestingly, CA72-4
      rapidly returned to normal levels when the patients discontinued the supplement
      and no change in clinical symptoms accompanied the CA72-4 surge. Taking into
      consideration that the underlying mechanism of this reaction is obscure, we
      suggest that additional studies are urgently needed and GLS be used with caution
      in cancer patients.

PMID- 24282101
TI  - Efficacy and Safety of Moxibustion for Relieving Pain in Patients With Metastatic
      Cancer: A Pilot, Randomized, Single-Blind, Sham-Controlled Trial.
AB  - BACKGROUND: Moxibustion has been traditionally used to manage pain related to
      chronic diseases, including cancer. This study aims to investigate the efficacy
      and safety of moxibustion for relieving cancer pain in patients with metastatic
      cancer. METHODS: A total of 16 patients were randomly divided into a true
      moxibustion (TM) group or a sham moxibustion (SM) group. In both groups,
      moxibustion was applied for 10 minutes, once daily for 7 consecutive days. In the
      SM group, the moxa cone was removed earlier than in the TM group, so as not to
      deliver heat stimulation completely into the skin. The changes of pain severity
      using the Brief Pain Inventory (BPI) and quality of life measured by the
      Functional Assessment of Cancer Therapy-General (FACT-G) were observed. A
      blinding credibility test was done to validate the sham moxibustion procedure.
      RESULTS: The total BPI score significantly decreased in the TM group compared
      with the SM group (TM vs SM: -0.97 +/- 1.05 vs 0.35 +/- 0.60,P= .025). The 2
      subsets of BPI, pain intensity score and pain interference score, also
      significantly decreased in the TM group (TM vs SM: intensity, -0.82 +/- 0.93 vs
      0.46 +/- 0.87,P= .020; interference, -1.12 +/- 1.31 vs 0.24 +/- 0.61,P= .047).
      Even after adjusting for the values of opioid consumption, these results remained
      significant. FACT-G did not significantly improve in the TM group. The blinding
      to sham moxibustion was credible and no serious adverse events occurred.
      CONCLUSION: We suggest that moxibustion could be a safe and potential modality
      for cancer-related pain in patients with metastatic cancer. With the limitation
      of small sample size, a larger and long-term follow-up study is necessary to
      determine more definitely the efficacy of moxibustion.

PMID- 24282102
TI  - Meta-Analysis of Randomized Controlled Trials of Acupuncture for Cancer-Related
      Fatigue.
AB  - BACKGROUND: Fatigue is a distressing and pervasive problem for people with
      cancer. In recent years, acupuncture has gained increasing attention among
      researchers as an alternative management strategy for cancer-related fatigue
      (CRF). This review aimed to evaluate the effectiveness of acupuncture for CRF.
      METHODS: Five databases (Medline, CINAHL, Scopus, the Cochrane Library, and CAJ
      Full-text Database) were searched up to May 2013. Randomized controlled trials
      (RCTs) of acupuncture for the treatment of CRF were considered for inclusion.
      RESULTS: Seven RCTs were included for meta-analysis, involving a total of 689
      subjects. Three studies compared acupuncture with sham acupuncture for CRF with
      follow-up at 10 weeks; the standardized mean difference (SMD) for general CRF
      change values was -0.82 (95% confidence interval [CI] = -1.90 to 0.26). When
      acupuncture plus education intervention was compared with usual care, there was a
      statistically significant difference for the change score of general CRF (SMD = 
      2.12; 95% CI = -3.21 to -1.03). The SMD for general CRF change scores between
      acupuncture with no treatment or wait-list control was -1.46 (95% CI = -3.56 to
      0.63). Finally, the SMD for general CRF change scores between acupuncture with
      acupressure or self-acupuncture was -1.12 (95% CI = -3.03 to 0.78). Three trials
      reported data for general quality of life and functioning status, reporting
      enough data for statistical pooling but showing no statistically significant
      difference (Zscore = 1.15,P= .25, SMD = 0.99, 95% CI = -0.70 to 2.68 andZscore =
      1.13,P= .26, SMD = 1.38, 95% CI = -1.02 to 3.79, respectively). TheI(2)statistics
      of all statistically pooled data were higher than 50%, indicating heterogeneity
      between the trials. CONCLUSIONS: There were 4 sets of comparison for the
      effectiveness of acupuncture for CRF; statistical pooling of the reduction in CRF
      from baseline to follow-up showed in favor of acupuncture. However, 3 sets of
      comparison for the pooled estimates of effect sizes had no statistical
      significance. Although one set of comparison (acupuncture plus education
      interventions vs usual care) had statistically significant differences, it is
      unclear whether this pooled positive outcome is attributable to the effects of
      acupuncture or to the education intervention. In addition, the duration of follow
      up in these included trials was up to 10 weeks, and some RCTs had methodological
      flaws. Further rigorously designed RCTs adhering to acceptable standards of trial
      methodology are required to determine the effectiveness of acupuncture and its
      long-term effects on CRF.

PMID- 24282103
TI  - Acupuncture for treatment of uncontrolled pain in cancer patients: a pragmatic
      pilot study.
AB  - PURPOSE: Pain control is an ongoing challenge in the oncology setting. Prior to
      implementing a large randomized trial at our institution, we investigated the
      feasibility, safety, and initial efficacy of acupuncture for uncontrolled pain
      among cancer patients. HYPOTHESES: Our hypotheses were that the acupuncture
      treatments provided would be ( : ) feasible, ( : ) safe, and ( : ) a beneficial
      adjunct to pain management. STUDY DESIGN: This was a single arm, nonrandomized
      pragmatic pilot study. METHODS: Participants experiencing pain >=4 on a 0 to 10
      numeric rating scale received a maximum of 10 treatments on an individualized
      basis. Recruitment, attrition, compliance, and adverse events (AEs) were
      assessed. Pain (Brief Pain Inventory-Short Form), quality of life (MD Anderson
      Symptom Inventory [MDASI]), and patient satisfaction were assessed at baseline
      and at the end of treatment. RESULTS: Of 115 patients screened, 52 (45%) were
      eligible and agreed to participate. Eleven (21%) were lost to follow-up, leaving
      41 who completed all study procedures. No AEs were reported. Mean pain SEVERIT:
      was 6.0 +/- 1.3 at baseline and 3.8 +/- 2.0 at follow-up ( : < .0001). Pain
      INTERFERENC: was 6.2 +/- 2.3 at baseline and 4.3 +/- 2.8 at follow-up ( : <
      .0011). On the MDASI, the mean symptom SEVERIT: was 4.6 +/- 1.8 at baseline and
      3.2 +/- 1.9 at follow-up ( : < .0001), and mean symptom INTERFERENC: was 5.8 +/-
      2.4 at baseline and 4.1 +/- 2.9 at follow-up ( : < .002). Prescribed pain
      medications decreased across the course of the study. Patient satisfaction was
      high: 87% reported that their expectations were met "very well" or "extremely
      well"; 90% said they were likely to participate again; 95% said they were likely
      to recommend acupuncture to others; and 90% reported they found the service to be
      "useful" or "very useful." CONCLUSIONS: Acupuncture was feasible, safe, and a
      helpful treatment adjunct for cancer patients experiencing uncontrolled pain in
      this study. Randomized placebo-controlled trials are needed to confirm these
      results.

PMID- 24282104
TI  - Effects of switching from insulin glargine or detemir to insulin degludec in
      patients with type 1 diabetes mellitus.
AB  - INTRODUCTION: Insulin degludec is a new, ultra-long-acting basal insulin. The aim
      of this study was to analyze the changes of basal insulin dose and blood glucose
      profile in basal-bolus therapy of type 1 diabetes mellitus (T1DM) at the
      switching of basal insulin from insulin glargine or detemir to insulin degludec.
      METHODS: Sixteen patients with T1DM were enrolled. The patients underwent
      continuous glucose monitoring before and after the switching of insulin glargine
      or detemir to degludec. Ten patients treated with insulin glargine or detemir
      twice daily, were switched to insulin degludec with 80-90% of the prior insulin
      dose. The remaining six patients treated with insulin glargine once daily, were
      switched to insulin degludec without down titration. The changes of daily insulin
      dose and glycated hemoglobin (HbA1c) were also examined for 12 weeks after
      switching to insulin degludec. RESULTS: In the patients switched from twice-daily
      basal insulin, no significant difference was found between before and after
      switching in the blood glucose profile. In the once-daily group, blood glucose
      levels showed a tendency to decrease after switching to the degludec treatment.
      During the study period, total daily insulin dose (TDD) and total daily basal
      insulin dose (TBD) decreased significantly in the twice-daily group, and TDD and
      TBD showed a tendency to decrease after switching to degludec in the once-daily
      group. In both groups, the changes of HbA1c were not significantly different.
      CONCLUSION: It is possible to achieve similar glycemic control with once-daily
      injection and lower doses of insulin degludec in patients with T1DM who have been
      treated with insulin glargine or detemir.

PMID- 24282106
TI  - Steric-repulsion-based magnetically responsive photonic crystals.
AB  - The first steric-repulsion-based magnetically responsive photonic crystals
      (MRPCs) is constructed by synthesizing uniform superparamagnetic
      polyvinylpyrrolidone-coated Fe3 O4 colloidal nanocrystal clusters. The color
      tunable range of the MRPCs can not only cover almost the entire visible specztrum
      in solvents of diverse polarities, but also is insusceptible to ionic strength or
      pH values, facilitating the practical applications of MRPCs. 

PMID- 24282105
TI  - Impact of in-hospital bleeding according to the Bleeding Academic Research
      Consortium classification on the long-term adverse outcomes in patients
      undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: The aim of this study was to assess the impact of bleeding after
      percutaneous coronary intervention (PCI) with drug-eluting stents on long-term
      clinical events according to the newly proposed Bleeding Academic Research
      Consortium (BARC) classification. BACKGROUND: Current evidence about the impact
      of the BARC classification is limited. METHODS: Out of a total of 6,166 patients
      who underwent PCI in a prospective IRIS-DES registry, the impact of in-hospital
      bleeding defined as the BARC classification on major adverse cardiovascular
      events (MACE) comprising death, myocardial infarction (MI), or stroke was
      analyzed. RESULTS: In-hospital bleeding occurred in 235 patients (3.8%) according
      to BARC classification. During the 2-year follow-up, MACE occurred in 599
      patients (9.7%). The 2-year incidence of MACE was significantly higher in
      patients with bleeding (16.7% vs. 8.3%; adjusted hazard ratio [HR], 1.6; 95%
      confidence interval [CI], 1.2-2.3; P = 0.002) than in those without bleeding. We
      observed a higher risk of MI (12.4% vs. 6.4%; adjusted HR, 1.7; 95% CI, 1.2-2.6,
      P = 0.005), stroke (3.0% vs. 0.6%; adjusted HR, 2.9; 95% CI, 1.4-6.2, P = 0.005)
      in patients with bleeding. Death (3.8% vs. 1.6%; adjusted HR, 1.6; 95% CI, 0.9
      3.0, P = 0.120) and target vessel revascularization (4.3% vs. 1.9%; adjusted HR,
      1.6; 95% CI, 0.9-2.9, P = 0.108) were statistically insignificant. Incidence,
      adjusted HR and P-value were similar between BARC and TIMI classification.
      CONCLUSIONS: In-hospital bleeding events according to the newly proposed BARC
      definition were significantly associated with an increased risk of adverse long
      term events in patients undergoing PCI with drug-eluting stents. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 24282107
TI  - A reusable unsupported rhenium nanocrystalline catalyst for acceptorless
      dehydrogenation of alcohols through gamma-C-H activation.
AB  - Rhenium nanocrystalline particles (Re NPs), of 2 nm size, were prepared from
      NH4ReO4 under mild conditions in neat alcohol. The unsupported Re NPs convert
      secondary and benzylic alcohols to ketones and aldehydes, respectively, through
      catalytic acceptorless dehydrogenation (AD). The oxidant- and acceptor-free neat
      dehydrogenation of alcohols to obtain dihydrogen gas is a green and atom
      economical process for making carbonyl compounds. Secondary aliphatic alcohols
      give quantitative conversion and yield. Transmission electron microscopy (TEM), X
      ray photoelectron spectroscopy (XPS), Re K-edge X-ray absorption near-edge
      structure (XANES), and X-ray absorption fine structure (EXAFS) data confirmed the
      characterization of the Re NPs as metallic rhenium with surface oxidation to
      rhenium(IV) oxide (ReO2). Isotope labeling experiments revealed a novel gamma-CH
      activation mechanism for AD of alcohols.

PMID- 24282108
TI  - Identification of inflamed atherosclerotic lesions in vivo using PET-CT.
AB  - Inflammation plays a major pathogenetic role in the development of
      atherosclerotic plaques and related thromboembolic events. The identification of
      vulnerable plaques is of the utmost importance, as this may allow the
      implementation of more effective preventive and therapeutic interventions.
      Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be
      useful for tracing inflammation within plaques. However, its relationship to
      immunohistochemical findings in different territories of the peripheral
      circulation was not completely elucidated. We aimed to determine whether plaque
      inflammation could be measured by PET in combination with computer tomography
      (CT) using FDG and what is the relationship between FDG uptake and
      immunohistochemical findings in the removed atherosclerotic lesions of the
      femoral and carotid arteries. The study included 31 patients, 21 patients with
      high-grade stenosis of the internal carotid artery (ICA) and 10 patients with
      occlusion of the common femoral artery (CFA), all of whom underwent
      endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was
      performed. FDG uptake was measured as the maximum blood--normalized standardized
      uptake value, known as the target to background ratio (TBR max). TBR max amounted
      to 1.72 +/- 0.8, and in patients with ICA, stenosis was not significantly
      different from patients with CFA occlusion. Immunohistochemical and morphometric
      analyses of the plaques obtained at endarterectomy showed that the density of T
      lymphocytes and macrophages (number of cells per square millimeter) was
      significantly higher in subjects with stenosis of the ICA than in subjects with
      occlusion of the femoral arteries: lymphocytes, 1.26 +/- 0.21 vs. 0.77 +/- 0.29;
      p = 0.02 and macrophages, 1.01 +/- 0.18 vs. 0.69 +/- 0.23; p = 0.003. In the
      whole group of patients, the density of inflammatory cells significantly
      correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r = 0.60; p
      < 0.01 and macrophages, r = 0.65; p < 0.01. The results of our study show that
      FDG uptake is related to the accumulation of inflammatory cells in
      atherosclerotic lesions. This finding suggests that FDG uptake reflects the
      severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it
      could be an indicator of their vulnerability. However, data from large outcome
      studies is needed to estimate the usefulness of this technique in identifying the
      most dangerous atherosclerotic lesions and vulnerable patients.

PMID- 24282109
TI  - Peri-infarct zone characterized by cardiac magnetic resonance imaging is directly
      associated with the inflammatory activity during acute phase myocardial
      infarction.
AB  - Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI)
      and the extent of the peri-infarct zone characterized by cardiac magnetic
      resonance imaging (CMRi) are both associated with increased risk of life
      threatening arrhythmias and sudden cardiac death. The present study investigated
      the existence of association between these two phenomena in 98 patients (55 +/-
      10 years) with ST segment elevation MI. Plasma levels of C-reactive protein
      (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on
      admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks
      after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in
      CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor
      necrosis factor type alpha (TNF-alpha; 4.6 vs. 3.9 times; p = 0.001) were higher
      in patients with PIZ above the median than in the counterparts. PIZ was
      correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta
      IL-2 (r = 0.6), TNF-alpha (r = 0.5), delta-TNF-alpha (r = 0.4; p = 0.0001).
      Enhanced activation of SIA during the acute phase of MI is directly related with
      generation of PIZ. 

PMID- 24282110
TI  - In vivo pump-probe optical coherence tomography imaging in Xenopus laevis.
AB  - Currently, optical coherence tomography (OCT), is not capable of obtaining
      molecular information often crucial for identification of disease. To enable
      molecular imaging with OCT, we have further developed a technique that harnesses
      transient changes in light absorption in the sample to garner molecular
      information. A Fourier-domain Pump-Probe OCT (PPOCT) system utilizing a 532 nm
      pump and 830 nm probe has been developed for imaging hemoglobin. Methylene blue,
      a biological dye with well-know photophysics, was used to characterize the system
      before investigating the origin of the hemoglobin PPOCT signal. The first in vivo
      PPOCT images were recorded of the vasculature in Xenopus laevis. The technique
      was shown to work equally well in flowing and nonflowing vessels. Furthermore,
      PPOCT was compared with other OCT extensions which require flow, such as Doppler
      OCT and phase-variance OCT. PPOCT was shown to better delineate tortuous vessels,
      where nodes often restrict Doppler and phase-variance reconstruction.

PMID- 24282111
TI  - Kawasaki disease associated with neuroblastoma: evidence for a new paraneoplastic
      syndrome?

PMID- 24282112
TI  - Smartphone and tablet self management apps for asthma.
AB  - BACKGROUND: Asthma is one of the most common long-term conditions worldwide,
      which places considerable pressure on patients, communities and health systems.
      The major international clinical guidelines now recommend the inclusion of self
      management programmes in the routine management of patients with asthma. These
      programmes have been associated with improved outcomes in patients with asthma.
      However, the implementation of self management programmes in clinical practice,
      and their uptake by patients, is still poor. Recent developments in mobile
      technology, such as smartphone and tablet computer apps, could help develop a
      platform for the delivery of self management interventions that are highly
      customisable, low-cost and easily accessible. OBJECTIVES: To assess the
      effectiveness, cost-effectiveness and feasibility of using smartphone and tablet
      apps to facilitate the self management of individuals with asthma. SEARCH
      METHODS: We searched the Cochrane Airways Group Register (CAGR), the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO,
      CINAHL, Global Health Library, Compendex/Inspec/Referex, IEEEXplore, ACM Digital
      Library, CiteSeer(x) and CAB abstracts via Web of Knowledge. We also searched
      registers of current and ongoing trials and the grey literature. We checked the
      reference lists of all primary studies and review articles for additional
      references. We searched for studies published from 2000 onwards. The latest
      search was run in June 2013. SELECTION CRITERIA: We included parallel randomised
      controlled trials (RCTs) that compared self management interventions for patients
      with clinician-diagnosed asthma delivered via smartphone apps to self management
      interventions delivered via traditional methods (e.g. paper-based asthma
      diaries). DATA COLLECTION AND ANALYSIS: We used standard methods expected by the
      Cochrane Collaboration. Our primary outcomes were symptom scores; frequency of
      healthcare visits due to asthma exacerbations or complications and health-related
      quality of life. MAIN RESULTS: We included two RCTs with a total of 408
      participants. We found no cluster RCTs, controlled before and after studies or
      interrupted time series studies that met the inclusion criteria for this
      systematic review. Both RCTs evaluated the effect of a mobile phone-based asthma
      self management intervention on asthma control by comparing it to traditional,
      paper-based asthma self management. One study allowed participants to keep daily
      entries of their asthma symptoms, asthma medication usage, peak flow readings and
      peak flow variability on their mobile phone, from which their level of asthma
      control was calculated remotely and displayed together with the corresponding
      asthma self management recommendations. In the other study, participants recorded
      the same readings twice daily, and they received immediate self management
      feedback in the form of a three-colour traffic light display on their phones.
      Participants falling into the amber zone of their action plan twice, or into the
      red zone once, received a phone call from an asthma nurse who enquired about the
      reasons for their uncontrolled asthma.We did not conduct a meta-analysis of the
      data extracted due to the considerable degree of heterogeneity between these
      studies. Instead we adopted a narrative synthesis approach. Overall, the results
      were inconclusive and we judged the evidence to have a GRADE rating of low
      quality because further evidence is very likely to have an important impact on
      our confidence in the estimate of effect and is likely to change the estimate. In
      addition, there was not enough information in one of the included studies to
      assess the risk of bias for the majority of the domains. Although the other
      included study was methodologically rigorous, it was not possible to blind
      participants or personnel in the study. Moreover, there are concerns in both
      studies in relation to attrition bias and other sources of bias.One study showed
      that the use of a smartphone app for the delivery of an asthma self management
      programme had no statistically significant effect on asthma symptom scores (mean
      difference (MD) 0.01, 95% confidence interval (CI) -0.23 to 0.25), asthma-related
      quality of life (MD of mean scores 0.02, 95% CI -0.35 to 0.39), unscheduled
      visits to the emergency department (OR 7.20, 95% CI 0.37 to 140.76) or frequency
      of hospital admissions (odds ratio (OR) 3.07, 95% CI 0.32 to 29.83). The other
      included study found that the use of a smartphone app resulted in higher asthma
      related quality of life scores at six-month follow-up (MD 5.50, 95% CI 1.48 to
      9.52 for the physical component score of the SF-12 questionnaire; MD 6.00, 95% CI
      2.51 to 9.49 for the mental component score of the SF-12 questionnaire), improved
      lung function (PEFR) at four (MD 27.80, 95% CI 4.51 to 51.09), five (MD 31.40,
      95% CI 8.51 to 54.29) and six months (MD 39.20, 95% CI 16.58 to 61.82), and
      reduced visits to the emergency department due to asthma-related complications
      (OR 0.20, 95% CI 0.04 to 0.99). Both studies failed to find any statistical
      differences in terms of adherence to the intervention and occurrence of other
      asthma-related complications. AUTHORS' CONCLUSIONS: The current evidence base is
      not sufficient to advise clinical practitioners, policy-makers and the general
      public with regards to the use of smartphone and tablet computer apps for the
      delivery of asthma self management programmes. In order to understand the
      efficacy of apps as standalone interventions, future research should attempt to
      minimise the differential clinical management of patients between control and
      intervention groups. Those studies evaluating apps as part of complex,
      multicomponent interventions, should attempt to tease out the relative
      contribution of each intervention component. Consideration of the theoretical
      constructs used to inform the development of the intervention would help to
      achieve this goal. Finally, researchers should also take into account: the role
      of ancillary components in moderating the observed effects, the seasonal nature
      of asthma and long-term adherence to self management practices.

PMID- 24282113
TI  - Factors influencing the response of psychological symptoms to continuous positive
      airway pressure therapy.
AB  - PURPOSE: To examine whether in obstructive sleep apnea (OSA) patients the degree
      of sleepiness, slow-wave sleep (SWS) loss, and hypoxia influence the response of
      psychological symptoms to continuous positive airway pressure (CPAP) therapy.
      METHODS: A prospectively planned cohort was assessed. Participants underwent full
      overnight polysomnography. All answered the Symptom Checklist-90-Revised (SCL-90)
      and the Epworth sleepiness scale (ESS). Only cases with an apnea-hypopnea index
      <=60 events/h were 24 invited to participate. In an interview by telephone, after
      a follow-up period between 2 months and 1 year, patients informed whether they
      were in treatment with CPAP or remained voluntarily untreated. Subjects who
      accepted to participate answered for the second time the SCL-90 and the ESS. The
      baseline variables of interest were: (a) score of the ESS, (b) duration of SWS,
      and (c) time with arterial oxygen saturation below 90%. The outcomes were the
      change in SCL-90 scores in all dimensions and indices of the questionnaire.
      RESULTS: A number of 73 patients, mostly men, were included. In uncontrolled
      analyses, CPAP-treated patients showed significant improvement at follow-up in 10
      of the 13 SCL-90 scores. Comparing with the control group, only six scores were
      improved. Baseline sleepiness was the best predictor of SCL-90 improvement after
      CPAP treatment in the univariate analyses, and the only significant predictor of
      improvement in a multivariate regression model. CONCLUSIONS: Sleepiness may
      supersede other factors that influence psychological improvement in CPAP-treated
      patients with severe OSA.

PMID- 24282115
TI  - Super long-life supercapacitors based on the construction of nanohoneycomb-like
      strongly coupled CoMoO(4)-3D graphene hybrid electrodes.
AB  - Nanohoneycomb-like strongly coupled CoMoO4 -3D graphene hybird electrodes are
      synthesized for supercapacitors which exhibit excellent specific capacitance and
      superior long-term cycle stability. The supercapacitor device can power a 5 mm
      diameter LED efficiently for more than 3 min with a charging time of only 2 s,
      and shows high energy densities and good cycle stability. 

PMID- 24282114
TI  - Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory
      responses in acetaminophen-induced acute liver failure.
AB  - Acetaminophen-induced acute liver failure (AALF) is characterized both by
      activation of innate immune responses and susceptibility to sepsis. Circulating
      monocytes and hepatic macrophages are central mediators of inflammatory responses
      and tissue repair processes during human AALF. Secretory leukocyte protease
      inhibitor (SLPI) modulates monocyte/macrophage function through inhibition of
      nuclear factor kappa B (NF-kappaB) signaling. The aims of this study were to
      establish the role of SLPI in AALF. Circulating levels of SLPI, monocyte cluster
      of differentiation 163 (CD163), human leukocyte antigen-DR (HLA-DR), and
      lipopolysaccharide (LPS)-stimulated levels of NF-kappaBp65, tumor necrosis factor
      alpha (TNF-alpha) and interleukin (IL)-6 were determined in patients with AALF,
      chronic liver disease, and healthy controls. Immunohistochemistry and
      multispectral imaging of AALF explant tissue determined the cellular sources of
      SLPI and hepatic macrophage phenotype. The phenotype and function of monocytes
      and macrophages was determined following culture with recombinant human (rh)
      SLPI, liver homogenates, and plasma derived from AALF patients in the presence
      and absence of antihuman (alpha)SLPI. Hepatic and circulatory concentrations of
      SLPI were elevated in AALF and immunohistochemistry revealed SLPI expression in
      biliary epithelial cells and within hepatic macrophages (h-mpsi) in areas of
      necrosis. H-mpsi and circulating monocytes in AALF exhibited an anti-inflammatory
      phenotype and functional characteristics; typified by reductions in NF-kappaBp65,
      TNF-alpha, and IL-6 and preserved IL-10 secretion following LPS challenge.
      Culture of healthy monocytes with AALF liver homogenates, plasma, or rhSLPI
      induced monocytes with strikingly similar anti-inflammatory characteristics which
      were reversed by inhibiting the activity of SLPI. CONCLUSION: SLPI is a pivotal
      mediator of anti-inflammatory responses in AALF through modulation of
      monocyte/macrophage function, which may account for the susceptibility to sepsis
      in AALF.

PMID- 24282116
TI  - Influence of rare earth elements (Y, Gd and Lu) on the luminescent properties of
      green phosphor ZnMoO4:Tb3+.
AB  - (Zn,Lnx )MoO4 :Tb(3+) (Ln = Y(3+), Gd(3+) and Lu(3+) ) were prepared using the co
      precipitation method. Phase impurity, morphology and composition were
      investigated by power X-ray diffraction (XRD), scanning electron microscopy (SEM)
      and energy dispersive spectroscopy (EDS). The experimental results show that
      crystal structure is not destroyed after doping an appropriate amount of Y(3+),
      Gd(3+) and Lu(3+). EDS analysis reveals that Y, Gd and Lu have been successfully
      doped into ZnMoO4 . In addition, the morphology of the phosphors is notably
      improved, exhibiting homogeneous dispersion morphology and irregular shapes of
      particle size ~ 0.5-1 um. The luminescent intensity of (Zn,Lnx )MoO4:Tb(3+) (Ln =
      Y(3+), Gd(3+) and Lu(3+)) phosphor is obviously higher than that of ZnMoO4
      :Tb(3+) phosphor. The energy transfer process between trivalent rare earth ions
      indicates that the inert earth ions can act as an energy bridge from MoO4(2-) to
      Tb(3+).

PMID- 24282117
TI  - A mixed molecular building block strategy for the design of nested polyhedron
      metal-organic frameworks.
AB  - A mixed molecular building block (MBB) strategy for the synthesis of double
      walled cage-based porous metal-organic frameworks (MOFs) is presented. By means
      of this method, two isostructural porous MOFs built from unprecedented double
      walled metal-organic octahedron were obtained by introducing two size-matching C3
      -symmetric molecular building blocks with different rigidities. With their unique
      framework structures, these MOFs provide, to the best of our knowledge, the first
      examples of double-walled octahedron-based MOFs. 

PMID- 24282118
TI  - Reply: Legislation of embryo transfer affected the denominator, not the
      numerator!

PMID- 24282119
TI  - Legislation of embryo transfer affected the denominator, not the numerator!

PMID- 24282120
TI  - The impact of legally restricted embryo transfer and reimbursement policy on
      cumulative delivery rate after treatment with assisted reproduction technology.
AB  - STUDY QUESTION: What is the impact of the Belgian legislation (1 July 2003),
      coupling reimbursement of six assisted reproduction technology (ART) cycles per
      patient to restricted embryo transfer policy, on cumulative delivery rate (CDR)
      per patient? SUMMARY ANSWER: The introduction of Belgian legislation in ART had
      no negative impact on the CDR per patient based on realistic estimates within six
      cycles or 36 months. WHAT IS KNOWN ALREADY: The introduction of Belgian
      legislation limiting the number of embryos for transfer resulted in a reduction
      of the multiple pregnancy rate (MPR) per cycle by 50%. STUDY DESIGN, SIZE,
      DURATION: A retrospective cohort study with a study group after implementation of
      the new ART legislation (July 2003 to June 2006) and the control group, before
      legislation (July 1999 to June 2002). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      CDR was compared in an academic tertiary setting between a study group after
      legislation (n = 795 patients, 1927 fresh and 383 frozen-thawed embryo transfer
      (FET) cycles) and a control group before legislation (n = 463 patients, 876 fresh
      and 185 FET cycles) within six cycles or 36 months, delivery or discontinuation
      of treatment. The CDR was estimated using life table analysis considering
      pessimistic, optimistic and realistic scenarios and compared after adjustment for
      confounding variables. In the realistic scenario we included information on
      embryo quality to define the prognosis of each patient discontinuing treatment.
      MAIN RESULTS AND THE ROLE OF CHANCE: In the realistic scenario, CDR within 36
      months was comparable (all ages, P = 0.221) in study group (60.8%) and control
      group (65.6%), as well as in different age groups (<36 years, P = 0.242; 36-39
      years, P = 0.851; 40-42 years, P = 0.840). In the realistic scenario applied to
      six cycles, we found lower CDRs in the study group than in the control group
      within the two first cycles (all ages, P = 0.009; <36 years, P = 0.007) but no
      difference in CDRs between the two groups within the four subsequent cycles (all
      ages P = 0.232; <36 years, P = 0.198). The CDR within six cycles was 60 and 65.3%
      for study group and control group, respectively, for all ages, and 65.8 and
      70.4%, respectively, in the subgroup younger than 36 years. In women >=36 years,
      CDR within six cycles was comparable in both groups (36-39 years, 43% in study
      versus 44.4% in control group, P = 0.730; 40-42 years, 21% in study versus 23% in
      control group, P = 0.786). LIMITATIONS, REASONS FOR CAUTION: A retrospective
      cohort study design was the only way to study the impact of legislation on CDR.
      Owing to the retrospective nature of this analysis over a long period of time,
      our data are potentially influenced by improvements in techniques and therefore
      improved success rates in ART over time. WIDER IMPLICATIONS OF THE FINDINGS: This
      'Belgian model' can now be considered for application worldwide in countries with
      the aim to reduce the main ART side effect (high MPR) and its associated costs
      without a negative effect on the main intended effect (high CDR). STUDY
      FUNDING/COMPETING INTEREST(S): The authors have no conflict of interest to
      declare. No funding was obtained for this study.

PMID- 24282121
TI  - Designing clinical trials for dystonia.
AB  - With advances in the understanding of the pathophysiology of dystonia, novel
      therapeutics are being developed. Such therapies will require clinical
      investigation ranging from exploratory studies to examine safety, tolerability,
      dosage selection, and preliminary efficacy to confirmatory studies to evaluate
      efficacy definitively. As dystonia is a rare and complex disorder with clinical
      and etiological heterogeneity, clinical trials will require careful consideration
      of the trial design, including enrollment criteria, concomitant medication use,
      and outcome measures. Given the complexities of designing and implementing
      efficient clinical trials, it is important for clinicians and statisticians to
      collaborate closely throughout the clinical development process and that each has
      a basic understanding of both the clinical and statistical issues that must be
      addressed. To facilitate designing appropriate clinical trials in this field, we
      review important general clinical trial and regulatory principles, and discuss
      the critical components of trials with an emphasis on considerations specific to
      dystonia. Additionally, we discuss designs used in early exploratory, late
      exploratory, and confirmatory phases, including adaptive designs. 

PMID- 24282123
TI  - Structure and properties of chimeric small heat shock proteins containing yellow
      fluorescent protein attached to their C-terminal ends.
AB  - Recombinant chimeras of small heat shock proteins (sHsp) HspB1, HspB5, and HspB6
      containing enhanced yellow fluorescent protein (EYFP) attached to their C
      terminal ends were constructed and purified. Some properties of these chimeras
      were compared with the corresponding properties of the same chimeras containing
      EYFP attached to the N-terminal end of sHsp. The C-terminal fluorescent chimeras
      of HspB1 and HspB5 tend to aggregate and form a heterogeneous mixture of
      oligomers. The apparent molecular weight of the largest C-terminal chimeric
      oligomers was higher than that of the corresponding N-terminal chimeras or of the
      wild-type proteins; however, both homooligomers of N-terminal chimeras and
      homooligomers of C-terminal chimeras contained fewer subunits than the wild-type
      HspB1 or HspB5. Both N-terminal and C-terminal chimeras of HspB6 form small
      oligomers with an apparent molecular weight of 73-84 kDa. The C-terminal chimeras
      exchange their subunits with homologous wild-type proteins. Heterooligomers
      formed by the wild-type HspB1 (or HspB5) and the C-terminal chimeras of HspB6
      differ in size and composition from heterooligomers formed by the corresponding
      wild-type proteins. As a rule, the N-terminal chimeras possess similar or
      slightly higher chaperone-like activity than the corresponding wild-type
      proteins, whereas the C-terminal chimeras always have a lower chaperone-like
      activity than the wild-type proteins. It is concluded that attachment of EYFP to
      either N-terminal or C-terminal ends of sHsp affects their oligomeric structure,
      their ability to form heterooligomers, and their chaperone-like activity.
      Therefore, the data obtained with fluorescent chimeras of sHsp expressed in the
      cell should be interpreted with caution. 

PMID- 24282124
TI  - A review of the preparation and application of flavour and essential oils
      microcapsules based on complex coacervation technology.
AB  - This paper briefly introduces the preparation and application of flavour and
      essential oils microcapsules based on complex coacervation technology. The
      conventional encapsulating agents of oppositely charged proteins and
      polysaccharides that are used for microencapsulation of flavours and essential
      oils are reviewed along with the recent advances in complex coacervation methods.
      Proteins extracted from animal-derived products (gelatin, whey proteins, silk
      fibroin) and from vegetables (soy proteins, pea proteins), and polysaccharides
      such as gum Arabic, pectin, chitosan, agar, alginate, carrageenan and sodium
      carboxymethyl cellulose are described in depth. In recent decades, flavour and
      essential oils microcapsules have found numerous potential practical applications
      in food, textiles, agriculturals and pharmaceuticals. In this paper, the
      different coating materials and their application are discussed in detail.
      Consequently, the information obtained allows criteria to be established for
      selecting a method for the preparation of microcapsules according to their
      advantages, limitations and behaviours as carriers of flavours and essential
      oils.

PMID- 24282125
TI  - Editorial: molecular endocrinology articles in the spotlight for December 2013.

PMID- 24282122
TI  - The role of dendritic cells in driving genital tract inflammation and HIV
      transmission risk: are there opportunities to intervene?
AB  - Effective prevention of new HIV infections will require an understanding of the
      mechanisms involved in HIV acquisition. HIV transmission across the female
      genital tract is the major mode of new HIV infections in sub-Saharan Africa and
      involves complex processes, including cell activation, inflammation and
      recruitment of HIV target cells. Activated CD4(+) T-cells, dendritic cells (DC)
      and macrophages have been described as targets for HIV at the genital mucosa.
      Activation of these cells may occur in the presence of sexually-transmitted
      infections, disturbances of commensal flora and other inflammatory processes. In
      this review, we discuss causes and consequences of inflammation in the female
      genital tract, with a focus on DC. We describe the central role these cells may
      play in facilitating or preventing HIV transmission across the genital mucosa,
      and in the initial recognition of HIV and other pathogens, allowing activation of
      an adaptive immune response to infection. We discuss studies that investigate
      interventions to limit DC activation, inflammation and HIV transmission. This
      knowledge is essential in the development of novel strategies for effective HIV
      control, including microbicides and pre-exposure prophylaxis.

PMID- 24282127
TI  - Biomimetic multifunctional nanochannels based on the asymmetric wettability of
      heterogeneous nanowire membranes.
AB  - A charged heterogeneous nanowire membrane with asymmetric wettability serves as a
      biomimetic passive channel when the bilayer is hydrophilic; It also functions as
      pH valve based on the hydrophobic CaWO4 layer (contact angle of 145.3+/-0.3) and
      hydrophilic MnO2 layer. Moreover, a reversible ionic rectification is realized in
      the above-mentioned semi-hydrophobic and hydrophilic state with strong acid
      environment or in the complete hydrophobic stage with a moderate discrepancy (CA
      of CaWO4 and MnO2 layer are 141.3+/-0.3 and 157.6+/-2.0, respectively) in near
      neuter condition. 

PMID- 24282128
TI  - Antibody induction therapy for lung transplant recipients.
AB  - BACKGROUND: Lung transplantation has become a valuable and well-accepted
      treatment option for most end-stage lung diseases. Lung transplant recipients are
      at risk of transplanted organ rejection, and life-long immunosuppression is
      necessary. Clear evidence is essential to identify an optimal, safe and effective
      immunosuppressive treatment strategy for lung transplant recipients. Consensus
      has not yet been achieved concerning use of immunosuppressive antibodies against
      T-cells for induction following lung transplantation. OBJECTIVES: We aimed to
      assess the benefits and harms of immunosuppressive T-cell antibody induction with
      ATG, ALG, IL-2RA, alemtuzumab, or muromonab-CD3 for lung transplant recipients.
      SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 4
      March 2013 through contact with the Trials Search Co-ordinator using search terms
      relevant to this review. Studies contained in the Specialised Register are
      identified through search strategies specifically designed for CENTRAL, MEDLINE
      and EMBASE. SELECTION CRITERIA: We included all randomised controlled trials
      (RCTs) that compared immunosuppressive monoclonal and polyclonal T-cell antibody
      induction for lung transplant recipients. An inclusion criterion was that all
      participants must have received the same maintenance immunosuppressive therapy
      within each study. DATA COLLECTION AND ANALYSIS: Three authors extracted data. We
      derived risk ratios (RR) for dichotomous data and mean differences (MD) for
      continuous data with 95% confidence intervals (CI). Methodological risk of bias
      was assessed using the Cochrane risk of bias tool and trial sequential analyses
      were undertaken to assess the risk of random errors (play of chance). MAIN
      RESULTS: Our review included six RCTs (representing a total of 278 adult lung
      transplant recipients) that assessed the use of T-cell antibody induction.
      Evaluation of the included studies found all to be at high risk of bias.We
      conducted comparisons of polyclonal or monoclonal T-cell antibody induction
      versus no induction (3 studies, 140 participants); polyclonal T-cell antibody
      versus no induction (3 studies, 125 participants); interleukin-2 receptor
      antagonists (IL-2RA) versus no induction (1 study, 25 participants); polyclonal T
      cell antibody versus muromonab-CD3 (1 study, 64 participants); and polyclonal T
      cell antibody versus IL-2RA (3 studies, 100 participants). Overall we found no
      significant differences among interventions in terms of mortality, acute
      rejection, adverse effects, infection, pneumonia, cytomegalovirus infection,
      bronchiolitis obliterans syndrome, post-transplantation lymphoproliferative
      disease, or cancer.We found a significant outcome difference in one study that
      compared antithymocyte globulin versus muromonab-CD3 relating to adverse events
      (25/34 (74%) versus 12/30 (40%); RR 1.84, 95% CI 1.13 to 2.98). This suggested
      that antithymocyte globulin increased occurrence of adverse events. However,
      trial sequential analysis found that the required information size had not been
      reached, and the cumulative Z-curve did not cross the trial sequential alpha
      spending monitoring boundaries.None of the studies reported quality of life or
      kidney injury. Trial sequential analyses indicated that none of the meta-analyses
      achieved required information sizes and the cumulative Z-curves did not cross the
      trial sequential alpha-spending monitoring boundaries, nor reached the area of
      futility. AUTHORS' CONCLUSIONS: No clear benefits or harms associated with the
      use of T-cell antibody induction compared with no induction, or when different
      types of T-cell antibodies were compared were identified in this review. Few
      studies were identified that investigated use of antibodies against T-cells for
      induction after lung transplantation, and numbers of participants and outcomes
      were also limited. Assessment of the included studies found that all were at high
      risk of methodological bias.Further RCTs are needed to perform robust assessment
      of the benefits and harms of T-cell antibody induction for lung transplant
      recipients. Future studies should be designed and conducted according to
      methodologies to reduce risks of systematic error (bias) and random error (play
      of chance).

PMID- 24282129
TI  - Testing for measurement invariance with respect to an ordinal variable.
AB  - Researchers are often interested in testing for measurement invariance with
      respect to an ordinal auxiliary variable such as age group, income class, or
      school grade. In a factor-analytic context, these tests are traditionally carried
      out via a likelihood ratio test statistic comparing a model where parameters
      differ across groups to a model where parameters are equal across groups. This
      test neglects the fact that the auxiliary variable is ordinal, and it is also
      known to be overly sensitive at large sample sizes. In this paper, we propose
      test statistics that explicitly account for the ordinality of the auxiliary
      variable, resulting in higher power against "monotonic" violations of measurement
      invariance and lower power against "non-monotonic" ones. The statistics are
      derived from a family of tests based on stochastic processes that have recently
      received attention in the psychometric literature. The statistics are illustrated
      via an application involving real data, and their performance is studied via
      simulation. 

PMID- 24282130
TI  - A note on weighted likelihood and Jeffreys modal estimation of proficiency levels
      in polytomous item response models.
AB  - Warm (in Psychometrika, 54, 427-450, 1989) established the equivalence between
      the so-called Jeffreys modal and the weighted likelihood estimators of
      proficiency level with some dichotomous item response models. The purpose of this
      note is to extend this result to polytomous item response models. First, a
      general condition is derived to ensure the perfect equivalence between these two
      estimators. Second, it is shown that this condition is fulfilled by two broad
      classes of polytomous models including, among others, the partial credit, rating
      scale, graded response, and nominal response models. 

PMID- 24282131
TI  - Sacred populations of Cercopithecus sclateri: analysis of apparent population
      increases from census counts.
AB  - The development of effective conservation and management actions for populations
      of wild species generally requires monitoring programs that provide reliable
      estimates of population size over time. Primate researchers have to date given
      more attention to evaluating techniques for monitoring primates in natural
      habitats compared to populations that occur in villages or urban areas. We
      conducted censuses to estimate the abundance and density of two sacred, village
      dwelling populations (Lagwa and Akpugoeze) of Sclater's monkey (Cercopithecus
      sclateri), a threatened species endemic to southeastern Nigeria, and compared
      these data to previous census results. We recorded population increases in both
      sites: a 66% increase over 41/2 years in Lagwa (from 124 to 206 individuals) at
      an annual rate of 10.2%, and a 29% increase over 4 years in Akpugoeze (from 193
      to 249 individuals) at an annual rate of 5.7%. Mean group size also increased in
      both sites. Density in Lagwa was 24.2 individuals/km(2) , and density in a core
      survey area of Akpugoeze was 36-38 individuals/km(2) . Our results may have been
      affected by monkey ranging and grouping patterns and improved detectability due
      to our revised census technique, which included secondary observers. With further
      work on methodology for censusing populations that occur in human-settled
      environments, techniques can be refined and customized to individual sites for
      more accurate estimates. Our investigation of Sclater's monkey in Lagwa and
      Akpugoeze, two sites critical for conservation of the species, indicated that
      both of these populations have increased, and neither faces immediate risk of
      extirpation. Such population growth, while encouraging, will likely exacerbate
      human-monkey conflict and thus should be understood in terms of potential
      socioeconomic impacts.

PMID- 24282132
TI  - Susceptibility status of Aedes aegypti (L.) (Diptera: Culicidae) to temephos in
      Venezuela.
AB  - BACKGROUND: Temephos is an insecticide widely used in Venezuela to control the
      proliferation of the larvae of Aedes aegypti (L.), the principal vector of dengue
      virus. The aim of this study was to identify the susceptibility to temephos of
      Ae. aegypti in four locations in western Venezuela: Lara, Tres Esquinas, Urena
      and Pampanito. Larval bioassays were conducted on samples collected in 2008 and
      2010, and the levels of alpha- and beta-esterases, mixed-function oxidases,
      glutathione-S-transferase and insensitive acethyl cholinesterase were determined.
      RESULTS: Larval populations from western Venezuela obtained during 2008 and 2010
      were found to be susceptible to temephos, with low resistance ratios and without
      overexpression of enzymes. CONCLUSIONS: The low RR values reveal the
      effectiveness of temephos in controlling the larval populations of Ae. aegypti.
      Control strategies must be vigorously monitored to maintain the susceptibility to
      temephos of these populations of Ae. aegypti.

PMID- 24282133
TI  - Combining on-chip synthesis of a focused combinatorial library with computational
      target prediction reveals imidazopyridine GPCR ligands.
AB  - Using the example of the Ugi three-component reaction we report a fast and
      efficient microfluidic-assisted entry into the imidazopyridine scaffold, where
      building block prioritization was coupled to a new computational method for
      predicting ligand-target associations. We identified an innovative GPCR
      modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and
      adrenergic alpha1A/B receptor antagonists. Our results suggest the tight
      integration of microfluidics-assisted synthesis with computer-based target
      prediction as a viable approach to rapidly generate bioactivity-focused
      combinatorial compound libraries with high success rates. 

PMID- 24282134
TI  - Effects of memory instruction on attention and information processing: Further
      investigation of inhibition of return in item-method directed forgetting.
AB  - In the item-method directed-forgetting paradigm, the magnitude of inhibition of
      return (IOR) is larger after an instruction to forget (F) than after an
      instruction to remember (R). In the present experiments, we further investigated
      this increased magnitude of IOR after F as compared to R memory instructions
      (dubbed the F > R IOR difference), in order to understand both the consequences
      for information processing and the purpose of the differential withdrawal of
      attention that results in this difference. Words were presented in one of four
      peripheral locations, followed by either an F or an R memory instruction. Then, a
      target appeared in either the same location as the previous word or one of the
      other locations. The results showed that the F > R IOR difference cannot be
      explained by attentional momentum (Exp. 1), that the spatial compatibility of the
      response options with target locations is not necessary for the F > R IOR
      difference to emerge (Exp. 2), and that the F > R IOR difference is location
      specific rather than response-specific (Exp. 3). These results are consistent
      with the view that F > R IOR represents a bias against responding to information
      emanating from an unreliable source (Taylor & Fawcett, 2011).

PMID- 24282135
TI  - Preparation and application of immobilised ionic liquid in solid-phase extraction
      for determination of trace acrylamide in food samples coupled with high
      performance liquid chromatography.
AB  - BACKGROUND: Acrylamide has attracted worldwide concerns because of its
      demonstrated neurotoxicity, genetoxicity and reproductive-development toxicity.
      It is necessary to control acrylamide production during food processing and
      protect human health. RESULTS: In this study, a functionalised material was
      synthesised by immobilising an ionic liquid onto an activated silica gel surface.
      The adsorption ability of the material towards acrylamide was evaluated, and the
      results showed that it had high adsorption capacity. Scatchard analysis indicated
      that the binding sites in the prepared material had two distinct groups (high and
      low affinity binding sites). The saturated adsorption capacity (Q(max,1)) was 7.9
      mg g(-1) due to the high affinity binding sites, and another saturated adsorption
      capacity (Q(max,2)) was 2.3 mg g(-1) due to the low affinity binding sites. This
      prepared material also offered fast kinetics for adsorption of the acrylamide.
      Using this material as sorbent, a method of solid-phase extraction coupled with
      high-performance liquid chromatography (SPE-HPLC) for analysis of acrylamide in
      foods was developed. Under optimal conditions, the limit of detection (S/N = 3)
      of this method for acrylamide was 2.1 ug kg(-1), and the RSD for five replicate
      extractions of 50 MUL(-1) acrylamide was 4.5%. The blank potato and bread crumb
      samples spiked with acrylamide at different levels of 10.0 and 15.0 ug kg(-1)
      were extracted and determined respectively by this developed method, and
      recoveries ranging from 83.0% to 89.1% were obtained. Finally, this method was
      applied to quantitative detection of acrylamide in bread crust and cracker
      samples. CONCLUSION: With high sensitivity and pre-treatment simplicity, this SPE
      HPLC method could provide a new tool for the rapid determination of acrylamide in
      the food samples.

PMID- 24282136
TI  - Five-degree, 10-degree, and 20-degree reverse Trendelenburg position during
      functional endoscopic sinus surgery: a double-blind randomized controlled trial.
AB  - BACKGROUND: Using the reverse Trendelenburg position (RTP) during functional
      endoscopic sinus surgery (FESS) is a safe, simple, and cost-free method that has
      been found to reduce intraoperative blood loss. However, the critical angle of
      RTP that produces the least amount of bleeding without compromising surgical
      technique and safety remains unanswered. The objective of this study was to
      assess the effects of 5-degree, 10-degree, and 20-degree RTP (5-RTP, 10-RTP, and
      20-RTP, respectively) on intraoperative bleeding during FESS. METHODS: This
      double-blind randomized controlled trial involved 75 patients with chronic
      rhinosinusitis (CRS) with and without nasal polyposis undergoing FESS. Twenty
      five patients were enrolled into each group: 5-RTP, 10-RTP, and 20-RTP. Boezaart
      endoscopic field-of-view score (BS), total blood loss (TBL), mean arterial blood
      pressure (MABP), operating time, and blood loss per minute were recorded. An
      intention-to-treat analysis was used, with a Bonferroni adjustment for multiple
      comparisons. RESULTS: Intervention groups were comparable in age, sex, nasal
      polyposis, and disease severity. Mean values of BS and TBL were as follows: 5-RTP
      (2.0, 231 mL), 10-RTP (1.8, 230 mL), and 20-RTP (1.4, 135 mL). The differences in
      means were significant for BS (p < 0.01) and TBL (p = 0.03). There was no
      significant difference in MABP (p = 0.85), operating time (p = 0.10), or blood
      loss per minute (p = 0.11) between the 3 groups. Pairwise comparison between 5
      RTP vs 20-RTP found significant difference in BS (p < 0.01) but not TBL (p =
      0.04). Significance was not found in similar comparisons of 10-RTP vs 20-RTP and
      5-RTP vs 10-RTP (p > 0.03). CONCLUSION: FESS in 20-RTP produced the best BS and
      lowest blood loss without compromising surgical technique.

PMID- 24282137
TI  - Adapting non-local means of de-noising in intraoperative magnetic resonance
      imaging for brain tumor surgery.
AB  - In image-guided brain tumor surgery, intraoperative magnetic resonance imaging
      (iMRI) is a powerful tool for updating navigational information after brain
      shift, controlling the resection of brain tumors, and evaluating intraoperative
      complications. Low-field iMRI scans occasionally generate a lot of noise, the
      reason for which is yet to be determined. This noise adversely affects the
      neurosurgeons' interpretations. In this study, in order to improve the image
      quality of iMR images, we optimized and adapted an unbiased non-local means
      (UNLM) filter to iMR images. This noise appears to occur at a specific frequency
      encoding band. In order to adapt the UNLM filter to the noise, we improved the
      UNLM, so that de-noising can be performed at different noise levels that occur at
      different frequency-encoding bands. As a result, clinical iMR images can be de
      noised adequately while preserving crucial information, such as edges. The UNLM
      filter preserved the edges more clearly than did other classical filters attached
      to an anisotropic diffusion filter. In addition, UNLM de-noising can improve the
      signal-to-noise ratio of clinical iMR images by more than 2 times (p < 0.01).
      Although the computational time of the UNLM processing is very long, post
      processing of UNLM filter images, for which the parameters were optimized, can be
      performed during other MRI scans. Therefore, The UNLM filter was more effective
      than increasing the number of signal averages. The iMR image quality was improved
      without extension of the MR scanning time. UNLM de-noising in post-processing is
      expected to improve the diagnosability of low-field iMR images. 

PMID- 24282138
TI  - Why is firefly oxyluciferin a notoriously labile substance?
AB  - The chemistry of firefly bioluminescence is important for numerous applications
      in biochemistry and analytical chemistry. The emitter of this bioluminescent
      system, firefly oxyluciferin, is difficult to handle. The cause of its lability
      was clarified while its synthesis was reinvestigated. A side product was
      identified and characterized by NMR spectroscopy and X-ray crystallography. The
      reason for the lability of oxyluciferin is now ascribed to autodimerization of
      the coexisting enol and keto forms in a Mannich-type reaction. 

PMID- 24282139
TI  - Sponge-like nickel and nickel nitride structures for catalytic applications.
AB  - A safe and simple method to fabricate air-stable nickel nitride and nickel
      embedded in carbon and nitrogen matrix, with high surface area for catalytic
      applications, is presented. The new synthesis employs molten inorganic salts as
      the reaction media. The use of salt melt opens new possibilities for safe,
      simple, and cheap synthesis of metal nitrides and metals for energy-related
      applications. 

PMID- 24282140
TI  - Lake Louise mutation detection meeting 2013: clinical translation of next
      generation sequencing requires optimization of workflows and interpretation of
      variants.
AB  - With the exponential reduction of the cost of next-generation sequencing (NGS),
      it is no longer the generation of data but the analysis and interpretation of
      massive amounts of sequencing data that are seen as key challenges for the
      effective integration of these technologies into clinical practice. Clinical
      geneticists, informaticians, and scientists from 17 countries gathered for the
      12th International Symposium on Mutation in the Genome at the Fairmont Chateau
      Lake Louise (Canada) to discuss technological advances and applications of NGS
      and consider possible approaches to the challenges of clinical translation. Here,
      we provide an overview of the main themes of the meeting that included
      development of innovative solutions for variant sharing, tools and resources for
      NGS analysis, novel technology and methodology development, NGS-based discovery
      of disease pathogenesis, development of multigene NGS sequencing panels for
      clinical use, exploring diagnostic utility of whole-exome and whole-genome
      sequencing, and, finally, integration of genomic sequencing into the clinic. 

PMID- 24282141
TI  - The effect of energetic and psychosocial stressors on glucocorticoids in mantled
      howler monkeys (Alouatta palliata).
AB  - The proximate causes of variation in glucocorticoids (GCs) of many free-ranging
      primates are still unclear, and in some cases, the available evidence is
      contradictory. Such is the case of mantled howler monkeys. In the present study,
      we tested whether variation in GC levels in this species could be predicted by
      energetic challenges or by psychosocial stressors. We focused on two groups
      living in Los Tuxtlas (Veracruz, Mexico) that differed in a number of parameters
      including: group size, habitat size, number of groups, and solitary males within
      the same habitat. Furthermore, one of the groups experienced changes in
      composition during our observations. From March to December 2009 we determined
      food availability in each group's habitat, studied the behavior of all adult
      individuals (N = 17), including, feeding, time budgets, ranging, and social
      interactions (N = 426.6 h), and measured weekly GCs in fecal samples (N = 160
      individual/weeks) of both females and males. We found that participation in
      agonistic interactions, which were more frequent in the group that lived in the
      smaller habitat, was associated with increased weekly GCs, particularly in
      pregnant and lactating females. During the dry season weekly GCs were also higher
      in the group that lived in the smaller habitat. Although in this group
      individuals significantly increased travel time during the dry season, weekly GC
      levels were unrelated to time-budgets or ranging distances, contrasting with
      previous findings on mantled howler monkeys' GC response. We found no evidence
      that weekly variation in GC levels between groups resulted from differences in
      food availability. Our results indicate that mantled howler monkey GC levels
      respond to the effects of agonism, reproductive state, and the influence of a
      seasonal stressor, which may be attributable to anthropogenic disturbance. We
      conclude that psychosocial stressors affect the GC response of mantled howler
      monkeys, and that this response is modulated by reproductive state.

PMID- 24282142
TI  - Eisenbergiella tayi gen. nov., sp. nov., isolated from human blood.
AB  - A catalase-positive, rod-shaped, non-proteolytic, non-motile, anaerobic bacterial
      strain, designated B086562(T), was isolated from a blood culture of an 84-year
      old male patient in Israel. According to 16S rRNA gene sequence phylogeny, this
      strain has no known close relatives among recognized bacteria but should be
      placed within the family Lachnospiraceae. The most closely related recognized
      bacteria were from the 'Clostridium clostridioforme group': C. clostridioforme
      (92.4%) and Clostridium bolteae (92.3%). The isolate produced butyrate, lactate,
      acetate and succinate as major metabolic end products. The major fatty acids were
      C16:0 and C18:1 cis 9 DMA and the DNA G+C content was 46.0 mol%. On the basis of
      the phenotypic properties and phylogenetic distinctiveness, the blood isolate
      represents a novel species of a new genus in the family Lachnospiraceae, for
      which the name Eisenbergiella tayi gen. nov., sp. nov. is proposed. The type
      strain of Eisenbergiella tayi is B086562(T) ( = LMG 27400(T) = DSM 26961(T) =
      ATCC BAA-2558(T)).

PMID- 24282143
TI  - Chemotherapy versus best supportive care for extensive small cell lung cancer.
AB  - BACKGROUND: Combination chemotherapy has been the mainstay of treatment for
      extensive stage small celI lung cancer (SCLC) over the last 30 years, even though
      it only gives a short prolongation in median survival time. The main goal for
      these patients should be palliation with the aim of improving their quality of
      life. OBJECTIVES: To determine the effectiveness of first-line chemotherapy
      versus placebo or best supportive care (BSC) in prolonging survival in patients
      with extensive SCLC at diagnosis and the effectiveness of second-line
      chemotherapy at relapse or progression after first-line chemotherapy compared
      with BSC or placebo in prolonging survival in patients with extensive SCLC; as
      well as to evaluate the adverse events of treatment and the quality of life of
      patients. SEARCH METHODS: This is the second update of the review. MEDLINE (1966
      to October 2013), EMBASE (1974 to October 2013), and the Cochrane Central
      Register of Controlled Trials (CENTRAL) (2012, Issue 3) were searched. Experts in
      the field were contacted. SELECTION CRITERIA: Phase III randomised controlled
      trials in which any chemotherapy treatment was compared with  placebo or BSC in
      patients with extensive SCLC, as first-line or second-line therapy at relapse.
      DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and
      assessed study quality. We resolved disagreements by discussion. Additional
      information was obtained from one study author. MAIN RESULTS: Two studies of
      unclear risk of bias were included for first-line chemotherapy. A total of 88 men
      under 70 years with good performance status were randomised to receive either
      supportive care, placebo infusion or ifosfamide. Ifosfamide gave an extra mean
      survival of 78.5 days compared with supportive care or placebo infusion. Partial
      tumour response was greater with the active treatment. Toxicity was only seen in
      the chemotherapy group and quality of life was only assessed at the beginning of
      treatment. The quality of the evidence for overall survival and adverse effects
      was very low.Three studies of moderate risk of bias were included for second-line
      chemotherapy at relapse (one identified in the last search). A total of 932 men
      and women under 75 years and any performance status were randomised to receive
      either methotrexate-doxorubicin, topotecan, or picoplatin versus symptomatic
      treatment or BSC. The methotrexate-doxorubicin treatment gave a median survival
      of 63 days longer than in the symptomatic-treatment group for patients allocated
      to receive four cycles of first-line chemotherapy, and 21 days longer for
      patients allocated to receive eight cycles of first-line chemotherapy.Treatment
      with topotecan gave a median survival of 84 days longer than in the BSC group
      (log-rank P = 0.01). The adjusted hazard ratio (HR) for overall survival was 0.61
      (95% CI 0.43 to 0.87). Treatment with picoplatin gave a median survival time of
      six days longer than BSC (HR 0.817, 95% CI 0.65 to 1.03, P = 0.0895). A meta
      analysis of topotecan and picoplatin gave a HR of 0.73 (95% CI 0.55 to 0.96, P =
      0.03; low-quality evidence).Partial or complete response in the methotrexate
      doxorubicin group was 22.3%. Five patients (7%, 95% CI 2.33 to 15.67) showed a
      partial response with topotecan. No data were provided about tumour response in
      the picoplatin study. Toxicity was worst in the chemotherapy group (moderate
      quality evidence). Quality of life was better in the topotecan group and was not
      measured in the methotrexate-doxorubicin and picoplatin studies (low-quality
      evidence). AUTHORS' CONCLUSIONS: Two small RCTs from the 1970s suggest that first
      line chemotherapeutic treatment (based on ifosfamide) may provide a small
      survival benefit (less than three months) in comparison with supportive care or
      placebo infusion in patients with advanced SCLC. However platinum-based
      combination chemotherapy regimens have been shown to increase complete response
      rates when compared to non-platinum chemotherapy regimens with no significant
      difference in survival, and so these are currently the standard first-line
      treatment for patients with SCLC.Second-line chemotherapy at relapse or
      progression may prolong survival for some weeks in relation to BSC. Nevertheless,
      the impact of first-line chemotherapy on quality of life, older patients, women
      and patients with poor prognosis is unknown and the benefits of second-line
      chemotherapy are also unclear for older people. Globally, the evidence on which
      these conclusions are based is very scarce and of uncertain or low quality, which
      calls for well-designed, controlled trials to further evaluate the trade-offs
      between benefits and risks of different chemotherapeutic schedules in patients
      with advanced SCLC.

PMID- 24282144
TI  - Does Gender Moderate the Relations Between Externalizing Behavior and Key
      Emergent Literacy Abilities? Evidence From a Longitudinal Study.
AB  - OBJECTIVE: There is a significant negative relation between externalizing
      behavior and emergent literacy skills among preschool children. METHOD: The
      purpose of this study was to examine the impact of gender on the predictive
      relation of externalizing behavior and emergent literacy in a group of 178
      preschool children (mean age = 48.50 months, SD = 3.66; 48% boys). RESULTS:
      Externalizing behaviors predicted emergent literacy over time. Distinct patterns
      of predictive associations dependent on gender were found. Girls with higher
      levels of externalizing behaviors experienced less change in their vocabulary
      skills compared with the vocabulary change shown by girls with lower levels of
      these problem behaviors. CONCLUSION: The results suggest that early
      identification programs that include externalizing behavior problems and their
      relation with emergent literacy development should account for potential gender
      differences. A theoretical framework in which girls with behavior problems
      receive less opportunity for vocabulary acquisition is presented.

PMID- 24282145
TI  - Plant resistance to aphid feeding: behavioral, physiological, genetic and
      molecular cues regulate aphid host selection and feeding.
AB  - Aphids damage major world food and fiber crops through direct feeding and
      transmission of plant viruses. Fortunately, the development of many aphid
      resistant crop plants has provided both ecological and economic benefits to food
      production. Plant characters governing aphid host selection often dictate
      eventual plant resistance or susceptibility to aphid herbivory, and these
      phenotypic characters have been successfully used to map aphid resistance genes.
      Aphid resistance is often inherited as a dominant trait, but is also polygenic
      and inherited as recessive or incompletely dominant traits. Most aphid-resistant
      cultivars exhibit constitutively expressed defenses, but some cultivars exhibit
      dramatic aphid-induced responses, resulting in the overexpression of large
      ensembles of putative aphid resistance genes. Two aphid resistance genes have
      been cloned. Mi-1.2, an NBS-LRR gene from wild tomato, confers resistance to
      potato aphid and three Meloidogyne root-knot nematode species, and Vat, an NBS
      LRR gene from melon, controls resistance to the cotton/melon aphid and to some
      viruses. Virulence to aphid resistance genes of plants occurs in 17 aphid species
      -more than half of all arthropod biotypes demonstrating virulence. The continual
      appearance of aphid virulence underscores the need to identify new sources of
      resistance of diverse sequence and function in order to delay or prevent biotype
      development.

PMID- 24282146
TI  - Effect of thermal treatments on anti-nutritional factors and antioxidant
      capabilities in yellow soybeans and green-cotyledon small black soybeans.
AB  - BACKGROUND: The effects of different thermal processes on the anti-nutritional
      factors (tannins, phytic acids and trypsin inhibitors) and antioxidant capacity
      of yellow soybeans (YS) and green-cotyledon small black soybeans (GCSBS) were
      investigated. The soybean samples were subjected to roasting, microwaving and
      boiling as the thermal treatments. RESULTS: Sixty-minute boiling was most
      effective for eliminating the tannins in both YS and GCSBS, and also resulted in
      the maximal reduction of phytic acids. Trypsin inhibitors were most effectively
      reduced (76.92-97.91%) by microwaving, and boiling was least favourable for
      retaining total phenolic content. The total flavonoid content was significantly
      (P < 0.05) decreased by all thermal processes, and particularly by employing 60
      min boiling. The total anthocyanin content of GCSBS was higher than that of YS,
      but significantly declined upon boiling (P < 0.05). Roasting did not
      significantly affect the DPPH free radical scavenging activity of GCSBS (P >
      0.05). Microwaving increased the FRAP (ferric reducing antioxidant power) of
      GCSBS up to 6.07%. CONCLUSION: Our raw GCSBS possesses much better antioxidant
      capacity than raw YS. Microwaving resulted in a substantial reduction of the
      trypsin inhibitors of our soybean samples. Dry thermal treatments caused slight
      increase of FRAP in GCSBS.

PMID- 24282147
TI  - New insights into the pathogenesis of cystic fibrosis sinusitis.
AB  - BACKGROUND: People with cystic fibrosis (CF) sinus disease have developmental
      sinus abnormalities with airway bacterial infection, inflammation, impaired
      mucociliary clearance and thick obstructive mucus. The pathophysiology of airway
      disease in CF is not completely understood, and current treatments in CF sinus
      disease ameliorate symptoms but do not provide a cure. METHODS: This manuscript
      reviews the history of CF, its manifestations in sinus disease, and the potential
      impact and relationship of CF on the upper and lower airway. RESULTS: There is
      increasing evidence that CF sinus disease may affect CF lung disease, the most
      common cause of mortality in CF. We have been limited in treating the symptoms of
      advanced CF sinus disease with our current therapies. CONCLUSIONS: Recent
      discoveries in the pathophysiology of CF using the CF porcine animal model and
      exciting treatments that address the primary gene defect that may translate into
      improved outcomes in CF and non-CF sinusitis in humans.

PMID- 24282148
TI  - Threat-related attentional bias in anorexia nervosa.
AB  - OBJECTIVE: Attentional bias (AB) modification treatment targeting general or
      social anxiety has been recently highlighted as a potential novel approach for
      the treatment of anorexia nervosa (AN). The purpose of this study was to examine
      threat-related AB in patients with ANand healthy control participants (HC) and
      the relationship between AB and eating disorder and other psychopathology.
      METHOD: Forty-nine female outpatients with AN or Eating Disorder Not Otherwise
      Specified, Anorexia Type (EDNOS-AN), and 44 female HC completed a dot-probe task
      with threat words and a range of self-report measures assessing eating disorder
      symptoms and other psychopathology. RESULTS: There was no evidence for a
      differential threat-related AB in AN patients despite elevated anxiety in this
      group. The AB-index, a parameter of the magnitude of attention allocation when
      two competing stimuli are presented, did not correlate with any of the self
      report measures. However, patients with AN responded significantly more slowly to
      the probe as compared to controls, regardless of the valence or position of the
      stimuli. DISCUSSION: The results suggest that the AB in AN patients may be
      specific to eating disorder-relevant anxieties.

PMID- 24282149
TI  - Targeted knock-in of the polymorphism rs61764370 does not affect KRAS expression
      but reduces let-7 levels.
AB  - Understanding the role of single-nucleotide polymorphisms (SNPs) in the
      pathological process represents a unique experimental challenge especially when
      the variants occur outside of coding regions. The noncoding SNP rs61764370
      located in the 3'-untranslated region of Kirsten rat sarcoma viral oncogene
      homolog (KRAS) has been implicated as a risk factor for the development of cancer
      and the response to targeted therapies. This cancer-associated variant is thought
      to affect the binding of the microRNA let-7, which allegedly modulates KRAS
      expression. Using site-specific homologous recombination, we inserted the
      rs61764370:T>G KRAS gene variant in the colorectal cancer cell line SW48 (SW48
      +SNP) and assessed the cellular and biochemical phenotype. We observed a
      significant increase in cellular proliferation, as well as a reduction in the
      levels of the microRNA let-7a, let-7b, and let-7c. Transcriptional and
      biochemical analysis showed no concomitant change in the KRAS protein expression
      or modulation of the downstream mitogen activated kinase or PI3K/AKT signaling.
      These results suggest that the cancer-associated rs61764370 variant exerts a
      biological effect not through transcriptional modulation of KRAS but rather by
      tuning the expression of the microRNA let-7. 

PMID- 24282150
TI  - A dendritic thioester hydrogel based on thiol-thioester exchange as a dissolvable
      sealant system for wound closure.

PMID- 24282151
TI  - Twisted aligned carbon nanotube/silicon composite fiber anode for flexible wire
      shaped lithium-ion battery.
AB  - Twisted, aligned carbon nanotube/silicon composite fibers with remarkable
      mechanical and electronic properties are designed to develop novel flexible
      lithium-ion batteries with a high cyclic stability. The core-sheath architecture
      and the aligned structure of the composite nanotube offer excellent combined
      properties. 

PMID- 24282152
TI  - Ontogeny of material stiffness heterogeneity in the macaque mandibular corpus.
AB  - Evidence is accumulating that bone material stiffness increases during ontogeny,
      and the role of elastic modulus in conditioning attributes of strength and
      toughness is therefore a focus of ongoing investigation. Developmental changes in
      structural properties of the primate mandible have been documented, but
      comparatively little is known about changes in material heterogeneity and their
      impact on biomechanical behavior. We examine a cross-sectional sample of Macaca
      fascicularis (N = 14) to investigate a series of hypotheses that collectively
      evaluate whether the patterning of material stiffness (elastic modulus)
      heterogeneity in the mandible differs among juvenile, subadult and adult
      individuals. Because differences in age-related activity patterns are known to
      influence bone stiffness and strength, these data are potentially useful for
      understanding the relationship between feeding behavior on the one hand and
      material and structural properties of the mandible on the other. Elastic modulus
      is shown to be spatially dependent regardless of age, with this dependence being
      explicable primarily by differences in alveolar versus basal cortical bone.
      Elastic modulus does not differ consistently between buccal and lingual cortical
      plates, despite likely differences in the biomechanical milieu of these regions.
      Since we found only weak support for the hypothesis that the spatial patterning
      of heterogeneity becomes more predictable with age, accumulated load history may
      not account for regional differences in bone material properties in mature
      individuals with respect to the mandibular corpus.

PMID- 24282153
TI  - Dissipation rate of thiacloprid and its control effect against Bemisia tabaci in
      greenhouse tomato after soil application.
AB  - BACKGROUND: Thiacloprid is a chloronicotinyl insecticide that is quite effective
      against sucking insects. In this study, when thiacloprid was applied at two
      different rates (normal rate 15 kg ha(-1) , double rate 30 kg ha(-1) ), the
      systemic distribution and residue of thiacloprid as well as its control effect
      against whitefly (Bemisia tabaci) were investigated in greenhouse tomato after
      soil application. RESULTS: The results showed that thiacloprid was present in the
      tomato leaves until day 25, and then its amount was less than 0.005 mg kg(-1) and
      could not be detected. Thiacloprid residue in the tomato stems basically remained
      at a stable low level throughout the experimental period. Thiacloprid in soil had
      half-lives of 11.8 and 12.5 days for the normal treatment and the double
      treatment respectively. The control efficiency of whiteflies was about 90% from
      day 1 to day 10. This was followed by a slow decline, but efficiency was still
      higher than 50% until day 21. In addition, no significant differences were noted
      in the control effect of thiacloprid on whiteflies between the two different
      rates. CONCLUSION: Soil application of thiacloprid at the normal rate can
      effectively control whiteflies, with high efficiency and long persistence.

PMID- 24282154
TI  - What impedes and what facilitates a quality improvement project for older
      hospitalized patients?
AB  - OBJECTIVE: To gain insight into which factors impede, and which facilitate, the
      implementation of a complex multi-component improvement initiative in
      hospitalized older patients. DESIGN: A qualitative study based on semi-structured
      interviews. The three dimensions of Pettigrew and Whipp's theoretical framework,
      namely, Process, Content and Context, were used to undertake a structured data
      analysis. SETTING: The study was conducted in 19 Dutch hospitals implementing the
      Frail Elderly Project. PARTICIPANTS: Sixty-five members of staff, including
      physicians, nurses and members of the policy team. INTERVENTION: The Frail
      Elderly Project, a Dutch quality improvement program, aims to decrease adverse
      events in frail older hospitalized people by implementing screening instruments
      and interventions targeting delirium, falls, malnutrition and physical
      impairment. MAIN OUTCOME MEASURES: The management of the process of
      implementation, participants' opinions of the program elements and contextual
      factors which influence the implementation. RESULTS: Barriers to implementation
      included two process factors (insufficient involvement of clinicians and lack of
      time), two content factors (having divergent objectives and concerns about
      recommended program elements) and two contextual factors (a lack of knowledge of
      delirium and minimal insight into the purposes and effects of the program).
      Facilitating factors included one process factor (leadership), one content factor
      (flexibility in choosing methods) and two contextual factors (the program's
      guidance and the use of digital patient records). CONCLUSION: We identified the
      barriers and the factors which facilitate implementing complex multi-component
      improvement programs concerning care for older patients. These barriers must be
      resolved in future improvement programs in order to ensure successful
      implementation.

PMID- 24282155
TI  - Development and validation of a high-content bimolecular fluorescence
      complementation assay for small-molecule inhibitors of HIV-1 Nef dimerization.
AB  - Nef is a human immunodeficiency virus 1 (HIV-1) accessory factor essential for
      viral pathogenesis and AIDS progression. Many Nef functions require dimerization,
      and small molecules that block Nef dimerization may represent antiretroviral drug
      leads. Here we describe a cell-based assay for Nef dimerization inhibitors based
      on bimolecular fluorescence complementation (BiFC). Nef was fused to
      nonfluorescent, complementary fragments of yellow fluorescent protein (YFP) and
      coexpressed in the same cell population. Dimerization of Nef resulted in
      juxtaposition of the YFP fragments and reconstitution of the fluorophore. For
      automation, the Nef-YFP fusion proteins plus a monomeric red fluorescent protein
      (mRFP) reporter were expressed from a single vector, separated by picornavirus
      "2A" linker peptides to permit equivalent translation of all three proteins.
      Validation studies revealed a critical role for gating on the mRFP-positive
      subpopulation of transfected cells, as well as use of the mRFP signal to
      normalize the Nef-BiFC signal. Nef-BiFC/mRFP ratios resulting from cells
      expressing wild-type versus dimerization-defective Nef were very clearly
      separated, with Z factors consistently in the 0.6 to 0.7 range. A fully automated
      pilot screen of the National Cancer Institute Diversity Set III identified
      several hit compounds that reproducibly blocked Nef dimerization in the low
      micromolar range. This BiFC-based assay has the potential to identify cell-active
      small molecules that directly interfere with Nef dimerization and function. 

PMID- 24282156
TI  - Effects of ischaemic post-conditioning on the early and late testicular damage
      after experimental testis ischaemia-reperfusion.
AB  - Ischaemic post-conditioning (IPostC) might represent an innovative surgical
      approach to protect organs from ischaemia and reperfusion (I/R) injury. We
      investigated the molecular mechanisms underlying the contrasting effects of
      IPostC on the early and late damage induced by testicular I/R injury. Testis I/R
      was induced by occluding the right testicular vessels using a clip. Male rats
      were divided into the following groups: sham, I/R and I/R + IPostC. In the I/R
      group, the clip was removed after 60 min of ischaemia, and reperfusion was
      allowed for 30 min, 1 and 30 days. In the I/R + IPostC group, three cycles of 30
      sec reperfusion and 30-sec ischaemia were performed after 60 min of ischaemia and
      then reperfusion followed up for 30 min, 1 and 30 days. Following 30-min
      reperfusion, there was an increase in mitogen-activated protein kinases (MAPKs)
      in I/R rats; after 1 day of reperfusion, interleukin-6, tumour necrosis factor
      alpha and nuclear factor-kappaB (NF-kappaB) expression were significantly
      increased; IkappaB-alpha expression reduced; and a marked damage in both testes
      was observed. IPostC inhibited MAPKs, cytokines and NF-kappaB expression,
      augmented IkappaB-alpha expression and decreased histological damage in testes
      subjected to I/R. After 30 days of reperfusion, I/R injury activated the
      apoptosis machinery, caused severe histological damage and reduced spermatogenic
      activity. By contrast, IPostC did not modify the apoptotic markers, the
      histological alterations as well as spermatogenic activity following 30 days of
      reperfusion. Our data demonstrate that IPostC protects the testis from the early
      damage induced by I/R injury, but it does not protect against the late damage. 

PMID- 24282157
TI  - Bulimia nervosa-nonpurging subtype: closer to the bulimia nervosa-purging subtype
      or to binge eating disorder?
AB  - OBJECTIVE: DSM-5 has dropped subtyping of bulimia nervosa (BN), opting to
      continue inclusion of the somewhat contentious diagnosis of BN-nonpurging subtype
      (BN-NP) within a broad BN category. Some contend however that BN-NP is more like
      binge eating disorder (BED) than BN-P. This study examines clinical
      characteristics, eating disorder symptomatology, and Axis I comorbidity in BN-NP,
      BN-P, and BED groups to establish whether BN-NP more closely resembles BN-P or
      BED. METHOD: Women with BN-P (n = 29), BN-NP (n = 29), and BED (n = 54) were
      assessed at baseline in an outpatient psychotherapy trial for those with binge
      eating. Measures included the Structured Clinical Interviews for DSM-IV, Eating
      Disorder Examination, and Eating Disorder Inventory-2. RESULTS: The BN-NP subtype
      had BMIs between those with BN-P and BED. Both BN subtypes had higher Restraint
      and Drive for Thinness scores than BED. Body Dissatisfaction was highest in BN-NP
      and predicted BN-NP compared to BN-P. Higher Restraint and lower BMI predicted BN
      NP relative to BED. BN-NP resembled BED with higher lifetime BMIs; and weight
      loss clinic than eating disorder clinic attendances relative to the BN-P subtype.
      Psychiatric comorbidity was comparable except for higher lifetime cannabis use
      disorder in the BN-NP than BN-P subtype DISCUSSION: These results suggest that BN
      NP sits between BN-P and BED however the high distress driving inappropriate
      compensatory behaviors in BN-P requires specialist eating disorder treatment.
      These results support retaining the BN-NP group within the BN category. Further
      research is needed to determine whether there are meaningful differences in
      outcome over follow-up.

PMID- 24282158
TI  - Starch nanocrystals as particle stabilisers of oil-in-water emulsions.
AB  - BACKGROUND: As an environmentally benign particle emulsifier, starch nanocrystal
      (SNC) has attracted considerable attention. By submitting waxy maize starch to
      acid below the gelatinisation temperature of starch, nanoscale crystalline
      residues, which are SNCs, were separated from starch granules by hydrolysing
      amorphous regions. The SNC could be used as a particle emulsifier to stabilise
      emulsions. RESULTS: The SNC could adsorb at the oil-water interface to stabilise
      oil-in-water emulsions with high stability to coalescence. The creaming of
      emulsions occurred after homogenisation but decreased with increasing SNC
      content, which was mainly due to the formation of an inter-particle network in
      the emulsions. Because of the amount of sulfuric groups at the surface, the SNC
      was negatively charged. Therefore, at low pH values or high salt content the
      electrostatic repulsion of the SNC was reduced, which further caused droplet
      aggregation and an increase in size of the particles in the emulsions stabilised
      by the SNC. CONCLUSION: The SNC was an efficient particle emulsifier for
      preparing Pickering emulsions. The size of emulsions stabilised by the SNC could
      be tailored by changing the pH value or salt concentration.

PMID- 24282159
TI  - Enhanced sensitivity for detection of low-level germline mosaic RB1 mutations in
      sporadic retinoblastoma cases using deep semiconductor sequencing.
AB  - Sporadic retinoblastoma (RB) is caused by de novo mutations in the RB1 gene.
      Often, these mutations are present as mosaic mutations that cannot be detected by
      Sanger sequencing. Next-generation deep sequencing allows unambiguous detection
      of the mosaic mutations in lymphocyte DNA. Deep sequencing of the RB1 gene on
      lymphocyte DNA from 20 bilateral and 70 unilateral RB cases was performed, where
      Sanger sequencing excluded the presence of mutations. The individual exons of the
      RB1 gene from each sample were amplified, pooled, ligated to barcoded adapters,
      and sequenced using semiconductor sequencing on an Ion Torrent Personal Genome
      Machine. Six low-level mosaic mutations were identified in bilateral RB and four
      in unilateral RB cases. The incidence of low-level mosaic mutation was estimated
      to be 30% and 6%, respectively, in sporadic bilateral and unilateral RB cases,
      previously classified as mutation negative. The frequency of point mutations
      detectable in lymphocyte DNA increased from 96% to 97% for bilateral RB and from
      13% to 18% for unilateral RB. The use of deep sequencing technology increased the
      sensitivity of the detection of low-level germline mosaic mutations in the RB1
      gene. This finding has significant implications for improved clinical diagnosis,
      genetic counseling, surveillance, and management of RB. 

PMID- 24282160
TI  - Single-electron-transfer-induced coupling of arylzinc reagents with aryl and
      alkenyl halides.
AB  - Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard
      reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl
      halides without the aid of transition-metal catalysis to give biaryls and styrene
      derivatives, respectively. In this context, we have already reported the
      corresponding reaction using aryl Grignard reagents instead of arylzinc reagents.
      Compared with the Grignard cross-coupling, the present reaction features high
      functional-group tolerance, whereby electrophilic groups such as alkoxycarbonyl
      and cyano groups are compatible as substituents on both the arylzinc reagents and
      the aryl halides. Aryl halides receive a single electron and thereby become
      activated as the corresponding anion radicals, which react with arylzinc
      reagents, thus leading to the cross-coupling products. 

PMID- 24282161
TI  - Stretchable optoelectronic circuits embedded in a polymer network.
AB  - Stretchable optoelectronic circuits, incorporating chip-level LEDs and
      photodiodes in a silicone membrane, are demonstrated. Due to its highly
      miniaturized design and tissue-like mechanical properties, such an optical
      circuit can be conformally applied to the epidermis and be used for measurement
      of photoplethysmograms. This level of optical functionality in a stretchable
      substrate is potentially of great interest for personal health monitoring. 

PMID- 24282162
TI  - Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type
      2 diabetes mellitus.
AB  - Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a
      higher prevalence of hypogonadism. It still remains unclear the mechanism by
      which there is a relationship between hypogonadism and DM2. The objective was to
      evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal
      patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without
      DM2 (normal glucose tolerance test) as control group (CG) were included. We
      assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii)
      luteinizing hormone (LH) pulsatility through blood collections every 10 min for 4
      h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90
      min after 100 MUg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test:
      basal total testosterone (TT), bioavailable testosterone (BT), free testosterone
      (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin
      (SHBG) and 72 h post 5000 IU of i.m. hCG. There were no differences in age, body
      mass index and waist circumference between groups. Glucose was higher in the DM2
      group vs. CG: 131.1 +/- 25.5 vs. 99.1 +/- 13.6 mg/dL, p = 0.0005. There were no
      difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels
      between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8 +/- 0.8
      vs. 1.5 +/- 0.5 pulses, p = 0.009. Differences in LH pulse amplitude were not
      found. A negative correlation was found between the number of LH pulses and
      glucose, r: -0.39, p = 0.03. There were no differences in the response of LH to
      GnRH between groups nor in the response of sexual steroids and SHBG to hCG.
      Patients with DM2 showed lower hypothalamic pulse frequency without changes in
      the pituitary response to GnRH nor testicular response to hCG. Glucose levels
      negatively correlated with the number of LH pulses which suggests a negative
      effect of hyperglycaemia in the hypothalamic secretion of GnRH. 

PMID- 24282163
TI  - Assessment of fat taste in individuals with and without anorexia nervosa.
AB  - OBJECTIVE: Avoidance of dietary fat is a highly characteristic eating behavior of
      individuals with anorexia nervosa (AN). To date, no study has determined whether
      these individuals are better able to perceive the fat content of foods than
      individuals without AN. The goal of this study was to compare blinded taste
      ratings of fat-free, low fat, and regular cream cheese in patients with AN and in
      normal controls (NC). METHOD: AN (n = 25) and control (NC; n = 25) participants
      were presented with a series of nine cream cheese samples of three differing fat
      contents and asked to taste and rate each sample from very low to very high fat.
      RESULTS: Repeated measures ANOVA found no significant main effect of fat content
      and no interaction between fat content and diagnosis; however, a significant
      three-way interaction between fat content, diagnosis, and trial was observed.
      Post hoc analysis revealed a significant fat content by trial interaction within
      the AN group, suggesting a significant trial effect for the fat-free samples only
      with improving ability to detect fat-free samples over repeated trials.
      DISCUSSION: The current study suggests that individuals with AN do not have a
      markedly greater ability to taste fat than NC, and that; therefore, fat avoidance
      is likely primarily based on cognitive factors.

PMID- 24282164
TI  - Carotenoid metabolism is induced in rice bran during very high temperature
      stress.
AB  - BACKGROUND: Postharvest yellowing (PhY) causes yellowing in rice endosperm during
      conditions of high temperature and moisture. Rice bran was investigated as a
      model tissue for studying PhY and for determining the possibility of carotenoids
      as the source of the yellow color. RESULTS: A survey of different colored rice
      and wild (non-sativa) rice lines resulted in the identification of several purple
      bran lines having very low or no bran carotenoids. Transcription levels of
      phytoene synthase, the first committed step in carotenoid biosynthesis, were
      higher in carotenoid-containing bran, indicating that carotogenesis is an ongoing
      process in mature bran. Bran and endosperm subjected to PhY conditions had a
      similar temperature optimum and color responses, so bran was utilized to
      investigate carotenoid levels and transcription levels of genes for carotogenesis
      during PhY. During PhY, total carotenoid levels in bran increased while levels of
      the predominant xanthophyll carotenoid, lutein, decreased. This difference could
      be explained by carotenoids being metabolized into apocarotenoids, which have
      high antioxidant activities and can be highly colored. This mechanism is further
      supported by the long-term transcription during PhY of CCD1, which encodes an
      enzyme in apocarotenoid production. CONCLUSION: We propose that PhY is an active,
      metabolic response to a very high temperature stress and that the increase in
      total carotenoids in bran during PhY is a result of the production of colored
      apocarotenoids.

PMID- 24282165
TI  - Two-photon laser scanning microscopy as a useful tool for imaging and evaluating
      macrophage-, IL-4 activated macrophage- and osteoclast-based in vitro degradation
      of beta-tricalcium phosphate bone substitute material.
AB  - Two-photon microscopy is an innovative technology that has high potential to
      combine the examination of soft and hard tissues in vitro and in vivo. Calcium
      phosphates are widely used substitutes for bone tissue engineering, since they
      are degradable and consequently replaced by newly formed tissue. It is well known
      that osteoclasts are responsible for the resorption processes during bone
      remodelling. We hypothesize that also macrophages are actively involved in the
      resorption process of calcium phosphate scaffolds and addressed this question in
      in vitro culture systems by two-photon laser scanning microscopy. Beta-tricalcium
      phosphate specimens were incubated with (1) macrophages, (2) interleukin-4
      activated macrophages, and (3) osteoclasts for up to 21 days. Interestingly,
      macrophages degraded beta-tricalcium phosphate specimens in an equivalent fashion
      compared to osteoclasts and significantly more than IL-4 activated macrophages.
      An average of ~32% of the macrophages was partially filled with ceramic material
      while this was 18% for osteoclasts and 9% for IL-4 activated macrophages. For the
      first time by applying two-photon microscopy, our studies show the previously
      unrecognized potential of macrophages to phagocytose ceramic material, which is
      expected to have implication on osteoconductive scaffold design.

PMID- 24282166
TI  - Stabilization of copper catalysts for liquid-phase reactions by atomic layer
      deposition.
AB  - Atomic layer deposition (ALD) of an alumina overcoat can stabilize a base metal
      catalyst (e.g., copper) for liquid-phase catalytic reactions (e.g., hydrogenation
      of biomass-derived furfural in alcoholic solvents or water), thereby eliminating
      the deactivation of conventional catalysts by sintering and leaching. This method
      of catalyst stabilization alleviates the need to employ precious metals (e.g.,
      platinum) in liquid-phase catalytic processing. The alumina overcoat initially
      covers the catalyst surface completely. By using solid state NMR spectroscopy, X
      ray diffraction, and electron microscopy, it was shown that high temperature
      treatment opens porosity in the overcoat by forming crystallites of gamma-Al2 O3
      . Infrared spectroscopic measurements and scanning tunneling microscopy studies
      of trimethylaluminum ALD on copper show that the remarkable stability imparted to
      the nanoparticles arises from selective armoring of under-coordinated copper
      atoms on the nanoparticle surface. 

PMID- 24282167
TI  - Gastric bypass surgery is more efficacious than intensive lifestyle and medical
      treatment for type 2 diabetes remission.

PMID- 24282168
TI  - Stimulant medication for ADHD not associated with subsequent substance use
      disorders.

PMID- 24282169
TI  - Abnormal vaginal bleeding after epidural steroid injection: is there a cause for
      concern?

PMID- 24282170
TI  - Suggestions for improving guideline utility and trustworthiness.

PMID- 24282171
TI  - An interferon-free, all-oral regimen is effective in treatment of genotype 1
      chronic HCV infection.

PMID- 24282172
TI  - Beyond genetics: focusing on maternal environment for congenital heart disease
      prevention.

PMID- 24282173
TI  - Amniotomy has no effect on shortening of spontaneous labour.

PMID- 24282174
TI  - Individual clinical symptoms have limited utility in the diagnosis of obstructive
      sleep apnoea.

PMID- 24282175
TI  - Systematic review suggests TNF-alpha inhibitors may be rational options for
      pregnant patients with inflammatory bowel disease.

PMID- 24282176
TI  - Basic learning concepts in EBM: the bidimentional hierarchy of evidence.

PMID- 24282177
TI  - Peripartum antidepressant use is associated with an increased risk of postpartum
      haemorrhage.

PMID- 24282178
TI  - Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and
      eating disorders: no replication found.
AB  - OBJECTIVE: The female preponderance and onset around puberty in the majority of
      eating disorders (EDs) suggest that sex hormones, like estrogens, may be involved
      in the onset of these disorders. An eight-SNP haplotype at the estrogen receptor
      I (ESR1) gene was found to be associated with anorexia nervosa (AN) (Versini et
      al., Neuropsychopharmacology, 35, 1818-1825, 2010) and three SNPs from this
      haplotype (rs726281, rs2295193, and rs3798577) were associated with AN and/or
      EDs. Our objective was to replicate these findings in an independent cohort of
      520 patients with an eating disorder, of whom 244 had AN (142 restricting type)
      from the GenED study and 2,810 random women from the Netherlands Twin Registry.
      METHOD: The frequencies of the eight-SNP haplotype and three ESR1 SNPs were
      compared between patients with an eating disorder, with AN (restricting type),
      with bulimia nervosa (BN), and the control women. RESULTS: Neither the haplotype
      nor the three ESR1 SNPs were associated with EDs, BN, AN, or restricting type AN.
      DISCUSSION: Despite sufficient statistical power, the associations reported by
      Versini et al. (Neuropsychopharmacology, 35, 1818-1825, 2010) were not
      replicated.

PMID- 24282179
TI  - In children treated for internalising or externalising problems, sudden large
      improvements between sessions is associated with longer term outcomes.

PMID- 24282180
TI  - Review: recommendations for the assessment and management of sleep disorders in
      ADHD.

PMID- 24282181
TI  - Mowat-Wilson syndrome: deafness in the first Egyptian case who was conceived by
      intracytoplasmic sperm injection.
AB  - Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or
      deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome
      is characterized by typical facial features, moderate-to-severe mental
      retardation, epilepsy and variable congenital malformations, including
      Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of
      the corpus callosum, and eye defects. The prevalence of Mowat-Wilson syndrome is
      currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed,
      particularly in patients without Hirschsprung disease. We report here the first
      Egyptian case of Mowat-Wilson syndrome who was conceived by intracytoplasmic
      sperm injection. The patient manifested bilateral sensorineural hearing loss--a
      new feature not previously reported in cases of Mowat-Wilson syndrome. This
      report describes the first Egyptian patient of Mowat-Wilson syndrome who was
      conceived after intracytoplasmic sperm injection, and provides a new evidence for
      the inclusion of deafness among the congenital defects of the syndrome.

PMID- 24282182
TI  - Response to Mtaweh et al.

PMID- 24282183
TI  - Clinical features and molecular characterization of a patient with muscle-eye
      brain disease: a novel mutation in the POMGNT1 gene.
AB  - Muscle-eye-brain disease is a congenital muscular dystrophy characterized by
      structural brain and eye defects. Here, we describe a 12-year-old boy with
      partial agenesis of corpus callosum, ventriculomegaly, flattened brain stem,
      diffuse pachygyria, blindness, profound cognitive deficiencies, and generalized
      muscle weakness, yet without a clear dystrophic pattern on muscle biopsy. There
      was no glycosylation of alpha-dystroglycan and the genetic screening revealed a
      novel truncating mutation, c.1545delC (p.Tyr516Thrfs*21), and a previously
      identified missense mutation, c.1469G>A (p.Cys490Tyr), in the protein O-mannose
      beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene. These findings broaden
      the clinical spectrum of muscle-eye-brain disease to include pronounced hypotonia
      with severe brain and eye malformations, yet with mild histopathologic changes in
      the muscle specimen, despite the absence of glycosylated alpha-dystroglycan. 

PMID- 24282184
TI  - Hidden dense middle cerebral artery sign in a 4-year-old boy with traumatic
      subarachnoid hemorrhage.
AB  - A 4-year-old boy was admitted with acute onset of hemiplegia of the right side
      that was secondary to a traffic accident. Initial computed tomography revealed a
      traumatic subarachnoid hemorrhage, and follow-up computed tomography showed a
      more localized hematoma of the left sylvian cistern. After a few days of
      conservative treatment, magnetic resonance imaging (MRI) revealed a cerebral
      infarction of the left lenticulostriate territory, even though magnetic resonance
      angiography showed preserved middle cerebral artery flow. Thus, we realized that
      the hematoma of the sylvian cistern was the so-called dense middle cerebral
      artery sign. This case of posttraumatic infarction suggested the importance of
      meticulous investigations and clinical correlations of imaging studies in
      pediatric patients with head injuries. 

PMID- 24282185
TI  - Case report: Neuronal migration disorder associated with chromosome 15q13.3
      duplication in a boy with autism and seizures.
AB  - Neuronal migration disorders are a group of disorders that cause structural brain
      abnormalities and varying degrees of neurocognitive impairment, resulting from
      abnormal neuronal migration during brain development. There are several mutations
      that have been associated with these disorders. Here the case of a 4-year-old
      autistic boy is presented, who was found to have evidence of a neuronal migration
      disorder on magnetic resonance imaging (MRI) during a workup for seizures.
      Genetic testing did not reveal any of the gene mutations known to be associated
      with neuronal migration disorders but did reveal a microduplication at chromosome
      15q13.3, a locus that has been previously associated with autism, cognitive
      impairment, and seizures. Although the concurrent presence of the genetic and
      structural abnormalities does not necessarily imply causality, the simultaneous
      independent occurrence of both conditions is certainly unusual. It is possible
      that there may be an association between this duplication syndrome and aberrant
      neuronal migration. 

PMID- 24282186
TI  - Clinical course of atrial fibrillation in older adults: the importance of
      cardiovascular events beyond stroke.
AB  - AIMS: Atrial fibrillation increases the risks of stroke, heart failure, and
      death, and anticoagulation therapy increases the risk of gastrointestinal
      haemorrhage. However, the relative event rates for these outcomes are not well
      described. We sought to define the risks of major clinical events in older adults
      after a new diagnosis of atrial fibrillation. METHODS AND RESULTS: We undertook a
      population-based, retrospective cohort study of a nationally representative
      sample of fee-for-service Medicare beneficiaries 65 years or older with incident
      atrial fibrillation diagnosed between 1999 and 2007. The main outcome measures
      were mortality and hospitalization or emergency department care for heart
      failure, myocardial infarction, stroke, or gastrointestinal haemorrhage. Among
      186 461 patients with atrial fibrillation and no recent hospitalizations for
      heart failure, myocardial infarction, stroke, or gastrointestinal haemorrhage,
      mortality was the most frequent of these major clinical events (19.5% at 1 year;
      48.8% at 5 years). By 5 years, 13.7% of patients were hospitalized for heart
      failure, 7.1% developed new-onset stroke, and 5.7% had gastrointestinal
      haemorrhage. Myocardial infarction was less frequent (3.9% at 5 years). Rates of
      mortality, heart failure, myocardial infarction, stroke, and gastrointestinal
      bleeding increased with older age and higher CHADS2 scores. Among 44 479 patients
      with previous events, the 5-year risk of death was greatest among patients with
      recent bleeding events (70.1%) and stroke (63.7%) and lowest among those with
      recent myocardial infarction (54.9%). CONCLUSION: After the diagnosis of incident
      atrial fibrillation in older adults, mortality was the most frequent major
      outcome during the first 5 years. Among non-fatal cardiovascular events, heart
      failure was the most common event.

PMID- 24282187
TI  - Depression and cardiovascular disease: a clinical review.
AB  - Cardiovascular disease (CVD) and depression are common. Patients with CVD have
      more depression than the general population. Persons with depression are more
      likely to eventually develop CVD and also have a higher mortality rate than the
      general population. Patients with CVD, who are also depressed, have a worse
      outcome than those patients who are not depressed. There is a graded
      relationship: the more severe the depression, the higher the subsequent risk of
      mortality and other cardiovascular events. It is possible that depression is only
      a marker for more severe CVD which so far cannot be detected using our currently
      available investigations. However, given the increased prevalence of depression
      in patients with CVD, a causal relationship with either CVD causing more
      depression or depression causing more CVD and a worse prognosis for CVD is
      probable. There are many possible pathogenetic mechanisms that have been
      described, which are plausible and that might well be important. However, whether
      or not there is a causal relationship, depression is the main driver of quality
      of life and requires prevention, detection, and management in its own right.
      Depression after an acute cardiac event is commonly an adjustment disorder than
      can improve spontaneously with comprehensive cardiac management. Additional
      management strategies for depressed cardiac patients include cardiac
      rehabilitation and exercise programmes, general support, cognitive behavioural
      therapy, antidepressant medication, combined approaches, and probably disease
      management programmes. 

PMID- 24282188
TI  - Atrial fibrillation and prior MI: searching for balance in ischaemic and bleeding
      events in patients treated with factor-specific anticoagulants.

PMID- 24282189
TI  - Developing requirements for a mobile app to support citizens in dealing with
      ticks and tick bites via end-user profiling.
AB  - Tick bites and tick-borne infections are an increasingly large problem. There is
      a wide range of precautions that citizens can take, but compliance is low. Mobile
      technology can offer a solution here, as they allow citizens to access health
      information in context. In this article, we discuss the development of
      requirements for a mobile app to support citizens in dealing with ticks and tick
      bites. First, we identified organizational stakeholders based on relevant
      protocols, and primary end-users via a systematic risk determination procedure.
      Then, we profiled end-users based on 25 in-depth interviews. We consulted
      organizational stakeholders via a focus group. The mobile app should primarily
      motivate citizens to check themselves for tick bites after visiting a risk area.
      The app should also include a tick radar, alerts to remind people to check for
      tick bites, and the possibility to document tick bites. Our experiences underline
      the necessity of thoroughly investigating the designated end-users and their
      context of use in order to tailor preventive health advice, and we demonstrate
      how this can be done. Finally, this case shows the need to create persuasive
      health technology in order to maximize citizen compliance. 

PMID- 24282190
TI  - Fitness for purpose when there are many different purposes: who are electronic
      patient records for?
AB  - Electronic patient record systems serve many purposes for many different kinds of
      users. Four case studies are reported of the use made by health-care staff of
      electronic patient record systems that supported health-care pathways. The
      results demonstrate that the systems fit the purposes of strategic and managerial
      users of the record, but they are problematic as tools for use by the frontline
      staff delivering care. As a result, these staff frequently resort to workarounds
      to accomplish their work goals. An analysis of the design processes that created
      these systems shows that the specification of the systems was based on strategic
      and managerial requirements and there was no formal assessment of the needs of
      frontline users. Efforts to address the needs of frontline staff in the
      provisions of electronic systems were most often made after the main system was
      implemented. 

PMID- 24282191
TI  - Pulmonary malignant peripheral nerve sheath tumour.
AB  - Malignant peripheral nerve sheath tumours (MPNSTs) may occur in any peripheral
      nerve. They are often found in the chest wall and the posterior mediastinum. On
      the other hand, primary pulmonary MPNST is extremely rare, and surgically treated
      cases have been reported. Here, we present 3 cases of primary MPNST originating
      from the pulmonary parenchyma who underwent surgery in our institution. We
      discuss the possible clinical and pathological associations in the view of the
      literature. 

PMID- 24282192
TI  - Hyperthyroidism and psychiatric morbidity: evidence from a Danish nationwide
      register study.
AB  - OBJECTIVE: Thyroid hormones are essential for the normal development of the fetal
      brain, while hyperthyroidism in adults is associated with mood symptoms and
      reduced quality of life. In this study, we aimed to investigate the association
      and temporal relationship between hyperthyroidism and psychiatric morbidity.
      DESIGN: Register-based nationwide cohort study. METHOD: Data on hyperthyroidism
      and psychiatric morbidity were obtained by record linkage of the Danish National
      Patient Registry and the Danish National Prescription Registry. A total of 2631
      hyperthyroid individuals were identified and matched 1:4 with non-hyperthyroid
      controls and followed for a mean duration of 6 years (range 0-13). Logistic and
      Cox regression models were used to assess the risk of psychiatric morbidity
      before and after the diagnosis of hyperthyroidism respectively. RESULTS: BEFORE
      THE DIAGNOSIS OF HYPERTHYROIDISM, SUCH INDIVIDUALS HAD AN INCREASED RISK OF BEING
      HOSPITALIZED WITH PSYCHIATRIC DIAGNOSES (ODDS RATIO (OR): 1.33; 95% CI: 0.98
      1.80) and an increased risk of being treated with antipsychotics (OR: 1.17; 95%
      CI: 1.00-1.38), antidepressants (OR: 1.13; 95% CI: 1.01-1.27), or anxiolytics
      (OR: 1.28; 95% CI: 1.16-1.42). After the diagnosis of hyperthyroidism, there was
      a higher risk of being hospitalized with psychiatric diagnoses (hazard ratio
      (HR): 1.51; 95% CI: 1.11-2.05) and an increased risk of being treated with
      antipsychotics (HR: 1.46; 95% CI: 1.20-1.79), antidepressants (HR: 1.54; 95% CI:
      1.36-1.74), or anxiolytics (HR: 1.47; 95% CI: 1.27-1.69). CONCLUSIONS:
      Hyperthyroid individuals have an increased risk of being hospitalized with
      psychiatric diagnoses and being treated with antipsychotics, antidepressants, and
      anxiolytics, both before and after the diagnosis of hyperthyroidism.

PMID- 24282193
TI  - The association between maternal perception of obstetric and pediatric care
      providers' attitudes and exclusive breastfeeding outcomes.
AB  - BACKGROUND: Exclusive breastfeeding is recommended for 6 months. Successful
      breastfeeding requires support from family members, peers, and health care
      professionals. OBJECTIVE: This study aimed to determine the association between
      maternal perception of the attitudes of obstetric and pediatric care providers
      about infant feeding during the neonatal period and exclusive breastfeeding at 1,
      3, and 6 months. METHODS: The study sample consisted of 1602 women from the
      Infant Feeding Practices Study II (2005-2007), a longitudinal study of women in
      the United States. Analyses included chi-square and Fisher's exact tests and
      logistic regression models. RESULTS: Mothers who perceived that the obstetric
      care provider favored exclusive breastfeeding were significantly more likely to
      exclusively breastfeed their infants at 1 and 3 months (odds ratio [OR] = 1.73,
      95% confidence interval [CI], 1.33-2.24; and OR = 1.41, 95% CI, 1.09-1.80,
      respectively) as compared to mothers who perceived that the obstetric care
      provider was neutral about the type of infant feeding. Similarly, mothers who
      perceived that the pediatric care provider favored exclusive breastfeeding had
      higher odds of exclusively breastfeeding their infants at 1 and 3 months (OR =
      1.53, 95% CI, 1.17-1.99; and OR = 1.51, 95% CI, 1.17-1.95, respectively) as
      compared to mothers who perceived that the pediatric care provider was neutral
      about the type of infant feeding. The association was no longer significant at 6
      months. CONCLUSION: Maternal perception of obstetric and pediatric care
      providers' preference for exclusive breastfeeding during the neonatal period is
      associated with exclusive breastfeeding until 3 months.

PMID- 24282194
TI  - Human milk oligosaccharide composition differs between donor milk and mother's
      own milk in the NICU.
AB  - BACKGROUND: Human milk oligosaccharides (HMO) represent the third most abundant
      component of human breast milk. More than a hundred structurally distinct HMO
      have been identified, and the HMO composition varies between mothers as well as
      over the course of lactation. Some newborn infants receive donor milk (DM) when
      their mother's own milk (MOM) volume is inadequate or unavailable. OBJECTIVE:
      This study aimed to compare HMO content between DM and MOM. METHODS: We used high
      performance liquid chromatography analysis of fluorescently labeled HMO to
      analyze the variation in HMO amount and composition of 31 different batches of DM
      (each pooled from 3 individual donors) provided by the Mothers' Milk Bank in San
      Jose, California, and compared it to 26 different MOM samples donated by mothers
      with infants in our neonatal intensive care unit (NICU). RESULTS: Total HMO
      amount as well as concentrations of lacto-N-tetraose, lacto-N-neotetraose, lacto
      N-fucopentaose 1, and disialyllacto-N-tetraose were significantly lower in DM
      than in MOM, whereas the concentrations of 3'-sialyllactose and 3-fucosyllactose
      were significantly higher in DM. CONCLUSION: Our data show that infants in our
      NICU who receive DM are likely to ingest HMO at different total amounts and
      relative composition from what they would receive with their MOM. Recent in vitro
      and animal studies have started to link individual HMO to infant health and
      disease. Future studies are needed to assess the importance of a mother-infant
      match with regard to HMO composition.

PMID- 24282195
TI  - Wellness, fatigue and physical performance acclimatisation to a 2-week soccer
      camp at 3600 m (ISA3600).
AB  - OBJECTIVES: To examine the time course of wellness, fatigue and performance
      during an altitude training camp (La Paz, 3600 m) in two groups of either sea
      level (Australian) or altitude (Bolivian) native young soccer players. METHODS:
      Wellness and fatigue were assessed using questionnaires and resting heart rate
      (HR) and HR variability. Physical performance was assessed using HR responses to
      a submaximal run, a Yo-Yo Intermittent recovery test level 1 (Yo-YoIR1) and a 20
      m sprint. Most measures were performed daily, with the exception of Yo-YoIR1 and
      20 m sprints, which were performed near sea level and on days 3 and 10 at
      altitude. RESULTS: Compared with near sea level, Australians had moderate-to
      large impairments in wellness and Yo-YoIR1 relative to the Bolivians on arrival
      at altitude. The acclimatisation of most measures to altitude was substantially
      slower in Australians than Bolivians, with only Bolivians reaching near sea-level
      baseline high-intensity running by the end of the camp. Both teams had moderately
      impaired 20 m sprinting at the end of the camp. Exercise HR had large
      associations (r>0.5-0.7) with changes in Yo-YoIR1 in both groups. CONCLUSIONS:
      Despite partial physiological and perceptual acclimatisation, 2 weeks is
      insufficient for restoration of physical performance in young sea-level native
      soccer players. Because of the possible decrement in 20 m sprint time, a greater
      emphasis on speed training may be required during and after altitude training.
      The specific time course of restoration for each variable suggests that they
      measure different aspects of acclimatisation to 3600 m; they should therefore be
      used in combination to assess adaptation to altitude.

PMID- 24282196
TI  - Soccer activity profile of altitude versus sea-level natives during
      acclimatisation to 3600 m (ISA3600).
AB  - OBJECTIVES: We investigated the effect of high altitude on the match activity
      profile of elite youth high altitude and sea level residents. METHODS: Twenty Sea
      Level (Australian) and 19 Altitude-resident (Bolivian) soccer players played five
      games, two near sea level (430 m) and three in La Paz (3600 m). Match activity
      profile was quantified via global positioning system with the peak 5 min period
      for distance ((D5(peak)) and high velocity running (>4.17 m/s, HIVR5(peak)); as
      well as the 5 min period immediately subsequent to the peak for both distance
      (D5(sub)) and high-velocity running (HIVR5(sub)) identified using a rolling 5 min
      epoch. The games at 3600 m were compared with the average of the two near sea
      level games. RESULTS: The total distance per minute was reduced by a small
      magnitude in the first match at altitude in both teams, without any change in low
      velocity running. There were variable changes in HiVR, D5(peak) and HiVR5(peak)
      from match to match for each team. There were within-team reductions in D5(peak)
      in each game at altitude compared with those at near sea level, and this
      reduction was greater by a small magnitude in Australians than Bolivians in game
      4. The effect of altitude on HiVR5(peak) was moderately lower in Australians
      compared with Bolivians in game 3. There was no clear difference in the effect of
      altitude on maximal accelerations between teams. CONCLUSIONS: High altitude
      reduces the distance covered by elite youth soccer players during matches.
      Neither 13 days of acclimatisation nor lifelong residence at high altitude
      protects against detrimental effects of altitude on match activity profile.

PMID- 24282197
TI  - The sleep of elite athletes at sea level and high altitude: a comparison of sea
      level natives and high-altitude natives (ISA3600).
AB  - BACKGROUND: Altitude exposure causes acute sleep disruption in non-athletes, but
      little is known about its effects in elite athletes. The aim of this study was to
      examine the effects of altitude on two groups of elite athletes, that is, sea
      level natives and high-altitude natives. METHODS: Sea-level natives were members
      of the Australian under-17 soccer team (n=14). High-altitude natives were members
      of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19
      nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz
      (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on
      every day/night using activity monitors. RESULTS: The Australians' sleep was
      shorter, and of poorer quality, on the first night at altitude compared with sea
      level. Sleep quality returned to normal by the end of the first week at altitude,
      but sleep quantity had still not stabilised at its normal level after 2 weeks.
      The quantity and quality of sleep obtained by the Bolivians was similar, or
      greater, on all nights at altitude compared with sea level. The Australians
      tended to obtain more sleep than the Bolivians at sea level and altitude, but the
      quality of the Bolivians' sleep tended to be better than that of the Australians
      at altitude. CONCLUSIONS: Exposure to high altitude causes acute and chronic
      disruption to the sleep of elite athletes who are sea-level natives, but it does
      not affect the sleep of elite athletes who are high-altitude natives.

PMID- 24282198
TI  - On the use of mobile inflatable hypoxic marquees for sport-specific altitude
      training in team sports.
AB  - BACKGROUND/AIM: With the evolving boundaries of sports science and greater
      understanding of the driving factors in the human performance physiology, one of
      the limiting factors has now become the technology. The growing scientific
      interest on the practical application of hypoxic training for intermittent
      activities such as team and racket sports legitimises the development of
      innovative technologies serving athletes in a sport-specific setting. METHODS:
      Description of a new mobile inflatable simulated hypoxic equipment. RESULTS: The
      system comprises two inflatable units-that is, a tunnel and a rectangular design,
      each with a 215 m(3) volume and a hypoxic trailer generating over 3000 Lpm of
      hypoxic air with FiO2 between 0.21 and 0.10 (a simulated altitude up to 5100 m).
      The inflatable units offer a 45 m running lane (width=1.8 m and height=2.5 m) as
      well as a 8 m * 10 m dome tent. FiO2 is stable within a range of 0.1% in normal
      conditions inside the tunnel. The air supplied is very dry-typically 10-15%
      relative humidity. CONCLUSIONS: This mobile inflatable simulated hypoxic
      equipment is a promising technological advance within sport sciences. It offers
      an opportunity for team-sport players to train under hypoxic conditions, both for
      repeating sprints (tunnel configuration) or small-side games (rectangular
      configuration).

PMID- 24282199
TI  - Predicting sickness during a 2-week soccer camp at 3600 m (ISA3600).
AB  - OBJECTIVES: To examine the time course of changes in wellness and health status
      markers before and after episodes of sickness in young soccer players during a
      high-altitude training camp (La Paz, 3600 m). METHODS: Wellness and fatigue were
      assessed daily on awakening using specifically-designed questionnaires and
      resting measures of heart rate and heart rate variability. The rating of
      perceived exertion and heart rate responses to a submaximal run (9 km/h) were
      also collected during each training session. Players who missed the morning
      screening for at least two consecutive days were considered as sick. RESULTS:
      Four players met the inclusion criteria. With the exception of submaximal
      exercise heart rate, which showed an almost certain and large increase before the
      day of sickness (4%; 90% confidence interval 3 to 6), there was no clear change
      in any of the other psychometric or physiological variables. There was a very
      likely moderate increase (79%, 22 to 64) in self-reported training load the day
      before the heart rate increase in sick players (4 of the 4 players, 100%). In
      contrast, training load was likely and slightly decreased (-24%, -78 to -11) in
      players who also showed an increased heart rate but remained healthy.
      CONCLUSIONS: A >4% increased heart rate during submaximal exercise in response to
      a moderate increase in perceived training load the previous day may be an
      indicator of sickness the next day. All other variables, that is, resting heart
      rate, heart rate variability and psychometric questionnaires may be less powerful
      at predicting sickness.

PMID- 24282201
TI  - Improving team-sport player's physical performance with altitude training: from
      beliefs to scientific evidence.

PMID- 24282200
TI  - Determinants of team-sport performance: implications for altitude training by
      team-sport athletes.
AB  - Team sports are increasingly popular, with millions of participants worldwide.
      Athletes engaged in these sports are required to repeatedly produce skilful
      actions and maximal or near-maximal efforts (eg, accelerations, changes in pace
      and direction, sprints, jumps and kicks), interspersed with brief recovery
      intervals (consisting of rest or low-intensity to moderate-intensity activity),
      over an extended period of time (1-2 h). While performance in most team sports is
      dominated by technical and tactical proficiencies, successful team-sport athletes
      must also have highly-developed, specific, physical capacities. Much effort goes
      into designing training programmes to improve these physical capacities, with
      expected benefits for team-sport performance. Recently, some team sports have
      introduced altitude training in the belief that it can further enhance team-sport
      physical performance. Until now, however, there is little published evidence
      showing improved team-sport performance following altitude training, despite the
      often considerable expense involved. In the absence of such studies, this review
      will identify important determinants of team-sport physical performance that may
      be improved by altitude training, with potential benefits for team-sport
      performance. These determinants can be broadly described as factors that enhance
      either sprint performance or the ability to recover from maximal or near-maximal
      efforts. There is some evidence that some of these physical capacities may be
      enhanced by altitude training, but further research is required to verify that
      these adaptations occur, that they are greater than what could be achieved by
      appropriate sea-level training and that they translate to improved team-sport
      performance. 

PMID- 24282202
TI  - Update in the understanding of altitude-induced limitations to performance in
      team-sport athletes.
AB  - The internationalism of field-based team sports (TS) such as football and rugby
      requires teams to compete in tournaments held at low to moderate altitude (~1200
      2500 m). In TS, acceleration, speed and aerobic endurance are physical
      characteristics associated with ball possession and, ultimately, scoring. While
      these qualities are affected by the development of neuromuscular fatigue at sea
      level, arterial hypoxaemia induced by exposure to altitude may further hinder the
      capacity to perform consecutive accelerations (CAC) or sprint endurance and
      thereby change the outcome of a match. The higher the altitude, the more severe
      the hypoxaemia, and thus, the larger the expected decline in aerobic endurance,
      CAC and match running performance. Therefore, it is critical for athletes and
      coaches to understand how arterial hypoxaemia affects aerobic endurance and CAC
      and the magnitude of decline they may face at altitude for optimal preparation
      and increased chances of success. This mini review summarises the effects of
      acute altitude/hypoxia exposure on aerobic endurance, CAC and activity profiles
      of TS athletes performing in the laboratory and during matches at natural
      altitude, and analyses the latest findings about the consequences of arterial
      hypoxaemia on the relationship between peripheral perturbations, neural
      adjustments and performance during repeated sprints or CAC. Finally, we briefly
      discuss how altitude training can potentially help athletes prepare for
      competition at altitude. 

PMID- 24282203
TI  - Relationship between changes in haemoglobin mass and maximal oxygen uptake after
      hypoxic exposure.
AB  - BACKGROUND: Endurance athletes have been using altitude training for decades to
      improve near sea-level performance. The predominant mechanism is thought to be
      accelerated erythropoiesis increasing haemoglobin mass (Hb(mass)) resulting in a
      greater maximal oxygen uptake (VO2(max)). Not all studies have shown a
      proportionate increase in VO2(max) as a result of increased Hb(mass). The aim of
      this study was to determine the relationship between the two parameters in a
      large group of endurance athletes after altitude training. METHODS: 145 elite
      endurance athletes (94 male and 51 female) who participated in various altitude
      studies as altitude or control participants were used for the analysis.
      Participants performed Hb(mass) and VO2(max) testing before and after
      intervention. RESULTS: For the pooled data, the correlation between per cent
      change in Hb(mass) and per cent change in VO2(max) was significant (p<0.0001,
      r(2)=0.15), with a slope (95% CI) of 0.48 (0.30 to 0.67) intercept free to vary
      and 0.62 (0.46 to 0.77) when constrained through the origin. When separated, the
      correlations were significant for the altitude and control groups, with the
      correlation being stronger for the altitude group (slope of 0.57 to 0.72).
      CONCLUSIONS: With high statistical power, we conclude that altitude training of
      endurance athletes will result in an increase in VO2(max) of more than half the
      magnitude of the increase in Hb(mass), which supports the use of altitude
      training by athletes. But race performance is not perfectly related to relative
      VO2(max), and other non-haematological factors altered from altitude training,
      such as running economy and lactate threshold, may also be beneficial to
      performance.

PMID- 24282205
TI  - Could altitude training benefit team-sport athletes?

PMID- 24282204
TI  - Altitude training and haemoglobin mass from the optimised carbon monoxide
      rebreathing method determined by a meta-analysis.
AB  - OBJECTIVE: To characterise the time course of changes in haemoglobin mass
      (Hbmass) in response to altitude exposure. METHODS: This meta-analysis uses raw
      data from 17 studies that used carbon monoxide rebreathing to determine Hbmass
      prealtitude, during altitude and postaltitude. Seven studies were classic
      altitude training, eight were live high train low (LHTL) and two mixed classic
      and LHTL. Separate linear-mixed models were fitted to the data from the 17
      studies and the resultant estimates of the effects of altitude used in a random
      effects meta-analysis to obtain an overall estimate of the effect of altitude,
      with separate analyses during altitude and postaltitude. In addition, within
      subject differences from the prealtitude phase for altitude participant and all
      the data on control participants were used to estimate the analytical SD. The
      'true' between-subject response to altitude was estimated from the within-subject
      differences on altitude participants, between the prealtitude and during-altitude
      phases, together with the estimated analytical SD. RESULTS: During-altitude
      Hbmass was estimated to increase by ~1.1%/100 h for LHTL and classic altitude.
      Postaltitude Hbmass was estimated to be 3.3% higher than prealtitude values for
      up to 20 days. The within-subject SD was constant at ~2% for up to 7 days between
      observations, indicative of analytical error. A 95% prediction interval for the
      'true' response of an athlete exposed to 300 h of altitude was estimated to be
      1.1-6%. CONCLUSIONS: Camps as short as 2 weeks of classic and LHTL altitude will
      quite likely increase Hbmass and most athletes can expect benefit.

PMID- 24282206
TI  - The individual response to training and competition at altitude.
AB  - Performance in athletic activities that include a significant aerobic component
      at mild or moderate altitudes shows a large individual variation.
      Physiologically, a large portion of the negative effect of altitude on exercise
      performance can be traced to limitations of oxygen diffusion, either at the level
      of the alveoli or the muscle microvasculature. In the lung, the ability to
      maintain arterial oxyhaemoglobin saturation (SaO2) appears to be a primary
      factor, ultimately influencing oxygen delivery to the periphery. SaO2 in hypoxia
      can be defended by increasing ventilatory drive; however, during heavy exercise,
      many athletes demonstrate limitations to expiratory flow and are unable to
      increase ventilation in hypoxia. Additionally, increasing ventilatory work in
      hypoxia may actually be negative for performance, if dyspnoea increases or muscle
      blood flow is reduced secondary to an increased sympathetic outflow (eg, the
      muscle metaboreflex response). Taken together, some athletes are clearly more
      negatively affected during exercise in hypoxia than other athletes. With careful
      screening, it may be possible to develop a protocol for determining which
      athletes may be the most negatively affected during competition and/or training
      at altitude.

PMID- 24282207
TI  - Advancing hypoxic training in team sports: from intermittent hypoxic training to
      repeated sprint training in hypoxia.
AB  - Over the past two decades, intermittent hypoxic training (IHT), that is, a method
      where athletes live at or near sea level but train under hypoxic conditions, has
      gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic'
      or 'anaerobic' interval training, it is believed that IHT would potentiate
      greater performance improvements compared to similar training at sea level. A
      thorough analysis of studies including IHT, however, leads to strikingly poor
      benefits for sea-level performance improvement, compared to the same training
      method performed in normoxia. Despite the positive molecular adaptations observed
      after various IHT modalities, the characteristics of optimal training stimulus in
      hypoxia are still unclear and their functional translation in terms of whole-body
      performance enhancement is minimal. To overcome some of the inherent limitations
      of IHT (lower training stimulus due to hypoxia), recent studies have successfully
      investigated a new training method based on the repetition of short (<30 s) 'all
      out' sprints with incomplete recoveries in hypoxia, the so-called repeated sprint
      training in hypoxia (RSH). The aims of the present review are therefore
      threefold: first, to summarise the main mechanisms for interval training and
      repeated sprint training in normoxia. Second, to critically analyse the results
      of the studies involving high-intensity exercises performed in hypoxia for sea
      level performance enhancement by differentiating IHT and RSH. Third, to discuss
      the potential mechanisms underpinning the effectiveness of those methods, and
      their inherent limitations, along with the new research avenues surrounding this
      topic. 

PMID- 24282208
TI  - Year-to-year variability in haemoglobin mass response to two altitude training
      camps.
AB  - AIM: To quantify the year-to-year variability of altitude-induced changes in
      haemoglobin mass (Hb(mass)) in elite team-sport athletes. METHODS: 12 Australian
      Footballers completed a 19-day (ALT1) and 18-day (ALT2) moderate altitude (~2100
      m), training camp separated by 12 months. An additional 20 participants completed
      only one of the two training camps (ALT1 additional n=9, ALT2 additional n=11).
      Total Hb(mass) was assessed using carbon monoxide rebreathing before (PRE), after
      (POST1) and 4 weeks after each camp. The typical error of Hb(mass) for the pooled
      data of all 32 participants was 2.6%. A contemporary statistics analysis was used
      with the smallest worthwhile change set to 2% for Hb(mass). RESULTS: POST1
      Hb(mass) was very likely increased in ALT1 (3.6 +/- 1.6%, n=19; mean +/- ~90 CL)
      as well as ALT2 (4.4 +/- 1.3%, n=23) with an individual responsiveness of 1.3%
      and 2.2%, respectively. There was a small correlation between ALT1 and ALT2
      (R=0.21, p=0.59) for a change in Hb(mass), but a moderately inverse relationship
      between the change in Hb(mass) and initial relative Hb(mass) (g/kg (R=-0.51,
      p=0.04)). CONCLUSIONS: Two preseason moderate altitude camps 1 year apart yielded
      a similar (4%) mean increase in Hb(mass) of elite footballers, with an individual
      responsiveness of approximately half the group mean effect, indicating that most
      players gained benefit. Nevertheless, the same individuals generally did not
      change their Hb(mass) consistently from year to year. Thus, a 'responder' or 'non
      responder' to altitude for Hb(mass) does not appear to be a fixed trait.

PMID- 24282209
TI  - Adding heat to the live-high train-low altitude model: a practical insight from
      professional football.
AB  - OBJECTIVES: To examine with a parallel group study design the performance and
      physiological responses to a 14-day off-season 'live high-train low in the heat'
      training camp in elite football players. METHODS: Seventeen professional
      Australian Rules Football players participated in outdoor football-specific
      skills (32 +/- 1 degrees C, 11.5 h) and indoor strength (23 +/- 1 degrees C, 9.3
      h) sessions and slept (12 nights) and cycled indoors (4.3 h) in either normal air
      (NORM, n=8) or normobaric hypoxia (14 +/- 1 h/day, FiO2 15.2-14.3%, corresponding
      to a simulated altitude of 2500-3000 m, hypoxic (HYP), n=9). They completed the
      Yo-Yo Intermittent Recovery level 2 (Yo-YoIR2) in temperate conditions (23 +/- 1
      degrees C, normal air) precamp (Pre) and postcamp (Post). Plasma volume (PV) and
      haemoglobin mass (Hb(mass)) were measured at similar times and 4 weeks postcamp
      (4WPost). Sweat sodium concentration ((Na(+))(sweat)) was measured Pre and Post
      during a heat-response test (44 degrees C). RESULTS: Both groups showed very
      large improvements in Yo-YoIR2 at Post (+44%; 90% CL 38, 50), with no between
      group differences in the changes (-1%; -9, 9). Postcamp, large changes in PV
      (+5.6%; -1.8, 5.6) and (Na(+))sweat (-29%; -37, -19) were observed in both
      groups, while Hb(mass) only moderately increased in HYP (+2.6%; 0.5, 4.5). At
      4WPost, there was a likely slightly greater increase in Hb(mass) (+4.6%; 0.0,
      9.3) and PV (+6%; -5, 18, unclear) in HYP than in NORM. CONCLUSIONS: The
      combination of heat and hypoxic exposure during sleep/training might offer a
      promising 'conditioning cocktail' in team sports.

PMID- 24282210
TI  - Hypoxic training and team sports: a challenge to traditional methods?

PMID- 24282211
TI  - Ten days of simulated live high:train low altitude training increases Hbmass in
      elite water polo players.
AB  - OBJECTIVES: Water polo requires high aerobic power to meet the demands of match
      play. Live high:train low (LHTL) may enhance aerobic capacity at sea level.
      Before the Olympics, the Australian women's water polo team utilised LHTL in an
      attempt to enhance aerobic fitness. METHODS: Over 6 months, 11 players completed
      three normobaric LHTL exposures (block 1:11 days at 3000 m; block 2+3:9 days at
      2500 m, 11 days normoxia, 10 days at 2800 m). Haemoglobin mass (Hbmass) was
      measured through carbon monoxide-rebreathing. Before each block, the relationship
      between Hbmass and water polo-specific aerobic fitness was investigated using the
      Multistage Shuttle Swim Test (MSST). Effect size statistics were adopted with
      likely, highly likely and almost certainly results being >75%, >95%, >99%,
      respectively. A Pearson product moment correlation was used to characterise the
      association between pooled data of Hbmass and MSST. RESULTS: Hbmass (mean +/- SD,
      pre 721 +/- 66 g) likely increased after block 1 and almost certainly after block
      2+3 (% change; 90% confidence limits: block 1: 3.7%; 1.3-6.2%, block 2+3: 4.5%;
      3.8-5.1%) and the net effect was almost certainly higher after block 2+3 than
      before block 1 (pre) by 8.5%; 7.3-9.7%. There was a very large correlation
      between Hbmass (g/kg) and MSST score (r=0.73). CONCLUSIONS: LHTL exposures of <2
      weeks induced approximately 4% increase in Hbmass of water polo players. Extra
      Hbmass may increase aerobic power, but since match performance is nuanced by many
      factors it is impossible to ascertain whether the increased Hbmass contributed to
      Australia's Bronze medal.

PMID- 24282212
TI  - Repeated sprint training in normobaric hypoxia.
AB  - Repeated sprint ability (RSA) is a critical success factor for intermittent sport
      performance. Repeated sprint training has been shown to improve RSA, we
      hypothesised that hypoxia would augment these training adaptations. Thirty male
      well-trained academy rugby union and rugby league players (18.4 +/- 1.5 years,
      1.83 +/- 0.07 m, 88.1 +/- 8.9 kg) participated in this single-blind repeated
      sprint training study. Participants completed 12 sessions of repeated sprint
      training (10 * 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO2) or
      normoxia (21% FiO2). Pretraining and post-training, participants completed sports
      specific endurance and sprint field tests and a 10 * 6 s RSA test on a non
      motorised treadmill while measuring speed, heart rate, capillary blood lactate,
      muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent
      Recovery Level 1 test performance improved after RS training in both groups, but
      gains were significantly greater in the hypoxic (33 +/- 12%) than the normoxic
      group (14 +/- 10%, p<0.05). During the 10 * 6 s RS test there was a tendency for
      greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9 +/- 9%,
      normoxic (-0.3 +/- 8.8%, p=0.06) and reductions in cerebral deoxygenation (%
      changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS
      training sessions in hypoxia resulted in twofold greater improvements in capacity
      to perform repeated aerobic high intensity workout than an equivalent normoxic
      training. Performance gains are evident in the short term (4 weeks), a period
      similar to a preseason training block.

PMID- 24282214
TI  - Methods of the international study on soccer at altitude 3600 m (ISA3600).
AB  - BACKGROUND: We describe here the 3-year process underpinning a multinational
      collaboration to investigate soccer played at high altitude--La Paz, Bolivia
      (3600 m). There were two main aims: first, to quantify the extent to which
      running performance would be altered at 3600 m compared with near sea level; and
      second, to characterise the time course of acclimatisation of running performance
      and underlying physiology to training and playing at 3600 m. In addition, this
      project was able to measure the physiological changes and the effect on running
      performance of altitude-adapted soccer players from 3600 m playing at low
      altitude. METHODS: A U20 Bolivian team ('The Strongest' from La Paz, n=19) played
      a series of five games against a U17 team from sea level in Australia (The Joeys,
      n=20). 2 games were played near sea level (Santa Cruz 430 m) over 5 days and then
      three games were played in La Paz over the next 12 days. Measures were (1) game
      and training running performance--including global positioning system (GPS) data
      on distance travelled and velocity of movement; (2) blood--including haemoglobin
      mass, blood volume, blood gases and acid-base status; (3) acclimatisation-
      including resting heart rate variability, perceived altitude sickness, as well as
      heart rate and perceived exertion responses to a submaximal running test; and (4)
      sleep patterns. CONCLUSIONS: Pivotal to the success of the project were the
      strong professional networks of the collaborators, with most exceeding 10 years,
      the links of several of the researchers to soccer federations, as well as the
      interest and support of the two head coaches.

PMID- 24282213
TI  - Position statement--altitude training for improving team-sport players'
      performance: current knowledge and unresolved issues.
AB  - Despite the limited research on the effects of altitude (or hypoxic) training
      interventions on team-sport performance, players from all around the world
      engaged in these sports are now using altitude training more than ever before. In
      March 2013, an Altitude Training and Team Sports conference was held in Doha,
      Qatar, to establish a forum of research and practical insights into this rapidly
      growing field. A round-table meeting in which the panellists engaged in focused
      discussions concluded this conference. This has resulted in the present position
      statement, designed to highlight some key issues raised during the debates and to
      integrate the ideas into a shared conceptual framework. The present signposting
      document has been developed for use by support teams (coaches, performance
      scientists, physicians, strength and conditioning staff) and other professionals
      who have an interest in the practical application of altitude training for team
      sports. After more than four decades of research, there is still no consensus on
      the optimal strategies to elicit the best results from altitude training in a
      team-sport population. However, there are some recommended strategies discussed
      in this position statement to adopt for improving the acclimatisation process
      when training/competing at altitude and for potentially enhancing sea-level
      performance. It is our hope that this information will be intriguing, balanced
      and, more importantly, stimulating to the point that it promotes constructive
      discussion and serves as a guide for future research aimed at advancing the
      bourgeoning body of knowledge in the area of altitude training for team sports. 

PMID- 24282215
TI  - The impact of altitude on the sleep of young elite soccer players (ISA3600).
AB  - BACKGROUND: Altitude training is used by elite athletes to improve sports
      performance, but it may also disrupt sleep. The aim of this study was to examine
      the effects of 2 weeks at high altitude on the sleep of young elite athletes.
      METHODS: Participants (n=10) were members of the Australian under-17 soccer team
      on an 18-day (19-night) training camp in Bolivia, with six nights at near sea
      level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m).
      Sleep was monitored using polysomnography during a baseline night at 430 m and
      three nights at 3600 m (immediately after ascent, 1 week after ascent and 2 weeks
      after ascent). Data were analysed using effect size statistics. RESULTS: All
      results are reported as comparisons with baseline. Rapid eye movement (REM) sleep
      was likely lower immediately upon ascent to altitude, possibly lower after 1 week
      and similar after 2 weeks. On all three nights at altitude, hypopneas and
      desaturations were almost certainly higher; oxygen saturation was almost
      certainly lower; and central apnoeas, respiratory arousals and periodic breathing
      were very likely higher. The effects on REM sleep were common to all but one
      participant, but the effects on breathing were specific to only half the
      participants. CONCLUSIONS: The immediate effects of terrestrial altitude of 3600
      m are to reduce the amount of REM sleep obtained by young elite athletes, and to
      cause 50% of them to have impaired breathing during sleep. REM sleep returns to
      normal after 2 weeks at altitude, but impaired breathing does not improve.

PMID- 24282216
TI  - Changes in blood gas transport of altitude native soccer players near sea-level
      and sea-level native soccer players at altitude (ISA3600).
AB  - OBJECTIVES: The optimal strategy for soccer teams playing at altitude is not
      known, that is, 'fly-in, fly-out' versus short-term acclimatisation. Here, we
      document changes in blood gas and vascular volumes of sea-level (Australian,
      n=20) and altitude (Bolivian, n=19) native soccer players at 3600 m. METHODS:
      Haemoglobin-oxygen saturation (Hb-sO2), arterial oxygen content (CaO2),
      haemoglobin mass (Hbmass), blood volume (BV) and blood gas concentrations were
      measured before descent (Bolivians only), together with aerobic fitness (via Yo
      YoIR1), near sea-level, after ascent and during 13 days at 3600 m. RESULTS: At
      baseline, haemoglobin concentration [Hb] and Hbmass were higher in Bolivians
      (mean +/- SD; 18.2 +/- 1.0 g/dL, 12.8 +/- 0.8 g/kg) than Australians (15.0 +/-
      0.9 g/dL, 11.6 +/- 0.7 g/kg; both p <= 0.001). Near sea-level, [Hb] of Bolivians
      decreased to 16.6 +/- 0.9 g/dL, but normalised upon return to 3600 m; Hbmass was
      constant regardless of altitude. In Australians, [Hb] increased after 12 days at
      3600 m to 17.3 +/- 1.0 g/dL; Hbmass increased by 3.0 +/- 2.7% (p <= 0.01). BV
      decreased in both teams at altitude by ~400 mL. Arterial partial pressure for
      oxygen (PaO2), Hb-sO2 and CaO2 of both teams decreased within 2 h of arrival at
      3600 m (p <= 0.001) but increased over the following days, with CaO2
      overcompensated in Australians (+1.7 +/- 1.2 mL/100 mL; p <= 0.001). Yo-YoIR1 was
      lower on the 3rd versus 10th day at altitude and was significantly related to
      CaO2. CONCLUSIONS: The marked drop in PaO2 and CaO2 observed after ascent does
      not support the 'fly-in, fly-out' approach for soccer teams to play immediately
      after arrival at altitude. Although short-term acclimatisation was sufficient for
      Australians to stabilise their CaO2 (mostly due to loss of plasma volume), 12
      days appears insufficient to reach chronic levels of adaption.

PMID- 24282217
TI  - Primary testicular lymphoma.
AB  - Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of
      extranodal lymphoma. The vast majority of cases are histologically diffuse large
      B-cell lymphoma, but rarer subtypes are clinically important and must be
      recognized. In this review, we discuss the incidence, clinical presentation, and
      prognostic factors of PTL and present a summary of the recent advances in our
      understanding of its pathophysiology, which may account for the characteristic
      clinical features. Although outcomes for patients with PTL have historically been
      poor, significant gains have been made with the successive addition of
      radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and
      central nervous system-directed prophylaxis. We describe the larger retrospective
      series and prospective clinical trials and critically examine the role of RT.
      Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisone given every 21 days with intrathecal methotrexate and locoregional RT
      is the current international standard of care, a substantial minority of patients
      progress, representing an unmet medical need. Finally, we discuss new treatment
      approaches and recent discoveries that may translate into improved outcomes for
      patients with PTL. 

PMID- 24282219
TI  - The decline of our physical examination skills: is echocardiography to blame?

PMID- 24282218
TI  - MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia
      cells.
AB  - Blasts from approximately one-third of patients with acute myeloid leukemia (AML)
      harbor activating mutations in the FMS-like tyrosine kinase 3 (FLT3) receptor
      tyrosine kinase that confer a poor prognosis. The Mucin 1-C-terminal subunit
      (MUC1-C) oncoprotein is aberrantly expressed in AML blasts and stem cells;
      however, there is no known interaction between MUC1-C and FLT3. The present
      studies demonstrate that MUC1-C associates with wild-type and mutant FLT3 in AML
      cells. Targeting MUC1-C with the cell-penetrating peptide inhibitor GO-203
      disrupts MUC1-C/FLT3 complexes and downregulates FLT3 activation. GO-203
      treatment of AML cells was also associated with inhibition of the FLT3 downstream
      effectors AKT, extracellular signal-regulated kinase, and STAT5. The results
      further show that AML cells with FLT3-activating mutations and resistant to the
      FLT3 inhibitor midostaurin/PKC412 are sensitive to GO-203-induced growth arrest
      and death. Moreover, GO-203 increases sensitivity of mutant FLT3 AML cells to
      FLT3 inhibitor treatment. These results indicate that MUC1-C contributes to FLT3
      activation in AML cells and that targeting MUC1-C inhibits the FLT3 signaling
      pathway. Our findings support the development of MUC1-C inhibitors alone and in
      combination with agents that target FLT3 for the treatment of wild-type and
      mutant FLT3 AML. 

PMID- 24282220
TI  - Optimization and comparison of myocardial T1 techniques at 3T in patients with
      aortic stenosis.
AB  - AIMS: To determine the optimal T1 mapping approach to assess myocardial fibrosis
      at 3T. METHODS AND RESULTS: T1 mapping was performed at 3T using the modified
      look-locker-inversion sequence in 20 healthy volunteers and 20 patients with
      aortic stenosis (AS). Pre- and post-contrast myocardial T1, the partition
      coefficient (lambda; DeltaRmyocardium/DeltaRblood, where DeltaR = 1/post-contrast
      T1 - 1/pre-contrast T1), and extracellular volume fraction [ECV; lambda (1 -
      haematocrit)] were assessed. After establishing the optimal time point and
      myocardial region for analysis, we compared the reproducibility of these T1
      measures and their ability to differentiate asymptomatic patients with AS from
      healthy volunteers. There was no segmental variation across the ventricle in any
      of the T1 measures evaluated. lambda and ECV did not vary with time, while post
      contrast T1 was relatively constant between 15 and 30 min. Thus, mid-cavity
      myocardium at 20 min was used for subsequent analyses. ECV displayed excellent
      intra-, inter-observer, and scan-rescan reproducibility [intra-class correlation
      coefficients (ICC) 1.00, 0.97, and 0.96, respectively], as did lambda (ICC 0.99,
      0.94, 0.93, respectively). Moreover, ECV and lambda were both higher in patients
      with AS compared with controls (ECV 28.3 +/- 1.7 vs. 26.0 +/- 1.6%, P < 0.001;
      lambda 0.46 +/- 0.03 vs. 0.44 +/- 0.03, P = 0.02), with the former offering
      improved differentiation. In comparison, scan-rescan reproducibilities for pre-
      and post-contrast myocardial T1 were only modest (ICC 0.72 and 0.56) with no
      differences in values observed between cases and controls (both P> 0.05).
      CONCLUSIONS: ECV appears to be the most promising measure of diffuse myocardial
      fibrosis at 3T based upon its superior reproducibility and ability to
      differentiate disease from health.

PMID- 24282222
TI  - Motion perception and driving: predicting performance through testing and
      shortening braking reaction times through training.
AB  - PURPOSE: A driving simulator was used to examine the relationship between motion
      perception and driving performance. Although motion perception test scores have
      been shown to be related to driving safety, it is not clear which combination of
      tests are the best predictors and whether motion perception training can improve
      driving performance. METHODS: In experiment 1, 60 younger drivers (22.4 +/- 2.5
      years) completed three motion perception tests (2-dimensional [2D] motion-defined
      letter [MDL] identification, 3D motion in depth sensitivity [MID], and dynamic
      visual acuity [DVA]) followed by two driving tests (emergency braking [EB] and
      hazard perception [HP]). In experiment 2, 20 drivers (21.6 +/- 2.1 years)
      completed 6 weeks of motion perception training (using the MDL, MID, and DVA
      tests), while 20 control drivers (22.0 +/- 2.7 years) completed an online driving
      safety course. The EB performance was measured before and after training.
      RESULTS: In experiment 1, MDL (r = 0.34) and MID (r = 0.46) significantly
      correlated with EB score. The change in DVA score as a function of target speed
      (i.e., "velocity susceptibility") was correlated most strongly with HP score (r =
      -0.61). In experiment 2, the motion perception training group had a significant
      decrease in brake reaction time on the EB test from pre- to posttreatment, while
      there was no significant change for the control group: t(38) = 2.24, P = 0.03.
      CONCLUSIONS: Tests of 3D motion perception are the best predictor of EB, while
      DVA velocity susceptibility is the best predictor of hazard perception. Motion
      perception training appears to result in faster braking responses.

PMID- 24282221
TI  - Estimation of retinal ganglion cell loss in glaucomatous eyes with a relative
      afferent pupillary defect.
AB  - PURPOSE: To estimate retinal ganglion cell (RGC) losses associated with a
      relative afferent pupillary defect (RAPD) in glaucoma. METHODS: A cross-sectional
      study was conducted including both eyes of 103 participants from the Diagnostic
      Innovations in Glaucoma Study. A total of 77 subjects had glaucoma in at least
      one eye and 26 were healthy. Pupil responses were assessed using an automated
      pupillometer that records the magnitude of RAPD as an "RAPD score." Standard
      automated perimetry (SAP) and optical coherence tomography (OCT) also were
      performed. Retinal ganglion cell counts were estimated using empirical formulas
      that combine estimates from SAP and OCT. The estimated percentage RGC loss was
      calculated using the combined structure function index (CSFI). RESULTS: There was
      good correlation between RAPD magnitude and intereye differences in estimated
      RGCs (R(2) = 0.492, P < 0.001), mean deviation (R(2) = 0.546, P < 0.001), retinal
      nerve fiber layer thickness (R(2) = 0.362, P < 0.001), and CSFI (R(2) = 0.484, P
      < 0.001). Therefore, a high RAPD score is likely to indicate large asymmetric RGC
      losses. The relationship between intereye difference in RGC counts and RAPD score
      was described best by the formula; RGC difference = 21,896 + 353,272 * RAPD
      score. No healthy subjects had an absolute RAPD score > 0.3, which was associated
      with asymmetry of 105,982 cells (or 12%). CONCLUSIONS: Good correlation between
      the magnitude of RAPD and intereye differences in mean deviation and estimated
      RGC counts suggests pupillometry may be useful for quantifying asymmetric damage
      in glaucoma. (ClinicalTrials.gov number, NCT00221897.).

PMID- 24282223
TI  - Eye movement alterations during reading in patients with early Alzheimer disease.
AB  - PURPOSE: Eye movements follow a reproducible pattern during normal reading. Each
      eye movement ends up in a fixation point, which allows the brain to process the
      incoming information and to program the following saccade. Alzheimer disease (AD)
      produces eye movement abnormalities and disturbances in reading. In this work, we
      investigated whether eye movement alterations during reading might be already
      present at very early stages of the disease. METHODS: Twenty female and male
      adult patients with the diagnosis of probable AD and 20 age-matched individuals
      with no evidence of cognitive decline participated in the study. Participants
      were seated in front of a 20-inch LCD monitor and single sentences were presented
      on it. Eye movements were recorded with an eye tracker, with a sampling rate of
      1000 Hz and an eye position resolution of 20 arc seconds. RESULTS: Analysis of
      eye movements during reading revealed that patients with early AD decreased the
      amount of words with only one fixation, increased their total number of first-
      and second-pass fixations, the amount of saccade regressions and the number of
      words skipped, compared with healthy individuals (controls). They also reduced
      the size of outgoing saccades, simultaneously increasing fixation duration.
      CONCLUSIONS: The present study shows that patients with mild AD evidenced marked
      alterations in eye movement behavior during reading, even at early stages of the
      disease. Hence, evaluation of eye movement behavior during reading might provide
      a useful tool for a more precise early diagnosis of AD and for dynamical
      monitoring of the pathology.

PMID- 24282225
TI  - Optical coherence tomography as a diagnostic tool for retinal pathologies in
      avian ophthalmology.
AB  - PURPOSE: Optical coherence tomography (OCT) is an established diagnostic tool for
      retinal pathologies in human eyes and has been adapted to small animal models.
      However, there have been only a few attempts to use OCT for examination of avian
      eyes, and little is known about structural details of healthy or pathologically
      affected retinas in living birds. METHODS: We used SD-OCT (high-resolution
      spectral domain OCT) to investigate eyes of various avian species including birds
      of prey. The birds were anesthetized by isoflurane application during OCT
      examination. Eyes of a common buzzard (Buteo buteo) could be used for a
      comparative analysis of OCT images and histologic/immunohistochemical
      examinations. RESULTS: We investigated 45 wild and domestic birds (25 different
      species, 40 g-7.7 kg body mass) without and with diverse pathologic indications
      (e.g., body or head trauma). Animals were generally and ophthalmologically
      examined, and the diagnostic findings of direct ophthalmoscopy and OCT were
      compared. The OCT examination revealed an increased number of animals with
      clinical findings and allowed a detailed assessment of structural changes in
      retinal and choroidal tissue compared to simple direct ophthalmoscopy. Common
      findings were retinal and choroidal degeneration, retinal detachment, choroidal
      schisis, drusen, and drusenoid changes. Histologic and immunohistochemical
      analysis of retinal tissue confirmed the findings of the OCT examination.
      CONCLUSIONS: Spectral domain OCT of eyes in living birds is applicable and useful
      as a diagnostic tool in veterinary clinical practices and for vision research in
      general. Optical coherence tomography improves the quality of the common
      assessment methods in avian ophthalmology, and expands the diagnostic
      possibilities with respect to identification and prognosis of diseases. This will
      be particularly important for hereditary retinal defects, especially of precious
      breeding individuals, or estimation of treatment success in traumatized wild
      birds with the aim of release back into the wild.

PMID- 24282224
TI  - Global motion perception in 2-year-old children: a method for psychophysical
      assessment and relationships with clinical measures of visual function.
AB  - PURPOSE: We developed and validated a technique for measuring global motion
      perception in 2-year-old children, and assessed the relationship between global
      motion perception and other measures of visual function. METHODS: Random dot
      kinematogram (RDK) stimuli were used to measure motion coherence thresholds in
      366 children at risk of neurodevelopmental problems at 24 +/- 1 months of age.
      RDKs of variable coherence were presented and eye movements were analyzed offline
      to grade the direction of the optokinetic reflex (OKR) for each trial. Motion
      coherence thresholds were calculated by fitting psychometric functions to the
      resulting datasets. Test-retest reliability was assessed in 15 children, and
      motion coherence thresholds were measured in a group of 10 adults using OKR and
      behavioral responses. Standard age-appropriate optometric tests also were
      performed. RESULTS: Motion coherence thresholds were measured successfully in 336
      (91.8%) children using the OKR technique, but only 31 (8.5%) using behavioral
      responses. The mean threshold was 41.7 +/- 13.5% for 2-year-old children and 3.3
      +/- 1.2% for adults. Within-assessor reliability and test-retest reliability were
      high in children. Children's motion coherence thresholds were significantly
      correlated with stereoacuity (LANG I & II test, rho = 0.29, P < 0.001; Frisby,
      rho = 0.17, P = 0.022), but not with binocular visual acuity (rho = 0.11, P =
      0.07). In adults OKR and behavioral motion coherence thresholds were highly
      correlated (intraclass correlation = 0.81, P = 0.001). CONCLUSIONS: Global motion
      perception can be measured in 2-year-old children using the OKR. This technique
      is reliable and data from adults suggest that motion coherence thresholds based
      on the OKR are related to motion perception. Global motion perception was related
      to stereoacuity in children.

PMID- 24282226
TI  - Triple combination of siRNAs targeting TGFbeta1, TGFbetaR2, and CTGF enhances
      reduction of collagen I and smooth muscle actin in corneal fibroblasts.
AB  - PURPOSE: Transforming growth factor beta1 (TGFbeta1), TGFbeta receptor
      (TGFbetaR2), and connective tissue growth factor (CTGF) are key regulators of
      fibrosis in the cornea and in other tissues, including liver, skin, and kidney.
      We developed an antifibrotic treatment targeting these three critical scarring
      genes by using a combination of small interfering RNAs (siRNAs) and assessed its
      effect on downstream scarring genes, collagen I, and alpha smooth muscle actin
      (SMA). METHODS: Up to six individual siRNAs for each of the three target gene
      mRNAs were transfected into cultures of rabbit corneal fibroblasts at
      concentrations from 15 to 90 nM. The knockdown of target gene proteins was
      measured by ELISA, and the two most effective siRNAs were tested in dual
      combinations. Knockdown percentages of both individual and dual siRNA
      combinations were analyzed for synergy by using combination index to predict
      "effective" and "ineffective" triple siRNA combinations. Effects of both triple
      siRNA combinations on target and downstream mRNAs were measured by using
      quantitative RT-PCR, and levels of SMA protein were assessed by
      immunohistochemistry. RESULTS: Single and dual siRNA combinations produced a wide
      range of protein knockdown of target genes (5%-80%). The effective triple siRNA
      combination significantly reduced mRNA levels of target genes (>80%) and
      downstream scarring genes (>85%), and of SMA protein (>95%), and significantly
      reduced cell migration without reducing cell viability. CONCLUSIONS: Simultaneous
      targeting of TGFbeta1, TGFbetaR2, and CTGF genes by effective triple siRNA
      combination produced high knockdown of target and downstream scarring genes
      without cell toxicity, which may have clinical applications in reducing corneal
      fibrosis and scarring in other tissues.

PMID- 24282228
TI  - Examining visual field loss in patients in glaucoma clinics during their
      predicted remaining lifetime.
AB  - PURPOSE: To evaluate the proportion of patients in glaucoma clinics progressing
      at rates that would result in visual disability within their expected lifetime.
      METHODS: This retrospective study used visual field (VF) series of at least 3
      years' duration from 3790 UK patients in glaucoma clinics calculating rates of
      loss for each eye using linear regression of mean deviation (MD) over time.
      Residual life expectancies derived from the UK Office of National Statistics
      actuarial tables for each patient were combined with these rates to estimate
      predicted MDs at end of expected lifetime. The proportion of patients projected
      to progress to visual impairment (MD: -14 dB or worse) or statutory blindness
      (MD: -22 dB or worse) in both eyes before end of expected lifetime was
      calculated. RESULTS: Only 3.0% (95% confidence interval [CI] 2.7%-3.4%) of
      patient eyes progressed at faster than -1.5 dB/year (n = 7149 eyes). Of those
      patients with both eyes followed, 5.2% (CI 4.5%-6.0%) were predicted to progress
      to statutory blindness, with a further 10.4% (CI 9.4%-11.4%) reaching visual
      impairment in their lifetime. More than 90% (CI 85.7%-94.3%) of patients
      predicted to progress to statutory blindness, had an MD worse than -6 dB in at
      least one eye at presentation. CONCLUSIONS: This modeling exercise indicates that
      most patients in glaucoma clinics are not at high risk of progressing to
      statutory blindness. The likelihood of patients suffering impairment in their
      lifetimes is linked to VF loss at presentation, which illuminates the importance
      of reliably detecting significant VF defects in primary care.

PMID- 24282227
TI  - Nonpigmented ciliary epithelial cells respond to acetazolamide by a soluble
      adenylyl cyclase mechanism.
AB  - PURPOSE: The nonpigmented ciliary epithelium (NPE) is rich in soluble adenylyl
      cyclase (sAC), a proposed cytoplasmic bicarbonate sensor. Here, we examine the
      contribution of sAC to an increase in cyclic AMP (cAMP) and changes in a key ion
      transporter, H(+)-ATPase, in NPE exposed to acetazolamide, a carbonic anhydrase
      inhibitor (CAI). METHODS: Cyclic AMP was measured by radioimmunoassay in primary
      cultured porcine NPE. The pH-sensitive dye BCECF was used to examine cytoplasmic
      pH regulation. Subcellular protein translocation was examined by Western blot.
      RESULTS: A transient cAMP increase, detectable within minutes of acetazolamide
      treatment, was prevented by KH7, a specific sAC inhibitor. Following 10-minute
      exposure to acetazolamide, the abundance of H(+)-ATPase B1 subunit and sAC was
      doubled in a plasma membrane-rich fraction, suggesting subcellular translocation.
      Similar evidence of H(+)-ATPase translocation was observed in NPE exposed to 8
      Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Consistent with increased
      capacity for proton export, acetazolamide increased the rate of pH recovery from
      acidification. KH7 and bafilomycin A1, an inhibitor of H(+)-ATPase, both
      prevented the stimulatory effect of acetazolamide on pH recovery. In a parallel
      study, H(+)-ATPase abundance was found to be higher in the plasma membrane of
      HEK293 cells that overexpress sAC compared to the normal HEK293 cells. HEK cells
      that overexpress sAC and had higher H(+)-ATPase abundance displayed a faster rate
      of pH recovery and greater sensitivity to KH7. CONCLUSIONS: Acetazolamide
      increases cAMP in a response that involves activation of sAC. Subcellular
      translocation of H(+)-ATPase and an increase in the capacity for proton export by
      acetazolamide-treated NPE cells is a cAMP-dependent response.

PMID- 24282229
TI  - Effect of Ginkgo biloba on visual field and contrast sensitivity in Chinese
      patients with normal tension glaucoma: a randomized, crossover clinical trial.
AB  - PURPOSE: We evaluated the effect of ginkgo biloba extract on visual field defect
      and contrast sensitivity in a Chinese cohort with normal tension glaucoma.
      METHODS: In this prospective, randomized, placebo-controlled crossover study,
      patients newly diagnosed with normal tension glaucoma, either in a tertiary
      glaucoma clinic (n = 5) or in a cohort undergoing routine general physical
      examinations in a primary care clinic (n = 30), underwent two 4-week phases of
      treatment, separated by a washout period of 8 weeks. Randomization determined
      whether ginkgo biloba extract (40 mg, 3 times per day) or placebo (identical
      appearing tablets) was received first. Primary outcomes were change in contrast
      sensitivity and mean deviation on 24-2 SITA standard visual field testing, while
      secondary outcomes included IOP and self-reported adverse events. RESULTS: A
      total of 35 patients with mean age 63.7 (6.5) years were randomized to the ginkgo
      biloba extract-placebo (n = 18) or the placebo-ginkgo biloba extract (n = 17)
      sequence. A total of 28 patients (80.0%, 14 in each group) who completed testing
      did not differ at baseline in age, sex, visual field mean deviation, contrast
      sensitivity, IOP, or blood pressure. Changes in visual field and contrast
      sensitivity did not differ by treatment received or sequence (P > 0.2 for all).
      Power to have detected a difference in mean defect as large as previously
      reported was 80%. CONCLUSIONS: In contrast to some previous reports, ginkgo
      biloba extract treatment had no effect on mean defect or contrast sensitivity in
      this group of normal tension glaucoma patients. (http://www.chictr.org number,
      ChiCTR-TRC-08000724).

PMID- 24282230
TI  - Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by
      two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.
AB  - PURPOSE: Diabetes mellitus has been shown to be associated with and complicated
      by dry eye syndrome. We sought to examine and compare the tear film proteome of
      type 2 diabetic patients with or without dry eye syndrome and normal subjects
      using two-dimensional nano-liquid chromatography coupled with tandem mass
      spectrometry (MS)-based proteomics. METHODS: Tears were collected from eight type
      2 diabetes patients with dry eye syndrome, eight type 2 diabetes patients without
      dry eye syndrome, and eight normal subjects. Tear breakup time (BUT) was
      determined, and tear proteins were prepared and analyzed using two-dimensional
      strong cation-exchange/reversed-phase nano-scale liquid chromatography MS. All
      MS/MS spectra were identified by using SEQUEST against the human International
      Protein Index (IPI) database and the relative abundance of individual proteins
      was assessed by spectral counting. RESULTS: Tear BUT was significantly lower in
      patients with diabetes and dry eye syndrome than in patients with diabetes only
      and normal subjects. Analysis of spectral counts of tear proteins showed that,
      compared to healthy controls, patients with diabetes and dry eye syndrome had
      increased expression of apoptosis-related proteins, like annexin A1, and immunity
      and inflammation-related proteins, including neutrophil elastase 2 and
      clusterin, and glycometabolism-related proteins, like apolipoprotein A-II.
      CONCLUSIONS: Dry eye syndrome in diabetic patients is associated with aberrant
      expression of tear proteins, and the findings could lead to identification of
      novel pathways for therapeutic targeting and new diagnostic markers.

PMID- 24282231
TI  - Biophysical and morphological evaluation of human normal and dry eye meibum using
      hot stage polarized light microscopy.
AB  - PURPOSE: To study melting characteristics and the morphology of human and mouse
      meibum. METHODS: Hot stage cross-polarized light microscopy (HSPM) and
      immunohistochemical approaches were used. RESULTS: Isolated human meibum, and
      meibum of mice (either isolated or within the meibomian ducts of mice), were
      found to be in liquid-crystal state at physiological temperatures. Melting of
      both types of meibum started at approximately 10 degrees C and was completed at
      approximately 40 degrees C. Melting curves of isolated meibum and meibum inside
      the meibomian ducts were multiphasic with at least two or three clearly defined
      phase transition temperatures, typically at approximately 12 +/- 2 degrees C
      (minor transition), 21 +/- 3 degrees C, and 32 +/- 3 degrees C, regardless the
      source of meibum. Melting was highly cooperative in nature. Samples of abnormal
      human meibum collected from dry eye patients with meibomian gland dysfunction
      often showed an increased presence of nonlipid, nonmelting, nonbirefringent,
      chloroform-insoluble inclusions of a protein nature. The inclusions were
      positively stained for cytokeratins. The presence of these inclusions was
      semiquantitatively characterized using a newly proposed 0 to 4 scale. In the
      presence of large amounts of these inclusions, melting characteristics of meibum
      and its structural integrity were altered. CONCLUSIONS: HSPM is an effective tool
      that is suitable for biophysical and morphological evaluation of meibum.
      Morphological properties and melting characteristics of human meibum were found
      to be similar to those of mice. Abnormal meibum of many dry eye patients
      contained large quantities of nonlipid, protein-like inclusions, which were
      routinely absent in meibum of normal controls.

PMID- 24282232
TI  - Combining spectral domain optical coherence tomography structural parameters for
      the diagnosis of glaucoma with early visual field loss.
AB  - PURPOSE: To create a multivariable predictive model for glaucoma with early
      visual field loss using a combination of spectral-domain optical coherence
      tomography (SD-OCT) parameters, and to compare the results with single variable
      models. METHODS: Two hundred fifty-three subjects (149 healthy controls and 104
      with early glaucoma) underwent optic disc and macular scanning using SD-OCT in
      one randomly selected eye per subject. Sixteen parameters (rim area, cup-to-disc
      area ratio, vertical cup-to-disc diameter ratio, average and quadrant RNFL
      thicknesses, average, minimum, and sectoral ganglion cell inner-plexiform layer
      [GCIPL] thicknesses) were collected and submitted to an exploratory factor
      analysis (EFA) followed by logistic regression with the backward elimination
      variable selection technique. Area under the curve (AUC) of the receiver
      operating characteristic (ROC), sensitivity, specificity, Akaike's information
      criterion (AIC), predicted probability, prediction interval length (PIL), and
      classification rates were used to determine the performances of the univariable
      and multivariable models. RESULTS: The multivariable model had an AUC of 0.995
      with 98.6% sensitivity, 96.0% specificity, and an AIC value of 43.29. Single
      variable models yielded AUCs of 0.943 to 0.987, sensitivities of 82.6% to 95.7%,
      specificities of 88.0% to 94.0%, and AICs of 113.16 to 59.64 (smaller is
      preferred). The EFA logistic regression model correctly classified 91.67% of
      cases with a median PIL of 0.050 in the validation set. Univariable models
      correctly classified 80.62% to 90.48% of cases with median PILs 1.9 to 3.0 times
      larger. CONCLUSIONS: The multivariable model was successful in predicting
      glaucoma with early visual field loss and outperformed univariable models in
      terms of AUC, AIC, PILs, and classification rates.

PMID- 24282233
TI  - Comparison of macular choroidal thickness in adult onset foveomacular vitelliform
      dystrophy and age-related macular degeneration.
AB  - PURPOSE: To compare macular choroidal thickness (MCT) in eyes with adult onset
      foveomacular vitelliform dystrophy (AOFVD) and eyes with AMD. METHODS: Five
      groups of 38 eyes each were included in a prospective, observational, comparative
      study: AOFVD eyes with fluid accumulation; AOFVD fellow eyes without fluid (early
      stage); advanced exudative (wet) AMD; advanced dry AMD; and healthy normal eyes.
      All study eyes underwent a comprehensive ophthalmologic examination. Macular
      choroidal thickness was measured using enhanced depth imaging optical coherence
      tomography (EDI-OCT). RESULTS: Subfoveal choroidal thickness (SFCT) in AOFVD with
      subretinal fluid (325.66 +/- 85.98 MUm) was significantly (P < 0.001) thicker
      compared with that in exudative AMD (158.55 +/- 57.87 MUm) and in dry AMD (157.53
      +/- 67.08 MUm). Also, in AOFVD, the choroid was significantly (P = 0.001) thicker
      than that in the normal group (255.87 +/- 87.46 MUm). However, in AOFVD, there
      was no significant difference (P = 0.69) between the SFCT in the study eye and in
      the fellow eye (317.66 +/- 90.04 MUm). The choroidal thickness at each of the
      other 12 measured points showed similar results. CONCLUSIONS: This study
      demonstrates choroidal thickening in AOFVD in contrast with the choroidal
      thinning observed in advanced AMD. These findings suggest that the pathogenic
      mechanisms in AOFVD are different from those in exudative AMD. Choroidal
      thickness measurement could help differentiate the challenging diagnosis between
      exudative AMD and the advanced stage of AOFVD (with fluid accumulation but
      without choroidal neovascularization).

PMID- 24282234
TI  - Developmental lineage priming in Dictyostelium by heterogeneous Ras activation.
AB  - In cell culture, genetically identical cells often exhibit heterogeneous
      behavior, with only 'lineage primed' cells responding to differentiation inducing
      signals. It has recently been proposed that such heterogeneity exists during
      normal embryonic development to allow position independent patterning based on
      'salt and pepper' differentiation and sorting out. However, the molecular basis
      of lineage priming and how it leads to reproducible cell type proportioning are
      poorly understood. To address this, we employed a novel forward genetic approach
      in the model organism Dictyostelium discoideum. These studies reveal that the Ras
      GTPase regulator gefE is required for normal lineage priming and salt and pepper
      differentiation. This is because Ras-GTPase activity sets the intrinsic response
      threshold to lineage specific differentiation signals. Importantly, we show that
      although gefE expression is uniform, transcription of its target, rasD, is both
      heterogeneous and dynamic, thus providing a novel mechanism for heterogeneity
      generation and position-independent differentiation. DOI:
      http://dx.doi.org/10.7554/eLife.01067.001. 

PMID- 24282235
TI  - Survival of the fattest.
AB  - Experiments on the social amoeba Dictyostelium discoideum show that the origins
      of lineage bias in this system lie in the nutritional history of individual
      cells. Clues to the molecular basis for this process suggest similar forces may
      be at work in early mammalian development. 

PMID- 24282237
TI  - Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic
      cardiac muscle.
AB  - In fibroblasts, large Ca transients activate massive endocytosis (MEND) that
      involves membrane protein palmitoylation subsequent to mitochondrial permeability
      transition pore (PTP) openings. Here, we characterize this pathway in cardiac
      muscle. Myocytes with increased expression of the acyl transferase, DHHC5, have
      decreased Na/K pump activity. In DHHC5-deficient myocytes, Na/K pump activity and
      surface area/volume ratios are increased, the palmitoylated regulatory protein,
      phospholemman (PLM), and the cardiac Na/Ca exchanger (NCX1) show greater surface
      membrane localization, and MEND is inhibited in four protocols. Both electrical
      and optical methods demonstrate that PTP-dependent MEND occurs during
      reoxygenation of anoxic hearts. Post-anoxia MEND is ablated in DHHC5-deficient
      hearts, inhibited by cyclosporine A (CsA) and adenosine, promoted by
      staurosporine (STS), reduced in hearts lacking PLM, and correlates with impaired
      post-anoxia contractile function. Thus, the MEND pathway appears to be
      deleterious in severe oxidative stress but may constitutively contribute to
      cardiac sarcolemma turnover in dependence on metabolic stress. DOI:
      http://dx.doi.org/10.7554/eLife.01295.001. 

PMID- 24282236
TI  - Massive endocytosis triggered by surface membrane palmitoylation under
      mitochondrial control in BHK fibroblasts.
AB  - Large Ca transients cause massive endocytosis (MEND) in BHK fibroblasts by
      nonclassical mechanisms. We present evidence that MEND depends on mitochondrial
      permeability transition pore (PTP) openings, followed by coenzyme A (CoA)
      release, acyl CoA synthesis, and membrane protein palmitoylation. MEND is blocked
      by inhibiting mitochondrial Ca uptake or PTP openings, depleting fatty acids,
      blocking acyl CoA synthesis, metabolizing CoA, or inhibiting palmitoylation. It
      is triggered by depolarizing mitochondria or promoting PTP openings. After
      mitochondrial MEND blockade, MEND is restored by cytoplasmic acyl CoA or CoA.
      MEND is blocked by siRNA knockdown of the plasmalemmal acyl transferase, DHHC5.
      When acyl CoA is abundant, transient H2O2 oxidative stress or PKC activation
      initiates MEND, but the immediate presence of H2O2 prevents MEND. The PTP
      inhibitor, NIM811, significantly increases plasmalemma in normally growing cells.
      Thus, the MEND pathway may contribute to constitutive as well as pathological
      plasmalemma turnover in dependence on mitochondrial stress signaling. DOI:
      http://dx.doi.org/10.7554/eLife.01293.001. 

PMID- 24282238
TI  - The mother of all endocytosis.
AB  - Massive endocytosis is initiated by a series of steps that involve a sudden
      influx of calcium ions, changes in mitochondria, and modification of surface
      proteins by lipids. A better understanding of this process could lead to new
      approaches to reducing the tissue damage that is caused by heart attacks. 

PMID- 24282239
TI  - ProANP plasma measurement predicts all-cause mortality in acutely hospitalised
      patients: a cohort study.
AB  - IMPORTANCE: The association of natriuretic peptide measurement with all-cause
      mortality in a broad selection of acutely admitted patients has not yet been
      examined. OBJECTIVE: To test the risk association between pro-atrial natriuretic
      peptide (ANP) and short-term and long-term mortality and its predictive value in
      acutely hospitalised patients and compare this to N-terminal B-type natriuretic
      peptide (NT-proBNP). DESIGN, SETTING AND PATIENTS: Participants were selected
      from the Copenhagen Hospital Heart Failure Study (n=3644). Medical history,
      satisfactory echocardiography and blood samples were available on 2193
      participants in 1998-1999 where NT-proBNP was measured. Vital status after
      discharge was obtained from national central data registers. A total of 1337
      participants with eligible blood samples were selected in 2010-2011 for proANP
      measurement. Among these, 1255 (94%) were acutely hospitalised in 1998-1999. MAIN
      OUTCOME MEASURE(S): 1-year and long-term mortality. RESULTS: Median follow-up
      period was 11.5 years. At the end of follow-up, 926 patients had died, 239 during
      the first year. ProANP quartiles to 2-4 (median proANP levels 594 pmol/L, 990
      pmol/L and 2052 pmol/L, respectively) associated with a stepwise increase in risk
      of 1-year and long-term mortality compared to the first quartile (336 pmol/L) in
      multivariable adjusted Cox proportional regression models (HR 1.53 95% CI 1.30 to
      1.81 and HR 1.26 95% CI 1.17 to 1.36, respectively). An addition of NT-proBNP
      attenuated proANP's association with mortality in the models (HR 1.24 95% CI 1.01
      to 1.53 and 1.14 95% CI 1.03 to 1.26, respectively). The increased risk was
      observed in participants with the highest proANP levels (fourth quartile).
      Similar results were observed in subgroups of participants with no evidence of
      cardiovascular disease (CVD). ProANP in quartiles improved discrimination when
      added to traditional risk factors in prediction models for 1-year (integrated
      discrimination improvement (IDI) 0.141 95% CI 0.085 to 0.197; C-index 0.753 95%
      CI 0.724 to 0.783, P for improvement 0.003) and long-term mortality (IDI 0.053
      95% CI 0.032 to 0.074; C-index 0.736 95% CI 0.720 to 0.752, P for improvement
      <0.001) with similar results in subgroups. Discrimination was best in a combined
      model with proANP as well as NT-proBNP included. CONCLUSIONS AND RELEVANCE: High
      plasma proANP concentrations are associated with and predict short-term and long
      term all-cause mortality in acutely hospitalised patients irrespective of CVD
      status at admission.

PMID- 24282240
TI  - Reduction in myocardial infarction admissions in Liverpool after the smoking ban:
      potential socioeconomic implications for policymaking.
AB  - OBJECTIVES: To analyse the trends and trend changes in myocardial infraction (MI)
      and coronary heart disease (CHD) admissions, to investigate the effects of the
      2007 smoke-free legislation on these trends, and to consider the policy
      implications of any findings. DESIGN SETTING: Liverpool (city), UK. PARTICIPANTS:
      Hospital episode statistics data on all 56 995 admissions for CHD in Liverpool
      between 2004 and 2012 (International Classification of Diseases codes I20-I25
      coded as an admission diagnosis within the defined dates). PRIMARY AND SECONDARY
      OUTCOME MEASURES: Trend gradient and change points (by trend regressions
      analysis) in age-standardised MI admissions in Liverpool between 2004 and 2012;
      by sex and by socioeconomic status. Secondary analysis on CHD admissions.
      RESULTS: A significant and sustained reduction was seen in MI admissions in
      Liverpool beginning within 1 year of the smoking ban. Comparing 2005/2006 and
      2010/2011, the age-adjusted rates for MI admissions fell by 42% (39-45%) (41.6%
      in men and by 42.6% in women). Trend analysis shows that this is significantly
      greater than the background trend of decreasing admissions. These reductions
      appeared consistent across all socioeconomic groups. Interestingly, admission
      rates for total CHD (including mild to severe angina) increased by 10% (8-12%).
      CONCLUSIONS: A dramatic reduction in MI admissions in Liverpool has been observed
      coinciding with the smoking ban in 2007. Furthermore, the benefits were apparent
      across the socioeconomic spectrum. Health inequalities were not affected and may
      even have been reduced. The rapid effects observed with this top-down,
      environmental policy may further increase its value to policymakers.

PMID- 24282241
TI  - The impact of neurological disorders on the risk for falls in the community
      dwelling elderly: a case-controlled study.
AB  - OBJECTIVES: Owing to a lack of data, our aim was to evaluate and compare the
      impact of various common neurological diseases on the risk for falls in
      independent community dwelling senior citizens. DESIGN: Prospective case
      controlled study. SETTING: General hospital. PARTICIPANTS: Of 298 consecutive
      patients and 214 controls enrolled, 228 patients (aged 74.5+/-7.8; 61% women) and
      193 controls (aged 71.4+/-6.8; 63% women) were included. The exclusion criteria
      were as follows: for patients, severe disability, disabling general condition or
      severe cognitive impairment; for controls, any history of neurological disorders
      or disabling medical conditions; and for both, age below 60 years. A matching
      process led to 171 age-matched and gender-matched pairs of neurological patients
      and healthy controls. MAIN OUTCOME MEASURES: A 1-year incidence of falls based on
      patients' 12-month recall; motor and non-motor function tests to detect
      additional risk factors. RESULTS: 46% of patients and 16% of controls fell at
      least once a year. Patients with stroke (89%), Parkinson's disease (77%),
      dementia (60%) or epilepsy (57%) had a particularly high proportion of fallers,
      but even subgroups of patients with the least fall-associated neurological
      diseases like tinnitus (30%) and headache (28%) had a higher proportion of
      fallers than the control group. Neuropathies, peripheral nerve lesions and
      Parkinson's disease were predisposing to recurrent falls. A higher number of
      neurological comorbidities (p<0.001), lower Barthel Index values (p<0.001), lower
      Activities-Specific Balance Confidence scores (p<0.001) and higher Center of
      Epidemiological Studies Depression scores (p<0.001) as well as higher age
      (p<0.001) and female gender (p=0.003) proved to further increase the risk of
      falls. CONCLUSIONS: Medical practitioners, allied health professionals and carers
      should be aware that all elderly neurological patients seen in outpatient
      settings are potentially at high risk for falls; they should query them routinely
      about previous falls and fall risks and advise them on preventive strategies.

PMID- 24282242
TI  - Attitudes towards smoking restrictions and tobacco advertisement bans in Georgia.
AB  - OBJECTIVES: This study aims to provide data on a public level of support for
      restricting smoking in public places and banning tobacco advertisements. DESIGN:
      A nationally representative multistage sampling design, with sampling strata
      defined by region (sampling quotas proportional to size) and substrata defined by
      urban/rural and mountainous/lowland settlement, within which census enumeration
      districts were randomly sampled, within which households were randomly sampled,
      within which a randomly selected respondent was interviewed. SETTING: The country
      of Georgia, population 4.7 million, located in the Caucasus region of Eurasia.
      PARTICIPANTS: One household member aged between 13 and 70 was selected as
      interviewee. In households with more than one age-eligible person, selection was
      carried out at random. Of 1588 persons selected, 14 refused to participate and
      interviews were conducted with 915 women and 659 men. OUTCOME MEASURES:
      Respondents were interviewed about their level of agreement with eight possible
      smoking restrictions/bans, used to calculate a single dichotomous (agree/do not
      agree) opinion indicator. The level of agreement with restrictions was analysed
      in bivariate and multivariate analyses by age, gender, education, income and
      tobacco use status. RESULTS: Overall, 84.9% of respondents indicated support for
      smoking restrictions and tobacco advertisement bans. In all demographic segments,
      including tobacco users, the majority of respondents indicated agreement with
      restrictions, ranging from a low of 51% in the 13-25 age group to a high of 98%
      in the 56-70 age group. Logistic regression with all demographic variables
      entered showed that agreement with restrictions was higher with age, and was
      significantly higher among never smokers as compared to daily smokers.
      CONCLUSIONS: Georgian public opinion is normatively supportive of more stringent
      tobacco-control measures in the form of smoking restrictions and tobacco
      advertisement bans.

PMID- 24282243
TI  - The cost-effectiveness of a structured education pulmonary rehabilitation
      programme for chronic obstructive pulmonary disease in primary care: the PRINCE
      cluster randomised trial.
AB  - OBJECTIVE: To assess the cost-effectiveness of a structured education pulmonary
      rehabilitation programme (SEPRP) for chronic obstructive pulmonary disease (COPD)
      relative to usual practice in primary care. The programme consisted of group
      based sessions delivered jointly by practice nurses and physiotherapists over 8
      weeks. DESIGN: Cost-effectiveness and cost-utility analysis alongside a cluster
      randomised controlled trial. SETTING: 32 general practices in Ireland.
      PARTICIPANTS: 350 adults with COPD, 69% of whom were moderately affected.
      INTERVENTIONS: Intervention arm (n=178) received a 2 h group-based SEPRP session
      per week over 8 weeks delivered jointly by a practice nurse and physiotherapist
      at the practice surgery or nearby venue. The control arm (n=172) received the
      usual practice in primary care. MAIN OUTCOME MEASURES: Incremental costs, Chronic
      Respiratory Questionnaire (CRQ) scores, quality-adjusted life years (QALYs)
      gained estimated using the generic EQ5D instrument, and expected cost
      effectiveness at 22 weeks trial follow-up. RESULTS: The intervention was
      associated with an increase of ?944 (95% CIs 489 to 1400) in mean healthcare cost
      and ?261 (95% CIs 226 to 296) in mean patient cost. The intervention was
      associated with a mean improvement of 1.11 (95% CIs 0.35 to 1.87) in CRQ Total
      score and 0.002 (95% CIs -0.006 to 0.011) in QALYs gained. These translated into
      incremental cost-effectiveness ratios of ?850 per unit increase in CRQ Total
      score and ?472 000 per additional QALY gained. The probability of the
      intervention being cost-effective at respective threshold values of ?5000, ?15
      000, ?25 000, ?35 000 and ?45 000 was 0.980, 0.992, 0.994, 0.994 and 0.994 in the
      CRQ Total score analysis compared to 0.000, 0.001, 0.001, 0.003 and 0.007 in the
      QALYs gained analysis. CONCLUSIONS: While analysis suggests that SEPRP was cost
      effective if society is willing to pay at least ?850 per one-point increase in
      disease-specific CRQ, no evidence exists when effectiveness was measured in QALYS
      gained. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52 403 063.

PMID- 24282244
TI  - Capturing intraoperative process deviations using a direct observational
      approach: the glitch method.
AB  - OBJECTIVES: To develop a sensitive, reliable tool for enumerating and evaluating
      technical process imperfections during surgical operations. DESIGN: Prospective
      cohort study with direct observation. SETTING: Operating theatres on five sites
      in three National Health Service Trusts. PARTICIPANTS: Staff taking part in
      elective and emergency surgical procedures in orthopaedics, trauma, vascular and
      plastic surgery; including anaesthetists, surgeons, nurses and operating
      department practitioners. OUTCOME MEASURES: Reliability and validity of the
      glitch count method; frequency, type, temporal pattern and rate of glitches in
      relation to site and surgical specialty. RESULTS: The glitch count has construct
      and face validity, and category agreement between observers is good (kappa=0.7).
      Redundancy between pairs of observers significantly improves the sensitivity over
      a single observation. In total, 429 operations were observed and 5742 glitches
      were recorded (mean 14 per operation, range 0-83). Specialty-specific glitch
      rates varied from 6.9 to 8.3/h of operating (ns). The distribution of glitch
      categories was strikingly similar across specialties, with distractions the
      commonest type in all cases. The difference in glitch rate between specialty
      teams operating at different sites was larger than that between specialties
      (range 6.3-10.5/h, p<0.001). Forty per cent of glitches occurred in the first
      quarter of an operation, and only 10% occurred in the final quarter. CONCLUSIONS:
      The glitch method allows collection of a rich dataset suitable for analysing the
      changes following interventions to improve process safety, and appears reliable
      and sensitive. Glitches occur more frequently in the early stages of an
      operation. Hospital environment, culture and work systems may influence the
      operative process more strongly than the specialty.

PMID- 24282245
TI  - Urban-rural differentials in the factors associated with exposure to second-hand
      smoke in India.
AB  - OBJECTIVES: This study aims to investigate the role of different factors
      associated with exposure to second-hand smoke (SHS) in the workplace and home in
      the urban and rural areas of India. DESIGN: Secondary analysis of the data from
      the Global Adult Tobacco Survey conducted in 2009-2010. SETTING AND PARTICIPANTS:
      Data were analysed from 32 738 rural and 23 202 urban non-smokers at home and
      4809 rural and 6227 urban non-smokers in the workplace in India. OUTCOMES AND
      METHODS: We used two measures of SHS: exposure to SHS at home and exposure to SHS
      in the workplace. SHS exposure at home is estimated for non-smokers who reported
      anyone smoking inside his/her home. Exposure to SHS in the workplace is estimated
      for non-smokers who reported anyone smoking in the workplace in the past 30 days
      before the survey. Statistical techniques such as chi(2) test, logistic
      regression and discriminant function analysis were used. RESULTS: The results
      showed that SHS exposure in the workplace and home is higher in the rural areas
      than in the urban areas. As compared with men, women are significantly more
      likely to be exposed to SHS at home (OR=1.20, 95% CI 1.10 to 1.30) in the rural
      areas, and less likely at the workplace in the urban areas (OR=0.49, 95% CI 0.40
      to 0.59). Education and region are significant predictors of exposure levels to
      SHS at home and the workplace in the rural and urban areas. The knowledge of
      number of smoking-related hazards significantly discriminates the SHS exposure in
      the rural workplace. SHS exposure at home is most affected by region in the rural
      areas and education in the urban areas. CONCLUSIONS: The factors which affect SHS
      exposure differ in the rural and urban areas of India. The study concludes that
      the risk of getting exposed to SHS at home and the workplace among non-smokers is
      higher in the rural areas of the country.

PMID- 24282246
TI  - Primary Sjogren's syndrome 1976-2005 and associated interstitial lung disease: a
      population-based study of incidence and mortality.
AB  - OBJECTIVE: A very few studies describe the epidemiology of primary Sjogren's
      syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies
      widely depending on the detection method employed, and consists mainly of various
      forms of airways disease. We aimed to evaluate the incidence and mortality of pSS
      and of lung disease in pSS, focusing on interstitial lung disease (ILD). METHODS:
      A population-based incidence cohort of patients diagnosed with pSS in 1976-2005
      was assembled. Diagnosis was based on the 2002 American-European Consensus Group
      criteria for pSS. Cumulative incidence adjusted for the competing risk of death
      was estimated. A Cox model with a time-dependent covariate was used to determine
      the incidence and the standardised mortality HR of pSS. RESULTS: 85 patients with
      pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS
      was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age
      at pSS diagnosis (18-44 years: 2.1/100 000 vs >=75 years: 12.3/100 000).
      Standardised mortality ratio in pSS compared with the general population was
      0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were
      identified (mean age 58.1 years; 91% women). Among patients with pSS without
      prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (+/-3%)
      at 1 year after diagnosis of pSS and increased to 20% (+/-4%) by 5 years after
      pSS. The development of lung disease in pSS was associated with poor survival (HR
      2.16; 95% CI 0.99 to 4.74). CONCLUSIONS: pSS incidence seems to be almost the
      same as was reported in a previous study conducted among Olmsted County Minnesota
      population. Survival among patients with pSS and general population does not
      differ substantially. However, patients with pSS who have ILD likely have
      increased premature mortality.

PMID- 24282247
TI  - Effect of exercise on abdominal fat loss in men and women with and without type 2
      diabetes.
AB  - OBJECTIVE: To examine the effect of exercise on abdominal adipose tissue in
      adults with and without type 2 diabetes mellitus (T2DM). DESIGN: Post hoc
      analysis of two randomised controlled trials. SETTING: Outpatient secondary
      prevention programme in Baltimore, Maryland, USA. PARTICIPANTS: 97 men and women
      with prehypertension, stage 1 or medically controlled hypertension. 49% of the
      sample was also diagnosed with T2DM. INTERVENTION: All participants completed a
      26-week (6.5 months) supervised aerobic and resistance exercise programme
      following American College of Sports Medicine guidelines. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The main outcomes in this post hoc analysis were total
      abdominal adipose tissue (TAT), subcutaneous adipose tissue (SAT) and visceral
      adipose tissue (VAT) measured by MRI. Secondary outcomes were to determine
      whether the magnitude of abdominal fat change differed by diabetes status in men
      and women and to identify the predictors of change in abdominal fat distribution
      with exercise. RESULTS: Overall, participants (mean age 61+/-6 years; 45% women)
      significantly improved peak oxygen uptake by 15% (p<0.01) and reduced weight by
      2% (p<0.01). No change in SAT was observed after training. The reduction in VAT
      following exercise was attenuated in participants with T2DM (-3%) compared with
      participants who were non-T2DM (-18%, p<0.001 for the difference in change). The
      magnitude of VAT loss was associated with a decrease in body weight (r=0.50,
      p<0.001). After adjustment for weight change using regression analysis, diabetes
      status remained an independent predictor of the change in VAT. CONCLUSIONS:
      Although participants with and without T2DM attained an exercise training effect
      as evidenced by increased fitness, VAT was unchanged in T2DM compared to those
      without T2DM, suggesting that these individuals may be resistant to this
      important benefit of exercise. The strategies for reducing cardiovascular disease
      risk in T2DM may be most effective when they include a weight loss component.
      CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov Registry NCT00212303.

PMID- 24282248
TI  - Letrozole, berberine, or their combination for anovulatory infertility in women
      with polycystic ovary syndrome: study design of a double-blind randomised
      controlled trial.
AB  - INTRODUCTION: Letrozole is being used as an alternative to clomiphene citrate in
      women with polycystic ovary syndrome (PCOS) requiring ovulation induction.
      Berberine, a major active component of Chinese herbal medicine rhizoma coptidis,
      has been used to improve insulin resistance to facilitate ovulation induction in
      women with PCOS but there is no study reporting the live birth or its potential
      as a complementary treatment to letrozole. We aim to determine the efficacy of
      letrozole with or without berberine in achieving live births among 660 infertile
      women with PCOS in Mainland China. METHODS AND ANALYSIS: This study is a
      multicentre randomised, double-blind trial. The randomisation scheme is
      coordinated through the central mechanism and stratified by the participating
      site. Participants are randomised into one of the three treatment arms: (1)
      letrozole and berberine, (2) letrozole and berberine placebo, or (3) letrozole
      placebo and berberine. Berberine is administered three times a day (1.5 g/day)
      for up to 24 weeks, starting on day 1 after a spontaneous period or a withdrawal
      bleeding. Either letrozole or letrozole placebo 2.5 mg is given daily from day 3
      to day 7 of the first three cycles and the dose is increased to 5 mg/day in the
      last three cycles, if not pregnant. The primary hypothesis is that the
      combination of berberine and letrozole results in a significantly higher live
      birth rate than letrozole or berberine alone. ETHICS AND DISSEMINATION: The study
      was approved by the ethics committee of the First Affiliated Hospital of
      Heilongjiang University of Chinese Medicine. Study findings will be disseminated
      through peer-reviewed publications and conference presentations. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT01116167.

PMID- 24282249
TI  - The CopenHeartSF trial--comprehensive sexual rehabilitation programme for male
      patients with implantable cardioverter defibrillator or ischaemic heart disease
      and impaired sexual function: protocol of a randomised clinical trial.
AB  - INTRODUCTION: Sexuality is an important part of people's physical and mental
      health. Patients with heart disease often suffer from sexual dysfunction. Sexual
      dysfunction has a negative impact on quality of life and well-being in persons
      with heart disease, and sexual dysfunction is associated with anxiety and
      depression. Treatment and care possibilities seem to be lacking. Studies indicate
      that non-pharmacological interventions such as exercise training and
      psychoeducation possess the potential of reducing sexual dysfunction in patients
      with heart disease. The CopenHeartSF trial will investigate the effect of a
      comprehensive sexual rehabilitation programme versus usual care. METHODS AND
      ANALYSIS: CopenHeartSF is an investigator-initiated randomised clinical
      superiority trial with blinded outcome assessment, with 1:1 central randomisation
      to sexual rehabilitation plus usual care versus usual care alone. Based on sample
      size calculations, 154 male patients with impaired sexual function due to
      implantable cardioverter defibrillator or ischaemic heart disease will be
      included from two university hospitals in Denmark. All patients receive usual
      care and patients allocated to the experimental intervention group follow a 12
      week sexual rehabilitation programme consisting of an individualised exercise
      programme and psychoeducative consultation with a specially trained nurse. The
      primary outcome is sexual function measured by the International Index of
      Erectile Function. The secondary outcome measure is psychosocial adjustment to
      illness by the Psychosocial Adjustment to Illness Scale, sexual domain. A number
      of explorative analyses will also be conducted. ETHICS AND DISSEMINATION:
      CopenHeartSF is approved by the regional ethics committee (no H-4-2012-168) and
      the Danish Data Protection Agency (no 2007-58-0015) and is performed in
      accordance with good clinical practice and the Declaration of Helsinki in its
      latest form. REGISTRATION: Clinicaltrials.gov identifier: NCT01796353.

PMID- 24282250
TI  - Age-dependent decline of association between obesity and coronary heart disease:
      a cohort study in a remote Australian Aboriginal community.
AB  - OBJECTIVE: To determine whether the association between obesity and coronary
      heart disease (CHD) in Aboriginal adults depends on age. DESIGN, SETTING AND
      PARTICIPANTS: A cohort study with up to 20 years of follow-up of 849 participants
      aged 18-76 years in a remote Aboriginal community in the Northern Territory of
      Australia. MAIN OUTCOME MEASURES: Newly diagnosed CHD cases were identified
      through hospital records according to ICD codes during the follow-up period. Cox
      proportional hazard model was used to assess whether the association between
      obesity and CHD depends on age. RESULTS: During the follow-up period, 171
      participants were diagnosed with CHD. On an average, the incidence rate of CHD
      increased with the increasing baseline BMI, 11.3%, 16.3% and 20.2% for normal
      weight, overweight and obese groups, respectively. HR of CHD for obesity were 2.6
      (95% CI 1.1to 6.3), 1.2 (0.7 to 2.0) and 0.5 (0.1 to 2.1) for those <40, 40-59
      and 60+ years, respectively. HRs corresponding to 1 SD increase in BMI were 1.4
      (1.0 to 2.0), 1.2 (1.0 to 1.5) and 0.8 (0.5 to 1.2) for those <40, 40-59 and 60+
      years, respectively. The interaction terms between age and BMI as category
      variables or as a continuous variable were statistically significant.
      CONCLUSIONS: The association between obesity and CHD is stronger for younger
      adults than for older adults in Aboriginal Australians in the remote community.
      Our findings suggest that weight control efforts may produce more beneficial
      effects in CHD prevention in young adults than in older adults.

PMID- 24282255
TI  - eRapa restores a normal life span in a FAP mouse model.
AB  - Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in
      familial adenomatous polyposis (FAP), which confers an extremely high risk for
      colon cancer. Apc(Min/+) mice exhibit multiple intestinal neoplasia (MIN) that
      causes anemia and death from bleeding by 6 months. Mechanistic target of
      rapamycin complex 1 (mTORC1) inhibitors were shown to improve Apc(Min/+) mouse
      survival when administered by oral gavage or added directly to the chow, but
      these mice still died from neoplasia well short of a natural life span. The
      National Institute of Aging Intervention Testing Program showed that enterically
      targeted rapamycin (eRapa) extended life span for wild-type genetically
      heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized
      that eRapa would be effective in preventing neoplasia and extend survival of
      Apc(Min/+) mice. We show that eRapa improved survival of Apc(Min/+) mice in a
      dose-dependent manner. Remarkably, and in contrast to previous reports, most of
      the Apc(Min/+) mice fed 42 parts per million eRapa lived beyond the median life
      span reported for wild-type syngeneic mice. Furthermore, chronic eRapa did not
      cause detrimental immune effects in mouse models of cancer, infection, or
      autoimmunity, thus assuaging concerns that chronic rapamycin treatment suppresses
      immunity. Our studies suggest that a novel formulation (enteric targeting) of a
      well-known and widely used drug (rapamycin) can dramatically improve its efficacy
      in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective
      cancer preventatives for people with FAP without suppressing the immune system,
      thus reducing the dependency on surgery as standard therapy.

PMID- 24282256
TI  - Regular aspirin use and risk of multiple myeloma: a prospective analysis in the
      health professionals follow-up study and nurses' health study.
AB  - Multiple myeloma is a lethal malignancy with an unknown etiology and no
      prevention strategy. Aspirin inhibits several pathways mediated by NF-kappaB, COX
      2, or their targets that are important in multiple myeloma pathogenesis. We
      conducted prospective analyses in the Health Professionals Follow-up Study and
      Nurses' Health Study cohorts to examine whether regular aspirin use influences
      multiple myeloma risk. We used biennially updated data to characterize aspirin
      use from baseline through a cancer diagnosis, death, or 2008. We applied a 4-year
      lag in exposure classification to diminish the influence of preclinical multiple
      myeloma on aspirin use habits. We obtained HRs and 95% confidence intervals (CI)
      from multivariable proportional hazard models to assess the association of
      aspirin use with multiple myeloma risk. We tested for trend across increasing
      quantity and duration of use. During 2,395,458 person-years, we confirmed 328
      incident multiple myeloma diagnoses, including 265 with prospective information
      on typical aspirin dose and frequency. Participants with a cumulative average of
      >=5 adult strength (325 mg) tablets per week had a 39% lower multiple myeloma
      risk than nonusers (HR; 95% CI, 0.61, 0.39-0.94; tablets per week, Ptrend =
      0.06). Persons with >=11 years of continuous regular aspirin use also had a lower
      multiple myeloma risk (HR; 95% CI, 0.63, 0.41-0.95; duration, Ptrend = 0.17). The
      associations appeared stronger in men than in women, possibly reflecting gender
      differences in aspirin use patterns. This prospective study of aspirin use and
      multiple myeloma supports an etiologic role for aspirin-inhibited (i.e., NF
      kappaB- or COX-2 mediated) pathways. The utility of aspirin for multiple myeloma
      chemoprevention warrants further evaluation.

PMID- 24282257
TI  - Providing a safe environment for dental care in an era of infectious diseases.

PMID- 24282258
TI  - White-spot lesions.

PMID- 24282259
TI  - Authors' response.

PMID- 24282260
TI  - Statistics.

PMID- 24282261
TI  - Editor's note.

PMID- 24282262
TI  - The need for better studies to assess the safety of providing dental care for
      medically complex patients.

PMID- 24282263
TI  - Hepatitis C virus: an overview for dental health care providers.
AB  - BACKGROUND: and Overview. Changes in the science of hepatitis C virus (HCV)
      infection and transmission in a private dental practice provide an opportunity to
      update dental health care providers about this pathogen. The authors' aims in
      this review were to create awareness of health care- associated transmission of
      hepatitis C and provide an update on the changes in testing and treatment. The
      authors include data from population-based epidemiologic surveys, clinical
      practice guidelines, surveillance reports and practice protocols. RESULTS: In the
      United States, the elevated prevalence of chronic HCV infection among baby
      boomers-people born during the period from 1945 through 1965-led the Centers for
      Disease Control and Prevention to release new national screening guidelines. The
      authors summarize information about the natural history and epidemiology of
      hepatitis C and describe the new guidelines and novel treatment options. In
      addition, the authors provide an overview of how outbreaks of health care
      associated HCV are detected and prevented. Practical Implications. Because dental
      health care professionals likely will treat people with current infection,
      education in the current science of HCV infection is useful.

PMID- 24282264
TI  - Quality assessment of systematic reviews on alveolar ridge preservation.
AB  - BACKGROUND: The authors conducted a study to assess the quality of systematic
      reviews (SRs) published on the topic of alveolar ridge preservation (ARP). TYPES
      OF STUDIES REVIEWED: The authors conducted a search for SRs on ARP on the basis
      of a set of eligibility criteria (only SRs involving ARP, with or without meta
      analyses, written in English). The authors assessed the quality of the SRs
      independently of one another by using two established checklists. RESULTS: The
      authors selected eight SRs. The results of all of the SRs indicated that ARP was
      effective in preserving the ridge volume as compared with extraction alone, but
      it did not fully prevent bone-resorptive events. None of the SRs, however,
      received the highest possible score in either of the checklists. One SR that had
      a score of 5 (of a possible 11) using one checklist and 5 (of a possible 14)
      using the other checklist had the lowest overall score. The results of this
      assessment revealed that a significant proportion of the investigators in the SRs
      did not include non-English language articles, perform hand searching of
      published literature or evaluate the gray literature. Assessment of publication
      bias and reporting of conflicts of interest also was lacking in some studies.
      Practical Implications. Although ARP appears to be an effective approach to
      preventing resorption after tooth extraction, significant structural and
      methodological variability exists among SRs on this topic. Future SRs on ARP
      should consider the use of quality assessment checklists to minimize
      methodological shortcomings for better dissemination of scientific evidence.

PMID- 24282265
TI  - Prevention and management of persistent idiopathic facial pain after dental
      implant placement.

PMID- 24282267
TI  - The impact of an oral health program on domestic violence survivors within
      community shelters.
AB  - BACKGROUND: The authors conducted a study to evaluate the impact of an oral
      health treatment program on oral health-related quality of life (OHRQoL) for
      women who were domestic violence (DV) survivors living in community shelters.
      METHODS: After completing DV education, dental residents provided treatment to
      female survivors of DV (n = 37) at on-site clinics. They administered pretest and
      posttest surveys to participants to assess their OHRQoL in terms of pain, impact
      of oral health on functioning and discomfort, embarrassment and quality of life
      overall to the participants. The authors also administered patient satisfaction
      surveys to participants to assess their satisfaction with treatment and the
      program. RESULTS: Participants reported significantly improved OHRQoL for seven
      of the eight items assessed (P < .05). They were satisfied with their treatment
      and with dental residents' performance. CONCLUSIONS: The program was effective
      and well received. Practical Implications. By participating in a one-day DV
      education program and using portable dental equipment installed in community
      shelters, dental residents and dentists can provide much needed dental treatment
      to a population of women who otherwise may not seek or have access to oral health
      care. Treatment can play an important role in DV survivors' self-esteem and
      reintegration into normal social and workplace activities.

PMID- 24282268
TI  - Sex determination from dentin and pulp in a medicolegal context.
AB  - BACKGROUND: The techniques used to determine the sex of skeletons are limited.
      The authors conducted a study to analyze the accuracy of sex identification from
      dentin and pulp via DNA isolation. METHODS: The authors extracted DNA from the
      dentin and pulp of 14 teeth by using a silica-based methodology. They used the
      amelogenin gene to determine the sex via polymerase chain reaction. beta-actin, a
      housekeeping gene, was used as a control gene. The authors checked the results in
      agarose gel and semiquantified them by using gel analysis software. RESULTS: The
      DNA yield depended on the type of tooth and was lowest in the smallest teeth
      (that is, incisors). In all cases, the authors were able to identify the sex, as
      well as the control gene, which suggests the potential to identify other genes,
      such as short tandem repeats. CONCLUSIONS: It is possible to correctly identify a
      person's sex from dentin and pulp; in instances in which one dental material is
      not available, the other material can be used with the same efficiency. Practical
      Implications. The results of this study are applicable to forensic dentistry,
      particularly in situations in which there is commingling of remains and
      fragmentary remains, and there may be only one tooth with which to identify a
      person's sex.

PMID- 24282266
TI  - Cross-sectional associations of oral health measures with cognitive function in
      late middle-aged adults: a community-based study.
AB  - BACKGROUND: It has not been established to what extent oral health is associated
      with cognitive function in late middle-aged adults. In this study, which is part
      of the national Atherosclerosis Risk in Communities (ARIC) study, the authors
      investigated whether tooth loss and periodontitis are associated with lower
      cognitive function. METHODS: The authors analyzed ARIC data measuring cognitive
      function in 11,097 participants from 1996 through 1998 according to tests of
      delayed word recall, digit-symbol substitution (DSS) and word fluency; 9,874
      participants answered dental screening questions. Of the 8,554 dentate
      participants, 5,942 received oral examinations. The authors used measures of
      dental status, number of teeth and periodontitis (classified according to the
      Biofilm-Gingival Interface Index) in multiple linear regression models to
      estimate these factors' cross-sectional association with cognitive scores,
      adjusting for sociodemographic factors, cigarette smoking, alcohol use and
      diabetes. RESULTS: Approximately 13 percent of participants were edentulous. Of
      the dentate participants, 27.3 percent had fewer than 20 teeth and 12.4 percent
      had pocket depth of 4 millimeters or more with severe bleeding. Compared with
      dentate participants, edentulous participants had lower scores for all cognitive
      tests. Among the dentate participants, having fewer teeth and gingival bleeding
      were associated with lower DSS and word fluency test scores, although periodontal
      pocket depth was not. CONCLUSIONS: In this cohort, edentulism was correlated with
      lower cognitive status. Tooth loss and gingival bleeding were markers of poorer
      executive function among dentate people. Practical Implications. The association
      of lower cognitive scores with edentulism suggests that past oral diseases may be
      a risk indicator for cognitive decline, whereas the association with gingival
      inflammation indicates a possible effect of cognitive decline on oral health.
      Practitioners should be aware that both current and historical markers of oral
      disease might be associated with decline in cognitive function, even in adults of
      late middle age.

PMID- 24282269
TI  - Use of communication techniques by Maryland dentists.
AB  - BACKGROUND: Health care providers' use of recommended communication techniques
      can increase patients' adherence to prevention and treatment regimens and improve
      patient health outcomes. The authors conducted a survey of Maryland dentists to
      determine the number and type of communication techniques they use on a routine
      basis. METHODS: The authors mailed a 30-item questionnaire to a random sample of
      1,393 general practice dentists and all 169 members of the Maryland chapter of
      the American Academy of Pediatric Dentistry. The overall response rate was 38.4
      percent. Analysis included descriptive statistics, analysis of variance and
      ordinary least squares regression analysis to examine the association of
      dentists' characteristics with the number of communication techniques used. They
      set the significance level at P < .05. RESULTS: General dentists reported
      routinely using a mean of 7.9 of the 18 communication techniques and 3.6 of the
      seven basic techniques, whereas pediatric dentists reported using a mean of 8.4
      and 3.8 of those techniques, respectively. General dentists who had taken a
      communication course outside of dental school were more likely than those who had
      not to use the 18 techniques (P < .01) but not the seven basic techniques (P <
      .05). Pediatric dentists who had taken a communication course outside of dental
      school were more likely than those who had not to use the 18 techniques (P < .05)
      and the seven basic techniques (P < .01). CONCLUSIONS: The number of
      communication techniques that dentists used routinely varied across the 18
      techniques and was low for most techniques. Practical Implications. Professional
      education is needed both in dental school curricula and continuing education
      courses to increase use of recommended communication techniques. Specifically,
      dentists and their team members should consider taking communication skills
      courses and conducting an overall evaluation of their practices for user
      friendliness.

PMID- 24282270
TI  - Dentists' leadership-related perceptions, values, experiences and behavior:
      results of a national survey.
AB  - BACKGROUND: The authors developed a survey and administered it to members of the
      American Dental Association (ADA) to elicit their views on leadership in
      dentistry, as well as to explore their leadership-related values and evaluation
      of their effectiveness as leaders, their experiences with leadership-related
      activities and perceptions of barriers to being a leader. The authors also
      examined how male and female dentists differed in their leadership-related
      responses. METHODS: The authors collected survey data from 593 ADA members (mean
      age, 51 years; standard deviation, 10.75 years). Seventy-seven percent of
      respondents were male and 85 percent were European American. RESULTS: The most
      frequently reported aspects of leadership were leadership in one's own practice
      (31 percent), in the profession (26 percent), in the community (14 percent) and
      in dental organizations (9 percent). The most valued aspects of leadership were
      being a good leader in one's own practice (mean rating = 4.64 on a five-point
      scale, with 5 = very important) and having patients perceive them as leaders
      (mean rating = 4.38). The most frequent past leadership experiences were related
      to leadership in dental organizations (47 percent), and the most frequent current
      activities were related to leadership activities in the community (40 percent).
      Time constraints (46 percent) and family obligations (20 percent) were the
      biggest barriers to taking on more of a leadership role. According to the survey
      results, female respondents valued the importance of leadership more highly than
      did male respondents. CONCLUSIONS: The results of this survey show that dentists
      perceive professional leadership as closely related to leadership in their own
      dental practices and value this type of leadership most highly. However, about 40
      percent of respondents reported that they engaged in current leadership
      activities in their communities, and 32 percent reported doing so in professional
      organizations. Practical Implications. ADA members who responded to this survey
      focused primarily on leadership in their own clinical practices. However,
      substantial numbers of dentists valued leadership activities in their communities
      and on a state and national level.

PMID- 24282271
TI  - Why are flowable resin-based composites so popular?

PMID- 24282272
TI  - A broader view of case presentation.

PMID- 24282273
TI  - Is it ethical to sign a form stating a patient received a preventive care
      examination when he actually received a different form of care?

PMID- 24282274
TI  - MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network
      adaptations that limit activity of IGF-IR inhibitors.
AB  - Although inhibition of the insulin-like growth factor (IGF) signaling pathway was
      expected to eliminate a key resistance mechanism for EGF receptor (EGFR)-driven
      cancers, the effectiveness of IGF-I receptor (IGF-IR) inhibitors in clinical
      trials has been limited. A multiplicity of survival mechanisms are available to
      cancer cells. Both IGF-IR and the ErbB3 receptor activate the PI3K/AKT/mTOR axis,
      but ErbB3 has only recently been pursued as a therapeutic target. We show that
      coactivation of the ErbB3 pathway is prevalent in a majority of cell lines
      responsive to IGF ligands and antagonizes IGF-IR-mediated growth inhibition.
      Blockade of the redundant IGF-IR and ErbB3 survival pathways and downstream
      resistance mechanisms was achieved with MM-141, a tetravalent bispecific antibody
      antagonist of IGF-IR and ErbB3. MM-141 potency was superior to monospecific and
      combination antibody therapies and was insensitive to variation in the ratio of
      IGF-IR and ErbB3 receptors. MM-141 enhanced the biologic impact of receptor
      inhibition in vivo as a monotherapy and in combination with the mTOR inhibitor
      everolimus, gemcitabine, or docetaxel, through blockade of IGF-IR and ErbB3
      signaling and prevention of PI3K/AKT/mTOR network adaptation.

PMID- 24282275
TI  - Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the
      mitotic MPS1 kinase inhibitor NMS-P715.
AB  - Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit
      structural and numerical chromosome instability (CIN). Although often implicated
      as a driver of tumor progression and drug resistance, CIN also reduces cell
      fitness and poses a vulnerability that can be exploited therapeutically. The
      spindle assembly checkpoint (SAC) ensures correct chromosome-microtubule
      attachment, thereby minimizing chromosome segregation errors. Many tumors exhibit
      upregulation of SAC components such as MPS1, which may help contain CIN within
      survivable limits. Prior studies showed that MPS1 inhibition with the small
      molecule NMS-P715 limits tumor growth in xenograft models. In cancer cell lines,
      NMS-P715 causes cell death associated with impaired SAC function and increased
      chromosome missegregation. Although normal cells appeared more resistant, effects
      on stem cells, which are the dose-limiting toxicity of most chemotherapeutics,
      were not examined. Elevated expression of 70 genes (CIN70), including MPS1,
      provides a surrogate measure of CIN and predicts poor patient survival in
      multiple tumor types. Our new findings show that the degree of CIN70 upregulation
      varies considerably among PDAC tumors, with higher CIN70 gene expression
      predictive of poor outcome. We identified a 25 gene subset (PDAC CIN25) whose
      overexpression was most strongly correlated with poor survival and included MPS1.
      In vitro, growth of human and murine PDAC cells is inhibited by NMS-P715
      treatment, whereas adipose-derived human mesenchymal stem cells are relatively
      resistant and maintain chromosome stability upon exposure to NMS-P715. These
      studies suggest that NMS-P715 could have a favorable therapeutic index and
      warrant further investigation of MPS1 inhibition as a new PDAC treatment
      strategy.

PMID- 24282276
TI  - Blocking SDF-1alpha/CXCR4 downregulates PDGF-B and inhibits bone marrow-derived
      pericyte differentiation and tumor vascular expansion in Ewing tumors.
AB  - Bone marrow cells (BMC) are critical to the expansion of the tumor vessel network
      that supports Ewing sarcoma growth. BMCs migrate to the tumor and differentiate
      into endothelial cells and pericytes. We recently demonstrated that stromal
      derived growth factor 1alpha (SDF-1alpha) regulates platelet-derived growth
      factor B (PDGF-B) and that this pathway plays a critical role in bone marrow
      derived pericyte differentiation in vitro. We investigated the role of SDF
      1alpha/PDGF-B in the tumor microenvironment in vivo in promoting bone marrow
      derived pericyte differentiation in Ewing tumors. The CXCR4 antagonist AMD 3100
      was used to disrupt the SDF-1alpha/CXCR4 axis in vivo in two xenograft Ewing
      tumor models. BMCs from GFP(+) transgenic mice were transplanted into lethally
      irradiated nude mice to track BMC migration to the tumor site. Following BMC
      engraftment, tumor-bearing mice received daily subcutaneous injections of either
      PBS or AMD 3100 for 3 weeks. Tumors were resected and tumor sections were
      analyzed by immunohistochemistry. AMD 3100 inhibited BMC differentiation into
      desmin(+) and NG2(+) pericytes, affected the morphology of the tumor vasculature,
      decreased perfusion, and increased tumor cell apoptosis. We observed smaller
      vessels with tiny lumens and a decrease in the microvessel density. AMD 3100 also
      inhibited PDGF-B protein expression in vitro and in vivo. SDF-1alpha in the tumor
      microenvironment plays a critical role in promoting pericyte formation and Ewing
      sarcoma tumor neovascularization by regulating PDGF-B expression. Interfering
      with this pathway affects tumor vascular morphology and expansion.

PMID- 24282277
TI  - GSK3 inhibitors regulate MYCN mRNA levels and reduce neuroblastoma cell viability
      through multiple mechanisms, including p53 and Wnt signaling.
AB  - Neuroblastoma is an embryonal tumor accounting for approximately 15% of childhood
      cancer deaths. There exists a clinical need to identify novel therapeutic
      targets, particularly for treatment-resistant forms of neuroblastoma. Therefore,
      we investigated the role of the neuronal master regulator GSK3 in controlling
      neuroblastoma cell fate. We identified novel GSK3-mediated regulation of MYC (c
      MYC and MYCN) mRNA levels, which may have implications for numerous MYC-driven
      cancers. In addition, we showed that certain GSK3 inhibitors induced large-scale
      cell death in neuroblastoma cells, primarily through activating apoptosis. mRNA
      seq of GSK3 inhibitor-treated cells was performed and subsequent pathway analysis
      revealed that multiple signaling pathways contributed to the loss of
      neuroblastoma cell viability. The contribution of two of the signaling pathways
      highlighted by the mRNA-seq analysis was functionally validated. Inhibition of
      the p53 tumor suppressor partly rescued the cell death phenotype, whereas
      activation of canonical Wnt signaling contributed to the loss of viability, in a
      p53-independent manner. Two GSK3 inhibitors (BIO-acetoxime and LiCl) and one
      small-molecule Wnt agonist (Wnt Agonist 1) demonstrated therapeutic potential for
      neuroblastoma treatment. These inhibitors reduced the viability of numerous
      neuroblastoma cell lines, even those derived from high-risk MYCN-amplified
      metastatic tumors, for which effective therapeutics are currently lacking.
      Furthermore, although LiCl was lethal to neuroblastoma cells, it did not reduce
      the viability of differentiated neurons. Taken together our data suggest that
      these small molecules may hold potential as effective therapeutic agents for the
      treatment of neuroblastoma and other MYC-driven cancers.

PMID- 24282278
TI  - Novel mechanism of MDA-7/IL-24 cancer-specific apoptosis through SARI induction.
AB  - Subtraction hybridization combined with induction of cancer cell terminal
      differentiation in human melanoma cells identified melanoma differentiation
      associated gene-7/interleukin-24 (mda-7/IL-24) and SARI (suppressor of AP-1,
      induced by IFN) that display potent antitumor activity. These genes are not
      constitutively expressed in cancer cells and forced expression of mda-7/IL-24
      (Ad.mda-7) or SARI (Ad.SARI) promotes cancer-specific cell death. Ectopic
      expression of mda-7/IL-24 induces SARI mRNA and protein in a panel of different
      cancer cells, leading to cell death, without harming corresponding normal cells.
      Simultaneous inhibition of K-ras downstream extracellular signal-regulated kinase
      1/2 signaling in pancreatic cancer cells reverses the translational block of MDA
      7/IL-24 and induces SARI expression and cell death. Using SARI-antisense-based
      approaches, we demonstrate that SARI expression is necessary for mda-7/IL-24
      antitumor effects. Secreted MDA-7/IL-24 protein induces antitumor "bystander"
      effects by promoting its own expression. Recombinant MDA-7/IL-24 (His-MDA-7)
      induces SARI expression, supporting the involvement of SARI in the MDA-7/IL-24
      driven autocrine loop, culminating in antitumor effects. Moreover, His-MDA-7,
      after binding to its cognate receptors (IL-20R1/IL-20R2 or IL-22R/IL-20R2),
      induces intracellular signaling by phosphorylation of p38 MAPK, leading to
      transcription of a family of growth arrest and DNA damage inducible (GADD) genes,
      culminating in apoptosis. Inhibition of p38 MAPK fails to induce SARI following
      Ad.mda-7 infection. These findings reveal the significance of the mda-7/IL-24
      SARI axis in cancer-specific killing and provide a potential strategy for
      treating both local and metastatic disease.

PMID- 24282279
TI  - Tumor suppressor NF2/Merlin is a microtubule stabilizer.
AB  - Cancer-associated mutations in oncogene products and tumor suppressors
      contributing to tumor progression manifest themselves, at least in part, by
      deregulating microtubule-dependent cellular processes that play important roles
      in many cell biological pathways, including intracellular transport, cell
      architecture, and primary cilium and mitotic spindle organization. An essential
      characteristic of microtubules in the performance of these varied cell processes
      is their ability to continuously remodel, a phenomenon known as dynamic
      instability. It is therefore conceivable that part of the normal function of
      certain cancer-causing genes is to regulate microtubule dynamic instability.
      Here, we report the results of a high-resolution live-cell image-based RNA
      interference screen targeting a collection of 70 human tumor suppressor genes to
      uncover cancer genes affecting microtubule dynamic instability. Extraction and
      computational analysis of microtubule dynamics from EB3-GFP time-lapse image
      sequences identified the products of the tumor suppressor genes NF1 and NF2 as
      potent microtubule-stabilizing proteins. Further in-depth characterization of NF2
      revealed that it binds to and stabilizes microtubules through attenuation of
      tubulin turnover by lowering both rates of microtubule polymerization and
      depolymerization as well as by reducing the frequency of microtubule
      catastrophes. The latter function appears to be mediated, in part, by inhibition
      of hydrolysis of tubulin-bound GTP on the growing microtubule plus end.

PMID- 24282280
TI  - MUC1 in macrophage: contributions to cigarette smoke-induced lung cancer.
AB  - Expression of the pro-oncogenic mucin MUC1 is elevated by inflammation in airway
      epithelial cells, but the contributions of MUC1 to the development of lung cancer
      are uncertain. In this study, we developed our finding that cigarette smoke
      increases Muc1 expression in mouse lung macrophages, where we hypothesized MUC1
      may contribute to cigarette smoke-induced transformation of bronchial epithelial
      cells. In human macrophages, cigarette smoke extract (CSE) strongly induced MUC1
      expression through a mechanism involving the nuclear receptor PPAR-gamma. CSE
      induced extracellular signal-regulated kinase (ERK) activation was also required
      for MUC1 expression, but it had little effect on MUC1 transcription. RNA
      interference-mediated attenuation of MUC1 suppressed CSE-induced secretion of TNF
      alpha from macrophages, by suppressing the activity of the TNF-alpha-converting
      enzyme (TACE), arguing that MUC1 is required for CSE-induced and TACE-mediated
      TNF-alpha secretion. Similarly, MUC1 blockade after CSE induction through
      suppression of PPAR-gamma or ERK inhibited TACE activity and TNF-alpha secretion.
      Conditioned media from CSE-treated macrophages induced MUC1 expression and
      potentiated CSE-induced transformation of human bronchial epithelial cells in a
      TNF-alpha-dependent manner. Together, our results identify a signaling pathway
      involving PPAR-gamma, ERK, and MUC1 for TNF-alpha secretion induced by CSE from
      macrophages. Furthermore, our results show how MUC1 contributes to smoking
      induced lung cancers that are driven by inflammatory signals from macrophages.

PMID- 24282281
TI  - Defective TGF-beta signaling in bone marrow-derived cells prevents hedgehog
      induced skin tumors.
AB  - Hedgehog signaling in cancer cells drives changes in the tumor microenvironment
      that are incompletely understood. Here, we report that hedgehog-driven tumors
      exhibit an increase in myeloid-derived suppressor cells (MDSC) and a decrease in
      T cells, indicative of an immunosuppressive tumor microenvironment. This change
      was associated with activated TGF-beta signaling in several cell types in basal
      cell carcinomas. We determined that TGF-beta signaling in bone marrow-derived
      cells, not keratinocytes, regulates MDSC and promotes tumor development. Tgfbr2
      deficiency in the bone marrow-derived cells also reduced the size of previously
      developed tumors in mice. We identified CCL2 as the major chemokine attracting
      MDSCs to tumor, whose expression was Tgfbr2-dependent, whereas its receptor CCR2
      was highly expressed in MDSC population. CCL2 alone was sufficient to induce
      migration of MDSCs. Moreover, the CCR2 inhibitors prevented MDSC migration toward
      skin cells in vitro, and reduced MDSC accumulation and hedgehog signaling-driven
      tumor development in mice. Our results reveal a signaling network critical for
      hedgehog signaling in cancer cells to establish an effective immunosuppressive
      microenvironment during tumor development.

PMID- 24282282
TI  - Identification of a cyclin D1 network in prostate cancer that antagonizes
      epithelial-mesenchymal restraint.
AB  - Improved clinical management of prostate cancer has been impeded by an inadequate
      understanding of molecular genetic elements governing tumor progression. Gene
      signatures have provided improved prognostic indicators of human prostate cancer.
      The TGF-beta/BMP-SMAD4 signaling pathway, which induces epithelial-mesenchymal
      transition (EMT), is known to constrain prostate cancer progression induced by
      Pten deletion. Herein, cyclin D1 inactivation reduced cellular proliferation in
      the murine prostate in vivo and in isogenic oncogene-transformed prostate cancer
      cell lines. The in vivo cyclin D1-mediated molecular signature predicted poor
      outcome of recurrence-free survival for patients with prostate cancer (K-means
      HR, 3.75, P = 0.02) and demonstrated that endogenous cyclin D1 restrains TGF
      beta, Snail, Twist, and Goosecoid signaling. Endogenous cyclin D1 enhanced Wnt
      and ES cell gene expression and expanded a prostate stem cell population. In
      chromatin immunoprecipitation sequencing, cyclin D1 occupied genes governing stem
      cell expansion and induced their transcription. The coordination of EMT
      restraining and stem cell expanding gene expression by cyclin D1 in the prostate
      may contribute to its strong prognostic value for poor outcome in biochemical
      free recurrence in human prostate cancer.

PMID- 24282283
TI  - Double-stranded DNA breaks hidden in the neutral Comet assay suggest a role of
      the sperm nuclear matrix in DNA integrity maintenance.
AB  - We used a mouse model in which sperm DNA damage was induced to understand the
      relationship of double-stranded DNA (dsDNA) breaks to sperm chromatin structure
      and to the Comet assay. Sperm chromatin fragmentation (SCF) produces dsDNA breaks
      located on the matrix attachment regions, between protamine toroids. In this
      model, epididymal sperm induced to undergo SCF can religate dsDNA breaks while
      vas deferens sperm cannot. Here, we demonstrated that the conventional neutral
      Comet assay underestimates the epididymal SCF breaks because the broken DNA ends
      remain attached to the nuclear matrix, causing the DNA to remain associated with
      the dispersion halo, and the Comet tails to be weak. Therefore, we term these
      hidden dsDNA breaks. When the Comet assay was modified to include an additional
      incubation with sodium dodecyl sulfate (SDS) and dithiothreitol (DTT) after the
      conventional lysis, thereby solubilizing the nuclear matrix, the broken DNA was
      released from the matrix, which resulted in a reduction of the sperm head halo
      and an increase in the Comet tail length, exposing the hidden dsDNA breaks.
      Conversely, SCF-induced vas deferens sperm had small halos and long tails with
      the conventional neutral Comet assay, suggesting that the broken DNA ends were
      not tethered to the nuclear matrix. These results suggest that the attachment to
      the nuclear matrix is crucial for the religation of SCF-induced DNA breaks in
      sperm. Our data suggest that the neutral Comet assay identifies only dsDNA breaks
      that are released from the nuclear matrix and that the addition of an SDS
      treatment can reveal these hidden dsDNA breaks. 

PMID- 24282284
TI  - Non-frozen preservation protocols for mature mouse oocytes dramatically extend
      their developmental competence by reducing oxidative stress.
AB  - The objective of this study was to test whether aging induces oxidative stress
      (OS) during oocyte preservation at different temperatures and whether the oocyte
      competence can be extended by antioxidant supplementation. The increase in
      activation susceptibility was efficiently prevented when oocytes were preserved
      at 37 degrees C for 9 h in HCZB medium with 10.27 mM pyruvate and 10 uM alpha
      tocopherol, at 25 degrees C for 30 h with 20.27 mM pyruvate, and at 15 degrees C
      for 96 h and at 5 degrees C for 48 h with 10.27 mM pyruvate. Satisfactory
      blastocyst development was achieved after oocyte preservation at 37 degrees C for
      9 h, at 25 degrees C for 30 h, at 15 degrees C for 48 h and at 5 degrees C for 24
      h using the above protocols but with cysteamine/cystine supplementation. Transfer
      of blastocysts obtained from the above protocols showed no difference in
      pregnancy outcome between newly ovulated and preserved oocytes. Because oocytes
      preserved at 15 degrees C for 48 h were fertilized after a 6-h recovery culture,
      aging of ovulated mouse oocytes has been successfully prevented for 54 h. Assays
      for ROS and glutathione indicated that in vitro preservation caused marked OS in
      oocytes. In conclusion, marked OS was observed following in vitro preservation of
      mature oocytes at different temperatures. Whereas any protocol that reduced OS
      could inhibit activation susceptibility, only those protocols that decreased OS
      while increasing glutathione synthesis could sustain oocyte competence. 

PMID- 24282285
TI  - Digital dome.

PMID- 24282287
TI  - LGR5 positivity defines stem-like cells in colorectal cancer.
AB  - Like normal colorectal epithelium, colorectal carcinomas (CRCs) are organized
      hierarchically and include populations of cells with stem-like properties.
      Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) is associated
      with these stem cells in normal colorectal epithelium; however, the precise
      function of LGR5 in CRC remains largely unknown. Here, we analyzed the functional
      and molecular consequences of short hairpin RNA-mediated silencing of LGR5 in CRC
      cell lines SW480 and HT-29. Additionally, we exposed Lgr5-EGFP-IRES-CreERT2 mice
      to azoxymethane/dextrane sodium sulfate (AOM/DSS), which induces inflammation
      driven colon tumors. Tumors were then flow-sorted into fractions of epithelial
      cells that expressed high or low levels of Lgr5 and were molecularly
      characterized using gene expression profiling and array comparative genomic
      hybridization. Silencing of LGR5 in SW480 CRC cells resulted in a depletion of
      spheres but did not affect adherently growing cells. Spheres expressed higher
      levels of several stem cell-associated genes than adherent cells, including LGR5.
      Silencing of LGR5 reduced proliferation, migration and colony formation in vitro
      and tumorigenicity in vivo. In accordance with these results, NOTCH signaling was
      downregulated upon LGR5 silencing. In AOM/DSS-induced colon tumors, Lgr5 high
      cells showed higher levels of several stem cell-associated genes and higher Wnt
      signaling than Lgr5 low tumor cells and Lgr5 high normal colon cells. Array
      comparative genomic hybridization revealed no genomic imbalances in either tumor
      cell fraction. Our data elucidate mechanisms that define the role of LGR5 as a
      marker for stem-like cells in CRC. 

PMID- 24282288
TI  - Secretory leukocyte protease inhibitor modulates urethane-induced lung
      carcinogenesis.
AB  - Secretory leukocyte protease inhibitor (SLPI), 11.7 kDa serine protease
      inhibitor, is produced primarily in the respiratory tract, but it is often
      elevated in lung, head/neck and ovarian cancers. SLPI expression in relation to
      cancer progression, metastasis and invasion has been studied extensively in non
      small cell lung cancer. However, the role of SLPI during the early stages of
      carcinogenesis remains unknown. We hypothesized that SLPI is required from the
      initiation and promotion to the progression of lung carcinogenesis. A skin
      allograft model using SLPI-knockout (SLPI-KO) mice and short hairpin RNA-treated
      cells was used to demonstrate that SLPI expression in tumor cells is crucial for
      tumor formation. Moreover, lung tumorigenesis induced by urethane, a chemical
      lung carcinogen, was significantly suppressed in SLPI-KO mice in association with
      decreased nuclear factor-kappaB (NF-kappaB) activity. SLPI deficiency also
      resulted in decreased cell numbers and decreased production of inflammatory
      cytokines in bronchoalveolar lavage fluids. The suppression of NF-kappaB
      activation in SLPI-KO mice was associated with lower expression of NF-kappaB
      related survival genes and DNA repair genes. Our findings demonstrate that SLPI
      plays an important role from the initial stages of lung carcinogenesis to the
      progression of lung cancer in an NF-kappaB-dependent manner. 

PMID- 24282289
TI  - Anti-YKL-40 antibody and ionizing irradiation synergistically inhibit tumor
      vascularization and malignancy in glioblastoma.
AB  - Chemo/radiotherapies are the most common adjuvant modality treated for patients
      with glioblastoma (GBM) following surgery. However, the overall therapeutic
      benefits are still uncertain, as the mortality remains high. Elevated expression
      of YKL-40 in GBM was correlated with increases in mural cell-associated vessel
      coverage, stability and density, and decreases in vessel permeability and disease
      survival. To explore the potential role of YKL-40 in mural cell-mediated tumor
      vascularization, we employed an anti-YKL-40 neutralizing antibody (mAY) and
      ionizing irradiation (IR) in xenografted brain tumor models. Although single
      treatment with mAY or IR partially increased mouse survival, their combination
      led to dramatic inhibition in tumor growth and increases in mouse survival. mAY
      blocked mural cell-mediated vascular stability, integrity and angiogenesis;
      whereas IR merely promoted tumor cell and vascular cell apoptosis. Vascular
      radioresistance is at least partially attributed to expression of YKL-40 in mural
      cells. These divergent effects were also recapitulated in cultured systems using
      endothelial cells and mural cells differentiated from glioblastoma stem-like
      cells (GSCs). Dysfunction of intercellular contact N-cadherin was found to
      mediate mAY-inhibited vascularization. Collectively, the data suggest that the
      conjunction therapy with mAY and IR synergistically inhibit tumor vascularization
      and progression. The evidence may shed light on a new adjuvant therapy in clinic.

PMID- 24282290
TI  - [6]-shogaol inhibits growth and induces apoptosis of non-small cell lung cancer
      cells by directly regulating Akt1/2.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality
      worldwide. Despite progress in developing chemotherapeutics for the treatment of
      NSCLC, primary and secondary resistance limits therapeutic success. NSCLC cells
      exhibit multiple mutations in the epidermal growth factor receptor (EGFR), which
      cause aberrant activation of diverse cell signaling pathways. Therefore,
      suppression of the inappropriate amplification of EGFR downstream signaling
      cascades is considered to be a rational therapeutic and preventive strategy for
      the management of NSCLC. Our initial molecular target-oriented virtual screening
      revealed that the ginger components, including [6]-shogaol, [6]-paradol and [6]
      gingerol, seem to be potential candidates for the prevention and treatment of
      NSCLC. Among the compounds, [6]-shogaol showed the greatest inhibitory effects on
      the NSCLC cell proliferation and anchorage-independent growth. [6]-Shogaol
      induced cell cycle arrest (G1 or G2/M) and apoptosis. Furthermore, [6]-shogaol
      inhibited Akt kinase activity, a downstream mediator of EGFR signaling, by
      binding with an allosteric site of Akt. In NCI-H1650 lung cancer cells, [6]
      shogaol reduced the constitutive phosphorylation of signal transducer and
      activator of transcription-3 (STAT3) and decreased the expression of cyclin D1/3,
      which are target proteins in the Akt signaling pathway. The induction of
      apoptosis in NCI-H1650 cells by [6]-shogaol corresponded with the cleavage of
      caspase-3 and caspase-7. Moreover, intraperitoneal administration of [6]-shogaol
      inhibited the growth of NCI-H1650 cells as tumor xenografts in nude mice. [6]
      Shogaol suppressed the expression of Ki-67, cyclin D1 and phosphorylated Akt and
      STAT3 and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling-positivity in xenograft tumors. The current study clearly indicates that
      [6]-shogaol can be exploited for the prevention and/or treatment of NSCLC.

PMID- 24282291
TI  - Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the
      repolarization process of atrial myocytes.
AB  - AIMS: Small conductance Ca(2+)-activated K(+) channels (K(Ca)2 or SK channels)
      have been reported in excitable cells, where they aid in integrating changes in
      intracellular Ca(2+) (Ca(i)2+) with membrane potentials. We have recently
      reported the functional expression of SK channels in human and mouse cardiac
      myocytes. Additionally, we have found that the channel is highly expressed in
      atria compared with the ventricular myocytes. We demonstrated that human cardiac
      myocytes expressed all three members of SK channels (SK1, 2, and 3); moreover,
      the different members are capable of forming heteromultimers. Here, we directly
      tested the contribution of SK3 to the overall repolarization of atrial action
      potentials. METHODS AND RESULTS: We took advantage of a mouse model with site
      specific insertion of a tetracycline-based genetic switch in the 5' untranslated
      region of the KCNN3 (SK3 channel) gene (SK3(T/T)). The gene-targeted animals
      overexpress the SK3 channel without interfering with the normal profile of SK3
      expression. Whole-cell, patch-clamp techniques show a significant shortening of
      the action potential duration mainly at 90% repolarization (APD90) in atrial
      myocytes from the homozygous SK3(T/T) animals. Conversely, treatment with dietary
      doxycycline results in a significant prolongation of APD90 in atrial myocytes
      from SK3(T/T) animals. We further demonstrate that the shortening of APDs in SK3
      overexpression mice predisposes the animals to inducible atrial arrhythmias.
      CONCLUSION: SK3 channel contributes importantly towards atrial action potential
      repolarization. Our data suggest the important role of the SK3 isoform in atrial
      myocytes.

PMID- 24282292
TI  - Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of
      huntingtin as modulators of polyglutamine aggregation.
AB  - Huntington disease is caused by mutational expansion of the CAG trinucleotide
      within exon 1 of the huntingtin (Htt) gene. Exon 1 spanning N-terminal fragments
      (NTFs) of the Htt protein result from aberrant splicing of transcripts of mutant
      Htt. NTFs typically encompass a polyglutamine tract flanked by an N-terminal 17
      residue amphipathic stretch (N17) and a C-terminal 38-residue proline-rich
      stretch (C38). We present results from in vitro biophysical studies that quantify
      the driving forces for and mechanisms of polyglutamine aggregation as modulated
      by N17 and C38. Although N17 is highly soluble by itself, it lowers the
      saturation concentration of soluble NTFs and increases the driving force, vis-a
      vis homopolymeric polyglutamine, for forming insoluble aggregates. Kinetically,
      N17 accelerates fibril formation and destabilizes nonfibrillar intermediates. C38
      is also highly soluble by itself, and it lends its high intrinsic solubility to
      lower the driving force for forming insoluble aggregates by increasing the
      saturation concentration of soluble NTFs. In NTFs with both modules, N17 and C38
      act synergistically to destabilize nonfibrillar intermediates (N17 effect) and
      lower the driving force for forming insoluble aggregates (C38 effect).
      Morphological studies show that N17 and C38 promote the formation of ordered
      fibrils by NTFs. Homopolymeric polyglutamine forms a mixture of amorphous
      aggregates and fibrils, and its aggregation mechanisms involve early formation of
      heterogeneous distributions of nonfibrillar species. We propose that N17 and C38
      act as gatekeepers that control the intrinsic heterogeneities of polyglutamine
      aggregation. This provides a biophysical explanation for the modulation of in
      vivo NTF toxicities by N17 and C38. 

PMID- 24282293
TI  - Collective polarization model for gradient sensing via Dachsous-Fat intercellular
      signaling.
AB  - Dachsous-Fat signaling via the Hippo pathway influences proliferation during
      Drosophila development, and some of its mammalian homologs are tumor suppressors,
      highlighting its role as a universal growth regulator. The Fat/Hippo pathway
      responds to morphogen gradients and influences the in-plane polarization of cells
      and orientation of divisions, linking growth with tissue patterning. Remarkably,
      the Fat pathway transduces a growth signal through the polarization of
      transmembrane complexes that responds to both morphogen level and gradient.
      Dissection of these complex phenotypes requires a quantitative model that
      provides a systematic characterization of the pathway. In the absence of detailed
      knowledge of molecular interactions, we take a phenomenological approach that
      considers a broad class of simple models, which are sufficiently constrained by
      observations to enable insight into possible mechanisms. We predict two modes of
      local/cooperative interactions among Fat-Dachsous complexes, which are necessary
      for the collective polarization of tissues and enhanced sensitivity to weak
      gradients. Collective polarization convolves level and gradient of input signals,
      reproducing known phenotypes while generating falsifiable predictions. Our
      construction of a simplified signal transduction map allows a generalization of
      the positional value model and emphasizes the important role intercellular
      interactions play in growth and patterning of tissues. 

PMID- 24282294
TI  - Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like
      disease in the Fas(lpr) mouse.
AB  - MicroRNA-155 (miR-155) regulates antibody responses and subsequent B-cell
      effector functions to exogenous antigens. However, the role of miR-155 in
      systemic autoimmunity is not known. Using the death receptor deficient (Fas(lpr))
      lupus-prone mouse, we show here that ablation of miR-155 reduced autoantibody
      responses accompanied by a decrease in serum IgG but not IgM anti-dsDNA
      antibodies and a reduction of kidney inflammation. MiR-155 deletion in Fas(lpr) B
      cells restored the reduced SH2 domain-containing inositol 5'-phosphatase 1 to
      normal levels. In addition, coaggregation of the Fc gamma receptor IIB with the B
      cell receptor in miR-155(-/-)-Fas(lpr) B cells resulted in decreased ERK
      activation, proliferation, and production of switched antibodies compared with
      miR-155 sufficient Fas(lpr) B cells. Thus, by controlling the levels of SH2
      domain-containing inositol 5'-phosphatase 1, miR-155 in part maintains an
      activation threshold that allows B cells to respond to antigens. 

PMID- 24282295
TI  - Prostate cancer originating in basal cells progresses to adenocarcinoma
      propagated by luminal-like cells.
AB  - The relationship between the cells that initiate cancer and the cancer stem-like
      cells that propagate tumors has been poorly defined. In a human prostate tissue
      transformation model, basal cells expressing the oncogenes Myc and myristoylated
      AKT can initiate heterogeneous tumors. Tumors contain features of acinar-type
      adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell
      carcinoma marked by activated beta-catenin. Lentiviral integration site analysis
      revealed that alternative histological phenotypes can be clonally derived from a
      common cell of origin. In advanced disease, adenocarcinoma can be propagated by
      self-renewing tumor cells with an androgen receptor-low immature luminal
      phenotype in the absence of basal-like cells. These data indicate that advanced
      prostate adenocarcinoma initiated in basal cells can be maintained by luminal
      like tumor-propagating cells. Determining the cells that maintain human prostate
      adenocarcinoma and the signaling pathways characterizing these tumor-propagating
      cells is critical for developing effective therapeutic strategies against this
      population. 

PMID- 24282296
TI  - Intestinal HIF2alpha promotes tissue-iron accumulation in disorders of iron
      overload with anemia.
AB  - Several distinct congenital disorders can lead to tissue-iron overload with
      anemia. Repeated blood transfusions are one of the major causes of iron overload
      in several of these disorders, including beta-thalassemia major, which is
      characterized by a defective beta-globin gene. In this state, hyperabsorption of
      iron is also observed and can significantly contribute to iron overload. In beta
      thalassemia intermedia, which does not require blood transfusion for survival,
      hyperabsorption of iron is the leading cause of iron overload. The mechanism of
      increased iron absorption in beta-thalassemia is unclear. We definitively
      demonstrate, using genetic mouse models, that intestinal hypoxia-inducible factor
      2alpha (HIF2alpha) and divalent metal transporter-1 (DMT1) are activated early in
      the pathogenesis of beta-thalassemia and are essential for excess iron
      accumulation in mouse models of beta-thalassemia. Moreover, thalassemic mice with
      established iron overload had significant improvement in tissue-iron levels and
      anemia following disruption of intestinal HIF2alpha. In addition to repeated
      blood transfusions and increased iron absorption, chronic hemolysis is the major
      cause of tissue-iron accumulation in anemic iron-overload disorders caused by
      hemolytic anemia. Mechanistic studies in a hemolytic anemia mouse model
      demonstrated that loss of intestinal HIF2alpha/DMT1 signaling led to decreased
      tissue-iron accumulation in the liver without worsening the anemia. These data
      demonstrate that dysregulation of intestinal hypoxia and HIF2alpha signaling is
      critical for progressive iron overload in beta-thalassemia and may be a novel
      therapeutic target in several anemic iron-overload disorders. 

PMID- 24282297
TI  - Tuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development
      of dendritic cells.
AB  - Coordination of cell metabolism and immune signals is crucial for lymphocyte
      priming. Emerging evidence also highlights the importance of cell metabolism for
      the activation of innate immunity upon pathogen challenge, but there is little
      evidence of how this process contributes to immune cell development. Here we show
      that differentiation of dendritic cells (DCs) from bone marrow precursors is
      associated with dynamic regulation of mechanistic target of rapamycin (mTOR)
      complex 1 (mTORC1) signaling and cell metabolism. Unexpectedly, enhancing mTORC1
      activity via ablation of its negative regulator tuberous sclerosis 1 (Tsc1)
      impaired DC development in vivo and in vitro, associated with defective cell
      survival and proliferation. Moreover, Tsc1 deficiency caused DC spontaneous
      maturation but a propensity to differentiate into other lineages, and attenuated
      DC-mediated effector TH1 responses. Mechanistically, Tsc1-deficient DCs exhibited
      increased glycolysis, mitochondrial respiration, and lipid synthesis that were
      partly mediated by the transcription factor Myc, highlighting a key role of Tsc1
      in modulating metabolic programming of DC differentiation. Further, Tsc1 signaled
      through Rheb to down-regulate mTORC1 for proper DC development, whereas its
      effect at modulating mTOR complex 2 (mTORC2) activity was largely dispensable.
      Our results demonstrate that the interplay between Tsc1-Rheb-mTORC1 signaling and
      Myc-dependent bioenergetic and biosynthetic activities constitutes a key
      metabolic checkpoint to orchestrate DC development. 

PMID- 24282299
TI  - Human resistin, a proinflammatory cytokine, shows chaperone-like activity.
AB  - Resistin, a cysteine-rich adipocytokine, proposed as a link between obesity and
      diabetes in mice, was shown as a proinflammatory molecule in humans. We earlier
      reported that human resistin (hRes), a trimer, was resistant to heat and urea
      denaturation, existed in an oligomeric polydispersed state, and showed a
      concentration-dependent conformational change. These properties and an intimate
      correlation of hRes expression with cellular stress prompted us to investigate
      hRes as a possible chaperone. Here, we show that recombinant human resistin was
      able to protect the heat-labile enzymes citrate synthase and Nde1 from thermal
      aggregation and inactivation and was able to refold and restore their enzymatic
      activities after heat/guanidinium chloride denaturation. Furthermore, recombinant
      human resistin could bind misfolded proteins only. Molecular dynamics-based
      association-dissociation kinetics of hRes subunits pointed to resistin being a
      molecular chaperone. Bis-ANS, which blocks surface hydrophobicity, abrogated the
      chaperone activity of hRes, establishing the importance of surface hydrophobicity
      for chaperone activity. Replacement of Phe49 with Tyr (F49YhRes), a critical
      residue within the hydrophobic patch of hRes, although it could prevent thermal
      aggregation of citrate synthase and Nde1, was unable to refold and restore their
      activities. Treatment of U937 cells with tunicamycin/thapsigargin resulted in
      reduced hRes secretion and concomitant localization in the endoplasmic reticulum.
      Escherichia coli transformants expressing hRes could be rescued from thermal
      stress, pointing to hRes's chaperone-like function in vivo. HeLa cells
      transfected with hRes showed protection from thapsigargin-induced apoptosis. In
      conclusion, hRes, an inflammatory protein, additionally exhibited chaperone-like
      properties, suggesting a possible link between inflammation and cellular stress. 

PMID- 24282298
TI  - Nfatc1 orchestrates aging in hair follicle stem cells.
AB  - Hair production is fueled by stem cells (SCs), which transition between cyclical
      bouts of rest and activity. Here, we explore why hair growth wanes with age. We
      show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and
      abbreviated growth phases and are delayed in response to tissue-regenerating
      cues. Aged HFSCs are poor at initiating proliferation and show diminished self
      renewing capacity upon extensive use. Only modestly restored by parabiosis, these
      features are rooted in elevated cell-intrinsic sensitivity and local elevation in
      bone morphogenic protein (BMP) signaling. Transcriptional profiling presents
      differences consistent with defects in aged HFSC activation. Notably, BMP
      /calcium-regulated, nuclear factor of activated T-cell c1 (NFATc1) in HFSCs
      becomes recalcitrant to its normal down-regulating cues, and NFATc1 ChIP
      sequencing analyses reveal a marked enrichment of NFATc1 target genes within the
      age-related signature. Moreover, aged HFSCs display more youthful levels of hair
      regeneration when BMP and/or NFATc1 are inhibited. These results provide unique
      insights into how skin SCs age. 

PMID- 24282300
TI  - Nucleosomes and centromeric DNA packaging.

PMID- 24282301
TI  - Quantitative exploration of the molecular origin of the activation of GTPase.
AB  - GTPases play a major role in cellular processes, and gaining quantitative
      understanding of their activation demands reliable free energy surfaces of the
      relevant mechanistic paths in solution, as well as the interpolation of this
      information to GTPases. Recently, we generated ab initio quantum
      mechanical/molecular mechanical free energy surfaces for the hydrolysis of
      phosphate monoesters in solution, establishing quantitatively that the barrier
      for the reactions with a proton transfer (PT) step from a single attacking water
      (1 W) is higher than the one where the PT is assisted by a second water (2 W).
      The implication of this finding on the activation of GTPases is quantified here,
      by using the ab initio solution surfaces to calibrate empirical valence bond
      surfaces and then exploring the origin of the activation effect. It is found
      that, although the 2 W PT path is a new element, this step is not rate
      determining, and the catalytic effect is actually due to the electrostatic
      stabilization of the pre-PT transition state and the subsequent plateau. Thus,
      the electrostatic catalytic effect found in our previous studies of the Ras
      GTPase activating protein (RasGAP) and the elongation factor-Tu (EF-Tu) with a 1
      W mechanism is still valid for the 2 W path. Furthermore, as found before, the
      corresponding activation appears to involve a major allosteric effect. Overall,
      we believe that our finding is general to both GTPases and ATPases. In addition
      to the biologically relevant finding, we also provide a critical discussion of
      the requirements from reliable surfaces for enzymatic reactions.

PMID- 24282302
TI  - Immunoglobulin knockout chickens via efficient homologous recombination in
      primordial germ cells.
AB  - Gene targeting by homologous recombination or by sequence-specific nucleases
      allows the precise modification of genomes and genes to elucidate their
      functions. Although gene targeting has been used extensively to modify the
      genomes of mammals, fish, and amphibians, a targeting technology has not been
      available for the avian genome. Many of the principles of humoral immunity were
      discovered in chickens, yet the lack of gene targeting technologies in birds has
      limited biomedical research using this species. Here we describe targeting the
      joining (J) gene segment of the chicken Ig heavy chain gene by homologous
      recombination in primordial germ cells to establish fully transgenic chickens
      carrying the knockout. In homozygous knockouts, Ig heavy chain production is
      eliminated, and no antibody response is elicited on immunization. Migration of B
      lineage precursors into the bursa of Fabricius is unaffected, whereas development
      into mature B cells and migration from the bursa are blocked in the mutants.
      Other cell types in the immune system appear normal. Chickens lacking the
      peripheral B-cell population will provide a unique experimental model to study
      avian immune responses to infectious disease. More generally, gene targeting in
      avian primordial germ cells will foster advances in diverse fields of biomedical
      research such as virology, stem cells, and developmental biology, and provide
      unique approaches in biotechnology, particularly in the field of antibody
      discovery. 

PMID- 24282303
TI  - Sleep spindles are generated in the absence of T-type calcium channel-mediated
      low-threshold burst firing of thalamocortical neurons.
AB  - T-type Ca(2+) channels in thalamocortical (TC) neurons have long been considered
      to play a critical role in the genesis of sleep spindles, one of several TC
      oscillations. A classical model for TC oscillations states that reciprocal
      interaction between synaptically connected GABAergic thalamic reticular nucleus
      (TRN) neurons and glutamatergic TC neurons generates oscillations through T-type
      channel-mediated low-threshold burst firings of neurons in the two nuclei. These
      oscillations are then transmitted from TC neurons to cortical neurons,
      contributing to the network of TC oscillations. Unexpectedly, however, we found
      that both WT and KO mice for CaV3.1, the gene for T-type Ca(2+) channels in TC
      neurons, exhibit typical waxing-and-waning sleep spindle waves at a similar
      occurrence and with similar amplitudes and episode durations during non-rapid eye
      movement sleep. Single-unit recording in parallel with electroencephalography in
      vivo confirmed a complete lack of burst firing in the mutant TC neurons. Of
      particular interest, the tonic spike frequency in TC neurons was significantly
      increased during spindle periods compared with nonspindle periods in both
      genotypes. In contrast, no significant change in burst firing frequency between
      spindle and nonspindle periods was noted in the WT mice. Furthermore, spindle
      like oscillations were readily generated within intrathalamic circuits composed
      solely of TRN and TC neurons in vitro in both the KO mutant and WT mice. Our
      findings call into question the essential role of low-threshold burst firings in
      TC neurons and suggest that tonic firing is important for the generation and
      propagation of spindle oscillations in the TC circuit. 

PMID- 24282304
TI  - Cross-over of RNA 3'-phosphate ligase into the DNA world.

PMID- 24282305
TI  - Rubella virus capsid protein structure and its role in virus assembly and
      infection.
AB  - Rubella virus (RV) is a leading cause of birth defects due to infectious agents.
      When contracted during pregnancy, RV infection leads to severe damage in fetuses.
      Despite its medical importance, compared with the related alphaviruses, very
      little is known about the structure of RV. The RV capsid protein is an essential
      structural component of virions as well as a key factor in virus-host
      interactions. Here we describe three crystal structures of the structural domain
      of the RV capsid protein. The polypeptide fold of the RV capsid protomer has not
      been observed previously. Combining the atomic structure of the RV capsid protein
      with the cryoelectron tomograms of RV particles established a low-resolution
      structure of the virion. Mutational studies based on this structure confirmed the
      role of amino acid residues in the capsid that function in the assembly of
      infectious virions. 

PMID- 24282306
TI  - Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell
      proliferation.
AB  - The association between lymphopenia and autoimmunity is recognized, but the
      underlying mechanisms are poorly understood and have not been studied
      systematically in humans. People with multiple sclerosis treated with the
      lymphocyte-depleting monoclonal antibody alemtuzumab offer a unique opportunity
      to study this phenomenon; one in three people develops clinical autoimmunity, and
      one in three people develops asymptomatic autoantibodies after treatment. Here,
      we show that T-cell recovery after alemtuzumab is driven by homeostatic
      proliferation, leading to the generation of chronically activated (CD28(
      )CD57(+)), highly proliferative (Ki67(+)), oligoclonal, memory-like CD4 and CD8 T
      cells (CCR7(-)CD45RA(-) or CCR7(-)CD45RA(+)) capable of producing proinflammatory
      cytokines. Individuals who develop autoimmunity after treatment are no more
      lymphopenic than their nonautoimmune counterparts, but they show reduced
      thymopoiesis and generate a more restricted T-cell repertoire. Taken together,
      these findings demonstrate that homeostatic proliferation drives lymphopenia
      associated autoimmunity in humans. 

PMID- 24282307
TI  - Characterization of the human ESC transcriptome by hybrid sequencing.
AB  - Although transcriptional and posttranscriptional events are detected in RNA-Seq
      data from second-generation sequencing, full-length mRNA isoforms are not
      captured. On the other hand, third-generation sequencing, which yields much
      longer reads, has current limitations of lower raw accuracy and throughput. Here,
      we combine second-generation sequencing and third-generation sequencing with a
      custom-designed method for isoform identification and quantification to generate
      a high-confidence isoform dataset for human embryonic stem cells (hESCs). We
      report 8,084 RefSeq-annotated isoforms detected as full-length and an additional
      5,459 isoforms predicted through statistical inference. Over one-third of these
      are novel isoforms, including 273 RNAs from gene loci that have not previously
      been identified. Further characterization of the novel loci indicates that a
      subset is expressed in pluripotent cells but not in diverse fetal and adult
      tissues; moreover, their reduced expression perturbs the network of pluripotency
      associated genes. Results suggest that gene identification, even in well
      characterized human cell lines and tissues, is likely far from complete. 

PMID- 24282308
TI  - Toll-like receptor 9 and 21 have different ligand recognition profiles and
      cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish.
AB  - CpG-oligodeoxynucleotides (CpG-ODNs) are potent immune stimuli currently under
      investigation as antimicrobial agents for different species. Toll-like receptor
      (TLR) 9 and TLR21 are the cellular receptors of CpG-ODN in mammals and chickens,
      respectively. The avian genomes lack TLR9, whereas mammalian genomes lack TLR21.
      Although fish contain both of these genes, the biological functions of fish TLR9
      and TLR21 have not been investigated previously. In this study, we comparatively
      investigated zebrafish TLR9 (zebTLR9) and TLR21 (zebTLR21). The two TLRs have
      similar expression profiles in zebrafish. They are expressed during early
      development stages and are preferentially expressed in innate immune function
      related organs in adult fish. Results from cell-based activation assays indicate
      that these two zebrafish TLRs are functional, responding to CpG-ODN but not to
      other TLR ligands. zebTLR9 broadly recognized CpG-ODN with different CpG motifs,
      but CpG-ODN with GACGTT or AACGTT had better activity to this TLR. In contrast,
      zebTLR21 responded preferentially to CpG-ODN with GTCGTT motifs. The distinctive
      ligand recognition profiles of these two TLRs were determined by their
      ectodomains. Activation of these two TLRs by CpG-ODN occurred inside the cells
      and was modulated by UNC93B1. The biological functions of these two TLRs were
      further investigated. The CpG-ODNs that activate both zebTLR9 and zebTLR21 were
      more potent than others that activate only zebTLR9 in the activation of cytokine
      productions and were more bactericidal in zebrafish. These results suggest that
      zebTLR9 and zebTLR21 cooperatively mediate the antimicrobial activities of CpG
      ODN. Overall, this study provides a molecular basis for the activities of CpG-ODN
      in fish. 

PMID- 24282310
TI  - Using 'nudge' principles for order set design: a before and after evaluation of
      an electronic prescribing template in critical care.
AB  - OBJECTIVE: Computerised order sets have the potential to reduce clinical
      variation and improve patient safety but the effect is variable. We sought to
      evaluate the impact of changes to the design of an order set on the delivery of
      chlorhexidine mouthwash and hydroxyethyl starch (HES) to patients in the
      intensive care unit. METHODS: The study was conducted at University Hospitals
      Bristol NHS Foundation Trust, UK. Our intensive care unit uses a clinical
      information system (CIS). All drugs and fluids are prescribed with the CIS and
      drug and fluid charts are stored within a database. Chlorhexidine mouthwash was
      added as a default prescription to the prescribing template in January 2010. HES
      was removed from the prescribing template in April 2009. Both interventions were
      available to prescribe manually throughout the study period. We conducted a
      database review of all patients eligible for each intervention before and after
      changes to the configuration of choices within the prescribing system. RESULTS:
      2231 ventilated patients were identified as appropriate for treatment with
      chlorhexidine, 591 before the intervention and 1640 after. 55.3% were prescribed
      chlorhexidine before the change and 90.4% after (p<0.001). 6199 patients were
      considered in the HES intervention, 2177 before the intervention and 4022 after.
      The mean volume of HES infused per patient fell from 630 mL to 20 mL after the
      change (p<0.001) and the percentage of patients receiving HES fell from 54.1% to
      3.1% (p<0.001). These results were well sustained with time. CONCLUSIONS: The
      presentation of choices within an electronic prescribing system influenced the
      delivery of evidence-based interventions in a predictable way and the effect was
      well sustained. This approach has the potential to enhance the effectiveness of
      computerised order sets.

PMID- 24282309
TI  - Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin
      like specificity and couples receptor activation.
AB  - Drosophila Toll functions in embryonic development and innate immunity and is
      activated by an endogenous ligand, Spatzle (Spz). The related Toll-like receptors
      in vertebrates also function in immunity but are activated directly by pathogen
      associated molecules such as bacterial endotoxin. Here, we present the crystal
      structure at 2.35-A resolution of dimeric Spz bound to a Toll ectodomain
      encompassing the first 13 leucine-rich repeats. The cystine knot of Spz binds the
      concave face of the Toll leucine-rich repeat solenoid in an area delineated by N
      linked glycans and induces a conformational change. Mutagenesis studies confirm
      that the interface observed in the crystal structure is relevant for signaling.
      The asymmetric binding mode of Spz to Toll is similar to that of nerve growth
      factor (NGF) in complex with the p75 neurotrophin receptor but is distinct from
      that of microbial ligands bound to the Toll-like receptors. Overall, this study
      indicates an allosteric signaling mechanism for Toll in which ligand binding to
      the N terminus induces a conformational change that couples to homodimerization
      of juxtamembrane structures in the Toll ectodomain C terminus. 

PMID- 24282312
TI  - Recurrent cardiac chloroma presenting as acute chest pain.

PMID- 24282313
TI  - Nail gun attempted suicide and traumatic ventricular perforations.

PMID- 24282314
TI  - Phthalate-induced pathology in the foetal testis involves more than decreased
      testosterone production.
AB  - Foetal exposure to phthalates is known to adversely impact male reproductive
      development and function. Developmental anomalies of reproductive tract have been
      attributed to impaired testosterone synthesis. However, species differences in
      the ability to produce testosterone have been noted; e.g., following foetal
      exposure, abnormal clustering of Leydig cells or decreased production of
      testosterone that is manifested in rats does not occur in mice or humans.
      Nonetheless, other facets of testicular dysgenesis occur in both rats and mice as
      well as in some other species tested. We recently published a comprehensive
      evaluation of the foetal rat testis proteome, following in utero exposure to
      diethylhexyl phthalate (DEHP), which revealed changes in individual proteins that
      are known to be factors in cellular differentiation and migration or related to
      the capacity of the foetal Leydig cell to produce testosterone and fit a pathway
      network in which each is regulated directly or indirectly by oestradiol. Plasma
      oestradiol indeed was found to be elevated approximately twofold in 19-day-old
      DEHP-exposed foetal male rats. In this brief review, we discuss our new findings
      vis-a-vis 'oestrogen hypothesis' as a cause for testicular dysgenesis syndrome. 

PMID- 24282315
TI  - Current exposure of 200 pregnant Danish women to phthalates, parabens and
      phenols.
AB  - Many phthalates, parabens and phenols are suspected to have endocrine-disrupting
      properties in humans. They are found in consumer products, including food
      wrapping, cosmetics and building materials. The foetus is particularly vulnerable
      and exposure to these chemicals therefore is of concern for pregnant women. We
      investigated current exposure to several commonly used phthalates, parabens and
      phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were
      collected between 8 and 30 weeks of gestation and analysed for metabolites of ten
      phenols, seven parabens and 16 phthalate by liquid chromatography-tandem mass
      spectrometry representing 26 non-persistent compounds. The majority of analytes
      were present in the urine sample collected from most women who participated.
      Thus, in 174 of the 200 women, metabolites of more than 13 (>50%) of 26 compounds
      were detected simultaneously. The number of compounds detected per woman (either
      as the parent compound or its metabolite(s)) ranged from 7 to 21 with a median of
      16. The majority of compounds correlated positively with each other within and
      between chemical groups, suggesting combined exposure sources. Estimated daily
      intakes (DIs) of phthalates and bisphenol A (BPA) were below their individual
      tolerable DI (TDI) and with hazard quotients below 1. In conclusion, we found
      detectable levels of phthalate metabolites, parabens and phenols in almost all
      pregnant women, suggesting combined multiple exposures. Although the estimated DI
      of phthalates and BPA for an individual was below TDI, our results still raise
      concern, as current toxicological risk assessments in humans do not take into
      account simultaneous exposure. The true cumulative risk for the foetus may
      therefore be underestimated. 

PMID- 24282316
TI  - Low physical activity is a determinant for elevated blood pressure in high
      cardiovascular risk obstructive sleep apnea.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) is associated with cardiovascular
      morbidity, including hypertension. Beyond the severity of nocturnal hypoxia,
      other factors such as metabolic abnormalities but also sedentary behaviors and
      insufficient physical activity may contribute to elevated blood pressure (BP). To
      clarify the respective role of these factors as determinants of BP in OSA
      patients, we examined the relationship between BP and anthropometrics, severity
      of sleep apnea, and objectively measured physical activity and sedentary
      behaviors. METHODS: Ninety-five adults presenting with OSA (apnea-hypopnea index
      > 10 events/h) and high cardiovascular risk (63.3 +/- 8.8 y; body mass index:
      29.9 +/- 4.9 kg/m(2); apnea-hypopnea index: 41.3 +/- 17.5/h; cardiovascular risk
      score: 13.5 +/- 3.7%) were included. Physical activity and sedentary behaviors
      were objectively assessed by actigraphy, and self-measured home BP monitoring was
      measured. Logistic regression models adjusted for sex, age, and body mass index
      were built to identify the predictors of self-measured morning and evening BP.
      RESULTS: Physical activity was significantly related to obesity but not to the
      severity of sleep apnea or sleepiness. Sedentary behaviors were associated with
      self-measured morning and evening systolic BP (r = 0.32, P = .002; r = 0.29, P =
      .004). Steps per day were inversely associated with evening BP (r = -0.27, P =
      .01). Univariate analysis identified steps/d and time spent in vigorous physical
      activity as determinants for evening self-measured BP. In multivariate analysis,
      only steps/d were identified as a significant determinant of evening BP.
      CONCLUSIONS: Physical activity is the major determinant for evening BP in adults
      with OSA presenting high cardiovascular risk. Our results emphasize the need for
      lifestyle counseling programs in combination with CPAP to encourage regular
      physical activity in OSA subjects to obtain better BP control.
      (ClinicalTrials.gov registration NCT01226641.)

PMID- 24282317
TI  - The modified integrative weaning index as a predictor of extubation failure.
AB  - INTRODUCTION: The extubation period is one of the most challenging aspects for
      intensive care teams. Timely recognition of the return to spontaneous ventilation
      is essential for reducing costs, morbidity, and mortality. Several weaning
      predictors were studied in an attempt to evaluate the outcome of removing
      ventilatory support. The purpose of this study was to analyze the predictive
      performance of the modified integrative weaning index (IWI) in the extubation
      process. METHODS: A prospective study was performed in an ICU in a public
      hospital in Porto Alegre, Brazil, with 59 adult medical-surgical beds. The final
      population of the study comprised 153 patients receiving mechanical ventilation
      for over 48 h who were extubated during the period from February to November
      2011. Demographic data and clinical parameters were collected in addition to
      extubation predictors, including static compliance of the respiratory system,
      ratio of breathing frequency to tidal volume, tracheal airway-occlusion pressure
      0.1 s after the start of inspiratory flow, and modified IWI. RESULTS: Extubation
      failure was observed in 23 of the subjects (15%). Subjects with greater positive
      fluid balance, lower hemoglobin levels, and lower levels of bicarbonate presented
      a higher rate of reintubation. The 3 modified IWI values (the first and 30th
      minute of the spontaneous breathing trial and the difference between them), as
      well as the other ventilatory parameters and extubation predictors, displayed
      poor extubation outcome discrimination accuracy. All indexes presented small
      areas under the receiver operating characteristic curve, and no accurate cutoff
      point was identified. CONCLUSIONS: We concluded that modified IWI, similar to
      other extubation predictors, does not accurately predict extubation failure.

PMID- 24282318
TI  - Maintenance of airway pressure during filter exchange due to auto-triggering.
AB  - BACKGROUND: Daily routine ventilator-filter exchange interrupts the integrity of
      the ventilator circuit. We hypothesized that this might reduce positive airway
      pressure in mechanically ventilated ICU patients, inducing alveolar collapse and
      causing impaired oxygenation and compliance of the respiratory system. METHODS:
      We studied 40 consecutive ICU subjects (P(aO2)/F(IO2) ratio <= 300 mm Hg),
      mechanically ventilated with pressure-regulated volume control or pressure
      support and PEEP >= 5 cm H2O. Before the filter exchange, (baseline) tidal
      volume, breathing frequency, end-inspiratory plateau pressure, and PEEP were
      recorded. Compliance of the respiratory system was calculated; F(IO2), blood
      pressure, and pulse rate were registered; and P(aO2), P(aCO2), pH, and base
      excess were measured. Measurements were repeated 15 and 60 min after the filter
      exchange. In addition, a bench test was performed with a precision test lung with
      similar compliance and resistance as in the clinical study. RESULTS: The exchange
      of the filter took 3.5 +/- 1.2 s (mean +/- SD). There was no significant change
      in P(aO2) (89 +/- 16 mm Hg at baseline vs 86 +/- 16 mm Hg at 15 min and 88 +/- 18
      mm Hg at 60 min, P = .24) or in compliance of the respiratory system (41 +/- 11
      mL/cm H2O at baseline vs 40 +/- 12 mL/cm H2O at 15 min and 40 +/- 12 mL/cm H2O at
      60 min, P = .32). The bench study showed that auto-triggering by the ventilator
      when disconnecting from the expiratory circuit kept the tracheal pressure above
      PEEP for at least 3 s with pressure controlled ventilation. CONCLUSIONS: This
      study showed that a short disconnection of the expiratory ventilator circuit from
      the ventilator during filter exchange was not associated with any significant
      deterioration in lung function 15 and 60 min later. This result may be explained
      by auto-triggering of the ventilator with high inspiratory flows during the
      filter exchange, maintaining airway pressure.

PMID- 24282319
TI  - Rituximab for induction and maintenance treatment of ANCA-associated
      vasculitides: a multicentre retrospective study on 80 patients.
AB  - OBJECTIVES: Rituximab has been shown to induce remission of ANCA-associated
      vasculitides (AAVs). Our study was undertaken to describe AAV clinical responses
      to rituximab used for remission-induction and/or maintenance therapy, assess
      rituximab's safety profile and evaluate French clinical practices. METHODS: This
      retrospective study concerned AAV patients who had received one or more rituximab
      infusion between 2002 and January 2011 and had follow-up lasting >=12 months.
      RESULTS: Eighty patients were included, most with refractory or relapsing AAV: 70
      (88%) with granulomatosis with polyangiitis (GPA), 9 (11%) with microscopic
      polyangiitis and 1 (1%) with eosinophilic GPA. Rituximab was the first agent used
      to induce remission in 73 patients. The two most commonly administered regimens
      were an infusion of 375 mg/m(2)/week for 4 weeks (54 patients) and an infusion of
      1 g every 2 weeks for a month (16 patients). Rituximab was first prescribed to
      maintain remission in seven patients. Respective 1-, 2-, and 3-year relapse-free
      survival rates after the first infusion were 80% (95% CI 72, 89), 63% (51, 77)
      and 52% (39, 70). Relapse-free survival was longer for patients receiving
      rituximab maintenance therapy (P = 0.002). Among 22 (28%) rituximab-treated
      patients experiencing severe adverse events, 12 (15%) had infectious
      complications leading to 4 (5%) deaths. Only 15 (19%) patients had received anti
      pneumococcal vaccine before rituximab. CONCLUSION: Rituximab was able to induce
      AAV remission and seemed to maintain remission better than other agents, but
      caution is needed concerning its safety, especially regarding bacterial
      infections, in this population.

PMID- 24282320
TI  - Review of Bayesian statistical analysis methods for cytogenetic radiation
      biodosimetry, with a practical example.
AB  - Classical methods of assessing the uncertainty associated with radiation doses
      estimated using cytogenetic techniques are now extremely well defined. However,
      several authors have suggested that a Bayesian approach to uncertainty estimation
      may be more suitable for cytogenetic data, which are inherently stochastic in
      nature. The Bayesian analysis framework focuses on identification of probability
      distributions (for yield of aberrations or estimated dose), which also means that
      uncertainty is an intrinsic part of the analysis, rather than an 'afterthought'.
      In this paper Bayesian, as well as some more advanced classical, data analysis
      methods for radiation cytogenetics are reviewed that have been proposed in the
      literature. A practical overview of Bayesian cytogenetic dose estimation is also
      presented, with worked examples from the literature. 

PMID- 24282321
TI  - Report on the 2nd International Consortium on Hallucination Research: evolving
      directions and top-10 "hot spots" in hallucination research.
AB  - This article presents a report on the 2nd meeting of the International Consortium
      on Hallucination Research, held on September 12th and 13th 2013 at Durham
      University, UK. Twelve working groups involving specialists in each area
      presented their findings and sought to summarize the available knowledge,
      inconsistencies in the field, and ways to progress. The 12 working groups
      reported on the following domains of investigation: cortical organisation of
      hallucinations, nonclinical hallucinations, interdisciplinary approaches to
      phenomenology, culture and hallucinations, subtypes of auditory verbal
      hallucinations, a Psychotic Symptoms Rating Scale multisite study, visual
      hallucinations in the psychosis spectrum, hallucinations in children and
      adolescents, Research Domain Criteria behavioral constructs and hallucinations,
      new methods of assessment, psychological therapies, and the Hearing Voices
      Movement approach to understanding and working with voices. This report presents
      a summary of this meeting and outlines 10 hot spots for hallucination research,
      which include the in-depth examination of (1) the social determinants of
      hallucinations, (2) translation of basic neuroscience into targeted therapies,
      (3) different modalities of hallucination, (4) domain convergence in cross
      diagnostic studies, (5) improved methods for assessing hallucinations in
      nonclinical samples, (6) using humanities and social science methodologies to
      recontextualize hallucinatory experiences, (7) developmental approaches to better
      understand hallucinations, (8) changing the memory or meaning of past trauma to
      help recovery, (9) hallucinations in the context of sleep and sleep disorders,
      and (10) subtypes of hallucinations in a therapeutic context. 

PMID- 24282322
TI  - Impact of interpersonal trauma on the social functioning of adults with first
      episode psychosis.
AB  - BACKGROUND: Social functioning is an important treatment outcome for psychosis,
      and yet, we know little about its relationship to trauma despite high rates of
      trauma in people with psychosis. Childhood trauma is likely to disrupt the
      acquisition of interpersonal relatedness skills including the desire for
      affiliation and thus lead to impaired social functioning in adulthood. AIMS: We
      hypothesized that childhood trauma would be a predictor of poor social
      functioning for adults with psychosis and that further trauma in adulthood would
      moderate this relationship. METHOD: A first-episode psychosis sample aged 15-65
      years (N = 233) completed measures of social functioning (Lehman's Quality of
      Life Interview and Strauss Carpenter Functioning Scale) and trauma (Brief
      Betrayal Trauma Survey), as well as clinical assessments. RESULTS: Childhood
      trauma (any type) was associated with poorer premorbid functioning and was
      experienced by 61% of our sample. There were no associations with clinical
      symptoms. Interpersonal trauma in childhood was a significant predictor of social
      functioning satisfaction in adulthood, but this was not the case for
      interpersonal trauma in adulthood. However, 45% of adults who reported childhood
      interpersonal trauma also experienced adulthood interpersonal trauma. CONCLUSION:
      Our results emphasize the importance of early relationship experience such as
      interpersonal trauma, on the social functioning of adults with psychosis. We
      recommend extending our research by examining the impact of interpersonal
      childhood trauma on occupational functioning in psychosis.

PMID- 24282324
TI  - What happens in "chromospheres"?

PMID- 24282323
TI  - Anatomical distance affects functional connectivity in patients with
      schizophrenia and their siblings.
AB  - BACKGROUND: The efficiency of human brain depends on the integrity of both long-
      and short-range connections, but the long-range connections need to be
      "penalized" to reduce overall wiring costs. This principle, termed as the
      anatomical distance function (ADF), refers to the presence of an inverse
      relationship between anatomical distance and connectivity. A crucial
      developmental feature that occurs in normal adolescence is the weakening of ADF,
      which is characterized by a selective strengthening of long-distance connections.
      Schizophrenia is associated with widespread dysconnectivity that is linked to
      aberrant cortical development. METHODS: We studied the ADF in adults with
      schizophrenia (n = 28), their age-matched siblings (n = 28), and healthy controls
      (n = 60). We investigated the proportional abnormalities in the long-range
      connections involving interhemispheric, subcortical, frontal, and salience
      network regions and localized the connections showing most significant changes in
      schizophrenia. The groups were discriminated on the basis of short- and long
      range connectivity using a machine-learning algorithm. RESULTS: Both patients and
      their siblings showed abnormally pronounced ADF. This was associated with a
      disproportionate reduction in the number of long-range connections, affecting the
      subcortical, interhemispheric, and the salience network connections. The
      abnormalities in long-range connections had superior ability to accurately
      identify group membership. CONCLUSIONS: A crucial organizing principle of the
      brain architecture that becomes apparent during normal adolescence is disturbed
      in schizophrenia. While siblings show some evidence of compensating for this
      deficit, patients lack putative compensatory changes. Age-related shift in ADF
      provides an explanatory framework for the developmental emergence of widespread
      dysconnectivity that is influenced by genetic risk in schizophrenia.

PMID- 24282325
TI  - Progenitor cells in chromospheres: in response to Arthur S. Tischler.

PMID- 24282329
TI  - HIV and syphilis infection in pregnant women in Ecuador: prevalence and
      characteristics of antenatal care.
AB  - OBJECTIVES: This study aimed to obtain nationally representative estimates of HIV
      and syphilis prevalence and coverage of preventive antenatal services in pregnant
      women in Ecuador, in order to develop a national strategy for the elimination of
      mother-to-child transmission of HIV and syphilis. METHODS: A national probability
      sample of 5988 women presenting for delivery or miscarriage services was selected
      from 15 healthcare facilities during 2011-2012, using a two-stage cluster sample
      technique. Biological specimens were collected and an interview and review of
      medical records were performed. Agreement between these last two sources was
      measured. Estimates were adjusted for the sampling design. RESULTS: Estimated
      national HIV prevalence (0.60%) was higher than confirmed syphilis infection
      prevalence (0.25%). In the coastal region, HIV prevalence (1.13%) exceeded the
      threshold that defines a generalised epidemic and syphilis prevalence reached
      0.37%. An estimated 5.9% of women did not use antenatal care services while 73.0%
      completed at least four consultations. HIV testing coverage (89.9%) was higher
      than for syphilis (71.6%). Agreement between medical records and interviews was
      mostly moderate (0.40-0.75). Important variables were frequently not recorded,
      such as timing of syphilis testing, which was not recorded in 49.6%. CONCLUSIONS:
      The concentration of HIV and syphilis infections in the coastal region of Ecuador
      highlights the need for intensified prevention and a response tailored to local
      epidemic conditions. Major challenges for the elimination initiative include
      achieving universal, early access to antenatal care, improving coverage of HIV
      and syphilis testing, and improving the quality of medical records to support
      progress monitoring.

PMID- 24282330
TI  - What's new about Natsal-3?

PMID- 24282331
TI  - A compact high-resolution X-ray powder diffractometer.
AB  - A new powder diffractometer operating in transmission mode is described. It can
      work as a rapid very compact instrument or as a high-resolution instrument, and
      the sample preparation is simplified. The incident beam optics create pure Cu
      Kalpha1 radiation, giving rise to peak widths of ~0.1 degrees  in 2theta in
      compact form with a sample-to-detector minimum radius of 55 mm, reducing to peak
      widths of <0.05 degrees  in high-resolution mode by increasing the detector
      radius to 240 mm. The resolution of the diffractometer is shown to be governed by
      a complex mixture of angular divergence, sample size, diffraction effects and the
      dimensions of the detector pixels. The data can be collected instantaneously,
      which combined with trivial sample preparation and no sample alignment, makes it
      a suitable method for very rapid phase identification. As the detector is moved
      further from the sample, the angular step from the pixel dimension is reduced and
      the resolution improves significantly for very detailed studies, including
      structure determination and analysis of the microstructure. The advantage of this
      geometry is that the resolution of the diffractometer can be calculated precisely
      and the instrumental artefacts can be analysed easily without a sample present.
      The performance is demonstrated with LaB6 and paracetamol, and a critical
      appraisal of the uncertainties in the measurements is presented. The
      instantaneous data collection offers possibilities in dynamic experiments.

PMID- 24282332
TI  - The interpretation of polycrystalline coherent inelastic neutron scattering from
      aluminium.
AB  - A new approach to the interpretation and analysis of coherent inelastic neutron
      scattering from polycrystals (poly-CINS) is presented. This article describes a
      simulation of the one-phonon coherent inelastic scattering from a lattice model
      of an arbitrary crystal system. The one-phonon component is characterized by
      sharp features, determined, for example, by boundaries of the (Q, omega) regions
      where one-phonon scattering is allowed. These features may be identified with the
      same features apparent in the measured total coherent inelastic cross section,
      the other components of which (multiphonon or multiple scattering) show no sharp
      features. The parameters of the model can then be relaxed to improve the fit
      between model and experiment. This method is of particular interest where no
      single crystals are available. To test the approach, the poly-CINS has been
      measured for polycrystalline aluminium using the MARI spectrometer (ISIS),
      because both lattice dynamical models and measured dispersion curves are
      available for this material. The models used include a simple Lennard-Jones model
      fitted to the elastic constants of this material plus a number of embedded atom
      method force fields. The agreement obtained suggests that the method demonstrated
      should be effective in developing models for other materials where single-crystal
      dispersion curves are not available.

PMID- 24282333
TI  - Fibrinogen species as resolved by HPLC-SAXS data processing within the UltraScan
      Solution Modeler (US-SOMO) enhanced SAS module.
AB  - Fibrinogen is a large heterogeneous aggregation/degradation-prone protein playing
      a central role in blood coagulation and associated pathologies, whose structure
      is not completely resolved. When a high-molecular-weight fraction was analyzed by
      size-exclusion high-performance liquid chromatography/small-angle X-ray
      scattering (HPLC-SAXS), several composite peaks were apparent and because of the
      stickiness of fibrinogen the analysis was complicated by severe capillary
      fouling. Novel SAS analysis tools developed as a part of the UltraScan Solution
      Modeler (US-SOMO; http://somo.uthscsa.edu/), an open-source suite of utilities
      with advanced graphical user interfaces whose initial goal was the hydrodynamic
      modeling of biomacromolecules, were implemented and applied to this problem. They
      include the correction of baseline drift due to the accumulation of material on
      the SAXS capillary walls, and the Gaussian decomposition of non-baseline-resolved
      HPLC-SAXS elution peaks. It was thus possible to resolve at least two species co
      eluting under the fibrinogen main monomer peak, probably resulting from in-column
      degradation, and two others under an oligomers peak. The overall and cross
      sectional radii of gyration, molecular mass and mass/length ratio of all species
      were determined using the manual or semi-automated procedures available within
      the US-SOMO SAS module. Differences between monomeric species and linear and
      sideways oligomers were thus identified and rationalized. This new US-SOMO
      version additionally contains several computational and graphical tools,
      implementing functionalities such as the mapping of residues contributing to
      particular regions of P(r), and an advanced module for the comparison of primary
      I(q) versus q data with model curves computed from atomic level structures or
      bead models. It should be of great help in multi-resolution studies involving
      hydrodynamics, solution scattering and crystallographic/NMR data.

PMID- 24282334
TI  - Three-dimensional rotation electron diffraction: software RED for automated data
      collection and data processing.
AB  - Implementation of a computer program package for automated collection and
      processing of rotation electron diffraction (RED) data is described. The software
      package contains two computer programs: RED data collection and RED data
      processing. The RED data collection program controls the transmission electron
      microscope and the camera. Electron beam tilts at a fine step (0.05-0.20 degrees
      ) are combined with goniometer tilts at a coarse step (2.0-3.0 degrees ) around a
      common tilt axis, which allows a fine relative tilt to be achieved between the
      electron beam and the crystal in a large tilt range. An electron diffraction (ED)
      frame is collected at each combination of beam tilt and goniometer tilt. The RED
      data processing program processes three-dimensional ED data generated by the RED
      data collection program or by other approaches. It includes shift correction of
      the ED frames, peak hunting for diffraction spots in individual ED frames and
      identification of these diffraction spots as reflections in three dimensions.
      Unit-cell parameters are determined from the positions of reflections in three
      dimensional reciprocal space. All reflections are indexed, and finally a list
      with hkl indices and intensities is output. The data processing program also
      includes a visualizer to view and analyse three-dimensional reciprocal lattices
      reconstructed from the ED frames. Details of the implementation are described.
      Data collection and data processing with the software RED are demonstrated using
      a calcined zeolite sample, silicalite-1. The structure of the calcined silicalite
      1, with 72 unique atoms, could be solved from the RED data by routine direct
      methods.

PMID- 24282335
TI  - Characterization of salt interferences in second-harmonic generation detection of
      protein crystals.
AB  - Studies were undertaken to assess the merits and limitations of second-harmonic
      generation (SHG) for the selective detection of protein and polypeptide crystal
      formation, focusing on the potential for false positives from SHG-active salts
      present in crystallization media. The SHG activities of salts commonly used in
      protein crystallization were measured and quantitatively compared with reference
      samples. Out of 19 salts investigated, six produced significant background SHG
      and 15 of the 96 wells of a sparse-matrix screen produced SHG upon solvent
      evaporation. SHG-active salts include phosphates, hydrated sulfates, formates and
      tartrates, while chlorides, acetates and anhydrous sulfates resulted in no
      detectable SHG activity. The identified SHG-active salts produced a range of
      signal intensities spanning nearly three orders of magnitude. However, even the
      weakest SHG-active salt produced signals that were several orders of magnitude
      greater than those produced by typical protein crystals. In general, SHG-active
      salts were identifiable through characteristically strong SHG and negligible two
      photon-excited ultraviolet fluorescence (TPE-UVF). Exceptions included trials
      containing either potassium dihydrogen phosphate or ammonium formate, which
      produced particularly strong SHG, but with residual weak TPE-UVF signals that
      could potentially complicate discrimination in crystallization experiments using
      these precipitants.

PMID- 24282336
TI  - Gender differences in the motivational processing of facial beauty.
AB  - Gender may be involved in the motivational processing of facial beauty. This
      study applied a behavioral probe, known to activate brain motivational regions,
      to healthy heterosexual subjects. Matched samples of men and women were
      administered two tasks: (a) key pressing to change the viewing time of average or
      beautiful female or male facial images, and (b) rating the attractiveness of
      these images. Men expended more effort (via the key-press task) to extend the
      viewing time of the beautiful female faces. Women displayed similarly increased
      effort for beautiful male and female images, but the magnitude of this effort was
      substantially lower than that of men for beautiful females. Heterosexual facial
      attractiveness ratings were comparable in both groups. These findings demonstrate
      heterosexual specificity of facial motivational targets for men, but not for
      women. Moreover, heightened drive for the pursuit of heterosexual beauty in the
      face of regular valuational assessments, displayed by men, suggests a gender
      specific incentive sensitization phenomenon.

PMID- 24282337
TI  - Tissue kidney injury molecule-1 expression in the prediction of renal function
      for several years after kidney biopsy.
AB  - OBJECTIVES: Retrospective study was designed to examine the importance of tissue
      kidney injury molecule-1 (KIM-1) expression in predicting kidney function in
      sixty patients (27 males) aged 34.15 +/- 12.23 years with different kidney
      diseases over three years after kidney biopsy. MATERIALS AND METHODS: Tissue KIM
      1 expression was determined immunohistochemically and KIM-1 staining was scored
      semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy,
      and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated
      at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later. RESULTS:
      Significantly positive correlations between tissue KIM-1 expression and age (r =
      0.313), TIN inflammation (r = 0.456), fibrosis (r = 0.317), and proteinuria at 6
      months (r = 0.394) as well as negative correlations with GFR0 (r = -0.572), GFR6
      (r = -0.442), GFR24 (r = -0.398), and GFR36 (r = -0.412) were found. Meanwhile,
      TIN inflammation was the best predictor of all measured kidney functions during
      three years, while tissue KIM-1 expression (P = 0.016) was a predictor only at 6
      months after biopsy. CONCLUSION: Tissue KIM-1 expression significantly predicts
      kidney function solely at 6 months after biopsy, when the effects of immune and
      nonimmune treatments are the strongest.

PMID- 24282338
TI  - CD90- (Thy-1-) high selection enhances reprogramming capacity of murine adipose
      derived mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs), including adipose tissue-derived
      mesenchymal stem cells (ADSC), are multipotent and can differentiate into various
      cell types possessing unique immunomodulatory features. Several clinical trials
      have demonstrated the safety and possible efficacy of MSCs in organ
      transplantation. Thus, stem cell therapy is promising for tolerance induction. In
      this study, we assessed the reprogramming capacity of murine ADSCs and found that
      CD90 (Thy-1), originally discovered as a thymocyte antigen, could be a useful
      marker for cell therapy. METHOD: Murine ADSCs were isolated from B6 mice, sorted
      using a FACSAria cell sorter by selection of CD90(Hi) or CD90(Lo), and then
      transduced with four standard factors (4F; Oct4, Sox2, Klf4, and c-Myc). RESULTS:
      Unsorted, CD90(Hi)-sorted, and CD90(Lo)-sorted murine ADSCs were reprogrammed
      using standard 4F transduction. CD90(Hi) ADSCs showed increased numbers of
      alkaline phosphatase-positive colonies compared with CD90(Lo) ADSCs. The relative
      reprogramming efficiencies of unsorted, CD90(Hi)-sorted, and CD90(Lo)-sorted
      ADSCs were 100%, 116.5%, and 74.7%, respectively. CD90(Hi) cells were more
      responsive to reprogramming. CONCLUSION: CD90(Hi) ADSCs had greater reprogramming
      capacity than CD90(Lo) ADSCs, suggesting that ADSCs have heterogeneous
      subpopulations. Thus, CD90(Hi) selection presents an effective strategy to
      isolate a highly suppressive subpopulation for stem cell-based tolerance
      induction therapy.

PMID- 24282339
TI  - Inhibition of cathepsin S produces neuroprotective effects after traumatic brain
      injury in mice.
AB  - Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has
      long been regarded as an enzyme that is primarily involved in general protein
      degradation. More recently, mounting evidence has shown that it is involved in
      Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic
      pain. In this study, we investigated the time course of CatS protein and mRNA
      expression and the cellular distribution of CatS in a mouse model of traumatic
      brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice
      intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor,
      and examined the effect on inflammation and neurobehavioral function. We found
      that expression of CatS was increased as early as 1 h after TBI at both protein
      and mRNA levels. The increased expression was detected in microglia and neurons.
      Inhibition of CatS significantly reduced the level of TBI-induced inflammatory
      factors in brain tissue and alleviated brain edema. Additionally, administration
      of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral
      function. These results imply that CatS is involved in the secondary injury after
      TBI and provide a new perspective for preventing secondary injury after TBI. 

PMID- 24282340
TI  - Implication of low HDL-c levels in patients with average LDL-c levels: a focus on
      oxidized LDL, large HDL subpopulation, and adiponectin.
AB  - To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL
      c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and
      inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and
      control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and
      the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist
      circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c
      and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1)
      activity, hsCRP, uric acid, TNF- alpha , adiponectin, VEGF, and iCAM1. In the
      control subgroup with low HDL-c levels, significantly higher values of BP and TGs
      and lower values of PON1 activity and adiponectin were found, versus control
      normal HDL-c subgroup. However, differences in patients' subgroups were clearly
      more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non
      HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large
      HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting
      correlations with classical and nonclassical markers, mainly in the normal HDL-c
      patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c
      concentrations seem to be associated with a poor cardiometabolic profile in a
      population with cardiovascular risk factors, which is better evidenced by
      traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and
      adiponectin. 

PMID- 24282341
TI  - High intensity focused ultrasound, liver disease and bridging therapy.
AB  - High-intensity focused ultrasound (HIFU) is a non-invasive modality that uses an
      extracorporeal source of focused ultrasound energy. This technique was introduced
      by Lynn et al and is able to induce coagulative necrosis in selected tissues
      without damaging adjacent structures. Although HIFU has been studied for 50
      years, recent technological developments now allow its use for tumours of the
      liver, prostate and other sites. In liver disease, HIFU has been used to treat
      unresectable, advanced stages of hepatocellular carcinoma (HCC) and liver
      metastases. Hepatocellular carcinoma is a serious health problem worldwide and is
      endemic in some areas because of its association with hepatitis B and C viruses
      (in 20% of cases). Liver transplantation (LT) has become one of the best
      treatments available because it removes both the tumour and the underlying liver
      disease such as cirrhosis (which is present in approximately 80% of cases). The
      prerequisite for long-term transplant success depends on tumour load and strict
      selection criteria regarding the size and number of tumour nodules. The need to
      obtain the optimal benefit from the limited number of organs available has
      prompted strict selection criteria limited to only those patients with early HCC
      who have a better long-term outcome after LT. The so-called "bridging therapy"
      has the aim of controlling disease burden for patients who are on the organ
      transplant waiting list. Amongst various treatment options, transarterial
      chemoembolisation and radiofrequency ablation are the most popular treatment
      choices. Recently, Cheung et al demonstrated that HIFU ablation is a safe and
      effective method for the treatment of HCC patients with advanced cirrhosis as a
      bridging therapy and that it reduced the dropout rate from the liver transplant
      waiting list. In this commentary, we discuss the current value of HIFU in the
      treatment of liver disease, including its value as a bridging therapy, and
      examine the potential advantages of other therapeutic strategies. 

PMID- 24282342
TI  - Role of innate immunity in the development of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide.
      It is caused by a variety of risk factors, most common ones being infection with
      hepatitis viruses, alcohol, and obesity. HCC often develops in the background of
      underlying cirrhosis, and even though a number of interventional treatment
      methods are currently in use, recurrence is fairly common among patients who have
      had a resection. Therefore, whole liver transplantation remains the most
      practical treatment option for HCC. Due to the growing incidence of HCC, intense
      research efforts are being made to understand cellular and molecular mechanisms
      of the disease so that novel therapeutic strategies can be developed to combat
      liver cancer. In recent years, it has become clear that innate immunity plays a
      critical role in the development of a number of liver diseases, including HCC. In
      particular, the activation of Toll-like receptor signaling results in the
      generation of immune responses that often results in the production of pro
      inflammatory cytokines and chemokines, and could cause acute inflammation in the
      liver. In this review, the current knowledge on the role of innate immune
      responses in the development and progression of HCC is examined, and emerging
      therapeutic strategies based on molecular mechanisms of HCC are discussed. 

PMID- 24282344
TI  - Beyond white light endoscopy: the role of optical biopsy in inflammatory bowel
      disease.
AB  - In this review, we will discuss the use of two optical biopsy modalities in
      inflammatory bowel disease (IBD). The two techniques reviewed here are confocal
      laser endomicroscopy and endocytoscopy. We will describe the technical
      performance of the procedure, discuss the clinical indications for optical biopsy
      in IBD, and highlight active research areas with respect to the pathogenesis of
      IBD. Clinical indications for optical biopsies in IBD include assessment of
      mucosal inflammation, dysplasia detection and evaluation of cell shedding for
      disease relapse. Research application in the area of barrier dysfunction will
      also be discussed. 

PMID- 24282343
TI  - Bridging and downstaging treatments for hepatocellular carcinoma in patients on
      the waiting list for liver transplantation.
AB  - Several therapeutic procedures have been proposed as bridging treatments for
      patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT).
      The most used treatments include transarterial chemoembolization and
      radiofrequency ablation. Surgical resection has also been successfully used as a
      bridging procedure, and LT should be considered a rescue treatment in patients
      with previous HCC resection who experience tumor recurrence or post-treatment
      severe decompensation of liver function. The aims of bridging treatments include
      decreasing the waiting list dropout rate before transplantation, reducing HCC
      recurrence after transplantation, and improving post-transplant overall survival.
      To date, no data from prospective randomized studies are available; however, for
      HCC patients listed for LT within the Milan criteria, prolonging the waiting time
      over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in
      containing tumor progression and decreasing dropout. Furthermore, the response to
      pre-LT treatments may represent a surrogate marker of tumor biological
      aggressiveness and could therefore be evaluated to prioritize HCC candidates for
      LT. Lastly, although a definitive conclusion can not be reached, the experiences
      reported to date suggest a positive impact of these treatments on both tumor
      recurrence and post-transplant patient survival. Advanced HCC may be downstaged
      to achieve and maintain the current conventional criteria for inclusion in the
      waiting list for LT. Recent studies have demonstrated that successfully
      downstaged patients can achieve a 5-year survival rate comparable to that of
      patients meeting the conventional criteria without requiring downstaging. 

PMID- 24282345
TI  - Mucosal healing and deep remission: what does it mean?
AB  - The use of specific terms under different meanings and varying definitions has
      always been a source of confusion in science. When we point our efforts towards
      an evidence based medicine for inflammatory bowel diseases (IBD) the same is
      true: Terms such as "mucosal healing" or "deep remission" as endpoints in
      clinical trials or treatment goals in daily patient care may contribute to
      misconceptions if meanings change over time or definitions are altered. It
      appears to be useful to first have a look at the development of terms and their
      definitions, to assess their intrinsic and context-independent problems and then
      to analyze the different relevance in present-day clinical studies and trials.
      The purpose of such an attempt would be to gain clearer insights into the true
      impact of the clinical findings behind the terms. It may also lead to a better
      defined use of those terms for future studies. The terms "mucosal healing" and
      "deep remission" have been introduced in recent years as new therapeutic targets
      in the treatment of IBD patients. Several clinical trials, cohort studies or
      inception cohorts provided data that the long term disease course is better, when
      mucosal healing is achieved. However, it is still unclear whether continued or
      increased therapeutic measures will aid or improve mucosal healing for patients
      in clinical remission. Clinical trials are under way to answer this question.
      Attention should be paid to clearly address what levels of IBD activity are
      looked at. In the present review article authors aim to summarize the current
      evidence available on mucosal healing and deep remission and try to highlight
      their value and position in the everyday decision making for gastroenterologists.

PMID- 24282346
TI  - Has the risk of colorectal cancer in inflammatory bowel disease decreased?
AB  - The association between inflammatory bowel disease (IBD) and colorectal cancer
      (CRC) has been acknowledged for almost a century and is assumedly promoted by a
      chronic inflammation-driven carcinogenic process in the intestine in combination
      with a genetic predisposition. The magnitude of the risk of CRC in IBD remains a
      continuing subject of debate. The early, high risk estimates for CRC in IBD were
      most likely overestimated due to selected patient populations originating from
      tertiary referral centers with a disproportional high percentage of patients with
      severe disease. Later population-based studies calculating risk estimates from a
      broad spectrum of IBD patients have found the risk to be significantly lower. At
      present, there is evidence that IBD patients with longstanding and extensive
      disease with uncontrolled inflammation are those at increased risk. Additional,
      other recognized risk factors include early age at onset, family history of CRC,
      and concomitant primary sclerosing cholangitis. A significant amount of effort is
      put into identifying potential preventive factors of CRC in IBD, including
      surveillance programs and chemopreventive agents but the individual effect of
      these remains uncertain. Interestingly, recent studies have reported a decline in
      risk of CRC over time. Surveillance programs and the new treatment strategies,
      particular biological treatment might be part of the reason for the observed
      decline in risk of CRC in IBD over time but future studies will have investigate
      this assumption. 

PMID- 24282347
TI  - Autoantibodies and an immune-based rat model of inflammatory bowel disease.
AB  - The exact causes of inflammatory bowel disease (IBD) are not yet fully defined.
      From a vast body of literature, we know that the immune response has long been
      involved in the pathogenesis of IBD, including both ulcerative colitis and
      Crohn's disease. A variety of specific alterations can lead to immune activation
      and inflammation directed to the colon, as revealed by some animal models.
      Current research has focused on the role of antibodies in downstream events and
      mechanisms of autoimmunity and inflammation. It is not well known whether the
      production of antibodies is a serologic consequence of IBD, or if it is a result
      of barrier dysfunction induced by inflammation. Here, we present a new hypothesis
      to distinguish the complex links between genetic susceptibility, barrier
      dysfunction, commensal and pathologic microbial factors and inflammatory response
      (especially autoantibodies) in the pathogenesis of IBD. To ascertain the
      hypothesis, we developed a pilot model with the concept of the presence of
      antibodies against enteric bacterial antigens in IBD. Results confirmed our
      hypothesis. Our hypothesis suggests the possibility of subcutaneous vaccination
      of animals with administration of all or specific enteric bacterial antigens. 

PMID- 24282348
TI  - Clostridium difficile and inflammatory bowel disease: role in pathogenesis and
      implications in treatment.
AB  - Clostridium difficile (C. difficile) is the leading cause of antibiotic
      associated colitis and nosocomial diarrhea. Patients with inflammatory bowel
      disease (IBD) are at increased risk of developing C. difficile infection (CDI),
      have worse outcomes of CDI-including higher rates of colectomy and death, and
      experience higher rates of recurrence. However, it is still not clear whether C.
      difficile is a cause of IBD or a consequence of the inflammatory state in the
      intestinal environment. The burden of CDI has increased dramatically over the
      past decade, with severe outbreaks described in many countries, which have been
      attributed to a new and more virulent strain. A parallel rise in the incidence of
      CDI has been noted in patients with IBD. IBD patients with CDI tend be younger,
      have less prior antibiotic exposure, and most cases of CDI in these patients
      represent outpatient acquired infections. The clinical presentation of CDI in
      these patients can be unique-including diversion colitis, enteritis and
      pouchitis, and typical findings on colonoscopy are often absent. Due to the high
      prevalence of CDI in patients hospitalized with an IBD exacerbation, and the
      prognostic implications of CDI in these patients, it is recommended to test all
      IBD patients hospitalized with a disease flare for C. difficile. Treatment
      includes general measures such as supportive care and infection control measures.
      Antibiotic therapy with either oral metronidazole, vancomycin, or the novel
      antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota
      transplantation constitutes another optional treatment for severe/recurrent CDI.
      The aim of this paper is to review recent data on CDI in IBD: role in
      pathogenesis, diagnostic methods, optional treatments, and outcomes of these
      patients. 

PMID- 24282349
TI  - Extravascular use of drug-eluting beads: a promising approach in compartment
      based tumor therapy.
AB  - Intraperitoneal carcinomatosis (PC) may occur with several tumor entities. The
      prognosis of patients suffering from PC is usually poor. Present treatment
      depends on the cancer entity and includes systemic chemotherapy, radiation
      therapy, hormonal therapy and surgical resection. Only few patients may also
      benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor
      remission. These therapies are often accompanied by severe systemic side-effects.
      One approach to reduce side effects is to target chemotherapeutic agents to the
      tumor with carrier devices. Promising experimental results have been achieved
      using drug-eluting beads (DEBs). A series of in vitro and in vitro experiments
      has been conducted to determine the suitability of their extravascular use. These
      encapsulation devices were able to harbor CYP2B1 producing cells and to shield
      them from the hosts immune system when injected intratumorally. In this way
      ifosfamide--which is transformed into its active metabolites by CYP2B1--could be
      successfully targeted into pancreatic tumor growths. Furthermore DEBs can be used
      to target chemotherapeutics into the abdominal cavity for treatment of PC. If
      CYP2B1 producing cells are proven to be save for usage in man and if local toxic
      effects of chemotherapeutics can be controlled, DEBs will become promising tools
      in compartment-based anticancer treatment.

PMID- 24282350
TI  - Rare cystic liver lesions: a diagnostic and managing challenge.
AB  - Cystic formations within the liver are a frequent finding among populations.
      Besides the common cystic lesions, like simple liver cysts, rare cystic liver
      lesions like cystadenocarcinoma should also be considered in the differential
      diagnosis. Thorough knowledge of each entity's nature and course are key elements
      to successful treatment. Detailed search in PubMed, Cochrane Database, and
      international published literature regarding rare cystic liver lesions was
      carried out. In our research are included not only primary rare lesions like
      cystadenoma, hydatid cyst, and polycystic liver disease, but also secondary ones
      like metastasis from gastrointestinal stromal tumors lesions. Up-to date
      knowledge regarding diagnosis and management of rare cystic liver lesions is
      provided. A diagnostic and therapeutic algorithm is also proposed. The need for a
      multidisciplinary approach by a team including radiologists and surgeons familiar
      with liver cystic entities, diagnostic tools, and treatment modalities is
      stressed. Patients with cystic liver lesions must be carefully evaluated by a
      multidisciplinary team, in order to receive the most appropriate treatment, since
      many cystic liver lesions have a malignant potential and evolution. 

PMID- 24282351
TI  - Branched-chain amino acids in liver diseases.
AB  - Branched chain amino acids (BCAAs) have been shown to affect gene expression,
      protein metabolism, apoptosis and regeneration of hepatocytes, and insulin
      resistance. They have also been shown to inhibit the proliferation of liver
      cancer cells in vitro, and are essential for lymphocyte proliferation and
      dendritic cell maturation. In patients with advanced chronic liver disease, BCAA
      concentrations are low, whereas the concentrations of aromatic amino acids such
      as phenylalanine and tyrosine are high, conditions that may be closely associated
      with hepatic encephalopathy and the prognosis of these patients. Based on these
      basic observations, patients with advanced chronic liver disease have been
      treated clinically with BCAA-rich medicines, with positive effects. 

PMID- 24282352
TI  - Liver diseases in pregnancy: diseases not unique to pregnancy.
AB  - Pregnancy is a special clinical state with several normal physiological changes
      that influence body organs including the liver. Liver disease can cause
      significant morbidity and mortality in both pregnant women and their infants. Few
      challenges arise in reaching an accurate diagnosis in light of such physiological
      changes. Laboratory test results should be carefully interpreted and the
      knowledge of what normal changes to expect is prudent to avoid clinical
      misjudgment. Other challenges entail the methods of treatment and their safety
      for both the mother and the baby. This review summarizes liver diseases that are
      not unique to pregnancy. We focus on viral hepatitis and its mode of
      transmission, diagnosis, effect on the pregnancy, the mother, the infant,
      treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis,
      primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein
      thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with
      cirrhosis because of the metabolic and hormonal changes associated with
      cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women.
      Management of portal hypertension during pregnancy is discussed. Pregnancy
      increases the pathogenicity leading to an increase in the rate of gallstones. We
      discuss some of the interventions for gallstones in pregnancy if symptoms arise.
      Finally, we provide an overview of some of the options in managing hepatic
      adenomas and hepatocellular carcinoma during pregnancy. 

PMID- 24282353
TI  - Liver diseases in pregnancy: diseases unique to pregnancy.
AB  - Pregnancy is a special clinical state with several normal physiological changes
      that influence body organs including the liver. Liver disease can cause
      significant morbidity and mortality in both pregnant women and their infants.
      This review summarizes liver diseases that are unique to pregnancy. We discuss
      clinical conditions that are seen only in pregnant women and involve the liver;
      from Hyperemesis Gravidarum that happens in 1 out of 200 pregnancies and
      Intrahepatic Cholestasis of Pregnancy (0.5%-1.5% prevalence), to the more
      frequent condition of preeclampsia (10% prevalence) and its severe form;
      hemolysis, elevated liver enzymes, and a low platelet count syndrome (12% of
      pregnancies with preeclampsia), to the rare entity of Acute Fatty Liver of
      Pregnancy (incidence of 1 per 7270 to 13000 deliveries). Although pathogeneses
      behind the development of these aliments are not fully understood, theories have
      been proposed. Some propose the special physiological changes that accompany
      pregnancy as a precipitant. Others suggest a constellation of factors including
      both the mother and her fetus that come together to trigger those unique
      conditions. Reaching a timely and accurate diagnosis of such conditions can be
      challenging. The timing of the condition in relation toward which trimester it
      starts at is a key. Accurate diagnosis can be made using specific clinical
      findings and blood tests. Some entities have well-defined criteria that help not
      only in making the diagnosis, but also in classifying the disease according to
      its severity. Management of these conditions range from simple medical remedies
      to measures such as immediate termination of the pregnancy. In specific
      conditions, it is prudent to have expert obstetric and medical specialists
      teaming up to help improve the outcomes. 

PMID- 24282354
TI  - Liver diseases in pregnancy: liver transplantation in pregnancy.
AB  - Pregnancy in patients with advanced liver disease is uncommon as most women with
      decompensated cirrhosis are infertile and have high rate of anovulation. However,
      if gestation ensued; it is very challenging and carries high risks for both the
      mother and the baby such as higher rates of spontaneous abortion, prematurity,
      pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage,
      and a potential for life-threatening variceal hemorrhage and hepatic
      decompensation. In contrary, with orthotopic liver transplantation, menstruation
      resumes and most women of childbearing age are able to conceive, give birth and
      lead a better quality of life. Women with orthotopic liver transplantation
      seeking pregnancy should be managed carefully by a team consultation with
      transplant hepatologist, maternal-fetal medicine specialist and other
      specialists. Pregnant liver transplant recipients need to stay on
      immunosuppression medication to prevent allograft rejection. Furthermore, these
      medications need to be monitored carefully and continued throughout pregnancy to
      avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to
      2 years after transplantation minimizes fetal exposure to high doses of
      immunosuppressants. Pregnant female liver transplant patients have a high rate of
      cesarean delivery likely due to the high rate of prematurity in this population.
      Recent reports suggest that with close monitoring and multidisciplinary team
      approach, most female liver transplant recipient of childbearing age will lead a
      successful pregnancy. 

PMID- 24282355
TI  - Use of exclusive enteral nutrition in adults with Crohn's disease: a review.
AB  - Exclusive enteral nutrition (EEN) is well-established as a first line therapy
      instead of corticosteroid (CS) therapy to treat active Crohn's disease (CD) in
      children. It also has been shown to have benefits over and above induction of
      disease remission in paediatric populations. However, other than in Japanese
      populations, this intervention is not routinely utilised in adults. To
      investigate potential reasons for variation in response between adult studies of
      EEN and CS therapy. The Ovid database was searched over a 6-mo period. Articles
      directly comparing EEN and CS therapy in adults were included. Eleven articles
      were identified. EEN therapy remission rates varied considerably. Poor compliance
      with EEN therapy due to unpalatable formula was an issue in half of the studies.
      Remission rates of studies that only included patients with previously
      untreated/new CD were higher than studies including patients with both existing
      and new disease. There was limited evidence to determine if disease location,
      duration of disease or age of diagnosis affected EEN therapy outcomes. There is
      some evidence to support the use of EEN as a treatment option for a select group
      of adults, namely those motivated to adhere to an EEN regimen and possibly those
      newly diagnosed with CD. In addition, the use of more palatable formulas could
      improve treatment compliance. 

PMID- 24282356
TI  - Diagnosis of IgG4-related sclerosing cholangitis.
AB  - IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune
      pancreatitis. However, the diffuse cholangiographic abnormalities observed in
      IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and
      the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC
      responds well to steroid therapy, whereas PSC is only effectively treated with
      liver transplantation and CC requires surgical intervention. Since IgG4-SC was
      first described, it has become a third distinct clinical entity of sclerosing
      cholangitis. The aim of this review was to introduce the diagnostic methods for
      IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of
      characteristic clinical, serological, morphological, and histopathological
      features after cholangiographic classification and targeting of a disease for
      differential diagnosis. When intrapancreatic stenosis is detected, pancreatic
      cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident,
      PSC should be distinguished on the basis of cholangiographic findings and liver
      biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is
      suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC
      should be discriminated by ultrasonography, intraductal ultrasonography, bile
      duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL. 

PMID- 24282357
TI  - Laparoscopy-assisted percutaneous endoscopic gastrostomy enables enteral
      nutrition even in patients with distorted anatomy.
AB  - AIM: To analyzed whether laparoscopy-assisted percutaneous endoscopic gastrostomy
      (PEG) could be a valuable option for patients with complicated anatomy. METHODS:
      A retrospective analysis of twelve patients (seven females, five males; six
      children, six young adults; mean age 19.2 years) with cerebral palsy, spastic
      quadriparesis, severe kyphoscoliosis and interposed organs and who required
      enteral nutrition (EN) due to starvation was performed. For all patients,
      standard PEG placement was impossible due to distorted anatomy. All the patients
      qualified for the laparoscopy-assisted PEG procedure. RESULTS: In all twelve
      patients, the laparoscopy-assisted PEG was successful, and EN was introduced four
      to six hours after the PEG placement. There were no complications in the
      perioperative period, either technical or metabolic. All the patients were
      discharged from the hospital and were then effectively fed using bolus methods.
      CONCLUSION: Laparoscopy-assisted PEG should become the method of choice for
      gastrostomy tube placement and subsequent EN if PEG placement cannot be performed
      safely.

PMID- 24282358
TI  - Is early limited surgery associated with a more benign disease course in Crohn's
      disease?
AB  - AIM: To analyze the difference in disease course and need for surgery in patients
      with Crohn's disease (CD). METHODS: Data of 506 patients with incident CD were
      analyzed (age at diagnosis: 31.5 +/- 13.8 years). Both hospital and outpatient
      records were collected prospectively with a complete clinical follow-up and
      comprehensively reviewed in the population-based Veszprem province database,
      which includes incident CD patients diagnosed between January 1, 1977 and
      December 31, 2008. Follow-up data were collected until December 31, 2009. All
      patients included had at least 1 year of follow-up available. Patients with
      indeterminate colitis at diagnosis were excluded from the analysis. RESULTS:
      Overall, 73 patients (14.4%) required resective surgery within 1 year of
      diagnosis. Steroid exposure and need for biological therapy were lower in
      patients with early limited surgery (P < 0.001 and P = 0.09). In addition,
      surgery rates during follow-up in patients with and without early surgery
      differed significantly after matching on propensity scores (P < 0.001, HR =
      0.23). The need for reoperation was also lower in patients with early limited
      resective surgery (P = 0.038, HR = 0.42) in a Kaplan-Meier and multivariate Cox
      regression (P = 0.04) analysis. However, this advantage was not observed after
      matching on propensity scores (P(Logrank) = 0.656, P(Breslow) = 0.498).
      CONCLUSION: Long-term surgery rates and overall exposure to steroids and
      biological agents were lower in patients with early limited resective surgery,
      but reoperation rates did not differ.

PMID- 24282359
TI  - Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: an
      Egyptian study.
AB  - AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs)
      in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS:
      Three subject groups were included in the study: group 1 involved 50 control
      subjects, group 2 involved 50 patients with chronic HCV infection and group 3
      involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as
      co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in
      peripheral blood mononuclear cells by real-time polymerase chain reaction.
      Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All
      findings were correlated with disease activity, viral load and fibrogenesis.
      RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86
      and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were
      significantly higher in group 3 vs group 2. There was a significant elevation in
      PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in
      group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in
      groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs
      group 2. HA level was significantly correlated with disease activity and fibrosis
      grade in group 2. IL-10 was significantly correlated with fibrosis grade in group
      2. There were significant negative correlations between co-stimulatory markers
      and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a
      significant positive correlation between PD-L1 and viral load in both HCV groups.
      CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant
      increase in a DC co-inhibitory marker were observed in HCV subjects and to a
      lesser extent in dialysis patients.

PMID- 24282360
TI  - Characteristics of nonvariceal upper gastrointestinal hemorrhage in patients with
      chronic kidney disease.
AB  - AIM: To evaluate the clinical characteristics of nonvariceal upper
      gastrointestinal hemorrhage (NGIH) in patients with chronic kidney disease (CKD).
      METHODS: From 2003 to 2010, a total of 72 CKD patients (male n = 52, 72.2%;
      female n = 20, 27.8%) who had undergone endoscopic treatments for NGIH were
      retrospectively identified. Clinical findings, endoscopic features, prognosis,
      rebleeding risk factors, and mortality-related factors were evaluated. The
      characteristics of the patients and rebleeding-related data were recorded for the
      following variables: gender, age, alcohol use and smoking history, past
      hemorrhage history, endoscopic findings (the cause, location, and size of the
      hemorrhage and the hemorrhagic state), therapeutic options for endoscopy,
      endoscopist experience, clinical outcomes, and mortality. RESULTS: The average
      size of the hemorrhagic site was 13.7 +/- 10.2 mm, and the most common
      hemorrhagic site in the stomach was the antrum (n = 21, 43.8%). The most frequent
      method of hemostasis was combination therapy (n = 32, 44.4%). The incidence of
      rebleeding was 37.5% (n = 27), and 16.7% (n = 12) of patients expired due to
      hemorrhage. In a multivariate analysis of the risk factors for rebleeding,
      alcoholism (OR = 11.19, P = 0.02), the experience of endoscopists (OR = 0.56, P =
      0.03), and combination endoscopic therapy (OR = 0.06, P = 0.01) compared with
      monotherapy were significantly related to rebleeding after endoscopic therapy. In
      a risk analysis of mortality after endoscopic therapy, only rebleeding was
      related to mortality (OR = 7.1, P = 0.02). CONCLUSION: Intensive combined
      endoscopic treatments by experienced endoscopists are necessary for the treatment
      of NGIH in patients with CKD, especially when a patient is an alcoholic.

PMID- 24282361
TI  - Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer
      cells.
AB  - AIM: To investigate the events associated with the apoptotic effect of p-Coumaric
      acid, one of the phenolic components of honey, in human colorectal carcinoma (HCT
      15) cells. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium-bromide
      assay was performed to determine the antiproliferative effect of p-Coumaric acid
      against colon cancer cells. Colony forming assay was conducted to quantify the
      colony inhibition in HCT 15 and HT 29 colon cancer cells after p-Coumaric acid
      treatment. Propidium Iodide staining of the HCT 15 cells using flow cytometry was
      done to study the changes in the cell cycle of treated cells. Identification of
      apoptosis was done using scanning electron microscope and photomicrograph
      evaluation of HCT 15 cells after exposing to p-Coumaric acid. Levels of reactive
      oxygen species (ROS) of HCT 15 cells exposed to p-Coumaric acid was evaluated
      using 2', 7'-dichlorfluorescein-diacetate. Mitochondrial membrane potential of
      HCT-15 was assessed using rhodamine-123 with the help of flow cytometry. Lipid
      layer breaks associated with p-Coumaric acid treatment was quantified using the
      dye merocyanine 540. Apoptosis was confirmed and quantified using flow cytometric
      analysis of HCT 15 cells subjected to p-Coumaric acid treatment after staining
      with YO-PRO-1. RESULTS: Antiproliferative test showed p-Coumaric acid has an
      inhibitory effect on HCT 15 and HT 29 cells with an IC50 (concentration for 50%
      inhibition) value of 1400 and 1600 MUmol/L respectively. Colony forming assay
      revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p
      Coumaric acid treatment. Propidium iodide staining of treated HCT 15 cells showed
      increasing accumulation of apoptotic cells (37.45 +/- 1.98 vs 1.07 +/- 1.01) at
      sub-G1 phase of the cell cycle after p-Coumaric acid treatment. HCT-15 cells
      observed with photomicrograph and scanning electron microscope showed the signs
      of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure.
      Evaluation of the lipid layer showed increasing lipid layer breaks was associated
      with the growth inhibition of p-Coumaric acid. A fall in mitochondrial membrane
      potential and increasing ROS generation was observed in the p-Coumaric acid
      treated cells. Further apoptosis evaluated by YO-PRO-1 staining also showed the
      time-dependent increase of apoptotic cells after treatment. CONCLUSION: These
      results depicted that p-Coumaric acid inhibited the growth of colon cancer cells
      by inducing apoptosis through ROS-mitochondrial pathway.

PMID- 24282362
TI  - Screening of SLC25A13 mutation in the Thai population.
AB  - AIM: To determine the prevalence of SLC25A13 mutations in the Thai population.
      METHODS: A total of 1537 subjects representing the Thai population were screened
      for a novel pathologic allele p.Met1? (c.2T > C) and six previously known common
      SLC25A13 mutations: [I] (c.851_854delGTAT), [II] (g.IVS11 + 1G > A), [III]
      (c.1638_1660dup), [IV] (p.S225X), [V] (IVS13 + 1G > A), and [XIX] (g.IVS16ins3kb)
      using a newly developed TaqMan and established HybProbe assay, respectively.
      Sanger sequencing was employed for specimens showing an aberrant peak to confirm
      the targeted mutation as well as the unknown aberrant peaks detected. Frequencies
      of the mutations identified were compared in each region. Carrier frequency and
      disease prevalence of citrin deficiency caused by SCL25A13 mutations were
      estimated. RESULTS: p.Met1? was identified in the heterozygous state in 85
      individuals, giving a carrier frequency of 1/18, which suggests possible
      selective advantage of this variant. The question of p.Met1? homozygote lethality
      remains unanswered which may serve as an explanation as to why this homozygote
      has yet to be identified in patients/controls even with high allele frequency.
      The p.Met1? mutation has rarely been studied in populations other than Thai and
      Chinese; therefore, may have been overlooked. Development of the TaqMan assay in
      the present study would allow a simple, rapid, and cost-effective method for mass
      screening. Heterozygous mutations: [XIX] and [I] were identified in 17
      individuals, giving a carrier rate of 1/90 and a calculated homozygote rate of
      1/33000. Two novel variants, g.IVS11 + 17C > G and c.1311C > T, of unknown
      clinical significance were identified at low frequency. CONCLUSION: This study
      highlighted the current underestimation of citrin deficiency and suggests the
      possible selective advantage of the p.Met1? allele.

PMID- 24282363
TI  - Single-incision vs three-incision laparoscopic cholecystectomy for complicated
      and uncomplicated acute cholecystitis.
AB  - AIM: To compare the clinical outcome of single-incision laparoscopic
      cholecystectomy (SILC) and three-incision laparoscopic cholecystectomy (3ILC) for
      acute cholecystitis. METHODS: From July 2009 to September 2012, 136 patients
      underwent SILC or 3ILC for acute cholecystitis at a tertiary referral hospital.
      One experienced surgeon performed every procedure using 5 or 10 mm 30-degree
      laparoscopes, straight instruments, and conventional ports. Five patients with
      perforated gallbladder and diffuse peritonitis and 23 patients with mild acute
      cholecystitis were excluded. The remaining 108 patients were divided into
      complicated and uncomplicated groups according to pathologic findings. Patient
      demography, clinical data, operative results and complications were recorded and
      analyzed. RESULTS: Fifty patients with gangrenous cholecystitis, gallbladder
      empyema, or hydrops were classified as the complicated group, and 58 patients
      with acute cholecystitis were classified as the uncomplicated group. Twenty-three
      (46.0%) of the patients in the complicated group (n = 50) and 39 (67.2%) of the
      patients in the uncomplicated group (n = 58) underwent SILC; all others underwent
      3ILC. The postoperative length of hospital stay (PLOS) was significantly shorter
      in the SILC subgroups than the 3ILC subgroups (3.5 +/- 1.1 d vs 4.6 +/- 1.3 d, P
      < 0.01 in the complicated group; 2.9 +/- 1.1 d vs 3.7 +/- 1.4 d, P < 0.05 in the
      uncomplicated group). The maximum body temperature recorded at day 1 and at day 2
      following the procedure was lower in the SILC subgroups, but the difference
      reached statistical significance only in the uncomplicated group (37.41 +/- 0.56 
      degrees C vs 37.80 +/- 0.72  degrees C, P < 0.05 on postoperative day 1; 37.10 +/
      0.43  degrees C vs 37.57 +/- 0.54  degrees C, P < 0.01 on postoperative day 2).
      The operative time, estimated blood loss, postoperative narcotic use, total
      length of hospital stay, conversion rates, and complication rates were similar in
      both SILC and 3ILC subgroups. The complicated group had longer operative time
      (122.2 +/- 35.0 min vs 106.6 +/- 43.6 min, P < 0.05), longer PLOS (4.1 +/- 1.3 d
      vs 3.2 +/- 1.2 d, P < 0.001), and higher conversion rates (36.0% vs 19.0%, P <
      0.05) compared with the uncomplicated group. CONCLUSION: SILC is safe and
      efficacious for patients with acute cholecystitis. The main benefit is a faster
      recovery than that achieved with 3ILC.

PMID- 24282364
TI  - Transanal natural orifice specimen extraction for laparoscopic anterior resection
      in rectal cancer.
AB  - AIM: To investigate whether transanal natural orifice specimen extraction (NOSE)
      is a better technique for rectal cancer resection. METHODS: A prospectively
      designed database of a consecutive series of patients undergoing laparoscopic low
      anterior resection for rectal cancer with various tumor-node-metastasis
      classifications from March 2011 to February 2012 at the First Affiliated Hospital
      of Sun Yat-Sen University was analyzed. Patient selection for transanal specimen
      extraction and intracorporeal anastomosis was made on the basis of tumor size and
      distance of rectal lesions from the anal verge. Demographic data, operative
      parameters, and postoperative outcomes were assessed. RESULTS: None of the
      patients was converted to laparotomy. Respectively, there were 16 cases in the
      low anastomosis and five in the ultralow anastomosis groups. Mean age of the
      patients was 45.4 years, and mean body mass index was 23.1 kg/m2. Mean distance
      of the lower edge of the lesion from the anal verge was 8.3 cm. Mean operating
      time was 132 min, and mean intraoperative blood loss was 84 mL. According to the
      principle of rectal cancer surgery, we performed D2 lymph node dissection in 13
      cases and D3 in eight. Mean lymph nodes harvest was 17.8, and the number of
      positive lymph nodes was 3.4. Median hospital stay was 6.7 d. No serious
      postoperative complication occurred except for one anastomotic leakage. All
      patients remained disease free. Mean Wexner score was 3.7 at 11 mo after the
      operation. CONCLUSION: Transanal NOSE for total laparoscopic low/ultralow
      anterior resection is feasible, safe and oncologically sound. Further studies
      with long-term outcomes are needed to explore its potential advantages.

PMID- 24282365
TI  - PU.1-silenced dendritic cells prolong allograft survival in rats receiving
      intestinal transplantation.
AB  - AIM: To investigate the function of PU.1-silenced semi-mature dendritic cells
      (DCs) and the possibility of utilizing cell immunity in rat intestinal
      transplantation. METHODS: DCs were isolated from the bone marrow of F344 rats and
      cultured using the adherent method. The PU.1 gene was knocked down in DCs using
      small interfering RNAs (siRNAs) for 24 h, and the cells were then incubated with
      lipopolysaccharide for 48 h. The PU.1 siRNA that had the highest silencing
      efficiency was screened using reverse transcription-polymerase chain reaction and
      Western blot for further study. The tolerance capacity was analyzed and compared
      between PU.1-silenced DCs (siRNA PU.1 group), negative control-silenced DCs
      (siRNA NC group) and immature DCs (control group) both in vitro and in vivo.
      RESULTS: Blocking expression of the PU.1 gene in vitro led to a reduction in DC
      maturation and an increased tolerance capability. PU.1-silenced DCs expressed
      moderate levels of major histocompatibility complex (MHC)-II and low levels of co
      stimulatory molecules, and produced more interleukin (IL)-10, but less IL-12.
      Compared with the negative control group, surface molecules cluster of
      differentiation 80 (CD80), CD86 and MHC-II in the siRNA PU.1 group were 27.0% +/-
      5.6%, 23.6% +/- 4.8% and 36.8% +/- 6.8%, respectively, and showed a significantly
      lower trend (P < 0.05). In vivo treatment of recipients with PU.1-silenced DCs
      injected before intestinal transplantation (siRNA PU.1 group), significantly
      prolonged allograft survival and resulted in better tissue histopathology
      compared with the siRNA NC group and control group. Mean survival time after
      transplantation was 14.3 +/- 3.3 d in the siRNA PU.1 group (P < 0.05).
      CONCLUSION: PU.1-silenced semi-mature DCs induced partial immune tolerance both
      in vitro and in vivo, which could be used as a new strategy to promote
      transplantation tolerance.

PMID- 24282366
TI  - Biliary casts after liver transplantation: morphology and biochemical analysis.
AB  - AIM: To investigate the pathogenesis of biliary casts after liver transplantation
      relative to their morphology and biochemical markers. METHODS: The microstructure
      of biliary casts was assessed using scanning electron microscopy and Hematoxylin
      and eosin staining assessed their histology. The expression levels of CD3, CD5,
      CD34, CD68 and CD79a in these biliary casts were evaluated immunohistochemically.
      RESULTS: Biliary casts differed widely in their microstructure, with some
      containing blood vessels positive for CD34 and collagen fibers with positive
      Masson staining. Large numbers of neutrophils and other inflammatory cells were
      present, but only on the edge of the biliary casts; although the boundaries were
      clear without crossover. None of the biliary casts contained T-lymphocytes, B
      lymphocytes, macrophages and other inflammatory cells. CONCLUSION: The
      microcostructure of biliary casts differed. Bacteria and acute rejection are not
      clearly related to their formation.

PMID- 24282367
TI  - Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic
      metastasis in colorectal cancer.
AB  - AIM: To investigate the expression of insulin-like growth factor-1 (IGF
      1)/insulin-like growth factor-1 receptor (IGF-1R) in colorectal cancer (CRC)
      tissues and to analyze their correlation with lymphangiogenesis and lymphatic
      metastasis. METHODS: Immunohistochemistry was used to evaluate IGF-1 and IGF-1R
      expression and lymphatic vessel density (LVD) in 40 CRC specimens. The
      correlation between IGF-1/IGF-1R and LVD was investigated. Effects of IGF-1 on
      migration and invasion of CRC cells were examined using transwell chamber assays.
      A LoVo cell xenograft model was established to further detect the role of IGF-1
      in CRC lymphangiogenesis in vivo. RESULTS: Elevated IGF-1 and IGF-1R expression
      in CRC tissues was correlated with lymph node metastasis (r = 0.715 and 0.569,
      respectively, P < 0.05) and tumor TNM stage (r = 0.731 and 0.609, P < 0.05). A
      higher LVD was also found in CRC tissues and was correlated with lymphatic
      metastasis (r = 0.405, P < 0.05). A positive correlation was found between LVD
      and IGF-1R expression (r = 0.437, P < 0.05). Transwell assays revealed that IGF-1
      increased the migration and invasion of CRC cells. In vivo mouse studies showed
      that IGF-1 also increased LVD in LoVo cell xenografts. CONCLUSION: IGF-1/IGF-1R
      signaling induces tumor-associated lymphangiogenesis and contributes to lymphatic
      metastasis of CRC.

PMID- 24282369
TI  - Is Dor fundoplication optimum after laparoscopic Heller myotomy for achalasia? A
      meta-analysis.
AB  - AIM: To compare the outcome of acid reflux prevention by Dor fundoplication after
      laparoscopic Heller myotomy (LHM) for achalasia. METHODS: Electronic database
      PubMed, Ovid (Evidence-Based Medicine Reviews, EmBase and Ovid MEDLINE) and
      Cochrane Library were searched between January 1995 and September 2012.
      Bibliographic citation management software (EndNote X3) was used for extracted
      literature management. Quality assessment of random controlled studies (RCTs) and
      non-RCTs was performed according to the Cochrane Handbook for Systematic Reviews
      of Interventions 5.1.0 and a modification of the Newcastle-Ottawa Scale,
      respectively. The data were analyzed using Review Manager (Version 5.1), and
      sensitivity analysis was performed by sequentially omitting each study. RESULTS:
      Finally, 6 studies, including a total of 523 achalasia patients, compared Dor
      fundoplication with other types of fundoplication after LHM (Dor-other group),
      and 8 studies, including a total of 528 achalasia patients, compared Dor
      fundoplication with no fundoplication after LHM (Dor-no group). Dor
      fundoplication was associated with a significantly higher recurrence rate of
      clinical regurgitation and pathological acid reflux compared with the other
      fundoplication group (OR = 7.16, 95%CI: 1.25-40.93, P = 0.03, and OR = 3.79,
      95%CI: 1.23-11.72, P = 0.02, respectively). In addition, there were no
      significant differences between Dor fundoplication and no fundoplication in all
      subjects. Other outcomes, including complications, dysphagia, postoperative
      physiologic testing, and operation-related data displayed no significant
      differences in the two comparison groups. CONCLUSION: Dor fundoplication is not
      the optimum procedure after LHM for achalasia. We suggest more attention should
      be paid on quality of life among different fundoplications.

PMID- 24282368
TI  - Identification of Annexin A1 protein expression in human gastric adenocarcinoma
      using proteomics and tissue microarray.
AB  - AIM: To study the differential expression of Annexin A1 (ANXA1) protein in human
      gastric adenocarcinoma. This study was also designed to analyze the relationship
      between ANXA1 expression and the clinicopathological parameters of gastric
      carcinoma. METHODS: Purified gastric adenocarcinoma cells (GAC) and normal
      gastric epithelial cells (NGEC) were obtained from 15 patients with gastric
      cancer by laser capture microdissection. All of the peptide specimens were
      labeled as 18O/16O after trypsin digestion. Differential protein expressions were
      quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid
      chromatography-mass/mass spectrometry (nano-RPLC-MS/MS). The expressions of ANXA1
      in GAC and NGEC were verified by western blot analysis. The tissue microarray
      containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma
      specimens was detected by immunohistochemistry (IHC). The relationship between
      ANXA1 expression and clinicopathological parametes of gastric carcinoma was
      analyzed. RESULTS: A total of 78 differential proteins were identified. Western
      blotting revealed that ANXA1 expression was significantly upregulated in GAC
      (2.17/1, P < 0.01). IHC results showed the correlations between ANXA1 protein
      expression and the clinicopathological parameters, including invasive depth (T
      stage), lymph node metastasis (N stage), distant metastasis (M stage) and tumour
      lymph node metastasis stage (P < 0.01). However, the correlations between ANXA1
      protein expression and the remaining clinicopathological parameters, including
      sex, age, histological differentiation and the size of tumour were not found (P >
      0.05). CONCLUSION: The upregulated ANXA1 expression may be associated with
      carcinogenesis, progression, invasion and metastasis of GAC. This protein could
      be considered as a biomarker of clinical prognostic prediction and targeted
      therapy of GAC.

PMID- 24282370
TI  - Mesenteric vein thrombosis in a patient heterozygous for factor V Leiden and
      G20210A prothrombin genotypes.
AB  - Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel
      ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia.
      The proportion of patients with primary (or idiopathic) MVT varies from 0% to
      49%, with a decrease in frequency secondary to more recent availability of newer
      investigations for hypercoagulability. The presence of factor V Leiden (FVL) and
      prothrombin G20210A mutations (PGM) have been well documented in these cases.
      However, there have been scarce case reports describing MVT in heterozygotes of
      both these mutations occurring simultaneously and its implications on long term
      management. Our case describes acute MVT in a previously asymptomatic young
      patient with no prior history of venous thromboembolism. The patient was found to
      be heterozygous for FVL and PGM and treated with lifelong anticoagulation with
      warfarin (goal international normalized ratio: 2-3) and avoidance of hormonal
      contraceptives. 

PMID- 24282371
TI  - Development of enterohepatic fistula after embolization in ileal gastrointestinal
      stromal tumor: a case report.
AB  - Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor of the
      gastrointestinal tract that has been associated with the formation of fistulas to
      adjacent organs in few case reports. However, GIST with enterohepatic fistula has
      not been reported. Here we report the case of an enterohepatic fistula that
      occurred after embolization of a liver mass originating in the distal ileum. An
      87-year-old woman was hospitalized for melena. On initial conventional endoscopy,
      a bleeding focus in the gastrointestinal tract was not found. Because of massive
      hematochezia, enteroscopy was performed through the anus. A protruding,
      ulcerative mass was found in the distal ileum that was suspected to be the source
      of the bleeding; a biopsy sample was taken. Electrocoagulation was not successful
      in controlling the bleeding; therefore, embolization was performed. After
      embolization, the patient developed a high fever and severe abdominal tenderness
      with rebound tenderness. Follow-up abdominopelvic computed tomography revealed an
      enterohepatic fistula between the liver and distal ileum. The fistula was treated
      surgically by segmental resection of the distal ileum and unlooping of the liver
      mass. 

PMID- 24282373
TI  - Peroral endoscopic myotomy for the treatment of achalasia: an analysis.
AB  - Achalasia is a motility disorder of the esophagus, characterized by aperistalsis
      of the esophageal body and incomplete relaxation of the lower esophageal
      sphincter (LES). Treatment of achalasia is currently aimed at decreasing the
      resting pressure in the LES. Peroral endoscopic myotomy (POEM) is an emerging
      novel endoscopic procedure for the treatment of achalasia with initial data
      suggesting an acceptable safety profile, excellent short-term symptom resolution,
      low incidence of postprocedural gastroesophageal reflux (GER), and improvement in
      manometric outcomes. Further prospective randomized trials are required to
      evaluate the long-term effectiveness of this promising technique compared to
      other treatment modalities for achalasia. In this review we outline the technical
      aspects of POEM, summarize the available data on safety and outcomes, and suggest
      future directions for further advancement of this minimally invasive approach for
      the treatment of achalasia. 

PMID- 24282372
TI  - Unusual early-stage pancreatic sarcomatoid carcinoma.
AB  - Sarcomatoid carcinoma of the pancreas (SCP) is a very rare pathological type of
      carcinoma that usually has a poor prognosis. Its pathogenesis has not been
      elucidated. We herein report a case of an early-stage SCP involving successful
      treatment and a good prognosis. The patient was a 48-year-old Chinese man with a
      5-mo history of vague abdominal pain. Ultrasonography revealed a 93 mm * 94 mm *
      75 mm mass of mixed echogenicity in the tail of the pancreas. Laboratory test
      results were within the normal range, with the exception of an obviously
      increased pretreatment neuron-specific enolase level. The plasma transforming
      growth factor (TGF)beta1 and interleukin-11 levels were obviously increased
      according to enzyme-linked immunosorbent assay. Microscopically, the excised
      tumor tissue comprised cancer cells and mesenchymal cells. Immunohistochemical
      analysis was positive for alpha-1-antichymotrypsin, pan-cytokeratin, cytokeratin
      19, cytokeratin 8/18, and vimentin and negative for CD68 and lysozyme. The
      pathogenetic mechanism of this case shows that TGFbeta1 may regulate the
      epithelial-to-mesenchymal transition in SCP. With early eradication of the tumor
      and systemic therapy, this patient has been alive for more than 3 years without
      tumor recurrence or distant metastasis. This case is also the first to show that
      TGFbeta1 may regulate the epithelial-to-mesenchymal transition in early-stage
      SCP. 

PMID- 24282374
TI  - Rapid screening of novel agents for combination therapy in sarcomas.
AB  - For patients with sarcoma, metastatic disease remains very difficult to cure, and
      outcomes remain less than optimal. Treatment options have not largely changed,
      although some promising gains have been made with single agents in specific
      subtypes with the use of targeted agents. Here, we developed a system to
      investigate synergy of combinations of targeted and cytotoxic agents in a panel
      of sarcoma cell lines. Agents were investigated alone and in combination with
      varying dose ratios. Dose-response curves were analyzed for synergy using methods
      derived from Chou and Talalay (1984). A promising combination, dasatinib and
      triciribine, was explored in a murine model using the A673 cell line, and tumors
      were evaluated by MRI and histology for therapy effect. We found that histone
      deacetylase inhibitors were synergistic with etoposide, dasatinib, and Akt
      inhibitors across cell lines. Sorafenib and topotecan demonstrated a mixed
      response. Our systematic drug screening method allowed us to screen a large
      number of combinations of sarcoma agents. This method can be easily modified to
      accommodate other cell line models, and confirmatory assays, such as animal
      experiments, can provide excellent preclinical data to inform clinical trials for
      these rare malignancies. 

PMID- 24282375
TI  - Maternal and foetal cardiovascular effects of the anaesthetic alfaxalone in 2
      hydroxypropyl-beta-cyclodextrin in the pregnant ewe.
AB  - The objective of this study was to determine the pharmacodynamics effects of the
      anaesthetic alfaxalone in 2-hydroxypropyl- beta -cyclodextrin in pregnant sheep
      after the intravenous injection of a 2 mg/kg weight dose. Six pregnant Ripollesa
      sheep, weighing 47.1 +/- 4.4 kg, were used. Twenty-four hours after
      instrumentation, sheep were anaesthetized with intravenous alfaxalone in
      cyclodextrin. Time to standing from anaesthesia was 30.0 +/- 10.81 min. Foetal
      heart rate increased significantly during the first 5 min after alfaxalone
      administration. Significant differences were observed in maternal diastolic
      arterial blood pressure between minute 10 and minutes 90, 120, 150, 180, 210, and
      240. Significant differences were observed for foetal systolic arterial blood
      pressure between 5 and 30 min after alfaxalone administration. Significant
      differences in foetal pH were detected during the entire study period, whereas
      maternal pH returned to baseline values by 60 min after alfaxalone
      administration. The present study indicated that alfaxalone in 2-hydroxypropyl-
      beta -cyclodextrin administered as an intravenous bolus at 2 mg/kg body weight
      produced minimal adverse effects and an uneventful recovery from anaesthesia in
      pregnant sheep and their foetus.

PMID- 24282376
TI  - The analysis of efficacy and failure factors of uterine artery methotrexate
      infusion and embolization in treatment of cesarean scar pregnancy.
AB  - OBJECTIVES: This study observes therapeutic efficacy of uterine artery
      embolization combined with MTX infusion which terminates cesarean scar pregnancy
      (CSP) and induces three factors which probably relate to failure. METHODS: Twenty
      three CSP patients were treated with combined uterine artery MTX infusion and
      embolization. Among them six patients with severe hemorrhage were immediately
      treated with interventional operation. Clinical effects were estimated by
      symptoms, serum beta-hCG, ultrasound, and MR. RESULTS: Interventional treatments
      were technologically successful in 22 patients except one. Immediate hemostasis
      was achieved in all 6 patients with massive colporrhagia. No occurrence of
      infection and uterine necrosis was observed, but 12 women suffered abdominal
      pains. Nineteen patients' uteri were preserved, whereas four underwent
      hysterectomy eventually. CONCLUSIONS: Transcatheter arterial chemoembolization is
      effective to treat high-risk CSP in preference to hysterectomy. To achieve more
      successful outcomes, three factors should be highlighted: adequate MTX dosage,
      appropriate embolic material, and complete embolization of target arteries that
      supply blood to embryo in the scar.

PMID- 24282377
TI  - Multiple solutions for a singular quasilinear elliptic system.
AB  - We consider the multiplicity of nontrivial solutions of the following quasilinear
      elliptic system -div(|x|(-ap)|?u|(p-2)?u) + f1(x)|u|(p-2) u = (alpha/(alpha +
      beta))g(x)|u| (alpha-2) u|v| (beta) + lambdah1(x)|u| (gamma-2) u + l1(x), 
      div(|x|(-ap) |?v| (p-2)?v) + f2(x)|v| (p-2) v = (beta/(alpha + beta))g(x)|v|(beta
      2) v|u|(alpha) + MUh 2(x)|v|(gamma-2)v + l 2(x), u(x) > 0, v(x) > 0, x ? R(N),
      where lambda, MU > 0, 1 < p < N, 1 < gamma < p < alpha + beta < p* = Np/(N-pd), 0
      <= a < (N - p)/p, a <= b < a + 1, d = a + 1 - b > 0. The functions f1(x), f2(x),
      g(x), h1(x), h2(x), l1(x), and l2(x) satisfy some suitable conditions. We will
      prove that the problem has at least two nontrivial solutions by using Mountain
      Pass Theorem and Ekeland's variational principle.

PMID- 24282378
TI  - Riemannian means on special euclidean group and unipotent matrices group.
AB  - Among the noncompact matrix Lie groups, the special Euclidean group and the
      unipotent matrix group play important roles in both theoretic and applied
      studies. The Riemannian means of a finite set of the given points on the two
      matrix groups are investigated, respectively. Based on the left invariant metric
      on the matrix Lie groups, the geodesic between any two points is gotten. And the
      sum of the geodesic distances is taken as the cost function, whose minimizer is
      the Riemannian mean. Moreover, a Riemannian gradient algorithm for computing the
      Riemannian mean on the special Euclidean group and an iterative formula for that
      on the unipotent matrix group are proposed, respectively. Finally, several
      numerical simulations in the 3-dimensional case are given to illustrate our
      results. 

PMID- 24282379
TI  - Effects of chloroform extract of Dryopteris crassirhizoma on the ultramicroscopic
      structures of Meloidogyne incognita.
AB  - In our early experiments, the chloroform extract of D. crassirhizoma was
      demonstrated to contain the highest concentrations of total phloroglucinols among
      several extract fractions and possessed the most effective nematicidal activity.
      This study aimed to ascertain the ultrastructural changes in M. incognita after
      treatment with a D. crassirhizoma chloroform extract at 1 mg.mL-1 for 24 h. It
      was found that the extract exhibited significant destructive effects on the
      worm's ultrastructure and caused distinctive damage to body surfaces and internal
      structures. These results will contribute to a deeper understanding of the
      nematicidal mechanism of D. crassirhizoma, as well as in the design of efficient
      bionematicides.

PMID- 24282380
TI  - "Follow the leader": a centrality guided clustering and its application to social
      network analysis.
AB  - Within graph theory and network analysis, centrality of a vertex measures the
      relative importance of a vertex within a graph. The centrality plays key role in
      network analysis and has been widely studied using different methods. Inspired by
      the idea of vertex centrality, a novel centrality guided clustering (CGC) is
      proposed in this paper. Different from traditional clustering methods which
      usually choose the initial center of a cluster randomly, the CGC clustering
      algorithm starts from a "LEADER"--a vertex with the highest centrality score--and
      a new "member" is added into the same cluster as the "LEADER" when some criterion
      is satisfied. The CGC algorithm also supports overlapping membership. Experiments
      on three benchmark social network data sets are presented and the results
      indicate that the proposed CGC algorithm works well in social network clustering.

PMID- 24282381
TI  - Propagation and introduction of Arnica montana L. into cultivation: a step to
      reduce the pressure on endangered and high-valued medicinal plant species.
AB  - Arnica montana (L.) is an endangered and endemic medicinal plant species in
      Europe. The pressure on natural sources of this plant is alleviated by a suitable
      use of arnica resources in the European region and introduction into cultivation.
      The objective of this study was to describe the impact of different ways of plant
      propagation and introduction on the growth and reproduction mode of this species.
      During the six consecutive years of the field experiment, the vegetative and
      reproductive traits were monitored, and survival time was assessed. The
      particular ways of arnica plant propagation and introduction determined all the
      intrinsic species traits and plant survival. The values of the characteristics
      studied indicated good acclimatization of the arnica ecotype to the climatic
      conditions of eastern Poland. Practical implications from the data presented here
      include the possibility of using the presented modes of arnica propagation and
      introduction in the short- and long-term perspective of arnica cultivation, which
      can give a possibility of better adjustment of raw material production. 

PMID- 24282382
TI  - Performance evaluation of volumetric water content and relative permittivity
      models.
AB  - In recent years many models have been proposed for measuring soil water content
      (theta) based on the permittivity (epsilon) value. Permittivity is one of the
      properties used to determine theta in measurements using the electromagnetic
      method. This method is widely used due to quite substantial differences in values
      of epsilon for air, soil, and water, as it allows the theta value to be measured
      accurately. The performance of six proposed models with one parameter (i.e.,
      permittivity) and five proposed models with two or more parameters (i.e.,
      permittivity, porosity, and dry bulk density of soil) is discussed and evaluated.
      Secondary data obtained from previous studies are used for comparison to
      calibrate and evaluate the models. The results show that the models with one
      parameter proposed by Roth et al. (1992) and Topp et al. (1980) have the greatest
      R2 data errors, while for the model with two parameters, the model proposed by
      Malicki et al. (1996) agrees very well with the data compared with other models.

PMID- 24282383
TI  - Evaluation of the sustaining effects of Tai Chi Qigong in the sixth month in
      promoting psychosocial health in COPD patients: a single-blind, randomized
      controlled trial.
AB  - OBJECTIVES: To evaluate the sustaining effects of Tai Chi Qigong (TCQ) in
      improving the psychosocial health in chronic obstructive pulmonary disease (COPD)
      patients in the sixth month. BACKGROUND: COPD affects both physical and emotional
      aspects of life. Measures to minimize patients' suffering need to be implemented.
      METHODS: 206 COPD patients were randomly assigned into three groups: TCQ group,
      exercise group, and control group. The TCQ group completed a three-month TCQ
      program, the exercise group practiced breathing and walking exercise, and the
      control group received usual care. RESULTS: Significant group-by-time
      interactions in quality of life (QOL) using St. George's respiratory
      questionnaire (P = 0.002) and the perceived social support from friends using
      multidimensional scale of perceived social support (P = 0.04) were noted.
      Improvements were observed in the TCQ group only. CONCLUSIONS: TCQ has sustaining
      effects in improving psychosocial health; it is also a useful and appropriate
      exercise for COPD patients.

PMID- 24282384
TI  - Resveratrol-loaded polymeric nanoparticles: validation of an HPLC-PDA method to
      determine the drug entrapment and evaluation of its antioxidant activity.
AB  - Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles
      containing resveratrol (RVT) were developed, and their antioxidant activity was
      evaluated. An analytical method using high performance liquid chromatography
      (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT
      determination in nanoparticles. The mobile phase consisted of methanol : water
      (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength
      of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm,
      and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles
      containing RVT were evaluated for their ability to scavenge the radical (2,2
      azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS*+). The
      profile obtained from the PLA nanoparticles containing RVT demonstrated that
      after 24 h, there was almost no increase in antioxidant activity, which was lower
      than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG
      nanoparticles, the radical-scavenging activity of RVT was shown to increase with
      time, and after 48 h, it was similar to that observed with free RVT.

PMID- 24282385
TI  - Structural health monitoring of a reinforced concrete building during the severe
      typhoon Vicente in 2012.
AB  - The goal of this study is to investigate the structural performance of reinforced
      concrete building under the influence of severe typhoon. For this purpose, full
      scale monitoring of a 22-story reinforced concrete building was conducted during
      the entire passage process of a severe typhoon "Vicente." Vicente was the eighth
      tropical storm developed in the Western North Pacific Ocean and the South China
      Sea in 2012. Moreover, it was the strongest and most devastating typhoon that
      struck Macao since 1999. The overall duration of the typhoon affected period that
      lasted more than 70 hours and the typhoon eye region covered Macao for around one
      hour. The wind and structural response measurements were acquired throughout the
      entire typhoon affected period. The wind characteristics were analyzed using the
      measured wind data including the wind speed and wind direction time histories.
      Besides, the structural response measurements of the monitored building were
      utilized for modal identification using the Bayesian spectral density approach.
      Detailed analysis of the field data and the typhoon generated effects on the
      structural performance are discussed. 

PMID- 24282386
TI  - ZnO nanoparticles as an efficient, heterogeneous, reusable, and ecofriendly
      catalyst for four-component one-pot green synthesis of pyranopyrazole derivatives
      in water.
AB  - An extremely efficient catalytic protocol for the synthesis of a series of
      pyranopyrazole derivatives developed in a one-pot four-component approach in the
      presence of ZnO nanoparticles as heterogeneous catalyst using water as a green
      solvent is reported. Greenness of the process is well instituted as water is
      exploited both as reaction media and medium for synthesis of catalyst. The ZnO
      nanoparticles exhibited excellent catalytic activity, and the proposed
      methodology is capable of providing the desired products in good yield (85-90%)
      and short reaction time. After reaction course, ZnO nanoparticles can be recycled
      and reused without any apparent loss of activity which makes this process cost
      effective and hence ecofriendly. All the synthesized compounds have been
      characterized on the basis of elemental analysis, IR, 1H NMR, and 13C NMR
      spectral studies.

PMID- 24282387
TI  - Arteriovenous passage times and visual field progression in normal tension
      glaucoma.
AB  - PURPOSE: Fluorescein angiographic studies revealed prolonged arteriovenous
      passage (AVP) times and increased fluorescein filling defects in normal tension
      glaucoma (NTG) compared to healthy controls. The purpose of this study was to
      correlate baseline AVP and fluorescein filling defects with visual field
      progression in patients with NTG. PATIENTS AND METHODS: Patients with a follow-up
      period of at least 3 years and at least 4 visual field examinations were included
      in this retrospective study. Fluorescein angiography was performed at baseline
      using a confocal scanning laser ophthalmoscope (SLO, Rodenstock Instr.);
      fluorescein filling defects and AVP were measured by digital image analysis and
      dye dilution curves (25 Hz). Visual field progression was evaluated using
      regression analysis of the MD (Humphrey-Zeiss, SITA-24-2, MD progression per year
      (dB/year)). 72 patients with NTG were included, 44 patients in study 1
      (fluorescein filling defects) and 28 patients in study 2 (AVP). RESULTS: In study
      1 (mean follow-up 6.6 +/- 1.9 years, 10 +/- 5 visual field tests), MD progression
      per year (-0.51 +/- 0.59 dB/year) was significantly correlated to the age (P =
      0.04, r = -0.29) but not to fluorescein filling defects, IOP, or MD at baseline.
      In study 2 (mean follow-up 6.6 +/- 2.2 years, 10 +/- 5 visual field tests), MD
      progression per year (-0.45 +/- 0.51 dB/year) was significantly correlated to AVP
      (P = 0.03, r = 0.39) but not to age, IOP, or MD at baseline. CONCLUSION: Longer
      AVP times at baseline are correlated to visual field progression in NTG. Impaired
      retinal blood flow seems to be an important factor for glaucoma progression.

PMID- 24282388
TI  - Geometric nonlinear analysis of self-anchored cable-stayed suspension bridges.
AB  - Geometric nonlinearity of self-anchored cable-stayed suspension bridges is
      studied in this paper. The repercussion of shrinkage and creep of concrete, rise
      to-span ratio, and girder camber on the system is discussed. A self-anchored
      cable-stayed suspension bridge with a main span of 800 m is analyzed with linear
      theory, second-order theory, and nonlinear theory, respectively. In the condition
      of various rise-to-span ratios and girder cambers, the moments and displacements
      of both the girder and the pylon under live load are acquired. Based on the
      results it is derived that the second-order theory can be adopted to analyze a
      self-anchored cable-stayed suspension bridge with a main span of 800 m, and the
      error is less than 6%. The shrinkage and creep of concrete impose a conspicuous
      impact on the structure. And it outmatches suspension bridges for system
      stiffness. As the rise-to-span ratio increases, the axial forces of the main
      cable and the girder decline. The system stiffness rises with the girder camber
      being employed.

PMID- 24282389
TI  - Modeling and performance improvement of the constant power regulator systems in
      variable displacement axial piston pump.
AB  - An irregular performance of a mechanical-type constant power regulator is
      considered. In order to find the cause of an irregular discharge flow at the cut
      off pressure area, modeling and numerical simulations are performed to observe
      dynamic behavior of internal parts of the constant power regulator system for a
      swashplate-type axial piston pump. The commercial numerical simulation software
      AMESim is applied to model the mechanical-type regulator with hydraulic pump and
      simulate the performance of it. The validity of the simulation model of the
      constant power regulator system is verified by comparing simulation results with
      experiments. In order to find the cause of the irregular performance of the
      mechanical-type constant power regulator system, the behavior of main components
      such as the spool, sleeve, and counterbalance piston is investigated using
      computer simulation. The shape modification of the counterbalance piston is
      proposed to improve the undesirable performance of the mechanical-type constant
      power regulator. The performance improvement is verified by computer simulation
      using AMESim software. 

PMID- 24282391
TI  - Chemical effect on wellbore instability of Nahr Umr Shale.
AB  - Wellbore instability is one of the major problems that hamper the drilling speed
      in Halfaya Oilfield. Comprehensive analysis of geological and engineering data
      indicates that Halfaya Oilfield features fractured shale in the Nahr Umr
      Formation. Complex accidents such as wellbore collapse and sticking emerged
      frequently in this formation. Tests and theoretical analysis revealed that
      wellbore instability in the Halfaya Oilfield was influenced by chemical effect of
      fractured shale and the formation water with high ionic concentration. The
      influence of three types of drilling fluids on the rock mechanical properties of
      Nahr Umr Shale is tested, and time-dependent collapse pressure is calculated.
      Finally, we put forward engineering countermeasures for safety drilling in
      Halfaya Oilfield and point out that increasing the ionic concentration and
      improving the sealing capacity of the drilling fluid are the way to keep the
      wellbore stable. 

PMID- 24282390
TI  - Possible role of human herpesvirus 6 as a trigger of autoimmune disease.
AB  - Human herpesvirus 6 (HHV-6) infection is common and has a worldwide distribution.
      Recently, HHV-6A and HHV-6B have been reclassified into two distinct species
      based on different biological features (genetic, antigenic, and cell tropism) and
      disease associations. A role for HHV-6A/B has been proposed in several autoimmune
      disorders (AD), including multiple sclerosis (MS), autoimmune connective tissue
      diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the
      above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B
      induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high
      amounts of normally sequestered cell antigens, through lysis of infected cells.
      Another potential trigger is represented by molecular mimicry, with the synthesis
      of viral proteins that resemble cellular molecules, as a mechanism of immune
      escape. The virus could also induce aberrant expression of histocompatibility
      molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B
      interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A)
      could participate in neuroinflammation in the context of MS by promoting
      inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to
      trigger all the above-mentioned mechanisms, more studies are required to fully
      elucidate the possible role of HHV-6A/B as a trigger of AD. 

PMID- 24282392
TI  - Breaking the ice and forging links: the importance of socializing in research.
AB  - When meeting someone for the first time-whether another PhD student, or the
      Founding Editor-in-chief of PLOS Computational Biology-nothing breaks the ice
      like eating pancakes or having drinks together. A social atmosphere provides a
      relaxed, informal environment where people can connect, share ideas, and form
      collaborations. Being able to build a network and thrive in a social environment
      is crucial to a successful scientific career. This article highlights the
      importance of bringing people together who speak the same scientific language in
      an informal setting. Using examples of events held by Regional Student Groups of
      the ISCB's Student Council, this article shows that socializing is much more than
      simply sharing a drink. 

PMID- 24282393
TI  - Parallel evolution of chordate cis-regulatory code for development.
AB  - Urochordates are the closest relatives of vertebrates and at the larval stage,
      possess a characteristic bilateral chordate body plan. In vertebrates, the genes
      that orchestrate embryonic patterning are in part regulated by highly conserved
      non-coding elements (CNEs), yet these elements have not been identified in
      urochordate genomes. Consequently the evolution of the cis-regulatory code for
      urochordate development remains largely uncharacterised. Here, we use genome-wide
      comparisons between C. intestinalis and C. savignyi to identify putative
      urochordate cis-regulatory sequences. Ciona conserved non-coding elements
      (ciCNEs) are associated with largely the same key regulatory genes as vertebrate
      CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene
      expression in both zebrafish and Ciona embryos, in a pattern that at least
      partially overlaps that of the gene they associate with, despite the absence of
      sequence identity. We also show that the ability of a ciCNE to up-regulate gene
      expression in vertebrate embryos can in some cases be localised to short sub
      sequences, suggesting that functional cross-talk may be defined by small regions
      of ancestral regulatory logic, although functional sub-sequences may also be
      dispersed across the whole element. We conclude that the structure and
      organisation of cis-regulatory modules is very different between vertebrates and
      urochordates, reflecting their separate evolutionary histories. However,
      functional cross-talk still exists because the same repertoire of transcription
      factors has likely guided their parallel evolution, exploiting similar sets of
      binding sites but in different combinations. 

PMID- 24282394
TI  - MicroRNAs in the pathophysiology and treatment of status epilepticus.
AB  - MicroRNA (miRNA) are an important class of non-coding RNA which function as post
      transcriptional regulators of gene expression in cells, repressing and fine
      tuning protein output. Prolonged seizures (status epilepticus, SE) can cause
      damage to brain regions such as the hippocampus and result in cognitive deficits
      and the pathogenesis of epilepsy. Emerging work in animal models has found that
      SE produces select changes to miRNAs within the brain. Similar changes in over 20
      miRNAs have been found in the hippocampus in two or more studies, suggesting
      conserved miRNA responses after SE. The miRNA changes that accompany SE are
      predicted to impact levels of multiple proteins involved in neuronal morphology
      and function, gliosis, neuroinflammation, and cell death. miRNA expression also
      displays select changes in the blood after SE, supporting blood genomic profiling
      as potential molecular biomarkers of seizure-damage or epileptogenesis.
      Intracerebral delivery of chemically modified antisense oligonucleotides
      (antagomirs) has been shown to have potent, specific and long-lasting effects on
      brain levels of miRNAs. Targeting miR-34a, miR-132 and miR-184 has been reported
      to alter seizure-induced neuronal death, whereas targeting miR-134 was
      neuroprotective, reduced seizure severity during status epilepticus and reduced
      the later emergence of recurrent spontaneous seizures. These studies support
      roles for miRNAs in the pathophysiology of status epilepticus and miRNAs may
      represent novel therapeutic targets to reduce brain injury and epileptogenesis. 

PMID- 24282396
TI  - Attention and P300-based BCI performance in people with amyotrophic lateral
      sclerosis.
AB  - The purpose of this study was to investigate the support of attentional and
      memory processes in controlling a P300-based brain-computer interface (BCI) in
      people with amyotrophic lateral sclerosis (ALS). Eight people with ALS performed
      two behavioral tasks: (i) a rapid serial visual presentation (RSVP) task,
      screening the temporal filtering capacity and the speed of the update of the
      attentive filter, and (ii) a change detection task, screening the memory capacity
      and the spatial filtering capacity. The participants were also asked to perform a
      P300-based BCI spelling task. By using correlation and regression analyses, we
      found that only the temporal filtering capacity in the RSVP task was a predictor
      of both the P300-based BCI accuracy and of the amplitude of the P300 elicited
      performing the BCI task. We concluded that the ability to keep the attentional
      filter active during the selection of a target influences performance in BCI
      control. 

PMID- 24282395
TI  - Emerging neurotrophic role of GABAB receptors in neuronal circuit development.
AB  - The proper development of highly organized structures in the central nervous
      system is a complex process during which key events - neurogenesis, migration,
      growth, differentiation, and synaptogenesis - have to take place in an
      appropriate manner to create functional neuronal networks. It is now well
      established that GABA, the main inhibitory neurotransmitter in the adult
      mammalian brain, plays more than a classical inhibitory role and can function as
      an important developmental signal early in life. GABA binds to chloride-permeable
      ionotropic GABAA receptors and to G-protein-coupled GABAB receptors (GABAB-Rs).
      Although most of the trophic actions of GABA have been attributed to the
      activation of GABAA receptors, recent advances show that GABAB-Rs also regulate
      fundamental steps of network development. This review summarizes some of the
      recent progress about the neurotrophic role of GABAB-Rs to neuronal development. 

PMID- 24282397
TI  - The default modes of reading: modulation of posterior cingulate and medial
      prefrontal cortex connectivity associated with comprehension and task focus while
      reading.
AB  - Reading is a fundamental human capacity and yet it can easily be derailed by the
      simple act of mind-wandering. A large-scale brain network, referred to as the
      default mode network (DMN), has been shown to be involved in both mind-wandering
      and reading, raising the question as to how the same neural system could be
      implicated in processes with both costs and benefits to narrative comprehension.
      Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore
      whether the intrinsic functional connectivity of the two key midline hubs of the
      DMN-the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex
      (aMPFC)-was predictive of individual differences in reading comprehension and
      task focus recorded outside of the scanner. Worse comprehension was associated
      with greater functional connectivity between the PCC and a region of the ventral
      striatum. Better comprehension was associated with greater functional
      connectivity with a region of the right insula. By contrast reports of increasing
      task focus were associated with functional connectivity from the aMPFC to
      clusters in the PCC, the left parietal and temporal cortex, and the cerebellum.
      Our results suggest that the DMN has both costs (such as poor comprehension) and
      benefits to reading (such as an on-task focus) because its midline core can
      couple its activity with other regions to form distinct functional communities
      that allow seemingly opposing mental states to occur. This flexible coupling
      allows the DMN to participate in cognitive states that complement the act of
      reading as well as others that do not. 

PMID- 24282398
TI  - Paired-pulse transcranial magnetic stimulation reveals probability-dependent
      changes in functional connectivity between right inferior frontal cortex and
      primary motor cortex during go/no-go performance.
AB  - The functional role of the right inferior frontal cortex (rIFC) in mediating
      human behavior is the subject of ongoing debate. Activation of the rIFC has been
      associated with both response inhibition and with signaling action adaptation
      demands resulting from unpredicted events. The goal of this study is to
      investigate the role of rIFC by combining a go/no-go paradigm with paired-pulse
      transcranial magnetic stimulation (ppTMS) over rIFC and the primary motor cortex
      (M1) to probe the functional connectivity between these brain areas. Participants
      performed a go/no-go task with 20% or 80% of the trials requiring response
      inhibition (no-go trials) in a classic and a reversed version of the task,
      respectively. Responses were slower to infrequent compared to frequent go trials,
      while commission errors were more prevalent to infrequent compared to frequent no
      go trials. We hypothesized that if rIFC is involved primarily in response
      inhibition, then rIFC should exert an inhibitory influence over M1 on no-go
      (inhibition) trials regardless of no-go probability. If, by contrast, rIFC has a
      role on unexpected trials other than just response inhibition then rIFC should
      influence M1 on infrequent trials regardless of response demands. We observed
      that rIFC suppressed M1 excitability during frequent no-go trials, but not during
      infrequent no-go trials, suggesting that the role of rIFC in response inhibition
      is context dependent rather than generic. Importantly, rIFC was found to
      facilitate M1 excitability on all low frequent trials, irrespective of whether
      the infrequent event involved response inhibition, a finding more in line with a
      predictive coding framework of cognitive control. 

PMID- 24282399
TI  - Emotional reactions of peers influence decisions about fairness in adolescence.
AB  - During adolescence, peers take on increasing importance, while social skills are
      still developing. However, how emotions of peers influence social decisions
      during that age period is insufficiently known. We therefore examined the effects
      of three different emotional responses (anger, disappointment, happiness) on
      decisions about fairness in a sample of 156 adolescents aged 12-17 years.
      Participants received written emotional responses from peers in a version of the
      Dictator Game to a previous unfair offer. Adolescents reacted with more generous
      offers after disappointed reactions compared to angry and happy reactions.
      Furthermore, we found preliminary evidence for developmental differences over
      adolescence, since older adolescents differentiated more between the three
      emotions than younger adolescents. In addition, individual differences in social
      value orientation played a role in decisions after happy reactions of peers to a
      previous unfair offer, such that participants with a "proself" orientation made
      more unfair offers to happy peers than "prosocial" participants. Taken together,
      our findings demonstrate that adolescents take emotions of peers into account
      when making social decisions, while individual differences in social value
      orientation affect these decisions, and age seems to influence the nature of the
      reaction. 

PMID- 24282400
TI  - Long-latency TMS-evoked potentials during motor execution and inhibition.
AB  - Transcranial magnetic stimulation (TMS) has often been used in conjunction with
      electroencephalography (EEG), which is effective for the direct demonstration of
      cortical reactivity and corticocortical connectivity during cognitive tasks
      through the spatio-temporal pattern of long-latency TMS-evoked potentials (TEPs).
      However, it remains unclear what pattern is associated with the inhibition of a
      planned motor response. Therefore, we performed TMS-EEG recording during a
      go/stop task, in which participants were instructed to click a computer mouse
      with a right index finger when an indicator that was moving with a constant
      velocity reached a target (go trial) or to avoid the click when the indicator
      randomly stopped just before it reached the target (stop trial). Single-pulse TMS
      to the left (contralateral) or right (ipsilateral) motor cortex was applied 500
      ms before or just at the target time. TEPs related to motor execution and
      inhibition were obtained by subtractions between averaged EEG waveforms with and
      without TMS. As a result, in TEPs induced by both contralateral and ipsilateral
      TMS, small oscillations were followed by a prominent negative deflection around
      the TMS site peaking at approximately 100 ms post-TMS (N100), and a less
      pronounced later positive component (LPC) over the broad areas that was centered
      at the midline-central site in both go and stop trials. However, compared to the
      pattern in go and stop trials with TMS at 500 ms before the target time, N100 and
      LPC were differently modulated in the go and stop trials with TMS just at the
      target time. The amplitudes of both N100 and LPC decreased in go trials, while
      the amplitude of LPC decreased and the latency of LPC was delayed in both go and
      stop trials. These results suggested that TMS-induced neuronal reactions in the
      motor cortex and subsequent their propagation to surrounding cortical areas might
      change functionally according to task demand when executing and inhibiting a
      motor response. 

PMID- 24282401
TI  - Hierarchical vector auto-regressive models and their applications to multi
      subject effective connectivity.
AB  - Vector auto-regressive (VAR) models typically form the basis for constructing
      directed graphical models for investigating connectivity in a brain network with
      brain regions of interest (ROIs) as nodes. There are limitations in the standard
      VAR models. The number of parameters in the VAR model increases quadratically
      with the number of ROIs and linearly with the order of the model and thus due to
      the large number of parameters, the model could pose serious estimation problems.
      Moreover, when applied to imaging data, the standard VAR model does not account
      for variability in the connectivity structure across all subjects. In this paper,
      we develop a novel generalization of the VAR model that overcomes these
      limitations. To deal with the high dimensionality of the parameter space, we
      propose a Bayesian hierarchical framework for the VAR model that will account for
      both temporal correlation within a subject and between subject variation. Our
      approach uses prior distributions that give rise to estimates that correspond to
      penalized least squares criterion with the elastic net penalty. We apply the
      proposed model to investigate differences in effective connectivity during a hand
      grasp experiment between healthy controls and patients with residual motor
      deficit following a stroke. 

PMID- 24282402
TI  - A computational model for preplay in the hippocampus.
AB  - The hippocampal network produces sequences of neural activity even when there is
      no time-varying external drive. In offline states, the temporal sequence in which
      place cells fire spikes correlates with the sequence of their place fields.
      Recent experiments found this correlation even between offline sequential
      activity (OSA) recorded before the animal ran in a novel environment and the
      place fields in that environment. This preplay phenomenon suggests that OSA is
      generated intrinsically in the hippocampal network, and not established by
      external sensory inputs. Previous studies showed that continuous attractor
      networks with asymmetric patterns of connectivity, or with slow, local negative
      feedback, can generate sequential activity. This mechanism could account for
      preplay if the network only represented a single spatial map, or chart. However,
      global remapping in the hippocampus implies that multiple charts are represented
      simultaneously in the hippocampal network and it remains unknown whether the
      network with multiple charts can account for preplay. Here we show that it can.
      Driven with random inputs, the model generates sequences in every chart. Place
      fields in a given chart and OSA generated by the network are highly correlated.
      We also find significant correlations, albeit less frequently, even when the OSA
      is correlated with a new chart in which place fields are randomly scattered.
      These correlations arise from random correlations between the orderings of place
      fields in the new chart and those in a pre-existing chart. Our results suggest
      two different accounts for preplay. Either an existing chart is re-used to
      represent a novel environment or a new chart is formed. 

PMID- 24282403
TI  - Shorter term aerobic exercise improves brain, cognition, and cardiovascular
      fitness in aging.
AB  - Physical exercise, particularly aerobic exercise, is documented as providing a
      low cost regimen to counter well-documented cognitive declines including memory,
      executive function, visuospatial skills, and processing speed in normally aging
      adults. Prior aging studies focused largely on the effects of medium to long term
      (>6 months) exercise training; however, the shorter term effects have not been
      studied. In the present study, we examined changes in brain blood flow,
      cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of
      age) who were randomized into physical training or a wait-list control group. The
      physical training group received supervised aerobic exercise for 3 sessions per
      week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and
      resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and
      post-training (T3). We found higher resting CBF in the anterior cingulate region
      in the physical training group as compared to the control group from T1 to T3.
      Cognitive gains were manifested in the exercise group's improved immediate and
      delayed memory performance from T1 to T3 which also showed a significant positive
      association with increases in both left and right hippocampal CBF identified
      earlier in the time course at T2. Additionally, the two cardiovascular
      parameters, VO2 max and rating of perceived exertion (RPE) showed gains, compared
      to the control group. These data suggest that even shorter term aerobic exercise
      can facilitate neuroplasticity to reduce both the biological and cognitive
      consequences of aging to benefit brain health in sedentary adults. 

PMID- 24282404
TI  - Archaeal and bacterial communities in three alkaline hot springs in Heart Lake
      Geyser Basin, Yellowstone National Park.
AB  - The Heart Lake Geyser Basin (HLGB) is remotely located at the base of Mount
      Sheridan in southern Yellowstone National Park (YNP), Wyoming, USA and is
      situated along Witch Creek and the northwestern shore of Heart Lake. Likely
      because of its location, little is known about the microbial community structure
      of springs in the HLGB. Bacterial and archaeal populations were monitored via
      small subunit (SSU) rRNA gene pyrosequencing over 3 years in 3 alkaline (pH 8.5)
      hot springs with varying temperatures (44 degrees C, 63 degrees C, 75 degrees C).
      The bacterial populations were generally stable over time, but varied by
      temperature. The dominant bacterial community changed from moderately
      thermophilic and photosynthetic members (Cyanobacteria and Chloroflexi) at 44
      degrees C to a mixed photosynthetic and thermophilic community (Deinococcus
      Thermus) at 63 degrees C and a non-photosynthetic thermophilic community at 75
      degrees C. The archaeal community was more variable across time and was
      predominantly a methanogenic community in the 44 and 63 degrees C springs and a
      thermophilic community in the 75 degrees C spring. The 75 degrees C spring
      demonstrated large shifts in the archaeal populations and was predominantly
      Candidatus Nitrosocaldus, an ammonia-oxidizing crenarchaeote, in the 2007 sample,
      and almost exclusively Thermofilum or Candidatus Caldiarchaeum in the 2009
      sample, depending on SSU rRNA gene region examined. The majority of sequences
      were dissimilar (>=10% different) to any known organisms suggesting that HLGB
      possesses numerous new phylogenetic groups that warrant cultivation efforts. 

PMID- 24282406
TI  - Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting
      properties.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved
      in glycolysis and shown, particularly in animal cells, to play additional roles
      in several unrelated non-metabolic processes such as control of gene expression
      and apoptosis. This functional versatility is regulated, in part at least, by
      redox post-translational modifications that alter GAPDH catalytic activity and
      influence the subcellular localization of the enzyme. In spite of the well
      established moonlighting (multifunctional) properties of animal GAPDH, little is
      known about non-metabolic roles of GAPDH in plants. Plant cells contain several
      GAPDH isoforms with different catalytic and regulatory properties, located both
      in the cytoplasm and in plastids, and participating in glycolysis and the Calvin
      Benson cycle. A general feature of all GAPDH proteins is the presence of an
      acidic catalytic cysteine in the active site that is overly sensitive to
      oxidative modifications, including glutathionylation and S-nitrosylation. In
      Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as
      a tool to investigate the role of reduced glutathione, thioredoxins and
      glutaredoxins in the control of different types of redox post-translational
      modifications. Oxidative modifications inhibit GAPDH activity, but might enable
      additional functions in plant cells. Mounting evidence support the concept that
      plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are
      triggered by redox post-translational modifications of the protein under stress
      conditions. The aim of this review is to detail the molecular mechanisms
      underlying the redox regulation of plant cytoplasmic GAPDH in the light of its
      crystal structure, and to provide a brief inventory of the well known redox
      dependent multi-facetted properties of animal GAPDH, together with the emerging
      roles of oxidatively modified GAPDH in stress signaling pathways in plants. 

PMID- 24282407
TI  - Ubiquitination in plant nutrient utilization.
AB  - Ubiquitin (Ub) is well-established as a major modifier of signaling in
      eukaryotes. However, the extent to which plants rely on Ub for regulating
      nutrient uptake is still in its infancy. The main characteristic of
      ubiquitination is the conjugation of Ub onto lysine residues of acceptor
      proteins. In most cases the targeted protein is rapidly degraded by the 26S
      proteasome, the major proteolysis machinery in eukaryotic cells. The Ub
      proteasome system is responsible for removing most abnormal peptides and short
      lived cellular regulators, which, in turn, control many processes. This allows
      cells to respond rapidly to intracellular signals and changing environmental
      conditions. This perspective will discuss how plants utilize Ub conjugation for
      sensing environmental nutrient levels. We will highlight recent advances in
      understanding how Ub aids nutrient homeostasis by affecting the trafficking of
      membrane bound transporters. Given the overrepresentation of genes encoding Ub
      metabolizing enzymes in plants, intracellular signaling events regulated by Ub
      that lead to transcriptional responses due to nutrient starvation is an under
      explored area ripe for new discoveries. We provide new insight into how Ub based
      biochemical tools can be exploited to reveal new molecular components that affect
      nutrient signaling. The mechanistic nature of Ub signaling indicates that
      dominant form of any new molecular components can be readily generated and are
      likely shed new light on how plants cope with nutrient limiting conditions.
      Finally as part of future challenges in this research area we introduce the newly
      discovered roles of Ub-like proteins in nutrient homeostasis. 

PMID- 24282405
TI  - Human plasmacytoid dendritic cells: from molecules to intercellular communication
      network.
AB  - Plasmacytoid dendritic cells (pDCs) are a specific subset of naturally occurring
      dendritic cells, that secrete large amounts of Type I interferon and play an
      important role in the immune response against viral infection. Several studies
      have highlighted that they are also effective antigen presenting cells, making
      them an interesting target for immunotherapy against cancer. However, the modes
      of action of pDCs are not restricted to antigen presentation and IFN secretion
      alone. In this review we will highlight a selection of cell surface proteins
      expressed by human pDCs that may facilitate communication with other immune
      cells, and we will discuss the implications of these molecules for pDC-driven
      immune responses. 

PMID- 24282408
TI  - Serum AMH in Physiology and Pathology of Male Gonads.
AB  - AMH is secreted by immature Sertoli cells (SC) and is responsible for the
      regression of Mullerian ducts in the male fetus as part of the sexual
      differentiation process. AMH is also involved in testicular development and
      function. AMHs are at their lowest levels in the first days after birth but
      increase after the first week, likely reflecting active SC proliferation. AMH
      rises rapidly in concentration in boys during the first month, reaching a peak
      level at about 6 months of age, and then slowly declines during childhood,
      falling to low levels in puberty. Basal and FSH-stimulated levels of AMH, might
      become a useful predictive marker of the spermatogenic response to gonadotropic
      treatment in young patients with hypogonadotropic hypogonadism. After puberty,
      AMH is released preferentially by the apical pole of the SC towards the lumen of
      the seminiferous tubules, resulting in higher concentrations in the seminal
      plasma than in the serum. Defects in AMH production and insensitivity to AMH due
      to receptor defects result in the persistent Mullerian duct syndrome. A
      measurable value of AMH in a boy with bilateral cryptorchidism is predictive of
      undescended testes, while an undetectable value is highly suggestive of anorchia
      or ovaries, as would be the case in girls with female pseudohermaphroditism and
      pure gonadal dysgenesis. Lower serum AMH concentrations in otherwise healthy boys
      with cryptorchidism, who were compared with their age-matched counterparts with
      palpable testes, have been reported previously. AMH levels are higher in
      prepubertal patients with varicocele than in controls. This altered serum profile
      of AMH in boys with varicoceles may indicate an early abnormality in the
      regulation of the seminiferous epithelial function. Serum AMH is known to be
      valuable in assessing gonadal function. As compared to testing involving the
      administration of human chorionic gonadotropin, the measurement of AMH is more
      sensitive and equally specific. Measurement of AMH is very useful in young
      children, because serum gonadotropin concentrations in those who are agonadal are
      nondiagnostic in midchildhood and serum testosterone concentrations may fail to
      increase with provocative testing in children with abdominal testes. 

PMID- 24282410
TI  - Trends in Breast Cancer Incidence Rates by Age and Stage at Diagnosis in
      Gharbiah, Egypt, over 10 Years (1999-2008).
AB  - Background. This study was undertaken to evaluate trends in breast cancer
      incidence in Egypt from 1999 to 2008 and to make projections for breast cancer
      occurrence for the years 2009-2015. Patients and Methods. We utilized joinpoint
      regression and average annual percent change (AAPC) measures with 95% confidence
      intervals (CI) to describe the trends in breast cancer incidence rates from the
      Gharbiah Cancer Registry by age and stage at diagnosis and to estimate expected
      breast cancer caseloads for 2009-2015. Results. From 1999 to 2008, the AAPC in
      breast cancer incidence rates in Gharbiah significantly increased among women 50
      years and older and among localized tumors (AAPC %, 95% CI, 3.1% to 8.0%). Our
      results predict a significant increase in breast cancer caseloads from 2009 to
      2015 among women aged 30-39 (AAPC %, 95% CI, 0.9% to 1.1%) and among women aged
      40-49 years (AAPC %, 95% CI, 1.0% to 2.6%). Conclusion. These results have
      important implications for allocating limited resources, managing treatment
      needs, and exploring the consequences of prior interventions and/or changing risk
      factors in Egypt and other developing countries at the same stages of demographic
      and health transitions. 

PMID- 24282409
TI  - Potential biomarkers of insulin resistance and atherosclerosis in type 2 diabetes
      mellitus patients with coronary artery disease.
AB  - Type 2 diabetes mellitus patients with coronary artery disease have become a
      major public health concern. The occurrence of insulin resistance accompanied
      with endothelial dysfunction worsens the state of atherosclerosis in type 2
      diabetes mellitus patients. The combination of insulin resistance and endothelial
      dysfunction leads to coronary artery disease and ischemic heart disease
      complications. A recognized biological marker, high-sensitivity C-reactive
      protein, has been used widely to assess the progression of atherosclerosis and
      inflammation. Along with coronary arterial damage and inflammatory processes,
      high-sensitivity C-reactive protein is considered as an essential atherosclerosis
      marker in patients with cardiovascular disease, but not as an insulin resistance
      marker in type 2 diabetes mellitus patients. A new biological marker that can act
      as a reliable indicator of both the exact state of insulin resistance and
      atherosclerosis is required to facilitate optimal health management of diabetic
      patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads
      to innate immune activation and released several biological markers into
      circulation. This review examines potential biological markers, YKL-40, alpha
      hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding
      protein-4, and chemerin, as they may play significant roles in insulin resistance
      and atherosclerosis in type 2 diabetes mellitus patients with coronary artery
      disease. 

PMID- 24282411
TI  - The rate of decolorization of a radical ion reagent was used to determine the
      phenolic content of various food extracts.
AB  - Polyphenols are among the most valuable and widely studied food components. In
      the laboratory, they are readily extractable with aqueous alcohol. An aliquot
      rapidly decolorizes a measured portion of ABTS, a stable deep blue radical ion.
      The semilog plot of light absorption versus time is typically a straight line,
      and an immediately evident slope provides rapid classification in terms of gallic
      acid equivalents. Experimental data are presented to show general agreement with
      the literature. The disproportionate concentration of antioxidant in the skins
      and peels of fruits, vegetables, and nuts is given special attention. 

PMID- 24282412
TI  - Destroy and exploit: catalyzed removal of hydroperoxides from the endoplasmic
      reticulum.
AB  - Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases,
      hydroperoxide reduction is coupled to the formation of a disulfide bond, which is
      transferred onto specific acceptor molecules, the so-called reducing substrates.
      As such, peroxidases control the spatiotemporal distribution of diffusible second
      messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members
      of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases
      (GPxs), reside in different subcellular compartments or are secreted from cells.
      This review discusses the properties and physiological roles of PrxIV, GPx7, and
      GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2 and
      possibly-lipid hydroperoxides are regularly produced. Different peroxide sources
      and reducing substrates for ER peroxidases are critically evaluated. Peroxidase
      catalyzed detoxification of hydroperoxides coupled to the productive use of
      disulfides, for instance, in the ER-associated process of oxidative protein
      folding, appears to emerge as a common theme. Nonetheless, in vitro and in vivo
      studies have demonstrated that individual peroxidases serve specific,
      nonoverlapping roles in ER physiology. 

PMID- 24282414
TI  - DGGE Identification of Microorganisms Associated with Borrelia burgdorferi Sensu
      Lato- or Anaplasma phagocytophilum-Infected Ixodes ricinus Ticks from Northwest
      Norway.
AB  - Ticks acquire a wide range of microorganisms as a natural part of their
      lifecycle. Bacteria, viruses, and protozoa can be transmitted to ticks during
      feeding and free-living phases. DGGE profiling is a molecular method to describe
      the microbial population associated with ticks and demonstrate some of the
      complexity and variety of tick-borne microorganisms. The present study profiled a
      total of 120 I. ricinus ticks, which were divided into three equally sized
      groups. We found that B. burgdorferi s.l.-infected ticks presented a pattern
      consisting of bacterial Pseudomonas spp. (67.5%), Bacillus spp. (50%), and
      Sphingomonas spp. (77.5%), while A. phagocytophilum-infected ticks were
      associated with Pseudomonas spp. (82.5%) and Sphingomonas spp. (57.5%). All
      profiles had one or more Pseudomonas species present, and the intramitochondrial
      endosymbiont Candidatus Midichloria mitochondrii was present in more than 25% of
      the samples. Statistical analysis demonstrated that the microbial communities
      were not significantly different between the groups and that the groups could not
      be characterised by a specific microbial population. 

PMID- 24282413
TI  - Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins.
AB  - Prions are unconventional infectious agents that are composed of misfolded
      aggregated prion protein. Prions replicate their conformation by template
      assisted conversion of the endogenous prion protein PrP. Templated conversion of
      soluble proteins into protein aggregates is also a hallmark of other
      neurodegenerative diseases. Alzheimer's disease or Parkinson's disease are not
      considered infectious diseases, although aggregate pathology appears to progress
      in a stereotypical fashion reminiscent of the spreading behavior ofmammalian
      prions. While basic principles of prion formation have been studied extensively,
      it is still unclear what exactly drives PrP molecules into an infectious, self
      templating conformation. In this review, we discuss crucial steps in the life
      cycle of prions that have been revealed in ex vivo models. Importantly, the
      persistent propagation of prions in mitotically active cells argues that cellular
      processes are in place that not only allow recruitment of cellular PrP into
      growing prion aggregates but also enable the multiplication of infectious seeds
      that are transmitted to daughter cells. Comparison of prions with other protein
      aggregates demonstrates that not all the characteristics of prions are equally
      shared by prion-like aggregates. Future experiments may reveal to which extent
      aggregation-prone proteins associated with other neurodegenerative diseases can
      copy the replication strategies of prions. 

PMID- 24282416
TI  - Comparison of the systemic lupus erythematosus activity questionnaire and the
      systemic lupus erythematosus disease activity index in a black barbadian
      population.
AB  - In Barbados, use of the Systemic Lupus Erythematosus (SLE) Disease Activity Index
      (SLEDAI) is limited by the unavailability of serologic markers. The SLE Activity
      Questionnaire (SLAQ) excludes laboratory measurements and is therefore more
      accessible. Here, we investigate the agreement between the SLAQ, the SLEDAI, and
      the physician global assessment (PGA). A pilot of 32 participants completed the
      SLAQ and SLEDAI. The tools were compared (1) in their original format, (2)
      limited to common indices, and (3) limited to the same patient recall period. We
      compared the proportions of persons reporting disease activity and the
      concordance between calculated activity scores for SLAQ versus SLEDAI and for
      SLAQ versus PGA. Seventy-eight percent versus 59% of participants reported
      disease activity with the original SLEDAI versus SLAQ, respectively. The
      relationship was reversed to 22% versus 59% when the matched item tools were
      compared. Concordance was 0.62 (95% CI 0.42-0.81) between the original scores,
      0.70 (0.57-0.83) when restricted by matched items, and 0.72 (0.59-0.84) when
      further restricted by recall period. Concordance between the SLAQ and PGA was
      0.56 (0.32-0.80). Reversal of the disease activity percentage in the matched
      items comparison highlights the inadequacy of tools that exclude laboratory
      measurements and suggests that the subjective nature of SLAQ may contribute to
      over-reporting. Further work is needed to produce a robust disease activity tool
      apt for resource-constrained environments. 

PMID- 24282417
TI  - Feasibility of RNA and DNA extraction from fresh pipelle and archival endometrial
      tissues for use in gene expression and SNP arrays.
AB  - Identifying molecular markers of endometrial hyperplasia (neoplasia) progression
      is critical to cancer prevention. To assess RNA and DNA quantity and quality from
      routinely collected endometrial samples and evaluate the performance of RNA- and
      DNA-based arrays across endometrial tissue types, we collected fresh frozen (FF)
      Pipelle, FF curettage, and formalin-fixed paraffin-embedded (FFPE) hysterectomy
      specimens (benign indications) from eight women. Additionally, neoplastic and
      uninvolved tissues from 24 FFPE archival hysterectomy specimens with endometrial
      hyperplasias and carcinomas were assessed. RNA was extracted from 15 of 16 FF and
      51 of 51 FFPE samples, with yields >1.2  MU g for 13/15 (87%) FF and 50/51 (98%)
      FFPE samples. Extracted RNA was of high quality; all samples performed
      successfully on the Illumina whole-genome cDNA-mediated annealing, selection,
      extension, and ligation (WG-DASL) array and performance did not vary by tissue
      type. While DNA quantity from FFPE samples was excellent, quality was not
      sufficient for successful performance on the Affymetrix SNP Array 6.0. In
      conclusion, FF Pipelle samples, which are minimally invasive, yielded excellent
      quantity and quality of RNA for gene expression arrays (similar to FF curettage)
      and should be considered for use in genomic studies. FFPE-derived DNA should be
      evaluated on new rapidly evolving sequencing platforms. 

PMID- 24282415
TI  - Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and
      therapeutic issues.
AB  - Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system
      dysregulation leading to aberrant inflammasome activation and episodes of fever
      and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract,
      and nervous system, predominantly with a childhood onset. To date, there are
      twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor
      associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells
      syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated
      autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome,
      Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of
      these conditions may manifest itself with more or less severe inflammatory
      symptoms of variable duration and frequency, associated with findings of
      increased inflammatory parameters in laboratory investigation. The purpose of
      this paper is to describe the main genetic, clinical, and therapeutic aspects of
      MAISs and their most recent classification with the ultimate goal of increasing
      awareness of autoinflammation among various internal medicine specialists. 

PMID- 24282418
TI  - Generalized lymphadenopathy as the first presentation of granulocytic sarcoma: a
      diagnostic challenge.
AB  - Introduction. Granulocytic sarcoma (GS), also known as chloroma or extramedullary
      myeloblastoma, is a solid tumor composed of primitive precursors of the
      granulocytic series that include myeloblasts, promyelocytes, and myelocytes.
      Granulocytic sarcoma is a rare tumor that may develop during acute myeloid
      leukemia (AML) but less frequently may precede its presentation. Although
      generalized lymph node enlargement is a presentation for malignant lymphoma, it
      can also rarely be the early presenting sign of GS. Methods. We present a case of
      GS mimicking lymphoma in a 45-year-old male. The patient presented with bilateral
      neck masses and had widespread, prominent lymphadenopathy secondary to AML as the
      first presenting manifestation of GS for the last 4 months with concurrent marrow
      AML. Result. A clinical diagnosis of lymphoma was suspected; fine needle
      aspiration cytology findings were also suggestive of lymphoma. However,
      peripheral blood and bone marrow examination reported as acute myeloid leukemia
      with monocytic differentiation and histopathology of excised lymph node confirmed
      it to be a GS not lymphoma. Conclusion. GS is often misdiagnosed as malignant
      lymphoma because of cytomorphologic and histologic similarities of the blasts to
      large cell lymphoma. A careful search for immature myeloid is a useful clue to
      the diagnosis accompanied with appropriate immunophenotyping. 

PMID- 24282419
TI  - Kawasaki Disease: A Clinician's Update.
AB  - Aims. Kawasaki disease is an acute systemic vasculitis and is the most common
      cause of acquired heart disease in children in the developed world. This review
      aims to synthesise recent insights into the disease and provide an update for
      clinicians on diagnostic and treatment practices. Methods. We conducted a review
      of the literature exploring epidemiology, aetiology, diagnosis, and management of
      Kawasaki disease. We searched MEDLINE, Medline In-Process, Embase, Google
      Scholar, and reference lists of relevant articles. Conclusions. Kawasaki disease
      is a febrile vasculitis which progresses to coronary artery abnormalities in 25%
      of untreated patients. The disease is believed to result from a genetically
      susceptible individual's exposure to an environmental trigger. Incidence is
      rising worldwide, and varies widely across countries and within different ethnic
      groups. Diagnosis is based on the presence of fever in addition to four out of
      five other clinical criteria, but it is complicated by the quarter of the
      Kawasaki disease patients with "incomplete" presentation. Treatment with
      intravenous immunoglobulin within ten days of fever onset improves clinical
      outcomes and reduces the incidence of coronary artery dilation to less than 5%.
      Given its severe morbidity and potential mortality, Kawasaki disease should be
      considered as a potential diagnosis in cases of prolonged paediatric fever. 

PMID- 24282420
TI  - Cost-effectiveness analysis of adding low dose ribavirin to peginterferon alfa-2a
      for treatment of chronic hepatitis C infected thalassemia major patients in iran.
AB  - BACKGROUND: The prevalence of hepatitis C in Iran is 1% and 18% in general
      population and thalassemia patients respectively. The cost effectiveness analysis
      of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination
      treatment strategy of chronic hepatitis C in thalassemia patients in comparison
      with monotherapy could help clinicians and policy makers to provide the best
      treatment for the patients. OBJECTIVES: In this study we aimed to assess whether
      adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different
      genotypes and different subgroups of 280 patients with chronic hepatitis C
      infection from the perspective of society in Iranian setting. PATIENTS AND
      METHODS: A cost effectiveness analysis including all costs and outcomes of
      treatments for chronic hepatitis C infected thalassemia major patients was
      conducted. We constructed a decision tree of treatment course in which a
      hypothetical cohort of 100 patients received "PEG IFN alfa-2a" or "Peg IFN alfa
      2a plus Ribavirin." The cost analysis was based on cost data for 2008 and we used
      9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central
      Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a
      strategy is cost effective, one time and three times of GDP per capita were used
      as threshold based on recommendation of the World Health Organization. RESULTS:
      The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in
      genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD)
      per one Sustain Virological Response (SVR), respectively. In low viral load and
      high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR,
      respectively. The calculated ICER for combination therapy in subgroup of patients
      with previously resistant to monotherapy was 13,006 USD per SVR. Combination
      therapy in previously resistant patients to combination therapy was a dominant
      strategy. CONCLUSIONS: Adding low dose of Ribavirin to PEG IFN alfa-2a for
      treatment of chronic hepatitis C patients with genotype-1 was "highly cost
      effective" and in patients with low viral load and in previous monotherapy
      resistant patients was "cost effective."

PMID- 24282421
TI  - Metronomic capecitabine in patients with hepatocellular carcinoma unresponsive to
      or ineligible for sorafenib treatment: report of two cases.
AB  - INTRODUCTION: Sorafenib, an oral multikinase inhibitor, is the only systemic
      agent proven to be effective in patients with hepatocellular carcinoma (HCC).
      There are no approved second line systemic therapies in patients who have had
      disease progression on or are not eligible to sorafenib. CASE PRESENTATION: We
      describe two cases of unresectable HCC that were treated with low, "metronomic"
      doses of capecitabine. In the first patient, capecitabine was used after
      sorafenib failure. In the second case, treatment with capecitabine was attempted
      since the patient was considered not eligible for sorafenib due to spontaneous
      hepatic bleeding of a large HCC lesion. Treatment was effective and well
      tolerated in both patients with long-lasting objective responses. CONCLUSIONS:
      Lacking established second-line therapy, metronomic capecitabine may be a valid
      alternative in the treatment of HCC patients who are judged not eligible for
      sorafenib or those having progression disease on sorafenib.

PMID- 24282422
TI  - Diagnostic Performance of Two Point-of-Care Tests for Anti-HCV Detection.
AB  - BACKGROUND: Besides the great importance of the issue in terms of public health,
      there is a lack of studies evaluating the performance of several of the currently
      used point of care tests (POCTs) for the detection of anti-HCV. OBJECTIVES: To
      investigate the performance of two POCTs for anti-HCV detection and to assess the
      impact of the reading time on diagnostic performance. PATIENTS AND METHODS: A
      total of 307 subjects were divided into three groups (1- HCV infected; 2- other
      chronic liver diseases; and 3- controls). The POCTs HCV Rapid Test Bioeasy(r) and
      Imuno-Rapido HCV(r) were read at 3, 5, 10, 15, 20 and 30 minutes. The sensitivity
      and specificity of the POCTs were calculated in relation to anti-HCV detection by
      chemiluminescence. RESULTS: Valid results were obtained for all tests. When
      compared to the chemiluminescence, both tests showed sensitivity of 97.1% and
      specificity of 100%. No changes in the sensitivity or specificity of the tests
      were observed at different reading times and when patients with other chronic
      liver diseases were evaluated as a control group. CONCLUSIONS: The POCTs
      evaluated in this study showed high sensitivity and specificity, with no change
      in the performance after the third minute of reading.

PMID- 24282423
TI  - The N-Glycosylation Modification of LHBs (Large Surface Proteins of HBV) Effects
      on Endoplasmic Reticulum Stress, Cell Proliferation and its Secretion.
AB  - BACKGROUND: The mutations of LHBs in pre-S, especially in pre-S2, are definitive
      in hepatocellular carcinoma (HCC) associated with HBV. However, the mechanisms of
      the N-glycosylation modification in LHBs are unclear. The N-glycosylation
      modification of LHBs affects Endoplasmic Reticulum stress, cell proliferation and
      its secretion which was further studied. OBJECTIVES: The objectives of our
      studies was to indentified that modification of LHBs by N glycosylation modulate
      their secretion, affect ER stress or expression of cycling, cell cycle and
      proliferation. MATERIALS AND METHODS: The LHBs was mutated; then expression of
      proteins related to endoplasmic reticulum stress and EAED path of L02 cells
      affected by LHBs and its mutations was evaluated. LHBs proteins bound to
      multiubiquitin chains and its glycosylation motif were studied. The subcellular
      localization and secretion of LHBs and its mutations were identified. The effect
      on cell cycle and proliferation by LHBs and its mutations were detected. RESULTS:
      These data demonstrated that the N-glycosylation motifs of LHBs were associated
      with ER stress. The N15S, N123S, and N177S mutated LHBs proteins could induce
      overexpression of EDEM in L02 cells. LHBs and its mutated proteins contained p62
      derived UBA domain, which could affect expression of cyclins. The subcellular
      localization of LHBs in endoplasmic reticulum was similar to its mutations. The
      secretion of LHBs was blocked by N320K mutation, which could induce an increase
      in G1 phase and inhibition of S phase, and inhibited mitotic entry. CONCLUSIONS:
      In conclusion, our studies powerfully demonstrated that modification of LHBs by N
      glycosylation could modulate their secretion, affect ER stress or expression of
      cycling, cell cycle and proliferation. The N320K may be the key sites N-linked
      glycosylation modification of LHBs. It may be a mechanism of HBV-induced HCC.

PMID- 24282424
TI  - Association of Hepatitis B Virus Mutations of A1846T and C1913A/G With Acute-on
      Chronic Liver Failure Development From Different Underlying Chronic Liver
      Diseases.
AB  - BACKGROUND: As most HBV-related acute-on-chronic liver failure (ACLF) have
      concurrent cirrhosis, it is important to clarify the association of viral factors
      with ACLF with or without cirrhosis. OBJECTIVES: The aim of this study was to
      analyze the association of HBV genotypes and mutations with ACLF development
      underlying different chronic liver diseases. PATIENTS AND METHODS: Eighty-seven
      ACLF patients including 29 patients with chronic hepatitis (ACLF-CHB) and 58
      patients with liver cirrhosis (ACLF-LC) were enrolled. Age and sex matched
      patients with chronic hepatitis (CHB) and liver cirrhosis (LC) were enrolled as
      controls. The genotypes and mutations at HBV basic core promoter (BCP), precore
      (PC), and partial C regions were determined by nested PCR and direct sequencing.
      RESULTS: Our results revealed significantly higher incidences (P < 0.05) of
      genotype B with C1913A/G or A1846T in patients with ACLF-CHB than those with CHB;
      genotype C with C1913A/G or A1846T in patients with ACLF-CHB and ACLF-LC than
      those with CHB and LC, respectively. Multivariable analysis indicated that A1846T
      and C1913A/G mutations were independent factors for ACLF (OR = 2.86 and 5.93,
      respectively), suggesting an association between the mutations and development of
      ACLF. In addition, there were no significant differences in mutations at T1753V,
      A1762T, G1764A, G1896A, and G1899A which were found between either CHB and ACLF
      CHB or LC and ACLF-LC patients, suggesting no associations of these mutations
      with ACLF development. CONCLUSIONS: Our findings suggest that CHB or LC patients
      infected with HBV A1846T and C1913A/G mutants are more susceptible to develop
      ACLF.

PMID- 24282425
TI  - The effect of octreotide on urine output during orthotopic liver transplantation
      and early postoperative renal function; a randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Maintenance of the adequate intraoperative renal perfusion is very
      important during Orthotopic Liver Transplantation (OLT) to prevent acute renal
      failure. OBJECTIVES: For the first time, this study was designed to survey the
      effects of octreotide on urine output during anesthesia for OLT and early
      postoperative renal function. PATIENTS AND METHODS: In this randomized double
      blind placebo controlled clinical trial, 79 of 89 patients who underwent OLT and
      fulfilled the study requirement were randomly allocated into two groups. In the
      octreotide group, the patients received octreotide infusion from the start of the
      operation. On the other hand, the control group patients received physiologic
      saline infusion instead of octreotide. The Mean Arterial Pressure (MAP), heart
      rate, urine output, norepinephrine usage, and dosage during the three stages of
      OLT, and baseline and postoperative creatinine were recorded and compared between
      the two groups. RESULTS: No significant differences were found between the two
      groups regarding the demographic characteristics and graft factors (P > 0.05).
      However, urine output and MAP during the three stages of OLT were significantly
      higher in the octreotide group compared to the control group (P < 0.05).
      Moreover, no significant difference was observed between the two groups regarding
      baseline as well as postoperative creatinine (P > 0.05). CONCLUSIONS: The results
      demonstrated that octreotide infusion during anesthesia for OLT not only
      augmented the vasoconstriction effect of norepinephrine to increase MAP, but also
      maintained better renal perfusion and urine output during the operation.

PMID- 24282426
TI  - A new style of dimethylnitrosamine induced fulminant hepatitis in mice.
AB  - BACKGROUND: There is still no suitable mice model that can completely mimic the
      human fulminant hepatitis, which sets a block for drug effect evaluation and
      mechanism researching of human fulminant hepatitis. OBJECTIVES: The aim of this
      study was to establish an animal model able to mimic the main features of human
      fulminant hepatitis. MATERIALS AND METHODS: Dimethylnitrosamine (DMN) was
      peritoneally injected to mice for liver injury induction. Serum biochemicals, and
      Prothrombin Time were tested, and Prothrombin activity was calculated, the liver
      tissue pathological changes were evaluated via macroscopic view observation, HE
      staining, immunochemical staining, and electron microscopy observation. The mRNA
      levels of TNF-a, Fas, and IL-1beta were tested with quantitative PCR assay.
      RESULTS: The serum levels of both ALT and AST were elevated significantly and
      showed a high plateau. Liver pathological changes were progressed before 48 hours
      post DMN injection and then started to restore. The mRNA and protein expression
      levels of TNF-alpha and IL-1beta were significantly elevated. The PT started to
      extend from 36 hours and PTA was lower than 40% from then on. CONCLUSIONS: This
      kind of DMN induced mice liver injury is similar to human fulminant hepatitis in
      main features. This work provided a mice model which could mimic human fulminant
      hepatitis, and could be valuable for fulminant hepatitis mechanism research and
      liver protection drug evaluation.

PMID- 24282427
TI  - Distribution of hepatitis C virus genotypes among azerbaijani patients in capital
      city of iran-tehran.
AB  - BACKGROUND: Determination of the Hepatitis C virus (HCV) genotype distributed in
      a particular area has an important role on public health throughout the world.
      OBJECTIVES: The aim of this study was to determine the frequency of HCV genotypes
      in Azerbaijani patients. PATIENTS AND METHODS: From March 2010 until March 2012,
      235 Azerbaijani patients with established chronic hepatitis C, referred to
      Hospitals related to Iran University of Medical Sciences and Tehran Hepatitis
      Center, Clinical department of Baqiyatallah Research Center for Gastroeneterology
      and Liver Disease, were enrolled in this cross sectional study. About 5 mL of
      peripheral blood was collected from patients and after separation of plasma,
      viral RNA extracted. HCV-RNA were amplified by RT-nested PCR using primers from
      the 5'-UTR and genotyped by RFLP assay, and then HCV genotypes were confirmed
      using sequencing of cloned PCR products into pJET1.2/blunt cloning vector.
      RESULTS: HCV genotyping of positive plasma samples demonstrated that predominant
      HCV subtype was noted for 1b (71.1%) followed by subtype 3a (17.0%), genotype 2
      (6.8%), 1a (1.7%), and mixed infection (3.4%). The mean +/- SD age of patients
      was 37.3 +/- 11.8 (range: 2-63) years. Out of 235 patients, 139 (59.1%) were
      male. The frequency of HCV subtype 3a was higher in patients under 40 years old
      (3a: 18.1% vs. 15.0%), and subtype 3a was higher in male patients (3a: 18.7% vs.
      14.6%). CONCLUSIONS: The current study shows that the predominant HCV genotype
      among Azerbaijani patients with established chronic hepatitis C is subtype 1b
      (71.1%) followed by subtype 3a (17.0%).

PMID- 24282428
TI  - Consequences of international sanctions on Iranian scientists and the basis of
      science.

PMID- 24282429
TI  - Indoleamine 2,3-dioxygenase: expressing cells in inflammatory bowel disease-a
      cross-sectional study.
AB  - AIM: To characterise and enumerate IDO(+) cells, Tregs, and T cell subsets in
      patients with ulcerative colitis (UC) and Crohn's disease (CD) with regard to
      their clinical activity. METHODS: Ten active UC (aUC), 10 inactive UC (iUC), 6
      aCD, and 8 iCD patients and 10 healthy individuals were included in the study.
      Circulating Foxp3-, IDO-, IL-17A-, IL-4-, IFN- gamma -, and IL-10-expressing
      CD4(+) T cells were quantitated by flow cytometry. Interleukin-17-expressing
      cells, CD25(+)/Foxp3(+) Tregs, and CD123(+)/IDO(+) plasmacytoid dendritic cells
      were evaluated in intestinal biopsies from 10 aUC, 6 aCD, and 10 noninflamed
      tissues. RESULTS: All CD4(+) T subsets were increased in aIBD patients compared
      with healthy donors. Meanwhile, frequency of CD8 alpha (+)/CD16(+)/IDO(+), CD8
      alpha (+)/CD56(+)/IDO(+), CD8 alpha (+)/CD80(+)/IDO(+), CD8 alpha
      (+)/CD123(+)/IDO(+) large granular nonlymphoid cells, and CCR6(+)/CD123(+)/IDO(+)
      plasmacytoid dendritic cells was higher in aIBD patients versus healthy donors or
      iIBD patients. Tissue IL-17A(+) cells were present in higher amounts in aIBD
      versus noninflamed controls. IDO- and Foxp3-expressing cells were increased in
      aUC versus aCD patients and noninflamed tissues. CONCLUSIONS: The findings
      represent an original work in Mexican Mestizo patients with IBD. It shows that
      Tregs and IDO-expressing cells are increased with regard to disease activity.
      These cells could significantly shape inflammatory bowel disease pathophysiology,
      severity, and tolerance loss.

PMID- 24282430
TI  - Protective effects of HBSP on ischemia reperfusion and cyclosporine a induced
      renal injury.
AB  - Ischemia reperfusion (IR) and cyclosporine A (CsA) injuries are unavoidable in
      kidney transplantation and are associated with allograft dysfunction. Herein, the
      effect and mechanism of a novel tissue protective peptide, helix B surface
      peptide (HBSP) derived from erythropoietin, were investigated in a rat model. The
      right kidney was subjected to 45 min ischemia, followed by left nephrectomy and 2
      week reperfusion, with or without daily treatment of CsA 25 mg/kg and/or HBSP 8
      nmol/kg. Blood urea nitrogen was increased by CsA but decreased by HBSP at 1 week
      and 2 weeks, while the same changes were revealed in urinary protein/creatinine
      only at 2 weeks. HBSP also significantly ameliorated tubulointerstitial damage
      and interstitial fibrosis, which were gradually increased by IR and CsA. In
      addition, apoptotic cells, infiltrated inflammatory cells, and active caspase-3+
      cells were greatly reduced by HBSP in the both IR and IR + CsA groups. The 17 kD
      active caspase-3 protein was decreased by HBSP in the IR and IR + CsA kidneys,
      with decreased mRNA only in the IR + CsA kidneys. Taken together, it has been
      demonstrated, for the first time, that HBSP effectively improved renal function
      and tissue damage caused by IR and/or CsA, which might be through reducing
      caspase-3 activation and synthesis, apoptosis, and inflammation. 

PMID- 24282431
TI  - Physical demand profiles of hatha yoga postures performed by older adults.
AB  - Understanding the physical demands placed upon the musculoskeletal system by
      individual postures may allow experienced instructors and therapists to develop
      safe and effective yoga programs which reduce undesirable side effects. Thus, we
      used biomechanical methods to quantify the lower extremity joint angles, joint
      moments of force, and muscle activities of 21 Hatha yoga postures, commonly used
      in senior yoga programs. Twenty older adults, 70.7 years +/- 3.8 years,
      participated in a 32-wk yoga class (2 d/wk) where they learned introductory and
      intermediate postures (asanas). They then performed the asanas in a motion
      analysis laboratory. Kinematic, kinetic, and electromyographic data was collected
      over three seconds while the participants held the poses statically. Profiles
      illustrating the postures and including the biomechanical data were then
      generated for each asana. Our findings demonstrated that Hatha yoga postures
      engendered a range of appreciable joint angles, JMOFs, and muscle activities
      about the ankle, knee, and hip, and that demands associated with some postures
      and posture modifications were not always intuitive. They also demonstrated that
      all of the postures elicited appreciable rectus abdominis activity, which was up
      to 70% of that induced during walking. 

PMID- 24282432
TI  - Composition and Antidiarrheal Activity of Bidens odorata Cav.
AB  - The antidiarrheal effects of chloroform, methanol, and aqueous extracts of Bidens
      odorata Cav. were investigated at doses of 200 mg/kg on castor-oil-induced
      diarrhea. The chloroform extract of B. odorata (CBO) reduced diarrhea by 72.72%.
      The effect of CBO was evaluated on mice with diarrhea induced by castor oil,
      MgSO4, arachidonic acid, or prostaglandin E2. CBO inhibited the contraction
      induced by carbachol chloride on ileum (100 ug/mL) and intestinal transit (200
      mg/kg) in Wistar rats. The active fraction of CBO (F4) at doses of 100 mg/kg
      inhibited the diarrhea induced by castor oil (90.1%) or arachidonic acid (72.9%)
      but did not inhibit the diarrhea induced by PGE2. The active fraction of F4 (FR5)
      only was tested on diarrhea induced with castor oil and inhibited this diarrhea
      by 92.1%. The compositions of F4 and FR5 were determined by GC-MS, and oleic,
      palmitic, linoleic, and stearic acids were found. F4 and a mixture of the four
      fatty acids inhibited diarrhea at doses of 100 mg/kg (90.1% and 70.6%, resp.).
      The results of this study show that B. odorata has antidiarrheal effects, as is
      claimed by folk medicine, and could possibly be used for the production of a
      phytomedicine. 

PMID- 24282433
TI  - Cortex Moutan Induces Bladder Cancer Cell Death via Apoptosis and Retards Tumor
      Growth in Mouse Bladders.
AB  - Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal
      medicine widely used in Traditional Chinese Medicine for the treatment of blood
      heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex
      Moutan has anticancer effect. In this study, the Cortex Moutan extract was
      evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract
      reduces cell viability with IC50 between 1~2 mg/ml in bladder cancer cells, and
      it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S
      phase and causes phosphatidylserine expression in the outside of cell membrane.
      It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase
      degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced
      cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In
      mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan
      decreases the bladder tumor size without altering the blood biochemical
      parameters. In summary, these results demonstrate the antiproliferation and anti
      invasion properties of Cortex Moutan in bladder cancer cells and its antibladder
      tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic
      strategy for the intravesical therapy of superficial bladder cancer. 

PMID- 24282434
TI  - Curative Effects of ZHENG-Based Fuzheng-Huayu Tablet on Hepatitis B Caused
      Cirrhosis Related to CYP1A2 Genetic Polymorphism.
AB  - Aim. To investigate the correlation of Fuzheng-Huayu tablet (FZHY) efficacy on
      chronic hepatitis B caused cirrhosis (HBC) and single nucleotide polymorphisms
      (SNPs) of CYP1A2. Methods. After 111 cases of HBC with 69 excess, 21 deficiency
      excess, and 21 deficiency ZHENGs (ZHENG, also called traditional Chinese medicine
      syndrome) were treated by FZHY for 6 months, clinical symptoms, Child-Pugh score,
      and ZHENG score were observed. Three of the SNPs in CYP1A2 gene were detected and
      analyzed using SNaPshot assay. Results. In ZHENG efficacy between effective and
      invalid groups, there was significant difference (P < 0.001). The ZHENG
      deficiency was significantly correlated with FZHY efficacy (P < 0.05). AA
      genotype of CYP1A2-G2964A was significantly different with GG genotype (P < 0.05)
      between CYP1A2 Genotypes and FZHY efficacy on ZHENG. More importantly, GA plus AA
      genotype of CYP1A2-G2964A was significantly different with deficiency ZHENG (P <
      0.05) between CYP1A2 genotypes and FZHY efficacy on ZHENG. Conclusion. FZHY
      improved ZHENG score of HBC, and these efficacies may relate to CYP1A2-G2964A
      sites. It was suggested that CYP1A2-G2964A locus is probably a risk factor for
      ZHENG-based FZHY efficacy in HBC. 

PMID- 24282435
TI  - Complementary and alternative medicine for diseases and disorders in digestive
      tract: basic to clinics.

PMID- 24282436
TI  - Traditional chinese medicine diagnosis "yang-xu zheng": significant prognostic
      predictor for patients with severe sepsis and septic shock.
AB  - Pathogenesis of sepsis includes complex interaction between pathogen activities
      and host response, manifesting highly variable signs and symptoms, possibly
      delaying diagnosis and timely life-saving interventions. This study applies
      traditional Chinese medicine (TCM) Zheng diagnosis in patients with severe sepsis
      and septic shock to evaluate its adaptability and use as an early predictor of
      sepsis mortality. Three-year prospective observational study enrolled 126 septic
      patients. TCM Zheng diagnosis, Acute Physiology and Chronic Health Evaluation
      (APACHE) II score, and blood samples for host response cytokines measurement
      (tumor necrosis factor- alpha , Interleukin-6, Interleukin-8, Interleukin-10,
      Interleukin-18) were collected within 24 hours after admission to Intensive Care
      Unit. Main outcome was 28-day mortality; multivariate logistic regression
      analysis served to determine predictive variables of the sepsis mortality. APACHE
      II score, frequency of Nutrient-phase heat, and Qi-Xu and Yang-Xu Zhengs were
      significantly higher in nonsurvivors. The multivariate logistic regression
      analysis identified Yang-Xu Zheng as the outcome predictor. APACHE II score and
      levels of five host response cytokines between patients with and without Yang-Xu
      Zheng revealed significant differences. Furthermore, cool extremities and weak
      pulse, both diagnostic signs of Yang-Xu Zheng, were also proven independent
      predictors of sepsis mortality. TCM diagnosis "Yang-Xu Zheng" may provide a new
      mortality predictor for septic patients. 

PMID- 24282437
TI  - Modeling and simulating dynamics of complete- and poor-response chronic hepatitis
      B chinese patients for adefovir and traditional chinese medicine plus adefovir
      therapy.
AB  - ChiCTR-TRC-11001263 study was the first large-scale double-blind randomized
      placebo-controlled traditional Chinese medicines (TCMs) and adefovir (ADV)
      antihepatitis B virus (HBV) infection trial in the world. A total of 560
      hepatitis B e antigen- (HBeAg-) positive Chinese patients with chronical HBV were
      randomly classified, in 1 : 1 ratio, into two groups: experimental group (EXG)
      receiving TCMs + ADV and controlled group (CTG) receiving ADV + TCM-placebo
      treatment for 48 weeks. This paper introduces two models to model and simulate
      the evolutions of dynamics for the complete-response patients and the poor
      response patients in EXG and CTG, respectively. The stimulated mean HBV DNA and
      alanine aminotransferase (ALT) levels were close to the patients' experimental
      data. Analysis and simulations suggest that the activated patients' immune
      functions by TCMs + ADV may not only clear infected hepatocytes, but also clear
      HBV, which made the complete-response patients' mean serum HBV DNA levels in EXG
      reduce rapidly 12 weeks' earlier than the ones in CTG. One can assume that both
      the TCMs and ADV have the function of preventing complete-response patients'
      infected hepatocytes from being injured by cytotoxic T lymphocytes (CTLs); the
      patients' activated immune cells may also block HBV replications. 

PMID- 24282438
TI  - Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury
      Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.
AB  - Mechanisms for Panax ginseng's cardioprotective effect against ischemia
      reperfusion injury involve the estrogen-mediated pathway, but little is known
      about the role of androgen. A standardized Panax ginseng extract (RSE) was orally
      given with or without flutamide in a left anterior descending coronary artery
      ligation rat model. Infarct size, CK and LDH activities were measured. Time
      related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration
      were also investigated. RSE (80 mg/kg) significantly inhibited myocardial
      infarction and CK and LDH activities, while coadministration of flutamide
      abolished this effect of RSE. NO was increased by RSE and reached a peak after 15
      min of ischemia; however, flutamide cotreatment suppressed this elevation.
      Western blot analysis showed that RSE significantly reversed the decreases of
      expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas
      flutamide attenuated the effects of these protective mechanisms induced by RSE.
      RSE completely reversed the dropping of endogenous testosterone level induced by
      I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also
      produced a dramatic change on endogenous testosterone level after pretreatment
      and ischemia. Our results for the first time indicate that blocking androgen
      receptor abolishes the ability of Panax ginseng to protect the heart from
      myocardial I/R injury. 

PMID- 24282439
TI  - Solute diffusion and interactions in cross-linked poly(ethylene glycol) hydrogels
      studied by Fluorescence Correlation Spectroscopy.
AB  - Controlled diffusion and release of soluble molecules is one of the key
      challenges in developing three-dimensional (3D) scaffolds for tissue engineering
      and drug delivery applications in part because current methods to measure dynamic
      transport properties are difficult to perform directly, are strongly affected by
      the experimental setup, and therefore can be a subject to various artifacts. In
      this work we present a method for direct measurement of translational diffusion
      of solutes, namely Fluorescence Correlation Spectroscopy (FCS), by characterizing
      the diffusion of model proteins through a 3D cross-linked poly(ethylene glycol)
      (PEG) hydrogel scaffold. We examined both the dynamics of hydrogel structure
      (e.g., cross-linking and swelling) as well as protein size and their effect on
      protein diffusivity. For example, we demonstrated that protein diffusivity was
      closely related to protein size as smaller proteins (e.g., lysozyme) diffused
      faster than larger proteins (e.g., gamma-globulin or Ig). We validated the FCS
      protein diffusivity results by comparison to standard bulk diffusion assays.
      Additionally, due to the nature of FCS measurements, we were able to probe for
      hydrogel-protein interactions during cross-linking that may contribute to the
      obstructed protein diffusion in the 3D scaffold. We determined that such
      interactions in this system were not covalent (i.e., were independent of the
      cross-linking chemistry) but may be due to weaker hydrogen bonding or ionic
      interactions. Also, these interactions were protein specific and contributed up
      to 25% of the total decrease in protein diffusivity in the hydrogel as compared
      to diffusivity in water. Though interactions between various proteins and PEG
      have been reported, this is the first study that has explored these effects in
      detail in cross-linked PEG hydrogels using FCS; our findings question the
      assumption that PEG hydrogels are completely inert to protein interactions when
      applied as drug delivery matrices and tissue engineering scaffolds.

PMID- 24282440
TI  - A low-dimensional model for the red blood cell.
AB  - The red blood cell (RBC) is an important determinant of the rheological
      properties of blood because of its predominant number density, special mechanical
      properties and dynamics. Here, we develop a new low-dimensional RBC model based
      on dissipative particle dynamics (DPD). The model is constructed as a closed
      torus-like ring of 10 colloidal particles connected by wormlike chain springs
      combined with bending resistance. Each colloidal particle is represented by a
      single DPD particle with a repulsive core. The model is able to capture the
      essential mechanical properties of RBCs, and allows for economical exploration of
      the rheology of RBC suspensions. Specifically, we find that the linear and non
      linear elastic deformations of healthy and malaria-infected cells match those
      obtained in optical tweezers experiments. Through simulations of some key
      features of blood flow in vessels, i.e., the cell-free layer (CFL), the Fahraeus
      effect and the Fahraeus-Lindqvist effect, we verify that the new model captures
      the essential shear flow properties of real blood, except for capillaries of
      sizes comparable to the cell diameter. Finally, we investigate the influence of a
      geometrical constriction in the flow on the enhancement of the downstream CFL.
      Our results are in agreement with recent experiments.

PMID- 24282441
TI  - Structural changes in block copolymer micelles induced by cosolvent mixtures.
AB  - We investigated the influence of tetrahydrofuran (THF) addition on the structure
      of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution.
      Our studies showed that while the micelles remained starlike, the micelle core
      corona interfacial tension and micelle size decreased upon THF addition. The
      detailed effects of the reduction in interfacial tension were probed using
      contrast variations in small angle neutron scattering (SANS) experiments. At low
      THF contents (high interfacial tensions), the SANS data were fit to a micelle
      form factor that incorporated a radial density distribution of corona chains to
      account for the starlike micelle profile. However, at higher THF contents (low
      interfacial tensions), the presence of free chains in solution affected the
      scattering at high q and required the implementation of a linear combination of
      micelle and Gaussian coil form factors. These SANS data fits indicated that the
      reduction in interfacial tension led to broadening of the core-corona interface,
      which increased the PB chain solvent accessibility at intermediate THF solvent
      fractions. We also noted that the micelle cores swelled with increasing THF
      addition, suggesting that previous assumptions of the micelle core solvent
      content in cosolvent mixtures may not be accurate. Control over the size, corona
      thickness, and extent of solvent accessible PB in these micelles can be a
      powerful tool in the development of targeting delivery vehicles.

PMID- 24282442
TI  - Effectiveness of variable-gain Kalman filter based on angle error calculated from
      acceleration signals in lower limb angle measurement with inertial sensors.
AB  - The wearable sensor system developed by our group, which measured lower limb
      angles using Kalman-filtering-based method, was suggested to be useful in
      evaluation of gait function for rehabilitation support. However, it was expected
      to reduce variations of measurement errors. In this paper, a variable-Kalman-gain
      method based on angle error that was calculated from acceleration signals was
      proposed to improve measurement accuracy. The proposed method was tested
      comparing to fixed-gain Kalman filter and a variable-Kalman-gain method that was
      based on acceleration magnitude used in previous studies. First, in angle
      measurement in treadmill walking, the proposed method measured lower limb angles
      with the highest measurement accuracy and improved significantly foot inclination
      angle measurement, while it improved slightly shank and thigh inclination angles.
      The variable-gain method based on acceleration magnitude was not effective for
      our Kalman filter system. Then, in angle measurement of a rigid body model, it
      was shown that the proposed method had measurement accuracy similar to or higher
      than results seen in other studies that used markers of camera-based motion
      measurement system fixing on a rigid plate together with a sensor or on the
      sensor directly. The proposed method was found to be effective in angle
      measurement with inertial sensors. 

PMID- 24282443
TI  - Prior image guided undersampled dual energy reconstruction with piecewise
      polynomial function constraint.
AB  - Dual energy CT has the ability to give more information about the test object by
      reconstructing the attenuation factors under different energies. These images
      under different energies share identical structures but different attenuation
      factors. By referring to the fully sampled low-energy image, we show that it is
      possible to greatly reduce the sampling rate of the high-energy image in order to
      lower dose. To compensate the attenuation factor difference between the two
      modalities, we use piecewise polynomial fitting to fit the low-energy image to
      the high-energy image. During the reconstruction, the result is constrained by
      its distance to the fitted image, and the structural information thus can be
      preserved. An ASD-POCS-based optimization schedule is proposed to solve the
      problem, and numerical simulations are taken to verify the algorithm. 

PMID- 24282444
TI  - Pathologic improvement after high-dose melphalan and autologous stem cell
      transplantation for primary systemic amyloidosis.
AB  - Although primary systemic amyloid light-chain amyloidosis was considered
      intractable, recent advances in therapy have been reported to result in better
      clinical outcomes including remission of nephrotic syndrome. However, changes in
      renal pathologic findings after high-dose chemo- therapy have not been
      characterized. We describe a patient who underwent serial renal biopsies and had
      complete remission after high-dose melphalan and autologous stem cell
      transplantation for this form of amyloidosis. Successive renal biopsy specimens
      showed reduction in amyloid staining mainly in interlobular arterial and
      arteriolar walls. Thus, amyloid light-chain amyloidosis resolved both clinically
      and pathologically after high-dose chemotherapy.

PMID- 24282445
TI  - Imaging of auriculotemporal nerve perineural spread.
AB  - IMPORTANCE: Adenoid cystic carcinomas (ACCs) are relatively rare tumours,
      notorious for wide local infiltration and perineural spread. Perineural extension
      commonly occurs along branches of the trigeminal and facial nerves, and its
      presence represents a poor prognostic factor with implications for treatment
      approach. OBSERVATIONS: We report the case of a 61-year-old female presenting
      with worsening left facial numbness and weakness. On magnetic resonance imaging,
      the patient was found to have perineural spread of a left parotid tumour along
      the auriculotemporal nerve. There was involvement of the V2 and V3 branches of
      the trigeminal nerve. An ultrasound-guided biopsy of the mass demonstrated ACC.
      CONCLUSIONS AND RELEVANCE: The auriculotemporal nerve may serve as a route for
      tumour spread, particularly in the setting of head and neck malignancy. Moreover,
      this particular suspicion should be raised when patients with known malignancy
      experience concomitant trigeminal (V) and facial (VII) nerve dysfunctions.

PMID- 24282446
TI  - A case of chronic myeloid leukaemia presenting as megakaryocytic blast crisis
      (AML M7).
AB  - Acute megakaryocytic leukaemia (AMeL) is a rare subtype of acute myeloid
      leukaemia, which can be frequently misdiagnosed as acute myelofibrosis or
      myelosclerosis [1]. Chronic myeloid leukaemia (CML) presenting primarily as
      megakaryocytic blast crisis is very rare, with very few case reports published to
      date [2, 3]. This case report describes a 36-year-old woman who presented with
      anaemia and massive splenomegaly with peripheral blood and bone marrow showing
      features of AMeL. Reverse transcriptase polymerase chain reaction and gel
      electrophoretic study of peripheral blood leucocytes demonstrated breakpoint
      cluster region-Abelson oncogene translocation encoding for p210 fusion protein.
      Megakaryocytic blast crisis as the primary presentation of CML is very rare and
      requires clinical correlation and additional cytogenetic studies to determine the
      diagnosis. 

PMID- 24282447
TI  - Audio podcasts in practical courses in biochemistry - cost-efficient e-learning
      in a well-proven format from radio broadcasting.
AB  - INTRODUCTION: Audio podcasts are an e-learning format that may help to motivate
      students to deal with the contents of medical education more intensely. We
      adopted a well-proven format from radio broadcasting, the radio documentary, to
      direct the listeners' attention to information about practical courses in
      biochemistry over a period of 20 minutes at most. Information, original sounds,
      and a specific atmosphere allow listeners to perceive the contents intensely.
      METHOD: In order to organise the production of the podcast as cost-efficient and
      least time-consuming as possible, a student, a teacher, a clinician, and a
      technical assistant compile the core themes of their respective text blocks in an
      editorial conference first. After that, the speakers can elaborate on and record
      their blocks independently. Coordination is widely handled by the student. At two
      points of time, the podcasts were evaluated by the medical students by means of a
      questionnaire. RESULTS: With little cost and time expenses, eight podcasts were
      produced. They have been used by the students extensively and have also been
      evaluated very positively by non-student listeners. For long-term usage, a
      regular reference to the podcast offer is required in the courses. CONCLUSION:
      Involving students, successful podcasts can be produced to support classroom
      teaching with little expenses and contribute to the external presentation of the
      medical faculty.

PMID- 24282448
TI  - Predictors of a positive attitude of medical students towards general practice -
      a survey of three Bavarian medical faculties.
AB  - OBJECTIVE: Germany is witnessing an increasing shortage of general practitioners
      (GPs). The aim was to determine predictors of the job-related motivation of
      medical students of three medical faculties with different institutionalisation
      of general practice as an academic discipline. METHODS: Medical students were
      surveyed with a standardised questionnaire about their attitudes towards general
      practice and their motivation to work as a GP in different working conditions.
      Predictors for positive attitudes and motivation were calculated using logistic
      regression models. RESULTS: 940 (15.2%) out of 6182 medical students from three
      Bavarian medical faculties participated in an online survey. 585 (62.7%) were
      female, and the average age was 25.0 (standard deviation 3.7). The average grade
      of a university-entrance diploma was 1.6 (standard deviation 0.5). 718 (76.4%)
      could imagine working as a GP. However, they favoured being employed within
      another organisation and not having their own private practice (65.5% vs. 35.1%).
      "Presence of a professorship of general practice" was associated with a positive
      attitude towards general practice (OR 1.57; 95%CI 1.13-2.417). Motivation for
      working as a GP was associated with "being female" (OR 2.56; 95%CI 1.80-3.56) and
      "presence of a professorship of general practice" (OR 1.68; 95%CI 1.14-2.46).
      Having a lower grade for one's university-entrance diploma was associated with a
      higher preference to work in one's own practice (OR 1.39; 95%CI 1.02-1.90).
      CONCLUSION: A high amount of medical students were open-minded towards general
      practice. However, they favoured employment within an organization over working
      in their own practice. Institutionalisation of general practice as an academic
      discipline might be of importance to gain positive attitudes towards general
      practice and motivate medical students to work as a GP.

PMID- 24282449
TI  - The Hamburg selection procedure for dental students - introduction of the HAM-Nat
      as subject-specific test for study aptitude.
AB  - INTRODUCTION: The present study examines the question whether the selection of
      dental students should be based solely on average school-leaving grades (GPA) or
      whether it could be improved by using a subject-specific aptitude test. METHODS:
      The HAM-Nat Natural Sciences Test was piloted with freshmen during their first
      study week in 2006 and 2007. In 2009 and 2010 it was used in the dental student
      selection process. The sample size in the regression models varies between 32 and
      55 students. RESULTS: Used as a supplement to the German GPA, the HAM-Nat test
      explained up to 12% of the variance in preclinical examination performance. We
      confirmed the prognostic validity of GPA reported in earlier studies in some, but
      not all of the individual preclinical examination results. CONCLUSION: The HAM
      Nat test is a reliable selection tool for dental students. Use of the HAM-Nat
      yielded a significant improvement in prediction of preclinical academic success
      in dentistry.

PMID- 24282450
TI  - Entrustable professional activities - visualization of competencies in
      postgraduate training. Position paper of the Committee on Postgraduate Medical
      Training of the German Society for Medical Education (GMA).

PMID- 24282451
TI  - Suicidality among medical students - a practical guide for staff members in
      medical schools.
AB  - Although suicidality in medical students is important, few studies dealt with
      this issue regarding German universities. Our aims were to describe the
      epidemiology as well as factors leading to suicidality in medical students.
      Furthermore we wanted to raise awareness for this topic among university
      employees and show options for handling suicidal crises in students. This
      manuscript especially aims to address university employees working in direct
      contact with students (such as student counselors or teachers). 

PMID- 24282452
TI  - Training of leadership skills in medical education.
AB  - BACKGROUND: Effective team performance is essential in the delivery of high
      quality health-care. Leadership skills therefore are an important part of
      physicians' everyday clinical life. To date, the development of leadership skills
      are underrepresented in medical curricula. Appropriate training methods for
      equipping doctors with these leadership skills are highly desirable. OBJECTIVE:
      The review aims to summarize the findings in the current literature regarding
      training in leadership skills in medicine and tries to integrate the findings to
      guide future research and training development. METHOD: The PubMED, ERIC, and
      PsycArticles, PsycINFO, PSYNDEX and Academic search complete of EBSCOhost were
      searched for training of leadership skills in medicine in German and English.
      Relevant articles were identified and findings were integrated and consolidated
      regarding the leadership principles, target group of training and number of
      participants, temporal resources of the training, training content and methods,
      the evaluation design and trainings effects. RESULTS: Eight studies met all
      inclusion criteria and no exclusion criteria. The range of training programs is
      very broad and leadership skill components are diverse. Training designs implied
      theoretical reflections of leadership phenomena as well as discussions of case
      studies from practice. The duration of training ranged from several hours to
      years. Reactions of participants to trainings were positive, yet no behavioral
      changes through training were examined. CONCLUSIONS: More research is needed to
      understand the factors critical to success in the development of leadership
      skills in medical education and to adapt goal-oriented training methods.
      Requirements analysis might help to gain knowledge about the nature of leadership
      skills in medicine. The authors propose a stronger focus on behavioral training
      methods like simulation-based training for leadership skills in medical
      education.

PMID- 24282453
TI  - V-Loc urethro-intestinal anastomosis during robotic cystectomy with orthotopic
      urinary diversion.
AB  - INTRODUCTION: Robotic-assisted radical cystectomy (RARC) is an emerging minimally
      invasive alternative for the treatment of invasive bladder cancer. The V-loc
      (Covidien, Mansfield, MA) suture is a unidirectional barbed suture that provides
      even distribution of tension. We determined the rate of urinary leak at the
      urethro-intestinal anastomosis following orthotopic neobladder construction
      performed with V-loc suture. METHODS: We retrospectively reviewed charts on all
      patients that underwent RARC with orthotopic neobladder urinary diversion
      performed with a V-loc suture from February 2010 to February 2012. The urethro
      intestinal anastomosis was evaluated for urinary leak by cystogram at 3 to 4
      weeks, postoperatively. RESULTS: In total, 11 patients were available for
      analysis. The mean patient age was 57.2 years (range: 47-71). The average
      clinical follow-up was 8 months (range: 4-15). On surgical pathology, 8 (73%)
      patients had pT2 or less disease, 3 (27%) had pT3/T4 disease, and 1 (9%) had N+
      disease. The mean intraoperative blood loss was 315 mL (range: 150-600) and the
      average operative time was 496 minutes (range: 485-519). No patient (0%)
      demonstrated a urinary leak at the urethro-intestinal anastomosis on
      postoperative cystogram. Eight patients (73%) were continent by 4 months,
      postoperatively. CONCLUSIONS: Orthotopic neobladder urethro-intestinal
      anastomosis can be performed effectively and safely with V-loc suture with an
      acceptably low urinary leak rate.

PMID- 24282454
TI  - Regional differences in practice patterns and outcomes in patients treated with
      radical cystectomy in a universal healthcare system.
AB  - INTRODUCTION: Our objective is to assess differences in practice patterns and
      outcomes across 3 regions in bladder cancer patients treated with radical
      cystectomy under a universal healthcare system. METHODS: In total, we included
      2287 patients treated with radical cystectomy at 8 Canadian centres from 1998 to
      2008. Variables included various clinico-pathologic parameters, recurrence, and
      death stratified into different regions. RESULTS: In total, 1105 patients were
      from the east region (group 1), 601 from the centre region (group 2), and 581
      from the west region of Canada (group 3). The median follow-up of groups 1, 2,
      and 3 was 22.1, 17.1, and 28.6 months, respectively. Although the overall rate of
      neoadjuvant chemotherapy was low (3.1%), rates were higher in group 2 compared
      with groups 1 and 3 (p = 0.07). Continent diversions and extended lymphadenectomy
      were performed in 23.5%, 8.5%, 23.9% and 39.7%, 27.7%, 12.6% across groups 1, 2,
      and 3, respectively. There were statistically significant differences in gender
      distribution, performance of lymphadenectomy, presence of concomitant carcinoma
      in situ and lymphovascular invasion across the 3 groups. There were no
      differences among the 3 geographical locations in terms of stage, surgical margin
      status, and use of adjuvant chemotherapy. The mean number of days from the
      transurethral resection of the bladder tumour to cystectomy was 50, 79, 69 days
      for groups 1, 2, 3, respectively (p = 0.0006). The 5-year overall survival was
      53.6%, 66.8%, and 52.4% for groups 1, 2 and 3, respectively (p < 0.0001).
      CONCLUSIONS: Significant variations in practice patterns were noted across
      different geographic regions in a universal healthcare system. Use of continent
      diversions, extended lymphadenectomy, and neoadjuvant chemotherapy remains low
      across all 3 regions. Treatment delays are significant.

PMID- 24282455
TI  - The comparison of laparoscopy, shock wave lithotripsy and retrograde intrarenal
      surgery for large proximal ureteral stones.
AB  - INTRODUCTION: In this study we compare the success rates and complication rates
      of shock wave lithotripsy (SWL), laparoscopic, and ureteroscopic approaches for
      large (between 1 and 2 cm) proximal ureteral stones. METHODS: In total, 151
      patients with ureteral stones between 1 and 2 cm in diameter were randomized into
      3 groups (52 SWL, 51 laparoscopy and 48 retrograde intrarenal surgery [RIRS]).
      The groups were compared for stone size, success rates, and complication rates
      using the modified Clavien grading system. RESULTS: Stone burden of the groups
      were similar (p = 0.36). The success rates were 96%, 81% and 79%, respectively in
      the laparoscopy, SWL, and ureteroscopy groups. The success rate in laparoscopy
      group was significantly higher (p < 0.05). When these groups were compared for
      complication rates, RIRS seemed to be the group with the lowest complication
      rates (4.11%) (p < 0.05). SWL and laparoscopy seem to have similar rates of
      complication (7.06% and 7.86%, respectively, p = 0.12). INTERPRETATION: To our
      knowledge, this is the first study to compare the results of laparoscopy, SWL and
      RIRS in ureteral stones. Our results showed that in management of patients with
      upper ureteral stones between 1 and 2 cm, laparoscopy is the most successful
      method based on its stone-free rates and acceptable complication rates. However,
      the limitations of our study are lack of hospital stay and cost-effectiveness
      data. Also, studies conducted on larger populations should support our findings.
      When a less invasive method is the only choice, SWL and flexible ureterorenoscopy
      methods have similar success rates. RIRS, however, has a lower complication rate
      than the other approaches.

PMID- 24282456
TI  - Can the Hounsfield unit predict the success of medically expulsive therapy?
AB  - BACKGROUND: We investigate the predictability of medical expulsive therapy (MET)
      success with alpha blockers based on Hounsfield unit (HU) values and Hounsfield
      density (HD) values measured by computed tomography (CT) for distal ureteral
      stones. METHODS: Between July 2011 and May 2012, 44 patients (19 female and 25
      male) with 5- to 10-mm stones in the distal ureters were included in this
      randomized prospective study. Non-contrast CT examinations were performed in
      these patients. HU and HD values of stones were calculated. Doxazosine, 4 mg/day
      orally, was administered as a single dose to all patients for MET. RESULTS:
      Patients were divided into 2 groups. Group 1 included 18 patients (43.9%) with
      dropped stones with MET. Group 2 included 23 patients (56.1%) with no stone
      passage with MET. In Group 1, the mean stone size was 7.7 mm, the mean HU was
      507, and the HD was 53.04/mm. In Group 2, the mean stone size was 8.25 mm, the
      mean HU was 625, and the mean HD was 61.54/mm. The HU and HD values in Group 2
      were higher than in Group 1. However, there was no statistically significant
      difference (p = 0.85 and 0.93 for HU and HD, respectively). INTERPRETATION: We
      found that HU and HD values cannot be used to predict the chances of success for
      MET. Although the sample size is appropriate for the study, further comparative
      studies involving more patients are warranted.

PMID- 24282457
TI  - Effects of low-frequency ultrasound combined with microbubbles on benign prostate
      hyperplasia.
AB  - INTRODUCTION: Our objective is to assess the effects of low-frequency ultrasound
      combined with microbubbles on benign prostate hyperplasia (BPH). METHODS: Sixteen
      Beagle dogs with BPH were randomly assigned into 4 groups (n = 4): control group
      (without treatment), G1 group (injection with 2 mL of microbubble contrast
      agent); G2 group (21 kHz ultrasound); and G3 group (injection with 2 mL of micro
      bubble contrast agent +21 kHz ultrasound). The histopathological damage to
      prostate cells was assessed via transmission electron microscopy and optical
      microscopy. The protein expressions of prostate-specific antigen (PSA), inducible
      nitric oxide synthase (iNOS), superoxide dismutase (SOD) of vessels were detected
      by enzyme-linked immunosorbent assay (ELISA). RESULTS: Histopathologically, the
      prostate cells exhibited nuclear chromatin contraction, mitochondrial swelling,
      degranulation of rough endoplasmic reticulum, basement membrane rupture and cell
      apoptosis in the G2 and G3 groups; it was especially obvious in the G3 group,
      while no changes were observed in the control and G1 groups. Although prostate
      volume using imaging was not significantly changed in all groups after treatment,
      PSA was significantly reduced in the G2 and G3 groups, and especially obvious in
      the G3 group (p < 0.05). The iNOS and SOD, which are important oxidative stress
      factors, significantly increased after treatment in the G2 and G3 groups, but not
      in the control and G1 groups (p < 0.05). CONCLUSIONS: Low-frequency ultrasound is
      effective in treating BPH; low-frequency ultrasound combined with microbubbles
      improves the treatment efficacy.

PMID- 24282458
TI  - The impact of metformin use on recurrence and cancer-specific survival in
      clinically localized high-risk renal cell carcinoma.
AB  - BACKGROUND: Recent data suggest that metformin may have anti-neoplastic
      properties. We sought to determine what effect metformin had on recurrence and
      cancer-specific survival (CSS) rates of patients with clinically localized pT2
      and pT3 renal cell carcinoma (RCC) following radical or partial nephrectomy.
      METHODS: We obtained data on 784 patients who underwent partial or radical
      nephrectomy for pT2 or pT3 tumours at our centre between 1996 and 2011. Patients
      with benign masses, nodal positivity, or metastasis at the time of surgery were
      excluded. Using a competing-risks regression model, we compared differences in
      probability of recurrence between patients who used metformin versus those who
      did not. RESULTS: The patients on metformin at the time of surgery had worse
      disease recurrence than patients not on metformin. However, this was not
      statistically significant on multivariate analysis when controlling for age,
      race, body mass index, glomerular filtration rate, and tumour stage and grade
      (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.66-2.27 [p = 0.5]).
      Metformin use was associated with a lower risk of cancer-specific mortality, but
      this was not statistically significant when adjusted for clinical and tumour
      characteristics (HR, 0.76; 95% CI 0.21-2.7 [p = 0.7]). Limitations include the
      retrospective nature of the study and the lack on information on duration of
      metformin use. CONCLUSIONS: Metformin use at the time of surgery for high-risk
      clinically localized RCC is not protective in terms of recurrence or CSS. Further
      studies should be done to confirm these findings and determine what effect
      concurrent metformin use might have on improved response to targeted therapies in
      the metastatic setting.

PMID- 24282459
TI  - Exercise effects on adipokines and the IGF axis in men with prostate cancer
      treated with androgen deprivation: A randomized study.
AB  - BACKGROUND: Androgen deprivation therapy (ADT) has significant deleterious
      effects on body composition that may be accompanied by unfavourable changes in
      adipokine levels. While exercise has been shown to improve a number of side
      effects associated with ADT for prostate cancer, no studies have assessed the
      effect of exercise on adiponectin and leptin levels, which have been shown to
      alter the mitogenic environment. METHODS: Twenty-six men with prostate cancer
      treated with ADT were randomized to home-based aerobic exercise training or
      resistance exercise training for 24 weeks. Adiponectin, leptin, insulin-like
      growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3)
      were analyzed by ELISA (enzyme-linked immunosorbent assay), in addition to
      physical activity volume, peak aerobic capacity, and anthropometric measurements,
      at baseline, 3 months and 6 months. RESULTS: Resistance exercise significantly
      reduced IGF-1 after 3 months (p = 0.019); however, this change was not maintained
      at 6 months. At 6 months, IGFBP-3 was significantly increased compared to
      baseline for the resistance training group (p = 0.044). In an exploratory
      analysis of all exercisers, favourable changes in body composition and aerobic
      fitness were correlated with favourable levels of leptin, and favourable
      leptin:adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months. CONCLUSIONS: Home
      based exercise is correlated with positive changes in adipokine levels and the
      IGF-axis that may be related to healthy changes in physical fitness and body
      composition. While the improvements of adipokine markers appear to be more
      apparent with resistance training compared to aerobic exercise, these findings
      must be considered cautiously and require replication from larger randomized
      controlled trials to clarify the role of exercise on adipokines and IGF-axis
      proteins for men with prostate cancer.

PMID- 24282460
TI  - Can 3T multiparametric magnetic resonance imaging accurately detect prostate
      cancer extracapsular extension?
AB  - BACKGROUND: Accurate staging is essential to determine the correct management of
      patients diagnosed with prostate cancer. We assess the accuracy of 3T
      multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI)
      in detecting prostate cancer local extension. METHODS: We retrospectively
      reviewed charts from January 2008 to July 2012 from all patients undergoing
      radical prostatectomy. Patients were only included if 3TemMRI and radical
      prostatectomy were performed at our institution. Based on the presence of
      extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into
      locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging
      was then evaluated using definitive pathology as a reference. RESULTS: Overall,
      177 radical prostatectomies were performed within the timeframe. After applying
      exclusion criteria, 60 patients were included in the final analysis. The mean
      patient age was 67 +/- 7 (standard deviation) years. Mean prostate-specific
      antigen value was 12.7 +/- 12.7 ng/L. Based on preoperative characteristics, we
      considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an
      organ-confined tumour in 46 patients and locally advanced disease in 14 patients.
      When correlated to final pathology, 3TemMRI specificity, sensitivity, negative
      and positive predictive values, and accuracy in detecting locally advanced
      prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively. INTERPRETATION:
      This study shows that the use of preoperative 3TemMRI can be used to identify
      organ-confined prostate cancer when locally advanced disease is suspected.

PMID- 24282461
TI  - The effects of cigarette smoking on prostate-specific antigen in two different
      age groups.
AB  - BACKGROUND: We investigate the effects of cigarette smoking on prostate-specific
      antigen (PSA) using 2 different age groups. METHODS: The study was carried out
      between January 2007 and October 2011 with men; the 2 sets of age groups were: 25
      to 35 years and 50 to 70 years old. The participants were divided into 4 groups.
      Of the 25 to 35 age range, smokers were Group 1, and non-smokers were Group 2; of
      the 50 to 70 age range, smokers were Group 3 and non-smokers Group 4. In
      addition, for the 50 to 70 age group, the International Prostate Symptom Score
      was completed, digital rectal examination was performed, and transabdominal
      prostate volume was measured. We wanted to see whether prostate-specific antigen
      (PSA) levels showed a difference between the 2 age groups. RESULTS: There were
      114 patients in Group 1, 82 in Group 2, 90 in Group 3, and 102 in Group 4. The
      mean PSA level was 0.7 +/- 0.28 ng/mL for Group 1, and 0.6 +/- 0.27 ng/mL for
      Group 2 (p = 0.27), and there was no statistically significant difference between
      the 2 groups. The mean PSA was 2.5 +/- 1.8 ng/mL for Group 3, and 2.1 +/- 2.0
      ng/mL (p = 0.59) for Group 4, and there was no statistically significant
      difference between the these 2 age groups. INTERPRETATION: Cigarette smoking
      effects various hormone levels. Different from previous studies, the PSA level
      was higher in smokers compared to nonsmokers, although it was not statistically
      significant. Our study is limited by the small numbers in our study groups and
      the lack of PSA velocity data.

PMID- 24282462
TI  - Clinical character of cystitis glandularis accompanied with upper urinary tract
      obstruction.
AB  - OBJECTIVE: We explore the clinical character of cystitis glandularis accompanied
      with upper urinary tract obstruction. METHODS: We compared 70 cases of cystitis
      glandularis accompanied with upper urinary tract obstruction with 60 cases of
      cystitis glandularis without upper urinary tract obstruction. The difference of
      clinical manifestation and surgical efficacy was observed between the 2 groups.
      RESULTS: The incidence of cystitis glandularis in women was higher than in men
      and the age of patients with cystitis glandularis and upper urinary tract
      obstruction was younger than the age of patients without upper urinary tract
      obstruction. The main symptom of cystitis glandularis accompanied with upper
      urinary tract obstruction were renal colic and abdominal pain; a few patients
      with a shorter course of the disease also had nausea, vomiting, frequency,
      urgency, dysuria, hematuria and fever. The distribution and morphological
      characteristics of lesions on the bladder and in the urine culture were not
      different between the 2 groups. There was no second operation on patients with
      upper urinary tract obstruction, but at least a second operation was performed on
      9.3% patients without upper urinary tract obstruction. CONCLUSIONS: In patients
      with upper urinary tract obstruction, we found that it was the main clinical
      symptom of their cystitis glandularis. Identifying and removing the causes of
      upper urinary tract obstruction is the most important management method. For the
      cystitis glandularis, active treatment or close follow-up should be made.

PMID- 24282463
TI  - Achieving proficiency with robot-assisted radical prostatectomy: Laparoscopic
      trained versus robotics-trained surgeons.
AB  - BACKGROUND: Initiating a robotics program is complex, in regards to achieving
      favourable outcomes, effectively utilizing an expensive surgical tool, and
      granting console privileges to surgeons. We report the implementation of a
      community-based robotics program among minimally-invasive surgery (MIS)
      urologists with and without formal robotics training. METHODS: From August 2008
      to December 2010 at Kaiser Permanente Southern California, 2 groups of urologists
      performing robot-assisted radical prostatectomy (RARP) were followed since the
      time of robot acquisition at a single institution. The robotics group included 4
      surgeons with formal robotics training and the laparoscopic group with another 4
      surgeons who were robot-naive, but skilled in laparoscopy. The laparoscopic group
      underwent an initial 7-day mentorship period. Surgical proficiency was measured
      by various operative and pathological outcome variables. Data were evaluated
      using comparative statistics and multivariate analysis. RESULTS: A total of 420
      and 549 RARPs were performed by the robotics and laparoscopic groups,
      respectively. Operative times were longer in the laparoscopic group (p = 0.002),
      but estimated blood loss was similar. The robotics group had a significantly
      better overall positive surgical margin rate of 19.9% compared to the
      laparoscopic group (27.8%) (p = 0.005). Both groups showed improvements in
      operative and pathological parameters as they accrued experience, and achieved
      similar results towards the end of the study. CONCLUSIONS: Robot-naive
      laparoscopic surgeons may achieve similar outcomes to robotic surgeons relatively
      early after a graduated mentorship period. This study may apply to a community
      based practice in which multiple urologists with varied training backgrounds are
      granted robot privileges.

PMID- 24282464
TI  - A population-based study on the association between urinary calculi and kidney
      cancer.
AB  - BACKGROUND: Using a nationwide population-based dataset and case-control study
      design, we investigate the association between urinary calculi (UC) and kidney
      cancer (KC) in Taiwan. METHODS: The data for this case-control study were sourced
      from the Taiwan National Health Insurance program. The cases included 1308
      incident patients pathologically diagnosed with KC. This study also used 6540
      randomly selected subjects as controls. Conditional logistic regression was used
      to examine the associations between KC and patients previously diagnosed with UC.
      RESULTS: Of the sampled patients, 1262 (16.1 %) had previously been diagnosed
      with UC; 415 (31.7 % of the patients with KC) and 847 controls (13.0 % of
      patients without KC). After adjusting for monthly income, geographic location,
      urbanization level, hypertension, diabetes, renal disease, obesity, cystic kidney
      disease, tobacco use disorder, and alcohol abuse, we found that patients with KC
      were likely to have been previously diagnosed with UC than controls (odds ratio
      [OR] 3.18, 95% confidence interval [CI] 2.75-3.68, p < 0.001). In addition, the
      magnitude of the observed associations were stronger among females (females OR
      3.59; 95% CI 2.87-4.48 vs. males OR 2.93, 95% CI 2.42-3.55) and transitional cell
      carcinoma patients (transitional cell carcinoma, OR 3.96; 95% CI 3.23-4.86 vs.
      renal cell carcinoma OR 2.76, 95% CI 2.31-3.29). CONCLUSIONS: We conclude that
      there is an association between KC and prior UC, especially in females and
      patients with transitional cell carcinoma.

PMID- 24282465
TI  - The role of PSA density to predict a pathological tumour upgrade between needle
      biopsy and radical prostatectomy for low risk clinical prostate cancer in the
      modified Gleason system era.
AB  - OBJECTIVES: We evaluate the role of prostate-specific antigen (PSA) density to
      predict Gleason score upgrade between prostate biopsy material and radical
      prostatectomy specimen examination in patients with low-risk prostate cancer.
      METHODS: Between January 2007 and November 2011, 133 low-risk patients underwent
      a radical prostatectomy. Using the modified Gleason criteria, tumour grade of the
      surgical specimens was examined and compared to the biopsy results. RESULTS: A
      tumour upgrade was noticed in 57 (42.9%) patients. Organ-confined disease was
      found in 110 (82.7%) patients, while extracapsular disease and seminal vesicles
      invasion was found in 19 (14.3%) and 4 (3.0%) patients, respectively. Positive
      surgical margins were reported in 23 (17.3%) patients. A statistical significant
      correlation between the preoperative PSA density value and postoperative upgrade
      was found (p = 0.001) and this observation had a predictive value (p = 0.002);
      this is in contrast to the other studied parameters which failed to reach
      significance, including PSA, percentage of cancer in biopsy and number of biopsy
      cores. Tumour upgrade was also highly associated with extracapsular cancer
      extension (p = 0.017) and the presence of positive surgical margins (p = 0.017).
      CONCLUSIONS: PSA density represents a strong predictor for Gleason score upgrade
      after radical prostatectomy in patients with clinical low-risk disease. Since
      tumour upgrade increases the potential for postoperative pathological adverse
      findings and prognosis, PSA density should be considered when treating and
      consulting patients with low-risk prostate cancer.

PMID- 24282466
TI  - Endoscopic treatment of ureterovesical junction obstructive pathology: A
      description of the oblique meatotomy technique and results.
AB  - BACKGROUND: Benign obstructive pathology of the ureterovesical junction includes
      congenital and acquired illnesses. The objective of this study was to describe
      the endoscopic oblique meatotomy technique using scissors and cold cutting to
      treat benign obstructive pathology of the ureterovesical junction. METHODS: From
      2007 to 2012, we treated 18 patients with obstructive pathology of the
      ureterovesical junction (5 megaureters [3 with lithiasis], 4 iatrogenic stenoses,
      and 9 ureteroceles with lithiasis). In all cases, oblique meatotomy was performed
      using endoscopic scissors through an 8.5 Ch ureteroscope. The mean follow-up for
      all patients was 3 years. Pain, grade of hydronephrosis, and occurrence of
      vesicoureteral reflux were evaluated before and after treatment. RESULTS: The
      mean endoscopic treatment time was 13.4 minutes. The procedure was performed on
      an outpatient basis with 6 hours of hospital admission, and a double J stent was
      inserted for 6 weeks. We achieved treatment success in 94.5% of patients after 3
      years of follow-up. Only 1 patient presented with vesicoureteral reflux at 12
      months after treatment; however, this condition did not require further
      treatment. Overall, 100% of patients remained free from lithiasis. There are 2
      main limitations: the small number of patients and the lack of another group to
      compare the results of this technique; however, the aim of this work was to
      communicate a new technique to treat ureterovesical junction stricture.
      INTERPRETATION: Oblique ureteral meatotomy is a safe and effective treatment for
      benign obstructive pathology of the ureterovesical junction and has a low index
      of complications.

PMID- 24282467
TI  - Variations in prostate biopsy practice: A quantitative questionnaire-based study.
AB  - BACKGROUND: The ambivalent results of recent large randomized prostate cancer
      studies have added a significant layer of uncertainty for clinicians and patients
      contemplating investigation of early disease. This uncertainty and lack of
      prescriptive recommendations from professional organizations has led to
      significant variation in practice in North America. The purpose of this study was
      to determine the extent of variation in biopsy recommendations by urologists and
      to discern factors predictive for these recommendations. METHODS: An anonymous,
      cross-sectional, self-report questionnaire was sent to all active members of the
      Canadian Urological Association practicing in Ontario. The survey consisted of
      demographic data and 10 closed-ended questions designed to capture biopsy
      preferences in ambiguous clinical situations. Respondent preferences for
      recommending a prostate biopsy were compared to a guideline-informed study
      standard. Descriptive and correlative statistics were used to analyze the
      responses. RESULTS: The response rate to the survey was 74%. The responses showed
      considerable variability in recommendations for or against biopsy. While most of
      the urologists concurred with the research team's study standard recommendations,
      only 4 scenarios had over 80% concurrence and 1 scenario, which centered on the
      utility of free PSA, had only had 42% concurrence. None of the respondent's
      descriptors were associated with trends to recommend biopsy other than the number
      of biopsies performed per year (p = 0.04). INTERPRETATION: This self-report
      survey investigating prostate biopsy thresholds identifies considerable variation
      in practicing urologists in Ontario. The drivers of biopsy recommendations in
      these relatively ambiguous clinical situations appeared to be age, suspicious
      rectal examinations, and total PSA.

PMID- 24282468
TI  - Effect of anticoagulants and antiplatelet agents on the efficacy of intravesical
      BCG treatment of bladder cancer: A systematic review.
AB  - We performed a systematic review of publications describing a correlation between
      oral anticoagulant medications and intravesical BCG outcome. We collected
      information on the impact of such medications on tumour recurrence and
      progression and we excluded papers not reporting outcome correlations. Patients
      were divided into group 1 and 2 based on whether they were taking or not taking
      any anticoagulant medications. A total of 7 manuscripts published between 1990
      and 2009 were included in this study. Data heterogeneity precluded meta-analysis.
      In studies combining all anticoagulant medications, 3 out of 5 (60%) publications
      did not identify any difference in outcome, while 2 (40%) documented
      significantly more recurrences in group 1 patients. In studies performing
      multivariate analysis and only examining the intake of 1 medication, warfarin
      alone seemed to be associated with increased risk of bladder tumour recurrences
      and progression following intravesical BCG treatment, while ASA alone seemed to
      be associated with more protective effects. There is no strong evidence to
      support the allegations of a protective role of ASA and a deleterious role for
      warfarin. Further, well-designed experimental and clinical studies are needed to
      clarify the mechanism of action of intravesical BCG along with possible drug
      interactions. 

PMID- 24282469
TI  - Alpha-fetoprotein and carbohydrate antigen 19-9 producing advanced adenocarcinoma
      of renal pelvis and ureter.
AB  - Tumour markers producing primary adenocarcinoma of upper urinary tract is
      extremely rare. We report a case of advanced adenocarcinoma of renal pelvis and
      ureter with highly elevated serum levels of alpha-fetoprotein (AFP) and
      carbohydrate antigen 19-9 (CA19-9). This 66-year-old man was diagnosed with left
      renal pelvic and ureteral tumours with para-aortic lymph node swelling, with no
      evidence of abnormality in his digestive or reproductive system. He was
      successfully treated with left nephroureterectomy and lymph node dissection
      followed by gemcitabine/carboplatin chemotherapy and the serum levels of AFP and
      CA19-9 decreased to normal. Pathological examination revealed a moderately or
      poorly differentiated intestinal-type adenocarcinoma with para-aortic lymph node
      metastasis. The patient was followed up for 11 months after surgery without
      recurrence. 

PMID- 24282470
TI  - Emphysematous cystitis: The role of CT imaging and appropriate treatment.
AB  - Emphysematous cystitis is a relatively rare disease characterized by the presence
      of gas in the bladder wall and/or lumen. The primary risk factor is diabetes
      mellitus. Emphysematous cystitis should be considered in cases of urinary tract
      infections in diabetic patients with unusual presentations. Imaging studies are
      necessary to detect emphysematous cystitis. Accurate diagnosis of the disease and
      appropriate treatment typically results in a favourable prognosis and can improve
      the outcome. We present a case of emphysematous cystitis diagnosed by a computed
      tomography scan in a diabetic woman with poor glycemic control. 

PMID- 24282471
TI  - Prolapsed cecoureterocele presented as a prenatal genital mass: A urological
      challenge.
AB  - Prolapse of a cecoureterocele through the urethra presenting as a prenatal vulval
      mass is an extremely uncommon entity. We present a case of a newborn girl with a
      cecoureterocele extending through the urethra (diagnosed at 29 weeks' gestation)
      and we present its postnatal findings and outcomes. 

PMID- 24282472
TI  - Complications following breast cancer therapy in the adult spina bifida
      population: A case report.
AB  - Survival to adulthood in spina bifida has greatly increased with the advent of
      modern therapies. With this prolonging of life expectancy, patients are exposed
      to the risk of adult onset malignancies and the complications of subsequent
      treatment. We present the case of a 66-year-old woman born with a terminal
      lipomyelomeningocele, presenting with new fecal incontinence and a desire to
      undivert her ileal conduit. The deterioration was attributed to chemotherapy for
      breast cancer. We highlight the urologic challenges of breast cancer management
      in the neurogenic bowel population, as well as the utility of an adult spina
      bifida clinic. To the best of our knowledge, this is the first case report of a
      spina bifida patient presenting with fecal and urinary complications from breast
      cancer chemotherapy. 

PMID- 24282473
TI  - Localized amyloidosis of the ureter: A case report and literature review.
AB  - Localized amyloidosis of the ureter is a rare disease and can easily be confused
      with a neoplasm. We report the case of a 55-year-old woman who presented with
      loin pain and painless gross hematuria. We also reviewed the English literature
      about localized ureteral amyloidosis. Middle-aged women were likely to suffer
      from this disorder. Loin pain and hematuria were the main clinical features.
      There were no specific performance on radiologic imaging and ureteral
      calcification was not widespread. Compared to upper ureter and middle ureter, the
      lower ureter was the easiest involved part. Nephroureterectomy was the
      predominant treatment. Biopsies via a ureteroscope prior to surgery or
      intraoperative frozen section examination, which yielded the diagnosis of
      amyloidosis, could help to avoid unnecessary surgery. The use of dimethyl
      sulfoxide or follow-up with serial imaging may become a promising treatment. 

PMID- 24282474
TI  - Primary signet ring cell carcinoma of the prostate.
AB  - A 61-year-old Korean man was referred to our institution because of high prostate
      specific antigen (PSA) (8.1ng/mL) and frequency, nocturia that had lasted for the
      previous 4 months. The first transrectal ultrasonography (TRUS)-guided prostate
      biopsy result was benign prostatic hyperplasia. About 3 years later, the patients
      revisited our institute for elevated PSA (14.7 ng/mL) and back pain. The patient
      underwent a second TRUS-guided prostate biopsy. Histological examination and
      immunohistochemical staining showed a signet ring cell carcinoma (SRCC). Also
      there were multiple bony metastasis. Androgen deprivation therapy (ADT) was
      started. Nine months later, the patient was diagnosed with hormone refractory
      prostate cancer and the ADT was changed into docetaxel chemotherapy. The patient
      died after 2 cycles of chemotherapy. We report this case of a SRCC of the
      prostate and review the literature. 

PMID- 24282475
TI  - Supernumerary kidney laparoscopically treated.
AB  - Congenital anomalies of the kidney and urinary tract are part of a family of
      diseases with different anatomical origins. Duplicated collecting systems can be
      defined as a renal unit containing 2 pyelocalyceal systems associated with a
      single ureter or with double ureters. The supernumerary kidney is a definitive
      accessory organ with its own collecting system, blood supply, and distinct
      encapsulated parenchima. The true incidence of supernumerary kidney remains
      unknown, but most cases are in males, are unilateral and on the left side. We
      present a case of an adult woman with a hypoplastic supernumerary kidney with a
      complete ureteral duplication and an ectopic junction. The case has been
      laparoscopically treated. We demonstrate that a laparoscopic nephro-ureterectomy
      is feasible and that the management of the complication (urinoma and fistula) can
      be managed conservatively. 

PMID- 24282476
TI  - [Not Available].

PMID- 24282477
TI  - A comparison of blue light and caffeine effects on cognitive function and
      alertness in humans.
AB  - The alerting effects of both caffeine and short wavelength (blue) light have been
      consistently reported. The ability of blue light to enhance alertness and
      cognitive function via non-image forming neuropathways have been suggested as a
      non-pharmacological countermeasure for drowsiness across a range of occupational
      settings. Here we compare and contrast the alerting and psychomotor effects of
      240 mg of caffeine and a 1-h dose of ~40 lx blue light in a non-athletic
      population. Twenty-one healthy subjects performed a computer-based psychomotor
      vigilance test before and after each of four randomly assigned trial conditions
      performed on different days: white light/placebo; white light/240 mg caffeine;
      blue light/placebo; blue light/240 mg caffeine. The Karolinska Sleepiness Scale
      was used to assess subjective measures of alertness. Both the caffeine only and
      blue light only conditions enhanced accuracy in a visual reaction test requiring
      a decision and an additive effect was observed with respect to the fastest
      reaction times. However, in a test of executive function, where a distraction was
      included, caffeine exerted a negative effect on accuracy. Furthermore, the blue
      light only condition consistently outperformed caffeine when both congruent and
      incongruent distractions were presented. The visual reactions in the absence of a
      decision or distraction were also enhanced in the blue light only condition and
      this effect was most prominent in the blue-eyed participants. Overall, blue light
      and caffeine demonstrated distinct effects on aspects of psychomotor function and
      have the potential to positively influence a range of settings where cognitive
      function and alertness are important. Specifically, despite the widespread use of
      caffeine in competitive sporting environments, the possible impact of blue light
      has received no research attention. 

PMID- 24282478
TI  - An efficient strategy for small-scale screening and production of archaeal
      membrane transport proteins in Escherichia coli.
AB  - BACKGROUND: Membrane proteins play a key role in many fundamental cellular
      processes such as transport of nutrients, sensing of environmental signals and
      energy transduction, and account for over 50% of all known drug targets. Despite
      their importance, structural and functional characterisation of membrane proteins
      still remains a challenge, partially due to the difficulties in recombinant
      expression and purification. Therefore the need for development of efficient
      methods for heterologous production is essential. METHODOLOGY/PRINCIPAL FINDINGS:
      Fifteen integral membrane transport proteins from Archaea were selected as test
      targets, chosen to represent two superfamilies widespread in all organisms known
      as the Major Facilitator Superfamily (MFS) and the 5-Helix Inverted Repeat
      Transporter superfamily (5HIRT). These proteins typically have eleven to twelve
      predicted transmembrane helices and are putative transporters for sugar,
      metabolite, nucleobase, vitamin or neurotransmitter. They include a wide range of
      examples from the following families: Metabolite-H(+)-symporter; Sugar Porter;
      Nucleobase-Cation-Symporter-1; Nucleobase-Cation-Symporter-2; and
      neurotransmitter-sodium-symporter. Overproduction of transporters was evaluated
      with three vectors (pTTQ18, pET52b, pWarf) and two Escherichia coli strains (BL21
      Star and C43 (DE3)). Thirteen transporter genes were successfully expressed; only
      two did not express in any of the tested vector-strain combinations. Initial
      trials showed that seven transporters could be purified and six of these yielded
      quantities of >= 0.4 mg per litre suitable for functional and structural studies.
      Size-exclusion chromatography confirmed that two purified transporters were
      almost homogeneous while four others were shown to be non-aggregating, indicating
      that they are ready for up-scale production and crystallisation trials.
      CONCLUSIONS/SIGNIFICANCE: Here, we describe an efficient strategy for
      heterologous production of membrane transport proteins in E. coli. Small-volume
      cultures (10 mL) produced sufficient amount of proteins to assess their purity
      and aggregation state. The methods described in this work are simple to implement
      and can be easily applied to many more membrane proteins.

PMID- 24282479
TI  - Cervicothoracic multisegmental transpinal evoked potentials in humans.
AB  - The objectives of this study were to establish the neurophysiological properties
      of the transpinal evoked potentials (TEPs) following transcutaneous electric
      stimulation of the spine (tsESS) over the cervicothoracic region, changes in the
      amplitude of the TEPs preceded by median nerve stimulation at group I threshold,
      and the effects of tsESS on the flexor carpi radialis (FCR) H-reflex in thirteen
      healthy human subjects while seated. Two re-usable self-adhering electrodes,
      connected to function as one electrode (cathode), were placed bilaterally on the
      clavicles. A re-usable electrode (anode) was placed on the cervicothoracic region
      covering from Cervical 4-Thoracic 2 and held under constant pressure throughout
      the experiment. TEPs were recorded bilaterally from major arm muscles with
      subjects seated at stimulation frequencies of 1.0, 0.5, 0.33, 0.2, 0.125, and 0.1
      Hz, and upon double tsESS pulses delivered at an inter-stimulus interval of 40
      ms. TEPs from the arm muscles were also recorded following median nerve
      stimulation at the conditioning-test (C-T) intervals of 2, 3, 5, 8, and 10 ms.
      The FCR H-reflex was evoked and recorded according to conventional methods
      following double median nerve pulses at 40 ms, and was also conditioned by tsESS
      at C-T intervals that ranged from -10 to +50 ms. The arm TEPs amplitude was not
      decreased at low-stimulation frequencies and upon double tsESS pulses in all but
      one subject. Ipsilateral and contralateral arm TEPs were facilitated following
      ipsilateral median nerve stimulation, while the FCR H-reflex was depressed by
      double pulses and following tsESS at short and long C-T intervals. Non-invasive
      transpinal stimulation can be used as a therapeutic modality to decrease spinal
      reflex hyper-excitability in neurological disorders and when combined with
      peripheral nerve stimulation to potentiate spinal output.

PMID- 24282480
TI  - Local NMDA receptor blockade attenuates chronic tinnitus and associated brain
      activity in an animal model.
AB  - Chronic tinnitus has no broadly effective treatment. Identification of specific
      markers for tinnitus should facilitate the development of effective therapeutics.
      Recently it was shown that glutamatergic blockade in the cerebellar
      paraflocculus, using an antagonist cocktail was successful in reducing chronic
      tinnitus. The present experiment examined the effect of selective N-methyl d
      aspartate (NMDA) receptor blockade on tinnitus and associated spontaneous brain
      activity in a rat model. The NMDA antagonist, D(-)-2-amino-5-phosphonopentanoic
      acid (D-AP5) (0.5 mM), was continuously infused for 2 weeks directly to the
      ipsilateral paraflocculus of rats with tinnitus induced months prior by
      unilateral noise exposure. Treated rats were compared to untreated normal
      controls without tinnitus, and to untreated positive controls with tinnitus. D
      AP5 significantly decreased tinnitus within three days of beginning treatment,
      and continued to significantly reduce tinnitus throughout the course of treatment
      and for 23 days thereafter, at which time testing was halted. At the conclusion
      of psychophysical testing, neural activity was assessed using manganese enhanced
      magnetic resonance imaging (MEMRI). In agreement with previous research,
      untreated animals with chronic tinnitus showed significantly elevated bilateral
      activity in their paraflocculus and brainstem cochlear nuclei, but not in mid or
      forebrain structures. In contrast, D-AP5-treated-tinnitus animals showed
      significantly less bilateral parafloccular and dorsal cochlear nucleus activity,
      as well as significantly less contralateral ventral cochlear nucleus activity. It
      was concluded that NMDA-mediated glutamatergic transmission in the paraflocculus
      appears to be a necessary component of chronic noise-induced tinnitus in a rat
      model. Additionally, it was confirmed that in this model, elevated spontaneous
      activity in the cerebellar paraflocculus and auditory brainstem is associated
      with tinnitus. 

PMID- 24282481
TI  - Serum ceruloplasmin levels correlate negatively with liver fibrosis in males with
      chronic hepatitis B: a new noninvasive model for predicting liver fibrosis in HBV
      related liver disease.
AB  - AIMS: This study aimed to investigate associations between ceruloplasmin (CP)
      levels, inflammation grade and fibrosis stages in patients with chronic hepatitis
      B (CHB) and to establish a noninvasive model to predict cirrhosis. METHODS: Liver
      biopsy samples and sera were collected from 198 CHB patients randomized into a
      training group (n=109) and a validation group (n=89). CP levels were determined
      using nephelometric immunoassays. Relationships between CP and liver inflammation
      and fibrosis were analyzed by Spearman rank correlation. Receiver operator
      characteristic (ROC) curves were used to evaluate the diagnostic value of CP for
      determining liver fibrosis in CHB. The liver pathology-predictive model was built
      using multivariate logistic regression analysis to identify relevant indicators.
      RESULTS: CP levels were lower in males than in females, lower in patients with
      inflammation stage G4 compared to other stages and lower in cirrhotic compared to
      non-cirrhotic patients. Using area under the curve (AUC) values, CP levels
      distinguished different stages of inflammation and fibrosis. Multivariate
      analysis showed that CP levels were all significantly associated with cirrhosis
      in males. A model was developed combining routine laboratory markers APPCI (alpha
      fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict
      fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4
      (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI
      (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl
      transpeptidase [GGT]) models (all P-values<0.001). CONCLUSIONS: CP levels
      correlate negatively and indirectly with inflammation and fibrosis stages in male
      CHB patients. The APPCI model uses routine laboratory variables with CP to
      accurately predict liver fibrosis in CHB.

PMID- 24282482
TI  - Cataract, visual impairment and long-term mortality in a rural cohort in India:
      the Andhra Pradesh Eye Disease Study.
AB  - BACKGROUND: A large-scale prevalence survey of blindness and visual impairment
      (The Andhra Pradesh Eye Diseases Study [APEDS1]) was conducted between 1996-2000
      on 10,293 individuals of all ages in three rural and one urban clusters in Andhra
      Pradesh, Southern India. More than a decade later (June 2009-March 2010), APEDS1
      participants in rural clusters were traced (termed APEDS2) to determine ocular
      risk factors for mortality in this longitudinal cohort. METHODS AND FINDINGS:
      Mortality hazard ratio (HR) analysis was performed for those aged >30 years at
      APEDS1, using Cox proportional hazard regression models to identify associations
      between ocular exposures and risk of mortality. Blindness and visual impairment
      (VI) were defined using Indian definitions. 799/4,188 (19.1%) participants had
      died and 308 (7.3%) had migrated. Mortality was higher in males than females
      (p<0.001). In multivariable analysis, after adjusting for age, gender, diabetes,
      hypertension, body mass index, smoking and education status the mortality HR was
      1.9 (95% CI: 1.5-2.5) for blindness; 1.4 (95% CI: 1.2-1.7) for VI; 1.8 (95% CI:
      1.4-2.3) for pure nuclear cataract, 1.5 (95% CI: 1.1-2.1) for pure cortical
      cataract; 1.96 (95% CI: 1.6-2.4) for mixed cataract, 2.0 (95% CI: 1.4-2.9) for
      history of cataract surgery, and 1.58 (95% CI: 1.3-1.9) for any cataract. When
      all these factors were included in the model, the HRs were attenuated, being 1.5
      (95% CI: 1.1-2.0) for blindness and 1.2 (95% CI: 0.9-1.5) for VI. For lens type,
      the HRs were as follows: pure nuclear cataract, 1.6 (95% CI: 1.3-2.1); pure
      cortical cataract, 1.5 (95% CI: 1.1-2.1); mixed cataract, 1.8 (95% CI: 1.4-2.2),
      and history of previous cataract surgery, 1.8 (95% CI: 1.3-2.6). CONCLUSIONS: All
      types of cataract, history of cataract surgery and VI had an increased risk of
      mortality that further suggests that these could be potential markers of ageing.

PMID- 24282495
TI  - Randomised controlled trial of joint crisis plans to reduce compulsory treatment
      for people with psychosis: economic outcomes.
AB  - BACKGROUND: Compulsory admission to psychiatric hospitals may be distressing,
      disruptive to patients and families, and associated with considerable cost to the
      health service. Improved patient experience and cost reductions could be realised
      by providing cost-effective crisis planning services. METHODS: Economic
      evaluation within a multi-centre randomised controlled trial comparing Joint
      Crisis Plans (JCP) plus treatment as usual (TAU) to TAU alone for patients aged
      over 16, with at least one psychiatric hospital admission in the previous two
      years and on the Enhanced Care Programme Approach register. JCPs, containing the
      patient's treatment preferences for any future psychiatric emergency, are a form
      of crisis intervention that aim to mitigate the negative consequences of relapse,
      including hospital admission and use of coercion. Data were collected at baseline
      and 18-months after randomisation. The primary outcome was admission to hospital
      under the Mental Health Act. The economic evaluation took a service perspective
      (health, social care and criminal justice services) and a societal perspective
      (additionally including criminal activity and productivity losses). FINDINGS: The
      addition of JCPs to TAU had no significant effect on compulsory admissions or
      total societal cost per participant over 18-months follow-up. From the service
      cost perspective, however, evidence suggests a higher probability (80%) of JCPs
      being the more cost-effective option. Exploration by ethnic group highlights
      distinct patterns of costs and effects. Whilst the evidence does not support the
      cost-effectiveness of JCPs for White or Asian ethnic groups, there is at least a
      90% probability of the JCP intervention being the more cost-effective option in
      the Black ethnic group. INTERPRETATION: The results by ethnic group are
      sufficiently striking to warrant further investigation into the potential for
      patient gain from JCPs among black patient groups. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN11501328.

PMID- 24282496
TI  - A proteomic investigation of soluble olfactory proteins in Anopheles gambiae.
AB  - Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are small
      soluble polypeptides that bind semiochemicals in the lymph of insect
      chemosensilla. In the genome of Anopheles gambiae, 66 genes encode OBPs and 8
      encode CSPs. Here we monitored their expression through classical proteomics (2D
      gel-MS analysis) and a shotgun approach. The latter method proved much more
      sensitive and therefore more suitable for tiny biological samples as mosquitoes
      antennae and eggs. Females express a larger number and higher quantities of OBPs
      in their antennae than males (24 vs 19). OBP9 is the most abundant in the
      antennae of both sexes, as well as in larvae, pupae and eggs. Of the 8 CSPs, 4
      were detected in antennae, while SAP3 was the only one expressed in larvae. Our
      proteomic results are in fairly good agreement with data of RNA expression
      reported in the literature, except for OBP4 and OBP5, that we could not identify
      in our analysis, nor could we detect in Western Blot experiments. The relatively
      limited number of soluble olfactory proteins expressed at relatively high levels
      in mosquitoes makes further studies on the coding of chemical messages at the OBP
      level more accessible, providing for few specific targets. Identification of such
      proteins in Anopheles gambiae might facilitate future studies on host finding
      behavior in this important disease vector. 

PMID- 24282497
TI  - Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP.
      Alteration of this signal in Mdx mice is a likely cause of dystrophy.
AB  - ATP signaling has been shown to regulate gene expression in skeletal muscle and
      to be altered in models of muscular dystrophy. We have previously shown that in
      normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after
      electrical stimulation plays a role in activating some signaling pathways related
      to gene expression. We searched for a possible role of ATP signaling in the
      dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated
      from normal and mdx mice. We demonstrated that low frequency electrical
      stimulation has an anti-apoptotic effect in normal muscle fibers repressing the
      expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a
      similar effect. In dystrophic fibers, the basal levels of extracellular ATP were
      higher compared to normal fibers, but unlike control fibers, they do not present
      any ATP release after low frequency electrical stimulation, suggesting an
      uncoupling between electrical stimulation and ATP release in this condition.
      Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine
      receptors) were found in triads fractions prepared from mdx muscles. Moreover,
      decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the
      signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro
      apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the
      levels of activated Bax and cytosolic cytochrome c. These evidence points to an
      involvement of the ATP pathway in the activation of mechanisms related with cell
      death in muscular dystrophy, opening new perspectives towards possible targets
      for pharmacological therapies. 

PMID- 24282498
TI  - Prevalence and characteristics of probable major depression and bipolar disorder
      within UK biobank: cross-sectional study of 172,751 participants.
AB  - OBJECTIVES: UK Biobank is a landmark cohort of over 500,000 participants which
      will be used to investigate genetic and non-genetic risk factors for a wide range
      of adverse health outcomes. This is the first study to systematically assess the
      prevalence and validity of proposed criteria for probable mood disorders within
      the cohort (major depression and bipolar disorder). METHODS: This was a
      descriptive epidemiological study of 172,751 individuals assessed for a lifetime
      history of mood disorder in relation to a range of demographic, social,
      lifestyle, personality and health-related factors. The main outcomes were
      prevalence of a probable lifetime (single) episode of major depression, probable
      recurrent major depressive disorder (moderate), probable recurrent major
      depressive disorder (severe), probable bipolar disorder and no history of mood
      disorder (comparison group). Outcomes were compared on age, gender, ethnicity,
      socioeconomic status, educational attainment, functioning, self-reported health
      status, current depressive symptoms, neuroticism score, smoking status and
      alcohol use. RESULTS: Prevalence rates for probable single lifetime episode of
      major depression (6.4%), probable recurrent major depression (moderate) (12.2%),
      probable recurrent major depression (severe) (7.2%) and probable bipolar disorder
      (1.3%) were comparable to those found in other population studies. The proposed
      diagnostic criteria have promising validity, with a gradient in evidence from no
      mood disorder through major depression and probable bipolar disorder in terms of
      gender distribution, socioeconomic status, self-reported health rating, current
      depressive symptoms and smoking. SIGNIFICANCE: The validity of our proposed
      criteria for probable major depression and probable bipolar disorder within this
      cohort are supported by these cross-sectional analyses. Our findings are likely
      to prove useful as a framework for a wide range of future genetic and non-genetic
      studies.

PMID- 24282499
TI  - Differential effects of the catechol-O-methyltransferase Val158Met genotype on
      the cognitive function of schizophrenia patients and healthy Japanese
      individuals.
AB  - BACKGROUND: The functional polymorphism Val158Met in the catechol-O
      methyltransferase (COMT) gene has been associated with differences in prefrontal
      cognitive functions in patients with schizophrenia and healthy individuals.
      Several studies have indicated that the Met allele is associated with better
      performance on measures of cognitive function. We investigated whether the COMT
      Val158Met genotype was associated with cognitive function in 149 healthy controls
      and 118 patients with schizophrenia. METHODS: Cognitive function, including
      verbal memory, working memory, motor speed, attention, executive function and
      verbal fluency, was assessed by the Brief Assessment of Cognition in
      Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a
      multiple regression analysis to determine the associations between the COMT
      Val158Met genotype and the BACS-J measurements. RESULTS: The one-way ANOVA
      revealed a significant difference in the scores on the Tower of London, a measure
      of executive function, between the different Val158Met genotypes in the healthy
      controls (p = 0.023), and a post-hoc analysis showed significant differences
      between the scores on the Tower of London in the val/val genotype group (18.6 +/-
      2.4) compared to the other two groups (17.6 +/- 2.7 for val/met and 17.1 +/- 3.2
      for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses
      revealed that executive function was significantly correlated with the Val158Met
      genotype (p = 0.003). However, no evidence was found for an effect of the COMT on
      any cognitive domains of the BACS-J in the patients with schizophrenia.
      CONCLUSION: These data support the hypothesis that the COMT Val158Met genotype
      maintains an optimal level of dopamine activity. Further studies should be
      performed that include a larger sample size and include patients on and off
      medication, as these patients would help to confirm our findings.

PMID- 24282500
TI  - Circulating MicroRNAs in maternal blood as potential biomarkers for fetal hypoxia
      in-utero.
AB  - Stillbirth affects 1 in 200 pregnancies and commonly arises due to a lack of
      oxygen supply to the fetus. Current tests to detect fetal hypoxia in-utero lack
      the sensitivity to identify many babies at risk. Emerging evidence suggests that
      microRNAs derived from the placenta circulate in the maternal blood during
      pregnancy and may serve as non-invasive biomarkers for pregnancy complications.
      In this study, we examined the expression of miRs known to be regulated by
      hypoxia in two clinical settings of significant fetal hypoxia: 1) labour and 2)
      fetal growth restriction. Six miRs (miR 210, miR 21, miR 424, miR 199a, miR 20b,
      and miR 373) were differentially expressed in pregnancies complicated by fetal
      hypoxia. In healthy term pregnancies there was a 4.2 fold increase in miR 210
      (p<0.01), 2.7 fold increase in miR 424 (p<0.05), 2.6 fold increase in miR 199a
      (p<0.01) and 2.3 fold increase in miR 20b (p<0.05) from prior to labour to
      delivery of the fetus. Furthermore, the combined expression of miR 21 and miR 20b
      correlated with the degree of fetal hypoxia at birth determined by umbilical cord
      lactate delivery (r = 0.79, p = 0.03). In pregnancies complicated by severe
      preterm fetal growth restriction there was upregulation of the hypoxia-regulated
      miRs compared to gestation-matched controls: 3.6 fold in miR 210 (p<0.01), 3.6
      fold in miR 424 (p<0.05), 5.9 fold in miR 21 (p<0.01), 3.8 fold in miR 199a
      (p<0.01) and 3.7 fold in miR 20b (p<0.01). Interestingly, the expression of miR
      373 in gestation matched controls was very low, but was very highly expressed in
      FGR (p<0.0001). Furthermore, the expression increased in keeping with the degree
      of in-utero hypoxia estimated by fetal Doppler velocimetry. We conclude
      quantifying hypoxia-regulated miRs in the maternal blood may identify pregnancies
      at risk of fetal hypoxia, enabling early intervention to improve perinatal
      outcomes.

PMID- 24282501
TI  - A machine learning approach to automated structural network analysis: application
      to neonatal encephalopathy.
AB  - Neonatal encephalopathy represents a heterogeneous group of conditions associated
      with life-long developmental disabilities and neurological deficits. Clinical
      measures and current anatomic brain imaging remain inadequate predictors of
      outcome in children with neonatal encephalopathy. Some studies have suggested
      that brain development and, therefore, brain connectivity may be altered in the
      subgroup of patients who subsequently go on to develop clinically significant
      neurological abnormalities. Large-scale structural brain connectivity networks
      constructed using diffusion tractography have been posited to reflect
      organizational differences in white matter architecture at the mesoscale, and
      thus offer a unique tool for characterizing brain development in patients with
      neonatal encephalopathy. In this manuscript we use diffusion tractography to
      construct structural networks for a cohort of patients with neonatal
      encephalopathy. We systematically map these networks to a high-dimensional space
      and then apply standard machine learning algorithms to predict neurological
      outcome in the cohort. Using nested cross-validation we demonstrate high
      prediction accuracy that is both statistically significant and robust over a
      broad range of thresholds. Our algorithm offers a novel tool to evaluate neonates
      at risk for developing neurological deficit. The described approach can be
      applied to any brain pathology that affects structural connectivity. 

PMID- 24282502
TI  - Do diagnosis delays impact receipt of test results? Evidence from the HIV early
      infant diagnosis program in Uganda.
AB  - BACKGROUND: There is scant evidence on the association between diagnosis delays
      and the receipt of test results in HIV Early Infant Diagnosis (EID) programs. We
      determine the association between diagnosis delays and other health care system
      and patient factors on result receipt. METHODS: We reviewed 703 infant HIV test
      records for tests performed between January 2008 and February 2009 at a regional
      referral hospital and level four health center in Uganda. The main outcome was
      caregiver receipt of the test result. The primary study variable was turnaround
      time (time between sample collection and result availability at the health
      facility). Additional variables included clinic entry point, infant age at sample
      collection, reported HIV status and receipt of antiretroviral prophylaxis for
      prevention of mother-to-child transmission. We conducted a pooled analysis in
      addition to separate analyses for each facility. We estimated the relative risk
      of result receipt using modified Poisson regression with robust standard errors.
      RESULTS: Overall, the median result turnaround time, was 38 days. 59% of
      caregivers received infant test results. Caregivers were less likely to receive
      results at turnaround times greater than 49 days compared to 28 days or fewer
      (ARR = 0.83; 95% CI = 0.70-0.98). Caregivers were more likely to receive results
      at the PMTCT clinic (ARR = 1.81; 95% CI = 1.40-2.33) and less likely at the
      pediatric ward (ARR = 0.54; 95% CI = 0.37-0.81) compared to the immunization
      clinic. At the level four health center, result receipt was half as likely among
      infants older than 9 months compared to 3 months and younger (ARR= 0.47; 95% CI =
      0.25-0.93). CONCLUSION: In this study setting, we find evidence that longer
      turnaround times, clinic entry point and age at sample collection may be
      associated with receipt of infant HIV test results.

PMID- 24282503
TI  - SVD identifies transcript length distribution functions from DNA microarray data
      and reveals evolutionary forces globally affecting GBM metabolism.
AB  - To search for evolutionary forces that might act upon transcript length, we use
      the singular value decomposition (SVD) to identify the length distribution
      functions of sets and subsets of human and yeast transcripts from profiles of
      mRNA abundance levels across gel electrophoresis migration distances that were
      previously measured by DNA microarrays. We show that the SVD identifies the
      transcript length distribution functions as "asymmetric generalized coherent
      states" from the DNA microarray data and with no a-priori assumptions. Comparing
      subsets of human and yeast transcripts of the same gene ontology annotations, we
      find that in both disparate eukaryotes, transcripts involved in protein synthesis
      or mitochondrial metabolism are significantly shorter than typical, and in
      particular, significantly shorter than those involved in glucose metabolism.
      Comparing the subsets of human transcripts that are overexpressed in glioblastoma
      multiforme (GBM) or normal brain tissue samples from The Cancer Genome Atlas, we
      find that GBM maintains normal brain overexpression of significantly short
      transcripts, enriched in transcripts that are involved in protein synthesis or
      mitochondrial metabolism, but suppresses normal overexpression of significantly
      longer transcripts, enriched in transcripts that are involved in glucose
      metabolism and brain activity. These global relations among transcript length,
      cellular metabolism and tumor development suggest a previously unrecognized
      physical mode for tumor and normal cells to differentially regulate metabolism in
      a transcript length-dependent manner. The identified distribution functions
      support a previous hypothesis from mathematical modeling of evolutionary forces
      that act upon transcript length in the manner of the restoring force of the
      harmonic oscillator. 

PMID- 24282504
TI  - Controllability in cancer metabolic networks according to drug targets as driver
      nodes.
AB  - Networks are employed to represent many nonlinear complex systems in the real
      world. The topological aspects and relationships between the structure and
      function of biological networks have been widely studied in the past few decades.
      However dynamic and control features of complex networks have not been widely
      researched, in comparison to topological network features. In this study, we
      explore the relationship between network controllability, topological parameters,
      and network medicine (metabolic drug targets). Considering the assumption that
      targets of approved anticancer metabolic drugs are driver nodes (which control
      cancer metabolic networks), we have applied topological analysis to genome-scale
      metabolic models of 15 normal and corresponding cancer cell types. The results
      show that besides primary network parameters, more complex network metrics such
      as motifs and clusters may also be appropriate for controlling the systems
      providing the controllability relationship between topological parameters and
      drug targets. Consequently, this study reveals the possibilities of following a
      set of driver nodes in network clusters instead of considering them individually
      according to their centralities. This outcome suggests considering distributed
      control systems instead of nodal control for cancer metabolic networks, leading
      to a new strategy in the field of network medicine. 

PMID- 24282505
TI  - Deep genetic divergence between disjunct Refugia in the Arctic-Alpine King's
      Crown, Rhodiola integrifolia (Crassulaceae).
AB  - Despite the strength of climatic variability at high latitudes and upper
      elevations, we still do not fully understand how plants in North America that are
      distributed between Arctic and alpine areas responded to the environmental
      changes of the Quaternary. To address this question, we set out to resolve the
      evolutionary history of the King's Crown, Rhodiola integrifolia using multi-locus
      population genetic and phylogenetic analyses in combination with ecological niche
      modeling. Our population genetic analyses of multiple anonymous nuclear loci
      revealed two major clades within R. integrifolia that diverged from each other ~
      700 kya: one occurring in Beringia to the north (including members of subspecies
      leedyi and part of subspecies integrifolia), and the other restricted to the
      Southern Rocky Mountain refugium in the south (including individuals of
      subspecies neomexicana and part of subspecies integrifolia). Ecological niche
      models corroborate our hypothesized locations of refugial areas inferred from our
      phylogeographic analyses and revealed some environmental differences between the
      regions inhabited by its two subclades. Our study underscores the role of
      geographic isolation in promoting genetic divergence and the evolution of endemic
      subspecies in R. integrifolia. Furthermore, our phylogenetic analyses of the
      plastid spacer region trnL-F demonstrate that among the native North American
      species, R. integrifolia and R. rhodantha are more closely related to one another
      than either is to R. rosea. An understanding of these historic processes lies at
      the heart of making informed management decisions regarding this and other Arctic
      alpine species of concern in this increasingly threatened biome. 

PMID- 24282506
TI  - Collective instance-level gene normalization on the IGN corpus.
AB  - A high proportion of life science researches are gene-oriented, in which
      scientists aim to investigate the roles that genes play in biological processes,
      and their involvement in biological mechanisms. As a result, gene names and their
      related information turn out to be one of the main objects of interest in
      biomedical literatures. While the capability of recognizing gene mentions has
      made significant progress, the results of recognition are still insufficient for
      direct use due to the ambiguity of gene names. Gene normalization (GN) goes
      beyond the recognition task by linking a gene mention to a database ID. Unlike
      most previous works, we approach GN on the instance-level and evaluate its
      overall performance on the recognition and normalization steps in abstracts and
      full texts. We release the first instance-level gene normalization (IGN) corpus
      in the BioC format, which includes annotations for the boundaries of all gene
      mentions and the corresponding IDs for human gene mentions. Species information,
      along with existing co-reference chains and full name/abbreviation pairs are also
      provided for each gene mention. Using the released corpus, we have designed a
      collective instance-level GN approach using not only the contextual information
      of each individual instance, but also the relations among instances and the
      inherent characteristics of full-text sections. Our experimental results show
      that our collective approach can achieve an F-score of 0.743. The proposed
      approach that exploits section characteristics in full-text articles can improve
      the F-scores of information lacking sections by up to 1.8%. In addition, using
      the proposed refinement process improved the F-score of gene mention recognition
      by 0.125 and that of GN by 0.03. Whereas current experimental results are limited
      to the human species, we seek to continue updating the annotations of the IGN
      corpus and observe how the proposed approach can be extended to other species. 

PMID- 24282507
TI  - New antimalarial hits from Dacryodes edulis (Burseraceae)--part I: isolation, in
      vitro activity, in silico "drug-likeness" and pharmacokinetic profiles.
AB  - The aims of the present study were to identify the compounds responsible for the
      anti-malarial activity of Dacryoedes edulis (Burseraceae) and to investigate
      their suitability as leads for the treatment of drug resistant malaria. Five
      compounds were isolated from ethyl acetate and hexane extracts of D. edulis stem
      bark and tested against 3D7 (chloroquine-susceptible) and Dd2 (multidrug
      resistant) strains of Plasmodium falciparum, using the parasite lactate
      dehydrogenase method. Cytotoxicity studies were carried out on LLC-MK2 monkey
      kidney epithelial cell-line. In silico analysis was conducted by calculating
      molecular descriptors using the MOE software running on a Linux workstation. The
      "drug-likeness" of the isolated compounds was assessed using Lipinski criteria,
      from computed molecular properties of the geometry optimized structures. Computed
      descriptors often used to predict absorption, distribution, metabolism,
      elimination and toxicity (ADMET) were used to assess the pharmacokinetic profiles
      of the isolated compounds. Antiplasmodial activity was demonstrated for the first
      time in five major natural products previously identified in D. edulis, but not
      tested against malaria parasites. The most active compound identified was termed
      DES4. It had IC50 values of 0.37 and 0.55 ug/mL, against 3D7 and Dd2
      respectively. In addition, this compound was shown to act in synergy with
      quinine, satisfied all criteria of "Drug-likeness" and showed considerable
      probability of providing an antimalarial lead. The remaining four compounds also
      showed antiplasmodial activity, but were less effective than DES4. None of the
      tested compounds was cytotoxicity against LLC-MK2 cells, suggesting their
      selective activities on malaria parasites. Based on the high in vitro activity,
      low toxicity and predicted "Drug-likeness" DES4 merits further investigation as a
      possible drug lead for the treatment of malaria. 

PMID- 24282508
TI  - Associations between family-related factors, breakfast consumption and BMI among
      10- to 12-year-old European children: the cross-sectional ENERGY-study.
AB  - OBJECTIVE: To investigate associations of family-related factors with children's
      breakfast consumption and BMI-z-score and to examine whether children's breakfast
      consumption mediates associations between family-related factors and children's
      BMI-z-score. SUBJECTS: Ten- to twelve-year-old children (n = 6374; mean age =
      11.6 +/- 0.7 years, 53.2% girls, mean BMI-z-score = 0.4 +/- 1.2) and one of their
      parents (n = 6374; mean age = 41.4 +/- 5.3 years, 82.7% female, mean BMI = 24.5
      +/- 4.2 kg/m(2)) were recruited from schools in eight European countries
      (Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia, Spain, and
      Switzerland). The children self-reported their breakfast frequency per week. The
      body weight and height of the children were objectively measured. The parents
      responded to items on family factors related to breakfast (automaticity,
      availability, encouragement, paying attention, permissiveness, negotiating,
      communicating health beliefs, parental self-efficacy to address children's
      nagging, praising, and family breakfast frequency). Mediation analyses were
      performed using multi-level regression analyses (child-school-country). RESULTS:
      Three of the eleven family-related variables were significantly associated with
      children's BMI-z-score. The family breakfast frequency was negatively associated
      with the BMI-z-score; permissiveness concerning skipping breakfast and
      negotiating about breakfast were positively associated with the BMI-z-score.
      Children's breakfast consumption was found to be a mediator of the two
      associations. All family-related variables except for negotiating, praising and
      communicating health beliefs, were significantly associated with children's
      breakfast consumption. CONCLUSIONS: Future breakfast promotion and obesity
      prevention interventions should focus on family-related factors including the
      physical home environment and parenting practices. Nevertheless, more
      longitudinal research and intervention studies to support these findings between
      family-related factors and both children's breakfast consumption and BMI-z-score
      are needed.

PMID- 24282509
TI  - Molecular cloning and characterisation of a novel type of human papillomavirus
      160 isolated from a flat wart of an immunocompetent patient.
AB  - More than 150 types of Human papillomaviruses (HPVs) have been isolated from
      numerous cutaneous and/or mucosal lesions. Flat wart samples on the face from 36
      immunocompetent patients were collected and screened for HPV. From one sample, we
      cloned a putative novel genotype. The novel type consisted of 7779 bp in length
      with a GC content of 47.1%, containing open reading frames for putative early
      proteins (E1, E2, E4, E6, and E7) and two late proteins (L1 and L2). Homology
      searches and phylogenetic analyses indicated that it belonged to
      Alphapapillomavirus (Alpha-PV) species 2 and most closely resembled HPV 3. The
      virus fulfilled the definition of a novel type, and was named HPV 160 by the
      Reference Center for Papillomaviruses. The putative E7 protein of HPV 160 as well
      as HPV 29, 77, and 78 contained the Leu-X-Cys-X-Glu pRB-binding motif but other
      Alpha-PV species 2 (HPV 3, 10, 28, 94, 117, and 125) did not have this conserved
      motif. 

PMID- 24282510
TI  - Pharmacokinetics of drugs in cachectic patients: a systematic review.
AB  - Cachexia is a weight-loss process caused by an underlying chronic disease such as
      cancer, chronic heart failure, chronic obstructive pulmonary disease, or
      rheumatoid arthritis. It leads to changes in body structure and function that may
      influence the pharmacokinetics of drugs. Changes in gut function and decreased
      subcutaneous tissue may influence the absorption of orally and transdermally
      applied drugs. Altered body composition and plasma protein concentration may
      affect drug distribution. Changes in the expression and function of metabolic
      enzymes could influence the metabolism of drugs, and their renal excretion could
      be affected by possible reduction in kidney function. Because no general
      guidelines exist for drug dose adjustments in cachectic patients, we conducted a
      systematic search to identify articles that investigated the pharmacokinetics of
      drugs in cachectic patients. 

PMID- 24282511
TI  - Cost-effectiveness of one year dementia follow-up care by memory clinics or
      general practitioners: economic evaluation of a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of post-diagnosis dementia
      treatment and coordination of care by memory clinics compared to general
      practitioners' care. METHODS: A multicentre randomised trial with 175 community
      dwelling patients newly diagnosed with mild to moderate dementia, and their
      informal caregivers, with twelve months' follow-up. Cost-effectiveness was
      evaluated from a societal point of view and presented as incremental cost per
      quality adjusted life year. To establish cost-effectiveness, a cost-utility
      analysis was conducted using utilities based on the EQ-5D. Uncertainty
      surrounding the incremental cost-effectiveness ratio (difference in costs divided
      by difference in effects) was calculated by bootstrapping from the original data.
      RESULTS: Compared to general practitioners' care, treatment by the memory clinics
      was on average ?1024 (95% CI: -?7723 to ?5674) cheaper, and showed a non
      significant decrease of 0.025 (95% CI: -0.114 to 0.064) quality adjusted life
      years. The incremental cost-effectiveness point estimate from the bootstrap
      simulation was ? 41 442 per QALY lost if one would use memory clinic care instead
      of general practitioner care. CONCLUSION: No evidence was found that memory
      clinics were more cost-effective compared to general practitioners with regard to
      post-diagnosis treatment and coordination of care of patients with dementia in
      the first year after diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00554047.

PMID- 24282512
TI  - Phenotypic and functional characterization of lymphocytes from different age
      groups of Bolivian squirrel monkeys (Saimiri boliviensis boliviensis).
AB  - Due to many physiological and genetic characteristic similarities to humans,
      squirrel monkeys provide an ideal animal model specifically for studying malaria,
      and transmissible spongiform encephalopathies (Creutzfeldt-Jacob disease). While
      squirrel monkeys three years and older are generally considered adult subjects
      suitable for use in medical research studies, little is known about the
      functional properties of lymphocytes in relation to the age of these animals,
      which could significantly impact the quality and quantity of innate and adaptive
      immune responses. In this study, we investigated differences in the phenotype and
      function of lymphocytes subsets of young (3-4 years), adult (8-10 years) and aged
      (16-19 years) squirrel monkeys. In general, animals in all three age groups
      exhibited comparable numbers of different lymphocyte subsets except for CD20+ B
      cells that were significantly lower in aged relative to young animals and T cells
      subsets expressing both CD4 and CD8 (double positive) were significantly higher
      in aged relative to young animals. With increasing age, phenotypic differences in
      central and effector memory T cells subsets were observed, that were more
      pronounced for the CD8+ T cells. Despite equal proportions of CD3+ T cells among
      the three age groups, responses of peripheral blood mononuclear cells to T cell
      mitogens PHA and Con A showed lower IFN-gamma producing cells in the aged group
      than that in the young group. Furthermore, aged animals showed significantly
      higher plasma levels of inflammatory cytokines IL-6, IFN-gamma, TNF-alpha, IL-10
      and IL-12. These findings suggest that while the squirrel monkeys in general
      share phenotypic and functional similarities of lymphocyte subsets with humans in
      relation to age, specific differences exist in immune function of lymphocytes
      between young and old animals that could potentially impact experimental outcomes
      for which the measurement of immunologic endpoints are critical. 

PMID- 24282513
TI  - Parameter estimation methods for chaotic intercellular networks.
AB  - We have investigated simulation-based techniques for parameter estimation in
      chaotic intercellular networks. The proposed methodology combines a
      synchronization-based framework for parameter estimation in coupled chaotic
      systems with some state-of-the-art computational inference methods borrowed from
      the field of computational statistics. The first method is a stochastic
      optimization algorithm, known as accelerated random search method, and the other
      two techniques are based on approximate Bayesian computation. The latter is a
      general methodology for non-parametric inference that can be applied to
      practically any system of interest. The first method based on approximate
      Bayesian computation is a Markov Chain Monte Carlo scheme that generates a series
      of random parameter realizations for which a low synchronization error is
      guaranteed. We show that accurate parameter estimates can be obtained by
      averaging over these realizations. The second ABC-based technique is a Sequential
      Monte Carlo scheme. The algorithm generates a sequence of "populations", i.e.,
      sets of randomly generated parameter values, where the members of a certain
      population attain a synchronization error that is lesser than the error attained
      by members of the previous population. Again, we show that accurate estimates can
      be obtained by averaging over the parameter values in the last population of the
      sequence. We have analysed how effective these methods are from a computational
      perspective. For the numerical simulations we have considered a network that
      consists of two modified repressilators with identical parameters, coupled by the
      fast diffusion of the autoinducer across the cell membranes. 

PMID- 24282514
TI  - Building a DNA barcode reference library for the true butterflies (Lepidoptera)
      of Peninsula Malaysia: what about the subspecies?
AB  - The objective of this study was to build a DNA barcode reference library for the
      true butterflies of Peninsula Malaysia and assess the value of attaching
      subspecies names to DNA barcode records. A new DNA barcode library was
      constructed with butterflies from the Museum of Zoology, University of Malaya
      collection. The library was analysed in conjunction with publicly available DNA
      barcodes from other Asia-Pacific localities to test the ability of the DNA
      barcodes to discriminate species and subspecies. Analyses confirmed the capacity
      of the new DNA barcode reference library to distinguish the vast majority of
      species (92%) and revealed that most subspecies possessed unique DNA barcodes
      (84%). In some cases conspecific subspecies exhibited genetic distances between
      their DNA barcodes that are typically seen between species, and these were often
      taxa that have previously been regarded as full species. Subspecies designations
      as shorthand for geographically and morphologically differentiated groups provide
      a useful heuristic for assessing how such groups correlate with clustering
      patterns of DNA barcodes, especially as the number of DNA barcodes per species in
      reference libraries increases. Our study demonstrates the value in attaching
      subspecies names to DNA barcode records as they can reveal a history of taxonomic
      concepts and expose important units of biodiversity. 

PMID- 24282515
TI  - Interactions between snow chemistry, mercury inputs and microbial population
      dynamics in an Arctic snowpack.
AB  - We investigated the interactions between snowpack chemistry, mercury (Hg)
      contamination and microbial community structure and function in Arctic snow.
      Snowpack chemistry (inorganic and organic ions) including mercury (Hg) speciation
      was studied in samples collected during a two-month field study in a high Arctic
      site, Svalbard, Norway (79  degrees N). Shifts in microbial community structure
      were determined by using a 16S rRNA gene phylogenetic microarray. We linked
      snowpack and meltwater chemistry to changes in microbial community structure by
      using co-inertia analyses (CIA) and explored changes in community function due to
      Hg contamination by q-PCR quantification of Hg-resistance genes in metagenomic
      samples. Based on the CIA, chemical and microbial data were linked (p = 0.006)
      with bioavailable Hg (BioHg) and methylmercury (MeHg) contributing significantly
      to the ordination of samples. Mercury was shown to influence community function
      with increases in merA gene copy numbers at low BioHg levels. Our results show
      that snowpacks can be considered as dynamic habitats with microbial and chemical
      components responding rapidly to environmental changes.

PMID- 24282516
TI  - Molecular phylogeography and evolutionary history of Poropuntius huangchuchieni
      (Cyprinidae) in Southwest China.
AB  - BACKGROUND: The evolution of the Yunnan Plateau's drainages network during the
      Pleistocene was dominated by the intense uplifts of the Qinghai-Tibetan Plateau.
      In the present study, we investigated the association between the evolutionary
      histories of three main drainage systems and the geographic patterns of genetic
      differentiation of Poropuntius huangchuchieni. METHODOLOGY/PRINCIPAL FINDINGS: We
      sequenced the complete sequences of mitochondrial control region for 304
      specimens and the sequences of Cytochrome b gene for 15 specimens of the species
      P. huangchuchieni and 5 specimens of Poropuntius opisthoptera. Phylogenetic
      analysis identified five major lineages, of which lineages MK-A and MK-B
      constrained to the Mekong River System, lineages RL and LX to the Red River
      System, and lineage SW to the Salween River System. The genetic distance and
      network analysis detected significant divergences among these lineages. Mismatch
      distribution analysis implied that the population of P. huangchuchieni underwent
      demographic stability and the lineage MK-B, sublineages MK-A1 and LX-1 underwent
      a recent population expansion. The divergence of the 5 major lineages was dated
      back to 0.73-1.57 MYA. CONCLUSIONS/SIGNIFICANCE: Our results suggest that P.
      opisthoptera was a paraphyletic group of P. huangchuchieni. The phylogenetic
      pattern of P. huangchuchieni was mostly associated with the drainage's structures
      and the geomorphological history of the Southwest Yunnan Plateau. Also the
      differentiation of the major lineages among the three drainages systems coincides
      with the Kunlun-Yellow River Movement (1.10-0.60 MYA). The genetic
      differentiation within river basins and recent demographical expansions that
      occurred in some lineages and sublineages are consistent with the palaeoclimatic
      oscillations during the Pleistocene. Additionally, our results also suggest that
      the populations of P. huangchuchieni had keep long term large effective
      population sizes and demographic stability in the recent evolutionary history,
      which may be responsible for the high genetic diversity and incomplete lineages
      sorting of Poropuntius huangchuchieni.

PMID- 24282517
TI  - Effects of highly conserved major histocompatibility complex (MHC) extended
      haplotypes on iron and low CD8+ T lymphocyte phenotypes in HFE C282Y homozygous
      hemochromatosis patients from three geographically distant areas.
AB  - Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron
      overload occurring commonly in subjects homozygous for the C282Y mutation in HFE
      gene localized on chromosome 6p21.3 in linkage disequilibrium with the human
      leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic
      expression is variable suggesting the presence of modifying factors. One such
      genetic factor, a SNP microhaplotype named A-A-T, was recently found to be
      associated with a more severe phenotype and also with low CD8(+)T-lymphocyte
      numbers. The present study aimed to test whether the predictive value of the A-A
      T microhaplotype remained in other population settings. In this study of 304 HH
      patients from 3 geographically distant populations (Porto, Portugal 65; Alabama,
      USA 57; Nord-Trondelag, Norway 182), the extended haplotypes involving A-A-T were
      studied in 608 chromosomes and the CD8(+) T-lymphocyte numbers were determined in
      all subjects. Patients from Porto had a more severe phenotype than those from
      other settings. Patients with A-A-T seemed on average to have greater iron stores
      (p = 0.021), but significant differences were not confirmed in the 3 separate
      populations. Low CD8(+) T-lymphocytes were associated with HLA-A*03-A-A-T in
      Porto and Alabama patients but not in the greater series from Nord-Trondelag.
      Although A-A-T may signal a more severe iron phenotype, this study was unable to
      prove such an association in all population settings, precluding its use as a
      universal predictive marker of iron overload in HH. Interestingly, the
      association between A-A-T and CD8(+) T-lymphocytes, which was confirmed in Porto
      and Alabama patients, was not observed in Nord-Trondelag patients, showing that
      common HLA haplotypes like A*01-B*08 or A*03-B*07 segregating with HFE/C282Y in
      the three populations may carry different messages. These findings further
      strengthen the relevance of HH as a good disease model to search for novel
      candidate loci associated with the genetic transmission of CD8(+) T-lymphocyte
      numbers.

PMID- 24282518
TI  - Exploring patient values in medical decision making: a qualitative study.
AB  - BACKGROUND: Patient decisions are influenced by their personal values. However,
      there is a lack of clarity and attention on the concept of patient values in the
      clinical context despite clear emphasis on patient values in evidence-based
      medicine and shared decision making. The aim of the study was to explore the
      concept of patient values in the context of making decisions about insulin
      initiation among people with type 2 diabetes. METHODS AND FINDINGS: We conducted
      individual in-depth interviews with people with type 2 diabetes who were making
      decisions about insulin treatment. Participants were selected purposively to
      achieve maximum variation. A semi-structured topic guide was used to guide the
      interviews which were audio-recorded and analysed using a thematic approach. We
      interviewed 21 participants between January 2011 and March 2012. The age range of
      participants was 28-67 years old. Our sample comprised 9 women and 12 men. Three
      main themes, 'treatment-specific values', 'life goals and philosophies', and
      'personal and social background', emerged from the analysis. The patients
      reported a variety of insulin-specific values, which were negative and/or
      positive beliefs about insulin. They framed insulin according to their priorities
      and philosophies in life. Patients' decisions were influenced by sociocultural
      (e.g. religious background) and personal backgrounds (e.g. family situations).
      CONCLUSIONS: This study highlighted the need for expanding the current concept of
      patient values in medical decision making. Clinicians should address more than
      just values related to treatment options. Patient values should include patients'
      priorities, life philosophy and their background. Current decision support tools,
      such as patient decision aids, should consider these new dimensions when
      clarifying patient values.

PMID- 24282519
TI  - Structural and physiological analyses of the alkanesulphonate-binding protein
      (SsuA) of the citrus pathogen Xanthomonas citri.
AB  - BACKGROUND: The uptake of sulphur-containing compounds plays a pivotal role in
      the physiology of bacteria that live in aerobic soils where organosulfur
      compounds such as sulphonates and sulphate esters represent more than 95% of the
      available sulphur. Until now, no information has been available on the uptake of
      sulphonates by bacterial plant pathogens, particularly those of the Xanthomonas
      genus, which encompasses several pathogenic species. In the present study, we
      characterised the alkanesulphonate uptake system (Ssu) of Xanthomonas axonopodis
      pv. citri 306 strain (X. citri), the etiological agent of citrus canker.
      METHODOLOGY/PRINCIPAL FINDINGS: A single operon-like gene cluster (ssuEDACB) that
      encodes both the sulphur uptake system and enzymes involved in desulphurisation
      was detected in the genomes of X. citri and of the closely related species. We
      characterised X. citri SsuA protein, a periplasmic alkanesulphonate-binding
      protein that, together with SsuC and SsuB, defines the alkanesulphonate uptake
      system. The crystal structure of SsuA bound to MOPS, MES and HEPES, which is
      herein described for the first time, provides evidence for the importance of a
      conserved dipole in sulphate group coordination, identifies specific amino acids
      interacting with the sulphate group and shows the presence of a rather large
      binding pocket that explains the rather wide range of molecules recognised by the
      protein. Isolation of an isogenic ssuA-knockout derivative of the X. citri 306
      strain showed that disruption of alkanesulphonate uptake affects both xanthan gum
      production and generation of canker lesions in sweet orange leaves.
      CONCLUSIONS/SIGNIFICANCE: The present study unravels unique structural and
      functional features of the X. citri SsuA protein and provides the first
      experimental evidence that an ABC uptake system affects the virulence of this
      phytopathogen.

PMID- 24282520
TI  - Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption
      and colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide.
      Epidemiological risk factors for CRC included alcohol intake, which is mainly
      metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to
      acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol
      metabolism pathways is of particular interest. The aim of this study is to
      analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and
      also the main effect of alcohol consumption on CRC risk in the study population.
      METHODOLOGY/PRINCIPAL FINDINGS: SNPs from ADH1B and ALDH2 genes, included in
      alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched
      controls from the Molecular Epidemiology of Colorectal Cancer study. Information
      on clinicopathological characteristics, lifestyle and dietary habits were also
      obtained. Logistic regression and association analysis were conducted. A positive
      association between alcohol consumption and CRC risk was observed in male
      participants from the Molecular Epidemiology of Colorectal Cancer study (MECC)
      study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene
      was found to be associated with CRC risk: under the recessive model, the OR was
      1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis
      based on structural equation modeling showed a direct effect of ADH1B gene
      polymorphisms on colorectal carcinogenesis and also an indirect effect mediated
      through alcohol consumption. CONCLUSIONS/SIGNIFICANCE: Genetic polymorphisms in
      the alcohol metabolism pathways have a potential role in colorectal
      carcinogenesis, probably due to the differences in the ethanol metabolism and
      acetaldehyde oxidation of these enzyme variants.

PMID- 24282521
TI  - Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.
AB  - In vertebrates and arthropods, blood clotting involves the establishment of a
      plug of aggregated thrombocytes (the cellular clot) and an extracellular
      fibrillar clot formed by the polymerization of the structural protein of the
      clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin
      in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to
      staunch bleeding. Additionally, the extracellular clot functions as an agent of
      the innate immune system by providing a passive anti-microbial barrier and
      microbial entrapment device, which functions directly at the site of wounds to
      the integument. Here we show that, in addition to these passive functions in
      immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus,
      and both the platelet thrombus and the fibrin clot of mammals (human, mouse)
      operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS
      is the principal agent of gram-negative septicemia, which is responsible for more
      than 100,000 human deaths annually in the United States and is similarly toxic to
      arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows
      that clots capture significant quantities of LPS and fluorescent-labeled LPS can
      be seen by microscopy to decorate the clot fibrils. Thrombi generated in the
      living mouse accumulate LPS in vivo. It is suggested that capture of LPS released
      from gram-negative bacteria entrapped by the blood clot operates to protect
      against the disease that might be caused by its systemic dispersal. 

PMID- 24282522
TI  - Gender differences in the association between socioeconomic status and
      subclinical atherosclerosis.
AB  - OBJECTIVES: This study explored the pattern of associations between socioeconomic
      status (SES) and atherosclerosis progression (as indicated by carotid intima
      media thickness, CIMT) across gender. DESIGN: Cross-sectional analysis of a
      sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001
      in the 3C study (France). We fitted linear regression models including
      neighborhood SES, individual SES and cardiovascular risk factors. RESULTS: CIMT
      was on average 24 um higher in men (95% CI: 17 to 31). Neighborhood SES was
      inversely associated with CIMT in women only (highest versus lowest tertiles: 
      12.2 um, 95%CI -22 to -2.4). This association persisted when individual SES and
      risk factors were accounted for. High individual education was associated with
      lower CIMT in men (-21.4 um 95%CI -37.5 to -5.3) whereas high professional status
      was linked to lower CIMT among women (-15.7 um 95%CI: -29.2 to -2.2). Adjustment
      for cardiovascular risk factors resulted in a slightly more pronounced reduction
      of the individual SES-CIMT association observed in men than in women. CONCLUSION:
      In this sample, neighborhood and individual SES displayed different patterns of
      associations with subclinical atherosclerosis across gender. This suggests that
      the causal pathways leading to SES variations in atherosclerosis may differ among
      men and women.

PMID- 24282523
TI  - Differential effects of antibiotic therapy on the structure and function of human
      gut microbiota.
AB  - The human intestinal microbiota performs many essential functions for the host.
      Antimicrobial agents, such as antibiotics (AB), are also known to disturb
      microbial community equilibrium, thereby having an impact on human physiology.
      While an increasing number of studies investigate the effects of AB usage on
      changes in human gut microbiota biodiversity, its functional effects are still
      poorly understood. We performed a follow-up study to explore the effect of ABs
      with different modes of action on human gut microbiota composition and function.
      Four individuals were treated with different antibiotics and samples were taken
      before, during and after the AB course for all of them. Changes in the total and
      in the active (growing) microbiota as well as the functional changes were
      addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches.
      We have found that the class of antibiotic, particularly its antimicrobial effect
      and mode of action, played an important role in modulating the gut microbiota
      composition and function. Furthermore, analysis of the resistome suggested that
      oscillatory dynamics are not only due to antibiotic-target resistance, but also
      to fluctuations in the surviving bacterial community. Our results indicated that
      the effect of AB on the human gut microbiota relates to the interaction of
      several factors, principally the properties of the antimicrobial agent, and the
      structure, functions and resistance genes of the microbial community. 

PMID- 24282524
TI  - Short copy number variations potentially associated with tonic immobility
      responses in newly hatched chicks.
AB  - INTRODUCTION: Tonic immobility (TI) is fear-induced freezing that animals may
      undergo when confronted by a threat. It is principally observed in prey species
      as defence mechanisms. In our preliminary research, we detected large inter
      individual variations in the frequency and duration of freezing behavior among
      newly hatched domestic chicks (Gallus gallus). In this study we aim to identify
      the copy number variations (CNVs) in the genome of chicks as genetic candidates
      that underlie the behavioral plasticity to fearful stimuli. METHODS: A total of
      110 domestic chicks were used for an association study between TI responses and
      copy number polymorphisms. Array comparative genomic hybridization (aCGH) was
      conducted between chicks with high and low TI scores using an Agilent 4 * 180
      custom microarray. We specifically focused on 3 genomic regions (>60 Mb) of
      chromosome 1 where previous quantitative trait loci (QTL) analysis showed
      significant F-values for fearful responses. RESULTS: ACGH successfully detected
      short CNVs within the regions overlapping 3 QTL peaks. Eleven of these identified
      loci were validated by real-time quantitative polymerase chain reaction (qPCR) as
      copy number polymorphisms. Although there wkas no significant p value in the
      correlation analysis between TI scores and the relative copy number within each
      breed, several CNV loci showed significant differences in the relative copy
      number between 2 breeds of chicken (White Leghorn and Nagoya) which had different
      quantitative characteristics of fear-induced responses. CONCLUSION: Our data
      shows the potential CNVs that may be responsible for innate fear response in
      domestic chicks.

PMID- 24282525
TI  - RABL6A, a novel RAB-like protein, controls centrosome amplification and
      chromosome instability in primary fibroblasts.
AB  - RABL6A (RAB-like 6 isoform A) is a novel protein that was originally identified
      based on its association with the Alternative Reading Frame (ARF) tumor
      suppressor. ARF acts through multiple p53-dependent and p53-independent pathways
      to prevent cancer. How RABL6A functions, to what extent it depends on ARF and p53
      activity, and its importance in normal cell biology are entirely unknown. We
      examined the biological consequences of RABL6A silencing in primary mouse embryo
      fibroblasts (MEFs) that express or lack ARF, p53 or both proteins. We found that
      RABL6A depletion caused centrosome amplification, aneuploidy and multinucleation
      in MEFs regardless of ARF and p53 status. The centrosome amplification in RABL6A
      depleted p53-/- MEFs resulted from centrosome reduplication via Cdk2-mediated
      hyperphosphorylation of nucleophosmin (NPM) at threonine-199. Thus, RABL6A
      prevents centrosome amplification through an ARF/p53-independent mechanism that
      restricts NPM-T199 phosphorylation. These findings demonstrate an essential role
      for RABL6A in centrosome regulation and maintenance of chromosome stability in
      non-transformed cells, key processes that ensure genomic integrity and prevent
      tumorigenesis. 

PMID- 24282526
TI  - Role of prostate apoptosis response 4 in translocation of GRP78 from the
      endoplasmic reticulum to the cell surface of trophoblastic cells.
AB  - Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) molecular
      chaperone that belongs to the heat shock protein 70 family. GRP78 is also present
      on the cell surface membrane of trophoblastic cells, where it is associated with
      invasive or fusion properties of these cells. Impaired mechanism of GRP78
      relocation from ER to the cell surface was observed in preeclamptic
      cytotrophoblastic cells (CTB) and could take part in the pathogenesis of
      preeclampsia. In this study, we have investigated whether prostate apoptosis
      response 4 (Par-4), a protein identified as a partner of GRP78 relocation to the
      cell surface in prostate cancer cells, is present in trophoblastic cells and is
      involved in the translocation of GRP78 to the cell surface of CTB. Par-4 is
      indeed present in trophoblastic cells and its expression correlates with
      expression of membrane GRP78. Moreover, overexpression of Par-4 led to an
      increase of cell surface expression of GRP78 and decreased Par-4 gene expression
      reduced cell surface localization of GRP78 confirming a role of Par-4 in
      relocation of GRP78 from ER to the cell surface. Accordingly, invasive property
      was modified in these cells. In conclusion, we show that Par-4 is expressed in
      trophoblastic cells and is involved in transport of GRP78 to the cell surface and
      thus regulates invasive property of extravillous CTB. 

PMID- 24282527
TI  - The impact of allergic rhinitis and asthma on human nasal and bronchial
      epithelial gene expression.
AB  - BACKGROUND: The link between upper and lower airways in patients with both asthma
      and allergic rhinitis is still poorly understood. As the biological complexity of
      these disorders can be captured by gene expression profiling we hypothesized that
      the clinical expression of rhinitis and/or asthma is related to differential gene
      expression between upper and lower airways epithelium. OBJECTIVE: Defining gene
      expression profiles of primary nasal and bronchial epithelial cells from the same
      individuals and examining the impact of allergic rhinitis with and without
      concomitant allergic asthma on expression profiles. METHODS: This cross-sectional
      study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic
      rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6
      subjects per group was approximately 5%. RNA was extracted from isolated and
      cultured epithelial cells from bronchial brushings and nasal biopsies, and
      analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed
      using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was
      used. RESULTS: The study was successfully completed by 17 subjects (6 allergic
      asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using
      correction for multiple testing, 1988 genes were differentially expressed between
      healthy lower and upper airway epithelium, whereas in allergic rhinitis with or
      without asthma this was only 40 and 301 genes, respectively. Genes influenced by
      allergic rhinitis with or without asthma were linked to lung development,
      remodeling, regulation of peptidases and normal epithelial barrier functions.
      CONCLUSIONS: Differences in epithelial gene expression between the upper and
      lower airway epithelium, as observed in healthy subjects, largely disappear in
      patients with allergic rhinitis with or without asthma, whilst new differences
      emerge. The present data identify several pathways and genes that might be
      potential targets for future drug development.

PMID- 24282528
TI  - TAL effectors specificity stems from negative discrimination.
AB  - Transcription Activator-Like (TAL) effectors are DNA-binding proteins secreted by
      phytopathogenic bacteria that interfere with native cellular functions by binding
      to plant DNA promoters. The key element of their architecture is a domain of
      tandem-repeats with almost identical sequences. Most of the polymorphism is
      located at two consecutive amino acids termed Repeat Variable Diresidue (RVD).
      The discovery of a direct link between the RVD composition and the targeted
      nucleotide allowed the design of TAL-derived DNA-binding tools with programmable
      specificities that revolutionized the field of genome engineering. Despite
      structural data, the molecular origins of this specificity as well as the
      recognition mechanism have remained unclear. Molecular simulations of the recent
      crystal structures suggest that most of the protein-DNA binding energy originates
      from non-specific interactions between the DNA backbone and non-variable
      residues, while RVDs contributions are negligible. Based on dynamical and
      energetic considerations we postulate that, while the first RVD residue promotes
      helix breaks--allowing folding of TAL as a DNA-wrapping super-helix--the second
      provides specificity through a negative discrimination of matches. Furthermore,
      we propose a simple pharmacophore-like model for the rationalization of RVD-DNA
      interactions and the interpretation of experimental findings concerning shared
      affinities and binding efficiencies. The explanatory paradigm presented herein
      provides a better comprehension of this elegant architecture and we hope will
      allow for improved designs of TAL-derived biotechnological tools.

PMID- 24282529
TI  - Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne
      muscular Dystrophy.
AB  - Duchenne muscular Dystrophy (DMD) is an inherited disease caused by mutations in
      the dystrophin gene that disrupt the open reading frame, while in frame mutations
      result in Becker muscular dystrophy (BMD). Ullrich congenital muscular dystrophy
      (UCMD) is due to mutations affecting collagen VI genes. Specific muscle miRNAs
      (dystromirs) are potential non-invasive biomarkers for monitoring the outcome of
      therapeutic interventions and disease progression. We quantified miR-1, miR
      133a,b, miR-206 and miR-31 in serum from patients with DMD, BMD, UCMD and healthy
      controls. MiR-1, miR-133a,b and miR-206 were upregulated in DMD, but unchanged in
      UCMD compared to controls. Milder DMD patients had higher levels of dystromirs
      than more severely affected patients. Patients with low forced vital capacity
      (FVC) values, indicating respiratory muscle weakness, had low levels of serum miR
      1 and miR-133b. There was no significant difference in the level of the
      dystromirs in BMD compared to controls. We also assessed the effect of dystrophin
      restoration on the expression of the five dystromirs in serum of DMD patients
      treated systemically for 12 weeks with antisense oligomer eteplirsen that induces
      skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in
      muscle biopsies of DMD patients included in a single dose intramuscular
      eteplirsen clinical trial. Our analysis detected a trend towards normalization of
      these miRNA between the pre- and post-treatment samples of the systemic trial,
      which however failed to reach statistical significance. This could possibly be
      due to the small number of patients and the short duration of these clinical
      trials. Although longer term studies are needed to clarify the relationship
      between dystrophin restoration following therapeutic intervention and the level
      of circulating miRNAs, our results indicate that miR-1 and miR-133 can be
      considered as exploratory biomarkers for monitoring the progression of muscle
      weakness and indirectly the remaining muscle mass in DMD. 

PMID- 24282530
TI  - miR-127 regulates cell proliferation and senescence by targeting BCL6.
AB  - Cellular senescence occurs as a response to extracellular and intracellular
      stresses and contributes to aging and age-related pathologies. Emerging evidence
      suggests that cellular senescence also acts as a potent tumor suppression
      mechanism that prevents the oncogenic transformation of primary human cells.
      Recent reports have indicated that miRNAsact as key modulators of cellular
      senescence by targeting critical regulators of the senescence pathways. We
      previously reported that miR-127 is up-regulated in senescent fibroblasts. In
      this report, we identified miR-127 as a novel regulator of cellular senescence
      that directly targets BCL6. We further showed that miR-127 is down-regulated in
      breast cancer tissues and that this down-regulation is associated with up
      regulation of BCL6. Over-expression of miR-127 or depletion of BCL6 inhibits
      breast cancer cell proliferation. Our data suggest that miR-127 may function as a
      tumor suppressor that modulates the oncogene BCL6.

PMID- 24282531
TI  - Circulating serum trefoil factor 3 (TFF3) is dramatically increased in chronic
      kidney disease.
AB  - OBJECTIVES: Trefoil factor 3 (TFF3) is a small peptide that plays an important
      role in mucosal protection, cell proliferation, and cell migration. The aberrant
      expression of TFF3 is correlated with gastrointestinal inflammation, solid
      tumors, and other clinical diseases. The objective of this study was to identify
      the distribution characteristics of serum TFF3 in common clinical diseases.
      MATERIALS AND METHODS: A large prospective randomized study of 1,072 Chinese
      patients was performed using an enzyme-linked immunosorbent assay (ELISA) to
      examine the serum TFF3 concentrations in patients with different diseases. A
      matched case-control study was conducted on patients with chronic kidney disease
      (CKD) stages 1-5. Immunohistochemistry (IHC) was performed using renal tissues to
      determine the relationship between the severity of CKD and the serum and urine
      concentrations of TFF3 peptides. RESULTS: The mean serum concentrations of TFF3
      in patients with CKD, metastatic and secondary carcinoma (MC) and acute
      gastroenteritis (AG) (200.9 ng/ml, 95.7 ng/ml and 71.7 ng/ml, respectively) were
      significantly higher than those in patients with other common clinical diseases.
      A positive correlation tendency was observed between the serum TFF3
      concentrations and the severity of CKD. The mean serum TFF3 values for CKD stages
      1-5 were 23.6 ng/ml, 29.9 ng/ml, 54.9 ng/ml, 85.0 ng/ml and 176.6 ng/ml,
      respectively. The same trend was observed in the urine TFF3 concentrations and
      the CKD stages. The creatinine(Cr)-corrected concentrations of TFF3 in urine were
      367.1 ng/mg.Cr, 910.6 ng/mg.Cr, 1,149.0 ng/mg.Cr, 1,610.0 ng/mg.Cr and 3,475.0
      ng/mg.Cr for CKD stages 1-5, respectively. IHC revealed that TFF3 expression was
      concentrated in tubular epithelial cells. CONCLUSIONS: The influence of kidney
      injuries must be fully considered when performing clinical TFF3 research. Further
      studies on TFF3 in CKD will contribute to our understanding of its pathological
      roles and mechanisms in other diseases.

PMID- 24282532
TI  - An integrated model of environmental effects on growth, carbohydrate balance, and
      mortality of Pinus ponderosa forests in the southern Rocky Mountains.
AB  - Climate-induced tree mortality is an increasing concern for forest managers
      around the world. We used a coupled hydrologic and ecosystem carbon cycling model
      to assess temperature and precipitation impacts on productivity and survival of
      ponderosa pine (Pinus ponderosa). Model predictions were evaluated using
      observations of productivity and survival for three ponderosa pine stands located
      across an 800 m elevation gradient in the southern Rocky Mountains, USA, during a
      10-year period that ended in a severe drought and extensive tree mortality at the
      lowest elevation site. We demonstrate the utility of a relatively simple
      representation of declines in non-structural carbohydrate (NSC) as an approach
      for estimating patterns of ponderosa pine vulnerability to drought and the
      likelihood of survival along an elevation gradient. We assess the sensitivity of
      simulated net primary production, NSC storage dynamics, and mortality to site
      climate and soil characteristics as well as uncertainty in the allocation of
      carbon to the NSC pool. For a fairly wide set of assumptions, the model estimates
      captured elevational gradients and temporal patterns in growth and biomass. Model
      results that best predict mortality risk also yield productivity, leaf area, and
      biomass estimates that are qualitatively consistent with observations across the
      sites. Using this constrained set of parameters, we found that productivity and
      likelihood of survival were equally dependent on elevation-driven variation in
      temperature and precipitation. Our results demonstrate the potential for a
      coupled hydrology-ecosystem carbon cycling model that includes a simple model of
      NSC dynamics to predict drought-related mortality. Given that increases in
      temperature and in the frequency and severity of drought are predicted for a
      broad range of ponderosa pine and other western North America conifer forest
      habitats, the model potentially has broad utility for assessing ecosystem
      vulnerabilities. 

PMID- 24282533
TI  - Fetal calcium regulates branching morphogenesis in the developing human and mouse
      lung: involvement of voltage-gated calcium channels.
AB  - Airway branching morphogenesis in utero is essential for optimal postnatal lung
      function. In the fetus, branching morphogenesis occurs during the pseudoglandular
      stage (weeks 9-17 of human gestation, embryonic days (E)11.5-16.5 in mouse) in a
      hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult).
      Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on
      branching morphogenesis via the calcium-sensing receptor. In addition, earlier
      studies have shown that nifedipine, a selective blocker of L-type voltage-gated
      Ca(2+) channels (VGCC), inhibits fetal lung growth, suggesting a role for VGCC in
      lung development. The aim of this work was to investigate the expression of VGCC
      in the pseudoglandular human and mouse lung, and their role in branching
      morphogenesis. Expression of L-type (CaV1.2 and CaV1.3), P/Q type (CaV2.1), N
      type (CaV2.2), R-type (CaV2.3), and T-type (CaV3.2 and CaV3.3) VGCC was
      investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse
      embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed
      in both the smooth muscle and epithelium of the developing human and mouse lung.
      Additionally, Cav2.3 was expressed in the lung epithelium of both species.
      Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the
      amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor,
      SNX-482. Direct measurements of changes in epithelial cell membrane potential,
      using the voltage-sensitive fluorescent dye DiSBAC2(3), demonstrated that cyclic
      depolarisations occur within the developing epithelium and coincide with rhythmic
      occlusions of the lumen, driven by the naturally occurring airway peristalsis. We
      conclude that VGCC are expressed and functional in the fetal human and mouse
      lung, where they play a role in branching morphogenesis. Furthermore, rhythmic
      epithelial depolarisations evoked by airway peristalsis would allow for branching
      to match growth and distension within the developing lung.

PMID- 24282534
TI  - DNA-PK target identification reveals novel links between DNA repair signaling and
      cytoskeletal regulation.
AB  - The DNA-dependent protein kinase (DNA-PK) may function as a key signaling kinase
      in various cellular pathways other than DNA repair. Using a two-dimensional gel
      electrophoresis approach and stable DNA double-strand break-mimicking molecules
      (Dbait32Hc) to activate DNA-PK in the nucleus and cytoplasm, we identified 26
      proteins that were highly phosphorylated following DNA-PK activation. Most of
      these proteins are involved in protein stability and degradation, cell signaling
      and the cytoskeleton. We investigated the relationship between DNA-PK and the
      cytoskeleton and found that the intermediate filament (IF) vimentin was a target
      of DNA-PK in vitro and in cells. Vimentin was phosphorylated at Ser459, by DNA
      PK, in cells transfected with Dbait32Hc. We produced specific antibodies and
      showed that Ser459-P-vimentin was mostly located at cell protrusions. In
      migratory cells, the vimentin phosphorylation induced by Dbait32Hc was associated
      with a lower cellular adhesion and migration capacity. Thus, this approach led to
      the identification of downstream cytoplasmic targets of DNA-PK and revealed a
      connection between DNA damage signaling and the cytoskeleton. 

PMID- 24282535
TI  - Features of effective medical knowledge resources to support point of care
      learning: a focus group study.
AB  - OBJECTIVE: Health care professionals access various information sources to
      quickly answer questions that arise in clinical practice. The features that
      favorably influence the selection and use of knowledge resources remain unclear.
      We sought to better understand how clinicians select among the various knowledge
      resources available to them, and from this to derive a model for an effective
      knowledge resource. METHODS: We conducted 11 focus groups at an academic medical
      center and outlying community sites. We included a purposive sample of 50 primary
      care and subspecialist internal medicine and family medicine physicians. We
      transcribed focus group discussions and analyzed these using a constant
      comparative approach to inductively identify features that influence the
      selection of knowledge resources. RESULTS: We identified nine features that
      influence users' selection of knowledge resources, namely efficiency (with sub
      features of comprehensiveness, searchability, and brevity), integration with
      clinical workflow, credibility, user familiarity, capacity to identify a human
      expert, reflection of local care processes, optimization for the clinical
      question (e.g., diagnosis, treatment options, drug side effect), currency, and
      ability to support patient education. No single existing resource exemplifies all
      of these features. CONCLUSION: The influential features identified in this study
      will inform the development of knowledge resources, and could serve as a
      framework for future research in this field.

PMID- 24282536
TI  - DNA-COMPACT: DNA COMpression based on a pattern-aware contextual modeling
      technique.
AB  - Genome data are becoming increasingly important for modern medicine. As the rate
      of increase in DNA sequencing outstrips the rate of increase in disk storage
      capacity, the storage and data transferring of large genome data are becoming
      important concerns for biomedical researchers. We propose a two-pass lossless
      genome compression algorithm, which highlights the synthesis of complementary
      contextual models, to improve the compression performance. The proposed framework
      could handle genome compression with and without reference sequences, and
      demonstrated performance advantages over best existing algorithms. The method for
      reference-free compression led to bit rates of 1.720 and 1.838 bits per base for
      bacteria and yeast, which were approximately 3.7% and 2.6% better than the state
      of-the-art algorithms. Regarding performance with reference, we tested on the
      first Korean personal genome sequence data set, and our proposed method
      demonstrated a 189-fold compression rate, reducing the raw file size from 2986.8
      MB to 15.8 MB at a comparable decompression cost with existing algorithms.
      DNAcompact is freely available at https://sourceforge.net/projects/dnacompact/for
      research purpose. 

PMID- 24282537
TI  - Human infant faces provoke implicit positive affective responses in parents and
      non-parents alike.
AB  - Human infants' complete dependence on adult caregiving suggests that mechanisms
      associated with adult responsiveness to infant cues might be deeply embedded in
      the brain. Behavioural and neuroimaging research has produced converging evidence
      for adults' positive disposition to infant cues, but these studies have not
      investigated directly the valence of adults' reactions, how they are moderated by
      biological and social factors, and if they relate to child caregiving. This study
      examines implicit affective responses of 90 adults toward faces of human and non
      human (cats and dogs) infants and adults. Implicit reactions were assessed with
      Single Category Implicit Association Tests, and reports of childrearing
      behaviours were assessed by the Parental Style Questionnaire. The results showed
      that human infant faces represent highly biologically relevant stimuli that
      capture attention and are implicitly associated with positive emotions. This
      reaction holds independent of gender and parenthood status and is associated with
      ideal parenting behaviors. 

PMID- 24282538
TI  - Molecular insights of genetic variation in Erianthus arundinaceus populations
      native to China.
AB  - BACKGROUND: E. arundinaceus (Retz.) Jeswiet is a warm-season, tall-growing
      perennial species native to much southern portion in China. The grass has been
      extensively used in sugarcane breeding and is recently targeted as a bioenergy
      feedstock crop. However, information on the genetic structure of the Chinese wild
      germplasm is limited. Knowledge of genetic variation within and among populations
      is essential for breeding new cultivars in the species. The major objective of
      this study was to quantify the magnitude of genetic variation among and within
      natural populations in China. METHODOLOGY/PRINCIPAL FINDINGS: In this experiment,
      we analyzed genetic variation of 164 individuals of 18 populations collected from
      natural habitats in six Chinese provinces using 20 sequence-related amplified
      polymorphism (SRAP) primer pairs generating 277 polymorphic bands. Among and
      within the populations, the percentage of polymorphic bands (PPB) was 80.00% and
      27.07%, genetic diversity (HE ) was 0.245 and 0.099, effective number of alleles
      (NE ) was 1.350 and 1.170, and Shannon's information index (I) was 0.340 and
      0.147, respectively. The populations were clustered into six groups exhibiting a
      high level of genetic differentiation, which was highly associated with
      geographic origins of respective germplasm populations, but was not significantly
      associated with geographic distances between the populations.
      CONCLUSIONS/SIGNIFICANCE: This is the first report indicating that large genetic
      variation exists in the Chinese E. arundinaceus germplasm based on the SRAP
      molecular marker analysis of native populations. The genetic structure of
      populations in the species has been substantially affected by geographic
      landforms and environments. The diverse collection will be highly valuable in
      genetic improvement in the species per se and likely in sugarcane.

PMID- 24282539
TI  - Assessing the spatiotemporal variation in distribution, extent and NPP of
      terrestrial ecosystems in response to climate change from 1911 to 2000.
AB  - To assess the variation in distribution, extent, and NPP of global natural
      vegetation in response to climate change in the period 1911-2000 and to provide a
      feasible method for climate change research in regions where historical data is
      difficult to obtain. In this research, variations in spatiotemporal distributions
      of global potential natural vegetation (PNV) from 1911 to 2000 were analyzed with
      the comprehensive sequential classification system (CSCS) and net primary
      production (NPP) of different ecosystems was evaluated with the synthetic model
      to determine the effect of climate change on the terrestrial ecosystems. The
      results showed that consistently rising global temperature and altered
      precipitation patterns had exerted strong influence on spatiotemporal
      distribution and productivities of terrestrial ecosystems, especially in the
      mid/high latitudes. Ecosystems in temperate zones expanded and desert area
      decreased as a consequence of climate variations. The vegetation that decreased
      the most was cold desert (18.79%), while the maximum increase (10.31%) was
      recorded in savanna. Additionally, the area of tundra and alpine steppe reduced
      significantly (5.43%) and were forced northward due to significant ascending
      temperature in the northern hemisphere. The global terrestrial ecosystems
      productivities increased by 2.09%, most of which was attributed to savanna
      (6.04%), tropical forest (0.99%), and temperate forest (5.49%). Most NPP losses
      were found in cold desert (27.33%). NPP increases displayed a latitudinal
      distribution. The NPP of tropical zones amounted to more than a half of total
      NPP, with an estimated increase of 1.32%. The increase in northern temperate zone
      was the second highest with 3.55%. Global NPP showed a significant positive
      correlation with mean annual precipitation in comparison with mean annual
      temperature and biological temperature. In general, effects of climate change on
      terrestrial ecosystems were deep and profound in 1911-2000, especially in the
      latter half of the period. 

PMID- 24282541
TI  - Investigating annual diving behaviour by hooded seals (Cystophora cristata)
      within the Northwest Atlantic Ocean.
AB  - With the exception of relatively brief periods when they reproduce and moult,
      hooded seals, Cystophora cristata, spend most of the year in the open ocean where
      they undergo feeding migrations to either recover or prepare for the next fasting
      period. Valuable insights into habitat use and diving behaviour during these
      periods have been obtained by attaching Satellite Relay Data Loggers (SRDLs) to
      51 Northwest (NW) Atlantic hooded seals (33 females and 18 males) during ice
      bound fasting periods (2004-2008). Using General Additive Models (GAMs) we
      describe habitat use in terms of First Passage Time (FPT) and analyse how
      bathymetry, seasonality and FPT influence the hooded seals' diving behaviour
      described by maximum dive depth, dive duration and surface duration. Adult NW
      Atlantic hooded seals exhibit a change in diving activity in areas where they
      spend >20 h by increasing maximum dive depth, dive duration and surface duration,
      indicating a restricted search behaviour. We found that male and female hooded
      seals are spatially segregated and that diving behaviour varies between sexes in
      relation to habitat properties and seasonality. Migration periods are described
      by increased dive duration for both sexes with a peak in May, October and
      January. Males demonstrated an increase in dive depth and dive duration towards
      May (post-breeding/pre-moult) and August-October (post-moult/pre-breeding) but
      did not show any pronounced increase in surface duration. Females dived deepest
      and had the highest surface duration between December and January (post-moult/pre
      breeding). Our results suggest that the smaller females may have a greater need
      to recover from dives than that of the larger males. Horizontal segregation could
      have evolved as a result of a resource partitioning strategy to avoid sexual
      competition or that the energy requirements of males and females are different
      due to different energy expenditure during fasting periods. 

PMID- 24282542
TI  - Determining the extent and characterizing coral reef habitats of the northern
      latitudes of the Florida Reef Tract (Martin County).
AB  - Climate change has recently been implicated in poleward shifts of many tropical
      species including corals; thus attention focused on higher-latitude coral
      communities is warranted to investigate possible range expansions and ecosystem
      shifts due to global warming. As the northern extension of the Florida Reef Tract
      (FRT), the third-largest barrier reef ecosystem in the world, southeast Florida
      (25-27 degrees  N latitude) is a prime region to study such effects. Most of the
      shallow-water FRT benthic habitats have been mapped, however minimal data and
      limited knowledge exist about the coral reef communities of its northernmost
      reaches off Martin County. First benthic habitat mapping was conducted using
      newly acquired high resolution LIDAR bathymetry and aerial photography where
      possible to map the spatial extent of coral reef habitats. Quantitative data were
      collected to characterize benthic cover and stony coral demographics and a
      comprehensive accuracy assessment was performed. The data were then analyzed in a
      habitat biogeography context to determine if a new coral reef ecosystem region
      designation was warranted. Of the 374 km(2) seafloor mapped, 95.2% was Sand, 4.1%
      was Coral Reef and Colonized Pavement, and 0.7% was Other Delineations. Map
      accuracy assessment yielded an overall accuracy of 94.9% once adjusted for known
      map marginal proportions. Cluster analysis of cross-shelf habitat type and widths
      indicated that the benthic habitats were different than those further south and
      warranted designation of a new coral reef ecosystem region. Unlike the FRT
      further south, coral communities were dominated by cold-water tolerant species
      and LIDAR morphology indicated no evidence of historic reef growth during warmer
      climates. Present-day hydrographic conditions may be inhibiting poleward
      expansion of coral communities along Florida. This study provides new information
      on the benthic community composition of the northern FRT, serving as a baseline
      for future community shift and range expansion investigations. 

PMID- 24282540
TI  - Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA
      recombination.
AB  - Class switch DNA recombination (CSR) of the immunoglobulin heavy chain (IgH)
      locus crucially diversifies antibody biological effector functions. CSR involves
      the induction of activation-induced cytidine deaminase (AID) expression and AID
      targeting to switch (S) regions by 14-3-3 adaptors. 14-3-3 adaptors specifically
      bind to 5'-AGCT-3' repeats, which make up for the core of all IgH locus S
      regions. They selectively target the upstream and downstream S regions that are
      set to undergo S-S DNA recombination. We hypothesized that 14-3-3 adaptors
      function as scaffolds to stabilize CSR enzymatic elements on S regions. Here we
      demonstrate that all seven 14-3-3beta, 14-3-3epsilon, 14-3-3gamma, 14-3-3eta, 14
      3-3sigma, 14-3-3tau and 14-3-3zeta adaptors directly interacted with AID, PKA
      Calpha (catalytic subunit) and PKA-RIalpha (regulatory inhibitory subunit) and
      uracil DNA glycosylase (Ung). 14-3-3 adaptors, however, did not interact with AID
      C-terminal truncation mutant AIDDelta(180-198) or AIDF193A and AIDL196A point
      mutants (which have been shown not to bind to S region DNA and fail to mediate
      CSR). 14-3-3 adaptors colocalized with AID and replication protein A (RPA) in B
      cells undergoing CSR. 14-3-3 and AID binding to S region DNA was disrupted by
      viral protein R (Vpr), an accessory protein of human immunodeficiency virus type
      1 (HIV-1), which inhibited CSR without altering AID expression or germline IH-CH
      transcription. Accordingly, we demonstrated that 14-3-3 directly interact with
      Vpr, which in turn, also interact with AID, PKA-Calpha and Ung. Altogether, our
      findings suggest that 14-3-3 adaptors play important scaffold functions and
      nucleate the assembly of multiple CSR factors on S regions. They also show that
      such assembly can be disrupted by a viral protein, thereby allowing us to
      hypothesize that small molecule compounds that specifically block 14-3-3
      interactions with AID, PKA and/or Ung can be used to inhibit unwanted CSR. 

PMID- 24282543
TI  - Cannabinoid CB2 receptors regulate central sensitization and pain responses
      associated with osteoarthritis of the knee joint.
AB  - Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic,
      debilitating pain. Recent clinical evidence has demonstrated that central
      sensitization contributes to OA pain. An improved understanding of how OA joint
      pathology impacts upon the central processing of pain is crucial for the
      identification of novel analgesic targets/new therapeutic strategies. Inhibitory
      cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and
      modulate central neuro-immune responses in models of neurodegeneration. Systemic
      administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain
      behaviour, and the changes in circulating pro- and anti-inflammatory cytokines
      exhibited in this model. Electrophysiological studies revealed that spinal
      administration of JWH133 inhibited noxious-evoked responses of spinal neurones in
      the model of OA pain, but not in control rats, indicating a novel spinal role of
      this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA
      and protein expression in an OA pain model. The expression of CB2 receptor
      protein by both neurones and microglia in the spinal cord was significantly
      increased in the model of OA. Hallmarks of central sensitization, significant
      spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9
      in the spinal cord were evident in the model of OA pain. Systemic administration
      of JWH133 attenuated these markers of central sensitization, providing a
      neurobiological basis for analgesic effects of the CB2 receptor in this model of
      OA pain. Analysis of human spinal cord revealed a negative correlation between
      spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data
      provide new clinically relevant evidence that joint damage and spinal CB2
      receptor expression are correlated combined with converging pre-clinical evidence
      that activation of CB2 receptors inhibits central sensitization and its
      contribution to the manifestation of chronic OA pain. These findings suggest that
      targeting CB2 receptors may have therapeutic potential for treating OA pain. 

PMID- 24282544
TI  - Potential 'ecological traps' of restored landscapes: koalas Phascolarctos
      cinereus re-occupy a rehabilitated mine site.
AB  - With progressively increasing anthropogenic habitat disturbances, restoration of
      impacted landscapes is becoming a critical element of biodiversity conservation.
      Evaluation of success in restoration ecology rarely includes faunal components,
      usually only encompassing abiotic and floral components of the ecosystems. Even
      when fauna is explicitly included, it is usually only species presence/absence
      criteria that are considered. If restoration is to have a positive outcome,
      however, populations in restored habitats should exhibit comparable survival and
      reproductive rates to populations found in undisturbed surroundings. If a species
      recolonises restored areas but later experiences decreased fitness, restored
      areas could become ecological sinks or traps. We investigated this possibility in
      a case study of koalas Phascolarctos cinereus occupying rehabilitated mining
      areas on North Stradbroke Island, Australia. Our holistic approach compared
      rehabilitated and undisturbed areas on the basis of their vegetation
      characteristics, of koalas' body condition, roosting trees, diet, as well as
      predator index. Koalas using rehabilitated areas appeared to be able to access an
      adequate supply of roosting and fodder trees, were in good condition and had high
      reproductive output. We did not find any significant differences in predator
      density between rehabilitated areas and undisturbed surroundings. The results
      presented in this study showed there was no evidence that the post-mining
      rehabilitated areas constitute ecological sinks or traps. However, to reach a
      definitive conclusion as to whether areas rehabilitated post-mining provide at
      least equivalent habitat to undisturbed locations, additional research could be
      undertaken to assess foliar nutrient/water/toxin differences and predation risk
      in rehabilitated areas compared with undisturbed areas. More generally, the
      evaluation of whether restoration successfully produces a functional ecological
      community should include criteria on the fitness of faunal populations
      reoccupying such sites, so as to ensure functioning ecosystems, rather than
      ecological sinks or traps, are the outcome. 

PMID- 24282545
TI  - Comparison of EEG-features and classification methods for motor imagery in
      patients with disorders of consciousness.
AB  - Current research aims at identifying voluntary brain activation in patients who
      are behaviorally diagnosed as being unconscious, but are able to perform commands
      by modulating their brain activity patterns. This involves machine learning
      techniques and feature extraction methods such as applied in brain computer
      interfaces. In this study, we try to answer the question if
      features/classification methods which show advantages in healthy participants are
      also accurate when applied to data of patients with disorders of consciousness. A
      sample of healthy participants (N = 22), patients in a minimally conscious state
      (MCS; N = 5), and with unresponsive wakefulness syndrome (UWS; N = 9) was
      examined with a motor imagery task which involved imagery of moving both hands
      and an instruction to hold both hands firm. We extracted a set of 20 features
      from the electroencephalogram and used linear discriminant analysis, k-nearest
      neighbor classification, and support vector machines (SVM) as classification
      methods. In healthy participants, the best classification accuracies were seen
      with coherences (mean = .79; range = .53-.94) and power spectra (mean = .69;
      range = .40-.85). The coherence patterns in healthy participants did not match
      the expectation of central modulated [Formula: see text]-rhythm. Instead,
      coherence involved mainly frontal regions. In healthy participants, the best
      classification tool was SVM. Five patients had at least one feature-classifier
      outcome with p[Formula: see text]0.05 (none of which were coherence or power
      spectra), though none remained significant after false-discovery rate correction
      for multiple comparisons. The present work suggests the use of coherences in
      patients with disorders of consciousness because they show high reliability among
      healthy subjects and patient groups. However, feature extraction and
      classification is a challenging task in unresponsive patients because there is no
      ground truth to validate the results.

PMID- 24282546
TI  - Multiple independent introductions of HIV-1 CRF01_AE identified in China: what
      are the implications for prevention?
AB  - BACKGROUND: HIV-1 CRF01_AE accounts for an important fraction of HIV infections
      in Asia including China, but little is known about the phylogenetic and
      evolutionary history of this CRF (circulating recombinant form). In the current
      study, we collected a large number of 1,957 CRF01_AE gag p17 sequences with known
      sampling year (1990-2010) from 5 global regions representing 15 countries to
      better understand the phylogenetic relationships and epidemic history of CRF01_AE
      strains in China. METHODOLOGY/PRINCIPAL FINDINGS: CRF01_AE gag p17 sequences were
      retrieved from public databases to explore phylogenetic relationships and
      phylogeographic dynamics of CRF01_AE in Asia by using maximum-likelihood
      phylogenetics and Bayesian coalescent-based analyses. We found close phylogenetic
      relationships between sequences from Thailand, Vietnam and China. Moreover, at
      least 5 independent introductions and 5 independent autochthonous clades of
      CRF01_AE, which descended from Thailand or Vietnam were identified in China from
      1991 through 2003. CONCLUSION/SIGNIFICANCE: The current study not only defines
      the migration of CRF01_AE clades to/in Asia, but also demonstrates the
      criticalness of identifying the circulating strains in the population for the
      development of vaccine and microbicides.

PMID- 24282547
TI  - Environmentally enriched male mink gain more copulations than stereotypic, barren
      reared competitors.
AB  - Wild carnivores in zoos, conservation breeding centres, and farms commonly live
      in relatively small, unstimulating enclosures. Under these captive conditions, in
      a range of species including giant pandas, black-footed ferrets, and European
      mink, male reproductive abilities are often poor. Such problems have long been
      hypothesized to be caused by these animals' housing conditions. We show for the
      first time that rearing under welfare-improving (i.e., highly valued and stress
      reducing) environmental enrichments enhances male carnivores' copulatory
      performance: in mate choice competitions, enriched male American mink (Neovison
      vison) mated more often than non-enriched males. We screened for several
      potential mediators of this effect. First was physiological stress and its impact
      on reproductive physiology; second, stress-mediated changes in morphology and
      variables related to immunocompetence that could influence male attractiveness;
      and third, behavioural changes likely to affect social competence, particularly
      autistic-like excessive routine and repetition ('perseveration') as is reflected
      in the stereotypies common in captive animals. Consistent with physiological
      stress, excreted steroid metabolites revealed that non-enriched males had higher
      cortisol levels and lower androgen levels than enriched conspecifics. Their os
      penises (bacula) also tended to be less developed. Consistent with reduced
      attractiveness, non-enriched males were lighter, with comparatively small spleens
      and a trend to greater fluctuating asymmetry. Consistent with impaired social
      competence, non-enriched males performed more stereotypic behaviour (e.g.,
      pacing) in their home cages. Of all these effects, the only significant predictor
      of copulation number was stereotypy (a trend suggesting that low bodyweights may
      also be influential): highly stereotypic males gained the fewest copulations. The
      neurophysiological changes underlying stereotypy thus handicap males sexually. We
      hypothesise that such males are abnormally perseverative when interacting with
      females. Investigating similar problems in other taxa would be worthwhile, since
      many vertebrates, wild and domestic, live in conditions that cause stereotypic
      behaviour and/or impair neurological development. 

PMID- 24282548
TI  - The prevalence and determinants of undiagnosed and diagnosed type 2 diabetes in
      middle-aged irish adults.
AB  - BACKGROUND: The prevalence of type 2 diabetes within the Republic of Ireland is
      poorly defined, although a recent report suggested 135,000 cases in adults aged
      45+, with approximately one-third of these undiagnosed. This study aims to assess
      the prevalence of undiagnosed and diagnosed diabetes in middle-aged adults, and
      compare features related to either condition, in order to investigate why certain
      individuals remain undetected. METHODS: This was a cross-sectional study
      involving a sample of 2,047 men and women, aged between 50-69 years, randomly
      selected from a large primary care centre. Univariate logistic regression was
      used to explore socio-economic, metabolic and other health related variable
      associations with undiagnosed or diagnosed diabetes. A final multivariate
      analysis was used to determine odds ratios and 95% confidence intervals for
      having undiagnosed compared to diagnosed diabetes, adjusted for gender, age and
      significant covariates determined from univariate models. PRINCIPLE FINDINGS: The
      total prevalence of diabetes was 8.5% (95% CI: 7.4%-8.8%); 72 subjects (3.5%) had
      undiagnosed diabetes (95% CI: 2.8%-4.4%) and 102 subjects (5.0%) had diagnosed
      diabetes (95% CI: 4.1%-6.0%). Obesity, dyslipidaemia, and family history of
      diabetes were positively associated with both undiagnosed and diagnosed type 2
      diabetes. Compared with diagnosed subjects, study participants with undiagnosed
      diabetes were significantly more likely to have low levels of physical activity
      and were less likely to be on treatment for diabetes-related conditions or to
      have private medical insurance. CONCLUSIONS: The prevalence of diabetes within
      the Cork and Kerry Diabetes and Heart Disease Study is comparable to recent
      estimates from the Slan National Health and Lifestyle Survey, a study which was
      nationally representative of the general population. A considerable proportion of
      diabetes cases were undiagnosed (41%), emphasising the need for more effective
      detection strategies and equitable access to primary healthcare.

PMID- 24282549
TI  - Biosynthesis and uptake of copper nanoparticles by dead biomass of Hypocrea lixii
      isolated from the metal mine in the Brazilian Amazon Region.
AB  - A biological system for the biosynthesis of nanoparticles (NPs) and uptake of
      copper from wastewater, using dead biomass of Hypocrea lixii was analyzed and
      described for the first time. The equilibrium and kinetics investigation of the
      biosorption of copper onto dead, dried and live biomass of fungus were performed
      as a function of initial metal concentration, pH, temperature, agitation and
      inoculum volume. The high biosorption capacity was observed for dead biomass,
      completed within 60 min of contact, at pH 5.0, temperature of 40  degrees C and
      agitation speed of 150 rpm with a maximum copper biosorption of 19.0 mg g(-1).
      The equilibrium data were better described using the Langmuir isotherm and
      kinetic analysis indicated that copper biosorption follows a pseudo-second-order
      model. The average size, morphology and location of NPs biosynthesized by the
      fungus were determined by scanning electron microscopy (SEM), energy dispersive X
      ray spectroscopy (EDS) and transmission electron microscopy (TEM). NPs were
      mainly spherical, with an average size of 24.5 nm, and were synthesized
      extracellularly. The X-ray diffraction (XRD) analysis confirms the presence of
      metallic copper particles. Infrared spectroscopy (FTIR) study revealed that the
      amide groups interact with the particles, which was accountable for the stability
      of NPs. This method further confirmed the presence of proteins as stabilizing and
      capping agents surrounding the copper NPs. These studies demonstrate that dead
      biomass of Hypocrea lixii provides an economic and technically feasible option
      for bioremediation of wastewater and is a potential candidate for industrial
      scale production of copper NPs.

PMID- 24282551
TI  - Bleaching susceptibility and recovery of Colombian Caribbean corals in response
      to water current exposure and seasonal upwelling.
AB  - Coral bleaching events are globally occurring more frequently and with higher
      intensity, mainly caused by increases in seawater temperature. In Tayrona
      National Natural Park (TNNP) in the Colombian Caribbean, local coral communities
      are subjected to seasonal wind-triggered upwelling events coinciding with
      stronger water currents depending on location. This natural phenomenon offers the
      unique opportunity to study potential water current-induced mitigation mechanisms
      of coral bleaching in an upwelling influenced region. Therefore, coral bleaching
      susceptibility and recovery patterns were compared during a moderate and a mild
      bleaching event in December 2010 and 2011, and at the end of the subsequent
      upwelling periods at a water current-exposed and -sheltered site of an exemplary
      bay using permanent transect and labeling tools. This was accompanied by parallel
      monitoring of key environmental variables. Findings revealed that in 2010 overall
      coral bleaching before upwelling was significantly higher at the sheltered (34%)
      compared to the exposed site (8%). Whereas 97% of all previously bleached corals
      at the water current-exposed site had recovered from bleaching by April 2011,
      only 77% recovered at the sheltered site, but 12% had died there. In December
      2011, only mild bleaching (<10% at both sites) was observed, but corals recovered
      significantly at both sites in the course of upwelling. No differences in water
      temperatures between sites occurred, but water current exposure and turbidity
      were significantly higher at the exposed site, suggesting that these variables
      may be responsible for the observed site-specific mitigation of coral bleaching.
      This indicates the existence of local resilience patterns against coral bleaching
      in Caribbean reefs. 

PMID- 24282550
TI  - Proteasome, but not autophagy, disruption results in severe eye and wing
      dysmorphia: a subunit- and regulator-dependent process in Drosophila.
AB  - Proteasome-dependent and autophagy-mediated degradation of eukaryotic cellular
      proteins represent the two major proteostatic mechanisms that are critically
      implicated in a number of signaling pathways and cellular processes. Deregulation
      of functions engaged in protein elimination frequently leads to development of
      morbid states and diseases. In this context, and through the utilization of
      GAL4/UAS genetic tool, we herein examined the in vivo contribution of proteasome
      and autophagy systems in Drosophila eye and wing morphogenesis. By exploiting the
      ability of GAL4-ninaE. GMR and P{GawB}Bx(MS1096) genetic drivers to be strongly
      and preferentially expressed in the eye and wing discs, respectively, we proved
      that proteasomal integrity and ubiquitination proficiency essentially control
      fly's eye and wing development. Indeed, subunit- and regulator-specific patterns
      of severe organ dysmorphia were obtained after the RNAi-induced downregulation of
      critical proteasome components (Rpn1, Rpn2, alpha5, beta5 and beta6) or distinct
      protein-ubiquitin conjugators (UbcD6, but not UbcD1 and UbcD4). Proteasome
      deficient eyes presented with either rough phenotypes or strongly dysmorphic
      shapes, while transgenic mutant wings were severely folded and carried blistered
      structures together with loss of vein differentiation. Moreover, transgenic fly
      eyes overexpressing the UBP2-yeast deubiquitinase enzyme were characterized by an
      eyeless-like phenotype. Therefore, the proteasome/ubiquitin proteolytic
      activities are undoubtedly required for the normal course of eye and wing
      development. In contrast, the RNAi-mediated downregulation of critical Atg (1, 4,
      7, 9 and 18) autophagic proteins revealed their non-essential, or redundant,
      functional roles in Drosophila eye and wing formation under physiological growth
      conditions, since their reduced expression levels could only marginally disturb
      wing's, but not eye's, morphogenetic organization and architecture. However, Atg9
      proved indispensable for the maintenance of structural integrity of adult wings
      in aged flies. In toto, our findings clearly demonstrate the gene-specific
      fundamental contribution of proteasome, but not autophagy, in invertebrate eye
      and wing organ development. 

PMID- 24282553
TI  - Full inactivation of human influenza virus by high hydrostatic pressure preserves
      virus structure and membrane fusion while conferring protection to mice against
      infection.
AB  - Whole inactivated vaccines (WIVs) possess greater immunogenicity than split or
      subunit vaccines, and recent studies have demonstrated that WIVs with preserved
      fusogenic activity are more protective than non-fusogenic WIVs. In this work, we
      describe the inactivation of human influenza virus X-31 by high hydrostatic
      pressure (HHP) and analyze the effects on the structure by spectroscopic
      measurements, light scattering, and electron microscopy. We also investigated the
      effects of HHP on the glycoprotein activity and fusogenic activity of the viral
      particles. The electron microscopy data showed pore formation on the viral
      envelope, but the general morphology was preserved, and small variations were
      seen in the particle structure. The activity of hemagglutinin (HA) during the
      process of binding and fusion was affected in a time-dependent manner, but
      neuraminidase (NA) activity was not affected. Infectious activity ceased after 3
      hours of pressurization, and mice were protected from infection after being
      vaccinated. Our results revealed full viral inactivation with overall
      preservation of viral structure and maintenance of fusogenic activity, thereby
      conferring protection against infection. A strong response consisting of serum
      immunoglobulin IgG1, IgG2a, and serum and mucosal IgA was also detected after
      vaccination. Thus, our data strongly suggest that applying hydrostatic pressure
      may be an effective method for developing new vaccines against influenza A as
      well as other viruses. 

PMID- 24282552
TI  - X-linked MTMR8 diversity and evolutionary history of sub-Saharan populations.
AB  - The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of
      111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the
      early evolutionary history of sub-Saharan Africans and the out-of-Africa
      expansion. The analyses revealed a complex genetic structure of the Africans that
      contributed to the emergence of modern humans. We observed partitioning of two
      thirds of old lineages among southern, west/central and east African populations
      indicating ancient population stratification predating the out of Africa
      migration. Age estimates of these lineages, older than coalescence times of
      uniparentally inherited markers, raise the question whether contemporary humans
      originated from a single population or as an amalgamation of different
      populations separated by years of independent evolution, thus suggesting a
      greater antiquity of our species than generally assumed. While the oldest sub
      Saharan lineages, ~500 thousand years, are found among Khoe-San from southern
      Africa, a distinct haplotype found among Biaka is likely due to admixture from an
      even older population. An East African population that gave rise to non-Africans
      underwent a selective sweep affecting the subcentromeric region where MTMR8 is
      located. This and similar sweeps in four other regions of the X chromosome,
      documented in the literature, effectively reduced genetic diversity of non
      African chromosomes and therefore may have exacerbated the effect of the
      demographic bottleneck usually ascribed to the out of Africa migration. Our data
      is suggestive, however, that a bottleneck, occurred in Africa before range
      expansion.

PMID- 24282554
TI  - Can mass trapping reduce thrips damage and is it economically viable? Management
      of the Western flower thrips in strawberry.
AB  - The western flower thrips Frankliniella occidentalis (Pergande) (Thysanoptera:
      Thripidae) is a cosmopolitan, polyphagous insect pest that causes bronzing to
      fruit of strawberry (Fragaria x ananassa). The main aim of this study was to test
      whether mass trapping could reduce damage and to predict whether this approach
      would be economically viable. In semi-protected strawberry crops, mass trapping
      of F. occidentalis using blue sticky roller traps reduced adult thrips numbers
      per flower by 61% and fruit bronzing by 55%. The addition of the F. occidentalis
      aggregation pheromone, neryl (S)-2-methylbutanoate, to the traps doubled the trap
      catch, reduced adult thrips numbers per flower by 73% and fruit bronzing by 68%.
      The factors affecting trapping efficiency through the season are discussed.
      Damage that would result in downgrading of fruit to a cheaper price occurred when
      bronzing affected about 10% of the red fruit surface. Cost-benefit analysis using
      this threshold showed that mass trapping of thrips using blue sticky roller traps
      can be cost-effective in high-value crops. The addition of blue sticky roller
      traps to an integrated pest management programme maintained thrips numbers below
      the damage threshold and increased grower returns by a conservative estimate of
      L2.2k per hectare. Further work is required to develop the F. occidentalis
      aggregation pheromone for mass trapping and to determine the best timing for trap
      deployment. Mass trapping of thrips is likely to be cost-effective in other
      countries and other high-value crops affected by F. occidentalis damage, such as
      cucumber and cut flowers. 

PMID- 24282555
TI  - A potential benefit of albinism in Astyanax cavefish: downregulation of the oca2
      gene increases tyrosine and catecholamine levels as an alternative to melanin
      synthesis.
AB  - Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of
      cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax
      mexicanus, which has a pigmented surface dwelling form (surface fish) and several
      albino cave-dwelling forms (cavefish), albinism is caused by loss of function
      mutations in the oca2 gene, which operates during the first step of the melanin
      synthesis pathway. In addition to albinism, cavefish have evolved differences in
      behavior, including feeding and sleep, which are under the control of the
      catecholamine system. The catecholamine and melanin synthesis pathways diverge
      after beginning with the same substrate, L-tyrosine. Here we describe a novel
      relationship between the catecholamine and melanin synthesis pathways in
      Astyanax. Our results show significant increases in L-tyrosine, dopamine, and
      norepinephrine in pre-feeding larvae and adult brains of Pachon cavefish relative
      to surface fish. In addition, norepinephrine is elevated in cavefish adult
      kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal
      cells. We further show that the oca2 gene is expressed during surface fish
      development but is downregulated in cavefish embryos. A key finding is that
      knockdown of oca2 expression in surface fish embryos delays the development of
      pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We
      conclude that a potential evolutionary benefit of albinism in Astyanax cavefish
      may be to provide surplus L-tyrosine as a precursor for the elevated
      catecholamine synthesis pathway, which could be important for adaptation to the
      challenging cave environment. 

PMID- 24282556
TI  - Homeotic Gene teashirt (tsh) has a neuroprotective function in amyloid-beta 42
      mediated neurodegeneration.
AB  - BACKGROUND: Alzheimer's disease (AD) is a debilitating age related progressive
      neurodegenerative disorder characterized by the loss of cognition, and eventual
      death of the affected individual. One of the major causes of AD is the
      accumulation of Amyloid-beta 42 (Abeta42) polypeptides formed by the improper
      cleavage of amyloid precursor protein (APP) in the brain. These plaques disrupt
      normal cellular processes through oxidative stress and aberrant signaling
      resulting in the loss of synaptic activity and death of the neurons. However, the
      detailed genetic mechanism(s) responsible for this neurodegeneration still remain
      elusive. METHODOLOGY/ PRINCIPLE FINDINGS: We have generated a transgenic
      Drosophila eye model where high levels of human Abeta42 is misexpressed in the
      differentiating photoreceptor neurons of the developing eye, which phenocopy
      Alzheimer's like neuropathology in the neural retina. We have utilized this model
      for a gain of function screen using members of various signaling pathways
      involved in the development of the fly eye to identify downstream targets or
      modifiers of Abeta42 mediated neurodegeneration. We have identified the homeotic
      gene teashirt (tsh) as a suppressor of the Abeta42 mediated neurodegenerative
      phenotype. Targeted misexpression of tsh with Abeta42 in the differentiating
      retina can significantly rescue neurodegeneration by blocking cell death. We
      found that Tsh protein is absent/ downregulated in the neural retina at this
      stage. The structure function analysis revealed that the PLDLS domain of Tsh acts
      as an inhibitor of the neuroprotective function of tsh in the Drosophila eye
      model. Lastly, we found that the tsh paralog, tiptop (tio) can also rescue
      Abeta42 mediated neurodegeneration. CONCLUSIONS/SIGNIFICANCE: We have identified
      tsh and tio as new genetic modifiers of Abeta42 mediated neurodegeneration. Our
      studies demonstrate a novel neuroprotective function of tsh and its paralog tio
      in Abeta42 mediated neurodegeneration. The neuroprotective function of tsh is
      independent of its role in retinal determination.

PMID- 24282557
TI  - Timing and patterns in the taxonomic diversification of Lepidoptera (butterflies
      and moths).
AB  - The macroevolutionary history of the megadiverse insect order Lepidoptera remains
      little-known, yet coevolutionary dynamics with their angiospermous host plants
      are thought to have influenced their diversification significantly. We estimate
      the divergence times of all higher-level lineages of Lepidoptera, including most
      extant families. We find that the diversification of major lineages in
      Lepidoptera are approximately equal in age to the crown group of angiosperms and
      that there appear to have been three significant increases in diversification
      rates among Lepidoptera over evolutionary time: 1) at the origin of the crown
      group of Ditrysia about 150 million years ago (mya), 2) at the origin of the stem
      group of Apoditrysia about 120 mya and finally 3) a spectacular increase at the
      origin of the stem group of the quadrifid noctuoids about 70 mya. In addition,
      there appears to be a significant increase in diversification rate in multiple
      lineages around 90 mya, which is concordant with the radiation of angiosperms.
      Almost all extant families appear to have begun diversifying soon after the
      Cretaceous/Paleogene event 65.51 mya. 

PMID- 24282558
TI  - Tumor-specific chromosome mis-segregation controls cancer plasticity by
      maintaining tumor heterogeneity.
AB  - Aneuploidy with chromosome instability is a cancer hallmark. We studied
      chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary
      cultures derived from them. We found tumor heterogeneity with cells having Chr7
      CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade
      gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas.
      Interestingly, all Chr7-aneuploid cell types in the parental culture of
      established glioma cell lines reappeared in single-cell-derived subcultures. We
      then characterized the biology of three syngeneic glioma cultures dominated by
      different Chr7-aneuploid cell types. We found phenotypic divergence for cells
      following Chr7 mis-segregation, which benefited overall tumor growth in vitro and
      in vivo. Mathematical modeling suggested the involvement of chromosome
      instability and interactions among cell subpopulations in restoring the optimal
      equilibrium of tumor cell types. Both our experimental data and mathematical
      modeling demonstrated that the complexity of tumor heterogeneity could be
      enhanced by the existence of chromosomes with structural abnormality, in addition
      to their mis-segregations. Overall, our findings show, for the first time, the
      involvement of chromosome instability in maintaining tumor heterogeneity, which
      underlies the enhanced growth, persistence and treatment resistance of cancers. 

PMID- 24282559
TI  - Analytic review of modeling studies of ARV Based PrEP interventions reveals
      strong influence of drug-resistance assumptions on the population-level
      effectiveness.
AB  - BACKGROUND: Four clinical trials have shown that oral and topical pre-exposure
      prophylaxis (PrEP) based on tenofovir may be effective in preventing HIV
      transmission. The expected reduction in HIV transmission and the projected
      prevalence of drug resistance due to PrEP use vary significantly across modeling
      studies as a result of the broad spectrum of assumptions employed. Our goal is to
      quantify the influence of drug resistance assumptions on the predicted population
      level impact of PrEP. METHODS: All modeling studies which evaluate the impact of
      oral or topical PrEP are reviewed and key assumptions regarding mechanisms of
      generation and spread of drug-resistant HIV are identified. A dynamic model of
      the HIV epidemic is developed to assess and compare the impact of oral PrEP using
      resistance assumptions extracted from published studies. The benefits and risks
      associated with ten years of PrEP use are evaluated under identical epidemic,
      behavioral and intervention conditions in terms of cumulative fractions of new
      HIV infections prevented, resistance prevalence among those infected with HIV,
      and fractions of infections in which resistance is transmitted. RESULTS:
      Published models demonstrate enormous variability in resistance-generating
      assumptions and uncertainty in parameter values. Depending on which resistance
      parameterization is used, a resistance prevalence between 2% and 44% may be
      expected if 50% efficacious oral PrEP is used consistently by 50% of the
      population over ten years. We estimated that resistance may be responsible for up
      to a 10% reduction or up to a 30% contribution to the fraction of prevented
      infections predicted in different studies. CONCLUSIONS: Resistance assumptions
      used in published studies have a strong influence on the projected impact of
      PrEP. Modelers and virologists should collaborate toward clarifying the set of
      resistance assumptions biologically relevant to the PrEP products which are
      already in use or soon to be added to the arsenal against HIV.

PMID- 24282560
TI  - Effects of forest age on soil autotrophic and heterotrophic respiration differ
      between evergreen and deciduous forests.
AB  - We examined the effects of forest stand age on soil respiration (SR) including
      the heterotrophic respiration (HR) and autotrophic respiration (AR) of two forest
      types. We measured soil respiration and partitioned the HR and AR components
      across three age classes ~15, ~25, and ~35-year-old Pinus sylvestris var.
      mongolica (Mongolia pine) and Larix principis-rupprechtii (larch) in a forest
      steppe ecotone, northern China (June 2006 to October 2009). We analyzed the
      relationship between seasonal dynamics of SR, HR, AR and soil temperature (ST),
      soil water content (SWC) and normalized difference vegetation index (NDVI, a
      plant greenness and net primary productivity indicator). Our results showed that
      ST and SWC were driving factors for the seasonal dynamics of SR rather than plant
      greenness, irrespective of stand age and forest type. For ~15-year-old stands,
      the seasonal dynamics of both AR and HR were dependent on ST. Higher Q10 of HR
      compared with AR occurred in larch. However, in Mongolia pine a similar Q10
      occurred between HR and AR. With stand age, Q10 of both HR and AR increased in
      larch. For Mongolia pine, Q10 of HR increased with stand age, but AR showed no
      significant relationship with ST. As stand age increased, HR was correlated with
      SWC in Mongolia pine, but for larch AR correlated with SWC. The dependence of AR
      on NDVI occurred in ~35-year-old Mongolia pine. Our study demonstrated the
      importance of separating autotrophic and heterotrophic respiration components of
      SR when stimulating the response of soil carbon efflux to environmental changes.
      When estimating the response of autotrophic and heterotrophic respiration to
      environmental changes, the effect of forest type on age-related trends is
      required.

PMID- 24282561
TI  - Mycobacterial phosphatidylinositol mannoside 6 (PIM6) up-regulates TCR-triggered
      HIV-1 replication in CD4+ T cells.
AB  - Tuberculosis (TB) is the leading cause of mortality among those infected with
      human immunodeficiency virus (HIV-1) worldwide. HIV-1 load and heterogeneity are
      increased both locally and systemically in active TB. Mycobacterium tuberculosis
      (MTB) infection supports HIV-1 replication through dysregulation of host
      cytokines, chemokines, and their receptors. However the possibility that
      mycobacterial molecules released from MTB infected macrophages directly interact
      with CD4(+) T cells triggering HIV-1 replication has not been fully explored. We
      studied the direct effect of different MTB molecules on HIV-1 replication (R5
      tropic strain Bal) in anti-CD3- stimulated CD4(+) T cells from healthy donors in
      an antigen presenting cell (APC)-free system. PIM6, a major glycolipid of the
      mycobacterial cell wall, induced significant increases in the percent of HIV-1
      infected T cells and the viral production in culture supernatants. In spite of
      structural relatedness, none of the other three major MTB cell wall glycolipids
      had significant impact on HIV-1 replication in T cells. Increased levels of IFN
      gamma in culture supernatants from cells treated with PIM6 indicate that HIV-1
      replication is likely dependent on enhanced T cell activation. In HEK293 cells
      transfected with TLR2, PIM6 was the strongest TLR2 agonist among the cell wall
      associated glycolipids tested. PIM6 increased the percentage of HIV infected
      cells and viral particles in the supernatant in a T-cell-based reporter cell line
      (JLTRg-R5) transfected with TLR1 and TLR2 but not in the cells transfected with
      the empty vector (which lack TLR2 expression) confirming that PIM6-induced HIV-1
      replication depends at least partially on TLR2 signaling. 

PMID- 24282562
TI  - Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of
      chronically infected patients.
AB  - Chronic HIV-1 infection is associated with persistent viremia in most patients,
      but it remains unclear how free virus may survive the potential hostile effects
      of plasma. We investigated whether sites might exist on the surfaces of
      circulating blood cells for protection of infectious HIV-1 particles. Red blood
      cells (RBC) either from blood of uninfected normal individuals, or from blood
      obtained without EDTA from chronically infected HIV-1 patients, invariably
      contained a small number of RBC having attached platelets as determined by flow
      cytometry, light microscopy, and immunofluorescence microscopy. After mixing
      normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and
      complexes of platelets attached to RBC were purified by fluorescence-activated
      cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed
      by washing and co-incubation with CD4-positive peripheral blood mononuclear cells
      (PBMC), platelets, and platelet-RBC complexes, but not platelet-free RBC, caused
      infection of PBMC. Infection was prevented by pre-treating the platelet-RBC
      complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture) from
      chronically infected patients with low viral loads were also co-incubated with
      PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated
      plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant,
      were noninfectious. Interestingly, the RBC from most of the patients caused cell
      cell infection of PBMC that was prevented by stripping the RBC with EDTA. A
      monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of
      PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a)
      platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although
      containing viral RNA, is an environment that lacks detectable infectious HIV-1;
      (b) platelets and platelet-RBC complexes, but not purified RBC, bind infectious
      HIV-1; (c) DC-SIGN, and possibly other C-type lectins, may represent binding
      sites for infectious HIV-1 on platelets and platelet-RBC complexes. 

PMID- 24282563
TI  - Use of stable isotopes to investigate keratin deposition in the claw tips of
      ducks.
AB  - Stable isotopes derived from the claws of birds could be used to determine the
      migratory origins of birds if the time periods represented in excised sections of
      claws were known. We investigated new keratin growth in the claws of adult female
      Lesser Scaup (Aythya affinis) by estimating the equilibration rates of stable
      isotopes (delta (13)C, delta (15)N, and delta (2)H) from the breeding grounds
      into 1 mm claw tips. We sampled birds on their breeding ground through time and
      found that it took approximately 3-3.5 months for isotope values in most claw
      tips to equilibrate to isotope values that reflected those present in the
      environment on their breeding grounds. Results from this study suggest that
      isotopes equilibrate slowly into claw tips of Lesser Scaup, suggesting isotopes
      could potentially be used to determine the wintering grounds of birds. We suggest
      using controlled feeding experiments or longitudinal field investigations to
      understand claw growth and isotopic equilibration in claw tips. Such information
      would be valuable in ascertaining whether claw tips can be used in future studies
      to identify the migratory origins of birds. 

PMID- 24282564
TI  - Extreme evolutionary conservation of functionally important regions in H1N1
      influenza proteome.
AB  - The H1N1 subtype of influenza A virus has caused two of the four documented
      pandemics and is responsible for seasonal epidemic outbreaks, presenting a
      continuous threat to public health. Co-circulating antigenically divergent
      influenza strains significantly complicates vaccine development and use. Here, by
      combining evolutionary, structural, functional, and population information about
      the H1N1 proteome, we seek to answer two questions: (1) do residues on the
      protein surfaces evolve faster than the protein core residues consistently across
      all proteins that constitute the influenza proteome? and (2) in spite of the
      rapid evolution of surface residues in influenza proteins, are there any protein
      regions on the protein surface that do not evolve? To answer these questions, we
      first built phylogenetically-aware models of the patterns of surface and interior
      substitutions. Employing these models, we found a single coherent pattern of
      faster evolution on the protein surfaces that characterizes all influenza
      proteins. The pattern is consistent with the events of inter-species
      reassortment, the worldwide introduction of the flu vaccine in the early 80's, as
      well as the differences caused by the geographic origins of the virus. Next, we
      developed an automated computational pipeline to comprehensively detect regions
      of the protein surface residues that were 100% conserved over multiple years and
      in multiple host species. We identified conserved regions on the surface of 10
      influenza proteins spread across all avian, swine, and human strains; with the
      exception of a small group of isolated strains that affected the conservation of
      three proteins. Surprisingly, these regions were also unaffected by genetic
      variation in the pandemic 2009 H1N1 viral population data obtained from deep
      sequencing experiments. Finally, the conserved regions were intrinsically related
      to the intra-viral macromolecular interaction interfaces. Our study may provide
      further insights towards the identification of novel protein targets for
      influenza antivirals. 

PMID- 24282565
TI  - Reaching the unreachable: providing STI control services to female sex workers
      via mobile team outreach.
AB  - BACKGROUND: As part of a community-randomized trial of a multicomponent
      intervention to prevent sexually transmitted infections, we created Mobile Teams
      (MTs) in ten intervention cities across Peru to improve outreach to female sex
      workers (FSW) for strengthened STI prevention services. METHODS: Throughout 20
      two-month cycles, MTs provided counseling; condoms; screening and specific
      treatment for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and vaginal
      Trichomonas vaginalis (TV) infections; and periodic presumptive metronidazole
      treatment for vaginal infections. RESULTS: MTs had 48,207 separate encounters
      with 24,814 FSW; numbers of sex work venues and of FSW reached increased steadily
      over several cycles. Approximately 50% of FSW reached per cycle were new.
      Reported condom use with last client increased from 73% to 93%. Presumptive
      metronidazole treatment was accepted 83% of times offered. Over 38 months, CT
      prevalence declined from 15.4% to 8.2%, and TV prevalence from 7.3% to 2.6%.
      Among participants in >= 9 cycles, CT prevalence decreased from 12.9% to 6.0% (p
      <0.001); TV from 4.6% to 1.5% (p <0.001); and NG from 0.8% to 0.4% (p = 0.07).
      CONCLUSIONS: Mobile outreach to FSW reached many FSW not utilizing government
      clinics. Self-reported condom use substantially increased; CT and TV prevalences
      declined significantly. The community-randomized trial, reported separately,
      demonstrated significantly greater reductions in composite prevalence of CT, NG,
      TV, or high-titer syphilis serology in FSW in these ten intervention cities than
      in ten matched control cities.

PMID- 24282566
TI  - A systematic review of the relationships between intimate partner violence and
      HIV/AIDS.
AB  - BACKGROUND: Intimate partner violence (IPV) is a significant health problem that
      has been associated with HIV infection in numerous studies. We aimed to
      systematically review the literature on relationships between IPV and HIV in
      order to describe the prevalence of IPV in people with HIV, the prevalence of HIV
      in people experiencing IPV, the association between IPV and HIV, and evidence
      regarding mechanisms of risk and interventions. METHODS: Data sources were 10
      electronic databases and reference lists. Studies were included if they reported
      data on the relationship between IPV and HIV. All records were independently
      reviewed by two authors at the stages of title and abstract review and full text
      review. Any abstract considered eligible by either reviewer was reviewed in full,
      and any disagreement regarding eligibility of full texts or data extracted was
      resolved by discussion. RESULTS: 101 articles were included. Experiencing IPV and
      HIV infection were associated in unadjusted analyses in most studies, as well as
      in adjusted analyses in many studies. The findings of qualitative and
      quantitative studies assessing potential mechanisms linking IPV and HIV were
      variable. Few interventions have been assessed, but two identified in this review
      were promising in terms of preventing IPV, though not HIV infection. CONCLUSIONS:
      Experiencing IPV and HIV infection tend to be associated in unadjusted analyses,
      suggesting that IPV screening and linkage with relevant programs and services may
      be valuable. It is unclear whether there is a causal association between
      experiencing IPV and HIV infection. Research should focus on defining parameters
      of IPV which are relevant to HIV infection, including type of IPV and period of
      exposure and risk, on assessing potential mechanisms, and on developing and
      assessing interventions which build on the strengths of existing studies.

PMID- 24282568
TI  - Prognostic value of cancer stem cell marker aldehyde dehydrogenase in ovarian
      cancer: a meta-analysis.
AB  - OBJECTIVE: Aldehyde dehydrogenase (ALDH) has recently been reported as a marker
      of cancer stem-like cells in ovarian cancer. However, the prognostic role of ALDH
      in ovarian cancer still remains controversial. In this study, we aimed to
      evaluate the association between the expression of ALDH and the outcome of
      ovarian cancer patients by performing a meta-analysis. METHODS: We systematically
      searched for studies investigating the relationships between ALDH expression and
      outcome of ovarian cancer patients. Only articles in which ALDH expression was
      detected by immunohistochemical staining were included. A meta-analysis was
      performed to generate combined hazard ratios (HRs) with 95% confidence intervals
      (CIs) for overall survival (OS) and disease-free survival (DFS). RESULTS: A total
      of 1,258 patients from 7 studies (6 articles) were included in the analysis. Our
      results showed that high ALDH expression in patients with ovarian cancer was
      associated with poor prognosis in terms of Os (HR, 1.25; 95% CI, 1.07-1.47; P =
      0.005) and DFS (HR, 1.58; 95% CI, 1.00-2.49; P = 0.052), though the difference
      for DFS was not statistically significant. In addition, there was no evidence of
      publication bias as suggested by Begg's and Egger's tests (Begg's test, P =
      0.707; Egger's test, P = 0.355). CONCLUSION: The present meta-analysis indicated
      that elevated ALDH expression was associated with poor prognosis in patients with
      ovarian cancer.

PMID- 24282567
TI  - The role of TLR4 896 A>G and 1196 C>T in susceptibility to infections: a review
      and meta-analysis of genetic association studies.
AB  - BACKGROUND: Toll-like receptor 4 plays a role in pathogen recognition, and common
      polymorphisms may alter host susceptibility to infectious diseases. PURPOSE: To
      review the association of two common polymorphisms (TLR4 896A>G and TLR4 1196C>T)
      with infectious diseases. DATA SOURCES: We searched PubMed and EMBASE up to March
      2013 for pertinent literature in English, and complemented search with references
      lists of eligible studies. STUDY SELECTION: We included all studies that:
      reported an infectious outcome; had a case-control design and reported the TLR4
      896A>G and/or TLR4 1196C>T genotype frequencies; 59 studies fulfilled these
      criteria and were analyzed. DATA EXTRACTION: Two authors independently extracted
      study data. DATA SYNTHESIS: The generalized odds ratio metric (ORG) was used to
      quantify the impact of TLR4 variants on disease susceptibility. A meta-analysis
      was undertaken for outcomes reported in >1 study. Eleven of 37 distinct outcomes
      were significant. TLR4 896 A>G increased risk for all parasitic infections (ORG
      1.59; 95%CI 1.05-2.42), malaria (1.31; 95%CI 1.04-1.66), brucellosis (2.66; 95%CI
      1.66-4.27), cutaneous leishmaniasis (7.22; 95%CI 1.91-27.29), neurocysticercosis
      (4.39; 95%CI 2.53-7.61), Streptococcus pyogenes tonsillar disease (2.93; 95%CI
      1.24-6.93) , typhoid fever (2.51; 95%CI 1.18-5.34) and adult urinary tract
      infections (1.98; 95%CI 1.04-3.98), but was protective for leprosy (0.36; 95%CI
      0.22-0.60). TLR4 1196 C>T effects were similar to TLR4 896 A>G for brucellosis,
      cutaneous leishmaniasis, leprosy, typhoid fever and S. pyogenes tonsillar
      disease, and was protective for bacterial vaginosis in pregnancy (0.55; 95%CI
      0.31-0.98) and Haemophilus influenzae tonsillar disease (0.42; 95%CI 0.17-1.00).
      The majority of significant associations were among predominantly Asian
      populations and significant associations were rare among European populations.
      CONCLUSIONS: Depending on the type of infection and population, TLR4
      polymorphisms are associated with increased, decreased or no difference in
      infectious disease. This may be due to differential functional expression of
      TLR4, the co-segregation of TLR4 variants or a favorable inflammatory response.

PMID- 24282569
TI  - Dissection of the TssB-TssC interface during type VI secretion sheath complex
      formation.
AB  - The Type VI secretion system (T6SS) is a versatile machine that delivers toxins
      into either eukaryotic or bacterial cells. At a molecular level, the T6SS is
      composed of a membrane complex that anchors a long cytoplasmic tubular structure
      to the cell envelope. This structure is thought to resemble the tail of
      contractile bacteriophages. It is composed of the Hcp protein that assembles into
      hexameric rings stacked onto each other to form a tube similar to the phage tail
      tube. This tube is proposed to be wrapped by a structure called the sheath,
      composed of two proteins, TssB and TssC. It has been shown using fluorescence
      microscopy that the TssB and TssC proteins assemble into a tubular structure that
      cycles between long and short conformations suggesting that, similarly to the
      bacteriophage sheath, the T6SS sheath undergoes elongation and contraction
      events. The TssB and TssC proteins have been shown to interact and a specific
      alpha-helix of TssB is required for this interaction. Here, we confirm that the
      TssB and TssC proteins interact in enteroaggregative E. coli. We further show
      that this interaction requires the N-terminal region of TssC and the conserved
      alpha-helix of TssB. Using site-directed mutagenesis coupled to phenotypic
      analyses, we demonstrate that an hydrophobic motif located in the N-terminal
      region of this helix is required for interaction with TssC, sheath assembly and
      T6SS function. 

PMID- 24282570
TI  - Deciphering the combinatorial roles of geometric, mechanical, and adhesion cues
      in regulation of cell spreading.
AB  - Significant effort has gone towards parsing out the effects of surrounding
      microenvironment on macroscopic behavior of stem cells. Many of the
      microenvironmental cues, however, are intertwined, and thus, further studies are
      warranted to identify the intricate interplay among the conflicting downstream
      signaling pathways that ultimately guide a cell response. In this contribution,
      by patterning adhesive PEG (polyethylene glycol) hydrogels using Dip Pen
      Nanolithography (DPN), we demonstrate that substrate elasticity, subcellular
      elasticity, ligand density, and topography ultimately define mesenchymal stem
      cells (MSCs) spreading and shape. Physical characteristics are parsed
      individually with 7 kilopascal (kPa) hydrogel islands leading to smaller, spindle
      shaped cells and 105 kPa hydrogel islands leading to larger, polygonal cell
      shapes. In a parallel effort, a finite element model was constructed to
      characterize and confirm experimental findings and aid as a predictive tool in
      modeling cell microenvironments. Signaling pathway inhibition studies suggested
      that RhoA is a key regulator of cell response to the cooperative effect of the
      tunable substrate variables. These results are significant for the engineering of
      cell-extra cellular matrix interfaces and ultimately decoupling matrix bound cues
      presented to cells in a tissue microenvironment for regenerative medicine. 

PMID- 24282571
TI  - Cyclic phosphatidic acid stimulates cAMP production and inhibits growth in human
      colon cancer cells.
AB  - Colon cancer is a malignancy that develops in colon and rectal tissues. The
      prognosis for metastatic colon cancer remains poor, and novel therapeutic options
      are required to reduce colon cancer mortality. Recently, intracellular cAMP
      levels have been suggested to influence the behavior of cancer cells.
      Intriguingly, cyclic phosphatidic acid (cPA) and its structural analogs inhibit
      growth in many cancer cell lines, and our previous work has suggested that cPA
      increases cAMP production. Phosphodiesterase (PDE) type 3 isoforms PDE3A and
      PDE3B are expressed mainly in cardiovascular tissue and adipose tissue,
      respectively. Moreover, increase in intracellular cAMP levels has been associated
      with the inhibition of growth in colon cancer cells. These findings suggest that
      cPA could be used in colon cancer therapy. In this study, we found that cPA
      inhibited the growth of HT-29 cells, which express high levels of PDE3B, but not
      the growth of DLD-1 cells, which express low levels of PDE3B. Furthermore, cPA
      inhibited the phosphorylation of Akt in HT-29 cells in a dose-dependent fashion.
      Our results suggest that PDE3B expression and intracellular cAMP levels are
      correlated with the proliferation of colon cancer cells. These findings
      demonstrate for the first time that cPA may serve as a useful a molecule in
      targeted therapy for colon cancer. 

PMID- 24282573
TI  - Influence of material properties on TiO2 nanoparticle agglomeration.
AB  - Emerging nanomaterials are being manufactured with varying particle sizes,
      morphologies, and crystal structures in the pursuit of achieving outstanding
      functional properties. These variations in these key material properties of
      nanoparticles may affect their environmental fate and transport. To date, few
      studies have investigated this important aspect of nanoparticles' environmental
      behavior. In this study, the aggregation kinetics of ten different TiO2
      nanoparticles (5 anatase and 5 rutile each with varying size) was systematically
      evaluated. Our results show that, as particle size increases, the surface charge
      of both anatase and rutile TiO2 nanoparticles shifts toward a more negative
      value, and, accordingly, the point of zero charge shifts toward a lower value.
      The colloidal stability of anatase sphere samples agreed well with DLVO
      theoretical predictions, where an increase in particle size led to a higher
      energy barrier and therefore greater critical coagulation concentration. In
      contrast, the critical coagulation concentration of rutile rod samples correlated
      positively with the specific surface area, i.e., samples with higher specific
      surface area exhibited higher stability. Finally, due to the large innate
      negative surface charge of all the TiO2 samples at the pH value (pH = 8) tested,
      the addition of natural organic matter was observed to have minimal effect on
      TiO2 aggregation kinetics, except for the smallest rutile rods that showed
      decreased stability in the presence of natural organic matter.

PMID- 24282572
TI  - Feeding low or pharmacological concentrations of zinc oxide changes the hepatic
      proteome profiles in weaned piglets.
AB  - Pharmacological levels of zinc oxide can promote growth and health of weaning
      piglets, but the underlying molecular mechanisms are yet not fully understood.
      The aim of this study was to determine changes in the global hepatic protein
      expression in response to dietary zinc oxide in weaned piglets. Nine half-sib
      piglets were allocated to three dietary zinc treatment groups (50, 150, 2500
      mg/kg dry matter). After 14 d, pigs were euthanized and liver samples taken. The
      increase in hepatic zinc concentration following dietary supplementation of zinc
      was accompanied by up-regulation of metallothionein mRNA and protein expression.
      Global hepatic protein profiles were obtained by two-dimensional difference gel
      electrophoresis following matrix-assisted laser desorption ionization/time-of
      flight mass spectrometry. A total of 15 proteins were differentially (P<0.05)
      expressed between groups receiving control (150 mg/kg) or pharmacological levels
      of zinc (2500 mg/kg) with 7 down- (e.g. arginase1, thiosulfate sulfurtransferase,
      HSP70) and 8 up-regulated (e.g. apolipoprotein AI, transferrin, C1
      tetrahydrofolate synthase) proteins. Additionally, three proteins were
      differentially expressed with low zinc supply (50 mg/kg Zn) in comparison to the
      control diet. The identified proteins were mainly associated with functions
      related to cellular stress, transport, metabolism, and signal transduction. The
      differential regulation was evaluated at the mRNA level and a subset of three
      proteins of different functional groups was selected for confirmation by western
      blotting. The results of this proteomic study suggest that zinc affects important
      liver functions such as blood protein secretion, protein metabolism,
      detoxification and redox homeostasis, thus supporting the hypothesis of
      intermediary effects of pharmacological levels of zinc oxide fed to pigs. 

PMID- 24282575
TI  - Population dynamics and diet of the madamango Sea catfish Cathorops spixii
      (Agassiz, 1829) (Siluriformes: Ariidae) in a tropical bight in Southeastern
      Brazil.
AB  - The madamango sea catfish, Cathorops spixii (Siluriformes: Ariidae), is often
      among the most abundant fishes on the South American Atlantic coast. In the
      present study, conducted in shallow, non-estuarine coastal areas of Caraguatatuba
      Bight in southeastern Brazil, collections of this species, the most abundant
      member of the ichthyofauna, included primarily medium-sized individuals,
      indicating that the area may play a specific role in their development. Although
      studies of the local ichthyofauna have been much neglected, the area is
      economically important and its ecological significance is undervalued. This study
      primarily treats habitat use by C. spixii, assessing certain population
      parameters and the dietary composition. Monthly samples were taken from August
      2003 through October 2004, with three trawls in two areas, corresponding to
      depths of about 1 to 4 m. The catfish showed two main peaks of abundance in the
      area, in April/May and July 2004. A mode around 9 cm SL persisted through time,
      and the entrance of younger recruits peaked from January to April. The low
      estimate for body-growth parameters (K = 0.16) corroborates some K-strategist
      characteristics of the species. The asymptotic length was 27.3 cm SL and total
      mortality (Z) was 1.01 yr(-1). Cathorops spixii showed an omnivorous feeding
      habit, preying mainly upon polychaetes, copepods and bivalves, with considerable
      seasonality in its diet.

PMID- 24282574
TI  - Long-term exercise is a potent trigger for DeltaFosB induction in the hippocampus
      along the dorso-ventral axis.
AB  - Physical exercise improves multiple aspects of hippocampal function. In line with
      the notion that neuronal activity is key to promoting neuronal functions,
      previous literature has consistently demonstrated that acute bouts of exercise
      evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to
      an accumulation of the transcription factor DeltaFosB, which mediates long-term
      neural plasticity. In this study, we tested the hypothesis that long-term
      voluntary wheel running induces DeltaFosB expression in the hippocampus, and
      examined any potential region-specific effects within the hippocampal subfields
      along the dorso-ventral axis. Male C57BL/6 mice were housed with or without a
      running wheel for 4 weeks. Long-term wheel running significantly increased
      FosB/DeltaFosB immunoreactivity in all hippocampal regions measured (i.e., in the
      DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results
      confirmed that wheel running induced region-specific expression of FosB/DeltaFosB
      immunoreactivity in the cortex, suggesting that the uniform increase in
      FosB/DeltaFosB within the hippocampus is not a non-specific consequence of
      running. Western blot data indicated that the increased hippocampal
      FosB/DeltaFosB immunoreactivity was primarily due to increased DeltaFosB. These
      results suggest that long-term physical exercise is a potent trigger for
      DeltaFosB induction throughout the entire hippocampus, which would explain why
      exercise can improve both dorsal and ventral hippocampus-dependent functions.
      Interestingly, we found that FosB/DeltaFosB expression in the DG was positively
      correlated with the number of doublecortin-immunoreactive (i.e., immature)
      neurons. Although the mechanisms by which DeltaFosB mediates exercise-induced
      neurogenesis are still uncertain, these data imply that exercise-induced
      neurogenesis is at least activity dependent. Taken together, our current results
      suggest that DeltaFosB is a new molecular target involved in regulating exercise
      induced hippocampal plasticity. 

PMID- 24282576
TI  - Prevalence and risk factors of poor sleep quality among Chinese elderly in an
      urban community: results from the Shanghai aging study.
AB  - BACKGROUND: Sleep disorders causes a significant negative effect on mental and
      physical health, particularly among the elderly. The disease burden and risk
      factors of poor sleep quality of the elderly need to be verified using a
      validated form of measurement in urban mainland China. METHODS: This study
      included 1086 community residents aged >= 60 years who completed the Chinese
      version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleeper was defined
      by a CPSQI global score of >5. Subjects also accepted the neurological and
      neuropsychological assessments, including the Mini-Mental State Examination,
      Center for Epidemiological Studies Depression Scale, and Zung Self-Rating Anxiety
      Scale (ZSAS). A history of chronic diseases was confirmed by the medical records
      of each participant. RESULTS: The prevalence of poor sleep quality in this
      population was 41.5% (95% confidence interval (CI) = 38.6-44.5%), with a higher
      rate observed in elderly females (45.8% [95% CI = 41.9-49.7%]) than that in
      elderly males (35.8% [95% CI = 31.4-40.1%]). The prevalence rate increased with
      age, from 32.1% (95% CI = 27.8-36.4%) in those aged 60-69 years to 52.5% (95% CI
      = 45.9-59.1%) in those aged >= 80 years (p value for trend<0.001). Multivariate
      logistic regression analysis indicated that age (OR = 1.03[95% CI = 1.01-1.05],
      p<0.001), less education duration (OR = 1.04 [95% CI = 1.01-1.08, p = 0.014),
      living alone (OR = 1.62 [95% CI = 1.02-2.58], p = 0.04), anxiety (ZSAS score: OR
      = 1.09 [95% CI = 1.05-1.12], p<0.001), number of chronic disease (OR = 1.18 [95%
      CI = 1.07-1.30], p = 0.14) and arthritis (OR = 1.45[95% CI = 1.05-2.01], p =
      0.025) were risk factors of poor sleep quality. CONCLUSIONS: Poor sleep quality
      is highly prevalent among elderly Chinese residents in urban Shanghai. Growing
      attention and comprehensive countermeasures involving psycho-social and personal
      activities might alleviate the sleep problem in the elderly.

PMID- 24282577
TI  - You do the math: coding of bets and outcomes in a gambling task in the feedback
      related negativity and p300 in healthy adults.
AB  - The feedback-related negativity (FRN) is an event-related potential (ERP)
      component associated with processing of performance feedback, with more negative
      amplitudes for losses relative to wins. The amplitude of the FRN following near
      misses, i.e. the experience of coming close to winning, is between the amplitude
      elicited by losses and wins. In gambling, however, outcome value may not always
      be obvious since initially placed bets need to be taken into account when
      evaluating wins or losses. It is still unclear if initial bet size is reflected
      in the FRN or the later P300 component. The present study applied a virtual card
      gambling task to investigate the sensitivity of FRN and P300 to the manipulation
      of outcome magnitude as implemented through the presence or absence of initial
      bets, resulting in wins, losses or ambivalent outcomes, with the latter
      representing losses with and wins without bets. The FRN was larger for trials
      with bets compared to trials without bets. Wins were associated with a smaller
      FRN than losses or ambivalent outcomes, while losses and ambivalent outcomes did
      not differ. P300 amplitudes were larger for trials without bets, and wins were
      associated with a larger P300 than losses or ambivalent outcomes. Crucially, P300
      amplitudes were also smaller for ambivalent outcomes compared to losses. Thus,
      the different dimensions determining outcome value appear to be integrated in
      early and late stages of feedback processing. However, only at later stages
      reflected in the P300 were ambivalent outcomes with and without bet clearly
      distinguished from other outcomes. 

PMID- 24282578
TI  - Impacts of population structure and analytical models in genome-wide association
      studies of complex traits in forest trees: a case study in Eucalyptus globulus.
AB  - The promise of association genetics to identify genes or genomic regions
      controlling complex traits has generated a flurry of interest. Such phenotype
      genotype associations could be useful to accelerate tree breeding cycles,
      increase precision and selection intensity for late expressing, low heritability
      traits. However, the prospects of association genetics in highly heterozygous
      undomesticated forest trees can be severely impacted by the presence of cryptic
      population and pedigree structure. To investigate how to better account for this,
      we compared the GLM and five combinations of the Unified Mixed Model ( UMM ) on
      data of a low-density genome-wide association study for growth and wood property
      traits carried out in a Eucalyptus globulus population (n = 303) with 7,680
      Diversity Array Technology (DArT) markers. Model comparisons were based on the
      degree of deviation from the uniform distribution and estimates of the mean
      square differences between the observed and expected p-values of all significant
      marker-trait associations detected. Our analysis revealed the presence of
      population and family structure. There was not a single best model for all
      traits. Striking differences in detection power and accuracy were observed among
      the different models especially when population structure was not accounted for.
      The UMM method was the best and produced superior results when compared to GLM
      for all traits. Following stringent correction for false discoveries, 18 marker
      trait associations were detected, 16 for tree diameter growth and two for lignin
      monomer composition (S:G ratio), a key wood property trait. The two DArT markers
      associated with S:G ratio on chromosome 10, physically map within 1 Mbp of the
      ferulate 5-hydroxylase (F5H) gene, providing a putative independent validation of
      this marker-trait association. This study details the merit of collectively
      integrate population structure and relatedness in association analyses in
      undomesticated, highly heterozygous forest trees, and provides additional
      insights into the nature of complex quantitative traits in Eucalyptus.

PMID- 24282579
TI  - Breed-specific hematological phenotypes in the dog: a natural resource for the
      genetic dissection of hematological parameters in a mammalian species.
AB  - Remarkably little has been published on hematological phenotypes of the domestic
      dog, the most polymorphic species on the planet. Information on the signalment
      and complete blood cell count of all dogs with normal red and white blood cell
      parameters judged by existing reference intervals was extracted from a veterinary
      database. Normal hematological profiles were available for 6046 dogs, 5447 of
      which also had machine platelet concentrations within the reference interval.
      Seventy-five pure breeds plus a mixed breed control group were represented by 10
      or more dogs. All measured parameters except mean corpuscular hemoglobin
      concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs),
      neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood
      cell parameters, all varied with sex. Neutering status had an impact on
      hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and
      concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets.
      Principal component analysis of hematological data revealed 37 pure breeds with
      distinctive phenotypes. Furthermore, all hematological parameters except MCHC
      showed significant differences between specific individual breeds and the mixed
      breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this
      way, of which 19 had already been identified by principal component analysis.
      Tentative breed-specific reference intervals were generated for breeds with a
      distinctive phenotype identified by comparative analysis. This study represents
      the first large-scale analysis of hematological phenotypes in the dog and
      underlines the important potential of this species in the elucidation of genetic
      determinants of hematological traits, triangulating phenotype, breed and genetic
      predisposition. 

PMID- 24282580
TI  - Drivers of wetland conversion: a global meta-analysis.
AB  - Meta-analysis of case studies has become an important tool for synthesizing case
      study findings in land change. Meta-analyses of deforestation, urbanization,
      desertification and change in shifting cultivation systems have been published.
      This present study adds to this literature, with an analysis of the proximate
      causes and underlying forces of wetland conversion at a global scale using two
      complementary approaches of systematic review. Firstly, a meta-analysis of 105
      case-study papers describing wetland conversion was performed, showing that
      different combinations of multiple-factor proximate causes, and underlying
      forces, drive wetland conversion. Agricultural development has been the main
      proximate cause of wetland conversion, and economic growth and population density
      are the most frequently identified underlying forces. Secondly, to add a more
      quantitative component to the study, a logistic meta-regression analysis was
      performed to estimate the likelihood of wetland conversion worldwide, using
      globally-consistent biophysical and socioeconomic location factor maps.
      Significant factors explaining wetland conversion, in order of importance, are
      market influence, total wetland area (lower conversion probability), mean annual
      temperature and cropland or built-up area. The regression analyses results
      support the outcomes of the meta-analysis of the processes of conversion
      mentioned in the individual case studies. In other meta-analyses of land change,
      similar factors (e.g., agricultural development, population growth,
      market/economic factors) are also identified as important causes of various types
      of land change (e.g., deforestation, desertification). Meta-analysis helps to
      identify commonalities across the various local case studies and identify which
      variables may lead to individual cases to behave differently. The meta-regression
      provides maps indicating the likelihood of wetland conversion worldwide based on
      the location factors that have determined historic conversions. 

PMID- 24282581
TI  - Assessment of iodine status in children, adults, pregnant women and lactating
      women in iodine-replete areas of China.
AB  - BACKGROUND: Iodine deficiency disorders (IDD) are widespread in China. Presently,
      IDD have been put under control by Universal Salt Iodisation (USI) in China;
      however, there is a lack of evidence on whether the iodine status in adults,
      pregnant women and lactating women is optimal. This study was therefore conducted
      to assess the iodine nutrition and thyroid function of children, adults, pregnant
      women and lactating women residing in areas where the USI program is fully
      established. DESIGN: Six areas were selected according to the geographical
      regions in China. In each of these areas, we selected 4 distinct groups of
      subjects (children, adults, pregnant women and lactating women) in regions where
      the coverage rate of iodised salt was more than 95% and the levels of iodine and
      fluoride in drinking water were less than or equal to 10 ug/L and 1 mg/L,
      respectively. We tested the iodine content of salt, urinary iodine (UI), free
      thyroxin (FT4), thyrotropin (TSH), thyroglobulin (Tg), thyroglobulin antibody (Tg
      Ab) and antimicrosomal antibody (TM-Ab) in the 4 groups, and examined the thyroid
      volume in children. RESULTS: The median urinary iodine (MUI) concentrations were
      271.4 MUg/L, 260.2 MUg/L, 205.9 MUg/L and 193.9 MUg/L in children, adults,
      pregnant women and lactating women, respectively; MUI in children and adults were
      more than adequate. The goitre prevalence (GP) in children was 6.70%. The odds
      ratios (OR) of subclinical hypothyroidism in the Tg-Ab- or TM-Ab-positive groups
      were 3.80, 7.65, 2.01 and 7.47 for children, adults, pregnant women and lactating
      women, respectively, compared with the negative groups. CONCLUSIONS: The iodine
      status in children and adults is above the requirement, we should reduce their
      iodine intake. Subclinical hypothyroidism easily occurs in the Tg-Ab or TM-Ab
      positive groups.

PMID- 24282582
TI  - In vitro evaluation of the risk of inducing bacterial resistance to disinfection
      treatment with photolysis of hydrogen peroxide.
AB  - The purpose of the present study was to evaluate the risk of inducing bacterial
      resistance to disinfection treatment with photolysis of H2O2 and comparing this
      with existing antibacterial agents. We tested seven antibacterial agents,
      including amoxicillin, cefepime hydrochloride, erythromycin, ofloxacin,
      clindamycin hydrochloride, ciprofloxacin hydrochloride, and minocycline
      hydrochloride, as positive controls for validation of the assay protocol. For all
      of the agents tested, at least one of the four bacterial species (Staphylococcus
      aureus, Enterococcus faecalis, Escherichia coli, and Streptococcus salivarius)
      was resistant to these agents by repeated exposure to subinhibitory
      concentrations of the agents up to 10 times. In contrast, antibacterial activity
      against any of the bacterial species tested (S. aureus, E. faecalis, E. coli, S.
      salivarius, Pseudomonas aeruginosa, Streptococcus mutans, and Aggregatibacter
      actinomycetemcomitans) was not affected by repeated exposure to the disinfection
      treatment up to 40 times. This finding suggested that the risk of inducing
      bacterial resistance by disinfection treatment was low. The active ingredient of
      this disinfection treatment is hydroxyl radicals generated by photolysis of H2O2.
      Therefore, hydroxyl radicals interact with several cell structures and different
      metabolic pathways in microbial cells, probably resulting in a lack of
      development of bacterial resistance. In conclusion, disinfection treatment with
      photolysis of H2O2 appears to be a potential alternative for existing
      antimicrobial agents in terms of a low risk of inducing bacterial resistance. 

PMID- 24282583
TI  - Structural determinants for protein adsorption/non-adsorption to silica surface.
AB  - The understanding of the mechanisms involved in the interaction of proteins with
      inorganic surfaces is of major interest in both fundamental research and
      applications such as nanotechnology. However, despite intense research, the
      mechanisms and the structural determinants of protein/surface interactions are
      still unclear. We developed a strategy consisting in identifying, in a mixture of
      hundreds of soluble proteins, those proteins that are adsorbed on the surface and
      those that are not. If the two protein subsets are large enough, their
      statistical comparative analysis must reveal the physicochemical determinants
      relevant for adsorption versus non-adsorption. This methodology was tested with
      silica nanoparticles. We found that the adsorbed proteins contain a higher number
      of charged amino acids, particularly arginine, which is consistent with
      involvement of this basic amino acid in electrostatic interactions with silica.
      The analysis also identified a marked bias toward low aromatic amino acid content
      (phenylalanine, tryptophan, tyrosine and histidine) in adsorbed proteins.
      Structural analyses and molecular dynamics simulations of proteins from the two
      groups indicate that non-adsorbed proteins have twice as many pi-pi interactions
      and higher structural rigidity. The data are consistent with the notion that
      adsorption is correlated with the flexibility of the protein and with its ability
      to spread on the surface. Our findings led us to propose a refined model of
      protein adsorption. 

PMID- 24282584
TI  - Thermal carrying capacity for a thermally-sensitive species at the warmest edge
      of its range.
AB  - Anthropogenic environmental change is causing unprecedented rates of population
      extirpation and altering the setting of range limits for many species.
      Significant population declines may occur however before any reduction in range
      is observed. Determining and modelling the factors driving population size and
      trends is consequently critical to predict trajectories of change and future
      extinction risk. We tracked during 12 years 51 populations of a cold-water fish
      species (brown trout Salmo trutta) living along a temperature gradient at the
      warmest thermal edge of its range. We developed a carrying capacity model in
      which maximum population size is limited by physical habitat conditions and
      regulated through territoriality. We first tested whether population numbers were
      driven by carrying capacity dynamics and then targeted on establishing (1) the
      temperature thresholds beyond which population numbers switch from being physical
      habitat- to temperature-limited; and (2) the rate at which carrying capacity
      declines with temperature within limiting thermal ranges. Carrying capacity along
      with emergent density-dependent responses explained up to 76% of spatio-temporal
      density variability of juveniles and adults but only 50% of young-of-the-year's.
      By contrast, young-of-the-year trout were highly sensitive to thermal conditions,
      their performance declining with temperature at a higher rate than older life
      stages, and disruptions being triggered at lower temperature thresholds. Results
      suggest that limiting temperature effects were progressively stronger with
      increasing anthropogenic disturbance. There was however a critical threshold,
      matching the incipient thermal limit for survival, beyond which realized density
      was always below potential numbers irrespective of disturbance intensity. We
      additionally found a lower threshold, matching the thermal limit for feeding,
      beyond which even unaltered populations declined. We predict that most of our
      study populations may become extinct by 2100, depicting the gloomy fate of
      thermally-sensitive species occurring at thermal range margins under limited
      potential for adaptation and dispersal. 

PMID- 24282585
TI  - Landscape-scale disturbances modified bird community dynamics in successional
      forest environment.
AB  - Ecosystem-based forest management strives to develop silvicultural practices that
      best emulate natural disturbances such as wildfire to conserve biodiversity
      representative of natural forest ecosystems. Yet, current logging practices alter
      forest structure and reduce the proportion of old-growth forest and,
      consequently, can exert long-term effects on the dynamics of forest biota. The
      stand- and landscape-scale factors driving bird community dynamics in post
      disturbance environment remain poorly understood. In this study, we examined bird
      community dynamics along successional gradients in boreal ecosystems originating
      from fire and logging in landscapes dominated by old-growth forest. We tested if
      bird species richness and community compositions in clear-cutting stands became
      comparable to those in natural stands after 70 years, and identified the relative
      contributions of stand- and landscape-scale forest attributes in bird community
      dynamics. Based on records of bird occurrences at 185 field sites in natural and
      clearcutting stands, we demonstrate that (1) both forest structures and bird
      communities underwent evident changes along successional gradients in post
      clearcutting environment; (2) bird species richness and community composition in
      60- to 70-years-old clearcutting stands still differed from those in 50- to 79
      years-old natural stands, in spite of the fact that most forest attributes of
      clearcutting stands became comparable to those of natural stands after 40 years;
      and (3) landscape disturbances contributed more than stand characteristics in
      explaining the lack of convergence of mature forest species, residents, and short
      distance migrants in post-clearcutting environment. Our study points out that
      more regards should be paid to improve the landscape configuration of the managed
      forests, and implies that old-growth forest retention within logged areas,
      combined with selection cutting and prolonged logging rotations, can better
      emulate fire and alleviate forest harvesting effects on bird community
      assemblages typical of natural boreal ecosystem. 

PMID- 24282586
TI  - Impaired elastin deposition in Fstl1-/- lung allograft under the renal capsule.
AB  - Lung alveolar development in late gestation is a process important to postnatal
      survival. Follistatin-like 1 (Fstl1) is a matricellular protein of the Bmp
      antagonist class, which is involved in the differentiation/maturation of alveolar
      epithelial cells during saccular stage of lung development. This study
      investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent
      secondary septation in the late gestation stage of terminal saccular formation.
      To this aim, we modified the renal capsule allograft model for lung organ culture
      by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic
      host and cultured up to 7 days. The saccular development of the diced lung
      allografts, as indicated by the morphology, epithelial and vascular developments,
      occurred in a manner similar to that in utero. Fstl1 deficiency caused
      atelectatic phenotype companied by impaired epithelial differentiation in D3
      Fstl1(-/-) lung allografts, which is similar to that of E18.5 Fstl1(-/-) lungs,
      supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling
      by intraperitoneal injection of dorsomorphin in the host mice rescued the
      pulmonary atelectasis of D3 Fstl1(-/-) allografts. Furthermore, a marked
      reduction in elastin expression and deposition was observed in walls of air sacs
      of E18.5 Fstl1(-/-) lungs and at the tips of the developing alveolar septae of D7
      Fstl1(-/-) allografts. Thus, in addition to its role on alveolar epithelium,
      Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung
      alveologenesis. Our data demonstrates that the modified renal capsule allograft
      model for lung organ culture is a robust and efficient technique to increase our
      understanding of saccular stage of lung development. 

PMID- 24282587
TI  - Maternal age, parity and isolated birth defects: a population-based case-control
      study in Shenzhen, China.
AB  - BACKGROUND: The etiology of birth defects has been widely studied but is not yet
      fully clarified, previously published data had suggested that maternal age or
      parity maybe involved, but without consistent conclusions. METHODS: A population
      based, case-control study was nested in a cohort of perinatal infants born from
      2010 to 2012 in Baoan District, Shenzhen. Four categories of isolated birth
      defects were defined as cases: congenital heart defects (CHD, n = 693),
      polydactyly (n = 352), cleft lip with or without palate (CL/P, n = 159) and
      equinovarus (n = 119). Controls were non-malformed infants (n = 11,307) randomly
      selected from the same area and period. Odds ratios (ORs) and the 95% confidence
      intervals (CIs) were computed by multivariable unconditional logistic regression
      analysis. RESULTS: Young maternal age (<25 years old) was associated with a
      reduced risk of CHD (adjusted OR = 0.73, 95% CI 0.59-0.90), while with an
      elevated risk of polydactyly (adjusted OR = 1.42, 95% CI 1.09-1.84). Increased
      risk of CL/P-affected pregnancy was observed in mothers older than 35 years old
      (adjusted OR = 2.12, 95% CI 1.26-3.57). Compared to primipara, those having their
      second, and third or more delivery were less likely to have infants with
      equinovarus, with significant adjusted ORs of 0.59 (0.40-0.89) and 0.42 (0.19
      0.93), respectively. CONCLUSION: Maternal age was significantly associated with
      CHD, polydactyly and CL/P relevant pregnancy. Mothers with higher parity might
      have lower risk of equinovarus occurrence in offsprings.

PMID- 24282588
TI  - Establishment of a markerless mutation delivery system in Bacillus subtilis
      stimulated by a double-strand break in the chromosome.
AB  - Bacillus subtilis has been a model for gram-positive bacteria and it has long
      been exploited for industrial and biotechnological applications. However, the
      availability of facile genetic tools for physiological analysis has generally
      lagged substantially behind traditional genetic models such as Escherichia coli
      and Saccharomyces cerevisiae. In this work, we have developed an efficient,
      precise and scarless method for rapid multiple genetic modifications without
      altering the chromosome of B. subtilis. This method employs upp gene as a counter
      selectable marker, double-strand break (DSB) repair caused by exogenous
      endonuclease I-SceI and comK overexpression for fast preparation of competent
      cell. Foreign dsDNA can be simply and efficiently integrated into the chromosome
      by double-crossover homologous recombination. The DSB repair is a potent
      inducement for stimulating the second intramolecular homologous recombination,
      which not only enhances the frequency of resolution by one to two orders of
      magnitude, but also selects for the resolved product. This method has been
      successfully and reiteratively used in B. subtilis to deliver point mutations, to
      generate in-frame deletions, and to construct large-scale deletions. Experimental
      results proved that it allowed repeated use of the selectable marker gene for
      multiple modifications and could be a useful technique for B. subtilis. 

PMID- 24282589
TI  - Preliminary insights into the impact of dietary starch on the ciliate,
      Neobalantidium coli, in captive chimpanzees.
AB  - Infections caused by the intestinal ciliate Neobalantidium coli are asymptomatic
      in most hosts. In humans and captive African great apes clinical infections
      occasionally occur, manifested mainly by dysentery; however, factors responsible
      for development of clinical balantidiasis have not been fully clarified. We
      studied the effect of dietary starch on the intensities of infection by N. coli
      in two groups of captive chimpanzees. Adult chimpanzees infected by N. coli from
      the Hodonin Zoo and from the Brno Zoo, Czech Republic, were fed with a high
      starch diet (HSD) (average 14.7% of starch) for 14 days, followed by a five-day
      transition period and subsequently with a period of low starch diet (LoSD)
      (average 0.1% of starch) for another 14 days. We collected fecal samples during
      the last seven days of HSD and LoSD and fixed them in 10% formalin. We quantified
      trophozoites of N. coli using the FLOTAC method. The numbers of N. coli
      trophozoites were higher during the HSD (mean +/- SD: 49.0 +/- 134.7) than during
      the LoSD (3.5 +/- 6.8). A generalized linear mixed-effects model revealed
      significantly lower numbers of the N. coli trophozoites in the feces during the
      LoSD period in comparison to the HSD period (treatment contrast LoSD vs. HSD: 2.7
      +/- 0.06 (SE), z = 47.7; p<<0.001). We conclude that our data provide a first
      indication that starch-rich diet might be responsible for high intensities of
      infection of N. coli in captive individuals and might predispose them for
      clinically manifested balantidiasis. We discuss the potential nutritional
      modifications to host diets that can be implemented in part to control N. coli
      infections.

PMID- 24282590
TI  - Circulating microRNAs in relation to EGFR status and survival of lung
      adenocarcinoma in female non-smokers.
AB  - OBJECTIVES: Lung adenocarcinoma is considered a unique disease for Asian female
      non-smokers. We investigated whether plasma microRNA (miRNA) expression profiles
      are different by the EGFR status and are associated with survival outcomes of the
      patients. METHODS: Using real-time RT-PCR, we analyzed the expression of 20
      miRNAs in the plasma of 105 female patients with lung adenocarcinoma. Kaplan
      Meier survival analysis and Cox proportional hazards regression were performed to
      determine the association between miRNA expression and overall survival. Time
      dependent receiver operating characteristic (ROC) analysis was also performed.
      RESULTS: In the 20 miRNAs, miR-122 were found differently expressed between wild
      and mutant EGFR carriers (P=0.018). Advanced disease stage and tumor metastasis
      were independently associated with poor prognosis of patients with lung
      adenocarcinoma (P=0.010 and 1.0*10(-4)). Plasma levels of miR-195 and miR-122
      expression were also associated with overall survival in the patients, especially
      in those with advanced stage (HR=0.23, 95%CI:0.07-0.84; and HR=0.22, 95%CI:0.06
      0.77) and EGFR mutation (HR=0.27, 95%CI:0.08-0.96; and HR=0.23, 95%CI=0.06-0.81).
      Moreover, a model including miR-195, miR-122 may predict survival outcomes of
      female patients with lung adenocarcinoma (AUC=0.707). CONCLUSIONS: Circulating
      miR-195 and miR-122 may have prognostic values in predicting the overall survival
      as well as predicting EGFR mutation status in non-smoking female patients with
      lung adenocarcinoma. Measuring plasma levels of miR-195 and miR-122 may
      especially be useful in EGFR mutant patients with lung adenocarcinoma.

PMID- 24282591
TI  - Identification of glucose transporters in Aspergillus nidulans.
AB  - To characterize the mechanisms involved in glucose transport, in the filamentous
      fungus Aspergillus nidulans, we have identified four glucose transporter encoding
      genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the
      Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose,
      fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E
      were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was
      able to restore growth on glucose, fructose, mannose or galactose, indicating
      that these transporters accept multiple sugars as a substrate through an energy
      dependent process. A tenfold excess of unlabeled maltose, galactose, fructose,
      and mannose were able to inhibit glucose uptake to different levels (50 to 80 %)
      in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m
      chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and -E mediate
      glucose transport via active proton symport. The A. nidulans DeltahxtB, DeltahxtC
      or DeltahxtE null mutants showed ~2.5-fold reduction in the affinity for glucose,
      while DeltahxtB and -C also showed a 2-fold reduction in the capacity for glucose
      uptake. The DeltahxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold
      increase in the capacity for glucose uptake. However, only the DeltahxtB mutant
      strain showed a detectable decreased rate of glucose consumption at low
      concentrations and an increased resistance to 2-deoxyglucose. 

PMID- 24282592
TI  - Quail FMO3 gene cloning, tissue expression profiling, polymorphism detection and
      association analysis with fishy taint in eggs.
AB  - Quail eggs comprise a significant and favourable part of table eggs in certain
      countries. Some quail eggs, however, present fishy off-flavor which directly
      influences their quality. It is reported that flavin-containing monooxygenase 3
      (FMO3) is associated with fish-odour trait in human and animal products. FMO3 is
      responsible for the degradation of trimethylamine (TMA) in vivo. Loss-of-function
      mutations in FMO3 gene can result in defective TMA N-oxygenation, giving rise to
      disorder known as "fish-odour syndrome" in human, as well as the fishy off-flavor
      in cow milk and chicken eggs. In order to reveal the genetic factor of fishy
      taint in quail eggs, we cloned the cDNA sequence of quail FMO3 gene, investigated
      FMO3 mRNA expression level in various tissues, detected SNPs in the coding region
      of the gene and conducted association analysis between a mutation and the TMA
      content in quail egg yolks. The 1888 bp cDNA sequence of quail FMO3 gene encoding
      532 amino acids was obtained and characterized. The phylogenetic analysis
      revealed quail FMO3 had a closer relationship with chicken FMO3. The FMO3 mRNA
      was highly expressed in liver and kidney of quail. Nine SNPs were detected in the
      coding sequence of quail FMO3 gene, including a nonsense mutation (Q319X) which
      was significantly associated with the elevated TMA content in quail egg yolks.
      Genotype TT at Q319X mutation loci was sensitive to choline. With addition of
      choline in the feed, the quails with homozygote TT at the Q319X mutation loci
      laid fish-odour eggs, indicating an interaction between genotype and diet. The
      results indicated that Q319X mutation was associated with the fishy off-flavor in
      quail eggs. Identification of the unfavorable allele T of quail FMO3 gene can be
      applied in future quail breeding to eliminate fishy off-flavor trait in quail
      eggs. 

PMID- 24282593
TI  - Associations between white matter microstructure and cognitive performance in old
      and very old age.
AB  - Increasing age is associated with deficits in a wide range of cognitive domains
      as well as with structural brain changes. Recent studies using diffusion tensor
      imaging (DTI) have shown that microstructural integrity of white matter is
      associated with cognitive performance in elderly persons, especially on tests
      that rely on perceptual speed. We used structural equation modeling to
      investigate associations between white matter microstructure and cognitive
      functions in a population-based sample of elderly persons (age >= 60 years), free
      of dementia, stroke, and neurological disorders (n = 253). Participants underwent
      a magnetic resonance imaging scan, from which mean fractional anisotropy (FA) and
      mean diffusivity (MD) of seven white matter tracts were quantified. Cognitive
      functioning was analyzed according to performance in five task domains
      (perceptual speed, episodic memory, semantic memory, letter fluency, and category
      fluency). After controlling for age, FA and MD were exclusively related to
      perceptual speed. When further stratifying the sample into two age groups, the
      associations were reliable in the old-old (>= 78 years) only. This relationship
      between white matter microstructure and perceptual speed remained significant
      after excluding persons in a preclinical dementia phase. The observed pattern of
      results suggests that microstructural white matter integrity may be especially
      important to perceptual speed among very old adults.

PMID- 24282594
TI  - Structural analysis of microRNA-target interaction by sequential seed mutagenesis
      and stem-loop 3' RACE.
AB  - BACKGROUND: As a consequence of recent RNAseq efforts, miRNAomes of diverse
      tissues and species are available. However, most interactions between microRNAs
      and regulated mRNAs are still to be deciphered. While in silico analysis of
      microRNAs results in prediction of hundreds of potential targets, bona-fide
      interactions have to be verified e.g. by luciferase reporter assays using fused
      target sites as well as controls incorporating mutated seed sequences. The aim of
      this study was the development of a straightforward approach for sequential
      mutation of multiple target sites within a given 3' UTR. METHODOLOGY/PRINCIPAL
      FINDINGS: The established protocol is based on Seed Mutagenesis Assembly PCR
      (SMAP) allowing for rapid identification of microRNA target sites. Based on the
      presented approach, we were able to determine the transcription factor NKX3.1 as
      a genuine target of miR-155. The sequential mutagenesis of multiple microRNA
      target sites was examined by miR-29a mediated CASP7 regulation, which revealed
      one of two predicted target sites as the predominant site of interaction. Since
      3' UTR sequences of non-model organisms are either lacking in databases or
      computationally predicted, we developed a Stem-Loop 3' UTR RACE PCR (SLURP) for
      efficient generation of required 3' UTR sequence data. The stem-loop primer
      allows for first strand cDNA synthesis by nested PCR amplification of the 3' UTR.
      Besides other applications, the SLURP method was used to gain data on porcine
      CASP7 3'UTR evaluating evolutionary conservation of the studied interaction.
      CONCLUSIONS/SIGNIFICANCE: Sequential seed mutation of microRNA targets based on
      the SMAP approach allows for rapid structural analysis of several target sites
      within a given 3' UTR. The combination of both methods (SMAP and SLURP) enables
      targeted analysis of microRNA binding sites in hitherto unknown mRNA 3' UTRs
      within a few days.

PMID- 24282595
TI  - Monocytes loaded with indocyanine green as active homing contrast agents permit
      optical differentiation of infectious and non-infectious inflammation.
AB  - Distinguishing cutaneous infection from sterile inflammation is a diagnostic
      challenge and currently relies upon subjective interpretation of clinical
      parameters, microbiological data, and nonspecific imaging. Assessing
      characteristic variations in leukocytic infiltration may provide more specific
      information. In this study, we demonstrate that homing of systemically
      administered monocytes tagged using indocyanine green (ICG), an FDA-approved near
      infrared dye, may be assessed non-invasively using clinically-applicable laser
      angiography systems to investigate cutaneous inflammatory processes. RAW 264.7
      mouse monocytes co-incubated with ICG fluoresce brightly in the near infrared
      range. In vitro, the loaded cells retained the ability to chemotax toward
      monocyte chemotactic protein-1. Following intravascular injection of loaded cells
      into BALB/c mice with induced sterile inflammation (Complete Freund's Adjuvant
      inoculation) or infection (Group A Streptococcus inoculation) of the hind limb,
      non-invasive whole animal imaging revealed local fluorescence at the inoculation
      site. There was significantly higher fluorescence of the inoculation site in the
      infection model than in the inflammation model as early as 2 hours after
      injection (p<0.05). Microscopic examination of bacterial inoculation site tissue
      revealed points of near infrared fluorescence, suggesting the presence of ICG
      loaded cells. Development of a non-invasive technique to rapidly image
      inflammatory states without radiation may lead to new tools to distinguish
      infectious conditions from sterile inflammatory conditions at the bedside.

PMID- 24282596
TI  - The alpha-proteobacteria Wolbachia pipientis protein disulfide machinery has a
      regulatory mechanism absent in gamma-proteobacteria.
AB  - The alpha-proteobacterium Wolbachia pipientis infects more than 65% of insect
      species worldwide and manipulates the host reproductive machinery to enable its
      own survival. It can live in mutualistic relationships with hosts that cause
      human disease, including mosquitoes that carry the Dengue virus. Like many other
      bacteria, Wolbachia contains disulfide bond forming (Dsb) proteins that introduce
      disulfide bonds into secreted effector proteins. The genome of the Wolbachia
      strain wMel encodes two DsbA-like proteins sharing just 21% sequence identity to
      each other, alpha-DsbA1 and alpha-DsbA2, and an integral membrane protein, alpha
      DsbB. alpha-DsbA1 and alpha-DsbA2 both have a Cys-X-X-Cys active site that, by
      analogy with Escherichia coli DsbA, would need to be oxidized to the disulfide
      form to serve as a disulfide bond donor toward substrate proteins. Here we show
      that the integral membrane protein alpha-DsbB oxidizes alpha-DsbA1, but not alpha
      DsbA2. The interaction between alpha-DsbA1 and alpha-DsbB is very specific,
      involving four essential cysteines located in the two periplasmic loops of alpha
      DsbB. In the electron flow cascade, oxidation of alpha-DsbA1 by alpha-DsbB is
      initiated by an oxidizing quinone cofactor that interacts with the cysteine pair
      in the first periplasmic loop. Oxidizing power is transferred to the second
      cysteine pair, which directly interacts with alpha-DsbA1. This reaction is
      inhibited by a non-catalytic disulfide present in alpha-DsbA1, conserved in other
      alpha-proteobacterial DsbAs but not in gamma-proteobacterial DsbAs. This is the
      first characterization of the integral membrane protein alpha-DsbB from Wolbachia
      and reveals that the non-catalytic cysteines of alpha-DsbA1 regulate the redox
      relay system in cooperation with alpha-DsbB. 

PMID- 24282597
TI  - Multi-fiber tractography visualizations for diffusion MRI data.
AB  - In recent years, several new diffusion MRI approaches have been proposed to
      explore microstructural properties of the white matter, such as Q-ball imaging
      and spherical deconvolution-based techniques to estimate the orientation
      distribution function. These methods can describe the estimated diffusion profile
      with a higher accuracy than the more conventional second-rank diffusion tensor
      imaging technique. Despite many important advances, there are still inconsistent
      findings between different models that investigate the "crossing fibers" issue.
      Due to the high information content and the complex nature of the data, it
      becomes virtually impossible to interpret and compare results in a consistent
      manner. In this work, we present novel fiber tractography visualization
      approaches that provide a more complete picture of the microstructural
      architecture of fiber pathways: multi-fiber hyperstreamlines and streamribbons.
      By visualizing, for instance, the estimated fiber orientation distribution along
      the reconstructed tract in a continuous way, information of the local fiber
      architecture is combined with the global anatomical information derived from
      tractography. Facilitating the interpretation of diffusion MRI data, this
      approach can be useful for comparing different diffusion reconstruction
      techniques and may improve our understanding of the intricate white matter
      network. 

PMID- 24282598
TI  - CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in
      neuroinflammation.
AB  - Migration of encephalitogenic CD4(+) T lymphocytes across the blood-brain barrier
      is an essential step in the pathogenesis of multiple sclerosis (MS). We here
      demonstrate that expression of the co-stimulatory receptor NKG2D defines a
      subpopulation of CD4(+) T cells with elevated levels of markers for migration,
      activation, and cytolytic capacity especially when derived from MS patients.
      Furthermore, CD4(+)NKG2D(+) cells produce high levels of proinflammatory IFN
      gamma and IL-17 upon stimulation. NKG2D promotes the capacity of CD4(+)NKG2D(+)
      cells to migrate across endothelial cells in an in vitro model of the blood-brain
      barrier. CD4(+)NKG2D(+) T cells are enriched in the cerebrospinal fluid of MS
      patients, and a significant number of CD4(+) T cells in MS lesions coexpress
      NKG2D. We further elucidated the role of CD4(+)NKG2D(+) T cells in the mouse
      system. NKG2D blockade restricted central nervous system migration of T
      lymphocytes in vivo, leading to a significant decrease in the clinical and
      pathologic severity of experimental autoimmune encephalomyelitis, an animal model
      of MS. Blockade of NKG2D reduced killing of cultivated mouse oligodendrocytes by
      activated CD4(+) T cells. Taken together, we identify CD4(+)NKG2D(+) cells as a
      subpopulation of T helper cells with enhanced migratory, encephalitogenic and
      cytotoxic properties involved in inflammatory CNS lesion development. 

PMID- 24282599
TI  - Prion-seeding activity in cerebrospinal fluid of deer with chronic wasting
      disease.
AB  - Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a
      uniformly fatal family of neurodegenerative diseases in mammals that includes
      chronic wasting disease (CWD) of cervids. The early and ante-mortem
      identification of TSE-infected individuals using conventional western blotting or
      immunohistochemistry (IHC) has proven difficult, as the levels of infectious
      prions in readily obtainable samples, including blood and bodily fluids, are
      typically beyond the limits of detection. The development of amplification-based
      seeding assays has been instrumental in the detection of low levels of infectious
      prions in clinical samples. In the present study, we evaluated the cerebrospinal
      fluid (CSF) of CWD-exposed (n=44) and naive (n=4) deer (n=48 total) for CWD
      prions (PrP(d)) using two amplification assays: serial protein misfolding cyclic
      amplification with polytetrafluoroethylene beads (sPMCAb) and real-time quaking
      induced conversion (RT-QuIC) employing a truncated Syrian hamster recombinant
      protein substrate. Samples were evaluated blindly in parallel with appropriate
      positive and negative controls. Results from amplification assays were compared
      to one another and to obex immunohistochemistry, and were correlated to available
      clinical histories including CWD inoculum source (e.g. saliva, blood), genotype,
      survival period, and duration of clinical signs. We found that both sPMCAb and RT
      QuIC were capable of amplifying CWD prions from cervid CSF, and results
      correlated well with one another. Prion seeding activity in either assay was
      observed in approximately 50% of deer with PrP(d) detected by IHC in the obex
      region of the brain. Important predictors of amplification included duration of
      clinical signs and time of first tonsil biopsy positive results, and ultimately
      the levels of PrP(d) identified in the obex by IHC. Based on our findings, we
      expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for
      the detection of prions in CSF. 

PMID- 24282600
TI  - DB-02, a C-6-cyclohexylmethyl substituted pyrimidinone HIV-1 reverse
      transcriptase inhibitor with nanomolar activity, displays an improved sensitivity
      against K103N or Y181C than S-DABOs.
AB  - 6-(cyclohexylmethyl)-5-ethyl-2-((2-oxo-2-phenylethyl)thio)pyrimidin-4(3H)-one (DB
      02) is a member of the newly reported synthetic anti-HIV-1 compounds dihydro
      aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines, S-DACOs. In vitro anti-HIV-1
      activity and resistance profile studies have suggested that DB-02 has very low
      cytotoxicity (CC50>1mM) to cell lines and peripheral blood mononuclear cells
      (PBMCs). It displays potent anti-HIV-1 activity against laboratory adapted
      strains and primary isolated strains including different subtypes and tropism
      strains (EC50s range from 2.40 to 41.8 nM). Studies on site-directed mutagenesis,
      genotypic resistance profiles revealed that V106A was the major resistance
      contributor for the compound. Molecular docking analysis showed that DB-02
      located in the hydrophobic pocket with interactions of Lys101, Val106, Leu234,
      His235. DB-02 also showed non-antagonistic effects to four approved
      antiretroviral drugs. All studies indicated that DB-02 would be a potential NNRTI
      with low cytotoxicity and improved activity. 

PMID- 24282601
TI  - The origin of the RB1 imprint.
AB  - The human RB1 gene is imprinted due to a differentially methylated CpG island in
      intron 2. This CpG island is part of PPP1R26P1, a truncated retrocopy of PPP1R26,
      and serves as a promoter for an alternative RB1 transcript. We show here by in
      silico analyses that the parental PPP1R26 gene is present in the analysed members
      of Haplorrhini, which comprise Catarrhini (Old World Monkeys, Small apes, Great
      Apes and Human), Platyrrhini (New World Monkeys) and tarsier, and Strepsirrhini
      (galago). Interestingly, we detected the retrocopy, PPP1R26P1, in all
      Anthropoidea (Catarrhini and Platyrrhini) that we studied but not in tarsier or
      galago. Additional retrocopies are present in human and chimpanzee on chromosome
      22, but their distinct composition indicates that they are the result of
      independent retrotransposition events. Chimpanzee and marmoset have further
      retrocopies on chromosome 8 and chromosome 4, respectively. To examine the origin
      of the RB1 imprint, we compared the methylation patterns of the parental PPP1R26
      gene and its retrocopies in different primates (human, chimpanzee, orangutan,
      rhesus macaque, marmoset and galago). Methylation analysis by deep bisulfite
      sequencing showed that PPP1R26 is methylated whereas the retrocopy in RB1 intron
      2 is differentially methylated in all primates studied. All other retrocopies are
      fully methylated, except for the additional retrocopy on marmoset chromosome 4,
      which is also differentially methylated. Using an informative SNP for the
      methylation analysis in marmoset, we could show that the differential methylation
      pattern of the retrocopy on chromosome 4 is allele-specific. We conclude that the
      epigenetic fate of a PPP1R26 retrocopy after integration depends on the DNA
      sequence and selective forces at the integration site. 

PMID- 24282602
TI  - Degeneration of retinal on bipolar cells induced by serum including autoantibody
      against TRPM1 in mouse model of paraneoplastic retinopathy.
AB  - The paraneoplastic retinopathies (PRs) are a group of eye diseases characterized
      by a sudden and progressive dysfunction of the retina caused by an antibody
      against a protein in a neoplasm. Evidence has been obtained that the transient
      receptor potential melastatin 1 (TRPM1) protein was one of the antigens for the
      autoantibody against the ON bipolar cells in PR patients. However, it has not
      been determined how the autoantibody causes the dysfunction of the ON bipolar
      cells. We hypothesized that the antibody against TRPM1 in the serum of patients
      with PR causes a degeneration of retinal ON bipolar cells. To test this
      hypothesis, we injected the serum from the PR patient, previously shown to
      contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and
      examined the effects on the retina. We found that the electroretinograms (ERGs)
      of the mice were altered acutely after the injection, and the shape of the ERGs
      resembled that of the patient with PR. Immunohistochemical analysis of the eyes
      injected with the serum showed immunoreactivity against bipolar cells only in
      wild-type animals and not in TRPM1 knockout mice,consistent with the serum
      containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar
      cells were apoptotic by 5 hours after the injection in wild type mice, but no
      bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner
      nuclear layer was thinner and the amplitudes of the ERGs were still reduced.
      These results indicate that the serum of a patient with PR contained an antibody
      against TRPM1 caused an acute death of retinal ON bipolar cells of mice. 

PMID- 24282603
TI  - Structural insights into the mechanism for recognizing substrate of the
      cytochrome P450 enzyme TxtE.
AB  - Thaxtomins, a family of phytotoxins produced by Streptomyces spp., can cause
      dramatic plant cell hypertrophy and seedling stunting. Thaxtomin A is the
      dominant form from Streptomyces scabies and has demonstrated herbicidal action.
      TxtE, a cytochrome P450 enzyme from Streptomyces scabies 87.22, catalyzes direct
      nitration of the indolyl moiety of L-tryptophan to L-4-nitrotryptophan using
      nitric oxide, dioxygen and NADPH. The crystal structure of TxtE was determined at
      2.1 A resolution and described in this work. A clearly defined substrate access
      channel is observed and can be classified as channel 2a, which is common in
      bacteria cytochrome P450 enzymes. A continuous hydrogen bond chain from the
      active site to the external solvent is observed. Compared with other cytochrome
      P450 enzymes, TxtE shows a unique proton transfer pathway which crosses the helix
      I distortion. Polar contacts of Arg59, Tyr89, Asn293, Thr296, and Glu394 with L
      tryptophan are seen using molecular docking analysis, which are potentially
      important for substrate recognition and binding. After mutating Arg59, Asn293,
      Thr296 or Glu394 to leucine, the substrate binding ability of TxtE was lost or
      decreased significantly. Based on the docking and mutation results, a possible
      mechanism for substrate recognition and binding is proposed. 

PMID- 24282604
TI  - Visual search as a tool for a quick and reliable assessment of cognitive
      functions in patients with multiple sclerosis.
AB  - BACKGROUND: Despite the high frequency of cognitive impairment in multiple
      sclerosis, its assessment has not gained entrance into clinical routine yet, due
      to lack of time-saving and suitable tests for patients with multiple sclerosis.
      OBJECTIVE: The aim of the study was to compare the paradigm of visual search with
      neuropsychological standard tests, in order to identify the test that
      discriminates best between patients with multiple sclerosis and healthy
      individuals concerning cognitive functions, without being susceptible to practice
      effects. METHODS: Patients with relapsing remitting multiple sclerosis (n = 38)
      and age-and gender-matched healthy individuals (n = 40) were tested with common
      neuropsychological tests and a computer-based visual search task, whereby a
      target stimulus has to be detected amongst distracting stimuli on a touch screen.
      Twenty-eight of the healthy individuals were re-tested in order to determine
      potential practice effects. RESULTS: Mean reaction time reflecting visual
      attention and movement time indicating motor execution in the visual search task
      discriminated best between healthy individuals and patients with multiple
      sclerosis, without practice effects. CONCLUSIONS: Visual search is a promising
      instrument for the assessment of cognitive functions and potentially cognitive
      changes in patients with multiple sclerosis thanks to its good discriminatory
      power and insusceptibility to practice effects.

PMID- 24282605
TI  - Population genetic structure of Streptococcus pneumoniae in Kilifi, Kenya, prior
      to the introduction of pneumococcal conjugate vaccine.
AB  - BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced
      in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal
      population structure, thus the aim was to genotype pneumococci collected in
      Kilifi before PCV10. METHODS AND FINDINGS: Using multilocus sequence typing
      (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the
      largest collection genotyped from a single resource-poor country and reported to
      date. Serotype 1 was the most common serotype causing invasive disease and was
      rarely detected in carriage; all serotype 1 isolates were members of clonal
      complex (CC) 217. There were temporal fluctuations in the major circulating
      sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co
      circulated annually, the two major serotype 5 STs mainly circulated
      independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and
      19A and each shared <= 2 MLST alleles with STs that circulate widely elsewhere.
      Major CCs associated with non-PCV10 serotypes were predominantly represented by
      carriage isolates, although serotype 19A and 12F CCs were largely invasive and a
      serotype 10A CC was equally represented by invasive and carriage isolates.
      CONCLUSIONS: Understanding the pre-PCV10 population genetic structure in Kilifi
      will allow for the detection of changes in prevalence of the circulating
      genotypes and evidence for capsular switching post-vaccine implementation.

PMID- 24282606
TI  - The autophagy-related marker LC3 can predict prognosis in human hepatocellular
      carcinoma.
AB  - BACKGROUND: Defects of autophagy and endoplasmic reticulum (ER) stress are
      related to many diseases and tumors. However, only a few studies have examined
      hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this
      study, we investigated the expression and extent of autophagy and ER stress
      related markers in HCC and their influence on clinical characteristics and
      prognosis for each protein. METHODOLOGY: The expression of autophagy-related
      markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was
      analyzed by immunohistochemistry on tissues from completely resected specimens of
      190 HCC patients. Their influence on clinicopathologic features and prognosis
      were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations
      of each protein were determined by Spearman's correlation analysis. PRINCIPAL
      FINDINGS: LC3 expression was not correlated with TNM, BCLC stage, or Edmonson
      Steiner grading, whereas it was correlated with longer overall survival (OS) (p =
      0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068)
      although it did not show statistical significance. Multivariate analysis
      indicated that LC3 expression was a significantly independent prognostic factor
      of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI,
      0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045)
      and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer
      survival, but not in the early stages. A positive correlation was not observed
      between the expression of autophagy-related markers and ER stress-related
      markers. CONCLUSION: Our results suggest that the expression and extent of LC3
      might be a strong prognostic factor of HCC, especially in patients with surgical
      resection.

PMID- 24282607
TI  - Changes in physical activity over time in young children: a longitudinal study
      using accelerometers.
AB  - Previous research has suggested that marked declines in physical activity occur
      during the preschool years, and across the transition into school. However,
      longitudinal studies using objective measures of activity have been limited by
      sample size and length of follow-up. The aims of this study were to determine how
      overall activity and time in different intensities of activity change in children
      followed from 3 to 7 years. Children (n = 242) wore Actical accelerometers at 3,
      4, 5, 5.5, 6.5 and 7 years of age during all waking and sleeping hours for a
      minimum of 5 days. Time in sedentary (S), light (L), moderate (M), and vigorous
      (V) physical activity was determined using available cut points. Data were
      analyzed using a mixed model and expressed as counts per minute (cpm, overall
      activity) and the ratio of active time to sedentary time (LMV:S), adjusted for
      multiple confounders including sex, age, time worn, and weather. At 5 years,
      physical activity had declined substantially to around half that observed at 3
      years. Although starting school was associated with a further short-term (6
      month) decline in activity (cpm) in both boys (difference; 95% CI: -98; -149, 
      46) and girls (-124; -174, -74, both P<0.001), this proved to be relatively
      transient; activity levels were similar at 6-7 years as they were just prior to
      starting school. Boys were more physically active than girls as indicated by an
      overall 12% (95% CI: 2, 22%) higher ratio of active to sedentary time (P =
      0.014), but the pattern of this difference did not change from 3 to 7 years. Time
      worn and weather variables were significant predictors of activity. In
      conclusion, both boys and girls show a marked decline in activity from 3 to 4
      years of age, a decrease that is essentially maintained through to 7 years of
      age. Factors driving this marked decrease need to be determined to enable the
      development of targeted interventions. 

PMID- 24282608
TI  - Timing of surgical intervention with cochlear implant in patients with large
      vestibular aqueduct syndrome.
AB  - OBJECTIVES: (1) To report the speech perception and intelligibility results of
      Mandarin-speaking patients with large vestibular aqueduct syndrome (LVAS) after
      cochlear implantation (CI); (2) to compare their performance with a group of CI
      users without LVAS; (3) to understand the effects of age at implantation and
      duration of implant use on the CI outcomes. The obtained data may be used to
      guide decisions about CI candidacy and surgical timing. METHODS: Forty-two
      patients with LVAS participating in this study were divided into two groups: the
      early group received CI before 5 years of age and the late group after 5. Open
      set speech perception tests (on Mandarin tones, words and sentences) were
      administered one year after implantation and at the most recent follow-up visit.
      Categories of auditory perception (CAP) and Speech Intelligibility Rating (SIR)
      scale scores were also obtained. RESULTS: The patients with LVAS with more than 5
      years of implant use (18 cases) achieved a mean score higher than 80% on the most
      recent speech perception tests and reached the highest level on the CAP/SIR
      scales. The early group developed speech perception and intelligibility steadily
      over time, while the late group had a rapid improvement during the first year
      after implantation. The two groups, regardless of their age at implantation,
      reached a similar performance level at the most recent follow-up visit.
      CONCLUSION: High levels of speech performance are reached after 5 years of
      implant use in patients with LVAS. These patients do not necessarily need to wait
      until their hearing thresholds are higher than 90 dB HL or PB word score lower
      than 40% to receive CI. They can do it "earlier" when their speech perception
      and/or speech intelligibility do not reach the performance level suggested in
      this study.

PMID- 24282609
TI  - Effect of B-vitamin supplementation on stroke: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: B vitamins have been extensively used to reduce homocysteine levels;
      however, it remains uncertain whether B vitamins are associated with a reduced
      risk of stroke. Our aim was to evaluate the effects of B vitamins on stroke.
      METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched PubMed, EmBase,
      and the Cochrane Central Register of Controlled Trials to identify studies for
      our analysis. Relative risk (RR) was used to measure the effect of B-vitamin
      supplementation on the risk of stroke. The analysis was further stratified based
      on factors that could affect the treatment effects. Of the 13,124 identified
      articles, we included 18 trials reporting data on 57,143 individuals and 2,555
      stroke events. B-vitamin supplementation was not associated with a significant
      reduction in the risk of stroke (RR, 0.91, 95%CI: 0.82-1.01, P = 0.075; RD, 
      0.003, 95%CI: -0.007-0.001, P = 0.134). Subgroup analyses suggested that B
      vitamin supplementation might reduce the risk of stroke if included trials had a
      man/woman ratio of more than 2 or subjects received dose of folic acid less than
      1 mg. Furthermore, in a cumulative meta-analysis for stroke, the originally
      proposed nonsignificant B-vitamin effect was refuted by the evidence accumulated
      up to 2006. There is a small effect with borderline statistical significance
      based on data gathered since 2007. CONCLUSIONS/SIGNIFICANCE: Our study indicates
      that B-vitamin supplementation is not associated with a lower risk of stroke
      based on relative and absolute measures of association. Subgroup analyses
      suggested that B-vitamin supplementation can effectively reduce the risk of
      stroke if included trials had a man/woman ratio of more than 2 or subjects
      received dose of folic acid less than 1 mg.

PMID- 24282610
TI  - Gain of function notch phenotypes associated with ectopic expression of the Su(H)
      C-terminal domain illustrate separability of Notch and hairless-mediated
      activities.
AB  - The Notch signaling pathway is instrumental for cell fate decisions. Signals from
      the Notch receptor are transduced by CSL-type DNA-binding proteins. In
      Drosophila, this protein is named Suppressor of Hairless [Su(H)]. Together with
      the intracellular domain of the activated Notch receptor ICN, Su(H) assembles a
      transcriptional activator complex on Notch target genes. Hairless acts as the
      major antagonist of the Notch signaling pathway in Drosophila by means of the
      formation of a repressor complex together with Su(H) and several co-repressors.
      Su(H) is characterized by three domains, the N-terminal domain NTD, the beta
      trefoil domain BTD and the C-terminal domain CTD. NTD and BTD bind to the DNA,
      whereas BTD and CTD bind to ICN. Hairless binds to the CTD, however, to sites
      different from ICN. In this work, we have addressed the question of competition
      and availability of Su(H) for ICN and Hairless binding in vivo. To this end, we
      overexpressed the CTD during fly development. We observed a strong activation of
      Notch signaling processes in various tissues, which may be explained by an
      interference of CTD with Hairless corepressor activity. Accordingly, a combined
      overexpression of CTD together with Hairless ameliorated the effects, unlike
      Su(H) which strongly enhances repression when overexpressed concomitantly with
      Hairless. Interestingly, in the combined overexpression CTD accumulated in the
      nucleus together with Hairless, whereas it is predominantly cytoplasmic on its
      own. 

PMID- 24282612
TI  - Resveratrol enhances airway surface liquid depth in sinonasal epithelium by
      increasing cystic fibrosis transmembrane conductance regulator open probability.
AB  - BACKGROUND: Chronic rhinosinusitis engenders enormous morbidity in the general
      population, and is often refractory to medical intervention. Compounds that
      augment mucociliary clearance in airway epithelia represent a novel treatment
      strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory
      pathway in the nasal airways is governed by the cystic fibrosis transmembrane
      conductance regulator (CFTR). The objectives of the present study were to test
      resveratrol, a strong potentiator of CFTR channel open probability, in
      preparation for a clinical trial of mucociliary activators in human sinus
      disease. METHODS: Primary sinonasal epithelial cells, immortalized
      bronchoepithelial cells (wild type and F508del CFTR), and HEK293 cells expressing
      exogenous human CFTR were investigated by Ussing chamber as well as patch clamp
      technique under non-phosphorylating conditions. Effects on airway surface liquid
      depth were measured using confocal laser scanning microscopy. Impact on CFTR gene
      expression was measured by quantitative reverse transcriptase polymerase chain
      reaction. RESULTS: Resveratrol is a robust CFTR channel potentiator in numerous
      mammalian species. The compound also activated temperature corrected F508del CFTR
      and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo
      to an extent comparable to the recently approved CFTR potentiator, ivacaftor.
      Using inside out patches from apical membranes of murine cells, resveratrol
      stimulated an ~8 picosiemens chloride channel consistent with CFTR. This
      observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of
      sinonasal epithelium resulted in a significant increase in airway surface liquid
      depth (in um: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05). There was no increase
      CFTR mRNA. CONCLUSION: Resveratrol is a potent chloride secretagogue from the
      mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by
      increasing CFTR channel open probability. The foundation for a clinical trial
      utilizing resveratrol as a therapeutic intervention to increase mucociliary
      transport and airway surface liquid hydration in sinus disease is strongly
      supported by these findings.

PMID- 24282611
TI  - Insulin/IGF-I signaling pathways enhances tumor cell invasion through bisecting
      GlcNAc N-glycans modulation. an interplay with E-cadherin.
AB  - Changes in glycosylation are considered a hallmark of cancer, and one of the key
      targets of glycosylation modifications is E-cadherin. We and others have
      previously demonstrated that E-cadherin has a role in the regulation of bisecting
      GlcNAc N-glycans expression, remaining to be determined the E-cadherin-dependent
      signaling pathway involved in this N-glycans expression regulation. In this
      study, we analysed the impact of E-cadherin expression in the activation profile
      of receptor tyrosine kinases such as insulin receptor (IR) and IGF-I receptor
      (IGF-IR). We demonstrated that exogenous E-cadherin expression inhibits IR, IGF
      IR and ERK 1/2 phosphorylation. Stimulation with insulin and IGF-I in MDA-MD-435
      cancer cells overexpressing E-cadherin induces a decrease of bisecting GlcNAc N
      glycans that was accompanied with alterations on E-cadherin cellular
      localization. Concomitantly, IR/IGF-IR signaling activation induced a mesenchymal
      like phenotype of cancer cells together with an increased tumor cell invasion
      capability. Altogether, these results demonstrate an interplay between E-cadherin
      and IR/IGF-IR signaling as major networking players in the regulation of
      bisecting N-glycans expression, with important effects in the modulation of
      epithelial characteristics and tumor cell invasion. Here we provide new insights
      into the role that Insulin/IGF-I signaling play during cancer progression through
      glycosylation modifications. 

PMID- 24282613
TI  - Insulin therapy and risk of prostate cancer: a systematic review and meta
      analysis of observational studies.
AB  - BACKGROUND: Previous observational studies have shown that insulin therapy may
      modify the risk of prostate cancer (PCa). However, these studies yielded
      controversial results. Thus, we performed this meta-analysis to determine whether
      insulin use was associated with PCa risk in patients with diabetes mellitus (DM).
      METHOD: A literature search was carried out in PubMed, EMBASE, and Cochrane
      Library Central database between January 1966 and January 2013. Fixed-effect and
      random-effect models were used to estimate pooled relative risks (RR) and
      corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity
      analyses were also performed. RESULT: A total of 11 (10 cohorts, and one case
      control) studies published between 2007 and 2013 were included in the meta
      analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There
      were five studies investigating the influence of insulin and other glucose
      lowering agents on the risk of PCa , and six studies investigating the influence
      of glargine and non-glargine insulin. Insulin use was not associated with PCa
      risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72
      1.09). Use of insulin glargine did not contribute to susceptibility to PCa as
      compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84).
      Sensitivity analysis confirmed the stability of present results, since no
      individual study affected the pooled result significantly. CONCLUSIONS: Our
      results suggest that, there may be no significant association between insulin use
      and risk of PCa as compared with other glucose-lowering agents in patients with
      DM, and there was no substantial evidence for increase risk of PCa among insulin
      glargine users as compared to non-glargine insulin users. Further studies are
      warranted to validate these conclusions.

PMID- 24282614
TI  - The diagnostic value of CSF alpha-synuclein in the differential diagnosis of
      dementia with Lewy bodies vs. normal subjects and patients with Alzheimer's
      disease.
AB  - The detection of alpha-synuclein (alpha-syn) in the cerebrospinal fluid (CSF) of
      patients with synucleinopathy has yielded promising but inconclusive results. The
      aim of the present study was to determine the diagnostic value of alpha-syn as a
      biological marker for Dementia with Lewy bodies (DLB) vs. normal subjects and
      patients with Alzheimer's disease (AD), after strict control of several
      recognized confounders. Sixteen patients with DLB, 18 patients with AD and 22 age
      and sex-matched normal controls (CTRL) were recruited. The levels of total alpha
      syn in CSF were measured using a novel enzyme-linked immunosorbent assay. There
      was a significant increase of CSF alpha-syn levels in DLB patients as compared to
      the CTRL and AD groups (P = 0.049 and 0.01 respectively). ROC analysis revealed
      that increased alpha-syn was 81.8% specific for the discrimination of DLB vs.
      CTRL and 90% vs. AD. However, sensitivity was lower (56.2 % and 50%
      respectively). These findings provide evidence for a possible diagnostic role of
      alpha-syn as a surrogate biomarker for DLB.

PMID- 24282615
TI  - Variation in specificity of HIV rapid diagnostic tests over place and time: an
      analysis of discordancy data using a Bayesian approach.
AB  - BACKGROUND: Recent trends to earlier access to anti-retroviral treatment
      underline the importance of accurate HIV diagnosis. The WHO HIV testing strategy
      recommends the use of two or three rapid diagnostic tests (RDTs) combined in an
      algorithm and assume a population is serologically stable over time. Yet RDTs are
      prone to cross reactivity which can lead to false positive or discordant results.
      This paper uses discordancy data from Medecins Sans Frontieres (MSF) programmes
      to test the hypothesis that the specificity of RDTs change over place and time.
      METHODS: Data was drawn from all MSF test centres in 2007-8 using a parallel
      testing algorithm. A Bayesian approach was used to derive estimates of disease
      prevalence, and of test sensitivity and specificity using the software WinBUGS. A
      comparison of models with different levels of complexity was performed to assess
      the evidence for changes in test characteristics by location and over time.
      RESULTS: 106, 035 individuals were included from 51 centres in 10 countries using
      7 different RDTs. Discordancy patterns were found to vary by location and time.
      Model fit statistics confirmed this, with improved fit to the data when test
      specificity and sensitivity were allowed to vary by centre and over time. Two
      examples show evidence of variation in specificity between different testing
      locations within a single country. Finally, within a single test centre,
      variation in specificity was seen over time with one test becoming more specific
      and the other less specific. CONCLUSION: This analysis demonstrates the variable
      specificity of multiple HIV RDTs over geographic location and time. This
      variability suggests that cross reactivity is occurring and indicates a higher
      than previously appreciated risk of false positive HIV results using the current
      WHO testing guidelines. Given the significant consequences of false HIV
      diagnosis, we suggest that current testing and evaluation strategies be reviewed.

PMID- 24282616
TI  - Identification of candidate serum proteins for classifying well-differentiated
      small intestinal neuroendocrine tumors.
AB  - BACKGROUND: Patients with well-differentiated small intestine neuroendocrine
      tumors (WD-SI-NETs) are most often diagnosed at a metastatic stage of disease,
      which reduces possibilities for a curative treatment. Thus new approaches for
      earlier detection and improved monitoring of the disease are required. MATERIALS
      AND METHODS: Suspension bead arrays targeting 124 unique proteins with antibodies
      from the Human Protein Atlas were used to profile biotinylated serum samples.
      Discoveries from a cohort of 77 individuals were followed up in a cohort of 132
      individuals both including healthy controls as well as patients with untreated
      primary WD-SI-NETs, lymph node metastases and liver metastases. RESULTS: A set of
      20 antibodies suggested promising proteins for further verification based on
      technically verified statistical significance. Proceeding, we assessed the
      classification performance in an independent cohort of patient serum, achieving,
      classification accuracy of up to 85% with different subsets of antibodies in
      respective pairwise group comparisons. The protein profiles of nine targets,
      namely IGFBP2, IGF1, SHKBP1, ETS1, IL1alpha, STX2, MAML3, EGR3 and XIAP were
      verified as significant contributors to tumor classification. CONCLUSIONS: We
      propose new potential protein biomarker candidates for classifying WD-SI-NETs at
      different stage of disease. Further evaluation of these proteins in larger sample
      sets and with alternative approaches is needed in order to further improve our
      understanding of their functional relation to WD-SI-NETs and their eventual use
      in diagnostics.

PMID- 24282617
TI  - Higher nucleoporin-Importinbeta affinity at the nuclear basket increases
      nucleocytoplasmic import.
AB  - Several in vitro studies have shown the presence of an affinity gradient in
      nuclear pore complex proteins for the import receptor Importinbeta, at least
      partially contributing to nucleocytoplasmic transport, while others have
      historically argued against the presence of such a gradient. Nonetheless, the
      existence of an affinity gradient has remained an uncharacterized contributing
      factor. To shed light on the affinity gradient theory and better characterize how
      the existence of such an affinity gradient between the nuclear pore and the
      import receptor may influence the nucleocytoplasmic traffic, we have developed a
      general-purpose agent based modeling (ABM) framework that features a new method
      for relating rate constants to molecular binding and unbinding probabilities, and
      used our ABM approach to quantify the effects of a wide range of forward and
      reverse nucleoporin-Importinbeta affinity gradients. Our results indicate that
      transport through the nuclear pore complex is maximized with an effective
      macroscopic affinity gradient of 2000 uM, 200 uM and 10 uM in the cytoplasmic,
      central channel and nuclear basket respectively. The transport rate at this
      gradient is approximately 10% higher than the transport rate for a comparable
      pore lacking any affinity gradient, which has a peak transport rate when all
      nucleoporins have an affinity of 200 uM for Importinbeta. Furthermore, this
      optimal ratio of affinity gradients is representative of the ratio of affinities
      reported for the yeast nuclear pore complex--suggesting that the affinity
      gradient seen in vitro is highly optimized.

PMID- 24282618
TI  - Lulu regulates Shroom-induced apical constriction during neural tube closure.
AB  - Apical constriction is an essential cell behavior during neural tube closure, but
      its underlying mechanisms are not fully understood. Lulu, or EPB4.1l5, is a FERM
      domain protein that has been implicated in apical constriction and actomyosin
      contractility in mouse embryos and cultured cells. Interference with the function
      of Lulu in Xenopus embryos by a specific antisense morpholino oligonucleotide or
      a carboxy-terminal fragment of Lulu impaired apical constriction during neural
      plate hinge formation. This effect was likely due to lack of actomyosin
      contractility in superficial neuroectodermal cells. By contrast, overexpression
      of Lulu RNA in embryonic ectoderm cells triggered ectopic apico-basal elongation
      and apical constriction, accompanied by the apical recruitment of F-actin.
      Depletion of endogenous Lulu disrupted the localization and activity of Shroom3,
      a PDZ-containing actin-binding protein that has also been implicated in apical
      constriction. Furthermore, Lulu and Shroom3 RNAs cooperated in triggering ectopic
      apical constriction in embryonic ectoderm. Our findings reveal that Lulu is
      essential for Shroom3-dependent apical constriction during vertebrate neural tube
      closure. 

PMID- 24282619
TI  - Determining the metabolic footprints of hydrocarbon degradation using
      multivariate analysis.
AB  - The functional dynamics of microbial communities are largely responsible for the
      clean-up of hydrocarbons in the environment. However, knowledge of the
      distinguishing functional genes, known as the metabolic footprint, present in
      hydrocarbon-impacted sites is still scarcely understood. Here, we conducted
      several multivariate analyses to characterise the metabolic footprints present in
      a variety of hydrocarbon-impacted and non-impacted sediments. Non-metric multi
      dimensional scaling (NMDS) and canonical analysis of principal coordinates (CAP)
      showed a clear distinction between the two groups. A high relative abundance of
      genes associated with cofactors, virulence, phages and fatty acids were present
      in the non-impacted sediments, accounting for 45.7% of the overall dissimilarity.
      In the hydrocarbon-impacted sites, a high relative abundance of genes associated
      with iron acquisition and metabolism, dormancy and sporulation, motility,
      metabolism of aromatic compounds and cell signalling were observed, accounting
      for 22.3% of the overall dissimilarity. These results suggest a major shift in
      functionality has occurred with pathways essential to the degradation of
      hydrocarbons becoming overrepresented at the expense of other, less essential
      metabolisms.

PMID- 24282620
TI  - Endosomes derived from clathrin-independent endocytosis serve as precursors for
      endothelial lumen formation.
AB  - Clathrin-independent endocytosis (CIE) is a form of bulk plasma membrane (PM)
      endocytosis that allows cells to sample and evaluate PM composition. Once in
      endosomes, the internalized proteins and lipids can be recycled back to the PM or
      delivered to lysosomes for degradation. Endosomes arising from CIE contain lipid
      and signaling molecules suggesting that they might be involved in important
      biological processes. During vasculogenesis, new blood vessels are formed from
      precursor cells in a process involving internalization and accumulation of
      endocytic vesicles. Here, we found that CIE has a role in endothelial lumen
      formation. Specifically, we found that human vascular endothelial cells (HUVECs)
      utilize CIE for internalization of distinct cargo molecules and that in three
      dimensional cultures CIE membranes are delivered to the newly formed lumen. 

PMID- 24282621
TI  - Knockdown of selenocysteine-specific elongation factor in Amblyomma maculatum
      alters the pathogen burden of Rickettsia parkeri with epigenetic control by the
      Sin3 histone deacetylase corepressor complex.
AB  - Selenocysteine is the 21st naturally-occurring amino acid. Selenoproteins have
      diverse functions and many remain uncharacterized, but they are typically
      associated with antioxidant activity. The incorporation of selenocysteine into
      the nascent polypeptide chain recodes the TGA stop codon and this process depends
      upon a number of essential factors including the selenocysteine elongation factor
      (SEF). The transcriptional expression of SEF did not change significantly in tick
      midguts throughout the blood meal, but decreased in salivary glands to 20% at the
      end of the fast feeding phase. Since selenoprotein translation requires this
      specialized elongation factor, we targeted this gene for knockdown by RNAi to
      gain a global view of the role selenoproteins play in tick physiology. We found
      no significant differences in tick engorgement and embryogenesis but detected no
      antioxidant capacity in tick saliva. The transcriptional profile of
      selenoproteins in R. parkeri-infected Amblyomma maculatum revealed declined
      activity of selenoprotein M and catalase and increased activity of selenoprotein
      O, selenoprotein S, and selenoprotein T. Furthermore, the pathogen burden was
      significantly altered in SEF-knockdowns. We then determined the global impact of
      SEF-knockdown by RNA-seq, and mapped huge shifts in secretory gene expression
      that could be the result of downregulation of the Sin3 histone deacetylase
      corepressor complex. 

PMID- 24282622
TI  - Short sleep duration is associated with risk of future diabetes but not
      cardiovascular disease: a prospective study and meta-analysis.
AB  - Epidemiologic studies have observed association between short sleep duration and
      both cardiovascular disease (CVD) and type 2 diabetes, although these results may
      reflect confounding by pre-existing illness. This study aimed to determine
      whether short sleep duration predicts future CVD or type 2 diabetes after
      accounting for baseline health. Baseline data for 241,949 adults were collected
      through the 45 and Up Study, an Australian prospective cohort study, with health
      outcomes identified via electronic database linkage. Cox proportional hazards
      models were used to estimate hazard ratios (HR) and 95% confidence intervals.
      Compared to 7h sleep, <6h sleep was associated with incident CVD in participants
      reporting ill-health at baseline (HR=1.38 [95% CI: 1.12-1.70]), but not after
      excluding those with baseline illness and adjusting for baseline health status
      (1.03 [0.88-1.21]). In contrast, the risk of incident type 2 diabetes was
      significantly increased in those with <6h versus 7h sleep, even after excluding
      those with baseline illness and adjusting for baseline health (HR=1.29 [1.08
      1.53], P=0.004). This suggests the association is valid and does not simply
      reflect confounding or reverse causation. Meta-analysis of ten prospective
      studies including 447,124 participants also confirmed an association between
      short sleep and incident diabetes (1.33 [1.20-1.48]). Obtaining less than 6 hours
      of sleep each night (compared to 7 hours) may increase type 2 diabetes risk by
      approximately 30%.

PMID- 24282623
TI  - Impacts of the "transport subsidy initiative on poor TB patients" in Rural China:
      a patient-cohort based longitudinal study in rural China.
AB  - OBJECTIVE: To describe the financial burden on TB patients for transportation
      during treatment, and to evaluate the impacts of the "transportation subsidy
      initiative on poor TB patients" in rural China for improving poor patients'
      access to TB treatment. METHODS: A Case-cohort of 429 TB patients was
      investigated through questionnaire interviews in four counties of two provinces
      in China. Information on the financial burden for transportation during TB
      diagnosis and treatment was collected. Qualitative in-depth interviews with 26 TB
      patients were carried out to understand their perceptions of transportation
      subsidy initiative. RESULTS: The mean transportation cost of TB medical care was
      97 CNY (70 CNY in median), varying from 0 to 700 CNY. About 51% of the patients
      spent more than 10 CNY per round trip to the TB dispensary. Of the 429 TB
      patients investigated, 139 had received transportation subsidies after getting TB
      diagnosis; 15/139 (10.9%) showed dissatisfaction, mainly because the subsidy
      amount being insufficient. The income of patients receiving transportation
      subsidies was significantly lower than those not receiving the subsidies
      (p<0.05). The impression that an appropriate transportation subsidy enables
      patients to complete the required visits during their TB treatment was obtained
      after observation of over 80% of the patients. CONCLUSION: The transportation
      subsidy plays an important role in reducing financial burden on poor TB patients
      for the completion of treatment. However, the coverage was limited and the amount
      of subsidy was not enough under the present policy. Considering the poverty of
      rural TB patients, a universal coverage and a rational amount of transportation
      subsidy should be proposed.

PMID- 24282624
TI  - The impact of motor axon misdirection and attrition on behavioral deficit
      following experimental nerve injuries.
AB  - Peripheral nerve transection and neuroma-in-continuity injuries are associated
      with permanent functional deficits, often despite successful end-organ
      reinnervation. Axonal misdirection with non-specific reinnervation, frustrated
      regeneration and axonal attrition are believed to be among the anatomical
      substrates that underlie the poor functional recovery associated with these
      devastating injuries. Yet, functional deficits associated with axonal
      misdirection in experimental neuroma-in-continuity injuries have not yet been
      studied. We hypothesized that experimental neuroma-in-continuity injuries would
      result in motor axon misdirection and attrition with proportional persistent
      functional deficits. The femoral nerve misdirection model was exploited to assess
      major motor pathway misdirection and axonal attrition over a spectrum of
      experimental nerve injuries, with neuroma-in-continuity injuries simulated by the
      combination of compression and traction forces in 42 male rats. Sciatic nerve
      injuries were employed in an additional 42 rats, to evaluate the contribution of
      axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks.
      Retrograde motor neuron labeling techniques were utilized to determine the degree
      of axonal misdirection and attrition. Characteristic histological neuroma-in
      continuity features were demonstrated in the neuroma-in-continuity groups and
      poor functional recovery was seen despite successful nerve regeneration and
      muscle reinnervation. Good positive and negative correlations were observed
      respectively between axonal misdirection (p<.0001, r(2)=.67), motor neuron counts
      (attrition) (p<.0001, r(2)=.69) and final functional deficits. We demonstrate
      prominent motor axon misdirection and attrition in neuroma-in-continuity and
      transection injuries of mixed motor nerves that contribute to the long-term
      functional deficits. Although widely accepted in theory, to our knowledge, this
      is the first experimental evidence to convincingly demonstrate these correlations
      with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes
      the need to focus on strategies that promote both robust and accurate nerve
      regeneration to optimize functional recovery. It also demonstrates that
      clinically relevant neuroma-in-continuity injuries can now also be subjected to
      experimental investigation. 

PMID- 24282627
TI  - Clusters in irregular areas and lattices.
AB  - Geographic areas of different sizes and shapes of polygons that represent counts
      or rate data are often encountered in social, economic, health, and other
      information. Often political or census boundaries are used to define these areas
      because the information is available only for those geographies. Therefore, these
      types of boundaries are frequently used to define neighborhoods in spatial
      analyses using geographic information systems and related approaches such as
      multilevel models. When point data can be geocoded, it is possible to examine the
      impact of polygon shape on spatial statistical properties, such as clustering. We
      utilized point data (alcohol outlets) to examine the issue of polygon shape and
      size on visualization and statistical properties. The point data were allocated
      to regular lattices (hexagons and squares) and census areas for zip-code
      tabulation areas and tracts. The number of units in the lattices was set to be
      similar to the number of tract and zip-code areas. A spatial clustering statistic
      and visualization were used to assess the impact of polygon shape for zip- and
      tract-sized units. Results showed substantial similarities and notable
      differences across shape and size. The specific circumstances of a spatial
      analysis that aggregates points to polygons will determine the size and shape of
      the areal units to be used. The irregular polygons of census units may reflect
      underlying characteristics that could be missed by large regular lattices. Future
      research to examine the potential for using a combination of irregular polygons
      and regular lattices would be useful.

PMID- 24282625
TI  - Phenotypic switching induced by damaged matrix is associated with DNA
      methyltransferase 3A (DNMT3A) activity and nuclear localization in smooth muscle
      cells (SMC).
AB  - Extracellular matrix changes are often crucial inciting events for
      fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are
      critical factors underlying differentiated phenotypes. We examined the dependency
      of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases.
      The cooperativity of matrix with growth factors, cell density and hypoxia was
      also examined. Primary rat visceral SMC of early passage (0-2) were plated on
      native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3%
      O2 (balanced 5% CO2 and 95% N2) over 48 hours. Inhibitors were applied 2-3 hours
      after cells were plated on matrix, or immediately before hypoxia. Cells were
      fixed and stained for DNMT3A and smooth muscle actin (SMA) or smooth muscle
      myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite
      converted DNA from smooth muscle cells on damaged matrix vs native collagen.
      Matrix exquisitely regulates DNMT3A localization and expression, and influences
      differentiation in SMCs exposed to denatured matrix +/- hypoxia. Analysis of DNA
      methylation signatures showed that Matrix caused significant DNA methylation
      alterations in a discrete number of CpG sites proximal to genes related to SMC
      differentiation. Matrix has a profound effect on the regulation of SMC phenotype,
      which is associated with altered expression, localization of DNMTs and discrete
      changes DNA methylation. 

PMID- 24282626
TI  - Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in
      Nepal: an open-label, randomized, controlled trial.
AB  - BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials
      for the treatment of enteric fever, but no direct comparison between two
      fluoroquinolones has been performed in a large randomised trial. An open-label
      randomized trial was conducted to investigate whether gatifloxacin is more
      effective than ofloxacin in the treatment of uncomplicated enteric fever caused
      by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.
      METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with
      uncomplicated enteric fever were enrolled in the study to receive gatifloxacin
      (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses
      for 7 days. Patients were followed for six months. The primary outcome was
      treatment failure in patients infected with nalidixic acid resistant isolates.
      627 patients with a median age of 17 (IQR 9-23) years were randomised. Of the 218
      patients with culture confirmed enteric fever, 170 patients were infected with
      nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients
      had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard
      ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median
      time to fever clearance was 4.70 days (IQR 2.98-5.90) in the ofloxacin group
      versus 3.31 days (IQR 2.29-4.75) in the gatifloxacin group (HR = 1.59, 95% CI
      1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and
      all randomized patients were comparable. CONCLUSION: Gatifloxacin was not
      superior to ofloxacin in preventing failure, but use of gatifloxacin did result
      in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION:
      ISRCTN 63006567 (www.controlled-trials.com).

PMID- 24282628
TI  - Dietary anthocyanins as nutritional therapy for nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), defined by excessive lipid accumulation
      in the liver, is the hepatic manifestation of insulin resistance and the
      metabolic syndrome. Due to the epidemics of obesity, NAFLD is rapidly becoming
      the leading cause of altered liver enzymes in Western countries. NAFLD
      encompasses a wide spectrum of liver disease ranging from simple uncomplicated
      steatosis, to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Diet may
      affect the development of NAFLD either by increasing risk or by providing
      protective factors. Therefore, it is important to investigate the role of foods
      and/or food bioactives on the metabolic processes involved in steatohepatitis for
      preventive strategies. It has been reported that anthocyanins (ACNs) decrease
      hepatic lipid accumulation and may counteract oxidative stress and hepatic
      inflammation, but their impact on NAFLD has yet to be fully determined. ACNs are
      water-soluble bioactive compounds of the polyphenol class present in many
      vegetable products. Here, we summarize the evidence evaluating the mechanisms of
      action of ACNs on hepatic lipid metabolism in different experimental setting: in
      vitro, in vivo, and in human trials. Finally, a working model depicting the
      possible mechanisms underpinning the beneficial effects of ACNs in NAFLD is
      proposed, based on the available literature. 

PMID- 24282629
TI  - Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative
      glomerulonephritis successfully treated with bortezomib.
AB  - Extracapillary-proliferative glomerulonephritis is a rare complication of
      multiple myeloma. Partial remission of kidney involvement with cyclophosphamide
      therapy has previously been described. We report the case of a 60-year-old male
      patient diagnosed with rapidly progressive glomerulonephritis associated with IgG
      kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune
      extracapillary-proliferative glomerulonephritis without cryoglobulinaemia.
      Treatment with the proteasome inhibitor bortezomib induced rapid clinical and
      histological remission of his kidney disease. The patient's renal function
      remained stable on bortezomib maintenance therapy. Our findings suggest that
      bortezomib is a promising therapeutic approach to ameliorate severe kidney damage
      in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary
      proliferative glomerulonephritis.

PMID- 24282630
TI  - An extensive replication study on three new susceptibility Loci of primary angle
      closure glaucoma in han chinese: jiangsu eye study.
AB  - Genome-wide association study (GWAS) analysis identified three new susceptibility
      loci for PACG. In this study, we aimed to investigate whether these three loci in
      PLEKHA7, COL11A1, and PCMTD1-ST18 are associated with PAC and ocular biometric
      characteristics, such as axial length (AL), anterior chamber depth (ACD), and
      diopter of spherical power (DS). The study was a part of the Jiangsu Eye Study.
      The samples were collected from 232 PAC subjects and 306 controls from a
      population-based prevalence survey conducted in Funing County of Jiangsu, China.
      The single nucleotide polymorphisms (SNPs) of rs11024102 in PLEKHA7, rs3753841 in
      COL11A1, and rs1015213 in PCMTD1-ST18 were genotyped by TaqMan-MGB probe using
      the RT-PCR system. None of the three polymorphisms showed differences in the
      distribution of genotypes and allele frequencies between the PAC group and the
      control group. No significant association was determined between the 3 SNPs and
      AL, ACD, or DS of PAC subjects. We concluded that even though PLEKHA7 rs11024102,
      COL11A1 rs3753841, and PCMTD1-ST18 rs1015213 are associated with PACG, those
      sequence variations are not associated with PAC in a Han Chinese population. Our
      results also did not support a significant role for these three SNPs in ocular
      biometry such as AL, ACD, and DS. 

PMID- 24282631
TI  - Long-lasting effects of oxy- and sulfoanalogues of L-arginine on enzyme actions.
AB  - Arginine residues are very important for the structure of proteins and their
      action. Arginine is essential for many natural processes because it has unique
      ionizable group under physiological conditions. Numerous mimetics of arginine
      were synthesized and their biological effects were evaluated, but the mechanisms
      of actions are still unknown. The aim of this study is to see if oxy- and
      sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase
      (HArgS)-an enzyme responsible for coupling of L-arginine with its cognate tRNA in
      a two-step catalytic reaction. We make use of modeling and docking studies of
      adenylate kinase (ADK) to reveal the effects produced by the incorporation of the
      arginine mimetics on the structure of ADK and its action. Three analogues of
      arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg),
      can be recognized as substrates of HArgS when incorporated in different peptide
      and protein sequences instead of L-arginine. Mutation in the enzyme active center
      by arginine mimetics leads to conformational changes, which produce a decrease
      the rate of the enzyme catalyzed reaction and even a loss of enzymatic action.
      All these observations could explain the long-lasting nature of the effects of
      the arginine analogues. 

PMID- 24282632
TI  - Impact of a traditional dietary supplement with coconut milk and soya milk on the
      lipid profile in normal free living subjects.
AB  - Background. The effects of coconut fat and soya fat on serum lipids are
      controversial. This study was designed to investigate the lipid effects of
      coconut milk and soya milk supplementation on the lipid profile of free living
      healthy subjects. Methods. Sixty (60) healthy volunteers aged 18-57 years were
      given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by
      a 2-week washout period, subsequent to which they received isoenergetic soya milk
      porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels
      decreased with CMP and reached statistical significance in the total study
      population and in the >130 baseline LDL group. The HDL (high density lipoprotein)
      levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We
      conclude that coconut fat in the form of CM does not cause a detrimental effect
      on the lipid profile in the general population and in fact is beneficial due to
      the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose
      baseline LDL levels are elevated. 

PMID- 24282633
TI  - Differentiated thyroid cancer: indications and extent of central neck dissection-
      our experience.
AB  - The aim of this retrospective study was to determine the rate of metastases in
      the central neck compartment and examine the morbidity and rate of recurrence in
      patients with differentiated thyroid cancer treated with or without a central
      neck dissection. Two hundred and fifteen patients undergoing total thyroidectomy
      with preoperative diagnosis of differentiated thyroid cancer, in the absence of
      suspicious nodes, were divided in two groups: those who underwent a thyroidectomy
      only (group A; n = 169) and those who also received a central neck dissection
      (group B; n = 46). Five cases (2.32%) of nodal recurrence were observed: 3 in
      group A and 2 in group B. Tumor histology was associated with a risk of
      recurrence: Hurthle cell-variant and tall cell-variant carcinomas were associated
      with a high risk of recurrence. Multifocality and extrathyroidal invasion also
      presented a higher risk, while smaller tumors were at lower risk. The results of
      this study suggest that prophylactic central neck dissection should be reserved
      for high-risk patients only. A wider use of immunocytochemical and genetic
      markers to improve preoperative diagnosis and the development of methods for the
      intraoperative identification of metastatic lymph nodes will be useful in the
      future for the improved selection of patients for central neck dissections. 

PMID- 24282634
TI  - Health literacy and global cognitive function predict e-mail but not internet use
      in heart failure patients.
AB  - Background. The internet offers a potential for improving patient knowledge, and
      e-mail may be used in patient communication with providers. However, barriers to
      internet and e-mail use, such as low health literacy and cognitive impairment,
      may prevent patients from using technological resources. Purpose. We investigated
      whether health literacy, heart failure knowledge, and cognitive function were
      related to internet and e-mail use in older adults with heart failure (HF).
      Methods. Older adults (N = 119) with heart failure (69.84 +/- 9.09 years)
      completed measures of health literacy, heart failure knowledge, cognitive
      functioning, and internet use in a cross-sectional study. Results. Internet and e
      mail use were reported in 78.2% and 71.4% of this sample of patients with HF,
      respectively. Controlling for age and education, logistic regression analyses
      indicated that higher health literacy predicted e-mail (P < .05) but not internet
      use. Global cognitive function predicted e-mail (P < .05) but not internet use.
      Only 45% used the Internet to obtain information on HF and internet use was not
      associated with greater HF knowledge. Conclusions. The majority of HF patients
      use the internet and e-mail, but poor health literacy and cognitive impairment
      may prevent some patients from accessing these resources. Future studies that
      examine specific internet and email interventions to increase HF knowledge are
      needed. 

PMID- 24282635
TI  - Associations between Psychosocial and Physiological Factors and Diabetes Health
      Indicators in Asian and Pacific Islander Adults with Type 2 Diabetes.
AB  - The associations between psychosocial and physiological factors and diabetes'
      health indicators have not been widely investigated among Asians and Pacific
      Islanders. We hypothesize that health behaviour and depression are directly or
      indirectly associated with diabetes' health indicators such as BMI, glycemic
      control, general health, and diabetes quality of life. Our hypothesis was tested
      through a structural equation modelling (SEM) approach. Questionnaires that
      assessed health behaviour, depression, general health, diabetes quality of life,
      and haemoglobin A1c (HbA1c), along with patients' demographic information, were
      obtained from 207 Asian and Pacific Islander adults with type 2 diabetes. IBM
      SPSS Amos 20 was used for the SEM analysis at 5% level of significance, and the
      goodness fit of the SEM model was also evaluated. The final SEM model showed that
      diet and exercise and foot care had positive associations, while depression had a
      negative association with diabetes' health indicators. The results highlighted
      the importance of exercise and depression in diabetes patients' BMI, glycemic
      control, general health, and quality of life, which provide evidence for the need
      to alleviate patients' depression besides education and training in diet and
      exercise in future intervention studies among Asians and Pacific Islanders with
      type 2 diabetes. 

PMID- 24282636
TI  - Drug Resistance Pattern of MTB Isolates from PTB Patients.
AB  - Background. TB is a global pandemic disease. All TB control programs were not
      successful due to the emergence of multidrug resistance in M. tuberculosis
      strains. Objective of the present study was to detect the rate of MDR-MTB in this
      part of India. Methods. One hundred and thirty clinical MTB strains isolated from
      patients on treatment and confirmed as MTB by MPT64 antigen detection were tested
      for drug susceptibility against Streptomycin, INH, Rifampicin, and Ethambutol by
      MBBact automated system. Result. Thirty-two were MDRs (25.61%). 31.2%, 28%,
      17.6%, and 21.6% were resistant to INH, RIF, Ethambutol, and Streptomycin,
      respectively. Resistance to either INH or Rifampicin was 20.8% and 13.88%,
      respectively. Combined INH and Rifampicin resistance was seen in 18.05% isolates.
      Conclusion. Drug resistance rate is high in patients treated previously and who
      have been irregular on treatment. 

PMID- 24282637
TI  - Peritoneal dialysis-moving from current status to the future.

PMID- 24282638
TI  - Decision making processes and outcomes.
AB  - The primary aim of this study was to examine the contributions of individual
      characteristics and strategic processing to the prediction of decision quality.
      Data were provided by 176 adults, ages 18 to 93 years, who completed computerized
      decision-making vignettes and a battery of demographic and cognitive measures. We
      examined the relations among age, domain-specific experience, working memory, and
      three measures of strategic information search to the prediction of solution
      quality using a 4-step hierarchical linear regression analysis. Working memory
      and two measures of strategic processing uniquely contributed to the variance
      explained. Results are discussed in terms of potential advances to both theory
      and intervention efforts. 

PMID- 24282639
TI  - Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear
      Factor-kappaB Signaling Pathway.
AB  - Background. There is an urgent need to develop new treatment strategies and drugs
      for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus
      hippocastanum (the horse chestnut) known in Chinese medicine as a plant with anti
      inflammatory, antiedema, antianalgesic, and antipyretic activities. The main
      active compound of this plant is Escin (C54H84O23). Objective. To evaluate the
      effect of Escin alone and combined with chemotherapy on pancreatic cancer cell
      survival and to unravel mechanism(s) of Escin anticancer activity. Methods. Cell
      survival was measured by XTT colorimetric assay. Synergistic effect of combined
      therapy was determined by CalcuSyn software. Cell cycle and induction of
      apoptosis were evaluated by FACS analysis. Expression of NF- kappa B-related
      proteins (p65, I kappa Balpha, and p-I kappa Balpha) and cyclin D was evaluated
      by western blot analysis. Results. Escin decreased the survival of pancreatic
      cancer cells with IC50 = 10-20 M. Escin combined with gemcitabine showed only
      additive effect, while its combination with cisplatin resulted in a significant
      synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin
      induced apoptosis and decreased NF- kappa B-related proteins and cyclin D
      expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced
      apoptosis, and downregulated NF- kappa B signaling pathway. Moreover, Escin
      sensitized pancreatic cancer cells to chemotherapy. Further translational
      research is required. 

PMID- 24282641
TI  - The impact on emergency department utilization and patient flows after
      integrating with a general practitioner cooperative: an observational study.
AB  - Introduction. A new model, an emergency care access point (ECAP) for after-hours
      emergency care, is emerging in The Netherlands. This study assessed the effect on
      emergency department (ED) utilization and patient flows. Methods. Routinely
      recorded clinical ED patient data, covering a six-year period, was collected.
      Segmented regression analysis was used to analyze after-hours changes over time.
      Results. 59.182 patients attended the ED before the start of the ECAP and 51.513
      patients after, a decrease of 13%. Self-referred ED patients decreased 99.5% (OR
      0.003; 95% CI 0.002-0.004). Referred patients increased by 213.4% and ED hospital
      admissions increased by 20.2%. A planned outpatient follow-up increased by 5.8%
      (OR 1.968 95% CI 1.870-2.071). The latter changed from fewer contacts to more
      contacts (OR 1.015 95% CI 1.013-1.017). Consultations at the regional genereral
      practitioner cooperative (GPC) increased by 26.0% (183.782 versus 232.246).
      Conclusion. ECAP implementation resulted in a decrease in ED utilization, a near
      absence of self-referring patients, and a higher probability of hospital
      admission and clinical follow-up. This suggests either an increase of ED patients
      with a higher acuity or a lower threshold of admitting referred patients compared
      to self-referred patients. Overall, increased collaboration with after-hours
      primary care and emergency care seemed to optimize ED utilization. 

PMID- 24282640
TI  - SEM, TEM, and IHC Analysis of the Sinus Node and Its Implications for the Cardiac
      Conduction System.
AB  - More than 100 years after the discovery of the sinus node (SN) by Keith and
      Flack, the function and structure of the SN have not been completely established
      yet. The anatomic architecture of the SN has often been described as devoid of an
      organized structure; the origin of the sinus impulse is still a matter of debate,
      and a definite description of the long postulated internodal specialized tract
      conducting the impulse from the SN to the atrioventricular node (AVN) is still
      missing. In our previously published study, we proposed a morphologically ordered
      structure for the SN. As a confirmation of what was presented then, we have added
      the results of additional observations regarding the structural particularities
      of the SN. We investigated the morphology of the sinus node in the human hearts
      of healthy individuals using histochemical, immunohistochemical, optical, and
      electron microscopy (SEM, TEM). Our results confirmed that the SN presents a
      previously unseen highly organized architecture. 

PMID- 24282642
TI  - Evaluation of Apical Microleakage in Open Apex Teeth Using MTA Apical Plug in
      Different Sessions.
AB  - Aim. To compare microleakage of apexification using MTA in one or two sessions.
      Materials and Methods. 88 single rooted teeth were prepared and divided into two
      groups then received MTA apical plug. In the first group, the teeth were immersed
      in normal saline for 24 hours and then backfilled with guttapercha and AH26
      sealer. In the second group, the teeth were obturated immediately after receiving
      apical plug. Four positive and four negative controls were selected. All
      specimens were placed in 1% methylene blue and decalcified in 5% nitric acid and
      finally were placed in methyl salicylate until getting transparent. All teeth
      were visualized for assessment of dye penetration under stereo dissecting
      microscope. Results. 36 and 35 teeth showed dye leakage in the first and second
      groups. Dye penetration into the entire canal length was confirmed in the
      positive control group, and in the negative control group no dye penetration was
      seen. Mean dye penetration in the first and second group was 5813 and 9152  MU m.
      t-test revealed a significant difference between dye penetrations of two groups
      (P < 0.05). Conclusion. MTA requires adequate time for setting in the presence of
      the moisture, and final obturation should be delayed until final setting of MTA. 

PMID- 24282643
TI  - Solvent-Free Green and Efficient One-Pot Synthesis of Dihydropyrano[3,2
      c]chromene Derivatives.
AB  - A rapid, clean, and highly efficient method for synthesis of dihydropyrano[3,2
      c]chromene derivatives by one-pot, three-component condensation of aromatic
      aldehydes, malononitrile, and 4-hydroxycoumarin using DABCO as catalyst in
      solvent-free neat conditions is described. The present method has the advantages
      of mild reaction conditions, short reaction times, easy isolation of products,
      and excellent yields. 

PMID- 24282644
TI  - Effect of socks on the assessment of vibration sensation.
AB  - Objective. To investigate the difference between the measurement of vibration
      sensation without and with socks. Material and Methods. Fifty healthy volunteers
      (H group) and 19 patients with diabetic polyneuropathy (PNP group) were included.
      The sites of measurement were the great toe (GT) and medial malleolus (MM). A
      standard 128 Hz tuning fork was used in the measurements. Results. Mean duration
      of vibration sensations without and with socks was as follows: in the H group,
      19.4 +/- 4.2 and 19.5 +/- 4.2 s at GT and 15.1 +/- 3.3 and 14.6 +/- 3.3 s at MM;
      in the PNP group, 13.4 +/- 3.8 and 12.7 +/- 4.1 s at GT and 11.9 +/- 3.8 and 11.7
      +/- 3.4 s at MM. No significant difference was found between the measurements
      without and with socks, except those found at the MM in group H (P = 0.02). This
      significant difference was further analyzed in terms of effect size which was
      concluded to be practically insignificant (Cohen's d < 0.2). Shorter mean
      vibration duration was measured at MM as compared to GT that could be explained
      by the damping effect. Conclusions. Wearing socks of moderate thickness does not
      have any important effect on the duration of vibration sensation. This might be
      considered as a reflection of the remarkable properties of vibration sensation. 

PMID- 24282645
TI  - Development of a closed chest model of chronic myocardial infarction in Swine:
      magnetic resonance imaging and pathological evaluation.
AB  - Our aim was to develop an easy-to-induce, reproducible, and low mortality
      clinically relevant closed-chest model of chronic myocardial infarction in swine
      using intracoronary ethanol and characterize its evolution using MRI and
      pathology. We injected 3-4 mL of 100% ethanol into the mid-LAD of anesthetized
      swine. Heart function and infarct size were assessed serially using MRI. Pigs
      were euthanized on days 7, 30, and 90 (n = 5 at each timepoint). Postoperative
      MRI revealed compromised contractility and decreased ejection fraction, from
      53.8% +/- 6.32% to 43.79% +/- 7.72% (P = 0.001). These values remained lower than
      baseline thorough the followup (46.54% +/- 11.12%, 44.48% +/- 7.77%, and 40.48%
      +/- 6.40%, resp., P < 0.05). Progressive remodeling was seen in all animals.
      Infarcted myocardium decreased on the first 30 days (from 18.09% +/- 7.26% to
      9.9% +/- 5.68%) and then stabilized (10.2% +/- 4.21%). Pathology revealed
      increasing collagen content and fibrous organization over time, with a rim of
      preserved endocardial cells. In conclusion, intracoronary ethanol administration
      in swine consistently results in infarction. The sustained compromise in heart
      function and myocardial thinning over time indicate that the model may be useful
      for the preclinical evaluation of and training in therapeutic approaches to heart
      failure. 

PMID- 24282646
TI  - Sound sensitivity of the saccule for low frequencies in healthy adults.
AB  - Approximately 80 years ago John Tait speculated about a possible auditory role
      for the otolith organs in humans those days, there was no direct evidence for
      that idea. This time is for us to review and research. Then, the objective of our
      study was to investigate saccular hearing in healthy adults. We selected twenty
      healthy controls and twenty-four dizzy cases. Assessment comprised of audiologic
      evaluations, cervical vestibular evoked myogenic potentials (cVEMPs), and
      recognition of spoken phonemes in white noise (Rsp in wn). In the case group (a
      total of 48 ears), the cVEMPs abnormalities were all unilateral (24 affected ears
      and 24 contralateral unaffected ears). Affected ears with decreased vestibular
      excitability as detected by abnormal cVEMPs had decreased Rsp in wn (mean = 60.78
      +/- 8.33), whereas both unaffected (mean = 96.24 +/- 2.4) and control ears (mean
      = 96.24 +/- 2.4) presented normal results. The correlation between RSP in wn and
      p13 latencies was significant (P < 0.05, r = -0.551). The peak-to-peak amplitudes
      showed significant correlation to RSP in wn (P < 0.05, r = 0.307). The
      correlation between RSP in wn and the latencies of n23 was significant (P < 0.05,
      r = -0.493). We concluded in presence of severe competing noise, saccule has a
      facilitating role for cochlea and can improve to detection of loud low
      frequencies. 

PMID- 24282647
TI  - Benign paroxysmal positional vertigo in irradiated nasopharyngeal carcinoma
      survivors.
AB  - Purpose. It has been assumed that postirradiated nasopharyngeal carcinoma (NPC)
      patients are prone to benign paroxysmal positional vertigo (BPPV). The purpose of
      this study was to better understand this clinical entity. Materials and Methods.
      From September 2003 to June 2011, we conducted a retrospective study of 11
      irradiated NPC patients with BPPV in our institute. During the same period, 11
      irradiated NPC patients without BPPV were randomly selected and enrolled as the
      control group. All medical records of these patients were evaluated. Results. The
      risk of BPPV rises significantly when the patient undergoes radiotherapy (RT)
      twice and the threshold radiation dose is >120 Gy (P = 0.027). The occurrence of
      postirradiated BPPV was significantly related to incidences of otitis media and
      sensorineural hearing loss (SNHL) (P = 0.011 and 0.009, resp.). All the patients
      responded well to repositioning maneuvers. Conclusion. A second course of RT,
      postirradiated otitis media, or SNHL is associated with the potential risk of
      radiation-induced BPPV. Repositioning maneuvers were safe and effective for
      relief of this disease. 

PMID- 24282648
TI  - Management of root fracture: a novel, noninvasive treatment approach.
AB  - Traumatic injuries to teeth account for approximately 25% of dental conditions
      where a patient seeks dentist for emergency treatment. Radicular fractures are
      one such entity which is very challenging to address due to various complications
      like periodontal communication, increased mobility, and continued pulpal
      infection leading to necrosis. Radicular fractures in the middle third have long
      been considered teeth of salvage due to their unfavourable fracture pattern.
      During the recent years introduction of biomimetic materials has opened the
      horizon for saving these teeth. In the present case report a novel approach to
      the management of radicular fractures in the middle third has been presented. 

PMID- 24282649
TI  - Successful management of metastatic eccrine porocarcinoma.
AB  - Eccrine porocarcinoma (EPC) is a rare tumor. It develops from the intraepidermal
      ductal portion of the eccrine sweat gland. Metastatic disease is rare. We report
      a new case of metastatic eccrine porocarcinoma with a successful management and a
      good response to docetaxel. A 54-year-old man was admitted with a mass in the
      breast. Biopsy specimen found carcinomatous tumor proliferation with large
      anastomosing ducts. Cellular atypia were noted, with eosinophilic cytoplasm and
      round to oval nuclei. The tumor showed positive immunoreactivity for ACE and
      negative to anti-PS-100. Resection was performed. One year later, he presented
      with local and metastatic recurrences. The patient had received 3 cycles of
      cisplatin and 5-fluorouracil; he progressed with increase in mass size and number
      of lung lesions. He has been undergoing three cycles of docetaxel with complete
      response in the lung and regression of the breast mass. The mass was excised.
      Porocarcinoma is a very rare entity and poorly understood. In the metastatic
      phase, it has modest or no sensitivity to anticancer treatment. Docetaxel should
      be considered in the metastatic eccrine porocarcinoma. 

PMID- 24282650
TI  - Cupping Therapy May be Harmful for Eczema: A PubMed Search.
AB  - Eczema is a common childhood atopic condition and treatment is with emollients,
      topical corticosteroids, and avoidance of possible triggers. S. aureus
      colonization is a common complication. As there is no immediate cure, many
      parents seek alternative therapies that claim unproven therapeutic efficacy. We
      report a girl with long history of treatment noncompliance. After practicing a
      long period of dietary avoidance and supplementation, the grandparents took her
      to an alternative medicine practitioner. Following cupping therapy and
      acupuncture, the child developed blistering and oozing over her back the next
      day, which rapidly evolved to two large irregular-edge deep ulcers. She was
      treated with intravenous antibiotics and received multidisciplinary supportive
      intervention. Using search words of  "cupping," "eczema," and "atopic
      dermatitis," only two reports were found on PubMed. Therapeutic efficacy was
      claimed but not scientifically documented in these reports. Childhood eczema is
      an eminently treatable atopic disease. Extreme alternative therapy seems not to
      be efficacious and may even be associated with serious undesirable sequelae.
      Physicians should be aware of various alternative treatment modalities and be
      prepared to offer evidence-based advice to the patients with eczema and their
      families. 

PMID- 24282651
TI  - Microemulsion liquid chromatographic method for simultaneous determination of
      simvastatin and ezetimibe in their combined dosage forms.
AB  - A rapid HPLC procedure using a microemulsion as an eluent was developed and
      validated for analytical quality control of antihyperlipidemic mixture containing
      simvastatin (SIM) and ezetimibe (EZT) in their pharmaceutical preparations. The
      separation was performed on a column packed with cyano bonded stationary phase
      adopting UV detection at 238 nm using a flow rate of 1 mL/min. The optimized
      microemulsion mobile phase consisted of 0.2 M sodium dodecyl sulphate, 1%
      octanol, 10% n-propanol, and 0.3% triethylamine in 0.02 M phosphoric acid at pH
      5.0. The developed method was validated in terms of specificity, linearity, lower
      limit of quantification (LOQ), lower limit of detection (LOD), precision, and
      accuracy. The proposed method is rapid (8.5 min), reproducible (RSD < 2.0%) and
      achieves satisfactory resolution between SIM and EZT (resolution factor = 2.57).
      The mean recoveries of the analytes in pharmaceutical preparations were in
      agreement with those obtained from a reference method, as revealed by statistical
      analysis of the obtained results using Student's t-test and the variance ratio F
      test. 

PMID- 24282652
TI  - Combination of ERG9 Repression and Enzyme Fusion Technology for Improved
      Production of Amorphadiene in Saccharomyces cerevisiae.
AB  - The yeast strain (Saccharomyces cerevisiae) MTCC 3157 was selected for
      combinatorial biosynthesis of plant sesquiterpene amorpha-4,11-diene. Our main
      objective was to overproduce amorpha 4-11-diene, which is a key precursor
      molecule of artemisinin (antimalarial drug) produced naturally in plant Artemisia
      annua through mevalonate pathway. Farnesyl diphosphate (FPP) is a common
      intermediate metabolite of a variety of compounds in the mevalonate pathway of
      yeast and leads to the production of ergosterols, dolichol and ubiquinone, and so
      forth. In our studies, FPP converted to amorphadiene (AD) by expressing
      heterologous amorphadiene synthase (ADS) in yeast. First, ERG9 (squalane
      synthase) promoter of yeast was replaced with repressible methionine (MET3)
      promoter by using bipartite gene fusion method. Further to overcome the loss of
      the intermediate FPP through competitive pathways in yeast, fusion protein
      technology was adopted and farnesyldiphosphate synthase (FPPS) of yeast has been
      coupled with amorphadiene synthase (ADS) of plant origin (Artemisia annua L.)
      where amorphadiene production was improved by 2-fold (11.2 mg/L) and 4-fold
      (25.02 mg/L) in yeast strains YCF-002 and YCF-005 compared with control strain
      YCF-AD (5.5 mg/L), respectively. 

PMID- 24282654
TI  - About transitions.

PMID- 24282653
TI  - Recognition of FT-IR Data Cuscutae Semen, Japanese Dodder, and Sinapis Semen
      Using Discrete Wavelet Transformation and RBF Networks.
AB  - Horizontal attenuation total reflection Fourier transformation infrared
      spectroscopy (HATR-FT-IR) studies on cuscutae semen and its confusable varieties
      Japanese dodder and sinapis semen combined with discrete wavelet transformation
      (DWT) and radial basis function (RBF) neural networks have been conducted in
      order to classify them. DWT is used to decompose the FT-IRs of cuscutae semen,
      Japanese dodder, and sinapis semen. Two main scales are selected as the feature
      extracting space in the DWT domain. According to the distribution of cuscutae
      semen, Japanese dodder, and sinapis semen's FT-IRs, three feature regions are
      determined at detail 3, and two feature regions are determined at detail 4 by
      selecting two scales in the DWT domain. Thus five feature parameters form the
      feature vector. The feature vector is input to the RBF neural networks to train
      so as to accurately classify the cuscutae semen, Japanese dodder, and sinapis
      semen. 120 sets of FT-IR data are used to train and test the proposed method,
      where 60 sets of data are used to train samples, and another 60 sets of FT-IR
      data are used to test samples. Experimental results show that the accurate
      recognition rate of cuscutae semen, Japanese dodder, and sinapis semen is average
      of 100.00%, 98.33%, and 100.00%, respectively, following the proposed method. 

PMID- 24282655
TI  - Dermatopathology: an abridged compendium of words. A discussion of them and
      opinions about them. Part 2.

PMID- 24282656
TI  - The relevance of recognizing clinical and morphologic features of pityriasis
      lichenoides: clinicopathological study of 29 cases.
AB  - BACKGROUND: Pityriasis lichenoides (PL) is a lymphoproliferative disease of
      unknown origin; its diagnosis is based on clinical characteristics and confirmed
      by histology. OBJECTIVES: To describe clinical and histological features of PL in
      29 pediatric patients. MATERIALS AND METHODS: Retrospective descriptive study of
      children (patients less than 15 years old) diagnosed with PL between 1986 and
      2010 at a Reference Service in Pediatric Dermatology from South Brazil. RESULTS:
      Twenty-nine PL cases were found by chart review in 24 years. Mean age of
      diagnosis was 8 years (22 to 178 months) and a mean time of diagnosis was 13.8
      months (1 to 120 months). Twenty cases (69%) were male. Seasonal correlation was
      found with colder months in 62% of cases (p<0.01). Clinical diagnosis was
      pityriasis lichenoides chronica (PLC) in 25 cases, and pityriasis lichenoides et
      varioliformis acuta (PLEVA) in four. Itching was the main reported symptom
      occurring in 13 (45%). Fourteen cases had been histologically evaluated. In six,
      microscopic findings were consistent with PLC, in four consistent with PLEVA, and
      four biopsies exhibited mixed characteristics of both forms. Concordance between
      clinical and histological diagnosis was seen in most cases. CONCLUSION: PL occurs
      in children and young adults, more commonly in males, and during cold months. PLC
      was the more frequent clinicohistologic form, and necrotic lesions characterized
      PLEVA. Associating clinical and histological findings is important for
      differentiating between PLC and PLEVA diagnosis.

PMID- 24282657
TI  - Clinical, dermoscopic and histopathologic findings of retiform
      hemangioendothelioma.
AB  - Retiform hemangioendothelioma (RH) is an uncommon vascular neoplasm of borderline
      malignancy that clinically develops as a solitary, gradually enlarging exophytic
      mass, nodule or plaque, most often on the lower limbs, upper limbs and trunk.
      Clinical recognition of RH is troublesome because of its non-specific appearance,
      with differential diagnosis comprising a variety of benign and malignant tumors
      clinically presenting as reddish nodules. In this article we describe the
      clinical, dermoscopic and histopathologic findings in a case of RH developing on
      the flank of a 26-year-old woman, and discuss the possible role of dermoscopy in
      facilitating the clinical recognition of this rare tumor. 

PMID- 24282658
TI  - A verrucous plaque on the lower leg.

PMID- 24282660
TI  - Inguinal porokeratosis in a Japanese man.
AB  - Inguinal and genital porokeratosis are rare but seem to be more common in Asians.
      We report a case of a 69-year-old Japanese man with multiple lesions of
      porokeratosis in both inguinal regions. The lesions first appeared in the
      inguinal region and subsequently spread to the trunk. The patient reported that
      his father had had similar lesions. Dermoscopy demonstrated central brown
      pigmentation and blue-gray dots surrounded by a single "white track" at the
      periphery. The exterior border of the white track also showed light brown
      pigmentation. Genital or inguinal porokeratosis is uncommon and may be
      misdiagnosed as Bowen's disease, lichen planus or extramammary Paget's disease.
      However, awareness of this entity and the use of dermoscopy are helpful to
      establish a correct diagnosis. 

PMID- 24282659
TI  - Systematic review of diagnostic accuracy of reflectance confocal microscopy for
      melanoma diagnosis in patients with clinically equivocal skin lesions.
AB  - BACKGROUND: Melanoma is a cancer of the skin and is increasing in incidence in
      the UK and Europe. Melanoma is a condition that is often curable if detected at
      an early stage, which makes accurate diagnosis vital. Reflectance confocal
      microscopy (RCM) is a tool used to image the skin. It gives high magnification
      images of the skin, which may provide more accurate diagnosis of lesions that are
      equivocal on clinical examination and dermoscopy. OBJECTIVE: To determine the
      diagnostic accuracy of reflectance confocal microscopy (RCM), for melanoma
      diagnosis, as an add-on test to clinical examination and dermoscopy in the
      diagnosis of equivocal pigmented skin lesions using histopathology as the
      reference standard. METHODS: A search was conducted of MEDLINE, EMBASE and six
      other electronic databases from inception to present. Forward citation searching
      and hand searching of reference lists were also conducted. Diagnostic accuracy
      studies that assess RCM in the diagnosis of melanoma were included in the review.
      Two contributors conducted the search, data extraction and assessment of
      methodological quality using QUADAS-2. Statistical analysis was performed using
      hierarchical bivariate random effects meta-analysis. RESULTS: 951 titles and
      abstracts were screened. Five studies comprising 909 lesions were eligible for
      meta-analysis. Meta-analysis returned a per lesion sensitivity of 93% [95% CI 89
      96] and a specificity of 76% [95% CI 68-83]. CONCLUSIONS: The utility of
      reflectance confocal microscopy (RCM) as an add-on test for the diagnosis of
      melanoma depends on the trade off between over-excising benign lesions and
      misdiagnosing melanoma as benign. This becomes important when considering lesions
      on surgically difficult or cosmetically important areas of the body.

PMID- 24282661
TI  - Prevention of possible cross-infection among patients by dermoscopy: a brief
      review of the literature and our suggestion.

PMID- 24282662
TI  - Self-assembly of a simple low-cost dermoscope for examination of skin lesions.

PMID- 24282663
TI  - The importance of gray color as a dermoscopic clue in facial pigmented lesion
      evaluation: a case report.

PMID- 24282664
TI  - Dermoscopy: What is your diagnosis?

PMID- 24282665
TI  - The halo split skin graft in the management of non-melanoma skin cancer of the
      leg: a retrospective study.
AB  - BACKGROUND: The purpose of this study was to compare the results of the halo
      split skin graft (HSSG) by two primary care skin cancer practitioners at one
      clinic at the Gold Coast, Queensland, Australia, to the results of the only
      previous study while adding to the body of evidence regarding use of the HSSG
      following excision of non-melanoma skin cancer on the leg. METHOD: A
      retrospective review of the notes (Jan 2010-Aug 2012) was performed of all cases
      of nonmelanoma skin cancer (NMSC) excisions in which split skin graft (SSG)
      closure with the HSSG was utilized on the leg. RESULTS: There were a total of 68
      HSSGs included over the 31 months of the study. Average lesion size was 19.4 mm
      (range 9-75 mm) and the average age of patients was 78 years (range 49-95 years)
      with 49% of patients being male. The average healing time was 4 weeks with 35/68
      (51%) healing within 14 to 21 days. The overall infection rate was 8/68 (11.8%),
      which decreased to 4/53 (7.5%) when the ankle grafts were excluded. The graft
      failure rate was 7/68 (10%) with 3/68 (4.4%) having both infection and graft
      failure. LIMITATIONS: This was a retrospective study. CONCLUSION: The HSSG
      confines the surgical wounds to a single site, does not require specialized
      equipment and it is an economical and effective option for managing NMSC on the
      leg in situations where skin graft is indicated.

PMID- 24282666
TI  - Review of practical dermatopathology by ronald p. Rapini.

PMID- 24282667
TI  - A rare case of syphilis associated with renal and hepatic involvement.
AB  - We present an unusual case of syphilis that despite starting treatment with
      penicillin has evolved with renal complications. Due to glomerulonephritis with
      nephrotic syndrome the case required shared care between the renal physician and
      dermatologist. Doctors of different specialties need to keep in mind that early
      syphilis can have visceral involvement and patients might need prompt, specific
      therapeutic intervention. 

PMID- 24282668
TI  - Squamous cell carcinoma of the soft palate associated with autoantibodies to
      desmoglein 1 and 3.

PMID- 24282669
TI  - ezRAD: a simplified method for genomic genotyping in non-model organisms.
AB  - Here, we introduce ezRAD, a novel strategy for restriction site-associated DNA
      (RAD) that requires little technical expertise or investment in laboratory
      equipment, and demonstrate its utility for ten non-model organisms across a wide
      taxonomic range. ezRAD differs from other RAD methods primarily through its use
      of standard Illumina TruSeq library preparation kits, which makes it possible for
      any laboratory to send out to a commercial genomic core facility for library
      preparation and next-generation sequencing with virtually no additional
      investment beyond the cost of the service itself. This simplification opens
      RADseq to any lab with the ability to extract DNA and perform a restriction
      digest. ezRAD also differs from others in its flexibility to use any restriction
      enzyme (or combination of enzymes) that cuts frequently enough to generate
      fragments of the desired size range, without requiring the purchase of separate
      adapters for each enzyme or a sonication step, which can further decrease the
      cost involved in choosing optimal enzymes for particular species and research
      questions. We apply this method across a wide taxonomic diversity of non-model
      organisms to demonstrate the utility and flexibility of our approach. The
      simplicity of ezRAD makes it particularly useful for the discovery of single
      nucleotide polymorphisms and targeted amplicon sequencing in natural populations
      of non-model organisms that have been historically understudied because of lack
      of genomic information. 

PMID- 24282670
TI  - Effects of ocean acidification on the dissolution rates of reef-coral skeletons.
AB  - Ocean acidification threatens the foundation of tropical coral reefs. This study
      investigated three aspects of ocean acidification: (i) the rates at which
      perforate and imperforate coral-colony skeletons passively dissolve when pH is
      7.8, which is predicted to occur globally by 2100, (ii) the rates of passive
      dissolution of corals with respect to coral-colony surface areas, and (iii) the
      comparative rates of a vertical reef-growth model, incorporating passive
      dissolution rates, and predicted sea-level rise. By 2100, when the ocean pH is
      expected to be 7.8, perforate Montipora coral skeletons will lose on average 15
      kg CaCO3 m(-2) y(-1), which is approximately -10.5 mm of vertical reduction of
      reef framework per year. This rate of passive dissolution is higher than the
      average rate of reef growth over the last several millennia and suggests that
      reefs composed of perforate Montipora coral skeletons will have trouble keeping
      up with sea-level rise under ocean acidification. Reefs composed of primarily
      imperforate coral skeletons will not likely dissolve as rapidly, but our model
      shows they will also have trouble keeping up with sea-level rise by 2050. 

PMID- 24282671
TI  - An empirical evaluation of four variants of a universal species-area
      relationship.
AB  - The Maximum Entropy Theory of Ecology (METE) predicts a universal species-area
      relationship (SAR) that can be fully characterized using only the total abundance
      (N) and species richness (S) at a single spatial scale. This theory has shown
      promise for characterizing scale dependence in the SAR. However, there are
      currently four different approaches to applying METE to predict the SAR and it is
      unclear which approach should be used due to a lack of empirical comparison.
      Specifically, METE can be applied recursively or non-recursively and can use
      either a theoretical or observed species-abundance distribution (SAD). We
      compared the four different combinations of approaches using empirical data from
      16 datasets containing over 1000 species and 300,000 individual trees and herbs.
      In general, METE accurately downscaled the SAR (R (2) > 0.94), but the recursive
      approach consistently under-predicted richness. METE's accuracy did not depend
      strongly on using the observed or predicted SAD. This suggests that the best
      approach to scaling diversity using METE is to use a combination of non-recursive
      scaling and the theoretical abundance distribution, which allows predictions to
      be made across a broad range of spatial scales with only knowledge of the species
      richness and total abundance at a single scale. 

PMID- 24282672
TI  - Examination of spotted sand bass (Paralabrax maculatofasciatus) pollutant
      bioaccumulation in San Diego Bay, San Diego, California.
AB  - The spotted sand bass (Paralabrax maculatofasciatus) is an important recreational
      sport and subsistence food fish within San Diego Bay, a large industrialized
      harbor in San Diego, California. Despite this importance, few studies examining
      the species life history relative to pollutant tissue concentrations and the
      consumptive fishery exist. This study utilized data from three independent
      spotted sand bass studies from 1989 to 2002 to investigate PCB, DDT, and mercury
      tissue concentrations relative to spotted sand bass age and growth in San Diego
      Bay, with subsequent comparisons to published pollutant advisory levels and
      fishery regulations for recreational and subsistence consumption of the species.
      Subsequent analysis focused on examining temporal and spatial differences for
      different regions of San Diego Bay. Study results for growth confirmed previous
      work, finding the species to exhibit highly asymptotic growth, making tissue
      pollutant concentrations at initial take size difficult if not impossible to
      predict. This was corroborated by independent tissue concentration results for
      mercury, which found no relationship between fish size and pollutant
      bioaccumulation observed. However, a positive though highly variable relationship
      was observed between fish size and PCB tissue concentration. Despite these
      findings, a significant proportion of fish exhibited pollutant levels above
      recommended state recreational angler consumption advisory levels for PCBs and
      mercury, especially for fish above the minimum take size, making the necessity of
      at-size predictions less critical. Lastly, no difference in tissue concentration
      was found temporally or spatially within San Diego Bay. 

PMID- 24282673
TI  - Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in
      epilepsy-related gene expression.
AB  - To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV),
      have been reported in several animal models of seizure. However, these
      behaviourally observed anticonvulsant effects have not been confirmed at the
      molecular level. To examine changes to epilepsy-related gene expression following
      chemical convulsant treatment and their subsequent control by phytocannabinoid
      administration, we behaviourally evaluated effects of CBDV (400 mg/kg, p.o.) on
      acute, pentylenetetrazole (PTZ: 95 mg/kg, i.p.)-induced seizures, quantified
      expression levels of several epilepsy-related genes (Fos, Casp 3, Ccl3, Ccl4,
      Npy, Arc, Penk, Camk2a, Bdnf and Egr1) by qPCR using hippocampal, neocortical and
      prefrontal cortical tissue samples before examining correlations between
      expression changes and seizure severity. PTZ treatment alone produced generalised
      seizures (median: 5.00) and significantly increased expression of Fos, Egr1, Arc,
      Ccl4 and Bdnf. Consistent with previous findings, CBDV significantly decreased
      PTZ-induced seizure severity (median: 3.25) and increased latency to the first
      sign of seizure. Furthermore, there were correlations between reductions of
      seizure severity and mRNA expression of Fos, Egr1, Arc, Ccl4 and Bdnf in the
      majority of brain regions in the CBDV+PTZ treated group. When CBDV treated
      animals were grouped into CBDV responders (criterion: seizure severity <=3.25)
      and non-responders (criterion: seizure severity >3.25), PTZ-induced increases of
      Fos, Egr1, Arc, Ccl4 and Bdnf expression were suppressed in CBDV responders.
      These results provide the first molecular confirmation of behaviourally observed
      effects of the non-psychoactive, anticonvulsant cannabinoid, CBDV, upon
      chemically-induced seizures and serve to underscore its suitability for clinical
      development. 

PMID- 24282674
TI  - Predominant intragenic methylation is associated with gene expression
      characteristics in a bivalve mollusc.
AB  - Characterization of DNA methylation patterns in the Pacific oyster, Crassostrea
      gigas, indicates that this epigenetic mechanism plays an important functional
      role in gene regulation and may be involved in the regulation of developmental
      processes and environmental responses. However, previous studies have been
      limited to in silico analyses or characterization of DNA methylation at the
      single gene level. Here, we have employed a genome-wide approach to gain insight
      into how DNA methylation supports the regulation of the genome in C. gigas. Using
      a combination of methylation enrichment and high-throughput bisulfite sequencing,
      we have been able to map methylation at over 2.5 million individual CpG loci.
      This is the first high-resolution methylome generated for a molluscan species.
      Results indicate that methylation varies spatially across the genome with a
      majority of the methylated sites mapping to intra genic regions. The bisulfite
      sequencing data was combined with RNA-seq data to examine genome-wide
      relationships between gene body methylation and gene expression, where it was
      shown that methylated genes are associated with high transcript abundance and low
      variation in expression between tissue types. The combined data suggest DNA
      methylation plays a complex role in regulating genome activity in bivalves. 

PMID- 24282675
TI  - The relationship between resilience and personality traits in doctors:
      implications for enhancing well being.
AB  - Objective. The health and well being of medical doctors is vital to their
      longevity and safe practice. The concept of resilience is recognised as a key
      component of well being and is an important factor in medical training to help
      doctors learn to cope with challenge, stress, and adversity. This study examined
      the relationship of resilience to personality traits and resilience in doctors in
      order to identify the key traits that promote or impair resilience. Methods. A
      cross sectional cohort of 479 family practitioners in practice across Australia
      was studied. The Temperament and Character Inventory measured levels of the seven
      basic dimensions of personality and the Resilience Scale provided an overall
      measure of resilience. The associations between resilience and personality were
      examined by Pearson product-moment correlation coefficients, controlling for age
      and gender (alpha = 0.05 with an accompanying 95% confidence level) and multiple
      regression analyses. Results. Strong to medium positive correlations were found
      between Resilience and Self-directedness (r = .614, p < .01), Persistence (r =
      .498, p < .01), and Cooperativeness (r = .363, p < .01) and negative with Harm
      Avoidance (r = .-555, p < .01). Individual differences in personality explained
      39% of the variance in resilience [F(7, 460) = 38.40, p < .001]. The three traits
      which contributed significantly to this variance were Self-directedness (beta =
      .33, p < .001), Persistence (beta = .22, p < .001) and Harm Avoidance (beta =
      .19, p < .001). Conclusion. Resilience was associated with a personality trait
      pattern that is mature, responsible, optimistic, persevering, and cooperative.
      Findings support the inclusion of resilience as a component of optimal
      functioning and well being in doctors. Strategies for enhancing resilience should
      consider the key traits that drive or impair it. 

PMID- 24282676
TI  - Role of the hypoxia response pathway in lens formation during embryonic
      development of Xenopus laevis.
AB  - The RING finger ubiquitin ligase seven in absentia homolog 2 (Siah2) was
      identified in the R7 photoreceptor cells of Drosophila melanogaster, and it
      regulates the stability of prolyl hydroxylase domains (PHDs), with a concomitant
      effect on HIF-1alpha availability in the hypoxia response pathway. We previously
      reported that the hypoxia response pathway contributes to eye development during
      the embryonic development of Xenopus laevis. In this paper, the role of Siah2
      mediated hypoxia response pathway in eye development of X. laevis embryos was
      further characterized. Xenopus Siah2 (xSiah2) mRNA was detected in lens tissue
      and xSiah2 overexpression caused a thickened lens placode, leading to loss of the
      optic lens. In embryos overexpressing xSiah2, lens marker gene transcription was
      reduced, suggesting that xSiah2 contributes to lens formation. xSiah2
      overexpression decreased Xenopus PHD accumulation and increased Xenopus HIF
      1alpha (xHIF-1alpha) accumulation. xHIF-1alpha degeneration with resveratrol
      restored the optical abnormality caused by xSiah2 overexpression, suggesting that
      the xSiah2-mediated hypoxia response pathway contributes to lens formation.
      Moreover, xSiah2 overexpression decreased endothelial-mesenchymal transition
      (EMT)-related Notch signaling-responsive genes transcription during the invasion
      of the lens placode. Our results suggest that the hypoxia response pathway plays
      an important role in the regulation of the EMT via the Notch signaling pathway
      during lens formation. 

PMID- 24282677
TI  - Crystal structures of Phanerochaete chrysosporium pyranose 2-oxidase suggest that
      the N-terminus acts as a propeptide that assists in homotetramer assembly.
AB  - The flavin-dependent homotetrameric enzyme pyranose 2-oxidase (P2O) is found
      mostly, but not exclusively, in lignocellulose-degrading fungi where it catalyzes
      the oxidation of beta-d-glucose to the corresponding 2-keto sugar concomitantly
      with hydrogen peroxide formation during lignin solubilization. Here, we present
      crystal structures of P2O from the efficient lignocellulolytic basidiomycete
      Phanerochaete chrysosporium. Structures were determined of wild-type PcP2O from
      the natural fungal source, and two variants of recombinant full-length PcP2O,
      both in complex with the slow substrate 3-deoxy-3-fluoro-beta-d-glucose. The
      active sites in PcP2O and P2O from Trametes multicolor (TmP2O) are highly
      conserved with identical substrate binding. Our structural analysis suggests that
      the 17  degrees C higher melting temperature of PcP2O compared to TmP2O is due to
      an increased number of intersubunit salt bridges. The structure of recombinant
      PcP2O expressed with its natural N-terminal sequence, including a proposed
      propeptide segment, reveals that the first five residues of the propeptide
      intercalate at the interface between A and B subunits to form stabilizing, mainly
      hydrophobic, interactions. In the structure of mature PcP2O purified from the
      natural source, the propeptide segment in subunit A has been replaced by a nearby
      loop in the B subunit. We propose that the propeptide in subunit A stabilizes the
      A/B interface of essential dimers in the homotetramer and that, upon maturation,
      it is replaced by the loop in the B subunit to form the mature subunit interface.
      This would imply that the propeptide segment of PcP2O acts as an intramolecular
      chaperone for oligomerization at the A/B interface of the essential dimer.

PMID- 24282680
TI  - Cardiovascular Diagnosis and Therapy (CDT): yet another journal?

PMID- 24282681
TI  - A histopathological comparison of different definitions for quantifying in-stent
      neointimal tissue: implications for the validity of intracoronary ultrasound and
      optical coherence tomography measurements.
AB  - PURPOSE: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT)
      define neointima as the tissue encompassed between the stent and the lumen
      boundaries. This approach differs from the gold-standard histopathology, where
      neointima is traditionally calculated as the tissue between the internal elastic
      lamina (IEL) and the lumen. We aimed to investigate whether the neointimal
      assessment using IVUS and OCT-like definitions would correlate with the
      traditional histopathological quantification of neointima. METHODS:
      Histopathological analysis was obtained from a porcine model of 28-day coronary
      in-stent neointimal proliferation (n=13 bare stents). Traditional histopathology
      neointimal area (NIHPATH area) was calculated as the lumen area minus the IEL
      area, while the percent neointimal obstruction was defined as NIHPATH area
      divided by the IEL area. The IVUS/OCT-like neointima area (NIHIVUS/OCT area) was
      defined as the lumen area minus the stent area, while the percent neointimal
      obstruction was defined as NIHIVUS/OCT area divided by the stent area. RESULTS:
      The neointimal area as well as the percent obstruction were significantly
      correlated between histopathology and IVUS/OCT-like definitions (R(2)=0.89 and
      0.95 respectively; P<0.01 for both). The average absolute difference between the
      IVUS/OCT-like and the pathology-like measurements was close to zero, however with
      a relatively wide dispersion (difference for neointimal area: 0.41 mm(2) [95% CI
      1.72 to (-)0.90 mm(2)]; difference for percent neointimal obstruction: 2.5% [95%
      CI 11.5% to (-)6.5%]). CONCLUSIONS: The present findings support the use of stent
      area in replacement to IEL area, as in IVUS & OCT imaging protocols, for the
      calculation of neointimal parameters in experimental model of restenosis.

PMID- 24282678
TI  - Multimodal neuroimaging in presurgical evaluation of drug-resistant epilepsy.
AB  - Intracranial EEG (icEEG) monitoring is critical in epilepsy surgical planning,
      but it has limitations. The advances of neuroimaging have made it possible to
      reveal epileptic abnormalities that could not be identified previously and
      improve the localization of the seizure focus and the vital cortex. A frequently
      asked question in the field is whether non-invasive neuroimaging could replace
      invasive icEEG or reduce the need for icEEG in presurgical evaluation. This
      review considers promising neuroimaging techniques in epilepsy presurgical
      assessment in order to address this question. In addition, due to large
      variations in the accuracies of neuroimaging across epilepsy centers, multicenter
      neuroimaging studies are reviewed, and there is much need for randomized
      controlled trials (RCTs) to better reveal the utility of presurgical
      neuroimaging. The results of multiple studies indicate that non-invasive
      neuroimaging could not replace invasive icEEG in surgical planning especially in
      non-lesional or extratemporal lobe epilepsies, but it could reduce the need for
      icEEG in certain cases. With technical advances, multimodal neuroimaging may play
      a greater role in presurgical evaluation to reduce the costs and risks of
      epilepsy surgery, and provide surgical options for more patients with drug
      resistant epilepsy. 

PMID- 24282679
TI  - Functional characterization of genetic enzyme variations in human lipoxygenases.
AB  - Mammalian lipoxygenases play a role in normal cell development and
      differentiation but they have also been implicated in the pathogenesis of
      cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid
      peroxidizing enzymes they are involved in the regulation of cellular redox
      homeostasis since they produce lipid hydroperoxides, which serve as an efficient
      source for free radicals. There are various epidemiological correlation studies
      relating naturally occurring variations in the six human lipoxygenase genes (SNPs
      or rare mutations) to the frequency for various diseases in these individuals,
      but for most of the described variations no functional data are available.
      Employing a combined bioinformatical and enzymological strategy, which included
      structural modeling and experimental site-directed mutagenesis, we systematically
      explored the structural and functional consequences of non-synonymous genetic
      variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and
      ALOX15B) that have been identified in the human 1000 genome project. Due to a
      lack of a functional expression system we resigned to analyze the functionality
      of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the
      frequent non-synonymous coding SNPs are located at the enzyme surface and hardly
      alter the enzyme functionality. In contrast, genetic variations which affect
      functional important amino acid residues or lead to truncated enzyme variations
      (nonsense mutations) are usually rare with a global allele frequency<0.1%. This
      data suggest that there appears to be an evolutionary pressure on the coding
      regions of the lipoxygenase genes preventing the accumulation of loss-of-function
      variations in the human population. 

PMID- 24282682
TI  - Echocardiographic guidance for diagnostic and therapeutic percutaneous
      procedures.
AB  - Echocardiographic guidance has an important role in percutaneous cardiovascular
      procedures and vascular access. The advantages include real time imaging,
      portability, and availability, which make it an effective imaging modality. This
      article will review the role of echocardiographic guidance for diagnostic and
      therapeutic percutaneous procedures, specifically, transvenous and transarterial
      access, pericardiocentesis, endomyocardial biopsy, transcatheter pulmonary valve
      replacement, pulmonary valve repair, transcatheter aortic valve implantation, and
      percutaneous mitral valve repair. We will address the ways in which
      echocardiographic guidance provides these procedures with detailed information on
      anatomy, adjacent structures, and intraprocedural instrument position, thus
      resulting in improvement in procedural efficacy, safety and patient outcomes. 

PMID- 24282683
TI  - The coronary slow flow phenomenon: characteristics, mechanisms and implications.
AB  - The coronary slow flow phenomenon (CSFP) is an important, angiographic entity
      characterized by delayed progression of the injected contrast medium through the
      coronary tree. It is a frequent finding, typically observed in patients
      presenting with acute coronary syndromes. Although it is well known to
      interventional cardiologists for approximately four decades, the pathogenic
      mechanisms remain unclear. The clinical implications are significant, with over
      80% of patients experiencing recurrent chest pain, resulting in considerable
      impairment in quality of life. This article will address in detail the
      characteristics, possible mechanisms, and clinical implications of this entity to
      provide further insight into its clinical significance and management strategies.

PMID- 24282684
TI  - Computed tomography in the evaluation for transcatheter aortic valve implantation
      (TAVI).
AB  - If left untreated, symptomatic, severe aortic stenosis (AS) is associated with a
      dismal prognosis. Open-heart surgical valve replacement is the treatment of
      choice and is associated with excellent short and long-term outcome. However,
      many older patients with multiple co-morbidities and anticipated increased
      surgical risk are excluded from surgical intervention. For these patients,
      transcatheter aortic valve implantation (TAVI) is emerging as a viable treatment
      alternative. Transcatheter valvular heart procedures are characterized by lack of
      exposure and visualization of the operative field, therefore relying on image
      guidance, both for patient selection and preparation and the implantation
      procedure itself. This article describes the role of multi-detector row computed
      tomography (MDCT) for detailed assessment of the aortic valve, aortic root, and
      iliac arteries in the context of TAVI. 

PMID- 24282685
TI  - QCA, IVUS and OCT in interventional cardiology in 2011.
AB  - Over the past 30 years, quantitative coronary arteriography (QCA) has been used
      extensively as an objective and reproducible tool in clinical research to assess
      changes in vessel dimensions as a result of interventions, but also as a tool to
      provide evidence to the interventionalist prior to and after an intervention and
      at follow-up when necessary. With the increasing complexities of bifurcation
      stenting, corresponding analytical tools for bifurcation analysis have been
      developed with extensive reporting schemes. Although intravascular ultrasound
      (IVUS) has been around for a long time as well, more recent radiofrequency
      analysis provides additional information about the vessel wall composition;
      likewise optical coherence tomography (OCT) provides detailed information about
      the positions of the stent struts and the quality of the stent placement.
      Combining the information from the X-ray lumenogram and the intravascular imaging
      devices is mentally a challenging task for the interventionalist. To support the
      registration of these intravascular images with the X-ray images, 3D QCA has been
      developed and registered with the IVUS or OCT images, so that at every position
      along the vessel of interest the luminal data and the vessel wall data by IVUS or
      the stent strut data by OCT can be combined. From the 3D QCA the selection of the
      optimal angiographic views can also be facilitated. It is the intention of this
      overview paper to provide an extensive description of the techniques that we have
      developed and validated over the past 30 years. 

PMID- 24282687
TI  - Blue berg.

PMID- 24282686
TI  - Contemporary art in medicine: the Cleveland Clinic art collection.
AB  - Fine art is good medicine. It comforts, elevates the spirit, and affirms life and
      hope. Art in the healthcare setting, combined with outstanding care and service,
      creates an environment that encourages healing and supports the work of medical
      professionals. As one of the world's great medical centers, Cleveland Clinic has
      always included the arts in its healing environment. The four founders and
      subsequent leadership encouraged artistic and musical expression by employees.
      Distinguished artworks have long hung on the walls. In 1983, an Aesthetics
      Committee was officially formed at Cleveland Clinic to address issues of art and
      design in Cleveland Clinic facilities. 

PMID- 24282688
TI  - "Quelque part dans le monde" (somewhere in the world).

PMID- 24282689
TI  - Communication of novel concepts.

PMID- 24282690
TI  - Variability in the intima-media thickness measurement as marker for
      cardiovascular risk? Not quite settled yet.

PMID- 24282691
TI  - Grading aortic stenosis severity when the flow modifies the gradientvalve area
      correlation.

PMID- 24282692
TI  - Intima Media Thickness Variability (IMTV) and its association with
      cerebrovascular events: a novel marker of carotid therosclerosis?
AB  - PURPOSE: Increased intima-media thickness (IMT) is an early marker of
      atherosclerotic disease and several prospective studies have demonstrated that
      IMT is a strong predictor of cerebrovascular complications. In this paper we
      propose a novel method to assess IMT, called "intima media thickness variability"
      (IMTV) and evaluate its relationship with the development of cerebrovascular
      events. MATERIAL AND METHODS: The study was approved by the local IRB. Twenty
      consecutive patients underwent ultrasound analysis of the carotid arteries (mean
      age 68 years; age range 59-81 years). The IMT and IMTV of the 40 carotid vessels
      was assessed. Bland-Altman statistics were employed to measure the inter-observer
      variability, and ROC analysis was used to assess the association with
      cerebrovascular events. RESULTS: In all cases the ROC area under the curve was
      higher for IMTV than IMT. There was a statistical significant association between
      IMTV and cerebrovascular events (P=0.018), but no relationship between IMT and
      events. The results for inter-observer variability showed a systematic error
      between 0.04 and 0.08 mm. In the Person Rho correlation analysis in no case a
      statistical association between IMT and symptoms was detected whereas in 2 cases
      (observer 1 and observer 2), a statistically significant association between IMTV
      and symptoms was found. CONCLUSIONS: Data of this preliminary study suggest that
      IMTV may represent a powerful method to assess carotid atherosclerotic disease
      with a significant association to cerebrovascular events.

PMID- 24282693
TI  - Low gradient "severe" aortic stenosis with preserved left ventricular ejection
      fraction.
AB  - In developed nations, aortic stenosis (AS) is the most common valvular heart
      disease presentation, and its prevalence is increasing due to aging populations.
      Accurate diagnosis of the disease process and determination of its severity are
      essential in clinical decision-making. Although current guidelines recommend
      measuring transvalvular gradients, maximal velocity, and aortic valve area in
      determining the disease severity, inconsistent grading of disease severity
      remains a common problem in clinical practice. Recent studies suggest that
      patients with paradoxical low-flow and/or low-gradient, severe AS are at a more
      advanced stage of the disease process and have a poorer prognosis. This mode of
      presentation may lead to an undervaluation of symptoms and inappropriate delay of
      AVR. Therefore, this challenging clinical situation should be carefully assessed
      in particular in symptomatic patients and clinical decisions should be tailored
      individually. 

PMID- 24282694
TI  - Coronary CT angiography with prospective ECG-triggering: an effective alternative
      to invasive coronary angiography.
AB  - Despite the tremendous contributions of coronary CT angiography to coronary
      artery disease, radiation dose associated with coronary CT angiography has raised
      serious concerns in the literature, as the risk of developing radiation-induced
      malignancy is not negligible. Various dose-saving strategies have been
      implemented, with some of the strategies resulting in significant dose reduction.
      Of these strategies, prospective ECG-triggering is one of the most effective
      techniques with resultant effective radiation dose similar to or even lower than
      that of invasive coronary angiography. Prospective ECG-triggered coronary CT
      angiography has been reported to have high diagnostic accuracy in the diagnosis
      of coronary artery disease with image quality comparable to that of retrospective
      ECG-gating, but with significantly reduced radiation dose. Successful performance
      of prospective ECG-triggering is determined by strict exclusion criteria and
      careful patient preparation. The aim of this article is to provide an overview of
      the diagnostic applications of coronary CT angiography with prospective ECG
      triggering with focus on radiation dose reduction. Radiation dose measurements
      are discussed with aim of allowing accurate dose estimation. Diagnostic value of
      prospective ECG-triggered coronary CT angiography in patients with different
      heart rate is discussed. Finally, current status and future directions are
      highlighted. 

PMID- 24282695
TI  - Cardiac rehabilitation past, present and future: an overview.
AB  - Cardiac Rehabilitation has evolved over the past decades from a simple monitoring
      for the safe return to physical activities to a multidisciplinary approach that
      focuses on patient education, individually tailored exercise training,
      modification of the risk factors and the overall well-being of the cardiac
      patients. It has been proven to be an effective tool for the care of the patients
      with heart disease. Recent research in cardiac rehabilitation has demonstrated
      that tremendous benefits can be derived from the optimal use of cardiac
      rehabilitation in patients with various cardiac pathologies including ischemic
      heart disease, heart failure and post heart surgery. The benefits of cardiac
      rehabilitation include mortality reduction, symptom relief, reduction in smoking
      and improved exercise tolerance, risk factors modification and the overall
      psychosocial wellbeing. Unfortunately, cardiac rehabilitation remains
      considerably underutilized mainly because of referral problems and poor
      enrollment. The development of alternate approaches and the use of
      transtelephonic and other means of monitoring and surveillance will help expand
      the utilization of cardiac rehabilitation. 

PMID- 24282696
TI  - Acute coronary syndrome in HIV patients: from pathophysiology to clinical
      practice.
AB  - A majority of human immunodeficiency virus (HIV) infected subjects in developed
      countries have access to highly active anti-retroviral therapy (HAART), which is
      associated with significantly improved long term survival. In this setting,
      clinical attention needs to be focused on the impact of premature atherosclerotic
      cardiovascular disease (CVD), which already represents a leading cause of
      morbidity and mortality in these patients. While the higher prevalence of
      traditional risk factors remains the main culprit of increased CVD risk, HIV
      infection itself and antiretroviral toxicity are confounding proatherogenic
      factors. It is therefore critical to treat modifiable risk factors, keeping close
      attention to drug interactions in these patients with high cardiovascular risk
      profile. 

PMID- 24282697
TI  - Angiotensin II type-2 receptor-specific effects on the cardiovascular system.
AB  - The renin-angiotensin system (RAS) is intricately involved in cardiovascular
      homeostasis. It is well known that angiotensin II, the key effector in RAS,
      contributes to a range of cardiovascular pathologies and diseases via angiotensin
      II type-1 receptor (AT1R) activation. However, the role of angiotensin II type-2
      receptor (AT2R) regulation is less well understood. Recent studies describe the
      role of the AT2R on cardiovascular function in normal and pathologic conditions.
      The data describe an important role of AT2R in blood pressure regulation, cardiac
      hypertrophy and fibrosis, myocardial infarction and vascular homeostasis. 

PMID- 24282698
TI  - 10-years experience with the Athero-Express study.
AB  - From cross-sectional studies we have learned that composition of atherosclerotic
      plaques differs, and that thrombosis on top of an inflammatory lipid rich plaque
      is a frequently observed pathological substrate of a cerebral or coronary event.
      Atherosclerosis develops over decades which hampers human studies on the natural
      history of the diseases. Therefore, the predictive value of atherosclerotic
      plaque composition for development of an adverse cardiovascular event is not
      clear. The elucidation of markers for atherosclerotic disease progression is
      essential to identify patients at high risk for vascular events, to refine
      treatment allocation and to serve as surrogate endpoints in pharmaceutical
      studies. The Athero-Express study is a large scale vascular biobank that collects
      vascular specimens including a clinical follow-up. This study design allows the
      prospective study of the local atherosclerotic plaque in relation to future local
      and systemic vascular outcome. The readout of the study can be assessed in terms
      of histology as well as RNA or protein level. This paper aims to give an overview
      of the results of the Athero-Express biobank since its initiation in 2002. We
      will also discuss the clinical implications and future directions in biobanking
      research. 

PMID- 24282700
TI  - Rusty shelter.

PMID- 24282699
TI  - Lack of focus on cardiovascular disease in sub-Saharan Africa.
AB  - Research into cardiovascular disease in Sub-Saharan Africa has been hampered by
      lack of funding and expertise. However, hospital- and community-based data reveal
      high economic and social costs of these diseases to the national health services
      and the communities, with the region facing a mixed burden of diseases related to
      poverty and infections, emergence of risk factors and diseases of affluence, as
      well as new cardiovascular problems caused by the HIV/AIDS epidemics. The
      availability of echocardiography has raised the profile of these conditions in
      sub-Saharan Africa, stimulating several projects led by local cardiologists under
      the umbrella of the Pan-African Society of Cardiology. This research may help to
      overcome the lack of focus on cardiovascular diseases in Sub-Saharan Africa, as
      well as increase the awareness of the public and policymakers on the burden of
      cardiovascular diseases. 

PMID- 24282701
TI  - 'Longitudinal' topics in Cardiovascular Diagnosis and Therapy (CDT).

PMID- 24282702
TI  - Epicardial and thoracic fat - Noninvasive measurement and clinical implications.
AB  - Epicardial fat, the local visceral fat depot enclosed by the visceral pericardial
      sac, surrounds the coronary arteries for most of their course, and may contribute
      to the development of coronary atherosclerosis through local production of
      inflammatory cytokines. Several studies which measured epicardial fat volume
      noninvasively have shown a relationship of increased epicardial fat volume with
      coronary artery disease, with the presence and progression of coronary plaque,
      major adverse cardiovascular events, myocardial ischemia and atrial fibrillation.
      Quantitative measurement of epicardial fat volume from noninvasive imaging
      modalities such as CT and MRI are feasible, and may play a clinical role in
      cardiovascular risk assessment. The evidence to date warrants larger studies with
      follow-up to further investigate the role of epicardial fat as an imaging marker
      with prognostic importance. 

PMID- 24282703
TI  - Coronary artery calcium scoring, what is answered and what questions remain.
AB  - Coronary artery calcification (CAC) is a widely used imaging modality for
      cardiovascular risk assessment in moderate risk patients. It has been shown to
      have a superior role predicting future cardiac events and survival rates when
      combined with other traditional risk factor scoring systems as Framingham risk
      score (FRS). Furthermore, it significantly reclassifies moderate risk patients
      into lower or higher risk categories. Higher risk groups like patients with
      diabetes, a higher prevalence of CAC has been shown to impart a high short term
      risk of CV events, while those with zero calcium score had excellent event-free
      survival, similar to non-diabetic patients. Having a zero calcium score is
      currently used in United Kingdom practice guidelines (NICE) as a gatekeeper for
      any further investigations in patients presenting to the emergency department
      (ED) with chest pain. Unanswered questions include the concept of CAC progression
      that need to be standardized with respect to technique, interpretation and
      subsequent management strategies. Studies also demonstrated that risk assessment
      using CAC was motivational to patients leading to better adherence to their
      preventive practices as well as medications. However, statin did not consistently
      prove beneficial in slowing the CAC progression rate, but did reduce CV events
      significantly in patients with increased CAC. Accordingly, more studies need to
      be conducted to further help understand the ideal way to utilize this imaging
      tool and decreasing downstream utilization. 

PMID- 24282704
TI  - Non-invasive functional assessment using computed tomography: when will they be
      ready for clinical use?
AB  - Coronary computed tomography (CT) angiography is a noninvasive and accurate
      diagnostic tool to detect coronary artery disease (CAD), and is increasingly
      utilized in clinical practice. However, anatomical information from coronary CT
      angiography does not always provide accurate insight into whether the stenosis
      causes clinically significant ischemia. With a concern that widespread use of
      coronary CT angiography may result in excess referral of patients to invasive
      coronary angiography and unnecessary revascularization of non-ischemic coronary
      lesions, novel methods were developed to evaluate both anatomic and functional
      aspects of coronary stenosis. Several studies suggested that CT assessment of
      myocardial stress perfusion is feasible and improves the diagnostic accuracy of
      coronary CT angiography in the detection of hemodynamically significant stenosis.
      Cardiac CT protocol including both coronary CT angiography and stress/rest
      myocardial perfusion can simultaneously evaluate anatomical CAD and its
      physiological consequences. However, significant radiation exposure and a larger
      volume of iodinated contrast administration are required for additional perfusion
      imaging. Computational fluid dynamics, as applied to coronary CT angiography,
      enables prediction of blood flow and pressure in coronary arteries, and
      calculation of lesion-specific fractional flow reserve (FFR). CT-derived FFR
      (FFRCT) was reported to have a high diagnostic performance for detection and
      exclusion of ischemia-causing stenosis. Since the calculation of FFRCT is
      performed on simulated hyperemia, it does not require modification of typical
      coronary CT angiography protocols, does not require the administration of
      additional medication and does not confer any additional radiation. CT myocardial
      perfusion imaging and CT-derived computed FFR represent significant advances in
      the field of cardiac CT, with the ability to combine anatomical data from CT
      angiography together with the physiologic significance of anatomical stenosis.
      Such non-invasive anatomic-functional testing prior to intervention may improve
      patient outcomes and reduce costs. Further clinical studies are needed prior to
      widespread clinical adoption of these diagnostic techniques. 

PMID- 24282705
TI  - Post myocardial infarction of the left ventricle: the course ahead seen by
      cardiac MRI.
AB  - In the last decades, cardiac magnetic resonance imaging (MRI) has gained
      acceptance in cardiology community as an accurate and reproducible diagnostic
      imaging modality in patients with ischemic heart disease (IHD). In particular, in
      patients with acute myocardial infarction (MI) cardiac MRI study allows a
      comprehensive assessment of the pattern of ischemic injury in term of reversible
      and irreversible damage, myocardial hemorrhage and microvascular obstruction
      (MVO). Myocardial salvage index, derived by quantification of myocardium (area)
      at risk and infarction, has become a promising surrogate end-point increasingly
      used in clinical trials testing novel or adjunctive reperfusion strategies. Early
      post-infarction, the accurate and reproducible quantification of myocardial
      necrosis, along with the characterization of ischemic myocardial damage in its
      diverse components, provides important information to predict post-infarction
      left ventricular (LV) remodeling, being useful for patients stratification and
      management. Considering its non-invasive nature, cardiac MRI suits well for
      investigating the time course of infarct healing and the changes occurring in
      peri-infarcted (adjacent) and remote myocardium, which ultimately promote the
      geometrical, morphological and functional abnormalities of the entire left
      ventricle (global LV remodeling). The current review will focus on the cardiac
      MRI utility for a comprehensive evaluation of patients with acute and chronic IHD
      with particular regard to post-infarction remodeling. 

PMID- 24282706
TI  - Heart failure in patients with normal coronary anatomy: diagnostic algorithm and
      disease pattern of various etiologies as defined by cardiac MRI.
AB  - In a subgroup of patients with acute heart failure coronary artery disease can be
      excluded. To explain symptoms and optimize therapy cardiac magnetic resonance
      (CMR) imaging can contribute to elucidate the underlying pathology in non
      ischemic heart disease. A diagnostic algorithm for the work-up of these patients
      using CMR is suggested. The review discusses various modules of a dedicated CMR
      protocol. It explains diagnostic markers and challenges of CMR imaging in non
      ischemic heart disease. Based on these suggestions the literature in the field is
      reviewed. 

PMID- 24282707
TI  - Impact of Next-Generation Sequencing (NGS) technology on cardiovascular disease
      research.
AB  - In recent years, hundreds of gene loci associated with multiple cardiovascular
      pathologies and traits have been identified through high-throughput Next
      Generation Sequencing (NGS) technology. Due to the increasing efficiency and
      decreasing cost of NGS, rapid progresses anticipated in the field of CVD
      research. This review summarizes the main strategies of CV research with NGS at
      the level of genomics, transcriptomics, epigenetics, and proteomics. 

PMID- 24282709
TI  - African experiences of humanitarian cardiovascular medicine: the Cardiac Centre
      of St. Elizabeth Catholic General Hospital, Shisong.
AB  - The cardiac centre of Shisong inaugurated few years ago is a good example of the
      mobilization of humanitarian resources from the north and south for the
      improvement of cardiovascular diagnosis and treatment in Africa. From the
      inauguration of the Center to December 2011, 23 surgical missions have been
      organized, (5 peadiatric and 18 adults) and 204 patients have been operated with
      the help of the partners: Associazione Bambini Cardiopatici nel Mondo and Cuore
      Fratello. The Catheterisation Laboratory has performed a total of 117 diagnostic
      and interventional procedures while 22 pace makers were implanted (12 single
      chambers and 10 dual-chambers). Many problems and challenges are faced everyday
      but with the enthusiasm, the dynamism and the professional skills of the
      personnel, the help of the partners we see a bright future. 

PMID- 24282710
TI  - Aspirin in primary prevention: can we individualize care?

PMID- 24282711
TI  - Carina shift as a mechanism for side-branch compromise following main vessel
      intervention: insights from three-dimensional optical coherence tomography.

PMID- 24282712
TI  - New data on cardiovascular interventions in China reported.

PMID- 24282713
TI  - The art of nature.

PMID- 24282708
TI  - Cardiac biomarkers: new tools for heart failure management.
AB  - The last decade has seen exciting advances in the field of biomarkers used in
      managing patients with heart failure (HF). Biomarker research has broadened our
      knowledge base, shedding more light on the underlying pathophysiological
      mechanisms occurring in patients with both acute and chronic HF. The criterion
      required by an ideal cardiovascular biomarker has been progressively changing to
      an era of sensitive assays that can be used to guide treatment. Recent
      technological advances have made it possible to rapidly measure even minute
      amounts of these proteins by means of higher sensitivity assays. With a high
      prevalence of comorbidities associated with HF, an integrated approach utilizing
      multiple biomarkers have shown promise in predicting mortality, better risk
      stratification and reducing re-hospitalizations, thus lowering health-care costs.
      This review provides a brief insight into recent advances in the field of
      biomarkers currently used in the diagnosis and prognosis of patients with acute
      and chronic HF. 

PMID- 24282714
TI  - Kaethe Kollwitz's expressions of grief.

PMID- 24282715
TI  - An evolving journal.

PMID- 24282716
TI  - Conflict of interest in Peer-Reviewed medical journals: the World Association of
      Medical Editors (WAME) position on a challenging problem.

PMID- 24282717
TI  - Risk factors of prolonged mechanical ventilation following open heart surgery:
      what has changed over the last decade?
AB  - OBJECTIVE: To identify the risk factors for prolonged invasive mechanical
      ventilation after open heart surgery in Pakistan. DESIGN: This study is based on
      retrospective analysis of database. PLACE AND DURATION: We conducted study of all
      patients who underwent open heart surgery at CPE Institute of Cardiology, Multan
      from March 2009 to May 2011. PATIENTS & METHODS: The data was retrieved from the
      database in the form of electronic spreadsheet which was then analyzed using SPSS
      software. The patients with incomplete data entries were removed from the
      analysis resulting in a set of 1,617 patients. The data of each patient consisted
      of 65 preoperative, operative and postoperative variables. The data was
      summarized as means, medians and standard deviations for numeric variables and
      frequencies and percentages or categoric variables. These risk factors were
      compared using Chi-sqaure test. Their ODDs ratios and 95% confidence intervals of
      ODD's Ratios and P values were calculated. RESULTS: Out of a total of 1,617
      patients, 77 patients (4.76%) had prolonged ventilation for a cumulated duration
      of more than over 24 hours. Preoperative renal failure, emphysema, low EF (<30%),
      urgent operation, preoperative critical state, prolonged bypass time, prolonged
      cross clamp time, complex surgical procedures and peri-operative myocardial
      infarction were found to be risk factors for PIMV. Old age, female gender,
      advanced ASA class, advanced NYHA class, diabetes mellitus, smoking, history of
      COPD, redo surgery, left main stenosis, obesity and use of intra-aortic balloon
      pump were not found to have significant ODDs ratios for PIMV. The patients with
      prolonged ventilation had significantly high mortality i.e. 32.47% while the
      normal ventilation group had 0.32% overall mortality. CONCLUSIONS: Many of the
      previously considered risk factors for prolonged ventilation after open heart
      study are no more significant risk factors. However, prolonged ventilation
      continues to be associated with very high mortality.

PMID- 24282718
TI  - Bone marrow-derived cell therapy in chagasic cardiac disease: a review of pre
      clinical and clinical results.
AB  - Chagas disease is caused by a protozoan parasite Trypanosoma cruzi, which infects
      people through blood sucking insects. It is endemic in Latin America and the
      disease is being spread to developed countries as a result of the migration of
      infected individuals. In its chronic stage, Chagas disease can lead to a severe
      cardiomyopathy for which there is currently no cure. End-stage patients require
      heart transplantation, thus demanding new therapeutic modalities. Cell-based
      therapy has been proposed as an alternative for various forms of heart disease.
      Here we review the experimental evidence that led to the use of bone marrow
      derived cells in putative therapy for chronic chagasic cardiomyopathy in animal
      models and in clinical trials, discussing the reasons for failure of the
      translation of results from mice to men. 

PMID- 24282719
TI  - Imaging in the context of replacement heart valve development: use of the Visible
      Heart((r)) methodologies.
AB  - In recent years huge strides have been made in the fields of interventional
      cardiology and cardiac surgery which now allow physicians and surgeons to repair
      or replace cardiac valves with greater success in a larger demographic of
      patients. Pivotal to these advances has been significant improvements in cardiac
      imaging and improved fundamental understanding of valvular anatomies and
      morphologies. We describe here a novel series of techniques utilized within the
      Visible Heart((r)) laboratory by engineers, scientists, and/or anatomists to
      visualize and analyze the form and function of the four cardiac valves and to
      assess potential repair or replacement therapies. The study of reanimated large
      mammalian hearts (including human hearts) using various imaging modalities, as
      well as specially prepared anatomical specimens, has enhanced the design,
      development, and testing of novel cardiac therapies. 

PMID- 24282720
TI  - African experiences of humanitarian cardiovascular medicine: a Kenyan
      perspective.
AB  - The burden of cardiovascular diseases (CVD) is on the rise in Kenya; this is in
      tandem with that of other non-communicable diseases. Most cardiovascular services
      are available in the main cities (Nairobi and Mombasa), but almost non-existent
      in rural and other urban centers. In an attempt to bridge this gap on service
      delivery, humanitarian activities have been developed over the years by various
      interested parties. Three models of humanitarian activities are described. The
      first model (hereby referred to as Model 1) is a school-based rheumatic fever and
      rheumatic heart disease (RF/RHD) prevention outreach program which offers
      diagnostic, preventive, educational and curative services to primary and
      secondary school children in various parts of the country. The second model
      (hereby referred to as Model 2) is a hospital-based cardiovascular outreach
      program located in Kericho, a highland tea growing region that has long been
      perceived as a "hot spot" for CVD. The third model (hereby referred to as Model
      3) is a fixed clinic-based cardiovascular outreach in Kisumu, the lake shore
      town, about 400 kilometers west of Nairobi. THESE PROGRAMS PROVIDE: prevention
      services, early detection and prophylaxis, facilitation for further treatment,
      follow-up, early disease management, staff motivation, training in basic
      cardiology skills and increased local awareness of CVD to clinicians in there far
      flung centers. Data from these programs is also presented, with two of the
      programs reporting Kericho County as a 'hot spot' in RF/RHD. Despite various
      challenges, the future is still bright with sustainable initiatives.

PMID- 24282721
TI  - The specialty of pulmonary vascular medicine in China: historical development and
      future directions.
AB  - Over the past 40 years, Chinese experts have made great progress on research,
      diagnosis, and therapy of pulmonary vascular disease, including pulmonary
      embolism and pulmonary hypertension. These theoretical and clinical advances have
      increased public awareness about this group of conditions, which are associated
      with significant morbidity and mortality in China and worldwide. With its
      theoretical basis combining knowledge from cardiovascular and pulmonary medicine,
      pulmonary vascular disease has developed into a separate, unique specialty in
      hospitals across China and worldwide. This article will provide a short
      historical perspective but also an outlook into the future of this exciting novel
      discipline. We provide a Chinese perspective, based on our research and clinic
      experience over the past decades. 

PMID- 24282722
TI  - African experiences of humanitarian cardiovascular medicine: the Mozambican
      experience.

PMID- 24282723
TI  - European creativity and American experience.

PMID- 24282724
TI  - Medical publishing in a digital world: New World, new standards?

PMID- 24282725
TI  - Fractional flow reserve measurements to identify justified targets for PCI in
      patients with stable angina: FAME 2 and beyond.

PMID- 24282726
TI  - Treating stable ischemic heart disease with percutaneous coronary intervention -
      The debate continues.

PMID- 24282727
TI  - Reproducibility of myocardial perfusion reserve - variations in measurements from
      post processing using commercially available software.
AB  - PURPOSE: Adenosine stress first pass cardiac magnetic resonance imaging (CMRI) is
      a rapidly evolving tool in the diagnosis of ischemic heart disease (IHD). The
      rest and stress first pass myocardial perfusion data may be interpreted using
      commercially available software for calculation of time intensity curves in order
      to generate a numeric value of the segmental or whole heart myocardial perfusion
      reserve index (MPRI). The objective of this study was to determine the inter- and
      intra-observer reliability of the data generated by standard commercially
      available software. METHODS: Data from 20 adenosine stress CMRI (1.5 T) studies
      were analyzed using commercially available CAAS MRV 3.3 software (Pie Medical
      Imaging B.V., Netherlands) for calculation of the MPRI. The stress CMRI was
      performed using a standardized protocol in 20 women including 10 women with
      angina and the absence of obstructive CAD and 10 healthy volunteers. MPRI
      calculation was made in a standardized manner on separate occasions by two
      independent observers. A single observer repeated the calculation of MPRI three
      months later, without reference to the prior data. Basal, mid, and apical
      segments, for the whole myocardium, sub-endocardium, and sub-epicardium were
      analyzed. Intra-class correlation coefficients (ICC), repeatability coefficients
      (RC), and coefficients of variation (CoV) were determined. RESULTS: The MPRI
      results by repeated software measurements were highly correlated, with
      potentially important variations in measurement observed. The myocardial inter
      observer ICC was 0.80 (95% CI, 0.57, 0.92) with a CoV of 7.5%, and intra-observer
      ICC was 0.89 (95% CI, 0.77, 0.95) with a CoV of 3.6%. The mid-ventricular level
      MPRI was most reproducible, with intra-observer ICC at 0.91 (95% CI, 0.77, 0.97);
      intra-observer measurement was more reproducible than inter-observer measurement.
      CONCLUSIONS: There is variation in measurement of MPRI observed in post
      processing of perfusion data when using a standardized approach and commercially
      available software. This has implications in the interpretation of data obtained
      for clinical and research purposes.

PMID- 24282728
TI  - The cardiac hypoxic niche: emerging role of hypoxic microenvironment in cardiac
      progenitors.
AB  - Resident stem cells persist throughout the entire lifetime of an organism where
      they replenishing damaged cells. Numerous types of resident stem cells are housed
      in a low-oxygen tension (hypoxic) microenvironment, or niches, which seem to be
      critical for survival and maintenance of stem cells. Recently our group has
      identified the adult mammalian epicardium and subepicardium as a hypoxic niche
      for cardiac progenitor cells. Similar to hematopoietic stem cells (LT-HSCs),
      progenitor cells in the hypoxic epicardial niche utilize cytoplasmic glycolysis
      instead of mitochondrial oxidative phosphorylation, where hypoxia inducible
      factor 1alpha (Hif-1alpha) maintains them in glycolytic undifferentiated state.
      In this review we summarize the relationship between hypoxic signaling and stem
      cell function, and discuss potential roles of several cardiac stem/progenitor
      cells in cardiac homeostasis and regeneration. 

PMID- 24282729
TI  - Microwave radiometry: a new non-invasive method for the detection of vulnerable
      plaque.
AB  - Atherosclerosis and its consequences are the most rapidly growing vascular
      pathology, with myocardial infarction and ischemic cerebrovascular accident to
      remain a major cause of premature morbidity and death. In order to detect the
      morphological and functional characteristics of the vulnerable plaques, new
      imaging modalities have been developed. Intravascular thermography (IVT) is an
      invasive method, which provides information on the identification of the high
      risk atheromatic plaques in coronary arteries. However, the invasive character of
      IVT excludes the method from primary prevention. Microwave radiometry (MR) is a
      new non-invasive method, which detects with high accuracy relative changes of
      temperature in human tissues whereas this thermal heterogeneity is indicative of
      inflammatory atherosclerotic plaque. Both experimental and clinical studies have
      proved the effectiveness of MR in detecting vulnerable plaque whereas recent
      studies have also revealed its association with plaque neoangiogenesis as
      assessed by contrast enhanced carotid ultrasound (CEUS). 

PMID- 24282732
TI  - Emblem of death.

PMID- 24282730
TI  - Antioxidant therapies for the management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice, representing a major public health problem. Recent evidence suggests
      oxidative stress may play an important role in the pathogenesis and perpetuation
      of AF. In the past few years, experimental data and clinical evidence have tested
      the concept of antioxidant therapies to prevent AF. Besides statins, ACE
      inhibitors (ACEIs) and/or angiotensin-receptor blockers (ARBs), and omega-3
      polyunsaturated fatty acids, several other interventions with antioxidant
      properties, such as Vitamin C and E, thiazolidinediones, N-acetylcysteine,
      probucol, nitric oxide donors or precursors, NADPH oxidase inhibitors, Xanthine
      oxidase inhibitors have emerged as novel strategies for the management of AF. We
      aim to review recent evidence regarding antioxidant therapies in the prevention
      and treatment of atrial fibrillation. 

PMID- 24282731
TI  - The Popeye domain containing genes: essential elements in heart rate control.
AB  - The Popeye domain containing (Popdc) gene family displays preferential expression
      in skeletal muscle and heart. Only recently a significant gain in the
      understanding of the function of Popdc genes in the heart has been obtained. The
      Popdc genes encode membrane proteins harboring an evolutionary conserved Popeye
      domain, which functions as a binding domain for cyclic adenosine monophosphate
      (cAMP). Popdc proteins interact with the two-pore channel TREK-1 and enhance its
      current. This protein interaction is modulated by cAMP. Null mutations of members
      of the Popdc gene family in zebrafish and mouse are associated with severe
      cardiac arrhythmia phenotypes. While in zebrafish an atrioventricular block was
      prevalent, in mouse a stress-induced sinus bradycardia was observed, which was
      due to the presence of sinus pauses. Moreover, the phenotype develops in an age
      dependent manner, being absent in the young animal and becoming increasingly
      severe, as the animals grow older. This phenotype is reminiscent of the sick
      sinus syndrome (SSS), which affects mostly the elderly and is characterized by
      the poor ability of the cardiac pacemaker to adapt the heart rate to the
      physiological demand. While being a prevalent disease, which is responsible for a
      large fraction of pacemaker implantations in Western countries, SSS is poorly
      understood at the molecular level. It is therefore expected that the study of the
      molecular basis of the stress-induced bradycardia in Popdc mice will shed new
      light on the etiology of pacemaker disease. 

PMID- 24282733
TI  - Clay sculpture.

PMID- 24282734
TI  - Transapical aortic valve implantation - What have we learnt? Quo vadis?

PMID- 24282735
TI  - The EASE trial: surgery for infective endocarditis, have we found the right
      timing?

PMID- 24282736
TI  - NSW public hospitals accessing digital radiology images.

PMID- 24282737
TI  - Transapical transcatheter aortic valve implantation: the front door approach
      captures the world.

PMID- 24282738
TI  - Learning experience with transapical aortic valve implantation - the initial
      series from Leipzig.

PMID- 24282739
TI  - Kounis syndrome: a monster for the atopic patient.

PMID- 24282740
TI  - A peripheral blood gene expression score is associated with plaque volume and
      phenotype by intravascular ultrasound with radiofrequency backscatter analysis:
      results from the ATLANTA study.
AB  - BACKGROUND: A composite, peripheral gene expression score based on quantitative
      RNA-measurements has been validated for detecting stenosis against invasive
      coronary X-ray angiography. IVUS/VH has been validated for quantitative
      measurements of coronary plaque volume and composition and has been shown to be
      predictive of outcomes and treatment effects. The correlation between peripheral
      gene expression and coronary plaque composition by intravascular ultrasound with
      radiofrequency backscatter (IVUS/VH) is unknown. METHODS: Peripheral blood gene
      expression score (GES) was prospectively measured in 18 patients undergoing
      IVUS/VH. Plaque volume and composition [fibrous tissue (FI), fibro-fatty tissue
      (FF), necrotic core (NC) and dense calcium (DC)] were quantified in 3 dimensions
      in all plaques within the entire pullback. The relationship to GES was assessed
      by Spearman rank correlation. RESULTS: Mean age was 61.1+/-8.6 years; 67% were
      male. 1,158 mm of coronary anatomy was imaged by IVUS/VH. Using a validated scale
      of 1-40, mean GES was 21.6+/-9.4. GES was associated with plaque volume
      (R(2)=0.55; P=0.018), NC volume (R(2)=0.56; P=0.015), DC volume (R(2)=0.60;
      P=0.007), and non-calcified plaque volume (R(2)=0.50; P=0.036) by Spearman rank
      correlation. CONCLUSIONS: In this preliminary report, increased GES was
      associated with higher plaque volume and a more vulnerable plaque phenotype as
      evidenced by NC and DC. This composite GES is not only associated with
      obstructive coronary disease, but also with higher plaque volume and vulnerable
      phenotype.

PMID- 24282741
TI  - Aortic regurgitation after transcatheter aortic valve implantation: mechanisms
      and implications.
AB  - In recent years, transcatheter aortic valve implantation (TAVI) has become an
      established treatment option for selected high-risk patients with severe aortic
      stenosis (AS). Favorable results with regard to both hemodynamics and clinical
      outcome have been achieved with transcatheter valves. Aortic regurgitation (AR)
      remains a major concern after TAVI. Echocardiography is the imaging modality of
      choice to assess AR in these patients due to its wide accessibility and low cost.
      Mostly mild residual AR has been observed in up to 70% of patients. However, as
      even a mild degree of AR has been associated with a decreased survival up to two
      years after TAVI, accurate evaluation and classification of AR is important. AR
      in transcatheter valves can be divided into three types according to different
      pathophysiological mechanisms. Besides the well-known transvalvular and
      paravalvular forms of regurgitation, a third form termed supra-skirtal has
      recently been observed. A thorough understanding of AR in transcatheter valves
      may allow to improve device design and implantation techniques to overcome this
      complication. The aim of this review is to provide an overview of the three types
      of AR after TAVI focussing on the different pathophysiological mechanisms. 

PMID- 24282744
TI  - Kounis syndrome - an atopic monster for the heart.

PMID- 24282742
TI  - High residual platelet reactivity on clopidogrel: its significance and
      therapeutic challenges overcoming clopidogrel resistance.
AB  - Over the last decade, dual antiplatelet therapy has been the mainstay of the
      management of Acute Coronary Syndrome, with clopidogrel therapy providing clear
      benefits over aspirin monotherapy and becoming the agent of choice for the
      prevention of stent thrombosis. While newer antiplatelet agents have now become
      available, clopidogrel is still widely used due to its low cost and efficacy.
      However, many patients still experience recurrent ischemic events. A poor
      response of the platelets to clopidogrel, called High Residual Platelet
      Reactivity (HRPR), has been incriminated to account for this dilemma. Despite the
      absence of a universal definition of HRPR or the gold standard test to quantify
      it, persistent high platelet reactivity has consistently been associated with
      recurrence of ischemic events. Clopidogrel metabolism is highly variable, and
      genetics, comorbidities and drug interactions can affect it. In this article we
      review all definitions of HRPR, explore the available tests to quantify it, the
      clinical outcomes associated with it, as well as strategies that have shown
      success in overcoming it. 

PMID- 24282743
TI  - Contemporary echocardiographic guiding tools for device closure of interatrial
      communications.
AB  - Periinterventional echocardiographic guidance is considered desirable in order to
      make interventional closure of interatrial communications safe and straight
      forward. Transesophageal echocardiography (TEE) including real-time three
      dimensional (RT-3D) imaging, later complemented and in part replaced by
      intracardiac echocardiography (ICE), has become established as the standard
      approach to guide those procedures. Especially in atrial septal defect (ASD)
      closure, which tends to be more challenging than patent foramen ovale (PFO)
      closure, a certain risk of severe complications remains and may result from
      suboptimal device performance. Other complications may be related to
      discontinuous use of echocardiographic monitoring. Image fusion and RT-3D ICE are
      currently under clinical testing and might be suitable to facilitate spatial
      orientation. Nowadays, two-dimensional ICE is the method of choice for guiding
      percutaneous device closure, especially of ASDs and "complex" PFOs. Uninterrupted
      TEE under deep sedation is an alternative. In contrast, closure of "simple" PFOs
      will often require nothing but final confirmation of the result, and therefore,
      short echocardiographic viewing is sufficient in many cases. 

PMID- 24282746
TI  - Neuro sculpture.

PMID- 24282745
TI  - Large atrial myxoma mimicking severe mitral stenosis associated with right heart
      enlargement and severe pulmonary hypertension.

PMID- 24282747
TI  - Embroidering the microscopic world.

PMID- 24282748
TI  - Clinical applications of the areas under ESPVR.

PMID- 24282749
TI  - A pedometer-based physical activity intervention for patients entering a
      maintenance cardiac rehabilitation program: a pilot study.
AB  - PURPOSE: To compare the effects of an individualized pedometer-driven physical
      activity (PA) intervention with the usual time-based PA recommendations given to
      patients entering a maintenance cardiac rehabilitation (CR) program. METHODS: A
      total of 18 subjects entering a maintenance CR program were recruited and
      completed the study. Subjects were randomized into pedometer feedback [PF: n=10
      (2 women), 53.3+/-8.1 yrs] and usual care [UC: n=8 (2 women), 59.4+/-9.9 yrs]
      groups. New Lifestyles NL-1000 pedometers were used to monitor ambulatory PA.
      Subjects in both groups participated in the same maintenance CR program for a
      total of 8 weeks and all were encouraged to obtain a minimum of 30-40 min/d of
      moderate-vigorous-intensity physical activity (MVPA), on days they did not attend
      CR. Subjects in the PF group were given individualized daily stepcount goals
      (increase 10% of baseline steps/d each week) for weeks 2-8. Ambulatory PA was
      measured with pedometers, recording both total number of steps/d and min/d of
      MVPA. Measures were obtained during the first week of the maintenance CR program
      and during the 8th week. Data were also compared between days subjects attended
      and on days they did not attend. RESULTS: By the 8th week of CR, PF subjects
      increased daily stepcounts by 42% (2,297+/-1,606 steps/d, P=0.001), with a 36%
      increase on CR days (2,654+/-2,089 steps/d, P=0.003) and a 45% increase on days
      they did not attend CR (1,872+/-2,026 steps/d, P=0.017). There were no changes
      observed in the UC group. CONCLUSIONS: Providing pedometers with individualized
      stepcount goals to patients entering a CR program was superior to the usual time
      based PA recommendations for increasing PA.

PMID- 24282750
TI  - Advanced 3-D analysis, client-server systems, and cloud computing-Integration of
      cardiovascular imaging data into clinical workflows of transcatheter aortic valve
      replacement.
AB  - Degenerative aortic stenosis is highly prevalent in the aging populations of
      industrialized countries and is associated with poor prognosis. Surgical valve
      replacement has been the only established treatment with documented improvement
      of long-term outcome. However, many of the older patients with aortic stenosis
      (AS) are high-risk or ineligible for surgery. For these patients, transcatheter
      aortic valve replacement (TAVR) has emerged as a treatment alternative. The TAVR
      procedure is characterized by a lack of visualization of the operative field.
      Therefore, pre- and intra-procedural imaging is critical for patient selection,
      pre-procedural planning, and intra-operative decision-making. Incremental to
      conventional angiography and 2-D echocardiography, multidetector computed
      tomography (CT) has assumed an important role before TAVR. The analysis of 3-D CT
      data requires extensive post-processing during direct interaction with the
      dataset, using advance analysis software. Organization and storage of the data
      according to complex clinical workflows and sharing of image information have
      become a critical part of these novel treatment approaches. Optimally, the data
      are integrated into a comprehensive image data file accessible to multiple groups
      of practitioners across the hospital. This creates new challenges for data
      management requiring a complex IT infrastructure, spanning across multiple
      locations, but is increasingly achieved with client-server solutions and private
      cloud technology. This article describes the challenges and opportunities created
      by the increased amount of patient-specific imaging data in the context of TAVR. 

PMID- 24282751
TI  - Global Environmental Threats: why they are hard to see and how a medical model
      may contribute to their understanding.

PMID- 24282752
TI  - Cardiac tamponade due to the rupture of the coronary artery fistula.

PMID- 24282753
TI  - Caseous calcification of mitral annulus.

PMID- 24282754
TI  - Warfarin and aspirin for primary prevention in patients with heart failure in
      sinus rhythm.

PMID- 24282755
TI  - The nature of growth.

PMID- 24282756
TI  - The power of painting.

PMID- 24282757
TI  - Caseous calcification of the mitral annulus.
AB  - A 61-year-old asymptomatic woman was referred for echocardiography to evaluate
      recently detected systolic murmur. Transthoracic echocardiography revealed an
      echodense obstructive mass in the left ventricular outflow tract of unclear
      origin. Subsequent transesophageal echo suggested an intracardiac calcified tumor
      and recommended surgical excision. Contrast-enhanced cardiac computed tomography
      (CT) confirmed a well-defined lobulated mass adherent to the anterior mitral
      valve leaflet, the non-enhanced scout view revealed marked hyper-attenuation
      confirming diffuse calcification. Caseous calcification was diagnosed and surgery
      was deferred. Caseous calcification is typically benign and most commonly
      involves the posterior mitral annulus. Our patient displayed an atypical location
      of exuberant mitral annular calcification. 

PMID- 24282758
TI  - A new cardiac variable identified?
AB  - Women with suspected cardiac syndrome X (CSX) are difficult to diagnosis and
      treat by conventional means. The women's ischemic syndrome evaluation (WISE)
      study, which started as an exploration of ischemic heart disease, increasingly
      focused on CSX, and two papers that represent an outgrowth and extension of this
      work are featured in this issue. Cardiovascular magnetic resonance imaging (CMRI)
      can generate a myocardial perfusion reserve index (MPRI) that is shown to be
      lower in women with CSX compared to normal controls. The MPRI is a ratio of
      resting to vasodilatation myocardial perfusion uptake and is relatively easy to
      measure. There is growing evidence that the CMRI measured MPRI provides unique
      information that should be regarded as a primary indicator of CSX disease
      severity. The papers describe the low levels of MPRI in a well documented CSX all
      female patient population. The context of this work and its relationship to other
      findings is discussed with an emphasis on the unique information that CMRI can
      provide. 

PMID- 24282759
TI  - Fractional flow reserve guided revascularization in daily practice: clinical
      judgment does not always meet science.
AB  - Measurement of the fractional flow reserve (FFR) during invasive coronary
      angiography is the accepted ''gold standard'' for assessing the functional
      significance of coronary artery lesions by determination of the characteristics
      of blood flow proximal and distal to a coronary stenosis during pharmacologically
      mediated hyperemia. Abnormal FFR is associated with higher cardiac event rate if
      the coronary lesion is left untreated. On the other hand, it was shown that
      patients derived no clinical benefit from revascularization of angiographically
      obstructive lesions which were hemodynamically insignificant according to FFR
      (>0.8). This editorial comment refers to an observational cohort study which
      reported that in approximately 20% of real world patients the treatment strategy
      chosen was discordant with FFR findings. Our comment discusses these findings and
      concludes that while the standard of care is to treat patients in accordance with
      their FFR results (when available), it should be recognized that there are some
      clinical scenarios that may require a treatment strategy that is discordant with
      FFR result. 

PMID- 24282760
TI  - Thoracic aorta cardiac-cycle related dynamic changes assessed with a 256-slice CT
      scanner.
AB  - OBJECTIVE: The aim of our study was to demonstrate whether the dynamic changes
      previously documented at the ascending and abdominal aorta are replicated at the
      thoracic aorta. METHODS AND RESULTS: A consecutive series of thirty patients
      referred to our institution to undergo CT angiography of the thoracic aorta (CTA)
      constituted the study population. Patients with diffuse aortic atherosclerosis
      were excluded from the analysis. All studies were acquired with a 256-MDCT
      scanner and ECG-gating was performed in all cases. Two orthogonal imaging planes
      (maximal and minimal diameters) were obtained at three different levels of the
      descending thoracic aorta, using the distance from the left subclavian artery as
      proximal landmark: 10, 40, and 80 mm distance. The mean age was 58.9+/-15.7 years
      and 16 (53%) patients were male. Descending aorta measurements at 10, 40, and 80
      mm distance from the left subclavian artery were all significantly larger within
      the systolic window (P<0.01 for all comparisons). Measurements of the maximal
      diameter were systematically larger than the minimal diameters among all aortic
      positions including ungated, systolic, and diastolic measurements (P<0.05 for all
      comparisons). CONCLUSIONS: The main finding of our pilot investigation was that
      the thoracic descending aorta undergoes significant conformational changes during
      the cardiac cycle, irrespective from the distance from the left subclavian
      artery.

PMID- 24282761
TI  - Discrepancies between two lipid-lowering guidelines for CVD prevention in
      seemingly healthy individuals-case study Lebanon.
AB  - BACKGROUND: In deciding on optimal interventions for cardiovascular disease (CVD)
      prevention, more than one set of guidelines are available. HYPOTHESIS: The aim of
      the study was to assess the agreement between the European Society of Cardiology
      (ESC) 2011 Guidelines for CVD Prevention and the Canadian Cardiovascular Society
      (CCS) 2009 Guidelines in recommending lipid lowering interventions in a seemingly
      healthy cohort of Lebanese persons. METHODS: A nationally representative cohort
      of Lebanon was identified according to the World Health Organization (WHO) Steps
      Criteria. From this cohort, a group of 283 adult individuals not known to have
      chronic illnesses was selected. Using the algorithms present in each guideline,
      lipid lowering recommendations for each individual were determined. Agreement
      between the two guideline recommendations was determined using the Kappa test.
      RESULTS: As per ESC, 3.9% of the participants required immediate drug therapy,
      15.5% should be considered for drug therapy, and 80.1% required lifestyle
      intervention. As per the CCS, however, 19.4% required drug therapy. The overall
      level of agreement between the ESC and CCS for recommending lipid lowering was
      moderate (Kappa 0.77), and better in males (Kappa 0.82). In contrast, 37.5% of
      females recommended drug therapy as per the CCS guidelines would not be per the
      ESC guidelines (Kappa 0.63). CONCLUSIONS: Significant discrepancies exist in
      recommendations for lipid-lowering therapy between CCS and ESC guidelines when
      applied to Lebanese individuals, particularly for women. Local healthcare
      authorities and the WHO should attend to this issue in order to unify treatment
      approaches and limit disparities in care.

PMID- 24282762
TI  - Fractional flow reserve application in everyday practice: adherence to clinical
      recommendations.
AB  - Fractional flow reserve (FFR) is considered the gold standard for invasive
      assessment of functional, significant coronary stenosis. Nevertheless, its
      application and outcome in daily practice is rarely reported. We investigated
      whether decisions in clinical practice adhered to FFR-generated recommendations
      and whether FFR influenced cardiovascular outcomes. This retrospective,
      observational, cohort study included 189 patients that underwent FFR measurements
      during coronary angiography at our institution The median follow up was 27 months
      (range, 7-112 months). Clinical outcomes (up to 2 years) included all-cause
      mortality, cardiac-mortality, and major adverse cardiac events (MACE) which
      comprised cardiac mortality, non-fatal MI, target vessel revascularization, and
      coronary artery bypass graft (CABG). Patients most frequently presented with
      unstable angina (74.6%). Only 55 patients (29.1%) exhibited significant
      functional stenosis (FFR <=0.8). Nevertheless, 68 patients (36%) underwent
      immediate coronary interventions; 64% were deferred from revascularization
      procedures and managed conservatively with optimal medical treatment. Thirty-five
      patients (18.5%) were treated in discordance with FFR results, but the overall
      MACE rate was similar to that of patients treated in concordance with FFR results
      (8.3% vs. 8.6%, P=0.41). In conclusion, in our everyday practice, the operator's
      decision was in discordance to the FFR measurements and indications in nearly 20%
      of cases. In these selected cases, the operator's subjective judgment may
      continue to play an important role. 

PMID- 24282763
TI  - Cardiac risk factors and myocardial perfusion reserve in women with microvascular
      coronary dysfunction.
AB  - Women with myocardial ischemia without obstructive coronary artery disease (CAD)
      often have microvascular coronary dysfunction (MCD). Traditional cardiac risk
      factors (RFs) contribute modestly to MCD detected by invasive coronary reactivity
      testing (CRT). Cardiac magnetic resonance imaging (CMRI) is an emerging
      noninvasive technique used to evaluate MCD. We evaluated RFs related to CMRI
      myocardial perfusion in women with MCD. 53 women with CRT confirmed MCD underwent
      adenosine stress and rest CMRI (1.5 Tesla). The myocardial perfusion reserve
      index (MPRI) was calculated (Pie Medical) with lower MPRI meaning less perfusion
      reserve. Relationships between RFs and MPRI were examined. The mean age was 54+/
      10 years with a mean body mass index (BMI) of 26.2+/-4.2. The mean MPRI was
      1.63+/-0.39. Hypertension, dyslipidemia, elevated BMI, and post-menopausal status
      were inversely related to MPRI, while ever smoking, age, family history of CAD,
      history of irregular menses, and history of menopausal hormone therapy (MHT) or
      oral contraceptive (OC) use were not. Dyslipidemia and BMI remained significant
      independent predictors of MPRI. Regression modeling demonstrated that the RFs of
      dyslipidemia, obesity, hypertension, family history of CAD, and history of
      irregular menses explained 27% of the observed MCD variance. CONCLUSIONS: In
      conclusion, impaired MPRI measured by CMRI is related to dyslipidemia and
      elevated BMI in women with MCD. These results suggest traditional RFs contribute
      modestly to MCD; a larger cohort of women with MCD should be examined to confirm
      and extend these observations. The impact of traditional CAD RF modification
      strategies, including optimal medical therapy, should be explored as MCD
      treatment targets.

PMID- 24282764
TI  - Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment
      in women with microvascular coronary dysfunction and reference controls.
AB  - OBJECTIVE: We sought to comparatively assess cardiac magnetic resonance imaging
      (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed
      microvascular coronary dysfunction (MCD) cases and reference control women.
      BACKGROUND: Women with signs or symptoms of myocardial ischemia in the absence of
      obstructive coronary artery disease (CAD) frequently have MCD which carries an
      adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT).
      Adenosine CMRI is a non-invasive test that may be useful for the detection of
      MCD. METHODS: Fifty-three women with MCD confirmed by CRT and 12 age- and
      estrogen-use matched reference controls underwent adenosine CMRI. CMRI was
      assessed for MPRI, calculated using the ratio of myocardial blood flow at
      hyperemia/rest for the whole myocardium and separately for the 16 segments as
      defined by the American Heart Association. Statistical analysis was performed
      using repeated measures ANOVA models. RESULTS: Compared to reference controls,
      MCD cases had lower MPRI values globally and in subendocardial and subepicardial
      regions (1.63+/-0.39 vs. 1.98+/-0.38, P=0.007, 1.51+/-0.35 vs. 1.84+/-0.34,
      P=0.0045, 1.68+/-0.38 vs. 2.04+/-0.41, P=0.005, respectively). A perfusion
      gradient across the myocardium with lower MPRI in the subendocardium compared to
      the subepicardium was observed for both groups. CONCLUSIONS: Women with MCD have
      lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be
      a useful diagnostic modality for MCD. Prospective validation of a diagnostic
      threshold for MPRI in patients with MCD is needed.

PMID- 24282765
TI  - Progression of coronary atherosclerosis in African-American patients.
AB  - BACKGROUND: African-Americans with coronary artery disease (CAD) demonstrate
      worse clinical outcomes than Caucasians. While this is partly due to a lack of
      accessibility to established therapies, the mechanisms underlying this difference
      remain to be elucidated. We aimed to characterize the progression of coronary
      atherosclerosis in African-Americans with CAD. METHODS: 3,479 patients with CAD
      underwent serial intravascular ultrasound (IVUS) imaging to evaluate atheroma
      progression in 7 clinical trials of anti-atherosclerotic therapies. Risk factor
      control and atheroma progression were compared between African-Americans (n=170)
      and Caucasians (n=3,309). RESULTS: African-Americans were more likely to be
      female (51.8% vs. 28.1%, P<0.001), have a higher body mass index (32.8+/-6.0 vs.
      31.3+/-5.8 kg/m(2), P=0.002) and greater history of hypertension (85.9% vs.
      78.8%, P=0.02), diabetes (41.8% vs. 30.6%, P=0.002) and stroke (12.9% vs. 3.0%,
      P<0.001). Despite a high use of anti-atherosclerotic medications (93% statin, 89%
      aspirin, 79% beta-blocker, 52% ACE inhibitor), African-Americans demonstrated
      higher levels of LDL-C (2.4+/-0.7 vs. 2.2+/-0.7 mmol/L, P=0.006), CRP (2.9 vs.
      2.0 mg/dL, P<0.001) and systolic blood pressure (133+/-15 vs. 129+/-13 mmHg,
      P<0.001) at follow-up. There was no significant difference in atheroma volume at
      baseline (189.0+/-82.2 vs. 191.6+/-83.3 mm(3), P=0.82) between two groups. Serial
      evaluation demonstrated a greater increase in atheroma volume in African
      Americans (0.51+/-2.1 vs. -3.1+/-1.7 mm(3), P=0.01). This difference persisted
      with propensity matching accounting for differences in risk factor control (0.1+/
      2.1 vs. -3.7+/-1.7 mm(3), P=0.02). CONCLUSIONS: African-Americans with CAD
      achieve less optimal risk factor control and greater atheroma progression. These
      findings support the need for more intensive risk factor modification in African
      Americans.

PMID- 24282766
TI  - Left ventricular noncompaction cardiomyopathy.

PMID- 24282767
TI  - Not quite an acute ST segment elevation myocardial infarction.

PMID- 24282768
TI  - Aortic valve repair with autologous pericardium for traumatic aortic valve
      regurgitation.
AB  - We present a case of successful aortic valve repair for traumatic aortic valve
      regurgitation. A 26-year-old male who had a history of motor-cycle accident
      months prior to admission, was referred to our hospital for surgical treatment of
      severe aortic valve regurgitation. Intraoperative inspection revealed a tear in
      noncoronary cusp, with otherwise preserved valvular anatomy. Aortic valvuloplasty
      was successfully performed with closure using an autologous pericardium patch.
      Intraoperative transesophageal echocardiogram confirmed absence of residual
      regurgitation. 

PMID- 24282769
TI  - Abstract landscapes.

PMID- 24282770
TI  - Cleveland, euclid avenue.

PMID- 24282771
TI  - The art of pollination.

PMID- 24282772
TI  - Ultrasound a new paradigm in regional anesthesia and pain management.

PMID- 24282773
TI  - Analgesic Effects of Intravenous Ketamine during Spinal Anesthesia in Pregnant
      Women Undergone Caesarean Section; A Randomized Clinical Trial.
AB  - BACKGROUND: Suitable analgesia after cesarean section helps mothers to be more
      comfortable and increases their mobility and ability to take better care of their
      infants. OBJECTIVES: Pain relief properties of ketamine prescription were
      assessed in women with elective cesarean section who underwent spinal anesthesia
      with low dose intravenous ketamine and midazolam and intravenous midazolam alone.
      PATIENTS AND METHODS: Sixty pregnant women scheduled for spinal anesthesia for
      cesarean section were randomized into two study groups. Ketamine (30 mg) +
      midazolam (1 mg = 2CC) or 1mg midazolam (2CC) alone, was given immediately after
      spinal anesthesia. Pain scores at first, second and third hours after CS
      operation, analgesic requirement and drug adverse effects were recorded in all
      patients. RESULTS: Ketamine group had significant pain relief properties in
      compare with control group in first hours after cesarean section (0.78 +/- 1.09
      vs. 1.72 +/- 1.22, VAS score, P = 0.00). Total dose of meperidine consumption in
      women of ketamine group was significantly lower than women of control group
      (54.17 +/- 12.86 vs. 74.44 +/- 33.82 mg, P = 0.02). There were no significant
      drug side effects in participated patients. CONCLUSIONS: Intravenous low-dose
      ketamine combined with midazolam for sedation during spinal anesthesia for
      elective Caesarean section provides more effective and long lasting pain relief
      than control group.

PMID- 24282774
TI  - Comparison of surgical conditions during propofol or isoflurane anesthesia for
      endoscopic sinus surgery.
AB  - BACKGROUND: The Anesthesia planning is an important and determining factor in the
      amount of intraoperative hemorrhage, which can affect the rate of intraoperative
      and postoperative complications. OBJECTIVES: In this study we used two different
      anesthesia techniques in functional endoscopic sinus surgery (FESS) and compared
      the amount of hemorrhage in the two groups. PATIENTS AND METHODS: In a single
      blind clinical trial, 44 patients with ASA class I and II candidate for FESS in
      Amir-Al-Momenin hospital in Rasht were entered the study and divided into two
      equal groups randomly. In both groups anesthesia was induced with propofol,
      remifentanil and cis. atracurium and then, infusion of propofol - remifentanil in
      the first group and isoflurane plus Remifentanil infusion in the second group was
      used for maintenance of anesthesia. Systolic blood pressure was maintained about
      90 mmHg. Then on the basis of maximum allowable blood loss (MABL) formula, we
      calculated the percentage of hemorrhage. Finally the patients' hemorrhage was
      categorized into three groups (< 10%, 10-20%, > 20%). The surgeon's satisfaction
      from surgical field was calculated according to the Visual Analogue Scale. Then
      the data was statistically analyzed with T- test. RESULTS: There were meaningful
      differences between average of hemorrhage (propofol group = 155cc, and Isoflurane
      group = 291.3cc; P = 0.003), and surgeon's satisfaction (propofol group = 1.9 and
      Isoflurane group = 2.95; P = 0.007). CONCLUSIONS: The amount of hemorrhage in
      propofol group was less than Isoflurane group and the field condition was better
      in propofol group than the Isoflurane group.

PMID- 24282775
TI  - Pregnancy outcome using general anesthesia versus spinal anesthesia for in vitro
      fertilization.
AB  - BACKGROUND: There is a considerable rate of fertility failure and this causes a
      great burden of untoward effects for patients. Usually a considerable number of
      these patients undergo anesthesia for their treatment. OBJECTIVES: This study was
      designed to compare the effects of general and spinal anesthesia on these
      patients. PATIENTS AND METHODS: In a randomized clinical trial, after taking
      informed written consent from the patients, 200 patients entered the study; 100
      in each. During a 2 year period, women aged 20 to 40 years entered the study (one
      group receiving spinal anesthesia and the other, receiving general anesthesia).
      Ovum retrieval protocols were the same. Nonparametric and parametric analyses
      were used for data analysis. P value less than 0.05 was considered significant.
      RESULTS: There was no difference between the two groups regarding demographic
      variables. 15 of 100 patients (15%) in the general anesthesia group and 27 of 100
      patients (27%) in the spinal anesthesia group had successful pregnancy after IVF;
      so, spinal anesthesia increased significantly the chance of IVF success (P value
      < 0.001; Chi Square). CONCLUSIONS: The results of this study demonstrated that
      spinal anesthesia increased the chance of fertilization success.

PMID- 24282776
TI  - Post-intubation sore throat and menstruation cycles.
AB  - BACKGROUND: Postoperative sore throat is one of the most common complications of
      general anesthesia and intubation with prevalence of 18%-65% in different
      studies. Several risk factors including female gender, postoperative nausea and
      vomiting and so on have been mentioned. OBJECTIVES: The aim of this study was to
      evaluate the incidence of postoperative sore throat in females and its
      association with menstrual cycles. PATIENTS AND METHODS: One hundred females
      between 18-45 years old with ASA class I or II without predicted difficult airway
      that were candidate for operation in supine position were enrolled in study.
      Patients who had pulmonary disease, smoking, common cold within two weeks prior
      to the operation, previous traumatic intubation history, removable dentures, any
      congenital or acquired deformity in face, neck, mouth and airway, any known
      pathology in mouth like aphthous and mouth ulcer,pregnant women, and patients
      with irregular cycles, and those taking oral contraceptive pills were excluded.
      By the same protocol general anesthesia was provided and the patients were asked
      to fill out a three-point scale questionnaire (Low, High, None) 1,6 and 24 hours
      following intubation to study and record the incidence and severity of sore
      throat, dysphagia and hoarseness. The date of last menstrual period had been
      recorded as well. RESULTS: Of 100 patients, in the first six hours, 51 patients
      had sore throat and 49 had no pain. During the first 6 hours, 33 patients (33%)
      had dysphagia and 13 patients had hoarseness at 6th postoperative hour. Age,
      weight, LMP, intubation time, operation and extubation time and coughing were
      compared to sore throat, dysphagia and hoarseness. The association between the
      incidence of coughing and bucking and sore throat was significant (P = 0.03).
      None of the parameters had a statistically meaningful association with dysphagia.
      CONCLUSIONS: According to our results, by omitting probable risk factors of
      incidence of sore throat and evaluation of role of hormonal changes in women
      represented in menstrual cycles, there was no significant association between
      menstrual cycle and sore throat incidence.

PMID- 24282777
TI  - The Treatment of Joint Pain with Intra-articular Pulsed Radiofrequency.
AB  - BACKGROUND: The intra-articular (IA) application of pulsed radiofrequency (PRF)
      for pain in small and large joints represents a recent development that has
      proven to be effective in many cases. We performed a retrospective study of 89
      such procedures in 57 consecutive patients with chronic articular pain.
      OBJECTIVES: The aim of this retrospective study is to evaluate the effectiveness
      of intraarticular PRF in a group of 57 consecutive patients with chronic joint
      pain. PATIENTS AND METHODS: Patients with intractable joint pain for more than 6
      months were treated with IA PRF 40-45V for 10-15 min in small joints and 60V for
      15 min in large joints using fluoroscopic confirmation of correct needle
      position. A total of 28 shoulders, 40 knees, 10 trapezio-metacarpal, and 11 first
      metatarso-phalangeal joints were treated. Results were evaluated at 1, 2, and 5
      months. The procedure was repeated after 1 month in 10 patients with initial
      suboptimal results. Success was defined as a reduction of pain score by at least
      50%. RESULTS: All groups showed significant reductions in pain scores at all
      three follow-up visits. Success rates were higher in small joints (90% and 82%,
      respectively) than large ones (64% and 60%, respectively). Interestingly, IA PRF
      was successful in 6 out of 10 patients who had undergone previous surgery,
      including 3 with prosthetic joint replacement and in 6 of the 10 repeated
      procedures. There were no significant adverse effects or complications.
      CONCLUSIONS: IA PRF induced significant pain relief of long duration in a
      majority of our patients with joint pain. The exact mechanism is unclear, but may
      be related to the exposure of immune cells to low-strength RF fields, inducing an
      anti-inflammatory effect. The success rate appears to be highest in small joints.
      We recommend additional research including control groups to further investigate
      and clarify this method; our data suggest that it may represent a useful modality
      in the treatment of arthrogenic pain.

PMID- 24282778
TI  - Ultrasound-guided greater occipital nerve blocks and pulsed radiofrequency
      ablation for diagnosis and treatment of occipital neuralgia.
AB  - Occipital neuralgia is a condition manifested by chronic occipital headaches and
      is thought to be caused by irritation or trauma to the greater occipital nerve
      (GON). Treatment for occipital neuralgia includes medications, nerve blocks, and
      pulsed radiofrequency ablation (PRFA). Landmark-guided GON blocks are the
      mainstay in both the diagnosis and treatment of occipital neuralgia. Ultrasound
      is being utilized more and more in the chronic pain clinic to guide needle
      advancement when performing procedures; however, there are no reports of
      ultrasound used to guide a diagnostic block or PRFA of the GON. We report two
      cases in which ultrasound was used to guide diagnostic greater occipital nerve
      blocks and greater occipital nerve pulsed radiofrequency ablation for treatment
      of occipital neuralgia. Two patients with occipital headaches are presented. In
      Case 1, ultrasound was used to guide diagnostic blocks of the greater occipital
      nerves. In Case 2, ultrasound was utilized to guide placement of radiofrequency
      probes for pulsed radiofrequency ablation of the greater occipital nerves. Both
      patients reported immediate, significant pain relief, with continued pain relief
      for several months. Further study is needed to examine any difference in outcomes
      or morbidity between the traditional landmark method versus ultrasound-guided
      blocks and pulsed radiofrequency ablation of the greater occipital nerves. 

PMID- 24282779
TI  - Unusually prolonged motor and sensory block following single injection ultrasound
      guided infraclavicular block with bupivacaine and dexamethasone.
AB  - We present a case of unexpectedly prolonged motor and sensory block following a
      successful single injection ultrasound - guided infraclavicular block with
      bupivacaine (0.25%) and dexamethasone (8 mg). ultrasound guidance and safety
      measurement such as injection of the local anaesthetic at a slow rate and
      verifying that usual resistance was felt throughout the injection, has been
      applied. It took 42 hours for the block to go away. Although there was no
      evidence of neurologic injury but we should always be prepared to consider the
      possibility of nerve injury and take appropriate measures. 

PMID- 24282780
TI  - Regional analgesia in intensive care unit.

PMID- 24282782
TI  - High prevalence of atrial fibrillation among Greenlanders with ischemic stroke -
      atrial fibrillation found in more than 30% of cases.
AB  - OBJECTIVES: To estimate the prevalence of atrial fibrillation among Greenlanders
      with ischemic stroke. STUDY DESIGN: A cross-sectional study. METHODS: Information
      on atrial fibrillation and vitamin K antagonistic treatment at admittance and at
      discharge was obtained for Greenlanders admitted to Queen Ingrid's Hospital in
      Nuuk with an ischemic stroke in 2011 or in 2012 with methods described in details
      elsewhere. RESULTS: Of 139 patients (64 males and 75 females) Greenlanders with
      an ischemic stroke in 2011 (n=74) or 2012 (n=65), 5.0% (n=7) had known atrial
      fibrillation prior to stroke compared to 32.4% (n=45) after discharge (p<0.01).
      CONCLUSIONS: More than 30% of ischemic stroke patients in this study had atrial
      fibrillation and only 5% were diagnosed prior to the stroke, suggesting that
      unknown atrial fibrillation is a substantial risk factor of ischemic stroke among
      Greenlanders.

PMID- 24282783
TI  - Incidence of Greenlandic stroke-survivors in Greenland: a 2-year cross-sectional
      study.
AB  - OBJECTIVES: To estimate age- and gender-specific incidence rates among
      Greenlandic stroke-survivors. STUDY DESIGN: The study was performed as a cross
      sectional observational study. METHODS: All Greenlandic patients admitted to
      Queen Ingrid's Hospital (QIH) with stroke in 2011 and 2012 were included in the
      study. Data were obtained from patient files and the Central Civil Registration
      System. Age- and gender-specific incidence rates were estimated as cases/100,000
      adults/year. Direct age-standardized incidence rate was calculated using the WHO
      2000-2005 population as the standard. RESULTS: In 2011 and 2012, 156 cases of
      stroke were registered, 72 (46.2%) males and 84 (53.8%) females. The overall
      incidence rate of stroke was 155/100,000 person-years (95% CI 121-190), with
      ischemic stroke accounting for 89.1% of these. No significant differences were
      seen between men and women. Direct age-standardized incidence rate was
      149/year/100,000 (95% CI 192-264). Median age at time of diagnosis was 60 years
      (interquartile range 53-69). CONCLUSIONS: This study reports an age-standardized
      all-stroke incidence rate of Greenlandic stroke-survivors in Greenland within the
      wide range as incidences in Western Europe. A noticeable difference when compared
      to Denmark was that male and female incidence were approximately the same, and
      that incidence rates were high in the younger age groups. The majority of strokes
      were of ischemic origin.

PMID- 24282784
TI  - Future human health research directions for the Canadian Northern Contaminants
      Program.
AB  - Studies conducted in the mid-1980s and early 1990s demonstrated that persistent
      organic pollutants (POPs) and metals were reaching the Arctic ecosystem at
      unexpectedly high levels, many of which had no Arctic or Canadian sources.
      Epidemiological and toxicological studies in Canada and in other countries have
      found that these contaminants may pose a risk to human health. The objective of
      this paper is to provide the foundation for the discussion on future northern
      human health research under the Northern Contaminants Program (NCP) in Canada.
      This short discussion of human health priorities will help guide a path forward
      for future northern human health research in Canada to address on-going and new
      health concerns related to contaminants exposure in the Canadian Arctic. 

PMID- 24282785
TI  - Which Sami? Sami inclusion criteria in population-based studies of Sami health
      and living conditions in Norway - an exploratory study exemplified with data from
      the SAMINOR study.
AB  - BACKGROUND: In a situation where national censuses do not record information on
      ethnicity, studies of the indigenous Sami people's health and living conditions
      tend to use varying Sami inclusion criteria and categorizations. Consequently,
      the basis on which Sami study participants are included and categorized when Sami
      health and living conditions are explored and compared differs. This may
      influence the results and conclusions drawn. OBJECTIVE: To explore some numerical
      consequences of applying principles derived from Norway's Sami Act as a
      foundation for formalized inclusion criteria in population-based Sami studies in
      Norway. DESIGN: We established 1 geographically based (G1) and 3 individual-based
      Sami example populations (I1-I3) by applying diverse Sami inclusion criteria to
      data from 17 rural municipalities in Norway north of the Arctic Circle. The data
      were collected for a population-based study of health and living conditions in
      2003-2004 (the SAMINOR study). Our sample consisted of 14,797 participants aged
      36-79 years. RESULTS: The size of the individual-based populations varied
      significantly. I1 (linguistic connection Sami) made up 35.5% of the sample, I2
      (self-identified Sami) made up 21.0% and I3 (active language Sami) 17.7%. They
      were also noticeably unevenly distributed between the 5 Sami regions defined for
      this study. The differences for the other characteristics studied were more
      ambiguous. For the population G1 (residents in the Sami language area) the only
      significant difference found between the Sami and the corresponding non-Sami
      population was for household income (OR=0.69, 95% CI: 0.63-0.74). For the
      populations I1-I3 there were significant differences on all measures except for
      I2 and education (OR=1.09, 95% CI: 0.99-1.21). CONCLUSIONS: The choice of Sami
      inclusion criterion had a clear impact on the size and geographical distribution
      of the defined populations but lesser influence on the selected characteristics
      for the Sami populations relative to the respective non-Sami ones.

PMID- 24282786
TI  - MicroRNA and Renal Allograft Monitoring.

PMID- 24282787
TI  - Diverse clinical and histology presentation in c1q nephropathy.
AB  - Patients presenting with nephrotic syndrome with or without nephritic illness
      rarely come across with the diagnosis of 'C1q nephropathy'. This entity is purely
      diagnosed with the help of immunofluorescence like IgA nephropathy. Clinical
      presentation is heterogenous, ranging from nephrotic range proteinuria to sub
      nephrotic state; and with or without hematuria / renal insufficiency. Similarly,
      the concept of 'C1q nephroapthy' has periodically evolved since its original
      description by Jenette and Hipp in 1985. Here the pathophysiology, histologic
      findings / diagnostic and therapeutic options in patients with C1q nephropathy
      are discussed. 

PMID- 24282781
TI  - Centrosome dysfunction contributes to chromosome instability, chromoanagenesis,
      and genome reprograming in cancer.
AB  - The unique ability of centrosomes to nucleate and organize microtubules makes
      them unrivaled conductors of important interphase processes, such as
      intracellular payload traffic, cell polarity, cell locomotion, and organization
      of the immunologic synapse. But it is in mitosis that centrosomes loom large, for
      they orchestrate, with clockmaker's precision, the assembly and functioning of
      the mitotic spindle, ensuring the equal partitioning of the replicated genome
      into daughter cells. Centrosome dysfunction is inextricably linked to aneuploidy
      and chromosome instability, both hallmarks of cancer cells. Several aspects of
      centrosome function in normal and cancer cells have been molecularly
      characterized during the last two decades, greatly enhancing our mechanistic
      understanding of this tiny organelle. Whether centrosome defects alone can cause
      cancer, remains unanswered. Until recently, the aggregate of the evidence had
      suggested that centrosome dysfunction, by deregulating the fidelity of chromosome
      segregation, promotes and accelerates the characteristic Darwinian evolution of
      the cancer genome enabled by increased mutational load and/or decreased DNA
      repair. Very recent experimental work has shown that missegregated chromosomes
      resulting from centrosome dysfunction may experience extensive DNA damage,
      suggesting additional dimensions to the role of centrosomes in cancer. Centrosome
      dysfunction is particularly prevalent in tumors in which the genome has undergone
      extensive structural rearrangements and chromosome domain reshuffling. Ongoing
      gene reshuffling reprograms the genome for continuous growth, survival, and
      evasion of the immune system. Manipulation of molecular networks controlling
      centrosome function may soon become a viable target for specific therapeutic
      intervention in cancer, particularly since normal cells, which lack centrosome
      alterations, may be spared the toxicity of such therapies. 

PMID- 24282789
TI  - Yang-Monti's Catheterizable Stoma in Children.
AB  - BACKGROUND: In 1981, Mitrofanoff described a procedure to create a continent
      urinary stoma for clean intermittent catheterization. Since then several
      procedures have been described including Yang-Monti ileovesicostomy for effective
      catheterization. OBJECTIVES: We report on our experience from the use of Monti's
      procedure in children at our center. PATIENTS AND METHODS: Children < 18 years of
      age undergoing urinary diversion/reconstruction with Yang-Monti's procedure for
      congenital conditions or neuropathic bladder formed the study group. All these
      children, post-operatively were taught clean intermittent catheterization (CIC)
      and put on a regime using a 14/16 Fr catheter every 3 hours. The children were
      followed regularly at 3, 6, 12, 18 and 24months post-operatively, with special
      attention paid to any problems with catheterization and incontinence. RESULTS:
      During the period from Jan 2000 to Dec 2011, at our center, 19 children less than
      eighteen years of age underwent urinary diversion with Yang-Monti's
      catheterizable stoma. The indications for urinary diversion was neuropathic
      bladder in eight, exstrophy bladder in seven , valve bladder syndrome in three
      and persistent urethral stricture in one. None of the children found CIC
      difficult during the post-operative period and there was no hindrance to the
      passage of the catheter. CONCLUSIONS: Although the appendix remains the tissue of
      choice for creation of catherterizable stoma, the Yang-Monti ileovesicostomy is
      effective, convenient conduit for children. Long-term complications are minimal
      and children find this comfortable to do CIC.

PMID- 24282790
TI  - The relationship between erythropoietin resistance and antibody response to
      hepatitis B vaccine in hemodialysis patients.
AB  - BACKGROUND: Seroconversion following Hepatitis B virus (HBV) vaccine in
      hemodialysis (HD) patients has been shown to be suboptimal. Nutritional and
      immunological factors were shown to influence the seroconversion related to HBV
      vaccination in HD patients. Resistance to erythropoiesis stimulating agents (ESA)
      for correction of anemia has also been shown to be associated with nutrition and
      inflammation in these patients. OBJECTIVES: The aim of the current study was to
      analyze the relationship between anti-HBs response and erythropoietin (EPO)
      resistance in HD patients. PATIENTS AND METHODS: Demographics, clinical
      characteristics, laboratory parameters and the data about vaccination status were
      obtained from dialysis charts and vaccination registries retrospectively. To
      calculate the EPO resistance ESA hypo responsiveness index (EHRI) was used. The
      EHRI was calculated through deviding the weekly dose of EPO by per kilogram of
      body weight divided by the hemoglobin level. Patients were divided into non
      seroconversion (anti-HBs titers were < 10 IU/L) and seroconversion groups (anti
      HBs titers were >= 10 IU/L) after completion of the four-dose vaccination
      schedule. RESULTS: In total 97 patients were enrolled. For the entire group,
      stepwise linear regression analysis revealed that square root transformed anti
      HBs levels were independently associated with age (P = 0.016), blood urea
      nitrogen (P = 0.019), high sensitive C-Reactive Protein (P = 0.009), and square
      root transformed EHRI (P = 0.019). Logistic regression analysis have also
      demonstrated that blood urea nitrogen (P = 0.002), creatinine (P = 0.046),
      albumin (P = 0.01) and square root transformed EHRI (P = 0.011) were
      independently related to seroconversion. CONCLUSIONS: EPO resistance was
      negatively associated with anti-HBs levels and seroconversion. More studies are
      needed to highlight the underlying mechanisms regarding EPO resistance and
      response to HBV vaccination in HD patients.

PMID- 24282788
TI  - Molecular pathways in prostate cancer.
AB  - OBJECTIVES: Prostate cancer is a prevalent disease with a high impact on
      patients' morbidity and mortality. Despite efforts to profile prostate cancer,
      the genetic alterations and biological processes that correlate with disease
      progression remain partially elusive. The purpose of this study is to review the
      recent evidence relating to the initiation and progression of prostate cancer in
      relation to the familial correlation of the disease, the genetic aberrations
      resulting in prostate cancer and the new molecular biology data regarding
      prostate cancer. MATERIALS AND METHODS: A Medline database search identified all
      the existing publications on the molecular events associated with the
      pathogenesis and evolution of prostate cancer. Particular emphasis was given on
      the specific genetic phenomena associated with prostate cancer. RESULTS: Like
      other cancers, prostate cancer is caused by an accumulation of genetic
      alterations in a cell that drives it to malignant growth. Specific genes and gene
      alterations have been suggested to play a role in its development and
      progression. Aneuploidy, loss of heterozygosity, gene mutations, hypermethylation
      and inactivation of specific tumour suppressor genes such as GSTpi, APC, MDR1,
      GPX3 and others have been detected in prostate cancers, but generally only at a
      low or moderate frequency. The androgen receptor (AR) signalling pathway may play
      a crucial role in the early development of prostate cancer, as well as in the
      development of androgen-independent disease that fails to respond to hormone
      deprivation therapies. Other alterations linked to the transition to hormone
      independence include amplification of MYC and increased expression of ERBB2 and
      BCL2. Inflammatory changes may also contribute to the development of prostate
      cancer. CONCLUSION: The identification of specific molecular markers for prostate
      cancer may lead to its earliest detection and better prediction of its behavior.
      The better understanding of the molecular events affecting prostate cancer
      progression may result in the introduction of new drugs to target these events
      thus providing a potential cure and a tool for prevention of this very common
      disease.

PMID- 24282791
TI  - Role of the ACE ID and PPARG P12A Polymorphisms in Genetic Susceptibility of
      Diabetic Nephropathy in a South Indian Population.
AB  - BACKGROUND: Diabetic nephropathy (DN) is one of the life-threatening disorders
      characterized by persistent albuminuria, raised arterial blood pressure, a
      lowered glomerular filtration rate, and high risk of cardiovascular morbidity and
      mortality. The vascular genes ACE (Angiotensin-converting enzyme), and PPARG
      (peroxisome proliferator activated receptor gamma) are involved in alterations in
      vascular endothelium, and are suggested to play a role in the susceptibility of
      diabetic nephropathy. OBJECTIVES: The aim of our study was to find out the role
      of ACE ID and PPARG P12A polymorphisms in genetic susceptibility of diabetic
      nephropathy in south Indian population. PATIENTS AND METHODS: A total of 54 cases
      with diabetic nephropathy and 67 control subjects with diabetes were enrolled for
      our study. DNA was isolated from peripheral blood leucocytes, and genotyped using
      PCR-electrophoresis (ACE ID) or PCR-RFLP (PPARG P12A) methods. RESULTS: ACE ID
      genotypes followed Hardy-Weinberg equilibrium in both cases and controls. But
      P12A genotypes deviated from Hardy-Weinberg equilibrium in diabetic controls.
      Chi(2) test was applied for the analysis of genotypic distributions in genotypic
      and dominant models. Odds ratios were also calculated. No significant differences
      in genotype frequencies of ACE ID and PPARG P12A polymorphisms were found on
      comparing patients with diabetic nephropathy with diabetic controls. The
      synergistic role of ACE ID* PPARG P12A interaction, did not show any association
      in patients with diabetic nephropathy when compared to diabetic controls.
      CONCLUSIONS: In conclusion, the ACE and PPARG genes do not have a key role in
      conferring risk for diabetic nephropathy.

PMID- 24282792
TI  - Gender difference in Cisplatin-induced nephrotoxicity in a rat model: greater
      intensity of damage in male than female.
AB  - BACKGROUND: Nephrotoxicity and hepatotoxicity are side effects of Cisplatin (CP)
      therapy. OBJECTIVES: We investigated the role of gender in CP-induced
      nephrotoxicity and hepatotoxicity. MATERIALS AND METHODS: Low dose of CP (1
      mg/kg/day; ip) was administered daily to male and female Wistar rats for 15
      consecutive days. Serum creatinine (Cr), blood urea nitrogen (BUN),
      malondialdehyde (MDA), nitric oxide (NO) metabolite, and magnesium (Mg) levels
      were determined. RESULTS: The percentage of weight loss and the serum levels of
      MDA and nitrite in male and female animals were not statistically different.
      However, the serum levels of BUN, Cr, Mg, and kidney MDA levels, and kidney
      weight and damage score were significantly greater in males than in females (P <
      0.05). CONCLUSIONS: CP-induced nephrotoxicity is gender related for which the
      mechanisms should be determined.

PMID- 24282793
TI  - Effectiveness of omega-3 supplement on lipid profile and lipid peroxidation in
      kidney allograft recipients.
AB  - BACKGROUND: Omega-3 fatty acids carry major roles in mediating inflammation,
      immune response, lipid peroxidation and lipoprotein metabolism. Diversity of
      health benefits have been attributed to dietary supplementation with omega-3
      fatty acids in transplant and nontransplant settings. Several studies in renal
      transplantation have suggested that supplementation with omega-3 fatty acids may
      lead to significant clinical benefits. However, the extents of these benefits are
      variable and published data had not coincided with positive findings. OBJECTIVES:
      The aim of this study was to evaluate the effectiveness of omega-3
      supplementation on the lipid profile and lipid peroxidation in patients underwent
      kidney transplant. PATIENTS AND METHODS: Thirty cases had been selected with
      stable allograft function following at least six months of transplantation. The
      serum levels of lipids including triglyceride, low density lipoprotein (LDL),
      high density lipoprotein (HDL), very low density lipoprotein (VLDL), total
      cholesterol and indices of lipid peroxidation (malondialdehyde and APO a1) were
      measured by biochemical techniques at the baseline. Two months following
      prescription of oral omega-3 (3 g/day), the biochemical measurements were
      repeated and the differences were analyzed. RESULTS: Of thirty patients, 12 were
      male and 18 were female with the mean age of 45.3 +/- 13.0 (18-65) years. At the
      baseline, the serum levels of MDA and APO B were 3.5 +/- 1.3 and 148.3 +/- 20.4
      ng/dL respectively. At the end of two months following intervention, they were
      3.2 +/- 1.2 and 145.7 +/- 19.0 ng/dL, respectively (P > 0.05). Correspondingly,
      at the baseline the serum levels of triglyceride, LDL, VLDL and total cholesterol
      were 171.1 +/- 58.7, 106.9 +/- 31.8, 42.2 +/- 4.0, 145.7 +/- 33.2 and 181.2 +/-
      35.1 mg/dL and after intervention they were 162.4 +/- 82.5, 99.4 +/- 35.1, 44.6
      +/- 6.3, 140.3 +/- 33.1 and 170.9 +/- 38.3 mg/dL, respectively (P > 0.05). There
      was no significant difference between the males and females in this instance.
      CONCLUSIONS: Our results seem to indicate that oral omega-3 may promote the lipid
      profile and indices of lipid peroxidation in patients following kidney
      transplantation however extents of these effects are not significant.

PMID- 24282794
TI  - Comparison of efficacy of side to side versus end to side arteriovenous fistulae
      formation in chronic renal failure as a permanent hemodialysis access.
AB  - BACKGROUND: In candidate patients for permanent hemodialysis or dialysis on a
      regular basis, an appropriate vascular access has great importance. The best
      permanent access is AVF (arterio venous fistula). Use of a technique to create
      AVF with better patency seems to be logical. OBJECTIVES: The present study aimed
      to compare the efficacy rate of AVFs using two different anastomosis methods;
      Side to Side (STS) versus End to Side (ETS) and to determine whether the
      different approaches render any preferences or complications. PATIENTS AND
      METHODS: Sixty end stage renal disease (ESRD) patients were included in this
      clinical trial in two assigned groups of 30 patients. In one group end to side
      method to create AVF was used while in the other group Side to Side technique was
      applied for access in surgery. Both groups were followed for duration of 6 months
      to assess patency. For evaluating the quantitive variables, t-test was used while
      qualitative variables were measured using the chi-square and Fisher's exact
      tests. RESULTS: In the 6 months duration, 6 patients (20%) in the STS (side to
      side) group and 5 patients (16.6%) in the ETS (end to side) group experienced a
      non-functional AVF. In the ETS group the failure was generally a result of
      thrombosed access while in the STS group, 4 out of 6 patients with complications,
      experienced thrombosis while the other 2 patients had venous hypertension. The
      total failure rate was 18.3% and during the 6 months of follow up no significant
      difference was detected in the efficacy rate. Nevertheless, in case of longer
      follow ups, different outcomes could be seen. CONCLUSIONS: This study
      demonstrated that there was no significant statistical difference between the
      functional patency rates of fistulae placed by STS or ETS methods.

PMID- 24282795
TI  - Dyslipidemia after kidney transplantation and correlation with cyclosporine
      level.
AB  - BACKGROUND: Dyslipidemia after kidney transplantation is a frequent finding and
      is multifactorial. Immunosuppressive agents such as cyclosporine (CsA) can cause
      hypercholesterolemia. OBJECTIVES: As there were few reports with conflicting
      evidence on whether CsA related dyslipidemia is dose related and that CsA
      monitoring assays (trough level, C0, or two hour post dose level, C2) is a better
      predictor for dyslipidemia development; hence, the current study, in a large
      sample size, was designed to answer these questions. PATIENTS AND METHODS: In the
      current retrospective cross sectional study, 1391 kidney transplant recipients
      were enrolled. All patients received CsA plus mycophenolatemofetile or
      azathioprine and prednisolone. Serum creatinine, CsA blood levels and lipid
      profile were measured after 12-14 h fasting. Mann-Whitney and Kruskal-Wallis,
      Pearson's test and logistic regression were used for data analyses. RESULTS: Mean
      age of 1391studied population was 38.7 +/- 15 years old. Hypercholesterolemia and
      hypertriglyceridemia were observed in 58.9% and 86.6%, respectively and they were
      more significantly detected in cadaveric kidney transplantation. Dyslipidemia had
      weak correlation with age of recipient, serum creatinine, C0 and C2 levels of
      CsA. At logistic regression, serum creatinine was the only risk factor for
      hypercholesterolemia development after kidney transplantation (OR = 1.6, CI 95%:
      1.4 -1.8). CONCLUSIONS: Dyslipidemia is a common finding after kidney
      transplantation and has no correlation with CsA level. According to conflicting
      data on the precise effect of different factors in inducing dyslipidemia,
      prospective large sample size studies should consider better control of
      dyslipidemia.

PMID- 24282796
TI  - Does living donor hyperoxia have an impact on kidney graft function after
      transplantation?
AB  - BACKGROUND: Improvement in the outcome of organ transplantation is related to
      advances in patient selection criteria, organ preservation, operative techniques,
      perioperative care and efficacy of immunosuppressive agents. OBJECTIVES: We aimed
      to evaluate the effects of higher levels of arterial PaO2 in donors on DGF
      (delayed graft function). PATIENTS AND METHODS: Forty patients over 18 years old
      with stage 4-5 chronic kidney disease (CKD) who received a kidney from living
      donors were enrolled. They were randomly grouped in to the case (n = 17) and
      control (n = 23) groups and were followed for 2 weeks after transplantation.
      Donors were exposed to 60% oxygen for at least 2 hours with a face-mask (venture
      mask) for 2 consecutive days before transplantation until arterial oxygen
      pressure increased in arterial blood gas to 200 mmHg. Neutrophil gelatinase
      associated lipocalin (NGAL), Interleuk-18 (IL-18), tumor necrosis factor- alpha
      (TNF-alpha) and transforming growth factor-beta (TGF-beta) could be good
      biomarkers for early diagnosis of kidney injury in renal transplant recipients;
      we assessed kidney function with these biomarkers. RESULTS: Forty living kidney
      transplantations including 17 cases and 23 controls were performed; female gender
      was more prevalent in recipients (n = 16, 40%). The mean age of recipients was
      36.1 +/- 12.4 (18-67) years old. DGF was detected in 2 (5.95%) individuals, from
      whom one was in the case group and the other one in the control group. In the
      univariate analysis, there was no significant correlation between age and
      biomarkers in urine and serum unless for the second serum NGAL (P = 0.02, r = 
      0.06) and second urine IL 18 (P = 0.03, r = -0.5) which had a negative
      correlation, and first urine TNF alpha (P = 0.02, r = 0.7) which had a positive
      correlation. CONCLUSIONS: Oxygen therapy in the case group had no significant
      impact on protection from DGF.

PMID- 24282797
TI  - Primary Non-Hodgkin's Lymphoma of Penis Masquerading as a Non-Healing Ulcer in
      the Penile Shaft.
AB  - Primary malignant lymphoma of the male external genitalia is extremely rare and
      it is even rarer in the penis. Because of its rarity, the possibility of delay in
      diagnosis and mismanagement is always there. It can present as a nodule, non
      healing ulcer, stricture urethra or periurethral abscess. We report a case
      presenting first a nodule and later on as a non-healing ulcer which was diagnosed
      by corporal biopsy and managed successfully with chemotherapy. 

PMID- 24282798
TI  - Vanished kidney by pheripheral nerve seath tumor: a rare case report.
AB  - Malignant peripheral nerve-sheath tumor (MPNST) is a high-grade malignant tumor
      of ecto-mesenchymal origin comprising approximately 10% of soft-tissue sarcomas.
      They tend to occur associated with neurofibromatosis or sporadically. Here we
      report a MPNST at an extremely rare location and behavior causing disappearance
      of the entire kidney. Patient evaluation included clinical, biochemical and
      radiological studies before treatment. Histological study revealed the rare
      diagnosis. Patient was asymptomatic at six-month follow-up after treatment. 

PMID- 24282799
TI  - Combined percutaneous and transurethral lithotripsy for forgotten ureteral stents
      with giant encrustation.

PMID- 24282800
TI  - Renal bone disease among patients with ESRD.

PMID- 24282801
TI  - Health-related quality of life in kidney transplant recipients.

PMID- 24282802
TI  - Prevalence of renal osteodystrophy in african hemodialysis patients.

PMID- 24282803
TI  - New horizon for the therapeutic modality of exercise on neuropsychiatric
      disorders.

PMID- 24282804
TI  - Treadmill exercise alleviates prenatal noise stress-induced impairment of spatial
      learning ability through enhancing hippocampal neurogenesis in rat pups.
AB  - Stress alters brain cell properties and then disturbs cognitive processes, such
      as learning and memory. In this study, we investigated the effect of postnatal
      treadmill exercise on hippocampal neurogenesis and spatial learning ability of
      rat pups following prenatal noise stress. The impact of exercise intensity (mild
      intensity exercise vs heavy-intensity exercise) was also compared. The pregnant
      rats in the stress-applied group were exposed to a 95 dB supersonic machine sound
      for 1 h once a day from the 15th day after mating until delivery. After birth,
      the rat pups in the exercise groups were made to run on a treadmill for 30 min
      once a day for 7 consecutive days, starting 4 weeks after birth. The spatial
      learning ability was tested using radial-arm maze task and hippocampal
      neurogenesis was determined by 5-bromo-2'-deoxyuridine (BrdU)
      immunohistochemistry. The rat pups born from the stress-applied maternal rats
      spent more time for the seeking of water and showed higher number of error in the
      radial-arm maze task compared to the control group. These rat pups showed
      suppressed neurogenesis in the hippocampus. In contrast, the rat pups performed
      postnatal treadmill exercise saved time for seeking of water and showed lower
      number of error compared to the stress-applied group. Postnatal treadmill
      exercise also enhanced neurogenesis in the hippocampus. The mild-intensity
      exercise showed more potent impact compared to the heavy-intensity exercise. The
      present results reveal that postnatal treadmill exercise lessens prenatal stress
      induced deterioration of brain function in offspring. 

PMID- 24282805
TI  - Short-term treadmill exercise preserves sensory-motor function through inhibiting
      apoptosis in the hippocampus of hypoxic ischemia injury rat pups.
AB  - Perinatal hypoxic ischemia injury is a common cause of morbidity and mortality in
      neonates. Physical exercise may ameliorate neurological impairment by impeding
      neuronal loss following various brain insults. In the present study, the effect
      of treadmill exercise on sensory-motor function in relation with hippocampal
      apoptosis following hypoxic ischemia brain injury was investigated. Sensory-motor
      function was determined by walking initiation test and apoptosis was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining and caspase-3 immunohistochemistry. On postnatal 7 day, left common
      carotid artery of the neonatal rats was ligated for two hours and then the
      neonatal rats were exposed to hypoxia conditions for one hour. The rat pups in
      the exercise groups were forced to run on a motorized treadmill for 30 min once a
      day for 10 days, starting 22 days after induction of hypoxic ischemia brain
      injury. Hypoxic ischemia caused sensory-motor disturbance with enhancement of
      apoptosis in the hippocampus. Short-term treadmill exercise suppressed hypoxic
      ischemia injury-induced apoptosis in the hippocampus, and preserved sensory-motor
      function of hypoxic ischemia injury rat pups. 

PMID- 24282806
TI  - The impact of duration of one bout treadmill exercise on cell proliferation and
      central fatigue in rats.
AB  - The purpose of this study was to investigate the impact of the duration
      dependence of the one bout treadmill exercise on cell proliferation, stress, and
      central fatigue in rats. The animals were randomly divided into five groups: the
      non-exercise group, 1-h exercise group, 2-h exercise group, 4-h exercise group,
      and 6-h exercise group. The exercise load consisted of running at speed of 13
      meters/min with the 0 degrees  inclination. Cell proliferation in the hippocampal
      dentate gyrus was increased in response to one bout moderate treadmill exercise
      in all exercise groups. But there was no statistical significance between the
      exercise duration and cell proliferation. The optical density of glucocorticoid
      (GR)-positive cells in the hippocampal dentate gyrus was not changed by treadmill
      exercise at any exercise duration. Expressions of serotonin (5-hydroxytryptamine,
      5-HT) and tryptophan hyroxylase (TPH) were increased by treadmill exercise only
      at 6 h duration. It seemed like that there was no additional benefits on cell
      proliferation over 2 h exercise due to stressful factors with over exercise dose,
      and there was no change of GR expression due to early assessment point of time.
      It can be suggested that the one-bout of moderate treadmill exercise increased
      cell proliferation, but treadmill exercise prolonged to 6 h induced central
      fatigue in rats. 

PMID- 24282807
TI  - Diabetes reduces the cognitive function with the decrease of the visual
      perception and visual motor integration in male older adults.
AB  - This study investigated the influence of diabetes on cognitive decline between
      the diabetes and non- diabetes patients and identified the associations between
      diabetes and cognitive function, visual perception (VP), and visual motor
      integration (VMI). Sixty elderly men (67.10+/- 1.65 yr) with and without diabetes
      (n= 30 in each group) who were surveyed by interview and questionnaire in South
      Korea were enrolled in this study. The score of Mini-Mental State Examination of
      Korean version (MMSE-KC), Motor-free Visual Perception Test-Vertical Format (MVPT
      V), and Visual-Motor Integration 3rd Revision (VMI-3R) were assessed in all of
      the participants to evaluate cognitive function, VP, and VMI in each. The score
      of MMSE-KC in the diabetic group was significantly lower than that of the non
      diabetes group (P< 0.01). Participants in the diabetes group also had lower MVPT
      V and VMI-3R scores than those in the non-diabetes group (P< 0.01, respectively).
      Especially, the scores of figure-ground and visual memory among the subcategories
      of MVPT-V were significantly lower in the diabetes group than in the non-diabetes
      group (P< 0.01). These findings indicate that the decline in cognitive function
      in individuals with diabetes may be greater than that in non-diabetics. In
      addition, the cognitive decline in older adults with diabetes might be associated
      with the decrease of VP and VMI. In conclusion, we propose that VP and VMI will
      be helpful to monitor the change of cognitive function in older adults with
      diabetes as part of the routine management of diabetes-induced cognitive
      declines. 

PMID- 24282808
TI  - Objective control skills among students with intellectual disability at special
      school in Korea.
AB  - The purpose of this study was to examine the level of objective control skill and
      performance criteria of students with intellectual disability at special school.
      Three hundred thirty one students with intellectual disability were participated
      this study (M: 230, F: 101). Their aged was from 10-18 aged old. We had the test
      the objective control skill by video, objective control skill consisted of
      overhand throwing, catching, kicking, hitting, dribbling. Data were analyzed
      using liner regression and calculated mean, standard error, standard deviation
      and 95% confidence interval. Total objective control skill mastery was 47%, and
      hitting skill score was the highest than another subtest, the lowest performance
      skill was overhand throwing. There were showed that not significant difference
      object control skill in according to gender. Also not effect object control skill
      and subtest in according to age except dribbling. It was showed that significant
      effect objective control skill in according to disability level. 

PMID- 24282809
TI  - Effects of peripheral injury in athletes with long-term-exercise participation in
      modern pentathlons.
AB  - This study was conducted to verify the effect of the ankle injury of athletes who
      attended the modern pentathlon for a long-term basis on ankle muscle's strength
      and proprioceptive sensory function. For this, 10 athletes of the modern
      pentathlon, with experience of having damaged one side of their ankles within 6
      months, and 10 healthy male college students, who have similar personal
      characteristics, such as height, age, and weight and have no experience of
      participating in regular sports for 3 or more times a week. The experimental
      subject was divided into 3 groups in all. After the flexor power of the plantar
      and dorsal side and the muscle strength of the varus and valgus for an ankle were
      measured by the Biodex System III at an angular velocity of 60 degrees /sec and
      120 degrees /sec, it was documented as the maximum couple of force per body
      weight. Also, specified receptive senses were measured by the Biodex System III
      using the stop button to find the position (angle) of the joint. As a result of
      the conclusive research, participation in modern pentathlons for a long-term
      basis has caused an increase in valgus muscle strength and flexor power of the
      plantar side of the ankle when compared to general college students. Sports
      related injury of the ankle was also found to result into the weakening of the
      flexor power on the plantar side and valgus muscle strength and a decrease of the
      proprioceptive sensory function. 

PMID- 24282810
TI  - Clinical usefulness of the virtual reality-based postural control training on the
      gait ability in patients with stroke.
AB  - This study is a single blind randomized controlled trial to determine the effect
      of virtual reality-based postural control training on the gait ability in
      patients with chronic stroke. Sixteen subjects were randomly assigned to either
      experimental group (VR, n= 8) or control group (CPT, n= 8). Subjects in both
      groups received conventional physical therapy for 60 min per day, five days per
      week during a period of four weeks. Subjects in the VR group received additional
      augmented reality-based training for 30 min per day, three days per week during a
      period of four weeks. The subjects were evaluated one week before and after
      participating in a four week training and follow-up at one month post-training.
      Data derived from the gait analyses included spatiotemporal gait parameters, 10
      meters walking test (10 mWT). In the gait parameters, subjects in the VR group
      showed significant improvement, except for cadence at post-training and follow-up
      within the experimental group. However, no obvious significant improvement was
      observed within the control group. In between group comparisons, the experimental
      group (VR group) showed significantly greater improvement only in stride length
      compared with the control group (P< 0.05), however, no significant difference was
      observed in other gait parameters. In conclusion, we demonstrate significant
      improvement in gait ability in chronic stroke patients who received virtual
      reality based postural control training. These findings suggest that virtual
      reality (VR) postural control training using real-time information may be a
      useful approach for enhancement of gait ability in patients with chronic stroke. 

PMID- 24282811
TI  - A flow cytometric analysis of vitreous inflammatory cells in patients with
      proliferative diabetic retinopathy.
AB  - The purpose of this study was to investigate inflammatory cells in vitreous from
      patients with proliferative diabetic retinopathy (PDR) using flow cytometric
      analysis. Twenty-eight patients with PDR requiring vitrectomy because of macular
      traction or tractional retinal detachment were enrolled in the study (n = 28),
      and 6 patients with macular hole (MH) formed the control group. Samples of
      vitreous and peripheral venous blood were obtained at the beginning of
      vitrectomy. T lymphocytes were found in vitreous from patients with PDR, and
      CD4/CD8 ratio was higher in vitreous (median 4.3) compared to blood (median 1.9;
      P = 0.003). No B lymphocytes were detected in vitreous. The percentage of
      histiocytes/macrophages was significantly higher in vitreous (median 62.1) in
      comparison with blood (median 5.5; P < 0.0001). No lymphocytes were detected in
      vitreous of the control group. There were more T lymphocytes in vitreous from
      patients with active PDR. No association between cells in the vitreous and visual
      acuity improvement after surgery was found. In conclusion, T lymphocytes are
      found in vitreous from patients with PDR and reflect the activity of PDR but do
      not seem to predict visual prognosis. Higher CD4/CD8 ratio in vitreous compared
      to blood from patients with PDR is consistent with local inflammatory response in
      PDR. 

PMID- 24282812
TI  - Defects in base excision repair sensitize cells to manganese in S. cerevisiae.
AB  - Manganese (Mn) is essential for normal physiologic functioning; therefore,
      deficiencies and excess intake of manganese can result in disease. In humans,
      prolonged exposure to manganese causes neurotoxicity characterized by Parkinson
      like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the
      generation of reactive oxygen species. In a recent publication, we showed that Mn
      induced oxidative DNA damage and caused lesions in thymines. This study further
      investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage
      using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those
      defective in base excision repair, glutathione synthesis, and superoxide
      dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of
      mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1
      mutants indicates that exposure to Mn results in accumulation of base
      substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as
      well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and
      Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires
      base excision repair for processing and that Mn interferes with polymerase
      fidelity. The status of base excision repair may provide a biomarker for the
      sensitivity of individuals to manganese. 

PMID- 24282813
TI  - Characterization of the phytochemical constituents of Taif rose and its
      antioxidant and anticancer activities.
AB  - Ward Taifi (Taif rose) is considered one of the most important economic products
      of Taif, Saudi Arabia. In this study both fresh and dry Taif rose were
      biologically and phytochemically investigated. The 80% methanol extracts and n
      butanol fractions of dry and fresh Taif rose had high radical scavenging activity
      toward artificial 1,1-diphenyl picrylhydrazyl (DPPH)(*) radical with SC50 values
      range 5.86-12.24 ug/ml whereas the aqueous fractions showed weak activity. All
      samples had in vitro anticancer activity toward HepG2 with IC50 < 20 ug/ml which
      fall within the criteria of the American Cancer Institute. High positive
      correlation appeared between the antioxidant activity and total phenolics whereas
      there is no correlation between total phenolics and anticancer activity. The LC
      ESI(- ve)-MS analysis of all extracts indicate the presence of phenolic compounds
      belonging to hydrolysable tannins and flavonol glycosides. In conclusion, the
      presence of this is considered to be the first phytochemical report that
      identifies the major compounds in dry and fresh roses using HPLC-ESI-MS. The
      methanol extracts and its n-butanol and aqueous fractions for both fresh and dry
      Taif rose could be used as preventive and therapeutic effective natural agents
      for diseases in which free radicals involved after more in vitro and in vivo
      studies.

PMID- 24282814
TI  - Isolation, characterization, and transplantation of cardiac endothelial cells.
AB  - Isolation and ex vivo expansion of cardiac endothelial cells have been a
      recurrent challenge due to difficulties in isolation, cell heterogeneity, lack of
      specific markers to identify myocardial endothelial cells, and inadequate
      conditions to maintain long-term cultures. Herein, we developed a method for
      isolation, characterization, and expansion of cardiac endothelial cells
      applicable to study endothelial cell biology and clinical applications such as
      neoangiogenesis. First, we dissociated the cells from murine heart by mechanical
      disaggregation and enzymatic digestion. Then, we used flow cytometry coupled with
      specific markers to isolate endothelial cells from murine hearts. CD45+ cells
      were gated out to eliminate the hematopoietic cells. CD31+/Sca-1+ cells were
      isolated as endothelial cells. Cells isolated from atrium grew faster than those
      from ventricle. Cardiac endothelial cells maintain endothelial cell function such
      as vascular tube formation and acetylated-LDL uptake in vitro. Finally, cardiac
      endothelial cells formed microvessels in dorsal matrigel plug and engrafted in
      cardiac microvessels following intravenous and intra-arterial injections. In
      conclusion, our multicolor flow cytometry method is an effective method to
      analyze and purify endothelial cells from murine heart, which in turn can be ex
      vivo expanded to study the biology of endothelial cells or for clinical
      applications such as therapeutic angiogenesis. 

PMID- 24282815
TI  - Measuring activity levels at an acute stroke ward: comparing observations to a
      device.
AB  - BACKGROUND: If a simple system of instrumented monitoring was possible early
      after stroke, therapists may be able to more readily gather information about
      activity and monitor progress over time. Our aim was to establish whether a
      device containing a dual-axis accelerometer provides similar information to
      behavioural mapping on physical activity patterns early after stroke. METHODS:
      Twenty participants with recent stroke <= 2 weeks and aged >18 were recruited and
      monitored at an acute stroke ward. The monitoring device (attached to the
      unaffected leg) and behavioural mapping (observation) were simultaneously applied
      from 8 a.m. to 5 p.m. Both methods recorded the time participants spent lying,
      sitting, and upright. RESULTS: The median percentage and interquartile range
      (IQR) of time spent lying, sitting, and upright recorded by the device were 36%
      (15-68), 51% (28-72), and 2% (1-5), respectively. Agreement between the methods
      was substantial: Intraclass Correlation Coefficient (95% CI): lying 0.74 (0.46
      0.89), sitting 0.68 (0.36-0.86), and upright 0.72 (0.43-0.88). CONCLUSION:
      Patients are inactive in an acute stroke setting. In acute stroke, estimates of
      time spent lying, sitting, and upright measured by a device are valid.

PMID- 24282816
TI  - Hepatitis C virus NS3 inhibitors: current and future perspectives.
AB  - Currently, hepatitis C virus (HCV) infection is considered a serious health-care
      problem all over the world. A good number of direct-acting antivirals (DAAs)
      against HCV infection are in clinical progress including NS3-4A protease
      inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well
      as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and
      boceprevir) have been recently approved for the treatment of hepatitis C in
      combination with standard of care (pegylated interferon plus ribavirin). The new
      therapy has significantly improved sustained virologic response (SVR); however,
      the adverse effects associated with this therapy are still the main concern. In
      addition to the emergence of viral resistance, other targets must be continually
      developed. One such underdeveloped target is the helicase portion of the HCV NS3
      protein. This review article summarizes our current understanding of HCV
      treatment, particularly with those of NS3 inhibitors. 

PMID- 24282817
TI  - Carbohydrate 19.9 antigen serum levels in liver disease.
AB  - BACKGROUND: Carbohydrate 19.9 antigen (CA19.9) has been used in the diagnosis and
      followup of gastrointestinal tumours. The aim of this prospective longitudinal
      study was the evaluation of CA19.9 levels in patients with chronic hepatitis and
      hepatic cirrhosis hepatitis C virus and B virus correlated. MATERIALS AND
      METHODS: 180 patients were enrolled, 116 with HCV-related chronic liver disease
      (48% chronic hepatitis, 52% cirrhosis) and 64 with HBV-related chronic liver
      disease (86% chronic hepatitis, 14% cirrhosis). Patients with high levels of
      CA19.9 underwent abdominal ecography, gastroendoscopy, colonoscopy, and abdominal
      CT scan. RESULTS: 51.7% of patients with HCV-related chronic liver disease and
      48.4% of those with HBV-related chronic liver disease presented high levels of
      CA19.9. None was affected by pancreatic or intestinal neoplasia, cholestatic
      jaundice, or other diseases potentially able to induce Ca19.9 elevations. CA19.9
      levels were elevated in 43.3% of HCV chronic hepatitis, in 56.3% of HCV
      cirrhosis, in 45.1% of HBV chronic hepatitis, and in 58% of HBV cirrhosis.
      CONCLUSIONS: CA19.9 commonly increases in the serum of patients with chronic
      viral hepatitis. Elevation of CA 19.9 is not specific for neoplastic disease and
      is related to the severity of fibrosis and to the viral aetiology of hepatitis.

PMID- 24282818
TI  - What is the best strategy for enhancing the effects of topically applied ozonated
      oils in cutaneous infections?
AB  - Owing to diabetes, atherosclerosis, and ageing, there are several million
      patients undergoing skin lesions degenerated into infected ulcers with very
      little tendency to heal and implying a huge socioeconomical cost. Previous
      medical experience has shown that the daily application of ozonated oil
      eliminates the infection and promotes a rapid healing. The purpose of the study
      is the optimization of the antimicrobial effect of ozonated oils by testing in
      vitro four bacterial species and one yeast without or in the presence of
      different amounts of human serum. The results obtained suggest that a gentle and
      continuous removal of debris and exudate is an essential condition for the potent
      bactericidal effect of ozonated oils. In fact, even small amounts of human serum
      inactivate ozone derivatives and protect bacteria. The application of ozonated
      oil preparations is very promising in a variety of skin and mucosal infections.
      Moreover, ozonated oils are far less expensive than antibiotic preparations. 

PMID- 24282819
TI  - Folic acid-chitosan conjugated nanoparticles for improving tumor-targeted drug
      delivery.
AB  - OBJECTIVE: To prepare folic acid-chitosan conjugated nanoparticles (FA-CS NPs)
      and evaluate their targeting specificity on tumor cells. METHODS: Chitosan (CS)
      NPs were prepared by ionic cross linking method, and folic acid (FA) was
      conjugated with CS NPs by electrostatic interaction. The properties of NPs were
      investigated, and doxorubicin hydrochloride (Dox) as a model drug was
      encapsulated for investigating drug release pattern in vitro. The cytotoxicity
      and cellular uptake of FA-CS NPs were also investigated. RESULTS: The results
      reveal that the obtained FA-CS NPs were monodisperse nanoparticles with suitable
      average size and positive surface charge. Dox was easily loaded into FA-CS NPs,
      and the release pattern showed a long and biphasic drug release. Noticeable
      phagocytosis effect was observed in the presence of rhodamine B-labeled FA-CSNPs
      when incubating with the folate receptor-positive SMMC-7221 cells. CONCLUSION:
      Compared with the unmodified CS NPs, FA-CS NPs showed much higher cell uptaking
      ability due to the known folate-receptor mediated endocytosis. FA-CS NPs provide
      a potential way to enhance the using efficiency of antitumor drug by folate
      receptor mediated targeting delivery.

PMID- 24282820
TI  - Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its
      incidence, pathophysiology, clinical relevance, and treatment.
AB  - Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted
      anticancer therapy which targets different growth factor receptors and hence
      attenuates cancer cell survival and growth. Since their introduction as adjunct
      treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a
      number of reports have demonstrated that TKI can induce thyroid dysfunction which
      was especially more common with sunitinib maleate. Many mechanisms with respect
      to this adverse effect of tyrosine kinase inhibitors have been proposed including
      their induction of thyroiditis, capillary regression in the thyroid gland,
      antithyroid peroxidase antibody production, and their ability to decrease iodine
      uptake by the thyroid gland. Of interest is the observation that TKI-induced
      thyroid dysfunction may actually be protective as it was shown to improve overall
      survival, and it was suggested that it may have a prognostic value. Followup on
      thyroid function tests while patients are maintained on tyrosine kinase inhibitor
      is strongly recommended. When thyroid dysfunction occurs, appropriate treatment
      should be individualized depending on patients symptoms and thyroid stimulating
      hormone level. 

PMID- 24282821
TI  - Effect of alcohol on diffuse axonal injury in rat brainstem: diffusion tensor
      imaging and aquaporin-4 expression study.
AB  - The aim of this study is to assess the effects of alcohol on traumatic brain
      injury by using diffusion tensor imaging (DTI) and evaluate aquaporin-4(AQP4)
      expression changes in rat brainstems following acute alcohol intoxication with
      diffuse axonal injury (DAI). We further investigated the correlation between the
      AQP4 expression and DTI in the brain edema. Eighty-five rats were imaged before
      and after injury at various stages. DTI was used to measure brainstem apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA), with immunostaining
      being used to determine AQP4 expression. After acute alcoholism with DAI, ADC
      values of the brainstem first decreased within 6 h and then elevated. FA values
      began to decline by 1 h, reaching a minimum at 24 h after trauma. There was a
      negative correlation between ADC values and brainstem AQP4 expression at 6 h and
      positive correlation at 6 h to 24 h. Changes of ADC and FA values in DAI with
      acute alcoholism indicate the effects of ethanol on brain edema and the severity
      of axonal injury. The correlations between ADC values and the brainstem AQP4
      expression at different time points suggest that AQP4 expression follows an
      adaptative profile to the severity of brain edema.

PMID- 24282822
TI  - Prevalence and antibiotic resistance pattern of methicillin-resistant
      Staphylococcus aureus from an orthopaedic hospital in Nigeria.
AB  - Patients with surgical wounds have been reported to be at high risk of MRSA
      carriage and infection. The prevalence and antibiotic resistance pattern of this
      organism in the orthopaedic ward of Ahmadu Bello University Teaching Hospital
      (ABUTH), Zaria-Nigeria, a 547-bed Nigerian hospital, were thus studied. A total
      of 185 isolates of Staphylococcus aureus were confirmed from 217 samples taken
      from the orthopaedic wards of the hospital using standard isolation methods. Out
      of these, 44 (23.8%) were from the wounds of patients and 70 (37.8%) from the
      skin. The remaining 65 (35.1%) and 6 (3.2%) were from their beds and the
      atmospheric air, respectively. Out of these, 33 (75%), 36 (51.4%), and 48 (73.8%)
      from wounds, skin, and bed, respectively, were found to be methicillin-resistant
      Staphylococcus aureus (MRSA) using the disc-sensitive test methods. None was
      detected from the atmosphere. The antibiotic susceptibility pattern results
      showed the level of resistance to be ampicillin 100% in all the three sites,
      pefloxacin 90.9%, 72.2%, 66.7%, ceftriaxone 69.7%, 72.2%, 70.8%, gentamicin
      54.5%, 52.8%, 37.5%, and ciprofloxacin 51.5%, 47.2%, 35.4% at the wound, skin,
      and bed sites, respectively. Results confirm that MRSA continues to pose a threat
      to the hospitalized patients, especially those with bone and wound infections. 

PMID- 24282823
TI  - The impact of hyperglycemic emergencies on the kidney and liver.
AB  - Studies on the alterations of liver and kidney function parameters in patients
      with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) were limited.
      Participants with DKA, DK, non-DK, and healthy controls were enrolled in the
      current study. Parameters of liver and kidney function were measured and
      evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin
      A1c (HbA1c), uric acid, and creatinine but lower levels of transferases and
      protein compared with the other three groups (P < 0.05 for all). The patients
      with DK had higher levels of plasma glucose and HbA1c but lower levels of
      glutamyl transpeptidase and protein compared with the non-DK and control groups
      (P < 0.05). Prealbumin levels were significantly reduced in the severe DKA
      patients compared with the mild/moderate DKA patients. Serum prealbumin levels
      were correlated with albumin levels (r = 0.401, P = 0.010), HCO3 (r = 0.350, P =
      0.027), and arterial pH (r = 0.597, P < 0.001) in the DKA patients. A diagnostic
      analysis showed that lower prealbumin levels significantly reflected the presence
      of hyperglycemic emergencies (P < 0.001). Liver and kidney function parameters
      deteriorated, especially in DKA. Prealbumin levels can be of value in detecting
      the presence of hyperglycemic crisis. This clinical trial is registered with
      ChiCTR-OCH-12003077. 

PMID- 24282824
TI  - Formation of the tetranuclear, tetrakis-terminal-imido Mn4(IV)(N(t)Bu)8 cubane
      cluster by four-electron reductive elimination of (t)BuN=N(t)Bu. The role of the
      s-block ion in stabilization of high-oxidation state intermediates.
AB  - Mn4(IV)(MU3-N(t)Bu)4(N(t)Bu)4 is obtained from a previously reported asymmetric
      Mn(IV/V)-Li-(NR)(N) cluster by the removal of Li from the starting cluster by ion
      metathesis, which triggers reductive elimination of azo-tert-butane to give a
      tetranuclear heterocubane cluster. 

PMID- 24282825
TI  - Carbonic acid: molecule, crystal and aqueous solution.
AB  - Carbonic acid (CA) is a crucial species in the equilibrium between carbon
      dioxide, water and many minerals. Yet many of its properties have either not been
      studied at all, or have been misunderstood. Its short lifetime in the presence of
      moisture has been a major stumbling block in efforts to studying it. Over the
      last two decades, there has been a sustained, albeit slow progress in the
      detection, synthesis and investigations of CA in its various phases - as a
      molecule in gas phase, in its crystalline state, as an adsorbate on mineral
      surfaces and in aqueous solutions. For instance, ultrafast time resolved
      spectroscopic experiments as well as molecular dynamics based free energy
      calculations using Kohn-Sham density functional theory have shown the pKa of CA
      to be around 3.5 which makes its acidity comparable to that of formic acid. The
      composition of its gas phase in terms of its conformer and oligomer population
      have also been examined. Thin films of crystalline carbonic acid polymorphs have
      been synthesized and characterized using infrared and Raman spectra. Given the
      difficulties associated in the conduct of experiments to investigate CA,
      computational modelling has played a significant role. Using a multi-tiered
      modelling approach, we have been able to examine several model crystal structures
      possessing distinctive hydrogen bonding motifs. Their vibrational spectra were
      compared against those obtained from experiments. A model crystal consisting of
      hydrogen bonded molecules in a chain-like fashion fits the experimental
      vibrational spectra of beta-carbonic acid better than one in which the motif is
      two-dimensional (sheet-like). Under dry conditions, we predict such a crystal to
      be stable below 359 K at 1 atm. In this feature article, we provide a summary of
      our work on carbonic acid as well as review contributions from others. 

PMID- 24282826
TI  - Preparation and affinity-based purification of caged linear DNA for light
      controlled gene expression in mammalian cells.
AB  - A facile and useful method for preparing caged DNAs was developed. The method
      includes a caging reaction of a linear dsDNA having a minimal sequence of protein
      expression with Bio-Bhc-diazo and affinity separation of the caged DNA. Effective
      suppression and photo-mediated restoration of protein expression were
      demonstrated. 

PMID- 24282827
TI  - A cubic dipole lattice of water molecules trapped inside carbon cages.
AB  - We report the crystal structure and dielectric properties of a pure H2O@C60
      crystal at low temperature. The caged water molecules free from the hydrogen
      bonds rotate even at 8 K. The antifreeze rotating water molecules respond to an
      external electric field due to their permanent dipole moment. 

PMID- 24282828
TI  - Transforming TMA governance--proposed changes to the annual meeting and the House
      of Delegates.

PMID- 24282830
TI  - Credit card payment, urine screens & doctor shopping.

PMID- 24282831
TI  - Taking the pulse of Tennessee's ehealth initiatives.

PMID- 24282832
TI  - EHRs: boon or bane?

PMID- 24282833
TI  - Physician suicide rates Show alarming need for education.

PMID- 24282834
TI  - Know your rights under the silent PPO law.

PMID- 24282835
TI  - Milton and me.

PMID- 24282836
TI  - McArdle's disease: a clinical review and case report.
AB  - McArdle's Disease is a rare glycogen disease involving deficiency in muscle
      phosphorylase. This deficiency can lead to rhabdomyolysis and subsequently renal
      failure. McArdle's Disease has a similar presentation as several other metabolic
      myopathies with exercise-induced fatigue, myalgias, weakness or unexplained
      rhabdomyolysis. Suspicion should be raised in the presence of unexplained
      symptoms, and muscle biopsy can be done to confirm the diagnosis.

PMID- 24282837
TI  - Discordant B- and T-cell non-Hodgkin's lymphoma: case report and review of
      literature.

PMID- 24282838
TI  - Veillonella as a cause for septic pulmonary emboli.
AB  - We are reporting a case of a 63-year-old-male patient with an unusual
      presentation of multiple lung abscesses. The patient likely had septic pulmonary
      emboli secondary to periodontal disease. The implicated organism was Veillonella
      species. Veillonella are anaerobe bacteria that traditionally been considered
      nonpathogenic flora.

PMID- 24282839
TI  - Social Security income measurement in two surveys.
AB  - As a major source of income for retired persons in the United States, Social
      Security benefits directly influence economic well-being. That fact underscores
      the importance of measuring Social Security income accurately in household
      surveys. Using Social Security Administration (SSA) records, we examine Social
      Security income as reported in two Census Bureau surveys, the Survey of Income
      and Program Participation (SIPP) and the Current Population Survey (CPS).
      Although SSA usually deducts Medicare premiums from benefit payments, both the
      CPS and the SIPP aim to collect and record gross Social Security benefit amounts
      (before Medicare premium deductions). We find that the Social Security benefit
      recorded in the CPS closely approximates the gross benefit recorded for CPS
      respondents in SSA's records, but the Social Security benefit recorded in the
      SIPP more closely approximates SSA's record of net benefit payments (after
      deducting Medicare premiums).

PMID- 24282840
TI  - Prevalence, characteristics, and poverty status of Supplemental Security Income
      multirecipients.
AB  - "Multirecipients" are people who receive Supplemental Security Income (SSI)
      payments while living with other recipients (not including an SSI-eligible
      spouse). Using Social Security Administration records matched to Current
      Population Survey data for 2005, this article examines multirecipients' personal,
      family, household, and economic characteristics. I find that no more than 20
      percent of the 2005 SSI population were multirecipients. Most multirecipients
      were adults, lived with one other recipient, and/or shared their homes with
      related recipients. Multirecipients were generally less likely to be poor than
      SSI recipients as a whole; but those who were children, lived with one other
      recipient, and/or shared their homes with a nonrecipient were more likely to be
      poor. Implementing sliding-scale SSI benefit reductions for children in
      multirecipient households would affect about 23 percent of multirecipients, or
      about 5 percent of all SSI recipients.

PMID- 24282841
TI  - Disability shocks near retirement age and financial well-being.
AB  - Using Health and Retirement Study data, we examine three groups of adults aged 51
      56 in 1992 with different disability experiences over 8 years. Our analysis
      reveals three major findings. First, people who started and stayed nondisabled
      experienced stable financial security, with improvement in household wealth
      despite labor force withdrawal. Second, the newly disabled--people who started as
      nondisabled but suffered a disability shock--experienced increased poverty rates
      and decreased median incomes. Average earnings loss was the greatest for them,
      with public and private benefits replacing less than half of the loss, whereas
      increased public health insurance coverage alleviated reduced private health
      insurance coverage. The newly disabled experienced improvement in household
      wealth, although at a lower rate compared with those who stayed nondisabled.
      Third, people who started and stayed disabled were behind at the baseline and
      have fallen further behind on most measures, except for improvement in health
      insurance coverage.

PMID- 24282842
TI  - Pension plan participation among married couples.
AB  - We present descriptive statistics on pension participation and types of pensions
      among married couples, using data from the 1996/2008 Panels of the Survey of
      Income and Program Participation and Social Security administrative records.
      Previous research has focused on pension coverage by marital status, but has not
      examined couples as a unit. Because couples usually share income, viewing them as
      a unit provides a better picture of potential access to income from retirement
      plans. Our analysis compares 1998 and 2009 data because substantial changes
      occurred in the pension landscape over this decade that could have influenced the
      prevalence of different pension plans, although we observe modest changes in
      participation rates and types of plans over the period. We find that in 20
      percent of couples, neither spouse participated in a pension plan; in 10 percent,
      the wife was the only participant; and in 37 percent, the husband was the only
      participant.

PMID- 24282843
TI  - Youth transitioning out of foster care: an evaluation of a Supplemental Security
      Income policy change.
AB  - Youths with disabilities face numerous challenges when they transition to
      adulthood. Those who are aging out of foster care face the additional challenge
      of losing their foster care benefits, although some will be eligible for
      Supplemental Security Income (SSI) payments after foster care ceases. However,
      the time needed to process SSI applications exposes those youths to a potential
      gap in the receipt of benefits as they move between foster care and SSI. We
      evaluate the effects of a 2010 Social Security Administration policy change that
      allows such youths to apply for SSI payments 60 days earlier than the previous
      policy allowed. The change provides additional time for processing claims before
      the applicant ages out of the foster care system. We examine administrative
      records on SSI applications from before and after the policy change to determine
      if the change has decreased the gap between benefits for the target population.

PMID- 24282844
TI  - When a mother wants to deliver with a midwife at home.
AB  - In this special issue of The Journal of Clinical Ethics, different views on both
      the ethical desirability of women delivering in hospitals or at home with
      midwives are discussed. What careproviders, including midwives, should recommend
      to mothers in regard to the place of giving birth is considered. Emotional
      concerns likely to be of importance to mothers, fathers, midwives, and doctors
      are also presented. Finally, possible optimal approaches at the levels of both
      policy and the bedside are suggested.

PMID- 24282845
TI  - Planned home birth in the United States and professionalism: a critical
      assessment.
AB  - Planned home birth has been considered by some to be consistent with professional
      responsibility in patient care. This article critically assesses the ethical and
      scientific justification for this view and shows it to be unjustified. We
      critically assess recent statements by professional associations of
      obstetricians, one that sanctions and one that endorses planned home birth. We
      base our critical appraisal on the professional responsibility model of obstetric
      ethics, which is based on the ethical concept of medicine from the Scottish and
      English Enlightenments of the 18th century. Our critical assessment supports the
      following conclusions. Because of its significantly increased, preventable
      perinatal risks, planned home birth in the United States is not clinically or
      ethically benign. Attending planned home birth, no matter one's training or
      experience, is not acting in a professional capacity, because this role
      preventably results in clinically unnecessary and therefore clinically
      unacceptable perinatal risk. It is therefore not consistent with the ethical
      concept of medicine as a profession for any attendant to planned home birth to
      represent himself or herself as a "professional." Obstetric healthcare
      associations should neither sanction nor endorse planned home birth. Instead,
      these associations should recommend against planned home birth. Obstetric
      healthcare professionals should respond to expressions of interest in planned
      home birth by pregnant women by informing them that it incurs significantly
      increased, preventable perinatal risks, by recommending strongly against planned
      home birth, and by recommending strongly for planned hospital birth. Obstetric
      healthcare professionals should routinely provide excellent obstetric care to all
      women transferred to the hospital from a planned home birth.The professional
      responsibility model of obstetric ethics requires obstetricians to address and
      remedy legitimate dissatisfaction with some hospital settings and address
      patients' concerns about excessive interventions. Creating a sustained culture of
      comprehensive safety, which cannot be achieved in planned home birth, informed by
      compassionate and respectful treatment of pregnant women, should be a primary
      focus of professional obstetric responsibility.

PMID- 24282846
TI  - Ethics and the architecture of choice for home and hospital birth.
AB  - In this issue of The Journal of Clinical Ethics, we offer a variety of
      perspectives on the moral and medical responsibilities of professionals with
      regard to a woman's choice of where she will birth her baby. The articles in this
      special issue focus on place of birth, but they have larger resonance for
      clinicians whose decisions about providing the best possible care require them to
      sort through evidence, consider their own possible biases and the limitations of
      their training, and balance the wishes of their patients with the demands of
      colleagues, hospitals, and insurers. The articles published in this special issue
      of The Journal of Clinical Ethics will help those who wrestle with such dilemmas
      in everyday clinical decision making.

PMID- 24282847
TI  - Revisiting "The maximin strategy in modern obstetrics".
AB  - Published in 1981, "The Maximin Strategy in Modern Obstetrics" offered two
      claims: first, that obstetrical interventions ought to be assessed not singly,
      but rather as packages of interconnected measures that could cumulatively
      increase risks of harm; and second, that many of these interventions, considered
      either singly or as a package, lacked a sound evidence base. The first claim has
      been well supported by later literature, although the term "cascade effect" has
      proven a more felicitous descriptor for the phenomenon of interventions that
      trigger the use of other interventions to monitor, prevent, or treat possible
      side-effects. The second claim was initially supported in a very inadequate way,
      since the "Maximin" article appeared before an understanding of the methods of
      systematic reviews of medical evidence had been widely promulgated. Despite these
      defects, subsequent, rigorously conducted systematic reviews have tended to
      confirm the impression first offered in 1981, that practices that support
      physiologic childbearing and the innate, hormonally driven capacities of
      childbearing women and their fetuses/newborns are much more in keeping with the
      available evidence than practices involving common or routine high-technology
      interference with physiologic processes. Harm may occur either directly, through
      high-technology interventions, or when such procedures distract attention and
      resources from safe, effective biological processes and lower-technology
      measures. Surveys indicate a lack of knowledge of this evidence among
      childbearing women, signaling a serious ethical deficiency in shared decision
      making processes and perhaps the skills and knowledge of maternity care
      clinicians.

PMID- 24282848
TI  - A reconsideration of home birth in the United States.
AB  - Home births continue to constitute only a small percentage of all deliveries in
      the United States, in part because of concerns about their safety. While the
      literature is decidedly mixed in regard to the degree of risk, there are several
      studies that report that home birth may at times entail a small absolute increase
      in perinatal risks in circumstances that cannot always be anticipated prior to
      the onset of labor. While the definition of "small" will vary between
      individuals, and publications vary in the level of risk they ascribe to birth at
      home, studies with the least methodological flaws and with adequate power often
      cite an excess death rate in the range of one per thousand. Home birth is, in
      that regard, but one example of patients' choices and plans that sometimes carry
      increased risk or include alternatives that individual physicians feel
      uncomfortable supporting or recommending. Our intention in this opinion piece is
      not to advocate for or against home birth. Rather, we recognize that home birth
      is but one example of a patient choice that might differ from what a provider
      feels is in a woman's best interests. In this article we will discuss ethical
      considerations in such circumstances using home birth as an example. We consider
      in this article how the ethical principles of respect for autonomy and non
      maleficence can be balanced using, among other examples, the choice by some for a
      home birth. We discuss how absolute rather than relative risk should guide
      individuals' evaluation of patient choices. We also consider how in some
      circumstances, the value and safety added by a physician's participation may
      outweigh a potentially small increment in absolute risk that might result from a
      patient's decision to deliver at home because of a perceived physician
      endorsement. We recognize, however, that doctors and midwives participating in
      choices they have not recommended, or may even believe will lead to or increase
      risk for adverse outcomes, presents dilemmas and raises important questions. When
      does respect for patient choice and autonomy become support for poor decision
      making? When is participation not respectful but enabling? Finally we discuss the
      role and responsibility of organized medicine in making all births as safe as
      possible.

PMID- 24282849
TI  - The absolute power of relative risk in debates on repeat cesareans and home birth
      in the United States.
AB  - BACKGROUND: Changes in policies and practices related to repeat cesareans and
      home birth in the U.S. have been influenced by different interpretations of the
      risk of poor outcomes. METHODS: This article examines two cases-vaginal birth
      after cesarean (VBAC) and home birth to illustrate how an emphasis on relative
      over absolute risk has been used to characterize outcomes associated with these
      practices. The case studies will rely on reviews of the research literature and
      examination of data on birth trends and outcomes. RESULTS: Childbirth involves
      some unique challenges in assessing health risks, specifically the issues of: (1)
      timing of risks (lowering health risk in a current birth can increase it in
      subsequent births); (2) the potential weighing of risks to the mother's versus
      the infant's health; (3) the fact that birth is a condition of health and many of
      the feared outcomes (for example, symptomatic uterine rupture) involve very low
      absolute risk of occurrence; and (4) a malpractice environment that seizes upon
      those rare poor outcomes in highly publicized lawsuits that receive widespread
      attention in the clinical community. In the cases of VBAC and home birth, the
      result has been considerable emphasis on relative risks, typically an adjusted
      odds ratio, with little consideration of absolute risks. CONCLUSION: Assessments
      of the safety of interventions in childbirth should involve careful consideration
      and communication of the multiple dimensions of risk, particularly a balancing of
      relative and absolute risks of poor health outcomes.

PMID- 24282850
TI  - Moral science: ethical argument and the production of knowledge about place of
      birth.
AB  - Ethical arguments about caregiver responsibility and the limits of client
      autonomy rely on best evidence about the risks and benefits of medical
      interventions. But when the evidence is unclear, or when the peer-reviewed
      literature presents conflicting accounts of the evidence, how are clinicians and
      their clients to recommend or decide the best course of action? Conflicting
      evidence about the outcomes of home and hospital birth in the peer-reviewed
      literature offers an opportunity to explore this question. We present the
      contrary evidence and describe the social and cultural elements that influence
      the production of the science of birth, including professional, publication, and
      critical bias. We then consider how the science of birth has been used an misused
      in making ethical arguments about preferred place of birth. We conclude with a
      number of recommendations about the responsible use of the evidence, arguing for
      an "ethics of information" that can be drawn on to guide caregivers and clients
      in the use of evidence for clinical decision making.

PMID- 24282851
TI  - Women's perceptions of childbirth risk and place of birth.
AB  - In the United States, clinical interventions such as epidurals, intravenous
      infusions, oxytocin, and intrauterine pressure catheters are used almost
      routinely in births in the hospital setting, despite evidence that the
      overutilization of such interventions likely plays a key role in increasing the
      need for cesarean section (CS).' In 2010, according to the U.S. Centers for
      Disease Control and Prevention, approximately 32.8 percent of births in the U.S.
      were by CS.2 The U.S. National Institutes of Health has reported that CS
      increases avoidable maternal and neonatal morbidity and mortality.3To increase
      understanding of what might motivate the overuse of CS in the U.S., we
      investigated the factors that influenced women's decision making around
      childbirth, because women's conscious and unconscious choices about giving birth
      could influence whether they would choose or allow delivery by CS. In this
      article, we report findings about women's decisions related to place of birth-at
      home or in a hospital. We found that choosing a place of birth was significant in
      how women in our study attempted to mitigate their perceptions of the risks of
      childbirth for themselves and their infant. Concern for the safety of the infant
      was a central, driving factor in the decisions women made about giving birth, and
      this concern heightened their perceptions of the risks of childbirth. Heightened
      perceptions of risk about the safety of the fetus during childbirth were found to
      affect women's ability to accurately assess the risk of using clinical
      interventions such as the time of admission, epidural anesthesia, oxytocin, or
      cesarean birth, which has important implications for clinical practice, prenatal
      education, perinatal research, medical decision making, and informed consent.

PMID- 24282852
TI  - Exceptional deliveries: home births as ethical anomalies in American obstetrics.
AB  - Interest in home birth appears to be growing among American women, and most
      obstetricians can expect to encounter patients who are considering home birth. In
      2011, the American College of Obstetricians and Gynecologists (ACOG) issued an
      opinion statement intended to guide obstetricians in responding to such patients.
      In this article, I examine the ACOG statement in light of the historical and
      contemporary clinical realities surrounding home birth in the United States, an
      examination guided in part by my own experiences as an obstetrician in home-birth
      friendly and home-birth-unfriendly medical milieus. Comparison with other
      guidelines indicates that ACOG treats home birth as an ethical exception:
      comparable evidence leads to strikingly different recommendations in the case of
      home birth and the case of trial of labor following a prior cesarean; and ACOG
      treats other controversial issues that involve similar ethical questions quite
      differently. By casting the provision of information as not just the primary but
      the sole ethical responsibility of the obstetrician, ACOG statement obviates
      obstetricians' responsibilities to provide appropriate clinical care and to make
      the safest possible clinical environment for those mothers who choose home birth
      and for their newborns. What, on its face, seems to be a statement of respect for
      women's autonomy, implicitly authorizes behaviors that unethically restrain truly
      autonomous choices. Obstetricians need not attend home births, I argue. Our
      ethical duties do, however, oblige us (1) to refer clients to skilled clinicians
      who will attend home birth, (2) to continue respectful antenatal care for those
      women choosing home birth, (3) to provide appropriate consultation to home birth
      attendants, and (4) to ensure that transfers of care are smooth and nonpunitive.

PMID- 24282853
TI  - Being safe: making the decision to have a planned home birth in the United
      States.
AB  - Although there is evidence that supports the safety of planned home birth for
      healthy women, less than 1 percent of women in the United States choose to have
      their baby at home. An ethnographic study of the experience of planned home birth
      provided rich descriptions of women's experiences planning, preparing for, and
      having a home birth.This article describes findings related to how women make the
      decision to have a planned home birth. For these women, being safe emerged as
      central in making the decision. For them, being safe included four factors:
      avoiding technological birth interventions, knowing the midwife and the midwife
      knowing them, feeling comfortable and protected at home, and knowing that backup
      hospital medical care was accessible if needed.

PMID- 24282854
TI  - Facilitating women's choice in maternity care.
AB  - Maternity careproviders often have strong views concerning a woman's choice of
      where to give birth.These views may be based on the ethical principle of
      autonomy, or on the principle of beneficence. The authors propose that an
      approach utilizing shared decision making allows careproviders and women to move
      beyond disagreements regarding which evidence on risk should "counts' instead
      adopting a process of increased knowledge and support for women and their partner
      while they make choices regarding place of birth.

PMID- 24282855
TI  - One obstetrician's look at a polarizing birth arena.
AB  - Birth, whether at home or in the hospital, should involve shared decision making
      that empowers women to choose or decline the interventions that are best for the
      woman and her baby. Obstetricians and home birth midwives must share important
      information with their patients.

PMID- 24282856
TI  - Seeking an alternative baseline for birth.
AB  - Birth is a spiritual experience for mother and baby. Women need information and
      psychological preparation before birth, and a knowledgeable companion during
      birth. Unless medical intervention is needed, medical personnel should step back
      and stay out of the way.

PMID- 24282857
TI  - Individual versus professional preferences.
AB  - The author, the mother of two children in Amsterdam, describes her birth
      experiences, the first in the hospital, the second at home.

PMID- 24282858
TI  - The industry take-over of home birth and death.
AB  - The generation in the United States who renewed interest in home birth is also
      returning to the tradition of funeral care at home. Caring for your own dead at
      home is legal in all 50 U.S. states.

PMID- 24282859
TI  - On the need for a real choice.
AB  - For low-risk mothers who do not wish to give birth in a hospital, a nearby birth
      center led by midwives is an excellent option.

PMID- 24282860
TI  - Legal briefing: home birth and midwifery.
AB  - This issue's "Legal Briefing" column covers recent legal developments involving
      home birth and midwifery in the United States. Specifically, we focus on new
      legislative, regulatory, and judicial acts that impact women's' access to direct
      entry (non-nurse) midwives. We categorize these legal developments into the
      following 12 categories. 1. Background and History 2. Certified Nurse-Midwives 3.
      Direct Entry Midwives 4. Prohibition of Direct Entry Midwives 5. Enforcement of
      Prohibition 6. Challenges to Prohibition 7. Forbearance without License 8.
      Voluntary Licensure 9. Unclear and Uncertain Status 10. Growth of DEM Licensure
      11. Licensure Restrictions 12. Medicaid Coverage

PMID- 24282861
TI  - Time to convene?

PMID- 24282862
TI  - Show me the money.

PMID- 24282863
TI  - Case report: management of broken dental needles in practice.
AB  - Breakage of a dental needle is a rare but significant complication of local
      anaesthetic injections, which causes great anxiety for the patient and dental
      surgeon, and necessitates investigations and further treatment. It may have
      important medico-legal considerations. We describe a case where a dental needle
      broke during the routine administration of an inferior alveolar nerve block for a
      dental procedure. This broken needle subsequently migrated to the lateral aspect
      of the neck, confirming that these 'migrations' do occur. We discuss the various
      causes, and clinical and dentolegal implications, as well as methods of
      treatment.

PMID- 24282864
TI  - An audit of orthodontic treatment eligibility among new patients referred to a
      Health Service Executive orthodontic referral centre.
AB  - AIM: The aim of this audit was to evaluate orthodontic treatment eligibility
      among new patients referred for assessment from primary dental care clinics in
      the Health Service Executive (HSE) South region to a HSE orthodontic referral
      centre. METHOD: A data collection form was designed and applied prospectively to
      consecutive new patient referrals who attended diagnostic clinics at the
      Orthodontic Unit, Cork University Dental School and Hospital, between October
      2011 and February 2012. Orthodontic treatment eligibility was based on guidelines
      introduced by the HSE in 2007. RESULTS: Data on 291 patients (147 males and 144
      females) with a mean age of 11.6 years (SD +/- 2.4 years; range 8-19 years) were
      evaluated. Of the 83 (29%) patients eligible for orthodontic treatment under the
      guidelines, the most commonly diagnosed malocclusion traits were a crossbite with
      greater than 2 mm discrepancy between retruded contact position and intercuspal
      position (24 patients), followed by an overjet greater than 9 mm (21 patients).
      CONCLUSIONS: A total of 29% of new patient referrals were deemed eligible for
      orthodontic treatment under HSE eligibility guidelines introduced in 2007.
      Reduction of new patient referrals not eligible for treatment, under these
      guidelines, is required to enable more efficient use of resources.

PMID- 24282865
TI  - Audit of the Health Service Executive orthodontic referral pathway between 2009
      and 2011 in the Dublin Mid-Leinster region.
AB  - An audit was undertaken in 2009 to determine the success of the new national
      orthodontic referral protocol introduced to the Health Service Executive (HSE) in
      2007 and operated in the Dublin Mid-Leinster HSE region. It was repeated in 2011
      to determine if the HSE austerity measures have had a bearing on the orthodontic
      service performance in the Dublin Mid-Leinster HSE region. The audit also
      measured the success of referring practitioners in identifying the correct Index
      of Orthodontic Treatment Need (IOTN) classification of the patient. In the 2011
      audit, the figures were broken down to identify the occlusal variables that
      caused dental practitioners most difficulties in identification. The audit
      demonstrates a good referral to assessment timeframe in 2009 (85-80% compliance
      for IOTN 5 and 4 within three to six months, respectively), which deteriorates
      significantly in 2011 (26-4% for IOTN 5 and 4 within three to six months,
      respectively). The ability of dentists to identify the correct IOTN
      classification was better in 2009 (60% correct) compared to 2011 (51% correct),
      but both figures fell below the audit standard of 75% of referrals with correct
      IOTN classifications. The IOTN occlusal dental health components most readily
      identified by referring practitioners and meeting audit standards were 5a
      (overjet >9mm), 5i (impacted teeth) and 5h (extensive hypodontia). The remaining
      occlusal dental health components in the HSE IOTN fell below the audit standard.
      The audit clearly identifies a requirement for a continued educational effort to
      maintain the HSE IOTN skill base in primary care, and a need for additional
      resources to manage the demand for orthodontic assessments.

PMID- 24282866
TI  - A simple technique for replacing extracted anterior teeth using a vacuum formed
      retainer.
AB  - This technique can be used as an immeciate short-term solution after extraction,
      implant placement or grafting procedures. Long-term use is not appropriate and it
      is not suitable where there is poor hygiene or a high smile line where the
      junction of the flange and soft tissue would be conspicuous. This device is
      easily removed to facilitate hygiene, it is available almost immediately, is
      inexpensive, comfortable to wear, conservative of abutment teeth and can be
      relieved of soft tissue contact. It is not appropriate in situations where
      occlusal units are required, where multiple teeth are to be extracted, where
      there are high aesthetic demands or when a long-term solution is required.

PMID- 24282867
TI  - Evaluation of the plaque removal efficacy of a water flosser compared to string
      floss in adults after a single use.
AB  - OBJECTIVE: To compare the plaque removal efficacy of a water flosser to string
      floss combined with a manual toothbrush after a single use. METHODS: Seventy
      adult subjects participated in this randomized, single-use, single-blind,
      parallel clinical study. Subjects were assigned to one of two groups; Waterpik
      Water Flosser plus a manual toothbrush (WF) or waxed string floss plus a manual
      toothbrush (SF). Each participant brushed for two minutes using the Bass
      technique. The WF group added 500 ml of warm water to the reservoir and followed
      the manufacturer's instructions, and the SF group used waxed string floss between
      each tooth, cleaning the mesial and distal surfaces as instructed. Subjects were
      observed to ensure they covered all areas and followed instructions. Scores were
      recorded for whole mouth, marginal, approximal, facial, and lingual regions for
      each subject using the Rustogi Modification of the Navy Plaque Index. RESULTS:
      The WF group had a 74.4% reduction in whole mouth plaque and 81.6% for approximal
      plaque compared to 57.7% and 63.4% for the SF group, respectively (p < 0.001).
      The differences between the groups showed the water flosser was 29% more
      effective than string floss for overall plaque removal and approximal surfaces
      specifically (p < 0.001). The WF group was more effective in removing plaque from
      the marginal, lingual, and facial regions; 33%, 39%, and 24%, respectively (p <
      0.001). CONCLUSION: The Waterpik Water Flosser and manual toothbrush is
      significantly more effective than a manual brush and string floss in removing
      plaque from tooth surfaces.

PMID- 24282868
TI  - Clinical evaluation of an enhanced white light and fluorescence device for early
      detection of caries lesions.
AB  - OBJECTIVE: Sensitivity of a device based on Fluorescence Imaging with Reflectance
      Enhancement (FIRE) in detecting a potential incipient lesion (PIL) was compared
      with visual examination to demonstrate non-inferiority to it. METHODS: Visual
      examination (VE) and an investigational device (ID) were used to detect PIL
      (actual incipient caries [AIC] and hypomineralization). Seventeen subjects
      satisfied data analysis criteria. Two-hundred and seventy-seven AIC and 367
      hypomineralizations reached VE consensus. Ground truth was generated from
      consensus VE results and image information from enhanced white light (eWL) and
      FIRE images. Data from VE and ID in Still Image (IDSM) and Video (IDVM) modes
      were evaluated against ground truth. RESULTS: Overall sensitivity of VE, IDSM,
      and IDVM evaluated against ground truth were 0.94, 0.884, and 0.848,
      respectively, for Actual Incipient Caries (AIC) detection, and 0.95, 0.916, and
      0.883, respectively, for PIL detection. Sensitivity of ID in both modes was > 90%
      that of VE, thus demonstrating non-inferiority of IDSM and IDVM to VE.
      CONCLUSION: The investigated eWL and fluorescence device is clinically effective
      and at least as good as expert VE in detecting PIL. An enhanced white light
      device with FIRE technology can be used, in Video or Still Image Detection modes,
      as an aid to caries diagnosis.

PMID- 24282869
TI  - A new model for demonstrating enamel protection benefits relative to acid
      challenge.
AB  - OBJECTIVE: To determine the applicability of a modified US FDA Caries Monograph
      test method for measuring the protective benefits of fluoride (F) against
      erosive, dietary acids. METHODS: Acid-challenged teeth were treated in two
      studies with a dentifrice, rinsed, and then re-challenged in a series of tests
      using three dietary acids. Study 1 included dentifrices containing 1450 ppm F as
      sodium fluoride (NaF) + triclosan [A], 1450 ppm F (NaF) + potassium nitrate
      (KNO3) [B], 1000 ppm F as sodium monofluorophosphate (SMFP) [C], and 0 ppm F
      (placebo) [D]. Study 2 included dentifrices containing 1450 ppm F (NaF) [A]; and
      0 ppm F (placebo) [B]. Acids were analyzed for phosphate removed during tooth
      challenges, with post-treatment results compared to baseline. Results were
      averaged and reported as a % protection value for each product, with higher
      values indicating greater protection. RESULTS: Study 1: % protection for A =
      16.4; B = 13.0; C = 7.1; and D = -5.2. Study 2: A = 15.2; B = -10.5, with A = B >
      C > D: Study 1; and A > B: Study 2. In each study, p < 0.05, ANOVA. CONCLUSIONS:
      The model provides a viable tool for initially assessing the potential for
      fluoride-containing oral care products to protect teeth against erosive, dietary
      acids. This can then lead to further and more elaborate testing with reasonable
      expectations for outcomes.

PMID- 24282870
TI  - A 12-week clinical comparison of an oscillating-rotating power brush versus a
      marketed sonic brush with self-adjusting technology in reducing plaque and
      gingivitis.
AB  - OBJECTIVE: The aim of this investigation was to assess the comparative gingivitis
      and plaque reduction efficacy of a leading oscillating-rotating power toothbrush
      and a recently introduced sonic toothbrush in adults with gingivitis. METHODS:
      This was a 12-week, randomized and controlled, parallel group, examiner-blind,
      single-center clinical study of 130 adults with pre-existing gingivitis and
      plaque. At baseline, the Modified Gingival Index (MGI), Gingival Bleeding Index
      (GBI), and total number of bleeding sites were assessed, along with plaque levels
      (whole mouth, gingival margin, and interproximal) via the Rustogi Modified Navy
      Plaque Index (RMNPI). Qualified subjects were randomly assigned to one of two
      power toothbrush test groups: the Oral-B Triumph with SmartGuide (marketed in the
      United States as the Oral-B Professional Care SmartSeries 5000 [D34]) oscillating
      rotating brush, or the Colgate ProClinical A1500 (also marketed as elmex
      ProClinical) sonic brush. Subjects brushed at home for two minutes twice daily
      with their assigned power toothbrush and a marketed sodium fluoride dentifrice,
      and were reevaluated for gingivitis at Week 4 and Week 12 via the MGI, GBI, and
      total number of bleeding sites, and for plaque reduction via the RMNPI. RESULTS:
      Ninety-seven percent (97%) of the 130 enrolled subjects completed the trial and
      62 and 65 subjects in the oscillating-rotating and sonic brush groups,
      respectively, had evaluable data for analysis. Statistically significant mean
      reductions in all three gingivitis parameters and plaque relative to baseline
      were seen at both Weeks 4 and 12 with unsupervised use of both test toothbrushes
      (p < 0.001). The oscillating-rotating power brush provided statistically
      significantly superior reductions compared to the sonic brush in mean adjusted
      MGI (31% and 29% at Weeks 4 and 12, respectively; p < 0.001), GBI (17% at Week
      12; p = 0.047), and total number of bleeding sites (48% and 30% at Weeks 4 and
      12, respectively; p = 0.002), and produced statistically significantly greater
      relative mean adjusted plaque reductions for RMNPI whole mouth plaque (38% and
      24% at Weeks 4 and 12, respectively; p < 0.001), gingival margin plaque (36% at
      Week 4; p = 0.004), and interproximal plaque (39% and 26% at Weeks 4 and 12,
      respectively; p < 0.001). Both power toothbrushes were well-tolerated.
      CONCLUSION: An advanced oscillating-rotating power toothbrush produced
      substantial, statistically superior reductions in plaque and gingivitis via
      multiple outcome measures compared to a new sonic toothbrush after both four
      weeks and 12 weeks of tooth brushing.

PMID- 24282871
TI  - Randomized trial of the clinical efficacy of a potassium oxalate-containing
      mouthrinse in rapid relief of dentin sensitivity.
AB  - OBJECTIVE: The aim of this randomized clinical trial was to evaluate the efficacy
      of a mouthrinse containing 1.4% potassium oxalate (Listerine Advanced Defence
      Sensitive; LADS) plus Colgate Cavity Protection Regular toothpaste, in reducing
      dentin sensitivity. METHODS: This was an observer- and examiner-blinded,
      randomized, parallel-group, single-center, controlled, five-day clinical trial.
      Healthy adults were randomized (2:1:1) to LADS plus Colgate Cavity Protection
      Regular toothpaste, or to one of the two negative-control toothpastes alone:
      Crest Cavity Protection Regular or Colgate Cavity Protection Regular. The
      subjects carried out supervised and unsupervised brushing and rinsing twice a
      day. Dentin sensitivity was assessed at baseline and during treatment by Yeaple
      probe (tactile pressure; patient-reported discomfort by visual analogue scale
      [VAS]), as well as response to air blasts (VAS). RESULTS: All sensitivity
      assessments were similar at baseline in the 56 randomized subjects. By the third
      day, the Yeaple probe sensitivity scores for subjects treated with Colgate
      toothpaste plus LADS improved significantly compared to Crest toothpaste alone (p
      < 0.05). By the fifth day, the mean scores for subjects treated with Colgate
      toothpaste plus LADS were significantly improved compared with subjects treated
      with either toothpaste alone (p < 0.05). The other sensitivity assessments showed
      that Colgate toothpaste plus LADS achieved statistically significant improvements
      compared with Colgate and/or Crest toothpaste alone from the third day.
      CONCLUSIONS: The 1.4% potassium oxalate mouthrinse (LADS) was associated with a
      reduction in dentinal sensitivity within a five-day period. Statistically
      significant reductions in all sensitivity variables were achieved by Day 3 and
      even greater reductions in dentin sensitivity scores were observed after five
      days.

PMID- 24282873
TI  - Praying with patients.

PMID- 24282874
TI  - Energy therapies in Christian nursing? Part 2.

PMID- 24282872
TI  - Plaque triclosan concentration and antimicrobial efficacy of a new calcium
      carbonate toothpaste with 0.3% triclosan compared to a marketed 0.3% triclosan
      toothpaste.
AB  - OBJECTIVE: To compare the delivery and retention of triclosan in dental plaque,
      and to compare the antibacterial efficacy of a newly developed toothpaste to a
      marketed calcium carbonate toothpaste. METHODS: Two clinical delivery/retention
      studies were carried out to determine the concentration of triclosan in plaque 10
      minutes, and two and four hours after brushing with a new triclosan-containing
      toothpaste with magnesium aluminium silicate or a marketed triclosan-containing
      toothpaste. Both studies had a double-blind, randomized, complete cross-over
      design. Supragingival plaque samples (minimum 2 microg) were taken from smooth
      surfaces of all teeth (1-7) in all four quadrants for the 10-minute plaque
      measurements and in two randomly allocated quadrants at the two- and four-hour
      time points. Triclosan concentration was measured by HPLC. Antibacterial efficacy
      was evaluated in vitro using a biofilm formation approach. Three replicate
      experiments were carried out to check for repeatability and consistency of the
      assay. Toothpaste slurries were prepared by stirring one part by weight of each
      toothpaste with two parts by weight of deionized water. An overnight culture
      suspension of Streptococcus mutans (ATCC 25175) was prepared and then adjusted to
      give a bacterial count of approximately 10(7) CFU/ml. Sterile HAP discs were used
      as substrate and treated with the toothpaste slurry before inoculation with the
      standardized culture suspension of S. mutans. Following incubation in brain heart
      infusion (BHI) broth containing 2% sucrose for four hours, standard Total Viable
      Count (TVC) procedures were carried out and colonies counted (log10 values).
      RESULTS: Brushing with the new calcium carbonate/triclosan toothpaste resulted in
      a higher triclosan concentration in plaque after 10 minutes, and two and four
      hours compared to a marketed triclosan toothpaste. The increase ranged from 14%
      to 35% and was statistically significant (p < 0.05). The antibacterial efficacy
      of the new calcium carbonate/triclosan toothpaste, measured four hours after
      application, was greater than that of a marketed toothpaste with 0.3% triclosan.
      The difference was statistically significant (p < 0.05). CONCLUSION: The new
      calcium carbonate toothpaste with 0.3% triclosan and magnesium aluminium silicate
      demonstrated significantly greater efficacy four hours post-brushing both in
      terms of in vivo delivery and in vitro antibacterial action compared to a
      marketed calcium carbonate toothpaste with 0.3% triclosan.

PMID- 24282875
TI  - Diagnosing patients.

PMID- 24282876
TI  - The disease of choice.

PMID- 24282877
TI  - Prayer in Clinical Practice: what does evidence support?
AB  - A Korean-born U.S. nurse educator shares a perspective on prayer in clinical
      settings in South Korea and asks what appropriate, ethical prayer practice should
      be in the United States. A review of research on prayer for health and in nursing
      practice is offered, concluding with evidence-based suggestions for prayer with
      and for patients in clinical settings.

PMID- 24282878
TI  - Complementary and alternative therapy use in breast cancer: notable findings.
AB  - Complementary and alternative medicine (CAM) is prevalent among women treated for
      breast cancer but poorly understood in some ethnic groups. This exploratory
      descriptive study characterized CAM use for treatment and general health among
      African and European American women with breast cancer. African American women
      reported higher CAM use and marked emphasis on faith among other differences from
      European American women. Implications for practice are discussed.

PMID- 24282879
TI  - Growing a miracle in Kenya.
AB  - A Kenyan woman, a retired nurse, and a nurse executive in America are
      miraculously led together to start a library in Kima, Kenya. Small beginnings
      grow into the Heather May-MashoodAbiola Children's Resource Centre (HEMAMA).
      Named after two infant children lost by the Kenyan woman and the nurse executive,
      HEMAMA is making a difference in the lives of children in the Kima, Kenya
      community.

PMID- 24282880
TI  - Practicing the Code of Ethics, finding the image of God.
AB  - The Code of Ethics for Nurses gives a professional obligation to practice in a
      compassionate and respectful way that is unaffected by the attributes of the
      patient. This article explores the concept "made in the image of God" and the
      complexities inherent in caring for those perceived as exhibiting distorted
      images of God. While the Code provides a professional standard consistent with a
      biblical worldview, human nature impacts the ability to consistently act
      congruently with the Code. Strategies and nursing interventions that support
      development of practice from a biblical worldview and the Code of Ethics for
      Nurses are presented.

PMID- 24282881
TI  - Develop student compassion through service-learning.
AB  - Compassion is the ability to be sympathetic along with the desire to remedy
      distress and offer help. The art and science of nursing speaks to the need of
      having compassion toward those nurses serve, especially when different from the
      nurse. This article examines the concept of service-learning as a teaching
      strategy and way of developing compassion in today's nursing students.

PMID- 24282882
TI  - Defy Diabetes! A unique partnership with faith community/parish nurses to impact
      diabetes.
AB  - Defy Diabetes! was a two-year grant to Seton Health, Troy, New York, from the New
      York State Health Foundation to impact diabetes in the state. Development of a
      program using the Chronic Care Model to teach Health Living classes in faith
      communities and monitor diabetes management in primary care offices yielded
      positive outcomes. This article reports on Healthy Living class outcomes for
      individuals at risk for or with diabetes and partnership between the Certified
      Diabetes Educators and faith community nurses.

PMID- 24282883
TI  - Defy Diabetes! Impact on faith community/parish nurses teaching Healthy Living
      classes.
AB  - Defy Diabetes! was a 2-year grant to Seton Health, Troy, New York, from the New
      York State Health Foundation to impact diabetes in the state. Development of a
      program using STEP (Spring into Healthy Habits) from St. John Community Health,
      Warren, Michigan, to teach Health Living classes in faith communities and monitor
      diabetes management in primary care offices yielded positive outcomes. This
      article reports the impact on the faith community nurses from participating in
      Defy Diabetes! and teaching Healthy Living classes.

PMID- 24282884
TI  - I how does woundedness--of patients and clinicians--impact spiritual care?

PMID- 24282885
TI  - Nursing at altitude: propelling the profession forward.

PMID- 24282886
TI  - Reflections at retirement: prayer is key!

PMID- 24282888
TI  - Patient safety instead of adversarial medicolegal claims.

PMID- 24282887
TI  - The privilege of caring.

PMID- 24282889
TI  - Duel energy CT imaging of tophaceous gout.

PMID- 24282890
TI  - Entry to medical school--the gender question. What has happened?
AB  - Reform of medical schooI selection has generated concerns that the process
      favours male applicants. The gender profile, HPAT-Ireland and Leaving Certificate
      scores of all applicants in 2009-2011 (n = 9582) and the gender profile of
      entrants from 2008-2011 is presented. Small gender differences favouring males
      are evident in total HPAT-Ireland scores and subsection scores less than 7 and 4
      points respectively with a total selection score impact of approximately 0.8%. In
      relation to Leaving Certificate performance, since 2009, eligible male applicants
      to medicine have tended to outperform females with less than 3 points mean
      difference which has an impact close to 0.7% as selection is still weighted in
      favour of this test. The gender profile of applicants securing a place has varied
      annually. Reforms may have inadvertently altered the gender distribution in
      medical school but there is no evidence that this is entirely attributable to the
      HPAT-Ireland test.

PMID- 24282891
TI  - Antenatal rubella immunity in Ireland.
AB  - The objective of the study was to identify those women attending for antenatal
      care who would have benefited from prepregnancy rubella vaccination. It was a
      population-based observational study of women who delivered a baby weighing < or
      = 500 g in 2009 in the Republic of Ireland. The woman's age, parity, nationality
      and rubella immunity status were analysed using data collected by the National
      Perinatal Reporting System. Of the 74,810 women delivered, the rubella status was
      known in 96.7% (n = 72,333). Of these, 6.4% (n = 4,665) women were not immune.
      Rubella seronegativity was 8.0% (n = 2425) in primiparous women compared with
      5.2% (n = 2239) in multiparous women (p < 0.001), 14.7% (n = 10653) in women < 25
      years old compared with 5.0% (n = 3083) in women < or = 25 years old (p < 0.001),
      and 11.4% (n = 780) in women born outside the 27 European Union (EU27) countries
      compared with 5.9% (n = 3886) in women born inside the EU27 countries (p <
      0.001). Based on our findings we recommend that to prevent Congenital Rubella
      Syndrome, the health services in Ireland should focus on women who are young,
      nulliparous and born outside the EU.

PMID- 24282892
TI  - Venous thromboembolism prophylaxis in acute medical admissions to a university
      teaching hospital.
AB  - The objective of this study was to assess appropriate thromboprophylaxis
      prescription rates in a university hospital and to re-audit after a series of
      interventions. The notes of all acute medical patient admissions over a 4-week
      period were assessed for VTE risk factors and prescription of thromboprophylaxis.
      Subsequently, a series of hospital wide interventions including educational
      initiatives and a new drug prescription chart were introduced. 2 years post
      intervention the audit was repeated. Pre-intervention, 104 of 265 (39%) "at risk"
      patients were prescribed appropriate thromboprophylaxis. Post intervention the
      prescription rate increased to 108 of 188 (57%) "at risk patients". The results
      of the pre- intervention audit are consistent with the published literature.
      While there was a significant increase in prescription rates post intervention,
      over 40% of "at risk" patients still did not receive thromboprophylaxis
      highlighting the challenge in attempting to close the gap between guidelines and
      actual practice.

PMID- 24282893
TI  - Delayed diagnosis of anorectal malformation--a persistent problem.
AB  - Delayed diagnosis of anorectal malformation (ARM) is an avoidable event
      associated with significant complications and morbidity. Previous studies have
      suggested higher than expected rates of delayed diagnosis, especially when a
      threshold of 24 hours of life is used to define delayed diagnosis. The aim of
      this study is to highlight the prevalence of delayed diagnosis of ARM in Ireland
      and to determine if any improvement in rates of delayed diagnosis of ARM has
      occurred since we previously examined this problem over a 10 year period in 2010.
      We compared trends in the incidence of delayed diagnosis of ARM between two
      cohorts, A (1999-2009) and B (2010-2012). Delayed diagnosis was defined as one
      occurring after 48 hours of life. Delayed diagnosis occurred in 29 cases (21.3%)
      in total, with no difference in the incidence of delayed diagnosis between cohort
      A (21 patients [21.2%]) and cohort B (8 patients [21.6%) being recorded. The rate
      of bowel perforation in patients with delayed diagnosis was 10.3% (3 cases). Our
      findings highlight the importance of a careful, comprehensive clinical
      examination in diagnosing ARM and suggest this is still sub-optimal. We strongly
      support the use of a nationally devised algorithm to aid diagnosis of ARM in
      order to avoid life-threatening complications.

PMID- 24282894
TI  - Chinese whispers in the post anaesthesia care unit (PACU).
AB  - We audited verbal handover of information by anaesthetists to recovery room
      nurses based on Situation, Background, Assessment and Recommendation. In Audit A,
      100 handovers for elective procedures were included. For audit B, a second cohort
      of 100 patients was examined post educational session. There was an improvement
      in handover of medical background (46.15% Audit A, 77% Audit B, p < 0.001) and
      allergy status (42% Audit A, 56% Audit B, p = 0.048). Handing over immediate
      postoperative instructions remained unchanged (58% Audit A, 59% Audit B) and
      there was a 4% decline in verbal handover of instructions for ward care. Nurse
      satisfaction with handovers improved by 12%. We conclude that a structured
      process of information transfer, led to improved handover of immediate care.
      Further education focussed on the importance of instructions for the ward to
      maintain continuity of care is recommended.

PMID- 24282895
TI  - Delayed prescribing of antibiotics for respiratory tract infections: use of
      information leaflets.
AB  - The appropriate prescribing of antibiotics is a challenge in primary care12. We
      performed an interventional trial to determine if providing an information
      leaflet on antibiotics with a delayed antibiotic prescription influenced the
      patient's decision to use the antibiotic for a respiratory tract infection (RTI).
      The control group (n = 69) where given a delayed prescription and the
      intervention group (n = 46) were given an information leaflet on antibiotics with
      the delayed prescription. In the control group, 72% (n = 50) of patients
      indicated they subsequently used the antibiotic, and in the intervention group,
      43%(n = 20) indicated they used the antibiotic, this difference was statistically
      significant (p = 0.0018.) The key conclusion of this study is that delayed
      prescriptions should be issued with an appropriate information sheet.

PMID- 24282896
TI  - Hip pain and cauda equina syndrome.
AB  - Acute cauda equina syndrome secondary to a spinal epidural abscess as a result of
      a psoas abscess is very uncommon. We report the case of a 64-year old with a 6
      day history of left hip pain, which progressively worsened until she presented to
      the emergency department with systemic infective symptoms and classical acute
      cauda equina syndrome. A good clinical outcome was achieved by urgent posterior
      decompression, followed by CT-guided drainage of the psoas abscess and
      appropriate antibiotic treatment.

PMID- 24282897
TI  - Uterine sarcoma after tamoxifen therapy for breast cancer.
AB  - Tamoxifen has been shown to significantly reduce the risk of tumour recurrence in
      women with receptor positive breast cancer and has been used for chemoprevention
      in women with both non-invasive cancer and those with a high risk of developing
      breast cancer. An established and accepted risk with this treatment is the
      increased incidence of adenocarcinoma of the endometrium. Less well recognised is
      uterine sarcoma, a rare and aggressive tumour accounting for under five percent
      of uterine malignancies, with five year survival rates in the order of 50%.

PMID- 24282898
TI  - Case 3: aspergilloma.

PMID- 24282899
TI  - Higher specialist training in paediatrics 2005-2010, the graduates' reflections.
AB  - This study of paediatric trainees, who were awarded their CSCST from 2005 to
      2010, evaluated their training experience and assessed whether the curriculum
      goals were achieved. From an incomplete database 23 (57.7%) graduates based in
      Ireland and 3 (19%) based abroad responded. Twenty one (81%) of respondents were
      currently working in Ireland as consultants, 20 (80%) had a post membership
      qualification and 23 (92%) had travelled abroad for fellowships. Positive
      experiences included clinical training (44%), positive role models (44%), quality
      of the training days (52%).Negative experiences included lack of protected time
      for research (52%), excessive clinical service (28%), and poor monitoring of
      trainers (20%). Mean Likert scores for curriculum competencies were clinical care
      4.9, clinical knowledge 5, application of evidence 3.7, academic supervisor
      skills3.3, knowledge of public health 3.2, health economics 2.2, and healthcare
      systems modification 2.3. The curriculum deficiencies can be addressed through
      the diploma in Leadership and Quality in Healthcare which has been developed by
      the Health Service Executive and the College of Physicians but an adequate
      database of graduates needs to be maintained.

PMID- 24282900
TI  - Pulmonary sequelae of severe H1N1 infection treated with high frequency
      oscillatory ventilation.
AB  - During the recent influenza A (H1N1) pandemic, due to severe respiratory failure
      many patients required treatment with alternative ventilator modalities including
      High Frequency Oscillatory Ventilation (HFOV). We present four such patients
      treated with HFOV at an academic, tertiary referral hospital in Ireland. We
      detail outcomes of clinical examination, pulmonary function testing, quality of
      life assessment and radiographic appearance on CT Thorax at follow-up at 6
      months. Further clinical assessment and pulmonary function testing were performed
      at median 19 months (range 18-21 months) post-discharge. At initial review all
      patients were found to have reduced gas transfer (median predicted DLCO 74%) with
      preservation of lung volumes and normal spirometrical values at 6 months (median
      FVC 5.42L [101% predicted] and FEV14.5L [101.2% predicted] respectively), with
      improvements in gas transfer (median predicted DLCO 83%)at subsequent testing.
      Post-inflammatory changes on CT thorax at 6 months were seen in all 4 cases. To
      our knowledge this is the first report to document the long-term effects of
      severe H1N1 infection requiring high frequency oscillation on respiratory
      function. We conclude that the effects on respiratory function and pulmonary
      radiological appearance are similar to those observed following conventional
      treatment of Acute Respiratory Distress Syndrome [ARDS].

PMID- 24282901
TI  - Economics and ethics of paediatric respiratory extra corporeal life support.
AB  - Extra corporeal membrane oxygenation (ECMO) is a form of life support, which
      facilitates gas exchange outside the body via an oxygenator and a centrifugal
      pumping system. A paediatric cardiac ECMO programme was established in 2005 at
      Our Lady's Children's Hospital, Crumlin (OLCHC) and to date 75 patients have
      received ECMO, the majority being post operative cardiac patients. The outcome
      data compares favourably with international figures. ECMO has been most
      successful in the treatment of newborn infants with life threatening respiratory
      failure from conditions such as meconium aspiration, respiratory distress
      syndrome and respiratory infections. There is no formal paediatric respiratory
      ECMO programme at OLCHC, or anywhere else in Ireland. Currently, neonates
      requiring respiratory ECMO are transferred to centres in Sweden or the UK at an
      average cost of 133,000 Euros/infant, funded by the Health Service Executive E112
      treatment abroad scheme. There is considerable morbidity associated with the
      transfer of critically ill infants, as well as significant psycho-social impact
      on families. OLCHC is not funded to provide respiratory ECMO, although the
      equipment and expertise required are similar to cardiac ECMO and are currently in
      place. The average cost of an ECMO run at OLCHC is 65,000 Euros. There is now a
      strong argument for a fully funded single national cardiac and respiratory
      paediatric ECMO centre, similar to that for adult patients.

PMID- 24282902
TI  - Can lithium unmask the preclinical Parkinsonian features?

PMID- 24282903
TI  - Metastatic ovarian tumors: a clinicopathologic study of 150 cases.
AB  - OBJECTIVE: To determine the frequency of metastatic ovarian tumors and to
      identify their clinicopathologic features. STUDY DESIGN: A total of 150 patients
      with pathologically confirmed metastatic ovarian carcinoma who were treated
      between 1995 and 2011 at the Mexican Oncology Hospital were identified by
      retrospective review. Clinicopathologic data were analyzed. RESULTS: Metastatic
      ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary
      sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix
      (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%).
      Gynecologic primary sites were the uterine cervix (4%) and the uterine body
      (23%). Primary malignancies were detected first in 66 patients (44%) and
      simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass
      was the first manifestation of disease in 20.6% of the cases. The patients ranged
      in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35
      patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid
      cystic in 38, and multicystic in 44. CONCLUSION: Metastatic ovarian carcinomas
      are an important group of ovarian neoplasms, constituting 15.7% of all ovarian
      malignancies. Most of them arise from the gastrointestinal tract.

PMID- 24282904
TI  - Expression of NFkappaB, ICAM1, and VCAM1 in rheumatic heart disease with atrial
      fibrillation.
AB  - OBJECTIVE: To examine the expression of nuclear factor kappaB (NFkappaB),
      intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1
      (VCAM1) levels in rheumatic heart disease patients who suffer from atrial
      fibrillation and those who do not. STUDY DESIGN: Twenty-six patients with
      rheumatic heart disease were enrolled. Ten patients had no history of atrial
      fibrillation and 16 had atrial fibrillation. Atrial tissue was obtained from the
      right atrial appendage during heart surgery. The expression levels of NFkappaB,
      ICAM1, and VCAM1 were examined with immunohistochemical staining. RESULTS:
      Myocardial inflammation and fibrosis were both increased in patients with atrial
      fibrillation. The levels of NFkappaB, ICAM1, and VCAM1 were significantly
      elevated in patients with atrial fibrillation as compared with the control group
      (all p < 0.05). CONCLUSION: Overexpression of NFkappaB, ICAM1, and VCAM1 may be
      involved in the development and maintenance of atrial fibrillation in patients
      with rheumatic heart disease.

PMID- 24282905
TI  - Effects of pulsed and sinusoidal electromagnetic fields on MMP-2, MMP-9, collagen
      type IV and E-cadherin expression levels in the rat kidney: an
      immunohistochemical study.
AB  - OBJECTIVE: To investigate the role of extremely low frequency pulsed and
      sinusoidal electromagnetic fields on kidney tissues. STUDY DESIGN: Twenty-seven
      male Wistar albino rats were used. The rats were divided into 3 groups (n = 9):
      control group, sinusoidal electromagnetic field (SEMF) group, and pulsed
      electromagnetic field (PEMF) group. The SEMF and PEMF groups (pulse time 25
      microsn, pulse frequency 50 Hz) were subjected to 1.5 mT, 50 Hz, exposure 6 hours
      a day, 5 days a week for 28 days in methacrylate boxes. Formalin-fixed, paraffin
      embedded kidney tissue sections were stained with hematoxylin-eosin, Gomori and
      periodic acid-Schiff. In addition, matrix metalloproteinase-2 (MMP-2) and 9 (MMP
      9), E-cadherin and collagen type IV expression levels were examined
      immunohistochemically. RESULTS: Thickening of glomerular basement membranes was
      evident in electromagnetic fields, especially in the SEMF group. In addition,
      expression levels of E-cadherin were decreased with electromagnetic field (EMF)
      exposure. The expression level of MMP-9 increased, and MMP-2 and collagen type IV
      expression levels were not altered with EMF exposure. CONCLUSION: Both EMFs
      changed the molecular component of the kidney adversely.

PMID- 24282906
TI  - Computer-based image analysis system designed to differentiate between low-grade
      and high-grade laryngeal cancer cases.
AB  - OBJECTIVE: To design a pattern recognition (PR) system for discriminating between
      low- and high-grade laryngeal cancer cases, employing immunohistochemically
      stained, for p63 expression, histopathology images. STUDY DESIGN: The PR system
      was designed to assist in the physician's diagnosis for improving patient
      survival. The material comprised 55 verified cases of laryngeal cancer, 21 of low
      grade and 34 of high-grade malignancy. Histopathology images were first processed
      for automatically segmenting p63 expressed nuclei. Fifty-two features were next
      extracted from the segmented nuclei, concerning nuclei texture, shape, and
      physical topology in the image. Those features and the Probabilistic Neural
      Network classifier were used to design the PR system on the multiprocessors of
      the Nvidia 580 GTX graphics processing unit (GPU) card using the Compute Unified
      Device Architecture parallel programming model and C++ programming language.
      RESULTS: PR system performance in classifying laryngeal cancer cases as low grade
      and high grade was 85.7% and 94.1%, respectively. The system's overall accuracy
      was 90.9%, using 7 features, and its estimated accuracy to "unseen" by the system
      cases was 80%. CONCLUSION: Optimum system design was feasible after employing
      parallel processing techniques and GPU technology. The proposed system was
      structured so as to function in a clinical environment, as a research tool, and
      with the capability of being redesigned on site when new verified cases are added
      to its repository.

PMID- 24282907
TI  - Morphometric evaluation of AgNORs in odontogenic cysts.
AB  - OBJECTIVE: To evaluate the morphometry of AgNORs in odontogenic cysts and to
      compare their biologic behavior to determine whether AgNOR morphometry is helpful
      in predicting the behavior. STUDY DESIGN: Ten cases each of odontogenic
      keratocyst (OKC), dentigerous cyst (DC) and radicular cyst (RC) were stained with
      silver nitrate. Morphometric analysis of 100 selected epithelial and connective
      tissue cells was done to record their nuclear volume, nuclear perimeter, contour
      index of the nucleus, AgNOR count, AgNOR proportion and single AgNOR volume. The
      results were statistically analyzed using ANOVA. RESULTS: AgNOR count, nuclear
      volume and nuclear perimeter were greatest in the OKC followed by DC and RC,
      suggesting that these parameters differentiate between the aggressive and less
      aggressive odontogenic cysts. Single AgNOR volume and AgNOR proportion were
      greatest in the RC followed by OKC and DC, respectively. CONCLUSION: Results of
      our study taken in isolation point to AgNOR count as the most reliable factor in
      differentiating between aggressive and nonaggressive odontogenic cysts.

PMID- 24282908
TI  - Morphology of the oviduct of commercial egg-laying hens supplemented with organic
      minerals.
AB  - OBJECTIVE: To analyze the morphology of the oviduct of commercial egg-laying hens
      supplemented with organic minerals. STUDY DESIGN: A total of 2,400 Dekalb hens at
      42 weeks of age were included in the study. Throughout the period of the
      experiment (10 months, divided into 4 periods of 10 weeks each) a supplement was
      administered. The animals were divided at random into 2 groups, each consisting
      of 1,200 hens: Group I, the control group of hens that did not receive the
      supplement, and Group II, the group of hens that were administered the
      supplement. The morphology of the oviduct was evaluated; all tests were performed
      from 52 to 82 weeks. After the hens were sacrificed by cervical dislocation,
      fragments of the oviduct were collected, 10 hens per group, which were fixed in
      Bouin liquid for 6 hours. Then they were processed and analyzed for light
      microscopy. RESULTS: Analyzing the hens' oviduct, there was no change in weight
      of organs, but microscopy revealed that the hens' oviduct epithelium in Group II
      was preserved, with uniform cilia. CONCLUSION: Based on our results we can
      conclude that the organic mineral supplementation causes an improvement in hens'
      oviduct morphology.

PMID- 24282909
TI  - Human placental macrophages (Hofbauer cells) in severe preeclampsia complicated
      by HELLP syndrome: immunohistochemistry of chorionic villi.
AB  - OBJECTIVE: To evaluate Hofbauer cells in the placentas of women diagnosed with
      HELLP syndrome. STUDY DESIGN: The present study compared 20 patients with HELLP
      syndrome and 20 control patients with respect to demographics, hematological
      parameters and the presence of Hofbauer cells in placental samples. CD-68
      antibody was used for immunohistochemical examination. The total number and size
      of Hofbauer cells were measured in the placental villi, and the proportion of
      Hofbauer cells relative to the vascular structure was also compared between
      groups. RESULT: The patient and control groups were similar according to baseline
      obstetric characteristics. White blood cell counts in patients with HELLP
      syndrome and the control group were 15,139 +/- 4,169 and 10,806 +/- 2,888,
      respectively, and were significantly increased among patients with HELLP syndrome
      (p < 0.001). Hofbauer cell numbers in the placental villi of patients with HELLP
      syndrome were significantly elevated in comparison to normotensive controls (p =
      0.046). The proportion of Hofbauer cells in the placental villi according to
      proximity to the vascular structure were 3.85 +/- 1.66 in the HELLP group and
      1.75 +/- 1.12 in controls (p < 0.001). Sizes of the Hofbauer cells were not
      statistically different between groups. CONCLUSION: Increased Hofbauer cells may
      be associated with increased inflammation or may have an adaptive mechanism at
      the fetal site of the placenta in patients with HELLP syndrome.

PMID- 24282910
TI  - Granular cell tumor of the bladder: a case report.
AB  - BACKGROUND: Granular cell tumor is usually a benign tumor, generally believed to
      be of neural origin, most commonly affecting the tongue and skin. Although it can
      present in any part of the body, the bladder is a rare location, with only 16
      cases found in the English-language literature. CASE: We report the case of a 54
      year-old woman with hematuria who had a solid tumor in the posterior wall of the
      bladder. Histological study of the samples obtained by transurethral resection
      revealed a granular cell tumor, confirmed by immunohistochemical techniques.
      CONCLUSION: Granular cell tumors of the bladder are rare and generally benign but
      frequently present macroscopic features resembling those of urothelial carcinoma.
      The similarity can lead to an erroneous clinical diagnosis and unnecessary,
      aggressive treatment. A careful histopathological assessment is essential for an
      accurate diagnosis.

PMID- 24282911
TI  - Urinary bladder melanosis associated with urothelial dysplasia and invasive
      urothelial carcinoma: a report of two cases.
AB  - BACKGROUND: Melanosis is defined as an abnormal or excessive deposition of
      melanin within cells and/or tissues. It typically presents as a cutaneous or
      buccal mucosal lesion, but rare cases of bladder melanosis have also been
      documented. Melanosis of the urinary bladder is typically considered a benign
      condition, but it has also been described in association with malignant melanoma
      and urothelial carcinoma. CASES: We report the cases of 2 patients who presented
      with melanosis of the urinary bladder. One patient presented with melanosis of
      the urinary bladder together with urothelial dysplasia. Melanosis was
      incidentally identified during a cystoscopy for ureteral stones. A second patient
      presented with hematuria and was found to have a muscle invasive urothelial
      carcinoma with focal small nested morphology together with melanosis. We also
      present a literature review of the bladder melanosis and an overview of other
      bladder melanocytic lesions, which include primary and metastatic melanoma and
      blue nevus. CONCLUSION: Initial evaluation for bladder melanosis should include
      cystoscopy and upper urinary tract imaging. Biopsy is essential to establish the
      diagnosis and rule out associated malignancy.

PMID- 24282912
TI  - [Sanitation infrastructure and health].

PMID- 24282913
TI  - Breast asymmetry pattern in women with idiopathic scoliosis.
AB  - Breast asymmetry is frequent in women with idiopathic scoliosis. To understand
      the pattern of breast asymmetry in these women a clinical study was performed in
      which 54 female patients with idiopathic scoliosis were evaluated. The
      information recorded for each patient included: age, weight, height, scoliosis
      type, Cobb angle, breast measurements, and presence of rib cage asymmetry. Breast
      volume was calculated using anatomic measurements (anthropomorphic method). The
      mean age of the group was 25 +/- 7 years. A right convex thoracic curve occurred
      in 85%, with a mean Cobb angle of 32 +/- 15 degrees. Our study indicated that
      women with idiopathic scoliosis consistently presented breast asymmetry that
      followed a predictable pattern. The breast on the side of the convex thoracic
      scoliosis curve is always smaller in volume (mean difference 59 +/- 39 mi). The
      affected side also presents a smaller areola, a higher position of the nipple
      (mean difference 2.2 +/- 1.3 cm) and a higher position of the inframammary fold
      (mean difference 2.1 +/- 1.4 cm) when compared to the opposite breast. Though the
      asymmetry is predictable, the degree to which the patient presents these changes
      does not correlate with the severity of the scoliosis (Cobb angle). We believe
      that the severity of the asymmetry is a result of the difference between the
      hypoplastic breast and the normal breasts. In women with very large opposite
      breasts the asymmetry appears to be worse.

PMID- 24282914
TI  - Pregnancy outcomes and successful rate of nifedipine therapeutic protocol
      implementation in a hospital of San Juan.
AB  - PRIMARY OBJECTIVE: evaluation of Nifedipine protocol success defined as
      postponement of labor for 48 hours. SECONDARY OBJECTIVE: evaluation of the
      presence of risk factors in patients that develop preterm labor and delivery
      outcome. MATERIALS AND METHODS: Chart review retrospective study with patients
      admitted to the Hospital of the Metropolitan Area of San Juan in the period of
      January 1,2009 to December 31, 2010 with diagnosis of preterm labor. A total of
      382 patient's records were evaluated for inclusion and exclusion criteria. 48 met
      all the requirements to be included in the study. RESULTS: There were 68.8%
      patients who successfully completed the 48 hours postponement of labor required
      to administer corticosteroid therapy for fetal lung maturation. Risk factors for
      preterm labor commonly observed in the study group were urinary tract infection
      (60.4%), previous preterm labor (43.8%), multiple gestations (12.5%), and preterm
      premature rupture of membranes (10.4%). DISCUSSION: The use of Nifedipine therapy
      in patients with preterm labor between 24-34 weeks of gestational age can be
      effective in the postponement of labor for 48 hours so that the patient can
      receive corticosteroid fetal lung maturation therapy. The most common risk factor
      observed in this group of patients with preterm labor was urinary tract
      infection.

PMID- 24282915
TI  - Magnesium: the forgotten electrolyte.
AB  - Magnesium (Mg++), Potassium (K+) and Calcium (CA++) are important electrolytes in
      keeping a stable electrical status. The purpose of this study was to measure them
      in critically ill patients. METHODS: We evaluated the electrolytes in 28
      consecutive patients. Eighteen were females and 10 males with mean age of 62 +/-
      5 years. RESULTS: The admission diagnosis in 95% of the cases was congestive
      heart failure. Sixty-four percent of the patients had subnormal values of Mg++,
      53% subnormal values of K+, and 28% subnormal values of CA++. Fourteen percent
      showed lower values of the three electrolytes and 35% only of Mg++ and K+
      concomitantly. Twenty-eight percent showed prolonged QTC interval. All patients
      with prolonged QTC interval had low Mg++ and K+ levels. Twenty five percent of
      the patients showed atrial fibrillation, 25% ventricular tachycardia, and 3%
      junctional tachycardia. The ventricular tachycardia group had more electrolyte
      abnormalities than those with atrial fibrillation. None of the patients received
      Mg++ replacement during critical management while 50% received K+ replacement.
      CONCLUSION: This data shows physician overlook the Importance of Mg++ and K+
      deficiency in critically ill patients.

PMID- 24282916
TI  - Comparison of the appropriate use of antibiotics based on clinical guidelines
      between physicians in-training versus practicing physicians.
AB  - The inappropriate antibiotic can lead to serious negative effects on health. This
      has been the cause of emergence of multidrug resistant bacteria and the need of
      surveillance of antibiotics in the inpatient setting. An adequate knowledge on
      which and when prescribing antibiotics is essential to avoid these issues.
      Because of this problems, guidelines have been developed to educate and control
      the misuse and abuse of antibiotics and improve clinical outcomes. We evaluated
      the medical knowledge, medical trends, and the effectiveness of professional
      interventions among Puerto Rico physicians in promoting prudent antibiotic
      prescribing. A comparative study was performed using a questionnaire about
      prudent antibiotic use in common infections seen in Puerto Rico. It was
      distributed among the major three internal medicine training programs at San
      Juan, internal medicine physicians and general physicians. General physicians
      failed to treat adequately asymptomatic bacteriuria, and overall failed in
      treating other common conditions when compared with residents and internal
      medicine physicians. One of our questions was related to the treatment of
      Extended Spectrum Beta Lactamase (ESBL) positive Escherichia coli (E. coli) and
      more than 50% of the surveyed failed to answer the question correctly. Conditions
      as viral respiratory tract infections and community acquired pneumonia had the
      higher correctly answered questions among the groups. Our questionnaire
      demonstrates that guidelines have to reach the education among the general
      physician population to decrease the overuse of inadequate antibiotics, and
      education should be strengthen on those internal medicine physicians that have
      already completed formal training.

PMID- 24282917
TI  - Pregnancy and neonatal outcomes of women receiving compounded 17-alpha
      hydroxyprogesterone at San Juan City hospital.
AB  - OBJECTIVE: To describe the pregnancy and neonatal outcomes of women receiving
      17alpha-hydroxyprogesterone to prevent subsequent preterm birth in our
      institution. METHODS: Forty-two patient received treatment by VITA healthcare and
      their charts were reviewed for results and outcomes. RESULTS: An increase in
      average gestational age at the time of delivery was noticed as well as an
      increase in weeks gained compared to previous preterm birth. DISCUSSION: More
      than 75% of the patients prolonged their pregnancy with the use of 17alpha
      hydroxyprogesterone. Continuation of the study and stratifying patients will help
      in identifying other risk factors and establishing criteria for improved
      prevention of preterm birth and prognosis.

PMID- 24282918
TI  - Profile of patients admitted with infected skin ulcers at Bella Vista Hospital
      Mayaguez.
AB  - The purpose of this study is to evaluate the characteristics of patients admitted
      to Bella Vista Hospital in Mayaguez with a diagnosis of infected skin ulcer, the
      most common microorganisms recovered in cultures, and their antimicrobial
      sensitivity patterns. METHODS: All patients discharged with the diagnosis of
      infected skin ulcer from January 1 through December 31, 2012 were selected.
      Following variables were extracted: sex, age, hospital stay, morbid conditions,
      antibiotics used, microorganisms identified on cultures and sensitivity of
      microorganisms to different antimicrobials. Prevalence rates were estimated for
      different conditions and different microorganisms. The use of empirical
      antibiotics were described and compared with the antimicrobial sensitivity of the
      microorganisms. RESULTS: The study population consisted of 98 subjects (54%
      female, 46% male). Mean age was 71 years old, with 71% of subjects older than 65
      years old. Prevalence rates of diabetes mellitus, peripheral vascular disease,
      hypertension and osteomyelitis were 74.5%, 74.5%, 79.6%, and 17.5% respectively.
      The antibiotic most frequently used was piperacyllin-tazobactam (PTZ). The
      organisms most frequently found on cultures were Staphylococcus (37.8%),
      distributed as 20.4% methicillin resistant and 17.3 sensitive to methicillin,
      followed by E. coli (30.6%), Streptococcus (29.6%), and Pseudomonas (27.6%). The
      majority of microorganisms were sensitive to PTZ. There was a higher prevalence
      of osteomyelitis in diabetic patients than in non-diabetic patients but the
      difference was not statistically significant. CONCLUSIONS: Antibiotic sensitivity
      patterns were consistent with the expected, according to the literature.
      Empirically used antibiotics were appropriate according to sensitivity patterns
      shown in the study.

PMID- 24282919
TI  - [Creation and validation of the scale for measuring quality of life in patients
      with cancer: Puerto Rican version (ECVCA-PR). ].
AB  - The aim of this pioneer study is to begin to create and validate a scale to
      measure Quality of Life in cancer patients in Puerto Rico (ECVCA-PR) in order to
      provide local health professionals with a reliable instrument that help to
      measure attitudes that could affect different patient's quality of life aspects
      and allows knowing the needs of those cancer patients. Sample consisted of 32
      patients (9 men, 23 women), between ages of 30 to 83 years that were receiving
      services (i.e., hospitalization, treatment, and follow up) at Dr. Isaac Gonzalez
      Martinez Oncological Hospital in San Juan, Puerto Rico. The psychometric
      properties of the instrument indicate a reliability index (Cronbach's Alpha) of
      0.927 with 164 items, an excellent index according to the literature.

PMID- 24282920
TI  - Exacerbation of mood symptoms associated to primary and secondary carnitine
      deficiency: a case report.
AB  - Rarely screened in psychiatric patients, primary and/or secondary Carnitine
      deficiency could be influencing and/or mimicking the mood symptoms of our patient
      population. The brain and specifically neurons are highly vulnerable to
      impairments in oxidative metabolism, which can lead to neuronal cell death and
      disorders of neurotransmitters causing changes in cognition and behavior. For
      this reason, identification of this disorder is important since its treatment
      could result in symptom improvement and better quality of life of our patients.
      We present a case where exacerbation of mood symptoms was associated to primary
      and secondary Carnitine deficiency.

PMID- 24282921
TI  - Rectovestibular fistula with normal anus: a treatment alternative.
AB  - Congenital rectovestibular fistulas with normal anus are a rare form of anorectal
      malformations, especially in the Western hemisphere. Due to its rarity, consensus
      on preoperative management, surgical technique and postoperative care is still in
      debate. We describe a specific case with its management plan and outcomes while
      providing an up to date literature review on current management trends.

PMID- 24282922
TI  - An unexpected side-effect of a commonly used drug.
AB  - We report a case of a 68 year-old-female patient with clinical features of drug
      induced lupus erythematosus after five years of treatment with amiodarone. She
      presented generalized skin rash, arthralgia on upper and lower extremities,
      associated with difficulty to walk. Remarkable laboratory results revealed a
      positive antinuclear antibody test and a skin rash biopsy showing a superficial
      and deep perivascular infiltrate of lymphocytes, histiocytes, and eosinophils.
      Once the etiology of the patient's symptoms was identified, the culprit drug was
      removed and she had a complete remission of all signs and symptoms. Early
      diagnose should be recognized for prompt intervention and avoid further
      complications associated with this rare side-effect.

PMID- 24282923
TI  - Menstrual psychosis: presenting symptom of bipolar disorder not otherwise
      specified in a 13-years-old Hispanic female.
AB  - Exacerbation of symptoms in mood disorders such as bipolar disorders, major
      depressive disorders and premenstrual dysphoric disorders could be influenced by
      the hormonal changes of the menstrual cycles in female patients. Menarche has
      been related to onset of mood symptoms, which at times have been described as
      menstrual psychoses and could represent an early presentation of Pediatric
      bipolar disorders. Pediatric bipolar disorders appear to be characterized by less
      clearly defined mood episodes, shorter duration of these episodes, and different
      hallmark symptoms than in adults. This report describes a pediatric patient who
      had no previous psychiatric symptoms and for whom menstrual psychosis was the
      presenting symptom of bipolar disorder not otherwise specified.

PMID- 24282924
TI  - Ethnicity and genetics are more important than diabetes mellitus and hypertension
      in producing cardiovascular events in patients with the metabolic syndrome:
      emphasis in the Puerto Rico population.
AB  - Metabolic syndrome is a cluster of risk factors for cardiovascular disease that
      affects an estimated 50 million Americans. The present article reviews the
      metabolic syndrome with respect to its definition, epidemiology, pathophysiology
      and management. A primary focus in research has been to elucidate the processes
      determined to cause insulin resistance, the fundamental mechanism underlying the
      metabolic syndrome. Namely, the incidence, component characteristics and
      complications of the metabolic syndrome in the island of Puerto Rico are
      described alongside the fact that the metabolic syndrome may be milder in Puerto
      Rico than in the mainland United States because it is characterized by less
      aggressive coronary disease and a relatively normal lipid profile. This suggests
      that the cardiovascular complications are more influenced by genetics and culture
      than diabetes mellitus and hypertension.

PMID- 24282925
TI  - Pulmonary lymphangioleiomyomatosis: literature update.
AB  - Pulmonary lymphangioleiomyomatosis is an uncommon disease of unknown etiology
      characterized by the proliferation of abnormal smooth muscle cells in the lungs,
      leading to parenchymal destruction and progressive respiratory failure. The
      natural history of this disease remains poorly understood, primarily seen in
      women of childbearing age. The diagnosis can be difficult because symptoms are
      nonspecific and very similar to other respiratory diseases like asthma, emphysema
      and bronchitis. Lymphangioleiomyomatosis may not be diagnosed until a
      pneumothorax, chylothorax, interstitial lung disease or angiomyolipomas are
      discovered. The recent advances in genetic and molecular research provide new
      hope to discover the intricate mechanism of disease and evaluate new therapies.
      Internists, primary care physicians and pulmonologists should be aware of this
      condition in order to avoid delay in the diagnosis and institute appropriate
      therapy. The clinical features, pathophysiology, molecular genetics and medical
      treatment will be reviewed.

PMID- 24282926
TI  - [Anatomic variations of the internal carotid artery: implications for the
      neurologic endovascular therapist].
AB  - Tortuosity of the cervical segment of the internal carotid artery (ICA) can
      hinder navigation intravascular devices for treating intracranial aneurysms and
      even complex ICA access techniques can fail. Variations in the course of the
      internal carotid artery are known as coiling, kinking or tortuosity of the
      vessel. Such failures have clinical relevance. During endovascular procedures
      these anomalies difficult the intravascular surgical procedure. A potential
      alternative is the reconstruction of these anatomic anomalies of the carotid
      artery using neuro-interventional methods. We present a practical review of the
      literature.

PMID- 24282927
TI  - Determination of isoflavone content in soy, red clover, and kudzu dietary
      supplement materials by liquid chromatography-particle beam/electron ionization
      mass spectrometry.
AB  - Increased consumption of dietary supplements brings about important requirements
      of analytical methods to allow accurate and precise measurements of the chemical
      composition of these botanical materials. Presented here is the isoflavone
      content in proposed National Institute of Standards and Technology standard
      reference materials (SRMs) determined by LC-particle beam/electron ionization MS.
      Botanical materials (soy, red clover, and kudzu) are characterized for the
      content of a suite of five isoflavones (puerarin, daidzein, genistein,
      formononetin, and biochanin A). These compounds are of interest due to
      correlations with certain health benefits. An RP chromatographic separation was
      first optimized using UV-Vis spectrophotometric detection. The LC output was then
      introduced to an electron ionization source using a particle beam interface on an
      Extrel Benchmark MS system. The separation was carried out using a commercial C18
      column and a linear gradient using water and methanol (both containing 0.1%
      trifluoroacetic acid as mobile phases A and B, at a flow rate of 1.0 mL/min over
      40 min. LOD values for the isoflavones were determined to be at the ng level.
      Quantitation was performed using an internal standard (IS) approach with 7
      hydroxy-4-chromone as the IS compound. The levels of isoflavones in the botanical
      products were determined for the proposed SRMs.

PMID- 24282928
TI  - Determination of catechins and caffeine in camillia sinensis raw materials,
      extracts, and dietary supplements by HPLC-uv: single-laboratory validation.
AB  - A rapid method has been developed to quantify seven catechins and caffeine in
      green tea (Camillia sinensis) raw material and powdered extract, and dietary
      supplements containing green tea extract. The method utilizes RP HPLC with a
      phenyl-based stationary phase and gradient elution. Detection is by UV
      absorbance. The total run time, including column re-equilibration, is 13 min.
      Single-laboratory validation (SLV) has been performed on the method to determine
      the repeatability, accuracy, selectivity, LOD, LOQ, ruggedness, and linearity for
      (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, (-)
      gallocatechin gallate, (-)-epigallocatechin gallate, and (+)-gallocatechin, as
      well as caffeine. Repeatability precision and recovery results met AOAC
      guidelines for SLV studies for all catechins and caffeine down to a level of
      approximately 20 mg/g. Finished products containing high concentrations of
      minerals require the use of EDTA to prevent decomposition of the catechins.

PMID- 24282929
TI  - Simultaneous determination of 12 coumarins in bamboo leaves by HPLC.
AB  - A simple, rapid, and sensitive HPLC-UV method was developed for qualitative and
      quantitative analysis of 12 coumarin compounds (skimin, scopolin, scopoletin,
      umbelliferone, 6,7-dimethoxycoumarin, coumarin, psoralen, xanthotoxin, 5,7
      dimethoxycoumarin, pimpinellin, imperatorin, and osthole) in bamboo leaves. The
      samples were extracted with ethanol-water (70 + 30, v/v) by ultrasonication and
      purified by Florisil SPE. The method was validated for linearity, LOD, LOQ,
      accuracy, precision, and recovery. The standard curves in the corresponding
      ranges had good linearity. LOD was at the range of 0.19 to 0.85 mglkg and LOQ
      0.64 to 2.82 mg/kg. The values of RSD for accuracy and intraday and interday
      precision were less than 3%, except for 6,7-dimethoxycoumarin. Recoveries from
      spiked samples at 30, 20, and 10 mg/kg in Dendrocalamus giganteus Munro were
      higher than 70%, except for scopoletin, 6,7-dimethoxycoumarin, and coumarin. The
      method was validated using field-collected samples taken from Beijing and
      Changning Counties, SiChuan, China. Six coumarins, namely, skimin, scopolin,
      scopoletin, umbelliferone, coumarin, and pimpinellin, were found in the extracts
      of 11 species of bamboo leaves. The concentrations of total coumarins were in the
      range of 8.67 to 99.2 mg/kg. The maximum concentration of total coumarins was
      found in Bambusa pervariabilis, and the minimum was in

PMID- 24282930
TI  - Modified AOAC three step method (officialmethod 2008.05): consolidation of
      fractions B and C.
AB  - The AOAC Quantitative Three Step Method (TSM; AOAC Official Method SM 2008.05) is
      validated for testing the efficacy of liquid sporicides against spores of
      Bacillus subtilis and Bacillus anthracis on selected hard, nonporous, and porous
      surfaces. The TSM uses 5x5x1 mm inoculated coupons (carriers), which are placed
      in 400 microL liquid sporicidal agent contained in a microcentrifuge tube.
      Following exposure of inoculated carriers to the test chemical and subsequent
      neutralization, viable spores are recovered in three fractions: A (gentle
      tapping), B (sonication), and C (gentle agitation). The spores in suspension are
      serially diluted and plated on a recovery medium for enumeration. The plate
      counts are summed over the three fractions to provide the number of viable spores
      per carrier, which is log10-transformed to generate a mean log density (LD) value
      across carriers. As a measure of product efficacy, a log reduction (LR) value is
      calculated by subtracting the mean LD for treated carriers from the mean LD for
      control carriers. This paper reports on the comparative evaluation of the current
      and modified versions of the TSM in order to support a modification to simplify
      the procedure. The proposed modified TSM (mTSM) consolidates fractions B and C in
      the same tube. Thus, the sonication (fraction B) and gentle agitation (fraction
      C) steps are carried out in the same tube, thereby reducing the number of tubes
      and associated resources and time necessary to complete the test. Glass, steel,
      pine wood, and ceramic tile carriers were included in the comparative study.
      Inoculated carriers were evaluated against two preparations of sodium
      hypochlorite to generate two presumed levels of efficacy (intermediate and high);
      the control LD and LR values associated with testing each carrier type for the
      TSM and the mTSM were compared. For control carriers, the mean log densities per
      carrier (for each carrier material) were not significantly different based on the
      TSM compared to the mTSM. Furthermore, the treated carrier data showed comparable
      LR values for the TSM and mTSM. The data provided in this report demonstrate
      equivalency between the TSM and mTSM and support the proposed procedural
      modification to consolidate fractions B and C.

PMID- 24282931
TI  - Validated stability-indicating capillary electrophoresis method for the
      separation and determination of a fixed-dose combination of carvedilol and
      hydrochlorothiazide in tablets.
AB  - A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique
      coupled to a diode array detector has been developed for the separation and
      simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in
      two combination formulations. The proposed method utilized a fused silica
      capillary (55 cm x75 microm id) and the background electrolyte solution phosphate
      buffer (12.5 mM, pH 7.4)-methanol (95+5, v/v). The separation was achieved at 30
      kV applied voltage and 24 degree C. Atorvastatin (80 microg/mL) was chosen as the
      internal standard. The described method was linear over the range of 1-200 and
      0.2-150 microg/mL for CRV and HCT, respectively. Intraday and interday RSD (n =
      6) was < or =1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 microg/mL,
      respectively. The validated CE method was successfully applied to the analysis of
      two commercial tablet dosage forms. Forced degradation studies were performed on
      bulk samples of the two drugs using thermal, photolytic, hydrolytic, and
      oxidative stress conditions, and the stressed samples were analyzed by the
      proposed method. Degradation products produced as a result of stress studies did
      not interfere with the determination of CRV and HCT; the assay could, therefore,
      be considered stability-indicating.

PMID- 24282932
TI  - Multivariate development and validation of a stability-indicating HPLC method for
      the determination of glimepiride in tablets.
AB  - This paper describes the multivariate development of a stability-indicating HPLC
      method for the quantification of glimepiride in pharmaceutical tablets. Full
      factorial design, Doehlert design, and response-surface methodology were used in
      conjunction with the desirability function approach. This procedure allowed the
      adequate separation of glimepiride from all degradant peaks in a short analysis
      time (about 9 min). This HPLC method uses potassium phosphate buffer (pH 6.5;
      27.5 mmol/L)-methanol (34 + 66, v/v) mobile phase at a flow rate of 1.0 mL/min
      and UV detection at 228 nm. A Waters Symmetry C18 column (250 x 4.6 mm, 5.0 pm)
      at controlled room temperature (25 degrees C) was used as the stationary phase.
      The method was validated according to International Conference on Harmonization
      guidelines and demonstrated linearity from 2 to 40 mg/L glimepiride, selectivity,
      precision, accuracy, and robustness. The LOD and LOQ were 0.315 and 1.050 mg/L,
      respectively. The multivariate strategy adopted in this work can be successfully
      applied in routine laboratories because of its fast optimization without the
      additional cost of columns or equipment.

PMID- 24282933
TI  - Utility of 4-chloro-7-nitrobenzofurazan (NBD-CI) for the Spectrophotometric and
      spectrofluorometric determination of several antihistamine and antihypertensive
      drugs.
AB  - New, sensitive, and selective spectrophotometric and spectrofluorometric methods
      have been developed for determination of clemastine hydrogen fumarate (Clem),
      loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form
      and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-CI),
      which is a highly sensitive chromogenic and fluorogenic reagent. The relation
      between absorbance at 470, 467, 471, and 469 nm and the concentration was linear
      over the ranges 5-35, 10-100, 10-90, and 10-120 microg/mL for Clem, Lor, Los, and
      Ram, respectively. The complexation products were also measured
      spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram
      and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor,
      respectively, and 460 nm for both Los and Ram. The fluorescence intensity was
      directly proportional to the drug concentration over the ranges 0.05-0.5, 5-20, 1
      6, and 2-15 microg/mL for Clem, Lor, Los, and Ram, respectively. The methods were
      successfully applied for the determination of the studied drugs in pharmaceutical
      dosage forms with excellent recovery.

PMID- 24282934
TI  - Enantioselective quantification of atenolol in mouse plasma by high performance
      liquid chromatography using a chiral Stationary phase: application to a
      pharmacokinetic study.
AB  - Enantiomeric resolution of atenolol was achieved on the HPLC vancomycin
      macrocyclic antibiotic chiral stationary phase Chirobiotic V. The polar ionic
      mobile phase consisted of methanol-glacial acetic acidtriethylamine (100 + 0.025
      + 0.75, v/v/v) at a flow rate of 0.8 mL/min. Fluorescence detection at 2751305 nm
      for excitation and emission, respectively, was used. Plasma samples were purified
      using SPE on Oasis HLB cartridges. The calibration curves in plasma were linear
      over the range of 5-400 ng/mL (r = 0.999) for each enantiomer with an LOD of 1.0
      ng/mL. The proposed method was validated in compliance with International
      Conference of Harmonization guidelines in terms of linearity, accuracy,
      precision, LOD, LOQ, and selectivity. The overall recoveries for S-(-)- and R-(+)
      atenolol enantiomers from plasma were 95.0-99.5%; RSD ranged from 2.5 to 3.3%.
      The developed method was applied for the trace analysis of atenolol enantiomers
      in plasma and for the pharmacokinetic investigation of atenolol enantiomers in
      mouse plasma.

PMID- 24282935
TI  - A novel validated ultra-performance liquid chromatography Method for separation
      of eszopiclone impurities and its degradants in drug products.
AB  - A selective, specific, and sensitive ultra-performance LC (UPLC) method was
      developed for determination of eszopiclone and its degradation products. The
      chromatographic separation was performed with a Waters ACQUITY UPLC system and
      BEH C18 column using gradient elution with mobile phases A and B. Mobile phase A
      was 0.01 M phosphate buffer with 0.2% (w/v) 1-octane sulfonic acid sodium salt as
      an ion pair reagent, adjusted pH 2.2 with orthophosphoric acid-acetonitrile (85 +
      15, v/v). Mobile phase B was pH 2.2 buffer-acetonitrile (20 + 80, v/v). UV
      detection was performed at 303 nm. Eszopiclone and its impurities were
      chromatographed with a total run time of 13 min. A calibration study showed that
      the response for each of the impurities A, B, C, and D was linear between
      concentrations of 0.02 and 7.2 microg/mL (r2 > or = 0.999). The method was
      validated over this range for precision, intermediate precision, accuracy,
      linearity, and specificity. For the precision study, RSD of each impurity was <5%
      (n = 6). The method was found to be precise, accurate, linear, and specific. The
      proposed method was successfully used for determination of eszopiclone impurities
      in pharmaceutical preparations.

PMID- 24282936
TI  - Determination of methoxamine in human plasma and urine by a validated HPLC
      fluorescence detection method.
AB  - A sensitive HPLC method for the determination of methoxamine in human plasma and
      urine is described. The method is based on derivatization of methoxamine with 4
      chloro-7-nitrobenzofurazan in borate buffer of pH 9.5 to yield a yellow,
      fluorescent product. Isocratic HPLC separation was achieved on an Inertsil C18
      column (250 x4.6 mm id, 5 microm particle size) using the mobile phase methanol
      water (60+40, v/v) at a flow rate of 1.2 mL/min. Fluorescence detection was used
      at excitation and emission wavelengths of 458 and 521 nm, respectively. The assay
      was linear over the concentration ranges of 10-250 and 20-300 ng/mL for plasma
      and urine, respectively. The LOD values were 3.3 and 6.8 ng/mL and the LOQ values
      were 10 and 20 ng/mL for plasma and urine, respectively. The extraction
      recoveries were more than 97.10%. After strict validation, the method indicated
      good performance in terms of linearity, sensitivity, precision, accuracy
      (recovery), robustness, and system suitability, and it was successfully applied
      to the determination of methoxamine in human plasma and urine.

PMID- 24282937
TI  - Evaluation of the culture method NIHSJ-02 alternative to ISO 10272-1:2006 for the
      detection of campylobacter jejuni and campylobacter coli in chicken:
      collaborative study.
AB  - For the surveillance of the prevalence of Campylobacter jejuni and Campylobacter
      coli in raw chicken products in Japan, a qualitative method, National Institute
      of Health Sciences Japan (NIHSJ)-02, was developed as an alternative to
      International Organization for Standardization (ISO) 10272-1:2006. In the NIHSJ
      02 culture method, the enrichment step is carried out in a reduced volume of
      Preston broth at 42 +/- 1 degrees C to reduce cost and space, and to prevent the
      overgrowth of background bacteria. To evaluate the performance of NIHSJ-02, a
      collaborative study was conducted, and the results obtained by NIHSJ-02 were
      compared with those obtained using the reference method, ISO 10272-1:2006.
      Fifteen laboratories participated; each examined 48 minced chicken samples
      consisting of test samples uninoculated, inoculated with C. jejuni at a low or
      high level, and inoculated with C. coli at a low level. The average probabilities
      of detection by NIHSJ-02 across laboratories were 0.033, 0.222, 0.678, and 0.267
      in samples uninoculated, inoculated with C. jejuni at a low and high level, and
      with C. coli at a low level, respectively. Those by ISO 10272-1:2006 were 0.051,
      0.128, 0.551, and 0.090. Significantly higher probabilities of detection were
      determined by NIHSJ-02 compared to ISO 10272-1:2006, except for uninoculated
      samples. On the other hand, significantly lower frequency of occurrence of
      background bacteria was observed by NIHSJ-02 (43.1%) compared with ISO 10272
      1:2006 (92.6%). NIHSJ-02 showed better performance than ISO 10272-1:2006 with
      regard to the selective detection of C. jejuni and C. coli in chicken.

PMID- 24282938
TI  - The need for harmonization in detection of human noroviruses in food.
AB  - Noroviruses (NoV) have been recognized worldwide as a leading cause of foodborne
      gastroenteritis over the last decade. A broad range of foods- shellfish, fresh
      produce, and ready-to-eat/catered foods-has been implicated in NoV foodborne
      outbreaks. The recognition of NoV as an important food pathogen has been aided by
      the development of sensitive molecular methods for detection of the NoV genome.
      However, despite advances, NoV detection is still hampered by several
      limitations. First, NoV detection can often only be implemented by expert
      laboratories due to the complexity of the virus extraction step, which in most
      protocols is cumbersome and labor-intensive. Moreover, a very wide selection of
      automated methods for virus extraction from foods is available, so selection of
      an adequate method is not straightforward. On the other hand, automated systems
      have been made available or the RNA purification and real-time RT-PCR (RT-qPCR)
      is considered the gold standard for detection of NoV. Second, correct
      interpretation of real-time PCR results is often difficult. From a technical
      point of view, the interpretation of the often nonsigmoidal amplification curves
      remains difficult, even for experts. From a food safety perspective,
      interpretation of very high Cq (or Ct) values-and thus, of low viral genomic copy
      numbers-is not straightforward, as RT-(q)PCR merely detects the presence of viral
      genomic material that is not necessarily linked to the presence of infectious
      viral particles. Despite efforts, both limitations have not completely resolved
      thus far. Harmonization may be a first step to comprehend and deal with these
      limitations. The current review provides an overview of a number of validated
      methods that have been published by food safety and other authorities.

PMID- 24282939
TI  - QuickTox Kit for QuickScan DON (Vomitoxin).
AB  - The QuickTox Kit for QuickScan DON (Vomitoxin) uses lateral flow technology and a
      reader-based system for the quantification of deoxynivalenol (DON, vomitoxin)
      residues in cereal grain commodities. The present work was performed to obtain
      AOAC Research Institute Performance Tested MethodsM certification for testing
      wheat, maize, wheat bran, wheat flour, and barley samples with DON contamination
      levels as high as 5 ppm. Assay performance was examined using naturally
      contaminated and spiked samples in internal and independent laboratory
      evaluations and was compared to previously established acceptance criteria.
      Performance was evaluated with direct regard to linearity, matrix, selectivity,
      robustness, and stability. All data points in all studies were within the ranges
      defined in the acceptance criteria. The assay exhibited a linear dose response
      over the range tested, 0-5.0 ppm, with R2 values exceeding 0.97. RSD of
      repeatability, or RSDr, values for results ranged from 3.12 to 16.01% across all
      tested commodities and levels. Assay results were not affected by the presence of
      other common mycotoxins: aflatoxin B1, fumonisin B1, ochratoxin A, or
      zearalenone. Selectivity for modified DON was examined, specifically 15-acetyl
      DON, 3-acetyl DON, DON-3-glucoside, and another tricothecene, nivalenol; all were
      detected. The assay produced acceptable results in robustness studies when assay
      timing, temperature, and volume were covaried. The QuickTox Kit for QuickScan DON
      (Vomitoxin) assay is a convenient and reliable method for determination of DON in
      grain commodities.

PMID- 24282940
TI  - Determination of aflatoxins B1, B2, G1, and G2 in olive oil, peanut oil, and
      sesame oil using immunoaffinity column cleanup, postcolumn derivatization, and
      liquid chromatography with fluorescence detection: first action 2013.05.
AB  - A collaborative study of a method for determination of aflatoxins (AFs) B1, B2,
      G1, and G2 in olive oil, peanut oil, and sesame oil using immunoaffinity column
      cleanup, postcolumn derivatization, and LC with fluorescence detection,
      previously published in J. AOAC Int. 95, 1689-1700 (2012), was approved as First
      Action 2013.05 on March 29, 2013 by the Method-Centric Committee for Aflatoxins
      in Edible Oils. The method uses methanol for extraction followed by filtration.
      The extract is applied to an immunoaffinity column with antibodies specific for
      AFs, which are then eluted from the column with a methanol solution.
      Determination and quantification occur using RP-LC with fluorescence detection
      after postcolumn derivatization. The average recovery of AFs in olive, peanut,
      and sesame oils in spiked samples (levels between 2.0 and 20.0 microg/kg) ranged
      from 84 to 92%. The recoveries for AFs B1, B2, G1, and G2 were 86-93, 89-95, 85
      97, and 76-85%, respectively. Within-laboratory RSD (RSDr) values for AFs ranged
      from 3.4 to 10.2%. RSDr values forAF B1, B2, G1, and G2 were 3.5-10.9, 3.2-9.5,
      6.5-14.9, and 4.8-14.2%, respectively. Between-laboratory RSD (RSDR) values for
      AFs were 6.1-14.5%. RSD, values for AFs B1, B2, G1, and G2 were 7.5-15.4, 7.1
      14.6, 10.8-18.1, and 7.6-23.7%, respectively. Horwitz ratio values were < or =2
      for the analytes in the three matrixes.

PMID- 24282941
TI  - QuickTox Kit for QuickScan Ochratoxin-A.
AB  - Quantitative, reader-based lateral flow technology is utilized for determination
      of ochratoxin contamination levels in wheat by the QuickTox Kit for QuickScan
      Ochratoxin-A. Naturally contaminated wheat samples were used to challenge the
      assay in the range of 0-100 ppb in linearity, selectivity, robustness, and
      stability, and in internal and external matrix studies. Performance was judged
      against criteria established by the AOAC Research Institute Performance Tested
      Method program prior to beginning the validation studies. All data produced
      during this work conformed to the acceptance criteria. Linear dose responses with
      R2 exceeding 0.97 and RSDr values between 6.22 and 17.10% for positive samples
      were observed in linearity and internal and external matrix studies. Ochratoxin A
      (OTA) and ochratoxin B (OTB) were detected by the assay. Assay sensitivity
      towards OTB was approximately 50% relative to OTA detection. Other common
      mycotoxins did not affect assay results. Variations in assay timing, temperature,
      and sample volume encompassed in the robustness study did not yield results
      outside the acceptable range. Determination of ochratoxin in wheat is facilitated
      using the QuickTox Kit for QuickScan Ochratoxin-A kit.

PMID- 24282942
TI  - Determination of bovine immunoglobulin G in bovine colostrum powders, bovine milk
      powders, and dietary supplements containing bovine colostrum products by an
      automated direct immunoassay with optical biosensor: collaborative study.
AB  - Nine laboratories participated in an AOAC collaborative study to determine bovine
      immunoglobulin G (IgG) levels in selected dairy powders and dietary supplements
      by surface plasmon resonance (SPR) methodology. Each sample matrix was dissolved
      in buffer and suitably diluted to fit within the standard curve. The sample
      extract was injected over a surface functionalized with affinity-purified,
      polyclonal goat anti-bovine IgG (H+L) antibody; IgG was then detected. SPR
      detection was used for the direct immunoassay and quantification was made against
      a calibration curve prepared from bovine serum IgG. Between each standard and
      sample, the surface was regenerated using 10 mM glycine at pH 1.5. The samples
      analyzed included the likely matrixes for which the assay would find commercial
      use, namely, high- and low-protein-content colostrum powders, tablets containing
      colostrum powder, infant formula containing colostrum powder, and some IgG
      containing dairy powders, i.e., milk protein isolate, whey protein concentrate,
      and skim milk powder. Each laboratory provided data for the study and assayed
      blind duplicates of seven materials. Due to gross outliers in the majority of
      results from one laboratory, the data from eight laboratories were used for the
      statistical analysis. The repeatability RSD (RSDr) values ranged from 3.2 to
      7.3%, and the reproducibility RSDR values from 13.0 to 22.6%.

PMID- 24282943
TI  - Validation procedures for quantitative gluten ELISA methods: AOAC allergen
      community guidance and best practices.
AB  - The food allergen analytical community is endeavoring to create harmonized
      guidelines for the validation of food allergen ELISA methodologies to help
      protect food-sensitive individuals and promote consumer confidence. This document
      provides additional guidance to existing method validation publications for
      quantitative food allergen ELISA methods. The gluten-specific criterion provided
      in this document is divided into sections for information required by the method
      developer about the assay and information for the implementation of the
      multilaboratory validation study. Many of these recommendations and guidance are
      built upon the widely accepted Codex Alimentarius definitions and recommendations
      for gluten-free foods. The information in this document can be used as the basis
      of a harmonized validation protocol for any ELISA method for gluten, whether
      proprietary or nonproprietary, that will be submitted to AOAC andlor regulatory
      authorities or other bodies for status recognition. Future work is planned for
      the implementation of this guidance document for the validation of gluten methods
      and the creation of gluten reference materials.

PMID- 24282944
TI  - ELISA kit for peanut protein determination: collaborative study.
AB  - A collaborative study in 10 laboratories was performed to validate an ELISA
      method developed for the quantitative determination of peanut protein in foods.
      The ELISA kit used for this study is based on rabbit polyclonal antibody. This
      kit does not produce any false-positive results or cross-reactivity with a broad
      range of peanut-free food matrixes. All participants obtained the peanut ELISA
      kit with standard operational procedures, a list of samples, the samples, and a
      protocol for recording test results. The study included 15 food samples. Three
      food matrix samples of zero peanut content showed peanut protein content lower
      than the first standard (0.10 mg/kg). Three samples with peanut declared as an
      ingredient revealed peanut protein content outside the calibration curve
      (absorbance was above the highest standard) in all laboratories, and three
      samples had the peanut content reported either above the highest standard or
      within the calibration curve, depending on the laboratory. Six samples with
      peanut declared as an ingredient gave the peanut protein content within the
      calibration curve. Only these six samples, together with a positive control
      sample (CS2), were used for statistical evaluation. The statistical tests
      (Cochran, Grubbs, and Mandel) and analysis of variance were used for the
      evaluation of the collaborative study results. Repeatability and reproducibility
      limits, as well as an LOQ (LOQcollaborative 0.22 mg peanut proteins/kg) and an
      LOD (LODcollaborative 0.07 mg peanut proteinslkg) for the kit were calculated.

PMID- 24282945
TI  - A geographical discrimination of Shanxi extra aged vinegars using polyalcohols as
      the discriminators.
AB  - A discrimination method based on polyalcohol determination was developed for
      authenticity of protected geographical indication (PGI) vinegars-Shanxi extra
      aged vinegar (SVs) in China. Six polyalcohols in vinegars including erythritol,
      arabitol, xylitol, inositol, mannitol, and sorbitol were selected as the PGI
      discriminators. GC/MS was used to analyze the polyalcohols in the SVs, Zhenjiang
      vinegars (ZVs), Kazuo aged vinegars (KVs), and other non-geographical indication
      protected vinegars (NVs). SVs can be distinguished from KVs by the chemical
      markers mannitol and sorbitol, although the production processes for both types
      of vinegars are similar. Principal component analysis (PCA) was used to
      distinguish SVs from ZVs and NVs. The differences among the three kinds of
      vinegars shown by PCA results may be due to the higher erythritol content in SVs,
      and the inositol and mannitol in ZVs. This study also found that the amount of
      polyalcohols in Chinese vinegars increases with the acidity value only,
      regardless of the aging time. The overall results indicated that the polyalcohols
      can be practicable discriminators for SV discrimination.

PMID- 24282946
TI  - Interlaboratory validation study of an event-specific real-time polymerase chain
      reaction detection method for genetically modified 55-1 papaya.
AB  - Genetically modified (GM) papaya line 55-1 (55-1) is resistant to papaya ringspot
      virus infection, and is commercially available in several countries. A specific
      detection method for 55-1 is required for mandatory labeling regulations. An
      event-specific real-time PCR method was developed by our laboratory. To validate
      the method, interlaboratory validation of event-specific qualitative real-time
      PCR analysis for 55-1 was performed in collaboration with 12 laboratories. DNA
      extraction and real-time PCR reaction methods were evaluated using 12 blind
      samples: six non-GM papayas and six GM papayas in each laboratory. Genomic DNA
      was highly purified from all papayas using an ion-exchange column, and the
      resulting DNA sample was analyzed using real-time PCR. Papaya endogenous
      reference gene chymopapain (CHY) and the event-specific 55-1 targeted sequence
      were detected in GM papayas whereas CHYalone was detected in non-GM papayas in
      all laboratories. The cycle threshold values of CHYand the 55-1 targeted sequence
      showed high repeatability (RSD, 0.6-0.8%) and reproducibility (RSDR 2.2-3.6%).
      This study demonstrates that the 55-1 real-time PCR detection method is a useful
      and reliable method to monitor 55-1 papaya in foods.

PMID- 24282947
TI  - Rapid method for the simultaneous determination of flavonol aglycones in food
      using u-HPLC coupled with heating block acidic hydrolysis.
AB  - A rapid method for the simultaneous determination of flavonol aglycones in food
      using ultra-high-performance LC (u-HPLC) coupled with a heating-block acidic
      hydrolysis method was validated in terms of precision, accuracy, and linearity.
      The u-HPLC separation was performed on an RP C18 column (particle size 2 micro m
      id, 2 mm, length 100 mm) with a photodiode array detector. The LOD and LOQ of the
      u-HPLC analyses were 0.15 and 0.47 mg/kg for myricetin, 0.09 and 0.28 mg/kg for
      quercetin, 0.16 and 0.49 mg/kg for kaempferol, and 0.08 and 0.25 mg/kg for
      isorhamnetin. The intraday and interday precisions of the individual flavonol
      aglycones were less than 9.31%. All calibration curves exhibited good linearity
      (r2 = 0.99) within the tested ranges. Total run time of u-HPLC was 13 min. The
      rapid u-HPLC method presented herein significantly improved the speed,
      sensitivity, and resolution of the analyses of myricetin, quercetin, kaempferol,
      and isorhamnetin in food.

PMID- 24282948
TI  - Vitamin C in infant formula and adult/pediatric nutritional Formula by ultra
      performance liquid chromatography with Ultraviolet detection: first action
      2012.22.
AB  - During the AOAC Annual Meeting held in Las Vegas, NV from September 30 to October
      3, 2012, the Stakeholder Panel on Infant Formula and Adult Nutritionals convened
      to review single-laboratory validation data submitted for the method, Vitamin C
      in Adult/Pediatric Formula by Ultra-Performance Liquid Chromatography with
      Ultraviolet Detection. This method is a modified version of the method "HPLC-UV
      Determination of Total Vitamin C in a Wide Range of Fortified Food Products"
      previously published in Food Chem., 94, 626-631 (2006). The SLV data from the
      modified method were reviewed and compared to the standard method performance
      requirements (SMPR 2012.012), and it was concluded that the method meets the
      requirements. The method was approved as AOAC Official First Action. The method
      is based on the acidic extraction of ascorbic acid in the presence of Tris[2
      carboxyethyl] phosphine (TCEP) as a reducing agent. Separation was achieved on a
      C18 column with a sodium acetate eluent (pH 5.4) combined with TCEP and
      decylamine as an ion-pairing agent. Accuracy rates were between 90 and 100%.
      Repeatability RSD (RSD,) ranged from 1.4 to 2.5%, and intermediate
      reproducibility RSD (RSDiR) ranged from 1.3 to 7.5%.

PMID- 24282949
TI  - Determination of free and total myo-inositol in infant formula and
      adult/pediatric nutritional formula by high- performance anion exchange
      chromatography with pulsed amperometric detection, including a novel total
      extraction using microwave-assisted acid hydrolysis and enzymatic treatment:
      first action 2012.12.
AB  - After an assessment of data generated from a single-laboratory validation study
      published in J. AOAC Int. 95, 1469-1478 (2012), a method for determining total
      myo-inositol in infant formula and adult/ pediatric nutritional formula by high
      performance anion exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD), including extraction by using microwave-assisted acid hydrolysis and
      enzymatic treatment was presented for consideration by AOAC during the AOAC
      Annual Meeting held in Las Vegas, NV, from September 30 to October 3, 2012. The
      Expert Review Panel on Infant Formula and Adult Nutritionals concluded that the
      method met the criteria set by the standard method performance requirements
      (SMPRs) for the determination of free myo-inositol and approved the method as
      AOAC Official First Action. The method also determines total myo-inositol, but
      includes bound sources that the SMPRs exclude. The method involves using HPAEC
      PAD for free myo-inositol and a total myo-inositol determination by two different
      techniques. The first technique uses the conventional acid hydrolysis with 6 h
      incubation in an autoclave. The second uses a microwave-assisted acid hydrolysis
      with enzymatic treatment that decreases the extraction time.

PMID- 24282950
TI  - Simultaneous determination of 13-cis and all-trans vitamin A palmitate (retinyl
      palmitate), vitamin A acetate (retinyl acetate), and total vitamin E (alpha
      tocopherol and DL-alpha-tocopherol acetate) in infant formula and adult
      nutritionals by normal phase HPLC: first action 2012.10.
AB  - This HPLC method, with both variable UV and fluorescence detection, allows for
      the simultaneous determination of vitamin A palmitate, vitamin A acetate, and
      total vitamin E in infant, pediatric, and adult nutritional formulas. The
      concentration of each vitamin form is calculated by comparison with standards of
      known concentration. Following hydrolysis, the vitamins are extracted into iso
      octane and analyzed by normal phase (NP) HPLC. The method was evaluated for
      linearity, precision, and accuracy using a selection of the Stakeholder Panel on
      Infant Formula and Adult Nutritionals (SPIFAN) matrixes, including milk-based,
      soy-based, and hydrolyzed protein, as well as high- and low-fat products. A
      single-laboratory validation has been completed for all analytes using a
      selection of SPIFAN matrixes. Performance parameters included a working range of
      2-450 microg/100 g ready-to-feed for vitamin A and 0.03-8.0 mgl100 g
      reconstituted final product for vitamin E. LOD was <1.0 microg and <0.1 mgl100 g
      reconstituted final product for vitamins A and E, respectively; RSD was 1.08
      8.70% over a range of concentration; and average recoveries of 97.4-101.3%.
      Repeatability of <4% for vitamin A and <8% for vitamin E was calculated from five
      laboratories using this method. Results indicate that this method is suitable for
      the analysis of vitamins A and E in all forms of infant, adult, and pediatric
      formulas (powders, ready-to-feed liquids, and liquid concentrates). The Expert
      Review Panel (ERP) of Infant Formula reviewed this method separately for vitamins
      A and E, including all available method validation data at the AOAC INTERNATIONAL
      Annual Meeting on September 29, 2012. Following evaluation of the data for both
      methods, the ERP agreed that both methods met the standard method performance
      requirements articulated by SPIFAN. The ERP granted First Action status to both
      methods, and recommended that a single method be published for the simultaneous
      determination of vitamin A palmitate, vitamin A acetate, and total vitamin E (DL
      a-tocopherol and DL-alpha-tocopherol acetate) in infant formula and adult
      nutritionals by NP HPLC.

PMID- 24282951
TI  - Free and total carnitine in infant and adult/pediatric nutritional formulas by
      liquid chromatography/tandem mass spectrometry: first action 2012.17.
AB  - Data from a previously published study in J. AOAC Int. 91,130-142 (2008) was
      presented to the Stakeholder Panel on Infant Formula and Adult Nutritionals
      (SPIFAN) during the AOAC Annual Meeting held in Las Vegas, NV, from September 30
      to October 3, 2012. The panel reviewed the data submitted and concluded that the
      method satisfied the standard method performance requirements established by
      SPIFAN. Based on this information, the panel approved the method as AOAC First
      Action. The determination of free carnitine involves dilution and filtration of
      the sample, followed by determination of L-carnitine by LC/MS/MS. The
      determination of total carnitine includes a saponification procedure prior to
      dilution and filtration.

PMID- 24282952
TI  - Determination of the relative level of detection of a Qualitative microbiological
      measurement method with respect to a reference measurement method.
AB  - Performance of qualitative microbiological measurement methods where the results
      are either "O" (microorganism not detected) or "1" (microorganism detected) is
      described by their probability of detection (POD) function, i.e., the POD as a
      function of the level of contamination of the sample, expressed as CFU/g or
      CFU/mL, or by the level of detection (LODp), i.e., the contamination of the
      sample that is detected (measurement result "1") with a specified probability p.
      When it is impossible to obtain samples of known contamination, estimation of the
      POD and LOD is impossible. However, it may not be the LOD of the method that is
      of interest, but its LOD with respect to the LOD of a reference method. Hence, an
      intralaboratory experiment is performed with a reference method, R, and an
      alternative method, A, at different levels of unknown contamination. A
      complementary loglog model is used to statistically estimate the relative LOD
      (RLOD) of A with respect to R that is equal for all chosen values p of the POD.
      An intralaboratory experiment for the detection of Listeria monocytogenes in fish
      and eggs illustrates the method. In a simulation study, the bias of the estimate
      of the RLOD was investigated. This bias is due to the small number of repeated
      measurements in intralaboratory studies; the relative bias increases with
      increasing true values of the RLOD from 0 for true RLOD = 1 to about 20% for true
      RLOD = 3. If the number of CFUs in the test portions does not follow a Poisson
      distribution, but instead follows a negative binomial distribution, e.g., because
      of overdispersion, the bias of the estimate of the RLOD decreases. An EXCEL
      program RLOD_ver1. xlsm for this method of statistical analysis can be downloaded
      from http://www.wiwiss.fu-berlin.de/
      instituteliso/mitarbeiterlwilrichlindex.html.

PMID- 24282953
TI  - An automated online turboflow cleanup LC/MS/MS method for the determination of 11
      plasticizers in beverages and milk.
AB  - An automated sample preparation technique involving cleanup and analytical
      separation in a single operation using an online coupled TurboFlow (RP-LC system)
      is reported. This method eliminates time-consuming sample preparation steps that
      can be potential sources for cross-contamination in the analysis of plasticizers.
      Using TurboFlow chromatography, liquid samples were injected directly into the
      automated system without previous extraction or cleanup. Special cleanup columns
      enabled specific binding of target compounds; higher MW compounds, i.e., fats and
      proteins, and other matrix interferences with different chemical properties were
      removed to waste, prior to LC/MS/MS. Systematic stepwise method development using
      this new technology in the food safety area is described. Selection of optimum
      columns and mobile phases for loading onto the cleanup column followed by
      transfer onto the analytical column and MS detection are critical method
      parameters. The method was optimized for the assay of 10 phthalates (dimethyl,
      diethyl, dipropyl, butyl benzyl, diisobutyl, dicyclohexyl, dihexyl, diethylhexyl,
      diisononyl, and diisododecyl) and one adipate (diethylhexyl) in beverages and
      milk.

PMID- 24282954
TI  - Determination of arsenic, cadmium, mercury, and lead in foods by pressure
      digestion and inductively coupled plasma/ mass spectrometry: first action
      2013.06.
AB  - The method for the determination of As, Cd, Hg, and Pb in foods by pressure
      digestion and inductively coupled plasma (ICP)/MS, previously published in J.
      AOAC Int. 90, 844-856 (2007), was approved as First Action 2013.06 on April 9,
      2013 by the Method- Centric Committee for Elemental Contaminants in Food.
      Digestion occurs using nitric acid in a closed vessel with elevated temperature
      and pressure by conventional or microwave-assisted heating. Determination occurs
      using ICP/MS. The elemental concentration ranges for As were 0.06-21.4, for Cd
      0.03-28.3, for Hg 0.04-0.6, and for Pb 0.01-2.4 in mg/kg dry matter. The
      repeatability RSD (RSDr) ranged from 3.8 to 24% for As, 2.6 to 6.9% for Cd, 4.8
      to 8.3% for Hg, and 2.9 to 27% for Pb. Reproducibility RSD (RSDR) ranged from 9.0
      to 28% for As, 2.8 to 18% for Cd, 9.9 to 24% for Hg, and 8 to 50% for Pb.

PMID- 24282955
TI  - Determination of free sulfites (SO3-2) in dried fruits processed with sulfur
      dioxide by ion chromatography through anion exchange column and conductivity
      detection.
AB  - A simple and effective anion ion chromatography (IC) method with anion exchange
      column and conductivity detector has been developed to determine free sulfites
      (SO3-2) in dried fruits processed with sulfur dioxide. No oxidation agent, such
      as hydrogen peroxide, is used to convert sulfites to sulfates for IC analysis. In
      addition, no stabilizing agent, such as formaldehyde, fructose or EDTA, is
      required during the sample extraction. This method uses aqueous 0.2 N NaOH as the
      solvent for standard preparation and sample extraction. The sulfites, either
      prepared from standard sodium sulfite powder or extracted from food samples, are
      presumed to be unbound SO3-2 in aqueous 0.2 N NaOH (pH > 13), because the bound
      sulfites in the sample matrix are released at pH > 10. In this study, sulfites in
      the standard solutions were stable at room temperature (i.e., 15-25 degrees C)
      for up to 12 days. The lowest standard of the linear calibration curve is set at
      1.59 microg/mL SO3-2 (equivalent to 6.36 microg/g sample with no dilution) for
      analysis of processed dried fruits that would contain high levels (>1000
      microg/g) of sulfites. As a consequence, this method typically requires
      significant dilution of the sample extract. Samples are prepared with a simple
      procedure of sample compositing, extraction with aqueous 0.2 N NaOH,
      centrifugation, dilution as needed, and filtration prior to IC. The sulfites in
      these sample extracts are stable at room temperature for up to 20 h. Using anion
      IC, the sulfites are eluted under isocratic conditions with 10 mM aqueous sodium
      carbonate solution as the mobile phase passing through an anion exchange column.
      The sulfites are easily separated, with an analysis run time of 18 min,
      regardless of the dried fruit matrix. Recoveries from samples spiked with sodium
      sulfites were demonstrated to be between 81 and 105% for five different fruit
      matrixes (apricot, golden grape, white peach, fig, and mango). Overall, this
      method is simple to perform and effective for the determination of high levels of
      sulfites in dried fruits.

PMID- 24282956
TI  - Faster extraction of heavy metals from soils using vacuum and ultrasonic energy.
AB  - A fast vacuum- and ultrasound-assisted acid extraction of Co, Cu, Fe, Mn, Pb, and
      Zn from soils using a homemade system has been investigated. Preliminarily, a
      full factorial design with two levels and three variables (extracting agent,
      extraction temperature, and sonication time) was applied to optimize the
      extraction conditions (without vacuum) for some heavy metals (Cu, Mn, Pb, and
      Zn). The best results were obtained with a 3:1 HCI extraction solution,
      temperature of 80 degrees C, and time of 2 h. As this sonication time was too
      long, a vacuum pump was used to produce air bubbles in order to increase the
      contact between the sample and the extracting agent and to prevent the sample
      sedimentation. This improvement drastically reduced the sonication time to 2 min.
      Under these conditions, Co, Cu, Mn, and Zn were totally extracted (recoveries of
      86-99%), while recoveries of 73-76 and 74% were obtained for Fe and Pb,
      respectively. The LOD values using flame atomic absorption spectrometry for
      determination of Co, Cu, Fe, Mn, Pb, and Zn were 3.2, 7.5, 37.5, 7.5, 22.5, and
      3.8 micro glg, respectively. The RSDs were lower than 11% (n = 3).

PMID- 24282957
TI  - Ultra-high performance liquid chromatography/ electrospray ionization-tandem mass
      spectrometry determination of 151 pesticides in soybeans and pulses.
AB  - This paper presents the application of ultra-high performance LC (UHPLC) and MS
      for the determination of 151 pesticides in soybeans and pulses. A core-shell
      particle (2.6 micro m particle size) column and a fully porous sub-2 microm (1.7
      microm particle size) column showed comparable performance in chromatographic
      resolution and separation, increasing selectivity, and reducing analysis time.
      UHPLC was coupled with either a triple quadrupole mass analyzer (MS/MS) or a
      quadrupole Orbitrap (namely Orbital trap) mass spectrometer (Q-Orbitrap MS),
      which possesses fast data acquisition capability. Both configurations yielded
      analytical run times of < or =14 min. Soybean and pulse samples were analyzed and
      quantitated for pesticide residues using the QuEChERS (Quick, Easy, Cheap,
      Effective, Rugged, and Safe) procedure, UHPLC/electrospray ionization (ESI)
      MS/MS, and matrix-matched standard calibration curves (in an analytical range of
      5-500 microg/kg) with isotopically-labeled standards or a chemical analog as
      internal standards. The method performance parameters that included overall
      recovery, intermediate precision, and measurement uncertainty were evaluated
      according to a nested design experiment. Approximately 89% of the pesticides
      studied had recoveries between 81 and 110%; 95%, had intermediate precision < or
      =20%; and 93% showed measurement uncertainty < or =40%. From a pilot study of 100
      samples, eight tested positive by UHPLCIESI-MS/MS for carbendazim, methomyl, or
      imidacloprid. These pesticides were further confirmed using UHPLC/ESI-Q-Orbitrap
      MS based on accurate mass measurement with mass error < or =5 ppm.

PMID- 24282958
TI  - Determination of chlorinated phenoxy acid herbicides in tobacco by modified
      quechERS extraction and high-performance liquid chromatography/tandem mass
      spectrometry.
AB  - A new method for determination of phenoxy acid herbicide residues in tobacco
      based on the use of liquid extraction/partition and dispersive SPE followed by
      HPLC/electrospray ionization-MS/MS is reported. Formic acid (2%, v/v) in
      acetonitrile as the extraction solvent and inclusion of citrate buffer helped
      partitioning of all analytes into the acetonitrile phase. Quantitative analysis
      was done in the multiple-reaction monitoring mode using two combinations of
      selected precursor ion and product ion transition for each compound. The
      recoveries obtained for each pesticide ranged between 85 and 110% at two spike
      concentration levels. Good linear relationships were observed, with the
      correlation coefficient (r2) >0.998 for all analytes. The method is simple,
      efficient, and sensitive, and each of its performance characteristics meets the
      requirements for determination of phenoxy acid herbicide residues in tobacco.

PMID- 24282959
TI  - Guidelines for the statistical analysis of a collaborative study of a laboratory
      method for testing disinfectant product performance.
AB  - This paper presents statistical techniques suitable for analyzing a collaborative
      study (multilaboratory study or ring trial) of a laboratory disinfectant product
      performance test (DPPT) method. Emphasis is on the assessment of the
      repeatability, reproducibility, resemblance, and responsiveness of the DPPT
      method. The suggested statistical techniques are easily modified for application
      to a single laboratory study. The presentation includes descriptions of the plots
      and tables that should be constructed during initial examination of the data,
      including a discussion of outliers and QA checks. The statistical recommendations
      deal with evaluations of prevailing types of DPPTs, including both quantitative
      and semiquantitative tests. The presentation emphasizes tests in which the
      disinfectant treatment is applied to surface-associated microbes and the outcome
      is a viable cell count; however, the statistical guidelines are appropriate for
      suspension tests and other test systems. The recommendations also are suitable
      for disinfectant tests using any microbe (vegetative bacteria, virus, spores,
      etc.) or any disinfectant treatment. The descriptions of the statistical
      techniques include either examples of calculations based on published data or
      citations to published calculations. Computer code is provided in an appendix.

PMID- 24282960
TI  - Determination of residues of three triphenylmethane dyes and their metabolites
      (malachite green, leuco malachite green, crystal violet, leuco crystal violet,
      and brilliant green) in aquaculture products by LC/MS/MS: first action 2012.25.
AB  - During the AOAC Annual Meeting held from September 30 to October 3, 2012 in Las
      Vegas, NV, the Expert Review Panel (ERP) on Veterinary Drug Residues reviewed
      data for the method for determination of residues of three triphenylmethane dyes
      and their metabolites (malachite green, leuco malachite green, crystal violet,
      leuco crystal violet, and brilliant green) in aquaculture products by LC/MS/MS,
      previously published in the Journal of Chromatography A 1218, 1632-1645 (2006).
      The method data were reviewed and compared to the standard method performance
      requirements (SMPRs) found in SMPR 2009.001, published in AOAC's Official Methods
      of Analysis, 19th Ed. (2012). The ERP determined that the data were acceptable,
      and the method was approved AOAC Official First Action. The method uses
      acetonitrile to isolate the analyte from the matrix. Then determination is
      conducted by LCIMS/MS with positive electrospray ionization. Accuracy ranged from
      100.1 to 109.8% for samples fortified at levels of 0.5, 0.75, 1.0, and 2.0
      microg/kg. Precision ranged from 2.0 to 10.3% RSD for the intraday samples and
      1.9 to 10.6% for the interday samples analyzed over 3 days. The described method
      is designed to accurately operate in the analytical range from 0.5 to 2
      microg/kg, where the minimum required performance limit for laboratories has been
      fixed in the European Union at 2.0 microg/kg for these banned substances and
      their metabolites. Upper levels of concentrations (1-100 microg/kg) can be
      analyzed depending on the different optional calibrations used.

PMID- 24282961
TI  - Determination of chloramphenicol in honey, milk, and egg by liquid
      chromatography/mass spectrometry: single-laboratory validation.
AB  - This study describes determination of chloramphenicol (CAP) in honey, milk, and
      egg by LC-electrospray ionization (ESI)-MS. CAP was extracted with ethyl acetate
      from honey, and with acetonitrile from milk and egg. d5-CAP was used as the
      internal standard. Separation was achieved on a ZORBAX Eclipse C18 2.1 id, 150
      mm, 2.1 pm column. The mass spectrometer was equipped with an ESI interface in
      negative mode. Mass determination of CAP and d5-CAP was carried out in selected
      ion monitoring mode by scanning m/z 321 for CAP and m/z 326 for d5-CAP as
      quantification ions, and m/z 323 as the confirmation ion. The validation of the
      analytical method was performed by carrying out linearity, LOD, LOQ, accuracy,
      precision, and recovery. Calibration curve was linear between 0.1 and 20.0 ng/g
      with correlation coefficient >0.998. Accuracy of the method for the honey sample
      was 95%, and for the milk powder sample 106%. Precision of the method, expressed
      as CV%, varied between 1.60 and 4.37 for intraday and 2.00 to 5.67 for interday.
      Quantification limits of method were 0.05, 0.08, and 0.09 ng/g for egg, milk, and
      honey, respectively. Recovery of the method ranged between 86 and 103% for all
      three matrixes and two different concentrations. Finally, the method was checked
      by participating proficiency tests from the Food Analysis Performance and
      Assessment Scheme 0281 and 0298 honey samples. Z scores were -1.0 and 0.4,
      respectively.

PMID- 24282962
TI  - Response to Ritner, M., K. K. Westerlund, C. D. Cooper, and M. Claggett. 2013.
      Accounting for acceleration and deceleration emissions in intersection dispersion
      modeling using MOVES and CAL3QHC. J. Air & Waste Manage. Assoc. 63 (6): 724-736.

PMID- 24282963
TI  - Response to comments by Edward Nam, Ph.D., on "Accounting for acceleration and
      deceleration emissions in intersection dispersion modeling using MOVES and
      CAL3QHC".

PMID- 24282964
TI  - Estimating the concentration of indoor particles of outdoor origin: a review.
AB  - Recent toxicological results highlight the importance of separating exposure to
      indoor- and outdoor-generated particles, due to their different physicochemical
      and toxicological properties. In this framework, a number of studies have
      attempted to estimate the relative contribution of particles of indoor and
      outdoor origins to indoor concentrations, using either statistical analysis of
      indoor and outdoor concentration time-series or mass balance equations. The aim
      of this work is to review and compare the methodologies developed in order to
      determine the ambient particle infiltration factor (F(INF)) (i.e., the fraction
      of ambient particles that enter indoors and remains suspended). The different
      approaches are grouped into four categories according to their methodological
      principles: (1) steady-state assumption using the steady-state form of the mass
      balance equation; (2) dynamic solution of the mass balance equation using complex
      statistical techniques; (3) experimental studies using conditions that simplify
      model calculations (e.g., decreasing the number of unknowns); and (4)
      infiltration surrogates using a particulate matter (PM) constituent with no
      indoor sources to act as surrogate of indoor PM of outdoor origin. Examination of
      the various methodologies and results reveals that estimating infiltration
      parameters is still challenging. The main difficulty lies in the separate
      calculation of penetration efficiency (P) and deposition rate (k). The values for
      these two parameters that are reported in the literature vary significantly.
      Deposition rate presents the widest range of values, both between studies and
      size fractions. Penetration efficiency seems to be more accurately calculated
      through the application of dynamic models. Overall, estimates of the infiltration
      factor generated using dynamic models and infiltration surrogates show good
      agreement. This is a strong argument in favor of the latter methodology, which is
      simple and easy to apply when chemical speciation data are available.

PMID- 24282965
TI  - Comparison of physicochemical parameters during the forced-aeration composting of
      sewage sludge and maize straw at different initial C/N ratios.
AB  - The composting of sewage sludge and maize straw was investigated in forced
      aeration composting systems at initial C/N ratios of 14, 20, and 25,
      respectively. The temperatures of composting mixture with initial C/N ratios of
      25 and 20 could meet the requirement of destroying pathogens. The final
      electrical conductivity (EC) of composting mixture with initial C/N ratios of 20
      and 25 did not exceed the limit value of 3000 microS cm(-1), and the NH4(+)-N
      content of composting mixture with an initial C/N ratio of 14 did not meet the
      limit value of 400 mg kg(-1). The final NO3(-)-N and germination index (GI) of
      composting mixture with an initial C/N ratio of 25 were higher than those of
      composting mixtures with initial C/N ratios of 14 and 20. The Fourier transform
      infrared (FTIR) spectra of composting mixtures in the three composting mixtures
      showed the same changing pattern during the composting.

PMID- 24282966
TI  - Pyrolysis and gasification-melting of automobile shredder residue.
AB  - Automobile shredder residue (ASR) from end-of-life vehicles (ELVs) in Korea has
      commonly been disposed of in landfills. Due to the growing number of scrapped
      cars and the decreasing availability of landfill space, effective technology for
      reducing ASR is needed. However ASR is a complex mixture, and finding an
      appropriate treatment is not easy on account of the harmful compounds in ASR.
      Therefore, research continues to seek an effective treatment technology. However
      most studies have thus far been performed in the laboratory, whereas few
      commercial and pilot studies have been performed. This paper studies the
      pyrolysis and gasification-melting of ASR. The pyrolyis characteristics have been
      analyzed in a thermogravimetric analyzer (TGA), a Lindberg furnace, and a fixed
      bed pyrolyzer to study the fundamental characteristics of ASR thermal conversion.
      As a pilot study, shaft-type gasification-melting was performed. High-temperature
      gasification-melting was performed in a 5000 kg/day pilot system. The gas yield
      and syngas (H2 and CO) concentration increase when the reaction temperature
      increases. Gas with a high calorific value of more than 16,800 kJ/m3 was produced
      in the pyrolyzer. From the gasification-melting process, syngas of CO (30-40%)
      and H2(10-15%) was produced, with 5% CH4 produced as well. Slag generation was
      17% of the initial ASR, with 5.8% metal content and 4% fly ash. The concentration
      of CO decreases, whereas the H2, CO2, and CH4 concentrations increase with an
      increase in the equivalence ratio (ER). The emission levels of dioxin and air
      pollution compounds except nitrogen oxides (NO(x)) were shown to satisfy Korean
      regulations.

PMID- 24282967
TI  - C5-C12 volatile organic compounds at roadside, residential, and background
      locations in Ankara, Turkey: temporal and spatial variations and sources.
AB  - Concentrations of 91 volatile organic compounds (VOCs) ranging from C5 to C12
      were measured at three sites in Ankara, the capital of Turkey, in the summer of
      2003 and winter of 2004. Samples were collected at roadside, residential and
      background stations at consecutive 4-hr intervals over a 24-hr period for six
      weeks in each season. Air samples were collected onto cartridges packed with
      Tenax TA and Carbopack B resins and analyzed by thermal desorption, followed by
      gas chromatography coupled to a mass selective detector (GC/MSD). Time resolved
      data provided information on ambient levels, temporal and spatial variations and
      sources of VOCs in Ankara. Toluene is the most abundant compound at all sites
      with and average concentration of 13.1 ?g m(-3). The mean concentrations of
      benzene are 12.6, 5.2, and 2.4 ?g m(-3) during winter at roadside, residential
      and background stations, respectively. Diurnal variation in the data together
      with toluene to benzene concentration ratio (T:B) that is close to 2.0 indicated
      the influence of traffic related emissions at residential and roadside stations
      during winter season. Higher T:B ratio observed at residential and background
      stations during summer period and correlation analysis indicated additional VOC
      sources. Temporal variations and low m,p-xylene to ethylbenzene ratio (mpX:E)
      indicated that transported air mass is the major VOC source influencing VOC
      concentrations measured at the background station.

PMID- 24282968
TI  - Performance of commercial nonmethane hydrocarbon analyzers in monitoring
      oxygenated volatile organic compounds emitted from animal feeding operations.
AB  - Quantifying non-methane hydrocarbons (NMHC) from animal feeding operations (AFOs)
      is challenging due to the broad spectrum of compounds and the polar nature of the
      most abundant compounds. The purpose of this study was to determine the
      performance of commercial NMHC analyzers for measuring volatile organic compounds
      (VOCs) commonly emitted from AFOs. Three different NMHC analyzers were tested for
      response to laboratory generated VOCs, and two were tested in the field at a
      commercial poultry facility. The NMHC analyzers tested included gas
      chromatography/flame ionization detector (GC/FID), photoacoustic infrared (PA-IR)
      and photoionization detector (PID). The GC/FID NHHC analyzer was linear in
      response to nonpolar compounds, but detector response to polar oxygenated
      compounds were lower than expected due to poor peak shape on the column. The PA
      IR NMHC instrument responded well to the calibration standard (propane),
      methanol, and acetone, but it performed poorly with larger alcohols and ketones
      and acetonitrile. The PA-IR response varied between compounds in similar compound
      classes. The PID responded poorly to many of the most abundant VOCs at AFOs, and
      it underreported alcohols by > 70%. In the field monitoring study, total NMHC
      concentrations were calculated from sum total of VOC determined using EPA Methods
      TO-15 and TO-17 with GC-MS compared to results from NMHC analyzers. NMHC GC/FID
      values were greater than the values calculated from the individual compound
      measurements. This indicated the presence of small hydrocarbons not measured with
      TO-15 or TO-17 such as propane. The PA-IR response was variable, but it was
      always lower than the GC/FID response. Results suggest that improved approaches
      are needed to accurately determine the VOC profile and NMHC emission rates from
      AFOs.

PMID- 24282969
TI  - Characteristic analysis for odor gas emitted from food waste anaerobic
      fermentation in the pretreatment workshop.
AB  - Gas chromatography-mass spectrometry, olfactometry, and other related methods
      were applied for the qualitative and quantitative analysis of the characteristics
      of odorous gases in the pretreatment workshop. The composition of odorous gases
      emitted from municipal food waste was also investigated in this study. The
      results showed that the tested gases are mainly composed of aromatic gases, which
      account for 49% of the total volatile organic compounds (VOC) concentrations. The
      nitrogenous compounds comprise 15% of the total concentration and the other gases
      comprise the remaining 36%. The level of odor concentration ranged from 2523 odor
      units (OU) m(-3) to 3577 OU m(-3). The variation of the total chemical
      composition ranged from 19,725 microg m(-3) to 24,184 microg m(-3). Among the
      selected four sampling points, the discharge outlet was detected to have the
      highest concentration in terms of odor, total chemical, sulfur compounds, and
      aromatics. The correlation analysis showed that the odor concentrations were
      evidently related to the total chemical composition, sulfur compounds, and
      aromatics (P < 0.05, n = 5). The odor activity value analysis identified the top
      three compounds, hydrogen sulfide (91.8), ethyl sulfide (35.8), and
      trimethylamine (70.6), which contribute to air pollution complaint of waste
      materials.

PMID- 24282970
TI  - Evaluation of effect of reducing additives during vitrification via simulation
      and experiment.
AB  - This study investigates how reducing additives governed the vitrification of
      prepared specimens. In the experiments, pure CaO/CaCO3 and SiO2 served as the
      major components of glassy matrix (basicity = mass ratio of CaO/SiO2 = 2/3) with
      doping of hazardous metals (Cr Cu, and Ni). The substitution ratio of CaCO3 for
      CaO was used as an operating parameter. The specimens were vitrified at 1400
      degrees C and a sequential extraction protocol was used to determine the phase
      distribution of Cr, Cu, and Ni. The volume fractions of crystalline and amorphous
      phases were measured using semiquantitative x-ray diffraction (XRD) analysis. A
      commercial software package (HSC Chemistry 6.0) was used to simulate the
      experiment to acquire additional information. The simulation results showed the
      addition of CaCO3 generated CO and CO2 at high temperature. This reducing
      atmosphere might enhance Cu and Ni to be easily separated from slags and elevated
      the levels of Cu and Ni in ingots. At higher CaCO3 mol(%), the polymerization of
      silicate (from sorosilicate to inosilicate) in slag rose and the CaSiO3 amount
      increased. In addition, the immobilization of metals and the acid resistance of
      slags were improved. The results indicate that CaCO3 addition is favorable for
      increasing the metal level in ingots and the metal encapsulation in slag in
      vitrification.

PMID- 24282972
TI  - Carbon nanotubes among diesel exhaust particles: real samples or contaminants?
AB  - During three separate studies involving characterization of diesel particulate
      matter carbon nanotubes (CNTs) were found among diesel exhaust particles sampled
      onto transmission electron microscopy (TEM) grids. During these studies, samples
      were collected from three different diesel engines at normal operating conditions
      with or without an iron catalyst (introduced as ferrocene) in the fuel. This
      paper is to report the authors' observation of CNTs among diesel exhaust
      particles, with the intent to stimulate awareness and further discussion
      regarding the formation mechanisms of CNTs during diesel combustion.

PMID- 24282971
TI  - Monitoring total endotoxin and (1 --> 3)-beta-D-glucan at the air exhaust of
      concentrated animal feeding operations.
AB  - Mitigation of bioaerosol emissions from concentrated animal feeding operations
      (CAFOs) demands knowledge of bioaerosol concentrations feeding into an end-of
      pipe air treatment process. The aim of this preliminary study was to measure
      total endotoxin and (1 --> 3)-beta-glucan concentrations at the air exhaust of 18
      commercial CAFOs and to examine their variability with animal operation type
      (swine farrowing, swine gestation, swine weaning, swine finishing, manure belt
      laying hen, and tom turkey) and season (cold, mild, and hot). The measured
      airborne concentrations of total endotoxin ranged from 98 to 23,157 endotoxin
      units (EU)/m3, and the airborne concentrations of total (1 --> 3)-beta-D-glucan
      ranged from 2.4 to 537.9 ng/m3. Animal operation type in this study had a
      significant effect on airborne concentrations of total endotoxin and (1 --> 3)
      beta-D-glucan but no significant effect on their concentrations in total
      suspended particulate (TSP). Both endotoxin and (1 --> 3)-beta-D-glucan attained
      their highest airborne concentrations in visited tom turkey buildings.
      Comparatively, season had no significant effect on airborne concentrations of
      total endotoxin or (1 --> 3)-beta-D-glucan. Endotoxin and (1 --> 3)-beta-glucan
      concentrations in TSP dust appeared to increase as the weather became warmer, and
      this seasonal effect was significant in swine buildings. Elevated indoor
      temperatures in the hot season were considered to facilitate the growth and
      propagation of bacteria and fungi, thus leading to higher biocomponent
      concentrations in TSP.

PMID- 24282973
TI  - Airborne bacterial reduction by spraying slightly acidic electrolyzed water in a
      laying-hen house.
AB  - Spraying slightly acidic electrolyzed water (SAEW) has been considered as a
      potential approach to reduce airborne bacteria in laying-hen houses. In this
      study, the effects of spraying SAEW on airborne bacterial reduction were
      investigated in a laying-hen house as compared with using diluted didecyl
      dimethyl ammonium bromide (DDAB). Averaged air temperature reduced by approximate
      1 degrees C and average relative humidity increased by 3% at a stable ventilation
      rate (about 2.5 m3 hr(-1) per bird) in the laying-hen house 30 min after spraying
      (120 mL m(-2)). Compared with the control without spraying, the airborne
      bacterial concentration was reduced by about 0.70 and 0.37 log10 colony-forming
      units (CFU) m(-3) in the 4 hr after spraying 120 mL m(-2) SAEW (available
      chlorine concentration [ACC] of 156 mg L(-1)) and diluted DDAB (active compound
      concentration of 167 mg L(-1)), respectively. Compared with spraying diluted
      DDAB, spraying SAEW was determined to be more effective for reducing airborne
      bacterial in laying-hen houses. The effects of spraying SAEW and diluted DDAB on
      airborne bacterial reduction in the laying-hen house increased with the
      increasing available chlorine concentrations for SAEW (156, 206, 262 mg L(-1))
      and increasing active compound concentrations for diluted DDAB (167, 333, 500 mg
      L(-1)), respectively. Spraying SAEW and diluted DDAB with two levels of spraying
      volumes (120 and 90 mL m(-2)) both showed significant differences on airborne
      bacterial reduction in the laying-hen house (P < 0.05).

PMID- 24282974
TI  - Comparison of on-road emissions for hybrid and regular transit buses.
AB  - Hybrid technology offers an attractive option for transit buses, since it has the
      potential to significantly reduce operating costs for transit agencies. The main
      impetus behind use of hybrid transit vehicles is fuel savings and reduced
      emissions. Laboratory tests have indicated that hybrid transit buses can have
      significantly lower emissions compared with conventional transit buses. However
      the number of studies is limited and laboratory tests may not represent actual
      driving conditions, since in-use vehicle operation differs from laboratory test
      cycles. This paper describes an on-road evaluation of in-use emission differences
      between hybrid-electric and conventional transit buses for the Ames, Iowa transit
      authority, CyRide. Emissions were collected on-road using a portable emissions
      monitoring system (PEMS) for three hybrid and two control buses. Emissions were
      collected for at least one operating bus day. Each bus was evaluated over the
      same route pattern, which utilizes the same driver. The number of passengers
      embarking or disembarking at each stop was collected by an on-board data
      collector so that passenger load could be included. Vehicle emissions are
      correlated to engine load demand, which is a function of factors such as vehicle
      load, speed, and acceleration. PEMS data are provided second by second and
      vehicle-specific power (VSP) was calculated for each row of data. Instantaneous
      data were stratified into the defined VSP bins and then average modal emission
      rates and standard errors were calculated for each bus for each pollutant.
      Pollutants were then compared by bus type. Carbon dioxide, carbon monoxide, and
      hydrocarbon emissions were higher for the regular buses across most VSP bins than
      for the hybrid buses. Nitrogen oxide emissions were unexpectedly higher for the
      hybrid buses than for the control buses.

PMID- 24282975
TI  - Ozone sensitivity to its precursor emissions in northeastern Mexico for a summer
      air pollution episode.
AB  - A summer episode was modeled to address the expected response of ambient air O3
      to hypothetical emission control scenarios in northeastern Mexico, and in
      particular in the Monterrey Metropolitan Area (MMA). This region is of interest
      because the MMA holds one of the worst air quality problems in the country and
      levels of air pollutants in the rest of northeastern Mexico are starting to be a
      concern. The MM5-SMOKE-CMAQ platform was used to conduct the numerical
      experiments. Twenty-four control scenarios were evaluated, combining the level of
      emission controls of O3 precursors (NO(x) and volatile organic compounds [VOCs])
      from 0% to 50%. For the MMA, VOC-only controls result in the best option to
      reduce O3 concentrations, though the benefit is limited to the urban core. This
      same strategy results in negligible benefits for the rest of northeastern Mexico.
      NO(x) controls result in an increase in O3 concentration within the MMA of up to
      20 ppbv and a decrease at downwind locations of up to 11 ppbv, with respect to
      the base-case scenario. Indicator ratios were also used to probe for NO(x)
      sensitive and VOC-sensitive areas. Locations with an important influence of NO(x)
      point sources (i.e., Monclova and Nava/Acuna) are quite sensitive to changes in
      NO(x) emissions. Border cities in the Rio Bravo/Grande Valley tend to be
      marginally NO(x)-sensitive. Overall, the MMA seems to be dominated by a VOC
      sensitive regime, while the rest of the region would tend to have a NO(x)
      sensitive response. The results obtained serve to expand the current knowledge on
      the chemical regimes that dominate this region (VOC- or NO(x)-sensitive), and
      thus could help guide public policies related to emission regional control
      strategies.

PMID- 24282976
TI  - Advancing patient-centric genomic medicine.

PMID- 24282977
TI  - Management of marginal zone lymphoma.

PMID- 24282978
TI  - New targets for triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) lacks the three most commonly targeted
      receptors in human breast cancer--the estrogen receptor (ER), progesterone
      receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu--and it is
      associated with an aggressive natural history. More recently, TNBC has been
      further dissected into smaller, distinct subsets with unique molecular
      alterations and response to therapy. Large-scale genomic projects have yielded
      new knowledge about the molecular characteristics of TNBC, including similarities
      with high-grade serous ovarian cancers, suggesting a possible coordinated
      treatment algorithm for these malignancies. Moreover, translation of preclinical
      findings has led to clinical trials testing a plethora of targets and pathways in
      TNBC, which will be reviewed here; these include epidermal growth factor receptor
      (EGFR), angiogenesis, DNA repair capacity, epigenetic regulation, androgen
      receptor (AR) and folate receptor (FR) signaling, cell-cycle control, and cell
      survival. Given the complexity of TNBC biology and the lack of "traditional"
      therapeutic targets, the advancement of care for women with TNBC will require a
      true partnership between clinicians, translational investigators, and basic
      scientists.

PMID- 24282979
TI  - Triple-negative breast cancer: not entirely negative.

PMID- 24282980
TI  - Triple-negative breast cancer in the post-genomic era.

PMID- 24282981
TI  - Oral oncolytics: Part 2--legislation targeting cost & access, and other
      initiatives to reduce costs.

PMID- 24282982
TI  - T1 high-grade bladder cancer recurring after BCG therapy: radical cystectomy is
      still the best approach. Pro.

PMID- 24282983
TI  - T1 high-grade bladder cancer recurring after BCG therapy: a curative alternative
      to radical cystectomy exists. Con.

PMID- 24282984
TI  - Peripheral T-cell lymphoma: new therapeutic strategies.
AB  - Between 2006 and 2011, four new agents gained regulatory approval for the
      treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) and peripheral
      T-cell lymphoma (PTCL). These new approvals, together with recent advances in
      both combination chemotherapy and transplant strategies, have made the landscape
      for treatment of these patients immensely complex. Multiple clinical trials are
      now underway, evaluating the role of combining new agents with existing drugs and
      regimens, both for untreated and relapsed/refractory CTCL and PTCL. Pending
      results of such trials, clinicians are generally left with incomplete data and
      competing therapies when tasked with the treatment of these patients. In this
      article, we will briefly review the labeled indications for new agents for CTCL
      and PTCL, but will focus on data from the last 1 to 2 years, and on data from
      ongoing clinical trials, with the hope that in doing so we can help elucidate
      difficult treatment decisions.

PMID- 24282985
TI  - Peripheral T-cell lymphoma: time for a T-cell-centric standard of care.

PMID- 24282986
TI  - Peripheral T-cell lymphoma: what's the role for transplant?

PMID- 24282987
TI  - Collision renal cell papillary and medullary carcinoma in a 66-year-old man.

PMID- 24282988
TI  - Clinical applications of The Cancer Genome Atlas project (TCGA) for squamous cell
      lung carcinoma.
AB  - Very little progress has been made in the treatment of patients with metastatic
      squamous cell lung cancer over the past 2 decades. Identification of novel
      molecular alterations for targeted therapies is necessary to improve outcomes.
      Advances in genomic technology have now made it possible to analyze the genomic
      landscape of tumor tissues comprehensively. We summarize here key findings from
      the comprehensive analysis of squamous cell lung cancer by The Cancer Genome
      Atlas group and discuss the clinical implications of these findings.

PMID- 24282989
TI  - Do oncogenic drivers exist in squamous cell carcinoma of the lung?

PMID- 24282990
TI  - Squamous cell lung cancer: where do we stand and where are we going?

PMID- 24282991
TI  - The F-word.

PMID- 24282992
TI  - "I'm the decider! (is that OK with you?)".

PMID- 24282993
TI  - Non-secretory myeloma: a clinician's guide.
AB  - The treatment of patients with multiple myeloma has dramatically changed over the
      past 10 years due to an improved understanding of plasma cell biology and the
      development of new targets. The subset of these patients with non-secretory
      myeloma-a group of patients who do not secrete immunoglobulin or its component
      parts into either the blood or urine-has been challenging to treat and to assess
      for disease response. Newer methods of assessment for plasma cell disorders, such
      as the widely used serum free light chain assay, have reduced the number of
      patients with truly non-secretory myeloma to less than 3% of all newly diagnosed
      myeloma patients. With regard to prognosis, it appears from most series that
      patients with non-secretory myeloma have a prognosis similar to or better than
      that of patients with secretory myeloma.This has not been evaluated in
      populations from which patients with free light-only disease are excluded, but
      there is no reason to expect that outcomes in patients with non-secretory myeloma
      will be appreciably worse, since many harbor the t(11;14) translocation. Finally,
      imaging with positron emission tomography (PET)/CT scans, and minimal residual
      disease (MRD) assessment with multi-parameter flow cytometry, may provide newer
      methods for response assessment, something that has been severely limited in
      these patients due to the lack of a reliable biomarker. Future directions in
      response assessment include the amalgamation of imaging and MRD assessment, which
      may enhance our ability to assess response both in patients with non-secretory
      myeloma and in other patients with myeloma.

PMID- 24282994
TI  - Non-secretory myeloma: one, two, or more entities?

PMID- 24282995
TI  - Non-secretory myeloma: clinical and biologic implications.

PMID- 24282996
TI  - Developing a community care team: lessons learned from the community connections
      program, a health care home-community care team partnership.
AB  - This article describes the development of the Community Connections Program
      (CCP), a community care team, within a health care home (HCH), as a short-term,
      intensive, team-based service planning and coordination program for older adults
      with multiple chronic health conditions. Three proven approaches were combined to
      support patient's self-management, nurse care coordination, the Wraparound
      process, and use of community services. Particzpants'responses to the CCP
      demonstrated the success of the community care team in connecting patients and
      nurse care coordinators (NCCs) with community service providers, thus supplying
      primary care providers with important information regarding the development of a
      community care team to support patient-centered care within a HCH.

PMID- 24282997
TI  - Mental health, suicide, and self-centered behavior: focus on the japanese family
      and the elderly.
AB  - My mother-in-law is very selfish because she has been living alone for a long
      time. She is so used to living alone that she thinks nothing of doing things like
      vacuuming at midnight. My mother-in-law only talks about herself and doesn't seem
      very interested in her son or what other people say or are doing. This makes it
      difficult to interact and communicate with her. I do not want to take care of my
      mother-in-law should she become ill and this is something I think about, since my
      husband is the eldest son.

PMID- 24282998
TI  - Sally Levy. Interview by Marian Brickner.

PMID- 24282999
TI  - Continuing to work toward a convention on the rights of older persons.

PMID- 24283000
TI  - Meeting Hurricane Sandy head-on: New York City's aging services network delivers
      in a crisis.

PMID- 24283001
TI  - New York's Medicare Marketplace: examining new York's Medicare advantage plan
      landscape in light of payment reform.
AB  - The Patient Protection and Affordable Care Act (ACA) provided for cost savings in
      the Medicare program, in part to underwrite coverage expansion to Medicare
      beneficiaries, to finance new coverage for those not eligible for Medicare, and
      to strengthen Medicare's financial outlook. One cost-saving measure, a
      reformulation and reduction in payments to private health insurance plans that
      provide Medicare benefits through the Medicare Advantage (MA) program, had a
      sound policy basis but was criticized, particularly by opponents o fthe ACA, as a
      measure that would lead to increased costs, reductions in benefits, and
      diminished plan choices to Medicare beneficiaries enrolled in MA plans. Despite
      dire predictions to this effect, a review of a sample of MA plan offerings in New
      York State in 2012 shows that Medicare beneficiaries enrolled in such plans did
      not experience significant benefit reductions or increased costs. While the
      number of plan offerings decreased, the reduction was mostly caused by the
      elimination of duplicative plan choices in 2011. Although the MA plan executives
      we interviewed indicated that further reductions in plan reimbursement in future
      years-tempered by potential bonus payments for meeting quality and performance
      metrics-could impact plan costs and benefits, they believed plans will employ a
      number of strategies to remain in the market and maintain benefciary benefits and
      cost structures. However, government regulators and consumer advocates will need
      to examine MA plan offerings in the coming years to determine the efect ofplan
      reaction to the ACA payments on beneficiaries'costs for coverage and access

PMID- 24283002
TI  - A cross-national comparison of perceptions of aging and older adults, part 3.

PMID- 24283003
TI  - For love, legacy, or pay: legal and pecuniary aspects of family caregiving.
AB  - Most caregiving and companionship provided by family members and friends to older
      individuals in home environments occurs because of the caregiver's feelings of
      ethical and emotional obligation and attachment. From a legal perspective,
      though, it might be ill-advised for an informal caregiver to admit such a
      motivation. Building on a recently published study of relevant litigation, this
      essay discusses changing cultural and legal aspects of family caregiving when
      there is some expectation of pay, property, or fuiture financial legacy in return
      for the caregiver's present work and sacrifices.

PMID- 24283004
TI  - Data glitches are hazardous to your health.

PMID- 24283005
TI  - Manufacturing, Hollywood-style.

PMID- 24283007
TI  - Sayonara, supergiant.

PMID- 24283006
TI  - A new race to earth's end.

PMID- 24283008
TI  - What's better than BMI?

PMID- 24283009
TI  - Mutating viruses lead cops to the criminals.

PMID- 24283010
TI  - Gambling on the brain.

PMID- 24283011
TI  - Crash text dummies.

PMID- 24283012
TI  - King of beasts.

PMID- 24283013
TI  - Worlds with two suns.

PMID- 24283014
TI  - Why the brain prefers paper.

PMID- 24283015
TI  - Hacking drones.

PMID- 24283017
TI  - How should we think about privacy? Making sense of one of the thorniest issues of
      the digital age.

PMID- 24283016
TI  - The long trail of cancer's clues.

PMID- 24283018
TI  - What if we could tap vast deposits of methane-rich brine deep beneath the ocean
      and use the energy to cut carbon emissions?

PMID- 24283019
TI  - Sovereign insanity; how weird beliefs can land you in jail.

PMID- 24283020
TI  - Old age ... lessness.

PMID- 24283021
TI  - Where is dentistry going?

PMID- 24283022
TI  - A dentist's guide to the National Practitioner Data Bank.

PMID- 24283023
TI  - Encourage your employees to give back.

PMID- 24283024
TI  - Dentistry's cancer.

PMID- 24283025
TI  - Know the facts about oral cancer.

PMID- 24283026
TI  - A glass of milk after eating sugary cereals may prevent cavities.

PMID- 24283027
TI  - You might say they're 'kissin' cousins'.

PMID- 24283028
TI  - Moral incontinence.

PMID- 24283029
TI  - Writing off copayments.
AB  - Professions are accorded respect and autonomy by society in exchange for their
      willingness to enforce their own professional standards. A case is discussed
      where an associate discovers that the principal dentist is routinely not
      collecting the 20% copayment required by insurance contracts. Analysis shows that
      this practice is unethical, illegal, and unprofessional. Practical advice is
      offered for how such an issue should be addressed.

PMID- 24283030
TI  - Domestic violence dilemma in the dental clinic.
AB  - A case is presented where a dentist recognizes physical abuse of a patient.
      Although legally the dentist must report such cases, the patient asks that this
      not be done. Statistics are presented regarding the prevalence and consequences
      of abuse, and one potential response is suggested.

PMID- 24283031
TI  - Culturally diverse patients and professionalism in dentistry.
AB  - A case is considered in which the father of an adult patient from another culture
      requests that only limited care be provided his daughter. Additional indicated
      treatment was declined. The patient appeared to defer to her father as a cultural
      norm. Various ethical principles and the conflicts among them are considered in
      light of cultural competency.

PMID- 24283032
TI  - College students practice dentistry in third-world countries.
AB  - Increasingly, applicants to dental schools are reporting experiences providing
      dental care on third-world mission trips. Perhaps they do not know that this
      behavior is unethical and illegal, but those directing and sponsoring these
      programs could not so easily claim to be unaware that what they are doing is
      wrong. Policy statements and informational campaigns by professional
      organizations may help curb this abuse.

PMID- 24283033
TI  - Ethical considerations of randomized control trials with human participants in
      dentistry. A reflective analysis.
AB  - A potential conflict is built into the roles of dentists and researchers with
      regard to ethical principles such as beneficence, nonmaleficence, respect for
      autonomy, and justice. The practitioner has an obligation to do what is believed
      to be best for the individual patient: the dentist as researcher has an
      obligation to use rigorous experimental methods, including randomized control
      trials (RCTs) to discover what is best for patients generally, including the
      investigation of experimental modalities. This is the equipoise problem-how can a
      professional be assured of offering the most beneficial treatment available if
      only using approaches that have worked in the past? This essay explores the
      ethical foundations for this challenge and proposes a groundwork for balancing
      ethical obligations to patients and the needs for scientific and public health
      advances.

PMID- 24283034
TI  - Thinking in a straight line.
AB  - Rational human discourse is not as common as we imagine or as we would like it to
      be. Sometimes it is necessary to use fallacies and fabrication to get to the
      point we favor. This essay is an illustrated list of 33 handy tools for avoiding
      thinking straight.

PMID- 24283035
TI  - [A new classification of hiatal hernias, based on analysis of far remote results
      of laparoscopic plasty].
AB  - The results of operative treatment of 787 patients, suffering hiatal hernia (UH),
      were analyzed. Depending on the hiatal foramen square the patients were divided
      into three groups: with a small, large and giant hernias. In large HH a
      cruroraphy conduction causes a trustworthy more recurrence rate, than in small
      HH. In large HH the alloplasty performance secures lesser recurrence rate, then
      in cruroraphy conduction, although the dysphagia rate is bigger. While performing
      original method the dysphagia rate is minimal in comparison with such, when
      polypropylene transplant is used for plasty. In a giant HH alloplasty is
      complicated by trustworthy enhanced recurrence rate (19%), than in large HH,
      trusting neccessity to elaborate a new methods of correction. Basing on results
      of a factorial analysis made, concerning an accordance of the hiatal defect
      square with the recurrence rate in the groups of patients, there was established,
      that the division levels (10 and 20 cm2) for establishing the HH classification
      strictly parallels the recurrence rate in each class determined by the authors.

PMID- 24283036
TI  - [A complex method for prophylaxis of laparoscopic cholecystectomy complications].
AB  - The clinical examination and treatment results were analyzed in 1282 patients, in
      whom laparoscopic cholecystectomy, using complex method of the complications
      prophylaxis, was performed for calculous cholecystitis. The complications have
      had occurred in 21 (1.64%) patients, the conversion necessity--in 10 (0.78%), 3
      (0.23%) patients died.

PMID- 24283037
TI  - [The modern approach to endoscopic drainage of pancreatic pseudocysts].
AB  - The results of endoscopic surgical procedures performed in 72 patients over
      postnecrotic pseudocysts (PPC) of the pancreas. Complications occurred in 9
      (12.5%) patents, recurrence PPC pancreas after endoscopic procedures were
      observed in 6 (8.3%).

PMID- 24283038
TI  - [Differentiated approach to the choice of the treatment method for pancreatic
      pseudocysts].
AB  - The results of treatment of 182 patients, suffering pancreatic pseudocysts, were
      analyzed. Total of 226 operative interventions were performed. Under
      ultrasonographic control 142 (78.02%) patients were operated, open surgical
      procedures were conducted in 68 (37.36%) patients. While doing selection of the
      operative intervention method it is mandatory to take into account not only the
      size and character of the cyst, but the pancreatic parenchyma and ductal system
      state, as well as the presence of complications. Application of a puncture
      draining method in the pancreatic cysts treatment, which have originated after an
      acute pancreatitis, is effective in 71.08%, owes low of complications 2.41% and
      lethality 0.98%. While the pancreatic cysts treatment, which have developed as a
      consequence of chronic pancreatitis exacerbation, application of the cysts
      draining under ultrasonographic control is effective in 57.89% of the cases, and
      is performed in 15.80% as a first stage to stabilize the patient state and his
      preoperative preparation, correcting the signs of chronic pancreatitis and were
      conducted in our observations in 36.84% of patients. While the cysts are
      formatted on a chronic pancreatitis background practically all the gland becomes
      affected by chronic inflammatory process with degenerative-cystic transformation
      of pancreatic parenchyma, calculous changes and ductal hypertension. The
      resectional and resection-draining operations, which were performed in 57.14% of
      patients, have had constituted the method of choice in the treatment of
      pancreatic pseudocysts.

PMID- 24283039
TI  - [Experience of ASVS-test application in diagnosis of insulin-producing pancreatic
      tumor].
AB  - In 2009-2013 yrs in 7 patients, suffering insulin-producing pancreatic tumors,
      the ASVS-test was conducted, the result of which was compared with data of
      standard methods of investigation, including abdominal ultrasound, computer
      tomography and magnetic resonance imaging. The insuloma enucleation was performed
      in 3 patients, distal subtotal pancreatectomy with splenectomy--in 1 and the
      completed total pancreatectomy--in 1. The ASVS-test conduction is indicated in
      patients with diagnosed hyperinsulinism while impossibility to perform a topic
      diagnosis of insulinoma, in accordance to data of other noninvasive methods of
      diagnosis.

PMID- 24283040
TI  - [Combined laparoscopic operations in patients with acute appendicitis and biliary
      calculous disease].
AB  - The experience of surgical treatment was summarized in patients, suffering an
      acute appendicitis, in whom simultaneously a biliary calculous disease was
      revealed. The procedure and technical aspects of performance of simultant
      laparoscoplic operation were depicted, the indications and contraindications for
      simultant operation conduction were determined, a consequence of the operative
      stages performance was determined. The main advantages of simultant laparoscopic
      operations were proved and the results of treatment analyzed.

PMID- 24283041
TI  - [Prognostication of acute-pancreatitis-associated pulmonary injury based on
      determination of cytokines levels].
AB  - The results of examination of 68 patients, admitted to hospital for an acute
      pancreatitis during 48 h from its occurrence, were analyzed. In all the patients
      the cytokines (IL-8, IL-10, TNF-alpha) content was determined in the blood, using
      immunoenzymal analysis. Algorithm of prognostication of an acute pancreatitis
      associated pulmonary injury, basing on determination of the cytokines contents,
      was elaborated.

PMID- 24283042
TI  - [Clinico-prognostic analysis of course of thyroid medullary carcinoma].
AB  - Analysis of localization, character of development, sizes and metastatic
      potential of tumors in patients, suffering various forms of thyroid medullary
      carcinoma (THMC), was accomplished, permitting to establish a certain dependence
      of these characteristics from the recurrence occurrence frequency and lethality
      in groups of patients, owing different gender. The tumor diameter more than 2 cm
      and presence of metastases in time with diagnosis establishing have constituted
      the unfavorable factors, causing lethality enhancement in sporadic form of THMC.
      In women patients more frequent multifocal development coincide with lesser
      frequent metastasizing and lesser lethality in comparison with such in men.
      Lethality in men in sporadic form of THMC is twice as more, than in women
      patients, and it is explained by tumor diagnosis in them in later stages,
      although their postoperative life span is longer, taking into account the
      unfavorable impact of intraoperative age (bigger, than in men) on the results of
      treatment and prognosis. Lethality in inherited forms of THMC is significantly
      lesser, than in sporadic form, independently from impact of such existing
      factors, as more frequent multifocal tumor development, bilateral thyroid
      affection and similar frequency of metastasizing. In men the metastasizing is
      occurring more frequently, as it take place in cases of a sporadic form of the
      disease, causing higher lethality in them, comparing with such in women,
      suffering inherited forms of THMC.

PMID- 24283043
TI  - [Prognostic significance of p53 expression in patients with mammary gland
      cancer].
AB  - Prognostic significance of p53 expression in tumoral cells was studied in
      patients, suffering mammary gland cancer (MGC). The higher p53 mutative type
      expression in the tumor, the more aggressive is MGC development, the indices of
      general and disease-free survival are poorer, so prognosis is poorer as well.

PMID- 24283044
TI  - [Efficacy of a high-power laser vaporization in comparison with a monopolar
      transurethral resection in the treatment of benign prostatic hyperplasia: results
      of a 6-months follow-up].
AB  - Prospective investigation was conducted in 120 patients, operated on for benign
      prostatic hyperplasia, including 60--using transurethral prostatic resection
      (TUPR), and in 60--fotoselective vaporization (FSV). The operation duration was
      shorter while the TUPR application--(62 +/- 13) min than in FSV--(89 +/- 18) min.
      Although, duration of catheterization in FSV have had constituted at average (1.4
      +/- 0.6) days and in TUPR--(3.0 +/- 0.6) days; the hospital stay was less after
      FSV--at average (2.4 +/- 1.3) days, and after TUPR--(4.2 +/- 0.5) days.

PMID- 24283045
TI  - [Complex treatment of mandibular malignant tumors using a fixing device for
      prophylaxis of pathological fracture, the early postoperative prosthesis and
      rehabilitation].
AB  - Even in modern conditions of achievements in the head and neck oncosurgery the
      restoration of the volume defects of the bone tissue in a jaw-facial region is
      impossible to do without the orthopedic methods application because of present
      severe psychoemotional and general state of the patients. The problem of
      prophylaxis of mandibular pathological fractures in its malignant affection
      constitute a peculiar place, taking into account a complexity and numerousness of
      the unsolved issues. There was elaborated and constructed apparatus for the
      pathological fracture prophylaxis or for fixing of fragments in the angle of a
      toothless mandibula. After the apparatus being applied in place the patient's
      quality of life improves: they better tolerate radiation therapy; the conditions
      for surgical treatment are improving; the acts of chewing and deglutition are not
      disordered, what improves the patients state significantly; the general image of
      the face is not disturbed. The methods may be introduced into specialized
      clinics.

PMID- 24283046
TI  - [The inborn flat-valgus deformity of the foot in children].
AB  - To optimize the diagnosis and treatment for the inborn flat-valgus deformity of
      the foot (IFVDF), the results of treatment of 78 children, ageing from 1 mo to 12
      yrs old, were analyzed. Algorithms of diagnosis and treatment were elaborated.
      Operative treatment on soft tissues for IFVDF was indicated in the cases of
      inefficacy or insufficient efficacy of conservative therapy in the age after 1
      year old, when a child starts to walk by himself. The proposed method of
      operative treatment permits to achieve good results and it is less traumatic in
      comparison with the existing methods. Better results are noted while application
      of the method in children, ageing from 1 to 4 yrs old.

PMID- 24283047
TI  - [Practical application of a high-frequency coagulators with different
      electrophysical characteristics].
AB  - The results of experimental-clinical investigation on studying of technical
      characteristics and practical application of various types of electrocoagulators
      were adduced. Comparative analysis of possibility to perform the main stages of
      surgical interventions, using well-known apparatuses of various manufacturers,
      was conducted.

PMID- 24283048
TI  - [Effects of the umbilical blood stem cells in experimental injury of myocardium].
AB  - Morphological, functional signs of myocardium affection and tolerance to physical
      loading in animals with isoproterenol-induced affection of myocardium after
      transplantation of a nuclear-containing cells (NCC) of umbilical blood were
      analyzed in comparison with a natural course of the model. There was proved, that
      a transplantation of a NCC promotes acceleration of processes of regeneration and
      restoration of the damaged myocardium in experimental animals. There were
      estimated the changes in localization of the transplanted NCC in the zone of
      damage, and capacity of the peripheral blood NCC, while they were transplanted,
      using intravenous injection, to migrate into the damage zone. The experimental
      data obtained need further complex analysis and permit to wait a positive effect
      while performing clinical investigations in the patients, suffering chronic
      diseases of the heart.

PMID- 24283049
TI  - [Local impact of antiseptic medical textile on tissues of organism].
AB  - Morphological investigation for studying of a local impact on the tissues,
      localized in the antiseptic textile implantation zone, was conducted. The textile
      was impregnated by composition of decametoxine with modified polysaccharides.
      Basing on the investigation result there was established the absence of a toxic
      impact of antiseptic medical textile on the macroorganism tissues, the
      regenerative processes course, the wounds epithelization, antioedematous and anti
      inflammatory effects.

PMID- 24283050
TI  - [The stem cells and a problem of regeneration of peripheral nerves].

PMID- 24283051
TI  - [Duodenectomy with translocation of duodenal papilla magna for giant retroampulla
      ulcer].

PMID- 24283052
TI  - [Encephalomyelopathy in patients with acute necrotizing pancreatitis].

PMID- 24283053
TI  - [Observation of a successful endovascular correction of a false arterial aneurysm
      of a rare localization].

PMID- 24283054
TI  - [Conservative treatment of patients with critical ischemia of the lower
      extremities].

PMID- 24283055
TI  - [V Congress of Cardiovascular Surgeons of Ukraine and Poland "Actual Problems of
      Cardiovascular Surgery", dedicated to the 100th birthday of academician M. M.
      Amosov].

PMID- 24283056
TI  - [Fetal growth curve based on gestational age and fetal maturity].
AB  - Most of the fetal growth charts available in the literature were created too long
      ago, based on various populations and using various eligibility criteria. The
      purpose of our study was to develop a nomogram of fetal weights based on the
      gestational age and neonatal maturity. The study is prospective and retrospective
      in nature. 1,748 fetuses of 20 to 40 gestational weeks were assessed directly
      after birth, and all cases were classified based on the number of weeks of
      pregnancy completed, but fetuses were not classified based on their gender. The
      mean weekly weight gain of fetuses was 100 g until the 30 gestation week, and 200
      g thereafter. The results we obtained for the 50th percentile for fetus weight
      were weights meanly 200 g lower than those per Babson's chart (Fenton's scale).
      The weights in the 10th percentile were also 50-100 g lower until the 31
      gestation week, with increasing difference to 150 g thereafter. For 2011, the
      incidence of growth-retarded fetuses at Maichin Dom Hospital was 7.09% per
      Babson's chart, and 5.1% according to our data of the 10th percentile. The study
      demonstrated that nomograms for relevant populations should be used to assess
      normal growth of fetuses.

PMID- 24283057
TI  - [Diagnostic value of TruScreen, cytology and colposcopy].
AB  - The aim of this study was to compare the diagnostic value of TruScreen with that
      of already approved in practice methods for detection of precancerous conditions
      of the cervix. This study reviewed 301 patients; for analysis were included 260
      women aged from 16 to 69 years, mean 35.82 years. They were divided into three
      groups. RESULTS: After statistical analysis of the results we found sensitivity
      of conventional Pap smear, colposcopy and TruScreen respectively 67.44%, 96.55%
      and 53.85%, and specificity respectively 83.93%, 45.90% and 78.79%. CONCLUSION:
      TruScreen is a representative of real time methods for cervical screening. Our
      results are close to the obtained in other studies: medium value sensitivity and
      high specificity of the method, which shows that there is a possibility for its
      use as a primary screening, and also in addition to cytology. TruScreen is
      especially suitable in places where no cytology laboratories and specialists are
      available. It is a quick method (result at the moment), does not require special
      qualification and long training of the operator (as opposed to colposcopy) and is
      well received by women. Sufficient number of cases remains to be collected for
      more accurate assessment of the potential of TruScreen. It is appropriate to
      identify if TruScreen has different diagnostic value in mild and severe cervical
      changes, and also its efficacy as a primary screening method and in combination
      with other already approved in practice screening methods.

PMID- 24283058
TI  - [Efficacy of combined 5-nitroimidazole and probiotic therapy of bacterial
      vaginosis: randomized open trial].
AB  - The aim of the current research is to identify the clinical and microbiological
      effect of 5-nitroimidazol therapy for the treatment of bacterial vaginosis and in
      combination with probiotics and the influence of such therapy upon vaginal flora.
      MATERIALS AND METHODS: Women (n = 539) with bacterial vaginosis who meet the
      criteria were included in the study. They were randomized into two groups with
      the following therapeutic regimes: in the first group (n = 242 women) the
      treatment included applications of 2g BID tinidazole for two days and vaginal
      suppositories of 1000 mg metronidazol at day 1 and 3 (T+M). In the second group
      (n = 297) the women were cured with the same treatment as those in the first
      group. In addition to it from the fifth day of the treatment was added a topical
      administration of vaginal probiotic which contains species of alive lactobacilli:
      Lactobacillus acidophilus, Lactobacillus rhamnosus (T+M+P). The efficacy from the
      therapy was evaluated using the clinical compliances of the women, the data from
      the clinical examination and the microbiological tests results. RESULTS: The
      results showed expected increase of clinical therapy efficacy (Amsel - criteria)
      from 42.8% (T+M; n = 211/242) to 84.06% (T+M+P; n = 274/297) in groups and of
      microbiological efficacy (Nugent) from 44.7% (T+M; n = 211/242) to 83.3% (T+M+P;
      n = 274/297), in follow up 35-40 days from the beginning of treatment. The
      percentage of women with normal vaginal flora on 35-40 day after the therapy
      increase with 57% in the (T+M) first group while in the second group (T+M+P) with
      94%. CONCLUSIONS: Combining the therapies of 5-nitroimidazoles and vaginal
      probiotic reduce bacterial vaginosis recurrence and restores permanently normal
      vaginal flora.

PMID- 24283059
TI  - [Borderline ovarian tumours: a challenge for clinicians].
AB  - A retrospective analysis of surgical procedures for ovarian tumours, performed in
      the Department of General and Oncological Gynaecology at the Military Medical
      Academy (Sofia, Bulgaria) specified 81% of the tumour cases as benignant ones,
      15.6% as malignant ones, and 3.4% as borderline ovarian tumours (BOT). The
      histological type of BOT was assessed as serous in 62% and as mucinous in 38%.
      The incidence of BOT was found to increase with increasing age. Most patients
      with BOT were parous (60%). Serum levels of CA 125 were within normal values in
      all patients with BOT.

PMID- 24283060
TI  - [Prognostic significance of lymph node dissection in terms of overall survival of
      invasive cervical cancer].
AB  - OBJECTIVE: To establish the role of the lymph node dissection (LND) and the
      overall. Survival of patients with invasive cervical cancer depending on their
      lymph node status. MATERIAL AND METHODS: The follow-up period includes the date
      of registration until September 2011 or exitus letalis. (from 2 to 96 months,
      average 45 months). RESULTS: We presented the relationships between presense of
      lymph node metastases (LNM), number of LNM, localization of LNM, micro- and macro
      LNM and the overall survival of patients staged IB1 -IIB. CONCLUSION: Patients
      with microscopic LNM reveal similar overall survival (81%) to patients without
      LNM (86%). In these patients LND demonstrates therapeutic effect.

PMID- 24283061
TI  - [Blood lactate measurments as a diagnostic and prognostic tool after birth
      asphyxia in newborn infants with gestational age > or = 34 gestational weeks].
AB  - Blood lactate at birth as result of activated anaerobic glycolysis is a marker of
      perinatal asphyxia. AIM: To evaluate the dynamics of blood lactate, pH and base
      excess (BE) as a tool for assessing the severity of fetal hypoxia and predicting
      neonatal outcome. METHODS: 79 neonates (> or = 34 gestational weeks) were
      included and followed up until discharge: 43 with pathologic fetal hearth rate
      patterns and/or 1-minute Apgar score < 7 ("asphyxia group"); 36 without obstetric
      or clinical signs of asphyxia (control group). Samples from umbilical artery
      (u.a.), capillary blood at 2h and 12-24 h after birth were analyzed for blood
      lactate, pH and BE. RESULTS: Lactate value (u.a.) was significantly higher (5.3
      +/- 3.4 mmol/l), pH and BE were lower (7.29 +/- 0.05 and -14.1 +/- 5.9 mmol/l) in
      the "asphyxia group" compared to the control group (2.7 +/- 1.2 mmol/l, 7.29 +/-
      0.05 and -5.9 +/- 3.3 respectively). The 2 h lactate-values increased
      significantly in infants with asphyxia (6,.7 +/- 4.7) compared to the controls
      (3.2 +/- 1.1), the 12-24 h values were reduced in the main group (4.6 +/- 1.5)
      and without changes in the controls (3.2 +/- 0.88). Values of pH and BE at 2 h
      and 12-24 h increased progressively in both groups without significant
      differences between them. Hypoxic-ischemic encephalopathy (HIE) stage II-III was
      observed in infants with u.a. pH < 7.05, BE < -15 if u.a. lactate was high and
      progressively increased in next 2 h. CONCLUSIONS: High u.a. lactate values
      correlate with low pH and BE and is a reliable tool for assessing the severity of
      fetal asphyxia. Increasing lactate concentration after birth is better predictor
      of severe HIE.

PMID- 24283062
TI  - [Amniotic embolism--damocles sword or lifebelt?].
AB  - The author deals with classical and contemporary concepts of amniotic embolism in
      terms of medical and legal aspects associated with this potentially lethal
      condition.

PMID- 24283063
TI  - [Pregnancy and malignant diseases. Part V. Some rare gynecological tumors during
      pregnancy].
AB  - Neoplasia of the vagina, endometrium and fallopian tube have low frequency in
      pregnant women and in the literature have been reported occasionally. Symptoms of
      cancer during pregnancy is often ignored by patients and physicians, leading to
      delayed diagnosis. This publication examines some characteristics of clinical
      course and management of cases of pregnancy combined with such tumors. Early
      diagnosis and treatment are essential for the favorable prognosis of the disease
      as well as of the pregnancy.

PMID- 24283064
TI  - [Anatomy and physiology of autonomic pelvic innervations].
AB  - Autonomic innervation is responsible for the correct function of the organs in
      the pelvis. Retroperitoneal surgery is associated with trauma of the nerve
      structures. For this reason a detailed knowledge of topographic anatomy of the
      pelvis is needed, when surgery for oncological diseases or endometriosis is
      performed. Faster recovery, decrease of the number of postoperative complications
      and a better quality of life are the result of the nerve-sparing approach.

PMID- 24283065
TI  - [Group B streptococci as a cause of neonatal infections in humans: epidemiology,
      pathogenesis, clinical features, treatment and prophylaxis].
AB  - This paper aims to draw the attention of Bulgarian gynecologists, pediatricians,
      microbiologists on group B streptococci as a cause of serious invasive neonatal
      diseases associated with high mortality rate or disability. Epidemiology,
      pathogenesis and clinical features of the infection are described. Data on the
      antibiotic susceptibility and recommendations for treatment are presented. The
      main purpose of the paper is to lay particular stress on the importance of
      intrapartum antibiotic prophylaxis for pregnant women who are positive for
      rectovaginal group B streptococcal colonization. This measure was introduced in
      the USA (guidelines from 1996, 2002, 2010 years), it proved its efficacy and now
      a lot of the European countries put efforts to adopt it in their health-care
      system.

PMID- 24283066
TI  - [Laparoscopy and early ovarian cancer].
AB  - Review of modern opinions and tendencies, concerning the role of laparoscopic
      surgery for the staging and treatment of ovarian cancer stage I-II. CONCLUSION:
      The laparoscopic approach of surgical staging of early ovarian cancer is equal
      and even has more advantages then conventional laparotomy if it is performed from
      gynecologists- oncologists with enough skills and experience in laparoscopic
      surgery.

PMID- 24283067
TI  - [Polycystic ovarian syndrome and obstructive sleep apnea].
AB  - Polycystic ovarian syndrome (PCOS) is one of the most common endocrine
      disturbances in women of reproductive age. Recently it has been postulated that
      its presence is linked to increased risk for cardiovascular diseases and type 2
      diabetes in affected women. This makes necessary that PCOS is accepted not only
      as a reproductive issue, bus as a serious metabolic disease that carries
      important health risks with increasing age. In the contemporary studies much
      attention is given to PCOS comorbidites, including cardiovascular diseases and
      obstructive sleep apnea (OSA). OSA is a chronic condition that is characterized
      by repeating collapsing of upper airways during sleep that leads to severe
      hypoxemia and frequent awakening. OSA is a relatively rare condition in
      premenopausal women without PCOS and is commonly associated with obesity. On the
      other hand it is thought that PCOS patients have significantly higher risk. OSA
      severity is directly linked to plasma glucose and insulin levels and homeostatic
      model assessment (HOMA)-index in PCOS patients. It appears that the progressive
      worsening of PCOS clinical presentation leads to OSA that in turn aggravates the
      metabolic disturbances, associated with the syndrome.

PMID- 24283069
TI  - [Challenges in front of the modern obstetrics and gynecology].

PMID- 24283068
TI  - [Hypotension and hydration during spinal anesthesia for caesarean section].
AB  - Spinal anesthesia is the technique of choice for elective cesarean section. It is
      easily achievable, fast and reliable technique. Maternal hypotension is a
      complication of spinal anesthesia, which is associated with adverse effects on
      both the mother and the fetus. Thus, the aim of the anesthesiologists should be
      to treat maternal hypotension quickly and efficaciously, or better yet, to
      actively prevent it. In current practice the application of vasopressors to
      maintain arteriolar tone is the most widely used strategy for the prevention of
      hypotension induced by spinal anesthesia. Other methods such as left tilt of the
      operating table, decreasing aortocaval compression and hydration are also
      routinely applied. Possible four different methods of intravascular hydration:
      (1) crystalloid preloading, (2) colloid preloading, (3) crystalloid co loading,
      and (4) colloid co loading.

PMID- 24283070
TI  - [The role of insulin resistace in preeclampsia].
AB  - INTRODUCTION: Contemporary data show that there is a link between insulin
      resistance and preeclampsia (PE) due to many common features. MATERIAL AND
      METHODS: We examined 90 pregnant women at the clinic of Obstetrics and Gynecology
      at the University Hospital "St.George". 35 of them were preeclamptic and 55
      normotensive. Glucose levels were measured at 0, 1, 2 h after OGTT (after 75 g.
      oral glucose administration). Insulin levels were also measured and HOMA IR was
      evaluated. RESULTS: Fasting glucose and insulin levels were similar in both
      groups and showed no statistical significance. HOMA IR was higher in the
      preeclamptic group 2.89 vs 2.09 for normotensive group no statistical
      significance was shown. CONCLUSION: Our results indicate that PE is not
      associated with insulin resistance.

PMID- 24283071
TI  - [Tumor size and prognosis for patients with epithelial ovarian carcinoma at early
      stage].
AB  - The goal of the research is to discover and analyze the dependence of survival on
      the tumor size in a cohort of 215 female patients with early epithelial ovarian
      cancer fallowed up for 13 year period (2000-2012). After multiple analyze among
      18 other prognostic factors, using Cox proportional regression, tumor size
      remained one of five most significant. CONCLUSION: The bigger the size of the
      tumor, the poorer the prognosis for the overall survival (p = 0.0001) and
      progression free survival (p = 0.4) of patient with epithelial ovarian cancer at
      early stage.

PMID- 24283072
TI  - [Mini-invasive treatment by cases of moderate and severe pelvic endometriosis].
AB  - OBJECTIVE: The purpose is to investigate the characteristics of the performed
      mini-invasive surgical treatment by patients with III-IV stage of pelvic
      endometriosis and to establish the advantages of this surgical approach, such as
      the concomitant complications. MATERIAL AND METHODS: 90 patients, who underwent
      operation, with histologically proved endometriosis were studied for a period of
      2 years: 60 of them with moderate and 14--with severe endometriosos, determinated
      by the revised ASRM classification. RESULTS AND DISCUSSION: The most commonly
      done laparoscopic operation is the cystectomy--totally 57 (77%) for the whole
      group, followed by the cystadnexectomy--11 cases (14.9%). By 4 of the cases
      (5.5%) there was a conversion into laparotomy and by 2 of the cases (2.7%) mini
      invasive surgical procedures were accomplished. CONCLUSION: Mini-invasive
      approach by patients with pelvic endometriosis offers several options: to stage
      the condition, to diagnose the tubal sterility and to perform surgical treatment.
      In this study we establish the structure of the accomplished operations, noting
      the low count of complications and conversions, such as the short operative time
      and recovery days.

PMID- 24283073
TI  - [Stillbirth rate and perinatal mortality--criteria for quality of prenatal
      obstetric care].
AB  - AIM: To determine the frequency and structure of stillbirth rate, its relative
      share compared to PM, the trends for the period of 2007-2012 and their dependence
      to birth weight of the fetus and newborn. MATERIAL AND METHODS: The birth rate,
      stillbirth rate and PM for the period of 2007-2012 have been followed up
      retrospectively according to data provided by the department of Obstetrics &
      Gynecology in University hospital "St. George" Plovdiv. The trends of those two
      indicators have been established, their relationship to and dependence of fetal
      and newborn birth weight. Representative and correlative analyses have been used.
      RESULTS: During the period being analyzed 13 558 deliveries have been registered.
      13.4 per thousand (183) of them are stillbirths, and 92.3% (169) died antenatal.
      After 2010 the birth rate decreases. Stillbirth rate increases from 13 per
      thousand in 2009 to 20.6 per thousand in 2012. It is mostly due to prematurity,
      which for the past two years are mostly with extremely low birth weight (57.2%).
      Antenatal stillbirth rate prevails. Intranatal fetal death is being observed
      significantly less, but in those cases where it is, the premature with weight 600
      999 grams play a major role. Increased stillbirth rate maintains a high PM and
      constitute more than 2/3 of it. CONCLUSIONS: Against the backdrop of lower birth
      rate, the stillbirth rate and PM remain high. In the last 2 years they are
      presented mainly by premature weighing 600-999 grams. The prevalence of antenatal
      stillbirth rate means good control of delivery but refers to the prenatal period,
      which is related to the quality of the obstetric care.

PMID- 24283074
TI  - [Respirtory distress in newborns of mothers with factor V-Leiden thrombophilia].
AB  - AIM: The main aim of the trial is to determine the frequency of respiratory
      distress syndrome / RDS/ and disorders of coagulation in infants of mothers with
      thrombophilia. MATERIALS AND METHODS: In 51 newborns of mothers with
      thrombophilia were evaluated the presence of respiratory distress and maternal
      fetal infection /MFI/. The children were divided in two groups: Group I--16
      newborns of mothers with thrombophilia and Group II--15 healthy children. We
      analyzed Hb, Ht, Er, Thr, prothrombin index /INR/, activated partial
      thromboplastin time /aPTT/ in both groups. RESULTS: The analysis of Hb, Ht, Er,
      Thr showed no evidence of anemia or coagulopathy with platelet consumption. In
      64.7% of children was observed respiratory distress syndrome during the first
      days, 21.5% had severe respiratory distress /RD/, that required intubation and
      assisted ventilation. Only in 10/19.6%/ children with RDS there were data proving
      MFI/high CRP and positive microbiological samples/. There was no significant
      difference in the INR value in Group I/1.5 +/- 0.3/ and group II/1.6 +/- 0.1/.
      The children of mothers with thrombophilia had significantly more shortened
      aPTT/35, 1s +/- 4.2/ compared with the control group: aPTT/43.9 +/- 4,4/.
      CONCLUSION: The high incidence of RDS and shortened aPTT indicate that maternal
      thrombophilia is a risk factor for thrombosis in newborns. MFI that are
      accompanied with activated PAI also lead to thrombosis, especially in children in
      Neonatal Intensive Care Units. These results point out that there should be
      prevention of other risk factors for thrombosis such as dehydration and placement
      of central venous catheters.

PMID- 24283075
TI  - [In vitro maturation--a potential approach of infertility treatment of patients
      with PCOS].
AB  - Polycystic ovary syndrome (PCOS) affects about 15-20% of women of reproductive
      age. This is a heterogeneous condition characterized by a combination of
      menstrual cycle disturbances, hyperandrogenism and polycystic ovaries. A
      significant percent of these women comes to the necessity of assisted
      reproduction procedure. During the conventional procedure of in vitro
      fertilization (IVF) the patients are being exposed to a controlled ovarian
      hyperstimulation (COH) with gonadothropine hormones with the purpose of ensuring
      collection of numerous mature oocytes for fertilization and respectively
      obtaining numerous embryos for selection and embryotransfer. The
      supraphysiological doses of exogenous gonadothropines used for COH often lead to
      an excessive ovarian response, characterized by the development of numerous
      follicles of different size and different quality, aspiration of immature oocytes
      and higher risk of severe ovarian hyperstimulation syndrome (OHSS) in women with
      PCOS. The retrieval of immature oocytes from unstimulated ovaries followed by in
      vitro maturation (IVM) procedure appears a potential therapy which eliminates
      aforenamed risks and respectively is highly beneficial for application to women
      with PCOS.

PMID- 24283076
TI  - [Potential bioeffects in interaction between ultrasound and tissue--safety of
      diagnostic ultrasound].
AB  - Diagnostic ultrasound has an incredible impact in medicine, especially in
      obstetrics and gynecology practice. Due to wide clinical practice the knowledge
      about potential bioeffects in tissues are mandatory. Safety assurance for
      diagnostic ultrasound in obstetrics is interesting topic, there is a lack of
      proven harmful effects in fetuses. Technical developments in imaging suggest
      higher energy exposition levels. For this reason education and responsibility
      play important role in safety use of the ultrasound.

PMID- 24283077
TI  - [A case of bilateral tubal pregnancy after IVF - ET].
AB  - The authors describe a rare case of bilateral tubal pregnancy after IVF. The
      patient is with secondary infertility. The preceding diagnostic laparoscopy
      excluded the presence of tubal factor. The results of the spermogram show average
      to severe form of Oligoasthenozoospermia. Short protocol with GnRH-antagonist was
      performed and two embryos were transferred on the third day. On the 36th day
      after the embryo transfer the patient was hospitalized with abdominal pain in the
      right hypogastric region, clinical and ultrasound indications for hemoperitoneum.
      Urgent laparotomy was performed followed by salpingectomy dextra due to
      hemoperitoneum caused by tubal abortion. The examination of the left adnexa
      reveals uruptured tubal pregnancy in the isthmic part of the tube and the
      decision for salpingectomy sinistra was taken. Histological examinations
      confirmed the diagnosis of ectopic pregnancy in both tubes. The frequency of some
      rare forms and localizations of ectopic as well as heterotopic pregnancies
      increase after ART.

PMID- 24283078
TI  - [Ovarian vein syndrome during pregnancy--diagnostic and treatment].
AB  - PURPOSE: To access the presence of Ovarian Vein Syndrome in second trimester
      pregnancy and safety and effectiveness of stents insertion in symptomatic
      hydronephrosis during pregnancy. MATERIAL AND METHODS: From 01.01.2007 to
      30.12.2011, 66 women were hospitalized in the Urology Clinic at the University
      Hospital "St. George" Plovdiv. Sixty six patients presented acute pyelonephritis
      and painful hydronephrosis. 61 cases were with right hydronephrosis (92%), 2 (3%)
      on the left side and 3 (5%) with hydronephrosis in both sides. On the Ultrasound
      Doppler investigation, 61 cases with right hydronephrosis were with varicose
      right ovarian vein anomalies, which cause unilateral ureteral obstructions. Using
      ultrasound guidance, 66 retrograde ureteral stents were successfully placed under
      local anesthesia. RESULTS: In 66 patients with urinary infection, we observed
      remission of fever during the first 24-48 hours after the placement of the
      ureteral stents. CONCLUSIONS: Ovarian vein syndrome is a ureteral dilatation
      secondary to ovarian vein dilatation. The majority of cases are diagnosed during
      pregnancy, with a 90% predominance on the right side. Retrograde ureteral
      stenting is an effective, simple and safe method in treating symptomatic
      hydronephrosis during pregnancy.

PMID- 24283079
TI  - [Anormalies of the fetal posterior fossa during second trimester--diagnosis and
      management].
AB  - Six cases of Dandy-Walker malformation are presented. Five of them, diagnosed in
      18-20 gestation weeks, respectively ended up in intermission of the pregnancy in
      second trimester and one case, diagnosed in 29-30 gestation weeks ended up in
      giving birth to a hypotrophical foetus in a good general state. The opportunities
      for diagnosis by 2D/3D echography have been considered in accordance with the new
      classification of abnormality of the fetal posterior fossa fluid collections.
      This is a clinical approach and a possible way out for the pregnancy and the new
      born baby.

PMID- 24283080
TI  - [Cervical intraepithelial neoplasia: an attempt to propose rules for good medical
      practice].
AB  - The authors emphasize the advantages of the term "cervical intraepithelial
      neoplasia" (CIN) over "dysplasia" and "carcinoma-in-situ". The rules for good
      medical practice in treating CIN are based on several starting points, namely:
      proven role of the human papillomavirus (HPV) in the development of CIN; current
      possibilities to diagnose and to prevent HPV infections; morphological stigmata
      of CIN within the epithelium; possibilities to treat CIN and lack of
      possibilities to treat HPV infection; assessment of the patient 's reproductive
      potential. In recent cases of CIN1 the history of anti-HPV vaccination is an
      important factor in choosing the best treatment protocol. In cases of persistent
      CIN1 treatment protocols are influenced by the presence/absence of high-risk
      types of HPV. In recent cases of CIN2 treatment protocols vary according to the
      extent of the lesion, as well as its penetration within the cervical canal. The
      latter sign is of foremost importance in recent cases of CIN3. Treatment
      protocols for all the above mentioned conditions, for persistent CIN2 and CIN3,as
      well as for post-treatment recurrences are presented in flow chart form.
      Patients' age and reproductive potential should be taken into consideration in
      selected cases of CIN2+. CIN in pregnant patients deserves a more conservative
      approach.

PMID- 24283081
TI  - Doctors and exercise.

PMID- 24283082
TI  - Non-immune hydrops fetalis.
AB  - BACKGROUND: Non-immune hydrops fetalis (NIHF) is a rare fetal condition with a
      very high mortality in spite of advances in prenatal diagnostic techniques, early
      detection, and individualized management. Despite advancement in fetal therapy
      and rapidly developing new knowledge about the aetiology and prenatal diagnosis,
      its management has remained controversial. METHODS: This is a descriptive review
      ofNIHF. RESULTS: NIHF is a rare fetal condition that presents in an extremely
      acute manner with almost 90% mortality. Fetal cardiac anomalies are the most
      common cause and chromosome anomalies are the second-most-common cause. The worst
      prognosis was related to prematurity, severe hydrops, anaemia, cardiac
      malformations, chromosomal disorders and congenital infections. Fetal
      interventions includeboth medical and surgical modalities. CONCLUSION: NIHF is a
      rare condition with high prenatal mortality. The exact pathophysiology is still
      poorly understood. It is important to detect NIHF early, diagnose the underlying
      cause and institute appropriate treatment. There is need for autopsy of all
      fetuses or neonates who die from NIHF.

PMID- 24283083
TI  - Neonatal head injury unrelated to birth trauma in South-East Nigeria.
AB  - BACKGROUND: Neonatal head trauma resulting from causes other than birth trauma
      has rarely been the focus of many a research theme in the literature.
      AIM/OBJECTIVE: To highlight the occurrence of non-birth trauma related neonatal
      head injury, and evaluate the causes and outcome of treatment. METHODS: A 3 year
      retrospective review of neonatal patients with head injury from two tertiary
      hospitals in South-East Nigeria between July 2009 and June 2012 (n-37). Data was
      collected from patients' birth and medical records. Data was analyzed using the
      SPSS version 15. RESULT: Among the one hundred and seventy-six cases (11.78)%
      pediatric head injury cases seen, thirty seven (2.48)% occurred in neonatal
      patients. The most common cause of head injury was fall 22 cases [59.5%].
      Children of mothers with low educational qualification were more likely to
      sustain falls 22 cases (59.5%). Road traffic accident (n = 15) was associated
      with more severe injuries and poorer outcome. Operative treatment was associated
      with increased mortality (two of three cases). The mortality rate in our series
      is 8.10%. CONCLUSION: Reduction of neonatal head trauma could be achieved through
      improved maternal education.

PMID- 24283084
TI  - Comparative effects of single shot low dose spinal bupivacaine only and
      bupivacaine with fentanyl on labour outcome.
AB  - BACKGROUND: Childbirth has been recognised as the most painful experience known
      to women. This study aimed at studying the efficacy and safety of the single shot
      spinal analgesia for pain relief in labour. MATERIALS AND METHODS: One hundred
      and twelve parturients in labour were randomized into two groups of 55 paturients
      each. Group B received 2.5 mg of spinal plain bupivacaine only while Group BF had
      2.5 mg plain bupivacaine with 25 gg of fentanyl. Onset of sensory block, time to
      achieve maximum sensory block, duration of sensory and motor block and the level
      of block were recorded. The need for oxytocin augmentation, instrumental
      delivery, neonatal Apgar scores and umbilical artery blood pH were recorded.
      RESULTS: The numeric rating pain scores for groups B and BF were significantly
      reduced from a mean prespinal score of 8.17 +/- 0.96 cm and 8.30 +/- 0.23 cm
      respectively to a mean post-spinal pain score of 0.23 +/- 0.45 cm and 0.09 +/-
      0.47 cm respectively, p = 0.000. The mean duration of analgesia in Group B was
      61.60 +/- 6.47 mins while it was 128.98 +/- 21.61 mins in Group BF, p = 0.000.
      CONCLUSION: The study showed that low dose spinal bupivacaine either alone or in
      combination with fentanyl is safe for labour analgesia, but the combination f
      bupivacaine with fentanyl provided much more prolonged pain relief

PMID- 24283085
TI  - Cardiovascular risk factors in middle-aged and elderly residents in South-East
      Nigeria: the influence of urbanization.
AB  - Cardiovascular diseases (CVD) were previously considered a problem of the
      developed nations only. Emerging facts show that CVD and their risk factors are
      now prevalent in developing countries. We carried out a cross-sectional,
      population-based survey to determine the relation between place residence (rural
      or urban) and the burden of CVD risk factors in South East Nigeria.
      Hypercholesterolaemia, hypertension, abnormal blood glucose and obesity were
      assessed for, in middle-aged and elderly residents of two communities in Enugu,
      South East Nigeria. A total of 543 adults (308 at Ogwofia Owa and 235 at Emene)
      participated in the study. The mean and 95% CI for mean of the characteristics of
      subjects showed that they were in the middle-age group with apparently normal
      mean cardiovascular risk indices except for systolic and diastolic blood pressure
      indices which suggested pre-hypertension. The subjects residing in the rural area
      were older than those residing in the urban area but cardiovascular risk factors
      had higher mean values in urban residents except systolic blood pressure (SBP).
      The most prevalent cardiovascular risk factors in the study group were
      hypertension and obesity. Urban residence was found to influence the prevalence
      of risk factors, specifically obesity and diastolic hypertension.

PMID- 24283086
TI  - Regular screening among sportsmen in Nigeria: rationale and basis.
AB  - BACKGROUND: Participation in regular prolonged physical exercise is associated
      with specific adaptation in cardiac structure and function which could predispose
      to sudden cardiac death and has been recorded in celebrated cases and with an
      increasing frequency in recent time especially in Nigerian footballers. There is
      no policy or strategy in place for preventing recurrence OBJECTIVE: To review the
      current literature on sudden death in athletes generally, identify current
      strategies that have been found useful and recommend measures to prevent or
      reduce prevalence in Nigerian sportsmen. METHOD: Internet search on the subject
      using Google and Medline web search engine. The search words were sudden death,
      athletes, Africans and sports screening. RESULT: Sudden death in young athletes
      is rare occurring in in n 100,000 to 1 in 280,000 persons per year and
      hypertrophic cardiomyopathy is the commonest cause and blacks are more affected
      than caucasians. Screening guidelines are available in some countries and
      mandatory pre participatory screening has reduced the incidence of sudden death
      in athletes in these countries. In Nigeria there is no legislation or policy on
      routine screening in sportsmen or measures to prevent or reduce incident of
      sudden death in athletes. CONCLUSION: There has been increased report of sudden
      death in Nigerian footballers in recent years and the investigations into these
      deaths are shrouded in secrecy. There is no policy for routine screening of
      sports participants in Nigeria, there is urgent need to develop a policy to
      ensure appropriate pre participation screening for all sportsmen and women each
      year or at the beginning of each sports season.

PMID- 24283087
TI  - Oesophageal atresia and tracheooesophageal fistula: a 12 years experience in a
      developing nation.
AB  - OBJECTIVE: To document our 12 years experience in the management of oesophageal
      atresia and tracheooesophageal fistula. METHOD: The study was carried out at the
      University of Nigeria Teaching Hospital (UNTH) Enugu Nigeria between January 1997
      and December 2008. The paediatric ward and theatre records of patients with
      oesophageal atresia and trachea oesophageal fistula were reviewed. The data
      extracted include: age at presentation, age at referral, reasons for delay
      referral (> 24 hrs from birth). Associated anomalies, Time interval from
      diagnosis to intervention, Operative procedure, and outcome. RESULT: Ten patients
      were studied, eight males and two females, ratio 4:1. They were all referred from
      outside the study centre. The average age at presentation was 5.3 days with a
      range of 2-12 days. The mean age at referral was 3.9 days. Two patients died
      before surgical intervention. The remaining eight that had surgery done, only one
      was discharged alive to surgical out patient but was lost to follow up.
      CONCLUSION: Delay in arriving at a diagnosis, late referral, associated
      congenital anomalies and comorbidities contributed to the poor out come. High
      index of suspicion, early diagnosis and referral, improved facilities and
      experience of the attending team will make for a favourable out come.

PMID- 24283088
TI  - Visual defects and commercial motorcycle accidents in south eastern Nigeria.
AB  - BACKGROUND: Commercial motorcyclists are a regular part of our highways,
      especially with the decrease in the number and quality of good roads. This study
      is aimed at determining the role of vision if any in the increasing number of
      road traffic accidents (RTA's) among commercial motorcyclists in Enugu
      metropolis, Nigeria. METHOD: A cross sectional survey with a multi stage random
      sampling design was used to select the 615 commercial motorcyclists in Enugu
      metropolis enrolled in the study. RESULT: Out of the 615 motorcyclists, seven
      (1.14% +/- 0.70%) motorcyclists had visual impairment (< 6/18-3/60). Visual field
      defect was noted in 2.3% +/- 0.98% while 2.6% +/- 0.98% had colour vision defect.
      The prevalence of road traffic accident (RTA) was 57.7%. Visual impairment was
      not significantly associated with RTA (P = 0.333) while visual field defect (P =
      0.000), and colour vision defect (P = 0.003) were positively associated with RTA.
      Inexperienced riders had significantly more RTAs than their counterparts (P =
      0.000). CONCLUSION; Visual field defect, and colour vision defect were
      significantly associated with RTA but this finding is in the backdrop of poor
      training, and inexperience which also significantly affected RTA among the
      predominantly young riders involved in RTA.

PMID- 24283089
TI  - Uterine rupture: trends and feto-maternal outcome in a Nigerian teaching
      hospital.
AB  - OBJECTIVE: To determine the trends, predisposing factors, maternal and fetal
      outcome of cases of uterine rupture managed at the University of Abuja Teaching
      Hospital. METHOD: A retrospective review of all cases of ruptured uterus managed
      at the University of Abuja teaching hospital, Gwagwalada, between January 2006
      and December 2010 was conducted. RESULT: There were 9604 deliveries in the
      hospital during the period of review out of which 82 were cases ruptured uterus,
      giving an overall incidence of 0.85% or 1 in 117 deliveries. They were mainly
      women of low parity with a mean age of 31.8 years. The commonest predisposing
      factor was injudicious use of oxytocin occurring in 38.7% of cases and was
      followed closely by previous caesarean section scar (28.0%). Prolonged obstructed
      labour was the third commonest cause of uterine rupture (18.7%) and occurred only
      in the unbooked patients. There were 11 maternal deaths which gave a maternal
      case fatality rate of 14.7%. All the deaths occurred in women who had intrapartum
      care in places other than the teaching hospital. There were 68 perinatal deaths
      which gave a fetal case fatality rate of 90.7% and all the babies that survived
      were in patients that had intrapartum care in the teaching hospital. CONCLUSION:
      Ruptured uterus is a common obstetric emergency in Nigeria's Federal Capital
      territory and is associated with high maternal and perinatal morbidity and
      mortality. It is however preventable when the quality of antenatal care,
      intrapartum care and medical facilities are improved.

PMID- 24283090
TI  - Knowledge and utilization of computer-software for statistics among Nigerian
      dentists.
AB  - BACKGROUND: The use of computer soft ware for generation of statistic analysis
      has transformed health information and data to simplest form in the areas of
      access, storage, retrieval and analysis in the field of research. This survey
      therefore was carried out to assess the level of knowledge and utilization of
      computer software for statistical analysis among dental researchers in eastern
      Nigeria. METHOD: Questionnaires on the use of computer software for statistical
      analysis were randomly distributed to 65 practicing dental surgeons of above 5
      years experience in the tertiary academic hospitals in eastern Nigeria. The focus
      was on: years of clinical experience; research work experience; knowledge and
      application of computer generated software for data processing and stastistical
      analysis. RESULT: Sixty-two (62/65; 95.4%) of these questionnaires were returned
      anonymously, which were used in our data analysis. Twenty-nine (29/62; 46.8%)
      respondents fall within those with 5-10 years of clinical experience out of which
      none has completed the specialist training programme. Practitioners with above 10
      years clinical experiences were 33 (33/62; 53.2%) out of which 15 (15/33; 45.5%)
      are specialists representing 24.2% (15/62) of the total number of respondents.
      All the 15 specialists are actively involved in research activities and only five
      (5/15; 33.3%) can utilize software statistical analysis unaided. CONCLUSION: This
      study has i dentified poor utilization of computer software for statistic
      analysis among dental researchers in eastern Nigeria. This is strongly associated
      with lack of exposure on the use of these software early enough especially during
      the undergraduate training. This call for introduction of computer training
      programme in dental curriculum to enable practitioners develops the attitude of
      using computer software for their research.

PMID- 24283092
TI  - Giant inguino-scrotal hernias seen at the University of Port Harcourt Teaching
      Hospital.
AB  - BACKGROUND: Inguino-scrotal hernias are a common surgical problem especially in
      our rural areas. The aim of this study is to review six patients seen with giant
      inguinoscrotal hernias at the University of Port Harcourt Teaching Hospital.
      METHODS: A retrospective review of patients seen between 1985 and 1995 at the
      University of Port Harcourt Teaching Hospital with giant inguino-scrotal hernias
      was carried out. RESULTS: The duration of the hernias ranged from twelve to
      thirty years. All the patients were above fifty-five years of age and eighty
      percent of them worked as farmers. Ninety percent of the patients developed
      cardio-respiratory difficulties when reduction was attempted during the
      operation. One patient had his operation converted to a bowel resection in order
      to allow for easy reduction. All developed severe scrotal haematoma and sepsis,
      one a full blown scrotal gangrene and another faecal fistula that resulted in
      death. CONCLUSION: In view of the intensive care required following surgery and
      the complications of surgery, we are advocating a policy of wait and see till
      features of intestinal obstruction present for surgery to be contemplated.

PMID- 24283091
TI  - Prevalence, presentation and management of polycystic ovary syndrome in Enugu,
      south east Nigeria.
AB  - BACKGROUND: Polycystic ovary syndrome is the most common gynaecological endocrine
      disorder in women of reproductive age yet, its prevalence and management has not
      been documented in our area. OBJECTIVE: To determine the prevalence, presentation
      and management of polycystic ovary syndrome among women in Enugu, south east
      Nigerian. METHOD: A prospective descriptive study of women with polycystic
      ovaries seen in two major Infertility Clinics in Enugu, South East Nigeria over a
      2 year period. RESULT: A total of 342 women presented with infertility in the
      centres within the two year period, out of whom 62 had PCOS. PCOS occurred in
      18.1% of women in the infertility clinics of the two institutions. The common
      modes of presentation were: inability to conceive (infertility) in 52 (83.9%),
      oligomenorrhoea in 45 (72.6%), obesity in 32 (51.6%), LH/FSH ratio > 2 in 28
      (45.2%), hyperprolactinaemia in 26 (41.9%) and hirsuitism in 19 (30.6%) women.
      Ovulation induction was carried out in 42 of the 50 women with anovulatory
      infertility only. For those 42 women, the mean number of induced cycles was 2.6 =
      1.7 (range: 1-6) with 33 (78.6%) of the women being able to do only 3 induced
      cycles or less. The ovulation induction agents used were clomiphene citrate and
      human menopausal gonadotrophin either singly or in combination with tamoxifen or
      bromocryptine. Adjunctive treatments offered consisted of weight reduction in 20
      (40.0%) women, metformin in 11 (22.0%) women and dexamethasone in 10 (20.0%)
      women. CONCLUSION: PCOS is fairly common occurring in approximately one in six
      infertile Nigerian women. Infertility, oligomenorrhoea, obesity, LH/FSH ratio >
      2, hyperprolactinaemia and hirsutism are the commonest presenting features. On
      individualized management, about two-fifths of them conceive either spontaneously
      or following ovulation induction, despite poor compliance to recommended drug
      regimen.

PMID- 24283093
TI  - An audit of diagnosis and treatment of sepsis in north-central Nigeria.
AB  - BACKGROUND: We audited the diagnosis and antibiotic therapy of patients admitted
      with sepsis in a resource-limited Nigerian hospital setting in order to improve
      the quality of sepsis care. METHOD: We conducted a retrospective analysis of the
      records of medical patients admitted for sepsis at the Jos University Teaching
      Hospital between September 2011 and August 2012. Data analysis included age, sex,
      appropriateness of sepsis diagnosis/severity, comorbidities, utility/yield of
      sample cultures, antibiotic therapy, duration of hospital stay and treatment
      outcome. RESULT: Only 94 out of 142 cases (66.2%) were judged to meet the
      diagnostic criteria for sepsis. Out of the 94 patients, 77 (82%) were
      appropriately classified for sepsis severity. Nineteen patients (20%) met
      criteria for severe sepsis/septic shock. The commonest comorbidity was HIV/AIDS
      (57.3%). All the patients received empirical antibiotic therapy but in 23 cases
      (24.5%), the empirical prescriptions were judged inappropriate and none was
      administered within one hour of diagnosis. Blood cultures were available to guide
      definitive antibiotic therapy in only 12.5% of cases. The median (range) duration
      of hospital stay was 12 (1-70) days while the in-hospital mortality rate was 53%.
      CONCLUSION: The management of sepsis was suboptimal in our setting and mortality
      was high. We recommend adoption of standard sepsis guidelines to ensure optimal
      management and improved outcome.

PMID- 24283094
TI  - Awareness, ownership and utilization of insecticide treated nets in Abavo
      community of Delta State.
AB  - BACKGROUND: Despite free distribution of insecticide treated nets in Nigeria, the
      use it as a means of malaria prevention and control has not been fuIly embraced.
      AIM: The aim of this survey was to determine the level of awareness, ownership
      and utilization of insecticide treated nets among residents of Abavo community,
      Delta State Nigeria METHOD: It is a descriptive cross-sectional survey conducted
      among 250 heads of households. RESULT: One hundred and seventy five (70%)
      respondents were aware of insecticide treated net as a means of prevention
      against malaria, 111 (44%) claimed to own insecticide treated nets. On further
      inspection of houses of those who claimed to own ITNs, seventy four (66%)
      actually had theirs hanged, the rest were either in their packs or not seen.
      Ninety five (38%) respondents out of the total sleep under insecticide treated
      net. About 92 (70%) households having under-five and 39 (81.3%) of households
      having pregnant women claim to use ITNs. It was observed that the level of
      education (chi2 = 48.35, p = 0.001), presence of under 5 children in a household
      ?2 = 7.229, p = 0.027) influenced ownership of Insecticide treated nets. In
      conclusion despite a high level of awareness about ITN found in this survey,
      ownership and utilization of insecticide treated nets were low.

PMID- 24283095
TI  - A survey of women's knowledge and perception of hormone replacement therapy (hrt)
      in Enugu, South East Nigeria.
AB  - BACKGROUND: As a result of alteration in the physiological, biochemical and
      psychological environment of a woman due to menopause, there may be need for
      hormone replacement therapy (HRT). This concept is new in our poor resource
      setting, thus the knowledge and perception of HRT will be invaluable to
      appropriate adjustment to menopausal period. OBJECTIVE: The objective of this
      study was to determine the knowledge and perception of hormone replacement
      therapy among women in Enugu South-East Nigeria. METHOD: This was a cross
      sectional survey of gynaecology clinic attendees at the university of Nigeria
      Teaching Hospital (UNTH), Enugu. These women were randomly selected. Data were
      analyzed using SPSS software. The primary method used was cross tabulation.
      RESULT: The knowledge and perception of HR among women of South East Nigeria is
      poor and related to the level of education. One hundred and sixty eight women
      (38.9%) had knowledge of HRT and only 48 (11.1%) had taken it in the past.
      Currently none was using HRT despite experiencing menopausal symptoms. Majority
      of women were ignorant of HRT and took climacteric symptoms as part of aging
      process. CONCLUSION: The knowledge and perception of HRT is poor and limited.
      Public enlightenment would help to improve awareness of climacteric symptoms.
      Women at high risk for menopausal diseases should be advised on HRT.

PMID- 24283096
TI  - Pattern and predictors of partner disclosure of HIV status among HIV positive
      pregnant women in Nnewi Nigeria.
AB  - BACKGROUND: Sub-Saharan Africa has continued to bear the greatest burden of
      HIV/AIDS epidemic in the world. Partner disclosure of status may create
      opportunities for support or rejection. OBJECTIVE: This study evaluated the
      pattern of partner disclosure of HIV positive women, their partners' reaction and
      factors that affect disclosure of HIV status to partners. METHODOLOGY: This was a
      descriptive cross-sectional study conducted among pregnant women in Nnamdi
      Azikiwe University Teaching Hospital Nnewi An interviewer-administered
      questionnaire was used to obtain relevant information from the subjects. Data was
      analysed using SPSS version 20 software. RESULTS: One hundred and twenty six
      women participated in this study. The mean age of the women was 30.4 years +/- 5
      while the mean parity was 2.6 +/- 1. All the patients had at least primary
      education with 63.5% having secondary education as the highest educational
      attainment. One hundred and sixteen (92.1%) were in monogamous marriage. One
      hundred and fourteen 90.5%) had disclosed their HIV status to their partners.
      Eighty-three (66.7%) of the women did this by self. Partners initial reaction was
      supportive in 84 (66.7%) of the women. Partner's subsequent reaction showed that
      103 (81.2%) were supportive, 7 (5.6%) were indifferent while 4 (3.2%) were
      abusive and violent. The partner's HIV status showed that 54 (42.9) tested
      positive to HIV antibodies while 52 (41.3%) tested negative to HIV antibodies and
      20 (15.9%) do not know partner's HIV status. There was strong correlation between
      disclosure of HIV status with monogamous marriage and duration of illness.
      CONCLUSION: The partners' reaction to HIV status of their female partners was
      largely supportive. Disclosure of HIV status should be encouraged in view of the
      needed support of the partner in management of these women.

PMID- 24283097
TI  - Perception of infertility and acceptability of assisted reproduction technology
      in northern Nigeria.
AB  - BACKGROUND: Infertility is a stigmatized reproductive morbidity with severe
      psycho-social consequences, especially in developing countries. There has been
      little exploration of the public view of infertility and acceptance of assisted
      reproduction in these countries, including Nigeria. OBJECTIVE: To determine the
      public perception of infertility, its causes and factors associated with
      acceptability of Assisted Reproductive Technologies (ART) in Kano, Northern
      Nigeria. METHOD: Using interviewer administered questionnaires, a cross-section
      of 600 adults were interviewed about perceived definition, causes and acceptance
      of ART. RESULT: Majority of the respondents (n = 577, 99.3%) perceived
      infertility as a disease. Only 18.1% (n = 105) of the respondents would consider
      a couple infertile after one year of marriage. Causes of infertility mentioned by
      participants included paranormal events (n = 535, 92.1%), suprapubic pain (n =
      321, 55.2%), induced abortion (n = 187, 32.2%) and sexually transmitted
      infections (n = 177, 30.5%). A minority of respondents (n = 161,27.7%) of
      participants mentioned blocked tubes and 24.6% (n = 143) irregular menstrual
      cycles. Although 36.1% of respondents were aware of ART; only 7.6% were willing
      to accept it. Being male [adjusted odds ratio (AOR) (95% CI)] 2.1 (1.55.72),
      childless [AOR (95% CI)] 2.2 (1.35.95), highly educated [AOR (95% CI)] 3.2
      (1.326.72) and non-Muslim [AOR (95% CI)] 2.3 (1.23.76) were significant
      predictors of acceptance ofART. CONCLUSION: Infertility was correctly perceived
      as a disease, but there were misconceptions about its causes. The low acceptance
      of ART was influenced by socio-demographic factors. There is a need for sustained
      targeted information, education and communication regarding new reproductive
      technologies for fertility management.

PMID- 24283098
TI  - Endoscopic retrograde JJ-stenting of the ureter without fluoroscopy guidance--an
      appraisal of outcome.
AB  - BACKGROUND: JJ- ureteral stenting is a means of relieving ureteric obstruction.
      It is done as a retrograde or antegrade procedure, usually under fluoroscopy
      guidance. We reviewed our results in 2 independent tertiary health centers in
      Nigeria which lack fluoroscopy units. METHODS: A 2 year retrospective review of
      data of patients who had retrograde JJ- ureteric stenting was done. Data relating
      to age, indication and outcome of procedure were retrieved and analysed. RESULTS:
      22 (71%) patients had successful retrograde JJ- ureteric stenting out of 31
      patients who were taken for the procedure. These 22 patients had stenting of 27
      ureteric units. Mean age was 48.5 years. Commonest indication was carcinoma of
      the cervix (31.8%). Commonest complication was irritative lower urinary tract
      symptoms (43.5%). CONCLUSION: In spite of inherent complications, JJ-stenting is
      a simple and safe technique. Therefore, the decision to attempt JJ -stenting in
      carefully selected patients in the absence of fluoroscopy is acceptable.

PMID- 24283099
TI  - Seizure disorder among chronic kidney disease patients in Enugu, South East
      Nigeria.
AB  - BACKGROUND: Seizures are the commonest neurological condition presenting in
      Africa. The pattern of non- epileptic seizures in systemic diseases including
      chronic kidney disease is unknown in South East Nigeria. OBJECTIVES: This study
      examined the pattern of seizures in chronic kidney disease patients in Enugu,
      South East Nigeria. METHODS: This was a retrospective study of chronic kidney
      disease patients who presented to the University of Nigeria Teaching Hospital
      Enugu (UNTH) from January 2007 December 2008. Data from subjects who satisfied
      the inclusion criteria were reviewed and analysed using Statistical Package for
      the Social Sciences version 13.5. Ethical clearance was obtained from the UNTH
      Ethics Committee. RESULTS: There were 145 patients, 95 males and 50 females. Mean
      age was 35 years. Only 5 patients (3,4%) had seizures (mostly generalized tonic
      clonic) associated with severe hypertension. None had hypocalcaemia. Three
      patients (60%) received dialysis with benefit while 2 patients (40%) died before
      dialysis could be done. CONCLUSION: Seizures are infrequent in chronic kidney
      disease patients in Enugu; are commoner in males and those with severe disease.
      Dialysis improved survival in those with seizures. Larger multicentre studies are
      needed to further elucidate the spectrum of Nigeria.

PMID- 24283100
TI  - Esophagitis dissecans superficialis presenting with massive haematemesis in a
      patient with bullous pemphigoid.
AB  - The stratified squamous epithelial lining of the esophagus is similar to that of
      the skin, and occasionally conditions that affect the skin tend to have
      esophageal manifestations. Autoimmune dermatological conditions that present with
      blisters are referred to as bullous dermatoses and have been found to rarely
      present with esophageal involvement. Esophageal epithelium is thought to be
      involved in rare occasions because of its identical epithelial lining to the skin
      and tends to be more frequent among patients with pemphigus vulgaris than in
      those with pemphigoid. Common symptoms from esophageal involvement in bullous
      dermatoses may include heartburn, odynophagia or dysphagia. Rarely, it may
      present with vomiting of sloughed cast of esophageal mucosa or haematemesis. We
      present S A, a 47 year old female who was on outpatient treatment in 2010 at King
      Fahad Medical City for bullous pemphigoid but developed progressive odynophagia
      with massive haematemesis. She was admitted and resuscitated, and endoscopy
      revealed sloughing of esophageal mucosa and bleeding in keeping with esophagitis
      dissecans superficialis. Although association of esophageal dissecans
      superficialis with pemphigus vulgaris has been sparsely reported; to our
      knowledge its association with bullous pemphigoid as in our case has been rarely
      reported in English medical literature.

PMID- 24283101
TI  - Necrobiosis lipoidica diabeticorum: necrobiosis lipoidica diabeticorum in a
      Nigerian from the north. A case report.
AB  - BACKGROUND: Necrobiosis lipoidica is a rare complication of diabetes mellitus.It
      is said to occur more often in people with diabetes,a family history of
      diabetes,tendency to develop diabetes mellitus and those with insulin dependent
      diabetes. METHOD: We report an evaluated case of necrobiosis lipoidica
      diabeticorum residing in the northern part of Nigeria. RESULT: The patient was
      treated for 3 weeks in the hospital on admission and was followed up in the
      general-out-patient department (GOPD) and has been in good health. AIM AND
      OBJECTIVE: To bring to the fore of clinicians this dermal complication of
      diabetes mellitus, the different medical treatments available and the medical
      treatment employed in our index patient. CONCLUSION: That necrobiosis lipoidica
      diabeticorum does exist in our environment and requires a high index of suspicion
      and scrupplelousness in making the diagnosis and treating the patient.

PMID- 24283102
TI  - Angiosarcoma of the cervix: a case and literature review.
AB  - BACKGROUND: Generally, sarcomas of the female genital tract are rare and
      angiosarcomas are extremely rare. They usually have poor prognosis and pose
      serious diagnostic challenges requiring special techniques namely special stains
      and immunohistochemistry for proper elucidation. METHOD: A case report of a 65
      old para 8 (4 alive) widow, 17 years postmenopusal, who presented with history of
      foul smelling brownish vaginal discharge, progressive weight loss and cervical
      lesion. She had examination under anaesthesia and biopsy. RESULT:
      Histopathological result showed features in keeping with angiosarcoma of the
      uterine cervix. CONCLUSION: Although angiosarcoma of the cervix is very rare, it
      is occasionally seen in black women in Nigeria.

PMID- 24283103
TI  - Under-reporting of gossipiboma in a third-world country. A sociocultural view.
AB  - The paper looks at the reason for the low incidence of retained abdominal packs
      following an abdominal operation in a third world country like Nigeria. It is
      generally agreed that this unfortunate situation is underreported. The reason for
      under-reporting is now given a socio-cultural perspective. Fear of litigation as
      would hold in the western world does not seem to be paramount here. Other
      explanations like fear of being made a scapegoat for something which may be due
      to spiritual attacks may be paramount. The paper concludes by recommending that
      the removal of impediments to disclosure of this adverse surgical event will lie
      in education, discouragement of scapegoatism and improvement in hospital services
      in the third world.

PMID- 24283104
TI  - In-training continuing professional development in Nigeria.
AB  - BACKGROUND: Residency programs are geared towards in-depth training in a
      particular specialty. Several academic programs are carried out to achieve this
      and a prerequisite in some departments for accreditation for training of
      residents. METHOD: Review of literature on various residency training continuous
      medical education on clinical meeting also known as grand rounds in some
      hospitals/departments, anaesthetic risk assessment, journal club and case
      reviews. CONCLUSION: New findings are always made in medicine and thus the need
      for updates.

PMID- 24283105
TI  - Impact of negative lesion characteristics of chronic total occlusions on
      procedural outcome and strategy.
AB  - OBJECTIVE: In the past, certain lesion characteristics of chronic total
      occlusions (CTOs) have been shown to have an influence on guidewire crossing and
      thus percutaneous coronary interventional outcome. However, a clear description
      of the individual impact of these characteristics on procedural outcome,
      procedural characteristics and treatment strategy is lacking. The purpose of this
      study was to give a "weight"to these individual characteristics and evaluate
      their influence on interventional strategy. METHODS: Between November 2011 and
      May 2013, a non-randomized, prospective study was conducted in the hospitals of
      Genk and Aalst, leading to the inclusion of 132 consecutive patients. Lesions
      were classified according to the J-CTO (Multicenter CTO Registry of Japan) score
      (Morino et al., 2011). Both antegrade and retrograde procedures were performed.
      For antegrade procedures, a step-up strategy was applied. Univariate and
      multivariate analyses were performed and compared with the results of Morino et
      al.The study end point was general procedural success, defined as successful
      stenting with thrombosis in myocardial infarction 3 flow. RESULTS: Overall
      procedural success was achieved in 74% and according to J-CTO criteria, in 92%
      (easy), 82% (intermediate), 77% (difficult) and 40% (very difficult),
      respectively. Independent predictors included bending, blunt stump, multivessel
      PCI and a retrograde approach with corresponding odds ratios for failure of 5.3,
      2.7, 2.8 and 4.0, respectively. CONCLUSION: Lesion characteristics of CTOs remain
      important in the prediction of success. In this study, bending and a blunt stump
      at the entry site came forth as the most important independent predictors of
      failure.

PMID- 24283106
TI  - The relationship between endothelial nitric oxide synthase 4a/4b gene
      polymorphism and premature coronary artery disease.
AB  - BACKGROUND: Nitric oxide (NO) plays a major role in the regulation of endothelial
      functions and reduced NO synthesis has been implicated in the development of
      coronary atherosclerosis. Endothelial nitric oxide synthase (eNOS) intron 4a/b
      polymorphism has been shown to be related to plasma nitric oxide concentrations
      and coronary artery disease in various population studies. The aim of this study
      is to assess the relationship between eNOS 4a/b polymorphism and premature CAD.
      MATERIAL AND METHODS: A total of 70 patients under age 35 who presented with ST
      segment elevation myocardial infarction (STEMI) were included in this study.The
      control group included 50 age- and gender-matched subjects with normal coronary
      arteries on angiography.The eNOS 4a/b polymorphism was assessed with polymerase
      chain reaction (PCR).The frequencies of eNOS 4a/b genotypes and alleles were
      compared. Multivariate regression analysis was used for estimation of the
      independent predictors of premature CAD. RESULTS: Frequency of eNOS4a/b gene, aa
      and ab genotypes were significantly higher in STEMI patients when compared to
      control group. Presence of allele'a'of the eNOS gene was an independent predictor
      of STEMI in a young population (OR: 2.78 95% CI: 1.02-7.56 P = 0.044). A
      significant correlation of eNOS gene polymorphism with other clinical properties
      of subjects was not established. CONCLUSION: The eNOS4a/b gene polymorphism may
      be associated with early development of atherosclerosis and myocardial infarction
      possibly secondary to deterioration of the endothelial function.

PMID- 24283107
TI  - Evaluation of the cost of atrial fibrillation during emergency hospitalization.
AB  - OBJECTIVE: The number of hospitalizations for atrial fibrillation has increased
      dramatically. This increase, in the number of hospital stays will continue, given
      the growth projections based on epidemiological data, and will contribute to
      significantly increase expenses for the social security system.The objective of
      this study was to evaluate the length of hospital stay, the average cost borne by
      social security, and the types of hospital stay expenditures for patients
      admitted through the emergency department for atrial fibrillation. METHODS:
      Patients were identified by using the minimal clinical summaries of seven general
      hospitals in Belgium in 2008. Only hospitalized patients having as primary
      diagnosis code ICD-9-CM 42731 'atrial fibrillation'were selected for this study.
      Hospital billing files were analysed in order to isolate the costs borne by
      social security. Outliers were isolated in order not to have results influenced
      by patients having an atypical length of stay. RESULTS: Results show that the
      mean length of stay was 8.6 days and the mean cost charged to social security was
      euro 3,066.02 per hospital stay.The mean cost of care was strongly associated
      with the degree of severity index related to the APR-DRG. Approximately 85% of
      the total cost was related to the cost of hospital days and medical procedures
      with medical imaging and laboratory tests being the two main cost inductors. 18%
      of patients had cardioversion during their hospital stay, including 4% who had
      only that treatment. 19% of patients used amiodarone. Flecainide and propafenone
      were also used, but less frequently. CONCLUSIONS: The mean cost of care for AF
      patients admitted via the emergency department is strongly associated with the
      degree of severity. Approximately 85% of the total cost is related to the cost of
      hospital days and medical procedures. Hypertension is the most common secondary
      diagnosis. An optimal treatment of this risk factor could help to reduce the risk
      of atrial fibrillation, and thereby reduce the morbidity and costs associated
      with this disease.

PMID- 24283108
TI  - Elite athletes with mitral or aortic regurgitation and their cardiopulmonary
      capability.
AB  - BACKGROUND: Aortic or mitral valvular regurgitation (left cardiac valvular
      regurgitation, LCVR) of less than second-degree (< degree II) occasionally found
      in competitive athletes is of questionable relevance. Precisely detectable by
      echocardiography there is scarce published data that clarifies cardiopulmonary
      capacity or any limitations LCVR < degree ll may cause. METHODS: In this single
      centre study we consecutively recruited highly trained athletes (n= 14) with LCVR
      < degree ll detected in 2D echo. Not included were athletes with multi- or right
      cardiac valvular dysfunction and structural heart disease other than bicuspid
      aortic valve or mitral valve prolaps. Target parameters were determined by 2D
      echo and spiroergometry. RESULTS: There were no significant differences with
      regard to age and body mass index. Echocardiographically determined muscle mass
      index was increased in both groups (134 14.7 vs 129.6+/-27.5; P=0.69), whereas
      the left-ventricular end-diastolic diameter index was significant higher in the
      LCVR < degree II group (27.3 +/- 1.3 vs 25.2 +/- 2.4; P = 0.04). However, there
      were no significant differences with regard to (oxygen uptake) V02, at baseline
      (athletes with LCVR < degree II 5.7 +/- 0.9 vs controls 5 +/- 0.96, P= 0.06), at
      the anaerobic threshold (athletes with LCVR < degree II 47.3 +/-8.4 vs controls
      47.4 +/- 5, P= 0.97) and maximally (VO2max; athletes with LCVR < degree II 57.7
      6.3 vs controls 57.1 +/- 5.1, P= 0.81). Neither levels of lactate nor of brain
      natriuretic peptide differed significantly. CONCLUSION: High level athletes
      presenting with aortic or mitral regurgitation < degree II in are not
      disadvantaged with regard to their cardiopulmonary capability.

PMID- 24283109
TI  - Independent risk factors for morphological abnormalities of the internal carotid
      artery.
AB  - PURPOSE: Whether carotid abnormalities (CAs) are congenital or acquired, and
      whether they are risk factors for cerebrovascular diseases or medical
      curiosities, is still under debate. The aim of this study was to identify the
      independent risk factors for CAs. METHODS: In this study, subjects (aged 3 days
      to 102 years) were divided into nine age groups, divided by 10-year intervals.
      The observed CAs were prospectively classified, according to the nature of the
      abnormality. Analyses of the factors associated with CAs were performed by
      univariate and multivariate logistic regression models. RESUITS: Of the 1,838
      internal carotid arteries studied, 552 had CA (30%). There were peaks in the
      prevalence of CA in the 0-9-year-old group and in the above 80 years group; the
      lowest rate was found among the subjects in the 20-39-year-old group. The
      significant predictors of CA were age (OR 1.986, in the60-69-year-old group; OR
      2.283, in the 70-79-year-old group; and OR 3.566, in the > 80-year-old group vs
      the 40-49-year-old group reference group), female gender (OR 1.799), hypertension
      (OR 1.52), and carotid artery atherosclerosis (OR3.176). CAs in youngersubjects
      were also associated with age (OR 9.894 in the 0-9-year-old group; and OR 3.294
      in the 10-19-year-old group vs the 30-39-year-old group reference group).
      CONCLUSIONS: Both congenital and acquired factors may be involved in CAs. In
      subjects> or = 40years old, CAs seem to be more associated with acquired factors,
      including ageing, gender, hypertension, and atherosclerosis.

PMID- 24283110
TI  - Rosuvastatin versus atorvastatin to prevent contrast induced nephropathy in
      patients undergoing primary percutaneous coronary intervention (ROSA-cIN trial).
AB  - AIM: We aimed to compare the incidence of contrast-induced nephropathy (CIN)
      between atorvastatin versus rosuvastatin in patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing primary coronary angioplasty. METHODS:
      One hundred ninety-two consecutive patients, who underwent primary percutaneous
      intervention (p-PCI) with the diagnosis of STEMI, were included in the study. The
      patients were randomized to take atorvastatin 80 mg (n=98) or rosuvastatin 40 mg
      (n= 94) before the procedure. Biochemical and complete blood count measurements
      were done at baseline and at 48 hours following admission. RESULTS: The incidence
      of CIN was 8.9% (n= 17) in the entire groups. The analysis performed between the
      statin groups revealed no statistical difference in any of the renal dysfunction
      indicators [baseline creatinine, baseline estimated glomerular filtration rate
      (eGFR), creatinine at 48 h, eGFR at 48 h, difference between baseline and 48 h
      creatinine, the per cent increase in the creatinine at 48 hours relative to basal
      creatinine]. In STEMI patients undergoing primary PCI, only the amount of the
      contrast agent administered was determined to be an independent predictor for CIN
      (OR and 95% CI: 1.08 (1.03- 1.13), P< or = 0.001). Left ventricular ejection
      fraction exhibited borderline statistical significance (OR and 95% CI: 0.88 (0.77
      1.01), P= 0.07). CONCLUSION: Atorvastatin and rosuvastatin had similar efficacy
      in preventing CIN in patients with STEMI undergoing P-PCI.

PMID- 24283111
TI  - Exercise intolerance in heart failure: update on exercise parameters for
      diagnosis, prognosis and therapeutic interventions.
AB  - Exercise intolerance is a hallmark feature of chronic heart failure and is
      associated with poor prognosis. This review provides an update on cardiopulmonary
      exercise variables, proven to be prognostically important in heart failure.
      Besides the widely accepted peak oxygen consumption (peak VO2) and VEN/VCO2
      slope, other exercise variables - exercise oscillatory ventilation (EOV) and
      partial pressure of end-tidal CO2, (PETCO2) - should gain attention in the
      interpretation of cardiopulmonary exercise testing. In addition to prognosis, the
      pathophysiological origin is also discussed. Different mechanisms underlie these
      exercise variables with an important contribution of haemodynamic, pulmonary and
      peripheral abnormalities. Given the different pathophysiological origin, a
      multivariate assessment with the inclusion of all the aforementioned parameters
      should be encouraged, not only for diagnostic and prognostic purposes but also
      for evaluating the effect of interventions.

PMID- 24283112
TI  - Malignant cardiac tamponade.
AB  - Malignant pericardial effusion is a frequent complication in primary mediastinal
      and pleural malignancies. As a first manifestation of a malignant tumour,
      however, it is rare. With cardiac tamponade the likelihood of malignancy
      increases. We report a life-threatening cardiac tamponade as the primary clinical
      presentation of a pericardial mesothelioma. Pericardiocentesis resolved the acute
      symptoms, followed by surgical pericardial fenestration. Oncologic therapy is
      evidently indicated. All mesotheliomas carry a poor prognosis.

PMID- 24283113
TI  - Percutaneous revascularization of anomalous left main coronary artery stenosis
      with a retro-aortic course.
AB  - We described the rare case of a 54-year-old male patient with an anomalous left
      main coronary artery, originating from the right sinus with a retro-aortic
      course. A significant distal left main coronary artery (LM) atherosclerotic
      lesion was identified and a successful PCI with direct stenting was performed.
      Coronary artery abnormalities represent the most technically challenging cases
      for interventional cardiologists. However, in selected cases, a percutaneous
      intervention can offer an effective and safe therapeutic option.

PMID- 24283114
TI  - Long-term conservative management of a giant cardiac fibroma.
AB  - A giant cardiac fibroma was discovered during evaluation for a soft systolic
      murmur in an asymptomatic 2-week-old girl. Echocardiography and magnetic
      resonance imaging showed a large intraventricular solid mass developed at the
      expense of the left ventricular lateral wall. Tumour progression resulted in
      failure to thrive and ventricular arrhythmia between 2 and 18 months of age. At
      that time, complete resection seemed unfeasible and conservative management with
      heart failure and antiarrhythmic medications was chosen. All drugs were
      discontinued when the patient was 5 years old. Since that time, the mass is
      stable and the patient is strictly asymptomatic. Conservative strategy seems to
      be acceptable in selected cases but close follow-up is mandatory.

PMID- 24283115
TI  - Fondaparinux in heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia is a potentiallylife-threatening complication of
      heparin or low-molecular-weight heparin administration. We describe the case of a
      patient with heparin-induced thrombocytopenia complicated by pulmonary embolism,
      successfully treated with fondaparinux, a factor Xa inhibitor. We also review the
      literature regarding the use of this anticoagulant in heparin-induced
      thrombocytopenia complicated by thrombosis. Few treatment options are available
      in Belgium, and there is little evidence regarding newer anticoagulants.

PMID- 24283116
TI  - Brugada syndrome presenting as an acute coronary syndrome.
AB  - Syncope, non-specific ST-segment alterations and elevated troponin (cTn) are
      suspicious of an acute coronary syndrome (ACS). While an ACS is excluded when the
      coronary angiogram returns normal, the raised cTn should prompt a search for
      other potentially lethal diseases, such as pulmonary embolism, myocarditis or
      malignant ventricular arrhythmias. Here we describe a 42-year-old man presenting
      with syncope, ST-segment elevation, cTn rise and a normal angiogram. He was
      ultimately diagnosed with Brugada syndrome.

PMID- 24283117
TI  - Failed thrombin treatment due to patent collateral leakage after refractory
      guidewire-induced coronary artery perforation.
AB  - Ellis class III coronary artery perforation is a rare but catastrophic
      complication associated with high mortality and poor outcome of percutaneous
      coronary intervention. We describe a case of coronary artery perforation caused
      by a stiff hydrophilic guidewire during percutaneous coronary intervention.
      Leakage from patent collaterals continued despite successful embolism of the
      perforated artery. Although he underwent cardiac surgery, the patient died due to
      the rupture of a left ventricular pseudoaneurysm.

PMID- 24283118
TI  - Large-vessel giant cell arteritis fever of unknown origin in a patient with a
      prosthetic valve.

PMID- 24283119
TI  - An enormous left coronary system related to a giant fistula between the
      circumflex coronary artery and the coronary sinus.

PMID- 24283120
TI  - Fostering diffusion of scientific contents of national society cardiovascular
      journals: the new ESC search engine.
AB  - European Society of Cardiology (ESC) National Society Cardiovascular Journals
      (NSCJs) are high-quality biomedical journals focused on cardiovascular diseases.
      The Editors' Network of the ESC devises editorial initiatives aimed at improving
      the scientific quality and diffusion of NSCJ. In this article we will discuss on
      the importance of the Internet, electronic editions and open access strategies on
      scientific publishing. Finally, we will propose a new editorial initiative based
      on a novel electronic tool on the ESC web-page that may further help to increase
      the dissemination of contents and visibility of NSCJs.

PMID- 24283121
TI  - Recent progress in the characterization of avian enteric viruses.
AB  - Despite the importance of the poultry gut, remarkably little is known about the
      complex gut microbial community. Enteric disease syndromes such as runting
      stunting syndrome in broiler chickens and poult enteritis complex in young
      turkeys are difficult to characterize and reproduce in the laboratory. A great
      deal of work has been done to characterize the bacterial population in the
      poultry gut, leading to useful performance-based interventions such as direct-fed
      microbial preparations. Advances in the application of rapid molecular
      diagnostics and the advent of the next generation of nucleic acid sequencing have
      allowed researchers to begin to decipher the microbial community in complex
      environmental samples. Researchers have made great strides recently in placing
      names to some of the unknown and undescribed small viruses in the poultry gut
      such as parvoviruses, picornaviruses, picobirnavirus, and calicivirus.
      Investigation into the novel avian astroviruses continues, and recent progress
      has been made in the molecular characterization of the avian rotaviruses. This
      review will focus on the recent advances that have been made in the discovery,
      description, and characterization of the multitude of viruses that reside in the
      poultry gut.

PMID- 24283122
TI  - Variation in the responses of wild species of duck, gull, and wader to
      inoculation with a wild-bird-origin H6N2 low pathogenicity avian influenza virus.
AB  - There is poor understanding of host responses to avian influenza virus (AIV)
      infection in wild birds, with most experimental studies using captive-bred birds
      and highly pathogenic AIVs that have an early endpoint. The objective of this
      study was to experimentally assess antibody responses and patterns of viral
      excretion in wild birds challenged with a low pathogenicity AIV. Ruddy turnstones
      (Arenaria interpres), silver gulls (Chroicocephalus novaehollandiae), and
      wandering whistling ducks (Dendrocygna arcuata) were challenged with a H6N2
      virus, and blood, cloacal, and oropharyngeal (OP) swabs were analyzed from each
      bird over 28 days, with serology conducted on the ducks for a further 7 mo.
      Nineteen of 22 birds showed evidence of infection, with respiratory infection
      prevalent in the turnstones and gulls as mostly low titer viral excretion to 4
      days postinoculation (DPI) with gastrointestinal replication detected in only one
      turnstone. In AIV naive ducks, there was gastrointestinal tropism with moderately
      high titer viral excretion via the cloaca to 6 DPI and low-grade OP viral
      excretion to 4 DPI. The hemagglutination inhibition antibody response was poor in
      the ducks, declining from 19 to 56 DPI, with higher titer responses in the gulls
      and turnstones. All infected birds responded with elevated nucleoprotein
      antibodies (in competitive enzyme-linked immunosorbent assay) by 7-10 DPI, and in
      the ducks these waned slowly after 42 DPI and were long-lived to at least 8 mo.
      The interspecies variability in response was consistent with a subtype that had
      adapted well in ducks, while the response of the turnstones may have been
      influenced by preexisting immunity to AIV. These findings provide insight into
      AIV infection dynamics in wild birds and highlight the need for further research.

PMID- 24283123
TI  - Prevalence and differentiation of diseases in Maryland backyard flocks.
AB  - Several epidemiologic surveillance studies have implicated backyard flocks as a
      reservoir for poultry diseases; however, much debate still exists over the risk
      these small flocks pose. To evaluate this concern, the prevalence of Newcastle
      disease (ND), infectious laryngotracheitis (ILT), Mycoplasma gallisepticum (MG),
      and Salmonella was determined in 39 Maryland backyard flocks. Serum, tracheal,
      and cloacal swabs were randomly collected from 262 birds throughout nine counties
      in Maryland. Through PCR and ELISA analysis, disease prevalence and
      seroprevalence were determined in flocks, respectively, for the following: ND
      (0%, 23%); ILT (26%, 77%); MG (3%, 13%); and Salmonella (0%, not done). Vaccine
      status could not be accurately confirmed. Premise positives were further
      differentiated and identified by partial nucleotide sequencing. Screening of the
      10 ILT premise positives showed that most were live attenuated vaccines: eight
      matched a tissue culture origin vaccine, one matched a chicken embryo origin
      (CEO) vaccine, and one was CEO related. The single MG-positive flock, also
      positive for the CEO-related sequence, was identified as the infectious S6
      strain. The prevalence rates for these economically important poultry diseases
      ranged from none to relatively low, with the vast majority of sampled flocks
      presenting no clinical signs.

PMID- 24283124
TI  - Development and validation of one-step SYBR green real-time RT-PCR for the rapid
      detection of newly emerged duck Tembusu virus.
AB  - Duck Tembusu virus (DTMUV) is a single-stranded positive-sense RNA virus that
      causes disease to emerge in duck flocks and results in huge economic losses to
      the duck industry. However, no vaccines and control measures are available in
      China to date. Development of reliable and fast detection methods is necessary to
      prevent and control this disease. Therefore, a one-step SYBR Green real-time
      reverse transcription polymerase chain reaction (RT-PCR) method is established
      here for DTMUV detection. The results show that the method can specifically
      detect DTMUV without cross-reactions with selected avian pathogens. The
      sensitivity of the assay was 1000 times greater than that of a conventional RT
      PCR and able to test as few as 20 copies from RNA standard samples. The
      coefficients of variations of inter- and intra-assay values ranged from 0.09% to
      0.36% and 0.1% to 0.23%, respectively. Testing 168 field samples and 96
      experimentally infected samples by conventional RT-PCR and the one-step SYBR
      Green real-time RT-PCR, the positive rates were 35.1% and 73.8% from field
      samples and 30.2% and 64.6% from infected samples. The one-step SYBR Green real
      time RT-PCR developed in this study was shown to be a sensitive, specific, high
      throughput, cost-effective, and simple diagnostic tool for the rapid detection
      and epidemiological surveillance of the emerging DTMUV infection.

PMID- 24283125
TI  - Molecular and phenotypic characterization of Escherichia coli isolated from
      broiler chicken flocks in Egypt.
AB  - Avian pathogenic Escherichia coli (APEC) infection is responsible for great
      economic losses to the poultry industry worldwide and there is increasing
      evidence of its zoonotic importance. In this study, 219 E. coli isolates from 84
      poultry flocks in Egypt, including 153 APEC, 30 avian fecal E. coli (AFEC), and
      36 environmental E. coli, were subjected to phylogenetic grouping and virulence
      genotyping. Additionally, 50 of these isolates (30 APEC from colisepticemia and
      20 AFEC) were subjected to a more-extensive characterization which included
      serogrouping, antimicrobial susceptibility analysis, screening for seven
      intestinal E. coli virulence genes (stx1, stx2, eae, espP, KatP, hlyA, and
      fliCh7), multilocus sequence typing (MLST), pulsed-field gel electrophoresis
      (PFGE), and in vivo virulence testing. More than 90% of the total APEC examined
      possessed iroN, ompT, hlyF, iss, and iutA, indicating that Egyptian APECs, like
      their counterparts from the United States, harbor plasmid pathogenicity islands
      (PAIs). The majority of APEC and AFEC were of phylogenetic groups A, B1, and D.
      For the 50-isolate subgroup, more than 70% of APEC and 80% ofAFEC were multidrug
      resistant. Among the subgroup of APEC, MLST analysis identified 11 sequence types
      (ST) while seven STs were found among AFEC. Based on PFGE, the genetic
      relatedness of APEC and AFEC ranged from 50%-100% and clustered into four primary
      groups at 50% similarity. Two of the eight APEC strains tested in chickens were
      able to induce 25% mortality in 1-day-old chicks. APECs were distinguished from
      AFECs and environmental E. coli by their content of plasmid PAI genes, whereas
      APEC isolated from colisepticemia and AFEC were not distinguishable based on
      their antimicrobial resistance patterns, as both groups were multidrug resistant.
      Avian E. coli strains from broiler flocks in Egypt show similar sequence types to
      E. coli associated with human infection.

PMID- 24283127
TI  - Protecting chickens against coccidiosis in floor pens by administering Eimeria
      oocysts using gel beads or spray vaccination.
AB  - Control of avian coccidiosis is increasingly being achieved by the administration
      of low doses of Eimeria oocysts to newly hatched chicks. The purpose of this
      study was to test the efficacy of gel beads containing a mixture of Eimeria
      acervulina, Eimeria maxima, and Eimeria tenella oocysts as a vaccine to protect
      broilers raised in contact with litter. Newly hatched chicks were either sprayed
      with an aqueous suspension of Eimeria oocysts or were allowed to ingest feed
      containing Eimeria oocysts-incorporated gel beads. Control, 1-day-old chicks were
      given an equivalent number of Eimeria oocysts (10(3) total) by oral gavage or
      received no vaccine (nonimmunized controls). All chicks were raised in floor-pen
      cages in direct contact with litter. At 4 wk of age, all chickens and a control
      nonimmunized group received a high-dose E. acervulina, E. maxima, and E. tenella
      challenge infection. Chickens immunized with Eimeria oocysts in gel beads or by
      spray vaccination displayed significantly (P < 0.05) greater weight gain (WG)
      compared to nonimmunized controls. Feed conversion ratio (FCR) also showed a
      significant (P < 0.05) improvement in both groups relative to nonimmunized
      controls. Moreover, WG and FCR in both groups was not significantly different (P
      > 0.05) from chickens immunized by oral gavage or from nonimmunized, noninfected
      controls. Oocyst excretion after Eimeria challenge by all immunized groups was
      about 10-fold less than in nonimmunized controls. These findings indicate that
      immunization efficacy of gel beads and spray vaccination is improved by raising
      immunized chicks in contact with litter.

PMID- 24283126
TI  - Modeling the association of space, time, and host species with variation of the
      HA, NA, and NS genes of H5N1 highly pathogenic avian influenza viruses isolated
      from birds in Romania in 2005-2007.
AB  - Molecular characterization studies of a diverse collection of avian influenza
      viruses (AIVs) have demonstrated that AIVs' greatest genetic variability lies in
      the HA, NA, and NS genes. The objective here was to quantify the association
      between geographical locations, periods of time, and host species and pairwise
      nucleotide variation in the HA, NA, and NS genes of 70 isolates of H5N1 highly
      pathogenic avian influenza virus (HPAIV) collected from October 2005 to December
      2007 from birds in Romania. A mixed-binomial Bayesian regression model was used
      to quantify the probability of nucleotide variation between isolates and its
      association with space, time, and host species. As expected for the three target
      genes, a higher probability of nucleotide differences (odds ratios [ORs] > 1) was
      found between viruses sampled from places at greater geographical distances from
      each other, viruses sampled over greater periods of time, and viruses derived
      from different species. The modeling approach in the present study maybe useful
      in further understanding the molecular epidemiology of H5N1 HPAI virus in bird
      populations. The methodology presented here will be useful in predicting the most
      likely genetic distance for any of the three gene segments of viruses that have
      not yet been isolated or sequenced based on space, time, and host species during
      the course of an epidemic.

PMID- 24283128
TI  - Reduction of Salmonella enteritidis number after infections by immunization of
      liposome-associated recombinant SefA.
AB  - In order to generate Salmonella enterica serovar Enteritidis (Salmonella
      Enteritidis) fimbriae, SEF14, the sefA gene, which encodes the main subunit of
      the SEF14 fimbrial protein, was amplified from Salmonella Enteritidis by
      polymerase chain reaction (PCR) and subcloned into a prokaryotic expression
      vector pET-28a(+) to yield pET-28a(+)-sefA. The recombinant SefA (rSefA) protein
      was highly expressed and purified by nickel-affinity chromatography. Liposome
      associated rSefA was prepared for oral immunization to seek protective efficacy
      for intestinal infection with Salmonella Enteritidis. The titers of the IgG and
      IgA in the intestinal mucus were 1:256 and 1:512, respectively. Moreover, the
      titers of IgG and IgA in the sera were 1:256 and 1:128, respectively. Two weeks
      after the booster immunization, the chickens were challenged orally with 2 x
      10(6) colony-forming units (CFUs) of live Salmonella Enteritidis, and fecal
      samples were examined for bacterial excretion from the intestinal tract.
      Significantly less fecal excretion of bacteria was observed in immunized chickens
      for 4 wk after challenge. The numbers of bacteria in the intestinal contents
      (cecum and rectum) were also significantly reduced in immunized chickens, in
      contrast with the unimmunized controls. Oral immunization with liposome
      associated rSefA therefore elicits both systemic and mucosal antibody responses
      and results in reduced bacterial colonization in the intestinal tract and reduced
      excretion of Salmonella Enteritidis in the feces.

PMID- 24283129
TI  - Estimation of the prevalence of Salmonella species on the slatted area compared
      to the scratch area of broiler breeder chicken houses.
AB  - With the objective of detecting Salmonella species in the poultry house
      environment, sampling broiler breeder houses in the two-thirds slatted area and
      the one-third scratch area with pine shavings bedding can be difficult. The
      slatted area is where the females, consisting of approximately 90% of the
      population, eat, drink, and spend the majority of their time. The scratch area is
      where the males eat and drink, as well as where mating and mortality occur.
      Besides the nest boxes, the female feeders and water lines make the slatted areas
      more difficult to sample. However, it is important to take samples from the area
      with the greatest likelihood of isolating Salmonella. Therefore, boot swab
      samples were collected from 21 commercial broiler breeder chicken houses
      representing three different companies in north Georgia to estimate the
      prevalence of Salmonella on the slat vs. the scratch area in each chicken house.
      Every house sampled had a central scratch area covered with litter and two
      elevated slat areas constructed of wood. Four boot swab samples were collected on
      each side slat area by walking the entire length of the house for each swab.
      Eight samples were collected in the same manner from the scratch area. Results of
      335 total samples were acquired, 167 of which were obtained from the slat area
      and 168 of which came from the scratch area, yielding 242 total Salmonella
      isolations. Salmonella was found in 117 of the slat samples, representing 70.1%,
      compared to 125 of the scratch area samples, representing 74.4%. Both the
      univariate (P = 0.311) and the multivariable (P = 0.303) analysis showed that
      sampling location was not associated with Salmonella prevalence.

PMID- 24283130
TI  - Effects of broiler feed medications on Salmonella.
AB  - This pilot analysis was conducted with data from 52 conventional grow-out broiler
      flocks in a prospective field observational study in the southeastern United
      States during 2003-2006. Each flock was sampled for Salmonella 1 wk before the
      end of grow-out, upon arrival at the processing plant, and during processing
      (prior to and immediately after carcass chilling). The broiler litter was sampled
      on the day of bird harvest. The grow-out feeding programs, including the
      medications delivered in feed, were surveyed with questionnaires completed by the
      broiler managers and feedmill managers. Each detail of the feeding program was
      tested for statistical association with the frequency of Salmonella in the flock
      at each sampling point, after accounting for variation in Salmonella frequency
      between the farms, broiler complexes, and companies. Significant associations
      were found between Salmonella frequency in the broiler flock pre- and postharvest
      and the inclusion of feeds containing individual coccidiostats and other
      antimicrobial growth promoters, days on feed, and total consumption of feeds
      containing these products, as well as with practices such as a mash feed and a
      nonmedicated withdrawal feed. The analysis provided testable hypotheses for how
      broiler feed medications impact the frequency of Salmonella in the flocks.

PMID- 24283131
TI  - Aerosol transmission of an avian influenza H9N2 virus with a tropism for the
      respiratory tract of chickens.
AB  - A low pathogenic avian influenza virus (LPAI H9N2) was administered to 3-wk-old
      chickens by aerosol exposure, intranasal inoculation, and by oral inoculation.
      Tests for virus were by in ovo assay and by real-time reverse-transcriptase PCR.
      The aerosol dosage was determined by aerosolizing virus into a chamber when it
      was empty and when it contained chickens. Air was collected and the amount of
      virus inhaled was estimated to be about 18% of the total body uptake. In
      transmission studies, tests for virus were conducted on oropharyngeal or cloacal
      swabs. The 50% infectious dose (ID50) for aerosolized virus was about 2 log 10
      and 5 log 10 lower than by nasal or oral inoculation, respectively. The recovery
      rate was higher from swabs of the oropharyngeal region than from the cloacal
      region (P < 0.05). For horizontal transmission studies, uninfected chickens were
      held in isolators with seeders that had been inoculated intranasally with the
      H9N2 virus. Chickens exposed by indirect contact were separated by screens from
      the seeders. In another isolator those directly exposed were intermingled with
      the seeders. During the 10-day test period, none of the chickens developed
      symptoms of disease, but infection was detected as early as 4 and 7 days in the
      indirectly and directly exposed groups, respectively. These findings suggested
      that aerosol transmission of viruses similar to LPAI H9N2 could efficiently
      occur, at least over short distances.

PMID- 24283132
TI  - Effect of coronavirus infection on reproductive performance of turkey hens.
AB  - Turkey coronavirus (TCoV) infection causes enteritis in turkeys of varying ages
      with high mortality in young birds. In older birds, field evidence indicates the
      possible involvement of TCoV in egg-production drops in turkey hens. However, no
      experimental studies have been conducted to demonstrate TCoV pathogenesis in
      turkey hens and its effect on reproductive performance. In the present study, we
      assessed the possible effect of TCoV on the reproductive performance of
      experimentally infected turkey hens. In two separate trials, 29- to 30-wk-old
      turkey hens in peak egg production were either mock-infected or inoculated orally
      with TCoV (Indiana strain). Cloacal swabs and intestinal and reproductive tissues
      were collected and standard reverse-transcription PCR was conducted to detect
      TCoV RNA. In the cloacal swabs, TCoV was detected consistently at 3, 5, 7, and 12
      days postinoculation (DPI) with higher rates of detection after 5 DPI (> 90%).
      All intestinal samples were also positive for TCoV at 7 DPI, and microscopic
      lesions consisting of severe enteritis with villous atrophy were observed in the
      duodenum and jejunum of TCoV-infected hens. In one of the trials TCoV was
      detected from the oviduct of two birds at 7 DPI; however, no or mild microscopic
      lesions were present. In both experimental trials an average of 28%-29% drop in
      egg production was observed in TCoV-infected turkey hens between 4 and 7 DPI. In
      a separate trial we also confirmed that TCoV can efficiently transmit from
      infected to contact control hens. Our results show that TCoV infection can affect
      the reproductive performance in turkey hens, causing a transient drop in egg
      production. This drop in egg production most likely occurred as consequence of
      the severe enteritis produced by the TCoV. However, the potential replication of
      TCoV in the oviduct and its effect on pathogenesis should be considered and
      further investigated.

PMID- 24283134
TI  - Development of real-time polymerase chain reaction assay for detection of
      Ornithobacterium rhinotracheale in poultry.
AB  - Ornithobacterium rhinotracheale (ORT) is an emerging bacterium causing severe
      economic losses in poultry mostly due to respiratory and locomotory disturbances.
      Due to the fastidious nature of the organism, ORT is often overgrown by faster
      growing commensal and pathogenic bacteria. In this study we developed a real-time
      polymerase chain reaction (qPCR) assay for rapid and sensitive detection of ORT
      in samples collected from chickens and turkeys. The qPCR assay developed was able
      to detect 17 reference strains of ORT (serotypes A to Q) tested in this study,
      and no false-positive results were obtained from other organisms associated with
      respiratory tract infections. The qPCR assay was 100 times more sensitive than
      the modified conventional PCR. Using tenfold serial dilutions of the recombinant
      plasmid DNA containing the target gene fragment, the detection limit of the qPCR
      was estimated to be > or = 100 plasmid copies per reaction. Out of 42 examined
      poultry flocks, 26 cases were tested positive by both assays. The qPCR assay
      reduces turnaround time to about 2 hr, two times faster than the modified
      conventional PCR.

PMID- 24283133
TI  - Low pathogenic influenza A virus activity at avian interfaces in Ohio zoos, 2006
      2009.
AB  - This investigation to examine influenza A virus activity in avian species at four
      Ohio zoos was initiated to better understand the ecology of avian-origin
      influenza A (AIV) virus in wild aquatic birds and the possibility of spill-over
      of such viruses into captive zoo birds, both native and foreign species. Virus
      isolation efforts resulted in the recovery of three low pathogenic (LP) AIV
      isolates (one H7N3 and two H3N6) from oral-pharyngeal or cloacal swabs collected
      from over 1000 zoo birds representing 94 species. In addition, 21 LPAIV isolates
      possessing H3N6, H4N6, or H7N3 subtype combinations were recovered from 627
      (3.3%) environmental fecal samples collected from outdoor habitats accessible to
      zoo and wild birds. Analysis of oral-pharyngeal and cloacal swabs collected from
      free-ranging mallards (Anas platyrhynchos) live-trapped at one zoo in 2007
      resulted in the recovery of 164 LPAIV isolates (48% of samples) representing five
      HA and six NA subtypes and at least nine HA-NA combinations. The high frequency
      of isolate recovery is undoubtedly due to the capture and holding of wild ducks
      in a common pen before relocation. Serologic analyses using an agar gel immune
      diffusion assay detected antibodies to the influenza A virus type-specific
      antigen in 147 of 1237 (11.9%) zoo bird sera and in 14 of 154 (9%) wild mallard
      sera. Additional analyses of a limited number of zoo bird sera demonstrated HA-
      and NA-inhibition activity to 15 HA and nine NA subtypes. The spectrum of HA
      antibodies indicate antibody diversity of AIV infecting zoo birds; however, the
      contribution of heterologous cross-reactions and steric interference was not
      ruled out. This proactive investigation documented that antigenically diverse
      LPAIVs were active in all three components of the avian zoologic-wild bird
      interfaces at Ohio zoos (zoo birds, the environment, and wild birds). The
      resulting baseline data provides insight and justification for preventive
      medicine strategies for zoo birds.

PMID- 24283135
TI  - Cross-protective immune responses elicited by a Korean variant of infectious
      bronchitis virus.
AB  - Infectious bronchitis virus (IBV) infections cause great economic losses to the
      poultry industry worldwide. IBVs continuously evolve by developing mutations in
      antigenic sites; therefore, an IBV vaccine that provides broad cross-protection
      can be a highly relevant and practical method in IBV control strategies. Although
      some IBV vaccine strains are known to provide protection against multiple IBV
      serotypes, in general commercially available IBV vaccine strains provide
      protection against antigenically related viruses but not distinct heterologous
      viruses. In the present study we characterized the Korean variant IBV K40/09
      strain with regard to its immunogenicity and protective efficacy against seven
      currently circulating IBV serotypes. Three-week-old specific-pathogen-free
      chickens were intraocularly immunized with the IBV K40/09 strain at 10(3.5) 50%
      egg infective dose (EID50). Three weeks after immunization all the birds were
      challenged with seven different strains at 10(4.5) EID50. Chickens immunized with
      the IBV K40/09 strain showed significantly high levels of protection against all
      challenge viruses at the trachea and kidney levels. Our results suggest that IBV
      K40/09 could be useful to ensure IBV vaccine effectiveness owing to its cross
      protective ability. Therefore, the IBV K40/09 strain merits consideration as a
      vaccine candidate to prevent infection as well as the spread of new IBV strains
      and many IBV variants that have been reported worldwide.

PMID- 24283136
TI  - Effect of spray Escherichia coli vaccine on the immunity of poultry.
AB  - Avian pathogenic Escherichia coli is a current problem in the poultry industry,
      causing mortality and economic losses. This paper evaluates the dynamics in
      immune response after the use of spray vaccination against E. coli and, thereby,
      seeks to understand how the vaccine can provide protection. During the early
      stages of response to vaccination the presence of antigen-presenting cells is
      predominant, but these diminish within the first 7 days after vaccination. The
      immune correlate of protection of vaccination using the E. coli vaccine Poulvac
      E. coli (aroA-deficient mutant strain) probably does not depend on the production
      of circulating antibodies (as assessed through the presence of B lymphocytes) and
      is linked to the presence of CD4+TCRVbeta1+. These cells act on mucosa tissue
      stimulating the production of immunoglobulin A. Vaccination stimulated a high
      state of immunocompetence, as assessed by measurement of several cellular
      subsets. This state of "immune alertness," however, may be associated with
      reduced weight gain. The high presence of naive and memory CD8 cells in the
      vaccinated group at 14 and 21 days postvaccination may indicate greater ability
      in the future to prevent tissue invasion by E. coli, based on the possibility
      that these cells will proliferate rapidly to a new stimulus. The simultaneous use
      of vaccine with the antibiotic ceftiofur sodium interferes with the immune
      response obtained through vaccination. In combination, the data obtained in this
      study indicate that the immune response produced by a spray vaccine against E.
      coli is mainly a cellular response, especially relevant to the sites in contact
      with the pathogen. It is suggested that there is a strong cell migration to the
      mucous membranes, where macrophages act first and then lymphocytes take part to
      protect the host. It is believed that recruited lymphocytes will act in the
      production of secreted IgA, which probably plays a greater role in the defense
      when compared with circulating immunoglobulins. The assessment of cellular
      dynamics by flow cytometry made it possible to elucidate the operation mechanism
      of the live E. coli vaccine.

PMID- 24283137
TI  - Isolation of influenza A viruses from wild ducks and feathers in Minnesota (2010
      2011).
AB  - We investigated the feasibility of testing feathers as a complementary approach
      to detect low pathogenic influenza A viruses (IAVs) in wild duck populations.
      Feathers on the ground were collected at four duck capture sites during 2010 and
      2011, in Minnesota, U. S. A. IAVs were isolated from both feathers and cloacal
      swabs sampled from ducks at the time of capture. Although virus isolation rates
      from feather and cloacal swabs were inconsistent between collections, the overall
      rate of isolation was greatest from the feather samples. Viruses isolated from
      feathers also reflected the subtype diversity observed in cloacal swab isolates
      but resulted in many more isolates that contained more than one virus. Our study
      suggests that testing feathers may represent an alternative noninvasive approach
      to recover viruses and estimate subtype abundance and diversity.

PMID- 24283138
TI  - Persistence of two Trichomonas gallinae isolates in chlorinated and distilled
      water with or without organic material.
AB  - Trichomonas gallinae is a protozoan parasite commonly found in columbids,
      passerines, and raptors. In passerines and columbids, trichomonosis causes
      significant morbidity and mortality associated with contaminated bird feeders and
      waters. However, there has been little work on the persistence of T. gallinae in
      water to determine if artificial waters are a likely source of infection for
      naive birds. To examine drinking water as a source of T. gallinae transmission,
      we inoculated 1 x 10(6) trichomonads into containers with 500 ml of either
      distilled or chlorinated water. In addition, we inoculated the same number of
      trichomonads in distilled or chlorinated water contaminated with 15 g organic
      matter. Aliquots of 0.5 ml were collected from each container at 0, 0.5, 1, 5,
      10, or 20 min; inoculated into a Trichomonas culture packet; and incubated at 37
      C for 6 days. Survival was best in the presence of organic matter, with either
      distilled or chlorinated water. Uncontaminated chlorinated water did not allow
      survival at any sampling period.

PMID- 24283139
TI  - Relative disease susceptibility and clostridial toxin antibody responses in three
      commercial broiler lines coinfected with Clostridium perfringens and Eimeria
      maxima using an experimental model of necrotic enteritis.
AB  - Necrotic enteritis is an enteric disease of poultry resulting from infection by
      Clostridium perfringens with coinfection by Eimeria spp. constituting a major
      risk factor for disease pathogenesis. This study compared three commercial
      broiler chicken lines using an experimental model of necrotic enteritis. Day-old
      male Cobb, Ross, and Hubbard broilers were orally infected with viable C.
      perfringens and E. maxima and fed a high-protein diet to promote the development
      of experimental disease. Body weight loss, intestinal lesions, and serum antibody
      levels against alpha-toxin and necrotic enteritis B-like (NetB) toxin were
      measured as parameters of disease susceptibility and host immune response. Cobb
      chickens exhibited increased body weight loss compared with Ross and Hubbard
      breeds and greater gut lesion severity compared with Ross chickens. NetB antibody
      levels were greater in Cobb chickens compared with the Ross or Hubbard groups.
      These results suggest that Cobb chickens may be more susceptible to necrotic
      enteritis in the field compared with the Ross and Hubbard lines.

PMID- 24283140
TI  - Mycobacterium avium subsp. avium found in raptors exposed to infected domestic
      fowl.
AB  - We report a case of a falcon breeding facility, where raptors (both diurnal and
      nocturnal) were raised in contact with domestic fowl (Gallus gallus f.
      domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental
      samples from 20 raptors and four common ravens (Corvus corax) were collected.
      Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle
      [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and
      little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the
      flock of domestic fowl and one of the infected raptors had the same origin
      (zoological collection), they might have had a common source of
      colonization/infection. However, the detection of M. a. avium in feces of three
      other raptors may point at transmission of the agent between the birds in the
      facility. Contact of raptors with domestic fowl infected by M. a. avium may pose
      a risk for transmission of the infection for them; however, raptors from the
      falcon breeding facility seemed to be relatively resistant to the infection.

PMID- 24283141
TI  - Genital form of pasteurellosis in breeding turkeys infected during artificial
      insemination and isolation of an unusual strain of Pasteurella multocida.
AB  - A genital and potentially fatal form of Pasteurella multocida infection was
      reported on two turkey-breeding farms on which birds were vaccinated against
      Pasteurella multocida. Both outbreaks were linked to the use of semen from young
      vaccinated toms with a history of respiratory pasteurellosis followed by
      treatment during rearing. Typing by agar gel immunodiffusion and rapid slide
      agglutination of P. multocida isolated from cloacal swabs was completed by
      multilocus sequence typing. Restriction enzyme analysis showed that that the
      isolates were clonal. They belonged to sequence type (ST) 30, described in
      chickens, cats, and ducks. This strain differed in sequence type from the ones
      used in the vaccine (ST8, ST60, ST53, and ST235), which might have limited its
      effectiveness. No contamination of the semen (n = 30) was found, suggesting fecal
      contamination during semen collection.

PMID- 24283142
TI  - Ulcerative enteritis-like disease associated with Clostridium sordellii in quail.
AB  - A natural outbreak of ulcerative enteritis-like disease associated with
      Clostridium sordellii was diagnosed in two commercial quail flocks. Clinical
      signs in the quail included anorexia, weakness, and increased mortality in the
      flocks. Lesions in the intestine were characterized by ulcers covered with
      fibrinonecrotic exudate in the small intestine and occasional hemorrhages. There
      were also multifocal pale areas of necrosis in the liver. Clostridium sordellii
      was isolated from the intestine and liver. A retrospective study of avian cases
      submitted to the California Animal Health and Food Safety Laboratories revealed
      that C. sordellii had been isolated in 45 avian submissions, most commonly in
      chickens and turkeys. In most of these cases the birds were diagnosed with
      necrotic enteritis, with or without hepatitis. Clostridium sordellii has
      occasionally been associated with gangrenous dermatitis in poultry, but this is
      the first report of enteritis in an avian species.

PMID- 24283144
TI  - The possibilities in change.

PMID- 24283143
TI  - Disseminated avian mycobacteriosis in a free-living grey heron (Ardea cinerea).
AB  - Wild birds share with humans the capacity for moving fast over large distances.
      During migratory movements, birds carry pathogens that can be transmitted between
      species. One of these concerning pathogens is Mycobacterium spp. A necropsy was
      performed in a grey heron (Ardea cinerea) that had been medically treated for a
      polyarthritic process. Grossly, firm white-yellowish nodules of various size,
      resembling granulomas, were observed in right carpal joint, both patellar joints,
      neck musculature, palate, pharynx, larynx, nasal sinuses, pericardial sac, air
      sacs, proventriculus and intestinal serosa, pancreas, kidneys, adrenal glands,
      and oviduct. Microscopically, these lesions were composed of multinucleated giant
      cells, large macrophages, and lymphocytes, with a central zone of necrosis and in
      some cases with peripheral fibrosis. Acid-fast bacilli were detected within these
      lesions. Lesions were cultured and Mycobacterium avium subsp. avium was
      identified. To the best of our knowledge this is the first description of
      mycobacteriosis in grey herons. Although the grey heron is currently considered a
      least-concern species, avian mycobacteriosis remains a threat on the conservation
      management of endangered avian species, and constitutes a public health concern
      as well.

PMID- 24283145
TI  - Turning awareness into advocacy.

PMID- 24283146
TI  - Selection bias.

PMID- 24283147
TI  - Never give up".

PMID- 24283148
TI  - Ketamine for acute-on-chronic pain.

PMID- 24283149
TI  - Prescription for physical activity a survey of Canadian nurse practitioners.
AB  - Although nurse practitioners are well placed to counsel patients about getting
      enough exercise, little abstract is known about their attitudes and practice in
      this area of health promotion. The authors used a self-administered Internet
      based questionnaire to explore how Canadian NPs perceive their competence in
      prescribing physical activity and the importance they ascribe to doing so.
      Participants were asked to identify factors that most commonly prompt physical
      activity prescription. Overall, the respondents felt fairly competent in their
      ability to prescribe physical activity (mean score 4.49/6.0, SD = .90) and felt
      that this function was important (mean score 4.82/6.0, SD = .85). Competence in
      prescribing physical activity and a perception that this intervention is
      important were both positively correlated with frequency of prescribing. The most
      commonly reported barrier to prescribing physical activity was a lack of time. On
      average, respondents prescribed physical activity to 59 per cent of their
      patients. The patient factors that most commonly prompted physical activity
      prescription were overweight or obesity, type 2 diabetes, hypertension and
      cardiovascular health. The lack of specific education in preventive medicine
      (e.g., obesity prevention, physical activity, nutrition) reported by 63 per cent
      of respondents points to the need for a physical activity prescription curriculum
      within nursing education to equip future NPs to respond to the high prevalence of
      physical inactivity in Canadian society.

PMID- 24283150
TI  - Getting your workplace immunization campaign track.

PMID- 24283151
TI  - Dance with me.

PMID- 24283152
TI  - A history-making practice: Hazel Booth can now put all her skills and expertise
      as an NP to use in Yukon.

PMID- 24283153
TI  - Paying it forward: why we need to support our profession and one another.

PMID- 24283154
TI  - Effect of poor motility on pregnancy outcome following intracytoplasmic sperm
      injection in couples whose male partners have subnormal hypo-osmotic swelling
      test scores.
AB  - PURPOSE: To determine the confounding effect, if any, of poor motility of sperm
      that are already compromised by an abnormal hypo-osmotic swelling (HOS) test on
      pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET) and
      intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: Clinical and live
      delivered pregnancy and implantation rates were retrospectively evaluated in
      first cycles of couples undergoing IVF-ET with ICSI where the HOS test was < 50%
      according to deciles of subnormal percentage motility (< 50%) and compared to
      those with normal motility > or = 50%. RESULTS: The combination of very poor
      motility and low HOS test scores did diminish pregnancy rates following IVF with
      ICSI. CONCLUSIONS: The only part of fertilization of the oocyte that ICSI does
      not overcome is phase 2 of oocyte activation. Based on these data, the
      combination of very low percentage motility and low HOS test scores do not
      adversely affect pregnancy outcome following IVF with ICSI.

PMID- 24283155
TI  - A comparison of three types of therapies for three different ovulation disorders
      in establishing pregnancies and evaluation of laboratory parameters that could
      influence the outcome.
AB  - PURPOSE: To evaluate the empirical use of progesterone (P) in the luteal phase
      for unexplained infertility. METHODS: Clinical and live-delivered pregnancy rates
      in three treatment cycles were compared in women with unexplained infertility vs
      women taking follicle maturing drugs for women completely anovulatory or those
      who release the oocyte before the follicle is mature. RESULTS: There was
      insufficient power to show a significant difference in the 19.5% live-delivered
      pregnancy rate found in women with a mean length of infertility duration of 2.1
      years who just used P in the luteal phase vs the 30.1% rate seen in women with
      clear-cut ovulatory defects treated with follicle-maturing drugs in the
      follicular phase and P in the luteal phase. CONCLUSIONS: Though a larger study
      would possibly show a lower pregnancy rate in those women with unexplained
      infertility empirically treated with P vs the women with ovulation defects, the
      empirical use of P allows easy treatment without the side-effects of follicle
      maturing drugs, e.g., hostile cervical mucus, vasomotor symptoms or ovarian
      cysts. The study was not designed to determine if empirical use of follicle
      maturing drugs with P support for unexplained infertility would be more effective
      than P supplementation alone.

PMID- 24283156
TI  - Effects of early-cleavage embryo transfer on in vitro fertilization-embryo
      transfer pregnancy outcomes.
AB  - PURPOSE: To observe the effects of early-cleavage embryo transfer (ET) on
      pregnancy outcomes in vitro fertilization-embryo transfer (IVF-ET). MATERIALS AND
      METHODS: The data of 6,548 two pro-nucleate (2PN) embryos and 968 patients who
      underwent IVF or intracytoplasmic sperm injection (ICSI) were analyzed. Of the
      968 cycles, early-cleavage embryos were used in 432 cycles (early-cleavage
      group), late-cleavage embryos were used in 246 cycles (late-cleavage group), and
      both early and late-cleavage embryos were used in 290 cycles (mixed group).
      RESULTS: High-quality embryo rate was significantly higher in early-cleavage
      group than in late-cleavage group (82.74% vs 59.83%; p < 0.01). Both clinical
      pregnancy and implantation rates in IVF or ICSI were significantly higher in
      early-cleavage group than in late-cleavage group (all p < 0.01). In ICSI, both
      clinical pregnancy and implantation rates were significantly higher in mixed
      group than in late-cleavage group (all p < 0.05). CONCLUSION: Early-cleavage ET
      can improve pregnancy outcomes in IVF or ICSI.

PMID- 24283157
TI  - Single curettage endometrial biopsy injury in the proliferative phase improves
      reproductive outcome of subsequent in vitro fertilization-embryo transfer cycle
      in infertile patients with repeated embryo implantation failure.
AB  - PURPOSE OF INVESTIGATION: To evaluate the effectiveness of single curettage
      endometrial biopsy injury (EBI) in the proliferative phase for in vitro
      fertilization-embryo transfer (IVF-ET) outcome of the subsequent cycle in
      infertile patients with repeated embryo implantation failure (EIF). MATERIALS AND
      METHODS: Of 89 patients who repeated EIF three times following transfer of
      morphologically good embryos and/or blastocysts, 40 patients chose curettage EBI
      prior to the subsequent IVF-ET cycle. Using a three-mm wide curette, EBI was
      performed once between days 6 and 12 of the spontaneous cycle. Their IVF-ET
      outcomes in the subsequent cycle were compared with those in 49 patients who did
      not opt for EBI. RESULTS: The clinical pregnancy rate (37.5% vs 12.2%), embryo
      implantation rate (23.6% vs 6.3%), and ongoing pregnancy rate (25.0% vs 8.2%)
      were significantly higher in the EBI group than in the non-EBI group. No serious
      complaints and complications were noted. CONCLUSION: Single curettage EBI in the
      proliferative phase of the preceding cycle significantly improved IVF-ET outcome
      in infertile patients with repeated EIF.

PMID- 24283158
TI  - Idiopathic premature ovarian failure: what is the most suitable ovarian
      stimulation protocol?
AB  - OBJECTIVE: To evaluate the ovarian response to ovarian stimulation in women with
      idiopathic premature ovarian failure (POF) in a prospective, controlled, and
      sequential crossover pilot study. MATERIALS AND METHODS: Ten women with
      idiopathic premature ovarian failure and normal karyotype were included in the
      study. Phase I was comprised of three consecutive control cycles consisting each
      of estrogen progestin sequential therapy. Phase II was comprised of three
      consecutive treatment cycles combining the use of gonadotropin-releasing hormone
      agonist (GnRHa) in the background of estrogen priming, followed by gonadotropin
      ovarian stimulation and corticosteroid immunosuppression. RESULTS: Ovulation
      rates in the treatment cycles (0/10; 0%) did not differ from control cycles
      (0/10; 0%). CONCLUSIONS: The findings of this pilot study showed that the
      combination of estrogen priming, corticosteroid immune-suppression, GnRHa
      pituitary desensitization, and followed by gonadotropin ovarian stimulation is
      ineffective in restoring ovarian function in women with idiopathic POF.

PMID- 24283159
TI  - Lipid peroxidation and antioxidant status in vagina microenvironment of patients
      with several common vaginitis.
AB  - OBJECTIVE: Oxidative stress has been suggested to play an important role in many
      diseases, including vaginitis. To evaluate oxidative biomarkers in the secretion
      of cervix samples of vaginitis, this study will illustrate the status of lipid
      peroxidation and antioxidant status in vaginal microenvironment. MATERIALS AND
      METHODS: A total of 257 patients with vaginitis, including candida vaginitis,
      bacterial vaginosis, and trichomonas vaginitis were involved in this study.
      Cervico-vaginal fluid was collected from these patients before and after
      treatment, and the malondialdehyde (MDA), catalase (CAT), superoxide dismutase
      (SOD), hydrogen peroxide (H2O2), and vitamin C levels were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: The results revealed that the MDA
      and H2O2 levels were increased in the vaginitis patients, while there was no
      significant difference in MDA level among different kinds of vaginitis before
      treatment. The CAT and vitamin C levels in vaginitis were decreased before
      treatment. Moreover, the data also showed that the MDA and H2O2 levels were
      decreased, while the CAT, SOD, and vitamin C levels were increased after received
      treatment, respectively, and there was no significant difference between controls
      and vaginitis. CONCLUSION: This study indicated that oxidative stress played an
      important role in vaginitis.

PMID- 24283160
TI  - Nonhormonal management of postmenopausal women: effects of a red clover based
      isoflavones supplementation on climacteric syndrome and cardiovascular risk serum
      profile.
AB  - PURPOSE OF INVESTIGATION: The aim of this prospective randomized study was to
      evaluate a red clover based isoflavones supplementation in the treatment of
      climacteric syndrome and its effects on cardiovascular risk serum profile.
      MATERIALS AND METHODS: The study included 150 healthy postmenopausal women that
      were randomly assigned to receive phytoestrogens tablets, amounting in a total
      daily intake of 60.8 mg red clover isoflavones plus 19.2 mg soy isoflavones (n =
      75), or placebo (n = 75). The authors evaluated teh following: daily number of
      hot flushes and Kupperman Index at baseline and after one and three months; serum
      total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol, triglycerides, prothrombin time (PT), partial thromboplastin time
      (PTT), fibrinogen, and antithrombin III (ATIII) at baseline and after three and
      six months. RESULTS: One hundred twenty-eight patients completed the study: 67 in
      the active group and 61 in the placebo group. The treatment led to a progressive
      significant reduction (p < 0.05) of the number of hot flushes in the active group
      compared to placebo already after one month, while Kupperman Index was
      statistically reduced after three months. No significant variation in total
      cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, PT, PTT,
      fibrinogen, and ATIII were found. CONCLUSION: The present findings suggest that a
      red clover based isoflavones supplementation in healthy postmenopausal women is
      promptly effective on climacteric syndrome, improves neurovegetative symptoms,
      safe on cardiovascular risk serum profile, and does not modify lipids and
      coagulation.

PMID- 24283161
TI  - Outcome in single and twin pregnancies at 20 to 24 weeks gestation: ten years
      experience in one perinatal center.
AB  - OBJECTIVE: The aim of this investigation was to evaluate the outcome at 20 to 24
      weeks gestation of twin and singleton extremely low birth weight infants. STUDY
      DESIGN: The authors conducted a retrospective cohort study of live newborns at 20
      to 24 weeks gestation admitted to one neonatal intensive care unit (NICU) from
      2000 to 2009. Outcome mortality and predictors of outcome were evaluated. Results
      were compared for twin and singleton infants. RESULTS: The cohort of infants
      consisted of 60 singleton infants and 17 twins. The results suggest an increased
      risk of death for twins when compared with singletons. A correlation between
      neonatal C-reactive protein (CRP) and bacterial culture positive results on
      admission to NICU might be a predictor of neonatal outcome. CONCLUSION: In
      extremely low birth weight infants, twin delivery is associated with an
      independent increased risk of death. Both first- and second-born twins are at
      increased risk.

PMID- 24283162
TI  - Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy:
      morphological aspects.
AB  - PURPOSE: To evaluate the morphological aspects in rats subjected to an
      association of the antiretroviral drugs zidovudine/lopinavir/ritonavir in
      different doses administered throughout the gestational period. MATERIALS AND
      METHODS: Forty pregnant rats were randomly allocated into four groups: control
      (Ctrl) and experimental (Exp1, Exp2, and Exp3), which received
      zidovudine/lopinavir/ritonavir in the doses of 10/13.3/3.3, 30/39.9/9.9, and
      90/119.7/29.7 mg/kg per day from the first to the 20th day of pregnancy,
      respectively. At term, the animals were euthanized and maternal and fetal organ
      samples were removed for morphological analysis. RESULTS: No major changes were
      identified in the group treated with the lowest dosing compared with the control.
      In group Exp2, the authors found hepatocytes with eosinophilic cytoplasm,
      pyknotic nuclei, and vasodilation. The proximal convoluted tubules of maternal
      kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of
      vasodilation. In the group treated with the highest dose (Exp3); the
      morphological changes in the maternal kidneys and livers were similar and more
      pronounced than those found in Exp2. The maternal pancreas of groups Exp2 and
      Exp3 evidenced moderate and progressive signs of tissue damage. The morphological
      features of all fetal livers, kidneys, and pancreases were normal. CONCLUSION:
      High doses of zidovudine/lopinavir/ritonavir association during the entire rat
      pregnancy period can cause definite morphological changes in maternal liver,
      kidneys, and pancreas. On the other hand, the corresponding fetal organs were not
      affected.

PMID- 24283163
TI  - De novo symptoms and their impact on life quality in patients following
      transvaginal reconstructive pelvic surgery with polypropylene mesh.
AB  - OBJECTIVE: To study the de novo symptoms and their impact on life quality in
      patients that underwent transvaginal reconstructive pelvic surgery (RPS) with
      polypropylene mesh. MATERIALS AND METHODS: From May 2004 to March 2011, 114
      severe pelvic organ prolapse (POP) patients with Stage III-IV by POP-Q system
      underwent RPS with polypropylene mesh. Patients completed pelvic floor distress
      inventory short form (PFDI-20) and pelvic floor impact questionnaire short form
      (PFIQ-7) preoperatively and repeated them at two and six months, and one year
      postoperatively. RESULTS: Ninety-six (84%, 96/114), 85 (75%, 85/114), and 77
      (68%, 77/114) patients, respectively, completed the questionnaires at two months,
      six months, and one year postoperatively. All patients had POP-Q staging scoring
      < or = I at one year after surgery. Nineteen (19.8%, 19/96) patients had mesh
      exposure at two and six months (7.8%, 6/77) at one year follow-up. Most vaginal
      and pelvic symptoms, urinary and obstructive defecation bothersome symptoms
      improved significantly at two months postoperatively and this improvement was
      maintained at the one year follow-up. Mean score of PFDI-20 and PFIQ-7 all
      improved significantly postoperatively at two and six months and at one year
      follow-up (p < 0.01). Fifty percent (48/96) of patients had postoperative de novo
      symptoms at the two months follow-up predominantly presented with bothersome
      vaginal discharge (35.4%, 34/96) and pelvic muscle symptoms (20.8%, 20/96).
      Patients with de novo symptoms had higher postoperative mean POPDI-6 and POPIQ-7
      scores (p < 0.05) than those without at the two month follow-up, but no
      significant difference was seen at the six month and at one year follow-ups.
      Patients with bothersome vaginal discharge had higher vaginal mesh exposure rate
      (41.2%, 14/34) than patients without (8.1%, 5/62) (p = 0.0003). One year after
      operation, 77 (68%) patients completed the non-validated satisfaction
      questionnaire. Seventy-four (96%, 74/77) patients said that they were either
      'very satisfied' or 'satisfied' with the outcome of their surgery, while three
      (4%, 3/77) reported unsatisfactory results. CONCLUSIONS: De novo symptoms were
      common after transvaginal RPS with polypropylene mesh, but most of them were
      moderate and resolved within six months postoperatively and seldomly had a long
      term negative impact on their quality of life. The impact of dyspareunia on
      patients' sexual function requires further research.

PMID- 24283164
TI  - Which factors may influence the duration of misoprostol-induced abortion in the
      second trimester?
AB  - BACKGROUND: To investigate the factors that may affect the time interval between
      induction and fetal expulsion in misoprostol-induced termination of second
      trimester pregnancy. MATERIALS AND METHODS: A retrospective analysis of second
      trimester pregnancies terminated in the second trimester between October 2008 and
      2010 was performed. Induction was done by administration of 400 mcg intravaginal
      misoprostol. The correlation between the duration of abortion and maternal,
      fetal, and clinical features were statistically analyzed with multivariate
      regression analysis. RESULTS: One hundred and seventy-five singleton pregnancies
      that met the inclusion criteria were evaluated. The average gestational age at
      the first induction was 18.3 weeks. The mean time interval between the first
      induction and expulsion was 37.2 +/- 21.3 (range 3 to 160) hours. Fetal expulsion
      occurred significantly at a later gestational age and those with a higher blood
      glucose level at admission. However, no correlation could be established between
      the duration of abortion and the number of pregnancies, deliveries, age,
      hemoglobin levels or platelet count. CONCLUSIONS: Misoprostol is safe and
      effective in induction of abortion during second-trimester pregnancies. The
      induction-to-abortion interval is longer in patients with hyperglycemia and
      advanced gestational age. Prospective, randomized studies are necessary to better
      understand the factors influencing the duration of abortion.

PMID- 24283165
TI  - Pre-pregnancy counseling in Lagos: a report on the first 1,000 cases.
AB  - OBJECTIVE: To assess the activity of a pre-pregnancy counseling clinic in terms
      of investigations, counseling, treatment, and subsequent pregnancy outcome.
      MATERIALS AND METHODS: Prenatal diagnosis and therapy were given in a tertiary
      university hospital in Lagos offering referral services for fetal medicine.
      DESIGN: Review of the first 1,000 couples who referred to the centre from various
      centres attended from 1992 to 2007. Main outcome measures were assessed through
      types of referrals, value of diagnostic tests, and subsequent pregnancy outcomes.
      RESULTS: The main types of referral were previous miscarriage (48.2%), previous
      fetal abnormality (10.8%), chronic maternal illness (25.1%), and others (15.9%).
      Routine investigation showed high serological toxoplasmosis, rubella,
      cytomegalovirus, herpes simplex I, herpes simplex II (TORCH) positive antibodies
      carrier rate. Subsequent pregnancy outcome did improve in the chronic maternal
      diseases and previous miscarriage group. CONCLUSIONS: This study illustrates the
      importance of making an accurate assessment of previous problem and current
      health as a means of determining both maternal and fetal risks in a subsequent
      pregnancy.

PMID- 24283166
TI  - A suppository for treating cervical erosion and its preparation method.
AB  - OBJECTIVE: To study a suppository for treating cervical erosion, its preparation
      method, and to observe its therapeutic effect on cervical erosion in animal
      models. METHODS: Twenty rats were divided into five groups: blank control group,
      model group, and three different therapeutic concentration groups. Phenol slurry
      was injected through the vagina to create cervical erosion animal models. After
      seven days of drug treatment, the difference of cervical histopathology was
      observed and compared between different groups. RESULTS: Compared with the
      control group, the model group showed obvious cervical erosion, inflammatory cell
      infiltration, vascular dilatation, and congestion. Among the administration
      group, the high administration group had the least inflammation and cell
      infiltration in the mucous membrane. CONCLUSIONS: There is a significant effect
      of therapeutic drugs in rats with cervical erosion, which is related to the
      concentration of drugs.

PMID- 24283167
TI  - Maternal and umbilical cord oxygen content and acid-base balance in relation to
      general, epidural or subarachnoid anesthesia for term elective cesarean section.
AB  - PURPOSE: To compare maternal and neonatal oxygenation and acid-base status after
      elective cesarean section (CS) under different anesthetic techniques. MATERIALS
      AND METHODS: Three hundred and eighty parturients undergoing elective cesarean
      section were randomly assigned to receive general (GA, n =140), epidural (EA, n =
      117) or subarachnoid anesthesia (SA, n =123). Blood gases, oxygen content, and
      acid-base status parameters were measured in maternal artery and umbilical cord
      vessels. Neonatal Apgar scores were also recorded. RESULTS: Umbilical artery pH,
      HCO3-, and actual base excess (ABE) were significantly higher in the GA compared
      to SA group (p < 0.001, p < 0.05, andp < 0.05, respectively). Umbilical vein ABE
      was lower in the SA compared to GA and EA groups (p < 0.05). Oxygen content in
      maternal artery was higher in the GA and EA groups compared to the SA group (p <
      0.05). Neonatal oxygen content in both cord vessels was higher in the GA group
      compared to EA and SA groups (p < 0.05). Umbilical venous-arterial difference of
      PO2, oxygen content, and Apgar scores did not differ significantly among groups.
      CONCLUSION: Neonatal oxygenation and acid-base status values were better
      preserved when GA was administered for elective CS compared to regional
      modalities. Apgar scores and neonatal outcomes were not affected by the
      anesthetic technique.

PMID- 24283168
TI  - The expression and role of oxidative stress markers in the serum and follicular
      fluid of patients with endometriosis.
AB  - OBJECTIVE: To investigate the expression and role of oxidative stress markers in
      the serum and follicular fluid of patients with endometriosis. MATERIALS AND
      METHODS: A prospective case-control study was conducted in 42 patients who
      underwent in vitro fertilization-embryo transfer (IVF-ET). They were divided into
      Group I: patients with endometriosis (n = 20) and Group II: patients with tubal
      factor infertility (n = 22). All patients underwent a long gonadotropin-releasing
      hormone (GnRH) agonist protocol for pituitary downregulation followed by
      controlled ovarian hyperstimulation. Level of reactive oxygen species (ROS),
      superoxide dismutase (SOD), and vitamin E (VE) were measured by enzyme-linked
      immunosorbent assay (ELISA). The results of IVF-ET between the two groups were
      compared. RESULTS: The ROS levels in both serum and follicular fluid of the study
      group were significantly higher than in the control group. The serum levels of
      SOD and VE in the study group were significantly lower than those in the control
      group, but there was no difference in follicular fluid levels of SOD and VE
      between the two groups. Furthermore, the mature oocyte and fertilization rates in
      the study group were significantly lower than those of the control group.
      However, the levels of ROS, SOD, and VE in serum and follicular fluid were not
      significantly correlated with outcome following IVF-ET. CONCLUSION: Patients with
      endometriosis have increased oxidative stress, as well as lower mature oocyte
      rates and fertilization rates. Nevertheless, there is no evidence that the
      oxidative stress status is directly related to the outcome of IVF treatment.

PMID- 24283169
TI  - Surgical treatment outcomes of serious chronic tubo-ovarian abscess: a single
      center series of 20 cases.
AB  - In recent years, Shimane University Hospital has begun to see patients with
      pelvic inflammatory disease (PID) which has become severe and chronic after
      insufficient conservative treatment in primary or secondary medical care
      facilities. Serious chronic tubo-ovarian abscess (TOA) is complicated by
      intraperitoneal inflammatory adhesions to surrounding organs, so that it is
      difficult to determine the original anatomical position of organs at surgery.
      Forcible synechotomy can result in damage to the adhering organs and insufficient
      drainage after surgery can cause recurrence of inflammation. In order to increase
      the chances for a successful surgical treatment, careful preparation, such as
      preoperative administration of antibiotics and ureteral stent insertion are
      necessary. In addition, the chances for recurrence of inflammation can be
      lessened by thorough intraperitoneal irrigation and insertion of a drainage tube.

PMID- 24283170
TI  - The determination of high-risk pregnancy: the use of antenatal scoring system.
AB  - AIMS: A standardized antenatal scoring system is not available in order to detect
      high-risk pregnancies at primary health care units in Turkey. The authors aimed
      to evaluate the applicability of the "Knox scoring system" in Turkey. MATERIALS
      AND METHODS: One hundred and twenty-nine pregnant women were included in study.
      They were assessed upon admission and then the same women were reassessed at the
      onset of labor by Knox scoring system. RESULTS: The Knox scoring system
      identified 65 pregnant women (50.4%) as high-risk upon admission while 22
      pregnant women (17.1%) as high-risk at the onset of labor. Twelve pregnant women
      (9.3%) (one case of perinatal death and 11 cases of perinatal morbidity) had poor
      perinatal outcomes during the study period. The Knox scoring form administered
      upon admission yielded 58% sensitivity, 50% specificity, and 10% positive
      predictive value, while 91% sensitivity, 90% specificity, and 50% positive
      predictive value at the onset of labor. The diagnostic value of the Knox scoring
      system for determining high-risk pregnancies was not found statistically
      significant regarding admission (ROC value: 0.655; p > 0.05), while statistically
      significant regarding the onset of labor (ROC value: 0.946; p < 0.05).
      CONCLUSIONS: The use of the Knox scoring system for determining high-risk
      pregnancies seems to be effective at the onset of labor.

PMID- 24283171
TI  - Investigation on maternal physiological and psychological factors of
      cheilopalatognathus.
AB  - OBJECTIVE: Case-control study on mothers of cheilopalatognathus children was
      conducted, to investigate the maternal physiological and psychological factors
      for occurrence of cheilopalatognathus. MATERIALS AND METHODS: One hundred ten
      mothers of cheilopalatognathus children who were scheduled for one-stage surgery
      were selected as a research group, and 110 mothers of normal children served as a
      normal control group at the same time. Trait Anxiety Inventory (T-AI), Life
      Events Scale (LES), Trait Coping Style Questionnaire (TCSQ), Type C Behavior
      Scale (CBS), adult Eysenck Personality Questionnaire (EPQ), and homemade general
      questionnaire survey were employed for the investigation. RESULTS: Compared with
      the control group, the scores for negative event tension value, anxiety, and
      depressive factors were higher in the study group (p < 0.05); while the scores
      for positive event tension value, intellect, optimism, and social support factors
      were lower (p < 0.05). Regression analysis found that physiological factors
      included were five: education, changes in body weight during pregnancy, the
      intake amount of milk and beans, and intake of healthcare products, and
      supplementary folic acid taken or not, while the psychological factors included
      were four: positive event stimulation, negative event stimulation, the amount of
      social support, as well as introvert and extrovert personalities. CONCLUSION: The
      study results suggest that pregnant women's physiological and psychological
      factors can cause changes in cheilopalatognathus incidence, which is expected to
      be guidance for healthcare during pregnancy, to prevent the occurrence of
      cheilopalatognathus.

PMID- 24283172
TI  - The effects of hormone therapy on ischemia modified albumin and soluble CD40
      ligand levels in obese surgical menopausal women.
AB  - PURPOSE: To determine the effects of hormone therapy (HT) on ischemia modified
      albumin (IMA) and soluble (s)CD40 ligand in obese surgical menopausal women.
      MATERIALS AND METHODS: A total of 52 obese surgical menopausal women with a body
      mass index (BMI) > 30 kg/m2 were admitted to the study. Twenty-seven women
      received estradiol hemihydrate two mg and 25 did not receive any menopausal
      therapy. At baseline and after three and six months of treatment, IMA and sCD40
      ligand levels were measured. RESULTS: There were no significant differences among
      the groups for any variables at baseline. No difference in change in the serum
      sCD40L levels was found in obese surgical menopausal women after three and six
      months of HT. Serum IMA levels were statistically lowered in obese women with HT
      after six months of treatment. CONCLUSION: HT may have a beneficial reduction in
      IMA levels in obese surgical menopausal women.

PMID- 24283173
TI  - Reference charts and equations of fetal biometry for normal singleton pregnant
      women in Shaanxi, China.
AB  - OBJECTIVE: To construct reference charts and equations of fetal biometry for
      singleton pregnant women in Shaanxi, China. MATERIALS AND METHODS: This was a
      cross-sectional study involving 6,832 singleton pregnant women. One set of fetal
      ultrasonographic measurement data between the 16th to 41st gestational weeks (GW)
      was randomly selected from each pregnant woman, and biparietal diameter (BPD),
      abdominal circumference (AC), and femur length (FL) were recorded. Mean and
      standard deviation (SD) of BPD, AC, and FL were fitted by polynomial. Centile =
      Mean + Z(alpha) x SD was used to calculate centiles. Differences in the 50th
      centile of BPD, AC, and FL between Hong Kong, Korean, Italian and Shaanxi fetuses
      were compared. RESULTS: Mean of BPD, AC, and FL were well-fitted by quadratic
      polynomial, SD of BPD, AC and FL were fitted by linear regression. Equations for
      estimating mean and SD for BPD, AC, and FL from GW were obtained. Centiles for
      BPD,AC, and FL were calculated. From the 21st GW, the differences in BPD,AC, and
      FL between Hong Kong, Korean, Italian, and Shaanxi fetuses became larger.
      CONCLUSION: Fetal biometry reference charts and equations for estimating fetal
      size and GW could be used in obstetrics practice and research in Shaanxi, China.

PMID- 24283174
TI  - Association between periodontal disease and adverse pregnancy outcomes in a
      cohort of pregnant women in Jordan.
AB  - BACKGROUND: The relationship between periodontal disease (PD) and adverse
      pregnancy outcomes remain unclear. The authors' objective was to assess the risk
      of adverse pregnancy outcomes in Jordanian women with periodontal disease
      compared to those without. MATERIALS AND METHODS: Between April 2009 and June
      2010, 277 pregnant women with no systemic diseases at gestational age < 20 weeks
      were enrolled in the study. Dental and oral health examination was performed at
      enrollment after demographic, medical, and obstetrical information were recorded.
      Pregnancy outcomes were obtained by phone contact and review of medical records.
      RESULTS: The incidence of periodontal disease in the pregnant women enrolled was
      31%. Women with PD were at higher risk for developing preeclampsia (PE), preterm
      birth (PB), and low birth weight (LBW). The rate of PE in women with PD was 18.6%
      compared to 7.3% in the control group (p = 0.005) (OR = 2.7, 95% CI: 1.2, 6.0).
      The OR for PB was (4.4, 95% CI: 1.7, 11.7) and for LBW was (3.5, 95% CI: 1.6,
      7.5). CONCLUSIONS: PD is associated with increased risk of PE, PB, and LBW in
      healthy Jordanian women.

PMID- 24283175
TI  - Anesthesia management for open fetal intrauterine surgery.
AB  - OBJECTIVE: Open fetal surgery is usually performed during the second trimester in
      a fetus suffering from severe congenital diseases, thus enabling the pregnancy to
      continue until delivery. MATERIALS AND METHODS: The key of this treatment is to
      promote uterine relaxation enough to maintain both maternal and fetal circulation
      stable and once surgery is completed, to offer a perfect analgesic to avoid the
      contractions due to pain, and finally to reduce preterm delivery. RESULTS:
      Successful anesthesia is fundamental to this surgery. CONCLUSION: The authors
      have performed three cases under inhalation anesthesia combined with successful
      epidural anesthesia.

PMID- 24283176
TI  - Prevalence of genital warts in reproductive-aged Turkish women presenting at
      gynecology outpatient clinics for any reason.
AB  - The objective of this multicenter descriptive study was to calculate the
      frequency of genital warts among Turkish women aged 15-49 years, who visited
      outpatient gynecology clinics for a variety of reasons. The study was conducted
      in February 2011 to collect data for a minimum of 154 patients at each center,
      and the total sample size reached 2,967 women (95.1% completion rate). Oral
      informed consents were obtained. A questionnaire including data on socio
      demographic characteristics and reasons for admission was administered, and a
      pelvic examination was performed. The overall point prevalence was 35% (95% CI =
      3.1%-4.0%), correcting for sampling design, with the highest rates observed in
      the 15 to 19-year-old group. The odds of having a genital wart was 1.82 times
      (95% CI = 0.99-3.33) higher among non-pregnant participants than in pregnant
      women (p = 0.051). The overall point prevalence of genital warts among
      reproductive-aged women attending gynecology outpatient clinics for any reason in
      Turkey was 35%.

PMID- 24283177
TI  - Sperm pooling and intrauterine tuboperitoneal insemination for mild male factor
      infertility.
AB  - PURPOSE OF INVESTIGATION: To evaluate the efficacy of sperm pooling in the
      treatment of male infertility with the use of intrauterine tuboperitoneal
      insemination (IUTPI). MATERIALS AND METHODS: A total of 169 cycles of IUTPI were
      performed in 69 couples with mild male factor infertility. Pooled semen samples
      were used in 115 cycles (Group A), whereas a single sample was used in 54 (Group
      B). The same mild ovarian stimulation protocols were used in all cycles. RESULTS:
      The mean inseminate motile count (IMC), following sperm pooling was 6.63 x 10(6)
      in Group A and 3.74 x 10(6) in Group B (p = 0.0001) with a single semen sample.
      In total, 33 clinical pregnancies were achieved; 28 (24%) in Group A and five
      (9%) in Group B (p = 0.036). CONCLUSIONS: The results of this study indicate that
      sperm pooling may prove a useful technique in the treatment of mild male
      infertility when combined with IUTPI.

PMID- 24283178
TI  - Is laparoscopic surgery safe in patients with an elevated shock index due to
      ruptured ectopic pregnancy?
AB  - PURPOSE: To evaluate the effectiveness of laparoscopic surgery in patients with
      elevated shock index (SI), which is a unique determinant of acute hemorrhage.
      MATERIALS AND METHODS: A retrospective chart review of all patients treated for
      ectopic pregnancy (EP) in the present gynaecology department between January 2007
      and March 2011 was performed. For each measurement of heart rate (HR) and
      systolic blood pressure (SBP), a SI was calculated by dividing HR by SBP (normal,
      0.5 - 0.7). RESULTS: One hundred sixty patients were selected as SI above 0.7.
      There were 111 (69.4%) patients in the laparotomy group and 49 (30.6%) patients
      in the laparoscopy group. The postoperative hemoglobin (Hb) level was 8.46 +/-
      1.56 (g/dl) in the laparotomy group and 9.37 +/- 1.52 (g/dl) in the laparoscopy
      group, with lower postoperative levels in the laparotomy group. The mean duration
      of postoperative hospital stay was 2.37 +/- 0.74 days in the laparotomy group and
      2 +/- 0.84 days in the laparoscopy group. CONCLUSION: The availability of
      suitable operative equipment, nursing teams, and advanced laparoscopic skills,
      all justify operative laparoscopy for the surgical treatment of EP in women with
      elevated SI.

PMID- 24283179
TI  - A comparison of the effect of levonorgestrel IUD with oral medroxyprogesterone
      acetate on abnormal uterine bleeding with simple endometrial hyperplasia and
      fertility preservation.
AB  - OBJECTIVE: Endometrial hyperplasia is clinically important, because it can lead
      to abnormal uterine bleeding (AUB) which itself can precede endometrial cancer.
      Endometrial carcinoma is the most common malignancy of the female genital tract,
      occurring in about 75%-85% younger, perimenopausal women as endometrial
      hyperplasia. The treatment is hysterectomy or hormone therapy with progesterone.
      The aim of this study was, therefore, to compare the effect of levonorgestrel
      intrauterine device (LNG-IUD) with medroxyprogesterone acetate (MPA) on simple
      endometrial hyperplasia for fertility preservation. MATERIALS AND METHODS: Forty
      women in reproductive age (22-47 years) with AUB with endometrial biopsies
      confirming simple hyperplasia, were enrolled in this study and then randomly
      divided into two groups. All patients presented with designed special checklist
      which was filled with satisfaction. Complete history and physical examination
      especially blood pressure (BP), body mass index (BMI), breast examination,
      bimanual vaginal examination, and transvaginal sonography (to measure the
      thickness of endometrial and exclude the other pathologic lesions) were
      performed. In the first group, treatment was performed with MPA (20 mg/daily) for
      ten days and in other group with LNG-IUD was prescribed. After three months,
      transvaginal sonography and biopsy of endometrium were done. The status of AUB
      and side-effects of two methods,along with the rate of satisfactory were
      evaluated. RESULT: The findings showed the significant differences in the
      treatment of simple hyperplasia between two groups (LNG-IUD group vs. MPA group)
      (p < 0.047). Recovery of AUB in the group LNG was enhanced (p < 0.047).
      Endometrial thickness was reduced in both groups (p < 0.001), but further
      reduction in LNG group was seen. Also, LNG was tolerated more than MPA. Side
      effects of MPA were more and reached significance (p < 0.003). The rate of
      satisfaction with LNG was higher than MPA and reached significance (p < 0.048).
      CONCLUSION: The results of this study show that LNG-IUD is more effective than
      MPA in treatment of simple endometrial hyperplasia and can be helpful in young
      women who want to preserve their fertilities.

PMID- 24283180
TI  - CD34 expression of chorionic villous in pre-eclamptic placenta: an
      immunohistochemical and ultrastructural study.
AB  - In this study, pre-eclampsia, proteinuria, and edema associated with hypertension
      in pregnancy were assessed at the Dicle University School of Medicine Department
      of Obstetrics and Gynecology Clinic. One group included 20 pre-eclamptic pregnant
      women with gestational age 20-35 weeks of pregnancy and the same in the control
      group that included; however, 20 normotensive pregnant women. Histochemistry,
      immunohistochemistry, and electron microscopy techniques were used.
      Histopathological examination of syncytial nodes and stromal cells were observed
      in the increase in hyperplasia and hyalinization. The evaluation
      immunohistochemical of chorionic villi, placenta, and hematopoietic stem cell
      markers showed a positive reaction with CD34. Ultrastructural examination showed
      endoplasmic reticulum dilatation, degeneration of mitochondria in endothelial
      cells, and capillary vessel edema.

PMID- 24283181
TI  - Association between mean platelet volume and different phases of menstrual cycle
      in primary dysmenorrhea.
AB  - PURPOSE: Blood cells play a major role in homeostasis and inflammation. Primary
      dysmenorrhea (PD) involves the production of prostaglandins and leukotrienes,
      which cause inflammation in uterine tissue. Aim of this study was to investigate
      whether there is a relation between complete blood count parameters and PD during
      the menstrual cycle. MATERIALS AND METHODS: The study included 41 cases diagnosed
      as primary dysmenorrhea (mean age, 23.02 +/- 3.43 years) and 40 individuals who
      control subject (mean age, 23.76 +/- 3.13 years). Hematologic parameters were
      measured on menstrual phase (day 1-4), follicular phase (day 9-12), and luteal
      phase (day 21-23) during menstrual cycle. RESULTS: There were no statistically
      differences between hematological parameters of two groups except for mean
      platelet volume (MPV). MPV of PD and control groups at each phase of menstrual
      cycle were 7.71 vs 8.61 (p = 0.01); 7.66 vs 8.56 (p = 0.005); 7.75 vs 8.53 (p =
      0.01), respectively. CONCLUSION: PD is associated with decreased MPV and
      platelets may be involved in the inflammatory process of PD.

PMID- 24283182
TI  - Mild increases in serum FSH in late follicular phase increases the risk of the
      luteinized unruptured follicle: case report.
AB  - PURPOSE: To find a case that will support the concept that mild elevation of
      serum follicle stimulating hormone (FSH) levels in late follicular phase may
      interfere with the release of the oocyte from the follicle. MATERIALS AND
      METHODS: Oocyte release was determined in a woman in a complete natural cycle vs
      cycles where a boost of very low dose FSH was given, human chorionic gonadotropin
      (hCG) 10,000 units or leuprolide acetate 1 mg every 12 hours x two doses was
      given in FSH stimulated cycles. RESULTS: Oocyte release occurred in all natural
      cycles vs none of the mildly stimulated cycles. CONCLUSIONS: Mild changes in the
      FSH level in the late luteal phase may affect the production of certain FSH
      dependent factors needed to release the oocyte.

PMID- 24283183
TI  - An autopsy case of acute aortic dissection during postpartum period.
AB  - BACKGROUND: Aortic dissection in young women without Marfan disease is related in
      most instances to pregnancy. This is a potentially catastrophic occurrence. CASE:
      An autopsy case of acute aortic dissection type B (Stanford classification),
      clinically undiagnosed during late puerperium period in a young woman with no
      discernible risk factors (e.g. family history and signs of connective tissue
      diseases) is presented. Autopsy with ancillary investigations revealed that
      knowledge of this albeit relatively rare complication of postpartum may assist
      the clinician in earlier diagnosis and referral of patients for surgical
      treatment. CONCLUSION: This case is presented to raise awareness and review the
      literature for the critical care of postpartum patients.

PMID- 24283184
TI  - Immature malignant sacrococcygeal teratoma: case report and review of the
      literature.
AB  - Immature malignant sacrococcygeal teratoma (SCT) is a rare tumor, deriving from
      the three germinal layers and is found in the sacrococcygeal region. It is the
      most frequent site of teratomas in the fetus. A nut-brown, solid tumor with
      cystic areas with a ten-cm diameter is reported in the sacrococcygeal region of a
      female fetus of 23 weeks and with a weight of 308 g. The ultrasound and pathology
      evaluations revealed characteristics of an immature malignant SCT. The incidence
      of this tumor type is one in 35,000 to 40,000 live births and females are four
      times more likely to be affected than males. Sacrococcygeal and cervical
      teratomas can be diagnosed by prenatal ultrasound and magnetic resonance imaging
      (MRI). Teratomas are considered an interesting field for research.

PMID- 24283185
TI  - Laparoscopic surgery for ectopic pregnancy within a cesarean scar.
AB  - BACKGROUND: Ectopic pregnancy in a previous cesarean section scar is rarely
      reported, and is very difficult to manage. There are only 12 cases to date that
      have been successfully managed under laparoscopy. CASES: Two females were
      admitted to this Hospital and were suspected to suffer from ectopic pregnancy
      from a previous cesarean section scar under the impression of Doppler ultrasound.
      Conservative regimen was first applied to one patient but failed to demonstrate
      enough efficacy. The beta-human chorionic gonadotropin (beta-HCG) of the other
      patient was extremely high, therefore conservative treatment was not considered.
      Then laparoscopic surgery was performed for the two patients and not only
      confirmed the diagnosis, but also successfully removed the ectopic gestational
      products. Surgery under laparoscopy was uneventful. Total surgical time was 80
      minutes, blood loss was only about 100 ml, and blood transfusion was not
      necessary. CONCLUSION: It seems that for a skilled surgeon, laparoscopy may be a
      sound and reasonable technique to diagnose and resect ectopic pregnancy within a
      cesarean scar.

PMID- 24283186
TI  - Heterotopic pregnancy diagnosed before the onset of severe symptoms: case report.
AB  - BACKGROUND: A heterotopic pregnancy (HP) is an extremely rare disease that
      represents the simultaneous occurrence of two or more implantation sites in the
      uterus and extrauterus. Early diagnosis of HP is difficult because of the
      presence of an intrauterine pregnancy (IUP). In most cases, a precise diagnosis
      was made after symptoms develop through the rupture or bleeding of the ectopic
      pregnancy (EP). The authors present a case that was successfully diagnosed as an
      undemonstrative HP. CASE: A 24-year-old multiparous woman became pregnant after
      taking clomiphene citrate. At ten weeks of pregnancy, an ultrasonography revealed
      gestational sacs containing fetuses in the uterus and the right adnexal region,
      respectively. The patient was diagnosed as having a HP and an emergency right
      tubal resectomy was performed. The IUP progressed normally and the fetus was
      delivered at 37 weeks of pregnancy. DISCUSSION: Even if a gestational sac can be
      confirmed in the uterus, a careful ultrasonographic examination should always be
      considered to determine the presence of a concurrent extrauterine pregnancy.

PMID- 24283187
TI  - Second-trimester miscarriage and umbilical cord knot. Case report and review of
      the literature.
AB  - PURPOSE OF INVESTIGATION: The present study presents a case with an umbilical
      cord knot along with extensive literature review. MATERIALS AND METHODS:
      Presentation of a rare case of second-trimester abortion which was attributed to
      a tight umbilical cord knot. Furthermore the authors reviewed the literature from
      1952 to 2012 in order to compare impact of knots on intrapartum and perinatal
      outcomes. RESULTS: Four large retrospective studies assessed several predisposing
      factors. Long umbilical cords, male embryos, and multiparity were correlated with
      knots in three of these studies. Data regarding perinatal effects of true knots
      from three studies were summarized and compared. CONCLUSION: Umbilical cord true
      knots during the second trimester could be a very rare cause of abortion. The
      presence of knots during the third trimester and labor do not seem to be
      associated with increased perinatal and intrapartum morbidity and mortality,
      although there is still some controversy in the literature on this topic.

PMID- 24283188
TI  - Urethral sex in a woman with previously undiagnosed Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - PURPOSE: To report a case of urethral sex in a woman with previously undiagnosed
      Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. MATERIALS AND METHODS: A 32-year
      old woman presented with severe pain, dysuria, and mild hematuria after each
      intercourse. Secondary sexual characteristics were normal. Vaginal and rectal
      examinations revealed an absent vagina and uterus. Further investigations showed
      a normal hormonal profile, a 46 XX karyotype, and a normal intravenous
      pyelography. Pelvic ultrasonography and magnetic resonance imaging (MRI)
      confirmed the absence of a uterus and the presence of bilateral ovaries. RESULTS:
      A diagnosis of MRKH syndrome was made and the patient underwent a modified
      Vecchietti operation for the creation of a new vagina. The urethral meatus was
      noticeably dilated. Postoperatively, the vaginal length was six to seven cm. Long
      term follow-up revealed that she was able to have normal and satisfactory vaginal
      intercourse without any problems. CONCLUSION: Urethral intercourse is documented
      here for the first time in a case of misdiagnosed MRKH syndrome.

PMID- 24283189
TI  - Antepartum embolization in management of labor induction in placenta previa.
AB  - The authors present a case of a 29-year-old woman, gravid 2 para 1, who
      experienced complete placenta previa and underwent vaginal delivery, after
      performing antepartum uterine artery embolization and rivanol amniotic injection
      due to contraindication of obstetric surgery. In this case, treatment was
      successful despite thromboembolism. Hypercoagulability in pregnancy needs to be
      addressed.

PMID- 24283190
TI  - Simultaneous dermoid cyst and endometriosis in the same ovary: a case report.
AB  - The authors present a case of a 33-year-old infertile woman with coincidental
      dermoid cyst and ovarian endometriosis in the same ovary. She was admitted to the
      Clinic because of cystic tumor of the left adnexa. Transvaginal ultrasound (TVUS)
      examination found a bilocular tumor of complex structure on the left ovary. Video
      laparoscopy was also performed. On the left ovary, two adjacent cystic formations
      were found. Laparoscopic ovarian cystectomy was performed and a surgical specimen
      was sent for histopathologic analysis. The diagnosis was a dermoid cyst and
      ovarian endometriosis. Without complications, the patient was released from the
      hospital. The patient was treated with an analogue of gonadotropin releasing
      hormone (GnRH) for three months as a preparation for in vitro fertilization
      (IVF).

PMID- 24283191
TI  - Congenital disorder of true cyclopia with polydactylia: case report and review of
      the literature.
AB  - Cyclopia is a rare type of holoprosencephaly and a congenital disorder
      characterized by the failure of the embryonic forebrain to properly divide the
      orbits of the eye into two cavities (the embryonic forebrain is normally
      responsible for inducing the development of the orbits). As a result a birth
      defect in which there is only one eye is developed. This eye is centrally placed
      in the area normally occupied by the root of the nose. As a rule, there is a
      missing nose or a non-functioning nose in the form of a proboscis (a tubular
      appendage) located above the central eye. In this report the macroscopic,
      radiographic, and immunohistochemical findings of a case of true cyclopia in a
      female fetus are described. Cyclopia is a lethal condition that is associated
      with dramatic symmetric deformities of the nose, skull, orbits, and brain.

PMID- 24283192
TI  - Gene position more strongly influences cell-free protein expression from operons
      than T7 transcriptional promoter strength.
AB  - The cell-free transcription-translation of multiple proteins typically exploits
      genes placed behind strong transcriptional promoters that reside on separate
      pieces of DNA so that protein levels can be easily controlled by changing DNA
      template concentration. However, such systems are not amenable to the
      construction of artificial cells with a synthetic genome. Herein, we evaluated
      the activity of a series of T7 transcriptional promoters by monitoring the
      fluorescence arising from a genetically encoded Spinach aptamer. Subsequently the
      influences of transcriptional promoter strength on fluorescent protein synthesis
      from one, two, and three gene operons were assessed. It was found that
      transcriptional promoter strength was more effective at controlling RNA synthesis
      than protein synthesis in vitro with the PURE system. Conversely, the gene
      position within the operon strongly influenced protein synthesis but not RNA
      synthesis. 

PMID- 24283193
TI  - Crystal structure of the interferon gamma receptor alpha chain from chicken
      reveals an undetected extra helix compared with the human counterparts.
AB  - Interferon gamma (IFN-gamma) is an important cytokine that induces antiviral,
      antiproliferative, and immunomodulatory effects on target cells, and is also
      crucial in the early defense against intracellular parasites, such as Listeria
      monocytogenes and Toxoplasma gondii. The biological activity of IFN-gamma relies
      upon the formation of a complex with its 2 receptors, the interferon gamma alpha
      chain (IFNGR1) and beta chain (IFNGR2), which are type II cytokine receptors.
      Structural models of ligand-receptor interaction and complex structure of chicken
      IFNs with their receptors have remained elusive. Here we report the first
      structure of Gallus gallus (chicken) IFNGR1 (chIFNGR1) at 2.0 A by molecule
      replacement according to the structure of selenomethionine substituted chIFNGR1.
      The structural comparison reveals its structural similarities with other class II
      cytokine receptors, despite divergent primary sequences. We further investigate
      the ligand-receptor interaction properties of chicken IFN-gamma (chIFN-gamma) and
      chIFNGR1 using size-exclusion chromatography and surface plasmon resonance
      techniques. These data aid in the understanding of the interaction of chicken
      (avian) IFN-gamma with its receptors and its signal transduction. 

PMID- 24283194
TI  - Molecularly doped metals.
AB  - The many millions of organic, inorganic, and bioorganic molecules represent a
      very rich library of chemical, biological, and physical properties that do not
      show up among the approximately 100 metals. The ability to imbue metals with any
      of these molecular properties would open up tremendous potential for the
      development of new materials. In addition to their traditional features and their
      traditional applications, metals would have new traits, which would merge their
      classical virtues such as conductivity and catalytic activity with the diverse
      properties of these molecules. In this Account, we describe a new materials
      methodology, which enables, for the first time, the incorporation and entrapment
      of small organic molecules, polymers, and biomolecules within metals. These new
      materials are denoted dopant@metal. The creation of dopant@metal yields new
      properties that are more than or different from the sum of the individual
      properties of the two components. So far we have developed methods for the doping
      of silver, copper, gold, iron, palladium, platinum, and some of their alloys, as
      well as Hg-Ag amalgams. We have successfully altered classical metal properties
      (such as conductivity), induced unorthodox properties (such as rendering a metal
      acidic or basic), used metals as heterogeneous matrices for homogeneous
      catalysts, and formed new metallic catalysts such as metals doped with
      organometallic complexes. In addition, we have created materials that straddle
      the border between polymers and metals, we have entrapped enzymes to form
      bioactive metals, we have induced chirality within metals, we have made corrosion
      resistant iron, we formed efficient biocidal materials, and we demonstrated a new
      concept for batteries. We have developed a variety of methods for synthesizing
      dopant@metals including aqueous homogeneous and heterogeneous reductions of the
      metal cations, reductions in DMF, electrochemical entrapments, thermal
      decompositions of zerovalent metal carbonyls, and dissolution during amalgam
      formation. The structures of these dopant@metal materials indicate that metals
      entrap the organic molecules within their agglomerated nanocrystals. As a result,
      these materials are porous, making the dopant accessible for chemical reactions,
      in particular for catalysis. We have prepared these materials in a variety of
      forms, including powder, granules, pressed discs, thin films, thick films, sub
      micrometer particles, and nanometric particles decorating ceramic nanofibers.
      Entrapment and adsorption are very different processes. If entrapped, water
      soluble molecules cannot be extracted, but the same molecules, if adsorbed, are
      easily washed away. Likewise, most of the special properties that we have
      observed, such as major improvements or changes in catalytic activity, completely
      different thermal gravimetric analysis behavior, and more, are observed only in
      the entrapped cases. 

PMID- 24283195
TI  - Cigarette smoke induces distinct histone modifications in lung cells:
      implications for the pathogenesis of COPD and lung cancer.
AB  - Cigarette smoke (CS)-mediated oxidative stress induces several signaling
      cascades, including kinases, which results in chromatin modifications (histone
      acetylation/deacetylation and histone methylation/demethylation). We have
      previously reported that CS induces chromatin remodeling in pro-inflammatory gene
      promoters; however, the underlying site-specific histone marks formed in histones
      H3 and H4 during CS exposure in lungs in vivo and in lung cells in vitro, which
      can either drive gene expression or repression, are not known. We hypothesize
      that CS exposure in mouse and human bronchial epithelial cells (H292) can cause
      site-specific posttranslational histone modifications (PTMs) that may play an
      important role in the pathogenesis of CS-induced chronic lung diseases. We used a
      bottom-up mass spectrometry approach to identify some potentially novel histone
      marks, including acetylation, monomethylation, and dimethylation, in specific
      lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells.
      We found that CS-induced distinct posttranslational histone modification patterns
      in histone H3 and histone H4 in lung cells, which may be considered as usable
      biomarkers for CS-induced chronic lung diseases. These identified histone marks
      (histone H3 and histone H4) may play an important role in the epigenetic state
      during the pathogenesis of smoking-induced chronic lung diseases, such as chronic
      obstructive pulmonary disease and lung cancer. 

PMID- 24283196
TI  - Insights into atomic-level interaction between mefenamic acid and eudragit EPO in
      a supersaturated solution by high-resolution magic-angle spinning NMR
      spectroscopy.
AB  - The intermolecular interaction between mefenamic acid (MFA), a poorly water
      soluble nonsteroidal anti-inflammatory drug, and Eudragit EPO (EPO), a water
      soluble polymer, is investigated in their supersaturated solution using high
      resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR)
      spectroscopy. The stable supersaturated solution with a high MFA concentration of
      3.0 mg/mL is prepared by dispersing the amorphous solid dispersion into a d
      acetate buffer at pH 5.5 and 37  degrees C. By virtue of MAS at 2.7 kHz, the
      extremely broad and unresolved (1)H resonances of MFA in one-dimensional (1)H NMR
      spectrum of the supersaturated solution are well-resolved, thus enabling the
      complete assignment of MFA (1)H resonances in the aqueous solution. Two
      dimensional (2D) (1)H/(1)H nuclear Overhauser effect spectroscopy (NOESY) and
      radio frequency-driven recoupling (RFDR) under MAS conditions reveal the
      interaction of MFA with EPO in the supersaturated solution at an atomic level.
      The strong cross-correlations observed in the 2D (1)H/(1)H NMR spectra indicate a
      hydrophobic interaction between the aromatic group of MFA and the backbone of
      EPO. Furthermore, the aminoalkyl group in the side chain of EPO forms a
      hydrophilic interaction, which can be either electrostatic or hydrogen bonding,
      with the carboxyl group of MFA. We believe these hydrophobic and hydrophilic
      interactions between MFA and EPO molecules play a key role in the formation of
      this extremely stable supersaturated solution. In addition, 2D (1)H/(1)H RFDR
      demonstrates that the molecular MFA-EPO interaction is quite flexible and
      dynamic. 

PMID- 24283197
TI  - Unexpected abrupt increase in left ventricular assist device thrombosis.
AB  - BACKGROUND: We observed an apparent increase in the rate of device thrombosis
      among patients who received the HeartMate II left ventricular assist device, as
      compared with preapproval clinical-trial results and initial experience. We
      investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase
      (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and
      outcomes of different management strategies in a multi-institutional study.
      METHODS: We obtained data from 837 patients at three institutions, where 895
      devices were implanted from 2004 through mid-2013; the mean (+/-SD) age of the
      patients was 55+/-14 years. The primary end point was confirmed pump thrombosis.
      Secondary end points were confirmed and suspected thrombosis, longitudinal LDH
      levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump
      thromboses were confirmed in 66 patients; an additional 36 thromboses in unique
      devices were suspected. Starting in approximately March 2011, the occurrence of
      confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95%
      confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1,
      2013. Before March 1, 2011, the median time from implantation to thrombosis was
      18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months
      (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months
      after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH
      levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within
      the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11
      patients (1 patient died 31 days after transplantation) and by pump replacement
      in 21, with mortality equivalent to that among patients without thrombosis; among
      40 thromboses in 40 patients who did not undergo transplantation or pump
      replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing
      6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related
      to the use of the HeartMate II has been increasing at our centers and is
      associated with substantial morbidity and mortality.

PMID- 24283198
TI  - New insights into the dementia epidemic.

PMID- 24283199
TI  - A pragmatic view of the new cholesterol treatment guidelines.

PMID- 24283200
TI  - Musculoskeletal disorders amongst Greek endodontists: a national questionnaire
      survey.
AB  - AIM: To investigate amongst Greek endodontists the prevalence and characteristics
      of musculoskeletal disorders (MSDs) in the past 12 months, the treatment
      followed, their postures during practice and the adoption of ergonomic standards.
      METHODOLOGY: One hundred and forty-seven endodontists met the inclusion criteria
      and were invited to participate in the survey. Participants were asked for
      personal/professional data, prevalence, characteristics and treatment for MDSs in
      the past 12 months. Endodontists' postures during practice as well as ergonomic
      factors were also recorded. Data were analysed using chi-square test, independent
      samples t-test and logistic regression. The level of significance was set at P =
      0.05. RESULTS: The response rate was 84%. MSDs were reported by 61% of the
      participants. Of them, 69% reported pain to more than one body part. The
      prevalence of disorders was highest in the lower back (30%) and neck (30%).
      Medical care was applied in 53% of the disorders. A sitting position was always
      used by 83% of endodontists. Awkward postures during practice (OR:4.561, 95%
      CI:1.341-15.512), regular stretching exercises (OR:0.032, 95% CI:0.010-0.110) and
      number of patients day(-1) (OR:3.524, 95% CI:1.686-18.100) were significant
      predictors for MSDs. Properly adjusted stools, sufficient lighting and space in
      the operating room were reported by 71%, 96% and 93% of participants,
      respectively. CONCLUSIONS: A high percentage of endodontists reported MSDs.
      Adoption of correct/neutral postures, regular performance of stretching exercises
      and reduced number of patients/day were associated with a low prevalence of
      disorders. The majority of endodontists had adopted ergonomic
      innovations/standards to control disorders.

PMID- 24283201
TI  - Evaluation of WO2013136076: two crystalline forms of the phosphatidylinositol 3
      kinase-delta inhibitor RV-1729.
AB  - This application claims two crystalline forms and inhaled formulations of a the
      selective phosphatidylinositol 3-kinase-delta inhibitor (PI3Kdelta) inhibitor 6
      (2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-(2
      chlorobenzyl)-4-oxo-3,4-dihydroquinazolin-5-yl)-N, N-bis(2-methoxyethyl)hex-5
      ynamide. These formulations are claimed to be useful in the treatment of
      respiratory diseases including asthma and chronic obstructive pulmonary disease. 

PMID- 24283202
TI  - Interim analysis of safety and efficacy of ruxolitinib in patients with
      myelofibrosis and low platelet counts.
AB  - BACKGROUND: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated
      improvements in spleen volume, symptoms, and survival over placebo and best
      available therapy in intermediate-2 or high-risk myelofibrosis patients with
      baseline platelet counts >=100 * 109/L in phase III studies. The most common
      adverse events were dose-dependent anemia and thrombocytopenia, which were
      anticipated because thrombopoietin and erythropoietin signal through JAK2. These
      events were manageable, rarely leading to treatment discontinuation. Because
      approximately one-quarter of MF patients have platelet counts <100 * 109/L
      consequent to their disease, ruxolitinib was evaluated in this subset of patients
      using lower initial doses. Interim results of a phase II study of ruxolitinib in
      myelofibrosis patients with baseline platelet counts of 50-100 * 109/L are
      reported. METHODS: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID),
      and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if
      platelet counts remained adequate. Additional dosage increases required evidence
      of suboptimal efficacy. Assessments included measurement of spleen volume by MRI,
      MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]),
      Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and
      safety/tolerability. RESULTS: By week 24, 62% of patients achieved stable doses
      >=10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%,
      respectively. Thrombocytopenia necessitating dose reductions and dose
      interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in
      patients with baseline platelet counts <=75 * 109/L. Seven patients experienced
      platelet count increases >=15 * 109/L. Mean hemoglobin levels remained stable
      over the treatment period. Two patients discontinued for adverse events: 1 for
      grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre
      existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. CONCLUSIONS:
      Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg
      BID may be appropriate in myelofibrosis patients with low platelet counts.

PMID- 24283203
TI  - Containing the accidental laboratory escape of potential pandemic influenza
      viruses.
AB  - BACKGROUND: The recent work on the modified H5N1 has stirred an intense debate on
      the risk associated with the accidental release from biosafety laboratory of
      potential pandemic pathogens. Here, we assess the risk that the accidental escape
      of a novel transmissible influenza strain would not be contained in the local
      community. METHODS: We develop here a detailed agent-based model that
      specifically considers laboratory workers and their contacts in microsimulations
      of the epidemic onset. We consider the following non-pharmaceutical
      interventions: isolation of the laboratory, laboratory workers' household
      quarantine, contact tracing of cases and subsequent household quarantine of
      identified secondary cases, and school and workplace closure both preventive and
      reactive. RESULTS: Model simulations suggest that there is a non-negligible
      probability (5% to 15%), strongly dependent on reproduction number and
      probability of developing clinical symptoms, that the escape event is not
      detected at all. We find that the containment depends on the timely
      implementation of non-pharmaceutical interventions and contact tracing and it may
      be effective (>90% probability per event) only for pathogens with moderate
      transmissibility (reproductive number no larger than R0 = 1.5). Containment
      depends on population density and structure as well, with a probability of giving
      rise to a global event that is three to five times lower in rural areas.
      CONCLUSIONS: Results suggest that controllability of escape events is not
      guaranteed and, given the rapid increase of biosafety laboratories worldwide,
      this poses a serious threat to human health. Our findings may be relevant to
      policy makers when designing adequate preparedness plans and may have important
      implications for determining the location of new biosafety laboratories
      worldwide.

PMID- 24283204
TI  - Cigarette smoking and alcohol use as predictors of HIV testing in the United
      States: results from the 2010 National Health Interview Survey.
AB  - We examined the association between HIV risk perception and HIV testing among
      cigarette smokers, alcohol users, dual consumers of cigarette and alcohol, and
      abstainers. Data were analyzed from the 2010 National Health Interview Survey of
      the full sample of 22,946 and separately for 1547 African Americans. Multivariate
      logistic regression analysis revealed that alcohol users and dual consumers were
      significantly more likely to perceive themselves to be at risk of acquiring HIV.
      Cigarette smokers and alcohol users who considered themselves to be at risk for
      HIV and dual consumers who reported no perceived HIV risk were more likely to
      have been tested for HIV than abstainers who perceived no risk of acquiring HIV.
      Among African Americans, dual consumers and cigarette smokers only who perceived
      themselves at risk for HIV were more likely to have been tested for HIV than
      abstainers who perceived no risk of HIV infection. This study demonstrated that
      among the full sample and African Americans, cigarette smoking and alcohol use
      were significantly associated with HIV testing regardless of HIV risk
      perceptions.

PMID- 24283205
TI  - Actual immunization coverage throughout Europe: are existing data sufficient?
AB  - Assessing vaccine coverage is an essential component of vaccine programme
      monitoring and evaluation. Vaccine coverage data are available in EU/EEA
      countries at both national and subnational levels and are used for programmatic
      purposes at any level. European-wide data collection is performed by WHO through
      the Centralized Information System for Infectious Diseases, as part of the global
      data collection jointly conducted with UNICEF. Data quality and comparability are
      still challenging at an international level. According to available information,
      vaccination registries are available in 11 countries in the EU/EEA, but only in
      five countries do they have national coverage. In 2012 ECDC, through the VENICE
      II network, started the European Vaccination Coverage Collection System (EVACO
      project), with the final aim of improving the quality of vaccine coverage data at
      EU level, by defining and implementing standards. 

PMID- 24283206
TI  - Peripheral blood absolute lymphocyte/monocyte ratio as a useful prognostic factor
      in diffuse large B-cell lymphoma in the rituximab era.
AB  - OBJECTIVES: The tumor microenvironment, including tumor-infiltrating lymphocytes
      and myeloid-derived cells, is an important factor in the pathogenesis and
      clinical behavior of malignant lymphoma. However, the prognostic significance of
      peripheral lymphocytes and monocytes in lymphoma remains unclear. METHODS: We
      evaluated the prognostic impact of the absolute lymphocyte count (ALC), absolute
      monocyte count (AMC), and lymphocyte/monocyte ratio (LMR) in 359 diffuse large B
      cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide,
      doxorubicin, vincristine, and prednisone (R-CHOP). RESULTS: The median follow-up
      time of the surviving patients was 58 months. Low ALC and an elevated AMC were
      both associated with poor survival rates. Receiver operating characteristic curve
      analysis showed that LMR was the best predictor of survival, with 4.0 as the
      cutoff point. Patients with LMR <=4.0 were more likely to have an aggressive
      tumor, and this was associated with poor treatment responses. Patients with LMR
      <=4.0 at diagnosis had significantly poorer overall survival (OS) and progression
      free survival (PFS) than those with LMR >4.0. Multivariate analysis, which
      included prognostic factors of the International Prognostic Index, showed LMR
      <=4.0 to be an independent predictor for the OS (hazard ratio [HR], 2.507; 95%
      confidence interval [CI], 1.255-5.007; P = 0.009) and PFS (HR, 2.063; 95% CI,
      1.249-3.408; P = 0.005). CONCLUSIONS: The LMR at diagnosis, as a simple index
      which reflects host systemic immunity, predicts clinical outcomes in DLBCL
      patients treated with R-CHOP.

PMID- 24283207
TI  - Thyroid ablation with 1.1 GBq (30 mCi) iodine-131 in patients with papillary
      thyroid carcinoma at intermediate risk for recurrence.
AB  - BACKGROUND: Little is known about the medium- and long-term outcomes of thyroid
      ablation with 1.1 GBq (30 mCi) 131I in patients with papillary thyroid carcinoma
      who have a tumor >4 cm or accompanied by extrathyroid invasion or clinically
      detected lymph node metastases (cN1). The objective of this study was to evaluate
      the efficacy of ablation with 30 mCi 131I in this subgroup of patients and to
      report the medium-term outcomes. METHODS: We studied 152 patients with papillary
      thyroid carcinoma submitted to total thyroidectomy with apparently complete tumor
      resection, who had a tumor >4 cm or 2-4 cm accompanied by extrathyroid invasion
      or lymph node metastases, or <=2 cm accompanied by both extrathyroid invasion and
      lymph node metastases. Patients with extensive extrathyroid invasion by the
      primary tumor were excluded. Lymph node involvement was detected by
      ultrasonography or palpation (cN1). RESULTS: Forty-two patients were prepared by
      administration of recombinant human thyrotropin and 110 by levothyroxine
      withdrawal. Posttherapy whole-body scanning revealed unequivocal ectopic uptake
      in three patients. When evaluated 9-12 months after ablation, 123 patients had
      achieved complete ablation (stimulated thyroglobulin [Tg] <1 ng/mL, negative anti
      Tg antibodies, and neck ultrasonography); a new posttherapy whole-body scanning
      revealed persistent disease in 2 patients whose initial posttherapy whole-body
      scanning (obtained at the time of ablation) had already shown ectopic uptake; 12
      patients presented with a Tg >1 ng/mL and 14 had positive anti-Tg antibodies
      without apparent metastases; 1 patient had metastases not detected at the time of
      ablation. Recurrence was observed in an additional 6 patients during follow-up
      (median 76 months). There was no case of death related to the disease. Therefore,
      an activity of 30 mCi failed in only 9 (6%) patients with persistent disease or
      recurrence after ablation. None of the variables analyzed (sex, age, tumor size,
      multicentricity, extrathyroid invasion, lymph node metastases, preparation
      [recombinant human thyrotropin or levothyroxine withdrawal]) was a predictor of
      ablation failure. CONCLUSIONS: An activity of 30 mCi 131I is effective in thyroid
      ablation in patients with stage T3 and/or N1 papillary thyroid carcinoma.

PMID- 24283208
TI  - The RIAD peptidomimetic inhibits HIV-1 replication in humanized NSG mice.
AB  - BACKGROUND: Increased intracellular concentration of cyclic AMP (cAMP) in T cells
      is associated with various immunodeficiency conditions including human
      immunodeficiency virus (HIV) infection. Several reports indicate a critical role
      of activated protein kinase A (PKA) in the susceptibility of cells to HIV
      infection. We have used a cell permeable, stable peptidomimetic version (P3) of
      the RI-anchoring disruptor (RIAD), which prevents PKA interaction with A-kinase
      anchoring proteins (AKAPs). It is known that RIAD peptide abrogates effects of
      localized cAMP signalling through anchored type I PKA in lymphocytes and prevents
      murine AIDS (MAIDS) infection when expressed as a transgene in mice. METHODS AND
      RESULTS: In vitro HIV-infected human peripheral blood mononuclear cells (PBMCs)
      show reduced levels of p24 and intracellular cAMP in T cells when treated with
      RIAD peptidomimetic (RIAD-P3). Humanized NOD/SCID/IL2gammanull (NSG) mice
      infected with HIV-1 JRCSF and treated with RIAD-P3 (3.5 mg) once every 2 weeks
      showed significantly reduced levels of viral load at +28, +42 and +56 days and
      increased CD4 numbers at +56 days after the start of treatment. RIAD-P3-treated
      humanized mice had lower levels of intracellular cAMP in T cells sorted from
      splenocytes. CONCLUSIONS: Treatment with RIAD-P3 limits HIV-1 viral replication
      and stabilizes CD4 levels by mechanisms involving cAMP/PKA-I pathway in human
      PBMCs and humanized NSG mice.

PMID- 24283209
TI  - Chronic psychological stress activates BMP4-dependent extramedullary
      erythropoiesis.
AB  - Psychological stress affects different physiological processes including
      haematopoiesis. However, erythropoietic effects of chronic psychological stress
      remain largely unknown. The adult spleen contains a distinct microenvironment
      favourable for rapid expansion of erythroid progenitors in response to stressful
      stimuli, and emerging evidence suggests that inappropriate activation of stress
      erythropoiesis may predispose to leukaemic transformation. We used a mouse model
      to study the influence of chronic psychological stress on erythropoiesis in the
      spleen and to investigate potential mediators of observed effects. Adult mice
      were subjected to 2 hrs daily restraint stress for 7 or 14 consecutive days. Our
      results showed that chronic exposure to restraint stress decreased the
      concentration of haemoglobin in the blood, elevated circulating levels of
      erythropoietin and corticosterone, and resulted in markedly increased number of
      erythroid progenitors and precursors in the spleen. Western blot analysis
      revealed significantly decreased expression of both erythropoietin receptor and
      glucocorticoid receptor in the spleen of restrained mice. Furthermore, chronic
      stress enhanced the expression of stem cell factor receptor in the red pulp.
      Moreover, chronically stressed animals exhibited significantly increased
      expression of bone morphogenetic protein 4 (BMP4) in the red pulp as well as
      substantially enhanced mRNA expression levels of its receptors in the spleen.
      These findings demonstrate for the first time that chronic psychological stress
      activates BMP4-dependent extramedullary erythropoiesis and leads to the prolonged
      activation of stress erythropoiesis pathways. Prolonged activation of these
      pathways along with an excessive production of immature erythroid cells may
      predispose chronically stressed subjects to a higher risk of leukaemic
      transformation.

PMID- 24283211
TI  - Evaluation of the fibromyalgia diagnostic screen in clinical practice.
AB  - RATIONALE, AIMS AND OBJECTIVES: Fibromyalgia (FM) is challenging to diagnose,
      especially in primary care settings. The Fibromyalgia Diagnostic Screen was
      developed to facilitate the diagnosis of FM in clinical practice. The objectives
      of this study were to assess the performance of the Fibromyalgia Diagnostic
      Screen in primary care and specialty clinics, using the 1990 American College of
      Rheumatology (ACR) diagnostic criteria as the gold standard, and comparing the
      Fibromyalgia Diagnostic Screen with the London Fibromyalgia Epidemiology Study
      Screening Questionnaire (LFESSQ) and the modified 2010 ACR Fibromyalgia
      Diagnostic Criteria (ACR-FDC). METHODS: This multicenter, cross-sectional study
      included 150 adult chronic pain patients who underwent a physician-administered
      structured history and physical exam and completed the Fibromyalgia Diagnostic
      Screen, the LFESSQ and the modified ACR-FDC. The analyses determined the
      predictive ability of the Fibromyalgia Diagnostic Screen for FM. RESULTS: Item
      level analyses provided support for the response categories and predictive
      ability of most of the Fibromyalgia Diagnostic Screen items. Additionally, the
      evaluation of the Fibromyalgia Diagnostic Screen scoring models demonstrated the
      greatest accuracy in predicting an FM diagnosis with a combination of patient
      items and clinician items that included an abbreviated tender point exam
      (sensitivity 0.68, specificity, 0.82). Sensitivity of the modified ACR-FDC and
      the LFESSQ was 0.87 and 0.86, respectively, with specificity 0.62 and 0.49,
      respectively. CONCLUSIONS: The Fibromyalgia Diagnostic Screen is a useful new
      clinical tool to aid in the evaluation of FM in clinical practice.

PMID- 24283210
TI  - IL-22 contributes to TGF-beta1-mediated epithelial-mesenchymal transition in
      asthmatic bronchial epithelial cells.
AB  - BACKGROUND: Allergic asthma is characterized by airway inflammation in response
      to antigen exposure, leading to airway remodeling and lung dysfunction.
      Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling
      through the acquisition of a mesenchymal phenotype in airway epithelial cells.
      TGF-beta1 is known to promote EMT; however, other cytokines expressed in severe
      asthma with extensive remodeling, such as IL-22, may also contribute to this
      process. In this study, we evaluated the contribution of IL-22 to EMT in primary
      bronchial epithelial cells from healthy and asthmatic subjects. METHODS: Primary
      bronchial epithelial cells were isolated from healthy subjects, mild asthmatics
      and severe asthmatics (n=5 patients per group). The mRNA and protein expression
      of epithelial and mesenchymal cell markers and EMT-associated transcription
      factors was evaluated following stimulation with TGF-beta1, IL-22 and TGF
      beta1+IL-22. RESULTS: Primary bronchial epithelial cells stimulated with TGF
      beta1 underwent EMT, demonstrated by decreased expression of epithelial markers
      (E-cadherin and MUC5AC) and increased expression of mesenchymal markers (N
      cadherin and vimentin) and EMT-associated transcription factors. IL-22 alone had
      no effect on epithelial or mesenchymal gene expression. However, IL-22+TGF-beta1
      promoted the expression of some EMT transcription factors (Snail1 and Zeb1) and
      led to a more profound cadherin shift, but only in cells obtained from severe
      asthmatics. CONCLUSION: The impact of IL-22 on airway epithelial cells depends on
      the cytokine milieu and the clinical phenotype of the patient. Further studies
      are required to determine the molecular mechanism of IL-22 and TGF-beta1
      cooperativity in driving EMT in primary human bronchial epithelial cells.

PMID- 24283212
TI  - A dual gene-silencing vector system for monocot and dicot plants.
AB  - Plant virus-based gene-silencing vectors have been extensively and successfully
      used to elucidate functional genomics in plants. However, only limited virus
      induced gene-silencing (VIGS) vectors can be used in both monocot and dicot
      plants. Here, we established a dual gene-silencing vector system based on Bamboo
      mosaic virus (BaMV) and its satellite RNA (satBaMV). Both BaMV and satBaMV
      vectors could effectively silence endogenous genes in Nicotiana benthamiana and
      Brachypodium distachyon. The satBaMV vector could also silence the green
      fluorescent protein (GFP) transgene in GFP transgenic N. benthamiana. GFP
      transgenic plants co-agro-inoculated with BaMV and satBaMV vectors carrying
      sulphur and GFP genes, respectively, could simultaneously silence both genes.
      Moreover, the silenced plants could still survive with the silencing of genes
      essential for plant development such as heat-shock protein 90 (Hsp90) and Hsp70.
      In addition, the satBaMV- but not BaMV-based vector could enhance gene-silencing
      efficiency in newly emerging leaves of N. benthamiana deficient in RNA-dependant
      RNA polymerase 6. The dual gene-silencing vector system of BaMV and satBaMV
      provides a novel tool for comparative functional studies in monocot and dicot
      plants. 

PMID- 24283213
TI  - Risk factors of mild rectal bleeding in very low birth weight infants: a case
      control study.
AB  - BACKGROUND: Mild rectal bleeding (MRB) is a particular clinical entity different
      from necrotizing enterocolitis, which significantly influences neonatal care in
      preterm infants. We aimed to determine the risk factors and to evaluate
      prospectively the clinical course of MRB. METHODS: We consecutively included in a
      case-control study all infants with birth weight <= 1500 g or gestational age <=
      32 weeks admitted to our unit, and presenting MRB, defined as either isolated or
      associated with mild clinical or radiological signs. We matched each Case with
      two Controls. Clinical data before, after and at time of MRB were collected,
      together with stool cultures at time of MRB (or at similar postnatal age in
      Controls). Multiple logistic regression analysis was performed to determine
      independent risk factors for the development of MRB. RESULTS: During 4 years,
      among 823 very low birth weight (VLBW) infants admitted to our unit, 72 (8.8%)
      had MRB. The median duration of rectal bleeding was 1.1 [1-2] days and the
      fasting period lasted 2.9 [2-10] days. A relapse occurred in 24% of cases. In
      multivariate analysis, only hypertension during pregnancy (p = 0.019), growth
      restriction at onset of bleeding (p = 0.026), and exposure to ibuprofen (p =
      0.003) were independent risk factors for MRB. In Cases there were more infants
      with Clostridium Difficile in stools than in Controls (p = 0.017). CONCLUSION:
      Hypertension during pregnancy, even without intrauterine growth restriction,
      appeared to carry the same risk for MRB as exposure to ibuprofen and extrauterine
      growth restriction.

PMID- 24283214
TI  - Inhibiting caspase-6 activation and catalytic activity for neurodegenerative
      diseases.
AB  - Partnerships between industry and academia are becoming increasingly complex and
      relevant in the drive to discover innovative new medicines. We describe the
      structure of the collaboration between the University of California - San
      Francisco - Small Molecule Discovery Center (UCSF-SMDC) and Genentech to develop
      chemical matter that inhibits the activity of caspase-6. We focus on the
      scientific basis for the partnership and how the orientation- and transaction
      related barriers were overcome. We describe the division of labor that allowed
      two groups to operate as a unified team to generate multiple chemical series with
      distinct mechanisms of action. The successful structure of the agreement serves
      as a model for future collaborations at both institutions.

PMID- 24283215
TI  - The effect of a low-fat, plant-based lifestyle intervention (CHIP) on serum HDL
      levels and the implications for metabolic syndrome status - a cohort study.
AB  - BACKGROUND: Low levels of high-density lipoproteins (HDL) are considered an
      important risk factor for cardiovascular disease and constitute one of the
      criteria for the Metabolic Syndrome (MetS). Lifestyle interventions promoting a
      low-fat, plant-based eating pattern appear to paradoxically reduce cardiovascular
      risk but also HDL levels. This study examined the changes in MetS risk factors,
      in particular HDL, in a large cohort participating in a 30-day lifestyle
      intervention that promoted a low-fat, plant-based eating pattern. METHODS:
      Individuals (n = 5,046; mean age = 57.3 +/- 12.9 years; 33.5% men, 66.5% women)
      participating in a in a Complete Health Improvement Program (CHIP) lifestyle
      intervention within the United States were assessed at baseline and 30 days for
      changes in body mass index (BMI), blood pressure (BP), lipid profile and fasting
      plasma glucose (FPG). RESULTS: HDL levels decreased by 8.7% (p<0.001) despite
      significant reductions (p<0.001) in BMI (-3.2%), systolic BP (-5.2%), diastolic
      BP (-5.2%), triglycerides (TG; -7.7%), FPG (-6.3%), LDL (-13.0%), total
      cholesterol (TC, -11.1%), TC: HDL ratio (-3.2%), and LDL: HDL ratio (-5.3%).
      While 323 participants classified as having MetS at program entry no longer had
      this status after the 30 days, 112 participants acquired the MetS classification
      as a result of reduction in their HDL levels. CONCLUSIONS: When people move
      towards a low-fat, plant-based diet, HDL levels decrease while other indicators
      of cardiovascular risk improve. This observation raises questions regarding the
      value of using HDL levels as a predictor of cardiovascular risk in populations
      who do not consume a typical western diet. As HDL is part of the assemblage of
      risk factors that constitute MetS, classifying individuals with MetS may not be
      appropriate in clinical practice or research when applying lifestyle
      interventions that promote a plant-based eating pattern.

PMID- 24283217
TI  - STAT3 mutations are frequent in T-cell large granular lymphocytic leukemia with
      pure red cell aplasia.
AB  - T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative
      disorder and can cooccur in the context of pure red cell aplasia (PRCA). The aim
      of the current study was to analyze the signal transducer and activator of
      transcription 3 (STAT3) mutation status and its clinical significance in T-LGLL.
      We found STAT3 mutations in 21.4% of patients with T-LGLL. High beta2-MG (beta2
      microglobulin) levels (P = 0.005), neutropenia (P = 0.018) and PRCA (P = 0.001)
      all displayed a significant association with STAT3 mutations. In univariate
      analysis, treatment-free survival (TFS) was affected by STAT3 mutation status
      (P=0.008) and beta2-MG (P = 0.006). Our results demonstrate the remarkable
      correlation of STAT3 mutation with PRCA, neutropenia and beta2-MG. 

PMID- 24283216
TI  - Association analyses for dopamine receptor gene polymorphisms and weight status
      in a longitudinal analysis in obese children before and after lifestyle
      intervention.
AB  - BACKGROUND: Dopamine receptors are involved in midbrain reward circuit
      activation. Polymorphisms in two dopamine receptor genes, DRD2 and DRD4, have
      been associated with altered perception of food reward and weight gain. The
      objective of this study was to determine whether the same risk alleles were
      associated with overweight/obesity and with lower reduction of overweight after a
      1-year lifestyle intervention. METHODS: In a longitudinal study the association
      of polymorphisms in DRD2 (rs18000497, risk allele: T, formerly A1 allele at the
      TaqI A1 polymorphism) and DRD4 (variable number of tandem repeats (VNTR); 48 bp
      repeat in exon III; risk alleles: 7 repeats or longer: 7R+) was tested on weight
      loss success following a 1-year lifestyle childhood obesity intervention
      (OBELDICKS). An additional exploratory cross-sectional case-control study was
      performed to compare the same DRD polymorphisms in these overweight/obese
      children and adolescents versus lean adult controls. Subjects were 423 obese and
      28 overweight children participating in lifestyle intervention (203 males), age
      median 12.0 (interquartile range 10.0-13.7) years, body mass index - standard
      deviation score (BMI-SDS) 2.4 +/- 0.5; 583 lean adults (232 males); age median
      25.3 (interquartile range 22.5-26.8) years, BMI 19.1 +/- 1.9 kg/m2. BMI, BMI-SDS
      and skinfold thickness measures were assessed at baseline and after 1 year;
      genotyping was performed for DRD2 risk variant rs1800497 and DRD4 exon III VNTR.
      RESULTS: The DRD2 genotype had a nominal effect on success in the weight loss
      intervention. The weakest BMI-SDS reduction was in children homozygous for two
      rs1800497 T-alleles (n = 11) compared to the combined group with zero (n = 308)
      or one (n = 132) rs1800497 T-allele (-0.08 +/- 0.36 vs. -0.28 +/- 0.34; p <
      0.05). There was no association between the DRD4 VNTR alleles and genotypes and
      success in the weight loss intervention. No associations of the risk alleles of
      the DRD2 and DRD4 polymorphisms and obesity were observed in the cross-sectional
      part of the study. CONCLUSIONS: We did not find association between polymorphisms
      in DRD2 and DRD4 genes and weight status. However, obese carriers of two DRD2
      rs1800497 T-alleles may be at risk for weak responses to lifestyle interventions
      aimed at weight reduction. TRIAL REGISTRATION: Obesity intervention program
      "Obeldicks" is registered at clinicaltrials.gov (NCT00435734).

PMID- 24283219
TI  - Antiproliferative evaluation of N-sulfonyl-2-alkyl-six membered azacycles. A QSAR
      study.
AB  - A series of functionalized N-sulfonyl-piperidines and N-sulfonyl
      tetrahydropyridines were evaluated for their antiproliferative activity against
      the representative panel of human solid tumor cells A2780 (ovarian), SW1573 (non
      small cell lung) and WiDr (colon). The SAR study showed for WiDr cells a
      correlation between the biological activity and the length of the N-sulfonyl
      group, the nature of the substituents and the type of alkyl side chain. Further
      QSAR studies indicate that the size and nature of the N-sulfonyl group, the
      atomic polarizability (MP) and the partition coefficient are the most important
      descriptors for the activity. The major contribution is the size (F05C-S) of the
      N-sulfonyl group. 

PMID- 24283218
TI  - Inhibition of tetrodotoxin-resistant sodium current in dorsal root ganglia
      neurons mediated by D1/D5 dopamine receptors.
AB  - BACKGROUND: Dopaminergic fibers originating from area A11 of the hypothalamus
      project to different levels of the spinal cord and represent the major source of
      dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the
      synthesis of catecholamines, is expressed in 8-10% of dorsal root ganglia (DRG)
      neurons, suggesting that dopamine may be released in the dorsal root ganglia.
      Dopamine has been shown to modulate calcium current in DRG neurons, but the
      effects of dopamine on sodium current and on the firing properties of small DRG
      neurons are poorly understood. RESULTS: The effects of dopamine and dopamine
      receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium
      current recorded from acutely dissociated small (diameter <= 25 MUm) DRG neurons.
      Dopamine (20 MUM) and SKF 81297 (10 MUM) caused inhibition of TTX-R sodium
      current in small DRG neurons by 23% and 37%, respectively. In contrast,
      quinpirole (20 MUM) had no effects on the TTX-R sodium current. Inhibition by SKF
      81297 of the TTX-R sodium current was not affected when the protein kinase A
      (PKA) activity was blocked with the PKA inhibitory peptide (6-22), but was
      greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC
      inhibitory peptide (19-36), suggesting that activation of D1/D5 dopamine
      receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in
      small DRG neurons, but not D2 dopamine receptors, was confirmed by Western
      blotting and immunofluorescence analysis. In current clamp experiments, the
      number of action potentials elicited in small DRG neurons by current injection
      was reduced by ~ 30% by SKF 81297. CONCLUSIONS: We conclude that activation of
      D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated
      nociceptive neurons and dampens their intrinsic excitability by reducing the
      number of action potentials in response to stimulus. Increasing or decreasing
      levels of dopamine in the dorsal root ganglia may serve to adjust the sensitivity
      of nociceptors to noxious stimuli.

PMID- 24283220
TI  - Barriers to antiretroviral treatment access for injecting drug users living with
      HIV in Chennai, South India.
AB  - India's National AIDS Control Organization provides free antiretroviral treatment
      (ART) to people living with HIV (PLHIV), including members of marginalized groups
      such as injecting drug users (IDUs). To help inform development of interventions
      to enhance ART access, we explored barriers to free ART access at government ART
      centers for IDUs living with HIV in Chennai by conducting three focus groups (n =
      19 IDUs) and four key informant interviews. Data were explored using framework
      analysis to identify categories and derive themes. We found interrelated barriers
      at the family and social, health-care system, and individual levels. Family and
      social level barriers included lack of family support and fear of societal
      discrimination, as well as unmet basic needs, including food and shelter. Health
      care system barriers included actual or perceived unfriendly hospital environment
      and procedures such as requiring proof of address and identity from PLHIV,
      including homeless IDUs; provider perception that IDUs will not adhere to ART,
      resulting in ART not being initiated; actual or perceived inadequate counseling
      services and lack of confidentiality; and lack of effective linkages between ART
      centers, needle/syringe programs, and drug dependence treatment centers.
      Individual-level barriers included active drug use, lack of self-efficacy in ART
      adherence, low motivation to initiate ART stemming from a fatalistic attitude,
      and inadequate knowledge about ART. These findings indicate that to facilitate
      IDUs gaining access to ART, systemic changes are needed, including steps to make
      the environment and procedures at government ART centers more IDU-friendly and
      steps to decrease HIV- and drug use-related stigma and discrimination faced by
      IDUs from the general public and health-care providers. Housing support for
      homeless IDUs and linkage of IDUs with drug dependence treatment are also
      essential.

PMID- 24283221
TI  - MicroRNA-323-3p with clinical potential in rheumatoid arthritis, Alzheimer's
      disease and ectopic pregnancy.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are a group of noncoding RNAs,~ 20 - 22
      nucleotides in length, that repress target gene expression through mRNA
      degradation and translation inhibition. The gene encoding miR-323-3p, which is a
      biomarker in immune and inflammatory responses, exists in a miRNA cluster in
      chromosomal region 14q32.31. It has been shown that miR-323-3p associates with
      the pathogenesis of several diseases, such as rheumatoid arthritis, Alzheimer's
      disease and ectopic pregnancy. AREAS COVERED: This review provides a current view
      on the association of miR-323-3p with several human diseases and is focused on
      the recent studies of miR-323-3p regulation, discussing its potential as an
      epigenetic biomarker and therapeutic target for these diseases. In particular,
      the mechanisms of miR-323-3p in these diseases and how miR-323-3p is regulated
      are also discussed. EXPERT OPINION: Although the exact role of miR-323-3p in
      these diseases has not been fully elucidated, targeting miR-323-3p may serve as a
      promising therapy strategy.

PMID- 24283223
TI  - The quest for an HIV-1 vaccine--moving forward.

PMID- 24283222
TI  - The longitudinal interplay between negative and positive symptom trajectories in
      patients under antipsychotic treatment: a post hoc analysis of data from a
      randomized, 1-year pragmatic trial.
AB  - BACKGROUND: Schizophrenia is a highly heterogeneous disorder with positive and
      negative symptoms being characteristic manifestations of the disease. While these
      two symptom domains are usually construed as distinct and orthogonal, little is
      known about the longitudinal pattern of negative symptoms and their linkage with
      the positive symptoms. This study assessed the temporal interplay between these
      two symptom domains and evaluated whether the improvements in these symptoms were
      inversely correlated or independent with each other. METHODS: This post hoc
      analysis used data from a multicenter, randomized, open-label, 1-year pragmatic
      trial of patients with schizophrenia spectrum disorder who were treated with
      first- and second-generation antipsychotics in the usual clinical settings. Data
      from all treatment groups were pooled resulting in 399 patients with complete
      data on both the negative and positive subscale scores from the Positive and
      Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling
      combined with interplay matrix was used to identify the latent trajectory
      patterns in terms of both the negative and positive symptoms. Pearson correlation
      coefficients were calculated to examine the relationship between the changes of
      these two symptom domains within each combined trajectory pattern. RESULTS: We
      identified four distinct negative symptom trajectories and three positive symptom
      trajectories. The trajectory matrix formed 11 combined trajectory patterns, which
      evidenced that negative and positive symptom trajectories moved generally in
      parallel. Correlation coefficients for changes in negative and positive symptom
      subscale scores were positive and statistically significant (P < 0.05). Overall,
      the combined trajectories indicated three major distinct patterns: (1) dramatic
      and sustained early improvement in both negative and positive symptoms (n = 70,
      18%), (2) mild and sustained improvement in negative and positive symptoms (n =
      237, 59%), and (3) no improvement in either negative or positive symptoms (n =
      82, 21%). CONCLUSIONS: This study of symptom trajectories over 1 year shows that
      changes in negative and positive symptoms were neither inversely nor
      independently related with each other. The positive association between these two
      symptom domains supports the notion that different symptom domains in
      schizophrenia may depend on each other through a unified upstream pathological
      disease process.

PMID- 24283224
TI  - ARMC5 mutations in macronodular adrenal hyperplasia with Cushing's syndrome.
AB  - BACKGROUND: Corticotropin-independent macronodular adrenal hyperplasia may be an
      incidental finding or it may be identified during evaluation for Cushing's
      syndrome. Reports of familial cases and the involvement of both adrenal glands
      suggest a genetic origin of this condition. METHODS: We genotyped blood and tumor
      DNA obtained from 33 patients with corticotropin-independent macronodular adrenal
      hyperplasia (12 men and 21 women who were 30 to 73 years of age), using single
      nucleotide polymorphism arrays, microsatellite markers, and whole-genome and
      Sanger sequencing. The effects of armadillo repeat containing 5 (ARMC5)
      inactivation and overexpression were tested in cell-culture models. RESULTS: The
      most frequent somatic chromosome alteration was loss of heterozygosity at 16p (in
      8 of 33 patients for whom data were available [24%]). The most frequent mutation
      identified by means of whole-genome sequencing was in ARMC5, located at 16p11.2.
      ARMC5 mutations were detected in tumors obtained from 18 of 33 patients (55%). In
      all cases, both alleles of ARMC5 carried mutations: one germline and the other
      somatic. In 4 patients with a germline ARMC5 mutation, different nodules from the
      affected adrenals harbored different secondary ARMC5 alterations. Transcriptome
      based classification of corticotropin-independent macronodular adrenal
      hyperplasia indicated that ARMC5 mutations influenced gene expression, since all
      cases with mutations clustered together. ARMC5 inactivation decreased
      steroidogenesis in vitro, and its overexpression altered cell survival.
      CONCLUSIONS: Some cases of corticotropin-independent macronodular adrenal
      hyperplasia appear to be genetic, most often with inactivating mutations of
      ARMC5, a putative tumor-suppressor gene. Genetic testing for this condition,
      which often has a long and insidious prediagnostic course, might result in
      earlier identification and better management. (Funded by Agence Nationale de la
      Recherche and others.).

PMID- 24283226
TI  - Ventilator-induced lung injury.

PMID- 24283225
TI  - Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.
AB  - BACKGROUND: Bilateral macronodular adrenal hyperplasia is a rare cause of primary
      adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of
      cortisol suppresses the release of corticotropin by pituitary corticotrophs,
      which results in low plasma corticotropin levels. Thus, the disease has been
      termed corticotropin-independent macronodular adrenal hyperplasia. We examined
      the abnormal production of corticotropin in these hyperplastic adrenal glands.
      METHODS: We obtained specimens of hyperplastic macronodular adrenal tissue from
      30 patients with primary adrenal disease. The corticotropin precursor
      proopiomelanocortin and corticotropin expression were assessed by means of a
      polymerase-chain-reaction assay and immunohistochemical analysis. The production
      of corticotropin and cortisol was assessed in 11 specimens with the use of
      incubated explants and cell cultures coupled with hormone assays. Corticotropin
      levels were measured in adrenal and peripheral venous blood samples from 2
      patients. RESULTS: The expression of proopiomelanocortin messenger RNA (mRNA) was
      detected in all samples of hyperplastic adrenal tissue. Corticotropin was
      detected in steroidogenic cells arranged in clusters that were disseminated
      throughout the adrenal specimens. Adrenal corticotropin levels were higher in
      adrenal venous blood samples than in peripheral venous samples, a finding that
      was consistent with local production of the peptide within the hyperplastic
      adrenals. The release of adrenal corticotropin was stimulated by ligands of
      aberrant membrane receptors but not by corticotropin-releasing hormone or
      dexamethasone. A semiquantitative score for corticotropin immunostaining in the
      samples correlated with basal plasma cortisol levels. Corticotropin-receptor
      antagonists significantly inhibited in vitro cortisol secretion. CONCLUSIONS:
      Cortisol secretion by the adrenals in patients with macronodular hyperplasia and
      Cushing's syndrome appears to be regulated by corticotropin, which is produced by
      a subpopulation of steroidogenic cells in the hyperplastic adrenals. Thus, the
      hypercortisolism associated with bilateral macronodular adrenal hyperplasia
      appears to be corticotropin-dependent. (Funded by the Agence Nationale de la
      Recherche and others.).

PMID- 24283227
TI  - Images in clinical medicine. Hallux varus.

PMID- 24283228
TI  - Case records of the Massachusetts General Hospital. Case 37-2013. A 41-year-old
      woman with malaise and chest and abdominal pain.

PMID- 24283229
TI  - Heredity and cortisol regulation in bilateral macronodular adrenal hyperplasia.

PMID- 24283230
TI  - Picking the lock on pluripotency.

PMID- 24283232
TI  - RAS mutations in colorectal cancer.

PMID- 24283231
TI  - Contagious diseases in the United States from 1888 to the present.

PMID- 24283233
TI  - RAS mutations in colorectal cancer.

PMID- 24283234
TI  - Chromothripsis in uterine leiomyomas.

PMID- 24283235
TI  - Chromothripsis in uterine leiomyomas.

PMID- 24283236
TI  - A novel channelopathy in pulmonary arterial hypertension.

PMID- 24283237
TI  - A novel channelopathy in pulmonary arterial hypertension.

PMID- 24283238
TI  - A novel channelopathy in pulmonary arterial hypertension.

PMID- 24283239
TI  - Primary hyperoxaluria.

PMID- 24283240
TI  - Primary hyperoxaluria.

PMID- 24283241
TI  - Engineered in India--patent law 2.0.

PMID- 24283242
TI  - A new era in noninvasive prenatal testing.

PMID- 24283243
TI  - A new era in noninvasive prenatal testing.

PMID- 24283244
TI  - A new era in noninvasive prenatal testing.

PMID- 24283245
TI  - The great east Japan earthquake and out-of-hospital cardiac arrest.

PMID- 24283247
TI  - Images in clinical medicine. Cerebrospinal fluid otorhinorrhea.

PMID- 24283249
TI  - The validity of physical therapy assessment of low back pain via
      telerehabilitation in a clinical setting.
AB  - BACKGROUND: Back pain is a common and disabling condition for people in rural and
      remote areas. In these areas, access to rehabilitation services is limited by
      service availability. Telerehabilitation is suggested as a solution for providing
      physical therapy services; however, the validity of clinical assessment is
      largely unproven. The aim of this study was to establish the validity of
      clinically pragmatic remote assessment of spinal posture, active movements of the
      lumbar spine, and the passive straight leg raise (SLR) test. SUBJECTS AND
      METHODS: Face-to-face physical therapist assessment was compared with
      telerehabilitation assessment of spinal posture, active movements of the lumbar
      spine, and the SLR test. Twenty-six participants recruited from a rural
      population with current or recent low back pain (LBP) were assessed by a face-to
      face physical therapist and a remote physical therapist. Pain, disability, and
      clinical measurements were assessed. Outcomes were compared to establish
      agreement. RESULTS: High levels of agreement were found with detecting pain with
      specific lumbar movements, eliciting symptoms, and sensitizing the SLR test.
      Moderate agreement occurred with identifying the worst lumbar spine movement
      direction, SLR range of motion, and active lumbar spine range of motion. Poor
      agreement occurred with postural analysis and identifying reasons for limitations
      to lumbar movements. CONCLUSIONS: Conducted in a rural clinical setting, this
      study validates elements of the physical assessment of the lumbar spine and
      identifies technical and clinical issues to be addressed by future research.
      Important components of the standard musculoskeletal assessment of LBP are valid
      via telerehabilitation in a clinical setting.

PMID- 24283248
TI  - Detection of TP53 dysfunction in chronic lymphocytic leukemia by an in vitro
      functional assay based on TP53 activation by the non-genotoxic drug Nutlin-3: a
      proposal for clinical application.
AB  - BACKGROUND: TP53 defects, i.e., 17p13 deletion and/or nucleotide mutations,
      associate with short survival and chemorefractoriness in chronic lymphocytic
      leukemia (CLL). In this context, since direct sequencing of the TP53 gene does
      not evaluate TP53 functionality, a functional assessment of TP53 pathway may be
      of interest to identify high risk CLL. By taking advantage of a training cohort
      of 100 CLL and a validation cohort of 40 CLL with different patterns of TP53
      mutation/deletion by FISH and sequencing, we propose an in-vitro assay in which
      the modulation of TP53 protein and CDKN1A mRNA were investigated upon 24-hour
      exposure of CLL cells to Nutlin-3. METHODS: The functional assay was set-up on
      cell lines recapitulating all TP53 genotypes (EHEB, TP53(wt/wt); RAJI,
      TP53(mut/wt); MEC-1 and MAVER1, TP53(mut/del); HL-60, TP53(del/del)) and
      evaluated in two multi-institutional cohorts, purposely enriched in CLL bearing
      TP53 disruption: a training cohort of 100 cases and a validation cohort of 40
      cases, both characterized by FISH and TP53 direct sequencing. Cells were exposed
      to 10 uM Nutlin-3 for 24 hours; TP53 accumulation was evaluated by Western
      blotting; TP53 transcriptional activity was determined by quantitative realtime
      PCR (qRT-PCR) of the TP53 target gene CDKN1A. RESULTS: According to TP53 protein
      modulation, in the training cohort we identified: (i) 63 cases (51 TP53wt/wt, 12
      TP53del/wt) with absence of basal TP53 and induction after treatment (normal
      pattern); (ii) 18 cases (3 TP53(mut/wt), 15 TP53(mut/del)) with high basal TP53
      without increase after treatment (mutant pattern); (iii) 19 cases (5
      TP53(mut/wt); 3 TP53(mut/del); 11 TP53(wt/wt)) with basal TP53 that increases
      upon treatment (intermediate pattern). Evaluation of CDKN1A mRNA levels upon
      Nutlin-3 exposure showed that the 26 TP53 mutated (TP53(mut/del) or TP53(mut/wt))
      cases had lower induction levels than the majority (57/63) of cases with normal
      pattern, and 10/12 cases with intermediate pattern without evidence of TP53
      derangement by FISH and sequencing. These results were confirmed in the
      independent validation cohort of 40 cases (13 TP53(wt/wt), 3 TP53(del/wt), 12
      TP53(mut/del), 12 TP53(mut/wt)). CONCLUSIONS: The proposed functional assay may
      integrate the conventional analyses for the identification of TP53 dysregulated
      CLL.

PMID- 24283250
TI  - Electronic and remote prescribing: administrative, regulatory, technical, and
      clinical standards and guidelines, April 2013.
AB  - This document recommends standards to be applied in a licensed prescriber's
      transition to electronic (e-prescribing) and remote prescribing. A perspective
      inherent in this document is that remote prescribing or telemedical e-prescribing
      can only be understood within the larger context of e-prescribing, a relatively
      new tool in the American healthcare toolkit. The purpose of this document is to
      inform and assist individuals and organizations in providing safe and effective e
      prescribing and remote prescribing services on behalf of patients. A list of
      additional resources and a workflow for e-prescribing are offered as well.

PMID- 24283251
TI  - Older people's attitudes toward interactive voice response systems.
AB  - BACKGROUND: Interactive voice response (IVR) systems are computer programs that
      interact with people to provide a number of services from business to healthcare.
      The healthcare applications are particularly relevant to older adults because
      they are important consumers of medical services. However, research has found
      that older adults can experience significant difficulties with IVR and have more
      negative attitudes toward the technology. SUBJECTS AND METHODS: Seniors'
      attitudes appear to be related to their most recent experiences with IVR systems.
      The objective of this study was to examine attitudes toward four commercial or
      governmental IVR systems and how these attitudes relate to participants' ability
      to interact with the technology in a sample of 185 community-dwelling older (>65
      year-old) adults. We also examined the effects of several demographic factors on
      both success and attitudes toward automated systems. RESULTS: We found a
      significant positive correlation between IVR success and attitudes toward IVR.
      However, a large subset of our sample gave high ratings despite experiencing
      significant difficulties with the systems. These participants tended to have
      lower full scale IQ. No gender differences emerged in terms of attitudes and
      ability to interact with IVR systems. CONCLUSIONS: Results also indicated that
      older adults in our sample viewed the IVR interaction as particularly demanding
      on attention and concentration abilities.

PMID- 24283252
TI  - A case-control validation of Type D personality in Greek patients with stable
      coronary heart disease.
AB  - BACKGROUND: Type D personality has been associated with a variety of emotional
      and social difficulties as well as with poor prognosis in patients with
      established coronary heart disease (CHD). We examined the psychometric properties
      and validity of the Type D Scale-14 (DS14) and the prevalence of Type D
      personality among Greek patients with CHD while taking into account demographic;
      clinical, such as diabetes mellitus, hypertension, and hypercholesterolemia; as
      well as psychological variables such as depression, anxiety, and psychological
      stress. METHODS: Ninety-six patients with stable coronary heart disease and 80
      healthy participants from the general population completed the Greek version of
      the DS14 and the Hospital Anxiety and Depression Scale (HADS). RESULTS:
      Cronbach's alpha coefficient for the negative affectivity (NA) and social
      inhibition (SI) subscales was 0.83 and 0.72 for the CHD and 0.88 and 0.76 for the
      control group, respectively. Internal-structural validity was assessed by a
      factor analysis (two-factor solution), and the factor structure of the original
      DS14 was replicated. Using the standardized cutoff point of NA >=10 and SI >=10,
      instead of the median scores, in order to have compatible results with the
      majority of studies, the prevalence of Type D personality was 51% for the CHD
      patients and 13% for the control group. Higher NA and SI were connected with
      higher anxiety, depression, and total psychological stress. Finally, more
      patients with CHD and Type D personality than those without were diagnosed with
      type 2 diabetes; however, no differences were observed in hypertension or
      hypercholesterolemia. CONCLUSIONS: These results indicate that the Type D
      construct is reliable and valid in a Greek population. The prevalence of Type D
      personality was higher in patients with stable coronary heart disease than in
      people from the general population. The DS14 subscales were positively correlated
      with higher anxiety, depression, and total psychological stress. Regarding other
      CHD risk factors, only diabetes mellitus was found more frequently in CHD
      patients with Type D personality.

PMID- 24283253
TI  - New therapeutic perspectives on protein-bound uremic toxins in chronic kidney
      disease.
AB  - The uremic syndrome is a complex mosaic of clinical alterations that may be
      attributable to one or more of these different solutes. Uremic symptoms in
      patients with chronic kidney disease are primarily a consequence of inadequate
      removal and subsequent accumulation of organic products normally metabolized or
      excreted by the kidney. 

PMID- 24283254
TI  - Molecular recognition of aliphatic diamines by 3,3'-di(trifluoroacetyl)-1,1'-bi-2
      naphthol.
AB  - The fluorescent responses of 3,3'-di(trifluoroacetyl)-1,1'-bi-2-naphthol toward a
      variety of amines have been studied. It was found that the aliphatic primary 1,2-
      and 1,5-diamines can greatly enhance the fluorescence of this compound, but under
      the same conditions, primary, secondary, and tertiary monoamines cannot turn on
      the fluorescence of this compound. In addition, this compound was shown to be an
      enantioselective and diastereoselective fluorescent sensor for chiral diamines.
      UV absorption and NMR spectroscopic methods have been used to study the
      interaction of the sensor with amines. These studies have demonstrated that the
      intramolecular OH...O?C hydrogen bonding of the sensor is important for both the
      reactivity of its trifluoroacetyl group with the amines and its fluorescent
      responses. The interaction of both of the two amine groups of a diamine molecule
      with the sensor is essential for the observed fluorescent sensitivity and
      selectivity. 

PMID- 24283255
TI  - Arsenic species formed from arsenopyrite weathering along a contamination
      gradient in Circumneutral river floodplain soils.
AB  - Arsenic is a toxic trace element, which commonly occurs as contaminant in
      riverine floodplains and associated wetlands affected by mining and ore
      processing. In this study, we investigated the solid-phase speciation of As in
      river floodplain soils characterized by circumneutral pH (5.7-7.1) and As
      concentrations of up to 40.3 g/kg caused by former mining of arsenopyrite-rich
      ores. Soil samples collected in the floodplain of Ogosta River (Bulgaria) were
      size-fractionated and subsequently analyzed using a combination of X-ray
      fluorescence (XRF) spectrometry, powder X-ray diffraction (XRD), X-ray absorption
      spectroscopy (XAS), and selective chemical extraction of poorly crystalline
      mineral phases. Arsenic and Fe were found to be spatially correlated and both
      elements were strongly enriched in the fine soil particle size fractions (<2 MUm
      and 2-50 MUm). Between 14 and 82% of the total As was citrate-ascorbate
      extractable. Molar As/Fe ratios were as high as 0.34 in the bulk soil extracts
      and increased up to 0.48 in extracts of the fine particle size fractions. Arsenic
      K-edge XAS spectra showed the predominance of As(V) and were well fitted with a
      reference spectrum of As(V) adsorbed to ferrihydrite. Whereas no As(III) was
      detected, considerable amounts of As(-I) were present and identified as
      arsenopyrite originating from the mining waste. Iron K-edge XAS revealed that in
      addition to As(V) adsorbed to ferrihydrite, X-ray amorphous As(V)-rich hydrous
      ferric oxides ("As-HFO") with a reduced number of corner-sharing FeO6 octahedra
      relative to ferrihydrite were the dominating secondary As species in the soils.
      The extremely high concentrations of As in the fine particle size fractions (up
      to 214 g/kg) and its association with poorly crystalline Fe(III) oxyhydroxides
      and As-HFO phases suggest a high As mobilization potential under both oxic and
      anoxic conditions, as well as a high bioaccessibility of As upon ingestion,
      dermal contact, or inhalation by humans or animals. 

PMID- 24283256
TI  - Critical research concepts in tuberculosis vaccine development.
AB  - A new and improved vaccine against tuberculosis (TB) would provide a powerful
      tool to conquer one of the most insidious infectious diseases of mankind.
      Protection afforded by bacillus Calmette-Guerin (BCG) has been shown to be
      limited and inconsistent, especially in adults that are known to transmit TB
      disease. In the last two decades, several new vaccines have been developed and
      tested with the aim to elicit robust and long-lived T-cell responses against
      Mycobacterium tuberculosis antigens. Although much progress has been made in the
      TB vaccine field, there is an urgent need to address critical research questions
      about TB immunity with a special focus on designing vaccines aimed at preventing
      infection and transmission of TB. Here, we discuss the rationale behind the
      current immunization strategies being implemented for TB vaccines and provide
      some suggestions for hypothesis driven research to encourage the development of
      novel TB vaccines. 

PMID- 24283257
TI  - Enhanced development of auditory change detection in musically trained school
      aged children: a longitudinal event-related potential study.
AB  - Adult musicians show superior auditory discrimination skills when compared to non
      musicians. The enhanced auditory skills of musicians are reflected in the
      augmented amplitudes of their auditory event-related potential (ERP) responses.
      In the current study, we investigated longitudinally the development of auditory
      discrimination skills in musically trained and nontrained individuals. To this
      end, we recorded the mismatch negativity (MMN) and P3a responses from children
      who play a musical instrument and age-matched children with no musical training
      at ages 7, 9, 11, and 13. Basic auditory processing was investigated by recording
      ERPs in the Multi-Feature Paradigm that included frequency, duration, intensity,
      location, and gap deviants. The detection of musically more relevant sound
      changes was examined in an oddball paradigm with major chords as standards and
      minor chords as deviants. The musically trained children showed larger increase
      in MMN and P3a amplitudes with age for the chord deviants than the control
      children. There was also a strong trend (p = .054) for larger increase in MMN
      amplitude in the musically trained children for the location deviant. As no group
      differences in response amplitudes were evident at the early stages of the
      training, our results suggest that the superior neural auditory discrimination in
      adult musicians is due to training and not pre-existing differences between
      musicians and non-musicians. 

PMID- 24283258
TI  - The combination of attenuated Newcastle disease (ND) vaccine with rHVT-ND vaccine
      at 1 day old is more protective against ND virus challenge than when combined
      with inactivated ND vaccine.
AB  - The recurrent outbreaks of fatal Newcastle disease (ND) in commercial poultry
      flocks throughout the world indicate that routine vaccinations are failing to
      sufficiently induce the high levels of immunity necessary to control ND. There is
      a need for vaccination programmes that could be initiated at 1-day-old for mass
      application and which would induce a long-lasting immunity, with no need for a
      booster vaccination at a later age. In this context, the duration of immunity
      delivered by a vaccination programme including a recombinant herpesvirus of
      turkeys expressing the F gene of ND virus (rHVT-ND) and live ND vaccine at 1-day
      old was compared with a classical programme that included a conventional live and
      an inactivated ND vaccine at the same age in commercial layer chickens. The
      humoral, cell-mediated and local immunity were followed weekly and birds were
      challenged with a viscerotropic velogenic ND virus strain at 6 and 10 weeks of
      age. We determined that immunity induced by the vaccination programme involving
      the rHVT-ND vaccine was more protective than that provided by the conventional
      vaccine-based regime. This might be related to a T-helper type 1 (Th1) cellular
      driven immunological response, in contrast to the T-helper type 2 (Th2) humoral
      oriented immune response provided by the current conventional vaccine-based
      vaccination programmes. 

PMID- 24283259
TI  - Making sense of the mayhem behind shape control in the synthesis of gold
      nanoparticles.
AB  - The formation of anisotropic Au nanoparticles predominantly follows one of two
      growth pathways: (1) kinetic control or (2) selective surface passivation. This
      Perspective describes the mechanisms that control Au nanoparticle shape via these
      pathways in the context of three basic chemical parameters: metal complex
      reduction potential, metal ion availability, and adsorbate binding strength.
      These chemical parameters influence the crystallinity and surface facets of the
      Au nanoparticles, thus dictating particle shape. Understanding nanoparticle
      growth mechanisms in terms of simple chemical principles enables mechanistic
      insights to be more easily applied to other syntheses and gives them greater
      predictive power in the development of new preparations of metal nanoparticles
      with well-defined shapes. Background information regarding the growth of Au
      nanoparticles with control over shape is also provided, along with a perspective
      on unanswered mechanistic questions in noble-metal nanoparticle synthesis and
      promising directions for future studies. 

PMID- 24283260
TI  - Highly rearranged and size-variable chloroplast genomes in conifers II clade
      (cupressophytes): evolution towards shorter intergenic spacers.
AB  - Although conifers are of immense ecological and economic value, bioengineering of
      their chloroplasts remains undeveloped. Understanding the chloroplast genomic
      organization of conifers can facilitate their bioengineering. Members of the
      conifer II clade (or cupressophytes) are highly diverse in both morphologic
      features and chloroplast genomic organization. We compared six cupressophyte
      chloroplast genomes (cpDNAs) that represent four of the five cupressophyte
      families, including three genomes that are first reported here (Agathis dammara,
      Calocedrus formosana and Nageia nagi). The six cupressophyte cpDNAs have lost a
      pair of large inverted repeats (IRs) and vary greatly in size, organization and
      tRNA copies. We demonstrate that cupressophyte cpDNAs have evolved towards
      reduced size, largely due to shrunken intergenic spacers. In cupressophytes,
      cpDNA rearrangements are capable of extending intergenic spacers, and synonymous
      mutations are negatively associated with the size and frequency of
      rearrangements. The variable cpDNA sizes of cupressophytes may have been shaped
      by mutational burden and genomic rearrangements. On the basis of cpDNA
      organization, our analyses revealed that in gymnosperms, cpDNA rearrangements are
      phylogenetically informative, which supports the 'gnepines' clade. In addition,
      removal of a specific IR influences the minimal rearrangements required for the
      gnepines and cupressophyte clades, whereby Pinaceae favours the removal of IRB
      but cupressophytes exclusion of IRA. This result strongly suggests that different
      IR copies have been lost from conifers I and II. Our data help understand the
      complexity and evolution of cupressophyte cpDNAs. 

PMID- 24283262
TI  - Unravelling bacteriophage phi11 requirements for packaging and transfer of mobile
      genetic elements in Staphylococcus aureus.
AB  - Bacteriophages play a major role in spreading mobile genetic elements (MGEs)
      encoded genes among bacterial populations. In spite of this, the molecular
      requirements for building phage transducing particles have not been completely
      deciphered. Here, we systematically inactivated each ORF from the packaging and
      lysis modules of the staphylococcal phage phi11, used as a model for the
      Siphoviridae phages infecting Gram-positive bacteria, and determined their
      functional role in transferring different MGEs including plasmids, staphylococcal
      pathogenicity islands (SaPIs) and the phage itself. In a previous report, we
      identified seven of these ORFs as being required for the production of functional
      phage or SaPI particles. In this report, we have completed the mutational
      analysis and have identified and characterized 15 additional phage-encoded
      proteins required for the production of mature phage, SaPI, or transducing
      particles. Apart from these, we have not yet ascertained any specific function
      for the six remaining phi11 genes, though they are highly conserved among the
      staphylococcal bacteriophages. To the best of our knowledge, this study
      represents the first systematic deletion analysis of all the ORFs comprising the
      morphogenetic and lysis modules of a phage, clearly defining the molecular
      requirements involved in phage-mediated MGEs transfer. 

PMID- 24283261
TI  - Enhancing bone marrow regeneration by SALL4 protein.
AB  - Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to
      treat a variety of blood diseases. The success of hematopoietic recovery is of
      high importance and closely related to the patient's morbidity and mortality
      after Hematopoietic stem cell transplantation (HSCT). We have previously shown
      that SALL4 is a potent stimulator for the expansion of human hematopoietic
      stem/progenitor cells in vitro. In these studies, we demonstrated that systemic
      administration with TAT-SALL4B resulted in expediting auto-reconstitution and
      inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high
      dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented
      death in mice receiving lethal irradiation. Our studies also showed that TAT
      SALL4B treatment was able to enhance both the short-term and long-term
      engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was
      likely related to the in vivo expansion of donor cells in a recipient. This
      robust expansion was required for the association of SALL4B with DNA
      methyltransferase complex, an epigenetic regulator critical in maintaining HSC
      pools and in normal lineage progression. Our results may provide a useful
      strategy to enhance hematopoietic recovery and reconstitution in cord blood
      transplantation with a recombinant TAT-SALL4B fusion protein. 

PMID- 24283264
TI  - Developing practice-based evidence: benefits, challenges, and tensions.
AB  - Attempts to regulate service delivery in line with results from randomized trials
      have been vigorously debated. In this paper, results from practice-based studies
      using the CORE System illustrate the potential to enrich knowledge about the
      actual outcome of psychological therapy in routine care. These studies also
      provide data for important questions in psychotherapy research, like orientation
      differences, the importance of the therapist factor, number of sessions needed
      for clinical effect, and the alliance-outcome question. Obstacles and challenges
      in making such studies are illustrated. In conclusion, arguments are put forward
      for introducing a common measurement system that strikes a balance between
      clinicians' questions and the need for comparable data, and that encompasses the
      complexities of patients' reasons for seeking psychological help.

PMID- 24283263
TI  - Diversity of flora used for the cure of equine diseases in selected peri-urban
      areas of Punjab, Pakistan.
AB  - BACKGROUND: Plants have widely been used and documented for their therapeutic
      potential in many parts of the world. There are, however, few reports on the use
      of plants for the treatment of diseases of equines. To this end, participatory
      epidemiology and rapid rural appraisal techniques were used to document the
      plants having pharmacotherapeutic significance against different ailments of
      equines in selected population of Punjab, Pakistan. METHODS: A survey was
      conducted to interview a total of 450 respondents (150 from each of the districts
      of Faisalabad, Lahore and Sargodha of Pakistan) to collect information about
      disease recognition of the equines and their treatment on a well - structured
      questionnaire. A total of 60 plants belonging to 40 families were documented. An
      inventory was developed depicting detailed information of plants used in
      treatment of different conditions of equines. RESULTS: The top ten species of
      plants used were: Allium cepa, Zingiber officinale, Vernonia anthelmintica,
      Capsicum annum, Brassica campestris, Trachyspermum ammi, Anethum graveolens,
      Picrorhiza kurroa, Azadirachta indica, and Citrullus colocynthis. Seeds were the
      most frequently used (n = 16/60) parts, followed by leaves (n = 12/60) and fruits
      (n = 11/60) of plants. Based on the combination of different parts of plants used
      in different ratios and variation in their dose or mode of preparation led to a
      large number of recipes/remedies against wounds, lameness, bronchitis, colic,
      anorexia, dermatitis, weakness, parasitism (internal and external), fever, heat
      stress, urine retention, swelling, toxemia, and indigestion. CONCLUSIONS: This
      study generated lot of data on phytomedicinal approach for the treatment of
      ailments in the equines in some selected areas. It would, therefore, be
      imperative to expand similar studies in other parts of Pakistan and elsewhere.
      Moreover, use of the documented plants may be validated employing standard
      scientific procedures, which may have their application in the drug
      discovery/development by the pharmaceutical industry.

PMID- 24283265
TI  - MeCP2 R168X male and female mutant mice exhibit Rett-like behavioral deficits.
AB  - Rett syndrome (RTT) is a regressive developmental disorder characterized by motor
      and breathing abnormalities, anxiety, cognitive dysfunction and seizures.
      Approximately 95% of RTT cases are caused by more than 200 different mutations in
      the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). While numerous
      transgenic mice have been created modeling common mutations in MeCP2, the
      behavioral phenotype of many of these male and, especially, female mutant mice
      has not been well characterized. Thorough phenotyping of additional RTT mouse
      models will provide valuable insight into the effects of Mecp2 mutations on
      behavior and aid in the selection of appropriate models, ages, sexes and outcome
      measures for preclinical trials. In this study, we characterize the phenotype of
      male and female mice containing the early truncating MeCP2 R168X nonsense point
      mutation, one of the most common in RTT individuals, and compare the phenotypes
      to Mecp2 null mutants. Mecp2(R168X) mutants mirror many clinical features of RTT.
      Mecp2(R168X/y) males exhibit impaired motor and cognitive function and reduced
      anxiety. The behavioral phenotype is less severe and with later onset in
      Mecp2(R168X/+) females. Seizures were noted in 3.7% of Mecp2(R168X) mutant
      females. The phenotype in Mecp2(R168X/y) mutant males is remarkably similar to
      our previous characterizations of Mecp2 null males, whereas Mecp2(R168X/+)
      females exhibit a number of phenotypic differences from females heterozygous for
      a null Mecp2 mutation. This study describes a number of highly robust behavioral
      paradigms that can be used in preclinical drug trials and underscores the
      importance of including Mecp2 mutant females in preclinical studies.

PMID- 24283266
TI  - Is group cognitive behaviour therapy for postnatal depression evidence-based
      practice? A systematic review.
AB  - BACKGROUND: There is evidence that psychological therapies including cognitive
      behaviour therapy (CBT) may be effective in reducing postnatal depression (PND)
      when offered to individuals. In clinical practice, this is also implemented in a
      group therapy format, which, although not recommended in guidelines, is seen as a
      cost-effective alternative. To consider the extent to which group methods can be
      seen as evidence-based, we systematically review and synthesise the evidence for
      the efficacy of group CBT compared to currently used packages of care for women
      with PND, and we discuss further factors which may contribute to clinician
      confidence in implementing an intervention. METHODS: Seventeen electronic
      databases were searched. All full papers were read by two reviewers and a third
      reviewer was consulted in the event of a disagreement on inclusion. Selected
      studies were quality assessed, using the Cochrane Risk of Bias Tool, were data
      extracted by two reviewers using a standardised data extraction form and
      statistically synthesised where appropriate using the fixed-effect inverse
      variance method. RESULTS: Seven studies met the inclusion criteria. Meta-analyses
      showed group CBT to be effective in reducing depression compared to routine
      primary care, usual care or waiting list groups. A pooled effect size of d = 0.57
      (95% CI 0.34 to 0.80, p < 0.001) was observed at 10-13 weeks post-randomisation,
      reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non
      randomised comparisons against waiting list controls at 10-13 weeks was
      associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p <
      0.001). However due to the limitations of the available data, such as ill
      specified definitions of the CBT component of the group programmes, these results
      should be interpreted with caution. CONCLUSIONS: Although the evidence available
      is limited, group CBT was shown to be effective. We argue, therefore, that there
      is sufficient evidence to implement group CBT, conditional upon routinely
      collected outcomes being benchmarked against those obtained in trials of
      individual CBT, and with other important factors such as patient preference,
      clinical experience, and information from the local context taken into account
      when making the treatment decision.

PMID- 24283267
TI  - Keratocystic odontogenic tumour arising as a periapical lesion.
AB  - AIM: To document a case of a keratocystic odontogenic tumour (KOT) involving the
      apical region in the maxilla mimicking a periapical lesion of endodontic origin.
      SUMMARY: Benign and malignant tumours, including odontogenic lesions, can be
      erroneously diagnosed as periapical radiolucencies. KOTs mimicking periapical
      lesions of endodontic origin are uncommon, especially when the lesions involve
      the maxilla. This article describes a 55-year-old man with a well-delimited, oval
      shaped, radiolucent lesion, occupying the middle and apical third of teeth 22 and
      23. After 30 days, the clinical and radiographic findings remained unchanged and
      the patient was referred for surgical removal of the lesion. Clinical,
      radiographic and histopathological features are also discussed and compared with
      current literature.

PMID- 24283268
TI  - Everolimus is a potent inhibitor of activated hepatic stellate cell functions in
      vitro and in vivo, while demonstrating anti-angiogenic activities.
AB  - Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex
      process which involves several pathological phenomena, including hepatic stellate
      cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting
      multiple pathological processes using a single drug can be an effective choice to
      curb the progression of HCC. In the present study, we used the mTOR inhibitor
      everolimus to observe its effect on the in vitro activation of hepatic stellate
      cells and angiogenesis. The results of the present study demonstrated that
      everolimus treatment blocked the functions of the immortalized human activated
      hepatic stellate cell line LX-2 without affecting the viability and migration of
      primary human stellate cells. We also observed that treatment with everolimus (20
      nM) inhibited collagen production by activated stellate cells, as well as cell
      contraction. Everolimus treatment was also able to attenuate the activation of
      primary stellate cells to their activated form. Angiogenesis studies showed that
      everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube
      formation and migration of liver sinusoidal endothelial cells. Finally,
      everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of
      HCC. These data suggest that everolimus targets multiple mechanisms, making it a
      potent blocker of the progression of HCC from liver fibrosis.

PMID- 24283269
TI  - Assessment of an experimental rodent model of pediatric mild traumatic brain
      injury.
AB  - Childhood is one the highest risk periods for experiencing a mild traumatic brain
      injury (mTBI) from sports-related concussions, motor vehicle accidents, and
      falls. In addition, many children experience lingering symptomology (post
      concussion syndrome) from these closed head injuries. Although the negative
      sequel of mTBI has been described, a clinically reliable animal model of mild
      pediatric brain injury has not. The purpose of this study was to examine the
      validity of a modified weight-drop technique as a model for the induction of
      mTBI/concussion in juvenile rats following a single impact. Male and female rats
      (P30) were exposed to a single mTBI or a sham injury followed by a behavioral
      test battery. Juvenile rats who experienced a single mTBI displayed significant
      motor/balance impairments when tested on the beam walking task and in the open
      field, as well as deficits of executive functioning as measured with the novel
      context mismatch task and the probe trial of the Morris water task. In addition,
      both male and female rats showed depression-like behavior in the forced swim
      task, with male rats also exhibiting decreased anxiety-related behaviors in the
      elevated plus maze. The results from this study suggest that the modified weight
      drop technique induces a clinically relevant behavioral phenotype in juvenile
      rats, and may provide researchers with a reliable animal model of mTBI/concussion
      from which clinical therapeutic strategies could be developed.

PMID- 24283270
TI  - Could the Ebola virus matrix protein VP40 be a drug target?
AB  - Filoviruses are filamentous lipid-enveloped viruses and include Ebola (EBOV) and
      Marburg, which are morphologically identical but antigenically distinct. These
      viruses can be very deadly with outbreaks of EBOV having clinical fatality as
      high as 90%. In 2012 there were two separate Ebola outbreaks in the Democratic
      Republic of Congo and Uganda that resulted in 25 and 4 fatalities, respectively.
      The lack of preventive vaccines and FDA-approved therapeutics has struck fear
      that the EBOV could become a pandemic threat. The Ebola genome encodes only seven
      genes, which mediate the entry, replication, and egress of the virus from the
      host cell. The EBOV matrix protein is VP40, which is found localized under the
      lipid envelope of the virus where it bridges the viral lipid envelope and
      nucleocapsid. VP40 is effectively a peripheral protein that mediates the plasma
      membrane binding and budding of the virus prior to egress. A number of studies
      have demonstrated specific deletions or mutations of VP40 to abrogate viral
      egress but to date pharmacological inhibition of VP40 has not been demonstrated.
      This editorial highlights VP40, which is the most abundantly expressed protein of
      the virus and discusses VP40 as a potential therapeutic target. 

PMID- 24283271
TI  - Sensitivity to social and non-social threats in temperamentally shy children at
      risk for anxiety.
AB  - In the current brief report, we examined threat perception in a group of young
      children who may be at-risk for anxiety due to extreme temperamental shyness.
      Results demonstrate specific differences in the processing of social threats: 4-
      to 7-year-olds in the high-shy group demonstrated a greater bias for social
      threats (angry faces) than did a comparison group of low-shy children. This
      pattern did not hold for non-social threats like snakes: Both groups showed an
      equal bias for the detection of snakes over frogs. The results suggest that
      children who are tempermentally shy have a heightened sensitivity to social signs
      of threat early in development. These findings have implications for
      understanding mechanisms of early threat sensitivity that may predict later
      socioemotional maladjustment. 

PMID- 24283272
TI  - Processing real-world waste plastics by pyrolysis-reforming for hydrogen and high
      value carbon nanotubes.
AB  - Producing both hydrogen and high-value carbon nanotubes (CNTs) derived from waste
      plastics is reported here using a pyrolysis-reforming technology comprising a two
      stage reaction system, in the presence of steam and a Ni-Mn-Al catalyst. The
      waste plastics consisted of plastics from a motor oil container (MOC), commercial
      waste high density polyethylene (HDPE) and regranulated HDPE waste containing
      polyvinyl chloride (PVC). The results show that hydrogen can be produced from the
      pyrolysis-reforming process, but also carbon nanotubes are formed on the
      catalyst. However, the content of 0.3 wt.% polyvinyl chloride in the waste HDPE
      (HDPE/PVC) has been shown to poison the catalyst and significantly reduce the
      quantity and purity of CNTs. The presence of sulfur has shown less influence on
      the production of CNTs in terms of quantity and CNT morphologies. Around 94.4
      mmol H2 g(-1) plastic was obtained for the pyrolysis-reforming of HDPE waste in
      the presence of the Ni-Mn-Al catalyst and steam at a reforming temperature of 800
      degrees C. The addition of steam in the process results in an increase of
      hydrogen production and reduction of carbon yield; in addition, the defects of
      CNTs, for example, edge dislocations were found to be increased with the
      introduction of steam (from Raman analysis). 

PMID- 24283273
TI  - Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of
      the breast.
AB  - Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity
      added by WHO in 2003. Since then, studies have indicated that NCB potentially
      displays a worse prognosis than invasive ductal carcinoma. However, due to a lack
      of standard use of immunohistochemical staining for neuroendocrine markers and
      the fact that NCB may only show slight neuroendocrine morphology that can easily
      be overlooked, NCB is often underdiagnosed. Consequently, there is a need for
      fast and reliable detection method for NCB. Here, we take a first step toward
      finding an easy way of identifying NCB by investigating the usefulness of tissue
      microarray (TMA) analysis as a screening tool. We present our findings with
      regard to sensitivity and specificity compared with whole-mount sections. The
      material consists of 240 cases of breast cancer divided into 20 TMA blocks that
      were all immunohistochemically stained for the neuroendocrine markers
      chromogranin A and synaptophysin. Cases positive in more than 50% of the tumor
      cells were accepted in accordance with WHO (2003) standards of NCB. Sensitivity
      and specificity for TMA sections vs whole-mount sections were found to be 100%
      and 97.8%, respectively, suggesting that TMA analysis is a reliable method for
      NCB detection.

PMID- 24283274
TI  - Correspondence of high-frequency ultrasound and histomorphometry of healing
      rabbit Achilles tendon tissue.
AB  - OBJECTIVES: Static and dynamic high-frequency ultrasound of healing rabbit
      Achilles tendons were set in relationship to histomorphometric analyses at three
      and six weeks post-surgery. MATERIALS AND METHODS: Twelve New Zealand White
      rabbits received a clean-cut Achilles tendon laceration (the medial and lateral
      Musculus gastrocnemius) and were repaired with a four-strand Becker suture. Six
      rabbits got additionally a tight polyester urethane tube at the repair site in
      order to vary the adhesion extent. Tendons were analysed by static and dynamic
      ultrasound (control: healthy contralateral legs). The ultrasound outcome was
      corresponded to the tendon shape, tenocyte and tenoblast density, tenocyte and
      tenoblast nuclei width, collagen fibre orientation and adhesion extent. RESULTS:
      The spindle-like morphology of healing tendons (ultrasound) was confirmed by the
      swollen epitenon (histology). Prediction of adhesion formation by dynamic
      ultrasound assessment was confirmed by histology (contact region to surrounding
      tissue). Hyperechogenic areas corresponded to acellular zones with aligned fibres
      and hypoechogenic zones to not yet oriented fibres and to cell-rich areas.
      CONCLUSIONS: These findings add new in-depth structural knowledge to the
      established non-invasive analytical tool, ultrasound.

PMID- 24283275
TI  - Aralia cordata inhibits triacylglycerol biosynthesis in HepG2 cells.
AB  - Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in
      triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as
      one of the drug targets for treating hepatic steatosis, insulin resistance, and
      other metabolic disorders. The aim of this study was to investigate the GPAT
      inhibitors from natural products and to evaluate their effects. The methanol
      extract of Aralia cordata roots showed a strong inhibitory effect on the human
      GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent
      pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata,
      which suppressed the GPAT1 activity with IC50 value of 60.5 MUM. PA markedly
      reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT
      activity and therefore significantly decreased synthesis of TAG in the HepG2
      cells. These results suggest that PA as well as A. cordata root extract could be
      beneficial in controlling lipid metabolism.

PMID- 24283277
TI  - Myrciaria cauliflora peel flour had a hypolipidemic effect in rats fed a
      moderately high-fat diet.
AB  - The aim of this study was to evaluate the hypolipidemic effects of Myrciaria
      cauliflora peel flour (MPF) in rats. Previously, it was determined the proximate
      composition, total phenolics, and anthocyanins of MPF. Then, groups of male rats
      were randomly assigned to one of the five treatment groups. The standard group
      received a basal diet as recommended by the American Institute of Nutrition
      (AIN93M). The control group (CTRL) received the AIN93M diet, which added 7% of
      pork lard. The jaboticaba groups had their diets similar to CTRL, but added MPF
      at 7 (JAB1), 10 (JAB2), or 15% (JAB3). Serum and liver cholesterol as well as
      serum levels of high-density lipoprotein (HDL), triglycerides (TG), and glucose
      were evaluated. Fecal output of lipids was also measured. MPF had expressive
      amounts of fibers (25.28+/-2.52 g/100 g), total phenolics (18.95+/-5.27 mg/100
      g), and anthocyanins (6.82+/-0.18 mg/100 g). The inclusion of the MPF at three
      ratios, reduced serum cholesterol and TG compared with CTRL. JAB3 raised serum
      HDL and reduced liver cholesterol compared with CTRL. JAB3 and JAB2 reduced serum
      glucose compared with CTRL. JAB groups eliminated more feces and had pH values
      lower than CTRL. However, there was no difference in lipid fecal output between
      all groups. MPF has a hypolipidemic potential, especially on reducing serum
      cholesterol and TG. These effects can be attributed, at least in part, to its
      fiber and phenolic composition.

PMID- 24283276
TI  - Postprandial glucose and NF-kappaB responses are regulated differently by
      monounsaturated fatty acid and dietary fiber in impaired fasting glucose
      subjects.
AB  - Recently, much attention has been paid to observational studies that have linked
      postprandial glycemic response with the risk of cardiovascular disease. In this
      study, we investigated whether the nutrient composition of dietary formula might
      affect the postprandial inflammation in impaired fasting glucose (IFG) subjects.
      Eight subjects underwent three trials in a double-blind, randomized, crossover
      study with a 1-week washout period. The subjects were given three formulas
      according to serving size: (1) high-fiber formula (FF); (2) high-monounsaturated
      fatty acid formula (MF); and (3) control formula (CF). The area under the curves
      (AUCs) for glucose decreased 0.65- and 0.54-fold in the FF and MF trials,
      respectively, when compared with CF. A similar pattern was observed for the
      postprandial insulin response. However, as observed by the phosphorylation of
      proteolytic degradation product IkappaB, the AUC for activation of nuclear
      transcription factor kappaB (NF-kappaB) in peripheral blood mononuclear cells was
      significantly decreased in the FF trial, but not with MF (P=.0114). These
      findings demonstrated that postprandial glucose and inflammatory responses might
      be regulated differently by the nutrient composition of dietary formulas in IFG
      subjects.

PMID- 24283278
TI  - Caring for children's developing mouths. Foreword.

PMID- 24283279
TI  - The primary and mixed dentition, post-eruptive enamel maturation and dental
      caries: a review.
AB  - The mouth is in flux from the time the primary teeth begin to erupt, in the first
      year of life, through to the end of the 'mixed dentition' (i.e. the concurrent
      eruption of the permanent teeth and exfoliation of the primary teeth), at around
      12 years of age. Primary teeth facilitate the development of the facial muscles
      and speech. They act as 'guides' for erupting permanent teeth. If lost
      prematurely, subsequent misalignment of permanent teeth can make them difficult
      to clean and possibly more caries-prone. During the mixed dentition phase, teeth
      are at relatively high risk of caries. Erupting teeth are difficult to clean and
      cleaning may be avoided because of tender gums and behavioural factors in
      children. Permanent enamel (and possibly primary enamel) undergoes post-eruptive
      maturation, accumulating fluoride, becoming harder, less porous and less caries
      prone. Overall, primary teeth are more vulnerable to caries than permanent teeth.
      Widespread use of fluoride toothpaste has effected marked reductions in caries.
      Some evidence exists that fluoride delivered from toothpastes may be somewhat
      more effective in reducing caries in primary than in permanent teeth. However,
      caries remains a public health concern globally. New fluoride toothpaste
      formulations, optimised using in vivo fluoride delivery and efficacy studies, may
      improve the caries resistance of mineral deposited during post-eruptive
      maturation. Behaviour should not be ignored; new formulations will be more
      effective if used according to professionally endorsed recommendations based on
      sound science. Establishing good oral hygiene behaviour early in life can lead to
      lasting anti-caries benefits. 

PMID- 24283280
TI  - The effect of dentifrice quantity and toothbrushing behaviour on oral delivery
      and retention of fluoride in vivo.
AB  - While toothpaste F(-) concentration and rinsing regimen have well-characterised
      impacts on fluoride's effectiveness, other aspects of brushing regimen have much
      less well-established effects, in particular, dentifrice quantity and brushing
      duration. An in vivo study (n = 42) of oral fluoride delivery (i.e. oral
      disposition post-brushing), and retention (i.e. concentration of F(-) in saliva
      post-brushing, a known efficacy predictor), was performed to compare effects
      observed with those of dentifrice F(-) concentration and rinsing regimen.
      Subjects brushed with a NaF-silica dentifrice (Aquafresh Advanced, 1,150 ppm F(-)
      ) or a control dentifrice (250 ppm F(-) , same base), for 45, 60, 120 or 180
      seconds with 0.5 or 1.5 g dentifrice, and rinsed with 15 ml water once or three
      times in a cross-over design. The F(-) concentration was measured in post
      brushing expectorate, rinse and toothbrush washing samples, and in saliva between
      5-120 minutes after brushing. Using 1.5 g versus 0.5 g dentifrice increased F(-)
      in all samples: oral retention of F(-) was almost doubled by this increase.
      Increasing duration of brushing had more complex effects. The amount of F(-) in
      the expectorate increased but decreased in both rinse and toothbrush washing
      samples. Oral F(-) retention increased, but only in the period 30-120 minutes
      after brushing. Over the ranges investigated, the order of importance on oral F(
      ) retention was: dentifrice F(-) concentration > quantity > rinsing regimen >
      brushing duration. Hence, increasing dentifrice quantity and, to a lesser extent,
      the duration of brushing, can elevate oral fluoride post-brushing. Evidence is
      accumulating that the importance of these variables to fluoride efficacy may have
      been underestimated.

PMID- 24283281
TI  - How much is a 'pea-sized amount'? A study of dentifrice dosing by parents in
      three countries.
AB  - To provide optimal fluoride effectiveness against caries while minimising risk of
      negative effects from excessive ingestion from toothbrushing, the fluoride dose
      delivered at each occasion is critical. This is particularly important for young
      children, so using a 'pea-sized amount' is generally recommended. However, there
      appears little guidance regarding what this means in practice, although it has
      been indicated to be 0.25 g. This study investigated, using conventional
      toothpastes and toothbrushes in Germany, the USA and the UK, how much toothpaste
      parents dispense for their 3- to 6 year-old children, and their interpretation of
      a 'pea-sized' amount of toothpaste. When asked to dispense the amount they would
      normally for their child, the majority of parents dosed substantially more than
      0.25 g; in Germany, all parents over-dispensed. The amount dispensed varied
      widely: those parents at the 75th centile dispensed approximately twice the
      amount dispensed by those at the 25th centile, irrespective of country. When
      asked to dispense a pea-sized amount, the mean amount dosed decreased
      significantly in all countries. In the USA, electric toothbrush users dispensed
      about 0.1 g more than manual toothbrush users. While over-dispensing of fluoride
      toothpaste remains a cause for concern, it may be argued that the general
      recommendation to use a pea-sized amount of toothpaste generally works well in
      practice to balance the conflicting demands of risk and benefit from
      toothbrushing with fluoride toothpaste in young children.

PMID- 24283282
TI  - A randomised clinical study to evaluate experimental children's toothpastes in an
      in-situ palatal caries model in children aged 11-14 years.
AB  - OBJECTIVES: To compare three children's sodium fluoride toothpastes to placebo
      with respect to enamel remineralisation potential, enamel fluoride uptake and net
      acid resistance using an in situ palatal caries model in children aged 11-14
      years following a single brushing. DESIGN: This was a randomised, single blind
      (laboratory analyst), single-centre, four-treatment, crossover study with a 7-day
      washout period between treatments. The treatments were 1,426 ppm fluoride, 1,000
      ppm fluoride, 500 ppm fluoride and 0 ppm fluoride (placebo) toothpaste
      (NaF/silica). A custom made in situ palatal appliance was used by each subject in
      all treatment periods. At each of the four treatment visits subjects wore the
      appliance containing four partially demineralised human enamel specimens for 5
      minutes and then brushed their teeth using a standardised procedure for 60
      seconds under supervision using 1.0 g (+/-0.1 g) of their assigned toothpaste.
      After 4 hours the appliance was removed and enamel specimen recovered. This
      process was repeated until all subjects completed all four study treatment
      visits. Recovered enamel specimens were analysed for per cent surface
      microhardness recovery (%SMHR; Knoop) and enamel fluoride uptake (EFU; microdrill
      biopsy). Subsequently, specimens were demineralised in vitro to determine their %
      net acid resistance (%NAR; Knoop). RESULTS: All three fluoride toothpastes
      demonstrated significantly greater %SMHR, EFU and %NAR compared with 0 ppm F
      toothpaste. The model demonstrated a dose response over the range 0 to 1,426 ppm
      fluoride for %SMHR, EFU and %NAR. There was no significant difference between 500
      ppm F and 1,000 ppm F for %SMHR and between 1,000 ppm F and 1,426 ppm F for
      %SMHR, EFU and %NAR. CONCLUSIONS: The present in situ study demonstrated that the
      children's fluoride toothpastes tested are capable of delivering cariostatic
      amounts of fluoride to early caries lesions following a single brushing.

PMID- 24283283
TI  - A randomised clinical study to evaluate the effect of brushing duration on
      fluoride levels in dental biofilm fluid and saliva in children aged 4-5 years.
AB  - OBJECTIVES: To compare the effect of 40 seconds versus 2 minutes brushing on
      saliva and dental biofilm fluid fluoride in children ages 4-5 years over 1 hour.
      DESIGN: This was a single-blind, cross-over, randomised, two-period clinical
      study in healthy children. Three days before the start of each treatment subjects
      received a thorough brushing and then refrained from all oral hygiene procedures.
      At treatment visits, after collecting baseline biofilm and saliva samples, staff
      brushed the occlusal surfaces of the subject's posterior teeth with a pea-sized
      amount (0.25 g) of NaF/silica toothpaste for the randomised time. Samples were
      taken at 5 minutes, 15 minutes, 30 minutes and 60 minutes after brushing and
      analysed for fluoride using a microanalytical methodology. There was a minimum 4
      day washout period between treatments. RESULTS: Log changes from baseline biofilm
      fluid and saliva fluoride were statistically significant (P < 0.05) for both
      brushing times at all post-brushing time-points [except 60 minutes saliva where P
      = 0.06 (t-test)]. Statistically significantly greater ln-AUC (area under the
      curve) was found for biofilm fluid and salivary fluoride after brushing for 2
      minutes compared with brushing for 40 seconds over the 1-hour test period. There
      was a statistically significantly higher concentration of fluoride in the log
      change from baseline saliva levels after 5, 15, 30 and 60 minutes for the 2
      minute brushing time compared with 40 seconds brushing time. There was no
      statistically significant difference in concentration of log change from baseline
      fluoride levels in biofilm fluid at each individual time-point (5, 15, 30 and 60
      minutes) for the 2-minute brushing time compared with the 40-second brushing
      time, but significant differences were observed for 15, 30 and 60 minutes in
      favour of 2-minute brushing time when log biofilm fluid value was analysed.
      CONCLUSION: The findings provide further evidence for the benefits of increased
      duration of brushing with respect to fluoride delivery.

PMID- 24283284
TI  - In vitro assessment of a toothpaste range specifically designed for children.
AB  - OBJECTIVE: To evaluate the ability of a range of low abrasivity experimental
      toothpastes designed for use by children at different stages of their development
      (typically ages 0-2 years, 3-5 years and 6+ years) to promote fluoride uptake and
      remineralisation of artificial caries lesions. METHODS: pH cycling study:
      demineralised human permanent enamel specimens were subjected to a daily pH
      cycling regime consisting of four 1-minute treatments with toothpaste slurries, a
      4-hour acid challenge and remineralisation in pooled whole human saliva. Surface
      microhardness (SMH) was measured at baseline, 10 days and 20 days, and the
      fluoride content determined at 20 days. Enamel Fluoride Uptake (EFU): these
      studies were based on Method #40 described in the US Food and Drug Administration
      (FDA) testing procedures. Abrasivity: relative enamel abrasivity (REA) and
      relative dentine abrasivity (RDA) were measured using the Hefferren abrasivity
      test. Bioavailable fluoride: the bioavailable fluoride was determined for all
      experimental toothpastes from slurries of one part toothpaste plus 10 parts
      deionised water. RESULTS: Enamel remineralisation measured by changes in SMH
      correlated with enamel fluoride content. A statistically significant fluoride
      dose response was observed for all toothpastes tested across all age groups (P <
      0.05). The fluoride content of specimens in the pH cycling model correlated with
      the EFU testing results. The enamel and dentine abrasivities were low and the
      level of bioavailable fluoride was high for all experimental toothpastes.
      CONCLUSION: A series of low abrasivity experimental toothpastes were developed
      which were effective at promoting fluoride uptake and remineralisation of
      artificial caries lesions.

PMID- 24283286
TI  - Diet and the microbial aetiology of dental caries: new paradigms.
AB  - The microbial and dietary factors that drive caries have been studied
      scientifically for 120 years. Frequent and/or excessive sugar (especially
      sucrose) consumption has been ascribed a central role in caries causation, while
      Streptococcus mutans appeared to play the key role in metabolising sucrose to
      produce lactic acid, which can demineralise enamel. Many authors described caries
      as a transmissible infectious disease. However, more recent data have shifted
      these paradigms. Streptococcus mutans does not fulfil Koch's postulates -
      presence of the organism leading to disease, and absence of the organism
      precluding disease. Furthermore, molecular microbiological methods have shown
      that, even with a sugar-rich diet, a much broader spectrum of acidogenic microbes
      is found in dental plaque. While simple sugars can be cariogenic, cooked starches
      are also now recognised to be a caries threat, especially because such starches,
      while not 'sticky in the hand', can be highly retentive in the mouth. Metabolism
      of starch particles can yield a prolonged acidic challenge, especially at
      retentive, caries-prone sites. These changes in the paradigms of caries aetiology
      have important implications for caries control strategies. Preventing the
      transmission of S. mutans will likely be inadequate to prevent caries if a
      sufficiently carbohydrate-rich diet continues. Similarly, restriction of sucrose
      intake, although welcome, would be unlikely to be a panacea for caries,
      especially if frequent starch intake persisted. Instead, approaches to optimise
      fluoride delivery, to target plaque acidogenicity or acidogenic microbes, to
      promote plaque alkali generation, to increase salivary flow or replace
      fermentable carbohydrates with non-fermentable alternatives may be more
      promising.

PMID- 24283285
TI  - Important considerations in the development of toothpaste formulations for
      children.
AB  - A number of factors should be taken into account when designing toothpaste
      formulations for use by children at the different stages of their development.
      While adult toothpaste formulations may provide caries prevention benefits for
      children at risk of caries, these formulations may also contain higher levels of
      abrasive in order to address the staining needs of the adult population owing to
      smoking and the consumption of dietary chromogens such as coffee and tea, which
      are not normally found in the diet of children. While toothpastes formulated for
      adults are also likely to contain higher concentrations of surfactant and
      flavour, many children prefer toothpastes with mild flavours and modest foaming
      characteristics. An ideal children's toothpaste formulation should therefore aim
      to maximise fluoride availability, with appropriate abrasivity, while still
      delivering effective cleaning, as well as levels and types of flavour and
      surfactant to provide an acceptable brushing experience. Selection of toothpaste
      flavour types for children of different ages should ideally be based directly
      upon preference data from children. Flavours perceived as pleasant during
      brushing studies have been linked to increased brushing time, which, in turn, can
      increase the delivery and efficacy of fluoride from toothpastes. Therefore,
      manufacturers select tested, child-friendly flavours to maximise compliance,
      providing a more pleasurable brushing experience and oral health benefits. 

PMID- 24283287
TI  - Associations between Mycobacterium avium subsp. paratuberculosis antibodies in
      bulk tank milk, season of sampling and protocols for managing infected cows.
AB  - BACKGROUND: The objective of this study was to identify associations between the
      concentration of Mycobacterium avium subsp. paratuberculosis (MAP) antibodies in
      bulk milk and potential risk factors in herd management and herd characteristics,
      explaining high MAP antibody titers in milk. An extensive questionnaire was
      administered to 292 organic and conventional dairy farms from New York, Wisconsin
      and Oregon. Bulk milk samples were taken from each farm for MAP enzyme-linked
      immunosorbent assay (ELISA). A general linear model was constructed with MAP
      ELISA value as the outcome variable and the management factors and herd
      characteristics as independent variables, while at the same time controlling for
      the study design variables of state, herd size, and production system (organic or
      conventional). High bulk tank MAP ELISA value may be due to either a high
      prevalence of MAP in a herd with many cows contributing to the antibody titer or
      due to a few infected cows that produce large quantities of antibodies. RESULTS:
      Results of the regression models indicated that bulk milk ELISA value was
      associated with season of sampling and the presence or absence of protocols for
      managing MAP-positive cows. The concentration of MAP antibodies in bulk milk
      varied seasonally with a peak in the summer and low concentrations in the winter
      months. When compared to farms that had never observed clinical Johne's disease,
      keeping MAP-positive cows or only culling them after a period of delay was
      associated with an increase in optical density. CONCLUSIONS: The seasonal
      variation in MAP antibody titers, with a peak in the summer, may be due to a
      seasonal increase in MAP-bacterial load. Additionally, seasonal calving practices
      may contribute to seasonal fluctuations in MAP antibody titers in bulk tank milk.
      Keeping MAP-positive cows increases the antibody titer in bulk milk, likely due
      to direct antibody production in the infected cow and indirect triggering of
      antibody production in herdmates.

PMID- 24283288
TI  - Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic
      photosensitizer.
AB  - Polymer vesicles formed by a pair of oppositely charged poly(ethylene glycol)
      (PEG)-based block aniomer and homocatiomer, termed "PICsomes", have tunable size,
      and are characterized by unique semipermeable property due to the flexible and
      tunable hydrophilicity of polyion complex (PIC) membranes. The PICsomes can
      encapsulate a variety of molecules in an inner aqueous phase just by a simple
      vortex mixing of solution, expecting their utility as nanocontainers of
      substances with biomedical interests. Here, we report on a new functionality of
      the PICsomes: photoinduced release of photoactive agents for intracellular drug
      delivery. A potent photosensitizer, Al(III) phthalocyanine chloride disulfonic
      acid (AlPcS2a), was efficiently incorporated into the PICsomes (11%(w/w)), and
      its quick release was induced by photoirradiation possibly due to the
      photochemical damage of the PIC membranes. The combination of a high-resolution
      fluorescent confocal microscopy and a lysosome membrane-specific staining method
      revealed that such photoinduced release of AlPcS2a occurred even in the lysosomes
      of living cells after endocytic internalization. Simultaneously, the released
      AlPcS2a photochemically affected the integrity of the lysosomal membranes,
      leading to the translocation of AlPcS2a and PICsomes themselves to the cytoplasm.
      Consequently, the AlPcS2a-encapsulated PICsomes (AlPcS2a-PICsomes) exhibited
      appreciably stronger photocytotoxicity compared with free AlPcS2a alone. Thus,
      the AlPcS2a-PICsomes have promising feasibility for the photodynamic therapy or
      the photoinduced cytoplasmic delivery of therapeutic molecules. 

PMID- 24283289
TI  - High-throughput deep sequencing shows that microRNAs play important roles in
      switchgrass responses to drought and salinity stress.
AB  - MicroRNAs (miRNAs) are an important class of small regulatory RNAs. The goal of
      this study was to analyse stress-responsive miRNAs in switchgrass (Panicum
      virgatum), the emerging biofuel crop, to facilitate choosing gene targets for
      improving biomass and biofuel yield. After sequencing three small RNA libraries
      constructed from control, salt- and drought-treated switchgrass using Illumina
      sequencing technology, we identified 670 known miRNA families from a total of
      more than 50 million short reads. A total of 273 miRNAs were identified with
      precursors: 126 conserved miRNAs and 147 novel miRNAs. Of them, 265 miRNAs were
      found to have their opposite sequences (miRNA*) with 2-nt overhang on the 3' end.
      Of them, 194 were detected in switchgrass transcriptome sequences generated from
      31 high-throughput RNA sequencing (RNA-Seq) data sets in NCBI. Many miRNAs were
      differentially or uniquely expressed during salinity or drought stress treatment.
      We also discovered 11 miRNA clusters containing 29 miRNAs. These identified
      miRNAs potentially targeted 28549 genes with a various function, including
      transcription factors, stress-response proteins and cellulose biosynthesis
      related proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) analysis showed that the identified miRNAs and their targets were
      classified to 3779 GO terms including 1534 molecular functions, 1851 biological
      processes and 394 cellular components and were enriched to 147 KEGG pathways.
      Interestingly, 195 miRNA families and 450 targets were involved in the
      biosynthesis pathways of carbon, glucose, starch, fatty acid and lignin and in
      xylem formation, which could aid in designing next-generation switchgrass for
      biomass and biofuel.

PMID- 24283290
TI  - Estrogen receptor alpha mediates proliferation of breast cancer MCF-7 cells via a
      p21/PCNA/E2F1-dependent pathway.
AB  - High expression of estrogen receptor alpha (ERalpha) is associated with a poor
      prognosis that correlates closely with cellular proliferation in breast cancer.
      However, the exact molecular mechanism by which ERalpha controls breast cancer
      cell proliferation is not clear. Here we report that ERalpha regulates the cell
      cycle by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen
      (PCNA) and proliferation-related Ki-67 antigen (Ki-67) to promote proliferation
      of MCF-7 cells. In addition, 17-beta-estradiol (E2) enhances ERalpha-induced
      proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67.
      Knockdown of ERalpha significantly affects PCNA/Ki-67 and p53/p21 expression.
      Furthermore, ERalpha inhibits the transcriptional activity of p53/p21 in an
      estrogen response element-dependent manner. More importantly, we provide new
      evidence that ERalpha mediates proliferation of MCF-7 cells by up-regulating miR
      17 to silence the expression of p21. Thus, these data provide new insights into
      the underlying effect of ERalpha on breast cancer proliferation.

PMID- 24283291
TI  - Fears of happiness and compassion in relationship with depression, alexithymia,
      and attachment security in a depressed sample.
AB  - OBJECTIVES: In a non-clinical population, fears of compassion and fear of
      happiness have both been found to be highly correlated with alexithymia and
      depression. This study sought to explore these processes and their links with
      adult attachment and social safeness and pleasure in a depressed group. METHOD: A
      total of 52 participants suffering from moderate to severe depression completed
      measures of fears of happiness, compassion from others and for self, in addition
      to measures of alexithymia, attachment, social safeness, and depression, anxiety,
      and stress. RESULTS: Fears of compassion and happiness were highly correlated
      with alexithymia, adult attachment, and depression, anxiety, and stress. Fear of
      happiness was found to be the best predictor of depression, anxiety, and stress,
      whereas fear of compassion from others was the best predictor of adult
      attachment. A path analysis showed that fears of positive emotion fully mediate
      the link between alexithymia and depression. This clinical sample had higher mean
      scores in fears of positive emotions, alexithymia, and depression, anxiety, and
      stress than a previously studied student sample. CONCLUSIONS: This study adds to
      the evidence that fears of positive emotions are important features of mental
      health difficulties. Unaddressed, these fears can block positive emotions and may
      lead to emotional avoidance of positive affect thus contributing as blocks to
      successful therapy. Therapies for depression may therefore profitably assess and
      desensitize the fear of positive emotions.

PMID- 24283292
TI  - Therapists' thoughts on therapy: clinicians' perceptions of the therapy processes
      that distinguish schema, cognitive behavioural and psychodynamic approaches.
AB  - OBJECTIVE: Debates continue over shared factors in therapy processes between
      different theoretical orientations. By seeking the opinions of practicing
      clinicians, this study aimed to elucidate the similarities and differences
      between cognitive-behavioural (CBT), psychodynamic (PDT), and schema therapy (ST)
      approaches. METHOD: Forty-eight practitioners aligning with one of the three
      approaches were asked to identify crucial processes in their therapy using a
      modified online version of the Psychotherapy Process Q-set. RESULTS: Distinct
      differences between each theoretical orientation with few shared common factors
      were found. A comparison with ratings from previous studies indicated that CBT
      therapists have not changed over the last 20 years, whereas PDT therapists have
      changed and the differences appeared consistent with modern PDT theory.
      CONCLUSIONS: The differences between the therapy approaches were consistent with
      theories underlying each model. PDT therapists valued a neutral relationship, CBT
      therapists emphasized a didactic interaction, and therapists form a ST
      orientation placed a greater emphasis on emotional involvement.

PMID- 24283293
TI  - Nutritional status of children under 5 years of age in the Brazilian Western
      Amazon before and after the Interoceanic highway paving: a population-based
      study.
AB  - BACKGROUND: The aim of this study was to analyse the prevalence of
      undernutrition, overweight and associated factors, before and after the
      implementation of the Interoceanic Highway. METHODS: A population-based cross
      sectional study on children under 5 years of age was conducted in the
      municipality of Assis Brasil, AC, Brazil, in 2003 and 2010. Prevalence of
      undernutrition was observed by using height-for-age Z-scores (HAZ) and adopting a
      cut-off point equal to or lower than a -2 Z-score. Overweight prevalence was
      defined by a cut-off point equal to or greater than a +2 Z-score of the WHZ
      index. Z-scores were calculated relative to WHO 2006 reference data. Semi
      structured questionnaires were applied to the children's guardians, investigating
      family socio-economic and demographic characteristics, morbidities, access to
      services and child care. Associated factors were identified by hierarchical
      multiple logistic regression analysis. RESULTS: The prevalence of low HAZ
      (undernutrition) was 7.0% in 2003 and 12.2% in 2010. The prevalence of high WHZ
      (overweight) was 1.0% and 6.6% for 2003 and 2010, respectively. It was not
      possible to adjust the multiple model for the year 2003. The factors associated
      with low HAZ in 2010 were: wealth index, the situation of living with biological
      parents, maternal height and presence of open sewage, whereas the factors
      associated with a high WHZ in the same year were: child's age, mother's time of
      residence in the location, mother's body mass index. CONCLUSIONS: Overweight
      increase within this undernutrition scenario reveals that the process of
      nutritional transition began in this Amazonian city only in the last decade, and
      therefore, it is delayed when compared to overweight in other parts of Brazil.
      Such nutritional transition in Assis Brasil may have been facilitated by the
      construction of the Interoceanic Highway.

PMID- 24283294
TI  - Clarifying misconceptions about compassionate care.
AB  - AIM: To discuss the meaning of compassionate care as it applies to staff,
      patients and families in health and social care settings, its application to
      practice and how organizational infrastructures affect the delivery of care.
      BACKGROUND: The term compassion has assumed headline status and inclusion in
      current health and social care policy. Clarity of what the term means in practice
      is needed and may help to promote delivery of compassionate care consistently
      across health and social care settings. DESIGN: Discussion paper. DATA SOURCES:
      This article draws on data from an action research programme (Leadership in
      Compassionate Care Programme, 2007-2011) that focused on embedding compassionate
      care into practice and education and related literature focused on compassionate
      person-centred care. A literature search was conducted and articles published in
      English relating to the terms compassionate, person-centred care between 1999
      2011 were included. DISCUSSION: Perceptions of compassion, practising compassion
      and the infrastructure to support compassion are discussed. IMPLICATIONS FOR
      NURSING: It is anticipated that this discussion will prompt further debate, raise
      awareness and help to clarify the meaning of compassion in everyday practice with
      patients, relatives and staff, so that it can be more clearly named, valued and
      defended. CONCLUSION: This article challenges some of the beliefs and values that
      underpin the meaning of compassionate care and its application to practice. It
      brings greater clarity to the meaning of compassion, which could be used to form
      the basis of shared visions of caring, both strategic and operational, across
      organizations.

PMID- 24283295
TI  - Conformational control in the population of the triplet state and photoreactivity
      of nitronaphthalene derivatives.
AB  - Nitronaphthalene derivatives (NNDs) are among the most abundant volatile nitro
      polycyclic aromatic hydrocarbons found in the Earth's atmosphere. Investigations
      of the atmospheric degradation processes show that photolysis is the major
      degradation pathway under ambient conditions. In this contribution, we present
      photochemical measurements and quantum-chemical calculations of three major NNDs.
      It is shown that the magnitude of the photodegradation and triplet quantum yields
      in 1-nitronaphthalene (1NN), 2-methyl-1-nitronaphthalene (2M1NN), and 2
      nitronaphthalene (2NN) are inversely related to each other. In accord with a
      recent time-resolved and computation study (J. Phys. Chem. A 2013, 117, 6580) and
      in order to explain this striking observation we propose that these photochemical
      yields are largely controlled by (1) the conformational heterogeneity of the
      nitro-aromatic torsion angle, (2) the energy gap (spin-orbit coupling
      interaction) between the excited singlet state and the receiver triplet state,
      and (3) the topology of the excited singlet state in the Franck-Condon region of
      configuration space sampled at the time of excitation. A distribution of torsion
      angles closer to 90 degrees  leads to a higher photoreactivity. Methylation of
      the ortho position in 1NN to give 2M1NN increases the photoreactivity by 97%,
      while 2NN is largely photoinert. Conversely, the triplet yield decreases as the
      distribution of torsion angles gets closer to 90 degrees : 0.93 +/- 0.15 in 2NN,
      0.64 +/- 0.12 in 1NN, and 0.33 +/- 0.05 in 2M1NN. These results suggest an
      important relationship between conformational heterogeneity and the photochemical
      fate of these NNDs. This structure-photoreactivity relationship is of relevance
      to current efforts aimed at modeling and understanding the distribution patterns
      of NNDs in the atmosphere and their overall contribution to air quality. 

PMID- 24283296
TI  - Measuring risk-taking in mice: balancing the risk between seeking reward and
      danger.
AB  - Assessing risk is an essential part of human behaviour and may be disrupted in a
      number of psychiatric conditions. Currently, in many animal experimental designs
      the basis of the potential 'risk' is loss or attenuation of reward, which fail to
      capture 'real-life' risky situations where there is a trade-off between a
      separate cost and reward. The development of rodent tasks where two separate and
      conflicting factors are traded against each other has begun to address this
      discrepancy. Here, we discuss the merits of these risk-taking tasks and describe
      the development of a novel test for mice - the 'predator-odour risk-taking' task.
      This paradigm encapsulates a naturalistic approach to measuring risk-taking
      behaviour where mice have to balance the benefit of gaining a food reward with
      the cost of exposure to a predator odour using a range of different odours (rat,
      cat and fox). We show that the 'predator-odour risk-taking' task was sensitive to
      the trade-off between cost and benefit by demonstrating reduced motivation to
      collect food reward in the presence of these different predator odours in two
      strains of mice and, also, if the value of the food reward was reduced. The
      'predator-odour risk-taking' task therefore provides a strong platform for the
      investigation of the genetic substrates of risk-taking behaviour using mouse
      models, and adds a further dimension to other recently developed rodent tests.

PMID- 24283297
TI  - QTL mapping reveals a tight linkage between QTLs for grain weight and panicle
      spikelet number in rice.
AB  - BACKGROUND: A number of QTL studies reported that one genomic region was
      associated with several traits, indicating linkage and/or pleiotropic effects.
      The question of pleiotropy versus tight linkage in these studies should be solved
      using a large-size population combined with high-density mapping. For example, if
      each of the 2 parents has a TGW-increasing or SPP-increasing QTL that is tightly
      linked, complementary combination of the 2 beneficial QTLs by using molecular
      markers could produce higher yields compared to the 2 parents. However, a
      pleiotropic QTL with opposite effects on the SPP and 1,000-grain weight (TGW) is
      complicated and challenging in terms of its application to rice improvement.
      RESULTS: In this study, using a series of BC5F4 nearly isogenic lines (NILs) that
      were derived from a cross between the Korean japonica cultivar Hwayeongbyeo and
      Oryza rufipogon, we demonstrated that 2 QTLs, qSPP5 for spikelets per panicle
      (SPP) and qTGW5 for grain weight (TGW), are tightly linked on chromosome 5.
      Alleles from the O. rufipogon parent increased the SPP and decreased TGW in the
      Hwayeongbyeo background. qSPP5 was located within a 803-kb interval between the
      simple sequence repeat (SSR) markers INDEL3 and RM18076. Based on the map
      position, qTGW5 seemed to be the same gene as qSW5, which controls grain
      morphology. The additive effect of the O. rufipogon allele at qSPP5 was 10-15
      SPP, and 33.0% of the phenotypic variance could be explained by the segregation
      of the SSR marker RM18058. Yield trials with BC5F4 NILs showed that lines that
      contained a homozygous O. rufipogon introgression at the qSPP5 region out-yielded
      sibling NILs that contained Hwayeongbyeo DNA by 15.3% and out-yielded the
      Hwayeongbyeo parent by 7.3%. CONCLUSION: Based on the finding that the O.
      rufipogon allele for the SPP was beneficial in the japonica and indica cultivar
      backgrounds, the qSPP5 allele could be valuable for improving rice yields. In
      addition, the NIL populations and molecular markers are useful for cloning qSPP5.

PMID- 24283298
TI  - Indoor exposure to toluene from printed matter matters: complementary views from
      life cycle assessment and risk assessment.
AB  - A pronounced presence of toluene from rotogravure printed matter has been
      frequently observed indoors. However, its consequences to human health in the
      life cycle of magazines are poorly known. Therefore, we quantified human-health
      risks in indoor environments with Risk Assessment (RA) and impacts relative to
      the total impact of toxic releases occurring in the life cycle of a magazine with
      Life Cycle Assessment (LCA). We used a one-box indoor model to estimate toluene
      concentrations in printing facilities, newsstands, and residences in a best,
      average, and worst-case scenario. The modeled concentrations are in the range of
      the values measured in on-site campaigns. Toluene concentrations can be close or
      even surpass the occupational legal thresholds in printing facilities in
      realistic worst-case scenarios. The concentrations in homes can surpass the US
      EPA reference dose (69 MUg/kg/day) in worst-case scenarios, but are still at
      least 1 order of magnitude lower than in press rooms or newsstands. However,
      toluene inhaled at home becomes the dominant contribution to the total potential
      human toxicity impacts of toluene from printed matter when assessed with LCA,
      using the USEtox method complemented with indoor characterization factors for
      toluene. The significant contribution (44%) of toluene exposure in production,
      retail, and use in households, to the total life cycle impact of a magazine in
      the category of human toxicity, demonstrates that the indoor compartment requires
      particular attention in LCA. While RA works with threshold levels, LCA assumes
      that every toxic emission causes an incremental change to the total impact. Here,
      the combination of the two paradigms provides valuable information on the life
      cycle stages of printed matter. 

PMID- 24283299
TI  - microRNA profiling in patients with abdominal aortic aneurysms: the significance
      of miR-155.
AB  - AAA (abdominal aortic aneurysm) is a potentially life-threatening late-onset
      degenerative condition. miRNAs (microRNAs), the small non-coding RNA molecules
      that regulate gene expression, have been shown previously to be associated with a
      broad range of human pathologies, including cardiovascular diseases. The aim of
      the present study was to identify AAA-associated miRNAs potentially contributing
      to AAA pathology. We analysed the expression of 124 miRNAs within AAA biopsies
      and serum of ten patients undergoing AAA repair, and serum from ten age- and sex
      matched subjects without AAA, using the FlexmiRTM MicroRNA Assay. RNA extracted
      from the site of main AAA dilatation (AAA body) was compared with that extracted
      from the macroscopically non-dilated neck of the AAA (AAA neck). Similarly, RNA
      extracted from the serum of AAA patients (AAA serum) was compared with that
      extracted from age- and sex-matched controls (control serum). qPCR (quantitative
      real-time PCR), Western blot analysis and histology were performed using an
      independent set of six paired AAA body and neck biopsies to examine the validity
      of findings. Seven miRNAs were up-regulated [>2-fold difference, FDR (false
      discovery rate) <0.5] within AAA biopsies, of which miR-155 was the most
      differentially expressed (11.32-fold, FDR=0.414). This finding was confirmed by
      qPCR with the median relative expression of miR-155 being 3.26 and 0.63 within
      AAA body and AAA neck biopsies respectively (P=0.031). Circulating miR-155 was
      also increased in AAA patients compared with controls, with a 2.67-fold up
      regulation at borderline significance (FDR=0.554). Two immunologically important
      miR-155 target genes, CTLA4 (cytotoxic T-lymphocyte-associated protein) and
      SMAD2, were assessed and found to be significantly down-regulated within AAA
      bodies compared with AAA necks (P=0.032 and P=0.026) as determined by qPCR and
      Western blotting respectively. Histology demonstrated dense accumulation of T
      lymphocytes within the adventitial and outer medial layers of AAA body, but not
      neck tissue. The results of the present study suggest that miR-155 is
      overexpressed in AAA with potential implications in the pathogenesis of the
      condition. 

PMID- 24283300
TI  - Maternal blood pressure and dominant sleeping position may affect placental
      localization.
AB  - OBJECTIVE: This study investigates whether maternal socio-demographic and
      clinical characteristics influence the site of placental implantation so that
      placental localization and associated abnormalities can be predicted. METHODS:
      This study reviews 500 healthy women with singleton pregnancy that were
      consecutively admitted to the study center and eventually delivered healthy
      newborns. RESULTS: The most frequently observed sites of placentation were
      anterior uterine wall (53.2%), posterior uterine wall (28.8%), lateral uterine
      walls (10.0%) and uterine fundus (8.0%), respectively. The women with fundal
      placentation had significantly higher systolic and diastolic blood pressures (p =
      0.044 and p = 0.040, respectively). Supine sleeping position was more frequent in
      women with anterior placenta and (OR: 11.568, 95% CI: 2.720-49.193) and prone
      sleeping position was more frequent in women with posterior placenta (OR: 15.449,
      95% CI: 2.151-52.978) (p = 0.001). The women who favored to sleep in right
      lateral position were more likely to have lateral placentation, while the women
      who used to sleep in left lateral position were more likely to have fundal
      placentation (p = 0.001). CONCLUSIONS: Sleeping position in early pregnancy may
      influence placental implantation site. The probable mechanism may refer to the
      alterations in uterine perfusion which is induced by the change in systemic blood
      pressure and dominant sleeping position.

PMID- 24283301
TI  - Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a
      retrospective case series of 66 patients on chronic therapy.
AB  - OBJECTIVE. The relationship between metformin accumulation and lactate increase
      is still debated. This observational case series aims to evaluate the correlation
      of metformin plasma levels with the pH, lactate and creatinine levels, and with
      the mortality rate in selected patients with metformin accumulation confirmed
      through metformin plasma concentration detection at hospital admission. MATERIAL
      AND METHODS. All cases of lactic acidosis (pH, <= 7.35; arterial lactate, >= 5
      mmol/L) related to metformin accumulation (plasma level >= 4 mcg/mL) from 2007 to
      2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses
      were excluded. Epidemiological, medical history, clinical and laboratory data
      were evaluated in all cases. RESULTS. Sixty-six patients were included. Thirty
      one patients (47%) had contraindication to therapy with metformin. All patients
      showed severe lactic acidosis (pH, 6.91 +/- 0.18; lactate, 14.36 +/- 4.90 mmol/L)
      and acute renal failure (creatinine, 7.24 +/- 3.29 mg/dL). The mean metformin
      plasma concentration was 40.68 +/- 27.70 mcg/mL. Metformin plasma concentrations
      showed a correlation, statistically significant even if not strong, with
      creatinine (p = 0.002, R = 0.37), pH (p < 0.0001, R = - 0.43) and plasma lactate
      levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality
      (before discharge from ICU) was 26% (17 cases). Lactate and metformin
      concentrations had mean levels not statistically different in surviving and
      deceased patients. CONCLUSIONS. Patients on chronic therapy with metformin may
      develop a mitochondrial-related toxicity that should be considered when patients
      present with lactic acidosis, renal failure, and frequently, a medical history of
      gastrointestinal manifestations during the days preceding the hospital admission.
      The correlation between metformin plasma concentrations and creatinine, pH, and
      lactate levels seems to be related to the mechanism of action (inhibition of
      complex I of the mitochondrial respiratory chain) and to the kinetic properties
      (high distribution volume and low protein binding) of the drug. The relevant
      early mortality seems not correlated with the levels of metformin or lactates:
      this could be due to the possible role of concurrent illness even if, such as for
      the relationships with lactate and creatinine, a more proper toxicological
      evaluation could be obtained by assessing metformin erythrocyte concentrations
      instead of the plasmatic ones.

PMID- 24283302
TI  - New insights into root causes of pediatric accidental unsupervised ingestions of
      over-the-counter medications.
AB  - CONTEXT: Changes to regulations, packaging, and labeling and ongoing educational
      efforts are intended to support appropriate use of medicines. Yet annually poison
      centers receive > 500 000 reports of accidental or unsupervised exposure to
      medicines for children under 6 years of age. OBJECTIVE: To identify root (i.e.,
      fundamental and preventable) causes of accidental unsupervised ingestions (AUIs),
      we designed a questionnaire and conducted a follow-up survey of caregivers who
      contacted McNeil Consumer Healthcare (McNeil) following an AUI by a child under
      12 years of age. METHODS: Reports received between 1 October 2008 and 22 January
      2009 were screened retrospectively for specific Medical Dictionary of Regulatory
      Activities (MedDRA) Preferred Terms relating to AUIs. Using the questionnaire, we
      collected information about the child, caregiver, medicines involved in AUI,
      management of AUI, and storage location of medicines. RESULTS: Two hundred twenty
      reports met inclusion criteria and attempts to contact these caregivers were made
      throughout a 2-week period in March 2009; caregivers completed the questionnaire
      for 45 reports. All AUIs occurred in children under 7 years and 56% were boys. In
      56% of AUI cases, the child involved was the intended recipient of the medicine;
      in 71%, a pediatric medicine was involved. Most AUIs occurred in the child's
      home; most caregivers reported not observing the AUI. Sixty percent of caregivers
      reported that the medicine involved in AUI was not in the normal storage location
      when AUI occurred. Among children involved in AUIs, 84% did not experience any
      symptoms. Seven children experienced mild, self-limiting symptoms which resolved.
      AUIs often occurred < 24 h after last therapeutic use when the medicine was
      removed from its normal storage location. CONCLUSIONS: These new insights may
      help guide-targeted interventions and educational efforts to focus caregivers'
      attention to reengaging childproofing mechanisms and returning medicines to a
      secure location, high and out of sight, immediately after use.

PMID- 24283304
TI  - Spreading the warmth.

PMID- 24283313
TI  - Nurses to have new role in personal health budgets.

PMID- 24283303
TI  - GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma
      and Of its treatment with sorafeNib): second interim analysis.
AB  - BACKGROUND: GIDEON (Global Investigation of therapeutic DEcisions in
      hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) is a global,
      prospective, non-interventional study undertaken to evaluate the safety of
      sorafenib in patients with unresectable HCC in real-life practice, including
      Child-Pugh B patients who were excluded from clinical trials. METHODS: Patients
      with unresectable HCC, for whom the decision to treat with sorafenib, based on
      the approved label and prescribing guidelines, had been taken by their physician,
      were eligible for inclusion. Demographic data and disease/medical history were
      recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at
      follow-up visits. The second interim analysis was undertaken when ~1500 treated
      patients were followed up for >= 4 months. RESULTS: Of the 1571 patients
      evaluable for safety, 61% had Child-Pugh A status and 23% Child-Pugh B. The
      majority of patients (74%) received the approved 800 mg initial sorafenib dose,
      regardless of Child-Pugh status; however, median duration of therapy was shorter
      in Child-Pugh B patients. The majority of drug-related AEs were grade 1 or 2, and
      the most commonly reported were consistent with previous reports. The incidence
      and nature of drug-related AEs were broadly similar across Child-Pugh, Barcelona
      Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the
      overall population. CONCLUSIONS: Consistent with the first interim analysis,
      overall safety profile and dosing strategy are similar across Child-Pugh
      subgroups. Safety findings also appear comparable irrespective of initial
      sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.

PMID- 24283314
TI  - Burden on A&E must be eased to cope with seasonal demand.

PMID- 24283319
TI  - Political puzzle.

PMID- 24283323
TI  - Practice question.

PMID- 24283324
TI  - Disclosing a diagnosis of dementia: a background to the phenomenon.
AB  - The number of people with dementia who have not received a formal diagnosis is
      high, in the UK and also internationally. Government strategies aim to raise
      public and professional awareness about the condition and increase rates of
      timely diagnosis. Benefits associated with timely diagnosis include earlier
      access to medication and being able to plan future care. Despite these benefits,
      a number of factors contribute to delay in, or in some cases denial of, diagnosis
      to people with dementia. This article aims to provide nurses, who are important
      healthcare professionals in the diagnostic process, with an overview of the
      literature on disclosing diagnosis to people with dementia. 

PMID- 24283325
TI  - Barriers to keeping warm in later life.
AB  - AIM: To identify factors influencing older people's ability to keep warm and well
      in winter. METHOD: This qualitative study used in-depth individual interviews
      with older people (n=50) and health and social care staff,(n=25), alongside six
      focus groups with 43 participants and a consultation event. Temperatures were
      measured in the homes of the older people interviewed. Framework analysis
      techniques were used. FINDINGS: The data indicated a lack of awareness among
      participants of the importance to a person's health of keeping warm. A summary of
      findings related to the themes of awareness, money, mindset and machinery is
      presented here, with reflections on their relevance to nursing in terms of
      identifying older people at risk of the negative health effects of cold, their
      assessment and support. CONCLUSION: The study revealed a number of ways older
      people are vulnerable to cold at home. Timely interventions from nurses in
      various sectors could help avoid cold-related harm.

PMID- 24283326
TI  - An overview of chronic kidney disease in older people.
AB  - There is a lack of consensus about how early chronic kidney disease (CKD) should
      be diagnosed and managed in older people. Some believe that reduced renal
      function in older age is usually benign and that identifying it as a condition
      requiring medical intervention is inappropriate, whereas others believe it
      represents an important public health issue. This uncertainty is not reflected in
      management guidelines. There is no controversy, however, that advanced CKD is
      particularly dangerous in older people. They are at risk of acute kidney injury,
      often worsened by unenlightened medical management. As CKD advances towards end
      stage in older people, treatment choices are even more difficult to make and
      there is a need for insightful input from carers to optimise outcomes. 

PMID- 24283327
TI  - PTSD, comorbid depression, and the cortisol waking response in victims of
      intimate partner violence: preliminary evidence.
AB  - Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are two
      highly comorbid and debilitating disorders experienced by more than half of
      intimate partner violence victims (IPV). Hypothalamic-pituitary-adrenal (HPA)
      abnormalities are common in both disorders, though the direction of abnormalities
      often differs. The present study examined the relationship between comorbid PTSD
      and MDD, and the (salivary) cortisol waking response in 104 recently abused IPV
      victims. Waking cortisol levels, area under the waking curve with respect to
      ground (AUCg), and AUC with respect to increase (AUCi) were examined to determine
      the relation of HPA dynamics to comorbidity for basal versus more dynamic
      measures. Prior to accounting for comorbidity, women with PTSD or MDD showed
      significantly greater AUCi than women without the respective disorder. Accounting
      for comorbidity, PTSD only did not differ from other groups, while MDD only and
      PTSD + MDD showed greater AUCi than women with neither disorder. Results were
      nonsignificant for waking cortisol levels or AUCg. Results suggest that MDD
      drives elevated waking cortisol response, but not basal cortisol activity in
      recently abused IPV victims. Results demonstrate the importance of examining
      comorbid diagnoses and HPA activity from a dynamic perspective. Therapeutic
      implications are discussed. 

PMID- 24283329
TI  - Atomic force microscopic study of the structure of high-density polyethylene
      deformed in liquid medium by crazing mechanism.
AB  - A procedure has been developed for the direct atomic force microscopic (AFM)
      examination of the native structure of high-density polyethylene (HDPE) deformed
      in an adsorption-active liquid medium (AALM) by the crazing mechanism. The AFM
      investigation has been carried out in the presence of a liquid medium under
      conditions preventing deformed films from shrinkage. Deformation of HDPE in AALM
      has been shown to proceed through the delocalized crazing mechanism and result in
      the development of a fibrillar-porous structure. The structural parameters of the
      crazed polymer have been determined. The obtained AFM images demonstrate a
      nanosized nonuniformity of the deformation and enable one to observe the
      structural rearrangements that take place in the deformed polymer after removal
      of the liquid medium and stress relaxation. A structural similarity has been
      revealed between HDPE deformed in the AALM and hard elastic polymers. 

PMID- 24283328
TI  - Anaplasma phagocytophilum strains from voles and shrews exhibit specific ankA
      gene sequences.
AB  - BACKGROUND: Anaplasma phagocytophilum is a Gram-negative bacterium that
      replicates obligate intracellularly in neutrophils. It is transmitted by Ixodes
      spp. ticks and causes acute febrile disease in humans, dogs, horses, cats, and
      livestock. Because A. phagocytophilum is not transmitted transovarially in Ixodes
      spp., it is thought to depend on reservoir hosts to complete its life cycle. In
      Europe, A. phagocytophilum was detected in roe deer, red deer, wild boars, and
      small mammals. In contrast to roe deer, red deer and wild boars have been
      considered as reservoir hosts for granulocytic anaplasmosis in humans, dogs, and
      horses according to groESL- and ankA-based genotyping. A. phagocytophilum
      variants infecting small mammals in Europe have not been characterized
      extensively to date. RESULTS: We amplified the total ankA open reading frames of
      27 strains from voles and shrews. The analysis revealed that they harboured A.
      phagocytophilum strains that belonged to a distinct newly described ankA gene
      cluster. Further, we provide evidence that the heterogeneity of ankA gene
      sequences might have arisen via recombination. CONCLUSIONS: Based on ankA-based
      genotyping voles and shrews are unlikely reservoir hosts for granulocytic
      anaplasmosis in humans, dogs, horses, and livestock in Europe.

PMID- 24283330
TI  - Nutritional abrogation of photoimmunosuppression: in vivo investigations.
AB  - Skin cancer is a major public health concern, and the primary aetiological factor
      in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not
      only induces potentially mutagenic DNA damage but also suppresses cell-mediated
      immunity (CMI), allowing cancerous cells to escape destruction and progress to
      tumours. A considerable proportion of an individual's annual sun exposure is
      obtained outside the vacation period when topical and physical measures for
      photoprotection are irregularly used. Certain nutrients could provide an
      adjunctive protective role, and evidence is accruing from experimental studies to
      support their use in abrogation of photoimmunosuppression. Moreover, developments
      in clinical research methods to evaluate impact of solar-simulated radiation on
      cutaneous CMI allow the immune protective potential of nutritional agents to be
      examined in humans in vivo. This article summarises the mediation of CMI and its
      suppression by UVR, evaluates the methodology for quantitative assessment in
      vivo, reviews the human studies reported on nutritional abrogation of
      photoimmunosuppression including recent randomized controlled trials and
      discusses the mechanisms of photoprotection by the nutrients. This includes, in
      addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids
      and nicotinamide.

PMID- 24283331
TI  - Effects of transfer distance on spine kinematics for de-palletizing tasks.
AB  - One approach to reducing lateral bending and twisting in manual lifting tasks is
      to separate the lift's origin and destination, thereby encouraging lifters to
      step and turn their entire bodies. The objective of the current study was to
      determine how the degree to which one laterally bends and twists changes with
      transfer distance and initial lift height. Eighteen males lifted 10.9 kg boxes
      from a conveyor 0.5 m, 0.9 m, and 1.3 m above the floor and placed the boxes on a
      conveyor .50, .75, 1.00, 1.25, 1.50, or 1.75 m away at a height of .9 m. During
      picking, lateral bending and trunk extension velocities increased with increasing
      transfer distances. When placing the box, the degree of twisting decreased with
      increased transfer distance. In sum, when attempting to control the twisting and
      lateral bending during de-palletizing, the lift origin and destination should be
      separated by between 1 and 1.25 meters.

PMID- 24283332
TI  - Exposures to thoracic particulate matter, endotoxin, and glucan during post
      Hurricane Katrina restoration work, New Orleans 2005-2012.
AB  - In the aftermath of Hurricane Katrina, which devastated the city of New Orleans
      in August 2005, restoration workers were at risk for respiratory illness from
      exposure to airborne particles and microbial agents. In support of an
      epidemiologic investigation of this risk, an exposure assessment for restoration
      work activities (demolition, trash & debris management, landscape restoration,
      sewer/waterline repair, and mold remediation) was performed from 2005 to 2012.
      For 2005 and 2006, Occupational Safety and Health Administration (OSHA) data (n =
      730) for personal and area monitoring of total and respirable dust exposures of
      restoration workers were accessed and analyzed. The most significant exposures
      were for demolition work, with average respirable dust exposures in 2005 above
      the action level of 2.5 mg/m(3) and 17.6% of exposures exceeding the permissible
      exposure limit (PEL) (5 mg/m(3)). Additional personal and area monitoring for
      thoracic particulate matter was performed from 2007 to 2012 (n = 774) and samples
      were assayed for endotoxin and (1->3, 1->6)-beta-D-glucan (n = 202). In order to
      integrate the OSHA data with the later monitoring data, three independent
      predictive models were developed to convert total and respirable dust measures
      into the equivalent thoracic dust. The three models were not statistically
      different and the modeling results were in good agreement with an overall
      coefficient of variation of 16% for the thoracic dust means across work
      activities estimated by each of the three models. Overall, thoracic dust exposure
      levels decreased by about an order of magnitude within the first year after
      Katrina and then more gradually declined and stabilized through 2012. Estimated
      average exposures to endotoxin and microbial glucan in 2005 were as high as 256
      EU/m(3) and 118 MUg/m(3), respectively, and likewise were seen to decrease
      dramatically and stabilize after 2005. The results of this exposure assessment
      support previously published reports of respiratory illness including sinusitis,
      toxic pneumonitis, and Katrina Cough among restoration workers in the years
      immediately after the hurricane.

PMID- 24283333
TI  - Dermal absorption of chemicals: estimation by IH SkinPerm.
AB  - This article describes the IH SkinPerm mathematical tool for estimating dermal
      absorption. The first part provides the scientific background of the IH SkinPerm
      model, including the QSARs and the developed differential equations. Then the
      practical value of the tool is demonstrated through example dermal absorption
      assessments for substances with skin notations. IH SkinPerm simulates three types
      of dermal absorption scenarios relevant to occupational environments. The first
      is dermal absorption from instantaneous splash type exposures onto bare skin for
      pure liquids. The second estimates dermal absorption from the deposition of pure
      liquids over time. The third enables estimation of dermal uptake from an airborne
      vapor concentration. A simulation with IH SkinPerm was made using vapor
      absorption data published from volunteer exposure studies. Comparison of measured
      and estimated dermal absorbed dose showed IH SkinPerm estimated dermal absorbed
      dose was within a factor of 3 compared to the reported study values. IH SkinPerm
      accounts for substance volatility and evaporated mass and provides real-time
      description of dermal absorption with graphical displays and numerical outputs.
      To assess absorption resulting from dermal exposure scenarios, the mass of the
      substance loaded onto the skin, substance physical chemical properties, exposure
      duration, and the skin surface area affected are the only required input
      parameters. 

PMID- 24283334
TI  - Nitrous oxide as a tracer gas in the ASHRAE 110-1995 Standard.
AB  - ANSI/ASHRAE Standard 110 provides a quantitative method for testing the
      performance of laboratory fume hoods. Through release of a known quantity (4.0
      Lpm) of a tracer gas, and subsequent monitoring of the tracer gas concentration
      in the "breathing zone" of a mannequin positioned in front of the hood, this
      method allows for evaluation of laboratory hood performance. Standard 110
      specifies sulfur hexafluoride (SF6) as the tracer gas; however, suitable
      alternatives are allowed. Through three series of performance tests, this
      analysis serves to investigate the use of nitrous oxide (N2O) as an alternate
      tracer gas for hood performance testing. Single gas tests were performed
      according to ASHRAE Standard 110-1995 with each tracer gas individually. These
      tests showed identical results using an acceptance criterion of AU 0.1 with the
      sash half open, nominal 18 inches (0.46m) high, and the face velocity at a
      nominal 60 fpm (0.3 m/s). Most data collected in these single gas tests, for both
      tracer gases, were below the minimum detection limit, thus two dual gas tests
      were developed for simultaneous sampling of both tracer gases. Dual gas dual
      ejector tests were performed with both tracer gases released simultaneously
      through two ejectors, and the concentration measured with two detectors using a
      common sampling probe. Dual gas single ejector tests were performed with both
      tracer gases released though a single ejector, and the concentration measured in
      the same manner as the dual gas dual ejector tests. The dual gas dual ejector
      tests showed excellent correlation, with R typically greater than 0.9. Variance
      was observed in the resulting regression line for each hood, likely due to non
      symmetry between the two challenges caused by variables beyond the control of the
      investigators. Dual gas single ejector tests resulted in exceptional correlation,
      with R>0.99 typically for the consolidated data, with a slope of 1.0. These data
      indicate equivalent results for ASHRAE 110 performance testing using either SF6
      or N2O, indicating N2O as an applicable alternate tracer gas. 

PMID- 24283335
TI  - Mass balance source apportionment modeling of indoor air pollution exposures
      during the Ethiopian coffee ceremony.
AB  - Mass balance modeling was used to apportion previously measured carbon monoxide
      and respirable particle exposures of women preparing coffee during Ethiopian
      coffee ceremonies. The coffee ceremony generates smoke indoors from the use of
      charcoal and incense. This creates inhalation exposures, particularly for the
      women preparing the coffee. Understanding the health risks associated with this
      practice will be improved with knowledge of the relative contribution to
      combustion byproduct exposures from the different sources. Source fingerprints
      were developed in the laboratory for carbon monoxide and respirable particle
      emissions from charcoal and incense. A mass balance model determined that the
      majority of the carbon monoxide exposures were from charcoal use and that the
      respirable particle exposures were approximately half from incense and half from
      charcoal. Efforts to decrease health risks from these exposures must be directed
      by Ethiopian cultural stakeholders who understand the exposure conditions, the
      health risks, and the societal context. 

PMID- 24283336
TI  - Neither short-term sprint nor endurance training enhances thermal response to
      exercise in a hot environment.
AB  - Improvements in fitness from a brief period of physical training may elicit
      sufficient physiological adaptations to decrease thermal strain during exercise
      in the heat. This study tested heat adaptation from short-term endurance (ET) and
      sprint-interval (SIT) training in moderately fit individuals. The ET group (n =
      8) cycled at 65% [Formula: see text] for 8 sessions (4 sessions each at 60 and 90
      min, respectively) over two weeks, while the SIT group (n = 8) performed repeated
      30-s Wingate sprints (resistance 7.5% body mass; 4 sessions each of 4 and 5
      sprints, respectively). [Formula: see text] and heat stress testing (HST; 60 min
      cycling at 65% [Formula: see text] at 35oC, 40% relative humidity) were performed
      pre- and post-training. [Formula: see text]increased by 11% (p = 0.025) and 14%
      (p = 0.020) for the ET and SIT groups post-training, respectively. Thermal stress
      was similar pre- and post-training, with no significant difference in the rate of
      whole-body metabolic heat production (p = 0.106) for either group post-training.
      Cardiovascular improvement was evident with both ET and SIT, with a significant
      mean decrease (p = 0.014) in HR for both groups (ET: 146 +/- 15 beats.min(-1)pre
      vs. 142 +/- 12 beats.min(-1)post; SIT: 149 +/- 15 beats.min(-1)pre vs. 146 +/- 12
      beats.min(-1)post) during the HST post-training. However, mean sweat loss (p =
      0.248) and the rise in core temperature (p = 0. 260) did not change significantly
      comparing pre- and post-training HST. While short-term ET and SIT both induced
      significant improvements in aerobic fitness and decreased cardiovascular strain,
      neither elicited improved thermal responses during exercise in the heat and do
      not replace heat acclimatization.

PMID- 24283337
TI  - Influence of parameter values and variances and algorithm architecture in
      ConsExpo model on modeled exposures.
AB  - This study evaluated the influence of parameter values and variances and model
      architecture on modeled exposures, and identified important data gaps that
      influence lack-of-knowledge-related uncertainty, using Consexpo 4.1 as an
      illustrative case study. Understanding the influential determinants in exposure
      estimates enables more informed and appropriate use of this model and the
      resulting exposure estimates. In exploring the influence of parameter placement
      in an algorithm and of the values and variances chosen to characterize the
      parameters within ConsExpo, "sensitive" and "important" parameters were
      identified: product amount, weight fraction, exposure duration, exposure time,
      and ventilation rate were deemed "important," or "always sensitive." With this
      awareness, exposure assessors can strategically focus on acquiring the most
      robust estimates for these parameters. ConsExpo relies predominantly on three
      algorithms to assess the default scenarios: inhalation vapors evaporation
      equation using the Langmuir mass transfer, the dermal instant application with
      diffusion through the skin, and the oral ingestion by direct uptake algorithm.
      These algorithms, which do not necessarily render health conservative estimates,
      account for 87, 89 and 59% of the inhalation, dermal and oral default scenario
      assessments,respectively, according them greater influence relative to the less
      frequently used algorithms. Default data provided in ConsExpo may be useful to
      initiate assessments, but are insufficient for determining exposure acceptability
      or setting policy, as parameters defined by highly uncertain values produce
      biased estimates that may not be health conservative. Furthermore, this lack-of
      knowledge uncertainty makes the magnitude of this bias uncertain. Significant
      data gaps persist for product amount, exposure time, and exposure duration. These
      "important" parameters exert influence in requiring broad values and variances to
      account for their uncertainty. Prioritizing them for research will not only help
      fill a large and influential knowledge gap, but also lead to more accurate
      assessments and thus refine the studies informing policy decisions. 

PMID- 24283338
TI  - Case study: ultrafine particles exposure in apprentice welders.

PMID- 24283339
TI  - Case study: noise characterization and exposure at a ski resort.

PMID- 24283340
TI  - Analytical performance issues: quantifying response time in carbon monoxide
      monitors to produce high-resolution measurements.

PMID- 24283342
TI  - Bioinspired helical microswimmers based on vascular plants.
AB  - Plant-based bioinspired magnetically propelled helical microswimmers are
      described. The helical microstructures are derived from spiral water-conducting
      vessels of different plants, harnessing the intrinsic biological structures of
      nature. Geometric variables of the spiral vessels, such as the helix diameter and
      pitch, can be controlled by mechanical stretching for the precise fabrication and
      consistent performance of helical microswimmers. Xylem vessels of a wide variety
      of different plants have been evaluated for the consistency and reproducibility
      of their helical parameters. Sequential deposition of thin Ti and Ni layers
      directly on the spiral vessels, followed by dicing, leads to an extremely simple
      and cost-efficient mass-production of functional helical microswimmers. The
      resulting plant-based magnetic microswimmers display efficient propulsion, with a
      speed of over 250 MUm/s, as well as powerful locomotion in biological media such
      as human serum. The influence of actuation frequencies on the swimming velocity
      is investigated. Such use of plant vessels results in significant savings in the
      processing costs and provides an extremely simple, cost-effective fabrication
      route for the large-scale production of helical magnetic swimmers. 

PMID- 24283343
TI  - CO oxidation on TiO(2) (110) supported subnanometer gold clusters: size and shape
      effects.
AB  - We performed a comprehensive study of catalytic activities of subnanometer Au
      clusters supported on TiO2(110) surface (Aun/TiO2, n = 1-4, 7, 16-20) by means of
      density functional theory (DFT) calculations and microkinetics analysis. The
      creditability of the chosen DFT/microkienetics methodologies was demonstrated by
      the very good agreement between predicted catalytic activities with experimental
      measurement (J. Am. Chem. Soc, 2004, 126, 5682-5483) for the Au1-4/TiO2 and
      Au7/TiO2 benchmark systems. For the first time, the size- and shape-dependent
      catalytic activities of the subnanometer Au clusters (Au16-Au20) on TiO2 supports
      were systematically investigated. We found that catalytic activities of the
      Aun/TiO2 systems increase with the size n up to Au18, for which the hollow-cage
      Au18 isomer exhibits highest activity for the CO oxidation, with a reaction rate
      ~30 times higher than that of Au7/TiO2 system. In stark contrast, the pyramidal
      isomer of Au18 exhibits much lower activity comparable to the Au3-4/TiO2 systems.
      Moreover, we found that the hollow-cage Au18 is robust upon the soft-landing with
      an impact velocity of 200 m/s to the TiO2 substrate, and also exhibits thermal
      stability upon CO and O2 co-adsorption. The larger pyramidal Au19 and Au20
      clusters (on the TiO2 support) display much lower reaction rates than the
      pyramidal Au18. Results of rate of reactions for unsupported (gas-phase) and
      supported Au clusters can be correlated by a contour plot that illustrates the
      dependence of the reaction rates on the CO and O2 adsorption energies. With the
      TiO2 support, however, the catalytic activities can be greatly enhanced due to
      the weaker adsorption of CO on the TiO2 support than on the Au clusters, thereby
      not only the ratio of O2/CO adsorption energy and the probability for the O2 to
      occupy the Ti sites are increased but also the requirement for meeting the
      critical line becomes weaker. The obtained contour plot not only can provide
      guidance for the theoretical investigation of catalytic activity on other metal
      cluster/support systems, but also assist experimental design of optimal metal
      cluster/support systems to achieve higher catalytic efficiency. 

PMID- 24283344
TI  - Long-range sequencing revealed a new KIR3DL1*0150204 allele in 20 individuals of
      Asian descent.
AB  - The novel KIR3DL1*0150204 has four point mutations: 3037G>A, 4115A>G, 6053G>C,
      and 8034A>G compared to KIR3DL1*0150201. 

PMID- 24283346
TI  - Human acellular dermal wound matrix: evidence and experience.
AB  - A chronic wound fails to complete an orderly and timely reparative process and
      places patients at increased risk for wound complications that negatively impact
      quality of life and require greater health care expenditure. The role of
      extracellular matrix (ECM) is critical in normal and chronic wound repair. Not
      only is ECM the largest component of the dermal skin layer, but also ECM proteins
      provide structure and cell signalling that are necessary for successful tissue
      repair. Chronic wounds are characterised by their inflammatory and proteolytic
      environment, which degrades the ECM. Human acellular dermal matrices, which
      provide an ECM scaffold, therefore, are being used to treat chronic wounds. The
      ideal human acellular dermal wound matrix (HADWM) would support regenerative
      healing, providing a structure that could be repopulated by the body's cells.
      Experienced wound care investigators and clinicians discussed the function of
      ECM, the evidence related to a specific HADWM (Graftjacket((r)) regenerative
      tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San
      Antonio, TX), and their clinical experience with this scaffold. This article
      distills these discussions into an evidence-based and practical overview for
      treating chronic lower extremity wounds with this HADWM. 

PMID- 24283345
TI  - Recombinant production and characterization of full-length and truncated beta-1,3
      glucanase PglA from Paenibacillus sp. S09.
AB  - BACKGROUND: beta-1,3-Glucanases catalyze the hydrolysis of glucan polymers
      containing beta-1,3-linkages. These enzymes are of great biotechnological,
      agricultural and industrial interest. The applications of beta-1,3-glucanases is
      well established in fungal disease biocontrol, yeast extract production and wine
      extract clarification. Thus, the identification and characterization of novel
      beta-1,3-glucanases with high catalytic efficiency and stability is of particular
      interest. RESULTS: A beta-1,3-glucanase gene designated PglA was cloned from a
      newly isolated strain Paenibacillus sp. S09. The gene PglA contained a 2631-bp
      open reading frame encoding a polypeptide of 876 amino acids which shows 76%
      identity with the beta-1,3-glucanase (BglH) from Bacillus circulans IAM1165. The
      encoded protein PglA is composed of a signal peptide, an N-terminal leader
      region, a glycoside hydrolase family 16 (GH16) catalytic domain and a C-terminal
      immunoglobulin like (Ig-like) domain. The Escherichia coli expression system of
      PglA and five truncated derivatives containing one or two modules was constructed
      to investigate the role of catalytic and non-catalytic modules. The pH for
      optimal activity of the enzymes was slightly affected (pH 5.5-6.5) by the
      presence of different modules. However, the temperature for optimal activity was
      strongly influenced by the C-terminal domain and ranged from 50 to 60 degrees C.
      Deletion of C-terminal domain resulted in obviously enhancing enzymatic
      thermostability. Specific activity assay indicated that PglA specifically
      hydrolyzes beta-1,3-glucan. Insoluble beta-1,3-glucan binding and hydrolysis were
      boosted by the presence of N-and C-terminal domains. Kinetic analysis showed that
      the presence of N-and C-terminus enhances the substrate affinity and catalytic
      efficiency of the catalytic domain toward laminarin. Carbohydrate-binding assay
      directly confirmed the binding capabilities of the N-and C-terminal domains.
      CONCLUSIONS: This study provides new insight into the impacts of non-catalytic
      modules on enzymatic properties of beta-1,3-glucanase. Activity comparison of
      full-length PglA and truncated forms revealed the negative effect of C-terminal
      region on thermal stability of the enzyme. Both the N-and C-terminal domains
      exerted strong binding activity toward insoluble beta-1,3-glucan, and could be
      classified into CBM families.

PMID- 24283347
TI  - Fe L-edge X-ray absorption spectra of Fe(II) polypyridyl spin crossover complexes
      from time-dependent density functional theory.
AB  - L-edge near-edge X-ray fine structure spectroscopy (NEXAFS) has become a powerful
      tool to study the electronic structure and dynamics of metallo-organic and
      biological compounds in solution. Here, we present a series of density functional
      theory calculations of Fe L-edge NEXAFS for spin crossover (SCO) complexes within
      the time-dependent framework. Several key factors that control the L-edge
      excitations have been carefully examined using an Fe(II) polypyridyl complex
      [Fe(tren(py)3)](2+) (where tren(py)3 = tris(2-pyridylmethyliminoethyl)amine) as a
      model system. It is found that the electronic spectra of the low-spin (LS,
      singlet), intermediate-spin (IS, triplet), and high-spin (HS, quintet) states
      have distinct profiles. The relative energy positions, but not the spectral
      profiles, of different spin states are sensitive to the choice of the
      functionals. The inclusion of the vibronic coupling leads to almost no visible
      change in the resulting NEXAFS spectra because it is governed only by low
      frequency modes of less than 500 cm(-1). With the help of the molecular dynamics
      sampling in acetonitrile at 300 K, our calculations reveal that the thermal
      motion can lead to a noticeable broadening of the spectra. The main peak position
      is strongly associated with the length of the Fe-N bond. 

PMID- 24283348
TI  - Heidegger, lived experience and method.
AB  - AIM: A discussion of the assumption that Heidegger's philosophy in Being And Time
      provides a warrant for the study of lived experience. BACKGROUND: It is generally
      assumed, in nursing as in other disciplines, that Heidegger's philosophy points,
      uncontroversially, to the study of lived experience. It is also assumed that
      studies of this type will take the form of qualitative interviews which seek to
      explore the respondent's experience of a particular phenomenon and to elicit the
      meanings which the individual concerned attaches to that experience. DATA
      SOURCES: Being And Time; the philosophical literature on Heidegger since 1999;
      the literature of experimental social psychology, 1970-2012. CONCLUSIONS:
      According to Heidegger, there is no such thing as 'lived experience'. The concept
      is embedded in the subject-object dualism that he is attempting to dismantle. In
      Heideggerian terms, interviews intended to explore 'lived experience' can only
      reproduce the voice of das Man, the 'They', not the voice of unique individuals.
      Methods more in keeping with Heidegger's philosophy include observation,
      naturalistic experiments, some forms of discourse analysis and conceptually
      associated lines of enquiry involving vocabularies of motive, scripts and the
      performative aspects of language use. IMPLICATIONS FOR NURSING: Nursing
      researchers who wish to embrace Heidegger's philosophy as a basis for their work
      should abandon 'lived experience' interviews and adopt one of the alternative
      methods suggested above. Nursing researchers who wish to continue with 'lived
      experience' interviews should seek an alternative philosophical or theoretical
      basis for their work.

PMID- 24283349
TI  - SN algorithm: analysis of temporal clinical data for mining periodic patterns and
      impending augury.
AB  - BACKGROUND: EHR (Electronic Health Record) system has led to development of
      specialized form of clinical databases which enable storage of information in
      temporal prospective. It has been a big challenge for mining this form of
      clinical data considering varied temporal points. This study proposes a conjoined
      solution to analyze the clinical parameters akin to a disease. We have used
      "association rule mining algorithm" to discover association rules among clinical
      parameters that can be augmented with the disease. Furthermore, we have proposed
      a new algorithm, SN algorithm, to map clinical parameters along with a disease
      state at various temporal points. RESULT: SN algorithm is based on Jacobian
      approach, which augurs the state of a disease 'Sn' at a given temporal point 'Tn'
      by mapping the derivatives with the temporal point 'T0', whose state of disease
      'S0' is known. The predictive ability of the proposed algorithm is evaluated in a
      temporal clinical data set of brain tumor patients. We have obtained a very high
      prediction accuracy of ~97% for a brain tumor state 'Sn' for any temporal point
      'Tn'. CONCLUSION: The results indicate that the methodology followed may be of
      good value to the diagnostic procedure, especially for analyzing temporal form of
      clinical data.

PMID- 24283350
TI  - Community-based distribution of misoprostol to prevent postpartum haemorrhage at
      home births: results from operations research in rural Ghana.
AB  - OBJECTIVE: To report on a rigorous distribution and monitoring plan to track
      misoprostol for community-based distribution to reduce postpartum haemorrhage
      (PPH) in rural Ghana. DESIGN: Operations research. SETTING: Rural Ghana. SAMPLE:
      Women in third trimester of pregnancy presenting to primary health centres (PHCs)
      for antenatal care (ANC). METHODS: Ghana Health Service (GHS), Millennium Village
      Projects, and the University of Illinois at Chicago conducted an operations
      research study designed to assess the safety, feasibility, and acceptability of
      community-based distribution of misoprostol to prevent PPH at home deliveries in
      rural Ghana. One thousand doses (3000 tablets, 200 MUg each) were obtained from
      the Family Health Division of GHS. Three 200-MUg tablets of misoprostol (600 MUg)
      in foil packets were packaged together in secured transparent plastic packets
      labelled with pictorial messages and distributed to midwives at seven PHCs for
      distribution to pregnant women. MAIN OUTCOME MEASURES: Correct use of misoprostol
      in home deliveries and retrieval of unused misoprostol doses, PPH rates and
      maternal mortality. RESULTS: Of the 999 doses distributed to midwives, 982
      (98.3%) were successfully tracked, with a 1.7% lost to follow-up rate. Midwives
      distributed 654 doses to women at third-trimester ANC visits. Of women who had
      misoprostol to use at home, 81% had an institutional delivery and were able to
      return the misoprostol safely to the midwife. Of the women that used misoprostol,
      99% used the misoprostol correctly. CONCLUSIONS: This study clearly demonstrates
      that misoprostol distributed antenatally to pregnant women can be used accurately
      and reliably by rural Ghanaian women, and should be considered for policy
      implementation across Ghana and other countries with high home birth rates and
      maternal mortality ratios.

PMID- 24283353
TI  - Reflections and expectations.

PMID- 24283355
TI  - The history of NFOG and Acta Obstetricia et Gynecologica Scandinavica 1921-2011.

PMID- 24283352
TI  - Flagellar central pair assembly in Chlamydomonas reinhardtii.
AB  - BACKGROUND: Most motile cilia and flagella have nine outer doublet and two
      central pair (CP) microtubules. Outer doublet microtubules are continuous with
      the triplet microtubules of the basal body, are templated by the basal body
      microtubules, and grow by addition of new subunits to their distal ("plus") ends.
      In contrast, CP microtubules are not continuous with basal body microtubules,
      raising the question of how these microtubules are assembled and how their
      polarity is established. METHODS: CP assembly in Chlamydomonas reinhardtii was
      analyzed by electron microscopy and wide-field and super-resolution
      immunofluorescence microscopy. To analyze CP assembly independently from
      flagellar assembly, the CP-deficient katanin mutants pf15 or pf19 were mated to
      wild-type cells. HA-tagged tubulin and the CP-specific protein hydin were used as
      markers to analyze de novo CP assembly inside the formerly mutant flagella.
      RESULTS: In regenerating flagella, the CP and its projections assemble near the
      transition zone soon after the onset of outer doublet elongation. During de novo
      CP assembly in full-length flagella, the nascent CP was first apparent in a
      subdistal region of the flagellum. The developing CP replaces a fibrous core that
      fills the axonemal lumen of CP-deficient flagella. The fibrous core contains
      proteins normally associated with the C1 CP microtubule and proteins involved in
      intraflagellar transport (IFT). In flagella of the radial spoke-deficient mutant
      pf14, two pairs of CPs are frequently present with identical correct polarities.
      CONCLUSIONS: The temporal separation of flagellar and CP assembly in dikaryons
      formed by mating CP-deficient gametes to wild-type gametes revealed that the
      formation of the CP does not require proximity to the basal body or transition
      zone, or to the flagellar tip. The observations on pf14 provide further support
      that the CP self-assembles without a template and eliminate the possibility that
      CP polarity is established by interaction with axonemal radial spokes. Polarity
      of the developing CP may be determined by the proximal-to-distal gradient of
      precursor molecules. IFT proteins accumulate in flagella of CP mutants; the
      abnormal distribution of IFT proteins may explain why these flagella are often
      shorter than normal.

PMID- 24283356
TI  - Ovarian granulosa cell tumor and increased risk of breast cancer.
AB  - Granulosa cell tumor of the ovary (GCT) is a rare neoplasm. The tumor often
      secretes estrogens and then presents at an earlier stage due to hormone-related
      symptoms. GCT women are at increased risk of endometrial carcinoma, but there is
      only limited information about GCTs and potential association to other hormone
      related neoplasms such as breast cancer. We conducted a retrospective follow-up
      study on 163 women with GCT. Medical records and histological sections were
      reviewed and a search in the pathology registry performed. Eight [95% confidence
      interval (CI); 3.4-15.8] GCT women were diagnosed with a breast neoplasm; one
      with Paget's disease of the nipple and seven with breast carcinoma. Based on
      calculations using incidence rates on breast cancer among Danish women, we would
      have expected 2.5 cases of breast cancer. The odds ratio was 3.3 (95% CI, 1.6
      6.6), suggesting an increased risk of breast cancer in GCT women.

PMID- 24283351
TI  - Comparison of the antibacterial activity of essential oils and extracts of
      medicinal and culinary herbs to investigate potential new treatments for
      irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional
      gastrointestinal disorder, which may result from alteration of the
      gastrointestinal microbiota following gastrointestinal infection, or with
      intestinal dysbiosis or small intestinal bacterial overgrowth. This may be
      treated with antibiotics, but there is concern that widespread antibiotic use
      might lead to antibiotic resistance. Some herbal medicines have been shown to be
      beneficial, but their mechanism(s) of action remain incompletely understood. To
      try to understand whether antibacterial properties might be involved in the
      efficacy of these herbal medicines, and to investigate potential new treatments
      for IBS, we have conducted a preliminary study in vitro to compare the
      antibacterial activity of the essential oils of culinary and medicinal herbs
      against the bacterium, Esherichia coli. METHODS: Essential oils were tested for
      their ability to inhibit E. coli growth in disc diffusion assays and in liquid
      culture, and to kill E. coli in a zone of clearance assay. Extracts of coriander,
      lemon balm and spearmint leaves were tested for their antibacterial activity in
      the disc diffusion assay. Disc diffusion and zone of clearance assays were
      analysed by two-tailed t tests whereas ANOVA was performed for the turbidometric
      assays. RESULTS: Most of the oils exhibited antibacterial activity in all three
      assays, however peppermint, lemon balm and coriander seed oils were most potent,
      with peppermint and coriander seed oils being more potent than the antibiotic
      rifaximin in the disc diffusion assay. The compounds present in these oils were
      identified by gas chromatography mass spectrometry. Finally, extracts were made
      of spearmint, lemon balm and coriander leaves with various solvents and these
      were tested for their antibacterial activity against E. coli in the disc
      diffusion assay. In each case, extracts made with ethanol and methanol exhibited
      potent antibacterial activity. CONCLUSIONS: Many of the essential oils had
      antibacterial activity in the three assays, suggesting that they would be good
      candidates for testing in clinical trials. The observed antibacterial activity of
      ethanolic extracts of coriander, lemon balm and spearmint leaves suggests a
      mechanistic explanation for the efficacy of a mixture of coriander, lemon balm
      and mint extracts against IBS in a published clinical trial.

PMID- 24283357
TI  - Scarring of lupus miliaris disseminatus faciei: treatment with a combination of
      trichloroacetic acid and carbon dioxide laser.
AB  - We present a case of a 35-year-old man having a 12-month history of multiple
      reddish-brown papules on the chin, forehead, cheeks, and eyelids. Histopathologic
      findings revealed epithelioid cell granulomas with central necrosis consistent
      with a diagnosis of lupus miliaris disseminatus faciei. After 9 months of
      combined treatment with ethambutol, rifampin, and pyrazinamide, most lesions
      gradually resolved but remained as severe disfiguring scars. After 10 sessions of
      treatments with 100% trichloroacetic acid and CO2 laser, the lupus miliaris
      disseminatus faciei scars have been much improved and the patient has never
      experienced a recurrence of disease during subsequent years of follow-up. 

PMID- 24283358
TI  - Efficacy of localized phototherapy and photodynamic therapy for psoriasis: a
      systematic review and meta-analysis.
AB  - Localized phototherapy including topical psoralen plus ultraviolet A (PUVA) and
      targeted ultraviolet B (UVB), and photodynamic therapy (PDT) have been
      increasingly used in the treatment of localized psoriasis. Yet, there are no
      systematic reviews or meta-analyses that scientifically evaluated the pooled
      efficacy of these treatments in psoriasis. We searched Medline, Embase, and
      Cochrane databases during the period of January 1980 to June 2012. Our systematic
      search resulted in 765 studies, 23 of them were included in the review. The
      primary outcome was 75% reduction in severity score from baseline. A meta
      analysis using random effect model found topical PUVA to be more effective than
      non-laser targeted UVB [odds ratio: 3.48 (95% confidence interval 0.56-21.84), P
      = 0.183]. The pooled effect estimate of the efficacy (75% reduction in severity
      score) of topical PUVA, targeted UVB, and PDT were as follows: 77% (topical
      PUVA), 61% (targeted UVB), and 22% (PDT). Topical PUVA and targeted UVB
      phototherapy are very effective in the treatment of localized psoriasis. Topical
      PUVA seems more effective than non-laser targeted UVB phototherapy. On the other
      hand, PDT has low efficacy and high percentage of side effects in treating
      localized psoriasis. 

PMID- 24283359
TI  - A model to estimate the population contributing to the wastewater using samples
      collected on census day.
AB  - An important uncertainty when estimating per capita consumption of, for example,
      illicit drugs by means of wastewater analysis (sometimes referred to as "sewage
      epidemiology") relates to the size and variability of the de facto population in
      the catchment of interest. In the absence of a day-specific direct population
      count any indirect surrogate model to estimate population size lacks a standard
      to assess associated uncertainties. Therefore, the objective of this study was to
      collect wastewater samples at a unique opportunity, that is, on a census day, as
      a basis for a model to estimate the number of people contributing to a given
      wastewater sample. Mass loads for a wide range of pharmaceuticals and personal
      care products were quantified in influents of ten sewage treatment plants (STP)
      serving populations ranging from approximately 3500 to 500 000 people. Separate
      linear models for population size were estimated with the mass loads of the
      different chemical as the explanatory variable: 14 chemicals showed good, linear
      relationships, with highest correlations for acesulfame and gabapentin. De facto
      population was then estimated through Bayesian inference, by updating the
      population size provided by STP staff (prior knowledge) with measured chemical
      mass loads. Cross validation showed that large populations can be estimated
      fairly accurately with a few chemical mass loads quantified from 24-h composite
      samples. In contrast, the prior knowledge for small population sizes cannot be
      improved substantially despite the information of multiple chemical mass loads.
      In the future, observations other than chemical mass loads may improve this
      deficit, since Bayesian inference allows including any kind of information
      relating to population size. 

PMID- 24283361
TI  - Association between seven common OPG genetic polymorphisms and osteoporosis risk:
      a meta-analysis.
AB  - Functional polymorphisms of the osteoprotegerin (OPG) gene are known to be
      involved in bone mineral density and the development of osteoporosis; however,
      some conflicting results have been reported. The aim of this meta-analysis is to
      provide a relatively comprehensive assessment of the relationship between seven
      common OPG genetic polymorphisms (T149C, A163G, G209A, T245G, T950C, G1181C, and
      C1217T) and osteoporosis risk. A literature search for eligible studies published
      before August 1st, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane
      Library, and CNKI (China National Knowledge Infrastructure) databases. Pooled
      odds ratios and their corresponding 95% confidence intervals were used to
      evaluate the strength of the association under fixed- or random-effect models
      according to a heterogeneity test. All analyses were performed using the STATA
      software, version 12.0. Fourteen case-control studies with a total of 2383
      osteoporosis cases and 2280 healthy controls were included in this meta-analysis.
      Among the seven polymorphisms, A163G and G1181C revealed significant associations
      with osteoporosis risk. For A163G (rs3102735), the combined results showed that
      the G allele of the A163G polymorphism may be associated with an increased risk
      of osteoporosis. Stratified analyses showed that the magnitude of the effect was
      similar in Caucasian and postmenopausal woman subgroups. For G1181C (rs2073618),
      however, we found that individuals with the C allele of the G1181C polymorphism
      had a decreased risk of osteoporosis, especially in Asian and postmenopausal
      woman subgroups. In summary, this meta-analysis indicated that the G allele of
      the OPG A163G polymorphism might increase osteoporosis risk in Caucasians,
      whereas individuals with the C allele of the G1181C polymorphism had a decreased
      risk of osteoporosis, especially in Asians. Both of these effects were observed
      in postmenopausal women. These polymorphisms could probably be used with other
      genetic markers together to identify individuals at a high risk of osteoporosis. 

PMID- 24283360
TI  - MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of
      scirrhous type gastric cancer.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. In
      particular, scirrhous type GC is highly metastatic and is characterized
      clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs)
      play crucial roles in cancer development and progression. In the present study,
      we identified several miRNAs that are expressed at higher levels in scirrhous
      type GC than in non-scirrhous type GC by miRNA microarray analysis. Among these,
      microRNA-143 (miR-143) expression was higher in scirrhous type GC than in non
      scirrhous types of GC. In situ hybridization and quantitative RT-PCR analysis
      showed that miR-143 is expressed by stromal fibroblasts but not by cancer cells.
      In stromal cells, miR-143 enhanced collagen type III expression in normal gastric
      fibroblasts and cancer-associated fibroblasts through activation of transforming
      growth factor-beta)/SMAD signaling. Furthermore, high miR-143 expression in GC
      was associated with worse cancer-specific mortality (P = 0.0141). Multivariate
      analysis revealed that miR-143 was an independent prognostic factor. Treatment of
      GC cell lines with 5-aza-2'-deoxycytidine restored the expression of miR-143, and
      precursor miR-143 caused the inhibition of cancer cell invasion. These data
      suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of
      collagen expression in stromal fibroblasts and that miR-143 expression serves as
      a prognostic marker of GC. 

PMID- 24283362
TI  - High glucose modulates antiproliferative effect and cytotoxicity of 5
      fluorouracil in human colon cancer cells.
AB  - 5-Fluorouracil (5-FU)-based chemotherapy is widely used for the treatment of
      colorectal cancer (CRC). While optimal doses of 5-FU are generally established
      based on a patient's estimated body surface area, the plasma concentrations of 5
      FU vary among patients. In addition, hyperglycemia in patients with CRC has been
      reported as a risk factor in poor prognosis. The aim of the present study was to
      investigate whether hyperglycemia affects antiproliferative effect of 5-FU on the
      human colon cancer cells (SW480, SW620, LoVo, and HCT116). Growth inhibition of 5
      FU was accessed by WST-8 assay. The effect of high glucose (HG, 15 mM) and 5-FU
      on the cellular proliferation was evaluated by flow cytometry analysis using 5
      ethynyl-2'-deoxy-uridine (EdU) incorporation plus 7-AAD. Cell death was
      determined by flow cytometry using Annexin V-FITC and PI. The results showed that
      HG, compared to physiological normal glucose (NG) concentration (5 mM), leads to
      increased cell proliferation and increased GI50 of 5-FU in the four colon cancer
      cell lines. When the cells were pretreated with a low-dose 5-FU in NG condition,
      subsequent HG treatment eliminated inhibitory effect of 5-FU in cancer cell
      growth. In the presence of 5-FU (0.5 MUg/mL for LoVo and HCT116; 1 MUg/mL for
      SW480 and SW620), culture with HG for 72 h does not significantly altered cell
      cycle profile in the four cell lines but significantly increased DNA replication
      in SW620 (21%) and LoVo (17%). Flow cytometric analysis showed that HG protects
      cells against 5-FU-induced cell death in SW480. Finally, HG did not alter
      intracellular level of reactive oxygen species (ROS), although 5-FU indeed
      induced higher intracellular level of ROS. In conclusion, HG attenuates growth
      inhibition of 5-FU and our results indicate that decreased cell death and
      increased DNA replication may account for the attenuating effect of a HG
      environment on 5-FU-induced tumor growth inhibition.

PMID- 24283363
TI  - Role of the PI3K/AKT pathway in modulating cytoskeleton rearrangements and
      phenotype switching in rat pulmonary arterial vascular smooth muscle cells.
AB  - Pulmonary arterial smooth muscle cell (PASMC) phenotype switching, which is
      characterized by changes in smooth muscle (SM)-specific gene expression,
      contributes to vascular remodeling in pulmonary hypertension. In addition, it has
      been shown that the transcription of SM-specific genes is modulated by
      cytoskeleton rearrangement. However, the intracellular mechanisms and signaling
      pathways that regulate these relationships are largely unknown. In the present
      study, we aimed to investigate the roles that phosphoinositide 3-kinase (PI3K)
      and protein kinase B (PKB), also known as AKT, play in modulating the
      cytoskeleton and phenotype of rat PASMCs. To observe the downstream effects of
      inhibiting or enhancing PI3K/AKT pathway activity, we used various approaches to
      manipulate protein function and gene expression. Treatment of PASMCs with
      platelet-derived growth factor (PDGF)-BB or PIK3CA-adenovirus induced
      cytoskeleton rearrangements and downregulated SM22alpha and alpha-SM actin gene
      expression. Inhibition of PI3K led to blocking of AKT phosphorylation and
      attenuated the PDGF-BB-induced downregulation of F-actin and SM-specific genes,
      the downstream effector of PI3K. The decrease in SM22alpha and alpha-SM actin
      mRNA levels induced by PDGF-BB was markedly and reproducibly blocked by LY294002.
      PI3K/AKT pathway plays a vital role in the modulation of PASMCs cytoskeleton
      rearrangement and phenotype switching. 

PMID- 24283365
TI  - Organizational readiness for knowledge translation in chronic care: a review of
      theoretical components.
AB  - BACKGROUND: With the persistent gaps between research and practice in healthcare
      systems, knowledge translation (KT) has gained significance and importance. Also,
      in most industrialized countries, there is an increasing emphasis on managing
      chronic health conditions with the best available evidence. Yet, organizations
      aiming to improve chronic care (CC) require an adequate level of organizational
      readiness (OR) for KT. OBJECTIVES: The purpose of this study is to review and
      synthesize the existing evidence on conceptual models/frameworks of
      Organizational Readiness for Change (ORC) in healthcare as the basis for the
      development of a comprehensive framework of OR for KT in the context of CC. DATA
      SOURCES: We conducted a systematic review of the literature on OR for KT in CC
      using Pubmed, Embase, CINAHL, PsychINFO, Web of Sciences (SCI and SSCI), and
      others. Search terms included readiness; commitment and change; preparedness;
      willing to change; organization and administration; and health and social
      services. STUDY SELECTION: The search was limited to studies that had been
      published between the starting date of each bibliographic database (e.g., 1964
      for PubMed) and November 1, 2012. Only papers that refer to a theory, a
      theoretical component from any framework or model on OR that were applicable to
      the healthcare domain were considered. We analyzed data using conceptual mapping.
      DATA EXTRACTION: Pairs of authors independently screened the published literature
      by reviewing their titles and abstracts. Then, the two same reviewers appraised
      the full text of each study independently. RESULTS: Overall, we found and
      synthesized 10 theories, theoretical models and conceptual frameworks relevant to
      ORC in healthcare described in 38 publications. We identified five core concepts,
      namely organizational dynamics, change process, innovation readiness,
      institutional readiness, and personal readiness. We extracted 17 dimensions and
      59 sub-dimensions related to these 5 concepts. CONCLUSION: Our findings provide a
      useful overview for researchers interested in ORC and aims to create a consensus
      on the core theoretical components of ORC in general and of OR for KT in CC in
      particular. However, more work is needed to define and validate the core elements
      of a framework that could help to assess OR for KT in CC.

PMID- 24283364
TI  - The occurrence of fetal microchimeric cells in endometrial tissues is a very
      common phenomenon in benign uterine disorders, and the lower prevalence of fetal
      microchimerism is associated with better uterine cancer prognoses.
AB  - This is the first study carried out to describe the role of fetal microchimerism
      (FM) in the pathogenesis of uterine cancer. The prevalence and concentration of
      male fetal microchimeric cells (FMCs) were examined in endometrial tissues in
      relation to subtypes of uterine cancer, and the histological grade and stage of
      the tumor. FM occurrence was analyzed in relation to risk factors, including
      hypertension, obesity, type 2 diabetes, dyslipidemia, age at cancer diagnosis,
      and patient pregnancy history. The prevalence and concentration of FMCs were
      examined in endometrial tissues using real-time polymerase chain reaction, SRY
      and beta-globin sequences as markers for male fetal FMCs and total DNA. The
      studied group involved 47 type 1 endometrial cancers, 28 type 2 endometrial
      cancers, and 41 benign uterine diseases. While the prevalence of FM was decreased
      only in type 1 endometrial cancer, compared with benign uterine disorders (38.3%
      vs.70.7%; odds ratio [OR]=0.257, 95% confidence interval [CI]: 0.105 to 0.628,
      p=0.003), FMC concentrations did not differ within examined groups. The lower FM
      prevalence was detected in low-grade (grade 1 and grade 2) endometrioid cancer
      (38.3% vs. 70.7%, OR=0.256, 95% CI: 0.105 to 0.627, p=0.003) and in FIGO 1 tumors
      (40.7% vs. 70.7%, OR=0.285, 95% CI: 0.120 to 0.675, p=0.004). No correlation
      between FM prevalence or FMC concentrations and risk factors was demonstrated. A
      lower prevalence of male FM seemed to be associated with better prognoses in
      uterine cancer based on tumor subtype, histological grade, and stage of the
      tumor. 

PMID- 24283366
TI  - Clinical trial of expectant management of severe preeclampsia that develops at
      <32 weeks' gestation at a Japanese perinatal center.
AB  - OBJECTIVE: This study was to examine the clinical usefulness of expectant
      management of early-onset severe preeclampsia. METHODS: We reviewed the obstetric
      records of all Japanese singleton deliveries at >=22 weeks' gestation managed at
      Japanese Red Cross Katsushika Maternity Hospital between 2007 and 2012. We
      compared the obstetric characteristics and perinatal outcomes between the cases
      of deliveries before (n = 19) and after completion of corticosteroids (n = 30)
      (immediate delivery versus expectant management). RESULTS: Although the
      gestational age at delivery in the patients expectantly managed was higher than
      that in the patients required immediate deliveries (31.0 versus 29.3 weeks), the
      difference in the incidence of neonatal respiratory distress syndrome between the
      two groups did not reach the statistical significance (74 versus 47%, p = 0.06).
      The incidence of pulmonary edema in the patients expectantly managed was
      significantly higher than that in the patients required immediate deliveries
      within the first 48 h (20 versus 0%, p = 0.04). CONCLUSION: The current results
      could not support the clinical usefulness of expectant management of early-onset
      severe preeclampsia.

PMID- 24283367
TI  - Antifreeze protein activity in Arctic cryoconite bacteria.
AB  - Fourteen Arctic bacterial strains belonging to five genera, Cryobacterium,
      Leifsonia, Polaromonas, Pseudomonas, and Subtercola isolated from sediments found
      in cryoconite holes of Arctic glaciers, were subjected to screening for
      antifreeze proteins (AFPs). Eight strains showed AFP activity, and six strains of
      four species were further characterized. Pseudomonas ficuserectae exhibited a
      high thermal hysteresis (TH) activity. Ice recrystallization inhibition (IRI)
      activity was observed in most cultures at low protein concentration. Bacterial
      AFPs produced rounded shape of ice crystals that did not change their size and
      morphology within the TH window. Cry-g (P. ficuserectae) failed to inhibit ice
      recrystallization, indicating that the IRI activity of the AFPs does not relate
      to the strength of TH activity. SDS-PAGE analysis of the AFPs suggests their
      apparent molecular weights to be around 23 kDa. This study is significant as it
      screens several species of Arctic bacterial strains for AFP activity. So far,
      only one species of bacteria, Pseudomonas putida, was reported from the Arctic to
      produce AFPs. N-terminal amino acid sequence analysis shows that the bacterial
      AFPs isolated belong to the AFP family IBP-1, which is known to have an important
      physiological role in the cold environment. AFPs of glacier cryoconite habitat
      have been discussed.

PMID- 24283368
TI  - Polarization switchable diffraction based on subwavelength plasmonic
      nanoantennas.
AB  - We prove theoretically and experimentally the concept of polarization holography
      by producing visible diffraction through radiation emitted by plasmonic
      nanoantennas. We show a methodology to selectively activate the nanoantenna
      emission by controlling the orientation of the electric field of a beam.
      Additionally, we demonstrate that it is possible to superpose two independent
      transverse nanoantennas in the same plane without producing interference in their
      radiated field. Hence, we introduce an alternative view to the traditional
      concept of holography where fringes (or diffractive units) are band-limited to
      half the wavelength. 

PMID- 24283369
TI  - Trace metal levels in water, fish, and sediment from River Nile, Egypt: potential
      health risks assessment.
AB  - The purposes of this study were to describe the impact of metal pollution on the
      main economic fish species Tilapia nilotica and to assess the potential health
      risk from consuming this contaminated fish in Egypt. Trace metals, including Ag,
      Al, Cd, Bo, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, St, V, Zn, and As, were determined in
      water, Tilapia nilotica, and sediments from the River Nile, Domiate branch,
      Egypt. Metal concentrations in fish of Al, Cd, Co, Fe, Mn, Pb, V, and Zn (mg/kg
      dry weight [dw]) and concentrations in sediment of Cd, Co, Cr, Cu, Mn, Ni, Pb, V,
      and Zn (mg/kg dw) were above the International Atomic Energy Agency (IAEA-407)
      levels. However, trace metals in river water were still at permissible levels for
      Egyptian standards. The hazard index (HI) of estimated metal mixtures for intake
      of Tilapia nilotica (23.37) demonstrated that intake resulted in higher
      noncarcinogenic risk. In conclusion, the overall problem of metal contamination
      in fish collected from the River Nile was more serious than postulated to occur
      in an industrialized and densely populated area. In the light of known risks to
      public health, environmental protection laws are needed in Egypt. 

PMID- 24283370
TI  - Short-term effects of fine particulate air pollution on ischemic stroke
      occurrence: a case-crossover study.
AB  - This study was undertaken to determine whether there was a correlation between
      fine particles (PM2.5) levels and hospital admissions for ischemic stroke (IS) in
      Taipei, Taiwan. Hospital admissions for IS and ambient air pollution data for
      Taipei were obtained for the period from 2006-2010. The relative risk of hospital
      admissions was estimated using a case-crossover approach, controlling for weather
      variables, day of the week, seasonality, and long-term time trends. For the
      single-pollutant model (without adjustment for other pollutants), increased
      admissions for IS were significantly associated with higher levels of PM2.5 on
      both warm days (>23 degrees C) and cool days (<23 degrees C), with an
      interquartile range rise associated with a 11% (95% CI = 8-14%) and 4% (95% CI =
      2-7%) elevation in admissions for IS, respectively. In the two-pollutant models,
      PM2.5 remained significantly increased after inclusion of sulfur dioxide (SO2) or
      ozone (O3) on both warm and cool days. This study provides evidence that higher
      levels of PM2.5 enhance the risk of hospital admissions for IS. 

PMID- 24283371
TI  - Gene expression and growth as indicators of effects of the BP Deepwater Horizon
      oil spill on spotted seatrout (Cynoscion nebulosus).
AB  - The BP Deepwater Horizon oil spill has great potential to negatively affect
      estuarine fish populations. In order to assess possible impacts of this event, a
      series of sublethal lab experiments were performed, using the economically and
      ecologically important species spotted seatrout (Cynoscion nebulosus). Larval and
      juvenile spotted seatrout were exposed to sublethal concentrations of high energy
      water accommodated fraction (HEWAF), chemically enhanced water accommodated
      fraction (CEWAF), or dispersant alone in an acute exposure. Response to exposure
      was evaluated with quantative polymerase chain reaction (qPCR) to examine
      expression of cytochrome P-4501A (CYP1A). Growth of larvae and juveniles over the
      duration of the experiment was measured as an index of physiological response.
      Our data showed that the different life stages respond differently to crude and
      dispersed oil, with larval spotted seatrout affected most by CEWAF, while
      juvenile spotted seatrout were affected to a greater extent by HEWAF. In both
      cases, the treatment with the highest CYP1A levels resulted in the greatest
      reductions in growth. 

PMID- 24283372
TI  - 31-day study of cobalt(II) chloride ingestion in humans: pharmacokinetics and
      clinical effects.
AB  - The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting
      cobalt (Co)-containing supplements up to 1400 MUg Co/d is unlikely to produce
      adverse health effects. However, the associated blood Co concentrations and
      safety of Co-containing dietary supplements have not been fully characterized.
      Thus, blood Co kinetics and a toxicological assessment of hematological and
      biochemical parameters were evaluated following Co dietary supplementation in 5
      male and 5 female volunteers who ingested approximately 1000 MUg Co/d (10-19 MUg
      Co/kg-d) as cobalt(II) chloride for a period of 31 d. Supplement intake was not
      associated with significant overt adverse events, alterations in clinical
      chemistries including blood counts and indicators of thyroid, cardiac, liver, or
      kidney functions, or metal sensitization. A non-clinically significant (<5%)
      increase in hemoglobin, hematocrit, and red blood cell (RBC) counts were observed
      in males but not females 1 wk after dose termination. Mean Co concentrations in
      whole blood/serum after 31 d of dosing were approximately two-fold higher in
      females (33/53 MUg/L) than in males (16/21 MUg/L). In general, steady-state
      concentrations of Co were achieved in whole blood and/or red blood cells (RBC)
      within 14-24 d. Temporal patterns of whole blood and serum Co concentrations
      indicated metal sequestration in RBC accompanied by slower whole blood clearance
      compared to serum. Data also indicated that peak whole blood Co concentrations up
      to 91.4 MUg/L were not associated with clinically significant changes in clinical
      chemistries. In addition, Co blood concentrations and systemic uptake via
      ingestion were generally higher in females. 

PMID- 24283373
TI  - Availability and access in modern obstetric care: a retrospective population
      based study.
AB  - OBJECTIVE: To assess the availability of obstetric institutions, the risk of
      unplanned delivery outside an institution and maternal morbidity in a national
      setting in which the number of institutions declined from 95 to 51 during 30
      years. DESIGN: Retrospective population-based, three cohorts and two cross
      sectional analyses. SETTING: Census data, Statistics Norway. The Medical Birth
      Registry of Norway from 1979 to 2009. POPULATION: Women (15-49 years), 2000 (n =
      1,050,269) and 2010 (n = 1,127,665). Women who delivered during the period 1979
      2009 (n = 1,807,714). METHODS: Geographic Information Systems software for travel
      zone calculations. Cross-table and multiple logistic regression analysis of
      change over time and regional differences. World Health Organization Emergency
      Obstetric and Newborn Care (EmOC) indicators. MAIN OUTCOME MEASURES: Proportion
      of women living outside the 1-hour travel zone to obstetric institutions. Risk of
      unplanned delivery outside obstetric institutions. Maternal morbidity. RESULTS:
      The proportion of women living outside the 1-hour zone for all obstetric
      institutions increased from 7.9% to 8.8% from 2000 to 2010 (relative risk, 1.1;
      95% confidence interval, 1.11-1.12), and for emergency obstetric care from 11.0%
      to 12.1% (relative risk, 1.1; 95% confidence interval, 1.09-1.11). The risk of
      unplanned delivery outside institutions increased from 0.4% in 1979-83 to 0.7% in
      2004-09 (adjusted odds ratio, 2.0; 95% confidence interval, 1.9-2.2). Maternal
      morbidity increased from 1.7% in 2000 to 2.2% in 2009 (adjusted odds ratio, 1.4;
      95% confidence interval, 1.2-1.5) and the regional differences increased.
      CONCLUSIONS: The availability of and access to obstetric institutions was reduced
      and we did not observe the expected decrease in maternal morbidity following the
      centralisation.

PMID- 24283374
TI  - Patterned fluoropolymer barriers for containment of organic solvents within paper
      based microfluidic devices.
AB  - In this study, we demonstrate for the first time the ability to pattern
      lipophobic fluoropolymer barriers for the incorporation of pure organic solvents
      as operating liquids within paper-based microfluidic devices. Our fabrication
      method involves replacing traditional wax barriers with fluoropolymer coatings by
      combining initiated chemical vapor deposition with inhibiting transition metal
      salt to pattern the polymer. Multiple techniques for patterning the transition
      metal salt are tested including painting, spray coating, and selective wetting
      through the use of a photoresist. The efficacy of the barrier coatings to contain
      organic solvents is found to be dependent on the conformality of the polymer
      deposited around the paper fibers. We demonstrate examples of the benefits
      provided by the containment of organic solvents in paper-based microfluidic
      applications including the ability to tune the separation of analytes by varying
      the operating solvent and by modifying the channel region of the devices with
      additional polymer coatings. The work exhibited in this paper has the potential
      to significantly expand the applications of paper-based microfluidics to include
      detection of water insoluble analytes. Additionally, the generality of the
      patterning process allows this technique to be extended to other applications
      that may require the use of patterned hydrophobic and lipophobic regions, such as
      biosensing, chemical detection, and optics. 

PMID- 24283375
TI  - Facial superficial granulomatous pyoderma.

PMID- 24283376
TI  - Mini-review: Staphylococcus epidermidis as the most frequent cause of nosocomial
      infections: old and new fighting strategies.
AB  - Staphylococcus epidermidis is nowadays regarded as the most frequent cause of
      nosocomial infections and indwelling medical device-associated infections. One of
      the features that contributes to the success of this microorganism and which is
      elemental to the onset of pathogenesis is its ability to form biofilms. Cells in
      this mode of growth are inherently more resistant to antimicrobials. Seeking to
      treat staphylococcal-related infections and to prevent their side effects, such
      as the significant morbidity and health care costs, many efforts are being made
      to develop of new and effective antistaphylococcal drugs. Indeed, due to its
      frequency and extreme resistance to treatment, staphylococcal-associated
      infections represent a serious burden for the public health system. This review
      will provide an overview of some conventional and emerging anti-biofilm
      approaches in the management of medical device-associated infections related to
      this important nosocomial pathogen. 

PMID- 24283377
TI  - ATR-FTIR detection of metal-sensitive structural changes in the light-harvesting
      1 reaction center complex from the thermophilic purple sulfur bacterium
      Thermochromatium tepidum.
AB  - Thermochromatium tepidum grows at the highest temperature among purple bacteria,
      and the light-harvesting 1 reaction center (LH1-RC) complex enhances the thermal
      stability by utilizing Ca(2+), although the molecular mechanism has yet to be
      resolved. Here, we applied perfusion-induced attenuated total reflection (ATR)
      Fourier transform infrared (FTIR) spectroscopy to highly purified LH1-RC
      complexes from Tch. tepidum and detected for the first time metal-sensitive fine
      structural changes involved in the enhanced thermal stability of this complex.
      The Tch. tepidum LH1-RC complex exhibited Sr(2+)/Ca(2+) ATR-FTIR difference bands
      that reflect changes in the polypeptide backbones and amino acid residues upon
      the replacement of native Ca(2+) with Sr(2+). The difference bands also appeared
      in the following Ca(2+)/Sr(2+) difference spectra with almost identical
      intensities but inverse signs, demonstrating that the structural changes induced
      by the metal exchange are fully reversible. In contrast, these ATR-FTIR signals
      were faintly detected in the mesophilic counterpart Allochromatium vinosum . A
      comparative analysis using LH1 complexes lacking the RCs strongly indicated that
      the metal-sensitive bands originate from polypeptide backbones and amino acid
      residues near the putative Ca(2+)-binding site at the C-terminal region of the
      Tch. tepidum LH1 complexes. Structural changes induced by Sr(2+) and Ba(2+)
      substitutions were essentially identical. However, Cd(2+) substitution exhibited
      unique structural modifications, which may be responsible for the severely
      deteriorated thermal stability of Cd(2+)-substituted complexes. Possible
      assignments for the present ATR-FTIR signals and their relation with the
      molecular mechanism of enhancing the thermal stability of Tch. tepidum LH1-RC
      proteins are discussed on the basis of the recent structural information on the
      Ca(2+)-binding site. 

PMID- 24283378
TI  - Electrochemical evidence for intermolecular proton-coupled electron transfer
      through a hydrogen bond complex in a p-phenylenediamine-based urea. Introduction
      of the "wedge scheme" as a useful means to describe reactions of this type.
AB  - The electrochemistry of several p-phenylenediamine derivatives, in which one of
      the amino groups is part of an urea functional group, has been investigated in
      methylene chloride and acetonitrile. The ureas are abbreviated U(R)R', where R'
      indicates the substituent on the N that is part of the phenylenediamine redox
      couple and R indicates the substituent on the other urea N. Cyclic voltammetry
      and UV-vis spectroelectrochemical studies indicate that U(Me)H and U(H)H undergo
      an apparent 1e(-) oxidation that actually corresponds to 2e(-) oxidation of half
      the ureas to a quinoidal-diimine cation, U(R)(+). This is accompanied by proton
      transfer to the other half of the ureas to make the electroinactive cation
      HU(R)H(+). This explains the observed irreversibility of the oxidation of U(Me)H
      in both solvents and U(H)H in acetonitrile. However, the oxidation of U(H)H in
      methylene chloride is reversible at higher concentrations and slower scan rates.
      Several lines of evidence suggest that the most likely reason for this is the
      accessibility of a H-bond complex between U(H)(+) and HU(H)H(+) in methylene
      chloride. Reduction of the H-bond complex occurs at a less negative potential
      than that of U(H)(+), leading to reversible behavior. This conclusion is strongly
      supported by the appearance of a more negative reduction peak at lower
      concentrations and faster scan rates, conditions in which the H-bond complex is
      less favored. The overall reaction mechanism is conveniently described by a
      "wedge scheme", which is a more general version of the square scheme typically
      used to describe redox processes in which proton transfer accompanies electron
      transfer. 

PMID- 24283379
TI  - Exploring own-age biases in deception detection.
AB  - The present study explored own-age biases in deception detection, investigating
      whether individuals were more likely to trust those in their own-age group.
      Younger and older participants were asked to detect deceit from videos of younger
      and older speakers, rating their confidence in each decision. Older participants
      showed an own-age bias: they were more likely to think that deceptive speakers of
      their own age, relative to younger speakers, were telling the truth. Older
      participants were also more confident in their judgements of own-age, relative to
      other-age, speakers. There were no own-age biases for younger participants. In a
      subsequent (apparently unrelated) task, participants were asked to rate the
      trustworthiness of the speakers. Both age groups of participants trusted younger
      speakers who had previously told the truth more compared to those who had lied.
      This effect was not found for older speakers. These findings are considered in
      relation to the in-group/out-group model of social cognition and common
      stereotypical beliefs held about younger and older adults. 

PMID- 24283380
TI  - On the anisotropy of van der Waals atomic radii of O, S, Se, F, Cl, Br, and I.
AB  - The Cambridge Structural Database (CSD) was used to obtain flattening factors to
      describe the overall anisotropy of nonbonding van der Waals (vdW) contacts
      between several main group elements. The method for obtaining the flattening
      factors is based on a novel minimization process. Results show that the vdW
      contact distances are significantly dependent on the environment and the
      orientations of the surrounding covalently bonded atoms: head-on vdW contacts are
      generally shorter than sideways contacts in overall agreement with earlier
      results by Nyburg and Faerman (Acta Crystallogr., Sect. B: Struct. Sci. 1985, 41,
      274-279). With the exception of Se, we find flattening factors that are somewhat
      smaller than those found earlier. High-level ab initio quantum chemical
      calculations using Ar and Ne as a probe also confirm the flattening effect and
      its dependency on the environment. A dozen popular long-range corrected and
      dispersion supplemented density functionals are compared with the CCSD(T) data.
      While several of them perform quite poorly, four DFT-D methods, especially B3LYP
      GD3BJ, provided vdW flattening similar to those found by the CCSD(T) theory and
      experiment. 

PMID- 24283381
TI  - The use of dietary supplements and their association with blood pressure in a
      large Midwestern cohort.
AB  - BACKGROUND: There have been numerous studies assessing the association of diet
      and blood pressure but little is known about the association between less
      commonly used nutritional supplements and blood pressured. The purpose of this
      study was to quantify the use of dietary supplements and their potential
      association with blood pressure in a large population-based cohort of adults in
      the Midwest. METHODS: The Personalized Medicine Research Project cohort was the
      population source for the current study. The current study includes subjects with
      Dietary History Questionnaire (DHQ) data available as well as at least one
      clinical blood pressure measurement recorded in their electronic medical record.
      After excluding extreme outlying measurements, median systolic and diastolic
      blood pressure measurements were calculated for each individual and were compared
      for subjects who did and did not report taking one of a list of 37 different
      supplements listed on the DHQ more than once per week over the previous 12
      months. RESULTS: 9,732 subjects had both blood pressure and DHQ data available.
      They ranged in age from 18 to 98 years (mean 56 years) and 3,625 (37%) were male.
      Nine of 37 supplements showed evidence for association with blood pressure:
      coenzyme Q10, fish oil, iron, bilberry, echinacea, evening primrose oil, garlic,
      goldenseal and milk thistle. With the exception of the mineral iron, mean
      systolic and diastolic blood pressures were higher for users of the specific
      supplements than non-users. CONCLUSIONS: These results should not be interpreted
      as causal, nor can the direction of the association be assumed to be correct
      because the temporality of the association is unknown. We hope the observed
      significant associations will foster future research to evaluate blood pressure
      effects of dietary supplements.

PMID- 24283382
TI  - Zinc-finger BED domain-containing 3 (Zbed3) is a novel secreted protein
      associated with insulin resistance in humans.
AB  - OBJECTIVES: Genome-wide association studies (GWAS) have shown that Zbed3 is
      associated with T2DM. To date, no report has demonstrated a relationship between
      Zbed3 and insulin resistance in humans, however. The purpose of this study was to
      determine whether the Zbed3 protein is secreted and identify any associations
      between Zbed3 and insulin resistance in cross-sectional and interventional
      studies. METHODS: We found that Zbed3 protein was secreted in an in vitro
      secretion study. Plasma Zbed3 levels were determined in an ELISA and were
      compared with various parameters related to insulin resistance in subjects with
      NGT, IGT and nT2DM. EHC was performed in healthy subjects. Real-time PCR and
      Western blotting were used to assess the mRNA and protein expression of Zbed3.
      RESULTS: Zbed3 was detected in an analysis of in vitro secretion in both
      conditioned medium and lysates of HEK-293T cells transfected with an
      overexpressed vector. In a clinical study, there were significantly higher levels
      of circulating Zbed3 in IGT and nT2DM relative to NGT. Zbed3 levels were
      positively correlated with BMI, WHR, FAT%, blood pressure, FBG, TG, HbA1c, FIns
      and HOMA-IR and inversely correlated with HDL-C. Increasing levels of Zbed3 were
      independently associated with IGT and T2DM. Zbed3 mRNA and protein in muscle and
      fat were significantly elevated in both db/db mice and T2DM patients. Moreover,
      there was a concentration-dependent effect of glucose on Zbed3 release, whereas
      insulin exhibited an inhibitory effect on Zbed3 levels. Zbed3 suppressed insulin
      induced IR and Akt phosphorylation. CONCLUSIONS: These results suggest that the
      Zbed3 protein may be a cytokine associated with insulin resistance in humans that
      is influenced by glucose and insulin levels.

PMID- 24283383
TI  - Challenges in machine perfusion preservation for liver grafts from donation after
      circulatory death.
AB  - Donation after circulatory death (DCD) is a promising solution to the critical
      shortage of donor graft tissue. Maintaining organ viability after donation until
      transplantation is essential for optimal graft function and survival. To date,
      static cold storage is the most widely used form of preservation in clinical
      practice. However, ischemic damage present in DCD grafts jeopardizes organ
      viability during cold storage, and whether static cold storage is the most
      effective method to prevent deterioration of organ quality in the increasing
      numbers of organs from DCD is unknown. Here we describe the historical background
      of DCD liver grafts and a new preservation method for experimental and clinical
      transplantation. To prevent ischemia-reperfusion injury in DCD liver grafts, a
      hypothermic machine perfusion (HMP) technique has recently been developed and may
      be superior to static cold preservation. We present evidence supporting the need
      for improving liver perfusion performance and discuss how doing so will benefit
      liver transplantation recipients. 

PMID- 24283384
TI  - MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates
      tumor invasiveness and poor prognosis.
AB  - Gastric cancer (GC) develops through deregulation of gene expression and
      accumulation of epigenetic abnormalities, leading to tumor cell acquisition of
      malignant features. MicroRNAs (miRNAs) play a critical role in cancer development
      where they can act as oncogenes or oncosuppressors. To identify miRNAs that are
      associated with some clinicopathologic features of GC and/or participate in tumor
      progression, miRNA expression in 20 GC tissues and five corresponding non
      neoplastic gastric mucosa was examined by miRNA microarray. Oligonucleotide array
      analysis was carried out for miRNA target prediction. The functions of candidate
      miRNAs and their target genes were also analyzed by quantitative RT-PCR, Western
      blotting, reporter gene assay, and cell invasion assay. Comparison of miRNA
      expression profiles revealed that downregulation of miR-148a was identified in
      most of the GC tissues. Downregulation of miR-148a was significantly correlated
      with an advanced clinical stage, lymph node metastasis, and poor clinical
      outcome. Custom oligonucleotide array analysis revealed that MMP7 expression was
      markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be
      a direct and functional target of miR-148a, participating in cell invasion. These
      results suggest that miR-148a contributes to the maintenance of homeostasis in
      normal stomach tissue and plays an important role in GC invasion by regulating
      MMP7 expression. 

PMID- 24283385
TI  - Isotretinoin and mental health in adolescents: Australian consensus.
AB  - Acne is a common condition among adolescents and has the potential to negatively
      impact on the psychological well-being of those who suffer from it. In
      particular, depression and suicidal ideation are more common in adolescents with
      acne. Successful treatment of acne can improve the quality of life and reduce
      levels of anxiety and depression in these individuals. The current treatment of
      choice for severe or refractive acne is isotretinoin, a retinoid. While the
      possible causal association between isotretinoin and mental illness remains a
      controversial topic, a recent systematic review has presented evidence to support
      this relationship. In light of this evidence, a group of dermatologists and
      psychiatrists have collaborated to develop these recommendations to aid the safe
      prescribing of isotretinoin in adolescents. These clinical suggestions are aimed
      at practitioners in both disciplines to increase awareness of the current
      evidence in support of the association between isotretinoin and adolescent
      depression. 

PMID- 24283386
TI  - Standing laparoscopic inguinal hernioplasty using cyanoacrylate for preventing
      recurrence of acquired strangulated inguinal herniation in 10 stallions.
AB  - OBJECTIVE: To describe a technique for standing inguinal hernioplasty in horses
      using cyanoacrylate glue, and to evaluate its effect on prevention of recurrent
      inguinal herniation in stallions that had previous acquired strangulated inguinal
      hernia (SIH). STUDY DESIGN: Case series. ANIMALS: Stallions (n = 10) with a
      history of SIH. METHODS: Hernioplasty was performed in standing horses using 4
      laparoscopic portals. The mesorchium was retracted caudomedially using Babcock
      forceps. A flexible polyethylene extension tube was introduced through the sheath
      of a laparoscopic needle and n-butyl-2-cyanoacrylate (2 mL) was injected into the
      inguinal canal including its margins while a 2nd Babcock forceps prevented deep
      ventral diffusion of the cyanoacrylate. The craniolateral parts of the vaginal
      ring were compressed until full adhesion between the visceral and parietal walls
      was achieved. In 2 horses, the lateral part of the vaginal ring was sutured
      before gluing. A contralateral approach was used to check the caudomedial part of
      the vaginal ring. RESULTS: No recurrence (1-4 years) of inguinal hernia was
      reported. No major complications occurred and cosmetic outcome was excellent. All
      horses were used for their intended purpose and 7 horses being used as breeding
      stallions remained fertile. CONCLUSION: Standing inguinal hernioplasty using
      cyanoacrylate seems to provide efficient and secure closure of the vaginal ring
      in stallions.

PMID- 24283387
TI  - Novel enzymatic assay predicts minoxidil response in the treatment of
      androgenetic alopecia.
AB  - Topical minoxidil is the most common drug used for the treatment of androgenetic
      alopecia (AGA) in men and women. Although topical minoxidil exhibits a good
      safety profile, the efficacy in the overall population remains relatively low at
      30-40%. To observe significant improvement in hair growth, minoxidil is typically
      used daily for a period of at least 3-4 months. Due to the significant time
      commitment and low response rate, a biomarker for predicting patient response
      prior to therapy would be advantageous. Minoxidil is converted in the scalp to
      its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We
      hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with
      minoxidil response for the treatment of AGA. Our preliminary retrospective study
      of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in
      predicting minoxidil treatment response for AGA. A larger prospective study is
      now under way to further validate this novel assay. 

PMID- 24283388
TI  - Prevention of polymorphic light eruption by oral administration of a nutritional
      supplement containing lycopene, beta-carotene, and Lactobacillus johnsonii:
      results from a randomized, placebo-controlled, double-blinded study.
AB  - BACKGROUND: Polymorphic light eruption (PLE) is the most common photodermatosis.
      Little is known about the efficacy of systemic photoprotection provided by
      nutritional supplements in PLE patients. PURPOSE: The purpose of this study was
      to assess efficacy of nutritional supplement containing lycopene, beta-carotene,
      and Lactobacillus johnsonii to diminish skin lesions induced by
      'photoprovocation' testing in PLE patients. METHODS: In this randomized, placebo
      controlled, double-blinded study, 60 PLE patients were supplemented with the
      nutritional supplement or placebo. For inducing skin lesions, patient skin was
      exposed to single daily doses of 100 J/cm2 ultraviolet A1 (UVA1) for two
      consecutive days. Skin lesions were evaluated using a PLE score. Skin biopsies
      were taken before and after supplementation from unexposed and exposed skin, and
      intercellular adhesion molecule 1 (ICAM-1) mRNA expression was assessed by real
      time polymerase chain reaction. RESULTS: Prior to supplementation, skin lesions
      were induced in all patients with comparable PLE scores. After 12 weeks, intake
      of the supplement significantly reduced the PLE score after one exposure as
      compared with patients taking placebo (P<0.001). After two exposures, these
      differences were no longer significant. At a molecular level, the development of
      skin lesions was associated with an increased expression of ICAM-1 mRNA, which
      was significantly reduced after supplementation (P=0.022), but not with placebo.
      CONCLUSION: The nutritional supplement provides protection against the
      development of UVA-induced PLE lesions at clinical and molecular levels.

PMID- 24283389
TI  - Functional analysis of the N-terminal region of an essential histidine kinase,
      Hik2, in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Histidine kinases are sensory proteins involved in the perception of
      environmental changes. Here, we characterized one of three essential histidine
      kinases, Hik2, in the cyanobacterium Synechocystis sp. PCC 6803 by constructing a
      fused sensor, Hik2n-Hik7c, which has the signal input domain of Hik2 and the
      kinase domain of the phosphate-deficiency sensor Hik7. The coding region of the
      hik7 gene was replaced with the fused sensor to evaluate the signalling activity
      in vivo as the activity of alkaline phosphatase (AP), which is regulated by Hik7.
      Cells expressing Hik2n-Hik7c had weak AP activities under standard growth
      conditions. Saline stress by NaCl induced AP activity in a dose-dependent manner.
      Analysis of the effects of several salt compounds on induction of AP activity
      indicated that Hik2n-Hik7c responded to Cl- concentration. Amino acid
      substitution in the signal input domain of Hik2 resulted in loss of this
      responsiveness. These results suggest that the signal input domain of Hik2
      responds to environmental Cl- concentration in Synechocystis.

PMID- 24283390
TI  - The role of perceived well-being in the family, school and peer context in
      adolescents' subjective health complaints: evidence from a Greek cross-sectional
      study.
AB  - BACKGROUND: During adolescence children are usually confronted with an expanding
      social arena. Apart from families, schools and neighbourhoods, peers, classmates,
      teachers, and other adult figures gain increasing importance for adolescent socio
      emotional adjustment. The aim of the present study was to investigate the extent
      to which Greek adolescents' perceived well-being in three main social contexts
      (family, school and peers) predicted self-reported Subjective Health Complaints.
      METHODS: Questionnaires were administered to a Greek nation-wide, random, school
      based sample of children aged 12-18 years in 2003. Data from 1.087 adolescents
      were analyzed. A hierarchical regression model with Subjective Health Complaints
      as the outcome variable was employed in order to i) control for the effects of
      previously well-established demographic factors (sex, age and subjective economic
      status) and ii) to identify the unique proportion of variance attributed to each
      context. Bivariate correlations and multicollinearity were also explored.
      RESULTS: As hypothesized, adolescents' perceived well-being in each of the three
      social contexts appeared to hold unique proportions of variance in self-reported
      Subjective Health Complaints, after controlling for the effects of sex, age and
      subjective economic status. In addition, our final model confirmed that the
      explained variance in SHC was accumulated from each social context studied. The
      regression models were statistically significant and explained a total of
      approximately 24% of the variance in Subjective Health Complaints. CONCLUSIONS:
      Our study delineated the unique and cumulative contributions of adolescents'
      perceived well-being in the family, school and peer setting in the explanation of
      Subjective Health Complaints. Apart from families, schools, teachers and peers
      appear to have a salient role in adolescent psychosomatic adjustment. A thorough
      understanding of the relationship between adolescents' Subjective Health
      Complaints and perceived well-being in their social contexts could not only lead
      to more effective tailored initiatives, but also to promote a multi- and inter
      disciplinary culture in adolescent psychosomatic health.

PMID- 24283391
TI  - Transcutaneous electrical nerve stimulation (TENS) for pain control after vaginal
      delivery and cesarean section.
AB  - OBJECTIVE: The present study aims to determine the efficiency and reliability of
      transcutaneous electrical nerve stimulation (TENS) in the management of pain
      related with uterine contractions after vaginal delivery and the pain related
      with both abdominal incision uterine contractions after cesarean section.
      METHODS: A hundred healthy women who underwent cesarean section under general
      anesthesia were randomly assigned to the placebo group (Group 1) or the TENS
      group (Group 2), while 100 women who delivered by vaginal route without
      episiotomy were randomized into the placebo group (Group 3) or the TENS group
      (Group 4). RESULTS: The patients in Group 2 had statistically lower visual analog
      scale (VAS) and verbal numerical scale (VNS) scores than the patients in Group 1
      (p < 0.001 for both). The patients in Group 4 had statistically lower VAS and VNS
      scores than the patients in Group 3 (p = 0.022 and p = 0.005, respectively). The
      analgesic requirement at the eighth hour of cesarean section was significantly
      lower in the patients who were treated with TENS (p = 0.006). The need for
      analgesics at the eighth hour of vaginal delivery was statistically similar in
      the patients who were treated with TENS and the patients who received placebo (p
      = 0.830). CONCLUSION: TENS is an effective, reliable, practical and easily
      available modality of treatment for postpartum pain.

PMID- 24283392
TI  - Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles.
AB  - Gemcitabine-loaded solid lipid nanoparticles (SLNs) were produced by double
      emulsification technique using stearic acid as lipid, soy lecithin as surfactant
      and sodium taurocholate as cosurfactant. Prepared nanoparticles are characterized
      for particle size and surface morphology using scanning electron microscopy
      (SEM). Particle yield, entrapment efficiency and zeta potential were also
      determined. In-vitro release studies were performed in phosphate-buffered saline
      (PBS) pH 7.4 using metabolic shaker. The formulation F6 with maximum entrapment
      efficiency 72.42% and satisfactory in-vitro release was selected. In-vivo tissue
      distribution to liver, spleen, lung, heart and kidneys of optimized formulation
      followed by stability study under specific conditions were also determined. This
      investigation has shown preferential drug targeting to liver followed by spleen,
      lungs, kidneys and heart. Stability studies showed no significant change in the
      particle size followed with very slight decrease in entrapment efficiency at 25
      +/- 2  degrees C/60 +/- 5% RH over a period of three months.

PMID- 24283393
TI  - Atomic-layer-deposition oxide nanoglue for sodium ion batteries.
AB  - Atomic-layer-deposition (ALD) coatings have been increasingly used to improve
      battery performance. However, the electrochemical and mechanistic roles remain
      largely unclear, especially for ALD coatings on electrodes that undergo
      significant volume changes (up to 100%) during charging/discharging. Here we
      investigate an anode consisting of tin nanoparticles (SnNPs) with an ALD-Al2O3
      coating. For the first time, in situ transmission electron microscopy unveiled
      the dynamic mechanical protection of the ALD-Al2O3 coating by coherently
      deforming with the SnNPs under the huge volume changes during
      charging/discharging. Battery tests in coin-cells further showed the ALD-Al2O3
      coating remarkably boosts the cycling performance of the Sn anodes, comparing
      with those made of bare SnNPs. Chemomechanical simulations clearly revealed that
      a bare SnNP debonds and falls off the underlying substrate upon charging, and by
      contrast the ALD-Al2O3 coating, like ion-conductive nanoglue, robustly anchors
      the SnNP anode to the substrate during charging/discharging, a key to improving
      battery cycle performance. 

PMID- 24283394
TI  - Biomarker measurements of prenatal exposure to polychlorinated biphenyls (PCB) in
      umbilical cord blood from postpartum Hispanic women in Brownsville, Texas.
AB  - Biomarkers of polychlorinated biphenyls (PCB) were measured in both maternal and
      umbilical cord blood from 35 pregnant Hispanic women living in Brownsville, TX.
      Gas chromatography with an electron capture detector (GC/ECD) was used to analyze
      for 22 PCB analytes. Results indicated that both pregnant mothers and their
      fetuses were exposed to a variety of PCB at relatively low levels (<= 0.2 ng/ml),
      and that concentrations in maternal and cord blood were similar. Concentrations
      of total PCB (sum or all PCB congeners) averaged more than 2.5 ng/ml, with
      highest values exceeding 3 ng/ml. Although health implications are uncertain,
      reports in the literature of PCB-related health effects raise concerns about
      possible future health consequences, especially obesity and diabetes, in this
      potentially vulnerable population.

PMID- 24283395
TI  - The stability of citrate-capped silver nanoparticles in isotonic glucose solution
      for intravenous injection.
AB  - Citrate-capped silver nanoparticles (AgNP) are widely used in industry, consumer
      products, and medical appliances. However, information on the environmental
      toxicity and human health is not comprehensive. Further, the physicochemical
      properties of AgNP make it difficult to test toxicity, as nanosized particles,
      due to their size, may increase by aggregation or agglomeration in some
      administration vehicles. In this study, stability of AgNP was investigated in
      different types of isotonic solutions, which is important for in vitro testing or
      toxicokinetic studies using intravenous (iv) injection. Size, morphology, zeta
      potential, and ion formation were investigated in isotonic solutions for the
      physicochemical characterization of AgNP. Aggregation and precipitation of AgNP
      were observed in phosphate-buffered saline or 0.9% NaCl, while AgNP were stable
      without aggregation or precipitation in 5% glucose in isotonic solution. The
      average size of AgNP in 5% glucose was approximately 10 nm at different
      temperatures of 10, 25, or 36 degrees C and at varying concentrations from 10 to
      1000 ppm. It is noteworthy that this is almost the same size distribution as that
      in the water-based suspension of AgNP supplied by the manufacturer. Zeta
      potential ranged from -40 to -60 mV, suggesting that the repulsion forces of AgNP
      are not disturbed to a sufficient degree to aggregate while osmolarity is in the
      isotonic range of 290 +/- 10 mOsm/kg in 5% glucose solution. Data suggest that
      AgNP in a 5% glucose solution may be used in the toxicity test via iv injection
      without adverse consequences in blood. 

PMID- 24283396
TI  - Toxicokinetic differences and toxicities of silver nanoparticles and silver ions
      in rats after single oral administration.
AB  - Blood levels, tissue distributions, and excretion of silver (Ag) were measured in
      male Sprague-Dawley rats (n = 5) up to 24 h after a single oral administration of
      silver nanoparticles (AgNP) and silver ions (Ag(+)), respectively. The AUC24hr of
      Ag(+) was 3.81 +/- 0.57 MUg/d/ml when rats were treated with a single dose of 20
      mg/kg, whereas that of AgNP was 1.58 +/- 0.25 MUg/d/ml. Tissue distribution of Ag
      in liver, kidneys, and lungs was higher when Ag(+) was administered compared to
      AgNP. Orally administered AgNP were predominantly excreted through feces,
      suggesting low bioavailability. Death or body weight changes were not observed in
      the Ag(+)- or AgNP-treated groups. However, decreased red blood cell counts,
      hematocrit, and hemoglobin were found in the Ag(+)-treated groups, while
      increased platelet counts and mean platelet volume were noted in the AgNP-treated
      rats. A serum biochemical analysis showed that aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT) rose significantly following Ag(+) treatment
      (20 mg/kg). AgNP treatment (2 or 20 mg/kg) also elevated AST, whereas
      infiltration of mononuclear cells with liver necrosis was found only in the 20
      mg/kg Ag(+)-treated animals. 

PMID- 24283397
TI  - Uranium mine proximity, immune function, and Helicobacter pylori infection in
      Tajikistan.
AB  - Tajikistan is a country with numerous abandoned uranium mines and individuals
      residing in close proximity to these sites. Inspection of one of these sites next
      to the town of Taboshar revealed uncontrolled waste with elevated radiation
      levels. Convenience samples of subjects likely to have been exposed to uranium
      mining (i.e., combined living near wastes and former miners) and unexposed
      subjects (living far from mines and never working in mining) were recruited.
      There was a higher prevelance of Helicobacter pylori (H. pylori) infection among
      the exposed and there were significantly more virulent infections involving CagA.
      Histolological examination of the stomach showed more gastric atrophy in the
      exposed group. Exposed individuals also had lower percentage of T lymphocytes,
      fewer T-helper cells, significant imbalance in the immunoregulation index, and
      significantly higher levels of cytotoxic lymphocytes. There were also reduced
      levels of immunoglobulin (Ig) M and IgG in the exposed group. These findings are
      consistent with adverse effects on immune functioning that might increase the
      rate of development of infectious disease, However, lack of control for
      confounding factors and lack of individual exposure assessment limit conclusions
      that can be drawn. Further research that addresses these limitations of this
      analysis is needed. 

PMID- 24283399
TI  - Influence of exercise intensity on systemic oxidative stress and antioxidant
      capacity.
AB  - The aim of the current study was to examine the influence of exercise intensity
      on systemic oxidative stress (OS) and endogenous antioxidant capacity. Non
      smoking, sedentary healthy adult males (n = 14) participated in two exercise
      sessions using an electronically braked cycle ergometer. The first session
      consisted of a graded exercise test to determine maximal power output and oxygen
      consumption (VO(2max)). One week later, participants undertook 5-min cycling
      bouts at 40%, 55%, 70%, 85% and 100% of VO(2max), with passive 12-min rest
      between stages. Measures of systemic OS reactive oxygen metabolites (dROM),
      biological antioxidant potential (BAP), heart rate (HR), VO(2), blood lactate and
      rating of perceived exertion were assessed at rest and immediately following each
      exercise stage. Significant (P<0.05) differences between exercise bouts were
      examined via repeated measures ANOVA and post hoc pairwise comparisons with
      Bonferroni correction. Increasing exercise intensity significantly augmented HR
      (P<0.001), VO(2) (P<0.001), blood lactate (P<0.001) and perceived exertion
      (P<0.001) with no significant effect on dROM levels compared with resting values.
      In contrast, increasing exercise intensity resulted in significantly (P<0.01)
      greater BAP at 70% (2427 +/- 106), 85% (2625 +/- 121) and 100% (2651 +/- 92) of
      VO(2max) compared with resting levels (2105 +/- 57 MUmol Fe(2+)/L). The current
      results indicate that brief, moderate-to-high-intensity exercise significantly
      elevates endogenous antioxidant defences, possibly to counteract increased levels
      of exercise-induced reactive oxygen species. Regular moderate-to-high-intensity
      exercise may protect against chronic OS associated diseases via activation, and
      subsequent upregulation of the endogenous antioxidant defence system.

PMID- 24283398
TI  - Smoking-related cotinine levels and host responses in chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Smoking has been reported to increase the risk of
      periodontal disease by disrupting the balance of immune responses and tissue
      repair processes; however, this risk varies among smokers. Cotinine levels in
      saliva are routinely used to measure the level of smoking, and reflect the
      quantity of nicotine, and other smoking-related xenobiotics that challenge host
      systems. This study delineated characteristics of inflammatory mediators in
      saliva and serum antibody responses to both periodontal pathogens and commensal
      bacteria in smokers as they related to cotinine levels. MATERIALS AND METHODS:
      This case-control study (n = 279) examined salivary inflammatory mediator
      responses [interleukin (IL)-1beta, IL-10, prostaglandin E2, myeloperoxidase and
      plasminogen activator inhibitor-1], and serum IgG antibody responses to three
      periodontal pathogens (Aggregatibacter actinomyce-temcomitans, Porphyromonas
      gingivalis, Treponema denticola) and five commensal oral microorganisms
      (Veillonella parvula, Streptococcus sanguis, Prevotella loescheii, Actinomyces
      naeslundii, Capnocytophaga ochracea). RESULTS: The patients were stratified into
      health (n = 30), gingivitis (n = 55) and periodontitis (n = 184); cotinine levels
      correlated with reported smoking habits in health, less so with gingivitis, and
      were not correlated in periodontitis. Of the inflammatory mediators/acute phase
      proteins, only IL-1beta levels were positively associated (p < 0.001) with the
      pack years and cotinine levels. As might be predicted, patients with
      periodontitis smoked more (p < 0.001) and had higher levels of cotinine. IL-1beta
      and antibody to A. actinomycetemcomitans, P. gingivalis and T. denticola were
      significantly higher in the patients with periodontitis than either patients with
      gingivitis or who were healthy. CONCLUSIONS: Generally, antibody to the pathogens
      and commensals was lower with decreased cotinine levels. Smoking exacerbated
      differences in both inflammatory mediators and three antibody in periodontal
      disease compared to healthy subjects.

PMID- 24283400
TI  - Temporal dissociations within the core recollection network.
AB  - We investigated whether time courses of fMRI BOLD activity in recollection
      sensitive brain regions varied according to the time over which recollected
      information was maintained. Human subjects studied word-picture pairs and were
      subsequently tested with studied and unstudied pictures during a scanned test
      phase. The test requirement was to judge whether each picture was old or new and,
      if old, to retrieve its study associate and hold it in mind until a response cue
      appeared. The interval between the test item and cue varied between two and eight
      seconds. Separate responses were required when items were deemed new or the
      associate was not retrieved. Whereas recollection-related activity in the
      posterior cingulate, medial temporal, and medial prefrontal cortices was
      transient and unrelated to the maintenance interval, activity in the left
      anterior angular gyrus (aLAG) tracked the interval. Thus, as in a prior study,
      recollection-sensitive regions could be temporally dissociated.

PMID- 24283401
TI  - Electronic, optical, and computational studies of a redox-active
      napthalenediimide-based coordination polymer.
AB  - The new one-dimensional coordination framework (Zn(DMF)NO3)2(NDC)(DPMNI), where
      NDC = 2,6-naphthalenedicarboxylate and DPMNI = N,N'-bis(4-pyridylmethyl)-1,4,5,8
      naphthalenetetracarboxydiimide, which has been crystallographically
      characterized, exhibits two redox-accessible states due to the successive
      reduction of the naphthalenediimide (NDI) ligand core. Solid-state
      electrochemical and vis-near-IR spectroelectrochemical measurements coupled with
      density functional theory (DFT) calculations enabled the origins of the optical
      transitions in the spectra of the monoradical anion and dianion states of the
      material to be assigned. Electron paramagnetic resonance (EPR) spectroscopy
      revealed that the paramagnetic radical anion state of the DPMNI core could be
      accessed upon broad-spectrum white light irradiation of the material, revealing a
      long-lived excited state, possibly stabilized by charge delocalization which
      arises from extensive pi-pi* stacking interactions between alternating NDC and
      NDI aromatic cores which are separated by a distance of 3.580(2) A. 

PMID- 24283402
TI  - What are the safety risks for patients undergoing treatment by multiple
      specialties: a retrospective patient record review study.
AB  - BACKGROUND: If multiple medical specialties are involved in treatment there is a
      danger of increasing risks to patient safety. This is due to the need for greater
      co-ordination and communication with other specialties, less emergency cover for
      individual sub-specialties, and a drop in general care and the overview of care.
      This study aims to determine if the number of medical specialties treating a
      patient is associated with the risk of experiencing harm during hospital
      admission. METHODS: We performed a retrospective patient record review study
      using a stratified sample of 20 hospitals in the Netherlands. In each hospital
      200 patient admissions were included. We related the occurrence of preventable
      adverse events and non-preventable adverse events to the number of specialties
      treating a patient through a stepwise multilevel logistic regression analysis.
      RESULTS: Compared to patients treated by only one specialty, patients treated by
      three or more specialties had an odds ratio of experiencing an adverse event of
      3.01 (95% CI 2.09 to 4.34), and an odds ratio of experiencing a preventable
      adverse event of 2.78 (95% CI 1.77 to 4.37). After adding characteristics related
      to the patient and the type of health care, the odds ratio for non-preventable
      adverse events decreased to 1.46 (95% CI 0.95 to 2.26), and for preventable
      adverse events to 2.31 (95% CI 1.40 to 3.81). There were no large differences
      found between the groups relating to the causes of preventable adverse events.
      However, in patients treated by three or more specialties, the greater number of
      preventable adverse events was related to the diagnostic process. CONCLUSIONS:
      The more specialties treating a patient the greater the risk of an adverse event.
      This finding became more pronounced for preventable adverse events than for non
      preventable adverse events after corrections for the characteristics of the
      patient and their health care. This study highlights the importance of taking the
      number of specialties treating a patient into account. More research is needed to
      gain insight into the underlying causes of inadequate care when multiple
      specialties are required to treat a patient. This could result in appropriate
      solutions resulting in improvements to care.

PMID- 24283403
TI  - Study on the TOC concentration in raw water and HAAs in Tehran's water treatment
      plant outlet.
AB  - A sampling has been undertaken to investigate the variation of haloacetic acids
      formation and nature organic matter through 81 samples were collected from three
      water treatment plant and three major rivers of Tehran Iran. Changes in the total
      organic matter (TOC), ultraviolet absorbance (UV254), specific ultraviolet
      absorbance (SUVA) were measured in raw water samples. Haloacetic acids
      concentrations were monitored using a new static headspace GC-ECD method without
      a manual pre-concentration in three water treatment plants. The average
      concentration of TOC and HAAs in three rivers and three water treatment plants in
      spring, summer and fall, were 4, 2.41 and 4.03 mg/L and 48.75, 43.79 and 51.07
      MUg/L respectively. Seasonal variation indicated that HAAs levels were much
      higher in spring and fall. 

PMID- 24283404
TI  - Vulval papules: a case for diagnosis.
AB  - You are asked to examine a 68-year-old woman with a 3-year history of multiple
      bilateral and largely asymptomatic white papules on her labia majora. Based on
      the history and photographs, what is your diagnosis? 

PMID- 24283405
TI  - Effects of iodine on the relaxation dynamics of a photoexcited I(-)(H(2)O)(4)
      cluster.
AB  - The Born-Oppenheimer molecular dynamics are used to examine the relaxation
      dynamics of the charge-transfer-to-solvent (CTTS) photoexcited electron in I(
      )(H2O)4. The dynamics are initiated from the C1' cluster configuration, which
      contains a dangling water molecule. The iodine atom is found to exert a repulsive
      force on the photoexcited electron at the beginning but an attractive force at
      later times of the simulation. This dual repulsion-and-attraction role of the
      iodine atom is found to be dependent on the ratio of the iodine-electron distance
      to the radius of gyration of the excited electron, d/r. In the region of d/r <
      ~0.8, the iodine exerts an exclusion-repulsion force on the excited electron.
      Conversely, for values of d/r > ~1.0, the iodine can exert an attractive force on
      the excited electron due to the induced dipole moment of iodine. However, at
      large iodine-electron distances, the iodine-electron interaction becomes very
      weak, and as a result, this attractive force is expected to fade away. Due to the
      heavy mass of the iodine atom, the evolution of the iodine-electron distance is
      driven by the motion of solvent molecules and not iodine itself. The dangling
      water molecules and the dipolar field of water molecules are also important in
      the solvent dynamics. The influence of temperature on the iodine effects and the
      experimental implications of the findings are also discussed. 

PMID- 24283406
TI  - Genome wide profiling of Azospirillum lipoferum 4B gene expression during
      interaction with rice roots.
AB  - Azospirillum-plant cooperation has been mainly studied from an agronomic point of
      view leading to a wide description of mechanisms implicated in plant growth
      promoting effects. However, little is known about genetic determinants implicated
      in bacterial adaptation to the host plant during the transition from free-living
      to root-associated lifestyles. This study aims at characterizing global gene
      expression of Azospirillum lipoferum 4B following a 7-day-old interaction with
      two cultivars of Oryza sativa L. japonica (cv. Cigalon from which it was
      originally isolated, and cv. Nipponbare). The analysis was done on a whole genome
      expression array with RNA samples obtained from planktonic cells, sessile cells,
      and root-adhering cells. Root-associated Azospirillum cells grow in an active
      sessile-like state and gene expression is tightly adjusted to the host plant.
      Adaptation to rice seems to involve genes related to reactive oxygen species
      (ROS) detoxification and multidrug efflux, as well as complex regulatory
      networks. As revealed by the induction of genes encoding transposases,
      interaction with root may drive bacterial genome rearrangements. Several genes
      related to ABC transporters and ROS detoxification display cultivar-specific
      expression profiles, suggesting host specific adaptation and raising the question
      of A. lipoferum 4B/rice cv. Cigalon co-adaptation. 

PMID- 24283407
TI  - Self-assembly of left- and right-handed molecular screws.
AB  - Stereoselectivity is a hallmark of biomolecular processes from catalysis to self
      assembly, which predominantly occur between homochiral species. However, both
      homochiral and heterochiral complexes of synthetic polypeptides have been
      observed where stereoselectivity hinges on details of intermolecular
      interactions. This raises the question whether general rules governing
      stereoselectivity exist. A geometric ridges-in-grooves model of interacting
      helices indicates that heterochiral associations should generally be favored in
      this class of structures. We tested this principle using a simplified molecular
      screw, a collagen peptide triple-helix composed of either l- or d-proline with a
      cyclic aliphatic side chain. Calculated stabilities of like- and opposite-handed
      triple-helical pairings indicated a preference for heterospecific associations.
      Mixing left- and right-handed helices drastically lowered solubility, resulting
      in micrometer-scale sheet-like assemblies that were one peptide-length thick as
      characterized with atomic force microscopy. X-ray scattering measurements of
      interhelical spacing in these sheets support a tight ridges-in-grooves packing of
      left- and right-handed triple helices. 

PMID- 24283408
TI  - Life-threatening course of pemphigus vulgaris complicated by sepsis caused by
      azathioprine-induced bone marrow suppression, successfully managed with
      combination therapy.
AB  - Severe forms of pemphigus vulgaris (PV) that are resistant to standard treatment
      present a life-threatening disease with a mortality of 5-10%. The treatment is
      usually individualized. The most popular procedures used today include
      intravenous applications of immunoglobulins and rituximab. Currently the common
      use of pulse corticosteroids, often in first-line treatment, is being neglected.
      This particular case documented the severity of the disease and also the need for
      combined and comprehensive care, in which corticosteroid pulse therapy still
      plays an important role. 

PMID- 24283409
TI  - Clinical relevance is associated with allergen-specific wheal size in skin prick
      testing.
AB  - BACKGROUND: Within a large prospective study, the Global Asthma and Allergy
      European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout
      Europe to make recommendations for SPT in clinical settings. OBJECTIVE: To
      improve clinical interpretation of SPT results for inhalant allergens by
      providing quantitative decision points. METHODS: The GA(2) LEN SPT study with
      3068 valid data sets was used to investigate the relationship between SPT results
      and patient-reported clinical relevance for each of the 18 inhalant allergens as
      well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic
      dermatitis, food allergy). The effects of age, gender, and geographical area on
      SPT results were assessed. For each allergen, the wheal size in mm with an 80%
      positive predictive value (PPV) for being clinically relevant was calculated.
      RESULTS: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites)
      of the positive SPT reactions (wheal size >= 3 mm) were associated with patient
      reported clinical symptoms when exposed to the respective allergen. The risk of
      allergic symptoms increased significantly with larger wheal sizes for 17 of the
      18 allergens tested. Children with positive SPT reactions had a smaller risk of
      sensitizations being clinically relevant compared with adults. The 80% PPV varied
      from 3 to 10 mm depending on the allergen. CONCLUSION: These 'reading keys' for
      18 inhalant allergens can help interpret SPT results with respect to their
      clinical significance. A SPT form with the standard allergens including mm
      decision points for each allergen is offered for clinical use.

PMID- 24283410
TI  - Testosterone 2% gel can normalize testosterone concentrations in men with low
      testosterone regardless of body mass index.
AB  - INTRODUCTION: Little is known about the effect of body mass index (BMI) on the
      efficacy and safety of testosterone therapy in hypogonadal men. A prior
      noncomparative trial demonstrated that testosterone 2% gel restored testosterone
      levels in hypogonadal men and was generally well tolerated. AIM: This post hoc
      analysis evaluated the influence of BMI on the pharmacokinetics of testosterone
      therapy in men with low testosterone. METHODS: Men (N = 149) aged 18-75 applied
      testosterone 2% gel to the front and inner thigh once daily for 90 days. Starting
      dose was 40 mg/day, which could be adjusted at days 14, 35, and 60. Patients were
      split into categories depending on baseline BMI: Tertile 1 (<= 29.1 kg/m(2)),
      Tertile 2 (29.2-32.4 kg/m(2)), and Tertile 3 (>32.4 kg/m(2)). MAIN OUTCOME
      MEASURES: Efficacy end points were average serum total testosterone
      concentrations over 24 hours and maximum serum testosterone concentrations at day
      90. Adverse events were recorded. RESULTS: The efficacy analysis included 129 men
      with low testosterone (mean age 52.9, 54.0, and 54.2 years for Tertiles 1, 2, and
      3, respectively) defined as serum testosterone <250-300 ng/dL. Baseline
      testosterone levels were comparable across BMI tertiles. After 90 days of
      treatment with testosterone 2% gel (>= 40 mg/day), 79.1%, 79.5%, and 73.8% of
      patients in Tertiles 1, 2, and 3, respectively, achieved serum testosterone
      concentrations in the physiologic range (i.e., >= 300 to <= 1,140 ng/dL). The
      mean average daily dose at day 90 was higher in participants in Tertiles 3 vs. 2
      (P = 0.039) and Tertiles 3 vs. 1 (P = 0.010). The gel was generally well
      tolerated, with skin reactions the most commonly reported adverse event (16.1%; n
      = 24). CONCLUSIONS: In this study, daily application of testosterone 2% gel was
      effective at returning serum testosterone to physiologic levels in men with low
      testosterone and high BMI, although required dose was affected by BMI.

PMID- 24283411
TI  - The dependence of graphene Raman D-band on carrier density.
AB  - Raman spectroscopy has been an integral part of graphene research and can provide
      information about graphene structure, electronic characteristics, and electron
      phonon interactions. In this study, the characteristics of the graphene Raman D
      band, which vary with carrier density, are studied in detail, including the
      frequency, full width half-maximum, and intensity. We find the Raman D-band
      frequency increases for hole doping and decreases for electron doping. The Raman
      D-band intensity increases when the Fermi level approaches half of the excitation
      energy and is higher in the case of electron doping than that of hole doping.
      These variations can be explained by electron-phonon interaction theory and
      quantum interference between different Raman pathways in graphene. The intensity
      ratio of Raman D- and G-band, which is important for defects characterization in
      graphene, shows a strong dependence on carrier density. 

PMID- 24283413
TI  - Genetic score of power-speed and endurance track and field athletes.
AB  - Athletic excelling capability in a specific sport results from the combined
      influence of hundreds of genetic polymorphisms. The aim of the current study was
      to characterize athletes' polygenetic scores. We developed two polygenetic
      scores: (a) Power Genetic Distance Score based on two polymorphisms (PGDS2;
      ACE(I/D), ACTN3(C/T)) or five polymorphisms (PGDS5; ACTN3(C/T), ACE(I/D), IL6(
      174G/C), NOS3(T/C), AGT(MET235THR)); and (b) Endurance Genetic Distance Score
      based on two polymorphisms (EGDS2; ACEI / D , ACTN3C / T ) or five polymorphisms
      (EGDS5; PPARGC1(AGly482Ser), PPAR(Aintron7G/C), PPARD(T294C), NRF2(A/C),
      HIF(C/T)). Eighty-two power-speed athletes, 87 endurance athletes, and 119
      nonathletic controls participated in the study. Genomic DNA was extracted from
      peripheral blood. Power-speed athletes' mean PGDS2 (46.1) and PGDS5 (29.4) were
      significantly higher compared with their mean EGDS2 (36.4) and EGDS5 (23.1; P <
      0.05, P < 0.01, respectively); and compared with controls' mean PGDS2 (36.6) and
      PGDS5 (24.2; P < 0.05, P < 0.05, respectively). Endurance athletes' mean EGDS2
      (60.3) and EGDS5 (35.3) were significantly higher compared with their mean PGDS2
      (26.9) and PGDS5 (21.8; P < 0.001, P < 0.001, respectively); and compared with
      controls' mean EGDS2 (51.2) and EGDS5 (26.1; P < 0.05, P < 0.001, respectively).
      We conclude that polygenetic scores can differentiate power-speed from endurance
      athletes. Whether these scores may be used to identify elite power-speed or
      endurance athletes' needs to be addressed in future studies.

PMID- 24283412
TI  - Encapsulation of DNA in macroscopic and nanosized calcium alginate gel particles.
AB  - Calcium alginate beads, which are biodegradable and biocompatible, have been
      widely employed as delivery matrices for biomacromolecules. In the present work,
      the feasibility of encapsulation of DNA (which is used as a model
      biomacromolecule) in calcium alginate nanobeads (sub-200 nm size), prepared using
      a recently developed protocol based on the phase inversion temperature (PIT)
      emulsification method [Machado et al. Langmuir 2012, 28, 4131-4141], was
      assessed. The properties of the nanobeads were compared to those of the
      corresponding macroscopic (millimeter sized) calcium alginate beads. It was found
      that DNA, representing a relatively stiff and highly charged polyanion (thus like
      charged to alginate), could be efficiently encapsulated in both nanosized and
      macroscopic beads, with encapsulation yields in the range of 77-99%. Complete
      release of DNA from the beads could be accomplished on dissolution of the gel by
      addition of a calcium-chelating agent. Importantly, the DNA was not denatured or
      fragmented during the preparation and collection of the nanobeads, which are good
      indicators of the mildness of the preparation protocol used. The calcium alginate
      nanobeads prepared by the herein utilized protocol thus show good potential to be
      used as carriers of sensitive biomacromolecules. 

PMID- 24283414
TI  - Polymer-mediated formation and assembly of silver nanoparticles on silica
      nanospheres for sensitive surface-enhanced Raman scattering detection.
AB  - To impart a desired optical property to metal nanoparticles (NPs) suitable for
      surface-enhanced Raman scattering (SERS) applications, it is crucial to assemble
      them in two or three dimensions in addition to controlling their size and shape.
      Herein, we report a new strategy for the synthesis and direct assembly of Ag NPs
      on silica nanospheres (AgNPs-SiNS) in the presence of poly(ethylene glycol) (PEG)
      derivatives such as PEG-OH, bis(amino)-PEGs (DA-PEGs), and O,O'-bis(2
      aminopropyl)PEG (DAP-PEG). They exhibited different effects on the formation of
      Ag NPs with variable sizes (10-40 nm) and density on the silica surface. As the
      molecular weight (MW) of DA-PEGs increased, the number of Ag NPs on the silica
      surface increased. In addition, DAP-PEG (MW of 2000), which has a 2-aminopropyl
      moiety at both ends, promoted the most effective formation and assembly of
      uniform-sized Ag NPs on a silica surface, as compared to the other PEG
      derivatives with the same molecular weight. Finally, we demonstrated that AgNPs
      SiNS bearing 4-fluorobenzenethiol on its surface induced the strong SERS signal
      at the single-particle level, indicating that each hybrid particle has internal
      hot spots. This shows the potential of AgNPs-SiNS for SERS-based sensitive
      detection of target molecules. 

PMID- 24283415
TI  - TB or not TB?

PMID- 24283416
TI  - Homocysteine in dogs with systemic inflammatory response syndrome.
AB  - OBJECTIVES: To compare serum concentrations of homocysteine in healthy dogs and
      those fitting the criteria for systemic inflammatory response syndrome and to
      compare these values to commonly measured B-vitamins. METHODS: Study dogs were
      classified into non-infectious systemic inflammatory response syndrome or sepsis
      groups and blood was drawn on Day 1 of the patient's hospitalisation for
      measurement of serum homocysteine, folate and cobalamin concentrations.
      Homocysteine concentration was measured in 51 clinically healthy dogs to serve as
      the control group. RESULTS: A statistically significant difference was found
      between the homocysteine concentrations of the healthy group when compared to non
      infectious systemic inflammatory response syndrome and sepsis groups.
      Homocysteine values were not correlated with folate, cobalamin or APPLEfast
      severity scores. Homocysteine concentrations were significantly lower in sick
      dogs when compared to the control group, which is dissimilar to the human
      population. CLINICAL SIGNIFICANCE: The clinical significance of homocysteine
      changes in critically ill dogs is currently unknown.

PMID- 24283417
TI  - Septic peritonitis from pyloric and non-pyloric gastrointestinal perforation:
      prognostic factors in 44 dogs and 11 cats.
AB  - OBJECTIVES: To identify potential prognostic factors affecting outcome in septic
      peritonitis caused by gastrointestinal perforation in dogs and cats. METHODS: A
      retrospective study. Animals operated on for septic peritonitis because of
      gastrointestinal perforation were evaluated. Risk factors assessed included age,
      duration of clinical signs, recent prior abdominal surgery, recent prior anti
      inflammatory drug administration, placement of a closed-suction drain and
      location of perforation. RESULTS: Fifty-five animals (44 dogs and 11 cats) were
      included. The overall mortality was 63.6%. No association was found between age,
      duration of clinical signs or prior abdominal surgery and outcome. Animals with a
      history of prior anti-inflammatory drugs were significantly (P=0.0011) more
      likely to have perforation of the pylorus (73.3%). No significant difference in
      outcome was found between animals treated with closed-suction drains and those
      treated with primary closure or between pyloric perforation and perforation at
      other gastrointestinal sites. CLINICAL SIGNIFICANCE: Administration of anti
      inflammatory drugs in dogs and cats is a significant risk factor for pyloric
      perforation. Pyloric perforation was not associated with a poorer outcome than
      perforation at other gastrointestinal sites. Placement of a closed suction drain
      did not improve outcome compared to primary closure.

PMID- 24283418
TI  - Differentiating between feline pleural effusions of cardiac and non-cardiac
      origin using pleural fluid NT-proBNP concentrations.
AB  - OBJECTIVE: To assess whether pleural fluid and urine amino terminal proB-type
      natriuretic peptide (NT-proBNP) can distinguish cardiac from non-cardiac causes
      of pleural effusion. METHODS: Blood, urine and pleural fluid were prospectively
      collected from cats presenting with pleural effusion categorised as cardiac or
      non-cardiac in origin. NT-ProBNP concentrations were measured using a feline
      specific enzyme-linked immunosorbent assay. Groups were statistically compared
      and receiver operating characteristic curves constructed to determine cut-offs to
      distinguish cardiac from non-cardiac pleural effusion in plasma, pleural fluid
      and urine. RESULTS: Forty cats with pleural effusion (22 cardiac and 18 non
      cardiac) were studied. NT-proBNP concentrations in plasma and pleural fluid were
      strongly correlated. Plasma (P<0.001) and pleural fluid (P<0.001) NT-proBNP
      concentrations and urinary NT-proBNT/creatinine ratios (P=0.035) were
      significantly higher in the cardiac group. After receiver operating
      characteristic curve analysis a plasma NT-proBNP cut-off of 214.3 pmol/mL was
      suggested [sensitivity=86.4% (95% CI: 66.7 to 95.3%), specificity=88.9% (95% CI:
      67.2 to 96.9%)] and a pleural fluid NT-proBNP cut-off of 322.3 pmol/mL was
      suggested [sensitivity=100% (95% CI: 85.1 to 100%), specificity=94.4% (95% CI:
      74.2 to 99.0%)]. No cut-off with adequate sensitivity and specificity for urinary
      NT-proBNP/creatinine ratios was suggested. CLINICAL SIGNIFICANCE: Measurement of
      NT-proBNP in pleural fluid distinguishes cardiac from non-cardiac causes of
      pleural effusion in cats.

PMID- 24283419
TI  - Comparative study of longevity, growth, and biomarkers of metal detoxication and
      oxidative stress between normal and deformed Aphanius fasciatus (Pisces,
      Cyprinodontidae).
AB  - This study compared fish longevity, growth, and oxidative stress between normal
      and deformed Aphanius fasciatus collected from the Gulf of Gabes. For this
      purpose, fish were collected from control (S1) and polluted (S2) sites in
      Tunisian coast and percentages of spinal deformities were determined. Oxidative
      stress biomarkers were also compared between normal and deformed fish, including
      levels of protein sulfhydryl (SH), malondialdehyde (MDA), and metallothioneins
      (MT), as well as activities of superoxide dismutase (SOD) and alkaline
      phosphatase (AP). Levels of heavy metals (Cd, Cu, and Zn) and polycyclic aromatic
      hydrocarbons (PAH) were also measured. Data showed that the highest occurrence of
      deformities was observed in younger fish and decreased significantly thereafter
      with age. Chemical analysis demonstrated high levels of heavy metals and PAH at
      polluted sites compared to a reference location. In deformed fish, a growth
      perturbation marked by a decrease of growth rate and condition index (CI), a high
      accumulation of Cd was noted. In addition, oxidative stress marked by changes in
      the studied biomarkers was observed. Taken together, oxidative stress, diminished
      longevity, and a disturbance of growth may be considered to be responsible
      factors contributing to spinal deformities. 

PMID- 24283420
TI  - Differential toxic responses between pristine and functionalized multiwall
      nanotubes involve induction of autophagy accumulation in murine lung.
AB  - Carbon nanotubes (CNT) are becoming commonly used in industrial applications.
      However, the toxicity associated with this material remains to be established.
      The aim of this study was to investigate the potential toxic mechanisms
      associated with multiwall carbon nanotubes (MWCNT) in normal mouse lung. A total
      of 100 MUg of two types of MWCNT, namely, pristine MWCNT (PMWCNT) and acid
      treated-MWCNT (TMWCNT), was administered to male C57BL/6 mice via intratracheal
      (IT) instillation for a period of 6 mo. Our results indicated that PMWCNT induced
      pulmonary autophagy accumulation and resulted in more potent tumorigenic effects
      compared to TMWCNT. Accordingly, MWCNT may exert differential toxicity attributed
      to various physicochemical properties. Data emphasize the need for careful
      regulation of production and use of CNT. 

PMID- 24283421
TI  - Black-currant protection against oxidative stress formation.
AB  - The aim of this study was to investigate the influence of black-currant juice on
      chronic ethanol-induced oxidative stress and its consequences in liver, brain,
      and serum of rats. Data demonstrated that administration of black-currant juice
      to rats improved antioxidant abilities in the examined tissues as evidenced by
      measurement of activities of Cu,Zn-superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R), as well as
      levels of glutathione (GSH) and vitamins C, E, and A. Ethanol intoxication
      produced a decrease in the activities and levels of the antioxidants just listed,
      and the decrease was accompanied by a reduction in levels of arachidonic acid
      (AA) and docosahexaenoic acid (DHA). Further results showed enhanced lipid
      peroxidation as determined by malondialdehyde (MDA), 4-hydroxynonenal (4-HNE),
      and neuroprostanes and elevated protein levels such as carbonyl groups and
      dityrosine. Ethanol intoxication altered liver metabolism as evidenced by a
      decrease in peroxisome proliferator-activated-receptor (PPARalpha), AMP-dependent
      protein kinase (AMPK), and nuclear factor kappa B cells (NFkappaB) and by an
      increase in tumor necrosis factor (TNF-alpha) expression. Administration of black
      currant juice to ethanol-intoxicated rats exerted an antioxidant response by
      restoring to normal quantities the antioxidant levels and enzyme activities and
      prevented lipid and protein oxidative effects. The activities of alanine
      transaminase and aspartate transaminase, biomarkers of liver damage, returned to
      normal after black-currant treatment of ethanol-administered animals. In
      addition, the expression of PPARalpha, AMPK, TNF-alpha, and NFkappaB confirmed
      the protective effect of the juice. Data thus indicate the extensive antioxidant
      metabolic effects of black-currant juice that may be beneficial for humans. 

PMID- 24283422
TI  - Protective effect of chlorophyllin and lycopene from water spinach extract on
      cytotoxicity and oxidative stress induced by heavy metals in human hepatoma
      cells.
AB  - The purpose of this study was to examine the inhibitory effects of ethanol
      extract of water spinach (EEWS) containing chlorophyll and lycopene on
      cytotoxicity and oxidative stress in liver induced by heavy metals. The (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay and
      dichlorofluorescein (DCF) assay were conducted to measure cytotoxicity and
      inhibition of reactive oxygen species (ROS), respectively. Cytotoxicity was
      prevented at a concentration of 11.7 mg/L of EEWS. Both sodium copper
      chlorophyllin (SCC) and lycopene in EEWS were identified by ultraperformance
      liquid chromatography-photodiode array-electrospray ionization-mass spectroscopy
      (UPLC-PDA-ESI-MS/MSn) as major components at m/z 722.64 and 535.45, respectively.
      The concentrations of SCC and lycopene were 0.12 and 0.04 mg from 100 g of dried
      powder, respectively. Approximately 99% cytotoxicity induced by Cd was inhibited
      by EEWS. However, the inhibitory effect attributed to generation of ROS was
      similar with SCC, lycopene, and EEWS. Our results indicated that EEWS was
      effective in reducing cytotoxicity and oxidative stress produced by heavy metals
      in a HepG2 cell. Data suggest that the possible mechanism underlying the
      preventive action of SCC might be associated with diminished absorption of metal
      ions by chelating and blocking metal-mediated generation of ROS, while lycopene
      effects may be attributed to its high number of conjugated dienes that act as
      most potent singlet oxygen quenchers. 

PMID- 24283424
TI  - Role of cytokines in multiple sclerosis and experimental autoimmune
      encephalomyelitis.

PMID- 24283423
TI  - "I have a good life": the meaning of well-being from the perspective of young
      adults with Down syndrome.
AB  - PURPOSE: The purposes of this study were to explore what makes for a "good life"
      from the perspective of young adults with Down syndrome and to identify the
      barriers and facilitators to participation. METHODS: Twelve young adults with
      Down syndrome participated in individual and group discussions. Each session
      began with individual discussions between a researcher and participant, allowing
      each individual to express their views in their own words. Following individual
      discussions, participants joined a larger group facilitated by the researchers
      which allowed for collective reflection and sharing of experiences. Individual
      discussions were recorded on large poster size pieces of paper through drawings
      and writing using colourful pens by the participants themselves or with
      assistance from researchers. Group discussions were audio recorded and one
      researcher recorded field notes on contextual information. Data were analyzed
      through open coding and constant comparison techniques to identify categories
      which were then collapsed into the main themes. RESULTS: Analysis of the
      transcripts revealed four main themes: "Relationships", "Community
      participation", "Independence" and "Hopes for the future". These findings
      highlighted the participants' desire for autonomy, particularly in the domains of
      living independently and employment. Family relationships and community services
      were described as both facilitators and barriers to their participation.
      CONCLUSION: Overall, the findings from this study revealed that the participants'
      life perspective was positive, with a general consensus of, "I have a good life".
      This study yielded many recommendations that could be integrated into transition
      models of service delivery for young adults with Down syndrome as they develop
      from adolescence into adulthood. IMPLICATIONS OF REHABILITATION: Young people
      with Down syndrome want to make decisions for themselves. Community participation
      is important for young adults with Down syndrome. Young people with Down syndrome
      have dreams and aspirations for their future, and should be fully engaged in
      planning for transition from school.

PMID- 24283425
TI  - Guillain-Barre syndrome with severe persistent disability: relationship to
      hyperacute Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is a heterogeneous condition with a variable
      prognosis. We studied nine patients who were unable to walk unaided 12 months
      after the onset of their illness to discover whether they belonged to a more
      homogeneous subgroup. Sis of the nine patients had symptoms of gastroenteritis
      shortly before the onset of their neuropathic symptoms and a hyperacute onset of
      weakness so that they were bed-bound within 24 h. These patients had
      predominantly motor rather than sensory involvement We compared these nine poor
      outcome patients with 66 patients with lesser degrees of persistent disability of
      whom only three had both a history of prodromal gastroenteritis and a hyperacute
      onset (p < 0.0001). The poor and better outcome groups did not differ
      significantly in the severity of disability or other clinical or
      neurophysiological features in the acute stage. Patients with previous
      gastroenteritis and hyperacute onset of weakness may represent a relatively
      homogeneous subgroup of "hyperacute GB" in which severe axonal damage is caused
      by an aberrant immune response to a gastrointestinal pathogen such as
      Campylobacter jejuni. 

PMID- 24283426
TI  - Outcome of intracerebral hemorrhage: clinical and CT findings in 326 patients.
AB  - Clinical symptoms and findings in cranial computed tomography (CT) were evaluated
      in 326 patients with intracerebral hemorrhage (ICH). Localizations of ICH were
      the lobes (n = 254), the basal ganglia (n = 46), the pons and brain stem (n = 13)
      and the cerebellum (n = 8). Multiple hematomas were present in nine patients. An
      initial coma (n = 225) was most frequent in ICH of the pons (n = 7), cerebellum
      (n = 6), and the frontal (n = 71) and temporal (n = 66) lobes. Epileptic seizures
      (n = 70) were most common in hematomas of the frontal (n = 24), temporal (n = 19)
      and parietal (n = 12) lobes and the basal ganglia (n = 6). A history of
      hypertension was given in 140 patients; 119 of these had an ICH with a size of
      >=3 cm. Mortality (n = 162) was high with ICH in the pons and brain stem (10 out
      of 13), in the frontal (54 out of 98) and parietal (32 out of 58) lobes and the
      basal ganglia (n = 23). A size of the ICH of 3 cm or more in cranial CT and an
      associated ventricular hemorrhage were associated with a bad outcome. An initial
      disturbance of consciousness was the only reliable clinical predictor of outcome
      (chi-square, p < 0.001). Katamnestic evaluation of 66 of the 164 survivors after
      5.2 years revealed seizures in 20 patients and mild neurological deficits in 41.
      Another 14 patients were partially, and nine totally dependent Nineteen patients
      had died in between; there was only one death attributable to another ICH. 

PMID- 24283427
TI  - Interictal "patchy" regional cerebral blood flow patterns in migraine patients. A
      single photon emission computerized tomographic study.
AB  - In 92 migraine patients and 44 healthy control subjects we recorded regional
      cerebral blood flow (rCBF) with single photon emission computerized tomography
      and (133) Xe inhalation or with i.v. (99m) Tc-HMPAO. Migraine patients were
      studied interictally. A quantitated analysis of right-left asymmetry indices in a
      fixed set of regions of interest was compared with the normal asymmetry indices
      in the healthy controls. An asymmetry index deviating more than +/- 2.5 S.D.s in
      normals was defined as pathological asymmetry. By quantitated analysis 47% of
      images from patients with aura attacks and 48% of images from patients without
      aura attacks were established to contain higher rate of asymmetries, the
      difference being statistically significant (p < 0.05, Wilcoxon). A blinded visual
      analysis and scoring by a four level scale were done by four experienced
      observers. rCBF images from 18% of patients having attacks with aura and from 19%
      of patients without aura attacks was scored as containing abnormal right-left
      asymmetries by the visual analysis. Images from healthy controls were all scored
      to be normal. In 37% of the images (all from patients) there was lack of
      consensus among observers (kappa = 0.28). There was no correlation between visual
      or quantitated abnormalities and age, duration of migraine, frequency of attacks
      or prophylactic medication. No correlation could be established between
      asymmetries and the usual side of headache or aura symptoms. Two conclusions
      emerged: (1) visual evaluation of interictal migraine rCBF images is insufficient
      to pick up abnormalities; (2) almost 50% of the migraine sufferers had abnormal
      rCBF/asymmetries. However, these are discrete compared with those typically seen
      during the aura phase of a migraine attack. One explanation to the patchy rCBF
      patterns might be that they reflect interictal cerebrovascular dysregulation
      which might to be a common feature in both types of migraine. 

PMID- 24283428
TI  - Clinical course and risk factors of neurotoxicity following cisplatin in an
      intensive dosing schedule.
AB  - An intensive weekly regimen of cisplatin was administered to 66 patients with
      solid cancer in doses varying from 70 to 85 mg/m(2) . The occurrence of sensory
      neuropathy was prospectively examined by assessment of neuropathic signs and
      symptoms and measurement of vibration perception threshold (VPT). Evaluation was
      performed before initiation of therapy and during follow-up until 3-12 months
      after the last cycle of cisplatin. A mild or moderate neuropathy developed in 47%
      of patients at 2 weeks after treatment This neuropathy continued to deteriorate
      until approximately 3 months after cessation of chemotherapy leading to a mild or
      moderate neuropathy in 71% of patients and a severe neuropathy in 9% of patients.
      Thereafter we observed a gradual but incomplete recovery. The high incidence of
      neuropathy we found may be explained by the prolonged observation period compared
      with earlier reports. The only factor correlated with severity of neuropathy was
      the cumulative dose of cisplatin, while there was no association with either pre
      treatment VPT, age, sex, tumor type or co-treatment with etoposide. The
      progressing course up to approximately 3 months after the end of treatment
      underscores the need for prolonged follow-up in future studies on cisplatin
      neuropathy.- 

PMID- 24283429
TI  - The Brown-Vialetto-van Laere syndrome: a case report and literature review.
AB  - We describe a female presenting with a progressive bulbar palsy, deafness and
      respiratory failure necessitating long-term ventilation. These clinical features
      are consistent with the Brown-Vialetto-van Laere syndrome, a rare, sometimes
      inherited progressive ponto-bulbar neuronopathy with associated deafness. This
      case provides further evidence of the genetic heterogeneity of the syndrome and
      we describe a previously unreported form of treatment which had negative results.
      We suggest that improved recognition of this rare syndrome is essential to
      provide aetiological clues and we describe the worthwhile symptomatic improvement
      which can be achieved with simple supportive measures. 

PMID- 24283430
TI  - Evaluation of gelatinases and IL-6 in the cerebrospinal fluid of patients with
      optic neuritis, multiple sclerosis and other inflammatory neurological diseases.
AB  - The activities of the metalloproteinase gelatinase B, and the presence of IL-6,
      an inducer of metalloproteinase inhibitors, were investigated in CSF samples of
      190 patients with multiple sclerosis (MS; n = 55), optic neuritis (ON; n = 46),
      other inflammatory neurological diseases (OIND; n = 27) or control patients (CON)
      with non-inflammatory neurological diseases (n = 62). IL-6, measurable as
      hybridoma growth factor activity (detection limit 3 pg/ml), was found in only
      four of these 190 CSF samples (three OIND, one CON). Elevated CSF gelatinase B
      levels were detected in 40%, 35% and 54% of the patients with MS, ON and OIND,
      respectively, while all control CSFs were devoid of gelatinase B activity.
      Clinical and laboratory data were compared with gelatinase B levels. No
      correlation was found between the CSF cytoses and gelatinase B levels, suggesting
      that this enzyme in the CSF originates from CNS lesions rather than from CSF
      cells. However, the occurrence of the gelatinase B significantly correlated with
      the IgG index in the MS patient group. This study stimulates further
      investigation into the possible usage of protease inhibition in demyelinating
      diseases. 

PMID- 24283431
TI  - The relevance of clinical subtypes for disease course, family history and
      epidemiological variables in Parkinson's disease.
AB  - Clinical outcome and relevance of genetic and epidemiological factors were
      evaluated in 161 patients with idiopathic Parkinson's disease (PD) with regard to
      onset symptoms [tremor (T) vs non-tremor (NT)], to clinical classification into
      tremor-dominant (TD), alkineto-rigid (AR), and equivalent (EQ) subtypes, and to
      disease onset before the 45th year of age (EO) and after age 69 (LO). Patients
      were investigated by questionnaire-based personal interview and clinical
      examination. Allegedly symptomatic first-degree relatives were examined
      personally or had sufficient medical documentation to allow neurological
      diagnosis. Disease course was more favorable in T than in NT, in TD than in AR or
      EQ, and in EO compared with LO. Among EO and LO patients, clinical subtypes TD,
      AR and EQ were not differently distributed. Frequency of first-degree relatives
      with PD or essential tremor and any epidemiological variable tested were not
      elicited differently between TD, AR and EQ patients, with the exception that TD
      reported more frequent premorbid travelling. EO patients reported higher
      frequencies of premorbid head trauma and rural living than LO patients. The more
      favorable disease prognosis of patients with predominant tremor at presentation
      and of patients with early disease onset is corroborated. Clinical subgroups do
      not differ in genetic and epidemiological factors. 

PMID- 24283432
TI  - A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks.
AB  - Supersensitivity to induction of headache and arterial dilatation by a donor of
      nitric oxide (nitroglycerin) has recently been demonstrated in migraine
      sufferers. The aims of the present study were to examine whether the nitric oxide
      donor nitroglycerin may induce a typical migraine attack, to exclude placebo
      related effects and to describe the relation between middle cerebral artery
      dilatation and provoked migraine. Nitroglycerin (0.5 MUg/kg/min for 20 min) or
      placebo was infused into 12 migraine patients in a double-blind cross-over trial.
      Blood velocity in the middle cerebral artery was measured with transcranial
      Doppler and characteristics of headache and accompanying symptoms were recorded
      frequently. Headache occurred during the nitroglycerin infusion as previously
      described but peak headache intensity did first occur 5.5 h after infusion. At
      this time the induced headaches in 8 of 10 completing patients fulfilled the
      diagnostic criteria for migraine without aura of the International Headache
      Society. Furthermore, all patients who normally had unilateral spontaneous
      migraine attacks also had unilateral headaches after nitroglycerin. Only one
      subject developed migraine after placebo (p < 0.03). The time pattern of headache
      and estimated middle cerebral artery dilatation corresponded well. The study
      therefore demonstrates that activation of the nitric oxide cGMP pathway may cause
      typical migraine attacks. 

PMID- 24283433
TI  - Cognitive profiles and regional cerebral blood flow patterns in dementia of the
      Alzheimer type.
AB  - Individual cognitive profiles and correlations between cognitive functions and
      regional cerebral blood flow (rCBF) were analyzed in 20 consecutive patients with
      a clinical diagnosis of probable Alzheimer's disease (AD). CBF was measured with
      high resolution single photon emission computed tomography (SPECT) and [(99m)
      Tc]d,l-HMPAO. The analysis of cognitive profiles was based on the composite
      scores for six cognitive domains, derived from a detailed neuropsychological test
      battery, as compared with corresponding test data obtained in a control group of
      28 age-matched healthy volunteers. The cognitive profiles displayed a marked
      heterogeneity as concerned the general level of cognitive impairment, the number
      of significantly affected cognitive domains, the spectrum of affected and non
      affected cognitive domains, and the severity of each cognitive dysfunction.
      Statistically significant correlations with rCBF were found for memory scores
      (right frontal and temporal cortex), abstraction scores (frontal/parietal ratio
      of rCBF), language scores (left frontal and temporal cortex), visual perception
      scores (rCBF throughout the right hemisphere), and for visuo-construction scores
      (side-to-side asymmetry of parietal rCBF). We conclude that the previously
      observed topographical heterogeneity of rCBF distribution patterns in probable AD
      was reflected by differences in cognitive profiles. The observed heterogeneities
      stress the relevance of analyzing individual cognitive and rCBF data, as a
      supplement to group comparisons of data, in the investigation of diseases with
      potential heterogeneous affections of the brain. 

PMID- 24283434
TI  - Isolated palsy of the third nerve nuclear complex caused by cerebral
      toxoplasmosis.
AB  - We present a patient with palsy of the third nerve nuclear complex secondary to
      cerebral toxoplasmosis. There was a unique lesion by magnetic resonance and there
      were no other neurological symptoms. A complete radiographic and clinical
      resolution was obtained by specific treatment. Such neurological symptoms in
      cases of toxoplasmosis have not been reported previously. 

PMID- 24283435
TI  - Vertical saccade palsy: a presenting sign of Niemann-Pick type IIS.
AB  - An 8 year old sister of a patient undergoing investigations for Niemann-Pick type
      IIS was observed to have mild difficulties in making downward saccades. She had
      no other symptoms apart from longstanding mild learning difficulties. Detailed
      eye movement assessment, using horizontal and vertical electro-oculography and
      video monitoring, revealed normal horizontal but abnormal vertical eye movements.
      Vertical downward saccades were absent and could only be achieved by mobilizing
      the bead to allow for headthrusts. Upward saccades were present at initial
      presentation, however a subsequent recording after 10 months revealed an
      inability to make upward saccades unless accompanied by blinks. Vertical
      optokinetic nystagmus was absent, although vertical smooth pursuit and vestibular
      ocular reflex were present. Cultured skin fibroblasts showed defective
      cholesterol esterification which confirmed the diagnosis of Niemann-Pick type IIS
      (previously known as type C). Vertical saccade palsy has been described as part
      of the neurological deficits, however it has not been previously reported as the
      presenting sign of Niemann-Pick type IIS. 

PMID- 24283436
TI  - Chronic paraparesis associated with human T-lymphotropic virus type I beginning
      after dental extraction.
AB  - We report a patient with a chronic paraparesis associated with human T
      lymphotropic virus I infection (HTLV-I antibodies were present in blood and CSF),
      which began after a dental extraction. We suggest the possible relation of the
      dental procedure with the triggering of the disease. 

PMID- 24283437
TI  - Quantitative structure and bioactivity relationship study on HCV NS5B polymerase
      inhibitors.
AB  - Several QSAR (quantitative structure-activity relationship) models for predicting
      the inhibitory activity of 333 hepatitis C virus (HCV) NS5B polymerase inhibitors
      were developed. All the inhibitors are HCV polymerase non-nucleoside analogue
      inhibitors (NNIs) fitting into the pocket of the NNI III binding site. For each
      molecule, global descriptors and 2D property autocorrelation descriptors were
      calculated from the program ADRIANA.Code. Pearson correlation analysis was used
      to select the significant descriptors for building models. The whole dataset was
      split into a training set and a test set randomly or using a Kohonen's self
      organizing map (SOM). Then, the inhibitory activity of 333 HCV NS5B polymerase
      inhibitors was predicted using multilinear regression (MLR) analysis and support
      vector machine (SVM) method, respectively. For the test set of the best model
      (Model 2B), correlation coefficient of 0.91 was achieved. Some molecular
      descriptors, such as molecular complexity (Complexity), the number of hydrogen
      bonding donors (HDon) and the solubility of the molecule in water (log S) were
      found to be very important factors which determined the bioactivity of the HCV
      NS5B inhibitors. Some other molecular properties such as electrostatic and charge
      properties also played important roles in the interaction between the ligand and
      the protein. The selected molecular descriptors were further confirmed by
      analysing the interaction between two representative inhibitors and the
      polymerase in their crystal structures. 

PMID- 24283438
TI  - Cervical cerclage and type of suture material: a survey of UK consultants'
      practice.
AB  - OBJECTIVE: The main aim of the survey was to explore current practices with
      regards to cervical cerclage procedures amongst UK consultants with particular
      emphasis on the type of suture material used. METHODS: An electronic survey of UK
      consultant members and fellows of the Royal College of Obstetricians and
      Gynaecologists and who previously agreed to be contacted for survey purposes.
      RESULTS: There were 261 respondents to the survey and 88% routinely performed
      cerclage. The majority performed the procedure between 12 and 16 weeks' gestation
      (88.7%; n = 180/203), following the McDonald technique (83.4%; n = 166/199) and
      using a braided suture material (86.6%; n = 175/202). Although only 27 of the 202
      responders (13.4%) used a monofilament suture for cerclage (75%; n = 149/201) of
      clinicians stated that they were not sure what is the best suture material to be
      used. CONCLUSION: There is considerable variation in practice amongst Consultant
      obstetricians with regards to cervical cerclage. Although most respondents use
      the traditional braided suture material, a significant proportion of them were
      not sure what is the best suture material to use. The "gestation at delivery"
      rate was judged to be the most important outcome for a future study.

PMID- 24283439
TI  - Cutaneous manifestations in Costello and cardiofaciocutaneous syndrome: report of
      18 cases and literature review.
AB  - Costello syndrome (CS) and cardiofaciocutaneous syndrome (CFCS) are congenital
      disorders involving the Ras-MAPK pathway with phenotypic overlap. These two
      entities are thought to share common cutaneous findings, although so far they
      have been poorly studied. The objective of this prospective observational study
      was to describe the spectrum of skin findings in CS and CFCS and to highlight
      those specific to each of these two diseases. Patients with a confirmed diagnosis
      of CFCS or CS underwent a systematic skin examination during the annual workshop
      organized by the French CS association in 2007 and 2009 in Bordeaux, France.
      Eighteen patients were included in the study. Specific skin abnormalities,
      including cutis laxa, curly hair, pruritus, and hyperhidrosis, are shared by CFCS
      and CS, whereas others may help to differentiate between these two syndromes.
      Acanthosis nigricans, papillomas, and loose thick skin of the dorsum of the hands
      are characteristic of CS, whereas sparse eyebrows and dry hyperkeratotic skin are
      suggestive of CFCS. Our results highlight that a systematic cutaneous
      examination, in addition to dysmorphologic and noncutaneous anomalies, may be
      helpful in establishing the diagnosis of CFCS and CS. The physiopathologic link
      between constitutional Ras-MAPK pathway activation and the observed ectodermal
      findings remains to be investigated. 

PMID- 24283440
TI  - Human papillomavirus (HPV) genotyping of cutaneous warts in Greek children.
AB  - The human papillomavirus (HPV) infects the squamous epithelium of the skin and
      produces common warts, plantar warts, and flat warts, which occur commonly on the
      hands, face, and feet. The objective of this study was to determine the presence
      of HPV in warts in children in order to associate the virus with the disease.
      Sixty-eight children with clinically diagnosed cutaneous warts were recruited.
      Skin biopsy samples were examined and DNA was extracted using a commercially
      available kit. To distinguish between the HPV types, we used a specific pair of
      primers to amplify the HPV DNA. Polymerase chain reaction amplification of the L1
      region was followed by restriction fragment length polymorphism analysis and
      Luminex xMAP technology. HPV 57 was the predominant type in our study, although
      the detection of the high-risk HPV type 16 in 33% of our positive samples
      indicates the presence of mucosal high-risk HPV types in the skin of children. It
      seems that the newly introduced Luminex assay maximized the discrimination of
      genotypes even in the case of multiple HPV infections. Or findings also suggest
      the presence of high-risk HPV types in cutaneous warts. 

PMID- 24283441
TI  - Skin ulcers and bone pain in a healthy 6-year-old female.

PMID- 24283442
TI  - Palmoplantar keratoderma in a 7-year-old boy.

PMID- 24283443
TI  - A red, white, and blue plaque on the flank of a newborn.

PMID- 24283444
TI  - Erythema multiforme after rabies vaccination.

PMID- 24283445
TI  - What is "psychodynamic psychiatry"?

PMID- 24283446
TI  - Using the internet to provide psychodynamic psychotherapy.
AB  - Over the last 15 years, there has been a substantial increase in research and
      clinical implementations of Internet-delivered, cognitive behavioral therapy
      (ICBT). Several studies on ICBT have been in the format of guided self-help where
      a therapist guides the patient throughout the whole treatment. ICBT is typically
      in the form of self-help material (e.g., text or video) which is provided to a
      client over the Internet with additional therapist contact by e-mail. ICBT has
      been shown to be effective for various conditions and, in some studies, has shown
      to be as effective as face-to-face cognitive behavioral therapy for mild to
      moderate depression, anxiety disorders, and somatic problems. Recently, the field
      has expanded to include other orientations including psychodynamic psychotherapy.
      Currently, there are three randomized controlled trials that have tested the
      efficacy of psychodynamic psychotherapy delivered in this format. The latest
      published trial focused on an affect-focused, psychodynamic psychotherapy
      delivered to a sample of participants with mixed depression and anxiety
      disorders. This article aims to provide a deeper understanding of the process of
      providing psychodynamic psychotherapy via the Internet. We will give a detailed
      description of our latest manual and show how psychotherapeutic work is conducted
      utilizing this text. Furthermore, we provide examples of dialogue between
      therapist and client from the online environment. Similarities and differences
      between psychodynamic psychotherapy delivered over the Internet and in face-to
      face formats are discussed.

PMID- 24283447
TI  - The psychodynamic psychotherapist's guide to the interaction among sex, genes,
      and environmental adversity in the etiology of depression for women.
AB  - From menarche to menopause, women are highly vulnerable to major depression.
      While biological and psychosocial differences between men and women have been
      established, the reason for the preponderance of depression in women has yet to
      be fully elucidated. Women may be predisposed to depressive illness because of
      biological factors related to brain structure, function, and the impact of
      reproductive life stages. They may also be at increased risk because they are
      differentially disadvantaged with respect to environmental stressors including
      interpersonal violence, socioeconomic instability, and caregiving burden, among
      others. However, not all women develop depression, nor do all individuals who
      suffer from adverse life events. This narrative review focuses on emerging
      research related to the interaction between sex, genetics, and environmental
      factors that may help offer clues about why some individuals suffer from
      depression, and why others may be resilient to this outcome. While many questions
      remain unanswered, the psychodynamic psychotherapist can use this information to
      help patients suffering from depression understand some of the complexities of
      the determinants of risk and resilience, with the goal of moving forward toward
      recovery.

PMID- 24283449
TI  - Managing borderline personality disorder on general psychiatric units.
AB  - Patients with Borderline Personality Disorder (BPD) are at high risk of suicide
      and are frequently hospitalized in the acute setting of emotional crisis, non
      suicidal self-injury, and suicidal behaviors. Historically, patients with BPD
      have borne tremendous stigma and have tended to overwhelm providers and care
      systems. The reconceptualization of the pathophysiology and development of BPD in
      the context of a rapidly changing health care environment warrants examination of
      relevant psychotherapeutic and treatment principles. Through a case discussion,
      this article highlights several factors relevant to acute inpatient
      hospitalization of patients with BPD in an academic training environment in an
      effort to identify both the challenges and helpful treatment philosophies and
      practices to advance patient care and promote recovery.

PMID- 24283450
TI  - Transfer of care of psychotherapy patients: implications for psychiatry training.
AB  - Transfers of care occur routinely in medical training, but the transfer of
      psychotherapy patients has received relatively little attention. This article
      discusses important issues concerning these transfers, using case examples and
      findings from a survey of the experience of psychiatry residents transitioning
      psychotherapy patients. Residents have difficulty telling patients they are
      leaving and often delay doing so. Because feelings of closeness and attachment
      can develop in long-term therapeutic relationships, residents describe feeling
      guilty, uncertain, anxious, sad, and occasionally relieved as they prepare their
      patients for transfer. Outgoing residents can feel anxious when recognizing and
      addressing their patients' and their own positive feelings. Incoming residents
      experience discomfort at being compared to the previous therapist and often
      encounter the patient's negative feelings at the transfer and the loss of the
      previous therapy. Teaching about the two poles of transfer of care is recommended
      to better understand and respond to this transition for both patient and
      therapist. This should include addressing the stresses involved and
      recommendations for management.

PMID- 24283451
TI  - Defense style as a predictor of change in interpersonal problems among patients
      attending day treatment for personality disorder.
AB  - BACKGROUND: Healthy interpersonal functioning, and a reduction of the distress
      associated with maladaptive interpersonal behavior, is a focus of treatment for
      personality disorder (PD). Patients with PD are also known to make a preferential
      use of immature defenses. We examined change in interpersonal problems as a
      critical outcome, and defense style as a predictor of this outcome. METHODS:
      Consecutively admitted patients to a group-oriented day treatment (DT) program
      were recruited (N = 32). Predictor variables were represented by subscale scores
      from the 40-item Defense Style Questionnaire (DSQ-40); outcomes were represented
      by the global distress and interpersonal octant scores from the 64-item Inventory
      of Interpersonal Problems-Circumplex (IIP-C). RESULTS: Significant inverse
      correlations were observed between Neurotic defenses and change in both
      interpersonal distress and problems associated with the Vindictive, Cold,
      Socially Inhibited, and Non-Assertive octants. Partial correlations, adjusting
      for baseline IIP-C scores, remained significant. Additional inverse relations
      between Neurotic defenses and improvement in the Domineering, Exploitable, and
      Overly Nurturant octants also emerged in the partial correlation analysis.
      DISCUSSION: Neurotic defenses are oriented to "splitting off" the affective
      element of experience; in the case of patients with PD, this affective element
      may often involve hostility. An orientation to use of Neurotic defenses also
      appears to be more trait-like and thus resistant to change. The findings
      highlight developing skill in affective communication, and addressing maladaptive
      interpersonal behaviors in the here-and-now, as mechanisms of therapeutic change
      in DT of patients with PD. LIMITATIONS: The sample was small and assessment of
      defense style and interpersonal problems relied on patient self-report.

PMID- 24283452
TI  - Psychodynamic-interpersonal therapy: an overview of the treatment approach and
      evidence base.
AB  - This article describes the development of Psychodynamic-Interpersonal Therapy or
      the Conversational Model of therapy, as it is also known. It includes a brief
      description of the approach to therapy, a review of the evidence base, and a
      brief description of qualitative and psychotherapy process research that has been
      conducted on the model.

PMID- 24283455
TI  - Surface Damage on Dental Implants with Release of Loose Particles after Insertion
      into Bone.
AB  - BACKGROUND: Modern dental implants present surface features of distinct
      dimensions that can be damaged during the insertion procedure into bone. PURPOSE:
      The aims of this study were (1) to quantify by means of roughness parameters the
      surface damage caused by the insertion procedure of dental implants and (2) to
      investigate the presence of loose particles at the interface. MATERIALS AND
      METHODS: Three groups of dental implants representing different surface
      topographies were inserted in fresh cow rib bone blocks. The surface roughness
      was characterized by interferometry on the same area before and after the
      insertion. Scanning electron microscopy (SEM)-back-scattered electron detector
      (BSD) analysis was used to identify loose particles at the interface. RESULTS:
      The amplitude and hybrid roughness parameters of all three groups were lower
      after insertion. The surface presenting predominance of peaks (Ssk [skewness] >
      0) associated to higher structures (height parameters) presented higher damage
      associated to more pronounced reduction of material volume. SEM-BSD images
      revealed loose titanium and aluminum particles at the interface mainly at the
      crestal cortical bone level. CONCLUSIONS: Shearing forces during the insertion
      procedure alters the surface of dental implants. Loose metal particles can be
      generated at bone-implant interface especially around surfaces composed mainly by
      peaks and with increased height parameters.

PMID- 24283456
TI  - A guide to writing case reports for the Journal of Medical Case Reports and
      BioMed Central Research Notes.
AB  - Case reports are a time-honored, important, integral, and accepted part of the
      medical literature. Both the Journal of Medical Case Reports and the Case Report
      section of BioMed Central Research Notes are committed to case report
      publication, and each have different criteria. Journal of Medical Case Reports
      was the world's first international, PubMed-listed medical journal devoted to
      publishing case reports from all clinical disciplines and was launched in 2007.
      The Case Report section of BioMed Central Research Notes was created and began
      publishing case reports in 2012. Between the two of them, thousands of peer
      reviewed case reports have now been published with a worldwide audience. Authors
      now also have Cases Database, a continually updated, freely accessible database
      of thousands of medical case reports from multiple publishers. This informal
      editorial outlines the process and mechanics of how and when to write a case
      report, and provides a brief look into the editorial process behind each of these
      complementary journals along with the author's anecdotes in the hope of inspiring
      all authors (both novice and experienced) to write and continue writing case
      reports of all specialties. Useful hyperlinks are embedded throughout for easy
      and quick reference to style guidelines for both journals. 

PMID- 24283457
TI  - Clusters [Ma(GaCp*)b(CNR)c] (M = Ni, Pd, Pt): synthesis, structure, and Ga/Zn
      exchange reactions.
AB  - Reactions of homoleptic isonitrile ligated complexes or clusters of d(10)-metals
      with the potent carbenoid donor ligand GaCp* are presented (Cp* =
      pentamethylcyclopentadienyl). Treatment of [Ni4(CNt-Bu)7], [{M(CNR)2}3] (M = Pd,
      Pt) and [Pd(CNR)2Me2] (R = t-Bu, Ph) with suitable amounts of GaCp* lead to the
      formation of the heteroleptic, tri- and tetranuclear clusters [Ni4(CNt
      Bu)7(GaCp*)3] (1), [{M(CNt-Bu)}3(GaCp*)4] (M = Pd: 2a, Pt: 2b), and
      [{Pd(CNR)}4(GaCp*)4] (R = t-Bu: 3a, Ph: 3b). The reactions involve isonitrile
      substitution reactions, GaCp* addition reactions, and cluster formation
      reactions. The new compounds were investigated for their ability to undergo Ga/Zn
      exchange reactions when treated with ZnMe2. The novel tetranuclear Zn-rich
      clusters [Ni4GaZn7(Cp*)2Me7(CNt-Bu)6] (4) and [{Pd(CNR)}4(ZnCp*)4(ZnMe)4] (R = t
      Bu: 5a, Ph: 5b) were obtained and isolated. The electronic situation and
      geometrical arrangement of atoms of all compounds will be presented and
      discussed. All new compounds are characterized by solution (1)H, (13)C NMR and IR
      spectroscopy, elemental analysis (EA), liquid injection field desorption
      ionization mass spectrometry (LIFDI-MS) as well as single crystal X-ray
      crystallography. 

PMID- 24283458
TI  - Remarkable prevalence of coeliac disease in patients with irritable bowel
      syndrome plus fibromyalgia in comparison with those with isolated irritable bowel
      syndrome: a case-finding study.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are
      two common central sensitization disorders frequently associated in the same
      patient, and some of these patients with IBS plus FMS (IBS/FMS) could actually be
      undiagnosed of coeliac disease (CD). The present study was an active case finding
      for CD in two IBS cohorts, one constituted by IBS/FMS subjects and the other by
      people with isolated IBS. METHODS: A total of 104 patients (89.4% females)
      fulfilling the 1990 ACR criteria for FMS and the Rome III criteria for IBS
      classification and 125 unrelated age- and sex-matched IBS patients without FMS
      underwent the following studies: haematological, coagulation and biochemistry
      tests, serological and genetic markers for CD (i.e., tissue transglutaminase 2
      (tTG-2) and major histocompatibility complex HLA-DQ2/HLA-DQ8), multiple gastric
      and duodenal biopsies, FMS tender points (TPs), Fibromyalgia Impact Questionnaire
      (FIQ), Health Assessment Questionnaire (HAQ), 36-Item Short Form Health Survey
      (SF-36) and Visual Analogue Scales (VASs) for tiredness and gastrointestinal
      complaints. RESULTS: As a whole, IBS/FMS patients scored much worse in quality of
      life and VAS scores than those with isolated IBS (P < 0.001). Seven subjects
      (6.7%) from the IBS/FMS group displayed HLA-DQ2/HLA-DQ8 positivity, high tTG-2
      serum levels and duodenal villous atrophy, concordant with CD. Interestingly
      enough, these seven patients were started on a gluten-free diet (GFD), showing a
      remarkable improvement in their digestive and systemic symptoms on follow-up.
      CONCLUSIONS: The findings of this screening indicate that a non-negligible
      percentage of IBS/FMS patients are CD patients, whose symptoms can improve and in
      whom long-term CD-related complications might possibly be prevented with a strict
      lifelong GFD.

PMID- 24283459
TI  - A specific miRNA signature promotes radioresistance of human cervical cancer
      cells.
AB  - BACKGROUND: The mechanisms responsible for cervical cancer radioresistance are
      still largely unexplored. The present study aimed to identify miRNAs associated
      with radioresistance of cervical cancer cells. METHODS: The radioresistant
      cervical cancer cell variants were established by repeated selection with
      irradiation. The miRNA profiles of radioresistant cells and their corresponding
      controls were analyzed and compared using microarray. Differentially expressed
      miRNAs were confirmed by quantitative real-time PCR. Cervical cancer cells were
      transfected with miRNA-specific mimics or inhibitors. Radiosensitivity of
      cervical cancer cells were determined using colony-forming assay. RESULTS: Among
      the differentially expressed miRNAs, 20 miRNAs showed the similar pattern of
      alteration (14 miRNAs were overexpressed whilst 6 were suppressed) in all three
      radioresistant cervical cancer cell variants compared to their controls. A miRNA
      signature consisting of 4 miRNAs (miR-630, miR-1246, miR-1290 and miR-3138)
      exhibited more than 5 folds of increase in radioresistant cells. Subsequent
      analysis revealed that these four miRNAs could be up-regulated in cervical cancer
      cells by radiation treatment in both time-dependent and dose-dependent manners.
      Ectopic expression of each of these 4 miRNAs can dramatically increase the
      survival fraction of irradiated cervical cancer cells. Moreover, inhibition of
      miR-630, one miRNA of the specific signature, could reverse radioresistance of
      cervical cancer cells. CONCLUSIONS: The present study indicated that miRNA is
      involved in radioresistance of human cervical cancer cells and that a specific
      miRNA signature consisting of miR-630, miR-1246, miR-1290 and miR-3138 could
      promote radioresistance of cervical cancer cells.

PMID- 24283460
TI  - Improved stability and antidiabetic potential of insulin containing folic acid
      functionalized polymer stabilized multilayered liposomes following oral
      administration.
AB  - The present study reports the folic acid (FA) functionalized insulin loaded
      stable liposomes with improved bioavailability following oral administration.
      Liposomes were stabilized by alternating coating of negatively charged
      poly(acrylic acid) (PAA) and positively charged poly(allyl amine) hydrochloride
      (PAH) over liposomes. Furthermore, folic acid was appended as targeting ligand by
      synthesizing folic acid-poly(allyl amine) hydrochloride conjugate. The insulin
      entrapped within the freeze-dried formulation was found stable both chemically as
      well as conformationally and developed formulation exhibited excellent stability
      in simulated biological fluids. Caco-2 cell and ex vivo intestinal uptake studies
      revealed higher uptake of folic acid functionalized layersomes in comparison with
      their plain counterparts. In vivo pharmacodynamic and pharmacokinetic studies
      further revealed almost double hypoglycemia and approximately 20% relative
      bioavailability in comparison with subcutaneously administered standard insulin
      solution. Overall the proposed strategy is expected to contribute significantly
      in the field of designing ligand-anchored, polyelectrolyte-based stable systems
      in drug delivery. 

PMID- 24283461
TI  - Diagnostic accuracy of malignant melanoma according to subtype.
AB  - BACKGROUND/OBJECTIVE: Although there has been improvement in clinical diagnosis
      of pigmented superficial spreading melanomas (SSM), less common melanoma subtypes
      have different clinical features and may be more difficult to diagnose. The
      objective was to assess diagnostic accuracy for different melanoma subtypes.
      METHODS: A retrospective review was made of a random selection of SSM, nodular
      melanomas (NM), desmoplastic melanomas (DM) and acral lentiginous melanomas (ALM)
      biopsied between February 2001 and May 2012 and referred to the Victorian
      Melanoma Service. Clinical differential diagnoses listed on pre-operative biopsy
      pathology request forms were recorded. Sensitivity for the diagnosis of melanoma
      was used as a marker of diagnostic accuracy. RESULTS: In total 111 SSM, 121 NM,
      43 DM and 30 ALM were biopsied by 222 clinicians. Whereas diagnostic sensitivity
      for SSM and ALM were similar (77%, 95% CI 69-85% and 73%, 95% CI 58-89%,
      respectively) diagnostic sensitivity was lower for NM (41%, 95% CI 33-50%) and DM
      (21%, 95% CI 9-33%). Both NM and DM were diagnosed at greater tumour thickness
      (median 3.0 mm and 4.0 mm) than SSM and ALM (both median 1.0 mm). Amelanosis was
      associated with lower diagnostic sensitivity for SSM (0 vs 82%, P < 0.01), NM (19
      vs 51%, P < 0.01) andDM (10 vs 32%, P = 0.07). Dermatologists were more accurate
      than non-dermatologists for NM (diagnostic sensitivity 57 vs 32%, P < 0.01) and
      ALM (diagnostic sensitivity 94 vs 43%, P = 0.02). CONCLUSIONS: Misdiagnosis of
      melanoma varies according to subtype and is particularly problematic for NM, DM
      and hypopigmented melanomas. Greater awareness of the different criteria required
      to diagnose these melanomas is needed.

PMID- 24283462
TI  - Homepages of German dental schools - a target group-oriented evaluation.
AB  - INTRODUCTION: The Internet represents the central communication medium in higher
      education. University applicants, students, teachers and scientists use the
      Internet when seeking information on medicine. The homepages of dental schools
      are not just sources of information, but also a means of presenting the school.
      No comparative studies have been undertaken concerning the content and extent of
      their Internet sites so far. METHODS: Based on the literature and assessments of
      medical school websites, 136 criteria were defined within the setting of a Delphi
      procedure and drawn upon for a standardised evaluation of the websites of all 30
      German dental schools. Structure and extent of the content of the websites were
      evaluated. Possible influencing factors, such as financial resources and number
      of applicants, were investigated. RESULTS: The results yielded by the homepages
      varied considerably. The best Internet site received 84% of the possible points,
      the poorest 38%. On average, 62% of the criteria were fulfilled. Influencing
      factors, such as the amount of funding by the particular state government, could
      not be detected. Two-thirds of the dental schools addressed students, three
      fourth teachers and scientists as target groups. More than 50% did not address
      applicants. Specific requirements regarding barrier-free accessibility of
      information were hardly met. CONCLUSIONS: Individual faculties already have
      homepages of a high quality; for others, there is a need for improvement. General
      recommendations for university websites should be discussed at the European level
      to ensure a uniform standard of quality. The criteria presented here offer
      faculties the possibility to reflect upon their own Internet sites.

PMID- 24283463
TI  - Chiral amide directed assembly of a diastereo- and enantiopure supramolecular
      host and its application to enantioselective catalysis of neutral substrates.
AB  - The synthesis of a novel supramolecular tetrahedral assembly of K12Ga4L6
      stoichiometry is reported. The newly designed chiral ligand exhibits high
      diastereoselective control during cluster formation, leading exclusively to a
      single diastereomer of the desired host. This new assembly also exhibits high
      stability toward oxidation or a low pH environment and is a more robust and
      efficient catalyst for asymmetric organic transformations of neutral substrates. 

PMID- 24283464
TI  - Female sexual dysfunction among Egyptian patients with chronic hepatitis C.
AB  - INTRODUCTION: Chronic hepatitis C is associated with many extrahepatic
      manifestations that impact and impair the quality of life. Hepatitis C virus
      (HCV) infection has a high prevalence in Egypt and carries with the diagnosis
      many social impacts and stigmatization correlates that further impair social
      function. This might negatively impact patients and their sexual function.
      Sexuality and sexual function have not been studied well in patients with HCV,
      especially in women. AIM: To investigate sexual dysfunction in Egyptian women
      with chronic hepatitis C. MAIN OUTCOME MEASURES: Female Sexual Function Index
      (FSFI) scores of patients with hepatitis C, both total and for individual
      domains, were compared with those of controls. METHODS: The self-administered
      FSFI questionnaire was completed by 112 sexually active female patients with
      chronic hepatitis C without liver cirrhosis prior to initiation of therapy by
      pegylated interferon and ribavirin. Their results were compared to those of 225
      age- and socioeconomic class-matched sexually active healthy females. RESULTS:
      Significantly more patients than controls had questionnaire scores below the
      threshold of female sexual dysfunction (FSD) (79% vs. 21%, P < 0.05), and the
      mean total score for the patients was significantly lower than that for controls
      (19.54 +/- 6.2 vs. 28.43 +/- 4.9 P < 0.001). The patients' scores in all domains
      of the questionnaire were significantly lower than those of the controls.
      CONCLUSION: Chronic hepatitis C negatively impacts female sexual function,
      affecting all domains of the sex cycle; this warrants further studies and needs
      to be addressed as part of a comprehensive therapy plan to improve patients'
      quality of life.

PMID- 24283465
TI  - Four-component relativistic density functional theory calculations of NMR
      shielding tensors for paramagnetic systems.
AB  - A four-component relativistic method for the calculation of NMR shielding
      constants of paramagnetic doublet systems has been developed and implemented in
      the ReSpect program package. The method uses a Kramer unrestricted noncollinear
      formulation of density functional theory (DFT), providing the best DFT framework
      for property calculations of open-shell species. The evaluation of paramagnetic
      nuclear magnetic resonance (pNMR) tensors reduces to the calculation of
      electronic g tensors, hyperfine coupling tensors, and NMR shielding tensors. For
      all properties, modern four-component formulations were adopted. The use of both
      restricted kinetically and magnetically balanced basis sets along with gauge
      including atomic orbitals ensures rapid basis-set convergence. These approaches
      are exact in the framework of the Dirac-Coulomb Hamiltonian, thus providing
      useful reference data for more approximate methods. Benchmark calculations on
      Ru(III) complexes demonstrate good performance of the method in reproducing
      experimental data and also its applicability to chemically relevant medium-sized
      systems. Decomposition of the temperature-dependent part of the pNMR tensor into
      the traditional contact and pseudocontact terms is proposed. 

PMID- 24283466
TI  - Strategies toward enhanced low-pressure volumetric hydrogen storage in nanoporous
      cryoadsorbents.
AB  - The volumetric hydrogen capacity remains one of the most challenging criteria for
      on-board hydrogen storage system requirements. Here a new concept for hydrogen
      storage of porous aromatic frameworks (PAFs) impregnated with lithium-decorated
      fullerenes (Li6C60) is described. The loading of Li6C60 and the effect on the
      adsorption of hydrogen (H2) has been investigated by molecular simulation. It is
      shown that the incorporation of Li6C60 can enhance the volumetric capacity of H2
      from 12 to 44 g L(-1), a 260% increase at 10 bar and 77 K. The impregnation of
      Li6C60 increases the heat of adsorption and surface area at the cost of the
      available pore volume. However, the increase in adsorbed hydrogen outweighs any
      pore volume loss under optimized Li6C60 loading and operating conditions. In
      addition, the H2 volumetric uptake is shown to correlate with the volumetric
      surface area at all pressures whereas the H2 gravimetric uptake correlates with
      the heat of adsorption at low pressures, surface area at moderate pressures, and
      pore volume at high pressures. 

PMID- 24283467
TI  - Electric-field control of ferromagnetism in a nanocomposite via a ZnO phase.
AB  - La2CoMnO6 (LcmO)-ZnO nanocomposite thin films grown on SrTiO3 and Nb-SrTiO3 (001)
      are investigated. The films grow in the form of self-assembled epitaxial
      vertically aligned structures. We show that, at 120 K, an electric field applied
      across the nanocomposite reversibly alters magnetic properties of LcmO. The
      effect is consistent with charge-mediated coupling between magnetism and an
      electric field that can be induced by changes in ion valences. 

PMID- 24283468
TI  - Nonrandom genotype distribution among floral hosts contributes to local and
      regional genetic diversity in the nectar-living yeast Metschnikowia reukaufii.
AB  - Environmental heterogeneity has been often suggested as a major driving force
      preserving genetic variation in clonal microorganisms. This study examines this
      hypothesis for the specialized nectar-dwelling, clonal yeast Metschnikowia
      reukaufii (Ascomycota, Saccharomycetales). We examined whether M. reukaufii
      subpopulations associated with flowers of different host plant species, and
      different individuals of the same host species, differed in genetic
      characteristics. Amplified fragment length polymorphisms (AFLP) fingerprints of
      M. reukaufii strains isolated from floral nectar of different host species and
      individuals sampled at different spatial scales revealed a strong host-mediated
      component of genetic and genotypic diversity at all scales considered. Genotypes
      were nonrandomly distributed among flowers of different species and, in the case
      of the single host species studied in detail (Helleborus foetidus), also among
      flowers of conspecific individuals coexisting locally. These host-mediated
      patterns of genetic structuring are compatible with those expected under the
      diversifying selection hypothesis for the maintenance of local and regional
      genetic diversity in clonal organisms. It is proposed that a combination of
      intrafloral selection and biased pollinator-mediated migration may ultimately
      account for observed host-mediated genetic structuring in populations of M.
      reukaufii. 

PMID- 24283469
TI  - 'Time to TASH': how long does complete score calculation take to assess major
      trauma hemorrhage?

PMID- 24283471
TI  - Exploiting quantum interference in dye sensitized solar cells.
AB  - A strategy to hinder the charge recombination process in dye sensitized solar
      cells is developed in analogy with similar approaches to modulate charge
      transport across nanostructures. The system studied is a TiO2 (anatase)
      chromophore interface, with an unsaturated carbon bridge connecting the two
      subunits. A theory for nonadiabatic electron transfer is employed in order to
      take explicitly into account the contribution from the bridge states mediating
      the process. If a cross-conjugated fragment is present in the bridge, it is
      possible to suppress the charge recombination by negative interference of the
      possible tunnelling path. Calculations carried out on realistic molecules at the
      DFT level of theory show how the recombination lifetime can be modulated by
      changes in the electron-withdrawing (donating) character of the groups connected
      to the cross-conjugated bridge. Tight binding calculations are employed to
      support the interpretation of the atomistic simulations. 

PMID- 24283472
TI  - High-density genome-wide association mapping implicates an F-box encoding gene in
      Medicago truncatula resistance to Aphanomyces euteiches.
AB  - * The use of quantitative disease resistance (QDR) is a promising strategy for
      promoting durable resistance to plant pathogens, but genes involved in QDR are
      largely unknown. To identify genetic components and accelerate improvement of QDR
      in legumes to the root pathogen Aphanomyces euteiches, we took advantage of both
      the recently generated massive genomic data for Medicago truncatula and natural
      variation of this model legume. * A high-density (~5.1 million single nucleotide
      polymorphisms (SNPs)) genome-wide association study (GWAS) was performed with
      both in vitro and glasshouse phenotyping data collected for 179 lines. * GWAS
      identified several candidate genes and pinpointed two independent major loci on
      the top of chromosome 3 that were detected in both phenotyping methods. Candidate
      SNPs in the most significant locus (sigma(A)2= 23%) were in the promoter and
      coding regions of an F-box protein coding gene. Subsequent qRT-PCR and
      bioinformatic analyses performed on 20 lines demonstrated that resistance is
      associated with mutations directly affecting the interaction domain of the F-box
      protein rather than gene expression. * These results refine the position of
      previously identified QTL to specific candidate genes, suggest potential
      molecular mechanisms, and identify new loci explaining QDR against A. euteiches.

PMID- 24283470
TI  - The effect of relaxin on the musculoskeletal system.
AB  - Relaxin is a hormone structurally related to insulin and insulin-like growth
      factor, which exerts its regulatory effect on the musculoskeletal and other
      systems through binding to its receptor in various tissues, mediated by different
      signaling pathways. Relaxin alters the properties of cartilage and tendon by
      activating collagenase. This hormone is also involved in bone remodeling and
      healing of injured ligaments and skeletal muscle. In this review, we have
      summarized the literature on the effect of relaxin in musculoskeletal system to
      provide a broad perspective for future studies in this field. 

PMID- 24283473
TI  - Self-doped rutile titania with high performance for direct and ultrafast assay of
      H2O2.
AB  - Detection of H2O2 is important for the applications in environmental protection,
      pharmaceutical industries, food production, and clinical control. Current
      colorimetric assay of H2O2 based on enzyme or nanomaterials always needs TMB or
      other peroxidase substrate as coloration species. Furthermore, the corresponding
      response time including incubation process is in order of minute. In this study,
      we report on the synthesis of heavily Ti(3+)-doped TiO2 composed of spherelike
      nanoparticles by pulsed laser ablation method. This TiO2 can directly detect H2O2
      without using TMB or any other peroxidase substrate and is free from incubation
      process. In addition, the detection sensitivity is compatible with or better than
      that of the natural enzyme or other nanomaterials. Hence, the self-doped TiO2
      nanoparticles provide a novel, direct, ultrafast approach for H2O2 assay
      application. 

PMID- 24283474
TI  - Lung alterations following single or multiple low-dose carbon black nanoparticle
      aspirations in mice.
AB  - Carbon black nanoparticle (CBNP) applications in high doses have been shown to be
      harmful to the lung. It is postulated that even small, environmentally relevant
      concentrations induce changes on lung homeostasis. The present study determined
      the impact of low-dose single and multiple CBNP (Printex 90) applications on
      mouse alveolar cell metabolism, especially inflammatory and oxidative stress
      parameters. Nanoparticles were administered to mice by a single or 8
      oropharyngeal aspirations at wk 1, 2, 3, 5, 7, 9, 11, and 12 using 7 MUg Printex
      90, 7 MUg DQ12 quartz (positive control), with water vehicle and saline as
      negative controls. After 2 d or 3 mo lung function was analyzed. Further lung
      histology, bronchoalveolar lavage fluid (BALF) parameters, and mRNA expression of
      cytokines and antioxidants enzymes in type II pneumocytes were measured on d 3 or
      after 3 mo. Single low-dose Printex 90 application induced no marked alterations
      in lung functions or BALF phospholipid levels but significant decrease in
      superoxide dismutase 2 and numerically elevated glutathione peroxidase 3 mRNA
      expression levels in type II pneumocytes. Multiple CBNP applications produced
      reduced lung function, collagen accumulation, elevated phospholipid levels in
      BALF, and a massive infiltration of macrophages. Type II pneumocyte mRNA
      expression of antioxidative enzymes remained unchanged throughout the subchronic
      experiment, but showed a significant decrease in interleukin (IL)-6Ralpha mRNA
      expression. This study demonstrates that an environmentally relevant CBNP
      concentration induced an acute inflammatory response, an effect that is
      exacerbated throughout the subchronic duration. 

PMID- 24283475
TI  - Effects of oral exposure to arsenobetaine during pregnancy and lactation in
      Sprague-Dawley rats.
AB  - Arsenobetaine (ASB) is the major form of arsenic (As) in seafood sources such as
      molluscs and fish. Limited data demonstrated that ASB toxicity in mammals is
      minimal; however, data on possible reproductive effects are lacking. This study
      investigated the tissue distribution and developmental effects of ASB during
      pregnancy, early postnatal life, and development to adulthood. Pregnant rats were
      randomly assigned to 3 cohorts and gavaged daily from gestational day 8 (GD8)
      with ASB in deionized water at 0, 0.1, 1, or 10 mg/kg body weight (bw)/d. Cohort
      1 dams were sacrificed on GD20 (n = 6 per dose group), cohort 2 dams and pups
      were sacrificed on postnatal day 13 (PND13; n = 4 dams per dose group), and
      cohort 3 pups (n = 2 dams per dose group) were sacrificed on PND90. Residue
      analysis detected significant levels of ASB in livers of cohort 1 dams and lower
      levels in cohort 1 GD20 fetuses, as well as in cohort 2 male and female
      offspring, indicating placental transfer from the maternal circulation in utero.
      Trace amounts of ASB in dams' milk were found only in the 10-mg/kg bw/d dose
      cohort 2 (PND13), demonstrating that lactational transfer was limited. ASB levels
      in liver varied during pregnancy, lactation, and postweaning, with levels falling
      rapidly as these physiological states progress. Although transfer of ASB through
      the placenta to the fetuses and to a limited extent through milk was confirmed,
      ASB exposure during pregnancy and lactation appeared to produce no teratogenic or
      deleterious effects on reproductive development. 

PMID- 24283476
TI  - Sodium copper chlorophyllin (SCC) induces genetic damage in postmeiotic and
      somatic wing cells of Drosophila melanogaster.
AB  - There is no apparent evidence to indicate that sodium copper chlorophyllin (SCC)
      is mutagenic. The aim of the present study was thus to determine the mutagenic
      effect of SCC, in postmeiotic germ cells of the adult male Drosophila. This
      investigation was based on the ability to examine whether SCC induced sex-linked
      recessive lethal mutations (SLRL), as well as the somatic mutation and
      recombination test (SMART). Four different SCC concentrations were used: 0, 45,
      69, 80, and 100 mM. For SLRL, two broods were generated to test sperm and
      primarily spermatids. Results showed a significant frequency of recessive lethal
      mutations compared with control sperm cells with SCC at 69, 80, and 100 mM. In
      contrast, the frequency of somatic mutations rose by 0.21 only with 100 mM of
      SCC. These findings provide evidence that SCC is a weak mutagen in both cell
      lines. The differential response may be attributed to repair mechanisms that are
      active in somatic cells but almost absent in germ cells. 

PMID- 24283477
TI  - Differential modulation of xenobiotic-metabolizing enzymes in rats following
      single and concurrent exposure to chlorpyrifos, arsenic, and ascorbic acid.
AB  - The present study was undertaken to evaluate the subacute toxicity of arsenic
      (As) and chlorpyrifos (CPF) alone or in combination. In addition, the
      ameliorative effect of ascorbic acid on As and/or CPF-induced hepatic microsomal
      xenobiotic metabolizing enzymes in rats was examined. Rats were divided into 9
      groups of 6 animals each: control (deionized water), vehicle control (groundnut
      oil), ascorbic acid (100 mg/kg body weight), As (40 ppm in water), CPF (5 mg/kg
      body weight), As (40 ppm) + CPF (5 mg/kg body weight), As + ascorbic acid, CPF +
      ascorbic acid, and As + CPF + ascorbic acid. After 28 d of exposure, rats were
      sacrificed and liver was extracted for isolation of hepatic microsomes. Exposure
      to As or CPF alone as well as both of these in combination significantly altered
      microsomal proteins and activity of phase I and phase II xenobiotic-metabolizing
      enzymes. Cytochrome P-450 and cytochrome b 5 levels and activities of aniline p
      hydroxylase (APH) and uridine diphosphate glucuronosyltransferase (UGT) were
      significantly decreased in groups treated with As, CPF, and As plus CPF, while
      glutathione S-transferase (GST) was not markedly altered. Enzymatic activity of
      aminopyrine N-demethylase (ANDM) was also significantly reduced in As- and CPF
      only groups. Co-administration of ascorbic acid effectively countered the As- and
      CPF-induced alterations in xenobiotic-metabolizing enzymes. 

PMID- 24283478
TI  - Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL
      4/IL-13 antagonist in asthma.
AB  - INTRODUCTION: Asthma markedly diminishes quality of life due to limited activity,
      absences from work or school and hospitalizations. Patients with severe asthma
      which are not controlled despite taking effective therapy are most in need of new
      treatment approaches. IL-13 was demonstrated as 'central mediator of allergic
      asthma'. AREAS COVERED: IL-13 has been implicated in the pathogenesis of asthma,
      idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial
      biopsy samples remain elevated in severe asthma despite the use of inhaled and
      systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid
      resistance. Periostin enhances profibrotic TGF-beta signaling in subepithelial
      fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to
      secrete periostin. Periostin may be a biomarker for Th2 induced airway
      inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab
      improved lung function in asthmatics who were symptomatic despite treatment with
      long acting beta agonist and inhaled corticosteroids and provided benefit in the
      treatment of severe uncontrolled asthma. EXPERT OPINION: Lebrikizumab block IL-13
      signaling through the IL-13Ralpha1/IL-4Ralpha receptor. There was a larger
      reduction in FENO in the high periostin subgroup than in the low periostin
      subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the
      lebrikizumab group.

PMID- 24283479
TI  - Cerebral venous and sinus thrombosis - an update.

PMID- 24283480
TI  - Diagnostic problems in "clinically definite" multiple sclerosis patients with
      normal CSF and multiple MRI abnormalities.
AB  - Among patients who underwent cerebrospinal fluid (CSF) and magnetic resonance
      imaging (MRI) examination during a 5-year period, we found 18 patients at the
      multiple sclerosis center of the University of Rome and clinically definite
      multiple sclerosis, MRI white matter abnormalities, normal CSF examination, a
      disease duration of at least 1 year and an upper age of < 45 years at onset These
      patients were examined again with a variety of tests screening for different
      diseases mimicking multiple sclerosis. Alternative diagnoses reached after
      laboratory tests were: Lyme disease, two cases of vasculitis, mitochondrial
      encephalomyopathy, multiple ischemic lesions caused by atrial septum aneurysm and
      olivopontocerebellar atrophy. Hence, six of these 18 patients had a final
      diagnosis other than multiple sclerosis, while 12 remained with a final diagnosis
      of "MS with normal CSF". Our study suggests that in patients with a clinical
      picture of multiple sclerosis and disseminated white matter MRI lesions but no
      CSF abnormalities, the classical clinical criteria may not be sufficiently
      specific, unless confirmed by a very prolonged clinical history with repeated
      MRI. 

PMID- 24283481
TI  - Endothelin-like immunoreactivity is expressed in reactive astrocytes in cases of
      cerebral infarcts and lacunes.
AB  - The avidin-biotin peroxidase complex method and a polyclonal antiserum were used
      to investigate the expression of endothelin-like immunoreactivity in human
      autopsy cases presenting cerebral infarcts and lacunes. Cases with recent
      infarcts showed loss of immunoreactivity in neurons of the infarcts.
      Immunoreactive granules started to appear in astrocytic endfeet of microvessels
      of the border zones. Later on, numerous reactive astrocytes presented
      immunoreactivity in the entire cell body. Cases with old infarcts had a more
      widespread presence of astrocytes with endothelin-like immunoreactivity around
      the lesions. Macrophages particularly of old infarcts showed a strong
      immunoreactivity. Cases with old lacunes presented numerous reactive fibrillary
      astrocytes with endothelin-like immunoreactivity in the cell body and the
      processes. Astrocytes of controls showing endothelin-like immunoreactivity were
      very rare and such cells were usually confined to the molecular layer of the
      cerebral cortex. The endothelin-like immunoreactivity in astrocytes and
      macrophages of cases with cerebrovascular diseases probably reflects an increased
      intracellular content of endothelin. If this compound is released from such cells
      it may act as a mitogen and influence microcirculation by inducing
      vasoconstriction of intracerebral arterioles.- 

PMID- 24283482
TI  - Acetylsalicylic acid inhibits cerebral cortical vasodilatation caused by superior
      sagittal sinus stimulation in the cat*.
AB  - Acetylsalicylic acid (ASA; aspirin) is one of the most widely used pain reliefs
      in the world and is certainly effective in the treatment of acute attacks of
      migraine of moderate severity. It has usually been considered that the action of
      ASA in migraine is related to peripheral inhibition of mediators of inflammation.
      Migraine involves episodic head pain that is thought generally to involve
      intracranial pain structures innervated by the ophthalmic (first) division of the
      trigeminal nerve, particularly vascular structures that have come to be known as
      the trigeminovascular system. In this study the effect of ASA on the
      cerebrovascular effects of the trigeminovascular system were assessed directly
      with measurements of cerebral blood flow. The trigeminovascular system was
      activated by stimulation of the superior sagittal sinus (SSS), a midline large
      venous sinus that is pain sensitive in humans. The SSS was stimulated
      electrically and cerebral blood flow measured using laser Doppler flowmetry
      (CBFLDF ). Stimulation of the SSS resulted in a stimulus-locked frequency
      dependent increase in CBFLDF that reached a mean maximum at 2 Hz with a 60 +/- 6%
      reduction in calculated cerebrovascuiar resistance. Administration of ASA (30
      mg/kg i.v.) resulted in a small non-sustained increase in blood pressure but no
      change in resting CBFLDF . The CBFLDF response to SSS stimulation was reduced at
      all but one frequency of stimulation to a maximum of a 43 +/- 10% reduction in
      cerebrovascular resistance. Since electrical stimulation involves consecutive
      depolarization of trigeminovascular axons and bypasses the peripheral nerve
      vessel interaction it is likely that this effect of ASA is mediated in the
      central nervous system. Such a possibility draws attention to a possibly novel
      therapeutic locus of action for ASA and to the importance of central nervous
      system processing of trigeminovascular inputs that are integral to the clinical
      expression of migraine. 

PMID- 24283483
TI  - Quantified electroencephalographic changes in Parkinson's disease with and
      without dementia.
AB  - We examined the presence of quantified electroencephalographic (qEEG) differences
      between Parkinson's disease (PD) patients with and without dementia, and a group
      of age-comparable normal controls. While there were no significant differences in
      relative power in any of the qEEG bands between PD patients without dementia and
      normal controls, PD patients showed a significantly greater reactivity in the
      alpha band. On the other hand, PD patients with dementia showed significantly
      less alpha and more theta relative power than both the normal control and the PD
      without dementia groups. When PD patients with dementia were compared with a
      group of patients with Alzheimer's disease (AD) and a similar severity of
      dementia, no significant between-group differences were found in any of the qEEG
      bands. In conclusion, while our study demonstrated no significant qEEG
      differences between non-demented PD patients and normal controls, PD patients
      with dementia showed qEEG changes similar to those observed in patients with AD. 

PMID- 24283484
TI  - Impaired colour discrimination in Huntington's disease.
AB  - Colour discrimination and visual contrast perception were investigated in 18
      patients with Huntington's disease (HD) and in 18 age- and sex-matched healthy
      volunteers using the Farnsworth-Munsell 100 Hue test (FM) and stationary contrast
      targets. The mean total error score (MTES) and the partial scores for the "red
      green" and the "blue-yellow" axes in the FM of the patients with HD were
      significantly elevated as compared to controls (MTES in HD: 113.0 +/- 90.8; MTES
      in controls: 19.2 +/- 8.8). The spatial contrast sensitivity in HD patients was
      normal. The colour perception dysfunction indicates that the visual system is
      affected in HD. The visual disorder may be related to an imbalance of certain
      neurotransmitters in the visual system of HD patients. Possible anatomical sites
      of the dysfunction responsible for colour discrimination abnormalities could be
      the retinal cone system and/or impaired parvocellular central visual pathways in
      HD. 

PMID- 24283485
TI  - Everyday memory impairment, neuroradiological findings and physical disability in
      multiple sclerosis.
AB  - Thirty-five multiple sclerosis (MS) patients diagnosed according to the Poser
      criteria were examined in a variety of cognition and memory tasks. Their
      performance was compared to age- and gender-matched healthy individuals. While
      there was no difference in overall intellectual performance and short-term memory
      between the MS group and control subjects, the patient group showed significant
      deficits in several everyday memory tasks including story recall, object and face
      recognition, procedural, topographical and prospective memory tasks. An intra
      group comparison in the MS cohort revealed that those patients with a chronic
      progressive MS course exhibited the most substantial everyday memory impairments
      and highest EDSS scores. These findings coincide with the neuroradiological,
      semiquantitative lesion analysis which was also performed. In this analysis, the
      latter MS subgroup also had the highest lesion score, as a sign of an overall
      brain involvement. 

PMID- 24283486
TI  - Bilateral thalamic damage, cortical hypometabolism and behavioural disturbances.
AB  - Thalamic damage could be responsible for reduced metabolism in anterior cortical
      areas. In order to investigate an anatomical lesion and impairment of regional
      blood flow (rCBF) in distant cortical areas, we studied by magnetic resonance
      imaging (MRI) and single photon emission computed tomography (SPECT) a patient
      with bilateral thalamic infarction, who presented with sudden consciousness
      impairment, drowsiness, gaze paralysis, dysphagia and bilateral Babinski sign.
      Three weeks later the neurological symptoms disappeared, but a severe mental
      deterioration was evident MRI showed thalamic bilateral damage of posterior and
      medial areas, involving part of the pulvinar, more evident for the right
      thalamus. A (99m) Tc-HMPAO SPECT showed a decrease of rCBF over frontal and
      parietal regions, more evident for the right hemisphere. Six months later a
      severe memory impairment was still evident and MRI and SPECT picture were
      unchanged. The persistent memory defect could be related to a loss of cortical
      activation following the thalamic damage. The absence of primary lesions of
      cortical regions on CT scan and MRI and the neuroanatomical considerations on the
      diffuse projections running from medial nuclei and pulvinar to large parts of
      anterior neocortex supported this hypothesis. 

PMID- 24283487
TI  - Neurosonographic findings in dementia.
AB  - We performed neurosonographic examinations in 19 patients with vascular dementia
      (VD) and compared these findings with those in 21 patients with dementia of the
      Alzheimer type (DAT) and in 20 controls. There were no significant differences in
      age and sex among these three subject groups. The severity of dementia quantified
      by the Mini-Mental State Examination and Mattis Dementia Rating Scale did not
      reveal significant differences between VD and DAT. We found that carotid stenosis
      > 50% or occlusion was more frequent in VD compared to controls. The mean flow
      velocities of both the middle cerebral artery (MCA) and the basilar artery (BA)
      were decreased in VD and DAT compared with controls. This decrease was
      statistically significant for left MCA, but not for right MCA and BA. However, we
      did not find any significant differences between VD and DAT for the mean flow
      velocities of both MCA and BA. 

PMID- 24283488
TI  - Simvastatin-induced rhabdomyolysis.
AB  - At a time of increasing use of simvastatin and other "statin" drugs for
      cholesterol lowering, we report a case of simvastatin-induced acute massive
      rhabdomyolysis with renal failure in a woman with primary biliary cirrhosis,
      occurring 2 years after starting the drug. The differential diagnosis is
      highlighted and the literature reviewed. 

PMID- 24283489
TI  - Loss of taste and carbamazepine.
AB  - Carbamazepine is the drug of choice for many partial and generalized seizures.
      Neurotoxic manifestations are the most common side effect. We present an
      unrecognized neurological complication associated with carbamazepine occurring
      probably as an idiosyncratic event. 

PMID- 24283490
TI  - Topological structural alerts modulations of mammalian cell mutagenicity for
      halogenated derivatives.
AB  - Genotoxicity is a key toxicity endpoint for current regulatory requirements
      regarding new and existing chemicals. However, genotoxicity testing is time
      consuming and costly, and involves the use of laboratory animals. This has
      motivated the development of computational approaches, designed to predict
      genotoxicity without the need to conduct laboratory tests. Currently, many
      existing computational methods, like quantitative structure-activity relationship
      (QSAR) models, provide limited information about the possible mechanisms involved
      in mutagenicity or predictions based on structural alerts (SAs) do not take
      statistical models into account. This paper describes an attempt to address this
      problem by using the TOPological Substructural MOlecular Design (TOPS-MODE)
      approach to develop and validate improved QSAR models for predicting the
      mutagenicity of a range of halogenated derivatives. Our most predictive model has
      an accuracy of 94.12%, exhibits excellent cross-validation and external set
      statistics. A reasonable interpretation of the model in term of SAs was achieved
      by means of bond contributions to activity. The results obtained led to the
      following conclusions: primary halogenated derivatives are more mutagenic than
      secondary ones; and substitution of chlorine by bromine increases mutagenicity
      while polyhalogenation decreases activity. The paper demonstrates the potential
      of the TOPS-MODE approach in developing QSAR models for identifying structural
      alerts for mutagenicity, combining high predictivity with relevant mechanistic
      interpretation. 

PMID- 24283491
TI  - Effects of emotion and emotional valence on the neural correlates of episodic
      memory search and elaboration.
AB  - Successful retrieval of an event includes an initial search phase in which the
      information is accessed and a subsequent elaboration phase in which an individual
      expands on event details. Traditionally, functional neuroimaging studies
      examining episodic memory retrieval either have not made a distinction between
      these two phases or have focused on the initial search process. The current study
      used an extended retrieval trial to compare the neural correlates of search and
      elaboration and to examine the effects of emotion on each phase. Before scanning,
      participants encoded positive, negative, and neutral images paired with neutral
      titles. After a 30-min delay, participants engaged in a scanned recognition task
      in which they viewed the neutral titles and indicated whether the title had been
      presented with an image during the study phase. Retrieval was divided into an
      initial memory search and a subsequent 5-sec elaboration phase. The current study
      identified neural differences between the search and elaboration phases, with
      search being associated with widespread bilateral activations across the entire
      cortex and elaboration primarily being associated with increased activity in the
      medial pFC. The emotionality of the retrieval target was more influential during
      search relative to elaboration. However, valence influenced when the effect of
      emotion was greatest, with search engaging many more regions for positive events
      than negative ones, but elaboration engaging the dorsomedial pFC more for
      negative events than positive events. 

PMID- 24283493
TI  - Neural correlates of state- and strength-based perception.
AB  - Perceptual judgments can be based on two kinds of information: state-based
      perception of specific, detailed visual information, or strength-based perception
      of global or relational information. State-based perception is discrete in the
      sense that it either occurs or fails, whereas strength-based perception is
      continuously graded from weak to strong. The functional characteristics of these
      types of perception have been examined in some detail, but whether state- and
      strength-based perception are supported by different brain regions has been
      largely unexplored. A consideration of empirical work and recent theoretical
      proposals suggests that parietal and occipito-temporal regions may be
      differentially associated with state- and strength-based signals, respectively.
      We tested this parietal/occipito-temporal state/strength hypothesis using fMRI
      and a visual perception task that allows separation of state- and strength-based
      perception. Participants made same/different judgments on pairs of faces and
      scenes using a 6-point confidence scale where "6" responses indicated a state of
      perceiving specific details that had changed, and "1" to "5" responses indicated
      judgments based on varying strength of relational match/mismatch. Regions in the
      lateral and medial posterior parietal cortex (supramarginal gyrus, posterior
      cingulate cortex, and precuneus) were sensitive to state-based perception and
      were not modulated by varying levels of strength-based perception. In contrast,
      bilateral fusiform gyrus activation was increased for strength-based "different"
      responses compared with misses and did not show state-based effects. Finally, the
      lateral occipital complex showed increased activation for state-based responses
      and additionally showed graded activation across levels of strength-based
      perception. These results offer support for a state/strength distinction between
      parietal and temporal regions, with the lateral occipital complex at the
      intersection of state- and strength-based processing. 

PMID- 24283492
TI  - Conceptual and data-based investigation of genetic influences and brain
      asymmetry: a twin study of multiple structural phenotypes.
AB  - Right-left regional cerebral differences are a feature of the human brain linked
      to functional abilities, aging, and neurodevelopmental and mental disorders. The
      role of genetic factors in structural asymmetry has been incompletely studied. We
      analyzed data from 515 individuals (130 monozygotic twin pairs, 97 dizygotic
      pairs, and 61 unpaired twins) from the Vietnam Era Twin Study of Aging to answer
      three questions about genetic determinants of brain structural asymmetry: First,
      does the magnitude of heritability differ for homologous regions in each
      hemisphere? Despite adequate power to detect regional differences, heritability
      estimates were not significantly larger in one hemisphere versus the other,
      except left > right inferior lateral ventricle heritability. Second, do different
      genetic factors influence left and right hemisphere size in homologous regions?
      Interhemispheric genetic correlations were high and significant; in only two
      subcortical regions (pallidum and accumbens) did the estimate statistically
      differ from 1.0. Thus, there was little evidence for different genetic influences
      on left and right hemisphere regions. Third, to what extent do genetic factors
      influence variability in left-right size differences? There was no evidence that
      variation in asymmetry (i.e., the size difference) of left and right homologous
      regions was genetically determined, except in pallidum and accumbens. Our
      findings suggest that genetic factors do not play a significant role in
      determining individual variation in the degree of regional cortical size
      asymmetries measured with MRI, although they may do so for volume of some
      subcortical structures. Despite varying interpretations of existing data, we view
      the present results as consistent with previous findings. 

PMID- 24283494
TI  - Seeing without knowing: neural signatures of perceptual inference in the absence
      of report.
AB  - Every day, we experience a rich and complex visual world. Our brain constantly
      translates meaningless fragmented input into coherent objects and scenes.
      However, our attentional capabilities are limited, and we can only report the few
      items that we happen to attend to. So what happens to items that are not
      cognitively accessed? Do these remain fragmentary and meaningless? Or are they
      processed up to a level where perceptual inferences take place about image
      composition? To investigate this, we recorded brain activity using fMRI while
      participants viewed images containing a Kanizsa figure, an illusion in which an
      object is perceived by means of perceptual inference. Participants were presented
      with the Kanizsa figure and three matched nonillusory control figures while they
      were engaged in an attentionally demanding distractor task. After the task, one
      group of participants was unable to identify the Kanizsa figure in a forced
      choice decision task; hence, they were "inattentionally blind." A second group
      had no trouble identifying the Kanizsa figure. Interestingly, the neural
      signature that was unique to the processing of the Kanizsa figure was present in
      both groups. Moreover, within-subject multivoxel pattern analysis showed that the
      neural signature of unreported Kanizsa figures could be used to classify reported
      Kanizsa figures and that this cross-report classification worked better for the
      Kanizsa condition than for the control conditions. Together, these results
      suggest that stimuli that are not cognitively accessed are processed up to levels
      of perceptual interpretation. 

PMID- 24283495
TI  - Functional connectivity relationships predict similarities in task activation and
      pattern information during associative memory encoding.
AB  - Neural systems may be characterized by measuring functional interactions in the
      healthy brain, but it is unclear whether components of systems defined in this
      way share functional properties. For instance, within the medial temporal lobes
      (MTL), different subregions show different patterns of cortical connectivity. It
      is unknown, however, whether these intrinsic connections predict similarities in
      how these regions respond during memory encoding. Here, we defined brain networks
      using resting state functional connectivity (RSFC) then quantified the functional
      similarity of regions within each network during an associative memory encoding
      task. Results showed that anterior MTL regions affiliated with a network of
      anterior temporal cortical regions, whereas posterior MTL regions affiliated with
      a network of posterior medial cortical regions. Importantly, these connectivity
      relationships also predicted similarities among regions during the associative
      memory task. Both in terms of task-evoked activation and trial-specific
      information carried in multivoxel patterns, regions within each network were more
      similar to one another than were regions in different networks. These findings
      suggest that functional heterogeneity among MTL subregions may be related to
      their participation in distinct large-scale cortical systems involved in memory.
      At a more general level, the results suggest that components of neural systems
      defined on the basis of RSFC share similar functional properties in terms of
      recruitment during cognitive tasks and information carried in voxel patterns. 

PMID- 24283496
TI  - The CARE (CAse REport) guidelines and the standardization of case reports.
AB  - Case reports comprise the core of Journal of Medical Case Reports, are a time
      honored tradition firmly established within the medical literature, and represent
      a growing importance of valuable clinical medical information in our modern
      information-flowing times. While there is already a body of published literature
      on how and when to write a case report and both Journal of Medical Case Reports
      and BioMed Central make known their own criteria, case report quality across all
      of the medical literature is still variable. Additionally, although health
      reporting agencies do have standardization guidelines for other aspects of health
      care reporting, there has never been an organizational body responsible for
      international standardization of how to write a case report. With the newly
      published CARE (CAse REport) guidelines, Gagnier and colleagues hope to change
      this. This editorial serves as a brief introduction to the CARE guidelines and
      briefly examines the proposed standardization of case reports. We invite feedback
      on the CARE guidelines from all of our readers and encourage their trial run
      implementation by our own case report authors. 

PMID- 24283497
TI  - Bone Formation in a Local Defect around Dental Implants Coated with Extracellular
      Matrix Components.
AB  - PURPOSE: The coating of implant surfaces with components of the extracellular
      matrix offers an approach to influence peri-implant bone healing. In this study,
      bone healing around coated implants is analyzed in a peri-implant defect model.
      MATERIALS AND METHODS: Eight months after extraction of the premolar teeth, six
      dogs received 48 implants (eight per animal) in the mandible. Implant surfaces
      were sandblasted and acid-etched, and some were additionally coated with collagen
      type II and chondroitin sulfate (collagen/CS). On each side of the mandible,
      implants either had no peri-implant defect (control side) or a vertical defect of
      5 mm in depth and 0.5, 1.0, or 2.0 mm in width. Implants healed submerged for 8
      weeks. Fluorochrome staining, histology, and histomorphometry were used to
      analyze implant osseointegration. RESULTS: Fluorochrome labels showed an
      increased mineralization around collagen/CS-coated surfaces at 4 weeks (p =
      .031). Histomorphometry generally showed lower vertical and horizontal bone
      apposition with increasing gap size for both surface types. In gapless sites and
      0.5-mm gaps, collagen/CS coated implants showed increased bone volume in areas
      directly adjacent to the implant, in comparison with uncoated implants (p < .05).
      CONCLUSION: The width of the peri-implant gap influences peri-implant bone
      formation. Complete filling of all gaps by newly formed bone could not be
      observed around either surface. In proximity to the surface, implant surface
      coating by collagen/CS positively influenced bone formation.

PMID- 24283499
TI  - Microbeads: a novel multiparticulate drug delivery technology for increasing the
      solubility and dissolution of celecoxib.
AB  - The purpose of this study was to develop a novel multipaticulate drug delivery
      technology suitable for the delivery of pre-solubilized celecoxib to the
      gastrointestinal tract and more specifically to the colon. The solubility of
      celecoxib in a range of oils, surfactants and co-solvents was evaluated.
      Celecoxib was solubilized in mixtures of these vehicles to produce liquid
      formulations. The in vitro dissolution of these liquid formulations was assessed
      and the data obtained was used to design microbead formulations containing
      celecoxib dissolved within an emulsion/micellar solution core. Microbead
      formulations were optimized to increase drug loading, avoid precipitation and to
      achieve good in vitro dissolution performance. An optimized formulation with a
      celecoxib loading of 6% w/w was produced and yielded an in vitro dissolution
      result of 80% over 6 h. The structure of these microbead formulations was
      characterized using light microscopy to reveal a correlation between droplet size
      and dissolution performance.

PMID- 24283501
TI  - Diversity of microstructural phenomena in superconducting and non-superconducting
      Rb(x)Fe(2-y)Se2: a transmission electron microscopy study at the atomic scale.
AB  - Superconducting (SC) and non-superconducting (non-SC)Rb(x)Fe(2-y)Se2 crystals
      were grown using the "self-flux" technique in order to assign the microstructural
      changes to the onset of superconductivity in complex iron selenides. The crystals
      were thoroughly characterized by magnetic susceptibility and transport
      measurements as well as powder X-ray diffraction. Special attention was paid to
      the comparison of the microstructure of the crystals with and without the
      superconducting transition by means of transmission electron microscopy (TEM). It
      is shown that the alternation of ordered and disordered regions on the sample
      surface and along the c-axis is characteristic for both SC and non-SC materials
      and therefore does not necessarily represent a trigger of superconductivity.
      Three types of electron diffraction patterns were found for the superconducting
      Rb(x)Fe(2-y)Se2 sample, of which one is observed for the first time and
      originates from alkali metal ordering. Moreover, for the superconducting
      Rb(x)Fe(2-y)Se2 material a monoclinic distortion with beta ~ 87 degrees  was
      observed, leading to the space group I2/m. This monoclinic distortion seems to be
      an attribute of the superconducting material only, whereas in the non
      superconducting sample the orthogonality of the crystallographic axes is
      preserved.

PMID- 24283500
TI  - CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese
      population.
AB  - BACKGROUND: Coronary atherosclerosis, the most common form of coronary artery
      disease (CAD), is characterized by accumulation of lipid in the walls of coronary
      arteries. Recent data from clinical trials have showed that high-density
      lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and
      development of coronary atherosclerosis. Cholesteryl ester transfer protein
      (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in
      the CETP gene were found to be associated with HDL-C levels. The aim of the
      present study is to evaluate the association of HDL-C-related CETP polymorphisms
      and risk of coronary atherosclerosis. METHODS: We investigated the association of
      seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882,
      rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of
      coronary atherosclerosis and levels of HDL-C in a case-control study in China.
      Included in the study were 420 patients with coronary atherosclerosis and 424
      healthy controls. SNP genotyping was performed by TaqMan allelic discrimination
      assay and serum lipid levels were measured by standard laboratory methods.
      RESULTS: Carriers of the AA and GA + AA genotypes of rs708272 had significant
      lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003;
      OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG
      genotype. These relations remained significant after adjustment for confounding
      effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism
      was significantly associated with serum levels of HDL-C in healthy controls (p =
      0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775
      in this study. CONCLUSIONS: Our findings indicated that CETP rs708272 may be
      associated with the risk of coronary atherosclerosis and rs1800775 may influence
      serum HDL-C levels in healthy controls in Chinese.

PMID- 24283502
TI  - Chemical kinetics and mechanisms of complex systems: a perspective on recent
      theoretical advances.
AB  - This Perspective presents a personal overview of the current status of the theory
      of chemical kinetics and mechanisms for complex processes. We attempt to assess
      the status of the field for reactions in the gas phase, at gas-solid interfaces,
      in liquid solutions, in enzymes, and for protein folding. Some unifying concepts
      such as potential energy surfaces, free energy, master equations, and reaction
      coordinates occur in more than one area. We hope this Perspective will be useful
      for highlighting recent advances and for identifying important areas for future
      research. 

PMID- 24283498
TI  - Synthetic methods for the preparation of platinum anticancer complexes.

PMID- 24283503
TI  - Hydrocarbon-related microbial processes in the deep sediments of the Eastern
      Mediterranean Levantine Basin.
AB  - During the 2011 exploration season of the EV Nautilus in the Mediterranean Sea,
      we conducted a multidisciplinary study, aimed at exploring the microbial
      populations below the sediment-water interface (SWI) in the hydrocarbon-rich
      environments of the Levantine basin. Two c. 1000-m-deep locations were sampled:
      sediments fueled by methane seepage at the toe of the Palmachim disturbance and a
      patch of euxinic sediment with high sulfide and methane content offshore Acre,
      enriched by hydrocarbon from an unknown source. We describe the composition of
      the microbial population in the top 5 cm of the sediment with 1 cm resolution,
      accompanied by measurements of methane and sulfate concentrations, and the
      isotopic composition of this methane and sulfate (delta13C(CH4), delta18O(SO4),
      and delta34S(SO4)). Our geochemical and microbiological results indicate the
      presence of the anaerobic methane oxidation (AOM) coupled to bacterial sulfate
      reduction (BSR). We show that complex methane and sulfur metabolizing microbial
      populations are present in both locations, although their community structure and
      metabolic preferences differ due to potential variation in the hydrocarbon
      source.

PMID- 24283504
TI  - Acquired aquagenic syringeal acrokeratoderma: A case series of 10 patients.
AB  - Aquagenic syringeal acrokeratoderma is a rare acquired disorder that
      predominantly affects young women. It is most commonly localised on the palms. It
      is characterised by translucent papules, oedematous plaques and keratoderma
      developing after brief exposure to water and resolving shortly after drying. We
      have observed 10 patients with this disorder within 13 months. We think that
      aquagenic syringeal acrokeratoderma is a more common condition than was
      originally anticipated as one can easily underdiagnose this entity due to the
      transient nature of its clinical findings. 

PMID- 24283505
TI  - Motor excitability during movement preparation in Tourette syndrome.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the
      occurrence of motor and vocal tics. TS has been linked to the impaired operation
      of cortical-striatal-thalamic-cortical circuits that give rise to hyper
      excitability of cortical motor areas, which may be exacerbated by dysfunctional
      intra-cortical inhibitory mechanisms. That said, many individuals gain control
      over their tics during adolescence and it has been suggested that this increased
      control arises as a result of the development of mechanisms that operate to
      suppress corticospinal excitability (CSE) ahead of volitional movements. Here we
      used single-pulse transcranial magnetic stimulation (TMS) in conjunction with a
      manual Go/NoGo task to investigate alterations in CSE ahead of volitional
      movements in a group of adolescents with TS (N = 10). Our study demonstrated that
      CSE, as measured by TMS-induced motor-evoked potentials (MEPs), was significantly
      reduced in the TS group in the period immediately preceding a finger movement.
      More specifically, we show that individuals with TS, unlike their age-matched
      controls, do not exhibit the predicted increase in mean MEP amplitude and
      decrease in MEP variability that immediately precede the execution of volitional
      movements in typically developing young adults. Finally, we report that the
      magnitude of the rise in MEP amplitude across the movement preparation period in
      TS is significantly negatively correlated with clinical measures of motor tic
      severity, suggesting that individuals with severe motor tics are least able to
      modulate motor cortical excitability.

PMID- 24283506
TI  - Role for immune monitoring to tailor induction prophylaxis in pediatric heart
      recipients.
AB  - rATG is used for HTx induction but is costly and associated with infection and
      PTLD. HYPOTHESIS: Tailoring rATG induction with CD3 monitoring results in less
      infection, reduced costs, and similar rejection. Retrospective review of HTx
      recipients receiving rATG induction. Control cases received "usual" rATG dosing
      (1.5 mg/kg/day typically * 5 days). Starting in October 2009, absolute CD3
      monitoring (target <25 cells/mm(3) ) guided rATG dosing (study cases). Outcomes
      included first-year incidence of infection/rejection, direct costs of therapy,
      and incidence of PTLD/death. Study cases (n = 32) received fewer doses of rATG
      (median 4 vs. 5, p < 0.001) and less total rATG (median 3.2 vs. 7.4 mg/kg, p <
      0.001) compared with controls (n = 17). There was no difference in incidence of
      infection, rejection, or patient survival during the first year post-HTx. There
      was one early death in both groups and one late case of PTLD in the control
      group. Drug savings were significant (median drug cost per patient $2718 vs.
      $4756, p < 0.001). CD3-tailored rATG induction in HTx recipients is associated
      with reduced drug costs and similar rates of rejection/infection. Longer follow
      up will determine whether extended benefits are associated with this induction
      monitoring strategy.

PMID- 24283507
TI  - How do children with amelogenesis imperfecta feel about their teeth?
AB  - BACKGROUND: Amelogenesis imperfecta (AI) is an inherited dental condition
      affecting enamel, which can result in significant tooth discolouration and enamel
      breakdown, requiring lifelong dental care. The possible impact of this condition
      on children and adolescents from their perspectives is not fully understood.
      AIMS: The aim of the study was to explore the impact of AI on children and
      adolescents through in-depth interviewing. The information derived from this was
      then used to construct a questionnaire to distribute to a larger cohort of AI
      patients. DESIGN: This research involved semistructured in-depth interviews with
      seven AI patients, and common themes and concepts were then identified using
      framework analysis. A questionnaire was developed based on the themes and
      subthemes identified, and completed by 40 AI patients at various stages of
      treatment. RESULTS: Children and adolescents with AI exhibited concerns regarding
      aesthetics and function. Patients also expressed a high level of concern
      regarding comments by other people and self-consciousness associated with this. A
      small number of AI patients highlighted the effect of their dental treatment and
      health on their personal life. CONCLUSION: The results indicate that there are
      marked impacts on children and adolescents as a result of AI, including
      aesthetics, function, and psychosocial.

PMID- 24283509
TI  - Measurement of skin thickness and skin elasticity to evaluate the effectiveness
      of intensive decongestive treatment in patients with lymphoedema: a prospective
      study.
AB  - BACKGROUND: Complex decongestive physiotherapy (CDP) is used to treat patients
      with severe lymphoedema. The efficacy of CDP is usually quantified by calculating
      limb volume from repeated measurements of circumference at least 10 points before
      and after treatment of an affected limb. Measurement is time-consuming and
      operator-dependent. OBJECTIVES: To determine whether decreased dermal thickness
      is correlated with decreased volume after intensive CDP. METHODS: A consecutive
      series of patients admitted for intensive CDP were studied over a 6-month period.
      Before and after CDP, we measured circumference, dermal thickness elasticity and
      finally improvement in quality of life using a visual analogue scale (VAS).
      RESULTS: Thirty patients were included in the study. Only three patients were
      previously untreated. The average relative reduction in limb volume was 4% and
      the reduction in the dermal thickness was 15% (correlation: r = 0.37, P = 0.05).
      Viscoelasticity was decreased by 13%. VAS quality of life score was improved by
      30%. CONCLUSION: Changes in dermal thickness are slightly correlated with volume
      changes before and after 5-day intensive CDP in a selected series of patients
      previously treated at home.

PMID- 24283510
TI  - Zn ion post-implantation-driven synthesis of CuZn alloy nanoparticles in Cu
      preimplanted silica and their thermal evolution.
AB  - Cu nanoparticles (NPs) were fabricated in silica by 45 keV Cu ion implantation at
      a fluence of 1.0 * 10(17) cm(-2) and were then subjected to implantation of 50
      keV Zn ions at fluences of 1.0 * 10(16), 5.0 * 10(16), and 10.0 * 10(16) cm(-2),
      respectively. Our results clearly show that post Zn ion implantation could
      significantly modify structures and components of the preformed Cu NPs and thus
      the corresponding surface plasmon resonance (SPR) absorption can be modulated in
      a wide range. In particular, CuZn alloy NPs with unique SPR absorption were
      synthesized in Cu-implanted silica followed by Zn ion implantation at a fluence
      of 5.0 * 10(16) cm(-2). During subsequent annealing, two distinguished processes
      concerning CuZn alloy NPs (i.e., realloying and dealloying) were found that
      directly result from thermally driven diffusion of Zn atoms. Moreover, owing to
      Zn diffusion, lots of core-shell nanostructures consisting of Zn-related compound
      shells around Cu cores were observed after annealing at 500  degrees C and
      higher. The underlying mechanism concerning the formation and decomposition of
      CuZn alloy NPs is discussed and presented. 

PMID- 24283508
TI  - Solubilization of therapeutic agents in micellar nanomedicines.
AB  - We use atomistic molecular dynamics simulations to reveal the binding mechanisms
      of therapeutic agents in PEG-ylated micellar nanocarriers (SSM). In our
      experiments, SSM in buffer solutions can solubilize either ~11 small bexarotene
      molecules or ~6 (2 in low ionic strength buffer) human vasoactive intestinal
      peptide (VIP) molecules. Free energy calculations reveal that molecules of the
      poorly water-soluble drug bexarotene can reside at the micellar ionic interface
      of the PEG corona, with their polar ends pointing out. Alternatively, they can
      reside in the alkane core center, where several bexarotene molecules can self
      stabilize by forming a cluster held together by a network of hydrogen bonds. We
      also show that highly charged molecules, such as VIP, can be stabilized at the
      SSM ionic interface by Coulombic coupling between their positively charged
      residues and the negatively charged phosphate headgroups of the lipids. The
      obtained results illustrate that atomistic simulations can reveal drug
      solubilization character in nanocarriers and be used in efficient optimization of
      novel nanomedicines. 

PMID- 24283511
TI  - Medium- and Long-Term Complications in Full-Arch Rehabilitations Supported by
      Upright and Tilted Implants.
AB  - PURPOSE: The purpose of this retrospective investigation was to present the
      incidence of biological and technical complications in patients treated with
      implant-supported, immediately loaded full-arch restorations. MATERIALS AND
      METHODS: Clinical data of all patients treated with full-arch, immediately loaded
      rehabilitations supported by a combination of upright and tilted implants were
      screened. Data on both technical and biological complications (such as peri
      implant mucositis and peri-implantitis) and their onset and frequency of
      occurrence were recorded and analyzed. RESULTS: The clinical records of 86
      patients (95 prosthetic rehabilitations) were included in this study. There were
      61 mandibular rehabilitations and 34 maxillary ones, all of them immediately
      loaded within 8 to 48 hours of the surgical intervention. The follow-up time
      varied from 16.3 to 112 months of function (mean 65.36 months). The most common
      biological complications were hygiene-related (n = 81; 30.2% of patients
      displayed peri-implant mucositis and 10.4% peri-implantitis). Among all
      prosthetic complications, the detachment of an element of the definitive
      prosthesis was the most frequent event (n = 20; 23.2% of patients). The total
      number of prosthetic complications was 42. Most complications were reversible and
      did not affect the overall implant/prosthesis survival rate. CONCLUSIONS: The
      occurrence in well-maintained patients of technical and biological complications
      in full-arch rehabilitations supported by a combination of tilted and upright
      implants in the medium to long term is lower than previously reported by the
      pertinent literature. Further studies are needed to confirm this result.

PMID- 24283512
TI  - ABA control of plant macroelement membrane transport systems in response to water
      deficit and high salinity.
AB  - Plant growth and productivity are adversely affected by various abiotic stressors
      and plants develop a wide range of adaptive mechanisms to cope with these adverse
      conditions, including adjustment of growth and development brought about by
      changes in stomatal activity. Membrane ion transport systems are involved in the
      maintenance of cellular homeostasis during exposure to stress and ion transport
      activity is regulated by phosphorylation/dephosphorylation networks that respond
      to stress conditions. The phytohormone abscisic acid (ABA), which is produced
      rapidly in response to drought and salinity stress, plays a critical role in the
      regulation of stress responses and induces a series of signaling cascades. ABA
      signaling involves an ABA receptor complex, consisting of an ABA receptor family,
      phosphatases and kinases: these proteins play a central role in regulating a
      variety of diverse responses to drought stress, including the activities of
      membrane-localized factors, such as ion transporters. In this review, recent
      research on signal transduction networks that regulate the function ofmembrane
      transport systems in response to stress, especially water deficit and high
      salinity, is summarized and discussed. The signal transduction networks covered
      in this review have central roles in mitigating the effect of stress by
      maintaining plant homeostasis through the control of membrane transport systems.

PMID- 24283513
TI  - Surface plasmon engineering in graphene functionalized with organic molecules: a
      multiscale theoretical investigation.
AB  - Graphene was recently shown to support deep subwavelength surface plasmons at
      terahertz frequencies characterized by low energy loss and strong field
      localization, both highly desirable. The properties of graphene can be locally
      tuned by applying an external gate voltage or by the adsorption of organic
      molecules that lead to doping through charge transfer. Local tuning of the
      electronic features of graphene opens the possibility to realize any desired
      gradient index profile and thus brings large flexibility to control and
      manipulate the propagation of surface plasmons. Here, we explore this possibility
      created by functionalizing graphene with organic molecules. We employ a
      multiscale theoretical approach that combines first-principles electronic
      structure calculations and finite-difference time-domain simulations coupled by
      surface conductivity. We show that by patterning two types of organic molecules
      on graphene, a plasmonic metasurface can be realized with any gradient effective
      refractive index profile to manipulate surface plasmon beams as desired. The
      special properties of such devices based on functionalized graphene are compared
      to the similar metamaterials based on metallic films on top of a gradient index
      dielectric substrate. Using this idea, we design and analyze an ultrathin
      broadband THz plasmonic lens as proof-of-concept, while more sophisticated index
      profiles can also be realized and various plasmonic applications are readily
      accessible. 

PMID- 24283514
TI  - beta-lactam allergy: clinical implications and costs.
AB  - BACKGROUND: beta-lactam allergy is the most commonly reported medication allergy
      and it remains a key issue in antibiotic prescribing. A detailed and accurate
      history taking play a key role in preventing potentially serious clinical
      incidents and it may contribute in reducing costs. METHODS: Data were collected
      for patients with a documented penicillin allergy on their drug chart during a
      six month period. Sources included the inpatient drug charts and medical notes.
      Adherence to hospital guidelines was audited and costs of treatments were
      calculated. RESULTS: 94 patients with a history of penicillin allergy were
      included. Compliance with the hospital antibiotic policy was 81% and 52% of cases
      had a description of the reaction documented. The mean additional cost per
      patient was L89.29 (excluding VAT). CONCLUSIONS: It is important to maintain a
      high level of vigilance and constantly educate all healthcare professionals
      involved in prescribing and dispensing antibiotics in order to avoid the
      unnecessary use of non-penicillin-based antibiotics and associated cost
      implication.

PMID- 24283515
TI  - First outbreak of West Nile virus neuroinvasive disease in humans, Croatia, 2012.
AB  - Between September 6 and 21, 2012, seven human cases of West Nile virus (WNV)
      neuroinvasive infection were laboratory confirmed in Croatia. The median patient
      age was 62 years (range 48-77). Five patients presented with meningoencephalitis
      and two patients with meningoencephalitis followed by acute flaccid paralysis.
      Four of them had an underlying disease (hypertension). Using enzyme-linked
      immunosorbent assay (ELISA), WNV-specific immunoglobulin M (IgM) and IgG
      antibodies of low avidity were detected in six patients, whereas one showed only
      IgM antibodies. All samples were confirmed using plaque-reduction neutralization
      and microneutralization tests. Five patients recovered fully. Before human cases
      were reported, acute asymptomatic WNV infection was demonstrated by detection of
      IgM antibodies in sentinel horses. Moreover, an increased WNV IgG seropositivity
      in horses was detected in counties where human cases occurred. Adulticidal and
      larvicidal treatments were administered immediately in the respective places of
      residence. The end of the warm season contributed to the fact that there were no
      new cases of WNV disease recorded.

PMID- 24283516
TI  - Ba4Ta2O9 oxide prepared from an oxalate-based molecular precursor
      characterization and properties.
AB  - A novel heterometallic oxalate-based compound, {Ba2(H2O)5[TaO(C2O4)3]HC2O4}.H2O
      (1), was obtained by using an (oxalato)tantalate(V) aqueous solution as a source
      of the complex anion and characterized by X-ray single-crystal diffraction, IR
      spectroscopy, and thermal analysis. Compound 1 is a three-dimensional (3D)
      coordination polymer with the Ta atom connected to eight neighboring Ba atoms
      through the oxalate ligands and the oxo oxygen group. Thermal treatment of 1 up
      to 1200  degrees C leads to molecular precursor-to-material conversion that
      yields the mixed-metal gamma-Ba4Ta2O9 phase. This high-temperature gamma-Ba4Ta2O9
      polymorph has the 6H-perovskite structure (space group P6(3)/m), in which the
      Ta2O9 face-sharing octahedral dimers are interconnected via corners to the
      regular BaO6 octahedra. To date, gamma-Ba4Ta2O9 has never been obtained at room
      temperature, because of the reduction of symmetry (P6(3)/m -> P2(1)/c) that
      usually occurs during the cooling. Spectroscopic, optical, photocatalytic, and
      electrical properties of the obtained gamma-Ba4Ta2O9 phase were investigated. In
      addition to the experimental data, an absorption spectrum and band structure of
      the gamma-Ba4Ta2O9 polymorph were calculated using density functional theory.

PMID- 24283518
TI  - Renal cryoablation versus robot-assisted partial nephrectomy: Washington
      University long-term experience.
AB  - BACKGROUND AND PURPOSE: American Urological Association guidelines endorse
      partial nephrectomy as the preferred treatment for patients with small renal
      masses, while considering patients with significant comorbidities potential
      candidates for ablative therapy. We compared perioperative, renal functional, and
      oncologic outcomes of renal cryoablation and robot-assisted partial nephrectomy
      (RAPN) based on our long-term institutional experience. PATIENTS AND METHODS: A
      retrospective review evaluated 267 patients who underwent laparoscopic or
      percutaneous cryoablation (July 2000-June 2011) and 233 patients who underwent
      RAPN (June 2007-September 2012) for enhancing renal masses at Washington
      University. RESULTS: The perioperative complication rate was 8.6% in the
      cryoablation group vs 9.4% in the RAPN group (P = 0.75). There was no significant
      difference in complication risk between the two treatment modalities on
      multivariate analysis. Estimated glomerular filtration rate (eGFR) at last follow
      up was 6% lower than preoperative eGFR in the cryoablation group and 13% lower in
      the RAPN group (P<0.01). The advantage of cryoablation in preserving renal
      function persisted on multivariate analysis (P = 0.02). In patients with
      pathologically proven renal-cell carcinoma, 5-year Kaplan-Meier disease-free
      survival (DFS), cancer-specific survival (CSS), and overall survival was 83.1%,
      96.4%, and 77.1% in the cryoablation cohort vs 100%, 100%, and 91.7% in the RAPN
      group. Mean time to recurrence was 16.2 months (range 0.03-42.0 mos).
      Cryoablation was associated with increased recurrence risk (hazard ratio [HR] =
      11.4, P = 0.01) on multivariate analysis. CONCLUSIONS: Cryoablation and RAPN are
      safe alternatives for managing renal masses amenable to nephron-sparing
      interventions, offering acceptable morbidity and excellent renal preservation.
      While RAPN offers improved DFS, for those willing to undergo close postoperative
      monitoring and accept the potential need for re-treatment of recurrent disease,
      cryoablation offers excellent long-term CSS.

PMID- 24283519
TI  - Progress in the medical treatment of epilepsy: an overview of new antiepileptic
      drugs.

PMID- 24283517
TI  - Evidence that TNF-beta (lymphotoxin alpha) can activate the inflammatory
      environment in human chondrocytes.
AB  - INTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint
      diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor
      necrosis factor alpha (TNF-alpha) as this has proven benefits. However, a large
      number of patients do not respond to or become resistant to anti-TNF-alpha
      therapy. While the role of TNF-alpha in RA is quite evident, the role of TNF
      beta, also called lymphotoxin-alpha (LT-alpha), is unclear. In this study we
      investigated whether TNF-beta and its receptor play a role in chondrocytes in the
      inflammatory environment. METHODS: An in vitro model of primary human
      chondrocytes was used to study TNF-beta-mediated inflammatory signaling. RESULTS:
      Cytokine-induced inflammation enhances TNF-beta and TNF-beta-receptor expression
      in primary human chondrocytes accompanied by the up-regulation of inflammatory
      (cyclooxygenase-2), matrix degrading(matrix metalloproteinase-9 and -13) and
      apoptotic (p53, cleaved caspase-3) signaling pathways, all known to be regulated
      by NF-kappaB. In contrast, anti-TNF-beta, similar to the natural NF-kappaB
      inhibitor (curcumin, diferuloylmethane) or the knockdown of NF-kappaB by using
      antisense oligonucleotides (ASO), suppressed IL-1beta-induced NF-kappaB
      activation and its translocation to the nucleus, and abolished the pro
      inflammatory and apoptotic effects of IL-1beta. This highlights,at least in part,
      the crucial role of NF-kappaB in TNF-beta-induced-inflammation in cartilage,
      similar to that expected for TNF-alpha. Finally, the adhesiveness between TNF
      beta-expressing T-lymphocytes and the responding chondrocytes was significantly
      enhanced through a TNF-beta-induced inflammatory microenvironment. CONCLUSIONS:
      These results suggest for the first time that TNF-beta is involved in
      microenvironment inflammation in chondrocytes during RA parallel to TNF-alpha,
      resulting in the up-regulation of NF-kappaB signaling and activation of pro
      inflammatory activity.

PMID- 24283520
TI  - Treatment of acute stroke.

PMID- 24283521
TI  - European Cooperative Acute Stroke Study (ECASS): (rt-PA-Thrombolysis in acute
      stroke) study design and progress report.
AB  - At present, no therapy for acute ischemic stroke has been established. Vascular
      occlusions are demonstrated in up to 75-90% of ischemic stroke patients, and it
      is assumed that rapid lysis of the causal vascular occlusion will improve outcome
      of ischemic stroke. The purpose of the ECASS study is to evaluate whether
      thrombolytic therapy with recombinant tissue plasminogen activator, alteplase,
      improves outcome compared to a placebo-treated control group. Patients with acute
      ischemic hemispheric stroke in whom intravenous rt-PA (alteplase) could be
      initiated within 6 h from the onset of symptoms were evaluated by neurological
      examination and cerebral computed tomographic scans (CT scans) of the brain.
      Patients fulfilling inclusion criteria and not meeting any exclusion criteria
      were, after informed consent, treated by 1.1 mg rt-PA per kg body weight (max 100
      mg) intravenously or placebo. No angiographic evaluation was included in the
      trial. In total, 623 patients were randomized in 14 European countries. In
      addition, 81 patients were treated in an open pilot phase with the active drug.
      Treatment effect was evaluated using the Barthel Index and the Modified Rankin
      Scale at 90 +/- 7 days in both an intention-to-treat analysis and an explanatory
      analysis. The clinical course was evaluated by repeated neurological ratings on
      the Scandinavian Stroke Scale. Adverse events (intracranial hemorrhage or
      cerebral edema) were evaluated by repeating CT scans at 24 h and at 7 days.
      Recruitment was terminated in March 1994. Follow-up evaluations were terminated
      in late June 1994. The first unblinded results are expected in February 1995.
      Overall mortality was 18.5% in the pilot study and 18.9% in the randomized trial.
      The incidence of cerebral bleeding complications associated with clinical
      deterioration was 11.1% (pilot) and 6.5% (randomized trial). 

PMID- 24283522
TI  - Does frontal cortex hypometabolism in progressive supranuclear palsy result from
      subcortical dysfunction?
AB  - Progressive supranuclear palsy (PSP), a neurodegenerative disease with frontal
      lobe-like features, shows brain hypometabolism which predominates in frontal
      cortex, although the most severe histopathological lesions are subcortical. To
      test the hypothesis of the subcortical origin of the metabolic dysfunction in
      frontal cortex, we used previously obtained data measured using positron emission
      tomography (PET) in PSP patients and controls to examine the metabolic links
      between cortical and subcortical brain regions. We calculated interregional
      correlations of metabolic values in PSP patients and we compared these values to
      those obtained in controls. Compared to 20 age-matched controls, the 20 PSP
      patients studied showed an increase in positive metabolic coupling between
      frontal and non-frontal cortical regions. There was an abnormal linkage between
      frontal cortex and thalamus hypometabolism, the latter partly coupled to caudate
      nucleus hypometabolism. This study suggests a subcortical origin for frontal
      cortex hypometabolism in which thalamic activity appears to play a pivotal role. 

PMID- 24283523
TI  - Cerebral amyloid angiopathy, leukoencephalopathy and dementia of acute onset.
      Clinicopathological study of a new case.
AB  - Cerebral amyloid angiopathy (CAA) is a well-established cause of brain hemorrhage
      in the elderly. The association of CAA with other structural brain lesions is
      less well known. We report a 69 year old diabetic woman with dementia of acute
      onset Cranial CT and MRI showed diffuse leukoencephalopathy with predominant
      right parieto-occipital distribution. Pathological study demonstrated severe CAA.
      We review the association of CAA with dementia and leukoencephalopathy. 

PMID- 24283524
TI  - Central motor conduction as a measure of disease progression in early multiple
      sclerosis.
AB  - We monitored disease progression in 27 patients with clinically or laboratory
      supported definite multiple sclerosis by means of clinical assessments [expanded
      disability status scale (EDSS), and the neurologic rating scale (NRS)] repeated
      at 6 month intervals for 2 years. Each clinical assessment was accompanied by
      evoked potentials (EP; visual, brain stem auditory, and somatosensory evoked
      potentials), motor evoked potentials elicited by magnetic stimulation, and
      magnetic resonance imaging of the brain and brain stem. Central conduction
      indices were calculated for each central pathway. According to the EDSS 18
      patients deteriorated, eight were unchanged and one improved. The central motor
      conduction index (CMCI) was the only conduction parameter which correlated
      significantly with both EDSS and NRS at baseline [rho=0.51 (EDSS); -0.65 (NRS)],
      at final investigation, and when individual changes from baseline to final
      investigation were addressed (rho=0.38; -0.38). Individual deteriorations or
      improvements of the CMCI during the 2 years correlated with changes in both EDSS
      and NRS (rho = 0.51; -0.38). The MRI parameters did not correlate with the
      clinical scores. The concordance between MRI and CMCI in detection of disease
      activity was 63%. We conclude that the CMCI stands out as an objective, accurate
      and easily obtained outcome parameter. 

PMID- 24283525
TI  - Muscle activity changes in spasmodic torticollis after botulinum toxin treatment.
AB  - We assessed electromyographic (EMG) activity in neck muscles before and after
      botulinum toxin injections in 28 patients with spasmodic torticollis (ST) to
      investigate possible changes in muscle activation after treatment. A six-channel
      EMG with surface electrodes was used to record activity of sternocleiodomastoid,
      trapezius and splenius capitis bilaterally. Objective benefit (>25% reduction in
      Tsui's score) occurred in 22 patients (78%). Of the 168 muscles studied before
      botulinum toxin injections, 90 presented EMG activity. Sixty-eight of these
      muscles were injected and a decrease in EMG activity occurred in 44 (65%) of
      them. A decrease in EMG activity was also detected in 15 (68%) of those which
      were not injected. On the other hand, 70 of the 78 muscles without pre-botulinum
      toxin EMG activity were not injected. However, after treatment, EMG activity
      increased in 37 (52%) of these muscles. These changes involved 18 patients and
      occurred without concomitant change in the main direction of head deviation
      despite the improvement observed in most cases. These results suggest that in ST
      head turning results from an abnormal central motor program which results in non
      specific neck muscle activation. 

PMID- 24283526
TI  - The premorbid personality of patients with Parkinson's disease: evidence with the
      Tridimensional Personality Questionnaire.
AB  - The premorbid personality traits of 102 patients with Parkinson's disease (PD)
      and 57 age-matched healthy controls were studied by the recently developed
      Tridimensional Personality Questionnaire. We found significantly fewer (p < 0.05)
      of a group of traits called "novelty seeking" (NS), but no changes in "harm
      avoidance" (HA) and "reward dependence" (RD), in PD patients, for the period
      approximately 5-10 years before the onset of the disease, compared to controls.
      Individuals who are lower than average in NS and average in HA and RD are
      described as reflective, rigid, loyal, stoic, slow-tempered, frugal, orderly, and
      persistent Since NS is thought to be directly related to central dopaminergic
      reactivity, the premorbid expression of these behaviors may be the reflection of
      neurochemical deficits (hypodopaminergic tone) accompanying the presymptomatic
      phase of PD. 

PMID- 24283527
TI  - Clinical intra- and interfamilial variability of cluster headache.
AB  - Our recent description of a 17- and 2-fold increased risk of cluster headache
      among first- and second-degree relatives, respectively, strongly suggests that
      cluster headache has a genetic cause. Eighteen families with familial occurrence
      of cluster headache according to the criteria of the International Headache
      Society were included. Clinical intra- and interfamilial variability of cluster
      headaches was analyzed in 44 cases (31 males and 13 females) from 18 families.
      None of the families showed a distinctive pattern of symptoms except for the two
      families with chronic cluster headache. Their affected male relatives had a high
      number (1-8) of attacks per day in their cluster periods. Children had a
      significantly lower age at onset than parents (p = 0.018), but it is uncertain
      whether this is a real phenomenon or caused by memory bias. However, the possible
      existence of anticipation is important in the search for the gene. Co-occurrence
      of migraine with and without aura was not increased in familial cases of cluster
      headache compared with the prevalence of migraine with and without aura in the
      Danish population, implying different etiologies. Our results suggest that
      episodic, chronic and chronic cluster headaches evolved from episodic have a
      common etiology and genetic heterogeneity is unlikely on clinical grounds. 

PMID- 24283528
TI  - Cervical dystonia. Prognostic factors for long-term botulinum toxin response.

PMID- 24283529
TI  - Mianserin, a 5-HT2 receptor antagonist, in the treatment of delirium: an open
      study.
AB  - To determine the role of the serotonin system at the 5-HT2 receptors on delirium
      in the aged, we assessed the effects of mianserin, a relatively selective 5-HT2
      receptor antagonist, in such patients. Twenty-six delirious patients [four
      without dementia, nine with Alzheimer's disease (AD), 13 with ischemic vascular
      dementia (IVD)] were included in the open study. After the dose titration period,
      the mean dose of mianserin administrated was 31.2 mg in delirious patients
      without dementia, 25.0 mg in delirious patient with AD and 25.9 mg in delirious
      patients with IVD. The average total score of each patient group on a symptom
      rating scale was reduced significantly within 24 h (p < 0.05). A complete
      elimination of symptoms was noted in all four delirious patients without
      dementia. In the nine delirious patients with AD, marked improvement was noted in
      four patients (44.4%), moderate improvement in four (44.4%) and no improvement in
      one (11.1%). In the 13 delirious patients with IVD marked improvement was noted
      in seven (53.8%), moderate improvement in five (38.5%) and no improvement in one
      (7.7%). The rapidity of the improvement may be attributable to mianserin's
      antagonism at the 5-HT2 receptors, and such serotonin antagonism at the 5-HT2
      receptors may be important in treating delirium.- 

PMID- 24283530
TI  - Opportunities for teaching and research in clinical neurosciences in Central and
      Eastern Europe.

PMID- 24283531
TI  - The impact of economic change on clinical neurology and research: a window into
      the European situation(1.).

PMID- 24283533
TI  - Xq28 (MECP2) microdeletions are common in mutation-negative females with Rett
      syndrome and cause mild subtypes of the disease.
AB  - BACKGROUND: Rett syndrome (RTT) is an X-linked neurodevelopmental disease
      affecting predominantly females caused by MECP2 mutations. Although RTT is
      classically considered a monogenic disease, a stable proportion of patients, who
      do not exhibit MECP2 sequence variations, does exist. Here, we have attempted at
      uncovering genetic causes underlying the disorder in mutation-negative cases by
      whole genome analysis using array comparative genomic hybridization (CGH) and a
      bioinformatic approach. RESULTS: Using BAC and oligonucleotide array CGH, 39
      patients from RTT Russian cohort (in total, 354 RTT patients), who did not bear
      intragenic MECP2 mutations, were studied. Among the individuals studied, 12
      patients were those with classic RTT and 27 were those with atypical RTT. We have
      detected five 99.4 kb deletions in chromosome Xq28 affecting MECP2 associated
      with mild manifestations of classic RTT and five deletions encompassing MECP2
      spanning 502.428 kb (three cases), 539.545 kb (one case) and 877.444 kb (one
      case) associated with mild atypical RTT. A case has demonstrated somatic
      mosaicism. Regardless of RTT type and deletion size, all the cases exhibited mild
      phenotypes. CONCLUSIONS: Our data indicate for the first time that no fewer than
      25% of RTT cases without detectable MECP2 mutations are caused by Xq28
      microdeletions. Furthermore, Xq28 (MECP2) deletions are likely to cause mild
      subtypes of the disease, which can manifest as both classical and atypical RTT.

PMID- 24283534
TI  - Effective application of multiple locus variable number of tandem repeats
      analysis to tracing Staphylococcus aureus in food-processing environment.
AB  - A total of 256 isolates of Staphylococcus aureus were isolated from 98 samples
      (34 swabs and 64 food samples) obtained from small or medium meat- and cheese
      processing plants in Slovakia. The strains were genotypically characterized by
      multiple locus variable number of tandem repeats analysis (MLVA), involving
      multiplex polymerase chain reaction (PCR) with subsequent separation of the
      amplified DNA fragments by an automated flow-through gel electrophoresis. With
      the panel of isolates, MLVA produced 31 profile types, which was a sufficient
      discrimination to facilitate the description of spatial and temporal aspects of
      contamination. Further data on MLVA discrimination were obtained by typing a
      subpanel of strains by multiple locus sequence typing (MLST). MLVA coupled to
      automated electrophoresis proved to be an effective, comparatively fast and
      inexpensive method for tracing S. aureus contamination of food-processing
      factories. SIGNIFICANCE AND IMPACT OF THE STUDY: Subspecies genotyping of
      microbial contaminants in food-processing factories may facilitate identification
      of spatial and temporal aspects of the contamination. This may help to properly
      manage the process hygiene. With S. aureus, multiple locus variable number of
      tandem repeats analysis (MLVA) proved to be an effective method for the purpose,
      being sufficiently discriminative, yet comparatively fast and inexpensive. The
      application of automated flow-through gel electrophoresis to separation of DNA
      fragments produced by multiplex PCR helped to improve the accuracy and speed of
      the method.

PMID- 24283535
TI  - Environmental harshness is positively correlated with intraspecific divergence in
      mammals and birds.
AB  - Life on Earth is conspicuously more diverse in the tropics. Although this
      intriguing geographical pattern has been linked to many biotic and abiotic
      factors, their relative importance and potential interactions are still poorly
      understood. The way in which latitudinal changes in ecological conditions
      influence evolutionary processes is particularly controversial, as there is
      evidence for both a positive and a negative latitudinal gradient in speciation
      rates. Here, we identify and address some methodological issues (how patterns are
      analysed and how latitude is quantified) that could lead to such conflicting
      results. To address these issues, we assemble a comprehensive data set of the
      environmental correlates of latitude (including climate, net primary productivity
      and habitat heterogeneity) and combine it with biological, historical and
      molecular data to explore global patterns in recent divergence events
      (subspeciation). Surprisingly, we find that the harsher conditions that typify
      temperate habitats (lower primary productivity, decreased rainfall and more
      variable and unpredictable temperatures) are positively correlated with greater
      subspecies richness in terrestrial mammals and birds. Thus, our findings indicate
      that intraspecific divergence is greater in regions with lower biodiversity, a
      pattern that is robust to both sampling variation and latitudinal biases in
      taxonomic knowledge. We discuss possible causal mechanisms for the link between
      environmental harshness and subspecies richness (faster rates of evolution,
      greater likelihood of range discontinuities and more opportunities for
      divergence) and conclude that this pattern supports recent indications that
      latitudinal gradients of diversity are maintained by simultaneously higher
      potentials for both speciation and extinction in temperate than tropical regions.

PMID- 24283536
TI  - The relationship between skin aging and steady state ultraweak photon emission as
      an indicator of skin oxidative stress in vivo.
AB  - BACKGROUND/PURPOSE: Ultraweak photon emission (UPE) is one potential method to
      evaluate the oxidative status of the skin in vivo. However, little is known about
      how the daily oxidative stress of the skin is related to skin aging-related
      alterations in vivo. We characterized the steady state UPE and performed a skin
      survey. METHODS: We evaluated the skin oxidative status by UPE, skin elasticity,
      epidermal thickness and skin color on the inner upper arm, the outer forearm, and
      the buttock of 70 Japanese volunteers. RESULTS: The steady state UPE at the three
      skin sites increased with age. Correlation analysis revealed that the steady
      state UPE only from the buttock was related to skin elasticity, which showed age
      dependent changes. Moreover, analysis by age group indicated that b* values of
      the inner upper arm of subjects in their 20s were inversely correlated with UPE
      as occurred in buttock skin. In contrast, photoaged skin did not show a clear
      relationship with steady state UPE because the accumulation of sun-exposure might
      influence the sensitivity to oxidative stress. CONCLUSION: These results suggest
      that steady state UPE reflects not only intrinsic skin aging and cutaneous color
      but also the current oxidative status independent of skin aging.

PMID- 24283537
TI  - Carbohydrate metabolism changes in Prunus persica gummosis infected with
      Lasiodiplodia theobromae.
AB  - Peach gummosis represents a significant global disease of stone fruit trees and a
      major disease in the south peach production area of the Yangtze River of China.
      In this study, the carbohydrate composition of peach shoots during infection by
      Lasiodiplodia theobromae was examined. The expression of genes related to
      metabolic enzymes was also investigated. Control wounded and noninoculated
      tissue, lesion tissue, and wounded and inoculated surrounding lesion tissue of
      peach shoots were analyzed. Soluble sugars, glucose, mannose, arabinose, and
      xylose significantly increased in inoculated tissues of peach shoots compared
      with control tissues at different times after inoculation. Accumulation of
      polysaccharides was also observed by section observation and periodic acid
      Schiff's reagent staining during infection. Analysis using quantitative reverse
      transcription polymerase chain reaction revealed that the abundance of key
      transcripts on the synthesis pathway of uridine diphosphate (UDP)-D-glucuronate,
      UDP-D-galactose, and UDP-D-arabinose increased but the synthesis of L-galactose
      and guanosine diphosphate-L-galactose were inhibited. After inoculation, the
      transcript levels of sugar transport-related genes (namely, SUT, SOT, GMT, and
      UGT) was induced. These changes in sugar content and gene expression were
      directly associated with peach gum polysaccharide formation and may be
      responsible for the symptoms of peach gummosis.

PMID- 24283538
TI  - Diversity of Ralstonia solanacearum in French Guiana expands knowledge of the
      "emerging ecotype".
AB  - Although bacterial wilt remains a major plant disease throughout South America
      and the Caribbean, the diversity of prevalent Ralstonia solanacearum populations
      is largely unknown. The genetic and phenotypic diversity of R. solanacearum
      strains in French Guiana was assessed using diagnostic polymerase chain reactions
      and sequence-based (egl and mutS) genotyping on a 239-strain collection sampled
      on the families Solanaceae and Cucurbitaceae, revealing an unexpectedly high
      diversity. Strains were distributed within phylotypes I (46.9%), IIA (26.8%), and
      IIB (26.3%), with one new endoglucanase sequence type (egl ST) found within each
      group. Phylotype IIB strains consisted mostly (97%) of strains with the emerging
      ecotype (IIB/sequevar 4NPB). Host range of IIB/4NPB strains from French Guiana
      matched the original emerging reference strain from Martinique. They were
      virulent on cucumber; virulent and highly aggressive on tomato, including the
      resistant reference Hawaii 7996; and only controlled by eggplant SM6 and Surya
      accessions. The emerging ecotype IIB/4NPB is fully established in French Guiana
      in both cultivated fields and uncultivated forest, rendering the hypothesis of
      introduction via ornamental or banana cuttings unlikely. Thus, this ecotype may
      have originated from the Amazonian region and spread throughout the Caribbean
      region.

PMID- 24283539
TI  - Fitness attributes of Fusarium graminearum isolates from wheat in New York
      possessing a 3-ADON or 15-ADON trichothecene genotype.
AB  - In all, 50 isolates of Fusarium graminearum from wheat spikes in New York,
      including 25 isolates each of the 15-acetyl-deoxynivalenol (15-ADON) and 3-ADON
      genotype, were tested to determine whether 3-ADON isolates are more fit for
      saprophytic survival and pathogenicity on wheat spikes than are 15-ADON isolates.
      The isolates were characterized and compared for 14 different attributes of
      saprophytic fitness and pathogenic fitness on a susceptible wheat variety.
      Isolates of the two genotypes could not be differentiated for most of these
      traits. Three principle components-ascospore production on corn stalks, total
      trichothecene amount in wheat kernels, and incidence of diseased spikelets up
      from the point of inoculation-accounted for 29.4, 18.9, and 10.8% of the
      variation among the isolates, respectively. A bootstrapping procedure grouped the
      isolates into two distinct groups, with 27 and 23 isolates each, with isolates
      from both genotypes represented in similar proportions (15-ADON/3-ADON, n = 14/13
      and 11/12). Within the contemporary population of F. graminearum causing wheat
      head blight in New York, isolates with a 3-ADON genotype did not possess any
      detectable advantage over isolates with a 15-ADON genotype in saprophytic fitness
      or in pathogenic fitness on a susceptible wheat cultivar.

PMID- 24283540
TI  - Effects of Meloidogyne incognita and Thielaviopsis basicola on cotton growth and
      root morphology.
AB  - Effects of the root-knot nematode Meloidogyne incognita and the fungal pathogen
      Thielaviopsis basicola on cotton seedling growth and root morphology were
      evaluated in controlled environmental experiments. Four pathogen treatments,
      including noninfested soil, soil infested with M. incognita, soil infested with
      T. basicola, and soil infested with both pathogens were evaluated at soil bulk
      densities (BDs) of 1.25 and 1.50 g/cm(3). Plant growth and the morphology of the
      root systems were evaluated 44 days after planting. Infestation with M. incognita
      and T. basicola together significantly reduced seedling emergence, number of stem
      nodes, and root system volume compared with either pathogen alone. Either M.
      incognita or T. basicola reduced plant height, root fresh weight, top dry weight;
      root parameters total root length, surface area, and links; and root topological
      parameters magnitude, altitude, and exterior path length. M. incognita infection
      increased root radius. Root colonization by T. basicola increased with the
      presence of M. incognita at the lower soil BD. In contrast to previous research
      with Pythium spp., root topological indices (TIs) were similar with all of the
      treatments. Root TIs were near 1.92, indicating a herringbone (less branching)
      root architectural structure. Studying root architecture using a topological
      model offers an additional approach to evaluating fungi and nematodes and their
      interactions for soilborne-pathogen systems.

PMID- 24283541
TI  - Applicability of dermoscopy for evaluation of patients' response to nonablative
      therapies for the treatment of superficial basal cell carcinoma.
AB  - BACKGROUND: Applicability of dermoscopy in evaluation of outcome and monitoring
      of superficial basal cell carcinoma (sBCC) after nonablative therapies has not
      been sufficiently assessed. OBJECTIVES: Certain dermoscopic criteria, namely
      pigmented structures, ulceration and arborizing vessels, have been suggested to
      predict the presence of residual disease [residual disease-associated dermoscopic
      criteria (RDADC)]. We aimed to assess this hypothesis. PATIENTS AND METHODS:
      Lesions exhibiting RDADC 3 months after treatment were biopsied and in the case
      of histopathological confirmation were excised. Lesions characterized by
      white/red structureless areas, superficial fine telangiectasias, or lacking any
      dermoscopic criterion, were monitored for 12 months. RESULTS: At the 3-month
      evaluation, one or more of the RDADC were detected in 25/98 (25.5%) sBCCs, in
      which histology confirmed tumour persistence. In 45 (61.6%) of the 73 remaining
      lesions, dermoscopy showed white/red structureless areas and/or superficial fine
      telangiectasias. Twenty-eight lacked any dermoscopic criterion of sBCC. The two
      latter groups entered follow-up. In total, disease recurred in 13 (17.8%) of the
      73 lesions. CONCLUSIONS: RDADC accurately predict residual disease. Absence of
      dermoscopic criteria of sBCC safely predicts complete histopathological
      clearance. Detection of white/red structureless areas and/or superficial fine
      telangiectasias warrants close monitoring to recognize early recurrence.

PMID- 24283542
TI  - No place is safe: sexual abuse of children in rural Bangladesh.
AB  - During July 2007 to June 2010, BRAC, a nongovernment organization in Bangladesh,
      reported 713 incidents of rape and attempted rape of children (< 18 years) in
      rural Bangladesh. This study explores these 713 incidents to identify possible
      patterns related to the victims, perpetrators, and different dynamics of the
      incidents. Rape and attempted rape, particularly of young girls, constituted 64%
      of all reported incidents of violence against children. Children were found to be
      abused by men from all walks of life, mainly by non-family-members (83%). Similar
      diversity was seen in the location, time, and context of the incidents. The
      present study attempts to put forward an overall picture of the depth of the
      problem of child sexual abuse in rural Bangladesh, linking the incidents with the
      socially constructed gender relations of power and how it perpetuates sexual
      abuse of children, especially girls. 

PMID- 24283543
TI  - Depression and parenting by nonoffending mothers of children who experienced
      sexual abuse.
AB  - Parenting may be one mechanism by which depression in nonoffending mothers
      impacts child emotional and behavioral adjustment after sexual abuse. This study
      examined the relationship between self-reported maternal depression and parenting
      behaviors by nonoffending mothers of children who experienced sexual abuse. The
      participants were 204 nonoffending biological mother-child pairs recruited from a
      clinic providing services for children who experienced sexual abuse. The mothers
      completed pretreatment self-report measures of demographic information,
      depression, and parenting behaviors. Children (7 to 17 years) completed a measure
      of mothers' parenting behaviors. Mothers with clinically high levels of self
      reported depression employed more inconsistent parenting behavior and provided
      poorer monitoring/supervision of their children than mothers without clinically
      high levels of self-reported depression. Implications for clinical practice and
      future research are discussed. 

PMID- 24283544
TI  - Exploratory evaluation of a school-based child sexual abuse prevention program.
AB  - Internationally, efficacy studies of school-based child sexual abuse prevention
      programs display a series of methodological shortcomings. Few studies include
      adolescent participants, recording of disclosures has been inconsistent, and no
      studies to date have assessed presenter adherence to program protocols or
      summated the costs of program implementation. A pretest-posttest waitlist control
      design was used to evaluate the Tweenees program delivered to grade 6 (n = 88)
      and grade 7/8 students (n = 117) compared to a control (n = 185). Outcome
      measures included a knowledge/skills questionnaire, systematic coding of
      disclosures, and video interaction analysis of lessons. Costs were calculated per
      student, class, and school. Adolescents made small knowledge and skills gains
      indicating a program ceiling effect. Implementation analysis suggests low levels
      of adult control facilitated disclosures. Program costs were relatively
      inexpensive. Recommendations are made for future research.

PMID- 24283545
TI  - Expert testimony influences juror decisions in criminal trials involving
      recovered memories of childhood sexual abuse.
AB  - We examined the impact of expert witness orientation (researcher or clinical
      practitioner) and type of testimony (testimony for the prosecution, defense, both
      prosecution and defense, or no testimony) on mock jurors' decisions in a sexual
      abuse trial. Participants acted as mock jurors on a sexual abuse criminal trial
      based on recovered memory that included expert witness testimony. Results showed
      that expert witness testimony provided by a researcher did not impact mock
      jurors' guilt ratings any differently than the expert witness testimony provided
      by a clinical practitioner. However, type of testimony had a significant effect
      on jurors' guilt ratings such that jurors who read only defense or only
      prosecution testimony made decisions favoring the relevant side. 

PMID- 24283546
TI  - Estimating age: college males versus convicted male child sex offenders.
AB  - Two samples, male college students and convicted male child sex offenders, are
      compared on their abilities to accurately estimate the age group of a series of
      photographs of a sole female ranging in age from 11 to 29. Both samples tend to
      overestimate the age group of the subject photos, and no significant difference
      was found between college students and convicted child sex offenders in their
      ability to estimate the age of females. Both groups are compared demographically,
      and only limited differences were found. The implications are discussed in regard
      to theory and prevention of child sexual abuse. 

PMID- 24283547
TI  - Internet-initiated sexual assault among U.S. adolescents reported in newspapers,
      1996-2007.
AB  - This article provides an assessment over time of the incidence of newspaper
      reported Internet-initiated sexual assaults among U.S. adolescents undergoing
      adjudication from 1996 to 2007. Of 812 newspaper reports of adjudicated Internet
      initiated sexual assault, most (79.2%) victims were female, and the median age
      was 14 years. The incidence rate of these reports increased over the 12-year
      period for females but remained steady for males. The frequency of these assaults
      was much less than reported for other types of sexual assaults in this age group.
      These estimates hopefully will assist in a greater understanding of these
      assaults, aid in interventions to decrease their occurrence, and guide effective
      policymaking that will reduce all types of sexual assault among adolescents. 

PMID- 24283549
TI  - Eczema and sensitization to common allergens in the United States: a multiethnic,
      population-based study.
AB  - The relationship between food and environmental allergens in contributing to
      eczema risk is unclear on a multiethnic population level. Our purpose was to
      determine whether sensitization to specific dietary and environmental allergens
      as measured according to higher specific immunoglobulin E (IgE) levels is
      associated with eczema risk in children. National Health and Nutrition
      Examination Survey participants ages 1 to 17 years were asked whether they had
      ever received a diagnosis of eczema from a physician (n = 538). Total and
      specific serum IgE levels for four dietary allergens (egg, cow's milk, peanut,
      and shrimp) and five environmental allergens (dust mite, cat, dog, Aspergillus,
      and Alternaria) were measured. Logistic regression was used to examine the
      association between eczema and IgE levels. In the United States, 10.4 million
      children (15.6%) have a history of eczema. Eczema was more common in black
      children (p < 0.001) and in children from families with higher income and
      education (p = 0.01). The median total IgE levels were higher in children with a
      history of eczema than in those without (66.4 vs 50.6 kU/L, p = 0.004). In
      multivariate analysis adjusted for age, race, sex, family income, household
      education, and physician-diagnosed asthma, eczema was significantly associated
      with sensitization to cat dander (odds ratio [OR] = 1.2, 95% confidence interval
      [CI] 1.05, 1.4, p = 0.009) and dog dander (OR = 1.5, 95% CI, 1.2, 1.7, p <
      0.001). After correction for multiple comparisons, only sensitization to dog
      dander remained significant. U.S. children with eczema are most likely to be
      sensitized to dog dander. Future prospective studies should further explore this
      relationship.

PMID- 24283550
TI  - Adhesive capsulitis: review of imaging and treatment.
AB  - Adhesive capsulitis is one of the most common conditions affecting the shoulder;
      however, early clinical diagnosis can be challenging. Treatment is most effective
      when commenced prior to the onset of capsular thickening and contracture;
      consequently, the role of imaging is increasing. The aim of this review is to
      demonstrate the typical imaging appearances of adhesive capsulitis and to examine
      some of the evidence regarding each of these imaging modalities. An evaluation of
      the various management options available to the clinician is also presented. 

PMID- 24283551
TI  - Bronchial and non-bronchial systemic arteries: value of multidetector CT
      angiography in diagnosis and angiographic embolisation feasibility analysis.
AB  - INTRODUCTION: The aim of this study is to evaluate the diagnostic performance of
      multidetector CT angiography (CTA) in depicting bronchial and non-bronchial
      systemic arteries in patients with haemoptysis and to assess whether this
      modality helps determine the feasibility of angiographic embolisation. MATERIALS
      AND METHODS: Fifty-two patients with haemoptysis between January 2010 and July
      2011 underwent both preoperative multidetector CTA and digital subtraction
      angiography (DSA) imaging. Diagnostic performance of CTA in depicting arteries
      causing haemoptysis was assessed on a per-patient and a per-artery basis. The
      feasibility of the endovascular treatment evaluated by CTA was analysed.
      Sensitivity, specificity, and positive and negative predictive values for those
      analyses were determined. RESULTS: Fifty patients were included in the artery
      presence-number analysis. In the per-patient analysis, neither CTA (P = 0.25) nor
      DSA (P = 1.00) showed statistical difference in the detection of arteries causing
      haemoptysis. The sensitivity, specificity, and positive and negative predictive
      values were 94%, 100%, 100%, and 40%, respectively, for the presence of
      pathologic arteries evaluated by CTA, and 98%, 100%, 100%, and 67%, respectively,
      for DSA. On the per-artery basis, CTA correctly identified 97% (107/110). Fifty
      two patients were included in the feasibility analysis. The performance of CTA in
      predicting the feasibility of angiographic embolisation was not statistically
      different from the treatment performed (P = 1.00). The sensitivity, specificity,
      and positive and negative predictive values were 96%, 80%, 98% and 67%,
      respectively, for CTA. CONCLUSIONS: Multidetector CTA is an accurate imaging
      method in depicting the presence and number of arteries causing haemoptysis. This
      modality is also useful for determining the feasibility of angiographic
      embolisation for haemoptysis.

PMID- 24283552
TI  - CT-guided core biopsy of malignant lung lesions: how many needle passes are
      needed?
AB  - AIM: The study aims to determine the number of needle pass in the CT-guided core
      needle biopsy (CNB) in making a diagnosis of pulmonary malignancy. MATERIALS AND
      METHODS: A total of 434 CNB records were retrospectively reviewed. The specimen
      obtained from each needle pass was put in a formalin container and then labelled
      for separate histopathological reporting. The patients were divided into five
      groups according to the total number of needle passes (n = 1, n = 2, n = 3, n = 4
      and n >= 5). In each of the groups 2-4, it was analysed how many needle passes
      are required before a plateau in diagnostic yield is achieved. RESULTS: CNB
      produced 283 true-positive and 23 false-negative diagnosis of malignancy.
      Cumulative sensitivity significantly (P < 0.05) increased between the first and
      second as well as the second and the third (if done) needle passes, but not
      between the third and fourth ones. CONCLUSION: Three coaxial needle passes might
      be optimal in the diagnosis of lung malignancy.

PMID- 24283553
TI  - The value of CT imaging of Horus in determining the method of mummification and
      the sex of the mummy.
AB  - INTRODUCTION: Radiology was used to determine the sex of a child mummy who had
      conflicting records based on two different translations of a name written in a
      section of papyrus inserted into the mummy wrappings and also to determine the
      type of mummification used to preserve the body. METHODS: Ancient texts of
      Herodotus and Diodorus Siculus were consulted for references to mummification,
      and Nicholson Museum records provided details of the mummy which was examined at
      Central Sydney Imaging using Toshiba Aquilion 64 CT machine (Toshiba Medical
      Systems Corporation, Tochigi, Japan). The original CT scan data were loaded into
      a Vitrea 2 (Vital Images, Minnetonka, MN, USA) workstation at the Victorian
      Institute of Forensic Medicine, Melbourne, Australia, for further study. RESULTS:
      The scans showed that the child had been elaborately mummified according to
      ancient descriptions albeit with one variation. The provenance of the child was
      unknown but stylistically appeared to be from the Greco-Roman Period of ancient
      Egypt. Interpretation of the CT images determined that the child was male, had
      died of unknown cause and had been excerebrated and eviscerated post-mortem when
      the heart was removed. Unexplained inclusions were identified within the abdomen
      and thorax. Broken and displaced ribs showed evidence of a previous endoscopic
      investigation. CONCLUSION: This study provided evidence that CT scanning was an
      excellent non-invasive modality to evaluate ancient mummies in its ability to
      demonstrate fine anatomical detail and identify post-mortem changes. The study
      underlined the role of using current medical practice to determine sex rather
      than relying on ancient texts and uncorroborated opinion.

PMID- 24283554
TI  - Musculoskeletal lymphoma: MRI of bone or soft tissue presentations.
AB  - AIM: To assess the MRI findings of musculoskeletal lymphoma primarily presenting
      clinically as a bone lesion or soft tissue mass. METHODS: Magnetic resonance
      imaging of 23 cases of musculoskeletal lymphoma were retrospectively reviewed.
      Features assessed included tumour location, morphology, signal intensity (SI)
      characteristics, cortical destruction, involvement of multiple anatomic
      compartments, encasement of adjacent neurovascular structures/tendons and
      subcutaneous oedema. RESULTS: Osseous lesions were typically poorly defined and
      hypointense on T1-weighted imaging. T2-weighted SI was usually heterogeneous,
      with 54% of cases having a 'mosaic' pattern of marrow replacement. Ninety-two per
      cent of osseous tumours had cortical abnormalities, most commonly a permeative
      pattern. A periosseous soft tissue cuff was present in 46% of cases while 38% had
      a more significant extraosseous component. All cases of soft tissue lymphoma were
      iso-/slightly hyperintense to muscle on T1-weighted images and hyperintense on T2
      weighted images. Multicompartment involvement by extraosseous tumour was present
      in 75% of cases, and 67% had subcutaneous oedema. Eighty-three per cent of soft
      tissue tumours showed encasement of adjacent structures. Multifocal lymphoma had
      similar morphology and SI characteristics to single-site lesions.
      Histopathologically, there were 21 cases of non-Hodgkin's lymphoma and two of
      Hodgkin's lymphoma. CONCLUSION: Magnetic resonance imaging features of primary
      osseous lymphoma include T2 heterogeneity, a periosseous soft tissue cuff or a
      more substantial mass, and cortical disruption often disproportionate to the
      extent of extraosseous tumour. Features characteristic of soft tissue lymphoma
      include relative homogeneity on T1- and T2-weighted imaging, multicompartment
      involvement and encasement of neurovascular structures.

PMID- 24283555
TI  - 18 FDG PET and PET-CT for the detection of bone metastases in patients with head
      and neck cancer. A meta-analysis.
AB  - INTRODUCTION: We performed a meta-analysis to evaluate (18) FDG PET/PET-CT for
      the detection of bone metastases in patients with head and neck cancer. METHODS:
      We calculated sensitivities, specificities, likelihood ratios, and constructed
      summary receiver operating characteristic curves for PET and PET-CT,
      respectively. We also compared the performance of PET/PET-CT with that of bone
      scintigraphy by analysing studies that had also used bone scintigraphy on the
      same patients. RESULTS: Across 9 PET studies (1621 patients) and 10 PET-CT
      studies (1291 patients), sensitivity and specificity of PET were 0.81 and 0.99,
      and of PET-CT were 0.89 and 0.99, respectively. In 5 comparative studies (1184
      patients), sensitivity and specificity of PET/PET-CT were 0.85 and 0.98, and of
      bone scintigraphy were 0.55 and 0.98, respectively. CONCLUSIONS: (18) FDG PET and
      PET-CT have high sensitivity and accuracy for the detection of bone metastasis in
      patients with head and neck cancer.

PMID- 24283556
TI  - The 'double pituitary hot spot' sign of skull base meningioma on gallium-68
      labelled somatostatin analogue PET.
AB  - Gallium-68 ((68) Ga)-labelled somatostatin analogue imaging by positron emission
      tomography (PET) is increasingly replacing single photon (such as (111) In
      labelled octreotide) imaging in the detection and staging of carcinoid and other
      neuroendocrine tumours. Among other tissues, pituitary uptake of 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate (DOTA-TATE) and other
      somatostatin analogues is physiological. DOTA-TATE also accumulates in
      meningiomas, which have a high density of somatostatin receptor expression. The
      combination of pituitary and skull base meningioma uptake results in a
      characteristic 'double hot spot' appearance, which indicates the presence of a
      meningioma. This is a case of a middle-aged woman who underwent (68) Ga-DOTA-TATE
      PET for confirmation and staging of clinically suspected carcinoid tumour, in
      whom a skull base meningioma was incidentally discovered. With the increasing use
      of PET in the management of neuroendocrine tumours - and the not infrequent
      occurrence of meningiomas - the appearance of meningiomas on somatostatin
      analogue imaging should be one with which reporting clinicians are familiar. 

PMID- 24283557
TI  - More imaging guidelines: a symptom of implementation failure?

PMID- 24283558
TI  - Efficacy of diffusion-weighted imaging and apparent diffusion coefficient
      measurement in the determination of the focal liver lesions.

PMID- 24283559
TI  - Respiratory-gated thoracic radiotherapy: much complexity for how much gain?

PMID- 24283560
TI  - Minimal benefit of respiratory-gated radiation therapy in the management of
      thoracic malignancy.
AB  - BACKGROUND: Respiratory-gated radiotherapy (RGRT) is used in several centres
      around the world. However, there is continuing controversy regarding the benefit
      of this technique. The aims of this study are to quantify the dosimetric benefits
      and the potential predictive factors. METHODS: Thirty-four consecutive patients
      were planned using the RGRT and the Free Breathing (FB) approach and compared
      with regard to target volume coverage and normal tissue parameters. Potential
      predictive factors were also evaluated. RESULTS: Tumour coverage was similar
      94.4% versus 95.5%. Use of RGRT was not associated with a significant reduction
      in spinal cord, oesophagus or cardiac dosimetric parameters. However, it did
      reduce the lung mean dose by 1.33 Gy (P < 0.001) and V20 by 2.2% (P < 0.001).
      Only superior/inferior displacement of >1 cm was predictive of a >5% reduction in
      lung V20 parameter, and these patients all had a gross tumour volume (GTV) of
      <100 cm(3). CONCLUSIONS: The dosimetric benefit of applying RGRT is small when
      applied in an unselected population of patients. Superior/inferior displacement
      of >1 cm for tumours with GTV less than 100 cm(3) may be used to select patients
      who may derive a >5% reduction in lung V20 parameters.

PMID- 24283561
TI  - Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and
      pituitary glands in radiotherapy of nasopharyngeal cancer patients.
AB  - INTRODUCTION: Radiation-induced thyroid dysfunction after radiotherapy for
      nasopharyngeal cancer (NPC) has been reported. This study investigated the
      radiation effects of the thyroid and pituitary glands on thyroid function after
      radiotherapy for NPC. METHODS: Sixty-five NPC patients treated with radiotherapy
      were recruited. Baseline thyroid hormone levels comprising free triiodothyronine
      (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken
      before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated
      radiotherapy plan was generated for each patient. Thyroid and pituitary gland
      dose volume histograms were generated, dividing the patients into four groups:
      high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low
      pituitary doses (HTLP group); low thyroid and high pituitary doses; and low
      thyroid and pituitary doses. Incidence of hypothyroidism was analysed. RESULTS:
      Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary
      doses, respectively. At 18 months, 23.1% of patients manifested various types of
      hypothyroidism. The HTHP group showed the highest incidence (83.3%) of
      hypothyroidism, followed by the HTLP group (50%). CONCLUSIONS: NPC patients with
      high thyroid and pituitary gland doses carried the highest risk of abnormal
      thyroid physiology. The dose to the thyroid was more influential than the
      pituitary dose at 18 months after radiotherapy, and therefore more attention
      should be given to the thyroid gland in radiotherapy planning.

PMID- 24283562
TI  - Phase I trials involving radiation therapy, quantifying the risks.
AB  - INTRODUCTION: Over one third of cancer patients receive radiation therapy (RT) at
      some point. Our purpose was to quantify the risks to patients associated with
      enrolment onto RT-based phase I trials. METHODS: All phase I and phase I/II
      clinical trials involving RT published in English between 2001 and 2010 were
      identified via a PubMed search. For pragmatic reasons, we focused on trials from
      2001, 2005 and 2009. For each trial we calculated a 'toxicity ratio' equal to the
      number of grade 3/4/5 toxic events divided by the number of patients in the
      trial. Linear regression was used to determine which variables were associated
      with higher toxicity ratios. RESULTS: There were a total of 33 treatment-related
      deaths, and 1812 acute grade 3/4 toxicities among the 2994 subjects in 98 trials.
      The median toxicity ratio over 98 trials was 0.46 (95% confidence interval (CI)
      0.34 to 0.58). Multivariate regression analysis showed that toxicity ratios were
      significantly higher in trials with chemotherapy (P = 0.002) and in trials for
      cancers of the head-and-neck (P < 0.001). The median toxicity ratio in
      chemotherapy trials was 0.60 (95% CI: 0.48 to 0.72) compared with trials without
      chemotherapy 0.08 (95% CI: 0.03 to 0.13). CONCLUSIONS: Although the risk of grade
      5 toxicity is low, the risk of major toxicity is significant in phase I RT
      trials. These values are comparable to published risk estimates for phase I non
      RT trials.

PMID- 24283563
TI  - Prostate bed motion may cause geographic miss in post-prostatectomy image-guided
      intensity-modulated radiotherapy.
AB  - INTRODUCTION: There is little data to guide radiation oncologists on appropriate
      margin selection in the post-prostatectomy setting. The aim of this study was to
      quantify interfraction variation in motion of the prostate bed to determine these
      margins. METHODS: The superior and inferior surgical clips in the prostate bed
      were tracked on pretreatment cone beam CT images (n = 377) for 40 patients who
      had received post-prostatectomy radiotherapy. Prostate bed motion was calculated
      for the upper and lower segments by measuring the position of surgical clips
      located close to midline relative to bony anatomy in the axial (translational)
      and sagittal (tilt) planes. The frequency of potential geographic misses was
      calculated for either 1 cm or 0.5 cm posterior planning target volume margins.
      RESULTS: The mean magnitude of movement of the prostate bed in the anterior
      posterior, superior-inferior and left-right planes, respectively, were as
      follows: upper portion, 0.50 cm, 0.28 cm, 0.10 cm; lower portion, 0.18 cm, 0.18
      cm, 0.08 cm. The random and systematic errors, respectively, of the prostate bed
      motion in the anterior-posterior, superior-inferior and left-right planes,
      respectively, were as follows: upper portion, 0.47 cm and 0.50 cm, 0.28 cm and
      0.27 cm, 0.11 cm and 0.11 cm; lower portion, 0.17 cm and 0.18 cm, 0.17 cm and
      0.19 cm, 0.08 cm and 0.10 cm. Most geographic misses occurred in the upper
      prostate bed in the anterior-posterior plane. The median prostate bed tilt was
      1.8 degrees  (range -23.4 degrees  to 42.3 degrees ). CONCLUSIONS: Variability
      was seen in all planes for the movement of both surgical clips. The greatest
      movement occurred in the anterior-posterior plane in the upper prostate bed,
      which could cause geographic miss of treatment delivery. The variability in the
      movement of the superior and inferior clips indicates a prostate bed tilt that
      would be difficult to correct with standard online matching techniques. This
      creates a strong argument for using anisotropic planning target volume margins in
      post-prostatectomy radiotherapy.

PMID- 24283564
TI  - Revised radiobiological modelling of the contribution of synchronous chemotherapy
      to the rate of grades 3-4 mucositis in head and neck cancer.
AB  - INTRODUCTION: Biological effective dose (BED) calculations modelled on reduced
      accelerated repopulation when synchronous chemotherapy is delivered significantly
      correlate with observed differences in local control in randomised trials of
      platinum-based chemoradiation. The purpose of this study was to examine whether a
      similar relationship existed in the context of grades 3-4 mucositis. METHODS:
      Biological effective dose from radiotherapy and synchronous chemotherapy was
      calculated using three different models: AB using the additional BED attributable
      to chemotherapy and standard repopulation parameters; zero repopulation (ZRP)
      using zero correction for repopulation; and variable t(p) (Vt(p)) using a
      variable doubling time for mucosal stem cell repopulation. The correlation
      between the percentage change in biological effective dose between trial arms,
      and the observed percentage change in the rate of grades 3-4 mucositis was
      examined by using the Pearson product-moment correlation. RESULTS: With the AB
      model, there were no significant correlations with observed differences in rates
      of grades 3-4 mucositis. With either the ZRP or Vt(p) models, significant
      correlations were observed. A value of 5 days for the doubling time during
      repopulation (T(p)) was associated with the most significant correlation (P =
      0.002). CONCLUSION: Models where the dose lost due to accelerated repopulation is
      reduced imply a therapeutic loss from the use of synchronous chemotherapy when
      only local control and the rate of acute grades 3-4 mucositis are considered.

PMID- 24283567
TI  - Selective growth of MoS2 for proton exchange membranes with extremely high
      selectivity.
AB  - Proton conductivity and methanol permeability are the most important transport
      properties of proton exchange membranes (PEMs). The ratio of proton conductivity
      to methanol permeability is usually called selectivity. Herein, a novel strategy
      of in situ growth of MoS2 is employed to prepare MoS2/Nafion composite membranes
      for highly selective PEM. The strong interactions between the Mo precursor
      ((NH4)2MoS4) and Nafion's sulfonic groups in a suitable solvent environment (DMF)
      probably lead to a selective growth of MoS2 flakes mainly around the ionic
      clusters of the resultant MoS2/Nafion composite membrane. Therefore, it would
      significantly promote the aggregation and hence lead to a better connectivity of
      these ionic clusters, which favors the increase in proton conductivity.
      Meanwhile, the existence of MoS2 in the ionic channels effectively prevents
      methanol transporting through the PEM, contributing to the dramatic decrease in
      the methanol permeability. Consequently, the MoS2/Nafion composite membranes
      exhibit greatly increased selectivity. Under some severe conditions, such as 50 
      degrees C with 80 v/v% of methanol concentration, an increase in the membrane
      selectivity by nearly 2 orders of magnitude compared with that of the recast
      Nafion membrane could be achieved here, proving our method as a very promising
      way to prepare high-performance PEMs. All these conclusions are confirmed by
      various characterizations, such as (FE-) SEM, TEM, AFM, IR, Raman, TGA, XRD, etc.

PMID- 24283568
TI  - Treatment of circumferential defects with osseoconductive xenografts of different
      porosities: a histological, histometric, resonance frequency analysis, and micro
      CT study in dogs.
AB  - BACKGROUND: Finding the most effective method of minimizing the gap effect in
      alveolar crest remodeling constitutes a clinical challenge for immediate implant
      technique. PURPOSE: To evaluate the effectiveness of osseoconductive xenografts
      with different porosities in the crestal bone region, with and without guided
      bone regeneration, over immediate implant installation. MATERIALS AND METHODS:
      Five bone defects (6 mm in diameter/4 mm depth) were prepared on one side of the
      mandibles of twelve dogs. Implants of 3.3 * 10 mm were installed on the mesial
      side of each defect, providing a 2.7-mm distal gap. Defects were randomly filled
      with autogenous bone, coagulum, a deproteinized bovine bone mineral (DBBM) block,
      a DBBM sponge, or DBBM granules. The same procedures were performed on the
      opposite side after 8 weeks. Collagen membranes were used to cover the defects on
      half of the sides. The animals were sacrificed after 8 weeks. The outcomes were
      evaluated by histology, histomorphometric analysis, resonance frequency analysis,
      and micro-CT analysis. RESULTS: The histomorphometry showed the DBBM sponge to
      provide similar bone formation to autogenous bone at 8 weeks without a membrane.
      The coagulum rendered better bone formation at 16 weeks (membrane) (p < .05). The
      DBBM block exhibited the poorest results between treatments (8 and 16 weeks, with
      or without membrane). Micro-CT analysis revealed increasing bone surface values
      in sites with DBBM granules, followed by the DBBM sponge (8 weeks without
      membrane) and autogenous bone at 8 weeks with membrane (p < .05). Porosity
      analysis of the biomaterials showed the highest number, volume, and surface area
      of closed pores in DBBM granules. The DBBM block presented the highest volume of
      open pores, open porosity, and total porosity. CONCLUSIONS: The high-porosity
      block (DBBM block) failed to provide greater bone repair within the defect.
      Biomaterials with lower porosity (DBBM sponge and granules) showed similar or
      higher bone formation when compared with autogenous bone.

PMID- 24283569
TI  - Pneumatosis intestinalis following pediatric live-related liver transplant: a
      case report and successful conservative approach.
AB  - PI has been rarely reported following pediatric live-related liver
      transplantation. Such a disorder is characterized by accumulation of gas in the
      bowel wall. The cause of PI has not been yet established; however, it has been
      strongly linked with steroid therapy. In this report, we present a case of PI
      following pediatric live-related liver transplantation that has been successfully
      managed conservatively. 

PMID- 24283571
TI  - Surface-exposed proteins of pathogenic mycobacteria and the role of cu-zn
      superoxide dismutase in macrophages and neutrophil survival.
AB  - Pathogenic mycobacteria are important agents causing human disease. Mycobacterium
      avium subsp. hominissuis (M. avium) is a species of recalcitrant environmental
      pathogen. The bacterium forms robust biofilms that allow it to colonize and
      persist in austere environments, such as residential and commercial water
      systems. M. avium is also an opportunistic pathogen that is a significant source
      of mortality for immune-compromised individuals. Proteins exposed at the
      bacterial surface play a central role in mediating the relationship between the
      bacterium and its environment. The processes underlying both biofilm formation
      and pathogenesis are directly dependent on this essential subset of the bacterial
      proteome. Therefore, the characterization of the surface-exposed proteome is an
      important step towards an improved understanding of the mycobacterial biology and
      pathogenesis. Here we examined the complement of surface exposed proteins from
      Mycobacterium avium 104, a clinical isolate and reference strain of Mycobacterium
      avium subsp. hominissuis. To profile the surface-exposed proteins of viable M.
      avium 104, bacteria were covalently labeled with a membrane impermeable
      biotinylation reagent and labeled proteins were affinity purified via the biotin
      streptavidin interaction. The results provide a helpful snapshot of the surface
      exposed proteome of this frequently utilized reference strain of M. avium. A Cu
      Zn SOD knockout mutant, MAV_2043, a surface identified protein, was evaluated
      regarding its role in the survival in both macrophages and neutrophils. 

PMID- 24283572
TI  - Optimal phosphate control: still an unmet need in chronic kidney disease
      patients.
AB  - Reduction of phosphate levels has traditionally been considered a mainstay
      treatment for patients with chronic kidney disease (CKD). Unfortunately, the
      treatment of hyperphosphatemia is far from being satisfactory. Available
      phosphate binders have limited efficacy, forcing the consumption of many tablets
      in order to achieve mild-to-moderate effect or low tolerability. Moreover, even
      if calcium-free phosphate binders, such as sevelamer and lanthanum carbonate,
      decrease serum phosphate levels without affecting serum calcium concentration,
      they do not significantly reduce circulating parathyroid hormone (PTH). The
      higher phosphate-binding efficacy of lanthanum carbonate should be balanced with
      the accumulation in bones and the lack of pleiotropic effects on lipid metabolism
      and inflammation. However, the fact that lanthanum carbonate seems to decrease
      the rate of development of vascular calcifications more or less similar to
      sevelamer suggests that phosphate control could actually be the key factor to
      improve patient outcome. New iron-based phosphate binders are undergoing clinical
      development. In addition to phosphate binding, they can be useful to treat
      anemia, and are undergoing Phase II clinical development for this indication.
      This could be of clinical importance particularly in CKD patients not on
      dialysis, avoiding the need for extra oral iron administration, and favoring
      compliance. In conclusion, the control of phosphate retention should still be
      considered an unmet medical need for CKD patients. 

PMID- 24283570
TI  - Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene
      expression during epithelial-to-mesenchymal transition of breast cancer cells.
AB  - INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) promotes cell migration
      and is important in metastasis. Cellular proliferation is often downregulated
      during EMT, and the reverse transition (MET) in metastases appears to be required
      for restoration of proliferation in secondary tumors. We studied the interplay
      between EMT and proliferation control by MYB in breast cancer cells. METHODS:
      MYB, ZEB1, and CDH1 expression levels were manipulated by lentiviral small
      hairpin RNA (shRNA)-mediated knockdown/overexpression, and verified with Western
      blotting, immunocytochemistry, and qRT-PCR. Proliferation was assessed with
      bromodeoxyuridine pulse labeling and flow cytometry, and sulforhodamine B assays.
      EMT was induced with epidermal growth factor for 9 days or by exposure to hypoxia
      (1% oxygen) for up to 5 days, and assessed with qRT-PCR, cell morphology, and
      colony morphology. Protein expression in human breast cancers was assessed with
      immunohistochemistry. ZEB1-MYB promoter binding and repression were determined
      with Chromatin Immunoprecipitation Assay and a luciferase reporter assay,
      respectively. Student paired t tests, Mann-Whitney, and repeated measures two-way
      ANOVA tests determined statistical significance (P < 0.05). RESULTS: Parental
      PMC42-ET cells displayed higher expression of ZEB1 and lower expression of MYB
      than did the PMC42-LA epithelial variant. Knockdown of ZEB1 in PMC42-ET and MDA
      MB-231 cells caused increased expression of MYB and a transition to a more
      epithelial phenotype, which in PMC42-ET cells was coupled with increased
      proliferation. Indeed, we observed an inverse relation between MYB and ZEB1
      expression in two in vitro EMT cell models, in matched human breast tumors and
      lymph node metastases, and in human breast cancer cell lines. Knockdown of MYB in
      PMC42-LA cells (MYBsh-LA) led to morphologic changes and protein expression
      consistent with an EMT. ZEB1 expression was raised in MYBsh-LA cells and
      significantly repressed in MYB-overexpressing MDA-MB-231 cells, which also showed
      reduced random migration and a shift from mesenchymal to epithelial colony
      morphology in two dimensional monolayer cultures. Finally, we detected binding of
      ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB
      promoter activity. CONCLUSIONS: This work identifies ZEB1 as a transcriptional
      repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation,
      providing a mechanism through which proliferation and the epithelial phenotype
      may be coordinately modulated in breast cancer cells.

PMID- 24283573
TI  - Facile solvothermal preparation of monodisperse gold nanoparticles and their
      engineered assembly of ferritin-gold nanoclusters.
AB  - Herein, we report a quick and simple synthesis of water-soluble gold
      nanoparticles using a HAuCl4 and oleylamine mixture. Oleylamine serves as a
      reduction agent as well as a stabilizer for nanoparticle surfaces. The particle
      sizes can be adjusted by modulating reaction temperature and time. Solvothermal
      reduction of HAuCl4 with oleylamine can be confirmed by measuring the product in
      Fourier transform infrared (FTIR) spectroscopy. The plasmon band shifting from
      yellow to red confirms a nanosized particle formation. Amide bonds on the surface
      of the nanoparticles formed hydrogen bonds with one another, resulting in a
      hydrophobic monolayer. Particles dispersed well in nonpolar organic solvents,
      such as in hexane or toluene, by brief sonication. Next, we demonstrated the
      transfer of gold nanoparticles into water by lipid capsulation using 1-myristoyl
      2-hydroxy-sn-glycero-3-phosphocholine (MHPC), 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-(methoxy polyethylene glycol)-2000 (DPPE-PEG2k), and 1,2
      dioleoyl-sn-glycero-3-N-{5-amino-1-carboxypentyl}iminodiacetic acid succinyl
      nickel salt [DGS-NTA(Ni)]. The particle concentration can be obtained using an
      absorbance in ultraviolet-visible (UV-vis) spectra (at 420 nm). Instrumental
      analyses using transmission electron microscopy (TEM), energy-dispersive X-ray
      (EDX) analysis, dynamic light scattering (DLS), and FTIR confirmed successful
      production of gold nanoparticles and fair solubility in water. Prepared gold
      particles were selectively clustered via engineered ferritin nanocages that
      provide multiple conjugation moieties. A total of 5-6 gold nanoparticles were
      clustered on a single ferritin nanocage confirmed in TEM. Reported solvothermal
      synthesis and preparation of gold nanoclusters may serve as an efficient,
      alternate way of preparing water-soluble gold nanoparticles, which can be used in
      a wide variety of biomedical applications. 

PMID- 24283574
TI  - DNA/protein binding, molecular docking, and in vitro anticancer activity of some
      thioether-dipyrrinato complexes.
AB  - Syntheses and characterizations of the arene ruthenium [(eta(6)-C6H6)RuCl(4
      mtdpm)] (1), [(eta(6)-p-MeC6H4Pr(i))RuCl(4-mtdpm)] (2), and structurally
      analogous rhodium/iridium complexes [(eta(5)-C5Me5)RhCl(4-mtdpm)] (3) and
      [(eta(5)-C5Me5)IrCl(4-mtdpm)] (4) [4-mtdpm = 5-(4
      methylthiophenyl)dipyrromethene] have been reported. Their identities have been
      established by satisfactory elemental analyses, electrospray ionization-mass
      spectrometry (ESI-MS), FT-IR, NMR ((1)H, (13)C), UV/vis, emission spectral, and
      electrochemical studies. Structure of the representative complex 3 has been
      authenticated by X-ray single crystal analyses. The complexes 1-4 effectively
      bind with calf thymus DNA (CT DNA) through intercalative/electrostatic
      interactions. In addition, these exhibit significant cytotoxicity toward Dalton
      lymphoma (DL) cell line and cause static quenching of the bovine serum albumin
      (BSA) fluorophore. The antiproliferative activity, morphological changes, and
      apoptosis have been evaluated by MTT assay, acridine orange/ethidium bromide
      (AO/EtBr) fluorescence staining, and DNA ladder assay. Mode of interaction of the
      complexes with DNA/protein has also been supported by molecular docking. Various
      studies revealed remarkable decrease in the in vitro DL cell proliferation and
      induction of the apoptosis by 1-4, which lies in the order 2 > 1 > 4 > 3. 

PMID- 24283575
TI  - 5-HT1 receptors in migraine pathophysiology and treatment.
AB  - Migraine is a frequent paroxysmal headache disorder of unknown aetiology. Genetic
      factors may control attack frequency and possibly attack severity. Serotonin1D (5
      HT1Dbeta ) receptors have a prominent position within the final common pathway of
      the mechanisms involved in the headache and associated symptoms. Stimulation of
      these receptors by selective 5-HT1Dbeta receptor agonists such as sumatriptan and
      newer compounds including MK-462 and 311C90, rapidly and fully blocks the
      symptoms of the headache phase. The efficacy depends on factors such as timing of
      administration during or before the headache, speed of initial rise of drug
      plasma levels, and possibly degree of brain penetration. All agonists at S
      HT1Dbeta receptors share a short duration of action resulting in recurrence of
      the headache symptoms within 24 h in about one-third of attacks in clinical
      trials. The risk for headache recurrence seems patient dependent: about 10% of
      patients treating multiple attacks experience headache recurrence in every
      treated attack, whereas 40% never experience recurrence. These differences are
      not related to simple pharmacokinetic differences between patients or drugs.
      Increasing plasma half-life of the drug will most likely not reduce the risk of
      recurrence. "Breakthrough of peripheral suppressive effect" with an ongoing
      "central migraine generator", rather than the occurrence of a new attack, seems
      to be the most likely underlying mechanism for headache recurrence. In a minority
      of, possibly predisposed, patients, use of sumatriptan may induce increase of
      attack frequency. Four mechanisms have been suggested for the antimigraine action
      of 5-HT1Dbeta receptor agonists: (1) vasoconstriction of cranial, most likely
      meningeal and dural blood vessels; (2) inhibition of release of vasoactive
      neuropeptides from perivascular trigeminal nerve terminals within dura mater and
      meninges; (3) blockade of trigeminal nerve terminal depolarization; and (4)
      central inhibition within the trigeminal nucleus caudatus in the brainstem. Which
      of these mechanisms is the most important, and whether or not vasoconstrictor
      action is necessary for antimigraine efficacy, is currently under extensive
      investigation. At this point all drugs with proven antimigraine efficacy share
      the ability to contract blood vessels and thus all feature also the potential
      risk of causing vasoconstriction of coronary vessels. In relation herewith, major
      efforts are put into the search for "the antimigraine receptor" and which
      receptor subtype mediates which action of sumatriptan-like drugs. At this point,
      the 5-HT1Dbeta receptor subtype is thought to mediate vasoconstriction. Some
      investigators feel that the 5-HT1Dalpha receptor subtype mediates the neuronal
      effects of sumatriptan, while others are much less convinced about the
      physiological role of this subtype of receptor. Further research into receptor
      subtype specificity and affinity of compounds may promote the development of even
      better antimigraine drugs. 

PMID- 24283576
TI  - Hereditary juvenile parkinsonism with pyramidal signs and mental retardation.
AB  - We describe two patients who developed, in the first and second decades of life,
      mental retardation, some limitation of up gaze, poorly levodopa-responsive
      parkinsonism and pyramidal signs. Recessive inheritance is suggested by the fact
      that they were subsequently found to be first cousins from consanguineous unions.
      A number of different possible diagnoses were considered, but despite extensive
      investigation these patients, who are both still living, thus far appear to be
      unique. In particular, unlike most cases of alleged "pallido-pyramidal disease"
      in the literature, we do not feel it justifiable to use this denomination in the
      absence of either pathological or in vivo imaging evidence of pallidal
      involvement. 

PMID- 24283577
TI  - Decreased CSF levels of homovanillic acid in ALS patients.
AB  - Levels of homovanillic acid (MVA) were measured in lumbar cerebrospinal fluid
      from 24 patients affected by amyotrophic lateral sclerosis (ALS) and compared
      with those found in 11 patients with Parkinson's disease (PD) and 10 patients
      with lumbar disc herniations who served as controls. Mean HVA levels were
      significantly decreased in ALS and PD patients. These findings are consistent
      with impairment of central dopaminergic systems in ALS as well as suggesting
      degeneration of neuroanatomical structures other than motor neurons. 

PMID- 24283578
TI  - Intracranial pressure is a fraction of arterial blood pressure.
AB  - The relation between cerebrospinal fluid pressure (pcsf ) and arterial blood
      pressure (pa ) was studied in pigs and in rabbits before and after an ischemia
      induced impairment of the cerebral autoregulation, in order to predict the effect
      of changes of pa on the pcsf . Before the ischemic brain episode no clear
      correlation between pa and pcsf was found. A close dependence emerged after the
      ischemic episode, and after each change in pa the pcsf assumed immediately a new
      stationary level. The results suggest that intracranial pressure is at any moment
      a fraction of arterial blood pressure quantitatively determined by the
      coordinated action of cerebrovascular resistance, i.e. arteriolar resistance Ra ,
      regulated by vasomotor tonus, and venous resistance Rv , which is mechanically
      passive in the same manner as a Starling resistor device. The relation is given
      by pcsf = pa [1 + (Ra /pv )](-1) . Induced changes in pa have different effects
      on pcsf . However, this effect may be predicted to some extent because the
      relation between pcsf and pa may be represented mathematically as a rectangular
      hyperbola. This observation may be of relevance in neurological intensive care.
      Changes in arterial blood pressure are known to influence intracranial pressure
      in patients with deranged intracranial dynamics, as in the case of severe head
      injury. In clinical practice, both raising systemic arterial blood pressure in
      order to preserve cerebral perfusion pressure and induced arterial hypotension to
      reduce hydrostatic capillary pressure with consequent reduction of brain edema
      have been used in the management of patients with severe brain injury. While
      theoretical models of biological systems often have a limited value in practice
      because of inability to measure the relevant parameters from clinical data, the
      ratio of cerebrovascular resistances may be calculated at the bedside. 

PMID- 24283579
TI  - Prognosis of ischaemic stroke - a multivariate analysis.
AB  - Paucity of studies on the prognosis of ischaemic stroke prompted this study.
      Sixty-seven patients with CT-proven infarction were studied after a mean duration
      of 9 days to evaluate the role of a number of clinical, CT scan and evoked
      potential parameters in predicting the prognosis. Their mean age was 53 (range 22
      82) years and 16 were females. Four of these patients died and 20 had poor
      recovery. Out of 24 clinical, CT scan and evoked potential parameters analysed by
      univariate analysis, 11 variables were found to be significant These were
      Canadian Neurological Scale, Glasgow Coma Scale (GCS), Motoricity Index, muscle
      tone, tendon reflex, incontinence, sensations, motor area involvement on CT scan,
      size of infarction, motor evoked potential and somatosensory evoked potential.
      Multivariate logistic regression analysis was employed to study the combined
      effect of different variables on the outcome. The best model included past
      history of stroke, GCS, pulse pressure and involvement of motor area on CT scan.
      The model proposed by us is simple and useful for predicting 3 month outcome of
      ischaemic stroke. A larger study is recommended to confirm these findings.- 

PMID- 24283580
TI  - Post-stroke pathological crying: frequency and correlation to depression.
AB  - While pathological crying has classically been described as a disturbance of the
      motor concomitants of emotional affect that is unrelated to mood, recent studies
      indicate that there may in fact be a correlation. We therefore undertook a study
      of post-stroke pathological crying in relation to mood score/depression and
      lesion site in an unselected stroke population the first year following stroke.
      The study population comprised 211 patients with first ever stroke (median age 69
      years, range 25-80). The patients were included in the study within 7 days of the
      onset of stroke, and follow-up examinations were made at 1 month, 6 months and 1
      year. Computerized tomography brain scans were obtained on Days 5-10. The
      frequency of pathological crying was 14% at 1 month, 10% at 6 months and 11% at 1
      year. The overall 1 year incidence was 19%. Pathological crying correlated
      significantly to mood score and post-stroke depression (p < 0.005), as well as to
      lesion size (p < 0.05), Barthel Index (p < 0.05), Motricity Index (p < 0.005) and
      intellectual impairment (p < 0.05), but not to lesion location, sex, age, history
      of stroke or depression, predisposing disease or social distress before the
      stroke incident Post-stroke pathological crying was common and persistent in 11%
      of patients at 1 year and correlated strongly to mood score and post-stroke
      depression. The indication for treatment of pathological crying is therefore
      further strengthened. 

PMID- 24283581
TI  - Intraspinal endometriosis as a possible cause of recurrent back pain and leg
      monoparesis.
AB  - Recurrent back pain and leg monoparesis in a 38 year old woman could be traced
      back to a focus of intraspinal endometriosis. Upon admission, neurological
      examination revealed multiple sensory deficits and a proximal spastic paresis of
      the left leg. The patient complained about backache, which spontaneously
      disappeared some days later. History taking disclosed a relationship between the
      transient symptomatology and the menstrual cycle. Magnetic resonance imaging of
      the spine demonstrated a signal-intense intraspinal structure at the Th 8/9 level
      on the 25th day of the menstrual cycle. On follow-up examination at the beginning
      of the cycle the previously detected structure had vanished. Intraspinal
      endometriosis was confirmed by gynecological demonstration of additional
      endometriosis of the left ovary as well as positive response to treatment with a
      gonadotrophin releasing hormone analog. 

PMID- 24283583
TI  - Reforming biobank consent policy: a necessary move away from broad consent toward
      dynamic consent.

PMID- 24283584
TI  - TERT genetic polymorphism rs2736100 was associated with lung cancer: a meta
      analysis based on 14,492 subjects.
AB  - BACKGROUND: Previous studies focused on the association of the telomerase reverse
      transcriptase (TERT) gene polymorphism rs2736100 with lung cancer did not reach
      the same conclusion. In the present study, we performed a meta-analysis to
      systematically summarize the possible association between TERT polymorphism
      rs2736100 and the risk for lung cancer. METHOD: We conducted a search of case
      control studies on the association of TERT with susceptibility to lung cancer in
      PubMed, EMBASE, ISI Web of Science, Wanfang database in China, and Chinese
      National Knowledge Infrastructure (CNKI) databases. Data from eligible studies
      were extracted for meta-analysis. Lung cancer risk associated with rs2736100 was
      estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs).
      RESULTS: Six independent case-control studies on rs2736100 were included in our
      meta-analysis. Our results showed that rs2736100 was associated with the risk of
      lung cancer not only in an additive model (OR=1.19, 95% CI: 1.04-1.35; p=0.01),
      but also in a dominant model (OR=1.14, 95% CI: 1.01-1.28; p=0.03). CONCLUSIONS:
      This meta-analysis suggests that rs2736100 is associated with the risk of lung
      cancer.

PMID- 24283585
TI  - Rhodium(II)-catalyzed stereoselective synthesis of allylsilanes.
AB  - The rhodium-catalyzed decomposition of 2-(triisopropylsilyl)ethyl aryl- and
      vinyldiazoacetates results in the stereoselective formation of Z-allylsilanes.
      The transformation is considered to proceed by silyl-directed intramolecular C-H
      functionalization to form a beta-lactone intermediate followed by a silyl
      activated extrusion of carbon dioxide. 

PMID- 24283586
TI  - Production and characterization of recombinant glucose oxidase from Aspergillus
      niger expressed in Pichia pastoris.
AB  - Recombinant glucose oxidase from Aspergillus niger expressed in Pichia pastoris
      by fed-batch fermentation was purified and assessed with 1.26 purification fold
      to homogeneity using Q-Sepharose F.F. chromatography. The enzyme was determined
      by SDS-PAGE and gradient PAGE, which showed a dimeric form of 150 kDa. The
      purified rGOD was proved to be a glycoprotein, and the content of which was
      estimated to be 36.7 and 25.14% by phenol-sulfuric acid and anthrone-sulfuric
      acid methods. Characteristics demonstrated that the highest activity was in pH
      6.0 at 40 degrees C and was stable at a broad pH range from 4.0 to 9.0 at 55
      degrees C or below. The optimum substrate for this enzyme was d-glucose, and the
      Km was 21.06 mmol l(-1) as well as the Vmax was 359 MUmol min(-1) mg(-1). rGOD
      possessed high resistance to various chemicals except for Hg(2+), Fe(2+), Ag(+),
      Cu(2+), 1,4-dithiothreitol, sodium dodecyl sulfate and ascorbic acid. In
      addition, the inhibitors also exhibited intensive fluorescence quenching effect
      on rGOD. SIGNIFICANCE AND IMPACT OF THE STUDY: Glucose oxidase is a very
      important enzyme produced by several species. However, large-scale applications
      have always been postponed by its complexity in fermentation and purification.
      Our research focused on developing new purification strategy of recombinant GOD
      from A. niger expressed in P. pastoris. Here, we described this novel one-step
      purification method and subsequent research in the characteristics of rGOD which
      showed different results from previous work. These can open new opportunities to
      increase its application.

PMID- 24283587
TI  - Catheter-free method is sufficient for preparation for transnasal endoscopy:
      randomized controlled trial.
AB  - BACKGROUND AND AIM: Although transnasal endoscopy (TNE) is generally a
      comfortable and safe procedure, it has some disadvantages, such as complicated
      preprocessing and occasional repulsion reaction during catheterization. In an
      attempt to simplify the preprocessing method, the efficacy of a catheter-free
      method in which a catheter is not inserted into the nasal cavity was assessed.
      METHODS: The present study was a prospective, open-label, single-center,
      randomized controlled study with parallel assignment allocation 1:1. Between
      March 2009 and August 2009, a total of 93 TNE-naive patients were enrolled and
      randomized. Patients were prospectively randomized into two groups (catheter-free
      vs catheter-insertion method). Patients who prepared according to the catheter
      free method and who were unsuccessful underwent the catheter-insertion method.
      Clinical characteristics, success rate, complications, vital signs,
      acceptability, and tolerability were assessed and compared. RESULTS: Success
      rates of the catheter-free and catheter-insertion methods were 88% (n=44) and 88%
      (n=38) (P>0.05), respectively. Causes of failure in the catheter-free method
      included severe rhinalgia (n=1, 2%) and narrowing of the nasal cavity (n=5, 10%).
      Causes of failure in the catheter-insertion method included narrowing of the
      nasal cavity (n=5, 11%). Six patients whose TNE failed with the catheter-free
      method also experienced failed TNE with the catheter-insertion method. There were
      no statistical differences in vital signs, acceptability, and tolerability.
      CONCLUSION: The catheter-free method is sufficient for preparation for TNE. The
      success rate of TNE depends more on the structure of the nasal cavity than the
      preprocessing method.

PMID- 24283589
TI  - Platelet HPA-1 a/HPA-1 b polymorphism and the risk of periprocedural myocardial
      infarction in patients undergoing elective PCI.
AB  - Periprocedural myocardial infarction (PMI) represents a relatively common
      complication of percutaneous coronary intervention (PCI) and large interests have
      been focused on platelets in order to prevent such a complication. The single
      nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related
      to an increased platelet reactivity, a lower response to antiplatelet agents and
      higher risk of stent restenosis. Therefore, aim of our study was to evaluate the
      impact of this polymorphism on PMI in elective patients undergoing PCI. Our
      population is represented by 422 consecutive patients with cardiac biomarkers
      within normality undergoing elective PCI. We measured cardiac biomarkers (CK-MB
      and Troponin I) at baseline, and 8, 24 and 48 hours after the procedure. For all
      subjects, we performed genetic analysis to assess the presence of Leu33Pro
      polymorphism. A total of 136 patients (32.2%) were polymorphic. Those patients
      were younger (p = 0.03) and more often dislypidemic (p = 0.01). Angiographic
      features did not differ according to genetic status. Pharmacological treatment
      pre and during angioplasty was similar. PCI-related complications did not differ
      according to genotype, with the only exception of higher rate of distal
      embolization in polymorphic patients. However, Leu33Pro polymorphism was not
      associated with increased risk of periprocedural myonecrosis and PMI even after
      correction for baseline differences, (respectively OR = 1.22 [0.81-1.84], p =
      0.34 for myonecrosis and OR = 1.66 [0.85-3.23]; p = 0.14 for PMI). At subgroup
      analysis, the Leu33Pro substitution was associated with higher risk of PMI only
      among diabetics (adjusted OR = 4.46 [1.12-17.76], p = 0.03). Among patients
      undergoing elective PCI, the polymorphism Leu33Pro of platelet glycoprotein IIIa
      is associated with increased risk of PMI only in diabetic patients.

PMID- 24283588
TI  - Bioactive lysophospholipids: role in regulation of aqueous humor outflow and
      intraocular pressure in the context of pathobiology and therapy of glaucoma.
AB  - Homeostasis of aqueous humor (AH) outflow and intraocular pressure (IOP) is
      essential for normal vision. Impaired AH outflow through the trabecular meshwork
      (TM) and a resultant elevation in IOP are common changes in primary open-angle
      glaucoma (POAG), which is the most prevalent form of glaucoma. Although elevated
      IOP has been recognized as a definitive risk factor for POAG and lowering
      elevated IOP remains a mainstay for glaucoma treatment, little is known about the
      molecular mechanisms, especially external cues and intracellular pathways,
      involved in the regulation of AH outflow in both normal and glaucomatous eyes. In
      addition, despite the recognition that increased resistance to AH outflow via the
      conventional pathway consisting of TM and Schlemm's canal is the main cause for
      elevated IOP, there are no clinically approved drugs that target the conventional
      pathway to lower IOP in glaucoma patients. The aim of this article is to briefly
      review published work on the importance of bioactive lysophospholipids (eg,
      lysophosphatidic acid and sphingosine-1-phosphate), their receptors, metabolism,
      signaling, and role in the regulation of AH outflow via the TM and IOP, and to
      discuss pharmacological targeting of key proteins in the lysophospholipid
      signaling pathways to lower IOP in glaucoma patients.

PMID- 24283591
TI  - Is BP lowering during acute intracerebral hemorrhage safe?

PMID- 24283590
TI  - Identification of PLX4032-resistance mechanisms and implications for novel RAF
      inhibitors.
AB  - BRAF inhibitors improve melanoma patient survival, but resistance invariably
      develops. Here we report the discovery of a novel BRAF mutation that confers
      resistance to PLX4032 employing whole-exome sequencing of drug-resistant
      BRAF(V600K) melanoma cells. We further describe a new screening approach, a
      genome-wide piggyBac mutagenesis screen that revealed clinically relevant
      aberrations (N-terminal BRAF truncations and CRAF overexpression). The novel BRAF
      mutation, a Leu505 to His substitution (BRAF(L505H) ), is the first resistance
      conferring second-site mutation identified in BRAF mutant cells. The mutation
      replaces a small nonpolar amino acid at the BRAF-PLX4032 interface with a larger
      polar residue. Moreover, we show that BRAF(L505H) , found in human prostate
      cancer, is itself a MAPK-activating, PLX4032-resistant oncogenic mutation.
      Lastly, we demonstrate that the PLX4032-resistant melanoma cells are sensitive to
      novel, next-generation BRAF inhibitors, especially the 'paradox-blocker' PLX8394,
      supporting its use in clinical trials for treatment of melanoma patients with
      BRAF-mutations. 

PMID- 24283592
TI  - The human side of failed hypertension treatment.

PMID- 24283593
TI  - Dietary sodium: a perspective on recent sodium evidence--its interpretation and
      controversies.

PMID- 24283594
TI  - Neglect of several important indexes during the study of human essential
      hypertension.

PMID- 24283595
TI  - Assessment of blood pressure in children: it's all in the details.

PMID- 24283597
TI  - Physician and patient characteristics associated with clinical inertia in blood
      pressure control.
AB  - Clinical inertia, the failure to adjust antihypertensive medications during
      patient visits with uncontrolled hypertension, is thought to be a common problem.
      This retrospective study used 5 years of electronic medical records from a
      multispecialty group practice to examine the association between physician and
      patient characteristics and clinical inertia. Hierarchical linear models (HLMs)
      were used to examine (1) differences in physician and patient characteristics
      among patients with and without clinical inertia, and (2) the association between
      clinical inertia and future uncontrolled hypertension. Overall, 66% of patients
      experienced clinical inertia. Clinical inertia was associated with one physician
      characteristic, patient volume (odds ratio [OR]=0.998). However, clinical inertia
      was associated with multiple patient characteristics, including patient age
      (OR=1.021), commercial insurance (OR=0.804), and obesity (OR=1.805). Finally,
      patients with clinical inertia had 2.9 times the odds of uncontrolled
      hypertension at their final visit in the study period. These findings may aid the
      design of interventions to reduce clinical inertia. 

PMID- 24283596
TI  - The prevalence of primary pediatric prehypertension and hypertension in a real
      world managed care system.
AB  - To assess the burden associated with hypertension, reliable estimates for the
      prevalence of pediatric hypertension are vital. For this cross-sectional study of
      237,248 youths aged 6 to 17 years without indication of secondary hypertension,
      blood pressure (BP) was classified according to age, sex, and height using
      standards from the Fourth Report on the Diagnosis, Evaluation, and Treatment of
      High Blood Pressure in Children and Adolescents as prehypertension with at least
      1 BP >=90th percentile and as hypertension with 3 BPs >=95th percentile. The
      prevalence of prehypertension and hypertension were 31.4% and 2.1%, respectively.
      An additional 21.4% had either 1 (16.6%) or 2 (4.8%) BPs >=95th percentile. Based
      on this large population-based study using routinely measured BP from clinical
      care, a remarkable proportion of youth (6.9%) has hypertension or nearly meets
      the definition of hypertension with 2 documented BPs in the hypertensive range. 

PMID- 24283599
TI  - Impressive blood pressure and heart rate response after percutaneous renal
      denervation in a woman with morbid obesity and severe drug-resistant
      hypertension.

PMID- 24283598
TI  - Risk of hospitalized gastrointestinal bleeding in persons randomized to diuretic,
      ACE-inhibitor, or calcium-channel blocker in ALLHAT.
AB  - Calcium channel blockers (CCBs) are an important class of medication useful in
      the treatment of hypertension. Several observational studies have suggested an
      association between CCB therapy and gastrointestinal (GI) hemorrhage. Using
      administrative databases, the authors re-examined in a post-hoc analysis whether
      the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) participants randomized to the CCB amlodipine had a greater risk of
      hospitalized GI bleeding (a prespecified outcome) compared with those randomized
      to the diuretic chlorthalidone or the angiotensin-converting enzyme inhibitor
      lisinopril. Participants randomized to chlorthalidone did not have a reduced risk
      for GI bleeding hospitalizations compared with participants randomized to
      amlodipine (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.92-1.28).
      Those randomized to lisinopril were at increased risk of GI bleeding compared
      with those randomized to chlorthalidone (HR, 1.16; 95% CI, 1.00-1.36). In a post
      hoc comparison, participants assigned to lisinopril therapy had a higher risk of
      hospitalized GI hemorrhage (HR, 1.27; 95% CI, 1.06-1.51) vs those assigned to
      amlodipine. In-study use of atenolol prior to first GI hemorrhage was related to
      a lower incidence of GI bleeding (HR, 0.69; 95% CI, 0.57-0.83). Hypertensive
      patients on amlodipine do not have an increased risk of GI bleeding
      hospitalizations compared with those taking either chlorthalidone or lisinopril. 

PMID- 24283600
TI  - Screening for obstructive sleep apnea syndrome in hypertensive outpatients:
      clinical characteristics of hypertension are important for their analysis.

PMID- 24283601
TI  - Screening for obstructive sleep apnea in hypertensive outpatients: reply to
      Kawada.

PMID- 24283602
TI  - Tuning the photonic stop bands of nanoporous anodic alumina-based distributed
      bragg reflectors by pore widening.
AB  - A distributed Bragg reflector based on nanoporous anodic alumina was fabricated
      using an innovative cyclic anodization voltage approach, which resulted in an in
      depth modulation of the pore geometry and the refractive index. The effect of a
      pore-widening wet-etching step on the structure's photonic stop-band properties
      was studied. From transmittance measurements, it was shown that by changing the
      pore-widening time it is possible to modulate the photonic stop band in the range
      of visible to near infrared. With the help of a theoretical model, we were able
      to obtain information about the evolution with the pore widening of the material
      effective refractive indexes. This opens the possibility of obtaining several
      optoelectronic devices based on nanoporous anodic alumina. 

PMID- 24283604
TI  - Current and future evidence-based acne treatment: a review.
AB  - INTRODUCTION: Current acne treatment guidelines, as well as, treatment efficacy,
      safety, tolerability and patient preferences must all be considered in
      determining appropriate treatment regimes. Literature can assist physicians'
      evidence-based recommendations according to these factors. AREAS COVERED: To
      determine the current and future direction of pharmacotherapy for treatment of
      acne, a PubMed search was conducted to identify all clinical trials involving the
      treatment of acne from 2009 to 2012. A total of 65 publications met inclusion
      criteria and were reviewed. Literature was heavily focused on the efficacy and
      tolerability of topical combination therapies and supported their use compared
      with monotherapy. A few studies on topical antiandrogens and antioxidants showed
      an alternative approach to targeting acne. Studies on oral monotherapy provided
      some evidence for the use of pulsed azithromycin for acne in adolescents.
      Literature also supports the use of low-dose isotretinoin for moderate acne,
      which was comparable in efficacy to high-dose regimes and better tolerated.
      EXPERT OPINION: Combination acne therapy, whether it be combination topical
      therapy or combination oral and topical therapy, is well supported by recent
      studies. Given the multifactorial pathogenesis of acne and the hurdles of
      adherence to treatment, we anticipate greater development of and reliance on
      combination acne products in the future.

PMID- 24283603
TI  - Correlation of bevacizumab-induced hypertension and outcomes of metastatic
      colorectal cancer patients treated with bevacizumab: a systematic review and meta
      analysis.
AB  - BACKGROUND: With the wide application of targeted drug therapies, the relevance
      of prognostic and predictive markers in patient selection has become increasingly
      important. Bevacizumab is commonly used in combination with chemotherapy in the
      treatment of metastatic colorectal cancer. However, there are currently no
      predictive or prognostic biomarkers for bevacizumab. Several clinical studies
      have evaluated bevacizumab-induced hypertension in patients with metastatic
      colorectal cancer. This meta-analysis was performed to better determine the
      association of bevacizumab-induced hypertension with outcome in patients with
      metastatic colorectal cancer, and to assess whether bevacizumab-induced
      hypertension can be used as a prognostic factor in these patients. METHODS: We
      performed a systematic review and meta-analysis on seven published studies to
      investigate the relationship between hypertension and outcome of patients with
      metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was
      progression-free survival (PFS). Secondary endpoints were overall survival (OS)
      and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were
      extracted from each trial, and the log of the relative risk ratio (RR) was
      estimated for ORR. RESULTS: The occurrence of bevacizumab-induced hypertension in
      patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46
      0.72; P <0.001), OS (HR = 0.50; 95% CI: 0.37-0.68; P <0.001), and ORR (RR = 1.57,
      95% CI: 1.07-2.30, P <0.05), as compared to patients without hypertension.
      CONCLUSIONS: Bevacizumab-induced hypertension may represent a prognostic factor
      in patients with metastatic colorectal cancer.

PMID- 24283605
TI  - Stroke epidemiology in Europe.
AB  - The information on epidemiology of stroke in Europe comes from mortality
      statistics and incidence studies. The purpose of this paper was to review the
      data on mortality, incidence, case fatality and stroke care in Europe, and to
      discuss geographical and temporal trends, taking into account methodological
      problems. The available updated studies on mortality and incidence were reviewed.
      Considering methodological characteristics, incidence studies were evaluated
      separately for "ideal" and "nonideal" studies. The preliminary data of the
      ongoing EC Stroke Project were also examined. Marked differences are observed in
      mortality rates across European countries. Rates are higher in Eastern compared
      to Western countries. Temporal trends are decreasing in Western and increasing in
      Eastern countries. Incidence data are scanty and probably not fully
      representative. Preliminary observations show that marked differences exist in
      stroke care across different countries. Geographical and temporal trends in
      mortality and morbidity may reflect both methodological inhomogeneity and
      differences in prevalence of risk factors, incidence and survival. Differences in
      socio-economical level may have an impact on stroke care, and may indirectly
      influence stroke frequency measures. A collaborative effort is needed for
      standardizing the methodologies, checking the reliability of data, and examining
      more extensively trends in risk factors and stroke care. This may make it
      possible to optimize the cost effectiveness of management of stroke patients in
      Europe. 

PMID- 24283606
TI  - Clues about the functional neuroanatomy of verbal working memory: a study of
      resting brain glucose metabolism in Parkinson's disease.
AB  - In addition to motor impairment, non-demented patients with Parkinson's disease
      (PD) exhibit a variable degree of cognitive impairment which could indicate
      dysfunction in the central executive of working memory. In this study, we have
      employed positron emission tomography measurements of resting brain glucose
      metabolism (CMRglc) to investigate the neural substrates underlying this
      dysfunction, taking PD as a model disease to assess, within the framework of
      Alexander's striato-pallido-thalamo-cortical cognitive circuits the functional
      neuroanatomy of the central executive. We studied central executive performance
      in 17 non-demented, highly selected PD patients, by means of the Brown-Peterson
      paradigm (BPP), and correlated the BPP performance according to various response
      delays (from 0 to 18 s) with local cerebral metabolic rates of glucose. We
      document for the first time that the BPP performance in PD is heterogeneous not
      only across delays (with PD patients selectively impaired for the 0 and 3 s
      delays, compatible with impaired attention and central executive, respectively),
      but also from subject to subject; a multiple correspondence analysis was able to
      distinguish two patient subgroups according to short delay BPP performance. The
      correlational analysis with PET data evidenced a limited number of significant
      correlations, most of which were consistent with our working hypothesis. Notably,
      a positive correlation between lateral frontal relative metabolism and BPP
      performance for short delays, and a negative one between these scores and
      mediodorsal (MD) thalamic nucleus metabolism, would fit the way in which caudate
      dopamine denervation would alter in opposite directions frontal cortex and MD
      nucleus synaptic activity and in turn affect central executive function. The
      results from this study lend further support to the role of altered thalamo
      prefrontal interplay as the basis for central executive dysfunction in PD. 

PMID- 24283607
TI  - Isoflurane for 7 days in refractory status epilepticus.
AB  - There is limited experience with continuous (>3 days) isoflurane anesthesia for
      status epilepticus (SE). We present a case with prolonged SE, probably due to
      thallium intoxication, in which isoflurane successfully suppressed seizure
      activity over 7 days without adverse effects. When isoflurane was discontinued,
      seizures returned despite high doses of barbiturates, and the patient died
      several months later. Early isoflurane anesthesia is an effective alternative
      therapy in prolonged convulsive SE resistant to common therapy and intravenous
      general anesthesia. However, its continuous application for several days requires
      familiarity with anesthesiologic principles, and scavenging of expiratory air. 

PMID- 24283608
TI  - Carbamazepine and phenytoin: combination versus single drug therapy.
AB  - The records of 18 patients with intractable partial seizures who were observed on
      an in-patient epilepsy unit during single drug treatment with carbamezepine (CBZ)
      or phenytoin (PHT) and during combination therapy with both drugs were evaluated
      retrospectively. Seizure frequency was significantly lower during combination
      therapy (p < 0.01) and toxicity, as measured by an eight point objective scale,
      did not increase significantly (p > 0.10). In addition subjective signs of
      clinical toiicity (e.g. nausea, ataxia, etc.) increased only slightly during
      combination versus monotherapy. These findings were consistently seen whether the
      data were evaluated in total (i.e. treatment periods at least 7 weeks) or
      evaluated by using standardized 35 day treatment periods. In the absence of a
      blinded clinical trial evaluating PHT/CBZ combination, these findings support
      consideration of this combination in Intractable patients who have failed
      rigorously administered mono-therapy trials, recognizing however that only a
      small percentage of patients will improve on combination therapy. 

PMID- 24283609
TI  - Peripheral iron metabolism in patients with focal cerebral ischemia.
AB  - To ascertain the possible role of iron as a risk factor for cerebral ischemia, we
      studied the serum levels of iron, transferrin and ferritin in 42 patients between
      the third and seventh days after a cerebral ischemic event (transient ischemic
      attack, reversible ischemic neurological deficit or cerebral infarction) and in
      62 matched controls. The serum levels of iron did not differ significantly
      between cerebral ischemic patient and control groups. Serum transferrin levels
      were lower and ferritin higher in stroke patients than in controls. These values
      were not influenced by age, blood pressure, or smoking and alcohol drinking
      habits. These results suggest that iron stores could be related to the risk for
      cerebral ischemia. 

PMID- 24283610
TI  - Decreased serum selenium concentrations in patients with Parkinson's disease.
AB  - Selenium is an essential component of the antioxidant enzyme glutathione
      peroxidase. The activity of this enzyme is reduced in the substantia nigra of
      patients with Parkinson's disease (PD), but the results of studies on
      erythrocytes are controversial. We compared the serum levels of selenium and the
      24 h urinary selenium excretion (measured by hydride generation atomic absorption
      spectrophotometry) in 29 PD patients and 30 matched controls. Serum selenium
      levels were significantly lower in PD patients than in controls (34.6 +/- 2.35
      and 45.2 +/- 3.83 MUg/l, p < 0.05) while urinary excretion was similar for both
      groups (47.1 +/- 6.25 and 45.5 +/- 5.38 MUg/24 h). These values were not
      influenced by antiparkinsonian drugs, and they did not correlate with age, age at
      onset and duration of the PD, scores of the Unified PD Rating Scale or the Hoehn
      and Yahr staging in the PD group. These results might suggest a possible role of
      low serum selenium levels in the risk for, or a consequence of the oxidative
      stress in PD. 

PMID- 24283611
TI  - Potentiation instead of habituation characterizes visual evoked potentials in
      migraine patients between attacks.
AB  - We have studied habituation of the pattern-reversal visual evoked potential (VEP)
      in healthy volunteers (n = 16) and in patients suffering from migraine without (n
      = 27) or with aura (n = 9). Five blocks of 50 responses at a stimulation rate of
      3.1 Hz were sequentially averaged and analyzed separately for latencies, peak-to
      peak amplitudes of N1-P1 and P1-N2, and the area under the N2 component Latencies
      of N1, P1, or N2 components were not significantly different between the
      sequential trial blocks, or between groups. Mean amplitudes of N1-P1 and P1-N2 in
      the first and subsequent blocks of SO responses were not statistically different
      among groups. In healthy subjects, there was a decrement of N1-P1 and P1-N2
      amplitudes and N2 area on successive averagings. This habituation was maximal in
      the third and fourth blocks, but tended to disappear in the fifth block. In
      marked contrast to healthy subjects, migraine patients were characterized by a
      transient amplitude increment (i.e. potentiation) of VEP components which reached
      its maximum in the second to fourth blocks. Amplitude changes in sequential
      blocks were not dependent on attention and differed significantly between healthy
      subjects and migraineurs, but not between migraine with and without aura. Taken
      together with previous studies showing deficient habituation of contingent
      negative variation in migraine, these results indicate a dysfunction of central
      information processing which might have behavioral and pathogenic correlates. 

PMID- 24283612
TI  - Efficacy of antibiotics in neurobrucellosis.
AB  - Brucellosis is a systemic infection that rarely involves the nervous system. This
      paper describes 21 cases of neurobrucellosis affecting different parts of the
      peripheral and central nervous system. The various presentations closely
      simulated acute meningoencephalitis, myelitis, cerebral ischaemia, radiculopathy
      or multisystem degeneration. All patients received adequate combined
      antimicrobial therapy of trimethroprim-sulfamethoxazole, doxycycline, and/or
      rifampicin. The improvement was quick and complete in meningoencephalitic
      patients, while others with structural changes in the nervous system did not
      recover and ended up with permanent deficits. The combination regimen and
      duration of therapy are the focus of this study. 

PMID- 24283613
TI  - Low dose bromocriptine-induced pleural effusion and pleuropulmonary fibrosis.
AB  - We describe a parkinsonian patient who developed a slight asymptomatic pleural
      effusion during prolonged therapy with low dose bromocriptine (BCR) in addition
      to levodopa, following prior treatment with CQA 206-291. A moderate increase of
      BCR dosage prompted a severe pleuropulmonary inflammatory reaction with
      polyclonal activation and elevated serum liver enzymes, which normalized
      following withdrawal of the drug. The clinical syndrome and close relation to BCR
      treatment are in keeping with a diagnosis of BCR-related pleuropulmonary fibrosis
      (PPF). Features of this case are compared with previous reports on dopamine (DA)
      agonist-related PPF. This case supports earlier suggestions of polyclonal
      activation in DA agonist-related PPF and suggests hepatic involvement and dose
      dependency. 

PMID- 24283614
TI  - Evoked potentials in mitochondrial disorders.
AB  - Twenty-eight adult patients with mitochondrial disease were evaluated with
      muitimodal evoked potentials (EPs) to assess a possible CNS involvement The
      patients were classified into five groups: encephalopathy (two cases),
      progressive external ophthalmoplegia (PEO; four cases), pure myopatby (15 cases),
      cardiomyopathy (five cases) and asymptomatic relatives (two cases). EPs showed
      differences between encephalopathy (all EP modalities affected) and PEO groups
      (all patients with at least one EP altered), with lesser degrees of affection in
      pure myopathy and cardiomyopathy groups. The asymptomatics registered normal EPs.
      In view of these results, progressive CNS damage in mitochondriopathies,
      expressed by abnormal EPs, can be established as follows (from greatest to minor
      severity): encephalopathy, PEO, pure myopathy/cardiomyopathy and asymptomatic
      condition. 

PMID- 24283615
TI  - Natural interferon-beta in chronic progressive multiple sclerosis: results after
      2 years of treatment and 2 years of follow up.
AB  - Seventeen chronic progressive multiple sclerosis patients were treated with
      natural interferon-beta (IFN-beta) for 2 years, thereafter they were followed up
      for 2 years. IFN-beta was given 1 million IU/day i.m. for 1 week, then 3 million
      IU daily for 3 weeks followed by a maintenance regimen of 2 million IU twice a
      week for 23 months. Kurtzke Expanded Disability Status Scale score was 5.5 at
      entry and did not change at the end of the first year. It increased to 5.8 at the
      end of the second year and to 6.5 at the end of the follow-up. Three patients
      worsened after 1 year, six after 2 years and nine at the end of the follow-up.
      Brain MRI was performed at entry and after 1 year: mean lesion score increased by
      13.4%. MRI changes were not correlated with clinical course. Natural IFN-beta
      seemed to have some beneficial effect when high doses were given: this effect
      tended to disappear after IFN-beta was reduced, followed by a more severe disease
      progression after its withdrawal. 

PMID- 24283616
TI  - Oromandibular dystonia associated with fluoxetine.
AB  - A 66 year old patient with major depression treated with fluoxetine developed
      persistent oromandibular dystonia and mild akathisia. She improved significantly
      after discontinuation of the drug and treatment with biperiden. The temporal
      relationship between the use of fluoxetine and the occurrence of dystonia and
      akathisia suggests that fluoxetine may have induced tardive dystonia in this
      patient possibly due to a serotonergically mediated inhibition of striatal
      dopaminergic neurotransmission. We believe that this is the first reported case
      of persistent or tardive dystonia associated with fluoxetine treatment. 

PMID- 24283617
TI  - Synthesis, crystal structure, and high temperature transport properties of p-type
      Cu2Zn(1-x)Fe(x)SnSe4.
AB  - Iron substituted Cu2Zn(1-x)Fe(x)SnSe4 stannites were synthesized by reaction of
      the constituent elements and subsequent annealing, followed by densification by
      hot-pressing. The compositions for each specimen were confirmed with a
      combination of Rietveld refinement and elemental analysis. Refinement results
      indicated that only the 2a site was occupied by Zn and Fe. High temperature
      transport properties were measured from 300 to 800 K. The electrical resistivity
      and thermal conductivity decrease with increasing Fe content. For the lower Fe
      content specimens with x = 0.2 and 0.4, the electrical properties are strongly
      temperature dependent, unlike that of the higher Fe content specimens (x = 0.6
      and 0.8). A maximum ZT value of 0.46 was obtained at 800 K for
      Cu2Zn0.4Fe0.6SnSe4.

PMID- 24283618
TI  - Penetrating orbit injury: challenge to emergency medicine.
AB  - BACKGROUND: Penetrating orbital injuries pose a serious threat to vision, ocular
      motility, and in some cases, life. The setting and causes of eye injury are
      diverse, but previous studies have demonstrated that the risk and type of injury
      is often correlated with age, gender, and race. Pediatric ocular injury is often
      accidental and may be preventable. A focused history and prompt ocular
      examination are essential to immediate management. CASE PRESENTATION: This
      article describes a case of protruding foreign body-related penetrating orbit
      injury with a retained foreign body in a 4-year-old male from a town in the
      eastern part of Nepal. The child presented to the emergency with foreign body in
      situ without receiving any pre emergency care without any medical attendance. The
      patient was managed with non-operative removal of foreign body in the emergency.
      The case discussion will review the initial presentation, examination, resultant
      management decisions, and final outcome. CONCLUSION: Foreign body presentations
      may be diverse and non-operative management may be considered in selected cases.
      Resource availability and conditions at presentations may also influence the
      management decisions. This case presentation has described such a scenario in
      developing country like Nepal and is expected to be interest across various
      medical specialties.

PMID- 24283619
TI  - Long-term treatment with oral propranolol reduces relapses of infantile
      hemangiomas.
AB  - Oral propranolol (OP) has been shown to be effective in the treatment of
      complicated infantile hemangiomas (IHs), but optimal treatment duration to avoid
      relapses after stopping OP treatment has not been established. The objective of
      this study was to compare the frequency of relapses in long-term OP treatment
      with that of short-term OP treatment. This was a retrospective cohort study of 30
      patients with complicated IHs who received treatment with OP. Patients were
      divided into two groups: OP treatment of 8 months or less and OP treatment of
      longer than 8 months. OP was started at 1 mg/kg/day in three doses every 8 hours
      for 1 week and increased to 1.5 to 4 mg/kg/day afterward. Ultrasound was used to
      objectively measure the response to treatment. Clinical and ultrasound assessment
      showed a decrease in IH size and resolution of complications in all patients (n =
      30). In the short-term group (n = 10), nine patients (90%) relapsed after
      stopping treatment. In the long-term group (n = 20), the duration of treatment
      was 12 months in all patients, and only 1 patient out of the 20 treated (5%)
      showed relapse 2 months after finishing the full treatment (odds ratio = 18, 95%
      confidence interval 2.6, 123, p < 0.001. Twelve months of treatment of IH with OP
      is associated with a significantly lower rate of relapse than with shorter
      treatment.

PMID- 24283621
TI  - Peniciketals A-C, new spiroketals from saline soil derived Penicillium
      raistrichii.
AB  - Peniciketals A-C (1-3), three new spiroketals with a benzo-fused 2,8
      dioxabicyclo[3.3.1]nonane moiety, were isolated from the saline soil derived
      fungus Penicillium raistrichii. Their structures including absolute
      configurations were established by NMR, X-ray diffraction, and ECD calculations.
      Their cytotoxicities were tested against A549, HL-60, and K562 cell lines, and 1
      3 showed the selective effects on HL-60 cells with IC50 values of 3.2, 6.7, and
      4.5 MUM, respectively. 

PMID- 24283620
TI  - Luteinizing hormone and human chorionic gonadotropin: distinguishing unique
      physiologic roles.
AB  - Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are integral
      components of the hypothalamic-pituitary-gonadal axis, which controls sexual
      maturation and functionality. In the absence of signaling through their shared
      receptor, fetal sexual differentiation and post-natal development cannot proceed
      normally. Although they share a high degree of homology, the physiologic roles of
      these hormones are unique, governed by differences in expression pattern,
      biopotency and regulation. Whereas LH is a key regulator of gonadal
      steroidogenesis and ovulation, hCG is predominantly active in pregnancy and fetal
      development. Emerging evidence has revealed endogenous functions not previously
      ascribed to hCG, including participation in ovulation and fertilization,
      implantation, placentation and other activities in support of successful
      pregnancy. Spontaneous and induced mutations in LH, hCG and their mutual receptor
      have contributed substantially to our understanding of reproductive development
      and function. The lack of naturally occurring, functionally significant mutations
      in the beta-subunit of hCG reinforce its putative role in establishment of
      pregnancy. Rescue of reproductive abnormalities resulting from aberrant
      gonadotropin signaling is possible in certain clinical contexts, depending on the
      nature of the underlying defect. By understanding the physiologic roles of LH and
      hCG in normal and pathologic states, we may better harness their diagnostic,
      prognostic and therapeutic potential.

PMID- 24283622
TI  - Post-synthetic modification of metal-organic framework thin films using click
      chemistry: the importance of strained C-C triple bonds.
AB  - In this work, we demonstrate that strain-promoted azide-alkyne cycloaddition
      (SPAAC) yields virtually complete conversion in the context of the post-synthetic
      modification (PSM) of metal-organic frameworks (MOFs). We use surface-anchored
      MOF (SURMOF) thin films, [Zn2(N3-bdc)2(dabco)], grown on modified Au substrates
      using liquid-phase epitaxy (LPE) as a model system to first show that, with
      standard click chemistry, presently, the most popular method for rendering
      additional functionality to MOFs via PSM, quantitative conversion yields, cannot
      be reached. In addition, it is virtually impossible to avoid contaminations of
      the product by the cytotoxic Cu(I) ions used as a catalyst, a substantial problem
      for applications in life sciences. Both problems could be overcome by SPAAC,
      where a metal catalyst is not needed. After optimization of reaction conditions,
      conversion yields of nearly 100% could be achieved. The consequences of these
      results for various applications of PSM-modified SURMOFs in the fields of
      membranes, optical coatings, catalysis, selective gas separation, and chemical
      sensing are briefly discussed. 

PMID- 24283623
TI  - Living donor liver transplantation for pediatric patients with metabolic
      disorders: the Japanese multicenter registry.
AB  - LDLT is indicated for a variety of metabolic disorders, primarily in Asian
      countries due to the absolute scarcity of deceased donor LT. We analyzed data for
      all pediatric LDLTs performed between November 1989 and December 2010, during
      which 2224 pediatric patients underwent LDLT in Japan. Of these patients, 194
      (8.7%) underwent LDLT for metabolic disorders. Wilson's disease (n = 59; 30.4%)
      was the most common indication in the patients with metabolic disorders, followed
      by OTCD (n = 40; 20.6%), MMA (n = 20; 10.3%), and GSD (n = 15; 7.7%). The one-,
      five-, 10-, and 15-yr patient and graft survival rates were 91.2%, 87.9%, 87.0%,
      and 79.3%, and 91.2%, 87.9%, 86.1%, and 74.4%, respectively. Wilson's disease and
      urea cycle deficiency were associated with better patient survival. The use of
      heterozygous donors demonstrated no negative impact on either the donors or
      recipients. With regard to X-linked OTCD, symptomatic heterozygote maternal
      donors should not be considered potential donor candidates. Improving the
      understanding of the long-term suitability of this treatment modality will
      require the registration and ongoing evaluation of all patients with inherited
      metabolic disease considered for LT.

PMID- 24283625
TI  - Use of transoral endoscopy for pharyngeal examination: cross-sectional analysis.
AB  - BACKGROUND AND AIM: Transoral endoscopy with narrow band imaging (NBI) is useful
      for identifying early-stage head and neck cancer. However, the screening
      capability of transoral upper gastrointestinal endoscopy has not yet been
      systematically evaluated. We evaluated the usefulness of transoral upper
      gastrointestinal endoscopy for pharyngeal examination. METHODS: This cross
      sectional study evaluated 480 patients. All endoscopic pharyngeal examinations
      with NBI were carried out in accordance with prescribed procedures, consisting of
      10 images each and all images were assessed by a blinded reviewer. We examined
      the association between the diagnostic usefulness of pharyngeal examination and
      other factors. RESULTS: Median subject age was 64 years (range 22-90 years), and
      64% were male. Almost all patients (98%) had an Eastern Cooperative Oncology
      Group Performance Status of 0 or 1.Butylscopolamine bromide was given to 382
      patients (80%), and a sedative was given to 460 (96%) patients. Median
      observation time was 74 s (range, 16-362 s), resulting in a mean of 9.0 usable
      images per patient. However, photographs of the right and left pyriform sinuses
      were consistently poor. Ordered logistic regression analysis showed that quality
      images were positively correlated with increased patient age. CONCLUSIONS:
      Transoral endoscopic examination was possible in most patients for screening of
      the head and neck. However, results were poor in the pyriform sinuses, indicating
      that additional improvements of examination methods and instruments are needed to
      enhance screening accuracy.

PMID- 24283626
TI  - Socioenvironmental threats to pastoral livelihoods: risk perceptions in the Altay
      and Tianshan Mountains of Xinjiang, China.
AB  - Subjective risk perceptions give rise to unique policy implications as they
      reflect both the expectation of risk exposure and the ability to mitigate or cope
      with the adverse impacts. Based on data collected from semistructured interviews
      and iterative ranking exercises with 159 households in the Altay and Tianshan
      Mountains of Xinjiang, China, this study investigates and explains the risks with
      respect to a seriously understudied population and location. Using both
      geostatistical and econometric methods, we show that although fear of
      environmental crisis is prevalent among our respondents, recently implemented
      pastoral conservation, sedentarization, and development projects are more likely
      to be ranked as the top concerns among affected households. In order to reduce
      these concerns, future pastoral policy must be built on the livestock economy,
      and intervention priority should be given to the geographic areas identified as
      risk hot spots. In cases where pastoralists have to give up their pastures, the
      transition to other comparable livelihood strategies must be enabled by creating
      new opportunities and training pastoralists to acquire the needed skills. 

PMID- 24283627
TI  - Evaluating summary statistics used to test for incomplete lineage sorting: mito
      nuclear discordance in the reef sponge Callyspongia vaginalis.
AB  - Conflicting patterns of population differentiation between the mitochondrial and
      nuclear genomes (mito-nuclear discordance) have become increasingly evident as
      multilocus data sets have become easier to generate. Incomplete lineage sorting
      (ILS) of nucDNA is often implicated as the cause of such discordance, stemming
      from the large effective population size of nucDNA relative to mtDNA. However,
      selection, sex-biased dispersal and historical demography can also lead to mito
      nuclear discordance. Here, we compare patterns of genetic diversity and
      subdivision for six nuclear protein-coding gene regions to those for mtDNA in a
      common Caribbean coral reef sponge, Callyspongia vaginalis, along the Florida
      reef tract. We also evaluated a suite of summary statistics to determine which
      are effective metrics for comparing empirical and simulated data when testing
      drivers of mito-nuclear discordance in a statistical framework. While earlier
      work revealed three divergent and geographically subdivided mtDNACOI haplotypes
      separated by 2.4% sequence divergence, nuclear alleles were admixed with respect
      to mitochondrial clade and geography. Bayesian analysis showed that substitution
      rates for the nuclear loci were up to 7 times faster than for mitochondrial COI.
      Coalescent simulations and neutrality tests suggested that mito-nuclear
      discordance in C. vaginalis is not the result of ILS in the nucDNA or selection
      on the mtDNA but is more likely caused by changes in population size. Sperm
      mediated gene flow may also influence patterns of population subdivision in the
      nucDNA.

PMID- 24283628
TI  - The effects of divided attention on encoding processes under incidental and
      intentional learning instructions: underlying mechanisms?
AB  - Divided attention (DA) at encoding has been shown to significantly disrupt later
      memory for the studied information. However, what type of processing gets
      disrupted during DA remains unresolved. In this study, we assessed the degree to
      which strategic effortful processes are affected under DA by comparing the
      effects of DA at encoding under intentional and pure incidental learning
      instructions. In three experiments, participants studied list of words or word
      pairs under either full or divided attention. Results of three experiments, which
      used different methodologies, converged to show that the effects of DA at
      encoding reduce memory performance to the same degree under incidental and
      intentional learning. Secondary task performance indicated that encoding under
      intentional learning instructions was more effortful than under incidental
      learning instructions. In addition, the results indicated enhanced attention to
      the initial appearance of the words under both types of learning instructions.
      Results are interpreted to imply that other processes, rather than only strategic
      effortful ones, might be affected by DA at encoding. 

PMID- 24283629
TI  - Atomic layer deposition-derived ultra-low-density composite bulk materials with
      deterministic density and composition.
AB  - A universal approach for on-demand development of monolithic metal oxide
      composite bulk materials with air-like densities (<5 mg/cm(3)) is reported. The
      materials are fabricated by atomic layer deposition of titania (TiO2) or zinc
      oxide (ZnO) using the nanoscale architecture of 1 mg/cm(3) SiO2 aerogels formed
      by self-organization as a blueprint. This approach provides deterministic control
      over density and composition without affecting the nanoscale architecture of the
      composite material that is otherwise very difficult to achieve. We found that
      these materials provide laser-to-X-ray conversion efficiencies of up to 5.3%,
      which is the highest conversion efficiency yet obtained from any foam-based
      target, thus opening the door to a new generation of highly efficient laser
      induced nanosecond scale multi-keV X-ray sources. 

PMID- 24283630
TI  - 'TWIST and switch' metastasis.

PMID- 24283631
TI  - The neurology of autism: many unanswered questions.
AB  - Autism is a behaviorally defined developmental disorder of the brain almost
      always presenting in infancy or the preschool years. Its symptoms persist life
      long, although partial compensation is possible through targeted special
      education that addresses children's deficits in sociability, verbal and non
      verbal communication, and atypical range of interests, activities, and cognitive
      skills. Although a majority of autistic individuals are mentally deficient, IQ is
      not a defining feature and verbal autistic persons of normal intelligence are
      increasingly being identified, referred to as Asperger syndrome. Meager
      neuropathologic data have disclosed subtle prenatal cellular limbic and
      cerebellar abnormalities. Autism is associated with a variety of defined genetic
      and acquired conditions, with multifactorial genetic traits, alone or interacting
      with environmental events, presumably responsible for most unexplained cases.
      Autistic regression is frequent and poorly understood and may be associated with
      clinical or subclinical epilepsy. Unravelling the neurobiologic basis of a
      disorder that may affect 1-2 in 1000 children will require a concerted
      multidisciplinary attack. 

PMID- 24283624
TI  - Transient receptor potential ion channels in primary sensory neurons as targets
      for novel analgesics.
AB  - The last decade has witnessed an explosion in novel findings relating to the
      molecules involved in mediating the sensation of pain in humans. Transient
      receptor potential (TRP) ion channels emerged as the greatest group of molecules
      involved in the transduction of various physical stimuli into neuronal signals in
      primary sensory neurons, as well as, in the development of pain. Here, we review
      the role of TRP ion channels in primary sensory neurons in the development of
      pain associated with peripheral pathologies and possible strategies to translate
      preclinical data into the development of effective new analgesics. Based on
      available evidence, we argue that nociception-related TRP channels on primary
      sensory neurons provide highly valuable targets for the development of novel
      analgesics and that, in order to reduce possible undesirable side effects, novel
      analgesics should prevent the translocation from the cytoplasm to the cell
      membrane and the sensitization of the channels rather than blocking the channel
      pore or binding sites for exogenous or endogenous activators.

PMID- 24283632
TI  - Central defects of autonomic function in secondary progressive multiple
      sclerosis: observations based on cardiovascular and growth hormone responses to
      clonidine.
AB  - The haemodynamic, autonomic and hormonal effects of the centrally acting
      sympatholytic drug clonidine have been studied in 10 patients with secondary
      progressive multiple sclerosis (MS) and 10 age- and sex-matched normal subjects
      (controls). Detailed physiological studies, previously described in these 10 MS
      patients, indicated that none had postural hypotension or an abnormal Valsalva
      manoeuvre; six, however, had impaired responses to a range of pressor tests,
      suggestive of a central autonomic abnormality. In the controls after clonidine,
      there was a fall in blood pressure and superior mesenteric artery vascular
      resistance. Finger temperature and growth hormone levels rose. In the MS patients
      after clonidine, the haemodynamic responses varied. In five out of ten MS
      patients, as in the controls, there was a fall in blood pressure and superior
      mesenteric vascular resistance, while finger temperature rose. There was no
      haemodynamic response to clonidine in the other five MS patients. In eight out of
      ten MS patients there was no rise in plasma growth hormone levels after
      clonidine. The abnormal haemodynamic responses to clonidine, taken in conjunction
      with the previous physiological studies, suggest involvement of central
      sympathetic interconnections in five of the MS patients, probably as part of the
      demyelinating process. The impaired growth hormone response to clonidine occurred
      in a greater number of patients and may indicate lesions in the hypothalamus.
      These observations in MS patients, without overt clinical evidence of autonomic
      failure, indicate that the haemodynamic and growth hormone responses to clonidine
      may be an early indicator of autonomic dysfunction involving central autonomic
      centres and pathways. 

PMID- 24283634
TI  - The role of tumour necrosis factor alpha in the pathogenesis of multiple
      sclerosis, and pentoxifylline as a possible pharmacotherapeutic intervention.

PMID- 24283633
TI  - Neuropsychological status of mitochondrial encephalomyopathies.
AB  - We studied 15 patients suffering from mitochondrial encephalomyopathies (MEM) by
      a neuropsychological screening procedure. Eight of the patients were diagnosed as
      having progressive external ophthalmoplegia (PEO), four mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and three
      Kearns-Sayre syndrome (KSS). Based on test results covering memory, orientation,
      non-verbal intelligence, drawing, arithmetics, word list generation, trail making
      and digit span, only four patients were regarded as normal, two in the PEO and
      two in the KSS groups, while five patients were found to be demented (two
      patients in the PEO and three patients in the MELAS groups). Although memory
      problems were very common, it is concluded that no uniform pattern of
      neuropsychological deficits is seen in MEM, that MELAS patients apparently are
      severely handicapped cognitively, and that considerable mental deterioration may
      be seen even with normal computer-assisted tomography findings. 

PMID- 24283635
TI  - Acute posterior multifocal placoid pigment epitheliopathy presenting as an
      aseptic meningitis.
AB  - We report a 33-year-old patient with acute posterior multifocal placoid pigment
      epitheliopathy presenting as steroid-responsive aseptic meningitis. Four unusual
      biological abnormalities were present: an elevated erythrocyte sedimentation
      rate, circulating immunocomplexes, an oligoclonal banding in cerebrospinal fluid
      and a transient abnormal urine sediment All these and the prompt response to
      corticosteroids give support to the hypothesis of a systemic autoimmune disease. 

PMID- 24283636
TI  - Huntington's disease: a multidisciplinary study.
AB  - Huntington's disease (HD) is characterized by the presence of movement disorders,
      cognitive decline and psychiatric disturbances. Recently, the gene responsible
      for HD has been found. As a result, a more direct test for HD is available. This
      may lead to a comprehensive approach to HD, since it is now possible to study HD
      patients without uncertainties in diagnosis. We carried out a clinical-genetic
      study on 45 patients with HD. We performed molecular analysis on 39 patients. All
      had an abnormal expansion of (CAG)n ranging from 41 to 90 triplets (mean 50.8 +/-
      11.5 S.D.). There was a strong inverse correlation between (CAG)n expansion and
      age at onset Gender of the affected parent influenced age at onset (p < 0.001)
      and number of triplets (p < 0.001). A significant impairment of akinesia (p <
      0.001), chorea (p < 0.005), MMSE (p < 0.01) and Rey scores (p < 0.05) occurred
      across successive stages of functional disability. Hooper Visual Organization
      Test (HVOT) scores did not change significantly across stages, but this test was
      extremely useful to discriminate between patients at an early stage and controls.
      A significant correlation was found between functional disability and motor
      cognitive decline; correlation was stronger for motor (akinesia, r = 0.77;
      chorea, r = 0.61) than for cognitive aspects (MMSE, r = - 0.54; Rey, r = - 0.51;
      HVOT, r = -0.35). 

PMID- 24283637
TI  - Apolipoprotein E allelic variants predict dementia in elderly patients with
      memory impairment.
AB  - Apolipoprotein E-E4 (ApoEE4 allele is a major risk factor of late-onset
      Alzheimer's disease (AD). We now report that: (1) this allelic variant is more
      frequent among patients with age-associated memory impairment (AAMI) than among
      healthy control subjects; (2) after a 3 year follow-up, those AAMI patients who
      developed dementia had ApoEE4 more frequently than those who did not; (3) ApoE
      allele distribution did not differ significantly between demented AAMI and late
      onset AD patients. These results suggest that ApoEE4 predicts the development of
      dementia in AAMI patients, and that AAMI, an idiopathic amnesic syndrome of high
      prevalence among the elderly, and late-onset AD are different stages of the same
      disorder. 

PMID- 24283638
TI  - Co-existence of Lambert-Eaton myasthenic syndrome and subacute cerebellar
      degeneration in a patient with rheumatoid arthritis.
AB  - A 38 year old woman with rheumatoid arthritis had a rare co-existence of Lambert
      Eaton myasthenic syndrome and subacute cerebellar degeneration. She had mild but
      transient improvement in muscle power following plasmapheresis, which correlated
      with the degree of increment on high rate repetitive nerve stimulation (RNS). Her
      cerebellar signs did not improve, however. This differential therapeutic response
      may be due to different mechanisms of injury and tissue susceptibility. 

PMID- 24283639
TI  - Impaired water metabolism and cerebral oedema following experimental subarachnoid
      haemorrhage in rats(1.).
AB  - The acute phase of subarachnoid haemorrhage (SAH) is frequently associated with
      an impaired water metabolism and a disposition to cerebral oedema. For study of
      the pathogenesis of brain oedema following SAH, an experimental model of SAH was
      created in the rat The diuretic curves after water loading, the brain water and
      electrolyte contents and the plasma and cerebrospinal fluid arginine vasopressin
      (AVP) levels were examined in rats with SAH. Following a water load, a
      significant water retention and increases in brain water and sodium contents were
      observed after subarachnoid bleeding. Plasma and cerebrospinal fluid AVP levels
      were also elevated following SAH. It can be concluded that AVP plays important
      roles in the development of antidiuresis after water loading and in the
      disturbance of the brain water and electrolyte balance following experimental
      SAH. 

PMID- 24283640
TI  - Neurological involvement in antiphospholipid syndrome: clinical and instrumental
      evaluation in 21 consecutive cases.
AB  - Twenty-one consecutive women with the antiphospholipid syndrome were investigated
      with a full cardiological and neurological examination including a semi
      structured interview. They were also systematically studied with magnetic
      resonance imaging (MRI), transcranial Doppler (TCD), duplex sonography of neck
      vessels and transesophageal echocardiography (TEE). Nearly 67% of patients had
      signs or symptoms suggestive of CNS involvement Migraine-like headache, stroke,
      ocular disorders and epilepsy were the most frequent disturbances. MRI was
      abnormal in 65% of patients who underwent the examination and showed two distinct
      patterns of abnormality: either territorial infarctions or multiple subcortical
      spotty lesions. TCD showed in one case a stenosis affecting the main trunk of the
      middle cerebral artery. TEE demonstrated potentially emboligenic mitral
      vegetations in 72% of patients. These findings suggest that antiphospholipid
      syndrome is burdened with a high rate of complications affecting the CNS, which
      are likely to be mostly thromboembolic. It is possible that both cardiogenic
      embolism and in situ thrombosis of cerebral vessels occur. Given the relative
      absence of conventional vascular risk factors, antiphospholipid antibodies are
      likely to represent a true risk factor for cerebrovascular disease through the
      mechanism of an immunologically mediated hypercoagulable state. 

PMID- 24283641
TI  - Temporal lobe epilepsy with bilateral seizure origin studied by [(18) F]FDG
      positron emission tomography.
AB  - Nine patients who underwent presurgical evaluation because of medically
      refractory temporal lobe epilepsy (TLE) showed either unilateral, although
      alternating in side, or bilateral simultaneous seizure onsets in both temporal
      lobes (TL). EEG recordings with semi-invasive foramen ovale electrodes revealed
      in seven patients a predominance of seizure onset in one TL of between 50% and
      88%. In two patients the majority of seizures originated simultaneously in both
      TL. In four patients a unilateral selective amygdalohippocampectomy resulted in a
      good to excellent seizure outcome without noteworthy memory deficits and
      confirmed the preoperative lateralization of the primary epileptogenic focus by
      interictal (18) F-fluorodeoxyglucose positron emission tomography (PET). Five
      patients were rejected from surgery due to strong bilaterality of their epilepsy
      and/or divergent presurgical findings. PET contributed to the decision of whether
      surgery should be performed: all patients who underwent surgery had a unilateral
      TL hypometabolism which was concordant with the findings of other tests. Patients
      in whom surgery was denied had either bilateral temporal hypometabolism or the
      PET findings were discordant with other results obtained during the presurgical
      evaluation. 

PMID- 24283642
TI  - Invasion of a subcutaneous Aspergillus abscess into the brain.
AB  - We present the case of a 57 year old woman with contiguous infection by
      Aspergillus fumigatus. The lesion started subcutaneously, forming an abscess.
      Seventeen days later we observed an intracranial abscess, infection of the
      frontal sinus and destruction of the frontal bone between the subcutaneous
      abscess and the sinus. 

PMID- 24283643
TI  - Neuralgic amyotrophy and infectious mononucleosis: a case report.
AB  - A 27 year old man developed neuralgic amyotrophy of the right upper limb 5 weeks
      after an acute febrile illness which was proven serologically to be caused by
      Ebstein-Barr virus. The weakness developed in a limb that had been used to
      perform heavy manual labour. A parallel with a similar phenomenon described in
      association with paralytic poliomyelitis is noted.- 

PMID- 24283644
TI  - Serum levels of nitrates in focal cerebral ischemia.
AB  - To ascertain the possible role of nitric oxide (NO) as risk factor for cerebral
      ischemia, we studied the serum levels of nitrate (oxidation product that provides
      an indirect estimation of NO), in 49 patients between the 3rd and 7th days after
      a cerebral ischemic event (TIAs, RIND and cerebral infarction) and in 65 matched
      controls. The serum levels of nitrate did not differ significantly between
      cerebral ischemic patient and control groups (42.6 +/- 334 and 44.8 +/- 2.67 +/-
      MUmol/l, respectively). They were not influenced by age, blood pressure, or
      smoking and alcohol-drinking habits. These results suggest that serum levels of
      nitrate are apparently unrelated to the risk for cerebral ischemia. 

PMID- 24283645
TI  - A double-blind, placebo-controlled, enriched population study of tacrine in
      patients with Alzheimer's disease.
AB  - The efficacy of tacrine in the treatment of patients with probable Alzheimer's
      disease (AD) was evaluated in a double-blind, placebo-controlled, enriched
      population multicenter study in France. A total of 280 patients entered the dose
      titration phase of the study. The assessment of potential benefit of tacrine
      ("best dose") was based on demonstrating improvement on the Alzheimer's Disease
      Assessment Scale (ADAS) total score versus a blinded placebo. One hundred and
      thirty of 242 (54%) patients achieved a "best dose" and were eligible for the
      double-blind, parallel group (pivotal) phase. Primary efficacy measures were ADAS
      Cognitive and Clinical Global Impression of Change; secondary efficacy measures
      of cognition and activities of daily living were also included. Results indicated
      that tacrine-treated patients showed improved functioning based on the ADAS
      Cognitive in comparison to placebo-treated patients. Transaminase elevations
      above the upper limit of normal occurred in 32% of patients, were more frequent
      in women than in men, demonstrated a delayed onset, and returned to normal limits
      for all patients following discontinuation of treatment The results from this
      study are supportive of the efficacy of tacrine in the treatment of AD as
      demonstrated in a study of similar design conducted in the US and studies using
      different designs. 

PMID- 24283646
TI  - Differential diagnosis of early stage Huntington's disease from dentatorubral
      pallidoluysian atrophy by DNA analysis.

PMID- 24283647
TI  - Acute sensory neuropathy: 2 year follow-up of sensory conduction.
AB  - Following flu-like illness a 75 year old man developed pure sensory neuropathy
      that reached a peak at 3 weeks. Cerebrospinal fluid protein was elevated with no
      increase in cell count The sensory deficits started to improve 4 months later,
      and were completely resolved 12 months later. Compound sensory nerve action
      potential, which had been absent initially, became detectable 8 months after the
      onset The revived sensory potentials progressively increased their size during
      the 2 year period. A variant of acute inflammatory demyelinating polyneuropathy
      may be part of a syndrome of acute sensory neuropathy. 

PMID- 24283648
TI  - Current issues in neurology.
AB  - Current Issues in Neurology was the title of a meeting for UK neurologists held
      at the Gloucester Hotel in London, on the 25/26th May. This is the fourth annual
      symposium organised by Glaxo Pharmaceuticals designed to meet some of the
      managerial training needs of the neurologist, whilst additionally looking at new
      and innovative research in associated fields of science. Dr David Bates
      (Consultant Neurologist, The Royal Victoria Infirmary, Newcastle-upon-Tyne)
      attended the symposium and has summarised the proceedings in the following paper.

PMID- 24283649
TI  - Opioids for the treatment of arthritis pain.
AB  - INTRODUCTION: Centrally acting opioids are well established in the treatment of
      acute, surgical and cancer pain. However, their use in chronic noncancer pain
      (CNCP) is controversial because of side effects such as tolerance, somnolence,
      respiratory depression, confusion, constipation and addiction. Chronic arthritis
      and other musculoskeletal diseases are among the leading causes of CNCP. AREAS
      COVERED: This manuscript will discuss the role of conventional opioids in chronic
      arthritis. In addition, future developments and strategies exploiting peripheral
      effects of opioids on pain and inflammation will be outlined. EXPERT OPINION:
      Aims in drug development include the design of peripherally restricted opioid
      agonists, selective targeting of endogenous opioids to sites of painful injury
      and the augmentation of peripheral ligand and receptor synthesis, for example, by
      gene therapy. Although a large number of peripherally acting opioid compounds
      have been developed, clinical Phase III studies have not been published so far.
      Another strategy is to augment the effects of endogenously released opioid
      peptides by the inhibition of their degrading enzymes. Technology-oriented
      research is needed to find novel ways of peripheral restriction of opioids. Such
      analgesics would be desirable for their lack of central side effects and of
      adverse effects typical of nonsteroidal anti-inflammatory drugs (gastrointestinal
      ulcers, bleeding, myocardial infarction and stroke).

PMID- 24283650
TI  - Differential responses to genotoxic agents between induced pluripotent stem cells
      and tumor cell lines.
AB  - Given potential values of induced pluripotent stem (iPS) cells in basic
      biomedical research and regenerative medicine, it is important to understand how
      these cells regulate their genome stability in response to environmental toxins
      and carcinogens. The present study characterized the effect of Cr(VI), a well
      known genotoxic agent and environmental carcinogen, on major molecular components
      of DNA damage response pathways in human iPS cells. We compared the effect of
      Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma
      origin) and BEAS-2B (lung epithelial origin). We also studied the effect of
      hydrogen peroxide and doxorubicin on modulating DNA damage responses in these
      cell types. We demonstrated that ATM and p53 phosphorylation is differentially
      regulated in human iPS cells compared with Tera-1 and BEAS-2B cells after
      exposure to various genotoxic agents. Moreover, we observed that inhibition of
      CK2, but not p38, promotes phosphorylation of p53S392 in iPS cells. Combined, our
      data reveal some unique features of DNA damage responses in human iPS cells. 

PMID- 24283651
TI  - Increased risk of preoperative venous thromboembolism in patients with renal cell
      carcinoma and tumor thrombus.
AB  - BACKGROUND: The clinical impact of a tumor thrombus in renal cell carcinoma (RCC)
      patients awaiting radical nephrectomy and thrombectomy is unknown. OBJECTIVE: To
      determine the incidence of venous thromboembolism (VTE) in RCC patients with
      tumor thrombus prior to nephrectomy. PATIENTS AND METHODS: We conducted a
      retrospective cohort study including all late-stage (stage 3-4 excluding T1-2
      N0M0) RCC patients who underwent radical nephrectomy at our institution between 1
      January 2005 and 1 July 2012. Tumor thrombus was defined as the presence of an
      intraluminal filling defect in the renal vein, hepatic vein, portal vein, or
      inferior vena cava, directly extending from a renal mass detected on computed
      tomography. RESULTS: A total of 176 patients were included in the study. Fifty
      three (30.1%) patients had tumor thrombus diagnosed on imaging Three patients
      with tumor thrombus (5.7%; 95% confidence interval [CI] 1.4-16.8) developed a VTE
      while awaiting radical nephrectomy, whereas none (0%; 95% CI 0-2.9) of the
      patients without a tumor thrombus had an event (P = 0.026). All three events were
      deep vein thrombosis. Times from tumor thrombus diagnosis to VTE were 5, 15 and
      21 days. CONCLUSIONS: Tumor thrombus on imaging is a frequent finding among RCC
      patients awaiting nephrectomy. The presence of tumor thrombus in these patients
      increases the incidence of preoperative VTE.

PMID- 24283652
TI  - Development of an air-stable nickel precatalyst for the amination of aryl
      chlorides, sulfamates, mesylates, and triflates.
AB  - A new air-stable nickel precatalyst for C-N cross-coupling is reported. The
      developed catalyst system displays a greatly improved substrate scope for C-N
      bond formation to include both a wide range of aryl and heteroaryl electrophiles
      and aryl, heteroaryl, and alkylamines. The catalyst system is also compatible
      with a weak base, allowing the amination of substrates containing base-sensitive
      functional groups. 

PMID- 24283654
TI  - Ceramides in the skin lipid membranes: length matters.
AB  - Ceramides are essential constituents of the skin barrier that allow humans to
      live on dry land. Reduced levels of ceramides have been associated with skin
      diseases, e.g., atopic dermatitis. However, the structural requirements and
      mechanisms of action of ceramides are not fully understood. Here, we report the
      effects of ceramide acyl chain length on the permeabilities and biophysics of
      lipid membranes composed of ceramides (or free sphingosine), fatty acids,
      cholesterol, and cholesterol sulfate. Short-chain ceramides increased the
      permeability of the lipid membranes compared to a long-chain ceramide with maxima
      at 4-6 carbons in the acyl. By a combination of differential scanning
      calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, Langmuir
      monolayers, and atomic force microscopy, we found that the reason for this effect
      in short ceramides was a lower proportion of tight orthorhombic packing and phase
      separation of continuous short ceramide-enriched domains with shorter lamellar
      periodicity compared to native long ceramides. Thus, long acyl chains in
      ceramides are essential for the formation of tightly packed impermeable lipid
      lamellae. Moreover, the model skin lipid membranes are a valuable tool to study
      the relationships between the lipid structure and composition, lipid
      organization, and the membrane permeability. 

PMID- 24283655
TI  - In vitro analysis of human periodontal microvascular endothelial cells.
AB  - BACKGROUND: Endothelial cells (ECs) participate in key aspects of vascular
      biology, such as maintenance of capillary permeability, initiation of
      coagulation, and regulation of inflammation. According to previous reports, ECs
      have revealed highly specific characteristics depending on the organs and
      tissues. However, some reports have described the characteristics of the
      capillaries formed by human periodontal ECs. Therefore, the aim of the present
      study is to examine the functional characteristics of the periodontal
      microvascular ECs in vitro. METHODS: Human periodontal ligament-endothelial cells
      (HPDL-ECs) and human gingiva-endothelial cells (HG-ECs) were isolated by
      immunoprecipitation with magnetic beads conjugated to a monoclonal anti-CD31
      antibody. The isolated HPDL-ECs and HG-ECs were characterized to definitively
      demonstrate that these cell cultures represented pure ECs. Human umbilical-vein
      ECs and human dermal microvascular ECs were used for comparison. These cells were
      compared according to the proliferation potential, the formation of capillary
      like tubes, the transendothelial electric resistance (TEER), and the expression
      of tight junction proteins. RESULTS: HPDL-ECs and HG-ECs with characteristic
      cobblestone monolayer morphology were obtained, as determined by light microscopy
      at confluence. Furthermore, the HPDL-ECs and HG-ECs expressed the EC markers
      platelet endothelial cell adhesion molecule-1 (also known as CD31), von
      Willebrand factor, and Ulex europaeus agglutinin 1, and the cells stained
      strongly positive for CD31 and CD309. In addition, the HPDL-ECs and HG-ECs were
      observed to form capillary-like tubes, and they demonstrated uptake of acetylated
      low-density lipoprotein. Functional analyses of the HPDL-ECs and HG-ECs showed
      that, compared to the control cells, tube formation persisted for only a brief
      period of time, and TEER was substantially reduced at confluence. Furthermore,
      the cells exhibited delocalization of zonula occludens-1 and occludin at cell
      cell contact sites. CONCLUSIONS: The present results provide new evidence that
      HPDL-ECs and HG-ECs have characteristics of fenestrated capillaries. Therefore,
      capillaries in human periodontal tissues have functional characteristics of
      fenestrated capillaries, which might be related to the onset and the progression
      of systemic diseases and inflammation.

PMID- 24283656
TI  - Cimetidine reduces alveolar bone loss in induced periodontitis in rat molars.
AB  - BACKGROUND: There is evidence that histamine released during inflammation plays a
      role in bone metabolism via the H2 receptor, stimulating bone resorption. The
      purpose of this study is to evaluate whether cimetidine, a histamine H2-receptor
      antagonist, interferes with the initiation and progression of induced periodontal
      disease in rat molars. METHODS: Forty male rats received 100 mg/kg body weight of
      cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]).
      Periodontal disease was induced in the maxillary left first molars (PDSG and
      PDCimG); maxillary right molars were used as non-ligature controls. After 7, 15,
      30, and 50 days, maxillary fragments were embedded in paraffin. The sections were
      stained with Masson trichrome and hematoxylin and eosin and subjected to the
      tartrate-resistant acid phosphatase (TRAP) method. The distances between the
      cemento-enamel junction (CEJ) and alveolar process (AP) crest, as well as between
      the CEJ and junctional epithelium (JE) level, were measured; the number of
      inflammatory cells was computed. Receptor activator of nuclear factor kappa B
      ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out,
      and the RANKL/OPG ratio was calculated. RESULTS: In PDSG and PDCimG, a
      significant increase (P <=0.05) was observed in CEJ-AP and CEJ-JE distances.
      However, the increases in both distances were significantly less in PDCimG
      compared with PDSG at 15, 30, and 50 days. Numerous TRAP-positive osteoclasts
      were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory
      cells and the RANKL/OPG ratio were significantly lower (P <=0.05) than in PDSG.
      CONCLUSIONS: Cimetidine exerts a beneficial effect on periodontal disease in
      rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing
      alveolar bone resorption.

PMID- 24283657
TI  - Outcome of enamel matrix derivative treatment in the presence of chronic stress:
      histometric study in rats.
AB  - BACKGROUND: Psychologic stress and clinical hypercortisolism have been related to
      direct effects on bone metabolism. However, there is a lack of information
      regarding the outcomes of regenerative approaches under the influence of chronic
      stress (CS). Enamel matrix derivative (EMD) has been used in periodontal
      regenerative procedures, resulting in improvement of clinical parameters. Thus,
      the aim of this histomorphometric study is to evaluate the healing of periodontal
      defects after treatment with EMD under the influence of CS in the rat model.
      METHODS: Twenty Wistar rats were randomly assigned to two groups; G1: CS
      (restraint stress for 12 hours/day) (n = 10), and G2: not exposed to CS (n = 10).
      Fifteen days after initiation of CS, fenestration defects were created at the
      buccal aspect of the first mandibular molar of all animals from both groups.
      After the surgeries, the defects of each animal were randomly assigned to two
      subgroups: non-treated control and treated with EMD. The animals were euthanized
      21 days later. RESULTS: G1 showed less bone density (BD) compared to G2. EMD
      provided an increased defect fill (DF) in G1 and higher BD and new cementum
      formation (NCF) in both groups. The number of tartrate-resistant acid phosphatase
      positive osteoclasts was significantly higher in G1 when compared to G2 and in
      EMD-treated sites of both groups. CONCLUSIONS: CS may produce a significant
      detrimental effect on BD. EMD may provide greater DF compared to non-treated
      control in the presence of CS and increased BD and NCF in the presence or absence
      of CS.

PMID- 24283658
TI  - Matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP-1 (TIMP-1) gene
      polymorphisms in generalized aggressive periodontitis: gingival crevicular fluid
      MMP-8 and TIMP-1 levels and outcome of periodontal therapy.
AB  - BACKGROUND: The aim of the present study is to investigate matrix
      metalloproteinase (MMP)-8 and tissue inhibitor of MMP-1 (TIMP-1) gene
      polymorphisms in generalized aggressive periodontitis (GAgP) and to assess the
      effects of MMP-8 and TIMP-1 genotypes on the outcomes of non-surgical periodontal
      therapy. METHODS: Genomic DNA was obtained from peripheral blood of 100 patients
      with GAgP and 167 periodontally healthy controls. MMP-8 +17 C/G, -799 C/T, -381
      A/G and TIMP-1 372 T/C, *429 T/G polymorphisms were determined by polymerase
      chain reaction-restriction fragment length polymorphism. Patients with GAgP
      received non-surgical periodontal therapy and were followed for 6 months.
      Clinical periodontal parameters and gingival crevicular fluid (GCF) samples were
      collected at baseline and at follow-up visits. GCF biomarkers were analyzed by
      immunofluorescence assay and enzyme-linked immunosorbent assay. RESULTS:
      Distribution of the MMP-8 -799 C/T genotypes was significantly different between
      the GAgP and control groups (P <0.005). TIMP-1 372 T/C and *429 T/G genotypes in
      males were also significantly different between study groups (P <0.004). GCF MMP
      8 levels decreased until 3 months after non-surgical therapy compared with
      baseline in T and G alleles, as well as G and C allele carriers (P <0.0125),
      whereas no significant decreased was observed in non-carriers (P >0.0125).
      CONCLUSION: On the basis of the present findings, it can be suggested that MMP-8 
      799 C/T and TIMP-1 372 T/C, *429 T/G gene polymorphisms in males may be
      associated with the susceptibility to GAgP in the Turkish population.

PMID- 24283659
TI  - Exploring revictimization risk in a community sample of sexual assault survivors.
AB  - Previous research points to links between risk detection (the ability to detect
      danger cues in various situations) and sexual revictimization in college women.
      Given important differences between college and community samples that may be
      relevant to revictimization risk (e.g., the complexity of trauma histories), the
      current study explored the link between risk detection and revictimization in a
      community sample of women. Community-recruited women (N = 94) reported on their
      trauma histories in a semistructured interview. In a laboratory session,
      participants listened to a dating scenario involving a woman and a man that
      culminated in sexual assault. Participants were instructed to press a button
      "when the man had gone too far." Unlike in college samples, revictimized
      community women (n = 47) did not differ in terms of risk detection response times
      from women with histories of no victimization (n = 10) or single victimization (n
      = 15). Data from this study point to the importance of examining revictimization
      in heterogeneous community samples where risk mechanisms may differ from college
      samples. 

PMID- 24283660
TI  - Tacrolimus-related seizure after pediatric liver transplantation--a single-center
      experience.
AB  - To identify the risk factors for new-onset seizures after pediatric LT and to
      assess their clinical implications and long-term prognosis. The clinical and
      laboratory data of 27 consecutive children who underwent LT from January 2007 to
      December 2010 in our center were analyzed retrospectively. Patients were divided
      into seizures group and a non-seizures group. Pre-operative, intra-operative, and
      post-operative data were collected. Seizures occurred in four children, an
      incidence of 14.8%. All exhibited generalized tonic-clonic seizures within the
      first two wk after LT. Univariate analysis showed that the risk factors
      associated with seizures after pediatric LT included gender, pediatric end-stage
      liver disease score before surgery, Child-Pugh score before surgery, serum total
      bilirubin after surgery, and trough TAC level. Multivariate analysis showed that
      trough TAC level was the only independent risk factor associated with the
      seizures. All children who experienced seizures survived with good graft function
      and remained seizure-free without anti-epileptic drugs over a mean follow-up
      period of 33.7 +/- 14.6 months. High trough TAC level was the predominant factor
      that contributed to seizures in the early post-operative period after pediatric
      LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil
      may be contributory risk factors for TAC-related seizures.

PMID- 24283661
TI  - Parasagittal cranial fasciitis following infratemporal fossa rhabdomyosarcoma.
AB  - Cranial fasciitis is a rare lesion of young children characterized by
      proliferation of fibroblastic spindle cells. Most are scalp masses and are only
      rarely intracranial, where an association with radiation therapy is exceptional.
      We report a 32-month-old toddler with a facial rhabdomyosarcoma, diagnosed at 3
      months of age, and treated with surgery, chemotherapy and brachytherapy. Brain
      MRI at 28 months revealed a large, left parasagittal, dural-based, T2
      hyperintense and T1 hypointense enhancing mass with superior sagittal sinus
      compression and bony hyperostosis. The mass was completely resected during an
      open craniotomy. Histologically, the lesion was comprised of loosely and
      haphazardly arranged bland spindle cells embedded in a myxoid background. Thick
      hyalinized collagen bundles were especially prominent. The spindle cells reacted
      for vimentin but not SMA, myogenin, MyoD1 or EMA. A diagnosis of cranial
      fasciitis was rendered. The role of radiation therapy in the pathogenesis of
      intracranial cranial fasciitis is discussed. 

PMID- 24283663
TI  - Boron nitride ultrathin fibrous nanonets: one-step synthesis and applications for
      ultrafast adsorption for water treatment and selective filtration of
      nanoparticles.
AB  - Novel boron nitride (BN) ultrathin fibrous networks are firstly synthesized via
      an one-step solvothermal process. The average diameter of BN nanofibers is only
      ~8 nm. This nanonets exhibit excellent performance for water treatment. The
      maximum adsorption capacity for methyl blue is 327.8 mg g(-1). Especially, they
      present the property of ultrafast adsorption for dye removal. Only ~1 min is
      enough to almost achieve the adsorption equilibrium. In addition, the BN fibrous
      nanonets could be applied for the size-selective separation of nanoparticles via
      a filtration process.

PMID- 24283662
TI  - Advanced sleep phase in adolescents born preterm.
AB  - The objective of this article is to evaluate whether sleep patterns and quality
      differed between adolescents born preterm and term, and to further explore
      whether differences in sleep patterns were explained by differences in mediating
      factors such as mood, behavior, or socioeconomic status. Five hundred and one 16-
      to 19-year-old children in the longitudinal Cleveland Children's Sleep and Health
      Study cohort underwent overnight polysomnography (PSG), wore wrist actigraphs,
      and completed sleep logs for 1 week. The modified Epworth Sleepiness Scale, the
      Adolescent Sleep Hygiene Scale, and the Adolescent Sleep-Wake Scale were used to
      further assess sleep. Adolescents born preterm demonstrated significantly (p <
      .05) earlier bed and wake times and sleep midpoints (approximately 22 min after
      adjusting for demographic and psychosocial factors) by actigraphy. They also had
      significantly fewer arousals (by PSG), and reported being more rested and alert
      in the morning, as well as less sleepiness and fatigue. These findings support a
      growing body of evidence that perinatal factors may influence sleep phenotypes
      later in life. These factors may reflect developmental influences, as well as the
      influence of parenting styles on children's sleep. 

PMID- 24283664
TI  - Recipient of the 2013 Molecular Ecology Prize: Laurent Excoffier.

PMID- 24283666
TI  - Vasopressin induces rectosigmoidal mucosal ischemia during cardiopulmonary
      bypass.
AB  - BACKGROUND: Lower gastrointestinal complications are rare after cardiac surgery
      with cardiopulmonary bypass (CPB). However, if they occur, they are associated
      with a high mortality. Endothelin (ET) expression and microcirculatory
      dysfunction have been shown to be involved in a variety of diseases of the lower
      gastrointestinal tract. The aim of this study was to analyze whether CPB with or
      without additional vasopressin administration affects the rectosigmoidal mucosal
      microcirculation and whether this involves the ET system. METHODS: Pigs were
      randomized in three groups (n = 6 each): I Sham, II CPB: 1 hour CPB, III CPB +
      vasopressin: 1 hour CPB and vasopressin (0.006 U/min kg) administration
      maintaining baseline arterial pressure. All animals were reperfused for 90
      minutes. During the experiment hemodynamics and rectosigmoidal mucosal
      microcirculation were measured continuously. The rectosigmoidal mucosal
      expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA ) and B (ETB )
      were determined using PCR and Western blot analysis. RESULTS: CPB did not change
      rectosigmoidal microvascular blood flow compared to baseline (68.1 +/- 4.0 vs.
      75.5 +/- 6.6 AU; p = 0.4), but increased ET-1 (gene, 7.8 +/- 1.5 vs. 2.3 +/- 0.6
      RQ; p = 0.002 and protein, 12.0 +/- 0.5 vs. 6.9 +/- 0.3 OD mm(2) ; p < 0.001),
      ETA (gene, 2.3 +/- 0.6 vs. 0.6 +/- 0.1 RQ; p < 0.001 and protein, 11.0 +/- 0.3
      vs. 6.2 +/- 1.1 OD mm(2) ; p = 0.006) and ETB (gene, 6.7 +/- 1.2 vs. 1.9 +/- 0.3
      RQ; p < 0.001 and protein, 25.6 +/- 1.4 vs. 14.9 +/- 1.5 OD mm(2) ; p = 0.002)
      expression compared to Sham. Vasopressin during CPB reduced the rectosigmoidal
      blood flow compared to baseline (26.5 +/- 4.9 vs. 75.5 +/- 6.6 AU, p < 0.001),
      and blunted the CPB-induced increase of ET-1 (gene, 1.2 +/- 0.4 RQ, p = 0.1 and
      protein, 8.1 +/- 1.6 OD mm(2) , p = 0.5 vs. Sham), ETA (gene, 0.6 +/- 0.1 RQ, p =
      1.0 and protein, 7.0 +/- 0.6 OD mm(2) , p = 0.6 vs. Sham) and ETB (gene, 1.3 +/-
      0.3 RQ, p = 0.1 and protein, 19.4 +/- 2.1 OD mm(2) , p = 0.1 vs. Sham).
      CONCLUSION: CPB does not significantly affect rectosigmoidal mucosal
      microcirculation; however, it upregulates ET-1, ETA , and ETB . Vasopressin
      blunts the CPB-induced elevation of ET-1, ETA , and ETB and induces
      rectosigmoidal mucosal ischemia during CPB.

PMID- 24283665
TI  - Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately
      predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate.
AB  - BACKGROUND AND PURPOSE: In vitro inhibitory potency (Ki )-based predictions of P
      glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) are hampered by the
      substantial variability in inhibitory potency. In this study, in vivo-based
      [I]/Ki values were used to predict the DDI risks of a P-gp substrate dabigatran
      etexilate (DABE) using physiologically based pharmacokinetic (PBPK) modelling.
      EXPERIMENTAL APPROACH: A baseline PBPK model was established with digoxin, a
      known P-gp substrate. The Km (P-gp transport) of digoxin in the baseline PBPK
      model was adjusted to Km (i) to fit the change of digoxin pharmacokinetics in the
      presence of a P-gp inhibitor. Then 'in vivo' [I]/Ki of this P-gp inhibitor was
      calculated using Km (i) /Km . Baseline PBPK model was developed for DABE, and the
      'in vivo' [I]/Ki was incorporated into this model to simulate the static effect
      of P-gp inhibitor on DABE pharmacokinetics. This approach was verified by
      comparing the observed and the simulated DABE pharmacokinetics in the presence of
      five different P-gp inhibitors. KEY RESULTS: This approach accurately predicted
      the effects of five P-gp inhibitors on DABE pharmacokinetics (98-133% and 89-104%
      for the ratios of AUC and Cmax respectively). The effects of 16 other P-gp
      inhibitors on the pharmacokinetics of DABE were also confidently simulated.
      CONCLUSIONS AND IMPLICATIONS: 'In vivo' [I]/Ki and PBPK modelling, used in
      combination, can accurately predict P-gp-mediated DDIs. The described framework
      provides a mechanistic basis for the proper design of clinical DDI studies, as
      well as avoiding unnecessary clinical DDI studies.

PMID- 24283667
TI  - Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 regulates
      epinephrine-induced exocytosis of Weibel-Palade bodies.
AB  - BACKGROUND: Weibel-Palade bodies (WPBs) function as storage vesicles for von
      Willebrand factor (VWF) and a number of other bioactive compounds, including
      angiopoietin-2 and insulin-like growth factor-binding protein 7. WPBs release
      their content following stimulation with agonists that increase the level of
      intracellular Ca2+, such as thrombin, or agonists that increase intracellular
      levels of cAMP, such as epinephrine. OBJECTIVE: Previously, we have shown that
      the exchange protein activated by cAMP, exchange protein activated by cAMP, and
      the small GTPase Rap1 are involved in cAMP-mediated release of WPBs. In this
      study, we explored potential downstream effectors of Rap1 in cAMP-mediated WPB
      release. METHODS: Studies were performed in primary human umbilical vein
      endothelial cells. Activation of the small GTP-binding protein Rac1 was monitored
      by its ability to bind to the CRIB domain of the serine/threonine kinase P21
      activated kinase (PAK)1. Downstream effectors of Rap1 were identified with a
      proteomic screen using a glutathione-S-transferase fusion of the Ras-binding
      domain of RalGDS. Functional involvement of candidate proteins in WPB release was
      determined by RNA interference (RNAi)-mediated knockdown of gene expression.
      RESULTS: Depletion of Rac1 by RNAi prevented epinephrine-induced VWF secretion.
      Also, the Rac1 inhibitor EHT1864 reduced epinephrine-induced WPB release. We
      identified the phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange
      factor 1 (PREX1) and the regulatory beta-subunit of phosphatidylinositol 3-kinase
      (PI3K) as downstream targets of Rap1. The PI3K inhibitor LY294002 reduced
      epinephrine-induced release of VWF. RNAi-mediated downregulation of PREX1
      abolished epinephrine-induced but not thrombin-induced release of WPBs.
      CONCLUSION: Our findings show that PREX1 regulates epinephrine-induced release of
      WPBs.

PMID- 24283669
TI  - Observational attachment theory-based parenting measures predict children's
      attachment narratives independently from social learning theory-based measures.
AB  - Conceptually and methodologically distinct models exist for assessing quality of
      parent-child relationships, but few studies contrast competing models or assess
      their overlap in predicting developmental outcomes. Using observational
      methodology, the current study examined the distinctiveness of attachment theory
      based and social learning theory-based measures of parenting in predicting two
      key measures of child adjustment: security of attachment narratives and social
      acceptance in peer nominations. A total of 113 5-6-year-old children from
      ethnically diverse families participated. Parent-child relationships were rated
      using standard paradigms. Measures derived from attachment theory included
      sensitive responding and mutuality; measures derived from social learning theory
      included positive attending, directives, and criticism. Child outcomes were
      independently-rated attachment narrative representations and peer nominations.
      Results indicated that Attachment theory-based and Social Learning theory-based
      measures were modestly correlated; nonetheless, parent-child mutuality predicted
      secure child attachment narratives independently of social learning theory-based
      measures; in contrast, criticism predicted peer-nominated fighting independently
      of attachment theory-based measures. In young children, there is some evidence
      that attachment theory-based measures may be particularly predictive of
      attachment narratives; however, no single model of measuring parent-child
      relationships is likely to best predict multiple developmental outcomes.
      Assessment in research and applied settings may benefit from integration of
      different theoretical and methodological paradigms. 

PMID- 24283668
TI  - Quantitative proteomic analysis in HCV-induced HCC reveals sets of proteins with
      potential significance for racial disparity.
AB  - BACKGROUND: The incidence and mortality of hepatitis C virus (HCV)-induced
      hepatocellular carcinoma (HCC) is higher in African Americans (AA) than other
      racial/ethnic groups in the U.S., but the reasons for this disparity are unknown.
      There is an urgent need for the discovery of novel molecular signatures for HCV
      disease progression to understand the underlying biological basis for this cancer
      rate disparity to improve the clinical outcome. METHODS: We performed
      differential proteomics with isobaric labeling tags for relative and absolute
      quantitation (iTRAQ) and MS/MS analysis to identify proteins differentially
      expressed in cirrhotic (CIR) and HCC as compared to normal tissues of Caucasian
      American (CA) patients. The raw data were analyzed using the ProteinPilot v3.0.
      Searches were performed against all known sequences populating the Swiss-Prot,
      Refseq, and TrEMBL databases. Quality control analyses were accomplished using
      pairwise correlation plots, boxplots, principal component analysis, and
      unsupervised hierarchical clustering. Supervised analysis was carried out to
      identify differentially expressed proteins. Candidates were validated in
      independent cohorts of CA and AA tissues by qRT-PCR or Western blotting. RESULTS:
      A total of 238 unique proteins were identified. Of those, around 15% were
      differentially expressed between normal, CIR & HCC groups. Target validation
      demonstrates racially distinct alteration in the expression of certain proteins.
      For example, the mRNA expression levels of transferrin (TF) were 2 and18-fold
      higher in CIR and HCC in AA as compared to CA. Similarly; the expression of
      Apolipoprotein A1 (APOA1) was 7-fold higher in HCC of AA. This increase was
      mirrored in the protein expression levels. Interestingly, the level of hepatocyte
      nuclear factor4a (HNF4a) protein was down regulated in AA, whereas repression of
      transcription is seen more in CA compared to AA. These data suggest that racial
      disparities in HCC could be a consequence of differential dysregulation of HNF4a
      transcriptional activity. CONCLUSION: This study identifies novel molecular
      signatures in HCV-induced HCC using iTRAQ-based tissue proteomics. The proteins
      identified will further enhance a molecular explanation to the biochemical
      mechanism(s) that may play a role in HCC racial disparities.

PMID- 24283670
TI  - High seroprevalence of human herpesvirus 8 infection in patients with systemic
      lupus erythematosus.
AB  - AIM: Systemic lupus erythematosus (SLE) is an autoimmune disease that is
      associated with genetic and environmental factors and microbial infection. With
      respect to microbial infection, the Epstein-Barr virus (EBV) has been a widely
      discussed issue in recent decades. Human herpesvirus 8 (HHV-8) belongs to the
      same gamma-herpesvirus subfamily as EBV and is closely related to it. Until now,
      only one paper has reported the prevalence of HHV-8 infection in SLE patients.
      The goal of this study was to detect the prevalence of HHV-8 infection in SLE
      patients to elucidate the relationship between HHV-8 and SLE. METHODS: We
      assessed the seroprevalence of HHV-8 in SLE patients by immunofluorescence assay.
      In addition, we quantified the HHV-8 DNA in peripheral blood mononuclear cells
      (PBMCs) from SLE patients by real-time polymerase chain reaction (PCR). RESULTS:
      The prevalence of HHV-8 antibodies in SLE and normal controls was 57.8% (26/45)
      and 19.2% (5/26), respectively. These data were highly significant (P = 0.001).
      No HHV-8 DNA was detected by real-time PCR in SLE patients' PBMCs. In addition,
      we analyzed the prevalence of HHV-8 infection in patients with rheumatoid
      arthritis and ankylosing spondylitis. There was no significant difference between
      the patients and normal controls. CONCLUSION: A high seroprevalence of HHV-8
      infection was found in patients with SLE. The negative DNA load and high
      seropositive rate indicate that most patients might have latent infection.

PMID- 24283671
TI  - Developments in contraception.
AB  - INTRODUCTION: Although the contraceptive options for women have expanded
      considerably in the last decade, these methods are often not being offered to
      women as choices because clinicians are not well informed, limiting the ability
      of women to control their fertility. AREAS COVERED: Areas covered include the use
      of oestradiol instead of ethinyl oestradiol and improved progestogens utilised in
      hormonal contraceptives, and new delivery systems have enabled the development of
      long-acting methods, which require less action on the part of the user, and
      thereby, reduce failure rates. Effective emergency contraceptive methods have
      become more readily available over the counter. However, male contraception,
      despite much research, still remains elusive. EXPERT OPINION: This manuscript
      will provide an assessment of recent advances and controversies in contraception
      and make suggestions about improved availability.

PMID- 24283672
TI  - Interconnectivity of sympathetic and sleep networks is mediated through reduction
      of gamma aminobutyric acidergic inhibition in the paraventricular nucleus.
AB  - Chronic short sleep duration has been linked to sympathoexcitation and increased
      risk of cardiovascular disease. The central nervous system plays an important
      role in the regulation of sympathetic activity. Thus, the present study evaluates
      the pre-autonomic neurones in the paraventricular nucleus of the hypothalamus and
      rostral ventrolateral medulla after sleep restriction using various protein
      expression measurements and electrophysiological approaches. Wistar male rats
      were assigned randomly to two experimental groups: control or sleep restriction
      for 14 days. Sleep restriction was defined as 20 h of paradoxical sleep
      deprivation followed by a 4 h sleep permission period using the modified multiple
      platform method. Micropunches of the paraventricular nucleus of the hypothalamus
      and rostral ventrolateral medulla were dissected to evaluate the protein
      expression of angiotensin II receptor, type 1 (AT1), AT2, gamma aminobutyric
      acidA ) (N-methyl-d-aspartate receptor1) and neuronal nitric oxide synthase
      neuronal nitric oxide synthase isoform through immunoblotting. Sleep restriction
      induced a down-regulation of the gamma aminobutyric acidA receptor in the
      paraventricular nucleus of the hypothalamus. Microinjection of bicuculline, a
      gamma aminobutyric acid receptor blocker, into the paraventricular nucleus of the
      hypothalamus increased renal sympathetic activity renal sympathetic nerve
      activity, mean arterial pressure and heart rate in anaesthetized control rats.
      However, the amplitude and frequency of renal sympathetic nerve activity was
      higher in the sleep restriction group. These findings suggest that gamma
      aminobutyric acidergic inhibition within the paraventricular nucleus of the
      hypothalamus is involved in sympathoexcitation induced by sleep restriction. 

PMID- 24283673
TI  - Cost-effective application of thermal protection on LPG road transport tanks for
      risk reduction due to hot BLEVE incidents.
AB  - A simplified risk and cost-benefit analysis is presented for the application of
      thermal protection (TP) on propane and LPG highway tanker trucks operating in
      North America. A risk analysis is performed to determine the benefits of risk
      reduction by TP, relative to the costs of applying and maintaining TP on a tanker
      truck. The results show that TP is cost effective if the tanker truck spends
      enough time (or travels enough distance) in areas of moderate or high population
      density. The analysis is very sensitive to a number of inputs, including: (i)
      value of life, (ii) hot boiling liquid expanding vapor explosion frequency, (iii)
      public exposure to severe hazards, and (iv) life cost of TP. With this simplified
      analysis, it is possible to generate tanker truck exposure times to the public
      that justify the application of TP based on cost and benefit considerations. 

PMID- 24283675
TI  - Platinum group element pollution is a growing concern in countries with
      developing economy.

PMID- 24283674
TI  - Individual, provider, and system risk factors for breast and cervical cancer
      screening among underserved Black, Latina, and Arab women.
AB  - BACKGROUND: Socioeconomic and racial/ethnic disparities in breast and cervical
      cancer screening persist. An exploratory study was conducted to better understand
      co-occurring risk factors in underserved groups that could inform interventions
      to improve screening adherence. The objective of this study was to examine
      associations between breast and cervical cancer screening adherence and co
      occurring risk factors in three racial/ethnic groups of underserved women.
      METHODS: Black, Latina, and Arab women (N=514), ages 21 to 70 years, were
      enrolled into the Kin Keeper(SM) randomized controlled trial in communities
      around Detroit, Michigan. We used participant baseline assessments (e.g.,
      demographic characteristics, health literacy) to explore screening risks using an
      additive approach and multivariate logistic analyses. RESULTS: For black women,
      having more health literacy risks were associated with reduced odds of a clinical
      breast exam (CBE), mammogram, and Papanicolaou (Pap) test; more competing
      priorities were associated with reduced odds of a Pap test; lack of doctor
      mammogram recommendation was significantly associated with decreased odds of CBE.
      For Latina women, lack of doctor recommendations were significantly associated
      with decreased odds of CBE, mammogram, and Pap test. For Arab women, lack of
      doctor recommendations were significantly associated with decreased odds of CBE,
      mammogram, and Pap test; more competing priorities were significantly associated
      with reduced odds of CBE and Pap test. All results were significant at p<0.05.
      CONCLUSIONS: Characteristics associated with breast and cervical screening
      adherence differs among Black, Latina, and Arab underserved women. Interventions
      to improve screening should be tailored for racial/ethnic groups with particular
      attention to competing survival priorities, health literacy risks factors, and
      provider recommendations.

PMID- 24283676
TI  - Inexpensive and efficient Ullmann methodology to prepare donor-substituted
      porphyrins.
AB  - The preparation of porphyrins functionalized with one or two carbazoles (or
      phenoxazines) is described. The electron donors were introduced into one or two
      porphyrin meso positions by using the inexpensive Ullmann coupling procedure.
      Very good yields were obtained, and for two new compounds, the X-ray structures
      were solved. Preliminary electrochemical data coupled with electronic
      spectroscopy are also reported. 

PMID- 24283678
TI  - Progressive supranuclear palsy: clinical and pathological diagnosis.
AB  - Progressive supranuclear palsy (PSP) is an heterogeneous disorder, both
      clinically and pathologically and, in consequence, it is often difficult to
      diagnose. In this review we shall discuss those clinical settings in which it is
      difficult to make the diagnosis of PSP and review the pathology of the disorder.
      Clinical and pathological diagnostic criteria currently in use will also be
      discussed. 

PMID- 24283677
TI  - Currently recommended BK virus (BKV) plasma viral load cutoff of >=4 log10/mL
      underestimates the diagnosis of BKV-associated nephropathy: a single transplant
      center experience.
AB  - BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) is a major cause of
      renal dysfunction and graft loss in renal transplant recipients. Monitoring
      plasma BK viral load (BKVL) is the recommended screening tool to predict BKVAN.
      American Society of Transplantation (AST) guidelines define a BKVL of >=4
      log10/mL (10,000 copies) as presumptive BKVAN and recommend reduction in
      immunosuppression. We evaluated the clinical sensitivity of the quantitative BKV
      DNA assay in predicting risk for BKVAN using the AST-recommended BKVL cutoff.
      METHODS: In a retrospective, single-center study, all patients who underwent
      renal transplant at Henry Ford Hospital from January 2008 to August 2011 were
      analyzed (n = 490). Plasma BKVL Assay A (commercial large T antigen-based
      polymerase chain reaction [PCR]) was done in all patients. Renal biopsy was done
      if there was a rise in serum creatinine >=0.5 mg from baseline. BKVAN was
      confirmed by biopsy. As a subset to this study, from the same cohort, data for a
      set of 20 consecutive Assays A and B (in-house VP1-based PCR assay) from 15
      patients over a period of 3 months were collected. Differences in physicians'
      clinical decision-making (CDM) were analyzed between the 2 assays using chi
      square test. RESULTS: A total of 413 patients met the inclusion criteria, of
      which 222 patients had BK viremia. Among the 248 patients who had a renal biopsy
      done, 31 (12.5%) were found to have BKVAN. Eleven of the 31 (35%) patients had
      BKVL consistently <4 log10/mL, and thus were not diagnosed to have BKVAN using
      the AST-recommended BKVL cutoff of >=4 log10/mL. A total of 8 patients lost their
      graft owing to BKVAN, including 3 patients with BKVL <4 log10/mL. Using a cutoff
      point of plasma BKVL of >=4 log10/mL, the sensitivity, specificity, positive
      predictive value, and negative predicative value of the PCR Assay A for the
      diagnosis of biopsy-proven BKVAN were 64.5%, 98.4%, 87.0%, and 94.5%,
      respectively, and for the diagnosis of presumptive nephropathy were found to be
      76.6%, 99.4%, 95.8%, and 96.4%, respectively. In the second part of the study,
      presumptive nephropathy was detected in 8 samples using Assay A and 14 samples
      using Assay B. Six samples in Assay A would have led to no changes in the CDM in
      terms of reduction in immunosuppression. Kidney biopsy was carried out in 5
      patients, 4 of whom had BKVAN and had Assay B log count of >=5. If Assay A had
      been used in CDM, BKVAN would have been missed in 1 patient. CONCLUSION:
      Utilizing the current AST guideline cutoff of >=4 log10 /mL, the PCR Assay A
      underestimated the diagnosis of BKVAN. Urgent standardization of the various BKVL
      assays and establishment of universal cutoff points is imperative to avoid BKVAN
      related graft loss.

PMID- 24283679
TI  - Eye movements and fixation characteristics in perception of stationary scenes:
      normal subjects as compared to patients with visual neglect or hemianopia.
AB  - Saccade amplitudes, fixation times, and the spatial distribution of fixation
      points were comparatively studied in patients with visual hemineglect and/or
      homonymous hemianopia, as well as in normals (each group, n = 8). Two types of
      picture slides were presented (with and without search task) while eye movements
      were recorded with the infrared reflection technique. Self-developed software
      served to detect fixations, and to document their spatio-temporal parameters.
      Spectra of saccade amplitudes and fixation times were characteristic of each
      slide, while exhibiting notable similarities across subject groups. It is
      concluded that foveal information processing may not be much different in
      patients and in normals. Average saccade amplitudes and total scanpath lengths
      across all pictures were significantly smaller in the patients than in normals
      with both types of slides. In the neglect patients, saccades starting and
      terminating in the unaffected visual hemifield were larger, on an average, than
      those entirely located in the affected hemifield. The same was true for many of
      the hemianopic patients. Nevertheless, during free exploration, mean amplitudes
      of saccades restricted to the unaffected hemifield of the patients were
      apparently still smaller than those of normal controls within the corresponding
      hemifield. Average dwell time of fixations, total fixation time, as well as the
      total number of fixations did not vary significantly between groups. However, in
      the patient groups, average fixation times were shorter after large as compared
      to small saccades. This finding is discussed in the context of saccadic
      programming on the background of the sequential attention model of eye movement
      control. In subsamples of five hemianopic and six neglect patients, asymmetry in
      the distribution of fixation points was compared before and after a 4-week period
      of comprehensive rehabilitation that Included computerized scanning and
      attentional training. Only patients with pure hemianopia (who were less severely
      impaired from the beginning) improved according to this criterion, while neglect
      patients remained unchanged or deteriorated slightly. Total scanpath lengths,
      however, were not significantly different before and after therapy in any of the
      two groups of patients, indicating a persisting disturbance in scanning
      performance also in the hemianopic group. 

PMID- 24283680
TI  - A prospective study of "undiagnosed" isolated myelopathy: I. Case selection and
      clinical features.
AB  - We aimed to carry out a study of isolated, unexplained myelopathy which avoided
      as far as possible selection and referral bias. We used a prospective design with
      case ascertainment from both neurological and neurosurgical referrals. We wanted
      to establish the sensitivity, predictive value and possible redundancy of
      currently available tests as assessed by the proportion of such patients who
      finally developed clinically definite multiple sclerosis at follow up. Although
      MRI scanning of the spinal cord is now the investigation of choice for
      myelopathy, the case ascertainment for the present studies was completed, and
      follow-up commenced, before MRI became available to patients in our catchment
      region. We believe that this was an important factor in the ascertainment of a
      representative sample of undiagnosed myelopathies. Of 2104 patients having
      myelography in a 36-month period, 473 had signs of a myelopathy without lower
      motor neurone involvement Sixty-nine of these 473 patients (15%, 95% CI 11.8
      18.2) eventually satisfied the entry criteria for the prospective trial. Fourteen
      of the 69 patients (20%) presented with acute or subacute cord syndromes, while
      55 (80%) had chronic symptoms of more than 3 months duration. Approximately two
      thirds of the chronic cases were progressive and one-third relapsing and
      remitting. Overall there was a female predominance (3:2) and a significant excess
      of HLA-DR2 antigen compared with a healthy control population (p < 0.0001). In
      this series the patients with chronic unexplained myelopathy were younger and had
      shorter symptom durations (mean 46.5 months) and less disability (mean EDSS 3.0)
      than cases in other comparable published series. The neurological findings, sex
      distribution and HLA characteristics were similar to those found in patients with
      clinically definite MS. 

PMID- 24283681
TI  - A prospective study of "undiagnosed" isolated myelopathy: II. Value of magnetic
      resonance imaging, evoked potentials and CSF analysis.
AB  - We aimed to determine the sensitivity of available "diagnostic" tests in
      detecting subclinical abnormalities characteristic of multiple sclerosis (MS) in
      patients with unexplained isolated myelopathy, and any relationship between test
      results and level of disability. The trial investigations were carried out in 69
      prospectively selected patients with acute or chronic noncompressive
      myelopathies. Magnetic resonance scans were the most sensitive individual tests,
      revealing asymptomatic brain lesions in 51 patients (74%, C.I. 64-84). An
      abnormal IgG/albumin ratio (IgG/A) was present in 29 (42%, C.I. 30-54),
      oligoclonal bands (OCB) in 27 (39%, C.I. 17-39) and abnormal evoked potentials
      (EP) (visual and/or auditory brain stem) in 19 cases (28%, C.I. 17-39). OCB and
      abnormal EP were found significantly less often than in control patients with
      clinically definite MS (CDMS) and significantly more often than in patients with
      myelopathy due to other conditions. The number of anatomical brain areas with
      lesions on magnetic resonance imaging (MRI) was significantly associated with CSF
      abnormalities; abnormal EP were correlated with abnormal MRI and elevated CSF
      immunoglobulins. Clinical classifications, age, symptom duration, disability
      levels and genetic factors did not appear to influence the prevalence of abnormal
      MRI or CSF. For the exclusion of compressive and structural diseases of the
      spinal cord, myelography has been superceded by cervical and thoracic MRI. In
      addition, MRI of the brain is the investigation of choice in patients with
      myelopathies that remain unexplained after spinal MRI. However, whether used
      alone or in combination with other tests, the specificity and predictive value of
      brain MRI abnormalities for the risk of developing MS, as well as the associated
      "false positive" rates, remain to be defined by long-term follow-up of
      prospectively ascertained and representative cases. 

PMID- 24283682
TI  - Subcortical aphasia: a specific clinical picture?
AB  - 100 aphasic patients were examined with a scorable aphasia battery looking at the
      frequency of various aphasia types and the possible specificity of clinical
      pictures in deep-seated lesions. One month after onset, "atypical" aphasiological
      syndromes proved to be rare and to have the same frequency in patients with
      cortico-subcortical or capsulostriatal deep-seated lesions. In the latter
      condition, no specific clinical syndrome was brought out, although verbal
      comprehension disorders were usually less severe than in cortico-subcortical
      lesions. 

PMID- 24283683
TI  - Risk factors, diet and carotid atheromatosis in TIAs and minor ischemic strokes
      (MISs) in a Mediterranean country.
AB  - Eighty-two patients with transient ischemic attacks (TIAs) or minor ischemic
      strokes (MISs) were prospectively recruited from the emergency room of a general
      hospital within 1 month of the event with the aim of providing a group for
      comparison - regarding the pathogenetic profile - with similar series from
      Northern Europe and USA. Patients were asked a diet questionnaire, and serum
      lipid analysis, CT scan and carotid duplex were performed in each case. Relevant
      features were antecedents of hypertension in 61%, current smoking in 23.2% and
      ischemic heart disease in 13.5%; mean serum levels of cholesterol 6.2 mmol/l, LDL
      C, 4.27, HDL-C, 1.24, triglycerides 1.45; and duplex evidence of severe
      extracranial carotid atheromatosis (hemodinamically significant stenosis or
      occlusion) in 14.4%. Relevant diet data were daily intake of energy, 7.2 MJ, fat
      34% of energy and saturated fat 12.6%. Cases with severe carotid atheromatosis
      had significantly lower levels of HDL-C, higher levels of triglycerides and lower
      per cent of energy from monounsaturated fat (p < 0.05 Mann-Whitney test). When
      compared with series from Northern Europe and USA ours showed lower incidence of
      severe carotid atheromatosis and ischemic heart disease, lower levels of
      triglycerides and higher HDL-C, and lower mean diet energy and proportion of
      unsaturated fat We suggest that higher HDL-C and lower triglyceride serum levels
      could be protective against severe extracranial carotid atheromatosis and that a
      Mediterranean diet, with less saturated fat and more monounsaturated fat could
      account in part for this low incidence of severe carotid disease in our TIAs and
      MISs patients. 

PMID- 24283684
TI  - High level of anticardiolipin antibodies is an unusual finding in an unselected
      stroke population.
AB  - Anticardiolipin antibodies (ACA) were analysed in 502 consecutive patients
      admitted to our stroke unit Elevated ACA levels >=11 units) were found in 20 of
      396 patients (5%) with ischemic stroke and TIA, in none of 42 patients with
      cerebral haematomas and in five of 64 patients (8%) with other diagnoses than
      stroke. There were no statistically significant differences in occurrence of ACA
      in these groups. Markedly elevated ACA levels (> 20 units) were found in nine of
      the 396 patients (2%) with TIA/ischemic stroke. The frequency of ACA was higher
      in the age group 40-50 years (15%) than in the age group 50-90 years (3.6-6.0%).
      Re-examination in 18 of the 20 patients with ischemic stroke and elevated ACA
      levels after 26-395 days (mean 100 days) showed that in 10 patients ACA levels
      were lower (difference >= 6 units = 2 SD), compared to the initial value, whereas
      eight patients had unchanged ACA levels. The occurrence of previous deep venous
      thrombosis was significantly more common in patients with elevated ACA levels,
      otherwise there were no differences concerning earlier stroke, risk factor
      analysis or other laboratory parameters between patients with and without
      elevated ACA levels. In conclusion, we found elevated ACA levels in patients with
      ischemic stroke at a rather low prevalence as compared to most previous studies.
      The clinical relevance of ACA is uncertain, especially in patients with multiple
      risk factors. We recommend screening for ACA only in stroke patients < 50 years
      of age, or when the antiphospholipid syndrome is suspected. 

PMID- 24283685
TI  - Persistent increase of leukocyte aggregation in a patient with relapsing ischemic
      stroke and ulcerative colitis.
AB  - There is an increased incidence of central nervous system thromboembolic events
      in patients with inflammatory bowel disease. The possible pathogenetic link
      between the two diseases is not clear. Experimental and clinical observations
      suggest the possible role of leukocyte activation in the induction of ischemic
      and inflammatory events. In a patient with relapsing ischemic stroke and
      ulcerative colitis, serial determinations of leukocyte aggregation, by means of
      the modified leukergy test, were performed. A persistent increase of the
      percentage of aggregated leukocytes with values much higher than those of healthy
      subjects and patients with ischemic stroke was found during and between the
      episodes of ischemia and inflammation. The particular temporal pattern of
      clinical and hemorheological alterations suggests that the persistent activation
      of leukocytes may represent a risk factor for the development of both ischemic
      and inflammatory disease. 

PMID- 24283686
TI  - Entacapone in combination with standard or controlled-release levodopa/carbidopa:
      a clinical and pharmacokinetic study in patients with Parkinson's disease.
AB  - We investigated clinical response and pharmacokinetics of levodopa when
      entacapone, a catechol O-methyltransferase (COMT) inhibitor, was administered
      concomitantly with either a standard (Std) or a controlled-release (CR)
      levodopa/carbidopa preparation to 12 patients with Parkinson's disease. An open
      cross-over study consisted of the initial study day without entacapone followed
      by two 10-day treatment periods with a study day at the end of each period. The
      patients who received entacapone (200 mg t.i.d. or q.i.d.) concomitantly with Std
      levodopa/carbidopa (200/50 mg t.i.d. or q.i.d.) during the first period received
      subsequently entacapone with CR levodopa/carbidopa (200/50 mg t.i.d. or q.i.d.),
      and vice versa. On the study days, the patients took the medication at 8 a.m. and
      the second dose 6 h later. We evaluated the disability before drug administration
      and then 1-h intervals for 8 h. Repeated blood samples were taken for analysis of
      plasma levodopa, 3-O-methyldopa (3-OMD), dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA), carbidopa, and entacapone. Entacapone decreased
      significantly the clinical disability with both Std and CR levodopa, slightly
      more with Std levodopa. The clinical response started earlier with Std levodopa
      whereas the "on"-time increased by about 1 h, equally with both levodopa
      preparations. Std levodopa produced 23% higher area under the curve (AUC) of
      levodopa than the CR preparation, but entacapone increased the AUC approximately
      equally, 33% with Std and 36% with CR levodopa. Entacapone slightly decreased
      Cmax of levodopa in combination with Std levodopa, whereas it increased that with
      CR levodopa. The AUC of 3-OMD was about 20% smaller after Std than after CR
      levodopa. Entacapone decreased the AUC of 3-OMD by 38-40% with both levodopa
      preparations. Entacapone did not modify the AUC levels of carbidopa although its
      bioavailability was less from CR levodopa than from Std levodopa. In three
      patients levodopa dosage was reduced when on Std levodopa because of nausea.
      Otherwise, the treatments were well tolerated. The study shows that entacapone is
      an effective COMT inhibitor when combined with either Std levodopa or CR
      levodopa. 

PMID- 24283687
TI  - A family with mild clinical manifestations of spinocerebellar ataxia type 1
      (SCA1): correlation with smaller CAG repeats.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by
      expansion of a CAG trinucleotide repeat. We analyzed CAG repeat expansion in one
      Japanese SCA1 family with mild clinical manifestations. Clinically, this SCA1
      family showed less frequent nystagmus (p = 0.045, Fisher's exact-test) in
      comparison with duration-matched control patients with larger numbers of CAG
      repeats (48.4 +/- 4.2, p < 0.01). Some patients showed no other signs than
      cerebellar ataxia in the earlier stage. All six patients had expanded alleles for
      SCA1 with relatively small CAG repeats (41.5 +/- 1.0, mean +/- SD), which may be
      related to the mild clinical symptoms of the disease. The present results also
      suggest that slow saccades and amyotrophy are constantly observed in 30-40% of
      SCA1 patients without regard to the size of CAG repeats, while the frequency of
      nystagmus decreases with reduction in size of the CAG expansion. 

PMID- 24283688
TI  - Methylmalonic acid in serum from patients with neurological symptoms consistent
      with cobalamin deficiency.
AB  - Patients may have neurological symptoms due to cobalamin deficiency in spite of a
      normal plasma cobalamin level. The aim of the present study was to test if serum
      methylmalonic acid (S-MMA) can identify these cobalamin deficient patients.
      Patients with neurological symptoms consistent with cobalamin deficiency and
      normal plasma cobalamin had an estimation of S-MMA. If S-MMA was elevated,
      treatment with by droxycobalamin was offered. The patients were followed for one
      year in a prospective study with blood tests, clinical assessment and
      neurophysiological tests. Serum-MMA was above 0.37 MUmol/l (+2 SD of normal mean)
      in 15 out of 134 patients (11.2%) tested. Twelve of these patients were treated
      with hydroxycobalamin injections. A significant decrease in S-MMA below 0.37
      MUmol/l was found in 11 patients treated, indicating a functional cobalamin
      deficiency. Five patients were followed for one year. Documented improvement of
      neurological symptoms and nerve conduction velocity was shown in three of these
      patients. Of the remaining two patients treated one did not change and one
      deteriorated. S-MMA can identify patients with neurological symptoms due to
      cobalamin deficiency in spite of a normal plasma cobalamin level. 

PMID- 24283689
TI  - Chorea and high antiphospholipid antibodies: probable primary antiphospholipid
      syndrome.
AB  - A young man presented with generalized chorea as the first manifestation of
      probable primary antiphospholipid syndrome. He was well till 3 months before
      admission when he started to have involuntary, choreiform movements involving all
      extremities, the head and the bulbar muscles. Apart from these movements his
      physical examination was otherwise unremarkable. Laboratory investigations
      revealed mild thrombocytopenia, high partial thromboplastin time (PTT) only
      partially corrected by the addition of normal plasma, false positive syphilis
      serology, weakly positive antinuclear antibody and a high level of IgG
      anticardiolipin antibodies. Brain magnetic resonance imaging (MRI) showed
      multiple scattered small areas of high signal intensity on T2 weighted image in
      the area of centrum semiovale bilaterally. The patient was started on aspirin and
      prednisone with rapid symptomatic improvement. Despite the difficulty in proving
      the association between chorea and the high antiphospholipid antibodies, chorea
      appears in this case to be the initial symptom of primary antiphospholipid
      syndrome and we suggest screening for antiphospholipid antibodies in unexplained
      cases of chorea. 

PMID- 24283690
TI  - A clinical variance in familial amyotrophic lateral sclerosis with a point
      mutation in Cu/Zn superoxide dismutase gene.
AB  - We report here a novel point mutation in exon 5 of the Cu/Zn superoxide dismutase
      (SOD) gene resulting in an amino acid substitution of valine(148) by isoleucine
      (V148I) in a Japanese family with amyotrophic lateral sclerosis (FALS). In this
      family, the age at onset was young (28.0 +/- 3.8 years old, mean +/- SD, n = 4)
      and the disease progression was rapid (22.0 +/- 5.9 months, n = 3) with low Cu/Zn
      SOD activity (56.3 and 59.0% of the controls, n = 2). It is interesting that the
      clinical features of ALS varied very much among the affected members. One case
      had weakness of the lower extremities at first, and died without bulbar paresis.
      The second case first noticed wasting of the upper limbs with bulbar symptoms,
      but the third had weakness of upper extremities without developing dysarthria nor
      dysphagia until death. The living remainder first developed fasciculation of the
      tongue without weakness of extremities. The valine(148) is conserved among
      different species, and V148I mutation might destabilize dimer formation with
      another SOD subunit, leading to decrease enzymatic activity. These results
      suggested that there could be considerable clinical variance among the patients
      of FALS within one family, carrying the same Cu/Zn SOD mutation such as V148I. 

PMID- 24283691
TI  - Weber's syndrome due to a possible solitary brainstem toxoplasmosis as a
      presenting sign of AIDS.
AB  - We report the case of a young man, with a previous history of parenteral drug
      abuse, who developed a Weber's syndrome. Brain computed tomographic scan and
      nuclear magnetic resonance imaging showed a single ring enhancing lesion in the
      right mesencephalic site. After the demonstration of seropositivity for human
      immunodeficiency vims, a presumptive diagnosis of cerebral toxoplasmosis in an
      AIDS patient was made and a specific treatment was started. A partial
      neuroradiological and clinical improvement were obtained. Opportunistic cerebral
      lesions, as first manifestation of AIDS, should be always considered in subjects
      at risk for AIDS who present a brainstem syndrome. 

PMID- 24283692
TI  - Radiation-induced injury to the carotid artery: a longitudinal study.
AB  - Therapeutic radiation can lead to damage of arterial walls. In the present
      investigation, we studied prospectively 16 patients without pre-existing vascular
      disease (13 males, three females; mean age = 59.75 +/- 11.9 years) who had
      undergone surgery and post-operative radiation therapy (cumulative dose = 56.2 +/
      10.2 Gy) for the treatment of carcinoma of the head and neck. The carotid
      arteries were examined every 3 months for 19.9 +/- 8.7 months using Doppler
      ultrasound and B-mode sonography. The thickness of the arterial walls was
      determined using an index (outer:inner mean arterial wall), and it was compared
      to a group of age-matched control subjects (n = 16) with healthy arteries. The
      index of the common carotid artery (CCA) was initially 1.14 +/- 0.04 in both the
      right and left CCA in the radiation-treated subjects. By the end of the study,
      this index had increased significantly to 1.37  0.14 in both right and left CCA
      in the radiation-treated subjects (p < 0.01). There was a significant difference
      in arterial wall thickness between the radiation-treated and control subjects (p
      < 0.001). Frequent and extensive smooth-surfaced plaques indicative of arterial
      thickening in the area of the common carotid and internal carotid arteries were
      seen in the irradiated patients. Four patients developed > 50% atherosclerotic
      stenosis of the internal carotid artery. These data suggest that arterial damage
      may occur following radiation treatment of the head and neck area. Modification
      of radiation therapy for the post-surgical treatment of head tumors coupled with
      the continuous monitoring of the carotid arteries using B-mode sonography could
      minimize this arterial damage. 

PMID- 24283693
TI  - Interleukin-2, its soluble receptor, and soluble T8 antigen in acute ischemic
      stroke.
AB  - The treatment of neoplasia with interleukin-2 (IL-2) can be complicated by
      neurological deficits resembling transient Ischemic attack and stroke. We
      investigated whether interleukin-2 contributes to the natural course of
      cerebrovascular ischemia and particularly to the pathogenesis of infection
      associated stroke. Plasma levels of interleukin-2 were below the level of
      detectability in almost all measurements. Patients with and without previous
      infection (n = 11, 805 +/-445 U/ml vs n = 19, 824 +/- 501 U/ml) did not have
      significantly higher levels of soluble interleukin-2 receptors than control
      subjects with (n = 14, 667 +/- 229 U/ml) or without vascular risk factors (n =
      17, 567 +/- 176 U/ml). Receptor levels increased in patients during the first
      week after stroke (n = 15, 1157 +/- 1013, p < 0.02). Levels of soluble T8 antigen
      (sT8) were higher in patients (n - 26, 320 +/- 112 U/ml) than in healthy control
      subjects (n = 15, 246 +/- 92 U/ml; p < 0.05) and sT8 levels increased during the
      first week after stroke (p < 0.05). These results reflect an immunological
      response to the cerebral infarct; they do not indicate a general role of the IL-2
      system in the pathogenesis of ischemic stroke with or without previous infection.

PMID- 24283694
TI  - Dysmenorrhea and hyperventilation tetany and its management with carbamazepine.

PMID- 24283695
TI  - Neurological considerations about panic disorder.

PMID- 24283696
TI  - The prevalence of onychomycosis in the global population: a literature study.
AB  - BACKGROUND: Onychomycosis is a common disorder, and high prevalence figures are
      commonly cited in the literature. OBJECTIVES: Evaluate the prevalence of
      onychomycosis based on published studies. METHODS: Relevant studies were
      identified in Medline by using specific search criteria. RESULTS: Eleven
      population-based and 21 hospital-based studies were identified. The mean
      prevalence in Europe and North America was 4.3% [95% Confidence Interval (CI):
      1.9-6.8] in the population-based studies, but it was 8.9% (95% CI: 4.3-13.6) for
      the hospital-based studies. Both population-based and hospital-based studies
      showed that onychomycosis is more common in toenails and is seen more frequently
      in males. The main causative agent was a dermatophyte in 65.0% (95% CI: 51.9
      78.1) of the cases. Trichophyton rubrum was the single most common fungus and was
      cultured on average in 44.9% of the cases (95% CI: 33.8-56.0). Moulds were found
      on average in 13.3% (95% CI: 4.6-22.1) and yeasts in 21.1% (95% CI: 11.0-31.3).
      LIMITATIONS: We may not have been able to locate all studies. CONCLUSIONS:
      Onychomycosis is a common disorder, but it may not be as common as cited in the
      literature, because hospital-based studies might overestimate the prevalence of
      onychomycosis. It is more frequent in males, and toenails are more commonly
      affected. Dermatophytes, particularly T. rubrum, are the main causative agents.

PMID- 24283697
TI  - The impact of self-reported childhood trauma on emotion regulation in borderline
      personality disorder and major depression.
AB  - Early life stress is said to play a critical role in the development of
      borderline personality disorder (BPD) and major depressive disorder (MDD), but
      the underlying mediating factors remain uncertain. This study aimed to
      investigate self-reported childhood trauma, emotion regulation difficulties, and
      their associations in a sample of BPD (n = 49) and MDD (n = 48) patients and
      healthy control participants (n = 63). Multiple regressions were used to evaluate
      the impact of the quality and severity of self-reported childhood trauma on self
      reported emotion regulation. The results supported an association between self
      reported maltreatment experiences, especially emotional abuse and neglect, and
      emotion regulation difficulties. Additional analyses showed that emotion
      regulation difficulties influence the association between self-reported emotional
      abuse and acute symptomatology in the BPD subgroup. Emotion regulation
      difficulties may be 1 pathway through which early life stress, particularly
      emotional abuse, increases the risk for developing BPD symptomatology. 

PMID- 24283698
TI  - Epidermal growth factor receptor (EGFR) contributes to fetal lung fibroblast
      injury induced by mechanical stretch.
AB  - CONTEXT: Epidermal growth factor receptor (EGFR) is critical for normal fetal
      lung development. However, the role of this receptor in lung injury induced by
      mechanical ventilation is controversial. OBJECTIVE: To investigate in vitro
      whether EGFR plays a protective role or contributes to stretch-induced lung
      injury. METHODS: Fetal lung fibroblasts were isolated from wild-type and EGFR
      knockout mice and exposed to physiologic stretch (2.5% elongation) or injurious
      stretch (20% distention). Cells were evaluated for necrosis, apoptosis,
      proliferation and inflammation. RESULTS: Injurious stretch increased lactate
      dehydrogenase (LDH) release to similar degree in wild-type and knockout cells. In
      contrast, 20% stretch increased cleaved caspase-3 and decreased proliferating
      cell nuclear antigen (PCNA) only in wild-type cells. Furthermore, 20% stretch
      increased macrophage inflammatory protein-2 (MIP-2) and monocyte chemotactic
      protein-1 (MCP-1) by 3-5 fold in wild-type cells. In contrast, in knockout cells
      MIP-2 decreased by 50% and MCP-1 only increased by 60% when compared to
      physiologic stretch. CONCLUSION: Our data show a decrease of apoptosis and
      inflammation and absence of decreased proliferation after injurious stretch of
      fetal fibroblasts lacking EGFR. These data suggest that EGFR contributes to lung
      injury mediated by stretch. We speculate that EGFR may contribute to the arrest
      of lung development observed after mechanical ventilation by decreasing the
      population of lung fibroblasts.

PMID- 24283699
TI  - Properties of human brain sodium channel alpha-subunits expressed in HEK293 cells
      and their modulation by carbamazepine, phenytoin and lamotrigine.
AB  - BACKGROUND AND PURPOSE: Voltage-activated Na(+) channels contain one distinct
      alpha-subunit. In the brain NaV 1.1, NaV 1.2, NaV 1.3 and NaV 1.6 are the four
      most abundantly expressed alpha-subunits. The antiepileptic drugs (AEDs)
      carbamazepine, phenytoin and lamotrigine have voltage-gated Na(+) channels as
      their primary therapeutic targets. This study provides a systematic comparison of
      the biophysical properties of these four alpha-subunits and characterizes their
      interaction with carbamazepine, phenytoin and lamotrigine. EXPERIMENTAL APPROACH:
      Na(+) currents were recorded in voltage-clamp mode in HEK293 cells stably
      expressing one of the four alpha-subunits. KEY RESULTS: NaV 1.2 and NaV 1.3
      subunits have a relatively slow recovery from inactivation, compared with the
      other subunits and NaV 1.1 subunits generate the largest window current.
      Lamotrigine evokes a larger maximal shift of the steady-state inactivation
      relationship than carbamazepine or phenytoin. Carbamazepine shows the highest
      binding rate to the alpha-subunits. Lamotrigine binding to NaV 1.1 subunits is
      faster than to the other alpha-subunits. Lamotrigine unbinding from the alpha
      subunits is slower than that of carbamazepine and phenytoin. CONCLUSIONS AND
      IMPLICATIONS: The four Na(+) channel alpha-subunits show subtle differences in
      their biophysical properties, which, in combination with their (sub)cellular
      expression patterns in the brain, could contribute to differences in neuronal
      excitability. We also observed differences in the parameters that characterize
      AED binding to the Na(+) channel subunits. Particularly, lamotrigine binding to
      the four alpha-subunits suggests a subunit-specific response. Such differences
      will have consequences for the clinical efficacy of AEDs. Knowledge of the
      biophysical and binding parameters could be employed to optimize therapeutic
      strategies and drug development.

PMID- 24283700
TI  - Role of cold climate and freeze-thaw on the survival, transport, and virulence of
      Yersinia enterocolitica.
AB  - Surface and near-surface soils in cold climate regions experience low temperature
      and freeze-thaw (FT) conditions in the winter. Microorganisms that are of concern
      to groundwater quality may have the potential to survive low temperature and FT
      in the soil and aqueous environments. Although there is a body of literature on
      the survival of pathogenic bacteria at different environmental conditions, little
      is known about their transport behavior in aquatic environments at low
      temperatures and after FT. Herein, we studied the survival, transport, and
      virulence of a Gram-negative bacterial pathogen, Yersinia enterocolitica, when
      subjected to low temperature and several FT cycles at two solution ionic
      strengths (10 and 100 mM) in the absence of nutrients. Our findings demonstrate
      that this bacterium exhibited higher retention on sand after exposure to FT.
      Increasing the number of FT cycles resulted in higher bacterial cell surface
      hydrophobicity and impaired the swimming motility and viability of the bacterium.
      Moreover, the transcription of flhD and fliA, the flagellin-encoding genes, and
      lpxR, the lipid A 3'-O-deacylase gene, was reduced in low temperature and after
      FT treatment while the transcription of virulence factors such as ystA,
      responsible for enterotoxin production, ail, attachment invasion locus gene, and
      rfbC, O-antigen gene, was increased. Y. enterocolitica tends to persist in soil
      for long periods and may become more virulent at low temperature in higher ionic
      strength waters in cold regions. 

PMID- 24283701
TI  - Phase-controlled synthesis of Cu2ZnSnS4 nanocrystals: the role of reactivity
      between Zn and S.
AB  - Cu2ZnSnS4 (CZTS) nanocrystals with different morphologies and phases have been
      synthesized in hot organic solvents such as dodecanethiol and oleylamine. The
      crystallographic phases could be controlled by the sulfur precursor and the
      ligand species of the metal salts used for the synthesis. When a highly reactive
      sulfur precursor and metal acetates were used, wurtzite CZTS nanocrystals were
      obtained. On the other hand, using a low-reactivity sulfur precursor or metal
      chlorides produced CZTS nanocrystals in a kesterite phase. The experimental
      results from systematic investigations indicated that the reaction rate between
      Zn and S precursors played a determining role for the growth of CZTS nanocrystals
      with different crystalline phases. A relatively faster reaction between Zn and S
      precursors in comparison to the Sn-S reaction favored the formation of a
      metastable wurtzite phase, which could be accelerated by increasing the
      reactivity of the S precursor. This work provided a safe and economical way to
      synthesize high-quality phase-controlled Cu2ZnSnS4 nanocrystals, especially
      wurtzite nanorods, for potential photovoltaic applications. Moreover, preliminary
      results show that the proposed mechanism also applies to the phase-controlled
      synthesis of other quaternary Cu2MSnS4 (M = Cd(2+), Mn(2+)) nanocrystals. 

PMID- 24283702
TI  - Developmental haemostasis: age-specific differences in the quantity of hemostatic
      proteins: reply to a rebuttal.

PMID- 24283703
TI  - Preparation and physicochemical characteristics of polylactide microspheres of
      emamectin benzoate by modified solvent evaporation/extraction method.
AB  - Emamectin benzoate is highly effective against insect pests and widely used in
      the world. However, its biological activity is limited because of high resistance
      of target insects and rapid degradation speed in fields. Preparation and
      physicochemical characterization of degradable microcapsules of emamectin
      benzoate were studied by modified solvent evaporation/extraction method using
      polylactide (PLA) as wall material. The influence of different compositions of
      the solvent in internal organic phase and external aqueous phase on diameter,
      span, pesticide loading, and entrapment rate of the microspheres was
      investigated. The results indicated that the process of solvent extraction and
      the formation of the microcapsules would be accelerated by adding water-miscible
      organic solvents such as ethyl ether, acetone, ethyl acetate, or n-butanol into
      internal organic phase and external aqueous phase. Accelerated formation of the
      microcapsules would result in entrapment rates of emamectin benzoate increased to
      as high as 97%. In addition, by adding ethanol into the external aqueous phase,
      diameters would reduce to 6.28 MUm, whereas the loading efficiency of emamectin
      benzoate did not increase. The PLA microspheres prepared under optimum conditions
      were smoother and more spherical. The degradation rate in PLA microspheres of
      emamectin benzoate on the 10th day was 4.29 +/- 0.74%, whereas the degradation
      rates of emamectin benzoate in methanol solution and solid technical material
      were 46.3 +/- 2.11 and 22.7 +/- 1.51%, respectively. The PLA skeleton had
      combined with emamectin benzoate in an amorphous or molecular state by using
      differential scanning calorimetry (DSC) determination. The results indicated that
      PLA microspheres of emamectin benzoate with high entrapment rate, loading
      efficiency, and physicochemical characteristics could be obtained by adding water
      miscible organic solvents into the internal organic phase and external aqueous
      phase. 

PMID- 24283704
TI  - Stem cell factor SALL4, a potential prognostic marker for myelodysplastic
      syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases
      with variable clinical course. Predicting disease progression is difficult due to
      lack of specific molecular marker(s). SALL4 plays important roles in normal
      hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to
      acute myeloid leukemia (AML) transformation. However, the role of SALL4 in human
      MDS has not been extensively investigated. In this study, we evaluate the
      diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in
      a cohort of MDS patients. METHODS: Fifty-five newly diagnosed MDS, twenty MDS
      AML, and sixteen post-treatment MDS patients were selected for our study along
      with ten healthy donors. RESULTS: We demonstrated that SALL4 was over-expressed
      in MDS patients and proportionally increased in MDS patients with high grade/IPSS
      scores. This expression pattern was similar to that of Bmi-1, an important marker
      in predicting MDS/AML progression. In addition, the level of SALL4 was positively
      correlated with increased blast counts, high-risk keryotypes and increased
      significantly in MDS-AML transformation. Furthermore, higher level of SALL4
      expression was associated with worse survival rates and SALL4 level decreased
      following effective therapy. CONCLUSIONS: To the best of our knowledge, this is
      the largest series and the first to report the expression pattern of SALL4 in
      detail in various subtypes of MDS in comparison to that of Bmi-1. We conclude
      that SALL4 is a potential molecular marker in predicting the prognosis of MDS.

PMID- 24283705
TI  - The personality profile of young adults with delayed sleep phase disorder.
AB  - Delayed sleep phase disorder (DSPD) is a circadian rhythm sleep disorder
      characterized by a substantial delay in the major sleep period, resulting in
      difficulties falling asleep and awakening at a socially desirable time in the
      morning. This study is the first to investigate the NEO-Personality Inventory
      Revised profile of young adults with DSPD. The study includes 40 patients
      diagnosed with DSPD (mean age = 20.7) and 21 healthy controls (mean age = 21.1).
      Results showed that young adults with DSPD scored higher on Neuroticism, lower on
      Extroversion, and much lower on Conscientiousness than the control group.
      Assessing the personality profile of young adults with DSPD before initiating
      treatment might provide useful clinical guidance regarding the individual needs
      for follow up during treatment.

PMID- 24283706
TI  - Mechanisms, treatment and prevention of cellular injury and death from delayed
      events after aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: Subarachnoid hemorrhage (SAH) patients often develop brain injury
      as a result of a number of delayed complications, resulting in significant
      morbidity and mortality. Many of these complications arise due to delayed
      cerebral ischemia, which occurs secondary to the hemorrhage. AREAS COVERED: The
      mechanisms of the delayed injury are reviewed, including angiographic vasospasm,
      cortical spreading ischemia, small arteriolar constriction, microthromboemboli,
      free radical injury and inflammation. Some current and prospective therapies for
      SAH are discussed, in the context of these complications. Statins have been
      particularly promising in experimental studies. EXPERT OPINION: Multiple
      mechanisms are involved in the pathogenesis of the delayed insult after SAH. New
      drugs may need to target multiple pathways to injury. Trials aiming to treat
      complications after SAH could benefit from taking into account the multifactorial
      pathogenesis of delayed insults.

PMID- 24283707
TI  - Gemcitabine-induced radiation recall myositis in a patient with dermatomyositis.

PMID- 24283708
TI  - Improving the health status of minority women: overcoming the knowledge deficit.

PMID- 24283709
TI  - Ovarian reserve in systemic lupus erythematosus patients with normal menstrual
      cycles and in the absence of exposure to alkylating agents.

PMID- 24283711
TI  - Long-term survival for patients with metabolic syndrome after bioprosthetic or
      mechanical valve replacement.
AB  - BACKGROUND: Metabolic diseases are thought to negatively impact the long-term
      survival of cardiac patients and have been shown to be associated with reduced
      durability of bioprosthetic heart valves. The purpose of this study is to
      determine whether long-term survival of post-valve replacement patients is
      affected by the presence of metabolic disease, and whether choice of tissue
      versus mechanical prosthesis impacts survival. METHODS: A retrospective review
      was conducted of all isolated valve replacements performed between 2002 and 2011
      from the STS adult cardiac database of Emory Healthcare Hospitals. A total of
      1,222 cases were reviewed, of which 909 patients had AVR (661 tissue, 248
      mechanical), and 313 MVR (190 tissue, 123 mechanical). Cardiometabolic syndrome
      (CMS), in accordance with the World Health Organization (WHO) definition, was
      present in 242 of 1,222 (19.8%) cases in entire cohort, 203 of 909 (22.3%) in
      AVR, and 39 of 313 (12.5%) in MVR. Cox proportional hazard regression analysis
      was used to calculate long-term survival after adjusting for propensity score
      (PS), Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM), and
      direct covariates for valve and implant type and stratifying by CMS. RESULTS: In
      PS adjusted AVR, patients with CMS risk factors had worse survival compared to
      metabolic risk-free patients (AHR = 3.47), as was the case for MVR (AHR = 4.06).
      Tissue MVR patients with CMS had higher hazard of death compared to patients with
      no diabetes and no metabolic risk factors after adjusting for PROM (AHR = 3.33)
      and direct covariates (AHR = 3.91). CONCLUSIONS: Metabolic diseases negatively
      impact long-term survival of aortic and mitral valve replacement (MVR) patients.
      Tissue prostheses are associated with worse long-term survival following MVR.

PMID- 24283710
TI  - Subclinical impairment of ovarian reserve in systemic lupus erythematosus
      patients with normal menstruation not using alkylating therapy.
AB  - BACKGROUND: Disease activity is a major factor in menstrual disorders in systemic
      lupus erythematosus (SLE) patients not receiving alkylating therapy. However, the
      ovarian reserve of SLE women with normal menstruation is still unclear. METHODS:
      Twenty-three SLE patients naive to cytotoxic agents (SLE group) and nineteen SLE
      patients receiving current or previous cyclophosphamide (CTX) therapy (without
      other cytotoxic agents; SLE-CTX group) were enrolled. Twenty-one age-matched
      healthy women served as controls. All patients and controls had a regular
      menstrual cycle. Basal hormone levels, including follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone
      (AMH), and antral follicle count (AFC) were analyzed in the two study groups and
      compared with the control group. RESULTS: No significant differences were found
      between the SLE, SLE-CTX, and control groups in age, body mass index (BMI), and
      basal FSH and LH levels. The E2 (P=0.023) levels were high and the AMH (P=0.000)
      values and AFC (P=0.001) were significantly lower in the SLE and SLE-CTX groups
      compared to control. However, these values were similar between the SLE and SLE
      CTX groups. CONCLUSION: SLE patients not receiving alkylating therapy who had
      normal menstruation and short illness duration still had an impaired ovarian
      reserve.

PMID- 24283712
TI  - Transcriptomics to study the effect of a Mediterranean-inspired diet on
      inflammation in Crohn's disease patients.
AB  - BACKGROUND: Inflammation is an essential immune response; however, chronic
      inflammation results in disease including Crohn's disease. Therefore, reducing
      the inflammation can yield a significant health benefit, and one way to achieve
      this is through diet. We developed a Mediterranean-inspired anti-inflammatory
      diet and used this diet in a 6-week intervention in a Crohn's disease population.
      We examined changes in inflammation and also in the gut microbiota. We compared
      the results of established biomarkers, C-reactive protein and the micronuclei
      assay, of inflammation with results from a transcriptomic approach. RESULTS: Data
      showed that being on our diet for 6 weeks was able to reduce the established
      biomarkers of inflammation. However, using transcriptomics, we observed
      significant changes in gene expression. Although no single gene stood out, the
      cumulative effect of small changes in many genes combined to have a beneficial
      effect. Data also showed that our diet resulted in a trend of normalising the
      microbiota. CONCLUSIONS: This study showed that our Mediterranean-inspired diet
      appeared to benefit the health of people with Crohn's disease. Our participants
      showed a trend for reduced markers of inflammation and normalising of the
      microbiota. The significant changes in gene expression after 6 weeks highlighted
      the increased sensitivity of using transcriptomics when compared to the
      established biomarkers and open up a new era of dietary intervention studies.

PMID- 24283713
TI  - The influence of empowerment and incivility on the mental health of new graduate
      nurses.
AB  - AIM: To test a model based on Kanter's theory of structural empowerment, which
      examines the relationships between new graduate nurses' perceptions of structural
      empowerment, workplace incivility and mental health symptoms. BACKGROUND: The
      initial years of practice can be particularly stressful for new graduate nurses,
      who may be particularly vulnerable to uncivil behaviour as a result of their
      status in the work environment. Disempowerment and incivility in the workplace
      may compound the mental health symptoms experienced by new graduate nurses.
      METHOD: A predictive, non-experimental design was used to examine the
      relationship between structural empowerment, workplace incivility and mental
      health symptoms in a sample of new graduate nurses working in hospital settings
      in Ontario (n = 394). RESULT: High levels of structural empowerment were
      significantly associated with fewer negative mental health symptoms in new
      graduates. However, co-worker incivility and supervisor incivility partially
      mediated the effect of structural empowerment on new graduate nurses' mental
      health symptoms. CONCLUSION: The findings suggest that empowering workplaces
      contribute to lower mental health symptoms in new graduate nurses, an effect that
      is diminished by incivility. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies that
      foster empowering work conditions and reduce uncivil behaviour are needed to
      promote positive mental health in new graduate nurses.

PMID- 24283714
TI  - High-performance nanothermite composites based on aloe-vera-directed CuO
      nanorods.
AB  - In this work, we demonstrate the development of high-performance nanothermite
      composites derived from super-reactive CuO nanorods oxidizers fabricated by
      simple biogenic routes using Aloe vera plant extracts. Nanorods of various length
      scales have been realized via simple sonoemulsion and solid-state biosynthesis
      routes using Aloe vera gel as a green surfactant promoting the directional growth
      of CuO nanorods in both solid and emulsion phase. The biosynthesized CuO nanorods
      (oxidizers)/fuel (nanoaluminum) composites ignited vigorously with abundant gas
      generation, developing high heat of reaction of 1.66 kJ g(-1) and very high
      pressurization rate of around 1.09 MPa MUs(-1) and peak pressure of 65.4 MPa when
      blasted inside a constant volume pressure cell with a charge density of 0.2 g cm(
      3). The pressurization rates so obtained are four times higher with twice the
      peak pressure in comparison to such nanothermites formulated via other available
      state of the art wet-chemical techniques, which reflects the catalytic role of
      Aloe vera surface functional groups (A. vera-sfg) enhancing the reactivity of CuO
      oxidizers with excess gas release rate during exothermic reaction with
      nanoaluminum. Through this work, Aloe vera gel has for the first time been
      identified as a novel biotemplate for green synthesis of nanorod structures of
      metal oxides, and we have also studied the utility of A. vera-sfg in the creation
      of super-reactive CuO oxidizers producing excellent heat of reaction and dynamic
      pressure characteristics as demanded in propellants, explosives, and
      pyrotechnics. 

PMID- 24283715
TI  - Radiocontrast-induced thyroid dysfunction: is it common and what should we do
      about it?
AB  - There has been a substantial increase in the use of radiocontrast-enhanced
      imaging studies in the past two decades (particularly computed tomography and
      coronary angiography). Sudden exposure to high levels of iodide may result in
      thyroid dysfunction (hyperthyroidism and hypothyroidism alike). Although the
      adverse-event rate is not very high, the condition is notable considering the
      large number of contrast-enhanced radiographic studies performed. Clinicians
      often have to decide on the most suitable diagnostic modality and the safest
      contrast medium when it comes to certain patients. In this study, we stress that
      the thyroid function of the patients should also be taken into consideration
      while making such decisions. We discuss in detail the prevalence and types
      (hypothyroidism and hyperthyroidism) of radiocontrast-induced thyroid
      dysfunction. We list the subsets of the population that are at a higher risk of
      radiocontrast-induced thyroid dysfunction and summarize the necessary prophylaxis
      and possible treatment. The presented principles apply to intravenous, intra
      arterial and enteral (endoscopic retrograde cholangiopancreatography) routes of
      iodinated contrast medium administration. 

PMID- 24283716
TI  - Total arsenic in raw and boiled portions of Norway lobster (Nephrops norvegicus)
      from the central Adriatic Sea.
AB  - The distribution of total arsenic in different portions of Norway lobster
      (Nephrops norvegicus L., Crustacea) was studied both in fresh samples and after a
      boiling process. All individuals (n = 80) were selected of medium standard
      commercial size (13-15 cm). The highest mean concentrations (26.86 +/- 1.57 mg/kg
      wet weight (ww)) were found in the raw brown meat of the crustacean, probably due
      to its detoxification role, whereas the lowest mean values (15.97 +/- 0.85 mg/kg
      ww) were in the raw exoskeleton. The raw white meat reported mean values of 16.09
      +/- 0.61 mg/kg ww. The levels of arsenic contamination detected in the boiled
      portions showed a significant (p < 0.01) decrease compared to the raw portions,
      as a consequence of solubilization phenomena. In fact, a large amount of arsenic
      from raw lobsters was transferred to the corresponding boiling broth. In the most
      commonly consumed portion, the white meat, only slight losses (7.22%) in total
      arsenic content were observed compared to the raw portion.

PMID- 24283717
TI  - Deletion of thioredoxin-interacting protein preserves retinal neuronal function
      by preventing inflammation and vascular injury.
AB  - BACKGROUND AND PURPOSE: Retinal neurodegeneration is an early and critical event
      in several diseases associated with blindness. Clinically, therapies that target
      neurodegeneration fail. We aimed to elucidate the multiple roles by which
      thioredoxin-interacting protein (TXNIP) contributes to initial and sustained
      retinal neurodegeneration. EXPERIMENTAL APPROACH: Neurotoxicity was induced by
      intravitreal injection of NMDA into wild-type (WT) and TXNIP-knockout (TKO) mice.
      The expression of apoptotic and inflammatory markers was assessed by
      immunohistochemistry, elisa and Western blot. Microvascular degeneration was
      assessed by periodic acid-Schiff and haematoxylin staining and retinal function
      by electroretinogram. KEY RESULTS: NMDA induced early (1 day) and significant
      retinal PARP activation, a threefold increase in TUNEL-positive nuclei and 40%
      neuronal loss in ganglion cell layer (GCL); and vascular permeability in WT but
      not TKO mice. NMDA induced glial activation, expression of TNF-alpha and IL-1beta
      that co-localized with Muller cells in WT but not TKO mice. In parallel, NMDA
      triggered the expression of NOD-like receptor protein (NLRP3), activation of
      caspase-1, and release of IL-1beta and TNF-alpha in primary WT but not TKO Muller
      cultures. After 14 days, NMDA induced 1.9-fold microvascular degeneration, 60%
      neuronal loss in GCL and increased TUNEL-labelled cells in the GCL and inner
      nuclear layer in WT but not TKO mice. Electroretinogram analysis showed more
      significant reductions in b-wave amplitudes in WT than in TKO mice. CONCLUSION
      AND IMPLICATIONS: Targeting TXNIP expression prevented early retinal ganglion
      cell death, glial activation, retinal inflammation and secondary
      neuro/microvascular degeneration and preserved retinal function. TXNIP is a
      promising new therapeutic target for retinal neurodegenerative diseases.

PMID- 24283718
TI  - The role of PD-1 and PD-L1 in T-cell immune suppression in patients with
      hematological malignancies.
AB  - T-cell activation and dysfunction relies on direct and modulated receptors. Based
      on their functional outcome, co-signaling molecules can be divided as co
      stimulators and co-inhibitors, which positively and negatively control the
      priming, growth, differentiation and functional maturation of a T-cell response.
      We are beginning to understand the power of co-inhibitors in the context of
      lymphocyte homeostasis and the pathogenesis of leukemia, which involves several
      newly described co-inhibitory pathways, including the programmed death-1 (PD-1)
      and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1
      and PD-L1 biological functions and their alterative expression in hematological
      malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the
      potential for immunotherapy via blocking PD-1 and PD-L1 in hematological
      malignancies are also reviewed. 

PMID- 24283720
TI  - Arterial mechanisms in the pathophysiology of migraine headache-implications for
      modern therapy.
AB  - Studies of the cephalic vascular system have markedly contributed towards an
      understanding of the mechanisms of migraine pain. Whereas cerebral blood flow
      changes, and thereby changes in the arterioles, correlate poorly with migraine
      headache, abnormal regulation of the large cranial arteries seems to play a
      significant role in relation to migraine pain. Thus, vasodilation of extra- and
      intracranial conductance arteries has been described both during spontaneous
      migraine attacks and during experimentally provoked vascular headaches. Whether
      dilation of these arteries is the key mechanism of migraine nociception or is
      merely associated with another more important nociceptive mechanism remains to be
      shown. Studies of vascular regulatory mechanisms have not only pointed towards a
      possible locus of migraine pain, but have also been helpful in demonstrating a
      new molecular mechanism of migraine-the key effect of the small messenger
      molecule nitric oxide. It is likely that nitric oxide is the most important
      molecule responsible for the induction of migraine attacks. 

PMID- 24283721
TI  - European Stroke Prevention Study 2: A study of low-dose acetylsalicylic acid and
      of high dose dipyridamole in secondary prevention of cerebro-vascular accidents.
AB  - In spite of some data being added to our knowledge of the effect of antiplatelets
      in secondary prevention of brain ischemic lesion in recent years, the main
      reasons to perform a second European Stroke Prevention Study (ESPS 2), which
      started in 1987-1988, were: (a) clarify the relative roles of aspirin (ASA) and
      dipyridamole (DP) alone or in combination; (b) confirm the efficacy of small
      doses of ASA and, so doing, decrease the number of drop-outs due to ASA side
      effects; (c) join information to the effect of antiplatelets in complete stroke.
      General characteristics of the sample of 6602 patients are presented and compared
      with other major trials and series. The patients in the four treatment arms
      (aspirin, dipyridamole, aspirin + dipyridamole and placebo) are compared. The
      more relevant features and risk factors known to influence long term prognosis
      are described and discussed. The small proportion of patients included with TIA
      (23.7%) and the comparability among treatment groups are stressed. No relevant
      differences have been found, among groups, on the sex or age distribution,
      prevalence of hypertension, diabetes, previous vascular events or atrial
      fibrillation, nor in the characteristics of the accident leading to the inclusion
      in trial. 

PMID- 24283722
TI  - Abnormalities of carnitine metabolism in chronic fatigue syndrome.
AB  - Carnitine may be involved in the pathogenesis of the chronic fatigue syndrome
      (CFS). However, no information about the cellular metabolism of carnitine in CFS
      patients is currently available. Therefore, we aimed to measure the levels of
      carnitine (total, free and short-chain) in both peripheral blood lymphocytes
      (PBLs) and sera from patients with CFS. The serum levels of total, free and short
      chain were comparable in CFS patients, considered as the whole group, to those in
      healthy control subjects, even though a trend indicating slightly reduced serum
      concentrations of free carnitine was observed in male patients with CFS. In
      contrast, the concentrations of total, free and short-chain carnitine in PBLs
      from patients with CFS were significantly lower than in cells from healthy
      controls. Our study indicates that patients with CFS require exogenous carnitine
      supplementation. The low carnitine concentrations in PBLs from patients with CFS
      probably reflect the carnitine deficiency occurring in other tissues, including
      the skeletal muscles. The low cellular concentrations of carnitines may help to
      explain both the immunological abnormalities and the impaired energy metabolism
      in skeletal muscles. 

PMID- 24283719
TI  - Trends in the incidence of type 1 diabetes among Jews and Arabs in Israel.
AB  - OBJECTIVE: To assess the trends in the incidence of type 1 diabetes between 1997
      and 2010 among 0-17-yr-old Israeli Jews and Arabs compared with global trends.
      METHODS: Data on children with newly diagnosed type 1 diabetes reported by
      pediatric endocrinologists from 19 medical centers to the Israel Center for
      Disease Control, as part of the National Diabetes Register. RESULTS: During 1997
      2010, 2857 Jews and 757 Arabs were diagnosed with type 1 diabetes. The average
      age-adjusted incidence among Jews was higher than Arabs [12.2 per 100 000, 95%
      confidence interval (CI) 10.5-14.2 and 8.9 per 100 000, 95% CI 7.5-10.7, p =
      0.0001, respectively], however, the annual percent change was higher for Arabs
      compared with Jews (4.0 vs. 3.6%, p = 0.005, respectively). The mean age at
      diagnosis was similar for Jews and Arabs (9.6 +/- 4.4 vs. 9.9 +/- 4.4 yr, p =
      0.08), and it remained stable during 1997-2010 in both ethnic groups (p = 0.6).
      In both Jews and Arabs the highest annual percent change was observed in younger
      children. It was 4.9% for children aged 5-9 yr and 10.7% for children aged 0-4
      yr, respectively. There were no differences in the frequency of diabetic
      ketoacidosis (DKA) between Jews (39.9%) and Arabs (41.3%), (p = 0.5). CONCLUSION:
      Type 1 diabetes incidence of Jews and Arabs in Israel is increasing. The
      incidence is higher in Jews than in Arabs; however, the annual percent change is
      higher in Arabs than in Jews. In both Ethnic groups the incidence of type 1
      diabetes is increasing especially among young children.

PMID- 24283723
TI  - Frequency and relevance of IgM intrathecal synthesis in multiple sclerosis.
AB  - Using a new ELISA method we have measured the IgM concentration in the serum and
      the cerebrospinal fluid CSF from 110 neurological patients. Among there, 41 had
      multiple sclerosis (MS), 48 other inflammatory diseases (OID), including 30 AIDS,
      and 21 non-inflammatory neurological diseases (NID). A highly significant
      correlation was established between results with native IgM and the
      dithiothreitol reduced IgM. An intrathecal synthesis (ITS) of IgM was detected
      using the CSF IgM/CSF albumin ratio, the IgM index and a quantitative formula in
      33 patients: nine MS, 23 OID (including 18 AIDS) and one NID. The frequency of
      IgM ITS was 22% in MS patients, 48% in the OID (60% in AIDS) and 5% in the NID
      groups. This ITS was not impaired by an increase in serum IgM concentration or by
      a blood-CSF barrier damage. These facts confirm that intrathecal immunity is not
      a "steady-state" related to the general immunity but a specific response
      restricted to the central nervous system. Conversely, CSF IgM increase and IgM
      ITS were closely related (p < 10(-6) ). In addition, IgM ITS and IgG ITS were
      found to be highly correlated in OID, especially in AIDS patients: such
      correlation was not observed in the MS group. No significant correlations were
      observed between IgM ITS and any of the clinical parameters in MS patients. These
      results suggest the probable specificity of IgM ITS in MS patients. 

PMID- 24283724
TI  - The pathophysiology of parkinsonism in multiple system atrophy.
AB  - Parkinsonism is the principal motor disorder of multiple system atrophy (MSA). In
      order to explore the pathophysiology of parkinsonism in MSA, we analysed 182
      pathological reports from the literature and 35 from the United Kingdom
      Parkinson's Disease Society Brain Bank, and have also examined published post
      mortem and in vivo neurochemical data. This review indicates that the brains of
      MSA patients who had parkinsonism in life show degeneration principally in
      anatomically related regions of the nigrostriatal dopaminergic pathway and of the
      striatum as well as in the globus pallidus. This degeneration affects both
      "direct" and "indirect" striatal outflow pathways. The degree of dopaminergic
      response in any one subject at any one point in the evolution of the disease
      probably relates both to the severity and extent of striatal pathology and also
      to the balance between degeneration in "indirect" and "direct" striatal outflow
      pathways and in the pallidum, especially its external part Abnormal
      oligodendroglial cytoplasmic inclusions are also found in large numbers in most
      of the basal ganglia structures that show cell loss and gliosis. The precise
      consequences of their additional presence in motor cortex remain unknown, but
      disturbance of function in supplementary motor area could also contribute to the
      extrapyramidal syndrome of MSA. 

PMID- 24283725
TI  - Long-term beneficial effects of adrenal medullary autografts supported by nerve
      growth factor in Parkinson's disease.
AB  - Parkinson's disease has been the object of several therapeutic strategies based
      upon replacement of the degenerating dopaminergic neurons. Adrenal medullary
      transplants were tried initially, because of the biochemical relationship between
      chromaffin cells of the medulla and dopaminergic neurons of the substantia nigra.
      Compared to transplant of fetal neurons, autologous grafts of adrenal medullary
      tissue has the advantage of using a readily available source of tissue without
      the problems of immunosuppression. However, these cells have not proven to be as
      effective as fetal neurons, probably because they do not fully differentiate into
      neurons. In animal models, brief treatment with nerve growth factor can
      facilitate such differentiation. This study is a clinical evaluation of the
      efficacy of adrenal medullary cell transplantation, combined with nerve growth
      factor infusion. Two patients were selected who were moderately to severely
      affected (Hoehn-Yahr stage 2 in on-phase and stage 4 in off-phase). After
      adrenalectomy, small pieces of medulla were prepared and implanted
      stereotactically into the dorsal putamen on one side of the brain. A catheter
      filled with mouse beta-nerve growth factor (NGF) was placed close to the grafts.
      Infusion of NGF was continued for one month. Despite a progressively
      deteriorating course prior to surgery, both patients showed improvement on the
      rating scales postoperatively. There was also significant improvement in timed
      motor tests. Motor readiness evoked potentials showed increased voltage over the
      operated hemisphere. The study points to methods and feasibility of supplying
      nerve growth factor intraparenchymally to the human brain. Possible implications
      with respect to other growth factors, particularly Glial cell-line Derived
      Neurotrophic factor (GDNF) are discussed. 

PMID- 24283726
TI  - A prospective study of depression in French patients with Parkinson's disease.
      The Depar study.
AB  - To investigate the prevalence and symptomatology of depression in Parkinson's
      disease (PD), we have studied 506 unselected patients attending the neurology
      services in French general hospitals during a 5 month period defined for
      prospective inclusion. 246 patients (48.6%) were suspected of depression
      according to different methods of evaluation and 168 (33.2%) were defined as
      definite or probable depression. According to the Montgomery and Asberg scale, 46
      cases (9%) had a severity score suggestive of major depression. As a function of
      the cut-off score defined for severity, these patients represented from 23.2 to
      43.7% of the depressive population with PD. There was no significant difference
      between depressed and non depressed PD patients as a function of the patient's
      current age or age at onset of PD. A significantly higher rate of depression was
      found among women with PD. A past history of depression was a risk factor for
      mood disorder after onset of PD. The severely depressed patients had a
      significantly longer duration of PD and a higher score of cognitive impairment
      than mildly or moderately depressed and non depressed patients with PD. Depressed
      patients had a significantly more advanced stage of disability than non-depressed
      patients with PD. 

PMID- 24283727
TI  - Multiple cerebral hemorrhages as a possible complication of antiblastic treatment
      with cyclophosphamide, methotrexate and fluoruracil (CMF) for breast cancer.
AB  - In this paper we describe the case of a patient who underwent left breast radical
      mastectomy and corresponding removal of her axillary lymphonodes, for an
      infiltrating lobular cancer with massive colonizing (16 of 19 lymphonodes
      examined), stage T2N2M0. During chemotherapy with cyclophosphamide, methotrexate
      and 5 fluoruracil (CMF), the patient presented a symptomatology characterized by
      anarthria and dysphagia. These symptoms were the consequences of multiple
      cerebral hemorrhages unrelated to alterations in the coagulation process. The
      temporal relation with the pharmacological treatment and the lack of other
      explanations of the induced phenomenon lead us to hypothesize a cytotoxic
      mechanism due to the CMP treatment. 

PMID- 24283728
TI  - Molecular biology and genetics of Alzheimer's disease.
AB  - The recent progress in molecular biology research has changed the past concepts
      on Alzheimer's disease (AD) and other nervous system amyloidoses. This paper
      compiles the basic principles of molecular biology of AD and reviews their
      clinical impact The new data about the function and metabolism of amyloid
      precursor protein and the more recent information on the role of the
      apolipoprotein E have provided new insight into the pathogenesis of this disease.
      Although further investigations are still required to assemble these data into a
      theory that completely explains the development of the disease and changes the
      present symptomatic therapeutic strategies to an entire preventive or curative
      approach, the recent research results in this field are relevant for the
      diagnostic and therapeutic management of AD patients. 

PMID- 24283729
TI  - A Japanese family with Machado-Joseph disease characterized by initial emaciation
      and myoclonus.
AB  - We describe a Japanese family with hereditary spinocerebellar ataxia
      characterized by initial emaciation and myoclonus. The proband first noted
      truncal ataxia, myoclonus in the shoulder and general emaciation at age 24. The
      other affected members of the family also had such emaciation in the early stage
      of the disease. The DNA analyses of the family revealed that the patients of the
      family are associated with the expansions of CAG repeats for Machado-Joseph
      disease (MJD) on the long arm of chromosome 14. Although the clinical features of
      MJD are very variable, general emaciation in an early stage of the disease and
      systemic myoclonus have not been documented. Because it is sometimes difficult to
      distinguish among hereditary spinocerebellar ataxias such as spinocerebellar
      ataxia type 1 (SCA1) or dentatorubropallidoluysian atrophy (DRPLA) by clinical
      features, a genetic examination provides better understanding of such a rare and
      ambiguous type of hereditary spinocerebellar ataxia. 

PMID- 24283730
TI  - Deep cerebral venous thrombosis presenting as acute amnestic syndrome.
AB  - A 45 year-old man presented with a rapid onset of memory impairment Brain
      computed tomography showed multiple abnormal low density areas in the deep
      cerebral white matter. Magnetic resonance imaging revealed bilateral thalamic
      infarcts and extensive thrombosis of the vein of Galen and the straight sinus,
      which was confirmed by cerebral angiography. The only potential cause was protein
      S deficiency. Heparin therapy was started only after the occurrence of a
      pulmonary embolism. The outcome was excellent Deep cerebral venous thrombosis
      must be considered as a possible cause of amnestic syndrome. Clinical awareness
      and early use of anticoagulation may alter the usual fatal outcome. 

PMID- 24283731
TI  - Epidermal growth factor receptor and p53 protein expression in human
      glioblastomas.
AB  - p53 mutations and amplification of epidermal growth factor receptor (EGFR) gene
      are the most frequently detected genetic alterations in glioblastomas; thus,
      these changes seem to delineate two subgroups of glioblastomas: those originated
      de novo and those originated from preexistent low grade astrocytomas. Paraffin
      embedded surgical specimens of 30 human glioblastomas were analyzed
      immunohistochemically for the presence of p53 protein and EGFR. Approximately
      half of the cases were p53 protein-positive while one-third were EGFR positive.
      Only three cases were positive for both p53 protein and EGFR. There was no
      difference between the average ages of patients with only-p53-positive, and
      double-negative tumors, while three glioblastomas with both p53 protein and EGFR
      immunopositivity occured in older patients (mean age 67.0 years, p < 0.02).
      Patients with only-EGFR-positive tumors were younger, but not significantly (44.3
      years, p < 0.1). This study supports the notion that there are two main
      subpopulations of glioblastoma-with EGFR and with p53 protein overexpression. 

PMID- 24283732
TI  - The accessory nerve repetitive nerve stimulation test: a valuable second-line
      test in myasthenia gravis.
AB  - The diagnostic usefulness of the accessory nerve repetitive nerve stimulation
      (RNS) test was evaluated in 100 patients with myasthenia gravis (MG). The test
      was easy to perform and reliable at the low rates of stimulation. A higher
      diagnostic sensitivity was found in the accessory nerve RNS test than in the
      ulnar nerve RNS test on either the abductor digiti quinti or flexor carpi ulnaris
      muscles, especially in mild generalized MG. Diagnostic sensitivity was
      significantly increased when RNS test results for three muscles were combined,
      especially in mild generalized MG and sero-positive MG. In a small number of
      cases only the ulnar or accessory nerve RNS test was abnormal. There was a good
      correlation between electrophysiological and clinical severity of MG in the
      accessory nerve RNS test Thus, we conclude that the accessory nerve RNS test is a
      valuable second-line test and its greatest usefulness is in cases of mild
      generalized MG. 

PMID- 24283733
TI  - Cough syncope with hypertension-caused by brainstem compression?
AB  - The commonly accepted pathophysiological changes in cough syncope include a fall
      in systemic blood pressure, raised intracranial pressure and cerebral ischemia.
      However, cases of cough syncope without hypotension have been reported in
      patients with the Arnold-Chiari malformation. We describe a 48-year old man with
      cough syncopes. Constant blood pressure monitoring revealed hypertension instead
      of the expected hypotension during the episodes. Attacks of loss of consciousness
      were associated with motor phenomena, i.e. tonic posturing and tonic spasm.
      Magnetic resonance imaging revealed compression and displacement of the medulla
      oblongata by an ectatic and elongated vertebral artery. The commonly accepted
      mechanism of cough syncope cannot explain the symptoms in our patient because a
      fall of blood pressure was lacking. Instead, a cough-induced compression of the
      displaced brainstem may have caused a transient dysfunction of the reticular
      formation. 

PMID- 24283734
TI  - Lamotrigine use in twelve patients with the Lennox-Gastaut Syndrome.
AB  - This brief report describes the effects of lamotrigine on 12 patients with the
      Lennox-Gastaut Syndrome in an open, uncontrolled study. Three patients are
      seizure free and five others substantially improved. Seven of these eight
      patients have shown a marked improvement in quality of life. Lamotrigine is an
      extremely useful adjunct in the management of the Lennox-Gastaut Syndrome. 

PMID- 24283735
TI  - Candida parapsilosis vertebral osteomyelitis.
AB  - A case of culture verified Candida parapsilosis lumbar spondylodiscitis, with
      infectious involvement of an aortic prosthetic graft, presented with a lumbar
      radicular pain syndrome. Only 33 Candida infections of the spine are described in
      the literature. Candida parapsilosis was cultured in three cases. Considering the
      poor general condition of the patient, a conservative treatment with bedrest,
      casting and amphotericin B, hydrocortisone and itraconazol was given. The patient
      died 28 months after onset from intercurrent pneumonia. 

PMID- 24283736
TI  - Hydrocephalus complicating chronic Borrelia burgdorferi meningitis.

PMID- 24283737
TI  - [The current technical possibilities of the peroperative safety advancement in
      the microsurgery of cerebral aneurysms - a review article].
AB  - The authors present the technical aspects of perioperative safety during the
      microsurgery of cerebral aneurysms. We evaluated the advantages and disadvantages
      of the microvascular Doppler ultrasonography, the intraoperative digital
      subtraction angiography, the intraoperative transit time flowmetry, the
      intraoperative monitoring - motor evoked potentials and somatosensory evoked
      potentials, and the ICG videoangiography. The authors, based on their own
      experience, recommend combining different methods to eliminate the weak points of
      the individual specific methods. Combining the ICG with the flowmetry and the
      motor evoked potentials enhances safety during the surgery of cerebral aneurysms
      with the resultant reduction of the perioperative morbidity/mortality.

PMID- 24283738
TI  - [Liver and pulmonary metastases of the colorectal carcinoma - the experience of
      the Department of Surgery, University Hospital in Pilsen].
AB  - INTRODUCTION: Liver and pulmonary metastases of the colorectal carcinoma develop
      in about 20-70%, resp. in 10-22% patients with the colorectal carcinoma. Their
      treatment is still a matter of discussion. The aim of our study was to evaluate
      the results of surgical treatment as a part of the multimodal approach. MATERIAL
      AND METHODS: 30 patients with liver and pulmonary colorectal metastases were
      operated on between 2002 and 4/2013. The average age was 62.8 +/- 10.7 years. 19
      patients had metachronous and 11 synchronous metastases. The liver metastases
      preceded pulmonary in 14 cases, and vice versa in 5 patients. Both types of
      metastases developed in seven patients simultaneously. Liver resection was
      performed in 23, radiofrequency ablation (RFA) in 7 patients. Laser pulmonary
      metastasectomy was performed in 15, pulmonary resection in 14 and RFA in one
      patient. The liver procedure preceded pulmonary in 25 patients. 73.3% patients
      had adjuvant oncological treatment. RESULTS: 30 days mortality rate was 3.3%
      (N=1) for the actinomycotic sepsis complicated with MRSA infection. Morbidity
      rate was 10%. Recurrence of liver metastases developed in 6 patients. RFA was
      performed in all patients. The median of overall and disease free survival was
      6.9, resp. 1.1 years. CONCLUSION: Surgical treatment as a part of the multimodal
      treatment is the only radical treatment for patients with liver and pulmonary
      metastases. It offers good long-term results.

PMID- 24283739
TI  - [Intraarticular arthrodesis of the unstable lumbosacral spine - first results of
      the prospective study].
AB  - INTRODUCTION: The aim of this study is the presentation of surgical treatment of
      the unstable lumbosacral (LS) spine using the bilateral intraarticular facet
      fusion. MATERIAL AND METHODS: For surgical treatment patients were indicated with
      the degenerative instability of LS spine. We examined VAS (Visual Analogue
      Scale), ODI (Oswestry Disability Index), static and dynamic skiagrams and
      magnetic resonance imaging before surgery. Laminectomy for the decompression of
      the spinal stenosis and a transpedicular (TP) fixation were performed.
      Corticospongious bone chips from lamina were inserted into the intraarticular
      caves after the drilling of the facet cartilages. The study group consisted of 17
      patients (the average age of 66 years), with a minimal follow-up of two years.
      One year after the surgery, we evaluated VAS, ODI, the improvement of walking
      distance, Odom criteria, complications, the stability of the spinal segment and
      the extent of the intraarticular fusion using Computed Tomography (CT). RESULTS:
      VAS for the axial pain was decreased from 6.8 (in average) before surgery to 1.5
      (in average) after one year; the improvement was by 77.4%. VAS for the radicular
      pain was decreased from 6.3 (in average) before surgery to 1.6 (in average) one
      year after surgery; the improvement was by 74.6%. ODI was decreased from 52.1 (in
      average) before surgery to 23.4 (in average) one year after surgery; the
      improvement was by 55.1%. According to Odom criteria we evaluated 10 patients as
      excellent and 7 patients as good one year after surgery. The bone intraarticular
      fusion and the stability of the spinal segment according to CT scans and dynamic
      skiagrams were concluded in all patients (100%). The extent of the intraarticular
      fusion (facet area) according to CT scans was 89% in average. All patients
      improved their walking distance and there were no surgical complications.
      CONCLUSION: The intraarticular arthrodesis of LS spine was concluded in all
      (100%) patients during one year after surgery. After the concomitant laminectomy,
      the TP fixation and the intraarticular fusion of the unstable segment of LS spine
      we observed a decrease of the axial pain by 77%, the radicular pain by 75% and
      the improvement of functional ability by 55% in comparison to the status before
      surgery. According to the author this surgical method is safe, cheep, and
      effective in certain indications of degenerative disease of LS spine, at the same
      time.

PMID- 24283740
TI  - [Smoking and postoperative complications].
AB  - INTRODUCTION: Smoking has a negative impact on the outcome of surgical
      procedures. Smoking leads to higher risk of postoperative complications and it
      delays wound healing. MATERIALS AND METHODS: We observed pulmonary complications,
      wound healing complications, and the length of the postoperative hospitalization
      period of 877 patients admitted for elective surgery.. Patients were divided
      according to their smoking status in to 3 groups: the current smokers were 32%
      (279/877), the former smokers 31% (274/877) and the non-smokers 37% (324/877).
      RESULTS: Pulmonary complications occurred more frequently in the smoking group
      (3.9%) compared to the non-smoking group (0.9%), p<0,001. The incidence of wound
      infections was 7.5% in the smoking group compared to 4.6% in the non-smoking
      group. Wound dehiscence occurred in 3.6% patients in the smoking group,
      respectively 2.8% in the non-smoking group, without statistical significance. The
      number of postoperative hospitalisation days was 3 days for both smokers and non
      smokers, but it decreased inversely to number of smoke-free days before the
      surgery for those who stopped smoking: those abstinent for 31-90 days were
      hospitalized for 7.0 days, those abstinent for 91-183 were hospitalized for 5.5
      days, and for those abstinent over 184 days the postoperative hospitalization
      was, again, 3 days. Among the current smokers, 93% preferred to stay smoke-free
      after the surgery. CONCLUSIONS: Our results support better surgery outcomes for
      non-smokers. However, our sample was not large enough to assess the impact of the
      number of preoperative smoke-free days. An elective surgery seems to be an unused
      occasion to motivate smokers to stop smoking, preferably, as soon as possible
      before the surgery date.

PMID- 24283741
TI  - [Rare complication after stapled hemorrhoidectomy].
AB  - Statistics show that more than half of the population suffers from hemorrhoids at
      different clinical stages. Only a small percentage of them (5 to 10%) require
      surgical treatment. The gold standard is open hemorrhoidectomy (most commonly
      Milligan-Morgan operation). Circular stapled hemorrhoidopexy by Longo is an
      alternative to conventional hemorrhoidectomy. The main advantages of this
      procedure are: less postoperative pain, earlier return to work and to social
      life. The complication rate is similar to open hemorrhoidectomy. This method,
      however, also brings new kinds of complications, some of them potentially life
      threatening. Our case report presents one of these rare complications.

PMID- 24283742
TI  - [Recurrent subareolar non puerperal abscess of breast with fistules of
      lactiferous ducts (Zuskas disease)].
AB  - INTRODUCTION: Zuskas disease (ZD) is an illness also known as the recurrent
      subareolar non-puerperal abscess of breast with fistulas of lactiferous ducts or
      as a periductal mastitis. ZD is rare, but painful chronic disease of breast
      characterized by local inflammation and evacuation of viscous content from
      abscess around the nipple. We present a rare form of the non-puerperal mastitis
      in patients with recurrence of this disease and with the description of
      management and treatment. CONCLUSION: The treatment of ZD is often inadequate and
      it leads to the recurrence of ZD and retraction of the nipple. Definitive
      treatment of ZD is surgical excision of the fistulation, removing of whole
      retroareolar fibroglandular tissue, abscess cavity and ductal tissue inside the
      nipple, including the obstructed ducts. The ratio of patients cured by this
      method is high, as well as their satisfaction with the final cosmetic effect of
      the nipple and breast.

PMID- 24283743
TI  - [Acceptable risks in surgery from the perspective of the evidence-based medicine
      and an evaluation of the quality of surgical care].
AB  - A qualified assessment of the risks of surgical treatment and especially
      operations is based on the evaluation of morbidity, mortality and long-term
      results of surgeons work. These analyses should be conducted based on the
      principles of the evidence-based medicine (EBM) and, in recent years, an
      assessment of the risks that surgical treatment has been included into a broader
      complex of evaluating the quality of surgical care. Surgery, other surgical
      specializations, and the urgent medicine belong among medical fields which most
      often carry a risk of unsuccessful outcomes and complications. Taking into
      account the complexity of medicine, the diagnostic and therapeutic processes are
      burdened necessarily by a certain number of complications. It is never possible
      to completely eliminate human errors, but what is possible is to continuously
      decrease their numbers and repair them on time. EBM is defined as a method of
      treating for patients based on the best scientific evidence resulting from
      clinical and epidemiological scientific research publications. From an EBM
      perspective, surgery compared with pharmaceutical treatment is usually at a
      disadvantage because the studies with the highest level of evidence (the
      controlled randomized studies) are usually not possible to be performed in
      surgery. In various situations it is only possible to obtain certain kinds of
      evidence and in surgery the highest level of evidence is most often obtained from
      cohort studies and case control studies as a possible means of sorting our
      information. Currently, evaluating the quality of surgical care should be in the
      forefront of interest of every surgeon. Traditional criteria include the
      evaluation of operative and postoperative complications, mortality, the number of
      re-operations, the evaluation of the satisfaction of the patient with the
      procedure performed, the length of survival of oncological patients, the number
      of recurrences and a number of other criteria. The term "High Volume Hospital"
      represents a newly developing concept of evaluating quality in surgery, which
      arises from the assumption that with the increasing number of procedures
      (operations) performed the quality of the results attained increases as well. The
      evaluation of quality in surgery is a topic which should be addressed more
      thoroughly among surgeons. The creation of indicators of quality of surgical care
      and their application into clinical practice has great significance for the
      development of surgery and it is not possible to leave it beyond the control of
      surgeons.

PMID- 24283744
TI  - [Complications and risks of the surgery of tumors of the upper digestive tract
      (Foregut) Part I: Esophagus].
AB  - INTRODUCTION: The aim of the work is to evaluate acceptable mortality and
      morbidity associated with the esophageal resections for carcinoma. METHOD: The
      work analyses the data of patients with esophageal cancer from the Czech National
      Cancer Registry and it compares personal experience with complications and risks
      associated with the esophagectomy for carcinoma with the data from specialized
      literature published in recent years. RESULTS: Despite improvements in the
      surgical technique and the perioperative intensive care, the esophagectomy
      maintains a relatively high morbidity and mortality. Published studies present
      mortality up to 10% and total morbidity between 40-60%. Respiratory complications
      are most frequent and significant and they reach up to 40% and the anastomotic
      dehiscence ranges from 0 to 25%. At the authors workplace in Novy Jicin, a total
      of 193 patients with the esophageal carcinoma were examined since 2007; 38% of
      these patients were indicated for operation and 62 esophageal resections with
      replacement were performed. The postoperative mortality within 30 days was 3.2%
      and the total morbidity was approximately 50%. Respiratory and cardiac
      complications were 28% and 18% respectively, fistula in the cervical anastomosis
      was seen in 5% and in the gastric tube in 3%, only one patient died from this
      surgical complication. The paralysis of the recurrent nerve occurred in 10%, and
      chylothorax in 3%. In almost all patients, the operation began with a
      laparoscopic revision to confirm operability and in 37% of the operated patients
      a video-assisted approach was used, most often the thoracoscopic mobilization of
      the esophagus. CONCLUSION: The surgical treatment of tumors of the esophagus is a
      highly specialized domain of thoracic surgeons specialized in the issuesof the
      esophagus. General trends for improving the morbidity and mortality include the
      use of minimally-invasive approaches, fast-track programs after the
      esophagectomy, and the application of principles of High-volume centres. The long
      term prognosis of patients with esophageal cancer is principally dependent on the
      degree of advancement of the disease.

PMID- 24283745
TI  - [Complications and risks in the surgery of tumors of the upper digestive tract
      (Foregut) Part II : Stomach].
AB  - INTRODUCTION: The aim of the work is to evaluate acceptable mortality and
      morbidity associated with stomach resections for carcinoma. METHOD: The work
      analyzes data of patients with gastric cancer from the Czech National Cancer
      Registry and compares personal experience with complications and risks associated
      with stomach resections for carcinoma with the data from specialized literature
      from recent years. RESULTS: The incidence of gastric cancer in the Czech Republic
      is presently 15.1/100 000 inhabitants, the mortality 11.6 and the prevalence
      48.3. Stomach resections for carcinoma are complicated operations. Despite
      improving surgical techniques and tactics, as well as the perioperative intensive
      care, this procedure remains associated with significant morbidity and mortality.
      At the Department of Surgery of the Oncological Center and Hospital Novy Jicin,
      286 patients with gastric cancer were operated between the years 2005 and 2012.
      In the group of 172 radical R0 resections, the mortality was 3.5% and the total
      morbidity was 33.7%. The most frequent and significant postoperative surgical
      complications were the pancreatitis (4.7%) and the anastomotic dehiscence (3.5%).
      The most frequent non-surgical ones were respiratory complications (4.7%). The
      mortality and morbidity frequency is comparable with the data published in
      specialized literature. Surgical treatment also utilized laparoscopy. All
      operations began with a diagnostic laparoscopy to specify the stage of the
      disease and to select the laparoscopic approach, most often a laparoscopically
      assisted resection, which was used in 60 patients (30%). Laparoscopy was
      preferred even for the palliative anastomoses. No significant differences in
      morbidity and mortality were seen between open and laparoscopic procedures and
      statistical analysis is planned to gain greater experience. CONCLUSION: In the
      Czech Republic, surgical treatment of tumors of the stomach is currently
      performed at a large number of workplaces with a low frequency. General trends
      for improving the morbidity and mortality include the use of minimally-invasive
      approaches, a fast-track program, and the application of principles of High
      volume centres. The long-term prognosis of patients with gastric cancer is
      principally dependent on the degree of advancement of the disease.

PMID- 24283746
TI  - Expression of human beta-defensin-2 in psoriatic epidermis models treated with
      balneophototherapy.
AB  - BACKGROUND: The molecular mechanisms of action of salt water soaks combined with
      ultraviolet (UV) irradiation--balneophototherapy (BPT)--are unknown. OBJECTIVES:
      We aimed to investigate the effect of BPT on the expression of human beta
      defensin-2 (hBD2) using a psoriatic epidermis model (PEM). METHODS: Using real
      time RT-PCR and ELISA, we studied the expression patterns of hBD2 in PEM which
      were treated over three consecutive days with differently concentrated salt water
      solutions [(3% NaCl; 30% NaCl, 30% Dead Sea salt (DSS)] and consecutive
      narrowband UVB exposure. RESULTS: mRNA of hBD2 was significantly reduced in
      irradiated 3% NaCl, 30% NaCl and 30% DSS soaked PEM when compared with non
      irradiated PEM. ELISA for hBD2 revealed significantly reduced protein expression
      in irradiated 3% NaCl, 30% NaCl and 30% DSS soaked PEM when compared with non
      irradiated PEM. Compared with irradiated controls and 3% NaCl soaked and
      irradiated PEM, BPT using 30% NaCl and 30% DSS revealed significantly decreased
      hBD2 protein levels. CONCLUSIONS: Both mono-treatment with salt water soaks and
      BPT of PEM result in altered expression of hBD2, whereas the effects observed are
      most prominent after BPT. hBD2 gene and protein expression is predominantly down
      regulated following BPT indicating that this combined phototherapeutic regimen is
      superior to mono-UVB or salt water soaks alone with respect to normalization of
      hBD2 expression in psoriatic epidermis.

PMID- 24283747
TI  - Selected gastrointestinal cancer presentations from the American Society of
      Clinical Oncology annual meeting 2013 in review: it is not about the destination,
      it is about the journey.
AB  - INTRODUCTION: In the GI tumors area, key findings from the American Society of
      Clinical Oncology 2013 annual meeting were long awaited, particularly in
      colorectal, gastric and pancreatic cancer. AREAS COVERED: The following pages
      briefly present and comment on a selection of those studies considered most
      relevant for clinical practice and future research planning. The following trials
      were then reviewed: the FIRE-3, Triplet + beva (TRIBE), new EPOC, CAIRO-3 and
      SAKK in colorectal cancer, the TRIO-013/LOGIC and COUGAR-02 in gastric cancer and
      the metastatic adenocarcinoma of the pancreas (MPACT) and LAP07 in pancreatic
      cancer. EXPERT OPINION: Although the proportion of clinical questions that these
      trials were able to answer was almost exactly paralleled by the introduction of
      new questions to be responded in the next (hopefully) few years, globally they
      represented a significant improvement in our knowledge about colorectal cancer
      and pancreatic tumors.

PMID- 24283748
TI  - Developmental hemostasis: age-specific differences in the levels of hemostatic
      proteins: a rebuttal.

PMID- 24283749
TI  - Structure and kinetics of fatty acid Langmuir monolayers on zinc salt solutions.
AB  - The adsorption of zinc cations under behenic acid Langmuir monolayers was
      investigated by means of isotherm measurements, grazing incidence X-ray
      diffraction and Brewster angle microscopy. The structure of the films was
      characterized as a function of Zn(2+) concentration, for three different
      counterions (chloride, iodide, bromide) and at two subphase pHs (5.5 and 7.5). At
      pH 5.5 and in the studied concentration range, Zn(2+) adsorption leads to a
      condensation of the fatty acid monolayer with the same phase transitions as over
      pure water. In contrast, at higher pH the organic X-phase is evidenced
      immediately above a concentration threshold without any ion organization. Even
      though Cu(2+) and Zn(2+)cations induce both the fatty acid X-phase, the kinetics
      of its formation appears strongly different. Indeed, as for Mg(2+) and Cd(2+),
      the intermediate new I-structure is evidenced in the course of Zn(2+) adsorption
      although superstructures are observed only for Mg(2+) and Cd(2+). However, for
      Zn(2+), the I-phase evolves to the final state through a new structure called X'
      and a continuous X'-X transition. Finally, any effect of the counterion is
      evidenced neither during the kinetic process nor in the final state. 

PMID- 24283750
TI  - Dissociative identity disorder among adolescents: prevalence in a university
      psychiatric outpatient unit.
AB  - The aim of this study was to determine the prevalence of dissociative identity
      disorder (DID) and other dissociative disorders among adolescent psychiatric
      outpatients. A total of 116 consecutive outpatients between 11 and 17 years of
      age who were admitted to the child and adolescent psychiatry clinic of a
      university hospital for the 1st time were evaluated using the Adolescent
      Dissociative Experiences Scale, adolescent version of the Child Symptom Inventory
      4, Childhood Trauma Questionnaire, and McMaster Family Assessment Device. All
      patients were invited for an interview with the Structured Clinical Interview for
      DSM-IV Dissociative Disorders (SCID-D) administered by 2 senior psychiatrists in
      a blind fashion. There was excellent interrater reliability between the 2
      clinicians on SCID-D diagnoses and scores. Among 73 participants, 33 (45.2%) had
      a dissociative disorder: 12 (16.4%) had DID, and 21 (28.8%) had dissociative
      disorder not otherwise specified. There was no difference in gender distribution,
      childhood trauma, or family dysfunction scores between the dissociative and
      nondissociative groups. Childhood emotional abuse and family dysfunction
      correlated with self-reported dissociation. Of the dissociative adolescents,
      93.9% had an additional psychiatric disorder. Among them, only separation anxiety
      disorder was significantly more prevalent than in controls. Although originally
      designed for adults, the SCID-D is promising for diagnosing dissociative
      disorders in adolescents, its modest congruence with self-rated dissociation and
      lack of relationship between diagnosis and childhood trauma and family
      dysfunction suggest that the prevalence rates obtained with this instrument
      originally designed for adults must be replicated. The introduction of diagnostic
      criteria for adolescent DID in revised versions of the Diagnostic and Statistical
      Manual of Mental Disorders, Fifth Edition, would refine the assessment of
      dissociative disorders in this age group. 

PMID- 24283751
TI  - Sleep in high-functioning children with autism: longitudinal developmental change
      and associations with behavior problems.
AB  - Sleep disturbance is common in autism spectrum disorder (ASD), but longitudinal
      trajectories are poorly defined. This study measured sleep disturbance at
      baseline and 1 year later examining change over time and associated problem
      behaviors. Participants were 84 gender-matched children, aged between 7 and 12
      years at baseline; 46 children were diagnosed with ASD, and 38 were typically
      developing (TYP) children. Parent reports on a range of scales were collected.
      The ASD group had more sleep disturbance than the TYP group. Sleep disturbance
      decreased over the year in children with ASD, but not in TYP children. Reduced
      sleep disturbance was associated with improved social ability. Sleep disturbance
      at baseline predicted later anxiety. Findings indicated different trajectories of
      sleep disturbance in ASD, and the implications are discussed. 

PMID- 24283753
TI  - The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine
      dinucleotide biosynthesis, is potentialized when used in combination with anti
      CD20 antibody.
AB  - APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis
      that exhibits potent anti-lymphoma activity. Rituximab (RTX), an anti-CD20
      antibody, kills lymphoma cells by direct apoptosis and antibody- and complement
      dependent cell-mediated cytotoxicities, and has clinical efficacy in non-Hodgkin
      cell lymphomas. In the present study, we evaluated whether RTX could potentiate
      APO866-induced human B-lymphoma cell death and shed light on death-mediated
      mechanisms associated with this drug combination. We found that RTX significantly
      increases APO866-induced death in lymphoma cells from patients and lines.
      Mechanisms include enhancement of autophagy-mediated cell death, activation of
      caspase 3 and exacerbation of mitochondrial depolarization, but not increase of
      reactive oxygen species (ROS) production, when compared with those induced by
      each drug alone. In vivo, combined administration of APO866 with RTX in a
      laboratory model of human aggressive lymphoma significantly decreased tumor
      burden and prolonged survival over single-agent treatment. Our study demonstrates
      that the combination of RTX and APO866 optimizes B-cell lymphoma apoptosis and
      therapeutic efficacy over both compounds administered separately.

PMID- 24283752
TI  - Lysine and arginine content of proteins: computational analysis suggests a new
      tool for solubility design.
AB  - Prediction and engineering of protein solubility is an important but imprecise
      area. While some features are routinely used, such as the avoidance of extensive
      non-polar surface area, scope remains for benchmarking of sequence and structural
      features with experimental data. We study properties in the context of
      experimental solubilities, protein gene expression levels, and families of
      abundant proteins (serum albumin and myoglobin) and their less abundant
      paralogues. A common feature that emerges for proteins with elevated solubility
      and at higher expression and abundance levels is an increased ratio of lysine
      content to arginine content. We suggest that the same properties of arginine that
      give rise to its recorded propensity for specific interaction surfaces also lead
      to favorable interactions at nonspecific contacts, and thus lysine is favored for
      proteins at relatively high concentration. A survey of protein therapeutics shows
      that a significant subset possesses a relatively low lysine to arginine ratio,
      and therefore may not be favored for high protein concentration. We conclude that
      modulation of lysine and arginine content could prove a useful and relatively
      simple addition to the toolkit available for engineering protein solubility in
      biotechnological applications. 

PMID- 24283754
TI  - Increased expression of costimulatory molecules CD86 and sCTLA-4 in patients with
      acute lymphoblastic leukemia.
AB  - We herein evaluate the role of the B7-family molecule CD86 and the Cytotoxic T
      lymphocyte-associated antigen-4 (CTLA-4) as a possible immunopathogenic factors
      in patients with ALL. The results of 60 patients with de novo ALL were compared
      to 40 controls. A significant statistical difference between CD86 expression and
      sCTLA-4 levels in patients versus their controls has been detected. During follow
      up period of 28 months, patients suffered from relapse (16 patients) had
      significantly higher CD86 expression and sCTL-4 levels compared to those remained
      in complete remission (44 patients) (p = 0.005 and 0.03 respectively). Patients
      who died from the disease (9 patients) showed significantly higher CD 86
      expression and sCTLA-4 levels than surviving patients (51 patients) (p = 0.004
      and 0.01 respectively). In conclusion, the higher levels of sCTLA-4 and CD86 in B
      ALL patients might be candidate parameters for poor prognosis and may serve to
      refine treatment stratification with intensification of therapy in those patients
      prone to relapse.

PMID- 24283755
TI  - Acute myeloid leukemia with DNMT3A mutations.
AB  - Acute myeloid leukemia (AML), a type of blood cancer, is characterized by an
      increase in the number of abnormal white blood cells in the bone marrow,
      frequently causing hematopoietic insufficiency. It is a heterogeneous disease
      featuring cytogenetic aberrations, recurrent somatic mutations and alterations in
      gene expression. DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) is closely
      associated with epigenetic modifications in mammalian development and disease.
      More recent studies have identified recurrent somatic mutations in DNMT3A in AML,
      most of which are heterozygous. The DNMT3A R882 codon is a mutational hotspot.
      The frequency of DNMT3A mutations varies among different countries, but mutations
      have been found to be associated with cytogenetics, age, white blood cell (WBC)
      count, prognosis and response of patients to chemotherapy. The normal function of
      DNMT3A can be disrupted by these mutations, which subsequently results in an
      abnormality of epigenetic modification. These data suggest that mutations in the
      DNMT3A gene represent a novel class of mutations in AML with distinct biological
      and clinical features. Further studies are needed to elucidate the exact
      molecular mechanism and function of DNMT3A mutations in leukemogenesis.

PMID- 24283756
TI  - Therapeutic options for patients with lymphoma and liver dysfunction or failure
      during mechlorethamine shortage.
AB  - Liver dysfunction in patients with lymphoma presents an important clinical
      dilemma because it limits the use of anthracyclines and vinca alkaloids for this
      potentially curable malignancy. Patients are typically treated with
      corticosteroids, rituximab and the nitrogen mustard mechlorethamine, and then
      transitioned to definitive therapy after improvement in liver function. Between
      2010 and 2012 mechlorethamine was not available and other strategies were
      required. In this case series, we describe seven cases of patients with lymphoma
      and liver dysfunction successfully treated in this time period with
      ifosfamide/carboplatin or gemcitabine/cisplatin.

PMID- 24283757
TI  - Increased risk for bone loss in women with systemic sclerosis: a comparative
      study with rheumatoid arthritis.
AB  - AIM: To assess bone mass in women with systemic sclerosis (SSc) in comparison to
      age and sex-matched patients with rheumatoid arthritis (RA), and to evaluate
      factors influencing bone mineral density (BMD). METHODS: Patients were
      consecutively recruited and assessed for BMD at the lumbar spine and hip by dual
      energy X-ray absorptiometry (DEXA) using a densitometer. In SSc, the extent of
      skin involvement, modified Rodnan skin thickness score (mRSS) and Medsger disease
      severity index were assessed. RESULTS: Forty-three patients with SSc and 38 age
      matched patients with RA were included. There was no difference in BMD
      measurements between patients with diffuse or limited SSc. Patients with SSc had
      similar risk factors associated with osteoporosis (OP) or low bone mass except
      for low body mass index (BMI) and low vitamin D levels compared to patients with
      RA. Lumbar spinal BMD and T score were similar between groups. Total hip and
      femoral neck BMD and T score at femoral neck and total hip were significantly
      lower in patient with SSc versus RA. There was significant association between
      mRSS, Medsger severity score (peripheral vascular involvement and skin) and
      femoral BMD. CONCLUSION: There is an increased risk for bone loss in patients
      with SSc and the risk of OP is associated with disease severity, prolonged
      menopause and disease duration. The complex pathophysiology of bone metabolism as
      well as complex pathogenesis of the SSc pose some difficulty reaching clear-cut
      conclusions on the causal relationship between SSc and bone loss.

PMID- 24283758
TI  - Prevalence of tobacco smoking among school teachers in Botswana.
AB  - BACKGROUND: Tobacco is a leading cause of death worldwide, and nearly 80% of all
      smokers live in low to middle income countries. Previous research has suggested
      that smoking rates vary by occupation, with relatively low rates commonly seen
      among educators. Despite this fact, little is known about the smoking habits of
      teachers in Botswana. The objective of this study, therefore, was to investigate
      prevalence and correlates of tobacco use among school teachers in Botswana.
      RESULTS: The prevalence of smoking among school teachers in Botswana was found to
      be relatively low. Of the 1732 participants in the study, only 3.2% reported
      being current smokers, 5.3% were ex-smokers and 91.5% had never smoked. Smoking
      was more common among male teachers when compared to females, being 10.8% and
      0.4%, respectively. Factors such as school level, marital status and body mass
      index were found to be positively associated with tobacco smoking, whereas age,
      length of employment and weekly working hours were not. CONCLUSION: This study
      suggests that Botswana school teachers have a low prevalence of tobacco smoking.
      While this result may be attributed to tobacco control measures that have been
      put in place, there is still need to put in place systems to monitor compliance
      and programs to help those who want to quit smoking. Such protocols would
      represent a major step forward in further reducing the prevalence of smoking in
      the education profession.

PMID- 24283759
TI  - Right ventricular outflow tract obstruction by a pedunculated cardiac hemangioma:
      a rare case of syncope.

PMID- 24283760
TI  - Donor risk index predicts graft failure reliably but not post-transplant
      infections.
AB  - BACKGROUND: The Donor Risk Index (DRI) is used to predict graft survival
      following liver transplantation, but has not been used to predict post-operative
      infections in graft recipients. We hypothesized that lower-quality grafts would
      result in more frequent infectious complications. METHODS: Using a prospectively
      collected infection data set, we matched liver transplant recipients (and the
      respective allograft DRI scores) with their specific post-transplant infectious
      complications. All transplant recipients were organized by DRI score and divided
      into groups with low-DRI and high-DRI scores. RESULTS: We identified 378 liver
      transplants, with 189 recipients each in the low-DRI and high-DRI groups. The
      mean DRI scores for the low- and high-DRI-score groups were 1.14+/-0.01 and
      1.74+/-0.02, respectively (p<0.0001 for the difference). The mean Model for End
      Stage Liver Disease (MELD) scores were 26.25+/-0.53 and 24.76+/-0.55,
      respectively (p=0.052), and the mean number of infectious complications per
      patient were 1.60+/-0.19 and 1.94+/-0.24, respectively (p=0.26). Logistic
      regression showed only length of hospital stay and a history of vascular disease
      as being associated independently with infection, with a trend toward
      significance for MELD score (p=0.13). CONCLUSION: We conclude that although DRI
      score predicts graft-liver survival, infectious complications depend more heavily
      on recipient factors.

PMID- 24283761
TI  - In vitro antimicrobial activity of fibrin sealants containing antimicrobial
      agents.
AB  - BACKGROUND: Antimicrobial prophylaxis is required to prevent surgical site
      infections (SSIs). However, it is difficult to maintain prolonged antimicrobial
      activity in the surgical incision. Fibrin sealants are used primarily for
      hemostasis, suture support, or the adhesion of tissues. The aim of this study was
      to develop fibrin sealants that exhibit antimicrobial activity due to the
      addition of an antimicrobial agent. METHODS: We determined the potencies and
      activities of cefazolin, ampicillin-sulbactam, vancomycin, teicoplanin, and
      arbekacin eluted from fibrin sealants. The antimicrobial activity was evaluated
      using methicillin-resistant Staphylococcus aureus (MRSA), multi-drug-resistant
      Pseudomonas aeruginosa (MDRP), and multi-drug-resistant Acinetobacter baumannii
      (MDRAB), which are the major pathogens responsible for hospital-acquired
      infections. RESULTS: Each antimicrobial agent eluted continuously from the fibrin
      clots for approximately two weeks. All eluates from fibrin clots containing
      antimicrobial agents maintained antimicrobial activity against MRSA for at least
      7 d. The eluates from fibrin clots containing ampicillin-sulbactam inhibited the
      growth of both MDRP and MDRAB for at least 5 d. CONCLUSION: Our data suggest that
      the addition of an antimicrobial agent to fibrin sealants is a useful method to
      prevent SSIs caused by bacteria, including antimicrobial-resistant strains.

PMID- 24283762
TI  - Febrile infection in post-prostate biopsy: results of a ten-year single
      institution study in South Taiwan.
AB  - BACKGROUND: Post-biopsy infection is one of the major concerns of urologists and
      patients for prostate biopsy. Many efforts have been made to reduce the infection
      rate. We conducted a study at a single institution with the goal of describing
      the bacteriology and incidence trends of febrile infections following trans
      rectal ultrasound (TRUS)-guided biopsy of the prostate. MATERIALS AND METHODS:
      From January 1998 to December 2002 (Period 1 of the study), January 2003 to
      August 2005 (Period 2), September 2005 to October 2007 (Period 3), and November
      2007 to December 2009 (Period 4), 1,406 patients underwent prostate biopsy at our
      hospital. All biopsies were conducted under TRUS guidance without preparation by
      enemas. Several steps were taken to reduce infectious complications following
      biopsy, including a shift to levofloxacin prophylaxis starting from Period 3 of
      our study and thorough instructions in post-biopsy self-care starting from the
      beginning of Period 4. The incidence and bacteriology of urinary tract infection
      (UTI) following the prostate biopsies were reviewed from chart records. RESULTS:
      Twenty-eight of 514 (5.4%), 13 of 276 (4.7%) nine of 274 (3.2%), and three of 342
      (0.9%) patients had post-biopsy febrile infections during the four periods of the
      study, respectively. Fifteen of 28 (53.5%), four of 13 (30.8%), five of nine
      (55.6%), and zero of three patients, respectively, had positive cultures of
      blood, urine, or both during the four study periods. Escherichia coli was the
      pathogen isolated most commonly and ampicillin- and fluoroquinolone-resistant
      strains of this organism were identified at a high frequency. The times to onset
      of fever after biopsy in the four study periods were 1.5+/-1.3 d, 3.7+/-2.7 d,
      2.2+/-1.6 d, and 2.5+/-0.9 d, respectively. CONCLUSIONS: Ampicillin- and
      fluoroquinolone-resistant strains of E. coli were the uropathogenic bacteria
      identified most commonly after prostate biopsy at our hospital. The incidence of
      UTI following prostate biopsy can be reduced by explaining instructions for
      medication and self-care thoroughly to patients undergoing such biopsy.

PMID- 24283763
TI  - Clostridium ramosum bacteremia: case report and literature review.
AB  - BACKGROUND: Clostridium ramosum is a common enteric anaerobe but infrequently
      also a cause of pathologic infection. METHODS: Case report and literature review.
      RESULTS: We reviewed 12 case reports describing infection with C. ramosum. When
      pathogenic, C. ramosum is cultured most commonly from the inner ear, anaerobic
      blood samples, or abscesses. Patients with such infections fall into two
      demographic groups, consisting of young children with ear infections or
      immunocompromised adults with bacteremia. Resistance of C. ramosum to antibiotics
      is uncommon. CONCLUSION: Clostridium ramosum is a common but generally commensal
      bacterial species. Rarely, it becomes pathogenic in young children or
      immunosuppressed adults.

PMID- 24283764
TI  - Bacterial adherence to different meshes used in abdominal surgery.
AB  - BACKGROUND: We studied the influence of morphology and type of material of
      abdominal wall prostheses in the avoidance of bacterial adhesion in acute and
      chronic mesh infections. METHODS: Three different types of prostheses were
      compared: 1) High-density polypropylene monofilament mesh (PMM); 2) low-density
      PMM; and 3) prostheses composed of low-density polypropylene and a non-porous
      hydrophilic film (composite prostheses). Microbial adhesion tests were performed
      using reference strains of Staphylococcus aureus 15981, Staphylococcus
      epidermidis ATCC 35984, Mycobacterium abscessus DSM 44196, and Mycobacterium
      fortuitum ATCC 13756 using a protocol described previously. RESULTS: Both
      Staphylococcus spp. and M. fortuitum strains showed lower adherence to PMM.
      Mycobacterium abscessus also exhibited lower adherence to composite prostheses.
      Both Mycobacterium spp. strains had lower adherence than Staphylococcus spp.
      strains for all materials except for low-density PMM. Mycobacterium fortuitum
      showed higher adherence to composite prostheses than M. abscessus, whereas the
      latter species had higher adherence to high-density PMM than M. fortuitum.
      CONCLUSION: Depending on the type of bacteria, collagen-coated hydrophilic
      prostheses with a large surface increased bacterial adherence significantly.
      These differences should be taken into consideration when choosing a mesh graft,
      which limits infection in abdominal wall reconstruction.

PMID- 24283765
TI  - Does primary closure increase surgical site infection after intestinal stoma
      reversal? A retrospective cohort study.
AB  - BACKGROUND: This study was undertaken to test the veracity of the hypothesis that
      primary incision closure after intestinal stoma reversal in adult patients is
      associated with a greater risk of surgical site infection (SSI) than are open
      incisions. METHODS: A retrospective cohort study was conducted at the Surgical
      Department of the Aga Khan University Hospital, Karachi, Pakistan. The study
      included adult patients who underwent elective loop and double-barreled
      intestinal stoma (ileostomy or colostomy) reversal through peristomal incisions
      between January 2005 and May 2011. Files were reviewed independently by two
      surgeons to establish main exposure (closed or open surgical sites) and outcome;
      i.e., SSI based on U.S. Centers for Disease Control and Prevention criteria.
      RESULTS: Sample size calculation prior to the study required 71 patients to be
      included in each exposure arm. Patients with closed surgical sites were
      relatively younger (mean 36+/-15 [standard deviation] years) than those with open
      surgical sites (41+/-15 years), with a male preponderance in both groups. Fifteen
      patients were found to have SSI: 3/71 (4.2%) in open and 12/71 (16.9%) in closed
      incisions. The risk of SSI in closed surgical sites was 5.8 times greater than in
      open sites (95% confidence interval for relative risk 1.5-22.5) after adjusting
      for gender, body mass index (BMI), site of stoma, malignant disease, and
      preoperative chemo-radiotherapy. CONCLUSION: The risk of SSI in closed incisions
      is greater than that in open incisions. It is suggested that incisions not be
      closed primarily in patients undergoing stoma reversal.

PMID- 24283766
TI  - Male first-line managers' experiences of the work situation in elderly care: an
      empowerment perspective.
AB  - AIM: To describe male first-line managers' experiences of their work situation in
      elderly care. BACKGROUND: First-line managers' work is challenging. However, less
      attention has been paid to male managers' work situation in health care.
      Knowledge is needed to empower male managers. METHOD: Fourteen male first-line
      managers were interviewed. The interview text was subjected to qualitative
      content analysis. RESULT: Work situations were described as complex and
      challenging; challenges were the driving force. They talked about 'Being on one's
      own but not feeling left alone', 'Having freedom within set boundaries', 'Feeling
      a sense of satisfaction and stimulation', 'Feeling a sense of frustration' and
      'Having a feeling of dejection and resignation'. CONCLUSION: Although the male
      managers report deficiencies in the support structure, they largely experience
      their work as a positive challenge. IMPLICATIONS FOR NURSING MANAGEMENT: To meet
      increasing challenges, male first-line managers need better access to supportive
      structural conditions. Better access to resources is needed in particular,
      allowing managers to be more visible for staff and to work with development and
      quality issues instead of administrative tasks. Regarding organisational changes
      and the scrutiny of management and the media, they lack and thus need support and
      information from superiors.

PMID- 24283767
TI  - Room temperature synthesis of a copper ink for the intense pulsed light sintering
      of conductive copper films.
AB  - Conducting films are becoming increasingly important for the printed electronics
      industry with applications in various technologies including antennas, RFID tags,
      photovoltaics, flexible electronics, and displays. To date, expensive noble
      metals have been utilized in these conductive films, which ultimately increases
      the cost. In the present work, more economically viable copper based conducting
      films have been developed for both glass and flexible PET substrates, using
      copper and copper oxide nanoparticles. The copper nanoparticles (with copper(I)
      oxide impurity) are synthesized by using a simple copper reduction method in the
      presence of Tergitol as a capping agent. Various factors such as solvent, pH, and
      reductant concentration have been explored in detail and optimized in order to
      produce a nanoparticle ink at room temperature. Second, the ink obtained at room
      temperature was used to fabricate conducting films by intense pulse light
      sintering of the deposited films. These conducting films had sheet resistances as
      low as 0.12 Omega/? over areas up to 10 cm(2) with a thickness of 8 MUm. 

PMID- 24283768
TI  - Clinical efficacy of a West African sorghum bicolor-based traditional herbal
      preparation Jobelyn shows increased hemoglobin and CD4+ T-lymphocyte counts in
      HIV-positive patients.
AB  - OBJECTIVES: The purpose of this study was to evaluate a traditional herbal
      preparation, Jobelyn,(r) for its effects on anemia and CD4+ T-cell counts in
      human immunodeficiency virus-positive (HIV+) patients in Nigeria. DESIGN: An open
      label pilot study involving 10 confirmed (HIV+) patients who were not receiving
      antiretroviral therapy (ARVT) was performed, in which the patients consumed
      Jobelyn for 8 weeks, at a dose of 500 mg twice daily. The pilot study was
      followed by a controlled trial involving 51 patients, all confirmed HIV+, where
      the patients with CD4+ T-cell counts below 350 cells/MUL were receiving ARVT. The
      eight patients with baseline CD4+ T-cell counts above 350 cells/MUL received
      Jobelyn. The remaining patients who all received ARVT were randomized to ARVT
      alone versus ARVT+Jobelyn for 12 weeks. RESULTS: Patients receiving ARVT showed a
      statistically significant improvement in their CD4+ T-cell counts across the 12
      week study period (p<0.01). Patients receiving ARVT+Jobelyn showed a faster
      improvement, reaching a high level of statistical significance compared to
      baseline already at 6 weeks (p<0.001), and remained highly significant at 12
      weeks (p<0.001). CONCLUSIONS: This is the first controlled study conducted to
      evaluate efficacy of Jobelyn on immune status in HIV+ patients. The data suggest
      that consumption of Jobelyn contributed to improved hemoglobin levels and
      increased CD4+ T-cell counts in Nigerian HIV+ patients. Further studies are
      needed to examine similar effects in other populations, and to elaborate on the
      underlying mechanisms, specifically, whether the consumption of Jobelyn supported
      multiple aspects of bone marrow function.

PMID- 24283769
TI  - Incidence of venous thromboembolism in different ethnic groups: a regional direct
      comparison study.
AB  - BACKGROUND: There are few studies that directly compare the variation in
      incidence of venous thromboembolism (VTE) according to ethnicity. OBJECTIVE: The
      aim of this study was to compare the rates of VTE, deep venous thrombosis (DVT)
      and pulmonary embolism (PE) among different ethnic groups. METHOD: The cases
      diagnosed with VTE, DVT and PE for a period between March 2004 and June 2009 were
      identified through the hospital-based database system. The 2006 New Zealand
      Census data were used to calculate the rate of diagnosis. RESULTS: The observed
      annual incidence of VTE during this period was 81.6 per 100000 population. The
      relative risks of VTE when comparing European subjects with Maori, Pacific Island
      and Asian subjects after age standardization were 1.98 (95% confidence interval
      [CI], 1.63-2.41), 3.22 (95% CI, 2.60-3.99) and 4.02 (95% CI, 3.34-4.84),
      respectively. Relative risks of DVT after age standardization when comparing
      European subjects with Maori, Pacific Island and Asian subjects, were 2.14 (95%
      CI, 1.72-2.66), 3.20 (95% CI, 2.46-4.17) and 4.75 (95% CI, 3.80-5.94),
      respectively. Indirect age standardization was used for comparison of the
      diagnosis of PE. The ratio between the calculated expected number of cases and
      the actual number of cases was 1.32 (95% CI, 0.89-1.75) for Maori subjects, 2.96
      (95% CI, 1.89-4.03) for Pacific Islanders and 3.89 (95% CI, 3.00-4.78) for
      Asians. CONCLUSION: Europeans have a significantly higher incidence of VTE
      compared with Maori, Pacific Island and Asian populations.

PMID- 24283770
TI  - The 2013 Nobel Prize in Physiology or Medicine.

PMID- 24283771
TI  - Third-party tolerogenic dendritic cells reduce allo-reactivity in vitro and
      ameliorate the severity of acute graft-versus-host disease in allo-bone marrow
      transplantation.
AB  - Tolerogenic dendritic cells (tDCs) potently induce and maintain tolerance based
      on their distinct characteristics compared with conventional DCs. Recent reports
      show that donor or host tDCs promote allograft survival in mice. In this study,
      the efficacy of third-party tDCs in the prevention of acute graft-versus-host
      disease (aGVHD) was evaluated. In vitro, tDCs derived from the bone marrow (BM)
      of D1 mice were induced by GM-CSF, IL-10 and TGF-beta1. The phenotypes,
      expression of cytokines and suppression of tDCs were analysed. In vivo, the
      effects of adoptive transfer of third-party-tDCs were evaluated in an MHC
      mismatched aGVHD mouse model. Survival, body weight, GVHD scoring,
      histopathological specimens and serum cytokines were analysed in tDC-treated mice
      and untreated controls. Tolerogenic DCs had low expression of MHC and co
      stimulatory molecules, expressed high levels of 'immunosuppressive' cytokines and
      suppressed allo-CD4(+) T cell proliferation. In the B6->D2 mouse model, all aGVHD
      mice died within 18 days. Fortunately, third-party tDCs transferred at low doses
      (10(4)) effectively prolonged survival after allo-BMT. Furthermore, in the mice
      treated with 10(4) tDCs, serum levels of IL-10/TGF-beta were significantly higher
      and the percentage of Foxp3(+) cells continually increased compared with the mice
      treated with other doses of tDCs. Third-party tDCs play a crucial role in
      reducing the severity of aGVHD by modulating the secretion of various cytokines
      and expanding Foxp3(+) regulatory T cells, which suggests the possibility of
      using third-party tDCs for therapeutic applications. Furthermore, special
      attention should be paid to the optimal range of tDCs for preventing allograft
      rejection.

PMID- 24283772
TI  - Immunogenicity and protective efficacy conferred by a novel recombinant
      Mycobacterium bovis bacillus Calmette-Guerin strain expressing interleukin-12p70
      of human cytokine and Ag85A of Mycobacterium tuberculosis fusion protein.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) immunization provides
      protection against tuberculosis (TB) in infants, but the antituberculosis
      protective immunity wanes gradually after initial immunization and lasts less
      than 15 years. Therefore, more efficacious vaccines are urgently needed. In this
      study, we constructed a new tuberculosis vaccine of recombinant BCG strain (rBCG
      IA), which could express IL-12p70 of human cytokine and Ag85A of M. tuberculosis
      fusion protein, and investigated its immunogenicity in BALB/c mice by measuring
      antibody titres, proliferation rate of splenocytes, ratios of CD4(+) T and CD8(+)
      T cells stimulated by specific antigens and levels of IFN-gamma production in
      antigen-stimulated splenocyte cultures. Meanwhile, we evaluated its protective
      efficacy against M. tuberculosis H37Rv infection through detecting lung
      histopathology, organ bacterial loads and lung acid-fast stain. Immunogenicity
      experiments illustrated that from 2nd to 8th week after immunization, the rBCG-IA
      vaccine was able to induce the highest level of antibody titres, proliferation
      rate of splenocytes and IFN-gamma production among groups and gained improved
      ratio of CD4(+) T and CD8(+) T cells from 6th to 8th week after vaccination. And
      from 2nd to 8th week after M. tuberculosis H37Rv infection, the score of
      pathology and bacterial loads in the rBCG-IA group were obviously lower than that
      in rBCG-I group, rBCG-A group or control group (PBST group), but similar to that
      in BCG group. This study suggested that rBCG-IA was able to elicit stronger
      humoral and cellular immune responses, but could only confer similar protective
      efficacy compared with its parental BCG vaccine.

PMID- 24283773
TI  - Association of disease severity with IL-1 levels in methotrexate-treated
      psoriasis patients.
AB  - Interleukin-1 plays a key role in inflammation and keratinocyte activation. It is
      an important mediator in the initiation and maintenance of psoriatic plaques and
      may represent an attractive therapeutic target. The aim of this study is to
      evaluate the effect of Methotrexate (MTX) on IL-1 alpha and IL-1 beta levels in
      both plasma and skin biopsy of patients with psoriasis and to investigate their
      association with clinical disease activity. Forty-five control subjects and 58
      patients with psoriasis were recruited for this study. The patients were treated
      with 7.5 mg of MTX per week for 12 weeks. Folic acid was given at 5 mg once daily
      except on the day of MTX for 12 weeks. Blood samples and lesional skin biopsy
      were taken. Disease severity was assessed by Psoriasis Area Severity Index (PASI)
      score. IL-1 levels in plasma and skin biopsy were analysed using ELISA. PASI
      score declined significantly (P < 0.001) from day 0 to 12 weeks of MTX treatment.
      IL-1 alpha level in plasma and skin biopsy was reduced at day 0 sample and
      elevated significantly (P < 0.001) after MTX treatment. IL-1beta level in plasma
      and skin biopsy was higher at day 0 sample and reduced significantly (P < 0.001)
      after MTX treatment. IL-1alpha levels and PASI score showed inverse correlation
      score before and after treatment with MTX. Whereas IL-1beta levels showed
      positive correlation before and after treatment with MTX. Decreasing IL-1beta
      levels by MTXs in psoriasis may block the Th17 differentiation. This shows the
      therapeutic effect of MTX in controlling the immunopathogenesis of psoriasis.

PMID- 24283774
TI  - Adaptive responses of calcium and phosphate homeostasis in goats to low nitrogen
      intake: renal aspects.
AB  - In a previous study, in goats, we showed that apart from variations in dietary
      calcium (Ca) and phosphorus intake, also low dietary nitrogen (N) intake altered
      plasma concentrations of hormones, which regulate Ca and phosphate (Pi )
      homeostasis. These hormonal responses in goats were in accordance with findings
      in monogastric animals and humans with low protein intake. In the aforementioned
      studies, alterations of electrolyte transport in the kidneys were also observed.
      However, whether renal electrolyte transport in goats is also involved in the
      adaptation of Ca and Pi homeostasis to low N intake remains unknown. Thus, the
      aim of the present study was to investigate whether in addition to the hormonal
      changes, as observed in our former study, renal Ca transport and renal Pi
      transport were also altered by low N intake in goats. Therefore, in kidney
      samples from the goats used in our former study, the protein expression of Ca and
      Pi transporters and of related regulatory proteins was examined. Furthermore, the
      uptake of Pi into isolated brush border membrane vesicles (BBMV) was detected.
      The results showed that the protein amount of the renal sodium-dependent Pi
      transporter NaPi IIa was elevated, and concomitantly, protein expression of its
      upstream regulators, the parathyroid hormone receptor and the extracellular
      signal-regulated kinases 1 and 2 was decreased. However, Pi uptake into renal
      BBMV was not enhanced. Furthermore, protein expression of the renal Ca channel,
      the transient receptor potential cation channel subfamily V member 5 (TRPV5) and
      of the vitamin D receptor was not influenced by dietary N reduction. We conclude
      that regulation of renal Pi transporter expression in goats is involved in the
      adaptation of electrolyte homeostasis to low N intake. 

PMID- 24283775
TI  - Mass transport at infinite regular arrays of microband electrodes submitted to
      natural convection: theory and experiments.
AB  - Mass transport at infinite regular arrays of microband electrodes was
      investigated theoretically and experimentally in unstirred solutions. Even in the
      absence of forced hydrodynamics, natural convection limits the convection-free
      domain up to which diffusion layers may expand. Hence, several regimes of mass
      transport may take place according to the electrode size, gap between electrodes,
      time scale of the experiment, and amplitude of natural convection. They were
      identified through simulation by establishing zone diagrams that allowed all
      relative contributions to mass transport to be delineated. Dynamic and steady
      state regimes were compared to those achieved at single microband electrodes.
      These results were validated experimentally by monitoring the chronoamperometric
      responses of arrays with different ratios of electrode width to gap distance and
      by mapping steady-state concentration profiles above their surface through
      scanning electrochemical microscopy. 

PMID- 24283777
TI  - Psychometric properties of the Cambridge depersonalization scale in Puerto Rico.
AB  - Depersonalization experiences have been studied in the United States and Europe,
      but there is a dearth of investigations with Latino populations. In the current
      study we examined the psychometric properties of the Spanish version of the
      Cambridge Depersonalization Scale (CDS) in 300 adult individuals from the
      community and compared the results with those reported previously with non-Latino
      clinical populations. Discrepant findings have been reported with respect to the
      factor structure of the CDS. We performed exploratory and confirmatory factor
      analyses on the CDS items and compared our results with published analyses on
      other populations. Results revealed that the psychometric properties of the CDS,
      such as reliability, seem adequate, although the factor structure of the CDS
      seems to be inconsistent across studies. We selected a 4-factor solution that was
      most parsimonious and best fit our data. Furthermore, we obtained a moderate,
      statistically significant relationship (r = .64, p = .001) between the CDS and
      the Dissociative Experiences Scale. Our results, utilizing a nonclinical sample
      of Puerto Rican adults, suggest that depersonalization experiences can be
      reliably measured in a Latino and Spanish-speaking population. 

PMID- 24283776
TI  - Impact of intracellular domain flexibility upon properties of activated human 5
      HT3 receptors.
AB  - BACKGROUND AND PURPOSE: It has been proposed that arginine residues lining the
      intracellular portals of the homomeric 5-HT3 A receptor cause electrostatic
      repulsion of cation flow, accounting for a single-channel conductance
      substantially lower than that of the 5-HT3 AB heteromer. However, comparison of
      receptor homology models for wild-type pentamers suggests that salt bridges in
      the intracellular domain of the homomer may impart structural rigidity, and we
      hypothesized that this rigidity could account for the low conductance.
      EXPERIMENTAL APPROACH: Mutations were introduced into the portal region of the
      human 5-HT3 A homopentamer, such that putative salt bridges were broken by
      neutralizing anionic partners. Single-channel and whole cell currents were
      measured in transfected tsA201 cells and in Xenopus oocytes respectively.
      Computational simulations of protein flexibility facilitated comparison of wild
      type and mutant receptors. KEY RESULTS: Single-channel conductance was increased
      substantially, often to wild-type heteromeric receptor values, in most 5-HT3 A
      mutants. Conversely, introduction of arginine residues to the portal region of
      the heteromer, conjecturally creating salt bridges, decreased conductance. Gating
      kinetics varied significantly between different mutant receptors. EC50 values for
      whole-cell responses to 5-HT remained largely unchanged, but Hill coefficients
      for responses to 5-HT were usually significantly smaller in mutants.
      Computational simulations suggested increased flexibility throughout the protein
      structure as a consequence of mutations in the intracellular domain. CONCLUSIONS
      AND IMPLICATIONS: These data support a role for intracellular salt bridges in
      maintaining the quaternary structure of the 5-HT3 receptor and suggest a role for
      the intracellular domain in allosteric modulation of cooperativity and agonist
      efficacy.

PMID- 24283778
TI  - Combined long-acting bronchodilator single therapy for COPD.
AB  - INTRODUCTION: In COPD, the long-acting bronchodilators are not always able to
      provide an appropriate bronchodilator effect in terms of amplitude and duration
      and this can result in increased severity of respiratory symptoms and in
      worsening of health status. Combined long-acting bronchodilators can address this
      limitation. AREAS COVERED: Analysis of a recent study evaluating the efficacy and
      safety of 26 weeks of therapy with glycopyrronium+indacaterol single inhaler
      (QVA149) versus each component, versus tiotropium and versus placebo. EXPERT
      OPINION: Such a combination can provide a superior and sustained bronchodilator
      effect and can minimize the respiratory symptoms resulting from a suboptimally
      inhibited bronchoconstriction.

PMID- 24283779
TI  - Decision analysis in the clinical neurosciences: a systematic review of the
      literature.
AB  - Clinical decision analysis can be a useful scientific tool for individual patient
      management, for planning of clinical research and for reaching consensus about
      clinical problems. We systematically reviewed the decision analytic studies in
      the clinical neurosciences that were published between 1975 and July 1994. All
      studies were assessed on aspects of clinical applicability: presence of case and
      context description, completeness of the analysed strategies from a clinical
      point of view, extendibility of the analyses to different patient profiles, and
      up-to-date-ness. Fifty-nine decision analyses of twenty-eight different clinical
      problems were identified. Twenty-eight analyses were based on the theory of
      subjective expected utility, twelve on cost-effectiveness analysis. Four studies
      used ROC analysis, and fifteen were risk-, or risk-benefit analyses. At least six
      studies could have been improved by more elaborately disclosing the context of
      the clinical problem that was addressed. In eleven studies, the effect of
      different, yet plausible assumptions was not explored, and in eighteen studies
      the reader was not informed how to extend the results of the analysis to patients
      with (slightly) different clinical characterisitics. All studies had, by nature,
      the potential to promote insight into the clinical problem and focus the
      discussion on clinically important aspects, and gave clinically useful advice. We
      conclude that clinical decision analysis, as an explicit, quantitative approach
      to uncertainty in decision making in the clinical neurosciences will fulfill a
      growing need in the near future. 

PMID- 24283780
TI  - The prevalence and clinical correlates of apathy and irritability in Alzheimer's
      disease.
AB  - We examined the prevalence and correlates of apathy and irritability in a
      consecutive series of 101 patients with probable Alzheimer's disease (AD). Based
      on clinical criteria, 46 (46%) patients had apathy, and 13 (13%) patients had
      irritability. Apathy was significantly associated with more severe impairments in
      activities of daily living, significantly more severe extrapyramidal signs, and a
      significantly higher frequency of both major depression and dysthymia. Patients
      with irritability had significantly more severe impairments in activities of
      daily living and significantly higher depression and anosognosia scores. On the
      other hand, neither apathy nor irritability were significantly associated with
      deficits in specific cognitive domains. 

PMID- 24283781
TI  - MRI in corticobasal degeneration.
AB  - Corticobasal degeneration is a degenerative disease characterized by asymmetric
      brain atrophy and clinically by asymmetric onset of an akinetic-rigid syndrome
      with apraxia, dysarthria and dysphagia. Diagnosis must be confirmed by autopsy.
      We have investigated the ability of MRI to detect asymmetric atrophy to support
      the clinical diagnosis and permit differential diagnosis against other
      degenerative disorders. Ten patients with clinical suspicion of corticobasal
      degeneration were studied by brain MRI, and the images were reviewed with the
      side of greater clinical involvement unknown to the reviewer. The original
      reports of MR scans were also reviewed. MRI demonstrates that cortical atrophy is
      asymmetric and more marked in the posterior frontal and mainly in the parietal
      regions on the side contralateral to the clinical symptoms. Asymmetry was rarely
      detected on the first reading. Our review of MRI findings demonstrates that it is
      possible to detect asymmetrical parietal atrophy, thus supporting the clinical
      diagnosis of corticobasal degeneration. It is essential to be aware of the
      disease and alert for asymmetries in order to discern the more involved side. No
      abnormalities were detected in the basal ganglia. 

PMID- 24283782
TI  - Movement disorders in ischemic stroke: clinical study of 22 patients.
AB  - Movement disorders (bemichorea-hemiballismus, hemidystonia and isolated tremor)
      are an uncommon clinical manifestation in ischemic stroke (IS), and their
      anatomical basis is poorly understood. We analyzed the clinical and neuroimaging
      characteristics of 22 consecutive patients who bad movement disorders associated
      with cerebral infarction (MDCI), studied at four institutions over 8 years. In
      one institution (from the La Alianza-Central Hospital of Barcelona Stroke
      Registry) nine patients with MDCI were identified among 1099 consecutive first
      ever stroke patients (0.8%) (908 with IS, 1%). Fifteen out of 22 patients (68%)
      had hemichorea-hemiballismus, five (23%) hemidystonia and two (9%) isolated
      tremor. MDCI were more often left sided (n = 15, 68%), being bilateral in one
      patient (4.5%). A lesion was found on neuroimaging (CT and/or MRI) in 15 patients
      (68%), in the territory of the posterior cerebral artery (n = 8) and middle
      cerebral artery (six deep and one superficial). The most commonly involved
      structure was the thalamus (n = 8, 36.5%). IS subtypes were; presumed lacunar
      infarcts in 14 patients (64%), atherothrombotic infarcts in two patients (9%),
      cardioembolic infarcts in two patients (9%) and infarcts of unknown etiology in
      four patients (18%). Hemichorea-hemiballismus was the most common type of MDCI in
      our study, usually being the result of a thalamic infarction. The thalamus was
      the most frequently damaged structure underlying all types of MDCI. There was a
      striking propensity of MDCI which resulted from nondominant deep hemispheric
      small vessel infarctions. 

PMID- 24283783
TI  - Prognostic value of electrodiagnosis in the Dutch Guillain-Barre study.
AB  - In the Dutch Guillain-Barre trial, three EMGs were performed according to a rigid
      protocol at early stages of the disease in 147 Guillain-Barre patients who were
      unable to walk independently. Independent locomotion 8 weeks and 6 months after
      entry were considered to be the outcome measures of most clinical value.
      Electrodiagnostic data obtained 1 week after entry were concluded to be most
      important for studying prognostic value. This has been attributed to the fact
      that 87% of the patients were in the nadir of their disease at that moment In
      univariate analysis, CMAP amplitudes of thenar and hypothenar muscles obtained
      after distal and proximal stimulation, as well as the recruitment pattern on
      maximal voluntary effort in these tested muscles, were significant predictors for
      outcome 8 weeks and 6 months after entry to the study. Motor nerve conduction
      velocity and distal motor latencies of ulnar and median nerves were weak
      predictors for outcome at 8 weeks after entry. In multivariate analysis the
      hypothenar CMAP amplitude on distal stimulation and recruitment pattern of
      abductor digiti minimi muscle both had an independent predictive value for
      independent locomotion 8 weeks after entry. 

PMID- 24283784
TI  - Transcranial Doppler monitoring of cerebral embolism in atrial fibrillation and
      prosthetic valves. Clinical correlations.
AB  - Transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) permits
      the detection of high intensity transient signals (HITS), which are believed to
      represent microemboli. Non-valvular atrial fibrillation (NVAF) and prosthetic
      heart valves (PV) are important risk factors for embolic stroke. We evaluated
      both the prevalence and the frequency of microemboli in these high risk groups
      and the correlation with previous stroke. Sixty-six patients were monitored for
      30 min on both MCAs sequentially. Twenty healthy subjects were studied as well.
      The total number of HITS recorded on both sides, expressed as HITS/h, was used
      for comparison. In NVAF patients (n = 24) the prevalence of HITS was 25%, in PV
      (n = 16) 62% and in those patients in whom PV coexisted with atrial fibrillation
      (PVAF) (n = 26), it was 42%. None in the control group showed HITS. HITS occurred
      significantly more frequently in PVAF (12.3/h) than in both NVAF (1.4/h, p =
      0.007) and PV (2.7/h, p = 0.011), whereas there was no difference between PV and
      NVAF. The prevalence of HITS was not statistically different in patients with and
      without previous stroke, but among HITS positive patients those with previous
      stroke had a significantly higher HITS frequency (18.9 vs 8.5/h, p = 0.04). In
      conclusion, in patients with cardiac embolic sources the frequency of HITS
      increases from the classes with the lower (NVAF, PV) to the class with the
      highest (PVAF) risk factor. Patients with previous stroke have more HITS than
      asymptomatic ones. Therefore, embolus detection monitoring seems a promising tool
      in the assessment of the individual stroke risk in patients with cardiac embolic
      sources. 

PMID- 24283785
TI  - Cerebrospinal fluid-filtration reduces TNF alpha in bacterial meningitis-CSF.
AB  - A 37 year old male was admitted with the diagnosis of bacterial meningitis.
      Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical
      condition did not suggest severely raised intracranial pressure, there were no
      localizing signs and symptoms. CSF was turpid, with 20.100/3/mm(3) , mainly
      polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased
      with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF
      filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall
      filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm(3) , TNF
      alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient
      could be discharged without sequelae. CSF filtration may be a highly effective
      method to reduce from the CSF pathogenetically important cytokines, such as TNF
      alpha, being responsible for intrathecal/meningeal inflammatory processes and
      triggered by cell-wall components of bacteria, e.g. pneumococci. 

PMID- 24283786
TI  - Intrafamilial heterogeneous clinical presentation of the mitochondrial 3243 MELAS
      mutation; molecular investigations among four generations.
AB  - We have identified the A3243G heteroplasmic point mutation in mitochondrial DNA
      from a female patient with headache as the main clinical feature. The
      mitochondrial origin of her disease was only suspected because of her brother
      with MELAS syndrome. Morphological and biochemical studies failed to reveal
      mitochondrial respiratory chain dysfunction in her muscle which contained 65% of
      mutated mitochondrial DNA molecules. Molecular studies performed among four
      generations (in the blood of seven subjects) showed the variable transmission of
      mutated molecules and pointed out the difficulty in giving genetic counsel. 

PMID- 24283787
TI  - The HhaI polymorphism in the CYP2D6 gene is not associated with Parkinson's
      disease in a Caucasian population.
AB  - Polymorphisms of the CYP2D6 gene have been reported in association with
      susceptibility to Parkinson's disease (PD). In a Japanese population, a HhaI
      polymorphism in the CYP2D6 gene was associated with a 5.56-fold risk of PD
      (Tsuneoka et al., 1993). We investigated the frequency of this polymorphism in
      Caucasian patients with sporadic PD and in healthy controls. Although the
      frequency of the polymorphism was significantly higher in Caucasians compared
      with Japanese, there was no association with PD. 

PMID- 24283788
TI  - A case of deaf-mutism as an expression of pure word deafness: neuroimaging and
      electrophysiological data.
AB  - We report a case of pure word deafness, clinically expressed as deaf-mutism in a
      17-year-old girl, who was affected from encephalitis when she was 18 months old
      and hadn't acquired language skills. Actually, physical examination revealed
      buccolingual apraxia and absence of spontaneous speech, auditory comprehension,
      repetition and denomination, whereas perception of non-verbal sounds was
      preserved. The seven waves of brainstem auditory evoked responses (BAER) were
      present with normal latencies; middle latency responses (MLR) were also normal.
      Magnetic resonance imaging (MRI) showed bilateral temporoparietal lesions. This
      case proves that lesions which may give rise to word deafness, when they occur in
      prelingual age, can determine a peculiar deafmutism clinical picture. 

PMID- 24283789
TI  - Regional cerebral blood flow patterns in migraine: what is the contribution to
      insight into disease mechanisms?

PMID- 24283790
TI  - Reply to Letter by V.K. Gupta-rCBF and migraine.

PMID- 24283791
TI  - A research agenda for acute care services delivery in low- and middle-income
      countries.
AB  - Delivery of acute care services at every level of the health system is essential
      to ensure appropriate evaluation and management of emergent illness and injury in
      low- and middle-income countries (LMICs). The health services breakout group at
      the 2013 Academic Emergency Medicine consensus conference developed
      recommendations for a research agenda along the following themes: infrastructure,
      implementation, and sustainable provision of acute care services. Based on these
      recommendations, a set of priorities was created to promote and guide future
      research on acute care services. 

PMID- 24283792
TI  - Right ventricular function and thrombus load in patients with pulmonary embolism
      and diagnostic delay.
AB  - INTRODUCTION: It has been reported that the time between symptom onset and
      objective diagnosis of pulmonary embolism (PE) does not affect patients'
      prognosis with regard to re-thrombosis and mortality risk. However, this
      observation is contra-intuitive and poorly understood. We further elaborated on
      this paradox by evaluating thrombus load and right ventricular function in
      patients with and without diagnostic delay. MATERIALS AND METHODS: We performed a
      post hoc analysis of a previously published observational prospective outcome
      study in 113 consecutive PE patients. Qanadli-score and RV/LV ratio were scored
      in all patients, as was the duration from symptom onset to clinical presentation
      and diagnosis. Diagnostic delay was defined as a period of more than 7 days
      between symptom onset and clinical presentation. Further endpoints were mortality
      and hospital readmission in a 6-week follow-up period. RESULTS: Twenty patients
      with and 93 patients without delay were studied, who had comparable baseline
      characteristics and co-morbidities. In linear analyses, Qanadli-score (R2 of
      0.021; P = 0.130) and RV/LV ratio (R2 < 0.001; P = 0.991) were not associated
      with diagnostic delay. Likewise, longer delay was not predictive of 6-week
      mortality (odds ratio, 0.65; 95% CI, 0.08-5.57) or hospital readmission (odds
      ratio, 0.75; 95% CI, 0.15-3.65). CONCLUSION: In our patient cohort, diagnostic
      delay was not associated with higher thrombus load or right ventricular
      dysfunction. This provides a possible explanation for the lack of prognostic
      relevance of diagnostic delay.

PMID- 24283793
TI  - Cultivating creativity in conservation science.
AB  - Conservation practitioners and scientists are often faced with seemingly
      intractable problems in which traditional approaches fail. While other sectors
      (e.g., business) frequently emphasize creative thinking to overcome complex
      challenges, creativity is rarely identified as an essential skill for
      conservationists. Yet more creative approaches are urgently needed in the effort
      to sustain Earth's biodiversity. We identified 4 strategies to develop skills in
      creative thinking and discuss underlying research and examples supporting each
      strategy. First, by breaking down barriers between disciplines and surrounding
      oneself with unfamiliar people, concepts, and perspectives, one can expand base
      knowledge and experiences and increase the potential for new combinations of
      ideas. Second, by meeting people where they are (both literally and
      figuratively), one exposes oneself to new environments and perspectives, which
      again broadens experiences and increases ability to communicate effectively with
      stakeholders. Third, by embracing risk responsibly, one is more likely to develop
      new, nontraditional solutions and be open to high-impact outcomes. Finally, by
      following a cycle of learning, struggle, and reflection, one can trigger
      neurophysiological changes that allow the brain to become more creative.
      Creativity is a learned trait, rather than an innate skill. It can be actively
      developed at both the individual and institutional levels, and learning to
      navigate the relevant social and practical barriers is key to the process. To
      maximize the success of conservation in the face of escalating challenges, one
      must take advantage of what has been learned from other disciplines and foster
      creativity as both a professional skill and an essential component of career
      training and individual development.

PMID- 24283795
TI  - Pseudo-rephasing and pseudo-free-induction-decay mechanism in two-color three
      pulse photon echo of a binary system.
AB  - We investigate the two-color three-pulse photon echo peak shift in a (left-right)
      binary system, where each component consists of a heterodimer. On the basis of
      the model, we find that the effect of the excitonic asymmetry between two
      components leads to an additional factor in the peak shift. A pseudo-rephasing
      and pseudo-free-induction-decay mechanism is proposed to explain the resultant
      negative peak shift, when the differences between the two left/right components
      have the opposite sign. In such a case, estimates of the electronic coupling
      strength via two- and one-color peak shift experiments lead to an underestimate
      of the coupling magnitude. 

PMID- 24283794
TI  - A novel approach for protein subcellular location prediction using amino acid
      exposure.
AB  - BACKGROUND: Proteins perform their functions in associated cellular locations.
      Therefore, the study of protein function can be facilitated by predictions of
      protein location. Protein location can be predicted either from the sequence of a
      protein alone by identification of targeting peptide sequences and motifs, or by
      homology to proteins of known location. A third approach, which is complementary,
      exploits the differences in amino acid composition of proteins associated to
      different cellular locations, and can be useful if motif and homology information
      are missing. Here we expand this approach taking into account amino acid
      composition at different levels of amino acid exposure. RESULTS: Our method has
      two stages. For stage one, we trained multiple Support Vector Machines (SVMs) to
      score eukaryotic protein sequences for membership to each of three categories:
      nuclear, cytoplasmic and extracellular, plus extra category nucleocytoplasmic,
      accounting for the fact that a large number of proteins shuttles between those
      two locations. In stage two we use an artificial neural network (ANN) to propose
      a category from the scores given to the four locations in stage one. The method
      reaches an accuracy of 68% when using as input 3D-derived values of amino acid
      exposure. Calibration of the method using predicted values of amino acid exposure
      allows classifying proteins without 3D-information with an accuracy of 62% and
      discerning proteins in different locations even if they shared high levels of
      identity. CONCLUSIONS: In this study we explored the relationship between residue
      exposure and protein subcellular location. We developed a new algorithm for
      subcellular location prediction that uses residue exposure signatures. Our
      algorithm uses a novel approach to address the multiclass classification problem.
      The algorithm is implemented as web server 'NYCE' and can be accessed at
      http://cbdm.mdc-berlin.de/~amer/nyce.

PMID- 24283796
TI  - Clinical and tree hollow populations of human pathogenic yeast in Hamilton,
      Ontario, Canada are different.
AB  - Yeast are among the most frequent pathogens in humans. The dominant yeast causing
      human infections belong to the genus Candida and Candida albicans is the most
      frequently isolated species. However, several non-C. albicans species are
      becoming increasingly common in patients worldwide. The relationships between
      yeast in humans and the natural environments remain poorly understood.
      Furthermore, it is often difficult to identify or exclude the origins of disease
      causing yeast from specific environmental reservoirs. In this study, we compared
      the yeast isolates from tree hollows and from clinics in Hamilton, Ontario,
      Canada. Our surveys and analyses showed significant differences in yeast species
      composition, in their temporal dynamics, and in yeast genotypes between isolates
      from tree hollows and hospitals. Our results are inconsistent with the hypothesis
      that yeast from trees constitute a significant source of pathogenic yeast in
      humans in this region. Similarly, the yeast in humans and clinics do not appear
      to contribute to yeast in tree hollows. 

PMID- 24283797
TI  - Antibody radiolabeling techniques to optimize cellular retention.
AB  - Radiolabeling of antibodies and antibody fragments facilitates the development of
      new targeted therapeutics or tracking and validation of biosimilars. The typical
      metal ion chelators that can be used for radiolabeling reactions have
      residualizing properties in tissues/tumors. A team at Genentech has developed an
      elegant new technique for combining iodine radiolabeling with an azamacrocyclic
      chelator to confer residualizing properties on the radioiodine metabolites.
      Robust protocols, such as this example, are required for the future development
      of protein based drugs. 

PMID- 24283798
TI  - Simultaneous determination of post-translational racemization and isomerization
      of N-terminal amyloid-beta in Alzheimer's brain tissues by covalent chiral
      derivatized ultraperformance liquid chromatography tandem mass spectrometry.
AB  - Typical markers of protein aging are spontaneous post-translational modifications
      such as amino acid racemization (AAR) and amino acid isomerization (AAI) during
      the degradation of peptides. The post-translational AAR and AAI could
      significantly induce the density and localization of plaque deposition in brain
      tissues. Alzheimer's disease (AD) is reliably related to the formation and
      aggregation of amyloid-beta peptide (Abeta) plaques in the human brain. No
      current analytical methods can simultaneously determine AAR and AAI during the
      degradation of Abeta from AD patients. We now report a covalent chiral
      derivatized ultraperformance liquid chromatography tandem mass spectrometry (CCD
      UPLC-MS/MS) method for the determination of post-translational AAR and AAI of N
      terminal Abeta (N-Abeta1-5) in human brain tissues. When subjected to tryptic N
      Abeta1-5 from post-translationally modified natural Abeta in focal brain tissues
      by the CCD procedure, it was monitored at m/z 989.6->637.0/678.9 during
      electrospray collision-induced dissociation. These N-Abeta1-5 fragments with l
      aspartic acid (l-Asp), d-Asp, l-isoAsp, and d-isoAsp could be separated using the
      UPLC system with a conventional reversed-phase column and mobile phase. The
      quantification of these peptides was determined using a stable isotope [(15)N]
      labeled Abeta1-40 internal standard. The CCD-UPLC-MS/MS assay of potential N
      Abeta1-5 allowed for the discovery of the present and ratio levels of these N
      Abeta1-5 sequences with l-Asp, d-Asp, l-isoAsp, and d-isoAsp. 

PMID- 24283799
TI  - Mechanisms counteracting the growth of large grains in industrial ZnS grown by
      chemical vapor deposition.
AB  - Polycrystalline ZnS produced by chemical vapor deposition (CVD) is analyzed using
      X-ray diffraction (XRD) and scanning electron microscopy (SEM) including electron
      backscatter diffraction (EBSD) to gain insight into the growth mechanism.
      Epitaxial growth of ZnS (111) layers is indicated in cubic CVD-ZnS. Mechanisms
      counteracting the growth of large, homogeneously oriented grains are proposed.
      This includes the summation of faults at low-angle grain boundaries during the
      deposition of new layers as well as the formation of new growth directions
      perpendicular to the sides of large grains. Wurtzite could be identified as a
      product of instable deposition conditions at the beginning and end of the
      deposition process. 

PMID- 24283800
TI  - A systematic review of instruments for assessment of capacity in activities of
      daily living in children with developmental co-ordination disorder.
AB  - Children with developmental co-ordination disorder (DCD) face evident motor
      difficulties in activities of daily living (ADL). Assessment of their capacity in
      ADL is essential for diagnosis and intervention, in order to limit the daily
      consequences of the disorder. The aim of this study is to systematically review
      potential instruments for standardized and objective assessment of children's
      capacity in ADL, suited for children with DCD. As a first step, databases of
      MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies that
      described instruments with potential for assessment of capacity in ADL. Second,
      instruments were included for review when two independent reviewers agreed that
      the instruments (1) are standardized and objective; (2) assess at activity level
      and comprise items that reflect ADL; and (3) are applicable to school-aged
      children that can move independently. Out of 1507 publications, 66 publications
      were selected, describing 39 instruments. Seven of these instruments were found
      to fulfil the criteria and were included for review: the Bruininks-Oseretsky Test
      of Motor Performance-2 (BOT2); the Do-Eat (Do-Eat); the Movement Assessment
      Battery for Children-2 (MABC2); the school-Assessment of Motor and Process Skills
      (schoolAMPS); the Tuffts Assessment of Motor Performance (TAMP); the Test of
      Gross Motor Development (TGMD); and the Functional Independence Measure for
      Children (WeeFIM). As a third step, for the included instruments, suitability for
      children with DCD was discussed based on the ADL comprised, ecological validity
      and other psychometric properties. We concluded that current instruments do not
      provide comprehensive and ecologically valid assessment of capacity in ADL as
      required for children with DCD. 

PMID- 24283801
TI  - Clinical and epidemiologic phenotypes of childhood asthma.
AB  - RATIONALE: Clinical and epidemiologic approaches have identified two distinct
      sets of classifications for asthma and wheeze phenotypes. OBJECTIVES: To compare
      epidemiologic phenotype definitions identified by latent class analysis (LCA)
      with clinical phenotypes based on patient histories, diagnostic work-up, and
      treatment responses. To relate phenotypes to genetic and environmental
      determinants as well as diagnostic and treatment-related parameters. METHODS: LCA
      was performed in an international multicenter birth cohort based on yearly
      questions about current wheeze until age 6 years. Associations of wheeze classes
      and clinical phenotypes with asthma-related characteristics such as atopy, lung
      function, fraction of exhaled nitric oxide, and medication use were calculated
      using regression models. MEASUREMENTS AND MAIN RESULTS: LCA identified five
      classes, which verified the clinically defined wheeze phenotypes with high
      sensitivity and specificity; the respective receiver operating characteristics
      curves displayed an area under the curve ranging from 84% (frequent wheeze) to
      85% (asthma diagnosis) and 87% (unremitting wheeze) to 97% (recurrent unremitting
      wheeze). Recurrent unremitting wheeze was the most specific and unremitting
      wheeze at least once the most sensitive definition. The latter identified a
      subgroup of children with decreased lung function, increased genetic risk, and in
      utero smoke exposure (ODDS RATIO, 2.03; 95% CONFIDENCE INTERVAL, 1.12-3.68; P =
      0.0191), but without established asthma diagnosis and treatment. CONCLUSIONS:
      Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA
      phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we
      identified children with clinically conspicuous but undiagnosed disease. Because
      of their high area under the curve values, clinical phenotypes such as
      (recurrent) unremitting wheeze emerged as promising alternative asthma
      definitions for epidemiologic studies.

PMID- 24283802
TI  - Sodium oxybate in the treatment of alcohol dependence: from the alcohol
      withdrawal syndrome to the alcohol relapse prevention.
AB  - INTRODUCTION: Sodium oxybate (SMO) has been shown to be safe and effective in the
      treatment of patients with alcohol use disorders (AUDs); it was approved in Italy
      and Austria for the treatment of alcohol withdrawal syndrome and for relapse
      prevention. The focus of this review is to discuss the clinical evidence on the
      therapeutic potential of SMO for AUDs. AREAS COVERED: This review covers the
      studies in patients with alcohol withdrawal syndrome who received SMO for the
      treatment of withdrawal symptoms and the studies in patients with AUDs who
      received SMO to achieve total alcohol abstinence, reduction of alcohol intake,
      and relapse prevention. Relevant medical literature on SMO was identified by
      searching databases including MEDLINE and EMBASE (searches last updated 20
      September 2013), bibliographies from published literature, clinical trial
      registries/databases, and websites. EXPERT OPINION: SMO has proved safe and
      effective in the treatment of alcohol withdrawal syndrome and in the prevention
      of relapses. Craving for and abuse of SMO have been reported, in particular in
      some subtypes of alcoholic patients, e.g., those affected by co-addiction and/or
      psychiatric comorbidity. Future multicenter, multinational, randomized clinical
      trials should be useful to optimize the treatments in relation with patients'
      characteristics, for example, pharmacogenetic, neurobiological, and
      psychological.

PMID- 24283804
TI  - Non-steroidal anti-inflammatory drug-activated gene-1 expression levels in nasal
      polyposis.
AB  - OBJECTIVES: This study aims to investigate the possible role of non-steroidal
      anti-inflammatory drug-activated gene-1 (NAG-1) in nasal polyp development.
      PATIENTS AND METHODS: Twenty-one patients (15 males, 6 females; mean age 44.3
      years; range 16 to 65 years) who underwent endoscopic sinus surgery for nasal
      polyposis (NP) were included in the study. Inferior turbinate mucosa samples were
      taken in addition to the polyp tissue which was already removed during routine
      procedure. The NAG-1 gene messenger ribonucleic acid (mRNA) expression levels of
      the polyp tissue and healthy turbinate mucosa were examined by real-time
      polymerase chain reaction (PCR). Patients were divided into two groups based on
      the presence or absence of comorbid asthma. RESULTS: The NAG-1 gene expression of
      the polyp tissue was 1,089 fold higher, compared to the healthy nasal mucosa
      (p=0.757). The NAG-1 mRNA levels were 2.13 times decreased in the patients with
      comorbid asthma (p=0.275). There was no statistically significant difference
      between the groups. CONCLUSION: With the findings of this study NAG-1 gene may
      play a role in nasal polyp development in the presence of comorbid asthma.

PMID- 24283803
TI  - Inhibition of protein kinase CK2 with the clinical-grade small ATP-competitive
      compound CX-4945 or by RNA interference unveils its role in acute myeloid
      leukemia cell survival, p53-dependent apoptosis and daunorubicin-induced
      cytotoxicity.
AB  - BACKGROUND: The involvement of protein kinase CK2 in sustaining cancer cell
      survival could have implications also in the resistance to conventional and
      unconventional therapies. Moreover, CK2 role in blood tumors is rapidly emerging
      and this kinase has been recognized as a potential therapeutic target. Phase I
      clinical trials with the oral small ATP-competitive CK2 inhibitor CX-4945 are
      currently ongoing in solid tumors and multiple myeloma. METHODS: We have analyzed
      the expression of CK2 in acute myeloid leukemia and its function in cell growth
      and in the response to the chemotherapeutic agent daunorubicin We employed acute
      myeloid leukemia cell lines and primary blasts from patients grouped according to
      the European LeukemiaNet risk classification. Cell survival, apoptosis and
      sensitivity to daunorubicin were assessed by different means. p53-dependent CK2
      inhibition-induced apoptosis was investigated in p53 wild-type and mutant cells.
      RESULTS: CK2a was found highly expressed in the majority of samples across the
      different acute myeloid leukemia prognostic subgroups as compared to normal CD34+
      hematopoietic and bone marrow cells. Inhibition of CK2 with CX-4945, K27 or
      siRNAs caused a p53-dependent acute myeloid leukemia cell apoptosis. CK2
      inhibition was associated with a synergistic increase of the cytotoxic effects of
      daunorubicin. Baseline and daunorubicin-induced STAT3 activation was hampered
      upon CK2 blockade. CONCLUSIONS: These results suggest that CK2 is over expressed
      across the different acute myeloid leukemia subsets and acts as an important
      regulator of acute myeloid leukemia cell survival. CK2 negative regulation of the
      protein levels of tumor suppressor p53 and activation of the STAT3 anti-apoptotic
      pathway might antagonize apoptosis and could be involved in acute myeloid
      leukemia cell resistance to daunorubicin.

PMID- 24283805
TI  - [An evaluation of histopathological changes in ethmoid sinus mucosa after
      endoscopic sinus surgery].
AB  - OBJECTIVES: This study aims to evaluate postoperative histopathological changes
      in ethmoid sinus mucosa in patients undergoing limited or extensive endoscopic
      sinus surgery (ESS) due to chronic rhinosinusitis. PATIENTS AND METHODS: A total
      of 120 patients (74 males, 46 females; mean age 33 years; range 18 to 56 years)
      with chronic rhinosinusitis who underwent limited ESS (n=40), extensive ESS
      (n=40) and septoplasty or septorhinoplasty (n=40) in our clinic between May 2009
      and October 2010 were enrolled. The control group consisted of patients who
      underwent septoplasty and septorhinoplasty alone. We took samples from the
      anterior ethmoid sinus mucosa at postoperative sixth months for the patients who
      underwent ESS and intraoperatively for the control patients. Tissue slices of
      mucosa samples were investigated under light microscope in terms of epithelial
      erosion, squamous metaplasia, submucosal fibrosis, basal membrane thickening,
      submucosal edema and submucosal inflammation. Histopathological findings of
      limited and extensive ESS groups were compared to each other and the control
      group. RESULTS: The incidence of squamous metaplasia and submucosal fibrosis was
      significantly higher in extensive ESS group, compared to limited ESS group
      (p=0.003 and p<0.001, respectively). Both of ESS groups had significantly higher
      incidences of epithelial erosion, submucosal fibrosis, basal membrane thickening,
      submucosal edema, submucosal inflammation, compared to the control group
      (p<0.001). CONCLUSION: Our study results show that ethmoid sinus mucosa may be
      still abnormal at the postoperative sixth month following ESS, regardless of the
      extension of ethmoidectomy. These patients should be followed closely, as they
      may have recurrent rhinosinusitis in the postoperative period due to impaired
      mucociliary activity.

PMID- 24283806
TI  - A comparison of histopathological results of conventional surgery and transoral
      radiofrequency ablation in early stage laryngeal carcinoma.
AB  - OBJECTIVES: This study aims to compare histopathological results of conventional
      surgery and transoral radiofrequency ablation in patients with early stage
      laryngeal carcinoma. PATIENTS AND METHODS: Between January 2006 and May 2010, 36
      patients (34 males, 2 females; mean age 61.6 years; range 43 to 77 years) who
      underwent partial laryngectomy in our clinic were retrospectively analyzed. All
      patients were randomized to partial laryngectomy with radiofrequency ablation or
      conventional surgery. Hoarseness due to early stage T1 and selected T2N0 vocal
      cord lesions was an indication for surgery. Of 20 patients receiving conventional
      surgery, 14 underwent partial laryngectomy, while six patients underwent
      cordectomy for the excision of tumors. Tumors were excised by transoral
      radiofrequency ablation in 16 patients. RESULTS: We observed thermal artifacts in
      four patients undergoing conventional surgery and in 13 patients undergoing
      transoral radiofrequency ablation. There was also hemorrhage in 16 patients
      undergoing conventional surgery and in seven patients undergoing transoral
      radiofrequency ablation. Histopathological examination revealed that the surgical
      margins were safe in 10 patients after radiofrequency ablation. The specimens
      obtained from six patients showed thermal artifacts which complicated
      histopathological examination. Sixteen (80%) of 20 conventional surgery patients
      and nine (56%) of 16 radiofrequency ablation patients had safe surgical margins.
      CONCLUSION: In radiofrequency ablation, the surgical zone must be larger than in
      conventional surgery due to the high risk of tissue damage and complicated
      histopathological examination.

PMID- 24283807
TI  - [Normative values of middle ear resonance frequency in normal hearing adults].
AB  - OBJECTIVES: This study aims to determine the normative values of middle ear
      resonance frequency in healthy adults. PATIENTS AND METHODS: Sixty adult
      volunteers (32 females, 28 males; mean age 31.8+/-7.1 years; range 21 to 46
      years) with normal otoscopic examination, audiometry and electroacoustic
      immitancemetry findings were enrolled in the study. The middle ear resonance
      frequencies were calculated by multifrequency tympanometry. RESULTS: The mean
      resonance frequency for all volunteers was 999.6+/-134.9 Hz. The mean resonance
      frequency was 1020.8+/-140.6 Hz for the right ear, and 978.3+/-180.5 Hz for the
      left ear. The mean resonance frequencies for the right- and left-side were
      1023.2+/-146.9 Hz and 912.5+/-177.8 Hz in males, and 1018.8+/-137.2 Hz and
      1035.9+/-164.7 Hz in females, respectively. There was no statistically
      significant difference in the mean resonance frequency of the right ears between
      the males and females (p=0.9), whereas the mean resonance frequency of the left
      ears was statistically significantly higher in females (p=0.007). CONCLUSION: The
      middle ear resonance frequency values may vary according to the side of the ear
      or gender.

PMID- 24283808
TI  - Surgical treatment of carotid body tumors.
AB  - OBJECTIVES: In this study, we report our clinical experience in a series of
      patients with carotid body tumors along with diagnosis, treatment and follow-up
      procedures in the light of related literature data. PATIENTS AND METHODS: Between
      November 2001 and May 2012, 10 patients (5 males, 5 females; mean age 53.2 years;
      range 27 to 80 years) who underwent surgery due to a carotid body tumor in our
      clinic were included. Diagnosis was based on ultrasonography, computed
      tomography, magnetic resonance imaging, magnetic resonance angiography, selective
      carotid angiography, balloon occlusion test, biochemical tests and preoperative
      embolization. Complications were also recorded. RESULTS: Balloon occlusion test
      was performed in all patients preoperatively, while embolization was implemented
      in seven patients. All masses were dissected by carotid artery subadventitial
      approach. Carotid integrity was maintained in nine patients, while a vein graft
      was used in one patient. Neurological disorder was observed in one patient,
      whereas transient hypoglossal paresis was in one patient who underwent saphenous
      vein grafting. CONCLUSION: Our study results suggest that (i) carotid body tumors
      should be handled with multidisciplinary approach; (ii) balloon occlusion test
      should be performed in all patients undergoing surgery; (iii) a particular
      attention should be paid to cranial and phrenic nerves, if it is necessary to
      extend the surgical field while removing the tumor; and (iv) pathological
      examination should be carried out by an experienced team and in a multi-centered
      fashion, if necessary.

PMID- 24283809
TI  - [Head and neck space infection presenting with Herpes Simplex virus].
AB  - A six-year-old girl was admitted to our clinic with the complaints of swelling,
      trismus, pain in the submandibular, submental and masticator area and vesicular
      lesions on the mandibular branch of trigeminal nerve (C5, V3). We present this
      case of head and neck space infection presenting with Herpes Simplex virus, as it
      is rarely seen. 

PMID- 24283810
TI  - A cutaneous angiosarcoma arising from the rhinophyma.
AB  - In this article, we report a 66-year-old male case of rhinophyma who had a
      persistent lesion on his nose for two-years. Despite steroid therapy, the lesion
      continued to grow. Histopathological and immunohistochemical findings were
      consistent with cutaneous angiosarcoma. Rhinophyma-like features should be
      considered as an unusual clinical manifestation of cutaneous angiosarcoma. 

PMID- 24283811
TI  - [A rare cause of oropharyngeal mass: bilateral aberrant internal carotid artery].
AB  - Bilateral pharyngeal internal carotid artery aberration is a rarely seen
      variation which poses a risk during the surgical interventions of this area. A 74
      year-old male patient was admitted to our clinic with the complaints of a
      sensation of fullness in his throat and dysphagia. Oropharyngeal examination
      revealed bilateral smooth-surfaced masses in the posterior pharyngeal wall.
      Magnetic resonance imaging showed an aberrant internal carotid artery. The
      patient was followed up with necessary warnings. The pulsation on the pharyngeal
      masses should be definitely evaluated and aberrant internal carotid artery should
      be kept in mind, if present. 

PMID- 24283812
TI  - An unusual foreign body in frontal sinus: silicone tube.
AB  - Foreign bodies in paranasal sinuses are very rare and more than half of them are
      encountered in maxillary sinus. Most of the foreign bodies are associated with
      maxillofacial trauma. Foreign body in the frontal sinus is even a rarer
      condition. Foreign bodies usually present with chronic symptoms and complications
      due to the delayed diagnosis. In this article, we report an unusual case of
      mucocele resulting from silicone nasolacrimal duct tube in right frontal sinus
      which was left or forgotten in nasal cavity after external dacryocystorhinostomy
      operation. The patient was treated surgically and her symptoms resolved after
      surgery. 

PMID- 24283813
TI  - Making recording and analysis of chief complaint a priority for global emergency
      care research in low-income countries.
AB  - The chief complaint is a patient's self-reported primary reason for presenting
      for medical care. The clinical utility and analytical importance of recording
      chief complaints have been widely accepted in highly developed emergency care
      systems, but this practice is far from universal in global emergency care,
      especially in limited-resource areas. It is precisely in these settings, however,
      that the use of chief complaints may have particular benefit. Chief complaints
      may be used to quantify, analyze, and plan for emergency care and provide
      valuable information on acute care needs where there are crucial data gaps.
      Globally, much work has been done to establish local practices around chief
      complaint collection and use, but no standards have been established and little
      work has been done to identify minimum effective sets of chief complaints that
      may be used in limited-resource settings. As part of the Academic Emergency
      Medicine consensus conference, "Global Health and Emergency Care: A Research
      Agenda," the breakout group on data management identified the lack of research on
      emergency chief complaints globally-especially in low-income countries where the
      highest proportion of the world's population resides-as a major gap in global
      emergency care research. This article reviews global research on emergency chief
      complaints in high-income countries with developed emergency care systems and
      sets forth an agenda for future research on chief complaints in limited-resource
      settings. 

PMID- 24283815
TI  - European Journal of Neurology: Four years on.

PMID- 24283816
TI  - The genetics of migraine.
AB  - Clinical, pathophysiological and genetic studies indicate that migraine without
      aura (MO) and migraine with aura (MA) are distinct entities. Compared with the
      general population, first degree relatives of probands with MO have a two-fold
      increased risk of MO. The mode of inheritance is most likely multifactorial
      inheritance without generational difference, but genetic heterogeneity can not be
      excluded. Compared with the general population, first degree relatives of
      probands with MA have a four-fold increased risk of MA. The mode of inheritance
      is most likely multifactorial inheritance without generational differences.
      Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of MA. A
      gene for FHM maps to chromosome 19. Some families with FHM do not link to this
      locus, indicating genetic heterogeneity of FHM. The gene for FHM is soon to be
      cloned. Loci for the more common types of migraine MO; and MA will problably be
      identified in the near future. 

PMID- 24283814
TI  - A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French
      Canadian population.
AB  - Familial focal epilepsy with variable foci (FFEVF) is a heterogeneous epilepsy
      syndrome originally described in the French-Canadian (FC) population. Mutations
      in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in
      a wide spectrum of other familial focal epilepsies. In this study, we aimed to
      determine the frequency of mutation of this gene in our large cohort of FC
      individuals with FFEVF, as well as familial and sporadic cases with focal
      epilepsy. We report a recurrent p.R843X protein-truncating mutation segregating
      in one large FFEVF and two small focal epilepsy FC families. Fine genotyping
      suggests an ancestral allele. A new p.T864M variant, predicted to be disease
      causing, was also identified in a small FC family. Overall, we identified DEPDC5
      mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our
      results support the view that mutations in the DEPDC5 gene are an important cause
      of autosomal dominant focal epilepsies in the FC population, including a founder
      mutation that is specific to this population. These findings may facilitate
      molecular diagnosis in clinical practice. 

PMID- 24283817
TI  - Changes in cerebral glucose metabolism with normal aging.
AB  - The pattern of changes in cerebral glucose metabolism occurring with normal aging
      has been unclear. Advances in imaging technology, such as improved resolution and
      anatomical referencing, allow for more precise regional measurement than
      previously possible. This study explored cerebral glucose metabolism in 17 normal
      controls ranging in age from 20 to 74 years. High resolution PET scanning, with
      MRI-based regions of interest correcting for partial volume and atrophy effects,
      revealed a linear association between advancing age and declining cerebral
      glucose metabolism. The decline averaged 8% per decade for the whole brain.
      Changes were most pronounced in limbic structures, and could be implicated in age
      associated memory loss. 

PMID- 24283818
TI  - Correlates of leukoaraiosis and ventricular enlargement on magnetic resonance
      imaging: a study in normal elderly and cerebrovascular patients.
AB  - Several studies have repeatedly demonstrated that leukoaraiosis as well as
      ventricular enlargement are common findings in normal elderly and in stroke
      patients, although there is no general consensus on prevalence rate as well as on
      their clinical correlations. It is also controversial whether white matter
      changes and ventricular enlargement are reciprocally related. In this study we
      investigated the prevalence and extent of white matter hyperintensities and the
      degree of ventricular enlargement on magnetic resonance imaging in 50 normal
      elderly individuals (mean age 62.1 +/- 7.3 years) and in 50 consecutive chronic
      ischemic stroke patients (mean age 66.1 +/- 7.7 years). All subjects underwent
      extensive clinical assessment. White matter hyperintensities were graded from 0
      to 3 on a semi-quantitative scale, while bifrontal horn, bicaudate, and third
      ventricle ratio indices were used as measures of brain atrophy. Hypertension,
      diabetes, alcohol consumption, cardiac disease, carotid pathology occurred
      significantly more often in patients than in controls. Prevalence rates of white
      matter hyperintensities were 30% in controls and 82% in patients. Patients had
      significantly larger ventricular indices than controls. Significant univariate
      correlations for the extent of white matter hyperintensities were found with age,
      sex, hypertension, cardiac disease, carotid pathology, diabetes, history of
      stroke and ventricular enlargement. Age, sex, cardiac disease, alcohol habit,
      cerebrovascular disease and extent of white matter hyperintensities correlated
      with severity of ventricular enlargement. Multivariate regression analysis
      identified age, hypertension and history of stroke as independent predictors of
      white matter hyperintensities, while history of stroke, age and alcohol
      consumption were found as the only independent predictors of ventricular
      enlargement Separate analysis between periventricular, subcortical or deep white
      matter hyperintensities and each of the three ventricular indices failed to show
      a significant association after adjustment for clinical and demographic factors.
      We suggest that leukoaraiosis and ventricular enlargement are independent
      pathological processes associated with different risk factors in addition to age
      and stroke disease. 

PMID- 24283819
TI  - SEPs N30 amplitude in Parkinson's disease and in pharmacologically induced
      rigidity: relationship with the clinical status.
AB  - The frontal N30 wave amplitude of somatosensory evoked potentials (SEPs) has been
      studied in 41 Parkinson's disease (PD) patients (pts) in a basal condition and
      compared to that of 30 normal subjects; moreover the N30 amplitude and clinical
      motor score have been evaluated in a subgroup of 30 PD pts before and during
      apomorphine infusion and in a second subgroup of 22 PD pts also during levodopa
      chronic therapy. The data show that N30 amplitude is decreased in PD pts in basal
      condition and increased following both treatments by a percentage proportional to
      the clinical improvement Analysis by non parametric correlations showed that the
      increase is well correlated to the clinical score amelioration induced by
      apomorphine in the more affected side. The best correlation was to rigidity score
      amelioration in the group of PD pts in medium stage (Hohen and Yahr stage between
      2 and 3), suggesting a relationship between the rigidity and N30 amplitude
      decrease. Non parkinsonian subjects, treated with low (11 aged normal subjects)
      and high (eight young psychotic pts) doses of antidopaminergic drugs, were
      studied. N30 amplitude decreases were only found in the group of eight psychotic
      pts showing clinical extrapyramidal signs, produced by the high dose of drug
      administered, but not in the group treated with the lower dose not producing
      extrapyramidal side effects, although this dose was efficacious on different
      modalities of evoked potentials. We conclude that N30 amplitude decrease in PD
      reflects the dopaminergic lack paralleled by clinical symptoms. We propose that
      N30 amplitude variations by dopaminergic agonists may be useful in the clinical
      evaluation of dopamine related and non related tone alterations. 

PMID- 24283820
TI  - Dutch normal pressure hydrocephalus study: baseline characteristics with emphasis
      on clinical findings.
AB  - We present the baseline characteristics of 101 patients with normal pressure
      hydrocephalus (NPH), entering a study that evaluates the diagnostic reliability
      of CSF outflow resistance. Patients were assessed by a gait scale consisting of
      10 features of walking and the number of steps and seconds necessary for 10 m, a
      dementia scale comprising the 10 word test, trail making, digit span and finger
      tapping, the modified Mini Mental State Examination (3MSE) and the modified
      Rankin scale (MRS). Inclusion criteria were a gait and dementia scale >= 12
      (range 2-40), a MRS >= 2 and a communicating hydrocephalus on CT. Gait disorder
      and dementia varied from mild to severe leading to MRS 2 in 17%, MRS 3 in 34%,
      MRS 4 in 21%, MRS 5 in 16% and MRS 6, including akinetic mutism, in 12%. Only one
      patient showed both normal tandem walking and turning. Small steps, reduced foot
      floor clearance and wide base were also frequently seen in the 67 patients
      walking independently; 34 needed assistance or could not walk at all. Applying
      the 3MSE, 64% were demented; the remaining 36% exhibited a milder cognitive
      deficit. The 10 word test and trail making decreased with increasing dementia.
      Digit span and finger tapping declined in the most demented patients. This group
      of elderly patients with NPH, mostly of the idiopathic type, proved to be
      vulnerable because of considerable disability and comorbidity. 

PMID- 24283821
TI  - A novel mutation of SOD-1 (Gly 108 Val) in familial amyotrophic lateral
      sclerosis.
AB  - A novel mutation of the SOD-1 gene which encodes the enzyme copper-zinc
      superoxide dismutase was identified in a family manifesting amyotrophic lateral
      sclerosis (ALS) in three generations. The mutation is a heterozygote point
      mutation in exon 4, codon 108 (GGA to GTA), predicting the substitution of valine
      for glycine. The mutation creates a new restriction site for the endonuclease
      AccI. The mutation was demonstrated in two affected members of the family, who
      show features of autosomal dominant inheritance of ALS, but variable age at onset
      ranging from 48 to 72 years. Over 30 different mutations of SOD-1 have now been
      identified in families with ALS. The definition of the different mutations
      causing human disease may allow further investigation of their pathogenicity in
      transgenic animal models, and also offers insight into the variable phenotypic
      disease expression both within and between genotypes. 

PMID- 24283822
TI  - Acute disseminated encephalomyelitis: the importance of early magnetic resonance
      imaging.
AB  - The diagnosis of acute disseminated encephalomyelitis (ADEM) is frequently missed
      or delayed with consequent delay in instituting therapy in the crucial phase of
      the illness. The role of MRI in the diagnosis of ADEM is well established,
      however, the value of its early utilization of treatment on the outcome of
      patients has not been adequately stressed. Three patients with ADEM are
      described. Delay in the diagnosis of the first was associated with severe
      sequelae, while in the other two early diagnosis and institution of
      corticosteroid therapy which was facilitated by MRI, was associated with a better
      outcome. MRI should be carried out early once the diagosis of ADEM is
      entertained. 

PMID- 24283823
TI  - Cytokines and soluble IL-4 in patients with acute optic neuritis and multiple
      sclerosis.
AB  - We measured the cerebrospinal fluid (CSF) and plasma concentrations of
      interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor
      (TNF)-alpha, TNF-beta, interferon (IFN)-gamma, the IL-1 receptor antagonist, and
      soluble IL-4 receptor (sIL-4r) by ELISA in 12 patients each with acute,
      monosymptomatic, idiopathic optic neuritis (ON), ON as part of MS, other attack
      forms of MS, and in neurological control subjects. CSF concentrations of IL
      1beta, IL-2 and IFN-gamma differed significantly between the different patient
      groups and were detected most commonly at the highest concentrations in patients
      with non-ON attacks of MS. TNF-beta was detected exclusively in CSF from
      neurological control patients. The patients with non-ON attacks of MS also had
      significantly elevated concentrations of sIL-4r in plasma. Increased CSF
      concentrations of IL-1beta, IL-2 and IFN-gamma together with increased plasma
      concentrations of sIL-4r support the concept of MS as an autoimmune disease with
      preferential activation of proinflammatory or T-helper type 1-like cells.
      Patients with idiopathic ON or ON as part of MS may, however, differ
      immunologically from patients with other attack forms of MS. 

PMID- 24283824
TI  - Botulinum toxin type A in cerebellar tremor caused by multiple sclerosis.
AB  - The intention tremor seen in chronic progressive multiple sclerosis is often
      disabling and existing treatments are of limited benefit The present pilot study
      was designed to assess the role of Botulinum toxin type A (BOTOX(r)) in such
      cases. Five patients with the condition received 40 mouse units of toxin into the
      flexor and extensor compartments of the forearm. Two of these went on to receive
      a further 100 mouse units 2 months after the previous injection. Tremor was
      assessed at 0, 2 and 8 weeks post-injection using a validated clinical rating
      scale, spirography and handwriting samples, and a clinician's global rating
      scale; functional capacity was measured using an activities of daily living (ADL)
      scale adapted for use in tremor. No statistically significant improvement
      occurred in intention tremor, although there was a trend toward a mild
      improvement in the clinician's global rating scale. Patients noted an increase in
      their pre-existing corticospinal weakness which proved to be dose-limiting. No
      change occurred in ADL scores. It is concluded that pre-existing weakness limits
      the use of Botulinum toxin in the intention tremor seen in multiple sclerosis,
      but further work in disabling primary and secondary cerebellar degenerations
      without corticospinal weakness may be worthwhile. 

PMID- 24283825
TI  - Fatigue in multiple sclerosis is not due to sleep apnoea.
AB  - Fatigue is a frequent and disabling phenomenon among patients with multiple
      sclerosis (MS). Daytime sleepiness is a typical symptom of the sleep
      apnoea/hypopnoea syndrome due to nocturnal hypoxia and recurrent arousals causing
      sleep fragmentation. Since MS plaques are often found in the midbrain, brain stem
      and upper cervical cord on magnetic resonance imaging (MRI) we hypothesized that
      fatigue in MS patients might be caused by a central respiratory dysfunction. We
      investigated 10 patients with definite MS by oligography, two questionnaires
      assessing fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth
      Sleepiness Scale, ESS), MRI and pulmonary function tests. A total of six patients
      had either an elevated FSS and/or an elevated ESS. None of the six patients with
      an elevated FSS and/or ESS has an apnoea index > 5/hour. CT90 was normal in nine
      patients. We conclude that fatigue and daytime sleepiness in MS cannot be
      explained by nocturnal apnoeas or oxygen desaturations. The Fatigue Severity
      Scale should be integrated to the extended Barthel index, which is a new
      instrument for disability assessment in MS patients. 

PMID- 24283826
TI  - Change in the pattern of cervical dystonia might be the cause of benefit loss
      during botulinum toxin treatment.
AB  - The muscular patterns of cervical dystonia were identified by polymyographic
      recordings in 76 patients before botulinum toxin treatment. The leading muscles
      were considered to be those which started dystonic movement and which showed
      constant and maximal activity during all dystonic movements. The dystonic muscles
      were repeatedly treated by local Injections of botulinum toxin. Sixteen patients
      showed (after repeated injections) loss of the benefit of local applications of
      botulinum toxin after various periods of time. Repeated polymyographic recordings
      were performed in these patients during the loss of the benefit of injected
      botulinum toxin. In four patients repeated polymyographic recordings showed an
      Identical pattern of cervical dystonia, but the activity of previously injected
      muscles was apparently decreased. In 12 patients only minimum or no activity was
      recorded in muscles which had previously been treated with botulinum toxin, but
      the pattern of cervical dystonia was changed. Different patterns of cervical
      dystonia with different leading muscles, but with identical directions of head
      deviation, were observed in six patients. In another six patients, the head
      deviation direction was to the opposite side and was accompanied by a change of
      the leading muscle and a change of the muscular pattern of dystonia. These
      results suggest either that dystonic activity from the cerebral generator changes
      to new effectors during the peripheral blockade of primary dystonic muscles, or
      that a change of generators at different levels of the CNS occurs. It may be
      neccessary to carry out repeated polymyographic recordings throughout the period
      of loss of benefit of previously successful local botulinum toxin injections. 

PMID- 24283827
TI  - Magnetic resonance imaging in a case of migraine with ophthalmoplegia.
AB  - We present the case of a migrainous girl who suffered an episode of migraine-like
      headache associated with ophthalmoplegia. MRI showed reversible enhancement and
      thickening of the cisternal portion of the oculomotor nerve. This finding
      suggests a mechanism different from diabetic ischaemic neuropathy, as similar MRI
      abnormalities were rarely reported in diabetic ophthalmoplegia. The MRI findings
      are most in favour of an inflammatory cause. 

PMID- 24283828
TI  - Streptococcus salivarius meningitis: a case report and literature review.
AB  - Twelve hours after spinal anaesthesia, a 61-year-old patient developed meningitis
      with fever, somnolence, headache and stiffness of the neck. The cerebrospinal
      fluid was found to contain 5.279/mm(3) cells (95 granulocytes), 12.800 mg/l
      protein and 14.0 mmol/l lactate. Streptococcus salivarius was detected in the
      culture. The patient was treated with antibiotics (initially cefotaxime,
      fosfomycin and gentamycin, later piperacillin and sulbactam). Restitutio ad
      integrum took place after 7 days. Thirteen cases of Streptococcus salivarius
      meningitis over the past 40 years are described in the literature, nine of which
      occurred following spinal puncture. Streptococcus salivarius was probably
      communicated by the medical personnel from the oral cavity when working without
      masks. The outcome in each case was good. In our opinion suitable masks must be
      worn during spinal puncture. Although iatrogenic infection is uncommon, it cannot
      be ruled out. 

PMID- 24283829
TI  - Isolated palilalia: a case report.
AB  - We report the case of a 74-year-old patient, whose spontaneous speech was
      characterized by the compulsive repetition of parts of words, words and sentences
      with increasing rate and decreasing loudness. On a standardized language
      examination, his performance was within normal limits, besides the presence of
      palilalia; neurological examination showed a slight limitation of vertical gaze
      and a reduction of blinking. A small right capsulo-thalamic ischemic lesion was
      present on magnetic resonance imaging. This case provides further evidence that
      palilalia can be observed as an isolated impairment of speech production
      following subcortical lesions. 

PMID- 24283830
TI  - Do people with HIV infection have a normal life expectancy in the era of
      combination antiretroviral therapy?
AB  - There is evidence that the life expectancy (LE) of individuals infected with the
      human immunodeficiency virus (HIV) has increased since the introduction of
      combination antiretroviral therapy (cART). However, mortality rates in recent
      years in HIV-positive individuals appear to have remained higher than would be
      expected based on rates seen in the general population. A low CD4 count, whether
      due to late HIV diagnosis, late initiation of cART, or incomplete adherence to
      cART, remains the dominant predictor of LE, and thus the individual's disease
      stage at initiation of cART (or thereafter) certainly contributes to these higher
      mortality rates. However, individuals with HIV also tend to exhibit lifestyles
      and behaviors that place them at increased risk of mortality, particularly from
      non-AIDS causes. Thus, although mortality rates among the HIV population may
      indeed remain slightly higher than those seen in the general population, they may
      be no higher than those seen in a more appropriately matched control group. Thus,
      further improvements in LE may now only be possible if some of the other
      underlying issues (for example, modification of lifestyle or behavioral factors)
      are tackled.

PMID- 24283831
TI  - The von Willebrand factor predicted unpaired cysteines are essential for
      secretion.
AB  - BACKGROUND: von Willebrand factor (VWF) contains free thiols that mass
      spectroscopy has located to nine cysteines: two in the D3 domain (Cys889 and
      Cys898) and seven in the C domains (Cys2448, Cys2451, Cys2453, Cys2490, Cys2491,
      Cys2528, and Cys2533) (J Biol Chem, 7, 2007, 35604; Blood, 118, 5312). It has
      been suggested that these free thiols function to regulate the self-association
      of VWF through thiol-disulfide exchange (J Biol Chem, 7, 2007, 35604; Blood, 118,
      5312). However, recent structural modeling has predicted that these cysteines
      are, in fact, disulfide-bonded (Blood, 118, 5312; Blood, 120, 449). OBJECTIVES:
      To use mutation and expression analyses to investigate how these conflicting
      reports might be compatible with the synthesis and expression of VWF. METHODS AND
      RESULTS: Both full-length VWF and VWF fragments with cysteine to alanine
      mutations of the nine cysteines and two predicted binding partners (Cys2431 and
      Cys2468) failed to secrete. Mutation of a cysteine pair, C2431A/C2453A, similarly
      resulted in a failure to secrete, indicating that this is not secondary to
      creation of an unpaired thiol. Deletion mutants containing seven of these
      cysteines, conforming to hypothesized domain boundaries, also failed to secrete:
      ?C1C6 (2255-2720), ?C3C4 (2429-2577), ?C3 (2429-2496), and ?C4 (2497-2577).
      Analysis of cell lysates and immunofluorescence confirmed that the mutants were
      retained within the endoplasmic reticulum (ER). Coexpression with wild-type VWF
      rescued secretion of some mutants to a limited extent. CONCLUSIONS: These data
      suggest: first, that pairing of cysteines implicated in free thiol exchange is
      essential for correct folding of the VWF molecule, and unpairing must occur
      following exit from the ER or secretion from the cell; and second, that intact C
      domains are essential for efficient VWF secretion and must interact in the ER.

PMID- 24283832
TI  - Taxonomic uncertainty and the loss of biodiversity on Christmas Island, Indian
      Ocean.
AB  - The taxonomic uniqueness of island populations is often uncertain which hinders
      effective prioritization for conservation. The Christmas Island shrew (Crocidura
      attenuata trichura) is the only member of the highly speciose eutherian family
      Soricidae recorded from Australia. It is currently classified as a subspecies of
      the Asian gray or long-tailed shrew (C. attenuata), although it was originally
      described as a subspecies of the southeast Asian white-toothed shrew (C.
      fuliginosa). The Christmas Island shrew is currently listed as endangered and has
      not been recorded in the wild since 1984-1985, when 2 specimens were collected
      after an 80-year absence. We aimed to obtain DNA sequence data for cytochrome b
      (cytb) from Christmas Island shrew museum specimens to determine their taxonomic
      affinities and to confirm the identity of the 1980s specimens. The Cytb sequences
      from 5, 1898 specimens and a 1985 specimen were identical. In addition, the
      Christmas Island shrew cytb sequence was divergent at the species level from all
      available Crocidura cytb sequences. Rather than a population of a widespread
      species, current evidence suggests the Christmas Island shrew is a critically
      endangered endemic species, C. trichura, and a high priority for conservation. As
      the decisions typically required to save declining species can be delayed or
      deferred if the taxonomic status of the population in question is uncertain, it
      is hoped that the history of the Christmas Island shrew will encourage the
      clarification of taxonomy to be seen as an important first step in initiating
      informed and effective conservation action. 

PMID- 24283833
TI  - HER2 and immunotherapy using monoclonal antibodies in colorectal cancer.

PMID- 24283834
TI  - Striving for synergy: how to improve cancer immunotherapy through multiple
      agonist costimulation.

PMID- 24283835
TI  - New therapeutic could help prevent hypersensitive allergic reactions.

PMID- 24283837
TI  - Tandem myeloablative 131I-rituximab radioimmunotherapy and high-dose chemotherapy
      in refractory/relapsed non-Hodgkin lymphoma patients.
AB  - This Phase I/II study investigated myeloablative (131)I-rituximab
      radioimmunotherapy (RIT) and high-dose chemotherapy supported by one or two
      autologous stem cell transplantations in heavily pretreated patients with
      relapsed or refractory B cell non-Hodgkin lymphoma. Myeloablative RIT was safe
      and feasible when followed by autologous stem cell transplantation with low
      incidence of secondary late effects and could be a reasonable alternative regimen
      especially in elderly patients and in patients who have concerns about high-dose
      chemotherapy. Tandem myeloablative (131)I-rituximab RIT and high-dose
      chemotherapy supported by two autologous stem cell transplantations was also
      feasible. However, the toxicity was higher than after myeloablative RIT,
      therefore it might be recommended to restrict the tandem approach to lymphoma
      with poor prognosis.

PMID- 24283836
TI  - Interview: immunotherapeutic manipulation of the tumor microenvironment.

PMID- 24283838
TI  - Reprogramming donor T cells for adoptive immunotherapy.

PMID- 24283839
TI  - Understanding myeloma cancer stem cells.

PMID- 24283840
TI  - Is faster safer? Cluster versus short conventional subcutaneous allergen
      immunotherapy.
AB  - AIM: Few studies have compared cluster immunotherapy and conventional
      administration regimens. The aim of this study was to establish the safety
      profile of these different regimens in patients with allergic respiratory
      diseases who received index-of-reactivity (IR)-standardized allergen extracts by
      the subcutaneous route. MATERIALS & METHODS: The safety of subcutaneous
      immunotherapy (SCIT), administered by means of a 4-week cluster titration
      schedule (cluster-SCIT) or by an 8-week short conventional titration schedule (SC
      SCIT), both with a target dose of 8 IR, was assessed in a retrospective,
      observational, multicenter study. RESULTS: A total of 658 patients (339 cluster
      SCIT and 319 SC-SCIT) were recruited from 92 sites in Spain. Injection site
      reactions occurred in 25.1 and 27.3% of patients treated with cluster-SCIT and SC
      SCIT, respectively. Systemic reactions (European Academy of Allergy and Clinical
      Immunology criteria) were reported for 0.2% of doses and 1.5% of patients with
      cluster-SCIT, and 0.7% of doses and 4.4% of patients with SC-SCIT. Most reactions
      were mild and there were no grade 3 or 4 systemic reactions. No life-threatening
      systemic reactions, anaphylactic shock, or adverse events leading to therapy
      discontinuation were reported. CONCLUSION: The safety profile of the cluster
      regimen supports the use of accelerated SCIT schedules with IR-standardized
      allergen extracts compared with short conventional schedules, particularly if
      similar extracts and application methods are used.

PMID- 24283841
TI  - Autologous and allogenic systems of HIV expansion: what is the better choice for
      clinical application in therapeutic vaccine?
AB  - AIMS: HIV-1 expanded in an allogenic system (Al-HIV) represents a cheaper and
      faster alternative to the autologous virus (Au-HIV) as an antigen in anti-HIV
      immunotherapy. In this study, chemically inactivated HIV-1 obtained through
      autologous or allogenic systems were compared. PATIENTS & METHODS: Au-HIV and Al
      HIV obtained from cultures of peripheral blood mononuclear cells from 11 HIV(+)
      individuals were tested for virus production, yield and time of culture, and
      their ability to elicit a specific immune response in vitro. RESULTS: The
      allogenic system was more efficient than the autologous system. Dendritic cells
      pulsed with Au-HIV and Al-HIV presented a similar phenotypic profile, but only Al
      HIV induced a significant increase in IFN-gamma(+) lymphocytes. CONCLUSION: The
      use of an allogenic system displays several advantages in terms of cell
      manipulation, time and cost of culture, and immunogenicity.

PMID- 24283843
TI  - Recombinant allergens for pollen immunotherapy.
AB  - Specific immunotherapy (IT) represents the only potentially curative therapeutic
      intervention of allergic diseases capable of suppressing allergy-associated
      symptoms not only during treatment, but also after its cessation. Presently, IT
      is performed with allergen extracts, which represent a heterogeneous mixture of
      allergenic, as well as nonallergenic, compounds of a given allergen source. To
      overcome many of the problems associated with extract-based IT, strategies based
      on the use of recombinant allergens or derivatives thereof have been developed.
      This review focuses on recombinant technologies to produce allergy
      therapeuticals, especially for allergies caused by tree, grass and weed pollen,
      as they are among the most prevalent allergic disorders affecting the population
      of industrialized societies. The reduction of IgE-binding of recombinant allergen
      derivatives appears to be mandatory to increase the safety profile of vaccine
      candidates. Moreover, increased immunogenicity is expected to reduce the dosage
      regimes of the presently cumbersome treatment. In this regard, it has been
      convincingly demonstrated in animal models that hypoallergenic molecules can be
      engineered to harbor inherent antiallergenic immunologic properties. Thus,
      strategies to modulate the allergenic and immunogenic properties of recombinant
      allergens will be discussed in detail. In recent years, several successful
      clinical studies using recombinant wild-type or hypoallergens as active
      ingredients have been published and, currently, novel treatment forms with higher
      safety and efficacy profiles are under investigation in clinical trials. These
      recent developments are summarized and discussed. 

PMID- 24283842
TI  - Employing an IL-23 p19 vaccine to block IL-23 ameliorates chronic murine colitis.
AB  - BACKGROUND: Overexpression of IL-23 has been implicated in the pathogenesis of
      Crohn's disease. Using vaccines to block overexpressed endogenous cytokines has
      emerged as a new therapeutic strategy for the long-term treatment of the disease.
      AIM: We sought to develop peptide-based vaccines specific to IL-23 and evaluate
      their effects in colitis mice. MATERIALS & METHODS: The vaccine was developed by
      inserting a peptide derived from mouse IL-23 p19 into the carrier protein,
      hepatitis B core antigen, using molecular engineering methods. One vaccine
      against IL-23 p19 was obtained that induced high-titered and long-lasting
      antibodies to IL-23 without the use of adjuvants. The inhibitory effect of
      vaccine-immunized serum was subsequently evaluated in vitro. To evaluate the in
      vivo effects, mice were subcutaneously injected with the vaccine, carrier or
      saline three times. Two weeks after the last injection, chronic colitis was
      induced in mice by seven weekly administrations with 2,4,6-trinitrobenzene
      sulfonic acid. RESULTS: In vitro studies revealed that serum IL-23 p19-specific
      IgG significantly suppressed IL-23-induced IL-17 production by splenocytes. In
      vivo evaluation of the effect of the vaccine in mice with chronic colitis
      indicated that vaccine-immunized mice exhibited a decrease in colon inflammation,
      collagen deposition and levels of IL-23 and IL-12 cytokines, compared with
      control groups. CONCLUSION: IL-23 p19 vaccine is capable of downregulating
      inflammatory responses in chronic murine colitis, providing a novel therapeutic
      approach in Crohn's disease.

PMID- 24283844
TI  - Local reactions from subcutaneous allergen immunotherapy.
AB  - Local reactions from subcutaneous allergen immunotherapy are very common during
      the course of immunotherapy. These local reactions are not bothersome to
      patients. Local reactions from immunotherapy also do not predict future local or
      systemic reactions. This review discusses the studies that show that local
      reactions are not predictive of future reactions and that dose adjustments for
      local reactions from allergen immunotherapy are unnecessary. The article also
      focuses on factors that lead to patient noncompliance with immunotherapy and
      evaluates methods to prevent local reactions from subcutaneous allergen
      immunotherapy. 

PMID- 24283845
TI  - Targeting castration-resistant prostate cancer with monoclonal antibodies and
      constructs.
AB  - Antibodies administered either alone or in a unique construct that can enhance
      targeting, immunologic recognition and cell killing, remain an area of active
      interest for a variety of solid tumors. Prostate cancer has unique
      characteristics as a target for immune-mediated therapies, particularly since it
      has not only a wide array of antigens expressed on its cell surface, but also has
      an associated biomarker, which not only can monitor the disease status but also
      its response to therapy. A number of unique cell surface antigens, as well as
      internally mediated cell molecules, have shown their clinical activity and
      efficacy as prostate cancer treatments. The continued evolution of novel antibody
      drug and antibody-imaging constructs will probably offer more efficient ways to
      deliver a therapeutic to the tumor and enhance imaging of active or treated sites
      of disease. 

PMID- 24283847
TI  - International Phase III clinical trial demonstrates efficacy of a new second-line
      drug for gastric cancer.

PMID- 24283848
TI  - Cation and anion dependence of stable geometries and stabilization energies of
      alkali metal cation complexes with FSA(-), FTA(-), and TFSA(-) anions:
      relationship with physicochemical properties of molten salts.
AB  - Stable geometries and stabilization energies (Eform) of the alkali metal
      complexes with bis(fluorosulfonyl)amide,
      (fluorosulfonyl)(trifluoromethylslufonyl)amide and
      bis(trifluoromethylsulfonyl)amide (FSA(-), FTA(-) and TFSA(-)) were studied by ab
      initio molecular orbital calculations. The FSA(-) complexes prefer the bidentate
      structures in which two oxygen atoms of two SO2 groups have contact with the
      metal cation. The FTA(-) and TFSA(-) complexes with Li(+) and Na(+) prefer the
      bidentate structures, while the FTA(-) and TFSA(-) complexes with Cs(+) prefer
      tridentate structures in which the metal cation has contact with two oxygen atoms
      of an SO2 group and one oxygen atom of another SO2 group. The two structures are
      nearly isoenergetic in the FTA(-) and TFSA(-) complexes with K(+) and Rb(+). The
      magnitude of Eform depends on the alkali metal cation significantly. The Eform
      calculated for the most stable TFSA(-) complexes with Li(+), Na(+), K(+), Rb(+)
      and Cs(+) cations at the MP2/6-311G** level are -137.2, -110.5, -101.1, -89.6,
      and -84.1 kcal/mol, respectively. The viscosity and ionic conductivity of the
      alkali TFSA molten salts have strong correlation with the magnitude of the
      attraction. The viscosity increases and the ionic conductivity decreases with the
      increase of the attraction. The melting points of the alkali TFSA and alkali BETA
      molten salts also have correlation with the magnitude of the Eform, which
      strongly suggests that the magnitude of the attraction play important roles in
      determining the melting points of these molten salts. The anion dependence of the
      Eform calculated for the complexes is small (less than 2.9 kcal/mol). This shows
      that the magnitude of the attraction is not the cause of the low melting points
      of alkali FTA molten salts compared with those of corresponding alkali TFSA
      molten salts. The electrostatic interactions are the major source of the
      attraction in the complexes. The electrostatic energies for the most stable TFSA(
      ) complexes with the five alkali metal cations are -140.3, -119.4, -104.1, -96.9,
      and -91.1 kcal/mol, respectively. The induction interactions also contribute to
      the attraction. In particular, the induction interactions are large in the Li(+)
      complexes. The induction energies for the five complexes are -46.6, -25.2, -17.5,
      -13.3, and -10.4 kcal/mol, respectively. 

PMID- 24283846
TI  - Influence of host immunoregulatory genes, ER stress and gut microbiota on the
      shared pathogenesis of inflammatory bowel disease and Type 1 diabetes.
AB  - Inflammatory bowel disease (IBD) with its two distinct entities, Crohn's disease
      and ulcerative colitis, and Type 1 diabetes mellitus (T1D) are autoimmune
      diseases. The prevalence of these diseases continues to rapidly rise in the
      industrialized world. Despite the identification of several genetic loci that are
      associated with both IBD and T1D, thus far, there is a paucity of epidemiological
      data to support a clinical overlap. In an effort to better understand the
      underlying pathogenic mechanisms of both IBD and T1D, this review summarizes the
      literature about these related autoimmune diseases, describes the most recent
      advances in their etiopathogenesis and emphasizes the genetic and nongenetic
      factors that exercise a differential influence. Genome-wide association studies
      have identified genetic loci with a role in immune response regulation that are
      linked to both IBD (particularly Crohn's disease) and T1D. Some of these genetic
      loci (e.g., IL-18RAP) have a divergent role, conferring risk for one disease and
      protection for the other. Recent evidence highlights an important role of gut
      microbiota and cellular responses (e.g., endoplasmic reticulum stress) in the
      pathogenesis of both IBD and T1D. 

PMID- 24283849
TI  - Transferring functional annotations of membrane transporters on the basis of
      sequence similarity and sequence motifs.
AB  - BACKGROUND: Membrane transporters catalyze the transport of small solute
      molecules across biological barriers such as lipid bilayer membranes.
      Experimental identification of the transported substrates is very tedious. Once a
      particular transport mechanism has been identified in one organism, it is thus
      highly desirable to transfer this information to related transporter sequences in
      different organisms based on bioinformatics evidence. RESULTS: We present a
      thorough benchmark at which level of sequence identity membrane transporters from
      Escherichia coli, Saccharomyces cerevisiae, and Arabidopsis thaliana belong to
      the same families of the Transporter Classification (TC) system, and at what
      level these membrane transporters mediate the transport of the same substrate. We
      found that two membrane transporter sequences from different organisms that are
      aligned with normalized BLAST expectation value better than E-value 1e-8 are
      highly likely to belong to the same TC family (F-measure around 90%). Enriched
      sequence motifs identified by MEME at thresholds below 1e-12 support accurate
      classification into TC families for about two thirds of the sequences (F-measure
      80% and higher). For the comparison of transported substrates, we focused on the
      four largest substrate classes of amino acids, sugars, metal ions, and phosphate.
      At similar identity thresholds, the nature of the transported substrates was more
      divergent (F-measure 40--75% at the same thresholds) than the TC family
      membership. CONCLUSIONS: We suggest an acceptable threshold of 1e-8 for BLAST and
      HMMER where at least three quarters of the sequences are classified according to
      the TC system with a reasonably high accuracy. Researchers who wish to apply
      these thresholds in their studies should multiply these thresholds by the size of
      the database they search against. Our findings should be useful to those who wish
      to transfer transporter functional annotations across species.

PMID- 24283850
TI  - A survey of 165 sporotrichosis cases examined in Nagasaki prefecture from 1951 to
      2012.
AB  - A total of 165 sporotrichosis cases occurring in Nagasaki prefecture, and
      examined at Nagasaki University Hospital, were evaluated. Both males and females
      were equally affected, with no significant differences in the affected body
      regions. Lesions were frequently seen on the face (49 cases, 29.5%) and upper
      limbs (101 cases, 60.9%). The localised cutaneous type of sporotrichosis (105
      cases, 62.9%) was much more frequent than the lymphocutaneous type (62 cases,
      37.1%). The infection rate in patients over 50 years of age was 73.1%. The most
      frequent occupation among the patients was farming (52 cases, 37.4%), and 34
      patients had a history of injury. Regarding the geographical distribution of
      sporotrichosis, 48 cases occurred in the Shimabara peninsula (31.2%) and this is
      much higher than expected for the population size. Before 1994, almost all
      sporotrichosis cases (112 cases, 96.5%) were treated with potassium iodide (KI).
      After 1995, the number of patients treated with KI decreased (nine cases, 23.1%),
      and itraconazole (ITZ) was used in 21 cases (59.0%) and terbinafine in six cases
      (15.3%). The time between ITZ and KI treatment and cure was 13.8 weeks and 12.5
      weeks, respectively. All 116 cases, for which the outcome was known, were cured
      or improved. 

PMID- 24283851
TI  - Current approach to masked hypertension: From diagnosis to clinical management.
AB  - The term 'masked hypertension phenomenon' was first described by the late
      Professor Thomas Pickering and is commonly defined as having a normal clinic
      blood pressure (BP) but an elevated 'out of office' reading. In the main, these
      elevated readings have been provided through ambulatory BP monitoring (ABPM), but
      sometimes home BP monitoring is used. It is now largely accepted that ABPM gives
      a better classification of risk than clinic BP. Thus, the elevated ABPM levels
      should relate to higher cardiovascular risk, and it follows that these people may
      be regarded as being genuinely hypertensive and at higher cardiovascular risk.
      The problem for clinical practice is how to identify and manage these
      individuals. The phenomenon should be suspected in individuals who have had an
      elevated clinic BP at some time, in young individuals with normal or normal-high
      clinic BP who have early left ventricular hypertrophy, in individuals with a
      family history of hypertension in both parents, patients with multiple risks for
      cardiovascular disease and perhaps diabetic patients. Masked hypertension appears
      to be more prevalent in individuals of male gender, with younger age, higher
      heart rate, obesity or high cholesterol levels and in smokers. Those with masked
      hypertension are at higher risk of events such as stroke and have a higher
      prevalence of target organ damage, for example, nephropathy. In conclusion, most
      of the debate around this topic relates to its reliable identification. Given the
      higher ambulatory mean blood pressure values there is an increased cardiovascular
      risk making this diagnosis important.

PMID- 24283853
TI  - The "sprinkling" sign in the follicular variant of papillary thyroid carcinoma: a
      clue to the recognition of this entity.

PMID- 24283854
TI  - Comparison of Classic and International Society of Urological Pathology 2005
      Modified Gleason grading using needle biopsies from the Reduction by Dutasteride
      of Prostate Cancer Events (REDUCE) trial.
AB  - CONTEXT: Use of the International Society of Urological Pathology (ISUP) 2005
      modified Gleason score may result in higher scores compared with the classic
      Gleason scoring system. OBJECTIVE: To compare scores derived using the 2 scoring
      systems. DESIGN: On-study and for-cause biopsies were centrally reviewed and
      assigned a classic Gleason score in the Reduction by Dutasteride of prostate
      Cancer Events trial. Positive biopsies were reviewed by an independent
      pathologist in a secondary review using the ISUP 2005 modified Gleason score. The
      independent pathologist also recorded a classic Gleason score. RESULTS: In total,
      1482/1507 (98%) positive biopsy results were independently reviewed. Scores
      assigned by the 2 pathologists (classic versus modified) agreed in 83% (1230 of
      1481) of cases; 99% (1471 of 1481) of cancers were within +/-1 of their previous
      score. Of discordant cases, similar numbers of biopsies were upgraded and
      downgraded in the secondary review, with minor differences in the score
      distributions. Interobserver agreement was good, with kappa values ranging from
      0.62 (95% confidence interval [CI], 0.56-0.67) to 0.70 (95% CI, 0.65-0.76). The
      overall number of high-grade tumors (Gleason score 8-10; n = 48) remained
      constant between reviews, with 3 fewer cases in the placebo group (n = 16) and 3
      more in the dutasteride group (n = 32) in the secondary review. When comparing
      the independent pathologist's modified scores versus the classic, 17 of 1481
      cancers (1.1%) were upgraded (including 9 of 17 upgrades [53%] to high-grade
      tumors). CONCLUSIONS: This analysis showed similar score distributions between
      the classic and modified Gleason scoring systems. The differences seen between
      the 2 pathologists' scores likely reflect differences in interpretation rather
      than the scoring system chosen.

PMID- 24283855
TI  - Inpatient preanalytic process improvements.
AB  - CONTEXT: Phlebotomy services are a common target for preanalytic improvements.
      Many new, quality engineering tools have recently been applied in clinical
      laboratories. However, data on relatively few projects have been published. This
      example describes a complete application of current, quality engineering tools to
      improve preanalytic phlebotomy services. OBJECTIVES: To decrease the response
      time in the preanalytic inpatient laboratory by 25%, to reduce the number of
      incident reports related to preanalytic phlebotomy, and to make systematic
      process changes that satisfied the stakeholders. DESIGN: The Department of
      Laboratory Medicine, General Services Section, at the University of Texas MD
      Anderson Cancer Center (Houston) is responsible for inpatient phlebotomy in a 24
      hour operation, which serves 689 inpatient beds. The study director was project
      director of the Division of Pathology and Laboratory Medicine's Quality
      Improvement Section and was assisted by 2 quality technologists and an industrial
      engineer from MD Anderson Office of Performance Improvement. RESULTS: After
      implementing each solution, using well-recognized, quality tools and metrics, the
      response time for blood collection decreased by 23%, which was close to meeting
      the original responsiveness goal of 25%. The response time between collection and
      arrival in the laboratory decreased by 8%. Applicable laboratory-related incident
      reports were reduced by 43%. CONCLUSIONS: Comprehensive application of quality
      tools, such as statistical control charts, Pareto diagrams, value-stream maps,
      process failure modes and effects analyses, fishbone diagrams, solution
      prioritization matrices, and customer satisfaction surveys can significantly
      improve preset goals for inpatient phlebotomy.

PMID- 24283856
TI  - High expression of H3K9me3 is a strong predictor of poor survival in patients
      with salivary adenoid cystic carcinoma.
AB  - CONTEXT: Histone methylation and acetylation play important roles in the
      carcinogenesis and progression of cancer. OBJECTIVE: To investigate whether
      histone modifications influence the prognosis of patients with salivary adenoid
      cystic carcinoma (ACC). DESIGN: The expression of histone H3 lysine 9
      trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was
      assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used
      to determine the presence of any correlation between H3K9me3 and H3K9Ac levels
      and clinicopathologic parameters. Log-rank test and Cox proportional hazards
      regression models were used to analyze the survival data. RESULTS: H3K9me3
      expression was positively correlated with solid pattern tumors (P = .002) and
      distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression
      levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors
      showed high H3K9me3 expression and a solid pattern had a significantly poorer
      overall survival (OS) (P < .001 and P < .001, respectively) and disease-free
      survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was
      correlated with poor OS (P = .05). The multivariate analysis indicated that high
      levels of H3K9me3 expression and solid pattern tumors were independent prognostic
      factors that significantly influenced OS (P = .004 and P = .04, respectively).
      H3K9me3 expression was identified as the only independent predictor of disease
      free survival (P = .006). CONCLUSIONS: Our results suggest that high levels of
      H3K9me3 expression are predictive of rapid cell proliferation and distant
      metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better
      predictive biomarker for the prognosis of patients with salivary ACC.

PMID- 24283857
TI  - Reducing false-negative and false-positive diagnoses in anatomic pathology
      consultation material.
AB  - CONTEXT: Previous studies have shown that there are disagreements in
      interlaboratory consultation, including false-negative and false-positive
      diagnoses. To date, methods to reduce false-negative and false-positive diagnoses
      have been poorly documented. OBJECTIVE: To identify features associated with
      false-negative and false-positive diagnoses in anatomic pathology. DESIGN: We
      reviewed the results of interlaboratory consultation in our institution during a
      9-year period. For false-negative and false-positive diagnoses, methods that
      might have prevented the error were identified. RESULTS: Disagreements were
      identified in 810 of 8082 consults (10%). Fifty-four false-negative cases (0.7%
      of all consults) and 27 false-positive cases (0.3%) were identified. False
      negative cases were more common in breast (20 of 1131; 1.8%), genitourinary (16
      of 970; 1.7%), hematologic (3 of 242; 1.3%), and cytology (3 of 404; 0.8%) than
      in all other sites combined (P < .001); no significant difference in sites were
      identified for false-positive cases. Overall, there was no difference in the
      percentage of cases that were reviewed by more than one pathologist in either
      false-negative cases (109 of 810; 13.5%) or false-positive cases (135 of 810;
      16.7%), compared with all other consults (858 of 7272; 11.8%) (P = .74 and .59,
      respectively). However, on review, 12 of all 27 false-positive cases (44%) might
      have been prevented by the use of immunohistochemistry alone, and 36 of all 54
      false-negative cases (67%) might have been prevented by the use of a second
      review; special stains, including immunohistochemistry; additional levels;
      changes in processing; and hedges. CONCLUSION: Approximately one-half of false
      negative and false-positive cases (48 of 81; 59%) might be preventable by the use
      of a combination of pathologic methods.

PMID- 24283858
TI  - Sampling modality influences the predictive value of grading in adult soft tissue
      extremity sarcomas.
AB  - CONTEXT: Histologic grade is one of the best predictors of outcome in adult soft
      tissue sarcomas. Current grading systems were validated on resection specimens;
      however, there has been a trend toward the use of biopsies to diagnosis these
      tumors. OBJECTIVES: To determine whether the grade of an extremity soft tissue
      sarcoma determined on tissue obtained by either core needle biopsy or incisional
      biopsy is predictive of metastasis- or disease-free survival, and whether either
      sampling modality is superior. DESIGN: One hundred three core needle biopsies and
      107 incisional biopsies of nonmetastatic spindle cell sarcomas of the extremities
      were retrieved from the archives. All cases had a minimum 2-year follow-up.
      Patient data and outcome and tumor characteristics were recorded. Tumors were
      reviewed and evaluated using the French Federation of Cancer Centers Sarcoma
      Group grading system. Kaplan-Meier survival curves were generated to correlate
      tumor grade with metastasis- and disease-free survival for both groups. RESULTS:
      Patient and tumor characteristics were similar between groups except that more
      tumors were grade 3 and superficial in the incisional biopsy group. Grade
      determined on core needle biopsy was not predictive of either metastasis-free
      survival (P = .59) or disease-free survival (P = .50). In contrast, grade
      determined on incisional biopsy was predictive of both metastasis-free survival
      (P < .001) and disease-free survival (P = .001). CONCLUSIONS: Biopsy,
      particularly core needle biopsy, represents a convenient diagnostic tool,
      particularly in the context of neoadjuvant therapy. However, based on these
      results incisional biopsy is recommended if grading is to be used to predict
      prognosis in spindle cell soft tissue sarcomas of the extremities.

PMID- 24283859
TI  - Distribution of low-density lipoprotein and high-density lipoprotein subclasses
      in patients with sarcoidosis.
AB  - CONTEXT: Systemic inflammatory diseases are associated with proatherogenic
      lipoprotein profile, but there is a lack of information regarding overall
      distributions of lipoprotein subclasses in sarcoidosis. OBJECTIVE: To investigate
      whether patients with sarcoidosis have altered distributions of plasma low
      density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. DESIGN:
      Seventy-seven patients with biopsy-proven sarcoidosis (29 with acute and 48 with
      chronic sarcoidosis) treated with corticosteroids and 77 age- and sex-matched
      controls were included in the study. Low-density lipoprotein and HDL subclasses
      were determined by gradient gel electrophoresis, while inflammatory markers and
      lipid parameters were measured by standard laboratory methods. RESULTS: Compared
      to controls, patients had fewer LDL I subclasses (P < .001), but more LDL II and
      III (P < .001) subclasses. This pattern was evident in both acute and chronic
      disease groups. Patients also had smaller HDL size (P < .001) and higher
      proportions of HDL 2a (P = .006) and 3a particles (P = .004). Patients with
      chronic sarcoidosis had smaller LDL size than those with acute disease (P = .02)
      and higher proportions of HDL 3a subclasses (P = .04) than controls. In acute
      sarcoidosis, relative proportions of LDL and HDL particles were associated with
      levels of inflammatory markers, whereas in chronic disease an association with
      concentrations of serum lipid parameters was found. CONCLUSIONS: The obtained
      results demonstrate adverse lipoprotein subfraction profile in sarcoidosis with
      sustained alterations during disease course. Evaluation of LDL and HDL particles
      may be helpful in identifying patients with higher cardiovascular risk, at least
      for prolonged corticosteroid therapy due to chronic disease course.

PMID- 24283860
TI  - Unintended reporting of misleading Hb A(1c) values when using assays incapable of
      detecting hemoglobin variants.
AB  - CONTEXT: It is recommended that hemoglobin (Hb) A1c (Hb A1c) not be used to
      assess average glycemia in patients who have altered red blood cell life span.
      OBJECTIVE: To investigate the frequency of reporting an Hb A1c value for Hb
      variant samples that do not include Hb A. DESIGN: Hb A1c samples (n = 500) were
      procured and screened for Hb variants that may affect Hb A1c interpretation (Hb
      SS, Hb SC, and Hb S-beta-thalassemia). Five of each of these samples were tested
      by ion-exchange high-performance liquid chromatography, immunoturbidimetric
      assay, second-generation immunoturbidimetric assay, and affinity chromatography.
      RESULTS: Eleven (2.2%) homozygous Hb SS, 6 (1.2%) Hb SC, and 5 (1.0%) Hb S-beta
      thalassemia samples were identified out of the 500 samples tested. Three of 4
      instruments investigated in this study are known to not be plagued by analytic
      interference from these Hb variants but disturbingly reported Hb A1c values in
      the absence of Hb A. CONCLUSIONS: The improved analytic specificity of Hb A1c
      platforms has by and large eliminated interferences from the most common
      heterozygous Hb variants. A consequence, however, is the potential for unintended
      reporting of Hb A1c results in the presence of homozygous and compound
      heterozygous Hb variants that lack Hb A and the inability to distinguish those
      samples not recommended to be used for patient care. The ability to identify
      samples harboring Hb variants that preclude the utility of Hb A1c may be
      beneficial in high prevalence populations.

PMID- 24283861
TI  - In compressed lung tissue microscopic sections of adenocarcinoma in situ may
      mimic papillary adenocarcinoma.
AB  - CONTEXT: Surgical removal and pathologic handling of lung tissue has a
      compressive effect upon its architecture. The effect of surgical atelectasis on
      morphology has not been examined in depth, especially with respect to lung
      adenocarcinomas. OBJECTIVE: To examine the influence of surgical atelectasis on
      morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern.
      DESIGN: In 2 cases serial sections of resected pulmonary adenocarcinoma were
      used, as was a 3-dimensional reconstruction. Elastin stains were performed on
      primary and metastatic adenocarcinomas. RESULTS: Perfusion fixation of another
      case showed marked morphologic differences of less compressed peripheral lung
      tissue, emphasizing the preexisting alveolar structure. An elastic stain may help
      identify true lesional architecture. CONCLUSIONS: We demonstrate that microscopic
      sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise
      to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate
      appreciation of different tumor architecture in lung adenocarcinoma has important
      biologic and clinical implications. Pathologists should be aware of the
      possibility of misclassification of adenocarcinoma pattern due to tissue
      artifacts caused by lung tissue handling.

PMID- 24283862
TI  - How to evaluate a potential merger or acquisition.
AB  - Economic imperatives in health care financing are compelling a variety of
      mergers, acquisitions, integrations, and other forms of amalgamation. As
      hospitals merge, their pathology practices are merging. Physicians are forming
      clinically integrated groups, both with and without hospitals. Universities,
      commercial laboratories, and even insurance companies are acquiring laboratories
      and pathology practices. There are few standards or guidelines to help the
      practicing pathologist respond to such new undertakings. In the present study, we
      present a "how-to" guide or template to assist pathologists in evaluating
      proposals to amalgamate and in managing the alliance. The procedure begins with
      an articulation of the cons and pros, followed by a series of assessments of the
      cultures, the market, the organization, and operations, as well as a legal and
      financial assessment and human resources appraisal of each of the entities. We
      then outline the method for developing an organizational and operational model
      for the new merged entity and for performing the feasibility analysis, making a
      final decision, drafting a contract, and developing the business plan for the new
      venture. 

PMID- 24283863
TI  - Tumor-to-tumor metastasis with endometrial carcinoma metastatic to squamous cell
      carcinoma of vulva: the first reported case.
AB  - Endometrial carcinoma metastasizing to the vulva is a rare occurrence, with only
      15 reported cases in the literature. To our knowledge, no cases of tumor-to-tumor
      metastasis involving endometrial carcinoma as a donor tumor have ever been
      published. We report the first case of an endometrial carcinoma as a donor tumor
      metastasizing to a squamous cell carcinoma of the vulva, a recipient tumor. A 79
      year-old woman with a history of endometrioid adenocarcinoma of the uterus
      presented with a vulvar lesion. Pathologic examination of the excised lesion
      confirmed the presence of metastatic endometrioid adenocarcinoma; however, it was
      found within a well-differentiated squamous cell carcinoma of the vulva.
      Surrounding the squamous cell carcinoma was a background of a high-grade vulvar
      intraepithelial lesion (vulvar intraepithelial neoplasia 3), and
      immunohistochemistry confirmed the presence of 2 separate tumors involved in a
      tumor-to-tumor metastasis. This unique case highlights the importance of
      awareness of the phenomenon, and expands the current spectrum of tumor-to-tumor
      metastases. 

PMID- 24283864
TI  - Cervical adenocarcinoma identification by testing for chromosomal abnormalities.
AB  - We report on a case of cervical adenocarcinoma in situ in a 42-year-old woman
      with a history of human papillomavirus infection. Repeat cytology, human
      papillomavirus testing, and colposcopy failed to identify the lesion. Testing of
      the cervical cell DNA identified chromosomal abnormalities, prompting a cervical
      cone biopsy, which identified adenocarcinoma in situ. 

PMID- 24283865
TI  - Uterine tumors resembling ovarian sex cord tumors.
AB  - Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms of
      unknown etiology. Only 67 cases have been reported in the literature, to our
      knowledge, so far. The neoplasm usually occurs in middle-aged women. Most
      patients present with abnormal uterine bleeding and/or abdominal pain, along with
      an enlarged uterus or a palpable uterine mass. There is no specific imaging
      finding, and the diagnosis is made exclusively on histopathologic examination. A
      multitude of architectural patterns are described, which include plexiform cords,
      anastomosing trabeculae, watered-silk, microfollicle, macrofollicle, tubules,
      retiform, solid cellular islands, and diffuse pattern of growth. The neoplastic
      cells are usually small with round to ovoid nuclei, nuclear monotony, mild
      nuclear hyperchromasia, and inconspicuous nucleoli with scant eosinophilic
      cytoplasm. Nuclear grooves are rare. Mitotic figures are infrequent, and necrosis
      is mostly absent. This tumor depicts a diverse immunohistochemical profile with
      expression of sex cord, epithelial, and smooth muscle lineages markers. Sex cord
      markers, such as inhibin, calretinin, CD99, WT1, and MART-1; epithelial markers,
      such as pancytokeratin and epithelial membrane antigen; smooth muscle markers,
      such as smooth muscle actin, desmin, and histone deacetylase 8; and miscellaneous
      markers, such as CD10, estrogen receptor, progesterone receptor, S100, and CD117,
      are often coexpressed. Immunoexpression for calretinin and at least for one of
      the other sex cord markers is required to establish a diagnosis of UTROSCT.
      Hysterectomy with or without bilateral salpingo-oophorectomy is usually the
      treatment for UTROSCT. Although most UTROSCTs behave benignly, some do recur, and
      thus, this entity should be considered as a tumor of low malignant potential. In
      this review, we discuss the current knowledge on UTROSCT and its clinical
      relevance. 

PMID- 24283866
TI  - Lymphangioma of the palatine tonsil.
AB  - Lymphangioma of the palatine tonsil is a rare, benign lesion that presents as a
      tonsillar outgrowth and causes symptoms related to irritation and airway
      obstruction. Histologically, the mass has abundant dilated lymphatic channels
      amid a fibrous stroma with lymphoid and adipose elements. There are several
      theories regarding the pathogenesis of these lesions, and the appropriate
      diagnostic classification is controversial. Because a lymphangioma may resemble a
      true neoplasm of the palatine tonsil clinically, the lesion must be removed for
      accurate histologic diagnosis and to rule out malignancy. Lymphangioma of the
      palatine tonsil is treated with surgical excision and has no recurrence once
      completely resected. 

PMID- 24283870
TI  - Optimizing management of ruxolitinib in patients with myelofibrosis: the need for
      individualized dosing.
AB  - Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients
      with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated
      with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly,
      and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib
      reduces splenomegaly and alleviates MF-related symptoms, with concomitant
      improvements in quality of life measures, for the overwhelming majority of
      treated patients. In addition, ruxolitinib provided an overall survival advantage
      as compared with either placebo or what was previously considered best available
      therapy in the two phase III studies. The most common adverse events with
      ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which
      are expected based on its mechanism of action. Experience from the phase III
      studies shows that these hematologic events can be managed effectively with dose
      modifications, temporary treatment interruptions, as well as red blood cell
      transfusions in the case of anemia and, importantly, are rarely cause for
      permanent treatment discontinuation. This review summarizes data supporting
      appropriate individualized patient management through careful monitoring of blood
      counts and dose titration as needed in order to maximize treatment benefit. 

PMID- 24283871
TI  - Exploring and exploiting the aberrant DNA methylation profile of endocrine
      resistant breast cancer.

PMID- 24283872
TI  - 3D genome architecture in the mammalian nucleus.

PMID- 24283873
TI  - Effect of exercise on DNA methylation and metabolism in human adipose tissue and
      skeletal muscle.

PMID- 24283875
TI  - Interview: from Down's syndrome to basic epigenetics and back again.
AB  - Dr Jeanne Lawrence talks to Caroline Telfer, Commissioning Editor. Dr Jeanne
      Lawrence is an internationally recognized leader in the study of chromosome
      regulation by noncoding RNA and nuclear and genome organization. Her research
      bridges fundamental questions about genome regulation with clinical implications
      of recent advances in epigenetics. Her interest in chromosome structure and
      regulation has been a theme throughout her career and she has been honored for
      her work developing sensitive FISH technology for the detection of single copy
      genes, as well as RNAs. Her laboratory's publications include the initial
      demonstration of cell type-specific gene organization with nuclear subdomains;
      the novel biology of a noncoding RNA, XIST, which coats a whole X-chromosome to
      induce its silencing; and a new architectural role for a large noncoding RNA to
      scaffold a nuclear body. Her laboratory's work on epigenetic chromosome
      regulation in stem cells led to recent studies regarding unanticipated roles of
      repeat sequences in normal chromosome regulation and deregulation in cancer. Most
      recently, her laboratory has demonstrated a new approach to translate the basic
      mechanism of X-chromosome inactivation to correct a chromosomal dosage imbalance
      in patient-derived cells with trisomy 21 (Down's syndrome). Dr Lawrence has
      received awards from numerous agencies, including a Research Career Development
      Award from the National Center for Human Genome Research, career awards from the
      American Society of Cell Biology, the German Society for Biochemistry, the
      Muscular Dystrophy Association and a John Merck Fund Translational Research
      Award. She has served on the NIH National Advisory Council for Human Genome
      Research, numerous study sections and is currently a monitoring editor for the
      Journal of Cell Biology. Dr Lawrence has a BA in Biology and Music from Stephens
      College (MO, USA), a MS in Human Genetics and Genetic Counseling from Rutgers
      University (NJ, USA) and a PhD in Developmental Biology from Brown University
      (RI, USA). She is currently a Professor and Interim Chair of the Department of
      Cell and Developmental Biology at the University of Massachusetts Medical School
      (MA, USA). 

PMID- 24283876
TI  - Epigenetic and circulating biomarkers: future analytes for liquid biopsies.

PMID- 24283878
TI  - Quantitative identification of differentially methylated loci based on relative
      entropy for matched case-control data.
AB  - AIM: As an important epigenetic modification, DNA methylation plays a critical
      role in regulating multiple biological processes and diseases. Many efforts have
      been devoted to identifying differentially methylated loci (DML) between cases
      and controls. MATERIALS & METHODS: However, most present methods are statistical
      and are limited in handling methylation data with characteristics of high
      heterogeneity and non-normal distribution. Here, a quantitative method,
      quantitative DML (QDML), based on modified relative entropy is introduced to face
      these challenges, which can identify DML, hypermethylated loci and hypomethylated
      loci simultaneously. QDML, compared with some statistical methods, does not
      require a presupposed distribution of methylation data. Furthermore, QDML is more
      powerful in handling highly heterogeneous data, owing to the difference in
      sensitivity on every matched sample pair in case-control groups rather than the
      overall difference of all samples. RESULTS: Simulation studies and real-data
      application show that QDML has a higher accuracy and a lower false-positive rate
      when identifying DML than statistical methods. CONCLUSION: QDML is developed to
      identify DML based on relative entropy that can quantify the difference in
      methylation status between cases and controls. Its applications are not limited
      to methylation data and can be extended to other case-control studies.

PMID- 24283877
TI  - Placental DNA methylation alterations associated with maternal tobacco smoking at
      the RUNX3 gene are also associated with gestational age.
AB  - AIMS: The developmental origins of health and disease hypothesis states that
      later-life disease may be influenced by the quality of the in utero environment.
      Environmental toxicants can have detrimental effects on fetal development,
      potentially through effects on placental development and function. Maternal
      smoking during pregnancy is associated with low birth weight, preterm birth and
      other complications, and exposure to cigarette smoke in utero has been linked to
      gross pathologic and molecular changes to the placenta, including differential
      DNA methylation in placental tissue. The aim of this study was to investigate the
      relationship between maternal smoking during pregnancy, methylation changes in
      the placenta and gestational age. MATERIALS & METHODS: We used Illumina((r))'s
      (CA, USA) Human Methylation27 BeadChip technology platform to investigate the
      methylation status of 21,551 autosomal, non-SNP-associated CpG loci in DNA
      extracted from 206 human placentas and examined loci whose variation in
      methylation was associated with maternal smoking during pregnancy. RESULTS: We
      found that methylation patterns of a number of loci within the RUNX3 gene were
      significantly associated with smoking during pregnancy, and one of these loci was
      associated with decreased gestational age (p = 0.04). CONCLUSION: Our findings,
      demonstrating maternal smoking-induced changes in DNA methylation at specific
      loci, suggest a mechanism by which in utero tobacco smoke exposure could exert
      its detrimental effects upon the health of the fetus.

PMID- 24283880
TI  - 5-hydroxymethylcytosine profiling as an indicator of cellular state.
AB  - DNA methylation is widely studied in the context of cancer. However, the
      rediscovery of 5-hydroxymethylation of DNA adds a new layer of complexity to
      understanding the epigenetic basis of development and disease, including
      carcinogenesis. There have been significant advances in techniques for the
      detection of 5-hydroxymethylcytosine and, with this, greater insight into the
      distribution, regulation and function of this mark, which are reviewed here.
      Better understanding of the associated pathways involved in regulation of, and
      by, 5-hydroxymethylcytosine may give promise to new therapeutic targets. We
      discuss evidence to support the view of 5-hydroxymethylcytosine as a unique and
      dynamic mark of cellular state. These 5-hydroxymethylcytosine profiles may offer
      optimism for the development of diagnostic, prognostic and predictive biomarkers.

PMID- 24283879
TI  - How has the study of the human placenta aided our understanding of partially
      methylated genes?
AB  - While the human genome sequence is relatively uniform between the cells of an
      individual, the DNA methylation of the genome (methylome) has unique features in
      different cells, tissues and stages of development. Recent genome-wide sequencing
      of the methylome has revealed large partially methylated domains (PMDs) in the
      human placenta. Unlike CpG islands and Polycomb-regulated regions, which can also
      have low levels of methylation, placental PMDs cover approximately 37% of the
      human genome and are associated with inaccessible chromatin and the repression of
      tissue-specific genes. Here, we summarize the interesting biological questions
      that have arisen as a result of finding PMDs in the human placenta, including how
      PMDs form, what they do, how they evolved and how they might be relevant to human
      disease. 

PMID- 24283881
TI  - Modulation of epigenetic regulators and cell fate decisions by miRNAs.
AB  - Mammalian gene expression is controlled at multiple levels by a variety of
      regulators, including chromatin modifiers, transcription factors and miRNAs. The
      latter are small, ncRNAs that inhibit the expression of target mRNAs by reducing
      both their stability and translation rate. In this review, we summarize the
      recent work towards characterizing miRNA targets that are themselves involved in
      the regulation of gene expression at the epigenetic level. Epigenetic regulators
      are strongly enriched among the predicted targets of miRNAs, which may contribute
      to the documented importance of miRNAs for pluripotency, organism development and
      somatic cell reprogramming. 

PMID- 24283883
TI  - Dynamic changes of the epigenetic landscape during cellular differentiation.
AB  - Epigenetic mechanisms are crucial to stabilize cell type-specific gene-expression
      programs. However, during differentiation, these programs need to be modified - a
      complex process that requires dynamic but tightly controlled rearrangements in
      the epigenetic landscape. During recent years, the major epigenetic machineries
      for gene activation and repression have been extensively characterized. Snapshots
      of the epigenetic landscape in pluripotent versus differentiated cells have
      further revealed how chromatin can change during cellular differentiation.
      Although transcription factors are the key drivers of developmental transitions,
      it became clear that their function is greatly influenced by the chromatin
      environment. Better insight into the tight interplay between transcription factor
      networks and the epigenetic landscape is therefore necessary to improve our
      understanding of cellular differentiation mechanisms. These systems can then be
      challenged and modified for the development of regenerative therapies. 

PMID- 24283884
TI  - Epigenetic deregulation of genomic imprinting in humans: causal mechanisms and
      clinical implications.
AB  - Mammalian genes controlled by genomic imprinting play important roles in
      development and diverse postnatal processes. A growing number of congenital
      disorders have been linked to genomic imprinting. Each of these is caused by
      perturbed gene expression at one principal imprinted domain. Some imprinting
      disorders, including the Prader-Willi and Angelman syndromes, are caused almost
      exclusively by genetic mutations. In several others, including the Beckwith
      Wiedemann and Silver-Russell growth syndromes, and transient neonatal diabetes
      mellitus, imprinted expression is perturbed mostly by epigenetic alterations at
      'imprinting control regions' and at other specific regulatory sequences. In a
      minority of these patients, DNA methylation is altered at multiple imprinted
      loci, suggesting that common trans-acting factors are affected. Here, we review
      the epimutations involved in congenital imprinting disorders and the associated
      clinical features. Trans-acting factors known to be causally involved are
      discussed and other trans-acting factors that are potentially implicated are also
      presented. 

PMID- 24283882
TI  - Epigenomics and allergic disease.
AB  - Allergic disease development is affected by both genes and the environment, and
      epigenetic mechanisms are hypothesized to mediate these environmental effects. In
      this article, we discuss the link between the environment, DNA methylation and
      allergic disease, as well as questions of causality inherent to analyses of DNA
      methylation. From the practical side, we describe characteristics of allergic
      phenotypes and contrast different epidemiologic study designs used in epigenetic
      research. We examine methodological considerations, how best to conduct
      preprocessing and analysis of DNA methylation data sets, and the latest methods,
      technologies and discoveries in this rapidly advancing field. DNA methylation and
      other epigenetic marks are firmly entwined with allergic disease, a link that may
      hold the basis for future allergic disease diagnosis and treatment. 

PMID- 24283887
TI  - Fabrication of a sealed electrochemical microcell for in situ soft X-ray
      microspectroscopy and testing with in situ co-polypyrrole composite
      electrodeposition for Pt-free oxygen electrocatalysis.
AB  - In this paper we report on the fabrication and testing of a novel concept of
      sealed electrochemical microcell for in situ soft X-ray microspectroscopy in
      transmission, dedicated for nonvacuum compatible electrolytes. The microcell,
      fabricated using ultraviolet lithography, at variance with previous versions of
      electrochemical wet cells, that featured an optical window glued on top of the
      electrode system and a very limited electrolyte volume, the device presented here
      is a single solid block based around a microfabricated channel with fixed optical
      windows and apt for microfluidic work. Moreover, this cell allows to employ an
      advanced electrodic geometry developed in our group - so far used only in open
      electrochemical cells for work with vacuum-compatible electrolytes - also with
      low-vapor pressure liquids, possibly saturated with the required gases. The cell
      optimal electrode design allows three-electrode electrochemical control typical
      of traditional electrochemical experiments. The first electrochemical experiments
      with this new cell explore the electrochemical growth of a Co-polypyrrole, a
      composite electrocatalyst material with promising performance to replace the
      expensive Pt catalyst in fuel-cell oxygen electrodes. Morphological and chemical
      state distributions of Co codeposited with polypyrrole has been followed as a
      function of time and position, yielding unprecedented information on the
      processes relevant to the synthesis of this catalyst. 

PMID- 24283888
TI  - Fabrication of ultrathin membrane via layer-by-layer self-assembly driven by
      hydrophobic interaction towards high separation performance.
AB  - A novel and facile layer-by-layer (LbL) self-assembly process driven by
      hydrophobic interaction and then reinforced by hydrogen bond was developed to
      prepare ultrathin membranes. Gelatin (GE) and tannic acid (TA) were alternately
      deposited on polyacrylonitrile (PAN) ultrafiltration membranes to obtain GE/TA
      membranes. The required number of deposition cycles for acceptable
      permselectivity of membrane was greatly reduced compared with that of the
      traditional LbL self-assembly process and could be ascribed to the rapid growth
      of membrane thickness and the integrity of the innermost gelatin layer. Higher
      surface hydrophilicity and more appropriate free volume characteristics were
      obtained for GE/TA multilayer membranes compared with pristine gelatin membrane.
      Moreover, the GE/TA multilayer membrane exhibited improved stability even at high
      water content of 30 wt %. The membrane separation experiments with pervaporation
      dehydration of ethanol aqueous solution as a model system demonstrated the GE/TA
      multilayer membrane achieved higher water permselectivity than the pristine
      gelatin membrane. High operation stability was acquired in the long-term membrane
      separation test. 

PMID- 24283885
TI  - Epigenetic effects of green tea polyphenols in cancer.
AB  - Epigenetics describes heritable alterations of gene expression and chromatin
      organization without changes in DNA sequence. Both hypermethylation and
      hypomethylation of DNA can affect gene expression and the multistep process of
      carcinogenesis. Epigenetic changes are reversible and may be targeted by dietary
      interventions. Bioactive compounds from green tea (GT) such as (-)
      epigallocatechin gallate have been shown to alter DNA methyltransferase activity
      in studies of esophageal, oral, skin, Tregs, lung, breast and prostate cancer
      cells, which may contribute to the chemopreventive effect of GT. Three out of
      four mouse model studies have confirmed the inhibitory effect of (-)
      epigallocatechin gallate on DNA methylation. A human study demonstrated that
      decreased methylation of CDX2 and BMP-2 in gastric carcinoma was associated with
      higher GT consumption. It is the goal of this review to summarize our current
      knowledge of the potential of GT to alter epigenetic processes, which may be
      useful in chemoprevention. 

PMID- 24283889
TI  - Running-induced patellofemoral pain fluctuates with changes in patella water
      content.
AB  - Although increased bone water content resulting from repetitive patellofemoral
      joint loading has been suggested to be a possible mechanism underlying
      patellofemoral pain (PFP), there is little data to support this mechanism. The
      purpose of the current study was to determine whether running results in
      increases in patella water content and pain and whether 48 hours of rest reduces
      patella water content and pain to pre-running levels. Ten female runners with a
      diagnosis of PFP (mean age 25.1 years) participated. Patella water content was
      quantified using a chemical-shift-encoded water-fat magnetic resonance imaging
      (MRI) protocol. The visual analog scale (VAS) was used to quantify subjects' pain
      levels. MRI and pain data were obtained prior to running, immediately following a
      40-minute running session, and 48 hours post-running. Pain and patella water
      content were compared among the 3 time points using one-way ANOVA's with repeated
      measures. Immediately post-running, persons with PFP reported significant
      increases in pain and exhibited elevated patella water content. Pain and patella
      water content decreased to pre-running levels following 48 hours of rest. Our
      findings suggest that transient changes in patella water content associated with
      running may, in part, contribute to patellofemoral symptoms.

PMID- 24283890
TI  - Dissolution enhancement of itraconazole by hot-melt extrusion alone and the
      combination of hot-melt extrusion and rapid freezing--effect of formulation and
      processing variables.
AB  - We investigated the effects of the hot-melt extrusion (HME) process on the
      properties of itraconazole (ITZ) amorphous solid dispersions made by thin film
      freezing (TFF) technology. The ITZ-HPMCAS L (1:2) TFF composition exhibited
      limited drug release in acidic media. HME of the ITZ-HPMCAS TFF composition with
      hydrophilic carriers improved the drug release rate in acidic media. The type and
      level of hydrophilic carrier in the composition affected the dissolution profiles
      of the extrudates. A design of experiments (DoE) study was conducted to elucidate
      those effects. Hot-melt extrusion processing variables such as extrusion
      temperature and screw configuration also played a critical role on the properties
      of the extruded compositions. A higher degree of mixing reduced the crystallinity
      of semicrystalline excipients and favored the drug release in the acidic media;
      moreover, the drug precipitation rate in the neutral pH media was reduced. 

PMID- 24283891
TI  - Anesthetic neurotoxicity: what to tell the parents?
AB  - Over the past decade, numerous preclinical and retrospective human studies have
      reported that the provision of anesthetic and sedative agents to infants and
      children may be associated with adverse neurodevelopmental outcomes. These data
      have gained widespread attention from professional and regulatory agencies,
      including the public at large. As such, pediatric anesthesiologists are being
      increasingly questioned by parents about the risks of anesthetic agents on their
      children's neurocognitive development. To impart a framework from which
      anesthesiologists may address the apprehensions of parents who actively bring up
      this issue, we review the data supporting anesthetic neurotoxicity and discuss
      its strengths and limitations. As many parents are not yet aware and do not
      actively raise these concerns, we also discuss whether such a conversation should
      be undertaken as a part of the consent process. 

PMID- 24283892
TI  - Tonsillectomy as a treatment for psoriasis: a review.
AB  - Psoriasis is a chronic skin disorder that affects 1% to 3% of the general
      population worldwide. Streptococcal infection, especially streptococcal
      pharyngitis, has been shown to be a significant trigger of psoriasis in some
      patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to
      the role of the palatine tonsils as an immunological organ that may generate
      autoreactive T cells, tonsillectomy has been investigated as a treatment for
      psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for
      palmoplantar pustulosis, a condition that shares features with pustular
      psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque
      psoriasis and guttate psoriasis. Recently, the first randomized, controlled
      clinical trial of tonsillectomy was performed. Here, we review the available
      evidence for the benefit of tonsillectomy as a treatment for palmoplantar
      pustulosis and psoriasis. We also discuss molecular studies aimed at
      understanding the role of tonsils in skin disease.

PMID- 24283893
TI  - Novel B4GALNT1 mutations in a complicated form of hereditary spastic paraplegia.

PMID- 24283894
TI  - Molecular structural changes of plasticized PVC after UV light exposure.
AB  - Plasticized poly(vinyl chloride) (PVC) materials for industrial, medical, and
      household use are often intentionally exposed to UV light, though its impact on
      the molecular integrity and toxicity of the surface and bulk of PVC materials is
      still not well understood. This paper investigates the surface and bulk molecular
      changes of plasticized PVC films with 25, 10, or 0 wt % bis-2-ethylhexyl
      phthalate (DEHP) plasticizer after exposure to short wave (254 nm) or long wave
      (365 nm) UV light. Surface analytical techniques including sum frequency
      generation vibrational spectroscopy (SFG) revealed short wave UV exposure induced
      major molecular changes on the plasticized PVC surfaces, resulting in increased
      surface hydrophilicity and decreased CH3 content with increasing exposure time.
      Additionally, it was deduced from multiple techniques that the surface and the
      bulk of the plastic exposed to short wave UV contained phthalic monoesters and
      phthalic acid formed from multistep radical reactions. In contrast, when exposed
      to long wave UV, molecular content and ordering on the surfaces of the plastic
      remained relatively unchanged and the introduction of DEHP in plastic helped
      protect PVC chains from degradation. Results from this study demonstrate short
      wave UV exposure will result in plastic surfaces containing phthalates and
      phthalate-related products accessible to contact by living organisms. 

PMID- 24283895
TI  - Antiplasmin, but not amiloride, prevents synovitis and cartilage damage following
      hemarthrosis in hemophilic mice.
AB  - BACKGROUND: Blood-induced joint damage is characterized by synovitis and
      cartilage damage. Recently, we demonstrated that joint bleeding in hemophilic
      mice results in elevated synovial levels of urokinase plasminogen activator (u
      PA) and plasmin, and in plasmin-mediated cartilage damage. OBJECTIVE: To evaluate
      whether treatment with amiloride (an inhibitor of u-PA) or antiplasmin attenuates
      synovitis and cartilage damage following joint bleeding in hemophilic mice.
      METHODS: Following the induction of joint bleeding, hemophilic mice were
      randomized between daily oral treatment with amiloride (1 mg kg-1) or control, or
      weekly intra-articular treatment with amiloride (2.5 mg mL-1), antiplasmin (2.5
      mg mL-1), or control. After 5 weeks of treatment, synovitis and cartilage damage
      were determined on hematoxylin and eosin-stained (Valentino score) and Safranin O
      stained sections, respectively. RESULTS: No effects of oral and intra-articular
      treatment with amiloride were found. In contrast, intra-articular treatment with
      antiplasmin resulted in significant (P < 0.01) reductions in both synovitis
      (score 1, 11.1% vs. 0%; score 2, 11.1% vs. 4.2%; score 3, 61.1% vs. 16.7%; score
      4, 5.6% vs. 29.2%; score 5, 11.1% vs. 20.8%; score 6, 7.7% vs. 8.3%; score 7, 0%
      vs. 8.3%; and score 8, 0% vs. 12.5%) and cartilage damage (score 2, 10% vs. 8.3%;
      score 3, 50% vs. 12.5%; score 4, 30% vs. 33.3%; score 5, 10% vs. 33.3%; and score
      6, 0% vs. 16.7%) as compared with controls. CONCLUSIONS: Intra-articular
      treatment with antiplasmin (but not amiloride) following joint bleeding prevented
      synovitis and cartilage damage in hemophilic mice. These data offer promise for
      the use of antiplasmin as a new therapeutic intervention for patients who suffer
      from joint bleeds despite administration of clotting factor.

PMID- 24283897
TI  - Political clouds over neurology.

PMID- 24283896
TI  - Induction and coverage times for crude oil droplets spreading on air bubbles.
AB  - The interactions between crude oil droplets and air bubbles were studied by the
      droplet-bubble micromanipulator technique. Eight crude oils were investigated,
      and some aspects of the involved mechanisms were discussed. The induction time
      was measured for air bubbles approaching crude oil droplets in different aqueous
      phases. Distinct differences were observed in the presence and absence of salts,
      which showed the importance of long-ranged electrostatic repulsive forces on thin
      film stability. The results also suggested that adsorption of dissolved
      hydrocarbons at air bubble surfaces may increase the potential energy barrier in
      the thin liquid film. Furthermore, the time needed for crude oil droplets to
      spread over the air bubble surfaces (referred to as coverage time) was determined
      for the crude oils. The results showed that the spreading velocity decreased with
      increasing viscosity of the crude oil. The detailed understanding of this type of
      interaction is considered to be a precursor for improving the oil removal
      efficiency during the flotation process. 

PMID- 24283898
TI  - The sun shines on neurology in Europe but for how long?

PMID- 24283900
TI  - A comment on "Neurologic education for the future" by Glick et al (1997).

PMID- 24283899
TI  - Neurologic education for the future: a decade of curricular reform at Harvard
      Medical School.
AB  - The field of neurology is undergoing significant changes to which curricular
      reform is both responding and contributing. We reflect on a decade of experience
      at Harvard Medical School with integration of neuroscience, behaviour,
      pathophysiology and introductory clinical skills. As part of Harvard's "New
      Pathway" curriculum, this coordinated, pre-clerkship program embraces a "hybrid"
      form of problem-based learning. A variety of methods are employed synergistically
      to meet the two broad goals of preparing for competency in neurologic clerkships
      and for career-long learning in clinically relevant neuroscience. We articulate
      specific ways of elevating the level of intellectual inquiry, involving multi
      disciplinary faculty more productively, and vertically integrating the learning
      experience through the years of medical school. 

PMID- 24283901
TI  - Neurological education in Europe: the need for a survey of the current status.

PMID- 24283902
TI  - Continuing medical education in Europe-trends and developments.

PMID- 24283903
TI  - A model of neurological disorder: a basis for logical and structured thinking and
      reasoning in neurology.
AB  - A model of neurological disorder in graphical form, based upon a model proposed
      by the World Health Organisation, is presented. This model is intended to be a
      basis for a logical and structured thinking and reasoning in neurology, not least
      in diagnosis. The model is a chain of basic elements in which each element causes
      the following one. The chain can be divided in two parts. The first part is:
      Etiology -> Pathology -> Manifestation. Pathology is described by the properties
      of the lesion in the nervous system. Manifestation is the symptoms and signs,
      that can be summarised as Semiology, in fact, synonymous with Impairment. The
      second part of the model is then: Manifestation (= Impairment) -> Disability ->
      Handicap. The terms disease and disorder are not contained within the chain of
      basic elements. The manifestation gives the patient an awareness of disorder and
      the condition may be classified as syndrome or disease. Neither the awareness of
      disorder nor the classification influences the chain of basic elements. 

PMID- 24283904
TI  - The neurological examination in the assessment of polyneuropathy in mechanically
      ventilated patients.
AB  - Polyneuropathy has been implicated in critical illness as a cause of difficult
      weaning from artificial ventilation and of rehabilitation problems. We wanted to
      see which clinical parameters can be used to identify patients with
      polyneuropathy in the intensive care. In a prospective study during 18 months,
      mechanically ventilated patients underwent serial neurological and EMG
      investigations in the general intensive care unit of a large community hospital.
      Fifty patients under 75 years old were studied who were on the respirator for
      more than 7 days. Using simple criteria, both a provisional clinical and an EMG
      diagnosis were made with regard to polyneuropathy during the second and fourth
      week and the second month of mechanical ventilation. After the intensive care
      period, 34 surviving patients were also given a final clinical diagnosis which
      was compared to earlier EMG conclusions. Even with crude criteria, such as the
      presence of either paresis or areflexia, maximal sensitivity of the provisional
      clinical judgement was only 60% as compared to concurrent EMG diagnosed
      polyneuropathy. EMG investigations in the intensive care, however, did not
      identify two out of 10 patients with a final clinical diagnosis of
      polyneuropathy. Thus, neurological examination is an insufficient screening
      method for polyneuropathy in intensive care. EMG has a fair diagnostic yield but
      one should realize that it is not an infallible gold standard. 

PMID- 24283905
TI  - Titin antibody positive myasthenia gravis patients have a cellular immune
      response against the main immunogenic region of titin.
AB  - Some myasthenia gravis (MG) patients have antibodies against non-acetylcholine
      receptor (AChR) epitopes of skeletal muscle including titin. Peripheral blood
      lymphocytes from 11 MG patients and 13 blood-donors were tested for lymphocyte
      proliferation after stimulation with the titin peptide MGT-30, which represents
      the main immunogenic region. Four out of seven titin antibody positive patients
      had significant stimulation defined as a stimulation index (SI) above 2. Neither
      of the four titin antibody negative patients nor the 13 blood-donors had SI above
      2 (p = 0.001). Mean SI was significantly higher for T-cells from titin antibody
      positive MG patients, SI = 2.2 +/- 0.8, compared to titin antibody negative
      patients, SI = 0.9 +/- 0.2 (p = 0.01), and blood-donors, SI = 0.8 +/-0.3 (p >
      0.0005). After MGT-30 stimulation, IL-4 was detected in the blood lymphocyte
      culture supernatant from four of the five MG patients examined, but from none of
      the eight blood-donors. Thus, MG patients with anti-titin antibodies have a T
      cell mediated immune reaction against titin. 

PMID- 24283906
TI  - Detection of deletions within the dystrophin gene in Polish families affected
      with Duchenne/Becker muscular dystrophy.
AB  - DNA analysis was performed in 190 cases of Duchenne and Becker muscular
      dystrophies (DMD/BMD), including 150 cases with DMD and 40 cases with BMD, using
      Southern blotting and PCR multiplex techniques with application of 25 pairs of
      primers. Deletions in the overall material were found in 109 cases: 81 (54%) in
      patients with DMD and 28 (70%) in patients with BMD. All the deletions in DMD
      were out of frame with the exception of two cases, whereas in BMD all the
      deletions but two were in frame. Junction fragments were detected in 12 cases of
      DMD. In five cases duplications were found: four in patients with DMD and one in
      a patient with BMD. 

PMID- 24283907
TI  - A prospective radiologic and neurologic follow-up study of 61 HIV-1 -infected
      subjects: early beginning and slow progression of brain atrophy.
AB  - The course of the organic brain disease caused by human immunodeficency virus
      (HIV-1) was evaluated in a follow-up study. The primary material included 200
      consecutive HIV-1 infected persons. Sixty-one subjects, in whom other brain
      affecting factors were excluded, consented to the follow-up. They underwent 278
      radiologic examinations: computed tomography, magnetic resonance imaging, or a
      combination of both (mean 4.6 examinations/subject). Clinical neurologic status
      and, in 40 subjects, cognitive performance were repeatedly evaluated. Sixteen
      subjects were followed up until death and 11 of them were autopsied. Median
      follow-up time was 27 mo (range 2.5-66 mo). The most common radiologic finding
      was atrophy, found in 19 subjects at study entry and developing in 10 subjects
      during the study. Twenty-four subjects (39%) showed the development and/or
      progression of atrophy. Atrophic changes progressed most rapidly in acquired
      immunodeficiency syndrome (AIDS), but mild developing/progressive atrophy was
      found even in 33% of asymptomatic or neurologically intact subjects. Cognitive
      and radiologic worsening were simultaneous in 6/7 subjects with declining
      neuropsychologic test performance. Signal intensity changes including HIV-1
      leukoencephalopathy appeared in AIDS patients with clear cognitive decline. 

PMID- 24283908
TI  - Event-related brain potentials show changed attentional mechanisms in Gilles de
      la Tourette Syndrome.
AB  - In many patients the Gilles de la Tourette Syndrome (TS) is associated with the
      childhood Attention Deficit Hyperactivity Disorder. To gain a general view of
      attentional processes in TS we recorded event-related brain potentials (ERPs) in
      12 TS patients and in a matched control group. Four visual attention experiments
      with different levels of complexity were done (oddball task, pop-out experiment,
      figure extraction and figure conjunction task). The reaction times did not differ
      significantly between groups. The Tourette patients' event-related brain
      potentials showed an increased amplitude of the N2 component to targets in the
      simple oddball and pop-out experiments. While both groups had similar P3b
      latencies to targets in the figure extraction experiment, Tourette patients
      responded less accurately in the most complex figure conjunction task and had
      increased P3b latencies. This is interpreted as evidence for a stronger
      attentional effort of the Tourette patients to obtain behavioural results similar
      to control subjects in easy attentional tasks. Consequently, Tourette patients
      show a reduced performance in complex attentional tasks. 

PMID- 24283909
TI  - Fulminant inflammatory demyelination: long-term course and magnetic resonance
      imaging findings.
AB  - The course and prognosis of adult patients who recover from acute and extensive
      inflammatory demyelination, variously termed fulminant or Marburg's type of
      multiple sclerosis (MS), is poorly known. We report long-term magnetic resonance
      imaging (MRI) and neuropsychological findings in two patients who developed acute
      psychosis and a state resembling akinetic mutism, with CT scan evidence of
      extensive cerebral white matter damage. Both patients ultimately recovered, but
      were left with a severe, non-progressive dementia with prominent frontal lobe
      signs unassociated with motor impairment. Extensive residual MRI lesions with
      evidence of tissue destruction in the white matter and callosal atrophy were
      visible many years after the initial event One of the patients developed a single
      relapsing-remitting episode with multifocal neurological deficits several years
      after the onset, whereas the condition remained monophasic in the other patient
      during an 8 year follow-up. Our observations suggest that while patients with so
      called "fulminant" demyelinating disorders may nowadays survive with supportive
      measures, the disorder may remain stabilized for many years following disease
      onset. 

PMID- 24283910
TI  - Neuropsychological functions in systemic lupus erythematosus: a comparison with
      chronic whiplash patients.
AB  - A comprehensive battery of neuropsychological tests sampling a wide range of
      cognitive functions was administrated to 36 patients with systemic lupus
      erythematosus (SLE), and a control group consisting of 31 patients with
      persistent symptoms after whiplash injury. Our results demonstrated significant
      group differences and suggest that cognitive dysfunction is common in SLE and
      that there are significant abnormalities in the SLE group compared to chronic
      illness of non-immunological nature. Considerable variability occurred in the
      neuropsychological profiles for SLE patients. No significant association was
      found between cognitive dysfunction and use of corticosteroids, except for the
      two neuropsychological tests Digit span and Seashore rhythm test. Associations
      were not found between cognitive dysfunction and depression either, except for
      the Seashore rhythm test. These findings indicate that cognitive dysfunction in
      SLE reflects CNS involvement, rather than coexisting emotional disturbance. No
      significant cognitive impairment was found in the whiplash group. However, our
      results indicate depressed mood among the whiplash group. 

PMID- 24283911
TI  - Patients with heart attacks are not valid models for medial temporal lobe
      amnesia. A neuropsychological and FDG-PET study with consequences for memory
      research.
AB  - Equating the condition after cardiac arrest with that of medial temporal damage,
      and consequently medial temporal lobe amnesia, is questioned on the basis of
      results from a patient who was studied neuropsychologically as well as with
      static and dynamic imaging methods (MRI, PET) 6-9 months after a heart attack.
      The patient manifested severe and persistent anterograde and retrograde amnesia,
      as well as further cognitive deteriorations. While MRI only indicated non
      specific cortical atrophy, PET revealed a severe bilateral affection of the
      thalamus and of both medial and lateral temporal cortices as well as occipito
      parietal hypometabolism. The neuropsychological status indicates that patients
      with a diagnosis of cardiac arrest may suffer very severe and persistent
      cognitive deficits; the imaging analyses show that cardiac arrests may lead to
      quite severe and widespread brain damage which, however, may not be visible with
      current magnetic resonance imaging technology, but which is clearly apparent from
      positron emission tomography. These data suggest that patients with a condition
      after a heart attack may not be valid models for pure hippocampal-or even medial
      temporal lobe-pathology, as they may suffer much more widespread brain damage. 

PMID- 24283912
TI  - A methylenetetrahydrofolate reductase gene polymorphism in multiple sclerosis.
AB  - There have been several indications that cellular methylation pathways might be
      affected in multiple sclerosis (MS). We have investigated 150 MS patients for a
      biallelic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene,
      since the less frequent of these alleles is functionally relevant and is
      associated with reduced enzymatic function. However, the distribution of alleles
      and genotypes was found to be close to identical in MS patients and healthy
      controls, regardless of subgroup analysis after clinical form or HLA class II
      phenotype. We conclude that this polymorphism does not influence susceptibility
      to MS. 

PMID- 24283913
TI  - Infectious meningitis with atypical cerebrospinal fluid cells.
AB  - Cytologic evaluation of the CSF is often difficult when trying to distinguish
      between truly neoplastic and reactive cells. Several non-neoplastic conditions
      may be associated with atypical cells in the CSF, a fact the clinician has to
      consider to avoid inadequate aggressive theraphies. We report here three patients
      with infectious meningitis (due to Herpes zoster virus in two, and
      neuroborreliosis in one) and cytologically atypical cerebrospinal fluid
      lymphocytes. Further characterization showed that the pleocyrosis in these
      patients was of reactive origin. Cytomorphology is frequently insufficient and
      histochemical, immuncytochemical and cellular genome analysis techniques may help
      differentiate atypical reactive cells from neoplastic cells. 

PMID- 24283914
TI  - Progressive expansion of the myotonic dystrophy CTG repeat in asymptomatic
      individuals in three successive generations of a family.
AB  - We report a family in which expansion of CTG repeats was detected in asymptomatic
      carriers of the myotonic dystrophy allele in three successive generations. PCR
      based analysis of the expanded CTG repeat revealed intergenerational
      amplification of the mutation. We show here that the myotonic dystrophy mutation
      may remain clinically silent, not only in the oldest generation of a family, but
      even among siblings and offspring of symptomatic cases. This may represent a
      mechanism for the maintenance of the myotonic dystrophy gene in the population. 

PMID- 24283915
TI  - Migraine associated with head trauma: revision of International Headache
      Society's criteria for posttraumatic headache? A reply to D.C. Haas; AUTHORS
      RESPONSE.

PMID- 24283916
TI  - A comment on "Migraine associated with head trauma" by Russell and Olesen (1996);
      TO THE EDITOR.

PMID- 24283917
TI  - Leukopenia induced by intravenous immune globulin; TO THE EDITOR.

PMID- 24283918
TI  - Is cardiovascular dysregulation in idiopathic Parkinson's syndrome correlated
      with decreased hormonal release?; TO THE EDITOR.

PMID- 24283919
TI  - Expression of basic fibroblastic growth factor, syndecan 1 and tumour necrosis
      factor alpha in resected acute colonic diverticulitis.
AB  - AIM: Inflammation and fibrosis are present in both colonic diverticulitis and
      Crohn's disease (CD). The molecular pattern of basic fibroblastic growth factor
      (bFGF) and syndecan 1 (SD1) expression is altered in stenosing CD, but their
      expression in resected complicated colonic diverticulitis (ACD) is unknown.
      METHOD: The expression of bFGF, SD1 and tumour necrosis factor alpha (TNF-alpha)
      in 20 patients after resection of ACD was compared with 15 patients having a
      resection for CD. Analysis was conducted using real-time reverse transcriptase
      polymerase chain reaction in biopsy samples. RESULTS: Lymphocytic and neutrophil
      inflammation scores were similar in both groups (P = 0.771 and P = 0.562). TNF
      alpha and bFGF expression was significantly higher in ACD than in CD (P < 0.0001
      and P = 0.009). SD1 expression was similar in both groups (P = 0.841).
      CONCLUSION: TNF-alpha and bFGF are significantly overexpressed in ACD with
      respect to CD, whilst SD1 levels do not differ. The findings confirm that
      inflammation and its association with altered molecular patterns of mucosal
      healing may play an important role in the phenotype of the diseases.

PMID- 24283920
TI  - beta-Cell dysfunction is associated with metabolic syndrome severity in adults.
AB  - BACKGROUND: Metabolic syndrome is prevalent in adults characterized by increased
      visceral adiposity and insulin resistance (IR). However, the link between
      pancreatic beta-cell function and metabolic syndrome severity in adults across
      the glucose spectrum is unknown. We hypothesized that poor beta-cell function
      would independently predict a higher metabolic syndrome Z-score (i.e., severity).
      METHODS: Seventy (12 normal glucose tolerant, 37 prediabetic, 21 type 2 diabetic)
      obese adults [62.4+/-1.1 year; 34.6+/-0.6 kg/m(2); data are mean+/-standard error
      of the mean (SEM)] participated in this cross-sectional study. A 2-hr 75-gram
      oral glucose tolerance test (OGTT) was administered, and insulin and glucose area
      under the curve was determined for calculations of insulin action. Fasting and
      glucose-stimulated insulin secretion was calculated using homeostasis model
      assessment of insulin secretion (HOMA-B) and the insulinogenic index (i.e., I(0
      30)/Glc(0-30) or I(60-120)/Glc(60-120)), respectively. Fasting and postprandial
      insulin sensitivity was assessed by HOMA-IR and the Matsuda Index, respectively.
      beta-cell function was estimated using the disposition index via HOMA-B/HOMA-IR,
      I(0-30)/Glc(0-30) or I(60-120)/Glc(60-120) * Matsuda Index, which represents
      basal, first-, and second-phase insulin release, respectively. Body composition
      (via computerized tomography and dual X-ray absorptiometry) and sex-specific
      metabolic syndrome Z-scores were calculated from waist circumference, blood
      pressure, fasting glucose, triglycerides, and high-density lipoproteins. RESULTS:
      Compared to those with normal glucose tolerance, visceral fat and IR were higher
      and beta-cell function was lower in adults with glucose intolerance and type 2
      diabetes mellitus. Elevated visceral fat and IR (HOMA-IR and Matsuda Index)
      correlated with elevated Z-scores (r=0.51, r=0.54, r=-0.49; all P<0.002,
      respectively). Basal, first-, and second-phase beta-cell function correlated with
      low Z-scores (r=-0.59, r=-0.51, and r=-0.43, all P<0.001). Insulin secretion
      significantly predicted the Z-score independent of sex, body fat, blood lipids,
      blood pressure, IR, and glucose metabolism (P<0.005). CONCLUSION: beta-cell
      dysfunction is highly correlated with the severity of metabolic syndrome in
      adults. Future work is warranted to elucidate the mechanism by which
      cardiometabolic disturbances influence insulin secretion.

PMID- 24283921
TI  - Interactions between carbon sequestration and shade tree diversity in a
      smallholder coffee cooperative in El Salvador.
AB  - Agroforestry systems have substantial potential to conserve native biodiversity
      and provide ecosystem services. In particular, agroforestry systems have the
      potential to conserve native tree diversity and sequester carbon for climate
      change mitigation. However, little research has been conducted on the temporal
      stability of species diversity and aboveground carbon stocks in these systems or
      the relation between species diversity and aboveground carbon sequestration. We
      measured changes in shade-tree diversity and shade-tree carbon stocks in 14 plots
      of a 35-ha coffee cooperative over 9 years and analyzed relations between species
      diversity and carbon sequestration. Carbon sequestration was positively
      correlated with initial species richness of shade trees. Species diversity of
      shade trees did not change significantly over the study period, but carbon stocks
      increased due to tree growth. Our results show a potential for carbon
      sequestration and long-term biodiversity conservation in smallholder coffee
      agroforestry systems and illustrate the opportunity for synergies between
      biodiversity conservation and climate change mitigation.

PMID- 24283922
TI  - A phylogenetic framework for evolutionary study of the nightshades (Solanaceae):
      a dated 1000-tip tree.
AB  - BACKGROUND: The Solanaceae is a plant family of great economic importance.
      Despite a wealth of phylogenetic work on individual clades and a deep knowledge
      of particular cultivated species such as tomato and potato, a robust evolutionary
      framework with a dated molecular phylogeny for the family is still lacking. Here
      we investigate molecular divergence times for Solanaceae using a densely-sampled
      species-level phylogeny. We also review the fossil record of the family to derive
      robust calibration points, and estimate a chronogram using an uncorrelated
      relaxed molecular clock. RESULTS: Our densely-sampled phylogeny shows strong
      support for all previously identified clades of Solanaceae and strongly supported
      relationships between the major clades, particularly within Solanum. The Tomato
      clade is shown to be sister to section Petota, and the Regmandra clade is the
      first branching member of the Potato clade. The minimum age estimates for major
      splits within the family provided here correspond well with results from previous
      studies, indicating splits between tomato and potato around 8 Million years ago
      (Ma) with a 95% highest posterior density (HPD) 7-10 Ma, Solanum and Capsicum c.
      19 Ma (95% HPD 17-21), and Solanum and Nicotiana c. 24 Ma (95% HPD 23-26).
      CONCLUSIONS: Our large time-calibrated phylogeny provides a significant step
      towards completing a fully sampled species-level phylogeny for Solanaceae, and
      provides age estimates for the whole family. The chronogram now includes 40% of
      known species and all but two monotypic genera, and is one of the best sampled
      angiosperm family phylogenies both in terms of taxon sampling and resolution
      published thus far. The increased resolution in the chronogram combined with the
      large increase in species sampling will provide much needed data for the
      examination of many biological questions using Solanaceae as a model system.

PMID- 24283923
TI  - Structural insights into DNA replication without hydrogen bonds.
AB  - The genetic alphabet is composed of two base pairs, and the development of a
      third, unnatural base pair would increase the genetic and chemical potential of
      DNA. d5SICS-dNaM is one of the most efficiently replicated unnatural base pairs
      identified to date, but its pairing is mediated by only hydrophobic and packing
      forces, and in free duplex DNA it forms a cross-strand intercalated structure
      that makes its efficient replication difficult to understand. Recent studies of
      the KlenTaq DNA polymerase revealed that the insertion of d5SICSTP opposite dNaM
      proceeds via a mutually induced-fit mechanism, where the presence of the
      triphosphate induces the polymerase to form the catalytically competent closed
      structure, which in turn induces the pairing nucleotides of the developing
      unnatural base pair to adopt a planar Watson-Crick-like structure. To understand
      the remaining steps of replication, we now report the characterization of the
      prechemistry complexes corresponding to the insertion of dNaMTP opposite d5SICS,
      as well as multiple postchemistry complexes in which the already formed unnatural
      base pair is positioned at the postinsertion site. Unlike with the insertion of
      d5SICSTP opposite dNaM, addition of dNaMTP does not fully induce the formation of
      the catalytically competent closed state. The data also reveal that once
      synthesized and translocated to the postinsertion position, the unnatural
      nucleobases again intercalate. Two modes of intercalation are observed, depending
      on the nature of the flanking nucleotides, and are each stabilized by different
      interactions with the polymerase, and each appear to reduce the affinity with
      which the next correct triphosphate binds. Thus, continued primer extension is
      limited by deintercalation and rearrangements with the polymerase active site
      that are required to populate the catalytically active, triphosphate bound
      conformation. 

PMID- 24283924
TI  - Structure-activity relationships of synthetic cordycepin analogues as
      experimental therapeutics for African trypanosomiasis.
AB  - Novel methods for treatment of African trypanosomiasis, caused by infection with
      Trypanosoma brucei are needed. Cordycepin (3'-deoxyadenosine, 1a) is a powerful
      trypanocidal compound in vitro but is ineffective in vivo because of rapid
      metabolic degradation by adenosine deaminase (ADA). We elucidated the structural
      moieties of cordycepin required for trypanocidal activity and designed analogues
      that retained trypanotoxicity while gaining resistance to ADA-mediated
      metabolism. 2-Fluorocordycepin (2-fluoro-3'-deoxyadenosine, 1b) was identified as
      a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei
      infection in mice. Compound 1b is transported through the high affinity TbAT1/P2
      adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has
      good preclinical properties suitable for an oral drug, albeit a relatively short
      plasma half-life. We present a rapid and efficient synthesis of 2-halogenated
      cordycepins, also useful synthons for the development of additional novel C2
      substituted 3'-deoxyadenosine analogues to be evaluated in development of
      experimental therapeutics.

PMID- 24283925
TI  - How to manage intravenous vinflunine in cancer patients with renal impairment:
      results of a pharmacokinetic and tolerability phase I study.
AB  - AIMS: Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is
      registered for the treatment of patients with advanced or metastatic urothelial
      transitional cell carcinoma. This phase I study assessed the effect of renal
      impairment on the pharmacokinetics and tolerability of VFL. METHODS: VFL was
      infused in patients with advanced/metastatic solid tumours once every 3 weeks
      with anticipated dose reduction on the first cycle stratified according to the
      creatinine clearance (CLcr ) values. Pharmacokinetic data were collected on the
      first two cycles in renally impaired patients (CLcr <= 60 ml min(-1) ) and were
      compared with a control cohort of patients (CLcr > 60 ml min(-1) ). RESULTS:
      Thirty-three patients (46-86 years) were treated, 13 in group 1 (40 ml min(-1) <=
      CLcr <= 60 ml min(-1) ) and 20 in group 2 (20 ml min(-1) <= CLcr < 40 ml min(-1)
      ). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group
      1 and 28% in group 2, compared with the control group. The anticipated dose
      reduction given in renally impaired patients (i.e. 280 mg m(-2) and 250 mg m(-2)
      in groups 1 and 2, respectively) yielded similar drug exposure to control
      patients. The tolerance profile of VFL in patients with renal dysfunction was
      similar to that observed in patients with CLcr > 60 ml min(-1) . CONCLUSION: In
      conclusion, the recommended doses of intravenous VFL administered once every 3
      weeks in cancer patients with renal impairment are 280 mg m(-2) when CLcr is
      between 40 and 60 ml min(-1) and 250 mg m(-2) when CLcr is between 20 and <40 ml
      min(-1) .

PMID- 24283926
TI  - XUV-exposed, non-hydrostatic hydrogen-rich upper atmospheres of terrestrial
      planets. Part II: hydrogen coronae and ion escape.
AB  - We studied the interactions between the stellar wind plasma flow of a typical M
      star, such as GJ 436, and the hydrogen-rich upper atmosphere of an Earth-like
      planet and a "super-Earth" with a radius of 2 R(Earth) and a mass of 10 M(Earth),
      located within the habitable zone at ~0.24 AU. We investigated the formation of
      extended atomic hydrogen coronae under the influences of the stellar XUV flux
      (soft X-rays and EUV), stellar wind density and velocity, shape of a planetary
      obstacle (e.g., magnetosphere, ionopause), and the loss of planetary pickup ions
      on the evolution of hydrogen-dominated upper atmospheres. Stellar XUV fluxes that
      are 1, 10, 50, and 100 times higher compared to that of the present-day Sun were
      considered, and the formation of high-energy neutral hydrogen clouds around the
      planets due to the charge-exchange reaction under various stellar conditions was
      modeled. Charge-exchange between stellar wind protons with planetary hydrogen
      atoms, and photoionization, lead to the production of initially cold ions of
      planetary origin. We found that the ion production rates for the studied planets
      can vary over a wide range, from ~1.0*1025 s-1 to ~5.3*1030 s-1, depending on the
      stellar wind conditions and the assumed XUV exposure of the upper atmosphere. Our
      findings indicate that most likely the majority of these planetary ions are
      picked up by the stellar wind and lost from the planet. Finally, we estimated the
      long-time nonthermal ion pickup escape for the studied planets and compared them
      with the thermal escape. According to our estimates, nonthermal escape of picked
      up ionized hydrogen atoms over a planet's lifetime within the habitable zone of
      an M dwarf varies between ~0.4 Earth ocean equivalent amounts of hydrogen (EO(H))
      to <3 EO(H) and usually is several times smaller in comparison to the thermal
      atmospheric escape rates.

PMID- 24283927
TI  - Natural fumarolic alteration of fluorapatite, olivine, and basaltic glass, and
      implications for habitable environments on Mars.
AB  - Fumaroles represent a very important potential habitat on Mars because they
      contain water and nutrients. Global deposition of volcanic sulfate aerosols may
      also have been an important soil-forming process affecting large areas of Mars.
      Here we identify alteration from the Senator fumarole, northwest Nevada, USA, and
      in low-temperature environments near the fumarole to help interpret fumarolic and
      acid vapor alteration of rocks and soils on Mars. We analyzed soil samples and
      fluorapatite, olivine, and basaltic glass placed at and near the fumarole in in
      situ mineral alteration experiments designed to measure weathering under natural
      field conditions. Using synchrotron X-ray diffraction, we clearly observe
      hydroxyl-carbonate-bearing fluorapatite as a fumarolic alteration product of the
      original material, fluorapatite. The composition of apatites as well as secondary
      phosphates has been previously used to infer magmatic conditions as well as
      fumarolic conditions on Mars. To our knowledge, the observations reported here
      represent the first documented instance of formation of hydroxyl-carbonate
      bearing apatite from fluorapatite in a field experiment. Retreat of olivine
      surfaces, as well as abundant NH4-containing minerals, was also characteristic of
      fumarolic alteration. In contrast, alteration in the nearby low-temperature
      environment resulted in formation of large pits on olivine surfaces, which were
      clearly distinguishable from the fumarolic alteration. Raman signatures of some
      fumarolically impacted surfaces are consistent with detection of the biological
      molecules chlorophyll and scytenomin, potentially useful biosignatures.
      Observations of altered minerals on Mars may therefore help identify the
      environment of formation and understand the aqueous history and potential
      habitability of that planet.

PMID- 24283928
TI  - Identification of carotenoids in ancient salt from Death Valley, Saline Valley,
      and Searles Lake, California, using laser Raman spectroscopy.
AB  - Carotenoids are common components of many photosynthetic organisms and are well
      known from the red waters of hypersaline ecosystems where they are produced by
      halophilic algae and prokaryotes. They are also of great interest as biomarkers
      in extraterrestrial samples. Few laser Raman spectroscopy studies have examined
      ancient field samples, where pigments and microscopic life are less defined.
      Here, we have identified carotenoids in ancient halite brine inclusions, 9 ka to
      1.44 Ma in age, from borehole cores taken from Death Valley, Saline Valley, and
      Searles Lake, California, for the first time with laser Raman spectroscopy.
      Carotenoids occurred in fluid inclusions as colorless to red-brown amorphous and
      crystalline masses associated with spheroidal algal cells similar in appearance
      to the common halophilic alga Dunaliella. Spectra from carotenoid standards,
      including beta-carotene, lycopene, and lutein, were compared to microscopically
      targeted carotenoids in fluid inclusions. Carotenoids produced characteristic
      bands in the Raman spectrum, 1000-1020 cm-1 (v3), 1150-1170 cm-1 (v2), and 1500
      1550 cm-1 (v1), when exposed to visible laser excitation. Laser Raman analyses
      confirmed the presence of carotenoids with these characteristic peaks in ancient
      halite. A number of band sets were repeated at various depths (ages), which
      suggests the stability of this class of organic molecules. Carotenoids appear
      well preserved in ancient salt, which supports other observations, for example,
      preserved DNA and live cells, that fluid inclusions in buried halite deposits
      preserve intact halophilic microbial ecosystems. This work demonstrates the value
      of laser Raman spectroscopy and carotenoids in extraterrestrial exploration for
      remnants of microbial life.

PMID- 24283929
TI  - Effects of microgravity on the virulence of Listeria monocytogenes, Enterococcus
      faecalis, Candida albicans, and methicillin-resistant Staphylococcus aureus.
AB  - To evaluate effects of microgravity on virulence, we studied the ability of four
      common clinical pathogens--Listeria monocytogenes, methicillin-resistant
      Staphylococcus aureus (MRSA), Enterococcus faecalis, and Candida albicans--to
      kill wild type Caenorhabditis elegans (C. elegans) nematodes at the larval and
      adult stages. Simultaneous studies were performed utilizing spaceflight,
      clinorotation in a 2-D clinorotation device, and static ground controls. The
      feeding rate of worms for killed E. coli was unaffected by spaceflight or
      clinorotation. Nematodes, microbes, and growth media were separated until exposed
      to true or modeled microgravity, then mixed and grown for 48 h. Experiments were
      terminated by paraformaldehyde fixation, and optical density measurements were
      used to assay residual microorganisms. Spaceflight was associated with reduced
      virulence for Listeria, Enterococcus, MRSA, and Candida for both larval and adult
      C. elegans. These are the first data acquired with a direct in vivo assay system
      in space to demonstrate virulence. Clinorotation reproduced the effects of
      spaceflight in some, but not all, virulence assays: Candida and Enterococcus were
      less virulent for larval worms but not adult worms, whereas virulence of MRSA and
      Listeria were unaffected by clinorotation in tests with both adult and larval
      worms. We conclude that four common clinical microorganisms are all less virulent
      in space.

PMID- 24283930
TI  - Rho kinase inhibitors: a patent review (2012 - 2013).
AB  - INTRODUCTION: The Rho kinase/ROCK is critical in vital signal transduction
      pathways central to many essential cellular activities. Since ROCK possess
      multiple substrates, modulation of ROCK activity is useful for treatment of many
      diseases. AREAS COVERED: Significant progress has been made in the development of
      ROCK inhibitors over the past two years (Jan 2012 to Aug 2013). Patent search in
      this review was based on FPO IP Research and Communities and Espacenet Patent
      Search. In this review, patent applications will be classified into four groups
      for discussions. The grouping is mainly based on structures or scaffolds (groups
      1 and 2) and biological functions of ROCK inhibitors (groups 3 and 4). These four
      groups are i) ROCK inhibitors based on classical structural elements for ROCK
      inhibition; ii) ROCK inhibitors based on new scaffolds; iii) bis-functional ROCK
      inhibitors; and iv) novel applications of ROCK inhibitors. EXPERT OPINION:
      Although currently only one ROCK inhibitor (fasudil) is used as a drug, more
      drugs based on ROCK inhibition are expected to be advanced into market in the
      near future. Several directions should be considered for future development of
      ROCK inhibitors, such as soft ROCK inhibitors, bis-functional ROCK inhibitors,
      ROCK2 isoform-selective inhibitors, and ROCK inhibitors as antiproliferation
      agents.

PMID- 24283931
TI  - Cardiometabolic profile, clinical features, quality of life and treatment
      outcomes in patients with moderate-to-severe psoriasis and psoriatic arthritis.
AB  - Cardiometabolic, clinical and quality-of-life (QoL) measures were assessed before
      and after etanercept treatment in patients who had moderate-to-severe plaque
      psoriasis with and without psoriatic arthritis (PsA) in the PRISTINE trial. Adult
      patients were randomized to receive etanercept 50 mg once weekly or twice weekly
      double-blind for 12 weeks; all patients subsequently received etanercept 50 mg
      once weekly open-label through week 24. Metabolic syndrome was identified in 44
      and 41% of patients with and without PsA, elevated blood pressure in 73 and 56%
      (p<0.05) and diabetes in 21 and 9% (p<0.01), respectively. Significant
      improvements from baseline in Psoriasis Area Severity Index were observed with
      etanercept therapy at all time points over 24 weeks (p<0.001) independent of PsA
      history. At baseline, patients with PsA had worse QoL than patients without PsA.
      After 24 weeks of etanercept, both groups had significant improvement from
      baseline in QoL, but the PsA group had greater improvement than that without PsA.
      Cardiovascular comorbidities were common in psoriasis patients with and without
      PsA, suggesting that clinicians need to be attentive to cardiometabolic
      parameters in this population. Worse QoL was demonstrated in PsA versus psoriasis
      alone. Regardless of patients' PsA status, treatment with etanercept
      significantly improved skin symptoms and QoL measures.

PMID- 24283932
TI  - Movement time to edge and non-edge targets.
AB  - Time to capture a target at the edge of a screen is expected to be less than when
      the target is slightly away from the screen edge. This is due to the effective
      target width, in the direction of cursor movement, being large when the target is
      at the screen edge, allowing a user to control the movement only in a direction
      perpendicular to the direction of movement. An experiment with 71 participants
      and a range of Fitts' Index of Difficulty (ID) showed a strong difference in the
      capture times of targets at the screen edge and targets placed one pixel from the
      screen edge. This advantage is typically 100 ms, independent of the ID of the
      movement. Practitioner Summary: Movement time to icons placed at the screen edge
      (no space between icon and screen edge) is faster than when they are placed a
      short distance from the edge (as in Microsoft Windows).

PMID- 24283933
TI  - The allele 4 of neck region liver-lymph node-specific ICAM-3-grabbing integrin
      variant is associated with spontaneous clearance of hepatitis C virus and
      decrease of viral loads.
AB  - L-SIGN is a C-type lectin expressed on liver sinusoidal endothelial cells
      involved in the capture of hepatitis C virus and trans-infection of adjacent
      hepatocyte cells. The neck region of L-SIGN is highly polymorphic, with three to
      nine tandem repeats of 23 residues. This polymorphism is associated with a number
      of infectious diseases, but has not been explored in HCV. We therefore
      investigated the impact of L-SIGN neck region length variation on the outcome of
      HCV infection. We studied 322 subjects, 150 patients with persistent HCV
      infection, 63 individuals with spontaneous clearance and 109 healthy controls. In
      healthy subjects, we found a total of nine genotypes, with the 7/7 genotype being
      the most frequent (33%) followed by the 7/6 (22.9%) and the 7/5 (18.3%). The
      frequencies of the alleles were as follows: 7-LSIGN (56.4%), 6-LSIGN (20.2%), 5-L
      SIGN (18.3%) and 4-L-SIGN (5%). The frequency of the 7/4 genotype was higher in
      spontaneous resolvers (14.3%) as compared with the persistent group (4%) (OR =
      0.25, 95% CI = 0.07-0.82, p 0.022). In addition, we found that 4-L-SIGN was
      associated with spontaneous resolution of HCV infection (OR = 0.30, 95%CI, 0.12
      0.74, p 0.005). Interestingly, patients with 4-L-SIGN had lower viral loads when
      compared with carriers of the 5 (p 0.001), 6 (p 0.021) and 7-alleles (p 0.048).
      The results indicate that neck region polymorphism of L-SIGN can influence the
      outcome of HCV infection and the four-tandem repeat is associated with clearance
      of HCV infection.

PMID- 24283934
TI  - Multielectrode bisensor system for time-resolved monitoring of ion transport
      across an epithelial cell layer.
AB  - An ion-selective multielectrode bisensor system is designed to ensure reliable
      real-time concentration measurements of sodium, potassium, chloride, and pH in a
      small volume of biological liquid bathing a living human bronchial epithelial
      cell monolayer. The bisensor system allows the monitoring of major ions, which
      are simultaneously transported through the epithelia in both directions. 

PMID- 24283936
TI  - Measure of processes of care: a review of 20 years of research.
AB  - AIM: This article reviews literature on findings from the Measure of Processes of
      Care (MPOC) to assess family-centred services. METHOD: Systematic searches for
      papers citing MPOC in both PubMed and Web of Science identified 107 articles.
      Fifty-five met the criterion for inclusion in this review in that they reported
      MPOC data. RESULTS: Over the past 20 years MPOC has been used in settings
      additional to the children's treatment centres for which it was designed; used in
      11 countries and translated into 14 languages; and used to measure change in
      respondents' perceptions over time. MPOC findings have also informed our
      understanding of the provision of family-centred services. Overall, parents
      report that service providers do a good job of providing respectful,
      comprehensive services in partnership with families, but that there remain
      limitations in the provision of general information, an area for improvement.
      Finally, MPOC has been shown to correlate with various other measures related to
      the provision of family-centred services. INTERPRETATION: The MPOC 'family' of
      measures can be used to assess both families' and service providers' experiences
      and perceptions of the family-centredness of services received/provided.
      Opportunities abound for further research enquiries.

PMID- 24283935
TI  - Hyaluronic acid graft polymers displaying peptide antigen modulate dendritic cell
      response in vitro.
AB  - A novel oxime grafting scheme was utilized to conjugate an ICAM-1 ligand (LABL),
      a cellular antigen ovalbumin (OVA), or both peptides simultaneously to hyaluronic
      acid (HA). Samples of HA only and the various peptide grafted HA were found to
      bind to dendritic cells (DCs). HA with grafted LABL and OVA showed the greatest
      binding to DCs. Dendritic cells treated with HA, HA with grafted LABL, or HA with
      grafted LABL and OVA significantly suppressed T cell and DC conjugate formation
      and T cell proliferation and reduced proinflammatory cytokine production compared
      to untreated cells. These results suggest that HA serves as an effective backbone
      for multivalent ligand presentation for inhibiting T cell response to antigen
      presentation. In addition, multivalent display of both antigen and an ICAM-1
      inhibitor (LABL) may enhance binding to DCs and could potentially disrupt
      cellular signaling leading to autoimmunity. 

PMID- 24283937
TI  - Trichoderma asperelloides suppresses nitric oxide generation elicited by Fusarium
      oxysporum in Arabidopsis roots.
AB  - Inoculations with saprophytic fungus Trichoderma spp. are now extensively used
      both to promote plant growth and to suppress disease development. The underlying
      mechanisms for both roles have yet to be fully described so that the use of
      Trichoderma spp. could be optimized. Here, we show that Trichoderma asperelloides
      effects include the manipulation of host nitric oxide (NO) production. NO was
      rapidly formed in Arabidopsis roots in response to the soil-borne necrotrophic
      pathogen Fusarium oxysporum and persisted for about 1 h but is only transiently
      produced (approximately 10 min) when roots interact with T. asperelloides (T203).
      However, inoculation of F. oxysporum-infected roots with T. asperelloides
      suppressed F. oxysporum-initiated NO production. A transcriptional study of 78 NO
      modulated genes indicated most genes were suppressed by single and combinational
      challenge with F. oxysporum or T. asperelloides. Only two F. oxysporum-induced
      genes were suppressed by T. asperelloides inoculation undertaken either 10 min
      prior to or after pathogen infection: a concanavlin A-like lectin protein kinase
      (At4g28350) and the receptor-like protein RLP30. Thus, T. asperelloides can
      actively suppress NO production elicited by F. oxysporum and impacts on the
      expression of some genes reported to be NO-responsive. Of particular interest was
      the reduced expression of receptor-like genes that may be required for F.
      oxysporum-dependent necrotrophic disease development. 

PMID- 24283938
TI  - A novel, sensitive method to evaluate potato germplasm for bacterial wilt
      resistance using a luminescent Ralstonia solanacearum reporter strain.
AB  - Several breeding programs are under way to introduce resistance to bacterial wilt
      caused by Ralstonia solanacearum in solanaceous crops. The lack of screening
      methods allowing easy measurement of pathogen colonization and the inability to
      detect latent (i.e., symptomless) infections are major limitations when
      evaluating resistance to this disease in plant germplasm. We describe a new
      method to study the interaction between R. solanacearum and potato germplasm that
      overcomes these restrictions. The R. solanacearum UY031 was genetically modified
      to constitutively generate light from a synthetic luxCDABE operon stably inserted
      in its chromosome. Colonization of this reporter strain on different potato
      accessions was followed using life imaging. Bacterial detection in planta by this
      nondisruptive system correlated with the development of wilting symptoms. In
      addition, we demonstrated that quantitative detection of the recombinant strain
      using a luminometer can identify latent infections on symptomless potato plants.
      We have developed a novel, unsophisticated, and accurate method for high
      throughput evaluation of pathogen colonization in plant populations. We applied
      this method to compare the behavior of potato accessions with contrasting
      resistance to R. solanacearum. This new system will be especially useful to
      detect latency in symptomless parental lines before their inclusion in long-term
      breeding programs for disease resistance. 

PMID- 24283939
TI  - Enhanced nodulation and nodule development by nolR mutants of Sinorhizobium
      medicae on specific Medicago host genotypes.
AB  - The nolR gene encodes a negatively acting, transcriptional regulatory protein of
      core Nod-factor biosynthetic genes in the sinorhizobia. Although previous reports
      showed that nolR modulates Nod-factor production and enhances nodulation speed of
      Sinorhizobium meliloti on alfalfa, there have been no reports for the symbiotic
      function of this gene in the S. medicae-Medicago truncatula symbiosis. Here, we
      constructed an nolR mutant of S. medicae WSM419 and evaluated mutant and wild
      type strains for their nodulation ability, competitiveness, host specificity, and
      density-dependent nodulation phenotypes. When the mutant was inoculated at low
      and medium population densities, it showed enhanced nodule formation during the
      initial stages of nodulation. Results of quantitative competitive nodulation
      assays indicated that an nolR mutant had 2.3-fold greater competitiveness for
      nodulation on M. truncatula 'A17' than did the wild-type strain. Moreover, the
      nodulation phenotype of the nolR mutant differed among Medicago genotypes and
      showed significantly enhanced nodule development on M. tricycla. Taken together,
      these results indicated that mutation of nolR in S. medicae positively influenced
      nodule initiation, competitive nodulation, and nodule development at later
      nodulation stages. This may allow nolR mutants of S. medicae to have a selective
      advantage under field conditions. 

PMID- 24283941
TI  - Ultrafine ZnO nanoparticles/nanowires synthesized on a flexible and transparent
      substrate: formation, water molecules, and surface defect effects.
AB  - The ultrafine ZnO nanoparticles/nanowires were successfully synthesized on a
      flexible and transparent substrate by an ultraviolet-light decomposition process.
      We demonstrate that water molecules can affect the morphology of ZnO
      nanostructures. An ultraviolet lamp (lambda ~ 380 nm, 75 mW cm(-2)) can be used
      to irradiate Zn(AcAc)2 and Zn(AcAc)2.H2O precursors, which rapidly synthesize ZnO
      nanoparticles and nanowires, respectively. High-resolution transmission electron
      microscopy (HRTEM) images and a selected-area electron diffraction pattern
      revealed that the single-crystal nanoparticles were comprised of wurtzite
      structure ZnO. The nanowires consisted of ultrafine nanoparticles. On the basis
      of the Debye-Scherrer formula, the particle size of ZnO was calculated as ~6-9
      nm. The more water molecules the precursor had, the more OH(-) and Zn[(OH)4](2-)
      it put out. Moreover, due to the Zn[(OH)4](2-) and Zn(OH)2 species formed on the
      surface of the ZnO nanocrystals, they facilitated the one-dimensional nanowires
      during the crystal growth process. On the basis of our investigations, oxygen
      vacancies, hydroxyl, and zinc hydroxide all acted as key components in the
      formation processes that determined photoresponsive properties.

PMID- 24283940
TI  - Contrasting evolutionary patterns of spore coat proteins in two Bacillus species
      groups are linked to a difference in cellular structure.
AB  - BACKGROUND: The Bacillus subtilis-group and the Bacillus cereus-group are two
      well-studied groups of species in the genus Bacillus. Bacteria in this genus can
      produce a highly resistant cell type, the spore, which is encased in a complex
      protective protein shell called the coat. Spores in the B. cereus-group contain
      an additional outer layer, the exosporium, which encircles the coat. The coat in
      B. subtilis spores possesses inner and outer layers. The aim of this study is to
      investigate whether differences in the spore structures influenced the divergence
      of the coat protein genes during the evolution of these two Bacillus species
      groups. RESULTS: We designed and implemented a computational framework to compare
      the evolutionary histories of coat proteins. We curated a list of B. subtilis
      coat proteins and identified their orthologs in 11 Bacillus species based on
      phylogenetic congruence. Phylogenetic profiles of these coat proteins show that
      they can be divided into conserved and labile ones. Coat proteins comprising the
      B. subtilis inner coat are significantly more conserved than those comprising the
      outer coat. We then performed genome-wide comparisons of the
      nonsynonymous/synonymous substitution rate ratio, dN/dS, and found contrasting
      patterns: Coat proteins have significantly higher dN/dS in the B. subtilis-group
      genomes, but not in the B. cereus-group genomes. We further corroborated this
      contrast by examining changes of dN/dS within gene trees, and found that some
      coat protein gene trees have significantly different dN/dS between the B subtilis
      clade and the B. cereus-clade. CONCLUSIONS: Coat proteins in the B. subtilis- and
      B. cereus-group species are under contrasting selective pressures. We speculate
      that the absence of the exosporium in the B. subtilis spore coat effectively
      lifted a structural constraint that has led to relaxed negative selection
      pressure on the outer coat.

PMID- 24283942
TI  - A systematic review to assess cost effectiveness of enhanced recovery after
      surgery programmes in colorectal surgery.
AB  - AIM: Enhanced recovery after surgery (ERAS) programmes have been shown to reduce
      length of stay and peri-operative morbidity. However, there are comparatively few
      data on their cost effectiveness. The object of this systematic review was to
      appraise the current literature to determine the cost effectiveness of ERAS and
      to characterize how cost is reported and evaluated. METHOD: An electronic
      database search identified studies comparing ERAS with standard peri-operative
      care in colorectal surgery where an evaluation of cost effectiveness was a
      primary or secondary outcome. Cost data were converted to euros to enable a more
      standardized comparison of the studies. There were no limits on study design.
      RESULTS: Seven articles were included in the analysis. The reporting and
      evaluation of cost data were inconsistent. Reported cost for ERAS ranged from
      ?1989 to ?12,805 per patient. Although not all statistically significant, all
      studies demonstrated cost reductions with ERAS compared with non-ERAS although
      they were highly variable, ranging from ?153 to ?6537 per patient. CONCLUSION:
      Although the review has shown ERAS to be cost effective, there are some important
      inconsistencies and deficiencies regarding the reporting of data. Authors should
      therefore be encouraged to report cost data to supplement the literature
      detailing clinical efficacy.

PMID- 24283943
TI  - Increasing the diversity of U.S. conservation science professionals via the
      Society for Conservation Biology.

PMID- 24283945
TI  - Detection of bleeding disorders in Lebanon: outcomes of a pilot programme.
AB  - To promote management and awareness of bleeding disorders in Lebanon, a pilot
      programme was launched in 2009 by the Lebanese Hemophilia Association assisted by
      World Federation of Hemophilia. The aim of this study was to diagnose patients
      with bleeding disorders and to assess the potential challenges in implementing a
      screening programme. The pilot project was launched in 26 social health centres
      in the Bekaa valley. The study tools included the evaluation of the Tossetto
      Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for
      menstruation. Persons with a bleeding score higher than 2 and PBAC higher than
      185 were eligible for further blood tests including the prothrombin time, partial
      thromboplastin time, complete blood count, bleeding time and von Willebrand
      ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were
      women. Overall, 91 persons had an abnormal score. 50 eligible patients were
      tested: 32 had normal tests, nine new patients with severe Von Willebrand were
      discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There
      was a clear correlation between the severity of the score and the willingness to
      perform the tests (P = 0.02). Women were reluctant to participate fully when
      investigators were men. The probability of adherence to the screening protocol is
      significantly increased when directed by women health care professional. For
      patients with milder forms, global screening programmes were neither feasible nor
      acceptable but those more severely affected have to be identified. Providers are
      crucial in preselecting patients with blood problems who are not coping well.

PMID- 24283944
TI  - A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic
      fibrosis-specific lipid A.
AB  - Strains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic
      fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of
      lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the
      transfer of palmitate from outer membrane phospholipids to lipid A. This enzyme
      had previously been identified in many pathogenic Gram-negative bacteria, but in
      PA had remained elusive, despite abundant evidence that its lipid A contains
      palmitate. Using a combined genetic and biochemical approach, we identified
      PA1343 as the PA gene encoding PagP. Although PA1343 lacks obvious primary
      structural similarity with known PagP enzymes, the beta-barrel tertiary structure
      with an interior hydrocarbon ruler appears to be conserved. PA PagP transfers
      palmitate to the 3' position of lipid A, in contrast to the 2 position seen with
      the enterobacterial PagP. Palmitoylated PA lipid A alters host innate immune
      responses, including increased resistance to some antimicrobial peptides and an
      elevated pro-inflammatory response, consistent with the synthesis of a hexa
      acylated structure preferentially recognized by the TLR4/MD2 complex.
      Palmitoylation commonly confers resistance to cationic antimicrobial peptides,
      however, increased cytokine production resulting in inflammation is not seen with
      other palmitoylated lipid A, indicating a unique role for this modification in PA
      pathogenesis.

PMID- 24283946
TI  - Adjuvant zoledronic acid therapy for patients with early stage breast cancer: an
      updated systematic review and meta-analysis.
AB  - BACKGROUND: Zoledronic acid is a potent inhibitor of osteoclast-mediated bone
      resorption and has been widely used in bone metastasis malignancies and
      postmenopausal osteoporosis as a preventive therapy against skeletal-related
      events. The purpose of this study was to evaluate the clinical outcome of
      zoledronic acid as an adjuvant therapy for patients with early stage breast
      cancer. PATIENTS AND METHODS: Entries in the PubMed and EMBASE databases up to 12
      July 2013 were systematically reviewed. Online abstracts from the proceedings of
      the Annual Meetings of the American Society of Clinical Oncology (ASCO) (1992
      2013) and the San Antonio Breast Cancer Symposium (SABCS) (2004-2013) were also
      reviewed. Primary endpoints included overall survival (OS) and disease-free
      survival (DFS), while secondary endpoints included bone metastasis-free survival
      (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR).
      RESULTS: A total of eight studies including 3,866 subjects and 3,864 controls met
      our search criteria and were evaluated. The use of zoledronic acid was found to
      improve OS (relative risk (RR), 0.88; 95% confidence interval (CI), 0.77-1.01; p
      value = 0.06) and DMFS (RR, 0.77; 95% CI, 0.60-1.00; p-value = 0.05).
      Furthermore, statistically significant benefits were associated with BMFS (RR,
      0.81; 95% CI, 0.66-0.99; p-value = 0.04) and FFRs (RR, 0.75; 95% CI, 0.61-0.92; p
      value = 0.007). In contrast, there was no significant difference in DFS with the
      application of zoledronic acid (RR, 0.88; 95% CI, 0.72-1.09; p-value = 0.24).
      Sensitivity analysis further identified the improvement of 5-year OS for the
      adjuvant zoledronic acid therapy in early stage breast cancer patients (RR, 0.86;
      95% CI, 0.75-0.99; p-value = 0.03), while a borderline statistically significant
      benefit was observed for 5-year DFS (RR, 0.90; 95% CI, 0.81-1.00; p-value =
      0.06). CONCLUSION: Zoledronic acid as an adjuvant therapy appears to improve the
      5-year OS rate for early stage breast cancer patients, and was associated with a
      protective effect for the bone metastases and fractures evaluated in more than
      7,000 patients. However, further research is needed to confirm our findings, and
      sub-group analyses according to menopause status or hormone status may provide
      further insight.

PMID- 24283947
TI  - The role of macrophages polarization in predicting prognosis of radically
      resected gastric cancer patients.
AB  - Tumour-associated Macrophages (TAM) present two different polarizations:
      classical (M1) characterized by immunostimulation activity and tumour
      suppression; alternative (M2) characterized by tumour promotion and immune
      suppression. In this retrospective study, we evaluated the correlation between
      the two forms of TAM with survival time in radically resected gastric cancer
      patients. A total of 52 chemo- and radio-naive patients were included. Two slides
      were prepared for each patient and double-stained for CD68/NOS2 (M1) or
      CD68/CD163 (M2) and five representative high-power fields per slide were
      evaluated for TAM count. The median value of the two macrophage populations
      density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven
      patients with M1 density above-the-median had a significantly higher survival
      compared to those below the median. Twenty-six patients with M1/M2 ratio above
      the median showed median OS of 27.2 months compared to 15.5 months of the
      patients below the median. No association between M2 macrophage density and
      patient's outcome was found. In multivariate analysis, M1/M2 was a positive
      independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as
      confirmed in multivariate analysis, are factors that can help in predicting
      patients survival time after radical surgery for gastric cancer. 

PMID- 24283949
TI  - Targeting Neuregulin1 and HER receptor tyrosine kinases for therapy of breast
      cancer and heart failure.

PMID- 24283948
TI  - Effectiveness of newspaper advertising for patient recruitment into a clinical
      trial.
AB  - AIMS: To measure the impact of newspaper advertising across Scotland on patient
      interest, and subsequent recruitment into the Standard Care vs. Celecoxib Outcome
      Trial (SCOT), a clinical trial investigating the cardiovascular safety of non
      steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid
      arthritis. METHODS: Newspaper advertisements about the SCOT trial were placed
      sequentially in regional and national Scottish newspapers. The number of phone
      calls as a result of exposure to the advertisements and ongoing study recruitment
      rates were recorded before, during and after the advertising campaign. To enroll
      in SCOT individuals had to be registered with a participating GP practice.
      RESULTS: The total cost for the advertising campaign was L46 250 and 320 phone
      calls were received as a result of individuals responding to the newspaper
      advertisements. One hundred and seventy-two individuals were identified as
      possibly suitable to be included in the study. However only 36 were registered at
      participating GP practices, 17 completed a screening visit and 15 finally were
      randomized into the study. The average cost per respondent individual was L144
      and the average cost per randomized patient was L3083. Analysis of recruitment
      rate trends showed that there was no impact of the newspaper advertising campaign
      on increasing recruitment into SCOT. CONCLUSIONS: Advertisements placed in local
      and national newspapers were not an effective recruitment strategy for the SCOT
      trial. The advertisements attracted relatively small numbers of respondents, many
      of whom did not meet study inclusion criteria or were not registered at a
      participating GP practice.

PMID- 24283950
TI  - Tumor dormancy and the angiogenic switch: possible implications of bone marrow-
      derived cells.
AB  - Although escape from tumor dormancy has long been recognized as an important
      problem in the treatment of cancer, the molecular and cellular regulators
      underlying this transition remain poorly understood. The inability of the cancer
      cells to induce a complete and successful process of angiogenesis can result in
      tumor dormancy. In this case, the acquisition of sufficient angiogenic potential
      will result in the escape from indolence and in the initiation of tumor mass
      expansion. This stage in disease progression is known as the angiogenic switch.
      It is now becoming clear that the induction of the angiogenic switch is
      controlled by dynamic and complex biological processes involving the cancer
      cells, the associated stromal microenvironment and distant normal host cells,
      mostly from the bone marrow. Indeed, intricate tumor-host interactions are
      increasingly recognized as critical features of cancer. In particular,
      infiltrating cells of the immune system are crucial constituents of tumors and an
      important source of the growth stimulatory signals to the tumor cells. Tumor
      cells are surrounded by stromal cells, such as fibroblasts, lymphocytes,
      neutrophils, macrophages and mast cells, which communicate via a complex network
      of intercellular signaling pathways, mediated by surface adhesion molecules,
      cytokines and their receptors. However, the possible roles of these cells and
      molecules in the maintenance of micro-tumors in an occult state and in the
      induction of exit from the dormant state are not fully elucidated. In this
      review, we summarize recent findings and the current understanding of the role of
      bone marrow-derived cells, their recruitment into tumors and their interactive
      crosstalk with tumor cells, in leading to either the maintenance of, or exit
      from, tumor dormancy. Understanding the mechanisms of tumor growth and metastatic
      recurrence after periods of indolence is crucial for improving early detection,
      as well as increasing the cure rate for cancer patients. 

PMID- 24283951
TI  - The developing role of Neuregulin1 in cardiac regenerative stem cell therapy.
AB  - Myocardial infarction, heart failure, and chronic ischemic heart disease account
      for the majority of the cardiovascular burden. The current treatment strategies
      focus on limiting the progression of disease and preserving cardiac myocardium.
      The goal of stem cell therapy, on the other hand, is to reverse or replace
      damaged cardiac tissue. Over the past two decades many studies have been
      conducted to understand stem cell performance, survival, and the potential for
      cardiac repair. Neuregulin1, an epidermal growth factor family member, promotes
      embryonic stem cell differentiation into the cardiac lineage and improves
      survival in bone marrow-derived mesenchymal stem cell and embryonic endothelial
      progenitor cells. Current clinical trials are actively pursuing Neuregulin1's
      therapeutic potential in the areas of heart failure and cardiac ischemia. It is
      the intent of this paper to review the current knowledge of Neuregulin1 in stem
      cell biology and discuss the potential of using Neuregulin1 to improve stem cell
      therapy for cardiac repair.

PMID- 24283952
TI  - Neuregulin signaling in pieces--evolution of the gene family.
AB  - Paracrine and juxtacrine signaling via proteins expressed on the cell surface are
      an integral part of metazoan biology. More than one-half billion years ago
      epidermal growth factor (EGF) and its cognate receptor formed a functional
      binding partnership, which has been conserved through evolution in essentially
      all eubilaterate members of the animal kingdom. Early chordates spawned offspring
      of these seminal genes to begin the creation of new gene families and an expanded
      cell-cell signaling network, which included the Neuregulin (NRG) ligands and the
      erbB receptors. First appearance of ancestral NRG, represented in a NRG4-like
      gene in the lancelet Branchiostoma floridae, appears to have: 1) occurred in the
      common chordate ancestor prior to the divergence of lancelets (amphioxus), and;
      2) antedated the formation of the receptor gene family. Orthologues of NRG1 and
      multiple erbB receptors found in the sea lamprey Petromyzon marinus suggest that
      several key events, which were required to expand and diversify these gene
      families, occurred in the common ancestor of agnathostomes and jawed vertebrates.
      These important inventions surely played major roles in the acquisition of
      multiple apomorphic features of the emerging vertebrate lineage.

PMID- 24283953
TI  - Heregulin in breast cancer: old story, new paradigm.
AB  - Heregulin (HRG), a combinatorial ligand for the epidermal growth factor receptor
      family, is expressed in about 30% of breast cancer tumors. HRG induces
      tumorigenicity and metastasis of breast cancer cells and promotes hormone
      independent growth. Although HRG has been studied mostly in the context of the
      HRG receptor family, accumulating evidence suggests that HRG plays distinctive
      and causative roles in breast cancer tumorigenesis independent from the HRG
      receptors, demanding a comprehensive and independent study of HRG as a unique
      growth factor. This review provides a consolidated view of HRG and its biological
      role in the development, progression, and maintenance of breast cancer. Further,
      it provides further evidence that HRG is implicated in breast cancer resistance
      and targeting HRG may possibly be a beneficial tool to target a subgroup of
      breast carcinomas.

PMID- 24283954
TI  - Cardiovascular effects of neuregulin-1/ErbB signaling: role in vascular signaling
      and angiogenesis.
AB  - The NRG/erbB pathway has emerged as an important therapeutic target for cancer
      growth as well as cardiac related diseases. This discovery stems back to findings
      showing that overexpression of erbB2 receptors increases the metastatic potential
      of breast cancer in patients. Blocking this receptor using a monoclonal antibody
      (trastuzumab) inhibits tumor growth and offers significantly improved outcomes.
      However, excitement over this discovery was tempered by data showing that
      trastuzumab-treated patients have an increased risk of developing cardiac
      dysfunction, limiting the clinical potential of this novel agent. This finding
      suggested an important protective effect of the erbB signaling pathway on cardiac
      survival and homeostasis. Further investigation has shown that endothelial
      derived neuregulin (a key ligand for erbB receptors) has a protective paracrine
      effect on cardiac cells as well as vascular smooth muscle cells in the setting of
      an injury. Since endothelial cells contain erbB receptors, they are also targets
      for autocrine signaling via this pathway, an important mediator of vascular
      preservation and angiogenic responses of endothelium. In this review we summarize
      important clinical findings as well as animal and cellular models that illustrate
      the signaling pathways involved in vascular cell regulation of cardiomyocyte
      survival and angiogenesis via the NRG/erbB pathway.

PMID- 24283955
TI  - Mathematical modeling of tumor growth and treatment.
AB  - Using mathematical models to simulate dynamic biological processes has a long
      history. Over the past couple of decades or so, quantitative approaches have also
      made their way into cancer research. An increasing number of mathematical,
      physical, computational and engineering techniques have been applied to various
      aspects of tumor growth, with the ultimate goal of understanding the response of
      the cancer population to clinical intervention. So-called in silico trials that
      predict patient-specific response to various dose schedules or treatment
      combinations and sequencing are on the way to becoming an invaluable tool to
      optimize patient care. Herein we describe fundamentals of mathematical modeling
      of tumor growth and tumor-host interactions, and summarize some of the seminal
      and most prominent approaches. 

PMID- 24283956
TI  - Breast cancer biomarkers: risk assessment, diagnosis, prognosis, prediction of
      treatment efficacy and toxicity, and recurrence.
AB  - Breast cancer is the most common cancer amongst women in the United States and
      around the world. Although widespread use of adjuvant chemotherapeutic and
      hormonal agents has improved mortality from breast cancer, it remains challenging
      to determine on an individual basis who will benefit from such treatments and who
      will be likely to encounter toxicities. With the rising costs of healthcare and
      the introduction of new targeted therapies, use of biomarkers has emerged as a
      method of assisting with breast cancer diagnosis, prognosis, prediction of
      therapeutic response, and surveillance of disease during and after treatment. In
      the following review, prognostic and therapeutic biomarkers, their utility in the
      management of patients with breast cancer, and current recommendations regarding
      their clinical use will be discussed. 

PMID- 24283957
TI  - Compliance with the International Code of Marketing of breast-milk substitutes:
      an observational study of pediatricians' waiting rooms.
AB  - Abstract The importance of breastmilk as a primary preventative intervention is
      widely known and understood by most healthcare providers. The actions or non
      actions that heathcare providers take toward promoting and supporting
      breastfeeding families make a difference in the success and duration of
      breastfeeding. Recognizing this relationship, the World Health Organization
      developed the International Code of Marketing of Breast-milk Substitutes (the
      Code), which defines best practices in breastfeeding promotion, including
      physicians' offices. The pediatric practices' waiting rooms are often a family's
      first experience with pediatric care. The specific aims of this study were to
      describe (1) Code compliance, (2) the demographic factors affecting the Code
      compliance, and (3) the amount and type of breastfeeding-supportive materials
      available in the pediatricians' waiting rooms. An observational cross-sectional
      design was used to collect data from 163 (82%) of the pediatric practices in
      Maricopa County, Arizona. None of the 100 waiting rooms that had any materials
      displayed (61%) was found to be completely Code compliant, with 81 of the offices
      having formula-promotional materials readily available. Waiting rooms in higher
      income areas offered more non-Code-compliant materials and gifts. Breastfeeding
      support information and materials were lacking in all but 18 (18%) offices. A
      positive relationship (t97=-2.31, p=0.02) occurred between the presence of
      breastfeeding educational materials and higher income areas. We were able to
      uncover some practice-related patterns that impact families and potentially
      undermine breastfeeding success. To move current practices toward breastfeeding
      friendly physicians' offices, change is needed. 

PMID- 24283958
TI  - Maternal age and breastfeeding at 1 month after delivery at a Japanese hospital.

PMID- 24283959
TI  - Secular trends in impact factor of breastfeeding research publications over a 20
      year period.
AB  - OBJECTIVE: The aim of the current study was to determine whether secular changes
      have occurred in the breastfeeding literature, in terms of number and type of
      yearly published articles and impact factor of journals publishing these
      articles. RESEARCH DESIGN AND SETTING: In order to evaluate all Medline articles
      related to breastfeeding, we used the Internet URL www.ncbi.nlm.nih.gov/entrez
      and searched for articles recorded from January 1, 1992 through December 31, 2011
      using as a key word "breast milk," "breast feeding," or "human milk." We
      specifically studied randomized controlled trials (RCTs), clinical trials, case
      reports, meta-analyses, letters to the editor, reviews, systematic reviews,
      practice guidelines, and editorials. RESULTS: There was a linear increase over
      the years in all articles recorded, from approximately 1,100/year in 1992 to
      2,100/year in 2011 (i.e., an approximately 1.9-fold increase [R(2)=0.995,
      p=0.001]). Concomitant with the yearly increase in the number of published RCTs
      per year, there was a linear increase in the number of journals publishing
      articles on breastfeeding per year (from approximately 20 in 1992 to >60 in 2011
      [R(2)=0.811, p<0.001]) but an overall decrease in the average impact factor every
      year (R(2)=0.202, p=0.047). However, the ratio of high-quality articles selected
      (RCTs+meta-analyses+systematic reviews+CR)/low-quality articles
      (reviews+editorials+letters to the editor+case reports) increased significantly
      over time in favor of the former. CONCLUSIONS: There was a linear increase in the
      number of publications related to the field of breastfeeding and human milk, and
      the ratio of high-quality/low-quality articles improved over time, indicating a
      relative and absolute increase in the number of articles usually considered as
      being of high quality. There was a significant increase in the number of journals
      publishing breastfeeding-related articles, with a significant decrease of average
      impact factor of those journals.

PMID- 24283960
TI  - Crystal polymorphs of barbital: news about a classic polymorphic system.
AB  - Barbital is a hypnotic agent that has been intensely studied for many decades.
      The aim of this work was to establish a clear and comprehensible picture of its
      polymorphic system. Four of the six known solid forms of barbital (denoted I(0),
      III, IV, and V) were characterized by various analytical techniques, and the
      thermodynamic relationships between the polymorph phases were established. The
      obtained data permitted the construction of the first semischematic
      energy/temperature diagram for the barbital system. The modifications I(0), III,
      and V are enantiotropically related to one another. Polymorph IV is
      enantiotropically related to V and monotropically related to the other two forms.
      The transition points for the pairs I(0)/III, I(0)/V, and III/IV lie below 20 
      degrees C, and the transition point for IV/V is above 20  degrees C. At room
      temperature, the order of thermodynamic stability is I(0) > III > V > IV. The
      metastable modification III is present in commercial samples and has a high
      kinetic stability. The solid-state NMR spectra provide information on aspects of
      crystallography (viz., the asymmetric units and the nature of hydrogen bonding).
      The known correlation between specific N-H...O?C hydrogen bonding motifs of
      barbiturates and certain IR characteristics was used to predict the H-bonded
      pattern of polymorph IV. 

PMID- 24283961
TI  - Radiolabeled peptides for Alzheimer's diagnostic imaging: mini review.
AB  - The pathology of Alzheimer's disease (AD) is characterized by the extracellular
      and intracellular accumulation of amyloid-beta (Abeta) fibrillar plaques formed
      by the Abeta1-42 peptide, neurofibrillary tangles (NFTs) consisting of
      hyperphosphorylated tau, extensive neuritic and synaptic degradation, and neuron
      loss. One of the priorities for the treatment of AD is both the early detection
      and accurate chart progression of the accumulation of Abeta plaques in human
      brains. Molecular imaging tools can provide an in vivo visualization of Abeta
      plaques. Specific identification of amyloid plaques would allow a more accurate
      prognosis and ensure more effective clinical trials of anti-amyloid agents at
      earlier disease stage. The emphasis of this review is on the development of Abeta
      peptide radiopharmaceuticals or the ones combined with nanocarrier-based such as
      Molecular Trojan horses or nanoparticles for applications in in vivo amyloid
      imaging in AD.

PMID- 24283962
TI  - PET radiotracers for molecular imaging in dementia.
AB  - Molecular imaging with various biomarkers plays a significant role in the
      diagnostic assessment of patients with dementing disorders, by detecting
      functional and pathophysiologic changes in the brain. PET imaging, in particular,
      allows the measurements of different molecular targets, such as functional
      markers of neurodegeneration (glucose metabolism), markers for pathological
      aggregates (such as amyloid, tau and synuclein aggregates) and neuroinflammation,
      and also markers of several neurotransmission systems. In the current view,
      neurodegenerative diseases are associated with the development of pathologic
      changes that play a different role in disease onset and evolution, often starting
      long before the onset of clinically detectable impairment. Molecular imaging
      represents thus a unique tool to collect relevant information contributing to
      accurate diagnosis, treatment and response monitoring. In this article, we review
      the current literature focusing on the PET radiotracers used for molecular
      imaging in dementia. 

PMID- 24283963
TI  - Role of ozone in UV-C disinfection, demonstrated by comparison between wild-type
      and mutant conidia of Aspergillus niger.
AB  - This study aimed to investigate the tolerance of a melanized wild-type strain of
      Aspergillus niger (CON1) and its light-colored mutant (MUT1) to UV-C light and
      the concomitantly generated ozone. Treatments were segregated into four groups
      based on whether UV irradiation was used and the presence or absence of ozone: (
      UV, -O3), (-UV, +O3), (+UV, -O3) and (+UV, +O3). The survival of CON1 and MUT1
      conidia under +UV decreased as the exposure time increased, with CON1 showing
      greater resistance to UV irradiation than MUT1. Ozone induced CON1 conidium
      inactivation only under conditions of UV radiation exposure. While, the
      inactivation effect of ozone on MUT1 was always detectable regardless of the
      presence of UV irradiation. Furthermore, the CON1 conidial suspension showed
      lower UV light transmission than MUT1 when examined at the same concentration.
      Compared with the pigment in MUT1, the melanin in CON1 exhibited more potent
      radical-scavenging activity and stronger UV absorbance. These results suggested
      that melanin protected A. niger against UV disinfection via UV screening and free
      radical scavenging. The process by which UV-C disinfection induces a continual
      decrease in conidial survival suggests that UV irradiation and ozone exert a
      synergistic fungicidal effect on A. niger prior to reaching a plateau.

PMID- 24283964
TI  - Executive functions and intraindividual variability following concussion.
AB  - The long-term outcomes of executive functions and intraindividual variability
      (IIV; i.e., trial-to-trial or across-task variability in cognitive performance)
      following concussion are unclear due to inconsistent and limited research
      findings, respectively. OBJECTIVE: Responding to these gaps in scientific
      understanding, the current study aimed to assess the utility of both executive
      functions and IIV at predicting concussion history. METHOD: Altogether 138 self
      identified athletes (Mage = 19.9 +/- 1.91 years, 60.8% female, 19.6% with one
      concussion, 18.1% with two or more concussions) completed three executive-related
      cognitive tasks (i.e., n-back, go/no-go, global-local). Ordinal logistic
      regression analyses examined the joint effect of person-mean and IIV as
      predictors of concussion status. RESULTS: Only mean response time for the global
      local task predicted the number of past concussions, while no IIV variables
      reached unique significance. CONCLUSIONS: IIV research on concussion remains
      limited; however, the preliminary results do not indicate any additional value of
      IIV indices above mean performances at predicting past concussion. For executive
      functions, shifting appears most sensitive at detecting concussion group
      differences, with past researchers identifying post concussion impairment in
      attentional processing.

PMID- 24283965
TI  - High-performance liquid chromatography with fluorescence detection for the
      determination of nitrofuran metabolites in pork muscle.
AB  - A simple and sensitive HPLC method with fluorescence detection (HPLC-FLD) is
      reported for the simultaneous determination of metabolites of four nitrofuran
      drugs (furazolidone, furaltadone, nitrofurantoin and nitrofurazone) in pork
      muscle. The method involves acid hydrolysis of the protein-bound drug metabolites
      and the conjugation of the released side-chains with a novel fluorescence agent 2
      hydroxy-1-naphthaldehyde. After liquid-liquid extraction and effective separation
      of the derivatives on a YMC-Pack Polymer C18 column at 40 degrees C under
      alkaline conditions, the high fluorescence intensity of these derivatives at
      emission wavelength lambdaem = 463 nm enables their simultaneous determination in
      pork muscle at concentrations as low as 1 ug kg-1. The method was validated using
      blank pork muscle fortified with all four metabolites at 0.5, 1.0 and 2.0 ug kg
      1. Recoveries were > 92.3% with RSDs < 8.5% for all four metabolites. The results
      obtained with HPLC-FLD and LC-MS/MS methods showed very good agreement for pork
      muscle samples.

PMID- 24283966
TI  - Annexation of a high-activity enzyme in a synthetic three-enzyme complex greatly
      decreases the degree of substrate channeling.
AB  - The self-assembled three-enzyme complex containing triosephosphate isomerase
      (TIM), aldolase (ALD), and fructose 1,6-biphosphatase (FBP) was constructed via a
      mini-scaffoldin containing three different cohesins and the three dockerin
      containing enzymes. This enzyme complex exhibited 1 order of magnitude higher
      initial reaction rates than the mixture of noncomplexed three enzymes. In this
      enzyme cascade reactions, the reaction mediated by ALD was the rate-limiting
      step. To understand the in-depth role of the rate-limiting enzyme ALD in
      influencing the substrate channeling effect of synthetic enzyme complexes, low
      activity ALD from Thermotoga maritima was replaced with a similar-size ALD
      isolated from Thermus thermophilus, where the latter had more than 5 times
      specific activity of the former. The synthetic three-enzyme complexes annexed
      with either low-activity or high-activity ALDs exhibited higher initial reaction
      rates than the mixtures of the two-enzyme complex (TIM-FBP) and the nonbound low
      activity or high activity ALD at the same enzyme concentration. It was also found
      that the annexation of more high-activity ALD in the synthetic enzyme complexes
      drastically decreased the degree of substrate channeling from 7.5 to 1.5. These
      results suggested that the degree of substrate channeling in synthetic enzyme
      complexes depended on the enzyme choice. This study implied that the construction
      of synthetic enzyme enzymes in synthetic cascade pathways could be a very
      important tool to accrelerate rate-limiting steps controlled by low-activity
      enzymes. 

PMID- 24283968
TI  - Foundation-industry relationships--a new business model joint-venture
      philanthropy in therapy development.
AB  - The business model for medical therapy development has changed drastically. Large
      companies that once conducted their own Research and Development (R&D) and funded
      all the preclinical studies, all phases of clinical development and marketing of
      the products are increasingly turning to others for more and more of the earlier
      work in hopes of being able to in-license a de-risked program well downstream,
      take it through the final phases of clinical development and into the
      marketplace. This new paradigm has required patient-advocacy foundations,
      especially in the rare-disease space, to become far more effective in building
      relationships with all the players along the therapy-development pathway --
      academic scientists, government agencies, other foundations with overlapping
      interests, biotechs, small biopharmaceutical entities and even the larger
      industry companies. From the perspective of the patient-advocacy community, these
      increasingly essential public-private partnerships have taken on the nature of
      what could be called joint-venture philanthropy and involve a broad spectrum of
      collaborations and financial relationships between foundations and industry
      partners that are not without concerns about potential conflicts of interest. 

PMID- 24283967
TI  - A systematic review of hospitalization resulting from medicine-related problems
      in adult patients.
AB  - AIMS: Medicine-related problems (MRPs) represent a major issue leading to
      hospitalization, especially in adult and elderly patients. The aims of this
      review are to investigate the prevalence, causes and major risk factors for MRPs
      leading to hospitalization in adult patients and to identify the main medicine
      classes involved. METHODS: Studies were identified through electronic searches of
      Medline, Embase, Scopus and International Pharmaceutical Abstracts between
      January 2000 and May 2013. A systematic review was conducted of both
      retrospective and prospective studies. Studies included were those involving
      hospitalization resulting from MRPs in adults (>=18 years old), whereas studies
      excluded were those investigating drug misuse and abuse and studies investigating
      MRPs in hospitalized patients. Data analysis was performed using SPSS version 20.
      RESULTS: Forty-five studies were identified, including 21 that investigated
      hospitalization resulting from adverse drug reactions, six studies that
      investigated hospitalization due to adverse drug events and 18 studies that
      investigated hospitalization due to MRPs. The median prevalence rates of
      hospitalization resulting from adverse drug reactions, adverse drug events and
      MRPs were 7% (interquartile range, 2.4-14.9%), 4.6% (interquartile range, 2.85
      16.6%) and 12.1% (interquartile range, 6.43-22.2%), respectively. The major
      causes contributing to MRPs were adverse drug reactions and noncompliance. In
      addition, the major risk factors associated with MRPs were old age, polypharmacy
      and comorbidities. Moreover, the main classes of medicines implicated were
      medicines used to treat cardiovascular diseases and diabetes. CONCLUSIONS:
      Hospitalization due to MRPs had a high prevalence, in the range of 4.6-12.1%.
      Most MRPs encountered were prevalent among adult patients taking medicines for
      cardiovascular diseases and diabetes.

PMID- 24283969
TI  - Seeding collaborations to advance kinase science with the GSK Published Kinase
      Inhibitor Set (PKIS).
AB  - To catalyze research on historically untargeted protein kinases, we created the
      PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been
      widely distributed to academic collaborators as an open access tool. It has been
      used to identify chemical starting points for development of chemical probes for
      orphan kinases and to investigate kinase signaling in high content phenotypic
      assays. Access to the set comes with few restrictions other than the requirement
      that assay results be released into the public domain for the benefit of the
      entire research community. Examples from the efforts of several collaborators are
      summarized. 

PMID- 24283971
TI  - Leveraging public private partnerships to innovate under challenging budget
      times.
AB  - The National Institutes of Health (NIH), academic medical centers and industry
      have a long and productive history in collaborating together. Decreasing R&D
      budgets in both the private and public sector have made the need for such
      collaborations paramount to reduce the risk of further declines in the number of
      innovative drugs reaching the market to address pressing public health needs.
      Doing more with less has forced both industry and public sector research
      institutions (PSRIs) to leverage resources and expertise in order to de-risk
      projects. In addition, it provides an opportunity to envision and implement new
      approaches to accomplish these goals. We discuss several of these innovative
      collaborations and partnerships at the NIH that demonstrate how the NIH and
      industry are working together to strengthen the drug development pipeline. 

PMID- 24283970
TI  - Collaborative development of 2-hydroxypropyl-beta-cyclodextrin for the treatment
      of Niemann-Pick type C1 disease.
AB  - In 2010, the National Institutes of Health (NIH) established the Therapeutics for
      Rare and Neglected Diseases (TRND) program within the National Center for
      Advancing Translational Sciences (NCATS), which was created to stimulate drug
      discovery and development for rare and neglected tropical diseases through a
      collaborative model between the NIH, academic scientists, nonprofit
      organizations, and pharmaceutical and biotechnology companies. This paper
      describes one of the first TRND programs, the development of 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) for the treatment of Niemann-Pick disease type C1
      (NPC1). NPC is a neurodegenerative, autosomal recessive rare disease caused by a
      mutation in either the NPC1 (about 95% of cases) or the NPC2 gene (about 5% of
      cases). These mutations affect the intracellular trafficking of cholesterol and
      other lipids, which leads to a progressive accumulation of unesterified
      cholesterol and glycosphingolipids in the CNS and visceral organs. Affected
      individuals typically exhibit ataxia, swallowing problems, seizures, and
      progressive impairment of motor and intellectual function in early childhood, and
      usually die in adolescence. There is no disease modifying therapy currently
      approved for NPC1 in the US. A collaborative drug development program has been
      established between TRND, public and private partners that has completed the pre
      clinical development of HP-beta-CD through IND filing for the current Phase I
      clinical trial that is underway. Here we discuss how this collaborative effort
      helped to overcome scientific, clinical and financial challenges facing the
      development of new drug treatments for rare and neglected diseases, and how it
      will incentivize the commercialization of HP-beta-CD for the benefit of the NPC
      patient community. 

PMID- 24283972
TI  - A unique industrial-academic collaboration towards the next generation of
      schizophrenia therapeutics.
AB  - This article describes the unique industrial-academic collaboration that has been
      running for four years between Janssen Pharmaceutica NV and the Vanderbilt Center
      for Neuroscience Drug Discovery (VCNDD) towards identifying the next generation
      of schizophrenia therapeutics. This was a true collaboration, with both entities
      engaged in chemistry, In vitro pharmacology, DMPK and In vivo behavioral
      pharmacology, and aligned to deliver a first-in-class clinical candidate (NME)
      and additional back-up molecules. Notably, a first NME was delivered in a rapid
      timeframe and targeted the novel mechanism of mGlu5 positive allosteric
      modulation. As with any true collaboration, both sides brought unique skills to
      the table--Janssen leveraged deep drug discovery expertise and infrastructure,
      while Vanderbilt brought deep knowledge of the chemistry and pharmacology of the
      target in addition to the ability to provide deep scientific insight into the
      mechanism behind target modulation. In this article, we will discuss the science
      which drove our collaboration as well as some key lessons learned.

PMID- 24283973
TI  - Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic
      chemical space.
AB  - The continued development of computational and synthetic methods has enabled the
      enumeration or preparation of a nearly endless universe of chemical structures.
      Nevertheless, the ability of this chemical universe to deliver small molecules
      that can both modulate biological targets and have drug-like physicochemical
      properties continues to be a topic of interest to the pharmaceutical industry and
      academic researchers alike. The chemical space described by public, commercial,
      in-house and virtual compound collections has been interrogated by multiple
      approaches including biochemical, cellular and virtual screening, diversity
      analysis, and in-silico profiling. However, current drugs and known chemical
      probes derived from these efforts are contained within a remarkably small volume
      of the predicted chemical space. Access to more diverse classes of chemical
      scaffolds that maintain the properties relevant for drug discovery is certainly
      needed to meet the increasing demands for pharmaceutical innovation. The Lilly
      Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to
      innovation through the identification of novel molecules active in relevant
      disease biology models. In this article we will discuss several computational
      approaches towards describing novel, biologically active, drug-like chemical
      space and illustrate how the OIDD program may facilitate access to previously
      untapped molecules that may aid in the search for innovative pharmaceuticals. 

PMID- 24283974
TI  - Playing well with others! Initiating and sustaining successful collaborations
      between industry, academia and government.

PMID- 24283975
TI  - Antifungal pre-emptive strategy for high-risk neutropenic patients: why the story
      is still ongoing.
AB  - Neutropenic patients with haematological malignancies are at high risk of
      invasive fungal disease (IFD). Due to limitations in specific procedures to
      establish an early diagnosis of IFD, two historical unpowered studies suggested,
      three decades ago, that giving an empirical antifungal treatment to patients with
      persistent or recurrent fever under broad-spectrum antibacterials, could reduce
      the risk of IFD. For cost and toxicity reasons, this strategy became debated when
      modern imaging and indirect biological markers became available. Different pre
      emptive strategies, either based on lung imaging, galactomannan antigenaemia,
      fungal PCR, or a combination of several parameters, were designed with the goal
      of restricting the administration of antifungals to the more at-risk patients
      with early signs of IFD. Almost all pre-emptive studies showed or suggested a
      reduction of administration and cost of antifungals during neutropenic phases.
      However, the clinical pertinence and safety of the strategy, and mainly its
      optimal design, are still pending. This paper reviews the evolution of these
      strategies and how they may be implemented in the haematology ward.

PMID- 24283976
TI  - Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression
      of thymic stromal lymphopoietin in allergic mice with established experimental
      asthma.
AB  - BACKGROUND: Rhinovirus infection or dsRNA stimulation increased thymic stromal
      lymphopoietin (TSLP), an upstream pro-allergic cytokine, in asthmatic bronchial
      epithelial cells. We hypothesized that dsRNA challenges superimposed on
      established experimental allergic asthma constitute a useful exacerbation model.
      We further hypothesized that TSLP is induced at dsRNA- and rhinoviral infection
      induced exacerbations. METHODS: Allergic mice were challenged with OVA followed
      by three daily intranasal challenges with dsRNA or saline. Bronchoalveolar lavage
      fluid (BALF) was analysed for total protein, lactate dehydrogenase (LDH),
      CXCL1/KC, CCL2/MCP-1 and differential cell counts. Lung tissue histology,
      neutrophils and TSLP, TNF-alpha, IFN-beta and IFN-lambda mRNA were examined.
      Alternatively, allergen-challenged mice received intranasal rhinovirus-(RV)-1B
      followed by lung TSLP immunostaining. RESULTS: In mice with allergic airway
      inflammation, dsRNA challenges caused a significant exacerbation increasing lung
      tissue inflammation score and tissue neutrophilia. Bronchoalveolar lavage fluid
      neutrophils, total protein, LDH, CXCL1/KC and CCL2/MCP-1 were also increased (P <
      0.01), and so were lung tissue expressions of TNF-alpha, IFN-lambda and TSLP (P <
      0.01), but IFN-beta was not increased. TSLP, IFN-lambda and LDH were not
      increased by allergen or dsRNA challenges alone, but increased exclusively at
      exacerbations. RV1B infection-induced exacerbation also increased lung tissue
      TSLP (P < 0.05). CONCLUSIONS: dsRNA-induced exacerbation in mice with
      experimental asthma involved general inflammation, cytokines and interferons, in
      agreement with previous observations in exacerbating human asthma. Additionally,
      both dsRNA and RV1B infection increased lung TSLP exclusively at exacerbations.
      Our data suggest that dsRNA challenges superimposed on allergic inflammation are
      suited for pharmacological studies of asthma exacerbations including the
      regulation of lung tissue TSLP, TNF-alpha, IFN-beta and IFN-lambda.

PMID- 24283978
TI  - A systems medicine research approach for studying alcohol addiction.
AB  - According to the World Health Organization, about 2 billion people drink alcohol.
      Excessive alcohol consumption can result in alcohol addiction, which is one of
      the most prevalent neuropsychiatric diseases afflicting our society today.
      Prevention and intervention of alcohol binging in adolescents and treatment of
      alcoholism are major unmet challenges affecting our health-care system and
      society alike. Our newly formed German SysMedAlcoholism consortium is using a new
      systems medicine approach and intends (1) to define individual neurobehavioral
      risk profiles in adolescents that are predictive of alcohol use disorders later
      in life and (2) to identify new pharmacological targets and molecules for the
      treatment of alcoholism. To achieve these goals, we will use omics-information
      from epigenomics, genetics transcriptomics, neurodynamics, global neurochemical
      connectomes and neuroimaging (IMAGEN; Schumann et al. ) to feed mathematical
      prediction modules provided by two Bernstein Centers for Computational
      Neurosciences (Berlin and Heidelberg/Mannheim), the results of which will
      subsequently be functionally validated in independent clinical samples and
      appropriate animal models. This approach will lead to new early intervention
      strategies and identify innovative molecules for relapse prevention that will be
      tested in experimental human studies. This research program will ultimately help
      in consolidating addiction research clusters in Germany that can effectively
      conduct large clinical trials, implement early intervention strategies and impact
      political and healthcare decision makers. 

PMID- 24283977
TI  - Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic.
AB  - Many Gram-negative bacteria interact with extracellular metal ions by expressing
      one or more siderophore types. Among these, the virulence-associated siderophore
      yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu(II)
      Ybt) complexes that are detectable in infected patients. Here we show that Ybt
      expressing E. coli are protected from intracellular killing within copper-replete
      phagocytic cells. This survival advantage is highly dependent upon the phagocyte
      respiratory burst, during which superoxide is generated by the NADPH oxidase
      complex. Chemical fractionation links this phenotype to a previously
      unappreciated superoxide dismutase (SOD)-like activity of Cu(II)-Ybt. Unlike
      previously described synthetic copper-salicylate (Cu(II)-SA) SOD mimics, the
      salicylate-based natural product Cu(II)-Ybt retains catalytic activity at
      physiologically plausible protein concentrations. These results reveal a new
      virulence-associated adaptation based upon spontaneous assembly of a non-protein
      catalyst. 

PMID- 24283979
TI  - The role of ghrelin in drug and natural reward.
AB  - Ghrelin is a protein that has been given special attention in both nutrition and
      addiction research during the last decade. Consequently, a vast amount of
      information has been accumulated concerning the role of ghrelin in natural and
      drug reward. We are now in the position to ask whether the ghrelin system could
      be targeted to treat maladaptive behaviours such as obesity and drug addiction.
      Indeed, ghrelin research has demonstrated that blocking the activity of ghrelin
      receptors may be effective in reducing the consumption of both food and drugs of
      abuse. This review will give a short overview of our current knowledge about the
      ghrelin system in the context of drug and natural rewards as well as the
      possibility of developing potential ghrelin-based treatments. 

PMID- 24283980
TI  - Sodium oxybate to treat alcohol dependence: 20 years of clinical experience.

PMID- 24283981
TI  - The role of the endocannabinoid system in addictive behavior.

PMID- 24283982
TI  - Evaluation of plasma-free endocannabinoids and their congeners in abstinent
      cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity.
AB  - Cocaine is associated with serious health problems including psychiatric co
      morbidity. There is a need for the identification of biomarkers for the
      stratification of cocaine-addicted subjects. Several studies have evaluated
      circulating endocannabinoid-related lipids as biomarkers of inflammatory,
      metabolic and mental disorders. However, little is known in substance use
      disorders. This study characterizes both free N-acyl-ethanolamines (NAEs) and 2
      acyl-glycerols in abstinent cocaine addicts from outpatient treatment programs
      who were diagnosed with cocaine use disorder (CUD; n = 88), and age-/gender-/body
      mass-matched healthy control volunteers (n = 46). Substance and mental disorders
      that commonly occur with substance abuse were assessed by the semi-structured
      interview 'Psychiatric Research Interview for Substance and Mental Diseases'
      according to the 'Diagnostic and Statistical Manual of Mental Disorders, 4th
      Edition, Text Revision' (DSM-IV-TR) and plasma-free acyl derivatives were
      quantified by a liquid chromatography-tandem mass spectrometry system. The
      results indicate that plasma acyl derivatives are altered in abstinent cocaine
      addicted subjects with CUD (CUD subjects). While NAEs were found to be increased,
      2-acyl-glycerols were decreased in CUD subjects compared with controls.
      Multivariate predictive models based on these lipids as explanatory variables
      were developed to distinguish CUD subjects from controls providing high
      discriminatory power. However, these alterations were not influenced by the DSM
      IV-TR criteria for cocaine abuse and dependence as cocaine trait severity
      measure. In contrast, we observed that some free acyl derivatives in CUD subjects
      were found to be affected by the diagnosis of some co-morbid psychiatric
      disorders. Thus, we found that the monounsaturated NAEs were significantly
      elevated in CUD subjects diagnosed with mood [N-oleoyl-ethanolamine and N
      palmitoleoyl-ethanolamine (POEA)] and anxiety (POEA) disorders compared with non
      co-morbid CUD subjects. Interestingly, the coexistence of alcohol use disorders
      did not influence the circulating levels of these free acyl derivatives. In
      summary, we have identified plasma-free acyl derivatives that might serve as
      reliable biomarkers for CUD. Furthermore, we found that monounsaturated NAE
      levels are also enhanced by co-morbid mood and anxiety disorders in cocaine
      addicts. These findings open the way for the development of new strategies for
      cocaine addiction diagnosis and treatment. 

PMID- 24283983
TI  - Evaluation of nestin in lung adenocarcinoma: relation to VEGF and Bcl-2.
AB  - CONTEXT: Nestin is a marker of multipotent precursor cells that is up regulated
      in cancer. OBJECTIVE: To explore its diagnostic role and its relationship to
      vascular endothelial growth factor (VEGF) and Bcl-2 in lung adenocarcinoma.
      MATERIALS AND METHODS: Evaluation of nestin expression in lung biopsies by real
      time PCR and serum VEGF and Bcl-2 by ELISA in 27 adenocarcinoma patients and 15
      control subjects. RESULTS: Nestin was significantly higher in lung adenocarcinoma
      patients especially with advanced grade and stage and it was significantly
      correlated to VEGF and Bcl-2. CONCLUSION: Nestin can be considered as a potential
      diagnostic marker in lung adenocarcinoma.

PMID- 24283984
TI  - Evaluation of elevated urinary enolase I levels in patients with endometriosis.
AB  - OBJECTIVE: The aim of this study is to validate and investigate the clinical
      value of urinary enolase I in patients with endometriosis. METHODS: Urine samples
      of 39 patients with histologically confirmed endometriosis and 20 patients
      without endometriosis were collected. Western blot analysis and enzyme-linked
      immunosorbent assay were used to detect the increase of enolase I in patients'
      urine. RESULTS: Urinary enolase I expression corrected for creatinine ratio (non
      neuronal enolase (NNE)-Cr) was significantly greater in patients with
      endometriosis (p = 0.026). When the diagnostic performance of NNE-Cr was
      evaluated with serum CA-125 combination, the area under the curve was 0.821 (95%
      confidence interval 0.713-0.928) with sensitivity and specificity of 76.9% and
      85.0%, respectively. CONCLUSION: Elevated urinary enolase I, in conjunction with
      serum CA-125, may be used as a potential biomarker for endometriosis.

PMID- 24283986
TI  - Exploring the proteomic landscape of a gastric cancer biopsy with the shotgun
      imaging analyzer.
AB  - Accessing localized proteomic profiles has emerged as a fundamental strategy to
      understand the biology of diseases, as recently demonstrated, for example, in the
      context of determining cancer resection margins with improved precision. Here, we
      analyze a gastric cancer biopsy sectioned into 10 parts, each one subjected to
      MudPIT analysis. We introduce a software tool, named Shotgun Imaging Analyzer and
      inspired in MALDI imaging, to enable the overlaying of a protein's expression
      heat map on a tissue picture. The software is tightly integrated with the
      NeXtProt database, so it enables the browsing of identified proteins according to
      chromosomes, quickly listing human proteins never identified by mass spectrometry
      (i.e., the so-called missing proteins), and the automatic search for proteins
      that are more expressed over a specific region of interest on the biopsy, all of
      which constitute goals that are clearly well-aligned with those of the C-HPP. Our
      software has been able to highlight an intense expression of proteins previously
      known to be correlated with cancers (e.g., glutathione S-transferase Mu 3), and
      in particular, we draw attention to Gastrokine-2, a "missing protein" identified
      in this work of which we were able to clearly delineate the tumoral region from
      the "healthy" with our approach. Data are available via ProteomeXchange with
      identifier PXD000584. 

PMID- 24283987
TI  - Bilateral ocular anomalies in a South African fur seal (Arctocephalus pusillus
      pusillus).
AB  - A female South African fur seal (Arctocephalus pusillus pusillus) began having
      obvious clinical ophthalmologic problems by 8 weeks of age. The initial clinical
      sign was diffuse corneal edema, which progressed to bullae formation and ulcers;
      the underlying cause of corneal edema and bullous keratopathy was not identified
      antemortem.An ophthalmological evaluation was performed when the fur seal was
      approximately 6 months of age, but due to the diffuse corneal edema, intraocular
      structures could not be easily evaluated. An underlying infectious etiology was
      suspected; therefore,appropriate diagnostics were pursued, but did not identify a
      cause. Initial improvement was noted, but the fur seal then became blind and
      eventually became very painful.Due to decreased quality of life and aggressive
      behavior, the fur seal was euthanized.Histopathological diagnoses were persistent
      tunica vasculosa lentis and persistent hyperplastic primary vitreous with
      bilateral hypermature resorbed cataracts and retinal detachments with rosette
      formation.

PMID- 24283985
TI  - A SNP in the 5' flanking region of the myostatin-1b gene is associated with
      harvest traits in Atlantic salmon (Salmo salar).
AB  - BACKGROUND: Myostatin (MSTN) belongs to the transforming growth factor-beta
      superfamily and is a potent negative regulator of skeletal muscle development and
      growth in mammals. Most teleost fish possess two MSTN paralogues. However, as a
      consequence of a recent whole genome-duplication event, salmonids have four: MSTN
      1 (-1a and -1b) and MSTN-2 (-2a and -2b). Evidence suggests that teleost MSTN
      plays a role in the regulation of muscle growth. In the current study, the MSTN
      1b gene was re-sequenced and screened for SNP markers in a commercial population
      of Atlantic salmon. After genotyping 4,800 progeny for the discovered SNPs, we
      investigated their association with eight harvest traits - four body-weight
      traits, two ratios of weight traits, flesh colour and fat percentage - using a
      mixed model association analysis. RESULTS: Three novel SNPs were discovered in
      the MSTN-1b gene of Atlantic salmon. One of the SNPs, located within the 5'
      flanking region (g.1086C > T), had a significant association with harvest traits
      (p < 0.05), specifically for: Harvest Weight (kg), Gutted Weight (kg), Deheaded
      Weight (kg) and Fillet Weight (kg). The haplotype-based association analysis was
      consistent with this result because the two haplotypes that showed a significant
      association with body-weight traits, hap4 and hap5 (p < 0.05 and p < 0.01,
      respectively), differ by a single substitution at the g.1086C > T locus. The
      alleles at g.1086C > T act in an additive manner and explain a small percentage
      of the genetic variation of these phenotypes. CONCLUSIONS: The association
      analysis revealed that g.1086C > T had a significant association with all body
      weight traits under study. Although the SNP explains a small percentage of the
      variance, our results indicate that a variation in the 5' flanking region of the
      myostatin gene is associated with the genetic regulation of growth in Atlantic
      salmon.

PMID- 24283988
TI  - The need for a predictive, context-dependent approach to the application of
      stress hormones in conservation.

PMID- 24283989
TI  - SoxR as a single-cell biosensor for NADPH-consuming enzymes in Escherichia coli.
AB  - An ultra-high-throughput screening system for NADPH-dependent enzymes, such as
      stereospecific alcohol dehydrogenases, was established. It is based on the [2Fe
      2S] cluster-containing transcriptional regulator SoxR of Escherichia coli that
      activates expression of soxS in the oxidized but not in the reduced state of the
      cluster. As SoxR is kept in its reduced state by NADPH-dependent reductases, an
      increased NADPH demand of the cell counteracts SoxR reduction and increases soxS
      expression. We have taken advantage of these properties by placing the eyfp gene
      under the control of the soxS promoter and analyzed the response of E. coli cells
      expressing an NADPH-dependent alcohol dehydrogenase from Lactobacillus brevis
      (LbAdh), which reduces methyl acetoacetate to (R)-methyl 3-hydroxybutyrate. Under
      suitable conditions, the specific fluorescence of the cells correlated with the
      substrate concentration added and with LbAdh enzyme activity, supporting the
      NADPH responsiveness of the sensor. These properties enabled sorting of single
      cells harboring wild-type LbAdh from those with lowered or without LbAdh activity
      by fluorescence-activated cell sorting (FACS). In a proof-of-principle
      application, the system was used successfully to screen a mutant LbAdh library
      for variants showing improved activity with the substrate 4-methyl-2-pentanone. 

PMID- 24283991
TI  - Pruritic erythematous vesicles over the lower legs in a 36-year-old woman.

PMID- 24283990
TI  - Cytomegalovirus vaccine: phase II clinical trial results.
AB  - Cytomegalovirus (CMV) is one of the most significant viral pathogens during
      pregnancy and in immunocompromised patients. Antiviral prophylactic strategies
      are limited by toxicities, drug-drug interactions and development of antiviral
      resistance. A safe and protective vaccine against CMV is highly desirable in view
      of the potential positive impact on CMV-associated morbidity and mortality as
      well as healthcare costs. Unfortunately, this demand could not be met in the past
      four decades although development of a CMV vaccine has been ranked at the highest
      priority by the US Institute of Medicine. Multiple different vaccine candidates
      have been developed and evaluated in phase I clinical trials and few succeeded to
      phase II trials. Nevertheless, two different vaccines showed recently promising
      results in trials that studied healthy adults and immunocompromised solid-organ
      and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine
      exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant
      patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of
      viraemia and consequently the need for antiviral treatment. The success of these
      trials is encouraging and will probably give new impetus to the development of an
      effective CMV vaccine. Sterilizing immunity may not be attainable in the near
      future and may not be necessary for a CMV vaccine to have a significant impact on
      health care as discussed in the present review. 

PMID- 24283992
TI  - Time from diagnosis to surgery and prostate cancer survival: a retrospective
      cohort study.
AB  - BACKGROUND: A diagnosis of prostate cancer leads to emotional distress and
      anxiety, prompting calls for rapid diagnostic pathways. Nevertheless, it remains
      unclear what impact time between diagnosis and surgery has upon prostate cancer
      survival. METHODS: Using national databases for England (cancer registries,
      Hospital Episode Statistics and Office of National Statistics), we identified
      17,043 men with prostate cancer, aged 15 years and older, diagnosed in 1996-2009,
      and who had surgical resection with curative intent within 6 months of diagnosis.
      We used relative survival to investigate associations between waiting times and
      five- and ten-year survival. RESULTS: Five- and ten-year relative survival
      estimates for the total study sample were 1.04 (95% CI: 1.04 to 1.05) and 1.08
      (95% CI: 1.06-1.09), respectively. There were no notable differences in survival
      between patients who had surgery at 0-3 and 4-6 months after diagnosis. Relative
      survival was higher among the elderly (>65) and those with well and moderately
      differentiated tumours. CONCLUSION: The high relative survival in our cohort
      probably reflects adherence to selection criteria for surgery among men with
      localised prostate cancer. Among men treated with surgery within 6 months of
      diagnosis, we found little evidence of an association between time from diagnosis
      to surgery and survival.

PMID- 24283993
TI  - Stimuli-responsive chemomechanical actuation: a hybrid materials approach.
AB  - Dynamic materials that can sense changes in their surroundings and functionally
      respond by altering many of their physical characteristics are primed to be
      integral components of future "smart" technologies. A fundamental reason for the
      adaptability of biological organisms is their innate ability to convert
      environmental or chemical cues into mechanical motion and reconfiguration on both
      the molecular and macroscale. However, design and engineering of robust
      chemomechanical behavior in artificial materials has proven a challenge. Such
      systems can be quite complex and often require intricate coordination between
      both chemical and mechanical inputs and outputs, as well as the combination of
      multiple materials working cooperatively to achieve the proper functionality. It
      is critical to not only understand the fundamental behaviors of existing dynamic
      chemomechanical systems but also apply that knowledge and explore new avenues for
      design of novel materials platforms that could provide a basis for future
      adaptive technologies. In this Account, we explore the chemomechanical behavior,
      properties, and applications of hybrid-material surfaces consisting of
      environmentally sensitive hydrogels integrated within arrays of high-aspect-ratio
      nano- or microstructures. This bio-inspired approach, in which the volume
      changing hydrogel acts as the "muscle" that reversibly actuates the
      microstructured "bones", is highly tunable and customizable. Although
      straightforward in concept, the combination of just these two materials
      (structures and hydrogel) has given rise to a far more complex set of actuation
      mechanisms and behaviors. Variations in how the hydrogel is physically integrated
      within the structure array provide the basis for three fundamental mechanisms of
      actuation, each with its own set of responsive properties and chemomechanical
      behavior. Further control over how the chemical stimulus is applied to the
      surface, such as with microfluidics, allows for generation of more precise and
      varied patterns of actuation. We also discuss the possible applications of these
      hybrid surfaces for chemomechanical manipulation of reactions, including the
      generation of chemomechanical feedback loops. Comparing and contrasting these
      many approaches and techniques, we aim to put into perspective their highly
      tunable and diverse capabilities but also their future challenges and impacts. 

PMID- 24283994
TI  - Beyond our wildest dreams.

PMID- 24283995
TI  - Would the benefits of hexaminolevulinate fluorescence cystoscopy be eliminated if
      every patient received postoperative installation of intravesical chemotherapy?

PMID- 24283996
TI  - Histology core-specific evaluation of the European Society of Urogenital
      Radiology (ESUR) standardised scoring system of multiparametric magnetic
      resonance imaging (mpMRI) of the prostate.

PMID- 24283997
TI  - Diabetes mellitus and non-muscle-invasive bladder cancer: not just a coincidence?

PMID- 24283998
TI  - Minimally invasive surgical training: do we need new standards?

PMID- 24283999
TI  - Defining standardized but succinct outcomes for partial nephrectomy.

PMID- 24284000
TI  - Coming full circle.

PMID- 24284001
TI  - Letter: intravesical Bacille Calmette-Guerin (BCG) in immunologically compromised
      patients with bladder cancer--reply.

PMID- 24284003
TI  - Health related quality of life of children with rheumatic heart diseases:
      reliability of the Brazilian version of the Pediatric Quality of Life InventoryTM
      Cardiac Module scale.
AB  - BACKGROUND: This study aimed to translate the 'Pediatric Quality of Life
      InventoryTM (PedsQLTM 3.0) Cardiac Module' into Portuguese, adapt it to Brazilian
      culture, and assess its psychometric properties (validity and reproducibility),
      and to calculate health-related quality of life scores on the PedsQL 4.0 and
      PedsQLTM 3.0 Cardiac Module Scales for a group of patients 5 to 18 years old with
      rheumatic heart disease. METHODS: The methods suggested by the authors of the
      original version of the questionnaire included 1) translation by an expert panel;
      2) translation back into English and revision by the authors of the original
      version; 3) pilot study with seven children and parents in each of three age
      ranges (5 to 7, 8 to 12, and 13 to 18 years old); and 4) assessment of the
      measurement properties. In this stage, the PedsQLTM 3.0 Cardiac Module and the
      PedsQL 4.0 Generic Scale were applied to a sample comprising 109 children and
      adolescents with rheumatic heart disease and their parents or caregivers. The
      version for parents or caregivers was administered separately on the same day.
      RESULTS: The values of Cronbach's alpha for all scales assessed in the
      questionnaire (heart problems and treatment [symptoms], problems with perceived
      physical appearance, treatment anxiety, cognitive problems, and communication
      problems) varied from 0.6 to 0.8, indicating good internal consistency.
      Correlation was found between the scores for the Cardiac Module and the Generic
      Scale (0.36-0.86), demonstrating convergent validity (Spearman's correlation
      coefficient, p < 0.01). The symptoms, problems with perceived physical
      appearance, and cognitive and communication problem domains were able to
      distinguish between groups of patients with mild and moderate/severe heart
      disease (Student's t-test, p < 0.05). The intraclass correlation of the
      interobserver reproducibility was adequate (0.76 to 0.94 among the patients
      [children/adolescents] and 0.76 to 0.84 among their caregivers). The correlation
      between the patients' scores and their parents' scores varied from 0.50 to 0.86
      (Pearson's correlation coefficient, p < 0.01). CONCLUSIONS: The Brazilian version
      of the PedsQLTM 3.0 Cardiac Module was shown to be reliable. The application of
      this questionnaire in practice will be very useful for all professionals charged
      with the care of children and adolescents with heart diseases.

PMID- 24284002
TI  - Trial of repeated analgesia with Kangaroo Mother Care (TRAKC Trial).
AB  - BACKGROUND: Skin-to-skin contact (SSC) between mother and infant, commonly
      referred to as Kangaroo Mother Care (KMC), is recommended as an intervention for
      procedural pain. Evidence demonstrates its consistent efficacy in reducing pain
      for a single painful procedure. The purpose of this study is to examine the
      sustained efficacy of KMC, provided during all routine painful procedures for the
      duration of Neonatal Intensive Care Unit (NICU) hospitalization, in diminishing
      behavioral pain response in preterm neonates. The efficacy of KMC alone will be
      compared to standard care of 24% oral sucrose, as well as the combination of KMC
      and 24% oral sucrose. METHODS/DESIGN: Infants admitted to the NICU who are less
      than 36 6/7 weeks gestational age (according to early ultrasound), that are
      stable enough to be held in KMC, will be considered eligible (N = 258). Using a
      single-blinded randomized parallel group design, participants will be assigned to
      one of three possible interventions: 1) KMC, 2) combined KMC and sucrose, and 3)
      sucrose alone, when they undergo any routine painful procedure (heel lance,
      venipuncture, intravenous, oro/nasogastric insertion). The primary outcome is
      infant's pain intensity, which will be assessed using the Premature Infant Pain
      Profile (PIPP). The secondary outcome will be maturity of neurobehavioral
      functioning, as measured by the Neurobehavioral Assessment of the Preterm Infant
      (NAPI). Gestational age, cumulative exposure to KMC provided during non-pain
      contexts, and maternal cortisol levels will be considered in the analysis.
      Clinical feasibility will be accounted for from nurse and maternal
      questionnaires. DISCUSSION: This will be the first study to examine the repeated
      use of KMC for managing procedural pain in preterm neonates. It is also the first
      to compare KMC to sucrose, or the interventions in combination, across time.
      Based on the theoretical framework of the brain opioid theory of attachment, it
      is expected that KMC will be a preferred standard of care. However, current pain
      management guidelines are based on minimal data on repeated use of either
      intervention. Therefore, regardless of the outcomes of this study, results will
      have important implications for guidelines and practices related to management of
      procedural pain in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01561547.

PMID- 24284004
TI  - Lack of in vitro effect of aglepristone on IFN-gamma and IL-4 production by
      resting and mitogen-activated T cells of luteal bitches.
AB  - BACKGROUND: Aglepristone (RU534) is an antiprogestin used for pregnancy
      termination, parturition induction and conservative pyometra treatment in
      bitches. Its molecular structure is similar to mifepristone, an antiprogestin
      used in human medicine. Mifepristone has been shown to suppress proliferation and
      cytokine production by T cells, whereas the effect of aglepristone on T cell
      function remains elusive. The purpose of this project was to investigate the in
      vitro influence of RU534 on IFN-gamma and IL-4 synthesis by peripheral blood T
      cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral
      blood mononuclear cells (PBMCs) were incubated with three different dosages of
      aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The
      production of cytokines by resting or mitogen-activated T cells was determined by
      intercellular staining and flow cytometry analysis or ELISA assay, respectively.
      RESULTS: Our results showed no statistically significant differences in the
      percentage of IFN-gamma and IL-4-synthesizing CD4+ or CD8+ resting T cells
      between untreated and aglepristone-treated cells at 24 and 48 hours post
      treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar
      concentration of IFN-gamma and IL-4 in culture supernatants to those observed in
      mitogen-activated DMSO-treated PBMCs. Presented results indicate that
      administration of aglepristone for 48 hours has no influence on IFN-gamma and IL
      4 synthesis by resting and mitogen-activated T cells isolated from diestral
      bitches. CONCLUSIONS: We conclude that antiprogestins may differentially affect T
      cell function depending on the animal species in which they are applied.

PMID- 24284005
TI  - Consequences of different dietary energy sources during follicular development on
      subsequent fertility of cyclic gilts.
AB  - The objective of the present study was to investigate the effects of dietary
      induced insulin enhancement during the late luteal phase on subsequent fertility
      of gilts. Fifty-two littermate cyclic gilts were subjected to dietary treatments
      where two energy sources were tested: corn starch (T1) and soybean oil (T2). The
      experimental diets were supposed to provide similar amounts of dietary energy,
      but from different sources. Gilts were fed ad libitum, starting day 8 of the
      estrous cycle, until the next standing heat. Blood sampling was performed in a
      subgroup of 20 gilts on days 14 and 21 of the cycle for analyses of glucose and
      insulin, and after ovulation detection until 18 h after ovulation for
      progesterone. All gilts were slaughtered on day 28 of pregnancy and the
      reproductive tracts recovered for further analysis. T1 gilts showed higher
      postprandial insulin peak on days 14 and 21 and lower glucose levels 4 h after
      feeding on day 14 (P<0.05), however, there were no treatment effects on plasma
      progesterone concentrations. Dietary energy sources did not affect average daily
      feed intake, body weight and backfat on day 28 of pregnancy. Estrous cycle
      length, estrus duration and time of ovulation were not affected by previous
      nutritional treatments either. T1 gilts showed higher ovulation rates, number of
      embryos, embryo weight and placental weight (P<0.05). There were no treatment
      effects on pregnancy rate, embryo survival rate and volume of amniotic fluid. A
      positive correlation between progesterone concentration 18 h after ovulation and
      ovulation rate was observed (r=0.75; P<0.01). These results suggest that it is
      possible to manipulate dietary insulin response in cyclic gilts and, thus,
      improve reproductive efficiency when feeding starch as the main energy source
      during the late luteal and follicular phases of the cycle. 

PMID- 24284006
TI  - An explorative data-analysis to support the choice between hepatic resection and
      radiofrequency ablation in the treatment of hepatocellular carcinoma.
AB  - BACKGROUND: Whether to prefer hepatic resection or radiofrequency ablation as
      first line therapy for hepatocellular carcinoma is a matter of debate. AIMS: To
      compare outcomes of resection and ablation, in the treatment of early
      hepatocellular carcinoma, through a decision-making analysis. METHODS: Data of
      388 cirrhotic patients undergoing resection and of 207 undergoing radiofrequency
      ablation were reviewed. Two distinct regression models were devised and used to
      perform sensitivity and probabilistic analyses, to overcome biases of covariate
      distributions. RESULTS: Actuarial survival curves showed no difference between
      resection and ablation (P=0.270) despite the fact that ablated patients were
      older, with worse liver function and smaller, unifocal tumours (P<0.05),
      suggesting a complex, non-linear relationship between clinical, tumoral variables
      and treatments. Sensitivity and probabilistic analyses suggested that the
      superiority of resection over ablation decreased at higher Model for-End stage
      Liver Disease scores, and that ablation provided better results for smaller
      tumours and higher Model for-End stage Liver Disease scores. In patients with 2-3
      tumours up to 3 cm, the two treatments produced opposite comparative results in
      relation to the Model for-End stage Liver Disease score. CONCLUSIONS: The
      superiority, or the equivalence, of resection and ablation depends on the non
      linear relationship existing between treatment, tumour number, size and degree of
      liver dysfunction.

PMID- 24284008
TI  - The effect of the estrous cycle on the expression of prepro-orexin gene and
      protein and the levels of orexin A and B in the porcine pituitary.
AB  - Hypothalamic peptides orexin A (OXA) and orexin B (OXB) are derived from the
      proteolytic cleavage of a common precursor molecule, prepro-orexin (PPO). They
      act via two orexin receptors (OX1R and OX2R), which belong to the G-protein
      coupled receptor superfamily. Orexins are implicated in the regulation of arousal
      states, energy homeostasis and reproductive neuroendocrine function. The
      objective of this study was to investigate the presence and changes in orexin
      expression in the porcine pituitary during the estrous cycle. Adenohypophysis
      (AP) and neurohypophysis (NP) tissue samples were harvested on days 2 to 3, 10 to
      12, 14 to 16, and 17 to 19 of the estrous cycle. The expression of the PPO gene
      increased in AP and NP during the estrous cycle. The highest PPO protein
      concentrations in AP were reported on days 2 to 3 (P<0.05), and in NP - on days
      10 to 12 and 17 to 19 (P<0.05). The expression of PPO mRNA was lower in AP than
      in NP, but PPO protein levels were higher in AP. In AP, OXA immunoreactivity was
      higher (P<0.05) on days 10 to 12 and 14 to 16. In NP, the highest (P<0.05)
      content of the analyzed protein was observed on days 10 to 12 and the lowest
      (P<0.05) - on days 14 to 16 and 17 to 19. OXB immunoreactivity in AP reached the
      highest level (P<0.05) on days 2 to 3, and the lowest level (P<0.05) was
      determined on days 10 to 12 and 17 to 19. OXB protein concentrations in NP peaked
      (P<0.05) on days 10 to 12 of the cycle. Our study was the first experiment to
      demonstrate the expression of the orexin gene and orexin proteins in the porcine
      pituitary and the correlations between expression levels and the phase of the
      estrous cycle.

PMID- 24284007
TI  - Assessment of the new appropriate use criteria for diagnostic catheterization in
      the detection of coronary artery disease following noninvasive stress testing.
AB  - BACKGROUND: Appropriate use criteria (AUC) for diagnostic catheterization (DC)
      developed by the American College of Cardiology Foundation (ACCF) and other
      professional societies were recently published. These criteria have yet to be
      examined thoroughly using existing DC databases. METHODS AND RESULTS: New York
      State's Cardiac Diagnostic Catheterization Database was used to identify patients
      undergoing DC "for suspected coronary artery disease (CAD)" in 01/2010-06/2011
      who underwent noninvasive stress testing. Patients rated for appropriateness
      using symptoms and stress test results were examined to determine the percentage
      with obstructive CAD and to explore the benefit of adding Global Risk Score (GRS)
      to the AUC. Of the 4432 patients who could be rated, 1530 (34.5%) had obstructive
      CAD, which varied from 22% for patients rated inappropriate to 47% for patients
      rated appropriate. Of all patients with low risk stress test results/no symptoms,
      all of whom were rated "inappropriate" for DC, only 8% of those patients with low
      GRS had obstructive CAD, whereas 44% of the patients with high GRS had
      obstructive CAD. CONCLUSIONS: Global Risk Score improved the ability of symptoms
      and stress test results to identify obstructive CAD in patients with "suspected
      CAD" with prior stress tests, and it might be helpful to add GRS to the DC AUC
      for those patients. These findings should be regarded as hypothesis generating
      unless/until they can be confirmed by other data bases.

PMID- 24284009
TI  - Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation
      via Notch pathway activation.
AB  - Neural stem cell (NSC) transplantation for ischemic stroke is expected to repair
      the neuronal injury and replace the lost neurons through cell-cell cross talk
      between injured neurons and the transplanted NSCs. Here, we set up an in vitro co
      culturing system of oxygen-glucose deprivation (OGD) injured neurons and NSCs to
      investigate the neuronal repairing effect and effects on NSCs differentiation. We
      focused on the Notch1 pathway as a possible mediator of these effects. OGD
      injured neurons induced increased activation of Notch1 in co-cultured NSCs,
      through the up-regulations of the DLL1, the Notch1 intracellular domain (NICD)
      and the down-stream genes Hes1/5. When the NSCs were pre-treated with the Notch
      pathway inhibitor DAPT, the activation of Notch1 was blocked, lower NSCs
      differentiation was detected and the neurotrophic effect was also abolished. As
      shown by the novel co-culturing system, the NSCs co-cultured with OGD injured
      neurons were induced to differentiate through the Notch1 pathway activation; and
      these induced NSCs showed greater potential to support both the repair of injured
      neurons and form new neurons. 

PMID- 24284010
TI  - Hippocampal ether-a-go-go1 potassium channels blockade: effects in the startle
      reflex and prepulse inhibition.
AB  - Recently, our group described the ether-a-go-go1(Eag1) voltage-gated potassium
      (K(+)) channel (Kv10.1) expression in the dopaminergic cells indicating that
      these channels are part of the diversified group of ion channels related to
      dopaminergic neurons function. The increase of dopamine neurotransmission induces
      a reduction in the prepulse inhibition (PPI) of the acoustic startle reflex in
      rodents, which is a reliable index of sensorimotor gating deficits. The PPI
      response has been reported to be abnormally reduced in schizophrenia patients.
      The role of Eag1 K(+) channels in the PPI reaction had not been revealed until
      now, albeit the singular distribution of Eag1 in the dentate gyrus of the
      hippocampus and the hippocampal regulation of the startle reflex and PPI. The aim
      of this work was to investigate if Eag1 blockade on hippocampus modifies the PPI
      disruptive effects of apomorphine in Wistar rats. Bilateral injection of anti
      Eag1 single-chain antibody into the dentate gyrus of hippocampus did not modify
      apomorphine-disruptive effects in the PPI response. However, Eag1 antibody
      completely restored the startle amplitude decrease revealed after dentate gyrus
      surgery. These potentially biological important phenomenon merits further
      investigation regarding the role of Eag1 K(+) channels, mainly, on startle reflex
      modulation, since the physiological role of these channels remain obscure. 

PMID- 24284011
TI  - Urban gardening: managing the risks of contaminated soil.

PMID- 24284012
TI  - Interpreting bisphenol a absorption in the canine oral cavity: Gayrard et al.
      Respond.

PMID- 24284013
TI  - Giant mucocele originating from the middle concha in a 5-year-old child: a case
      report.
AB  - INTRODUCTION: Mucoceles are mucus-filled, epithelial-lined sacs that slowly
      develop in the paranasal sinuses when sinus or concha bullosa drainage is
      obstructed by inflammatory processes, trauma, or prior surgery. They are
      extremely rare in children. Symptoms usually arise from the nasal obstruction or
      compression of neighboring structures. CASE PRESENTATION: This case report
      describes a 5-year-old Turkish boy with a 3-year history of nasal obstruction. A
      computed tomography scan showed a well-defined soft tissue density lesion,
      seemingly originating in the region of the middle concha and was suggestive of a
      middle concha mucocele. The mass was removed by endoscopic sinus surgery.
      CONCLUSIONS: In the case of a child presenting with nasal obstruction, mucocele
      should be remembered in the differential diagnosis of intranasal tumors. Computed
      tomography and magnetic resonance imaging are helpful in making the diagnosis and
      endoscopic nasal surgery has proven successful in the treatment.

PMID- 24284014
TI  - Meeting the needs of the people: fish consumption rates in the Pacific Northwest.

PMID- 24284015
TI  - Measles epidemics of variable lethality in the early 20th century.
AB  - Until the mid-20th century, mortality rates were often very high during measles
      epidemics, particularly among previously isolated populations (e.g., islanders),
      refugees/internees who were forcibly crowded into camps, and military recruits.
      Searching for insights regarding measles mortality rates, we reviewed historical
      records of measles epidemics on the Polynesian island of Rotuma (in 1911), in
      Boer War concentration camps (in 1900-1902), and in US Army mobilization camps
      during the First World War (in 1917-1918). Records classified measles deaths by
      date and clinical causes; by demographic characteristics, family relationships
      (for Rotuma islanders and Boer camp internees), and prior residences; and by camp
      (for Boer internees and US Army recruits). During the Rotuman and Boer War
      epidemics, measles-related mortality rates were high (up to 40%); however,
      mortality rates differed more than 10-fold across camps/districts, even though
      conditions were similar. During measles epidemics, most deaths among camp
      internees/military recruits were due to secondary bacterial pneumonias; in
      contrast, most deaths among Rotuman islanders were due to gastrointestinal
      complications. The clinical expressions, courses, and outcomes of measles during
      first-contact epidemics differ from those during camp epidemics. The degree of
      isolation from respiratory pathogens other than measles may significantly
      determine measles-related mortality risk. 

PMID- 24284016
TI  - [Paediatric and Preventive Medicine Departments: together, better for resolving
      outbreaks].

PMID- 24284017
TI  - Association between cardiovascular events and sodium-containing effervescent,
      dispersible, and soluble drugs: nested case-control study.
AB  - OBJECTIVE: To determine whether patients taking formulations of drugs that
      contain sodium have a higher incidence of cardiovascular events compared with
      patients on non-sodium formulations of the same drugs. DESIGN: Nested case
      control study. SETTING: UK Primary Care Patients registered on the Clinical
      Practice Research Datalink (CPRD). PARTICIPANTS: All patients aged 18 or over who
      were prescribed at least two prescriptions of sodium-containing formulations or
      matched standard formulations of the same drug between January 1987 and December
      2010. MAIN OUTCOME MEASURES: Composite primary outcome of incident non-fatal
      myocardial infarction, incident non-fatal stroke, or vascular death. We performed
      1:1 incidence density sampling matched controls using the UK Clinical Practice
      Research Datalink (CPRD). For the secondary analyses, cases were patients with
      the individual components of the primary study composite endpoint of
      hypertension, incident heart failure, and all cause mortality. RESULTS: 1,292,337
      patients were included in the study cohort. Mean follow-up time was 7.23 years. A
      total of 61,072 patients with an incident cardiovascular event were matched with
      controls. For the primary endpoint of incident non-fatal myocardial infarction,
      incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure
      to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The
      adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for
      incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18
      (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94
      (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to
      1.59) for vascular death. The median time from date of first prescription (that
      is, date of entry into cohort) to first event was 3.92 years. CONCLUSIONS:
      Exposure to sodium-containing formulations of effervescent, dispersible, and
      soluble medicines was associated with significantly increased odds of adverse
      cardiovascular events compared with standard formulations of those same drugs.
      Sodium-containing formulations should be prescribed with caution only if the
      perceived benefits outweigh these risks.

PMID- 24284018
TI  - Reporting of results from animal studies.

PMID- 24284019
TI  - The use of the SeDeM diagram expert system for the formulation of Captopril SR
      matrix tablets by direct compression.
AB  - The SeDeM diagram expert system has been used to study excipients, Captopril and
      designed formulations for their galenic characterization and to ascertain the
      critical points of the formula affecting product quality to obtain suitable
      formulations of Captopril direct compression SR matrix tablets. The application
      of the SeDeM diagram expert system enables selecting excipients with in order to
      optimize the formula in the preformulation and formulation studies. The
      methodology is based on the implementation of ICH Q8, establishing the design
      space of the formula with the use of experiment design, using the parameters of
      the SeDeM diagram expert system as system responses. 

PMID- 24284020
TI  - Investigation of healthcare-acquired infections associated with Pseudomonas
      aeruginosa biofilms in taps in neonatal units in Northern Ireland.
AB  - BACKGROUND: In December 2011 and early 2012 four neonates died from Pseudomonas
      aeruginosa bacteraemia in hospitals in Northern Ireland. AIM: To assess whether
      P. aeruginosa was associated with the neonatal unit taps and whether waterborne
      isolates were consistent with patient isolates. METHODS: Thirty taps and eight
      flow straighteners from the relevant hospitals were categorized and dismantled
      into 494 components and assessed for aerobic colony and P. aeruginosa counts
      using non-selective and selective agars. P. aeruginosa isolates were typed by
      variable number tandem repeat (VNTR) analysis. Selected tap components were
      subjected to epifluorescence and scanning electron microscopy to visualize
      biofilm. FINDINGS: The highest P. aeruginosa counts were from the flow
      straighteners, metal support collars and the tap bodies surrounding these two
      components. Complex flow straighteners had a significantly higher P. aeruginosa
      count than other types of flow straighteners (P < 0.05). Highest aerobic colony
      counts were associated with integrated mixers and solenoids (P < 0.05), but there
      was not a strong correlation (r = 0.33) between the aerobic colony counts and P.
      aeruginosa counts. Representative P. aeruginosa tap isolates from two hospital
      neonatal units had VNTR profiles consistent with strains from the tap water and
      infected neonates. CONCLUSION: P. aeruginosa was predominantly found in biofilms
      in flow straighteners and associated components in the tap outlets and was a
      possible source of the infections observed. Healthcare providers should be aware
      that water outlets can be a source of P. aeruginosa contamination and should take
      steps to reduce such contamination, monitor it and have strategies to minimize
      risk to susceptible patients.

PMID- 24284021
TI  - PFOA and cancer in a highly exposed community: new findings from the C8 science
      panel.

PMID- 24284022
TI  - A new hope for patients suffering from multiple myeloma.
AB  - Multiple myeloma is a common hematological malignancy that leads to the
      occurrence of bone lesions. The combination of traditional cytotoxic and novel
      agents is usually taken to treat multiple myeloma-related bone diseases. However,
      the curative effect is not very satisfactory. Stem cell-based therapy has been
      recently introduced and investigated, which represents a new frontier in the
      treatment of multiple myeloma. In a recent interesting study, Dr Atsuta and
      colleagues provide a new insight into the effects of mesenchymal stem cells on
      multiple myeloma via Fas/Fas ligand pathway, which rekindles the fire of hope for
      those patients suffering from multiple myeloma.

PMID- 24284023
TI  - Influenza immunization coverage for healthcare workers in a community hospital in
      Qatar (2011-2012 and 2012-2013 seasons).
AB  - Influenza vaccination is recommended for all healthcare workers (HCW) to prevent
      transmission within healthcare facilities. We conducted a descriptive study on
      influenza vaccination coverage during 2011-2012 and 2012-2013 campaigns in a
      community hospital in Qatar. 61.7% of the HCW were immunized in the first
      campaign, with an increase of up to 71.1% (p<0.05) in the second one, which was
      mainly due to better compliance of doctors (46.9% and 69.2%, respectively). Our
      results show proper coverage rates according US standards and highlight the need
      to implement additional strategies to improve health workers adherence of
      influenza, vaccination.

PMID- 24284024
TI  - Epidemiological trends of tetanus from East Delhi, India: a hospital-based study.
AB  - OBJECTIVE: To study the demographic profile, prognostic indicators, and mortality
      of tetanus patients and treatment outcomes following intramuscular anti-tetanus
      immunoglobulin (ATG) alone or combined intrathecal and intramuscular ATG. DESIGN:
      Retrospective study. SETTING: Inpatients from a tertiary care hospital. SUBJECTS:
      One hundred children under 12 years of age diagnosed with tetanus and admitted
      from January 2003 to December 2007 were included in the study. METHODS: Case
      records of patients with neonatal tetanus (n=30) and post-neonatal tetanus (n=70)
      were evaluated retrospectively. The diagnosis of tetanus was based on World
      Health Organization (WHO) criteria. The outcomes of patients treated with either
      intramuscular ATG or both intrathecal and intramuscular ATG were separately
      compared in the neonatal and post-neonatal groups. RESULTS: Our study revealed
      difficulty in feeding, trismus, spasms, rigidity, and opisthotonus posturing as
      the predominant clinical manifestations. The survival rate for children receiving
      tetanus immunoglobulin by the dual route was significantly higher than for
      children receiving the immunoglobulin via the intramuscular route. Seizures and
      tremors were poor prognostic factors associated with tetanus.

PMID- 24284025
TI  - Prognostic effect of high-sensitive troponin T assessment in elderly patients
      with chronic heart failure: results from the CORONA trial.
AB  - BACKGROUND: The incremental prognostic value of high-sensitive troponin T (hs
      cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein
      and amino-terminal probrain natriuretic peptide is debated. We examined the
      prognostic value of hs-cTnT in a subgroup of patients from the Controlled
      Rosuvastatin Multinational Trial in HF (CORONA) study. METHODS AND RESULTS: Hs
      cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal
      myocardial infarction, and nonfatal stroke; n=356), as well as all-cause
      mortality (n=366), cardiovascular mortality (n=299), and the composite of
      cardiovascular mortality and hospitalization from worsening of HF (n=465), was
      investigated in 1245 patients (>=60 years; New York Heart Association [NYHA]
      class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or
      placebo. In multivariable analyses, adjusting for left ventricular ejection
      fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent
      claudication, heart rate, estimated glomerular filtration rate, apolipoprotein
      B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high
      sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the
      99th percentile and as a continuous variable) was associated with all end points
      (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change;
      P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved
      discrimination as assessed by C-statistics was only seen for the primary end
      point and all-cause mortality. CONCLUSIONS: Elevated hs-cTnT levels provide
      strong and independent prognostic information in older patients with chronic
      ischemic HF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00206310.

PMID- 24284026
TI  - Delta-6-desaturase links polyunsaturated fatty acid metabolism with phospholipid
      remodeling and disease progression in heart failure.
AB  - BACKGROUND: Remodeling of myocardial phospholipids has been reported in various
      forms of heart failure for decades, but the mechanism and pathophysiological
      relevance of this phenomenon have remained unclear. We examined the hypothesis
      that delta-6 desaturase (D6D), the rate-limiting enzyme in long-chain
      polyunsaturated fatty acid biosynthesis, mediates the signature pattern of fatty
      acid redistribution observed in myocardial phospholipids after chronic pressure
      overload and explored plausible links between this process and disease
      pathogenesis. METHODS AND RESULTS: Compositional analysis of phospholipids from
      hearts explanted from patients with dilated cardiomyopathy revealed elevated
      polyunsaturated fatty acid product/precursor ratios reflective of D6D
      hyperactivity, manifesting primarily as lower levels of linoleic acid with
      reciprocally higher levels of arachidonic and docosahexaenoic acids. This pattern
      of remodeling was attenuated in failing hearts chronically unloaded with a left
      ventricular assist device. Chronic inhibition of D6D in vivo reversed similar
      patterns of myocardial polyunsaturated fatty acid redistribution in rat models of
      pressure overload and hypertensive heart disease and significantly attenuated
      cardiac hypertrophy, fibrosis, and contractile dysfunction in both models. D6D
      inhibition also attenuated myocardial elevations in pathogenic eicosanoid
      species, lipid peroxidation, and extracellular receptor kinase 1/2 activation;
      normalized cardiolipin composition in mitochondria; reduced circulating levels of
      inflammatory cytokines; and elicited model-specific effects on cardiac
      mitochondrial respiratory efficiency, nuclear factor kappa B activation, and
      caspase activities. CONCLUSIONS: These studies demonstrate a pivotal role of
      essential fatty acid metabolism in myocardial phospholipid remodeling induced by
      hemodynamic stress and reveal novel links between this phenomenon and the
      propagation of multiple pathogenic systems involved in maladaptive cardiac
      remodeling and contractile dysfunction [corrected].

PMID- 24284027
TI  - In Support of EHP's Proposal to Adopt the ARRIVE Guidelines.

PMID- 24284028
TI  - Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a
      prospective, comparative, observational study.
AB  - OBJECTIVE: To evaluate pregnancy safety of anti-TNF-alpha medications. DESIGN:
      Prospective, comparative, observational study done at the Israeli Teratology
      Information Service between 2002 and 2011. RESULTS: 83 anti-TNF-alpha-exposed
      pregnancies (97.6% in the first trimester, T1) were followed-up and compared with
      86 disease-matched (DM) and 341 non-teratogenic-exposed (NTE) pregnancies. The
      anti-TNF-alpha group consisted of 35 infliximab-, 25 etanercept-, and 23
      adalimumab-exposed pregnancies. The rate of major congenital anomalies did not
      significantly differ between the three groups [3/65 (4.6%) (anti-TNF-alpha, T1),
      5/79 (6.3%) (DM), 8/336 (2.4%) (NTE)], even after excluding genetic or
      cytogenetic anomalies [3/65 (4.6%) (anti-TNF-alpha, T1), 4/79 (5.1%) (DM), 6/336
      (1.8%) (NTE)]. There were no cases of VATER/VACTERL association. CONCLUSION: The
      present study suggests that anti-TNF-alpha treatment does not pose a major
      teratogenic risk in humans. This conclusion is based on relatively small numbers
      of exposed pregnancies and should be interpreted with caution. Larger studies are
      needed to establish anti-TNF-alpha pregnancy safety.

PMID- 24284029
TI  - Small changes, big impact: exposure to air pollution and reduced lung function in
      children.

PMID- 24284030
TI  - The one and the many: effects of the cell adhesion molecule pathway on
      neuropsychological function in psychosis.
AB  - BACKGROUND: Genetic studies of single gene variants have been criticized as
      providing a simplistic characterization of the genetic basis of illness risk that
      ignores the effects of other variants within the same biological pathways. Of
      candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule
      (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive
      dysfunction. Here we tested, using risk allele scores derived from the
      Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ),
      whether alleles within the CAM pathway were correlated with poorer
      neuropsychological function in patients. METHOD: In total, 424 patients with
      psychosis were assessed in areas of cognitive ability typically found to be
      impaired in SZ: intelligence quotient, memory, working memory and attentional
      control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes
      and Genomes (KEGG) database. Alleles within these genes identified as
      significantly associated with SZ risk in the PGC-SCZ were then used to calculate
      a CAM pathway-based polygenic risk allele score for each patient and these scores
      were tested for association with cognitive ability. RESULTS: Increased CAM
      pathway polygenic risk scores were significantly associated with poorer
      performance on measures of memory and attention, explaining 1-3% of variation on
      these measures. Notably, the most strongly associated single nucleotide
      polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a
      similar amount of variance in attentional control, but not memory, as the
      polygenic risk analysis. CONCLUSIONS: These data support a role for the CAM
      pathway in cognitive function, both at the level of individual SNPs and the wider
      pathway. In so doing these data highlight the value of pathway-based polygenic
      risk score studies as well as single gene studies for understanding SZ-associated
      deficits in cognition.

PMID- 24284031
TI  - Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells.
AB  - Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics,
      resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are
      due to stimulated insulin release by the inhibition of the KATP channel activity
      of the beta cell. Recently, it was found that fluoroquinolones were much less
      effective on metabolically intact beta cells than on open cell preparations. Thus
      the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were
      investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial
      membrane potential, and the adenine nucleotide content of isolated pancreatic
      islets and beta cells. 100 MUM of moxifloxacin abolished the NAD(P)H increase
      elicited by 20mM glucose, while gatifloxacin diminished it and ciprofloxacin had
      no significant effect. This pattern was also seen with islets from SUR1 Ko mice,
      which have no functional KATP channels. Moxifloxacin also diminished the glucose
      induced decrease of FAD-fluorescence, which reflects the intramitochondrial
      production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or
      gatifloxacin significantly reduced the effect of 20mM glucose on the ATP/ADP
      ratio. The mitochondrial hyperpolarization caused by 20mM glucose was partially
      antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin.
      Ultrastructural analyses after 20 h tissue culture showed that all three
      compounds (at 10 and 100 MUM) diminished the number of insulin secretory granules
      and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced
      fission/fusion configurations of the beta cell mitochondria. In conclusion,
      fluoroquinolones affect the function of the mitochondria in pancreatic beta cells
      which may diminish the insulinotropic effect of KATP channel closure and
      contribute to the hyperglycaemic episodes.

PMID- 24284032
TI  - [Description of the clinical complexity of patients admitted to long term care
      hospitals in Catalonia during 2003-2009].
AB  - INTRODUCTION: This work describes the clinical complexity of patients admitted to
      long term care hospitals between 2003 and 2009. MATERIAL AND METHODS: Cross
      sectional analysis of Minimum Basic Dataset for Social and Healthcare Units
      information system data for 47,855 admissions. Outcomes assessed were functional
      and cognitive status, Resource Utilization Groups III (RUG-III), resource use
      categories, coverage and intensity of therapies, diagnosis, comorbidities, and
      medical procedures. Descriptive analyses were performed by year of admission.
      RESULTS: Dementia and acute cerebrovascular disease were the most frequent
      primary diagnoses, and showed a steady decline over time (8.8% and 2.3% decline),
      while family respite admissions and fractures increased (7.7% and 1.9%,
      respectively). The average functional and cognitive status of the treated
      population was similar across all years, although individuals with dependence in
      each Activity of Daily Living increased. The most frequent resource use
      categories were rehabilitation, reduced physical function, clinically complex
      care, and special care. A sharp increase in rehabilitation was observed during
      the study period (20.3%), while the other categories decreased. Increasingly more
      patients received rehabilitation therapy during their hospital stay (20.8%).
      Coverage increased particularly for physiotherapy (25.4%) and occupational
      therapy (17.4%). CONCLUSION: The clinical complexity faced by long term care
      hospitals increased during 2003- 2009. The use of resources and provision of
      therapies show an increasing rehabilitation effort, possibly as a response to
      changes in the clinical complexity of the treated population, the standards of
      care, or the established information reporting practices.

PMID- 24284033
TI  - [Kidney transplant in patients over 60 years-old in a Colombian hospital].
AB  - INTRODUCTION: Kidney transplantation is the treatment of choice in patients with
      end- stage renal disease. Renal transplantation in without fear of ethical
      conflicts is the best treatment option in the elderly. The objective is to
      describe the demographic and clinical characteristics of patients over 60 years
      old with at least one year of renal transplantation in a single center of
      Colombia. METHODS: This is a cohort study of patients over 60 years old from a
      single center in Bogota, Colombia. About 28 patients were analyzed between June
      2004 and March 2012. RESULTS: The mean age was 65 years old, with 89% males. The
      main cause of chronic kidney disease was diabetic nephropathy, followed by
      hypertensive nephrosclerosis. Most of them (96.4%) were deceased donor
      transplants with a mean age of 40 years old, cold ischemia time was 12 hours and
      there was a mismatch of 3.25 (+/- 1.29). Major comorbidities were hypertension,
      diabetes, dyslipidemia, and coronary arterial disease. Almost 17% had delayed
      graft dysfunction. Serum creatinine at 6 and 12 months was 1.27 mg/dl (+/- 0.31)
      and 1.25mg/dl (+/- 0.33), respectively. Only 10% of patients had acute cellular
      rejection. Humoral rejections were not documented. The patient survival at 1 year
      was 89.7%, and death-censored graft survival was 96.4%. The most frequent cause
      of death was acute myocardial infarction. CONCLUSIONS: Proper selection of kidney
      transplant recipients shows satisfactory results in survival, with low morbidity
      in patients older than 60 years.

PMID- 24284034
TI  - EHP Paper of the Year, 2013.

PMID- 24284035
TI  - Before the tremor: premotor symptoms of Parkinson's disease.

PMID- 24284036
TI  - Hyperoxia-induced developmental plasticity of the hypoxic ventilatory response in
      neonatal rats: contributions of glutamate-dependent and PDGF-dependent
      mechanisms.
AB  - Rats reared in hyperoxia exhibit a sustained (vs. biphasic) hypoxic ventilatory
      response (HVR) at an earlier age than untreated, Control rats. Given the
      similarity between the sustained HVR obtained after chronic exposure to
      developmental hyperoxia and the mature HVR, it was hypothesized that hyperoxia
      induced plasticity and normal maturation share common mechanisms such as enhanced
      glutamate and nitric oxide signaling and diminished platelet-derived growth
      factor (PDGF) signaling. Rats reared in 21% O2 (Control) or 60% O2 (Hyperoxia)
      from birth until 4-5 days of age were studied after intraperitoneal injection of
      drugs targeting these pathways. Hyperoxia rats receiving saline showed a
      sustained HVR to 12% O2, but blockade of NMDA glutamate receptors (MK-801)
      restored the biphasic HVR typical of newborn rats. Blockade of PDGF-beta
      receptors (imatinib) had no effect on the pattern of the HVR in Hyperoxia rats,
      although it attenuated ventilatory depression during the late phase of the HVR in
      Control rats. Neither nitric oxide synthase inhibitor used in this study (nNOS
      inhibitor I and l-NAME) altered the pattern of the HVR in Control or Hyperoxia
      rats. Drug-induced changes in the biphasic HVR were not correlated with changes
      in metabolic rate. Collectively, these results suggest that developmental
      hyperoxia hastens the transition from a biphasic to sustained HVR by upregulating
      glutamate-dependent mechanisms and downregulating PDGF-dependent mechanisms,
      similar to the changes underlying normal postnatal maturation of the biphasic
      HVR. 

PMID- 24284038
TI  - Modelled evaluation of multi-component meningococcal vaccine (Bexsero(r)) for the
      prevention of invasive meningococcal disease in infants and adolescents in the
      UK.
AB  - Neisseria meningitidis is the main cause of bacterial meningitis and sepsis in
      the UK, and can potentially be lethal or cause long-term sequelae. Bexsero(r)
      (4CMenB) is a new multi-component vaccine approved by the European Commission for
      use in individuals aged ?2 months. A theoretical transmission model was
      constructed to assess the long-term effectiveness of Bexsero compared to standard
      care. The model was populated with UK-specific demographic data and calibrated to
      ensure that the transmission dynamics of meningococcal disease in the UK were
      adequately simulated. The model showed the best strategy to be a routine
      vaccination programme at ages 2, 3, 4, 12 months and 14 years combined with a 5
      year catch-up programme in toddlers aged 12-24 months and adolescents aged 15-18
      years. This would lead to a 94% reduction in meningococcal cases or 150 000 cases
      and 15 000 deaths over a 100-year time-frame.

PMID- 24284039
TI  - Thalidomide distinctly affected TNF-alpha, IL-6 and MMP secretion by an ovarian
      cancer cell line (SKOV-3) and primary ovarian cancer cells.
AB  - BACKGROUND: Thalidomide inhibits TNF-alpha production in lipopolysaccharide
      stimulated monocytes. The aim of this study was to evaluate the effect of
      thalidomide on TNF-alpha, IL-6 and MMP secretion in epithelial ovarian carcinoma
      cells. MATERIALS AND METHODS: SKOV-3 cells and primary epithelial ovarian
      carcinoma cells were cultured in the presence of various concentrations of
      thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF
      alpha and IL-6 levels were determined in the supernatants of the cell cultures by
      ELISA, and MMP activity was examined by gelatin zymography. RESULTS: Thalidomide
      did not significantly affect the proliferation and growth of SKOV-3 cells.
      However, it decreased significantly the capacity of SKOV-3 cells and primary
      epithelial ovarian carcinoma cells to secrete TNF-alpha. Thalidomide also
      significantly decreased the capacity of SKOV-3 cells, but not primary epithelial
      ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not
      affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma
      cells. CONCLUSION: Our study suggests that thalidomide distinctly affected TNF
      alpha, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and
      primary ovarian cancer cells. This might suggest a different susceptibility of
      these two types of cells to thalidomide, and/or that the mechanisms of secretion
      of the factors examined are differently regulated in these cells. Our results may
      deepen our understanding the mechanism/s of action of thalidomide in ovarian
      carcinoma cells. The results might have important implications in future
      therapeutic strategies that will incorporate thalidomide and other cytokine
      inhibitors in the treatment of epithelial ovarian carcinoma.

PMID- 24284037
TI  - Role of central and peripheral opiate receptors in the effects of fentanyl on
      analgesia, ventilation and arterial blood-gas chemistry in conscious rats.
AB  - This study determined the effects of the peripherally restricted MU-opiate
      receptor (MU-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25MUg/kg,
      i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG)
      and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in
      conscious rats. The fentanyl-induced increase in analgesia was minimally affected
      by a 1.5mg/kg of NLXmi but was attenuated by a 5.0mg/kg dose. Fentanyl decreased
      arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These
      responses were markedly diminished in NLXmi (1.5mg/kg)-pretreated rats. Fentanyl
      caused ventilatory depression (e.g., decreases in tidal volume and peak
      inspiratory flow). Pretreatment with NLXmi (1.5mg/kg, i.v.) antagonized the
      fentanyl decrease in tidal volume but minimally affected the other responses.
      These findings suggest that (1) the analgesia and ventilatory depression caused
      by fentanyl involve peripheral MU-ORs and (2) NLXmi prevents the fentanyl effects
      on ABG by blocking the negative actions of the opioid on tidal volume and A-a
      gradient. 

PMID- 24284040
TI  - Downregualtion of dynamin-related protein 1 attenuates glutamate-induced
      excitotoxicity via regulating mitochondrial function in a calcium dependent
      manner in HT22 cells.
AB  - Glutamate-mediated excitotoxicity is involved in many acute and chronic brain
      diseases. Dynamin related protein 1 (Drp-1), one of the GTPase family of proteins
      that regulate mitochondrial fission and fusion balance, is associated with
      apoptotic cell death in cancer and neurodegenerative diseases. Here we
      investigated the effect of downregulating Drp-1 on glutamate excitotoxicity
      induced neuronal injury in HT22 cells. We found that downregulation of Drp-1 with
      specific small interfering RNA (siRNA) increased cell viability and inhibited
      lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of
      Drp-1 also inhibited an increase in the Bax/Bcl-2 ratio and cleavage of caspase-9
      and caspase-3. Drp-1 siRNA transfection preserved the mitochondrial membrane
      potential (MMP), reduced cytochrome c release, enhanced ATP production, and
      partly prevented mitochondrial swelling. In addition, Drp-1 knockdown attenuated
      glutamate-induced increases of cytoplasmic and mitochondrial Ca(2+), and
      preserved the mitochondrial Ca(2+) buffering capacity after excitotoxicity. Taken
      together, these results suggest that downregulation of Drp-1 protects HT22 cells
      against glutamate-induced excitatory damage, and this neuroprotection may be
      dependent at least in part on the preservation of mitochondrial function through
      regulating intracellular calcium homeostasis. 

PMID- 24284041
TI  - XPD gene polymorphisms and the effects of induction chemotherapy in
      cytogenetically normal de novo acute myeloid leukemia patients.
AB  - BACKGROUND: Cytogenetically normal acute myeloid leukemia (AML) represents nearly
      half of newly diagnosed de novo AML cases. XPD is one of the DNA repair proteins,
      whose genetic polymorphisms are thought to affect their function as regards
      response to chemotherapeutic drugs and chemotherapy-induced toxicities. SUBJECTS
      AND METHODS: We investigated the XPD Asp312Asn and Lys751Gln polymorphisms by
      polymerase chain reaction-restriction fragment length polymorphism in 51 newly
      diagnosed cytogenetically normal de novo AML patients. The response to the
      standard induction chemotherapy protocol and chemotherapy-induced toxicities were
      monitored. RESULTS: The XPD Asp312Asn GG genotype was the most frequent (57%)
      followed by the GA variant (37%), and the AA variant was the least frequent (6%).
      As regards the XPD Lys751Gln polymorphism, the AA genotype was the most frequent
      (49%), followed by the AC (39%) and CC (12%) variants. These variants were not
      associated with age, sex, FAB subtype, CNS infiltration, chemotherapy-induced
      hepatotoxicity, nephrotoxicity, or metabolic toxicity. The XPD Lys751Gln CC
      polymorphic variant was associated with chemotherapy-induced cardiotoxicity and
      lower chance to achieve response to induction chemotherapy. CONCLUSION: XPD
      Lys751Gln and not Asp312Asn polymorphism was associated with chemotherapy-induced
      cardiotoxicity and response to induction chemotherapy in newly diagnosed
      cytogenetically normal AML patients. Pretreatment assay of XPD Lys751Gln may help
      to anticipate cardiotoxicity in those at risk. Moreover, it may be considered a
      prognostic marker in AML cases. However, further large scale research is needed
      to verify its usefulness.

PMID- 24284043
TI  - Toxicity testing from the bottom up: proposed protocol for screening pollutants
      linked to insulin resistance.

PMID- 24284042
TI  - Exosomes neutralize synaptic-plasticity-disrupting activity of Abeta assemblies
      in vivo.
AB  - BACKGROUND: Exosomes, small extracellular vesicles of endosomal origin, have been
      suggested to be involved in both the metabolism and aggregation of Alzheimer's
      disease (AD)-associated amyloid beta-protein (Abeta). Despite their ubiquitous
      presence and the inclusion of components which can potentially interact with
      Abeta, the role of exosomes in regulating synaptic dysfunction induced by Abeta
      has not been explored. RESULTS: We here provide in vivo evidence that exosomes
      derived from N2a cells or human cerebrospinal fluid can abrogate the synaptic
      plasticity-disrupting activity of both synthetic and AD brain-derived Abeta.
      Mechanistically, this effect involves sequestration of synaptotoxic Abeta
      assemblies by exosomal surface proteins such as PrPC rather than Abeta
      proteolysis. CONCLUSIONS: These data suggest that exosomes can counteract the
      inhibitory action of Abeta, which contributes to perpetual capability for
      synaptic plasticity.

PMID- 24284044
TI  - R&D priorities in the field of sustainable remediation and purification of agro
      industrial and municipal wastewater.
AB  - This article was presented as a position paper during the Environmental
      Biotechnology and Microbiology Conference in Bologna, Italy in April 2012. It
      indicates major and emerging environmental biotechnology research and development
      (R&D) priorities for EU members in the field of sustainable remediation and
      purification of agro-industrial and municipal wastewater. The identified
      priorities are: anaerobic/aerobic microbial treatment, combination of
      photochemical and biological treatment, phytoremediation and algae-based
      remediation, as well as innovative technologies currently investigated, such as
      enzyme-based treatment, bioelectrochemical treatment and recovery of nutrients
      and reuse of cleaned water. State of the art, research needs and prospective
      development in these domains are crucially discussed. As a result, goals of the
      future development of bioremediation and purification processes are defined and
      the way to achieve them is proposed. 

PMID- 24284045
TI  - Biowaste biorefinery in Europe: opportunities and research & development needs.
AB  - This review aims to explore the needs and opportunities of research & development
      in the field of biowaste biorefinery in Europe. Modern industry in recent years
      is giving its close attention on organic waste as a new precious bioresource.
      Specific biowaste valorisation pathways are focusing on food processing waste,
      being food sector the first manufacture in Europe. Anyway they need to be further
      tested and validated and then transferred at the larger scale. In particular,
      they also need to become integrated, combining biomass pretreatments and recovery
      of biogenic chemicals with bioconversion processes in order to obtain a large
      class of chemicals. This will help to (a) use the whole biowaste, by avoiding
      producing residues and providing to the approach the required environmental
      sustainability, and (b) producing different biobased products that enter
      different markets, to get the possible economical sustainability of the whole
      biorefinery. However, the costs of the developed integrated processes might be
      high, mostly for the fact that the industry dealing with such issues is still
      underdeveloped and therefore dominated by high processing costs. Such costs can
      be significantly reduced by intensifying research & development on process
      integration and intensification. The low or no cost of starting material along
      with the environmental benefits coming from the concomitant biowaste disposal
      would offset the high capital costs for initiating such a biorefinery. As long as
      the oil prices tend to increase (and they will) this strategy will become even
      more attractive. 

PMID- 24284046
TI  - Risk factors associated with the presence of hepatitis E virus in livers and
      seroprevalence in slaughter-age pigs: a retrospective study of 90 swine farms in
      France.
AB  - The frequency of sporadic cases of hepatitis E in humans in developed countries
      has increased in recent years. The consumption of raw or undercooked pig liver
      based products has been identified as an important source of human infection. The
      question of possible massive human exposure to this zoonotic agent has been
      raised by the high prevalence of hepatitis E virus (HEV) in swine herds. However,
      little is known about the epidemiology of HEV on pig farms. A retrospective
      study, based on a previous prevalence study of 185 farms, was conducted on 90
      farms located in Western France, randomly selected from this database, to
      identify factors associated with the presence of HEV in pig livers and HEV
      seroprevalence in slaughter-age pigs. At least one HEV RNA-positive liver was
      found in 30% of the sampled farms while seroprevalence in slaughter-age pigs at
      the farm level reached almost 75%. Different factors were associated with the two
      conditions. The risk of having HEV-positive livers was increased by early
      slaughter, genetic background, lack of hygiene measures and surface origin of
      drinking water. High HEV seroprevalence was associated with mingling practices at
      the nursery stage and hygiene conditions. These results can be used to determine
      on-farm measures to reduce within-farm HEV spread and infection of slaughter-age
      pigs.

PMID- 24284047
TI  - Femoral radiographic landmarks for popliteus tendon reconstruction and repair: a
      new method of reference.
AB  - BACKGROUND: Although the popliteus muscle-tendon complex is one of the most
      important structures in controlling posterolateral rotatory stability of the
      knee, not much literature has been reported concerning the use of femoral
      radiographic landmarks of the popliteus tendon in repair and reconstruction.
      HYPOTHESIS: By using standardized radiographic techniques, the femoral insertion
      of the popliteus tendon could be more precisely determined by the Blumensaat line
      than by the extension line of the posterior cortex. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Ten fresh-frozen human knees were dissected, and the
      popliteus tendon was exposed. After identification of the femoral insertion site
      of the popliteus tendon, the insertion's center was indicated with a radiographic
      marker. True lateral radiographs of the distal femur were taken, and the digital
      radiographic images were analyzed by 2 independent observers. RESULTS: The
      femoral insertion site of the popliteus tendon was found to be a mean 47.5% +/-
      5.2% across the width of the femoral condyle, 60.7% +/- 7.8% along the
      perpendicular bisector of the Blumensaat line, 0.3 +/- 1.7 mm posterior to the
      extension line of the posterior femoral cortex, and 20.5 +/- 3.8 mm distal to the
      perpendicular line at the Blumensaat point. The variance from the mean point by
      using the Blumensaat line as a reference was significantly smaller than by using
      the extension line of the posterior cortex (mean, 2.6 vs 3.6 mm; P = .044).
      CONCLUSION: A reproducible anatomic and radiographic reference point for the
      femoral insertion of the popliteus tendon can be determined using standardized
      radiographic techniques and can be more precisely determined by the Blumensaat
      line compared with the extension line of the posterior femoral cortex. CLINICAL
      RELEVANCE: This radiographic information provides an adjunctive tool for
      preoperative, intraoperative, and postoperative assessments of surgical repair
      and reconstruction of the popliteus tendon.

PMID- 24284048
TI  - Preoperative femoral nerve block in hip arthroscopic surgery: a retrospective
      review of 108 consecutive cases.
AB  - BACKGROUND: The utility of a femoral nerve block as an adjunct for pain
      management has been recognized for various surgical techniques but has yet to be
      examined in the preoperative setting as an adjunct to general anesthesia for
      improved postoperative pain control in hip arthroscopic surgery. PURPOSE: To
      evaluate the safety and efficacy of a preoperative femoral nerve block for
      postoperative pain control in patients undergoing hip arthroscopic surgery. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective chart review
      of 108 consecutive hip arthroscopic surgery cases (in 103 patients) was carried
      out. All patients underwent arthroscopic surgery under a general anesthetic with
      or without a preoperative femoral nerve block. Groups were compared with respect
      to patient sex, age, and body mass index (BMI); physical status classification
      according to the American Society of Anesthesiologists (ASA); procedure
      performed; operative time; total intraoperative morphine-equivalent dose; pain
      scores (0-10 scale) recorded at 0, 15, 30, 45, and 60 minutes postoperatively in
      the post-anesthesia care unit (PACU); total morphine-equivalent dose in the PACU;
      presence of nausea or vomiting in the PACU; time to discharge from the PACU;
      oxycodone consumption in the surgical day care unit (SDCU); and maximal patient
      reported pain score in the SDCU. RESULTS: Twelve cases were excluded from the
      analysis for a total of 96 cases (in 92 patients). Forty patients had general
      anesthesia alone (group A), and 56 patients had a preoperative femoral nerve
      block before the induction of general anesthesia (group B). There was no
      significant difference between the groups with regard to sex, age, weight,
      height, BMI, ASA classification, or type of procedure performed. Patients who
      received a femoral nerve block also received a significantly lower total
      intraoperative morphine-equivalent dose than did those patients who did not
      receive a block. Postoperative patient-reported pain scores were lower at all
      time points for the femoral nerve block group; however, a statistical
      significance was seen only at the 60-minute postoperative time point. Patients
      who did not receive a block had significantly higher morphine-equivalent doses in
      the PACU. There was no difference in the rates of nausea and vomiting and time to
      discharge from the PACU between the 2 groups. Oxycodone consumption in the SDCU
      was similar between the groups, but the femoral nerve block group had
      significantly lower maximal patient-reported pain scores in the SDCU. Two
      patients in the general anesthesia group were admitted to the hospital
      postoperatively because of inadequate postoperative pain control. No
      complications were noted in any patient with regard to the femoral nerve block.
      CONCLUSION: A preoperative femoral nerve block is a relatively safe procedure
      that may decrease the requirement for intraoperative morphine while providing
      effective postoperative pain control in patients undergoing hip arthroscopic
      surgery.

PMID- 24284049
TI  - Complications after arthroscopic knee surgery.
AB  - BACKGROUND: Knee arthroscopies are among the most common procedures performed by
      orthopaedic surgeons, yet little is known about the associated complications and
      complication rates. PURPOSE: To examine the nature and frequency of complications
      after the most common arthroscopic knee procedures, with particular attention to
      fellowship training, geographic location of practice, and age and sex of the
      patient. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Data
      were obtained from the American Board of Orthopaedic Surgery database for
      orthopaedic surgeons who sat for the part II examination from 2003 to 2009. The
      database was queried to determine the type and frequency of complications for
      patients who underwent knee arthroscopy and for those who underwent sports
      medicine knee arthroscopy, including arthroscopic partial meniscectomy, meniscal
      repair, chondroplasty, microfracture, anterior cruciate ligament reconstruction,
      or posterior cruciate ligament reconstruction. Factors affecting complication
      rates that were investigated included type of procedure, fellowship training
      status, geographic location of practice, and age and sex of the patient. RESULTS:
      There were 4305 complications out of 92,565 knee arthroscopic procedures obtained
      from the American Board of Orthopaedic Surgery database for an overall candidate
      reported complication rate of 4.7%. The complication rates were highest for
      posterior cruciate ligament reconstruction (20.1%) and anterior cruciate ligament
      reconstruction (9.0%); complication rates for meniscectomy, meniscal repair, and
      chondroplasty were 2.8%, 7.6%, and 3.6%, respectively. The complication rate for
      sports fellowship-trained candidates was higher than for non-sports trained
      candidates (5.1% sports, 4.1% no sports; P < .0001) and for male patients (4.9%
      male vs 4.3% female; P < .0001). Younger patients (<40 years; 6.2%) had a higher
      complication rate than older patients (>=40 years; 3.58%) (P < .0001). Procedure
      complexity is a likely confounding factor affecting sports-trained candidates and
      younger patients. There were no geographic differences (P = .125). The overall
      rate of pulmonary embolus was 0.11%. Surgical complications (3.68%) were more
      common than medical (0.77%) or anesthetic complications (0.22%), and infection
      was the most common complication overall (0.84%). CONCLUSION: The overall self
      reported complication rate for arthroscopic knee procedures was 4.7%. Knee
      arthroscopy is not a benign procedure, and patients should be aware of the risk
      of complications.

PMID- 24284050
TI  - Anatomic, arthroscopically assisted, mini-open fibular collateral ligament
      reconstruction: an in vitro biomechanical study.
AB  - BACKGROUND: The fibular collateral ligament (FCL) is the primary restraint to
      varus rotation of the knee joint. Arthroscopic techniques are widely used and
      minimally invasive, but anatomic arthroscopic reconstruction of an isolated FCL
      injury has not been reported. HYPOTHESIS: Anatomic reconstruction of an isolated
      FCL injury can be performed arthroscopically and will restore the knee to near
      normal stability. STUDY DESIGN: Controlled laboratory study. METHODS: A total of
      12 nonpaired, fresh-frozen cadaveric knees were biomechanically subjected to a 10
      N.m varus moment and 5-N.m external and internal rotation torques at 0 degrees ,
      15 degrees , 30 degrees , 60 degrees , 90 degrees , and 120 degrees  of knee
      flexion, respectively (0 degrees  only for varus loading). Testing was performed
      with an intact and sectioned FCL and also after an anatomic reconstruction of the
      FCL by arthroscopic technique. Kinematics of each knee under various loading
      conditions was determined with a robotic universal force/moment sensor testing
      system. RESULTS: After sectioning, significant increases were found in varus
      rotation at 0 degrees , 15 degrees , 30 degrees , 60 degrees , 90 degrees , and
      120 degrees  of knee flexion; in external rotation at 15 degrees , 30 degrees ,
      and 60 degrees  of knee flexion; and in internal rotation at 30 degrees , 60
      degrees , and 90 degrees  of knee flexion. After reconstruction, full recovery of
      knee stability was observed in varus rotation at 0 degrees , 15 degrees , 30
      degrees , and 60 degrees ; in external rotation at 0 degrees , 15 degrees , 30
      degrees , 60 degrees , 90 degrees , and 120 degrees ; and in internal rotation at
      0 degrees , 15 degrees , 30 degrees , 60 degrees , 90 degrees , and 120 degrees .
      When the sectioned and intact FCL knee conditions were compared, significant
      increases of 3.4 degrees  at 90 degrees  of flexion and 3.4 degrees  at 120
      degrees  of flexion were found (P < .001, both conditions); when the
      reconstructed and sectioned FCL knee conditions were compared, significant
      decreases of 1.7 degrees  at 90 degrees  of flexion and 1.7 degrees  at 120
      degrees  of knee flexion were found (P = .033 and .043, respectively).
      CONCLUSION: An anatomic reconstruction of the FCL can be performed by an
      arthroscopically assisted mini-open technique with an isolated FCL injury, and
      near-normal stability of the knee can be restored. CLINICAL RELEVANCE: Anatomic
      reconstruction of the FCL by an arthroscopically assisted mini-open technique is
      a viable, less invasive option to treat nonrepairable isolated FCL injury.

PMID- 24284051
TI  - Doctors' health: taking the lifecycle approach.

PMID- 24284052
TI  - Excess winter deaths rose by 29% last year from 2011-12.

PMID- 24284053
TI  - Surgeon is struck off for repeatedly lying to patient over brain tumour removal.

PMID- 24284054
TI  - Sexual violence among children is widespread within gangs, report says.

PMID- 24284055
TI  - Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts
      chemoresistance in small cell lung cancer.
AB  - PURPOSE: Met receptor phosphorylation is associated with poor prognosis in human
      small cell lung cancer (SCLC). The aim of our work was to investigate the effects
      of hepatocyte growth factor (HGF)/Met-mediated epithelial-to-mesenchymal
      transition (EMT) in SCLC and to evaluate the role of Met inhibition in
      mesenchymal/chemorefractory SCLC models. EXPERIMENTAL DESIGN: SCLC models of HGF
      induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in
      BALB/c nude mice) for chemosensitivity and response to Met inhibition with PF
      2341066 (crizotinib). Human SCLC samples at diagnosis (N = 87) and relapse (N =
      5) were evaluated by immunohistochemistry and immunofluorescence for EMT markers
      and Met status and these were correlated with patient outcome. RESULTS: We
      identified that the activation of the Met receptor through HGF induced expression
      of mesenchymal markers, an aggressive phenotype, and chemoresistance. Blockade of
      this process with the Met inhibitor resensitized cells to chemotherapy in vitro
      and in vivo. Moreover, mesenchymal markers in human SCLC specimens were
      associated with Met activation, predicted worse survival, and were upregulated in
      chemorefractory disease. CONCLUSION: These results provide novel evidence on an
      important role of Met-dependent EMT in the adverse clinical behavior of SCLC and
      support clinical trials of Met inhibitors and chemotherapy in this fatal disease.

PMID- 24284056
TI  - Identification of a subset of human non-small cell lung cancer patients with high
      PI3Kbeta and low PTEN expression, more prevalent in squamous cell carcinoma.
AB  - PURPOSE: The phosphoinositide 3-kinase (PI3K) pathway is a major oncogenic
      signaling pathway and an attractive target for therapeutic intervention.
      Signaling through the PI3K pathway is moderated by the tumor suppressor PTEN,
      which is deficient or mutated in many human cancers. Molecular characterization
      of the PI3K signaling network has not been well defined in lung cancer; in
      particular, the role of PI3Kbeta and its relation to PTEN in non-small cell lung
      cancer NSCLC remain unclear. EXPERIMENTAL DESIGN: Antibodies directed against
      PI3Kbeta and PTEN were validated and used to examine, by immunohistochemistry,
      expression in 240 NSCLC resection tissues [tissue microarray (TMA) set 1].
      Preliminary observations were extended to an independent set of tissues (TMA set
      2) comprising 820 NSCLC patient samples analyzed in a separate laboratory
      applying the same validated antibodies and staining protocols. The staining
      intensities for PI3Kbeta and PTEN were explored and colocalization of these
      markers in individual tumor cores were correlated. RESULTS: PI3Kbeta expression
      was elevated significantly in squamous cell carcinomas (SCC) compared with
      adenocarcinomas. In contrast, PTEN loss was greater in SCC than in
      adenocarcinoma. Detailed correlative analyses of individual patient samples
      revealed a significantly greater proportion of SCC in TMA set 1 with higher
      PI3Kbeta and lower PTEN expression when compared with adenocarcinoma. These
      findings were reinforced following independent analyses of TMA set 2.
      CONCLUSIONS: We identify for the first time a subset of NSCLC more prevalent in
      SCC, with elevated expression of PI3Kbeta accompanied by a reduction/loss of
      PTEN, for whom selective PI3Kbeta inhibitors may be predicted to achieve greater
      clinical benefit.

PMID- 24284057
TI  - Cabozantinib and prostate cancer: inhibiting seed and disrupting soil?
AB  - Treatment with cabozantinib, an inhibitor of MET and VEGFR2 signaling, has
      demonstrated clinical benefit in early trials in men with metastatic prostate
      cancer. Preclinical evidence suggests that cabozantinib can kill cancer cell
      seeds while disrupting angiogenesis and stromal cells in the metastatic soil.

PMID- 24284059
TI  - Development of autobiographical memory in children with autism spectrum
      disorders: deficits, gains, and predictors of performance.
AB  - Autobiographical memory (AM) was assessed in 63 children (aged 8-17 years) with
      an autism spectrum disorder (ASD) and compared with 63 typically developing
      children matched for age, gender, IQ, and verbal ability. A range of
      methodologies was employed for eliciting past experience with particular focus on
      the ability to recall (a) specific events, (b) the recent and remote past, and
      (c) semantic versus episodic memories across different lifetime periods. Results
      indicated that the ASD group manifested difficulties in retrieving specific
      memories to word cues and had poorer access to the remote past. Deficits were
      found in the context of intact recent memory and preserved general memory
      abilities, with some impairment of visual memory. Problems in retrieving episodic
      and semantic AMs across the life span were also evident. Qualitative analysis of
      memory reports suggested that the ASD group was less likely to refer to emotion
      in their remote memories but more likely to describe emotions in their recent
      memories. Important predictors of AM performance in the ASD group were central
      executive abilities, in particular cognitive flexibility and verbal fluency. 

PMID- 24284058
TI  - A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia
      identifies novel potential disease markers and therapeutic targets.
AB  - PURPOSE: Despite new treatments, acute myeloid leukemia (AML) remains an
      incurable disease. More effective drug design requires an expanded view of the
      molecular complexity that underlies AML. Alternative splicing of RNA is used by
      normal cells to generate protein diversity. Growing evidence indicates that
      aberrant splicing of genes plays a key role in cancer. We investigated genome
      wide splicing abnormalities in AML and based on these abnormalities, we aimed to
      identify novel potential biomarkers and therapeutic targets. EXPERIMENTAL DESIGN:
      We used genome-wide alternative splicing screening to investigate alternative
      splicing abnormalities in two independent AML patient cohorts [Dana-Farber Cancer
      Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes,
      France)] and normal donors. Selected splicing events were confirmed through
      cloning and sequencing analysis, and than validated in 193 patients with AML.
      RESULTS: Our results show that approximately 29% of expressed genes genome-wide
      were differentially and recurrently spliced in patients with AML compared with
      normal donors bone marrow CD34(+) cells. Results were reproducible in two
      independent AML cohorts. In both cohorts, annotation analyses indicated similar
      proportions of differentially spliced genes encoding several oncogenes, tumor
      suppressor proteins, splicing factors, and heterogeneous-nuclear
      ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and
      spliceosome assembly. Our findings are consistent with reports for other
      malignances and indicate that AML-specific aberrations in splicing mechanisms are
      a hallmark of AML pathogenesis. CONCLUSIONS: Overall, our results suggest that
      aberrant splicing is a common characteristic for AML. Our findings also suggest
      that splice variant transcripts that are the result of splicing aberrations
      create novel disease markers and provide potential targets for small molecules or
      antibody therapeutics for this disease.

PMID- 24284060
TI  - Identification and validation of platelet low biological variation proteins,
      superior to GAPDH, actin and tubulin, as tools in clinical proteomics.
AB  - Accurate biomarker quantification requires carefully chosen normalisation
      procedures. When single proteins are used as loading controls (LCs), it is
      crucial that their expressional stability must be known. Platelets are an
      important biomarker source, especially for neurological diseases. We performed a
      systematical analysis of the platelet proteome to identify proteins suitable as
      LCs, using the 2-D DIGE system. We first screened a healthy population (n=137),
      aged between 18 and 104years, to find proteins with small coefficients of total
      variation (CVtot), herein termed low biological variation proteins (LBVP).
      Thereafter, expressional stability was verified in 101 patients suffering from
      Alzheimer's- (AD), Parkinson's- disease, vascular dementia or schizophrenia.
      Interestingly, traditional LCs such as tubulin beta-1 and GAPDH, were not found
      amongst LBVP. The least variable protein, calculated over all 238 individuals,
      was 14-3-3 gamma, with a CVtot of 9.3%, showing no gender, age or disease
      dependency. The normalisation capability of 14-3-3 gamma was superior to
      traditional LC in quantifying Western blot signals of the platelet AD-biomarker
      Monoamine Oxidase B of patient versus controls. Similar results were obtained
      with HepG2 cells, treated in vitro with DNA-methyltransferase inhibitor 5-aza
      2'deoxicytidine. Finally, we provide a list of alternative normalisation
      candidates for accurate biomarker quantification. BIOLOGICAL SIGNIFICANCE: This
      paper suggests a considerable list of platelet proteins with a lower biological
      variation than well known "housekeeping" proteins like GAPDH and tubulin. Spot
      abundances of found proteins are middle ranged and unaffected by gender, age and
      certain diseases. Hence, listed proteins might be valuable normalisation
      candidates used additionally or alternatively. Platelet's least variable protein
      14-3-3 gamma is validated as normalisation protein in platelet biomarker
      quantification. Furthermore 14-3-3 gamma is demonstrated to be also stable
      expressed by in HepG2, cells others than platelets, when treated by DNA
      methylation inhibitor.

PMID- 24284061
TI  - The effects of preference for information on consumers' online health information
      search behavior.
AB  - BACKGROUND: Preference for information is a personality trait that affects
      people's tendency to seek information in health-related situations. Prior studies
      have focused primarily on investigating its impact on patient-provider
      communication and on the implications for designing information interventions
      that prepare patients for medical procedures. Few studies have examined its
      impact on general consumers' interactions with Web-based search engines for
      health information or the implications for designing more effective health
      information search systems. OBJECTIVE: This study intends to fill this gap by
      investigating the impact of preference for information on the search behavior of
      general consumers seeking health information, their perceptions of search tasks
      (representing information needs), and user experience with search systems.
      METHODS: Forty general consumers who had previously searched for health
      information online participated in the study in our usability lab. Preference for
      information was measured using Miller's Monitor-Blunter Style Scale (MBSS) and
      the Krantz Health Opinion Survey-Information Scale (KHOS-I). Each participant
      completed four simulated health information search tasks: two look-up (fact
      finding) and two exploratory. Their behaviors while interacting with the search
      systems were automatically logged and ratings of their perceptions of tasks and
      user experience with the systems were collected using Likert-scale
      questionnaires. RESULTS: The MBSS showed low reliability with the participants
      (Monitoring subscale: Cronbach alpha=.53; Blunting subscale: Cronbach alpha=.35).
      Thus, no further analyses were performed based on the scale. KHOS-I had
      sufficient reliability (Cronbach alpha=.77). Participants were classified into
      low- and high-preference groups based on their KHOS-I scores. The high-preference
      group submitted significantly shorter queries when completing the look-up tasks
      (P=.02). The high-preference group made a significantly higher percentage of
      parallel movements in query reformulation than did the low-preference group
      (P=.04), whereas the low-preference group made a significantly higher percentage
      of new concept movements than the high-preference group when completing the
      exploratory tasks (P=.01). The high-preference group found the exploratory tasks
      to be significantly more difficult (P=.05) and the systems to be less useful
      (P=.04) than did the low-preference group. CONCLUSIONS: Preference for
      information has an impact on the search behavior of general consumers seeking
      health information. Those with a high preference were more likely to use more
      general queries when searching for specific factual information and to develop
      more complex mental representations of health concerns of an exploratory nature
      and try different combinations of concepts to explore these concerns. High
      preference users were also more demanding on the system. Health information
      search systems should be tailored to fit individuals' information preferences.

PMID- 24284062
TI  - Adipose-derived stem cells combined with beta-tricalcium phosphate: a novel
      possible strategy for periodontal defects regeneration.
AB  - Regeneration of destroyed periodontal tissue is a complicated problem in
      periodontal therapy. Conventional strategies such as surgical techniques,
      occlusive barrier membranes, and bone grafts have disadvantages that limit their
      application. Tissue engineering is a novel approach to regenerate periodontal
      tissue overcoming limitations of current strategies. In recent studies,
      researchers reported the potential of adipose-derived stem cells (ADSCs) to use
      in periodontal tissue regeneration. Unfortunately, in vivo studies indicated that
      small amount of alveolar bone formed using ADSCs implantation in the periodontal
      defects, which would be overcome by inducing osteogenic differentiation of ADSCs
      using osteoinductive biomaterials combined with ADSCs. Beta-tricalcium phosphate
      (beta-TCP) is an osteoinductive material which reported to induce osteogenic
      differentiation of adipose-derived stem cells. Based on the performed studies, we
      hypothesize that ADSCs from Wistar rat are isolated, induced by appropriate
      signaling molecules, seeded by beta-TCP, and then the complex was implanted into
      the periodontal defects in the same Wistar rat to observe the regeneration of
      periodontal tissue in vivo. This study will explore the possibility and
      application of ADSCs/beta-TCP complex for reconstructing periodontal defects. We
      believe it is especially useful to future clinical study and application in this
      field. 

PMID- 24284063
TI  - Pathological wave dynamics: a postulate for sudden cardiac death in athletes.
AB  - Sudden death (SD) in young athletes is a shocking and disturbing event with
      significant societal impact. Previous studies have demonstrated that sudden
      cardiac death (SCD) is the leading medical cause of SD in athletes. Various
      structural and pathological cardiovascular abnormalities have identified as the
      underlying causes of SCD in young athletes. However, there have been reported
      cases of SCD in athletes with no structural or pathological cardiovascular
      disorders. Our proposed hypothesis in this article is that abnormalities in
      aortic wave dynamics and coronary wave dynamics may be responsible for SCD in
      these athletes. These abnormal waves-pathological waves-can act as a trigger
      toward cardiac death in the presence of cardiovascular diseases. These waves may
      initiate SCD in the absence of apparent cardiovascular abnormalities. In summary,
      when the aortic and coronary wave dynamics are abnormal, the myocardial oxygen
      demand can exceed the oxygen delivery during exercise, hence creating acute
      ischemia which leads to death. It is explained in this article how increased
      oxygen demand may be the result of pathological aortic waves while reduced oxygen
      delivery is mainly due to pathological coronary waves. Additionally, our
      pathological wave hypothesis is able to provide a plausible explanation for
      Commotio Cordis.

PMID- 24284064
TI  - Biomachine dreams.

PMID- 24284066
TI  - Live cell imaging reveals actin-cytoskeleton-induced self-association of the
      actin-bundling protein WLIM1.
AB  - Crosslinking of actin filaments into bundles is essential for the assembly and
      stabilization of specific cytoskeletal structures. However, relatively little is
      known about the molecular mechanisms underlying actin bundle formation. The two
      LIM-domain-containing proteins define a novel and evolutionarily conserved family
      of actin-bundling proteins whose actin-binding and -crosslinking activities
      primarily rely on their LIM domains. Using TIRF microscopy, we describe real-time
      formation of actin bundles induced by tobacco NtWLIM1 in vitro. We show that
      NtWLIM1 binds to single filaments and subsequently promotes their interaction and
      zippering into tight bundles of mixed polarity. NtWLIM1-induced bundles grew by
      both elongation of internal filaments and addition of preformed fragments at
      their extremities. Importantly, these data are highly consistent with the modes
      of bundle formation and growth observed in transgenic Arabidopsis plants
      expressing a GFP-fused Arabidopsis AtWLIM1 protein. Using two complementary live
      cell imaging approaches, a close relationship between NtWLIM1 subcellular
      localization and self-association was established. Indeed, both BiFC and FLIM
      FRET data revealed that, although unstable NtWLIM1 complexes can sporadically
      form in the cytosol, stable complexes concentrate along the actin cytoskeleton.
      Remarkably, disruption of the actin cytoskeleton significantly impaired self
      association of NtWLIM1. In addition, biochemical analyses support the idea that F
      actin facilitates the switch of purified recombinant NtWLIM1 from a monomeric to
      a di- or oligomeric state. On the basis of our data, we propose a model in which
      actin binding promotes the formation and stabilization of NtWLIM1 complexes,
      which in turn might drive the crosslinking of actin filaments. 

PMID- 24284065
TI  - Frs2alpha and Shp2 signal independently of Gab to mediate FGF signaling in lens
      development.
AB  - Fibroblast growth factor (FGF) signaling requires a plethora of adaptor proteins
      to elicit downstream responses, but the functional significances of these docking
      proteins remain controversial. In this study, we used lens development as a model
      to investigate Frs2alpha and its structurally related scaffolding proteins, Gab1
      and Gab2, in FGF signaling. We show that genetic ablation of Frs2alpha alone has
      a modest effect, but additional deletion of tyrosine phosphatase Shp2 causes a
      complete arrest of lens vesicle development. Biochemical evidence suggests that
      this Frs2alpha-Shp2 synergy reflects their epistatic relationship in the FGF
      signaling cascade, as opposed to compensatory or parallel functions of these two
      proteins. Genetic interaction experiments further demonstrate that direct binding
      of Shp2 to Frs2alpha is necessary for activation of ERK signaling, whereas
      constitutive activation of either Shp2 or Kras signaling can compensate for the
      absence of Frs2alpha in lens development. By contrast, knockout of Gab1 and Gab2
      failed to disrupt FGF signaling in vitro and lens development in vivo. These
      results establish the Frs2alpha-Shp2 complex as the key mediator of FGF signaling
      in lens development. 

PMID- 24284067
TI  - Single-cell imaging of the heat-shock response in colon cancer cells suggests
      that magnitude and length rather than time of onset determines resistance to
      apoptosis.
AB  - Targeting the proteasome is a valuable approach for cancer therapy, potentially
      limited by pro-survival pathways that are induced in parallel to cell death.
      Whether these pro-survival pathways are activated in all cells, show different
      activation kinetics in sensitive versus resistant cells or interact functionally
      with cell death pathways is unknown. We monitored activation of the heat-shock
      response (HSR), a key survival pathway induced by proteasome inhibition, relative
      to apoptosis activation in HCT116 colon cancer cells expressing enhanced green
      fluorescent protein (EGFP) under the control of the HSP70 promoter. Single-cell
      and high-content time-lapse imaging of epoxomicin treatment revealed that neither
      basal activity nor the time of onset of the HSR differed between resistant and
      sensitive populations. However, resistant cells had significantly higher and
      prolonged reporter activity than those that succumbed to cell death. p53
      deficiency protected against cell death but failed to modulate the HSR. By
      contrast, inhibition of the HSR significantly increased the cytotoxicity of
      epoxomicin. Our data provide novel insights into the kinetics and heterogeneity
      of the HSR during proteasome inhibition, suggesting that the HSR modulates cell
      death signalling unidirectionally. 

PMID- 24284068
TI  - Slp2-a controls renal epithelial cell size through regulation of Rap-ezrin
      signaling independently of Rab27.
AB  - Synaptotagmin-like protein 2 (Slp2-a/Sytl2) is a Rab27 effector protein that
      regulates transport of Rab27-bearing vesicles and organelles through its N
      terminal Rab27-binding domain and a phospholipid-binding C2A domain. Here we
      demonstrate a Rab27-independent function of Slp2-a in the control of renal cell
      size through a previously uncharacterized C2B domain. We found that by recruiting
      Rap1 GAPs to the plasma membrane of MDCK II cells through the C2B domain, Slp2-a
      inactivates Rap signaling and modulates the size of the cells. Functional
      ablation of Slp2-a resulted in an increase in the size of MDCK II cells.
      Drosophila Slp Bitesize was found to compensate for the function of Slp2-a in
      MDCK II cells, thereby indicating that the mechanism of the cell size control by
      Slp proteins has been evolutionarily conserved. Interestingly, blockade of the
      activity of ezrin, a downstream target of Rap, with the glucosylceramide synthase
      inhibitor, miglustat, effectively inhibited cell spreading of Slp2-a-knockdown
      cells. We also discovered aberrant expression of Slp2-a and increased activity of
      ezrin in pcy (Nphp3(pcy)) mice, a model of polycystic kidney disease that is
      characterized by renal cell spreading. Our findings indicate that Slp2-a controls
      renal cell size through regulation of Rap-ezrin signaling independently of Rab27.

PMID- 24284070
TI  - Recurrent deletions of ULK4 in schizophrenia: a gene crucial for neuritogenesis
      and neuronal motility.
AB  - Although many pathogenic copy number variations (CNVs) are associated with
      neuropsychiatric diseases, few of them have been functionally characterised. Here
      we report multiple schizophrenia cases with CNV abnormalities specific to unc-51
      like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21
      34 of ULK4 were present in 4 out of 3391 schizophrenia patients from the
      International Schizophrenia Consortium, but absent in 3181 controls. Deletions
      removing exons 33 and 34 of the large splice variant of ULK4 also were enriched
      in Icelandic schizophrenia and bipolar patients compared with 98,022 controls (P
      = 0.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts
      gives a P-value less than 0.0001 for schizophrenia, or for schizophrenia plus
      bipolar disorder. The expression of ULK4 is neuron-specific and developmentally
      regulated. ULK4 modulates multiple signalling pathways that include ERK, p38, PKC
      and JNK, which are involved in stress responses and implicated in schizophrenia.
      Knockdown of ULK4 disrupts the composition of microtubules and compromises
      neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum
      agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene
      for schizophrenia.

PMID- 24284069
TI  - The molecular basis for selective assembly of the UBAP1-containing endosome
      specific ESCRT-I complex.
AB  - ESCRT-I is essential for the multivesicular body (MVB) sorting of ubiquitylated
      cargo such as epidermal growth factor receptor, as well as for several cellular
      functions, such as cell division and retroviral budding. ESCRT-I has four
      subunits; TSG101, VPS28, VPS37 and MVB12. There are several members of VPS37 and
      MVB12 families in mammalian cells, and their differential incorporation into
      ESCRT-I could provide function-specific variants of the complex. However, it
      remains unclear whether these different forms of VPS37 and MVB12 combine randomly
      or generate selective pairings within ESCRT-I, and what the mechanistic basis for
      such pairing would be. Here, we show that the incorporation of two MVB12 members,
      UBAP1 and MVB12A, into ESCRT-I is highly selective with respect to their VPS37
      partners. We map the region mediating selective assembly of UBAP1-VPS37A to the
      core ESCRT-I-binding domain of VPS37A. In contrast, selective integration of
      UBAP1 requires both the minimal ESCRT-I-binding region and a neighbouring
      predicted helix. The biochemical specificity in ESCRT-I assembly is matched by
      functional specialisation as siRNA-mediated depletion of UBAP1, but not MVB12A
      and MVB12B, disrupts ubiquitin-dependent sorting at the MVB.

PMID- 24284071
TI  - PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell
      motility and Rho GTPase activity.
AB  - Tyrosine phosphorylation is implicated in regulating the adherens junction
      protein, p120 catenin (p120), however, the mechanisms are not well defined. Here,
      we show, using substrate trapping, that p120 is a direct target of the protein
      tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of
      PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120
      concomitant with its enhanced tyrosine phosphorylation and decreased association
      with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased
      motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate.
      Furthermore, p120 localization is enhanced at actin-rich protrusions and
      lamellipodia and has an increased association with the guanine nucleotide
      exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is
      enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain
      or DH domain mutant blocks cell motility. Analysis of point mutations identified
      tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST
      dephosphorylation. A Y335F mutant of p120 failed to induce the 'p120 phenotype',
      interact with VAV2, stimulate cell motility or activate Rac1. Together, these
      data suggest that PTP-PEST affects epithelial cell motility by controlling the
      distribution and phosphorylation of p120 and its availability to control Rho
      GTPase activity. 

PMID- 24284073
TI  - Cdc42 and the Rho GEF intersectin-1 collaborate with Nck to promote N-WASP
      dependent actin polymerisation.
AB  - Vaccinia virus enhances its cell-to-cell spread by inducing Arp2/3-dependent
      actin polymerisation. This process is initiated by Src- and Abl-mediated
      phosphorylation of the viral transmembrane protein A36, leading to recruitment of
      a signalling network consisting of Grb2, Nck, WIP and N-WASP. Nck is a potent
      activator of N-WASP-Arp2/3-dependent actin polymerisation. However, recent
      observations demonstrate that an interaction between Nck and N-WASP is not
      required for vaccinia actin tail formation. We found that Cdc42 cooperates with
      Nck to promote actin tail formation by stabilising N-WASP beneath the virus.
      Cdc42 activation is mediated by the Rho guanine-nucleotide-exchange factor (GEF)
      intersectin-1 (ITSN1), which is recruited to the virus prior to its actin-based
      motility. Moreover, Cdc42, ITSN1 and N-WASP function collaboratively in a feed
      forward loop to promote vaccinia-induced actin polymerisation. Outside the
      context of infection, we demonstrate that ITSN1 also functions together with
      Cdc42, Nck and N-WASP during phagocytosis mediated by the Fc gamma receptor. Our
      observations suggest that ITSN1 is an important general regulator of Cdc42-, Nck-
      and N-WASP-dependent actin polymerisation.

PMID- 24284072
TI  - Cullin 5 destabilizes Cas to inhibit Src-dependent cell transformation.
AB  - Phosphorylation-dependent protein ubiquitylation and degradation provides an
      irreversible mechanism to terminate protein kinase signaling. Here, we report
      that mammary epithelial cells require cullin-5-RING-E3-ubiquitin-ligase complexes
      (Cul5-CRLs) to prevent transformation by a Src-Cas signaling pathway. Removal of
      Cul5 stimulates growth-factor-independent growth and migration, membrane dynamics
      and colony dysmorphogenesis, which are all dependent on the endogenous tyrosine
      kinase Src. Src is activated in Cul5-deficient cells, but Src activation alone is
      not sufficient to cause transformation. We found that Cul5 and Src together
      stimulate degradation of the Src substrate p130Cas (Crk-associated substrate).
      Phosphorylation stimulates Cas binding to the Cul5-CRL adaptor protein SOCS6 and
      consequent proteasome-dependent degradation. Cas is necessary for the
      transformation of Cul5-deficient cells. Either knockdown of SOCS6 or use of a
      degradation-resistant Cas mutant stimulates membrane ruffling, but not other
      aspects of transformation. Our results show that endogenous Cul5 suppresses
      epithelial cell transformation by several pathways, including inhibition of Src
      Cas-induced ruffling through SOCS6. 

PMID- 24284075
TI  - Src-like-adaptor protein (SLAP) differentially regulates normal and oncogenic c
      Kit signaling.
AB  - The Src-like-adaptor protein (SLAP) is an adaptor protein sharing considerable
      structural homology with Src. SLAP is expressed in a variety of cells and
      regulates receptor tyrosine kinase signaling by direct association. In this
      report, we show that SLAP associates with both wild-type and oncogenic c-Kit (c
      Kit-D816V). The association involves the SLAP SH2 domain and receptor
      phosphotyrosine residues different from those mediating Src interaction.
      Association of SLAP triggers c-Kit ubiquitylation which, in turn, is followed by
      receptor degradation. Although SLAP depletion potentiates c-Kit downstream
      signaling by stabilizing the receptor, it remains non-functional in c-Kit-D816V
      signaling. Ligand-stimulated c-Kit or c-Kit-D816V did not alter membrane
      localization of SLAP. Interestingly oncogenic c-Kit-D816V, but not wild-type c
      Kit, phosphorylates SLAP on residues Y120, Y258 and Y273. Physical interaction
      between c-Kit-D816V and SLAP is mandatory for the phosphorylation to take place.
      Although tyrosine-phosphorylated SLAP does not affect c-Kit-D816V signaling,
      mutation of these tyrosine sites to phenylalanine can restore SLAP activity.
      Taken together the data demonstrate that SLAP negatively regulates wild-type c
      Kit signaling, but not its oncogenic counterpart, indicating a possible mechanism
      by which the oncogenic c-Kit bypasses the normal cellular negative feedback
      control.

PMID- 24284074
TI  - RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal
      development.
AB  - Cell polarization is essential for neuronal development in both the embryonic and
      postnatal brain. Here, using primary cultures, in vivo postnatal electroporation
      and conditional genetic ablation, we show that the Ras-like small GTPase RalA and
      its effector, the exocyst, regulate the morphology and polarized migration of
      neural progenitors derived from the subventricular zone, a major neurogenic niche
      in the postnatal brain. Active RalA promotes the direct binding between the
      exocyst subunit Exo84 and the PDZ domain of Par6 through a non-canonical PDZ
      binding motif. Blocking the Exo84-Par6 interaction impairs polarization in
      postnatal neural progenitors and cultured embryonic neurons. Our results provide
      the first in vivo characterization of RalA function in the mammalian brain and
      highlight a novel molecular mechanism for cell polarization. Given that the
      exocyst and the Par complex are conserved in many tissues, the functional
      significance of their interaction and its regulation by RalA are likely to be
      important in a wide range of polarization events.

PMID- 24284077
TI  - NHS hospitals must become completely smoke free, says NICE.

PMID- 24284076
TI  - Integrins promote cytokinesis through the RSK signaling axis.
AB  - Cytokinesis is the final stage in cell division. Although integrins can regulate
      cytokinesis, the mechanisms involved are not fully understood. In this study, we
      demonstrate that integrin-regulated ERK (extracellular signal-related kinase) and
      RSK (p90 ribosomal S6 kinase) signaling promotes successful cytokinesis.
      Inhibiting the activation of ERK and RSK in CHO cells by a mutation in the
      integrin beta1 cytoplasmic tail or with pharmacological inhibitors results in the
      accumulation of cells with midbodies and the formation of binucleated cells.
      Activation of ERK and RSK signaling by the expression of constitutively active
      RAF1 suppresses the mutant phenotype in a RSK-dependent manner. Constitutively
      active RSK2 also restores cytokinesis inhibited by the mutant integrin.
      Importantly, the regulatory role of the RSK pathway is not specific to CHO cells.
      MCF-10A human mammary epithelial cells and HPNE human pancreatic ductal
      epithelial cells exhibit a similar dependence on RSK for successful cytokinesis.
      In addition, depriving mitotic MCF10A cells of integrin-mediated adhesion by
      incubating them in suspension suppressed ERK and RSK activation and resulted in a
      failure of cytokinesis. Furthermore, inhibition of RSK or integrins within the 3D
      context of a developing salivary gland organ explant also leads to an
      accumulation of epithelial cells with midbodies, suggesting a similar defect in
      cytokinesis. Interestingly, neither ERK nor RSK regulates cytokinesis in human
      fibroblasts, suggesting cell-type specificity. Taken together, our results
      identify the integrin-RSK signaling axis as an important regulator of cytokinesis
      in epithelial cells. We propose that the proper interaction of cells with their
      microenvironment through integrins contributes to the maintenance of genomic
      stability by promoting the successful completion of cytokinesis. 

PMID- 24284078
TI  - Altered neurochemical metabolites in Alzheimer's disease patients with
      unawareness of deficits.
AB  - BACKGROUND: Unawareness of deficits is common and is associated with poor
      outcomes in Alzheimer's disease (AD); however, little is known about correlated
      neurobiochemical changes. METHODS: Proton magnetic resonance spectroscopy was
      used to examine neurobiochemical correlates of unawareness of deficits as
      assessed by the Dementia Deficit Scale in 36 patients with AD. Magnetic resonance
      spectroscopy spectra were acquired from the anterior cingulate area and right
      orbitofrontal area. Concentrations of N-acetyl-aspartate (NAA), total creatine,
      and other neurometabolites were calculated. RESULTS: Nineteen (52.8%)
      participants had relative unawareness of deficits. This condition was negatively
      correlated with NAA/creatine in the anterior cingulate area (beta = -0.36, p =
      0.025) and positively correlated with NAA/creatine in the right orbitofrontal
      area (beta = 0.41, p = 0.009) after controlling for dementia severity.
      CONCLUSIONS: These findings suggest unawareness of deficits in AD was associated
      with the altered neurochemical metabolites in the anterior cingulate area and
      right orbitofrontal area. However, the two areas might have opposite neuronal
      functions in unawareness of deficits.

PMID- 24284079
TI  - Injury causation in the great outdoors: A systems analysis of led outdoor
      activity injury incidents.
AB  - Despite calls for a systems approach to assessing and preventing injurious
      incidents within the led outdoor activity domain, applications of systems
      analysis frameworks to the analysis of incident data have been sparse. This
      article presents an analysis of 1014 led outdoor activity injury and near miss
      incidents whereby a systems-based risk management framework was used to classify
      the contributing factors involved across six levels of the led outdoor activity
      'system'. The analysis identified causal factors across all levels of the led
      outdoor activity system, demonstrating the framework's utility for accident
      analysis efforts in the led outdoor activity injury domain. In addition, issues
      associated with the current data collection framework that potentially limited
      the identification of contributing factors outside of the individuals, equipment,
      and environment involved were identified. In closing, the requirement for new and
      improved data systems to be underpinned by the systems philosophy and new models
      of led outdoor activity accident causation is discussed. 

PMID- 24284080
TI  - Smartphones as multimodal communication devices to facilitate clinical knowledge
      processes: randomized controlled trial.
AB  - BACKGROUND: Despite the widespread use and advancements of mobile technology that
      facilitate rich communication modes, there is little evidence demonstrating the
      value of smartphones for effective interclinician communication and knowledge
      processes. OBJECTIVE: The objective of this study was to determine the effects of
      different synchronous smartphone-based modes of communication, such as (1) speech
      only, (2) speech and images, and (3) speech, images, and image annotation (guided
      noticing) on the recall and transfer of visually and verbally represented medical
      knowledge. METHODS: The experiment was conducted from November 2011 to May 2012
      at the University Hospital Basel (Switzerland) with 42 medical students in a
      master's program. All participants analyzed a standardized case (a patient with a
      subcapital fracture of the fifth metacarpal bone) based on a radiological image,
      photographs of the hand, and textual descriptions, and were asked to consult a
      remote surgical specialist via a smartphone. Participants were randomly assigned
      to 3 experimental conditions/groups. In group 1, the specialist provided verbal
      explanations (speech only). In group 2, the specialist provided verbal
      explanations and displayed the radiological image and the photographs to the
      participants (speech and images). In group 3, the specialist provided verbal
      explanations, displayed the radiological image and the photographs, and annotated
      the radiological image by drawing structures/angle elements (speech, images, and
      image annotation). To assess knowledge recall, participants were asked to write
      brief summaries of the case (verbally represented knowledge) after the
      consultation and to re-analyze the diagnostic images (visually represented
      knowledge). To assess knowledge transfer, participants analyzed a similar case
      without specialist support. RESULTS: Data analysis by ANOVA found that
      participants in groups 2 and 3 (images used) evaluated the support provided by
      the specialist as significantly more positive than group 1, the speech-only group
      (group 1: mean 4.08, SD 0.90; group 2: mean 4.73, SD 0.59; group 3: mean 4.93, SD
      0.25; F2,39=6.76, P=.003; partial eta(2)=0.26, 1-beta=.90). However, significant
      positive effects on the recall and transfer of visually represented medical
      knowledge were only observed when the smartphone-based communication involved the
      combination of speech, images, and image annotation (group 3). There were no
      significant positive effects on the recall and transfer of visually represented
      knowledge between group 1 (speech only) and group 2 (speech and images). No
      significant differences were observed between the groups regarding verbally
      represented medical knowledge. CONCLUSIONS: The results show (1) the value of
      annotation functions for digital and mobile technology for interclinician
      communication and medical informatics, and (2) the use of guided noticing (the
      integration of speech, images, and image annotation) leads to significantly
      improved knowledge gains for visually represented knowledge. This is particularly
      valuable in situations involving complex visual subject matters, typical in
      clinical practice.

PMID- 24284081
TI  - Ventral stream sensitivity in "healthy" preterm-born adolescents: psychophysical
      and neuropsychological evaluation.
AB  - BACKGROUND: Deficits of motion processing have been reported in premature and
      very low birth-weight subjects during infancy, childhood and adolescence. Less is
      known about ventral stream functioning in preterms. AIM: The aim of this study is
      to investigate ventral stream functioning in a sample of "healthy" adolescents
      born preterm with normal outcome and without brain damage. STUDY DESIGN: We
      enrolled thirty preterm-born adolescents (mean age: 14.2years, mean gestational
      age 28.9weeks, mean birth weight 1097g), and 34 age-matched term-born controls
      (mean age: 14.5years). All subjects were administered a psychophysical test known
      as "Form Coherence Task" and a comprehensive standardized battery of
      neuropsychological tests suitable for investigating ventral stream functioning
      including Street Completion Test, Poppelreuter-Ghent Test and the first part of
      the Visual Object and Space Perception (VOSP) battery. Dorsal stream visual
      functioning was investigated by the second part of the VOSP. RESULTS: Preterm
      (PT) subjects showed the same results in all "ventral" tasks with respect to full
      term controls without any correlation to gestational age or birth weight. We
      found a significant negative correlation between Form Coherence Task and Letters
      Task (p=.014) and between Form Coherence and Silhouette Tasks (p=.017). No
      correlation was observed between Form Coherence Task and Street and Ghent Tests.
      A statistical difference was instead found between PTs and controls in two tasks
      of the VOSP battery that mostly involve the dorsal stream. CONCLUSIONS: Preterm
      birth per se (in absence of evident brain lesions) is not sufficient to
      compromise the development of ventral pathway.

PMID- 24284082
TI  - Oncologic photodynamic therapy: clinical strategies that modulate mechanisms of
      action.
AB  - Photodynamic therapy (PDT) is an elegant minimally invasive oncologic therapy.
      The clinical simplicity of photosensitizer (PS) drug application followed by
      appropriate illumination of target leading to the oxygen dependent tumor ablative
      Photodynamic Reaction (PDR) has gained this treatment worldwide acceptance. Yet
      the true potential of clinical PDT has not yet been achieved. This paper will
      review current mechanisms of action and treatment paradigms with critical
      commentary on means to potentially improve outcome using readily available
      clinical tools. 

PMID- 24284083
TI  - Veterinary photodynamic therapy: a review.
AB  - Whereas in human medicine photodynamic therapy represents a well-known and
      recognized treatment option for diverse indications, it is still little known and
      unfortunately not yet established treatment option for pets. Various
      photosensitizers and light sources have been used and clinical results have been
      published. The main indication is a frequently occurring skin tumor in cats: in
      situ carcinoma/squamous cell carcinoma, mainly found in not or only slightly
      pigmented areas of the head. For early stages of this tumor, promising results
      have been published, partly using new, selective drugs to decrease light
      sensitivity after systemic administration and to increase response rates. Other
      possible indications are urinary tract neoplasia of dogs and equine sarcoids, the
      latter representing very common tumors in horses where no effective treatment is
      known so far. This review article summarizes the role of photodynamic therapy in
      veterinary medicine. 

PMID- 24284084
TI  - Discovering the mechanisms of strain-dependent response of Staphylococcus aureus
      to photoinactivation: oxidative stress toleration, endogenous porphyrin level and
      strain's virulence.
AB  - BACKGROUND: Staphylococcus aureus is generally known to be susceptible to
      photoinactivation. However, the phenomenon of its strain-dependent response to
      photodynamic treatment has been reported. Moreover, the factors determining the
      emerging variation among strains according to photoinactivation remain unclear.
      METHODS: This work aimed to investigate any relevant correlation between
      bacterial toleration of oxidative stress, porphyrin level, photosensitizer uptake
      and strain's virulence of studied methicillin-susceptible and methicillin
      resistant S. aureus strains and their response to photodynamic inactivation
      (using protoporphyrin diarginate, toluidine blue O and 5-aminolevulinic acid).
      RESULTS: Obtained data let to demonstrate that studied factors have limited
      impact on strain response to PDI. However, we have shown that multicomponent
      sensitizing agent i.e. consisted of PPArg2, ALA and TBO would eliminate the S.
      aureus elevated resistance to photoinactivation and that both highly virulent and
      low virulent S. aureus strains could be easily eradicated with the use of PDI.
      Moreover, we have shown that photodynamic inactivation could decrease the
      virulence of S. aureus extracellular fraction. CONCLUSION: The mechanism
      underlying strain-dependent response to photoinactivation is complex and
      multifactorial nevertheless with the use of several sensitizing agents the
      elevated resistance to photodynamic treatment can be omitted.

PMID- 24284085
TI  - Comparison of intraoperative fluorescence and MRI image guided neuronavigation in
      malignant brain tumours, a prospective controlled study.
AB  - INTRODUCTION: MBT carry poor prognosis and more than 80% of MBT recur locally
      within 2 cm of the resection margin because of inadequate surgical removal. A
      number of techniques have been implemented in recent years to improve surgical
      removal of MBT with variable success. We examined two methods commonly used to
      resect MBT to establish which one offered the best chances of gross total
      removal; MRI guided technology and ALA-induced fluorescence. PATIENTS AND
      METHODS: Twenty consecutive patients diagnosed with MBT were included in this
      study. They were given 20mg ALA per kg body weight 3h before anaesthesia orally
      mixed in water. Surgery was planned using preoperative enhanced MPR age images.
      Surgery was executed using the Stealth Station image guidance system and ALA
      induced fluorescence microsurgical techniques. During surgery the intensity of
      fluorescence was graded into red, pink or blue. The intensity of fluorescence was
      also measured using pulsed 405 nm laser and a compact spectrometer using a touch
      probe directly placed on the tissue. The extent of tumour invasion was assessed
      intraoperatively using standard white light, blue light and spectroscopic
      measurements. Postoperative enhanced MRI was used to assess the extent of
      resection and the volume of residual tumour was measured. RESULTS: There were six
      newly diagnosed GBM, eight recurrent GBM, one oligodendroglioma (ODG) and five
      metastases (MET). On enhanced MRI, the mean diameter of new GBM, recurrent GBM,
      ODG and MET was 2.3 cm, 2.3 cm, 1.5 cm, and 2.3 cm respectively. Under the blue
      light, the mean diameter of new GBM, recurrent GBM, ODG and MET was 2.9 cm, 3 cm,
      1.5 cm and 2.3 cm respectively. The results of quantitative measurements of
      fluorescence ratios revealed that red fluorescence corresponded to 5.9-11.6
      (solid tumour on histology), and pink fluorescence measured 0.8-1.9 (infiltrating
      edge of tumour on histology). When we compared the maximum tumour diameter of GBM
      we found on average it was 10mm wider on spectroscopy compared to standard white
      light microscopy and 6mm wider than what the enhanced MRI demonstrated.
      CONCLUSIONS: Fluorescence technology revealed that GBMs are wider than the
      enhanced MRI had demonstrated, while MET enhanced MRI was similar in size to
      fluorescence. Furthermore, solid tumour can be identified intraoperatively and
      can be measured using fluorescence and spectroscopy techniques and it can be
      removed safely. Infiltrating tumour can also be identified intraoperatively using
      this technology and can be removed in non-eloquent areas to maximise surgical
      resection.

PMID- 24284086
TI  - Risk factors for developing oral 5-aminolevulinic acid-induced side effects in
      patients undergoing fluorescence guided resection.
AB  - Oral 5 aminolevulinic acid (5-ALA) is used to assist surgical resection of
      malignant tumours in the brain and other locations. Hypotension and alteration of
      liver functions have been reported as potential adverse effects. This study was
      designed to assess the incidence and contributing factors that cause 5-ALA
      induced side effects in a cohort of 90 patients. Hypotension occurred in 11% of
      patients irrespective of 5-ALA dose. The only contributing factor was the
      presence of cardiovascular disease and antihypertensive drug therapy with an odd
      ratio of 17.7. Liver function were disturbed in 2% in patients who received 20mg
      or less/kg body weight compared to 4% in those who received a dose of >20mg/kg 5
      ALA. The liver dysfunction was minor and was not clinically significant. We
      concluded that 5-ALA induced side effects were minimal and hypotension more
      likely to occur in patients receiving antihypertensive drug therapy. 

PMID- 24284087
TI  - Effect of sub-lethal photodynamic inactivation on the antibiotic susceptibility
      and biofilm formation of clinical Staphylococcus aureus isolates.
AB  - BACKGROUND: A promising approach to kill antibiotic-resistant bacteria uses light
      in combination with a photosensitizer to induce a phototoxic reaction. A major
      concern with the use of any non-antibiotic antimicrobial treatment is that
      exposure of bacteria to sub-lethal concentrations will lead to the development of
      resistance to antibiotics. This study aimed to determine the effect of sub-lethal
      photodynamic inactivation (PDI) on the antibiotic susceptibility and biofilm
      formation of clinical Staphylococcus aureus isolates. METHODS: Forty clinical S.
      aureus isolates were exposed to PDI with toluidine blue O (TBO) and methylene
      blue (MB). After exposure, susceptibility of surviving organisms to a range of
      antibiotics was determined and compared with the susceptibility of an untreated
      control. PDI experiments were done during three generations for assessment of
      biofilm formation, to determine if biofilm formation was affected by exposure to
      PDI. RESULTS: It was observed that the effect of sub-lethal PDI on the antibiotic
      sensitivity was strain-dependent. In general, exposure to sub-lethal MB/TBO-PDI
      increased resistance to erythromycin, amoxicillin-clavulanate and amikacin.
      Biofilm formation ability of studied clinical isolates increased after second sub
      lethal PDI regimen compared to that before PDI. CONCLUSION: S. aureus cells may
      develop resistance by growing in the presence of sub-lethal MB/TBO-PDI.

PMID- 24284088
TI  - Tumor-selective near-infrared photodynamic therapy with novel indocyanine green
      loaded nanocarrier delays paralysis in rats with spinal metastasis.
AB  - BACKGROUND: Although recent advances in surgery have improved the quality of life
      of patients with spinal metastasis, local recurrence is still relatively common.
      Therefore, there is an urgent need for new surgical treatment options for
      metastatic spinal cancer. We previously described a novel nanocarrier loaded with
      indocyanine green (ICG), ICG-lactosome which exhibits tumor selectivity and is a
      potential near-infrared (NIR) fluorescence imaging agent for the diagnosis of
      spinal metastasis. The purpose of this study was to investigate the therapeutic
      effects of tumor-selective photodynamic therapy (PDT) with ICG-lactosome and NIR
      light irradiation in a rat model of spinal metastasis. METHODS: Twenty-one
      Fischer 344 rats each with a single spinal metastasis in the L6 vertebral body
      were divided into 3 treatment groups: PDT with a low-concentration ICG-lactosome
      injection (6 rats), PDT with high-concentration ICG-lactosome injection (7 rats),
      and a group without ICG-lactosome injection (8 rats). All the animals received
      local NIR light irradiation with a total energy of 5 J (0.5 W for 10s). RESULTS:
      Both the PDT groups injected with ICG-lactosome showed delayed deterioration of
      hind-limb paralysis compared with the group without ICG-lactosome. CONCLUSION:
      This modified PDT procedure could be an effective local treatment for spinal
      metastasis.

PMID- 24284089
TI  - A surgical loupe system for observing protoporphyrin IX fluorescence in high
      grade gliomas after administering 5-aminolevulinic acid.
AB  - BACKGROUND: We recently developed a surgical loupe system for observing the
      fluorescence emitted by protoporphyrin IX (PpIX), a metabolite of 5
      aminolevulinic acid. METHODS: This system used a semiconductor laser as the
      excitation light source. A compact, transparent, and ultraviolet cut-off filter
      was mounted on an eyepiece lens, which did not require filter on-off
      manipulation. RESULTS: Good quality protoporphyrin IX fluorescence was acquired
      using the surgical loupe system during glioblastoma resection, which was nearly
      identical to that acquired by fluorescent microscopy. In addition, surgeons can
      perform ordinary surgical procedures using this surgical loupe system under white
      light. CONCLUSION: This surgical loupe system enables the detection of PpIX
      fluorescence during resection of high-grade glioma. Further evaluations of this
      system are required to determine the extent of surgical resection before its
      practical application.

PMID- 24284090
TI  - An in vitro study on the photosensitivity of 5-aminolevulinic acid conjugated
      gold nanoparticles.
AB  - BACKGROUND: In this study, the photosensitivity of 5-aminolevulinic acid (5-ALA)
      conjugated gold nanoparticles (conjugate) has been investigated on the MeL-Rm
      cell line. METHODS: After culture and proliferation of the Mel-Rm cell line, cell
      toxicity and the suitable cell incubation time of the conjugate were determined.
      Photosensitivity of the conjugate and free 5-ALA was then studied in optical
      doses of 20, 40, 60 and 80 J/cm(2) while light irradiation was applied by a He-Ne
      laser. RESULTS: A 4-h time interval was determined as the optimum incubation time
      for 5-ALA and the conjugate. PpIX induction into the cells showed a significant
      increase after incubation with the conjugate in comparison to 5-ALA alone. Also,
      the conjugate resulted in a two times higher cell death rate compared to free 5
      ALA. CONCLUSION: The conjugate can be used as an appropriate delivery agent for 5
      ALA and provide efficient cell destruction during PDT.

PMID- 24284091
TI  - Protoporphyrin fluorescence induced by methyl-ALA in skin healing.
AB  - BACKGROUND: Estimation of the time period that precedes an injury is critical in
      forensic medicine. However, there is no reliable method that can be used to
      evaluate the oldness of a lesion. The aim of this work is to develop a
      fluorimetric method that can be used to follow the aging process of lesions by
      applying methyl-ALA (MAL) on wounds and by quantifying protoporphyrin IX (PPIX)
      fluorescence during the healing process. We also aim to understand the changes in
      PPIX fluorescence by establishing a correlation with histological evaluations
      during the healing process. METHODS: Standardized linear wounds were made on the
      dorsum of 72 mice, which were divided in control (MAL -) and experimental (MAL +)
      groups. In vivo fluorescence spectra (FS) were collected from normal and wound
      skin sites of control and experimental groups, corresponding to four groups of FS
      spectra: (a) FS of skin wound after MAL (+/+); (b) FS of normal skin after MAL (
      /+); (c) FS of skin wound without MAL (+/-) and (d) FS of normal skin without MAL
      (-/-). Animals were monitored periodically for 3 months and euthanized. Tissue
      specimens were processed for histological analysis using design-based
      stereological methods. Serial cross-sections were analyzed to evaluate the
      organization of the dermis and epidermis, collagen deposition and cellular
      proliferation. RESULTS: FS of skin wound with MAL (+/+) showed an expressive
      intensity increase from the beginning of the experiment to the 34th day, with
      maximum fluorescence being observed on the ~ 11 th day after wounding. There was
      preferential PPIX accumulation in healing sites as compared to adjacent normal
      skin (+/-) in the early stage of healing. Histological findings allowed
      correlation of the fluorescence increase mainly with cell proliferation. The
      drastic decrease in the FS intensity observed in the end of the healing process
      was correlated with the decrease in the proliferation rate as well as with the
      presence of new extracellular fibrous materials. CONCLUSIONS: In the mice wound
      healing model tested here, it was possible to distinguish whether the injury was
      in early or advanced stages by using PPIX fluorescence induced by MAL. We
      conclude that this method is a promising approach to evaluate the age of skin
      wounding and we hope this work will stimulate human studies to allow this
      technique to become standardized in forensic medicine.

PMID- 24284092
TI  - The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based
      photodynamic action for prostate cancer.
AB  - BACKGROUND: The aim of this study was to clarify the mechanism of accumulation of
      5-aminolevulinic acid (ALA)-dependent protoporphyrin IX (PpIX), ALA-photodynamic
      therapy (PDT)-induced cell death and enhanced efficiency by a ferrochelatase
      inhibitor in prostate cancer PC-3 cells. METHODS: The accumulation of ALA-induced
      PpIX in PC-3 cells was observed by fluorescence microscopy and measured by flow
      cytometry analysis. The efficiency of ALA-PDT was analyzed by flow cytometry and
      assessed by cell death, caspase-3 activity and mitochondrial membrane potential.
      The ALA-PDT-promoting effects of ferrochelatase inhibitors, such as deferoxamine
      and NOC-18, were also analyzed. We confirmed the results obtained in vivo with an
      animal model using nude mice. RESULTS: ALA-induced PpIX accumulation increased in
      time- and ALA concentration-dependent manners. ALA-PDT decreased the levels of
      mitochondrial membrane potential, and induced cell death occurred by both
      apoptosis and necrosis. Inhibition of ferrochelatase by deferoxamine and NOC-18
      led to increase of PpIX accumulation and enhanced effect of ALA-PDT in PC-3
      cells. In vivo, the degeneration of tumor tissue by ALA-PDT was observed within a
      broader range and led to apoptosis and necrosis. CONCLUSION: This study
      demonstrated ALA-PDT induced PC-3 cell death by the mechanisms of both necrosis
      and apoptosis through a caspase-independent mitochondrial pathway. Inhibition of
      ferrochelatase enhanced these effects, suggesting that ferrochelatase played an
      important role in ALA-PDT. ALA-PDT could be a new modality for focal therapy of
      prostate cancer.

PMID- 24284093
TI  - Successful treatment of recalcitrant dissecting cellulitis of the scalp with ALA
      PDT: case report and literature review.
AB  - A case of refractory dissecting cellulitis of the scalp (DCS) in a forty-one-year
      old Chinese female patient was treated with a total of 6 sessions of topical ALA
      PDT at one week intervals. The patient tolerated and responded well to this new
      approach without any adverse events. This suggested that topical ALA-PDT could be
      an effective and safe alternative for DCS patients who were refractory to other
      conventional therapies. We also reviewed etiology, pathophysiology, natural
      history and treatment options for DCS. 

PMID- 24284094
TI  - Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of
      canine breast cancer cells.
AB  - Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related
      photosensitize for photodynamic therapy (PDT). There still remains unknown
      changes regarding the mitochondrial in canine breast cancer cells treated with
      HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on
      structure and dysfunction of mitochondrial in cancer cells. The experimental
      approach included an initial study on the uptake of HMME using microscopic
      observation of the HMME-treated cells, optimization of the PDT-induced cell death
      by the MTT assay. These cells were then treated with HMME and a He-Ne laser at
      the wavelength of 632.8 nm following our optimized condition. Examination of
      mitochondrial changes by observing the stained cells under light microscope,
      mitochjondrial membrane potential flow cytometry, measuring the Ca(2+), SOD/GSH
      activity, ATPase and MDA contents for the mitochondria functions. The kinetics of
      HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear
      distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8
      J/cm(2) laser irradiation was had the maximal impact on cell viability. This
      treatment resulted in structural changes in mitochondria that were accompanied
      with the loss of mitochjondrial membrane potential. As a result, HMME-PDT
      increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial
      SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of
      calcium, and decreased mitochondrial ATPase activity. The combination of these
      abnormalities led to accumulation of ROS in mitochondrial to high levels, which
      in turn contributed to HMME-PDT-induced damages of mitochondrial structure and
      mitochondrial dysfunction.

PMID- 24284095
TI  - Comparison of efficiency of photodynamic diagnostics with topical use of the 3%
      and 15% aminolevulinic acid in the detection of vulvar lesions.
AB  - The essence of the photodynamic diagnostic method is interaction between light
      and chemical compounds that form in reaction to light. In order to obtain
      fluorescence, tissue has to be exposed to energy in the form of light with the
      wavelength corresponding to the bandwidth of the photosensitizer absorption. The
      photodynamic method allows for the detection of even small lesions. This method
      facilitates the process of detecting vulvar cancer, especially in its early
      stages when it can develop on the foundation of overgrown epithelium. At that
      point the vulvoscopic image is difficult to interpret, in particular when
      multifocal growth occurs. OBJECTIVES: The objective of the study was evaluating
      the efficiency of the photodynamic method PDD (photodynamic diagnosis) in the
      detection of vulvar lesions when two concentrations of the photosensitizer were
      used (3%- and 15%-aminolevulinic acid), as well as evaluating the efficiency of
      this method when compared to the efficiency of vulvoscopy, against the result of
      histological examination. METHODS: Two concentrations of the 5-ALA cream
      (aminolevulinic acid) - 3% and 15% - were used in the PDD testing. The study
      group was divided into two subgroups A and B. In subgroup A the 15% eucerine
      based cream was used. In subgroup B the 3% ALA gel with and addition of 2% DSMO
      was used. The photosensitizer was applied to the vulva 4-6h before the
      examination. In order to obtain fluorescence, energy in the form of light whose
      wavelength was approximately 405 nm, and whose source was a SLED diode, was
      transmitted to vulvar tissue. The positive result of the exam was obtaining
      tissue fluorescence. All patients underwent vulvoscopy and a histological
      examination of tissue samples was performed in all cases. The efficiency of the
      photodynamic testing in subgroups A and B was compared with the efficiency of
      vulvoscopy, against the result of histological examination. Sensitivity,
      specificity, as well as positive and negative predictive values of the PDD
      examination and vulvoscopy in both subgroups, were evaluated. RESULTS: When the
      15% ALA was used in detecting vulvar lesions, the photodynamic diagnostics was
      characterized by sensitivity of 100%, specificity of 92%, positive predictive
      value of 80%, negative predictive value of 100%, and correlation with the
      histopathological examination of 93.9%. When the 3% ALA was used, we observed:
      sensitivity of 100%, specificity of 91.4%, positive predictive value of 78.5%,
      negative predictive value of 100%, and correlation with the histopathological
      examination of 93.4%. Differences in the two subgroups were not statistically
      significant. CONCLUSIONS: High correlation was observed between the accuracy of
      the photodynamic method of examining vulvar lesions and the accuracy of the
      histological examination, especially in cases of precancerous lesions and vulvar
      cancer. The photodynamic examination, when the 3%-ALA/2%DSMO is used, is
      characterized by a greater sensitivity, comparable specificity, as well as,
      comparable positive and negative prognostic values, in comparison to the
      vulvoscopic examination. The photodynamic method, when used with other diagnostic
      methods, facilitates performing the needle aspiration biopsy and allows for a
      greater precision of histological diagnoses. The pathological fluorescence
      obtained during the PDD examination gives information about the spread and
      multifocality of vulvar lesions, which can facilitate making presurgical
      decisions concerning the extensiveness of surgery. The photodynamic method, when
      the 3% ALA/2% DSMO is applied topically, is of comparable efficiency as the 15%
      ALA, in the detection of vulvar lesions. High safety of the photodynamic method
      was shown, both in terms of the topical application of the aminolevulinic acid
      and the subsequent use of light.

PMID- 24284096
TI  - Spectral detection of sickle cell anemia and thalassemia.
AB  - Sickle cell disease (SCD) and thalassemia (Thal) are the most common inherited,
      autosomal, recessive blood disorders which lead to complications such as
      vasoocclusion and splenomegaly. Patients who suffer from these diseases have poor
      quality of life and shorter life span. The most common techniques for detection
      of these diseases are complete blood cell count, followed by electrophoresis and
      high performance liquid chromatography. In this connection, the results of this
      paper indicate the potential of a new technique, based on spectral analysis of
      blood plasma and cellular components, to detect SCD and Thal with accuracy of 90%
      and above. To the best of our knowledge this would be the first report on
      spectral pathology of hemoglobinopathy. 

PMID- 24284097
TI  - Parameter-finding studies of photodynamic therapy for approval in Japan and the
      USA.
AB  - OBJECTIVE: The purpose of this study is to investigate methods of evaluating
      therapeutic parameters used in the premarket evaluation of photodynamic therapy
      (PDT) drugs that have previously been approved in Japan and the United States, in
      order to establish a methodology that allows optimization of the therapeutic
      parameters of PDT, and to analyze current issues. MATERIALS AND METHODS: We
      examined the details of premarket evaluation of drug dose, drug-light intervals,
      as well as wavelengths, power density, and energy density of illumination sources
      used for the PDT drugs that have been approved in Japan the United States.
      RESULTS: There was a tendency for optimal drug dose and light energy density to
      be assessed in clinical studies. Drug-light intervals were assessed in the United
      States in clinical studies, and in Japan only in non-clinical studies. For
      various drugs, drug-light intervals were assessed based on fluorescence. For most
      drugs, the wavelength at which the drug can be photo-activated was determined in
      non-clinical studies. We found only few examples regarding the optimization of
      light power density as compared to the other therapeutic parameters. CONCLUSIONS:
      Drug dose, drug-light interval, and light energy density are particularly
      important parameters with regard to the efficacy and safety of PDT drugs. In
      order to determine the optimal therapeutic parameters of PDT more effectively,
      appropriate clinical studies need to be designed. Also the use of biomedical
      engineering, such as fluorescence measurement, is effective for optimizing PDT
      therapeutic parameters. We believe that in the future there will be a greater
      number of regulatory science related studies like ours will lead to the further
      spread of PDT.

PMID- 24284098
TI  - Photodynamic therapeutic effect of indocyanine green entrapped in polymeric
      nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice.
AB  - BACKGROUND: Indocyanine green (ICG) is a promising photosensitive agent for
      photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric
      nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the
      aqueous stability of the entrapped ICG molecules. The study objective is to
      investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate.
      METHODS: Skin squamous cell carcinoma was induced in CD1 mice by
      dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)
      followed by a PDT protocol for four weeks. RESULTS: PDT using ICG-PEBBLE or ICG
      PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the
      inflammatory mediators tumor necrosis factor (TNF-alpha), nitric oxide (NO),
      cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator
      vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen
      (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were
      induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE
      Anti-EGFR. CONCLUSION: The present study indicated the effectiveness of PDT using
      ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size,
      apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to
      anti-EGFR was found to be more effective in inhibiting VEGF and in increasing
      caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT
      efficacy.

PMID- 24284099
TI  - Photosan-II loaded hollow silica nanoparticles: preparation and its effect in
      killing for QBC939 cells.
AB  - BACKGROUND: Nanoparticles have been explored recently as an efficient means to
      deliver photosensitizers for photodynamic therapy. However, it is largely unknown
      if polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) or other photosensitizers
      can be efficiently delivered by hollow silica nanoparticles (HSNP). METHODS:
      Polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) was loaded into hollow silica
      nanoparticles (HSNP) by one-step wet chemical-based synthetic route. Dynamic
      light scattering (DLS) and polydispersive index (PDI) were used for measurement
      of the particles size and size distribution. Transmission electron microscope and
      scanning electron microscopy were used for the microstructure, morphological and
      chemical composition analysis. Fourier transform infrared spectrometry spectra
      and fluorescence emission spectrum were obtained. The photobiological activity of
      the PS-loaded HSNP was evaluated on human cholangiocarcinoma QBC939 cells. The
      cellular viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by
      flow cytometry. RESULTS: DLS measurements showed that the size of the particles
      is in the range of 25-90 nm. PDI of the PS-loaded HSNP is 0.121 +/- 0.01,
      indicating that samples have excellent quality with narrow size distribution to
      monomodal systems. In MTT assay, PS-loaded HSNP and free PS of the same
      concentration killed about 95.3% +/- 2.0% and 55.7% +/- 1.9% of QBC939 cells,
      respectively. The flow cytometry demonstrated that the laser induced cell death
      with PS-loaded HSNP was much more severe than that of free PS (P<0.05).
      CONCLUSIONS: Photosan-II-loaded hollow silica nanoparticles not only can quickly
      deliver Photosan-II into cells but also can reach a more high concentration than
      free Photosan-II. HSNP is a desirable vehicle and the release system that shows
      promises for photodynamic therapy use, which not only improve the aqueous
      solubility, stability and transport efficiency of PS, but also increase its
      photodynamic efficacy compared to free PS.

PMID- 24284100
TI  - Conjunction of glutathione level, NAD(P)H/FAD redox status and hypericin content
      as a potential factor affecting colon cancer cell resistance to photodynamic
      therapy with hypericin.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a highly efficient approach for tumour
      therapy, though it also has its drawbacks, too. There are multiple mechanisms
      involved in cell death regulation that can be successfully targeted for
      improvement of PDT in particular cases. We assumed, however, that the potential
      to manage radical stress might be the primary factor responsible for resistance
      to hypericin-mediated PDT (HY-PDT). METHODS: We compared the sensitivity of six
      colon-derived cancer cell lines to HY-PDT at IC50 equitoxic doses acquired by
      formazan-based (MTT) assay. Intracellular hypericin content, cell
      survival/metabolic activity, caspase-3 activation/mitochondrial membrane
      potential dissipation, apoptosis, glutathione level, redox status
      (NAD(P)H/oxidized flavins ratio) and Western blot analyses of proteins relevant
      in apoptosis regulation were measured to demonstrate differences between tested
      cell lines. RESULTS: Analyses revealed a whole spectrum of responses from
      insignificant to high cytotoxicity, despite the MTT-based "equitoxicity". Further
      critical evaluation of multiple parameters linked to cell physiology and
      proteomics proved that intracellular hypericin content, glutathione level or
      redox status demonstrate partial but not direct correlation with resistance to HY
      PDT, when considered separately. However, their logical conjunction did copy the
      trend of cellular resistance. CONCLUSIONS: We may conclude that intracellular
      level of hypericin and glutathione together with redox state of the target cell
      represent a potential combination of parameters responsible for the primary
      cytotoxicity of HY-PDT. We also present evidence that cytotoxic assays, such as
      the MTT, should be accompanied with other tests of cell survival/cytotoxicity in
      order to avoid incorrect conclusions.

PMID- 24284101
TI  - Porphyrins as urinary biomarkers for bladder cancer after 5-aminolevulinic acid
      (ALA) administration: the potential of photodynamic screening for tumors.
AB  - BACKGROUND: Tumor biomarkers are commonly used for cancer screening and as
      indicators of treatment effects. We recently reported that urine porphyrin levels
      from tumor-bearing mice were elevated compared with those from normal mice after
      administration of 5-aminolevulinic acid (ALA). In the present study, we evaluated
      the use of urine samples from bladder cancer patients as tumor biomarkers.
      METHODS: ALA, 1.0 g, was orally administered to 66 bladder cancer patients and 20
      healthy adults. The urine concentrations of uroporphyrin I (UPI), uroporphyrin
      III (UPIII), coproporphyrin I (CPI), coproporphyrin III (CPIII), and total
      porphyrins were measured using High Performance Liquid Chromatography (HPLC)
      system. RESULTS: Almost all of the urinary porphyrin concentrations from the
      patients with bladder cancer were higher than those from healthy adults.
      Moreover, 8h after ALA administration, urinary UPI and CPI showed high
      sensitivity (100 for UPI and CPI) and specificity (96.4 for UPI and 91.4 for
      CPI). CONCLUSION: These results indicate that the presence of urinary porphyrins
      after administration of ALA may function as tumor biomarkers. This method
      represents a possible new tumor screening method called photodynamic screening
      (PDS) using ALA-induced porphyrins.

PMID- 24284102
TI  - Cyanines in photodynamic reaction assisted by reversible electroporation--in
      vitro study on human breast carcinoma cells.
AB  - BACKGROUND: Ineffective drug delivery is a vast problem of anticancer therapies.
      The aim of this study was to investigate the possibility of enhancement of
      cyanines transport through the cell membrane by electroporation and to evaluate a
      photodynamic activity of these compounds. METHODS: We evaluated in vitro the
      effectiveness of photodynamic reaction with cyanines on breast adenocarcinoma
      cells (MCF-7/WT) and normal Chinese hamster ovary cells (CHO) lacking voltage
      dependent ion channels, alone and combined with electropermeabilization. Among
      six cyanines tested, two compounds could be indicated as good therapeutic
      candidates: IR-775 and IR-786. Cellular effects were assessed with MTT assay
      reporting cell mitochondrial activity and with SRB assay based on the measurement
      of cellular protein content. Cyanines localization was observed with confocal
      microscope. RESULTS: Photodynamic reaction of MCF-7/WT cells with IR-775 and IR
      786 did not result in cellular dysfunction. Electric field intensities and pulse
      duration, non-toxic for cells, significantly increased photocytotoxicity of the
      cyanines after electropermeabilization with IR-775 and IR-786. Much shorter
      exposure times were efficient for cyanines in photodynamic reaction assisted by
      electroporation (10 min instead of 24h). CONCLUSIONS: Our results indicate that
      electroporation of cancerous cells in the presence of cyanine dyes could increase
      the uptake of the photosensitizer, which correlates with a higher cytotoxicity in
      the breast adenocarcinoma cell line. Electroporation may be an attractive
      delivery system for photosensitizers in photodynamic therapy, enabling
      application of new compounds and reduction of drug dose and exposure time.

PMID- 24284103
TI  - Photodynamic therapy in treatment of cutaneous and choroidal melanoma.
AB  - Melanoma is a malignant, the most aggressive and dreaded skin cancer. This form
      of cancer arises from melanocytes and may grow rapidly and metastasize. Melanoma
      predominantly occurs in skin, but could also be found in the mouth, iris and
      retina of the eye. Melanoma is the most dangerous form of skin cancer, with a
      steeply rising incidence and a poor prognosis in its advanced stages. It is
      highly resistant to traditional chemotherapy and radiotherapy, although modern
      biological therapies are showing some promise. Photodynamic therapy (PDT), as a
      novel effective modality of the treatment of skin cancers, opens up new
      possibilities in melanoma treatment also. Many experimental photodynamic therapy
      studies were performed. The results of many experiments indicate that that
      photodynamic therapy may be a promising tool for adjuvant treatment in advanced
      melanoma. 

PMID- 24284104
TI  - Bis (3,5-diiodo-2,4,6-trihydroxyphenyl) squaraine photodynamic therapy induces in
      vivo tumor ablation by triggering cytochrome c dependent mitochondria mediated
      apoptosis.
AB  - BACKGROUND: Despite findings that photodynamic treatment with bis (3,5-diiodo
      2,4,6-trihydroxyphenyl) squaraine initiated tumor regression in mice skin,
      queries regarding its mode of action - answers to which will be functional to
      design clinical trials on squaraine based photodynamic therapy - remain
      unanswered. Our investigation reveals the in vivo mechanism of action of the
      photosensitizer. METHODS: Skin tumor was induced in Swiss albino mice using 7,12
      dimethyl benzanthacene. After the intraperitoneal administration of the dye in
      tumor induced mice, its concentration in subcellular fractions of the tumor
      tissue was determined fluorimetrically. Cytochrome c release from the
      mitochondrial membrane after the photodynamic treatment was analyzed. The
      observations stemming from this part lead to histopathological examination of
      tumor tissues. Apoptotic markers like caspase-3, Bcl-2 and Bax were also studied.
      RESULTS: Major portion of the dye accumulated in the mitochondria. Cytochrome c
      leakage from mitochondria after squaraine PDT suggests loss of mitochondrial
      membrane integrity, which was further confirmed by the results of
      histopathological analysis. The activity of caspase-3 was elevated, expression of
      Bcl-2 diminished and that of Bax increased - all these results show enhancement
      of apoptosis in the tumor region after the treatment. CONCLUSIONS: The results
      lead to the elucidation of mechanism of tumor destruction which proves to be
      mitochondria mediated apoptotic damage of tumor tissue. The study assumes
      significance since it defines the in vivo mode of action of a photosensitizer.
      Also, the query of how a squaraine based photosensitizer evokes tumor response is
      being dealt with here, for the first time.

PMID- 24284106
TI  - Increased number of fractionated irradiation sessions does not improve the
      cellular response to methyl aminolevulinate-mediated photodynamic therapy.
AB  - BACKGROUND: In the search to improve the efficacy of photodynamic therapy
      different approaches have been investigated until now. One of these approaches is
      the use of double fractionated irradiation schemes. This study aims to
      investigate the effect of increasing the numbers of fractionated irradiation
      sessions in methyl aminolevulinate-mediated photodynamic therapy on dysplastic
      oral keratinocytes by monitoring the changes in optical properties of cell
      culture. METHODS: Forty cell cultures were divided into four experimental groups
      (single, double and triple fractionated irradiation scheme and control). Cells
      were incubated with 1mM methyl aminolevulinate and after 2h they were exposed to
      laser radiation (lambda=635 nm, P=15 mW). The exposure time was 900 s for the
      single irradiation scheme, 300 s + 600 s for the double fractionated irradiation
      scheme with dark interval between sessions of 30 min and 300 s + 300 s + 300 s
      for the triple fractionated irradiation scheme with two dark intervals between
      sessions of 30 min. Two optical parameters (refractive index and extinction
      coefficient) were calculated from diffuse reflectance spectra of cell cultures
      using the Kramers-Kronig relations. RESULTS: The results demonstrate that the use
      of double fractionated irradiation scheme led to changes in optical parameters of
      cell cultures more important than the use of the single and triple fractionated
      irradiation schemes in photodynamic therapy. CONCLUSIONS: In conclusion,
      increasing too much the number of irradiation sessions cannot lead to an improved
      photodynamic effect.

PMID- 24284105
TI  - Immunocytochemical studies on the nuclear ubiquitous casein and cyclin-dependent
      kinases substrate following 5-aminolevulinicacid-mediated photodynamic therapy on
      MCF-7 cells.
AB  - BACKGROUND: Recent data indicates that nuclear ubiquitous casein and cyclin
      dependent kinases substrate (NUCKS) may play role in tumor growth. In present
      study authors examined whether photodynamic therapy with 5-aminolevulinic acid (5
      ALA) induces NUCKS expression in breast cancer cell line, MCF-7. METHODS: In the
      experiment concentration of 5-ALA was 6.5mM. Excitation wavelength was 630 +/- 20
      nm, total light dose of light 5 or 10 J/cm(2) and irradiance 60 mW/cm(2) was
      used. Cells were collected at established time points and Western blot and
      immunocytochemical studies were performed using antibody against NUCKS. RESULTS:
      Studies proved strong cytotoxic effects in cells following PDT with 6.5mM of
      precursor and 10 J/cm(2). Western blot analysis revealed the strongest expression
      of NUCKS at 7h after PDT. At next time points, 18 and 24h, expression of NUCKS
      decreased and became similar to that of control group. Further immunocytochemical
      studies showed very strong expression of NUCKS following PDT with 5-ALA and light
      irradiation of 5 J/cm(2). Early, at 0 h, that expression was predominantly seen
      in nuclei, while at 7h expression of NUCKS was observed in disseminated manner
      within entire cells in both nuclei and cytoplasm, with prevalence of cytoplasmic
      staining. CONCLUSIONS: Authors suggest that NUCKS is involved in cellular
      responses following PDT, and since parallel induction of NUCKS and proapoptotic
      marker Bax and inhibition of anti-apoptotic Bcl-2 was observed, this protein
      might also be involved in induction of apoptosis following PDT.

PMID- 24284107
TI  - Periungual Bowen's disease successfully treated with photodynamic therapy.
AB  - Bowen's disease or squamous cell carcinoma in situ is a malignancy of the skin
      confined to the epidermis that unusually involves the nail apparatus. The ideal
      treatment should complete clear the tumor, with preservation of the cosmetics and
      the function of the finger, which can be very difficult to achieve depending on
      tumor's location and the extension. The high cure rates for Bowen's disease and
      the principles of photodynamic therapy, suggest that this technique may be a
      great option in the management of this kind of lesion. Therefore, this is a case
      report of a 47-years-old man with diabetes and HIV+ serology who presented a
      patch of Bowen's disease at the distal phalange of the finger treated with
      photodynamic therapy in order to avoid surgical complications, a more aggressive
      treatment or even mutilation. An excellent response was reached, preserving all
      the structures of the nail, with clinical and histopathological cure and complete
      remission after two years of follow up. 

PMID- 24284108
TI  - Clearance mechanism of protoporphyrin IX from mouse skin after application of 5
      aminolevulinic acid.
AB  - BACKGROUND: 5-Aminolevulinic acid (ALA) or its esters mediated photodynamic
      therapy (PDT) is the most widely practiced form of PDT in dermatology. One of its
      advantages is that undesirable photosensitization lasts only for 24-48 h. In
      order to optimize ALA-PDT it is necessary to understand the mechanisms of
      intracellular production and clearance of PpIX (efflux from cells into blood
      stream and/or its conversion into haem). The aim of this study is to investigate
      the factors controlling the clearance of intracellular PpIX from healthy skin of
      mice. METHODS: PpIX was induced in mouse skin by topical or systemic application
      of ALA or by topical application of the iron chelator ethylenediaminetetraacetic
      acid (EDTA). Fluorescence spectroscopy was used to study PpIX kinetics in alive
      and dead skin. RESULTS: Topical application of ALA or EDTA leads to porphyrin
      production in living skin, but not in excised skin. The clearance rates of PpIX
      from alive and dead skin were the same in the absence of an intracellular ALA
      pool. The clearance half-life of EDTA-induced PpIX was 4-7 times longer than that
      of PpIX after application of ALA. CONCLUSIONS: Skin temperature and intracellular
      iron availability strongly affect PpIX clearance, while ALA application mode
      (topical versus systemic) and skin viability (dead versus alive) have no
      influence on PpIX decay. These results demonstrate that the clearance kinetics of
      PpIX from skin are determined mostly by the conversion of PpIX into haem, while
      the cellular efflux of PpIX into blood plays a minor role.

PMID- 24284109
TI  - Huge Bowen's disease: a pitfall of topical photodynamic therapy.
AB  - Bowen's disease (BD) is one of the major histological types of nonmelanoma skin
      cancer. With challengeable "multiple and large" patches of BD, topical
      photodynamic therapy (PDT) has been considered as a first-line effective modality
      for decades. However, there was no general consensus among authors about the
      definition of "large BD". Herein, we have experienced two cases of huge BD which
      has over 10 cm in diameter with resistance to topical PDT. Our cases suggest that
      topical PDT is likely to show a much less satisfactory effect for huge BD than we
      have expected, and the previously specified indication of topical PDT ("multiple,
      larger lesion") seems the fallacy of hasty generalization. Therefore, it is
      required that further cut-off value of size for suitable candidate for topical
      PDT would be clarified. 

PMID- 24284110
TI  - Efficacy of 5-Aminolevulinic Acid Photodynamic Therapy in treatment of nasal
      inverted papilloma.
AB  - OBJECTIVE: Evaluate the efficacy of 5-Aminolevulinic Acid Photodynamic Therapy
      (PDT) in medical treatment of nasal inverted papilloma (NIP). METHODS: Three
      patients with nasal inverted papilloma were treated with 5-Aminolevulinic Acid
      Photodynamic Therapy at our department from April to September 2012. The efficacy
      and adverse effects of 5-Aminolevulinic Acid Photodynamic Therapy were evaluated
      during 6-8 months of follow-up medical examination. RESULTS: After treated with 5
      Aminolevulinic Acid Photodynamic Therapy, the nasal inverted papillomas were
      removed. No recurrence was found during the 6-8 months of follow-up medical
      examination. The major adverse effects were mild erosion, pain, and exudation.
      CONCLUSION: 5-Aminolevulinic Acid Photodynamic Therapy appears to be an effective
      treatment of nasal inverted papilloma. It can clear the papilloma lesions and is
      well tolerated by the patients.

PMID- 24284111
TI  - Microendoscopy for hypericin fluorescence tumor diagnosis in a subcutaneous
      glioma mouse model.
AB  - BACKGROUND: New treatment strategies for malignant gliomas are indispensible, due
      to the poor prognosis for patients. Fluorescence diagnosis (FD) and photodynamic
      therapy (PDT) are currently under intensive investigation and seem to improve the
      prognosis. Especially for deep seated malignant brain lesions and in order to
      optimize therapy new diagnostic tools are needed. METHODS: In a syngeneic
      subcutaneous glioma mouse model we investigated the time dependent hypericin
      (HYP) uptake in malignant tumor tissue by microendoscopically fluorescence
      measurements. The HYP fluorescence in tumor was also detected by fluorescence
      microscopy (FM) and was compared to endoscopic data. RESULTS: Both methods,
      microendoscopy and FM, demonstrated time dependent HYP uptake in subcutaneously
      implanted mouse glioma. Maximum of HYP uptake was achieved after 6h, measured
      with both methods. FM reached a 10-fold increase in fluorescence intensity
      compared to the autofluorescence. Measured by microendoscopy a 2.2-fold HYP
      fluorescence intensity compared to the autofluorescence was detected.
      Microendoscopy enables visualization of small vessels even in healthy brain
      tissue by intravascular HYP fluorescence. CONCLUSION: The new developed
      microendoscope enables not only fluorescence based discrimination of tumor and
      healthy tissue, but also semiquantitative measurements of fluorescence
      intensities in vivo. Individual repetitive fluorescence diagnosis will become
      possible by this method and opens up new possibilities for determining optimal
      settings of light applications for PDT.

PMID- 24284112
TI  - Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high
      grade dysplasia in Barrett's oesophagus.
AB  - BACKGROUND: Barrett's high grade dysplasia (HGD) is a pre-malignant condition
      which requires treatment with either oesophagectomy or ablative endoscopic
      therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy
      (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded
      PDT due to improved efficacy and safety profile there remains a significant
      cohort of patients previously treated by PDT where the long term outcome is
      unclear. This study's aim was to assess the long term efficacy of PDT in patients
      with Barrett's HGD. METHODS: Between June 2002 and 2007 21 patients (16 male,
      median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received
      intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior
      to endoscopic light activation by laser light at 630 nm. The patients returned at
      6-12 weekly intervals for repeat endoscopy and biopsy. RESULTS: Sixteen patients
      remained free of HGD at median 62 (range 36-114) months. Three patients developed
      adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated
      endoscopically with RFA and YAG laser, while one patient had surgical resection.
      Four patients developed recurrent HGD treated with repeat PDT. There was a
      significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post
      PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients
      developed photosensitivity reactions. CONCLUSION: PDT successfully ablated HGD in
      84% of patients and could therefore still be considered an effective salvage
      treatment for this condition in patients with co-morbidities precluding them for
      surgical resection.

PMID- 24284113
TI  - Safe ablation of the anal mucosa and perianal skin in rats using Photodynamic
      Therapy--a promising approach for treating Anal Intraepithelial Neoplasia.
AB  - BACKGROUND: Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous
      carcinoma, is increasingly detected in individuals with impaired immune function.
      However, choices for effective, low morbidity treatment are limited. Photodynamic
      Therapy (PDT) is promising as it is known to ablate more proximal
      gastrointestinal mucosa with safe healing, without damage to underlying muscle.
      It can also ablate skin with safe healing and minimal scarring. METHODS:
      Pharmacokinetics: Normal rats were sensitised with 200mg/kg 5-aminolaevulinic
      acid (ALA) and killed 1-8h later. Anal tissues were examined by fluorescence
      microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active
      derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal
      rats were sensitised similarly 3h later, laser light (635 nm) was delivered. Anal
      canal: 50-150 J/cm using 1cm diffuser fibre; for peri-anal skin, 50-200 J/cm(2),
      using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28 days
      later and the anal region removed for histological examination. RESULTS:
      Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio
      mucosa: muscle, 6, seen at same time. PDT. Anal canal 50 J/cm: complete mucosal
      ablation by 3 days, complete regeneration by 28 days. Higher energies caused
      muscle damage with scarring. Peri-anal skin: 200 J/cm(2); complete ablation of
      skin, including appendages, complete healing by 28 days. Minimal effect with
      lower energy. CONCLUSION: ALA-PDT can ablate anal mucosa and peri-anal skin with
      safe healing and no underlying damage. However, over treatment can damage the
      sphincters. This technique is ready to undergo clinical trials.

PMID- 24284114
TI  - The effects of protoporphyrin IX-induced photodynamic therapy with and without
      iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic
      and hyperoxic conditions.
AB  - BACKGROUND: Photodynamic therapy requires the combined interaction of a
      photosensitiser, light and oxygen to ablate target tissue. In this study we
      examined the effect of iron chelation and oxygen environment manipulation on the
      accumulation of the clinically useful photosensitiser protoporphyrin IX (PpIX)
      within human squamous epithelial carcinoma cells and the subsequent ablation of
      these cells on irradiation. METHODS: Cells were incubated at concentrations of
      5%, 20% or 40% oxygen for 24h prior to and for 3h following the administration of
      the PpIX precursors aminolevulinic acid (ALA), methyl aminolevulinate (MAL) or
      hexylaminolevulinate (HAL) with or without the iron chelator 1,2-diethyl-3
      hydroxypyridin-4-one hydrochloride (CP94). PpIX accumulation was monitored using
      a fluorescence plate reader, cells were irradiated with 37 J/cm(2) red light and
      cell viability measured using the neutral red uptake assay. RESULTS: Manipulation
      of the oxygen environment and/or co-administration of CP94 with PpIX precursors
      resulted in significant changes in both PpIX accumulation and photobleaching.
      Incubation with 5% or 40% oxygen produced the greatest levels of PpIX and
      photobleaching in cells incubated with ALA/MAL. Incorporation of CP94 also
      resulted in significant decreases in cell viability following administration of
      ALA/MAL/HAL, with oxygen concentration predominantly having a significant effect
      in cells incubated with HAL. CONCLUSIONS: Experimentation with human squamous
      epithelial carcinoma cells has indicated that the iron chelator CP94
      significantly increased PpIX accumulation induced by each PpIX congener
      investigated (ALA/MAL/HAL) at all oxygen concentrations employed (5%/20%/40%)
      resulting in increased levels of photobleaching and reduced cell viability on
      irradiation. Further detailed investigation of the complex relationship of PDT
      cytotoxicity at various oxygen concentrations is required. It is therefore
      concluded that iron chelation with CP94 is a simple protocol modification with
      which it may be much easier to enhance clinical PDT efficacy than the complex and
      less well understood process of oxygen manipulation.

PMID- 24284115
TI  - Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of
      different severity of acne vulgaris.
AB  - OBJECTIVES: To investigate the efficacy and safety of low-concentration 5
      aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different
      severity of acne vulgaris and optimize the treatment regimen. METHODS: A self
      controlled multicenter clinical trial was carried out in 15 centers throughout
      China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT
      treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation.
      The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120
      J/cm(2). Clinical assessment was conducted before and after every treatment up to
      8 weeks. RESULTS: The effective rate overall and of grade II, III and IV are
      82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises
      significantly proportionally to the severity of acne (P<0.01). No significant
      differences are found in the efficacy between patients received 3-session and 4
      session PDT treatments (P>0.05). The count of inflammatory and non-inflammatory
      acne lesions gradually decrease after each treatment (P<0.01) and during the 8
      week follow up (P<0.01 or P<0.05). Maximum efficacy is obtained at 8 weeks after
      the treatment completion. CONCLUSIONS: A low-dose topical ALA-PDT regimen using
      5% ALA, 1h incubation and red light source of 3 treatment sessions is suggested
      as optimal scheme for the treatment of different severity of acne vulgaris in
      Chinese patients. Superior efficacy is found in severe cystic acne of grade IV
      with mild side effects.

PMID- 24284116
TI  - Optimizing the antitumor selectivity of PVP-Hypericin re A549 cancer cells and
      HLF normal cells through pulsed blue light.
AB  - Photodynamic therapy (PDT) is based on the preferential accumulation of
      photosensitizer in cancer cells with subsequent cytotoxicity mediated by singlet
      oxygen production after light excitation. As photosensitizers accumulate also in
      the surrounding non-cancer cells, the risk of damaging them by photosensitization
      is a limitation of PDT. Thus, minimizing the side-effects of PDT on normal cells
      is one of the challenging problems in medical practice. This paper studies the
      PDT side-effects of PVP-Hypericin (PVP: polyvinylpyrrolidone) photosensitizer
      excited with continuous or pulsed irradiation, on combined cell lines of human
      lung carcinoma epithelial cells (A549) and normal primary human lung fibroblast
      cells (HLF). In vitro PDTs are performed using pulsed or continuous irradiation
      with irradiance intensities I(*)=1.59, 6.34 and 14.27 mW/cm(2). The LED pulse
      lengths L are 0.127, 1.29, 13, 54.5 and 131 ms. Then fluorescence and
      phototoxicity of PVP-Hypericin in the A549 cancer cells are compared with those
      of HLF normal cells. Although, PVP-Hypericin accumulates more in A549 cancer
      cells, the results show that HLF cells produce dose-dependent photoreactions in
      the presence of photosensitizer. PVP-Hypericin induces the most optimized
      anticancer efficacy with moderate side-effects for I(*)=14.27 mW/cm(2) and L=131
      ms.

PMID- 24284117
TI  - Inactivation of Staphylococcus aureus by photodynamic action of hypocrellin B.
AB  - OBJECTIVE: Staphylococcus aureus is a common opportunistic pathogen causing human
      infections. In the present study, we investigated photodynamic inactivation on S.
      aureus using hypocrellin B from a traditional Chinese herb. MATERIALS AND
      METHODS: After incubation of S. aureus cells with different concentrations of
      hypocrellin B for 60 min, subsequent light irradiation from a novel LED light
      source with wavelength of 470 nm was combined with the energy density of 0.3
      J/cm(2). Phototoxicity of hypocrellin B on S. aureus was investigated by colony
      forming unit assay. Membrane permeability was measured using confocal laser
      scanning microscopy (CLSM) with propidium iodide (PI) staining. Intracellular
      reactive oxygen species (ROS) level was measured using flow cytometry (FCM) with
      DCFH-DA staining. Morphology and structure of treated and controlled bacteria
      were observed using transmission electron microscopy (TEM). RESULTS: Activity of
      S. aureus was substantially inhibited by photodynamic action in hypocrellin B
      dose-dependent manner. Notable damage to S. aureus were found in TEM after
      photodynamic treatment of hypocellin B. Red fluorescence of PI dye was observed
      more frequently in bacterial cells treated by photodynamic action of hypocrellin
      B than those of bacterial cells treated by the controls including sham control,
      hypocrellin B treatment alone and light irradiation alone. Intracellular ROS
      increase was also found in S. aureus treated by photodynamic action of
      hypocrellin B. CONCLUSION: Photodynamic action of hypocrellin B markedly
      increased intracellular ROS level and caused damage to membrane permeability,
      resulting in cell death of S. aureus.

PMID- 24284118
TI  - Access to a novel near-infrared photodynamic therapy through the combined use of
      5-aminolevulinic acid and lanthanide nanoparticles.
AB  - BACKGROUND: There have been considerable efforts to develop photodynamic therapy
      (PDT) for cancer, in which photoirradiation of a sensitizer delivered near cancer
      cells results in the conversion of oxygen into active species, causing cell
      destruction. Aiming at the best cancer selectivity, one PDT method employed
      protoporphyrin IX (PPIX), which selectively accumulated in cancer cells after
      oral administration of 5-aminolevulinic acid (ALA). The drawback, however, is
      that blue incident lights are required to excite PPIX, resulting in low tissue
      penetrability, and therefore limiting its application to surface cancers.
      METHODS: To overcome the low penetrability of the incident light, we employed a
      light energy upconverter, lanthanide nanoparticle (LNP), which, upon irradiation
      with highly penetrative near-infrared (NIR) radiation, emits visible light within
      the Q-band region of PPIX absorbance allowing its sensitization. To discover the
      optimum conditions for the LNP-assisted PDT, the cytotoxicity and PPIX
      sensitizability of LNPs were first studied. Then, the LNP-assisted PDT was
      validated using the MKN45 cell line: cells were pretreated with ALA and LNP,
      irradiated with a 975-nm diode laser, and subjected to MTT assay to measure cell
      viability. RESULTS: The singlet oxygen generation on NIR-irradiation of the PPIX
      LNP mixture was proved, indicating that the emission from LNP could excite the
      PPIX sensitizer. An intermittent NIR-irradiation for 32 min of MKN45, pretreated
      with LNP (1mg/mL) and ALA (2mM), caused 87% cell destruction. CONCLUSIONS: The
      potential applicability of the NIR-irradiation PDT with ALA- and LNP-pretreated
      cancer cells was demonstrated.

PMID- 24284119
TI  - Photodynamic inactivation of Staphylococcus aureus and methicillin-resistant
      Staphylococcus aureus with Ru(II)-based type I/type II photosensitizers.
AB  - BACKGROUND: The introduction of new disinfection and sterilization methods, such
      as antimicrobial photodynamic therapy, is urgently needed for the healthcare
      industry, in particular to address the pervasive problem of antibiotic
      resistance. This study evaluated the efficacy and the mechanisms of photodynamic
      antimicrobial chemotherapy (PACT), also known as photodynamic inactivation (PDI)
      of microorganisms, induced by novel Ru(II)-based photosensitizers against
      Staphylococcus aureus and methicillin-resistant S. aureus strains. METHODS: The
      photodynamic antibacterial effects of a new class of Ru(II)-based
      photosensitizers (TLD1411 and TLD1433) were evaluated against a strain of S.
      aureus (ATCC 25923) and a methicillin-resistant strain of S. aureus (MRSA, ATCC
      33592). Bacterial samples were dosed with a range of photosensitizer
      concentrations (0.3-12 MUM) and exposed to 530 nm light (90J cm(-2)) in normoxic
      conditions (ambient atmosphere) and in hypoxic conditions (0.5% O2). RESULTS:
      Both photosensitizers exerted photodynamic inactivation (PDI) of the
      microorganisms in normoxia, and this activity was observed in the nanomolar
      regime. TLD1411 and TLD1433 maintained this PDI potency under hypoxic conditions,
      with TLD1433 becoming even more active in the low-oxygen environment. CONCLUSION:
      The observation of activity in hypoxia suggests that there exists an oxygen
      independent, Type I photoprocess for this new class of compounds in addition to
      the typical Type II pathway mediated by singlet oxygen. The intrinsic positive
      charge of the Ru(II) metal combined with the oxygen independent activity
      demonstrated by this class of photosensitizers presents a new strategy for
      eradicating both gram-positive and gram-negative bacteria regardless of
      oxygenation level.

PMID- 24284120
TI  - Photoelimination of Streptococcus mutans with two methods of photodynamic and
      photothermal therapy.
AB  - BACKGROUND: Increasing resistance of oral pathogens to conventional antibacterial
      agents has resulted to find alternative therapies to overcome resistance
      development problems; hence this in vitro study was carried out to investigate
      the efficacy of photoelimination of Streptococcus mutans with two methods of
      photodynamic and photothermal therapy. METHODS: Standard Suspensions of S. mutans
      were treated in two groups of photodynamic therapy with Toluidine blue O and
      Rhadachlorin((r)) and photothermal therapy by EmunDo((r)) and their individual
      light sources, then Bacterial suspension from each treatment was subcultured on
      the surface of Mueller-Hinton agar plates and bacterial growth was assessed. The
      results were analyzed by analysis of variance and Tukey test (p<0.05). RESULTS:
      After treatments significant reduction of S. mutans viability in planktonic
      culture was observed in both groups of photodynamic and photothermal therapy with
      no priority. CONCLUSION: Photoelimination can be a novel modality in the
      eradication of S. mutans colonies in near future.

PMID- 24284121
TI  - Branch retinal artery occlusion associated with photodynamic therapy in a
      circumscribed choroidal haemangioma.
AB  - We report a case with retinal arteriole occlusion after a single photodynamic
      therapy (PDT). A 33-year-old man presented with decreased visual acuity of the
      right eye, 20/200, for four months. Diagnosed as circumscribed choroidal
      haemangioma (CCH), he was treated with the PDT. Specifically, 6 mg/m(2) of
      verteporfin was administered intravenously in 10 min. Laser treatment was
      performed 15 min after the infusion with an exposure of 75 J/cm(2) for 125 s. The
      patient was followed up a week later and then every month for 5 months.
      Complaining about central visual field defect two days post treatment, he was
      diagnosed with inferior macular artery occlusion with FA. After three months
      further treatment, the tumor regressed completely but local retinal atrophy was
      observed. The best corrected visual acuity (BCVA) was 20/30 with visual field
      defect. Following this, extensive blood tests were performed, revealing no
      abnormality. Our result indicates that under certain conditions infarction of
      retinal arterioles can develop following PDT.

PMID- 24284123
TI  - Successful treatment of recalcitrant folliculitis barbae and pseudofolliculitis
      barbae with photodynamic therapy.
AB  - Folliculitis and pseudofolliculitis barbae typically affects men with curly hair
      who shave too close. Treatment modalities vary in effectiveness and include
      improved hair removal methods, topical corticosteroids, topical and oral
      antibiotics, and retinoids as well as laser surgery. We report a novel treatment
      of recalcitrant pseudofolliculitis barbae and confirm effectiveness in
      recalcitrant folliculitis in a 58-year old man who responded completely following
      photodynamic therapy with methyl aminolevulinate. CONCLUSION: Photodynamic
      therapy should be considered in recalcitrant folliculitis and pseudofolliculitis
      barbae.

PMID- 24284122
TI  - Electroporation enhances antimicrobial photodynamic therapy mediated by the
      hydrophobic photosensitizer, hypericin.
AB  - The effective transport of photosensitizers (PS) across the membrane and the
      intracellular accumulation of PS are the most crucial elements in antimicrobial
      photodynamic therapy (aPDT). However, due to the morphological complexity of Gram
      negative bacteria the penetration of PS is limited, especially hydrophobic PS.
      Electroporation (EP) could increase the effectiveness of aPDT, by promoting the
      formation of transient pores that enhance the permeability of the bacterial
      membrane to PS. In this study we evaluated the combination of aPDT mediated by
      the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive
      Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were
      exposed to light (590 nm) in the presence of hypericin (4 MUM), following
      electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E.
      coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we
      suggest that EP can potentiate the aPDT effect.

PMID- 24284124
TI  - Porphyrin profile in four human cell lines after supplementation with 5
      aminolaevulinic acid and its methyl ester.
AB  - Multiple factors can affect the synthesis of the prodrugs aminolaevulinic acid
      and its methyl ester to protoporphyrin. These may ultimately influence the
      efficacy of ALA-induced porphyrin as a photosensitiser for photodynamic therapy
      or fluorescence diagnosis. This study demonstrates the variation in total amount
      of porphyrin produced and cellular porphyrins synthesised in four different human
      cell lines after supplementation with these prodrugs. A non-invasive optical
      biopsy system was able to detect spectral changes associated with the more
      carboxylated porphyrins accumulating in oesophageal (OE19) and bladder (HT1197)
      carcinoma cells, and to a lesser extent neuroblastoma (SH-SY5Y) cells after a 24h
      incubation with the prodrugs. If the porphyrin profile changes during disease
      progression, or between normal and cancerous cells clinically, then the
      demonstrated non-invasive spectral analysis may be exploitable in distinguishing
      between normal, dysplastic and tumour tissue. Finally, the OE19 cell line was
      insensitive to photo-inactivation under the experimental conditions used, despite
      accumulating more porphyrin than the other cells lines. 

PMID- 24284125
TI  - Repetitive methylene blue-mediated photoantimicrobial chemotherapy changes the
      susceptibility and expression of the outer membrane proteins of Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Since bacterial multidrug efflux pumps mediate intracellular
      photosensitizer methylene blue, a change in the expression alters the
      susceptibility to photoantimicrobial chemotherapy (PACT) of Pseudomonas
      aeruginosa, which may occur following repetitive sublethal challenges. MATERIALS
      AND METHODS: We performed 10 consecutive, methylene blue-mediated PACT on one
      antibiotic-sensitive strain and three antibiotic-resistant strains of P.
      aeruginosa. Following each therapy, the surviving bacteria were collected for
      subsequent PACT. The susceptibility was compared for the pre- and the post
      treated strains following repetitive PACT. To explore the existence of efflux
      pumps, one of the inhibitors, namely Phe-Arg beta-naphthylamide dihydrochloride
      (PAbetaN 25 MUg/ml), was added. Profiles of outer membrane proteins were obtained
      for the pre-treated and the post-treated strains. RESULTS: The susceptibility of
      PACT did not correlate with the antibiotic sensitivity. Following ten PACT, there
      was no significant change in susceptibility for three tested strains, except for
      one antibiotic-resistant strain, for which the 10th generation became less
      susceptible than the original one. With 2-D electrophoresis, a change in the
      expression of outer membrane proteins was observed. PAbetaN successfully
      increased the phototoxicity in all tested strains, especially the less PACT
      susceptible 10th generation of the antibiotic-resistant strain. CONCLUSIONS:
      Following repetitive challenges, PACT had a consistent antimicrobial effect on
      three strains; however, one antibiotic-resistant strain, which was the most
      vulnerable to PACT, became more resistant after consecutive challenges. In
      addition, the post-PACT strain had different expression of outer membrane
      proteins, providing further evidence view that repetitive PACT with methylene
      blue could change the expression of efflux pumps.

PMID- 24284126
TI  - Photodynamic therapy for intractable bronchial lung cancer.
AB  - OBJECTIVE: To investigate the effectiveness and side effects of photofrin
      photodynamic therapy (PDT) for intractable bronchial lung cancer. METHODS: Thirty
      patients were classified as stage II-IV intractable bronchial lung cancer with
      lumen obstruction after they failed previous treatment regimens such as surgery,
      radiotherapy and chemotherapy. PDT was performed with 630 nm laser light (Diomed)
      delivered through cylinder diffusing tip quartz fibers that was passed through
      the biopsy channel of a flexible endoscope 48 h after intravenous injection of
      the photosensitizer photofrin (2mg/kg body weight). 72 h after the first
      irradiation, the endoscopic procedure was repeated, necrotic tissues were
      mechanically removed and the deep original lesions and newly exposed cancer
      lesions were re-treated, and, if necessary, the areas were cleaned repeatedly.
      RESULTS: The total response rate CR+PR was 86.7%, and the mean percentage of
      obstruction due to tumors at different treated sites decreased from 90% to 16.7%
      at discharge after PDT. The KPS score was significantly improved after PDT.
      CONCLUSIONS: PDT of intractable bronchial lung cancer effectively reduces the
      amount of lumen obstruction, and improves the patient's quality of life. It may
      be an effective palliative treatment with minor side effects on patients with
      advanced bronchial lung cancer.

PMID- 24284127
TI  - Lethal photosensitization of Porphyromonas gingivalis by their endogenous
      porphyrins under anaerobic conditions: an in vitro study.
AB  - BACKGROUND: Lethal photosensitization has been previously demonstrated in
      Porphyromonas gingivalis, but oxygen is considered to be essential to this
      process. However, since P. gingivalis is a periodontal pathogen which grows in
      the low oxygen conditions found in the subgingival crevice, it was considered
      prudent to study its photosensitivity in anaerobic conditions. METHODS: A series
      of experiments were undertaken to attempt to induce lethal photosensitization in
      P. gingivalis (ATCC 33277) under strict anaerobic conditions using two different
      405 nm light sources. Samples of P. gingivalis were grown on a blood-containing,
      solid growth medium before being suspended in saline and then exposed to 405 nm
      light delivered by either a hand-held light source (ToothcareTM) (11.4 mW/cm(2))
      or a laser pointer (328.5 mW/cm(2)). With the exception of the adjustment of the
      P. gingivalis suspensions to a fixed optical density, the experiments were
      carried out in their entirety within an anaerobic chamber. RESULTS: The lowest
      Toothcare light dose tested (0.34 J/cm(2); 30s) yielded a statically significant
      kill of 63.4% which increased to 94.1% kill at higher light doses (3.42 J/cm(2);
      300 s). The laser pointer similarly achieved kills of 90.2% at the lower light
      dose tested (9.86 J/cm(2); 30s) and 94.5% kill at the highest light dose (98.55
      J/cm(2); 300 s). CONCLUSIONS: Lethal photosensitization can be instigated in
      planktonic suspensions of P. gingivalis at 405 nm delivered by hand-held devices
      under anaerobic conditions. This suggests the possibility that lethal
      photosensitization occurred by the oxygen-independent type I pathway as oppose to
      the oxygen-dependent type II pathway.

PMID- 24284128
TI  - Correlations between photoactivable porphyrins' fluorescence, erythema and the
      pain induced by PDT on normal skin using ALA-derivatives.
AB  - BACKGROUND: Photodynamic therapy (PDT) with precursors of photoactivable
      porphyrins is a well-established treatment modality for skin pathologies as well
      as hair removal. Pain is a major side effect thereof, and it affects the
      treatment compliance and acceptance. METHODS: Five male subjects underwent a PDT
      procedure on normal skin, either with a diode laser (635 nm) or a lamp (405 nm),
      3 or 6h after application of various precursors of photoactivable porphyrins (ALA
      1M; Metvix((r)) 1M; ALA-DGME 1M; ALA-DGME 3.66 M). Light doses ranged from 30 to
      150 J/cm(2) and irradiances were 100 or 180 mW/cm(2). Fluorescence measurements
      were performed just before PDT, pain was quantified during PDT, and erythema was
      determined 24h afterwards. RESULTS: Because precursor ALA-DGME was very selective
      for the pilosebaceous apparatus vs. the epidermis, we solely carried out the PDTs
      using this precursor. In the absence of light, no pain was reported. An increase
      in pain was observed when increasing the irradiance. A correlation was observed
      between the follicular fluorescence and the maximal pain score during PDT. A
      correlation was observed between follicular fluorescence and skin erythema, and
      between pain score and skin erythema. CONCLUSIONS: With our well-controlled PDT
      parameters and homogenous subjects' conditions, we showed that pain could be
      reduced by reducing irradiance during PDT procedures. With the various
      correlations observed, we conclude that both pain and PaP fluorescence are useful
      tools to predict the post-PDT tissue effects (side effects and outcome). We
      suggest that A? nerve fibres would be the best candidate as first generators of
      PDT-induced pain.

PMID- 24284129
TI  - Inactivation of multidrug resistant (MDR)- and extensively drug resistant (XDR)
      Mycobacterium tuberculosis by photodynamic therapy.
AB  - We investigated the effects of photodynamic therapy (PDT) on anti-tuberculosis
      (TB) activity by measuring inactivation rates, expressed as D-value, of MDR- and
      XDR-Mycobacterium tuberculosis (M. tb) clinical strains in vitro. Approximately
      10(6) colony forming unit per milliliter (CFU/ml) of the bacilli were irradiated
      with various doses of laser light after exposure to photosensitizers. Survival of
      M. tb was measured by enumerating CFU in 7H10 medium to measure D-values. No
      inactivation of M. tb was observed when exposed to photosensitizers (radachlorin
      or DH-I-180-3) only or laser light only (P>0.1). Treatment with a combination of
      photosentizer and laser inactivated M. tb although there was a significant
      difference between the types of photosensitizers applied (P<0.05). Linear
      inactivation curves for the clinical M. tb strains were obtained up to laser
      doses of 30 J/cm(2) but prolonged irradiation did not linearly inactivate M. tb,
      yielding sigmoid PDT inactivation curves. D-values of M. tb determined from the
      slope of linear regression lines in PDT were not significantly different and
      ranged from 10.50 to 12.13 J/cm(2) with 670 nm laser irradiation at 100 mW/cm(2)
      of the fluency rate, except for a drug-susceptible strain among the clinical
      strains tested. This suggests that PDT inactivated M. tb clinical strains
      regardless of drug resistance levels of the bacilli. Intermittent and repeated
      PDT allowed acceleration of the inactivation of the bacilli as a way to avoid the
      sigmoid inactivation curves. In conclusion, PDT could be alternative as a new
      option for treatment for MDR- and XDR-tuberculosis.

PMID- 24284131
TI  - Widespread psammoma body formation arising in the background of a uterine serous
      carcinoma.
AB  - This report highlights a very rare phenomenon of widespread psammomatous
      calcification without accompanying epithelium, present in the background of a
      uterine serous carcinoma. Psammomatous calcification is associated with benign
      and malignant pathology in different organ systems including the gynaecological
      tract. 

PMID- 24284130
TI  - The effect of light fractionation with a 2-h dark interval on the efficacy of
      topical hexyl-aminolevulinate photodynamic therapy in normal mouse skin.
AB  - BACKGROUND: Light fractionation with a 2-h dark interval increases the efficacy
      of topical aminolevulinic acid (ALA) photodynamic therapy (PDT). Hexyl
      aminolevulinate (HAL) is the hexyl ester of ALA. Both HAL and ALA lead to
      protoporphyrin IX (PpIX) accumulation in endothelial cells and to vascular
      effects, which are important for light fractionation. We investigated light
      fractionation for HAL-PDT in a mouse skin model and compared this with ALA.
      METHODS: Three illumination schemes were studied: (a) 100 J cm(-2) in a single
      illumination; (b) 50+50 J cm(-2) in a twofold illumination; (c) a small first
      light fraction until 50% of PpIX was photobleached (ca. 3 J cm(-2)), followed by
      97 J cm(-2) 2h later. PpIX fluorescence was measured continuously during
      illumination. Efficacy was evaluated by daily visual skin damage scoring up to 7
      days after PDT. RESULTS: Light fractionation showed a trend towards increased
      efficacy for HAL-PDT. Both the initial PpIX synthesis and the PpIX resynthesis
      during the dark interval were higher for ALA, but these were not correlated with
      efficacy. Single HAL-PDT was more effective than single ALA-PDT. Photobleaching
      rates of HAL and ALA were similar indicating similar biodistributions at depth.
      CONCLUSION: Our results provide evidence to support that light fractionation may
      be beneficial for HAL-PDT. We are cautious because we found only a non
      significant increase in response. However, combining our results with literature
      data suggest that the illumination scheme may be further optimized for HAL-PDT to
      potentially enhance the effect of light fractionation.

PMID- 24284132
TI  - Moderately differentiated peripheral adenocarcinoma of the lung with cilia.
AB  - We report an extremely rare case in which cilia were identifiable on light
      microscopic examination in cells of a moderately differentiated peripheral
      adenocarcinoma in the lung. The cells were positive for cytokeratin 7, and the
      cilia were highlighted by epithelial membrane antigen staining. The prognostic
      significance of these extremely well-differentiated ciliated tumor cells will be
      known only with long-term follow-up of the patient and analysis of more such
      tumors. 

PMID- 24284133
TI  - Histopathology of Keratoacanthoma Revisited: Utility of Orificial Size as a
      Diagnostic Adjunct.
AB  - BACKGROUND/AIMS: Given the defining histopathologic architecture of
      keratoacanthoma (KA), the aim of this study was to measure the crateriform
      orifice ("orificial size") in histopathologically crateriform lesions to
      ascertain its utility as an objective diagnostic histopathologic adjunct.
      METHODS: This cross-sectional, retrospective study included 97 cases with a
      histopathologic diagnosis of KA. We measured the "orificial size" using the
      ocular micrometer in a BH-2 Olympus microscope at 4* magnification, in a blinded
      manner with respect to information. Frequency of histopathologic features
      observed was also recorded. RESULTS: The average orificial size for different
      groups was as follows: 2.3 +/- 0.2 mm for cases with a clinical presentation of
      KA/keratotic papule (KP) (n = 30) versus 2.9 +/- 0.3 mm for other (n = 67), P =
      .18. Histopathologic findings in the 2 groups were as follows: crateriform
      architecture/epithelial lip and sharp demarcation of tumor from stroma (100% in
      both groups), fibrosis (29/30 vs 64/67), apoptotic keratinocytes (27/30 vs
      56/67), dermal islands of "glassy" keratinocytes (26/30 vs 54/67), entrapped
      elastic fibers (26/30 vs 49/67), and neutrophilic abscesses (11/30 vs 21/670 [P =
      not significant for all]. CONCLUSION: Our findings indicate that, in the
      appropriate clinical setting, a smaller orificial size, although predictive of a
      KA, in itself is not sufficient for a definitive diagnosis. Given that a major
      limitation is that this is a function of age of the lesion as orificial size
      depends on the evolution stage of the neoplasm with the largest diameter often
      evident in lesions at early stages of regression, for now correlation with
      histopathologic features such as presence of an epithelial lip, sharp demarcation
      of tumor from stroma, and fibrosis (present in >95% of cases of KAs) is required.

PMID- 24284134
TI  - Aggregated N-of-1 randomized controlled trials: modern data analytics applied to
      a clinically valid method of intervention effectiveness.
AB  - OBJECTIVE: Aggregated N-of-1 randomized controlled trials (RCTs) combined with
      multilevel modeling represent a methodological advancement that may help bridge
      science and practice in pediatric psychology. The purpose of this article is to
      offer a primer for pediatric psychologists interested in conducting aggregated N
      of-1 RCTs. METHODS: An overview of N-of-1 RCT methodology is provided and 2
      simulated data sets are analyzed to demonstrate the clinical and research
      potential of the methodology. RESULTS: The simulated data example demonstrates
      the utility of aggregated N-of-1 RCTs for understanding the clinical impact of an
      intervention for a given individual and the modeling of covariates to explain why
      an intervention worked for one patient and not another. CONCLUSIONS: Aggregated N
      of-1 RCTs hold potential for improving the science and practice of pediatric
      psychology.

PMID- 24284135
TI  - Acceptance of and attitudes towards Alzheimer's disease screening in elderly
      German adults.
AB  - BACKGROUND: Considering the discussion on implementing routine dementia screening
      in Germany, the objective of the current study was to validate the German version
      of the Perceptions Regarding Investigational Screening for Memory in Primary Care
      (PRISM-PC) questionnaire and to determine the acceptance of Alzheimer's disease
      screening in elderly German adults. METHODS: The German version of the PRISM-PC
      was administered to a subsample of participants who attended the Berlin Aging
      Study II (n = 506). The questionnaire was validated by exploratory as well as
      confirmatory factor analysis. RESULTS: Regarding acceptance of Alzheimer's
      disease screening (Section B) a single factor structure fitted best. In terms of
      attitudes regarding Alzheimer's disease (Section D), a hierarchical factor
      structure was modeled with the higher-order factor "Harms" covering the domains
      "Family Burden," "Dependence," "Emotional Suffering," "Stigma," and "Medical
      Care" on the one hand and the domain "Future Planning" on the other hand.
      Internal consistency of the different scales reached from alpha = 0.67 to alpha =
      0.94. Overall, 71.2% of the participants indicated that they wanted to be
      screened for Alzheimer's disease on a regular basis. CONCLUSIONS: This study
      suggests that acceptance can reliably be assessed with the section "Acceptance of
      Alzheimer's disease screenings" of the German PRISM-PC questionnaire.
      Furthermore, the majority of elderly German adults would like to be screened for
      Alzheimer's disease regularly, which might be an effective starting point in
      order to implement routine dementia screenings. As the sample is a convenience
      sample of (relatively) healthy older adults, generalizability of these results is
      limited.

PMID- 24284137
TI  - Sperm-egg interaction and functional assessment of springbok, impala and blesbok
      cauda epididymal spermatozoa using a domestic cattle in vitro fertilization
      system.
AB  - The study assesses the possibility to estimate the potential fertility of post
      thawed antelope (Antidorcas marsupialis), impala (Aepyceros melampus) and blesbok
      (Damaliscus dorcus phillipsi) epididymal sperm using homologous and heterologous
      IVF and the functioning of cattle IVF system to produce antelope embryos. Cauda
      epididymal sperm were collected from the antelope and cryopreserved under field
      conditions. In vitro matured domestic cow, blesbok and springbok oocytes were co
      incubated in modified-Tyrode Lactate (m-TL) IVF media with springbok, impala and
      blesbok sperm for heterologous IVF and springbok and blesbok sperm for homologous
      IVF. A group of presumptive zygotes from each treatment were examined for sperm
      penetration and male pronuclear formation after 18h and the remainder were
      cultured and evaluated for embryo cleavage 22h later. The study shows that
      Modified Tyrode Lactate in vitro fertilization media supports survivability,
      capacitation and hyperactivation of springbok, impala and blesbok sperm.
      Springbok, impala and blesbok post-thawed epididymal spermatozoa are capable of
      fertilizing domestic cow oocytes under conditions that support domestic cattle
      IVF. Penetration, male pronuclear formation and embryo cleavage did not differ
      (p>0.05) between cow oocytes inseminated with sperm from springbok, impala or
      blesbok however these parameters were higher (p<0.05) for oocytes inseminated
      with bull sperm. Modified Tyrode Lactate IVF media supported homologous
      fertilization and embryo development in springbok and blesbok however did not
      support blastocyst development. These findings suggest that cattle provide a
      useful model for evaluating springbok, impala and blesbok post-thawed cauda
      epididymal sperm functionality. Domestic cattle embryo culture conditions need to
      be modified to promote blastosyst development in these antelope species. Such
      research provides an important tool in assisted reproductive technology
      development when high biological value material is utilized for wild species
      recovery plans. 

PMID- 24284138
TI  - The Association Between ADHD and Antisocial Personality Disorder (ASPD): A
      Review.
AB  - OBJECTIVE: Children with ADHD have an increased risk of later developing
      personality disorders and criminal behavior. The object of the present review is
      to analyze the associations between ADHD and antisocial personality disorder
      (ASPD). METHOD: A review of literature was done using EMBASE, PsycINFO, and
      Medline databases. RESULTS: Eighteen prospective studies (n = 5,501) showed that
      ADHD with and without comorbid conduct disorder (CD) is a strong predictor for
      the risk of later development of antisocial personality disorder (ASPD). Some of
      the 13 cross-sectional/retrospective studies (n = 2,451) suggested that ADHD and
      CD might be a separate subtype of ADHD, that especially impulsivity in ADHD is a
      predictor for later development of ASPD, or that callous-unemotional traits in
      the ADHD children are called for a risk factor for later ASPD. CONCLUSION: There
      is an increased risk for children with ADHD with or without comorbid CD to
      develop later onset of antisocial personality disorder.

PMID- 24284140
TI  - Consensus ad idem: a protocol for development of consensus statements.

PMID- 24284139
TI  - Utility of neuropsychiatric tools in the differential diagnosis of dementia with
      Lewy bodies and Alzheimer's disease: quantitative and qualitative findings.
AB  - BACKGROUND: Discerning dementia with Lewy bodies (DLB) from Alzheimer's disease
      (AD) is one of the most common and challenging differential diagnoses at the
      memory clinic. Although the neuropsychiatric manifestations have been widely
      reported as one of the main key points in the differential diagnosis between
      these two diseases, to date no neuropsychiatric questionnaire has been
      specifically devised for this purpose. METHODS: We administered the
      Neuropsychiatric Inventory (NPI) and the Columbia University Scale for
      Psychopathology in Alzheimer's Disease (CUSPAD) to a memory clinic sample of 80
      patients with probable DLB and 85 age- and severity-matched patients with
      probable AD. Diagnosis of probable DLB was supported with a positive dopamine
      transporter SPECT scan. We examined the usefulness of these two neuropsychiatric
      tools designed for AD in the differential diagnosis between DLB and AD. We also
      investigated the correlations between psychotic symptoms and measures of
      cognitive and functional decline. RESULTS: Auditory hallucinations were very
      specific of DLB and were usually preceded by visual hallucinations.
      Misinterpretation of real visual stimuli (illusions) was more frequent in DLB.
      Delusions were both quantitatively and qualitatively different between DLB and
      AD: delusional misidentifications were significantly more characteristic of DLB,
      while paranoid delusions did not show specificity for DLB. CONCLUSIONS:
      Neuropsychiatric tools are useful to discriminate DLB from AD. Hallucinations and
      delusions are not only more frequent in DLB than in AD but also have distinct
      qualitative characteristics and patterns of progression that can help clinicians
      to make a more accurate differential diagnosis.

PMID- 24284142
TI  - CAGS Clinical Practice Committee report: the science of Clostridium difficile and
      surgery.

PMID- 24284143
TI  - The reliability of differentiating neurogenic claudication from vascular
      claudication based on symptomatic presentation.
AB  - BACKGROUND: Intermittent claudication can be neurogenic or vascular. Physicians
      use a profile based on symptom attributes to differentiate the 2 types of
      claudication, and this guides their investigations for diagnosis of the
      underlying pathology. We evaluated the validity of these symptom attributes in
      differentiating neurogenic from vascular claudication. METHODS: Patients with a
      diagnosis of lumbar spinal stenosis (LSS) or peripheral vascular disease (PVD)
      who reported claudication answered 14 questions characterizing their symptoms. We
      determined the sensitivity, specificity and positive and negative likelihood
      ratios (PLR and NLR) for neurogenic and vascular claudication for each symptom
      attribute. RESULTS: We studied 53 patients. The most sensitive symptom attribute
      to rule out LSS was the absence of "triggering of pain with standing alone"
      (sensitivity 0.97, NLR 0.050). Pain alleviators and symptom location data showed
      a weak clinical significance for LSS and PVD. Constellation of symptoms yielded
      the strongest associations: patients with a positive shopping cart sign whose
      symptoms were located above the knees, triggered with standing alone and relieved
      with sitting had a strong likelihood of neurogenic claudication (PLR 13).
      Patients with symptoms in the calf that were relieved with standing alone had a
      strong likelihood of vascular claudication (PLR 20.0). CONCLUSION: The classic
      symptom attributes used to differentiate neurogenic from vascular claudication
      are at best weakly valid independently. However, certain constellation of
      symptoms are much more indicative of etiology. These results can guide general
      practitioners in their evaluation of and investigation for claudication.

PMID- 24284144
TI  - Functional outcomes and cost estimation for extra-articular and simple intra
      articular distal radius fractures treated with open reduction and internal
      fixation versus closed reduction and percutaneous Kirschner wire fixation.
AB  - BACKGROUND: We sought to compare direct costs and clinical and radiographic
      outcomes for distal radius fractures (DRF) treated with open reduction internal
      fixation with volar locking plates (VLP) versus closed reduction and percutaneous
      pinning (CRPP). METHODS: We identified patients with AO-type A and C1 DRFs from a
      prospective database. Outcomes were assessed at 6 weeks and at 3, 6 and 12
      months, and surgical care costs were estimated. RESULTS: Twenty patients were
      treated with CRPP and 24 with VLP. There were no significant differences in
      patient-rated wrist evaluation (PRWE) scores between the 2 groups at any time
      point (mean 16.2 +/- 23.1 in the CRPP group v. 21.5 +/- 23.6 in the VLP group, p
      = 0.91). Overall alignment was maintained in both groups; however, there was a
      greater loss of radial height over time with CRPP than VLP (0.97 mm v. 0.25 mm, p
      = 0.018). The mean duration of surgery was longer for VLP than CRPP (113.9 +/-
      39.5 min v. 86.5 +/- 7.8 min, p = 0.029), but there were fewer clinic visits (5.2
      +/- 1.4 v. 7.8 +/- 1.3, p < 0.001) and fewer radiographs (7.4 +/- 2.7 v. 9 +/-
      2.4, p = 0.031). The total cost per case was greater for VLP than CRPP ($1637.27
      v. $733.91). CONCLUSION: Based on PRWE scores, VLPs did not offer any significant
      advantage over CRPP in patients with simple fracture types between 3 and 12
      months, but they were much more costly. Whether VLP offers any functional
      advantage earlier in recovery, thereby justifying their expense, requires further
      investigation in the form of a prospective randomized trial with a detailed cost
      analysis.

PMID- 24284145
TI  - Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care
      centre.
AB  - BACKGROUND: We sought to evaluate the adequacy of follow-up of thyroid cancer
      patients at a Canadian centre. METHODS: We mailed a survey to the family
      physicians of thyroid cancer patients and analyzed the findings relative to
      follow-up guidelines published by the American Thyroid Association (ATA).
      Statistical significance between early and late follow-up patterns was analyzed
      using the chi(2) test. RESULTS: Our survey response rate was 56.2% (91 of 162).
      The time from operation ranged from 1.24-7.13 (mean 3.96) years, and 87.9% of
      patients had undergone a physical exam within the previous year. Only 37.4% and
      14% of patients had a serum thyroglobulin measurement within 6 and between 6 and
      12 months before the survey, respectively. Thyroid simulating hormone (TSH)
      levels were measured within the prior 6 months in 67% of patients and between 6
      and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 MUIU/L) in 24.2% of
      patients, 0.1-2 MUIU/L in 44% and greater than 2 MUIU/L in 17.6%. Ultrasonography
      was the most common imaging test performed. CONCLUSION: There is significant
      variation in the follow-up patterns of patients with thyroid cancer, and there is
      considerable deviation from current ATA guidelines.

PMID- 24284146
TI  - Quality of inguinal hernia operative reports: room for improvement.
AB  - BACKGROUND: Operative reports (ORs) serve as the official documentation of
      surgical procedures. They are essential for optimal patient care, physician
      accountability and billing, and direction for clinical research and auditing.
      Nonstandardized narrative reports are often of poor quality and lacking in
      detail. We sought to audit the completeness of narrative inguinal hernia ORs.
      METHODS: A standardized checklist for inguinal hernia repair (IHR) comprising 33
      variables was developed by consensus of 4 surgeons. Five high-volume IHR surgeons
      categorized items as essential, preferable or nonessential. We audited ORs for
      open IHR at 6 academic hospitals. RESULTS: We audited 213 ORs, and we excluded 7
      femoral hernia ORs. Tension-free repairs were the most common (82.5%), and the
      plug-and-patch technique was the most frequent (52.9%). Residents dictated 59% of
      ORs. Of 33 variables, 15 were considered essential and, on average, 10.8 +/- 1.3
      were included. Poorly reported elements included first occurrence versus
      recurrent repair (8.3%), small bowel viability in incarcerated hernias (10.7%)
      and occurrence of intraoperative complications (32.5%). Of 18 nonessential
      elements, deep vein thrombosis prophylaxis, preoperative antibiotics and urgency
      were reported in 1.9%, 11.7% and 24.3% of ORs, respectively. Repair-specific
      details were reported in 0 to 97.1% of ORs, including patch sutured to tubercle
      (55.1%) and location of plug (67.0%). CONCLUSION: Completeness of IHR ORs varied
      with regards to essential and nonessential items but were generally incomplete,
      suggesting there is opportunity for improvement, including implementation of a
      standardized synoptic OR.

PMID- 24284147
TI  - On-pump beating-heart versus conventional coronary artery bypass grafting for
      revascularization in patients with severe left ventricular dysfunction: early
      outcomes.
AB  - BACKGROUND: We sought to evaluate the effects of on-pump beating-heart versus
      conventional coronary artery bypass grafting techniques requiring cardioplegic
      arrest in patients with coronary artery disease with left ventricular
      dysfunction. METHODS: We report the early outcomes associated with survival,
      morbidity and improvement of left ventricular function in patients with low
      ejection fraction who underwent coronary artery bypass grafting between August
      2009 and June 2012. Patients were separated into 2 groups: group I underwent
      conventional coronary artery bypass grafting and group II underwent an on-pump
      beating-heart technique without cardioplegic arrest. RESULTS: In all, 131
      patients underwent coronary artery bypass grafting: 66 in group I and 65 in group
      II. Left ventricular ejection fraction was 26.6% +/- 3.5% in group I and 27.7% +/
      4.7% in group II. Left ventricular end diastolic diameter was 65.6 +/- 3.6 mm in
      group I and 64.1 +/- 3.2 mm in group II. There was a significant reduction in
      mortality in the conventional and on-pump beating-heart groups (p < 0.001).
      Perioperative myocardial infarction and low cardiac output syndrome were higher
      in group I than group II (both p < 0.05). Improvement of left ventricular
      function after the surgical procedure was better in group II than group I.
      CONCLUSION: The on-pump beating-heart technique is the preferred method for
      myocardial revascularization in patients with left ventricular dysfunction. This
      technique may be an acceptable alternative to the conventional technique owing to
      lower postoperative mortality and morbidity.

PMID- 24284148
TI  - Validity of vascular trauma codes at major trauma centres.
AB  - BACKGROUND: The use of administrative databases in vascular injury research has
      been increasing, but the validity of the diagnosis codes used in this research is
      uncertain. We assessed the positive predictive value (PPV) of International
      Classification of Diseases, tenth revision (ICD-10), vascular injury codes in
      administrative claims data in Ontario. METHODS: We conducted a retrospective
      validation study using the Canadian Institute for Health Information Discharge
      Abstract Database, an administrative database that records all hospital
      admissions in Canada. We evaluated 380 randomly selected hospital discharge
      abstracts from the 2 main trauma centres in Toronto, Ont., St.Michael's Hospital
      and Sunnybrook Health Sciences Centre, between Apr. 1, 2002, and Mar. 31, 2010.
      We then compared these records with the corresponding patients' hospital charts
      to assess the level of agreement for procedure coding. We calculated the PPV and
      sensitivity to estimate the validity of vascular injury diagnosis coding.
      RESULTS: The overall PPV for vascular injury coding was estimated to be 95% (95%
      confidence interval [CI] 92.3-96.8). The PPV among code groups for neck, thorax,
      abdomen, upper extremity and lower extremity injuries ranged from 90.8 (95% CI
      82.2-95.5) to 97.4 (95% CI 91.0-99.3), whereas sensitivity ranged from 90% (95%
      CI 81.5-94.8) to 98.7% (95% CI 92.9-99.8). CONCLUSION: Administrative claims
      hospital discharge data based on ICD-10 diagnosis codes have a high level of
      validity when identifying cases of vascular injury. LEVEL OF EVIDENCE:
      Observational Study Level III.

PMID- 24284149
TI  - Jejunostomy tube feeding in patients undergoing esophagectomy.
AB  - BACKGROUND: Surgical jejunostomy tubes are a routine part of elective
      esophagectomies in patients with carcinomas and provide a route for nutritional
      support in those who experience complications. We wished to determine how
      frequently oral intake is delayed and the amount of nutrition delivered via the
      jejunostomy tube. METHODS: We reviewed the charts of all adults undergoing
      esophagectomy for carcinoma between January 2000 and June 2008. We determined the
      proportion of patients unable to resume oral nutrition after 8 days and the
      amount of nutrition delivered in each of the 8 days. RESULTS: In all, 111
      patients underwent elective esophagectomy for carcinoma, and 103 had a
      jejunostomy tube placed. The mean age was 67 +/- 10.8 years. The median time to
      oral intake was 7 (interquartile range 7-11) days. Seventy-four (67%) patients
      resumed oral intake within 8 days. The mean nutrition delivered by jejunostomy
      within the first 8 days as a percentage of the target was 45.6% (95% confidence
      interval 41.2%-49.9%). Six (5.4%) patients experienced complications attributable
      solely to the jejunostomy tube; 3 (2.9%) required surgery. Forty (38.8%) patients
      had abdominal issues serious enough to warrant delaying the progression of
      feeding. CONCLUSION: Two-thirds of patients undergoing elective esophagectomy
      were tolerating oral intake by the end of the eighth postoperative day, and less
      than half of the target nutrition was delivered over the first 8 days. We now
      selectively place surgical jejunostomy tubes in patients undergoing elective
      esophagectomies.

PMID- 24284150
TI  - Uptake of an innovation in surgery: observations from the cluster-randomized
      Quality Initiative in Rectal Cancer trial.
AB  - BACKGROUND: Theory suggests the uptake of a medical innovation is influenced by
      how potential adopters perceive innovation characteristics and by characteristics
      of potential adopters. Innovation adoption is slow among the first 20% of
      individuals in a target group and then accelerates. The Quality Initiative in
      Rectal Cancer (QIRC) trial assessed if rectal cancer surgery outcomes could be
      improved through surgeon participation in the QIRC strategy. We tested if
      traditional uptake of innovation concepts applied to surgeons in the experimental
      arm of the trial. METHODS: The QIRC strategy included workshops, access to
      opinion leaders, intraoperative demonstrations, postoperative questionnaires, and
      audit and feedback. For intraoperative demonstrations, a participating surgeon
      invited an outside surgeon to demonstrate optimal rectal surgery techniques. We
      used surgeon timing in a demonstration to differentiate early and late adopters
      of the QIRC strategy. Surgeons completed surveys on perceptions of the strategy
      and personal characteristics. RESULTS: Nineteen of 56 surgeons (34%) requested an
      operative demonstration on their first case of rectal surgery. Early and late
      adopters had similar perceptions of the QIRC strategy and similar
      characteristics. Late adopters were less likely than early adopters to perceive
      an advantage for the surgical techniques promoted by the trial (p = 0.023).
      CONCLUSION: Most traditional diffusion of innovation concepts did not apply to
      surgeons in the QIRC trial, with the exception of the importance of perceptions
      of comparative advantage.

PMID- 24284151
TI  - Complications following hip arthroscopy: a retrospective review of the McMaster
      experience (2009-2012).
AB  - BACKGROUND: The use of hip arthroscopy has been steadily rising as technology,
      experience and surgical education continue to advance. Previous reports of the
      complication rate associated with hip arthroscopy have varied. The purpose of
      this study was to report our experience with hip arthroscopy complications at a
      single Canadian institution (McMaster University). METHODS: We performed a
      retrospective chart review of 2 hip arthroscopists at the same institution to
      identify patients who had undergone the index surgery and had been followed for a
      minimum of 6 months postoperatively. We used a standard data entry form to
      collect information on patient demographic and clinical characteristics,
      including age, sex, surgical indication and type of complication if any. RESULTS:
      A total of 211 patients underwent 236 hip arthroscopies. The mean age at time of
      surgery was 37 +/- 13 years and mean follow-up was 394 +/- 216.5 days. The
      overall complication rate associated with hip arthroscopy was 4.2% (95%
      confidence interval 2.3%-7.6%). We identified 4 major and 6 minor complications.
      CONCLUSION: Overall, hip arthroscopy appears to be safe, with minor complications
      occurring more frequently than major ones. However, surgeons should recognize the
      possibility of serious complications associated with this procedure. Future
      research should focus on prospective designs looking for potential prognostic
      factors associated with hip arthroscopy complications.

PMID- 24284152
TI  - CAGS and ACS evidence based reviews in surgery. 47. Does the long-term use of
      aspirin decrease the risk of death due to cancer?

PMID- 24284153
TI  - Self-directed practice schedule enhances learning of suturing skills.
AB  - BACKGROUND: Most preoperative surgical training programs experience challenges
      with the availability of expert surgeons to teach trainees. Some research
      suggests that trainees may benefit from being allowed to actively shape their
      learning environments, which could alleviate some of the time and resource
      pressures in surgical training. The purpose of this study was to investigate the
      effects of self-directed or prescribed practice schedules (random or blocked) on
      learning suturing skills. METHODS: Participants watched an instructional video
      for simple interrupted, vertical mattress and horizontal mattress suturing then
      completed a pretest to assess baseline skills. Participants were assigned to 1 of
      4 practice groups: self-directed practice schedule, prescribed blocked practice
      schedule, prescribed random practice schedule or matched to the self-directed
      group (control). Practice of the skill was followed by a delayed (1 h) posttest.
      Improvement from pretest to posttest was determined based on differences in
      performance time and expert-based assessments. RESULTS: Analyses revealed a
      significant effect of group for difference in performance time of the simple
      interrupted suture. Random practice did not show the expected advantage for skill
      learning, but there was an advantage of self-directed practice. CONCLUSION: Self
      directed practice schedules may be desirable for optimal learning of simple
      technical skills, even when expert instruction is available. Instructors must
      also take into account the interaction between task difficulty and conditions of
      practice to develop ideal training environments.

PMID- 24284154
TI  - Patterns of use and outcomes for radiation therapy in the Quality Initiative in
      Rectal Cancer (QIRC) trial.
AB  - BACKGROUND: The Quality Initiative in Rectal Cancer (QIRC) trial targeted surgeon
      intraoperative technique and not radiation therapy (RT) use. We performed a post
      hoc analysis of RT use among patients in the QIRC trial, not by arm of trial but
      rather for the entire group. We wished to identify associations between local
      recurrence risk and use of preoperative, postoperative or no RT. METHODS: We
      compared demographic, tumour and process of care measures among patients
      receiving preoperative, postoperative or no RT. A multivariable Cox regression
      model assessed local recurrence risk. RESULTS: The QIRC trial enrolled 1015
      patients at 16 hospitals between 2002 and 2004. Radiation therapy use did not
      differ between trial arms, and median follow-up was 3.6 years. For the
      preoperative, postoperative and no RT groups, respectively, the percentage of
      patients was 12.8%, 19.3% and 67.9%; the percentage of stage II/III tumours was
      57.0%, 88.7% and 48.1%; and the local recurrence rate was 5.3%, 10.2% and 5.5% (p
      = 0.05). After controlling for patient and tumour characteristics, including
      tumour stage, the hazard ratio (HR) for local recurrence was increased in the
      postoperative RT versus the no RT group (HR 1.64, 95% confidence interval 1.04
      2.58, p = 0.027). CONCLUSION: Use of preoperative RT was low; most patients with
      stage II/III disease did not receive RT and, as expected, the postoperative RT
      group had the highest risk of local recurrence. Our results suggest opportunities
      to improve rectal cancer RT use in Ontario.

PMID- 24284155
TI  - Timeliness in obtaining emergent percutaneous procedures in severely injured
      patients: how long is too long and should we create quality assurance guidelines?
AB  - BACKGROUND: Modern trauma care relies heavily on nonoperative, emergent
      percutaneous procedures, particularly in patients with splenic, pelvic and
      hepatic injuries. Unfortunately, specific quality measures (e.g., arrival to
      angiography times) have not been widely discussed. Our objective was to evaluate
      the time interval from arrival to initiation of emergent percutaneous procedures
      in severely injured patients. METHODS: All severely injured trauma patients
      (injury severity score [ISS] > 12) presenting to a level 1 trauma centre (2007
      2010) were analyzed with standard statistical methodology. RESULTS: Among 60
      severely injured patients (mean ISS 31, hypotension 18%, mortality 12%), the
      median time interval to the initiation of an angiographic procedure was 270
      minutes. Of the procedures performed, 85% were therapeutic embolizations and 15%
      were diagnostic procedures. Splenic (median time 243 min, range 32-801 min) and
      pelvic (median time 278 min, range 153-466 min) embolizations accounted for 43%
      and 25% of procedures, respectively. The median embolization procedure duration
      for the spleen was 28 (range 15-153) minutes compared with 59 (range 34-171)
      minutes for the pelvis. Nearly 22% of patients required both an emergent
      percutaneous and subsequent operative procedure. Percutaneous therapy typically
      preceded open operative explorations. CONCLUSION: The time interval from arrival
      at the trauma centre to emergent percutaneous procedures varied widely. Improved
      processes emphasizing patient transition from the trauma bay to the angiography
      suite are essential. Discussion regarding the appropriate time to angiography is
      needed so this marker can be used as a quality outcome measure for all level 1
      trauma centres.

PMID- 24284156
TI  - Comparison of laparoscopic Roux-en-Y gastric bypass with laparoscopic sleeve
      gastrectomy for morbid obesity or type 2 diabetes mellitus: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most
      widely used bariatric procedures, and laparoscopic sleeve gastrectomy (LSG) as a
      single-stage procedure for treating morbid obesity is becoming more popular. We
      compared both techniques to evaluate their efficacy in treating morbid obesity or
      type 2 diabetes mellitus (T2DM). METHODS: We searched the Cochrane Controlled
      Trials Register databases, Medline, Embase, ISI databases and the Chinese
      Biomedical Literature Database to identify randomized controlled trials (RCTs) of
      LRYGB and LSG for morbid obesity or T2DM published in any language. Statistical
      analyses were carried out using RevMan software. RESULTS: Five worldwide RCTs
      with 196 patients in the LRYGB group and 200 in the LSG group were included in
      our analysis. Compared with patients who had LSG, those who had LRYGB had a
      higher remission rate of T2MD, lost more weight and had lower low-density
      lipoprotein, triglycerides, homeostasis model assessment index and insulin
      levels. There was no difference in the reoperation rate between the groups.
      However, patients treated with LRYGB had a higher incidence of complication than
      those treated with LSG. CONCLUSION: Our meta-analysis demonstrates that LRYGB is
      more effective than LSG for the surgical treatment of T2DM and control of
      metabolic syndrome. However, LSG is safer and has a reduced rate of
      complications. Further high-quality RCTs with long follow-up periods are needed
      to provide more reliable evidence.

PMID- 24284157
TI  - Outcomes: wedge resection versus lobectomy for non-small cell lung cancer at the
      Cancer Centre of Southeastern Ontario 1998-2009.
AB  - BACKGROUND: Sublobar resection for non-small cell lung cancer (NSCLC) remains
      controversial owing to concern about local recurrence and long-term survival
      outcomes. We sought to determine the efficacy of wedge resection as an
      oncological procedure. METHODS: We analyzed the outcomes of all patients with
      NSCLC undergoing surgical resection at the Cancer Centre of Southeastern Ontario
      between 1998 and 2009. The standard of care for patients with adequate
      cardiopulmonary reserve was lobectomy. Wedge resection was performed for patients
      with inadequate reserve to tolerate lobectomy. Predictors of recurrence and
      survival were assessed. Appropriate statistical analyses involved the chi(2)
      test, an independent samples t test and Kaplan-Meier estimates of survival.
      Outcomes were stratified for tumour size and American Joint Committee on Cancer
      seventh edition TNM stage for non-small cell lung cancer. RESULTS: A total of 423
      patients underwent surgical resection during our study period: wedge resection in
      71 patients and lobectomy in 352. The mean age of patients was 64 years. Mean
      follow-up for cancer survivors was 39 months. There was no significant difference
      between wedge resection and lobectomy for rate of tumour recurrence, mortality or
      disease-free survival in patients with stage IA tumours less than 2 cm in
      diameter. CONCLUSION: Wedge resection with lymph node sampling is an adequate
      oncological procedure for non-small cell lung cancer in properly selected
      patients, specifically, those with stage IA tumours less than 2 cm in diameter.

PMID- 24284158
TI  - Is the culture of surgery still a gender issue?

PMID- 24284159
TI  - Is the culture of surgery still a gender issue?; the authors respond.

PMID- 24284160
TI  - Comment on "comparison of the major intraoperative and postoperative
      complications between unilateral and sequential bilateral total knee arthroplasty
      in a high-volume community hospital".

PMID- 24284161
TI  - Comment on "comparison of the major intraoperative and postoperative
      complications between unilateral and sequential bilateral total knee arthroplasty
      in a high-volume community hospital"; the authors respond.

PMID- 24284163
TI  - Can we increase public awareness without creating anxiety about corona viruses?

PMID- 24284164
TI  - Clinician assessment, advice and referral for multiple health risk behaviors:
      prevalence and predictors of delivery by primary health care nurses and allied
      health professionals.
AB  - OBJECTIVE: Primary care clinicians have considerable potential to provide
      preventive care. This study describes their preventive care delivery. METHODS: A
      survey of 384 community health nurses and allied health clinicians from in New
      South Wales, Australia was undertaken (2010-11) to examine the assessment of
      client risk, provision of brief advice and referral/follow-up regarding smoking
      inadequate fruit and vegetable consumption, alcohol misuse, and physical
      inactivity; the existence of preventive care support strategies; and the
      association between supports and preventive care provision. RESULTS: Preventive
      care to 80% or more clients was least often provided for referral/follow-up (24.7
      45.6% of clinicians for individual risks, and 24.2% for all risks) and most often
      for assessment (34.4-69.3% of clinicians for individual risks, and 24.4% for all
      risks). Approximately 75% reported having 9 or fewer of 17 supports. Provision of
      care was associated with: availability of a paper screening tool; training; GP
      referral letter; and number of supports. CONCLUSION: The delivery of preventive
      care was limited, and varied according to type of care and risk. Supports were
      variably associated with elements of preventive care. PRACTICE IMPLICATIONS:
      Further research is required to increase routine preventive care delivery and the
      availability of supports.

PMID- 24284165
TI  - Free energy landscapes for initiation and branching of protein aggregation.
AB  - Experiments on artificial multidomain protein constructs have probed the early
      stages of aggregation processes, but structural details of the species that
      initiate aggregation remain elusive. Using the associative-memory, water
      mediated, structure and energy model known as AWSEM, a transferable coarse
      grained protein model, we performed simulations of fused constructs composed of
      up to four copies of the Titin I27 domain or its mutant I27* (I59E). Free energy
      calculations enable us to quantify the conditions under which such multidomain
      constructs will spontaneously misfold. Consistent with experimental results, the
      dimer of I27 is found to be the smallest spontaneously misfolding construct. Our
      results show how structurally distinct misfolded states can be stabilized under
      different thermodynamic conditions, and this result provides a plausible link
      between the single-molecule misfolding experiments under native conditions and
      aggregation experiments under denaturing conditions. The conditions for
      spontaneous misfolding are determined by the interplay among temperature,
      effective local protein concentration, and the strength of the interdomain
      interactions. Above the folding temperature, fusing additional domains to the
      monomer destabilizes the native state, and the entropically stabilized amyloid
      like state is favored. Because it is primarily energetically stabilized, the
      domain-swapped state is more likely to be important under native conditions. Both
      protofibril-like and branching structures are found in annealing simulations
      starting from extended structures, and these structures suggest a possible
      connection between the existence of multiple amyloidogenic segments in each
      domain and the formation of branched, amorphous aggregates as opposed to linear
      fibrillar structures. 

PMID- 24284167
TI  - Nourishing archaeology and science.

PMID- 24284166
TI  - Mechanism for the catastrophe-promoting activity of the microtubule destabilizer
      Op18/stathmin.
AB  - Regulation of microtubule dynamic instability is crucial for cellular processes,
      ranging from mitosis to membrane transport. Stathmin (also known as oncoprotein
      18/Op18) is a prominent microtubule destabilizer that acts preferentially on
      microtubule minus ends. Stathmin has been studied intensively because of its
      association with multiple types of cancer, but its mechanism of action remains
      controversial. Two models have been proposed. One model is that stathmin promotes
      microtubule catastrophe indirectly, and does so by sequestering tubulin; the
      other holds that stathmin alters microtubule dynamics by directly destabilizing
      growing microtubules. Stathmin's sequestration activity is well established, but
      the mechanism of any direct action is mysterious because stathmin binds to
      microtubules very weakly. To address these issues, we have studied interactions
      between stathmin and varied tubulin polymers. We show that stathmin binds tightly
      to Dolastatin-10 tubulin rings, which mimic curved tubulin protofilaments, and
      that stathmin depolymerizes stabilized protofilament-rich polymers. These
      observations lead us to propose that stathmin promotes catastrophe by binding to
      and acting upon protofilaments exposed at the tips of growing microtubules.
      Moreover, we suggest that stathmin's minus-end preference results from
      interactions between stathmin's N terminus and the surface of alpha-tubulin that
      is exposed only at the minus end. Using computational modeling of microtubule
      dynamics, we show that these mechanisms could account for stathmin's observed
      activities in vitro, but that both the direct and sequestering activities are
      likely to be relevant in a cellular context. Taken together, our results suggest
      that stathmin can promote catastrophe by direct action on protofilament structure
      and interactions. 

PMID- 24284168
TI  - Fit and resistant is a worst case scenario with bacterial pathogens.

PMID- 24284169
TI  - Genome-wide analysis of histone marks identifying an epigenetic signature of
      promoters and enhancers underlying cardiac hypertrophy.
AB  - Cardiac hypertrophy, initially an adaptive response of the myocardium to stress,
      can progress to heart failure. The epigenetic signature underlying this
      phenomenon is poorly understood. Here, we report on the genome-wide distribution
      of seven histone modifications in adult mouse cardiomyocytes subjected to a
      prohypertrophy stimulus in vivo. We found a set of promoters with an epigenetic
      pattern that distinguishes specific functional classes of genes regulated in
      hypertrophy and identified 9,207 candidate active enhancers whose activity was
      modulated. We also analyzed the transcriptional network within which these
      genetic elements act to orchestrate hypertrophy gene expression, finding a role
      for myocyte enhancer factor (MEF)2C and MEF2A in regulating enhancers. We propose
      that the epigenetic landscape is a key determinant of gene expression
      reprogramming in cardiac hypertrophy and provide a basis for understanding the
      role of chromatin in regulating this phenomenon. 

PMID- 24284170
TI  - Dual defensin strategy for targeting Enterococcus faecalis.

PMID- 24284171
TI  - A symbiotic relationship between epithelial and stromal stem cells.

PMID- 24284173
TI  - Sliding heavy stones to the Forbidden City on ice.

PMID- 24284172
TI  - Maurer's clefts, the enigma of Plasmodium falciparum.
AB  - Plasmodium falciparum, the causative agent of malaria, completely remodels the
      infected human erythrocyte to acquire nutrients and to evade the immune system.
      For this process, the parasite exports more than 10% of all its proteins into the
      host cell cytosol, including the major virulence factor PfEMP1 (P. falciparum
      erythrocyte surface protein 1). This unusual protein trafficking system involves
      long-known parasite-derived membranous structures in the host cell cytosol,
      called Maurer's clefts. However, the genesis, role, and function of Maurer's
      clefts remain elusive. Similarly unclear is how proteins are sorted and how they
      are transported to and from these structures. Recent years have seen a large
      increase of knowledge but, as yet, no functional model has been established. In
      this perspective we review the most important findings and conclude with
      potential possibilities to shed light into the enigma of Maurer's clefts.
      Understanding the mechanism and function of these structures, as well as their
      involvement in protein export in P. falciparum, might lead to innovative control
      strategies and might give us a handle with which to help to eliminate this deadly
      parasite. 

PMID- 24284175
TI  - Role for neuronal nitric oxide synthase in sleep homeostasis and arousal.

PMID- 24284174
TI  - Chordin forms a self-organizing morphogen gradient in the extracellular space
      between ectoderm and mesoderm in the Xenopus embryo.
AB  - The vertebrate body plan follows stereotypical dorsal-ventral (D-V) tissue
      differentiation controlled by bone morphogenetic proteins (BMPs) and secreted BMP
      antagonists, such as Chordin. The three germ layers--ectoderm, mesoderm, and
      endoderm--are affected coordinately by the Chordin-BMP morphogen system. However,
      extracellular morphogen gradients of endogenous proteins have not been directly
      visualized in vertebrate embryos to date. In this study, we improved
      immunolocalization methods in Xenopus embryos and analyzed the distribution of
      endogenous Chordin using a specific antibody. Chordin protein secreted by the
      dorsal Spemann organizer was found to diffuse along a narrow region that
      separates the ectoderm from the anterior endoderm and mesoderm. This Fibronectin
      rich extracellular matrix is called "Brachet's cleft" in the Xenopus gastrula and
      is present in all vertebrate embryos. Chordin protein formed a smooth gradient
      that encircled the embryo, reaching the ventral-most Brachet cleft. Depletion
      with morpholino oligos showed that this extracellular gradient was regulated by
      the Chordin protease Tolloid and its inhibitor Sizzled. The Chordin gradient, as
      well as the BMP signaling gradient, was self-regulating and, importantly, was
      able to rescale in dorsal half-embryos. Transplantation of Spemann organizer
      tissue showed that Chordin diffused over long distances along this signaling
      highway between the ectoderm and mesoderm. Chordin protein must reach very high
      concentrations in this narrow region. We suggest that as ectoderm and mesoderm
      undergo morphogenetic movements during gastrulation, cells in both germ layers
      read their positional information coordinately from a single morphogen gradient
      located in Brachet's cleft.

PMID- 24284176
TI  - Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell
      Morell receptor.
AB  - The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen
      remodeling of host glycoproteins by neuraminidase in the bloodstream and
      mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism
      of host protection by the AMR during the onset of sepsis and in response to the
      desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus
      pneumoniae. We find that the AMR selects among potential glycoprotein ligands
      unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate
      from blood circulation host factors that contribute to coagulation and
      thrombosis. This protection is attributable in large part to the rapid induction
      of a moderate thrombocytopenia by the AMR. We further show that neuraminidase
      activity in the blood can be manipulated to induce the clearance of AMR ligands
      including platelets, thereby preactivating a protective response in pneumococcal
      sepsis that moderates the severity of disseminated intravascular coagulation and
      enables host survival. 

PMID- 24284177
TI  - Linear aggregation of proteins on the membrane as a prelude to membrane
      remodeling.
AB  - Adhesion and insertion of curvature-mediating proteins can induce dramatic
      structural changes in cell membranes, allowing them to participate in several key
      cellular tasks. The way proteins interact to generate curvature remains largely
      unclear, especially at early stages of membrane remodeling. Using a coarse
      grained model of Bin/amphiphysin/Rvs domain with an N-terminal helix (N-BAR)
      interacting with flat membranes and vesicles, we demonstrate that at low protein
      surface densities, binding of N-BAR domain proteins to the membrane is followed
      by a linear aggregation and the formation of meshes on the surface. In this
      process, the proteins assemble at the base of emerging membrane buds. Our work
      shows that beyond a more straightforward scaffolding mechanism at high bound
      densities, the interplay of anisotropic interactions and the local stress imposed
      by the N-BAR proteins results in deep invaginations and endocytic vesicular bud
      like deformations, an order of magnitude larger than the size of the individual
      protein. Our results imply that by virtue of this mechanism, cell membranes may
      achieve rapid local increases in protein concentration. 

PMID- 24284178
TI  - Midlife trends in activities and disability.
AB  - OBJECTIVES: This is the first analysis that demonstrates empirically the likely
      tie between activities (time spent) and disability (health-related difficulty in
      activities). We compare trends in activities and disability for Americans ages 55
      to 69 in recent years, and assess cross-sectional linkages of activities and
      disability. METHODS: Data are from the Health and Retirement Study, a
      longitudinal survey of community-dwelling U.S. adults. Trends are estimated by
      mixed-effects regression models (MRMs) with time, age, and time-age interaction
      predictors. Links of activities and disability also use MRM. RESULTS: For midlife
      adults, hobbies/leisure and sports/exercise increased, repairs/yard decreased,
      and several activities had convex patterns; by contrast, disability prevalence
      was stable. Personal care hours rise with disability, but most activities
      decline. DISCUSSION: Activities are more dynamic than disability, and time use is
      associated with disability. Taken together, the results encourage broader
      activities in disability measures to capture better disability's scope and
      dynamics.

PMID- 24284179
TI  - Exploring the experiences of people with mild cognitive impairment and their
      caregivers with particular reference to healthcare - a qualitative study.
AB  - BACKGROUND: The aim of this study was to investigate the experiences of people
      with mild cognitive impairment (MCI; PWMCI) and their "advocates," particularly
      within healthcare services. METHODS: Semi-structured interviews were conducted
      with 23 PWMCI diagnosed <=6 months ago and 20 advocates recruited via patients.
      The resulting data were content-analyzed. RESULTS: PWMCI interviewed rarely
      reported negative impressions of their general practitioner (GP). Reports
      regarding memory services were more mixed: positive impressions related to
      finding the service to be "well run" and the staff "pleasant," negative ones to
      the assessment process or a perceived lack of feedback. Aside from improved
      information provision, most PWMCI had no suggestions for improvements to their
      healthcare. However, these results should be interpreted with caution as many of
      the PWMCI interviewed displayed evidence of impaired recall and/or insight
      relating to their condition and healthcare. Advocates generally reported more
      negative impressions of both contact with the PWMCI's GP (most commonly reporting
      a "dismissive" attitude) and memory services (with common complaints relating to
      the assessments used in clinics and lengthy waiting times). This group generally
      had suggestions for improvements to services - particularly regarding information
      provision, changes in the assessment process, and improvements in communication
      by services. CONCLUSIONS: To our knowledge, this is the first in-depth study of
      the difficulties experienced by PWMCI and their advocates which includes the
      context of healthcare provision. The specific needs of these groups, as described
      here, as well as those of people with dementia, should be considered when
      designing memory clinics and other related services.

PMID- 24284180
TI  - [China guiding outline on cardiovascular disease prevention].

PMID- 24284181
TI  - [Impact of insulin resistance on prognosis in non-diabetic patients with acute
      coronary syndromes].
AB  - OBJECTIVE: To evaluate the impact of insulin resistance (IR) on prognosis in non
      diabetic acute coronary syndrome patients. METHODS: In this prospective study, we
      enrolled 332 non-diabetic patients suffering from acute coronary syndrome. The
      patients were divided into three groups by HOMA-IR which calculated by formula:
      low HOMA-IR group (HOMA-IR < 2), 44 cases; moderate HOMA-IR group (2 <= HOMA2-IR
      < 6), 99 cases; high HOMA-IR group (HOMA >= 6) with HOMA index, 179 cases. The in
      hospital medical records of patients were compared, and all patients were
      followed up for one year after discharge. RESULTS: Incidence of hypertension (P =
      0.013), dyslipidemia (P < 0.001), faster resting heart rate (P < 0.001) and
      number of triple vessel coronary artery disease (P = 0.017) in high HOMA-IR group
      were significantly higher than in low and moderate HOMA-IR group. During follow
      up, the major end-point events increased in proportion to IR grade: 64.3% (26/44)
      in the high HOMA-IR group, 54.7% (52/99) in moderate HOMA-IR group and 41.3%
      (74/199) in low HOMA-IR group (P = 0.034). Multivariable logistic regression
      analysis showed that high sensitivity C reactive protein (OR = 1.012, 95%CI:1.002
      1.022, P = 0.022), HOMA-IR (OR = 1.250, 95%CI:1.043-1.497, P = 0.015) , triple
      vessel coronary artery disease (OR = 5.914, 95%CI:2.947-11.868, P < 0.001) ,
      ischemic changes on ECG (OR = 5.495, 95%CI:2.925-10.324, P < 0.001) and low left
      ventricular ejection fraction (LVEF <= 40%) (OR = 13.205, 95%CI:5.000-34.661, P <
      0.001) were independent risk factor for major end-point events during follow-up.
      CONCLUSIONS: Increased insulin resistance is linked with poor prognosis of non
      diabetic patients with acute coronary syndrome.

PMID- 24284182
TI  - [Relationship between estimated glomerular filtration rate level and clinical
      characteristics and outcome in patients with angiographic coronary artery disease
      and normal serum creatinine].
AB  - OBJECTIVE: To explore the relationship between estimated glomerular filtration
      rate level and clinical characteristics and outcome in coronary artery disease
      (CAD) patients with normal serum creatinine. METHOD: A total of 548 hospitalized
      and angiographic CAD patients with normal fasting serum creatinine were enrolled.
      The kidney function was estimated by using the abbreviated modification of diet
      in renal disease (MDRD) study equation. Patients were divided into three groups
      according to eGFR tertiles: high eGFR group (eGFR > 88.15 ml*min(-1)*1.73 m(-2),
      n = 184); intermediate group ZU(70.30 ml* min(-1)*1.73 m(-2) < eGFR <= 88.15
      ml*min(-1)*1.73 m(-2), n = 187); low eGFR group (eGFR <= 70.30 ml * min(-1)*1.73
      m(-2), n = 177). Clinical data and cardiovascular risk factors were recorded
      after admission and during (14.02 +/- 8.31) months follow up. The primary end
      point was combined major adverse cardiovascular and cerebral events (MACCE)
      including death, targeted vascular revascularization, non-fatal myocardial
      infarction, rehospitalization due to unstable angina and heart failure, and
      transient ischemic attack (TIA) and stroke. RESULTS: Patients in intermediate and
      low eGFR groups were older, more males, had more severe coronary artery disease,
      higher level of hsCRP, higher incidence of hypertension, and lower smoking rate
      than those in high eGFR group (all P < 0.05). A total of 89 MACCE were recorded
      during follow up. The level of eGFR was significantly lower in patients with
      MACCE than patients without MACCE [(73.76 +/- 19.81) ml*min(-1)*1.73 m(-2) vs.
      (84.97 +/- 23.42) ml*min(-1)*1.73 m(-2), P < 0.05]. Univariate and multivariate
      Cox regression analysis showed that eGFR was an independent predictor of MACCE in
      patients with CAD (univariate analysis: RR = 0.99, 95%CI:0.973-0.997, P < 0.05;
      multivariate analysis: RR = 0.98, 95%CI:0.976-0.998, P < 0.05). Kaplan-Meier
      survival analysis suggested that patients with low eGFR was linked with a
      decreased event free survival ratio (log-rank chi(2) = 7.271, P < 0.05).
      CONCLUSIONS: eGFR level in CAD patients with normal serum creatinine is
      associated with coronary artery severity, inflammation level and serves as an
      independent predictor for MACCE in this patient cohort.

PMID- 24284183
TI  - [Impacts of establishment of chest pain center on the door-to-balloon time and
      the short-term outcome after primary percutaneous coronary intervention of
      patients with ST segment elevated myocardial infarction].
AB  - OBJECTIVE: To investigate the impact of the establishment of chest pain center
      (CPC) model based on the pre-hospital real-time tele-12-lead electrocardiogram on
      the door-to-balloon (D-to-B) time and short-term outcome after primary
      percutaneous coronary intervention (PPCI) of patients with ST-segment elevated
      myocardial infarction (STEMI). METHODS: A regular CPC was established with pre
      hospital transmitted real-time 12-lead electrocardiogram system for pre-hospital
      diagnosis of STEMI and enabled the STEMI patients to bypass the emergency room
      and directly treated in the catheter lab to shorten the D-to-B time. The mean D
      to-B time, the short-term outcome and medical costs were compared in PPCI
      patients before (93 cases, group A) and after (149 cases, group B) the
      establishment of CPC. RESULTS: After the establishment of CPC, the annual mean D
      to-B time was significantly shortened [(127 +/- 79) min in group A vs.(72 +/- 23
      )min in group B, P < 0.01], the shortest monthly mean D-to-B time was remarkably
      reduced in group B than in group A [(56 +/- 11) min vs. (73 +/- 14) min, P <
      0.01]. The annual ratio of D-to-B below 90 minutes was significantly increased
      from 62.4% (58/93) in group A to 91.9% (137/149) in group B (P < 0.05) . The in
      hospital mortality rate tended to be lower and the incidence of heart failure
      during hospitalization was significantly reduced in group B compared with group A
      [3.4% (5/149) vs. 6.5% (6/93), P > 0.05; 14.1% (21/149) vs. 24.7% (23/93), P <
      0.05]. The length of hospital stay was slightly shortened from (8.98 +/- 4.89)
      days to (7.79 +/- 5.43) days (P > 0.05). Corrected mean medical cost went down by
      9.4% (P < 0.05). CONCLUSION: The establishment of CPC may significantly shorten
      the D-to-B time, improve the short-term outcome and reduce the hospitalization
      cost for PPCI patients with STEMI.

PMID- 24284184
TI  - [Types and risk factors of arrhythmia on young patients with acute coronary
      syndrome in Henan province].
AB  - OBJECTIVE: The types and risk factors of arrhythmia were analyzed on acute
      coronary syndrome (ACS) patients under the age of 44 years who were hospitalized
      in Henan province between September 2009 to June 2012. METHODS: Medical records
      of eligible patients were obtained from the information system of the First
      Affiliated Hospital of Zhengzhou University teleconsultation information center.
      Middle aged and elderly ACS patients who were hospitalized at the same period
      served as controls. Data on arrhythmia types, blood pressure, thyroid disease,
      respiratory sleep apnea syndrome, smoking history, history of alcohol
      consumption, eating habits, family history of early-onset arrhythmia, laboratory
      tests were analyzed. RESULTS: (1) Arrhythmia was detected in 110 out of young ACS
      patients (55%), which was significantly lower than that in the elderly ACS
      patients (71.05%, P < 0.01). (2) The top three arrhythmias in young ACS patients
      were: sinus tachycardia (30.50%), the premature ventricular contractions
      (19.00%), atrial flutter/atrial fibrillation (16.50%). Incidence of sinus
      tachycardia, atrial flutter/atrial fibrillation were significantly higher while
      incidence of ventricular tachycardia, ventricular fibrillation, paroxysmal
      supraventricular tachycardia were significantly lower in young ACS patients than
      in middle-aged ACS patients (all P < 0.05). The incidence of sinus tachycardia
      was higher while incidence of ventricular premature accelerated ventricular
      spontaneous cardiac rhythm, ventricular tachycardia, ventricular fibrillation,
      non-paroxysmal supraventricular tachycardia, atrial flutter/atrial fibrillation,
      paroxysmal supraventricular tachycardia, sinus bradycardia, nodal escape,
      atrioventricular block were significantly lower in young ACS patients than in
      elderly ACS patients (all P < 0.05). (3) Body mass index, incidence of smoking,
      coronary three-vessel disease, drinking, eating salty foods, thyroid dysfunction,
      sleep apnea were significantly higher in youth ACS patients with arrhythmia than
      in young ACS patients without arrhythmia (all P < 0. 05). (4) Logistic regression
      analysis found that number of diseased coronary vessels (OR = 24.293), smoking
      (OR = 1.112) and alcohol consumption (OR = 1.039) were independent risk factor
      for developing arrhythmia in young ACS patients from Henan province. CONCLUSIONS:
      The main types of arrhythmia are sinus tachycardia, premature ventricular
      contractions, atrial flutter/atrial fibrillation and the major risk factors
      related to the arrhythmia are number of diseased coronary vessels, smoking and
      alcohol consumption in young ACS patients from Henan province.

PMID- 24284185
TI  - [Safety and feasibility of carotid artery stenting in patients with coexisting
      carotid and coronary artery disease].
AB  - OBJECTIVE: To evaluate the safety and feasibility of carotid artery stenting
      (CAS) for treating patients with coexisting carotid and coronary artery disease.
      METHODS: The clinical data of 237 consecutive patients [(66.1 +/- 7.7) years old,
      79.7% male] with coexisting carotid and coronary artery disease undergoing CAS in
      Fuwai hospital from January 2005 to June 2010. The patients were analyzed
      retrospectively.Indication for CAS was defined as carotid artery diameter
      reduction of > 60% (symptomatic) or > 80% (asymptomatic) with suitable carotid
      artery anatomy for stenting. Thirty-day rates of stroke, death and myocardial
      infarction after CAS were assessed. RESULTS: All patients suffered from coronary
      artery disease, of whom 87(36.7%) had unstable angina pectoris and 82(34.6%) had
      recent myocardial infarction (< 30 days). The procedural success rate of CAS was
      99.2 % (235/237). Cerebral protection devices were used in 234 patients (99.6%).
      Among them, 36(15.2%) patients received simultaneous bilateral CAS and 79(33.3%)
      patients underwent simultaneous percutaneous intervention of other non-coronary
      arteries.Within 30 days after CAS, 127(53.6%) patients underwent coronary
      revascularization, including 118(49.6%) coronary artery bypass grafting and 9
      (3.8%) percutaneous coronary intervention. The rate of major stroke, minor
      stroke, death and myocardial infarction from time of CAS to 30 days was 2.1%
      (5/237), 3.0% (7/237),0.4% (1/237) and 0.4% (1/237) respectively. CONCLUSION:
      Data from this study indicate that CAS is safe and feasible for treating patients
      with coexisting carotid and coronary artery disease with a low incidence of
      periprocedural complication rate.

PMID- 24284186
TI  - [Correlation between plasma aldosterone concentration and left ventricular
      structure in hypertensive patients].
AB  - OBJECTIVE: To observe the correlation between plasma aldosterone concentration
      (PAC) and left ventricular structure in hypertensive patients. METHODS: A total
      of 201 hypertensive patients [117 male, aged from seventeen to sixty eight years
      old, mean (43.6 +/- 10.2) years] were included. All subjects underwent
      echocardiography examination for measurement of left ventricular end-diastolic
      dimension (LVEDD), LV posterior wall thickness (LVPWT), interventricular septum
      thickness (IVST) and LV mass index (LVMI). Plasma PAC was also measured at three
      postural positions. According to the sitting PAC, subjects were divided into high
      aldosterone group (PAC >= 120 ng/L, n = 83) and normal aldosterone (PAC < 120
      ng/L, n = 118) group. Bivariate correlation and multiple stepwise regression
      analysis were performed to analyze the correlation between left ventricular
      structure parameters and PAC. RESULTS: IVST, LVPWT values were significantly
      higher in the increased PAC group than that in normal PAC group [ (10.4 +/- 1.0)
      mm vs. (10.9 +/- 1.8) mm, (10.1 +/- 0.7) mm vs.(10.4 +/- 1.5) mm, all P < 0.05].
      Bivariate correlation analysis showed that PAC was weakly correlated with IVST (r
      = 0.190, P < 0.05) , while was not correlated to LVMI, LVPWT and LVEDD (all P >
      0.05). Multiple linear stepwise regression analysis showed that PAC was
      positively correlated with IVST and LVPWT (beta = 0.206 and beta = 0.241,
      respectively, all P < 0.05), but was not correlated to LVMI and LVEDD (all P >
      0.05). CONCLUSION: PAC is positively correlated with IVST and LVPWT in
      hypertensive patients.

PMID- 24284187
TI  - [Current status of morning blood pressure control and medication of hypertensive
      patients in Beijing].
AB  - OBJECTIVE: To explore the current status of morning blood pressure and medication
      of hypertensive patients in Beijing. METHODS: This study included 2187
      hypertensive patients who visited the ambulance of our cardiology department in
      the morning (7:00-10:00) from March 2012 to April 2012. Patients were divided
      into three groups: no antihypertensive agent group, single antihypertensive drug
      therapy group (include CCB, ARB, ACEI, beta-blocker) and combined drug therapy
      group at least one month. Blood pressure control rate was compared among the
      groups. RESULTS: Target blood pressure was not reached in 1193 patients (54.6%),
      most patients took CCB and the target blood pressure was not reached in 61.7%
      (295/478) patients taking CCB. There was no significant difference on target
      blood pressure uncontrolled rate among the four single drug subgroups (CCB, ARB,
      ACEI, beta-blocker). The blood pressure uncontrolled rate was 46.3% (63/136) for
      amlodipine, 70.5% (55/78) for nifedipine and 73.8% (31/42) for felodipine. There
      OR of uncontrolled blood pressure rate was 0.36 (amlodipine vs. nifedipine,
      95%CI:0.20-0.65) and 0.31% (amlodipine vs. felodipine, 95%CI:0.14-0.66).
      CONCLUSION: The morning blood pressure uncontrolled rate is high in hypertensive
      patients visiting Beijing tertiary hospitals. Amlodipine is possible superior to
      nifedipine and felodipine on morning blood pressure control in this patient
      cohort.

PMID- 24284188
TI  - [Clinical application of extracorporeal membrane oxygenation for treatment of
      adult refractory cardiogenic shock].
AB  - OBJECTIVE: To summarize the clinical experience of extracorporeal membrane
      oxygenation (ECMO) treatment for adult refractory cardiogenic shock. METHODS:
      From January 2003 to January 2011, patients with refractory cardiogenic shock
      required veno-arterial ECMO by failure of conventional therapy and intra-aortic
      balloon pump counterpulsation therapy were retrospectively studied. Patients with
      severe traumatic brain injury, advanced malignancies and multiple organ failure
      were excluded. Patients were divided into weaned group (n = 31) and not weaned
      group (n = 23) according to the ECMO weaning. RESULTS: The duration of ECMO was
      24.16 (14.12, 56.75) hours. Twenty-two out of 31 patients in the weaned group
      survived and were discharged, 9 patients died after successfully weaned from ECMO
      (5 due to multisystem organ failure, 2 due to reoccurred cardiogenic shock, 1 due
      to infectious shock and 1 due to disseminated or diffuse intravascular
      coagulation). Pre-ECMO mean arterial pressure, ejection fraction, the duration of
      ECMO were significantly higher while pre-ECMO blood lactate [(8.64 +/- 3.17) vs.
      (14.44 +/- 2.52) , P < 0.01], the duration of ROSC [ (16.70 +/- 5.29) vs. (35.64
      +/- 5.89), P < 0.01] and multisystem organ failure [0 vs. 17.4% (4/23) , P <
      0.05] were lower in weaned group than in not wean group. CONCLUSIONS: ECMO is an
      effective mechanical assistant therapy strategy for adult refractory cardiogenic
      shock patients. Timely applying this strategy on suitable patients is crucial for
      the success of ECMO. Cardiac function and reversibility of heart failure are key
      factors determine the fate of weaned or not weaned ECMO in adult refractory
      cardiogenic shock patients.

PMID- 24284189
TI  - [Clinical characterization of patients with Danon disease].
AB  - OBJECTIVE: To analyze the clinical characterization of Danon disease caused by
      the mutation of lysosome-associated membrane protein-2 (LAMP-2) gene. METHODS:
      The clinical features, serum biochemical index, electrocardiogram and
      echocardiography data were retrospectively reviewed in 5 patients with
      genetically confirmed Danon disease. Mean follow-up period was (56 +/- 6) months.
      RESULTS: Five patients including 2 men and 3 women in 2 unrelated families with 2
      novel mutations in the exon 3 (c.189-190TGdel) and 8 (c.1205Cdel) of the LAMP-2
      gene were identified. All patients had cardiomyopathy, 1 patient (1/5) had
      skeletal myopathy, and none of the patients had mental retardation. The two male
      patients presented cardiac symptoms at the age of 9 and 10 years, respectively,
      and all female patients were asymptomatic. Biochemical analysis showed that serum
      creatine kinase and liver transaminase enzyme were increased in 2 patients (2/5).
      Abnormal electrocardiogram was observed in all patients, and 2 patients (2/5) had
      ventricular preexcitation. During the follow-up. One male patient died of cardiac
      failure at the age of 18 years and three months, and the symptoms of the other
      male patients rapidly developed with the evolution from hypertrophic
      cardiomyopathy into dilated cardiomyopathy. However, all female patients remained
      asymptomatic, and repeat echocardiography indicated only mild ventricular
      hypertrophy during follow up. CONCLUSION: Patients with Danon disease mainly
      present hypertrophic cardiomyopathy, and sometimes presents with skeletal
      myopathy. The disorder occurs at early, age and progresses quickly and ends with
      poor prognosis in male patients. Other clinical features include elevations of
      serum creatine kinase and liver transaminase enzyme, ventricular preexcitation on
      electrocardiogram, and ventricular hypertrophy detected by echocardiography.
      Female patients remain asymptomatic till now in our cohort.

PMID- 24284190
TI  - [Clinical features and management of complete heart block after transaortic
      extended septal myectomy in patients with hypertrophic obstructive
      cardiomyopathy].
AB  - OBJECTIVE: To analyze the clinical features, precaution and management of
      complete heart block (CHB) after transaortic extended septal myectomy operation
      (extended Morrow procedure) in patients with hypertrophic obstructive
      cardiomyopathy (HOCM). METHODS: From October 1996 to December 2011, 10[6 men;
      mean age (45.4 +/- 15.8) years, range 13-60 years] out of 160 consecutive HOCM
      patients underwent extended Morrow procedure developed CHB postoperatively. Their
      clinical data were retrospectively analyzed. Baseline transthoracic
      echocardiography showed that the left ventricular outflow tract (LVOT) gradients
      was from 68 to 149 (105.1 +/- 25.9) mm Hg (1 mm Hg = 0.133 kPa), ECG showed right
      bundle branch block in 5 patients and atrial fibrillation, atrial premature beats
      or ST-T segment changes in other 5 patients. Besides extended Morrow procedure,
      concomitant surgical procedures included mitral valve replacement (MVR) in 2
      (2/10) and MVR plus coronary artery bypass grafting in another 2 (2/10) patients.
      Follow-up data were obtained by subsequent clinic visits in outpatient department
      and telephone interviews. RESULTS: The in-hospital mortality was 20% (these two
      patients died of low cardiac output syndrome and multiple organs failure). Four
      patients underwent MVR simultaneously survived the operation. Postoperative
      echocardiography demonstrated a reduced LVOT gradient[(13.6 +/- 9.7) mm Hg, P <
      0.001]. Permanent pacemakers were implanted in all 8 survived patients at 6 days
      to 7 months after operation. No other severe complications were observed. During
      follow-up [from 4 to 72 (19.4 +/- 22.1) months], there was no death, 1 patient
      readmitted to our center at 71 months post operation to change the pacemaker
      because of low voltage of previously implanted pacemaker. Physical capacity and
      quality of life improved significantly post operation in these 8 patients. The
      NYHA functional class remained at I-II post operation and during follow up.
      CONCLUSIONS: CHB is a severe complication after extended Morrow procedure for
      patients with HOCM and timely permanent pacemaker implantation is mandatory for
      patients with post procedure CHB.

PMID- 24284191
TI  - [Inflammation accelerates lipid dysregulation mediated cardiac fibrosis through
      enhancing myocardial endothelial-to-mesenchymal transition].
AB  - OBJECTIVE: Dyslipidemia and chronic inflammation are risk factors of cardiac
      fibrosis. This study was aimed to investigate their possible synergetic effects
      and underlying mechanisms on progression of cardiac fibrosis in apolipoprotein E
      knockout (ApoE -/-) mice. METHODS: Twenty-four ApoE-/- mice were divided into
      normal chow diet (control), high fat diet (HFD group), and HFD plus
      subcutaneously injection of 10% casein (inflammation group) for 8 weeks. Lipid
      profile and serum amyloid A (SAA) were examined by clinical biochemical assays
      and Enzyme-Linked Immunosorbent Assay, respectively. Hematoxylin-eosin staining
      (HE) and Masson staining were used to evaluate the myocardial accumulation of
      lipid and collagen. Collagen I protein expression was detected by
      immunohistochemical staining. Endothelial-to-mesenchymal transition related
      protein expressions were determined by Western blot. RESULTS: Serum SAA level was
      significantly higher in inflammation group [(127.42 +/- 26.99) ng/ml] than in
      control [(15.40 +/- 7.62) ng/ml] and HFD [(8.17 +/- 0.72) ng/ml] group (all P <
      0.01).However serum levels of triglyceride, total cholesterol, and low density
      lipoprotein (LDL) cholesterol were significantly higher in HFD group than in
      inflammation and control groups[TG (7.53 +/- 2.05) mmol/L vs. (3.43 +/- 0.79)
      mmol/L; TC (27.80 +/- 3.99) mmol/L vs. (14.94 +/- 1.92) mmol/L;LDL-C (11.56 +/-
      2.56) mmol/L vs. (9.46 +/- 1.31) mmol/L, all P < 0.05) . Foam cell formation in
      cardiac vessels, myocardial collagen deposit, protein expressions of collagen I,
      CD31, and alpha-smooth muscle actin (alpha-SMA) were all significantly higher in
      inflammation group than in HFD group (all P < 0.05) suggesting that inflammation
      contributes to the phenotype endothelial-to-mesenchymal transition in heart.
      CONCLUSION: Inflammation exacerbates dyslipidemia mediated cardiac fibrosis in
      ApoE-/- mice partly through enhancing myocardial endothelial-to-mesenchymal
      transition.

PMID- 24284192
TI  - [The optimal cut-off value of waist-to-height ratio for detecting severe central
      obesity and low body weight adult Chinese population].
AB  - OBJECTIVE: To explore the optimal cut-off values of waist-to-height ratio (WHtR)
      for detecting the severe central obesity and low body weight in adult Chinese
      population. METHODS: A total of 30 630 participants aged 35-59 years from
      different areas in mainland China were surveyed for cardiovascular diseases risk
      factors in two independent cross-sectional studies that carried out in 1992-1994
      and 1998, respectively. Indices, such as sensitivity, specificity for
      hypertension, abnormal glucose, high serum total cholesterol, low serum high
      density lipoprotein cholesterol and clustering of risk factors (number >= 2) were
      calculated to evaluate the efficacy individual cut-off point of WHtR. The cut-off
      point value for obvious central obesity was fixed on the point whose specificity
      of the point was gathered more than 90%. And the cut-off point value to indicate
      low weight was determined by the percentile distribution of WHtR, at which the
      5th percentile of point, both in male and female population. Based on the
      principle of convenient and practical for use, the optimal cut-off point values
      of WHtR for low weight and obvious central obesity were determined. RESULTS: The
      cut-off values of WHtR to detect severe central obesity were 0.54 and 0.57 for
      men and women, respectively. Additionally, the cut-off points of WHtR for each of
      the 4 cardiovascular risk factors to evaluate the severity separately ranged from
      0.54 to 0.55 in male, and ranged from 0.57 to 0.58 in female. The 5th percentile
      of WHtR, which was the point value of WHtR to indicate low body weight, was 0.40
      in both male and female population. CONCLUSION: Our data suggest that the optimal
      cut-off value of WHtR for defining severe central obesity and low body weight
      should be 0.57 and 0.40, respectively.

PMID- 24284193
TI  - [Association between blood pressure level and incidence of carotid artery plaque
      in middle-aged and elderly people].
AB  - OBJECTIVE: To explore the association between blood pressure level and incidence
      of carotid arterial plaque in middle-aged and elderly people. METHODS: A total of
      5852 individuals were randomly stratified from the 101 510 health examination
      survey participants in Tangshan Kailuan Company community during 2006-2007. A
      total of 5440 people (age above 40 years old, free of stroke, TIA and myocardial
      infarction) were enrolled in the final analysis. A questionnaire survey, blood
      biochemical analysis and carotid artery ultrasound examination were finished by
      trained medical staff. Sixteen individuals without carotid artery plaques
      information and 35 individuals without blood pressure information were excluded.
      Finally, a total of 5389 participants [3235 male, mean age: (54.7 +/- 11.8)
      years] were analyzed. According to 2010 Chinese guideline to prevention and
      treatment of hypertension and blood pressure level classification, participants
      were divided into normotensive group (n = 1377), high normal blood pressure group
      (n = 1971) and hypertensive group (n = 2041). Multivariate logistic regression
      analysis was used to determine the risk factors of the carotid artery plaques.
      RESULTS: Age, male gender, BMI, IMT, TG, FBG, smoking and alcohol drinking rate
      were significantly higher in high normal blood pressure group than in
      normotensive group (all P < 0.05), LDL-C, HDL-C, hs-CRP and TC were similar
      between these two groups. Incidence of carotid artery plaques in normotensive,
      high normal blood pressure and hypertensive groups was 24.8%, 37.4%, 60.2%
      respectively. The risk of carotid artery plaques was increased to 38% and 163% in
      high normal and hypertensive groups compared to normotensive group, the OR ratio
      was 1.38 (95%CI: 1.15-1.66) and 2.63 (95%CI: 2.18-3.18), respectively. After
      adjusting gender, age, smoking, alcohol consumption, TG, TC, HDL-C, FBG, hs-CRP
      and BMI, the risk of developing carotid artery plague was increased in proportion
      to increasing blood pressure and the OR value was 1.24 (95%CI:1.01-1.52) , 1.69
      (95%CI:1.34-2.15) and 2.66 (95%CI:2.20-3.21) in high normal group I [SBP/DBP 121
      129/80-84 mm Hg(1 mm Hg = 0.133 kPa)] and high normal group II (SBP/DBP 130
      139/85-89 mm Hg) and hypertensive group, respectively. CONCLUSIONS: The
      cardiovascular risk factors and prevalence of carotid artery plague increase in
      proportion to blood pressure level in this cohort. The detection rate of carotid
      artery plague is already significantly increased in individuals with high normal
      blood pressure.

PMID- 24284194
TI  - [A case of Churg-Strauss syndrome accompanied by coronary artery disease].

PMID- 24284195
TI  - [A case of arrhythmogenic right ventricular cardiomyopathy diagnosis suggested by
      electrocardiogram].

PMID- 24284196
TI  - [Research progress on cardiosphere-derived stem cells].

PMID- 24284197
TI  - [Crucial role of RhoA/ROCK pathway on modulating microenvironment after acute
      myocardial infarction].

PMID- 24284198
TI  - Why small and medium chemical companies continue to pose severe environmental
      risks in rural China.
AB  - In China, rural chemical SMEs are often believed to still largely operate below
      the sustainability radar. This paper investigates to what extent and how chemical
      SMEs are already experiencing pressure to improve their environmental
      performance, using an in-depth case study in Jasmine County, Hebei province. The
      results show that local residents had rather low trust in the environmental
      improvement promises made by the enterprises and the local government, and
      disagreed with the proposed improvement plans. Although the power of local
      residents to influence decision making remained limited, the chemical SMEs
      started to feel increasing pressures to clean up their business, from
      governments, local communities and civil society, and international value chain
      stakeholders. Notwithstanding these mounting pressures chemical SME's
      environmental behavior and performance has not changed radically for the better.
      The strong economic ties between local county governments and chemical SMEs
      continue to be a major barrier for stringent environmental regulation. 

PMID- 24284199
TI  - Synthesis rates and binding kinetics of matrix products in engineered cartilage
      constructs using chondrocyte-seeded agarose gels.
AB  - Large-sized cartilage constructs suffer from inhomogeneous extracellular matrix
      deposition due to insufficient nutrient availability. Computational models of
      nutrient consumption and tissue growth can be utilized as an efficient
      alternative to experimental trials to optimize the culture of large constructs;
      models require system-specific growth and consumption parameters. To inform
      models of the [bovine chondrocyte]-[agarose gel] system, total synthesis rate
      (matrix accumulation rate+matrix release rate) and matrix retention fractions of
      glycosaminoglycans (GAG), collagen, and cartilage oligomeric matrix protein
      (COMP) were measured either in the presence (continuous or transient) or absence
      of TGF-beta3 supplementation. TGF-beta3's influences on pyridinoline content and
      mechanical properties were also measured. Reversible binding kinetic parameters
      were characterized using computational models. Based on our recent nutrient
      supplementation work, we measured glucose consumption and critical glucose
      concentration for tissue growth to computationally simulate the culture of a
      human patella-sized tissue construct, reproducing the experiment of Hung et al.
      (2003). Transient TGF-beta3 produced the highest GAG synthesis rate, highest GAG
      retention ratio, and the highest binding affinity; collagen synthesis was
      elevated in TGF-beta3 supplementation groups over control, with the highest
      binding affinity observed in the transient supplementation group; both COMP
      synthesis and retention were lower than those for GAG and collagen. These results
      informed the modeling of GAG deposition within a large patella construct; this
      computational example was similar to the previous experimental results without
      further adjustments to modeling parameters. These results suggest that these
      nutrient consumption and matrix synthesis models are an attractive alternative
      for optimizing the culture of large-sized constructs. 

PMID- 24284201
TI  - Missed opportunities for person-centered communication: implications for staff
      resident interactions in long-term care.
AB  - BACKGROUND: Social interactions in long-term care settings between staff and
      residents with dementia have been characterized as task-oriented, patronizing,
      and/or overly directive. Long-term care settings can be contexts that emphasize
      dependency and threaten the personal identity of older residents. Yet, leaders in
      the long-term care sector have acknowledged recently that dementia care must move
      beyond the completion of caregiving tasks and adopt a person-centered approach.
      This approach involves caregivers incorporating a resident's life history and
      preferences during interactions. The objectives of this study were to examine the
      extent to which staff-resident communication is person-centered and the extent to
      which staff miss opportunities to communicate with residents in a person-centered
      manner. METHODS: Conversations (N = 46) of 13 staff-resident dyads were audio
      recorded during routine care tasks over 12 weeks. Staff utterances within these
      conversations were coded for person-centered communication and missed
      opportunities where person-centered communication could have been used. RESULTS:
      Findings revealed a common communication sequence where utterances coded as
      person-centered were followed by utterances coded as missed opportunities. This
      sequence suggests that the positive impact of person-centered communication may
      be undermined when such communication is followed by missed opportunities. Data
      also revealed that missed opportunities highlight the need for staff training.
      CONCLUSION: The findings underscore the importance of sustaining person-centered
      communication while completing routine care tasks.

PMID- 24284200
TI  - Transuretral resection of the bladder (TURB): analysis of complications using a
      modified Clavien system in an Italian real life cohort.
AB  - INTRODUCTION: To evaluate the applicability of a modified Clavien classification
      system (CCS) in grading postoperative complications of transurethral resection of
      bladder tumours (TURB). MATERIALS AND METHODS: A series of patients undergoing
      monopolar TURB from April 2011 to March 2012 at five Italian centers were
      enrolled. All complications occurring within the first 30-day postoperative
      period were prospectively recorded and graded according to the CCS. RESULTS:
      Overall, 275 patients were included. Median age was 71 (63/78) years; median BMI
      was 28 (25.4/30.8) Kg/m(2), median tumour size was 2 (1-3) cm; median number of
      tumour lesions was 1 (1-3). Median operative time was 30 (20/45) min. Fifty-seven
      complications were recorded in 43 patients. Overall postoperative morbidity rate
      was 16%. Most of the complications were not serious and classified as Clavien
      type I (42 cases; 74%) or II (8 cases, 14%). Higher grade complications were
      scarce: CCS IIIa in 1 case (2%) and CCS IIIb in six cases (10%). No TURB related
      death was reported. Six patients were re-operated due to significant bleeding or
      clot retention on postoperative days 2-7. On univariate (73.5 +/- 38 versus 36.7
      +/- 21.6 min) and multivariate analysis longer operative time was an independent
      predictor of complications (OR: 1.06 per min, 95%CI 1.04-1.08, p = 0.001).
      CONCLUSIONS: A modified CCS can be used as a standardized tool to objectively
      define the complications of TURB which confirms to be a safe procedure with a low
      surgical morbidity. This tool can be used to aid in patient counselling and to
      facilitate scientific assessment.

PMID- 24284202
TI  - The isolated N terminus of Ring1B is a well-folded, monomeric fragment with
      native-like structure.
AB  - The Polycomb group (PcG) proteins assemble into Polycomb repressive complexes
      (PRCs), PRC1 and PRC2, which act as general transcriptional repressors. PRC1
      comprises a variety of biochemical entities endowed with histone H2A
      monoubiquitylation activity conferred by really interesting new gene (RING)
      finger E3 ubiquitin ligases Ring1A and Ring1B. All PRC1 complexes contain Ring1
      proteins which are essential for Polycomb epigenetic regulation. We have been
      able to express the isolated N-terminal region of Ring1B, N-Ring1B, comprising
      the first 221 residues of the 334-residue-long Ring1B. This fragment contains the
      41-residue-long RING finger motif, and flanking sequences that form an
      interacting platform for PcG and non-PcG proteins. We found that the N-Ring1B is
      a well-folded, monomeric fragment, with native-like structure which unfolds
      irreversibly. The protein is capable of binding to an ubiquitin-conjugase protein
      (with an 85% of sequence similarity to the Ring1B physiological partner) with
      moderate affinity. 

PMID- 24284203
TI  - CCAAT/enhancer binding protein-mediated regulation of TGFbeta receptor 2
      expression determines the hepatoblast fate decision.
AB  - Human embryonic stem cells (hESCs) and their derivatives are expected to be used
      in drug discovery, regenerative medicine and the study of human embryogenesis.
      Because hepatocyte differentiation from hESCs has the potential to recapitulate
      human liver development in vivo, we employed this differentiation method to
      investigate the molecular mechanisms underlying human hepatocyte differentiation.
      A previous study has shown that a gradient of transforming growth factor beta
      (TGFbeta) signaling is required to segregate hepatocyte and cholangiocyte
      lineages from hepatoblasts. Although CCAAT/enhancer binding proteins (c/EBPs) are
      known to be important transcription factors in liver development, the
      relationship between TGFbeta signaling and c/EBP-mediated transcriptional
      regulation in the hepatoblast fate decision is not well known. To clarify this
      relationship, we examined whether c/EBPs could determine the hepatoblast fate
      decision via regulation of TGFbeta receptor 2 (TGFBR2) expression in the
      hepatoblast-like cells differentiated from hESCs. We found that TGFBR2 promoter
      activity was negatively regulated by c/EBPalpha and positively regulated by
      c/EBPbeta. Moreover, c/EBPalpha overexpression could promote hepatocyte
      differentiation by suppressing TGFBR2 expression, whereas c/EBPbeta
      overexpression could promote cholangiocyte differentiation by enhancing TGFBR2
      expression. Our findings demonstrated that c/EBPalpha and c/EBPbeta determine the
      lineage commitment of hepatoblasts by negatively and positively regulating the
      expression of a common target gene, TGFBR2, respectively.

PMID- 24284204
TI  - Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate
      specification in the adult olfactory bulb.
AB  - Meis homeodomain transcription factors control cell proliferation, cell fate
      specification and differentiation in development and disease. Previous studies
      have largely focused on Meis contribution to the development of non-neuronal
      tissues. By contrast, Meis function in the brain is not well understood. Here, we
      provide evidence for a dual role of the Meis family protein Meis2 in adult
      olfactory bulb (OB) neurogenesis. Meis2 is strongly expressed in neuroblasts of
      the subventricular zone (SVZ) and rostral migratory stream (RMS) and in some of
      the OB interneurons that are continuously replaced during adult life. Targeted
      manipulations with retroviral vectors expressing function-blocking forms or with
      small interfering RNAs demonstrated that Meis activity is cell-autonomously
      required for the acquisition of a general neuronal fate by SVZ-derived
      progenitors in vivo and in vitro. Additionally, Meis2 activity in the RMS is
      important for the generation of dopaminergic periglomerular neurons in the OB.
      Chromatin immunoprecipitation identified doublecortin and tyrosine hydroxylase as
      direct Meis targets in newly generated neurons and the OB, respectively.
      Furthermore, biochemical analyses revealed a previously unrecognized complex of
      Meis2 with Pax6 and Dlx2, two transcription factors involved in OB neurogenesis.
      The full pro-neurogenic activity of Pax6 in SVZ derived neural stem and
      progenitor cells requires the presence of Meis. Collectively, these results show
      that Meis2 cooperates with Pax6 in generic neurogenesis and dopaminergic fate
      specification in the adult SVZ-OB system.

PMID- 24284205
TI  - beta-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and
      elongation.
AB  - Non-canonical Wnt/planar cell polarity (PCP) signaling plays a primary role in
      the convergent extension that drives neural tube closure and body axis
      elongation. PCP signaling gene mutations cause severe neural tube defects (NTDs).
      However, the role of canonical Wnt/beta-catenin signaling in neural tube closure
      and NTDs remains poorly understood. This study shows that conditional gene
      targeting of beta-catenin in the dorsal neural folds of mouse embryos represses
      the expression of the homeobox-containing genes Pax3 and Cdx2 at the dorsal
      posterior neuropore (PNP), and subsequently diminishes the expression of the
      Wnt/beta-catenin signaling target genes T, Tbx6 and Fgf8 at the tail bud, leading
      to spina bifida aperta, caudal axis bending and tail truncation. We demonstrate
      that Pax3 and Cdx2 are novel downstream targets of Wnt/beta-catenin signaling.
      Transgenic activation of Pax3 cDNA can rescue the closure defect in the beta
      catenin mutants, suggesting that Pax3 is a key downstream effector of beta
      catenin signaling in the PNP closure process. Cdx2 is known to be crucial in
      posterior axis elongation and in neural tube closure. We found that Cdx2
      expression is also repressed in the dorsal PNPs of Pax3-null embryos. However,
      the ectopically activated Pax3 in the beta-catenin mutants cannot restore Cdx2
      mRNA in the dorsal PNP, suggesting that the presence of both beta-catenin and
      Pax3 is required for regional Cdx2 expression. Thus, beta-catenin signaling is
      required for caudal neural tube closure and elongation, acting through the
      transcriptional regulation of key target genes in the PNP.

PMID- 24284206
TI  - A bi-modal function of Wnt signalling directs an FGF activity gradient to
      spatially regulate neuronal differentiation in the midbrain.
AB  - FGFs and Wnts are important morphogens during midbrain development, but their
      importance and potential interactions during neurogenesis are poorly understood.
      We have employed a combination of genetic and pharmacological manipulations in
      zebrafish to show that during neurogenesis FGF activity occurs as a gradient
      along the anterior-posterior axis of the dorsal midbrain and directs spatially
      dynamic expression of the Hairy gene her5. As FGF activity diminishes during
      development, Her5 is lost and differentiation of neuronal progenitors occurs in
      an anterior-posterior manner. We generated mathematical models to explain how Wnt
      and FGFs direct the spatial differentiation of neurons in the midbrain through
      Wnt regulation of FGF signalling. These models suggested that a negative-feedback
      loop controlled by Wnt is crucial for regulating FGF activity. We tested Sprouty
      genes as mediators of this regulatory loop using conditional mouse knockouts and
      pharmacological manipulations in zebrafish. These reveal that Sprouty genes
      direct the positioning of early midbrain neurons and are Wnt responsive in the
      midbrain. We propose a model in which Wnt regulates FGF activity at the isthmus
      by driving both FGF and Sprouty gene expression. This controls a dynamic,
      posteriorly retracting expression of her5 that directs neuronal differentiation
      in a precise spatiotemporal manner in the midbrain.

PMID- 24284208
TI  - Adaptation of the length scale and amplitude of the Bicoid gradient profile to
      achieve robust patterning in abnormally large Drosophila melanogaster embryos.
AB  - The formation of patterns that are proportional to the size of the embryo is an
      intriguing but poorly understood feature of development. Molecular mechanisms
      controlling such proportionality, or scaling, can be probed through quantitative
      interrogations of the properties of morphogen gradients that instruct patterning.
      Recent studies of the Drosophila morphogen gradient Bicoid (Bcd), which is
      required for anterior-posterior (AP) patterning in the early embryo, have
      uncovered two distinct ways of scaling. Whereas between-species scaling is
      achieved by adjusting the exponential shape characteristic of the Bcd gradient
      profile, namely, its length scale or length constant (lambda), within-species
      scaling is achieved through adjusting the profile's amplitude, namely, the Bcd
      concentration at the anterior (B0). Here, we report a case in which Drosophila
      melanogaster embryos exhibit Bcd gradient properties uncharacteristic of their
      size. The embryos under investigation were from a pair of inbred lines that had
      been artificially selected for egg size extremes. We show that B0 in the large
      embryos is uncharacteristically low but lambda is abnormally extended. Although
      the large embryos have more total bcd mRNA than their smaller counterparts, as
      expected, its distribution is unusually broad. We show that the large and small
      embryos develop gene expression patterns exhibiting boundaries that are
      proportional to their respective lengths. Our results suggest that the large-egg
      inbred line has acquired compensating properties that counteract the extreme
      length of the embryos to maintain Bcd gradient properties necessary for robust
      patterning. Our study documents, for the first time to our knowledge, a case of
      within-species Bcd scaling achieved through adjusting the gradient profile's
      exponential shape characteristic, illustrating at a molecular level how a
      developmental system can follow distinct operational paths towards the goal of
      robust and scaled patterning. 

PMID- 24284210
TI  - Retinoic acid controls proper head-to-trunk linkage in zebrafish by regulating an
      anteroposterior somitogenetic rate difference.
AB  - During vertebrate development, the primary body axis elongates towards the
      posterior and is periodically divided into somites, which give rise to the
      vertebrae, skeletal muscles and dermis. Somites form periodically from anterior
      to posterior, and the anterior somites form in a more rapid cycle than the
      posterior somites. However, how this anteroposterior (AP) difference in
      somitogenesis is generated and how it contributes to the vertebrate body plan
      remain unclear. Here, we show that the AP difference in zebrafish somitogenesis
      originates from a variable overlapping segmentation period between one somite and
      the next. The AP difference is attributable to spatiotemporal inhibition of the
      clock gene her1 via retinoic acid (RA) regulation of the transcriptional
      repressor ripply1. RA depletion thus disrupts timely somite formation at the
      transition, eventually leading to the loss of one somite and the resultant
      cervical vertebra. Overall, our results indicate that RA regulation of the AP
      difference is crucial for proper linkage between the head and trunk in the
      vertebrate body plan. 

PMID- 24284209
TI  - Function of the Drosophila receptor guanylyl cyclase Gyc76C in PlexA-mediated
      motor axon guidance.
AB  - The second messengers cAMP and cGMP modulate attraction and repulsion mediated by
      neuronal guidance cues. We find that the Drosophila receptor guanylyl cyclase
      Gyc76C genetically interacts with Semaphorin 1a (Sema-1a) and physically
      associates with the Sema-1a receptor plexin A (PlexA). PlexA regulates Gyc76C
      catalytic activity in vitro, and each distinct Gyc76C protein domain is crucial
      for regulating Gyc76C activity in vitro and motor axon guidance in vivo. The
      cytosolic protein dGIPC interacts with Gyc76C and facilitates Sema-1a
      PlexA/Gyc76C-mediated motor axon guidance. These findings provide an in vivo link
      between semaphorin-mediated repulsive axon guidance and alteration of
      intracellular neuronal cGMP levels.

PMID- 24284211
TI  - GABA suppresses neurogenesis in the adult hippocampus through GABAB receptors.
AB  - Adult neurogenesis is tightly regulated through the interaction of neural
      stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA
      activation of GABAA receptor ion channels, are important niche signals. We show
      that adult mouse hippocampal NSCs and their progeny express metabotropic GABAB
      receptors. Pharmacological inhibition of GABAB receptors stimulated NSC
      proliferation and genetic deletion of GABAB1 receptor subunits increased NSC
      proliferation and differentiation of neuroblasts in vivo. Cell-specific
      conditional deletion of GABAB receptors supports a cell-autonomous role in newly
      generated cells. Our data indicate that signaling through GABAB receptors is an
      inhibitor of adult neurogenesis. 

PMID- 24284207
TI  - Induction of endocycles represses apoptosis independently of differentiation and
      predisposes cells to genome instability.
AB  - The endocycle is a common developmental cell cycle variation wherein cells become
      polyploid through repeated genome duplication without mitosis. We previously
      showed that Drosophila endocycling cells repress the apoptotic cell death
      response to genotoxic stress. Here, we investigate whether it is differentiation
      or endocycle remodeling that promotes apoptotic repression. We find that when
      nurse and follicle cells switch into endocycles during oogenesis they repress the
      apoptotic response to DNA damage caused by ionizing radiation, and that this
      repression has been conserved in the genus Drosophila over 40 million years of
      evolution. Follicle cells defective for Notch signaling failed to switch into
      endocycles or differentiate and remained apoptotic competent. However, genetic
      ablation of mitosis by knockdown of Cyclin A or overexpression of fzr/Cdh1
      induced follicle cell endocycles and repressed apoptosis independently of Notch
      signaling and differentiation. Cells recovering from these induced endocycles
      regained apoptotic competence, showing that repression is reversible. Recovery
      from fzr/Cdh1 overexpression also resulted in an error-prone mitosis with
      amplified centrosomes and high levels of chromosome loss and fragmentation. Our
      results reveal an unanticipated link between endocycles and the repression of
      apoptosis, with broader implications for how endocycles may contribute to genome
      instability and oncogenesis.

PMID- 24284212
TI  - FOXD1 promotes nephron progenitor differentiation by repressing decorin in the
      embryonic kidney.
AB  - Forkhead transcription factors are essential for diverse processes in early
      embryonic development and organogenesis. Foxd1 is required during kidney
      development and its inactivation results in failure of nephron progenitor cell
      differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron
      progenitor cells, suggesting an essential role for the progenitor cell niche in
      nephrogenesis. To better understand how cortical interstitial cells in general,
      and FOXD1 in particular, influence the progenitor cell niche, we examined the
      differentiation states of two progenitor cell subtypes in Foxd1(-/-) tissue. We
      found that although nephron progenitor cells are retained in a primitive CITED1
      expressing compartment, cortical interstitial cells prematurely differentiate. To
      identify pathways regulated by FOXD1, we screened for target genes by comparison
      of Foxd1 null and wild-type tissues. We found that the gene encoding the small
      leucine-rich proteoglycan decorin (DCN) is repressed by FOXD1 in cortical
      interstitial cells, and we show that compound genetic inactivation of Dcn
      partially rescues the failure of progenitor cell differentiation in the Foxd1
      null. We demonstrate that DCN antagonizes BMP/SMAD signaling, which is required
      for the transition of CITED1-expressing nephron progenitor cells to a state that
      is primed for WNT-induced epithelial differentiation. On the basis of these
      studies, we propose a mechanism for progenitor cell retention in the Foxd1 null
      in which misexpressed DCN produced by prematurely differentiated interstitial
      cells accumulates in the extracellular matrix, inhibiting BMP7-mediated
      transition of nephron progenitor cells to a compartment in which they can respond
      to epithelial induction signals. 

PMID- 24284213
TI  - Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of
      prospective studies.
AB  - BACKGROUND: Though vitamin C supplementation has shown no observed effects on
      stroke prevention in several clinical trials, uncertainty remains as to whether
      long-term, low-dose intake influences the development of stroke among general
      populations. Furthermore, the association between circulating vitamin C and the
      risk of stroke is also unclear. For further clarification of these issues, we
      conducted a meta-analysis of prospective studies. METHODS AND RESULTS: PubMed and
      EMBASE databases were searched, and the bibliographies of the retrieved articles
      were also reviewed to identify eligible studies. Summary relative risk (RRs) with
      corresponding 95% confidence intervals (CIs) were computed with a random-effects
      model. The summary RR for the high-versus-low categories was 0.81 (95% CI: 0.74
      to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to
      0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day
      increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and
      for each 20 MUmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to
      0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for
      high-versus-low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies). CONCLUSIONS: This
      meta-analysis suggests significant inverse relationships between dietary vitamin
      C intake, circulating vitamin C, and risk of stroke.

PMID- 24284214
TI  - Safety of percutaneous patent ductus arteriosus closure: an unselected
      multicenter population experience.
AB  - BACKGROUND: The technique and safety of transcatheter patent ductus arteriosus
      (PDA) closure have evolved during the past 20 years. We sought to report a
      multicenter experience of PDA closure with a focus on the rate of adverse events
      (AE) and a review of institutional practice differences. METHODS AND RESULTS:
      Outcome data on transcatheter PDA closure were collected at 8 centers
      prospectively using a multicenter registry (Congenital Cardiac Catheterization
      Project on Outcome Registry). Between February 2007 and June 2010, 496 PDA
      closures were recorded using a device in 338 (68%) or coils in 158 (32%). Most
      patients had an isolated PDA (90%). Fifty percent of patients were between 6
      months and 3 years old, with only 40 patients (8%) <6 months old. Median minimum
      PDA diameter was 2.5 mm (range 1 to 12 mm; IQR 2 to 3 mm) for device closure and
      1 mm (range 0.5 to 6 mm; IQR 1 to 2 mm) for coil closure (P<0.001). A device
      rather than coil was used in patients <3 years, weight <11 kg, and with a PDA
      minimum diameter >2 mm (all P<0.001). Three of 8 centers exclusively used a
      device for PDAs with a diameter >1.5 mm. In 9% of cases (n=46), an AE occurred;
      however, only 11 (2%) were classified as high severity. Younger age was
      associated with a higher AE rate. Coil-related AEs were more common than device
      related AEs (10% versus 2%, P<0.001). CONCLUSIONS: PDA closure in the present era
      has a very low rate of complications, although these are higher in younger
      children. Technical intervention-related events were more common in coil
      procedures compared with device procedures. For PDAs <=2.5 mm in diameter,
      institutional differences in preference for device versus coil exist.

PMID- 24284215
TI  - [Analysis of normal pelvis morphometry of modern Chinese southern Han female and
      its correlation with age].
AB  - OBJECTIVE: To analyze the normal pelvis morphometry of Chinese southern Han
      female and its correlation with age. METHODS: From August 2009 to September 2011,
      289 Han nationality females who received pelvis CT scan at Nanfang Hospital of
      Southern Medical University were eligible for the study. Their mean age was 43.5
      years, with normal body development and no pelvic abnormality. The patients were
      divided into 3 age groups: 25 to 40 (n = 109), 41 to 50 (n = 115), and >50 years
      (n = 65). After constructing a three-dimensional digital model of the pelvis, the
      following parameters were measured, including transverse inlet diameter,
      posterior sagittal diameter of pelvic inlet, sagittal inlet, diagonal conjugate,
      biischial diameter, posterior sagittal diameter of midpelvis, sagittal midpelvic
      diameter, intertuberous distance, posterior sagittal diameter of outlet, angle of
      pubic arch, sagittal outlet, penal height, sacrum length and sacrum curvature.
      The relationship between all parameters and age was analyzed. RESULTS: (1) The
      posterior sagittal diameters of pelvic inlet of the 25 to 40 age group, 41 to 50
      age group, >50 years age group were (53 +/- 8), (51 +/- 7), (48 +/- 6) mm. The
      sagittal inlet of the three groups were (122 +/- 8), (120 +/- 9), (114 +/- 8) mm.
      And the diagonal conjugate of the three groups were (135 +/- 10), (132 +/- 9),
      (127 +/- 9) mm. All had significant differences among the three groups (P < 0.01)
      . (2) The posterior sagittal diameter of midpelvis of the three groups were (43
      +/- 6), (44 +/- 6), (43 +/- 7) mm, and the sagittal midpelvic diameter of the
      three groups were (119 +/- 8), (120 +/- 8), (119 +/- 7) mm, with no significant
      difference among the three groups (P > 0.05). (3) The intertuberous distance of
      the three groups were (122 +/- 11), (121 +/- 10), (117 +/- 11) mm, and the
      posterior sagittal diameter of outlet of the three groups were (56 +/- 9), (58 +/
      8), (57 +/- 9) mm. There was no significant difference among the three groups (P
      > 0.05) .(4) Penal height of three groups were (31 +/- 3), (33 +/- 3), (34 +/- 3)
      mm, there was with significant differences (P < 0.01) .(5) Pearson correlation
      analysis showed that penal height was positively correlated with age (r = 0.331,
      P < 0.05), while sagittal inlet, posterior sagittal diameter of inlet, diagonal
      conjugate, intertuberous distance, angle of pubic arch, sacrum length and sacrum
      curvature were negatively correlated with age (r = -0.120 to -0.343, P < 0.05).
      CONCLUSIONS: The shape of the pelvic inlet of Chinese southern Han female changed
      from sagittal elliptic into transverse elliptic form, and the posterior part of
      pelvic inlet became larger.Sacral concavity was increased and the pelvis became
      deeper. Mid pelvis and the pelvic outlet was almost unchanged, and showed no
      correlation with age.

PMID- 24284216
TI  - [Analysis of clinical features of pregnant women with hypertrophic
      cardiomyopathy].
AB  - OBJECTIVE: To discuss the clinical features of pregnant women with hypertrophic
      cardiomyopathy (HCM). METHODS: There were 28 patients with HCM who delivered in
      Renji hospital of Shanghai Jiaotong University from January 2000 to August 2012.
      Clinical data were analyzed, including diagnosis, cardiac functional grading,
      gestational weeks of delivery, delivery mode, birth weight, Apgar scores, etc.
      RESULTS: (1) Of all the 28 patients, 14 (50%) were diagnosed before pregnancy and
      others (50%) were diagnosed during pregnancy.(2) Four cases were obstructive HCM
      (14%), 3 with cardiac function grade I and 1 with grade II. Twenty four cases
      were non-obstructive HCM (86%), 14 with cardiac function grade I, 9 with grade II
      and 1 with grade IV. (3) Of all the 28 patients, 4 had family history, 18 (64%)
      had clinical symptoms or signs which occurred in 8-32 gestational weeks. Twenty
      three cases had abnormal ECG (82%). Among them 21 had non-obstructive HCM (88%),
      with average interventricular septal thickness of (22 +/- 3) mm. The other 2
      patients had obstructive HCM, with average interventricular septal thickness of
      (23 +/- 4) mm.7 patients (7/28, 25%) had mild-to-moderate pulmonary hypertension
      [6 with non-obstructive HCM (6/24, 25%) ], and 10 patients had abnormal
      myocardial enzyme spectrum or troponin levels [9 with non-obstructive HCM (9/24,
      38%) ].(4) Among all the patients, only one had vaginal delivery and others
      received cesarean section. Twenty-two patients had term pregnancies and 6 had
      preterm birth. The average gestational weeks of delivery in non-obstructive HCM
      and obstructive HCM were (36.5 +/- 2.5) and (38.5 +/- 0.4) weeks, respectively.
      The average birth weight of neonates were (2684 +/- 563) and (3164 +/- 321) g,
      and Apgar scores were 9.9 and 10 (10 minutes) respectively. Patients transferred
      to NICU after delivery were 8 and 0. There was 1 maternal death (with non
      obstructive HCM whose ejection fraction was only 26%) and no perinatal death.
      CONCLUSIONS: More attention should be paid to the clinical signs and abnormal
      ECG.HCM could be definitely diagnosed by timely echocardiography. Patients with
      hypertrophic cardiomyopathy were mainly non-obstructive HCM, with cardiac
      function grade I and II. Monitoring the change of ejection fraction during
      pregnancy would help. Perinatal outcomes were fine.

PMID- 24284217
TI  - [Relationship between pigment epithelium-derived factor expressed in placentas
      and the pathogenesis of preeclampsia disease].
AB  - OBJECTIVE: To investigate the effect of pigment epithelium-derived factor (PEDF)
      on the pathogenesis of preeclampsia disease, by detecting the expression of PEDF
      in the placentas, as well as the relationship between PEDF and the production of
      placental vessels. METHODS: A study was performed in 60 cases of pregnant women
      with preeclampsia in the obstetrical department of Nanfang Hospital affiliated to
      southern medical university from October 2011 to January 2013, in which 30 cases
      were patients with mild preeclampsia(mPE) and other 30 cases were those with
      severe preeclampsia (sPE).40 normal pregnant women who also been hospitalized and
      delivered were selected as control group. The expression of PEDF and micro-vessel
      density (MVD) in placentas were assayed by using western blot and SP
      immunohistochemical method, then the relationship between PEDF and MVD was
      analyzed. RESULTS: (1) The pathological changes of placentas:the placental weight
      were lightened obviously in the mild preeclampsia and severe preeclampsia groups,
      the reduced blood vessels and luminal stegnosis were found in chorionic villus,
      basement membrane of trophocytes were thickening. The hyperplasia
      syneytiotrophoblast were like nodosity, with focus infarction, fibrinoid
      necrosis, or thrombogenesis.While there was no the above mentioned pathological
      alteration in normal control group. (2)The levels of PEDF expression in mild and
      severe preeclampsia group were 0.63 +/- 0.09, 0.93 +/- 0.07, while 0.47 +/- 0.04
      in control group, which in mild and sever preeclampsia groups were significantly
      higher than that in normal group (P < 0.05). Compared to mild preeclampsia group,
      the expression of PEDF was significantly increased in severe preeclampsia group,
      there was statistical significance between the difference (P < 0.05).(3) The
      amount of microvessel density (MVD) in mild and severe preeclampsia group were
      106 +/- 9, 93 +/- 8, while 136 +/- 9 in control group, which were significantly
      reduced in mild and severe preeclampsia group, compared to that in normal control
      group (P < 0.05). And it was significantly lower in severe preeclampsia group
      than that in mild preeclampsia group (P < 0.05). (4) The expression of PEDF was
      negatively correlated with the amount of MVD in mild and severe preeclampsia
      group (r = -0.426, P < 0.05; and r = -0.646, P < 0.05 respectively), which was
      also negative in control group (r = -0.589, P < 0.05). CONCLUSION: Increased PEDF
      expression in placentas of women with preeclampsia induce the dysfunction of the
      placental vascular reconstruction and the pathological alteration like ischemic
      and hypoxia in placentas, which may be involved in pathogenesis and pathogenic
      progress of preeclampsia.

PMID- 24284218
TI  - [Study on concomitant surgical correction of pelvic organ prolapse and TVT-O for
      treatment of stress urinary incontinence].
AB  - OBJECTIVE: To investigate the necessity, safety and efficacy of transobturator
      tension-free vaginal tape (TVT-O) for treatment of stress urinary incontinence
      (SUI) during transvaginal corrective operation of pelvic organ prolapse (POP).
      METHODS: From Jan. 2005 to Dec. 2010, 92 patients undergoing transvaginal pelvic
      reconstruction surgery for correction of POP concomitant TVT-O for treatment of
      SUI in Department of Obstetrics and Gynecology affiliated to Beijing Chaoyang
      Hospital as concomitant surgery group were enrolled in this retrospective study
      matched with 90 patients with mild SUI without SUI surgery as non-concomitant
      surgery group and 120 patients without SUI as control group.Variable clinical
      index, clinical efficacy and complications were compared among those three
      groups. RESULTS: Compared with those in the other two groups, the mean age [(62
      +/- 11) years] was lower (P = 0.007,0.038), the operation time only slightly
      increased (12.8 min and 12.9 min respectively) significantly in concomitant TVT-O
      group. The bleeding loss and the length of staying hospital after operation all
      exhibited no significant differences within three groups (P > 0.05). The
      effective rate for SUI was 96.7% (89/92) in concomitant TVT-O group, corrective
      operation of POP was ineffective for 74.4% (67/90) SUI, 9.2% (11/120) patients
      presented new SUI in the patients without SUI preoperatively. CONCLUSIONS: TVT-O
      is a simple, safe and effective method in the treatment of SUI, which is more
      suitable for performing simultaneously during the corrective operation of
      POP.Efficacy of SUI correction was limited in those patients undergoing only
      pelvic reconstructive surgery. However, a preventive anti-incontinence procedure
      is not recommended because of the lower incidence in POP patients without SUI
      preoperatively.

PMID- 24284219
TI  - [Clinical value of three-dimensional transvaginal sonography in diagnosis of
      septate uterus and prediction of adverse pregnancy outcome].
AB  - OBJECTIVE: To investigate clinical value of three-dimensional transvaginal
      sonography (3D-TVS) in the diagnosis of septate uterus and the relationship
      between its parameters and adverse pregnancy. METHODS: From Mar. 2010 to Sept.
      2011, 73 patients (aged 23-35 years) with septate uterus who were diagnosed by 3D
      TVS in Fujian Province Maternal and Child Health Hospital were enrolled in this
      retrospective study. The septum width, septum angle, septum length and the length
      of remaining uterine cavity were measured among the patients with subseptate
      uterus, and then, the distortion rate was calculated. The hysteroscopic surgery
      was used as the gold standard, and the diagnostic titer of 3D-TVS in the
      diagnosis of septate uterus was determined.Receiver operating characteristic
      curve (ROC) were plotted to evaluate the diagnostic titer of uterine parameters
      measured by 3D-TVS in predicting the adverse pregnancy outcome among patients
      with subseptate uterus.Univariate logistic regression was used to analyze the
      effectiveness of uterine parameters on adverse pregnancy outcome. RESULTS: Using
      hysteroscopic surgery as the gold standard, the coincidence rate of diagnosis of
      septate uterus by 3D-TVS was 94% (69/73) . Among the patients with septate
      uterus, 25% (17/69) were complete septate uterus, 75% (52/69) were subseptate
      uterus. Among patients with subseptate uterus, the septum length[(2.2 +/- 0.6)
      cm] and distortion rate in patients with adverse pregnancy (0.60 +/- 0.10) were
      significantly higher than those without adverse pregnancy [(1.5 +/- 0.6) cm,0.43
      +/- 0.13, both P < 0.05]. However, no significant difference in the width, angle
      and length of septum were observed between the two groups (P > 0.05). The area
      under ROC curve (AUC) of septum length and distortion rate in determining adverse
      pregnancy were 0.833 (95%CI: 0.721-0.944) and 0.800 (95%CI: 0.671-0.929),
      respectively. The optimal cutoff point of septum length was 1.94 cm, with the
      sensitivity was 74.3% and the specificity was 76.5%; the optimal cutoff point of
      distortion rate was 0.48, with the sensitivity was 77.1% and the specificity was
      76.5%. The expectation morbidity ratio of adverse pregnancy was 2.717, 3.067 and
      0.514 by every adding level of septum length, distortion rate, and length of
      remaining uterine cavity, respectively. CONCLUSIONS: 3D-TVS showed high accuracy
      in diagnosis of septate uterus. The septum length and distortion rate may predict
      the risk of adverse pregnancy, and the value of them can be used for screening
      adverse pregnancy in clinical practice.

PMID- 24284220
TI  - [Expression of nitric oxide in uterine junctional zone of patients with
      adenomyosis].
AB  - OBJECTIVE: To investigate the relationship between nitric oxide and contractile
      disfunction of junctional zone of smooth muscle by detecting the expression of
      nitric oxide in uterine junctional zone in patients with adenomyosis. METHODS:
      From February 2012 to July 2012, 23 patients with adenomyosis undergoing
      hysterectomy as adenomyosis group matched as 16 patients with cervical carcinoma
      or ovarian cancer were enrolled as control group in Center of Minimally Invasive
      Gynecology, Beijing Obstetrics and Gynecology Hospital.Location of nitric oxide
      synthase (inducible NOS and endothelial NOS) in uterine junctional zone was
      analyzed by immunohistochemistry.Smooth muscle cells of junctional zone were
      cultured and cellular mRNA levels of nitric oxide synthase were detected by real
      time polymerase chain reaction.Furthermore, concentration of nitrites in lysates
      of fresh junctional zone tissues and cultured cells were determined by Griess
      reaction. RESULTS: (1) The expression of nitric oxide synthase proteins in smooth
      muscle cells of junctional zone tissues:the staining of iNOS was intensive in
      smooth muscle cells of junctional zone in patients with adenomyosis, while
      staining of eNOS was scant. Both staining of iNOS and eNOS were not observed in
      control group.(2) The expression of NOS genes in cultured smooth muscle cells
      from adenomyosis:mRNA level of iNOS was elevated by 1.5 times (P < 0.01) while
      eNOS level was reduced by 2.6 times when compared with those in control groups (P
      < 0.05) .(3) Nitrites concentration in lysates of junctional zone tissues and
      cultured cells:concentrations of nitrites in lysates of 100 mg tissues were
      respectively (37 +/- 8) umol/L and (28 +/- 5) umol/L in adenomyosis and control
      group (P > 0.05).While concentrations of nitrites in 1*10(6) cells were
      respectively (11.8 +/- 0.6) umol/L and (10.8 +/- 1.5) umol/L in adenomyosis and
      control group, which did not reach statistical difference (P > 0.05). CONCLUSION:
      Up-regulation of nitric oxide might be associated with contractile disfunction of
      smooth muscle cells in uterine junctional zone of patients with adenomyosis.

PMID- 24284221
TI  - [Short-term outcome of leuprorelin acetate in preventing recurrence of ovarian
      endometrioma after conservative surgery].
AB  - OBJECTIVE: To evaluate the short-term effect of leuprorelin acetate microspheres
      in preventing recurrence of ovarian endometrioma after conservative surgery.
      METHODS: From January 2011 to September 2011, 190 ovarian endometrioma patients
      undergoing conservative laparoscopic surgery at Affiliated Obstetrics and
      Gynecology Hospital Affiliated to Fudan University were enrolled in this
      retrospective study. Among 184 patients were followed up, the range of following
      up were 12 to 21 months. 116 cases presented dysmenorrheal. Based on
      postoperative treatment, they were classified into 124 cases treated by domestic
      gonadotropin releasing hormone agonist(GnRH-a) post-operatively for 3-6 months
      and 60 cases without postoperative treatment. Among all, 63 patients were treated
      with, that was leuprorelin acetate microspheres for injection (Beiyi, 3.75 mg,
      q28 d), 61 patients were treated with imported GnRH-a post-operatively for 3-6
      months, that were either Zoladex(3.6 mg, q28 d), Dophereline(3.75 mg, q28 d) or
      Enatone (3.75 mg, q28 d). The recurrence and pain improvement were compared among
      those groups. RESULTS: (1) The total rate of cyst recurrence was 12.5% (23/184)
      while the average recurrent time was (13.7 +/- 2.6) months (2-21 months). The
      cyst recurrence rate was significantly lower in patients treated with GnRH-a post
      operatively than those who didn't take medications [21.7% (13/60) versus 8.1%
      (10/24), P < 0.05]. However, there was no significant difference between domestic
      GnRH-a group and the imported one [7.9% (5/63) versus 8.2% (5/61), P > 0.05]. (2)
      After conservative surgery, symptoms were found to be relieved in 87.1% (101/116)
      patients among 116 patients complaining of dysmenorrheal pre-operatively and the
      pain recurrence rate was 12.9% (13/101). However, there was no significant
      difference in either symptom relief rate or pain recurrence rate among different
      groups. The symptom relief rate were 87% (33/38), 86% (37/43) and 89% (31/35)
      while the pain recurrence rate were 12% (4/33), 14% (5/37) and 13% (4/31)
      respectively in none, imported GnRH-a group and domestic GnRH-a group.
      CONCLUSIONS: Leuprorelin acetate microspheres could be effective in preventing
      recurrence of ovarian endometrioma, but not in symptom relieving after
      conservative surgery in short term. The effect of domestic and imported GnRH-a
      was similar.

PMID- 24284222
TI  - [Study on gasless-laparoscopic vaginoplasty using sigmoid colon segment].
AB  - OBJECTIVE: To study the clinical effect of gasless-laparoscopic vaginoplasty
      using sigmoid colon segment. METHODS: Clinical data of 119 cases undergoing
      laparoscopic or gasless-laparoscopic vaginoplasty using a vascularized pedicled
      sigmoid colon segment in Beijing Anzhen Hospital from January 2007 to December
      2010 were reviewed retrospectively. Those patients were classified into 57 cases
      with laparoscopic sigmoid colon vaginoplasty and 62 cases with gasless
      laparoscopic sigmoid colon vaginoplasty. The operation time, blood loss in
      operating, bowel movement after operation, postoperation hospital duration, side
      effect, and artificial vagina were compared between laparoscopic and gasless
      laparoscopic group. RESULTS: The vaginoplasty were preformed successfully in 119
      cases. The mean operation time of were (159 +/- 18) min in laparoscopic group and
      (146 +/- 17) min in gasless-laparoscopic group, respectively, which reached
      statistical difference (P < 0.01). The blood loss in operating were (83 +/- 14)
      ml and (86 +/- 13) ml, bowel movement after operation were (68 +/- 8) hours and
      (68 +/- 11) hours, and postoperation hospital duration were (11.1 +/- 1.3) days
      and (11.4 +/- 1.9) days respectively in laparoscopic group and gasless
      laparoscopic group. No significant difference were found in the blood loss in
      operating, bowel movement after operation, and postoperation hospital duration
      between two groups (P > 0.05) .No intraoperative complication occurred. There
      were two cases with incomplete adhesive intestinal obstruction at 15-20 days
      postoperatively, which one was in laparoscopic group and one was in gas-less
      laparoscopic group. At 6-50 months of following up (median time 12 months), all
      artificial vaginas had a capacity of over two fingers in wideness and 12-15 cm in
      length. Vaginal discharges resembled a milky white water or mucus without odour.
      Eighty-five patients with sexual intercourse reported satisfactory feeling. One
      patients complained vaginal stenosis in laparoscopic group. CONCLUSION: Gasless
      laparoscopic vaginoplasty using sigmoid colon segment is an alternative feasible
      and practical treatment.

PMID- 24284223
TI  - [Application of gene array chip in diagnosis of cytogenetics of recurrent
      spontaneous abortion].
AB  - OBJECTIVE: To investigate clinical value of single nucleotide polymorphism array
      (SNP-array) gene chip technique in diagnosis of genetics of recurrent spontaneous
      abortion(RSA). METHODS: From January to October 2012, the 26 patients with more
      than twice of spontaneous abortion in Huzhou Maternal and Child Health Care
      Hospital were enrolled in this study(RSA group). Meanwhile 20 cases with induced
      abortion were taken as control group. All aborted tissues were analyzed with
      conventional cytogenetic karyotyping and SNP-array, respectively. RESULTS:
      Chorionic villus chromosomal examination was successfully done in 19 cases (73%,
      19/26) , which 10 cases were found with chromosomal anomaly, the overall
      detection rate is 10/19. However, SNP-array analysis was successfully performed
      in all 26 cases. The overall rate of detection was 100%, and abnormalities were
      found in 15 cases, which reached the detection rate was 58% (15/26). Chorionic
      villus chromosomal examination was successfully done in 16 cases (16/20) in
      control group, and none of the resluts was chomosomal anomaly; SNP-array analysis
      was successfully performed in all 20 cases (20/20), and none was found
      abnormalities. CONCLUSION: SNP-array gene chip technique showed highly accurate
      feature, which could be used in cytogenetic diagnosis of recurrent spontaneous
      abortion.

PMID- 24284224
TI  - [Pregnant rate and pregnancy-relating factors of patients with early endometrial
      carcinoma and severe atypical hyperplasia of endometrium after fertility
      preserving treatment by progestin].
AB  - OBJECTIVE: To summarize the pregnant rate of patients with early endometrial
      carcinoma and severe atypical hyperplasia after fertility-preserving treatment
      and analyze their pregnancy-relating factors. METHODS: Endometrial curettage was
      used to evaluate the therapy response of endometrium after every 3 months of
      administration of high-dose progestin as fertility-sparing treatment for 51
      patients with stage I endometrial carcinoma or severe endometrial atypical
      hyperplasia from Jun. 1996 to Jan. 2010. Individualized maintained treatment was
      given to patients after achieving complete remission of the endometrium. Pregnant
      results and pregnancy-relating factors were analyzed retrospectively. RESULTS:
      The median age of all the 51 patients was 29 years old. Forty-five (88%, 45/51)
      achieved complete response. Of the 34 cases who desired to conceive after
      complete response, 16 of them had 22 pregnancies, the pregnant rate was 47%
      (16/34); and 12 women obtained healthy live birth baby, the fertility rate was
      35% (12/34). The pregnant rate of patients at age >35 or <= 35 was 0/2 and 50%
      (16/32) respectively (P > 0.05). The pregnant rate of patients with or without
      infertility was 40% (8/20) and 8/14, with endometrial cancer or severe atypical
      hyperplasia was 40% (10/25) and 6/9, respectively (all P > 0.05). The pregnant
      rate of patients who received in vitro fertilization-embryo transfer, ovulation
      promotion, or no treatment was 7/7, 6/16 and 3/11 respectively (P < 0.01).
      CONCLUSIONS: Fertility-preserving treatment for early endometrial cancer and
      severe atypical hyperplasia with high-dose progestin could achieve higher
      response rate. Assisted reproductive technologies could significantly increase
      the chance of conception.

PMID- 24284225
TI  - [Preliminary observation on antitumor effect of HPV58 composite DNA vaccine].
AB  - OBJECTIVE: To initially observe the antitumor immune of PVAX1-HPV58mE6E7FcGB
      composite DNA vaccine. METHODS: Before detecting immune effect of the vaccine,
      the B16-HPV58E6E7 tumor cell line was built which could steadily express
      HPV58E6E7 fusion gene. Then, HPV58E6E7-GST fusion protein as an antigen was
      expressed and purified. Before or after immunized with the vaccine, the C57BL/6
      mice were challenged by B16-HPV58E6E7 cells. Anti-tumor transplantation and tumor
      growth inhibition experiment were performed to observe prevention and treatment
      effects on the vaccine. Specific humoral and cellular immune responses in the
      immunized mice were detected by ELISA, enzyme linked immunospot assay (ELISPOT)
      and cytotoxic T lymphocyte (CTL) method. RESULTS: In the anti-tumor
      transplantation experiment, tumor formation rate was only 9/15 in the mice which
      were immunized by PVAX1-HPV58mE6E7FcGB vaccine, time before tumor formation was
      the longest [(13.6 +/- 1.7) days] and tumor growth was the slowest in the vaccine
      group. In tumor growth inhibition experiment, inhibition rate reached 81.4% in
      the vaccine group. Except tumor formation rate, all data in the vaccine group was
      superior to the pure antigen PVAX1-HPV58mE6E7Fc group (P < 0.05). Humoral immune
      effect showed that both the vaccine and the pure antigen could induce specific
      antibody in the immunized mice, and the highest titer were 1: 25 600 and 1: 12
      800, respectively. Although there was not significant difference of antibody
      titer between the vaccine and the pure antigen group (P > 0.05), the number of
      activated T cells in the vaccine group was almost four times as that in the pure
      antigen group [(219 +/- 34)/4*10(5) spleen lymphocytes versus (55 +/- 25)/4*10(5)
      spleen lymphocytes, P < 0.05], and the highest specific CTL that vaccine induced
      was significantly higher than that of pure antigen (43.3% versus 31.3%, P <
      0.05). CONCLUSIONS: Humoral and cellular immune response could be effectively
      stimulated by PVAX1-HPV58mE6E7FcGB composite DNA vaccine. Growth of B16-HPV58E6E7
      cells was significantly inhibited in the immunized mice. The cellular immune
      effect on the vaccine was superior to the pure antigen. Therefore, PVAX1
      HPV58mE6E7FcGB could be used as a candidate vaccine for immune therapy to the
      HPV58 positive tumors and precancerous lesions.

PMID- 24284226
TI  - [Study of growth, invasion and metastasis on ovarian epithelial cancer cell line
      with CCL18 over-expression by mediated in vitro].
AB  - OBJECTIVE: To investigate the effect of growth, invasion and metastasis on
      ovarian cancer cell line SKOV3 with chemokine (C-C motif) ligand 18 (CCL18) over
      expression by mediated in vitro. METHODS: The restructuring plasmid of CCL18
      expression was constructed and SKOV3 cells was transfected with plasmid DNA in
      vitro. The growth curve, cell cycle, cell migration, invasion and adhesion
      capacity in SKOV3-CCL18 cells and control cells were detected by methyl thiazolyl
      tetrazolium (MTT) assay, flow cytometry, transwell chamber, migration invasion
      and fibronectin adhesion method, respectively. RESULTS: (1) CCL18-pEGFP-N1
      plasmid was successfully constructed and transmitted to the SKOV3 cells, the
      stable growth of the subculture SKOV3-CCL18 cells was screening and completed.
      (2) Compared with SKOV3-CCL18 cells and SKOV3 or SKOV3-pEGFP-N1 cells, there was
      not differences statistically significant in growth curve (all P > 0.05); but the
      rate of the SKOV3-CCL18 cells in a proliferative field (S+G2+M) was significantly
      higher than that in SKOV3 or SKOV3-pEGFP-N1 cells (32.80% versus 27.06%, 32.80%
      versus 26.98%, respectively; all P < 0.05). (3) The invasion, migration and
      adhesion capacity of SKOV3-CCL18 cells (being 0.49 +/- 0.18, 1.16 +/- 0.25 and
      0.39 +/- 0.10, respectively) in vitro were significantly higher than those in
      SKOV3 (being 0.23 +/- 0.13, 0.36 +/- 0.10 and 0.16 +/- 0.03, respectively) or
      SKOV3-pEGFP-N1 cells (being 0.19 +/- 0.05, 0.38 +/- 0.23 and 0.13 +/- 0.11,
      respectively; all P < 0.05). CONCLUSION: The CCL18 over-expression in epithelial
      ovarian cancer SKOV3 cells could lead to strengthen ability of invasion,
      migration and adhesion in vitro.

PMID- 24284227
TI  - [Effect on invasion ability of cervical cancer cells after silence heparanase
      gene expression in Hela cells].
AB  - OBJECTIVE: Design and synthesize short hairpin RNA (shRNA) expression vector of
      RNA for specific silencing of heparanase (HPA) gene, screened plasmid which
      silence effects is the best. Observe the function of cell invasion after
      inhibiting the expression of HPA in cervical carcinoma cell lines (HeLa).
      METHODS: The genomic sequence of HPA gene was retrieved from GenBank database.
      Designed four pairs of specific oligonucleotide sequences and a negative control
      according to the shRNA design principles. They were inserted into the vector pYr
      1.1, vectors, and transfected into HeLa cells via lipofectamine. Reverse
      transcription(RT)-PCR and immunofluorescence were employed to detect the
      expression of HPA gene in the transfected cells at the mRNA and protein levels,
      respectively. The plasmid were screened and transfected into HeLa cells, then
      transwell small room stromal invasion experiment were employed to observe the
      cervical carcinoma cell invasion. RESULTS: RT-PCR results of transfected HeLa
      cells shown that the mRNA amplification multiples were 0.54 +/- 0.05 in the HPA
      592 group, 0.89 +/- 0.18 in HPA-995 group, 0.82 +/- 0.22 in the HPA-1351 group,
      0.91 +/- 0.47 in HPA-1658 group. While, they were 1.31 +/- 0.72 and 1.09 +/- 0.16
      in negative control and blank control group, respectively. Green fluorescence was
      visible in the cytoplasm, which indicated that the HPA protein was expressed in
      the cytoplasm, of them the weakest green fluorescence in the HPA-592 group . The
      relative numbers of invasive cells among the HeLa cells were as follows: 182 +/-
      6 in the blank control group, 258 +/- 17 in the negative control group, and 44 +/
      4 in the HPA-592-specific interference group (P < 0.01) . CONCLUSION:
      Successfully screened shRNA vector targeting human HPA, efficiently inhibit
      expression of HPA gene when transfected into HeLa cells, and significantly
      reduced the invasion capacity of cervical carcinoma cells.

PMID- 24284228
TI  - Effect of Allium macrostemon on a rat model of depression studied by using plasma
      lipid and acylcarnitine profiles from liquid chromatography/mass spectrometry.
AB  - The present study aimed to investigate the anti-depressive effect of the
      traditional Chinese medicine Allium macrostemon in a rat model of depression
      induced by exposure to chronic immobilization stress. Lipid and acylcarnitine
      metabolism were set into the focus of this study due to their key role in the
      pathogenesis of depression. Plasma lipid profiling was performed by ultra fast
      liquid chromatography/ion trap-time of flight mass spectrometry. Ultra-high
      performance liquid chromatography/triple quadrupole mass spectrometry was used to
      characterize the plasma acylcarnitine profile. Principal component analysis (PCA)
      revealed distinct differences in plasma lipid and acylcarnitine profiles of
      depressed rats from those in the control rats, which were also validated by
      univariate analysis. Several lysophosphatidylcholines (LPC (18:1->:2), LPC
      (20:1), LPC (O-16:2), and LPC (O-18:3)) as well as most medium- and long-chain
      acylcarnitines were elevated, while some phosphatidylcholines (PC (32:1), PC
      (36:4->:5), PC (37:4), PC (38:4->:6), PC (40:6), PC (O-36:4), and PC (O-38:5))
      and triglycerides (TG (58:12), TG (60:12), and TG (62:13->:14)) were decreased in
      the plasma of depressed rats. These changes indicate that depressed rats were
      associated with inflammatory conditions and an incomplete beta-oxidation of fatty
      acids. Most of these dysregulated metabolites were returned to their normal
      levels after treatment with A. macrostemon according to PCA and univariate
      analysis, highlighting the anti-depressive effect of this traditional Chinese
      medicine. These results show that liquid chromatography/mass spectrometry-based
      quantitative metabolic profiling method is a useful tool to investigate the
      metabolic changes in depression and the anti-depressive effect of traditional
      Chinese medicine. 

PMID- 24284229
TI  - HPLC/qTOF-MS-oriented characteristic components data set and chemometric analysis
      for the holistic quality control of complex TCM preparations: Niuhuang Shangqing
      pill as an example.
AB  - The quality control of Da-Fu-Fang (DFF), referring to the traditional Chinese
      medicine (TCM) preparations comprising more than 10 TCMs, is challenging due to
      their extreme chemical complexity. In this study, a strategy is proposed for the
      holistic quality control of DFFs based on HPLC/qTOF-MS-oriented characteristic
      components data set (CCDS) and chemometric analysis. Niuhuang Shangqing pill
      (NHSQP), composed of 19 TCMs, is used to illustrate this strategy. The
      fingerprint profiling of NHSQP by HPLC/qTOF-MS resulted in the characterization
      of 190 compounds, comprising 47 unambiguously identified by reference standard
      comparison. A CCDS containing 60 characteristic components was constructed by
      analyzing the MS spectral differentiation of the crude drugs, a laboratory-made
      NHSQP powder, and negative control preparations. With the established CCDS, it
      was possible to simultaneously monitor 16 out of the 19 drugs involved in NHSQP.
      Subsequently, 26 NHSQP samples from different vendors were evaluated by the
      qualitative and semi-quantitative analyses of their LC/MS fingerprint data. The
      60 characteristic components were detected in all of the NHSQP samples, which
      demonstrated their authenticity. When compared with the standard sample No. 3,
      however, 15 of the NHSQP samples exhibited inferior quality. Samples No. 21 and
      No. 13 differed significantly based on a PCA score plot, and the components
      responsible for the differentiation were confirmed to originate from different
      TCMs. This strategy is a powerful and easy method to implement and provides a
      potential approach to establishing the holistic quality control of complex TCM
      preparations. 

PMID- 24284230
TI  - Surgical anterior ventricular endocardial restoration performed with total
      arterial revascularization: serial 5-year follow-up.
AB  - OBJECTIVE: We evaluated the changes in left ventricular (LV) function and volumes
      after surgical anterior ventricular endocardial restoration. METHODS: A total of
      63 patients who had undergone surgical anterior ventricular endocardial
      restoration and total arterial revascularization were included. Echocardiography
      and myocardial single photon emission computed tomography were performed to
      examine LV function and volumes preoperatively, early postoperatively, and
      annually thereafter to 5 years after surgery. Coronary angiography was performed
      at 5 years postoperatively. RESULTS: Operative mortality was 7.9% (5 of 63).
      Echocardiograms performed before discharge demonstrated a significantly improved
      LV ejection fraction that was maintained at 5 years, significantly decreased
      early postoperative LV end-diastolic and end-systolic volume indexes that were
      slightly increased at 1 year and then maintained at 5 years, and early
      postoperative decrement of the stroke volume index that had disappeared at 1 year
      and had not reappeared by 5 years. Postoperative myocardial single photon
      emission computed tomography showed an LV ejection fraction that had gradually
      improved until 2 years and was maintained at 5 years, significantly decreased LV
      end-diastolic and end-systolic volume indexes that were maintained at 5 years,
      and a stroke volume index that was unchanged until 2 years and slightly increased
      at 3 to 4 years. The arterial graft patency rate in the left coronary territory
      was 95.7% (67 of 70) at 5 years. The 10-year overall survival and adverse event
      free rate were 59.2% and 61.2%, respectively. CONCLUSIONS: Improved LV ejection
      fraction and reduced volume indexes were maintained and the stroke volume index
      had not decreased at 5 years after the procedure. Preserved patency of the
      arterial grafts might have an important role in maintaining improved LV function.

PMID- 24284231
TI  - Long survival in patients with leigh syndrome and the m.10191T>C mutation in MT
      ND3 : a case report and review of the literature.
AB  - We report an unusual case of Leigh syndrome due to the m.10191T>C mutation in the
      complex I gene MT-ND3. This mutation has been associated with a spectrum of
      clinical phenotypes ranging from infant lethality to adult onset. Despite
      infantile onset and severe symptoms, our patient has survived to early adulthood
      because of a strict dietary regimen and parental care. This patient is an extreme
      example of the frequently prolonged course of Leigh syndrome due to this
      particular mutation. 

PMID- 24284232
TI  - Primary diffuse leptomeningeal gliomatosis mimicking tuberculous meningitis.
AB  - Primary diffuse leptomeningeal gliomatosis is a disease with an aggressive course
      that can result in death. To date, 82 cases have been reported. Here, the case of
      a 3-year-old male patient presenting with strabismus, headache, and restlessness
      is reported. Physical examination revealed paralysis of the left abducens nerve,
      neck stiffness, and bilateral papilledema. Tuberculous meningitis was tentatively
      diagnosed, and antituberculosis treatment was initiated when cranial imaging
      revealed contrast enhancement around the basal cistern. Craniocervical magnetic
      resonance imaging (MRI) was performed when there was no response to treatment,
      and it revealed diffuse leptomeningeal contrast enhancement around the basilar
      cistern, in the supratentorial and infratentorial compartments, and in the spinal
      region. Primary diffuse leptomeningeal gliomatosis was diagnosed by a meningeal
      biopsy. 

PMID- 24284233
TI  - Assessment of clinical factors associated with a successful catheter ablation
      outcome in younger patients with atrial fibrillation.
AB  - BACKGROUND: Catheter ablation is now an alternative approach to antiarrhythmic
      drug therapy for patients with symptomatic atrial fibrillation (AF). We focused
      on younger patients in whom the prevalence of AF is low, and we sought clinical
      factors associated with unsuccessful ablation outcomes. METHODS AND RESULTS:
      Among 1983 consecutive symptomatic patients who underwent AF ablation procedures,
      95 patients (4.8%), age <= 40 years, were prospectively included. Of them, 64 had
      paroxysmal AF, and the remaining 31 had persistent AF. All patients underwent
      pulmonary vein isolation and cavotricuspid isthmus ablation. When AF recurred,
      redo ablations were performed if the patients desired. The mean number of
      ablation procedures was 1.3 +/- 0.6 times per patient. During the follow-up of 40
      [27.8-49.6] months, sinus rhythm was maintained in 86 patients (90.5%) without
      any antiarrhythmic drugs, but not in the remaining 9 patients (9.5%). Low body
      mass index (BMI) and persistent AF were associated with unsuccessful ablation
      procedures. In multivariate logistic regression analysis, a low BMI had the most
      significant value, with an odds ratio of 7.33 (p=0.022). The receiver operating
      characteristic curve demonstrated a BMI cut point of 22.1 kg/m(2), with an area
      under the curve of 0.773. CONCLUSION: In symptomatic younger AF patients, a low
      BMI was an independent clinical factor for unsuccessful AF ablation outcomes.

PMID- 24284235
TI  - [Spinal cord injury; damage control spine;whole procedure rehabilitation; stem
      cell transplantation; clinical treatment].

PMID- 24284234
TI  - Effectiveness of antipsychotic drugs against hostility in patients with
      schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) study.
AB  - INTRODUCTION: Aggressive behavior can be a dangerous complication of
      schizophrenia. Hostility is related to aggression. This study aimed to compare
      the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone
      on hostility in schizophrenia. METHODS: We used the data that were acquired in
      the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative
      Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at
      least minimal hostility (a score >= 2) at baseline. RESULTS: The primary analysis
      of hostility indicated an effect of difference between treatments (F(4,1487) =
      7.78, P < 0.0001). Olanzapine was significantly superior to perphenazine and
      quetiapine at months 1, 3, 6, and 9. It was also significantly superior to
      ziprasidone at months 1, 3, and 6, and to risperidone at months 3 and 6.
      DISCUSSION: Our results are consistent with those of a similar post-hoc analysis
      of hostility in first-episode subjects with schizophrenia enrolled in the
      European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine
      demonstrated advantages compared with haloperidol, quetiapine, and amisulpride.
      CONCLUSION: Olanzapine demonstrated advantages in terms of a specific
      antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE
      trial.

PMID- 24284236
TI  - [Standardization of diagnosis and treatment of acromegaly is imperative].

PMID- 24284237
TI  - [The comment of guidelines for clinical diagnosis and treatment of acromegaly -
      2013 update].

PMID- 24284238
TI  - [Update the sporadic cerebral amyloid angiopathy].

PMID- 24284239
TI  - [Lateral position one-stage combined anteroposterior approach versus posterior
      approach with subtotal corpectomy, decompression, and reconstruction of spine in
      the treatment of thoracolumbar burst fractures].
AB  - OBJECTIVE: To compare the medium and long-term outcomes of lateral position one
      stage plus anteroposterior versus posterior approach with subtotal corpectomy,
      decompression, and reconstruction of spine in the treatment of thoracolumbar
      burst fractures. METHODS: A total of 47 patients with thoracolumbar burst
      fractures were divided into 2 groups according to surgical approaches. Group A
      underwent lateral position one-stage plus anteroposterior approach while group B
      had posterior approach with subtotal corpectomy, decompression and reconstruction
      of spine. During a follow-up period of 36-68 months, their clinical and
      radiological outcomes were retrospectively evaluated. The perioperative volume of
      blood loss, operative duration, complications, pulmonary functions, Frankel scale
      and American Spinal Injury Association (ASIA) motor scores were recorded and
      analyzed. And the heights of anterior edge of vertebral body and Cobb angle were
      examined for radiological outcomes. RESULTS: At the latest follow-up, all
      patients achieved solid fusion with significant neurological improvements. The
      perioperative volumes of blood loss were less, operative duration was shorter and
      postoperative pulmonary functions were better in the group B (P < 0.05). The ASIA
      motor score and radiological outcomes were not significantly different at all
      timepoints between two groups (P < 0.05). But the neurological functions of two
      groups improved by approximately 1.4 Frankel grade (group A) versus 1.41 (group
      B) at the final follow-up. CONCLUSION: Lateral position one-stage plus
      anteroposterior and posterior approaches with subtotal corpectomy, decompression,
      and reconstruction of spine are adequate surgical treatments for thoracolumbar
      burst fractures. But the latter has the major advantages of less perioperative
      volume of blood loss, fewer complications, shorter operative duration and better
      pulmonary functions.

PMID- 24284240
TI  - [Unilateral versus bilateral pedicle fixation at the level of fracture in the
      treatment of thoracolumbar fractures with mild to moderate instability].
AB  - OBJECTIVE: To evaluate the efficacies of unilateral versus bilateral pedicle
      screw fixation through the pedicle of fractured vertebra plus short-segment
      pedicle instrumentation (SSPI) in the treatment of thoracolumbar fractures.
      METHODS: Between June 2008 and September 2010, a total of 46 patients with
      fractures of thoracolumbar junction, whose scores of load sharing classification
      (LSC) ranging from 5 to 7, underwent the combined treatment of SSPI and fracture
      level pedicle screw at our department. They were divided into 2 groups. Group I
      included 25 patients undergoing SSPI plus unilateral pedicle screw fixation
      through the pedicle of fractured vertebra (5 screws) while Group II included 21
      patients had SSPI plus bilateral pedicle screw fixation through the pedicle of
      fractured vertebra (6 screws). The data of anterior body height compression
      (AVHC), sagittal Cobb's angle, internal fixation failure, restoration of nervous
      function, visual analogue score (VAS) and Oswestry disability index (ODI) were
      analyzed. RESULTS: The groups were similar with regards to age, gender, LSC, AVHC
      and sagittal Cobb's angle preoperatively. Blood loss volume and operative
      duration were less in the Group I (109.2 +/- 30.68 vs 110.0 +/- 32.06 min, t = 
      0.086, P > 0.05 and 376.0 +/- 303.1 vs 409.5 +/- 361.1 ml, t = -0.342, P > 0.05).
      They were followed up for a minimum period of 12 months. In follow-up period was
      17.48 +/- 4.14 months in Group I versus 18.33 +/- 4.31 months in Group II (t = 
      0.683, P > 0.05). All patients with initial partial neurologic deficits improved
      at the final follow-up. Radiographic parameters and clinical outcomes were
      similar in both groups. CONCLUSIONS: Pedicle screw fixation through the pedicle
      of fractured vertebra plus SSPI is an excellent surgical therapeutic choice for
      patients with a LSC range of 5-7 thoraclumbar fractures. The efficacies of
      unilateral and bilateral pedicle screw fixation at fracture level are the same.

PMID- 24284241
TI  - [Surgical treatment strategies of odontoid fractures].
AB  - OBJECTIVE: To explore the characteristics of both odontoid fractures and adjacent
      section instability so as to devise proper surgical strategies and achieve better
      curative effect. METHODS: A total of 37 patients (including 26 males and 11
      females) with odontoid fractures treated from January 2005 to June 2012 with a
      mean age of (21-65) 36 years were analyzed retrospectively. Among 25 cases of
      simple odontoid fractures, there were type II (n = 20) and low type III (n = 5).
      There were 12 cases of odontoid fractures with adjacent section instability with
      C1/2 instability (n = 6), C2/3 instability (n = 4) and C1/2 and C2/3 instability
      (n = 2). The Frankel scale was used to assess nerve function. There were Grade A
      (n = 1), Grade B (n = 2), Grade C (n = 3) and Grade D (n = 6) at preoperation.
      Treatment included anterior and/or posterior pedicle screw fixation for reducing
      fracture and stabilizing upper cervical vertebrae. The Japanese Orthopedic
      Association (JOA) standards were used to evaluate the therapeutic effect.
      According to Frankel grade, nerve functional restoration of spinal cord injury
      was gauged. Fracture healing, bone graft fusion and spinal stability were
      monitored by radiology or computed tomography. RESULTS: All patients underwent
      surgery safely without severe complications. The average follow-up period was 18
      (12-48) months. There was significant difference (t = 13.464, P = 0.000) in JOA
      score between pre-operation (12.11 +/- 2.09) and post-operation (15.36 +/- 3.17).
      And the rate of improvement was 90.8% +/- 11.6% and that of "excellent" or "good"
      98%. Degree 1-2 recovery of neural function was achieved in all except for 1 case
      of Frankel B. All patients were immobilized in a hard collar for 3 months
      postoperatively. Fusion occurred in all cases within a mean time of (3-6) 4.5
      months. Radiology confirmed a proper screw position at postoperation. There were
      no occurrences of such complications as loosening, displacement or breakage of
      internal fixations. CONCLUSION: Proper surgical approaches may be selected
      according to the characteristics of both odontoid fractures and adjacent section
      instability.

PMID- 24284242
TI  - [Efficacies of bone-marrow-derived mononuclear cells with a hydroxylapatite
      composite in the treatment of osteonecrosis of the femoral head].
AB  - OBJECTIVE: To evaluate the efficacies of core decompression and implantation of
      concentrated autologous bone marrow containing mononuclear cells (BMMCs) with
      porous hydroxylapatite composite in the treatment of osteonecrosis of the femoral
      head. METHODS: A total of 35 patients with 57 osteonecrosis hips with ARCO stage
      I, stage II and stage IIIA disease were treated by BMMCs with a porous
      hydroxylapatite composite. The mean age at surgery was 39.4 (26-58) years and the
      mean period of follow-up 28 (12-40) months. In the control group, cell-free
      porous hydroxylapatite composite was implanted into 17 patients (27 hips) with
      osteonecrosis of the femoral head and the outcomes were compared. RESULTS: At the
      last follow-up, postoperative Harris hip scores significantly increased in both
      groups (P < 0.0001). The magnitude of increase was significantly greater in the
      BMMCs group compared with the control group (28.3% +/- 0.9% vs 18.4% +/- 1.7%, P
      < 0.01). Postoperative visual analog scale (VAS) scores significantly decreased
      in both groups (P < 0.01). The magnitude of decrease was significantly greater in
      the BMMCs group compared with the control group (-70.2% +/- 2.1% vs -51.7% +/-
      2.9%, P < 0.001). The clinical success rate was significantly higher in the BMMCs
      group compared with the control group (75.4% vs 37.0%, P < 0.01). The
      radiological success rates were similar between the BMMCs and control groups
      (59.6% vs 40.7%, P = 0.1046). CONCLUSION: The combined regimen of core
      decompression and implantation of concentrated autologous BMMCs with porous
      hydroxylapatite composite appears to confer benefits in the treatment of in
      stages I-IIIA osteonecrosis of the femoral head.

PMID- 24284244
TI  - [Efficacy analysis of two surgical procedures of carotid endarterectomy in the
      treatment of carotid artery stenosis].
AB  - OBJECTIVE: To analyze the efficacy and safety of eversion carotid endarterectomy
      (eCEA) and carotid endarterectomy with patch angioplasty (pCEA) in the treatment
      of carotid artery stenosis. METHODS: The clinical data were collected and
      analyzed for the patients with carotid artery stenosis undergoing carotid
      endarterectomy at Department of Vascular Surgery, Peking Union Medical College
      Hospital from October 2009 to October 2012. According to two different surgical
      procedures, they were divided into 2 groups of eCEA and pCEA. RESULTS: A total of
      248 patients received a follow-up. Among 274 cases of endarterectomy, 101 cases
      of eCEA and 173 cases of pCEA were performed. No significant difference (P >
      0.05) existed between two groups in gender, age, risk factors, stenotic degree of
      carotid artery or ratio of bilateral lesions. The ratio of shunt (15.8%) and
      antibiotics (26.7%) application, the duration of operation (88 +/- 20) min,
      intraoperative blood loss (45 +/- 16) ml and the length of stay (16 +/- 4) days
      in the group eCEA were significantly lower than those of group pCEA (P < 0.05).
      There was no significant difference (P > 0.05) between two groups in the ratio of
      complications, surgery-related mortality, restenosis and ipsilateral stroke.
      CONCLUSION: Both surgical procedures are both safe and effective in the treatment
      of carotid artery stenosis. However eCEA offers potential advantages. The choice
      of a particular surgical procedure depends on the surgeon experience and specific
      circumstances of carotid artery lesions.

PMID- 24284243
TI  - [Endovascular repair for isolated iliac artery aneurysm].
AB  - OBJECTIVE: To evaluate the short and middle-term efficacies of endovascular
      repair for isolated iliac artery aneurysms (IIAAs). METHODS: Retrospective
      analyses were performed for the clinical and follow-up data of 27 patients
      undergoing endovascular repair at Department of Vascular Surgery, Affiliated
      Zhongshan Hospital, Fudan University from January 2008 to December 2012. For
      asymptomatic aneurysms, repair criterion was a diameter over 3 cm while under 3
      cm for symptomatic aneurysms. RESULTS: There were 19 asymptomatic and 8
      symptomatic cases. And 25 selective and 2 emergent operations were performed. The
      interventions included endovascular stent grafts (n = 17), coil embolization (n =
      1), both stent grafts and coils (n = 7) and hybrid operations (n = 2). Technical
      success was achieved in all cases. No delayed healing or infection of inguinal
      access sites occurred. In-stent thrombosis could be observed in 2 cases. Buttock
      claudication was observed in one case. Sexual dysfunction occurred in three
      cases. Endoleaks were confirmed by intraoperative digital subtraction angiography
      in three cases. There was no occurrence of colorectal ischemia or postoperative
      aneurysmal rupture. Patients were followed up for a mean period of 33 +/- 18
      months. One patient died of recurrent renal cell carcinoma. CONCLUSION:
      Endovascular repair of isolated iliac artery aneurysms provides good short and
      middle-term patency. It may become a first-choice for treating isolated iliac
      artery aneurysms in the future.

PMID- 24284245
TI  - [Stenting of subtotal conclusion of internal carotid artery and comparing the
      cerebral embolic load of proximal balloon protection device with distal filter
      protection device].
AB  - OBJECTIVE: To study the safety, efficacy and perioperative complications of
      endovascular therapy in the treatment of subtotal conclusion of internal carotid
      artery(ICA) in patients. To compare the cerebral embolic load of proximal balloon
      protection device versus distal filter protection device during the operation.
      METHODS: Review all the operations of stenting for subtotal conclusion of ICA in
      Xuanwu hospital. New cerebral infarction after stenting was assessed by diffusion
      weighted magnetic resonance imaging. Count the number of new ischemic lesions of
      every patient. RESULTS: 35 patients with subtotal conclusion of ICA received
      endovascular stenting. Proximal protective device was used for 21 patients.
      Distal protective device was used for 14 patients. All procedures succeeded. 32
      patients received the cerebral MRI 1 week before and within 48 hours after the
      operation. Compared with filter protection(n = 14), proximal balloon device(n =
      18) resulted in a significant reduction in the incidence of new cerebral
      infarction (6/18 vs 10/14, P = 0.03). The number of new cerebral ischemic lesions
      were significant reduced by proximal balloon device (1/18 vs 4/14, P = 0.0006) .
      There were no serious cardiovascular events in 35 patients during the operation
      and the following up 3 months. 3 patients had restenosis which was demonstrated
      by ultrasound of ICA at 3 months after stenting. CONCLUSIONS: Endovascular
      stenting may be a safe and valid method for the treatment of subtotal occlusion
      of ICA. For the stenting of subtotal occlusion of ICA, proximal balloon
      protection device as compared with filter protection may reduce the embolic load
      to the brain more effectively. The stenting of subtotal occlusion of ICA still
      needs the randomized trails to confirm the safety and validity.

PMID- 24284246
TI  - [Detection rates of atherosclerosis by carotid versus lower limb ultrasonography
      in newly diagnosed type 2 diabetics].
AB  - OBJECTIVE: To compare the detection rates of atherosclerosis by carotid versus
      lower limb ultrasound in newly diagnosed type 2 diabetics and analyze the
      relationship between atherosclerosis and cardio-cerebrovascular events. METHODS:
      A total of 148 newly diagnosed type 2 diabetics were recruited. Both carotid and
      lower extremity atherosclerosis were assessed by Doppler ultrasound. Diabetic
      atherosclerosis was defined as the presence of either carotid or lower extremity
      plaques in any of the above-mentioned arterial segments. A kappa value was
      computed to document the agreement between isolated carotid (or lower limb)
      atherosclerosis and diabetic atherosclerosis. The prevalence of cardio
      cerebrovascular events was compared among different distribution types of
      atherosclerosis. RESULTS: According to the diagnostic criteria, the prevalence of
      diabetic atherosclerosis was 66.2% in the newly diagnosed type 2 diabetes. Based
      on carotid or lower extremity ultrasound, the prevalence of diabetic
      atherosclerosis was 27.0% and 62.2% respectively in newly diagnosed type 2
      diabetes. The kappa values for the agreement between carotid/lower limb
      atherosclerosis and diabetic atherosclerosis were 0.32/0.91 (95% confidence
      interval 0.22-0.42 for carotid vs 0.84-0.98 for lower extremity). The combination
      of carotid and lower extremity arterial atherosclerosis was associated with a
      significantly increased detection rate of cardio-cerebrovascular events (26.5%)
      versus those with either carotid or lower extremity arterial atherosclerosis (0%
      and 10.3% respectively). CONCLUSION: The combination of carotid and lower
      extremity ultrasonography can more accurately reflect the atherosclerotic lesions
      in type 2 diabetes. Due to a higher prevalence of cardio-cerebrovascular events,
      type 2 diabetics with both carotid and lower extremity atherosclerosis should be
      managed more aggressively to reduce the risk of cardio-cerebrovascular events.

PMID- 24284247
TI  - [Coagulation and prothrombotic state parameters: clinical analysis in early
      pregnancy].
AB  - OBJECTIVE: To assess the changes in coagulation, thrombosis, anti-coagulation and
      fibrinolysis during early pregnancy. METHODS: A total of 105 gravidas with
      monocytic pregnancies between 10 and 12 weeks gestational age at Sun Yat-sen
      Memorial Hospital, Sun Yat-sen University during April 2005 to June 2009 were
      recruited for study group and another 82 non-pregnant women as control group.
      Coagulation parameters, including thrombin time (TT), activated partial
      thromboplastin time (APTT), prothrombin (PT) and fibrinogen (Fg), were measured.
      We also tested the prothrombotic state parameters, including prothrombin fragment
      1+2 (F1+2), thrombomodulin (TM), thrombin-antithrombin complex (TAT),
      antithrombin III(AT-III), GMP140, thromboxane B2 (TXB2), plasminogen activator
      inhibitor (PAI-2; performed by enzyme-linked immunosorbent assay) and D-dimer
      (D2; tested by latex turbidimetric immunoassay). RESULTS: Fg (4.00 vs 2.52 g/L),
      F1+2 (0.66 vs 0.31 nmol/L), TAT (179.95 vs 39.46 ug/L), GMP140 (9.42 vs 19.13
      ug/L), D2 (201.51 vs 125.02 ug/L) and PAI-2 (0.047 vs 0.006 g/L) were
      statistically different between the study and control groups (P < 0.01).
      CONCLUSIONS: The coagulation, fibrinolysis and anti-fibrinolysis functions of
      healthy pregnant women become enhanced during early pregnancy while anti
      coagulation function slightly increases. These four basic functions are balanced
      at a higher level so that the activation of platelets stays at a lower level.

PMID- 24284248
TI  - [Analysis of relationship between patients with chromosomal translocation and the
      outcome of pregnancy].
AB  - OBJECTIVE: To explore the relationship between chromosome translocation and their
      phenotypic effect by analyzing the patients with loss pregnancy and avoiding
      fetuses with chromosomal abnormalities. METHODS: A total of 3067 cases with
      infertility or loss pregnancy were recruited to receive chromosome examination
      during January 2005 to December 2011 at Center of Prenatal Diagnosis, Peking
      University People's Hospital. Retrospective study was used to analyze the
      chromosome karyotypes and infertility or loss pregnancy. RESULTS: In 72 cases of
      patients with chromosome translocation, there were 17 pregnancies with homology
      translocation in fetus. And the numbers of patients with loss pregnancy and sex
      apparatus malformations were 40 and 15 respectively. CONCLUSION: Chromosome
      translocation plays an important role in patients with loss pregnancy or
      infertility. And chromosome examination should be performed to exclude the
      possibility of chromosome abnormities in patients with obstinate infertility.

PMID- 24284249
TI  - [Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific
      enolase and S-100beta and postoperative cognitive function of elderly patients
      undergoing acute replacement of femoral head].
AB  - OBJECTIVE: To explore the effects of parecoxib sodium analgesia on serum
      concentrations of neuron-specific enolase (NSE) and S-100beta and postoperative
      cognitive function of elderly patients undergoing acute replacement of femoral
      head. METHODS: After the approval of institutional review board and the provision
      of informed consent, 80 patients over 70 years old, undergoing acute replacement
      of femoral head under combined spinal and epidural anesthesia and midazolam
      sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from
      January 2011 to May 2012, were randomly assigned into control group (group C, n =
      40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg
      (based on weight 50 kg) was administered via an intravenous injection after
      admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was
      given initially. Additional morphine 2 mg was given to maintain the pain visual
      analog scale (VAS) of 3 points or less in both groups. Primary observation
      indices: (1) postoperative time and additional amount of morphine; (2) rate of
      postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3
      days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of
      NSE and S-100beta were measured at the timepoints of before analgesia (t0),
      before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours
      postoperation (t3-t5); (4) other serious complications. RESULTS: Compared with
      group C, the additional amount of morphine, postoperative time, rate of POD and
      POCD at T1-T4, the level of NSE at t2-t5 and S-100beta at t1-t5 were lower in
      group P (P < 0.05). No other serious complications were observed. CONCLUSIONS:
      Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients
      with neuroprotective effects.

PMID- 24284250
TI  - [Clinical value of CT-guided (125)I brachytherapy for retroperitoneal metastatic
      lymph node from PHC].
AB  - OBJECTIVE: To discuss the clinical value of CT-guided (125)I brachytherapy with
      retroperitoneal metastatic lymph nodes from primary hepatic carcinoma(PHC).
      METHODS: Twenty patients with retroperitoneal metastatic lymph node recurrence
      from PHC were percutaneously treated by (125)I brachytherapy with computed
      tomographic (CT) guidance. The number, radioactive dose, placed position of
      radioactive seeds and puncture path were determined by computerized treatment
      planning system (TPS). The radioactive seeds were implanted when the needles were
      in right position by CT scan. Radiotherapy verification and quality assessment
      were performed after treatment by CT scan. Follow-up contrast material-enhanced
      CT were reviewed. RESULTS: The local control rate of 3, 6, 10, 15 months was
      70.0%, 56.3%, 44.4%, 25.0% respectively. There were no severe complications such
      as massive bleeding and radiation injury of normal tissues. CONCLUSION: CT-guided
      (125)I brachytherapy are effective and may be safely applied to retroperitoneal
      metastatic lymph nodes from PHC.

PMID- 24284251
TI  - [Study on the correlation of lower extremity arterial vessels by ultrasonography
      and atherosclerosis detection indicators].
AB  - OBJECTIVE: To examine the correlation between lower extremity artery ultrasound
      and arteriosclerosis detection indicators, including ankle-brachial index (ABI)
      and Cardiac Ankle Vascular Index (CAVI). METHODS: According to the level of lower
      extremity arterial disease by ultrasonography, 320 patients were divided into 3
      groups (normal group, mild lesions group and severe lesions group). Comparative
      analysis of the difference of arteriosclerosis detection indicators among the
      groups, including ABI and CAVI . To analyze the correlation of two test results
      and explore the risk factors of lower extremity atherosclerotic lesions. RESULTS:
      To compare ABI among the three groups, the differences were statistically
      significant (P < 0.05 ) . Lower extremity arterial disease was negatively
      correlated with ABI and positively correlated with CAVI (P = 0.000 ). Using
      Logistic regression analysis: age, gender, diabetes, pulse pressure is the impact
      of lower extremity arterial disease risk factors. CONCLUSION: ABI and CAVI can be
      used as reliable indicators for the screening of artery stenosis, occlusion and
      atherosclerosis, combined with color Doppler ultrasonography can improve the
      diagnosis rate of lower extremity arterial disease.

PMID- 24284253
TI  - [Effects of pericytes on the leakage of rat corneal neovascularization].
AB  - OBJECTIVE: To explore the effects of pericytes on the leakage of rat corneal
      neovascularization (CNV). METHODS: CNV was induced by micropocket assay in rats.
      Two eyes of the same rat were divided randomly into experimental and control
      groups. The experimental group received the VEGF + anti-PDGF-B pellet while the
      control group the VEGF + PBS pellet. Corneal samples were excised at Day 5
      postoperation. CNV leakage was measured by Evans blue method. Pericyte coverage
      index (MPI) was applied to quantify the pericyte coverage through double
      immunofluorescent stain of frozen sections of corneas with CD31 as endothelial
      and alpha-smooth muscle actin (alpha-SMA) as pericyte marker. Corneal weight was
      measured. RESULTS: In the control group, MPI was 56.5%, cornea weight (7.36 +/-
      0.56) mg and CNV permeability rate (0.24 +/- 0.07) ug*ml(-1)*mm(-2). In the
      experimental group, MPI was 11.3%, cornea weight (8.96 +/- 1.09) mg and CNV
      permeability rate (0.68 +/- 0.36) ug*ml(-1)*mm(-2). The intergroup difference was
      statistically significant (P MPI<0.01, P permeability= 0.01, P weight = 0.01).
      CONCLUSION: Pericytes inhibit the leakage of rat CNV. Such findings may guide the
      clinical management of hyperpermeability.

PMID- 24284252
TI  - [MR appearance of multifocal clear cell renal cell carcinoma].
AB  - OBJECTIVE: To document the magnetic resonance (MR) imaging features of multifocal
      clear cell renal cell carcinoma (RCC). METHODS: The MR findings of 11 cases of
      pathologically-proved multifocal clear cell RCCs were reviewed retrospectively
      from January 2008 to December 2010. All patients underwent MR in a 1.5 T or a 3.0
      T scanner. The MR features of the lesions were analyzed, with emphasis on the
      location, the signal intensity on T2-weighted imaging (T2WI), in regards to
      pseudocapsule, lipid component, hemorrhage, cystic degeneration, and enhancement
      pattern. Meanwhile, from these six aspects, the MR appearance of renal cell
      carcinomas occurring in the same patient were compared. RESULTS: 24 tumors (mean
      diameter, 3.1 cm) in the 11 patients (6 men, 5 women; age range, 36-69 years;
      mean age, 50.6 years) were detected. Multiple lesions in bilateral kidneys were
      found in 9 patients (9/11), while in unilateral kidney 2 patients (2/11).
      Hyperintensity on T2WI were observed in 16 lesions (16/24), while hypointensity 8
      lesions (8/24); pseudocapsule was seen in all lesions; hemorrhage in 4 lesions
      (4/24), lipid component in 12 lesions (12/24) and cystic degeneration in 18
      lesions (18/24), persistent enhancement in 22 lesions (22/24) and rapid wash-out
      pattern in 2 lesions (2/24). All lesions showed moderate or intense enhancement.
      The MR appearances of lesions in the same patient were identical in 5 cases
      (5/11), different in 6 cases (6/11). CONCLUSION: Multifocal clear cell RCCs occur
      more commonly in bilateral kidneys simultaneously than in unilateral kidney. The
      lesions in the same patient can show different MR imaging features, which
      probably facilitate the preoperative determination.

PMID- 24284254
TI  - [Up-regulator of cell proliferation predicts poor prognosis in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To explore the potential value of up-regulator of cell proliferation
      (URGCP) as a biomarker for predicting the prognosis of hepatocellular carcinoma
      (HCC). METHODS: The expression of URGCP was analyzed in 15 HCC cell lines and in
      10 pairs of HCC and adjacent tissues with reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. The expression of URGCP in 278 paraffin
      embedded, archived clinical HCC samples was analyzed by immunohistochemistry
      (IHC) and statistic analysis conducted to examine the relationship of prognosis
      and URGCP expression. RESULTS: IHC analysis revealed a high expression of URGCP
      in all HCC cell lines and in 122/278 (43.8%) paraffin-embedded archived HCC
      specimens. The expression level of URGCP was significantly correlated with
      clinical staging and poor patient survival of HCC in the study cohort and in
      various clinical subgroups, but not correlated with HCC patient age, tumor size,
      tumor number or alpha-fetoprotein level. CONCLUSION: URGCP plays an important
      role in promoting the proliferation and tumorigenesis of HCC and may represent a
      novel prognostic biomarker and therapeutic target for the disease.

PMID- 24284255
TI  - Evaluation of piezoelectric material properties for a higher power output from
      energy harvesters with insight into material selection using a coupled
      piezoelectric-circuit-finite element method.
AB  - Piezoelectric material properties have substantial influence on electrical power
      output from piezoelectric energy harvesters (PEHs). Understanding their
      influences is the first step in designing effective PEHs to generate higher power
      outputs. This paper uses a coupled piezoelectric-circuit-finite element method to
      study the power outputs of different types of piezoelectric materials, including
      single crystal, polyvinylidene fluoride (PVDF), and soft and hard lead zirconate
      titanate (PZT) materials. The purpose of this study is to try to gain an
      understanding of which piezoelectric material property--the elastic compliance
      s11, the piezoelectric strain constant d31, the piezoelectric stress constant
      g31, and the relative dielectric constant epsilon(T)r33, and the associated
      material properties of the d31 * g31, called the figure of merit (FOM), and the
      coupling coefficient k31--dominates the power output. A rectangular piezoelectric
      plate under a low-frequency excitation is used to evaluate piezoelectric material
      properties for a higher power output. It was found that 1) d31 is a more dominant
      material property over other material properties for higher power output; 2) FOM
      was more linearly related to the power output than either the k31 or the d31; and
      3) epsilon(T)r33 had some role; when the materials have an identical d31; a lower
      epsilon(T)r33 was preferred. Because of unexplained outliers, no single material
      parameter was able to be recommended as selection criteria, but combined FOM with
      d31 parameters is recommended for selection of piezoelectric material for a
      higher power output from PEHs.

PMID- 24284256
TI  - Augmentation of clozapine with amisulpride: an effective therapeutic strategy for
      violent treatment-resistant schizophrenia patients in a UK high-security
      hospital.
AB  - OBJECTIVE: Clozapine is used in the management of treatment-resistant
      schizophrenia and is effective in reducing aggression; however a subgroup of
      patients is poorly responsive. For violent patients in this group, there is
      limited literature on the use of strategies to augment clozapine with other
      agents. Here we present a case series of 6 schizophrenia patients, within a high
      security hospital, who have a history of serious violence and who were treated
      with clozapine augmented with amisulpride. METHODS: We reviewed case notes and
      health records for evidence of violence/aggression and positive factors such as
      engagement in activities, and Clinical Global Impression (CGI) scores were
      formulated. We also examined metabolic parameters before and after augmentation.
      RESULTS: All 6 of the patients showed clinical improvement in symptoms and a
      reduction in their risk of violence to others. Five patients had a reduction in
      number of violent/aggressive incidents, and all patients showed improvement in
      engagement in occupational, vocational, and/or psychological work. Metabolic
      parameters were largely unchanged except for 1 patient whose Body Mass Index
      (BMI) increased. Five patients reported side effects as unchanged or improved.
      CONCLUSION: These schizophrenia patients with a history of violence showed
      clinical improvement and reduced aggression and violence with amisulpride
      augmentation of clozapine. To our knowledge, this is the first report of an
      antiaggressive benefit of this combination in forensic psychiatric patients.
      Further studies are warranted to establish the efficacy and anti-aggressive
      effects of amisulpride augmentation of clozapine.

PMID- 24284257
TI  - Anti-bacterial and anti-inflammatory properties of capric acid against
      Propionibacterium acnes: a comparative study with lauric acid.
AB  - BACKGROUND: Propionibacterium acnes (P. acnes) is a commensal bacterium which is
      possibly involved in acne inflammation. The saturated fatty acid, lauric acid
      (C12:0) has been shown to possess antibacterial and anti-inflammatory properties
      against P. acnes. Little is known concerning the potential effects of its
      decanoic counterpart, capric acid (C10:0). OBJECTIVE: To examine the
      antibacterial and anti-inflammatory activities of capric acid against P. acnes
      and to investigate the mechanism of the anti-inflammatory action. METHODS: The
      antimicrobial activity of fatty acids was detected using the broth dilution
      method. An evaluation of P. acnes-induced ear edema in mice was conducted to
      evaluate the in vivo anti-inflammatory effect. To elucidate the in vitro anti
      inflammatory effect, human SZ95 sebocytes and monocytic THP-1 cells were treated
      with P. acnes alone or in the presence of a fatty acid. The mRNA levels and
      secretion of pro-inflammatory cytokines were measured by qRT-PCR and enzyme
      immunoassay, respectively. NF-kappaB activation and MAPK expression were analyzed
      by ELISA and Western blot, respectively. RESULTS: Lauric acid had stronger
      antimicrobial activity against P. acnes than capric acid in vitro and in vivo.
      However, both fatty acids attenuated P. acnes-induced ear swelling in mice along
      with microabscess and significantly reduced interleukin (IL)-6 and CXCL8 (also
      known as IL-8) production in P. acnes-stimulated SZ95 sebocytes. P. acnes-induced
      mRNA levels and secretion of IL-8 and TNF-alpha in THP-1 cells were suppressed by
      both fatty acids, which inhibited NF-kappaB activation and the phosphorylation of
      MAP kinases. CONCLUSION: Our data demonstrate that both capric acid and lauric
      acid exert bactericidal and anti-inflammatory activities against P. acnes. The
      anti-inflammatory effect may partially occur through the inhibition of NF-kappaB
      activation and the phosphorylation of MAP kinases.

PMID- 24284258
TI  - Lithium or an atypical antipsychotic drug in the management of treatment
      resistant depression: a systematic review and economic evaluation.
AB  - BACKGROUND: Patients with treatment-resistant depression (TRD) are those with
      major depressive disorder that has not responded adequately to treatment. The
      causes of depression are not fully understood, although there is evidence to
      suggest that depression is a complex interaction among biological, genetic,
      psychosocial and environmental factors. Strategies available for the treatment of
      patients with TRD include pharmacological, non-pharmacological, and psychological
      and psychosocial interventions. Pharmacological treatment options include
      switching to a different antidepressant, the addition of another antidepressant
      of a different class, or use of an augmenting agent, such as anticonvulsants,
      lithium or atypical antipsychotics (AAPs). However, there is limited evidence
      available on the effectiveness of these strategies in the treatment of TRD.
      OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of
      augmentation of selective serotonin reuptake inhibitor (SSRI) antidepressant
      therapy with either lithium or an AAP drug in the management of people with
      treatment-resistant unipolar depression, defined as failure to respond to two or
      more antidepressant drugs in their current episode of depression. DATA SOURCES:
      Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL),
      EMBASE, MEDLINE, PsycINFO and NHS Economic Evaluation Database (NHS EED). All
      databases were searched from inception to August 2011. Additional data were
      obtained from manufacturers. REVIEW METHODS: Systematic reviews of studies
      evaluating clinical effectiveness, economic analyses and quality of life (QoL)
      were executed. Quality assessment according to predefined criteria was undertaken
      independently by two reviewers. Pairwise meta-analyses and mixed-treatment
      comparisons (MTCs) using both fixed- and random-effects models were undertaken
      based on intention-to-treat analyses. A probabilistic de novo mathematical model
      was developed to synthesise the available data on costs and clinical outcomes
      from the UK NHS perspective over a 1-year time horizon (8 weeks of acute
      treatment captured by a decision tree and 10 months of maintenance treatment
      captured by a Markov model). RESULTS: Twelve randomised controlled trials (RCTs)
      were identified in the review of clinical effectiveness literature; 10 considered
      SSRI  +  AAP compared with SSRI  +  placebo/no treatment, one considered SSRI  + 
      AAP compared with SSRI  +  lithium and one considered SSRI  +  lithium compared
      with SSRI  +  placebo. The RCTs included in the primary analyses used fluoxetine
      as the background SSRI and olanzapine as the AAP. Results of the MTC showed a non
      significant trend in favour of lithium augmentation for response [lithium a
      priori odds ratio (OR) 1.29; 95% credible interval (CrI) 0.11 to 5.32; lithium
      post hoc OR 4.15; 95% CrI 0.25 to 20.34 (the trial informing the comparison with
      lithium reported response using two different definitions)], mean change in
      Montgomery-Asberg Depression Rating Scale score from baseline (mean difference - 
      1.47, 95% CrI -  9.10 to 6.41) and all-cause withdrawals (OR 0.74, 95% CrI 0.10
      to 2.66). Four economic evaluations (none directly addressing the review
      question) and 17 studies that reported on QoL were identified and summarised in
      narrative reviews. The results of the de novo modelling indicate that
      augmentation of SSRI with lithium dominates augmentation of an SSRI with AAP
      (i.e. it resulted in cost savings of L905 per person per year and generated more
      health benefits, estimated to be 0.03 quality-adjusted life-years). However,
      sensitivity analyses showed that the model was highly sensitive to changes in
      acute treatment efficacy (response and remission) or discontinuation. The model
      was not sensitive to changes in other parameters. LIMITATIONS: In patients with
      TRD, there is a lack of direct evidence comparing the clinical effectiveness of
      augmenting an SSRI with an AAP compared with augmenting with lithium. RCTs were
      identified which facilitated comparison of adding AAP with adding lithium via a
      MTC. However, variations in the definitions of response implemented in the RCTs,
      together with differences in patient baseline characteristics across RCTs,
      introduce bias into the analysis. The direction and extent of the bias is
      uncertain. CONCLUSIONS: Augmentation of SSRIs with lithium or AAP is likely to be
      beneficial in people with TRD. Clinical evaluation based on the limited evidence
      identified in this research indicates no statistically significant difference
      between the two augmentation strategies. Cost-effectiveness analyses suggest that
      augmentation with lithium is less expensive and more effective than augmentation
      with AAP. However, the uncertainty in the clinical estimates of discontinuation
      and treatment response is reflected in the model results. A RCT comparing the two
      augmentation strategies, reporting relevant outcomes, including QoL, is needed.
      STUDY REGISTRATION: PROSPERO CRD42011001464.

PMID- 24284259
TI  - Can the hydrophilicity of functional monomers affect chemical interaction?
AB  - The number of carbon atoms and/or ester/polyether groups in spacer chains may
      influence the interaction of functional monomers with calcium and dentin. The
      present study assessed the chemical interaction and bond strength of 5 standard
      synthesized phosphoric-acid ester functional monomers with different spacer chain
      characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x
      ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile
      bond strength (MUTBS). The tested functional monomers were 2-MEP (two-carbon
      spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic
      polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer).
      The intensity of monomer-calcium salt formation measured by AAS differed in the
      order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer
      treated dentin surfaces showed resistance to rinsing for all monomer-dentin
      bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP.
      Highest uTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP)
      of phosphate functional monomers induced formation of unstable monomer-calcium
      salts, and lower chemical interaction and dentin bond strength. The presence of
      ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may
      affect the hydrophilicity, MUTBS, and also the formation of monomer-calcium
      salts.

PMID- 24284260
TI  - The influence of hydrolysis induced biopolymers from recycled aerobic sludge on
      specific methanogenic activity and sludge filterability in an anaerobic membrane
      bioreactor.
AB  - The objective of the present study was to evaluate the impact of excess aerobic
      sludge on the specific methanogenic activity (SMA), in order to establish the
      maximum allowable aerobic sludge loading. In batch tests, different ratios of
      aerobic sludge to anaerobic inoculum were used, i.e. 0.03, 0.05, 0.10 and 0.15,
      showing that low ratios led to an increased SMA. However, the ratio 0.15 caused
      more than 20% SMA decrease. In addition to the SMA tests, the potential influence
      of biopolymers and extracellular substances, that are generated as a result of
      excess aerobic sludge hydrolysis, on membrane performance was determined by
      assessing the fouling potential of the liquid broth, taking into account
      parameters such as specific resistance to filtration (SRF) and supernatant
      filterability (SF). Addition of aerobic sludge to the anaerobic biomass resulted
      in a high membrane fouling potential. The increase in biopolymers could be
      ascribed to aerobic sludge hydrolysis. A clear positive correlation between the
      concentration of the colloidal fraction of biopolymer clusters (cBPC) and the SRF
      was observed and a negative correlation between the cBPC and the SF measured at
      the end of the above described SMA tests. The latter implies that sludge
      filtration resistance increases when more aerobic sludge is hydrolyzed, and thus
      more cBPC is released. During AnMBR operation, proteins significantly contributed
      to sludge filterability decrease expressed as SRF and SF, whereas the
      carbohydrate fraction of SMP was of less importance due to low concentrations. On
      the contrary, carbohydrates seemed to improve filterability and diminish SRF of
      the sludge. Albeit, cBPC increase caused an increase in mean TMP during the AnMBR
      operation, confirming that cBPC is positively correlated to membrane fouling. 

PMID- 24284261
TI  - Compulsivity and impulsivity-personal reflections: why now and why here?
AB  - This issue of CNS Spectrums contains a unique collection of manuscripts that
      examine compulsivity and impulsivity from a broad range of perspectives and helps
      to shape our evolving understanding of compulsivity and impulsivity as orthogonal
      symptom dimensions arising from parallel tightly regulated brain circuits giving
      rise to a spectrum of overlapping diagnostic categories. 

PMID- 24284262
TI  - Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment
      induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor
      modulation.
AB  - Depressed patients suffer from cognitive dysfunction, including memory deficits.
      Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients.
      The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5
      HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A
      receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in
      normal rats in novel object recognition (NOR) and conditioned fear (Mork et al.,
      2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved
      in its memory effects, and therefore investigated these effects in 5-HT depleted
      rats. Four injections of the irreversible tryptophan hydroxylase inhibitor 4
      chloro-dl-phenylalanine methyl ester hydrochloride (PCPA, 86mg/kg, s.c.) induced
      5-HT depletion, as measured in hippocampal homogenate and microdialysate. The
      effects of acute challenge with vortioxetine or the 5-HT releaser fenfluramine on
      extracellular 5-HT were measured in PCPA-treated and control rats. PCPA's effects
      on NOR and spontaneous alternation (SA) performance were assessed along with the
      effects of acute treatment with 5-hydroxy-l-tryptophan (5-HTP), vortioxetine, the
      selective 5-HT reuptake inhibitor escitalopram, or the 5-HT norepinephrine
      reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo
      autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate,
      and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed
      these deficits. At similar SERT occupancies (>90%) vortioxetine, but not
      escitalopram or duloxetine, restored memory performance. Acute fenfluramine
      significantly increased extracellular 5-HT in control and PCPA-treated rats,
      while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT
      depletion impaired memory performance in rats through one or more of its receptor
      activities. 

PMID- 24284263
TI  - Verrucous hemangioma with pseudoepitheliomatous epidermal hyperplasia in an adult
      horse.
AB  - Verrucous hemangiomas are a rare specific variant of equine skin tumors not well
      described in the literature. An 8-year-old gelding presented a unilateral lesion
      on the pastern. Macroscopically, the mass showed a warty and verrucous surface
      with focal ulcerations. The histology showed a dermal proliferation of
      endothelial-layered capillaries and venules separated by a delicate stroma of
      scant fibroblasts and collagen deposition, with pseudoepitheliomatous hyperplasia
      (exuberant reactive irregular epithelial hyperplasia with tongue-like projections
      extending into the dermis, mimicking downgrowth of squamous cell carcinoma) and
      orthokeratotic hyperkeratosis of the overlying epidermis. The immunohistochemical
      study confirmed the endothelial origin of the tumor, and a final diagnosis of
      verrucous hemangioma with pseudoepitheliomatous hyperplasia was confirmed. To the
      knowledge of the authors, this is the first detailed description of this entity
      in adult horses. Moreover, the clinical progression and epidermal changes have
      not been previously reported, emphasizing the importance of a pathological study
      of any epithelial preneoplastic lesion to rule out an underlying dermal
      neoplasia. 

PMID- 24284264
TI  - A methodology for the sustainability assessment of arsenic mitigation technology
      for drinking water.
AB  - In this paper we show how the process analysis method (PAM) can be applied to
      assess the sustainability of options to mitigate arsenic in drinking water in
      rural India. Stakeholder perspectives, gathered from a fieldwork survey of 933
      households in West Bengal in 2012 played a significant role in this assessment.
      This research found that the 'most important' issues as specified by the
      technology users are cost, trust, distance from their home to the clean water
      source (an indicator of convenience), and understanding the health effects of
      arsenic. We show that utilisation of a technology is related to levels of trust
      and confidence in a community, making use of a composite trust-confidence
      indicator. Measures to improve trust between community and organisers of
      mitigation projects, and to raise confidence in technology and also in fair
      costing, would help to promote successful deployment of appropriate technology.
      Attitudes to cost revealed in the surveys are related to the low value placed on
      arsenic-free water, as also found by other investigators, consistent with a lack
      of public awareness about the arsenic problem. It is suggested that increased
      awareness might change attitudes to arsenic-rich waste and its disposal
      protocols. This waste is often currently discarded in an uncontrolled manner in
      the local environment, giving rise to the possibility of point-source
      recontamination. 

PMID- 24284265
TI  - Prevalence of communication disorders in HIV-infected adults.
AB  - Few adult patients with HIV/AIDS are evaluated for communication disorders. A
      broad inventory of the communication disorders was obtained in a convenience
      sample of 82 adult HIV/AIDS patients who presented for medical appointments. Each
      participant underwent a head and neck exam and a communications skills
      evaluation. Speech, language, and cognition were assessed using a 10-item test
      battery. A 14-item hearing test battery was conducted in a separate session. The
      primary outcomes were the presence and degree of communication disorders. Head
      and neck exams revealed 40% with ear-related issues. Only 2 participants showed
      normal findings on all 24 communication skills assessments. Four demonstrated
      normal findings on all speech-language-cognitive assessments, whereas 8 had
      normal findings on the complete hearing test battery. A relatively high
      prevalence of cognitive and language deficits and central auditory disturbances
      were found. Clinicians must recognize the potential for communication deficits
      even in a relatively healthy patient with HIV. 

PMID- 24284266
TI  - High-resolution radial distribution function of pure ion-implanted amorphous
      silicon measured using tilted-illumination selected-area electron diffraction.
AB  - High-resolution radial distribution functions of as-implanted and thermally
      relaxed amorphous silicon created by ion implantation were measured using tilted
      illumination selected area electron diffraction at room temperature. The
      diffracted intensities were measured out to a maximum scattering vector 2
      sin(theta)/lambda of 3.3-3.7 A-1. The volume-averaged pair-correlation statistics
      of as-implanted and relaxed ion-implanted amorphous silicon are virtually
      indistinguishable with coordination numbers of 3.7 +/- 0.3 and 3.9 +/- 0.3 (for
      neighbors closer than 3 A) and average bond angles of 109 +/- 0.5 degrees  and
      110 +/- 0.6 degrees , respectively. The atomic rearrangements in ion-implanted
      amorphous silicon due to a low temperature anneal are subtle.

PMID- 24284267
TI  - Screening cultures for detection of methicillin-resistant Staphylococcus aureus
      in a population at high risk for MRSA colonisation: identification of optimal
      combinations of anatomical sites.
AB  - This retrospective study analysed the diagnostic yield of single-site, two-site,
      and three-site anatomical surveillance cultures in a population of 4,769 patients
      at high risk for methicillin-resistant Staphylococcus aureus (MRSA) colonisation.
      Cultures of seven anatomical sites were used as the gold standard against which
      to measure the sensitivity of MRSA detection. Detection rates for the seven
      single-sites, 21 two-site, and 35 three-site combinations are presented. Single
      site swabbing only detected 50.5% (nose) of total cases, while three-site
      surveillance achieved a 92% (groin + nose + throat) sensitivity of detection at
      best. It is recommended that at least three anatomical sites should be screened
      for MRSA colonisation in these high-risk patients. 

PMID- 24284269
TI  - Scoliosis: review of types of curves, etiological theories and conservative
      treatment.
AB  - BACKGROUND: Scoliosis is the deviation in the normal vertical spine. Although
      there are numerous studies available about treatment approaches for scoliosis,
      the numbers of studies that talk about its etiology and pathology are limited.
      OBJECTIVE: Aim of this study was to discuss the different types of scoliosis; its
      curves and etiological theories; and to note their implication on its treatment.
      METHODS: We examined various electronic databases including Pub MED, Medline,
      Cinhal, Cochrane library and Google scholar using key words "scoliosis",
      "etiology", "pathology" and "conservative treatment". References of obtained
      articles were also examined for cross references. The search was limited to
      articles in English language. RESULTS: A total of 145 papers, about Prevalence,
      History, Symptoms, classification, Biomechanics, Pathogenesis, Kinematics and
      Treatment of scoliosis were identified to be relevant. CONCLUSION: To choose the
      appropriate treatment approach for scoliosis we need to understand its etiology
      and pathogenesis first. Early intervention with conservative treatment like
      physiotherapy and bracing can prevent surgery.

PMID- 24284271
TI  - Pathoanatomical characteristics of clinical lumbar spinal stenosis.
AB  - BACKGROUND: There is no clear picture of pathoanatomy in clinically diagnosed
      LSS. Findings in the literature regarding imaging in LSS are heterogeneous.
      OBJECTIVE: Characterize the pathoanatomy of LSS, as reported in the radiology
      reports, for a large community-based sample of patients with the clinical
      diagnosis of LSS. METHODS: Retrospective review of clinical radiology reports.
      The sample comprised patients 40 years of age or older, with clinically diagnosed
      LSS. Radiology reports for lumbar MRI were obtained and data were extracted
      pertaining to the type and location of LSS. RESULTS: 173 subjects with a mean age
      of 66.2 +/- 11.7 years were included (61% women). 68.2% had mixed stenosis, 19.1%
      had central stenosis only, and 12.7% had lateral stenosis only. By level, the
      most prevalent findings were at L4/5 (93%), L3/4 (66%) and L5/S1 (49%). This
      pattern was different in those with lateral stenosis only, where the proportion
      of findings at L5/S1 was higher than at L3/4. 156 subjects (90.2%) had findings
      of at least moderate severity. Considering moderate-severe findings only, 31% had
      mixed stenosis and 40.0% had multi-level findings (90.5% at adjacent segments).
      When mild findings were included for subjects with at least one moderate-severe
      finding the rate of mixed stenosis increased to 59%, and multi-level stenosis to
      68.6%. The most common multi-level combinations were L3/4 and L4/5 for two-level
      stenosis and L2/3 through L4/5 for three-level. CONCLUSION: Results of this study
      confirm a number of pathoanatomical patterns in people diagnosed with LSS,
      including a high proportion of stenosis at L4/5, followed by L3/4 and L5/S1.
      Results also suggest a high prevalence of multi-level stenosis at adjacent
      segments. The prevalence of mixed stenosis varied from 31% to 68.2%; inclusion of
      mild findings resulted in a higher rate of both mixed and multi-level stenosis,
      compared to analysis of moderate-severe findings only. These results may guide
      future studies on LSS pathophysiology, by focusing attention toward the most
      prevalent radiological findings.

PMID- 24284270
TI  - Femoral cartilage thickness measurements in healthy individuals: learning,
      practicing and publishing with TURK-MUSCULUS.
AB  - BACKGROUND AND OBJECTIVES: Measurement of the femoral cartilage thickness by
      using in-vivo musculoskeletal ultrasonography (MSUS) has been previously shown to
      be a valid and reliable method in previous studies; however, to our best notice,
      normative data has not been provided before in the healthy population.The aim of
      our study was to provide normative data regarding femoral cartilage thicknesses
      of healthy individuals with collaborative use of MSUS. METHODS: This is across
      sectional study run at Physical and Rehabilitation Medicine Departments of 18
      Secondary and Tertiary Centers in Turkey. 1544 healthy volunteers (aged between
      25-40 years) were recruited within the collaboration of TURK-MUSCULUS (Turkish
      Musculoskeletal Ultrasonography Study Group). Subjects who had a body mass index
      value of less than 30 and who did not have signs and symptoms of any
      degenerative/inflammatory arthritis or other rheumatic diseases, history of knee
      trauma and previous knee surgery were enrolled. Ultrasonographic measurements
      were performed axially from the suprapatellar window by using linear probes while
      subjects' knees were in maximum flexion. Three (mid-point) measurements were
      taken from both knees (lateral condyle, intercondylar area, medial condyle).
      RESULTS: A total of 2876 knees (of 817 M, 621 F subjects) were taken into
      analysis after exclusion of inappropriate images. Mean cartilage thicknesses were
      significantly lower in females than males (all p< 0.001). Thickness values
      negatively correlated with age; negatively (females) and positively (males)
      correlated with smoking. Men who regularly exercised had thicker cartilage than
      who did not exercise (all p < 0.05). Increased age (in both sexes) and absence of
      exercise (males) were found to be risk factors for decreased cartilage
      thicknesses. CONCLUSION: Further data pertaining to other countries would be
      interesting to uncover whether ethnic differences also affect cartilage
      thickness. Collaborative use of MSUS seems to be promising in this regard.

PMID- 24284272
TI  - Effects of Kinesio(r) Tape in low back muscle fatigue: randomized, controlled,
      doubled-blinded clinical trial on healthy subjects.
AB  - BACKGROUND: Muscle fatigue of the trunk extensor musculature plays a considerable
      role in chronic low back pain (LBP). The underlying physiology of fatigue is
      complex and not fully understood. The Kinesio(r) Taping (KT) supports damaged
      structures while allowing mobility and at the same time may influence some of the
      mechanisms associated with muscle fatigue such as blood flow and proprioception.
      OBJECTIVE: The aim of this study is to determine the influence of KT on the
      resistance to fatigue of the lumbar extensor musculature in a sample of young
      healthy subjects. METHODS: A randomized, controlled, doubled-blinded clinical
      trial was conducted. Ninety nine healthy subjects were randomized in to the three
      arms of the study Kinesio(r) Tape (KT), placebo (P) and control (C). Directly
      after application of KT we measured lumbar extensor musculature endurance with
      the Biering-Sorensen test. Subjects and researchers were blinded to the
      intervention. Time achieved (seconds) was compared between groups with one-way
      ANOVA with confidence intervals of 95%. RESULTS: There were significant
      differences between the time achieved in the KT group versus the control group (p
      < 0.05). The placebo group performed better than the control group but worse than
      the KT group, these were not significant in either case. CONCLUSIONS: KT appears
      to improve the time to failure of the extensor muscle of the trunk obtained using
      the Biering-Sorensen test. These findings suggest that KT influences processes
      that lead to muscle fatigue and that KT could be effective in the management of
      LBP.

PMID- 24284273
TI  - Ultrasound-guided steroid injection in the treatment of stump neuroma: pilot
      study.
AB  - BACKGROUND: Stump neuroma is a major cause of postamputation pain. Ultrasound is
      a practical way of imaging stump neuromas and can be employed for guiding
      therapeutic injections. OBJECTIVE: The aim of this pilot study was to investigate
      the effectiveness of ultrasound-guided steroid injection in the treatment of
      stump neuroma. METHODS: The amputee patients with stump neuroma who underwent a
      single ultrasound guided steroid injection in amputee rehabilitation unit of our
      hospital were reviewed. The pain logs employing a 11-point pain scale for each
      evaluation time (before the procedure, one day, one week, 2 weeks, 4 weeks, 6
      weeks after procedure) and a subsequent phone call approximately six months after
      procedure were used as the source of information in the study. Mean changes in
      pain levels (pain in rest and pain with prosthesis) over time were evaluated. The
      patients that had 50% decrease in pain scores were regarded as having treated
      successfully. Time after amputation and duration of pain symptom were compared
      between successfully (Group A) and unsuccessfully (Group B) treated patients.
      RESULTS: All patients (mean age, 29.7 +/- 5.5 year) in the study were male
      (n=14). 12 patients were transtibial amputee (85.7%) and 2 patients were
      transfemoral amputee (14.3%). Both mean pain scores improved significantly in
      repeated measures (pain in rest F=25.35, p< 0.01; pain with prosthesis F=81,45, p
      <0,01). A total of 7 patients (50%) were regarded as having treated successfully.
      Time after amputation and duration of pain symptom were significantly longer in
      Group B. (p< 0.05, Group A: 16.8 +/- 14.3 months after amputation, 3.5 +/- 4.1
      months pain duration; Group B: 80.2 +/- 74.2 months after amputation, 52.8 +/-
      57.6 months pain duration). CONCLUSIONS: Steroid injection may have positive
      effect in the treatment of postamputation neuroma. The patients with shorter pain
      and amputation duration may respond well to the injection.

PMID- 24284274
TI  - Influences of posterior-located center of gravity on lumbar extension strength,
      balance, and lumbar lordosis in chronic low back pain.
AB  - BACKGROUND DATA: In patients with chronic low back pain, the center of gravity
      (COG) is abnormally located posterior to the center in most cases. OBJECTIVE: The
      purpose of this study was to examine the effects of posterior-located COG on the
      functions (lumbar extension strength, and static and dynamic balance) and
      structure (lumbar lordosis angle and lumbosacral angle) of the lumbar spine.
      MATERIAL AND METHODS: In this study, the COG of chronic low back pain patients
      who complained of only low back pain were examined using dynamic body balance
      equipment. A total of 164 subjects participated in the study (74 males and 90
      females), and they were divided into two groups of 82 patients each. One group
      (n=82) consisted of patients whose COG was located at the center (C-COG); the
      other group (n=82) consisted of patients whose COG was located posterior to the
      center (P-COG). The following measures assessed the lumber functions and
      structures of the two groups: lumbar extension strength, moving speed of static
      and dynamic COGs, movement distance of the static and dynamic COGs, lumbar
      lordosis angle, and lumbosacral angle. The measured values were analyzed using
      independent t-tests. RESULTS: The group of patients with P-COG showed more
      decreases in lumbar extension strength, lumbar lordosis angle, and lumbosacral
      angle compared to the group of patients with C-COG. Also this group showed
      increases in moving speed and movement distance of the static COG. However, there
      were no differences in moving speed and movement distance of the dynamic COG
      between the two groups. CONCLUSIONS: These findings suggest that chronic LBP
      patients with P-COG have some disadvantages to establish lumbar extension
      strength and static and dynamic balance, which require specific efforts to
      maintain a neutral position and to control posture.

PMID- 24284275
TI  - Low back pain risk factors associated with persistence, recurrence and delayed
      presentation.
AB  - BACKGROUND: There is little knowledge in the literature on the role of time
      related variables for the prognosis of acute and subacute low back pain (LBP).
      OBJECTIVE: The aim of this study was to estimate the relationship between time
      related LBP characteristics and prognostic factors for acute/subacute LBP.
      METHODS: We performed a prospective inception cohort study of 315 patients
      attending a health practitioner for acute/subacute LBP or recurrent LBP. One
      tailed correlations were conducted between patient characteristics and time
      related variables. RESULTS: The pattern of correlation between risk factors for
      and resources against persistent LBP differed between three time-related
      variables. 'Subacute LBP' and 'delayed presentation' were positively associated
      with psychological factors. Both indicators were negatively correlated with
      resources against development of persistent LBP. Moreover, 'delayed presentation'
      was related positively with occupational stressors. In contrast, 'recurrent LBP'
      was only related to more impaired health-related factors. CONCLUSIONS: Patients
      with current LBP waiting longer until seeking help in primary care have a more
      disadvantageous profile of occupational and psychological risk factors and lower
      resource levels. A similar but less pronounced pattern occurred in those with
      subacute LBP compared to those with acute LBP. Consideration of time
      characteristics of LBP may help to better understand LBP.

PMID- 24284276
TI  - Relationship between isometric endurance of back extensor muscles and selected
      anthropometric indices among some Nigerian undergraduates.
AB  - BACKGROUND: Muscular endurance of the back extensors is less frequently assessed
      than muscular strength, although the endurance capabilities of these muscles may
      be as important as the strength in the prevention and treatment of low-back pain.
      OBJECTIVES: The study aimed to establish reference values, pattern of back
      extensor endurance and the relationship between isometric endurance of back
      extensor muscles and selected anthropometric indices, in apparently healthy young
      Nigerian adults. METHOD: A total of 300 young adults (150 males and 150 females)
      aged 17-30 years, participated in this Cross sectional study. The modified
      Biering-Sorensen test of Static Muscular Endurance (BSME) was used to assess
      isometric endurance of back extensor muscles. A height meter, bathroom weighing
      scale and flexible tape were used to collect data for the anthropometric indices
      Body Mass Index (BMI), Height (H), Weight (W), Waist Circumference (WC), Hip
      Circumference (HC), Waist-to-Hip Ratio (WHR), Waist-to-Height Ratio (WHtR). Data
      obtained was Summarised using descriptive statistics of frequency, percentages,
      percentile, range, mean and standard deviation, and while the Pearson Product
      Moment Correlation was used to ascertain relationship. Alpha level was set at
      0.05. RESULTS: Mean Endurance Time (ET) for all the participants was 97.56 +/-
      43.96 secs. ET was inversely related to anthropometric indices- BMI, Height,
      Weight, WC,HC, WHR, WHtR. Males had higher maximum ET than females (288 secs and
      254 secs). Gender differences was found in the anthropometric indices- BMI, WHR,
      WC, Weight and Height. Majority of the participants had medium endurance
      performance with the back endurance pattern in the ratio 1:2:1. CONCLUSION: The
      mean isometric back extensor endurance of apparently healthy young Nigerian
      adults was found to be lower than normal Biering-Sorensen holding times.

PMID- 24284277
TI  - The effectiveness of physiotherapeutic interventions in treatment of frozen
      shoulder/adhesive capsulitis: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Frozen shoulder is a common condition, yet its
      treatment remains challenging. In this review, the current best evidence for the
      use of physical therapy interventions (PTI) is evaluated. METHOD: MEDLINE,
      CINAHL, Cochrane, PEDro, ProQuest, Science Direct, and Sport Discus were searched
      for studies published in English since 2000. RESULTS: 39 articles describing the
      PTI were analyzed using Sackett's levels of evidence and were examined for
      scientific rigor. The PTI were given grades of recommendation that ranged from A
      to C. CONCLUSIONS: Therapeutic exercises and mobilization are strongly
      recommended for reducing pain, improving range of motion (ROM) and function in
      patients with stages 2 and 3 of frozen shoulder. Low-level laser therapy is
      strongly suggested for pain relief and moderately suggested for improving
      function but not recommended for improving ROM. Corticosteroid injections can be
      used for stage 1 frozen shoulder. Acupuncture with therapeutic exercises is
      moderately recommended for pain relief, improving ROM and function. Electro-
      therapy can help in providing short-term pain relief. Continuous passive motion
      is recommended for short-term pain relief but not for improving ROM or function.
      Deep heat can be used for pain relief and improving ROM. Ultrasound for pain
      relief, improving ROM or function is not recommended.

PMID- 24284278
TI  - Work-Arounds Observed by Fourth-Year Nursing Students.
AB  - Much has been written about the need for health care professionals to
      consistently promote policies and best practices that create safe, high-quality
      care environments. At times, nurses deviate from established policies and
      procedures to create work-arounds or changes in work patterns to accomplish
      patient care goals. The purpose of this study was to identify common work-arounds
      and describe what influenced the nurse to engage in the work-around as observed
      by fourth-year baccalaureate students in clinical settings. A descriptive
      qualitative approach was used to describe the findings from a Quality and Safety
      Education for Nurses-based assignment. Ninety-six individual student assignments
      were included in this analysis; the themes of infection prevention and control
      and medication management emerged. The theme of workload emerged as the reason
      why students believed nurses engaged in work-arounds. Further studies are needed
      to determine how work-arounds influence short- and long-term patient outcomes.

PMID- 24284279
TI  - In situ imaging of nano-droplet condensation and coalescence on thin water films.
AB  - Two related aspects of nano-droplet condensation and droplets coalescence are
      studied for droplets on self-supported thin water films. The experiments are
      conducted in the environmental scanning electron microscope using wet scanning
      transmission electron microscopy. Favorable condensation sites are examined and
      in-situ position-controlled condensation experiments are conducted. The
      interaction among condensed multi-droplets as well as between a single droplet
      and the underneath nano-thick water film are dynamically examined with 10nm
      lateral resolution. The droplet round shape is reshaped to flat-like facets in
      between droplets of 30-230 nm separation. Dynamic imaging of a few minutes
      duration shows a delayed coalescence effect, being explained by increased droplet
      droplet electrostatic interaction relative to van der Waals interaction. 

PMID- 24284280
TI  - A perspective on proteomics in cell biology.
AB  - During the past 15 years mass spectrometry (MS)-based analyses have become
      established as the method of choice for direct protein identification and
      measurement. Owing to the remarkable improvements in the sensitivity and
      resolution of MS instruments, this technology has revolutionised the
      opportunities available for the system-wide characterisation of proteins, with
      wide applications across virtually the whole of cell biology. In this article we
      provide a perspective on the current state of the art and discuss how the future
      of cell biology research may benefit from further developments and applications
      in the field of MS and proteomics, highlighting the major challenges ahead for
      the community in organising the effective sharing and integration of the
      resulting data mountain. 

PMID- 24284281
TI  - Subdeltoid/subacromial bursitis associated with influenza vaccination.
AB  - A 76-year-old male presented with subacromial/subdeltoid bursitis following
      influenza vaccine administration into the left deltoid muscle. This shoulder
      injury related to vaccine administration (SIRVA) could have been prevented by the
      use of a safe, evidence based protocol for the intramuscular injection of the
      deltoid muscle. 

PMID- 24284282
TI  - Co-treatment with the anti-malarial drugs mefloquine and primaquine highly
      sensitizes drug-resistant cancer cells by increasing P-gp inhibition.
AB  - The purpose of this study was to identify conditions that will increase the
      sensitivity of resistant cancer cells to anti-mitotic drugs. Currently,
      atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF),
      artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial
      drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant
      KBV20C cancer cells. None of the six tested anti-malarial drugs was found to
      better sensitize the drug-resistant cells compared to the sensitive KB cells.
      With an exception of DOY, all other anti-malarial drugs tested could sensitize
      both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs
      could be used for sensitive as well as resistant cancer cells. Furthermore, we
      examined the effects of anti-malarial drugs in combination with an antimitotic
      drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using
      viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst
      staining, we identified that two anti-malarial drugs, PRI and MEF, highly
      sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced
      sensitisation was not observed in VIN-treated sensitive KB parent cells,
      suggesting that the observed effect is specific to resistant cancer cells. We
      demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the
      inhibition of p-glycoprotein (P-gp). Our findings may contribute to the
      development of anti-malarial drug-based combination therapies for patients
      resistant to anti-mitotic drugs. 

PMID- 24284283
TI  - Site-specific growth of CdS nanostructures.
AB  - The authors report the successful site-specific deposition of cadmium sulfide
      (CdS) using a focused electron beam and a liquid-phase solution of cadmium salts
      and thiourea as the primary reagents. Nanostructures with a minimum feature size
      of 84 nm are patterned with little to no extraneous deposition. The composition
      and phase of the CdS nanostructures is investigated by energy dispersive x-ray
      spectroscopy, transmission electron microscopy and photoluminescence
      spectroscopy. Critically, these results demonstrate one-step patterning of a
      semiconducting material from a multi-reagent liquid precursor.

PMID- 24284284
TI  - Mechanisms of cadmium-induced chronotoxicity in mice.
AB  - Biological defense factors show diurnal variations in their expression levels or
      activities. These variations can induce the different sensitivity to external
      toxicants of a day. We reported earlier that mice showed clear diurnal variation
      of cadmium (Cd)-induced toxicity, i.e., chronotoxicity. In this report, we
      investigated additional new evidences for the cadmium (Cd)-induced
      chronotoxicity, and considered the mechanisms contributed to this chronotoxicity.
      Male C57BL/6J mice were injected with CdCl2 (6.4 mg/kg, one shot)
      intraperitoneally at 6 different time points of a day (zeitgeber time (ZT); ZT2,
      ZT6, ZT10, ZT14, ZT18 or ZT22) followed by monitoring the mortality until 14 days
      after the injection. We observed extreme difference in survival numbers:
      surprisingly, all mice died at ZT2 injection while all mice survived at ZT18
      injection. Moreover, in non-lethal dose of Cd (4.5 mg/kg), the values of alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) used as indexes of
      hepatotoxicity markedly increased at ZT6 injection while mostly unchanged at ZT18
      injection. To consider the mechanisms of this extreme diurnal variation, we
      examined biochemical studies and concluded that the diurnal variation was not
      caused by the differences in hepatic Cd level, basal hepatic metallothionein (MT)
      level, and induction level or induction speed of hepatic MT. We suggested that
      one of the candidate determination factors was glutathione. We believe that the
      "chronotoxicology" for metal toxicity may be classic, yet new viewpoint in modern
      toxicology field.

PMID- 24284285
TI  - Gene expression analysis using DNA microarray in HK-2 human proximal tubular
      cells treated with cadmium.
AB  - We examined the alteration of gene expression in HK-2 human proximal tubular
      cells exposed to cadmium (Cd) using DNA microarray analysis. Cd increased the
      expression of 30 genes, including 7 genes coding for heat shock proteins, more
      than 2.0-fold and decreased the expression of 21 genes, including transcription
      related genes, such as AP2B1, HOXA7, HOXA9 and TCEB2, less than 0.5-fold prior to
      the appearance of cytotoxicity in HK-2 cells. 

PMID- 24284286
TI  - Brain-specific induction of secretoglobin 3A1 expression in mice treated with
      methylmercury.
AB  - We previously analyzed gene expression in the cerebellum of mice treated with
      methylmercury using microarrays, identifying 21 different genes that increased
      expression following the administration of methylmercury. It has already been
      shown that 5 of these genes encode chemokine molecular species. Among these
      genes, the expression of CCL4 chemokine was found to be specifically induced in
      the brain following methylmercury exposure. In this study, we examined the
      remaining 16 genes showing increased brain-specific induction of expression
      following methylmercury exposure. As a result, it was shown that the gene
      expression of Scgb3a1, encoding secretoglobin 3A1, was increased specifically by
      methylmercury administration. 

PMID- 24284288
TI  - Melioidosis: refining management of a tropical time bomb.

PMID- 24284287
TI  - Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus
      doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre,
      double-blind, non-inferiority, randomised controlled trial.
AB  - BACKGROUND: Melioidosis, an infectious disease caused by the Gram-negative
      bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment
      comprises intravenous drugs for at least 10 days, followed by oral drugs for at
      least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim
      sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but
      is associated with side-effects and poor adherence by patients, and TMP-SMX alone
      is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX
      with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment.
      METHODS: For this multi-centre, double-blind, non-inferiority, randomised placebo
      controlled trial, we enrolled patients (aged >=15 years) from five centres in
      northeast Thailand with culture-confirmed melioidosis who had received a course
      of parenteral antimicrobial drugs. Using a computer-generated sequence, we
      randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus
      doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We
      followed patients up every 4 months for 1 year and annually thereafter to the end
      of the study. The primary endpoint was culture-confirmed recurrent melioidosis,
      and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is
      registered with www.controlled-trials.com, number ISRCTN86140460. FINDINGS: We
      enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315
      to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group
      and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture
      confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for
      non-inferiority was met (p=0.01). Adverse drug reactions were less common in the
      TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%]
      vs 167 [53%]). INTERPRETATION: Our findings suggest that TMP-SMX is not inferior
      to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is
      preferable on the basis of safety and tolerance by patients. FUNDING: Thailand
      Research Fund, the Melioidosis Research Center, the Center of Excellence in
      Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome
      Trust.

PMID- 24284289
TI  - Leflunomide-induced interstitial lung disease (a systematic review).
AB  - BACKGROUND: Leflunomide, a disease modifying anti-rheumatic drug in use since
      1998, causes interstitial lung disease (ILD) and other pulmonary complications.
      METHODS: We undertook a systematic review of literature of PubMed (March 2013) to
      identify the published literature pertaining to pulmonary toxicity associated
      with leflunomide. RESULTS: We identified 41 relevant articles detailing four
      population studies and case reports/series on an additional 42 patients.
      Available data were reviewed and summarized. CONCLUSIONS: Leflunomide can cause
      ILD. Most of these patients present within three months of starting leflunomide
      with acute symptoms for a week or less. Bilateral ground glass opacities and
      diffuse alveolar damage are the most common radiologic and histopathologic
      findings, respectively. Patients with pre-existing ILD are particularly at risk
      for this complication, and leflunomide should be avoided in this population.
      Activated charcoal and cholestyramine significantly decrease the half-life of the
      drug because of its enterohepatic circulation and should be considered in cases
      with acute toxicity.

PMID- 24284290
TI  - Human embryonic stem cells recover in vivo acute lung inflammation bleomycin
      induced.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by alveolar epithelial cell
      injury, type II cell activation, apoptosis and bronchiolar epithelial cell
      proliferation, accumulation of extracellular matrix and fibroblasts. No current
      animal model recapitulates all of these cardinal manifestation of the human
      disease. However, bleomycin instillation in mice lung by intranasal way (ITN)
      represents the best experimental model of pulmonary fibrosis in which alveolar
      pneumocytes type II (ATII) are usually depleted. The aim of this study was to
      test the possibility to recover acute lung fibrosis after transplantation of
      human embryonic type II derived-pneumocytes in a murine model of bleomycin
      induced damage. Our results indicate the striking "clinical" beneficial effect of
      differentiated HUES-3 cells into ATII in terms of lung function, weight loss and
      mortality in injured mice, suggesting this stem cell therapy as a promising,
      systemic and specific treatment of human pulmonary fibrosis.

PMID- 24284291
TI  - Socio-demographic profile of patients with sarcoidosis vis-a-vis tuberculosis.
AB  - BACKGROUND: Sarcoidosis and tuberculosis closely resemble each other and
      Mycobacterium tuberculosis has been implicated as a causative agent for
      sarcoidosis. Herein we explore the socio-demographic features of patients with
      sarcoidosis vis-a-vis tuberculosis. METHODOLOGY: In a prospective case-control
      design, we studied hundred patients each of newly diagnosed sarcoidosis,
      bacteriologically confirmed pulmonary tuberculosis and healthy controls. Socio
      demographic profile was recorded on a standardized questionnaire. Information
      about tobacco smoking, exposure to environmental tobacco smoke (ETS) and cooking
      fuels was also collected. Various parameters were compared among the three
      groups. RESULTS: Compared to tuberculosis, patients with sarcoidosis were elder,
      had better body mass index (BMI), higher urban residence (OR 2.19, 95% CI: 1.02
      4.69), were better educated (ORs 8.50 to 74.25 for different categories), had
      higher per capita income (OR 13.33; 95% CI: 6.79-26.19) and belonged to better
      overall socio-economic status (SES) (ORs 8.57-195.0 for different categories).
      All these differences were also significant when sarcoidosis patients were
      compared to healthy controls albeit to a lesser degree. Tobacco smoking, ETS
      exposure and use of fossil/biomass fuels for cooking were more commonly seen in
      TB patients. In the multivariate analysis, as compared to TB or controls,
      sarcoidosis patients had higher odds for a better SES after adjusting for age,
      gender, BMI, religion, smoking, ETS exposure and cooking fuel. CONCLUSIONS:
      Patients with sarcoidosis are likely to be better educated and more affluent
      compared to those with tuberculosis and healthy controls and this can be useful
      in clinical differential diagnosis of the two conditions in populations with high
      prevalence of TB.

PMID- 24284292
TI  - Oncostatin M in bronchoalveolar lavage correlates with the severity of
      sarcoidosis.
AB  - BACKGROUND: Recent studies have shown that oncostatin M (OSM) might have a role
      in T cell-mediated inflammatory processes in which mast cells are also involved.
      Patients with severe sarcoidosis might develop fibrotic changes in the lung. We
      assessed whether there was a correlation between mast cells expressing OSM in
      bronchoalveolar lavage (BAL) and the severity of sarcoidosis. PATIENTS AND
      METHODS: Twelve consecutive patients with new diagnosis of sarcoidosis were
      eligible for the study. All underwent complete lung function tests, angiotensin
      converting enzyme (ACE), and bronchoscopy that included BAL and biopsies.
      Cytospins of BAL were prepared. All samples were incubated with the primary
      antibody rabbit anti-human c-kit, CD117 and stained for total mast cell count.
      The mouse anti-human Oncostatin M was applied and activated mast cells were
      counted. Clinical sarcoidosis parameters including ACE and lung functions were
      correlated with mast cells in BAL, as well as with OSM positive mast cells.
      RESULTS: FEV1 % was correlated with the percentage of activated mast cells, as
      well as with the percentage of OSM positive mast cells (r=0.61, p=0.033, 95% CI:
      0.06-0.87; r=0.58, p=0.04, 95% CI: 0.015-0.86, respectively). FVC and FEV1/FVC
      correlated with activated mast cells (r=0.58, p=0.05; r=0.63, p=0.028,
      respectively). CONCLUSIONS: Direct correlation was found between clinical
      parameters including lung function tests (FEV1 and FVC) and OSM secretion from
      mast cells in patients with sarcoidosis. These findings suggest that mast cells
      and OSM have a role in sarcoidosis. Further studies to confirm these preliminary
      results are suggested.

PMID- 24284294
TI  - Association of sarcoidosis and ulcerative colitis: a review of 20 cases.
AB  - Sarcoidosis and ulcerative colitis is a rare association. We report a case of
      this association and describe its clinical, radiological and functional
      characteristics based on a review of the literature. This association must be
      recognized by the physician and must be clearly distinguished from a systemic
      site of ulcerative colitis or drug-related pneumonitis. 

PMID- 24284293
TI  - Effects of broad-spectrum antimycobacterial therapy on chronic pulmonary
      sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is an idiopathic, granulomatous disease for which
      molecular and immunologic studies have shown an association between it and
      mycobacterial antigens. Microbial antigens can reduce expression of the tyrosine
      kinase Lck, which has been associated with sarcoidosis severity. Here we
      investigate the efficacy of Concomitant Levofloxacin, Ethambutol, Azithromycin,
      and Rifampin (the CLEAR regimen) for treatment of chronic, pulmonary sarcoidosis.
      METHODS: Fifteen chronic, pulmonary sarcoidosis patients with forced vital
      capacities (FVC) between 45-80% of predicted were enrolled in this open-label
      trial. The primary efficacy endpoint was change in absolute FVC from baseline to
      completion of therapy. Secondary endpoints were change in functional capacity
      measured by Six Minute Walk Distance (6MWD) and quality of life assessment
      measured by St. George's Respiratory Questionnaire (SGRQ). RESULTS: Of 15
      patients enrolled, 11 completed 4 weeks of therapy, and 8 completed 8 weeks of
      therapy. The CLEAR regimen was associated with an increase in FVC of 0.23 liters
      at 4 weeks and 0.42 liters at 8 weeks (P=0.0098 and 0.016, respectively). The
      6MWD increased by 87 meters from baseline to 8 weeks (p=0.0078). The mean score
      of the validated SGRQ was improved at 8 weeks over baseline (p=0.023). Normalized
      expression of Lck and NF-kappaB was observed in those with clinical improvement.
      CONCLUSIONS: The CLEAR regimen is associated with improved absolute FVC, as well
      as increased functional capacity and quality-of-life in selected chronic
      pulmonary sarcoidosis patients. Larger, randomized, controlled trials are needed
      to confirm these findings and to identify patients most likely to benefit from
      therapy. ClinicalTrials.gov number NCT01169038.

PMID- 24284295
TI  - Hermansky Pudlak Syndrome and Pulmonary Alveolar Proteinosis at the same patient:
      first case report in the world literature.
AB  - Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disorder presenting
      with oculocutaneous albinism, bleeding diathesis and lysosomal accumulation of
      ceroid lipofuscin which leads to interstitial fibrosis in lung. Pulmonary
      fibrosis which is usually associated with HPS-1 and HPS-4 subtypes usually
      manifests in the third/fourth decades of life representing with giant lamellar
      bodies of alveolar type-II-cells and their apparent degeneration causes
      restrictive lung disease. Pulmonary manifestation of this syndrome may lead to
      premature death. Pulmonary Alveolar Proteinosis(PAP) is another rare disease
      characterized by alveolar deposition of surfactant phospholipids and proteins
      secondary to defective clearance by alveolar macrophages. PAP may occur as
      autoimmune diseases and/or secondary to toxic inhalation, systemic infections or
      hematological disorders. None of the cases were reported secondary to HPS
      according to the best our knowledge. As well, pulmonary involvement of HPS was
      never reported as PAP. We report the first case of PAP in a patient with HPS. 

PMID- 24284296
TI  - A Novel Missense Mutation of DKC1 In Dyskeratosis Congenita With Pulmonary
      Fibrosis.
AB  - Dyskeratosis congenita (DC) is a rare inherited multisystem disorder caused by
      mutations in seven genes involved in telomere biology, with approximately 20% of
      cases having pulmonary complications. DKC1 mutations exhibit a severe disease
      phenotype of DC that develops in early childhood. Here, we report a unique case
      of DC with pulmonary fibrosis diagnosed at the age of 46. A novel missense
      mutation(p.Arg65Lys) of DKC1 was detected, and predicted to show a weak mutagenic
      effect. In spite of the steroid and immunosuppressive treatment, he died of an
      acute exacerbation seven months after the initial visit. This case suggests that
      mutation subtypes can cause heterogeneity in DC and pulmonary fibrosis.

PMID- 24284297
TI  - Sulfasalazine induced lung toxicity masquerading as sarcoidosis--case report and
      review of the literature.
AB  - A commonly prescribed drug for Rheumatoid Arthritis (R.A) and Inflammatory Bowel
      Disease (IBD) treatment, Sulfasalazine can occasionally cause lung toxicity such
      as interstitial pneumonitis and eosinophilic pneumonias. We report a case of a 46
      year old female being treated with Sulfasalazine for Ulcerative Colitis, who
      developed shortness of breath and a radiographic pattern of hilar adenopathy.
      Biopsy showed granulomas that resembled Sarcoidosis. We review different
      presentations of Sulfasalazine induced lung disease and describe the first known
      case of Sulfasalazine lung toxicity mimicking Sarcoidosis. 

PMID- 24284298
TI  - Chronic bronchiolitis in ankylosing spondylitis.
AB  - The pleuro-pulmonary signs of ankylosing spondylitis are generally asymptomatic,
      typically represented by biapical lung fibrosis. To our knowledge, the severe
      bronchiolitis which is sometimes observed in other spondyloarthropathies has not
      been described in ankylosing spondylitis. We report two cases of severe chronic
      bronchiolitis in ankylosing spondylitis patients. Their clinical and radiological
      presentation were similar, characterized by progressive deterioration of stage
      III-IV dyspnea, non-reversible obstructive ventilatory defect, and CT scan
      showing air trapping with mosaic attenuation and ground-glass opacity in
      expiration. Lung biopsies confirmed the diagnosis of severe follicular
      bronchiolitis in one patient and constrictive bronchiolitis is suspected in the
      other. Only the patient with follicular bronchiolitis responded positively to
      treatment with low doses of macrolides. 

PMID- 24284299
TI  - Cardiac sarcoidosis and coronary artery disease: a two-hit mechanism to left
      ventricular dysfunction (or is it)?
AB  - This report describes a case of cardiac sarcoidosis in a 40-year-old man with
      minimal risk factors for coronary artery disease who was found to have a critical
      coronary lesion on angiography performed for declining left ventricular function.
      The case highlights the diagnostic and therapeutic issues surrounding cardiac
      sarcoidosis and raises the question of a possible link between sarcoidosis and
      premature coronary artery disease. It also stresses the importance of ruling out
      ischemia in any patient with declining left ventricular function. 

PMID- 24284300
TI  - Seasonality of sarcoidosis: the 'heat' is on....

PMID- 24284301
TI  - Om Prakash Sharma, MD, FRCP, FCCP. 4 July 1936-19 August 2012. Internationally
      acclaimed specialist in sarcoidosis.

PMID- 24284302
TI  - Effect of single layer centrifugation using Androcoll-E-Large on the sperm
      quality parameters of cooled-stored donkey semen doses.
AB  - The aim of this study was to determine the effect of single layer centrifugation
      (SLC) using Androcoll-E-Large on donkey sperm quality parameters after 24 h of
      cool-storage. Ejaculates were collected from Andalusian donkeys and then cooled
      at 5 degrees C. SLC was carried out after 24 h of cool-storage using Androcoll-E
      Large. In the first experiment, all sperm parameters assessed (total and
      progressive sperm motility, viability, sperm morphology and sperm kinematics VCL,
      VSL, VAP, LIN, STR, WOB, ALH and BCF) were statistically compared between semen
      samples processed or not with Androcoll-E-Large. Significant differences (P<0.05)
      were found between SLC-selected and unselected semen samples for all parameters
      assessed, obtaining better results after SLC. In the second experiment, semen
      samples were classified in two groups according to their sperm progressive
      motility (PM) before SLC. Then, the increments obtained in semen quality
      parameters after SLC were compared between groups. No significant differences
      were found between groups, indicating that SLC improved the sperm quality
      parameters of entire set of semen samples processed with independence to their
      original PM. In conclusion, SLC with Androcoll-E-Large can be used in donkeys,
      increasing the sperm quality of cooled-stored donkey semen doses after 24 h of
      cool storage.

PMID- 24284303
TI  - Production and characterization of murine monoclonal antibody against synthetic
      peptide of CD34.
AB  - BACKGROUND: The treatment of hematologic malignancies and immunodeficiency
      diseases are offered by hematopoietic stem cells (HSCs) as a unique self-renewal
      and differentiation source which most commonly is selected by CD34 surface marker
      for HSC. OBJECTIVE: The purpose of this study was to develop and characterize
      monoclonal antibody against CD34 antigen for detection of hematopoietic stem
      cells. METHODS: Balb/c mice were immunized with two synthetic peptides of CD34
      and Spleen cells were fused with SP2/0.Fused cells were grown in hypoxanthine,
      aminopterine and thymidine (HAT) selective medium and cloned by limiting
      dilution. Large scale of monoclonal antibodies was produced by mouse ascites
      production of mAb (in vivo) method. Monoclonal antibody was purified by
      chromatography. Then reactivity of these antibodies was evaluated in different
      immunological assays including ELISA, immunofluorescence (IF), western blot (WB)
      and flowcytometry. RESULTS: In this study, between five positive clone wells, two
      clones were chosen for limiting dilution. Limiting dilution product was one
      monoclone (3-D5 monoclone) with absorbance about 2. Isotype of this mAb was
      identified as IgG1 class with Kappa (kappa) light chain. CONCLUSIONS: This
      antibody is highly specific and functional in biomedical applications such as
      ELISA, flowcytometry, immunofluorescence, and western blot assays.

PMID- 24284304
TI  - Future prospects of monoclonal antibodies as magic bullets in immunotherapy.
AB  - Monoclonal antibody therapy has become a critical component of clinical treatment
      procedure for a variety of indications. Therapeutic antibodies have made the
      transition from conception to clinical reality over the past two decades. Now,
      many of mAbs are being tested as adjuvant or first-line therapies to determine
      their efficacy in improving survival. In the future, the information drawn from
      genomemedical science and genome-informatics, that list the disease-related
      antigens useful for medical treatment, should be essential to develop the therapy
      using mAbs. Currently, the more attention is getting paid toward monoclonal
      antibody therapy. Several monoclonal antibodies, alone and in combination with
      other conventional therapies, are being tested in phase I and phase II clinical
      trials at the moment. Monoclonal antibody therapy can be done by using antibody
      fragments, antibody fusions with effector proteins and intrabodies. The large
      size and the long half-life of full-length antibody make them an inappropriate
      tool for radioimmunotherapy. Therefore, scientists produced some antibody
      fragments including scFv, Diabody and Nanobodies (sdAbs) which have smaller size
      besides maintaining the binding activity of the full-length molecule. Immunotoxin
      and Immunocytokines are consisting of toxin and cytokines fused to antibody
      fragments. An intrabody is produced by entering antibody into the cell and act
      against intracellular compartments. 

PMID- 24284305
TI  - Tumor angiogenesis and anti-angiogenic therapies.
AB  - Angiogenesis, the development and growth of blood vessels, is a major topic of
      research which began in 1971 with Folkman's original hypothesis. Different
      mechanisms of blood vessel growth are sprouting and intussusceptive angiogenesis,
      vascular mimicry, and blood vessel cooption. Dis-regulated angiogenesis may
      result in numerous angiogenic diseases and is responsible for solid tumor growth
      and metastasis. Vascular endothelial cells are generally dormant in adult but in
      pathological conditions when tumors reach a size of about 0.2-2.0 mm in diameter,
      they become hypoxic and hindered in tumor growth in the lack of angiogenesis.
      During angiogenic switch pro-angiogenic factors predominate and result in
      angiogenesis and tumor progression. Angiogenesis switch leads to the increased
      production of vascular endothelial growth factor (VEGF) following up-regulation
      of the hypoxia-inducible transcription factor. The VEGF family comprises from
      VEGF (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). The
      VEGF family of receptors consists of three protein-tyrosine kinases. Now, the
      most conventional approach for controlling tumor angiogenesis is blockade of the
      vascular endothelial growth factor (VEGF) pathway. The results of preclinical
      studies, substantial therapeutic effects of VEGF blockers have been stated in
      various types of human cancers, even in progressive or recurrent cancer cases. 

PMID- 24284306
TI  - Developing and mature human granulocytes express ELP 6 in the cytoplasm.
AB  - BACKGROUND: c3orf75 is a conserved open reading frame within the human genome and
      has recently been identified as the Elongator subunit, ELP6 [1]. The Elongator
      enzyme complex has diverse roles, including translational control, neuronal
      development, cell migration and tumorigenicity [2]. OBJECTIVE: To identify genes
      expressed early in human eosinophil development. METHODS: Eosinophilopoiesis was
      investigated by gene profiling of IL-5 stimulated CD34+ cells; ELP6 mRNA is
      upregulated. A monoclonal antibody was raised to the recombinant protein
      predicted by the open reading frame. RESULTS: ELP6 transcripts are upregulated in
      a human tissue culture model of eosinophil development during gene profiling
      experiments. Transcripts are expressed in most tissue types, as shown by reverse
      transcriptase PCR. Western blot experiments show that human ELP6 is a 30 kDa
      protein expressed in the bone marrow, as well as in many other tissues. Flow
      cytometry experiments of human bone marrow mononuclear cells show that ELP6 is
      expressed intracellularly, in developing and mature human neutrophils,
      eosinophils and monocytes. CONCLUSIONS: ELP6 is expressed intracellularly in
      developing and mature granulocytes and monocytes but not in lymphocytes and
      erythrocytes.

PMID- 24284307
TI  - Presence of aberrant VH6 domains in anti-interferon-gamma autoantibodies in
      multiple sclerosis.
AB  - BACKGROUND: Anti-cytokine autoantibodies (auto-Abs) are ubiquitous both in
      patients suffering from infectious, inflammatory and autoimmune diseases and in
      healthy individuals. Particularly anti-IFN-gamma auto-Abs are shown to be
      elevated in blood of multiple sclerosis (MS) patients. OBJECTIVE: The aim of
      present study was to investigate whether repertoires of anti-IFN-gamma auto-Abs
      differ in MS patients and healthy donors. METHODS: Using phage display technique
      we have compared repertoires of the genes encoding anti-IFN-gamma single-chain
      variable fragments selected from MS and naive phage display libraries. RESULTS:
      The panel of anti-IFN-gamma auto-Abs selected from MS library includes (i)
      'fetal' auto-Abs, encoded by the VH6-1 gene segment and the combination proximal
      D segments with distal JH segments; (ii) naive auto-Abs; (iii) affinity maturated
      antibodies; and (iv) abnormal single-domain antibodies. Meanwhile, the panel of
      anti-IFN-gamma auto-Abs selected from naive library mainly contains the naive
      antibodies. Moreover, the overall antibody repertoire of MS library is skewed
      compared to the overall repertoire of naive library and also contained the
      antibodies carrying a 'fetal' VH6 domain and the ratio of kappa and lambda chains
      was reversed. CONCLUSIONS: These results suggest existence of a special mechanism
      or trigger that provides for reconstitution of the immune system in MS.

PMID- 24284308
TI  - Sensitive antibody-based CTCs detection from peripheral blood.
AB  - The detection of Circulating Tumor Cells (CTC) is a purpose in numerous oncology
      research fields. CTCs are disseminated from the original site from metastatic and
      primary tumors in the peripheral blood of breast, prostate, lung and colorectal
      cancer patients. Different characteristics of tumor cells have been applied to
      define enrichment methods through the differential expression of tumor-specific
      markers on the surface of the cells. Antibody-based affinity methods can provide
      the separation of CTCs via the expression of specific antigens on the surface of
      epithelial tumor cells or hematopoietic cells. Developments in CTC detection
      methods will improve a wide range of clinical applications, as well as the
      discovery of biomarkers to predict treatment responses and disease progression.
      In this mini-review, different CTCs detection approaches base on antibodies for
      enrichment of circulating tumor cells will be discussed and elucidated the
      methods for CTCs detection biomarkers on the current knowledge. 

PMID- 24284309
TI  - Comparison of the Surgical Pleth Index with autonomic nervous system modulation
      on cardiac activity during general anaesthesia: A randomised cross-over study.
AB  - BACKGROUND: Surgical plethysmographic index (SPI) has been proposed as a tool to
      measure the nociception/antinociception balance during general anaesthesia.
      Untreated nociception may increase sympathetic tone, but the relationship between
      SPI and the autonomic nervous system (ANS) is poorly understood. OBJECTIVE: We
      hypothesised that two different levels of SPI might be associated with
      differences in ANS modulation, measured by the frequency domain analysis of heart
      rate variability (HRV). DESIGN: A randomised, cross-over group study, conducted
      between February and November 2009. SETTING: University tertiary referral
      hospital in Milan, Italy. PATIENTS: Forty-two adult patients undergoing scheduled
      laparoscopic abdominal surgery. INTERVENTIONS: ECG, noninvasive arterial blood
      pressure and SPI were recorded during balanced general anaesthesia with inhaled
      sevoflurane and intravenous remifentanil. After pneumoperitoneum induction, the
      remifentanil infusion rate was set to obtain two different levels of SPI (>50, HI
      SPI, and <50, LO-SPI) for each patient. MAIN OUTCOME MEASURES: Arterial pressure,
      heart rate (HR), low-frequency and high-frequency spectral components, the low
      frequency/high frequency ratio (measure of sympathovagal balance) and whole power
      spectrum density of HRV were measured at the two different levels of SPI.
      RESULTS: Thirty-nine patients were included in the final analysis. During LO-SPI,
      HR and systolic and mean blood pressures were significantly lower than HI-SPI.
      The median low frequency/high frequency ratio was reduced during LO-SPI [1.29
      interquartile range (IQR) 0.66 to 2.05) vs. 2.36 (1.30 to 3.62), P = 0.008]. The
      sensitivity analysis revealed a significant correlation between SPI changes and
      changes of all ANS indices, arterial pressure and HR, with a slightly better
      correlation for low frequency/high frequency (Spearman rho = 0.70, IQR 0.484 to
      0.834, P < 0.001). CONCLUSION: In the context of a balanced general anaesthesia
      in healthy patients undergoing laparoscopic abdominal surgery, ANS modulation
      seems to correlate with changes in SPI. Further studies are warranted to assess
      whether this may reflect a change in nociception/antinociception balance or a
      pharmacodynamic effect of remifentanil.

PMID- 24284310
TI  - The role of bacterial phytotoxins in inhibiting the eukaryotic proteasome.
AB  - The ubiquitin-26S proteasome degradation system (UPS) plays a pivotal role in
      almost all aspects of plant life, including defending against pathogens. Although
      the proteasome is important for plant immunity, it has been found to be also
      exploited by pathogens using effectors to increase their virulence. Recent work
      on the XopJ effector and syringolin A/syrbactins has highlighted host proteasome
      inhibition as a virulence strategy of pathogens. This review will focus on these
      recent developments. 

PMID- 24284311
TI  - The risk of low-to-moderate prenatal alcohol exposure on child academic
      underachievement and behaviour may be difficult to measure and should not be
      underestimated.

PMID- 24284312
TI  - Treating mild gestational diabetes yields benefits with little or no evidence of
      harms.

PMID- 24284313
TI  - Seven days of non-invasive cardiac monitoring early postischaemic stroke or TIA
      increases atrial fibrillation detection rate compared with current guideline
      based practice.

PMID- 24284314
TI  - A bromodomain-containing host protein mediates the nuclear importation of a
      satellite RNA of Cucumber mosaic virus.
AB  - Replication of the satellite RNA (satRNA) of Cucumber Mosaic Virus is dependent
      on replicase proteins of helper virus (HV). However, we recently demonstrated
      that like with Potato spindle tuber viroid (PSTVd), a satRNA associated with
      Cucumber Mosaic Virus strain Q (Q-satRNA) has the propensity to localize in the
      nucleus and generate multimers that subsequently serve as templates for HV
      dependent replication. But the mechanism regulating the nuclear importation of Q
      satRNA is unknown. Here we show that the nuclear importation of Q-satRNA is
      mediated by a bromodomain-containing host protein (BRP1), which is also
      apparently involved in the nuclear localization of PSTVd. A comparative analysis
      of nuclear and cytoplasmic fractions from Nicotiana benthamiana plants coinfected
      with Q-satRNA and its HV confirmed the association of Q-satRNA but not HV with
      the nuclear compartment. A combination of the MS2-capsid protein-based RNA
      tagging assay and confocal microscopy demonstrated that the nuclear localization
      of Q-satRNA was completely blocked in transgenic lines of Nicotiana benthamiana
      (ph5.2nb) that are defective in BRP1 expression. This defect, however, was
      restored when the ph5.2nb lines of N. benthamiana were trans-complemented by
      ectopically expressed BRP1. The binding specificity of BRP1 with Q-satRNA was
      confirmed in vivo and in vitro by coimmunoprecipitation and electrophoretic
      mobility shift assays, respectively. Finally, infectivity assays involving
      coexpression of Q-satRNA and its HV in wild-type and ph5.2nb lines of N.
      benthamiana accentuated a biological role for BRP1 in the Q-satRNA infection
      cycle. The significance of these results in relation to a possible evolutionary
      relationship to viroids is discussed. 

PMID- 24284315
TI  - Mutations in the N terminus of the oX174 DNA pilot protein H confer defects in
      both assembly and host cell attachment.
AB  - The oX174 DNA pilot protein H forms an oligomeric DNA-translocating tube during
      penetration. However, monomers are incorporated into 12 pentameric assembly
      intermediates, which become the capsid's icosahedral vertices. The protein's N
      terminus, a predicted transmembrane helix, is not represented in the crystal
      structure. To investigate its functions, a series of absolute and conditional
      lethal mutations were generated. The absolute lethal proteins, a deletion and a
      triple substitution, were efficiently incorporated into virus-like particles
      lacking infectivity. The conditional lethal mutants, bearing cold-sensitive (cs)
      and temperature-sensitive (ts) point mutations, were more amenable to further
      analyses. Viable particles containing the mutant protein can be generated at the
      permissive temperature and subsequently analyzed at the restrictive temperature.
      The characterized cs defect directly affected host cell attachment. In contrast,
      ts defects were manifested during morphogenesis. Particles synthesized at
      permissive temperature were indistinguishable from wild-type particles in their
      ability to recognize host cells and deliver DNA. One mutation conferred an
      atypical ts synthesis phenotype. Although the mutant protein was efficiently
      incorporated into virus-like particles at elevated temperature, the progeny
      appeared to be kinetically trapped in a temperature-independent, uninfectious
      state. Thus, substitutions in the N terminus can lead to H protein
      misincorporation, albeit at wild-type levels, and subsequently affect particle
      function. All mutants exhibited recessive phenotypes, i.e., rescued by the
      presence of the wild-type H protein. Thus, mixed H protein oligomers are
      functional during DNA delivery. Recessive and dominant phenotypes may temporally
      approximate H protein functions, occurring before or after oligomerization has
      gone to completion. 

PMID- 24284316
TI  - Palmitoylation and p8-mediated human T-cell leukemia virus type 1 transmission.
AB  - The orf-I gene of human T-cell leukemia type 1 (HTLV-1) encodes p8 and p12 and
      has a conserved cysteine at position 39. p8 and p12 form disulfide-linked dimers,
      and only the monomeric forms of p8 and p12 are palmitoylated. Mutation of
      cysteine 39 to alanine (C39A) abrogated dimerization and palmitoylation of both
      proteins. However, the ability of p8 to localize to the cell surface and to
      increase cell adhesion and viral transmission was not affected by the C39A
      mutation. 

PMID- 24284317
TI  - Genetic resistance to scrapie infection in experimentally challenged goats.
AB  - In goats, several field studies have identified coding mutations of the gene
      encoding the prion protein (I/M142, N/D146, S/D146, R/Q211, and Q/K222) that are
      associated with a lower risk of developing classical scrapie. However, the data
      related to the levels of resistance to transmissible spongiform encephalopathies
      (TSEs) of these different PRNP gene mutations are still considered insufficient
      for developing large-scale genetic selection against scrapie in this species. In
      this study, we inoculated wild-type (WT) PRNP (I142R154R211Q222) goats and
      homozygous and/or heterozygous I/M142, R/H154, R/Q211, and Q/K222 goats with a
      goat natural scrapie isolate by either the oral or the intracerebral (i.c.)
      route. Our results indicate that the I/M142 PRNP polymorphism does not provide
      substantial resistance to scrapie infection following intracerebral or oral
      inoculation. They also demonstrate that H154, Q211, and K222 PRNP allele carriers
      are all resistant to scrapie infection following oral exposure. However, in
      comparison to WT animals, the H154 and Q211 allele carriers displayed only
      moderate increases in the incubation period following i.c. challenge. After i.c.
      challenge, heterozygous K222 and a small proportion of homozygous K222 goats also
      developed the disease, but with incubation periods that were 4 to 5 times longer
      than those in WT animals. These results support the contention that the K222 goat
      prion protein variant provides a strong but not absolutely protective effect
      against classical scrapie. 

PMID- 24284319
TI  - In vivo electroporation of minicircle DNA as a novel method of vaccine delivery
      to enhance HIV-1-specific immune responses.
AB  - DNA vaccines offer advantage over conventional vaccines, as they are safer to
      use, easier to produce, and able to induce humoral as well cellular immune
      responses. Unfortunately, no DNA vaccines have been licensed for human use for
      the difficulties in developing an efficient and safe in vivo gene delivery
      system. In vivo electroporation (EP)-based DNA delivery has attracted great
      attention for its potency to enhance cellular uptake of DNA vaccines and function
      as an adjuvant. Minicircle DNA (a new form of DNA containing only a gene
      expression cassette and lacking a backbone of bacterial plasmid DNA) is a
      powerful candidate of gene delivery in terms of improving the levels and the
      duration of transgene expression in vivo. In this study, as a novel vaccine
      delivery system, we combined in vivo EP and the minicircle DNA carrying a codon
      optimized HIV-1 gag gene (minicircle-gag) to evaluate the immunogenicity of this
      system. We found that minicircle-gag conferred persistent and high levels of gag
      expression in vitro and in vivo. The use of EP delivery further increased
      minicircle-based gene expression. Moreover, when delivered by EP, minicircle-gag
      vaccination elicited a 2- to 3-fold increase in cellular immune response and a
      1.5- to 3-fold augmentation of humoral immune responses compared with those
      elicited by a pVAX1-gag positive control. Increased immunogenicity of EP-assisted
      minicircle-gag may benefit from increasing local antigen expression, upregulating
      inflammatory genes, and recruiting immune cells. Collectively, in vivo EP of
      minicircle DNA functions as a novel vaccine platform that can enhance efficacy
      and immunogenicity of DNA vaccines. 

PMID- 24284318
TI  - Antigenic properties of the HIV envelope on virions in solution.
AB  - The structural flexibility found in human immunodeficiency virus (HIV) envelope
      glycoproteins creates a complex relationship between antigenicity and sensitivity
      to antiviral antibodies. The study of this issue in the context of viral
      particles is particularly problematic as conventional virus capture approaches
      can perturb antigenicity profiles. Here, we employed a unique analytical system
      based on fluorescence correlation spectroscopy (FCS), which measures antibody
      virion binding with all reactants continuously in solution. Panels of nine anti
      envelope monoclonal antibodies (MAbs) and five virus types were used to connect
      antibody binding profiles with neutralizing activities. Anti-gp120 MAbs against
      the 2G12 or b12 epitope, which marks functional envelope structures, neutralized
      viruses expressing CCR5-tropic envelopes and exhibited efficient virion binding
      in solution. MAbs against CD4-induced (CD4i) epitopes considered hidden on
      functional envelope structures poorly bound these viruses and were not
      neutralizing. Anti-gp41 MAb 2F5 was neutralizing despite limited virion binding.
      Similar antigenicity patterns occurred on CXCR4-tropic viruses, except that anti
      CD4i MAbs 17b and 19e were neutralizing despite little or no virion binding.
      Notably, anti-gp120 MAb PG9 and anti-gp41 MAb F240 bound to both CCR5-tropic and
      CXCR4-tropic viruses without exerting neutralizing activity. Differences in the
      virus production system altered the binding efficiencies of some antibodies but
      did not enhance antigenicity of aberrant gp120 structures. Of all viruses tested,
      only JRFL pseudoviruses showed a direct relationship between MAb binding
      efficiency and neutralizing potency. Collectively, these data indicate that the
      antigenic profiles of free HIV particles generally favor the exposure of
      functional over aberrant gp120 structures. However, the efficiency of virion
      antibody interactions in solution inconsistently predicts neutralizing activity
      in vitro. 

PMID- 24284320
TI  - The rigid amphipathic fusion inhibitor dUY11 acts through photosensitization of
      viruses.
AB  - Rigid amphipathic fusion inhibitors (RAFIs) are lipophilic inverted-cone-shaped
      molecules thought to antagonize the membrane curvature transitions that occur
      during virus-cell fusion and are broad-spectrum antivirals against enveloped
      viruses (Broad-SAVE). Here, we show that RAFIs act like membrane-binding
      photosensitizers: their antiviral effect is dependent on light and the generation
      of singlet oxygen ((1)O(2)), similar to the mechanistic paradigm established for
      LJ001, a chemically unrelated class of Broad-SAVE. Photosensitization of viral
      membranes is a common mechanism that underlies these Broad-SAVE.

PMID- 24284321
TI  - Cellular vimentin regulates construction of dengue virus replication complexes
      through interaction with NS4A protein.
AB  - Dengue virus (DENV) interacts with host cellular factors to construct a more
      favorable environment for replication, and the interplay between DENV and the
      host cellular cytoskeleton may represent one of the potential antiviral targeting
      sites. However, the involvement of cellular vimentin intermediate filaments in
      DENV replication has been explored less. Here, we revealed the direct interaction
      between host cellular vimentin and DENV nonstructural protein 4A (NS4A), a known
      component of the viral replication complex (RC), during DENV infection using
      tandem affinity purification, coimmunoprecipitation, and scanning electron
      microscopy. Furthermore, the dynamics of vimentin-NS4A interaction were
      demonstrated by using confocal three-dimensional (3D) reconstruction and
      proximity ligation assay. Most importantly, we report for the first time the
      discovery of the specific region of NS4A that interacts with vimentin lies within
      the first 50 amino acid residues at the cytosolic N-terminal domain of NS4A (N50
      region). Besides identifying vimentin-NS4A interaction, vimentin reorganization
      and phosphorylation by calcium calmodulin-dependent protein kinase II occurs
      during DENV infection, signifying that vimentin reorganization is important in
      maintaining and supporting the DENV RCs. Interestingly, we found that gene
      silencing of vimentin by small interfering RNA induced a significant alteration
      in the distribution of RCs in DENV-infected cells. This finding further supports
      the crucial role of intact vimentin scaffold in localizing and concentrating DENV
      RCs at the perinuclear site, thus facilitating efficient viral RNA replication.
      Collectively, our findings implicate the biological and functional significance
      of vimentin during DENV replication, as we propose that the association of DENV
      RCs with vimentin is mediated by DENV NS4A. 

PMID- 24284322
TI  - Nucleophosmin contributes to the transcriptional activation function of the
      Epstein-Barr virus EBNA1 protein.
AB  - The Epstein-Barr virus (EBV) EBNA1 protein plays important roles in latent
      infection, including transcriptional activation of EBV latency genes by binding
      to the family-of-repeats (FR) element. Through a proteomic approach, we
      previously identified an interaction between EBNA1 and the histone chaperone
      nucleophosmin. Here we show that the EBNA1-nucleophosmin interaction is direct
      and requires the Gly-Arg-rich sequences that contribute to transactivation.
      Additionally, nucleophosmin is recruited by EBNA1 to the FR element and is
      required for EBNA1-mediated transcriptional activation. 

PMID- 24284324
TI  - Therapeutic depletion of natural killer cells controls persistent infection.
AB  - Persistent viral infections are associated with host and viral factors that
      impair effective antiviral immunity. Natural killer (NK) cells contribute to
      establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection
      in mice through suppression of virus-specific T cell responses during the first
      few days of infection, but NK cell depletion during those early time points can
      enable severe T cell-mediated immune pathology and death of the host. Here we
      show that long after their peak in cytolytic activation, NK cells continue to
      support viral persistence at later times of infection. Delayed depletion of NK
      cells, 2 to 3 weeks after infection, enhanced virus-specific T cell responses and
      viral control. This enhancing effect of delayed NK cell depletion on antiviral
      immunity, in contrast to early NK cell depletion, was not associated with
      increased morbidity and mortality, and mice quickly regained weight after
      treatment. The efficacy of the depletion depended in part upon the size of the
      original virus inoculum, the viral load at the time of depletion, and the
      presence of CD4 T cells. Each of these factors is an important contributor to the
      degree of CD8 T cell dysfunction during viral persistence. Thus, NK cells may
      continuously contribute to exhaustion of virus-specific T cells during chronic
      infection, possibly by depleting CD4 T cells. Targeting of NK cells could thus be
      considered in combination with blockade of other immunosuppressive pathways, such
      as the interleukin-10 (IL-10) and programmed death 1 (PD-1) pathways, as a
      therapy to cure chronic human infections, including those with HIV or hepatitis C
      virus. IMPORTANCE Persistent virus infections are a major threat to global human
      health. The capacity of viruses, including HIV and hepatitis C virus, to
      overwhelm or subvert host immune responses contributes to a prolonged state of
      dampened antiviral immune functionality, which in turn facilitates viral
      persistence. Recent efforts have focused on therapeutics that can restore the
      effector functions of these functionally exhausted virus-specific T cells in
      order to expedite viral clearance. Here we establish that natural killer (NK)
      cells actively contribute to immune dysfunction and viral persistence at later
      stages of infection. This previously undescribed mechanism of immune suppression
      during chronic infection provides a vital clue for the design of novel
      therapeutic strategies targeting NK cell immunosuppressive activity in order to
      restore immune function and enhance viral control in chronically infected
      individuals. 

PMID- 24284323
TI  - Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo
      characterization in interferon (alphabeta/gamma) receptor double knockout mice.
AB  - Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever
      (BHF), a reemerging and neglected tropical disease associated with high
      mortality. The prototypical strain of MACV, Carvallo, was isolated from a human
      patient in 1963, but minimal in vitro and in vivo characterization has been
      reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV
      from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties
      similar to those of the parental MACV. Both viruses caused similar disease
      development in alpha/beta and gamma interferon receptor knockout mice, including
      neurological disease development and high mortality. In addition, we have
      identified a novel murine model with mortality and neurological disease similar
      to BHF disease reported in humans and nonhuman primates. 

PMID- 24284325
TI  - Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D
      subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive
      guinea pigs.
AB  - A prophylactic vaccine for genital herpes disease remains an elusive goal. We
      report the results of two studies performed collaboratively in different
      laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex
      virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged
      intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2)
      were produced in baculovirus and administered intramuscularly as monovalent or
      bivalent vaccines with CpG and alum. In study 2, gD2 was produced in CHO cells
      and given intramuscularly with monophosphoryl lipid A (MPL) and alum, or gC2 and
      gD2 were produced in glycoengineered Pichia pastoris and administered
      intramuscularly as a bivalent vaccine with Iscomatrix and alum to HSV-1-naive or 
      seropositive guinea pigs. In both studies, immunization boosted neutralizing
      antibody responses to HSV-1 and HSV-2. In study 1, immunization with gC2, gD2, or
      both immunogens significantly reduced the frequency of genital lesions, with the
      bivalent vaccine showing the greatest protection. In study 2, both vaccines were
      highly protective against genital disease in naive and HSV-1-seropositive
      animals. Comparisons between gD2 and gC2/gD2 in study 2 must be interpreted
      cautiously, because different adjuvants, gD2 doses, and antigen production
      methods were used; however, significant differences invariably favored the
      bivalent vaccine. Immunization of naive animals with gC2/gD2 significantly
      reduced the number of days of vaginal shedding of HSV-2 DNA compared with that
      for mock-immunized animals. Surprisingly, in both studies, immunization of HSV-1
      seropositive animals had little effect on recurrent vaginal shedding of HSV-2
      DNA, despite significantly reducing genital disease. 

PMID- 24284326
TI  - Differential inhibitory effects of cyanovirin-N, griffithsin, and scytovirin on
      entry mediated by envelopes of gammaretroviruses and deltaretroviruses.
AB  - The antiviral lectins griffithsin (GRFT), cyanovirin-N (CV-N), and scytovirin
      (SVN), which inhibit several enveloped viruses, including lentiviruses, were
      examined for their ability to inhibit entry mediated by Env proteins of delta-
      and gammaretroviruses. The glycoproteins from human T-cell leukemia virus type 1
      (HTLV-1) were resistant to the antiviral effects of all three lectins. For
      gammaretroviruses, CV-N inhibited entry mediated by some but not all of the
      envelopes examined, whereas GRFT and SVN displayed only little or no effect. 

PMID- 24284327
TI  - The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has
      endonuclease activity.
AB  - Influenza imposes a great burden on society, not only in its seasonal appearance
      that affects both humans and domesticated animals but also through the constant
      threat of potential pandemics. Migratory birds are considered to be the reservoir
      hosts for influenza viruses, but other animals must also be considered. The
      recently identified influenza-like virus genome, from H17N10 in bats, was shown
      to be markedly different from genomes of other known influenza viruses, as both
      its surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) do not have
      canonical functions. However, no studies on other individual proteins from this
      particular virus have been reported until now. Here, we describe the structure of
      the N-terminal domain of PA from H17N10 influenza-like virus at 2.7-A resolution
      and show that it has a fold similar to those of homologous PA domains present in
      more familiar influenza A virus strains. Moreover, we demonstrate that it
      possesses endonuclease activity and that the histidine residue in the active site
      is essential for this activity. Although this particular influenza virus subtype
      is probably not infectious for humans (even its virus state has not been
      confirmed in bats, as only the genome has been sequenced), reassortment of
      canonical influenza viruses with certain segments from H17N10 cannot be ruled out
      at this stage. Therefore, further studies are urgently needed for the sake of
      influenza prevention and control. 

PMID- 24284330
TI  - The association between dietary lifestyles and hepatocellular injury in Japanese
      workers.
AB  - Elevated alanine aminotransferase (ALT) in serum, relevant to nonalcoholic fatty
      liver disease, has been often reported from Asian countries and the U.S., and it
      may be associated with lifestyle behavior. To clarify whether specific dietary
      behavior is associated with hepatocellular injury, we explored liver markers and
      dietary lifestyles (e.g., breakfast-skipping, eating for lunch, and snacking) in
      1,809 male employees, aged 19-59 years, belonging to a health insurance union of
      automobile dealerships in Japan. ALT, gamma-glutamyltransferase, and asparate
      aminotransferase (AST) were positively correlated with age and body mass index
      (BMI) (P < 0.0001). Odds ratios (ORs) of instant noodle ingestion for lunch to
      ALT elevation (> 30 IU/L), after adjusting for possible confounders including
      age, BMI, and drinking, were 1.33 (95% confidence interval, 1.01-1.75) at 1-2
      times/week and 1.47 (1.07-2.01) at >= 3 times/week, compared to those who seldom
      ate instant noodles. Likewise, the OR of the ingestion at >= 3 times/week to
      gamma-glutamyltransferase elevation (> 50 IU/L) was 1.42 (1.02-1.99), but the OR
      to elevated AST (> 30 IU/L) was not statistically significant. Habitual ethanol
      intake was significantly associated with hepatocellular injury, though the
      threshold of daily ethanol intake differed among liver markers. Despite the low
      OR, habitual instant noodle ingestion for lunch is associated with ALT elevation.
      Since the average content of saturated fatty acids in instant noodles is
      considerably high among cereal foods in Japan, workers with this habit should be
      advised to avoid having unbalanced diets. 

PMID- 24284328
TI  - Identification and characterization of antibody-binding epitopes on the norovirus
      GII.3 capsid.
AB  - Genotype II.3 (GII.3) noroviruses are a major cause of sporadic gastroenteritis,
      particularly in children. The greater incidence of GII.3 noroviruses in the
      pediatric population compared to the adult demographic suggests development of
      herd immunity to this genotype, possibly as a consequence of limited evolution of
      immune epitopes. This study aimed to identify and characterize immune epitopes on
      the GII.3 capsid protein and to determine the level of immune cross-reactivity
      within the genotype. A panel of seven GII.3 virus-like particles (VLPs),
      representing norovirus strains isolated during 1975 to 2008, was tested by enzyme
      linked immunosorbent assay (ELISA) for reactivity with human sera and a rabbit
      anti-GII.3 strain-specific polyclonal serum generated against the 2008 GII.3 VLP.
      Immunoprecipitation of protease-digested GII.3 VLPs and sequencing of bound
      peptides via mass spectrometry were used to locate epitopes on the capsid. Two
      epitopes were investigated further using Mimotopes technology. Serum binding
      studies demonstrated complete intragenotype GII.3 cross-reactivity using both
      human and rabbit serum. Six immunoreactive regions containing epitopes were
      located on the GII.3 capsid protein, two within each capsid domain. Epitopes in
      the S and P1 domains were highly conserved within GII.3 noroviruses. P2 domain
      epitopes were variable and contained evolutionarily important residues and histo
      blood group antigen (HBGA) binding residues. In conclusion, anti-GII.3 antibody
      binding epitopes are highly cross-reactive and mostly conserved within GII.3
      strains. This may account for the limited GII.3 prevalence in adults and suggests
      that a GII.3 strain may be a valuable inclusion in a multivalent pediatric
      targeted VLP vaccine. Exploration of norovirus immune epitopes is vital for
      effective vaccine design. IMPORTANCE This study represents an important
      contribution to the understanding of norovirus immunology in a pediatric
      genotype. The high cross-reactivity and conservation of GII.3 epitopes suggest
      development of herd immunity against GII.3 and indicate that a GII.3 strain would
      be a valuable inclusion in a pediatric targeted multivalent vaccine.
      Immunological understanding of pediatric norovirus strains is important since
      norovirus vaccines will likely target high-risk groups such as the pediatric
      population. 

PMID- 24284331
TI  - Instabilities of Teflon AF thin films in alumina nanochannels and adhesion of bi
      level Teflon AF nanopillars.
AB  - In this paper, a novel replica-molding technique for fabrication of bi-level
      Teflon AF nanopillars, as an electrostatic-based dry adhesive, is reported. The
      technique reported herein relies on the concurrent heating and cooling of the
      Teflon AF melt which filled vertically aligned alumina nanochannels as the mold.
      Unlike conventional polymer infiltration methods which consist of filling the
      mold by only heating the polymer above its glass transition temperature, in the
      current method, the polymer melt was also simultaneously cooled down during the
      infiltration process. Concurrent cooling of the Teflon AF melt allowed control
      over the interfacial instabilities of the polymer thin film, which formed ahead
      of the polymer melt upon its infiltration into the alumina nanochannels. By doing
      so, the geometrical properties of the peculiar fluffy nanostructure which was
      subsequently developed-after removal of the mold-on top of the extremely high
      aspect-ratio Teflon AF nanopillars (200 nm in diameter, ~25 MUm tall) were
      modified. The height of the base nanopillars was measured and the structural
      properties (i.e., surface area fraction and roughness) of the fluffy
      nanostructure terminating the base nanopillars at the tip were quantified. Next,
      the effects of the topographical properties of the bi-level Teflon AF nanopillars
      on their adhesion, in both the normal and shear directions, were investigated.
      Tribological results were discussed in detail to clarify the contribution of the
      structural properties of the fabricated dry adhesive toward its remarkable
      adhesion and friction forces generated via contact electrification. It is
      worthwhile to mention that bi-level Teflon AF nanopillars with these specific
      structural properties have generated enhanced adhesion and friction strengths, up
      to ~2.1 and 13 N cm(-2), respectively.

PMID- 24284329
TI  - Evidence of pervasive biologically functional secondary structures within the
      genomes of eukaryotic single-stranded DNA viruses.
AB  - Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of
      forming complex secondary structures through Watson-Crick base pairing between
      their constituent nucleotides. A few of the structural elements formed by such
      base pairings are, in fact, known to have important functions during the
      replication of many ssDNA viruses. Unknown, however, are (i) whether numerous
      additional ssDNA virus genomic structural elements predicted to exist by
      computational DNA folding methods actually exist and (ii) whether those
      structures that do exist have any biological relevance. We therefore
      computationally inferred lists of the most evolutionarily conserved structures
      within a diverse selection of animal- and plant-infecting ssDNA viruses drawn
      from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and
      Geminiviridae and analyzed these for evidence of natural selection favoring the
      maintenance of these structures. While we find evidence that is consistent with
      purifying selection being stronger at nucleotide sites that are predicted to be
      base paired than at sites predicted to be unpaired, we also find strong
      associations between sites that are predicted to pair with one another and site
      pairs that are apparently coevolving in a complementary fashion. Collectively,
      these results indicate that natural selection actively preserves much of the
      pervasive secondary structure that is evident within eukaryote-infecting ssDNA
      virus genomes and, therefore, that much of this structure is biologically
      functional. Lastly, we provide examples of various highly conserved but
      completely uncharacterized structural elements that likely have important
      functions within some of the ssDNA virus genomes analyzed here. 

PMID- 24284332
TI  - Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and
      MGMT expression on dacarbazine resistance of Hodgkin's lymphoma cells.
AB  - We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase
      (MGMT) promoter and mRNA expression in HL cells and assessed the response of
      these cells to dacarbazine. Expression of MGMT correlated with the presence of
      non-methylated promoters and cell lines with non-methylated promoters showed
      increased resistance against dacarbazine. KM-H2 cells expressed fusion
      transcripts between MGMT and proline-rich coiled-coil 2B (PRRC2B) but no wild
      type MGMT transcripts. Dacarbazine sensitivity suggested that fusion transcripts
      are translated into a protein with reduced functionality. MGMT promoter
      methylation predicts dacarbazine sensitivity of HL cells and it might be
      interesting to analyze this factor in HL patients. 

PMID- 24284333
TI  - Discrepancy in diagnosis of primary myelofibrosis between referral and tertiary
      care centers.
AB  - Primary myelofibrosis (PMF) is myeloproliferative neoplasm whose diagnosis is
      based on a combination of clinical and pathology criteria. We evaluated 560
      consecutive patients who were diagnosed with PMF upon a referral to our center
      and evaluated the frequency of and reasons for diagnostic discordance.
      Discordance in the diagnosis was found in 70 (12.5%) patients. Discordant cases
      had a significantly lower grade of bone marrow fibrosis (grade 0-1), more likely
      to be JAK2V617F-mutation negative, and have no peripheral blood blasts, possibly
      explaining the difficulty in making a proper diagnosis and underscoring the need
      for a complete evaluation at a tertiary center. 

PMID- 24284334
TI  - ZFYVE26/SPASTIZIN: a close link between complicated hereditary spastic
      paraparesis and autophagy.
AB  - Defective autophagy is associated with neurodegenerative disorders including
      Alzheimer, Parkinson and Huntington diseases, amyotrophic lateral sclerosis and
      SCA (spinocerebellar ataxias). Autophagy defects were detected also in SPG49, a
      complicated form of hereditary spastic paraparesis (cHSP) associated with
      mutations in the TECPR2 gene, suggesting a role of autophagy also in this
      heterogeneous group of neurodegenerative diseases. We recently found defective
      autophagy in SPG15, another HSP subtype associated with mutations in the
      ZFYVE26/SPG15 gene. Patient-derived cells (fibroblasts/lymphoblasts) carrying
      different ZFYVE26 mutations show accumulation of immature autophagosomes and
      increased MAP1LC3B-II and SQSTM1/p62 levels. These findings indicate that ZFYVE26
      is a key determinant of autophagosome maturation, which is impaired when the
      protein is defective or absent. Replication of these findings in primary neurons
      supports the relevance of defective autophagy in SPG15-related neurodegeneration.

PMID- 24284335
TI  - Chitosan coupling makes microbial biofilms susceptible to antibiotics.
AB  - Microbial biofilms, prevalent in nature and inherently resistant to both
      antimicrobial agents and host defenses, can cause serious problems in the
      chemical, medical and pharmaceutical industries. Herein we demonstrated that
      conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could
      efficiently damage established biofilms and inhibit biofilm formation. This
      method was suitable to eradiate biofilms formed by Gram-positive organisms, and
      it appeared that antibiotic contents, molecular size and positive charges of the
      conjugate were the key to retain this anti-biofilm activity. Mechanistic insight
      demonstrated chitosan conjugation rendered streptomycin more accessible into
      biofilms, thereby available to interact with biofilm bacteria. Thus, this work
      represent an innovative strategy that antibiotic covalently linked to
      carbohydrate carriers can overcome antibiotic resistance of microbial biofilms,
      and might provide a comprehensive solution to combat biofilms in industrial and
      medical settings. 

PMID- 24284337
TI  - Simon Wessely: a man with "a joking seriousness".

PMID- 24284336
TI  - Mortality rates at 10 years after metal-on-metal hip resurfacing compared with
      total hip replacement in England: retrospective cohort analysis of hospital
      episode statistics.
AB  - OBJECTIVES: To compare 10 year mortality rates among patients undergoing metal-on
      metal hip resurfacing and total hip replacement in England. DESIGN: Retrospective
      cohort study. SETTING: English hospital episode statistics database linked to
      mortality records from the Office for National Statistics. POPULATION: All adults
      who underwent primary elective hip replacement for osteoarthritis from April 1999
      to March 2012. The exposure of interest was prosthesis type: cemented total hip
      replacement, uncemented total hip replacement, and metal-on-metal hip
      resurfacing. Confounding variables included age, sex, Charlson comorbidity index,
      rurality, area deprivation, surgical volume, and year of operation. MAIN OUTCOME
      MEASURES: All cause mortality. Propensity score matching was used to minimise
      confounding by indication. Kaplan-Meier plots estimated the probability of
      survival up to 10 years after surgery. Multilevel Cox regression modelling,
      stratified on matched sets, described the association between prosthesis type and
      time to death, accounting for variation across hospital trusts. RESULTS: 7437
      patients undergoing metal-on-metal hip resurfacing were matched to 22,311
      undergoing cemented total hip replacement; 8101 patients undergoing metal-on
      metal hip resurfacing were matched to 24,303 undergoing uncemented total hip
      replacement. 10 year rates of cumulative mortality were 271 (3.6%) for metal-on
      metal hip resurfacing versus 1363 (6.1%) for cemented total hip replacement, and
      239 (3.0%) for metal-on-metal hip resurfacing versus 999 (4.1%) for uncemented
      total hip replacement. Patients undergoing metal-on-metal hip resurfacing had an
      increased survival probability (hazard ratio 0.51 (95% confidence interval 0.45
      to 0.59) for cemented hip replacement; 0.55 (0.47 to 0.65) for uncemented hip
      replacement). There was no evidence for an interaction with age or sex.
      CONCLUSIONS: Patients with hip osteoarthritis undergoing metal-on-metal hip
      resurfacing have reduced mortality in the long term compared with those
      undergoing cemented or uncemented total hip replacement. This difference
      persisted after extensive adjustment for confounding factors available in our
      data. The study results can be applied to matched populations, which exclude
      patients who are very old and have had complex total hip replacements. Although
      residual confounding is possible, the observed effect size is large. These
      findings require validation in external cohorts and randomised clinical trials.

PMID- 24284338
TI  - The importance of the osmolality gap in ethylene glycol intoxication.

PMID- 24284339
TI  - Labelled for life.

PMID- 24284340
TI  - Patient confidentiality in a time of care.data.

PMID- 24284341
TI  - Half of English hospital doctors fear raising concerns, finds survey.

PMID- 24284342
TI  - Regulators should do more to protect whistleblowers, commission says.

PMID- 24284343
TI  - Bioabsorbable drug eluting stent: winner or sinner?

PMID- 24284344
TI  - Target cardiovascular risk rather than cholesterol concentration.

PMID- 24284345
TI  - E-cigarette marketing is aimed at youngsters, says charity.

PMID- 24284346
TI  - Regulator wants to do more to help prevent NHS trusts getting into trouble.

PMID- 24284347
TI  - FDA halts sale of genetic test sold to consumers.

PMID- 24284348
TI  - Tobacco smoke exposure during childhood: effect on cochlear physiology.
AB  - The rate of smoking in Brazil is about 18.8%. Exposure to environmental tobacco
      smoke is one of the major factors predisposing children to several hazardous
      health problems. The objective of the present research was to analyze the effect
      of tobacco smoke exposure during childhood on cochlear physiology by measuring
      the transient evoked otoacoustic emissions (TEOAE) response levels. Cotinine, the
      main metabolite of nicotine, was measured in 145 students' (8-10 years old)
      urine. Sixty students indicated tobacco smoke exposure (TSE) (cotinine urine
      levels >= 5.0 ng/mL) and 85 did not. The evaluation of TEOAE of TSE students
      showed lower response levels, mainly on frequencies of 2.8 kHz on the right and
      left ears and 2.0 kHz on left ear and lower signal noise response levels, mainly
      on the 1.0 kHz and 1.4 kHz frequencies, when compared to controls that were not
      exposed to tobacco. The mean reduction observed in TEOAE of tobacco smoke
      exposure children was 2.1 dB SPL. These results have important implications on
      the damage to the cochlear structures and indicate a possible loss in hearing and
      hearing ability development. 

PMID- 24284349
TI  - Automatic assessment of socioeconomic impact on cardiac rehabilitation.
AB  - Disability-Adjusted Life Years (DALYs) and Quality-Adjusted Life Years (QALYs),
      which capture life expectancy and quality of the remaining life-years, are
      applied in a new method to measure socioeconomic impacts related to health. A 7
      step methodology estimating the impact of health interventions based on DALYs,
      QALYs and functioning changes is presented. It relates the latter (1) to the EQ
      5D-5L questionnaire (2) to automatically calculate the health status before and
      after the intervention (3). This change of status is represented as a change in
      quality of life when calculating QALYs gained due to the intervention (4). In
      order to make an economic assessment, QALYs gained are converted to DALYs averted
      (5). Then, by inferring the cost/DALY from the cost associated to the disability
      in terms of DALYs lost (6) and taking into account the cost of the action, cost
      savings due to the intervention are calculated (7) as an objective measure of
      socioeconomic impact. The methodology is implemented in Java. Cases within the
      framework of cardiac rehabilitation processes are analyzed and the calculations
      are based on 200 patients who underwent different cardiac-rehabilitation
      processes. Results show that these interventions result, on average, in a gain in
      QALYs of 0.6 and a cost savings of 8,000 ?. 

PMID- 24284350
TI  - The dynamic growth exhibition and accumulation of cadmium of Pak choi (Brassica
      campestris L. ssp. chinensis) grown in contaminated soils.
AB  - The accumulation of heavy metals, especially cadmium (Cd), in leafy vegetables
      was compared with other vegetables. Pak choi (Brassica campestris L. ssp.
      chinensis) is a leafy vegetable consumed in Taiwan and its safety for consumption
      after growing in contaminated soils is a public concern. A pot experiment (50
      days) was conducted to understand the dynamic accumulation of Cd by pak choi
      grown in artificially contaminated soils. The edible parts of pak choi were
      sampled and analyzed every 2-3 days. The dry weight (DW) of pak choi was an
      exponential function of leaf length, leaf width, and chlorophyll content. The
      accumulation of Cd increased when the soil Cd concentration was raised, but was
      kept at a constant level during different growth stages. Pak choi had a high
      bioconcentration factor (BCF = ratio of the concentration in the edible parts to
      that in the soils), at values of 3.5-4.0. The consumption of pak choi grown in
      soils contaminated at levels used in this study would result in the ingestion of
      impermissible amounts of Cd and could possibly have harmful effects on health. 

PMID- 24284351
TI  - Risk selection, risk adjustment and choice: concepts and lessons from the
      Americas.
AB  - Interest has grown worldwide in risk adjustment and risk sharing due to their
      potential to contain costs, improve fairness, and reduce selection problems in
      health care markets. Significant steps have been made in the empirical
      development of risk adjustment models, and in the theoretical foundations of risk
      adjustment and risk sharing. This literature has often modeled the effects of
      risk adjustment without highlighting the institutional setting, regulations, and
      diverse selection problems that risk adjustment is intended to fix. Perhaps
      because of this, the existing literature and their recommendations for optimal
      risk adjustment or optimal payment systems are sometimes confusing. In this
      paper, we present a unified way of thinking about the organizational structure of
      health care systems, which enables us to focus on two key dimensions of markets
      that have received less attention: what choices are available that may lead to
      selection problems, and what financial or regulatory tools other than risk
      adjustment are used to influence these choices. We specifically examine the
      health care systems, choices, and problems in four countries: the US, Canada,
      Chile, and Colombia, and examine the relationship between selection-related
      efficiency and fairness problems and the choices that are allowed in each
      country, and discuss recent regulatory reforms that affect choices and selection
      problems. In this sample, countries and insurance programs with more choices have
      more selection problems. 

PMID- 24284352
TI  - Post-traumatic stress disorder and urban violence: an anthropological study.
AB  - The study aimed to understand how "distress" is experienced by patients with Post
      Traumatic Stress Disorder (PTSD) in the social-cultural context of Sao Paulo,
      Brazil, an urban environment marked by social inequality and high levels of
      violence. A qualitative study was conducted between 2008 and 2010 with PTSD
      patients (F43.1, ICD-10, 1997) who had been victims of robberies and kidnappings
      in Sao Paulo. Dense ethnographic observations were carried out, as well as in
      depth semi-structured interviews with ten adult patients. The analysis method
      used was based on anthropology. The results show that it is particularly
      important to distinguish between perceptions of different forms of the experience
      of social suffering and perceptions of health and illness held by victims and
      biomedical experts. The cause of PTSD is more often associated with the personal
      problems of the victim than with the specific traumatic event. The distress
      described in terms of what is considered a "normal" reaction to violence and what
      is considered a symptom of PTSD. The findings indicate that the diagnostic of
      PTSD can be understood in relation to the different contexts within a culture.
      The ethnographic approach serves not only to illuminate individual suffering but
      also the social suffering experienced by the residents of Sao Paulo. 

PMID- 24284353
TI  - Suitability of optical, physical and chemical measurements for detection of
      changes in bacterial drinking water quality.
AB  - In this study, different optical, physical and chemical measurements were tested
      for their capacity to detect changes in water quality. The tests included UV
      absorbance at 254 nm, absorbance at 420 nm, turbidity, particle counting,
      temperature, pH, electric conductivity (EC), free chlorine concentration and ATP
      concentration measurements. Special emphasis was given to investigating the
      potential for measurement tools to detect changes in bacterial concentrations in
      drinking water. Bacterial colony counts (CFU) and total bacterial cell counts
      (TBC) were used as reference methods for assessing the bacterial water quality.
      The study consists of a series of laboratory scale experiments: monitoring of
      regrowth of Pseudomonas fluorescens, estimation of the detection limits for
      optical measurements using Escherichia coli dilutions, verification of the
      relationships by analysing grab water samples from various distribution systems
      and utilisation of the measurements in the case of an accidentally contaminated
      distribution network. We found significant correlations between the tested
      measurements and the bacterial water quality. As the bacterial contamination of
      water often co-occurs with the intrusion of matrixes containing mainly non
      bacterial components, the tested measurement tools can be considered to have the
      potential to rapidly detect any major changes in drinking water quality. 

PMID- 24284354
TI  - The impact of family history of allergy on risk of food allergy: a population
      based study of infants.
AB  - The apparent rapid increase in IgE-mediated food allergy and its implications are
      now widely recognized, but little is known about the relationship between family
      history (an indirect measure of genetic risk) and the risk of food allergy. In a
      population-based study of 5,276 one year old infants (HealthNuts), the prevalence
      of oral food challenge-confirmed food allergy was measured. Associations between
      family history of allergic disease and food allergy in infants were examined
      using multiple logistic regression. Food allergy was diagnosed in 534 infants.
      Compared to those with no family history of allergic disease, children meeting
      the current definition of "high risk" for allergic disease (one immediate family
      member with a history of any allergic disease) showed only a modest increase (OR
      1.4, 95% CI 1.1-1.7) in food allergy, while having two or more allergic family
      members was more strongly predictive of food allergy in the child (OR 1.8, 95% CI
      1.5-2.3). There were also differences in the associations between family history
      and egg and peanut allergy in the child. Re-defining "high risk" as two or more
      allergic family members may be more useful for identification of groups with a
      significantly increased risk of food allergy both clinically and within research
      studies. 

PMID- 24284355
TI  - Is household air pollution a risk factor for eye disease?
AB  - In developing countries, household air pollution (HAP) resulting from the
      inefficient burning of coal and biomass (wood, charcoal, animal dung and crop
      residues) for cooking and heating has been linked to a number of negative health
      outcomes, mostly notably respiratory diseases and cancers. While ocular
      irritation has been associated with HAP, there are sparse data on adverse ocular
      outcomes that may result from acute and chronic exposures. We consider that there
      is suggestive evidence, and biological plausibility, to hypothesize that HAP is
      associated with some of the major blinding, and painful, eye conditions seen
      worldwide. Further research on this environmental risk factor for eye diseases is
      warranted. 

PMID- 24284357
TI  - Age-related changes in physical fall risk factors: results from a 3 year follow
      up of community dwelling older adults in Tasmania, Australia.
AB  - As the population ages, fall rates are expected to increase, leading to a rise in
      accidental injury and injury-related deaths, and placing an escalating burden on
      health care systems. Sixty-nine independent community-dwelling adults (60-85
      years, 18 males) had their leg strength, physical activity levels and their
      annual fall rate assessed at two timepoints over three years, (summer 2010 and
      summer 2013) monitoring balance. Force platform measures of medio-lateral sway
      range increased significantly under conditions of eyes open (mean difference MD
      2.5 cm; 95% CI 2.2 to 2.8 cm) and eyes closed (MD 3.2 cm; 95% CI 2.8 to 3.6 cm),
      respectively (all p < 0.001) indicating worsening static balance control. Dynamic
      balance showed similar changes (p < 0.036). Leg strength was not significantly
      different between visits (p > 0.26). Physical activity reduced significantly (MD 
      909 Cal/week; 95% CI -347 to -1,470 Cal/week; p = 0.002) during the course of the
      study. Participants maintained aerobic activities, however resistance and balance
      exercise levels decreased non-significantly. The likelihood of falling was higher
      at the end of the study compared to the first timepoint (odds ratio 1.93, 95% CI
      0.94 to 3.94; p = 0.07). Results of this study indicate that despite maintenance
      of leg strength there was an increase in medio-lateral sway over a relatively
      short time frame, with higher than expected increases in fall rates. 

PMID- 24284356
TI  - Exploring the spatio-temporal dynamics of reservoir hosts, vectors, and human
      hosts of West Nile virus: a review of the recent literature.
AB  - Over the last two decades West Nile Virus (WNV) has been responsible for
      significant disease outbreaks in humans and animals in many parts of the World.
      Its extremely rapid global diffusion argues for a better understanding of its
      geographic extent. The purpose of this inquiry was to explore spatio-temporal
      patterns of WNV using geospatial technologies to study populations of the
      reservoir hosts, vectors, and human hosts, in addition to the spatio-temporal
      interactions among these populations. Review of the recent literature on spatial
      WNV disease risk modeling led to the conclusion that numerous environmental
      factors might be critical for its dissemination. New Geographic Information
      Systems (GIS)-based studies are monitoring occurrence at the macro-level, and
      helping pinpoint areas of occurrence at the micro-level, where geographically
      targeted, species-specific control measures are sometimes taken and more
      sophisticated methods of surveillance have been used. 

PMID- 24284358
TI  - Twelve-months follow-up of supervised exercise after percutaneous transluminal
      angioplasty for intermittent claudication: a randomised clinical trial.
AB  - The aim of this study was to explore the effects during 12 months follow-up of 12
      weeks of supervised exercise therapy (SET) after percutaneous transluminal
      angioplasty (PTA) compared to PTA alone on physical function, limb hemodynamics
      and health-related quality of life (HRQoL) in patients with intermittent
      claudication. Fifty patients were randomised to an intervention or a control
      group. Both groups received usual post-operative care and follow-up measurements
      at three, six and 12 months after PTA. The intervention group performed 12 weeks
      of SET after PTA. The control group did not receive any additional follow-up
      regarding exercise. During the 12 months' follow-up, the members of the
      intervention group had significantly better walking distance than the control
      group. The intervention group had a significantly higher HRQoL score in the
      physical component score of the SF-36, and the domains of physical function,
      bodily pain and vitality. For limb hemodynamics, there was a non-significant
      trend towards better results in the intervention group compared to the control
      group. CONCLUSION: SET after PTA yielded statistically significantly better
      results for walking distance and HRQoL in the intervention group than the control
      group during the 12 months of follow-up.

PMID- 24284359
TI  - Fine particulate air pollution and hospital admissions for chronic obstructive
      pulmonary disease: a case-crossover study in Taipei.
AB  - We undertook this study to investigate whether there is an association between
      atmospheric fine particles (PM2.5) levels and inpatient admissions for chronic
      obstructive pulmonary disease (COPD) in Taipei, Taiwan. Data on inpatient
      admissions for COPD and ambient on air pollution levels in Taipei were obtained
      for years 2006 to 2010. We estimated the relative risk of inpatient admissions
      for COPD using a case-crossover design with the following control variables:
      weather measures, day of the week, seasonality, and long-term time trends. For
      the single-pollutant model (not controlling for other atmospheric pollutants),
      COPD admissions were significantly and positively associated with higher PM2.5
      levels during both warm days (>23  degrees C) and cool days (<23  degrees C),
      with an interquartile range increase of 12% (95% CI = 8-16%) and 3% (95% CI = 0
      7%) in COPD admissions, respectively. In the two-pollutant models, PM2.5 remained
      significant even controlling for SO2 or O3 on both warm and cool days. Taken as a
      whole, our study demonstrates that higher levels of PM2.5 may increase the risk
      of inpatient admissions for COPD. 

PMID- 24284360
TI  - Assessment of infantile mineral imbalances in autism spectrum disorders (ASDs).
AB  - The interactions between genes and the environment are now regarded as the most
      probable explanation for autism. In this review, we summarize the results of a
      metallomics study in which scalp hair concentrations of 26 trace elements were
      examined for 1,967 autistic children (1,553 males and 414 females aged 0-15 years
      old), and discuss recent advances in our understanding of epigenetic roles of
      infantile mineral imbalances in the pathogenesis of autism. In the 1,967
      subjects, 584 (29.7%) and 347 (17.6%) were found deficient in zinc and magnesium,
      respectively, and the incidence rate of zinc deficiency was estimated at 43.5% in
      male and 52.5% in female infantile subjects aged 0-3 years-old. In contrast, 339
      (17.2%), 168 (8.5%) and 94 (4.8%) individuals were found to suffer from high
      burdens of aluminum, cadmium and lead, respectively, and 2.8% or less from
      mercury and arsenic. High toxic metal burdens were more frequently observed in
      the infants aged 0-3 years-old, whose incidence rates were 20.6%, 12.1%, 7.5%,
      3.2% and 2.3% for aluminum, cadmium, lead, arsenic and mercury, respectively.
      These findings suggest that infantile zinc- and magnesium-deficiency and/or toxic
      metal burdens may be critical and induce epigenetic alterations in the genes and
      genetic regulation mechanisms of neurodevelopment in the autistic children, and
      demonstrate that a time factor "infantile window" is also critical for
      neurodevelopment and probably for therapy. Thus, early metallomics analysis may
      lead to early screening/estimation and treatment/prevention for the autistic
      neurodevelopment disorders. 

PMID- 24284361
TI  - Common and rare single nucleotide polymorphisms in the LDLR gene are present in a
      black South African population and associate with low-density lipoprotein
      cholesterol levels.
AB  - The LDL receptor has an essential role in regulating plasma LDL-C levels. Genetic
      variation in the LDLR gene can be associated with either lower or moderately
      raised plasma levels of LDL-C, or may cause familial hypercholesterolemia. The
      prevalence of single-nucleotide polymorphisms (SNPs) in the LDLR in the black
      South African population is not known and therefore, we aimed to determine the
      genotypic variation of the LDLR in the study population as well as to define the
      association of the different genotypes with plasma LDL-C levels. A random
      selection of 1860 apparently healthy black South African volunteers aged 35-60
      years was made in a cross-sectional study. Novel SNPs were identified in a subset
      of 30 individuals by means of automated sequencing before screening the entire
      cohort by means of the Illumina VeraCode GoldenGate Genotyping Assay on a
      BeadXpress Reader system. Twenty-five SNPs were genotyped, two of which were
      novel. A very rare SNP, rs17249141, in the promoter region was significantly
      associated with lower levels of LDL-C. Four other SNPs (rs2738447, rs14158,
      rs2738465 and rs3180023) were significantly associated with increased levels of
      LDL-C. We can conclude that some of the various SNPs identified do indeed
      associate with LDL-C levels. 

PMID- 24284362
TI  - The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and
      invasion by targeting GOLM1 in prostate cancer.
AB  - Our recent study of microRNA (miRNA) expression signature of prostate cancer
      (PCa) has revealed that the microRNA-143/145 (miR-143/145) cluster is
      significantly downregulated in cancer tissues, suggesting that these cluster
      miRNAs are candidate tumor suppressors. The aim of this study was to investigate
      the functional significance of the miR-143/145 cluster in PCa cells and to
      identify novel targets regulated by these cluster miRNAs in PCa. Restoration of
      miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs
      significantly inhibited cancer cell migration and invasion. Gene expression data
      and in silico analysis demonstrated that Golgi membrane protein 1 (GOLM1)
      resembling a type II golgi transmembrane protein was a potential target of miR
      143/145 cluster target gene. Gene expression studies and luciferase reporter
      assays showed that GOLM1 was directly regulated by the miR-143/145 cluster.
      Silencing of GOLM1 resulted in significant inhibition of cell migration and
      invasion in PCa cells. Furthermore, the expression of GOLM1 was upregulated in
      cancer tissues by immunohistochemistry. Loss of the tumor-suppressive miR-143/145
      cluster enhanced cancer cell migration and invasion in PCa through directly
      regulating GOLM1. Our data on target genes regulated by the tumor-suppressive miR
      143/145 cluster provide new insights into the potential mechanisms of PCa
      oncogenesis and metastasis. 

PMID- 24284363
TI  - Molecular analysis of potassium ion channel genes in sudden death cases among
      patients administered psychotropic drug therapy: are polymorphisms in LQT genes a
      potential risk factor?
AB  - Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS).
      Unexpected autopsy-negative sudden death in patients taking psychotropic drugs
      may be associated with prolonged QT intervals and life-threatening arrhythmias.
      We analyzed genes that encode for cardiac ion channels and potentially associated
      with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in
      10 cases of sudden death involving patients administered psychotropic medication
      in which autopsy findings identified no clear cause of death. We amplified and
      sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism
      in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381
      healthy Japanese individuals carry this polymorphism. Reports of previous
      functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium
      channel protein causes mild I(Ks) channel dysfunction. Our present study suggests
      that administering psychotropic drug therapy to individuals carrying the G643S
      polymorphism may heighten the risk of prolonged QT intervals and life-threatening
      arrhythmias. Thus, screening for the G643S polymorphism before prescribing
      psychotropic drugs may help reduce the risk of unexpected sudden death.

PMID- 24284364
TI  - PLS3 expression and SMA phenotype: a commentary on correlation of PLS3 expression
      with disease severity in children with spinal muscular atrophy.

PMID- 24284365
TI  - Age-related alterations in the metabolic profile in the hippocampus of the
      senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse
      model.
AB  - Alzheimer's disease (AD), the most common age-dependent neurodegenerative
      disorder, produces a progressive decline in cognitive function. The metabolic
      mechanism of AD has emerged in recent years. In this study, we used multivariate
      analyses of gas chromatography-mass spectrometry measurements to determine that
      learning and retention-related metabolic profiles are altered during aging in the
      hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in
      17 metabolites were detected in mature and aged mice compared to young mice (13
      decreased and 4 increased metabolites), including metabolites related to
      dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid,
      and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine,
      aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related
      metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid),
      and other altered metabolites (increased N-acetyl-aspartic acid and decreased
      pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these
      alterations indicated that the metabolic mechanisms of age-related cognitive
      impairment in SAMP8 mice were related to multiple pathways and networks. Lipid
      metabolism, especially cholesterol metabolism, appears to play a distinct role in
      the hippocampus in AD.

PMID- 24284366
TI  - Dementia in middle-aged patients with schizophrenia.
AB  - BACKGROUND: Although numerous studies have assessed cognitive dysfunction in
      patients with schizophrenia, very few have focused on the diagnosis of dementia.
      OBJECTIVE: Our objectives were to accurately diagnose dementia in a cohort of
      middle-aged patients with schizophrenia and to assess the type of dementia.
      METHODS: 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged
      50 to 70 years, underwent a psychiatric, neurological, and neuropsychological
      evaluation at baseline and after a 20-month follow-up. We established a 3-step
      procedure: 1) diagnose dementia according to the DSM-IV criteria, using the
      Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize
      dementia using brain imaging, perfusion by 99mTc-ECD-SPECT and laboratory tests
      including Alzheimer's disease cerebrospinal fluid biomarkers; and 3) search for
      genetic determinants. RESULTS: Fourteen patients fulfilled the diagnostic
      criteria of dementia. Four were diagnosed with possible or probable behavioral
      variant frontotemporal dementia (bvFTD), two with probable Alzheimer's disease,
      two with probable vascular dementia (including one due to CADASIL), one with CNS
      inflammatory disease, and six could not be fully characterized. CONCLUSIONS: The
      diagnosis of dementia in middle-aged patients with schizophrenia is challenging
      but possible, using a multistep procedure. The most frequent condition, bvFTD,
      could reflect the presence of an evolutive neurodegenerative process in some
      patients.

PMID- 24284367
TI  - In vitro evidence that an aqueous extract of Centella asiatica modulates alpha
      synuclein aggregation dynamics.
AB  - alpha-Synuclein aggregation is one of the major etiological factors implicated in
      Parkinson's disease (PD). The prevention of aggregation of alpha-synuclein is a
      potential therapeutic intervention for preventing PD. The discovery of natural
      products as alternative drugs to treat PD and related disorders is a current
      trend. The aqueous extract of Centella asiatica (CA) is traditionally used as a
      brain tonic and CA is known to improve cognition and memory. There are limited
      data on the role of CA in modulating amyloid-beta (Abeta) levels in the brain and
      in Abeta aggregation. Our study focuses on CA as a modulator of the alpha
      synuclein aggregation pattern in vitro. Our investigation is focused on: (i)
      whether the CA leaf aqueous extract prevents the formation of aggregates from
      monomers (Phase I: alpha-synuclein + extract co-incubation); (ii) whether the CA
      aqueous extract prevents the formation of fibrils from oligomers (Phase II:
      extract added after oligomers formation); and (iii) whether the CA aqueous
      extract disintegrates the pre-formed fibrils (Phase III: extract added to mature
      fibrils and incubated for 9 days). The aggregation kinetics are studied using a
      thioflavin-T assay, circular dichroism, and transmission electron microscopy. The
      results showed that the CA aqueous extract completely inhibited the alpha
      synuclein aggregation from monomers. Further, CA extract significantly inhibited
      the formation of oligomer to aggregates and favored the disintegration of the
      preformed fibrils. The study provides an insight in finding new natural products
      for future PD therapeutics. 

PMID- 24284368
TI  - The new Qualitative Scoring MMSE Pentagon Test (QSPT) as a valid screening tool
      between autopsy-confirmed dementia with Lewy bodies and Alzheimer's disease.
AB  - Visual-constructional apraxia is a prominent feature of dementia with Lewy bodies
      (DLB) that might help to clinically distinguish it from Alzheimer's disease (AD).
      The main goal of this study was to assess performance on the copy intersecting
      pentagon item of the Mini-Mental State Examination with the new Qualitative
      Scoring method for the Pentagon copy Test (QSPT). In order to determine which
      aspects of the drawings might differentiate DLB from AD, pentagon drawings of
      autopsy-verified DLB (n = 16) and AD (n = 15) patients were assessed using the
      QSPT. The qualitative scoring encompasses the assessment of different parameters
      of the drawing, such as number of angles, distance/intersection, closure/opening,
      rotation, and closing-in. The QSPT scores were compared between groups using
      linear analyses and artificial neural network analyses at four different time
      points. Linear analyses showed that during the first evaluation, number of angles
      was the only parameter that showed a significant difference between DLB and AD
      patients. A gradual decline in other parameters and total pentagon score occurred
      in both groups during subsequent years, with greater decline for the DLB group.
      The artificial neural network analyses using auto-contractive maps showed that,
      with disease progression, DLB became related to relatively lower qualitative
      pentagon scores, whereas AD became related to relatively higher qualitative
      scores. These findings suggest that the QSPT might be a sensitive measure of
      visuo-constructive abilities able to differentiate DLB from AD at disease onset
      and as the diseases progress, but further studies on larger population are
      necessary in order to establish its clinical relevance.

PMID- 24284369
TI  - Analysis of breath volatile organic compounds as a noninvasive tool to diagnose
      nonalcoholic fatty liver disease in children.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is one of the most common
      complications of childhood obesity. Our objective was to investigate the
      association of breath volatile organic compounds with the diagnosis of NAFLD in
      children. METHODS: Patients were screened with an ultrasound of the abdomen to
      evaluate for NAFLD. Exhaled breath was collected and analyzed per protocol using
      selective ion flow tube mass spectrometry (SIFT-MS). RESULTS: Sixty patients were
      included in the study (37 with NAFLD and 23 with normal liver). All children were
      overweight or obese. The mean age was 14.1+/-2.8 years and 50% were female. A
      comparison of the SIFT-MS results of patients with NAFLD with those with normal
      liver on ultrasound revealed differences in concentration of more than 15
      compounds. A panel of four volatile organic compounds can identify the presence
      of NAFLD with good accuracy (area under the receiver operating characteristic
      curve of 0.913 in the training set and 0.763 in the validation set). Breath
      isoprene, acetone, trimethylamine, acetaldehyde, and pentane were significantly
      higher in the NAFLD group compared with normal liver group (14.7 ppb vs. 8.9 for
      isoprene; 71.7 vs. 36.9 for acetone; 5.0 vs. 3.2 for trimethylamine; 35.1 vs.
      26.0 for acetaldehyde; and 13.3 vs. 8.8 for pentane, P<0.05 for all). CONCLUSION:
      Exhaled breath analysis is a promising noninvasive method to detect fatty liver
      in children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are
      novel biomarkers that may help to gain insight into pathophysiological processes
      leading to the development of NAFLD.

PMID- 24284370
TI  - Clinical significance of a scoring formula of liver injury for the preoperative
      evaluation of patients with liver cirrhosis.
AB  - OBJECTIVE: The aim of this study was to establish a clinical scoring formula of
      liver injury (SFLI) using the matter element analysis method, in order to provide
      the necessary information for the preoperative assessment and treatment of liver
      cirrhosis in clinical practice. MATERIALS AND METHODS: We collected preoperative
      information for 12 serum biochemical markers (ALB, PA, TBil, SCr, INR, ALT, AST,
      gamma-GT, ALP, PT, APTT, and TT) from patients with liver cirrhosis,
      statistically analyzed the relationship between the serum biochemical markers and
      the extent of liver injury, and obtained the liver injury scoring formula using
      the matter element analysis method. RESULTS: In our formula, the serum
      biochemical markers of patients with different degrees of liver cirrhosis damage
      led to different R-values, which represented the severity of the disease and the
      liver functional reserve. R=1 indicates that the liver tissue is normal;
      0.770<=R<1 indicates that the liver is in the early stage of cirrhosis (SFLI I
      stage); 0.712<=R<0.770 indicates that the liver is in the intermediate state of
      compensated cirrhosis and decompensated cirrhosis (SFLI I+ stage); 0.629<=R<0.712
      indicates that the liver is in the decompensated cirrhosis stage with ascites
      (SFLI II stage); 0.401<=R<0.629 indicates that the liver is in the stage of
      severely decompensated cirrhosis with ascites, and patients present with varying
      degrees of hepatic encephalopathy, hepatic coma, and other complications.
      CONCLUSION: The SFLI that we constructed can sensitively and accurately reflect
      the conditions of liver cirrhosis damage and liver functional reserve.

PMID- 24284371
TI  - Evaluating the therapeutic effect of hepatocellular carcinoma treated with
      transcatheter arterial chemoembolization by magnetic resonance perfusion imaging.
AB  - PURPOSE: To compare the characteristics of magnetic resonance perfusion-weighted
      imaging (MRPWI) scans before and after transcatheter arterial chemoembolization
      (TACE) treatment of hepatocellular carcinoma (HCC) and to apply MRPWI in
      evaluating the therapeutic effect of TACE and prognosis of HCC. MATERIALS AND
      METHODS: Thirty-five patients with HCC undergoing their first TACE treatment were
      enrolled in this study. T2WI, T1WI, and PWI of MRI were performed 24-48 h before
      TACE and 48-168 h after TACE. Perfusion parameters calculated with the maximum
      slope were used to create a time-signal intensity curve (TSC). The efficacy of
      TACE treatment in HCC was evaluated by examining the hemodynamic changes in TSC
      caused by TACE treatment. RESULTS: TSC before TACE showed a pattern of a quick
      decrease and a slow increase in the tumor region of interest in 34 patients with
      HCC, whereas the TSC for normal liver tissues showed a pattern of slow decrease
      and slow increase. After TACE, the fluctuating range of TSC was significantly
      reduced in 31 patients, slightly reduced in three, and did not change
      significantly in one. The 3-year survival rate was 28.6%. CONCLUSION: MRPWI of
      the liver does not only show the anatomy of HCC lesions but also reflects
      hemodynamic changes of HCC before and after TACE to a certain extent. It is very
      useful for clinical evaluation of the efficacy of TACE for HCC.

PMID- 24284372
TI  - Epithelial-to-mesenchymal transition in a fistula-associated anal adenocarcinoma
      in a patient with long-standing Crohn's disease.
AB  - Anal adenocarcinomas arising from perianal fistulae represent a rare complication
      in Crohn's disease (CD) patients. We have previously demonstrated the involvement
      of an epithelial-to-mesenchymal transition (EMT) in the pathogenesis of CD
      associated fistulae. Although EMT has also been implicated in the development of
      colorectal and anal carcinoma, the molecular link from fistula to carcinoma is
      unclear. We present a case of a 48-year-old White woman who developed a mucinous
      anal adenocarcinoma originating from a perianal, CD-associated fistula 24 years
      after being diagnosed with CD. To characterize the expression of EMT-associated
      molecules in fistula and carcinoma tissue, immunohistochemical analysis for
      Snail1, Slug, beta-catenin and E-cadherin was performed. A mucinous anal
      adenocarcinoma developed on a perianal fistula in a patient with long-standing
      CD. After neoadjuvant radiochemotherapy, the fistula-associated tumour was
      resected and the patient is presently in remission. Using immunohistochemical
      analysis, we detected a remarkable staining of the Slug transcription factor in
      transitional cells lining the fistula tract. This observation is unique to this
      'carcinoma'-fistula: we had previously shown Slug expression in cells surrounding
      the fistula tract but not in transitional cells. Expression of Snail1, beta
      catenin and E-cadherin in this case was comparable with our previous findings. We
      describe a rare case of a CD fistula-associated adenocarcinoma within an area of
      squamous epithelium of the perianal area and an unusual expression pattern of EMT
      markers in this fistula. This case seems to underline the relevance of our
      previous findings demonstrating that EMT plays an important role for fistula
      pathogenesis and likely carcinogenesis in CD patients. 

PMID- 24284373
TI  - Combined use of metallic endoclips and endoloops using a single-channel scope in
      closing iatrogenic perforations and fistulas: two case reports and a literature
      review.
AB  - Iatrogenic perforation of the gastrointestinal tract is a rare complication of
      endoscopic procedures, whereas anastomotic leakage after surgery is not uncommon.
      Both conditions are associated with gut wall defects leading to significant
      morbidity and mortality of the patients. We describe two case reports, a colonic
      perforation and an esophagogastric anastomosis leakage successfully managed
      endoscopically using the combined technique with endoclips and endoloops. A
      literature review is performed on similar endoscopic techniques aiming to avoid
      surgical treatment in these patients. 

PMID- 24284374
TI  - Cancer stage and local immune response.

PMID- 24284375
TI  - Environments of B cell development.
AB  - B lymphocyte development in the mouse begins with the generation of long-term
      reconstituting, pluripotent hematopoietic stem cells, over multipotent
      myeloid/lymphoid progenitors and common lymphoid progenitors to B-lineage
      committed pro/pre B and pre B cells, which first express pre B cell receptors and
      then immunoglobulins, B cell receptors, to generate the repertoires of peripheral
      B cells. This development is influenced and guided by cells of non-hematopoietic
      and hematopoietic origins. We review here some of the recent developments, and
      our contributions in this fascinating field of developmental immunology. 

PMID- 24284376
TI  - Urinary fractalkine and monocyte chemoattractant protein-1 as possible predictors
      of disease activity of childhood glomerulonephritis.
AB  - Renal biopsy is the gold standard for confirmation of disease severity and
      diagnosis of glomerulonephritis (GN), but its procedure is invasive with a risk
      of complications. Thus, a non-invasive monitoring method is desirable especially
      in pediatric patients. Fractalkine and monocyte chemoattractant protein-1 (MCP-1)
      are proinflammatory chemokines, and both have been reported to be involved in the
      pathogenesis of immunocomplex-mediated GN. Recently, it has been reported that
      urinary fractalkine and MCP-1 may serve as possible predictors of disease
      activity of adult patients with GN. We, therefore, examined whether urinary
      levels of fractalkine and MCP-1 correlate with clinical and histologic
      parameters. Twenty-six consecutive children with various types of GN were
      enrolled in this study, including lupus nephritis, IgA nephropathy, membranous
      nephropathy, acute GN, and thin basement membrane disease (served as a non
      inflammatory control). Urinary fractalkine and MCP-1 concentrations in the first
      morning urine samples obtained at the time of renal biopsy were measured by
      enzyme-linked immunosorbent assay, and standardized for urinary creatinine
      concentrations. Urinary fractalkine concentration differed significantly among
      the disease categories. Urinary concentrations of fractalkine and MCP-1 showed a
      significant positive correlation with the degree of occult blood in urine and a
      significant inverse correlation with the estimated glomerular filtration rate.
      Furthermore, the urinary MCP-1 concentration was significantly correlated with
      histological chronicity indices in patients with lupus nephritis and IgA
      nephropathy. Measurement of urinary fractalkine and MCP-1 concentrations may be
      useful as a non-invasive method for predicting the disease activity of GN in
      children. 

PMID- 24284377
TI  - The 'beyond parental control' label in Nigeria.
AB  - Recent reports in Nigeria indicate a geometric rise in incarcerated adolescents,
      with an overwhelming majority of this increase being attributed to adolescents
      being declared 'beyond parental control'. There is a nagging suspicion that the
      Nigerian juvenile justice system has over criminalised adolescents by declaring
      them 'beyond control' when behavioural problems have actually resulted from child
      abuse/neglect and family disruption. A study was undertaken in a juvenile justice
      institution in Nigeria to assess the adequacy of pre-incarceration parental care
      among adolescents that had been declared as 'beyond parental control'. The study
      included 75 adolescent boys that had been declared as 'beyond parental control'
      and a comparison group of 144 matched school going boys. It examined self-reports
      received from the adolescent boys regarding their pre-incarceration family life
      and social circumstances, as well as the behavioural problems they had
      experienced. The findings indicate that adolescent boys who were declared as
      'beyond parental control' had a significantly higher lifetime history of
      behavioural problems than the comparison group, and they also had significantly
      higher indicators of pre-incarceration child abuse/neglect and problems with
      stability and consistency of primary support. These findings pose questions
      regarding the presumption of adequate parental care prior to the declaration of
      'beyond parental control'. It also raises questions about child rights protection
      and juvenile justice reform in Nigeria. 

PMID- 24284378
TI  - Tuning, inhibiting and restoring the enzyme mimetic activities of Pt-apoferritin.
AB  - A selective and specific inhibition of the catalase mimetic activity but not SOD
      like activity of Pt-apoferritin can be achieved through the choice of the
      inhibitor. The recovery of activity using a reducing agent was explored and
      proven to successfully restore the surface-chemistry of NPs. 

PMID- 24284379
TI  - The Prevalence of Metabolic Syndrome Among Soldiers of the Military Police of
      Bahia State, Brazil.
AB  - The mortality rate of men is generally higher than that of women, irrespective of
      the age group. Currently, a key concern for health care professionals is the
      prevalence of risk factors associated with cardiovascular disease and metabolic
      syndrome. This study aimed at assessing the prevalence of individual risk factors
      for cardiovascular disease as well as the prevalence of metabolic syndrome among
      men serving in the Military Police Corps of the state of Bahia, Brazil. This
      service employs mostly men, and they are known to experience high levels of
      occupational stress and professional victimization. We conducted a cross
      sectional study among military police soldiers (n = 452) who were candidates for
      a military police training course in Bahia, Brazil. All candidates who attended
      the selection process were evaluated according to the criteria of the National
      Cholesterol Education Program's Adult Panel III in order to assess the presence
      of medical disorders that could contribute to cardiovascular disease and
      metabolic syndrome. The authors identified a high prevalence of hypertension
      (55.76%), hypertriglyceridemia (50.85%), waist circumference of >102 cm (31.76%),
      low high-density lipoprotein cholesterol levels (30.46%), and impaired fasting
      glucose (28.15%) in our subjects. The overall prevalence of metabolic syndrome
      was 38.54%. The authors suggest that measures should be taken to ensure that
      military policemen receive continued medical care, both in their professional
      capacity and in their personal circumstances, and that attention be focused on
      intervention programs. 

PMID- 24284380
TI  - Large-area, continuous roll-to-roll nanoimprinting with PFPE composite molds.
AB  - Successful implementation of a high-speed roll-to-roll nanoimprinting technique
      for continuous manufacturing of electronic devices has been hindered due to lack
      of simple substrate preparation steps, as well as lack of durable and long
      lasting molds that can faithfully replicate nanofeatures with high fidelity over
      hundreds of imprinting cycles. In this work, we demonstrate large-area high-speed
      continuous roll-to-roll nanoimprinting of 1D and 2D micron to sub-100 nm features
      on flexible substrate using perfluoropolyether (PFPE) composite molds on a custom
      designed roll-to-roll nanoimprinter. The efficiency and reliability of the PFPE
      based mold for the dynamic roll-to-roll patterning process was investigated. The
      PFPE composite mold replicated nanofeatures with high fidelity and maintained
      superb mold performance in terms of dimensional integrity of the nanofeatures,
      nearly defect free pattern transfer and exceptional mold recovering capability
      throughout hundreds of imprinting cycles. 

PMID- 24284381
TI  - Chronic distress and acute vascular stress responses associated with ambulatory
      blood pressure in low-testosterone African men: the SABPA Study.
AB  - It is known that low testosterone (T) and high cortisol levels are associated
      with hypertension as well as with chronic stress, linking stress with elevated
      blood pressure (BP). However, the association between acute stress-, chronic
      stress responses and BP is not clear in Africans. Therefore, we examined the
      association between cortisol, psychological distress and BP responses in low- and
      high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and
      electrocardiogram measures were obtained. Serum samples were collected and
      analyzed for sex hormones and cortisol. Chronic psychological distress was
      verified with the General Health Questionnaire and acute stress with the cold
      pressor test. More chronic psychological distress was observed in both low- and
      high-T Africans compared with the Caucasians. The low-T Africans tended to have
      more ischemic events (P=0.06) and ABPM values (P?0.01) than any of the other
      groups. Both chronic distress (cortisol) and acute stress (total peripheral
      resistance cold pressor responses) were associated with ABPM in the low-T African
      group. Acute and chronic stress may contribute to increased BP in low-T African
      men. Their cortisol and vascular responses supported a tendency for ischemia,
      increasing their risk for coronary artery disease. 

PMID- 24284382
TI  - A marked proportional rise in IVC aldosterone following cosyntropin
      administration during AVS is a signal to the presence of adrenal hyperplasia in
      primary aldosteronism.
AB  - We hypothesized aldosteronoma responsiveness to cosyntropin may be a
      characterizing feature that could be determined in addition to standard adrenal
      vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October
      2011 including 65 patients with confirmed primary aldosteronism (PA) who
      underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided
      into confirmed lateralized and non-lateralized groups and subgrouped by
      histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post
      cosyntropin infusion during AVS was measured. Peak aldosterone and proportional
      change was compared between groups. Baseline and peak IVC aldosterone was higher
      in lateralized patients but incremental aldosterone rise was much greater in
      subjects with bilateral hyperplasia. From receiver operator characteristics (ROC)
      analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol
      l(-1) would have a sensitivity of 94% for surgical disease although specificity
      of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be
      specific enough to exclude 87% of surgical/lateralized disease. These diagnostic
      capabilities are similar to other results with non-AVS tests performed for
      diagnosis of lateralization. Although not specific enough to replace standard AVS
      interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is
      a useful additional test to diagnose non-lateralizing forms of PA. Such a
      calculation requires no additional expense or tests.

PMID- 24284383
TI  - Cardiovascular changes in children with coarctation of the aorta treated by
      endovascular stenting.
AB  - The aim of this study was to investigate the echocardiographic, biochemical short
      and mid-term effects of the stenting procedure on left ventricular function,
      aortic stiffness, elasticity and systemic hypertension in children with
      coarctation of the aorta (CoA). Fifteen patients with native or recurrent CoA and
      30 healthy controls who were sex and age matched were included in the study. The
      blood pressure values, echocardiographic measurements, elastic functions of
      ascending aorta and serum N-Terminal ProBNP (NT-ProBNP) levels were recorded
      prospectively before and at the first and sixth month after stenting. The mean
      arterial pressure recorded before stenting was 134.4+/-16.3 mm Hg; at the sixth
      month it was 115.5+/-9.5 mm Hg and in the control group it was 107.3+/-9.4 mm Hg.
      Although blood pressure levels were lower compared with the pre-stenting
      measurements (P<0.05), they were still significantly higher compared with the
      control group (P<0.05). Although a significant reduction was detected in the
      LVMIz at the end of the sixth month (50.4+/-14.3 g m(-2.7)) compared with the
      baseline (66.6+/-17.9 g m(-2.7); P<0.05), it was still higher compared with the
      control group (35.7+/-6.2 g m(-2.7); P<0.05). The baseline aortic elasticity
      (6.4+/-3.4 cm(2) dyn(-1) 10(-6)) was lower compared with the control group
      (10.0+/-1.7 cm(2) dyn(-1) 10(-6); P<0.05), and prestenting aortic stiffness was
      higher than that of the control group (5.6+/-1.6 dyn(-1) 10(-6); 2.5+/-0.45  dyn(
      1) 10(-6); P<0.05). A statistically significant negative correlation was detected
      between the pressure gradient at the lesion site and aortic elasticity (r: -0.53,
      P: 0.04). Although resolution of the coarctation by endovascular stenting led to
      a reduction in the arteriopathy that had already begun before treatment, it was
      demonstrated that these children did not completely return to normal. 

PMID- 24284384
TI  - Deregulation of adipokines related to target organ damage on resistant
      hypertension.
AB  - Resistant hypertension (RHTN) includes patients with controlled blood pressure
      (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely
      to have target organ damage (TOD), and resistin, leptin and adiponectin may
      affect BP control in these subjects. We assessed the relationship between
      adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and
      microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and
      UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure
      monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave
      velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher
      in UCRHTN, whereas adiponectin levels were lower in this same subgroup.
      Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup.
      Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=
      0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37,
      P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both
      subgroups. Adiponectin is associated with arterial stiffness and renal injury in
      UCRHTN patients, whereas leptin is associated with arterial stiffness in the same
      subgroup. Taken together, our results showed that those adipokines may contribute
      to vascular and renal damage in UCRHTN patients. 

PMID- 24284385
TI  - Pleiotropic effects of the acute and chronic inhibition of the renin-angiotensin
      system in hypertensives.
AB  - Renin-angiotensin system (RAS) inhibition may exert beneficiary pleiotropic
      effects on heart hemodynamics in hypertensive patients. We aimed to assess these
      effects on coronary flow reserve (CFR) and left ventricular (LV) filling pressure
      after acute and long-term treatment. Thirty-nine patients (48.4+/-6.8 years) with
      newly diagnosed, never-treated essential arterial hypertension were consecutively
      recruited from an outpatient hypertension clinic. CFR in the left anterior
      descending artery and the ratio of mitral inflow E wave to the averaged mitral
      annulus tissue velocity of the E waves (E/e' ratio), as an estimate of LV filling
      pressure, were assessed by Doppler echocardiography. In the acute phase of the
      study, consecutive eligible patients were assigned to receive po Quinapril (Q) 20
      mg (n=15) or Losartan (L) 100 mg (n=14) or no treatment (n=10) and were
      reexamined 2 h post treatment. In the chronic phase of the study, the patients
      were reevaluated after 1 month on the assigned treatment. During the acute phase,
      CFR (P=0.005) was significantly improved in the RAS inhibition as compared with
      the control group, independently of blood pressure (BP) changes. The E/e' ratio
      was also marginally improved (P=0.053), but this effect was more pronounced in
      patients with E/e' ratio>8 (P=0.005). CFR and E/e' ratio were also improved after
      1 month of treatment, particularly in responders after the acute phase. In
      hypertensive patients, RAS inhibition acutely improved CFR and E/e' ratio
      independently of BP changes. An acute positive response in these parameters was
      closely related to sustained improvement after 1 month of single-drug treatment. 

PMID- 24284386
TI  - Differential expression of vascular smooth muscle-modulating microRNAs in human
      peripheral blood mononuclear cells: novel targets in essential hypertension.
AB  - Vascular smooth muscle cell (VSMC) phenotypic plasticity has a critical role in
      the pathophysiology of arterial remodeling in essential hypertension. MicroRNAs
      are emerging as potential biomarkers and therapeutic targets in cardiovascular
      disease. We assessed the expression levels of the microRNAs miR-143, miR-145, miR
      21, miR-133 and miR-1, which are implicated in VSMC phenotypic modulation, in 60
      patients with essential hypertension and 29 healthy individuals. All patients
      underwent 24-h ambulatory blood pressure (BP) monitoring. MicroRNA levels in
      peripheral blood mononuclear cells were quantified by real-time reverse
      transcription polymerase chain reaction. Hypertensive patients showed lower miR
      143 (2.20+/-0.25 versus 4.19+/-0.57, P<0.001), miR-145 (13.51+/-1.73 versus
      22.38+/-3.31, P=0.010) and miR-133 (8.15+/-1.32 versus 37.03+/-8.18, P<0.001) and
      higher miR-21 (3.08+/-0.32 versus 2.06+/-0.31, P=0.048) and miR-1 (33.94+/-5.19
      versus 12.35+/-2.13 P=0.006) expression levels compared with controls. In
      hypertensive patients, we observed correlations of miR-143 (r = -0.380, P=0.003),
      miR-145 (r=-0.405, P=0.001), miR-21 (r=-0.486, P<0.001) and miR-133 (r=0.479,
      P<0.001) expression levels with 24-h diastolic BP. Furthermore, we observed
      correlations of miR-21 (r=-0.291, P=0.024), miR-1 (r=-0.312, P=0.015) and miR-133
      (r=0.310, P=0.016) levels with the dipping status. Associations of miR-143 (r=
      0.292, P=0.025), miR-145 (r=-0.399, P=0.002), miR-21 (r=-0.343, P=0.008) and miR
      133 (r=0.370, P=0.004) levels with 24-h mean pulse pressure were also found. Our
      data provide important evidence that VSMC-modulating microRNAs are closely
      related to essential hypertension in humans and they may represent potential
      therapeutic targets in essential hypertension.

PMID- 24284387
TI  - The impact of aerobic exercise on blood pressure variability.
AB  - There is increasing evidence that blood pressure variability (BPV, variation of
      blood pressure over time) constitutes a strong and independent marker of
      cardiovascular risk. The all-cause mortality is >50% greater in subjects with a
      standard deviation of inter-visit blood pressure >5 mm Hg. Regular aerobic
      exercise reduces blood pressure and is recommended by current hypertension
      guidelines as a basic lifestyle modification. It remains elusive, however,
      whether aerobic exercise is able to reduce BPV as well. In total, 72 hypertensive
      subjects were randomly assigned to an 8-12-week treadmill exercise program
      (target lactate 2.0+/-0.5 mmol l(-1)) or sedentary control. Blood pressure was
      measured by 24 h-ambulatory blood pressure monitoring (ABP). Two aspects of BPV
      were assessed: the variability of ABP and the variability of blood pressure on
      exertion. The coefficient of variation (CV) was used as a statistical measure of
      BPV. The CV of systolic daytime ABP was defined as primary outcome. The exercise
      program significantly decreased systolic and diastolic daytime ABP by 6.2+/-10.2
      mm Hg (P<0.01) and 3.0+/-6.3 mm Hg (P=0.04), respectively. Moreover, it reduced
      blood pressure on exertion and increased physical performance (P<0.05 each).
      Exercise had no impact, however, on the CV of daytime (10.2+/-2.7 vs. 9.8+/-2.6%,
      P=0.30) and night-time systolic (8.9+/-3.2 vs. 10.5+/-4.1%, P=0.10) and diastolic
      ABP (daytime 11.5+/-3.3 vs. 11.5+/-3.1%, night-time 12.0+/-4.3 vs. 13.8+/-5.2%;
      P>0.05 each). Regular aerobic exercise is a helpful adjunct to control blood
      pressure in hypertension, but it has no effect on 24 h- BPV, an independent
      predictor of cardiovascular risk. 

PMID- 24284388
TI  - Sustained protection against Ebola virus infection following treatment of
      infected nonhuman primates with ZMAb.
AB  - Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of
      up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV
      infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal
      antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The
      survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune
      responses. In order to evaluate whether the immune response induced in NHPs
      during the ZMAb treatment and EBOV challenge is sufficient to protect survivors
      against a subsequent exposure, animals that survived the initial challenge were
      rechallenged at 10 or 13 weeks after the initial challenge. The animals
      rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a
      rechallenge at 13 weeks. The data indicate that a robust immune response was
      generated during the successful treatment of EBOV-infected NHPs with EBOV, which
      resulted in sustained protection against a second lethal exposure. 

PMID- 24284389
TI  - Development and validation of a stability-indicating high performance liquid
      chromatographic (HPLC) method for the determination of related substances of
      micafungin sodium in drug substances.
AB  - An isocratic, sensitive and stability-indicating high performance liquid
      chromatographic (HPLC) method for separation and determination of the related
      substances of micafungin sodium was developed. The chromatographic separation was
      achieved on Agilent Zorbax SB-C18 column (250 * 4.6 mm, 5 MUm). Forced
      degradation study confirmed that the newly developed method was specific and
      selective to the degradation products. The performance of the method was
      validated according to the present ICH guidelines for specificity, linearity,
      accuracy, precision and robustness. Regression analysis showed correlation
      coefficient value greater than 0.999 for micafungin sodium and its six
      impurities. Limit of detection of impurities was in the range of 0.006%-0.013%
      indicating the high sensitivity of the newly developed method. Accuracy of the
      method was established based on the recovery obtained between 98.2% and 102.0%
      for all impurities. RSD obtained for the repeatability and intermediate precision
      experiments, was less than 1.0%. The method was successfully applied to quantify
      related substances of micafungin sodium in bulk drugs. 

PMID- 24284390
TI  - Kaempferol promotes apoptosis in human bladder cancer cells by inducing the tumor
      suppressor, PTEN.
AB  - Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and
      vegetables. Previous studies have identified Kae as a possible cancer preventive
      and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti
      migration effects in human bladder cancer EJ cells. Kaempferol robustly induced
      apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased
      cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to
      be associated with phosphatase and the tensin homolog deleted on the chromosome
      10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt
      phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown
      cells. Our findings indicate that Kae could be an alternative medicine for
      bladder cancer, based on a PTEN activation mechanism. 

PMID- 24284391
TI  - Bioactive constituents from "triguero" asparagus improve the plasma lipid profile
      and liver antioxidant status in hypercholesterolemic rats.
AB  - We have previously shown that the Andalusian-cultivated Asparagus officinalis L.
      "triguero" variety produces hypocholesterolemic and hepatoprotective effects on
      rats. This asparagus is a rich source of phytochemicals although we hypothesized
      there would be some of them more involved in these functional properties. Thus,
      we aimed to study the effects of asparagus (500 mg/kg body weight (bw)/day) and
      their partially purified fractions in flavonoids (50 mg/kg bw/day), saponins (5
      mg/kg bw/day) and dietary fiber (500 mg/kg bw/day) on oxidative status and on
      lipid profile in rats fed a cholesterol-rich diet. After 5 weeks treatment,
      plasma lipid values, hepatic enzyme activities and liver malondialdehyde (MDA)
      concentrations were measured. With the exception of the saponin fraction (SF),
      the administration of lyophilized asparagus (LA), fiber fraction (FF), and
      flavonoid fraction (FVF) to hypercholesterolemic rats produced a significant
      hypolipidemic effect compare to a high-cholesterol diet (HCD). In addition, the
      LA and FVF groups exhibited a significant increase in enzyme activity from
      multiple hepatic antioxidant systems including: superoxide dismutase, catalase,
      and gluthatione reductase/peroxidase as well as a decrease in MDA concentrations
      compared to HCD group. These results demonstrate that "triguero" asparagus
      possesses bioactive constituents, especially dietary fiber and flavonoids, that
      improve the plasma lipid profile and prevent hepatic oxidative damage under
      conditions of hypercholesterolemia. 

PMID- 24284392
TI  - Lessons from mouse models of high-fat diet-induced NAFLD.
AB  - Nonalcoholic fatty liver disease (NAFLD) encompasses a clinicopathologic spectrum
      of diseases ranging from isolated hepatic steatosis to nonalcoholic
      steatohepatitis (NASH), the more aggressive form of fatty liver disease that may
      progress to cirrhosis and cirrhosis-related complications, including
      hepatocellular carcinoma. The prevalence of NAFLD, including NASH, is also
      increasing in parallel with the growing epidemics of obesity and diabetes.
      However, the causal relationships between obesity and/or diabetes and NASH or
      liver tumorigenesis have not yet been clearly elucidated. Animal models of
      NAFLD/NASH provide crucial information, not only for elucidating the pathogenesis
      of NAFLD/NASH, but also for examining therapeutic effects of various agents. A
      high-fat diet is widely used to produce hepatic steatosis and NASH in
      experimental animals. Several studies, including our own, have shown that long
      term high-fat diet loading, which can induce obesity and insulin resistance, can
      also induce NASH and liver tumorigenesis in C57BL/6J mice. In this article, we
      discuss the pathophysiology of and treatment strategies for NAFLD and subsequent
      NAFLD-related complications such as NASH and liver tumorigenesis, mainly based on
      lessons learned from mouse models of high-fat diet-induced NAFLD/NASH. 

PMID- 24284393
TI  - The role of crowded physiological environments in prion and prion-like protein
      aggregation.
AB  - Prion diseases and prion-like protein misfolding diseases are related to the
      accumulation of abnormal aggregates of the normal host proteins including prion
      proteins and Tau protein. These proteins possess self-templating and
      transmissible characteristics. The crowded physiological environments where the
      aggregation of these amyloidogenic proteins takes place can be imitated in vitro
      by the addition of macromolecular crowding agents such as inert polysaccharides.
      In this review, we summarize the aggregation of prion proteins in crowded
      physiological environments and discuss the role of macromolecular crowding in
      prion protein aggregation. We also summarize the aggregation of prion-like
      proteins including human Tau protein, human alpha-synuclein, and human copper,
      zinc superoxide dismutase under macromolecular crowding environments and discuss
      the role of macromolecular crowding in prion-like protein aggregation. The
      excluded-volume effects caused by macromolecular crowding could accelerate the
      aggregation of neurodegenerative disease-associated proteins while inhibiting the
      aggregation of the proteins that are not neurodegenerative disease-associated. 

PMID- 24284395
TI  - Combination BMSC and Niaspan treatment of stroke enhances white matter remodeling
      and synaptic protein expression in diabetic rats.
AB  - OBJECTIVE: White matter remodeling plays an important role in neurological
      recovery after stroke. Bone marrow stromal cells (BMSCs) and Niaspan, an agent
      which increases high density lipoprotein (HDL), each induces neurorestorative
      effects and promotes white matter remodeling after stroke in non-diabetic rats.
      In this study, we test whether combination of BMSCs with Niaspan induces an
      enhanced white matter remodeling in the ischemic brain of diabetic rats. RESEARCH
      DESIGN AND METHODS: Type-1 diabetes (T1DM) rats were subjected to transient
      middle cerebral artery occlusion (MCAo) and treated with or without BMSCs;
      Niaspan; and the combination of BMSCs + Niaspan daily for 14 days after MCAo.
      Immunostaining for white matter remodeling and synaptic protein expression
      including NG2; CNPase; BS (Bielschowsky silver); LFB (luxol fast blue);
      Synaptophysin and SMI-31 immunostaining were performed. RESULTS: BMSC monotherapy
      did not regulate NG2 and CNPase expression compared to T1DM control rats. Both,
      combination of BMSCs + Niaspan treatment, and Niaspan monotherapy significantly
      increase NG2 and CNPase expression compared to T1DM control. While combination
      BMSC+Niaspan, BMSC monotherapy and Niaspan monotherapy groups all increase BS,
      LFB, synaptophysin, and SMI-31 expression in the ischemic brain compared to T1DM
      MCAo control. In addition, the combination treatment significantly enhances LFB,
      SMI-31, and Synaptophysin expression compared to BMSC monotherapy. CONCLUSIONS:
      Combination treatment of stroke with BMSCs and Niaspan in T1DM rats increases
      white matter remodeling and additively increases BMSC monotherapy induced
      myelination and synaptic plasticity after stroke in T1DM rats.

PMID- 24284394
TI  - MicroRNAs and triple negative breast cancer.
AB  - Triple Negative Breast Cancer (TNBC) is a very aggressive tumor subtype, which
      still lacks specific markers for an effective targeted therapy. Despite the
      common feature of negativity for the three most relevant receptors (ER, PgR and
      HER2), TNBC is a very heterogeneous disease where different subgroups can be
      recognized, and both gene and microRNA profiling studies have recently been
      carried out to dissect the different molecular entities. Moreover, several
      microRNAs playing a crucial role in triple negative breast cancer biology have
      been identified, providing the experimental basis for a possible therapeutic
      application. Indeed, the causal involvement of microRNAs in breast cancer and the
      possible use of these small noncoding RNA molecules as biomarkers has been
      extensively studied with promising results. Their application as therapeutic
      tools might represent an innovative approach, especially for a tumor subgroup
      still lacking an efficient and specific therapy such as TNBC. In this review, we
      summarize our knowledge on the most important microRNAs described in TNBC. 

PMID- 24284396
TI  - Galectin-1 is an interactive protein of selenoprotein M in the brain.
AB  - Selenium, an essential trace element for human health, mainly exerts its
      biological function through selenoproteins. Selenoprotein M (SelM) is one of the
      highly expressed selenoproteins in the brain, but its biological effect and
      molecular mechanism remain unclear. Thus, the interactive protein of SelM was
      investigated in this paper to guide further study. In order to avoid protein
      translational stop, the selenocysteine-encoding UGA inside the open reading frame
      of SelM was site-directly changed to the cysteine-encoding UGC to generate the
      SelM' mutant. Meanwhile, its N terminal transmembrane signal peptide was also cut
      off. This truncated SelM' was used to screen a human fetal brain cDNA library by
      the yeast two-hybrid system. A new interactive protein of SelM' was found to be
      galectin-1 (Gal-1). This protein-protein interaction was further verified by the
      results of fluorescence resonance energy transfer techniques, glutathione S
      transferase pull-down and co-immunoprecipitation assays. As Gal-1 plays important
      roles in preventing neurodegeneration and promoting neuroprotection in the brain,
      the interaction between SelM' and Gal-1 displays a new direction for studying the
      biological function of SelM in the human brain. 

PMID- 24284397
TI  - Enhancing metagenomics investigations of microbial interactions with biofilm
      technology.
AB  - Investigations of microbial ecology and diversity have been greatly enhanced by
      the application of culture-independent techniques. One such approach,
      metagenomics, involves sample collections from soil, water, and other
      environments. Extracted nucleic acids from bulk environmental samples are
      sequenced and analyzed, which allows microbial interactions to be inferred on the
      basis of bioinformatics calculations. In most environments, microbial
      interactions occur predominately in surface-adherent, biofilm communities. In
      this review, we address metagenomics sampling and biofilm biology, and propose an
      experimental strategy whereby the resolving power of metagenomics can be enhanced
      by incorporating a biofilm-enrichment step during sample acquisition. 

PMID- 24284398
TI  - Oxidative stress/angiotensinogen/renin-angiotensin system axis in patients with
      diabetic nephropathy.
AB  - Although recent studies have proven that renin-angiotensin system (RAS) blockades
      retard the progression of diabetic nephropathy, the detailed mechanisms of their
      reno-protective effects on the development of diabetic nephropathy remain
      uncertain. In rodent models, it has been reported that reactive oxygen species
      (ROS) are important for intrarenal angiotensinogen (AGT) augmentation in the
      progression of diabetic nephropathy. However, no direct evidence is available to
      demonstrate that AGT expression is enhanced in the kidneys of patients with
      diabetes. To examine whether the expression levels of ROS- and RAS-related
      factors in kidneys are increased with the progression of diabetic nephropathy,
      biopsied samples from 8 controls and 27 patients with type 2 diabetes were used.
      After the biopsy, these patients were diagnosed with minor glomerular abnormality
      or diabetes mellitus by clinical and pathological findings. The intensities of
      AGT, angiotensin II (Ang II), 4-hydroxy-2-nonenal (4-HNE), and heme oxygenase-1
      (HO-1) were examined by fluorescence in situ hybridization and/or
      immunohistochemistry. Expression levels were greater in patients with diabetes
      than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression
      paralleled renal dysfunction in patients with diabetes. These data suggest the
      importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of
      diabetic nephropathy. 

PMID- 24284399
TI  - Nutraceuticals: potential for chondroprotection and molecular targeting of
      osteoarthritis.
AB  - Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult
      disability. There is no cure for OA, and no effective treatments which arrest or
      slow its progression. Current pharmacologic treatments such as analgesics may
      improve pain relief but do not alter OA disease progression. Prolonged
      consumption of these drugs can result in severe adverse effects. Given the nature
      of OA, life-long treatment will likely be required to arrest or slow its
      progression. Consequently, there is an urgent need for OA disease-modifying
      therapies which also improve symptoms and are safe for clinical use over long
      periods of time. Nutraceuticals-food or food products that provide medical or
      health benefits, including the prevention and/or treatment of a disease-offer not
      only favorable safety profiles, but may exert disease- and symptom-modification
      effects in OA. Forty-seven percent of OA patients use alternative medications,
      including nutraceuticals. This review will overview the efficacy and mechanism of
      action of commonly used nutraceuticals, discuss recent experimental and clinical
      data on the effects of select nutraceuticals, such as phytoflavonoids,
      polyphenols, and bioflavonoids on OA, and highlight their known molecular actions
      and limitations of their current use. We will conclude with a proposed novel
      nutraceutical-based molecular targeting strategy for chondroprotection and OA
      treatment. 

PMID- 24284400
TI  - Let-7 in cardiovascular diseases, heart development and cardiovascular
      differentiation from stem cells.
AB  - The let-7 family is the second microRNA found in C. elegans. Recent researches
      have found it is highly expressed in the cardiovascular system. Studies have
      revealed the aberrant expression of let-7 members in cardiovascular diseases,
      such as heart hypertrophy, cardiac fibrosis, dilated cardiomyopathy (DCM),
      myocardial infarction (MI), arrhythmia, angiogenesis, atherosclerosis, and
      hypertension. Let-7 also participates in cardiovascular differentiation of
      embryonic stem cells. TLR4, LOX-1, Bcl-xl and AGO1 are by now the identified
      target genes of let-7. The circulating let-7b is suspected to be the biomarker of
      acute MI and let-7i, the biomarker of DCM. Further studies are necessary for
      identifying the gene targets and signaling pathways of let-7 in cardiovascular
      diseases. Let-7 might be a potential therapeutic target for cardiovascular
      diseases. This review focuses on the research progresses regarding the roles of
      let-7 in cardiovascular development and diseases. 

PMID- 24284402
TI  - GC and GC/MS analysis of essential oil composition of the endemic Soqotraen
      Leucas virgata Balf.f. and its antimicrobial and antioxidant activities.
AB  - Leucas virgata Balf.f. (Lamiaceae) was collected from the Island Soqotra (Yemen)
      and its essential oil was obtained by hydrodistillation. The chemical composition
      of the oil was investigated by GC and GC-MS. Moreover, the essential oil was
      evaluated for its antimicrobial activity against two Gram-positive bacteria, two
      Gram-negative bacteria, and one yeast species by using broth micro-dilution assay
      for minimum inhibitory concentrations (MIC) and antioxidant activity by measuring
      the scavenging activity of the DPPH radical. The investigation led to the
      identification of 43 constituents, representing 93.9% of the total oil. The
      essential oil of L. virgata was characterized by a high content of oxygenated
      monoterpenes (50.8%). Camphor (20.5%) exo-fenchol (3.4%), fenchon (5.4%), and
      borneol (3.1%) were identified as the main components. Oxygenated sesquiterpenes
      were found as the second major group of compounds (21.0%). beta-Eudesmol (6.1%)
      and caryophyllene oxide (5.1%) were the major compounds among oxygenated
      sesquiterpenes. The results of the antimicrobial assay showed that the oil
      exhibited a great antibacterial activity against the tested S. aureus, B.
      subtilis, and E. coli. No activity was found against P. aeruginosa and C.
      albicans. Moreover, the DPPH-radical scavenging assay exhibited only a moderate
      antioxidant activity (31%) for the oil at the highest concentration tested (1
      mg/mL). 

PMID- 24284403
TI  - Detection of lymph node metastases in human colorectal cancer by using 5
      aminolevulinic acid-induced protoporphyrin IX fluorescence with spectral
      unmixing.
AB  - Accurate evaluation of metastatic lymph nodes (LNs) is indispensable for adequate
      treatment of colorectal cancer (CRC) patients. Here, we demonstrate detection of
      metastases of human CRC in removed fresh LNs using 5-aminolevulinic acid (ALA)
      induced protoporphyrin IX (PpIX) fluorescence. A spectral unmixing method was
      employed to reduce the overlap of collagen autofluorescence on PpIX fluorescence.
      A total of 17 surgery patients with advanced CRC were included in this study.
      After 5-ALA at a dose of 15 mg/kg of body weight was applied orally 2 h prior to
      surgery, 87 LNs were subjected to spectral fluorescence imaging and
      histopathological diagnosis, and statistical analysis was performed. No apparent
      side effect was observed to be associated with 5-ALA administration. The spectral
      unmixing fluorescence intensity of PpIX in metastatic LNs was 10.2-fold greater
      than that in nonmetastaic LNs. The receiver-operating-characteristic (ROC)
      analysis showed that the area under the curve (AUC) was calculated as 0.95. Our
      results show the potential of 5-ALA-induced PpIX fluorescence processed by
      spectral unmixing for detecting metastases in excised fresh LNs from patients
      with CRC, suggesting that this rapid and feasible method is applicable to gross
      evaluation of resected LN samples in pathology laboratories. 

PMID- 24284401
TI  - Oxidative stress mechanisms underlying Parkinson's disease-associated
      neurodegeneration in C. elegans.
AB  - Oxidative stress is thought to play a significant role in the development and
      progression of neurodegenerative diseases. Although it is currently considered a
      hallmark of such processes, the interweaving of a multitude of signaling cascades
      hinders complete understanding of the direct role of oxidative stress in
      neurodegeneration. In addition to its extensive use as an aging model, some
      researchers have turned to the invertebrate model Caenorhabditis elegans (C.
      elegans) in order to further investigate molecular mediators that either
      exacerbate or protect against reactive oxygen species (ROS)-mediated
      neurodegeneration. Due to their fully characterized genome and short life cycle,
      rapid generation of C. elegans genetic models can be useful to study upstream
      markers of oxidative stress within interconnected signaling pathways. This report
      will focus on the roles of C. elegans homologs for the oxidative stress
      associated transcription factor Nrf2, as well as the autosomal recessive, early
      onset Parkinson's disease (PD)-associated proteins Parkin, DJ-1, and PINK1, in
      neurodegenerative processes. 

PMID- 24284404
TI  - Tetra-repeat microsatellite markers for the masu salmon (Oncorhynchus masou
      masou) and its application in cross-subspecies amplification.
AB  - We developed tetranucleotide-repeat microsatellite markers for the masu salmon
      (Oncorhynchus masou) complex. 454 pyrosequencing was used to discover repeat
      motifs, and seven polymorphic microsatellite-primer sets were identified. The
      number of alleles detected at each locus ranged from four to 24 and the expected
      heterozygosity varied from 0.57 to 0.92. Cross-subspecies amplification for O. m.
      masou, O. m. ishikawae and O. m. subsp. was successful. These microsatellites can
      be utilized in studies of genetic structure, genetic diversity, and intra- and
      inter-subspecific hybridization, making a contribution to conservation and
      management of the Oncorhynchus masou complex. 

PMID- 24284405
TI  - Systems biology approach to the dissection of the complexity of regulatory
      networks in the S. scrofa cardiocirculatory system.
AB  - Genome-wide experiments are routinely used to increase the understanding of the
      biological processes involved in the development and maintenance of a variety of
      pathologies. Although the technical feasibility of this type of experiment has
      improved in recent years, data analysis remains challenging. In this context,
      gene set analysis has emerged as a fundamental tool for the interpretation of the
      results. Here, we review strategies used in the gene set approach, and using
      datasets for the pig cardiocirculatory system as a case study, we demonstrate how
      the use of a combination of these strategies can enhance the interpretation of
      results. Gene set analyses are able to distinguish vessels from the heart and
      arteries from veins in a manner that is consistent with the different cellular
      composition of smooth muscle cells. By integrating microRNA elements in the
      regulatory circuits identified, we find that vessel specificity is maintained
      through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated
      expression with their mRNA targets. 

PMID- 24284406
TI  - Different effects of androgen on the expression of Fut1, Fut2, Fut4 and Fut9 in
      male mouse reproductive tract.
AB  - The alpha-(1,2) fucosyltransferases (Fut1 and Fut2) and alpha-(1,3)
      fucosyltransferases (Fut4, Fut9) are responsible for the synthesis of Lewis X
      (LeX) and Lewis Y (LeY) conjugated to glycoproteins. We recently reported that
      these fucosyltransferases were differentially expressed in the reproductive tract
      of male mouse. Here, we studied the effect of androgen on fucosyltransferase
      expression through the use of mouse castration models. We found that Fut1 mRNA
      and Fut4 mRNA were upregulated, while Fut2 mRNA and Fut9 mRNA were downregulated
      by androgen in the caput epididymis. However, in the vas deferens and prostate,
      only Fut4 mRNA and Fut2 mRNA were respectively upregulated following exposure to
      androgen. In the seminal vesicle, all fucosyltransferases, with the exception of
      Fut9, were upregulated. We identified the androgen receptor binding sites (ARBSs)
      of Fut2, Fut4 and Fut9 in the caput epididymis. Luciferase assay for these ARBSs
      is able to provide an indication as to why Fut4 and Fut9 are differently
      expressed and regulated by androgen, although they catalyze the same alpha-(1,3)
      fucose linkage. Our study showed that androgen could differentially regulate the
      expression of these fucosyltransferases and provided an insight into the
      characteristic distribution of each fucosyltransferase responsible for LeX/LeY
      biosynthesis in the male reproductive tract. 

PMID- 24284407
TI  - Possible role of -374T/A polymorphism of RAGE gene in longevity.
AB  - Demographic and social changes in the last decades have resulted in improvements
      in health and longevity. The survival of elderly people has improved
      significantly and thus centenarians are becoming the fastest growing population
      group. Environmental, genetic, and accidental factors have influenced the human
      life span. Researchers have gained substantial evidence that advanced glycation
      end products may play an important role in the processes of physiological aging.
      The aim of the present study was to investigate any differences in the
      frequencies of -374T/A polymorphism in subjects aged >90 years and in middle-aged
      individuals. We observed association between the A allele and genotype homozygous
      for this allele (AA) with a longer life expectancy in the male population. In
      particular, there was a prevalence of AA genotype and A allele in long-living
      subjects and a prevalence of the allele T in middle-aged subjects, indicating a
      possible protective role of the allele A to aging. In conclusion, our results
      support the hypothesis that longevity is the result of a good functioning of the
      immune system and a presumable hyper-expression of variants of anti-inflammatory
      genes of immunity. The differences in the genetic regulation of inflammatory
      processes may influence the presence of age-related disorders. 

PMID- 24284408
TI  - Exposure conditions and pharmacokinetic principles: interpreting bisphenol a
      absorption in the canine oral cavity.

PMID- 24284409
TI  - C. elegans sensing of and entrainment along obstacles require different neurons
      at different body locations.
AB  - We probe C. elegans mechanosensation using a microfabricated platform where worms
      encounter a linear array of asymmetric funnel-like barriers. We found that
      sensing of and moving along barriers require different sets of neurons located at
      different parts of the animal. Wild-type worms sense and move along the barrier
      walls, leading to their accumulation in one side of the barriers due to the
      barriers' asymmetric shape. However, mec-4 and mec-10 mutants deficient in touch
      sensory neurons in the body exhibited reversal movements at the walls, leading to
      no accumulation in either side of the barriers. In contrast, osm-9 mutants
      deficient in touch sensory neurons in the nose, moved along the barrier walls.
      Thus, touch sensory neurons ALM and AVM in the body are required for C. elegans
      to sense and move along obstacles, whereas the ASH and FLP neurons in the nose
      are required only for sensing of but not moving along obstacles. 

PMID- 24284410
TI  - A reduction in chronic hepatitis B virus infection prevalence among children in
      Vietnam demonstrates the importance of vaccination.
AB  - BACKGROUND: Vietnam has high endemic hepatitis B virus infection with >8% of
      adults estimated to have chronic infection. Hepatitis B vaccine was first
      introduced in the national childhood immunization program in 1997 in high-risk
      areas, expanded nationwide in 2002, and included birth dose vaccination in 2003.
      This survey aimed to assess the impact of Vietnam's vaccination programme by
      estimating the prevalence of hepatitis B surface antigen (HBsAg) among children
      born during 2000-2008. METHODS: This nationally representative cross-sectional
      survey sampled children based on a stratified three-stage cluster design.
      Demographic and vaccination data were collected along with a whole blood specimen
      that was collected and interpreted in the field with a point-of-care HBsAg test.
      RESULTS: A total of 6,949 children were included in the survey analyses. The
      overall HBsAg prevalence among surveyed children was 2.70% (95% confidence
      interval (CI): 2.20-3.30). However, HBsAg prevalence was significantly higher
      among children born in 2000-2003 (3.64%) compared to children born 2007-2008
      (1.64%) (prevalence ratio (PR: 2.22, CI 1.55-3.18)). Among all children included
      in the survey, unadjusted HBsAg prevalence among children with >=3 doses of
      hepatitis B vaccine including a birth dose (1.75%) was significantly lower than
      among children with >=3 doses of hepatitis B vaccine but lacked a birth dose
      (2.98%) (PR: 1.71, CI: 1.00-2.91) and significantly lower than among unvaccinated
      children (3.47%) (PR: 1.99, CI: 1.15-3.45). Infants receiving hepatitis B vaccine
      >7 days after birth had significantly higher HBsAg prevalence (3.20%) than those
      vaccinated 0-1 day after birth (1.52%) (PR: 2.09, CI: 1.27-3.46). CONCLUSION:
      Childhood chronic HBV infection prevalence has been markedly reduced in Vietnam
      due to vaccination. Further strengthening of timely birth dose vaccination will
      be important for reducing chronic HBV infection prevalence of under 5 children to
      <1%, a national and Western Pacific regional hepatitis B control goal.

PMID- 24284411
TI  - Vaccination for safe travel to India.
AB  - Worldwide more than 900 million international journeys are undertaken every year.
      India is one of the favorite tourist destinations around the world. International
      travel exposes travelers to a range of health risks. Traveling to India possess a
      threat to travelers with waterborne diseases like bacterial diarrhea, hepatitis A
      and E, and typhoid fever; vector borne diseases like dengue fever, Japanese
      encephalitis, and malaria; animal contact disease like rabies. Furthermore
      diseases spreading through behavior aspects cannot be ruled out hence posing a
      risk for hepatitis B, HIV/AIDS, hepatitis C as well. Hence, before travel the
      travelers are advised about the risk of disease in the country or countries they
      plan to visit and the steps to be taken to prevent illness. Vaccination offers
      the possibility of avoiding a number of infectious diseases that may be countered
      abroad. There is no single vaccination schedule that fits all travelers. Each
      schedule must be individualized according to the traveler's previous
      immunizations, countries to be visited, type and duration of travel, and the
      amount of time available before departure. 

PMID- 24284413
TI  - Efficacy of hepatitis A vaccination and factors impacting on seroconversion in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Little is known about the immune response to hepatitis A virus (HAV)
      vaccinations in patients with inflammatory bowel disease (IBD). We therefore
      assessed the immunogenicity of HAV vaccine in patients with IBD and evaluated the
      impact on vaccination efficacy of immunosuppressants, including corticosteroids,
      thiopurines, and anti-tumor necrosis factor (anti-TNF) agents. METHODS: This open
      prospective study evaluated the efficacy of HAV vaccination in 419 anti-HAV
      negative adult patients with IBD. Patients were vaccinated against HAV at 0 and 6
      to 12 months, with seroconversion (anti-HAV immunoglobulin G) measured 1 to 3
      months after the second dose. RESULTS: Of the 419 vaccinated patients who
      finished the study protocol (mean age, 26.9 yr), 355 (84.7%) had Crohn's disease
      and 64 (15.3%) had ulcerative colitis. The overall seroconversion rate was 97.6%
      (409/419) but was significantly lower in patients treated with the anti-TNF
      monoclonal antibody infliximab or adalimumab than in those not treated (92.4%
      [85/92] versus 99.1% [324/327], P = 0.001). In addition, the seroconversion rate
      was significantly lower in patients treated with >=2 than with <2
      immunosuppressants (92.6% [50/54] versus 98.4% [359/365], P = 0.03). When
      comparing anti-TNF alone with anti-TNF and other immunosuppressants, there was no
      significant difference in seroconversion rates (odds ratio, 1.2; 95% confidence
      interval, 0.2-5.6; P = 0.83). The sample/cutoff ratio was significantly lower in
      patients who did receive anti-TNF therapy than in those who did not (5.5 versus
      9.6; P < 0.001). CONCLUSIONS: Although HAV vaccination is generally effective in
      patients with IBD, the seroconversion rate is lower in patients receiving anti
      TNF agents (ClinicalTrials.gov registration number NCT01341808).

PMID- 24284412
TI  - Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics
      revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic
      reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain.
AB  - FE65 is a cytosolic adapter protein and an important binding partner of amyloid
      precursor protein. Dependent on Thr668 phosphorylation in amyloid precursor
      protein, which influences amyloidogenic amyloid precursor protein processing,
      FE65 undergoes nuclear translocation, thereby transmitting a signal from the cell
      membrane to the nucleus. As this translocation may be relevant in Alzheimer
      disease, and as FE65 consists of three protein-protein interaction domains able
      to bind and affect a variety of other proteins and downstream signaling pathways,
      the identification of the FE65 interactome is of central interest in Alzheimer
      disease research. In this study, we identified 121 proteins as new potential FE65
      interacting proteins in a pulldown/mass spectrometry approach using human post
      mortem brain samples as protein pools for recombinantly expressed FE65. Co
      immunoprecipitation assays further validated the interaction of FE65 with the
      candidates SV2A and SERCA2. In parallel, we investigated the whole cell proteome
      of primary hippocampal neurons from FE65/FE65L1 double knockout mice. Notably,
      the validated FE65 binding proteins were also found to be differentially abundant
      in neurons derived from the FE65 knockout mice relative to wild-type control
      neurons. SERCA2 is an important player in cellular calcium homeostasis, which was
      found to be up-regulated in double knockout neurons. Indeed, knock-down of FE65
      in HEK293T cells also evoked an elevated sensitivity to thapsigargin, a stressor
      specifically targeting the activity of SERCA2. Thus, our results suggest that
      FE65 is involved in the regulation of intracellular calcium homeostasis. Whereas
      transfection of FE65 alone caused a typical dot-like phenotype in the nucleus, co
      transfection of SV2A significantly reduced the percentage of FE65 dot-positive
      cells, pointing to a possible role for SV2A in the modulation of FE65
      intracellular targeting. Given that SV2A has a signaling function at the
      presynapse, its effect on FE65 intracellular localization suggests that the
      SV2A/FE65 interaction might play a role in synaptic signal transduction. 

PMID- 24284414
TI  - Electronic monitoring of medication adherence in a 1-year clinical study of 2
      dosing regimens of mesalazine for adults in remission with ulcerative colitis.
AB  - BACKGROUND: Adherence to medication is an issue of great importance for patients
      with ulcerative colitis. Once daily mesalazine seems to be no worse than divided
      doses in preventing relapse in remitting patients. Although this has been
      attributed to improved adherence, detailed measures of adherence have been
      lacking from previous studies. METHODS: A 1-year substudy was conducted alongside
      a trial that compared 2 different dosing regimens (once daily versus three times
      daily) of mesalazine for patients in remission with ulcerative colitis.
      Participants in the substudy had their adherence monitored electronically using
      the medication event monitoring system, self-report, and tablet counts. We
      compared measures, determined factors associated with adherence and associations
      between adherence and relapse, modeled adherence over time, and explored
      behavioral aspects. RESULTS: We included 58 participants. Adherence was high
      across all measures (89.3% self-report, 96.7% tablet counts, and 89.2% medication
      event monitoring system). Agreement between the measures was poor at times.
      Adherence according to the medication event monitoring system best distinguished
      between the participants who relapsed (71.4%) and those who remained in remission
      (93.4%), although this difference was not statistically discernible at the 5%
      level. Adherence deteriorated over the study period, with three times daily
      participants generally less adherent than once-daily participants (odds ratio,
      0.03; 95% confidence interval, 0.01-0.08). Adherence was higher on weekdays (odds
      ratio, 1.47; 95% confidence interval, 1.31-1.65) and around clinic visit dates
      (odds ratio, 1.43; 95% confidence interval, 1.18-1.72). CONCLUSIONS: Simple
      dosing regimens are preferable to multiple daily dosing regimens. Electronic
      monitoring of adherence should be used more often in clinical studies. Self
      reported adherence and tablet counts may underestimate adherence. Adherence
      declined over time, and adherence was generally lower and more varied for those
      allocated to the three times daily regimen.

PMID- 24284415
TI  - A systematic review of the evidence for central nervous system plasticity in
      animal models of inflammatory-mediated gastrointestinal pain.
AB  - BACKGROUND: Abdominal pain frequently accompanies inflammatory disorders of the
      gastrointestinal tract (GIT), and animal models of GIT inflammation have been
      developed to explore the role of the central nervous system (CNS) in this
      process. Here, we summarize the evidence from animal studies for CNS plasticity
      following GIT inflammation. METHODS: A systematic review was conducted to
      identify studies that: (1) used inflammation of GIT organs, (2) assessed pain or
      visceral hypersensitivity, and (3) presented evidence of CNS involvement. Two
      hundred and eight articles were identified, and 79 were eligible for analysis.
      RESULTS: Rats were most widely used (76%). Most studies used adult animals (42%)
      with a bias toward males (74%). Colitis was the most frequently used model (78%)
      and 2,4,6-trinitrobenzenesulfonic acid the preferred inflammatory agent (33%).
      Behavioral (58%), anatomical/molecular (44%), and physiological (24%) approaches
      were used alone or in combination to assess CNS involvement during or after GIT
      inflammation. Measurement times varied widely (<1 h-> 2 wk after inflammation).
      Blinded outcomes were used in 42% studies, randomization in 10%, and evidence of
      visceral inflammation in 54%. Only 3 studies fulfilled our criteria for high
      methodological quality, and no study reported sample size calculations.
      CONCLUSIONS: The included studies provide strong evidence for CNS plasticity
      following GIT inflammation, specifically in the spinal cord dorsal horn. This
      evidence includes altered visceromotor responses and indices of referred pain,
      elevated neural activation and peptide content, and increased neuronal
      excitability. This evidence supports continued use of this approach for
      preclinical studies; however, there is substantial scope to improve study design.

PMID- 24284416
TI  - Orexin as an input of circadian system in goldfish: Effects on clock gene
      expression and locomotor activity rhythms.
AB  - Orexins are neuropeptides mainly known for regulating feeding behavior and sleep
      wakefulness cycle in vertebrates. Daily variations of orexin-A expression have
      been reported in fish, with the highest levels preceding feeding time. However,
      it is unknown if such variations could be related with daily rhythms of clock
      genes, which form the molecular core of circadian oscillators. The aim of the
      present study was to identify the possible role of orexin as an input element of
      the goldfish circadian system. It was investigated the effects of orexin-A
      (10ng/gbw) intracerebroventricular injections on the expression of clock genes,
      NPY and ghrelin, as well as on daily locomotor activity rhythms. Goldfish held
      under 12L:12D photoperiod and injected at midday with orexin or saline, were
      sacrificed at 1 and 3h post-injection. The analysis of genes expression by qReal
      Time PCR showed an increment of Per genes in hypothalamus and foregut at 3h post
      injection, but not in hindgut and liver. The gBmal1a expression remained
      unaltered in all the studied tissues. Orexin induced NPY in the hypothalamus and
      ghrelin in the foregut. Locomotor activity was studied in fish daily injected
      with orexin for several consecutive days under different experimental conditions.
      Orexin synchronized locomotor activity in goldfish maintained in 24L and fasting
      conditions. Present results support a cross-talking between orexin-A and other
      feeding regulators at central and peripheral level, and suggest, for the first
      time, a role of this peptide as an input of the circadian system in fish. 

PMID- 24284417
TI  - Relationship between human cord blood adropin levels and fetal growth.
AB  - Adropin is a recently identified peptide and participates in the regulation of
      energy homeostasis and vascular function. The aim of this study was to examine
      the relationships between human cord blood adropin levels and fetal growth. A
      total of 159 newborns [preterm delivery (PTD), n=72; term delivery, n=87] were
      recruited. Adropin levels in cord blood were determined using enzyme-linked
      immunosorbent assay kits. Clinical information on fetal growth was collected.
      Adropin levels in PTD babies (median, 2028; 25th-75th, 1413-2484pg/ml) were lower
      than those in term delivery babies (median, 2305; 25th-75th, 1960-2684pg/ml,
      P=0.01). Birth weight and length z score, Ponderal index, placental length,
      breadth, thickness, surface area, volume and density were not significantly
      correlated to adropin concentrations in term delivery group. However, we found
      adropin concentrations were significantly correlated to gestational age at birth
      (Spearman's correlation coefficient=0.35, P<0.01) and placental weight
      (Spearman's correlation coefficient=0.24, P=0.04) in PTD group. We also found
      that boys had lower adropin levels than girls in PTD group (P=0.01). When the
      analysis was extended to the whole group (PTD and term deliveries combined), the
      results were similar to those for PTD group alone. After adjusting for maternal
      age and newborn's sex, every 100pg/ml increase of adropin concentration was
      significantly associated with a decreased risk of PTD (odds ratio, 0.95; 95%
      confidence interval, 0.91-0.99). Our study showed that cord blood adropin levels
      were positively correlated with gestational age and placental weight but not with
      other fetal growth parameters. 

PMID- 24284418
TI  - Use of hyposmia and other non-motor symptoms to distinguish between drug-induced
      parkinsonism and Parkinson's disease.
AB  - Drug-induced Parkinsonism (DIP) secondary to antipsychotics and other dopamine
      antagonists is common and can be clinically indistinguishable from idiopathic
      Parkinson's disease (PD). Making the correct diagnosis is essential as it has
      important implications both for management of the underlying psychiatric
      condition and potentially lifelong therapy with antiparkinsonian agents.
      Additionally, because Parkinsonism does not always resolve with withdrawal of the
      offending agent or can recur years later, DIP may sometimes represent unmasking
      of incipient PD. The problem is increasing in scope as antipsychotic drugs are
      prescribed for a widening variety of indications, and understanding the factors
      that distinguish pharmacologic from degenerative Parkinsonism represents a
      significant unmet need. In this review, we discuss the rationale and evidence for
      using pre-clinical manifestations of PD, particularly non-motor symptoms, to
      distinguish between the conditions. 

PMID- 24284419
TI  - The prevalence and odds of depressive symptoms and clinical depression in
      psoriasis patients: a systematic review and meta-analysis.
AB  - The reported prevalence of depression in psoriasis varies substantially. This
      study aims to determine the prevalence and odds of depressive symptoms and
      clinical depression in psoriasis. A systematic literature search was conducted.
      Mean questionnaire values and proportions for depressive symptoms and clinical
      depression were pooled according to different assessment methods. In controlled
      studies, standardized mean differences (SMDs) and odds ratio (OR) compared
      depression in psoriasis patients with controls using the random-effect model. The
      majority of the 98 eligible studies were conducted in tertiary centers without a
      control group. The prevalence of depressive symptoms was 28% using questionnaires
      and the prevalence of clinical depression was 12% using International
      Classification of Diseases codes, 19% using Diagnostic and Statistical Manual of
      Mental Disorders IV, and 9% for antidepressant use. Psoriasis patients had
      significantly more depressive symptoms (SMD 1.16; 95% confidence interval (CI)
      0.67-1.66), and population-based studies showed that they were at least one and a
      half times more likely to experience depression (OR 1.57; 95% CI 1.40-1.76) and
      used more antidepressants than did controls (OR 4.24, 95% CI 1.53-11.76). More
      than 10% of psoriasis patients suffer from clinical depression, and twice as many
      have depressive symptoms. The high prevalence of these symptoms is likely to be
      affected by the tertiary study populations and differential misclassification
      using questionnaires, where psoriasis-related symptoms may be detected as
      depressive symptoms. 

PMID- 24284420
TI  - FoxO3a is an antimelanogenic factor that mediates antioxidant-induced
      depigmentation.
AB  - Forkhead box-O (FoxO) family transcriptional factors control the expression of
      many genes involved in a variety of cellular processes. Melanogenesis is an
      oxidizing process; therefore, many antioxidants are used to inhibit melanin
      production. However, their mechanism of action is poorly understood. In this
      study, we investigated the role of FoxO3a, which is a key factor in oxidative
      stress-related cellular responses in melanogenesis. When FoxO3a expression was
      inhibited, the expression of melanogenic genes and melanin levels increased. In
      contrast, the overexpression of wild-type FoxO3a and the increased nuclear
      translocation induced by the phosphoinositide 3-kinase inhibitors or by Akt
      inhibition reversed these phenomena. This effect was not observed when FoxO3a
      harbored a deletion in the nuclear localization signal, indicating that its
      nuclear translocation is important for the regulation of melanogenesis. When
      antioxidants such as vitamin C, N-acetylcysteine, and Trolox were applied to MNT1
      cells, melanin levels decreased in parallel with FoxO3a nuclear translocation,
      and this effect disappeared with FoxO3a-directed small interfering RNA treatment.
      Because FoxO3a orchestrates the expression of many genes in order to regulate
      cellular phenotypes in a variety of environmental states, this gene, a factor
      involved in melanogenesis regulation, may represent a good target for studying
      antimelanogenic signaling pathways and for designing pharmacological or
      antimelanogenic agents that regulate melanin synthesis. 

PMID- 24284421
TI  - Downregulation of STRA6 expression in epidermal keratinocytes leads to
      hyperproliferation-associated differentiation in both in vitro and in vivo skin
      models.
AB  - Retinoids are known to affect skin cell proliferation and differentiation and are
      key molecules that target retinoid and retinoic acid receptors (RXRs and RARs),
      leading to physiological and pharmacologic effects. Our aim was to elucidate the
      role of the retinol-binding protein receptor STRA6, mediating cellular uptake of
      retinol, on skin structure and function. Our results indicate that STRA6 is
      constitutively expressed in human epidermal keratinocytes and dermal fibroblasts
      and is regulated via RAR/RXR-mediated pathways. HaCaT (Human adult low Calcium
      high Temperature) cells with stable STRA6 knockdown (STRA6KD) showed increased
      proliferation. Consistently, human organotypic 3D skin models using stable
      STRA6KD HaCaT cells showed a significantly thicker epidermis and enhanced
      expression of activation, differentiation, and proliferation markers. The effects
      were reversible after treatment with free retinol. Human skin reconstitution
      employing STRA6KD HaCaT cells leads to massive epithelial thickening under in
      vivo conditions in SCID mice. We propose that STRA6KD could lead to cellular
      vitamin A deficiency in keratinocytes. Consequently, STRA6 has a role for
      regulating retinoid homeostasis and in helping to program signaling that drives
      proliferation and differentiation of human skin cells. By its influence on
      hyperproliferation-associated differentiation, STRA6 could also have a role in
      skin regeneration and could be a target for pharmacological approaches to improve
      wound healing. 

PMID- 24284423
TI  - Isolation and structural characterization of a novel antioxidant mannoglucan from
      a marine bubble snail, Bullacta exarata (Philippi).
AB  - Bullacta exarata is one of the most economically important aquatic species in
      China, noted for not only its delicious taste and nutritional value, but also for
      its pharmacological activities. In order to explore its potential in medical
      applications, a mannoglucan designated as BEPS-IB was isolated and purified from
      the foot muscle of B. exarata after papain digestion. Chemical composition
      analysis indicated BEPS-IB contained mainly D-glucose and D-mannose in a molar
      ratio of 1:0.52, with an average molecular weight of about 94 kDa. The linkage
      information was determined by methylation analysis, and the anomeric
      configuration and chain linkage were confirmed by IR and 2D NMR. The results
      indicated BEPS-IB was composed of Glcp6Manp heptasaccharide repeating unit in the
      backbone, with occasional branch chains of mannose residues (14%) occurring in
      the backbone mannose. Further antioxidant assay indicated BEPS-IB exhibited
      positive antioxidant activity in scavenging superoxide radicals and reducing
      power. This is the first report on the structure and bioactivity of the
      mannoglucan from the B. exarata.

PMID- 24284422
TI  - Protein oxidation and DNA repair inhibition by 6-thioguanine and UVA radiation.
AB  - Damage to skin DNA by solar UV is largely unavoidable, and an optimal cellular
      response to it requires the coordinated operation of proteins in numerous
      pathways. A fully functional DNA repair proteome for removing harmful DNA lesions
      is a prerequisite for an appropriate DNA damage response. Genetically determined
      failure to repair UV-induced DNA damage is associated with skin photosensitivity
      and increased skin cancer risk. Patients treated with immunosuppressant/anti
      inflammatory thiopurines are also photosensitive and have high rates of sun
      related skin cancer. Their DNA contains the base analog 6-thioguanine (6-TG),
      which acts as a UVA photosensitizer to generate reactive oxygen species (ROS),
      predominantly singlet oxygen ((1)O2). ROS damage both DNA and proteins. Here we
      show that UVA irradiation of cultured human cells containing DNA 6-TG causes
      significant protein oxidation and damages components of the DNA repair proteome,
      including the Ku, OGG-1, MYH, and RPA proteins. Assays of DNA repair in intact
      cells or in cell extracts indicate that this protein damage compromises DNA break
      rejoining and base and nucleotide excision repair. As these experimental
      conditions simulate those in the skin of patients taking thiopurines, our
      findings suggest a mechanism whereby UVA in sunlight may contribute to skin
      carcinogenesis in immunosuppressed patients. 

PMID- 24284424
TI  - Chlorinated didemnins from the tunicate Trididemnum solidum.
AB  - Chemical investigation of the tunicate Trididemnum solidum resulted in the
      isolation of two new chlorinated compounds belonging to the didemnin class, along
      with two known compounds didemnin A and didemnin B. The structural determination
      of the compounds was based on extensive NMR and mass spectroscopic analysis. The
      isolated compounds 1-4 were tested for their anti-inflammatory activity using in
      vitro assays for inhibition of inducible nitric oxide synthase (iNOS) and nuclear
      factor-kappa B (NF-kappaB) activity. The anti-cell proliferative activity of the
      above compounds was also evaluated against four solid tumor cell lines. 

PMID- 24284425
TI  - Derivatives of salarin A, salarin C and tulearin A--Fascaplysinopsis sp.
      metabolites.
AB  - Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge
      derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of
      K562 leukemia cells. Interesting preliminary SAR (structure activity
      relationship) information was obtained from the products. The most sensitive
      functionalities were the 16,17-vinyl epoxide in both salarins, the triacylamino
      group in salarin A and the oxazole in salarin C (less sensitive).
      Regioselectivity of reactions was also found for tulearin A. 

PMID- 24284426
TI  - Simultaneous extraction and depolymerization of fucoidan from Sargassum muticum
      in aqueous media.
AB  - The biomass components of the invasive seaweed Sargassum muticum were
      fractionated to allow their separate valorization. S. muticum (Sm) and the solid
      residue remaining after alginate extraction of this seaweed (AESm) were processed
      with hot, compressed water (hydrothermal processing) to assess the effects of
      temperature on fucoidan solubilization. Fucose-containing oligosaccharides were
      identified as reaction products. Operating under optimal conditions (170  degrees
      C), up to 62 and 85 wt% of the dry mass of Sm and AESm were solubilized,
      respectively. The reaction media were subjected to precipitation, nanofiltration
      and freeze-drying. The dried products contained 50% and 85% of the fucoidan
      present in Sm and AESm, respectively; together with other components such as
      phenolics and inorganic components. The saccharidic fraction, accounting for up
      to 35% of the dried extracts, contained fucose as the main sugar, and also
      galactose, xylose, glucose and mannose. The concentrates were characterized for
      antioxidant activity using the TEAC assay. 

PMID- 24284427
TI  - Antiviral Sulfoquinovosyldiacylglycerols (SQDGs) from the Brazilian brown seaweed
      Sargassum vulgare.
AB  - Total lipids from the Brazilian brown seaweed Sargassum vulgare were extracted
      with chloroform/methanol 2:1 and 1:2 (v/v) at room temperature. After performing
      Folch partition of the crude lipid extract, the lipids recovered from the Folch
      lower layer were fractionated on a silica gel column eluted with chloroform,
      acetone and methanol. The fraction eluted with methanol, presented a strong
      orcinol-positive band characteristic of the presence of sulfatides when examined
      by TLC. This fraction was then purified by two successive silica gel column
      chromatography giving rise to fractions F4I86 and F4II90 that exhibited strong
      activity against herpes simplex virus type 1 and 2. The chemical structures
      present in both fractions were elucidated by ESI-MS and 1H/13C NMR analysis HSQC
      fingerprints based on their tandem-MS behavior as Sulfoquinovosyldiacylglycerols
      (SQDGs). The main SQDG present in both fractions and responsible for the anti
      herpes activity observed was identified as 1,2-di-O-palmitoyl-3-O-(6-sulfo-alpha
      D-quinovopyranosyl)-glycerol.

PMID- 24284428
TI  - Isolation and characterization of collagen and antioxidant collagen peptides from
      scales of croceine croaker (Pseudosciaena crocea).
AB  - Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was
      successfully isolated with the yield of 0.37% +/- 0.08% (dry weight basis), and
      characterized as type I collagen on the basis of amino acid analysis and
      electrophoretic pattern. The antioxidant hydrolysate of ASC-C (ACH) was prepared
      through a two-stage in vitro digestion (4-h trypsin followed by 4-h pepsin), and
      three antioxidant peptides (ACH-P1, ACH-P2, and ACH-P3) were further isolated
      from ACH using ultrafiltration, gel chromatography, and RP-HPLC, and their amino
      acid sequences were identified as GFRGTIGLVG (ACH-P1), GPAGPAG (ACH-P2), and
      GFPSG (ACH-P3). ACH-P1, ACH-P2, and ACH-P3 showed good scavenging activities on
      hydroxyl radical (IC50 0.293, 0.240, and 0.107 mg/mL, respectively), DPPH radical
      (IC50 1.271, 0.675, and 0.283 mg/mL, respectively), superoxide radical (IC50
      0.463, 0.099, and 0.151 mg/mL, respectively), and ABTS radical (IC50 0.421,
      0.309, and 0.210 mg/mL, respectively). ACH-P3 was also effectively against lipid
      peroxidation in the model system. The antioxidant activities of three collagen
      peptides were due to the presence of hydrophobic amino acid residues within the
      peptide sequences. The collagen peptides might be used as antioxidant for the
      therapy of diseases associated with oxidative stress, or reducing oxidative
      changes during storage.

PMID- 24284430
TI  - Efficient visible light driven photocatalytic hydrogen production from water
      using attapulgite clay sensitized by CdS nanoparticles.
AB  - Hydrogen production through water splitting using photocatalysts with solar
      energy can produce clean fuel from renewable resources. In this study, CdS
      nanoparticle sensitized attapulgite (ATP) nanocomposites were successfully
      prepared by a facile approach. Under visible-light irradiation, the as-prepared
      photocatalysts were used for photocatalytic water splitting for hydrogen
      evolution from aqueous solutions containing Na2SO3 and Na2S as sacrificial
      reagents even without the noble metals. Photocatalytic hydrogen production
      activity is ascribed to the presence of CdS nanocrystals that alter the energy
      levels of the conduction band and valence band in the coupled semiconductor
      system. Furthermore, the theoretical calculations show that the natural Fe doping
      (two ATP cells sharing one Fe atom) can promote the photocatalytic process.

PMID- 24284429
TI  - Pathways of lipid metabolism in marine algae, co-expression network, bottlenecks
      and candidate genes for enhanced production of EPA and DHA in species of
      Chromista.
AB  - The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human
      health has received more focus the last decades, and the global consumption of n
      3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested
      beyond a sustainable capacity, and it is therefore imperative to develop
      alternative n-3 LC-PUFA sources for both eicosapentaenoic acid (EPA, 20:5n-3) and
      docosahexaenoic acid (DHA, 22:6n-3). Genera of algae such as Nannochloropsis,
      Schizochytrium, Isochrysis and Phaedactylum within the kingdom Chromista have
      received attention due to their ability to produce n-3 LC-PUFAs. Knowledge of LC
      PUFA synthesis and its regulation in algae at the molecular level is fragmentary
      and represents a bottleneck for attempts to enhance the n-3 LC-PUFA levels for
      industrial production. In the present review, Phaeodactylum tricornutum has been
      used to exemplify the synthesis and compartmentalization of n-3 LC-PUFAs. Based
      on recent transcriptome data a co-expression network of 106 genes involved in
      lipid metabolism has been created. Together with recent molecular biological and
      metabolic studies, a model pathway for n-3 LC-PUFA synthesis in P. tricornutum
      has been proposed, and is compared to industrialized species of Chromista.
      Limitations of the n-3 LC-PUFA synthesis by enzymes such as thioesterases,
      elongases, acyl-CoA synthetases and acyltransferases are discussed and metabolic
      bottlenecks are hypothesized such as the supply of the acetyl-CoA and NADPH. A
      future industrialization will depend on optimization of chemical compositions and
      increased biomass production, which can be achieved by exploitation of the
      physiological potential, by selective breeding and by genetic engineering. 

PMID- 24284431
TI  - Polymer-free optode nanosensors for dynamic, reversible, and ratiometric sodium
      imaging in the physiological range.
AB  - This work introduces a polymer-free optode nanosensor for ratiometric sodium
      imaging. Transmembrane ion dynamics are often captured by electrophysiology and
      calcium imaging, but sodium dyes suffer from short excitation wavelengths and
      poor selectivity. Optodes, optical sensors composed of a polymer matrix with
      embedded sensing chemistry, have been translated into nanosensors that
      selectively image ion concentrations. Polymer-free nanosensors were fabricated by
      emulsification and were stable by diameter and sensitivity for at least one week.
      Ratiometric fluorescent measurements demonstrated that the nanosensors are
      selective for sodium over potassium by ~1.4 orders of magnitude, have a dynamic
      range centered at 20 mM, and are fully reversible. The ratiometric signal changes
      by 70% between 10 and 100 mM sodium, showing that they are sensitive to changes
      in sodium concentration. These nanosensors will provide a new tool for sensitive
      and quantitative ion imaging.

PMID- 24284432
TI  - Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in
      rheumatoid arthritis therapy.
AB  - Methotrexate (MTX) is a derivative of folic acid (folate) and commonly used as
      an anchor drug for the treatment of rheumatoid arthritis (RA). The
      pharmacokinetics (PK) and pharmacodynamics (PD) of MTX entirely depends on the
      function of specific transporters that belong to the two major superfamilies,
      solute carrier transporters and ATP-binding cassette transporters. Several
      transporters have been identified as being able to mediate the transport of MTX,
      and suggested to be involved in the disposition in the body and in the regulation
      of intracellular metabolism in target cells, together with several enzymes
      involved in folate metabolism. Thus, drug-drug interactions through the
      transporters and their genetic polymorphisms may alter the PK and PD of MTX,
      resulting in an interpatient variability of efficacy. This review summarizes the
      PK and PD of MTX, particularly in relation to RA therapy and focuses on the roles
      of transporters involved in PK and PD with the aim of facilitating an
      understanding of the molecular basis of the mechanism of MTX action to achieve
      its effective use in RA therapy. 

PMID- 24284433
TI  - Stigmatising attitudes towards people with mental disorders: results from a
      survey of Japanese high school students.
AB  - The aim of the current study was to assess the stigmatising attitudes of Japanese
      high school students towards people with depression, social phobia and
      psychosis/schizophrenia. In 2011, 311 students aged 15-18 years filled out an
      anonymous self-report questionnaire, which included a case vignette describing
      either depression, schizophrenia or social phobia and two questionnaires to
      assess stigmatising attitudes towards people with these disorders. Exploratory
      Structural Equation Modelling (ESEM) was used to determine the dimensionality and
      loading pattern of the stigma items in the two scales, to establish dimensions of
      stigma and to compare levels on these dimensions between genders. Stigmatising
      attitudes towards people with mental disorders in young Japanese people are
      substantial. ESEM revealed that the structure of stigmatising attitudes in young
      Japanese people is comparable in personal and perceived attitude stigma, with
      each forming distinct dimensions and each comprising 'weak not sick' and
      'dangerous/unpredictable' components. The social distance dimension of stigma was
      separate from other components. Stigmatising attitudes relating to
      dangerousness/unpredictability were the lowest for social phobia and highest for
      schizophrenia. Females had lower stigmatising attitudes than males. These
      findings echo those of Australian studies and extend them by demonstrating a
      similar structure of stigma in another cultural group, namely young Japanese
      people. 

PMID- 24284434
TI  - Binuclear ruthenium eta6-arene complexes with tetradentate N,S-ligands containing
      the ortho-aminothiophenol motif.
AB  - A series of cationic binuclear (eta(6)-cymene-Ru)2 complexes with N2S2-ligands
      were synthesized in 64% to 85% yield by reaction of [Ru(eta(6)-cymene)Cl2]2 with
      bis-S,S'-(ortho-aminothiophenol)-xylenes as BF4(-) and PF6(-) salts. The
      compounds were studied using NMR, HRMS, UV-vis and IR spectroscopy, EA and
      inductively coupled plasma (ICP) MS. It was determined that the hinged binuclear
      Ru complexes were anti and syn diastereomers obtained in 2 : 1 ratio for ortho-
      and meta-xylylene bridged ligands and in a 1 : 1 ratio for the para-xylylene
      bridged ligand. An anion effect was found for the presence of NaBF4 with the meta
      xylylene bridged system yielding the targeted binuclear Ru complex and a
      mononuclear Ru complex. This mononuclear S,S'-coordinated eta(6)-cymene Ru
      chloride structure lacked amine-metal coordination and was obtained in a 1 : 3
      ratio of anti : syn diastereomers which were insoluble in CH2Cl2 and soluble in
      DMSO and DMF. X-ray crystallographic analysis was obtained for the N2S2 ligand,
      1,2-bis{(2-aminophenyl)thiomethyl}benzene, showing a CS symmetry with amine
      groups facing outwards with a tilt of 28.95 degrees  from the ortho
      aminothiophenol pendant ring. The interatomic sulfur-sulfur distance (S-S') is
      4.6405 A within the crystal structure while accommodating a potential metal bite
      angle from 1.0 A to 5.9 A when allowing rotation of the methylene phenyl bond. 

PMID- 24284435
TI  - Slow-spinning low-sideband HR-MAS NMR spectroscopy: delicate analysis of
      biological samples.
AB  - High-Resolution Magic-Angle Spinning (HR-MAS) NMR spectroscopy has become an
      extremely versatile analytical tool to study heterogeneous systems endowed with
      liquid-like dynamics. Spinning frequencies of several kHz are however required to
      obtain NMR spectra, devoid of spinning sidebands, with a resolution approaching
      that of purely isotropic liquid samples. An important limitation of the method is
      the large centrifugal forces that can damage the structure of the sample. In this
      communication, we show that optimizing the sample preparation, particularly
      avoiding air bubbles, and the geometry of the sample chamber of the HR-MAS rotor
      leads to high-quality low-sideband NMR spectra even at very moderate spinning
      frequencies, thus allowing the use of well-established solution-state NMR
      procedures for the characterization of small and highly dynamic molecules in the
      most fragile samples, such as live cells and intact tissues. 

PMID- 24284437
TI  - Branched-chain amino acid requirements for enterally fed term neonates in the
      first month of life.
AB  - BACKGROUND: Knowledge of essential amino acid requirements in infants is
      important because excessive intake of protein can lead to increased long-term
      morbidity such as obesity. A deficient intake may lead to suboptimal growth and
      impaired neurodevelopment. The current recommended branched-chain amino acid
      requirements in infants aged 0-1 mo are based on the amino acid content of human
      milk. OBJECTIVE: We quantified the requirements for isoleucine, leucine, and
      valine for term neonates by using the indicator amino acid oxidation method with
      [1-(13)C]phenylalanine as the indicator. DESIGN: Fully enterally fed term infants
      received randomly graded amounts of isoleucine (5-216 mg . kg(-1) . d(-1)),
      leucine (5-370 mg . kg(-1) . d(-1)), or valine (5-236 mg . kg(-1) . d(-1)) as
      part of an elemental formula. Data are expressed as means +/- SDs. RESULTS:
      Eighty-three Asian, term neonates (mean +/- SD birth weight: 3.3 +/- 0.4 kg;
      gestational age: 39.4 +/- 1.3 wk) were studied at a postnatal age of 13 +/- 5 d.
      Mean requirements for isoleucine, leucine, and valine (measured in boys only)
      were 105 mg . kg(-1) . d(-1) (r(2) = 0.61, P < 0.001), 140 mg . kg(-1) . d(-1)
      (r(2) = 0.26, P < 0.01), and 110 mg . kg(-1) . d(-1) (r(2) = 0.35, P = 0.001),
      respectively. CONCLUSIONS: Current human milk-based recommendations for
      isoleucine and valine in term infants aged 0-1 mo are correct. However, the
      current recommendation for leucine (166 mg . kg(-1) . d(-1)) is higher than the
      mean requirement of 140 mg . kg(-1) . d(-1) that we determined in this study.
      This trial was registered at www.trialregister.nl as NTR1610.

PMID- 24284436
TI  - Associations between red meat intake and biomarkers of inflammation and glucose
      metabolism in women.
AB  - BACKGROUND: Greater red meat intake is associated with an increased type 2
      diabetes and cardiovascular disease risk. However, the relation of red meat
      intake to biomarkers of inflammation and glucose metabolism has not been
      investigated thoroughly. OBJECTIVE: We hypothesized that greater red meat intake
      would be associated with biomarkers of inflammation and glucose metabolism, which
      would be partly explained by body mass index (BMI). DESIGN: We analyzed cross
      sectional data from diabetes-free female participants in the Nurses' Health Study
      (n = 3690). Multiple linear regression was conducted to assess the associations
      of total, unprocessed, and processed red meat intakes (quartile categories) with
      plasma C-reactive protein (CRP), ferritin, adiponectin, fasting insulin, and
      hemoglobin A1c (Hb A1c). RESULTS: Greater total, unprocessed, and processed red
      meat intakes were associated with higher plasma CRP, ferritin, fasting insulin,
      and Hb A1c and lower adiponectin after adjustment for demographic information (P
      trend <= 0.03 for all). Adiponectin was not associated with any type of red meat
      intake when further adjusted for medical and lifestyle factors. After adjustment
      for BMI, most of these associations with inflammatory and glucose metabolic
      biomarkers were substantially attenuated and no longer significant. BMI accounted
      for a statistically significant proportion of associations with CRP, Hb A1c, and
      fasting insulin (P-contribution <= 0.02 for all) but not with ferritin.
      Substituting a serving of total red meat intake with alternative protein food in
      a combination of poultry, fish, legumes, and nuts was associated with
      significantly lower CRP (beta +/- SE: -0.106 +/- 0.043), ferritin (-0.212 +/-
      0.075), Hb A1c (-0.052 +/- 0.015), and fasting insulin (-0.119 +/- 0.036) (all P
      <= 0.02 for comparison of extreme quartiles for all). CONCLUSIONS: Greater red
      meat intake is associated with unfavorable plasma concentrations of inflammatory
      and glucose metabolic biomarkers in diabetes-free women. BMI accounts for a
      significant proportion of the associations with these biomarkers, except for
      ferritin. Substituting red meat with another protein food is associated with a
      healthier biomarker profile of inflammatory and glucose metabolism.

PMID- 24284438
TI  - Does behavioral intervention in pregnancy reduce postpartum weight retention?
      Twelve-month outcomes of the Fit for Delivery randomized trial.
AB  - BACKGROUND: Excessive weight gain during pregnancy is a risk factor for
      postpartum weight retention and future weight gain and obesity. Whether a
      behavioral intervention in pregnancy can reduce long-term weight retention is
      unknown. OBJECTIVE: This randomized trial tested whether a low-intensity
      behavioral intervention to prevent excessive gestational weight gain could
      increase the proportion of women who returned to prepregnancy weight by 12 mo
      postpartum. DESIGN: Women (n = 401, 13.5 wk of gestation, 50% normal weight, 50%
      overweight/obese) were randomly assigned into an intervention or control group;
      79% completed the 12-mo assessment. The telephone-based intervention targeted
      gestational weight gain, healthy eating, and exercise and was discontinued at
      delivery. RESULTS: In modified intent-to-treat analyses that excluded women with
      miscarriages (n = 6), gestational diabetes (n = 32), or subsequent pregnancies (n
      = 32), the intervention had no significant effect on the odds of achieving
      prepregnancy weight at 12 mo postpartum (n = 331; 35.4% compared with 28.1%; P =
      0.18). Completer analyses suggested that the intervention tended to increase the
      percentages of women who reached prepregnancy weight (n = 261; 45.3% compared
      with 35.3%; P = 0.09) and significantly reduced the magnitude of mean +/- SD
      postpartum weight retained (1.4 +/- 6.3 compared with 3.0 +/- 5.7 kg; P = 0.046)
      at 12 mo. Women in the intervention group reported higher dietary restraint
      through 6 mo postpartum (P = 0.023) and more frequent self-monitoring of body
      weight (P < 0.02 for all) throughout the study. CONCLUSIONS: A low-intensity
      behavioral intervention in pregnancy can reduce 12-mo postpartum weight retention
      and improve dietary restraint and self-weighing in study completers. Future
      research is needed to test the long-term effects of more intensive behavioral
      interventions in pregnancy. This trial was registered at clinicaltrials.gov as
      NCT01117961.

PMID- 24284439
TI  - Role of amino acid transporters in amino acid sensing.
AB  - Amino acid (AA) transporters may act as sensors, as well as carriers, of tissue
      nutrient supplies. This review considers recent advances in our understanding of
      the AA-sensing functions of AA transporters in both epithelial and nonepithelial
      cells. These transporters mediate AA exchanges between extracellular and
      intracellular fluid compartments, delivering substrates to intracellular AA
      sensors. AA transporters on endosomal (eg, lysosomal) membranes may themselves
      function as intracellular AA sensors. AA transporters at the cell surface,
      particularly those for large neutral AAs such as leucine, interact functionally
      with intracellular nutrient-signaling pathways that regulate metabolism: for
      example, the mammalian target of rapamycin complex 1 (mTORC1) pathway, which
      promotes cell growth, and the general control non-derepressible (GCN) pathway,
      which is activated by AA starvation. Under some circumstances, upregulation of AA
      transporter expression [notably a leucine transporter, solute carrier 7A5
      (SLC7A5)] is required to initiate AA-dependent activation of the mTORC1 pathway.
      Certain AA transporters may have dual receptor-transporter functions, operating
      as "transceptors" to sense extracellular (or intracellular) AA availability
      upstream of intracellular signaling pathways. New opportunities for nutritional
      therapy may include targeting of AA transporters (or mechanisms that upregulate
      their expression) to promote protein-anabolic signals for retention or recovery
      of lean tissue mass. 

PMID- 24284440
TI  - Breakfast consumption and physical activity in adolescents: daily associations
      and hourly patterns.
AB  - BACKGROUND: The association between breakfast consumption and physical activity
      (PA) is inconclusive. OBJECTIVE: We aimed to investigate daily associations and
      hourly patterns of PA and breakfast consumption in British adolescents. DESIGN:
      Daily PA [accelerometry-derived moderate and vigorous physical activity (MVPA)]
      and breakfast consumption (diet diary) were measured simultaneously over 4 d in
      860 adolescents (boys: 43.4%; mean +/- SD age: 14.5 +/- 0.5 y). Associations
      between MVPA and breakfast consumption were assessed by using a multilevel mixed
      effects logistic regression separately by sex and for weekends and weekdays.
      Hourly patterns of MVPA by breakfast consumption status were displayed
      graphically, and differences were tested by using ANOVA. Multilevel linear
      regression was used to investigate differences in log MVPA on days when 570
      inconsistent breakfast consumers ate or skipped breakfast. RESULTS: On weekends,
      boys and girls with higher MVPA were more likely to eat breakfast [OR (95% CI):
      boys, 1.78 (1.30, 2.45) (P < 0.001); girls, 2.30 (1.66, 3.08) (P < 0.001)] when
      adjusted for socioeconomic status, percentage of body fat, and total energy
      intake. Peak hourly MVPA differed for breakfast consumers compared with
      nonconsumers on weekends (P < 0.001). Inconsistent breakfast consumers did more
      MVPA on days when they ate breakfast [exponentiated beta coefficients (95% CIs):
      1.2 (1.0, 1.5) on weekdays and 1.4 (1.1, 1.8) on weekends for boys and 1.6 (1.3,
      2.1) on weekends for girls; all P < 0.03]. CONCLUSIONS: Eating breakfast was
      associated with higher MVPA on weekends. The time of peak MVPA differed between
      breakfast consumers and nonconsumers on weekends. Breakfast consumption at
      weekends is worth additional investigation to potentially inform PA promotion in
      adolescents.

PMID- 24284441
TI  - Control of the translational machinery by amino acids.
AB  - Amino acids are the precursors for the synthesis of proteins. In humans,
      approximately half of the 20 different amino acids are essential, ie, must be
      obtained from the diet. Cells must therefore take account of amino acid
      availability to achieve sustainable rates of protein synthesis. One of the major
      mechanisms involved in this is signaling through a complex of proteins termed
      mammalian target of rapamycin complex (mTORC) 1, which is activated by amino
      acids. In turn, mTORC1 regulates the production of ribosomes, the molecular
      machines that make proteins, and the activity of other cellular components
      required for protein synthesis. mTORC1 signaling promotes the transcription of
      the genes for ribosomal RNAs and many other components involved in ribosome
      production. It also positively regulates the translation of the messenger RNAs
      (mRNAs) for ribosomal proteins. Indeed, recent studies have shown that mammalian
      target of rapamycin signaling drives the translation of mRNAs for many anabolic
      enzymes and other proteins involved in diverse cellular functions. The
      translational machinery is also regulated by the absence of amino acids through
      the protein kinase GCN2 (general control nonrepressed 2), which phosphorylates
      and in end-effect inhibits the translation initiation factor eIF2 (eukaryotic
      initiation factor 2). This process shuts down general protein synthesis to
      conserve amino acids. 

PMID- 24284442
TI  - Leucine supplementation of a low-protein mixed macronutrient beverage enhances
      myofibrillar protein synthesis in young men: a double-blind, randomized trial.
AB  - BACKGROUND: Leucine is a key amino acid involved in the regulation of skeletal
      muscle protein synthesis. OBJECTIVE: We assessed the effect of the
      supplementation of a lower-protein mixed macronutrient beverage with varying
      doses of leucine or a mixture of branched chain amino acids (BCAAs) on
      myofibrillar protein synthesis (MPS) at rest and after exercise. DESIGN: In a
      parallel group design, 40 men (21 +/- 1 y) completed unilateral knee-extensor
      resistance exercise before the ingestion of 25 g whey protein (W25) (3.0 g
      leucine), 6.25 g whey protein (W6) (0.75g leucine), 6.25 g whey protein
      supplemented with leucine to 3.0 g total leucine (W6+Low-Leu), 6.25 g whey
      protein supplemented with leucine to 5.0 g total leucine (W6+High-Leu), or 6.25 g
      whey protein supplemented with leucine, isoleucine, and valine to 5.0 g total
      leucine. A primed continuous infusion of l-[ring-(13)C6] phenylalanine with
      serial muscle biopsies was used to measure MPS under baseline fasted and
      postprandial conditions in both a rested (response to feeding) and exercised
      (response to combined feeding and resistance exercise) leg. RESULTS: The area
      under the blood leucine curve was greatest for the W6+High-Leu group compared
      with the W6 and W6+Low-Leu groups (P < 0.001). In the postprandial period, rates
      of MPS were increased above baseline over 0-1.5 h in all treatments. Over 1.5-4.5
      h, MPS remained increased above baseline after all treatments but was greatest
      after W25 (~267%) and W6+High-Leu (~220%) treatments (P = 0.002). CONCLUSIONS: A
      low-protein (6.25 g) mixed macronutrient beverage can be as effective as a high
      protein dose (25 g) at stimulating increased MPS rates when supplemented with a
      high (5.0 g total leucine) amount of leucine. These results have important
      implications for formulations of protein beverages designed to enhance muscle
      anabolism. This trial was registered at clinicaltrials.gov as NCT 1530646.

PMID- 24284443
TI  - Maternal controlling feeding practices and girls' inhibitory control interact to
      predict changes in BMI and eating in the absence of hunger from 5 to 7 y.
AB  - BACKGROUND: Mothers use a range of feeding practices to limit children's intake
      of palatable snacks (eg, keeping snacks out of reach, not bringing snacks into
      the home), but less is known about the effects of these practices on children's
      eating and weight outcomes. OBJECTIVE: The objective was to identify distinct
      feeding practice profiles and evaluate the interactive effects of these profiles
      and girls' temperament (inhibitory control and approach) on girls' eating
      behaviors and weight outcomes at 5 and 7 y. DESIGN: Participants included 180
      mother-daughter dyads; measures were mothers' reports of controlling feeding
      practices and girls' height and weight, eating in the absence of hunger (EAH) at
      5 y, and inhibitory control (a measure of behavioral inhibition) and approach (a
      measure of appetitive motivation) at 7 y. RESULTS: Latent profile analysis of
      maternal feeding practices showed 4 feeding profiles based on maternal use of
      limit-setting practices and keeping snacks out of girls' physical reach, a
      restrictive practice: Unlimited Access to Snacks, Sets Limits+Does Not Restrict
      Snacks, Sets Limits+Restricts High Fat/Sugar Snacks, and Sets Limits+Restricts
      All Snacks. Girls whose mothers used Sets Limits+Restricts All Snacks had a
      higher approach and EAH at 5 y. Low inhibitory control girls whose mothers used
      Sets Limits+Restricts All Snacks or Unlimited Access to Snacks had greater
      increases in EAH and body mass index (BMI) from 5 to 7 y. CONCLUSIONS: Effects of
      maternal control on girls' EAH and BMI may differ by the type of practice used
      (eg, limit-setting or restrictive practices). Girls with low inhibitory control
      were more susceptible to the negative effects of low and high control.

PMID- 24284444
TI  - Calcium homeostasis and bone metabolic responses to high-protein diets during
      energy deficit in healthy young adults: a randomized controlled trial.
AB  - BACKGROUND: Although consuming dietary protein above current recommendations
      during energy deficit (ED) preserves lean body mass, concerns have been raised
      regarding the effects of high-protein diets on bone health. OBJECTIVE: The
      objective was to determine whether calcium homeostasis and bone turnover are
      affected by high-protein diets during weight maintenance (WM) and ED. DESIGN: In
      a randomized, parallel-design, controlled trial of 32 men and 7 women, volunteers
      were assigned diets providing protein at 0.8 [Recommended Dietary Allowance
      (RDA)], 1.6 (2 * RDA), or 2.4 (3 * RDA) g . kg(-1) . d(-1) for 31 d. Ten days of
      WM preceded 21 d of ED, during which total daily ED was 40%, achieved by reduced
      dietary energy intake (~30%) and increased physical activity (~10%). The
      macronutrient composition (protein g . kg(-1) . d(-1) and % fat) was held
      constant from WM to ED. Calcium absorption (ratio of (44)Ca to (42)Ca) and
      circulating indexes of bone turnover were determined at day 8 (WM) and day 29
      (ED). RESULTS: Regardless of energy state, mean (+/-SEM) urinary pH was lower (P
      < 0.05) at 2 * RDA (6.28 +/- 0.05) and 3 * RDA (6.23 +/- 0.06) than at the RDA
      (6.54 +/- 0.06). However, protein had no effect on either urinary calcium
      excretion (P > 0.05) or the amount of calcium retained (P > 0.05). ED decreased
      serum insulin-like growth factor I concentrations and increased serum tartrate
      resistant acid phosphatase and 25-hydroxyvitamin D concentrations (P < 0.01).
      Remaining markers of bone turnover and whole-body bone mineral density and
      content were not affected by either the protein level or ED (P > 0.05).
      CONCLUSION: These data demonstrate that short-term consumption of high-protein
      diets does not disrupt calcium homeostasis and is not detrimental to skeletal
      integrity. This trial was registered at www.clinicaltrials.gov as NCT01292395.

PMID- 24284446
TI  - Vitamin D supplementation and risk of infectious disease: no easy answers.

PMID- 24284445
TI  - Integration of signals generated by nutrients, hormones, and exercise in skeletal
      muscle.
AB  - This review focuses on anabolic signaling pathways through which insulin, amino
      acids, and resistance exercise act to regulate the protein kinase complex
      referred to as mechanistic target of rapamycin complex (mTORC) 1. Initially,
      individual pathways through which the 3 anabolic signals act to modulate mTORC1
      signaling will be discussed, followed by a summation of evidence showing an
      additive effect of the regulators. The emphasis will be on mTORC1 signaling in
      skeletal muscle and its contribution to modulation of rates of protein synthesis.
      In addition, results from studies using cells in culture will be used to provide
      a more complete picture of the molecular details of the individual pathways. 

PMID- 24284447
TI  - Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are
      associated with susceptibility to Crohn disease.
AB  - BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) are 2 common
      inflammatory bowel diseases (IBDs) associated with intestinal inflammation and
      tissue damage. Oxidative stress is suggested to play a major role in the
      initiation and progression of IBD. Vitamin C (ascorbate, ascorbic acid)
      supplementation has reduced oxidative stress in persons with IBD. The role of
      ascorbate transporters in IBD remains to be determined. SLC23A1 is a major
      ascorbate transporter in the intestinal tract, and some of its genetic variants
      have been associated with severely decreased ascorbate transport and lower
      systemic concentrations. OBJECTIVE: This study aimed to determine whether common
      genetic variants in the vitamin C transporter SLC23A1 are associated with the
      risk of IBD. DESIGN: Genomic DNA samples from patients with CD (n = 162) and UC
      (n = 149) from the Manitoba IBD Cohort Study and ethnically matched controls (n =
      142) were genotyped for 3 SLC23A1 polymorphisms (rs6596473, rs33972313, and
      rs10063949) by using TaqMan assays. RESULTS: Variation at rs10063949 (G allele
      for heterozygote and homozygote) was associated with increased susceptibility to
      CD (OR: 2.54; 95% CI: 1.38, 4.66; OR: 4.72; 95% CI: 2.53, 8.81; P < 0.0001;
      respectively). A strong linkage disequilibrium (LD) was observed across the
      SLC23A1 region (variation rs6596473 with rs10063949) for CD and UC (D' = 0.94 and
      0.96, respectively). The risk alleles confirmed a haplotype (CGG) that is carried
      more in CD patients (65.3%, P < 0.0001) than in controls (43.5%). CONCLUSIONS: A
      genetic variant (rs10063949-G) in the SLC23A1 ascorbate transporter locus was
      identified and is associated with an increased risk of CD in a white Canadian IBD
      cohort. The presented evidence that SLC23A1 variations can modulate the risk of
      CD has implications for understanding ascorbate transport in CD patients and
      provides a novel opportunity toward individualized nutritional therapy for
      patients carrying the disease-associated genotype.

PMID- 24284448
TI  - [Massage therapy in preterm infants].

PMID- 24284450
TI  - Editorial.

PMID- 24284451
TI  - Recognition of nonverbal communication of emotion after traumatic brain injury.
AB  - BACKGROUND: Individuals who have had a traumatic brain injury (TBI) often have
      difficulty processing nonverbal communication (Ekman, 1976) The published
      research in this area has focused on a TBI patient's ability to recognize facial
      expression, vocal intonation, and postural expression (Croker, 2005; Hopkins,
      Dywan & Segalowitz, 2002). OBJECTIVE: This study compared the non-verbal
      processing skills of brain-injured patients versus non-injured controls in all
      three domains. METHODS: The stimuli were photographs of facial and postural
      expressions and audio recordings of intonational expressions. RESULTS: The
      results indicated that persons with TBI have particular difficulty recognizing
      non-verbal communication resulting from vocal intonations. CONCLUSIONS: The TBI
      patients had difficulty processing tonality, therefore, it is reasonable to
      suggest that clinicians, friends, and family members should emphasize the
      explicit verbal content of spoken language when speaking to a person with TBI.

PMID- 24284452
TI  - Pediatric cognitive rehabilitation: effective treatments in a school-based
      environment.
AB  - BACKGROUND: Many studies have investigated the impact of pediatric Cognitive
      Rehabilitation Therapy (CRT) upon intellectual functioning after traumatic brain
      injury; however, relatively few have identified efficacious treatment in a school
      setting. OBJECTIVE: The purpose is to present a variety of CRT strategies that
      would be useful to a teacher or therapist working with students who are learning
      disabled or who have who have had a traumatic brain injury (TBI). METHODS: This
      article investigates the particular challenges in learning which result from
      impaired cognition, and suggests techniques for improving memory and executive
      functioning. RESULTS: Students who are learning disabled or who have TBI face
      social and emotional issues that impact their learning. Special therapeutic
      interventions are necessary to assist with orienting to their setting,
      integrating with peers, and coping with distressing emotions. CONCLUSIONS:
      Students with TBI can adapt and flourish in a school based setting provided that
      therapies and learned strategies are targeted to their specific needs.

PMID- 24284453
TI  - Effect of rhythmic auditory stimulation on gait and balance in hemiplegic stroke
      patients.
AB  - BACKGROUND: Rhythmic auditory stimulation (RAS) improves gait velocity, cadence,
      and stride length in hemiplegic stroke patients, yet little is known about the
      effectiveness of RAS on standing balance. OBJECTIVES: To examine and compare the
      effectiveness on standing balance and gait parameter of two different types of
      gait trainings, gait training with RAS versus gait training without RAS, was
      compared in two groups of hemiplegic stroke patients over a three-week period
      (RAS group, n = 8; control group = 8). METHODS: Sixteen hemiplegic stroke
      patients were included in the study. Standing balance was measured by using
      Biosway(r). Stride length, gait velocity, and cadence were calculated from the
      number of steps and required time for a 10 m-walk. RESULTS: Pre- to post-test
      measures showed a significant improvement in RAS group for overall stability
      index (p = 0.043), mediolateral index (p = 0.006), anteroposterior index (p =
      0.016), gait velocity (p = 0.012), stride length (p = 0.03) and cadence (p =
      0.012) over the control group. CONCLUSIONS: The results of this study showed that
      RAS was an effective therapeutic method to improve gait velocity, stride length,
      cadence, and standing balance in hemiplegic stroke patients.

PMID- 24284454
TI  - Expressive writing in people with traumatic brain injury and learning disability.
AB  - BACKGROUND: There is a dearth of systematic studies of expressive writing
      disorder (EWD) in persons with Traumatic Brain Injury (TBI). It is unclear if TBI
      survivors' written expression differs significantly from that experienced by
      persons with learning disabilities. It is also unclear which cognitive or
      neuropsychological variables predict problems with expressive writing (EW) or the
      EWD. OBJECTIVE: This study investigated the EW skill, and the EWD in adults with
      mild traumatic brain injuries (TBI) relative to those with learning disabilities
      (LD). It also determined which of several cognitive variables predicted EW and
      EWD. METHODS: Principle Component Analysis (PCA) of writing samples from 28 LD
      participants and 28 TBI survivors revealed four components of expressive writing
      skills: Reading Ease, Sentence Fluency, Grammar and Spelling, and Paragraph
      Fluency. RESULTS: There were no significant differences between the LD and TBI
      groups on any of the expressive writing components. Several neuropsychological
      variables predicted skills of written expression. The best predictors included
      measures of spatial perception, verbal IQ, working memory, and visual memory.
      CONCLUSIONS: TBI survivors and persons with LD do not differ markedly in terms of
      expressive writing skill. Measures of spatial perception, visual memory, verbal
      intelligence, and working memory predict writing skill in both groups. Several
      therapeutic interventions are suggested that are specifically designed to improve
      deficits in expressive writing skills in individuals with TBI and LD.

PMID- 24284455
TI  - Cognitive status does not predict motor gain from post stroke constraint-induced
      movement therapy.
AB  - BACKGROUND: Constraint-Induced Movement Therapy (CIMT) is an evidence-based
      rehabilitation intervention for stroke. Several factors influence the motor gain
      from CIMT, including age and level of impairment. However, it is currently
      unknown to what extent cognitive status affects motor gain during CIMT.
      OBJECTIVE: The aim of this study was to investigate whether cognitive and
      emotional status affects motor improvement during two weeks of CIMT and retention
      of the gain at three months follow-up. METHODS: Twenty stroke patients (3-12
      months post stroke) completed two weeks of CIMT. Motor performance was measured
      using the Wolf Motor Function Test (WMFT). Cognitive and emotional status was
      measured with a comprehensive neuropsychological test battery and a questionnaire
      on emotional status. All measures were performed at baseline, after two weeks of
      training, and at three months follow-up. RESULTS: We found no significant
      correlation between cognitive or emotional measures at baseline and improvement
      in motor performance post training. Also, cognitive and emotional status did not
      correlate with motor retention at three months follow-up. CONCLUSIONS: We found
      no evidence to support that cognitive performance in stroke patients can predict
      motor gain from CIMT.

PMID- 24284456
TI  - Deficit awareness and cognitive performance in individuals with acquired brain
      injury.
AB  - BACKGROUND: Anosognosia is commonly reported after acquired brain injury (ABI) or
      stroke and often hinders an ABI survivor's ability to perceive the social
      consequences of their behavior and to modify it. OBJECTIVE: This study concerned
      the question of whether awareness discrepancy scores could predict cognitive
      performance with a focus on the acquired brain injured (ABI) population. It was
      hypothesized that lack of awareness would predict performance on cognitive tasks.
      METHOD: Archival data was assessed for a total of 21 patients; 10 learning
      disabled (LD) and 11 with a brain injury with each person having one "observer".
      Data consisted of patient and observer ratings on the Acquired Deficit Awareness
      Management System (ADAMS) profile, a 36-item survey that measured both patient
      self-report and observer assessment of awareness. These data yielded two
      discrepancy scores: deficit with awareness (DWA) and deficit without awareness
      (DWoA). The discrepancy scores were used to predict IQ scores from the Wechsler
      Adult Intelligence Scale, academic performance on the Woodcock-Johnson
      Psychoeducational Battery, memory functioning on the Wechsler Memory Scale, and a
      measure of fine motor skill. RESULTS: The DWoA measure correlated significantly
      with several cognitive variables and with finger tapping speed on the non
      dominant hand. These correlations were not apparent in the LD group. CONCLUSIONS:
      Measures of lack of awareness predicted cognitive performance in the ABI
      population. Therapeutic interventions are discussed that address lack of
      awareness after ABI.

PMID- 24284457
TI  - Executive function and coping in stroke survivors.
AB  - BACKGROUND: Stroke is a leading cause of disability and sequelae may include
      physical, emotional, and cognitive impairments. The methods employed to cope with
      distress, both emotional and cognitive, have not been evaluated in individuals
      post-stroke. However, research in traumatic brain injury (TBI) suggests that
      executive function is positively correlated with adaptive coping and negatively
      correlated with maladaptive coping strategies (Krpan et al., 2007). Examination
      of these constructs post-stroke may assist with enriching our understanding of
      cognitive and emotional symptomatology and optimize rehabilitation strategies.
      OBJECTIVE: The present study aimed to assess the association between executive
      function and coping strategies in a sample of chronic stroke survivors. The
      researchers hypothesized that executive function would be positively correlated
      with adaptive coping strategies and negatively correlated with maladaptive coping
      strategies. METHODS: Fifteen stroke survivors were administered a battery of
      cognitive tests assessing executive function and also completed the Ways of
      Coping Questionnaire (WAYS), a self-report coping measure. RESULTS: Analyses
      indicated that executive function deficits were related to increased avoidant
      coping. Contrary to expectations, executive function was not significantly
      related to active coping. In addition, post hoc analyses revealed that executive
      function was a significant predictor of avoidant coping after controlling for
      demographics. CONCLUSIONS: Our data, in accordance with prior work in TBI,
      suggests that executive function and aspects of coping are associated.
      Rehabilitation strategies that improve executive function may also lead to
      utilization of adaptive coping strategies. Research has shown that aerobic
      exercise increases activation in the frontal lobe and improves executive function
      (Colcombe & Kramer, 2003; Colcombe et al., 2004). Future studies should examine
      whether aerobic exercise positively affects executive function and coping in
      stroke survivors.

PMID- 24284458
TI  - Clinical reasoning in cognitive rehabilitation therapy.
AB  - BACKGROUND: Many who provide cognitive rehabilitation therapy (CRT) are unaware
      of the theoretical rationale that underlies their decisions concerning
      therapeutic intervention. Can the survivor form goals for treatment? When should
      treatment end? When should the therapist retrain skills, provide remedial
      cognitive treatments, or simply adapt surroundings because a survivor is too
      handicapped to be treated at all? OBJECTIVE: This paper combines theory with the
      author's experience to provide therapists with a structure for clinical reasoning
      in their daily practice. METHOD: The discussion begins with a description of
      different models of recovery after brain injury. It goes on to discuss
      similarities, commonalities, and general principles that can be derived from all
      of them. It ends with suggestions for treatment that serve as useful guidelines
      for therapists in their practices. CONCLUSION: Combining the clinician's clinical
      intuition with knowledge of the theory of CRT can greatly improve the quality of
      treatment the therapist provides.

PMID- 24284459
TI  - Family needs and TBI caregiver mental health in Guadalajara, Mexico.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death in Mexico,
      and Mexican TBI caregivers have been shown to experience significant mental
      health problems and high levels of family needs. OBJECTIVE: This study
      investigated the associations between family needs and Mexican TBI caregiver
      mental health. METHODS: Ninety TBI caregivers from Guadalajara, Mexico completed
      measures assessing their own mental health (depression, anxiety, burden,
      satisfaction with life, and self-esteem) and family needs (physical health,
      informational, financial, social support, and household). RESULTS: Family health
      needs were uniquely associated with all indices of caregiver mental health, and
      household needs were uniquely associated with caregiver depression, burden, and
      anxiety. Additionally, social support needs were related to caregiver
      satisfaction with life, informational needs to burden, and financial needs to
      self-esteem. CONCLUSIONS: Interventions for TBI caregivers in Mexico-and likely
      in other global regions with high levels of familism-should include an emphasis
      on overall family health, the delineation of family roles regarding household
      responsibilities, the improvement of social support networks and the social
      presence of family members, and the provision of complete and relevant
      information regarding TBI. When these needs are more comprehensively met,
      caregiver mental health will likely improve.

PMID- 24284460
TI  - Bridging the gap between clinical neuroscience and cognitive rehabilitation: the
      role of cognitive training, models of neuroplasticity and advanced neuroimaging
      in future brain injury rehabilitation.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has brought about advances in the
      fields of brain plasticity and lifespan brain change, that might be of special
      interest for cognitive rehabilitation research and, eventually, in clinical
      practice. Parallel, intensive cognitive training studies show promising results
      for the prospect of retraining some of the impaired functioning following
      acquired brain injury. OBJECTIVES: However, cognitive training research is
      largely performed without concurrent assessments of brain structural change and
      reorganization, which could have addressed possible mechanisms of training
      related neuroplasticity. METHODS: Criticism of cognitive training studies is
      often focused on lack of ecologically valid, daily-living assessments of
      treatment effect, and on whether the applied cognitive measures overlap too much
      with the training exercises. Yet, the present paper takes another point of view,
      where the relevance of recent MRI research of brain plasticity to the field of
      cognitive rehabilitation is examined. RESULTS: Arguably, treatment ought to be
      measured at the same level of the International Classification of Functioning,
      Disability and Health model, as it is targeting. In the case of cognitive
      training that will be the "body structure" and "body function" levels.
      CONCLUSIONS: MRI has shown promise to detect macro- and microstructural activity
      related changes in the brain following intensive training.

PMID- 24284461
TI  - Return to driving in the first 6 months of community integration after acquired
      brain injury.
AB  - BACKGROUND: Return to driving is a goal and milestone in the recovery process
      following acquired brain injury (ABI). Knowledge of whether and when a person is
      likely to return to driving is important to people with ABI, family members and
      clinicians. OBJECTIVE: To determine the rates, timing, correlates, and predictors
      of return to driving in the first 6 months after discharge from hospital
      following ABI. METHODS: Survey of 212 participants with ABI and 121 family
      members at discharge and 3 and 6 months later. Participants with ABI were grouped
      according to driving status (not driving, returned within 3 months, returned
      within 6 months). Groups were compared on demographics, injury severity, quality
      of life, functioning, psychosocial integration, depression, and carer well-being.
      RESULTS: By 6 months post-discharge 62.3% had resumed driving. Between group
      differences existed on measures of injury severity, and psychosocial integration
      at 6 months, and carer depression and strain at discharge and 6 months. Whether
      and when someone returned to driving could be predicted by length of hospital
      stay, and level of community integration, and pain at discharge. CONCLUSIONS:
      Educating clients about their likelihood and timing of return to driving, and
      supporting non-drivers and their carers may improve psychosocial outcomes.

PMID- 24284462
TI  - Electrophysiological evaluation of the Modified Tardieu Scale (MTS) in assessing
      poststroke wrist flexor spasticity.
AB  - BACKGROUND: Spasticity is a common impairment following upper motor neuron
      lesions such as stroke. The appropriate measurement of muscle spasticity using
      validated tools to evaluate the outcome of therapies is important in clinical and
      research settings. OBJECTIVE: To determine the concurrent criterion-related
      validity of the Modified Tardieu Scale (MTS) in assessing poststroke wrist flexor
      muscle spasticity based on its correlation with H-reflex tests. METHODS: A total
      of 20 adult patients poststroke underwent clinical and electrophysiological
      assessment of wrist flexor muscle spasticity on the affected side. The primary
      outcome measures were: R2-R1 of the MTS; and the H-reflex indices of Hmax/Mmax
      ratio and Hslp/Mslp ratio. The Hslp and the latency of H-reflex were also
      measured. RESULTS: Correlations tests did not reveal significant associations
      between the clinical and H-reflex tests. CONCLUSIONS: This study suggests that
      the MTS may not be a valid tool to evaluate muscle spasticity in this sample of
      patients after stroke.

PMID- 24284463
TI  - Aerobic exercises enhance cognitive functions and brain derived neurotrophic
      factor in ischemic stroke patients.
AB  - BACKGROUND: Stroke is a leading cause of functional impairments. High percentage
      of these patients will experience some degree of cognitive affection, ranging
      from mild cognitive impairment to dementia. OBJECTIVE: Demonstrate the role of
      aerobic exercises enhancing cognitive functions and its effect on Brain Derived
      Neurotrophic factor (BDNF) in post-ischemic stroke patients in the territory of
      anterior circulation. SUBJECTS AND METHODS: We included thirty Egyptian ischemic
      stroke patients in the territory of anterior circulation. They were divided into
      2 groups; group 1 (G1) were subjected to physiotherapy program without aerobic
      exercises and group 2 (G2) were subjected to the same previous program followed
      by aerobic exercises. Both groups were subjected to pre- and post-treatment
      Addenbrookes's Cognitive Examination- Revised (ACER) and serum level of BDNF.
      RESULTS: Our results showed a significant improvement in ACER score in G2
      compared to G1 post-treatment (p = 0.017). BDNF serum level significantly
      increased in G2 post-treatment compared to pre-treatment (p = 0.001) and compared
      to G1 group (p = 0.0458). ACER improvement was positively correlated to increase
      in serum level of BDNF (r = 0.53, p = 0.044). CONCLUSION: Aerobic exercises
      improve cognitive functions of ischemic stroke patients. This improvement is
      related to the increase in serum level of BDNF.

PMID- 24284464
TI  - Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.
AB  - BACKGROUND: The debilitating fatigue that patients with multiple sclerosis (MS)
      commonly experience during day-to-day living activities responds poorly to
      current therapeutic options. Direct currents (DC) delivered through the scalp
      (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor
      cortical excitability that persist for almost an hour after current offset and
      depend on current polarity. tDCS successfully modulates cortical excitability in
      various clinical disorders but no information is available for MS related
      fatigue. OBJECTIVE: In this study we aimed to assess fatigue symptom after five
      consecutive sessions of anodal tDCS applied over the motor cortex in patients
      with MS. METHODS: We enrolled 25 patients with MS all of whom experienced
      fatigue. We delivered anodal and sham tDCS in random order in two separate
      experimental sessions at least 1 month apart. The stimulating current was
      delivered for 15 minutes once a day for 5 consecutive days. In each session the
      Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were
      administered before the treatment (baseline), immediately after treatment on day
      five (T1), one week (T2) and three weeks (T3) after the last tDCS session.
      RESULTS: All patients tolerated tDCS well without adverse events. The fatigue
      score significantly decreased after anodal tDCS in 65% of the patients
      (responders). After patients received tDCS for 5 days their FIS scores improved
      by about 30% and the tDCS-induced benefits persisted at T2 and T3. CONCLUSION:
      Our preliminary findings suggest that anodal tDCS applied over the motor cortex,
      could improve fatigue in most patients with MS.

PMID- 24284465
TI  - Meaningful improvement in walking performance after Botulinum neurotoxin A (BoNT
      A) in chronic spastic patients.
AB  - BACKGROUND: Botulinum neurotoxin A (BoNT-A) may reduce lower limb spasticity but
      its role in improving walking ability remains to be established. OBJECTIVE: To
      investigate the efficacy of simultaneous BoNT-A injections into several targeted
      spastic muscles of different joints on gait speed and on functional gains in gait
      performance in chronic stroke and MS patients. METHODS: Twenty patients affected
      by stroke or multiple sclerosis were tested before, one and three months after
      BoNT-A administration. Gait was evaluated by the 10 Meter Walk Test; patients
      were stratified into functional ambulation classes accordingly. Spasticity was
      assessed using the modified Ashworth Scale. RESULTS: At final assessment,
      spasticity was reduced in hip adductors and ankle plantar-flexors, gait speed
      improved and, 1/3rd of patients transitioned to a higher ambulation class. The
      pre-post difference in Level of Spasticity of the hips was a predictor for an
      increase in gait speed. CONCLUSIONS: A meaningful improvement in walking
      performance can be obtained in chronic spastic patients after BoNT-A injection
      into several muscles, specifically the hip adductors.

PMID- 24284466
TI  - A description of cognitive rehabilitation at Sunnaas Rehabilitation Hospital-
      balancing comprehensive holistic rehabilitation and retraining of specific
      functional domains.
AB  - BACKGROUND: Measures of cognitive rehabilitation should include comprehensive
      holistic rehabilitation as well as interventions targeting specific cognitive
      functions; it is however not clear how this knowledge should be put into
      practice. OBJECTIVE: To describe services provided at the cognitive
      rehabilitation unit at Sunnaas Rehabilitation Hospital (SRH), a regional
      rehabilitation centre in Norway. METHODS: Cognitive rehabilitation programs
      offered at SRH are described. For all patients served in 2011 and 2012,
      epidemiological and hospitalization related data were retrieved. Results from a
      patient satisfaction survey are presented. RESULTS: The services include
      individual holistic cognitive rehabilitation as well as group programs. 307
      individual patients were served in 355 hospitalizations; 68.1% were male; age
      ranged from 18 to 78 years. The largest patient groups were stroke (46.6%) and
      traumatic brain injury (33.0%). Mean length of stay was 36.9 days. Median time
      post injury was 0.8 years (range 16 days - 14 years). More than 90% of the
      patients were satisfied with the services they received to a large or very large
      extent. CONCLUSIONS: Providing cognitive rehabilitation that encompasses both a
      holistic approach and targets specific cognitive functions is challenging. More
      research is warranted to illuminate further how cognitive rehabilitation services
      should be designed and conducted in practice.

PMID- 24284467
TI  - Phosphodiesterase inhibition facilitates cognitive restoration in rodent models
      of age-related memory decline.
AB  - BACKGROUND: Previous studies have shown that cyclic nucleotide phosphodiesterase
      type 5 (PDE5) inhibition with the drugs sildenafil and vardenafil can enhance
      spatial performance and object recognition in rodent models of learning and
      memory. OBJECTIVE: We review recent studies on PDE5 inhibition and report novel
      data that specifically tests the systemic effects of both pharmacological agents
      in aged rats using two different spatial learning/memory paradigms. METHODS: The
      14-unit T-maze was used as a test of egocentric spatial processing that requires
      rats to learn a series of left/right turns to avoid mild footshock. The Morris
      water maze is a test of allocentric spatial learning that requires the
      acquisition of place information to localize a hidden platform relative to distal
      room cues. RESULTS: In both cases, acquisition (i.e., learning performance) was
      not improved, however after a one week drug washout period, aged animals
      demonstrated improved spatial memory retention compared to aged controls, ruling
      out simple performance effects. CONCLUSIONS: These findings are discussed in
      relation to recent reports on the use of PDE inhibitors to treat Alzheimer's
      disease (AD) dementia and age-related memory impairments. While some report
      promising pre-clinical results, others note that PDE5 may not be an appropriate
      target in AD due to a lack of localization within critical brain structures where
      therapeutic activity is needed. Despite these limitations, PDE5 inhibition may
      produce beneficial effects via several mechanisms that target predisposing risk
      factors leading to increased incidence of memory impairment in aged individuals
      and influence memory consolidation mechanisms that preserve long-term retention
      of cognitive information.

PMID- 24284468
TI  - Effects of perceptive rehabilitation on balance control in patients with
      Parkinson's disease.
AB  - BACKGROUND: Subjects affected by Parkinson's disease have substantially impaired
      static and dynamic balance, leading to diminished functional ability.
      Conventional and innovative exercises have been suggested, but most of them were
      focused on motor features of posture and gait, deserving poor attention to
      perceptive aspects of balance. OBJECTIVE: To evaluate the efficacy of the
      perceptive rehabilitation, based on perceptual surfaces, for postural balance
      (primary aim) and pain, depression and activity daily living. METHODS: In this
      pilot study, we have treated 9 patients with Parkinson's disease undergone
      rehabilitation aiming to restoring their correct body midline perception,
      according a schema treatment - no treatment - treatment. RESULTS: During the
      rehabilitative intervention, both Tinetti balance score (p = 0.007 in both
      phases) and Tinetti gait score (p = 0.011 and p = 0.016, respectively), such as
      pain relief assessed by Visual Analogue Scale (p = 0.011, p = 0.010) were
      improved. Conversely in the phase of no-intervention, lasting the same amount of
      time, it was showed a significant reduction of Tinetti Balance score (p = 0.010)
      and no significant changes in terms of Tinetti Gait score and Visual Analogue
      Scale. CONCLUSIONS: These preliminary results highlighted the importance of
      introducing perceptive training into the exercises proposed to patients with
      Parkinson's disease for reducing both their static and dynamic balance
      impairments.

PMID- 24284469
TI  - Back home after an acquired brain injury: building a "low-cost" team to provide
      theory-driven cognitive rehabilitation after routine interventions.
AB  - BACKGROUND: Individuals with Acquired Brain Injury (ABI) could benefit from
      further cognitive rehabilitation, after they have returned home. However, a lack
      of specialist services to provide such rehabilitation often prevents this. This
      leads to reduced reintegration of patients, increased social disadvantages and
      ultimately, higher economic costs. METHOD: 10 months post-stroke, a 69 year-old
      woman was discharged from an inpatient rehabilitation program and returned home
      with severe cognitive impairments. We describe a pilot project which provided an
      individualised, low cost rehabilitation program, supervised and trained by a
      neuropsychologist. Progress was monitored every 3 months in order to decide on
      continuation of the program, based on the achieved results and predicted costs.
      RESULTS: Post intervention, despite severe initial impairment, cognitive and most
      notably daily functioning had improved. Although the financial investment was
      moderately high for the family, the intervention was still considered cost
      effective when compared with the required costs of care in a local non-specialist
      care home. Moreover, the pilot experience was used to build a "local expert team"
      available for other individuals requiring rehabilitation. CONCLUSIONS: These
      results encourage the development of similar local "low cost" teams in the
      community, to provide scientifically-grounded cognitive rehabilitation for ABI
      patients returning home.

PMID- 24284470
TI  - Oculomotor neurorehabilitation for reading in mild traumatic brain injury (mTBI):
      an integrative approach.
AB  - BACKGROUND: Considering the extensive neural network of the oculomotor
      subsystems, traumatic brain injury (TBI) could affect oculomotor control and
      related reading dysfunction. OBJECTIVE: To evaluate comprehensively the effect of
      oculomotor-based vision rehabilitation (OBVR) in individuals with mTBI. METHODS:
      Twelve subjects with mTBI participated in a cross-over, interventional study
      involving oculomotor training (OMT) and sham training (ST). Each training was
      performed for 6 weeks, 2 sessions a week. During each training session, all three
      oculomotor subsystems (vergence/accommodation/version) were trained in a
      randomized order across sessions. All laboratory and clinical parameters were
      determined before and after OMT and ST. In addition, nearvision-related symptoms
      using the Convergence Insufficiency Symptom Survey (CISS) scale and subjective
      visual attention using the Visual Search and Attention Test (VSAT) were assessed.
      RESULTS: Following the OMT, over 80% of the abnormal parameters significantly
      improved. Reading rate, along with the amplitudes of vergence and accommodation,
      improved markedly. Saccadic eye movements demonstrated enhanced rhythmicity and
      accuracy. The improved reading-related oculomotor behavior was reflected in
      reduced symptoms and increased visual attention. None of the parameters changed
      with ST. CONCLUSIONS: OBVR had a strong positive effect on oculomotor control,
      reading rate, and overall reading ability. This oculomotor learning effect
      suggests considerable residual neuroplasticity following mTBI.

PMID- 24284471
TI  - [Update and focus on arterial vascular surgeries from the II Guidelines for
      Perioperative Evaluation of the Brazilian Society of Cardiology].

PMID- 24284472
TI  - Dynamic optical projection of acquired luminescence for aiding oncologic surgery.
AB  - Optical imaging enables real-time visualization of intrinsic and exogenous
      contrast within biological tissues. Applications in human medicine have
      demonstrated the power of fluorescence imaging to enhance visualization in
      dermatology, endoscopic procedures, and open surgery. Although few optical
      contrast agents are available for human medicine at this time, fluorescence
      imaging is proving to be a powerful tool in guiding medical procedures. Recently,
      intraoperative detection of fluorescent molecular probes that target cell-surface
      receptors has been reported for improvement in oncologic surgery in humans. We
      have developed a novel system, optical projection of acquired luminescence
      (OPAL), to further enhance real-time guidance of open oncologic surgery. In this
      method, collected fluorescence intensity maps are projected onto the imaged
      surface rather than via wall-mounted display monitor. To demonstrate proof-of
      principle for OPAL applications in oncologic surgery, lymphatic transport of
      indocyanine green was visualized in live mice for intraoperative identification
      of sentinel lymph nodes. Subsequently, peritoneal tumors in a murine model of
      breast cancer metastasis were identified using OPAL after systemic administration
      of a tumor-selective fluorescent molecular probe. These initial results clearly
      show that OPAL can enhance adoption and ease-of-use of fluorescence imaging in
      oncologic procedures relative to existing state-of-the-art intraoperative imaging
      systems.

PMID- 24284473
TI  - Measuring youth exposure to alcohol marketing on social networking sites:
      challenges and prospects.
AB  - Youth exposure to alcohol marketing has been linked to increased alcohol
      consumption and problems. On relatively new and highly interactive social
      networking sites (SNS) that are popular with youth, tools for measuring youth
      exposure to alcohol marketing in traditional media are inadequate. We critically
      review the existing policies of Facebook, Twitter, and YouTube designed to keep
      branded alcohol content away from underage youth. Looking at brand and user
      activity on Facebook for the 15 alcohol brands most popular among US youth, we
      found activity has grown dramatically in the past 3 years, and underage users may
      be accounting for some of this activity. Surveys of youth and adult participation
      in alcohol marketing on SNS will be needed to inform debate over these marketing
      practices. 

PMID- 24284474
TI  - Highly tunable aptasensing microarrays with graphene oxide multilayers.
AB  - A highly tunable layer-by-layer (LbL)-assembled graphene oxide (GO) array has
      been devised for high-throughput multiplex protein sensing. In this array, the
      fluorescence of different target-bound aptamers labeled with dye is efficiently
      quenched by GO through fluorescence resonance energy transfer (FRET), and
      simultaneous multiplex target detection is performed by recovering the quenched
      fluorescence caused by specific binding between an aptamer and a protein. Thin GO
      films consisting of 10 bilayers displayed a high quenching ability, yielding over
      85% fluorescence quenching with the addition of a 2 MUM dye-labeled aptamer. The
      limit for human thrombin detection in the 6- and 10-bilayered GO array is
      estimated to be 0.1 and 0.001 nM, respectively, indicating highly tunable nature
      of LbL assembled GO multilayers in controlling the sensitivity of graphene-based
      FRET aptasensor. Furthermore, the GO chip could be reused up to four times simply
      by cleaning it with distilled water.

PMID- 24284475
TI  - Dimethyltryptamine (DMT): prevalence, user characteristics and abuse liability in
      a large global sample.
AB  - This paper presents original research on prevalence, user characteristics and
      effect profile of N,N-dimethyltryptamine (DMT), a potent hallucinogenic which
      acts primarily through the serotonergic system. Data were obtained from the
      Global Drug Survey (an anonymous online survey of people, many of whom have used
      drugs) conducted between November and December 2012 with 22,289 responses.
      Lifetime prevalence of DMT use was 8.9% (n=1980) and past year prevalence use was
      5.0% (n=1123). We explored the effect profile of DMT in 472 participants who
      identified DMT as the last new drug they had tried for the first time and
      compared it with ratings provided by other respondents on psilocybin (magic
      mushrooms), LSD and ketamine. DMT was most often smoked and offered a strong,
      intense, short-lived psychedelic high with relatively few negative effects or
      "come down". It had a larger proportion of new users compared with the other
      substances (24%), suggesting its popularity may increase. Overall, DMT seems to
      have a very desirable effect profile indicating a high abuse liability that maybe
      offset by a low urge to use more. 

PMID- 24284476
TI  - The flavonoid apigenin delays forgetting of passive avoidance conditioning in
      rats.
AB  - The present experiments were performed to study the effect of the flavonoid
      apigenin (20 mg/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h
      retention performance and forgetting of a step-through passive avoidance task, in
      young male Wistar rats. There were no differences between saline- and apigenin
      treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent
      the amnesia induced by scopolamine (1mg/kg, i.p., 30 min before the acquisition).
      The saline- and apigenin-treated rats that did not step through into the dark
      compartment during the cut-off time (540 s) were retested weekly for up to eight
      weeks. In the saline treated group, the first significant decline in passive
      avoidance response was observed at four weeks, and complete memory loss was found
      five weeks after the acquisition of the passive avoidance task. At the end of the
      experimental period, 60% of the animals treated with apigenin still did not step
      through. These data suggest that 1) apigenin delays the long-term forgetting but
      did not modulate the 24 h retention of fear memory and 2) the obtained beneficial
      effect of apigenin on the passive avoidance conditioning is mediated by
      mechanisms that do not implicate its action on the muscarinic cholinergic system.

PMID- 24284477
TI  - Metal nanoparticles and DNA co-functionalized single-walled carbon nanotube gas
      sensors.
AB  - Metal/DNA/SWNT hybrid nanostructure-based gas sensor arrays were fabricated by
      means of ink jet printing of metal ion chelated DNA/SWNTs on microfabricated
      electrodes, followed by electroless deposition to reduce metal ions to metal. DNA
      served as a dispersing agent to effectively solubilize pristine SWNTs in water
      and as metal ion chelating centers for the formation of nanoparticles. Noble
      metals including palladium, platinum, and gold were used because the high binding
      affinity toward specific analytes enhances the selectivity and sensitivity. The
      sensitivity and selectivity of the gas sensors toward various gases such as H2,
      H2S, NH3, and NO2 were determined at room temperature. Sensing results indicated
      the enhancement of the sensitivity and selectivity toward certain analytes by
      functionalizing with different metal nanoparticles (e.g., Pd/DNA/SWNTs for H2 and
      H2S). The combined responses give a unique pattern or signature for each analyte
      by which the system can identify and quantify an individual gas. 

PMID- 24284478
TI  - Intragastric gelation of whey protein-pectin alters the digestibility of whey
      protein during in vitro pepsin digestion.
AB  - The aim of this work is to investigate the effect of pectin on in vitro digestion
      of whey protein. Digestion of heated whey protein isolate (WPI) and pectin
      solutions (WPI-pectin) as influenced by pectin concentration and pH was studied
      under simulated gastric conditions. Electrophoresis, dynamic light scattering,
      colorimetric measurements, and gel microstructures were used to study the
      digestion pattern. At low pectin concentration (0.25% w/w), pectin did not
      significantly influence the degradation of whey protein. Increasing the pectin
      concentration to 1% led to extensive intragastric gelation immediately after
      mixing with simulated gastric fluid. The microstructure of intragastric gel from
      WPI-pectin at pH 6.0 showed a more interconnected and denser gel network than
      that at pH 7.0. More protein and pectin were involved in the gelation at pH 6.0
      than pH 7.0. The digesta of samples at pH 6.0 was mainly composed of peptides,
      while that at pH 7.0 mostly consisted of aggregates and crosslinked peptides.
      This study suggests that WPI-pectin at high biopolymer ratio formed intragastric
      gel in simulated gastric models, which could delay protein digestion and
      potentially slow gastric emptying and promote satiety. 

PMID- 24284480
TI  - Synthesis of 3,4-dibenzyltetrahydrofuran lignans (9,9'-epoxylignanes).
AB  - Different strategies for the racemic or enantiospecific total syntheses of plant
      and mammalian 3,4-dibenzyltetrahydrofuran lignans are reviewed and compared. The
      multi-step approaches have various key step strategies: Diels-Alder reactions,
      Stobbe condensations, Michael additions, alkylations, nitrile oxide
      cycloadditions, radical cyclisations, dianion and oxidative couplings. 

PMID- 24284479
TI  - Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance
      candidate.
AB  - Phospho-sulindac (P-S), a promising anticancer agent, is efficacious in pre
      clinical models of human cancer and is apparently safe. Here, we studied the
      effect of P-S on pancreatic cancer growth. We found that P-S strongly inhibits
      the growth of human pancreatic cancer cells in vitro, is efficacious in
      inhibiting the growth of pancreatic xenografts in nude mice, and has an excellent
      safety profile. Microarray analysis revealed that P-S induced the expression of
      nuclear factor of activated T-cells, isoform c1 (NFATc1) gene. NFATc1, a
      calcineurin-responsive transcription factor associated with aggressive pancreatic
      cancer. The role of increased NFATc1 expression on the growth inhibitory effect
      of P-S on cancer growth was evaluated by silencing or by overexpressing it both
      in vitro and in vivo. We found that when the expression of NFATc1 was abrogated
      by RNAi, pancreatic cancer cells were more responsive to treatment with P-S.
      Conversely, overexpressing the NFATc1 gene made the pancreatic cancer cells less
      responsive to treatment with P-S. NFATc1 likely mediates drug resistance to P-S
      and is an unfavorable prognostic factor that predicts poor tumor response. We
      also demonstrated that NFATc1-mediated resistance can be overcome by cyclosporin
      A (CsA), an NFAT inhibitor, and that the combination of P-S and CsA
      synergistically inhibited pancreatic cancer cell growth. In conclusion, our
      preclinical data establish P-S as an efficacious drug for pancreatic cancer in
      preclinical models, which merits further evaluation.

PMID- 24284481
TI  - Polyethylene glycol (PEG-400): an efficient and recyclable reaction medium for
      the synthesis of pyrazolo[3,4-b]pyridin-6(7H)-one derivatives.
AB  - A mild and efficient synthesis of pyrazolo[3,4-b]pyridine-6(7H)-one derivatives
      via a three-component reaction of an aldehyde, Meldrum's acid and 3-methyl-1H
      pyrazol-5-amine using recyclable polyethylene glycol (PEG)-400 as a reaction
      medium is described. This method has the advantages of accessible starting
      materials, good yields, mild reaction conditions and begin environmentally
      friendly. 

PMID- 24284482
TI  - Peptide conjugation via CuAAC 'click' chemistry.
AB  - The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or
      'click' reaction, is a highly versatile reaction that can be performed under a
      variety of reaction conditions including various solvents, a wide pH and
      temperature range, and using different copper sources, with or without additional
      ligands or reducing agents. This reaction is highly selective and can be
      performed in the presence of other functional moieties. The flexibility and
      selectivity has resulted in growing interest in the application of CuAAC in
      various fields. In this review, we briefly describe the importance of the
      structural folding of peptides and proteins and how the 1,4-disubstituted
      triazole product of the CuAAC reaction is a suitable isoster for an amide bond.
      However the major focus of the review is the application of this reaction to
      produce peptide conjugates for tagging and targeting purpose, linkers for
      multifunctional biomacromolecules, and reporter ions for peptide and protein
      analysis. 

PMID- 24284483
TI  - Physiological effects of L-theanine on Drosophila melanogaster.
AB  - Green tea has been consumed as the most popular drink in East Asia for centuries,
      and is believed to have a wide range of health benefits. L-Theanine, the major
      component of the free amino acids in green tea, has been reported to display
      neuronal protection and tumor inhibition in vitro, but its physiological effects
      on animal development and behavior remain elusive. In this report, we used
      Drosophila melanogaster, the fruit fly, as a model organism to investigate the
      physiological effects of L-theanine. Flies were fed with three different
      concentrations of theanine as a dietary supplement after eclosion, and were
      examined for a variety of physiological parameters at different time points. We
      found theanine treatment results in significantly increased locomotion and
      courtship ability, and decreased resistance against wet and dry starvation in
      males, but not in females. Furthermore, theanine application diminished UV
      tolerance in females, but not in males. However, we did not perceive
      distinguishable effect of theanine on animal development, life span, weight, and
      tolerance of heat and anoxia. This work represents the first comprehensive
      physiological investigation of L-theanine at the whole animal level, and shall
      shed light on the mechanistic study of theanine in the future.

PMID- 24284484
TI  - Following the mechanisms of bacteriostatic versus bactericidal action using Raman
      spectroscopy.
AB  - Antibiotics cure infections by influencing bacterial growth or viability.
      Antibiotics can be divided to two groups on the basis of their effect on
      microbial cells through two main mechanisms, which are either bactericidal or
      bacteriostatic. Bactericidal antibiotics kill the bacteria and bacteriostatic
      antibiotics suppress the growth of bacteria (keep them in the stationary phase of
      growth). One of many factors to predict a favorable clinical outcome of the
      potential action of antimicrobial chemicals may be provided using in vitro
      bactericidal/bacteriostatic data (e.g., minimum inhibitory concentrations-MICs).
      Consequently, MICs are used in clinical situations mainly to confirm resistance,
      and to determine the in vitro activities of new antimicrobials. We report on the
      combination of data obtained from MICs with information on microorganisms'
      "fingerprint" (e.g., DNA/RNA, and proteins) provided by Raman spectroscopy. Thus,
      we could follow mechanisms of the bacteriostatic versus bactericidal action
      simply by detecting the Raman bands corresponding to DNA. The Raman spectra of
      Staphylococcus epidermidis treated with clindamycin (a bacteriostatic agent)
      indeed show little effect on DNA which is in contrast with the action of
      ciprofloxacin (a bactericidal agent), where the Raman spectra show a decrease in
      strength of the signal assigned to DNA, suggesting DNA fragmentation. 

PMID- 24284485
TI  - Genistein enhances the radiosensitivity of breast cancer cells via G2/M cell
      cycle arrest and apoptosis.
AB  - The aim of the present study was to investigate the radiosensitizing effect of
      genistein, and the corresponding mechanisms of action on breast cancer cells with
      different estrogen receptor (ER) status. Human breast cancer cell lines such as
      MCF-7 (ER-positive, harboring wild-type p53) and MDA-MB-231 (ER-negative,
      harboring mutant p53) were irradiated with X-rays in the presence or absence of
      genistein. Cell survival, DNA damage and repair, cell cycle distribution, cell
      apoptosis, expression of proteins related to G2/M cell cycle checkpoint and
      apoptosis were measured with colony formation assays, immunohistochemistry, flow
      cytometry and western blot analysis, respectively. Genistein showed relatively
      weak toxicity to both cell lines at concentrations in the range of 5-20 MUM.
      Using the dosage of 10 MUM genistein, the sensitizer enhancement ratios after
      exposure to X-rays at a 10% cell survival (IC10) were 1.43 for MCF-7 and 1.36 for
      MDA-MB-231 cells, respectively. Significantly increased DNA damages, arrested
      cells at G2/M phase, decreased homologous recombination repair protein Rad51 foci
      formation and enhanced apoptotic rates were observed in both cell lines treated
      by genistein combined with X-rays compared with the irradiation alone. The
      combined treatment obviously up-regulated the phosphorylation of ATM, Chk2,
      Cdc25c and Cdc2, leading to permanent G2/M phase arrest, and up-regulated Bax and
      p73, down-regulated Bcl-2, finally induced mitochondria-mediated apoptosis in
      both cell lines. These results suggest that genistein induces G2/M arrest by the
      activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway and ultimately enhances
      the radiosensitivity of both ER+ and ER- breast cancer cells through a
      mitochondria-mediated apoptosis pathway.

PMID- 24284486
TI  - Deep oxidative desulfurization of dibenzothiophene in simulated oil and real
      diesel using heteropolyanion-substituted hydrotalcite-like compounds as
      catalysts.
AB  - Three heteropolyanion substituted hydrotalcite-like compounds (HPA-HTLcs)
      including Mg9Al3(OH)24[PW12O40](MgAl-PW12), Mg9Al3(OH)24[PMo12O40] (MgAl-PMo12)
      and Mg12Al4(OH)32[SiW12O40] (MgAl-SiW12), were synthesized, characterized and
      used as catalysts for the oxidative desulfurization of simulated oil
      (dibenzothiophene, DBT, in n-octane). MgAl-PMo12 was identified as an effective
      catalyst for the oxidative removal of DBT under very mild conditions of
      atmospheric pressure and 60  degrees C in a biphasic system using hydrogen
      peroxide as oxidant and acetonitrile as extractant. The conversion of DBT was
      nearly 100%. As a result, because of the influence of the electron density and
      the space steric hindrance, the oxidation reactivity of the different sulfur
      compounds in simulated oil followed the order DBT > 4,6-dimethyldibenzothiophene
      (4,6-DMDBT) > benzothiophene (BT) > thiophene (TH). When the reaction is
      finished, the catalysts can be recovered from the acetonitrile phase by
      filtration. The recovered MgAl-PMo12 retains nearly the same catalytic activity
      as the fresh material. Moreover, MgAl-PMo12 was found to exhibit an ideal
      catalytic activity in the oxidative desulfurization of real diesel resulting in a
      total remaining sulfur content of 9.12 ppm(w).

PMID- 24284487
TI  - A comparative study of ferulic acid on different monosaccharide-mediated protein
      glycation and oxidative damage in bovine serum albumin.
AB  - Three dietary monosaccharides, (glucose, fructose, and ribose), have different
      rates of protein glycation that accelerates the production of advanced glycation
      end-products (AGEs). The present work was conducted to investigate the effect of
      ferulic acid (FA) on the three monosaccharide-mediated protein glycations and
      oxidation of BSA. Comparing the percentage reduction, FA (1-5 mM) reduced the
      level of fluorescence AGEs (F-AGEs) and N(epsilon)-(carboxymethyl) lysine
      (N(epsilon)-CML) in glucose-glycated BSA (F-AGEs = 12.61%-36.49%; N(epsilon)-CML
      = 33.61%-66.51%), fructose-glycated BSA (F-AGEs = 25.28%-56.42%; N(epsilon)-CML =
      40.21%-62.91%), and ribose-glycated BSA (F-AGEs = 25.63%-51.18%; N(epsilon)-CML =
      26.64%-64.08%). In addition, the percentages of FA reduction of fructosamine
      (Frc) and amyloid cross beta-structure (Amy) were Frc = 20.45%-43.81%; Amy =
      17.84%-34.54% in glucose-glycated BSA, Frc = 25.17%-36.92%; Amy = 27.25%-39.51%
      in fructose-glycated BSA, and Frc = 17.34%-29.71%; Amy = 8.26%-59.92% in ribose
      glycated BSA. FA also induced a reduction in protein carbonyl content (PC) and
      loss of protein thiol groups (TO) in glucose-glycated BSA (PC = 37.78%-56.03%; TO
      = 6.75%-13.41%), fructose-glycated BSA (PC = 36.72%-52.74%; TO = 6.18%-20.08%),
      and ribose-glycated BSA (PC = 25.58%-33.46%; TO = 20.50%-39.07%). Interestingly,
      the decrease in fluorescence AGEs by FA correlated with the level of N(epsilon)
      CML, fructosamine, amyloid cross beta-structure, and protein carbonyl content.
      Therefore, FA could potentially be used to inhibit protein glycation and
      oxidative damage caused by monosaccharides, suggesting that it might prevent AGEs
      mediated pathologies during diabetic complications.

PMID- 24284488
TI  - A bicyclic diterpenoid with a new 15,16-dinorlabdane carbon skeleton from
      Leonurus japonicus and its coagulant bioactivity.
AB  - A new 15,16-dinorlabdane diterpenoid 1 and a known labdane diterpenoid 2,
      together with three known ergosterols 3-5, were isolated from the EtOAc-soluble
      portion of the EtOH extract of Leonurus japonicus. Their structures were
      elucidated by physical and spectroscopic analysis. Compound 1 showed in vitro
      coagulant activity in the APTT, PT, TT, and FIB assays. 

PMID- 24284489
TI  - The Henry reaction in [Bmim][PF6]-based microemulsions promoted by acylase.
AB  - An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was
      first studied using water-in-[Bmim][PF6] microemulsions as reaction medium. The
      Amano acylase from Aspergillus oryzae showed better catalytic activity for the
      addition reactions of nitromethane with a series of aromatic aldehydes, and a
      highest yield of 90% was obtained. 

PMID- 24284490
TI  - An in vitro study of the antimicrobial effects of indigo naturalis prepared from
      Strobilanthes formosanus Moore.
AB  - Indigo naturalis is effective in treating nail psoriasis coexisting with
      microorganism infections. This study examines the antimicrobial effects of indigo
      naturalis prepared from Strobilanthes formosanus Moore. Eight bacterial and seven
      fungal strains were assayed using the agar diffusion method to examine the
      effects of indigo naturalis and its bioactive compounds. The bioactive compounds
      of indigo naturalis were purified sequentially using GFC, TLC, and HPLC. Their
      structures were identified using mass spectrometry and NMR spectroscopy. UPLC
      MS/MS was applied to compare the metabolome profiles of indigo naturalis ethyl
      acetate (EA) extract and its source plant, Strobilanthes formosanus Moore. The
      results of in vitro antimicrobial assays showed that indigo naturalis EA-extract
      significantly (>=1 mg/disc) inhibits Gram-positive bacteria (Staphylococcus
      aureus, S. epidermis and methicillin-resistant S. aureus (MRSA)) and mildly
      inhibits non-dermatophytic onychomycosis pathogens (Aspergillus fumigates and
      Candida albicans), but has little effect on dermatophyes. Isatin and tryptanthrin
      were identified as the bioactive compounds of indigo naturalis using S. aureus
      and S. epidermis as the bioassay model. Both bioactive ingredients had no effect
      on all tested fungi. In summary, indigo naturalis prepared from Strobilanthes
      formosanus Moore exhibits antimicrobial effects on Staphylococcus and non
      dermatophytic onychomycosis pathogens. Tryptanthrin and isatin may be its major
      bioactive ingredients against Staphylococcus and the inhibitory effect on MRSA
      may be due to other unidentified ingredients. 

PMID- 24284491
TI  - Biological activity of propolis-honey balm in the treatment of experimentally
      evoked burn wounds.
AB  - Medicines of biogenic origin with micro-organic, regenerative and analgesic
      properties are becoming more and more significant in the treatment of burn
      wounds. These properties are found in apitherapeutics such as propolis and honey-
      products collected and processed by a honey bee. Their effect on the course of
      the healing processes is multidirectional. The aim of the study was a
      histopathological and biochemical analysis of the processes of scar formation in
      experimentally evoked burn wounds in white pigs treated with the 1% and 3%
      Sepropol balms containing standardized extracts of propolis and honey. The
      results were compared with the therapeutic effects obtained with dermazin cream
      (1% silver sulfadiazine). The level of collagen was determined in the wounds
      treated with 1% and 3% Sepropol and compared with the collagen level in healthy
      skin and wounds treated with dermazin. Granulation and regenerated epithelium
      formation times were compared, with the 3% Sepropol being by far the most
      effective. The 3% Sepropol also increased the collagen level to 116% with the
      control sub-groups scoring between 80% and 98%. The results show the healing
      process of burn wounds in pigs treated with the Sepropol balm starts earlier and
      has a faster course than the standard dermazin therapy.

PMID- 24284492
TI  - Solution structure of the circular gamma-domain analog from the wheat
      metallothionein E(c)-1.
AB  - The first cyclic analog of a metallothionein (MT) was prepared and analyzed by UV
      and (magnetic) circular dichroism spectroscopy, ESI-MS as well as NMR
      spectroscopy. Results reveal that the evaluated cyclic gamma-E(c)-1 domain of the
      wheat MT E(c)-1 retains its ability to coordinate two Zn(II) or Cd(II) ions and
      adopts a three-dimensional structure that is highly similar to the one of the
      linear wild-type form. However, the reduced flexibility of the protein backbone
      facilitates structure solution significantly and results in a certain
      stabilization of metal binding to the protein.

PMID- 24284493
TI  - Deracemization of axially chiral nicotinamides by dynamic salt formation with
      enantiopure dibenzoyltartaric acid (DBTA).
AB  - Dynamic atroposelective resolution of chiral salts derived from oily racemic
      nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by
      crystallization. The absolute structures of the axial chiral nicotinamides were
      determined by X-ray structural analysis. The chirality could be controlled by the
      selection of enantiopure DBTA as a chiral auxiliary. The axial chirality
      generated by dynamic salt formation was retained for a long period after
      dissolving the chiral salt in solution even after removal of the chiral acid. The
      rate of racemization of nicotinamides could be controlled based on the
      temperature and solvent properties, and that of the salts was prolonged compared
      to free nicotinamides, as the molecular structure of the pyridinium ion in the
      salts was different from that of acid-free nicotinamides. 

PMID- 24284494
TI  - Determination and comparison of seed oil triacylglycerol composition of various
      soybeans (Glycine max (L.)) using 1H-NMR spectroscopy.
AB  - Seed oil triacylglycerol (TAG) composition of 32 soybean varieties were
      determined and compared using 1H-NMR. The contents of linolenic (Ln), linoleic
      (L), and oleic (O) ranged from 10.7% to 19.3%, 37.4%-50.1%, and 15.7%-34.1%,
      respectively. As is evident, linoleic acid was the major fatty acid of soybean
      oil. Compositional differences among the varieties were observed. Natural oils
      containing unsaturated groups have been regarded as important nutrient and
      cosmetic ingredients because of their various biological activities. The TAG
      profiles of the soy bean oils could be useful for distinguishing the origin of
      seeds and controlling the quality of soybean oils. To the best of our knowledge,
      this is the first study in which the TAG composition of various soybean oils has
      been analyzed using the 1H-NMR method.

PMID- 24284495
TI  - Swelling-activated Cl- currents and intracellular CLC-3 are involved in
      proliferation of human pulmonary artery smooth muscle cells.
AB  - BACKGROUND: Proliferation of pulmonary artery smooth muscle cells (PASMCs) leads
      to adverse vascular remodeling and contributes to pulmonary arterial
      hypertension, a condition associated with a 15% annual mortality despite
      treatment. We previously showed that swelling-activated Cl currents (ICl,swell)
      are upregulated in PASMC proliferation and that nonspecific Cl current blockers
      inhibit proliferation. However, the specific role of ICl,swell in PASMC
      proliferation and its molecular underpinning remain unknown. METHODS AND RESULTS:
      In the present study, we found that the specific ICl,swell blocker, DCPIB (4-[(2
      butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy] butanoic
      acid), dose-dependently blocked (IC50 = 2.7 MUmol/l) ICl,swell and inhibited
      (IC50 = 6.9 MUmol/l) proliferation in isolated human PASMCs (hPASMCs). To
      identify the Cl channel genes underlying ICl,swell and regulating hPASMC
      proliferation, we measured the mRNA expression of candidate Cl channel genes (CLC
      1 to CLC-7, CLC-Ka and CLC-Kb, and BEST-1 to BEST-4) in hPASMCs. CLC-2 to CLC-7
      and BEST-1 are expressed in hPASMCs, with the most abundant gene being CLC-3, a
      channel gene previously linked to ICl,swell. Although stable expression of a
      microRNA-adapted shRNA targeting CLC-3 transcripts in hPASMCs selectively reduced
      CLC-3 mRNA by more than 80% and inhibited hPASMC proliferation (by >45%) compared
      with control-shRNA, it did not alter ICl,swell. Consistent with this observation,
      immunocytostaining studies revealed that CLC-3 protein is primarily located in
      intracellular areas of cultured proliferative hPASMCs. The intracellular CLC-3
      protein levels were profoundly reduced by shRNA targeting CLC-3. The other
      molecular candidate for ICl,swell (i.e.,CLC-2) also showed a mainly intracellular
      distribution. CONCLUSION: Our findings support the conclusion that both ICl,swell
      and CLC-3 play a role in PASMC proliferation, but CLC-3 channels do not underlie
      ICl,swell in these cells.

PMID- 24284496
TI  - HY-Quest, standardized patient questionnaire to be completed at home before a
      first visit for hypertension: a validation study in specialized centres in
      France.
AB  - OBJECTIVE: To evaluate a patient questionnaire (HY-QUEST) to be completed at home
      before consulting in a hypertension clinic for the first time. METHODS: HY-QUEST
      is a questionnaire translated into patient language of the items from a
      standardized computerized medical record used since 1975 and regularly updated.
      This questionnaire contains 97 closed and seven free-text questions designed to
      evaluate cardiovascular risk and possible secondary hypertension, and to guide
      therapeutic strategy. One hundred and thirty-three new patients were asked to
      complete it at home and to bring it with them to their first visit in the
      hypertension clinic. The primary end-point was completeness of the answers. Other
      end-points were legibility and correctness of the answers. RESULTS:
      Questionnaires were available for 128 out of 133 patients (96%). More than 80% of
      the 97 closed questions were answered in 121 out of 128 questionnaires [94.6%;
      95% confidence interval (CI) 90.7-98.5] and no question had a response rate less
      than 85%. The answers were legible in 85% of the closed questions and the
      concordance rate with the physician's assessment was 94%. Among the 101 treated
      patients, 72 (71.3%; 95% CI 62.5-80.1) were able to provide the correct names,
      doses and schedule of their antihypertensive treatments. CONCLUSION: The HY-QUEST
      questionnaire can be completed by most patients with few missing or incorrect
      answers. It is well accepted by patients and provides useful information to
      orient the first consultation in a hypertension clinic. Whether the same approach
      is feasible and useful in primary care remains to be investigated.

PMID- 24284497
TI  - Genetic variation in NEDD4L, an epithelial sodium channel regulator, is
      associated with cardiovascular disease and cardiovascular death.
AB  - OBJECTIVES: We have previously shown that genetic variance in NEDD4L, a
      regulating protein of a sodium channel in the distal nephron, has been associated
      with marginally higher blood pressure and enhanced salt sensitivity. Here, we
      tested if the genetic NEDD4L variation previously associated with salt
      sensitivity is related to population blood pressure, incidence of cardiovascular
      disease (CVD) and mortality. METHOD: We genotyped the rs4149601 A->G and
      rs2288774 T->C NEDD4L variants in 27,564 participants of the Malmo Diet and
      Cancer Study. The genotype combination previously shown to be associated with
      salt sensitivity (rs4149601 GG+rs2288774 CC), which was present in 9.6% of
      participants, was related to cross sectional blood pressure as well as to CVD
      incidence and mortality during a median follow-up time of 14 years using Cox
      regression models. RESULTS: Carriers of the NEDD4L salt sensitivity-associated
      genotype had (mean +/- SEM) higher systolic (142 +/- 0.4 vs. 141 +/- 0.1 mmHg, P
      = 0.002) and diastolic (86.0 +/- 0.5 vs. 85.6 +/- 0.2 mmHg, P = 0.025) blood
      pressure and multivariate adjusted hazards ratio (95% confidence interval) of CVD
      1.13 (1.02-1.25, P = 0.018), coronary events 1.20 (1.06-1.37; P = 0.005) and
      cardiovascular mortality 1.17 (0.99-1.37; P = 0.055) than noncarriers but there
      was no significant difference in the incidence of stroke and total mortality.
      CONCLUSION: The NEDD4L salt sensitivity-associated genotype was associated with
      higher blood pressure, which may translate into increased risk for CVD morbidity
      and mortality. Interestingly, there was no association with stroke suggesting
      that the association is partially blood pressure independent.

PMID- 24284498
TI  - Dietary sodium influences the effect of mental stress on heart rate variability:
      a randomized trial in healthy adults.
AB  - BACKGROUND: Dietary sodium influences intermediate physiological traits in
      healthy adults independent of changes in blood pressure. The purpose of this
      study was to test the hypothesis that dietary sodium affects cardiac autonomic
      modulation during mental stress. METHOD: In a prospective, randomized cross-over
      design separated by 1 month between diets, 70 normotensive healthy young adults
      (F/M: 44/26, aged 18-38 years) consumed a 5-day low (10 mmol/day), normal (150
      mmol), and high (400 mmol) sodium diet followed by heart rate variability (HRV)
      recordings at rest and during 5-min computerized mental arithmetic. Women were
      studied in the low hormone phase of the menstrual cycle following each diet.
      RESULTS: Diet did not affect resting blood pressure, but heart rate (HR) (mean +/
      SE) was 66 +/- 1, 64 +/- 1, and 63 +/- 1 bpm in low, normal, and high sodium
      conditions, respectively (analysis of variance P = 0.02). For HRV, there was a
      main effect of sodium on resting SD of normalized RR intervals (SDNN), square
      root of the mean squared difference of successive normalized RR intervals
      (RMSSD), high frequency, low-frequency normalized units (LFnu), and high
      frequency normalized units (HFnu) (P < 0.01 for all). The response to low sodium
      was most marked and consistent with sympathetic activation and reduced vagal
      activity, with increased LFnu and decreased SDNN, RMSSD, and HFnu compared to
      both normal and high sodium conditions (P <=0.05 for all). Dietary sodium-by
      mental stress interactions were significant for mean NN, RMSSD, high-frequency
      power, LFnu, and low frequency/high frequency ratio (P < 0.05 for all). The
      interactions signify that sodium restriction evoked an increase in resting
      sympathetic activity and reduced vagal activity to the extent that mental stress
      caused modest additional disruptions in autonomic balance. Conversely, normal and
      high sodium evoked a reduction in resting sympathetic activity and incremental
      increase in resting vagal activity, which were disrupted to a greater extent
      during mental stress compared to low sodium. CONCLUSION: We conclude that
      autonomic control of HRV at rest and during mental stress is altered by dietary
      sodium in healthy normotensive young adult men and women.

PMID- 24284499
TI  - Effect of intensified diuretic therapy on overnight rostral fluid shift and
      obstructive sleep apnoea in patients with uncontrolled hypertension.
AB  - OBJECTIVES: Fluid displacement from the lower extremities to the upper body
      during sleep is strongly associated with obstructive sleep apnoea in hypertensive
      patients. The present pathophysiological study tests the hypothesis that
      intensified diuretic therapy will reduce the apnoea-hypopnoea index and blood
      pressure of uncontrolled hypertensive patients with obstructive sleep apnoea in
      proportion to the reduction in overnight change in leg fluid volume. METHODS:
      Uncontrolled treated hypertensive patients underwent overnight polysomnography
      and measurement of overnight changes in leg fluid volume and neck circumference.
      Those with an apnoea-hypopnoea index at least 20 events per hour (n=16) received
      metolazone 2.5 mg and spironolactone 25 mg daily for 7 days after which the daily
      dose was doubled for 7 additional days. Baseline testing was again repeated.
      RESULTS: Intensified diuretic therapy reduced the apnoea-hypopnoea index from
      57.7 +/- 33.0 to 48.5 +/- 28.2 events per hour (P=0.005), overnight change in leg
      fluid volume from -418.1 +/- 177.5 to -307.5 +/- 161.9 ml (P<0.001) and overnight
      change in neck circumference from 1.2 +/- 0.6 to 0.7 +/- 0.4 cm (P<0.001). There
      was an inverse correlation between the reduction in overnight change in leg fluid
      volume and decrease in apnoea-hypopnoea index (r=-0.734, P=0.001). The reduction
      in overnight change in leg fluid volume was also significantly correlated with
      the change in morning blood pressure (r=0.708, P=0.002 for SBP; r=0.512, P=0.043
      for DBP). CONCLUSION: The findings provide further evidence that fluid
      redistribution from the legs to the neck during sleep contributes to the severity
      of obstructive sleep apnoea in hypertension and may be an important link between
      these two conditions.

PMID- 24284500
TI  - Interarm blood pressure difference and target organ damage in the general
      population.
AB  - OBJECTIVE: The objective of the study was to investigate interarm differences of
      blood pressure (BP) and its determinants, and to clarify whether both arms are
      equally good in assessing BP and target organ damage in the general population.
      METHODS: We studied a representative sample of Finnish adult population with 484
      study participants, ages 25-74 years. BP was measured twice by an oscillometric
      monitor simultaneously on both arms. Study participants underwent a clinical
      examination including measurements of serum lipids, glucose and indicators of
      target organ damage. RESULTS: BP was 2.3/0.2 mmHg higher on right than on left
      arm (P < 0.001/P = 0.15 for SBP/DBP differences). SBP and DBP measured on right
      and left arms correlated equally with left ventricular mass index (LVMI),
      interventricular septal thickness (IVST), posterior wall thickness (PWT), pulse
      wave velocity (PWV) and albuminuria. Higher SBP level was an independent
      determinant of both greater systolic and diastolic interarm BP difference.
      Exaggerated absolute diastolic interarm BP difference (>5 mmHg) was associated
      with higher BMI, arm circumference, LVMI, IVST and PWT, whereas exaggerated
      absolute systolic interarm BP difference (>10 mmHg) was not associated with any
      clinical variables. CONCLUSION: There was only a small difference in BP between
      arms in a healthy general population. Both arms are equally good determinants of
      target organ damage. BP should be measured at least once on both arms and prefer
      the arm with higher BP readings in the future BP measurements.

PMID- 24284501
TI  - The madness of Gerard de Nerval.
AB  - This paper examines the madness of Gerard de Nerval, the nineteenth-century
      French writer. It looks at his account of mental disturbance, how he responded to
      the psychiatric profession and how he reacted to being diagnosed as insane. It
      considers his autobiographical novella of madness, Aurelia, which he began at the
      suggestion of his alienist, Dr Emile Blanche, and while he was still an asylum
      inmate. Nerval's story raises important questions about the nature of madness. Is
      it, as he contended, a mystical experience revealing truths about spiritual
      worlds inaccessible to the 'sane'? Does psychiatry fail to understand it and
      inappropriately reduce it to the categories of scientific reason? Or are such
      notions of the spiritual value of madness guilty of the charge that they
      romanticise insanity? Do they make extravagant claims for an experience that is
      often disturbing and debilitating? What is the relationship between madness and
      recovery? Should an individual try to forget their experience of mental
      disturbance once they recover, or should they examine what the event reveals
      about themselves? Can the language of madness be decoded to unveil profound
      truths as Carl Jung and R.D. Laing have suggested, or is it, as the psychiatrist
      German Berrios maintains, merely a series of 'empty speech acts', signifying
      nothing? And finally, how does one avoid writing about madness, and instead write
      madness? 

PMID- 24284502
TI  - What factors predict recurrence after an initial episode of primary spontaneous
      pneumothorax in children?
AB  - PURPOSE: Recurrence is the most common complication after an initial episode of
      primary spontaneous pneumothorax (PSP). However, preventive surgery in children
      remains a controversial issue. The purpose of this study was to determine
      predictive factors of recurrence to better inform early surgical referrals.
      METHODS: We retrospectively reviewed all consecutive patients under 18 years of
      age who conservatively treated for an initial episode of PSP between March 2005
      and September 2011. RESULTS: One hundred fourteen patients were included in this
      study. The mean follow-up period was 43.1 months. Ipsilateral and contralateral
      recurrence developed in 47.3% and 14.0% of patients. The risk of ipsilateral
      recurrence for patients with or without air-containing lesions according to high
      resolution computed tomography (HRCT) was 60.3% and 31.4%. In the multivariate
      analysis, the presence of air-containing lesions on HRCT scans and bullae on
      chest X-rays were independent risk factors for ipsilateral recurrence.
      CONCLUSION: The presence of bleb or bullae on HRCT scans or chest X-rays after an
      initial episode of PSP was significantly related to the ipsilateral recurrence in
      children. If the risk factors are clarified in further studies, hospital stays
      and the recurrence of PSP after the first episode could be reduced with early
      video-assisted thoracoscopic surgery.

PMID- 24284503
TI  - Clinical and pathological features of degenerative mitral valve disease:
      billowing mitral leaflet versus fibroelastic deficiency.
AB  - PURPOSE: Degenerative mitral valve disease is distinguished with billowing mitral
      leaflet (BML) or fibroelastic deficiency (FED). The purpose of this study is to
      evaluate the clinical characteristics and the pathohistological differences
      between BML and FED. METHODS: A total of 73 patients who diagnosed as
      degenerative mitral valve disease pathologically after mitral valve surgery for
      severe mitral regurgitation were enrolled. On the basis of echocardiographic
      features and gross appearances, they were classified as BML (9 cases) and FED (64
      cases). RESULTS: In the BML group, multiple segments of the leaflet showed
      billowing with elongated chordae. Therefore excessive valve tissue needed to be
      removed by multiple resection and suture. The FED patients had focal myxomatous
      changes with ruptured chordae, a single resection and suture was frequently
      employed. In pathological examination, the valve thickness of the BML was nearly
      twice as thick as the FED, and the mucopolysaccharide accumulation of the
      Spongiosa in the BML was over 50%, while 30% in the FED. CONCLUSION: BML presents
      the characteristic valve thickening due to its abnormal production of
      mucopolysaccharide. Since excessive tissue was voluminous in the BML, high-grade
      plasty techniques, such as combination of multiple resection and chordal
      reconstruction were required.

PMID- 24284504
TI  - Surgical thrombectomy and simultaneous stenting for deep venous thrombosis caused
      by iliac vein compression syndrome (May-Thurner syndrome).
AB  - PURPOSE: Iliac vein compression syndrome (May-Thurner syndrome) is characterized
      by left iliac vein obstruction secondary to compression by the right common iliac
      artery against the fifth-lumbar vertebra, which increases incidence of deep
      venous thrombosis (DVT). We treated the patients with DVT due to May-Thurner
      syndrome (MTS) by surgical thrombectomy and simultaneous stenting, and this study
      is to evaluate the outcomes of this procedure. METHODS: From January 2009 to
      December 2011, a total of 8 patients underwent surgical thrombectomy with
      stenting. All patients were admitted for acute DVT involving the left iliofemoral
      segment, and diagnosed MTS. Patients were followed-up, and stent patency was
      assessed by means of duplex sonography. RESULTS: In all patients, the procedure
      was successful in achieving re-canalisation of the iliofemoral veins at the end
      of the operation. Perioperatively, there was no mortality and there was no case
      of clinically detected pulmonary embolism. Rethrombosis occurred within seven
      days of operation in 2 patients. During the follow-up period (mean; 16 months), 6
      of 8 patients kept patent stents. CONCLUSION: Venous thrombectomy with
      simultaneous stenting is a potent technique to treat acute iliofemoral DVT due to
      MTS. This technique can restore venous patency and provide relief of the acute
      symptoms.

PMID- 24284505
TI  - A history of surgery for locally-advanced (T4) cancer of the thoracic esophagus
      in Japan and a personal perspective.
AB  - The history of esophageal surgery in Japan can be divided into three periods, an
      era of safety from 1930 to 1980, an era of radicality from 1980 to 2000, and the
      era of quality of life (QOL) from 2000 to the present. The treatment for T4
      cancers of the thoracic esophagus has also changed over time from preoperative
      radiotherapy, combined resection of the neighboring organs with esophagectomy,
      and to definitive chemoradiotherapy (dCRT) with salvage surgery. At present,
      almost all patients with an unresectable T4 esophageal cancer receives dCRT.
      However, there are many patients with a residual or recurrent tumor after dCRT.
      Salvage surgery for such patients often results in incomplete resection of the
      tumor because the tumor involves the trachea and/or aorta. New techniques to
      enable the resection of such neighboring organs even during salvage surgery are
      needed. In the future, the mainstay of treatment for esophageal cancer will be
      CRT with the foreseeable progress in new drugs and new techniques of
      radiotherapy. Surgery will be indicated for a local failure after CRT, while
      combined resection of the neighboring organs will be necessary to treat a local
      failure after CRT for T4 cancers. New surgical techniques have to be developed
      through some application of new devices and equipment. 

PMID- 24284506
TI  - Thoracoscopic esophagectomy using prone positioning.
AB  - Thoracotomic esophagectomy followed by cervical and abdominal procedures has been
      conventionally performed as the best curable operative procedure for treating
      invasive thoracic esophageal carcinoma. Despite improvements in the survival
      rate, the procedure is associated with significant operative morbidity and
      mortality rates due to the extreme invasiveness of an extensive dissection of the
      lymph nodes. Minimally invasive esophagectomy (MIE) was developed to reduce
      surgical invasiveness. Recently, the use of thoracoscopic esophagectomy performed
      in the prone position has stimulated new interest in minimally invasive
      approaches. However, the advantages and disadvantages of this technique are not
      well known. In this review, the literature to date, including series and
      comparative studies of minimally invasive esophagectomy performed in the prone
      position, is summarized, and the various lessons learned and controversies
      surrounding this technique are addressed. 

PMID- 24284507
TI  - Preoperative 18F-fluorodeoxyglucose positron emission tomography can predict the
      tumor malignancy of small peripheral lung cancer.
AB  - PURPOSE: Recent advances in image diagnostic technology have enhanced the
      discovery of peripheral small size lung cancers. Here, we examined the utility of
      18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation
      of grade of tumor malignant potency. METHODS: Seventy-nine patients with
      peripheral small lung cancers (<=2 cm) who underwent surgical resections and
      preoperative FDG-PET were enrolled. The correlations between the maximum
      standardized uptake value (SUVmax) and various clinicopathological features
      related to tumor invasiveness, nodal metastasis, and recurrence were analyzed.
      RESULTS: The median SUVmax of all tumors was 2.4 (range, 0-16.1). The SUVmax was
      significantly higher in patients with vascular invasion (5.6 +/- 3.5 vs. 2.4 +/-
      2.4; P <0.0001), lymphatic invasion (4.9 +/- 3.7 vs. 2.7 +/- 2.6; P = 0.0029),
      lymph node metastasis (6.1 +/- 4.4 vs. 3.0 +/- 2.7; P = 0.0022), and recurrences
      (5.8 +/- 3.3 vs. 3.1 +/- 3.1; P = 0.0219). Patients with SUVmax >=2.5 had a
      significantly higher incidence rate of vascular invasion (56% vs. 7%; P <0.0001),
      lymphatic invasion (51% vs. 15%; P = 0.0006), lymph node metastasis (26% vs. 3%;
      P = 0.0033), and recurrence (18% vs. 3%; P = 0.0289). The patients with SUVmax
      >=1.5 also had a significantly higher incidence of vascular invasion, lymphatic
      invasion, lymph node metastasis, and recurrence. It is particularly worth noting
      that patients with SUVmax <1.5 had no vascular invasion, lymph node metastasis,
      or recurrence. CONCLUSION: Preoperative SUVmax of peripheral small lung cancers
      were significantly associated with tumor malignancy.

PMID- 24284508
TI  - Discontinuous spirals of stable periodic oscillations.
AB  - We report the experimental discovery of a remarkable organization of the set of
      self-generated periodic oscillations in the parameter space of a nonlinear
      electronic circuit. When control parameters are suitably tuned, the wave pattern
      complexity of the periodic oscillations is found to increase orderly without
      bound. Such complex patterns emerge forming self-similar discontinuous phases
      that combine in an artful way to produce large discontinuous spirals of
      stability. This unanticipated discrete accumulation of stability phases was
      detected experimentally and numerically in a Duffing-like proxy specially
      designed to bypass noisy spectra conspicuously present in driven oscillators.
      Discontinuous spirals organize the dynamics over extended parameter intervals
      around a focal point. They are useful to optimize locking into desired
      oscillatory modes and to control complex systems. The organization of
      oscillations into discontinuous spirals is expected to be generic for a class of
      nonlinear oscillators. 

PMID- 24284509
TI  - MiR-223 downregulation promotes glomerular endothelial cell activation by
      upregulating importin alpha4 and alpha5 in IgA nephropathy.
AB  - Glomerular endothelial cells (GEnCs) contribute to renal injuries in IgA
      nephropathy (IgAN). Here we profiled microRNAs (miRNAs) in GEnCs treated with
      conditioned medium from human mesangial cells in vitro. Levels of miR-223 in
      GEnCs decreased after incubation with the medium prepared with pIgA from patients
      with glomerular endothelial proliferation and were also decreased in the
      glomerular tissues of patients with glomerular endothelial proliferation.
      Mesangial-derived IL-6 caused miR-223 levels to decrease. The addition of
      exogenous miR-223 inhibited cell proliferation, ICAM-1 expression, and monocyte
      adhesion. The NF-kappaB and STAT3 signaling pathways collaborate during the
      activation process. MiR-223 mimics inhibited the nuclear localization and DNA
      binding of p65 and STAT3 but had no effect on the expression of upstream
      molecules. Instead, importin alpha4 and alpha5 (multipurpose nuclear transport
      receptors), validated as targets of miR-223, were responsible for the nuclear
      transport of p65 and STAT3. Importin alpha4 and alpha5 siRNA inhibited the
      nuclear localization of p65 and STAT3 and prevented cell proliferation and
      monocyte adhesion. The level of miR-223 in circulating endothelial cells was
      decreased and related to the clinical and pathological parameters. Thus, miR-223
      downregulation promotes glomerular endothelial cell activation by upregulating
      importin alpha4 and alpha5 in IgAN. Monitoring the level of miR-223 in
      circulating endothelial cells may provide a noninvasive method for evaluating the
      severity of IgAN. 

PMID- 24284510
TI  - Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.
AB  - Hydrogen sulfide has recently been found decreased in chronic kidney disease.
      Here we determined the effect and underlying mechanisms of hydrogen sulfide on a
      rat model of unilateral ureteral obstruction. Compared with normal rats,
      obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine
      beta-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in
      the ureteral obstructed kidney, but another enzyme cystathionine-gamma-lyase was
      increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal
      fibrosis by attenuating the production of collagen, extracellular matrix, and the
      expression of alpha-smooth muscle actin. Meanwhile, the infiltration of
      macrophages and the expression of inflammatory cytokines including interleukin
      1beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in the
      kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide
      donor inhibited the cell proliferation by reducing DNA synthesis and
      downregulating the expressions of proliferation-related proteins including
      proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor
      blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by
      inhibiting the transforming growth factor-beta1-Smad and mitogen-activated
      protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its
      releasing compounds may have therapeutic potentials in treating chronic kidney
      disease. 

PMID- 24284513
TI  - Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a
      framework for moving forward.
AB  - The 2012 KDIGO Guideline for CKD evaluation, classification, and management has
      updated the original 2002 KDOQI Guidelines, using newer data and addressing
      issues raised over the last decade concerning definitions and assessment. This
      review highlights the key aspects of the CKD guideline, and describes the
      rationale for specific wording and the scope of the document. A precis of key
      concepts in each of the five sections of the guideline is presented. The
      guideline document is intended for general practitioners and nephrologists, and
      covers CKD evaluation, classification, and management for both adults and
      children. Throughout the guideline, we have attempted to overtly address areas of
      controversy or non-consensus, international relevance, and impact on practice and
      public policy. 

PMID- 24284511
TI  - Periostin promotes renal cyst growth and interstitial fibrosis in polycystic
      kidney disease.
AB  - In renal cystic diseases, sustained enlargement of fluid-filled cysts is
      associated with severe interstitial fibrosis and progressive loss of functioning
      nephrons. Periostin, a matricellular protein, is highly overexpressed in cyst
      lining epithelial cells of autosomal-dominant polycystic disease kidneys (ADPKD)
      compared with normal tubule cells. Periostin accumulates in situ within the
      matrix subjacent to ADPKD cysts, binds to alphaVbeta3 and alphaVbeta5 integrins,
      and stimulates the integrin-linked kinase to promote cell proliferation. We
      knocked out periostin (Postn) in pcy/pcy mice, an orthologous model of
      nephronophthisis type 3, to determine whether periostin loss reduces PKD
      progression in a slowly progressive model of renal cystic disease. At 20 weeks of
      age, pcy/pcy:Postn(-/-) mice had a 34% reduction in kidney weight/body weight, a
      reduction in cyst number and total cystic area, a 69% reduction in phosphorylated
      S6, a downstream component of the mTOR pathway, and fewer proliferating cells in
      the kidneys compared with pcy/pcy:Postn(+/+) mice. The pcy/pcy Postin knockout
      mice also had less interstitial fibrosis with improved renal function at 20 weeks
      and significantly longer survival (51.4 compared with 38.0 weeks). Thus,
      periostin adversely modifies the progression of renal cystic disease by promoting
      cyst epithelial cell proliferation, cyst enlargement, and interstitial fibrosis,
      all contributing to the decline in renal function and premature death. 

PMID- 24284512
TI  - A multicolor podocyte reporter highlights heterogeneous podocyte changes in focal
      segmental glomerulosclerosis.
AB  - In contrast to most glomerular diseases, the injury pattern in focal segmental
      glomerulosclerosis (FSGS) is highly heterogeneous, even though podocytes are
      genetically identical and exposed to the same environmental factors. To
      understand changes in individual podocytes, we generated and analyzed a
      stochastic multicolor Cre-reporter, encoding four fluorescent proteins. In these
      animals, podocytes were randomly labeled allowing individual cells and their foot
      processes to be distinguished. In healthy animals, podocyte size and structure
      showed little cell to cell variability. In the doxorubicin-induced FSGS model,
      fluorescent-labeled glomerular podocyte numbers decreased and fluorescent cells
      could be recovered from the urine. The size of the remaining podocytes showed a
      high degree of heterogeneity, some cells remained small, while others enlarged.
      Both enlarged and non-enlarged podocytes showed alterations in their foot process
      morphology. Thus, by the virtue of a multicolor cre-reporter, individual
      podocytes could be viewed in real time at a cellular resolution indicating a
      heterogeneous podocyte injury response during the pathogenesis of FSGS. 

PMID- 24284514
TI  - Chronic kidney disease reduces muscle mitochondria and exercise endurance and its
      exacerbation by dietary protein through inactivation of pyruvate dehydrogenase.
AB  - Chronic kidney disease impairs physical performance. Here the time course and
      mechanism of muscle insufficiency in renal failure and the influence of dietary
      protein were studied using 5/6 nephrectomized C57Bl/6 mice, focusing on muscle
      mass and mitochondria. A decrease in muscle mitochondria and running distance was
      found in young (16-20 weeks) 5/6 nephrectomized mice, despite the preservation of
      muscle volume and power. However, a decrease in muscle volume, associated with a
      reduction in muscle power, was found in aged (48-52 weeks) 5/6 nephrectomized
      mice. A high-protein diet feeding from 8 weeks increased muscle volume and power
      in the mice; but this further decreased running distance. Activation of pyruvate
      dehydrogenase by dichloroacetate effectively recovered running distance that was
      decreased by dietary protein. These findings indicate the mechanism of muscle
      insufficiency in renal failure and suggest that activation of muscle mitochondria
      would serve as a potential strategy for improving the physical performance of the
      patients with chronic kidney disease. 

PMID- 24284515
TI  - A randomized controlled trial comparing intravesical to extravesical
      ureteroneocystostomy in living donor kidney transplantation recipients.
AB  - Urological complications after kidney transplantation are mostly related to the
      ureteroneocystostomy leading to significant morbidity, mortality, and high costs.
      The most commonly used techniques for the ureteroneocystostomy are the
      intravesical and the extravesical anastomosis. No evidence in favor of one of
      these two anastomoses exists. Our aim was to determine the technique with the
      best outcome regarding urological complications in a prospective randomized
      controlled trial (Netherlands Trial Register NTR2320). We randomized 200
      consecutive recipients of a living donor kidney for either an intravesical or an
      extravesical anastomosis. The primary outcome was defined as placement of a
      percutaneous nephrostomy. No significant differences were found in the number of
      percutaneous nephrostomy placements or ureter reinterventions between both
      groups. Nevertheless, significantly fewer urinary tract infections occurred in
      the group with an extravesical anastomosis. In addition, this anastomosis was
      performed significantly faster compared with the intravesical anastomosis. Thus,
      extravesical ureteroneocystostomy was associated with significantly fewer urinary
      tract infections and might be preferable because of its surgical simplicity. 

PMID- 24284516
TI  - Long-term risks for kidney donors.
AB  - Previous studies have suggested that living kidney donors maintain long-term
      renal function and experience no increase in cardiovascular or all-cause
      mortality. However, most analyses have included control groups less healthy than
      the living donor population and have had relatively short follow-up periods. Here
      we compared long-term renal function and cardiovascular and all-cause mortality
      in living kidney donors compared with a control group of individuals who would
      have been eligible for donation. All-cause mortality, cardiovascular mortality,
      and end-stage renal disease (ESRD) was identified in 1901 individuals who donated
      a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A
      control group of 32,621 potentially eligible kidney donors was selected, with a
      median follow-up of 24.9 years. Hazard ratio for all-cause death was
      significantly increased to 1.30 (95% confidence interval 1.11-1.52) for donors
      compared with controls. There was a significant corresponding increase in
      cardiovascular death to 1.40 (1.03-1.91), while the risk of ESRD was greatly and
      significantly increased to 11.38 (4.37-29.6). The overall incidence of ESRD among
      donors was 302 cases per million and might have been influenced by hereditary
      factors. Immunological renal disease was the cause of ESRD in the donors. Thus,
      kidney donors are at increased long-term risk for ESRD, cardiovascular, and all
      cause mortality compared with a control group of non-donors who would have been
      eligible for donation. 

PMID- 24284517
TI  - B cells display an abnormal distribution and an impaired suppressive function in
      patients with chronic antibody-mediated rejection.
AB  - In kidney transplantation, the composition of the B-cell compartment is
      increasingly identified as an important determinant for graft outcome. Whereas
      naive and transitional B cells have been associated with long-term allograft
      survival and operational tolerance, memory B cells have been linked to graft
      rejection and graft loss. Chronic antibody-mediated rejection now represents a
      major complication in transplantation and is a challenge in current therapeutics.
      Here, we show that patients with chronic antibody-mediated rejection display a
      unique B-cell phenotype with a reduced ratio of activated to memory B cells
      associated with an impaired immunosuppressive activity. The regulatory functions
      of the B cells depended on their maturation status. Thus, phenotypic and
      functional analyses of the B-cell compartment may be indicated for appropriate
      follow-up after transplantation and drive therapy in the establishment of
      transplant tolerance processes. 

PMID- 24284518
TI  - The reproducibility and predictive value on outcome of renal biopsies from
      expanded criteria donors.
AB  - Reproducibility and predictive value on outcome are the main criteria to evaluate
      the utility of histological scores. Here we analyze the reproducibility of donor
      biopsy assessment by different on-call pathologists and the retrospective
      evaluation by a single renal pathologist blinded to clinical outcomes. We also
      evaluate the predictive value on graft outcome of both evaluations. A biopsy was
      performed in donors with any of the following: age>=55 years, hypertension,
      diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial
      fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis
      evaluated according to the Banff criteria were added to obtain a chronic score.
      Biopsies were classified as mild (>=3), intermediate (4-5), or advanced (6-7)
      damage, and unacceptable (>=8) for transplantation of 127 kidneys biopsied.
      Weighted kappa value between both readings was 0.41 (95% CI: 0.28-0.54).
      Evaluation of biopsies by the renal pathologist was significantly and
      independently associated with estimated 12-month glomerular filtration rate and a
      significant composite outcome variable, including death-censored graft survival
      and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2.
      Thus, there was no association between readings of on-call pathologists and
      outcome. The lack of association between histological scores obtained by the on
      call pathologists and graft outcome suggests that a specific training on renal
      pathology is recommended to optimize the use of kidneys retrieved from expanded
      criteria donors.

PMID- 24284519
TI  - The high cost of organ transplant commercialism.
AB  - The Declaration of Istanbul defines organ transplant commercialism as '...a
      policy or practice in which an organ is treated as a commodity, including by
      being bought or sold or used for material gain.' It is this treatment of the
      organ that inevitably leads to its financial value being placed before the
      welfare of either its donor or its recipient or others in need of organ
      transplantation. International experience over the past two decades has proven
      this point and outcomes of commercial donation for both organ donors and their
      recipients have been poor. Commercial organ donation also comes at the expense
      of, not in addition to, unpaid, 'altruistic' donation. Other consequences of
      commercial donation are discussed in addition to a review of measures taken by
      the international community to put an end to the exploitation of vulnerable organ
      donors and the provision of ethically acceptable options for those in need of
      organ transplantation. 

PMID- 24284520
TI  - Podocyte injury enhances filtration of liver-derived angiotensinogen and renal
      angiotensin II generation.
AB  - Intrarenal angiotensin II is increased in kidney diseases independently of plasma
      angiotensin II and is thought to promote progressive deterioration of renal
      architecture. Here we investigated the mechanism of enhanced renal angiotensin II
      generation in kidney glomerular diseases. For this, kidney- or liver-specific
      angiotensinogen gene (Agt) knockout was superimposed on the mouse model of
      inducible podocyte injury (NEP25). Seven days after induction of podocyte injury,
      renal angiotensin II was increased ninefold in NEP25 mice with intact Agt,
      accompanied by increases in urinary albumin and angiotensinogen excretion, renal
      angiotensinogen protein, and its mRNA. Kidney Agt knockout attenuated renal Agt
      mRNA but not renal angiotensin II, renal, or urinary angiotensinogen protein. In
      contrast, liver Agt knockout markedly reduced renal angiotensin II to 18.7% of
      that of control NEP25 mice, renal and urinary angiotensinogen protein, but not
      renal Agt mRNA. Renal angiotensin II had no relationship with renal Agt mRNA, or
      with renal renin mRNA, which was elevated in liver Agt knockouts. Kidney and
      liver dual Agt knockout mice showed phenotypes comparable to those of liver Agt
      knockout mice. Thus, increased renal angiotensin II generation upon severe
      podocyte injury is attributed to increased filtered angiotensinogen of liver
      origin resulting from loss of macromolecular barrier function of the glomerular
      capillary wall that occurs upon severe podocyte injury. 

PMID- 24284521
TI  - Identification of breast cancer patients based on human signaling network motifs.
AB  - Identifying breast cancer patients is crucial to the clinical diagnosis and
      therapy for this disease. Conventional gene-based methods for breast cancer
      diagnosis ignore gene-gene interactions and thus may lead to loss of power. In
      this study, we proposed a novel method to select classification features, called
      "Selection of Significant Expression-Correlation Differential Motifs" (SSECDM).
      This method applied a network motif-based approach, combining a human signaling
      network and high-throughput gene expression data to distinguish breast cancer
      samples from normal samples. Our method has higher classification performance and
      better classification accuracy stability than the mutual information (MI) method
      or the individual gene sets method. It may become a useful tool for identifying
      and treating patients with breast cancer and other cancers, thus contributing to
      clinical diagnosis and therapy for these diseases. 

PMID- 24284522
TI  - Prevention of lipopolysaccharide-induced peritoneal damage by eplerenone in rats
      undergoing peritoneal dialysis.
AB  - BACKGROUND: Bacterial peritonitis in patients undergoing peritoneal dialysis (PD)
      is a major cause of therapy interruption due to peritoneal insufficiency. Here we
      studied the effect of a selective mineralocorticoid receptor (MR) blocker,
      eplerenone, on the prevention of peritoneal damage.? METHODS: Male Sprague-Dawley
      rats were treated with a daily infusion of human use PD solution (100 mL/kg i.p.,
      PD group, n = 5), or with PD solution and intermittent intraperitoneal injections
      of lipopolysaccharide (LPS group, n = 5) or with LPS and eplerenone (100
      mg/?kg/d, po, Ep group, n = 5) for 4 weeks. Peritoneal samples were subjected to
      assessment following the peritoneal equilibration test (PET). RESULTS:
      Histological observations revealed that LPS treatment resulted in significant
      peritoneal thickening associated with increased ED-1-positive cell infiltration
      and the number of transforming growth factor (TGF)-beta1-positive cells, and that
      eplerenone reduced these changes. LPS administration also evoked significant
      upregulation of monocyte chemotactic protein-1 and TGF-beta1, which were
      inhibited by eplerenone. PET revealed that ultrafiltration and transperitoneal
      osmotic diffusion were significantly impaired by LPS and restored by eplerenone.
      Increased value of the mass transfer area coefficients for creatinine values was
      also recovered by Ep (0.10 +/- ?0.01 in the PD, 0.14 +/- 0.02 in the LPS and 0.08
      +/- 0.0 in the Ep groups). Immunostaining for von Willebrand factor showed a
      significant increase by LPS and its restoration by Ep.? CONCLUSIONS: Ep
      effectively diminished LPS-induced peritoneal insufficiency. A selective blockade
      of MR might prevent peritoneal insufficiency associated with bacterial
      peritonitis.

PMID- 24284523
TI  - IgG4-related tubulointerstitial nephritis associated with chronic lymphocytic
      leukemia.
AB  - BACKGROUND: Tubulointerstitial nephritis (TIN) is typically seen in association
      with drug exposure and infection or in autoimmune diseases such as Sjogren's
      syndrome or systemic lupus erythematosis. The recently described IgG4-related
      systemic diseases can affect many organ systems including the kidney and
      typically respond to corticosteroid treatment. CASE: We present a case of IgG4
      related TIN in a patient with concomitant chronic lymphocytic leukemia. To our
      knowledge, IgG4-related TIN has not been associated with any hematological
      disorder such as chronic lymphocytic leukemia.? CONCLUSION: We propose that all
      kidney biopsies with significant plasma cell infiltrate should be stained for
      IgG4 as response to treatment is common.

PMID- 24284524
TI  - Current indications to parathyroidectomy in CKD patients before and after renal
      transplantation.
AB  - Secondary hyperparathyroidism (SHP) is one of the most challenging complications
      in the most advanced stages of end-stage renal disease. In the last decade, newly
      available medical tools have greatly increased the possibilities for controlling
      SHP. However, one of these tools, cinacalcet, has not yet been approved ?for its
      use in transplanted patients and the evidence for its safety in this clinical
      setting is still incomplete. For these reasons, many questions still remain open
      for the clinical nephrologist: when to consider a parathyroidectomy (PTX)  in a
      patient on a waiting list for kidney transplant  (KTx); when to recommend PTX
      after KTx; when could a regression of parathyroid hyperplasia ?be expected at any
      time after KTx. In the present paper, we will briefly deal with these questions
      in the light of an unusual clinical case. 

PMID- 24284525
TI  - Epidemiology and mortality among dialysis patients with parathyroidectomy: Taiwan
      ?National Cohort Study.
AB  - BACKGROUND AND OBJECTIVES: Parathyroidectomy (PTx) is usually necessary in
      patients with end-stage renal disease (ESRD) on dialysis. Risk factors for higher
      PTx rates are controversial. The objectives of this study were to identify the
      risk factors for PTx in patients on dialysis and evaluate the mortality after
      PTx. METHODS: We analyzed data obtained from the National Health Insurance
      Research Database and included 35,162 ESRD dialysis patients. Kaplan-Meier method
      was used to calculate the incidence of PTx and survival rate after PTx. Cox
      proportional hazards models were used to identify the risk factors. RESULTS: The
      PTx rate was 8.09 per 1,000 patient-years. Stratified on the basis of gender and
      diabetic mellitus (DM), the highest incidence rate of PTx was in females without
      DM. Stratified by age and DM, the highest incidence rate of PTx was in those aged
      18-44 years without DM. The significant risk factors for PTx were younger age,
      female (hazard ratio (HR) 1.409, 95% confidence interval (CI): 1.257-1.580), DM
      (HR 0.479, 95% CI: 0.413-0.555), peritoneal dialysis (HR 1.657, 95% CI: 1.418
      1.938) and hypertension (HTN) (HR 1.317, 95% CI: 1.162-1.492). The cumulative
      survival rates after PTx were 97.1%, 94.5%, 82.8% and 77.4% at the first, second,
      fifth and seventh year, respectively. Only age was significantly associated with
      higher mortality after PTx. CONCLUSIONS: Higher PTx rates were found in dialysis
      patients who were female and younger, did not have DM, were on peritoneal
      dialysis and had HTN. Advanced age was associated with a higher mortality after
      PTx.

PMID- 24284526
TI  - Glomerular filtration rate: utility for assessing long-term renal allograft
      outcomes in kidney allograft recipients.
AB  - Glomerular filtration rate (GFR) is the parameter currently used in renal
      transplantation to monitor renal function and to predict long-term survival of
      the graft. Due to practical difficulties in measuring GFR through inulin or
      creatinine clearance, formulas have been ?designed to estimate GFR from serum
      creatinine and indirect indices of creatinine production from muscles, i.e.,
      gender, age and body weight. These formulas have been used to monitor renal graft
      function and to predict graft outcome. Present evidence indicates that estimated
      GFR (eGFR) can be a relatively imprecise instrument to measure renal function,
      but remains useful for monitoring graft function and predicting graft outcome.
      Despite certain limitations, eGFR has provided invaluable information on the
      determinants of renal graft outcome, especially on the effects of different
      immunosuppressive regimens. A number of trials examining new immunosuppressive
      regimens (including calcineurin inhibitor minimization and novel therapeutics)
      have employed eGFR as an endpoint for assessing clinical benefit. In this
      capacity, eGFR ?assessment has provided important data for comparing regimens.
      This paper reviews the usefulness of eGFR for predicting renal transplant
      outcomes. 

PMID- 24284528
TI  - Headlines.

PMID- 24284527
TI  - Paraneoplastic minimal change nephropathy: a diagnostic challenge.
AB  - INTRODUCTION: Myeloma-associated glomerulopathy could mimic idiopathic minimal
      change nephropathy, which poses a diagnostic challenge to nephrologists. CASE
      REPORT: A 60-year-old patient presented with nephrotic range of proteinuria.
      Serum creatinine level was normal. Immune markers and tumor markers were
      unrevealing. No monoclonal protein was detected on serum protein electrophoresis.
      Renal biopsy showed marked effacement of foot processes and no evidence of
      immunoglobulin or amyloid deposition on electron microscopy/immunofluorescence
      staining, compatible with idiopathic minimal change nephropathy histologically.
      However, proteinuria persisted despite steroid treatment. In view of the atypical
      course of the disease, workup for secondary glomerulopathy was repeated and
      paraproteinuria was unexpectedly found. Subsequent bone marrow examination
      confirmed light chain myeloma. CONCLUSION: Urine protein electrophoresis and
      serum/urine immunofixation are useful tests to detect the monoclonal protein in
      suspicious cases.

PMID- 24284529
TI  - Presidential address of the American Orthopaedic Society for Sports Medicine:
      lifelong learning--mandate or mission?

PMID- 24284531
TI  - The tibial tubercle-trochlear groove distance on axial CT and MRI: letter to the
      editor.

PMID- 24284532
TI  - Radioisotope uptake on bone scintigraphy in rotator cuff patients: letter to the
      editor.

PMID- 24284533
TI  - National guidelines for the prevention and clinical management of dental trauma
      in individuals during their developmental age.

PMID- 24284534
TI  - Vancomycin resistant enterococci healthcare associated infections.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) are among the most common
      healthcare associated multidrug-resistant organisms. Purpose of the article was
      to review recent data regarding the epidemiology, clinical issues and infection
      control of this organisms. METHODS: A PubMed-MEDLINE search was carried out.
      RESULTS: The European Antimicrobial Resistance Surveillance System (EARSS)
      highlights a large variability between the various european countries, with VRE
      ranging from <2% (Finland, Holland) to >20% (Ireland, Greece, Portugal). Italy
      shows a low rate level (4.2%). In USA according to the National Healthcare Safety
      Network (NHSN) in 2006-2007 overall 33% of enterococci were resistant to
      vancomycin, whereas in Canada VRE prevalence showed to be much lower <10%.
      Although with some methodological limits, several studies showed that infections
      caused by VRE are more serious and associated to a higher mortality rate and
      economic burden compared to those caused by vancomycin susceptible enterococci
      (VSE). The average increased associated mortality was over two-fold. Resistance
      to newer antimicrobial agents as daptomycin and linezolid has been described,
      complicating treatment options for infections caused by these organisms.
      CONCLUSION: Control measures aimed at reducing the incidence of VRE colonization
      and infection in healthcare settings should include: hand washing with an
      antiseptic or a waterless antiseptic agent, routine screening for vancomycin
      resistance among clinical isolates, rectal surveillance cultures, contact
      isolation for patients with VRE and antimicrobial stewardship.

PMID- 24284535
TI  - The tubercular disease in immigrants without documents: new diagnostic settings
      adopted in Milan, Italy.
AB  - The tubercular disease (TB) is "the disease of poverty and people in need",
      spread in the poorest countries and among the less wealthy people of the western
      world (immigrants). In Italy the health authority has recently defined precise
      diagnostic and therapeutic patterns for TB. The social and health Association
      Naga in Milan with the Regional Reference Centre for TB, designed a screening
      system. In Naga's surgery all the undocumented immigrants, coming to Italy from
      countries with high TB incidence (> 100/100000) and high immigration rates, are
      screened by a questionnaire created by the Swiss Lung League; the suspect cases
      are sent to a designed centre for a second level of investigation. The use of
      this form allows to set a first selection based on the patients' anamnestic
      history, thus avoiding the intradermal reaction that, due to its low selectivity,
      could cause a 4 times higher crowding of the designed secondary centers.

PMID- 24284536
TI  - Alcohol consumption and awareness of the risks related in alcohol-abuse in high
      school students: evidence from a Health Education program.
AB  - BACKGROUND: The unceasing and widespread increase of alcohol consumption
      represents an important problem for the European Union. For this reason, we
      wanted to investigate the patterns of alcohol consumption among high-school
      students of Rieti, a city in central Italy, and of surrounding rural areas.
      Furthermore, the study intends to investigate students' awareness on alcohol
      related health risks and on the consequences of driving in a state of
      intoxication. METHODS: In the investigation 7 schools including senior high
      schools and technical schools were involved, for a total of 669 students aged
      between 15 and 19 years. As part of a program of health education, a self
      administered anonymous questionnaire was proposed to each student. A descriptive
      and multivariate analysis was carried out. RESULTS: The prevalence of usual
      drinkers was equal to 12.7 per cent. The logistic regression analysis showed a
      statistically significant association between usual consumption of alcohol and
      the attendance of Technical Institutes (OR=3.43; 95% IC: 2.07 - 5.69), and the
      residence in rural areas (OR=2.19; 95% IC: 1.38 - 3.47). The area of residence in
      the multivariate analysis loses significance. Only 54.6 % of the students
      answered the questions regarding the state of driving under the effect of
      alcohol; of these, 11.0 % declared of having driven at least once under the
      effect of alcohol, whereas 18.0 % declared that they had been passengers of a
      driver who was drunk. The answer to the question whether the consumption of
      alcohol is harmful to health was "no" for 15.7 % of usual drinkers against 2.2 %
      of the non drinkers or occasional (episodic) drinkers. CONCLUSIONS: Our study
      shows that the drinking habits of high school students of Rieti are worse for
      those attending technical schools. Usual drinkers show lower consciousness of
      alcohol-related harm. Our study may provide clues useful for the identification
      of the target population at high risk for alcohol abuse in order to create
      targeted prevention programs.

PMID- 24284537
TI  - Dynamic blood pressure in workers exposed to urban stressors.
AB  - BACKGROUND: The occupational exposure to urban pollution may induce adverse
      effects on the cardiovascular system. METHODS: Basal blood pressure,
      electrocardiogram (ECG) and the dynamic blood pressure monitoring during the work
      shift of 16 policemen (outdoors workers) and 16 administrative employees (indoor
      workers) were compared. RESULTS: The mean value of all the diastolic blood
      pressure surveys in policemen (84,53 +/- 10,78) is significantly higher (p =
      0,014) than the mean value of all the diastolic blood pressure surveys in indoor
      workers (82,74 +/- 11.52). CONCLUSIONS: The results of our study suggest that the
      occupational exposure to urban stressors may induce an increase of the diastolic
      blood pressure in workers during the working hours.

PMID- 24284539
TI  - Access to prenatal cytogenetic diagnosis in Catania: a retrospective survey.
AB  - BACKGROUND: To determine the incidence of chromosome abnormalities (CAs) in
      prenatal cytogenetic diagnosis, to describe and compare indications in Italian
      and migrant women, and to assess the level of compliance with published national
      guidelines. METHODS: A retrospective analysis of 7806 amniotic fluid samples
      (AFS) and 228 chorionic villi samples (CVS) was conducted. RESULTS: Advanced
      maternal age was the most common indication. CAs incidence was 3.1 per 100 AFS,
      and 12.6 per 100 CVS. Only parental chromosome rearrangement and ultrasound
      abnormalities were significantly associated with CA occurrence (RR= 20.15 95%CI:
      11.96-33.96; RR= 4.33; 95%CI: 2.95-6.36, respectively). Both in amniocentesis and
      in chorionic villi sampling CA incidence was significantly higher when performed
      according to the national guidelines, than for other reasons. Incidence data for
      trisomy 21, trisomy 18 and inversions were significantly higher than those
      reported in a previous Italian report. CONCLUSIONS: Increased maternal age may
      explain, at least in part, the increase by time of CAs, although an excess was
      shown in our population independently from it. Our results show that advanced
      maternal age may not be sufficient as a single criterion for prenatal diagnosis,
      and suggesting a future revision of national clinical indications is suggested.

PMID- 24284538
TI  - Liver function in workers exposed of the cosmetics industry.
AB  - BACKGROUND: The purpose of this study is to assess whether occupational exposure
      to substances used in the cosmetic factories may cause effects on the liver and
      blood counts in exposed workers. METHODS: The study included 48 exposed workers
      and 86 unexposed controls. All workers included in the study underwent blood
      count, white blood count, total, direct and indirect bilirubin, transaminases,
      alkaline phosphatase and cholinesterase. The differences between the means and
      frequencies were compared using the Student's t-test and chi-square test with
      Yates correction and were considered significant when the p value was <0.05.
      RESULTS: The analysis of the results shows that 35.4% of workers in the cosmetics
      industry had liver test values above the range. We noted a statistically
      significant higher prevalence of GPT (p <0.05) and total bilirubin (p <0.05) in
      the workers of the cosmetics industry compared with the control group.
      CONCLUSIONS: The results obtained suggest that occupational exposure to low doses
      of substances used in the cosmetic industry is able to influence some liver
      parameters in occupationally exposed workers.

PMID- 24284540
TI  - Request for ethics support in healthcare practices. Reasons and characteristics
      of Ethics Consultation Service users.
AB  - BACKGROUND: Ethical problems in healthcare practices are increasing. Therefore,
      healthcare professionals encounter difficult ethical problems more frequently in
      their professional activities. For this reason, in several countries Ethics
      Consultation Services have been created, and a debate concerning their role and
      organization model has developed. Despite the great interest of healthcare
      professionals in ethics support, Ethics Consultation Services are scarcely
      diffused in Italy. METHODS: A survey was conducted to identify the levels of the
      nurses' experience and knowledge in the field of ethics and to assess their
      willingness to use a consultation service to approach ethical issues in
      healthcare. A questionnaire was administered and completed personally by 374
      nurses appropriately instructed beforehand on its use. They were recruited from
      post-basic training courses at the Faculty of Medicine and Surgery of the
      University of L'Aquila. RESULTS: The willingness to recur to an ethical
      consultation, indicated by 90.3% of respondents, would confirm the hypothesis
      that the increasing ethical difficulties encountered in healthcare activities
      determined a greater interest towards this kind of service. The results of the
      study underline both the need and expectations the nurses have for ethics
      consultation and support to face ethical difficulties in patient care, and
      describe the characteristics of potential users. CONCLUSION: In our country the
      delay in approaching such problems is in contrast with the marked interest the
      healthcare professionals have for a possible request for support to face ethical
      problems in patient care. The study shows the respondents' high degree of
      appreciation of the contents of an ethics consultation activity and,
      consequently, it is desirable that the creation of an Ethics Consultation Service
      takes into consideration the indications given by the potential users, in
      addition to the experiences coming from other countries.

PMID- 24284541
TI  - Inadequate antibiotic therapy of genitourinary tract infections could be
      responsible for viral sexually transmitted diseases.

PMID- 24284542
TI  - Antibiotic effects on vaginal microbiota.

PMID- 24284543
TI  - Ultrasonic biodiesel synthesis from crude Jatropha curcas oil with heterogeneous
      base catalyst: mechanistic insight and statistical optimization.
AB  - This paper reports studies in ultrasound-assisted heterogeneous solid catalyzed
      (CaO) synthesis of biodiesel from crude Jatropha curcas oil. The synthesis has
      been carried out in two stages, viz. esterification and trans-esterification. The
      esterification process is not influenced by ultrasound. The transesterification
      process, however, shows marked enhancement with ultrasound. A statistical
      experimental design has been used to optimize the process conditions for the
      synthesis. XRD analysis confirms formation of Ca(OMe)2, which is the active
      catalyst for transesterification reaction. The optimum values of parameters for
      the highest yield of transesterification have been determined as follows: alcohol
      to oil molar ratio ~ 11, catalyst concentration ~ 5.5 wt.%, and temperature ~ 64
      degrees C. The activation energy of the reaction is calculated as 133.5 kJ/mol.
      The heterogeneity of the system increases mass transfer constraints resulting in
      approx. 4 * increase in activation energy as compared to homogeneous alkali
      catalyzed system. It is also revealed that intense micro-convection induced by
      ultrasound enhances the mass transfer characteristics of the system with ~ 20%
      reduction in activation energy, as compared to mechanically agitated systems.
      Influence of catalyst concentration and alcohol to oil molar ratio on the
      transesterification yield is inter-linked through formation of methoxy ions and
      their diffusion to the oil-alcohol interface, which in turn is determined by the
      volume fractions of the two phases in the reaction mixture. As a result, the
      highest transesterification yield is obtained at the moderate values of catalyst
      concentration and alcohol to oil molar ratio.

PMID- 24284544
TI  - Common and distinct structural features of Salmonella injectisome and flagellar
      basal body.
AB  - Bacterial pathogens use an injectisome to deliver virulence proteins into
      eukaryotic host cells. The bacterial flagellum and injectisome export their
      component proteins for self-assembly. These two systems show high structural
      similarities and are classified as the type III secretion system, but it remains
      elusive how similar they are in situ because the structures of these complexes
      isolated from cells and visualized by electron cryomicroscopy have shown only the
      export channel and housing for the export apparatus. Here we report in situ
      structures of Salmonella injectisome and flagellum by electron cryotomography.
      The injectisome lacks the flagellar basal body C-ring, but a wing-like disc and a
      globular density corresponding to the export gate platform and ATPase hexamer
      ring, respectively, are stably attached through thin connectors, revealing yet
      unidentified common architectures of the two systems. The ATPase ring is far from
      the disc, suggesting that both apparatuses are observed in an export-off state. 

PMID- 24284545
TI  - Hospital-based health technology assessment on the use of mitral clips in the
      treatment of mitral regurgitation.
AB  - BACKGROUND: This study, carried out at the Florence Teaching Hospital Careggi
      (AOUC), reports the technological evaluation, through the use of Health
      Technology Assessment (HTA), on the application of mitral clips in the treatment
      of mitral insufficiency. OBJECTIVE: The assessment, carried out by analyzing the
      clinical, technological, social, procedural, safety and economic elements, sought
      to answer the following research questions: Evaluation of the general
      technological status of the mitral clips in the treatment process of mitral
      regurgitation, with particular reference to traditional methods; and
      contextualisation of the analyses within the hospital structure, by identifying
      criticality issues and improvements. METHODS: The methodology was based on the
      following steps: technological description; areas of evaluation and the selection
      of Key Performance Indicators; research of scientific facts and the collection of
      expert opinions; evaluation and reporting of findings. RESULTS: The results are
      based on an analysis which included a total of 50 indicators, effectively
      evaluating 86.5% of them, from the least from the clinical sector (80%) to the
      most in the areas of procedure, safety and social (100%). Traditional surgery
      (repair or valve replacement) still represents the gold standard for the
      treatment of mitral regurgitation due to its maturity both on a technological and
      clinical level. The minimally invasive procedures which use the mitral clips
      present interesting opportunities both on a social level (minimum stay in
      hospital and no post-operative rehabilitation) and clinical level, especially as
      an alternative to medication, even if they are still at an emergent level (the
      long-term results are unknown) and complex to use. From the clinical point of
      view they show some interesting findings related to immediate and post-operative
      mortality (none during the operation and a minor and equal amount 30 days and 12
      months later in comparison to traditional methods) whilst economically, despite
      the fact that the cost of the device is greater than those used in traditional
      interventions, the cost-refund relationship does not show significant differences
      compared to the traditional types of treatment. CONCLUSION: The HTA evaluation of
      minimally invasive technologies that use clips for the treatment of mitral
      regurgitation shows, in the hospital setting, very interesting results,
      particularly for inoperable patients, where the clinical and social improvements
      are significant compared to pharmacological treatments, whilst for 'operable'
      patients, the traditional techniques are still the most appropriate.

PMID- 24284546
TI  - Development of digitized apparatus for upper limb rehabilitation training.
AB  - BACKGROUND: People use upper limbs to conduct daily activities. When recovering
      from injuries, many patients neglect the importance of rehabilitation, which
      results in degraded function. OBJECTIVE: Rehabilitation after treatment of an
      injury is very important. This study proposes to improve and enhance the
      effectiveness of rehabilitation practice. METHODS: A patient record of the
      training process using the traditional rehabilitation hand gliding cart is
      produced by using a magnetic sensing element in the panel, a servo host computer,
      and other devices. RESULTS: Clinical evidence shows that the training aids help
      significantly with the rehabilitation of patients with impaired upper limb
      function and reduce negative impacts from the disability in daily life and
      activities. CONCLUSIONS: This study has combined the gliding cart with reed
      switches, such that when the patient moves the cart, the movement tracks can be
      observed via the activated reed switches. The training data are collected and
      quantified for a better understanding of the recovery status of the patients.
      Each of the participating patients makes progress as expected.

PMID- 24284547
TI  - The interactive animated epilepsy education programme (IAEEP): how feasible,
      acceptable and practical is the technology to children?
AB  - BACKGROUND: Being well-informed and knowledgeable about their illnesses would be
      a great advantage to children with epilepsy (CWE). Subsequently, an effective
      education programme which could secure interest and simultaneously improve their
      awareness, knowledge and attitudes (AKA) is essential in enhancing well-being and
      health outcomes. OBJECTIVES: To describe the development of a new interactive
      animated epilepsy education programme (IAEEP) for children and to assess its
      feasibility, acceptability and practicality. METHODS: The IAEEP was developed by
      an interdisciplinary group of neurologist, paediatrician, pharmacist, biomedical
      scientist and educators which was based on two established epilepsy education
      programmes: the educational programme for patients with epilepsy and their
      relatives (MOSES) and the modular educational program for children with epilepsy
      and their parents (FAMOSES). CWE from paediatric department of three general
      hospitals in Terengganu were initially introduced to the IAEEP and were requested
      to complete an evaluation form assessing its feasibility, acceptability and
      practicality. Descriptive statistics were employed for data analyses (SPSS 20.0).
      RESULTS: Sixteen CWE (median age=13.0; male=56.2%; Malay=81.2%; secondary
      school=56.2%) and their corresponding parents were recruited. Each CWE owned at
      least a computer/notebook/tablet (100%). The cost of distribution of IAEEP (in
      compact disc form) among CWE was estimated at about MYR 17.99/USD 5.90 per CWE.
      The average time required to interact with the programme was 22.8 minutes
      (SD=3.3, range 18-28 minutes). The programme was 100% acceptable and received
      full support from both CWE and their parents (100%). CONCLUSIONS: The favourable
      findings from this study add to the growing evidence suggesting that investment
      in interactive and animated education programme would be both feasible, well
      received by patients and could be a potentially valuable approach to increase
      access and effectiveness of epilepsy care especially among CWE.

PMID- 24284548
TI  - The role of arthroscopy in patients with persistent hip pain after total hip
      arthroplasty.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a safe and successful procedure for
      the treatment of osteoarthritis. One of the most common postoperative problems
      remains persistent hip pain. The arthroscopic evaluation of persistent hip pain
      following THA can be a valuable diagnostic tool in a select number of patients
      when carried out by experts in this technique. OBJECTIVE: Indication for
      arthroscopy was persistent pain after THA. Inclusion criteria were an absence of
      radiological loosening and a sterile aspiration 6 weeks before arthroscopy. Hip
      joint function and pain were evaluated pre- and postoperatively using the visual
      analogue scale (VAS) and the Hip Outcome Score (HOS), which scored the activities
      of daily living (ADL), and a sports subscale. METHODS: 5 patients (3 female, 2
      male) with an average age of 60.2 +/- 4.27 years (range 51-72 years) were
      included in the study. Arthroscopy with biopsy, adhesiolysis and psoas tendon
      release was performed 21.0 +/- 21.97 months (range 6-57 months) after primary hip
      replacement. RESULTS: Pathological findings were prosthetic joint infection (two
      cases), impingement between acetabular component and psoas tendon (two cases),
      adhesions of the periprosthetic tissue (one case). The patients achieved a
      significant improvement of the Hip Outcome Score (HOS), from an average of 45.6
      +/- 22.5 (range 14.0-63.1) to 76.5 +/- 3.8 (range 41.0-89.4, P=0.016). Evaluation
      of the VAS showed a significant improvement from a preoperative value of 8.8 +/-
      0.5 to a postoperative value of 3.4 +/- 1.0 (P=0.001). CONCLUSION: Hip
      arthroscopy provides a minimal-invasive tool for diagnosis and therapy. In cases
      of persistent pain after THA, standard diagnostic procedures should be utilised.
      Arthroscopy of a hip post-THA would be highly specialised. As a next step,
      arthroscopy helps the diagnosis and therapy of persistent pain after THA.

PMID- 24284549
TI  - An automated retinal imaging method for the early diagnosis of diabetic
      retinopathy.
AB  - BACKGROUND: Diabetic retinopathy is a microvascular complication of long-term
      diabetes and is the major cause for eyesight loss due to changes in blood vessels
      of the retina. Major vision loss due to diabetic retinopathy is highly
      preventable with regular screening and timely intervention at the earlier stages.
      Retinal blood vessel segmentation methods help to identify the successive stages
      of such sight threatening diseases like diabetes. OBJECTIVE: To develop and test
      a novel retinal imaging method which segments the blood vessels automatically
      from retinal images, which helps the ophthalmologists in the diagnosis and follow
      up of diabetic retinopathy. METHODS: This method segments each image pixel as
      vessel or nonvessel, which in turn, used for automatic recognition of the
      vasculature in retinal images. Retinal blood vessels were identified by means of
      a multilayer perceptron neural network, for which the inputs were derived from
      the Gabor and moment invariants-based features. Back propagation algorithm, which
      provides an efficient technique to change the weights in a feed forward network,
      is utilized in our method. RESULTS: Quantitative results of sensitivity,
      specificity and predictive values were obtained in our method and the measured
      accuracy of our segmentation algorithm was 95.3%, which is better than that
      presented by state-of-the-art approaches. CONCLUSIONS: The evaluation procedure
      used and the demonstrated effectiveness of our automated retinal imaging method
      proves itself as the most powerful tool to diagnose diabetic retinopathy in the
      earlier stages.

PMID- 24284550
TI  - Navigated reconstruction of tibial head depression fractures by inflation
      osteoplasty.
AB  - BACKGROUND: Articular fracture reduction control remains a challenge even with
      the development of computer-assisted surgery. The Kyphoplasty procedure has shown
      advantages in treating vertebral fractures. One case report showed successful
      reduction of acetabular fractures using Kyphoplasty. OBJECTIVE: This study
      examines the efficacy of this method in reducing depressed tibial plateau
      fractures. METHODS: An insertion sleeve for the Kyphon balloon that could be
      calibrated by the navigation system was designed. A total of 30 test series in
      synthetic bone cubes were performed using fracture instruments of 2.5 mm, 5 mm
      and 15 mm diameter, respectively, creating three different depression fracture
      depths (mean 1.87 mm, 4.2 mm and 1.72 mm, respectively). The Kyphon balloon was
      used to attempt reduction of each fracture. The same setup was used for testing
      in five cadaveric tibia specimens. RESULTS: After reduction, there was a
      remaining depression depth mean in the synthetic bone of 0.27 mm for the 2.5 mm
      instrument; 2.1 mm for the 5 mm instrument; and 1.72 mm for the 15 mm instrument.
      We could not adequately reduce depression fractures in cadaveric testing.
      CONCLUSIONS: The Kyphon balloon was accurately placed with the aid of navigation.
      The depth was the decisive factor in the reduction of the fracture and not the
      diameter. In cadavers, depression fractures greater than 5~mm depth could not be
      reduced with our setup.

PMID- 24284551
TI  - A pilot study to assess perceptions of using SMS as a medium for health
      information in a rural setting.
AB  - BACKGROUND: Information and Communication Technologies (ICTs) in health is not
      merely about technology but a means to reach various optimal outcomes across the
      entire health system. OBJECTIVE: The objective of this pilot study is to assess
      the perceptions of receiving health messages through SMS among individuals living
      in rural Indian settings. METHODS: A convenient sample of 100 individuals aged 18
      years and above and living in rural settings of Kuthampakkam village in Chennai,
      a Southern part of India were enrolled during September 2013. Individuals having
      the mobile phone and agreeing to participate were enrolled in the study.
      Individuals with physical and mental challenges or involved in other clinical
      trials were excluded from the study. Information was gathered on the variables
      including socio-demographics, individual familiarity with use of technology,
      mobile phone usage and the perceptions of using SMS for obtaining health
      information. Information was gathered using a series of quantitative assessments.
      Descriptive analysis was performed to report means and standard deviations for
      the continuous variables and frequency analysis was reported for the categorical
      variables. Analysis of variance (ANOVA) was used to compare the means of the
      various continuous variables as compared to the chi-square analysis that was
      performed to compare the frequency distribution for the categorical variables.
      All analysis was performed using SAS v9.1. RESULTS: A convenient sample of 100
      rural individuals was enrolled. The average age of the study participants was 34
      years (SD=17), with more than half of them being males (54%; n=54), and 47%
      (n=47) of them had education less than high school. Results showed that more than
      half of the individuals had no computers either at home (61%; n=61) or work (68%;
      n=68). 100{?%} of them had mobile phones in their household. Text messaging was
      common in more than half of the study participants. Results showed that the
      majority of the study participants agreed that receiving calls on the mobile
      phones for receiving health messages would be the most preferred method. Results
      showed that the individuals in the age group of 21-40 years, males, with some
      college education, and in the income category of 50,000-1,00,000 were most likely
      to obtain SMS based health messages. CONCLUSIONS: ICT based health programs need
      to be established so that the audience receives the optimal technological
      platform program necessary to obtain health messages. This also suggests that
      future research is needed to determine the population that would actually adopt
      the use of SMS based health interventions rather than using SMS as a tool for
      delivery of health information to all.

PMID- 24284552
TI  - Evaluation of upper extremity reachable workspace using Kinect camera.
AB  - BACKGROUND: In clinical evaluation of upper extremity, there is a lack of
      assessment methods that are quantitative, reliable, and informative of the
      overall functional capability of an individual. OBJECTIVE: We present new
      methodology for the assessment of upper extremity impairments based on the
      concept of 3-dimensional reachable workspace using Microsoft Kinect. METHODS: We
      quantify the reachable workspace by the relative surface area representing the
      portion of the unit hemi-sphere that is covered by the hand movement. We examine
      accuracy of joint positions, joint angles, and reachable workspace computation
      between the Kinect and motion capture system. RESULTS: The results of our
      analysis in 10 healthy subjects showed that the accuracy of the joint positions
      was within 66.3 mm for our experimental protocol. We found that the dynamic angle
      measurements had relatively large deviations (between 9 degrees  to 28 degrees ).
      The acquired reachable workspace envelope showed high agreement between the two
      systems with high repeatability between trials (correlation coefficients between
      0.86 and 0.93). CONCLUSIONS: The findings indicate that the proposed Kinect-based
      3D reachable workspace analysis provides sufficiently accurate and reliable
      results as compared to motion capture system. The proposed method could be
      promising for clinical evaluation of upper extremity in neurological or
      musculoskeletal conditions.

PMID- 24284553
TI  - A turn-on highly selective and ultrasensitive determination of copper (II) in an
      aqueous medium using folic acid capped gold nanoparticles as the probe.
AB  - This paper describes a 'turn-on' fluorescent determination of Cu(II) in an
      aqueous medium using folic acid capped gold nanoparticles (FA-AuNPs) as the
      probe. The FA-AuNPs were synthesized by the wet chemical method and were
      characterized by UV-visible, fluorescence, HR-TEM, XRD, zeta potential, and DLS
      techniques. The FA-AuNPs show an absorption maximum at 510 nm and an emission
      maximum at 780 nm (lambda(ex): 510 nm). On adding 10 MUM Cu(II), the wine-red
      color of FA-AuNPs changed to purple and the absorbance at 510 nm decreased. The
      observed changes were ascribed to the aggregation of AuNPs. This was confirmed by
      DLS and HR-TEM studies. Interestingly, the emission intensity of FA-AuNPs was
      enhanced even in the presence of a picomolar concentration of Cu(II). Based on
      the enhancement of the emission intensity, the concentration of Cu(II) was
      determined. The FA-AuNPs showed an extreme selectivity towards the determination
      of 10 nM Cu(II) in the presence of 10,000-fold higher concentration of
      interferences except EDTA and the carboxylate anion. A good linearity was
      observed from 10 * 10(-9) to 1 * 10(-12) M Cu(II), and the detection limit was
      found to be 50 fM l(-1) (S/N = 3). The proposed method was successfully applied
      to determine Cu(II) in real samples. The results obtained were validated with ICP
      AES.

PMID- 24284554
TI  - Foster Kennedy syndrome: now and then.

PMID- 24284555
TI  - Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene:
      report of a novel mutation and review of the literature.
AB  - Combined oxidative phosphorylation deficiency type 7 (COXPD7) is a rare disorder
      of mitochondrial metabolism that results in optic atrophy and Leigh syndrome-like
      disease. We describe 2 siblings with compound heterozygous mutations in the
      recently identified C12orf65 gene who presented with optic atrophy and mild
      developmental delays and subsequently developed bilateral, symmetric lesions in
      the brainstem reminiscent of Leigh syndrome. Repeat neuroimaging demonstrated
      reversibility of the findings in 1 sibling and persistent metabolic stroke in the
      other. This article highlights the phenotypic manifestations from a novel
      mutation in the C12orf65 gene and reviews the clinical presentation of the 5
      other individuals reported to date who carry mutations in this gene.

PMID- 24284556
TI  - Pulmonary air crescent sign.

PMID- 24284557
TI  - Rate-limiting step analysis of the microbial desulfurization of dibenzothiophene
      in a model oil system.
AB  - A mechanistic analysis of the various mass transport and kinetic steps in the
      microbial desulfurization of dibenzothiophene (DBT) by Rhodococcus erythropolis
      IGTS8 in a model biphasic (oil-water), small-scale system was performed. The
      biocatalyst was distributed into three populations, free cells in the aqueous
      phase, cell aggregates and oil-adhered cells, and the fraction of cells in each
      population was measured. The power input per volume (P/V) and the impeller tip
      speed (vtip ) were identified as key operating parameters in determining whether
      the system is mass transport controlled or kinetically controlled. Oil-water DBT
      mass transport was found to not be limiting under the conditions tested.
      Experimental results at both the 100 mL and 4 L (bioreactor) scales suggest that
      agitation leading to P/V greater than 10,000 W/ m(3) and/or vtip greater than
      0.67 m/s is sufficient to overcome the major mass transport limitation in the
      system, which was the diffusion of DBT within the biocatalyst aggregates.

PMID- 24284558
TI  - Antimicrobial activity of poultry bone and meat trimmings hydrolyzates in low
      sodium turkey food.
AB  - This research was aimed at the evaluation of the antimicrobial activity exerted
      by poultry protein hydrolyzates derived from industrial leftovers added to minced
      turkey meat, intended for the production of burgers for human consumption.
      Hydrolyzates were obtained through enzymatic hydrolysis from poultry bone and
      meat trimmings, as by-products from the poultry industry. Colony forming unit
      assays, under both laboratory and industrial conditions, were performed to assess
      microbial growth. Poultry protein hydrolyzates inhibited microbial growth
      occurring in semi-finished turkey meat during the normal retention period because
      of their water holding capacity resulting in a decreased water activity. Overall,
      the findings demonstrated that poultry protein hydrolyzates could decrease
      mesophilic, psychrophilic, and thermophilic bacterial growth for the entire
      product shelf-life. Bacterial growth inhibition obtained in minced turkey meat by
      addition of poultry protein hydrolyzates (1.5%), hygroscopic amino acids mixture
      (1.5%) or sodium chloride (1%) was similar. It is suggested that the use of
      hydrolyzates could allow the reduction of salt content in poultry meat based
      products leading to the production of low-sodium turkey food still maintaining
      acceptable sensory characteristics. 

PMID- 24284559
TI  - Differences in group size and the extent of individual participation in group
      hunting may contribute to differential prey-size use among social spiders.
AB  - We have previously shown that the range of prey sizes captured by co-occurring
      species of group-hunting social spiders correlates positively with their level of
      sociality. Here, we show that this pattern is probably caused by differences
      among species in colony size and the extent to which individuals participate in
      group hunting. We assess levels of participation for each species from the
      fraction of individuals responding to the struggling prey that partake as
      attackers and from the extent to which the number of attackers increases with
      colony size. Of two species that form equally large colonies, the one that
      captures on average larger prey engaged as attackers a significantly larger
      fraction of individuals that responded to struggling prey and also increased its
      number of attackers in larger colonies when presented with large prey items.
      Surprisingly, a third co-occurring species previously found to capture smaller
      insects than the other two exhibited the highest levels of participation. This
      species, however, typically forms small single-family colonies, thereby being
      limited in the size of insects it can capture. It is thus a combination of colony
      size and the extent of individual participation (or cooperation) that probably
      determines patterns of resource use in this community of co-occurring social
      predators. 

PMID- 24284560
TI  - Fatal attraction: sexually cannibalistic invaders attract naive native mantids.
AB  - Overlap in the form of sexual signals such as pheromones raises the possibility
      of reproductive interference by invasive species on similar, yet naive native
      species. Here, we test the potential for reproductive interference through
      heterospecific mate attraction and subsequent predation of males by females of a
      sexually cannibalistic invasive praying mantis. Miomantis caffra is invasive in
      New Zealand, where it is widely considered to be displacing the only native
      mantis species, Orthodera novaezealandiae, and yet mechanisms behind this
      displacement are unknown. We demonstrate that native males are more attracted to
      the chemical cues of introduced females than those of conspecific females.
      Heterospecific pairings also resulted in a high degree of mortality for native
      males. This provides evidence for a mechanism behind displacement that has until
      now been undetected and highlights the potential for reproductive interference to
      greatly influence the impact of an invasive species. 

PMID- 24284561
TI  - A simple explanation for the evolution of complex song syntax in Bengalese
      finches.
AB  - The songs of Bengalese finches (Lonchura striata var. domestica) have complex
      syntax and provide an opportunity to investigate how complex sequential behaviour
      emerges via the evolutionary process. In this study, we suggest that a simple
      mechanism, i.e. many-to-one mapping from internal states onto syllables, may
      underlie the emergence of apparent complex syllable sequences that have higher
      order history dependencies. We analysed the songs of Bengalese finches and of
      their wild ancestor, the white-rumped munia (L. striata), whose songs are more
      stereotypical and simpler compared with those of Bengalese finches. The many-to
      one mapping mechanism sufficiently accounted for the differences in the
      complexity of song syllable sequences of these two strains. 

PMID- 24284562
TI  - A century-long genetic record reveals that protist effective population sizes are
      comparable to those of macroscopic species.
AB  - Effective population size (Ne) determines the rate of genetic drift and the
      relative influence of selection over random genetic changes. While free-living
      protist populations characteristically consist of huge numbers of cells (N), the
      absence of any estimates of contemporary Ne raises the question whether protist
      effective population sizes are comparably large. Using microsatellite genotype
      data of strains derived from revived cysts of the marine dinoflagellate
      Pentapharsodinium dalei from sections of a sediment record that spanned some 100
      years, we present the first estimates of contemporary Ne for a local population
      in a free-living protist. The estimates of Ne are relatively small, of the order
      of a few 100 individuals, and thus are similar in magnitude to values of Ne
      reported for multicellular animals: the implications are that Ne of P. dalei is
      of many orders of magnitude lower than the number of cells present (Ne/N ~ 10(
      12)) and that stochastic genetic processes may be more prevalent in protist
      populations than previously anticipated. 

PMID- 24284563
TI  - ISPRM discussion paper: Proposing a conceptual description of health-related
      rehabilitation services.
AB  - There is a need for a comprehensive classification system of health-related
      rehabilitation services. For conceptual clarity our aim is to provide a health
      related conceptual description of the term "rehabilitation service". First, we
      introduce a common understanding of the term "rehabilitation", based on the
      current definition in the World Health Organization's World Report on Disability,
      and a conceptual description of rehabilitation agreed upon by international
      Physical and Rehabilitation Medicine organizations. From a health perspective,
      rehabilitation can be regarded as a general health strategy with the aim of
      enabling persons with health conditions experiencing or likely to experience
      disability to achieve and maintain optimal functioning. Secondly, we distinguish
      different meanings of the term "service", that have originated in management
      literature. It is important to distinguish between micro, meso and macro level
      uses of the term "service". On a meso level, which is central for the
      classification of rehabilitation services, 2 aspects of a service, i.e. an offer
      of an intangible product and an organizational setting in which the offer is
      upheld, are both essential. The results of this conceptual analysis are used to
      develop a conceptual description of health-related rehabilitation, which is set
      out at the end of this paper. This conceptual description may provide the basis
      of a classification of health-related rehabilitation services, and is open for
      comments and discussion. 

PMID- 24284564
TI  - Schwann cells differentiated from adipose-derived stem cells for the treatment of
      brain contusion.
AB  - Rapid development of tissue engineering techniques has led to the possibility of
      treating central nervous injuries with Schwann cells (SCs). However, certain
      characteristics of SCs, such as a low proliferation ability, greatly restrict
      their use. The aim of the present study was to investigate whether SCs
      differentiated from adipose-derived stem cells (ADSC-SCs) could used to promote
      functional recovery in brain contusion in rat. ADSCs were isolated and expanded
      from the groin of Sprague-Dawley rats and differentiated into SCs. The ADSC-SCs
      were transplanted into the contused rat brain and the locomotor function of the
      rats was assessed. Significant locomotor function recovery was observed in
      hemiparalyzed rats treated with ADSCs-SCs. In conclusion, transplantation of ADSC
      SCs significantly promoted functional recovery following brain contusion.

PMID- 24284565
TI  - Straight talk about nursing.

PMID- 24284566
TI  - For Mom and Malala.

PMID- 24284567
TI  - Positive deviance.

PMID- 24284568
TI  - Positive deviance.

PMID- 24284569
TI  - Patient agitation.

PMID- 24284572
TI  - The global status of women's health.

PMID- 24284573
TI  - Most breast cancer deaths occur in unscreened women.

PMID- 24284575
TI  - Disaster-response nursing.

PMID- 24284578
TI  - The new health insurance marketplace.

PMID- 24284585
TI  - Quiet at night: implementing a nightingale principle.

PMID- 24284586
TI  - Toleration of noises. 1914.

PMID- 24284587
TI  - Family pet visitation.

PMID- 24284588
TI  - One Health at Kansas State University.

PMID- 24284595
TI  - The brat.

PMID- 24284596
TI  - A mind in search of its moorings.

PMID- 24284597
TI  - Hiding a tender soul.

PMID- 24284598
TI  - Increased myofiber remodelling and NFATc1-myonuclear translocation in rat
      postural skeletal muscle after experimental vestibular deafferentation.
AB  - BACKGROUND: The vestibular system undergoes considerable modification during
      spaceflight [5]. This is paralleled by microgravity-induced muscle atrophy [6].
      However, the possibility of vestibulo-autonomic regulatory mechanisms affecting
      skeletal muscle structure and function have not yet been addressed. OBJECTIVE: We
      hypothesise that the vestibular system affects anti-gravitational skeletal muscle
      phenotype composition, size and the transcriptional factor called nuclear factor
      of activated T cells (NFATc1). METHODS: In a laboratory study, we examined the
      morphological and histochemical properties including intramyocellular NFATc1
      changes in slow-type soleus muscle of chemically labyrinthectomized rats (VLx;
      n=8) compared to a control group (Sham; n=6) after a period of one month. RESULTS
      AND CONCLUSION: Neurochemical vestibular deafferentation resulted in smaller
      myofibre sizes, altered myofibre phenotype composition, high yields of hybrid
      fibre formation, and reduced myonuclear NFATc1 accumulation as signs of slow-type
      myofibre atrophy, myofibre type remodelling, and altered nuclear transcriptional
      activity in the postural soleus muscle of rats. We propose that vestibulo
      autonomic modification of skeletal muscles occurs during prolonged microgravity.
      Our findings are likely to have implications for vestibular rehabilitation in
      clinical settings.

PMID- 24284599
TI  - Dynamic visual acuity (DVA) during locomotion for targets at near and far
      distances: effects of aging, walking speed and head-trunk coupling.
AB  - This study examined effects of aging, head-trunk coupling (HTcoupling) and
      walking speed on dynamic visual acuity (DVA) at near and far viewing distances.
      Ten healthy participants were recruited in 3 groups; young: 20-33 years, Older1:
      65-74 years, Older2: 75-85 years. The binocular DVA was measured while walking on
      a treadmill at 0.75 and 1.5 m/s speeds. The optotype display was placed at 0.5 m
      for NearDVA and at 3.0 m for FarDVA. On randomly selected trials, HTcoupling was
      achieved by using a collar. A mix-factor ANOVA (age-group x HTcoupling x speed)
      was performed separately for the Near and FarDVA. NearDVA declined with
      HTcoupling (p=0.021). Additionally, NearDVA worsened at the faster speed (p<
      0.001). At 1.5 m/s speed the differences between Young and Older2 groups were
      significant (p=0.012) and those between Older1 and Older2 were marginal
      (p=0.085). FarDVA declined at the faster speed (p< 0.001) with no effect of
      HTcoupling or age-group. NearDVA is more sensitive to normal aging process. These
      age-related deficits become more apparent at higher walking speeds. Effect of
      HTcoupling on NearDVA suggests a possible additive effect of insufficient
      dampening of the vertical movement of the overall head-trunk complex and
      inability of the linear vestibulo-ocular reflex to compensate for the consequent
      high discrepancy. 

PMID- 24284600
TI  - Motion sickness susceptibility in healthy subjects and vestibular patients:
      effects of gender, age and trait-anxiety.
AB  - Several studies have suggested that anxiety may play a role in motion sickness
      susceptibility (MSS) variability. This study aimed to assess motion sickness
      susceptibility in healthy subjects and chronic vestibular patients and to
      investigate its relationship to gender, age and trait-anxiety. Healthy subjects
      (n=167) and chronic dizzy patients with various vestibulopathies (n=94), aged
      from 20 to 92 years old, were asked to complete Motion Sickness Susceptibility
      questionnaire (MSSQ) and trait-anxiety questionnaire (STAI-B). When patients were
      divided into those who had vestibular loss (n=51) vs. patients without vestibular
      loss (n=43), the MSSQ scores (mean +/- SD) for patients with vestibular loss
      (18.8 +/- 30.9) were lower than healthy subjects (36.4 +/- 34.8), who were lower
      than vestibular patients without vestibular loss (59.0 +/- 39.7). These
      significant differences could not be explained by gender, age, trait-anxiety, or
      interaction. Women had higher MSS than men, and MSS declined with age for healthy
      subjects and vestibular patients. The overall relationship between anxiety and
      MSS scores was weak and only reached significance in healthy subjects. These
      results support the conclusion that the vestibular system is heavily involved in
      MSS and that trait-anxiety may play a role in MSS but only in healthy subjects. 

PMID- 24284601
TI  - Auditory-pupillary responses in patients with vestibular neuritis.
AB  - Pupillary dilation in response to sound stimuli is well established and generally
      represents a startle reflex to sound. We previously reported that auditory
      pupillary responses (APRs) persist with bilateral deafness, and that the pathways
      mediating APRs involve not only the cochlea but also otolith organs, especially
      the saccule. Here, we evaluated the vestibulo-autonomic responses in vestibular
      neuritis (VN) by assessing APRs. Twelve young healthy volunteers without a
      history of hearing and equilibrium problems and 10 VN patients participated. To
      clarify the relationship between APRs and vestibular function, especially otolith
      function, we performed caloric and vestibular-evoked myogenic response testing on
      VN patients. In normal subjects, we examined APRs when delivering sound stimuli
      to both sides. In VN patients, we examined APRs when delivering stimuli
      simultaneously to both sides, to the affected side alone, and then to the
      unaffected side alone. With binaural stimulation, the pupillary index (PI) - the
      rate of dilation - of VN patients significantly differed from those of normal
      subjects. Moreover, in VN patients, PIs of the affected sides were significantly
      larger than those of the unaffected sides. Our study provides evidence that
      examining APRs may be useful for evaluating vestibulo-autonomic reflexes,
      especially otolith-autonomic reflexes. 

PMID- 24284602
TI  - Ambulatory balance monitoring using a wireless attachable three-axis
      accelerometer.
AB  - BACKGROUND AND OBJECTIVES: The ability of conventional diagnostic equipment to
      monitor feelings of dizziness experienced during daily activities is limited. Our
      goal is to develop an ambulatory multipurpose device for monitoring balance to
      prevent falling in daily life. MATERIALS AND METHODS: A three-axis accelerometers
      and gyroscope sensors were attached to the head, pelvis, and legs of vestibular
      neuritis (VN) patients or age-, height-, and body weight-matched healthy
      volunteers. The sum of the deviations for the scalar value of acceleration
      [signal vector magnitude, SVM (g)] and angular velocity ( degrees /s) was
      measured using the modified Romberg test. RESULTS: The repeated measure ANOVA
      model with acceleration showed a greater group difference (p < 0.001) than that
      with angular velocity (p < 0.01). There was no significant interaction effect
      within-subjects factor between replication and groups (p < 0.178). SVM within the
      VN group significantly increased for all sensor locations compared to the control
      group (p < 0.01). Strong correlations between measurements taken at head and
      pelvis as sensor location were observed for both groups (VN/control,
      r=0.68/r=072). CONCLUS ION: The SVM appears to accurately assess balance while
      standing, even repetitive measurement or any location in body.

PMID- 24284603
TI  - The development of an accelerometer-based measure of human upright static
      anterior- posterior postural sway under various sensory conditions: test-retest
      reliability, scoring and preliminary validity of the Balance Accelerometry
      Measure (BAM).
AB  - BACKGROUND: Accelerometers are being used to assess postural control in adults,
      but there is little to support their reliability and validity. OBJECTIVE: To
      estimate the test-retest reliability of the balance accelerometry measure (BAM)
      and to describe the known-groups validity of the BAM composite score. METHODS:
      Two measures of standing postural sway were taken across six sensory
      (vision/stance surface) and motor stance (feet together or tandem) positions from
      eighteen patients with vestibular disorders and 84 healthy subjects. Test-retest
      reliability for postural sway was estimated across all conditions using
      intraclass correlation coefficient (ICC). A composite measure of sway
      standardized to young healthy subjects on eyes open firm surface stance was
      compared between groups. RESULTS: Test-retest reliability of postural sway was
      good (ICC ? 0.74) under all sensory conditions except eyes closed/tandem stance,
      which was slight to poor. Analysis of the receiver operating characteristic curve
      for composite scores indicated significant accuracy at identification of subjects
      in the vestibular/balance disorder groups. Composite standard scores equal or
      greater than 21.1 identified subjects with vestibular disorders with an accuracy
      of 72% sensitivity and 68% specificity. CONCLUSION: The BAM displays good
      excellent reliability for five of six sensory-motor conditions. The composite
      score appears to differentiate healthy from subjects with vestibular disorders.

PMID- 24284604
TI  - Arm-trunk coordination as a measure of vestibulospinal efficiency.
AB  - When arm and trunk segments are involved in reaching for objects within arm's
      reach, vestibulospinal pathways compensate for trunk motion influence on arm
      movement. This compensatory arm-trunk synergy is characterised by a gain
      coefficient of 0 to 1. Vestibular patients have less efficient arm-trunk
      synergies and lower gains. To assess the clinical usefulness of the gain measure,
      we used a portable ultrasound-based device to characterize arm-trunk coordination
      deficits in vestibular patients. Arm-trunk coordination without vision was
      measured in a Stationary Hand Task where hand position was maintained during
      trunk movement, and a Reaching Task with and without trunk motion. Twenty
      unilateral vestibular patients and 16 controls participated. For the Stationary
      Hand task, patient gains ranged from g=0.94 (good compensation) to 0.31 (poor
      compensation) and, on average, were lower than in controls (patients: 0.67 +/-
      0.19; controls: 0.85 +/- 0.07; p< 0.01). Gains were significantly correlated with
      clinical tests (Sensory Organization; r=0.62, p< 0.01, Foam Romberg Eyes Closed;
      r=0.65, p< 0.01). For the Reaching Task, blocking trunk movement during reaching
      modified hand position significantly more in patients (8.2 +/- 4.3 cm) compared
      to controls (4.5 +/- 1.7 cm, p< 0.02) and the amount of hand position deviation
      was correlated with the degree of vestibular loss in a sub-group (n=14) of
      patients. Measurement of the Stationary Task arm-trunk gain and hand deviations
      during the Reaching Task can help characterize sensorimotor problems in
      vestibular-deficient patients and track recovery following therapeutic
      interventions. The ultrasound-based portable device is suitable for measuring
      vestibulospinal deficits in arm-trunk coordination in a clinical setting. 

PMID- 24284605
TI  - The diagnostic value of vestibular evoked myogenic potentials in patients with
      Meniere's disease.
AB  - OBJECTIVE: To estimate the sensitivity and specificity of vestibular evoked
      myogenic potentials (VEMPs) in comparison with caloric test in diagnosing
      Meniere's disease (MD) among patients with dizziness. METHODS: Data were
      retrospectively collected from 1,170 consecutive patients who underwent
      vestibular tests. Among them, 114 patients were diagnosed as having unilateral
      definite MD. VEMPs in response to clicks and short tone burst stimulation as well
      as caloric tests were performed. The sensitivity and specificity of each test
      were evaluated. The results of each test were compared with hearing level and
      staging of MD. RESULTS: The sensitivity and specificity of VEMPs were 50.0% and
      48.9%, while those of the caloric test were 37.7% and 51.2%, respectively. There
      was no significant difference in hearing level between patients appropriately or
      inappropriately identified by VEMPs, whereas there was a significant difference
      in those of the caloric test. Combined use of VEMP and caloric test increased the
      sensitivity to 65.8%. CONCLUSION: Although the sensitivity and specificity of
      VEMPs in diagnosing MD were not high, they were comparable to those of caloric
      test. VEMPs as well as caloric testing may give additional information as part of
      a diagnostic test battery for detecting vestibular abnormalities in MD.

PMID- 24284606
TI  - Vestibular rehabilitation in acute central vestibulopathy: a randomized
      controlled trial.
AB  - OBJECTIVE: To investigate the effects of two different rehabilitation programs in
      acute central vestibulopathy secondary to posterior circulation stroke. METHOD: A
      prospective randomized controlled study was conducted on 25 patients with
      posterior circulation stroke. Patients were instructed in routine balance and
      mobility exercises during the acute hospitalization period. At discharge,
      patients were assigned to either a rehabilitation or home exercise group. The
      home exercise group was instructed to perform the same exercise program provided
      in the course of hospitalization period. The rehabilitation group was randomized
      into the visual feedback posturography training or vestibular rehabilitation
      group. The balance and gait performance were assessed with clinical and objective
      measurements before and after 6 weeks of training. RESULTS: The balance and gait
      scores were significantly improved in both rehabilitation groups and in the home
      exercise group (p< 0.05), but no significant difference was found between the
      groups in terms of post-treatment values (p> 0.05). CONCLUSION: The improvements
      of balance and gait function in rehabilitation groups did not differ from the
      home exercise group. Rehabilitation programs were equally effective to improve
      the recovery in acute central vestibulopathy.

PMID- 24284607
TI  - Tunable giant anisotropic diffusion of water sub-monolayers between graphene
      layers.
AB  - We investigate the in-plane confinement effect of two graphene layers on the
      diffusion behaviour of water sub-monolayers using molecular dynamics simulations.
      An unexpected fast diffusion state with giant anisotropy is observed when the two
      confining graphene walls have certain shifts applied to their relative positions.
      The phenomenon is mainly attributed to the smooth one-dimensional potential
      channels produced by the composition effect of the potential energy landscapes of
      the two graphene walls, and the concerted motion of water molecules due to
      hydrogen bonding. Unique duality in the diffusion mechanism is observed in the
      fast diffusion state, as is ballistic motion along the potential channels and
      Fickian diffusion across such channels. The smooth potential channels can be
      created in certain directions simply by shifting the confining walls, which
      provides a novel measure to manipulate the motion of confined molecules in real
      time. 

PMID- 24284608
TI  - Exclusive breastfeeding and developmental and behavioral status in early
      childhood.
AB  - Breastfeeding during infancy may have beneficial effects on various developmental
      outcomes in childhood. In this study, exclusively breastfed infants were randomly
      assigned to receive complementary foods from the age of 4 months in addition to
      breast milk (CF, n = 60), or to exclusively breastfeed to 6 months (EBF, n = 59).
      At 18 months and again at 30-35 months of age, the children were evaluated with
      the Parent's Evaluation of Developmental Status questionnaire (PEDS) and the
      Brigance Screens-II. The parents completed the PEDS questionnaire at both time
      intervals and the children underwent the Brigance Screens-II at 30-35 months. At
      30-35 months, no significant differences were seen in developmental scores from
      the Brigance screening test (p = 0.82). However, at 30-35 months a smaller
      percentage of parents in group CF (2%) had concerns about their children's gross
      motor development compared to those in group EBF (19%; p = 0.01), which remained
      significant when adjusted for differences in pre-randomization characteristics (p
      = 0.03). No sustained effect of a longer duration of exclusive breastfeeding was
      seen on selected measures of developmental and behavioral status at 18 months,
      although at 30-35 months, a smaller percentage of parents of children introduced
      to complementary foods at four months of age expressed concerns about their gross
      motor development. 

PMID- 24284609
TI  - The effects of multivitamin supplementation on diurnal cortisol secretion and
      perceived stress.
AB  - Recent evidence suggests that dietary intake of vitamins, in particular the B
      vitamins including B6, B9 and B12 may have a number of positive effects on mood
      and stress. Given the effects of stress on a range of biological mechanisms
      including the endocrine system, it could be reasonably expected that multivitamin
      supplementation may also affect markers of these mechanisms such as diurnal
      cortisol secretion. In the current double-blind placebo-controlled study 138
      adults (aged 20 to 50 years) were administered a multivitamin containing B
      vitamins versus placebo over a 16-week period. Salivary cortisol measurements
      were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16
      weeks. Perceived Stress (PSS) was measured at baseline, 8-weeks and 16-weeks,
      while blood serum measures of B6, B12 and homocysteine (HCy) as well as red cell
      folate (B9) were also collected at these time points. A significant interaction
      was found between treatment group and study visit for the Cortisol Awakening
      Response (CAR). Compared to placebo, at 16-weeks multivitamin supplementation was
      found to be associated with a near-significant trend towards an increased CAR. No
      significant differences in PSS were found between groups, with PSS increasing in
      both groups across the course of the study. Red cell folate was found to be
      significantly correlated with the CAR response at 16-weeks while HCy levels were
      not found to be associated with the CAR response, although HCy significantly
      correlated with waking cortisol levels at 8-weeks. A possible interpretation of
      the elevation in CAR associated with multivitamin supplementation is that this
      represents an adaptive response to everyday demands in healthy participants. 

PMID- 24284610
TI  - A randomised cross-over pharmacokinetic bioavailability study of synthetic versus
      kiwifruit-derived vitamin C.
AB  - Kiwifruit are a rich source of vitamin C and also contain numerous
      phytochemicals, such as flavonoids, which may influence the bioavailability of
      kiwifruit-derived vitamin C. The aim of this study was to compare the relative
      bioavailability of synthetic versus kiwifruit-derived vitamin C using a
      randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged
      18-35 years) received either a chewable tablet (200 mg vitamin C) or the
      equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting
      blood and urine were collected half hourly to hourly over the eight hours
      following intervention. The ascorbate content of the plasma and urine was
      determined using HPLC with electrochemical detection. Plasma ascorbate levels
      increased from 0.5 h after the intervention (P = 0.008). No significant
      differences in the plasma time-concentration curves were observed between the two
      interventions (P = 0.645). An estimate of the total increase in plasma ascorbate
      indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived
      vitamin C. There was an increase in urinary ascorbate excretion, relative to
      urinary creatinine, from two hours post intervention (P < 0.001). There was also
      a significant difference between the two interventions, with enhanced ascorbate
      excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was
      calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and
      kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown
      comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic
      vitamin C. 

PMID- 24284611
TI  - Selected dietary nutrients and the prevalence of metabolic syndrome in adult
      males and females in Saudi Arabia: a pilot study.
AB  - During the last decade, the rapid economic development in Saudi Arabia resulted
      in an unbalanced dietary intake pattern within the general population.
      Consequently, metabolic syndrome was also documented to be highly prevalent in
      the Middle-East region. We aimed to examine the relationship between selected
      dietary nutrient intakes and the prevalence of metabolic syndrome in the general
      adult population of Riyadh, Saudi Arabia. In this cross-sectional study, 185
      adult Saudis aged 19 to 60 years (87 males and 98 females (mean age 35.6 +/- 13.2
      and 37.6 +/- 11.7 years, respectively)) were included. The criteria for metabolic
      syndrome were based on the International Diabetes Foundation (IDF) criteria, and
      the dietary food intake was assessed by two 24-h dietary recall methods. The odd
      ratios (ORs) of metabolic syndrome risk across quartiles of selected dietary
      nutrients were significantly lower for carbohydrates and proteins, as well as for
      vitamins A, C, E and K, calcium, zinc and magnesium (p < 0.05 for all) in the
      female group with metabolic syndrome than those without. The pattern of daily
      dietary intake of selected nutrients among the general population of Saudi Arabia
      raises concern, and this dietary imbalance could increase the risk of metabolic
      syndrome, particularly in adult Saudi females. 

PMID- 24284612
TI  - Assessing quality outcome measures in children with coeliac disease--experience
      from two UK centres.
AB  - Improved diagnosis of coeliac disease has increased incidence and therefore
      burden on the health care system. There are no quality outcome measures (QOM) in
      use nationally to assess hospital management of this condition. This study
      applied QOM devised by the East of England paediatric gastroenterology network to
      99 patients reviewed at two tertiary hospitals in the Network, to assess the
      quality of care provided by nurse led and doctor led care models. The average
      performance across all QOM was 96.2% at Addenbrooke's Hospital (AH), and 98.7% at
      Norfolk and Norwich Hospital (NNUH), whilst 95% (n = 18) of QOM were met. Patient
      satisfaction was high at both sites (uptake of questionnaire 53 of 99 patients in
      the study). The study showed a comparably high level of care delivered by both a
      nurse and doctor led service. Our quality assessment tools could be applied in
      the future by other centres to measure standards of care. 

PMID- 24284613
TI  - The clinical response to gluten challenge: a review of the literature.
AB  - The aim of this review was to identify, evaluate and summarize all relevant
      studies reporting on the clinical response to gluten challenge by adult or
      pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten
      free diet. We evaluated the effect of gluten challenge on changes in symptoms,
      intestinal mucosa histology, and serum antibodies. A systematic electronic search
      was performed for studies published as of 1966 using PubMed and Scopus databases.
      In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or
      comprised a gluten-containing diet. The onset of symptoms upon gluten intake
      varied largely from days to months and did not parallel serum antibody or
      histological changes. Within 3 months of gluten challenge, 70%-100% of pediatric
      CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%-70% for
      AGA-IgG. A limited number of trials suggest that no more than half of adult
      patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers.
      Approximately 50%-100% of pediatric and adult patients experienced mucosal
      relapse of gluten provocation within 3 months, which was preceded by increased
      mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month
      high-dose gluten challenge should be suitable to diagnose the majority of CD
      patients. In some cases prolonged challenge may be needed to verify diagnosis.
      Combination testing for antibodies and mucosal histology may fasten the
      diagnosis. 

PMID- 24284614
TI  - "Jello(r) shots" and cocktails as ethanol vehicles: parametric studies with high-
      and low-saccharin-consuming rats.
AB  - Naive humans and rats voluntarily consume little ethanol at concentrations above
      ~6% due to its aversive flavor. Developing procedures that boost intake of
      ethanol or ethanol-paired flavors facilitates research on neural mechanisms of
      ethanol-associated behaviors and helps identify variables that modulate ethanol
      intake outside of the lab. The present study explored the impact on consumption
      of ethanol and ethanol-paired flavors of nutritionally significant parametric
      variations: ethanol vehicle (gelatin or solution, with or without polycose);
      ethanol concentration (4% or 10%); and feeding status (chow deprived or ad lib.)
      during flavor conditioning and flavor preference testing. Individual differences
      were modeled by testing rats of lines selectively bred for high (HiS) or low
      (LoS) saccharin intake. A previously reported preference for ethanol-paired
      flavors was replicated when ethanol had been drunk during conditioning. However,
      indifference or aversion to ethanol-paired flavors generally obtained when
      ethanol had been eaten in gelatin during conditioning, regardless of ethanol
      concentration, feeding status, or caloric value of the vehicle. Modest sex and
      line variations occurred. Engaging different behavioral systems when eating
      gelatin, rather than drinking solution, may account for these findings.
      Implications for parameter selection in future neurobiological research and for
      understanding conditions that influence ethanol intake outside of the lab are
      discussed. 

PMID- 24284615
TI  - Oral zinc supplementation for the treatment of acute diarrhea in children: a
      systematic review and meta-analysis.
AB  - Evidence supporting the impact of therapeutic zinc supplementation on the
      duration and severity of diarrhea among children under five is largely derived
      from studies conducted in South Asia. China experiences a substantial portion of
      the global burden of diarrhea, but the impact of zinc treatment among children
      under five has not been well documented by previously published systematic
      reviews on the topic. We therefore conducted a systematic literature review,
      which included an exhaustive search of the Chinese literature, in an effort to
      update previously published estimates of the effect of therapeutic zinc. We
      conducted systematic literature searches in various databases, including the
      China National Knowledge Infrastructure (CNKI), and abstracted relevant data from
      studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool
      select outcomes and to generate estimates of percentage difference and relative
      risk comparing outcomes between zinc and control groups. We identified 89 Chinese
      and 15 non-Chinese studies for the review, including studies in 10 countries from
      all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469
      zinc and 9353 control). None of the included Chinese studies had previously been
      included in published pooled effect estimates. Chinese and non-Chinese studies
      reported the effect of therapeutic zinc supplementation on decreased episode
      duration, stool output, stool frequency, hospitalization duration and proportion
      of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese
      studies yielded an overall 26% (95% CI: 20%-32%) reduction in the estimated
      relative risk of diarrhea lasting beyond three days among zinc-treated children.
      Studies conducted in and outside China report reductions in morbidity as a result
      of oral therapeutic zinc supplementation for acute diarrhea among children under
      five years of age. The WHO recommendation for zinc treatment of diarrhea episodes
      should be supported in all low- and middle-income countries. 

PMID- 24284616
TI  - External mill monitoring of wheat flour fortification programs: an approach for
      program managers using experiences from Jordan.
AB  - The fortification of wheat flour with micronutrients is a common strategy to
      increase vitamin and mineral intake. While wheat flour mills are often inspected
      by agencies affiliated with national ministries to ensure compliance with
      national fortification standards, few countries use data derived from these
      inspections to construct an external monitoring system for use in program
      management and evaluation. The primary objective of this paper is to assess the
      performance of the external monitoring system utilized in Jordan according to the
      US Centers for Disease Control and Prevention's Updated Guidelines for Evaluating
      Public Health Surveillance Systems. A secondary objective is to present mill
      monitoring results from 2009 to 2010 in order to demonstrate the data generated
      by the system. The review concludes that the data required for the system is
      representative, simple to collect, and can be collected in a flexible manner. The
      external monitoring system is acceptable to participating agencies and millers
      and is stable due to mandatory fortification legislation which provides the legal
      framework for external monitoring. Data on production of fortified flour and
      utilization of premix can be provided in a timely manner, but on-site mill
      monitoring and flour sample collection are more challenging due to resource
      constraints. The frequent collection of a small number of indicators can provide
      fortification program managers with timely information with which to base
      decisions. Jordan's external monitoring system successfully documented the
      performance of each mill and the entire flour fortification program, and can
      serve as a model for other national fortification programs considering external
      monitoring approaches. 

PMID- 24284617
TI  - Folate deficiency and folic acid supplementation: the prevention of neural-tube
      defects and congenital heart defects.
AB  - Diet, particularly vitamin deficiency, is associated with the risk of birth
      defects. The aim of this review paper is to show the characteristics of common
      and severe neural-tube defects together with congenital heart defects (CHD) as
      vitamin deficiencies play a role in their origin. The findings of the Hungarian
      intervention (randomized double-blind and cohort controlled) trials indicated
      that periconceptional folic acid (FA)-containing multivitamin supplementation
      prevented the major proportion (about 90%) of neural-tube defects (NTD) as well
      as a certain proportion (about 40%) of congenital heart defects. Finally the
      benefits and drawbacks of three main practical applications of folic
      acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional
      supplementation; and (iii) flour fortification are discussed. The conclusion
      arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of
      prevention is better than a pound of care". 

PMID- 24284618
TI  - Sublingual nucleotides prolong run time to exhaustion in young physically active
      men.
AB  - Although dietary nucleotides have been determined to be required for normal
      immune function, there is limited direct interventional evidence confirming
      performance-enhancing effects of sublingual nucleotides in humans. A double
      blind, placebo-controlled, randomized trial was conducted to evaluate the effect
      of sublingual nucleotides (50 mg/day) administered for 14 days in thirty young
      healthy physically active males, on endurance performance and immune responses.
      Fasting white blood cell count, natural killer cells (NKC) number, NKC cytotoxic
      activity, and serum immunoglobulin (IgA, IgM, IgG), and time to exhaustion, peak
      rate of perceived exertion, peak heart rate, and peak running speed during the
      exercise test were measured at baseline (day 0) and post-intervention (day 14).
      Time to exhaustion, as well as serum immunoglobulin A and NKC cytotoxic activity,
      were significantly higher at day 14 (p < 0.05) in participants supplemented with
      nucleotides compared with those who consumed placebo. No significant differences
      in other parameters were observed between groups at post-intervention. No
      volunteers withdrew before the end of the study nor reported any vexatious side
      effects of supplementation. The results of the present study suggest that
      sublingual nucleotides may provide pertinent benefit as both an ergogenic and
      immunostimulatory additive in active males. 

PMID- 24284620
TI  - Radiation therapy for advanced and metastatic melanoma.
AB  - Radiation therapy (RT) is an important modality in cancer treatment. However, the
      general perception is that melanoma is radio-resistant. High quality clinical
      trials are helping to establish the place of RT in select scenarios of advanced
      disease at primary, regional, and distant sites. New RT techniques need to be
      integrated with effective new systemic therapies within a multidisciplinary
      environment to ensure optimum patient outcomes. It is important that radiation
      oncologists embrace this opportunity.

PMID- 24284619
TI  - Bone mass and mineral metabolism alterations in adult celiac disease:
      pathophysiology and clinical approach.
AB  - Osteoporosis affects many patients with celiac disease (CD), representing the
      consequence of calcium malabsorption and persistent activation of mucosal
      inflammation. A slight increase of fracture risk is evident in this condition,
      particularly in those with overt malabsorption and in postmenopausal state. The
      adoption of a correct gluten-free diet (GFD) improves bone derangement, but is
      not able to normalize bone mass in all the patients. Biomarkers effective in the
      prediction of bone response to gluten-free diet are not yet available and the
      indications of guidelines are still imperfect and debated. In this review, the
      pathophysiology of bone loss is correlated to clinical aspects, defining an
      alternative proposal of management for this condition. 

PMID- 24284621
TI  - Broadband evolution of phononic-crystal-waveguide eigenstates in real- and k
      spaces.
AB  - Control of sound in phononic band-gap structures promises novel control and
      guiding mechanisms. Designs in photonic systems were quickly matched in
      phononics, and rows of defects in phononic crystals were shown to guide sound
      waves effectively. The vast majority of work in such phononic guiding has been in
      the frequency domain, because of the importance of the phononic dispersion
      relation in governing acoustic confinement in waveguides. However, frequency
      domain studies miss vital information concerning the phase of the acoustic field
      and eigenstate coupling. Using a wide range of wavevectors k, we implement an
      ultrafast technique to probe the wave field evolution in straight and L-shaped
      phononic crystal surface-phonon waveguides in real- and k-space in two spatial
      dimensions, thus revealing the eigenstate-energy redistribution processes and the
      coupling between different frequency-degenerate eigenstates. Such use of k-t
      space is a first in acoustics, and should have other interesting applications
      such as acoustic-metamaterial characterization. 

PMID- 24284623
TI  - Stem cells: Dual response to Ras mutation.

PMID- 24284624
TI  - Cancer: Discrepancies in drug sensitivity.

PMID- 24284625
TI  - N6-methyladenosine-dependent regulation of messenger RNA stability.
AB  - N(6)-methyladenosine (m(6)A) is the most prevalent internal (non-cap)
      modification present in the messenger RNA of all higher eukaryotes. Although
      essential to cell viability and development, the exact role of m(6)A modification
      remains to be determined. The recent discovery of two m(6)A demethylases in
      mammalian cells highlighted the importance of m(6)A in basic biological functions
      and disease. Here we show that m(6)A is selectively recognized by the human YTH
      domain family 2 (YTHDF2) 'reader' protein to regulate mRNA degradation. We
      identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs,
      but which also include non-coding RNAs, with a conserved core motif of G(m(6)A)C.
      We further establish the role of YTHDF2 in RNA metabolism, showing that binding
      of YTHDF2 results in the localization of bound mRNA from the translatable pool to
      mRNA decay sites, such as processing bodies. The carboxy-terminal domain of
      YTHDF2 selectively binds to m(6)A-containing mRNA, whereas the amino-terminal
      domain is responsible for the localization of the YTHDF2-mRNA complex to cellular
      RNA decay sites. Our results indicate that the dynamic m(6)A modification is
      recognized by selectively binding proteins to affect the translation status and
      lifetime of mRNA. 

PMID- 24284626
TI  - Inconsistency in large pharmacogenomic studies.
AB  - Two large-scale pharmacogenomic studies were published recently in this journal.
      Genomic data are well correlated between studies; however, the measured drug
      response data are highly discordant. Although the source of inconsistencies
      remains uncertain, it has potential implications for using these outcome measures
      to assess gene-drug associations or select potential anticancer drugs on the
      basis of their reported results. 

PMID- 24284627
TI  - Oncogenic Nras has bimodal effects on stem cells that sustainably increase
      competitiveness.
AB  - 'Pre-leukaemic' mutations are thought to promote clonal expansion of
      haematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness;
      however, mutations that increase HSC proliferation tend to reduce competitiveness
      and self-renewal potential, raising the question of how a mutant HSC can
      sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent
      in human myeloproliferative neoplasms and leukaemia. Here we show that a single
      allele of oncogenic Nras(G12D) increases HSC proliferation but also increases
      reconstituting and self-renewal potential upon serial transplantation in
      irradiated mice, all prior to leukaemia initiation. Nras(G12D) also confers long
      term self-renewal potential to multipotent progenitors. To explore the mechanism
      by which Nras(G12D) promotes HSC proliferation and self-renewal, we assessed cell
      cycle kinetics using H2B-GFP label retention and 5-bromodeoxyuridine (BrdU)
      incorporation. Nras(G12D) had a bimodal effect on HSCs, increasing the frequency
      with which some HSCs divide and reducing the frequency with which others divide.
      This mirrored bimodal effects on reconstituting potential, as rarely dividing
      Nras(G12D) HSCs outcompeted wild-type HSCs, whereas frequently dividing
      Nras(G12D) HSCs did not. Nras(G12D) caused these effects by promoting STAT5
      signalling, inducing different transcriptional responses in different subsets of
      HSCs. One signal can therefore increase HSC proliferation, competitiveness and
      self-renewal through bimodal effects on HSC gene expression, cycling and
      reconstituting potential. 

PMID- 24284628
TI  - Retraction: Dance reveals symmetry especially in young men.

PMID- 24284629
TI  - Mutational and fitness landscapes of an RNA virus revealed through population
      sequencing.
AB  - RNA viruses exist as genetically diverse populations. It is thought that
      diversity and genetic structure of viral populations determine the rapid
      adaptation observed in RNA viruses and hence their pathogenesis. However, our
      understanding of the mechanisms underlying virus evolution has been limited by
      the inability to accurately describe the genetic structure of virus populations.
      Next-generation sequencing technologies generate data of sufficient depth to
      characterize virus populations, but are limited in their utility because most
      variants are present at very low frequencies and are thus indistinguishable from
      next-generation sequencing errors. Here we present an approach that reduces next
      generation sequencing errors and allows the description of virus populations with
      unprecedented accuracy. Using this approach, we define the mutation rates of
      poliovirus and uncover the mutation landscape of the population. Furthermore, by
      monitoring changes in variant frequencies on serially passaged populations, we
      determined fitness values for thousands of mutations across the viral genome.
      Mapping of these fitness values onto three-dimensional structures of viral
      proteins offers a powerful approach for exploring structure-function
      relationships and potentially uncovering new functions. To our knowledge, our
      study provides the first single-nucleotide fitness landscape of an evolving RNA
      virus and establishes a general experimental platform for studying the genetic
      changes underlying the evolution of virus populations. 

PMID- 24284630
TI  - Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate
      immunity.
AB  - The type I interferon (IFN) response protects cells from viral infection by
      inducing hundreds of interferon-stimulated genes (ISGs), some of which encode
      direct antiviral effectors. Recent screening studies have begun to catalogue ISGs
      with antiviral activity against several RNA and DNA viruses. However, antiviral
      ISG specificity across multiple distinct classes of viruses remains largely
      unexplored. Here we used an ectopic expression assay to screen a library of more
      than 350 human ISGs for effects on 14 viruses representing 7 families and 11
      genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance
      virus infectivity. Comparative analysis reveals that the screened ISGs target
      positive-sense single-stranded RNA viruses more effectively than negative-sense
      single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor
      cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression
      also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of
      enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral
      program that functions independently of canonical IFN/STAT1 signalling. In vivo,
      genetic ablation of murine cGAS reveals its requirement in the antiviral response
      to two DNA viruses, and an unappreciated contribution to the innate control of an
      RNA virus. These studies uncover new paradigms for the preferential specificity
      of IFN-mediated antiviral pathways spanning several virus families. 

PMID- 24284632
TI  - DNA-mediated nanoparticle crystallization into Wulff polyhedra.
AB  - Crystallization is a fundamental and ubiquitous process much studied over the
      centuries. But although the crystallization of atoms is fairly well understood,
      it remains challenging to predict reliably the outcome of molecular
      crystallization processes that are complicated by various molecular interactions
      and solvent involvement. This difficulty also applies to nanoparticles: high
      quality three-dimensional crystals are mostly produced using drying and
      sedimentation techniques that are often impossible to rationalize and control to
      give a desired crystal symmetry, lattice spacing and habit (crystal shape). In
      principle, DNA-mediated assembly of nanoparticles offers an ideal opportunity for
      studying nanoparticle crystallization: a well-defined set of rules have been
      developed to target desired lattice symmetries and lattice constants, and the
      occurrence of features such as grain boundaries and twinning in DNA superlattices
      and traditional crystals comprised of molecular or atomic building blocks
      suggests that similar principles govern their crystallization. But the presence
      of charged biomolecules, interparticle spacings of tens of nanometres, and the
      realization so far of only polycrystalline DNA-interconnected nanoparticle
      superlattices, all suggest that DNA-guided crystallization may differ from
      traditional crystal growth. Here we show that very slow cooling, over several
      days, of solutions of complementary-DNA-modified nanoparticles through the
      melting temperature of the system gives the thermodynamic product with a specific
      and uniform crystal habit. We find that our nanoparticle assemblies have the
      Wulff equilibrium crystal structure that is predicted from theoretical
      considerations and molecular dynamics simulations, thus establishing that DNA
      hybridization can direct nanoparticle assembly along a pathway that mimics atomic
      crystallization. 

PMID- 24284631
TI  - Targeting Plasmodium PI(4)K to eliminate malaria.
AB  - Achieving the goal of malaria elimination will depend on targeting Plasmodium
      pathways essential across all life stages. Here we identify a lipid kinase,
      phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a
      new antimalarial compound class that inhibits the intracellular development of
      multiple Plasmodium species at each stage of infection in the vertebrate host.
      Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission
      blocking activity in rodent malaria models, are active against blood-stage field
      isolates of the major human pathogens P. falciparum and P. vivax, and inhibit
      liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that
      imidazopyrazines exert their effect through inhibitory interaction with the ATP
      binding pocket of PI(4)K, altering the intracellular distribution of
      phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key
      Plasmodium vulnerability, opening up new avenues of target-based discovery to
      identify drugs with an ideal activity profile for the prevention, treatment and
      elimination of malaria. 

PMID- 24284633
TI  - Allergic transfusion reaction caused by the shrimp allergen of donor blood: a
      case report.
AB  - OBJECTIVE: The purpose of this report is to analyze the cause of allergic
      transfusion reaction. METHODS: The methods of immunoblot and immunonephelometry
      were applied to detect the levels of the immunoglobulins of IgA (Immunoglobulin
      A) and IgE (Immunoglobulin E) and the level of sIgE (specific Immunoglobulin E)
      to shrimp allergen both in the patient's pre and post transfusion blood samples,
      respectively. RESULTS: After transfusion, The level of sIgE to shrimp showed
      "increase" corresponding to the concentration of 0.70-3.5 IU/ml. CONCLUSION: The
      allergic transfusion reaction was very likely caused by passive transfer of
      shrimp antigen to the patient allergic to shrimp.

PMID- 24284634
TI  - The role of early life stress in adult psychiatric disorders: a systematic review
      according to childhood trauma subtypes.
AB  - Early life stress (ELS; sexual abuse, physical abuse, emotional abuse, physical
      neglect, and emotional neglect) has been the focus of numerous studies. It has
      been associated with the onset and the severity of psychiatric disorders in
      adults. The objective of this study was to review the literature on ELS
      associated with psychiatric disorders in adulthood, seeking to identify whether
      there are independent effects between subtypes of early stress in triggering
      psychopathology in adults. We reviewed articles from 2001 to 2011 in four
      databases (PubMed, SciELO, LILACS, and PsycINFO), with the following key words:
      child abuse, maltreatment, early life stress, psychiatric disorders, mental
      disease, and psychopathology. Forty-four articles were selected, and most of
      these articles demonstrate that the subtypes of ELS are associated with several
      psychiatric disorders, more specifically: physical abuse, sexual abuse, and
      unspecified neglect with mood disorders and anxiety disorders; emotional abuse
      with personality disorders and schizophrenia; and physical neglect with
      personality disorders. Physical neglect had the weakest association between the
      subtypes. ELS subtypes in childhood and adolescence can predict the development
      of psychopathology in adults. Scientific evidence shows that ELS triggers,
      aggravates, maintains, and increases the recurrence of psychiatric disorders.
      These results demonstrate the importance of a deeper understanding about the
      unique effects of ELS subtypes, especially for mental health professionals. 

PMID- 24284635
TI  - Risk factors of violence during a 4-week period in a psychiatric outpatient
      population.
AB  - The clinical impact of structured risk assessment instruments has been limited by
      a lack of information regarding a) their short-term accuracy and b) the
      relationship between change as measured by the instrument and a change in the
      risk for harm. Data were collected every 4 weeks on a) variables designed to
      resemble the items of a structured risk assessment instrument, b) substance use,
      c) social circumstances and mental state, and d) violent behavior. Scores on the
      variables designed to resemble the items of a risk assessment instrument were
      associated with violence during the ensuing 4 weeks. However, an increase in a
      subject's score on these variables was not associated with violence. Instead,
      increasing cocaine use and increasing social conflict as described by the subject
      at interview were associated with violence during those weeks. 

PMID- 24284636
TI  - Phenomenology of borderline personality disorder: the role of race and
      socioeconomic status.
AB  - Little is known about racial differences in borderline personality disorder (BPD)
      that may influence etiology, phenomenology, and treatment of women with BPD. A
      total of 83 women with BPD participated in this cross-sectional study: n = 41
      white and n = 42 African-American women. Structured interviews were used to
      assess Axis I and II disorders, and a series of interviews and questionnaires
      captured internalizing and externalizing symptoms. The white women with BPD
      reported more severe internalizing symptoms, whereas the African-American women
      reported more severe externalizing symptoms. Except for the association between
      race and number of suicide attempts, the relationship between race and
      internalizing/externalizing symptoms was mediated by socioeconomic status. In
      conclusion, African-American women with BPD may present with more severe symptoms
      of lack of anger control and fewer suicidal behaviors than those of white women
      with BPD, raising the possibility that they are misdiagnosed and receive
      treatments that are not optimal for BPD. 

PMID- 24284637
TI  - Military mental health: the role of daily hassles while deployed.
AB  - This study sought to identify factors contributing to symptoms of depression and
      posttraumatic stress disorder (PTSD) in recently deployed combat veterans. A
      sample of 168 active duty military personnel completed measures of combat
      exposure, deployment-related daily hassles, depression symptoms, and PTSD
      symptoms at six time points across their deployment: predeployment and 1, 3, 6,
      and 12 months postdeployment. Mixed-effects linear modeling with repeated
      measures was used to identify factors associated with depression and PTSD
      severity over time. Postdeployment depression severity did not change over time,
      but PTSD severity decreased slightly over time after returning home.
      Postdeployment depression severity was predicted by past (but not recent) combat
      exposure, daily hassles, and concurrent PTSD symptoms. Postdeployment PTSD
      severity was predicted by past and recent combat exposure, concurrent depression
      symptoms, and male sex. Depression severity mediated the relationship between
      daily hassles and postdeployment PTSD severity. 

PMID- 24284638
TI  - Posttraumatic stress disorder in a Serbian community: seven years after trauma
      exposure.
AB  - Posttraumatic stress disorder (PTSD) may develop as a serious long-term
      consequence of traumatic experiences, even many years after trauma exposure. The
      objectives of this study were to examine the prevalence of lifetime and current
      PTSD as well as to detect the most stressful life events and sociodemographic
      risk factors of PTSD in a general adult Serbian population. The sample consisted
      of 640 subjects chosen by random walk technique in five regions of the country.
      The Mini International Neuropsychiatric Interview 5 revealed an 18.8% prevalence
      rate of current PTSD and a 32.3% prevalence rate of lifetime PTSD. According to
      the Life Stressor Checklist-Revised, the bombardment, being expelled from home,
      siege, and participation in combat were the stressful events most likely to be
      associated with PTSD. The prevalence of PTSD increased among widows and widowers,
      divorced persons, unemployed persons, and retired persons. The high level of PTSD
      a few years after the trauma exposure classifies as a significant health problem
      that can cause serious consequences for families and the community as a whole. 

PMID- 24284639
TI  - Risk factors of posttraumatic stress disorder after an earthquake disaster.
AB  - This study sought to predict posttraumatic stress disorder (PTSD) from women's
      reproductive health events after an earthquake experience. Data on antenatal
      care, pregnancy outcomes, family planning, socioeconomic status, earthquake
      experiences, and mental health were collected from a random sample of 425 women
      of reproductive age using the Centers for Disease Control and Prevention
      Reproductive Health Assessment Toolkit and the Harvard Trauma Questionnaire. Data
      were analyzed using multivariate regression analysis to predict PTSD symptoms
      from posttrauma care variables and reproductive health events. Restricted social
      participation, use of temporary accommodation, pregnancy complications, and use
      of injectable contraceptives were significant risk factors of PTSD. These factors
      may be exacerbated by the social context of conservative societies, traditions
      about health care-seeking behavior, and access to health care. Antecedent
      reproductive health events influence women's reaction to major trauma including
      events such as an earthquake. 

PMID- 24284640
TI  - Prevalence of psychotic-like experiences in young adults with social anxiety
      disorder and correlation with affective dysregulation.
AB  - Social anxiety disorder (SAD) is associated with psychotic-like experiences
      (PLEs) and is a frequent diagnosis in the prodromal phases of psychosis. We
      investigated whether psychopathological factors could discriminate which subjects
      with SAD are more likely to develop PLEs. A sample of 128 young adults with SAD
      was split into two subsamples according to the presence of clinically relevant
      PLEs. Correlations between PLEs and other psychopathological markers were
      explored. The SAD with PLEs group showed higher level of anxiety, depression, and
      intolerance of uncertainty (IU) compared with the SAD without PLEs group. A
      limitation of this study is that the cross-sectional design precluded the
      analysis of causality. In our sample, the presence of PLEs is related to higher
      levels of depression, anxiety, and IU. The current findings are consistent with
      hypotheses suggesting that cognitive disturbances, together with social anxiety,
      may result in PLEs. 

PMID- 24284641
TI  - Anxiety disorders and rapid cycling: data from a cohort of 8129 youths with
      bipolar disorder.
AB  - Anxiety disorders (ADs) are common in youths with bipolar disorder (BD). We
      examine psychiatric comorbidity, hospitalization, and treatment in youths with
      versus without AD and rapid cycling (four or more cycles per year). Data from the
      Integrated Healthcare Information Services cohort were used and included 8129
      youths (ages <=18 years). Prevalence of AD, demographic, type of AD,
      hospitalization, and use of psychotropics were compared between rapid and
      nonrapid cycling. Overall, 51% of the youths met criteria for at least one
      comorbid AD; they were predominantly female and were between 12 and 17 years of
      age. The most common comorbid ADs were generalized ADs and separation ADs. In the
      patients with rapid cycling, 65.5% met criteria for comorbid AD. The BD youths
      with AD were more likely to have major depressive disorders and other comorbid
      ADs, to be given more psychotropics, and to be hospitalized for depression and
      medical conditions more often than were those without AD. 

PMID- 24284642
TI  - Attitudes toward life and death and suicidality among inpatient female
      adolescents with eating disorders.
AB  - This study investigated whether attitudes about life and death are associated
      with suicidal behavior in eating disorders (EDs). We examined 43 nonsuicidal
      inpatients with EDs, 32 inpatients with EDs who attempted suicide, and 21 control
      participants with scales assessing attitudes to life and death, body-related
      attitudes, core ED symptoms, depression, and anxiety. Both ED groups showed less
      attraction to life and more repulsion from life than did the control
      participants. The suicide attempters showed greater attraction to death, less
      repulsion from death, and more negative attitudes toward their body than did the
      nonsuicidal ED and control participants. Fear of life was associated with
      elevated depression, body-related problems, and childhood sexual abuse.
      Pathological attitudes toward death were associated with greater depression and
      body-related problems. Suicide attempts were found in the inpatients with EDs
      showing binge/purge ED pathology and maladaptive attitudes toward death. This
      study suggests that whereas fear of life is a core feature of an ED, maladaptive
      attitudes toward death appear only in ED patients who have attempted suicide. 

PMID- 24284644
TI  - Body image and noticeable self-inflicted scars.
AB  - Scars from burn injuries have a negative influence on body image. Patients with
      borderline symptoms with nonsuicidal self-injuries (NSSIs), which often result in
      scars, report body image disturbances. We study whether the origin and
      characteristics of scars are associated with body image. Altogether, 125 female
      participants (n = 65 with NSSI) filled in multidimensional body image
      questionnaires. The participants with NSSI reported a significantly more negative
      body image on most subscales compared with the participants with scars of other
      origins. This result remained significant after partialling out scar
      characteristics from regression equations. On a scale assessing body image after
      injuries, a significant correlation with origin of scars was found after
      additionally partialling out body mass index and borderline symptoms. These
      results indicate that self-inflicted scars may adversely affect body image.
      Addressing NSSI, which is relevant in a multitude of disorders, early in
      treatment might help to reduce the extent of scarification and therefore reduce
      the disturbance of body image. 

PMID- 24284643
TI  - Implicit and explicit stigma of mental illness: attitudes in an evidence-based
      practice.
AB  - The extent to which explicit and implicit stigma are endorsed by mental health
      practitioners using evidence-based practices is unknown. The purposes of the
      current study were to a) examine implicit and explicit biases among Assertive
      Community Treatment (ACT) staff and b) explore the extent to which biases
      predicted the use of treatment control mechanisms. Participants were 154 ACT
      staff from nine states. Overall, the participants exhibited positive explicit and
      implicit attitudes toward people with mental illness. When modeled using latent
      factors, greater implicit, but not explicit, bias significantly predicted greater
      endorsement of restrictive or controlling clinical interventions. Thus, despite
      overall positive attitudes toward those with mental illness for the sample as a
      whole, individual differences in provider stigma were related to clinical care.
      Mental health professionals, and specifically ACT clinicians, should be educated
      on types of bias and ways in which biases influence clinical interventions. 

PMID- 24284645
TI  - Predictors of persistent psychotic symptoms in persons with methamphetamine abuse
      receiving psychiatric treatment.
AB  - The objective of this study was to identify predictors of sustained psychotic
      symptoms after methamphetamine (MA) abuse during the course of 6 months from
      patterns of MA and other substance use, depressive symptoms, family history of
      psychosis, antisocial personality disorder, and trauma history. A total of 295
      individuals with MA abuse and psychotic symptoms seeking psychiatric services
      were assessed at baseline and then monthly on symptoms and substance use for 6
      months. Trajectory analyses revealed two trajectories of the individuals with
      positive symptoms, with one group presenting with persistent psychotic symptoms
      (30% of the sample). Those with persistent psychosis were significantly older,
      had more severe psychotic symptoms, misused MA for more years, had more
      antisocial personality traits, and had more sustained depressive symptoms. The
      strongest predictors of belonging to the persistent psychosis group, via logistic
      regressions, were more severe psychotic symptoms, longer use of MA, and sustained
      depressive symptoms. Our results highlight the important comorbidities,
      especially regarding depressive symptoms and persistent psychosis, in individuals
      seeking psychiatric help after MA abuse. This study also highlights the
      importance of identifying people with persistent psychosis within MA users to
      facilitate rapid and effective treatment of co-occurring psychotic disorder. 

PMID- 24284646
TI  - Psychiatrists' and psychologists' practice patterns: different profiles in a
      Spanish clinical sample.
AB  - Important differences in clinical practice exist between psychiatrists and
      psychologists. However, there is scarce information on the characteristics of
      patients receiving treatment from these two groups of professionals. We examined
      the diagnoses assigned to the patients who received treatment from psychiatrists
      and psychologists in outpatient settings of Madrid, Spain, from 1980 to 2008. The
      psychologists were more likely to see anxiety-related disorders, whereas the
      psychiatrists tended to see disorders with a more prominent biological
      underpinning, such as schizophrenia or bipolar disorder. The profile of the
      patients seen by the psychologists is different from that of the psychiatrists.
      Disorders whose development is more related to distress were usually treated by
      the psychologists, whereas disorders with a more prominent biological
      underpinning were usually treated by the psychiatrists. In addition, the dramatic
      increase in the diagnosis of adjustment disorder might be related to the
      increasing "psychologization" and "medicalization" of the difficulties of
      everyday life. 

PMID- 24284649
TI  - High-density distributed electrode network, a multi-functional electroporation
      method for delivery of molecules of different sizes.
AB  - We present a multi-functional electroporation method for delivery of biomolecule
      utilizing a high-density distributed electrode network (HDEN) under tri-phase
      electric stimulation. The HDEN device, with which drastic pH change during the
      electroporation was avoided,was demonstrated to be highly effective for
      transfection of not only DNA plasmids and small interfering RNAs (siRNA), but
      also a small molecular anti-cancer drug, into cells in adjustable volumes of cell
      suspension. The method constitutes a very flexible electroporation approach in a
      wide range of in vitro or ex vivo scenarios in various tubes, standard multi-well
      plates as well as flow chambers. 

PMID- 24284650
TI  - Geriatric consultation services for surgical patients.

PMID- 24284651
TI  - Numerical simulation of 3D boundary-driven acoustic streaming in microfluidic
      devices.
AB  - This article discusses three-dimensional (3D) boundary-driven streaming in
      acoustofluidic devices. Firstly, the 3D Rayleigh streaming pattern in a
      microchannel is simulated and its effect on the movement of microparticles of
      various sizes is demonstrated. The results obtained from this model show good
      comparisons with 3D experimental visualisations and demonstrate the fully 3D
      nature of the acoustic streaming field and the associated acoustophoretic motion
      of microparticles in acoustofluidic devices. This method is then applied to
      another acoustofluidic device in order to gain insights into an unusual in-plane
      streaming pattern. The origin of this streaming has not been fully described and
      its characteristics cannot be explained from the classical theory of Rayleigh
      streaming. The simulated in-plane streaming pattern was in good agreement with
      the experimental visualisation. The mechanism behind it is shown to be related to
      the active sound intensity field, which supports our previous findings on the
      mechanism of the in-plane acoustic streaming pattern visualised and modelled in a
      thin-layered capillary device. 

PMID- 24284652
TI  - Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis:
      A Systematic Review and Meta-analysis.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due
      to long duration of therapy and concurrent use of multiple second-line drugs,
      adverse drug events (ADEs) are regarded as the most important clinical
      consideration in patients undergoing anti-MDR-TB treatment. To evaluate the
      frequency and type of treatment-related ADEs owing to MDR-TB therapy. The
      Cochrane Library, MEDLINE, and EMBASE were searched from inception through
      October 1, 2012, with additional manual search of International Journal of
      Tuberculosis and Lung Disease. Studies with available ADEs were selected if MDR
      TB patients were treated with regimen including second-line drugs. Pooled
      estimations of incidence for each specific type of ADEs were calculated with 95%
      confidence intervals using random-effects model. Of the 5346 patients included,
      2602 (57.3%) experienced at least 1 kind of ADE. The 3 most common side effects
      were gastrointestinal disorders (32.1%), ototoxicity (14.6%), and psychiatric
      disorders (13.2%). Subgroup analyses based on each characteristic (study
      population, previous tuberculosis treated, human immunodeficiency virus
      prevalence, and length of treatment) did not show any significant difference
      between groups. Additionally, among 1519 patients who developed ADEs with
      available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB
      treatment. Adverse events were common among MDR-TB cases, occurring in more than
      half of the cases, with over two-thirds requiring change of anti-MDR-TB
      treatment. MDR-TB patients should be monitored closely and managed aggressively
      for side effects during therapy, especially for ototoxicity and psychiatric
      disorders. 

PMID- 24284653
TI  - Pulmonary drug toxicity: presentation of a case of recurrent diffuse alveolar
      damage caused by paroxetine.
AB  - Pulmonary drug toxicity is being diagnosed more often as a cause of acute and
      chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs
      have the potential to cause pulmonary toxicity. Recurrent diffuse alveolar damage
      is a rare manifestation of drug toxicity. We described an extremely rare case of
      recurrent diffuse alveolar damage caused by the antidepressant drug (paroxetine)
      resolved by a definitive suspension of the drug, after a recurrent respiratory
      failure because of inadvertently administering the drug. 

PMID- 24284654
TI  - Loss of ASAP3 destabilizes cytoskeletal protein ACTG1 to suppress cancer cell
      migration.
AB  - ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 (ASAP3), previously known
      as ACAP4, DDEFL1 and UPLC1, is considered to be an important regulator in cancer
      cell migration/invasion and actin-based cytoskeletal remodeling. However, the
      underlying mechanisms through which ASAP3 mediates these processes are not well
      elucidated. This study reported that in certain types of cancer cells, loss of
      ASAP3 suppressed cell migration/invasion, in part by destabilizing gamma-actin-1
      (ACTG1), a cytoskeletal protein considered to be an integral component of the
      cell migratory machinery, essential for the rearrangement of the dynamic
      cytoskeletal networks and important in diseases, such as brain malformation,
      hearing loss and cancer development. The data, for the first time, link ASAP3
      with ACTG1 in the regulation of cytoskeletal maintenance and cell motility.

PMID- 24284655
TI  - Graded synthetic approach for the fabrication of nanocrystal quantum dots for
      enhanced carrier injection in light-emitting diodes.
AB  - A synthetic approach for fabricating compositionally graded multishell
      nanocrystal quantum dots (NQDs) from cubic CdSe is presented. The structural
      shapes with each shell formation were examined using scanning transmission
      electron microscopy (STEM) coupled with energy dispersive x-ray spectroscopy and
      electron energy loss spectroscopy (EELS). The optical properties probed via time
      resolved spectroscopy further revealed detailed carrier behavior at the
      core/graded shell interface. A highly luminescing stable optical device was built
      using our graded multishell NQDs. 

PMID- 24284656
TI  - Nine-year trajectory of purchases of prescribed pain medications before and after
      in-patient interdisciplinary rehabilitation for chronic musculoskeletal
      disorders: a prospective, cohort, register-based study of 4,365 subjects.
AB  - OBJECTIVE: To investigate whether an interdisciplinary rehabilitation for chronic
      musculoskeletal disorders is associated with changes in the purchase of
      prescribed pain medication. DESIGN: Prospective register-based study. SUBJECTS:
      Employees in the public sector (n = 4,365) who participated in the rehabilitation
      programme between 1996 and 2009. METHODS: The changes in annual purchases of
      prescribed pain medication were measured for a 9-year exposure window, starting
      from 4 years before the start date of rehabilitation and ending 5 years after
      this date. RESULTS: Purchases of prescribed pain medication increased throughout
      the follow-up in all medication groups. The steepest increase was observed for
      analgesics, antidepressants, and hypnotics and sedatives. The growth rate of
      annual purchase, however, slowed significantly following the year of the start of
      rehabilitation for analgesics (annual growth rate (rate ratio) before and after
      rehabilitation 1.27 and 1.04, respectively, difference in trend p < 0.001);
      antidepressants (rate ratio 1.17 and 1.09, p = 0.005); and muscle relaxants (rate
      ratio 1.31 and 1.01, p < 0.001). For anxiolytics, and hypnotics and sedatives, no
      differences were observed in the trends of annual purchase before and after
      rehabilitation. CONCLUSION: Rehabilitation was associated with a slowing increase
      in purchases of prescribed pain medication amongst rehabilitants. This may be a
      reflection of the positive effect that rehabilitation has on the need for pain
      medication.

PMID- 24284657
TI  - Swedish strategies for health and safety in agriculture: a coordinated
      multiagency approach.
AB  - BACKGROUND: Occupational injuries are a major problem in agriculture world-wide.
      OBJECTIVE: Sweden is developing a national approach to scoordinate different
      stakeholders with the common goal of reducing injuries in the agricultural
      sector. METHOD: The Swedish strategy involves important factors, such as: 1)
      Collaboration between all stakeholders involved in health and safety in
      agriculture, 2) A national programme on injury prevention, 3) Coordination of
      actions and 4) Knowledge, attitude and behaviour in focus. PARTICIPANTS: This
      approach is being coordinated through the Swedish Committee on Working
      Environment (LAMK), a network acting to achieve a good, healthy and safe working
      environment in Swedish agriculture. The Committee consists of representatives of
      authorities, institutions, companies, research and education institutions and
      organisations working in the green sector. RESULTS: The Swedish model will be
      evaluated as a whole concept on its effect on the frequency of injuries in the
      agricultural industry in the beginning of 2014. Promising results has been shown
      in evaluations of minor parts. CONCLUSIONS: This coordinated approach has been
      applied in others countries (United States and New Zealand) as well and seems
      like an efficient way of using limited resources to achieve higher impact on a
      specific problems such as occupational injuries in agriculture.

PMID- 24284658
TI  - Normative median and ulnar nerve conduction values among a rural aged population.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is commonly diagnosed with a combination
      of characteristic symptoms and nerve conduction studies (NCS) across the wrist.
      Normative NCS values exist, but there is minimal data among older individuals or
      among rural populations. OBJECTIVE: To estimate distal median and ulnar sensory,
      and median motor latencies across the wrist in an older, rural population.
      METHODS: Hand symptom questionnaires and three standard NCS were obtained from
      1085 participants. Univariate and multiple linear regression analyses were
      conducted. RESULTS: Normative NCS values are presented from participants (mean
      age 57 years) who reported either no CTS symptoms or possible CTS symptoms.
      Covariates associated with NCS included age, hand temperature, body mass index,
      and height. CONCLUSIONS: This large normative NCS data set can be generalized to
      an older and rural population. Nerve conduction latencies were generally longer
      in this population than those reported in previous studies.

PMID- 24284659
TI  - Enabling positive work outcomes for people with low vision: two case studies.
AB  - This paper will focus on work-based environments, assistive technology solutions
      and compensatory strategies for people with low vision (that is, when vision
      cannot be satisfactorily corrected by spectacles/lenses). It presents two case
      studies to illustrate how functional capacity within a workplace can be maximized
      for individuals with vision impairment through a range of interventions. Each
      case study will demonstrate how the provision of a holistic suite of services
      delivered by a multidisciplinary team achieves positive and sustainable work
      outcomes for this cohort. One case study features an individual in a manual work
      role and the other in an office-based role. The following aspects of service
      delivery will be illustrated by each case study: Importance of comprehensive
      workplace and low vision assessment. Vocational planning. Compensatory strategies
      for job/task specific duties. Assistive technology and workplace modifications.
      Independent and safe travel skills to, from and within the workplace. Employer
      and co-worker training. 

PMID- 24284660
TI  - Ergonomic workplace evaluation and epidemiology of musculoskeletal discomfort on
      German dairy farms.
AB  - Previous European studies have shown a high prevalence of musculoskeletal
      discomfort (MSD) among milking parlor operatives, affecting at least 70% of the
      staff. The aim of the project was to find correlations between workplace design
      and prevalence of MSD. For this a data collection was carried out questioning the
      parlor operatives using a modified Nordic Questionnaire. On farm parlor specifics
      and bovimetrics of milked cows of a randomly-selected shift were measured. After
      that data was combined to compare the workplace design and the occurrence of MSD.
      The results showed that 94% of the female and 71% of the male workers suffered
      from MSD. The work place analysis revealed that women regularly worked above
      shoulder level and had to tort and bend more often than men because of the gender
      specific anthropometrics and the workplace design. The survey took into
      consideration that not only milking is considered strenuous but other farm tasks
      as well. The results also demonstrated that there is a need to take action to
      improve modern milking parlors. The existing helping devices are not sufficient
      to reduce the workload; reorganizing the work tasks, work schedule and the work
      place design is suggested.

PMID- 24284661
TI  - Forging partnerships between optometrists and ergonomists to improve visual
      comfort and productivity in the workplace.
AB  - Ergonomists and optometrists often have mutual clients/patients with complex
      visual needs in the workplace but communication between the professionals is
      usually indirect through the client/patient. This paper describes a joint
      professional development meeting between optometrists and ergonomists in
      Canberra, Australia, which included a discussion to explore how to improve
      communication between the two professions. Optometrists and ergonomists reported
      they would prefer more information before conducting assessments and providing
      advice. Vision screening forms commonly in use for computer workers were viewed
      as inadequate to meet these needs. Communication between the two professions was
      hampered by absence of contact details of the optometrist/ergonomist, perceptions
      that the other profession is too busy to talk, privacy considerations in sharing
      information and funding issues for shared care arrangements. There are
      opportunities for increasing awareness of good vision in workplaces.
      Communication between optometrists and ergonomists can be improved by developing
      information-sharing documents relevant to modern workplaces. 

PMID- 24284662
TI  - The visibility of controls and labels on electronic devices and their suitability
      for people with impaired vision.
AB  - BACKGROUND: People with low vision complain of difficulty operating controls on
      electronic appliances and equipment which suggests that the readability of
      controls and their labels is below their ability. OBJECTIVE: To investigate
      whether electronic appliances available today are designed with controls of
      sufficient size (at least 6/18 Snellen VA) and contrast (at least 30%) to
      facilitate identification and use by people with low vision. METHODS: Controls
      and labels of electronic appliances for sale in retail stores in Singapore
      (January, February 2012) and a sample of domestic appliances in Sydney, Australia
      (October, November of 2011) were evaluated in terms of high- and low- importance
      in function, size and contrast (luminance and colour difference). RESULTS: Labels
      and controls of 96 electronic appliances were evaluated. All controls were of
      sufficient size but 22% (26/117) of high- and 27% (12/44) of low-importance
      controls measured had insufficient luminance contrast. 79% (152/192) of high- and
      46% (24/52) of low-importance labels were of insufficient size. 17% (26/160) of
      the high- and 0.03% (1/33) of low-importance labels had insufficient luminance
      contrast. CONCLUSIONS: Most controls and labels of recently available electronic
      appliances can cause problems for operability in people with low vision.

PMID- 24284663
TI  - Ergonomics-related risk identification and pain analysis for farmers involved in
      rice field preparation.
AB  - BACKGROUND: A previous ergonomic screening of rice field preparation revealed
      farmer exposure to high risks of musculoskeletal disorders at the shoulders,
      hands, wrists and back. The screening method was not applied to muddy soil
      farming in which analysts could not observe farmer legs and feet. This study
      analyzed farmer pain in all stages of field preparation. OBJECTIVE: To examine
      the relationship of farmer experience and demographics to perceptions of pain and
      to identify body areas exposed to ergonomics risks, unknown to farmers. Results
      were expected to support interventions and guidelines for famers on physical
      behaviors towards minimizing risk of injury as well as validation of the
      screening approach. METHODS: Comparison of analyst screening results and farmer
      pain ratings using self-ratings and interviews. RESULTS: Farmer experience and
      age were significantly correlated with occurrence of pain and cramping. Less
      experienced farmers reported less pain in high-risk body parts (e.g., neck and
      lower back). More experienced farmers reported more pain in the legs, as compared
      with analyst risk ratings. CONCLUSIONS: Results demonstrated less experienced
      farmers to be unaware of critical areas of exposure to ergonomics risks.
      Correlation of farmer ratings of pain with analyst risk assessments support
      validity of the screening method for hazard identification and control.

PMID- 24284664
TI  - Farm tractors on Swedish public roads--age-related perspectives on police
      reported incidents and injuries.
AB  - BACKGROUND: Agriculture consistently ranks as one of the highest risk industries
      in North America and Europe. In addition to vehicle injuries and other injuries
      that occur on farms, farm vehicle drivers are also involved in collisions
      involving tractors and other slow-moving vehicles (SMVs) on public roads. These
      collisions often lead to injuries among farmers, family members, farm workers,
      and other road users. OBJECTIVE: To conduct a demographic analysis of road
      traffic incidents involving tractors in Sweden during the time period 1992-2009,
      with special consideration of how incidents vary with driver age. METHODS:
      Statistics from 2,305 police reports describing tractor-related road traffic
      incidents in Sweden in 1992-2009 were analysed with respect to driver age, type
      of incident, severity of injury, type of road user and other circumstances at the
      accident site. RESULTS: Tractors of all kinds were involved in 128 road traffic
      incidents annually, with 7 people killed, 44 seriously injured and 143 suffering
      minor injuries each year. The annual number of fatalities represented 1.2% of all
      Swedish road fatalities. Most road traffic incidents with farm tractors involved
      people aged 25-55 years (mean 45 years). However, most farm tractor drivers
      killed or injured belonged to younger or older age groups. Drivers aged 12-16
      years were over-represented in tractor incidents with no other vehicle involved.
      Older tractor drivers (> 55 years) were more often involved in incidents with
      passenger vehicles on entering traffic flows. The youngest tractor drivers aged
      12-16 years were more often involved in road traffic incidents during school
      holidays, and both youngest and oldest drivers (>65 years) during harvest time.
      CONCLUSIONS: Sweden has an ageing fleet of tractors, so increased attention to
      vehicle maintenance is needed to improve road safety. The over-representation of
      young children in tractor incidents suggests that it is questionable whether they
      should be allowed to operate farm vehicles. Farm vehicle drivers suffering the
      inevitable effects of ageing need increase their awareness of added risks. As
      road traffic incidents with tractors often involve private vehicles, creating
      awareness among the public of slow-moving farm vehicles is essential for
      improving overall road safety.

PMID- 24284665
TI  - Evolutionary adaptations: theoretical and practical implications for visual
      ergonomics.
AB  - BACKGROUND: The literature discussing visual ergonomics often mention that human
      vision is adapted to light emitted by the sun. However, theoretical and practical
      implications of this viewpoint is seldom discussed or taken into account.
      OBJECTIVE: The paper discusses some of the main theoretical implications of an
      evolutionary approach to visual ergonomics. DISCUSSION: Based on interactional
      theory and ideas from ecological psychology an evolutionary stress model is
      proposed as a theoretical framework for future research in ergonomics and human
      factors. The model stresses the importance of developing work environments that
      fits with our evolutionary adaptations. In accordance with evolutionary
      psychology, the environment of evolutionary adaptedness (EEA) and evolutionarily
      novel environments (EN) are used as key concepts. Using work with visual display
      units (VDU) as an example, the paper discusses how this knowledge can be utilized
      in an ergonomic analysis of risk factors in the work environment. CONCLUSION: The
      paper emphasises the importance of incorporating evolutionary theory in the field
      of ergonomics. Further, the paper encourages scientific practices that further
      our understanding of any phenomena beyond the borders of traditional proximal
      explanations.

PMID- 24284667
TI  - Setting visual pre-placement testing in a technology manufacturing environment.
AB  - Every day we use our eyes to perform activities of daily living and work. Aging
      changes as well as health conditions can impact an individual's visual function,
      making it more difficult to accurately perform work activities. Occupational
      therapists work closely with optometrists and employers to develop ways to
      accommodate for these changes so that the employee can continue to perform the
      work tasks. This manuscript outlines a case study of systematically developing
      visual demands analyses and pre-placement vision screening assessment protocols
      for individuals completing quality inspection positions. When the vision
      screening was completed, it was discovered that over 20% of the employees had
      visual deficits that were correctable. This screening process yielded improved
      quality results but also identification of previously undetected visual deficits.
      Further development of vision screening in the workplace is supported. 

PMID- 24284668
TI  - Reading from electronic devices versus hardcopy text.
AB  - BACKGROUND: The use of electronic reading devices has increased dramatically.
      However, some individuals report increased visual symptoms when reading from
      electronic screens. OBJECTIVE: This investigation compared reading from two
      electronic devices (Amazon Kindle or Apple Ipod) versus hardcopy text in two
      groups of 20 subjects. METHODS: Subjects performed a 20 min reading task for each
      condition. Both the accommodative response and reading rate were monitored during
      the trial. Immediately post-task, subjects completed a questionnaire concerning
      the ocular symptoms experienced during the task. RESULTS: In comparing the Kindle
      with hardcopy, no significant difference in the total symptom score was observed,
      although the mean score for the symptoms of tired eyes and eye discomfort was
      significantly higher with the Kindle. No significant differences in reading rate
      were found. When comparing the Ipod with hardcopy, no significant differences in
      symptom scores were found. The mean reading rate with the Ipod was significantly
      slower than for hardcopy while the mean lag of accommodation was significantly
      larger for the Ipod. CONCLUSIONS: Given the significant increase in symptoms with
      the Kindle, and larger lag of accommodation and reduced reading rate with the
      Ipod, one may conclude that reading from electronic devices is not equivalent to
      hardcopy.

PMID- 24284669
TI  - Neck pain brought into focus.
AB  - A time honored dictum states that the eyes "lead the body", i.e., that the body
      typically adjusts its position to compensate for an impoverished retinal image
      (e.g., as due to optical blur, and/or inappropriately sized visual target). But
      only moderate or low level of evidence exists in support of this view.
      Inconclusive evidence does not, however, equal negative evidence. The
      accommodation/vergence system does exhibit signs of overload in contemporary
      working life, including eye discomfort, transient myopia, altered pattern of eye
      lens oscillations, and associated phoria. Accommodation/vergence overload, caused
      by non-ergonomic near work, may also emerge as quickly as within one regular
      workday. Long-term musculoskeletal consequences of high accommodation/vergence
      demands have nevertheless not yet been studied in any detail. A research agenda
      which aims to provide multi-scientific evidence for eye-neck/shoulder
      interactions with public health implications and which also, in addition, study
      the eye-neck/shoulder mechanisms and elucidates the operating characteristics,
      should consequently be highly warranted. This new knowledge would be useful for
      physiotherapists, ergonomists and opticians, who in their profession treat
      patients experiencing vision- and musculoskeletal disorders. If both visual and
      the musculoskeletal aspects are given full and equal weight in the design and
      evaluation of work places, it is predicted to lead to an improved quality of life
      for the individual worker, and an enhanced productivity for the employer.

PMID- 24284670
TI  - Optimal correction in spectacles: intervention effects on eyestrain and
      musculoskeletal discomfort among postal workers.
AB  - BACKGROUND: The static posture of postal workers when sorting mail can lead to
      musculoskeletal discomfort. Research has shown a connection between eyestrain and
      upper-body musculoskeletal discomfort in general, including postal workers. A
      previous study of postal workers found that most of those with eye strain were in
      need of a new correction in their existing spectacles. OBJECTIVE: Evaluate
      intervention effects on eyestrain and musculoskeletal discomfort with new
      spectacles for postal workers. METHODS: Postal workers subjectively reported
      eyestrain, musculoskeletal discomfort and their opinions of the visual
      environment via questionnaires pre- and post-intervention. After an eye
      examination the postal workers were divided into two groups: those who needed new
      spectacles and those who did not. RESULTS: Those who needed new spectacles showed
      a higher prevalence of eyestrain and musculoskeletal discomfort pre-intervention.
      Post-intervention, the postal workers rated their vision better and the average
      eyestrain and musculoskeletal discomfort decreased for both groups. These workers
      also experienced a decrease in discomfort on the left (static) side of the neck
      while sorting mail. CONCLUSION: An intervention providing the optimal correction
      reduces eyestrain and decreases musculoskeletal discomfort, especially from the
      neck.

PMID- 24284671
TI  - Aging with a disability and state vocational rehabilitation services.
AB  - BACKGROUND: Disability prevalence in older adults is increasing. Given the low
      rates of employment among people with disabilities, especially those aging with
      multiple sclerosis (MS), spinal cord injury (SCI), late effects of polio (LEP),
      and muscular dystrophy (MD), services from federal-state vocational
      rehabilitation (VR) programs could positively impact employment status.
      OBJECTIVE: To describe VR services for individuals aging with MS, SCI, LEP and MD
      and the impact of aging on employment status. PARTICIPANTS: Thirteen Washington
      State VR counselors and 26 individuals, 45 to 65 years old, with MS, MD, LEP or
      SCI. METHODS: We examined national Rehabilitation Services Administration data
      (2006, 2007), including case closure, service outcomes and other demographics. We
      then purposively selected Washington State for our study. Interviews provided
      consumer and counselor perspectives on the components of successful case closure
      (employed) and the impact of aging and disability on employment. RESULTS:
      Washington State and national data were similar. Organizational and individual
      factors influence the effectiveness of VR services. CONCLUSION: People who could
      benefit from VR services are not being served; those who are served, are getting
      neither comprehensive services nor high quality outcomes. Additional research is
      needed to understand the variables associated with effective use of VR services.

PMID- 24284672
TI  - Work-based learning experiences help students with disabilities transition to
      careers: a case study of University of Washington projects.
AB  - This case study describes evidence-based practices employed by a collection of
      University of Washington projects that engage high school and postsecondary
      students with disabilities in work-based learning experiences such as industry
      and research internships, career development activities, job shadows, field
      trips, and mock interviews. The purpose of the article is two-fold. First,
      authors share best practices with others who wish to increase the participation
      of students with disabilities in work-based learning and thereby contribute to
      their academic and career success. The article discusses methods used to recruit
      students, employers and mentors, match students with specific opportunities, and
      prepare students for success. Second, authors share outcomes from studies
      regarding participation in these work-based learning opportunities, which include
      increased employment success, motivation to work toward a career, knowledge about
      careers and the workplace, job-related skills, ability to work with supervisors
      and coworkers, skills in self-advocating for accommodations, and perceived career
      options. 

PMID- 24284673
TI  - Preparing students with disabilities to transition from school to work through
      self-determination training.
AB  - BACKGROUND: It seems as if youth with disabilities are not graduation high school
      with the skills that they need to secure employment once they graduate.
      Particular, they are not graduating with self-determination skills. Instruction
      in self-determination skills enable youth to be leaders in their own lives and
      make decisions that will shape their future. This is especially true as they are
      transitioning from school to the workforce. Youth with disabilities must have a
      clear understanding of their abilities and be able to identify and request, and
      advocate for reasonable accommodations in the workplace. In addition, they must
      be prepared to negotiate how the accommodations are going to be presented within
      the work setting. OBJECTIVE: To present an overview of the literature that will
      demonstrate that self-determination skills are essential to youth with
      disabilities finding and securing employment. METHOD: An Eric and psycinfo
      Internet search was performed to gather articles and books concerning self
      determination. RESULTS: The results section includes a number of strategies that
      teachers and practitioners can use directly with their students and their
      clients. CONCLUSION: In conclusion, by incorporating self-determination skills
      training into the curriculum for transition-aged youth with disabilities they
      will be prepared to enter and succeed in the labor force.

PMID- 24284674
TI  - Risk factors, incidence and persistence of symptoms from the eyes among
      professional computer users.
AB  - BACKGROUND: Symptoms from the eyes are common among computer users. Knowledge is
      scarce about these problems, however. OBJECTIVES: The aim was to study risk
      factors, incidence and persistence of eye-symptoms among professionally active
      computer users. METHODS: This was a questionnaire based prospective study where
      1283 males and females from different professions and companies answered a
      baseline questionnaire about individual factors and working conditions, e.g.
      duration of daily computer work, comfort of screen work, psychosocial factors.
      Subjects were at baseline and 10 follow-ups asked about the number of days with
      eye-symptoms during the preceding month. RESULTS: The incidence-rate of symptoms
      persisting minimum three days was 0.38/person-year. A multivariate Hazard-ratio
      model showed significant associations with extended continuous computer work,
      tasks with high demands on eye-hand coordination, low level of control, visual
      discomfort, female sex and nicotine use. Eye-symptoms at baseline was a strong
      risk factor for new symptoms. CONCLUSION: The incidence of eye-symptoms among
      professional computer users is high and related to both individual and work
      related factors. The organization of computer work should secure frequent breaks
      from near-work at the computer screen. The severity of vision-related problems
      could in field studies be quantified by asking for the persistence of symptoms.

PMID- 24284675
TI  - Fighting fate: a seventy percent unemployment rate.
AB  - When children with disabilities imagine joining the adult world of work, the joys
      of choosing a future career path are marred by the high unemployment rates. As I
      maneuvered through the world of work as a young adult, my optimism remained
      slightly dampened by an acute awareness that 70% of blind Americans are
      unemployed. In my experience, the ultimate strategy for success in securing
      meaningful employment involved a combination of an honest assessment of one's
      skills and limits, and stubbornly searching for that niche position. 

PMID- 24284676
TI  - Employment, social capital, and community participation among Israelis with
      disabilities.
AB  - BACKGROUND: Employment, social capital, and community participation have emerged
      in recent years as significant concepts for realizing the human rights of
      individuals with disabilities. Yet the theoretical interrelationship of these
      concepts remains largely overlooked, as does the empirical basis for
      understanding the underlying connections. OBJECTIVES: This study explores the
      relationship between employment status, social capital, community participation,
      and well-being among Israelis with disabilities. It also explores the unique
      contribution of social capital to the well-being and integration of individuals
      with disabilities. METHOD: 274 participants with self-reported disabilities
      completed a questionnaire containing measures of individual social capital,
      community participation, well-being, and background data. Correlation and
      Univariate analysis were used to compare scores between employed (n=131) and non
      employed (n=143) participants, and logistic regression analysis was conducted to
      test the unique contribution of employment to social inclusion and well-being.
      RESULTS: Employed participants reported significantly higher levels of social
      capital and were more integrated in leisure and civic activities than their non
      employed counterparts. Moreover, employment status was found to have a
      significant contribution to the variance in the subjective well-being of
      participants. CONCLUSIONS: By more fully understanding the importance of social
      capital for community inclusion, practitioners can better address the importance
      of network-building during the rehabilitation process as a means of promoting
      social and vocational integration.

PMID- 24284677
TI  - Interviews with employed people with mobility impairments and limitations:
      environmental supports impacting work acquisition and satisfaction.
AB  - BACKGROUND: Less than 40% of people with disabilities work. Many studies have
      detailed the barriers to employment but few have examined the work experiences of
      those who are employed. OBJECTIVE: A description of work conditions valued by a
      specific segment of employed people with disabilities is provided. METHODS:
      Videotaped interviews of 33 successfully employed people with mobility
      impairments and limitations (PWMIL) were transcribed and analyzed to gather their
      perspectives on their work social and physical environments. RESULTS: Finding
      work was facilitated by family, friends and other social networks, vocational
      services, and prior education. Doing volunteer work, spending time at a paid and
      unpaid internship, and part-time work experiences were important aspects of job
      acquisition. Exterior and interior physical features were or had been made
      accessible. Expensive assistive technologies were paid for by the employee and
      their health insurance. Almost all personal assistance was provided by family,
      friends and co-workers. Work satisfaction included having a supportive employer,
      supportive co-workers, and flexible worksite policies. CONCLUSION: The interviews
      of employed PWMIL provide prospective employers and employees information on
      important social and physical work features that are needed to improve the
      possibilities for hiring people with disabilities and facilitating their
      successful careers.

PMID- 24284678
TI  - Developing inclusive employment: lessons from Telenor Open Mind.
AB  - BACKGROUND: Despite significant gains in legal rights for people with
      disabilities, the employment rate for individuals with disabilities in many
      countries remains extremely low. Programs to promote the inclusion of people with
      disabilities in the workforce can have an important impact on individuals'
      economic and social prospects, as well as societal benefits. OBJECTIVE: This
      article aims to explore Telenor Open Mind, a job training program at Norway's
      largest telecommunications company with financial support from Norway's Labor and
      Welfare Organization (NAV), which acts as a springboard for individuals with
      disabilities into the workplace. METHODS: A qualitative case study design was
      utilized to explore the Telenor Open Mind Program. Drawing on field research
      conducted in Oslo during 2011, this article explores subjective experiences of
      individuals involved with the program, through interviews and program
      observations. RESULTS: Telenor Open Mind's two-year program is comprised of a
      three month training period, in which individuals participate in computer and
      self-development courses followed by a 21-month paid internship where
      participants gain hands-on experience. The program has an average 75% rate of
      employment upon completion and a high rate of participant satisfaction.
      Participation in the program led to increased self-confidence and social
      development. The company experienced benefits from greater workplace satisfaction
      and reductions in sick leave rates. CONCLUSIONS: The Telenor Open Mind program
      has provided benefits for participants, the company, and society as a whole.
      Participants gain training, work experience, and increased employability. Telenor
      gains dedicated and trained employees, in addition to reducing sick leave
      absences among all employees. Finally, society benefits from the Open Mind
      program as the individuals who gain employment become tax-payers, and no longer
      need to receive benefits from the government.

PMID- 24284679
TI  - Employment outcomes among African Americans and Whites with mental illness.
AB  - BACKGROUND: People with mental illness often experience major difficulties in
      finding and maintaining sustainable employment. African Americans with mental
      illness have additional challenges to secure a job, as reflected in their
      significantly lower employment rates compared to Whites. OBJECTIVE: To examine
      the factors that contribute to racial disparities in employment outcomes for
      African-American and White Vocational Rehabilitation (VR) consumers with mental
      illness. METHODS: This study used VR data from a Midwestern state that included
      2,122 African American and 4,284 White participants who reported mental illness
      in their VR records. Logistic regression analyses were conducted. RESULTS:
      African Americans had significantly more closures after referral and were closed
      as non-rehabilitated more often than Whites. Logistic regressions indicated that
      African Americans are less likely to be employed compared to Whites. The
      regression also found differences by gender (females more likely to find jobs
      than males) and age (middle age consumers [36 to 50] were more likely to find
      jobs than younger consumers [18 to 35]). Case expenditures between $1,000 and
      $4,999 were significantly lower for African Americans. CONCLUSIONS: VR agencies
      need to remain vigilant of potential discrepancies in service delivery among
      consumers from various ethnic groups and work hard to assure as much equality as
      possible.

PMID- 24284680
TI  - Work environments of people with mobility impairments and limitations: Mobility
      Device User Work Survey (MWS).
AB  - BACKGROUND: Few studies of employed people who use wheelchairs, canes, crutches
      or walkers have been reported in the literature. One reason for this paucity of
      research reports is that surveys are most often made of unemployed individuals
      with disabilities a defined broadly. Understanding the work site of successfully
      employed people who use mobility devices requires the development of as survey
      that can be used to examine the important features of worksite from employees who
      use mobility devices at their worksites. OBJECTIVE: This article describes the
      development and psychometrics of a survey on currently employed people with lower
      limb impairments and mobility limitations who use mobility devices. The items in
      the Mobility Device User Work Survey (MWS) were based on interviews and survey
      items pilot tested on employed mobility device users. PARTICIPANTS: A sample of
      183 employed people who use mobility devices including wheelchairs, canes,
      crutches or walkers was recruited using internet postings on disability-related
      organizations. The average age of the sample was 46.3, most were college
      educated, 72% used wheelchairs and the average number of years of employment was
      24. METHODS: The MWS was completed by 183 people who met the inclusion criteria.
      The survey was sent to these same people a second time and 132 of them returned
      the second survey. RESULTS: The MWS consists of 106 questions on demographic,
      work and worksite characteristics and 58 subjective evaluation items that were
      organized into five scales. The internal consistencies (Cronbach's alpha) of the
      five scales were moderate (0.72) to good (0.93). Stability values of the five
      scales were calculated using correlations between forms and ranged from 0.70 to
      0.80. The evaluative scales were analyzed using exploratory factor analysis.
      CONCLUSIONS: The MWS provides a tool for studying the variables that influence
      employed people who use mobility devices. Future studies of unemployed people who
      use mobility devices may benefit from using the results of the MWS to plan
      interventions.

PMID- 24284681
TI  - Disability rights advocacy and employment: a qualitative study of the National
      Centre for the Employment of Disabled People (NCPEDP) in India.
AB  - In India, the low rate of employment of people with disabilities is a large
      problem in the growing economy. Looking at one advocacy group's strategies for
      influencing the private sector and lobbying the Indian government for more
      responsive employment policies, this article focuses on NCPEDP's holistic
      approach to increasing employment of people with disabilities as an example of
      notable, innovative practice. The article examines NCPEDP's strategies towards
      the private sector, public policy, and civil society, including its Disability
      Awards (highlighting inclusive workplaces), the 2001 and 2011 Census campaigns'
      efforts for people with disabilities to become accurately counted, and its
      networks of disability organizations that disseminate relevant information and
      campaign for greater equality across the nation. The benefits and limitations of
      these strategies are then assessed for lessons regarding the strategies available
      to small nongovernmental organizations seeking to influence employment, the
      private sector and public policy in other settings. 

PMID- 24284682
TI  - Are the treatment expectations of 'significant others' psychosocial obstacles to
      work participation for those with persistent low back pain?
AB  - BACKGROUND: Treatment expectations form a fundamental component of the self
      regulatory model of health behavior, which defines such cognitions as illness
      perceptions. Unrealistic and/or unhelpful treatment expectations have been linked
      to detrimental clinical and work outcomes in those with persistent low back pain.
      However, research of this nature has rarely focused on the influence of
      'significant others' (spouse/partner/close family member). OBJECTIVE: To provide
      an in-depth examination of the treatment expectations of the 'significant others'
      of individuals who have become unable to work due to persistent low back pain,
      highlighting how significant others may influence recovery and work participation
      outcomes for such individuals. PARTICIPANTS: A convenience sample (n=18) of work
      disability benefit claimants and their significant others were recruited from two
      settings in the North of England. METHOD: A qualitative research design was
      employed, and semi-structured interviews based on the chronic pain version of the
      Illness Perceptions Questionnaire-Revised were conducted with claimants and their
      significant others. Interview data were analysed using template analysis.
      RESULTS: It was found that significant others expected a substantial reduction or
      complete removal of pain in order for treatment to be considered successful. The
      pursuit of diagnostic tests was important in validating such expectations, and
      there was continued scepticism of treatments already undertaken or offered as an
      alternative. Like the individuals affected, significant others believed that a
      correct diagnosis had not yet been received, which led to a continued delay in
      return to work. CONCLUSIONS: This study demonstrates that significant others have
      similar unrealistic and/or unhelpful treatment expectations to those widely
      reported by individuals with persistent low back pain, and could further
      reinforce such illness perceptions and serve as wider psychosocial obstacles to
      recovery and continued work participation.

PMID- 24284683
TI  - Some life lessons in the work place: personal narrative/case study.
AB  - Michael Schwartz, a lawyer deaf since birth, describes his journey as a
      professional for the last 32 years since his graduation from NYU School of Law in
      1981. He offers a case study of his experiences with accommodations on the job as
      required by federal and state law. The study includes specific examples of what
      worked and what did not work for a deaf lawyer like him working at his craft.
      Schwartz wraps up with the lessons he learned over the last three decades as we
      moved from the model of non-compliance to that of compliance, even beyond
      compliance, with the mandates of law in the employment context. 

PMID- 24284684
TI  - Promoting school to work transition for students with emotional/behavioral
      disorders.
AB  - BACKGROUND: The successful transition of students from high school to adult
      occupations, including work and independent living, has been a major focus of the
      educational reform movement in the United States. However, despite good
      intentions, students with disabilities have less favorable transition outcomes
      than do students in the general population and employment opportunities are even
      less promising for students with emotional/behavioral disorders (EBD). OBJECTIVE:
      The purpose of this model demonstration project, funded by the US Department of
      Education, was to develop a program based on identified best practices to
      facilitate successful school to work transition for students with EBD.
      PARTICIPANTS: 47 students with EBD between the ages of 14 and 19 were
      participants in this project. The majority of participants in the project were
      white males with a generic diagnosis of a disruptive personality disorder.
      METHODS: Five cohort groups of students participated in a four phase program;
      Phase 1 - School-based Learning, Phase 2 - Community Involvement, Phase 3 - Paid,
      Supported Work Experience, and Phase 4 - Competitive Employment and Follow-Up.
      RESULTS: At the conclusion of the project, 30% of the project participants were
      competitively employed. Students had the most difficulty in Phase 3, but 81% of
      those who successfully completed Phase 3 obtained and retained competitive
      employment for a least one year. Four case studies are presented to illustrate
      findings. CONCLUSIONS: The School to Work Transition Program model shows promise
      for providing interventions to promote successful transition for students with
      EBD. Further research on the effectiveness of the overall model, as well as
      specific components of the model, is needed.

PMID- 24284685
TI  - Lifestyle and safety practices of firefighters and their relation to
      cardiovascular risk factors.
AB  - BACKGROUND: In the United States, over 50% of the deaths of on-duty firefighters
      are classified as sudden cardiac deaths. A holistic view of the multiple risk
      factors and their relation to the prevalence of cardiovascular disease (CVD) is
      necessary to determine a baseline for prevention. METHODS: This study surveyed
      154 firefighters in a large Midwestern county about their individual exposure to
      particulates, noise, heat stress, skin contamination, and physical stress;
      lifestyle factors such as exercise, diet, smoking, and alcohol consumption;
      health status; and demographic factors. RESULTS: Consumption of whole grains and
      alcohol were associated with a reduction of the risk of heart disease, while
      higher Body Mass Index (BMI) scores and increasing age were associated with
      increased risk of heart disease. CONCLUSIONS: Although firefighters are exposed
      to substantial occupational risks, only lifestyle factors were found to
      significantly predict CVD and related health issues. BMI is a modifiable risk
      factor, which, if controlled, could appreciably improve health outcomes.

PMID- 24284686
TI  - "If you can't do it now, you're out the door:" employees with traumatic brain
      injury - a case study.
AB  - This study considers the employment of persons with traumatic brain injury (TBI)
      from a disability-rights perspective. This approach calls for a shift from a
      focus on one's (in)capacity towards one's capability, incorporating both factors
      of impairment and of appropriate accommodation and supports to create inclusion.
      To give a voice to persons with TBI, the discussion is based on interviews with
      Tracey (pseudonym), a woman who incurred the injury at a young age and carried
      its implications as she entered the workforce. It illustrates the discrimination
      and prejudice encountered by such individuals in procuring employment and gaining
      acceptance in workplaces and the accommodation-related challenges. The case study
      discusses the complexities involved as a way for developing a better
      understanding what must be considered, from a disability-rights perspective,
      regarding employment and workplace of persons with TBI. The 2006 Convention on
      the Rights of Persons with Disabilities (CRPD) provides a legal reference for the
      discussion. 

PMID- 24284687
TI  - Access to digital library databases in higher education: design problems and
      infrastructural gaps.
AB  - BACKGROUND: After defining accessibility and usability, the author offers a broad
      survey of the research studies on digital content databases which have thus far
      primarily depended on data drawn from studies conducted by sighted researchers
      with non-disabled users employing screen readers and low vision devices.
      OBJECTIVE: This article aims at producing a detailed description of the
      difficulties confronted by blind screen reader users with online library
      databases which now hold most of the academic, peer-reviewed journal and
      periodical content essential for research and teaching in higher education.
      METHODS: The approach taken here is borrowed from descriptive ethnography which
      allows the author to create a complete picture of the accessibility and usability
      problems faced by an experienced academic user of digital library databases and
      screen readers. RESULTS: The author provides a detailed analysis of the different
      aspects of accessibility issues in digital databases under several headers with a
      special focus on full-text PDF files. CONCLUSIONS: The author emphasizes that
      long-term studies with actual, blind screen reader users employing both
      qualitative and computerized research tools can yield meaningful data for the
      designers and developers to improve these databases to a level that they begin to
      provide an equal access to the blind.

PMID- 24284688
TI  - Community based rehabilitation: Does it really improve the level of productivity
      among persons with physical disabilities?
AB  - BACKGROUND: The Community Based Rehabilitation (CBR) is a common approach to work
      with disable people to improve their quality of life by improving the level of
      productivity and integrating them into society. But the effectiveness of CBR
      varies by country to country. OBJECTIVE: The aim of the study was to find out
      whether CBR programs really improved the level of productivity among persons with
      physical disabilities. METHODS: A cross-sectional study was conducted among equal
      number of respondents (n=51) from each CBR coverage and non-coverage areas from
      two different upazilla (sub-districts) located 40 km away from the capital city
      of Bangladesh. Respondents were selected purposively and data were collected by
      face to face interviews. Willer's (1994) version of the Community Integration
      Questionnaire (CIQ) was used to measure the level of productivity among adult
      with physical disabilities. RESULTS: The mean score of total productivity
      integration in CBR coverage and non-coverage areas were 4.3 +/- 2.4 and 4.5 +/-
      2.2 respectively. This difference was statistically non-significant (p=0.602).The
      levels of productivity integration between CBR coverage and non-coverage areas
      varied only 2-4% (p=0.793). CONCLUSION: The mean score of productivity
      integration and levels of productivity were not different significantly in CBR
      coverage and non-coverage areas.

PMID- 24284689
TI  - The effect of an alternative keyboard on musculoskeletal discomfort: A randomized
      cross-over trial.
AB  - BACKGROUND: There is limited research on the effectiveness of alternative
      keyboards in reducing discomfort in the workplace. OBJECTIVE: We hypothesized
      that participants using a fixed split-angle (alternative) keyboard would report
      significantly greater improvements in discomfort in comparison to those using a
      standard keyboard. Additionally, we hypothesized that at 5 months participants
      would significantly prefer the configuration of the alternative keyboard in
      comparison to the standard keyboard. METHOD: In this randomized cross-over trial
      77 symptomatic computer operators used fixed split-angle or standard flat
      keyboards for five months in their workplace, then switched to the other
      keyboard. Discomfort was collected weekly using the Weekly Discomfort Survey and
      usability was measured monthly. RESULTS: There was no significant keyboard by
      period effect on any discomfort measure. The number of participants with
      discomfort decreased dramatically in the first month of use, regardless of
      keyboard type, and this number remained relatively unchanged for the remainder of
      the study. Participants' ratings significantly favored the standard flat keyboard
      for usability. CONCLUSIONS: This study does not support the use of fixed split
      angle keyboards over standard flat keyboards to reduce discomfort in the
      workplace. Further research is needed to evaluate if subgroups of keyboard users
      might benefit.

PMID- 24284690
TI  - Homecoming of soldiers who are citizens: Re-employment and financial status of
      returning Army National Guard soldiers from Operations Iraqi Freedom (OIF) and
      Enduring Freedom (OEF).
AB  - This study examined civilian employment among Army National Guard soldiers who
      had recently returned from Operations Iraqi Freedom (OIF) and Enduring Freedom
      (OEF). Of specific interest were relationships of re-employment and financial
      difficulties to several conditions, such as amount of social support during and
      after deployment, combat exposure, negative feelings during and after deployment,
      and postdeployment adjustment symptoms. Survey data from the Army's Reintegration
      Unit Risk Inventory were used (4,546 soldiers in 50 units who were deployed
      during 2010). Few soldiers reported financial difficulties during deployment
      (7.1% of the sample) and after having returned (11.8%). Of those who reported
      postdeployment financial difficulties, nearly one-half had reported such
      difficulties during deployment, and not having resumed the predeployment job was
      associated with more postdeployment financial difficulties. Logistic regression
      analyses showed the relative contribution of the study variables to changed
      financial status, from deployment to postdeployment. Reported deployment support
      (e.g., trust in the unit chain-of-command and available support) was associated
      with decreased financial difficulties. In contrast, increased financial
      difficulties were associated with having seen others wounded or killed in combat.
      Other postdeployment experiences, such as feelings of anger and frustration and
      available support, were associated with increased financial difficulties, in
      addition to alcohol use, trouble sleeping and suicidal thoughts. Implications of
      results for policy and practice to lessen financial hardships and job loss
      associated with deployment are discussed. 

PMID- 24284691
TI  - Work environment perceptions following relocation to open-plan offices: A twelve
      month longitudinal study.
AB  - BACKGROUND: A workplace's design can have various positive or negative effects on
      the employees and since the 1970s the advantages and disadvantages of open-plan
      offices have been discussed. OBJECTIVE: The aim of this study was to investigate
      perceived health, work environment and self-estimated productivity one month
      before and at three, six and twelve months after relocation from individual
      offices to an open-plan office environment. METHODS: Employees from three
      departments within the same company group and who worked with relatively similar
      tasks and who were planned to be relocated from private offices to open-plan
      offices were invited to participate. Questionnaires comprising items from The
      Salutogenic Health Indicator Scale, The Work Experience Measurement Scale, the
      questionnaire by Brennan et al. about perceived performance and one question from
      the Work Ability Index were sent to participants one month before relocation
      (baseline) to open-plan offices and then at three, six and twelve months after
      relocation. At baseline, 82 questionnaires were sent out. The response rate was
      85%. At the follow-ups 77-79 questionnaires were sent out and the response-rate
      was 70%-81%. RESULTS: At follow-ups, perceived health, job satisfaction and
      performance had generally deteriorated. CONCLUSIONS: The results of the study
      indicate that employees' perception of health, work environment and performance
      decreased during a 12 month period following relocation from individual offices
      to open-plan offices.

PMID- 24284692
TI  - The effect of glare on eye movements when reading.
AB  - BACKGROUND: Glare is a very common source of image degradation when performing
      computer work. Since reading is a task that is very sensitive to image
      degradation induced disability glare affects reading performance. OBJECTIVE: To
      assess the effect of different glare conditions on eye movements when reading on
      a computer screen. Glare conditions have an impact on reading. This observation
      is based on the results from a study where we investigated how reading eye
      movements were affected by glare. PARTICIPANTS: Sixteen subjects with normal
      vision participated in this study. METHOD: In a balanced repeated-measurement
      study, all subjects performed equal near-vision reading tasks. In addition to the
      condition of no glare three controlled conditions of glare were used: direct
      light, indirect light, and desk luminary. The subjects read three texts under
      each condition: First a short standardized text (IReST), secondly a longer
      newspaper text, and finally an additional IReST text. The texts were read on a
      Tobii T120 eye tracker. RESULTS: The results show that glare does have a negative
      effect on reading performance. The more adverse the lighting condition was, the
      slower the reading speed became. The decrease was primarily a result of increased
      fixation durations. Both glare conditions of direct and indirect glare increased
      the fixation durations significantly (p < 0.05). CONCLUSION: This study shows
      that even moderate glare conditions can have an impact on reading. The results
      show that it is important to follow recommendations of lighting design in
      computer work environment in order to avoid disability glare.

PMID- 24284693
TI  - Manual patient transfers used most often by student and staff nurses are
      consistent with their perceptions of transfer training, and performance
      confidence.
AB  - BACKGROUND: A disconnect in manual patient transfer (MPT) training practices for
      nurses, between what is taught and used in academic and clinical settings, could
      have implications for injury. OBJECTIVE: This study aimed to determine: 1. what
      MPTs student and staff nurses use in clinical settings, and 2. if the MPTs used
      most often were also the ones they perceived that they received training for and
      had the most confidence performing. METHODS: Survey responses from student nurses
      (n=163) (mid-sized university) and staff nurses (n=33) (local hospital) regarding
      19 MPTs were analyzed to determine which transfers were perceived to be used most
      often, and which ones they had received training for and had the greatest
      confidence performing. RESULTS: The MPTs nurses perceived using most often were
      the same transfers they had the greatest confidence performing and for which they
      perceived receiving training. However, these MPTs were not taught at the
      university at the time of this investigation. CONCLUSION: Reducing the disconnect
      between manual patient transfer training obtained in the academic and clinical
      environments will hopefully reduce the risk of injury for nurses and improve the
      quality of care for patients.

PMID- 24284694
TI  - Hospital nurses working wounded: motivations and obstacles to return to work as
      experienced by nurses with injuries.
AB  - BACKGROUND: Despite the high rate of work-related injuries among hospital nurses,
      there is limited understanding of factors that serve to motivate or hinder nurses
      return to work following injury. OBJECTIVES: Perspectives of nurses with work
      related injuries, as they relate to obstacles and motivations to return to work,
      consequences of injury, and influences of work climate were documented. METHODS:
      This was a sub-study of nurses taken from a larger investigation of hospital
      workers. A purposive sample of 16 nurses was interviewed. Analysis was carried
      out using grounded theory as the research method. RESULTS: Nurses' responses fell
      into four concepts: organizational influences, personal conditions, costs and
      losses, and employee health as influenced by workers' compensation systems.
      Conceptualization of these concepts resulted in key categories: injury as an
      expected consequence of hospital work; nursing alone versus nursing together; the
      impact of injury on professional, family, and social roles; and nurses'
      understanding of and involvement with the workers' compensation system.
      DISCUSSION: The findings provide new perspective into features that support or
      hinder nurses' with injuries return to work and corroborate existing occupational
      health research. Consideration of these findings by hospital and employee health
      managers may help promote more effective return to work programs within the
      hospital setting.

PMID- 24284695
TI  - Factors associated with inadequate work ability among women in the clothing
      industry.
AB  - BACKGROUND: Work ability depends on a balance between individual resources and
      work demands. OBJECTIVE: This study evaluated factors that are associated with
      inadequate work ability among workers in the clothing industry. METHOD: We
      conducted a cross-sectional observational study of 306 workers in 40 small and
      medium-sized enterprises. We assessed work ability, individual resources,
      physical and psychosocial demands, and aspects of life outside work using a
      binary logistic regression model with hierarchical data entry. RESULTS: The mean
      work ability was 42.5 (SD=3.5); when adjusted for age, only 11% of the workers
      showed inadequate work ability. The final model revealed that smoking, high
      isometric physical load, and poor physical environmental conditions were the most
      significant predictors of inadequate work ability. CONCLUSIONS: Good working
      conditions and worker education must be implemented to eliminate factors that can
      be changed and that have a negative impact on work ability. These initiatives
      include anti-smoking measures, improved postures at work, and better physical
      environmental conditions.

PMID- 24284696
TI  - Football fever could be a dose of dengue.

PMID- 24284708
TI  - China aims for the Moon.

PMID- 24284709
TI  - LHC plans for open data future.

PMID- 24284710
TI  - Project ranks billions of drug interactions.

PMID- 24284711
TI  - China battles army of invaders.

PMID- 24284712
TI  - Nations fight back on ivory.

PMID- 24284713
TI  - Research ethics: 3 ways to blow the whistle.

PMID- 24284714
TI  - Immunology: The pursuit of happiness.

PMID- 24284719
TI  - Russian universities need change of tack.

PMID- 24284720
TI  - Mitigate damage risk from bush fires.

PMID- 24284721
TI  - TB vaccine failure was predictable.

PMID- 24284722
TI  - Definition of maths genius is elusive.

PMID- 24284723
TI  - Greece's high CT scanning record.

PMID- 24284724
TI  - George Herbig (1920-2013).

PMID- 24284725
TI  - Astrophysics: Exception tests the rules.

PMID- 24284726
TI  - Molecular biology: Antibiotic re-frames decoding.

PMID- 24284727
TI  - Puzzling accretion onto a black hole in the ultraluminous X-ray source M 101 ULX
      1.
AB  - There are two proposed explanations for ultraluminous X-ray sources (ULXs) with
      luminosities in excess of 10(39) erg s(-1). They could be intermediate-mass black
      holes (more than 100-1,000 solar masses, M sun symbol) radiating at sub-maximal
      (sub-Eddington) rates, as in Galactic black-hole X-ray binaries but with larger,
      cooler accretion disks. Alternatively, they could be stellar-mass black holes
      radiating at Eddington or super-Eddington rates. On its discovery, M 101 ULX-1
      had a luminosity of 3 * 10(39) erg s(-1) and a supersoft thermal disk spectrum
      with an exceptionally low temperature--uncomplicated by photons energized by a
      corona of hot electrons--more consistent with the expected appearance of an
      accreting intermediate-mass black hole. Here we report optical spectroscopic
      monitoring of M 101 ULX-1. We confirm the previous suggestion that the system
      contains a Wolf-Rayet star, and reveal that the orbital period is 8.2 days. The
      black hole has a minimum mass of 5 M sun symbol, and more probably a mass of 20 M
      sun symbol-30 M sun symbol, but we argue that it is very unlikely to be an
      intermediate-mass black hole. Therefore, its exceptionally soft spectra at high
      Eddington ratios violate the expectations for accretion onto stellar-mass black
      holes. Accretion must occur from captured stellar wind, which has hitherto been
      thought to be so inefficient that it could not power an ultraluminous source.

PMID- 24284729
TI  - Does quadrupole stability imply LLSVP fixity?

PMID- 24284730
TI  - Conrad et al. reply.

PMID- 24284731
TI  - EFM data mapped into 2D images of tip-sample contact potential difference and
      capacitance second derivative.
AB  - We report a simple technique for mapping Electrostatic Force Microscopy (EFM)
      bias sweep data into 2D images. The method allows simultaneous probing, in the
      same scanning area, of the contact potential difference and the second derivative
      of the capacitance between tip and sample, along with the height information. The
      only required equipment consists of a microscope with lift-mode EFM capable of
      phase shift detection. We designate this approach as Scanning Probe Potential
      Electrostatic Force Microscopy (SPP-EFM). An open-source MATLAB Graphical User
      Interface (GUI) for images acquisition, processing and analysis has been
      developed. The technique is tested with Indium Tin Oxide (ITO) and with poly(3
      hexylthiophene) (P3HT) nanowires for organic transistor applications. 

PMID- 24284733
TI  - Does histology predict outcome for malignant vascular tumors of the liver?
AB  - BACKGROUND AND OBJECTIVES: Malignant vascular tumors (MVT) of the liver are
      uncommon and poorly understood. We hypothesized that tumor histology is a
      predominant factor associated with survival in these tumors. METHODS: Patients
      with malignant histopathologic diagnoses of hepatic angiosarcoma (AS),
      hemangioendothelioma (HE) and its epithelioid variant (EHE), or
      hemangiopericytoma (HP) were identified using the SEER database (1973-2007).
      Overall survival (OS) was studied with Kaplan-Meier curves. RESULTS: We included
      297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated
      metastatic potential, although EHE and AS had the highest rate of regional or
      distant metastases (75% each). Patients with AS had the shortest median OS (1
      month), however, those undergoing surgery had improved survival (6 months). Three
      patients with AS underwent liver transplant and lived for 11, 21, and 91 months
      each. Patients with EHE had the longest overall median survival of 75 months (30
      183, P < 0.001). Surgical resection and transplant did not demonstrate an
      improvement in OS of patients with EHE in multivariable models. CONCLUSIONS:
      Histology is an important factor in determining survival for patients with
      hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have
      shorter survival but may benefit from surgery.

PMID- 24284734
TI  - Sarcomatoid carcinoma in head and neck: a review of 30 years of experience-
      clinical outcomes and reconstructive results.
AB  - PROBLEM PRESENTED: Sarcomatoid carcinoma (SaCa) is a rare variant of squamous
      cell carcinoma (SCC) with sarcomatoid features. This study investigated the
      clinical presentation and outcomes of head and neck SaCa. In addition,
      reconstructive outcome for a subset of patients was also evaluated. STUDIES
      UNDERTAKEN: Seventy-eight SaCa cases including 72 men and 6 women were identified
      from 13,777 head and neck SCC cases. Clinical outcomes were evaluated based on
      locoregional control, distant metastases, and multivariate analyses.
      Reconstructive outcome was evaluated by flap survival rate. RESULT: Of the 78
      cases, 71% (55) of cases were located in the oral mucosa; 64% (50) of patients
      were classified as T3 or T4 at the time of diagnosis. The 5-year survival was
      only 16%. Multivariate analysis revealed better outcomes only when the patient
      had a history of previous SCC. Forty-five patients underwent flap reconstruction,
      with 98% flap survival rate but the functional result varied because of the
      inevitable adjuvant radiotherapy and advanced stage of tumor. CONCLUSIONS:
      Sarcomatoid carcinoma is a different entity from the conventional SCC of the head
      and neck. Sarcomatoid carcinoma carries a poorer prognosis despite aggressive
      surgical intervention and concurrent adjuvant therapies. It remains a great
      challenge for clinical oncologists, and the optimal treatment strategy requires
      further studies. Free flap is still preferred for defect reconstruction but the
      design should be simplified to avoid complications.

PMID- 24284732
TI  - In vivo optical signatures of neuronal death in a mouse model of Alzheimer's
      disease.
AB  - BACKGROUND: There currently is a need for cost-effective, quantitative techniques
      to evaluate the gradual progression of Alzheimer's disease (AD). Measurement
      techniques based on diffuse optical spectroscopy can detect blood perfusion and
      brain cellular composition changes, through measuring the absorption (ua ) and
      reduced scattering (us ') coefficients, respectively, using non-ionizing near
      infrared light. Previous work has shown that brain perfusion deficits in an AD
      mouse model can be detected. The objective of this study was to determine if us '
      is sensitive to the inflammation and neuron death found in AD. METHODS: We used
      spatial frequency domain imaging (SFDI) to form quantitative maps of ua and us '
      in 3-month old male CaM/Tet-DTA mice harboring transgenes for the doxycyline
      regulated neuronal expression of diphtheria toxin. When doxycycline is removed
      from the diet, CaM/Tet-DTA mice develop progressive neuronal loss in forebrain
      neurons. Mice (n = 5) were imaged longitudinally immediately prior to and after
      23 days of lesion induction, and ua and us ' (30 wavelengths, 650-970 nm) were
      compared to properties obtained from Tet-DTA controls (n = 5). Neuron death and
      infiltration of inflammatory cells in brain cortical slices was confirmed with
      immunohistochemistry. RESULTS: No significant difference in baseline scattering
      and absorption were measured between CaM/Tet-DTA mice and controls. After 23 days
      of lesion induction, brain cortical us ' was 11-16% higher in the CaM/Tet-DTA
      mice than in controls (P < 0.03). Longitudinal imaging showed no significant
      difference in us ' between the first and 23rd day of imaging in controls.
      Removing doxycycline from the diet was associated with a significant decrease in
      total hemoglobin concentrations (119 +/- 9 uM vs. 91 +/- 8 uM) (P < 0.05) in
      controls, but not in CaM/Tet-DTA mice. CONCLUSIONS: Neuronal death and brain
      inflammation are associated with increased tissue scattering (us ') and this
      optical biomarker may be useful in pre-clinical AD therapy evaluation or
      monitoring of disease progression in AD patients.

PMID- 24284735
TI  - Tailoring folded-fasciocutaneous flap for the restoration of oral commissure
      morphology.
AB  - The reconstruction of a through-and-through cheek defect with oral commissure
      involvement can be challenging. When attempting to reconstruct its seam-like
      structure or to replace its supple lip tissue, postoperative morbidities such as
      drooling, microstomia, and poor aesthetic appearance can often occur and be
      difficult to correct. After inspecting the oral commissure, one can observe that
      the morphology of the upper lip acts as a "drape" hanging over the upper teeth,
      whereas the lower lip functions similarly to a "dam" holding the constant pour of
      saliva within the oral cavity. We noted that if we tailored a single
      fasciocutaneous flap to satisfy these morphologies during reconstruction, not
      only were the mentioned morbidities of reconstruction greatly diminished, but the
      reconstructed oral commissure could also spontaneously mimic the contralateral
      side in form. We presented 10 consecutive patients with cheek defects with
      concomitant oral commissure involvement, which underwent reconstruction by using
      a single-folded fasciocutaneous flap. We described how the flaps are tailored to
      suit the mentioned upper and lower lip morphology. For certain defects, such as a
      cheek defect with oral commissure involvement, the loss of functional morphology
      greatly outweighs its anatomical or tissue losses. Our method provides a simple
      and straightforward surgical option in this area, which was previously perceived
      as a challenging reconstruction site. 

PMID- 24284736
TI  - Infraeyebrow blepharoplasty incorporated browpexy in an Asian population.
AB  - BACKGROUND: In Taiwan, upper blepharoplasty has become one of the most commonly
      performed rejuvenation operations. Many surgeons have modified their approaches
      to managing the aging changes of the upper eyelids. We elucidate our experiences
      of applying infraeyebrow blepharoplasty incorporated with browpexy and periosteum
      scoring, including its indications, operative procedures, and postoperative
      changes after the surgery in our research. METHODS: Eighty lids in 40 patients
      were subjected to this surgery from January 2010 to January 2012. All patients
      had upper eyelid dermatochalasis with visual field limitation, and the functions
      of their levator palpabrae were all normal. The primary indications of the
      procedure were upper lid dermatochalasis with lateral hooding. These 40 patients
      underwent infraeyebrow blepharoplasty incorporated with browpexy at Taipei
      Veteran General Hospital. RESULTS: The average patient age was 59.5 years (36-73
      years). The average resection width was 12.3 mm (8-15 mm). The mean operative
      time was 50 minutes. The mean height of brow descending at the midpupil line was
      2.4 mm (0-4 mm). The mean height of lateral brow descending was 2.74 mm (-0.6 to
      5.4 mm). The lateral brow was higher than the middle brow with a mean height of
      2.64 mm (0-4.2 mm). All patients were satisfied with the results. No complication
      related to sensory abnormalities and visible scars was observed. CONCLUSIONS: Our
      modified method with infraeyebrow blepharoplasty incorporated with browpexy not
      only keeps the advantages, which have been mentioned in previous literature, but
      also keeps the lateral brow in an ideal position and avoids the flattening of the
      brow.

PMID- 24284737
TI  - A successful free fibula transfer in the patient with chronic peroneal vein
      thrombosis.
AB  - Despite the rare incidence, occult chronic thrombosis of peroneal veins of the
      fibula graft during the flap harvest presents a challenge to produce a successful
      reconstruction. In this article, we present a case of a 54-year-old man with
      chronic thrombosis of peroneal veins found during the harvest of the free fibula
      osteocutaneous flap for reconstruction of the mandible defect after tumor
      ablation. With near-total obliteration of the lumens, a small lumen with residual
      blood outflow was identified under microscopic magnification. A successful flap
      transfer was made possible by using the recanalized lumen around the chronic
      thrombus of the vein for microanastomosis. The pathological analysis of the vein
      revealed that the recanalized lumens and the endothelial cells-specific CD31
      immunohistochemical stain highlighted the endothelium of regenerative lumen
      around the chronic thrombus. The abundant deposition of thick collagen fibers
      also suggested a chronic nature of the thrombus. However, although a successful
      microsurgical free osteocutaneous flap transfer might be possible in the patient
      with lower-limb chronic peroneal vein thrombosis, a careful preoperative
      evaluation with imaging study is recommended for high-risk patients. 

PMID- 24284738
TI  - The role of frontalis orbicularis oculi muscle flap for correction of
      blepharoptosis with poor levator function.
AB  - On the basis of the close anatomical interdigitation between the longitudinal
      oriented frontalis muscle and the horizontal-oriented orbicularis oculi muscle
      (OOM), frontalis OOM (FOOM) flap was developed to treat blepharoptosis.
      Retrospective study during an 11-year period, 66 patients with 81 poor levator
      function ptotic eyelids accepted FOOM flap shortening (65 lids; 80.2%) or double
      breasted FOOM flap advancement (16 lids; 19.8%) to correct blepharoptosis. There
      were 51 (77.3%) patients with unilateral ptosis and 15 (22.7%) patients with
      bilateral ptosis. Severity of blepharoptosis included severe type in 72 (88.9%)
      lids, moderate type in 5 (6.2%) lids, and mild type in 4 (4.9%) lids. The
      underlying etiology included congenital origin in 43 (65.1%) patients,
      involutional change in 19 (28.8%) patients, and neurologic origin in 4 (6.1%)
      patients. Marginal reflex distance 1 and lid slit distance improved from -1.6
      (2.0) to 3.3 (1.2) and 3.2 (2.0) to 7.2 (1.4) mm, respectively, after operation.
      The postoperative outcome includes good results in 54 (81.8%) patients, fair
      results in 10 (15.2%) patients, and poor results in 2 (3.0%) patients. The
      undercorrection or recurrence rate is 14.8%, and secondary revision rate is
      11.1%. Positive Hering law is 17.6% among patients with unilateral ptosis.
      Overall patients' satisfaction rate is 95.1%. Both FOOM flap shortening and
      double-breasted FOOM flap advancement are effective to treat poor levator
      function blepharoptosis. Double-breasted FOOM flap advancement is highly
      recommended because of the more natural contour and minimal lagophthalmos
      postoperatively, because of the maximal preservation of OOM.

PMID- 24284739
TI  - Management of extremity neurilemmomas: clinical series and literature review.
AB  - BACKGROUND: Delicate enucleation of neurilemmoma preserves most of nerve
      fascicles and causes minimal nerve function impairment. Accurate preoperative
      diagnosis of neurilemmoma is based on clinical findings and image studies.
      MATERIALS AND METHODS: Between November 2003 and February 2013, operations for
      the treatment of neurilemmoma were performed on 14 patients (12 men and 2 women)
      at our institution. The image studies in this series were collected. The tumor
      mass was approached by splitting the epineurium. In a few cases, enucleation of
      the neurilemmoma caused some fascicles loss, but reconstruction with sural nerve
      grafts preserved nerve function. RESULTS: Before surgery, 7 patients received
      computed tomographic scan, 4 patients underwent magnetic resonance imaging, and 3
      patients received sonography. Six patients presented with motor or sensory
      deficits immediately after tumor enucleation. Three patients recovered completely
      from the neurological defects with or without nerve reconstruction. CONCLUSIONS:
      Our results indicate that neurilemmoma can be removed by delicate enucleation
      with an acceptable risk of injury to the nerve trunk.

PMID- 24284740
TI  - A comparison between proximal lateral leg flap and radial forearm flap for
      intraoral reconstruction.
AB  - Free flaps have become a popular option for the reconstruction of intraoral
      defects. The radial forearm flap used to be the workhorse flap for small and thin
      defects, but was associated with numerous donor-site morbidities. The proximal
      lateral leg flap can provide a thin and pliable tissue similar to the radial
      forearm flap but without the related donor-site morbidities. We compared the
      differences between these 2 flaps. Thirty-four patients with intraoral defects
      from September 2005 to October 2011 were reconstructed, using the radial forearm
      flap in 23 cases, and the proximal lateral leg flap in 11 cases. The radial
      forearm flap group had a success rate of 95.6%. The flap survival rate was 100%
      in the proximal lateral leg flap group. However, the difference was statistically
      insignificant. Skin graft was required in 22 of the 23 cases for the donor site
      of the radial forearm flap. Partial loss of the skin graft occurred in 5/22 (23%)
      of the patients, with exposure of tendons in 3/22 (14%). Delay in healing of the
      donor sites occurred in 6/23 (26%) of the patients. The donor sites of the
      proximal lateral leg flap were all closed primarily. One case developed wound
      dehiscence and this healed by conservative treatment. Long-term follow-up showed
      functional impairment of the donor forearm (reduced extension or grip strength)
      in 17% of the patients. Thirty percent of the patients developed sensory
      disturbance and 48% complained of poor outcome of the donor forearms. In the
      proximal lateral leg flap group, no motor or sensory functional deficits were
      seen. No patients complained of poor outcome of the donor legs. Primary closure
      of the donor site of the proximal lateral leg flap could be performed if the flap
      width was less than 6 cm. This flap is useful for patients with small and thin
      intraoral defects and is associated with minimal donor-site morbidity when
      compared to the radial forearm flap. 

PMID- 24284741
TI  - The lower trapezius musculocutaneous flap for head and neck reconstruction: two
      decades of clinical experience.
AB  - BACKGROUND: Microsurgical free flap has gained the popularity over pedicle flap
      nowadays in the reconstruction of head and neck. However, pedicled flaps remain a
      promising alternative and have a remarkable position in selected patients. This
      review study aimed to determine the reliability and versatility of the lower
      trapezius musculocutaneous flap for reconstructing complex defects in the head
      and neck. METHODS: Between 1993 and 2012, 22 male and 10 female patients
      underwent a total of 32 lower trapezius flap reconstructions for complex defects
      that included neoplasm extirpation (n = 21), radionecrosis (n = 6), dehisced
      laminectomy (n = 2), pressure sore (n = 2), and necrotizing fasciitis (n = 1).
      The most common site of defect was the perioral region, followed by the neck,
      posterior skull, back, temporal region, shoulder, and the upper arm. Flap design
      was based on the defect size and location, as well as the ability to close the
      donor site primarily and to preserve muscle function. Outcome has been evaluated
      by the hospital course, postoperative morbidity, mortality, resultant cosmetics,
      and function at donor and recipient sites. RESULTS: Stable wound coverage with
      total flap survival was achieved in 30 (93.75%) patients, 2 patients had partial
      flap necrosis which required flap reinsertion and skin graft coverage. All donor
      sites were closed primarily. Seroma developed in 2 (6.25%) patients, which were
      solved by needle aspiration. All muscle function was preserved. Eight patients
      died of their primary disease. CONCLUSIONS: For selected patients who have
      advanced stage cancer, surgical sequelae after free flap surgery, unable to
      tolerate microsurgery, or special defect location, pedicled lower trapezius
      musculocutaneous flap provides efficient and effective reconstruction for complex
      defects especially in the head and neck.

PMID- 24284742
TI  - Surgical site infections among high-risk patients in clean-contaminated head and
      neck reconstructive surgery: concordance with preoperative oral flora.
AB  - BACKGROUND: Salivary contamination of surgical wounds in clean-contaminated head
      and neck surgery with free flap reconstruction remains a major cause of infection
      and leads to significant morbidity. This study investigates the correlation
      between intraoral flora and surgical site infections (SSIs) among high-risk head
      and neck cancer patients undergoing resection and free flap reconstruction.
      METHODS: One hundred twenty-nine patients were identified as being at high risk
      for infective complications based on cancer stage, tumor size, comorbid factors,
      and extent of reconstruction. All patients had intraoral swab cultures before
      surgery. Patients with culture-confirmed SSI after surgery were chosen for
      analysis, using the kappa index and its 95% confidence interval for concordance
      analysis. All patients received clindamycin and gentamicin for antibiotic
      prophylaxis for 5 days. Antibiotic susceptibility testing of all isolates was
      obtained and analyzed. RESULTS: Thirty-seven patients experienced SSI, or an
      infection rate of 28.3%, occurring at a mean of 9.3 postoperative days. The
      overall concordance between oral flora and SSI was fair to moderate (kappa index
      of 0.25), but detailed analysis shows a higher concordance for known and
      opportunistic pathogens, such as Pseudomonas aeruginosa and Enterococcus
      faecalis, compared to typical oral commensals. Antibiotic susceptibility tests
      show rapid and significant increases in resistance to clindamycin, indicating a
      need for a more effective alternative. CONCLUSIONS: Predicting pathogens in SSI
      using preoperative oral swabs did not demonstrate a good concordance in general
      for patients undergoing clean-contaminated head and neck surgery, although
      concordance for certain pathogenic species seem to be higher than for typical
      intraoral commensals. The rapid development of resistance to clindamycin
      precludes its use as a prophylactic agent.

PMID- 24284743
TI  - Functional and radiologic outcome of open reduction and internal fixation of
      condylar head and neck fractures using miniplate or microplate system.
AB  - BACKGROUND: Although the appropriate management of condylar process fractures
      after miniplate or microplate fixation has been described, there has been no
      comparative analysis of these plating systems. METHODS: A retrospective review of
      patients who underwent open reduction and internal fixation (ORIF) of condylar
      head or neck fractures at our institution from January 2000 through August 2010
      identified 70 patients. Of these, 38 were treated with microplates and 32 with
      miniplates. The primary functional and radiographic results were the maximal
      mouth opening and condylar bone resorption, respectively. The rates of
      complications, including malocclusion, chin deviation, temporomandibular joint
      complaints, and facial nerve palsy, were recorded. RESULTS: The maximal mouth
      opening was larger in the microplate group than in the miniplate group throughout
      the follow-up period; this difference was statistically significant 12 (P =
      0.020), 18 (P = 0.026), and 24 (P = 0.032) months after ORIF. Similarly, the
      radiographic scores for bone resorption and condyle morphology were significantly
      better in the microplate group than in the miniplate group throughout the follow
      up period [6 (P = 0.011), 12 (P = 0.035), 24 (P = 0.026), and 48 (P = 0.040)
      months after ORIF]. Moreover, patients who underwent miniplate fixation
      experienced a significantly higher incidence of temporomandibular joint click
      than those who underwent microplate fixation (P = 0.014). CONCLUSIONS:
      Microplates limit dissection, providing excellent fixation for intracapsular
      condylar head fractures, and also provide adequate rigidity for fixation of
      condylar neck fractures. Microplate fixation of condylar head and neck fractures
      yielded excellent functional and radiographic results. The rates of complications
      after microplate fixation were equal to or less than those in the miniplate
      group. Prospective studies are needed to confirm these findings.

PMID- 24284744
TI  - The effects of microenvironment on wound healing by keratinocytes derived from
      mesenchymal stem cells.
AB  - Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into
      various cell types, including keratinocyte-like cells, within suitable
      microniches. In this study, we aimed to investigate the effects of culture media,
      cell coculture, and a tissue-engineering biocomposite on the differentiation of
      mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a
      surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were
      transfected using pCX-EGFP expressing green fluorescence, were used to track MESC
      derived keratinocytes. Weak expression of the keratinocyte early marker
      Cytokeratin 14 (CK-14) was observed up to 12 days when MESCs were cultured in a
      keratinocyte culture medium on tissue culture plastic and on a
      gelatin/collagen/polycaprolactone (GCP) biocomposite. MESCs cocultured with human
      keratinocyte cells (HKCs) also expressed CK-14, but did not express CK-14 when
      cocultured with human fibroblast cells (HFCs). Furthermore, CK-14 expression was
      observed when MESCs were cocultured by seeding HKCs or HFCs on the same or
      opposite side of the GCP biocomposite. The highest CK-14 expression was observed
      by seeding MESCs and HKCs on the same side of the GCP composite and with HFCs on
      the opposite side. To verify the effectiveness of wound healing in vivo, adipose
      derived stem cells were applied to treat surgical wounds in nude mice. An obvious
      epidermis multilayer and better collagen deposition during wound healing were
      observed, as assessed by Masson staining. This study demonstrated the potential
      of keratinocyte-like differentiation from mesenchymal stem cells for use in
      promoting wound closure and skin regeneration.

PMID- 24284745
TI  - Using adenovirus armed short hairpin RNA targeting transforming growth factor
      beta1 inhibits melanoma growth and metastasis in an ex vivo animal model.
AB  - The transforming growth factor beta (TGF-beta) is the key molecule implicated in
      impaired immune function in human patients with malignant melanoma. TGF-beta can
      promote tumor growth, invasion, and metastasis in advanced stages of melanoma.
      Blocking these tumor-promoting effects of TGF-beta provides a potentially
      important therapeutic strategy for the treatment of melanoma. In this study, we
      used an adenovirus-based shRNA expression system and successfully constructed
      Ad/TGF-beta1-RNA interference (RNAi) which mediated the RNAi for TGF-beta1 gene
      silencing. We examined the effects of TGF-beta1 protein knockdown by RNAi on the
      growth and metastasis of melanoma in C57BL/6 mice induced by the B16F0 cell line.
      The TGF-beta1 hairpin oligonucleotide was cloned into adenoviral vector. The
      resulting recombinant adenoviruses infected murine melanoma cell line, B16F0, and
      designated as B16F0/TGF-beta1-RNAi cells. The blank adenoviral vector also
      infected B16F0 cells and designed as B16F0/vector-control cells served as a
      control. TGF-beta1 expression was reduced in B16F0/TGF-beta1-RNAi cells compared
      with B16F0 cells and B16F0/vector-control cells. Three million wild-type B16F0
      cells, B16F0/vector-control cells, and B16F0/TGF-beta1-RNAi cells were injected
      subcutaneously into the right flanks of adult female syngeneic mice C57BL/6. The
      tumor sizes were 756.09 (65.35), 798.48 (78.77), and 203.55 (24.56) mm at the
      14th day in the mice receiving B16F0 cells, B16F0/vector-control cells, and
      B16F0/TGFbeta1-RNAi cells, respectively. The P value was less than 0.01 by 1-way
      analysis of variance. TGF-beta1 knockdown in B16F0 cells enhanced the
      infiltration of CD4 and CD8 T cells in the tumor regions. C57BL/6 mice were
      evaluated for pulmonary metastasis after tail vein injection of 2 million B16F0
      cells, B16F0/vector-control cells, and B16F0/TGF-beta1-RNAi cells. The pulmonary
      metastasis also reduced significantly on days 14 day and 21 in mice injected with
      B16F0/TGF-beta1-RNAi tumors. The blood vessel density of the tumors markedly
      reduced in B16F0/TGF-beta1-RNAi tumors. Our results showed that Ad/TGF-beta1-RNAi
      could induce silencing of the TGF-beta1 gene effectively. Silencing of TGF-beta1
      expression in B16F0 cells by RNAi technology can inhibit the growth and
      metastasis of this tumor after being transplanted to C57BL/6 mice. This kind of
      adenoviral vector based on RNAi might be a promising vector for cancer therapy.

PMID- 24284746
TI  - Management of malocclusion and facial asymmetry secondary to fractures of the
      mandibular condyle process.
AB  - INTRODUCTION: Most condylar process fractures can be managed conservatively with
      satisfactory outcome. However, unsuccessful treatment can result in malocclusion
      and facial asymmetry. We report our experience in surgical management of
      malunited condylar process fractures. METHODS: This is a retrospective review of
      clinical records, photographs, imaging, and dental models of 12 consecutive
      patients who presented with malocclusion and facial asymmetry after nonoperative
      or failed treatment of condylar process fractures. Eight patients who presented
      relatively early (<6 months) after the initial trauma were treated with
      subcondylar osteotomy (SCO), whereas 4 patients who presented relatively late
      (>18 months) were treated with sagittal split osteotomy (SSO). These 2 groups
      were compared in terms of 3 parameters, namely, maximum mouth opening, aesthetic
      improvement, and patient satisfaction. RESULTS: The 2 groups were statistically
      similar in all 3 parameters, with the SCO group trending toward higher scores in
      all 3 parameters. The mean increase in maximal mouth opening in the SCO group was
      21 versus 2.5 mm in the SSO group. CONCLUSIONS: Subcondylar osteotomy, performed
      at a relatively early time point, is at least as effective, if not more
      effective, than traditional SSO in the treatment of subcondylar malunions. Given
      this finding, a lower threshold should be adopted for the primary treatment of
      acute subcondylar fractures with open reduction and internal fixation, especially
      those with moderate displacement that may be at high risk for malunion.

PMID- 24284748
TI  - Effect of ergonomics training on agreement between expert and nonexpert ratings
      of the potential for musculoskeletal harm in manufacturing tasks.
AB  - OBJECTIVE: To evaluate the effect of ergonomics training on non-ergonomists'
      ability to recognize and characterize the potential for musculoskeletal harm in
      manufacturing tasks. METHODS: Ergonomics training was delivered to members of a
      participatory ergonomics team in a manufacturing facility. Before and after
      training, participatory ergonomics team members and the research team rated the
      potential for musculoskeletal harm for each of 30 tasks. Measures of agreement
      included Pearson, concordance, and intraclass correlation coefficients. RESULTS:
      Measures of agreement generally improved after training. The greatest agreement
      was observed for ratings of the potential for musculoskeletal harm to the low
      back. The greatest improvement in agreement was observed for ratings of the
      potential for musculoskeletal harm to the neck/shoulder. CONCLUSIONS: The
      training seemed to improve non-experts' ability to identify the potential for
      musculoskeletal harm.

PMID- 24284747
TI  - Integrated worker health protection and promotion programs: overview and
      perspectives on health and economic outcomes.
AB  - OBJECTIVE: To describe integrated worker health protection and promotion (IWHPP)
      program characteristics, to discuss the rationale for the integration of
      occupational safety and health and worksite health promotion programs, and to
      summarize what is known about the impact of these programs on health and economic
      outcomes. METHODS: A descriptive assessment of the current state of the IWHPP
      field and a review of studies on the effectiveness of IWHPP programs on health
      and economic outcomes were undertaken. RESULTS: Sufficient evidence of
      effectiveness was found for IWHPP programs when health outcomes were considered.
      Impact on productivity-related outcomes is considered promising, but
      inconclusive, whereas insufficient evidence was found for health care
      expenditures. CONCLUSIONS: Existing evidence supports an integrated approach in
      terms of health outcomes but will benefit significantly from research designed to
      support the business case for employers of various company sizes and industry
      types.

PMID- 24284749
TI  - From worker health to citizen health: moving upstream.
AB  - New rapid growth economies, urbanization, health systems crises, and "big data"
      are causing fundamental changes in social structures and systems, including
      health. These forces for change have significant consequences for occupational
      and environmental medicine and will challenge the specialty to think beyond
      workers and workplaces as the principal locus of innovation for health and
      performance. These trends are placing great emphasis on upstream strategies for
      addressing the complex systems dynamics of the social determinants of health. The
      need to engage systems in communities for healthier workforces is a shift in
      orientation from worker and workplace centric to citizen and community centric.
      This change for occupational and environmental medicine requires extending
      systems approaches in the workplace to communities that are systems of systems
      and that require different skills, data, tools, and partnerships. 

PMID- 24284750
TI  - Value of social media in reaching and engaging employers in Total Worker Health.
AB  - OBJECTIVE: To describe the initial use of social media by the National Institute
      for Occupational Safety and Health (NIOSH) Total Worker HealthTM (TWH) Program
      and the University of Iowa Healthier Workforce Center for Excellence (HWCE)
      Outreach Program. METHODS: Social media analytics tools and process evaluation
      methods were used to derive initial insights on the social media strategies used
      by the NIOSH and the HWCE. RESULTS: The on-line community size for the NIOSH TWH
      Program indicated 100% growth in 6 months; however, social media platforms have
      been slow to gain participation among employers. CONCLUSION: The NIOSH TWH
      Program and the HWCE Outreach Program have found social media tools as an
      effective way to expand reach, foster engagement, and gain understanding of
      audience interests around TWH concepts. More needs to be known about how to best
      use social media to reach and engage target audiences on issues relevant to TWH.

PMID- 24284751
TI  - Characterizing the needs of a young working population: making the case for total
      worker health in an emerging workforce.
AB  - OBJECTIVE: Young workers are at increased risk for occupational injuries. Many
      lack appropriate skills to avoid workplace hazards. In addition, existing safety
      programs neither address total worker health principles nor align with the
      relatively high technological expectations of young workers. This article aimed
      to identify the content and process for an on-line total worker health training
      for young workers. METHODS: During the summer of 2012, an on-line survey (n =
      187) assessed young workers' behavior, knowledge, and attitudes on total worker
      health topics and on-line training delivery methods. RESULTS: Forty-five percent
      of the workers indicated this was their first job; new workers demonstrated lower
      safety knowledge scores than returning workers. In addition, results demonstrated
      that workers would benefit from health behavior interventions delivered through
      technology-based means. CONCLUSIONS: Findings characterize the work-related needs
      for this population and demonstrate the utility of using on-line training.

PMID- 24284752
TI  - The NIOSH Total Worker HealthTM program: an overview.
AB  - OBJECTIVE: The objective of this article was to provide an overview of the
      National Institute for Occupational Safety and Health (NIOSH) Total Worker
      HealthTM (TWHTM) Program that was launched by the institute in 2011. METHODS:
      This article describes the TWHTM concept, relevant issues, and the NIOSH Program.
      Examples of the concept are provided. RESULTS: Total Worker HealthTM is a
      strategy integrating occupational safety and health protection with health
      promotion to prevent worker injury and illness and to advance health and well
      being. CONCLUSIONS: The NIOSH TWHTM Program responds to demands for information
      and practical solutions to the health, safety, and well-being challenges that
      workers and their employers face. It also addresses issues related to the
      nation's need to sustain a globally competitive workforce.

PMID- 24284753
TI  - Examining national trends in worker health with the National Health Interview
      Survey.
AB  - OBJECTIVE: To describe data from the National Health Interview Survey (NHIS),
      both the annual core survey and periodic occupational health supplements (OHSs),
      available for examining national trends in worker health. METHODS: The NHIS is an
      annual in-person household survey with a cross-sectional multistage clustered
      sample design to produce nationally representative health data. The 2010 NHIS
      included an OHS. RESULTS: Prevalence rates of various health conditions and
      health behaviors among workers based on multiple years of NHIS core data are
      available. In addition, the 2010 NHIS-OHS data provide prevalence rates of
      selected health conditions, work organization factors, and occupational exposures
      among US workers by industry and occupation. CONCLUSIONS: The publicly available
      NHIS data can be used to identify areas of concern for various industries and for
      benchmarking data from specific worker groups against national averages.

PMID- 24284754
TI  - Participatory ergonomics as a model for integrated programs to prevent chronic
      disease.
AB  - OBJECTIVE: To describe the value of participatory methods for achieving
      successful workplace health promotion (WHP) programming, and specifically the
      relevance of participatory ergonomics (PE) for the Total Worker Health (TWH)
      initiative. METHODS: We review the concept of macroergonomics, and how PE is
      embedded within that framework, and its utility to modern WHP approaches such as
      "social health promotion." We illustrate these constructs in practice within TWH.
      RESULTS AND CONCLUSIONS: Participatory ergonomics is relevant to WHP because (1)
      psychosocial stress contributes to individual health behaviors as well as chronic
      diseases; (2) job stress cannot be addressed without employee involvement in
      hazard identification and solutions; (3) the interaction of multiple levels
      within an organization requires attention to needs and constraints at all levels,
      just as the social-ecological model addresses higher-level determinants of and
      constraints on individual behaviors.

PMID- 24284755
TI  - Integrated health programs, health outcomes, and return on investment: measuring
      workplace health promotion and integrated program effectiveness.
AB  - OBJECTIVE: To explore return on investment (ROI) in workplace health promotion
      studies. METHODS: Studies with high ROI attribution for workplace health
      promotion were reanalyzed using standardized measures. Key variables included
      intervention duration, sector and population size, annualized cost, and health
      outcomes. RESULTS: ROI was often overestimated. Programs with the highest
      reported ROI were concentrated in large corporations, where cognitive programs
      incurred low per person costs. Ten of the 12 studies involved individualized
      health promotion only, and did not engage work organizational modification or
      integration with occupational health. Some effective health interventions were
      discounted because they were not easily monetized. CONCLUSIONS: ROI, an
      investment metric, amplifies short-term labor-related effects and discounts
      longer-term chronic disease prevention.

PMID- 24284756
TI  - Physical activity at work contributes little to patient care workers' weekly
      totals.
AB  - OBJECTIVE: To determine the number of minutes of moderate and vigorous physical
      activity at work in comparison to weekly total minutes in a pilot study of 50
      hospital patient care workers. METHODS: Workers wore accelerometers during work
      and nonwork hours for 7 days, and completed surveys at the end of the seventh
      day. RESULTS: Although the participants reported on average 206 minutes of
      moderate activity at work, the accelerometers recorded on average 30 minutes of
      moderate activity at work. For the 7 days the accelerometers measured a total of
      165 minutes of moderate activity. Self-reported fatigue and functional
      limitations were negatively correlated albeit weakly with measured minutes of
      vigorous activity outside of work. CONCLUSIONS: Physical activity at work on
      patient care units contributes a small fraction to these workers' weekly totals,
      and in turn meeting guidelines.

PMID- 24284757
TI  - An employee total health management-based survey of Iowa employers.
AB  - OBJECTIVE: To implement an Employee Total Health Management (ETHM) model-based
      questionnaire and provide estimates of model program elements among a statewide
      sample of Iowa employers. METHODS: Survey a stratified random sample of Iowa
      employers, and characterize and estimate employer participation in ETHM program
      elements. RESULTS: Iowa employers are implementing less than 30% of all 12
      components of ETHM, with the exception of occupational safety and health (46.6%)
      and workers' compensation insurance coverage (89.2%), but intend modest expansion
      of all components in the coming year. CONCLUSIONS: The ETHM questionnaire-based
      survey provides estimates of progress Iowa employers are making toward
      implementing components of Total Worker Health programs.

PMID- 24284758
TI  - 2012 Total Worker HealthTM symposium.

PMID- 24284759
TI  - Total worker health and work-life stress.
AB  - OBJECTIVE: Review relationships between work-life stress and health behaviors to
      advance understanding of pathways between occupational and individual risk
      factors and health and safety outcomes. METHODS: A background on the Total Worker
      Health concept is provided, and a review of research on the relationship between
      work-life stress and health behaviors is presented. RESULTS: Research evidence
      indicates that work-life stress serves as a negative occupational exposure
      relating to poor health behaviors, including smoking, poor food choices, low
      levels of exercise, and even decreased sleep time. CONCLUSION: The association
      between work-life stress and adverse health behaviors suggests that interventions
      at both the occupational (health protection) and individual (health promotion)
      level may be helpful in mitigating effects of work-life stress, consistent with
      the Total Worker Health approach. Further study is needed to investigate gains
      from an integrated prevention strategy.

PMID- 24284760
TI  - Employer Health and Productivity RoadmapTM strategy.
AB  - The National Institute for Occupational Safety and Health Total Worker HealthTM
      Program defines essential elements of an integrated health protection and health
      promotion model to improve the health, safety, and performance of employers and
      employees. The lack of a clear strategy to address the core drivers of poor
      health, excessive medical costs, and lost productivity has deterred a
      comprehensive, integrated, and proactive approach to meet these challenges. The
      Employer Health and Productivity RoadmapTM, comprising six interrelated and
      integrated core elements, creates a framework of shared accountability for both
      employers and their health and productivity partners to implement and monitor
      actionable measures that improve health, maximize productivity, and reduce
      excessive costs. The strategy is most effective when linked to a financially
      incentivized health management program or consumer-directed health plan insurance
      benefit design. 

PMID- 24284761
TI  - The Intervention Design and Analysis Scorecard: a planning tool for participatory
      design of integrated health and safety interventions in the workplace.
AB  - OBJECTIVE: As part of a Research-to-Practice Toolkit development effort by the
      Center for the Promotion of Health in the New England Workplace, to develop and
      test a structured participatory approach for engaging front-line employees in the
      design of integrated health protection and promotion interventions. METHODS: On
      the basis of a participatory ergonomics framework, the Intervention Design and
      Analysis Scorecard (IDEAS) provides a stepwise approach for developing
      intervention proposals, including root cause analysis and setting evaluation
      criteria such as scope, obstacles, and cost/benefit trade-offs. The IDEAS was
      tested at four diverse worksites with trained facilitators. RESULTS: Employees
      were able to develop and gain management support for integrated interventions at
      each worksite. CONCLUSIONS: The IDEAS can be used effectively by front-line
      employees to plan integrated interventions in a program dedicated to continuous
      improvement of employee health protection/promotion and Total Worker Health.

PMID- 24284762
TI  - Integration of health protection and health promotion: rationale, indicators, and
      metrics.
AB  - OBJECTIVE: To offer a definition of an "integrated" approach to worker health and
      operationalize this definition using indicators of the extent to which integrated
      efforts are implemented in an organization. METHODS: Guided by the question-How
      will we know it when we see it?-we reviewed relevant literature to identify
      available definitions and metrics, and used a modified Delphi process to review
      and refine indicators and measures of integrated approaches. RESULTS: A
      definition of integrated approaches to worker health is proposed and accompanied
      by indicators and measures that may be used by researchers, employers, and
      workers. CONCLUSIONS: A shared understanding of what is meant by integrated
      approaches to protect and promote worker health has the potential to improve
      dialogue among researchers and facilitate the research-to-practice process.

PMID- 24284765
TI  - Application of collocated GPS and seismic sensors to earthquake monitoring and
      early warning.
AB  - We explore the use of collocated GPS and seismic sensors for earthquake
      monitoring and early warning. The GPS and seismic data collected during the 2011
      Tohoku-Oki (Japan) and the 2010 El Mayor-Cucapah (Mexico) earthquakes are
      analyzed by using a tightly-coupled integration. The performance of the
      integrated results is validated by both time and frequency domain analysis. We
      detect the P-wave arrival and observe small-scale features of the movement from
      the integrated results and locate the epicenter. Meanwhile, permanent offsets are
      extracted from the integrated displacements highly accurately and used for
      reliable fault slip inversion and magnitude estimation. 

PMID- 24284764
TI  - A 94-GHz millimeter-wave sensor for speech signal acquisition.
AB  - High frequency millimeter-wave (MMW) radar-like sensors enable the detection of
      speech signals. This novel non-acoustic speech detection method has some special
      advantages not offered by traditional microphones, such as preventing strong
      acoustic interference, high directional sensitivity with penetration, and long
      detection distance. A 94-GHz MMW radar sensor was employed in this study to test
      its speech acquisition ability. A 34-GHz zero intermediate frequency radar, a 34
      GHz superheterodyne radar, and a microphone were also used for comparison
      purposes. A short-time phase-spectrum-compensation algorithm was used to enhance
      the detected speech. The results reveal that the 94-GHz radar sensor showed the
      highest sensitivity and obtained the highest speech quality subjective
      measurement score. This result suggests that the MMW radar sensor has better
      performance than a traditional microphone in terms of speech detection for
      detection distances longer than 1 m. As a substitute for the traditional speech
      acquisition method, this novel speech acquisition method demonstrates a large
      potential for many speech related applications. 

PMID- 24284763
TI  - Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation
      during in vitro culture.
AB  - Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but
      the vast majority of their progeny loses stemness during culture. In this study,
      we compared DNA-methylation (DNAm) profiles of freshly isolated and culture
      expanded HPCs. Culture conditions of CD34(+) cells - either with or without
      mesenchymal stromal cells (MSCs) - had relatively little impact on DNAm, although
      proliferation is greatly increased by stromal support. However, all cultured HPCs
      - even those which remained CD34(+) - acquired significant DNA-hypermethylation.
      DNA-hypermethylation occurred particularly in up-stream promoter regions, shore
      regions of CpG islands, binding sites for PU.1, HOXA5 and RUNX1, and it was
      reflected in differential gene expression and variant transcripts of DNMT3A. Low
      concentrations of DNAm inhibitors slightly increased the frequency of colony
      forming unit initiating cells. Our results demonstrate that HPCs acquire DNA
      hypermethylation at specific sites in the genome which is relevant for the rapid
      loss of stemness during in vitro manipulation. 

PMID- 24284766
TI  - Offset printing plate quality sensor on a low-cost processor.
AB  - The aim of this work is to develop a microprocessor-based sensor that measures
      the quality of the offset printing plate through the introduction of different
      image analysis applications. The main features of the presented system are the
      low cost, the low amount of power consumption, its modularity and easy
      integration with other industrial modules for printing plates, and its robustness
      against noise environments. For the sake of clarity, a viability analysis of
      previous software is presented through different strategies, based on dynamic
      histogram and Hough transform. This paper provides performance and scalability
      data compared with existing costly commercial devices. Furthermore, a general
      overview of quality control possibilities for printing plates is presented and
      could be useful to a system where such controls are regularly conducted. 

PMID- 24284767
TI  - An energy efficient stable election-based routing algorithm for wireless sensor
      networks.
AB  - Sensor nodes usually have limited energy supply and they are impractical to
      recharge. How to balance traffic load in sensors in order to increase network
      lifetime is a very challenging research issue. Many clustering algorithms have
      been proposed recently for wireless sensor networks (WSNs). However, sensor
      networks with one fixed sink node often suffer from a hot spots problem since
      nodes near sinks have more traffic burden to forward during a multi-hop
      transmission process. The use of mobile sinks has been shown to be an effective
      technique to enhance network performance features such as latency, energy
      efficiency, network lifetime, etc. In this paper, a modified Stable Election
      Protocol (SEP), which employs a mobile sink, has been proposed for WSNs with non
      uniform node distribution. The decision of selecting cluster heads by the sink is
      based on the minimization of the associated additional energy and residual energy
      at each node. Besides, the cluster head selects the shortest path to reach the
      sink between the direct approach and the indirect approach with the use of the
      nearest cluster head. Simulation results demonstrate that our algorithm has
      better performance than traditional routing algorithms, such as LEACH and SEP. 

PMID- 24284768
TI  - Field monitoring of column shortenings in a high-rise building during
      construction.
AB  - The automatic monitoring of shortenings of vertical members in high-rise
      buildings under construction is a challenging issue in the high-rise building
      construction field. In this study, a practical system for monitoring column
      shortening in a high-rise building under construction is presented. The proposed
      monitoring system comprises the following components: (1) a wireless sensing
      system and (2) the corresponding monitoring software. The wireless sensing system
      comprises the sensors and energy-efficient wireless sensing units (sensor nodes,
      master nodes, and repeater nodes), which automate the processes for measuring the
      strains of vertical members and transmitting the measured data to the remote
      server. The monitoring software enables construction administrators to monitor
      real-time data collected by the server via an Internet connection. The proposed
      monitoring system is applied to actual 66-floor and 72-floor high-rise buildings
      under construction. The system enables automatic and real-time measurements of
      the shortening of vertical members, which can result in more precise
      construction. 

PMID- 24284769
TI  - Robust finger vein ROI localization based on flexible segmentation.
AB  - Finger veins have been proved to be an effective biometric for personal
      identification in the recent years. However, finger vein images are easily
      affected by influences such as image translation, orientation, scale, scattering,
      finger structure, complicated background, uneven illumination, and collection
      posture. All these factors may contribute to inaccurate region of interest (ROI)
      definition, and so degrade the performance of finger vein identification system.
      To improve this problem, in this paper, we propose a finger vein ROI localization
      method that has high effectiveness and robustness against the above factors. The
      proposed method consists of a set of steps to localize ROIs accurately, namely
      segmentation, orientation correction, and ROI detection. Accurate finger region
      segmentation and correct calculated orientation can support each other to produce
      higher accuracy in localizing ROIs. Extensive experiments have been performed on
      the finger vein image database, MMCBNU_6000, to verify the robustness of the
      proposed method. The proposed method shows the segmentation accuracy of 100%.
      Furthermore, the average processing time of the proposed method is 22 ms for an
      acquired image, which satisfies the criterion of a real-time finger vein
      identification system. 

PMID- 24284770
TI  - Alignment of the measurement scale mark during immersion hydrometer calibration
      using an image processing system.
AB  - The present work presents an improved method to align the measurement scale mark
      in an immersion hydrometer calibration system of CENAM, the National Metrology
      Institute (NMI) of Mexico, The proposed method uses a vision system to align the
      scale mark of the hydrometer to the surface of the liquid where it is immersed by
      implementing image processing algorithms. This approach reduces the variability
      in the apparent mass determination during the hydrostatic weighing in the
      calibration process, therefore decreasing the relative uncertainty of
      calibration. 

PMID- 24284771
TI  - A generalized pyramid matching kernel for human action recognition in realistic
      videos.
AB  - Human action recognition is an increasingly important research topic in the
      fields of video sensing, analysis and understanding. Caused by unconstrained
      sensing conditions, there exist large intra-class variations and inter-class
      ambiguities in realistic videos, which hinder the improvement of recognition
      performance for recent vision-based action recognition systems. In this paper, we
      propose a generalized pyramid matching kernel (GPMK) for recognizing human
      actions in realistic videos, based on a multi-channel "bag of words"
      representation constructed from local spatial-temporal features of video clips.
      As an extension to the spatial-temporal pyramid matching (STPM) kernel, the GPMK
      leverages heterogeneous visual cues in multiple feature descriptor types and
      spatial-temporal grid granularity levels, to build a valid similarity metric
      between two video clips for kernel-based classification. Instead of the
      predefined and fixed weights used in STPM, we present a simple, yet effective,
      method to compute adaptive channel weights of GPMK based on the kernel target
      alignment from training data. It incorporates prior knowledge and the data-driven
      information of different channels in a principled way. The experimental results
      on three challenging video datasets (i.e., Hollywood2, Youtube and HMDB51)
      validate the superiority of our GPMK w.r.t. the traditional STPM kernel for
      realistic human action recognition and outperform the state-of-the-art results in
      the literature. 

PMID- 24284773
TI  - Performance of a distributed simultaneous strain and temperature sensor based on
      a Fabry-Perot laser diode and a dual-stage FBG optical demultiplexer.
AB  - A simultaneous strain and temperature measurement method using a Fabry-Perot
      laser diode (FP-LD) and a dual-stage fiber Bragg grating (FBG) optical
      demultiplexer was applied to a distributed sensor system based on Brillouin
      optical time domain reflectometry (BOTDR). By using a Kalman filter, we improved
      the performance of the FP-LD based OTDR, and decreased the noise using the dual
      stage FBG optical demultiplexer. Applying the two developed components to the
      BOTDR system and using a temperature compensating algorithm, we successfully
      demonstrated the simultaneous measurement of strain and temperature distributions
      under various experimental conditions. The observed errors in the temperature and
      strain measured using the developed sensing system were 0.6  degrees C and 50
      MUepsilon, and the spatial resolution was 1 m, respectively. 

PMID- 24284774
TI  - Accurate estimation of airborne ultrasonic time-of-flight for overlapping echoes.
AB  - In this work, an analysis of the transmission of ultrasonic signals generated by
      piezoelectric sensors for air applications is presented. Based on this analysis,
      an ultrasonic response model is obtained for its application to the recognition
      of objects and structured environments for navigation by autonomous mobile
      robots. This model enables the analysis of the ultrasonic response that is
      generated using a pair of sensors in transmitter-receiver configuration using the
      pulse-echo technique. This is very interesting for recognizing surfaces that
      simultaneously generate a multiple echo response. This model takes into account
      the effect of the radiation pattern, the resonant frequency of the sensor, the
      number of cycles of the excitation pulse, the dynamics of the sensor and the
      attenuation with distance in the medium. This model has been developed,
      programmed and verified through a battery of experimental tests. Using this model
      a new procedure for obtaining accurate time of flight is proposed. This new
      method is compared with traditional ones, such as threshold or correlation, to
      highlight its advantages and drawbacks. Finally the advantages of this method are
      demonstrated for calculating multiple times of flight when the echo is formed by
      several overlapping echoes. 

PMID- 24284772
TI  - Short chain N-acylhomoserine lactone production by clinical multidrug resistant
      Klebsiella pneumoniae strain CSG20.
AB  - Klebsiella pneumoniae is one of the most common Gram-negative bacterial pathogens
      in clinical practice. It is associated with a wide range of disorders, ranging
      from superficial skin and soft tissue infections to potentially fatal sepsis in
      the lungs and blood stream. Quorum sensing, or bacterial cell-cell communication,
      refers to population density-dependent gene expression modulation. Quorum sensing
      in Proteobacteria relies on the production and sensing of signaling molecules
      which are mostly N-acylhomoserine lactones. Here, we report the identification of
      a multidrug resistant clinical isolate, K. pneumoniae strain CSG20, using matrix
      assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass
      spectrometry. We further confirmed quorum sensing activity in this strain with
      the use of high resolution tandem liquid chromatography quadrupole mass
      spectrometry and provided evidence K. pneumoniae strain CSG20 produced N-hexanoyl
      homoserine lactone (C6-HSL). To the best of our knowledge, this is the first
      report on the production of N-hexanoylhomoserine lactone (C6-HSL) in clinical
      isolate K. pneumoniae. 

PMID- 24284775
TI  - Development and evaluation of an improved technique for pulmonary function
      testing using electrical impedance pneumography intended for the diagnosis of
      chronic obstructive pulmonary disease patients.
AB  - Spirometry is regarded as the only effective method for detecting pulmonary
      function test (PFT) indices. In this study, a novel impedance pulmonary function
      measurement system (IPFS) is developed for directly assessing PFT indices. IPFS
      can obtain high resolution values and remove motion artifacts through real-time
      base impedance feedback. Feedback enables the detection of PFT indices using only
      both hands for convenience. IPFS showed no differences in the sitting, supine,
      and standing postures during the measurements, indicating that patient posture
      has no effect on IPFS. Mean distance analysis showed good agreement between the
      volume and flow signal of IPFS (p < 0.05). PFT indices were detected in subjects
      to differentiate a chronic obstructive pulmonary disease (COPD) patient group
      from a normal group. The forced vital capacity (FVC), forced expiratory volume in
      the first second (FEV1), FEV1/FVC, and peak expiratory flow (PEF) in the COPD
      group were lower than those in the normal group by IPFS (p < 0.05). IPFS is
      therefore suitable for evaluating pulmonary function in normal and COPD patients.
      Moreover, IPFS could be useful for periodic monitoring of existing patients
      diagnosed with obstructive lung disease. 

PMID- 24284777
TI  - Association between preoperative 25-hydroxyvitamin D level and hospital-acquired
      infections following Roux-en-Y gastric bypass surgery.
AB  - IMPORTANCE: Postoperative hospital-acquired infections (HAIs) may result from
      disruption of natural barrier sites. Recent studies have linked vitamin D status
      and barrier site integrity. OBJECTIVE: To investigate the association between
      preoperative vitamin D status and the risk for HAIs. DESIGN, SETTING, AND
      PARTICIPANTS: A retrospective analysis was performed using propensity score
      methods to construct a matched-pairs cohort to reduce baseline differences
      between patients with 25-hydroxyvitamin D (25[OH]D) levels less than 30 ng/mL vs
      30 ng/mL or greater. Multivariable logistic regression analysis was then
      performed to examine the association between 25(OH)D levels and HAIs while
      adjusting for additional perioperative factors. Locally weighted scatterplot
      smoothing was used to depict the relationship between increasing 25(OH)D levels
      and the risk for HAIs. This study was conducted in a single, teaching hospital in
      Boston, Massachusetts, and involved 770 gastric bypass surgery patients between
      January 1, 2007, and December 31, 2011. EXPOSURES: Preoperative 25(OH)D levels.
      MAIN OUTCOMES AND MEASURES: Association between preoperative 25(OH)D levels and
      the risk for postoperative HAIs. RESULTS: The risk for HAIs was 3-fold greater
      (adjusted odds ratio, 3.05; 95% CI, 1.34-6.94) in patients with 25(OH)D levels
      less than 30 ng/mL vs 30 ng/mL or greater. Further adjustment for additional
      perioperative factors did not materially change this association. Locally
      weighted scatterplot smoothing analysis depicted a near inverse linear
      relationship between vitamin D status and the risk for HAIs for 25(OH)D levels
      around 30 ng/mL. CONCLUSIONS AND RELEVANCE: In our patient cohort, a significant
      inverse association was observed between preoperative 25(OH)D levels and the risk
      for HAIs. These results suggest that preoperative 25(OH)D levels may be a
      modifiable risk factor for postoperative nosocomial infections. Prospective
      studies must determine whether there is a potential benefit to preoperative
      optimization of vitamin D status.

PMID- 24284778
TI  - Behavior of phosphorous and contaminants from molecular doping combined with a
      conventional spike annealing method.
AB  - The fabrication of future nanoscale semiconductor devices calls for precise
      placement of dopant atoms into their crystal lattice. Monolayer doping combined
      with a conventional spike annealing method provides a bottom-up approach
      potentially viable for large scale production. While the diffusion of the dopant
      was demonstrated at the start of the method, more sophisticated techniques are
      required in order to understand the diffusion, at the near surface, of P and
      contaminants such as C and O carried by the precursor, not readily accessible to
      direct time-of-flight secondary ion mass spectrometry measurements. By employing
      atom probe tomography, we report on the behavior of dopant and contaminants
      introduced by the molecular monolayer doping method into the first nanometers.
      The unwanted diffusion of C and O-related molecules is revealed and it is shown
      that for C and O it is limited to the first monolayers, where Si-C bonding
      formation is also observed, irrespective of the spike annealing temperature. From
      the perspective of large scale employment, our results suggest the benefits of
      adding a further process to the monolayer doping combined with spike annealing
      method, which consists of removing a sacrificial Si layer to eliminate
      contaminants. 

PMID- 24284779
TI  - Prevalence and characterization of human mecC methicillin-resistant
      Staphylococcus aureus isolates in England.
AB  - OBJECTIVES: There are limited data available on the epidemiology and prevalence
      of methicillin-resistant Staphylococcus aureus (MRSA) in the human population
      that encode the recently described mecA homologue, mecC. To address this
      knowledge gap we undertook a prospective prevalence study in England to determine
      the prevalence of mecC among MRSA isolates. PATIENTS AND METHODS: Three hundred
      and thirty-five sequential MRSA isolates from individual patients were collected
      from each of six clinical microbiology laboratories in England during 2011-12.
      These were tested by PCR or genome sequencing to differentiate those encoding
      mecA and mecC. mecC-positive isolates were further characterized by multilocus
      sequence typing, spa typing, antimicrobial susceptibility profile and detection
      of PBP2a using commercially available kits. RESULTS: Nine out of the 2010 MRSA
      isolates tested were mecC positive, indicating a prevalence among MRSA in England
      of 0.45% (95% CI 0.24%-0.85%). The remainder were mecA positive. Eight out of
      these nine mecC MRSA isolates belonged to clonal complex 130, the other being
      sequence type 425. Resistance to non-beta-lactam antibiotics was rare among these
      mecC MRSA isolates and all were phenotypically identified as MRSA using oxacillin
      and cefoxitin according to BSAC disc diffusion methodology. However, all nine
      mecC isolates gave a negative result using three different commercial PBP2a
      detection assays. CONCLUSIONS: mecC MRSA are currently rare among MRSA isolated
      from humans in England and this study provides an important baseline prevalence
      rate to monitor future changes, which may be important given the increasing
      prevalence of mecC MRSA reported in Denmark.

PMID- 24284780
TI  - Repurposing as a means to increase the activity of amphotericin B and caspofungin
      against Candida albicans biofilms.
AB  - OBJECTIVES: Biofilms of Candida species, often formed on medical devices, are
      generally resistant to currently available antifungal drugs. The aim of this
      study was to identify compounds that increase the activity of amphotericin B and
      caspofungin, commonly used antifungal agents, against Candida biofilms. METHODS:
      A library containing off-patent drugs was screened for compounds, termed
      enhancers, that increase the in vitro activity of amphotericin B against Candida
      albicans biofilms. Biofilms were grown in 96-well plates and growth was
      determined by the cell titre blue assay. Synergy between identified enhancers and
      antifungal agents was further characterized in vitro using fractional inhibitory
      concentration index (FICI) values and in vivo using a worm biofilm infection
      model. In light of the application of these enhancers onto implants, their
      possible effect on the growth potential of MG63 osteoblast-like cells was
      assessed. RESULTS: Pre-incubation of C. albicans biofilms with subinhibitory
      concentrations of the enhancers drospirenone, perhexiline maleate or toremifene
      citrate significantly increased the activity of amphotericin B or caspofungin
      (FICI  < 0.5) against C. albicans and Candida glabrata biofilms. Moreover, these
      enhancers did not affect the growth potential of osteoblasts. Interestingly,
      toremifene citrate also enhanced the in vitro activity of caspofungin in a mixed
      biofilm consisting of C. albicans and Staphylococcus epidermidis. Furthermore, we
      demonstrate synergy between toremifene citrate and caspofungin in an in vivo worm
      C. albicans biofilm infection model. CONCLUSIONS: Our data demonstrate an in
      vitro and in vivo enhancement of the antibiofilm activity of caspofungin by
      toremifene citrate. Furthermore, our results pave the way for implant-related
      applications of the identified enhancers.

PMID- 24284782
TI  - MBE-grown Si and Si(1-x)Ge(x) quantum dots embedded within epitaxial Gd2O3 on
      Si(111) substrate for floating gate memory device.
AB  - Si and Si(1-x)Ge(x) quantum dots embedded within epitaxial Gd2O3 grown by
      molecular beam epitaxy have been studied for application in floating gate memory
      devices. The effect of interface traps and the role of quantum dots on the memory
      properties have been studied using frequency-dependent capacitance-voltage and
      conductance-voltage measurements. Multilayer quantum dot memory comprising four
      and five layers of Si quantum dots exhibits a superior memory window to that of
      single-layer quantum dot memory devices. It has also been observed that single
      layer Si(1-x)Ge(x) quantum dots show better memory characteristics than single
      layer Si quantum dots.

PMID- 24284781
TI  - Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA
      for the detection of drug resistance prior to starting first-line antiretroviral
      therapy with etravirine or efavirenz.
AB  - OBJECTIVES: This study investigated strategies that may increase the yield of
      drug resistance testing prior to starting antiretroviral therapy (ART), and
      whether transmitted and polymorphic resistance-associated mutations (RAMs)
      correlated with virological outcomes. METHODS: We carried out retrospective
      testing of baseline samples from patients entering the SENSE trial of first-line
      ART in Europe, Russia and Israel. Prior to randomization to etravirine or
      efavirenz plus two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), plasma
      samples underwent routine Sanger sequencing of HIV-1 RT and protease ((plasma)SS)
      in order to exclude patients with transmitted RAMs. Retrospectively, Sanger
      sequencing was repeated with HIV-1 DNA from baseline peripheral blood mononuclear
      cells (PBMCSS); baseline plasma samples were retested by allele-specific PCR
      targeting seven RT RAMs (AS-PCR) and ultra-deep RT sequencing (UDS). RESULTS: By
      (plasma)SS, 16/193 (8.3%) patients showed >= 1 transmitted RAM affecting the
      NRTIs (10/193, 5.2%), non-nucleoside reverse transcriptase inhibitors (4/193,
      2.1%) or protease inhibitors (2/193, 1.0%). No additional RAMs were detected by
      AS-PCR (n = 152) and UDS (n = 24); PBMCSS (n =  91) yielded two additional
      samples with one RAM each. Over 48 weeks, 4/79 (5.1%) patients on etravirine and
      7/78 (9.0%) on efavirenz experienced virological failure; none had baseline RAMs.
      Conversely, 11/79 (13.9%) patients randomized to etravirine had one polymorphic
      RAM from the etravirine score in baseline plasma (V90I, V106I or E138A), without
      any impact on virological outcomes. CONCLUSIONS: The detection of resistance
      increased marginally with PBMC testing but did not increase with sensitive plasma
      testing. A careful consideration is required of the cost-effectiveness of
      different strategies for baseline HIV drug resistance testing.

PMID- 24284783
TI  - beta-Elemene, a compound derived from Rhizoma zedoariae, reverses multidrug
      resistance mediated by the ABCB1 transporter.
AB  - In the present in vitro study, we examined the effect of the compound beta
      elemene on the response of KB-C2 cells overexpressing the ABCB1 transporter to
      specific antineoplastic compounds. The MTT assay was used to determine the
      effects of beta-elemene in combination with other anticancer drugs on ABCB1
      overexpressing cancer cell lines. Furthermore, we used [3H]-paclitaxel
      accumulation, efflux assay, immunofluorescence experiments, western blot assays
      and docking analysis to ascertain the mechanism of action of beta-elemene. The
      incubation of KB-C2 cells overexpressing ABCB1 transporter with beta-elemene (100
      uM) significantly augmented the antineoplastic efficacy of colchicine,
      vinblastine and paclitaxel when compared to KB-C2 cells incubated with these
      drugs alone. In HEK293 cells overexpressing the ABCB1 transporter, beta-elemene
      significantly increased the cytotoxicity of paclitaxel. In addition, 100 uM of
      beta-elemene significantly increased the accumulation of [3H]-paclitaxel and this
      was due to a decrease in [3H]-paclitaxel efflux when compared to controls. The
      incubation of KB-C2 cells with beta-elemene (100 uM) for 72 h did not
      significantly alter the expression of ABCB1 protein levels. Immunofluorescence
      experiments indicated that beta-elemene did not significantly alter the
      subcellular localization of the ABCB1 transporter. Docking analysis indicated
      that beta-elemene binds to the drug-binding site of ABCB1 transporter. Finally,
      beta-elemene at 100 uM partially (~50%) increased the sensitivity of the BCRP
      overexpressing cell line, NCI-H460/MX20, to mitoxantrone, but beta-elemene did
      not significantly alter the resistance of MRP1-transfected HEK293/MRP1 cells to
      vincristine. Overall, our in vitro findings indicated that beta-elemene
      potentiates the cytotoxic effects of various antineoplastic drugs in cell lines
      overexpressing the ABCB1 transporter and that this is due to the inhibition of
      the efflux component of the ABCB1 transporter.

PMID- 24284784
TI  - Fear of falling after hip fracture in vulnerable older persons rehabilitating in
      a skilled nursing facility.
AB  - OBJECTIVE: To identify factors that explain differences in patients with high and
      low levels of fear of falling after a hip fracture. DESIGN: Cross-sectional study
      in 10 skilled nursing facilities in the Netherlands. PATIENTS: A total of 100
      patients aged >= 65 years admitted to a skilled nursing facility after a hip
      fracture. METHODS: Participants were divided into 2 groups; low and high level of
      fear of falling, based on median Falls Efficacy Score - International. Data
      relating to factors that might explain fear of falling were collected, including
      demographic variables, aspects of functioning, psychological factors, and
      comorbidities. For every factor a univariate logistic regression was conducted.
      For the multivariate regression model a backward procedure was used in which
      variables with p < 0.05 were included. RESULTS: Walking ability and activities of
      daily living before fracture, number of complications, activities of daily living
      after fracture, anxiety and self-efficacy were significantly associated
      univariately with fear of falling. Multivariate analysis showed that walking
      ability before fracture (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.14
      0.83), activities of daily living after fracture (OR 0.89, 95% CI 0.80-0.99), and
      anxiety (OR 1.22, 95% CI 1.05-1.42) were independently associated with fear of
      falling. CONCLUSION: Impaired walking ability before fracture, impaired
      activities of daily living after fracture, and increased anxiety help distinguish
      between older persons with high and low levels of fear of falling after hip
      fracture. Because the last 2 factors are modifiable, this information enables the
      development of specific interventions for older persons with a high level of fear
      of falling.

PMID- 24284785
TI  - Dynamic changes in ribosome-associated proteome and phosphoproteome during
      deoxynivalenol-induced translation inhibition and ribotoxic stress.
AB  - Deoxynivalenol (DON), a trichothecene mycotoxin produced by Fusarium that
      commonly contaminates cereal-based food, interacts with the ribosome to cause
      translation inhibition and activate stress kinases in mononuclear phagocytes via
      the ribotoxic stress response (RSR). The goal of this study was to test the
      hypothesis that the ribosome functions as a platform for spatiotemporal
      regulation of translation inhibition and RSR. Specifically, we employed stable
      isotope labeling of amino acids in cell culture (SILAC)-based proteomics to
      quantify the early (<= 30 min) DON-induced changes in ribosome-associated
      proteins in RAW 264.7 murine macrophage. Changes in the proteome and
      phosphoproteome were determined using off-gel isoelectric focusing and titanium
      dioxide chromatography, respectively, in conjunction with LC-MS/MS. Following
      exposure of RAW 264.7 to a toxicologically relevant concentration of DON (250
      ng/ml), we observed an overall decrease in translation-related proteins
      interacting with the ribosome, concurrently with a compensatory increase in
      proteins that mediate protein folding, biosynthesis, and cellular organization.
      Alterations in the ribosome-associated phosphoproteome reflected proteins that
      modulate translational and transcriptional regulation, and others that converged
      with signaling pathways known to overlap with phosphorylation changes
      characterized previously in intact RAW 264.7 cells. These results suggest that
      the ribosome plays a central role as a hub for association and phosphorylation of
      proteins involved in the coordination of early translation inhibition as well as
      recruitment and maintenance of stress-related proteins-both of which enable cells
      to adapt and respond to ribotoxin exposure. This study provides a template for
      elucidating the molecular mechanisms of DON and other ribosome-targeting agents.

PMID- 24284786
TI  - The analysis of goldfish (Carassius auratus L.) innate immune responses after
      acute and subchronic exposures to oil sands process-affected water.
AB  - We examined the immunotoxic effects of acute and subchronic exposures of goldfish
      to aged, fresh, and ozonated oil sands process-affected water (OSPW) using a flow
      through exposure apparatus. We measured the expression of proinflammatory
      cytokine genes, the antimicrobial responses of primary macrophages isolated from
      OSPW-exposed fish, and the ability of the goldfish to control infection with a
      protozoan parasite, Trypanosoma carassii. After acute (1 week) exposure to aged
      OSPW, we observed upregulation in the expression of interferon gamma (IFN-gamma),
      tumor necrosis factor alpha-2 (TNF-alpha2) in the kidney and spleen but not in
      gills of the fish. After subchronic (12 weeks) exposure to aged OSPW, we observed
      significant increases in mRNA levels of proinflammatory genes in the gill (IFN
      gamma, interleukin-1 beta 1 [IL1-beta1], TNF-alpha2), kidney (IL1-beta1, TNF
      alpha2), and spleen (IL1-beta1). An upregulation of immune gene expression in the
      gill and kidney (IFN-gamma, IL1-beta1, TNF-alpha2) and spleen (IL1-beta1, TNF
      alpha2) was observed after acute exposure of fish to diluted fresh OSPW.
      Following subchronic exposure to diluted fresh OSPW, we observed high mRNA levels
      of IL1-beta1 in all tissues examined. However, there were significant decreases
      in the mRNA levels of IFN-gamma and TNF-alpha2 in the kidney and spleen and gill
      and spleen (IL-12p35 and IL-12p40) of exposed fish. There were no changes in the
      expression of anti-inflammatory cytokine IL-10 after both acute and subchronic
      exposures to diluted fresh OSPW. In fish exposed to ozonated fresh OSPW, immune
      gene expression was similar to nonexposed control fish in all organs examined,
      with exception of IL1-beta1. The ability of primary kidney macrophages to
      generate reactive oxygen and nitrogen intermediates was significantly reduced in
      fish exposed to fresh OSPW. The enhanced proinflammatory response after acute
      exposure to diluted fresh OSPW was confirmed by the parasite challenge
      experiments, where OSPW-exposed fish controlled the infection better than
      nonexposed fish. 

PMID- 24284787
TI  - Differential response to abiraterone acetate and di-n-butyl phthalate in an
      androgen-sensitive human fetal testis xenograft bioassay.
AB  - In utero exposure to antiandrogenic xenobiotics such as di-n-butyl phthalate
      (DBP) has been linked to congenital defects of the male reproductive tract,
      including cryptorchidism and hypospadias, as well as later life effects such as
      testicular cancer and decreased sperm counts. Experimental evidence indicates
      that DBP has in utero antiandrogenic effects in the rat. However, it is unclear
      whether DBP has similar effects on androgen biosynthesis in human fetal testis.
      To address this issue, we developed a xenograft bioassay with multiple androgen
      sensitive physiological endpoints, similar to the rodent Hershberger assay. Adult
      male athymic nude mice were castrated, and human fetal testis was xenografted
      into the renal subcapsular space. Hosts were treated with human chorionic
      gonadotropin for 4 weeks to stimulate testosterone production. During weeks 3 and
      4, hosts were exposed to DBP or abiraterone acetate, a CYP17A1 inhibitor.
      Although abiraterone acetate (14 d, 75 mg/kg/d po) dramatically reduced
      testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500
      mg/kg/d po) had no effect on androgenic endpoints. DBP did produce a near
      significant trend toward increased multinucleated germ cells in the xenografts.
      Gene expression analysis showed that abiraterone decreased expression of genes
      related to transcription and cell differentiation while increasing expression of
      genes involved in epigenetic control of gene expression. DBP induced expression
      of oxidative stress response genes and altered expression of actin cytoskeleton
      genes.

PMID- 24284788
TI  - Membrane-bound metallothionein 1 of murine dendritic cells promotes the expansion
      of regulatory T cells in vitro.
AB  - Exposure to environmental toxicants can alter a range of cellular functions
      involved in the immune response. Increased expression of the stress protein
      metallothionein 1 (MT1) is one example hereof. Previously, it has been reported
      that MT1 has several immunosuppressive properties. Furthermore, we earlier showed
      that functionally tolerogenic dendritic cells (DCs) expressed increased mRNA
      levels of MT1. Here, we demonstrate that dexamethasone-treated murine DCs are
      functionally tolerogenic and produce MT1. However, these DCs do not actively
      transport MT1 to the cell membrane and their regulatory function does not depend
      on MT1. Alternatively, ZnCl2-treated murine DCs transport MT1 to the cell surface
      are tolerogenic and promote the expansion of T cells with a regulatory phenotype.
      Moreover, the membrane-bound MT1 was shown to be essential for ZnCl2-treated DCs
      to exert their regulatory function. On the basis of this, MT1 can be used as a
      new marker for functionally tolerogenic DCs. Additionally, we have found a new
      mechanism for tolerogenic DCs to exert their immune regulatory function. 

PMID- 24284789
TI  - A comparative study of different in vitro lung cell culture systems to assess the
      most beneficial tool for screening the potential adverse effects of carbon
      nanotubes.
AB  - To determine the potential inhalatory risk posed by carbon nanotubes (CNTs), a
      tier-based approach beginning with an in vitro assessment must be adopted. The
      purpose of this study therefore was to compare 4 commonly used in vitro systems
      of the human lung (human blood monocyte-derived macrophages [MDM] and monocyte
      derived dendritic cells [MDDC], 16HBE14o- epithelial cells, and a sophisticated
      triple cell co-culture model [TCC-C]) via assessment of the biological impact of
      different CNTs (single-walled CNTs [SWCNTs] and multiwalled CNTs [MWCNTs]) over
      24h. No significant cytotoxicity was observed with any of the cell types tested,
      although a significant (p < .05), dose-dependent increase in tumor necrosis
      factor (TNF)-alpha following SWCNT and MWCNT exposure at concentrations up to
      0.02mg/ml to MDM, MDDC, and the TCC-C was found. The concentration of TNF-alpha
      released by the MDM and MDDC was significantly higher (p < .05) than the TCC-C.
      Significant increases (p < .05) in interleukin (IL)-8 were also found for both
      16HBE14o- epithelial cells and the TCC-C after SWCNTs and MWCNTs exposure up to
      0.02mg/ml. The TCC-C, however, elicited a significantly (p < .05) higher IL-8
      release than the epithelial cells. The oxidative potential of both SWCNTs and
      MWCNTs (0.005-0.02mg/ml) measured by reduced glutathione (GSH) content showed a
      significant difference (p < .05) between each monoculture and the TCC-C. It was
      concluded that because only the co-culture system could assess each endpoint
      adequately, that, in comparison with monoculture systems, multicellular systems
      that take into consideration important cell type-to-cell type interactions could
      be used as predictive in vitro screening tools for determining the potential
      deleterious effects associated with CNTs. 

PMID- 24284790
TI  - Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an
      additive manner.
AB  - Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of
      EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER),
      ERalpha and ERbeta, and may contribute to estrogen-linked diseases such as breast
      cancer. Early exposure is of particular concern; many EDCs cross the placenta and
      infants have measurable levels of, eg, BPA. In addition, infants are frequently
      fed soy-based formula (SF) that contains phytoestrogens. Effects of combined
      exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively
      compared to what extent BPA, genistein, and an extract of infant SF mimic
      estrogen-induced gene transcription and cell proliferation. We investigated
      ligand-specific effects on ER activation in HeLa-ERalpha and ERbeta reporter
      cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects
      in MCF7 breast cancer cells; and how coexposure influenced these effects. The
      biological relevance was explored using enrichment analyses of differentially
      regulated genes and clustering with clinical breast cancer profiles. We
      demonstrate that coexposure to BPA and genistein, or SF, results in increased
      functional and transcriptional estrogenic effects. Using statistical modeling, we
      determine that BPA and phytoestrogens act in an additive manner. The
      proliferative and transcriptional effects of the tested compounds mimic those of
      17beta-estradiol, and are abolished by cotreatment with an ER antagonist. Gene
      expression profiles induced by each compound clustered with poor prognosis breast
      cancer, indicating that exposure may adversely affect breast cancer prognosis.
      This study accentuates that coexposure to BPA and soy-based phytoestrogens
      results in additive estrogenic effects, and may contribute to estrogen-linked
      diseases, including breast cancer. 

PMID- 24284791
TI  - Influenza vaccine response in adults exposed to perfluorooctanoate and
      perfluorooctanesulfonate.
AB  - Supported by several epidemiological studies and a large number of animal
      studies, certain polyfluorinated alkyl acids are believed to be immunotoxic,
      affecting particularly humoral immunity. Our aim was to investigate the
      relationship between the antibody response following vaccination with an
      inactivated trivalent influenza vaccine and circulating levels of
      perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). The study
      population consisted of 411 adults living in the mid-Ohio region of Ohio and West
      Virginia where public drinking water had been inadvertently contaminated with
      PFOA. They participated in a larger cross-sectional study in 2005/2006 and were
      followed up in 2010, by which time serum levels of PFOA had been substantially
      reduced but were still well above those found in the general population.
      Hemagglutination inhibition tests were conducted on serum samples collected
      preinfluenza vaccination and 21 +/- 3 days postvaccination in 2010. Serum samples
      were also analyzed for PFOA and PFOS concentrations (median: 31.5 and 9.2 ng/ml,
      respectively). Questionnaires were conducted regarding the occurrence and
      frequency of recent (during the last 12 months) respiratory infections. Our
      findings indicated that elevated PFOA serum concentrations are associated with
      reduced antibody titer rise, particularly to A/H3N2 influenza virus, and an
      increased risk of not attaining the antibody threshold considered to offer long
      term protection. Although the direct relationship between weakened antibody
      response and clinical risk of influenza is not clear, we did not find evidence
      for an association between self-reported colds or influenza and PFOA levels nor
      between PFOS serum concentrations and any of the endpoints examined.

PMID- 24284793
TI  - BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem
      cells.
AB  - While white adipose tissue (AT) is an energy storage depot, brown AT is
      specialized in energy dissipation. Uncoupling protein 1 (UCP1)-expressing
      adipocytes with a different origin than classical brown adipocytes have been
      found in white AT. These "brite" (brown-in-white) adipocytes may represent a
      therapeutic target to counteract obesity. Bone morphogenetic proteins (BMPs) play
      a role in the regulation of adipogenesis. Based on studies with murine cells,
      BMP4 is assumed to induce stem cell commitment to the white adipocyte lineage,
      whereas BMP7 promotes brown adipogenesis. There is evidence for discrepancies
      between mouse and human AT. Therefore, we compared the effect of BMP4 and BMP7 on
      white-to-brown transition in primary human adipose stem cells (hASCs) from
      subcutaneous AT. Long-term exposure of hASCs to recombinant BMP4 or BMP7 during
      differentiation increased adipogenesis, as determined by lipid accumulation and
      peroxisome proliferator-activated receptor-gamma (PPARgamma) expression. Not only
      BMP7, but also BMP4, increased UCP1 expression in hASCs and decreased expression
      of the white-specific marker TCF21. The ability of hASCs to induce UCP1 in
      response to BMP4 and BMP7 markedly differed between donors and could be related
      to the expression of the brite marker CD137. However, mitochondrial content and
      oxygen consumption were not increased in hASCs challenged with BMP4 and BMP7. In
      conclusion, we showed for the first time that BMP4 has similar effects on white
      to-brown transition as BMP7 in our human cell model. Thus the roles of BMP4 and
      BMP7 in adipogenesis cannot always be extrapolated from murine to human cell
      models. 

PMID- 24284792
TI  - Prostaglandin E2 induces chloride secretion through crosstalk between cAMP and
      calcium signaling in mouse inner medullary collecting duct cells.
AB  - Under conditions of high dietary salt intake, prostaglandin E2 (PGE2) production
      is increased in the collecting duct and promotes urinary sodium chloride (NaCl)
      excretion; however, the molecular mechanisms by which PGE2 increases NaCl
      excretion in this context have not been clearly defined. We used the mouse inner
      medullary collecting duct (mIMCD)-K2 cell line to characterize mechanisms
      underlying PGE2-regulated NaCl transport. When epithelial Na(+) channels were
      inhibited, PGE2 exclusively stimulated basolateral EP4 receptors to increase
      short-circuit current (Isc(PGE2)). We found that Isc(PGE2) was sensitive to
      inhibition by H-89 and CFTR-172, indicating that EP4 receptors signal through
      protein kinase A to induce Cl(-) secretion via cystic fibrosis transmembrane
      conductance regulator (CFTR). Unexpectedly, we also found that Isc(PGE2) was
      sensitive to inhibition by BAPTA-AM (Ca(2+) chelator), 2-aminoethoxydiphenyl
      borate (2-APB) (inositol triphosphate receptor blocker), and flufenamic acid
      (FFA) [Ca(2+)-activated Cl(-) channel (CACC) inhibitor], suggesting that EP4
      receptors also signal through Ca(2+) to induce Cl(-) secretion via CACC.
      Additionally, we observed that PGE2 stimulated an increase in Isc through
      crosstalk between cAMP and Ca(2+) signaling; BAPTA-AM or 2-APB inhibited a
      component of Isc(PGE2) that was sensitive to CFTR-172 inhibition; H-89 inhibited
      a component of Isc(PGE2) that was sensitive to FFA inhibition. Together, our
      findings indicate that PGE2 activates basolateral EP4 receptors and signals
      through both cAMP and Ca(2+) to stimulate Cl(-) secretion in IMCD-K2 cells. We
      propose that these signaling pathways, and the crosstalk between them, may
      provide a concerted mechanism for enhancing urinary NaCl excretion under
      conditions of high dietary NaCl intake. 

PMID- 24284794
TI  - Dynamic adhesion of eryptotic erythrocytes to immobilized platelets via platelet
      phosphatidylserine receptors.
AB  - Glucose depletion of erythrocytes triggers suicidal erythrocyte death or
      eryptosis, which leads to cell membrane scrambling with phosphatidylserine
      exposure at the cell surface. Eryptotic erythrocytes adhere to endothelial cells
      by a mechanism involving phosphatidylserine at the erythrocyte surface and CXCL16
      as well as CD36 at the endothelial cell membrane. Nothing has hitherto been known
      about an interaction between eryptotic erythrocytes and platelets, the decisive
      cells in primary hemostasis and major players in thrombotic vascular occlusion.
      The present study thus explored whether and how glucose-depleted erythrocytes
      adhere to platelets. To this end, adhesion of phosphatidylserine-exposing
      erythrocytes to platelets under flow conditions was examined in a flow chamber
      model at arterial shear rates. Platelets were immobilized on collagen and further
      stimulated with adenosine diphosphate (ADP, 10 MUM) or thrombin (0.1 U/ml). As a
      result, a 48-h glucose depletion triggered phosphatidylserine translocation to
      the erythrocyte surface and augmented the adhesion of erythrocytes to immobilized
      platelets, an effect significantly increased upon platelet stimulation. Adherence
      of erythrocytes to platelets was blunted by coating of erythrocytic
      phosphatidylserine with annexin V or by neutralization of platelet
      phosphatidylserine receptors CXCL16 and CD36 with respective antibodies. In
      conclusion, glucose-depleted erythrocytes adhere to platelets. The adhesive
      properties of platelets are augmented by platelet activation. Erythrocyte
      adhesion to immobilized platelets requires phosphatidylserine at the erythrocyte
      surface and CXCL16 as well as CD36 expression on platelets. Thus platelet
      mediated erythrocyte adhesion may foster thromboocclusive complications in
      diseases with stimulated phosphatidylserine exposure of erythrocytes. 

PMID- 24284795
TI  - p53 is necessary for the adaptive changes in cellular milieu subsequent to an
      acute bout of endurance exercise.
AB  - An acute bout of exercise activates downstream signaling cascades that ultimately
      result in mitochondrial biogenesis. In addition to inducing mitochondrial
      synthesis, exercise triggers the removal of damaged cellular material via
      autophagy and of dysfunctional mitochondria through mitophagy. Here, we
      investigated the necessity of p53 to the changes that transpire within the muscle
      upon an imposed metabolic and physiological challenge, such as a bout of
      endurance exercise. We randomly assigned wild-type (WT) and p53 knockout (KO)
      mice to control, acute exercise (AE; 90 min at 15 m/min), and AE + 3 h recovery
      (AER) groups and measured downstream alterations in markers of mitochondrial
      biogenesis, autophagy, and mitophagy. In the absence of p53, activation of p38
      MAPK upon exercise was abolished, whereas CaMKII and AMP-activated protein kinase
      only displayed an attenuated enhancement in the AER group compared with WT mice.
      The translocation of peroxisome proliferator-activated receptor-gamma coactivator
      1 alpha to the nucleus was diminished and only observed in the AER group, and the
      subsequent increase in messenger RNA transcripts related to mitochondrial
      biogenesis with exercise and recovery was absent in the p53 KO animals. Whole
      muscle autophagic and lysosomal markers did not respond to exercise, irrespective
      of the genotype of the exercised mice, with the exception of increased
      ubiquitination observed in KO mice with exercise. Markers of mitophagy were
      elevated in response to AE and AER conditions in both WT and p53 KO runners. The
      data suggest that p53 is important for the exercise-induced activation of
      mitochondrial synthesis and is integral in regulating autophagy during control
      conditions but not in response to exercise. 

PMID- 24284796
TI  - Enhanced endoplasmic reticulum SERCA activity by overexpression of hepatic
      stimulator substance gene prevents hepatic cells from ER stress-induced
      apoptosis.
AB  - Although the potential pathogenesis of nonalcoholic fatty liver disease (NAFLD)
      is unclear, increasing evidence indicates that endoplasmic reticulum (ER) stress
      may link free fatty acids to NAFLD. Since we previously reported that hepatic
      stimulator substance (HSS) could protect the liver from steatosis, this study is
      aimed to investigate whether HSS protection could be related with its inhibition
      on ER stress. The HSS gene was stably transfected into BEL-7402 hepatoma cells
      and effectively expressed in ER. The palmitic acid (PA)-induced heptocyte
      lipotoxicity was reproduced in the HSS-transfected cells, and HSS alleviation of
      the ER stress and apoptosis were subsequently examined. The results showed that
      PA treatment led to a heavy accumulation of fatty acids within the cells and a
      remarkable increase in reactive oxygen species (ROS). However, in the HSS
      expressing cells, production of ROS was inhibited and ER stress-related marker
      glucose-regulated protein 78 (GRP-78), sterol regulatory element-binding protein
      (SREBP), anti-phospho-PRK-1ike ER kinase (p-PERK), anti-phospho-eukaryotic
      initiation factor 2alpha (p-eIF2alpha), and anti-C/EBP homologous protein (CHOP)
      were downregulated compared with the wild-type or mutant HSS-transfected cells.
      Furthermore, PA treatment severely impaired the activity of sarco-endoplasmic
      reticulum Ca(2+)-ATPase (SERCA), leading to imbalanced calcium homeostasis during
      ER stress, which could be rescued in the HSS-trasfected cells. The protection
      provided by HSS to the SERCA is identical to that observed with N-acetyl-l
      cysteine (NAC) and sodium dimercaptopropane sulfonate (Na-DMPS), which are two
      typical free radical scavengers. As a consequence, the rate of ER stress-mediated
      apoptosis in the HSS-expressing cells was significantly reduced. In conclusion,
      the protective effect of HSS against ER stress may be associated with the removal
      of ROS to restore the activity of the SERCA. 

PMID- 24284800
TI  - Designing novel bulk metallic glass composites with a high aluminum content.
AB  - The long-standing challenge for forming Al-based BMGs and their matrix composites
      with a critical size larger than 1 mm have not been answered over the past three
      decades. In this paper, we reported formation of a series of BMG matrix
      composites which contain a high Al content up to 55 at.%. These composites can be
      cast at extraordinarily low cooling rates, compatible with maximum rod diameters
      of over a centimetre in copper mold casting. Our results indicate that proper
      additions of transition element Fe which have a positive heat of mixing with the
      main constituents La and Ce can appreciably improve the formability of the BMG
      matrix composites by suppressing the precipitation of Al(La,Ce) phase resulted
      from occurrence of the phase separation. However, the optimum content of Fe
      addition is strongly dependant on the total amount of the Al content in the Al
      (CoCu)-(La,Ce) alloys.

PMID- 24284797
TI  - Oxidative stress-inducible truncated serine/arginine-rich splicing factor 3
      regulates interleukin-8 production in human colon cancer cells.
AB  - Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SR protein
      family and plays wide-ranging roles in gene expression. The human SRSF3 gene
      generates two alternative splice transcripts, a major mRNA isoform (SRSF3-FL)
      encoding functional full-length protein and a premature termination codon (PTC)
      containing isoform (SRSF3-PTC). The latter is degraded through nonsense-mediated
      mRNA decay (NMD). Treatment of a human colon cancer cell line (HCT116) with 100
      MUM sodium arsenite increased SRSF3-PTC mRNA levels without changing SRSF3-FL
      mRNA levels. A chemiluminescence-based NMD reporter assay system demonstrated
      that arsenite treatment inhibited NMD activity and increased SRSF3-PTC mRNA
      levels in the cytoplasm, facilitating translation of a truncated SRSF3 protein
      (SRSF3-TR) from SRSF3-PTC mRNA. SRSF3-TR lacked two-thirds of the Arg/Ser-rich
      (RS) domain whose phosphorylation state is known to be crucial for subcellular
      distribution. SRSF3-FL was localized in the nucleus, while overexpressed SRSF3-TR
      was diffusely distributed in the cytoplasm and the nucleus. A part of SRSF3-TR
      was also associated with stress granules in the cytoplasm. Interestingly,
      treatment of HCT116 cells with a small interference RNA specifically targeting
      SRSF3-PTC mRNA significantly attenuated arsenite-stimulated induction of c-JUN
      protein, its binding activity to the AP-1 binding site (-126 to 120 bp) in the
      interleukin (IL)-8 gene promoter, and AP-1 promoter activity, resulting in
      significant reduction of arsenite-stimulated IL-8 production. Our results suggest
      that SRSF3-TR may function as a positive regulator of oxidative stress-initiated
      inflammatory responses in colon cancer cells. 

PMID- 24284801
TI  - Anthocyanin-dependent anoxygenic photosynthesis in coloured flower petals?
AB  - Chlorophylless flower petals are known to be composed of non-photosynthetic
      tissues. Here, we show that the light energy storage that can be
      photoacoustically measured in flower petals of Petunia hybrida is approximately
      10-12%. We found that the supposed chlorophylless photosynthesis is an
      anoxygenic, anthocyanin-dependent process occurring in blue flower petals
      (ADAPFP), accompanied by non-respiratory light-dependent oxygen uptake and a 1.5
      fold photoinduced increase in ATP levels. Using a simple, adhesive tape stripping
      technique, we have obtained a backside image of an intact flower petal epidermis,
      revealing sword-shaped ingrowths connecting the cell wall and vacuole, which is
      of interest for the further study of possible vacuole-related photosynthesis.
      Approaches to the interpretations of ADAPFP are discussed, and we conclude that
      these results are not impossible in terms of the known photochemistry of
      anthocyanins. 

PMID- 24284802
TI  - The impact of HIV infection and antiretroviral therapy on the predicted risk of
      Down syndrome.
AB  - OBJECTIVE: The aim of this study was to assess predicted Down syndrome risk,
      based on three serum analytes (triple test), with HIV infection status and
      antiretroviral therapy regimen. METHODS: Screening results in 72 HIV-positive
      women were compared with results from age-matched and race-matched HIV-negative
      controls. Mean concentrations of each analyte were compared by serostatus and
      antiretroviral therapy. Observed Down syndrome incidence in the offspring of HIV
      positive women was calculated from national HIV surveillance data. RESULTS:
      Overall, women with HIV had a significantly higher probability of receiving a
      'high-risk' result than uninfected controls (p = 0.002). Compared with matched
      uninfected controls, women with HIV infection had significantly higher human
      chorionic gonadotrophin, lower unconjugated estriol, and higher overall predicted
      risk of their infant having Down syndrome (1/6250 vs. 1/50 000 p = < 0.001).
      National surveillance data show no evidence of higher than expected incidence of
      Down syndrome in the offspring of HIV-positive women. CONCLUSIONS: HIV infection
      impacts the serum analytes used to assay for Down syndrome risk resulting in a
      high rate of 'high risk' results. However, there is no population-based
      association between maternal HIV infection and Down syndrome. Care should be
      taken when interpreting high-risk serum screening results in HIV-positive women
      to avoid unnecessary invasive diagnostic procedures.

PMID- 24284803
TI  - Segmental grafts in adult and pediatric liver transplantation: improving outcomes
      by minimizing vascular complications.
AB  - IMPORTANCE: The use of technically variant segmental grafts are key in offering
      transplantation to increase organ availability. OBJECTIVE: To describe the use of
      segmental allograft in the current era of donor scarcity, minimizing vascular
      complications using innovative surgical techniques. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective study from August 2007 to August 2012 at a university
      hospital. A total of 218 consecutive liver transplant patients were reviewed, and
      69 patients (31.6%; 38 males and 31 females; mean age, 22.5 years) received
      segmental grafts from living donors or split/reduced-size grafts from deceased
      donors. MAIN OUTCOMES AND MEASURES: Graft type, vascular and biliary
      complications, and patient and graft survival. RESULTS: Of 69 segmental
      transplants, 47 were living donor liver transplants: 13 grafts (27.7%) were right
      lobes, 22 (46.8%) were left lobes, and 12 (25.5%) were left lateral segments.
      Twenty-two patients received deceased donor segmental grafts; of these, 11
      (50.0%) were extended right lobes, 9 (40.9%) were left lateral segments, 1 (4.5%)
      was a right lobe, and 1 (4.5%) was a left lobe. Arterial anastomoses were done
      using 8-0 monofilament sutures in an interrupted fashion for living donor graft
      recipients and for pediatric patients. Most patients received a prophylactic dose
      of low-molecular-weight heparin for a week and aspirin indefinitely. There was no
      incidence of hepatic artery or portal vein thrombosis. Two patients developed
      hepatic artery stenosis and were treated with balloon angioplasty by radiology.
      Graft and patient survivals were 96% and 98%, respectively. CONCLUSIONS AND
      RELEVANCE: Use of segmental allografts is essential to offer timely
      transplantation and decrease waiting list mortality. Living donor liver
      transplants and segmental grafts from deceased donors are complementary. It is
      possible to have excellent outcomes combining a multidisciplinary team approach,
      technical expertise, routine use of anticoagulation, and strict patient and donor
      selection.

PMID- 24284804
TI  - Near-infrared fluorescence amplified organic nanoparticles with aggregation
      induced emission characteristics for in vivo imaging.
AB  - Near-infrared (NIR) fluorescence signals are highly desirable to achieve high
      resolution in biological imaging. To obtain NIR emission with high brightness,
      fluorescent nanoparticles (NPs) are synthesized by co-encapsulation of 2,3-bis(4
      (phenyl(4-(1,2,2-triphenylvinyl)phenylamino)phenyl)fumaronitrile (TPETPAFN), a
      luminogen with aggregation-induced emission (AIE) characteristics, and a NIR
      fluorogen of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (NIR775) using
      1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)
      2000] as the encapsulation matrix. The good spectral overlap between the emission
      of TPETPAFN and the absorption of NIR775 leads to efficient energy transfer,
      resulting in a 47-fold enhancement of the NIR775 emission intensity upon
      excitation of TPETPAFN at 510 nm as compared to that upon direct excitation of
      NIR775 at 760 nm. The obtained fluorescent NPs show sharp NIR emission with a
      band width of 20 nm, a large Stokes shift of 275 nm, good photostability and low
      cytotoxicity. In vivo imaging study reveals that the synthesized NPs are able to
      provide high fluorescence contrast in live animals. The Forster resonance energy
      transfer strategy overcomes the intrinsic limitation of broad emission spectra
      for AIE NPs, which opens new opportunities to synthesize organic NPs with high
      brightness and narrow emission for potential applications in multiplex sensing
      and imaging.

PMID- 24284805
TI  - Does postoperative infection after soft tissue sarcoma resection affect oncologic
      outcomes?
AB  - BACKGROUND AND OBJECTIVES: Prior studies have demonstrated postoperative
      infection may confer a survival benefit after osteosarcoma resection. Our aim was
      to determine whether infection after soft tissue sarcoma resection has similar
      effects on metastasis, recurrence and survival. METHODS: A retrospective review
      was conducted; 396 patients treated surgically for a soft tissue sarcoma between
      2000 and 2008 were identified. Relevant oncologic data were collected. Fifty-six
      patients with a postoperative infection were compared with 340 patients without
      infection. Hazard ratios and overall cumulative risk were evaluated. RESULTS:
      There was no difference in survival, local recurrence or metastasis between
      patients with or without a postoperative infection. Patients were evenly matched
      for age at diagnosis, gender, smoking status, and diabetes status. Tumor
      characteristics did not differ between groups in tumor size, location, depth,
      grade, margin status, stage, and histologic subtype. There was no difference in
      utilization of chemotherapy or radiation therapy between groups. From our
      competing risk model, only positive margin status significantly impacted the risk
      of local recurrence. An increase in tumor size corresponded to an increased risk
      of metastasis and death. CONCLUSIONS: Postoperative infection neither conferred a
      protective effect, nor increased the risk of adverse oncologic outcomes after
      soft tissue sarcoma resection.

PMID- 24284806
TI  - Minimal current intensity to elicit an evoked motor response cannot discern
      between needle-nerve contact and intraneural needle insertion.
AB  - BACKGROUND: The ability of an evoked motor response (EMR) with nerve stimulation
      to detect intraneural needle placement reliably at low current intensity has
      recently been challenged. In this study, we hypothesized that current intensity
      is higher in needle-nerve contact than in intraneural needle placement. METHODS:
      Brachial plexus nerves were exposed surgically in 6 anesthetized pigs. An
      insulated needle connected to a nerve stimulator was placed either with 1 mm
      distance to the nerve (control position), adjacent to nerve epineurium (needle
      nerve contact position), or inside the nerve (intraneural position). Three pulse
      duration settings were applied in random fashion (0.1, 0.3, or 1.0 milliseconds)
      at each needle position. Starting at 0.0 mA, electrical current was increased
      until a minimal threshold current resulting in a specific EMR was observed. Fifty
      threshold current measurements were scheduled for each needle position-pulse
      duration setting. RESULTS: Four hundred-fifty threshold currents in 50 peripheral
      nerves were measured. Threshold current intensities (mA) to elicit EMR showed
      small differences between the needle-nerve contact position [median (25th-75th
      percentiles); 0.1 milliseconds: 0.12 (0.08-0.18) mA; 0.3 milliseconds: 0.10 (0.06
      0.12) mA; 1.0 milliseconds: 0.06 (0.04-0.10) mA] and the intraneural position
      (0.1 milliseconds: 0.12 [0.10-0.16] mA; 0.3 milliseconds: 0.08 [0.06-0.10] mA;
      1.0 milliseconds: 0.06 [0.06-0.08] mA) that are neither statistically significant
      nor clinically relevant. Regardless of the pulse duration that was applied, the
      98.33% confidence interval revealed a difference of at most 0.02 mA. However,
      threshold current intensities to elicit EMR were lower for the needle-nerve
      contact position than for the control position (0.1 milliseconds: 0.28 [0.26
      0.32] mA; 0.3 milliseconds: 0.20 [0.16-0.22] mA; 1.0 milliseconds: 0.12 [0.10
      0.14] mA). CONCLUSIONS: The confidence interval for differences suggests minimal
      current intensity to elicit a motor response that cannot reliably discern between
      a needle-nerve contact from intraneural needle placement. In addition, an EMR at
      threshold currents <0.2 mA (irrespective of the applied pulse duration) indicates
      intraneural needle placement or needle-nerve contact.

PMID- 24284807
TI  - Surface dominant photoresponse of multiferroic BiFeO3 nanowires under sub-bandgap
      illumination.
AB  - A surface dominant sub-bandgap photo-carrier generation has been observed in
      multiferroic BiFeO3 (BFO) nanowires, which is mainly attributed to the
      depopulation of surface states that exist within the bandgap. Mapping of surface
      potential using Kelvin probe force microscopy (KPFM) further supports the
      depopulation of surface states in BFO nanowires under sub-bandgap illumination.
      The mechanism of photovoltage generation in BFO nanowires is investigated by
      measuring the photoresponse with local illumination of visible laser pulses at
      different positions of the BFO nanowires. Interestingly, large photovoltage
      signals were observed when the laser spot was focused close to contact
      electrodes, showing a position dependent effect of photoresponse in the BFO
      nanowires. The sub-bandgap excitation of surface states in multiferroic nanowires
      offers potential new strategies for application in photovoltaic devices. 

PMID- 24284808
TI  - Does the mild traumatic brain injury (mTBI) research need to be internationalized
      right now?

PMID- 24284809
TI  - Obstructive sleep apnea syndrome; a neglected cause of traffic collision among
      Iranian public transport drivers.

PMID- 24284810
TI  - Kinetic energy management in road traffic injury prevention: a call for action.
AB  - By virtue of their variability, mass and speed have important roles in
      transferring energies during a crash incidence (kinetic energy). The sum of
      kinetic energy is important in determining an injury severity and that is equal
      to one half of the vehicle mass multiplied by the square of the vehicle speed. To
      meet the Vision Zero policy (a traffic safety policy) prevention activities
      should be focused on vehicle speed management. Understanding the role of kinetic
      energy will help to develop measures to reduce the generation, distribution, and
      effects of this energy during a road traffic crash. Road traffic injury
      preventive activities necessitate Kinetic energy management to improve road user
      safety.

PMID- 24284811
TI  - Application of mark-recapture to evaluate preventive road traffic injury policy.

PMID- 24284812
TI  - Yubitsume: ritualistic self-amputation of proximal digits among the Yakuza.
AB  - Yubitsume is the ritualistic self-amputation of the proximal digits at the distal
      interphalangeal joint (DIP) among members of the Japanese Mafia, or Yakuza. This
      practice of self-mutilation is done as a sign of apology for making a mistake
      deemed punishable by higher-ranking members or violating the code of the Yakuza.
      Members of the Yakuza may present to emergency departments seeking medical
      assistance to stop hemorrhage or treat infection at the site of injury following
      self-amputation or to have the severed portion of the injured finger reattached.

PMID- 24284813
TI  - Influence of spatial distribution and size of clones on the realized outcrossing
      rate of the marsh cinquefoil (Comarum palustre).
AB  - BACKGROUND AND AIMS: Clonal growth is a common feature in flowering plants. As
      clone size increases, the selfing rate in self-compatible species is likely to
      increase due to more frequent geitono-pollination events (i.e. pollination among
      flowers within the same genet). This study investigated the breeding system of
      the marsh cinquefoil (Comarum palustre) and assessed spatial distribution of
      clones, clone size and architecture, and their effects on realized outcrossing
      rates. In addition, pollen dispersal was investigated in two patchy populations.
      METHODS: The species' breeding system was investigated under controlled
      conditions through hand pollinations (self- vs. cross-pollination). Using
      microsatellite markers, an assessment was made of the realized outcrossing rates
      and the genetic diversity in four natural populations, the clonal structure in
      two populations within five 15 * 15 m sampling plots following 0.5 * 0.5 m grids,
      and the pollen dispersal through paternity assignment tests in those two
      populations. KEY RESULTS: Comarum palustre is a self-compatible species but only
      presents a low rate of spontaneous self-pollination. The occurrence of inbreeding
      depression was not detected at the seed set stage (delta(SS) = 0.04). Clones were
      spatially clumped (A(C) = 0.60-0.80), with intermediate to no intermingling of
      the ramets (D(C) = 0.40-1.00). Genet size ranged from one to 171 ramets. Patchy
      populations had low outcrossing rates (t(m) = 0.33-0.46). Large clones showed
      lower outcrossing rates than small clones. Pollen dispersal mainly occurred
      within patches as only 1-7 % of the pollination events occurred between patches
      of >25 m separation. Seedling recruitment events were detected. CONCLUSIONS:
      Genet size together with distances between patches, through increasing geitono
      pollination events, appeared to be important factors influencing realized
      outcrossing rates. The study also revealed seed flow allowing seedling
      recruitment, which may contribute to increasing the number of new patches, and
      potentially further enhance gene flow within populations.

PMID- 24284814
TI  - Negative effects of temperature and atmospheric depositions on the seed viability
      of common juniper (Juniperus communis).
AB  - BACKGROUND AND AIMS: Environmental change is increasingly impacting ecosystems
      worldwide. However, our knowledge about the interacting effects of various
      drivers of global change on sexual reproduction of plants, one of their key
      mechanisms to cope with change, is limited. This study examines populations of
      poorly regenerating and threatened common juniper (Juniperus communis) to
      determine the influence of four drivers of global change (rising temperatures,
      nitrogen deposition, potentially acidifying deposition and altering precipitation
      patterns) on two key developmental phases during sexual reproduction,
      gametogenesis and fertilization (seed phase two, SP2) and embryo development
      (seed phase three, SP3), and on the ripening time of seeds. METHODS: In 42
      populations throughout the distribution range of common juniper in Europe, 11,943
      seeds of two developmental phases were sampled. Seed viability was determined
      using seed dissection and related to accumulated temperature (expressed as
      growing degree-days), nitrogen and potentially acidifying deposition (nitrogen
      plus sulfur), and precipitation data. KEY RESULTS: Precipitation had no influence
      on the viability of the seeds or on the ripening time. Increasing temperatures
      had a negative impact on the viability of SP2 and SP3 seeds and decreased the
      ripening time. Potentially acidifying depositions negatively influenced SP3 seed
      viability, while enhanced nitrogen deposition led to lower ripening times.
      CONCLUSIONS: Higher temperatures and atmospheric deposition affected SP3 seeds
      more than SP2 seeds. However, this is possibly a delayed effect as juniper seeds
      develop practically independently, due to the absence of vascular communication
      with the parent plant from shortly after fertilization. It is proposed that the
      failure of natural regeneration in many European juniper populations might be
      attributed to climate warming as well as enhanced atmospheric deposition of
      nitrogen and sulfur.

PMID- 24284815
TI  - Effect of root length on epicotyl dormancy release in seeds of Paeonia ludlowii,
      Tibetan peony.
AB  - BACKGROUND AND AIMS: Epicotyl dormancy break in seeds that have deep simple
      epicotyl morphophysiological dormancy (MPD) requires radicle emergence and even a
      certain root length in some species. However, the mechanisms by which root length
      affects epicotyl dormancy break are not clear at present. This study aims to
      explore the relationship between root length and epicotyl dormancy release in
      radicle-emerged seeds of Tibetan peony, Paeonia ludlowii, with discussion of the
      possible mechanisms. METHODS: Radicle-emerged seeds (radicle length 1.5, 3.0, 4.5
      and 6.0 cm) were incubated at 5, 10 and 15  degrees C. During the stratification,
      some seeds were transferred to 15  degrees C and monitored for epicotyl-plumule
      growth. Hormone content was determined by ELISA, and the role of hormones in
      epicotyl dormancy release was tested by exogenous hormone and embryo culture. KEY
      RESULTS: Cold stratification did not break the epicotyl dormancy until the root
      length was >=6 cm. The indole-3-actic acid (IAA) and GA3 contents of seeds having
      6 cm roots were significantly higher than those of seeds with other root lengths,
      but the abscisic acid (ABA) content was lowest among radicle-emerged seeds. GA3
      (400 mg L(-1)) could break epicotyl dormancy of all radicle-emerged seeds, while
      IAA (200 mg L(-1)) had little or no effect. When grown on MS medium, radicles of
      naked embryos grew and cotyledons turned green, but epicotyls did not elongate.
      Naked embryos developed into seedlings on a mixed medium of MS + 100 mg L(-1)
      GA3. CONCLUSIONS: A root length of >=6.0 cm is necessary for epicotyl dormancy
      release by cold stratification. The underlying reason for root length affecting
      epicotyl dormancy release is a difference in the GA3/ABA ratio in the epicotyl
      within radicle-emerged seeds, which is mainly as a result of a difference in ABA
      accumulation before cold stratification.

PMID- 24284816
TI  - Present, past and future of the European rock fern Asplenium fontanum: combining
      distribution modelling and population genetics to study the effect of climate
      change on geographic range and genetic diversity.
AB  - BACKGROUND AND AIMS: Climate change is expected to alter the geographic range of
      many plant species dramatically. Predicting this response will be critical to
      managing the conservation of plant resources and the effects of invasive species.
      The aim of this study was to predict the response of temperate homosporous ferns
      to climate change. METHODS: Genetic diversity and changes in distribution range
      were inferred for the diploid rock fern Asplenium fontanum along a South-North
      transect, extending from its putative last glacial maximum (LGM) refugia in
      southern France towards southern Germany and eastern-central France. This study
      reconciles observations from distribution models and phylogeographic analyses
      derived from plastid and nuclear diversity. KEY RESULTS: Genetic diversity
      distribution and niche modelling propose that genetic diversity accumulates in
      the LGM climate refugium in southern France with the formation of a diversity
      gradient reflecting a slow, post-LGM range expansion towards the current
      distribution range. Evidence supports the fern's preference for outcrossing,
      contradicting the expectation that homosporous ferns would populate new sites by
      single-spore colonization. Prediction of climate and distribution range change
      suggests that a dramatic loss of range and genetic diversity in this fern is
      possible. The observed migration is best described by the phalanx expansion
      model. CONCLUSIONS: The results suggest that homosporous ferns reproducing
      preferentially by outcrossing accumulate genetic diversity primarily in LGM
      climate refugia and may be threatened if these areas disappear due to global
      climate change.

PMID- 24284817
TI  - Natural variation in the genes responsible for maturity loci E1, E2, E3 and E4 in
      soybean.
AB  - BACKGROUND AND AIMS: The timing of flowering has a direct impact on successful
      seed production in plants. Flowering of soybean (Glycine max) is controlled by
      several E loci, and previous studies identified the genes responsible for the
      flowering loci E1, E2, E3 and E4. However, natural variation in these genes has
      not been fully elucidated. The aims of this study were the identification of new
      alleles, establishment of allele diagnoses, examination of allelic combinations
      for adaptability, and analysis of the integrated effect of these loci on
      flowering. METHODS: The sequences of these genes and their flanking regions were
      determined for 39 accessions by primer walking. Systematic discrimination among
      alleles was performed using DNA markers. Genotypes at the E1-E4 loci were
      determined for 63 accessions covering several ecological types using DNA markers
      and sequencing, and flowering times of these accessions at three sowing times
      were recorded. KEY RESULTS: A new allele with an insertion of a long interspersed
      nuclear element (LINE) at the promoter of the E1 locus (e1-re) was identified.
      Insertion and deletion of 36 bases in the eighth intron (E2-in and E2-dl) were
      observed at the E2 locus. Systematic discrimination among the alleles at the E1
      E3 loci was achieved using PCR-based markers. Allelic combinations at the E1-E4
      loci were found to be associated with ecological types, and about 62-66 % of
      variation of flowering time could be attributed to these loci. CONCLUSIONS: The
      study advances understanding of the combined roles of the E1-E4 loci in flowering
      and geographic adaptation, and suggests the existence of unidentified genes for
      flowering in soybean.

PMID- 24284818
TI  - Continuous, high-resolution biospeckle imaging reveals a discrete zone of
      activity at the root apex that responds to contact with obstacles.
AB  - BACKGROUND AND AIMS: Shining a laser onto biological material produces light
      speckles termed biospeckles. Patterns of biospeckle activity reflect changes in
      cell biochemistry, developmental processes and responses to the environment. The
      aim of this work was to develop methods to investigate the biospeckle activity in
      roots and to characterize the distribution of its intensity and response to
      thigmostimuli. METHODS: Biospeckle activity in roots of Zea mays, and also
      Jatropha curcas and Citrus limonia, was imaged live and in situ using a portable
      laser and a digital microscope with a spatial resolution of 10 MUm per pixel and
      the ability to capture images every 0.080 s. A procedure incorporating a Fujii
      algorithm, image restoration using median and Gaussian filters, image
      segmentation using maximum-entropy threshold methods and the extraction of
      features using a tracing algorithm followed by spline fitting were developed to
      obtain quantitative information from images of biospeckle activity. A wavelet
      transform algorithm was used for spectral decomposition of biospeckle activity
      and generalized additive models were used to attribute statistical significance
      to changes in patterns of biospeckle activity. KEY RESULTS: The intensity of
      biospeckle activity was greatest close to the root apex. Higher frequencies (3-6
      Hz) contributed most to the total intensity of biospeckle activity. When a root
      encountered an obstacle, the intensity of biospeckle activity decreased abruptly
      throughout the root system. The response became attenuated with repeated
      thigmostimuli. CONCLUSIONS: The data suggest that at least one component of root
      biospeckle activity resulted from a biological process, which is located in the
      zone of cell division and responds to thigmostimuli. However, neither individual
      cell division events nor root elongation is likely to be responsible for the
      patterns of biospeckle activity.

PMID- 24284819
TI  - Genetic and palaeo-climatic evidence for widespread persistence of the coastal
      tree species Eucalyptus gomphocephala (Myrtaceae) during the Last Glacial
      Maximum.
AB  - BACKGROUND AND AIMS: Few phylogeographic studies have been undertaken of species
      confined to narrow, linear coastal systems where past sea level and
      geomorphological changes may have had a profound effect on species population
      sizes and distributions. In this study, a phylogeographic analysis was conducted
      of Eucalyptus gomphocephala (tuart), a tree species restricted to a 400 * 10 km
      band of coastal sand-plain in south west Australia. Here, there is little known
      about the response of coastal vegetation to glacial/interglacial climate change,
      and a test was made as to whether this species was likely to have persisted
      widely through the Last Glacial Maximum (LGM), or conforms to a post-LGM
      dispersal model of recovery from few refugia. METHODS: The genetic structure over
      the entire range of tuart was assessed using seven nuclear (21 populations; n =
      595) and four chloroplast (24 populations; n = 238) microsatellite markers
      designed for eucalypt species. Correlative palaeodistribution modelling was also
      conducted based on five climatic variables, within two LGM models. KEY RESULTS:
      The chloroplast markers generated six haplotypes, which were strongly
      geographically structured (GST = 0.86 and RST = 0.75). Nuclear microsatellite
      diversity was high (overall mean HE 0.75) and uniformly distributed (FST = 0.05),
      with a strong pattern of isolation by distance (r(2) = 0.362, P = 0.001).
      Distribution models of E. gomphocephala during the LGM showed a wide distribution
      that extended at least 30 km westward from the current distribution to the palaeo
      coastline. CONCLUSIONS: The chloroplast and nuclear data suggest wide persistence
      of E. gomphocephala during the LGM. Palaeodistribution modelling supports the
      conclusions drawn from genetic data and indicates a widespread westward shift of
      E. gomphocephala onto the exposed continental shelf during the LGM. This study
      highlights the importance of the inclusion of complementary, non-genetic data
      (information on geomorphology and palaeoclimate) to interpret phylogeographic
      patterns.

PMID- 24284820
TI  - Both estrogen receptor alpha and beta stimulate pituitary GH gene expression.
AB  - Although sex steroids have been implicated in the control of mammalian growth,
      their direct effect on GH synthesis is less clear. The aim of this study was to
      establish whether estradiol (E2) directly affects GH synthesis in somatotrophs.
      Somatotroph GH3 and MtT/S cells were used as in vitro models. At physiological
      doses of E2 stimulation, GH mRNA levels were increased and the ER antagonist ICI
      182,780 completely abolished this effect. Estrogen receptor (ER) alpha- and
      ERbeta-selective agonists, propylpyrazole triol (PPT), and 2,3-bis(4
      hydroxyphenyl) propionitrile (DPN), respectively, augmented GH mRNA expression
      and secretion, whereas E2 and PPT, but not DPN increased prolactin (PRL) mRNA
      levels. E2, PPT, and DPN stimulated expression of the pituitary transcription
      factor Pou1f1 and increased its binding to the GH promoter. In vivo evidence of
      E2 effects on GH synthesis was obtained from the generation of the somatotroph
      specific ERalpha knockout (sERalpha-KO) mouse model. Basal pituitary GH, PRL,
      POU1F1, and ERalpha mRNA expression levels were lower in sERalpha-KO mice
      compared with those in controls; whereas ERbeta mRNA levels remained unchanged.
      E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control
      and sERalpha-KO ovariectomized mice; however, serum GH levels were unchanged in
      PPT-treated ovariectomized sERalpha-KO mice. In these animal models, PRL mRNA
      levels increased after either E2 or PPT, but an increase was not seen after DPN
      treatment. Thus, we propose a mechanism by which estrogen directly regulates
      somatotroph GH synthesis at a pretranslational level. In contrast to the
      predominant effect of ERalpha in the lactotroph, these results support a role for
      both ERalpha and ERbeta in the transcriptional control of Gh in the somatotroph
      and illustrate important differences in ER isoform specificity in the anterior
      pituitary gland. 

PMID- 24284821
TI  - Vitamin D is a regulator of endothelial nitric oxide synthase and arterial
      stiffness in mice.
AB  - The vitamin D hormone 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential
      for the preservation of serum calcium and phosphate levels but may also be
      important for the regulation of cardiovascular function. Epidemiological data in
      humans have shown that vitamin D insufficiency is associated with hypertension,
      left ventricular hypertrophy, increased arterial stiffness, and endothelial
      dysfunction in normal subjects and in patients with chronic kidney disease and
      type 2 diabetes. However, the pathophysiological mechanisms underlying these
      associations remain largely unexplained. In this study, we aimed to decipher the
      mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac
      function, using mice carrying a mutant, functionally inactive vitamin D receptor
      (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice
      lifelong with the so-called rescue diet enriched with calcium, phosphate, and
      lactose. Here, we report that VDR mutant mice are characterized by lower
      bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of
      the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial
      dysfunction, increased arterial stiffness, increased aortic impedance, structural
      remodeling of the aorta, and impaired systolic and diastolic heart function at
      later ages, independent of changes in the renin-angiotensin system. We further
      demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial
      NO synthase. Our data demonstrate the importance of intact VDR signaling in the
      preservation of vascular function and may provide a mechanistic explanation for
      epidemiological data in humans showing that vitamin D insufficiency is associated
      with hypertension and endothelial dysfunction.

PMID- 24284822
TI  - Minireview: dynamic structures of nuclear hormone receptors: new promises and
      challenges.
AB  - Therapeutic targeting of nuclear receptors (NRs) is presently restricted due to 2
      constraints: 1) a limited knowledge of the structural dynamics of intact receptor
      when complexed to DNA and coregulatory proteins; and 2) the inability to more
      selectively modulate NR actions at specific organ/gene targets. A major obstacle
      has been the current lack of understanding about the function and structure of
      the intrinsically disordered N-terminal domain that contains a major regulatory
      transcriptional activation function (AF1). Current studies of both mechanism of
      action and small molecule-selective receptor modulators for clinical uses target
      the structured pocket of the ligand-binding domain to modulate coregulatory
      protein interactions with the other activation function AF2. However, these
      approaches overlook AF1 activity. Recent studies have shown that highly flexible
      intrinsically disordered regions of transcription factors, including that of the
      N-terminal domain AF1 of NRs, not only are critical for several aspects of NR
      action but also can be exploited as drug targets, thereby opening unique
      opportunities for endocrine-based therapies. In this review article, we discuss
      the role of structural flexibilities in the allosteric modulation of NR activity
      and future perspectives for therapeutic interventions. 

PMID- 24284823
TI  - GATA factors promote ER integrity and beta-cell survival and contribute to type 1
      diabetes risk.
AB  - Pancreatic beta-cell survival remains poorly understood despite decades of
      research. GATA transcription factors broadly regulate embryogenesis and influence
      survival of several cell types, but their role in adult beta-cells remains
      undefined. To investigate the role of GATA factors in adult beta-cells, we
      derived beta-cell-inducible Gata4- and Gata6-knockout mice, along with whole-body
      inducible Gata4 knockouts. beta-Cell Gata4 deletion modestly increased the
      proportion of dying beta-cells in situ with ultrastructural abnormalities
      suggesting endoplasmic reticulum (ER) stress. Notably, glucose homeostasis was
      not grossly altered in Gata4- and Gata6-knockout mice, suggesting that GATA
      factors do not have essential roles in beta-cells. Several ER stress signals were
      up-regulated in Gata4 and Gata6 knockouts, most notably CHOP, a known regulator
      of ER stress-induced apoptosis. However, ER stress signals were not elevated to
      levels observed after acute thapsigargin administration, suggesting that GATA
      deficiency only caused mild ER stress. Simultaneous deletion of Gata4 and CHOP
      partially restored beta-cell survival. In contrast, whole-body inducible Gata4
      knockouts displayed no evidence of ER stress in other GATA4-enriched tissues,
      such as heart. Indeed, distinct GATA transcriptional targets were differentially
      expressed in islets compared with heart. Such beta-cell-specific findings
      prompted study of a large meta-analysis dataset to investigate single nucleotide
      polymorphisms harbored within the human GATA4 locus, revealing several variants
      significantly associated with type 1 diabetes mellitus. We conclude that GATA
      factors have important but nonessential roles to promote ER integrity and beta
      cell survival in a tissue-specific manner and that GATA factors likely contribute
      to type 1 diabetes mellitus pathogenesis. 

PMID- 24284824
TI  - Dynamic postnatal developmental and sex-specific neuroendocrine effects of
      prenatal polychlorinated biphenyls in rats.
AB  - Gestational exposures to estrogenic compounds, both endogenous hormones and
      exogenous endocrine-disrupting chemicals (EDCs), have long-term effects on
      reproductive physiology and behavior. We tested the hypothesis that prenatal
      treatment of rats with low doses of Aroclor 1221 (A1221), a weakly estrogenic
      polychlorinated biphenyl mix previously used in industry, or estradiol benzoate
      (EB), alters development of the hypothalamus in a sexually dimorphic manner and
      subsequently perturbs reproductive function. Pregnant Sprague-Dawley rats were
      injected on embryonic days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1
      mg/kg), or EB (50 MUg/kg). Developmental milestones were monitored, and on
      postnatal days 15, 30, 45, and 90, 1 male and 1 female per litter were
      euthanized. Because of their key roles in the mediation of steroid actions on
      reproductive function, the anteroventral periventricular nucleus (AVPV) and the
      arcuate nucleus (ARC) were punched for a low-density quantitative PCR array of 48
      neuroendocrine genes and analysis of DNA methylation of a subset of genes.
      Gestational exposure to A1221 or EB delayed the timing of puberty in males and
      disrupted estrous cyclicity in females. In the AVPV, 28 genes were affected by
      treatment in a developmental stage-specific manner, mostly in females, which
      exhibited a masculinized expression profile. This included 2 clock genes, Per2
      and Arntl, implicating circadian circuits as being vulnerable to endocrine
      disruption. DNA methylation analysis of 2 genes, Per2 and Ar, showed no effect of
      EDCs and suggested alternative mechanisms for the altered mRNA levels. In the
      ARC, 12 genes were affected by treatment, mostly in males, again with dynamic
      developmental changes. Bionetwork analysis of relationships among genes,
      hormones, and physiological markers showed sexually dimorphic effects of
      estrogenic EDC exposures, with the female AVPV and the male ARC being most
      vulnerable, and provided novel relationships among hypothalamic genes and
      postnatal reproductive maturation. 

PMID- 24284825
TI  - Pyroglutamylated RF-amide peptide (QRFP) gene is regulated by metabolic
      endotoxemia.
AB  - Pyroglutamylated RF-amide peptide (QRFP) is involved in the regulation of food
      intake, thermogenesis, adipogenesis, and lipolysis. The expression of QRFP in
      adipose tissue is reduced in diet-induced obesity, a mouse model in which plasma
      concentrations of endotoxins are slightly elevated. The present study
      investigated the role of metabolic endotoxemia (ME) on QRFP gene regulation. Our
      results uncovered the expression of QRFP in murine macrophages and cell lines.
      This expression has been found to be decreased in mice with ME. Low doses of
      lipopolysaccharide (LPS) transiently down-regulated QRFP by 59% in RAW264.7
      macrophages but not in 3T3-L1 adipocytes. The effect of LPS on QRFP expression in
      macrophages was dependent on the inhibitor of kB kinase and TIR-domain-containing
      adapter-inducing interferon (IFN)-beta (TRIF) but not myeloid differentiation
      primary response gene 88. IFN-beta was induced by ME in macrophages. IFN-beta
      sustainably reduced QRFP expression in macrophages (64%) and adipocytes (49%).
      IFN-gamma down-regulated QRFP (74%) in macrophages only. Both IFNs inhibited QRFP
      secretion from macrophages. LPS-stimulated macrophage-conditioned medium reduced
      QRFP expression in adipocytes, an effect blocked by IFN-beta neutralizing
      antibody. The effect of IFN-beta on QRFP expression was dependent on
      phosphoinositide 3-kinase, p38 MAPK, and histone deacetylases. The effect of IFN
      gamma was dependent on MAPK/ERK kinase 1/2 and histone deacetylases. Macrophage
      conditioned medium containing increased amounts of QRFP preserved adipogenesis in
      adipocytes. In conclusion, LPS induces IFN-beta release from macrophages, which
      reduces QRFP expression in both macrophages and adipocytes in an
      autocrine/paracrine-dependent manner, suggesting QRFP as a potential biomarker in
      ME.

PMID- 24284826
TI  - Clostridium perfringens epsilon toxin: a malevolent molecule for animals and man?
AB  - Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple
      diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein
      produced by Clostridium perfringens (types B and D) that induces fatal enteric
      disease of goats, sheep and cattle. Epsilon toxin (Etx) belongs to the aerolysin
      like toxin family. It contains three distinct domains, is proteolytically
      activated and forms oligomeric pores on cell surfaces via a lipid raft-associated
      protein(s). Vaccination controls Etx-induced disease in the field. However,
      therapeutic measures are currently lacking. This review initially introduces C.
      perfringens toxins, subsequently focusing upon the Etx and its biochemistry,
      disease characteristics in various animals that include laboratory models (in
      vitro and in vivo), and finally control mechanisms (vaccines and therapeutics). 

PMID- 24284827
TI  - Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) induces
      apoptosis in LNCaP prostate cancer cells.
AB  - Prostate cancer is the most common malignancy, accounting for about 25% of all
      incident cases among men in industrialized countries. The human androgen
      dependent prostate cancer cell line LNCaP, which is derived from a metastatic
      lesion of human prostatic adenocarcinoma, is frequently used to study prostate
      cancer associated signaling pathways in vitro. Recently it was described that Rho
      GTPase activation in these cells leads to apoptotic responses. We used the
      bacterial toxins CNFy and CNF1, which specifically and directly activate Rho
      GTPases by deamidation of a single glutamine. We asked whether these Rho
      activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA
      activation, induced by CNFy, does lead to intrinsic apoptosis of the cells.
      Analysis of the underlying signaling pathway reveals that apoptosis induction
      requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic
      pathway previously identified in cancer stem cells. 

PMID- 24284828
TI  - Correlation of ATP citrate lyase and acetyl CoA levels with trichothecene
      production in Fusarium graminearum.
AB  - The correlation of ATP citrate lyase (ACL) and acetyl CoA levels with
      trichothecene production in Fusarium graminearum was investigated using an
      inhibitor (precocene II) and an enhancer (cobalt chloride) of trichothecene
      production by changing carbon sources in liquid medium. When precocene II (30 uM)
      was added to inhibit trichothecene production in a trichothecene high-production
      medium containing sucrose, ACL expression was reduced and ACL mRNA level as well
      as acetyl CoA amount in the fungal cells were reduced to the levels observed in a
      trichothecene trace-production medium containing glucose or fructose. The ACL
      mRNA level was greatly increased by addition of cobalt chloride in the
      trichothecene high-production medium, but not in the trichothecene trace
      production medium. Levels were reduced to those level in the trichothecene trace
      production medium by addition of precocene II (300 uM) together with cobalt
      chloride. These results suggest that ACL expression is activated in the presence
      of sucrose and that acetyl CoA produced by the increased ALC level may be used
      for trichothecene production in the fungus. These findings also suggest that
      sucrose is important for the action of cobalt chloride in activating
      trichothecene production and that precocene II may affect a step down-stream of
      the target of cobalt chloride. 

PMID- 24284829
TI  - Cytotoxic necrotizing factor 1 contributes to Escherichia coli meningitis.
AB  - E. coli is the most common Gram-negative bacteria causing neonatal meningitis,
      and E. coli meningitis continues to be an important cause of mortality and
      morbidity throughout the world. Recent reports of E. coli meningitis caused by
      antimicrobial resistant strains are a particular concern. These findings indicate
      that a novel strategy is needed to identify new targets for prevention and
      therapy of E. coli meningitis. Cytotoxic necrotizing factor 1 (CNF1) is a
      bacterial virulence factor associated principally with E. coli strains causing
      urinary tract infection and meningitis. We have shown that CNF1 contributes to E.
      coli invasion of the blood-brain barrier and penetration into the brain, the
      essential step in the development of E. coli meningitis, and identified the host
      receptor for CNF1, 37-kDa laminin receptor precursor (37LRP). CNF1, however, is a
      cytoplasmic protein and its contribution to E. coli invasion of the blood-brain
      barrier requires its secretion from the bacterial cytoplasm. No signal peptide is
      found in the CNF1 sequence. CNF1 secretion is, therefore, a strategy utilized by
      meningitis-causing E. coli to invade the blood-brain barrier. Elucidation of the
      mechanisms involved in CNF1 secretion, as shown in this report with the
      involvement of Fdx and YgfZ provides the novel information on potential targets
      for prevention and therapy of E. coli meningitis by virtue of targeting the
      secretion of CNF1. 

PMID- 24284830
TI  - The expression of type-1 and type-2 nitric oxide synthase in selected tissues of
      the gastrointestinal tract during mixed mycotoxicosis.
AB  - The aim of the study was to verify the hypothesis that intoxication with low
      doses of mycotoxins leads to changes in the mRNA expression levels of nitric
      oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the
      gastrointestinal tract and the liver. The experiment involved four groups of
      immature gilts (with body weight of up to 25 kg) which were orally administered
      zearalenone in a daily dose of 40 MUg/kg BW (group Z, n = 18), deoxynivalenol at
      12 MUg/kg BW (group D, n = 18), zearalenone and deoxynivalenol (group M, n = 18)
      or placebo (group C, n = 21) over a period of 42 days. The lowest mRNA expression
      levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes were noted in
      the sixth week of the study, in particular in group M. Our results suggest that
      the presence of low mycotoxin doses in feed slows down the mRNA expression of
      both nitric oxide synthase isomers, which probably lowers the concentrations of
      nitric oxide, a common precursor of inflammation. 

PMID- 24284831
TI  - Impact of stereotactic body radiotherapy on colorectal cancer with distant
      metastases.
AB  - Stereotactic radiotherapy is a minimally invasive technique for delivering highly
      focused ionizing radiation with extreme precision. This technique was initially
      developed in neurosurgical practice and applied to extracranial lesions in the
      1990s, and was termed stereotactic body radiotherapy (SBRT). Studies have
      reported that the resection of distant metastases from colorectal cancer (CRC)
      contributes to relatively long-term survival. However, the resection of pulmonary
      and liver metastases is not possible for various reasons. SBRT offers a
      therapeutic alternative to unresectable metastatic lesions. The present study
      describes three cases of distant metastasis from CRC that exhibited a complete
      response (CR) to SBRT. Case 1 is a 70-year-old man with recurrent liver
      metastases after surgery for rectal cancer with liver metastasis (S3: diameter
      1.8 cm and volume 3.0 ml; S6: diameter 1.3 cm and volume 1.2 ml). Cases 2 and 3
      were 65-year-old and 70-year-old men, respectively. Both patients had pulmonary
      metastasis after surgery for rectal and cecum cancer (Case 2: diameter 1.2 cm and
      volume 0.9 ml; Case 3: diameter 0.8 cm and volume 0.27 ml). All cases were
      moderately differentiated adenocarcinomas. No serious adverse side-effects were
      observed during the therapy. CR was obtained in all patients on the basis of
      computed tomography 15-33 months after radiotherapy. Our experience supports that
      SBRT is a safe and alternative technique for resection in patients with distant
      metastasis from CRC who have small metastatic tumor volume.

PMID- 24284832
TI  - Cognitive factors correlating with the metacognition of the phenomenal properties
      of experience.
AB  - The awareness of the phenomenal qualities of one's experiences can be considered
      as an instance of metacognition. Although some people take qualia (sensory
      qualities such as the redness of red) as salient features of phenomenal
      experience, others have expressed views that doubt or deny the central importance
      of qualia. How do such cognitive heterogeneities occur? What parameters influence
      them? Here I examine the relationship between the awareness of the phenomenal
      qualities of subjective experience (qualia and free will) and general cognitive
      tendencies. The awareness of qualia was found to be more varied among subjects
      compared to the belief in free will. Various cognitive tendencies correlated with
      the metacognition of phenomenal experience. The awareness of qualia was found to
      increase significantly with age, suggesting a continuous learning process. These
      results suggest that heterogeneities in the metacognition of phenomenal
      properties of experience are important constraints in human cognition. 

PMID- 24284834
TI  - Separation of CO2-N2 mixtures in 3D carbon-based porous nanotube networks: a
      molecular dynamics investigation.
AB  - The separation of an equimolar CO2-N2 mixture in a 3D porous carbon nanotube
      network has been investigated. An enhanced CO2 adsorption selectivity has been
      observed. The diffusion coefficients of the adsorbed molecules have been related
      to their residence dynamics in the vicinity of the carbon atoms of the nanopore. 

PMID- 24284833
TI  - Semisynthetic model calibration for monitoring glucose in mammalian cell culture
      with in situ near infrared spectroscopy.
AB  - Near infrared (NIR) spectroscopy has the capability of providing real-time, multi
      analyte monitoring of the complex reaction mixture associated with cell culture
      processes. However, the development of robust models to predict the concentration
      of key analytes has proven difficult. In this study, a modeling methodology using
      semisynthetic process samples was used to predict glucose concentrations in
      Chinese Hamster Ovary (CHO) cell culture processes. Partial Least Squares (PLS)
      regression models were built from in situ NIR spectra, and glucose levels between
      4.0 and 14.0 g/L. Two models were constructed. The "standard model" used data
      provided by cell culture production process samples. The "full model" included
      the data provided from both cell culture production process samples and
      semisynthetic samples. The semisynthetic samples were generated by titrating cell
      culture samples with target viable cell density (VCD) and lactate levels to
      defined glucose concentrations. The robustness of each model was gauged by
      predicting glucose in a subsequent cell culture process utilizing a media
      formulation and cell line not contained in the calibration data sets. The "full
      model" generated glucose predictions with a root mean square error of prediction
      (RMSEP) of 0.99 g/L while the "standard model" provided glucose predictions with
      a RMSEP of 2.26 g/L. The modeling approach utilizing semisynthetic samples proved
      to be faster development and more effective than using just standard cell culture
      processes.

PMID- 24284835
TI  - Differences in cytoplasmic maturation between the BCB+ and control porcine
      oocytes do not justify application of the BCB test for a standard IVM protocol.
AB  - The Brilliant Cresyl Blue (BCB) test relies on G6PDH activity and a simple
      protocol for the selection of higher quality oocytes. Although the BCB+ oocytes
      of all the species that have been investigated are characterized by superior
      quality when compared to BCB- counterparts, application of the test for embryo
      production still remains an open issue. The aim of our study was to compare BCB+
      and the control oocytes (not subjected to the BCB test) in terms of selected
      aspects of cytoplasmic maturation (mtDNA copy number, mitochondria distribution,
      relative transcript abundance of six marker genes). The results of our study
      revealed more relevant differences within the BCB+ and the control oocytes
      (before and after IVM) than between the two categories of oocytes. There was no
      difference in the transcript abundance of the BCB+ and the control oocytes in 5
      out of 6 analyzed genes (BMP15, GDF9, ATP5A1, EEF1A, ZAR1) and in mtDNA content
      (pre-IVM 179609 vs. 176595 and post-IVM 187243 vs. 246984, respectively). With
      regard to mitochondria distribution in pre- and post-IVM oocytes, there was
      nonsignificant tendency for a more frequent occurrence of the expected patterns
      in the BCB+ group. The results of the present study do not support the
      application of BCB staining in a routine IVM protocol due to relatively high
      similarity in selected parameters characterizing cytoplasmic maturation of BCB+
      and control oocytes. This high similarity may results from the limited amount of
      less competent BCB- oocytes (10%) still present among nonselected oocytes of
      proper morphology. 

PMID- 24284836
TI  - Long-term postinjury functional recovery: outcomes of geriatric consultation.
AB  - IMPORTANCE: Functional recovery is an important outcome following injury.
      Functional impairment is persistent in the year following injury for older trauma
      patients. OBJECTIVE: To measure the impact of routine geriatric consultation on
      functional outcomes in older trauma patients. DESIGN, SETTING, AND PARTICIPANTS:
      In this pretest-posttest study, the pretest control group (n = 37) was
      retrospectively identified (December 2006-November 2007). The posttest geriatric
      consultation (GC) group (n = 85) was prospectively enrolled (December 2007-June
      2010). We then followed up both groups for 1 year after enrollment. This study
      was conducted at an academic level 1 trauma center with adults 65 years of age
      and older admitted as an activated code trauma. INTERVENTION: Routine GC. MAIN
      OUTCOMES AND MEASURES: The Short Functional Status survey of 5 activities of
      daily living (ADLs) at hospital admission and 3, 6, and 12 months postinjury.
      RESULTS: The unadjusted Short Functional Status score (GC group only) declined
      from 4.6 preinjury to 3.7 at 12 months postinjury, a decline of nearly 1 full ADL
      (P < .05). The ability to shop for personal items was the specific ADL more
      commonly retained by the GC group compared with the control group. The GC group
      had a better recovery of function in the year following injury than the GC group,
      controlling for age, sex, race/ethnicity, length of stay, comorbidity, injury
      severity, postdischarge rehabilitation, complication, and whether surgery was
      performed (P < .01), a difference of 0.67 ADL abilities retained by the GC group
      compared with the control group (95% CI, 0.06-1.4). CONCLUSIONS AND RELEVANCE:
      Functional recovery for older adults following injury may be improved by GC.
      Early introduction of multidisciplinary care in geriatric trauma patients
      warrants further investigation.

PMID- 24284837
TI  - Polymer-directed synthesis of metal oxide-containing nanomaterials for
      electrochemical energy storage.
AB  - Metal oxide-containing nanomaterials (MOCNMs) of controllable structures at the
      nano-scale have attracted considerable interest because of their great potential
      applications in electrochemical energy storage devices, such as lithium-ion
      batteries (LIBs) and supercapacitors. Among many structure-directing agents,
      polymers and macromolecules, including block copolymers (BCPs) and graphene,
      exhibit distinct advantages in the template-assisted synthesis of MOCNMs. In this
      feature article, we introduce the controlled preparation of MOCNMs employing BCPs
      and graphene as structure-directing agents. Typical synthetic strategies are
      presented for the control of structures and sizes as well as the improvement of
      physical properties and electrochemical performance of MOCNMs in LIBs and
      supercapacitors. 

PMID- 24284838
TI  - Antioxidant therapy for pain relief in patients with chronic pancreatitis:
      systematic review and meta-analysis.
AB  - BACKGROUND: Currently, there is no specific therapy for chronic pancreatitis
      (CP). The treatment of micronutrient antioxidant therapy for painful CP has been
      sporadically used for more than 30 years, however, its efficacy are still poorly
      understood. OBJECTIVE: The purpose of this meta-analysis is to investigate the
      safety and efficacy of antioxidant therapy for pain relief in patients with CP.
      SETTING: University Hospital in China STUDY DESIGN: Systematic review and meta
      analysis METHODS: Two authors independently reviewed the search results and
      extracted data and disagreements were resolved by discussion. Effects were
      summarized using standardized mean differences (SMDs), weighted mean differences,
      or odds ratio (OR) according to the suitable effect model. MEDLINE, PsycINFO,
      Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials  were
      searched from 1980 through December 2012. Randomized controlled trials (RCTs)
      that studied antioxidant supplementation for pain relief in patients with CP were
      analyzed. RESULTS: Nine randomized controlled trials (RCTs) involving 390
      patients were included. Overall, there was no association of antioxidant therapy
      with pain reduction in CP patients (SMD, -0.55; 95% CI, -1.22 to 0.12; P = 0.67).
      However, antioxidant therapy significantly increased blood levels of antioxidants
      in CP patients versus the placebo group (SMD, 1.08; 95% CI, 0.74 to 1.43; P <
      0.00001). Interestingly, combined antioxidant (selenium, beta-carotene, vitamin
      C, vitamin E, methionine) therapy was found to be associated with pain relief
      (SMD, -0.93; 95% CI, -1.72 to -0.14; P = 0.02), while the trials in which a
      single antioxidant was used revealed no significant pain relief (SMD, -0.12; 95%
      CI, -1.23 to 0.99; P = 0.83) in CP patients. Strong evidence was obtained that
      the antioxidants increased adverse effects (OR, 6.09; 95% CI, 2.29 to 16.17, P <
      0.01); nevertheless, none was serious. LIMITATIONS: Because of the small sample,
      a consolidated conclusion cannot be reached based on current RCTs. Large-sample
      RCTs are needed to clarify the analgesic effect of antioxidants in CP patients.
      CONCLUSIONS: Combined antioxidant therapy seems to be a safe and effective
      therapy for pain relief in CP patients. Measures of total antioxidant status may
      not help to monitor the efficacy of antioxidant therapy for patients with CP.

PMID- 24284839
TI  - Antinociceptive effect of prostatic acid phosphatase in a rat model of cancer
      induced bone pain.
AB  - BACKGROUND: Cancer-induced bone pain (CIBP) is a severe chronic pain that is less
      than adequately controlled by conventional analgesics. Prostatic acid phosphatase
      (PAP) has been considered as a diagnostic marker for prostate cancer and its
      transmembrane isoform has been reported to play an antinociceptive effect in
      neuropathic and inflammatory pain. However, it remains unknown whether it has an
      analgesic effect on CIBP and what are the underlying mechanisms. OBJECTIVE: In
      the present study, we tested whether PAP could alleviate the pain symptoms
      induced by bone cancer in a rat model. STUDY DESIGN: A randomized, double blind,
      and controlled rat animal trial. METHODS: We first established a rat CIBP model
      and observed the spinal expression of PAP by immunofluorescence histochemistry
      and Western blot. Then, PAP (0.1, 0.3, or 1 MUg) was intrathecally administered
      in the CIBP rats in a repeated manner from 15 to 18 days (once per day) after
      inoculation of tumor cells. On postoperative day (POD) 18, the mechanical paw
      withdrawal threshold was tested for checking the dose-effect curve and ED50 of
      the antinociceptive effect of PAP. In an another test, a single dose of ED50 of
      PAP was intrathecally injected on POD 15 to observe the time course of its
      effect. Furthermore, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (3 mg/kg), an
      adenosine A1 receptor antagonist, or dipyridamole (DIP) (10 MUg), a nucleoside
      transporter inhibitor, was administered to the CIBP rats for exploring the
      analgesic mechanisms of PAP. The concentration of extracellular adenosine was
      also detected by microdialysis method after intrathecal injection of PAP (0.57
      MUg) and DIP (10 MUg) in the CIBP rats. Finally, an in vivo electrophysiological
      study of the CIBP rats was performed to observe whether the electrically evoked
      response of spinal wide-dynamic-range (WDR) neurons could be affected by PAP
      (0.57 MUg), DIP (10 MUg), or DPCPX (10 MUg). RESULTS: The expression of PAP in
      the spinal dorsal horn was significantly reduced in the CIBP rats, and
      intrathecal injection of PAP dose-dependently attenuated CIBP-induced mechanical
      allodynia via the adenosine A1 receptor. Simultaneously, intrathecal injection of
      PAP increased the extracellular concentration of spinal adenosine in the CIBP
      rats, as well as inhibited the neuronal responses of WDR neurons in deep layers
      within the spinal dorsal horn through the adenosine A1 receptor. Finally, the
      analgesic effect of PAP was potentiated by DIP, the nucleoside transporter
      inhibitor. LIMITATIONS: It's not clear whether PAP's antinociceptive effect is
      mediated by other signaling molecules besides the adenosine A1 receptor. In
      addition, the long-term antinociceptive effect of intrathecal PAP is still not
      clear. CONCLUSIONS: Our study demonstrated that PAP was involved in the
      maintenance of CIBP and could effectively suppress central sensitization by
      increasing spinal extracellular adenosine concentrations to exert a significant
      antinociceptive effect via the adenosine A1 receptor in CIBP rats. Therefore, our
      experiments suggest that the endogenous enzyme PAP may be a promising candidate
      for CIBP treatment.

PMID- 24284840
TI  - Percutaneous endoscopic lumbar discectomy for L5-S1 disc herniation:
      transforaminal versus interlaminar approach.
AB  - BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is a minimally
      invasive spinal technique. The unique anatomic features of the L5-S1 space
      include a large facet joint, narrow foramen, small disc space, and a wide
      interlaminar space. PELD can be performed via 2 routes, transforaminal (TF-PELD)
      or interlaminar (IL-PELD). However, it is questionable that the decision of the
      endoscopic route for L5-S1 discs only depends on the surgeon's preference and
      anatomic relation between iliac bone and disc space. Thus far, no study has
      compared TF-PELD with IL-PELD for L5-S1 disc herniation. OBJECTIVE: The goal of
      this study was to compare the radiologic features and results of TF-PELD and IL
      PELD. We have clarified the patient selection for the PELD route for L5-S1 disc
      herniation. STUDY DESIGN: Retrospective evaluation. METHODS: Thirty consecutive
      patients each were treated with TF-PELD and IL-PELD for L5-S1 disc herniation in
      2 institutes, respectively. Radiological assessments were performed pre- and
      postoperatively. The disc type, disc size, location, migration, disc height,
      foraminal height, iliolumbar angle, iliac height, and interlaminar space were
      analyzed. Clinical data were compared with a 2-year follow-up period. Pre- and
      postoperative pain was measured using a visual analog scale (VAS; 0 - 10) and
      functional status was assessed using the Oswestry Disability Index (ODI; 0 -
      100%) and the time to return to work. RESULTS: In the 2 groups, the mean VAS
      scores for back and leg pain, as well as the ODI, were significantly improved.
      The mean time to return to work was 4.9 weeks with TF-PELD and 4.4 weeks with IL
      PELD. Incomplete removal, resulting in the need for subsequent open surgery,
      occurred in one case (3.3%) of TF-PELD and in 2 cases (6.6%) of IL-PELD.
      Postoperative dysesthesia developed in 2 patients (6.7%) after IL-PELD; however,
      there was no dysesthesia after TF-PELD. Recurrence occurred in 3.3% with TF-PELD
      and in 6.7% with IL-PELD during the 2-year follow-up. A significant difference
      between groups was demonstrated in terms of disc type, location, and migration.
      The prevalence of axillary disc herniation (20 cases, 66.7%) was higher than that
      of shoulder disc herniation (10 cases, 33.3%) in the IL-PELD group. On the other
      hand, in the TF-PELD group, shoulder disc herniation (20 cases, 66.7%) was more
      prevalent than the axillary type (10 cases, 33.3%; P = 0.01). A higher number of
      patients in the TF-PELD group had central disc herniation (10 cases, 33.3%)
      compared with that in the IL-PELD group (2 cases, 6.7%; P = 0.01). Eleven cases
      (36.7%) of high grade migration were removed using IL-PELD and one case (6.7%)
      was removed using TF-PELD (P = 0.01). TF-PELD was used to remov only 3 cases of
      recurrent disc herniation. There were no significant differences of radiologic
      parameters between the iliac bone and L5-S1 disc space between the 2 groups.
      LIMITATIONS: This study has a relatively small sample size and a short follow-up
      period. CONCLUSION: This study demonstrated that TF-PELD is preferred for
      shoulder type, centrally located, and recurrent disc herniation, while IL-PELD is
      preferred for axillary type and migrated discs, especially those of a high grade.

PMID- 24284841
TI  - Effects of two different doses of epidural steroid on blood glucose levels and
      pain control in patients with diabetes mellitus.
AB  - BACKGROUND: A high incidence of diabetes mellitus has been reported among
      patients diagnosed with lumbar degenerative spinal diseases. Although epidural
      steroid injections are known to increase the postprocedure blood glucose level,
      it has not been investigated whether a lower steroid dose can reduce blood
      glucose excursions and still be effective in controlling patients' subjective
      pain. OBJECTIVE: We compared the effects of 2 common doses of triamcinolone
      administered via epidural steroid injections on blood glucose levels and pain
      control in patients with diabetes mellitus to determine an adequate epidural
      steroid dose. STUDY DESIGN: A prospective observational study. METHODS: One
      hundred patients with diabetes mellitus were enrolled. They received lumbar
      transforaminal, lumbar interlaminar, or caudal epidural triamcinolone for
      radiculopathy, spinal stenosis, or failed back surgery syndrome. After the type
      of procedure was clinically determined, the doses of triamcinolone given were
      randomly chosen, either 40 mg (Group 40) or 20 mg (Group 20). The patients were
      asked to measure their finger stick blood glucose level twice daily (fasting and
      postprandial) for 3 days before the injection, on the day of the injection, for 7
      days after the injection, and at 14 days after the injection. They also kept a
      blood glucose diary. Employment status and clinical outcome were evaluated at 8
      weeks after the procedure. RESULTS: There were significant increases in fasting
      blood glucose (FBG) level on postprocedure day (PPD) #1 to PPD #3 in Group 40,
      but on PPD #1 in Group 20. Moreover, there was a significant difference in FBG
      between groups on PPD #1 and PPD #2 (FBG on PPD #1: 179 [51]) mg/dL in Group 40
      versus 146 [50] mg/dL in Group 20, P < 0.001]. Postprandial blood glucose (PBG)
      level was significantly elevated in both groups from PPD #0 to PPD #3. Notably,
      the increase in PBG was significantly greater in Group 40 than Group 20 on PPD #0
      and #1 (PBG on PPD #0: 288 [57] mg/dL versus 242 [94] mg/dL in Groups 40 and 20,
      respectively, P = 0.004). The numeric rating scale for pain reported by the
      patients decreased for 2 weeks after treatment with no difference between groups.
      Employment status and clinical outcome was not different between groups.
      LIMITATIONS: The patients who chose to participate in this study may be a cohort
      of well-controlled patients with diabetes mellitus. The type of procedure
      performed was determined by a clinical decision and not randomized. The different
      routes of administration and diagnosis of failed back surgery syndrome can result
      in different levels of systemic absorption, thereby influencing the degree and
      duration of hyperglycemia. In patients with FBSS, the epidural space may be
      destructed by surgery and adhesive changes in epidural space could be extensive.
      Therefore, we thought that the absorption of epidural space in these patients
      would be incomplete or slow compared with those without FBSS. CONCLUSION:
      Epidural steroid injections were associated with statistically significant
      elevations in PBG in patients with diabetes for up to 4 days after the procedure.
      The higher dose of triamcinolone increased FBG and PBG greater than a lower dose
      did without affecting pain control, employment status, or clinical outcome. Thus,
      with respect to glucose and pain control, 20 mg of triamcinolone appears to be
      recommended rather than 40 mg in patients with diabetes. Clinical Trials
      registration : NCT01435707.

PMID- 24284842
TI  - Assessment of neuropathic pain in patients with cancer: the interobserver
      reliability. An observational study in daily practice.
AB  - BACKGROUND: Neuropathic pain (NeP) is a burdensome problem in all stages of
      cancer. Although clinical judgment is accepted as a surrogate for an objective
      gold standard in diagnosing NeP, no publications were found about its
      reliability. OBJECTIVES: Therefore, levels of agreement on the clinical
      examination of NeP were estimated by calculating kappa-value (K) and percentage
      of pair wise agreement (PA) to determine the interobserver reliability of
      diagnosing NeP. SETTING: The outpatient clinic of medical oncology of the Radboud
      University Nijmegen Medical Centre. METHODS: Patients with cancer with potential
      NeP complaints were recruited from the outpatient clinic of medical oncology.
      Physicians were recruited from the department of pain and palliative medicine.
      Physicians and patients were recruited for participation in an observational
      study in daily practice. Each patient (N = 34) was examined by 2 specialists via
      independent clinical assessment. All consultations were video recorded.  After
      each assessment, physicians were asked to indicate the most adequate
      characterization of the pain: pure NeP, pure nociceptive pain (NoP), mixed pain
      (MiP), or no pain (NP). RESULTS: Kappa (K) for the diagnosis of the most adequate
      pain characterization was 0.50, PA 64.7%. For diagnosing pure NeP k was 0.78 (PA
      91.2%), for the NeP component (NeP + MiP)  and NoP component (NoP + MiP), it was
      respectively 0.52 (PA  76.5%) and 0.61 (PA 82.4%). For the diagnosis on the basis
      of the grading system between physicians, K was 0.34 (PA 52.9%). The intrarater
      reliability for the diagnosis of an NeP component on the basis of clinical
      assessment and the NeP component on the basis of the grading system, for pain
      specialists K was 0.69 (PA 85.3%) and for palliative care specialists K was 0.61
      (PA 79.4%). LIMITATIONS: The values of K and the PA for the existence of an NeP
      component are not satisfying and the clinical agreement between physicians around
      findings from physical examination should encourage a better standardization of
      the clinical assessment and classification of pain in patients with cancer in
      respect with the identification of NeP.  CONCLUSIONS: A substantial level of
      agreement was found for the diagnosis of pure NeP and a moderate level of
      agreement for the diagnosis of the NeP component was found, both with a PA = 70%.
      There was only a fair agreement between the physicians regarding the grading
      system. However, there was a substantial level of (interrater) agreement for the
      diagnosis of an NeP component and the outcome of the grading system. The findings
      in this study also suggest that a better standardization of the clinical
      assessment and classification of pain in patients with cancer with respect to the
      identification of neuropathic pain is necessary.

PMID- 24284843
TI  - Objective sensory evaluation of the spread of complex regional pain syndrome.
AB  - BACKGROUND: The spread of complex regional pain syndrome (CRPS) has been well
      documented. Many severe refractory long-standing patients have total body pain
      (TBP) that evolved from a single extremity injury. OBJECTIVE: The purpose of this
      study was to document by objective sensory threshold testing the extent of body
      area involvement in 20 long-standing patients with CRPS who have TBP. STUDY
      DESIGN: A comparison of sensory threshold testing parameters between 20 long
      standing refractory patients with CRPS who have TBP versus 10 healthy
      participants. METHODS: Twenty patients with CRPS who stated that they suffered
      from total body pain were chosen from the Drexel University College of Medicine
      CRPS database. They were compared to 10 healthy participants that were age and
      gender matched to the patients with CRPS. The sensory parameters tested were:
      skin temperature; static and mechanical allodynia; thermal allodynia; mechanical
      hyperalgesia; after sensations following all sensory tests. The sites chosen for
      testing in the patients with CRPS were the most painful area in each of 8 body
      regions that comprised the total body area. RESULTS: Five patients with CRPS had
      signs of CRPS over 100% of their body (20%). One patient had pain over 87% and
      another had pain over 90% of their body area. The average percentage of body
      involvement was 62% (range 37% - 100%). All patients with CRPS had at least one
      sensory parameter abnormality in all body regions. All patients with CRPS had
      lower pain thresholds for static allodynia in all body areas, while 50%
      demonstrated a lower threshold for dynamic allodynia in all body regions compared
      to the healthy participants. Cold allodynia had a higher median pain rating on
      the Likert pain scale in all body areas versus healthy participants except for
      the chest, abdomen, and back. Eighty-five percent of the patients with CRPS had a
      significantly lower pain threshold for mechanical hyperalgesia in all body areas
      compared to the healthy participants. After sensations occurred after all sensory
      parameters in the extremities in patients with CRPS. LIMITATIONS: The primary
      limitations of this study would be the variability of self-reported data (each
      subject's assessment of pain/ discomfort to a tested parameter) and the challenge
      to uniformly administer each parameter's assessment since simple tools and not
      precision instruments were used (with the exception of skin temperature).
      CONCLUSIONS: TBP and objective sensory loss occur in 20% of patients with
      refractory long-standing CRPS.

PMID- 24284844
TI  - Can we predict addiction to opioid analgesics? A possible tool to estimate the
      risk of opioid addiction in patients with pain.
AB  - BACKGROUND: The use of opioid analgesics in the treatment of chronic pain
      conditions has long been controversial. They have been reported to be relatively
      safe when prescribed with caution, but a brief and valid instrument to estimate a
      person's risk of addiction is still missing. OBJECTIVE: The aim of this study was
      to investigate a self-rating questionnaire allowing an estimation of a person's
      risk of addiction to opioid analgesics. STUDY DESIGN: Retrospective review.
      SETTING: Four Austrian hospitals. METHODS: Seven hundred forty-one patients were
      interviewed. Of these, 634 patients were affected with chronic pain while 107
      patients had a history of opioid addiction. Patients were interviewed about
      alcohol and nicotine consumption and family history of psychiatric disorders.
      Attitudes towards medication and the origin of pain were examined. We asked
      patients with an opioid addiction and patients suffering from chronic pain to
      complete a short questionnaire intended to help screen for addiction potential.
      RESULTS: Compared to the patients suffering from chronic pain, patients with an
      opioid addiction significantly more often had alcohol- and nicotine-related
      pathologies and psychiatric comorbidity. A family history of mental illness and
      developmental problems were significantly more frequent in this group. Compared
      to those not addicted, those with an opioid addiction had significantly higher
      expectations concerning the potential of medication to change one's mental state;
      they thought that psychological  factors might contribute to the pain they feel.
      LIMITATIONS: The main limitation of this study is the use of a self-rating
      instrument which reduces objectivity and introduces the possibility of
      misreporting. Also, the 2 groups differ in number and are not homogenous.
      CONCLUSION: We found differences in questionnaire responses between patients with
      an opioid addiction and patients suffering from chronic pain to be dependent upon
      the prevalence of current or former addiction, psychiatric history, attitudes
      towards medication, and ideas about the origin of pain. We believe these factors
      have predictive value in estimating a patient with pain's risk of addiction.

PMID- 24284845
TI  - A comparison of chronic pain prevalence in Japan, Thailand, and myanmar.
AB  - BACKGROUND: Pain has been regarded as important in the improvement of quality of
      life (QOL). In the advanced countries of Europe and the North America, a number
      of large-scale epidemiological surveys on pain, particularly chronic pain, have
      thus been performed in general populations. However, few epidemiological surveys
      of chronic pain have been reported from developing countries, and no surveys
      appear to have examined chronic pain in the least developed countries.
      OBJECTIVES: To compare the incidence of chronic pain in Asian countries, using
      Japan as an advanced country, Thailand as a developing country, and Myanmar as
      one of the least developed countries. STUDY DESIGN: Cross-sectional study in 4
      hospitals. SETTING: A university hospital and a general hospital in Japan, a
      university hospital in Thailand, and a general hospital in Myanmar. METHODS:
      Patients were 1,000 nursing staff working in Japan, 448 nursing staff working in
      Thailand, and 405 nursing staff working in Myanmar. The survey was performed by
      requesting all nursing staff to anonymously answer the questionnaire. Data were
      used to calculate chronic pain prevalence, pain site, presence or absence of
      consultation with doctors, methods of handling pain other than consultation with
      doctors, and whether pain was controlled for each country. The results were then
      compared between countries. RESULTS: The prevalence of chronic pain in Myanmar
      was 5.9%, which was significantly lower (P < 0.01) than in Japan (17.5%) or
      Thailand (19.9%). The most frequent pain sites were the lower back, head, and
      shoulders in Japan, and the shoulders, ankle, upper back, and head in Thailand,
      whereas in Myanmar, no clear certain tendencies were observed. The most frequent
      method for handling pain other than consultation with doctors was over-the
      counter drugs in Japan, massage in Thailand, and relaxation therapy (meditation)
      in Myanmar. LIMITATIONS: Limitations of this study were the cross-sectional
      design study, the small number of hospitals included, the limitation of patients
      to nursing staff, and the omission from the questionnaire of questions regarding
      body height and weight, working situation, family background, trauma history,
      sports activity history, smoking history, psychological/character tests, QOL, and
      pain levels of patients. CONCLUSION: The prevalence of chronic pain was
      significantly lower in Myanmar than in Japan or Thailand. With regard to the site
      and treatment of chronic pain, no clear tendencies were observed between
      countries, suggesting that frequency and the character of chronic pain differ
      from country to country around the world.

PMID- 24284847
TI  - Drug therapy for the treatment of chronic nonspecific low back pain: systematic
      review and meta-analysis.
AB  - BACKGROUND: Low back pain (LBP) is one of the most common health problems in
      adults. The impact of LBP on the individual can cause loss of health status in
      the form of symptoms and loss of function related to pain in the back; limitation
      of daily, leisure, and/or strenuous activities, and disability. LBP also poses an
      economic burden to society, mainly in terms of one of the most common reasons for
      seeking medical care (direct treatment costs), and accounts for the large number
      of work days lost (indirect costs). To reduce the impact of LBP on adults, drug
      therapy is the most frequently recommended intervention. Over the last decade, a
      substantial number of randomized clinical trials of drug therapy for LBP have
      been published. OBJECTIVE: To determine the effectiveness of drug therapy for the
      treatment of chronic nonspecific low back pain (CNLBP). STUDY DESIGN: Systematic
      review METHODS: A systematic review and meta-analysis of randomized controlled
      trials was conducted. Five databases (Medline, CINAHL, Science Direct, CAJ Full
      text Database, and Cochrane databases) were searched for articles published from
      2002 to 2012. The eligibility criteria were randomized trials and double-blind
      controlled trials of oral or injection drug therapy for CNLBP in subjects who
      were aged at least 18 years old, published in English or Chinese. Two independent
      reviewers extracted the data.  RESULTS: A total of 25 drug therapy trials were
      included. cyclo-oxygenase-2 (COX-2) nonsteroidal anti-inflammatory drugs
      (NSAIDs), tramadol, and opioids were commonly used. Only 5 trials studied the
      efficacy of adjuvant analgesics of antiepileptics (n = 1) and antidepressants (n
      = 4) for CNLBP. The standardized mean difference (SMD) for COX-2 NSAIDs in pain
      relief was -12.03 (95% confidence interval [CI]: -15.00 to -9.06). The SMD for
      tramadol in pain relief was -1.72 (95% CI: -3.45 to 0.01). As the 95% CI crossed
      0, this effect size was not considered statistically significant. The SMD for the
      overall effects of opioids in pain relief was -5.18 (95% CI: -8.30 to -2.05). The
      SMD for the partial opioid agonist drug in pain relief was -7.46 (95% CI: -11.87
      to -3.04). LIMITATIONS: The follow-up periods of these included trials in the
      meta-analysis ranged from 4 to 24 weeks. The difference of follow-up periods
      influenced how study outcomes were recorded. These included trials also had
      significant differences in patient selections. Some trials may actually include
      CNLBP patients with neuropathic pain, as not having focal neurological findings
      or signs does not mean that the pain is not neuropathic. Consequently, different
      pain conditions may influence patients who responded to the same drug and then
      influence pooled estimates of treatment effect size. CONCLUSION: This review
      endorses the use of COX-2 NSAIDs as the first-line drugs for CNLBP. Tramadol
      shows no statistically significant effect on pain relief, but has small effect
      sizes in improving functioning. Among included opioid therapy studies, the
      overall effects of opioids and the partial opioids agonist drug had statistically
      significant treatment effects in pain relief for CNLBP patients.

PMID- 24284848
TI  - In response to paresthesia coverage for comparing the inhibition of somatosensory
      evoked potentials by spinal cord stimulation and transcutaneous electrical nerve
      stimulation.

PMID- 24284849
TI  - Accountable interventional pain management: a collaboration among practitioners,
      patients, payers, and government.
AB  - The prevalence, costs, and disability associated with chronic pain continue to
      escalate. So too, the numerous modalities of treatments applied in managing these
      patients continue to increase as well. In the period from 2000 to 2011
      interventional techniques increased 228%. In addition, analysis of utilization
      trends and expenditures for spinal interventional techniques alone from 2000 to
      2008 illustrated an increase in Medicare fee-for-service expenditures of 240% in
      terms of dollars spent in the United States. The Office of Inspector General
      (OIG) of the Department of Health and Human Services showed an increase in facet
      joint and transforaminal epidural injections, with a significant proportion of
      these services did not meet the medical necessity criteria.The increasing
      utilization of interventional techniques is also associated with significant
      variations among specialty groups and regional variations among states. Overall
      procedures have increased by 173%, with rate of 130% per 100,000 Medicare
      beneficiaries for epidural injections; 383%, with a rate of 308% for facet joint
      interventions; and overall 410%, or a rate of 331% for sacroiliac joint
      interventions. Certain high volume interventions such as lumbar transforaminal
      epidural injections and lumbar facet joint neurolysis have actually increased a
      staggering 806% and 662%.Coverage policies across ambulatory settings and by
      multiple payers are highly variable. Apart from variability in the development of
      coverage policies, payments also substantially vary by site of service. In
      general, amongst the various ambulatory settings the highest payments are made to
      hospital outpatient departments (HOPDs)  the lowest to in-office procedures, and
      payment to ambulatory surgery centers (ASCs) falling somewhere in the middle.This
      manuscript describes the many differences that exist between the various
      settings, and includes suggestions for accountable interventional pain management
      with coverage for techniques with evidence, addressing excessive use of specific
      techniques, and equalizing payments across multiple ambulatory settings. 

PMID- 24284850
TI  - Prevalence of pain among nonmedical prescription opioid users in substance use
      treatment populations: systematic review and meta-analyses.
AB  - BACKGROUND: Prescription opioid analgesics (POA) are widely used in the
      pharmacotherapeutic treatment of acute and chronic pain in North America, where
      nonmedical prescription opioid use (NMPOU) has become a substantial public health
      concern in recent years. Existing epidemiological data suggest an association
      between NMPOU and pain problem symptoms in different populations, including
      samples in substance use treatment, although the extent of these correlations has
      not been systematically assessed. OBJECTIVE: To systematically review and meta
      analyze the prevalence of pain symptoms or problems among populations reporting
      NMPOU in substance use treatment. STUDY DESIGN: Systematic review and meta
      analyses. METHODS: A systematic review and meta-analyses were conducted for pain
      symptoms in substance use treatment samples reporting NMPOU within the last 30
      days or at admission to treatment. Overall, 8 unique epidemiological studies were
      identified and included in the meta-analyses; in 7 of these samples POAs were the
      primary drug and/or POA dependence was reported. RESULTS: The pooled prevalence
      of pain in all NMPOU samples in substance use treatment was 58% (95% confidence
      interval [CI]: 53%-64%). The pooled prevalence of pain in the studies with POAs
      as the primary drug and/or POA dependence was 60% (95% CI: 52%-67%), and the
      prevalence of pain with "any" POA abuse (n = 2 studies) was 50% (95% CI: 40%
      60%). LIMITATIONS:   A small number of studies were available and included in the
      review; these were restricted to cross-sectional datasets only. Statistical
      heterogeneity was found in the meta-analytical results. CONCLUSIONS: Pain
      symptoms are disproportionately elevated in substance use treatment samples
      reporting NMPOU. Effective measures to prevent and treat NMPOU are urgently
      needed, although a substantive extent of NMPOU observed in this specific context
      may relate directly or indirectly to the presence of pain, e.g., either as an
      expression of ineffective pain care or as a consequence of previous POA-based
      interventions. At the same time, effective ways to treat and address ongoing pain
      issues in NMPOU samples need to be implemented, which may require ongoing opioid
      based pharmacotherapeutic care aimed at both pain and dependence.

PMID- 24284851
TI  - Comparative efficacy and safety of six antidepressants and anticonvulsants in
      painful diabetic neuropathy: a network meta-analysis.
AB  - BACKGROUND: Anticonvulsants and antidepressants are mostly used in management of
      painful diabetic neuropathy (PDN). However there are few direct comparisons
      between drugs of these classes, making evidence-based decision-making in the
      treatment of painful diabetic neuropathy difficult. OBJECTIVES: This study aimed
      to perform a network meta-analysis and benefit-risk analysis to evaluate the
      comparative efficacy and safety of these drugs in PDN treatment. STUDY DESIGN:
      Comparative effectiveness study. SETTING: Medical Education and Research facility
      in India. METHODS: A comprehensive data search was done in PubMed, Cochrane, and
      Embase up to August 2012. We then systematically reviewed the studies which
      compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine,
      gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations.
      We performed a random-effects network meta-analysis to rank treatments in terms
      of efficacy and safety. We chose the number of patients experiencing = 50%
      reduction in pain and number of patient withdrawals due to adverse events (AE) as
      primary outcomes for efficacy and safety, respectively. We also performed benefit
      risk analysis, taking efficacy outcome as benefit and safety outcome as risk.
      Analysis was intention-to-treat. RESULTS: We included 21 published trials in the
      analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be
      significantly efficacious compared to placebo with odds ratios (OR) of 2.12,
      3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence
      interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused
      more withdrawals than gabapentin. The ranking order of efficacy was gabapentin,
      venlafaxine, pregabalin, duloxetine/gabapentin, duloxetine, amitriptyline, and
      placebo and the ranking order of safety was placebo, gabapentin, pregabalin,
      venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline.
      Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin,
      duloxetine/gabapentin combination, duloxetine, placebo, and amitriptyline.
      LIMITATIONS: We could not include valproate in our analysis owing to the lack of
      studies reporting the dichotomous efficacy and safety outcomes. CONCLUSION:
      Gabapentin was found to be most efficacious and amitriptyline to be least safe
      among the treatments included in the study. Gabapentin showed most favorable
      balance between efficacy and safety.

PMID- 24284852
TI  - Gender difference of symptom severity in lumbar spinal stenosis: role of pain
      sensitivity.
AB  - BACKGROUND: Given that there are gender differences in pain perception, it is
      likely that there are differences in pain responses between men and women with
      lumbar spinal stenosis (LSS). Furthermore, these differences may lead to
      different degrees of impairment in both daily activities and quality of life
      between men and women. OBJECTIVE: To elucidate the difference of LSS symptom
      severity between genders in relation to pain sensitivity. STUDY DESIGN:
      Retrospective analysis of prospectively collected data. METHODS: A total of 160
      patients who had symptomatic degenerative lumbar spinal stenosis completed a
      series of questionnaires on their first visit in the outpatient clinic, including
      a pain sensitivity questionnaire (PSQ) (total PSQ and PSQ-minor), Oswestry
      Disability Index (ODI), visual analog scale (VAS) for back pain, and Short Form
      36 (SF-36). Using magnetic resonance images, the degree of canal stenosis and
      disc degeneration were graded based on the method by Schizas and the Pfirrmann
      classification, respectively. Symptom severity, pain sensitivity, and radiologic
      findings were compared between men and women. In each gender group analysis, the
      correlation between pain sensitivity and symptom severity was analyzed. RESULTS:
      After adjustment for age and the grade of disc degeneration, the pain sensitivity
      represented by total PSQ and PSQ-minor was significantly higher in women than in
      men. Moreover, there was a higher VAS for back pain/leg pain and ODI in women
      compared to men after adjustment for body mass index (BMI), age, and the grades
      of canal stenosis and disc degeneration. After additional adjustment for pain
      sensitivity including total PSQ and PSQ-minor, there was no difference in VAS for
      back pain/leg pain between genders. On the SF-36 women demonstrated a lower
      quality of life than men in terms of Physical Function, Role Physical, Bodily
      Pain, General Health, and Physical Component Summary. Each gender group analysis
      showed that pain sensitivity was associated with symptom severity and disability
      caused by LSS in both women and men. LIMITATIONS: The present study did not
      evaluate psychological factors including catastrophizing and/or undiagnosed
      personal traits which possibly can influence the severity of symptoms from LSS.
      CONCLUSIONS: Women showed increased low back pain and leg pain due to
      degenerative LSS compared to men. The current study demonstrates that this
      difference in symptom severity may be partly mediated by pain sensitivity.

PMID- 24284853
TI  - Needle echogenicity in ultrasound-guided lumbar spine injections: a cadaveric
      study.
AB  - BACKGROUND: Echogenicity of regional anesthesia needles has been tested on
      different preclinical models; however, previous studies were done in an ideal
      experimental setting utilizing high-frequency insonation and superficially
      located targets. Because steep-angle deep injections are typically required for
      spinal and other chronic pain procedures, and low-frequency transducers are used,
      further feasibility study is warranted. OBJECTIVES: To determine effectiveness of
      steep-angle deep injections, typically required for spinal and other chronic pain
      procedures. STUDY DESIGN: Experimental laboratory study. SETTING: Willed Body
      Program, University of Washington. METHODS: In-plane lumbar spine procedures with
      50 degrees  and 70 degrees  angles were performed on a human cadaver. The images
      and video clips of a non-echogenic (Quincke-type) and echogenic (SonoPlex,
      StimuQuick, and EchoStim) needle placements were presented to 3 blinded assessors
      who rated the needle visibility on a 4-point scale. The data was statistically
      analyzed to determine the differences in visibility between the needles with and
      without the digital image enhancement, and to compare the video clips to captured
      images. RESULTS: ANOVA analysis demonstrated that overall SonoPlex was
      significantly better (P = 0.02) than other needles. SonoPlex maintained its
      superiority in the subset of facet joint injections (P = 0.02), followed by
      Quincke-type, then the StimuQuik, and EchoStim needles. In deep procedures,
      EchoStim was comparable with SonoPlex (P = 0.03), and they both were better than
      the other 2 needles. The enhanced images received higher rates, with a 0.6 point
      mean improved rating (P = 0). LIMITATIONS: This study is limited by choice of
      needles, number of experiments performed, and potential postmortem changes of
      echogenicity. CONCLUSIONS: The SonoPlex needle appeared to have better
      echogenicity in this study. While non-echogenic Quincke-type needle visibility
      was adequate in superficial placements, it was limited in deep injections. An
      imaging enhancement is effective in improving needle visibility and should be
      used whenever possible.

PMID- 24284854
TI  - Fluoroscopy procedure and equipment changes to reduce staff radiation exposure in
      the interventional spine suite.
AB  - BACKGROUND: Fluoroscopic guided percutaneous interventional spine procedures are
      increasingly performed in recent years as they have been shown to be target
      specific and enhance patient safety. However, ionizing radiation has been
      associated with stochastic effects such as cancer and genetic defects as well as
      deterministic effects such as cataracts, erythema, epilation, and even death.
      These are dose related, and hence, measures should be taken to minimize radiation
      exposure to patients and health care personnel to reduce these adverse effects.
      OBJECTIVE: A risk reduction project was completed with the goal of reducing
      effective doses to the staff and patients in a university-based spinal
      interventional practice. Effective dose reduction to the staff and patients was
      hypothesized to occur with technique and equipment changes in the procedure
      suite. The goal of this study was to quantify effective dose rates to staff
      before and after interventions. STUDY DESIGN: Retrospective study comparing
      descriptive data of effective dose to the health care staff before and after
      implementation of a combination of technique and equipment changes. METHODS:
      Technique changes from pre to post intervention period included continuous needle
      advancement under continuous fluoroscopic controlled by the interventional
      physician to intermittent needle advancement under pulsed fluoroscopic controlled
      by the radiology technician. Equipment changes included circumferential lead
      drape skirt around the procedure table and use of mobile transparent lead
      barriers on both sides of the procedure table.Effective dose exposure measured in
      Millirem (mrem) from the radiation dosimetry badges for pre-intervention
      (February 2009 through June 2009) and post-intervention (November 2009 through
      March 2010) periods were examined through monthly radiation dosimetry reports for
      the fluoroscopy suite staff. RESULTS: A total of 685 interventional procedures
      were performed in the pre-intervention period and 385 in the post-intervention
      period. The median cumulative mrem (interquartile range) for all staff combined
      in the pre-intervention period was 71 (28,75) and post-intervention period was 1
      (0,3). The median mrem per procedure was significantly higher in the pre
      intervention group 0.46 (0.36, 0.54) compared to post-intervention 0.01 (0.0.03);
      P < 0.01. The percentage reduction in overall effective dose per procedure to all
      staff was 97.3%. LIMITATIONS: Observational study, multiple radiation reduction
      interventions confound the individual effects of each intervention's effective
      dose CONCLUSIONS: Spinal injection technique and equipment changes in the
      procedure suite significantly reduced the rate of effective dose to the clinical
      staff.

PMID- 24284855
TI  - Long-term consequences of acute pain for patients under methadone or
      buprenorphine maintenance treatment.
AB  - BACKGROUND: Acute and chronic pains are reported to be highly prevalent in
      patients under opioid maintenance treatment (OMT). Lack of knowledge concerning
      the complex relationship between pain, opioid use, and their impact on OMT
      efficacy can account for the barriers encountered for pain management.
      OBJECTIVES: To assess the impact of acute pain exposure on long-term OMT
      retention in a cohort of patients under buprenorphine or methadone followed up
      during 12 months. STUDY DESIGN: Prospective, multi-center observational cohort
      clinical study. SETTING: Emergency departments, surgery departments, and
      specialized addiction care centers in an outpatient setting in south-western
      France (Midi-Pyrenees area), from April 2008 to January 2010. METHODS: Patients
      aged 18 or more under OMT for at least 3 months, and followed up by a physician
      were recruited. Acute pain was assessed using the Visual Analog Scale (VAS) or
      the Verbal Rating Scale (VRS). Exposed patients were those with a pain score
      greater than 0 at the time of admission on any of the rating scales. The OMT rate
      after 12 months was compared among exposed and unexposed patients. OMT retention
      was also investigated after 3 and 6 months follow-up. RESULTS: A total of 151
      patients, 81 exposed and 70 unexposed, were recruited; among them, respectively,
      26 (32%) and 34 (49%) completed 12-months follow-up. Acute pain exposure appeared
      to be significantly and negatively associated with retention in treatment (crude
      OR: 0.44; 95% CI [0.22 - 0.87]; adjusted OR: 0.46; 95% CI [0.23 - 0.93]).
      Compared to methadone users, patients under buprenorphine were less likely to
      have their OMT maintained after 12 months (OR 0.37; 95% CI [0.18 - 0.75];
      adjusted OR 0.38; 95% CI [0.18 - 0.80]). LIMITATIONS: Follow-up rate was 40%
      (60/151). CONCLUSION: This study demonstrates the strong negative impact of acute
      pain on OMT in a population mainly composed of patients under buprenorphine, as
      well as differential response depending on the OMT medication. The findings
      highlight the need to consider the characteristics of pain in the population
      under OMT and to develop evidence-based guidelines for pain management. TRIAL
      REGISTRATION: The study was registered at www.clinical.trials.gov with the study
      identifier: NCT00738036. Ethics Committee approval was received on February 11,
      2008. Participants' written consent was not required.

PMID- 24284857
TI  - Importance of axial migration of spinal cord stimulation trial leads with
      position.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is an established treatment option for
      chronic pain. Prior to permanent implantation, temporary trials are performed to
      evaluate the SCS treatment. During the trial period, it is common for the
      patients to experience changes in paresthesias. However, it is unclear what the
      role of lead migration is, if any, in the changes in paresthesia. OBJECTIVE: To
      evaluate the role of lead migration on the effect of postural stimulation changes
      during SCS trials. STUDY DESIGN: Case series. SETTING: University pain management
      center. METHODS: X-rays of the patients with successful trials, in sitting and
      standing position, were obtained at the end of a 7 day SCS trial. Data were
      collected based on the need for adjustment of the stimulation settings due to
      changes in paresthesias with postural change of sitting versus standing. RESULTS:
      The average lead migration was 3.05 mm inferiorly from a standing to sitting
      position for all subjects. The average migration was 2.85 mm in subjects
      requiring adjustment of the SCS setting due to change in paresthesia compared to
      3.24 mm for those who did not require adjustment regardless of position. The
      results were insignificant based on P = 0.17. LIMITATIONS: Small sample size,
      case series. CONCLUSIONS: This case series demonstrates continued support for the
      role of the width of the cerebral spinal fluid space as the significant factor on
      paresthesia changes in SCS with respect to postural changes, even during the
      trial period.

PMID- 24284856
TI  - Randomized clinical trial evaluating transdermal Ibuprofen for moderate to severe
      knee osteoarthritis.
AB  - BACKGROUND: Osteoarthritis is a common condition, typically treated with orally
      administered analgesics and non-steroidal anti-inflammatory drugs (NSAIDs).
      Chronic administration of NSAIDs, serotonin-norepinephrine reuptake inhibitors
      (SNRIs, i.e., duloxetine), and opioid medications (i.e., tramadol) is regularly
      associated with multiple, serious side effects, in part due to the route of
      administration. Transdermal delivery of NSAIDs, such as ibuprofen, represents a
      potentially alternative treatment for this inflammatory pain condition with a
      better therapeutic profile. OBJECTIVE: Investigate the safety and efficacy of a
      novel transdermal ibuprofen formulation (VALE(r)-ibuprofen) containing 10%
      ibuprofen, compared to a placebo in a randomized, double-blinded clinical trial,
      for clinical improvement in patients with moderate to severe painful
      osteoarthritis of the knee. STUDY DESIGN: A randomized, placebo-controlled,
      double blind, multi-center Phase 2 clinical trial. SETTING: An academic medical
      center, and private rheumatology and interventional pain management practices.
      METHODS: The Phase 2 clinical study included patients with primary osteoarthritis
      in a single knee joint with a progression level of moderate to severe based in
      part on a grade II or III designation according to the Kellgren and Lawrence
      classification system. Patients received the corresponding, randomly assigned
      study formulation (VALE-ibuprofen or placebo) for application to the target knee
      at a dose of 2.0 grams of drug product (200 mg ibuprofen) twice daily for 14
      days. The evaluation of the efficacy of the treatments utilized the widely
      accepted methods of the Western Ontario and McMaster Universities (WOMAC)
      Osteoarthritis Index and the Visual Analog Scale (VAS) scores for the patients.
      RESULTS: The results indicate that the transdermal VALE-ibuprofen formulation was
      very well tolerated from a safety perspective during the 2-week trial and also
      produced significant, positive clinical improvements superior to the placebo in
      all clinical endpoints tested. In particular, the WOMACTotal and WOMACPhysical
      Functioning, for the VALE-ibuprofen, were superior compared to the placebo (P =
      0.0283 and P = 0.0201, respectively). Other clinical endpoints including the
      WOMACPain, WOMACStiffness, and VASResting scores were superior to those obtained
      from the placebo group, trending towards statistical significance compared to
      placebo (P = 0.0811, 0.1103, and 0.0785, respectively). Based on the Patient and
      Physician Global Impression of Change survey, patient satisfaction slightly
      improved across both groups; however, no statistical significance was detectable
      as compared to the baseline. LIMITATIONS: The sample size of 64 subjects in the
      final data analysis and the lack of including an orally administered drug group
      are limitations of this study. CONCLUSIONS: The use of transdermal VALE-ibuprofen
      has beneficial clinical effects on the pain levels experienced in some patients
      with moderate to severe osteoarthritis of the knee as measured by the WOMAC
      Osteoarthritis Indices for stiffness, pain, physical function, and total. Visual
      Analog Scales (VAS) tests, VASMotion and VASWeight-bearing, again while appeared
      superior to placebo, were not statistically different from placebo. CLINICAL
      TRIAL REGISTRATION: NCT01496326.

PMID- 24284858
TI  - A novel revision to the classical transnasal topical sphenopalatine ganglion
      block for the treatment of headache and facial pain.
AB  - BACKGROUND: The sphenopalatine ganglion (SPG) is located with some degree of
      variability near the tail or posterior aspect of the middle nasal turbinate. The
      SPG has been implicated as a strategic target in the treatment of various
      headache and facial pain conditions, some of which are featured in this
      manuscript. Interventions for blocking the SPG range from minimally to highly
      invasive procedures often associated with great cost and unfavorable risk
      profiles. OBJECTIVE: The purpose of this pilot study was to present a novel, FDA
      cleared medication delivery device, the Tx360(r) nasal applicator, incorporating
      a transnasal needleless topical approach for SPG blocks. This study features the
      technical aspects of this new device and presents some limited clinical
      experience observed in a small series of head and face pain cases. STUDY DESIGN:
      Case series. SETTINGS: Pain management center, part of teaching-community
      hospital, major metropolitan city, United States. METHODS: After Institutional
      Review Board (IRB) approval, the technical aspects of this technique were
      examined on 3 patients presenting with various head and face pain conditions
      including trigeminal neuralgia (TN), chronic migraine headache (CM), and post
      herpetic neuralgia (PHN). The subsequent response to treatment and quality of
      life was quantified using the following tools: the 11-point Numeric Rating Scale
      (NRS), Modified Brief Pain Inventory - short form (MBPI-sf), Patient Global
      Impression of Change (PGIC), and patient satisfaction surveys. The Tx360(r) nasal
      applicator was used to deliver 0.5 mL of ropivacaine 0.5% and 2 mg of
      dexamethasone for SPG block. Post-procedural assessments were repeated at 15 and
      30 minutes, and on days one, 7, 14, and 21 with a final assessment at 28 days
      post-treatment. All patients were followed for one year. Individual patients
      received up to 10 SPG blocks, as clinically indicated, after the initial 28 days.
      RESULTS: Three women, ages 43, 18, and 15, presented with a variety of headache
      and face pain disorders including TN, CM, and PHN. All patients reported
      significant pain relief within the first 15 minutes post-treatment. A high degree
      of pain relief was sustained throughout the 28 day follow-up period for 2 of the
      3 study participants. All 3 patients reported a high degree of satisfaction with
      this procedure. One patient developed minimal bleeding from the nose immediately
      post-treatment which resolved spontaneously in less than 5 minutes. Longer term
      follow-up (up to one year) demonstrated that additional SPG blocks over time
      provided a higher degree and longer lasting pain relief. LIMITATIONS: Controlled
      double blind studies with a higher number of patients are needed to prove
      efficacy of this minimally invasive technique for SPG block. CONCLUSION: SPG
      block with the Tx360(r) is a rapid, safe, easy, and reliable technique to
      accurately deliver topical transnasal analgesics to the area of mucosa associated
      with the SPG. This intervention can be delivered in as little as 10 seconds with
      the novice provider developing proficiency very quickly. Further investigation is
      certainly warranted related to technique efficacy, especially studies comparing
      efficacy of Tx360 and standard cotton swab techniques.

PMID- 24284859
TI  - A case vignette study to assess the knowledge of pain physicians of neuropathic
      cancer pain: room for improvement.
AB  - BACKGROUND: In more and more countries, a specific pain education curriculum is
      provided to instruct pain physicians. However, there is little literature on pain
      education and in particularly how to evaluate their knowledge. One of the modules
      interesting to assess is the use of clinical practice guidelines (CPGs) by pain
      physicians. OBJECTIVES: The aim was to investigate if a case vignette is useful
      to evaluate pain physicians' knowledge about recommendations contained in CPGs.
      SETTING: An email survey was conducted with the support of the Societe Francaise
      d'Etude et de Traitement de la Douleur to all pain specialists (primary and
      secondary care) in France. METHODS: The survey consisted of a case vignette about
      a patient with pain suffering from an intractable pancreatic cancer with multiple
      choice questions about diagnosis and treatment of pain. Percentages of
      participants who treated the patient as suggested in the CPGs were calculated.
      RESULTS: A total of 214 of those invited to participate (921) answered the
      questionnaire (24%). More than 85% of the respondents declared to know and use
      CPGs. Half of the participants diagnosed and treated neuropathic pain components
      in the case vignette according to the recommendations in the CPGs. LIMITATIONS:
      This exercise needed to be explained: pain physicians should be trained to this
      kind of questionnaire. It explains the low response rate and the progressive
      diminution of responders during the questionnaire. CONCLUSIONS: Case vignette is
      an interesting instrument for pain education because it is cheap, easy to use,
      and can be repeated. However, training before using this instrument is needed for
      pain physicians, in particular during their pain education.

PMID- 24284860
TI  - Permanent implantation of peripheral nerve stimulator for combat injury-related
      ilioinguinal neuralgia.
AB  - A peripheral nerve stimulator (PNS) can be an alternative for long-term pain
      relief refractory to conventional therapeutic modalities. We present a case of
      chronic incapacitating ilioinguinal neuralgia, which was successfully managed
      with permanent implantation of a peripheral nerve stimulator. A 26-year-old
      active duty African American man was referred to the University Pain Clinic with
      left ilioinguinal neuralgia due to shrapnel injury during his military service 6
      years prior to his visit. Most of the shrapnel were surgically removed, but the
      patient subsequently developed left lower abdominal pain. Multiple surgeries,
      including inguinal herniorrhaphy, varicocelectomy, and orchiectomy, failed to
      provide satisfactory relief of his neuralgia. Other therapies tried resulting in
      limited outcomes were multiple ilioinguinal nerve blocks and cryoanalgesia. A
      trial of PNS was successful and the implantation of permanent leads was carried
      out. At his 3-month visit, the patient reported to have minimal pain, was tapered
      off oral analgesics, was able to return to work, and had resumed his normal daily
      activities. Recent technological advances in programming software and surgical
      techniques have led to renewed interest in PNS for the treatment of chronic
      refractory peripheral nerve injury. Despite our limited understanding of its
      exact mechanism of action, it can be considered as a therapeutic potential for a
      few carefully selected, intractable cases. Its minimally invasive and reversible
      features make PNS a favorable option for these patients. The stringent and
      rigorous screening procedures for suitable candidacy, documentation of previously
      failed treatments, psychiatric evaluation, and 3-5 days of preplacement trial,
      improve the success rate. 

PMID- 24284861
TI  - Pudendal entrapment neuropathy: a rare complication of pelvic radiation therapy.
AB  - Pudendal nerve entrapment (PNE) is an uncommon cause of chronic pain. Pudendal
      nerve entrapment typically occurs when the pudendal nerve is fused to nearby
      anatomical structures or trapped between the sacrotuberous and sacrospinalis
      ligaments. Pudendal nerve entrapment can be caused by excessive bicycling,
      pregnancy, anatomic abnormalities, scarring due to surgery, or as a sequela of
      radiation therapy. Radiation-induced peripheral neuropathy is usually chronic,
      progressive, and often irreversible. Radiation-induced pudendal neuropathy is
      much less common than the more familiar brachial plexopathy secondary to
      radiation treatment for breast cancer. The prevalence of PNE, however, is
      increasing due to improved long-term cancer survival. Diagnosis of pudendal
      neuralgia is essentially clinical; no specific clinical signs or complementary
      tests are reliably confirmatory. A detailed pain history with correlative
      clinical examination is paramount for accurate diagnosis. Performance of a
      pudendal nerve block can serve as both a diagnostic and therapeutic tool.
      Utilization of various imaging studies, as well as the performance of an
      electrophysiological study with pudendal nerve motor latency testing, may yield
      valuable evidence in support of a pudendal neuralgia diagnosis. We present the
      case of a 59-year-old man with stage IV prostate cancer, referred to the pain
      clinic for chronic perineal and right sided pelvic pain. His pain began
      insidiously, approximately 2 months after undergoing radiation treatment and
      chemotherapy 3 years prior. He was ultimately diagnosed as having a right sided
      pudendal entrapment neuropathy. His pain was refractory to all conventional
      treatment modalities; therefore we decided to pursue neuromodulation via a dorsal
      column spinal cord stimulator implant. Below, we describe the decision making
      process for the diagnosis and treatment of his pudendal neuropathy. 

PMID- 24284862
TI  - Ultrasound-guided anterior abdominal cutaneous nerve block for the management of
      bilateral abdominal cutaneous nerve entrapment syndrome (ACNES).

PMID- 24284863
TI  - Paresthesia coverage for comparing the inhibition of somatosensory evoked
      potentials by spinal cord stimulation and transcutaneous electrical nerve
      stimulation.

PMID- 24284866
TI  - Functional relationships between leaf hydraulics and leaf economic traits in
      response to nutrient addition in subtropical tree species.
AB  - Leaves can be both a hydraulic bottleneck and a safety valve against hydraulic
      catastrophic dysfunctions, and thus changes in traits related to water movement
      in leaves and associated costs may be critical for the success of plant growth. A
      4-year fertilization experiment with nitrogen (N) and phosphorus (P) addition was
      done in a semideciduous Atlantic forest in northeastern Argentina. Saplings of
      five dominant canopy species were grown in similar gaps inside the forests (five
      control and five N + P addition plots). Leaf lifespan (LL), leaf mass per unit
      area (LMA), leaf and stem vulnerability to cavitation, leaf hydraulic conductance
      (K(leaf_area) and K(leaf_mass)) and leaf turgor loss point (TLP) were measured in
      the five species and in both treatments. Leaf lifespan tended to decrease with
      the addition of fertilizers, and LMA was significantly higher in plants with
      nutrient addition compared with individuals in control plots. The vulnerability
      to cavitation of leaves (P50(leaf)) either increased or decreased with the
      nutrient treatment depending on the species, but the average P50(leaf) did not
      change with nutrient addition. The P50(leaf) decreased linearly with increasing
      LMA and LL across species and treatments. These trade-offs have an important
      functional significance because more expensive (higher LMA) and less vulnerable
      leaves (lower P50(leaf)) are retained for a longer period of time. Osmotic
      potentials at TLP and at full turgor became more negative with decreasing
      P50(leaf) regardless of nutrient treatment. The K(leaf) on a mass basis was
      negatively correlated with LMA and LL, indicating that there is a carbon cost
      associated with increased water transport that is compensated by a longer LL. The
      vulnerability to cavitation of stems and leaves were similar, particularly in
      fertilized plants. Leaves in the species studied may not function as safety
      valves at low water potentials to protect the hydraulic pathway from water stress
      induced cavitation. The lack of rainfall seasonality in the subtropical forest
      studied probably does not act as a selective pressure to enhance hydraulic
      segmentation between leaves and stems.

PMID- 24284865
TI  - Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus
      MVA immunisation.
AB  - Induction of antigen-specific CD8(+) T cells offers the prospect of immunization
      against many infectious diseases, but no subunit vaccine has induced CD8(+) T
      cells that correlate with efficacy in humans. Here we demonstrate that a
      replication-deficient chimpanzee adenovirus vector followed by a modified
      vaccinia virus Ankara booster induces exceptionally high frequency T-cell
      responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the
      liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile
      protective efficacy against heterologous strain sporozoites in three vaccinees
      (3/14, 21%), and delays time to patency through substantial reduction of liver
      stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls.
      The frequency of monofunctional interferon-gamma-producing CD8(+) T cells, but
      not antibodies, correlates with sterile protection and delay in time to patency
      (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against
      human malaria, suggesting that a major limitation of previous vaccination
      approaches has been the insufficient magnitude of induced T cells.

PMID- 24284867
TI  - Impact of anticoagulation on the effectiveness of loop diuretics in heart failure
      with cardiorenal syndrome and venous thromboembolism.
AB  - The limitations of diuretics in the treatment of acute decompensated heart
      failure (ADCHF) are progressive worsening of renal function and resistance to up
      titrated doses. The occurrence of resistance to loop diuretics in patients with
      ADCHF is associated with worsening prognosis and increased mortality. In this
      study, we report two patients with ADCHF and resistance to loop diuretics
      suspected for venous thromboembolism, suggesting that heparin administered to
      ADCHF patients treated for venous thromboembolism with cardiorenal syndrome
      decreases right-ventricular overload and improves renal function. To our
      knowledge, these are the first reported cases describing restored responsiveness
      to loop diuretics in ADCHF patients after additional heparin administration. 

PMID- 24284869
TI  - Rationalizing Overhauser DNP of nitroxide radicals in water through MD
      simulations.
AB  - The recently introduced methodology (Sezer, Phys. Chem. Chem. Phys., 2013, 15,
      526) for calculating dynamic nuclear polarization (DNP) coupling factors through
      synergistic use of molecular dynamics (MD) simulations and the analytical model
      of diffusing hard spheres with spins at their centers (HSCS) is applied to
      several nitroxides in water. Computations with one TEMPONE and one TEMPOL in
      water agree with experiments at 0.35 T and 3.4 T, respectively. At 9.2 T the
      predicted coupling factors are larger by about 50% than the experimental numbers
      obtained with 1 M TEMPOL solution. MD simulations at this elevated concentration
      reveal nanoscopic TEMPOL clusters and qualitatively explain the lower
      experimental values. Comparing the dynamics from the MD simulations with those of
      the HSCS model, the assumption of centered spins is shown to be too limiting even
      for small molecules like TEMPOL and water. Using the available extension of the
      HSCS model to off-centered spins, the current procedure for analyzing hydration
      water dynamics from Overhauser DNP measurements on spin-labeled proteins is
      revisited. 

PMID- 24284868
TI  - Cutaneous location of atypical teratoid/rhabdoid tumour.
AB  - Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the
      posterior fossae nervous system that occurs in children especially in the first
      few years of life. Cutaneous location is not previously reported. A newborn boy
      was referred for both aqueductal stenosis detected antenatally and skin tags
      mimicking hamartoma. The cerebral tumour increased in size during a few months
      leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1)
      immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the
      atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1
      immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour.
      Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour.
      The loss of Integrase INI-1 on immunohistochemical staining is characteristic. 

PMID- 24284870
TI  - Interfacial magnetism and exchange coupling in BiFeO3-CuO nanocomposite.
AB  - Ferromagnetic BiFeO3 nanocrystals of average size 9 nm were used to form a
      composite with antiferromagnetic CuO nanosheets, with the composition
      (x)BiFeO3/(100-x)CuO, x = 0, 20, 40, 50, 60, 80 and 100. The dispersion of BiFeO3
      nanocrystals into the CuO matrix was confirmed by x-ray diffraction and
      transmission electron microscopy. The ferromagnetic ordering as observed in pure
      BiFeO3 occurs mainly due to the reduction in the particle size as compared to the
      wavelength (62 nm) of the spiral modulated spin structure of the bulk BiFeO3.
      Surface spin disorder of BiFeO3 nanocrystals gives rise to an exponential
      behavior of magnetization with temperature. Strong magnetic exchange coupling
      between the BiFeO3 nanocrystal and the CuO matrix induces an interfacial
      superparamagnetic phase with a blocking temperature of about 80 K. Zero field and
      field cooled magnetizations are analyzed by a ferromagnetic core and disordered
      spin shell model. The temperature dependence of the calculated saturation
      magnetization exhibits three magnetic contributions in three temperature regimes.
      The BiFeO3/CuO nanocomposites reveal an exchange bias effect below 170 K. The
      maximum exchange bias field HEB is 1841 Oe for x = 50 at 5 K under field cooling
      of 50 kOe. The exchange bias coupling results in an increase of coercivity of
      1934 Oe at 5 K. Blocked spins within an interfacial region give rise to a
      remarkable exchange bias effect in the nanocomposite due to strong magnetic
      exchange coupling between the BiFeO3 nanocrystals and the CuO nanosheets.

PMID- 24284871
TI  - The prevalence and risk factors of dysmenorrhea.
AB  - Dysmenorrhea is a common menstrual complaint with a major impact on women's
      quality of life, work productivity, and health-care utilization. A comprehensive
      review was performed on longitudinal or case-control or cross-sectional studies
      with large community-based samples to accurately determine the prevalence and/or
      incidence and risk factors of dysmenorrhea. Fifteen primary studies, published
      between 2002 and 2011, met the inclusion criteria. The prevalence of dysmenorrhea
      varies between 16% and 91% in women of reproductive age, with severe pain in 2%
      29% of the women studied. Women's age, parity, and use of oral contraceptives
      were inversely associated with dysmenorrhea, and high stress increased the risk
      of dysmenorrhea. The effect sizes were generally modest to moderate, with odds
      ratios varying between 1 and 4. Family history of dysmenorrhea strongly increased
      its risk, with odds ratios between 3.8 and 20.7. Inconclusive evidence was found
      for modifiable factors such as cigarette smoking, diet, obesity, depression, and
      abuse. Dysmenorrhea is a significant symptom for a large proportion of women of
      reproductive age; however, severe pain limiting daily activities is less common.
      This review confirms that dysmenorrhea improves with increased age, parity, and
      use of oral contraceptives and is positively associated with stress and family
      history of dysmenorrhea. 

PMID- 24284872
TI  - Postnatal parental education for optimizing infant general health and parent
      infant relationships.
AB  - BACKGROUND: Many learning needs arise in the early postpartum period, and it is
      important to examine interventions used to educate new parents about caring for
      their newborns during this time. OBJECTIVES: The primary objective was to assess
      the effects of structured postnatal education delivered to an individual or group
      related to infant general health or care and parent-infant relationships. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 March 2013). SELECTION CRITERIA: We included randomized controlled
      trials of any structured postnatal education provided to individual parents or
      groups of parents within the first two months post-birth related to the health or
      care of an infant or parent-infant relationships. DATA COLLECTION AND ANALYSIS:
      Two review authors (JB, CTB) assessed trial quality and extracted data from
      published reports. MAIN RESULTS: Of the 27 trials (3949 mothers and 579 fathers)
      that met the inclusion criteria, only 15 (2922 mothers and 388 fathers) reported
      useable data. Educational interventions included: five on infant sleep
      enhancement, 12 on infant behaviour, three on general post-birth health, three on
      general infant care, and four on infant safety. Details of the randomization
      procedures, allocation concealment, blinding, and participant loss were often not
      reported. Of the outcomes analyzed, only 13 were measured similarly enough by
      more than one study to be combined in meta-analyses. Of these 13 meta-analyses,
      only four were found to have a low enough level of heterogeneity to provide an
      overall estimate of effect. Education about sleep enhancement resulted in a mean
      difference of 29 more night-time minutes of infant sleep in 24 hours at six weeks
      of age (95% confidence interval (CI) 18.53 to 39.73) than usual care. However, it
      had no significant effect on the mean difference in minutes of crying time in 24
      hours at six weeks and 12 weeks of age. Education related to infant behaviour
      increased maternal knowledge of infant behaviour by a mean difference of 2.85
      points (95% CI 1.78 to 3.91). AUTHORS' CONCLUSIONS: The benefits of educational
      programs to participants and their newborns remain unclear. Education related to
      sleep enhancement appears to increase infant sleep but appears to have no effect
      on infant crying time. Education about infant behaviour potentially enhances
      mothers' knowledge; however more and larger, well-designed studies are needed to
      confirm these findings.

PMID- 24284873
TI  - Generation of mutant mice by pronuclear injection of circular plasmid expressing
      Cas9 and single guided RNA.
AB  - CRISPR/Cas mediated genome editing has been successfully demonstrated in
      mammalian cells and further applications for generating mutant mice were reported
      by injecting humanized Cas9 (hCas) mRNA and single guide RNA into fertilized
      eggs. Here we inject the circular plasmids expressing hCas9 and sgRNA into mouse
      zygotes and obtained mutant mice within a month. When we targeted the Cetn1
      locus, 58.8% (10/17) of the pups carried the mutations and six of them were
      homozygously mutated. Co-injection of the plasmids targeting different loci
      resulted in the successful removal of the flanked region in two out of three
      mutant pups. The efficient mutagenesis was also observed at the Prm1 locus. Among
      the 46 offspring carrying CRISPR/Cas plasmid mediated mutations, only two of them
      carried the hCas9 transgene. The pronuclear injection of circular plasmid
      expressing hCas9/sgRNA complex is a rapid, simple, and reproducible method for
      targeted mutagenesis. 

PMID- 24284874
TI  - Newer gene editing technologies toward HIV gene therapy.
AB  - Despite the great success of highly active antiretroviral therapy (HAART) in
      ameliorating the course of HIV infection, alternative therapeutic approaches are
      being pursued because of practical problems associated with life-long therapy.
      The eradication of HIV in the so-called "Berlin patient" who received a bone
      marrow transplant from a CCR5-negative donor has rekindled interest in genome
      engineering strategies to achieve the same effect. Precise gene editing within
      the cells is now a realistic possibility with recent advances in understanding
      the DNA repair mechanisms, DNA interaction with transcription factors and
      bacterial defense mechanisms. Within the past few years, four novel technologies
      have emerged that can be engineered for recognition of specific DNA target
      sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN,
      and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch
      of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA,
      as opposed to the previous technologies that use DNA binding motifs of either
      zinc finger proteins or transcription activator-like effector molecules fused to
      an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA
      interference, which requires the continued presence of effector moieties to
      maintain gene silencing, the newer technologies allow permanent disruption of the
      targeted gene after a single treatment. Here, we review the applications,
      limitations and future prospects of novel gene-editing strategies for use as HIV
      therapy. 

PMID- 24284876
TI  - Large human outbreak of West Nile virus infection in north-eastern Italy in 2012.
AB  - Human cases of West Nile virus (WNV) disease have been reported in Italy since
      2008. So far, most cases have been identified in north-eastern Italy, where, in
      2012, the largest outbreak of WNV infection ever recorded in Italy occurred. Most
      cases of the 2012 outbreak were identified in the Veneto region, where a special
      surveillance plan for West Nile fever was in place. In this outbreak, 25 cases of
      West Nile neuroinvasive disease and 17 cases of fever were confirmed. In
      addition, 14 WNV RNA-positive blood donors were identified by screening of blood
      and organ donations and two cases of asymptomatic infection were diagnosed by
      active surveillance of subjects at risk of WNV exposure. Two cases of death due
      to WNND were reported. Molecular testing demonstrated the presence of WNV lineage
      1 in all WNV RNA-positive patients and, in 15 cases, infection by the novel
      Livenza strain was ascertained. Surveillance in other Italian regions notified
      one case of neuroinvasive disease in the south of Italy and two cases in
      Sardinia. Integrated surveillance for WNV infection remains a public health
      priority in Italy and vector control activities have been strengthened in areas
      of WNV circulation. 

PMID- 24284875
TI  - Human cytomegalovirus manipulation of latently infected cells.
AB  - Primary infection with human cytomegalovirus (HCMV) results in the establishment
      of a lifelong infection of the host which is aided by the ability of HCMV to
      undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic
      progenitor cells, resident in the bone marrow, with genome carriage and
      reactivation being restricted to the cells of the myeloid lineage. Until
      recently, HCMV latency has been considered to be relatively quiescent with the
      virus being maintained essentially as a "silent partner" until conditions are met
      that trigger reactivation. However, advances in techniques to study global
      changes in gene expression have begun to show that HCMV latency is a highly
      active process which involves expression of specific latency-associated viral
      gene products which orchestrate major changes in the latently infected cell.
      These changes are argued to help maintain latent infection and to modulate the
      cellular environment to the benefit of latent virus. In this review, we will
      discuss these new findings and how they impact not only on our understanding of
      the biology of HCMV latency but also how they could provide tantalising glimpses
      into mechanisms that could become targets for the clearance of latent HCMV. 

PMID- 24284877
TI  - HPV genotyping 9G membrane test.
AB  - The results of the genital human papillomavirus (HPV) detection in 439 cervical
      samples by cervical cytology were compared with sequencing analysis and a newly
      developed HPV genotyping 9G membrane test. The excellent sensitivity and
      specificity of the HPV genotyping 9G membrane test was assured by a signal to
      noise ratio of more than 300 and a target hybridization to non-target
      hybridization ratio of 300 ~ 400 at 25  degrees C. The final results can be
      obtained in 29 min by simple loading of the hybridization and washing solutions
      and scanning the membranes without any drying steps or special handling. The 100%
      identical results of the HPV genotyping 9G membrane test with sequencing results
      in 439 clinical samples demonstrate significant clinical application for this
      test. HPV genotyping 9G membrane tests can identify and discriminate five HR-HPV
      genotypes which are prevalent in almost 87% of cervical cancer cases. Its simple
      handling makes the HPV genotyping 9G membrane test a very convenient platform for
      accurate HPV genotyping. 

PMID- 24284879
TI  - Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more
      severe disease in lambs than virus grown in Vero cells.
AB  - Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in
      infants and young children. A small percentage of these individuals develop
      severe and even fatal disease. To better understand the pathogenesis of severe
      disease and develop therapies unique to the less-developed infant immune system,
      a model of infant disease is needed. The neonatal lamb pulmonary development and
      physiology is similar to that of infants, and sheep are susceptible to ovine,
      bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells
      has a truncated attachment G glycoprotein as compared to that grown in HEp-2
      cells. We hypothesized that the virus grown in HEp-2 cells would cause more
      severe clinical symptoms and cause more severe pathology. To confirm the
      hypothesis, lambs were inoculated simultaneously by two different delivery
      methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2
      grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease
      symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or
      nebulization inoculation had significantly higher levels of viral RNA in lungs as
      well as greater clinical disease including both gross and histopathologic lesions
      compared to lambs similarly inoculated with Vero-grown virus. Thus, our results
      provide convincing in vivo evidence for differences in viral infectivity that
      corroborate previous in vitro mechanistic studies demonstrating differences in
      the G glycoprotein expression by RSV grown in Vero cells. 

PMID- 24284878
TI  - Differential virulence and pathogenesis of West Nile viruses.
AB  - West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes
      and birds but that can also infect humans, horses, and other vertebrate animals.
      In most humans, WNV infection remains subclinical. However, 20%-40% of those
      infected may develop WNV disease, with symptoms ranging from fever to
      meningoencephalitis. A large variety of WNV strains have been described
      worldwide. Based on their genetic differences, they have been classified into
      eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago,
      Beasley et al. (2002) found that dramatic differences exist in the virulence and
      neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights
      on how WNV interacts with its hosts have recently been gained; the virus acts
      either at the periphery or on the central nervous system (CNS), and these
      observed differences could help explain the differential virulence and
      neurovirulence of WNV strains. This review aims to summarize the current state of
      knowledge on factors that trigger WNV dissemination and CNS invasion as well as
      on the inflammatory response and CNS damage induced by WNV. Moreover, we will
      discuss how WNV strains differentially interact with the innate immune system and
      CNS cells, thus influencing WNV pathogenesis. 

PMID- 24284881
TI  - Lipase-catalyzed process for biodiesel production: protein engineering and lipase
      production.
AB  - Biodiesel is an environment-friendly and renewable fuel produced by
      transesterification of various feedstocks. Although the lipase-catalyzed
      biodiesel production has many advantages over the conventional alkali catalyzed
      process, its industrial applications have been limited by high-cost and low
      stability of lipase enzymes. This review provides a general overview of the
      recent advances in lipase engineering, including both protein modification and
      production. Recent advances in biotechnology such as in protein engineering,
      recombinant methods and metabolic engineering have been employed but are yet to
      impact lipase engineering for cost-effective production of biodiesel. A summary
      of the current challenges and perspectives for potential solutions are also
      provided.

PMID- 24284880
TI  - Development of hematopoietic stem cell based gene therapy for HIV-1 infection:
      considerations for proof of concept studies and translation to standard medical
      practice.
AB  - Over the past 15 years we have been investigating an alternative approach to
      treating HIV-1/AIDS, based on the creation of a disease-resistant immune system
      through transplantation of autologous, gene-modified (HIV-1-resistant)
      hematopoietic stem and progenitor cells (GM-HSPC). We propose that the expression
      of selected RNA-based HIV-1 inhibitors in the CD4+ cells derived from GM-HSPC
      will protect them from HIV-1 infection and results in a sufficient immune
      repertoire to control HIV-1 viremia resulting in a functional cure for HIV
      1/AIDS. Additionally, it is possible that the subset of protected T cells will
      also be able to facilitate the immune-based elimination of latently infected
      cells if they can be activated to express viral antigens. Thus, a single dose of
      disease resistant GM-HSPC could provide an effective treatment for HIV-1+
      patients who require (or desire) an alternative to lifelong antiretroviral
      chemotherapy. We describe herein the results from several pilot clinical studies
      in HIV-1 patients and our strategies to develop second generation vectors and
      clinical strategies for HIV-1+ patients with malignancy who require ablative
      chemotherapy as part of treatment and others without malignancy. The important
      issues related to stem cell source, patient selection, conditioning regimen and
      post-infusion correlative studies become increasingly complex and are discussed
      herein. 

PMID- 24284882
TI  - An occupational exposure assessment for engineered nanoparticles used in
      semiconductor fabrication.
AB  - Engineered nanoparticles of alumina, amorphous silica, and ceria are used in
      semiconductor device fabrication during wafer polishing steps referred to as
      'chemical mechanical planarization' (CMP). Some metal oxide nanoparticles can
      impact the biological response of cells and organ systems and may cause adverse
      health effects; additional research is necessary to better understand potential
      risks from nanomaterial applications and occupational exposure scenarios. This
      study was conducted to assess potential airborne exposures to nanoparticles and
      agglomerates using direct-reading instruments and filter-based samples to
      characterize workplace aerosols by particle number, mass, size, composition, and
      morphology. Sampling was repeated for tasks in three work areas (fab, subfab,
      wastewater treatment) at a facility using engineered nanoparticles for CMP. Real
      time measurements were collected using a condensation particle counter (CPC),
      optical particle counter, and scanning mobility particle spectrometer (SMPS).
      Filter-based samples were analyzed for total mass or the respirable fraction, and
      for specific metals of interest. Additional air sample filters were analyzed by
      transmission electron microscopy with energy dispersive x-ray spectroscopy
      (TEM/EDX) for elemental identification and to provide data on particle size,
      morphology, and concentration. Peak concentrations measured on the CPC ranged
      from 1 to 16 particles per cubic centimeter (P cm(-3)) for background and from 4
      to 74 P cm(-3) during tasks sampled in the fab; from 1 to 60 P cm(-3) for
      background and from 3 to 84 P cm(-3) for tasks sampled in the subfab; and from
      1160 to 45 894 P cm(-3) for background and from 1710 to 45 519 P cm(-3) during
      wastewater treatment system filter change tasks. Significant variability was seen
      among the repeated task measurements and among background comparisons in each
      area. Several data analysis methods were used to compare each set of task and
      background measurements. Increased concentrations of respirable particles were
      identified for some tasks sampled in each work area, although of relatively low
      magnitude and inconsistently among repeated measurements for specific tasks.
      Measurements with a portable SMPS indicated that nanoparticle number
      concentrations (channels 11.5-115.5nm) increased above background levels by 3.2 P
      cm(-3) during CMP tool set-up in the fab area but were not elevated when changing
      filters for the CMP wastewater treatment system. All results from mass
      concentration analysis were below the limits of detection. Characterization by
      TEM/EDX identified structures containing the elements of interest (Al, Si),
      primarily as agglomerates or aggregates in the 100-1000nm size range. Although
      health-based occupational exposure limits have not been established for nanoscale
      alumina, silica, or ceria, the measured concentrations by number and mass were
      below currently proposed benchmarks or reference values for poorly soluble low
      toxicity nanoparticles. 

PMID- 24284883
TI  - Levels of cornell voltage and cornell product for predicting cardiovascular and
      stroke mortality and morbidity in the general Japanese population.
AB  - BACKGROUND: ECG-diagnosed left ventricular hypertrophy (LVH), the Cornell voltage
      (CV: >=2.8mV in males and >=2.0mV in females) or Cornell product (CP:
      >=244.0mV*ms), were selected in Western countries for their ability to diagnose
      anatomical LVH. METHODS AND RESULTS:  We aimed to elucidate the CV and CP values
      that were associated with a significantly increased risk of cardiovascular or
      stroke mortality and morbidity in a Japanese general population (n=10,172). In
      the receiver-operating curves analysis of CV and CP for predicting the risks, the
      area under the curve in females was greater than in males. In a quintile-based
      multivariate analysis that was performed separately for females and males, the
      mortality and morbidity risks of CV were significantly increased at the highest
      quintile of CV (>1.71mV) in females. In males, the mortality risk was
      significantly increased at the highest quintile of CV (>2.04mV). Additionally, in
      the parallel analysis of CP that included both males and females, the morbidity
      risk was significantly elevated in subjects with CP belonging to the 4th (158.7
      193.4mV*ms; hazard ratio=1.387) or 5th quintiles (>=193.5mV*ms; hazard
      ratio=1.507), compared with those with CP values within the lowest quintile
      (<101.9mV*ms). CONCLUSIONS: Cardiovascular and stroke risks may be elevated at
      lower levels of CV and CP in Japanese subjects, especially females. 

PMID- 24284885
TI  - Imaging molecular dynamics.

PMID- 24284884
TI  - Prediction of atrial fibrillation after off-pump coronary artery bypass grafting
      using preoperative total atrial conduction time determined on tissue Doppler
      imaging.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication of
      cardiac surgery and results in increased health-care utilization. This study
      identified new transthoracic echocardiographic predictors of POAF using an index
      of the total atrial conduction time derived on tissue Doppler imaging (PA-TDI
      duration) in patients undergoing off-pump coronary artery bypass grafting
      (OPCAB). METHODS AND RESULTS:  A total of 88 patients undergoing isolated OPCAB
      were enrolled. They were examined preoperatively on transthoracic
      echocardiography with tissue Doppler evaluations and monitored postoperatively
      with continuous electrocardiographic telemetry for 7 days. POAF occurred in 35
      patients (39.8%). Patients with POAF had a significantly longer duration of
      hospital stay than those without (44.9+/-6.2 vs. 37.3+/-3.3 days, P=0.04).
      Multivariate analysis showed that PA-TDI duration (odds ratio [OR], 1.11; 95%
      confidence interval [CI]: 1.06-1.16; P=0.0001) and left atrial volume index
      (LAVI; OR, 1.11; 95% CI: 1.02-1.20; P=0.01) were independent predictors of POAF.
      Moreover, PA-TDI duration was more reliable, given an area under the receiver
      operating characteristic curve of 0.85 (sensitivity, 74.3%; specificity, 86.8%).
      CONCLUSIONS: PA-TDI duration was an independent predictor of POAF following
      OPCAB. Awareness of risk of POAF may lead to the prevention of POAF, a rapid
      response to POAF, shortened hospital stay, and improved prognosis.  

PMID- 24284886
TI  - Nonimmune fetal hydrops and lysosomal storage disease: the finding of vacuolated
      lymphocytes in ascitic fluid in two cases.

PMID- 24284887
TI  - A case of isotretinoin-induced purpura annularis telangiectodes of Majocchi and
      review of substance-induced pigmented purpuric dermatosis.
AB  - IMPORTANCE Medications as well as chemical and food exposures have been causally
      linked to the development of pigmented purpuric dermatosis (PPD). We describe
      herein what is to our knowledge the first reported case of isotretinoin-induced
      PPD. OBSERVATIONS A woman in her 30s presented with purpura annularis
      telangiectodes of Majocchi on the lower extremities 2 months after initiating
      isotretinoin for the treatment of refractory nodulocystic acne. CONCLUSIONS AND
      RELEVANCE We believe isotretinoin was the most likely causative agent in this
      case because the lesions began after initiation of isotretinoin treatment and
      resolved shortly after its termination, and the pathologic findings were
      consistent with other described cases of drug-induced PPD. The lesions have
      continued to fade, and no new lesions have developed in a 3-month follow-up
      period. Drug-induced PPD is distinct from idiopathic PPD, and it is important to
      consider isotretinoin as a potential inciting agent. 

PMID- 24284889
TI  - Activated hepatic stellate cells promote hepatocellular carcinoma cell migration
      and invasion via the activation of FAK-MMP9 signaling.
AB  - Activated hepatic stellate cells (HSCs) are the major subtype of stromal cells in
      the liver tumor microenvironment which can promote the growth and migration of
      hepatocellular carcinoma (HCC) cells. However, the underlying mechanisms by which
      activated HSCs exert their oncogenic effects are not fully understood to date. In
      the present study, we investigated the number of activated HSCs and its
      clinicopathological significance in HCC and uncovered its correlation with focal
      adhesion kinase (FAK)-MMP9 signaling. A higher number of activated HSCs was
      associated with tumor invasion of the portal vein, advanced TNM stage and poorer
      tumor differentiation. The number of activated HSCs was positively correlated
      with the expression levels of p-FAK and MMP9 in HCC. Furthermore, we studied the
      effects of activated HSCs on the migration and invasion of HCC cells in vitro.
      Conditioned medium (CM) from activated HSCs or co-culture with activated HSCs
      significantly induced the migration and invasion of HCC cells. In addition,
      activation of FAK-MMP9 signaling in HCC was demonstrated in the presence of
      activated HSC-CM and of co-culture. Inhibition of FAK-MMP9 signaling in HCC cells
      with FAK short hairpin RNA (shRNA) abrogated the effects of activated HSCs on HCC
      cells. Taken together, our data suggest that activated HSCs in the tumor
      microenvironment promote HCC cell migration and invasion via activation of FAK
      MMP9 signaling.

PMID- 24284888
TI  - Axonal trafficking of NMNAT2 and its roles in axon growth and survival in vivo.
AB  - The NAD-synthesizing enzyme NMNAT2 is critical for axon survival in primary
      culture and its depletion may contribute to axon degeneration in a variety of
      neurodegenerative disorders. Here we discuss several recent reports from our
      laboratory that establish a critical role for NMNAT2 in axon growth in vivo in
      mice and shed light on the delivery and turnover of this survival factor in
      axons. In the absence of NMNAT2, axons fail to extend more than a short distance
      beyond the cell body during embryonic development, implying a requirement for
      NMNAT2 in axon maintenance even during development. Furthermore, we highlight
      findings regarding the bidirectional trafficking of NMNAT2 in axons on a vesicle
      population that undergoes fast axonal transport in primary culture neurites and
      in mouse sciatic nerve axons in vivo. Surprisingly, loss of vesicle association
      boosts the axon protective capacity of NMNAT2, an effect that is at least
      partially mediated by a longer protein half-life of cytosolic NMNAT2 variants.
      Analysis of wild-type and variant NMNAT2 in mouse sciatic nerves and Drosophila
      olfactory receptor neuron axons supports the existence of a similar mechanism in
      vivo, highlighting the potential for regulation of NMNAT2 stability and turnover
      as a mechanism to modulate axon degeneration in vivo. 

PMID- 24284890
TI  - Flexible transparent conducting composite films using a monolithically embedded
      AgNW electrode with robust performance stability.
AB  - We report on the performance of an all-in-one flexible hybrid conducting film
      employing a monolithically embedded AgNW transparent electrode and a high
      performance glass-fabric reinforced composite substrate (AgNW-GFRHybrimer film).
      Specifically, we perform in-depth investigations on the stability of the AgNW
      GFRHybrimer film against heat, thermal oxidation, and wet chemicals to
      demonstrate the potential of the hybrid conducting film as a robust electrode
      platform for thin-film optoelectronic devices. With the ease of large-area
      processability, smooth surface topography, and robust performance stability, the
      AgNW-GFRHybrimer film can be a promising platform for high-performance
      optoelectronic devices. 

PMID- 24284892
TI  - Wavelet analysis in ecology and epidemiology: impact of statistical tests.
AB  - Wavelet analysis is now frequently used to extract information from ecological
      and epidemiological time series. Statistical hypothesis tests are conducted on
      associated wavelet quantities to assess the likelihood that they are due to a
      random process. Such random processes represent null models and are generally
      based on synthetic data that share some statistical characteristics with the
      original time series. This allows the comparison of null statistics with those
      obtained from original time series. When creating synthetic datasets, different
      techniques of resampling result in different characteristics shared by the
      synthetic time series. Therefore, it becomes crucial to consider the impact of
      the resampling method on the results. We have addressed this point by comparing
      seven different statistical testing methods applied with different real and
      simulated data. Our results show that statistical assessment of periodic patterns
      is strongly affected by the choice of the resampling method, so two different
      resampling techniques could lead to two different conclusions about the same time
      series. Moreover, our results clearly show the inadequacy of resampling series
      generated by white noise and red noise that are nevertheless the methods
      currently used in the wide majority of wavelets applications. Our results
      highlight that the characteristics of a time series, namely its Fourier spectrum
      and autocorrelation, are important to consider when choosing the resampling
      technique. Results suggest that data-driven resampling methods should be used
      such as the hidden Markov model algorithm and the 'beta-surrogate' method. 

PMID- 24284891
TI  - Proton transfer reactions and hydrogen-bond networks in protein environments.
AB  - In protein environments, proton transfer reactions occur along polar or charged
      residues and isolated water molecules. These species consist of H-bond networks
      that serve as proton transfer pathways; therefore, thorough understanding of H
      bond energetics is essential when investigating proton transfer reactions in
      protein environments. When the pKa values (or proton affinity) of the H-bond
      donor and acceptor moieties are equal, significantly short, symmetric H-bonds can
      be formed between the two, and proton transfer reactions can occur in an
      efficient manner. However, such short, symmetric H-bonds are not necessarily
      stable when they are situated near the protein bulk surface, because the
      condition of matching pKa values is opposite to that required for the formation
      of strong salt bridges, which play a key role in protein-protein interactions. To
      satisfy the pKa matching condition and allow for proton transfer reactions,
      proteins often adjust the pKa via electron transfer reactions or H-bond pattern
      changes. In particular, when a symmetric H-bond is formed near the protein bulk
      surface as a result of one of these phenomena, its instability often results in
      breakage, leading to large changes in protein conformation. 

PMID- 24284893
TI  - Fish responses to flow velocity and turbulence in relation to size, sex and
      parasite load.
AB  - Riverine fish are subjected to heterogeneous flow velocities and turbulence and
      may use this to their advantage by selecting regions that balance energy
      expenditure for station holding while maximizing energy gain through feeding
      opportunities. This study investigated microhabitat selection by guppies Poecilia
      reticulata in terms of flow characteristics generated by hemisphere boulders in
      an open channel flume. Velocity and turbulence influenced the variation in
      swimming behaviour with respect to size, sex and parasite intensity. With
      increasing body length, fish swam further and more frequently between boulder
      regions. Larger guppies spent more time in the areas of high-velocity and low
      turbulence regions beside the boulders, whereas smaller guppies frequented the
      low-velocity and high-turbulence regions directly behind the boulders. Male
      guppies selected the regions of low velocity, indicating possible reduced
      swimming ability owing to hydrodynamic drag imposed by their fins. With
      increasing Gyrodactylus turnbulli burden, fish spent more time in regions with
      moderate velocity and lowest turbulent kinetic energy which were the most
      spatially and temporally homogeneous in terms of velocity and turbulence. These
      findings highlight the importance of heterogeneous flow conditions in river
      channel design owing to the behavioural variability within a species in response
      to velocity and turbulence. 

PMID- 24284894
TI  - Structure and mechanical properties of Octopus vulgaris suckers.
AB  - In this study, we investigate the morphology and mechanical features of Octopus
      vulgaris suckers, which may serve as a model for the creation of a new generation
      of attachment devices. Octopus suckers attach to a wide range of substrates in
      wet conditions, including rough surfaces. This amazing feature is made possible
      by the sucker's tissues, which are pliable to the substrate profile. Previous
      studies have described a peculiar internal structure that plays a fundamental
      role in the attachment and detachment processes of the sucker. In this work, we
      present a mechanical characterization of the tissues involved in the attachment
      process, which was performed using microindentation tests. We evaluated the
      elasticity modulus and viscoelastic parameters of the natural tissues (E ~ 10
      kPa) and measured the mechanical properties of some artificial materials that
      have previously been used in soft robotics. Such a comparison of biological
      prototypes and artificial material that mimics octopus-sucker tissue is crucial
      for the design of innovative artificial suction cups for use in wet environments.
      We conclude that the properties of the common elastomers that are generally used
      in soft robotics are quite dissimilar to the properties of biological suckers. 

PMID- 24284895
TI  - Non-lithographic patterning of phage-displayed peptides with wrinkled elastomers.
AB  - The development of controlled patterning of phage (viruses) could expand
      opportunities for both fundamental studies and creating various materials
      platforms. Inducing the elastomeric instability of PDMS film provides a non
      lithographic, tuneable, controlled method for generating micro/nanoscale wrinkle
      patterns. Phage display has emerged as a powerful method for selecting peptides
      that possess enhanced selectivity and binding affinity toward a variety of
      targets. In this report, we demonstrate the non-lithographic patterning of phage
      displayed peptides with wrinkled elastomers. Our results show that the phage
      displayed peptides can be patterned on specific locations in controlled and
      tuneable ways, be transferred to other substrates and induce the self-assembly of
      hybrid materials. We anticipate that these results could open up exciting
      opportunities in fundamental studies and in applications ranging from sensors,
      hybrid materials, self-assembly, surface and interface, to micro/nanoelectronics.

PMID- 24284896
TI  - Mechanically driven accumulation of microscale material at coupled solid-fluid
      interfaces in biological channels.
AB  - The accumulation of microscale materials at solid-fluid interfaces in biological
      channels is often the initial stage of certain growth processes, which are
      present in some forms of atherosclerosis. The objective of this work is to
      develop a relatively simple model for such accumulation, which researchers can
      use to qualitatively guide their analyses. Specifically, the approach is to
      construct rate equations for the accumulation at the solid-fluid interface as a
      function of the intensity of the shear stress. The accumulation of material
      subsequently reduces the cross-sectional area of the channel until the fluid
      induced shear stress at the solid-fluid interface reaches a critical value, which
      terminates the accumulation rate. Characteristics of the model are explored
      analytically and numerically. 

PMID- 24284897
TI  - Modelling and simulation of low-density lipoprotein transport through multi
      layered wall of an anatomically realistic carotid artery bifurcation.
AB  - A high concentration of low-density lipoprotein (LDL) is recognized as one of the
      principal risk factors for development of atherosclerosis. This paper reports on
      modelling and simulations of the coupled mass (LDL concentration) and momentum
      transport through the arterial lumen and the multi-layered arterial wall of an
      anatomically realistic carotid bifurcation. The mathematical model includes
      equations for conservation of mass, momentum and concentration, which take into
      account a porous layer structure, the biological membranes and reactive
      source/sink terms in different layers of the arterial wall, as proposed in Yang &
      Vafai (2006). A four-layer wall model of an arterial wall with constant thickness
      is introduced and initially tested on a simple cylinder geometry where realistic
      layer properties are specified. Comparative assessment with previously published
      results demonstrated proper implementation of the mathematical model. Excellent
      agreement for the velocity and LDL concentration distributions in the arterial
      lumen and in the artery wall are obtained. Then, an anatomically realistic
      carotid artery bifurcation is studied. This is the main novelty of the presented
      research. We find a strong dependence between underlying blood flow pattern (and
      consequently the wall shear stress distributions) and the uptake of the LDL
      concentration in the artery wall. The radial dependency of interactions between
      the diffusion, convection and chemical reactions within the multi-layered artery
      wall is crucial for accurate predictions of the LDL concentration in the media.
      It is shown that a four-layer wall model produced qualitatively good agreement
      with the experimental results of Meyer et al. (1996) in predicting levels of LDL
      within the media of a rabbit aorta under identical transmural pressure
      conditions. Finally, it is demonstrated that the adopted model represents a good
      initial platform for future numerical investigations of the initial stage of
      atherosclerosis for patient-specific geometries. 

PMID- 24284898
TI  - Optimal indolence: a normative microscopic approach to work and leisure.
AB  - Dividing limited time between work and leisure when both have their attractions
      is a common everyday decision. We provide a normative control-theoretic treatment
      of this decision that bridges economic and psychological accounts. We show how
      our framework applies to free-operant behavioural experiments in which subjects
      are required to work (depressing a lever) for sufficient total time (called the
      price) to receive a reward. When the microscopic benefit-of-leisure increases
      nonlinearly with duration, the model generates behaviour that qualitatively
      matches various microfeatures of subjects' choices, including the distribution of
      leisure bout durations as a function of the pay-off. We relate our model to
      traditional accounts by deriving macroscopic, molar, quantities from microscopic
      choices. 

PMID- 24284899
TI  - Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics
      in bone-resorbing osteoclasts.
AB  - The function of osteoclasts (OCs), multinucleated giant cells (MGCs) of the
      monocytic lineage, is bone resorption. To resorb bone, OCs form podosomes. These
      are actin-rich adhesive structures that pattern into rings that drive OC
      migration and into "sealing-zones" (SZs) that confine the resorption lacuna.
      Although changes in actin dynamics during podosome patterning have been
      documented, the mechanisms that regulate these changes are largely unknown. From
      human monocytic precursors, we differentiated MGCs that express OC degradation
      enzymes but are unable to resorb the mineral matrix. We demonstrated that,
      despite exhibiting bona fide podosomes, these cells presented dysfunctional SZs.
      We then performed two-step differential transcriptomic profiling of bone
      resorbing OCs versus nonresorbing MGCs to generate a list of genes implicated in
      bone resorption. From this list of candidate genes, we investigated the role of
      Rho/Rnd3. Using primary RhoE-deficient OCs, we demonstrated that RhoE is
      indispensable for OC migration and bone resorption by maintaining fast actin
      turnover in podosomes. We further showed that RhoE activates podosome component
      cofilin by inhibiting its Rock-mediated phosphorylation. We conclude that the
      RhoE-Rock-cofilin pathway, by promoting podosome dynamics and patterning, is
      central for OC migration, SZ formation, and, ultimately, bone resorption. 

PMID- 24284900
TI  - Prostaglandins temporally regulate cytoplasmic actin bundle formation during
      Drosophila oogenesis.
AB  - Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX)
      enzymes--regulate actin dynamics in cell culture and platelets, but their roles
      during development are largely unknown. Here we define a new role for Pxt, the
      Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal
      restriction of actin remodeling during oogenesis. PGs are required for actin
      filament bundle formation during stage 10B (S10B). In addition, loss of Pxt
      results in extensive early actin remodeling, including actin filaments and
      aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles
      exhibit similar structures at a low frequency. Hu li tai shao (Hts-RC) and Villin
      (Quail), an actin bundler, localize to all early actin structures, whereas
      Enabled (Ena), an actin elongation factor, preferentially localizes to those in
      pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt
      mutants. Furthermore, loss of Pxt results in reduced Ena localization to the
      sites of bundle formation during S10B. Together these data lead to a model in
      which PGs temporally regulate actin remodeling during Drosophila oogenesis by
      controlling Ena localization/activity, such that in S9, PG signaling inhibits,
      whereas at S10B, it promotes Ena-dependent actin remodeling.

PMID- 24284903
TI  - Real-time monitoring and control of soluble signaling factors enables enhanced
      progenitor cell outputs from human cord blood stem cell cultures.
AB  - Monitoring and control of primary cell cultures is challenging as they are
      heterogenous and dynamically complex systems. Feedback signaling proteins
      produced from off-target cell populations can accumulate, inhibiting the
      production of the desired cell populations. Although culture strategies have been
      developed to reduce feedback inhibition, they are typically optimized for a
      narrow range of process parameters and do not allow for a dynamically regulated
      response. Here we describe the development of a microbead-based process control
      system for the monitoring and control of endogenously produced signaling factors.
      This system uses quantum dot barcoded microbeads to assay endogenously produced
      signaling proteins in the culture media, allowing for the dynamic manipulation of
      protein concentrations. This monitoring system was incorporated into a fed-batch
      bioreactor to regulate the accumulation of TGF-beta1 in an umbilical cord blood
      cell expansion system. By maintaining the concentration of TGF-beta1 below an
      upper threshold throughout the culture, we demonstrate enhanced ex vivo expansion
      of hematopoietic progenitor cells at higher input cell densities and over longer
      culture periods. This study demonstrates the potential of a fully automated and
      integrated real-time control strategy in stem cell culture systems, and provides
      a powerful strategy to achieve highly regulated and intensified in vitro cell
      manufacturing systems.

PMID- 24284904
TI  - Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl
      successfully treated with ivermectin.
AB  - IMPORTANCE: There is a limited therapeutic armamentarium for recalcitrant cases
      of childhood rosacea. OBSERVATIONS: We report the case of a 12-year-old girl who
      presented with severe ocular and cutaneous rosacea unresponsive to oral
      doxycycline, oral isotretinoin, and topical tacrolimus. A biopsy specimen showed
      numerous mites within the folliculosebaceous unit. Treatment with a single dose
      of oral ivermectin achieved resolution of her symptoms. CONCLUSIONS AND
      RELEVANCE: The causative role of Demodex folliculorum should be considered in
      immunocompetent children with rosacea or rosacea-like refractory eruptions. In
      such cases, treatment with ivermectin can be beneficial.

PMID- 24284905
TI  - Note of appreciation to reviewers.
AB  - As we begin a new year, the Editorial Board, Associate and Assistant Editors and
      Editor-in-Chief of mAbs would like to thank the reviewers who contributed their
      insights and advice, as well as suggestions for improvement of manuscripts
      submitted for publication in mAbs volume 5, issues 1-6 (2013). The peer-review
      process involved the investment of substantial time and effort by the experts
      listed below, and we sincerely appreciate their valuable input on the selection
      of relevant, high-quality articles for mAbs readers. 

PMID- 24284901
TI  - Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin
      independent endocytic cargo proteins on endosomes.
AB  - Clathrin-independent endocytosis (CIE) mediates the internalization of many
      plasma membrane (PM) proteins involved in homeostasis, immune response, and
      signaling. CIE cargo molecules are internalized independent of clathrin, and
      dynamin, and modulated by the small G protein Arf6. After internalization the CIE
      cargo proteins either follow a default pathway of trafficking to lysosomes for
      degradation or follow a pathway where they are routed directly to the recycling
      endosomes for return to the PM. The selective endosomal sorting of molecules like
      CD44, CD98, and CD147, which are involved in cell-cell and cell-extracellular
      interactions, indicates that sorting mechanisms dictate the post-endocytic fate
      of CIE cargo proteins. In a recent study, we identified sorting signals that
      specify the endosomal trafficking of CIE cargo proteins and uncover a role for
      Hook1 as an endosomal cargo adaptor that routes CIE cargo to the recycling
      endosomes. Furthermore, we found that Hook1, microtubules, and Rab22a work in
      coordination to directly recycle the cargo and facilitate cell spreading. Here,
      we discuss our current view on the endosomal sorting of CIE cargo proteins and
      their molecular regulators. 

PMID- 24284906
TI  - Development and use of a high-fidelity simulator for fetal endotracheal balloon
      occlusion (FETO) insertion and removal.
AB  - Objectives The objective of this article is to describe the development of an
      anatomically accurate simulator in order to aid the training of a perinatal team
      in the insertion and removal of a fetal endoscopic tracheal occlusion (FETO)
      balloon in the management of prenatally diagnosed congenital diaphragmatic
      hernia. Methods An experienced perinatal team collaborated with a medical
      sculptor to design a fetal model for the FETO procedure. Measurements derived
      from 28-week fetal magnetic resonance imaging were used in the development of an
      anatomically precise simulated airway within a silicone rubber preterm fetal
      model. Clinician feedback was then used to guide multiple iterations of the model
      with serial improvements in the anatomic accuracy of the simulator airway.
      Results An appropriately sized preterm fetal mannequin with a high-fidelity
      airway was developed. The team used this model to develop surgical skills with
      balloon insertion, and removal, and to prepare the team for an integrated
      response to unanticipated delivery with the FETO balloon still in situ.
      Conclusions This fetal mannequin aided in the ability of a fetal therapy unit to
      offer the FETO procedure at their center for the first time. This model may be of
      benefit to other perinatal centers planning to offer this procedure.

PMID- 24284907
TI  - Effect of ripening stage on the development of the microbial community during
      spontaneous fermentation of green tomatoes.
AB  - BACKGROUND: Spontaneous fermentation of plant-derived material is mainly
      performed on a small scale, with the exception of fermented olives, cucumbers,
      sauerkraut and kimchi, which have met worldwide commercial significance. RESULTS:
      This study of spontaneous fermentation of green tomatoes at different stages of
      ripening revealed a significant effect on the growth kinetics of lactic acid
      bacteria and the final pH value. Leuconostoc mesenteroides dominated spontaneous
      fermentation when the initial pH value ranged from 3.8 to 4.8 whereas at higher
      pH values (4.9-5.4) it co-dominated with Leu. citreum and Lactobacillus casei.
      Application of RAPD-PCR and rep-PCR allowed differentiation at sub-species level,
      suggesting a microbial succession at that level accompanying the respective at
      species level. CONCLUSION: Ripening stage affected the development of the micro
      ecosystem through the growth of lactic acid bacteria and concomitant pH value
      reduction; however, the outcome of the fermentation was only marginally
      different.

PMID- 24284908
TI  - Online support for employed informal caregivers: psychosocial outcomes.
AB  - The overall objectives of this project were to evaluate whether psychosocial
      outcomes in employed family caregivers of people with chronic disease, who
      participate in online support, differ from nonactive participants and whether
      psychosocial outcomes differ based on the format of online group support. A
      randomized longitudinal design comparing two types of online support groups and
      nonactive participants, on the basis of three principal measures, was utilized.
      Eighty-six self-reported family caregivers of people with chronic disease, who
      spoke English and had Internet access, took part in the study. Subjects were
      randomly assigned to professionally facilitated/psychoeducational or
      moderated/peer-directed online support groups for a period of 12 weeks. The
      setting was a password-protected Web page housed on a university server.
      Independent variables were type of online support groups and level of
      participation; the dependent variables were depressive symptoms, caregiver
      burden, and caregiver quality of life. There were significant differences in
      depressive symptoms and quality of life among nonactive participants and either
      of the two intervention groups, but not between the two intervention groups.
      Results suggest that professionally facilitated/psychoeducational and
      moderated/peer-directed online support groups help reduce depressive symptoms and
      improve quality of life for those who actively participate and that both types of
      online support groups provided similar benefits. Men and minorities should be
      targeted in future caregiver research. 

PMID- 24284909
TI  - Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated
      immune cascade.
AB  - Thymic stromal lymphopoietin (TSLP) has emerged as a key initiator in Th2 immune
      responses, but the TSLP-driven immune cascade leading to Th2 initiation remains
      to be delineated. Here, by dissecting the cellular network triggered by mouse
      skin TSLP in vivo, we uncover that TSLP-promoted IL-4 induction in CD4(+) T cells
      in skin-draining lymph nodes is driven by an orchestrated 'DC-T-Baso-T' cascade,
      which represents a sequential cooperation of dendritic cells (DCs), CD4(+) T
      cells and basophils. Moreover, we reveal that TSLP-activated DCs prime naive
      CD4(+) T cells to produce IL-3 via OX40L signalling and demonstrate that the
      OX40L-IL-3 axis has a critical role in mediating basophil recruitment, CD4(+) T
      cell expansion and Th2 priming. These findings thus add novel insights into the
      cellular network and signal axis underlying the initiation of Th2 immune
      responses. 

PMID- 24284910
TI  - Inverse magnetocaloric and exchange bias effects in single crystalline
      La0.5Sr0.5MnO3 nanowires.
AB  - We report the first observation of inverse magnetocaloric effect (IMCE) in
      hydrothermally synthesized single crystalline La0.5Sr0.5MnO3 nanowires. The core
      of the nanowires is phase separated with the development of double exchange
      driven ferromagnetism (FM) in the antiferromagnetic (AFM) matrix, whereas the
      surface is found to be composed of disordered magnetic spins. The FM phase scales
      with the effective magnetic anisotropy, which is directly probed by transverse
      susceptibility experiments. The surface exhibits a glassy behavior and undergoes
      spin freezing, which manifests as a positive peak (T(L) ~ 42 K) in the magnetic
      entropy change (-DeltaS(M)) curves, thereby stabilizing the re-entrance of the
      conventional magnetocaloric effect. Precisely at T(L), the nanowires develop the
      exchange bias (EB) effect. Our results conclusively demonstrate that the mere
      coexistence of FM and AFM phases along with a disordered surface below their Neel
      temperature (T(N) ~ 210 K) does not trigger EB, but this develops only below the
      surface spin freezing temperature.

PMID- 24284912
TI  - Q fever outbreaks in Poland during 2005-2011.
AB  - BACKGROUND: Q fever is a health problem affecting humans and animals worldwide.
      In Poland, previous studies have pointed to 2 sources of outbreaks of the
      disease: the importation of infected animals and their products, and natural
      domestic foci. In the last decade, 5 outbreaks have occurred in cattle farms in
      south Poland in Malopolskie, Podkarpackie, Opolskie, and Silesian provinces. The
      aim of this study was to characterize the Q fever foci in Poland. MATERIAL AND
      METHODS: A total of 279 individuals were included. Levels of serum IgM and IgG
      antibodies to phase I and II C. burnetii antigens were assayed by indirect
      immunofluorescence method. Bacterial DNA from all specimens were detected with
      PCR with primer pairs specific to the htpAB-associated repetitive element, and
      amplicons were sequenced. RESULTS: Infection was recognized in 67 individuals out
      of 279 tested in all foci. Twenty-five individuals presented clinical symptoms of
      acute Q fever. DNA of C. burnetii was found in 8 human blood samples obtained
      from 3 farm workers and 5 family members. CONCLUSIONS: The described outbreaks
      demonstrate that the main source of human infections in Poland is infected
      cattle.

PMID- 24284913
TI  - Establishment of a green fluorescent protein tracing murine model focused on the
      functions of host components in necrosis repair and the niche of subcutaneously
      implanted glioma.
AB  - Due to progress in the research of glioma stem cells and the glioma niche,
      development of an animal model that facilitates the elucidation of the roles of
      the host tissue and cells is necessary. The aim of the present study was to
      develop a subcutaneous xenograft green fluorescent protein nude mouse model and
      use this model to analyze the roles of host cells in tumor necrosis repair.
      Tumors derived from the human glioma stem/progenitor cell line SU3 were
      subcutaneously implanted in green fluorescent protein nude mice. The implanted
      tumors were then passed from animal to animal for 10 generations. Finally,
      subcutaneous xenografts were assayed with traditional pathology,
      immunopathological techniques and fluorescence photography. For each generation,
      the tumorigenicity rate was 100%. Subcutaneous xenografts were rich in blood
      vessels, and necrotic and hemorrhagic foci, which highly expressed hypoxia
      inducible factor-1alpha, tumor necrosis factor, Ki-67, CD68 and CD11b. In the
      interstitial tissue, particularly in old hemorrhagic foci, there were numerous
      cells expressing green fluorescent protein, CD68 and CD11b. Green fluorescent
      protein nude mouse subcutaneous xenografts not only consistently maintained the
      high invasiveness and tumorigenicity of glioma stem/progenitor cells, but also
      consisted of a high concentration of tumor blood vessels and necrotic and
      hemorrhagic foci. Subcutaneous xenografts also expressed high levels of tumor
      microenvironment-related proteins and host-derived tumor interstitial molecules.
      The model has significant potential for further research on tumor tissue
      remodeling and the tumor microenvironment. 

PMID- 24284914
TI  - Antibodies to watch in 2014.
AB  - Since 2010, mAbs has documented the biopharmaceutical industry's progress in
      transitioning antibody therapeutics to first Phase 3 clinical studies and
      regulatory review, and its success at gaining first marketing approvals for
      antibody-based products. This installment of the "Antibodies to watch" series
      outlines events anticipated to occur between December 2013 and the end of 2014,
      including first regulatory actions on marketing applications for vedolizumab,
      siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and
      Factor VIII-Fc; and the submission of first marketing applications for up to five
      therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab).
      Antibody therapeutics in Phase 3 studies are described, with an emphasis on those
      with study completion dates in 2014, including antibodies targeting interleukin
      17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab),
      proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab,
      bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five
      antibodies with US Food and Drug Administration's Breakthrough Therapy
      designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab)
      are also discussed. 

PMID- 24284915
TI  - Functional reorganization of the corticospinal tract in a pediatric patient with
      an arteriovenous malformation.
AB  - Presurgical mapping in a pediatric patient diagnosed with arteriovenous
      malformation in the left hemisphere revealed a case of apparent functional
      reorganization of a white matter tract. Magnetoencephalography (MEG) was used to
      identify the motor fields following hand movement. As expected, motor field
      activity for the left hand was detected in the right hemisphere. Surprisingly,
      MEG activity was also detected in the right hemisphere following movement of the
      right hand. MEG activations served as seeds from which to launch diffusion tensor
      imaging tractography to delineate the corticospinal tracts (CSTs). Using the MEG
      activation for movement of the right hand, we delineated a tract in the right
      hemisphere. A tract corresponding to motor function for the left hand was also
      delineated in the right hemisphere. For comparison, the CSTs of the patient were
      launched from anatomical landmarks at the precentral gyrus, and were successfully
      delineated in each hemisphere. Our findings suggest that the functional
      delineation of white matter pathways may be more sensitive than anatomical
      delineation for identifying reorganization of the developing brain in response to
      a lesion. This study is, to our knowledge, the first description of a functional
      reorganization of an existing tract to serve as a CST in children. 

PMID- 24284916
TI  - Iodine isotopes species fingerprinting environmental conditions in surface water
      along the northeastern Atlantic Ocean.
AB  - Concentrations and species of iodine isotopes ((127)I and (129)I) provide vital
      information about iodine geochemistry, environmental conditions and water masses
      exchange in oceans. Despite extensive investigations of anthropogenic (129)I in
      the Arctic Ocean and the Nordic Seas, concentrations of the isotope in the
      Atlantic Ocean are, however, still unknown. We here present first data on (129)I
      and (127)I, and their species (iodide and iodate) in surface water transect along
      the northeastern Atlantic between 30 degrees  and 50 degrees N. The results show
      iodate as the predominant species in the analyzed marine waters for both (127)I
      and (129)I. Despite the rather constant ratios of (127)I(-)/(127)IO3(-), the
      (129)I(-)/(129)IO3(-) values reveal variations that apparently response to
      sources, environmental conditions and residence time. These findings provide a
      new tracer approach that will strongly enhance the application of anthropogenic
      (129)I in ocean environments and impact on climate at the ocean boundary layer. 

PMID- 24284917
TI  - [2n2pi + 2n2pi] cycloadditions: an alternative to forbidden [4pi + 4pi]
      processes. The case of nitrone dimerization.
AB  - A theoretical study based on (U)M06-2X/cc-pVTZ calculations has been used to
      investigate the [3 + 3] thermal dimerization of nitrones to 1,4,2,5
      dioxadiazinanes in both the gas phase and in dichloromethane solution.
      Calculations suggest that dimerization of nitrones takes place through a
      concerted mechanism involving a formal disallowed [4pi + 4pi] cycloaddition with
      a free energy barrier of 30.8 kcal mol(-1). The corresponding diradical and
      zwitterionic stepwise mechanisms have also been studied, but the located
      transition structures are kinetically disfavoured. An alternative mechanism
      through a five-membered ring intermediate formed by a classical [3 + 2] dipolar
      cycloaddition can also be discarded. The five-membered ring intermediate is
      unstable to cycloreversion and its isomerization to the final dioxadiazinane
      involves a high free energy barrier (68.6 kcal mol(-1)). Calculations also show
      that the dimerization process is slower in dichloromethane than in the gas phase
      owing to the larger polarity of nitrones and that inclusion of diffuse functions
      at the studied level does not modify the observed results. The apparently
      disfavoured [3 + 3] dimerization of nitrones can actually be explained as a
      bispseudopericyclic [2n2pi + 2n2pi] process in which the favourable FO
      interactions between the nitrone oxygen and the C=N pi* bypass the WH-forbidden
      process.

PMID- 24284918
TI  - Unmasking Brugada-type electrocardiogram on deep inspiration.
AB  - BACKGROUND:  Electrocardiogram (ECG) recorded at the upper intercostal lead
      positions is recommended as an additional diagnostic clue for Brugada syndrome
      (BrS), but similar recording conditions to unmask ECG signs have not been
      explored. METHODS AND RESULTS: We evaluated the diagnostic usefulness for
      unmasking ECG signs of BrS using recordings at the upper intercostal lead
      position, on deep inspiration and on standing. In 34 patients (mean age, 49+/-14
      years; 30 male) with diagnosed and suspected BrS, ECG type and ST-elevation in
      leads V1-V3 recorded at a higher position by 1 rib from the standard position
      (3ICS), and at standard lead positions (4ICS) on deep inspiration (DI test) and
      on standing (Stand test) were compared with the conventional lead positions
      (baseline). While type 1 ECG had been documented in 17 of 34 patients on at least
      1 occasion in the past, only 4 had the sign at baseline during the study. Twenty
      patients had type 1 on 3ICS recording, 18 on DI test, and 6 on Stand test. Among
      17 patients without previous documentation of spontaneous type 1, 7 had type 1 on
      3ICS recording, 6 on DI test, and 1 on Stand test. CONCLUSIONS: ECG recording on
      deep inspiration is useful to unmask diagnostic signs of BrS and has similar
      accuracy to 3ICS recording.  

PMID- 24284919
TI  - Progression of renal artery stenosis after renal denervation. Impact on 24-hour
      blood pressure.

PMID- 24284920
TI  - Histopathological examination by lung biopsy for the evaluation of operability
      and postoperative prognosis in patients with chronic thromboembolic pulmonary
      hypertension.
AB  - BACKGROUND: To evaluate the prognosis after pulmonary thromboendarterectomy (PTE)
      in patients with chronic thromboembolic pulmonary hypertension (CTEPH), a lung
      biopsy was performed in 34 patients with central CTEPH and in 7 patients with
      peripheral CTEPH during PTE. METHODS AND RESULTS: Postoperative prognosis was
      classified from A to E based on the postoperative hemodynamic parameters and
      clinical condition, and was compared with the index of occlusion (IOCTEPH), which
      indicates the degree of occlusion in the small pulmonary arteries. Criteria of (A
      E) were established only for central CTEPH. Category (A) corresponded to an
      IOCTEPH from 1.0 to 1.4, (B) from 1.5 to 1.7, (C) from 1.8 to 2.0, and (D) from
      2.1 to 2.4. One patient with an index of 3.0 was rated as (E). This patient had
      collateral vessels around the obstructed small pulmonary arteries and died
      postoperatively. In all 12 patients who underwent PTE after the criteria were
      established, postoperative hemodynamic parameters and clinical conditions were
      consistent with the IOCTEPH. One patient with a high degree of medial atrophy in
      their small pulmonary arteries died after PTE. CONCLUSIONS: These results
      indicate that a lung biopsy during PTE is useful for prognostication in patients
      with CTEPH.  

PMID- 24284921
TI  - P-pulmonale and the development of atrial fibrillation.
AB  - BACKGROUND: P wave >=0.25mV in inferior leads (P pulmonale) occurs in chronic
      lung diseases that underlie atrial fibrillation (AF). The purpose of this study
      was to elucidate the prognostic value of P pulmonale for development of AF.
      METHODS AND RESULTS: Digital analysis of 12-lead electrocardiogram (ECG) was
      conducted to enroll patients with P pulmonale from among a database containing
      308,391 ECGs. In a total of 591 patients (382 men; 56.4+/-14.8 years) with P
      pulmonale (follow-up, 46.7+/-65.6 months), AF occurred in 61 patients (AF group),
      but did not occur in 530 patients (non-AF group). Male gender was significantly
      more prevalent in the AF group than in the non-AF group (80.3% vs. 62.8%,
      P=0.0047). P-wave duration and PQ interval were significantly longer in the AF
      group than in the non-AF group (115.4+/-17.2ms vs. 107.0+/-17.2ms, P=0.0003 and
      166.3+/-23.9ms vs. 153.2+/-25.4ms, P=0.0001, respectively). In the total patient
      group, multivariate Cox proportional-hazards analysis confirmed that male gender
      (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.02-5.49; P=0.045), PQ
      interval >150ms (HR, 6.89; 95% CI: 2.39-29.15; P<0.0001), and P-wave axis <74
      degrees  (HR, 2.55; 95% CI: 1.20-5.41; P=0.016) were associated with AF
      development. In medication-free patients (n=400), only PQ interval >150ms (HR,
      9.26; 95% CI: 1.75-170.65; P=0.0055) was independently and significantly
      associated with AF development. CONCLUSIONS: PQ interval is the strongest
      stratifier for AF development in P pulmonale.  

PMID- 24284922
TI  - Giant saphenous vein graft aneurysm presenting as ST-elevation myocardial
      infarction.

PMID- 24284923
TI  - Expression of class II cytokine genes in children's skin.
AB  - Immune regulation of the skin plays an important role in susceptibility and
      development of illnesses. The aim of our study was to localise the interleukin
      (IL)-10 family of cytokines, in children's skin and to determine possible age
      related differences in the expression level. The mRNA expression level of IL10,
      IL19, IL20, IL22, IL24, IL26, IL28B, IL29 and their receptors IL10RA, IL10RB,
      IL20RA, IL20RB, IL22RA1, IL22RA2, IL28RA was compared in skin biopsies of
      children and adults and in childrens' skin cells by quantitative real-time PCR
      (qRT-PCR). Immunohistochemistry was performed to confirm the qRT-PCR findings. We
      found age-related differences in the expression of IL10RB, IL20, IL20RA, IL22RA1,
      IL22RA2, IL26 and IL28RA genes. Cell type-dependent expression of IL10 family
      cytokines was apparent in the skin. In addition to previously known differences
      in systemic immunological response of adults and children, the present results
      reveal differences in immune profile of adult and juvenile skin.

PMID- 24284925
TI  - Development of a tongue-piercing method for use with assistive technology.

PMID- 24284926
TI  - Birth defects in medically assisted reproduction pregnancies in the city of
      Barcelona.
AB  - OBJECTIVE: To assess the association between the use of medically assisted
      reproduction (MAR) and birth defects (BD) in newborns and terminations of
      pregnancy in pregnant women registered in Barcelona in the period 1992 to 2007.
      METHODS: We studied 1905 cases and 2722 controls in a retrospective population
      based case-control study. Cases comprised any newborn presenting at least one
      major BD, as well as any pregnancy terminated because of BD. Controls were
      newborns without BD. Exposure was MAR. Adjusted odds ratios (aOR) with 95%
      confidence intervals (CI) were calculated by means of logistic regression to
      assess the association. RESULTS: The MAR was demonstrated to be associated with
      BD, after adjusting for probable confounders (aOR = 1.8; 95% CI = 1.4 to 2.5).
      Regarding MAR modalities, this association was statistically significant only for
      assisted reproduction techniques (ART) (aOR = 2.7; 95% CI = 1.8 to 4.1). In the
      stratified analysis by structural BD categories, frequencies for all categories
      were increased after ART with the exception of head-face-neck-eye defects, none
      after artificial insemination, and digestive-abdominal wall defects in ovulation
      induction. CONCLUSIONS: This study demonstrated a strong association between ART
      and BD, with an almost threefold increased risk for overall BD after ART, as
      compared with natural conception. Increased associations were also observed for
      almost all structural BD categories.

PMID- 24284928
TI  - Phosphoglycerate kinase 1 promotes radioresistance in U251 human glioma cells.
AB  - Phosphoglycerate kinase 1 (PGK1) has been found to be increased in radioresistant
      astrocytomas. The present study was designed to investigate the potential role of
      PGK1 in the radioresistance in U251 human cells. Quantitative PCR and western
      blot analysis were performed to evaluate PGK1 expression for mRNA levels and
      protein levels, respectively. The short hairpin RNA (shRNA)-PGK1 and the high
      expression plasmids were transfected to radioresistant U251 cells (RR-U251 cells)
      or normal U251 cells using lipofectamineTM 2000. The cell viability was
      determined by MTT assay. The wound-healing assay (WHA) was used to evaluate cell
      migration ability. Cell invasion abilities were examined using a Transwell
      culture chamber system. Our results showed that the expression of PGK1 was
      significantly increased in RR-U251 cells compared to normal U251 cells. Following
      irradiation, the cell viability as well as the migration and invasion ability
      were significantly higher in RR-U251 cells compared with normal U251 cells.
      Downregulating PGK1 using shRNA induced a significantly downregulated cell
      viability and decreased migration and invasion ability, and overexpression of
      PGK1 contributed to upregulated cell viability and increased migration and
      invasion ability, both in RR-U251 cells and normal U251 cells. These findings
      suggest that PGK1 could promote radioresistance in U251 human cells. 

PMID- 24284936
TI  - Ultra scale-down characterization of the impact of conditioning methods for
      harvested cell broths on clarification by continuous centrifugation-Recovery of
      domain antibodies from rec E. coli.
AB  - The processing of harvested E. coli cell broths is examined where the expressed
      protein product has been released into the extracellular space. Pre-treatment
      methods such as freeze-thaw, flocculation, and homogenization are studied. The
      resultant suspensions are characterized in terms of the particle size
      distribution, sensitivity to shear stress, rheology and solids volume fraction,
      and, using ultra scale-down methods, the predicted ability to clarify the
      material using industrial scale continuous flow centrifugation. A key finding was
      the potential of flocculation methods both to aid the recovery of the particles
      and to cause the selective precipitation of soluble contaminants. While the
      flocculated material is severely affected by process shear stress, the impact on
      the very fine end of the size distribution is relatively minor and hence the
      predicted performance was only diminished to a small extent, for example, from
      99.9% to 99.7% clarification compared with 95% for autolysate and 65% for
      homogenate at equivalent centrifugation conditions. The lumped properties as
      represented by ultra scale-down centrifugation results were correlated with the
      basic properties affecting sedimentation including particle size distribution,
      suspension viscosity, and solids volume fraction. Grade efficiency relationships
      were used to allow for the particle and flow dynamics affecting capture in the
      centrifuge. The size distribution below a critical diameter dependent on the
      broth pre-treatment type was shown to be the main determining factor affecting
      the clarification achieved.

PMID- 24284937
TI  - Axillary and innominate artery cannulation during surgery of the thoracic aorta:
      a comparative study.
AB  - AIM: The aim of this paper was to compare hospital outcomes in patients
      undergoing elective surgery of the thoracic aorta using the right axillary artery
      (RAA) and the innominate artery (IA) as a cannulation site for cardiopulmonary
      bypass (CPB) arterial inflow. METHODS: Between September 2009 and October 2011,
      71 patients underwent elective aortic procedures with RAA (N.=27) and IA (N.=44)
      cannulation. Selection of RAA vs. IA was not randomized, but rather based on
      surgical judgment of best indication in each patient. Pre-, intra-, and
      postoperative variables were compared according to cannulation site. RESULTS:
      Preoperative comorbidities, underlying aortic pathology, and surgical procedures
      were similar in RAA and IA patients. Hospital mortality was 11.1% and 6.8% in RAA
      and IA patients, respectively (P=0.243). Overall, 4 brain infarctions occurred,
      all left sided (RAA: 3.7% vs. IA: 6.8%; P=0.508). One brachial plexus injury, and
      1 arterial dissection occurred in RAA group. No cannulation-related morbidity was
      observed in IA patients. Theoretical CPB flow could be reached in all patients,
      but resistances through the cannulation sites were more favourable in IA
      patients. CONCLUSION: RAA and IA were associated with similarly valid results.
      The choice between the two, based on the specific patient's characteristics, can
      improve outcomes after aortic surgery.

PMID- 24284938
TI  - Is intra-aortic balloon pump absolutely contraindicated in type A aortic
      dissection?
AB  - AIM: Circulatory failure following surgery for type A aortic dissection is
      frequent and associated with a high mortality rate. The intra-aortic balloon pump
      (IABP) is used to treat postcardiotomy cardiogenic shock but aortic dissection is
      traditionally a contraindication. In 10 patients we used IABP for severe
      cardiogenic shock following aortic dissection surgery, here we report on the
      short and midterm results. METHODS: From January 2000 to April 2008, among 151
      patients with type A aortic dissection 10 received a postoperative IABP. False
      lumen extension was limited to the ascending aorta for 3 patients, reached the
      arch for 1 and the descending aorta for 6. RESULTS: The device was placed in the
      operative room (7 patients), intensive care unit (2) and preoperatively (1). IABP
      was introduced percutaneously except for one who required surgical placement. The
      mean duration of IABP therapy was 3.8 days. Four patients died, but no death was
      directly related to IABP. Improvement in hemodynamics allowed 8 patients to be
      weaned off IABP. None suffered extension of the dissection. Two patients
      developed IABP-related complications. Six required extrarenal purification. Among
      the survivors, one died of a stroke at 38 months, 2 recovered the same quality of
      life and 3 had neurological sequelae without loss of autonomy. CONCLUSION: IABP
      should only be used as a salvage option in cases of severe cardiogenic shock
      following type A aortic dissection. No patient suffered device-related aortic
      rupture or extension of the dissection. High mortality and morbidity underline
      the gravity of cardiogenic shock in this setting.

PMID- 24284939
TI  - Current opinions about diagnosis and treatment strategy for aortic graft
      infections in The Netherlands.
AB  - AIM: Aortic graft infection (AGI) is a dreaded complication in vascular surgery.
      Research on AGI is hampered by its rarity combined with a broad range of clinical
      presentation in critically ill patients. This report aims to explore the various
      current opinions on the diagnosis and treatment of AGI. METHODS: A questionnaire
      was sent to all members of the Dutch Society of Vascular Surgery. Six weeks after
      the initial questionnaire a reminder was sent. A total of 306 questionnaires were
      sent. Data were analyzed for 124 vascular surgeons (VS) and 19 vascular surgeons
      in training (VT). Data analysis was performed in a descriptive manner. RESULTS:
      Total response rate was 51.3%, Response rate of the VS and VT combined was 47%.
      85% of the VS versus 58% of VT rely on computed tomography scanning (CT) scanning
      for diagnosing AGI. Positron emission tomography scanning with CT fusion was used
      by 40% of VS versus 58% of VT. Antibiotic treatment was started at the first
      suspicion of AGI by 52% of VS and 58% of VT. 13 different opinions were noted on
      total antibiotic duration. Extra-anatomic bypass (EAB) was used by and 42% of VT.
      In-situ reconstructions were used by 59% of VS versus % of VT. Venous
      reconstructions were the first reconstruction choice in 63% VS and 52% of VT.
      Antibiotic-bonded grafts were used by 17% of VS and 16% of VT. CONCLUSION: This
      survey shows highly mixed opinions about clinical diagnosis, diagnostic imaging,
      and treatment of AGI, reflecting available literature. Further research is
      therefore desperately needed. More research and development of treatment
      guidelines is needed to reach uniformity and consensus for patients with infected
      vascular grafts.

PMID- 24284940
TI  - TAArget versus EndoFit thoracic stent-grafts in thoracic endovascular aortic
      repair: a retrospective comparison of early and mid-term results in a single
      center.
AB  - Aim: Aim of the study was to compare our early and mid-term results using EndoFit
      and TAArget thoracic stent-grafts in thoracic endovascular aortic repair (TEVAR).
      Methods: We retrospectively reviewed 169 consecutive TEVAR cases (69.1+/-8.9
      years) performed using the EndoFit or TAArget thoracic stent-grafts from December
      2005 to January 2011 in our single center. Debranching procedures were needed in
      111 (65.7%) cases before TEVAR. 87 (51.5%) patients who received EndoFit stent
      graft between December 2005 and December 2007 were entered into Group A while the
      other 82 (48.5%) patients treated from January 2008 to January 2011 using TAArget
      stent-graft into Group B. Results: The technical success rate was 100% in both
      groups. 111 (65.7%) cases had 6 different debranching procedures prior to TEVAR
      to extend the proximal or distal landing zone. In group A, 5 cases had
      intraoperative proximal type I endoleak, while no occurrence in group B. The
      overall 30-day mortality rate was 5.3% (9/169), with statistical difference
      (Group A: 9.2%, 8/87 versus Group B: 1.2%, 1/82; P=0.049). Neurological
      complications occurred in 8 (4.7%) patients, all of the cases were in group A
      (8/87). There were 10 (6.3%) deaths recorded during the average of 29.0 months
      (range 15-42) follow-up period, all of the patients were in group A (Group A:
      12.7%, 10/79 versus Group B: 0%, 0/81; P=0.003), no death was related to the
      aneurysm or the stent-graft. In Group A, 2 cases had post-TEVAR proximal type I
      endoleak. Conclusion: Better clinical outcomes are highly dependent on
      accumulated learning curve and improved newer-generation devices and delivery
      systems. The second generation device TAArget's new featuring uniform external
      fixation and TTTM Tortuous tracker delivery system allow better external fixation
      and precise deployment.

PMID- 24284941
TI  - High-throughput nanofabrication of infra-red and chiral metamaterials using
      nanospherical-lens lithography.
AB  - Various infra-red and planar chiral metamaterials were fabricated using the
      modified Nanospherical-Lens Lithography. By replacing the light source with a
      hand-held ultraviolet lamp, its asymmetric light emission pattern produces the
      elliptical-shaped photoresist holes after passing through the spheres. The long
      axis of the ellipse is parallel to the lamp direction. The fabricated ellipse
      arrays exhibit localized surface plasmon resonance in mid-infra-red and are ideal
      platforms for surface enhanced infra-red absorption (SEIRA). We also demonstrate
      a way to design and fabricate complicated patterns by tuning parameters in each
      exposure step. This method is both high-throughput and low-cost, which is a
      powerful tool for future infra-red metamaterials applications. 

PMID- 24284942
TI  - Sun-induced pustular dermatosis of the scalp - a new variant of erosive pustular
      dermatosis of the scalp?

PMID- 24284943
TI  - TRAF1 is a critical regulator of cerebral ischaemia-reperfusion injury and
      neuronal death.
AB  - Stroke is a leading global cause of mortality and disability. Less than 5% of
      patients are able to receive tissue plasminogen activator thrombolysis within the
      necessary timeframe. Focusing on the process of neuronal apoptosis in the
      penumbra, which lasts from hours to days after ischaemia, appears to be
      promising. Here we report that tumour necrosis factor receptor-associated factor
      1 (TRAF1) expression is markedly induced in wild-type mice 6 h after stroke
      onset. Using genetic approaches, we demonstrate that increased neuronal TRAF1
      leads to elevated neuronal death and enlarged ischaemic lesions, whereas TRAF1
      deficiency is neuroprotective. In addition, TRAF1-mediated neuroapoptosis
      correlates with the activation of the JNK pro-death pathway and inhibition of the
      Akt cell survival pathway. Finally, TRAF1 is found to exert pro-apoptotic effects
      via direct interaction with ASK1. Thus, ASK1 positively and negatively regulates
      the JNK and Akt signalling pathways, respectively. Targeting the TRAF1/ASK1
      pathway may provide feasible therapies for stroke long after onset.

PMID- 24284944
TI  - Role of pepsin and pepsinogen: linking laryngopharyngeal reflux with otitis media
      with effusion in children.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the relationship between laryngopharyngeal
      reflux (LPR) represented by pepsin and pepsinogen, and pathogenesis of otitis
      media with effusion (OME). STUDY DESIGN: Prospective case-control study. METHODS:
      Children with OME who required adenoidectomy and tympanostomy/tympanostomy tubes
      placement were enrolled in OME group, whereas children with adenoid hypertrophy
      (AH) who required adenoidectomy and individuals who required cochlear
      implantation (CI) were enrolled in AH and CI groups, respectively. Pepsinogen
      mRNA and protein levels were assessed by real-time fluorescence-based
      quantitative polymerase chain reaction and immunohistochemistry in adenoid
      specimens from the OME and AH groups. Pepsin and pepsinogen concentrations were
      evaluated by enzyme-linked immunosorbent assay in middle ear fluid and plasma
      from the OME and CI groups. RESULTS: The levels of pepsinogen protein expressed
      in cytoplasm of epithelial cells and clearance under epithelial cells in adenoid
      specimens from the OME group were significantly higher than those in the AH
      group. Furthermore, the concentrations of pepsin and pepsinogen in the OME group
      were 51.93+/-11.58 ng/mL and 728+/-342.6 ng/mL, respectively, which were
      significantly higher than those in the CI group (P<.001). In addition, the
      concentrations of pepsin in dry ears were significantly lower than those in
      serous and mucus ears in the OME group (F=22.77, P<.001).Finally, the
      concentration of pepsinogen in middle ear effusion was positively correlated with
      the expression intensity of pepsinogen protein in cytoplasm of epithelial cells
      (r=0.73, P<.05) in the OME group. CONCLUSIONS: Pepsin and pepsinogen in middle
      ear effusion are probably caused by LPR and may be involved in the pathogenesis
      of OME. LEVEL OF EVIDENCE: 3b.

PMID- 24284945
TI  - Diagnostic accuracy of an iPhone DICOM viewer for the interpretation of magnetic
      resonance imaging of the knee.
AB  - OBJECTIVE: To evaluate the diagnostic performance of viewing magnetic resonance
      (MR) images on a handheld mobile device compared with a conventional radiology
      workstation for the diagnosis of intra-articular knee pathology. DESIGN:
      Prospective comparison study. SETTING: Tertiary care center. PATIENTS: Fifty
      consecutive subjects who had MR imaging of the knee followed by knee arthroscopy
      were prospectively evaluated. INTERVENTIONS: Two musculoskeletal radiologists
      independently reviewed each MR study using 2 different viewers: the OsiriX DICOM
      viewer software on an Apple iPhone 3GS device and eFilm Workstation software on a
      conventional picture archiving and communications system workstation. MAIN
      OUTCOME MEASURES: Sensitivity and specificity of the iPhone and workstation
      interpretations was performed using knee arthroscopy as the reference standard.
      Intraobserver concordance and agreement between the iPhone and workstation
      interpretations were determined. RESULTS: There was no statistically significant
      difference between the 2 devices for each paired comparison of diagnostic
      performance. For the iPhone interpretations, sensitivity ranged from 77% (13 of
      17) for the lateral meniscus to 100% (17 of 17) for the anterior cruciate
      ligament. Specificity ranged from 74% (14 of 19) for cartilage to 100% (50 of 50)
      for the posterior cruciate ligament. There was a very high level of interobserver
      and intraobserver agreement between devices and readers. The iPhone reads took
      longer than the corresponding workstation reads, with a significant mean
      difference between the iPhone and workstation reads of 3.98 minutes (P < 0.001).
      CONCLUSIONS: The diagnostic performance of interpreting MR images on a handheld
      mobile device for the assessment of intra-articular knee pathology is similar to
      that of a conventional radiology workstation, however, requires a longer viewing
      time. CLINICAL RELEVANCE: Timely and accurate interpretation of complex medical
      images using mobile device solutions could result in new workflow efficiencies
      and ultimately improve patient care.

PMID- 24284946
TI  - Tennis-related injuries treated in United States emergency departments, 1990 to
      2011.
AB  - OBJECTIVE: To analyze the patterns and causes of tennis-related injuries using,
      for the first time, a nationally representative data set. DESIGN: A retrospective
      cohort analysis was performed using the National Electronic Injury Surveillance
      System database. SETTING: All tennis-related injuries treated in US emergency
      departments (EDs) from 1990 to 2011 were analyzed. PATIENTS: During the study
      period, an estimated 492,002 (95% confidence interval, 364,668-619,336)
      individuals, aged 5 to 94 years, presented to US EDs for tennis-related injuries.
      ASSESSMENT OF RISK FACTORS: Independent variables included patient age and
      gender, mechanism of injury, and location of injury event. MAIN OUTCOME MEASURES:
      Outcome variables included injury diagnosis, body region injured, disposition
      from ED, and involvement of the net. RESULTS: Most injuries were sustained by a
      nonspecific mechanism during play (37.9%) and occurred at a sport or recreation
      facility (83.4%). Children aged 5 to 18 years had a higher mean injury rate than
      adults older than 19 years. The most commonly injured body regions were the lower
      extremities (42.2%) and upper extremities (26.7%). Sprains or strains (44.1%)
      were the most common type of injury. The number of tennis-related injuries
      decreased by 41.4% during the years 1990 to 2011, and the tennis-related injury
      rates decreased by more than 45% during the study period. Among the 3.4% of
      patients who were admitted to the hospital, two-thirds (65.6%) involved patients
      56 years of age or older. CONCLUSIONS: Despite the decrease in tennis-related
      injuries, the growing popularity of this sport warrants increased efforts to
      prevent injuries, especially among child and older adult participants.

PMID- 24284947
TI  - An alternative to the balance error scoring system: using a low-cost balance
      board to improve the validity/reliability of sports-related concussion balance
      testing.
AB  - OBJECTIVE: Recent guidelines advocate sports medicine professionals to use
      balance tests to assess sensorimotor status in the management of concussions. The
      present study sought to determine whether a low-cost balance board could provide
      a valid, reliable, and objective means of performing this balance testing.
      DESIGN: Criterion validity testing relative to a gold standard and 7 day test
      retest reliability. SETTING: University biomechanics laboratory. PARTICIPANTS:
      Thirty healthy young adults. ASSESSMENT OF RISK FACTORS: Balance ability was
      assessed on 2 days separated by 1 week using (1) a gold standard measure (ie,
      scientific grade force plate), (2) a low-cost Nintendo Wii Balance Board (WBB),
      and (3) the Balance Error Scoring System (BESS). MAIN OUTCOME MEASURES: Validity
      of the WBB center of pressure path length and BESS scores were determined
      relative to the force plate data. Test-retest reliability was established based
      on intraclass correlation coefficients. RESULTS: Composite scores for the WBB had
      excellent validity (r = 0.99) and test-retest reliability (R = 0.88). Both the
      validity (r = 0.10-0.52) and test-retest reliability (r = 0.61-0.78) were lower
      for the BESS. CONCLUSIONS: These findings demonstrate that a low-cost balance
      board can provide improved balance testing accuracy/reliability compared with the
      BESS. CLINICAL RELEVANCE: This approach provides a potentially more
      valid/reliable, yet affordable, means of assessing sports-related concussion
      compared with current methods.

PMID- 24284948
TI  - The impact of sex and knee injury history on jump-landing patterns in collegiate
      athletes: a clinical evaluation.
AB  - OBJECTIVE: To determine whether jump-landing patterns, as assessed by the Landing
      Error Scoring System (LESS), differ based on sex and knee injury history. DESIGN:
      Cross-sectional. SETTING: College. PARTICIPANTS: Two hundred fifteen
      intercollegiate athletes were grouped by sex (male = 116 and female = 99) and
      self-reported knee injury history (no = 148, mild = 31, and severe = 36).
      INTERVENTIONS: Participants performed 3 trials of a standardized jump-landing
      task that were videotaped and later scored using the LESS. MAIN OUTCOME MEASURES:
      Overall, individual item, sagittal total error, and frontal total error scores of
      the LESS. RESULTS: An interaction effect was reported for trunk flexion at
      initial ground contact. Main effects for sex indicated that males demonstrated
      more at-risk landing movement patterns on the sagittal plane (ie, limited trunk,
      knee and hip flexion at initial contact, and limited hip flexion throughout the
      landing), whereas females demonstrated more at-risk landing movement patterns on
      the frontal plane (ie, knee valgus at initial ground contact and maximum knee
      flexion, and more frontal plane movement throughout the landing). No main effects
      were reported for injury history. CONCLUSIONS: Jump-landing patterns seem to be
      impacted by sex but not knee injury history. Findings related to sex differences
      corroborate with previous laboratory-based investigations. Furthermore, findings
      support the clinical use of the LESS to screen for individuals who may be at risk
      for a lower extremity injury. Future studies should further investigate the
      clinical utility of the LESS, particularly its ability to predict lower extremity
      injuries.

PMID- 24284949
TI  - Mechanisms of injury for concussions in university football, ice hockey, and
      soccer.
AB  - OBJECTIVE: To examine the mechanisms of injury for concussions in university
      football, ice hockey, and soccer. DESIGN: Prospective cohort design. SETTING:
      McGill University Sport Medicine Clinic. PARTICIPANTS: Male and female athletes
      participating in varsity football, ice hockey, and soccer. MAIN OUTCOME MEASURES:
      Athletes were followed prospectively over a 10-year period to determine the
      mechanisms of injury for concussions and whether contact with certain areas of
      the body or individual variables predisposed to longer recovery from concussions.
      For soccer, data were collected on whether concussions occurred while attempting
      to head the ball. RESULTS: There were 226 concussions in 170 athletes over the
      study period. The side/temporal area of the head or helmet was the most common
      area to be struck resulting in concussion in all 3 sports. Contact from another
      player's head or helmet was the most probable mechanism in football and soccer.
      In hockey, concussion impacts were more likely to occur from contact with another
      body part or object rather than another head/helmet. Differences in mechanisms of
      injuries were found between males and females in soccer and ice hockey. Athletes
      with multiple concussions took longer to return to play with each subsequent
      concussion. Half of the concussions in soccer were related to attempting to head
      the soccer ball. CONCLUSIONS: The side of the head or helmet was the most common
      area to be struck resulting in concussion in all 3 sports. In ice hockey and
      soccer, there are differences in the mechanisms of injury for males and females
      within the same sport.

PMID- 24284950
TI  - Jejunal tackle: a case report of complete jejunal transection in rugby union.
AB  - Jejunal perforation as a result of blunt abdominal trauma during sport is
      particularly rare. We are aware of 6 reported cases of jejunal perforation in
      sport: 1 in hockey, 2 in football (soccer), and 3 in American football. This
      report presents the case of a 25-year-old professional rugby union player, who
      presented to an "After Hours" general practice clinic with increasing central
      abdominal and epigastric pain after a heavy tackle during an international match
      in New Zealand. Despite suffering complete jejunal transection, the patient
      continued to play on, only presenting to an After Hours general practice clinic 3
      hours after the injury. The case demonstrates the remarkable physiological
      resilience of professional rugby players and acts as a reminder to maintain a
      high degree of suspicion for small bowel injury despite normal vital signs in
      healthy young patients with abdominal pain secondary to blunt trauma.

PMID- 24284951
TI  - Analysis of weight change and Borg rating of perceived exertion as measurements
      of runner health and safety during a 6-day, multistage, remote ultramarathon.
AB  - OBJECTIVE: To determine the feasibility of using weight change and Borg score as
      tools for monitoring runner health and safety during a multistage, remote
      ultramarathon. DESIGN: Observational cohort study of feasibility on nonblinded
      event participants. SETTING: Six-day, multistage, remote ultramarathon in Utah.
      PARTICIPANTS: Twenty-seven athletes in the 2012 Desert R.A.T.S. (Race Across the
      Sand) ultramarathon. ASSESSMENT OF RISK FACTORS: Participant weight, health
      conditions that limited race participation, such as fatigue or exhaustion, and
      Borg score were reviewed. MAIN OUTCOME MEASURES: Inability to complete a stage of
      the race (Did Not Finish status) or development of a clinically significant
      health condition during the race. Potential prognostic risk factors, such as a
      high Borg score and weight loss, were analyzed. RESULTS: An overall decrease in
      weight was observed over the course of the event. Median percent weight changes
      were losses of 2.96% (day 1), 7.42% (day 2), 2.21% (day 4), and 3.35% (day 6).
      There was no statistically significant difference in percent weight change
      between the 14 runners who finished the race and the 13 runners who did not
      finish the race (U = 73; z = 0.189; P = 0.85). Runners' ability to complete the
      race was related to the development of adverse health conditions (P = 0.004).
      Median Borg scores reported were 15 (day 1), 17 (day 2), 13 (day 3), 16 (day 4),
      and 15 (day 6). Only 2 racers who finished the entire event without adverse
      events ever gave a Borg score of >= 18. CONCLUSIONS: The feasibility of weight
      change as a tool for monitoring runner health and safety in this setting is
      limited, but the Borg rating of perceived exertion warrants further study as a
      potential field expedient tool for monitoring runner health and safety during a
      multiday, remote ultramarathon.

PMID- 24284952
TI  - Medium-term and long-term outcomes of interventions for primary psoas
      tendinopathy.
AB  - OBJECTIVE: To assess medium- and long-term outcomes of psoas tendinopathy to
      psoas tenotomy and image-guided steroid injections. DESIGN: This is a 14-year
      retrospective case-control study to identify the efficacy of psoas tenotomy and
      image-guided steroid injections. SETTING: This study was undertaken in a
      secondary care setting. PATIENTS: Patients with confirmed psoas tendinopathy were
      followed up by postal questionnaire, which included a nonarthritic hip score
      (NAHS) and a study patient satisfaction questionnaire. INTERVENTIONS: Patients
      underwent image-guided steroid injections. Depending on the analgesic or
      symptomatic relief, some patients proceeded to psoas tenotomy. MAIN OUTCOME
      MEASURES: Response to steroid injection. Pain relief and symptomatic relief after
      the surgery. RESULTS: Twenty-three patients were reviewed with a 70% follow-up
      over a time of 49 months for surgery (range, 13-144 months) and 77 months for
      injection (range, 14-160 months). Eight patients had a lasting response to
      injection and required no further intervention, and 15 patients proceeded to
      psoas tenotomy using a medial Ludloff approach. The average NAHS scores after the
      surgery and injection were 66.15 and 76.08, respectively. Ten patients reported
      pain relief after their tenotomy, and 5 patients reported no change in pain. All
      8 patients, who only underwent injection, reported lasting pain relief.
      CONCLUSIONS: Local steroid injections can provide long-term relief for patients
      presenting with psoas tendinopathy. For those patients with only temporary relief
      from injection, psoas tenotomy can provide good long-term pain relief.

PMID- 24284953
TI  - Quantification of the dielectric constant of single non-spherical nanoparticles
      from polarization forces: eccentricity effects.
AB  - We analyze by means of finite-element numerical calculations the polarization
      force between a sharp conducting tip and a non-spherical uncharged dielectric
      nanoparticle with the objective of quantifying its dielectric constant from
      electrostatic force microscopy (EFM) measurements. We show that for an oblate
      spheroid nanoparticle of given height the strength of the polarization force
      acting on the tip depends linearly on the eccentricity, e, of the nanoparticle in
      the small eccentricity and low dielectric constant regimes (1 < e < 2 and 1 <
      epsilon(r) < 10), while for higher eccentricities (e > 2) the dependence is sub
      linear and finally becomes independent of e for very large eccentricities (e >
      30). These results imply that a precise account of the nanoparticle shape is
      required to quantify EFM data and obtain the dielectric constants of non
      spherical dielectric nanoparticles. Experimental results obtained on polystyrene,
      silicon dioxide and aluminum oxide nanoparticles and on single viruses are used
      to illustrate the main findings.

PMID- 24284954
TI  - Strengthening the HIV cascade to ensure an effective future ART response in sub
      Saharan Africa.
AB  - Timely linkage to antiretroviral therapy (ART) care is critical for reducing HIV
      related morbidity, mortality and transmission. Studies investigating
      interventions to improve linkage to, and retention in, pre-ART care in sub
      Saharan Africa were reviewed. Certain interventions used to overcome economic
      barriers for ART-patients (i.e. integration of services, medical and food
      incentives, intensified counselling and peer support) have also shown favourable
      results in the pre-ART period. A combined package of interventions found to be
      effective in the pre-ART and ART period might be effective for reducing attrition
      in both periods. Further operational research in this area is needed to identify
      local solutions.

PMID- 24284955
TI  - Detection of IgG in sera of patients with schistosomiasis japonica by developing
      magnetic affinity enzyme-linked immunoassay based on recombinant 14-3-3 protein.
AB  - BACKGROUND: Low intensity of Schistosoma infection is the current status in China
      after long time treatment with praziquantel, therefore more sensitive diagnostic
      methods are required now. In this study, a magnetic affinity enzyme-linked
      immunoassay (MEIA) based on the signal transduction protein 14-3-3 of Schistosoma
      japonicum (Sj14-3-3), was developed for detecting schistosomiasis. METHODS: Sera
      of infected BALB/c mice were collected and analyzed with MEIA and ELISA. Both
      MEIA and ELISA based on Sj14-3-3 were further used to detect serum IgG in
      patients. Sera from 58 schistosomiasis-related patients with low-intensity
      infection, and 30 non-endemic negative controls, were collected to assess the
      assay. Six sera from paragonimiasis patients were used to analysis cross
      reactions. RESULTS: Compared with ELISA, MEIA has a higher ratio of the mean
      positive value to the mean negative value (P/N) at the same dilution ratio in
      infected mice (3.71 vs 2.45). Similar results were observed in humans, higher P/N
      of MEIA compared to ELISA (3.57 vs 2.68). There was no cross-reaction with the
      sera of paragonimiasis patients detected by both MEIA and ELISA. CONCLUSIONS: Our
      studies suggested that MEIA based on recombinant Sj14-3-3 protein (rSj14-3-3) had
      the potential for the diagnosis of schistosomiasis.

PMID- 24284956
TI  - Glial cell line-derived neurotrophic factor-secreting human neural progenitors
      show long-term survival, maturation into astrocytes, and no tumor formation
      following transplantation into the spinal cord of immunocompromised rats.
AB  - Human neural progenitor cells (hNPCs) derived from the fetal cortex can be
      expanded in vitro and genetically modified through lentiviral transduction to
      secrete growth factors shown to have a neurotrophic effect in animal models of
      neurological disease. hNPCs survive and mature following transplantation into the
      central nervous system of large and small animals including the rat model of
      amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express
      glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months)
      following transplantation into the spinal cord of athymic nude rats and continue
      to secrete GDNF. Cell proliferation declined while the number of astrocytes
      increased, suggesting final maturation of the cells over time in vivo. Together
      these data show that GDNF-producing hNPCs may be useful as a source of cells for
      long-term delivery of both astrocytes and GDNF to the damaged central nervous
      system. 

PMID- 24284957
TI  - Evidence for brain activation in patients with takotsubo cardiomyopathy.
AB  - BACKGROUND: It remains to be elucidated whether brain activity is altered in
      takotsubo cardiomyopathy. METHODS AND RESULTS: We measured cerebral blood flow
      (CBF) in 3 consecutive patients with takotsubo cardiomyopathy using (99m)Tc ethyl
      cysteinate dimmer single photon-emission computed tomography (SPECT) in the acute
      and chronic phases. In all patients, CBF was significantly increased in the
      hippocampus, brainstem and basal ganglia and significantly decreased in the
      prefrontal cortex in the acute phase, which changes subsided in the chronic phase
      with full recovery of cardiac wall motion. CONCLUSIONS: These results provide the
      first direct evidence for brain activation in takotsubo cardiomyopathy.

PMID- 24284958
TI  - Pentraxin-3.

PMID- 24284959
TI  - Et4NI-catalyzed amidation of aldehydes and alcohols with ammonium salts.
AB  - An efficient method for the oxidative amidation of benzylic aldehydes or alcohols
      with ammonium salts has been developed for the synthesis of primary amides using
      Et4NI as the catalyst and tert-butyl hydroperoxide as the oxidant. This amidation
      reaction is operationally straightforward and provides primary amides in moderate
      to good yields under mild conditions. 

PMID- 24284960
TI  - Precision-cut liver slices from diet-induced obese rats exposed to ethanol are
      susceptible to oxidative stress and increased fatty acid synthesis.
AB  - Oxidative stress from fat accumulation in the liver has many deleterious effects.
      Many believe that there is a second hit that causes relatively benign fat
      accumulation to transform into liver failure. Therefore, we evaluated the effects
      of ethanol on ex vivo precision-cut liver slice cultures (PCLS) from rats fed a
      high-fat diet resulting in fatty liver. Age-matched male Sprague-Dawley rats were
      fed either high-fat (obese) (45% calories from fat, 4.73 kcal/g) or control diet
      for 13 mo. PCLS were prepared, incubated with 25 mM ethanol for 24, 48, and 72 h,
      harvested, and evaluated for ethanol metabolism, triglyceride production,
      oxidative stress, and cytokine expression. Ethanol metabolism and acetaldehyde
      production decreased in PCLS from obese rats compared with age-matched controls
      (AMC). Increased triglyceride and smooth muscle actin production was observed in
      PCLS from obese rats compared with AMC, which further increased following ethanol
      incubation. Lipid peroxidation, measured by thiobarbituric acid reactive
      substances assay, increased in response to ethanol, whereas GSH and heme
      oxygenase I levels were decreased. TNF-alpha and IL-6 levels were increased in
      the PCLS from obese rats and increased further with ethanol incubation. Diet
      induced fatty liver increases the susceptibility of the liver to toxins such as
      ethanol, possibly by the increased oxidative stress and cytokine production.
      These findings support the concept that the development of fatty liver sensitizes
      the liver to the effects of ethanol and leads to the start of liver failure,
      necrosis, and eventually cirrhosis. 

PMID- 24284961
TI  - Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF
      production via upregulation of COX-2 expression in esophageal cancer tissues.
AB  - Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA
      base excision repair and is also a multifunctional protein such as redox effector
      for several transcriptional factors. Our study was designed to investigate APE-1
      expression and to study its interaction with cyclooxygenase (COX)-2 expression
      and VEGF production in the esophageal cancer. The expression of APE-1, COX-2,
      monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF
      were evaluated by immunohistochemistry in 65 human esophageal squamous cell
      carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to
      detect mRNA and protein expression of APE-1 and p-signal transducer and activator
      of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE
      220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in
      the regulation of COX-2 expression, VEGF production, and antiapoptotic effect
      against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was
      observed in 92.3% (60/65) of all tissues. There was a significant relationship (P
      = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels
      in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1
      stimulation significantly increased mRNA and protein expression of APE-1.
      Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels
      in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1
      significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated
      esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased
      apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded
      that APE-1 is overexpressed and associated with COX-2 expression and VEGF
      production in esophageal cancer tissues. 

PMID- 24284962
TI  - Parenteral vs. oral iron: influence on hepcidin signaling pathways through
      analysis of Hfe/Tfr2-null mice.
AB  - Treatment for iron deficiency anemia can involve iron supplementation via dietary
      or parenteral routes that result in different cellular iron distributions. The
      effect of the administered iron on the iron regulatory system and hepcidin in the
      liver has not been well studied. Hepcidin, the liver-expressed central iron
      regulatory peptide, is itself regulated through the bone morphogenetic protein
      (BMP)/SMAD signaling pathway. Specifically, Bmp6 expression is upregulated in
      response to iron and induces hepcidin through phosphorylation of Smad1/5/8. The
      hemochromatosis-associated proteins Hfe and transferrin receptor 2 (Tfr2) are
      known upstream regulators of hepcidin, although their precise roles are still
      unclear. To investigate the mechanisms of this regulation and the roles of the
      Hfe and Tfr2, we subjected wild-type, Hfe(-/-), Tfr2(-/-), and Hfe(-/-)/Tfr2(-/-)
      mice to iron loading via dietary or parenteral routes. Systematic analysis
      demonstrated that Tfr2 is required for effective upregulation of Bmp6 in response
      to hepatocyte iron, but not nonparenchymal iron. Hfe is not required for Bmp6
      upregulation, regardless of iron localization, but rather, is required for
      efficient downstream transmission of the regulatory signal. Our results
      demonstrate that Hfe and Tfr2 play separate roles in the regulatory responses to
      iron compartmentalized in different cell types and further elucidates the
      regulatory mechanisms controlling iron homeostasis. 

PMID- 24284964
TI  - Intestine of dystrophic mice presents enhanced contractile resistance to
      stretching despite morphological impairment.
AB  - Protein dystrophin is a component of the dystrophin-associated protein complex,
      which links the contractile machinery to the plasma membrane and to the
      extracellular matrix. Its absence leads to a condition known as Duchenne muscular
      dystrophy (DMD), a disease characterized by progressive skeletal muscle
      degeneration, motor disability, and early death. In mdx mice, the most common DMD
      animal model, loss of muscle cells is observed, but the overall disease
      alterations are less intense than in DMD patients. Alterations in
      gastrointestinal tissues from DMD patients and mdx mice are not yet completely
      understood. Thus, we investigated the possible relationships between
      morphological (light and electron microscopy) and contractile function (by
      recording the isometric contractile response) with alterations in Ca2+ handling
      in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular
      layer thickness, a partial damage to the mucosal layer, and a partial damage to
      mitochondria of the intestinal myocytes. Functionally, the ileum from mdx
      presented an enhanced responsiveness during stretch, a mild impairment in both
      the electromechanical and pharmacomechanical signaling associated with altered
      calcium influx-induced contraction, with no alterations in the sarcoplasmic
      reticulum Ca2+ storage (maintenance of the caffeine and thapsigargin-induced
      contraction) compared with control animals. Thus, it is evidenced that the
      protein dystrophin plays an important role in the preservation of both the
      microstructure and ultrastructure of mice intestine, while exerting a minor but
      important role concerning the intestinal contractile responsiveness and calcium
      handling.

PMID- 24284963
TI  - Microbiota transplantation restores normal fecal bile acid composition in
      recurrent Clostridium difficile infection.
AB  - Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy
      for refractory, recurrent Clostridium difficile infection (CDI), which develops
      following antibiotic treatments. Intestinal microbiota play a critical role in
      the metabolism of bile acids in the colon, which in turn have major effects on
      the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid
      composition is altered in patients with recurrent CDI and that FMT results in its
      normalization. General metabolomics and targeted bile acid analyses were
      performed on fecal extracts from patients with recurrent CDI treated with FMT and
      their donors. In addition, 16S rRNA gene sequencing was used to determine the
      bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial
      composition of fecal samples from FMT recipients showed rapid change and became
      similar to the donor after the procedure. Pre-FMT fecal samples contained high
      concentrations of primary bile acids and bile salts, while secondary bile acids
      were nearly undetectable. In contrast, post-FMT fecal samples contained mostly
      secondary bile acids, as did non-CDI donor samples. Therefore, our analysis
      showed that FMT resulted in normalization of fecal bacterial community structure
      and metabolic composition. Importantly, metabolism of bile salts and primary bile
      acids to secondary bile acids is disrupted in patients with recurrent CDI, and
      FMT corrects this abnormality. Since individual bile salts and bile acids have
      pro-germinant and inhibitory activities, the changes suggest that correction of
      bile acid metabolism is likely a major mechanism by which FMT results in a cure
      and prevents recurrence of CDI. 

PMID- 24284966
TI  - Malignant melanoma arising at the site of a previously excised giant congenital
      melanocytic nevus.

PMID- 24284965
TI  - Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc
      receptors.
AB  - Dendritic cells (DCs) function as professional antigen presenting cells and are
      critical for linking innate immune responses to the induction of adaptive
      immunity. Many current cancer DC vaccine strategies rely on differentiating DCs,
      feeding them tumor antigens ex vivo, and infusing them into patients.
      Importantly, this strategy relies on prior knowledge of suitable "tumor-specific"
      antigens to prime an effective anti-tumor response. DCs express a variety of
      receptors specific for the Fc region of immunoglobulins, and antigen uptake via
      Fc receptors is highly efficient and facilitates antigen presentation to T cells.
      Therefore, we hypothesized that expression of the mouse IgG1 Fc region on the
      surface of tumors would enhance tumor cell uptake by DCs and other myeloid cells
      and promote the induction of anti-tumor T cell responses. To test this, we
      engineered a murine lymphoma cell line expressing surface IgG1 Fc and discovered
      that such tumor cells were taken up rapidly by DCs, leading to enhanced cross
      presentation of tumor-derived antigen to CD8+ T cells. IgG1-Fc tumors failed to
      grow in vivo and prophylactic vaccination of mice with IgG1-Fc tumors resulted in
      rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were
      able to slow the growth of an unmanipulated primary tumor when used as a
      therapeutic tumor vaccine. Our data demonstrate that engagement of Fc receptors
      by tumors expressing the Fc region of IgG1 is a viable strategy to induce
      efficient and protective anti-tumor CD8+ T cell responses without prior knowledge
      of tumor-specific antigens.

PMID- 24284967
TI  - Regional distribution of adult rheumatologists.
AB  - OBJECTIVE: To analyze the distribution of rheumatology practices in the US and
      factors associated with that distribution, in order to better understand the
      supply of the rheumatology workforce. METHODS: Using the American College of
      Rheumatology membership database, all practicing adult rheumatologist office
      addresses were mapped with ArcView software. The number of rheumatologists per
      Core Based Statistical Area (CBSA) was calculated. To investigate whether
      sociodemographic factors correlated with clustering of rheumatologists,
      covariates from the 2010 US Census for each CBSA, including age, sex,
      race/ethnicity, and median household income, were modeled. RESULTS: Many CBSAs,
      predominantly smaller micropolitan areas, did not have a practicing
      rheumatologist. For some of these smaller micropolitan areas (with populations of
      at least 40,000), the closest practicing rheumatologist was more than 200 miles
      away. However, we also identified several more-populous areas (populations of
      200,000 or more) without a practicing rheumatologist. Greater numbers of
      rheumatologists were more likely to practice in areas with higher population
      densities and higher median incomes. More rheumatologists were also found in
      CBSAs in which there were rheumatology training programs. CONCLUSION: These
      findings demonstrate that many smaller regions of the country have no or few
      practicing adult rheumatologists. Patients with chronic rheumatic conditions in
      these areas likely have limited access to rheumatology care. Policy changes could
      address potential regional rheumatology workforce shortages, but limitations of
      the current data would need to be addressed prior to implementation of such
      changes.

PMID- 24284969
TI  - Local models of fractional quantum Hall states in lattices and physical
      implementation.
AB  - The fractional quantum Hall effect is one of the most striking phenomena in
      condensed matter physics. It is described by a simple Laughlin wavefunction and
      has been thoroughly studied both theoretically and experimentally. In lattice
      systems, however, much less is currently known, and only few models and
      mechanisms leading to it have been identified. Here we propose a new way of
      constructing lattice Hamiltonians with local interactions and fractional quantum
      Hall like ground states. In particular, we obtain a spin 1/2 model with a bosonic
      Laughlin-like ground state, displaying a variety of topological features. We also
      demonstrate how such a model naturally emerges out of a Fermi-Hubbard-like model
      at half filling, in which the kinetic energy part possesses bands with non-zero
      Chern number, and we show how this model can be implemented in an optical lattice
      setup with present or planned technologies. 

PMID- 24284968
TI  - Voltage-gated and ATP-sensitive K+ channels are associated with cell
      proliferation and tumorigenesis of human glioma.
AB  - Increasing evidence indicates that potassium (K+) channels play important roles
      in the growth and development of human cancer. In the present study, we
      investigated the contribution of and the mechanism by which K+ channels control
      the proliferation and tumor development of U87-MG human glioma cells. A variety
      of K+ channel blockers and openers were used to differentiate the critical
      subtype of K+ channels involved. The in vitro data demonstrated that selective
      blockers of voltage-gated K+ (K(V)) channels or ATP-sensitive K+ (K(ATP))
      channels significantly inhibited the proliferation of U87-MG cells, blocked the
      cell cycle at the G0/G1 phase and induced apoptosis. In the U87-MG xenograft
      model in nude mice, K(V) or K(ATP) channel blockers markedly suppressed tumor
      growth in vivo. Furthermore, electrophysiological results showed that KV or KATP
      channel blockers inhibited K(V)/K(ATP) channel currents as well as cell
      proliferation and tumor growth over the same concentration range. In contrast,
      iberiotoxin, a selective blocker of calcium-activated K+ channels, had no
      apparent effect on the cell proliferation, cell cycle or apoptosis of U87-MG
      cells. In addition, the results of fluorescence assays indicated that blockers of
      K(V) or K(ATP) channels attenuated intracellular Ca2+ signaling by blocking Ca2+
      influx in U87-MG cells. Taken together, these data suggest that K(V) and K(ATP)
      channels play important roles in the proliferation of U87-MG cells and that the
      influence of K(V) and K(ATP) channels may be mediated by a Ca2+-dependent
      mechanism.

PMID- 24284971
TI  - Role of nasal packing in surgical outcome for chronic rhinosinusitis with
      polyposis.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the differences between biodegradable and
      nondegradable nasal dressings with regard to their effects on wound healing in
      the short and medium term and on surgical outcomes in the long term, after
      endoscopic sinus surgery (ESS). STUDY DESIGN: A prospective, randomized, partly
      blinded, controlled trial. METHODS: A total of 56 patients undergoing bilateral
      ESS for chronic rhinosinusitis with polyposis were enrolled and randomized to
      receive biodegradable (Nasopore; Stryker, Hamilton, ON, Canada) on one side and
      nondegradable packing (Merocel; Medtronic Xomed, Minneapolis, MN) on the opposite
      side. Postoperative morbidities (pain, bleeding, facial edema, nasal blockage)
      related to dressings were assessed on postoperative day 6. Wound healing (edema,
      crusting, secretions, synechia, granulation tissue formation, and percentage re
      epithelialization) were evaluated at 2 weeks, 1 month, 3 months, and 6 months
      using modified Lund-Kennedy scores. Long-term assessment at 12 months was done
      using validated Lund-Kennedy scores. RESULTS: Morbidities related to
      nondegradable packing were significantly higher than with degradable packing
      (Wilcoxon signed rank test, P<.01). Pain, bleeding, nasal blockage, and facial
      edema were significantly less with absorbable packing. No statistically
      significant difference was found between sinonasal cavities packed with
      biodegradable or nondegradable materials with regard to healing scores and
      percentage of re-epithelialization at 2 weeks, 1 month, 3 months, 6 months, and
      surgical outcomes at 1 year (P>.05). However, healing at 6 months was correlated
      with the preoperative Lund-Mackay radiology and surgery scores (Spearman's rho
      correlation test, P<.05 and P<.01, respectively). CONCLUSIONS: No significant
      healing or surgical outcome differences were found between biodegradable and
      nondegradable packing. However pain, bleeding, nasal blockage, and facial edema
      were lower with biodegradable packing. LEVEL OF EVIDENCE: 1b.

PMID- 24284972
TI  - Adenocarcinoma involving the tongue and the epiglottis in a horse.
AB  - Tumors involving the oral cavity of the horse are uncommon. No cases of equine
      adenocarcinoma on the dorsum of the tongue have been reported in the literature.
      We report a case of adenocarcinoma located on the dorsum of the posterior one
      third of the tongue in a 29-year-old gelding with severe dysphagia. Endoscopy
      revealed an epiglottis involvement, and histology was consistent with
      adenocarcinoma arising from minor salivary glands, which was associated with a
      severe fungal colonization of affected tissues. The goals of this report are to
      present an uncommon case of dorsum of the tongue-associated neoplasia and to
      highlight the association with atypical fungal colonization, to review the
      literature and to discuss possible clinical approach and prognosis. 

PMID- 24284974
TI  - Surveillance of avian paramyxovirus in migratory waterfowls in the San-in region
      of western Japan from 2006 to 2012.
AB  - Relatively little is known about the distribution of avian paramyxoviruses
      (APMVs) among wild birds in Japan. Surveillance of APMV in migratory waterfowl
      was conducted in the San-in region of western Japan during winters of 2006 to
      2012. A total of 16 avian paramyxoviruses consisting of 3 lentogenic Newcastle
      disease viruses (NDVs), 12 APMV-4 and 1 APMV-8 were isolated from 1,967 wild-bird
      fecal samples. The results show that NDV and APMV-4 are relatively widely
      distributed among wild waterfowl that migrate to Japan from northern regions.
      Phylogenetic analysis revealed that there was no genetic relationship between the
      isolates from wild birds and domestic poultry in Japan. However, surveillance of
      APMVs in wild waterfowl needs to be conducted due to the pathogenic potential of
      these isolates in domestic poultry.

PMID- 24284973
TI  - Seroepidemiology of reovirus in healthy dogs in six prefectures in Japan.
AB  - Reovirus infection is common in mammals. However, seroepidemiological data of
      reovirus neutralizing antibodies are limited in dogs. In this study, sera of 65
      healthy dogs from six prefectures across Japan were tested for neutralizing
      antibodies against reovirus serotype 1 strain Lang (T1L), serotype 2 strain Amy
      (T2A) and serotype 3 strain Dearing (T3D) using plaque reduction neutralization
      test (PRNT). Seropositivity against reovirus T1L, T2A and T3D was 53.85%, 33.85%
      and 46.15%, respectively. Distribution of reovirus seropositive samples displayed
      no distinguishable geographical pattern. However, reovirus seropositivity
      increased with age and in dogs housed outdoor. Co-infection of multiple reovirus
      serotypes in dogs was also detected. These data will provide valuable insights
      towards the usage of reovirus in oncolytic virotherapy in canine cancers.

PMID- 24284975
TI  - Effect of linseed oil and macadamia oil on metabolic changes induced by high-fat
      diet in mice.
AB  - The effects of linseed oil (LO) and macadamia oil (MO) on the metabolic changes
      induced by a high-fat diet (HFD) rich in saturated fatty acid were investigated.
      For the purpose of this study, the vegetable oil present in the HFD, i.e. soybean
      oil (SO) was replaced with LO (HFD-LO) or MO (HFD-MO). For comparative purposes,
      a group was included, which received a normal fat diet (NFD). Male Swiss mice (6
      week old) were used. After 14 days under the dietary conditions, the mice were
      fasted for 18 h, and experiments were then performed. The HFD-SO, HFD-LO and HFD
      MO groups showed higher glycaemia (p < 0.05 versus NFD). However, no significant
      effect was observed on glycaemia, liver gluconeogenesis and liver ketogenesis
      when SO was replaced by either LO or MO. The body weight and the sum of
      epididymal, mesenteric, retroperitoneal and inguinal fat weights were higher (p <
      0.05) in the HFD-SO and HFD-MO groups as compared with the NFD group. However,
      there was no significant difference in these parameters between the NFD and HFD
      LO groups. Thus, the protective role of LO on lipid accumulation induced by an
      HFD rich in saturated fatty acid is potentially mediated by the high content of
      omega-3 polyunsaturated fatty acid in LO.

PMID- 24284976
TI  - Prevention of thromboembolism in the patient with acute coronary syndrome and
      atrial fibrillation: the clinical dilemma of triple therapy.
AB  - PURPOSE OF REVIEW: Atrial fibrillation in patients with acute coronary syndrome
      (ACS) is associated with a high thromboembolic event rate. Combined oral
      anticoagulant (OAC) and antiplatelet therapy (APT) are often used to reduce
      thromboembolic risk, recurrent coronary ischemic events, and stent thrombosis,
      despite the high bleeding risk. This review is timely with the recent
      introduction of novel OACs (NOACs), more potent antiplatelet agents, and second
      generation coronary stents with a lower risk of late stent thrombosis, and
      considers strategies and new opportunities to reduce both thrombotic events and
      bleeding. RECENT FINDINGS: The benefits of NOACs in patients with atrial
      fibrillation have been shown in recent studies. New evidence indicates that
      single rather than dual APT may be adequate when an OAC is used in a patient with
      a recent coronary stent. Limited evidence suggests a NOAC is preferable to
      warfarin when additional APT is also required. SUMMARY: The implications of the
      new findings are to indicate strategies for more effective antithrombotic
      therapy, while minimizing the risk of major bleeding in patients with ACS and
      atrial fibrillation. However, additional research studies are required to further
      optimize treatment strategies in this high-risk population.

PMID- 24284977
TI  - Heritable thoracic aortic disorders.
AB  - PURPOSE OF REVIEW: Disease of the wall of the thoracic aorta has many causes:
      inflammation, infection and atherosclerosis are the most common 'acquired'
      causes, but even these have genetic predispositions. This article deals with
      aortic disease due to mutations in specific genes. The conditions can affect
      tissues and organs other than the aorta (syndromic) or be limited to the aorta
      (nonsyndromic). RECENT FINDINGS: A classification scheme based on the gene is
      emerging, those that affect primarily the extracellular matrix (e.g., FBN1,
      COL3A1), TGF-beta signaling (e.g., TGFBR1, TGFB2), or vascular smooth muscle cell
      contractility (e.g., ACTA2, MYH11). SUMMARY: Understanding pathogenesis is
      driving the development of novel therapies, such as angiotensin receptor
      blockade, which is in clinical trial. However, recurrent imaging, restriction of
      exercise, beta-adrenergic blockade, and prophylactic surgery remain effective in
      preventing dissection and sudden death.

PMID- 24284978
TI  - Implantable cardioverter-defibrillators in congenital heart disease.
AB  - PURPOSE OF REVIEW: Sudden cardiac death is a leading cause of mortality in
      patients with congenital heart disease (CHD), such that implantable cardioverter
      defibrillators (ICDs) are a critical component of care. Objectives of this review
      are to highlight recent advances regarding ICDs in CHD, with a focus on clinical
      indications, technical issues and solutions, and patient outcomes. RECENT
      FINDING: Evolving ICD indications in CHD are primarily derived from observational
      research or extrapolations from the general adult literature. Technical
      challenges to device implantation include obstructed vasculature or conduits,
      intracardiac shunts with their attendant risk for systemic thromboemboli, and
      lack of venous access to the heart. In selected patients, tailored epicardial
      systems may be considered that include subcutaneous, retrocardiac, and/or venous
      (e.g., azygous) coils. Alternatively, an entirely subcutaneous ICD may be a
      reasonable option in patients with no bradycardia or antitachycardia pacing
      indications. Long-term complications include inappropriate shocks, lead failure,
      reduction in quality of life, shock-related anxiety, and impaired sexual
      function. SUMMARY: Although ICDs undeniably save lives, challenges to applying
      this technology to patients with CHD include the paucity of evidence-based data
      to guide patient selection, technical challenges related to venous access,
      patient size, anatomic complexities, and a high rate of complications.

PMID- 24284979
TI  - Anthracycline-related cardiotoxicity in childhood cancer survivors.
AB  - PURPOSE OF REVIEW: Anthracyclines have markedly improved the survival rates of
      children with cancer. However, anthracycline-related cardiotoxicity is also well
      recognized and can compromise the long-term outcome in some patients. The
      challenge remains of how to balance the chemotherapeutic effects of anthracycline
      treatment with its potentially serious cardiovascular complications. Here, we
      review the pathophysiology, risk factors, clinical manifestations, prevention,
      and treatment of anthracycline-related cardiotoxicity. RECENT FINDINGS: Some risk
      factors and biomarkers associated with an increased probability of anthracycline
      related cardiotoxicity have been identified. Modifying the structural forms and
      dosages of anthracyclines and coadministering cardioprotective agents may prevent
      some of these cardiotoxic effects. Cardiovascular complications have also been
      treated with angiotensin-converting enzyme inhibitors, beta-blockers, and growth
      hormone replacement therapy. Cardiac transplantation remains the treatment of
      last resort. SUMMARY: Despite major advances in cancer treatment, anthracycline
      related cardiotoxicity remains a major cause of morbidity and mortality in
      survivors of childhood cancer. Promising areas of research include: use of
      biomarkers for early recognition of cardiac injury in children receiving
      chemotherapy, development and application of cardioprotective agents for
      prevention of cardiotoxicity, and advancements in therapies for cardiac
      dysfunction in children after anthracycline treatment.

PMID- 24284980
TI  - Advanced left-ventricular lead placement techniques for cardiac resynchronization
      therapy.
AB  - PURPOSE OF REVIEW: Due to complex venous anatomy and limitations in lead delivery
      tools and technology, the incidence of failed left-ventricular lead implants
      continues to be as high as 10%. RECENT FINDINGS: A move towards an interventional
      approach to left-ventricular lead implantation has provided viable alternatives
      to surgical lead implantation. The use of telescoping sheaths, gooseneck snares
      and percutaneous balloon venoplasty may reduce procedural times by facilitating
      lead delivery despite challenging venous anatomy. In addition, recent
      advancements in left-ventricular lead technology now allow implanting physicians
      to overcome commonly encountered obstacles such as high thresholds and phrenic
      nerve stimulation, without having to move the lead from a stable position. For
      those with suboptimal or inaccessible coronary vein targets, a simplified
      transseptal endocardial implant approach has also been described. SUMMARY: These
      recent advances in implant techniques and left-ventricular lead technology
      provide promising solutions to commonly encountered procedural obstacles in the
      implementation of resynchronization therapy. These alternative strategies will
      hopefully reduce the rate of failed implants and referrals for surgical
      epicardial leads.

PMID- 24284981
TI  - Secondary prevention of sudden cardiac death: does it work in children?
AB  - PURPOSE OF REVIEW: Over half of young sudden cardiac arrest victims show no prior
      warning signs or symptoms and survival depends on secondary prevention, notably
      prompt initiation of cardiopulmonary resuscitation (CPR) and the use of an
      automated external defibrillator (AED), for out-of-hospital arrests. There is
      increasing public interest in and uptake of public access defibrillation programs
      in communities and schools. Our purpose was to review recent data on sudden
      cardiac arrest in children and its outcome to identify ways to improve the
      current low survival rate of youth who experience sudden cardiac arrest. RECENT
      FINDINGS: Increases in bystander cardiopulmonary resuscitation in Norway to 73%
      have occurred alongside increasing survival from sudden cardiac arrest from
      shockable rhythms to 52%. Studies in Denmark and the US show that survival of 69
      74% is possible when a shockable rhythm is present and an automated external
      defibrillator is immediately applied. Up to 70-80% of US schools have automated
      external defibrillators, but not all have effective emergency action plans to
      maximize the impact of the presence of the AED. SUMMARY: Studies suggest that
      education to increase bystander CPR and implementation of school AEDs and other
      public access defibrillation programs improve the survival of youth experiencing
      sudden cardiac arrest to 74% when optimal programs are in place. Methods to
      enhance such programs are presented. All involved with the health and education
      of youth are urged to implement best practices to protect youth and improve
      survival from sudden cardiac arrest.

PMID- 24284982
TI  - The subcutaneous implantable cardioverter-defibrillator.
AB  - PURPOSE OF REVIEW: To consider the case of need that underpinned the development
      of the subcutaneous implantable cardioverter-defibrillator (SICD), the
      preclinical and clinical data obtained so far, its current role and likely
      future. RECENT FINDINGS: The data from prospective clinical evaluation of the
      device demonstrated safety and efficacy leading to Food and Drug Administration
      approval. This superseded earlier reports from Europe that raised some clinical
      concerns, previously anticipated through the introduction of new technology.
      Recent estimates indicate maybe 55% of patients in routine clinical practice
      needing an ICD are potentially suitable for a subcutaneous device. SUMMARY: The
      SICD provides a useful alternative for high-energy (ICD) therapy in those deemed
      at risk and who need defibrillation and in whom there are no indications for
      cardiac resynchronization, bradycardia support or antitachycardia pacing. There
      is the possibility of both higher specificity and the avoidance of myo-cellular
      damage with shock delivery, and if these two aspects play out subcutaneous
      defibrillation could become an option of choice in many settings.

PMID- 24284983
TI  - Alumina/polymer-coated nanocrystals with extremely high stability used as a color
      conversion material in LEDs.
AB  - The long-term stability of quantum dot (QD)-based devices under harsh
      environmental conditions has been a critical bottleneck to be resolved for
      commercial use. Here, we demonstrate an extremely stable QD/alumina/polymer
      hybrid structure by combining internal atomic layer deposition (ALD) infilling
      with polymer encapsulation. ALD infilling and polymer encapsulation of QDs
      synergistically prohibit the degradation of QDs in terms of optical, thermal and
      humid attacks. Our hybrid QD/alumina/polymer film structure showed no noticeable
      reduction in photoluminescence even in a commercial grade test (85% humidity at
      85 degrees C) over 28 days. In addition, we successfully fabricated a QD-based
      light-emitting device with excellent long-term stability by incorporating hybrid
      QD/alumina/polymer film as a color conversion material on light-emitting diode
      chips.

PMID- 24284984
TI  - Plasma long-chain free fatty acids predict mammalian longevity.
AB  - Membrane lipid composition is an important correlate of the rate of aging of
      animals and, therefore, the determination of their longevity. In the present
      work, the use of high-throughput technologies allowed us to determine the plasma
      lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5
      to 120 years. The non-targeted approach revealed a specie-specific lipidomic
      profile that accurately predicts the animal longevity. The regression analysis
      between lipid species and longevity demonstrated that the longer the longevity of
      a species, the lower is its plasma long-chain free fatty acid (LC-FFA)
      concentrations, peroxidizability index, and lipid peroxidation-derived products
      content. The inverse association between longevity and LC-FFA persisted after
      correction for body mass and phylogenetic interdependence. These results indicate
      that the lipidomic signature is an optimized feature associated with animal
      longevity, emerging LC-FFA as a potential biomarker of longevity. 

PMID- 24284985
TI  - Three randomised phase I/IIa trials of 5% cis-urocanic acid emulsion cream in
      healthy adult subjects and in patients with atopic dermatitis.
AB  - New treatment modalities are needed in atopic dermatitis. We evaluated the
      pharmacokinetics, safety, tolerability, and efficacy of topical cis-urocanic acid
      (cis-UCA) cream in randomised vehicle-controlled double-blinded clinical trials.
      The subjects received 5% cis-UCA emulsion cream and control vehicle on volar
      forearms after right-left randomisation. Study 1: 16 healthy subjects received
      one dose on the skin and, a week later, on DMSO-irritated skin. Study 2: 16
      healthy subjects received 2 daily doses for 10 days. Study 3: 13 patients with
      mild to moderate disease were treated on selected skin lesions twice daily for 28
      days. Study treatments were well tolerated. cis-UCA remained close to endogenous
      levels in plasma and urine. cis-UCA reduced transepidermal water loss (TEWL) both
      in healthy subjects and in the patients. Eczema area severity index and
      physician's global assessment improved from baseline with both treatments. cis
      UCA cream improved skin barrier function and suppressed inflammation in the human
      skin.

PMID- 24284986
TI  - Model-based estimation of optimal temperature profile during simultaneous
      saccharification and fermentation of Arundo donax.
AB  - A kinetic model fitted to enzymatic hydrolysis of Arundo donax was coupled to a
      fermentation kinetic model derived from simultaneous saccharification and
      fermentation (SSF) experiments at different temperatures for the determination of
      optimal temperature profile (between 36 and 45 degrees C) using iterative dynamic
      programming (IDP). A sensitivity analysis of enzyme kinetic model not only
      facilitated model reduction in terms of number of parameters, but also enabled
      artifacts from parameter estimations to be identified. In separate fermentation
      experiments conducted at 35, 40, 45, and 50 degrees C using ~40 g/L background
      glucose in fiber-free liquid fraction of Arundo it was found that growth was
      possible at 40 degrees C, but the fermentation capacity was completely lost after
      12 h at 50 degrees C. The final ethanol concentration obtained after 120 h in
      isothermal SSF experiments at 36, 39, 42, and 45 degrees C were 10.6, 13.7, 14.2,
      and 12.5 g/L, respectively. The predicted optimal temperature profile in SSF
      determined by iterative dynamic programming was (i) gradual decrease from 40 to
      37.5 degrees C until 16 h, (ii) a linear increase upto 45 degrees C until 80 h,
      and (iii) gradual decrease by 1 degrees C until 120 h. Experimental results were
      in good agreement with the model predictions. The ethanol concentration after 72
      h obtained in the optimal case was 13.6 g/L in comparison to 9.1, 12.2, 12.6, and
      11.6 g/L for ISO-SSF at 36, 39, 42, and 45 degrees C, respectively. Moreover this
      value was 95.8% of the final value achieved at the end of 120 h, indicating that
      the process times could be significantly shortened by using non-isothermal SSF.

PMID- 24284987
TI  - Estimation of the origin of ventricular outflow tract arrhythmia using
      synthesized right-sided chest leads.
AB  - AIMS: For successful ablation of ventricular outflow tract arrhythmia, estimation
      of its origin prior to the procedure can be useful. Morphology and lead placement
      in the right thoracic area may be useful for this purpose. Electrocardiography
      using synthesized right-sided chest leads (Syn-V3R, Syn-V4R, and Syn-V5R) is
      performed using standard leads without any additional leads. This study evaluated
      the usefulness of synthesized right-sided chest leads in estimating the origin of
      ventricular outflow tract arrhythmia. METHODS AND RESULTS: This retrospective
      study included 63 patients in whom successful ablation of ventricular outflow
      tract arrhythmia was performed. Numbers of arrhythmias originating from the left
      ventricle, the septum of the right ventricle, and the free wall of the right
      ventricle were 11, 40, and 13, respectively. In one patient, two different left
      ventricular outflow tract origins were found. Electrocardiographic recordings
      from right-sided chest leads were divided into three types as follows: those in
      which an R > S concordance, a transitional zone, or an R < S concordance were
      detected. In all left arrhythmia cases, R > S concordance was observed. A
      transitional zone was evident in 34 of 40 cases of right ventricular outflow
      tract arrhythmia originating in the ventricular septum, and an R < S concordance
      was observed in 6 of the 40 cases. However, an R < S concordance was found in all
      cases of right ventricular outflow tract arrhythmia originating in the free wall.
      CONCLUSION: Synthesized right-sided chest lead electrocardiography may be useful
      for estimating the origin of ventricular outflow tract arrhythmia.

PMID- 24284988
TI  - Acetylsalicylic acid for stroke prevention in atrial fibrillation: a conspiracy
      that needs to end?

PMID- 24284989
TI  - Entrapment and fracture of a 'lasso-like' ACHIEVETM catheter in a pulmonary vein
      branch during isolation by balloon cryoablation.

PMID- 24284990
TI  - Evaluation of the (14)C-urea breath test using indigenously produced (14)C-urea
      capsules and a modified technique for trapping exhaled breath: a pilot study.
AB  - The carbon urea breath test ((14)C-UBT) is a noninvasive technique used to detect
      Helicobacter pylori infection in patients presenting with dyspeptic symptoms. The
      present study was undertaken to determine the efficacy of indigenously produced
      (14)C-UBT capsules by the Board of Radiation and Isotope Technology, India.
      Thirty consecutive patients with dyspeptic symptoms were included in the study.
      After ingestion of capsules, breath samples were collected in a CO2-trapping
      solution to which a scintillation cocktail was added. After 24 h, the whole
      sample was counted in a liquid scintillation counter along with a standard of
      (14)C. The number of disintegrations of (14)C per minute in the breath sample was
      calculated. The results were compared with histopathological reports. Of 30
      patients, 19 were positive and 11 were negative on (14)C-UBT. Histopathological
      reports confirmed 27 cases as positive and three as negative for H. pylori. Thus,
      the results of (14)C-UBT were concordant with histopathological results in 22/30
      (73.3%) cases. Considering histopathology as the gold standard, the sensitivity,
      specificity, and positive predictive value of (14)C-UBT using indigenously
      produced capsules were found to be 70.33, 100, and 100%, respectively. On
      critical analysis of the discordant results, we observed that six patients had
      undergone H. pylori eradication therapy exactly 4 weeks before the test. When
      these six patients were excluded from the analysis, the sensitivity, specificity,
      and positive predictive value were found to be 90.05, 100, and 100%,
      respectively, which compared well with the values obtained using the standard
      procedure. The study demonstrates adequate efficacy of the indigenous methodology
      in newly diagnosed symptomatic patients with acid peptic disorders. The analyses
      of the results indicate that the test should be preferably employed after the
      recommended period of 1 month following completion of eradication therapy.

PMID- 24284991
TI  - Known players, new interplay in atherogenesis: Chronic shear stress and
      carbamylated-LDL induce and modulate expression of atherogenic LR11 in human
      coronary artery endothelium.
AB  - In this study we examined whether low-density lipoprotein (LDL) receptor family
      members represent a link between blood flow characteristics and modified low
      density lipoproteins involved in endothelial injury, a pivotal factor in
      atherogenesis. We demonstrated the expression of pro-atherogenic LDL receptor
      relative (LR11) for the first time in human coronary artery endothelial cells
      (HCAEC) in vitro and in vivo. Next, LR11 expression and regulation were explored
      in HCAEC cultured conventionally or on the inner surface of hollow fiber
      capillaries under exposure to shear stress for 10 days in the presence or absence
      of LDL. There was no LR11 expression under static conditions. When exposed to
      chronic low shear stress (2.5 dynes/cm2) transmembrane and soluble endothelial
      LR11 were detected in high levels irrespective of the type of LDL added
      (carbamylated or native). In contrast, chronic high shear stress (25 dynes/cm2)
      inhibited the LR11-inducing effect of LDL such that transmembrane and soluble
      LR11 expression became non-detectable with native LDL. Carbamylated LDL
      significantly counteracted this atheroprotective effect of high shear stress as
      shown by lower, yet sustained expression of soluble and transmembrane LR11.
      Oxidised LDL showed similar effects compared to carbamylated LDL but caused
      significantly lower LR11 expression under chronic high shear stress. Medium from
      HCAEC under LR11-inducing conditions enhanced vascular smooth muscle cell
      migration, which was abrogated by the anti-LR11 antibody. Expression of LR11
      depended entirely on p38MAPK phosphorylation. We conclude that coronary
      endothelial LR11 expression modulated by LDL and chronic shear stress contributes
      to atherogenesis. LR11 and p38MAPK are potential targets for prevention of
      atherosclerosis.

PMID- 24284992
TI  - Use of graft flow measurement and computerized tomography angiography to evaluate
      patency of endoscopically harvested radial artery as sequential graft in coronary
      artery bypass surgery.
AB  - AIM: Endoscopic radial artery (RA) graft harvesting in coronary artery bypass
      surgery (CABG) is attractive but concern remains regarding early graft failure.
      We evaluated RA graft patency via intraoperative graft flow measurements and mid
      term computerized tomography angiography (CTA). METHODS: The patients who had RA
      harvested by endoscopic technique which was used as sequential grafts were
      retrospectively reviewed. Graft quality was confirmed by intraoperative transit
      time flow measurements. Graft stenosis was defined as stenosis >70% on CTA, 6-12
      months postoperatively. RESULTS: From 2007 to 2011, 58 patients underwent
      endoscopic RA harvesting for sequential bypassed grafts. All received total
      arterialized grafts, including 22 (38%) bilateral internal thoracic arteries
      (ITAs), with 208 total bypassed grafts (mean: 3.59+/-0.52) and 128 RA bypassed
      grafts (mean: 2.21+/-0.35). Off-pump technique was performed in 43 (84%) of 51
      isolated CABG patients. The pulsatility index of graft flow of the left, right
      ITA and sequential RA grafts with 2 or 3 targets were 1.8+/-0.7, 2+/-0.8, 1.9+/
      0.4, and 1.7+/-0.7, respectively. There was no hospital mortality, and median
      intensive care unit and hospital stay was 2 and 8 days. Follow-up was completed
      in 57 patients, but 3 patients refused CTA due to lack of exertional angina.
      Stenosis of the left, right ITA, and RA grafts occurred in 1/54 (1.9%), 1/21
      (4.8%), and 11/120 (9.2%). After a mean of 35.8+/-10.9 (median: 30.7) months
      follow-up, there was no late mortality and one documented myocardial infarction
      was reported. Age, diabetes, previous percutaneous coronary intervention, off
      pump technique, RA target number, and graft flow or pulsatility index did not
      predict RA stenosis. Only RA grafts targeting the circumflex territory had an
      adverse impact. CONCLUSION: The RA of appropriately selected patients can be
      harvested safely by endoscopic technique and can be used as sequential grafts for
      CABG with satisfactory outcomes. Intraoperative flow measurement can assure the
      quality of the grafts. CTA is a valuable tool for patency follow-up.

PMID- 24284993
TI  - The certainty of death and the uncertainty of treatments.

PMID- 24284994
TI  - Junk food and heart disease: the missing tooth.

PMID- 24284995
TI  - Idealism includes compassion and commitment to patients.

PMID- 24284996
TI  - UK Medical Research Council and multicentre clinical trials: from a damning
      report to international recognition.

PMID- 24285000
TI  - The regional distribution of rheumatologists: what can we do, what should we do?

PMID- 24285001
TI  - Flaky paint dermatosis. Kwashiorkor.

PMID- 24285002
TI  - The changing epidemiology of Clostridium difficile infection.
AB  - PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a growing concern and
      has a substantial impact on morbidity and mortality. Epidemiology of CDI has
      dramatically changed over the last decade. Diagnostic and treatment strategies
      are even more complicated given the wide variety of available diagnostic methods
      and the emergence of refractory or recurrent CDI. This review is intended to
      provide information on current CDI epidemiology and guidance for evidence-based
      diagnosis and management strategies. RECENT FINDINGS: Various studies from the
      United States, Europe, and Canada revealed increased incidence of CDI since 2000.
      Although CDI has long been associated with healthcare settings, recent studies
      indicate it is more common in the community than previously recognized. For
      diagnostic strategies, newer testing methods, including nucleic acid
      amplification tests, have enhanced sensitivity compared with toxin testing, but
      at the expense of decreased specificity. New agents for treating CDI are being
      developed and higher quality data to support fecal microbiota transplantation for
      treating recurrent CDI are emerging. SUMMARY: CDI epidemiology continues to
      evolve. Prompt recognition and an evidence-based treatment approach is the key to
      successfully manage CDI. Further, studies on diagnostic and therapeutic
      strategies are needed to further improve patient outcomes.

PMID- 24285003
TI  - Treatment of ulcerative colitis.
AB  - PURPOSE OF REVIEW: Ulcerative colitis is a chronic inflammatory disease of the
      colon of unknown cause that is characterized by alternating intervals of active
      and inactive disease in 80-90% of patients. The primary goal of treatment is to
      induce and maintain remission using therapy tailored to the individual patient.
      The purpose of this review was to describe the management of ulcerative colitis
      with emphasis on the use of anti-tumor necrosis factor (TNF) agents. RECENT
      FINDINGS: Recent research has shown that new anti-TNF agents, adalimumab (ADA)
      and golimumab, are effective in induction of remission and maintenance of
      remission in patients with extensive ulcerative colitis. In a recent study,
      infliximab was found to have comparable efficacy to cyclosporine in treatment of
      acute severe refractory to corticosteroids ulcerative colitis. SUMMARY: Anti-TNF
      therapy should be initiated in patients with acute severe refractory to
      corticosteroids ulcerative colitis and in patients with moderate-to-severe
      ulcerative colitis who are not responsive to conventional treatment with
      aminosalicylates, corticosteroids and immune modulators. Alternatives to
      infliximab are ADA and golimumab. Future research is needed to further assess the
      long-term efficacy and safety of ADA and golimumab in ulcerative colitis.

PMID- 24285004
TI  - Electronic structure predictions of the properties of non-innocent P-ligands in
      group 6B transition metal complexes.
AB  - Neutral group 6B (Cr, Mo, W) pentacarbonyl complexes M(CO)5-L possessing various
      P-ligands such as phosphines, phosphaalkenes, and phospha-quinomethanes can form
      radical cations and anions under redox conditions. There is significant interest
      in whether the radical site is localized on the metal or on a "non-innocent"
      ligand. Density functional theory was used to predict whether the radicals of the
      complexes behave as metal or ligand-centered radicals and whether these compounds
      could form in solution or as an ion pair with various oxidizing and reducing
      agents. The quinone-like ligands are predicted to be ligand centered radicals
      when they are anions and metal centered radicals when they are cations. The
      predicted reaction energies for single electron transfer (SET) reactions
      involving the quinone like ligands are negative or near thermoneutral for both
      radicals in polar solutions and as solid state ion pairs. The energetics of the
      SET reactions can be controlled by the nature of L, the nature of the
      oxidizing/reducing agent, and the solvent polarity. Such complexes could be used
      as flexible catalysts for single electron transfer reactions. 

PMID- 24285005
TI  - Oxidative stress as a cost of reproduction: beyond the simplistic trade-off
      model.
AB  - The idea that oxidative stress may underpin life history trade-offs has become
      extremely popular. However, experimental support for the concept has proved
      equivocal. It has recently been suggested that this might be because of flaws in
      the design of existing studies. Here, we explore the background to the oxidative
      stress hypothesis and highlight some of the complexities in testing it. We
      conclude that the approach recently suggested to be least useful in this context
      (comparing reproducing to non-reproducing animals) may in fact be the most
      powerful. Moreover, suggested alternative approaches of limiting food supply or
      manipulating litter sizes have many complexities and problems. We suggest some
      useful alternative approaches that have not been previously advocated,
      particularly the study of individuals reproducing at greater parity later in
      life. Finally, the measures of oxidative stress and tissues that are analysed
      influence the experimental outcome. This suggests our conceptual model of the
      trade-off is currently too simplistic, and that studies based on single or
      limited numbers of assays, or restricted to single tissues, whether they support
      or refute the theory, should be interpreted with great caution. 

PMID- 24285006
TI  - Solution-processed small-molecule solar cells: breaking the 10% power conversion
      efficiency.
AB  - A two-dimensional conjugated small molecule (SMPV1) was designed and synthesized
      for high performance solution-processed organic solar cells. This study explores
      the photovoltaic properties of this molecule as a donor, with a fullerene
      derivative as an acceptor, using solution processing in single junction and
      double junction tandem solar cells. The single junction solar cells based on
      SMPV1 exhibited a certified power conversion efficiency of 8.02% under AM 1.5 G
      irradiation (100 mW cm(-2)). A homo-tandem solar cell based on SMPV1 was
      constructed with a novel interlayer (or tunnel junction) consisting of bilayer
      conjugated polyelectrolyte, demonstrating an unprecedented PCE of 10.1%. These
      results strongly suggest solution-processed small molecular materials are
      excellent candidates for organic solar cells.

PMID- 24285007
TI  - Insights into graphene functionalization by single atom doping.
AB  - Chemical modification of graphene is a common approach to control its electronic
      properties and hence fabricate electronic devices with new or improved
      functionalities. In this work we analyze, with density functional based
      calculations, the effect of chemical adsorption of fluorine atoms at different
      coverage levels on the electronic structure of graphene. We suggest a simple and
      general model for the shift of the Fermi level with coverage level and show the
      trends of the band gap and the Fermi level shift with coverage. We then show that
      the same model can be applied to explain the Fermi level shift in a different
      system of nitrogen substitution in graphene. Finally, we analyze the resulting
      charge transfer patterns and show that they are consistent with the model for the
      Fermi level shift. 

PMID- 24285008
TI  - Tobacco exposure increased airway limitation in dogs with chronic cough.

PMID- 24285009
TI  - Thyroxine concentrations in ruminant health monitoring and diagnostic blood
      samples.

PMID- 24285010
TI  - Identification of a porcine pestivirus as a border disease virus from naturally
      infected pigs in Spain.

PMID- 24285012
TI  - Epigenetic diversity increases the productivity and stability of plant
      populations.
AB  - Biological diversity within species can be an important driver of population and
      ecosystem functioning. Until now, such within-species diversity effects have been
      attributed to underlying variation in DNA sequence. However, within-species
      differences, and thus potentially functional biodiversity, can also be created by
      epigenetic variation. Here, we show that epigenetic diversity increases the
      productivity and stability of plant populations. Epigenetically diverse
      populations of Arabidopsis thaliana produce up to 40% more biomass than
      epigenetically uniform populations. The positive epigenetic diversity effects are
      strongest when populations are grown together with competitors and infected with
      pathogens, and they seem to be partly driven by complementarity among
      epigenotypes. Our study has two implications: first, we may need to re-evaluate
      previous within-species diversity studies where some effects could reflect
      epigenetic diversity; second, we need to incorporate epigenetics into basic
      ecological research, by quantifying natural epigenetic diversity and testing for
      its ecological consequences across many different species. 

PMID- 24285011
TI  - A new high-speed droplet-real-time polymerase chain reaction method can detect
      bovine respiratory syncytial virus in less than 10 min.
AB  - The polymerase chain reaction (PCR) has been widely used for diagnosis of
      infectious diseases of domestic animals. Rapid detection of respiratory pathogens
      of cattle is useful for making therapeutic decisions. Therefore, we developed a
      new genetic-based method called droplet-real-time PCR, which can detect bovine
      respiratory syncytial virus (BRSV) within 10 min. Our droplet-real-time PCR
      markedly reduced the reaction time of reverse transcription-PCR while maintaining
      the same sensitivity as conventional real-time PCR, and it can be used as a rapid
      assay for detection of BRSV. Furthermore, our method is potentially applicable
      for rapid diagnosis of almost all infectious diseases, including highly
      pathogenic avian influenza virus. 

PMID- 24285013
TI  - Medical literature, vena cava filters and evidence of efficacy. A descriptive
      review.
AB  - Up to 15% of all patients with venous thromboembolism (VTE) receive an inferior
      vena cava filter, and prophylactic placements are increasing. To determine
      whether current use of filters is based on robust evidence, a global review of
      the recent (2001-2012) literature on filters was undertaken. The MEDLINE database
      was searched for articles related to filters appearing during the period 2001
      2012, updating a prior search of literature from 1975-2001. All retrieved
      articles were analysed, classified into predetermined categories and compared to
      the prior analysis; randomised and large (>100 patients with a filter)
      comparative non-randomised clinical studies were read in full. The 651 articles,
      vs 568 in the period 1975-2000, consisted mainly of retrospective series (37.8%),
      case reports (31.7%), reviews (14.7%, vs 6.7%, p<0.001), animal and/or in vitro
      studies (7.5%, vs 12.9%, p=0.002), and prospective series or trials (4.9%, vs
      7.4%, p=0.07). Of 4 new randomised trials (RCT), none were designed to test the
      efficacy of the device; to date, only one RCT has attempted to ascertain
      efficacy, occurring during the period 1975-2000. Eleven large non-randomised
      studies compared clinical outcomes of patients with and without filters, in VTE
      patients (n=5) or prophylactic indications (n=6); two studies found statistically
      significant relationships between filter use and lower mortality rates, though
      none could demonstrate a causal relationship. Hence, the plethoric literature on
      filters parallels growing experience with these devices, but still fails to
      provide reliable evidence that filter use improves relevant clinical outcomes. No
      indication for filter placement is based on appropriate scientific evidence. 

PMID- 24285015
TI  - Final results of phase II trial of doxorubicin HCl liposome injection followed by
      bexarotene in advanced cutaneous T-cell lymphoma.
AB  - BACKGROUND: High response rates for doxorubicin HCl liposome injection (DLI) in
      cutaneous T-cell lymphoma (CTCL) have been reported with vague criteria until
      recently. Approximately 50% of CTCL patients respond to bexarotene (Bex).
      PATIENTS AND METHODS: A phase II trial was carried out to clarify the true
      overall response rate (ORR) for DLI and to assess the role of sequential Bex.
      Patients were treated with DLI 20 mg/m(2) i.v. every 2 weeks for 16 weeks (8
      doses) followed by 16 weeks with Bex 300 mg/m(2) orally. Response assessments
      were carried out after 16 (DLI) and 32 weeks (Bex). Skin responses were measured
      by the modified Severity-Weighted Assessment Tool (mSWAT) and the Composite
      Assessment of Index Lesion Severity (CA). RESULTS: Thirty-seven patients were
      treated: stage IV (22, 8 with Sezary syndrome), IIB (10), earlier stage
      refractory to skin-directed therapies or radiation therapy (5). For 34 assessable
      patients: ORR 14/34 [41%: partial response (PR) 12, clinical complete response
      (CCR) 2]. Maximum responses were all seen after 16 weeks DLI. Median progression
      free survival (PFS) was 5 months. There were 22 deaths: 21 of disease and 1 of
      heart failure. Twenty-seven grade 3 and 5 grade 4 toxic events were observed.
      CONCLUSION(S): With strict criteria, DLI ORR is among the highest reported for
      single agents in CTCL. Sequential Bex did not increase the response rate or
      duration.

PMID- 24285016
TI  - ATM down-regulation is associated with poor prognosis in sporadic breast
      carcinomas.
AB  - BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been
      reported in sporadic breast carcinomas (BC); however, the prognostic value and
      mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and
      miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p and miR-18a)
      expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC
      and 3 normal breast samples. ATM protein expression was assessed by
      immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy
      number alteration was detected by array comparative genomic hybridization (aCGH)
      in 42 tumours. RESULTS: Low ATM levels were associated with tumour grade. Absence
      of ATM protein expression was associated with distant metastasis (P < 0.001),
      reduced disease-free survival (DFS, P < 0.001) and cancer-specific survival (CSS,
      P < 0.001). Multivariate analysis indicated ATM protein expression as an
      independent prognostic marker for DFS (P = 0.001, HR = 0.579) and CSS (P = 0.001,
      HR = 0.554). ATM copy number loss was detected in 12% of tumours and associated
      with lower mRNA levels. miR-421 over-expression was detected in 36.5% of cases
      which exhibit lower ATM transcript levels (P = 0.075, r = -0.249). CONCLUSIONS:
      The data suggest that ATM protein expression is an independent prognostic marker
      in sporadic BC. Gene copy number loss and miR-421 over-expression may be involved
      in ATM deregulation in BC.

PMID- 24285017
TI  - Antibody-based immunotherapy for ovarian cancer: where are we at?
AB  - Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian
      cancer treatment. However, as mortality from advanced ovarian cancer remains very
      high, novel therapies are required to be integrated into existing treatment
      regimens. Immunotherapy represents an alternative and rational therapeutic
      approach for ovarian cancer based on a body of evidence supporting a protective
      role of the immune system against these cancers, and on the clinical success of
      immunotherapy in other malignancies. Whether or not immunotherapy will have a
      role in the future management of ovarian cancer is too early to tell, but
      research in this field is active. This review will discuss recent clinical
      developments of selected immunotherapies for ovarian cancer which fulfil the
      following criteria: (i) they are antibody-based, (ii) target a distinct
      immunological pathway, and (iii) have reached the clinical trial stage.
      Specifically, the focus is on Catumaxomab (anti-EpCAM*anti-CD3), Abagovomab,
      Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and
      MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and
      exhibits promise with reports, showing that it can cause a significant and
      sustained reduction in ascites. Phase I-III clinical trials continue to be
      conducted on the other antibodies, some of which have had encouraging reports. We
      will also provide our perspective on the future of immunotherapy for ovarian
      cancer, and how it may be best employed in treatment regimens.

PMID- 24285018
TI  - Adherence to consensus-based diagnosis and treatment guidelines in adult soft
      tissue sarcoma patients: a French prospective population-based study.
AB  - BACKGROUND: Soft-tissue sarcomas (STSs) are rare tumors with varied histological
      presentations. Management and treatment are thus complex, but crucial for patient
      outcomes. We assess adherence to adult STS management guidelines across two
      French regions (10% of the French population). We also report standardized
      incidence. PATIENTS AND METHODS: STS patients diagnosed from 1 November 2006 to
      31 December 2007 were identified from pathology reports, medical hospital
      records, and cancer registries. Guideline adherence was assessed by 23 criteria
      (validated by Delphi consensus method), and age and sex-standardized incidence
      rates estimated. Associations between patient, treatment, and institutional
      factors and adherence with three major composite criteria relating to diagnostic
      imaging and biopsy as well as multidisciplinary team (MDT) case-review are
      reported. RESULTS: Two hundred and seventy-four patients were included (57.7%
      male, mean age 60.8 years). Practices were relatively compliant overall, with
      over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus
      had low adherence: receiving histological diagnosis before surgery, adequacy of
      histological diagnosis (adherence around 50% for both), and MDT discussion before
      surgery (adherence <30%). Treatment outside of specialized centers was associated
      with lower adherence for all three composite criteria, and specific tumor sites
      and/or features were associated with lower adherence for diagnostic imaging,
      methods, and MDT meetings. STS standardized incidence rates were 4.09 (European
      population) and 3.33 (World) /100 000 inhabitants. CONCLUSIONS: Initial STS
      diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings)
      need improving, particularly outside specialized centers. Educational
      interventions to increase surgeon's sarcoma awareness and knowledge and to raise
      patients' awareness of the importance of seeking expert care are necessary.

PMID- 24285019
TI  - Aprepitant does not alter prednisolone pharmacokinetics in patients treated with
      R-CHOP.

PMID- 24285020
TI  - Factors influencing adherence to cancer treatment in older adults with cancer: a
      systematic review.
AB  - BACKGROUND: Cancer is a disease that mostly affects older adults. Treatment
      adherence is crucial to obtain optimal outcomes such as cure or improvement in
      quality of life. Older adults have numerous comorbidites as well as cognitive and
      sensory impairments that may affect adherence. The aim of this systematic review
      was to examine factors that influence adherence to cancer treatment in older
      adults with cancer. PATIENTS AND METHODS: Systematic review of the literature
      published between inception of the databases and February 2013. English, Dutch,
      French and German-language articles reporting cross-sectional or longitudinal,
      intervention or observational studies of cancer treatment adherence were
      included. Data sources included MEDLINE, EMBASE, PsychINFO, Cumulative Index to
      Nursing and Allied Health (CINAHL), Web of Science, ASSIA, Ageline, Allied and
      Complementary Medicine (AMED), SocAbstracts and the Cochrane Library. Two
      reviewers reviewed abstracts and abstracted data using standardized forms. Study
      quality was assessed using the Mixed Methods Appraisal Tool 2011. RESULTS: Twenty
      two manuscripts were identified reporting on 18 unique studies. The quality of
      most studies was good. Most studies focused on women with breast cancer and
      adherence to adjuvant hormonal therapy. More than half of the studies used data
      from administrative or clinical databases or chart reviews. The adherence rate
      varied from 52% to 100%. Only one qualitative study asked older adults about
      reasons for non-adherence. Factors associated with non-adherence varied widely
      across studies. CONCLUSION: Non-adherence was common across studies but little is
      known about the factors influencing non-adherence. More research is needed to
      investigate why older adults choose to adhere or not adhere to their treatment
      regimens taking into account their multimorbidity.

PMID- 24285022
TI  - A balancing act: achieving glycemic control in hospitalized patients.

PMID- 24285021
TI  - Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117
      patients: a multicentre observational study by the French ERMETIC-IFCT network.
AB  - BACKGROUND: There is scarce data available about epidermal growth factor receptor
      (EGFR) mutations other than common exon 19 deletions and exon 21 (L858R)
      mutations. PATIENTS AND METHODS: EGFR exon 18 and/or exon 20 mutations were
      collected from 10 117 non-small-cell lung cancer (NSCLC) samples analysed at 15
      French National Cancer Institute (INCa)-platforms of the ERMETIC-IFCT network.
      RESULTS: Between 2008 and 2011, 1047 (10%) samples were EGFR-mutated, 102 (10%)
      with rare mutations: 41 (4%) in exon 18, 49 (5%) in exon 20, and 12 (1%) with
      other EGFR mutations. Exon 20 mutations were related to never-smoker status, when
      compared with exon 18 mutations (P < 0.001). Median overall survival (OS) of
      metastatic disease was 21 months [95% confidence interval (CI) 12-24], worse in
      smokers than in non-smoker patients with exon 20 mutations (12 versus 21 months;
      hazard ratio [HR] for death 0.27, 95% CI 0.08-0.87, P = 0.03). Under EGFR
      tyrosine kinase inhibitors (TKIs), median OS was 14 months (95% CI 6-21); disease
      control rate was better for complex mutations (6 of 7, 86%) than for single
      mutations (16 of 40, 40%) (P = 0.03). CONCLUSIONS: Rare EGFR-mutated NSCLCs are
      heterogeneous, with resistance of distal exon 20 insertions and better
      sensitivity of exon 18 or complex mutations to EGFR-TKIs, probably requiring
      individual assessment.

PMID- 24285023
TI  - Physical training-related changes in gait variability while single and dual
      tasking in older adults: magnitude of gait variability at baseline matters.
AB  - OBJECTIVES: Few studies have examined the effects of physical training programs
      on gait variability while single and dual tasking, and they reported mixed
      results. The aim of this study was to compare the stride time variability while
      single and dual tasking before and after a physical training program developed to
      improve gait stability in French community-dwelling older adults. DESIGN: A
      prospective pre-post interventional cohort study. SETTING: The community-dwelling
      area of "Pays de la Loire", France. POPULATION: Forty-eight older adults (mean
      age +/- standard deviation 72.2+/-8 years; 75% female). METHODS: Physical
      training program consisted in 12 sessions scheduled to attend physical exercises
      1 time a week with total time duration of 3 months. Coefficient of variation
      (CoV) of stride time under three walking conditions (i.e., walking alone, walking
      while backward counting, and while performing a verbal fluency task) was
      determined while steady-state walking using the SMTEC(r) footswitches system
      before and after the physical training program. Participants were separated into
      two groups based on being or not in the highest tertile (i.e., worst performance
      with cutpoint >4.4%) of the CoV of stride time while walking alone. RESULTS:
      After physical training compared to before period, a significant decrease in CoV
      of stride time (i.e., better gait performance) while walking alone (2.8+/-2.8%
      versus 7+/-7.1%, P=0.001) but not while dual tasking (P=0.600 for counting
      backward and P=0.105 for verbal fluency task) was shown in participants who had
      highest (i.e., worst) gait variability at baseline. In addition, physical
      training modified the strategy of dual tasking in participants with highest gait
      variability at baseline compared to the other participants. Before training, a
      significant decrease in CoV of stride time (7+/-7.1% versus 4.9+/-4.6%, P=0.017)
      while counting backward was shown, but there was a significant increase after
      training (2.8+/-2.8% versus 5.4+/-5.8%, P=0.007). CONCLUSIONS: Physical training
      reduced gait variability while walking alone in participants with gait
      instability, and influenced their strategy for dual tasking. CLINICAL
      REHABILITATION IMPACT: Physical program training developed in the community to
      improve gait stability should included participants with high gait variability.

PMID- 24285024
TI  - Rehabilitation for Charcot Marie tooth: a survey study of patients and
      familiar/caregiver perspective and perception of efficacy and needs.
AB  - BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common inherited
      polyneuropathy. At the moment there is no pharmacological therapy for this
      pathology and the conservative treatment is mostly based on rehabilitation
      program. Moreover there is no medical consensus on it and the perception of its
      efficacy is mostly clinician-oriented. AIM: To evaluate, through ad hoc self
      administered questionnaires, the patient and family/caregiver perspective on
      rehabilitation access and perceived benefit from it. DESIGN: Observational survey
      study. SETTING: Clinical and genetic records of in and out-patients of third
      level hospitals and a patients association (ACMT-Rete) and familiar/caregiver.
      POPULATION: Patients affected by CMT and familiar/caregiver. RESULTS:
      Questionnaires showed that patients perceive physical and mental benefit from
      rehabilitation, but also perceived that do not perform the best rehabilitation
      program for their pathology. Familiar and caregiver, are not sure that
      rehabilitation is effective for their kin, probably because the benefits are too
      small to be seen by someone other than the patient. CONCLUSION: The study shows
      as the lack of a consensus on rehabilitation tailored on CMT patients need is
      perceived by patients and familiar/caregiver. CLINICAL REHABILITATION IMPACT: The
      knowledge of patients perception is very important in order to obtain the best
      rehabilitation program for CMT disease.

PMID- 24285025
TI  - The effect of having a children with cerebral palsy on quality of life, burn-out,
      depression and anxiety scores: a comparative study.
AB  - BACKGROUND: The caregivers of children with cerebral palsy (CP) should overcome
      the difficulties and complications arising from their children's impairments. It
      may be stressful for the caregivers when the balance between these inevitable
      demands and their own social needs impairs. Therefore, the primary caregiver, may
      experience several psycho-social problems. AIM: To compare the quality of life
      (QoL), mental health and burnout of caregivers of patients with CP and healthy
      controls. The effects of the functional limitations of children with CP on the
      QoL, mental health and burnout of caregivers have also been evaluated. DESIGN:
      Cross-sectional, comparative. SETTING: Outpatient. POPULATION: One hundred and
      forty-three caregivers of children with CP and 60 caregivers of typically
      developing children were recruited for the study. MATERIALS AND METHODS: The
      inventories related to QoL, mental health and burnout of the caregivers for both
      groups were compared. The correlations between functional limitations of the
      children with CP and QoL, mental health and burnout of their caregivers have been
      analyzed. RESULTS: Caregivers in CP group had poorer QoL, worser mental health,
      and higher burnout levels compared to the controls. The functional limitations of
      the children with CP were correlated with impairment of QoL and depression scores
      of their caregivers, but not with the anxiety or burnout scores. CONCLUSION:
      Having a disabled child has interference on caregivers' QoL and mental health and
      increases the burnout. Furthermore, as the functional impairment level of the
      child increases, the interference does too. Clinical rehabilitation impact.
      Health professionals working in this area should also consider the mental health
      and the QoL of caregivers and should develop interventions that support and
      nurture the family as a whole.

PMID- 24285026
TI  - Neuromuscular electrical stimulation after total joint arthroplasty: a critical
      review of recent controlled studies.
AB  - Since 2009, four randomized controlled trials have investigated the use of
      Neuromuscular Electrical Stimulation (NMES) as a treatment modality following
      total knee arthroplasty (TKA). Two of these studies demonstrated a treatment
      effect of NMES for improving physical function, while another study failed to
      find additional benefit of NMES relative to a progressive exercise intervention.
      The fourth study demonstrated non-inferiority of NMES compared supervised
      physical therapy. These studies differed substantially in their methodology,
      including the timing, duration, treatment volume and intensity of NMES
      interventions. The purpose of this review is to examine and discuss variations
      between these recent trials to synthesize the current state of evidence for NMES
      in post-TKA rehabilitation. When comparing intervention parameters across recent
      studies, it appears that high intensity NMES performed regularly during the
      immediate postoperative phase helped to attenuate dramatic losses in quadriceps
      strength following TKA, thereby resulting in overall improvements in strength and
      function. 

PMID- 24285027
TI  - Osteopathic graduate medical education: a way forward.

PMID- 24285028
TI  - On the oft-debated question of what it means to be an osteopathic physician.

PMID- 24285030
TI  - Preventive osteopathic manipulative treatment and stress fracture incidence among
      collegiate cross-country athletes.
AB  - CONTEXT: Stress fractures are common among athletes, particularly distance
      runners, with many theories regarding the etiologic process of stress fractures
      and various studies identifying risk factors or suggesting preventive techniques.
      To our knowledge, no previous studies have discussed the possible causative
      effects of somatic dysfunction or the preventive capabilities of osteopathic
      manipulative treatment (OMT). OBJECTIVE: To apply a preventive OMT protocol for
      cross-country athletes to reduce the incidence of stress fractures. DESIGN:
      Cohort study. METHODS: Examinations of cross-country athletes at an NCAA
      (National Collegiate Athletic Association) Division I university were performed
      by supervising physician-examiners and first- and second-year osteopathic medical
      students during several consecutive academic years. Athletes re-enrolled in the
      study each year they continued to be eligible. The intervention included
      osteopathic structural examination and OMT that focused on somatic dysfunction
      identified in the pelvis, sacrum, and lower extremities. RESULTS: More than 1800
      participant examinations were performed on 124 male and female participants by 3
      supervising physician-examiners and 141 osteopathic medical students over the
      course of 5 consecutive academic years (2004-2005 to 2008-2009). Data from these
      academic years were compared with data from the previous 8 academic years (1996
      1997 to 2003-2004). An average of 20 new participants enrolled yearly. The number
      of annual stress fractures per team ranged from 0 to 6 for male participants and
      1 to 6 for female participants. The cumulative annual incidence of stress
      fractures for male participants demonstrated a statistically significant decrease
      from 13.9% (20 of 144) before intervention to 1.0% (1 of 105) after intervention,
      resulting in a 98.7% relative reduction in stress-fracture diagnosis (P=.019).
      The cumulative annual incidence for female participants showed a minimal decrease
      from 12.9% (23 of 178) before intervention to 12.0% (17 of 142) after
      intervention, an 8.5% relative reduction in stress-fracture diagnosis (P=.671).
      The cumulative annual incidence of all participants decreased from 13.4% (43 of
      322) before intervention to 7.3% (18 of 247) after intervention, a 45% relative
      reduction in stress-fracture diagnosis (P=.156). CONCLUSION: There was a
      statistically significant decrease in the cumulative annual incidence of stress
      fractures in male, but not female, cross-country athletes after receiving OMT.

PMID- 24285031
TI  - Effect of inpatient electroencephalography on clinical decision making.
AB  - CONTEXT: Routine inpatient electroencephalography (EEG) is commonly used as a
      diagnostic and therapeutic decision-making tool in the care of patients with a
      wide spectrum of conditions. Previous investigations on EEG use have focused on
      current guidelines or specific clinical presentations. OBJECTIVE: To assess the
      effect of EEGs on clinical diagnosis and management of disease in adult
      inpatients in a community hospital. METHODS: Medical records of adult patients
      who underwent EEG between October 2008 and June 2009 in a single general
      community hospital were retrospectively reviewed. Data were collected for
      comorbidities, diagnoses, and management. Findings from EEGs were classified as
      normal, abnormal, or uninterpretable and according to whether they resulted in a
      change in diagnosis or management, supported clinical decision making and
      resulted in no change in diagnosis or management, or did not contribute to
      diagnosis or management. RESULTS: A total of 200 medical records were reviewed;
      110 (55%) were for male patients and 90 (45%) were for female patients, with a
      mean (range) age of 60 (18-96) years. The most common pre-EEG diagnoses were
      altered mental status (52 [26%]) and seizure (48 [24%]). Of all EEGs, 115 (57.5%)
      had findings that were normal, 83 (41.5%) had findings that were abnormal, and 2
      (1%) had findings that were uninterpretable. No EEGs had findings that resulted
      in a change in diagnosis or management, 8 EEGs (4%) had findings that supported
      clinical decision making and resulted in no change in diagnosis or management,
      and 192 EEGs (96%) had findings that did not contribute to diagnosis or
      management. CONCLUSION: In this study, inpatient EEGs rarely contributed to
      clinical decision making and in no case resulted in a change in diagnosis or
      management. These findings warrant future research on the effectiveness of
      inpatient EEGs for a wide breadth of clinical inpatient diagnoses.

PMID- 24285032
TI  - Correlates and changes in empathy and attitudes toward interprofessional
      collaboration in osteopathic medical students.
AB  - CONTEXT: Many studies have reported a decline in empathy as allopathic medical
      students progress through medical school. Data are needed to compare the pattern
      of changes in empathy in osteopathic and allopathic medical students. Also, it is
      important to investigate the associations between measures of empathy and
      attitudes toward interprofessional collaboration, which are among major elements
      of professionalism in medicine. OBJECTIVES: (1) To investigate correlations
      between empathy and interprofessional collaboration in osteopathic medical
      students; (2) to examine differences in empathy and interprofessional
      collaboration scores by sex, class year, and specialty interest; and (3) to
      compare empathy scores by class year between osteopathic and allopathic medical
      students. DESIGN: Correlational and comparative study. SETTING: Ohio University
      Heritage College of Osteopathic Medicine. PARTICIPANTS: Osteopathic medical
      students enrolled in academic year 2011-2012. MAIN OUTCOME MEASURES: The
      Jefferson Scale of Empathy (JSE) and the Jefferson Scale of Attitudes toward
      Physician-Nurse Collaboration (JSAPNC) scores. RESULTS: Student respondents
      (N=373) included 197 women (53%) and 176 men (47%). Significant correlation was
      found between scores on the JSE and JSAPNC (r=0.42, P<.01). Women scored higher
      than men on the JSE (mean scores, 117.1 and 111.9, respectively; F1,371=19.6,
      P<.01) and the JSAPNC (mean scores, 50.1 and 48.7, respectively; F1,371=6.5,
      P<.01). No statistically significant difference on the scores of the 2 scales was
      observed among students who planned to pursue "people-oriented" specialties (150
      [40%]) compared with those interested in "technology/procedure-oriented"
      specialties (170 [45%]). No statistically significant change in empathy scores
      was found in different class years of the osteopathic medical students.
      Comparisons of empathy scores with allopathic medical students showed no
      significant difference in the first and second years, but osteopathic medical
      students had a higher mean empathy score (M=114.4) than their allopathic
      counterparts (M=110.9) in the third year (t158=2.31, P<.05), and their empathy
      scores remained high, although not statistically significant, in the fourth year
      of osteopathic medical school. CONCLUSION: The decline in empathy that is often
      reported among allopathic medical students was not observed. The present study
      can serve as a step toward further longitudinal research on the development of
      empathy and attitudes toward teamwork among osteopathic medical students.

PMID- 24285033
TI  - Axioms, osteopathic culture, and a perspective from geriatric medicine.
AB  - Osteopathic medicine is a rapidly growing discipline in health care that has much
      to offer the wider biomedical community. A distinction of the osteopathic medical
      profession is the importance of an overall guiding philosophy. Despite the
      osteopathic medical profession's success, there remains concern about the
      profession's ability to maintain its unique identity. Among many factors that
      have contributed to the profession's success, certain axioms from its earliest
      days are pertinent to the profession's identity. Maintaining a knowledge and
      appreciation of osteopathic axioms can play an important role in safeguarding the
      profession's identity. These axioms encapsulate osteopathic philosophy and,
      moreover, are universally useful for patient care. As osteopathic geriatricians,
      the authors explore the value and meaning of these axioms for anyone who treats
      patients, but especially for the care of the elderly. The authors also propose a
      new axiom, derived from the experience of 2 of the authors: "First try to blame
      it on the medications." 

PMID- 24285034
TI  - Peer review guidance: how do you write a good review?
AB  - Peer review is essential to the quality of scientific publications. As the volume
      of submissions to these journals increases, the need for an expanding cadre of
      trained reviewers also increases. Many reviewers do not receive formal training
      on conducting a peer review or education on the peer review process, however. The
      author presents an overview of the peer review process and provides guidance for
      conducting high-quality reviews of manuscripts submitted to The Journal of the
      American Osteopathic Association and other scientific journals. 

PMID- 24285035
TI  - Subcutaneous pellet testosterone replacement therapy: the "first steps" in
      treating men with spinal cord injuries.
AB  - The authors describe the case of a 36-year-old man who presented with hormone
      level concerns 6 months after a rock climbing accident that resulted in
      paraplegia. Hypogonadism was diagnosed, and the patient received subcutaneous
      pellet testosterone replacement therapy. Within 6 months, the patient had
      substantial improvement in muscle function and was able to take several steps
      with the assistance of crutches or a walker. This case highlights the potential
      improvement in quality of life and overall prognosis resulting from the
      subcutaneous pellet form of testosterone when used as part of the overall
      treatment plan in such patients. Considering the overwhelming preponderance of
      hypogonadism in men with spinal cord injuries, the standard of care for such
      patients should include screening, laboratory hormone evaluation, and prompt
      treatment for testosterone deficiency. 

PMID- 24285036
TI  - An unexpectedly progressed lumbar herniated disk.
AB  - The authors describe a case of a 26-year-old female military veteran who
      presented with low back pain that she attributed to a recent foot injury. The
      patient reported a history of lumbar pain while in the military that had been
      treated successfully with high-velocity, low-amplitude osteopathic manipulative
      treatment. The patient's current pain was improved with osteopathic manipulative
      treatment and gait correction. Several weeks after her initial presentation, the
      patient reported that she had had a herniated disk diagnosed 2 years earlier by
      means of magnetic resonance imaging. Updated magnetic resonance imaging was
      performed, the results of which revealed a large herniated disk that had caused
      severe stenosis. The patient was immediately referred to a neurosurgeon for
      consultation and subsequently underwent surgical treatment. 

PMID- 24285037
TI  - Pelvic hematoma with suprapubic distention.

PMID- 24285038
TI  - Beyond the medicine.

PMID- 24285040
TI  - Systematic review of emergency laparoscopic colorectal resection.
AB  - BACKGROUND: Laparoscopic surgery (LS) has become standard practice for a range of
      elective general surgical operations. Its role in emergency general surgery is
      gaining momentum. This study aimed to assess the outcomes of LS compared with
      open surgery (OS) for colorectal resections in the emergency setting. METHODS: A
      systematic review was performed of studies reporting outcomes of laparoscopic
      colorectal resections in the acute or emergency setting in patients aged over 18
      years, between January 1966 and January 2013. RESULTS: Twenty-two studies were
      included, providing outcomes for 5557 patients: 932 laparoscopic and 4625 open
      emergency resections. Median (range) operating time was 184 (63-444) min for LS
      versus 148 (61-231) min for OS. Median (range) length of stay was 10 (3-23) and
      15 (6-33) days in the LS and OS groups respectively. The overall median (range)
      complication rate was 27.8 (0-33.3) and 48.3 (9-72) per cent respectively. There
      were insufficient data to detect differences in reoperation and readmission
      rates. CONCLUSION: Emergency laparoscopic colorectal resection, where technically
      feasible, has better short-term outcomes than open resection.

PMID- 24285043
TI  - A new polymorph of lithium manganese(II) pyrophosphate beta-Li2MnP2O7.
AB  - A new polymorph of lithium manganese pyrophosphate was synthesized by low
      temperature solid-state synthesis, and the crystal structure was determined. The
      new phase has a new type of three-dimensional framework structure, which is
      completely different from that found in the previous study by Adam et al., J.
      Solid State Chem., 2008, 181, 3110. Electrochemical measurement with a Li cell
      demonstrated a reversible electrochemical activity at around 4 V. 

PMID- 24285042
TI  - Telomere length as a risk factor for hereditary prostate cancer.
AB  - BACKGROUND: Telomeres are repetitive nucleotide sequences that stabilize the ends
      of chromosomes. Critically short telomeres are thought to contribute to cancer
      development by increasing chromosomal instability. We hypothesized that shorter
      leukocyte telomere length, a surrogate for inherited prostate cell telomere
      length, would be associated with increased risk of prostate cancer in hereditary
      prostate cancer (HPC) families. METHODS: One hundred twelve affected and 63
      unaffected men from 28 families were drawn from the Johns Hopkins HPC family
      database. Relative mean telomere length was measured in isolated peripheral
      leukocyte DNA by quantitative PCR. Conditional logistic regression was used to
      estimate the association between quartile of age-adjusted telomere length and
      prostate cancer. RESULTS: Men in the shortest quartile of telomere length did not
      have increased odds of prostate cancer compared to men in the other three
      quartiles (OR = 0.84, 95% CI: 0.32-2.20, P = 0.73). However, when the analysis
      was restricted to affected men with blood drawn before or within a year of
      diagnosis (N = 39) and all unaffected men, shorter telomere length was moderately
      associated with increased odds of prostate cancer (OR = 3.55, 95% CI: 0.82-15.43,
      P = 0.09). CONCLUSIONS: Though we found no association overall, shorter leukocyte
      telomere length may be associated with increased odds of prostate cancer when
      measured in pre-diagnostic samples. Further prospective research is warranted
      exploring the utility of telomere length as a prostate cancer biomarker.

PMID- 24285044
TI  - Angiotensin-converting enzyme inhibitor-induced angioedema--a dangerous new
      epidemic.
AB  - Angioedema is a sudden localised and often asymmetric swelling of the skin or
      mucous membranes caused by transient increased endothelial permeability causing
      plasma extravasation. In the last decades the incidence of severe angioedema
      involving the upper airways and even fatal outcome due to asphyxia has increased.
      This is mainly due to pharmaceuticals such as angiotensin converting enzyme
      inhibitors, which are extensively used worldwide. Some aspects of the
      pathophysiology have been elucidated and the vasoactive molecule bradykinin is
      shown to be one of the main causative agents. The diagnosis is often delayed and
      traditional treatment usually ineffective. Complement C1 inhibitor concentrate
      and bradykinin receptor antagonists, normally used to treat patients with
      hereditary angioedema, have shown good results when used in patients with
      bradykinin-mediated angioedema. This review discusses the disease, prognosis and
      treatment options. 

PMID- 24285045
TI  - Endoscopic treatment of a solitary hamartomatous polyp in the intrahepatic
      biliary duct.

PMID- 24285046
TI  - Fatal cerebral air embolism complicating esophageal dilation.

PMID- 24285047
TI  - Single-operator cholangioscopy for the diagnosis of bile duct lymphoma: a case
      report and brief review of the literature.

PMID- 24285048
TI  - Pancreatic stent eroding into the stomach.

PMID- 24285049
TI  - Formalin-induced severe colonic necrosis.

PMID- 24285050
TI  - Resection of carcinoids in the duodenal bulb using the band ligation technique
      with the Duette mucosectomy device.

PMID- 24285051
TI  - Intermittent abdominal pain due to pancreatic pseudocyst hemorrhage diagnosed by
      endoscopic ultrasound.

PMID- 24285052
TI  - Balloon overtube-assisted placement of self-expanding metal stents.

PMID- 24285053
TI  - Removal of a migrated gastric band using the Soehendra bile stone lithotripter.

PMID- 24285054
TI  - A calibrated, small-caliber tip, transparent hood to aid endoscopic balloon
      dilation of intestinal strictures in Crohn's disease: successful use of
      prototype.

PMID- 24285055
TI  - A "tuft" procedure.

PMID- 24285056
TI  - Giant villous duodenal adenoma with malignant change: an unusual cause of
      obstructive jaundice.

PMID- 24285057
TI  - Calcium polystyrene sulfonate bezoar in the ileum: diagnosis and treatment with
      double-balloon endoscopy.

PMID- 24285058
TI  - Post-transplant lymphoproliferative disorder of the ileum diagnosed by double
      balloon enteroscopy.

PMID- 24285059
TI  - Cysto-duodenal fistula: an unusual complication of a nonparasitic hepatic cyst.

PMID- 24285060
TI  - Combined endoclipping and argon plasma coagulation (APC)--daisy technique for
      cecal angiodysplasia.

PMID- 24285061
TI  - Endoscopic diagnosis and treatment of a giant duodenal lipoma presenting with
      gastrointestinal bleeding.

PMID- 24285062
TI  - A new attachment hood (Nanoshooter) for transnasal endoscopic submucosal
      dissection of the hypopharynx.

PMID- 24285063
TI  - Assessment of the early regenerative therapeutic response in graft versus host
      disease using high definition technology with virtual i-Scan chromoendoscopy.

PMID- 24285064
TI  - Gastric rupture as a rare complication in diagnostic upper gastrointestinal
      endoscopy.

PMID- 24285065
TI  - Closure with an over-the-scope clip allows therapeutic ERCP to be safely
      performed after acute duodenal perforation during diagnostic endoscopic
      ultrasound.

PMID- 24285066
TI  - Persistent peristomal leakage from percutaneous endoscopic gastrostomy
      successfully treated with endoscopic suturing.

PMID- 24285067
TI  - Endoscopic treatment of an infected retroperitoneal hematoma following endoscopic
      ultrasound-guided pseudocyst drainage.

PMID- 24285068
TI  - Avulsion of the papilla of Vater managed using a rendezvous technique and extra
      anatomic drainage.

PMID- 24285069
TI  - Intrauterine foreign body presenting as a rectal bezoar and causing chronic
      diarrhea.

PMID- 24285070
TI  - Diaphragmatic hernia: a rare adverse event of colonoscopy.

PMID- 24285071
TI  - Infected hepatic hematoma 10 days after ERCP.

PMID- 24285072
TI  - Bile leak from the duct of Luschka treated with double-balloon enteroscopy ERCP
      in a patient with Roux-en-Y gastric bypass.

PMID- 24285073
TI  - Fatal mediastinitis following botulinum toxin injection for esophageal spasm.

PMID- 24285074
TI  - Diffuse replacement of pancreatic parenchyma by intraductal papillary mucinous
      neoplasm.

PMID- 24285075
TI  - Successful removal from the esophagus of a self-expandable metal stent that had
      shriveled up into a tangled ball.

PMID- 24285076
TI  - Bezoar formation and obstruction caused by a surgical nylon thread after gastric
      bypass surgery.

PMID- 24285077
TI  - Use of a homemade endoscopic guillotine to cut through a nasogastric tube
      inadvertently sutured to a colon-gastric anastomosis.

PMID- 24285078
TI  - Complete small-bowel examination by oral single-balloon enteroscopy using the
      water-exchange method.

PMID- 24285079
TI  - Overtube-assisted placement of a metal stent into the bile duct of a patient with
      surgically altered upper-gastrointestinal anatomy during double-balloon
      enteroscopy-assisted ERCP.

PMID- 24285080
TI  - Abstract rule neurons in the endbrain support intelligent behaviour in corvid
      songbirds.
AB  - Despite the lack of a layered neocortex and fundamental differences in endbrain
      organization in birds compared with mammals, intelligent species evolved from
      both vertebrate classes. Among birds, corvids show exceptional cognitive
      flexibility. Here we explore the neuronal foundation of corvid cognition by
      recording single-unit activity from an association area known as the nidopallium
      caudolaterale (NCL) while carrion crows make flexible rule-guided decisions, a
      hallmark of executive control functions. The most prevalent activity in NCL
      represents the behavioural rules, while abstracting over sample images and
      sensory modalities of the rule cues. Rule coding is weaker in error trials, thus
      predicting the crows' behavioural decisions. This suggests that the abstraction
      of general principles may be an important function of the NCL, mirroring the
      function of primate prefrontal cortex. These findings emphasize that intelligence
      in vertebrates does not necessarily rely on a neocortex but can be realized in
      endbrain circuitries that developed independently via convergent evolution. 

PMID- 24285081
TI  - Regulatory mechanisms and pathophysiological significance of IP3 receptors and
      ryanodine receptors in drug dependence.
AB  - Calcium is a ubiquitous intracellular signaling molecule required for initiating
      and regulating neuronal functions. Ca(2+) release from intracellular stores in
      the endoplasmic reticulum into intracellular spaces via intracellular Ca(2+)
      releasing channels, inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine
      receptors (RyRs), is one mechanism altering the intracellular Ca(2+)
      concentration. Functional abnormalities in endoplasmic calcium channels can
      disturb cellular calcium homeostasis and, in turn, produce pathological
      conditions. Indeed, our recent studies have indicated the involvement of these
      upregulated calcium channels in development of the rewarding effect of a drug of
      abuse and the suppression of its rewarding effect by calcium-channel inhibitors,
      which suggests a possible functional relationship between intracellular dynamics
      and the development of the rewarding effects induced by an abused drug. Although
      previous reports showed that the most important regulators of both RyR and IP3R
      channel functions are changes in the intracellular Ca(2+) concentration and in
      phosphorylation of these channels by numerous kinases and calcium modulators,
      little information is available to clarify how the expression of intracellular
      calcium channels is regulated. In this review, we therefore introduce the roles
      and regulatory mechanisms of intracellular calcium channels in drug dependence,
      especially in the rewarding effect induced by the abused drug. 

PMID- 24285082
TI  - HMGB1 as a potential therapeutic target for neuropathic pain.
AB  - Neuropathic pain, which is intolerable and persistent, arises as a direct
      consequence of a lesion or disease affecting the somatosensory system and can be
      debilitating for the affected patients. Accumulating evidence from animal studies
      has revealed the potential molecular basis for neuropathic pain, resulting in
      many promising therapeutic targets. While efforts at drug discovery have been
      made, conventional pharmacotherapy, including the use of opioid analgesics, is
      still insufficient for the relief of neuropathic pain. Therefore, novel target
      molecules that may lead to the development of promising analgesics are eagerly
      anticipated for improved treatment of neuropathic pain. In various insults such
      as sepsis and ischemia, high-mobility group box 1 (HMGB1) is released
      extracellularly to induce inflammation. HMGB1 was originally identified as a
      ubiquitous nuclear protein, but emerging evidence has suggested that HMGB1 also
      plays a role in neuroinflammation as a pro-inflammatory mediator. These findings
      suggest that HMGB1 may be involved in the pathology of neuropathic pain. In fact,
      some reports demonstrate an involvement of HMGB1 in the development and
      maintenance of neuropathic pain in experimental animals. Here, we overview the
      characteristics of HMGB1 as a pro-inflammatory mediator and show the promise of
      HMGB1 as a therapeutic target for neuropathic pain. 

PMID- 24285083
TI  - Dual role of nitric oxide in pancreatic beta-cells.
AB  - An involvement of inducible nitric oxide (NO) synthase (NOS) in pancreatic beta
      cell degeneration during the process of type 1 diabetes has been well discussed.
      Recently, there is growing evidence for pivotal roles of constitutive NOS (cNOS)
      in beta-cells; the presence of NOS1 and NOS3 in pancreatic beta-cells and the
      effects of low-concentration NO, which is assumed to be derived from cNOS, on
      beta-cell functions have been reported. However, the roles of cNOS-derived NO in
      beta-cells are still under debate. One of the reasons seems to be that NO has
      multiple biological activities, which are dependent on its concentration. In beta
      cells, NO has been shown to exert positive and negative regulation of insulin
      secretion and anti- and pro-apoptotic activities, which is likely to be dependent
      on concentrations. In this review article, we will describe the current
      understanding of the roles of NO in pancreatic beta-cells, especially focusing on
      cNOS-derived NO and its differential roles depending on concentrations. 

PMID- 24285084
TI  - Influence of membrane composition on the enhancement of factor VIIa/tissue factor
      activity by magnesium ions.

PMID- 24285085
TI  - Assessing health-related quality of life for advanced basal cell carcinoma and
      basal cell carcinoma nevus syndrome: development of the first disease-specific
      patient-reported outcome questionnaires.
AB  - IMPORTANCE Little is known about patients' experiences of advanced basal cell
      carcinoma (aBCC) and basal cell carcinoma nevus syndrome (BCCNS), a rare genetic
      disorder that greatly increases the number of BCCs. OBJECTIVE To develop a
      questionnaire to measure patient-reported outcomes (PROs) in these populations.
      DESIGN, SETTING, AND PARTICIPANTS Concept elicitation interviews were conducted
      with patients with aBCC and BCCNS from 5 US clinical sites and the BCCNS Life
      Support Network and 4 physicians. The PRO questionnaires were drafted based on
      results from a literature review and findings from these interviews.
      Questionnaires were finalized after cognitive debriefing interviews were
      conducted with patients. Concept elicitation interviews were conducted with 30
      patients (14 with aBCC, 16 with BCCNS) and 4 physicians (2 dermatologists, 1 Mohs
      surgeon, and 1 oncologist) in the United States. A subset of 10 of these patients
      (5 with aBCC, 5 with BCCNS) took part in cognitive debriefing interviews. MAIN
      OUTCOMES AND MEASURES Development of 2 questionnaires to allow clinicians to
      assess the emotional, social, and physical impacts of the disease on patients
      with aBCC and BCCNS. RESULTS Most concept elicitation interview patients were
      male (63%) and white (93%); their mean age was 57 years. There were impacts on
      emotional, social, and physical functioning in both conditions. Patients were
      unable to do many activities and avoided other activities. Seventy-nine percent
      of patients with aBCC and all patients with BCCNS reported scarring. Physician
      interviews revealed similar findings. During cognitive debriefing interviews, the
      questionnaires were found to be relevant, clear, and comprehensive. CONCLUSIONS
      AND RELEVANCE Advanced BCC and BCCNS affect patients in unique and substantial
      ways. These PRO questionnaires were developed with patient and clinician input
      and measure the key areas that have an impact on patients with these conditions. 

PMID- 24285087
TI  - Complex force dynamics in atomic force microscopy resolved by wavelet transforms.
AB  - The amplitude and phase evolution of the oscillations of a cantilever after a
      single tip-sample impact are investigated using a cross-correlation wavelet
      analysis. The excitation of multiple flexural modes is evidenced and the
      instantaneous amplitude and phase evolution is extracted from the experimental
      data at all frequencies simultaneously. The instantaneous total force acting on
      the tip during a single impact is reconstructed. This method has general
      relevance for the development of an atomic force spectroscopy of single tip
      sample interactions, that develop in a few oscillation cycles of the interacting
      cantilever eigenmodes and their harmonics. 

PMID- 24285088
TI  - Genomic analysis of a phage and prophage from a Bacillus thuringiensis strain.
AB  - Bacteriophages have been found to be the most abundant and also potentially most
      diverse biological entities on Earth. In the present study, Bacillus phages were
      isolated rapidly and shown to have a high degree of diversity. The genomes of a
      newly isolated phage, phiCM3, and a prophage, proCM3, from the Bacillus
      thuringiensis strain YM-03 were sequenced and characterized. Comparative genome
      analysis showed that the phiCM3 genome is highly similar to the genomes of eight
      other Bacillus phages and seven of these phages were classified as the Wbeta
      group of phages. Analysis of the differential evolution of the genes in the Wbeta
      group phages indicated that the genes encoding the antirepressor and tail fibre
      protein were more highly conserved than those encoding the major capsid protein,
      DNA replication protein, and RNA polymerase sigma factor, which might have
      diverged to acquire mechanisms suitable for survival in different microbial
      hosts. Genome analysis of proCM3 revealed that proCM3 might be a defective phage
      because of mutations in the minor structural protein, and it was not inducible by
      mitomycin C treatment. The proCM3 genome was similar to those of two lytic
      Bacillus phages in sequence, but had a different genomic structure, composed of
      three regions in a different order. These data suggest that the three phages
      might have had a common ancestor and that genome rearrangement might have
      occurred during evolution. The findings of this study enrich our current
      knowledge of Bacillus phage diversity and evolution, especially for the Wbeta
      group and TP21-L-like phages, and may help the development of practical
      applications of Bacillus phages. 

PMID- 24285089
TI  - Early-warning signals of topological collapse in interbank networks.
AB  - The financial crisis clearly illustrated the importance of characterizing the
      level of 'systemic' risk associated with an entire credit network, rather than
      with single institutions. However, the interplay between financial distress and
      topological changes is still poorly understood. Here we analyze the quarterly
      interbank exposures among Dutch banks over the period 1998-2008, ending with the
      crisis. After controlling for the link density, many topological properties
      display an abrupt change in 2008, providing a clear - but unpredictable -
      signature of the crisis. By contrast, if the heterogeneity of banks' connectivity
      is controlled for, the same properties show a gradual transition to the crisis,
      starting in 2005 and preceded by an even earlier period during which anomalous
      debt loops could have led to the underestimation of counter-party risk. These
      early-warning signals are undetectable if the network is reconstructed from
      partial bank-specific data, as routinely done. We discuss important implications
      for bank regulatory policies. 

PMID- 24285091
TI  - The bitter pill: clinical drugs that activate the human bitter taste receptor
      TAS2R14.
AB  - Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is
      often bitter. These G-protein-coupled receptors are also expressed in extraoral
      tissues, and emerge as novel targets for therapeutic indications such as asthma
      and infection. Our goal was to identify ligands of the broadly tuned TAS2R14
      among clinical drugs. Molecular properties of known human bitter taste receptor
      TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and
      used to computationally predict additional ligands. Predictions were tested by
      calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the
      virtual screening predictions resulted in 30-80% success rates, and 15 clinical
      drugs were found to activate the TAS2R14. hERG potassium channel, which is
      predominantly expressed in the heart, emerged as a common off-target of bitter
      drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands
      and previously unknown polypharmacology of drugs were unraveled by in vitro
      screening of computational predictions. This enables rational repurposing of
      traditional and standard drugs for bitter taste signaling modulation for
      therapeutic indications.

PMID- 24285090
TI  - Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by
      vanadium pentoxide (V2O5).
AB  - Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and
      scarring of alveoli, leading to impaired function. The etiology of idiopathic
      forms of ILD is not understood, making them particularly difficult to study due
      to the lack of appropriate animal models. Consequently, few effective therapies
      have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide
      (V2O5), the most common form of a transition metal found in cigarette smoke, fuel
      ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose
      dependent increases in lung permeability, inflammation, collagen content, and
      dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice.
      Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while
      limited responses in C57BL/6J mice resolved. We investigated the genetic basis
      for differential responses through genetic mapping of V2O5-induced lung collagen
      content in BXD recombinant inbred (RI) strains and identified significant linkage
      on chromosome 4 with candidate genes that associate with V2O5-induced collagen
      content across the RI strains. Results suggest that V2O5 may induce pulmonary
      fibrosis through mechanisms distinct from those in other models of pulmonary
      fibrosis. These findings should further advance our understanding of mechanisms
      involved in ILD and thereby aid in identification of new therapeutic targets.

PMID- 24285092
TI  - Nitric oxide is required for homeostasis of oxygen and reactive oxygen species in
      barley roots under aerobic conditions.

PMID- 24285093
TI  - Mechano-stimulation triggers turgor changes associated with trap closure in the
      Darwin plant Dionaea muscipula.

PMID- 24285094
TI  - Cysteine and cysteine-related signaling pathways in Arabidopsis thaliana.
AB  - Cysteine occupies a central position in plant metabolism because it is a reduced
      sulfur donor molecule involved in the synthesis of essential biomolecules and
      defense compounds. Moreover, cysteine per se and its derivative molecules play
      roles in the redox signaling of processes occurring in various cellular
      compartments. Cysteine is synthesized during the sulfate assimilation pathway via
      the incorporation of sulfide to O-acetylserine, catalyzed by O
      acetylserine(thiol)lyase (OASTL). Plant cells contain OASTLs in the mitochondria,
      chloroplasts, and cytosol, resulting in a complex array of isoforms and
      subcellular cysteine pools. In recent years, significant progress has been made
      in Arabidopsis, in determining the specific roles of the OASTLs and the
      metabolites produced by them. Thus, the discovery of novel enzymatic activities
      of the less-abundant, like DES1 with L-cysteine desulfhydrase activity and SCS
      with S-sulfocysteine synthase activity, has provided new perspectives on their
      roles, besides their metabolic functions. Thereby, the research has been
      demonstrated that cytosolic sulfide and chloroplastic S-sulfocysteine act as
      signaling molecules regulating autophagy and protecting the photosystems,
      respectively. In the cytosol, cysteine plays an essential role in plant immunity;
      in the mitochondria, this molecule plays a central role in the detoxification of
      cyanide, which is essential for root hair development and plant responses to
      pathogens. 

PMID- 24285095
TI  - Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus
      erythematosus patients.
AB  - The clearance of apoptotic cells has an important role in the maintenance of
      tissue homeostasis and in the protection of tissues from the inflammatory and
      immunogenic contents of dying cells. A defect in the recognition and phagocytosis
      of apoptotic cells contributes to the development of chronic inflammation and
      autoimmune disorders. We have observed that compared with healthy donors,
      differentiated macrophages from patients with untreated systemic lupus
      erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A
      TaqMan Low Density Array was designed to determine the mRNA expression levels of
      95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing
      macrophages. In the macrophages of clinically and immunoserologically active SLE
      patients, 39 genes were expressed at lower levels than in the control
      macrophages. When inactive patients were compared with those with minor
      immunoserological abnormalities or patients in an immunoserologically active
      state, a relationship was observed between the altered gene expression profile
      and the disease state. In the macrophages of patients with engulfing apoptotic
      cells, an upregulation of genes involved in inflammation, autophagy, and
      signaling was observed. These results indicate that novel immune-pathological
      pathways are involved in SLE and suggest targets for potential therapeutic
      modulation.

PMID- 24285096
TI  - Collapsing glomerulopathy in collagen vascular-like disease.
AB  - OBJECTIVE: Collapsing glomerulopathy (CG) is a podocytopathy that is usually
      associated with human immunodeficiency virus (HIV) and parvovirus B19 infections.
      CG has been reported in association with definite collagen vascular diseases,
      mainly systemic lupus erythematosus (SLE). There are a few case reports in the
      nephrology literature of patients with CG and marked serological abnormalities
      who do not have sufficient clinical findings to diagnose definite collagen
      vascular disease. We wish to expand the spectrum of rheumatologic disease that
      accompanies CG. We describe four patients with CG and collagen vascular-like
      disease and compare these with 14 similar cases reported in the medical
      literature. METHODS: Case reports of four new patients with CG and collagen
      vascular-like disease are presented. We performed a systematic literature review
      to find all other cases and construct a profile of patients with CG and collagen
      vascular-like disease. RESULTS: All patients had a similar mode of presentation
      with severe nephrotic range proteinuria and renal insufficiency resistant to
      steroids and usual immunomodulatory therapy. All patients had positive
      antinuclear antibodies (ANA) as well as other marked serological abnormalities
      but few if any clinical findings that would allow for a definitive diagnosis of a
      specific collagen vascular disease. Almost all patients became dialysis
      dependent. Mycophenolate mofetil (MMF) may possibly be a therapeutic option.
      CONCLUSION: Rheumatologists may be asked to consult on patients with severe
      proteinuria and renal insufficiency in the presence of marked serological
      abnormalities but few clinical symptoms and should be aware of this
      podocytopathy.

PMID- 24285097
TI  - Lymphocyte sensitivity assay as a marker for glucocorticoid resistance in lupus:
      report of two sisters with systemic lupus erythematosus.
AB  - Glucocorticoid sensitivity can be measured in vitro using the lymphocyte
      sensitivity assay (LSA). In this test, dexamethasone is used to inhibit the
      proliferation of peripheral blood mononuclear cells (PBMC) in response to
      mitogens. If the proliferation of PBMC is suppressed the subjects are considered
      to be GC sensitive; if not, they are considered to be resistant. The LSA has been
      used to test GC sensitivity in some inflammatory diseases but its clinical value
      in systemic lupus erythematosus (SLE) has not been determined. Herein, we present
      the results of the LSA from two sisters with SLE who had different disease
      outcomes. Patient 1 presented with higher disease activity and damage accrual,
      and poorer response to corticosteroids than patient 2. In the LSA, patient 1 had
      a lower dexamethasone suppression of mitogen-stimulated PBMC than patient 2 and
      one control subject. The LSA could be helpful in identifying patients with GC
      resistance, thus allowing the consideration of alternative immunosuppressive
      drugs. 

PMID- 24285098
TI  - The American College of Rheumatology and the Systemic Lupus International
      Collaborating Clinics classification criteria for systemic lupus erythematosus in
      two multiethnic cohorts: a commentary.
AB  - The authors offer some comments on the advantages and possible drawbacks of using
      the SLICC criteria in longitudinal observational studies and clinical trials
      after applying and comparing them to the ACR criteria in two multinational,
      multiethnic lupus cohorts. 

PMID- 24285099
TI  - Dual function of MyD88 in inflammation and oncogenesis: implications for
      therapeutic intervention.
AB  - PURPOSE OF REVIEW: Inflammation is emerging as a new hallmark of cancer, and the
      toll-like receptor and interleukin-1 receptor adaptor molecule MyD88 has been
      linked to tumorigenesis. The purpose of this review is to give a brief overview
      of the latest advances in understanding the complexity of MyD88 implication in
      tumorigenesis. RECENT FINDINGS: MyD88 is shown to play a protumorigenic role
      through two mechanisms. First, it activates the nuclear factor kappa-light-chain
      enhancer of activated B cells signaling pathway in the hematopoietic compartment
      and in tumor cells, inducing an inflammatory environment favorable to
      carcinogenesis. Second, it plays a cell-autonomous role in Ras signaling and
      transformation, independently of its role in inflammatory signaling. MyD88
      mediates the optimal activation of the Ras/extracellular signal-regulated kinase
      (ERK) pathway by binding to ERK and protecting it from dephosphorylation. This
      optimal activation of the Ras pathway is essential for the expression of
      important DNA repair enzymes, allowing cancer cells to efficiently repair damaged
      DNA. MyD88 is also shown in certain cases to play an antitumoral role through
      modulation of the immune response SUMMARY: These findings present a new dual
      function model for MyD88 implication in carcinogenesis making it a potential
      therapeutic target in cancer.

PMID- 24285101
TI  - Reply: To PMID 23729294.

PMID- 24285102
TI  - Management of pregnancy in women with type 1 diabetes.
AB  - Type 1 diabetes is increasingly common, thus affecting more women of childbearing
      potential. Inadequate glycemic control complicates pregnancy and can result in
      significant morbidity and mortality. Fetal consequences include congenital
      malformations, recurrent miscarriages, growth anomalies and stillbirth. Maternal
      consequences include worsening of diabetes vascular complications, pre-eclampsia,
      eclampsia and increased likelihood of caesarian section. Hence, pregnancies
      should be carefully planned in advance and managed by a multi-disciplinary team
      of experienced diabetologists, diabetes educators, and maternal-fetal medicine
      specialists. Educating the patient is the cornerstone of care. Preventing
      unplanned pregnancies, particularly in the context of uncontrolled diabetes,
      excellent glycemic control in the months leading to discontinuation of birth
      control, recognition and stabilization of associated co-morbidities and diabetic
      complications are some of the measures shown to improve pregnancy outcome in
      diabetes. During pregnancy, glycemic targets are typically set lower than the non
      pregnant state (i.e., fasting blood glucose <90 mg/dL [5.0 mmol/L] and peak, 1 h
      post-prandial <120 mg/dL [6.7 mmol/L]) with a target glycated hemoglobin close to
      or possibly lower than 6%. Several insulin analogues are now approved for use in
      pregnancy, facilitating insulin administration, while many patients elect insulin
      pump therapy (with or without the addition of continuous glucose monitor
      sensing). Stringent glucose control is maintained through labor, and insulin
      requirements decrease to pre-pregnancy levels after delivery. Women who choose to
      pursue breastfeeding should be encouraged to do so, and supported by minimizing
      mother/baby separation and providing access to a lactation specialist. 

PMID- 24285100
TI  - New insights in risk stratification of differentiated thyroid cancer.
AB  - PURPOSE OF REVIEW: Numerous staging and scoring systems exist for differentiated
      thyroid cancer (DTC), but all harbor limitations. This has prompted investigation
      for new factors with prognostic implications for DTC. RECENT FINDINGS: Several
      new factors that may be involved in DTC risk stratification have emerged, such as
      thyroid stimulating hormone and molecular markers. In addition, others are
      controversial and being challenged, such as age, sex and lymph node involvement.
      SUMMARY: The purpose of this review is to present recent updates in the
      literature on new potential risk stratification predictors for DTC.

PMID- 24285103
TI  - Management of prolactinomas during pregnancy.
AB  - Prolactinomas constitute approximately 40% of hormone-secreting pituitary tumors.
      In women the main clinical features are menstrual disorders and infertility.
      Successful treatment with dopamine agonists restores the normal function of the
      pituitary-gonadal axis, ovulation, and fertility. Adequate management of pregnant
      prolactinoma patients from the moment of conception is of particular importance
      for both the mother and the developing fetus. This review article presents
      current opinions on the course and management of pregnancies in patients with
      prolactin-secreting pituitary tumors. The introduction contains background
      information on clinical aspects of the condition, including prolactinoma
      treatment in women of reproductive age. Physiological changes in the pituitary
      during normal pregnancy are also described. The next part presents current
      knowledge on the effect of pregnancy on prolactinoma size, including especially
      the high risk of prolactinoma growth in patients with pituitary macroadenomas.
      Safety issues concerning the use of dopamine receptor agonists during pregnancy
      are also discussed, especially in terms of the risk of congenital defects in the
      fetus. Moreover, the article presents principles of prolactinoma management in
      pregnant patients, rare indications for surgical treatment during pregnancy, and
      the issues concerning pituitary tumor apoplexy in pregnant women, the last being
      a life-threatening condition. The final part of the article discusses the
      possible effects of pregnancy on hyperprolactinemia remission as well as on the
      issue of breastfeeding by mothers with prolactinoma. 

PMID- 24285104
TI  - Hypothyroidism and depression: salient aspects of pathogenesis and management.
AB  - Hypothyroidism has been linked to depression as there is irrefutable evidence
      that it triggers affective disease and psychic disorders. Depressive patients
      have a higher frequency of hypothyroidism and patients with hypothyroidism have a
      higher occurrence of depressive syndrome. Hypothyroidism exhibits considerable
      alterations in blood flow and glucose metabolism in the brain. Furthermore,
      patients with major depression may have structural abnormalities of the
      hippocampus that can affect memory performance. Thyroid peroxidase antibodies
      have, moreover, been positively associated with trait markers of depression.
      Depressive symptomatology is variable and is influenced by susceptibility and the
      degree, though not always, of thyroid failure. In addition, glucose homeostasis
      and rapid weight loss have been associated to thyroid hormones and increased
      depressive symptoms. Thyroxine treatment in patients older than 65 years does not
      improve cognition. In contrast, T3 administration is the therapy of choice in
      patients with resistance to antidepressive drugs, and especially to SSIR. Genetic
      variants of thyroid hormone transporters or of deiodinases I and II may
      predispose to depression and, therefore, a personalized approach should be
      implemented. 

PMID- 24285105
TI  - Anesthetic-induced transient hyperglycemia and insulin resistance do not depend
      on the sympathoadrenal axis.
AB  - AIM: Glucose homeostasis is maintained under strict physiological control in
      which the central nervous system is very important. Ketamine/xylazine mixture
      induces hyperglycemia, although the mechanism involved is unknown. We aimed to
      study the role of sympathoadrenal axis on glycemia and insulinemia in adult rats.
      METHODS: NInety-day-old male Wistar rats were used. Half of the rats underwent
      removal of the adrenal gland medullae (adrenodemedullation, ADM). After overnight
      fasting, all rats were given the intravenous glucose tolerance test (ivGTT),
      which was performed in six groups: awake, ketamine/xylazine (KX) and thiopental
      (Thiop) anesthetized intact rats, and the same groups of ADM rats. The
      intraperitoneal insulin tolerance test (1U/kg BW) was performed in an additional
      animal group to record the rate constant of plasma glucose disappearance (Kitt).
      Tissue insulin sensitivity was also evaluated by the homeostasis model assessment
      (HOMA). RESULTS: Ketamine/xylazine increased basal glycemia by 110.6% (P<0.001)
      in intact rats. In the ADM group, KX rats had a reduction of 36.6% (P<0.05) basal
      glycemia. Thiop caused a decrease of 70.3% (P<0.05) in basal insulinemia in
      intact rats. ADM reduced fasting insulin in all groups. Insulin sensitivity was
      elevated in intact Thiop rats, while insulin resistance was observed in intact KX
      rats. Both anesthetics induced glucose intolerance during ivGTT in the intact
      group, but not in ADM rats. Insulin secretion was reduced for both anesthetics in
      intact and ADM rats. CONCLUSION: Sympathoadrenal axis activity is not involved
      with the hyperglycemia induced by thiopental or ketamine/xylazine.

PMID- 24285106
TI  - Impact of cinacalcet hydrochloride in clinical management of primary
      hyperparathyroidism in multiple endocrine neoplasia type 1.
AB  - AIM: Primary hyperparathyroidism (PHPT) is one of main cause of morbidity in
      patients with multiple endocrine neoplasia type 1 (MEN1). Medical therapy with
      cinacalcet-hydrochloride may modify the therapeutic strategy of MEN1 related
      PHPT. We present an experience with cinacalcet-hydrochloride in two patients with
      MEN1 PHPT. METHODS: The study included two MEN1 patients belonging to the same
      family (a 50-year-old woman and her daughter aged 20 years) with PHPT secondary
      to multiple involvement of parathyroid glands and other MEN1 related tumors. As
      both patients refused to undergo parathyroid surgery, we decided to start medical
      treatment with cinacalcet at the dose of 30 mg/day, which was the first treatment
      for the youngest patient, while the oldest had already been treated with partial
      parathyroidectomy. Serum concentrations of PTH, calcium and phosphorus, 24-h
      urine calcium-to-creatinine ratio and renal-threshold-phosphate concentration
      were evaluated before and after therapy. RESULTS: Serum calcium and PTH levels
      were normalized after 1 and 6 months of therapy, respectively, and 60 and 54
      months after the beginning of cinacalcet remained normal. Hypercalciuria,
      hypophosphoremia and renal-threshold-phosphate normalized during therapy with
      cinacalcet. At ultrasonography, parathyroid nodular lesion remained unchanged.
      Cinacalcet was well tolerated without occurrence of side effects. CONCLUSION:
      Cinacalcet seems to be highly effective in controlling PHPT in patients with MEN1
      either in naive patients or in those with postsurgical recurrence. If cinacalcet
      will be confirmed to ensure a long-time control of PHPT or even to prevent the
      development and progression of PHPT, this may led to modify the therapeutic
      strategy of MEN1 PHPT.

PMID- 24285107
TI  - The effect of resistance training on plasma S1P level and gene expression of
      S1P1,2,3 receptors in male Wistar rats.
AB  - AIM: The purpose of present study was to study the effect of 8 weeks resistance
      training on plasma Sphingosine-1-phosphate (S1P) level and gene expression of S1P
      receptors in skeletal muscles of male Wistar rat. METHODS: In this study 24 (8
      week-old) male Wistar rats (190-250 gr) were divided randomly to a control
      (N.=12) and a training (N.=12) group. Resistance ladder was 1 meter height with 2
      cm grid ladder. The content of plasma S1P and relative mRNA expression of S1P
      receptors were determined by high pressure liquid chromatography (HPLC) and Real
      time PCR, respectively. RESULTS: Resistance training increased the content of
      plasma S1P of exercised group compared to control group (P=0.001). Furthermore,
      Resistance exercise training increased the gene expression of S1P1 (P=0.001),
      S1P2 (P=0.000) and S1P3 receptors (P=0.021) in exercised flexor hallucis longus
      (FHL) compared to control group. In soleus (SOL) muscle, resistance training
      increased the gene expression of S1P1 (P=0.000), S1P2 (P=0.603) and S1P3
      receptors (P=0.009). CONCLUSION: The key conclusion is that resistance training
      strongly caused to increase in plasma S1P content and its receptors in skeletal
      muscles of rat that might indicate to the involvement of S1P signalling in the
      molecular events controlling adaptations of resistance trained muscles which
      needs to be elucidated in future studies.

PMID- 24285108
TI  - Luteal phase support for assisted reproductive technologies: between past,
      present and future.
AB  - The luteal phase is defined as the period between ovulation and either the
      establishment of a pregnancy or the onset of menses two weeks later. Assisted
      reproductive technologies (ART), and in particular controlled ovarian stimulation
      (COS), negatively interfere with the endocrine mechanisms normally regulating the
      luteal phase. Up to now, there is no generally accepted opinion as to the most
      appropriate therapeutic schemes for luteal phase support in ART cycles.
      Progesterone-based protocols are the most frequently adopted, while alternative
      regimens including human chorionic gonadotropin (hCG) and GnRH agonists (GnRH-a)
      are controversial. A GnRH-a can be used instead of hCG for ovulation triggering
      and the effectiveness of luteal phase support in such new protocols is the object
      of a growing number of experimental studies. Currently, vaginal progesterone is
      considered as the first line therapy for luteal phase support (LPS). The starting
      time and the duration of luteal phase supplementation after the onset of
      pregnancy are still debated. Despite the lack of clinical or biological evidence
      supporting the efficacy of luteal phase support in intrauterine insemination
      cycles, the use of progesterone has become a well-established practice. 

PMID- 24285109
TI  - I spy with my little eye: typical, daily exposure to faces documented from a
      first-person infant perspective.
AB  - Exposure to faces is known to shape and change the face processing system;
      however, no study has yet documented infants' natural daily first-hand exposure
      to faces. One- and three-month-old infants' visual experience was recorded
      through head-mounted cameras. The video recordings were coded for faces to
      determine: (1) How often are infants exposed to faces? (2) To what type of faces
      are they exposed? and (3) Do frequently encountered face types reflect infants'
      typical pattern of perceptual narrowing? As hypothesized, infants spent a large
      proportion of their time (25%) exposed to faces; these faces were primarily
      female (70%), own-race (96%), and adult-age (81%). Infants were exposed to more
      individual exemplars of female, own-race, and adult-age faces than to male, other
      race, and child- or older-adult-age faces. Each exposure to own-race faces was
      longer than to other-race faces. There were no differences in exposure duration
      related to the gender or age of the face. Previous research has found that the
      face types frequently experienced by our participants are preferred over and more
      successfully recognized than other face types. The patterns of face exposure
      revealed in the current study coincide with the known trajectory of perceptual
      narrowing seen later in infancy.

PMID- 24285110
TI  - Cholesterol-enriched diet inhibits cardioprotection by ATP-sensitive K+ channel
      activators cromakalim and diazoxide.
AB  - It has been previously shown that hyperlipidemia interferes with cardioprotective
      mechanisms. Here, we investigated the interaction of hyperlipidemia with
      cardioprotection induced by pharmacological activators of ATP-sensitive K(+)
      (KATP) channels. Hearts isolated from rats fed a 2% cholesterol-enriched diet or
      normal diet for 8 wk were subjected to 30 min of global ischemia and 120 min of
      reperfusion in the presence or absence of KATP modulators. In normal diet-fed
      rats, either the nonselective KATP activator cromakalim at 10(-5) M or the
      selective mitochondrial (mito)KATP opener diazoxide at 3 * 10(-5) M significantly
      decreased infarct size compared with vehicle-treated control rats. Their
      cardioprotective effect was abolished by coadministration of the nonselective
      KATP blocker glibenclamide or the selective mitoKATP blocker 5-hydroxydecanoate,
      respectively. However, in cholesterol-fed rats, the cardioprotective effect of
      cromakalim or diazoxide was not observed. Therefore, we further investigated how
      cholesterol-enriched diet influences cardiac KATP channels. Cardiac expression of
      a KATP subunit gene (Kir6.1) was significantly downregulated in cholesterol-fed
      rats; however, protein levels of Kir6.1 and Kir6.2 were not changed. The
      cholesterol diet significantly decreased cardiac ATP, increased lactate content,
      and enhanced myocardial oxidative stress, as shown by increased cardiac
      superoxide and dityrosine formation. This is the first demonstration that
      cardioprotection by KATP channel activators is impaired in cholesterol-enriched
      diet-induced hyperlipidemia. The background mechanism may include hyperlipidemia
      induced attenuation of mitoKATP function by altered energy metabolism and
      increased oxidative stress in the heart. 

PMID- 24285111
TI  - New paradigms in inflammatory signaling in vascular endothelial cells.
AB  - Inflammation is a basic cellular process in innate and adaptive immunity.
      Vascular endothelial cells play an important role in the initiation,
      amplification, and resolution of the inflammatory response. Deregulated
      inflammatory response is implicated in a variety of cardiovascular diseases such
      as atherosclerosis, obesity, diabetes, and hypertension. Recent studies have made
      significant progresses in the understanding of the complex molecular pathways
      that mediate the pro- and anti-inflammatory signaling in endothelial cells (ECs).
      Specifically, a number of macromolecular complexes termed as signalosomes have
      been identified to integrate the proinflammatory signaling from the membrane
      receptors to key transcription factors such as nuclear factor-kappaB (NF-kappaB).
      Inflammasomes are associated with the pattern-recognition receptors such as Toll
      like receptors (TLRs), nucleotide-binding oligomerization-domain (NOD)-like
      receptors (NLRs) to mediate innate immunity responses. Emerging evidence has also
      revealed that noncoding microRNAs constitute a new class of intra- and
      intercellular signaling molecules to modulate inflammation in ECs. Thus this
      article will briefly summarize these new mechanisms with a special emphasis in
      the context of cardiovascular diseases. 

PMID- 24285112
TI  - Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold
      intolerance.
AB  - The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first
      step of mitochondrial beta-oxidation. Patients with VLCAD deficiency present with
      hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting
      and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes:
      mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and
      death. However, the contribution of different tissues to development of these
      phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient
      (cVLCAD(-/-)) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6
      mo of age, cVLCAD(-/-) mice demonstrated increased end-diastolic and end-systolic
      left ventricular dimensions and decreased fractional shortening. Surprisingly,
      selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe
      cold intolerance in mice who rapidly developed severe hypothermia, bradycardia,
      and markedly depressed cardiac function in response to fasting and cold exposure
      (+5 degrees C). We conclude that cardiac-specific VLCAD deficiency is sufficient
      to induce cold intolerance and cardiomyopathy and is associated with reduced ATP
      production. These results provide strong evidence that fatty acid oxidation in
      myocardium is essential for maintaining normal cardiac function under these
      stress conditions. 

PMID- 24285114
TI  - Cardiovascular effect of angiotensin-(1-12) in the caudal ventrolateral medullary
      depressor area of the rat.
AB  - Angiotensin (ANG)-(1-12) excites neurons via ANG II type 1 receptors (AT1Rs),
      which are present in the caudal ventrolateral medullary depressor area (CVLM). We
      hypothesized that microinjections of ANG-(1-12) into the CVLM may elicit
      decreases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve
      activity. This hypothesis was tested in urethane-anesthetized adult male Wistar
      rats. Microinjections of ANG-(1-12) into the CVLM elicited decreases in MAP, HR,
      and greater splanchnic nerve activity (GSNA). ANG-(1-12)-induced responses
      consisted of initial (first 1-8 min) and delayed (8-24 min) phases. Prior
      microinjections of losartan, A-779, and captopril into the CVLM blocked initial,
      delayed, and both phases of ANG-(1-12) responses, respectively. Blockade of GABA
      receptors in the rostral ventrolateral medullary pressor area (RVLM) attenuated
      cardiovascular responses elicited by microinjections of ANG-(1-12) into the
      ipsilateral CVLM. Microinjections of ANG-(1-12) into the CVLM potentiated the
      reflex decreases and attenuated the reflex increases in GSNA elicited by
      intravenous injections of phenylephrine and sodium nitroprusside, respectively.
      These results indicate that microinjections of ANG-(1-12) into the CVLM elicit
      decreases in MAP, HR, and GSNA. Initial and delayed phases of these responses are
      mediated via ANG II and ANG-(1-7), respectively; the effects of ANG II and ANG-(1
      7) are mediated via AT1Rs and Mas receptors, respectively. Captopril blocked both
      phases of ANG-(1-12) responses, indicating that angiotensin-converting enzyme is
      important in mediating these responses. GABA receptors in the RVLM partly mediate
      the cardiovascular responses to microinjections of ANG-(1-12) into the CVLM.
      Microinjections of ANG-(1-12) into the CVLM modulate baroreflex responses. 

PMID- 24285113
TI  - Purinergic 2X receptors play a role in evoking the exercise pressor reflex in
      rats with peripheral artery insufficiency.
AB  - Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been
      shown to play a role in evoking the exercise pressor reflex in cats. In this
      study, we attempted to extend this finding to decerebrated, unanesthetized rats
      whose femoral arteries were either freely perfused or were ligated 72 h before
      the start of the experiment. We first established that our dose of pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg), a P2X receptor
      antagonist, attenuated the pressor response to alpha,beta-methylene ATP (10
      MUg/kg), a P2X receptor agonist. We then compared the exercise pressor reflex
      before and after infusing PPADS into the arterial supply of the hindlimb muscles
      that were statically contracted. In rats with freely perfused femoral arteries,
      the peak pressor responses to contraction were not significantly attenuated by
      PPADS (before PPADS: 19 +/- 2 mmHg, 13 min after PPADS: 17 +/- 2 mmHg, and 25 min
      after PPADS: 17 +/- 3 mmHg). Likewise, the cardioaccelerator and renal
      sympathetic nerve responses were not significantly attenuated. In contrast, we
      found that in rats whose femoral arteries were ligated PPADS significantly
      attenuated the peak pressor responses to contraction (before PPADS: 37 +/- 5
      mmHg, 13 min after PPADS: 27 +/- 6 mmHg, and 25 min after PPADS: 25 +/- 5 mmHg; P
      < 0.05). Heart rate was not significantly attenuated, but renal SNA was at
      certain time points over the 30-s contraction period. We conclude that P2X
      receptors play a substantial role in evoking the exercise pressor reflex in rats
      whose femoral arteries were ligated but play only a minimal role in evoking the
      reflex in rats whose femoral arteries were freely perfused. 

PMID- 24285115
TI  - Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1
      shedding.
AB  - Endothelial cells (ECs) are covered by a surface glycocalyx layer that forms part
      of the barrier and mechanosensing functions of the blood-tissue interface.
      Removal of albumin in bathing media induces collapse or shedding of the
      glycocalyx. The electrostatic interaction between arginine residues on albumin,
      and negatively charged glycosaminoglycans (GAGs) in the glycocalyx have been
      hypothesized to stabilize the glycocalyx structure. Because albumin is one of the
      primary carriers of the phospholipid sphingosine-1-phosphate (S1P), we evaluated
      the alternate hypothesis that S1P, acting via S1P1 receptors, plays the primary
      role in stabilizing the endothelial glycocalyx. Using confocal microscopy on rat
      fat-pad ECs, we demonstrated that heparan sulfate (HS), chondroitin sulfate (CS),
      and ectodomain of syndecan-1 were shed from the endothelial cell surface after
      removal of plasma protein but were retained in the presence of S1P at
      concentrations of >100 nM. S1P1 receptor antagonism abolished the protection of
      the glycocalyx by S1P and plasma proteins. S1P reduced GAGs released after
      removal of plasma protein. The mechanism of protection from loss of glycocalyx
      components by S1P-dependent pathways was shown to be suppression of
      metalloproteinase (MMP) activity. General inhibition of MMPs protected against
      loss of CS and syndecan-1. Specific inhibition of MMP-9 and MMP-13 protected
      against CS loss. We conclude that S1P plays a critical role in protecting the
      glycocalyx via S1P1 and inhibits the protease activity-dependent shedding of CS,
      HS, and the syndecan-1 ectodomain. Our results provide new insight into the role
      for S1P in protecting the glycocalyx and maintaining vascular homeostasis. 

PMID- 24285118
TI  - Generalised acanthosis nigricans in childhood with short stature associated with
      poor response to growth hormone provocation.

PMID- 24285117
TI  - Possible involvement of HSP90-HSF1 multichaperone complex in impairment of HSP72
      induction in the failing heart following myocardial infarction in rats.
AB  - It is generally accepted that an increase in the myocardial level of heat-shock
      protein 72 (HSP72) protects viable cardiac tissue against myocardial infarction
      (MI)-induced stress. However, the induction of HSP72 after exposure to heat shock
      (HS) is blunted in the failing rat heart following MI. The mechanisms underlying
      this impairment in the HSP72 induction ability of the failing heart are not yet
      clearly defined. In the present study, we examined the involvement in heat-shock
      factor 1 (HSF1), a transcription factor of HSPs, in decreased ability for HSP72
      induction in the failing rat heart following MI. In the failing heart, nuclear
      translocation of the HSF1 after exposure to hyperthermia was markedly reduced,
      whereas HSF1 in the cytosolic fraction and the HSP90 chaperone complex containing
      HSF1, a repressor of HSF1, were increased. Treatment with an HSP90 inhibitor, 17
      allylamino-17-demethoxygel-danamycin, appeared to dissociate the interaction of
      HSF1 with HSP90, and then induced HSP72 in the failing heart after exposure to
      hyperthermia. These results suggest that an increase in the multichaperone
      complex, especially the HSF1-HSP90 interaction, associated with attenuation of
      HSF1 translocation into the nucleus, was involved in the impairment of HS-induced
      HSP72 induction in the failing heart following MI. 

PMID- 24285119
TI  - Facile synthesis of mononuclear early transition-metal complexes of kappa3cyclo
      tetrametaphosphate ([P4O12]4-) and cyclo-trimetaphosphate ([P3O9]3-.
AB  - We herein report the preparation of several mononuclear-metaphosphate complexes
      using simple techniques and mild conditions with yields ranging from 56% to 78%.
      Treatment of cyclo-tetrametaphosphate ([TBA]4[P4O12].5H2O, TBA = tetra-n
      butylammonium) with various metal sources including (CH3CN)3Mo(CO)3,
      (CH3CN)2Mo(CO)2(eta(3)-C3H5)Cl, MoO2Cl2(OSMe2)2, and VOF3, leads to the clean and
      rapid formation of [TBA]4[(P4O12)Mo(CO)3].2H2O, [TBA]3[(P4O12)Mo(CO)2(eta(3)
      C3H5)], [TBA]3[(P4O12)MoO2Cl] and [TBA]3[(P4O12)VOF2].Et2O salts in isolated
      yields of 69, 56, 68, and 56% respectively. NMR spectroscopy, NMR simulations and
      single crystal X-ray studies reveal that the [P4O12](4-) anion behaves as a
      tridentate ligand wherein one of the metaphosphate groups is not directly bound
      to the metal. cyclo-Trimetaphosphate-metal complexes were prepared using a
      similar procedure i.e., treatment of [PPN]3[P3O9].H2O (PPN =
      bis(triphenylphosphine)iminium) with the metal sources (CH3CN)2Mo(CO)2(eta(3)
      C3H5)Cl, MoO2Cl2(OSMe2)2, MoOCl3, VOF3, WOCl4, and WO2Cl2(CH3CN)2 to produce the
      corresponding salts, [PPN]2[(P3O9)Mo(CO)2(eta(3)-C3H5)], [PPN]2[(P3O9)MoO2Cl],
      [PPN]2[(P3O9)MoOCl2], [PPN]2[(P3O9)VOF2].2CH2Cl2, and [PPN]2[(P3O9)WO2Cl] in
      isolated yields of 78, 56, 75, 59, and 77% respectively. NMR spectroscopy, NMR
      simulations and single-crystal X-ray studies indicate that the trianionic ligand
      [P3O9](3-) in these complexes also has kappa(3) connectivity. 

PMID- 24285116
TI  - Epoxyeicosatrienoic acids pretreatment improves amyloid beta-induced
      mitochondrial dysfunction in cultured rat hippocampal astrocytes.
AB  - Amyloid-beta (Abeta) has long been implicated as a causative protein in
      Alzheimer's disease. Cellular Abeta accumulation is toxic and causes
      mitochondrial dysfunction, which precedes clinical symptoms of Alzheimer's
      disease pathology. In the present study, we explored the possible use of
      epoxyeicosatrienoic acids (EETs), epoxide metabolites of arachidonic acid, as
      therapeutic target against Abeta-induced mitochondrial impairment using cultured
      neonatal hippocampal astrocytes. Inhibition of endogenous EET production by a
      selective epoxygenase inhibitor, MS-PPOH, caused a greater reduction in
      mitochondrial membrane potential in the presence of Abeta (1, 10 MUM) exposure
      versus absence of Abeta. MS-PPOH preincubation also aggravated Abeta-induced
      mitochondrial fragmentation. Preincubation of the cells with either 14,15- or
      11,12-EET prevented this mitochondrial depolarization and fragmentation. EET
      pretreatment also further improved the reduction observed in mitochondrial oxygen
      consumption in the presence of Abeta. Preincubation of the cells with EETs
      significantly improved cellular respiration under basal condition and in the
      presence of the protonophore, carbonyl cyanide 4-(trifluoromethoxy)
      phenylhydrazone (FCCP). The uncoupling of ATP synthase from the electron transfer
      chain that occurred in Abeta-treated cells was also prevented by preincubation
      with EETs. Lastly, cellular reactive oxygen species production, a hallmark of
      Abeta toxicity, also showed significant reduction in the presence of EETs. We
      have previously shown that Abeta reduces EET synthesis in rat brain homogenates
      and cultured hippocampal astrocytes and neurons (Sarkar P, Narayanan J, Harder
      DR. Differential effect of amyloid beta on the cytochrome P450 epoxygenase
      activity in rat brain. Neuroscience 194: 241-249, 2011). We conclude that
      reduction of endogenous EETs may be one of the mechanisms through which Abeta
      inflicts toxicity and thus supplementing the cells with exogenous EETs improves
      mitochondrial dynamics and prevents metabolic impairment. 

PMID- 24285121
TI  - Disbalance between mortality and non-fatal vascular events in the CHAMPION
      PHOENIX trial: the cangrelor efficacy challenge.
AB  - The recently published, largest trial with cangrelor, the Cangrelor versus
      Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION)
      PHOENIX, suggested that the experimental agent significantly reduced the rate of
      stent thrombosis (ST) and myocardial infarction (MI) during PCI at 48 hours (h)
      and 30 days. However, the declared impressive cangrelor vascular non-fatal
      benefit was contradicted by identical deaths at 48 h, and a trend toward excess
      mortality at 30 days. We analysed the mismatch between outcomes in the CHAMPION
      PHOENIX trial. The trial reported identical mortality (18 death in each arm; odds
      ratio [OR] 1.00 (0.52-1.92); p>0.999) at 48 h, but more deaths, 60 vs 55, after
      cangrelor at 30 days. There was a significant reduction of ST from 0.8% (n=46) of
      the patients in the cangrelor group versus 1.4% (n=74) in the clopidogrel group
      (odds ratio, 0.62; 95% CI, 0.43 to 0.90; p= 0.01) at 48 h, and a persistent but
      less impressive ST prevention benefit OR of 0.68 (0.50=0.92, p = 0.01) at 30
      days. There were also 48 less MI's following cangrelor usage enforced by a
      significant difference (odds ratio 0.80 (0.67-0.97) p = 0.02), which was also
      less prevalent at 30 days (OR 0.82 (0.68-0.98), p = 0.03). The reported ST/MI
      advantage should result in at least a trend towards numerically less deaths after
      cangrelor at 30 days follow-up, which was opposite of the results reported in
      CHAMPION-PHOENIX trial. Efficacy of cangrelor is challenged by the
      disproportional "reduction" of ST and MI conflicting with identical mortality at
      48 h and worsened at day 30 fatalities. The dissociation between vascular
      mortality and non-fatal vascular ischaemic occlusions, unless compensated by some
      other unreported cause(s) of death, should be explored and explained.
      Unadjudicated 30-day outcomes, and all ST types should be fully disclosed. The
      ongoing FDA cangrelor review should focus on appropriate event count and/or
      possible mismatch between site-reported and extra adjudicated events in the
      CHAMPION-PHOENIX trial. 

PMID- 24285122
TI  - Prospective randomized comparison between axial- and lateral-viewing capsule
      endoscopy systems in patients with obscure digestive bleeding.
AB  - BACKGROUND AND STUDY AIM: Video capsule endoscopy (VCE) is recommended as the
      first exploration in obscure digestive bleeding. The efficiency of the PillCam
      SB2 (Given Imaging) has been widely reported. The CapsoCam capsule (Capsovision)
      has four cameras allowing the exploration of the small bowel through 360 degrees 
      lateral viewing. This system does not include a recording system so the capsule
      has to be retrieved by the patient after expulsion in order for the film to be
      downloaded. The aim of this study was to evaluate diagnostic concordance (kappa
      value) of the PillCam SB2 and CapsoCam capsules in the same patients. METHODS:
      This was a prospective comparative study in four French referral endoscopy units.
      Consecutive patients ingested the two capsules 1 hour apart and in a randomized
      order. RESULTS: In the 73 included patients there were 13 technical issues (11
      CapsoCam, 2 PillCam SB2). Of the 60 patients with analyzable data, and following
      expert review of all discordant cases, a concordant positive diagnosis was
      obtained in 23 (38.3 %) and a negative diagnosis was obtained and 26 patients
      (43.3 %). Concordance was good, with a kappa value of 0.63 in analyzable
      patients, and 46.7 % diagnosis with CapsoCam vs. 48.3 % with PillCam SB2.
      CapsoCam and PillCam SB2 procedures identified 81.8 % (27 /33) and 84.8 % (28
      /33) of positive patients, respectively (P = 0.791). In a per lesion analysis,
      the CapsoCam capsule detected significantly more lesions (108 vs. 85 lesions; P =
      0.001). Reading time was longer for CapsoCam procedures (32.0 vs. 26.2 minutes; P
      = 0.002). CONCLUSION: This study shows comparable efficiency of the CapsoCam and
      PillCam SB2 capsule systems in terms of diagnostic yield and image quality.

PMID- 24285123
TI  - Pseudo-buried Barrett's post radiofrequency ablation for Barrett's esophagus,
      with or without prior endoscopic resection.
AB  - BACKGROUND AND STUDY AIM: In our experience, biopsies from small residual islands
      of nonburied Barrett's mucosa after radiofrequency ablation (RFA) are
      occasionally reported by pathologists to contain "buried Barrett's" upon
      histological evaluation, despite the fact that these islands of columnar mucosa
      were visible endoscopically. The aim of this study was to evaluate the frequency
      of buried Barrett's in biopsies obtained from small residual Barrett's islands (
      < 5 mm) sampled post-RFA, compared with biopsies from normal neosquamous
      epithelium. PATIENTS AND METHODS: Biopsies obtained from normal-appearing
      neosquamous epithelium and from small Barrett's islands ( < 5 mm) in 69
      consecutive Barrett's patients treated with RFA were evaluated for the presence
      of buried columnar mucosa. RESULTS: A total of 2515 biopsies were obtained from
      neosquamous epithelium during follow-up post-RFA. Buried glands were found in 0.1
      % of biopsies from endoscopically normal neosquamous epithelium. However, when
      small islands of columnar mucosa were biopsied, buried glands were detected in 21
      % of biopsies. CONCLUSION: To avoid accidental sampling of small islands
      resulting in a false-positive histological diagnosis of buried Barrett's,
      thorough inspection should be performed before obtaining biopsies during post-RFA
      follow-up.

PMID- 24285124
TI  - Visual and refractive outcomes of laser cataract surgery.
AB  - PURPOSE OF REVIEW: Femtosecond laser is a promising new technology for the field
      of cataract surgery. Early studies have investigated many factors including
      visual outcomes, complication rates, and financial overhead costs. This review
      analyzes the most recent clinical studies of visual and refractive outcomes in
      laser cataract surgery, including those that make comparisons to outcomes found
      in conventional phacoemulsification cataract surgery. RECENT FINDINGS: As
      femtosecond laser cataract surgery has only emerged recently, there is limited
      literature available regarding visual outcomes. Most but not all existing studies
      showed no statistically significant difference in visual acuity and mean absolute
      refractive error between laser and conventional cataract surgery cases. SUMMARY:
      The majority of studies examined found visual acuity or refractive outcomes of
      femtosecond laser to be statistically equivalent to those of conventional
      phacoemulsification cataract surgery. However, the learning curve involved with
      laser use may account for these early results, which could potentially improve as
      better technology and surgical techniques are developed. Further long-term
      outcomes studies are necessary to more accurately evaluate the benefits and
      drawbacks of femtosecond laser cataract surgery.

PMID- 24285125
TI  - Anti-inflammatory and analgesic effects of methanol extract and fractions of
      Acalypha wilkesiana leaves.
AB  - BACKGROUND: This study was carried out to evaluate the anti-inflammatory and the
      analgesic potentials of Acalypha wilkesiana leaf extract in experimental animals.
      METHODS: The anti-inflammatory potential was investigated using an acute rat
      model. Aspirin at 150 mg/kg, indomethacin at 10 mg/kg as positive control, and
      methanolic extracts and solvent fractions of A. wilkesiana at doses of 400 and
      200 mg/kg, respectively, were administered orally to rats and compared with a
      negative control group given 10 mL/kg Tween 80. At an A. wilkesiana dose of 400
      mg/kg body weight, the analgesic effect was also studied using the hot plate
      method and the acetic acid-induced writhing model in mice. RESULTS: Percentage
      inhibition of the paw volume was highest in rats administered indomethacin
      (85.7%) followed by the group administered methanolic extract of A. wilkesiana
      (74.1%), whereas the group given aspirin had 65.5% inhibition of edema and the
      group given a 200 mg/kg dose of chloroform fraction of A. wilkesiana had 93%
      inhibition of increase in paw volume, a value higher than the performance of the
      standard drugs indomethacin (85%) and aspirin (68%). Also, the extract caused an
      increase in the reaction time in the hot plate test and in the acetic acid test.
      The mean number of writhings was significantly reduced in the group of mice
      administered 400 mg/kg extract of A. wilkesiana leaves (25.8+/-1.3) when compared
      with the control (46.7+/-1.4) but higher than the group of mice administered the
      standard analgesic agent paracetamol (23.5+/-1.3). CONCLUSIONS: This study
      suggested that A. wilkesiana leaves have anti-inflammatory and analgesic
      potential comparable with those of standard drugs.

PMID- 24285126
TI  - Virgin coconut oil protects against liver damage in albino rats challenged with
      the anti-folate combination, trimethoprim-sulfamethoxazole.
AB  - BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad-spectrum
      antibiotic. However, its use is associated with toxic reactions. Virgin coconut
      oil (VCO), derived from coconut, has been widely used throughout history for its
      medicinal value. The aim of this study was to investigate the beneficial actions
      of VCO against TMP-SMX-induced alterations in serum biochemical end points.
      METHODS: Twenty rats were divided into four groups. Group 1 (control) received no
      drug, whereas group 2 received TMP-SMX (8/40 mg/kg) twice daily for 7 days. Group
      3 was administered coconut oil at a dose of 600 mg/kg body weight per day. The
      last group was treated with TMP-SMX (8/40 mg/kg) and coconut oil (600 mg/kg)
      simultaneously. Blood samples were collected from all groups on the 8th day of
      the experiment for measurement of serum biochemical parameters. Organ weights and
      coefficients were also evaluated. RESULTS: TMP-SMX caused a significant (p<0.05)
      increase in the levels of serum total bilirubin, lactate dehydrogenase, and
      alkaline phosphatase by 192%, 67%, and 41%, respectively, relative to controls.
      This was followed by a significant reduction in triglyceride and relative kidney
      weight by 40% and 7%, respectively. There were no significant differences
      (p>0.05) in the activities of serum aminotransferases, total acid phosphatase,
      gamma-glutamyl transferase, uric acid, cholesterol, albumin, and urea levels.
      Supplementation of VCO ameliorated TMP-SMX-induced effects by restoring the
      levels of total bilirubin, alkaline phospahatase, and lactate dehydrogenase.
      CONCLUSIONS: The results of this study demonstrate that the active components of
      coconut oil had protective effects against the toxic effects induced by TMP-SMX
      administration, especially in the liver of rats.

PMID- 24285127
TI  - Rapid extraction, identification and quantification of drugs of abuse in hair by
      immunoassay and ultra-performance liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: Drug testing in hair is a unique analysis in pharmacotoxicology for
      establishing a past repeated history of consumption or passive exposure to
      psychotropic substances. A rather lengthy sample treatment is usually required
      before parent drugs and eventual metabolites are amenable to quali-quantitative
      analysis. METHODS: We evaluated a high throughput screening and confirmation
      analysis of drugs of abuse in hair by immunoassay and a validated ultra
      performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after
      applying a rapid digestion of the keratin matrix with VMA-T reagent before
      screening assay and M3 reagent before confirmatory analysis. RESULTS: Samples
      digestion with VMA-T reagent and immunometric screening analysis of hair
      calibrators, controls and clinical samples for a total of 150 samples was
      completed in 4 h. No false-positive and -negative results were found for the
      control material. UPLC-MS/MS analysis confirmed all of the 31 adult hair samples
      positive to the screening test using internationally established cut-offs, and
      identified and quantified drugs of abuse in 32 pediatric hair samples, applying
      lower limits of quantification from 0.01 to 0.1 ng analyte per mg hair.
      Analytical recovery was between 70.9% and 100.7%. Intra- and inter-assay
      imprecision and inaccuracy were always lower than 10%. CONCLUSIONS: Rapid
      extraction, identification and quantification of drugs of abuse in hair by
      immunoassay and UPLC-MS/MS was tested for its feasibility in clinical samples and
      provided excellent results for rapid and effective drug testing in hair in
      epidemiological studies.

PMID- 24285128
TI  - Renal function after percutaneous coronary interventions depending on the type of
      hydration.
AB  - PURPOSE: The aim of our study was to evaluate renal function assessed by serum
      creatinine as well as novel biomarkers in 142 patients with stable coronary heart
      disease and normal serum creatinine undergoing percutaneous coronary
      interventions (PCI) depending on the type of hydration: physiological saline vs.
      sodium bicarbonate (1:1 randomization). MATERIALS AND METHODS: Serum and urinary
      NGAL were evaluated before and after 8-12, and 24 hours after PCI. Serum cystatin
      C, serum creatinine, estimated glomerular filtration rate using different
      formulae were assessed before PCI, and 24 hours after the procedure. RESULTS:
      Only 2 patients (2.8%) from the saline-hydrated group fulfilled the criteria for
      CI-AKI. In patients hydrated with sodium bicarbonate serum creatinine declined
      significantly (p<0.01). In patients hydrated with sodium bicarbonate a
      significant fall in serum NGAL after 8-12 hours was found. In sodium bicarbonate
      group cystatin C decreased non significantly after 8-12 hours, then returned to
      the baseline values. In patients hydrated with physiological saline serum NGAL
      before PCI and after 24 hours correlated positively with cystatin C and eGFR by
      CKD-EPI. In patients hydrated with sodium bicarbonate baseline serum NGAL
      correlated with NGAL baseline cystatin C and eGFR by CKD-EPI, similarly serum
      NGAL after 24 hours correlated with cystatin C. CONCLUSION: We suggest to rather
      use sodium bicarbonate in a hydration protocol in patients undergoing PCI.
      However, the value of NGAL in this setting remains to be elucidated and volume
      expansion remain the unquestionable prevention methods of CI-AKI.

PMID- 24285129
TI  - How to estimate overweight in pubescent asthmatics?
AB  - PURPOSE: The purpose of our research was to compare the body mass index (BMI) and
      selected anthropometric parameters in asthmatic and non-asthmatic pubescents.
      MATERIAL AND METHODS: The study group consisted of 64 asthmatic boys and 45
      girls; the control group consisted of 68 nonasthmatic boys and 48 non-asthmatic
      girls. All the children were 12-14 years old. We measured anthropometric
      parameters by a standardized method and the percentage of fat using the simple 2
      site skinfold method. Additionally, we calculated the percentage of body
      composition (Matiegka) and the components of somatotype (Heath-Carter).
      Statistical significance was estimated at the level of p<0.05 by ANOVA test.
      RESULTS: The asthmatic boys were significantly shorter than the non-asthmatic
      (p=0.015), however, we did not find any significant differences in weight and/or
      BMI in boys nor girls. The asthmatic boys had significantly higher fat mass %
      than the non-asthmatic ones (p<0.001). Moreover, they had significantly lower
      muscle mass % (p<0.001) as well as the bone mass % (p<0.001). The asthmatic girls
      had higher fat mass % than the non-asthmatic ones (p=0.028) and lower muscle mass
      % (p<0.001). The simple 2-site skinfold method also showed higher fat % in the
      asthmatic boys (p<0.001) but not in the girls. Examining the Heath-Carter
      somatotype components, the higher endomorphy was the only significant difference
      in asthmatic boys (p<0.001) and near significant in asthmatic girls (p=0.053).
      CONCLUSION: Examination of the BMI alone is not sufficient in asthmatic children
      because of their high percentage of fat. That is why additionally testing fat %
      is recommended.

PMID- 24285130
TI  - Second order optimization for the inference of gene regulatory pathways.
AB  - With the increasing availability of experimental data on gene interactions,
      modeling of gene regulatory pathways has gained special attention. Gradient
      descent algorithms have been widely used for regression and classification
      applications. Unfortunately, results obtained after training a model by gradient
      descent are often highly variable. In this paper, we present a new second order
      learning rule based on the Newton's method for inferring optimal gene regulatory
      pathways. Unlike the gradient descent method, the proposed optimization rule is
      independent of the learning parameter. The flow vectors are estimated based on
      biomass conservation. A set of constraints is formulated incorporating weighting
      coefficients. The method calculates the maximal expression of the target gene
      starting from a given initial gene through these weighting coefficients. Our
      algorithm has been benchmarked and validated on certain types of functions and on
      some gene regulatory networks, gathered from literature. The proposed method has
      been found to perform better than the gradient descent learning. Extensive
      performance comparison with the extreme pathway analysis method has underlined
      the effectiveness of our proposed methodology.

PMID- 24285131
TI  - Hepatocyte levels of CD73 contribute to Mallory-Denk body formation.

PMID- 24285132
TI  - Biopsy techniques: shave, punch, or excision?

PMID- 24285133
TI  - Preliminary studies of a novel cyclopentadienyl tricarbonyl technetium-99m fatty
      acid derivative for myocardical imaging.
AB  - This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl
      tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was
      prepared with 26.5 +/- 4.3% of radiochemical yield and more than 98% of
      radiochemical purity. Tissue distribution in mice showed that high radioactivity
      accumulated in the heart with moderate clearance. However, unfortunately, similar
      to those of other technetium-labeled fatty acid analogs, the biodistribution
      studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1
      cannot be used as myocardial imaging agent, and it may provide a theoretical
      basis or a lab experience for corresponding fatty acid tracers studies. 

PMID- 24285134
TI  - Chirally deuterated benzyl chlorides from benzyl alcohols via
      hexachloroacetone/polymer-supported triphenylphosphine: synthesis of protected
      (2S, 3S)-[3-(2)H, (15)N]-tyrosine.
AB  - Chirally deuterated benzyl chlorides were prepared using novel, general
      hexachloroacetone/polymer-supported triphenylphosphine treatment of chirally
      deuterated benzyl alcohols. Doubly labeled protected tyrosine was obtained in 62%
      yield with 86% de at the alpha-carbon and 82% de at the beta-carbon. Key in the
      synthesis was the alkylation of (15)N-labeled (-)-8-phenylmenthylhippurate with R
      (-)-4-triisopropylsilyloxybenzyl-alpha-d chloride.

PMID- 24285135
TI  - Iodine-131 radiolabeling of poly ethylene glycol-coated gold nanorods for in vivo
      imaging.
AB  - Gold nanorods (GNRs) can be used in various biomedical applications; however,
      very little is known about their in vivo tissue distribution by radiolabeling.
      Here, we have developed a rapid and simple method with high yield and without
      disturbing their optical properties for radiolabeling of gold rods with iodine
      131 in order to track in vivo tissue uptake of GNRs after systemic administration
      by biodistribution analysis and gamma-imaging. Following intravenous injection
      into rat, PEGylated GNRs have much longer blood circulation times. 

PMID- 24285136
TI  - A modern approach to the synthesis of 2-(4-chlorophenyl)[2-(14)C]thiazol-4
      ylacetic acid ([(14)C] fenclozic acid) and its acyl glucuronide metabolite.
AB  - An updated approach to the 1960s synthesis of [(14)C] fenclozic acid from
      labelled potassium cyanide is presented. By employing modern synthetic
      methodology and purification techniques, many of the inherent hazards in the
      original synthesis are avoided or significantly reduced. The concomitant labelled
      stereoselective synthesis of the key acyl glucuronide metabolite (the 1-beta-O
      acyl glucuronide) is also described.

PMID- 24285137
TI  - Expeditious syntheses of stable and radioactive isotope-labeled anticonvulsant
      agent, JNJ-26990990, and its metabolites.
AB  - Syntheses of stable and radioactive isotope-labeled anticonvulsant agent, JNJ
      26990990, that is, N-(benzo[b]thien-3-ylmethyl)-sulfamide and its metabolites are
      described. [(13)C(15)N]Benzo[b]thiophene-3-carbonitrile was first prepared by
      coupling of 3-bromo-benzo[b]thiophene with [(13)C(15)N]-copper cyanide. The
      resultant [(13)C(15)N]benzo[b]thiophene-3-carbonitrile was reduced with lithium
      aluminum deuteride to give [(13)CD2(15)N]benzo[b]thiophen-3-yl-methylamine; which
      was then coupled with sulfamide to afford [(13)CD2(15)N]-N-(benzo[b]thien-3
      ylmethyl)-sulfamide, the stable isotope-labeled compound with four stable isotope
      atoms. Direct oxidation of [(13)CD2(15)N]-N-(benzo[b]thien-3-ylmethyl)-sulfamide
      with hydrogen peroxide and peracetic acid gave the stable isotope-labeled
      sulfoxide and sulfone metabolites. On the other hand, radioactive (14)C-labeled N
      (benzo[b]thien-3-ylmethyl)-sulfamide was prepared conveniently by sequential
      coupling of 3-bromo-benzo[b]thiophene with [(14)C]-copper cyanide, reduction of
      the carbonitrile to carboxaldehyde, and reductive amination with sulfamide.

PMID- 24285138
TI  - Gram-scale synthesis and efficient purification of 13C-labeled levoglucosan from
      13C glucose.
AB  - (13)C-Labeled levoglucosan has been synthesized and purified in good yield, and
      on the gram scale in one step from commercially available (13)C glucose. This one
      step protocol uses 2-chloro-1,3-dimethylimidazolinium chloride that serves to
      selectively activate the anomeric carbon toward substitution reactions. The
      labeled glucose is then smoothly converted to the anhydroglucose. Purification is
      efficiently achieved on large scale by chromatography on silica gel.

PMID- 24285146
TI  - Isolation and characterization of a heavy metal-resistant, thermophilic esterase
      from a Red Sea brine pool.
AB  - The Red Sea Atlantis II brine pool is an extreme environment that displays
      multiple harsh conditions such as high temperature, high salinity and high
      concentrations of multiple, toxic heavy metals. The survival of microbes in such
      an environment by utilizing resistant enzymes makes them an excellent source of
      extremophilic enzymes. We constructed a fosmid metagenomic library using DNA
      isolated from the deepest and most secluded layer of this pool. We report the
      isolation and biochemical characterization of an unusual esterase: EstATII.
      EstATII is thermophilic (optimum temperature, 65 degrees C), halotolerant
      (maintains its activity in up to 4.5 M NaCl) and maintains at least 60% of its
      activity in the presence of a wide spectrum of heavy metals. The combination of
      biochemical characteristics of the Red Sea Atlantis II brine pool esterase, i.e.,
      halotolerance, thermophilicity and resistance to heavy metals, makes it a
      potentially useful biocatalyst. 

PMID- 24285147
TI  - Selective ion-induced intermixing and damage in low-dimensional GaN/AlN quantum
      structures.
AB  - Ion-induced intermixing and damage is evaluated in GaN/AlN superlattices of
      quantum dots (QDs) and quantum wells (QWs) using 100 keV Ar(+) implantation at
      low temperature (15 K). Despite the similar damage build up at low fluences, a
      significant increase of the damage accumulation takes place for QDs at high
      fluences. Elemental depth profiles were fitted with a diffusion model, revealing
      the higher intermixing efficiency in QD superlattices, significantly higher than
      for QWs. The scaling of diffusion length with the local fluence and defect
      concentration is understood on the basis of cascade mixing and migration of
      defects in the cation sublattice. The selective intermixing/damage of QDs is
      explained by the promotion of lateral diffusion mechanisms that result in smooth
      interfaces, as well as by an enhanced diffusivity due to the characteristic
      strain distribution in QD superlattices.

PMID- 24285148
TI  - Respiratory motor outputs following unilateral midcervical spinal cord injury in
      the adult rat.
AB  - The present study was designed to investigate the impact of midcervical spinal
      cord injury on respiratory outputs and compare respiratory recovery following
      high- vs. midcervical spinal injury. A unilateral hemisection (Hx) in the spinal
      cord at C2 or C4 was performed in adult rats. Respiratory behaviors of
      unanesthetized animals were measured at normoxic baseline and hypercapnia by
      whole body plethysmography at 1 day and 1, 2, 4, and 8 wk after spinal injury.
      C2Hx and C4Hx induced a similar rapid shallow breathing pattern at 1 day
      postinjury. The respiratory frequency of C4Hx animals gradually returned to
      normal, but the tidal volume from 1 to 8 wk postinjury remained lower than that
      of the control animals. Linear regression analyses indicated that the tidal
      volume recovery was greater in the C4Hx animals than in the C2Hx animals at the
      baseline, but not at hypercapnia. The bilateral phrenic nerve activity was
      recorded in anesthetized animals under different respiratory drives at 8-9 wk
      postinjury. The phrenic burst amplitude ipsilateral to the lesion reduced
      following both high- and midcervical Hx; however, the ability to increase
      activity was lower in the C4Hx animals than in the C2Hx animals. When the data
      were normalized by the maximal inspiratory effort during asphyxia, the phrenic
      burst amplitude enhanced in the C4Hx animals, but reduced in the C2Hx animals
      compared with the control animals. These results suggest that respiratory
      deficits are evident following midcervical Hx, and that respiratory recovery and
      neuroplasticity of phrenic outputs are different following high- vs. midcervical
      spinal injury. 

PMID- 24285150
TI  - Muscle carnosine loading by beta-alanine supplementation is more pronounced in
      trained vs. untrained muscles.
AB  - Carnosine occurs in high concentrations in human skeletal muscle and assists
      working capacity during high-intensity exercise. Chronic beta-alanine (BA)
      supplementation has consistently been shown to augment muscle carnosine
      concentration, but the effect of training on the carnosine loading efficiency is
      poorly understood. The aim of the present study was to compare muscle carnosine
      loading between trained and untrained arm and leg muscles. In a first study (n =
      17), reliability of carnosine quantification by proton magnetic resonance
      spectroscopy ((1)H-MRS) was evaluated in deltoid and triceps brachii muscles. In
      a second study, participants (n = 35; 10 nonathletes, 10 cyclists, 10 swimmers,
      and 5 kayakers) were supplemented with 6.4 g/day of slow-release BA for 23 days.
      Carnosine content was evaluated in soleus, gastrocnemius medialis, and deltoid
      muscles by (1)H-MRS. All the results are reported as arbitrary units. In the
      nonathletes, BA supplementation increased carnosine content by 47% in the arm and
      33% in the leg muscles (not significant). In kayakers, the increase was more
      pronounced in arm (deltoid) vs. leg (soleus + gastrocnemius) muscles (0.089 vs.
      0.049), whereas the reverse pattern was observed in cyclists (0.065 vs. 0.084).
      Swimmers had significantly higher increase in carnosine in both deltoid (0.107
      vs. 0.065) and gastrocnemius muscle (0.082 vs. 0.051) compared with nonathletes.
      We showed that 1) carnosine content can be reliably measured by (1)H-MRS in
      deltoid muscle, 2) carnosine loading is equally effective in arm vs. leg muscles
      of nonathletes, and 3) carnosine loading is more pronounced in trained vs.
      untrained muscles.

PMID- 24285149
TI  - Effects of oral glutamine supplementation on exercise-induced gastrointestinal
      permeability and tight junction protein expression.
AB  - The objectives of this study are threefold: 1) to assess whether 7 days of oral
      glutamine (GLN) supplementation reduces exercise-induced intestinal permeability;
      2) whether supplementation prevents the proinflammatory response; and 3) whether
      these changes are associated with upregulation of the heat shock response. On
      separate occasions, eight human subjects participated in baseline testing and in
      GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run.
      Intestinal permeability was higher in the PLA trial compared with baseline and
      GLN trials (0.0604 +/- 0.047 vs. 0.0218 +/- 0.008 and 0.0272 +/- 0.007,
      respectively; P < 0.05). IkappaBalpha expression in peripheral blood mononuclear
      cells was higher 240 min after exercise in the GLN trial compared with the PLA
      trial (1.411 +/- 0.523 vs. 0.9839 +/- 0.343, respectively; P < 0.05). In vitro
      using the intestinal epithelial cell line Caco-2, we measured effects of GLN
      supplementation (0, 4, and 6 mM) on heat-induced (37 degrees  or 41.8 degrees C)
      heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin
      expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41
      degrees C compared with 0 mM at 41 degrees C (1.785 +/- 0.495 vs. 0.6681 +/-
      0.290, and 1.973 +/- 0.325 vs. 1.133 +/- 0.129, respectively; P < 0.05). Occludin
      levels increased after 4 mM supplementation at 41 degrees C and 6 mM at 41
      degrees C compared with 0 mM at 41 degrees C (1.236 +/- 0.219 and 1.849 +/- 0.564
      vs. 0.7434 +/- 0.027, respectively; P < 0.001). GLN supplementation prevented
      exercise-induced permeability, possibly through HSF-1 activation.

PMID- 24285155
TI  - [The EGD -- strength for the weak -- yesterday, today and in the future?].

PMID- 24285151
TI  - Automatically annotating topics in transcripts of patient-provider interactions
      via machine learning.
AB  - BACKGROUND: Annotated patient-provider encounters can provide important insights
      into clinical communication, ultimately suggesting how it might be improved to
      effect better health outcomes. But annotating outpatient transcripts with Roter
      or General Medical Interaction Analysis System (GMIAS) codes is expensive,
      limiting the scope of such analyses. We propose automatically annotating
      transcripts of patient-provider interactions with topic codes via machine
      learning. METHODS: We use a conditional random field (CRF) to model utterance
      topic probabilities. The model accounts for the sequential structure of
      conversations and the words comprising utterances. We assess predictive
      performance via 10-fold cross-validation over GMIAS-annotated transcripts of 360
      outpatient visits (>230,000 utterances). We then use automated in place of manual
      annotations to reproduce an analysis of 116 additional visits from a randomized
      trial that used GMIAS to assess the efficacy of an intervention aimed at
      improving communication around antiretroviral (ARV) adherence. RESULTS: With
      respect to 6 topic codes, the CRF achieved a mean pairwise kappa compared with
      human annotators of 0.49 (range: 0.47-0.53) and a mean overall accuracy of 0.64
      (range: 0.62-0.66). With respect to the RCT reanalysis, results using automated
      annotations agreed with those obtained using manual ones. According to the manual
      annotations, the median number of ARV-related utterances without and with the
      intervention was 49.5 versus 76, respectively (paired sign test P = 0.07). When
      automated annotations were used, the respective numbers were 39 versus 55 (P =
      0.04). While moderately accurate, the predicted annotations are far from perfect.
      Conversational topics are intermediate outcomes, and their utility is still being
      researched. CONCLUSIONS: This foray into automated topic inference suggests that
      machine learning methods can classify utterances comprising patient-provider
      interactions into clinically relevant topics with reasonable accuracy.

PMID- 24285156
TI  - [The social dimension of tuberculosis in the City of Munich].
AB  - Germany is a low-incidence country for tuberculosis, but there is no time for
      complacency. With an annual incidence of 10 per 100,000 population the City of
      Munich counts twice as many cases of tuberculosis compared to the national
      average. Reasons for the concentration of tuberculosis in big cities include the
      high proportion of migrants from countries with high prevalence of tuberculosis
      and from socioeconomically disadvantaged populations. Munich's population is
      growing fast and is expected to exceed 1.5 million in the near future. Migrants
      looking for employment now come predominantly from Romania, Bulgaria and Poland.
      The proportion of foreign born patients with tuberculosis increased over the last
      ten years from 49 to 80 %. Asylum seekers and migrants need special attention
      from the public tuberculosis services. The proportion of tuberculosis patients
      with social problems increased from 37 to 55 % over the last 6 years. Demands for
      medical and social support have increased and the case management is increasingly
      complex. In 2011 the ambulatory treatment of 6 immigrants was supervised by the
      public health services in Munich. Increasingly, uninsured patients from
      southeastern states of the European Union need medical treatment. In Europe the
      overall number of tuberculosis cases is decreasing. The proportion of multidrug
      resistant (MDR) tuberculosis in Eastern Europe is alarming. 15 of worldwide 27
      countries with the highest MDR load are located in the European Region. In Munich
      the number of MDR cases is still low at 1-4 cases each year. But duration, cost
      and side effects of therapy are strong barriers to treatment success. All
      patients have the right to get adequate diagnostic work-up and effective
      treatment no matter in which country they reside. To realize this request with
      cross-border control and care, is a big challenge to the public health service in
      a global perspective.

PMID- 24285157
TI  - [Hygiene control visits in medical practices - topics to be focused on].
AB  - According to the "Protection against Infection Act", public health services are
      obliged to supervise and consult the hygienic conditions not only in hospitals
      but also in ambulatory medical practices in Germany. Firstly, in this paper basic
      principles on transmission routes of pathogenic germs and general remarks on the
      infection control visits as well as on the special regulations (i.e., German
      commission on hospital hygiene and infection prevention) are described. Secondly,
      crucial points to be considered in all medical practices are mentioned. Finally,
      special issues in different practices are reported, such as dermatology,
      gastroenterology, gynaecology, paediatrics etc. This article aims to support the
      public health departments in their task to prevent infections in patients and
      personnel in medical practices..

PMID- 24285158
TI  - [Hydraulic fracturing - a hazard for drinking water?].
AB  - Hydraulic fracturing (fracking) is a technique used to release and promote the
      extraction of natural gas (including shale gas, tight gas, and coal bed methane)
      from deep natural gas deposits. Among the German public there is great concern
      with regard to the potential environmental impacts of fracking including the
      contamination of ground water, the most important source of drinking water in
      Germany. In the present article the risks of ground water contamination through
      fracking are discussed. Due to the present safety requirements and the obligatory
      geological and hydrogeological scrutiny of the underground, which has to be
      performed prior to fracking, the risk of ground water contamination by fracking
      can be regarded as very low. The toxicity of chemical additives of fracking
      fluids is discussed. It is recommended that in the future environmental impact
      assessment and approval of fracs should be performed by the mining authorities in
      close cooperation with the water authorities. Furthermore, it is recommended that
      hydraulic fracturing in the future should be accompanied by obligatory ground
      water monitoring.

PMID- 24285159
TI  - Nitrite complexes of the rare earth elements.
AB  - The coordination chemistry of the nitrite anion has been investigated with rare
      earth elements, and the resulting complexes were structurally characterized.
      Among them, the first homoleptic examples of nitrite complexes of samarium,
      ytterbium and yttrium are described. The coordination behavior of the nitrite ion
      is directly controlled by the ionic radius of the metal cation. While the nitrito
      ligand is stable in the coordination sphere of cerium(iii), it is readily reduced
      by SmI2. 

PMID- 24285161
TI  - Diabetes UK defends its type 2 diabetes awareness campaign.

PMID- 24285160
TI  - The comparison of thrombocytosis and platelet-lymphocyte ratio as potential
      prognostic markers in colorectal cancer.
AB  - The aim of the present study was to analyse the preoperative platelet count and
      the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of
      different stages and with hepatic metastasis of CRC (mCRC) and to compare these
      factors as potential prognostic markers. Clinicopathological data of 10 years
      were collected retrospectively from 336 patients with CRC and 118 patients with
      mCRC. Both in the CRC and the mCRC group overall survival (OS) was significantly
      worse in patients who had elevated platelet count (hazard ratio [HR] = 2.2, p <
      0.001 and HR = 2.9, p = 0.018, respectively). Multivariate analysis indicated
      that elevated platelet count was an independent prognostic factor of CRC (HR =
      1.7, p = 0.035) and mCRC (HR = 3.1, p = 0.017). Disease-free survival (DFS) was
      significantly worse in patients with elevated platelet count in the CRC group (HR
      = 2.0, p = 0.011). In the multivariate analysis the PLR was not a prognostic
      factor in either of the two cohorts (HR = 0.92, p < 0.001 and HR = 0.89, p =
      0.789, respectively). The platelet count is a valuable prognostic marker for the
      survival in patients both with CRC and mCRC while the PLR is not prognostic in
      either group. 

PMID- 24285162
TI  - ADHD is a social problem.

PMID- 24285163
TI  - Loss of Office for National Statistics data will increase health inequalities.

PMID- 24285164
TI  - Attendances at Charing Cross and Hammersmith Hospitals' urgent care centres, 2009
      12.

PMID- 24285165
TI  - Tax on soft drinks to reduce obesity. Lowering the price of "good" foods would be
      better than taxing "bad" foods in reducing obesity.

PMID- 24285166
TI  - Is a tax on sugary drinks too bitter to swallow?

PMID- 24285167
TI  - Information is lacking on health inequalities by sexual orientation.

PMID- 24285168
TI  - Migrant patients' access to HIV care: testing should always be free.

PMID- 24285169
TI  - Still not clear that smoking cessation drugs do not cause psychiatric symptoms.

PMID- 24285170
TI  - Authors' reply to Davies.

PMID- 24285171
TI  - Results from multiagency ADHD pathway in Wolverhampton.

PMID- 24285172
TI  - ADHD is a behavioural construct, not a psychiatric condition.

PMID- 24285173
TI  - Are concerns about DSM-5 ADHD criteria supported by empirical evidence?

PMID- 24285174
TI  - Authors' reply to Cortese.

PMID- 24285175
TI  - Prompt use of neuraminidase inhibitors improves survival of children severely ill
      with flu.

PMID- 24285176
TI  - microRNA miR-17-92 cluster is highly expressed in epidermal Langerhans cells but
      not required for its development.
AB  - Langerhans cells (LCs) are bone marrow-derived immature skin-residential
      dendritic cells (DCs) with a life cycle distinct from that of other types of DCs.
      The mechanisms involved in LC homeostasis and immunological functions are still
      not clear. MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate
      gene expression through either translational repression or mRNA degradation. A
      recent study showed that specific deletion of total miRNAs in DCs affects the
      homeostasis and function of only LCs, but not of other types of DCs. The roles of
      specific individual miRNA in LC development are still lacking. The miRNA miR-17
      92 class, encoding miR-17, miR-18, miR-19a, miR-19b, miR-20 and miR-92, plays a
      very important role in B- and T-cell development and function. Here, we first
      report that epidermal LCs highly express the miR-17-92 class compared with spleen
      naive T cells. To further characterize the role of miR-17-92 in LC development,
      we generated LC-specific miR-17-92 knockout and knock-in mice. Interestingly, LC
      specific gain- and loss-of-function of miR-17-92 cluster did not significantly
      change LC homeostasis, maturation ability, antigen capture and migration to
      draining lymph nodes. Thus, the miR-17-92 cluster may be functionally redundant
      and not critically required for LC development and function. 

PMID- 24285177
TI  - HLA-DPB1 and anti-HBs titer kinetics in hepatitis B booster recipients who
      completed primary hepatitis B vaccination during infancy.
AB  - Previously we reported significant associations of the human leukocyte antigen
      (HLA)-DPB1 05:01 with memory against hepatitis B (HB) vaccination. However, the
      effects of HLA-DPB1 on antibodies to hepatitis B surface antigen (anti-HBs)
      kinetics were not explored. We followed up a cohort of 1974 HB booster recipients
      and quantified their 1-month and 1-year post-booster anti-HBs titers. A total of
      681 subjects were randomly selected and typed for HLA-DPB1. We found that male
      subjects, undetectable pre-booster titers, and 05:01 homozygotes led to
      significantly lower post-booster anti-HBs titers. The geometric means (95%
      confidence interval (CI)) of 1-month post-booster anti-HBs titers were 4.68 (2.69
      8.12), 23.01 (14.96-35.40) and 50.06 (27.20-92.13) mIU ml(-1) for subjects
      carrying two, one and no HLA-DPB1 05:01 allele. The corresponding figures for 1
      year post-booster anti-HBs titers were 1.26 (0.73-2.18), 4.72 (3.08-7.25) and
      7.32 (3.75-13.56) mIU ml(-1). There were significant associations of post-booster
      anti-HBs titers with the number of HLA-DPB1 risk and protective alleles. Among
      booster responders, anti-HBs decay rates were significantly reduced in subjects
      who had detectable pre-booster anti-HBs titers and the HLA-DPB1 05:01 allele. Our
      results indicated that HLA-DPB1 influences the kinetics of anti-HBs. The long
      term memory against hepatitis B surface antigen (HBsAg) and the residual serum
      titers of anti-HBs after HB vaccination may be influenced by different mechanisms
      as evidenced by their inverse trend of associations with the 05:01 allele. 

PMID- 24285178
TI  - Screen of whole blood responses to flagellin identifies TLR5 variation associated
      with outcome in melioidosis.
AB  - Melioidosis is a severe infection caused by the flagellated bacterium
      Burkholderia pseudomallei. The nonsense polymorphism TLR51174C>T is associated
      with improved outcome in Thais with melioidosis. We hypothesized that other TLR5
      variants may modulate the host response and determine outcome in melioidosis. We
      genotyped 12 TLR5 variants selected de novo from the HapMap database and examined
      the association of each with cytokines induced by flagellin stimulation of whole
      blood from healthy Thai subjects. We found a blunted cytokine response for three
      related markers that were in linkage disequilibrium (LD) with a non-synonymous
      variant, TLR51846T>C. Carriers of TLR51846T>C had broadly impaired cytokine
      responses induced by flagellin. TLR51846T>C was associated with protection
      against death in melioidosis patients (odds ratio: 0.62, 95% confidence interval:
      0.42-0.93, P=0.021). We observed no impairment in TLR51846C-dependent nuclear
      factor kappaB activation, however, suggesting an alternative mechanism for the
      effect. We found that TLR51846T>C was in strong LD with TLR51174C>T. Many of the
      blunted cytokine responses observed and the association of TLR51846T>C with
      survival in melioidosis patients may be attributable to TLR51174C>T, but we could
      not exclude an independent effect of TLR51846T>C. These data identify novel
      associations for TLR51846T>C, enhance our understanding of TLR5 genetic
      architecture in Thais and highlight the role of TLR5 in melioidosis. 

PMID- 24285180
TI  - Nonspecific histopathological diagnoses: the impact of partial biopsy and the
      need for a consensus guideline.

PMID- 24285179
TI  - EEF1A2 inactivates p53 by way of PI3K/AKT/mTOR-dependent stabilization of MDM4 in
      hepatocellular carcinoma.
AB  - Mouse Double Minute homolog 4 (MDM4) gene up-regulation often occurs in human
      hepatocellular carcinoma (HCC), but the molecular mechanisms responsible for its
      induction remain poorly understood. Here we investigated the role of the
      phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian
      target of rapamycin (PI3K/AKT/mTOR) axis in the regulation of MDM4 levels in HCC.
      The activity of MDM4 and the PI3K/AKT/mTOR pathway was modulated in human HCC
      cell lines by way of silencing and overexpression experiments. Expression of main
      pathway components was analyzed in an AKT mouse model and human HCCs. MDM4
      inhibition resulted in growth restraint of HCC cell lines both in vitro and in
      vivo. Inhibition of the PI3K-AKT and/or mTOR pathways lowered MDM4 protein levels
      in HCC cells and reactivated p53-dependent transcription. Deubiquitination by
      ubiquitin-specific protease 2a and AKT-mediated phosphorylation protected MDM4
      from proteasomal degradation and increased its protein stability. The eukaryotic
      elongation factor 1A2 (EEF1A2) was identified as an upstream inducer of PI3K
      supporting MDM4 stabilization. Also, we detected MDM4 protein up-regulation in an
      AKT mouse model and a strong correlation between the expression of EEF1A2,
      activated/phosphorylated AKT, and MDM4 in human HCC (each rho > 0.8, P < 0.001).
      Noticeably, a strong activation of this cascade was associated with shorter
      patient survival. CONCLUSION: The EEF1A2/PI3K/AKT/mTOR axis promotes the
      protumorigenic stabilization of the MDM4 protooncogene in human HCC by way of a
      posttranscriptional mechanism. The activation level of the
      EEF1A2/PI3K/AKT/mTOR/MDM4 axis significantly influences the survival probability
      of HCC patients in vivo and may thus represent a promising molecular target.

PMID- 24285181
TI  - Asthma control: how it can be best assessed?
AB  - PURPOSE OF REVIEW: A control-based asthma assessment is recommended by
      guidelines, but questions remain about how to assess the level of asthma control,
      and how current control status relates to future risks and biomarkers of disease
      pathogenesis. This review summarizes recent published data relating to asthma
      control and describes the challenges created by currently available instruments.
      RECENT FINDINGS: The current literature continues to show the widespread use of
      various assessment instruments for asthma control, in particular those with
      composite scores. However, poor correlations exist between the different
      assessment tools, and these instruments lack diagnostic accuracy to differentiate
      uncontrolled asthma. Whereas the concept of asthma control has been extended to
      add an assessment of future risks to the clinical control, clinical asthma
      control as measured by current available assessment tools does not necessary
      relate to the intrinsic disease activity which is typically characterized by
      inflammation in asthma. SUMMARY: The application of asthma control assessment
      represents an improvement in asthma management. The measurement of underlying
      disease activity potentially by biomarkers to assess disease control will lead to
      an improved assessment of the overall control of asthma, and further studies
      addressing this are needed.

PMID- 24285182
TI  - Biomarker sampling of the airways in asthma.
AB  - PURPOSE OF REVIEW: Although there are several known methods by which to sample
      the upper and lower airways in asthmatic patients, new endpoints have emerged
      over the past few years from these sampling techniques that may be useful
      biomarkers. It is both timely and relevant that these endpoints be reviewed in
      the context of their role in asthma and hence as potential biomarkers in asthma.
      RECENT FINDINGS: This article will cover various upper and lower airway sampling
      methods, and the standard and specialized endpoints that can be derived from
      those methods. For the nasal airways, this will include nasal lavage, exhaled
      nasal nitric oxide and acoustic rhinometry. For the lower airways this will
      include induced sputum, bronchoscopy-based methods and exhaled breath. SUMMARY:
      Some methodologies such as bronchoscopy remain limited in their widespread
      clinical application due to their invasive nature. Less invasive techniques such
      as electronic nose and breath condensate have potential biomarker application but
      still require standardization and additional study. It is clear, however, that
      despite the applicability of a given sampling technique, both routine (cells and
      cytokines) and specialized (genomic, phenotypic, hydration) endpoints are
      measurable and should be combined in clinical trial studies to yield maximum
      results in asthma.

PMID- 24285183
TI  - Noninvasive ventilation in acute severe asthma: current evidence and future
      perspectives.
AB  - PURPOSE OF REVIEW: The use of noninvasive positive pressure ventilation (NPPV) is
      often employed for the management of acute respiratory failure as an alternative
      to endotracheal intubation and mechanical ventilation. However, evidence to
      support the application of NPPV use in patients with acute severe asthma is less
      known. RECENT FINDINGS: A paucity of evidence is available to support the use of
      NPPV as part of clinical care in patients with acute severe asthma. A number of
      small studies in adult and paediatric populations suggest that NPPV may have a
      beneficial role through improving respiratory rate and reducing the need for more
      invasive alternatives. Overall NPPV use appeared to be well tolerated with few
      reports of adverse events. SUMMARY: Available evidence is limited by a small
      number of published trials and lack of methodological rigour in existing study
      design. There is a need for well conducted clinical studies to establish accurate
      treatment efficacy, safety and cost-effectiveness, in both the adult and
      paediatric setting.

PMID- 24285185
TI  - Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with
      purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.
AB  - [(18)F]2-Fluoroethyl-p-toluenesulfonate also called [(18)F]2-fluoroethyl tosylate
      has been widely used for labeling radioligands for positron emission tomography
      (PET). [(18)F]2-Fluoroethyl-4-bromobenzenesulfonate, also called [(18)F]2
      fluoroethyl brosylate ([(18)F]F(CH2)2OBs), was used as an alternative
      radiolabeling agent to prepare [(18)F]FEOHOMADAM, a fluoroethoxy derivative of
      HOMADAM, by O-fluoroethylating the phenolic precursor. Purified by reverse-phase
      HPLC, the no-carrier-added [(18)F]F(CH2)2OBs was obtained in an average
      radiochemical yield (RCY) of 35%. The reaction of the purified and dried
      [(18)F]F(CH2)2OBs with the phenolic precursor was performed by heating in DMF and
      successfully produced [(18)F]FEOHOMADAM, after HPLC purification, in RCY of 21%.

PMID- 24285186
TI  - Digitally enhanced thin layer chromatography: further development and some
      applications in isotopic chemistry.
AB  - Improvements to thin layer chromatography (TLC) analysis can be made easily and
      cheaply by the application of digital colour photography and image analysis. The
      combined technique, digitally enhanced TLC (DE-TLC), is applicable to the
      accurate quantification of analytes in mixtures, to reaction monitoring and to
      other typical uses of TLC. Examples are given of the application of digitally
      enhanced TLC to: the deuteromethylations of theophylline to [methyl
      (2)H3]caffeine and of umbelliferone to [(2)H3]7-methoxycoumarin; the selection of
      tertiary amine bases in deuterodechlorination reactions; stoichiometry
      optimisation in the borodeuteride reduction of quinizarin (1,4
      dihydroxyanthraquinone) and to the assessment of xanthophyll yields in Lepidium
      sativum seedlings grown in deuterated media.

PMID- 24285187
TI  - Development of novel PET probes, [18F]BCPP-EF, [18F]BCPP-BF, and [11C]BCPP-EM for
      mitochondrial complex 1 imaging in the living brain.
AB  - We developed three novel positron-emission tomography (PET) probes, 2-tert-butyl
      4-chloro-5-{6-[2-(2[(18)F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin
      3-one ([(18)F]BCPP-EF), 2-tert-butyl-4-chloro-5-[6-(4-[(18) F]fluorobutoxy)
      pyridin-3-ylmethoxy]-2H-pyridazin-3-one ([(18)F]BCPP-BF), and 2-tert-butyl-4
      chloro-5-{6-[2-(2-[(11)C]methoxy-ethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H
      pyridazin-3-one ([(11)C]BCPP-EM), for quantitative imaging of mitochondrial
      complex 1 (MC-1) activity in vivo. These three PET probes were successfully
      labeled by nucleophilic [(18)F]fluorination or by [(11)C]methylation of their
      corresponding precursor with sufficient radioactivity yield, good radiochemical
      purity, and sufficiently high specific radioactivity for PET measurement. The
      specificity of these probes for binding to MC-1 was assessed with rotenone, a
      specific MC-1 inhibitor, by a rat brain slice imaging method in vitro. Rat whole
      body imaging by small-animal PET demonstrated that all probes showed high uptake
      levels in the brain as well as in the heart sufficient to image them clearly. The
      rank order of uptake levels in the brain and the heart just after injection was
      as follows: high in [(18)F]BCPP-BF, intermediate in [(11)C]BCPP-EM, and low in
      [(18) F]BCPP-EF. The kinetics of [(18)F]BCPP-EF and [(11)C]BCPP-EM provided a
      reversible binding pattern, whereas [(18)F]BCPP-BF showed nonreversible
      accumulation-type kinetics in the brain and heart. Metabolite analyses indicated
      that these three compounds were rapidly metabolized in the plasma but relatively
      stable in the rat brain up to 60 min post-injection. The present study
      demonstrated that [(18)F]BCPP-EF could be a useful PET probe for quantitative
      imaging of MC-1 activity in the living brain by PET.

PMID- 24285188
TI  - Novel design and synthesis of a radioiodinated glycolipid analog as an acceptor
      substrate for N-acetylglucosaminyltransferase V.
AB  - Guided by the known molecular recognition interactions between N
      acetylglucosaminyltransferase V (GnT-V) and certain synthetic substrates, we
      synthesized a radiolabeled double-stranded glycolipid composed of a long-chain
      alkyl unit and a radioiodinated phenylalkyl unit, [(125)I]-2-[N-(2-hydroxy-3
      hexadecyloxy)propyl-15-(4-iodophenyl)pentadecanecarboxamido]ethyl 2-acetamido-2
      deoxy-beta-D-glucopyranosyl-(1->2)-alpha-D-mannopyranosyl-(1->6)-beta-D
      glucopyranoside ([(125)I]2), as a novel intravital glycolipid mimic substrate of
      GnT-V. The radioactive iodine ((125)I) was incorporated via iododestannylation of
      the phenyltributyltin derivative, 2-[N-(2-acetoxy-3-hexadecyloxy)propyl-15-(4
      tributylstannylphenyl)pentadecanecarboxamido]ethyl 3,4,6-tri-O-acetyl-2-acetamido
      2-deoxy-beta-D-glucopyranosyl-(1->2)-3,4,6-O-acetyl-alpha-D-mannopyranosyl-(1->6)
      2,3,4-tri-O-acetyl-beta-D-glucopyranoside (26). Subsequent deacetylation at the
      final step afforded [(125)I]2.

PMID- 24285189
TI  - Synthesis and pharmacological evaluation of 99mTc-labeled imidazolyl-containing
      diphosphonic acid as a novel bone imaging agent.
AB  - In order to develop a superior bone imaging agent, a new radiotracer (99m)Tc-1
      hydroxy-5-(2-butyl-1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (BIPeDP)
      was designed and prepared with good radiochemical yield and stability. The
      biodistribution in mice shows that (99m)Tc-BIPeDP has high specificity in the
      skeleton with the maximum uptake of 17.30 +/- 0.14 injected dose per gram at 60
      min. Kinetics of blood clearance shows that the distribution half-life
      (T1/2alpha) and elimination half-life (T1/2beta) of (99m)Tc-BIPeDP are 3.7 and
      49.7 min, respectively. An excellent image can be obtained at 1-h post-injection
      with the single photon emission computed tomography bone scanning, which is
      clearer and quicker than (99m)Tc-zoledronic acid, (99m)Tc-1-hydroxy-5-(1H
      imidazol-1-yl)pentane-1,1-diyldiphosphonic acid, and (99m)Tc
      methylenediphosphonic acid All results indicate that (99m)Tc-BIPeDP holds great
      potential as a novel promising bone imaging agent.

PMID- 24285191
TI  - An efficient laboratory-scale preparative method for [1-(13)C]glycocholic acid.
AB  - A breath test using [1-(13)C]glycocholic acid as a substrate is a potential
      diagnostic method for small intestinal bacterial overgrowth syndrome. [1
      (13)C]Glycocholic acid has been thus synthesized in an excellent yield from ethyl
      [1-(13)C]glycinate hydrochloride in a one-pot reaction. This method is suitable
      for the preparation of the labeled compound on a laboratory scale, which helps to
      perform extensive clinical studies of the breath test.

PMID- 24285190
TI  - A general route for 13C-labeled fluorenols and phenanthrenols via palladium
      catalyzed cross-coupling and one-carbon homologation.
AB  - A series of (13)C-labeled polyaromatic hydrocarbons (PAHs), fluorenols and
      phenanthrenols were synthesized from commercially available (13)C-labeled
      starting material giving rise to M + 6 isotopomers. This was accomplished using
      key palladium-catalyzed cross-coupling and one-carbon homologation strategies.
      The conditions for these reactions were optimized, and the new chemical routes
      are efficient in the number of chemical steps, can be scaled to afford gram
      quantities and occur in good yields based on the (13)C label. These labeled
      compounds as precursors for more complex PAHs and are useful as internal
      standards in mass spectrometry and NMR spectroscopy studies for monitoring
      environmental contamination and biological exposure to PAHs and their
      metabolites.

PMID- 24285193
TI  - Evolutionary origins and diversification of proteobacterial mutualists.
AB  - Mutualistic bacteria infect most eukaryotic species in nearly every biome.
      Nonetheless, two dilemmas remain unresolved about bacterial-eukaryote mutualisms:
      how do mutualist phenotypes originate in bacterial lineages and to what degree do
      mutualists traits drive or hinder bacterial diversification? Here, we
      reconstructed the phylogeny of the hyperdiverse phylum Proteobacteria to
      investigate the origins and evolutionary diversification of mutualistic bacterial
      phenotypes. Our ancestral state reconstructions (ASRs) inferred a range of 34-39
      independent origins of mutualist phenotypes in Proteobacteria, revealing the
      surprising frequency with which host-beneficial traits have evolved in this
      phylum. We found proteobacterial mutualists to be more often derived from
      parasitic than from free-living ancestors, consistent with the untested paradigm
      that bacterial mutualists most often evolve from pathogens. Strikingly, we
      inferred that mutualists exhibit a negative net diversification rate (speciation
      minus extinction), which suggests that mutualism evolves primarily via
      transitions from other states rather than diversification within mutualist taxa.
      Moreover, our ASRs infer that proteobacterial mutualist lineages exhibit a
      paucity of reversals to parasitism or to free-living status. This evolutionary
      conservatism of mutualism is contrary to long-standing theory, which predicts
      that selection should often favour mutants in microbial mutualist populations
      that exploit or abandon more slowly evolving eukaryotic hosts. 

PMID- 24285194
TI  - The effect of socio-economic status and food availability on first birth interval
      in a pre-industrial human population.
AB  - Individual variation in nutritional status has direct implications for fitness
      and thus is crucial in shaping patterns of life-history variation. Nevertheless,
      it is difficult to measure in natural populations, especially in humans. Here, we
      used longitudinal data on individual life-histories and annual crop yield
      variation collected from pre-industrial Finnish populations experiencing natural
      mortality and fertility to test the validity of first birth interval (FBI; time
      between marriage and first birth) as a surrogate measure of nutritional status.
      We evaluated whether women with different socio-economic groups differ in length
      of FBI, whether women of poorer socio-economic status and experiencing lower crop
      yields conceive slower following marriage, and whether shorter FBI is associated
      with higher lifetime breeding success. We found that poorer women had longer FBI
      and reduced probability of giving birth in months with low food availability,
      while the FBI of richer women was not affected by variation in food availability.
      Women with shorter FBI achieved higher lifetime breeding success and a faster
      reproductive rate. This is, to our knowledge, the first study to show a direct
      relationship between environmental conditions and speed of childbirth following
      marriage, highlighting the value of FBI as an indicator of nutritional status
      when direct data are lacking. 

PMID- 24285195
TI  - Experimental evidence for friction-enhancing integumentary modifications of
      chameleons and associated functional and evolutionary implications.
AB  - The striking morphological convergence of hair-like integumentary derivatives of
      lizards and arthropods (spiders and insects) demonstrates the importance of such
      features for enhancing purchase on the locomotor substrate. These pilose
      structures are responsible for the unique tractive abilities of these groups of
      animals, enabling them to move with seeming ease on overhanging and inverted
      surfaces, and to traverse inclined smooth substrates. Three groups of lizards are
      well known for bearing adhesion-promoting setae on their digits: geckos, anoles
      and skinks. Similar features are also found on the ventral subdigital and distal
      caudal skin of chameleons. These have only recently been described in any detail,
      and structurally and functionally are much less well understood than are the
      setae of geckos and anoles. The seta-like structures of chameleons are not
      branched (a characteristic of many geckos), nor do they terminate in spatulate
      tips (which is characteristic of geckos, anoles and skinks). They are densely
      packed and have attenuated blunt, globose tips or broad, blade-like shafts that
      are flattened for much of their length. Using a force transducer, we tested the
      hypothesis that these structures enhance friction and demonstrate that the pilose
      skin has a greater frictional coefficient than does the smooth skin of these
      animals. Our results are consistent with friction being generated as a result of
      side contact of the integumentary filaments. We discuss the evolutionary and
      functional implications of these seta-like structures in comparison with those
      typical of other lizard groups and with the properties of seta-mimicking
      synthetic structures. 

PMID- 24285196
TI  - A parent-of-origin effect on honeybee worker ovary size.
AB  - Apis mellifera capensis is unique among honeybees in that unmated workers can
      produce pseudo-clonal female offspring via thelytokous parthenogenesis. Workers
      use this ability to compete among themselves and with their queen to be the
      mother of new queens. Males could therefore enhance their reproductive success by
      imprinting genes that enhance fertility in their daughter workers. This
      possibility sets the scene for intragenomic conflict between queens and drones
      over worker reproductive traits. Here, we show a strong parent-of-origin effect
      for ovary size (number of ovarioles) in reciprocal crosses between two honeybee
      subspecies, A. m. capensis and Apis mellifera scutellata. In this cross, workers
      with an A. m. capensis father had 30% more ovarioles than genotypically matched
      workers with an A. m. scutellata father. Other traits we measured (worker weight
      at emergence and the presence/absence of a spermatheca) are influenced more by
      rearing conditions than by parent-of-origin effects. Our study is the first to
      show a strong epigenetic (or, less likely, cytoplasmic maternal) effect for a
      reproductive trait in the honeybee and suggests that a search for parent-of
      origin effects in other social insects may be fruitful. 

PMID- 24285197
TI  - Increased brain size in mammals is associated with size variations in gene
      families with cell signalling, chemotaxis and immune-related functions.
AB  - Genomic determinants underlying increased encephalization across mammalian
      lineages are unknown. Whole genome comparisons have revealed large and frequent
      changes in the size of gene families, and it has been proposed that these
      variations could play a major role in shaping morphological and physiological
      differences among species. Using a genome-wide comparative approach, we examined
      changes in gene family size (GFS) and degree of encephalization in 39 fully
      sequenced mammalian species and found a significant over-representation of GFS
      variations in line with increased encephalization in mammals. We found that this
      relationship is not accounted for by known correlates of brain size such as
      maximum lifespan or body size and is not explained by phylogenetic relatedness.
      Genes involved in chemotaxis, immune regulation and cell signalling-related
      functions are significantly over-represented among those gene families most
      highly correlated with encephalization. Genes within these families are
      prominently expressed in the human brain, particularly the cortex, and organized
      in co-expression modules that display distinct temporal patterns of expression in
      the developing cortex. Our results suggest that changes in GFS associated with
      encephalization represent an evolutionary response to the specific functional
      requirements underlying increased brain size in mammals. 

PMID- 24285198
TI  - Adaptive value of same-sex pairing in Laysan albatross.
AB  - Same-sex pairing is widespread among animals but is difficult to explain in an
      evolutionary context because it does not result in reproduction, and thus same
      sex behaviour often is viewed as maladaptive. Here, we compare survival,
      fecundity and transition probabilities of female Laysan albatross in different
      pair types, and we show how female-female pairing could be an adaptive
      alternative mating strategy, albeit one that resulted in lower fitness than male
      female pairing. Females in same-sex pairs produced 80% fewer chicks, had lower
      survival and skipped breeding more often than those in male-female pairs. Females
      in same-sex pairs that raised a chick sometimes acquired a male mate in the
      following year, but females in failed same-sex pairs never did, suggesting that
      males exert sexual selection by assessing female quality and relegating low
      quality females into same-sex pairs. Sexual selection by males in a monomorphic,
      non-ornamented species is rare and suggests that reconsideration is needed of the
      circumstances in which alternative reproductive behaviour evolves. Given the lack
      of males and obligate biparental care in this species, this research demonstrates
      how same-sex pairing was better than not breeding and highlights how it could be
      an adaptive strategy under certain demographic conditions. 

PMID- 24285199
TI  - Adaptation through genetic time travel? Fluctuating selection can drive the
      evolution of bacterial transformation.
AB  - Natural transformation is a process whereby bacteria actively take up DNA from
      the surrounding environment and incorporate it into their genome. Natural
      transformation is widespread in bacteria, but its evolutionary significance is
      still debated. Here, we hypothesize that transformation may confer a fitness
      advantage in changing environments through a process we term 'genetic time
      travel': by taking up old genes that were retained in the environment, the
      bacteria may revert to a past genotypic state that proves advantageous in the
      present or a future environment. We scrutinize our hypothesis by means of a
      mathematical model involving two bacterial types (transforming and non
      transforming), a single locus under natural selection and a free DNA pool. The
      two bacterial types were competed in environments with changing selection
      regimes. We demonstrate that for a wide range of parameter values for the DNA
      turnover rate, the transformation rate and the frequency of environmental change,
      the transforming type outcompetes the non-transforming type. We discuss the
      empirical plausibility of our hypothesis, as well as its relationship to other
      hypotheses for the evolution of transformation in bacteria and sex more
      generally, speculating that 'genetic time travel' may also be relevant in
      eukaryotes that undergo horizontal gene transfer. 

PMID- 24285200
TI  - A living fossil tale of Pangaean biogeography.
AB  - The current distributions of widespread groups of terrestrial animals and plants
      are supposedly the result of a mixture of either vicariance owing to continental
      split or more recent trans-oceanic dispersal. For organisms exhibiting a
      vicariant biogeographic pattern-achieving their current distribution by riding on
      the plates of former supercontinents-this view is largely inspired by the belief
      that Pangaea lacked geographical or ecological barriers, or that extinctions and
      dispersal would have erased any biogeographic signal since the early Mesozoic. We
      here present a time-calibrated molecular phylogeny of Onychophora (velvet worms),
      an ancient and exclusively terrestrial panarthropod group distributed throughout
      former Pangaean landmasses. Our data not only demonstrate that trans-oceanic
      dispersal does not need be invoked to explain contemporary distributions, but
      also reveal that the early diversification of the group pre-dates the break-up of
      Pangaea, maintaining regionalization even in landmasses that have remained
      contiguous throughout the history of the group. These results corroborate a
      growing body of evidence from palaeontology, palaeogeography and palaeoclimatic
      modelling depicting ancient biogeographic regionalization over the continuous
      landmass of Pangaea. 

PMID- 24285201
TI  - Manipulating the appearance of a badge of status causes changes in true badge
      expression.
AB  - Signals of dominance and fighting ability (i.e. status signals) are found in a
      wide range of taxa and are used to settle disputes between competitive rivals.
      Most previous research has considered status-signal phenotype as an attribute of
      the individual; however, it is more likely that signal expression is an emergent
      property that also incorporates aspects of the social environment. Furthermore,
      because an individual's signal phenotype is likely to influence its social
      interactions, the relationships between status signals, social environment and
      individual quality are probably much more complex than previously appreciated.
      Here, we explore the dynamic relationship between social interactions and signal
      expression in a previously undescribed status signal, the frontal shield of the
      pukeko (Porphyrio porphyrio melanotus: Aves). We demonstrate that frontal shield
      size is a strong predictor of dominance status within social groups, even after
      controlling for potentially confounding variables. Then, we evaluate the
      relationship between social interactions and signal expression by testing whether
      manipulating apparent shield size influences (i) dominance interactions and (ii)
      future signal expression. By showing that decreasing apparent shield size causes
      both an increase in the amount of aggression received and a decrease in an
      individual's true shield size, we provide the first evidence of dynamic feedback
      between signal expression and social interactions. Our study provides important
      insight into the role of receiver-dependent (i.e. social) costs in maintaining
      signal honesty and demonstrates a unique approach to studying status signalling
      applicable to future studies on dynamic morphological signals. 

PMID- 24285202
TI  - A role for iron and oxygen chemistry in preserving soft tissues, cells and
      molecules from deep time.
AB  - The persistence of original soft tissues in Mesozoic fossil bone is not explained
      by current chemical degradation models. We identified iron particles (goethite
      alphaFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs,
      using transmission electron microscopy, electron energy loss spectroscopy, micro
      X-ray diffraction and Fe micro-X-ray absorption near-edge structure. Iron
      chelators increased fossil tissue immunoreactivity to multiple antibodies
      dramatically, suggesting a role for iron in both preserving and masking proteins
      in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200
      fold, from approximately 3 days to more than two years at room temperature (25
      degrees C) in an ostrich blood vessel model developed to test post-mortem 'tissue
      fixation' by cross-linking or peroxidation. HB-induced solution hypoxia coupled
      with iron chelation enhances preservation as follows: HB + O2 > HB - O2 > -O2 >>
      +O2. The well-known O2/haeme interactions in the chemistry of life, such as
      respiration and bioenergetics, are complemented by O2/haeme interactions in the
      preservation of fossil soft tissues.

PMID- 24285205
TI  - [Middle ear tuberculosis - a forgotten, but not vanished illness].

PMID- 24285203
TI  - CO2-induced ocean acidification increases anxiety in rockfish via alteration of
      GABAA receptor functioning.
AB  - The average surface pH of the ocean is dropping at a rapid rate due to the
      dissolution of anthropogenic CO2, raising concerns for marine life. Additionally,
      some coastal areas periodically experience upwelling of CO2-enriched water with
      reduced pH. Previous research has demonstrated ocean acidification (OA)-induced
      changes in behavioural and sensory systems including olfaction, which is due to
      altered function of neural gamma-aminobutyric acid type A (GABAA) receptors.
      Here, we used a camera-based tracking software system to examine whether OA
      dependent changes in GABAA receptors affect anxiety in juvenile Californian
      rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that
      measure light/dark preference (scototaxis) and proximity to an object. After one
      week in OA conditions projected for the next century in the California shore
      (1125 +/- 100 uatm, pH 7.75), anxiety was significantly increased relative to
      controls (483 +/- 40 uatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but
      not the antagonist gabazine, caused a significant increase in anxiety consistent
      with altered Cl(-) flux in OA-exposed fish. OA-exposed fish remained more anxious
      even after 7 days back in control seawater; however, they resumed their normal
      behaviour by day 12. These results show that OA could severely alter rockfish
      behaviour; however, this effect is reversible. 

PMID- 24285207
TI  - [Is the physician the insurance broker for his patients?].

PMID- 24285208
TI  - [Diagnosis and therapy of bleeding in ENT].
AB  - Bleeding in the oral cavity, nose or ear are common events in the daily routine
      of ENT specialists. Apart from trivial cases that often get outpatient treatment,
      there are numerous cases of serious bleeding that require stationary treatment
      and if necessary, an operative or interventional therapy. In the following
      section the most frequent types of bleeding, their diagnosis and therapy will be
      explained.

PMID- 24285209
TI  - [Symptom related, realistic goals of surgical interventions in patients with
      rhinosinusitis].

PMID- 24285213
TI  - Fluorine insertion into the Ruddlesden-Popper phase La2BaFe2O7: the structure and
      magnetic properties of La2BaFe2O5F4.
AB  - Fluorination of the n = 2 Ruddlesden-Popper phase La2BaFe2O7 occurs at ~300 
      degrees C in flowing 10% F2 in N2 to form La2BaFe2O5F4. This oxide fluoride
      contains 2F(-) ions in interstitial sites within the rocksalt regions and 2F(-)
      ions that have substituted for O(2-) ions in apical sites within the rocksalt
      layers. The fluorination results in an expansion along c of 7.6% to yield a
      tetragonal unit cell of dimensions a = 3.96237(7) A, c = 22.3972(5) A. The
      structure and magnetic properties have been examined by Mossbauer spectroscopy,
      neutron powder diffraction and magnetic susceptibility measurements. La2BaFe2O5F4
      becomes antiferromagnetically ordered at temperatures below ~500 K, and the
      magnetic order shows a striking resemblance to that observed in La2BaFe2O7. The
      magnetic moments on Fe(3+) are perpendicular to [001] and aligned along +/-{100}
      directions above 300 K, but at temperatures below 200 K, they rotate by 45
      degrees  to lie along +/-{110}. Mossbauer spectroscopy suggests the presence of
      Fe(3+) within the primary phase, but also indicates that fluorination results in
      some particle fragmentation to form a paramagnetic component of the fluorinated
      material.

PMID- 24285211
TI  - EEG power asymmetry and functional connectivity as a marker of treatment
      effectiveness in DBS surgery for depression.
AB  - Recently, deep brain stimulation (DBS) has been evaluated as an experimental
      therapy for treatment-resistant depression. Although there have been encouraging
      results in open-label trials, about half of the patients fail to achieve
      meaningful benefit. Although progress has been made in understanding the
      neurobiology of MDD, the ability to characterize differences in brain dynamics
      between those who do and do not benefit from DBS is lacking. In this study, we
      investigated EEG resting-state data recorded from 12 patients that have undergone
      DBS surgery. Of those, six patients were classified as responders to DBS, defined
      as an improvement of 50% or more on the 17-item Hamilton Rating Scale for
      Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha
      power asymmetry and synchronization asymmetry between responders and non
      responders. Hemispheric power asymmetry showed statistically significant
      differences between responders and non-responders with healthy controls showing
      an asymmetry similar to responders but opposite to non-responders. This asymmetry
      was characterized by an increase in frontal theta in the right hemisphere
      relative to the left combined with an increase in parietal alpha in the left
      hemisphere relative to the right in non-responders compared with responders.
      Hemispheric mean synchronization asymmetry showed a statistically significant
      difference between responders and non-responders in the theta band, with healthy
      controls showing an asymmetry similar to responders but opposite to non
      responders. This asymmetry resulted from an increase in frontal synchronization
      in the right hemisphere relative to the left combined with an increase in
      parietal synchronization in the left hemisphere relative to the right in non
      responders compared with responders. Connectivity diagrams revealed long-range
      differences in frontal/central-parietal connectivity between the two groups in
      the theta band. This pattern was observed irrespective of whether EEG data were
      collected with active DBS or with the DBS stimulation turned off, suggesting
      stable functional and possibly structural modifications that may be attributed to
      plasticity. 

PMID- 24285214
TI  - Low-affinity FcgammaR interactions can decide the fate of novel human IgG
      sensitised red blood cells and platelets.
AB  - G1Deltanab is a mutant human IgG1 constant region with a lower ability to
      interact with FcgammaR than the natural IgG constant regions. Radiolabelled RBCs
      and platelets sensitised with specific G1Deltanab Abs were cleared more slowly
      from human circulation than IgG1-sensitised counterparts. However, non
      destructive splenic retention of G1Deltanab-coated RBCs required investigation
      and plasma radioactivities now suggest this also occurred for platelets
      sensitised with an IgG1/G1Deltanab mixture. In vitro assays with human cells
      showed that G1Deltanab-sensitised RBCs did not cause FcgammaRI-mediated monocyte
      activation, FcgammaRIIIa-mediated antibody-dependent cell-mediated cytotoxicity
      (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus,
      FcgammaRII was implicated in the adhesion despite the Deltanab mutation reducing
      the already low-affinity binding to this receptor class. Additional contacts via
      P-selectin enhance the interaction of sensitised platelets with monocytes and
      this system provided evidence of FcgammaRII-dependent activation by G1Deltanab.
      These results emphasise the physiological relevance of low-affinity interactions:
      It appears that FcgammaRII interactions of G1Deltanab allowed splenic retention
      of G1Deltanab-coated RBCs with inhibitory FcgammaRIIb binding preventing RBC
      destruction and that FcgammaRIIb engagement by G1Deltanab on IgG1/G1Deltanab
      sensitised platelets overcame activation by IgG1. Considering therapeutic
      blocking Abs, G1Deltanab offers lower FcgammaR binding and a greater bias towards
      inhibition than IgG2 and IgG4 constant regions. 

PMID- 24285215
TI  - Intratumoral gene therapy versus intravenous gene therapy for distant metastasis
      control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral
      vector-p53.
AB  - Lung cancer still remains to be challenged by novel treatment modalities. Novel
      locally targeted routes of administration are a methodology to enhance treatment
      and reduce side effects. Intratumoral gene therapy is a method for local
      treatment and could be used either in early-stage lung cancer before surgery or
      at advanced stages as palliative care. Novel non-viral vectors are also in demand
      for efficient gene transfection to target local cancer tissue and at the same
      time protect the normal tissue. In the current study, C57BL/6 mice were divided
      into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy.
      The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral
      Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the
      company Addgene for the first time. The aim of the study was to evaluate the
      safety and efficacy of targeted gene therapy in a Lewis lung cancer model.
      Indeed, although the pharmacokinetics of the different administration modalities
      differs, the intratumoral administration presented increased survival and
      decreased distant metastasis. Intratumoral gene therapy could be considered as an
      efficient local therapy for lung cancer. 

PMID- 24285216
TI  - A compact dual promoter adeno-associated viral vector for efficient delivery of
      two genes to dorsal root ganglion neurons.
AB  - Adeno-associated viral (AAV) vectors based on serotype 5 are an efficient means
      to target dorsal root ganglia (DRG) to study gene function in the primary sensory
      neurons of the peripheral nervous system. In this study, we have developed a
      compact AAV dual promoter vector composed of the cytomegalovirus (CMV) and
      chicken beta-actin (CAG) promoters in a back-to-back configuration with a shared
      enhancer, and show efficient expression of two proteins simultaneously in DRG
      neurons. We demonstrate how this is useful for experiments on axonal
      regeneration, by co-expressing a gene of interest and an axonal marker. Using a
      farnesylated form of eGFP, which is actively transported along axons, we show
      superior long-distance labelling of axons of DRG neurons compared with normal
      eGFP. Additionally, we have efficiently transduced lumbar DRG neurons by
      injecting the AAV dual promoter vector into the dorsal intrathecal space, which
      is a less invasive delivery method. In summary, we have developed an AAV dual
      promoter vector designed for simultaneous expression of a gene of interest and a
      fluorescent protein to label long-distance axonal projections, which allows
      specific quantification of axons from transduced neurons after injury. 

PMID- 24285217
TI  - In the rat liver, Adenoviral gene transfer efficiency is comparable to AAV.
AB  - Adenoviral (AdV) and Adenovirus-associated viral (AAV) vectors both are used for
      in vivo gene therapy of inherited liver disorders, such as Crigler-Najjar
      syndrome type 1. In a relevant animal model, the Gunn rat, both vectors
      efficiently correct the severe hyperbilirubinemia characteristic of this liver
      disorder. Although the clinical use of AAV is more advanced, as demonstrated by
      the successful phase 1 trial in hemophilia B patients, because of its large
      cloning capacity AdV remains an attractive option. A direct comparison of the
      efficacy of these two vectors in the liver in a relevant disease model has not
      been reported. Aim of this study was to compare the efficiency of clinically
      applicable doses of both vectors in the Gunn rat. AdV or scAAV (self
      complimentary AAV) ferrying identical liver-specific expression cassettes of the
      therapeutic gene, UGT1A1, were injected into the tail vein. As the titration
      methods of these two vectors are very different, a comparison based on vector
      titers is not valid. Therefore, their efficacy was compared by determining the
      amount of vector genomes delivered to the liver required for therapeutic
      correction of serum bilirubin. Like AAV, the liver-specific first-generation AdV
      also provided sustained correction in this relevant disease model. UGT1A1 mRNA
      expression provided per genome was comparable for both vectors. Flanking the
      expression cassette in AdV with AAV-ITRs (inverted terminal repeats), increased
      UGT1A1 mRNA expression eightfold which resulted in a significant improvement of
      efficacy. Compared with AAV, less AdV genomes were needed for complete correction
      of hyperbilirubinemia. 

PMID- 24285219
TI  - Significant reduction of thermal conductivity in silicon nanowire arrays.
AB  - Vertically aligned single-crystal silicon nanowire arrays (SiNWs) with various
      lengths, surface roughnesses and porosities were fabricated with the metal
      assisted chemical etching method. Using the laser flash technique and
      differential scanning calorimetry, we characterized the thermal conductivities of
      bulk SiNWs/Si/SiNWs sandwich-structured composites (SSCs) at room temperature
      (300 K). The results demonstrate that the thermal conductivities of SSCs notably
      decrease with increases in the length, surface roughness and porosity of SiNWs.
      Furthermore, based on the series thermal-resistance model, we calculated the
      thermal conductivity of porous SiNWs to be as low as 1.68 W m(-1) K(-1) at 300 K.
      Considering the remarkable phonon scattering from the diameter, surface roughness
      and porosity of SiNWs, leading to a significant reduction of the thermal
      conductivity, SSCs and SiNWs could be applied to high-performance thermoelectric
      devices.

PMID- 24285220
TI  - Controlling chloride ions diffusion in concrete.
AB  - The corrosion of steel in concrete is mainly due to the chemical reaction between
      the chloride ions and iron ions. Indeed, this is a serious threaten for
      reinforced concrete structure, especially for the reinforced concrete structure
      in the sea. So it is urgent and important to protect concrete against chloride
      ions corrosion. In this work, we report multilayer concrete can cloak chloride
      ions. We formulated five kinds of concrete A, B, C, D and E, which are made of
      different proportion of cement, sand and glue, and fabricated six-layer (ABACAD)
      cylinder diffusion cloak and background media E. The simulation results show that
      the six-layer mass diffusion cloak can protect concrete against chloride ions
      penetration, while the experiment results show that the concentration gradients
      are parallel and equal outside the outer circle in the diffusion flux lines, the
      iso-concentration lines are parallel outside the outer circle, and the
      concentration gradients in the inner circle are smaller than those outside the
      outer circle. 

PMID- 24285221
TI  - The spin-spin zero-field splitting tensor in the projector-augmented-wave method.
AB  - The projector-augmented-wave (PAW) method of electronic calculations has the
      unique feature that, while it is basically a pseudopotential-like treatment of
      density functional theory, it keeps a connection to reconstructible all-electron
      wavefunctions, and thus it can be considered less an approximation, yet having
      generally the same computational cost when it is compared to pseudopotential
      methods. The zero-field splitting of spin-spin interaction energy, although it is
      a core instrument in the treatment of a wide range of problems involving the
      behavior of electron spins in various materials, has not yet been implemented in
      PAW. We provide here all the background considerations for implementing the
      calculation of the zero-field splitting tensor within the framework of PAW. 

PMID- 24285218
TI  - Suicide gene approach using a dual-expression lentiviral vector to enhance the
      safety of ex vivo gene therapy for bone repair.
AB  - 'Ex vivo' gene therapy using viral vectors to overexpress BMP-2 is shown to heal
      critical-sized bone defects in experimental animals. To increase its safety, we
      constructed a dual-expression lentiviral vector to overexpress BMP-2 or
      luciferase and an HSV1-tk analog, Deltatk (LV-Deltatk-T2A-BMP-2/Luc). We
      hypothesized that administering ganciclovir (GCV) will eliminate the transduced
      cells at the site of implantation. The vector-induced expression of BMP-2 and
      luciferase in a mouse stromal cell line (W-20-17 cells) and mouse bone marrow
      cells (MBMCs) was reduced by 50% compared with the single-gene vector. W-20-17
      cells were more sensitive to GCV compared with MBMCs (90-95% cell death at 12
      days with GCV at 1 MUg ml(-1) in MBMCs vs 90-95% cell death at 5 days by 0.1 MUg
      ml(-1) of GCV in W-20-17 cells). Implantation of LV-Deltatk-T2A-BMP-2 transduced
      MBMCs healed a 2 mm femoral defect at 4 weeks. Early GCV treatment (days 0-14)
      postoperatively blocked bone formation confirming a biologic response. Delayed
      GCV treatment starting at day 14 for 2 or 4 weeks reduced the luciferase signal
      from LV-Deltatk-T2A-Luc-transduced MBMCs, but the signal was not completely
      eliminated. These data suggest that this suicide gene strategy has potential for
      clinical use in the future, but will need to be optimized for increased
      efficiency.

PMID- 24285222
TI  - Abdominal obesity validates the association between elevated alanine
      aminotransferase and newly diagnosed diabetes mellitus.
AB  - To examine how elevated alanine aminotransferase (ALT) could be associated with
      newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a
      mass health examination. The odds ratios (ORs) for diabetes mellitus and newly
      diagnosed diabetes mellitus were compared between people with and without
      abdominal obesity, together with and without elevated ALT levels. 5499 people
      were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis
      of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was
      vigorously associated with diabetes mellitus and newly diagnosed diabetes
      mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not.
      However, coexisting with obesity, elevated ALTs were robustly associated with
      diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of
      newly diagnosed diabetes mellitus, in comparison to non-obese people with normal
      ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had
      significantly higher ORs (obese with ALT <= 40 U/L: 4.7%, OR 1.73, 95% CI 1.08
      2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81
      120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44,
      95% CI 3.04-18.18, P < 0.001). Abdominal obesity validates the association
      between elevated alanine aminotransferase and diabetes mellitus and newly
      diagnosed diabetes mellitus. People with abdominal obesity, especially with
      coexisting elevated ALT levels should be screened for undiagnosed diabetes
      mellitus. 

PMID- 24285223
TI  - Structure-activity relationship of the pro- and anticoagulant effects of Fucus
      vesiculosus fucoidan.
AB  - Fucoidan is a highly complex sulfated polysaccharide commonly extracted from
      brown seaweed. In addition to their many biological activities, fucoidans have
      recently been demonstrated to inhibit or increase coagulation at different
      concentration ranges. Their structural features, i.e. molecular weight (Mw), Mw
      distribution, degree of sulfation, monosaccharide composition, and different
      linkages, are known to affect these activities. Therefore, structure-activity
      relationship (SAR) analysis of fucoidan is crucial for its potential use as a
      procoagulant. In this study, Fucus vesiculosus (F.v.) fucoidan was fractionated
      by charge and size as well as over- and desulfated to different degrees to yield
      preparations with various structural properties. The fractions' pro- and
      anticoagulant activities were assessed by calibrated automated thrombography
      (CAT) and activated partial thromboplastin time(aPTT) assays. Binding to and
      inhibition of the anticoagulant protein tissue factor pathway inhibitor (TFPI)
      and the ability to activate coagulation via the contact pathway were also
      investigated. This paper discusses the impact of charge density, size, and sugar
      composition on fucoidan's pro- and anticoagulant activities. Fucoidan requires a
      minimal charge density of 0.5 sulfates per sugar unit and a size of 70 sugar
      units to demonstrate desired procoagulant activities for improvement of
      haemostasis in factor VIII/factor IX-deficient plasma. 

PMID- 24285224
TI  - Fecal microbiomes of non-human primates in Western Uganda reveal species-specific
      communities largely resistant to habitat perturbation.
AB  - Primate gastrointestinal microbial communities are becoming increasingly
      appreciated for their relevance to comparative medicine and conservation, but the
      factors that structure primate "microbiomes" remain controversial. This study
      examined a community of primates in Kibale National Park, Uganda, to assess the
      relative importance of host species and location in structuring gastrointestinal
      microbiomes. Fecal samples were collected from primates in intact forest and from
      primates in highly disturbed forest fragments. People and livestock living nearby
      were also included, as was a geographically distant population of related red
      colobus in Kenya. A culture-free microbial community fingerprinting technique was
      used to analyze fecal microbiomes from 124 individual red colobus (Procolobus
      rufomitratus), 100 individual black-and-white colobus (Colobus guereza), 111
      individual red-tailed guenons (Cercopithecus ascanius), 578 human volunteers, and
      364 domestic animals, including cattle (Bos indicus and B. indicus * B. taurus
      crosses), goats (Caprus hircus), sheep (Ovis aries), and pigs (Sus scrofa).
      Microbiomes sorted strongly by host species, and forest fragmentation did not
      alter this pattern. Microbiomes of Kenyan red colobus sorted distinctly from
      microbiomes of Ugandan red colobus, but microbiomes from these two red colobus
      populations clustered more closely with each other than with any other species.
      Microbiomes from red colobus and black-and-white colobus were more differentiated
      than would be predicted by the phylogenetic relatedness of these two species,
      perhaps reflecting heretofore underappreciated differences in digestive
      physiology between the species. Within Kibale, social group membership influenced
      intra-specific variation among microbiomes. However, intra-specific variation was
      higher among primates in forest fragments than among primates in intact forest,
      perhaps reflecting the physical separation of fragments. These results suggest
      that, in this system, species-specific processes such as gastrointestinal
      physiology strongly structure microbial communities, and that primate microbiomes
      are relatively resistant to perturbation, even across large geographic distances
      or in the face of habitat disturbance.

PMID- 24285225
TI  - Formulary availability and regulatory barriers to accessibility of opioids for
      cancer pain in Africa: a report from the Global Opioid Policy Initiative (GOPI).
AB  - With nearly 1.1 billion inhabitants living in more than 50 countries, Africa is
      the world's poorest and most socioeconomically underdeveloped continent. Despite
      some advances for individual states, many African countries have very low opioid
      consumption and, overall, the continent has the lowest consumption per capita of
      any in the world. This article presents the findings of the first systematic
      study of the availability and accessibility of opioids for the management of
      cancer pain across the continent. Data are reported on the availability and
      accessibility of opioids for the management of cancer pain in 25 of 52 countries,
      with 744 million of the region's 1127 million people (66%) covered by the survey.
      Many countries had severely restricted formularies of opioids and only 15 of 25
      had morphine available in oral IR, CR and injectable formulations. Even when
      opioids are on formulary they are often unavailable, and access is significantly
      impaired by widespread over-regulation that is pervasive across the region. 

PMID- 24285226
TI  - Formulary availability and regulatory barriers to accessibility of opioids for
      cancer pain in Asia: a report from the Global Opioid Policy Initiative (GOPI).
AB  - Asia is a heterogeneous region with substantial variability in economic, social
      and palliative care development. While the global consumption of opioids has
      increased, the consumption in most Asian countries has not increased at the same
      rate. This is the first comprehensive study of opioid availability and
      accessibility for cancer patients in Asia. Data are reported on the availability
      and accessibility of opioids for the management of cancer pain in 20 of 28
      countries. The countries in the report represent 2515 million of the region's
      2612 million people (96%). With the exception of Japan and South Korea, opioid
      availability continues to be low throughout most of Asia. Formulary deficiencies
      are severe in several countries, in particular Bangladesh, Myanmar, Afghanistan,
      Kazakhstan and Laos. Even when opioids are on formulary, they are often
      unavailable, particularly in the same countries. Access is significantly impaired
      by widespread over-regulation that continues to be pervasive across the region. 

PMID- 24285227
TI  - Formulary availability and regulatory barriers to accessibility of opioids for
      cancer pain in India: a report from the Global Opioid Policy Initiative (GOPI).
AB  - India is the world's largest democracy with control of opioids divided between
      the national and state governments. While the global consumption of opioids has
      increased, the consumption has not increased at the same rate. This is the first
      comprehensive study of opioid availability and accessibility for cancer patients
      in India. Data are reported on the availability and accessibility of opioids for
      the management of cancer pain in 24 of the states that make up India and the
      Administrative area around Delhi. About 1061 million of the nation's 1189 million
      people (89%) are covered by this survey. Without exception, opioid availability
      continues to be low throughout all of India. Even when opioids are on formulary,
      they are often unavailable. Access is significantly impaired by widespread over
      regulation that continues to be pervasive across the nation. 

PMID- 24285228
TI  - Formulary availability and regulatory barriers to accessibility of opioids for
      cancer pain in Latin America and the Caribbean: a report from the Global Opioid
      Policy Initiative (GOPI).
AB  - The nations of the Caribbean, Central America and South America form a
      heterogeneous region with substantial variability in economic, social and
      palliative care development. Palliative care provision is at varied stages of
      development throughout the region. The consumption of opioids in Latin America
      and the Caribbean is variable with moderate levels of consumption by
      international standards (1-10 mg morphine equivalents/capita/year) observed in
      Argentine, Brazil, Chile, Colombia, Cuba, Mexico, Costa Rica, Uruguay and most of
      the Caribbean but relatively low levels of consumption in other countries
      particularly Guatemala, Honduras and Bolivia. Data for Latin American and
      Caribbean is reported on the availability and accessibility of opioids for the
      management of cancer pain in 24 of the 33 countries surveyed. The results of this
      survey are relevant to 560 million of the region's 595 million people (94%).
      Opioid availability continues to be low throughout most of Latin America and the
      Caribbean. While formularies in this region generally include all recommended
      morphine formulations, access is significantly impaired by widespread over
      regulation that continues to be pervasive across the region. 

PMID- 24285230
TI  - Formulary availability and regulatory barriers to accessibility of opioids for
      cancer pain in the Middle East: a report from the Global Opioid Policy Initiative
      (GOPI).
AB  - The Middle East is a heterogeneous region with substantial variability in social
      development, wealth and palliative care development. The region has few
      democracies, strong but diverse religious affiliations, and many of the region's
      counties are involved in political upheavals or regional conflicts. While the
      global consumption of opioids has increased throughout the last 30 years, there
      has been little increase in opioid consumption in the Middle East. This is the
      first comprehensive study of opioid availability and accessibility of opioids in
      the Middle East. Data are reported on the availability and accessibility of
      opioids for the management of cancer pain in 16 of 24 countries. The data are
      relevant to 329 million of the region's 403 million people (82%). The survey
      found that with the exception of Israel, opioid availability continues to be low
      throughout most of the Middle East. Formulary deficiencies are severe in several
      countries in particular Afghanistan, Iraq, Lebanon, Libya, Palestine and Tunisia.
      Even when opioids are on formulary, they are often unavailable, particularly in
      these same countries. Access is also significantly impaired by widespread over
      regulation that is pervasive across the region. 

PMID- 24285231
TI  - Next steps in access and availability of opioids for the treatment of cancer
      pain: reaching the tipping point?
AB  - The reports of the Global Opioid Policy Initiative (GOPI) project to evaluate the
      availability and accessibility of opioids for the management of cancer pain in
      Africa, Asia, Latin America and the Caribbean, and the Middle East, together with
      the previous 2010 European Society for Medical Oncology (ESMO)/European
      Association for Palliative Care (EAPC) report from Europe, have provided critical
      data in demonstrating the deficiencies in many countries throughout the world.
      Formulary deficiencies and over-regulation are pandemic and must be addressed.
      This process is challenging and will require concerted and sustained efforts by
      clinical leaders and advocacy groups partnering with international and regional
      organizations and, of course, with national governments and their competent
      authorities. There is a growing international expertise and infrastructure to
      coordinate advocacy and strategic planning based on the World Health Organization
      (WHO) Model of Education, Policy Reform and Medication Availability. 

PMID- 24285233
TI  - Categories and dimensions, brain and behavior: the yins and yangs of
      psychopathology.

PMID- 24285234
TI  - Optimization of the radiosynthesis of [(18) F]MEFWAY for imaging brain serotonin
      1A receptors by using the GE TracerLab FXFN-Pro module.
AB  - The aim of this study was to develop a highly reliable radiofluorination method
      for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)
      N-(4-(18) F-fluoromethylcyclohexane)carboxamide ([(18) F]Mefway) by using a fully
      automated system. The optimal condition is composed of two parts. The extraction
      system of the trapped F-18 in the anion exchange resin (i.e., quaternary
      methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL
      methanol) and K2 CO3 (1 mg/0.1 mL H2 O). After removing the solvents, the trans
      tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222
      K[(18) F] at 100 degrees C for 5 min. After purification and formulation, [(18)
      F]Mefway was obtained with 38 +/- 2.4% (decay corrected, n = 34) radiochemical
      yield, a total synthesis time of 52 +/- 3.4 min, specific activity was 120.6 +/-
      8.7 GBq/umol at the end of synthesis and a radiochemical purity of 99%. According
      to the quality control tests, formulated [(18) F]Mefway is suitable to apply
      parenteral clinical application. 

PMID- 24285235
TI  - (-)-[(18) F]Flubatine: evaluation in rhesus monkeys and a report of the first
      fully automated radiosynthesis validated for clinical use.
AB  - (-)-[(18) F]Flubatine was selected for clinical imaging of alpha4 beta2 nicotinic
      acetylcholine receptors because of its high affinity and appropriate kinetic
      profile. A fully automated synthesis of (-)-[(18) F]flubatine as a sterile
      isotonic solution suitable for clinical use is reported, as well as the first
      evaluation in nonhuman primates (rhesus macaques). (-)-[(18) F]Flubatine was
      prepared by fluorination of the Boc-protected trimethylammonium iodide precursor
      with [(18) F]fluoride in an automated synthesis module. Subsequent deprotection
      of the Boc group with 1-M HCl yielded (-)-[(18) F]flubatine, which was purified
      by semi-preparative HPLC. (-)-[(18) F]Flubatine was prepared in 25% radiochemical
      yield (formulated for clinical use at end of synthesis, n = 3), >95%
      radiochemical purity, and specific activity = 4647 Ci/mmol (171.9 GBq/umol).
      Doses met all quality control criteria confirming their suitability for clinical
      use. Evaluation of (-)-[(18) F]flubatine in rhesus macaques was performed with a
      Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain
      was imaged for 90 min, and data were reconstructed using the 3-D maximum a
      posteriori algorithm. Image analysis revealed higher uptake and slower washout in
      the thalamus than those in other areas of the brain and peak uptake at 45 min.
      Injection of 2.5 ug/kg of nifene at 60 min initiated a slow washout of [(18)
      F]flubatine, with about 25% clearance from the thalamus by the end of imaging at
      90 min.

PMID- 24285236
TI  - Synthesis of stable isotope labeled anacetrapib, its major metabolites and [(14)
      C]anacetrapib.
AB  - Cholesteryl ester transfer protein inhibitors are an important class of compounds
      designed to treat hypocholesterolemia and prevent cardiovascular disease.
      Anacetrapib (MK-0859) is currently in phase III trials for the treatment of
      elevated cholesterol levels and prevention of cardiovascular disease. In order to
      further support the development of anacetrapib, we prepared [M + 6]MK-0859, which
      was required in support of an absolute bioavailability study of the active
      pharmaceutical ingredient (API). Additional support included the synthesis of an
      internal standard [M + 13] and three stable isotope labeled metabolites, which
      were used to analyze clinical samples, and [(14) C]MK-0859 to support drug
      metabolism studies. 

PMID- 24285237
TI  - Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands
      for selective imaging of dopamine D4 receptors.
AB  - The D(4) receptor is of high interest for research and clinical application but
      puts high demands on appropriate radioligands to be useful tools for
      investigation. Search for adequate radioligands suitable for in vivo imaging is
      therefore still in progress. The potential neuroleptic drug 6-(4-[4
      fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to
      the D(4) receptor. Derivatization of this lead structure by adding hydrophilic
      moieties was carried out in order to lower its lipophilicity what led to three
      new putative dopamine receptor D(4) ligands. A comprehensive description of the
      syntheses of standard compounds and corresponding labeling precursors is given
      which were obtained in satisfactory yields. Furthermore, the radiosyntheses by
      direct (18) F-labeling and build-up synthesis were compared. All derivatives of 6
      (4-[4-fluorobenzyl]-piperazin-1-yl)benzodioxin were successfully synthesized in
      (18) F-labeled form with radiochemical yields of 9-35% and molar activities of 30
      60 GBq/umol using one-pot procedures.

PMID- 24285238
TI  - Alternative synthesis for the preparation of 16alpha-[(18) F]fluoroestradiol.
AB  - We have developed a new precursor, 3,17beta-O-bis(methoxymethyl)-16beta-O-p
      nitrobenzenesulfonylestriol (14c) of 16alpha-[(18) F]fluoroestradiol ([(18)
      F]FES). Although we could not selectively protect the C17 alcohol in the presence
      of the C16 alcohol, we were able to prepare and chromatographically isolate the
      desired C16 TBDMS, C17,C3-dimethoxymethyl (diMOM) protected estriol derivative
      and convert into the ultimate fluorination precursor. The MOM protective group
      proved to be more quickly removed than the cyclic sulfate group. The di-MOM
      protective precursor at the C3 and C17 alcohols instead of a cyclic sulfate group
      shortened hydrolysis time. We prepared three different sulfonate precursors at
      C16 alcohol. After checking their reactivity in the [(18) F]fluorination step and
      considering the stability of the precursors, we obtained the best results with
      nosylate precursor 14c. 

PMID- 24285239
TI  - (99m) Tc-tricabonyl labeling of ofloxacin and its biological evaluation in
      Staphylococcus aureus as an infection imaging agent.
AB  - Even in recent decades, one of the major causes of death and unhealthiness in the
      whole world is infection and inflammation. The use of radiopharmaceuticals is a
      powerful tool in managing the patients with infectious diseases. In this study,
      ofloxacin as a second-generation fluoroquinolone has been labeled with [(99m)
      Tc(CO)3 (H2 O)3 ](+) core to formulate a suitable infection imaging agent.
      Ofloxacin was radiolabeled with (99m) Tc using carbonyl core. Radioligand
      chemical analysis involved HPLC methods. Radioconjugate stability and
      lipophilicity were determined. Binding with Staphylococcus aureus and
      biodistribution in infected mice for labeled compound were studied. The
      radioligand was characterized by HPLC, and its radiochemical purity was more than
      90%. In vitro stability studies have shown the complex was stable at least 6 h
      after labeling at room temperature. The n-octanol/water partition coefficient
      experiment exhibited logP = 1.52 +/- 0.21 for (99m) Tc(CO)3 -ofloxacin. The
      complex showed specific binding to S. aureus. Biodistribution results showed that
      radioligand had high accumulation in the infected muscle in a mice (T/NT = 2.02
      +/- 0.12 at 4 h postinjection). On the basis of stability and infection site
      uptake ratio, suitability of this complex as a radiotracer for imaging of
      infections is recognized. 

PMID- 24285240
TI  - An alternative and robust synthesis of [(13) C4 ]Baraclude(r) (entecavir).
AB  - Stable isotope-labeled [(13) C4 ]entecavir (1) was prepared in 11 steps.
      Commercially available [(13) C]guanidine hydrochloride and diethyl[1,2,3-(13) C3
      ]malonate were condensed to yield 2-amino[2,4,5,6-(13) C4 ]pyrimidine-4,6-diol
      (8). This was converted to the desired purine (7) in five steps. Introduction of
      the chiral epoxide was followed by subsequent deprotection to give [(13) C4
      ]entecavir (1), in an overall yield of 5.7% from labeled precursors. The chemical
      purity of the title compound was determined to be >99% by HPLC. The isotopic
      distribution was determined by mass spectrometry to be 282[M + 4], 98.4%; 281[M +
      3], 1.6%; and 278[M + 0], <0.1%.

PMID- 24285241
TI  - Pyridine derivatives, especially 2,6-di-tert-butylpyridine, labeled with nitrogen
      15.
AB  - Pyridine derivatives labeled with (15) N can be prepared by the reaction of the
      corresponding pyrylium salts with (15) NH4 Cl in close to a stoichiometric ratio,
      in a sodium acetate-acetic acid buffer. In particular, the reaction of 2,6-di
      tert-butylpyrylium perchlorate gave 2,6-di-tert-butylpyridine with a conversion
      of 95%. The compound is valuable for studies of acid-base interactions on solid
      acid catalysts by (15) N nuclear magnetic resonance. 

PMID- 24285243
TI  - Drug resistance: making a point.

PMID- 24285244
TI  - Intravital biobank and personalized cancer therapy: the correlation with omics.
AB  - Biobanks have played a decisive role in all aspects of the field of cancer,
      including pathogenesis, diagnosis, prognosis and treatment. The significance of
      cancer biobanks is epitomized through the appropriate application of various "
      omic" techniques (omics). The mutually motivated relationship between biobanks
      and omics has intensified the development of cancer research. Human cancer
      tissues that are maintained in intravital biobanks (or living tissue banks)
      retain native tumor microenvironment, tissue architecture, hormone responsiveness
      and cell-to-cell signalling properties. Intravital biobanks replicate the
      structural complexity and heterogeneity of human cancers, making them an ideal
      platform for preclinical studies. The application of omics with intravital
      biobanks renders them more active, which makes it possible for the cancer-related
      evaluations to be dynamically monitored on a real-time basis. Integrating
      intravital biobank and modern omics will provide a useful tool for the discovery
      and development of new drugs or novel therapeutic strategies. More importantly,
      intravital biobanks may play an essential role in the creation of meaningful
      patient-tailored therapies as for personalized medicine. 

PMID- 24285245
TI  - Current knowledge and trends in age-related macular degeneration: genetics,
      epidemiology, and prevention.
AB  - PURPOSE: To address the most dynamic and current issues concerning human
      genetics, risk factors, pharmacoeconomics, and prevention regarding age-related
      macular degeneration. METHODS: An online review of the database Pubmed and Ovid
      was performed, searching for the key words: age-related macular degeneration,
      AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their
      compound phrases. The search was limited to articles published since 1985 to
      date. All returned articles were carefully screened and their references were
      manually reviewed for additional relevant data. The webpage
      www.clinicaltrials.gov was also accessed in search of relevant research trials.
      RESULTS: A total of 366 articles were reviewed, including 64 additional articles
      extracted from the references and 25 webpages and online databases from different
      institutions. At the end, only 244 references were included in this review.
      CONCLUSION: Age-related macular degeneration is a complex multifactorial disease
      that has an uneven manifestation around the world but with one common
      denominator, it is increasing and spreading. The economic burden that this
      disease poses in developed nations will increase in the coming years. Effective
      preventive therapies need to be developed in the near future.

PMID- 24285246
TI  - Diagnostic and therapeutic challenges.

PMID- 24285247
TI  - Christianson syndrome: spectrum of neuroimaging findings.
AB  - Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized
      by severe intellectual disability, absent speech, microcephaly, ataxia, seizures,
      and behavioral abnormalities. The clinical phenotypes of CS and Angelman syndrome
      (AS) are similar. Differentiation between CS and AS is important in terms of
      genetic counseling. We report on two children with CS and confirmed mutations in
      SLC9A6 focusing on neuroimaging findings and review the available literature.
      Cerebellar atrophy (CA) occurs in approximately 60% of the patients with CS and
      develops after the age of 12 months. Hyperintense signal of the cerebellar cortex
      (CbC) is less common, and may be diffuse, patchy, or involve only the inferior
      part of the cerebellum and is best seen on coronal fluid attenuation inversion
      recovery images. CA and CbC-hyperintensity are not neuroimaging features of AS.
      In a child with the phenotype of AS, CA and/or CbC-hyperintensity are rather
      specific for CS and should prioritize sequencing of SLC9A6. 

PMID- 24285248
TI  - Troubling "environments": postgenomics, Bajan wheezing, and Levi-Strauss.
AB  - Postgenomics is intended to move beyond the search for genes to explore disease
      as a result of genes interacting with their environment, revealing how they have
      relevance for health. This addition of environment confers genomic research with
      new cultural life, making it relevant to public health discourse, government
      interventions, and health disparities. Drawing on ethnographic research following
      an American genetics of asthma study conducted in Barbados, I explore the ways
      environment gets construed by the multiple communities involved-U.S. researchers,
      Bajan officials, medical practitioners, and patient participants. I draw on Levi
      Strauss to argue that plural competing environments give mana to the American
      postgenomic project as intervention on racial injustice, household practices,
      pollution, and other aspects of asthma. 

PMID- 24285249
TI  - Differential regulation of atrial contraction by P1 and P2 purinoceptors in
      normotensive and spontaneously hypertensive rats.
AB  - In the normotensive rat atrium, adenosine-5'-triphosphate and uridine-5'
      triphosphate exert a biphasic effect consisting of an initial negative inotropic
      effect (NIE) followed by a subsequent positive inotropic effect (PIE). We
      comparatively studied these responses in normotensive Wistar rats (NWRs) and
      spontaneously hypertensive rats (SHRs). Compared with NWRs, the NIE responses in
      the atria were lower and the PIE responses were higher in SHRs. The P1
      purinoceptor antagonist, D 8-cyclopentyl-1,3-dipropylxanthine, partially blocked
      the NIE responses of both ATP and UTP and mildly enhanced the PIE responses in
      both NWRs and SHRs. Furthermore, the P2 purinoceptor blockers suramin and
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt induced a
      pronounced block of the PIE responses in both atria types. The PIE responses to
      ATP were inhibited more efficiently by nifedipine. These responses were depressed
      by ryanodine and, to a lesser extent, carbonyl cyanide 3-chlorophenylhydrazone in
      SHR atria compared with NWR atria. The higher responses in SHR rats suggest the
      existence of an augmented endoplasmic reticulum Ca(2+) store and faster
      mitochondrial Ca(2+) cycling in SHR atria compared with NWR atria. These data
      support the hypothesis that a dysfunction of purinergic neurotransmission and
      enhanced sympathetic activity are contributing factors in the pathogenesis of
      hypertension. 

PMID- 24285250
TI  - Epidemiology of interruptions to nutrition support in critically ill children in
      the pediatric intensive care unit.
AB  - BACKGROUND: Nutrition support is often delayed or interrupted. The aim of this
      study is to identify reasons for and quantify time spent without nutrition in a
      mixed medical-surgical-cardiac pediatric intensive care unit (PICU). METHODS:
      Data were prospectively collected to describe the patient cohort (anthropometrics
      and diagnostic category) and nutrition practices (time to nutrition initiation;
      frequency, duration, and causes of interruptions; and overall caloric intake).
      Descriptive statistics were used; comparisons of groups were performed using an
      independent t test and P < .05 as significance. RESULTS: The mean (standard
      deviation) time to nutrition initiation was 22.8 (16.6) hours following
      admission; 35% of patients were initiated after >24 hours. Nutrition was
      interrupted 1.2 (2.0) times per patient. Time spent without nutrition due to
      interruptions was 11.6 (23.0) hours, up to 102 hours. Patients spent 42.4%
      (28.2%) of their median (range) PICU admission of 2.9 days (0.25-39 days) without
      any form of nutrition. Patients aged 0-6 months had a significantly higher mean
      number and duration of interruptions (P = .001 and P < .001, respectively)
      compared with children >6 months. Interruptions due to surgery and planned
      extubation lasted significantly longer than all other interruptions (P < .001 and
      P = .001, respectively). Pediatric Risk of Mortality (PRISM) III scores were not
      correlated with percentage of length of stay spent without nutrition (r = 0.137).
      CONCLUSIONS: Prolonged time to nutrition initiation and interruptions in delivery
      caused pediatric patients to spend a high proportion of admission without
      nutrition support, preventing most from meeting energy requirements. Further
      research addressing specific patient outcomes is required to define optimal
      initiation times and appropriate procedural-specific fasting times.

PMID- 24285253
TI  - BaRh2Si9--a new clathrate with a rhodium-silicon framework.
AB  - The semiconducting compound BaRh2Si9 is a new kind of intermetallic clathrate. It
      was obtained by reacting BaSi, Rh and Si at 950  degrees C. The crystal structure
      (space group C2/c; Pearson symbol mC48, a = 6.2221(5) A, b = 21.399(2) A, c =
      6.2272(5) A, beta = 90.306(7) degrees ) displays a covalently bonded Rh-Si
      framework, in which four-connected Si atoms partly show unusually small bond
      angles. The Ba atoms are encapsulated in large polyhedral cages formed by 18 Si
      and 4 Rh atoms. The compound is a diamagnetic p-type semiconductor, which is in
      agreement with band structure calculations resulting in a band gap of 0.12 eV.
      Quantum chemical calculations reveal positively charged Ba atoms (Ba(+1.3)) and
      negatively charged Rh atoms (Rh(-1)). Si atoms with neighboring Rh atoms are
      positively charged, while those connected only with Si atoms are negatively
      charged. 

PMID- 24285251
TI  - Randomized clinical trial of new intravenous lipid (SMOFlipid 20%) versus medium
      chain triglycerides/long-chain triglycerides in adult patients undergoing
      gastrointestinal surgery.
AB  - BACKGROUND: SMOFlipid 20% is intravenous lipid emulsion (ILE) containing long
      chain triglycerides (LCT), medium-chain triglycerides (MCT), olive oil, and fish
      oil as a mixed emulsion containing alpha-tocopherol. The aim was to assess the
      efficacy of this new ILE in gastrointestinal surgery compared with MCT/LCT.
      METHODS: In this prospective study, 40 patients were randomized to SMOFlipid 20%
      or MCT/LCT (Lipovenoes 20%) group. Clinical and biochemistry data were collected.
      Inflammatory markers (CRP, IL-6, IL-10, TNF-alpha, TGF-beta1) and oxidative
      stress (ROS and superoxide) were measured. RESULTS: Thirty-five patients (17
      males and 18 females) with a mean age of 57 years completed the study. The
      patients' demographic characteristics (age, gender, height, body weight, and BMI)
      were similar without significant differences between groups. The increment of
      triglyceride on day 6 from baseline was significantly lower in SMOFlipid group
      than in Lipovenoes MCT/LCT group. Inflammatory markers, as well as superoxide
      radical and total oxygen radical were not different between groups. CONCLUSIONS:
      Despite the comparable effect on inflammatory response, because of its well
      balanced fatty acid pattern, relatively low n-6:n-3 ratio, and high vitamin E
      content, SMOFlipid had a better triglyceride-lowering effect as compared with
      MCT/LCT in adult patients undergoing gastrointestinal surgery.

PMID- 24285255
TI  - Enhanced detection efficiency of direct conversion X-ray detector using polyimide
      as hole-blocking layer.
AB  - In this article we demonstrate the performance of a direct conversion amorphous
      selenium (a-Se) X-ray detector using biphenyldisnhydride/1,4 phenylenediamine
      (BPDA/PPD) polyimide (PI) as a hole-blocking layer. The use of a PI layer with a
      Se allows detector operation at high electric fields (>=10 V/MUm) while
      maintaining low dark current, without deterioration of transient performance. The
      hole mobility of the PI/a-Se device is measured by the time-of-flight method at
      different electric fields to investigate the effect of the PI layer on detector
      performance. It was found that hole mobility as high as 0.75 cm(2)/Vs is
      achievable by increasing the electric field in the PI/a-Se device structure.
      Avalanche multiplication is also shown to be achievable when using PI as a
      blocking layer. Increasing the electric field within a-Se reduces the X-ray
      ionization energy, increases hole mobility, and improves the dynamic range and
      sensitivity of the detector.

PMID- 24285252
TI  - Sinodielide A exerts thermosensitizing effects and induces apoptosis and G2/M
      cell cycle arrest in DU145 human prostate cancer cells via the Ras/Raf/MAPK and
      PI3K/Akt signaling pathways.
AB  - Sinodielide A (SA) is a naturally occurring guaianolide, which is isolated from
      the root of Sinodielsia yunnanensis. This root, commonly found in Yunnan
      province, is used in traditional Chinese medicine as an antipyretic, analgesic
      and diaphoretic agent. A number of studies have reported that agents isolated
      from a species of Umbelliferae (Apiaceae) have antitumor activities. We
      previously reported, using combined treatments with this medicinal herb and
      hyperthermia at various temperatures, an enhanced cytotoxicity in the human
      prostate cancer androgen-independent cell lines, PC3 and DU145, and analyzed the
      related mechanisms. In the present study, we investigated the effects of
      treatment with SA prior to hyperthermia on the thermosensitivity of DU145 cells,
      and the mechanisms related to the induction of apoptosis and G(2)/M cell cycle
      arrest via the activation of extracellular-regulated kinase (ERK)1/2, c-Jun N
      terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways,
      as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. Cells
      were exposed to hyperthermia alone (40-44C) or hyperthermia in combination with
      SA. Lethal damage to cells treated with mild hyperthermia (40 or 42C) for up to 6
      h was slight; however, hyperthermia in combination with SA synergistically
      enhanced thermosensivity. Lethal damage to cells treated with acute hyperthermia
      (43 or 44C) was more severe, but these effects were also enhanced and were more
      significant by the combined treatment with SA. The kinetics of apoptosis
      induction and cell cycle distribution were analyzed by flow cytometry. In
      addition, the levels of ERK1/2, JNK and Akt were determined by western blot
      analysis. The incidence of apoptotic cells after treatment with SA (20.0 uM) at
      37C for 4 h, hyperthermia (44C) alone for 30 min, and the combination in sequence
      were examined. The sub-G1 division (%) in the diagram obtained by flow cytometry
      was applied to that assay. The percentage of apoptotic cells (10.53+/-5.02%) was
      higher at 48 h as compared to 0, 12 and 24 h after treatment. The distribution of
      DU145 cells in the G2/M cell cycle phase was markedly increased after 24 h of
      heating at 44C and after the combined treatment with heating and SA. The
      phosphorylation of ERK1/2 was reduced following treatment with heating and SA,
      while the levels of phosphorylated JNK (p-JNK) were markedly increased
      immediately after heating at 44C and when heating was combined with SA. By
      contrast, the levels of phosphorylated Akt (p-Akt) were immediately increased
      only after heating at 44C. Thus, we concluded that SA exerts its
      thermosensitizing effects on DU145 cells by inhibiting the activation of the
      MAPK/ERK1/2 and PI3K/Akt signaling pathways.

PMID- 24285256
TI  - ABCB1 haplotype influences the sirolimus dose requirements in Chinese renal
      transplant recipients.
AB  - Sirolimus, an immunosuppressive drug used to prevent organ rejection after renal
      transplantation, has a narrow therapeutic index and a large inter-individual
      variability of pharmacokinetics. The aim of this study was to analyse the dose
      normalized trough blood concentrations (C0 /D ratio) of sirolimus in patients
      with different genotypes and attempt to investigate the possible associations
      between ABCB1/CYP3A5 genotypes and sirolimus dose requirements in Chinese renal
      transplant recipients. Blood samples were collected from 85 Chinese renal
      transplant recipients who were treated with sirolimus for at least 3 months and
      polymorphisms of the ABCB1 and CYP3A5 were determined by the SNaPShot multiplex
      assay. The blood concentrations of sirolimus were determined with HPLC. A
      significant allele-dependent effect was observed between the CYP3A5*3
      polymorphism and the C0 /D ratio of sirolimus. The patients bearing at least one
      CYP3A5*1 allele had a lower sirolimus C0/D ratio compared with those with a
      homozygous CYP3A5*3 genotype (p < 0.05). No significant differences of sirolimus
      C0/D ratios were observed among various ABCB1 1236C>T, 2677G>T/A and 3435C>T
      genotype groups. However, haplotype analysis including ABCB1 1236C>T, 2677G>T/A
      and 3435C>T SNPs showed that the mean sirolimus C0/D of subjects carrying the
      CGC/CGC diplotype was about 30% lower compared with those carrying the CGC/TTT or
      TTT/TTT diplotype, whether or not they expressed the CYP3A5 (p < 0.05). These
      results demonstrated that the haplotype of ABCB1 might be a better index for the
      prediction of sirolimus blood concentration than single SNPs. Genotyping of ABCB1
      and CYP3A5 might help to optimize individualized sirolimus treatments for Chinese
      renal transplant recipients.

PMID- 24285258
TI  - The mechanisms for the high resistance to sulfur poisoning of the Ni/yttria
      stabilized zirconia system treated with Sn vapor.
AB  - The mechanisms for the resistance to sulfur poisoning at the triple phase
      boundary (TPB) of the Ni/yttria-stabilized zirconia (YSZ) system treated with Sn
      vapor are studied using the first-principles method based on density functional
      theory. Models with Sn dopant or adsorbate are proposed. It is found that the TPB
      model of the Ni/YSZ system with Sn dopant in Ni can to some extent restrain the
      diffusion of sulfur from the Ni part to the interface O vacancy by forcing the
      sulfur atom to diffuse along a longer path, which increases the time for which
      sulfur remains at the Sn doped Ni surface and allows the O ion to diffuse to the
      O vacancy at the interface. Once the O ion diffuses to the O vacancy, it forms
      interface O(2-), which repels the sulfur adsorbate and eliminates the sulfur
      poisoning. However, as the barriers of sulfur diffusion to the vacancy are still
      small (0.25 eV or smaller), the Sn dopant in Ni does not efficiently eliminate
      the sulfur poisoning at the TPB. In contrast, the TPB model of the Ni/YSZ system
      with an Sn adatom on the Ni can form a physical barrier and prevent effectively
      sulfur diffusion to the O vacancy at the interface. The diffusion barriers are as
      large as 1.41 eV, which therefore eliminates the sulfur poisoning at the TPB. The
      results give a detailed dynamic picture of the mechanism of the high tolerance to
      sulfur poisoning of the Ni/YSZ anode at the TPB after the pre-exposures to
      metallic tin vapor. 

PMID- 24285257
TI  - Update on selective treatments targeting neutrophilic inflammation in
      atherogenesis and atherothrombosis.
AB  - Atherosclerosis is the most common pathological process underlying cardiovascular
      diseases. Current therapies are largely focused on alleviating hyperlipidaemia
      and preventing thrombotic complications, but do not completely eliminate risk of
      suffering recurrent acute ischaemic events. Specifically targeting the
      inflammatory processes may help to reduce this residual risk of major adverse
      cardiovascular events in atherosclerotic patients. The involvement of neutrophils
      in the pathophysiology of atherosclerosis is an emerging field, where evidence
      for their causal contribution during various stages of atherosclerosis is
      accumulating. Therefore, the identification of neutrophils as a potential
      therapeutic target may offer new therapeutic perspective to reduce the current
      atherosclerotic burden. This narrative review highlights the expanding role of
      neutrophils in atherogenesis and discusses on the potential treatment targeting
      neutrophil-related inflammation and associated atherosclerotic plaque
      vulnerability. 

PMID- 24285259
TI  - Valence state, hybridization and electronic band structure in the charge ordered
      AlV2O4.
AB  - The valence state, hybridization and electronic band structure of charge ordered
      AlV2O4 are investigated by measuring the electron energy loss spectra (EELS) and
      performing band structure calculations using the WIEN2k code. White line ratio
      and O K edges of V2O5, VO2, V2O3 and AlV2O4, obtained using electron energy loss
      spectroscopy, are analysed specifically to probe systematically the VO6 octahedra
      in all of them. The systematic decrease of the L2 intensity and the O K edge
      intensity from V(5+) in V2O5 to AlV2O4 indicates a progressive increase in the
      occupancy of the hybridized states, which is corroborated by the absence of a
      transition from O 1s to hybridized 2t(2g). Band structure calculations on the
      parent charge frustrated cubic phase and the charge ordered rhombohedral phase
      clearly document a band gap in the charge ordered state. From the structural
      information obtained after convergence and the spectroscopic information from
      EELS, it appears that partial orbital occupancy may lead to a deviation from an
      integral valence state on all the vanadium in this exotic charge ordered spinel
      system.

PMID- 24285260
TI  - Association between the CHADS2 score and an ankle-brachial index of <0.9 in
      patients without atrial fibrillation.
AB  - AIM: The ankle-brachial index(ABI) is an easy-to-use, non-invasive and reliable
      diagnostic tool for assessing peripheral arterial occlusive disease(PAOD). The
      CHADS2(congestive heart failure, hypertension, age ?75 years, diabetes, prior
      stroke) score is a simple and popular clinical parameter that is used to assess
      the risk of stroke in patients with atrial fibrillation (AF). Because all five
      components of the CHADS2 score are risk factors for PAOD, the score should have a
      strong correlation with the presence of PAOD. However, there are limited studies
      regarding the association between the CHADS2 score and PAOD in patients without
      AF. Therefore, the aim of the present study was to investigate whether the CHADS2
      score is positively associated with PAOD in patients without AF. METHODS: A total
      of 1,320 patients without AF were included in this study. The ABI was measured
      using an ABI-form device. PAOD was defined as an ABI of <0.9 in either leg.
      RESULTS: Among the 1,320 subjects (mean age: 60.3+/-13.4 years), the prevalence
      of an ABI of <0.9 was 5.7%. A multivariate analysis showed that an increased
      age(odds ratio [OR], 1.054; p<0.001), decreased estimated glomerular filtration
      rate (OR, 0.971; p<0.001) and increased CHADS2 score (OR, 1.861; p<0.001) were
      independently associated with an ABI of <0.9. CONCLUSIONS: Our study demonstrated
      that the CHADS2 score is significantly associated with an ABI of <0.9 in non-AF
      patients. Further prospective studies are needed to examine the ability of the
      CHADS2 score to predict the incidence of PAOD.

PMID- 24285261
TI  - New strategies in treating male lower urinary tract symptoms.
AB  - PURPOSE OF REVIEW: Improved understanding of the pathogenesis of lower urinary
      tract symptoms (LUTS) has led to the development of new drugs to treat male LUTS.
      The review aims to give an overview to the new drugs and to compounds in the
      pipeline. RECENT FINDINGS: Tadalafil, a phosphodiesterase type 5 inhibitor, is a
      drug newly approved for the treatment of male LUTS and a true new challenger for
      the current standard treatment with alpha1 blockers, particularly in men with
      concomitant erectile dysfunction. Botulinum toxin and mirabegron, a beta3
      agonist, might be of value in treating persistent storage LUTS. Intraprostatic
      injections with botulinum toxin, NX-1207, and PRX302, need further evaluation but
      might be treatment alternatives in the future. Similarly, vitamin D3 receptor
      analogues (e.g., elocalcitol), gonadotropin-releasing hormone antagonists (e.g.,
      cetorelix), and modulators of the cannabinoid system (e.g., fatty acid amide
      hydrolase inhibitors) need further evaluation in clinical studies. Other
      compounds, such as transient receptor potential vanilloid antagonists, Rho kinase
      inhibitors, purinergic receptor blockers, and endothelin targeting drugs, are
      still at experimental stages. SUMMARY: Novel drugs for the treatment of male LUTS
      have been introduced recently. Clinical practice along with further trials will
      have to prove their value, along with other compounds that are still in their
      early phase of development.

PMID- 24285263
TI  - Nanomechanical cutting of boron nitride nanotubes by atomic force microscopy.
AB  - The length of nanotubes is a critical structural parameter for the design and
      manufacture of nanotube-based material systems and devices. High-precision length
      control of nanotubes by means of mechanical cutting using a scriber has not
      materialized due to the lack of the knowledge of the appropriate cutting
      conditions and the tube failure mechanism. In this paper, we present a
      quantitative nanomechanical study of the cutting of individual boron nitride
      nanotubes (BNNTs) using atomic force microscopy (AFM) probes. In our nanotube
      cutting measurements, a nanotube standing still on a flat substrate was laterally
      scribed by an AFM tip. The tip-tube collision force deformed the tube, and
      eventually fractured the tube at the collision site by increasing the cutting
      load. The mechanical response of nanotubes during the tip-tube collision process
      and the roles of the scribing velocity and the frictional interaction on the tip
      tube collision contact in cutting nanotubes were quantitatively investigated by
      cutting double-walled BNNTs of 2.26-4.28 nm in outer diameter. The fracture
      strength of BNNTs was also quantified based on the measured collision forces and
      their structural configurations using contact mechanics theories. Our analysis
      reports fracture strengths of 9.1-15.5 GPa for the tested BNNTs. The
      nanomechanical study presented in this paper demonstrates that the AFM-based
      nanomechanical cutting technique not only enables effective control of the length
      of nanotubes with high precision, but is also promising as a new nanomechanical
      testing technique for characterizing the mechanical properties of tubular
      nanostructures.

PMID- 24285264
TI  - Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental
      and clinical bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a common and serious complication of
      premature birth, characterized by a pronounced arrest of alveolar development.
      The underlying pathophysiological mechanisms are poorly understood although
      perturbations to the maturation and remodeling of the extracellular matrix (ECM)
      are emerging as candidate disease pathomechanisms. In this study, the expression
      and regulation of three members of the lysyl hydroxylase family of ECM remodeling
      enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental
      animal model of BPD, were addressed. All three enzymes were localized to the
      septal walls in developing mouse lungs, with Plod1 also expressed in the vessel
      walls of the developing lung and Plod3 expressed uniquely at the base of
      developing septa. The expression of plod1, plod2, and plod3 was upregulated in
      the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD.
      Transforming growth factor (TGF)-beta increased plod2 mRNA levels and activated
      the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts.
      Using in vivo neutralization of TGF-beta signaling in the experimental animal
      model of BPD, TGF-beta was identified as the regulator of aberrant plod2
      expression. PLOD2 mRNA expression was also elevated in human neonates who died
      with BPD or at risk for BPD, compared with neonates matched for gestational age
      at birth or chronological age at death. These data point to potential roles for
      lysyl hydroxylases in normal lung development, as well as in perturbed late lung
      development associated with BPD. 

PMID- 24285266
TI  - Extracellular ATP mediates the late phase of neutrophil recruitment to the lung
      in murine models of acute lung injury.
AB  - Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is
      irrevocably linked to neutrophil emigration to the lung. Activation and
      recruitment of neutrophils to the lung is mostly attributable to local production
      of the chemokines. However, much of our understanding of neutrophil recruitment
      to the lung is based on studies focusing on early time points after initiation of
      injury. In this study, we sought to evaluate the extended temporal relationship
      between neutrophil chemotactic factor expression and influx of neutrophils into
      the lung after intratracheal administration of either LPS or bleomycin. In both
      models, results demonstrated two phases of neutrophil chemotactic factor
      expression; first, an early phase characterized by high levels of
      CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and
      CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by
      increases in extracellular ATP. Furthermore, we show that strategies aimed at
      either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or
      inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce
      extracellular ATP accumulation, limit vascular leakage, and effectively block the
      late, but not the early, stages of neutrophil recruitment to the lung after LPS
      instillation. In conclusion, this study illustrates that neutrophil recruitment
      to the lung is mediated by the time-dependent expression of chemotactic factors
      and suggests that novel strategies, which reduce extracellular ATP accumulation,
      may attenuate late neutrophil recruitment and limit lung injury during ALI. 

PMID- 24285267
TI  - Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin
      independent manner.
AB  - Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory
      failure associated with extensive pulmonary infiltrates. The pathological
      characterization of ALI includes injuries of alveolar epithelial cells (AECs),
      alveolar neutrophilic infiltration, and increases in proinflammatory cytokines,
      which cause destruction of the alveolar capillary barrier and subsequent
      devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal
      medicine, is widely used for the treatment of patients with gastrointestinal
      symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of
      RKT on organ inflammation and fibrosis remain unknown. We investigated the
      pharmacological potential of RKT in the treatment of ALI by using a bleomycin
      induced ALI model in mice. RKT or distilled water (DW) was given to mice daily
      starting 12 h after bleomycin administration. The RKT-treated mice showed a
      definitively higher survival rate than the DW-treated mice after injury. They
      also had smaller reductions in body weight and food intake. The amelioration of
      neutrophil alveolar infiltration, pulmonary vascular permeability, induction of
      proinflammatory cytokines, activation of the NF-kappaB pathway, apoptosis of
      AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT
      administration increased the plasma ghrelin levels in wild-type mice, and it also
      mitigated the ALI response in both ghrelin-deficient mice and growth hormone
      secretagogue receptor-deficient mice after lung injury. Our results indicate that
      RKT administration exerts protective effects against ALI by protecting the AECs
      and regulating lung inflammation independently of the ghrelin system, and they
      highlight RKT as a promising therapeutic agent for the management of this
      intractable disease. 

PMID- 24285265
TI  - Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in
      smokers.
AB  - A hallmark of cigarette smoking is a shift in the protease/antiprotease balance,
      in favor of protease activity. However, it has recently been shown that smokers
      have increased expression of a key antiprotease, secretory leukoprotease
      inhibitor (SLPI), yet the mechanisms involved in SLPI transcriptional regulation
      and functional activity of SLPI remain unclear. We examined SLPI mRNA and protein
      secretion in differentiated nasal epithelial cells (NECs) and nasal lavage fluid
      (NLF) from nonsmokers and smokers and demonstrated that SLPI expression is
      increased in NECs and NLF from smokers. Transcriptional regulation of SLPI
      expression was confirmed using SLPI promoter reporter assays followed by
      chromatin immunoprecipitation. The role of STAT1 in regulating SLPI expression
      was further elucidated using WT and stat1(-/-) mice. Our data demonstrate that
      STAT1 regulates SLPI transcription in epithelial cells and slpi protein in the
      lungs of mice. Additionally, we reveal that NECs from smokers have increased
      STAT1 mRNA/protein expression. Finally, we demonstrate that SLPI contained in the
      nasal mucosa of smokers is proteolytically cleaved but retains functional
      activity against neutrophil elastase. These results demonstrate that smoking
      enhances expression of SLPI in NECs in vitro and in vivo, and that this response
      is regulated by STAT1. In addition, despite posttranslational cleavage of SLPI,
      antiprotease activity against neutrophil elastase is enhanced in smokers.
      Together, our findings show that SLPI regulation and activity is altered in the
      nasal mucosa of smokers, which could have broad implications in the context of
      respiratory inflammation and infection. 

PMID- 24285268
TI  - Joseph Priestley, oxygen, and the enlightenment.
AB  - Joseph Priestley (1733-1804) was the first person to report the discovery of
      oxygen and describe some of its extraordinary properties. As such he merits a
      special place in the history of respiratory physiology. In addition his
      descriptions in elegant 18th-century English were particularly arresting, and
      rereading them never fails to give a special pleasure. The gas was actually first
      prepared by Scheele (1742-1786) but his report was delayed. Lavoisier (1743-1794)
      repeated Priestley's initial experiment and went on to describe the true nature
      of oxygen that had eluded Priestley, who never abandoned the erroneous phlogiston
      theory. In addition to oxygen, Priestley isolated and characterized seven other
      gases. However, most of his writings were in theology because he was a
      conscientious clergyman all his life. Priestley was a product of the
      Enlightenment and argued that all beliefs should be able to stand the scientific
      scrutiny of experimental investigations. As a result his extreme liberal views
      were severely criticized by the established Church of England. In addition he was
      a supporter of both the French and American Revolutions. Ultimately his political
      and religious attitudes provoked a riot during which his home and his scientific
      equipment were destroyed. He therefore emigrated to America in 1794 where his
      friends included Thomas Jefferson and Benjamin Franklin. He settled in
      Northumberland, Pennsylvania although his scientific work never recovered from
      his forced departure. But the descriptions of his experiments with oxygen will
      always remain a high point in the history of respiratory physiology.

PMID- 24285270
TI  - [The Christmas mystery of the PPMP : who was it ?].

PMID- 24285269
TI  - Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of
      asthma.
AB  - Lung mastocytosis and antigen-induced bronchoconstriction are common features in
      allergic asthmatics. It is therefore important that animal models of asthma show
      similar features of mast cell inflammation and reactivity to inhaled allergen. We
      hypothesized that house dust mite (HDM) would induce mastocytosis in the lung and
      that inhalation of HDM would trigger bronchoconstriction. Mice were sensitized
      with intranasal HDM extract, and the acute response to nebulized HDM or the mast
      cell degranulating compound 48/80 was measured with respiratory input impedance.
      Using the constant-phase model we calculated Newtonian resistance (Rn) reflecting
      the conducting airways, tissue dampening (G), and lung elastance (H).
      Bronchoalveolar lavage fluid was analyzed for mouse mast cell protease-1 (mMCP
      1). Lung tissue was analyzed for cytokines, histamine, and alpha-smooth muscle
      actin (alpha-SMA), and histological slides were stained for mast cells. HDM
      significantly increased Rn but H and G remained unchanged. HDM significantly
      expanded mast cells compared with control mice; at the same time mMCP-1, alpha
      SMA, Th2 cytokines, and histamine were significantly increased. Compound 48/80
      inhalation caused bronchoconstriction and mMCP-1 elevation similarly to HDM
      inhalation. Bronchoconstriction was eliminated in mast cell-deficient mice. We
      found that antigen-induced acute bronchoconstriction has a distinct phenotype in
      mice. HDM sensitization caused lung mastocytosis, and we conclude that inhalation
      of HDM caused degranulation of mast cells leading to an acute bronchoconstriction
      without affecting the lung periphery and that mast cell-derived mediators are
      responsible for the development of the HDM-induced bronchoconstriction in this
      model. 

PMID- 24285271
TI  - [Prevention of mental disorders].
AB  - Investment in prevention is a major public health requirement. Mental disorders
      are common and are associated with severe consequences. They are a major target
      for prevention. Based on vulnerabilitiy-stress-models the theoretical background
      for prevention in mental disorders is outlined. Effective strategies for
      children, adolescents, adults and individuals in old age do exist. Results
      regarding the prevention of depres-sion and psychoses are outlined and risk
      groups which require current actions are determined. Current activities towards a
      national prevention strategy in Germany are discussed. 

PMID- 24285272
TI  - [Interaction hypothesis examination using multiple linear regression analysis].

PMID- 24285273
TI  - [Technology in psychotherapy].

PMID- 24285274
TI  - Fusionless instrumentation in growing spine and adjacent segment problems: an
      experimental study in immature pigs.
AB  - STUDY DESIGN: Experimental study. OBJECTIVE: To compare the effects of fusionless
      instrumentation (FI) and instrumented fusion (IF) on the adjacent segment in an
      immature pig model. SUMMARY OF BACKGROUND DATA: Observations reveal proximal
      junctional kyphosis after FI. Possible reasons are stress concentration, repeated
      distractive forces, and/or soft tissue damage done in the index surgery. It was
      speculated that FI can decrease stressors to the junctional area by preserving
      the spinal mobility in some manner; however, this has not been proven to date.
      METHODS: Thirteen piglets of 10- to 14-week age were used. FI and IF were
      performed on 7 and 3 piglets, respectively, and 3 piglets formed the control
      group. Control piglets did not undergo any surgical procedures. T11-L4
      instrumentation, decortication, and grafting were applied to IF piglets. In FI
      groups, however, L1-L2 was left uninstrumented and unfused using T11-T12 and L3
      L4 levels as anchors to the growing construct. A total of 4 lengthening
      procedures were performed: 1 in the index operation and 3 more, once in each
      lengthening procedure monthly, for 3 months. Four months after the index
      operations, all piglets were killed and the adjacent segment motion capabilities,
      disc, and facets were evaluated with radiographical, magnetic resonance imaging,
      biomechanical, and histological analyses. RESULTS: Comparison of proximal
      junctional Cobb angles of the postindex (mean: 21, range: 17-27) and
      presacrification (mean: 21, range: 11-31) radiographs in the FI group revealed no
      difference (P> 0.05). In magnetic resonance imaging, both surgical group proximal
      adjacent discs showed degeneration to some degree that was statistically
      indifferent (P = 0.903). Biomechanical evaluation revealed restriction of
      adjacent segment motion in all directions for both groups; however, this negative
      effect was significantly less in FI group (P < 0.01). Degeneration observed in
      histological evaluation in adjacent discs and facets of FI group was
      significantly lower (P = 0.00). CONCLUSION: In this quadruped straight spine
      model, in comparison with IF applications, FI is closer to normal physiology even
      after several lengthening procedures regarding the adjacent segment discs, facet
      joints, and motion, when interpreting the radiological, biomechanical, and
      histological results altogether.

PMID- 24285275
TI  - Comparison of perioperative outcomes and cost of spinal fusion for cervical
      trauma: weekday versus weekend admissions.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To characterize the
      impact of the admission day (weekday vs. weekend) on the length of stay, costs,
      complications, and mortality in patients undergoing cervical spine surgery for
      spinal trauma. SUMMARY OF BACKGROUND DATA: The effect of the admission day on the
      hospital outcomes for patients undergoing anterior cervical fusion (ACF),
      posterior cervical fusion (PCF), or anterior and posterior cervical fusion (APCF)
      to manage cervical spine trauma remains unknown. METHODS: The Nationwide
      Inpatient Sample was queried from 2002 to 2011. Patients undergoing an ACF, PCF,
      or APCF for the treatment of cervical spine trauma were identified. Patients were
      separated into cohorts based on the day of admission (weekday vs. weekend).
      Patient demographics, comorbidities, admission status, length of stay, costs,
      mortality, and outcomes were assessed. A value of P <= 0.001 denoted statistical
      significance due to the large sample size. RESULTS: A total of 34,122 patients
      underwent cervical fusion for cervical spine trauma between 2002 and 2011.
      Weekend admits accounted for 11.5% (n = 3126), 19.9% (n = 1048), and 17.2% (n =
      301) of the ACF, PCF, and APCF procedures, respectively. On average, the weekend
      admits in all surgical approaches were younger, had a predilection toward more
      males, and demonstrated fewer comorbidities than the weekday cohort. ACF-treated
      weekend admits were hospitalized 4.4 days longer (P = 0.00001) and incurred
      $10,045 more in total hospital costs than the ACF-treated weekday admits (P =
      0.0003). PCF-treated weekend admits were hospitalized 2.6 days longer (P =
      0.0003) and incurred $10,227 more in total hospital costs (P = 0.0005). Finally,
      the APCF-treated weekend admits were hospitalized 4.2 days longer (P = 0.0004)
      and incurred $11,301 more in total hospital costs (P = 0.0001). The mortality
      rates were not significantly different among the admission-day cohorts. The ACF
      treated weekend cohort demonstrated significantly greater incidences of
      postoperative infection (P = 0.0003), cardiac complications (P = 0.0004), and
      urinary tract infection (P = 0.0001) than their weekday admit counterparts.
      CONCLUSION: The weekend cohorts in all surgical approaches incurred a greater
      length of stay and total hospital costs than their weekday counterparts. The ACF
      treated weekend cohort demonstrated significantly greater incidences of
      postoperative infection, cardiac complications, and urinary tract infection.
      There were no significant differences in mortality based on the admission day for
      any surgical approach. Further research is warranted to further evaluate hospital
      utilization, costs, and patient outcomes based on the admission day.

PMID- 24285276
TI  - Natural history and risk factors for adjacent vertebral fractures in the fracture
      intervention trial.
AB  - STUDY DESIGN: Retrospective analysis of prospectively collected follow-up data
      for 2.9 years. OBJECTIVE: To determine the natural history of subsequent
      morphometric fracture rates at adjacent levels (one level above or below a
      previous known baseline fracture) in a large patient database. SUMMARY OF
      BACKGROUND DATA: The long-term risk and risk factors for adjacent-level vertebral
      fractures in patients with osteoporosis are unknown. METHODS: The fracture
      intervention trial is a large randomized, placebo-controlled trial of alendronate
      treatment for osteoporosis. Data from both bisphosphonate-treated and
      bisphosphonate-naive patients (N = 1950, vertebral fracture arm) was analyzed to
      detect incident morphometric fracture rates. RESULTS: During a mean follow-up of
      2.9 years, 3.4% of patients in the alendronate group and 7.4% in the placebo
      group experienced adjacent-level vertebral fractures. The annual rate of adjacent
      level vertebral fractures was 1.2% in the alendronate group, and 2.5% in the
      placebo group (overall, 1.8% per year in both groups combined). As expected, the
      thoracolumbar region (defined as T11, T12, and L1) seemed to be the most prone to
      new adjacent-level fractures. Among females with baseline prevalent fractures at
      the thoracolumbar junction, who subsequently experienced at least one new
      fracture anywhere along the spine (N = 124), 40.3% had a new adjacent-level
      fracture in this region. Older age at randomization, lower bone mineral density,
      inactivity, and placebo therapy were significantly associated with the
      development of adjacent-level fractures in univariate analysis (P <= 0.05).
      Multivariate analysis indicated decreased odds of adjacent-level fractures with
      bisphosphonate therapy and higher bone mineral density, and increased odds with
      older age at randomization (P <= 0.05). CONCLUSION: New vertebral fractures
      adjacent to prevalent fractures occurred relatively infrequently in this
      treatment trial of alendronate in females with osteoporosis, and were more common
      with older age at randomization, lower bone mineral density and placebo
      treatment.

PMID- 24285278
TI  - A gendered users' perspective on decentralized primary health services in rural
      Tanzania.
AB  - Since the 1990s, Tanzania has been implementing health sector reforms including
      decentralization of primary healthcare services to districts and users. The
      impact of the reforms on the access, quality and appropriateness of primary
      healthcare services from the viewpoint of users is, however, not clearly
      documented. This article draws on a gendered users' perspective to address the
      question of whether the delivery of gender-sensitive primary health services has
      improved after the reforms. The article is based on empirical data collected
      through a household survey, interviews, focus group discussions, case studies and
      analysis of secondary data in two rural districts in Tanzania. The analysis shows
      that the reforms have generated mixed effects: they have contributed to improving
      the availability of health facilities in some villages but have also reinforced
      inter-village inequalities. Men and women hold similar views on the perceived
      changes and appropriateness to women on a number of services. Gender inequalities
      are, however, reflected in the significantly low membership of female-headed
      households in the community health fund and their inability to pay the user fees
      and in the fact that women's reproductive and maternal health needs are as yet
      insufficiently addressed. Although over half of users are satisfied with the
      services, more women than men are dissatisfied. The reforms appear to have put
      much emphasis on building health infrastructure and less on quality issues as
      perceived by users.

PMID- 24285279
TI  - Large-scale preparation of (13) C-labeled 2-(phenylthio)acetic acid and the
      corresponding labeled sulfoxides and sulfones.
AB  - We have developed large-scale efficient procedures for the conversion of
      commercially available [(13) C]- or [(2) H3 ,(13) C]methanol and (13) CO2 or (13)
      C-labeled bromoacetic acid to 2-(phenylthio)[1,2-(13) C2 ]-, [1-(13) C]-, and [2
      (13) C]acetic acid. The resulting derivatives are versatile, chemically stable,
      and nonvolatile two-carbon labeling precursors. We have used the (13) C
      isotopomers of 2-(phenylthio)acetic acid in the synthesis of (13) C-labeled
      acrylic acid, methacrylic acid, and trans-crotonic acid. 

PMID- 24285280
TI  - A convenient method to produce [(14) C]carbon monoxide and its application to the
      radiosynthesis of [carboxyl-(14) C]celivarone, [carboxyl-(14) C]SSR149744.
AB  - [carboxyl-(14) C]Celivarone was synthesised from barium [(14) C]carbonate with
      overall radiochemical yields in the range 49-53%. The synthetic route involves
      [(14) C]carbonylation methodology, which both decreased the number of synthetic
      steps and increased the yields obtained from previous synthetic routes. 

PMID- 24285281
TI  - A practical synthesis of [(18) F]FtRGD: an angiogenesis biomarker for PET.
AB  - Integrins have become increasingly attractive targets for molecular imaging of
      angiogenesis with positron emission tomography or single-photon emission computed
      tomography, but the reliable production of radiopharmaceuticals remains
      challenging. A strategy for chemoselective labeling of the integrin ligand
      c(RGDyK) peptide-has been developed on the basis of the Cu(I)-catalyzed
      conjugation reaction. Recently, we reported a nucleophilic detagging and fluorous
      solid-phase extraction method providing an easy way to implement an approach for
      obtaining 2-[(18) F]fluoroethyl azide. In this work, we report the practical use
      of this method for the preparation of the 2-[(18) F]fluoroethyl-triazolyl
      conjugated c(RGDyK) peptide: [(18) F]FtRGD. The two-step, two-pot synthesis, HPLC
      purification, and reformulation could be readily performed with a standard
      nucleophilic radiofluorination synthesizer (GE TRACERlab FXFN ), with minimal
      modifications. [(18) F]FtRGD was obtained in a solution for injection (>500
      MBq/mL) in 10-30% nondecay-corrected radiochemical yield, excellent radiochemical
      purity (>98%), and 28 +/- 13 GBq/umol specific activity. [(18) F]FtRGD (Ki  = 54
      +/- 14 nM for alphaV beta3 and 1.7 +/- 0.2 nM for alphaV beta5 ) was evaluated in
      mice and showed good stability in vivo, good tumor-to-background ratio (1.6 +/-
      0.3 %ID/g at 1.5 h post-injection in U87-MG tumors), and rapid urinary excretion.
      Therefore, [(18) F]FtRGD proved valuable for preclinical positron emission
      tomography imaging of integrin expression. 

PMID- 24285284
TI  - Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on
      cognition, depression, somatization and erectile function in patients with
      erectile dysfunction: a double-blind, placebo-controlled study.
AB  - Phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to have
      cognitive-enhancing effects in animal models and in our previous pilot study. To
      investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on
      cognitive function, depression and somatization in patients with erectile
      dysfunction (ED), 8-week, double-blind, placebo-controlled study enrolled 60 male
      patients with ED for >= 3 months without cognitive impairment. Forty-nine
      patients completed the study. Patients were randomized to receive either daily
      low-dose udenafil 50 mg or placebo for 2 months. The International Index of
      Erectile Function-5 (IIEF-5), the Korean version of the Mini-Mental State
      Examination (K-MMSE) for general cognitive function and the Seoul
      Neuropsychological Screening Battery for comprehensive neuropsychological
      examination, the Physical Health Questionnaire-9 (PHQ-9) for depression and the
      Physical Health Questionnaire-15 (PHQ-15) for somatization were administered at
      baseline and at 2 months. The change in the mean IIEF-5 was significantly higher
      in the udenafil group than the placebo group (6.08 +/- 4.72 vs 2.20 +/- 3.50,
      P=0.008). The changes in the PHQ-9 and PHQ-15 were -2.04 +/- 3.14 and -2.17 +/-
      2.87 in the udenafil group, and 1.20 +/- 1.63 and 0.56 +/- 2.48 in the placebo
      group (both, P<0.001). The changes in the K-MMSE and Digit Span Forward were 1.25
      +/- 1.26 and 0.92 +/- 1.02 in the udenafil group, and -0.52 +/- 1.19 and -0.24 +/
      1.13 in the placebo group (both, P<0.001). However, there were no differences in
      the other neuropsychological tests. Daily dosing with a PDE5 inhibitor seems to
      improve cognitive function, depression and somatization, as well as erectile
      function, in patients with ED.

PMID- 24285285
TI  - Comparison of experimental mouse models of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is multifactorial and involves immunological,
      environmental and genetic factors. Although there are no animal models that
      effectively mimic human IBD, experimental models allow us to analyze the
      mechanisms of chronic intestinal inflammation. IBD can be induced in mice by
      dextran sulfate sodium (DSS) or by a 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      ethanol enema, which evoke immune responses and colitis. In this study, in order
      to compare the mechanisms of inflammatory response in mice, 3 distinct models of
      IBD were established: 2% TNBS-induced acute colitis, 4% DSS-induced acute colitis
      and 2% DSS-induced chronic colitis. In addition, to evaluate the effects of TNBS
      on inflammasome activation, we used caspase-1 knockout (KO) mice. Changes in both
      body weight and survival became prominent after day 1 in the 2% TNBS-induced
      colitis model, and after day 5 in the 4% DSS-induced colitis model. The TNBS- and
      DSS-treated mice, but not the caspase-1 KO mice, showed a massive bowel edema and
      disruption of epithelial cells. The level of CD11b(+)Gr-1(+) myeloid-derived
      suppressor cells (MDSCs) was increased in all tested tissues of the TNBS- and DSS
      treated groups, apart from the basal membrane (BM) in the DSS-induced colitis
      groups and the lamina propria (LP) in the DSS-induced chronic colitis group. We
      further analyzed different subsets of CD4(+) T cells in LP and found that the
      levels of interferon (IFN)gamma-secreting (IFNgamma(+)), IL-17-secreting (IL
      17(+)), but not those of IL-4-secreting (IL-4(+)) T cells increased upon
      treatment with TNBS or DSS. In addition, discrepancies between the
      histopathologies of wild-type and caspase-1 KO mice indicated that the
      pathogenesis of IBD may be associated with the inflammasome pathway responses
      mediated by caspase-1 in TNBS-induced colitis.

PMID- 24285286
TI  - Overview of the ICRP/ICRU adult reference computational phantoms and dose
      conversion coefficients for external idealised exposures.
AB  - This paper reviews the ICRP Publications 110 and 116 describing the reference
      computational phantoms and dose conversion coefficients for external exposures.
      The International Commission on Radiological Protection (ICRP) in its 2007
      Recommendations made several revisions to the methods of calculation of the
      protection quantities. In order to implement these recommendations, the DOCAL
      task group of the ICRP developed computational phantoms representing the
      reference adult male and female and then calculated a set of dose conversion
      coefficients for various types of idealised external exposures. This paper
      focuses on the dose conversion coefficients for neutrons and investigates their
      relationship with the conversion coefficients of the protection and operational
      quantities of ICRP Publication 74. Contributing factors to the differences
      between these sets of conversion coefficients are discussed in terms of the
      changes in phantoms employed and the radiation and tissue weighting factors. 

PMID- 24285287
TI  - Automatic neutron dosimetry system based on fluorescent nuclear track detector
      technology.
AB  - For the first time, the authors are describing an automatic fluorescent nuclear
      track detector (FNTD) reader for neutron dosimetry. FNTD is a luminescent
      integrating type of detector made of aluminium oxide crystals that does not
      require electronics or batteries during irradiation. Non-destructive optical
      readout of the detector is performed using a confocal laser scanning fluorescence
      imaging with near-diffraction limited resolution. The fully automatic table-top
      reader allows one to load up to 216 detectors on a tray, read their engraved IDs
      using a CCD camera and optical character recognition, scan and process
      simultaneously two types of images in fluorescent and reflected laser light
      contrast to eliminate false-positive tracks related to surface and volume crystal
      imperfections. The FNTD dosimetry system allows one to measure neutron doses from
      0.1 mSv to 20 Sv and covers neutron energies from thermal to 20 MeV. The reader
      is characterised by a robust, compact optical design, fast data processing
      electronics and user-friendly software. 

PMID- 24285288
TI  - Low frequency of TERT promoter mutations in a large cohort of gallbladder and
      gastric cancers.

PMID- 24285289
TI  - Functionally distinct tendon fascicles exhibit different creep and stress
      relaxation behaviour.
AB  - Most overuse tendinopathies are thought to be associated with repeated
      microstrain below the failure threshold, analogous to the fatigue failure that
      affects materials placed under repetitive loading. Investigating the progression
      of fatigue damage within tendons is therefore of critical importance. There are
      obvious challenges associated with the sourcing of human tendon samples for in
      vitro analysis so animal models are regularly adopted. However, data indicates
      that fatigue life varies significantly between tendons of different species and
      with different stresses in life. Positional tendons such as rat tail tendon or
      the bovine digital extensor are commonly applied in in vitro studies of tendon
      overuse, but there is no evidence to suggest their behaviour is indicative of the
      types of human tendon particularly prone to overuse injuries. In this study, the
      fatigue response of the largely positional digital extensor and the more energy
      storing deep digital flexor tendon of the bovine hoof were compared to the
      semitendinosus tendon of the human hamstring. Fascicles from each tendon type
      were subjected to either stress or strain controlled fatigue loading (cyclic
      creep or cyclic stress relaxation respectively). Gross fascicle mechanics were
      monitored after cyclic stress relaxation and the mean number of cycles to failure
      investigated with creep loading. Bovine extensor fascicles demonstrated the
      poorest fatigue response, while the energy storing human semitendinosus was the
      most fatigue resistant. Despite the superior fatigue response of the energy
      storing tendons, confocal imaging suggested a similar degree of damage in all
      three tendon types; it appears the more energy storing tendons are better able to
      withstand damage without detriment to mechanics. 

PMID- 24285290
TI  - An empirical comparison of univariate and multivariate meta-analyses for
      categorical outcomes.
AB  - Treatment effects for multiple outcomes can be meta-analyzed separately or
      jointly, but no systematic empirical comparison of the two approaches exists.
      From the Cochrane Library of Systematic Reviews, we identified 45 reviews,
      including 1473 trials and 258,675 patients, that contained two or three
      univariate meta-analyses of categorical outcomes for the same interventions that
      could also be analyzed jointly. Eligible were meta-analyses with at least seven
      trials reporting all outcomes for which the cross-classification tables were
      exactly recoverable (e.g., outcomes were mutually exclusive, or one was a subset
      of the other). This ensured known correlation structures. Outcomes in 40 reviews
      had an is-subset-of relationship, and those in 5 were mutually exclusive. We
      analyzed these data with univariate and multivariate models based on discrete and
      approximate likelihoods. Discrete models were fit in the Bayesian framework using
      slightly informative priors. The summary effects for each outcome were similar
      with univariate and multivariate meta-analyses (both using the approximate and
      discrete likelihoods); however, the multivariate model with the discrete
      likelihood gave smaller between-study variance estimates, and narrower predictive
      intervals for new studies. When differences in the summary treatment effects were
      examined, the multivariate models gave similar summary estimates but considerably
      longer (shorter) uncertainty intervals because of positive (negative) correlation
      between outcome treatment effects. It is unclear whether any of the examined
      reviews would change their overall conclusions based on multivariate versus
      univariate meta-analyses, because extra-analytical and context-specific
      considerations contribute to conclusions and, secondarily, because numerical
      differences were often modest.

PMID- 24285292
TI  - The influence of the wind in the Schmallenberg virus outbreak in Europe.
AB  - A model previously developed for the wind-borne spread by midges of bluetongue
      virus in NW Europe in 2006 is here modified and applied to the spread of
      Schmallenberg virus in 2011. The model estimates that pregnant animals were
      infected 113 days before producing malformed young, the commonest symptom of
      reported infection, and explains the spatial and temporal pattern of infection in
      70% of the 3,487 affected farms, most of which were infected by midges arriving
      through downwind movement (62% of explained infections), or a mixture of downwind
      and random movements (38% of explained infections), during the period of day
      (1600-2100 h, i.e. dusk) when these insects are known to be most active. The main
      difference with Bluetongue is the higher rate of spread of SBV, which has
      important implications for disease control.

PMID- 24285293
TI  - Mental health services for children and adolescents: challenges and
      opportunities.

PMID- 24285294
TI  - Quercetin-3-rhamnoglucoside (rutin) stimulates transport of organic anion
      compounds mediated by organic anion transporting polypeptide 2B1.
AB  - Quercetin-3-rhamnoglucoside (rutin) has a wide spectrum of biochemical and
      pharmacological activities. Rutin is absorbed mainly in its unmetabolized form.
      Organic anion transporting polypeptide (OATP) 2B1 is a major uptake transporter
      in the intestine. Thus, it is important for the prevention of adverse events to
      understand drug interactions mediated by OATP2B1 in the absorption process. This
      study assessed the effect of rutin on transport by OATP2B1. Rutin stimulated the
      uptake of estrone-3-sulfate (E-3-S), taurocholic acid (TCA), cholic acid (CA) and
      rosuvastatin by OATP2B1, but not p-coumaric acid or ferulic acid. The EC50 of
      rutin for transport by OATP2B1 was 2.32 MUm. The Km value of E-3-S for OATP2B1 in
      the presence of rutin (9.21 MUm) was almost the same as that in the absence of
      rutin (8.53 MUm). On the other hand, the Vmax of E-3-S transport by OATP2B1 in
      the presence of rutin (270 pmol/mg protein/min) was 1.2-fold higher than that in
      the absence of rutin (218 pmol/mg protein/min). Moreover, the expression level of
      OATP2B1 on the cell membrane was increased by treatment with rutin for 5 min
      without alteration of the total OATP2B1 expression level. Moreover, the increase
      in the localization of OATP2B1 at the cell surface was detected by the
      immunocytochemistry. The stimulatory effect of rutin is a little weak but may
      affect the absorption of OATP2B1 substrates, because rutin is taken daily in
      foods and its intestinal concentration would reach the stimulatory range of
      OATP2B1.

PMID- 24285295
TI  - A speciation study of sulfur(iv) in aqueous solution.
AB  - In the current work ultraviolet spectrophotometric titrations at different S(iv)
      concentrations have been globally analysed using the entire spectral dataset to
      determine the complete speciation of S(iv) in aqueous solution over a large pH
      range (from 9.6 to 1). As a result, the dimerisation constant for the formation
      of disulfite from hydrogen sulfite has been accurately determined. Further,
      protonated disulfite has been identified and quantified for the first time. In
      addition, the molar absorptivities of all S(iv) species are also reported over
      the studied wavelength range. 

PMID- 24285296
TI  - Anticoagulant effects of statins and their clinical implications.
AB  - There is evidence indicating that statins (3-hydroxy-methylglutaryl coenzyme A
      reductase inhibitors) may produce several cholesterol-independent antithrombotic
      effects. In this review, we provide an update on the current understanding of the
      interactions between statins and blood coagulation and their potential relevance
      to the prevention of venous thromboembolism (VTE). Anticoagulant properties of
      statins reported in experimental and clinical studies involve decreased tissue
      factor expression resulting in reduced thrombin generation and attenuation of pro
      coagulant reactions catalysed by thrombin, such as fibrinogen cleavage, factor V
      and factor XIII activation, as well as enhanced endothelial thrombomodulin
      expression, resulting in increased protein C activation and factor Va
      inactivation. Observational studies and one randomized trial have shown reduced
      VTE risk in subjects receiving statins, although their findings still generate
      much controversy and suggest that the most potent statin rosuvastatin exerts the
      largest effect. 

PMID- 24285297
TI  - rSNPBase: a database for curated regulatory SNPs.
AB  - In recent years, human regulatory SNPs (rSNPs) have been widely studied. Here, we
      present database rSNPBase, freely available at http://rsnp.psych.ac.cn/, to
      provide curated rSNPs that analyses the regulatory features of all SNPs in the
      human genome with reference to experimentally supported regulatory elements. In
      contrast with previous SNP functional annotation databases, rSNPBase is
      characterized by several unique features. (i) To improve reliability, all SNPs in
      rSNPBase are annotated with reference to experimentally supported regulatory
      elements. (ii) rSNPBase focuses on rSNPs involved in a wide range of regulation
      types, including proximal and distal transcriptional regulation and post
      transcriptional regulation, and identifies their potentially regulated genes.
      (iii) Linkage disequilibrium (LD) correlations between SNPs were analysed so that
      the regulatory feature is annotated to SNP-set rather than a single SNP. (iv)
      rSNPBase provides the spatio-temporal labels and experimental eQTL labels for
      SNPs. In summary, rSNPBase provides more reliable, comprehensive and user
      friendly regulatory annotations on rSNPs and will assist researchers in selecting
      candidate SNPs for further genetic studies and in exploring causal SNPs for in
      depth molecular mechanisms of complex phenotypes. 

PMID- 24285298
TI  - Bacillus subtilis RecA and its accessory factors, RecF, RecO, RecR and RecX, are
      required for spore resistance to DNA double-strand break.
AB  - Bacillus subtilis RecA is important for spore resistance to DNA damage, even
      though spores contain a single non-replicating genome. We report that
      inactivation of RecA or its accessory factors, RecF, RecO, RecR and RecX,
      drastically reduce survival of mature dormant spores to ultrahigh vacuum
      desiccation and ionizing radiation that induce single strand (ss) DNA nicks and
      double-strand breaks (DSBs). The presence of non-cleavable LexA renders spores
      less sensitive to DSBs, and spores impaired in DSB recognition or end-processing
      show sensitivities to X-rays similar to wild-type. In vitro RecA cannot compete
      with SsbA for nucleation onto ssDNA in the presence of ATP. RecO is sufficient,
      at least in vitro, to overcome SsbA inhibition and stimulate RecA polymerization
      on SsbA-coated ssDNA. In the presence of SsbA, RecA slightly affects DNA
      replication in vitro, but addition of RecO facilitates RecA-mediated inhibition
      of DNA synthesis. We propose that repairing of the DNA lesions generates a
      replication stress to germinating spores, and the RecA.ssDNA filament might act
      by preventing potentially dangerous forms of DNA repair occurring during
      replication. RecA might stabilize a stalled fork or prevent or promote
      dissolution of reversed forks rather than its cleavage that should require end
      processing. 

PMID- 24285299
TI  - YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment.
AB  - Polycomb Group (PcG) proteins are crucial for epigenetic inheritance of cell
      identity and are functionally conserved from Drosophila to humans. PcG proteins
      regulate expression of homeotic genes and are essential for axial body patterning
      during development. Earlier we showed that transcription factor YY1 functions as
      a PcG protein. YY1 also physically interacts with YAF2, a homolog of RYBP. Here
      we characterize the mechanism and physiologic relevance of this interaction. We
      found phenotypic and biochemical correction of dRYBP mutant flies by mouse YAF2
      demonstrating functional conservation across species. Further biochemical
      analysis revealed that YAF2 bridges interaction between YY1 and the PRC1 complex.
      ChIP assays in HeLa cells showed that YAF2 is responsible for PcG recruitment to
      DNA, which is mediated by YY1 DNA binding. Knock-down of YY1 abrogated PcG
      recruitment, which was not compensated by exogenous YAF2 demonstrating that YY1
      DNA binding is a priori necessary for Polycomb assembly on chromatin. Finally, we
      found that although YAF2 and RYBP regulate a similar number of Polycomb target
      genes, there are very few genes that are regulated by both implying functional
      distinction between the two proteins. We present a model of YAF2-dependent and
      independent PcG DNA recruitment by YY1. 

PMID- 24285300
TI  - The Mouse Genome Database: integration of and access to knowledge about the
      laboratory mouse.
AB  - The Mouse Genome Database (MGD) (http://www.informatics.jax.org) is the community
      model organism database resource for the laboratory mouse, a premier animal model
      for the study of genetic and genomic systems relevant to human biology and
      disease. MGD maintains a comprehensive catalog of genes, functional RNAs and
      other genome features as well as heritable phenotypes and quantitative trait
      loci. The genome feature catalog is generated by the integration of computational
      and manual genome annotations generated by NCBI, Ensembl and Vega/HAVANA. MGD
      curates and maintains the comprehensive listing of functional annotations for
      mouse genes using the Gene Ontology, and MGD curates and integrates comprehensive
      phenotype annotations including associations of mouse models with human diseases.
      Recent improvements include integration of the latest mouse genome build
      (GRCm38), improved access to comparative and functional annotations for mouse
      genes with expanded representation of comparative vertebrate genomes and new
      loads of phenotype data from high-throughput phenotyping projects. All MGD
      resources are freely available to the research community. 

PMID- 24285301
TI  - AVPdb: a database of experimentally validated antiviral peptides targeting
      medically important viruses.
AB  - Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by
      targeting various stages of their life cycle. Therefore, we have developed AVPdb,
      available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated
      resource of experimentally verified AVPs targeting over 60 medically important
      viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we
      have separately provided HIV inhibiting peptides in 'HIPdb'. AVPdb contains
      detailed information of 2683 peptides, including 624 modified peptides
      experimentally tested for antiviral activity. In modified peptides a chemical
      moiety is attached for increasing their efficacy and stability. Detailed
      information include: peptide sequence, length, source, virus targeted, virus
      family, cell line used, efficacy (qualitative/quantitative), target step/protein,
      assay used in determining the efficacy and PubMed reference. The database also
      furnishes physicochemical properties and predicted structure for each peptide. We
      have provided user-friendly browsing and search facility along with other
      analysis tools to help the users. Entering of many synthetic peptide-based drugs
      in various stages of clinical trials reiterate the importance for the AVP
      resources. AVPdb is anticipated to cater to the needs of scientific community
      working for the development of antiviral therapeutics. 

PMID- 24285302
TI  - Locus Reference Genomic: reference sequences for the reporting of clinically
      relevant sequence variants.
AB  - Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain
      internationally recognized stable reference sequences designed specifically for
      reporting clinically relevant sequence variants. Each LRG is contained within a
      single file consisting of a stable 'fixed' section and a regularly updated
      'updatable' section. The fixed section contains stable genomic DNA sequence for a
      genomic region, essential transcripts and proteins for variant reporting and an
      exon numbering system. The updatable section contains mapping information,
      annotation of all transcripts and overlapping genes in the region and legacy exon
      and amino acid numbering systems. LRGs provide a stable framework that is vital
      for reporting variants, according to Human Genome Variation Society (HGVS)
      conventions, in genomic DNA, transcript or protein coordinates. To enable
      translation of information between LRG and genomic coordinates, LRGs include
      mapping to the human genome assembly. LRGs are compiled and maintained by the
      National Center for Biotechnology Information (NCBI) and European Bioinformatics
      Institute (EBI). LRG reference sequences are selected in collaboration with the
      diagnostic and research communities, locus-specific database curators and
      mutation consortia. Currently >700 LRGs have been created, of which >400 are
      publicly available. The aim is to create an LRG for every locus with clinical
      implications. 

PMID- 24285303
TI  - Syn5 RNA polymerase synthesizes precise run-off RNA products.
AB  - The enzyme predominantly used for in vitro run-off RNA synthesis is bacteriophage
      T7 RNA polymerase. T7 RNA polymerase synthesizes, in addition to run-off products
      of precise length, transcripts with an additional non-base-paired nucleotide at
      the 3'-terminus (N+1 product). This contaminating product is extremely difficult
      to remove. We recently characterized the single-subunit RNA polymerase from
      marine cyanophage Syn5 and identified its promoter sequence. This marine enzyme
      catalyses RNA synthesis over a wider range of temperature and salinity than does
      T7 RNA polymerase. Its processivity is >30,000 nt without significant
      intermediate products. The requirement for the initiating nucleotide at the
      promoter is less stringent for Syn5 RNA polymerase as compared to T7 RNA
      polymerase. A major difference is the precise run-off transcripts with
      homogeneous 3'-termini synthesized by Syn5 RNA polymerase. Therefore, the enzyme
      is advantageous for the production of RNAs that require precise 3'-termini, such
      as tRNAs and RNA fragments that are used for subsequent assembly.

PMID- 24285304
TI  - megaTALs: a rare-cleaving nuclease architecture for therapeutic genome
      engineering.
AB  - Rare-cleaving endonucleases have emerged as important tools for making targeted
      genome modifications. While multiple platforms are now available to generate
      reagents for research applications, each existing platform has significant
      limitations in one or more of three key properties necessary for therapeutic
      application: efficiency of cleavage at the desired target site, specificity of
      cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile
      means for delivery to desired target cells. Here, we describe the development of
      a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL',
      in which the DNA binding region of a transcription activator-like (TAL) effector
      is used to 'address' a site-specific meganuclease adjacent to a single desired
      genomic target site. This architecture allows the generation of extremely active
      and hyper-specific compact nucleases that are compatible with all current viral
      and nonviral cell delivery methods. 

PMID- 24285305
TI  - NONCODEv4: exploring the world of long non-coding RNA genes.
AB  - NONCODE (http://www.bioinfo.org/noncode/) is an integrated knowledge database
      dedicated to non-coding RNAs (excluding tRNAs and rRNAs). Non-coding RNAs
      (ncRNAs) have been implied in diseases and identified to play important roles in
      various biological processes. Since NONCODE version 3.0 was released 2 years ago,
      discovery of novel ncRNAs has been promoted by high-throughput RNA sequencing
      (RNA-Seq). In this update of NONCODE, we expand the ncRNA data set by collection
      of newly identified ncRNAs from literature published in the last 2 years and
      integration of the latest version of RefSeq and Ensembl. Particularly, the number
      of long non-coding RNA (lncRNA) has increased sharply from 73 327 to 210 831.
      Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA
      genes was put forward to help systematic understanding of lncRNAs. The 56 018 and
      46 475 lncRNA genes were generated from 95 135 and 67 628 lncRNAs for human and
      mouse, respectively. Additionally, we present expression profile of lncRNA genes
      by graphs based on public RNA-seq data for human and mouse, as well as predict
      functions of these lncRNA genes. The improvements brought to the database also
      include an incorporation of an ID conversion tool from RefSeq or Ensembl ID to
      NONCODE ID and a service of lncRNA identification. NONCODE is also accessible
      through http://www.noncode.org/. 

PMID- 24285307
TI  - The influence of van der Waals forces on droplet morphological transitions and
      solvation forces in nanochannels.
AB  - The morphological phase transition between sessile and lenticular shapes of a
      droplet placed in a nanochannel is observed upon increasing the droplet volume.
      The phase diagram for this system is discussed within both macroscopic and
      mesoscopic approaches. On the mesoscopic level, the van der Waals forces are
      taken into account via the effective interface potential acting between the
      channel walls and the droplet. We discuss the contact angle dependence on the
      droplet volume and the distance between the walls; this angle turns out to be
      smaller than the macroscopic Young's angle. The droplet's presence induces the
      solvation force acting between the channel walls. It can be either attractive or
      repulsive, depending on the width of the channel. 

PMID- 24285306
TI  - PortEco: a resource for exploring bacterial biology through high-throughput data
      and analysis tools.
AB  - PortEco (http://porteco.org) aims to collect, curate and provide data and
      analysis tools to support basic biological research in Escherichia coli (and
      eventually other bacterial systems). PortEco is implemented as a 'virtual' model
      organism database that provides a single unified interface to the user, while
      integrating information from a variety of sources. The main focus of PortEco is
      to enable broad use of the growing number of high-throughput experiments
      available for E. coli, and to leverage community annotation through the EcoliWiki
      and GONUTS systems. Currently, PortEco includes curated data from hundreds of
      genome-wide RNA expression studies, from high-throughput phenotyping of single
      gene knockouts under hundreds of annotated conditions, from chromatin
      immunoprecipitation experiments for tens of different DNA-binding factors and
      from ribosome profiling experiments that yield insights into protein expression.
      Conditions have been annotated with a consistent vocabulary, and data have been
      consistently normalized to enable users to find, compare and interpret relevant
      experiments. PortEco includes tools for data analysis, including clustering,
      enrichment analysis and exploration via genome browsers. PortEco search and data
      analysis tools are extensively linked to the curated gene, metabolic pathway and
      regulation content at its sister site, EcoCyc. 

PMID- 24285308
TI  - Exceptionally fast water desalination at complete salt rejection by pristine
      graphyne monolayers.
AB  - Desalination that produces clean freshwater from seawater holds the promise of
      solving the global water shortage for drinking, agriculture and industry.
      However, conventional desalination technologies such as reverse osmosis and
      thermal distillation involve large amounts of energy consumption, and the
      semipermeable membranes widely used in reverse osmosis face the challenge to
      provide a high throughput at high salt rejection. Here we find by comprehensive
      molecular dynamics simulations and first principles modeling that pristine
      graphyne, one of the graphene-like one-atom-thick carbon allotropes, can achieve
      100% rejection of nearly all ions in seawater including Na(+), Cl(-), Mg(2+),
      K(+) and Ca(2+), at an exceptionally high water permeability about two orders of
      magnitude higher than those for commercial state-of-the-art reverse osmosis
      membranes at a salt rejection of ~98.5%. This complete ion rejection by graphyne,
      independent of the salt concentration and the operating pressure, is revealed to
      be originated from the significantly higher energy barriers for ions than for
      water. This intrinsic specialty of graphyne should provide a new possibility for
      the efforts to alleviate the global shortage of freshwater and other
      environmental problems.

PMID- 24285309
TI  - An unusual triphenylphosphine oxide catalyzed stereoselective 1,3-dichlorination
      of unsaturated ketoesters.
AB  - An unusual Ph3PO-catalyzed stereoselective 1,3-dicholorination of an unsaturated
      ketoester has been developed. The novel activation mode involved in this cascade
      reaction can promote consecutively elusive transformations. The products were
      obtained with good yields and excellent stereoselectivities. This reaction makes
      important complementation to the limitations associated with the field of
      dichlorination.

PMID- 24285310
TI  - [Sport injuries in full contact and semi-contact karate].
AB  - BACKGROUND: Karate enjoys great popularity both in professional and recreational
      sports and can be classified into full, half and low contact styles. The aim of
      this study was the analysis of sports injuries in Kyokushinkai (full contact) and
      traditional Karate (semi-contact). METHODS: In a retrospective study design, 215
      active amateur karateka (114 full contact, 101 semi-contact) were interviewed by
      means of a standardised questionnaire regarding typical sport injuries during the
      last 36 months. Injuries were categorised into severity grade I (not requiring
      medical treatment), grade II (single medical treatment), grade III (several
      outpatient medical treatments) and grade IV (requiring hospitalisation). RESULTS:
      In total, 217 injuries were reported in detail. 125 injuries (58%) occurred in
      full contact and 92 (42%) in semi-contact karate. The time related injury rate of
      full contact karateka was 1.9/1000 h compared to 1.3/1000 h of semi-contact
      karateka (p < 0.05). The most common types of injuries were musculoskeletal
      contusions (33% full contact, 20% semi-contact), followed by articular sprains
      with 19% and 16%. The lower extremity was affected twice as often in full contact
      (40%) as in semi-contact (20%) karate. Training injuries were reported by 80% of
      the full contact and 77% of the semi-contact karateka. Most injuries, both in
      training and competition, occurred in kumite. 75% of the reported injuries of
      full contact and 70% of semi-contact karateka were classified as low grade (I or
      II). CONCLUSION: The high rate of injuries during training and kumite (sparring)
      points to specific prevention goals. The emphasis should be put on proprioceptive
      training and consistent warm-up. In the actual competition the referees play a
      vital role regarding prevention.

PMID- 24285311
TI  - Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the
      brain with positron emission tomography.
AB  - Exploration of the living human brain in real-time and in a noninvasive way was
      for centuries only a dream, made, however, possible today with the remarkable
      development during the four last decades of powerful molecular imaging
      techniques, and especially positron emission tomography (PET). Molecular PET
      imaging relies, from a chemical point of view, on the use and preparation of a
      positron-emitting radiolabelled probe or radiotracer, notably compounds
      incorporating one of two short-lived radionuclides fluorine-18 (T1/2 : 109.8 min)
      and carbon-11 (T1/2 : 20.38 min). The growing availability and interest for the
      radiohalogen fluorine-18 in radiopharmaceutical chemistry undoubtedly results
      from its convenient half-life and the successful use in clinical oncology of 2
      [(18) F]fluoro-2-deoxy-d-glucose ([(18) F]FDG). The special interest of carbon-11
      is not only that carbon is present in virtually all biomolecules and drugs
      allowing therefore for isotopic labelling of their chemical structures but also
      that a given molecule could be radiolabelled at different functions or sites,
      permitting to explore (or to take advantage of) in vivo metabolic pathways. PET
      chemistry includes production of these short-lived radioactive isotopes via
      nuclear transmutation reactions using a cyclotron, and is directed towards the
      development of rapid synthetic methods, at the trace level, for the introduction
      of these nuclides into a molecule, as well as the use of fast purification,
      analysis and formulation techniques. PET chemistry is the driving force in
      molecular PET imaging, and this special issue of the Journal of Labelled
      Compounds and Radiopharmaceuticals, which is strongly chemistry and
      radiochemistry-oriented, aims at illustrating, be it in part only, the state-of
      the-art arsenal of reactions currently available and its potential for the
      research and development of specific molecular probes labelled with the positron
      emitters carbon-11 and fluorine-18, with optimal imaging properties for PET
      exploration of the brain.

PMID- 24285312
TI  - Radioligands targeting P-glycoprotein and other drug efflux proteins at the blood
      brain barrier.
AB  - Brain penetration of radiopharmaceuticals or therapeutic drugs may be restricted
      by adenosine triphosphate-binding cassette (ABC) transporters, such as P
      glycoprotein (Pgp), breast cancer resistance protein (BCRP), or the multidrug
      resistance-associated proteins. These transporters are expressed in the luminal
      membrane of brain capillary endothelial cells forming the blood-brain barrier
      (BBB), where they actively efflux a wide range of chemically unrelated compounds
      from the brain back into the blood. Most efforts to visualize ABC transporters at
      the BBB with positron emission tomography have concentrated on Pgp. Pgp imaging
      probes can be classified as radiolabeled substrates or inhibitors. The
      radiolabeled substrates (R)-[(11) C]verapamil and [(11) C]-N-desmethyl-loperamide
      have been successfully used to assess Pgp function at the BBB of animals and
      humans. Radiolabeled Pgp inhibitors, such as [(11) C]tariquidar, [(11)
      C]elacridar, or [(11) C]laniquidar, were developed to measure Pgp expression
      levels at the BBB, which has so far remained unsuccessful as these probes were
      unexpectedly recognized at tracer concentrations by Pgp and BCRP as substrates
      resulting in low brain uptake. Studies on positron emission tomography tracers
      for other ABC transporters than Pgp (BCRP and multidrug resistance-associated
      proteins) are still in their infancy. It is hoped that the experience gained with
      the imaging of Pgp will be successfully translated to the development of
      radiotracers to visualize other ABC transporters.

PMID- 24285313
TI  - Radiochemistry devoted to the production of monoamine oxidase (MAO-A and MAO-B)
      ligands for brain imaging with positron emission tomography.
AB  - Monoamine oxidase (MAO) belongs to a family of flavin-containing integral enzymes
      that are present in the outer mitochondrial membrane in neurons and glial cells
      in the central nervous system. These enzymes catalyze the oxidative deamination
      of various neurotransmitters, biogenic amines, and xenobiotics, thereby
      influencing their availability and physiological activity in brain and body. Over
      the past decades, many potential positron emission tomography tracers have been
      put forward to visualize MAO in the brain with varying success, and recent
      publications on the topic illustrate the continuing interest in the field. The
      present review gives an overview of the compounds that have been put forward as
      possible MAO tracers in the brain and focuses on the radiochemical procedures
      that have been developed to produce them up till now. Relevant radioligands are
      grouped by the main radiochemical strategies that have been employed to
      synthesize them, and some interesting details and findings that are crucial to
      the radiosyntheses are provided. 

PMID- 24285315
TI  - The potential of carbon-11 and fluorine-18 chemistry: illustration through the
      development of positron emission tomography radioligands targeting the
      translocator protein 18 kDa.
AB  - The TSPO (translocator protein), also known as the peripheral benzodiazepine
      receptor, is upregulated in the brain of subjects suffering from
      neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's
      disease. Moreover, this overexpression has been proved to be linked to microglia
      activation making thus the TSPO a marker of choice of neuroinflammatory processes
      and therefore a potential target for the development of radioligands for positron
      emission tomography imaging. The discovery of selective TSPO ligands and their
      labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine
      18 emerged in the mid-1980s with the preparation of the 3-isoquinolinecarboxamide
      [(11) C]PK11195. To date, an impressive number of promising compounds-[(11)
      C]PK11195-challengers-have been developed; some radioligands-for example, [(11)
      C]PBR28, [(11) C]DPA-713, [(18) F]FEDAA1106 and [(18) F]DPA-714-are currently
      used in clinical trials. As illustrated in this review, the methodologies applied
      for the preparation of these compounds remain mainly [(11) C]methylations using
      [(11) C]MeI or [(11) C]MeOTf and SN 2-type nucleophilic aliphatic [(18)
      F]fluorinations-two processes illustrating the state-of-the-art arsenal of
      reactions that involves these two short-lived radioisotopes-but alternative
      processes, such as [(11) C]carbonylations using [(11) C]CO and [(11) C]COCl2 as
      well as SN Ar-type nucleophilic [(18) F]fluorinations, have also been reported
      and as such, reviewed herein. 

PMID- 24285314
TI  - Positron emission tomography radioligands for in vivo imaging of Abeta plaques.
AB  - The development of positron emission tomography (PET) radioligands for the non
      invasive imaging of amyloid-beta plaque burden has been the focus of intense
      research efforts over the last decade. A variety of structural backbones have
      been investigated and several radiolabeled molecules have been evaluated in phase
      I (and later) clinical studies. These efforts have been driven by the desire not
      only to develop a suitable diagnostic imaging agent but also to develop a means
      to evaluate potential therapies for Alzheimer's disease. This review focuses on
      the development of these ligands, as well as the radiochemistry and current
      regulatory status of these PET radioligands. Particular attention is given to
      those ligands that have progressed to the later stages of drug development (phase
      II/III clinical trial studies) or approved New Drug Application status. 

PMID- 24285316
TI  - Current status of positron emission tomography radiotracers for serotonin
      receptors in humans.
AB  - Serotonin (5-HT) neurotransmission plays a key modulatory role in the brain. This
      system is critical for pathophysiological processes and many drug treatments for
      brain disorders interact with its 14 subtypes of receptors. Positron emission
      tomography (PET) is a unique tool for the study of the living brain in
      translational studies from animal models to patients in neurology or psychiatry.
      This short review is intended to cover the current status of PET radioligands
      used for imaging human brain 5-HT receptors. Here, we describe the available PET
      radioligands for the 5-HT1A , 5-HT1B , 5-HT2A , 5-HT4 and 5-HT6 receptors.
      Finally, we highlight the future challenges for a functional PET imaging of
      serotonin receptors, including the research towards specific PET radiotracers for
      yet unexplored serotonin receptors, the need of radiotracers for endogenous
      serotonin level measurement and the contribution of agonist radiotracers for
      functional imaging of 5-HT neurotransmission. 

PMID- 24285317
TI  - (11) C and (18) F PET radioligands for the serotonin transporter (SERT).
AB  - The serotonin transporter (SERT) has been implicated in a variety of
      neuropsychiatric disorders including depression, anxiety, and suicide, and is the
      target of the selective serotonin reuptake inhibitor (SSRI) class of
      antidepressants. The availability of SERT-specific positron emission tomography
      (PET) radioligands will allow the SERT to be studied noninvasively in living
      subjects through PET imaging of the SERT and occupancy studies of SSRIs. Numerous
      diaryl sulfide and tropane derivatives have been developed and radiolabeled with
      (11) C or (18) F for imaging the SERT with PET. 

PMID- 24285318
TI  - (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of
      histamine receptors in the brain.
AB  - The signaling molecule histamine plays a key role in the mediation of immune
      reactions, in gastric secretion, and in the sensory system. In addition, it has
      an important function as a neurotransmitter in the central nervous system, acting
      in pituitary hormone secretion, wakefulness, motor and cognitive functions, as
      well as in itch and nociception. This has raised interest in the role of the
      histaminergic system for the treatment and diagnosis of various pathologies such
      as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation,
      mood disorders, and pruritus. In the past 20 years, several ligands targeting the
      four different histamine receptor subtypes have been explored as potential
      radiotracers for positron emission tomography (PET). This contribution provides
      an overview of the developments of subtype-selective carbon-11-labeled and
      fluorine-18-labeled compounds for imaging in the brain. Using specific
      radioligands, the H1 R expression in human brain could be examined in diseases
      such as schizophrenia, depression, and anorexia nervosa. In addition, the
      sedative effects of antihistamines could be investigated in terms of H1 R
      occupancy. The H3 R is of special interest because of its regulatory role in the
      release of various other neurotransmitters, and initial H3 R PET imaging studies
      in humans have been reported. The H4 R is the youngest member of the histamine
      receptor family and is involved in neuroinflammation and various sensory
      pathways. To date, two H4 R-specific (11) C-labeled ligands have been
      synthesized, and the imaging of the H4 R in vivo is in the early stage. 

PMID- 24285319
TI  - Radioligands for the dopamine receptor subtypes.
AB  - The actions of the predominant neurotransmitter in the brain, dopamine, are
      mediated by the postsynaptic dopamine receptors. The five dopamine receptor
      subtypes and their regulation have been associated with a large variety of
      psychiatric diseases. Therefore, positron emission tomography (PET) imaging
      studies using suitable and selective (18) F-labeled and (11) C-labeled dopamine
      receptor radioligands could provide valuable knowledge on the impact of receptor
      density on the pathogenesis and evolvement of neuropsychiatric and neurological
      diseases. This special issue subchapter provides a summary of the most important
      (18) F-labeled and (11) C-labeled radioligands for PET imaging of the dopamine
      receptor subtypes, their radiochemistry, and characteristics from in vitro and in
      vivo applications, considering not only the already established PET ligands but
      also the recently published preclinical work.

PMID- 24285320
TI  - Tropane-derived (11) C-labelled and (18) F-labelled DAT ligands.
AB  - Radiolabelling of cocaine-derived 3-phenyltropanes for dopamine transporter
      positron emission tomography with (18) F and (11) C is reviewed.

PMID- 24285321
TI  - Recent PET radioligands with optimal brain kinetics for imaging nicotinic
      acetylcholine receptors.
AB  - Cerebral neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in
      various neurophysiological processes and in the pathophysiology and/or treatment
      strategies of various disorders. Positron emission tomography (PET) imaging of
      nAChR and, especially, the most prominent cerebral subtype alpha4beta2-nAChR is
      important in smoking, epilepsy, attention deficit hyperactivity disorder,
      depression, schizophrenia, cognition, behavior, memory, and in research involving
      aging, cognitive impairments, and dementia. Most human alpha4beta2-nAChR PET
      imaging has been performed with 2-[(18) F]FA, but slow brain kinetics is the
      substantial drawback of 2-[(18) F]FA that precludes widespread PET imaging
      research of nAChR in humans. Development of a better PET radioligand for
      alpha4beta2-nAChR was a focus of substantial investigation that has been
      thoroughly reviewed (up to 2009) previously. This article attempts to summarize
      the peer-reviewed publications of the most recent development and preclinical
      studies of novel alpha4beta2-nAChR PET radioligands with improved brain kinetics
      and first human studies with one of these radioligands ([(18) F]AZAN). 

PMID- 24285322
TI  - PET radioligands for the vesicular transporters for monoamines and acetylcholine.
AB  - The vesicular transporters for the monoamine and acetylcholine have been
      successfully targeted for the development of radioligands for human brain
      imaging. The vesicular monoamine transporter type 2 ligands are based on the
      structure of tetrabenazine, a known clinically used drug. In contrast, the
      radioligands for vesicular acetylcholine transporter are based on vesamicol, a
      toxic xenobiotic. The similarities and differences in the development of these
      two classes of radioligands are discussed.

PMID- 24285323
TI  - PET probes for imaging brain acetylcholinesterase.
AB  - Imaging acetylcholinesterase (AChE) is valuable not only for diagnosing and
      understanding dementia but also for monitoring the effects of cholinesterase
      inhibitors used as antidementia drugs and for determining the appropriate
      clinical dosage of newly developed cholinesterase inhibitors. The distribution of
      AChE in the living brain can be imaged with two different types of radioprobes,
      including substrate-type and ligand-type probes. The substrate-type positron
      emission tomography (PET) probes, N-[(11) C]methylpiperidin-4-yl acetate ([(11)
      C]MP4A), and its propionate, [(11) C]MP4P, have been widely used in clinical
      studies of dementia, including Alzheimer's disease. [(11) C]MP4A and [(11) C]MP4P
      have been used to demonstrate a reduction in AChE activity in the brains of
      dementia patients, as well as the bioavailability of AChE inhibitors, leading to
      the subsequent development of the widely available (18) F-labeled derivatives of
      MP4A. In addition, several radiolabeled cholinesterase inhibitors have been
      developed as PET probes for AChE mapping in the brain. Herein, we have reviewed
      the development of PET probes for the imaging of AChE in the brain and described
      the principles of measuring AChE activity in the brain using PET with substrate
      type radioprobes. A discussion of the reagents developed from substrate-type PET
      probes for the specific measurement of AChE activity in vitro has also been
      provided. 

PMID- 24285324
TI  - Radiosynthesis of carbon-11 and fluorine-18 labelled radiotracers to image the
      ionotropic and metabotropic glutamate receptors.
AB  - l-Glutamate is the major neurotransmitter in the central nervous system and
      activates both ionotropic and metabotropic receptors. Here the radiosynthesis of
      radiotracers developed for both types of receptors are reviewed with a highlight
      on the radiopharmaceuticals used or evaluated in humans. At first, radiotracers
      were developed for ionotropic N-methyl-d-aspartate receptors without any success
      to obtain radiopharmaceuticals useable for clinical or even preclinical positron
      emission tomography (PET) imaging purposes. Some compounds were radiolabelled and
      evaluated for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
      without any successful results. The recent development of radiotracers for
      metabotropic glutamate receptors was more efficient because radiopharmaceuticals
      are currently evaluated or used in clinical trials to study the mGluR1, mGluR2 or
      mGluR5 receptors by PET. Although the majority of the radiotracers were
      classically labelled with carbon-11 by O- or N-[(11) C]-methylation or with
      fluorine-18 nucleophilic substitution of aromatic nitro or halogeno precursors
      using krypofix 2.2.2/potassium [(18) F]fluoride complex, some radiosyntheses were
      performed with recent radiolabelling reactions like the use of iodionium salt for
      [(18) F]-labelling.

PMID- 24285325
TI  - Positron emission tomography radioligands for the opioid system.
AB  - Opiate receptors are found in the brain, the spinal cord, some peripheral sensory
      neurons, and the gastrointestinal tract. Naturally occurring and synthetic opiate
      ligands exert their influence on a wide variety of processes including analgesia,
      euphoria, dysphoria, sedation, respiratory depression, and miosis and are
      frequently topics for discussions on addiction and physical dependence. This
      review looks at the history of positron emission tomography radioligands for
      probing this receptor system. 

PMID- 24285326
TI  - PET radioligands targeting the brain GABAA /benzodiazepine receptor complex.
AB  - The development of positron emission tomography radioligands for the GABAA
      /benzodiazepine receptor complex (GABAA receptor) labeled with (11) C and (18) F
      is examined. The review covers labeling strategies as well as brief biological
      evaluations of radioligands. In addition, we assess the special considerations
      that must be taken during a development program for radioligands targeting the
      GABAA receptor and explore some of the challenges that lie ahead.

PMID- 24285327
TI  - Synthetic strategies for radioligands for in vivo imaging of brain cannabinoid
      type-1 receptors.
AB  - Despite its abundant expression in the brain, the cannabinoid type-1 (CB1)
      receptor was discovered only in 1988. During the last decade, efforts from
      several research groups have made it possible to visualize the CB1 receptor in
      vivo to unravel its role in the brain physiology and pathology. This review
      discusses strategies for (radio)synthesis of radioligands for in vivo imaging of
      CB1 receptors. 

PMID- 24285328
TI  - The development of radiotracers for imaging sigma (sigma) receptors in the
      central nervous system (CNS) using positron emission tomography (PET).
AB  - Sigma (sigma) receptors are unique mammalian proteins, distributed in the central
      nervous system and elsewhere, which are increasingly implicated in the
      pathophysiology of virtually all major central nervous system disorders. The
      heterogeneous but wide distribution of sigma1 in the brain has prompted the
      development of selective radiotracers for imaging these sites using positron
      emission tomography (PET). To date, some 50 carbon-11-labelled and fluorine-18
      labelled candidate PET radioligands targeting sigma receptors have been reported.
      The historical development of selective sigma1 receptor ligands as potential PET
      imaging agents, as well as the radiochemistry and application of the most
      recently developed examples, is described herein. 

PMID- 24285329
TI  - Methods for (11) C- and (18) F-labelling of amino acids and derivatives for
      positron emission tomography imaging.
AB  - The different concepts realized for the synthesis of (11) C- and (18) F-labelled
      amino acids are summarized. Carbon-11 enables principally authentic
      radiolabelling of natural occurring amino acids by substituting one of the
      skeleton carbons by the radionuclide. Fluorine-18 is a foreign element for
      natural amino acids. Because of its advantageous nuclidic properties for positron
      emission tomography, however, it becomes increasingly important in molecular
      imaging, also with amino acid analogues. Especially in the last decade,
      considerable progress has been made with the radiosynthesis of (18) F-labelled
      amino acids that are now clinically approved, and thus assure their availability.
      In contrast, the synthetic possibilities with (11) C-labelled amino acids are
      more limited because of the short half-life of carbon-11 which also hampers their
      wide spread use.

PMID- 24285330
TI  - Nucleoside-based probes for imaging tumor proliferation using positron emission
      tomography.
AB  - Cancer is one of the leading causes of human death, and early detection can be
      beneficial for its timely therapy and management. For the early detection of
      cancer, positron emission tomography (PET) is more accurate and sensitive than
      other imaging modalities, such as computed tomography and magnetic resonance
      imaging. [(18) F]-Labeled fluorodeoxyglucose is the most useful PET probe in
      early detection of cancer; however, its nonspecific accumulation and consequent
      false-positive findings warrant the identification of other PET probes. Thymidine
      (TdR) and its analogs have been radiolabeled for PET imaging of cellular
      proliferation and DNA synthesis. Because of its in vivo instability, radiolabeled
      TdR has not been successful in PET imaging. However, some of its radiolabeled
      analogs have been developed for PET imaging of cellular proliferation and DNA
      synthesis. In this review, the radiochemistry and production of (11) C-TdR and
      (11) C/(18) F-labeled TdR analogs published to date are presented.

PMID- 24285331
TI  - Positron emission tomography radiotracers for imaging hypoxia.
AB  - Localized hypoxia, the physiological hallmark of many clinical pathologies, is
      the consequence of acute or chronic ischemia in the affected region or tissue.
      The versatility, sensitivity, quantitative nature, and increasing availability of
      positron emission tomography (PET) make it the preclinical and clinical method of
      choice for functional imaging of tissue hypoxia at the molecular level. The
      progress and current status of radiotracers for hypoxia-specific PET imaging are
      reviewed in this article including references mainly focused on radiochemistry
      and also relevant to molecular imaging of hypoxia in preclinical and clinical
      studies. 

PMID- 24285332
TI  - Endogenous compounds labeled with radionuclides of short half-life-some
      perspectives.
AB  - In the article, the strategy and synthesis of some endogenous compounds labeled
      mainly with (11) C are presented. There are some examples illustrating how
      endogenous labeled compounds in connection with positron emission tomography have
      unique properties to describe various biological processes, and a few examples of
      the use of tracers labeled with (13) N and (15) O are also discussed. Labeled
      endogenous compounds may be an important asset to describe the conditions and the
      status of biological systems and might therefore be a key for the future search
      of individualized medicine.

PMID- 24285334
TI  - Redox proteomics: from protein modifications to cellular dysfunction and disease.

PMID- 24285335
TI  - Changing the way we work: elevating energy expenditure with workstation
      alternatives.
AB  - Emerging evidence supports the feasibility of raising daily energy expenditure
      (EE) by replacing office work-related sedentary behavior with low-intensity non
      exercise physical activity (PA) via workstation alternatives to the traditional
      office chair and desktop computer-based combinations. The purpose of this review
      article is to introduce a simple taxonomy to facilitate classification and study
      of workstation alternatives, catalog the diversity of research undertaken to date
      related to energy balance, and present and summarize the gaps and opportunities
      for a research agenda for workstation alternatives moving forward. A PubMed
      search elicited 57 English language articles published since 2000; additional
      articles were identified by reviewing reference sections and contacting authors.
      Selection criteria ultimately focused on use of workstation alternatives during
      simulated or real work tasks. The EE of sitting on a stability ball or using sit
      stand/standing desks is comparable to the traditional seated condition (?1.2 kcal
      min(-1)). The treadmill and pedal desks (active workstation alternatives) offer
      the greatest promise in terms of EE (?2-4 kcal min(-1)). Sitting on a stability
      ball or using sit-stand/standing desks does not impair task performance relative
      to the traditional seated condition. Some evidence of typing impairment is
      inconsistently reported with active workstation alternatives; the finer motor
      skills required for mouse-related tasks may be more affected. Little is known
      about learning or adaptation with practice. Users are generally accepting of
      workstation alternatives; however, there is evidence of less than optimal use.
      Active workstations (that is, treadmill desks and pedal desks) in particular
      represent a potential strategy for mitigating the diminished EE inherent to
      contemporary office-based workplaces, but only if they are scalable. The science
      supporting active workstations is young and heterogeneous; however, this means
      that there are many knowledge gaps and opportunities for research, including
      those focused on implementation issues related to optimizing both employers' and
      workers' uptake. 

PMID- 24285337
TI  - Clinical outcomes associated with the early postoperative use of heparin in
      pancreas transplantation.
AB  - BACKGROUND: Graft thrombosis following pancreas transplantation is the leading
      non-immunologic cause of graft loss. Routine systemic anticoagulation is
      controversial because of an increased bleeding risk. METHODS: This was a
      retrospective, single-center analysis including all pancreas transplants
      performed over 9 years evaluating the use of low-dose heparin in the early
      postoperative period. Clinical outcomes were partial and complete graft
      thrombosis within 30 days, bleeding events, relaparotomy rates, and 30-day graft
      and patient survival. Multivariate regression analysis was performed to identify
      risk factors for early graft loss resulting from thrombosis. RESULTS: One hundred
      fifty-two patients were included, 52 in the heparin group. The overall complete
      thrombosis rate was 13.1%, 10% in those who received heparin, and 15% in those
      who did not. Partial thrombosis was higher in the heparin group (10% vs. 3%).
      Higher relaparotomy rates were seen in the heparin group (29% vs. 22%); however,
      bleeding events were similar between groups. Graft and patient survival at 30
      days were similar between groups; however, there was a trend toward higher graft
      survival in the heparin group. Heparin showed a trend toward a protective benefit
      for early graft loss resulting from thrombosis in all multivariate regression
      models. CONCLUSION: These data suggest low-dose heparin early in the
      postoperative period may provide a protective benefit in the prevention of early
      graft loss resulting from thrombosis, without an increased risk of bleeding.

PMID- 24285336
TI  - Light physical activity determined by a motion sensor decreases insulin
      resistance, improves lipid homeostasis and reduces visceral fat in high-risk
      subjects: PreDiabEx study RCT.
AB  - OBJECTIVE: To examine physical activity (PA) thresholds affecting glucose,
      insulin and lipid concentrations and body fat composition in high-risk patients
      for type 2 diabetes (T2D). INTERVENTION: A total of 113 subjects of both genders
      having abnormal glucose levels in the oral glucose tolerance test were contacted.
      A total of 78 subjects with age 58.8+/-10.4 years and body mass index 31.7+/-5.3
      kg m(-2) were randomly assigned to intervention and control groups. INTERVENTION
      consisted of a supervised walking (60 min three times weekly) for 3 months. All
      the subjects received standard care for PA and weight reduction and wore an
      accelerometer during the whole wakeful time. RESULTS: Over 80% of the daily steps
      clustered at an acceleration level of 0.3-0.7 g (2-3 km h(-1) of walking) and
      were 5870 in the intervention and 4434 in the control group (P<0.029). Between 0
      and 3 months no significant changes were observed in fasting and 2-h glucose,
      body weight or maximal oxygen uptake. In contrast, changes in fasting and 2-h
      insulin (-3.4 mU l(-1), P=0.035 and -26.6, P=0.003, respectively), homeostasis
      model assessment-estimated insulin resistance (-1.0, P=0.036), total cholesterol
      (-0.55 mmol l(-1), P=0.041), low-density lipoprotein (LDL) cholesterol (-0.36
      mmol l(-1), P=0.008) and visceral fat area (-5.5 cm(2), P=0.030) were
      significantly greater in the intervention than in control subjects. The overall
      effects of PA were analyzed by quartiles of daily steps of all subjects. There
      were significant reductions in total and LDL cholesterol and visceral fat area
      between the highest (daily steps over 6520) and the lowest quartile (1780-2810
      daily steps). The changes associated with PA remained significant after
      adjustments of baseline, sex, age and body weight change. CONCLUSION: Habitual
      and structured PAs with the acceleration levels of 0.3-0.7 g and daily steps over
      6520, equivalent to walking at 2-3 km h(-1) for 90 min daily, standing for the
      relative PA intensity of 30-35% of the maximal oxygen uptake, are clinically
      beneficial for overweight/obese and physically inactive individuals with a high
      risk for T2D.

PMID- 24285338
TI  - HMG CoA reductase inhibitor treatment induces dysglycemia in renal allograft
      recipients.
AB  - BACKGROUND: Dysglycemia and dyslipidemia are important metabolic complications of
      organ transplantation. Statins are widely used to control dyslipidemia; however,
      long-term use of statins is related to diabetes mellitus (DM) and impaired
      fasting glucose (IFG). The aim of this study was to evaluate the influence of
      statins on the development of dysglycemia (IFG and/or DM) in renal allograft
      recipients. METHODS: A total of 394 patients without previously known DM or IFG
      who underwent kidney transplantation were enrolled. Patients were grouped into
      the two groups according to the use of statin (control, n=149; statin, n=245).
      The major statins used were fluvastatin (80 mg/d, n=134) and atorvastatin (20
      mg/d, n=111). We compared the incidence of IFG or DM during the follow-up period.
      RESULTS: The incidence of IFG was higher in the statin group than that in the
      control group (28.6% vs. 8.7%, P<0.001). The incidence of dysglycemia was
      significantly higher in the statin group (40.0% vs. 15.4%, P=0.001). Time to
      development of dysglycemia after transplantation was shorter in the statin group
      than in the control group (38.8+/-29.7 vs. 47.2+/-23.3 months, P=0.002). Statin
      use was associated with an increased risk for dysglycemia after adjustment for
      age, sex, body mass index, hypertension, cholesterol levels, hepatitis C
      infection, and type of immunosuppressant (hazard ratio=3.08, 95% confidence
      interval=1.91-4.98). The dysglycemic effect was more profound in the patients who
      used atorvastatin than in those who used fluvastatin (hazard ratio=2.21, 95%
      confidence interval=1.02-4.76). CONCLUSION: Statin treatment is associated with
      an elevation in fasting plasma glucose and in the development of dysglycemia in
      renal allograft recipients.

PMID- 24285339
TI  - Pre-implant biopsy predicts outcome of single-kidney transplantation independent
      of clinical donor variables.
AB  - BACKGROUND: Pre-implant biopsy findings account for the discard of many donor
      kidneys although their clinical value is not fully understood. We retrospectively
      investigated the predictive value of pre-implant histology, which in our center
      was obtained for protocol purposes, not for transplant decisions, on long-term
      allograft and recipient outcome after single-kidney transplantation. METHODS:
      This single-center study included 628 consecutive adult recipients of 174
      Expanded Criteria Donor (ECD) and 454 Standard Criteria Donor kidneys. Chronic
      donor organ injury was assessed applying a chronic lesion score differentiating
      between mild, moderate, and severe histologic organ injury based on the
      integration of glomerular, vascular, tubular, and interstitial lesions.
      Recipients were followed over a median time of 7.8 years. RESULTS: Donor kidneys
      exhibiting mild or moderate chronic lesions yielded almost identical graft and
      recipient survival independent of ECD status or other clinical covariables (HR
      1.20, 95% CI 0.83-1.74, P=0.326, and HR 1.27, 95% CI 0.83-1.95, P=0.274,
      respectively). However, if allograft injury was severe, occurring in 3% of
      transplanted kidneys, graft and recipient survival was significantly reduced (HR
      3.13, 95% CI 1.61-6.07, P<0.001 and HR 2.42, 95% CI 1.16-5.04, P=0.005,
      respectively). CONCLUSION: The results suggest that donor kidneys displaying
      moderate chronic injury can safely be transplanted as single kidneys, while
      organs displaying severe injury should be discarded. Thus, pre-implant biopsy
      might offer an effective approach to increase the utilization of renal donor
      organs, especially from ECD and donors with cerebrovascular accident as cause of
      death, and to improve overall graft outcome.

PMID- 24285341
TI  - Unanswered questions and research priorities to optimise stroke prevention in
      atrial fibrillation with the new oral anticoagulants.
AB  - This review article discusses the following, as yet unanswered, questions and
      research priorities to optimise patient management and stroke prevention in
      atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In
      patients prescribed a NOAC, can the anticoagulant effects or plasma
      concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut
      off points" between which anticoagulation is therapeutic (i.e. the "therapeutic
      range") be defined? 2. In patients who are taking a NOAC and bleeding (e.g.
      intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be
      reversed rapidly and, if so, can NOAC-associated bleeding and complications be
      minimised and patient outcome improved? 3. In patients taking a NOAC who
      experience an acute ischaemic stroke, to what degree of anticoagulation or plasma
      concentration of NOAC, if any, can thrombolysis be administered safely and
      effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is
      the optimal time to start (or re-start) anticoagulation with a NOAC (or
      warfarin)? 5. In anticoagulated patients who experience an intracranial
      haemorrhage, can anticoagulation with a NOAC be re-started safely and
      effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid
      geriatric people (who commonly have atrial fibrillation and are at high risk of
      stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the
      established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is
      there a dose or dosing regimen for each NOAC that is as effective and safe as
      adjusted-dose warfarin for patients with atrial fibrillation who have mechanical
      prosthetic heart valves? 9. What is the long-term safety of the NOACs? 

PMID- 24285342
TI  - The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and
      correlates with poor prognosis.
AB  - Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer.
      Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR), a long non-coding
      RNA (lncRNA), is associated with a variety of human cancers, such as breast,
      liver and lung cancer. However, whether HOTAIR can function as a molecular marker
      in endometrial carcinoma (EC) remains unknown. In the present study, the
      expression of HOTAIR in 66 EC tissues from patients with EC and 30 normal tissues
      from healthy age-matched control subjects was determined using quantitative
      reverse transcription PCR. Furthermore, using in situ hybridization, we measured
      HOTAIR expression in 129 formalin-fixed paraffin-embedded (FFPE) tissue sections,
      which included 96 tissues that matched the frozen cases, 21 other EC tissues and
      12 atypical hyperplasia tissues. Correlations between HOTAIR expression and the
      clinicopathological characteristics of patients were analyzed. Our results
      revealed that HOTAIR expression in the EC tissues was significantly upregulated
      compared with normal tissues (p<0.001). In addition, we observed a significant
      association between HOTAIR expression and the EC grade (p<0.05) and lymph node
      metastasis (p<0.05). Moreover, in the FFPE tissues, but not the frozen tissues,
      we found that a higher HOTAIR expression also correlated with the depth of
      myometrial invasion (p=0.019) and lymphovascular space invasion (p=0.015). More
      importantly, patients with a higher HOTAIR expression showed significantly poorer
      overall survival than those with lower HOTAIR expression (p<0.05). In conclusion,
      our results suggest that a high expression of HOTAIR is involved in the
      progression of cancer and may be a novel biomarker of poor prognosis in patients
      with EC.

PMID- 24285343
TI  - Mammalian Mon2/Ysl2 regulates endosome-to-Golgi trafficking but possesses no
      guanine nucleotide exchange activity toward Arl1 GTPase.
AB  - Arl1 is a member of Arf family small GTPases that is essential for the
      organization and function of Golgi complex. Mon2/Ysl2, which shares significant
      homology with Sec7 family Arf guanine nucleotide exchange factors, was poorly
      characterized in mammalian cells. Here, we report the first in depth
      characterization of mammalian Mon2. We found that Mon2 localized to trans-Golgi
      network which was dependent on both its N and C termini. The depletion of Mon2
      did not affect the Golgi localized or cellular active form of Arl1. Furthermore,
      our in vitro assay demonstrated that recombinant Mon2 did not promote guanine
      nucleotide exchange of Arl1. Therefore, our results suggest that Mon2 could be
      neither necessary nor sufficient for the guanine nucleotide exchange of Arl1. We
      demonstrated that Mon2 was involved in endosome-to-Golgi trafficking as its
      depletion accelerated the delivery of furin and CI-M6PR to Golgi after
      endocytosis. 

PMID- 24285344
TI  - Transport characteristics and transporter-based drug-drug interactions of TM
      25659, a novel TAZ modulator.
AB  - The in vitro metabolic stability and transport mechanism of TM-25659, a novel TAZ
      modulator, was investigated in human hepatocytes and human liver microsomes
      (HLMs) based on the preferred hepatobiliary elimination in rats. In addition, the
      in vitro transport mechanism and transporter-mediated drug-drug interactions were
      evaluated using oocytes and MDCKII cells overexpressing clinically important drug
      transporters. After a 1 h incubation in HLMs, 92.9 +/- 9.5% and 95.5 +/- 11.6% of
      the initial TM-25659 remained in the presence of NADPH and UDPGA, respectively.
      Uptake of TM-25659 readily accumulated in human hepatocytes at 37 oC (i.e. 6.7
      fold greater than that at 4 oC), in which drug transporters such as OATP1B1 and
      OATP1B3 were involved. TM-25659 had a significantly greater basal to apical
      transport rate (5.9-fold) than apical to basal transport rate in the Caco-2 cell
      monolayer, suggesting the involvement of an efflux transport system. Further
      studies using inhibitors of efflux transporters and overexpressing cells revealed
      that MRP2 was involved in the transport of TM-25659. These results, taken
      together, suggested that TM-25659 can be actively influxed into hepatocytes and
      undergo biliary excretion without substantial metabolism. Additionally, TM-25659
      inhibited the transport activities of OATP1B1 and OATP1B3 with IC50 values of
      36.3 and 25.9 MUm, respectively. TM-25659 (100 MUm) increased the accumulation of
      the probe substrate by 160% and 213%, respectively, through the inhibition of
      efflux function of P-gp and MRP2. In conclusion, OATP1B1, OATP1B3, P-gp and MRP2
      might be major transporters responsible for the pharmacokinetics and drug-drug
      interaction of TM-25659, although their contribution to in vivo pharmacokinetics
      needs to be further investigated.

PMID- 24285345
TI  - Incident cancer risk after the start of aspirin use: results from a Dutch
      population-based cohort study of low dose aspirin users.
AB  - Observational and intervention studies suggest that low dose aspirin use may
      prevent cancer. The objective of this study was to investigate the protective
      effect of long term low dose aspirin use (<=100 mg daily) on cancer in general
      and site-specific cancer among low dose aspirin users in the Dutch general
      population. We conducted a population-based cohort study with detailed
      information on aspirin exposure and cancer incidence. Only incident (new) low
      dose aspirin users, who were included in the linkage between PHARMO and the
      Eindhoven Cancer Registry (1998-2010) and free of cancer before the start of
      follow up were included. A Cox proportional hazard model with cumulative aspirin
      use as a time-varying determinant was used to obtain hazard ratios (HR). Duration
      of aspirin use amongst 109,276 incident low dose aspirin users was not associated
      with a decreased risk of any of the site-specific cancers or cancer in general
      (adjusted HR per year of aspirin use for all cancers: 1.02, 95% confidence
      interval [CI] 1.00-1.04, HR of >6 years aspirin use compared to <2 years: 1.17,
      95% CI 1.02-1.34). After adjusting for current and past aspirin use, 2-6 years of
      low dose aspirin use was associated with a reduced colorectal cancer risk
      compared to <2 years of aspirin use (adjusted HR 0.75, 95% CI 0.59-0.96).
      However, a clear dose-response relationship was not observed (adjusted HR >6
      years aspirin use 0.95, 95% CI 0.60-1.49). Our results do not support the primary
      prevention of cancer among long term aspirin users. 

PMID- 24285347
TI  - Synthesis and characterization of NpCl4(DME)2 and PuCl4(DME)2 neutral transuranic
      An(IV) starting materials.
AB  - The 1,2-dimethoxyethane (DME) solvento adducts of Np(iv) and Pu(iv) tetrachloride
      have been prepared and isolated in good and moderate yields, respectively, along
      with single-crystal structural determinations. These neutral molecules are
      expected to provide alternative synthetic pathways in the pursuit of non-aqueous
      and organometallic complexes. 

PMID- 24285348
TI  - Well-defined metal-organic framework hollow nanocages.
AB  - Metal-organic frameworks (MOFs) have demonstrated great potentials in a variety
      of important applications. To enhance the inherent properties and endow materials
      with multifunctionality, the rational design and synthesis of MOFs with nanoscale
      porosity and hollow feature is highly desired and remains a great challenge. In
      this work, the formation of a series of well-defined MOF (MOF-5, Fe(II) -MOF-5,
      Fe(III) -MOF-5) hollow nanocages by a facile solvothermal method, without any
      additional supporting template is reported. A surface-energy-driven mechanism may
      be responsible for the formation of hollow nanocages. The addition of pre
      synthesized poly(vinylpyrrolidone)- (PVP) capped noble-metal nanoparticles into
      the synthetic system of MOF hollow nanocages yields the yolk-shell noble
      metal@MOF nanostructures. The present strategy to fabricate hollow and yolk-shell
      nanostructures is expected to open up exciting opportunities for developing a
      novel class of inorganic-organic hybrid functional nanomaterials. 

PMID- 24285349
TI  - Short and medium-term therapeutic effects of pneumatic dilatation for achalasia:
      a 15-year tertiary centre experience.
AB  - BACKGROUND: Pneumatic dilatation (PD) is a commonly used endoscopic technique to
      weaken the lower oesophageal sphincter in patients with achalasia. It is
      considered as the most effective non-surgical therapeutic option for achalasia,
      but further data on the overall effectiveness and rate of complications is
      needed. AIMS: To determine the short- and medium-term therapeutic effectiveness
      of PD for achalasia and estimate the cumulative probability of remaining in
      remission over one year after a single treatment. The study also aimed to
      identify clinical predictors of therapeutic outcome achieved by PD and assess for
      PD-related complications. METHODS: A total of 26 patients with achalasia who were
      treated with PD between 1997 and 2011 at a tertiary care centre were followed for
      up to 1 year. Data related to demographics, clinical symptoms and PD-related
      complications were collected. Short (1 and 3 months) and medium (1 year) term
      therapeutic effectiveness of PD was assessed with the use of the Eckhart scoring
      system for evaluation of clinical symptoms. The probability of staying in
      remission one year after a single PD was determined by using a Kaplan-Meier
      estimator. In order to prevent major complications, limited maximal pressure of
      no more than 11 PSI was used during PD. RESULTS: Twenty-six patients with
      symptomatic achalasia (mean age 47.1+/-18.5 years, 82% males) underwent 44 PD
      procedures (mean 1.7/patient). Thirteen patients (50%) had a single PD, 10
      patients (38%) had two dilatations, and 3 patients (12%) had three or more
      dilatations over one year. Nineteen out of the 26 patients (73%) were in
      remission at one and three months each, following the initial PD. Seventeen out
      of the 26 patients (65%) remained in remission after one year. A total of 5
      patients (19%) were referred for surgery over 1 year due to lack of success of
      the endoscopic treatment. The mean Eckhart symptom scores, at 1 month (3.2+/
      1.2), 3 months (3.5+/-1.3) and 1 year (1.8+/-0.6) after the initial PD, were
      significantly lower when compared to the mean initial Eckhart symptom score
      (9.7+/-4.4, P<0.05). Using a symptom score above 3 as a cutoff value for
      treatment failure, the probability of remaining in remission (relapse-free) after
      a single dilatation was 35% at one year. Patient gender appeared as an important
      treatment outcome predictor. Namely, 4 of the 5 patients (80%) with PD treatment
      failure were males. There were no major complications from the 44 PDs. One
      patient (3.8%) developed significant heartburn. The majority of PDs (33/44, 75%)
      were followed with minor, subclinical oesophageal mucosal bleeding from the
      dilation site as seen on post-dilation oesophagoscopy. CONCLUSION: Pneumatic
      dilatation is an effective short and medium term treatment option for the
      majority of patients with achalasia without significant related complications.
      Further studies are warranted to assess the possible role of limited maximal
      pressure use of no more than 11 PSI during PD in preventing oesophageal
      perforations.

PMID- 24285346
TI  - Parsing dimensional vs diagnostic category-related patterns of reward circuitry
      function in behaviorally and emotionally dysregulated youth in the Longitudinal
      Assessment of Manic Symptoms study.
AB  - IMPORTANCE: Pediatric disorders characterized by behavioral and emotional
      dysregulation pose diagnostic and treatment challenges because of high
      comorbidity, suggesting that they may be better conceptualized dimensionally
      rather than categorically. Identifying neuroimaging measures associated with
      behavioral and emotional dysregulation in youth may inform understanding of
      underlying dimensional vs disorder-specific pathophysiologic features. OBJECTIVE:
      To identify, in a large cohort of behaviorally and emotionally dysregulated
      youth, neuroimaging measures that (1) are associated with behavioral and
      emotional dysregulation pathologic dimensions (behavioral and emotional
      dysregulation measured with the Parent General Behavior Inventory 10-Item Mania
      Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic
      categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder,
      anxiety, and disruptive behavior disorders). DESIGN, SETTING, AND PARTICIPANTS: A
      multisite neuroimaging study was conducted from February 1, 2011, to April 15,
      2012, at 3 academic medical centers: University Hospitals Case Medical Center,
      Cincinnati Children's Hospital Medical Center, and University of Pittsburgh
      Medical Center. Participants included a referred sample of behaviorally and
      emotionally dysregulated youth from the Longitudinal Assessment of Manic Symptoms
      (LAMS) study (n = 85) and healthy youth (n = 20). MAIN OUTCOMES AND MEASURES:
      Region-of-interest analyses examined relationships among prefrontal-ventral
      striatal reward circuitry during a reward paradigm (win, loss, and control
      conditions), symptom dimensions, and diagnostic categories. RESULTS: Regardless
      of diagnosis, higher PGBI-10M scores were associated with greater left middle
      prefrontal cortical activity (r = 0.28) and anxiety with greater right dorsal
      anterior cingulate cortical (r = 0.27) activity to win. The 20 highest (t = 2.75)
      and 20 lowest (t = 2.42) PGBI-10M-scoring youth showed significantly greater left
      middle prefrontal cortical activity to win compared with 20 healthy youth.
      Disruptive behavior disorders were associated with lower left ventrolateral
      prefrontal cortex activity to win (t = 2.68) (all P < .05, corrected).
      CONCLUSIONS AND RELEVANCE: Greater PGBI-10M-related left middle prefrontal
      cortical activity and anxiety-related right dorsal anterior cingulate cortical
      activity to win may reflect heightened reward sensitivity and greater attention
      to reward in behaviorally and emotionally dysregulated youth regardless of
      diagnosis. Reduced left ventrolateral prefrontal cortex activity to win may
      reflect reward insensitivity in youth with disruptive behavior disorders. Despite
      a distinct reward-related neurophysiologic feature in disruptive behavior
      disorders, findings generally support a dimensional approach to studying neural
      mechanisms in behaviorally and emotionally dysregulated youth.

PMID- 24285350
TI  - Evaluation of a rotavirus acute gastroenteritis severity score in hospitalized
      children over a ten year period in a clinic of infectious diseases, Skopje, R.
      Macedonia.
AB  - Rotavirus infection is the most common viral infection of the gastrointestinal
      tract in children with the most severe clinical manifestations and rapidly
      progressive dehydration, especially in infancy and early childhood. Due to its
      characteristics of high contagiousness and being widespread in both developed
      countries and developing countries with a still high fatality rate, active
      prevention of the disease is recognized as the only successful measure for
      preventing severe forms of the disease. The assessment of the severity of the
      clinical picture with the corresponding severity scales, Vesikari or Clark, is
      essential for interpretation of the success of the applied vaccine. THE PURPOSE
      OF THE STUDY: A ten-year review of the frequency of appearance and laboratory
      features of Rotavirus Gastroenteritis in Paediatrics at the Infectious Diseases
      Clinic, Skopje, Macedonia. The goal of the study is to stress the constant
      presence of infection with severe clinical manifestations and the necessity of
      the introduction of vaccination. MATERIALS AND METHODS: Acute viral
      gastoenteritis patients were processed, whose clinical presentation indicated
      mandatory hospitalization. Biochemical laboratory parameters were required for
      all children, and they were grouped in appropriate severity groups depending on
      the values of the clinical parameters on the Vesikari and Clark scales. By taking
      a biochemical laboratory analysis using statistical methods we searched for an
      answer to whether and to what extent their values are predictive for assessment
      of the severity of the disease, and how much they influence the values in each of
      the scales. RESULTS: 1012 children at an average age of 19.51 months, treated
      from 2003 to 2012, tested with 12 parameters and grouped into scales, showed the
      existence of a correlation between the scales of 0.8277. Processing our results
      suggests the use of a modified Vesikari scale for clinical assessment of disease
      severity, and thus the ability to monitor the effectiveness of vaccination.

PMID- 24285351
TI  - Anaemia and inflammatory bowel disease.
AB  - BACKGROUND: Anaemia has been recognised as a key symptom of IBD. Although
      efficient therapeutic options have been developed for the treatment of IBD
      associated anaemia, treating anaemia often has a low priority for
      gastroenterologists. Compared with other manifestations of the disease, such as
      arthritis or osteopathy, anaemia in IBD has been given scant attention. AIM: To
      evaluate prevalence of anaemia in patients treated for IBD in the Department of
      Gastroenterology and Hepatology, Clinical Centre, University of Sarajevo.
      PATIENTS AND METHODS: The study was conducted between January 2010 and November
      2012 as a retrospective observational clinical trial. Total of 210 patients were
      recruited. All patients with histopatological verification of IBD were divided
      into three groups, according to CDAI (Chronic Disease Activity Index):
      Biochemical parameters were recorded: full blood count, haemoglobin, haematocrit,
      RBC, WBC, proteinogram, fibrinogen, CRP. RESULTS: Most of patients had
      haemoglobin serum level in range 100-120 g/l. Lower haemoglobin serum levels were
      measured in 40% of pts (CDAI>220). Lower haematocrit levels were detected in 38%
      of subjects with verified IBD ( CDAI>220). In the comparison of haematocrit level
      in the group of patients with CDAI>220 (moderate activity: 220-450 and high
      activity: >450) and CDAI<220 (low activity: 150-220) the statistical difference
      was at level p<0.04. In the comparison of haemoglobin level in the group of
      patients with moderate or high activity and low activity, by Student t-test the
      statistical difference was at level p<0.03. Hypoalbuminaemia was detected in
      37.6% of patients. A significantly lower albumin level was in the group of
      moderate and high activity of IBD, at p<0.05 (ANOVA). Increased parameters of
      inflammation (CRP, fibrinogen and SE) were present in 35% of cases. CONCLUSION:
      Anaemia could be the most common systemic complication of acute IBD. In our study
      40 % of patients with IBD had anaemia; increased parameters of inflammation were
      present in 35% of cases. The control of inflammation is a key point, but often is
      not enough to treat anaemia. Patients should be followed up after completing
      treatment, and anaemia and iron deficiency actively assessed in the standard
      investigations.

PMID- 24285352
TI  - Conversions in laparoscopic cholecystectomy in acute versus chronic
      cholecystitis.
AB  - BACKGROUND: Early laparoscopic cholecystectomy imposes itself as an option of
      choice for treatment of acute cholecystitis, while the rate of conversions to
      open procedure represents a key parameter for evaluating the outcome. AIM: The
      aim of this paper was to evaluate the results of the laparoscopic cholecystectomy
      in acute versus chronic cholecystitis through determining the conversion rate in
      open method, as well as to analye some predictive factors that may impact the
      decision to convert to open. MATERIAL AND METHODS: An analytical case control
      study was conducted at the University Clinic for Digestive Surgery in Skopje
      within a period of 27 months. The first group included 62 patients with acute
      cholecystitis on whom the laparoscopic cholecystectomy was performed in the
      period from zero to the seventh day from the onset of symptoms. The second group
      included 62 patients with chronic cholecystitis who underwent laparoscopic
      cholecystectomy. Gender, age, history of cholecystitis, the time passed from the
      first symptoms till laparoscopic cholecystectomy and the duration of the
      intervention were analysed as factors that can possibly act on conversion.
      RESULTS: There were no significant differences (p>0.05) between the group of
      patients with acute and the one with chronic cholecystitis due to conversion
      rate. In both groups, there was a significant difference in conversion due to the
      duration of the laparoscopic cholecystectomy (p<0.05), and in the group with
      acute cholecystitis also due to the time passed from the first symptoms till the
      laparoscopic intervention (p<0.01). CONCLUSION: The rate of conversions can be
      reduced with a prompt approach to predictive factors.

PMID- 24285353
TI  - Laboratory surveillance during pandemic influenza season 2009/2010 in Republic of
      Macedonia.
AB  - OBJECTIVE: To provide virological and epidemiological information on patients
      laboratory-tested for influenza A/ H1N1pdm during the pandemic season April
      2009/May 2010. MATERIALS AND METHODS: Demographic and other data were obtained
      from the request form arriving with the samples of patients whose symptoms met
      the clinical definition of influenza A infection. The RNA was tested for the
      presence of influenza virus using the CDC real-time RT-PCR assay. A total of 3010
      suspect patients (pts) were tested from week 18 2009 to week 20 2010. RESULTS:
      1632 pts (54.2%) were oositive for influenza. From them 1556 samples were
      confirmed as H1N1pdm. There was a domination of H1N1pdm positivity among young
      persons in age groups 5-17 (34.4%) and 18-49 (31.4%) years. The pandemic
      influenza was presented in two waves. The first wave started on 20 June with the
      first positive case and peaked early in August (week 32). The second wave started
      from week 44. The majority of positive cases were between week 45 and week 52.
      37.7% of the positive pts were hospitalized--66.7% of pts at age 65+ and 63.3% of
      children in the age group 0-4 years. The highest percentage of patients with
      underlying medical conditions were in the age group 50-64 (49.35%) years and 65+
      (88.23%) years. 1.15% of the positive pts for H1N1pdm gave data for vaccination
      with seasonal influenza. CONCLUSIONS: Data obtained from laboratory and
      epidemiological surveillance of pandemic influenza will serve public health to a
      full understanding of the pandemic 2009/2010 influenza in R. Macedonia and
      dealing with future challenges.

PMID- 24285354
TI  - Acacetin (5,7-dihydroxy-4'-methoxyflavone) exhibits in vitro and in vivo
      anticancer activity through the suppression of NF-kappaB/Akt signaling in
      prostate cancer cells.
AB  - Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a flavonoid compound with
      antimutagenic, antiplasmodial, antiperoxidant, anti-inflammatory and anticancer
      effects. However, the molecular targets and pathways underlying the anticancer
      effects of acacetin are yet to be elucidated. In this study, we investigated
      whether acacetin induces apoptosis in the human prostate cancer cell line, DU145.
      The results of 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assays revealed that cell viability decreased in a dose- and time-dependent
      manner in response to acacetin. 4',6-Diamidino-2-phenylindole (DAPI) staining
      revealed that chromatin condensation significantly increased in a dose-dependent
      manner. Flow cytometric analysis indicated that acacetin suppressed the viability
      of DU145 cells by inducing apoptosis. Western blot anlaysis of various markers of
      signaling pathways revealed that acacetin targets the Akt and nuclear factor (NF)
      kappaB signaling pathways by inhibiting the phosphorylation of IkappaBalpha and
      NF-kappaB in a dose-dependent manner. Consistent with its ability to induce
      apoptosis, the acacetin-mediated inhibition of the pro-survival pathway, Akt, and
      of the NF-kappaB pathway was accompanied by a marked reduction in the levels of
      the NF-kappaB-regulated anti-apoptotic proteins, Bcl-2 and X-linked inhibitor of
      apoptosis protein (XIAP), as well as of the proliferative protein, cyclooxygenase
      (COX)-2. We further evaluated the effects of acacetin on prostate cancer using
      mice subcutaneously injected with DU145 prostate cancer cells. The acacetin
      treated nude mice bearing DU145 tumor xenografts exhibited significantly reduced
      tumor size and weight, due to the effects of acacetin on cancer cell apoptosis,
      as determined by terminal deoxyribonucleotide transferase-mediated dUTP nick end
      labeling (TUNEL) assay. Our findings suggest that acacetin exerts antitumor
      effects by targeting the Akt/NF-kappaB signaling pathway. Rurther investigations
      on this flavonoid are warranted to evaluate its potential use in the prevention
      and therapy of prostate cancer.

PMID- 24285355
TI  - The elusive disconnection between mortality and early stent thrombosis:
      observations from the CHAMPION-PHOENIX trial.

PMID- 24285356
TI  - From diphosphino-functionalized 1,3-dialkylimidazolium cations to imidazolones
      through dehydrogenative C-N coupling.
AB  - Diphosphino-functionalized 1,3-dialkylimidazolium salts react with KOH affording
      amine/formamide open-chain products, which fully revert to the imidazolium cation
      by treatment with a variety of acids or are converted to 2-imidazolones by
      noncatalyzed intramolecular dehydrogenative C-N coupling, a process that is
      modulated by coordination of the phosphino functionalities to transition metals.

PMID- 24285358
TI  - Observation of adsorption versus depletion interaction for charged silica
      nanoparticles in the presence of non-ionic surfactant.
AB  - The interaction of anionic silica nanoparticles (Ludox LS30) with non-ionic
      surfactant decaethylene glycol monododecylether (C12E10) without and in the
      presence of an electrolyte has been studied by small-angle neutron scattering
      (SANS) and dynamic light scattering (DLS). The measurements have been carried out
      for fixed concentrations of nanoparticles (1 wt%), surfactant (1 wt%) and
      electrolyte (0.1 M NaCl). In SANS, each of these nanoparticle-surfactant systems
      has been examined for three different contrast conditions where both
      (nanoparticle and surfactant) as well as individual components (nanoparticle or
      surfactant) are made visible. It is observed that the nanoparticle-surfactant
      systems behave very differently without and with the electrolyte. In the absence
      of salt, the C12E10 micelles form micelle decorated core-shell structures by
      adsorbing on the nanoparticles. On the other hand, the adsorption of surfactant
      micelles on nanoparticle is completely suppressed in the presence of salt,
      leading to the depletion-induced aggregation of nanoparticles. These results have
      also been corroborated by the DLS data. We thus show that the ionic strength of
      solution can be used to tune the interaction of ionic silica nanoparticles with
      non-ionic surfactant. 

PMID- 24285359
TI  - Fitness and stability of obligate cross-feeding interactions that emerge upon
      gene loss in bacteria.
AB  - Cross-feeding interactions, in which bacterial cells exchange costly metabolites
      to the benefit of both interacting partners, are very common in the microbial
      world. However, it generally remains unclear what maintains this type of
      interaction in the presence of non-cooperating types. We investigate this problem
      using synthetic cross-feeding interactions: by simply deleting two metabolic
      genes from the genome of Escherichia coli, we generated genotypes that require
      amino acids to grow and release other amino acids into the environment.
      Surprisingly, in a vast majority of cases, cocultures of two cross-feeding
      strains showed an increased Darwinian fitness (that is, rate of growth) relative
      to prototrophic wild type cells--even in direct competition. This unexpected
      growth advantage was due to a division of metabolic labour: the fitness cost of
      overproducing amino acids was less than the benefit of not having to produce
      others when they were provided by their partner. Moreover, frequency-dependent
      selection maintained cross-feeding consortia and limited exploitation by non
      cooperating competitors. Together, our synthetic study approach reveals
      ecological principles that can help explain the widespread occurrence of obligate
      metabolic cross-feeding interactions in nature.

PMID- 24285360
TI  - Moderate changes in nutrient input alter tropical microbial and protist
      communities and belowground linkages.
AB  - We investigated the response of soil microbial communities in tropical ecosystems
      to increased nutrient deposition, such as predicted by anthropogenic change
      scenarios. Moderate amounts of nitrogen and phosphorus and their combination were
      added along an altitudinal transect. We expected microorganisms and microbial
      grazers (testate amoebae) to significantly respond to nutrient additions with the
      effect increasing with increasing altitude and with duration of nutrient
      additions. Further, we expected nutrients to alter grazer-prey
      interrelationships. Indeed, nutrient additions strongly altered microbial biomass
      (MB) and community structure as well as the community structure of testate
      amoebae. The response of microorganisms varied with both altitude and duration of
      nutrient addition. The results indicate that microorganisms are generally limited
      by N, but saprotrophic fungi also by P. Also, arbuscular mycorrhizal fungi
      benefited from N and/or P addition. Parallel to MB, testate amoebae benefited
      from the addition of N but were detrimentally affected by P, with the addition of
      P negating the positive effect of N. Our data suggests that testate amoeba
      communities are predominantly structured by abiotic factors and by antagonistic
      interactions with other microorganisms, in particular mycorrhizal fungi, rather
      than by the availability of prey. Overall, the results suggest that the
      decomposer system of tropical montane rainforests significantly responds to even
      moderate changes in nutrient inputs with the potential to cause major
      ramifications of the whole ecosystem including litter decomposition and plant
      growth. 

PMID- 24285361
TI  - Metabolic analysis of Chlorobium chlorochromatii CaD3 reveals clues of the
      symbiosis in 'Chlorochromatium aggregatum'.
AB  - A symbiotic association occurs in 'Chlorochromatium aggregatum', a phototrophic
      consortium integrated by two species of phylogenetically distant bacteria
      composed by the green-sulfur Chlorobium chlorochromatii CaD3 epibiont that
      surrounds a central beta-proteobacterium. The non-motile chlorobia can perform
      nitrogen and carbon fixation, using sulfide as electron donors for anoxygenic
      photosynthesis. The consortium can move due to the flagella present in the
      central beta-protobacterium. Although Chl. chlorochromatii CaD3 is never found as
      free-living bacteria in nature, previous transcriptomic and proteomic studies
      have revealed that there are differential transcription patterns between the
      symbiotic and free-living status of Chl. chlorocromatii CaD3 when grown in
      laboratory conditions. The differences occur mainly in genes encoding the
      enzymatic reactions involved in nitrogen and amino acid metabolism. We performed
      a metabolic reconstruction of Chl. chlorochromatii CaD3 and an in silico analysis
      of its amino acid metabolism using an elementary flux modes approach (EFM). Our
      study suggests that in symbiosis, Chl. chlorochromatii CaD3 is under limited
      nitrogen conditions where the GS/GOGAT (glutamine synthetase/glutamate
      synthetase) pathway is actively assimilating ammonia obtained via N2 fixation. In
      contrast, when free-living, Chl. chlorochromatii CaD3 is in a condition of
      nitrogen excess and ammonia is assimilated by the alanine dehydrogenase (AlaDH)
      pathway. We postulate that 'Chlorochromatium aggregatum' originated from a
      parasitic interaction where the N2 fixation capacity of the chlorobia would be
      enhanced by injection of 2-oxoglutarate from the beta-proteobacterium via the
      periplasm. This consortium would have the advantage of motility, which is
      fundamental to a phototrophic bacterium, and the syntrophy of nitrogen and carbon
      sources. 

PMID- 24285362
TI  - Mass spectrometry analysis of nucleosides and nucleotides.
AB  - Mass spectrometry has been widely utilised in the study of nucleobases,
      nucleosides and nucleotides as components of nucleic acids and as bioactive
      metabolites in their own right. In this review, the application of mass
      spectrometry to such analysis is overviewed in relation to various aspects
      regarding the analytical mass spectrometric and chromatographic techniques
      applied and also the various applications of such analysis.

PMID- 24285363
TI  - A mathematical model of long-term renal sympathetic nerve activity inhibition
      during an increase in sodium intake.
AB  - It is well known that renal nerves directly affect renal vascular resistance,
      tubular sodium reabsorption, and renin secretion. Inhibition of renal sympathetic
      nerve activity (RSNA) decreases renal vascular resistance, tubular sodium
      reabsorption, and renin secretion, leading to an increase in sodium excretion.
      Although several studies show that inhibition of RSNA promotes sodium excretion
      during an acute blood volume expansion, there is limited research relating to the
      importance of RSNA inhibition that contributes to sodium homeostasis during a
      long-term increase in sodium intake. Therefore, to dissect the underlying
      mechanisms of sodium excretion, a mathematical model of a cardiovascular system
      consisting of two kidneys, each with an independent RSNA, was developed.
      Simulations were performed to determine the responses of RSNA and sodium
      excretion to an increased sodium intake. In these simulations, RSNA in the left
      kidney was fixed at its normal steady-state value, while RSNA in the
      contralateral kidney was allowed to change normally in response to the increased
      sodium intake. The results demonstrate that the fixed-RSNA kidney excretes less
      sodium than the intact-RSNA collateral kidney. Because each kidney is exposed to
      the same arterial pressure and circulatory hormones, the impaired sodium
      excretion in the absence of RSNA inhibition supports the hypothesis that RSNA
      inhibition contributes to natriuresis in response to a long-term increase in
      sodium intake. 

PMID- 24285364
TI  - Phosphorylation of myosin regulatory light chain has minimal effect on kinetics
      and distribution of orientations of cross bridges of rabbit skeletal muscle.
AB  - Force production in muscle results from ATP-driven cyclic interactions of myosin
      with actin. A myosin cross bridge consists of a globular head domain, containing
      actin and ATP-binding sites, and a neck domain with the associated light chain 1
      (LC1) and the regulatory light chain (RLC). The actin polymer serves as a "rail"
      over which myosin translates. Phosphorylation of the RLC is thought to play a
      significant role in the regulation of muscle relaxation by increasing the degree
      of skeletal cross-bridge disorder and increasing muscle ATPase activity. The
      effect of phosphorylation on skeletal cross-bridge kinetics and the distribution
      of orientations during steady-state contraction of rabbit muscle is investigated
      here. Because the kinetics and orientation of an assembly of cross bridges (XBs)
      can only be studied when an individual XB makes a significant contribution to the
      overall signal, the number of observed XBs was minimized to ~20 by limiting the
      detection volume and concentration of fluorescent XBs. The autofluorescence and
      photobleaching from an ex vivo sample was reduced by choosing a dye that was
      excited in the red and observed in the far red. The interference from scattering
      was eliminated by gating the signal. These techniques decrease large
      uncertainties associated with determination of the effect of phosphorylation on a
      few molecules ex vivo with millisecond time resolution. In spite of the remaining
      uncertainties, we conclude that the state of phosphorylation of RLC had no effect
      on the rate of dissociation of cross bridges from thin filaments, on the rate of
      myosin head binding to thin filaments, and on the rate of power stroke. On the
      other hand, phosphorylation slightly increased the degree of disorder of active
      cross bridges. 

PMID- 24285365
TI  - Multifunctional polypyrrole@Fe(3)O(4) nanoparticles for dual-modal imaging and in
      vivo photothermal cancer therapy.
AB  - Magnetic Fe3 O4 crystals are produced in situ on preformed polypyrrole (PPY)
      nanoparticles by rationally converting the residual Fe species in the synthetic
      system. The obtained PPY@Fe(3)O(4)composite nanoparticles exhibit good
      photostability and biocompatibility, and they can be used as multifunctional
      probes for MRI, thermal imaging, and photothermal ablation of cancer cells.

PMID- 24285366
TI  - Anterior referencing versus posterior referencing in total knee arthroplasty.
AB  - Appropriate femoral component positioning and sizing is essential for proper
      kinematic function in total knee arthroplasty (TKA). Anterior or posterior
      referencing (AR or PR) are two major techniques for setting center of rotation
      and for balancing the sagittal plane of the arthroplasty. Both techniques have
      advantages and disadvantages. Minimally invasive surgical (MIS) TKA has added yet
      another aspect to intraoperative techniques and postoperative outcomes. A total
      of 100 consecutive patients undergoing unilateral MIS TKA were prospectively
      randomized to either AR or PR. Knee Society Scores, range of motion, SF-12, and
      strength testing by Cybex dynamometer were evaluated at standardized intervals
      postoperatively for 2 years. There were no statistically significant differences
      in surgical (incision length, surgical release, blood loss, surgical time, and
      length of stay) or clinical outcomes between two groups at all postoperative
      intervals (2 and 6 weeks, 3 and 6 months, and 1 and 2 years). Results demonstrate
      that both AR and PR are effective and can be used successfully during MIS TKA. 

PMID- 24285367
TI  - Incidence of associated knee injury in pediatric tibial eminence fractures.
AB  - Our intent is to review pediatric tibial eminence fractures treated at a Level I
      Trauma Center and to note the incidence of associated knee pathology. All
      pediatric patients treated operatively for a tibial eminence fracture over a 10
      year period were identified. A chart review was performed to identify patient
      demographics, injury pattern, presence of associated pathology, and magnetic
      resonance imaging (MRI) findings. In our series of 20 pediatric tibial eminence
      fractures, 6 patients had associated meniscal tears. Meniscal tears occurred more
      commonly in type III injuries (5 of 13) than type II injuries (1 of 6). Two
      patients sustained associated ligamentous injury; there were no patients with
      associated chondral defects. A displaced pediatric tibial eminence fracture is a
      relatively infrequent injury. The incidence of associated meniscal injury in our
      study was 30%, and associated ligamentous injury was uncommon. Arthroscopic
      evaluation before definitive treatment of displaced tibial eminence fractures
      should be considered given the associated incidence of meniscal tears. MRI does
      not appear to provide additional information if arthroscopic treatment is
      pursued. This study is level IV, case series.

PMID- 24285368
TI  - Confusion concerning multiple versions of the childhood myositis assessment
      scale.

PMID- 24285369
TI  - Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of
      diabetes patients in response to bacterial infection.
AB  - Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused
      by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear
      neutrophils (PMNs) from diabetic subjects exhibited decreased functions in
      response to B. pseudomallei. Here we investigated the mechanisms regulating
      cytokine secretion of PMNs from diabetic patients which might contribute to
      patient susceptibility to bacterial infections. Purified PMNs from diabetic
      patients who had been treated with glibenclamide (an ATP-sensitive potassium
      channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)
      1beta and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction
      of these pro-inflammatory cytokines occurred when PMNs from diabetic patients
      were treated in vitro with glibenclamide. These findings suggest that
      glibenclamide might be responsible for the increased susceptibility of diabetic
      patients, with poor glycemic control, to bacterial infections as a result of its
      effect on reducing IL-1beta production by PMNs. 

PMID- 24285370
TI  - Introducing Protocols and Methods.

PMID- 24285371
TI  - RGD-based PET tracers for imaging receptor integrin alphav beta3 expression.
AB  - Positron emission tomography (PET) imaging of receptor integrin alphav beta3
      expression may play a key role in the early detection of cancer and
      cardiovascular diseases, monitoring disease progression, evaluating therapeutic
      response, and aiding anti-angiogenic drugs discovery and development. The last
      decade has seen the development of new PET tracers for in vivo imaging of
      integrin alphav beta3 expression along with advances in PET chemistry. In this
      review, we will focus on the radiochemistry development of PET tracers based on
      arginine-glycine-aspartic acid (RGD) peptide, present an overview of general
      strategies for preparing RGD-based PET tracers, and review the recent advances in
      preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers,
      RGD-based PET multivalent probes, and RGD-based PET multimodality probes for
      imaging receptor integrin alphav beta3 expression. 

PMID- 24285372
TI  - Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal
      antibody targeting the epidermal growth factor receptor.
AB  - BACKGROUND: Radiolabelled monoclonal antibodies with affinity towards tumour
      associated antigens may enhance the efficacy of cancer treatment with targeted
      radiotherapy. The humanized antibody nimotuzumab represents a promising vector to
      deliver radioactivity to tumours overexpressing epidermal growth factor receptor
      type 1 (ErbB1). We analysed the effect of radiolabelling nimotuzumab on its
      uptake in cancer cells and its biodistribution profile in preclinical
      experiments. METHODS: Nimotuzumab was labelled with (131) I by oxidative
      iodination and with (177) Lu using nimotuzumab conjugates with two different
      chelators (DTPA and DOTA) and two different spacers (p-SCN-Bn and NHS). For the
      receptor studies, two cell lines (HaCaT and A431) were used. Biodistribution
      studies were performed in male Wistar rats. RESULTS: The choice of radiolabel and
      the manner of its attachment to nimotuzumab had little effect on the
      internalization of the antibody into ErbB1-expressing cell lines. However, the
      type of radiolabel, the way in which it was attached to nimotuzumab and the
      radiolabelling procedure, significantly affected the blood clearance, liver
      uptake and liver persistence of radiolabelled nimotuzumab. (131) I-nimotuzumab
      had the longest elimination half-life and the lowest radioactivity uptake in the
      liver. (177) Lu-labelled nimotuzumab exhibited a shorter elimination half-life,
      high radioactivity and long-term retention in the liver.

PMID- 24285373
TI  - Microfluidic radiosynthesis and biodistribution of [18 F] 2-(5-fluoro-pentyl)-2
      methyl malonic acid.
AB  - Microfluidics technology has emerged as a powerful tool for the radiosynthesis of
      positron emission tomography (PET) and single-photon emission computed tomography
      radiolabeled compounds. In this work, we have exploited a continuous flow
      microfluidic system (Advion, Inc., USA) for the [(18) F]-fluorine radiolabeling
      of the malonic acid derivative, [(18) F] 2-(5-fluoro-pentyl)-2-methyl malonic
      acid ([(18) F]-FPMA), also known as [(18) F]-ML-10, a radiotracer proposed as a
      potential apoptosis PET imaging agent. The radiosynthesis was developed using a
      new tosylated precursor. Radiofluorination was initially optimized by manual
      synthesis and served as a basis to optimize reaction parameters for the
      microfluidic radiosynthesis. Under optimized conditions, radio-thin-layer
      chromatography analysis showed 79% [(18) F]-fluorine incorporation prior to
      hydrolysis and purification. Following hydrolysis, the [(18) F]-FPMA was purified
      by C18 Sep-Pak, and the final product was analyzed by radio-HPLC (high
      performance liquid chromatography). This resulted in a decay-corrected 60%
      radiochemical yield and >=98% radiochemical purity. Biodistribution data
      demonstrated rapid blood clearance with less than 2% of intact [(18) F]-FPMA
      radioactivity remaining in the circulation 60 min post-injection. Most organs
      showed low accumulation of the radiotracer, and radioactivity was predominately
      cleared through kidneys (95% in 1 h). Radio-HPLC analysis of plasma and urine
      samples showed a stable radiotracer at least up to 60 min post-injection. 

PMID- 24285374
TI  - Preparation and stability of ethanol-free solution of [18F]florbetapir ([18F]AV
      45) for positron emission tomography amyloid imaging.
AB  - We have developed an ethanol-free formulation method of [(18) F]florbetapir ([(1)
      (8) F]AV-45) using a commercially available automated JFE multi-purpose
      synthesizer. We have also evaluated the radiochemical stability in an ethanol
      free solution of [(18) F]AV-45 under visible light irradiation and dark
      conditions by comparison with a conventional 10% ethanol solution of [(18) F]AV
      45. [(18) F]AV-45 was obtained with a radiochemical yield of 55.1 +/- 2.2% (decay
      corrected to end of bombardment), specific activity of 591.6 +/- 90.3 GBq/umol
      and radiochemical purity of >99% within a total synthesis time of about 73 min.
      The radiochemical purity of [(18) F]AV-45 formulated by dissolving the ethanol
      free solution was found to decrease as a function of the period of exposure to
      visible light. In contrast, the visible light photolysis could be suppressed by
      adding 10% ethanol to the formulation or by avoiding exposure to visible light.
      In the radiosynthesis of [(18) F]AV-45 formulated by dissolving the ethanol-free
      solution, [(18) F]AV-45 could be obtained with high radiochemical purity and high
      stability by avoiding exposure to visible light.

PMID- 24285375
TI  - Determination of the radiochemical purity of (99m) Tc medronate injection by thin
      layer chromatography on iTLC-SG: effect of medronate concentration on the value
      measured.
AB  - BACKGROUND: When using iTLC-SG thin layer chromatography plates to measure
      radiochemical impurities in (99m) Tc medronate, falsely high values were obtained
      for (99m) Tc pertechnetate impurity. Preliminary investigations indicated that
      the mass of (99m) Tc medronate applied to the plate influences the value. AIM:
      The goal of this study was to determine if the concentration of medronate
      influences the value obtained for (99m) Tc pertechnetate impurity. EXPERIMENTAL:
      (99m) Tc medronate was prepared at two concentrations: 4 mg/mL and 0.2 mg/mL.
      Impurity levels were measured using three stationary phases: dried and undried
      iTLC-SG and 54SFC paper. Two mobile phases were used: methyl ethyl ketone to
      detect (99m) Tc pertechnetate and sodium acetate 136 g/L to detect hydrolysed and
      colloidal (99m) Tc. Sample spot drying and volume were also investigated.
      RESULTS: With 4 mg/mL samples, the three stationary phases measured similar
      impurity levels (p > 0.05). With the 0.2 mg/mL samples, higher levels of (99m) Tc
      pertechnetate were measured with iTLC-SG than with paper (p < 0.05). Neither
      sample spot drying nor volume was found to affect impurity levels measured.
      CONCLUSIONS: When using iTLC-SG to measure the radiochemical purity of (99m) Tc
      medronate, an artefactually high level of (99m) Tc pertechnetate impurity is
      measured when the medronate concentration in the sample is low. The iTLC-SG
      stationary phase may be unsatisfactory for measuring the radiochemical purity of
      (99m) Tc medronate.

PMID- 24285376
TI  - Synthesis of C-13-labeled atrazine.
AB  - Atrazine is a long-lasting herbicide that has been shown to affect hormone levels
      in amphibians. Using the C-13 labeled atrazine to detect its residue is effective
      and essential. This study presents three steps for the synthesis of [(13) C3
      ]atrazine, which starts from [(13) C]urea, and results in the incorporation of C
      13 atoms at the 1, 3 and 5 positions of the S-triazine ring of atrazine. The
      method prepares the product in an overall yield of 57.6% and chemical purity of
      98.6%, for use as an internal standard.

PMID- 24285377
TI  - An improved synthesis of [11C]MENET via Suzuki coupling with [11C]methyl iodide.
AB  - [(11) C]MENET, a promising norepinephrine transporter imaging agent, was prepared
      by Suzuki cross coupling of 1 mg N-t-Boc pinacolborate precursor with [(11) C]CH3
      I in DMF using palladium complex generated in situ from Pd2 (dba)3 and (o-CH3 C6
      H4 )3 P together with K2 CO3 as the co-catalyst, followed by deprotection with
      trifluoroacetic acid. This improved radiolabeling method provided [(11) C]MENET
      in high radiochemical yield at end of synthesis (EOS, 51 +/- 3%, decay-corrected
      from end of (11) CH3 I synthesis, n = 6), moderate specific activity (1.5-1.9
      Ci/umol at EOS), and high radiochemical (>98%) and chemical purity (>98%) in a
      synthesis time of 60 +/- 5 min from the end of bombardment.

PMID- 24285378
TI  - Synthesis of [15, 16- 3H] beta-funaltrexamine.
AB  - Beta-funaltrexamine is a unique irreversible antagonist for the mu-opiate
      receptor and would be useful as a tritiated radioligand. Starting from high
      specific activity [15, 16-3H] naltrexone, [15, 16-3H] beta-funaltrexamine was
      synthesized and characterized by means of a two-step reductive amination
      acylation process.

PMID- 24285380
TI  - Model-based derivation, analysis and control of unstable microaerobic steady
      states--considering Rhodospirillum rubrum as an example.
AB  - Microaerobic (oxygen-limited) conditions are critical for inducing many important
      microbial processes in industrial or environmental applications. At very low
      oxygen concentrations, however, the process performance often suffers from
      technical limitations. Available dissolved oxygen measurement techniques are not
      sensitive enough and thus control techniques, that can reliable handle these
      conditions, are lacking. Recently, we proposed a microaerobic process control
      strategy, which overcomes these restrictions and allows to assess different
      degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on
      the design of a control strategy for the automation of oxygen-limited continuous
      cultures using the microaerobic formation of photosynthetic membranes (PM) in
      Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the
      considered phenomenon depends on the optimal availability of mixed-carbon
      sources, hence on boundary conditions which make the process performance
      challenging. Empirically assessing these specific microaerobic conditions is
      scarcely practicable as such a process reacts highly sensitive to changes in the
      substrate composition and the oxygen availability in the culture broth.
      Therefore, we propose a model-based process control strategy which allows to
      stabilize steady-states of cultures grown under these conditions. As designing
      the appropriate strategy requires a detailed knowledge of the system behavior, we
      begin by deriving and validating an unstructured process model. This model is
      used to optimize the experimental conditions, and identify properties of the
      system which are critical for process performance. The derived model facilitates
      the good process performance via the proposed optimal control strategy. In
      summary the presented model-based control strategy allows to access and maintain
      microaerobic steady-states of interest and to precisely and efficiently transfer
      the culture from one stable microaerobic steady-state into another. Therefore,
      the presented approach is a valuable tool to study regulatory mechanisms of
      microaerobic phenomena in response to oxygen limitation alone. Biotechnol.
      Bioeng. 2014;111: 734-747. (c) 2013 Wiley Periodicals, Inc. 

PMID- 24285381
TI  - Tunable visible and near-IR photoactivation of light-responsive compounds by
      using fluorophores as light-capturing antennas.
AB  - Although the corrin ring of vitamin B12 is unable to efficiently absorb light
      beyond 550 nm, it is shown that commercially available fluorophores can be used
      as antennas to capture long-wavelength light to promote scission of the Co-C bond
      at wavelengths up to 800 nm. The ability to control the molecular properties of
      bioactive species with long visible and near-IR light has implications for drug
      delivery, nanotechnology, and the spatiotemporal control of cellular behavior.

PMID- 24285382
TI  - National trends in the mental health care of children, adolescents, and adults by
      office-based physicians.
AB  - IMPORTANCE: Despite evidence of the increasing use of psychotropic medications,
      little is known about the broader changes in the delivery of outpatient mental
      health treatment to children, adolescents, and adults. OBJECTIVE: To assess
      national trends and patterns in the mental health care of children, adolescents,
      and adults in office-based medical practice. DESIGN, SETTING, AND PARTICIPANTS:
      Outpatient visits to physicians in office-based practice from the 1995-2010
      National Ambulatory Medical Care Surveys (N = 446 542). Trends (1995-2010) in
      visits with mental health care indicators are first compared between youths (<21
      years) and adults (>=21 years) and then between children (0-13 years) and
      adolescents (14-20 years). Background and clinical characteristics of recent
      visits (2007-2010) resulting in a mental disorder diagnosis are also compared
      among children, adolescents, and adults. MAIN OUTCOMES AND MEASURES: Visits
      resulting in mental disorder diagnoses, prescription of psychotropic medications,
      provision of psychotherapy, or psychiatrist care. RESULTS: Between 1995-1998 and
      2007-2010, visits resulting in mental disorder diagnoses per 100 population
      increased significantly faster for youths (from 7.78 to 15.30 visits) than for
      adults (from 23.23 to 28.48 visits) (interaction: P < .001). Psychiatrist visits
      also increased significantly faster for youths (from 2.86 to 5.71 visits) than
      for adults (from 10.22 to 10.87 visits) (interaction: P < .001). Psychotropic
      medication visits increased at comparable rates for youths (from 8.35 to 17.12
      visits) and adults (from 30.76 to 65.90 visits) (interaction: P = .13). While
      psychotherapy visits increased from 2.25 to 3.17 per 100 population for youths,
      they decreased from 8.37 to 6.36 for adults (interaction: P < .001). In 2007
      2010, 27.4% of child visits, 47.9% of adolescent visits, and 36.6% of adult
      visits resulting in a mental disorder diagnosis were to a psychiatrist.
      CONCLUSIONS AND RELEVANCE: Compared with adult mental health care, the mental
      health care of young people has increased more rapidly and has coincided with
      increased psychotropic medication use. A great majority of mental health care in
      office-based medical practice to children, adolescents, and adults is provided by
      nonpsychiatrist physicians calling for increased consultation and communication
      between specialties.

PMID- 24285383
TI  - The role of phosphoglycerate mutase 1 in tumor aerobic glycolysis and its
      potential therapeutic implications.
AB  - A significant characteristic of cancer cell metabolism is the high level of
      aerobic glycolysis with high glucose consumption and lactate production.
      Phophoglycerate mutase 1 (PGAM1) is an enzyme that catalyzes the interconversion
      of 3-phosphoglycerate and 2-phosphoglycerate during glycolysis. It has been
      reported that this enzyme is commonly upregulated in many human cancers. PGAM1
      plays an important role in coordinating glycolysis and anabolic activity to
      promote cancer cell proliferation. However, the mechanisms under these effects
      are still poorly understood. This review focuses on the most recent advances in
      the structure and functions of PGAM1, and PGAM1's role in glycolysis in cancer
      cells and regulators that modulate PGAM1's effects. Progress in understanding of
      PGAM1 will provide the rationale to support the development of new hypothesis
      driven studies to define PGAM1's potential therapeutic implications for cancer
      treatment. 

PMID- 24285384
TI  - Desorption electrospray ionisation (DESI) for beginners--how to adjust settings
      for tissue imaging.
AB  - RATIONALE: Desorption electrospray ionisation (DESI) is the ambient technique
      used for surface imaging. Despite its simplicity, the proper use of this
      technique is not easy, and usually leads to discouragement, especially in the
      case of biological sample measurements. Here, we present some tips and tricks
      which may be helpful during a complex process of ion source optimisation to
      achieve the desired results. METHODS: Rat liver tissue as an example of a
      biological sample and a surface covered with rhodamine-containing marker were
      measured using a DESI ion source (OMNIspray source, Prosolia, Indianapolis, IN,
      USA) connected to a AmaZon ETD ion trap mass spectrometer (Bruker Daltonics,
      Bremen, Germany). RESULTS: The geometry of the ion source (nebulisation capillary
      angle, its distance to the surface, and to the MS inlet), and other settings like
      nebulising gas pressure, solvent flow and capillary voltage, were changed during
      the optimisation process. The results obtained for different parameters are
      presented. CONCLUSIONS: Differences between the results and the method of
      optimisation for biological and non-biological samples were shown. The influence
      of different parameters on the quality of mass spectra was indicated. Optimal
      parameters for the tissue and non-biological sample analysis were suggested.

PMID- 24285385
TI  - Rapid monitoring of volatile organic compounds: a comparison between gas
      chromatography/mass spectrometry and selected ion flow tube mass spectrometry.
AB  - RATIONALE: The gold standard for monitoring volatile organic compounds (VOCs) is
      gas chromatography/mass spectrometry (GC/MS). However, in many situations, when
      VOC concentrations are at the ppmv level, there are complicating factors for
      GC/MS. Selected ion flow tube mass spectrometry (SIFT-MS) is an emerging
      technique for monitoring VOCs in air. It is simpler to use and provides results
      in real time. METHODS: Three different experiments were used for the comparison.
      First SIFT-MS was applied to monitor the concentrations of 25 VOCs in a mixture
      at concentrations up to 1 ppmv using only a generic database for known kinetic
      data of three reagent ions (H3O(+), NO(+) and O2(+)) with each VOC. In experiment
      2, a side-by-side comparison was made of 17 VOCs at concentrations between 1 ppmv
      and 5 ppbv after small corrections had been made to the SIFT-MS kinetic data. In
      a third experiment, a side-by-side comparison examined two groups of samples
      received for commercial analysis. RESULTS: In experiment 1, 85% of the VOC
      concentrations were within 35% of their stated values without any calibration of
      the SIFT-MS instrument. In experiment 2, the two techniques yielded good
      correspondence between the measured VOC concentrations. In experiment 3, good
      correlation was found for VOCs from three of the samples. However, interferences
      from some product ions gave over-reported values in one sample from the SIFT-MS
      instrument. CONCLUSIONS: These three experiments showed that GC/MS was better
      suited to monitoring samples containing large numbers of VOCs at high
      concentrations. In all other applications, SIFT-MS proved simpler to use, was
      linear with concentration over a much wider concentration range than GC/MS and
      provided faster results.

PMID- 24285386
TI  - Comparison of factors affecting the accuracy of high-precision magnesium isotope
      analysis by multi-collector inductively coupled plasma mass spectrometry.
AB  - RATIONALE: High accuracy is the prerequisite for high-precision isotopic
      analysis. METHODS: Here we evaluate how the presence of matrix elements, and
      mismatch between samples and standards in Mg concentration and acid molarity
      affect the accuracy of stable Mg isotopic analysis on Nu Plasma and IsoProbe
      multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS)
      instruments. RESULTS: Our results show that these factors can lead to large
      (>10/00) deviation in the high-precision analysis of Mg isotopes. The degree and
      direction of these accuracy offsets can vary for different instruments,
      instrumental settings and different laboratories. CONCLUSIONS: Detailed tests and
      tight controls on these effects are thus needed for high-precision high-accuracy
      stable Mg isotopic analysis.

PMID- 24285387
TI  - Tandem mass spectrometry for the study of glyoxal-derived advanced glycation end
      products (AGEs) in peptides.
AB  - RATIONALE: The post-translational modification known as glycation affects the
      physiological properties of peptides and proteins. Glycation is particularly
      important during hyperglycaemia where alpha-dicarbonyl compounds are generated.
      These compounds react with proteins to generate alpha-dicarbonyl-derived
      glycation products, which are correlated with diabetic complications such as
      nephropathy, retinopathy, and neuropathy, among others. One of these alpha
      dicarbonyl compounds is ethanedial, also known as glyoxal. Thereby, glyoxal
      binding to protein/peptides is studied by electron capture dissociation (ECD) and
      collisionally activated dissociation (CAD). METHODS: Acetylated and non
      acetylated undecapeptides containing one lysine and one arginine susceptible of
      glycation were reacted with glyoxal under pseudo-physiological and MeOH/H2O
      (50:50) conditions. Two types of glyoxal-derived AGEs were fragmented by ECD and
      CAD using 12 Tesla Fourier transform ion cyclotron resonance mass spectrometry
      (FTICRMS). RESULTS: Reaction with glyoxal under different reaction conditions
      showed the addition of C2O and C2H2O2, which corresponded to a net increase on
      the peptide mass of 39.9949 Da and 58.0055 Da, respectively. The binding site was
      assigned within an error <1 ppm, using ECD and CAD. The results indicated that
      both types of glyoxal-derived AGEs are formed at the side chain of arginine
      located in position 3. CONCLUSIONS: Types and binding sites of glyoxal-derived
      AGEs were investigated in peptides containing one arginine-one lysine using
      FTICRMS. Two net mass additions to the mass of the peptide were assigned as C2O
      and C2H2O2, which were located at the arginine side chain. In addition, these
      mass additions (C2O and C2H2O2) observed in the peptides were unaffected by
      different reaction conditions.

PMID- 24285388
TI  - Application of de novo sequencing tools to study abiogenic peptide formations by
      tandem mass spectrometry. The case of homo-peptides from glutamic acid
      complicated by substitutions of hydrogen by sodium or potassium atoms.
AB  - RATIONALE: Peptides and proteins are among the most important components of
      living systems. Different attempts have been made to experimentally model the
      formation of peptides from amino acid monomers in investigation of the origin of
      life. Detailed characterization of peptides formed under various conditions in
      such reactions is very important for understanding processes of abiogenic peptide
      formation. METHODS: We used liquid chromatography coupled with tandem mass
      spectrometry (MS/MS) for an accurate study of homo-peptides formed in a model
      reaction: glutamic acid oligomerization catalyzed by 1,1'-carbonyldiimidazole in
      aqueous solution with 1 M of sodium or potassium chloride and without any salts.
      We used de novo sequencing software for peptide identification. In addition we
      propose an approach that uses more spectral information for de novo sequencing
      then standard methods. RESULTS: Peptides up to 9 amino acids long were found in
      the experiments with KCl, while in experiments with NaCl and without salts only
      peptides of up to 7 amino acids were detected. Due to high salt concentrations in
      samples a high number of singly charged peptide ions with up to 4 substitutions
      of hydrogen atoms by sodium or potassium atoms were observed. De novo sequencing
      software provided correct identifications even for peptide ions with
      substitutions. CONCLUSIONS: Multiple substitutions of hydrogen by alkali metal
      atoms in peptide ions strongly change their fragmentation patterns. Proposed
      approach for de novo sequencing was found very effective, even for ions with
      substitutions. So, it may be useful in more complicated cases like sequencing
      abiogenic peptides consisting of different amino acids.

PMID- 24285389
TI  - Reproducibility and accuracy of noble gas measurements on water samples in the
      microlitre range.
AB  - RATIONALE: In order to derive meaningful noble gas temperatures (NGTs) from
      speleothem fluid inclusions, precise and accurate measurements of noble gas
      concentrations on very small water samples are necessary. To optimise these
      measurements and their reliability, an investigation of the reproducibility and
      accuracy of the analytical procedure is essential. METHODS: Water equilibrated
      with air under controlled conditions was filled into copper capillaries to
      produce small (about 1 MUL) air-equilibrated water samples (so-called MUAEWs). As
      speleothem samples, the MUAEWs were opened in a crusher and the released noble
      gases analysed with an electron ionisation sector field mass spectrometer run in
      static mode. For better comparability with speleothem samples, a defined amount
      of air was added to the noble gases derived from one group of MUAEWs. RESULTS:
      The reproducibility of the experimental procedure was found to be better than
      2.2% for all relevant noble gases. Within these uncertainties, the measured noble
      gas concentrations of MUAEWs agree with expectations. The corresponding NGTs
      reproduce within 0.5 degrees C and deviate by less than 1 degrees C from the
      equilibration temperature. In the case of air addition, the air to water ratio
      was determined accurately and, excluding one outlier, the NGTs were determined
      with a reproducibility and accuracy well below 1 degrees C. CONCLUSIONS: The
      results show that the used measurement procedure is generally suitable to reveal
      major climatic temperature changes, for which an overall NGT error of less than 1
      degrees C is desirable, from very small water samples as obtained from speleothem
      fluid inclusions.

PMID- 24285391
TI  - Ultrahigh-performance liquid chromatography/electrospray ionization linear ion
      trap Orbitrap mass spectrometry of antioxidants (amines and phenols) applied in
      lubricant engineering.
AB  - RATIONALE: For the qualification and quantification of antioxidants (aromatic
      amines and sterically hindered phenols), most of them applied as lubricant
      additives, two ultrahigh-performance liquid chromatography (UHPLC) electrospray
      ionization mass spectrometric methods applying the positive and negative ion mode
      have been developed for lubricant design and engineering thus allowing e.g. the
      study of the degradation of lubricants. METHODS: Based on the different chemical
      properties of the two groups of antioxidants, two methods offering a fast
      separation (10 min) without prior derivatization were developed. In order to
      reach these requirements, UHPLC was coupled with an LTQ Orbitrap hybrid tandem
      mass spectrometer with positive and negative ion electrospray ionization for
      simultaneous detection of spectra from UHPLC-high-resolution (HR)-MS (full scan
      mode) and UHPLC-low-resolution linear ion trap MS(2) (LITMS(2)), which we term
      UHPLC/HRMS-LITMS(2). RESULTS: All 20 analytes investigated could be qualified by
      an UHPLC/HRMS-LITMS(2) approach consisting of simultaneous UHPLC/HRMS (elemental
      composition) and UHPLC/LITMS(2) (diagnostic product ions) according to EC
      guidelines. Quantification was based on an UHPLC/LITMS(2) approach due to
      increased sensitivity and selectivity compared to UHPLC/HRMS. Absolute
      quantification was only feasible for seven analytes with well-specified purity of
      references whereas relative quantification was obtainable for another nine
      antioxidants. All of them showed good standard deviation and repeatability.
      CONCLUSIONS: The combined methods allow qualitative and quantitative
      determination of a wide variety of different antioxidants including
      aminic/phenolic compounds applied in lubricant engineering. These data show that
      the developed methods will be versatile tools for further research on
      identification and characterization of the thermo-oxidative degradation products
      of antioxidants in lubricants.

PMID- 24285390
TI  - Correlated matrix-assisted laser desorption/ionization mass spectrometry and
      fluorescent imaging of photocleavable peptide-coded random bead-arrays.
AB  - RATIONALE: Rapidly performing global proteomic screens is an important goal in
      the post-genomic era. Correlated matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) and fluorescent imaging of photocleavable peptide-coded
      random bead-arrays was evaluated as a critical step in a new method for proteomic
      screening that combines many of the advantages of MS with fluorescence-based
      microarrays. METHODS: Small peptide-coded model bead libraries containing up to
      20 different bead species were constructed by attaching peptides to 30-34 um
      diameter glass, agarose or TentaGel(r) beads using photocleavable biotin or a
      custom-designed photocleavable linker. The peptide-coded bead libraries were
      randomly arrayed into custom gold-coated micro-well plates with 45 um diameter
      wells and subjected to fluorescence and MALDI mass spectrometric imaging (MALDI
      MSI). RESULTS: Photocleavable mass-tags from individual beads in these libraries
      were spatially localized as ~65 um spots using MALDI-MSI with high sensitivity
      and mass resolution. Fluorescently tagged beads were identified and correlated
      with their matching photocleavable mass-tags by comparing the fluorescence and
      MALDI-MS images of the same bead-array. Post-translational modification of the
      peptide Kemptide was also detected on individual beads in a photocleavable
      peptide-coded bead-array by MALDI-MSI alone, after exposure of the beads to
      protein kinase A (PKA). CONCLUSIONS: Correlated MALDI-MS and fluorescent imaging
      of photocleavable peptide-coded random bead-arrays can provide a basis for
      performing global proteomic screening.

PMID- 24285392
TI  - Is energy pooling necessary in ultraviolet matrix-assisted laser
      desorption/ionization?
AB  - RATIONALE: Energy pooling has been suggested as the key process for generating
      the primary ions during ultraviolet matrix-assisted laser desorption/ionization
      (UV-MALDI). In previous studies, decreases in fluorescence quantum yields as
      laser fluence increased for 2-aminobenzoic acid, 2,5-dihydroxybenzoic acid (2,5
      DHB), and 3-hydroxypicolinic acid were used as evidence of energy pooling. This
      work extends the research to other matrices and addresses whether energy pooling
      is a universal property in UV-MALDI. METHODS: Energy pooling was investigated in
      a time-resolved fluorescence experiment by using a short laser pulse (355 nm, 20
      ps pulse width) for excitation and a streak camera (1 ps time resolution) for
      fluorescence detection. RESULTS: The excited-state lifetime of 2,5-DHB decreased
      with increases in laser fluence. This suggests that a reaction occurs between two
      excited molecules, and that energy pooling may be one of the possible reactions.
      However, the excited-state lifetime of 2,4,6-trihydroxyacetophenone (THAP) did
      not change with increases in laser fluence. The upper limit of the energy pooling
      rate constant for THAP is estimated to be approximately 100-500 times smaller
      than that of 2,5-DHB. CONCLUSIONS: The small energy pooling rate constant for
      THAP indicates that the potential contribution of the energy pooling mechanism to
      the generation of THAP matrix primary ions should be reconsidered.

PMID- 24285393
TI  - Statistical approach to establish equivalence of unabbreviated mass spectra.
AB  - RATIONALE: In many legal and regulatory applications, mass spectral comparison of
      an unknown or questioned sample to a reference standard or database is used for
      identification; however, no statistical confidence level or error rate is
      determined. Therefore, a simple and rapid method to establish the statistical
      equivalence of mass spectra is needed. METHODS: The standard deviation of the
      abundance at each m/z ratio was determined from replicate measurements or from a
      statistical model. These standard deviations were used in an unequal variance t
      test to compare two spectra at every m/z ratio over the entire scan range. If
      determined to be statistically indistinguishable at every m/z ratio, the random
      match probability (RMP) that the specific mass spectral fragmentation pattern
      occurred by chance was calculated. RESULTS: n-Alkane and alkylbenzene standards
      of varying concentrations were analyzed on the same instrument at different
      ionization voltages. Using the proposed method, replicate spectra were
      successfully associated at the 99.9% confidence level, with RMP values less than
      10(-29). Despite the similarity in fragmentation patterns, spectra were
      distinguished from others in the homologous series. Moreover, the n-alkane
      spectra were appropriately associated to and discriminated from those in a
      standard reference database at the 99.9% confidence level. CONCLUSIONS: A simple
      and rapid method to assign statistical significance to the comparison of mass
      spectra was developed and validated. This method may be useful for legal and
      regulatory applications, such as the identification of controlled substances,
      environmental pollutants, and food and drug contaminants.

PMID- 24285394
TI  - Compound-specific delta13C and delta15N analysis of amino acids: a rapid,
      chloroformate-based method for ecological studies.
AB  - RATIONALE: Compound-specific stable isotope analysis of amino acids has proven
      informative to many ecological systems, but only a handful of analytical methods
      are routinely employed. We evaluated a simple, rapid procedure in which
      biological samples undergo short-duration acid hydrolysis and the resulting amino
      acids are derivatized with methyl chloroformate for gas
      chromatography/combustion/isotope-ratio mass spectrometry (GC/C/IRMS). METHODS:
      Amino acid derivatives were separated on a polar gas chromatography column,
      combusted, and delta(13)C and delta(15)N values were measured. Tests of
      reproducibility and accuracy were conducted for amino acid reference mixtures and
      biological samples. A brief case study of turtles was used to assess whether
      isotopic data were consistent with a priori ecological expectations. RESULTS: The
      methyl chloroformate based reaction successfully converted 15 amino acids from
      acid hydrolysates of biological materials into separable derivatives. The
      delta(13)C and delta(15)N values had high average measurement precision (sigma
      <10/00). Reference materials were measured accurately, with good agreement
      between EA/IRMS and GC/C/IRMS determinations. Analysis of turtle blood samples
      yielded data consistent with their trophic ecology. CONCLUSIONS: This
      derivatization method is a rapid means of determining carbon and nitrogen
      isotopic ratios of amino acids present in the biological materials often sampled
      for ecological studies. While amino acids with charged or polar side chains do
      not have uniformly high recoveries, the average precision of measurements is
      comparable with that of other, more established methods. Batches of samples may
      be prepared from many raw materials in less than a day, representing a
      significant reduction in preparation time over prevailing methods.

PMID- 24285395
TI  - Mass spectrometric study of thermodynamic properties in the Yb2O3-ZrO2 system at
      high temperatures.
AB  - RATIONALE: Materials based on the Yb2O3-ZrO2 system have many industrial
      applications such as high-temperature solid electrolytes, ceramics with special
      properties and most importantly for thermal barrier coatings. As their synthesis
      and use take place at high temperatures, information on the vaporization
      processes, thermodynamic properties and phase equilibria of this system at high
      temperatures is of great importance. METHODS: Measurements were performed by high
      temperature Knudsen effusion mass spectrometry with a MS-1301 mass spectrometer.
      Vaporization was carried out using two tungsten effusion cells containing the
      sample under study and pure Yb2O3. The values of component activities in the
      Yb2O3-ZrO2 system were also calculated using the CALPHAD approach. RESULTS: The
      Yb and O vapor species were identified over the samples studied at 2400 K. Using
      these data the ZrO2 activities, chemical potentials of components and the Gibbs
      energies of the solid solution formation were calculated in this system. The
      thermodynamic values were also obtained as the result of modeling of the Yb2O3
      ZrO2 system based on the CALPHAD approach using the data available on the phase
      diagram of this system and calorimetric measurements only. CONCLUSIONS: The
      thermodynamic functions found in the Yb2O3-ZrO2 system at 2400 K, such as the
      activities of components and the Gibbs energy of formation, displayed negative
      deviation from ideality. Mutual agreement was observed between the experimental
      thermodynamic values and the results of calculations based on the CALPHAD
      approach.

PMID- 24285396
TI  - Signal enhancement of carboxylic acids by inclusion with beta-cyclodextrin in
      negative high-voltage-assisted laser desorption ionization mass spectrometry.
AB  - RATIONALE: It is difficult to directly analyze carboxylic acids in complex
      mixtures by ambient high-voltage-assisted laser desorption ionization mass
      spectrometry (HALDI-MS) in negative ion mode due to the low ionization efficiency
      of carboxylic acids. METHODS: A method for the rapid detection of carboxylic
      acids in negative HALDI-MS has been developed based on their inclusion with beta
      cyclodextrin (beta-CD). RESULTS: The negative HALDI-MS signal-to-noise ratios
      (S/Ns) of aliphatic, aromatic and hetero atom-containing carboxylic acids can all
      be significantly improved by forming 1:1 complexes with beta-CD. These complexes
      are mainly formed by specific inclusion interactions which are verified by their
      collision-induced dissociation behaviors in comparison with that of their
      corresponding maltoheptaose complexes. A HALDI-MS/MS method has been successfully
      developed for the detection of alpha-lipoic acid in complex cosmetics and
      ibuprofen in a viscous drug suspension. CONCLUSIONS: The negative HALDI-MS S/Ns
      of carboxylic acids can be improved up to 30 times via forming non-covalent
      complexes with beta-CD. The developed method shows the advantages of being rapid
      and simple, and is promising for rapid detection of active ingredients in complex
      samples or fast screening of drugs and cosmetics.

PMID- 24285397
TI  - Structural identification of imatinib cyanide adducts by mass spectrometry and
      elucidation of bioactivation pathway.
AB  - RATIONALE: Recent publications have reported that imatinib forms cyanide and
      methoxylamine adducts in vitro but without detail structural identification. The
      current work reports the identification of seven cyanide adducts that elucidate
      the bioactivation pathways and may provide hints for observed clinical adverse
      effects of the drug. METHODS: Imatinib was incubated with human liver microsomal
      proteins in the presence of a NADPH-regeneration system and the trapping agents
      reduced GSH, potassium cyanide and methoxylamine. Samples were analyzed by high
      performance liquid chromatography (HPLC) coupled with a LTQ-Orbitrap data
      collection system. Chemical structures were determined and/or postulated based on
      data-dependent high-resolution tandem mass spectrometric (MS(n)) exact mass
      measurements in both positive and negative scan modes, as well as in combination
      with hydrogen-deuterium exchange (HDX). RESULTS: GSH and methoxylamine conjugates
      were either not detected or were in insufficient quantities for characterization.
      However, seven cyanide conjugates were identified, indicating that the piperazine
      and p-toluidine partial structures in imatinib can become bioactivated and
      subsequently trapped by the nucleophile cyanide ion. The reactive intermediates
      were postulated as imine and imine-carbonyl conjugate (alpha,beta-unsaturated)
      structures on the piperazine ring, and imine-methide on the p-toluidine partial
      structure. CONCLUSIONS: Chemical structures of seven cyanide adducts of imatinib
      have been identified or proposed based on high-resolution MS/MS data. Mechanisms
      for the formation of the conjugates were also proposed. The findings may help to
      understand the mechanism of hepatotoxicity of imatinib in humans.

PMID- 24285398
TI  - Low-mobility-pass filter between atmospheric pressure chemical ionization and
      electrospray ionization sources and a single quadrupole mass spectrometer:
      computational models and measurements.
AB  - RATIONALE: Mixtures of ions produced in sources at atmospheric pressure,
      including chemical ionization (APCI) and electrospray ionization (ESI) can be
      simplified at or near ambient pressure using ion mobility based filters. METHODS:
      A low-mobility-pass filter (LMPF) based on a simple mechanical design and simple
      electronic control was designed, modeled and tested with vapors of 2-hexadecanone
      in an APCI source and with spray of peptide solutions in an ESI source. The LMPF
      geometry was planar and small (4 mm wide * 13 mm long) and electric control was
      through a symmetric waveform in low kHz with amplitude between 0 and 10 V.
      RESULTS: Computational models established idealized performance for transmission
      efficiency of ions of several reduced mobility coefficients over the range of
      amplitudes and were matched by computed values from ion abundances in mass
      spectra. The filter exhibited a broad response function, equivalent to a Bode
      Plot in electronic filters, suggesting that ion filtering could be done in blocks
      ~50 m/z units wide. CONCLUSIONS: The benefit of this concept is that
      discrimination against ions of high mobility is controlled by only a single
      parameter: waveform amplitude at fixed frequency. The effective removal of high
      mobility ions, those of low mass-to-charge, can be beneficial for applications
      with ion-trap-based mass spectrometers to remove excessive levels of solvent or
      matrix ions.

PMID- 24285399
TI  - Electrospray ionization mass spectrometry probing of binding affinity of
      berbamine, a flexible cyclic alkaloid from traditional Chinese medicine, with G
      quadruplex DNA.
AB  - RATIONALE: Classic G-quadruplex binders typically have a large aromatic core and
      interact with G-quadruplexes through pi-pi stacking with the quartets. There are
      rather few reports on natural flexible cyclic molecule from traditional Chinese
      medicine which has high binding affinity with G-quadruplex. METHODS: Electrospray
      ionization mass spectrometry (ESI-MS) experiments were performed to evaluate the
      binding affinities of a natural alkaloid, berbamine, with seven G-quadruplexes.
      Furthermore, we utilized autodock4 analysis to uncover the binding mode of
      berbamine with the G-quadruplex. RESULTS: ESI-MS experiments showed that
      berbamine has the best binding affinity toward the (GGA)8  G-quadruplex compared
      with the other six G-quadruplexes. Autodock4 analysis indicated that berbamine
      interacted with the (GGA)8  G-quadruplex through hydrogen bonding and van der
      Waals forces with a binding site at the lateral groove formed by DG8-DA9-DA15
      DG16. CONCLUSIONS: In this study, we discovered a novel G-quadruplex binder,
      berbamine, which has high binding affinity toward the (GGA)8  G-quadruplex. This
      study provided important clues regarding the probing of small molecule from
      traditional Chinese medicine which can target the G-quadruplex with high
      affinity.

PMID- 24285400
TI  - Involvement of B3GALNT2 overexpression in the cell growth of breast cancer.
AB  - A number of glycosyltransferases have been identified and biologically
      characterized in cancer cells, yet their exact pathophysiological functions are
      largely unknown. Here, we report the critical role of beta1,3-N
      acetylgalactosaminyltransferase II (B3GALNT2), which transfers N
      acetylgalactosamine (GalNAc) in a beta1,3 linkage to N-acetylglucosamine, in the
      growth of breast cancer cells. Comprehensive transcriptomics, quantitative PCR
      and northern blot analyses indicated this molecule to be exclusively upregulated
      in the majority of breast cancers. Knockdown of B3GALNT2 expression by small
      interfering RNA attenuated cell growth and induced apoptosis in breast cancer
      cells. Overexpression of B3GALNT2 in HEK293T cells prompted secretion of the gene
      product into the culture medium, suggesting that B3GALNT2 is potentially a
      secreted protein. Furthermore, we demonstrated that B3GALNT2 is N-glycosylated on
      both Asn-116 and Asn-174 and that this modification is necessary for its
      secretion in breast cancer cells. Our findings suggest that this molecule
      represents a promising candidate for the development of a novel therapeutic
      targeting drug and a potential diagnostic tumor marker for patients with breast
      cancer, especially TNBC.

PMID- 24285401
TI  - Phase transition in dimer liquids.
AB  - We study the phase transition in a system composed of dimers interacting with
      each other via a nearest-neighbor (NN) exchange J and competing interactions
      taken from a truncated dipolar coupling. Each dimer occupies a link between two
      nearest sites of a simple cubic lattice. We suppose that dimers are self-avoiding
      and can have only three orientations, which coincide with the x, y or z
      direction. The interaction J is attractive if the two dimers are parallel to each
      other at the NN distance, zero otherwise. The truncated dipolar interaction is
      characterized by two parameters: its amplitude D and the cutoff distance rc.
      Using the steepest descent method, we determine the ground-state (GS)
      configuration as functions of D and rc. We then use Monte Carlo simulations to
      investigate the nature of the low-temperature phase and to determine
      characteristics of the phase transition from the ordered phase to the disordered
      phase at high temperatures at a given dimer concentration. We show that as the
      temperature increases, dimers remain in the compact state and the transition from
      the low-T compact phase to the disordered phase where dimers occupy the whole
      space is of second order when D is small, but becomes of first order for large
      enough D, for both polarized and nonpolarized dimers. This transition has a
      resemblance to the unfolding polymer transition. The effect of rc is discussed. 

PMID- 24285402
TI  - Synthesis, characterization and antibacterial and antifungal evaluation of some
      para-quinone derivatives.
AB  - Some novel Pyrrolo [2,3-f] Indole-3,7-Dicarbonitrile derivatives (1-5) were
      synthesized using chloranil, malononitrile and anilines. The structures of the
      newly synthesized compounds were characterized by elemental analysis, FT-IR, (1)H
      and (13)C-NMR and mass spectroscopy. These compounds were screened for in vitro
      antibacterial and antifungal activities against some human pathogenic micro
      organisms by employing the disc diffusion technique. Some of the compounds showed
      moderate to good biological activities when compared with standard drugs. 

PMID- 24285403
TI  - Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by
      isoproterenol in male rats.
AB  - Nowadays, cardiovascular diseases and male infertility are two big health
      problems in industrial countries.The aim of the present study was to investigate
      the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired
      spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar
      rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100
      mg/kg) in ISO treated groups. Before ISO administration, pretreatment with
      Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20
      consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant
      concentration as well as testis, epididymis and seminal vesicle weight were
      investigated.Increase in the concentration of MDA and decrease in total
      antioxidant level was observed following ISO administration. Accordingly, the
      sperm viability as well as testis, epididymis and seminal vesicle weights were
      decreased. In the case of sex hormones, the testosterone and LH levels were
      decreased and the concentration of FSH was increased. Pretreatment with L
      carnitine and Coenzyme Q10 significantly decreased the MDA level and increased
      total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and
      Coenzyme Q10 also improved semen parameters and organs weight which were impaired
      by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect
      spermatogenesis in male rats with ISO administration.

PMID- 24285404
TI  - Effects of unprocessed vs. cooked-processed Gastrodia elata on cytochrome P450
      enzymes in rats.
AB  - CONTEXT: Gastrodia elata Blume (GE) has been used as a traditional herb and is
      considered one of the most important medicinal plants in Oriental countries since
      centuries. OBJECTIVE: The purpose of this study was to find out the differences
      between the effects of unprocessed and cooked-processed GE (CGE) on rat
      cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9 and CYP3A4) by using cocktail probe
      drugs in vivo. METHODS: A cocktail solution at a dose of 5 mL/kg, which contained
      phenacetin (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (10 mg/kg), was orally
      administration to rats treated with GE or CGE for 14 days orally. Blood samples
      were collected at a series of time-points and the concentrations of probe drugs
      in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic
      parameters were calculated by the software of DAS 2.0. RESULTS: Both GE and CGE
      did not have significant influences on the pharmacokinetic parameters of
      phenacetin (P>0.05). In addition, CGE decreased the t1/2, Cmax, AUC(0-infinity)
      of tolbutamide (P<0.05) and it increased CL significantly (P<0.01). Furthermore,
      the trend in CGE was similar but far more significant than GE on t1/2, Cmax,
      AUC(0-infinity), and other parameters of midazolam (P<0.05). CONCLUSIONS: In
      conclusion, GE and CGE had no effects on rat CYP1A2. GE did not affect CYP2C9
      activity, but CGE induced the CYP2C9 activity. Moreover, CGE was more potent than
      GE for inhibitory effect on CYP3A4 activity. These results provide useful
      scientific data for the safe clinical application of either extract of GE or in
      combination with other drugs, which should lack the side effects induced by other
      herb-drug interactions.

PMID- 24285405
TI  - Comparative analysis of serum malondialdehyde, antioxidant vitamins and
      immunoglobulin levels in patients suffering from generalized anxiety disorder.
AB  - The relationship between the elevated levels of serum malondialdehyde, depleted
      level of antioxidants (vitamin A, E and C) and altered level of immunoglobulins
      (IgA, IgG and IgM) in several psychiatric disorders has been established by
      various experimental evidences over the past few years. But previously no study
      was carried out to determine these components in patients suffering from
      generalized anxiety disorder (GAD) in Bangladesh. This study was conducted to
      compare the serum concentration of these components in GAD patients and healthy
      volunteers; matched by socioeconomic and sociodemographic parameters. Serum level
      of malondialdehyde and vitamin C were determined by UV spectrophotometric method,
      vitamins A and E were detected by RP-HPLC method whereas immunoglobulin levels
      were determined by turbidimetric method. Data were analyzed by independent t
      test, Pearson's correlation and regression analysis. Significantly lower level of
      vitamin E (p<0.05) and significantly higher level of vitamin C were found in GAD
      patients than the healthy controls, whereas the change of vitamin A was
      insignificant. Serum malondialdehyde content was significantly higher (p<0.05)
      and IgM level was significantly (p<0.05) higher than that of the controls. Change
      in concentrations of IgG and IgA were insignificant (p>0.05). Pearson's
      correlation coefficient suggested that there were some significant positive and
      negative correlations among these tested components. Our study reveals that GAD
      patients have considerably higher level of malondialdehyde, immunoglobulins and
      altered level of antioxidant vitamins. These findings may play a key role in the
      diagnosis and treatment of GAD patients. 

PMID- 24285406
TI  - Risk factors for early revision after total hip arthroplasty.
AB  - OBJECTIVE: Revision total hip arthroplasty (THA) is associated with increased
      cost, morbidity, and technical challenge compared to primary THA. A better
      understanding of the risk factors for early revision is needed to inform
      strategies to optimize patient outcomes. METHODS: A total of 207,256 patients who
      underwent primary THA between 1997-2005 in California and New York were
      identified from statewide databases. Unique patient identifiers were used to
      identify early revision THA (<10 years from index procedure). Patient
      characteristics (demographics, comorbidities, insurance type, and preoperative
      diagnosis), community characteristics (education level, poverty, and population
      density), and hospital characteristics (annual THA volume, bed size, and teaching
      status) were evaluated using multivariable regression to determine risk factors
      for early revision. RESULTS: The probabilities of undergoing early aseptic
      revision and early septic revision were 4% and <1% at 5 years, respectively.
      Women were 29% less likely than men to undergo early septic revision (P < 0.001).
      Patients with Medicaid and Medicare were 91% and 24%, respectively, more likely
      to undergo early septic revision than privately insured patients (P = 0.01 and P
      < 0.001, respectively). Hospitals performing <200 THAs annually had a 34%
      increased risk of early aseptic revision compared to hospitals performing >400
      THAs annually (P < 0.001). CONCLUSION: A number of identifiable factors,
      including younger age, Medicaid, and low hospital volume, increase the risk of
      undergoing early revision THA. Patient-level characteristics distinctly affect
      the risk of revision within 10 years, particularly if due to infection. Our
      findings reinforce the need for continued investigation of the predictors of
      early failure following THA.

PMID- 24285407
TI  - Electron photodetachment dissociation for structural characterization of
      synthetic and bio-polymer anions.
AB  - Tandem mass spectrometry (MS-MS) is a generic term evoking techniques dedicated
      to structural analysis, detection or quantification of molecules based on
      dissociation of a precursor ion into fragments. Searching for the most
      informative fragmentation patterns has led to the development of a vast array of
      activation modes that offer complementary ion reactivity and dissociation
      pathways. Collisional activation of ions using atoms, molecules or surface
      resulting in unimolecular dissociation of activated ions still plays a key role
      in tandem mass spectrometry. The discovery of electron capture dissociation (ECD)
      and then the development of other electron-ion or ion/ion reaction methods,
      constituted a significant breakthrough, especially for structural analysis of
      large biomolecules. Similarly, photon activation opened promising new frontiers
      in ion fragmentation owing to the ability of tightly controlled internal energy
      deposition and easy implementation on commercial instruments. Ion activation by
      photons includes slow heating methods such as infrared multiple photon
      dissociation (IRMPD) and black-body infrared radiative dissociation (BIRD) and
      higher energy methods like ultra-violet photodissociation (UVPD) and electron
      photo detachment dissociation (EPD). EPD occurs after UV irradiation of multiply
      negatively charged ions resulting in the formation of oxidized radical anions.
      The present paper reviews the hypothesis regarding the mechanisms of electron
      photo-detachment, radical formation and direct or activated dissociation pathways
      that support the observation of odd and even electron product ions. Finally, the
      value of EPD as a complementary structural analysis tool is illustrated through
      selected examples of synthetic polymers, oligonucleotides, polypeptides, lipids,
      and polysaccharides.

PMID- 24285408
TI  - Highly efficient top-illuminated flexible polymer solar cells with a
      nanopatterned 3D microresonant cavity.
AB  - Top-illuminated flexible polymer solar cells with 3D micoresonant cavity provide
      not only powerful light-trapping but also electrical enhancement, resulting in
      significant enhancement of power efficiency (26.4%). Capping layer (CL) enhanced
      the transmittance of the transparent electrodes, increasing electric field
      intensity in the photoactive layer by forming microresonant cavity, and the nano
      pattern on the rear electrodes caused significant enhancement to the Jsc by
      improving light absorption and charge collection. 

PMID- 24285409
TI  - Beware imposters: MA-1, a novel MALT lymphoma cell line, is misidentified and
      corresponds to Pfeiffer, a diffuse large B-cell lymphoma cell line-A reply:
      despite the same 8-code STR, MA-1 and Pfeiffer are cytogenetically diverse.

PMID- 24285410
TI  - Fully automated radiosynthesis of [1-(2-[18 F]fluoroethyl),1H[1,2,3]triazole 4
      ethylene] triphenylphosphonium bromide as a potential positron emission
      tomography tracer for imaging apoptosis.
AB  - A novel phosphonium salt bearing a fluorine-18 labelled triazole has been
      designed as a potential imaging agent for apoptosis. The radiosynthesis of [1-(2
      [(18)F]fluoroethyl),1H[1,2,3]triazole 4-ethylene] triphenylphosphonium bromide
      ([(18)F]MitoPhos_01) has been carried out on a fully automated system in a two
      step reaction. Radiolabelling an ethyl azide and then carrying out a copper
      mediated 1,3-cycloaddition reaction has allowed for total synthesis time to be
      slightly more than 1 h from aqueous [(18)F]fluoride. After purification by HPLC,
      the average radiochemical yield was determined to be 9% (not decay corrected);
      the specific activity was on average 70 GBq/umol at the end of synthesis, and the
      radiochemical purity was >99%.

PMID- 24285411
TI  - Synthesis of selectively labeled histidine and its methylderivatives with
      deuterium, tritium, and carbon-14.
AB  - Isotopologues of l-histidine and its N-methylderivatives labeled with deuterium
      and tritium at the 5-position in the imidazole ring were obtained using the
      isotope exchange method. The deuterium-labeled isotopologues [5-(2)H]-l
      histidine, [5-(2)H]-N(tau) -methyl-l-histidine, [5-(2)H]-N(pi) -methyl-l
      histidine, and [2,5-(2)H(2)]-l-histidine were synthesized by isotope exchange
      method carried out in a fully deuterated medium with. The same reaction
      conditions were applied to synthesize [5-(3)H]-N(tau) -methyl-l-histidine, [5
      (3)H]-N(pi) -methyl-l-histidine, and [5-(3)H]-l-histidine with specific activity
      of 2.0, 5.0, and 2.6 MBq/mmol, respectively. The N(pi) -[methyl-(14)C]-histamine
      was obtained with specific activity of 0.23 MBq/mmol in a one-step reaction by
      the direct methylation of histamine by [(14)C]iodomethane.

PMID- 24285412
TI  - Carbon-14 radiosynthesis of the benzofuran derivative and beta-amyloid plaque
      neuroimaging positron emission tomography radioligand AZD4694.
AB  - In support of a metabolite study, the beta-amyloid plaque neuroimaging positron
      emission tomography radioligand AZD4694 was labeled with carbon-14 in 10
      radiosynthetic steps starting from radiolabeled carbon dioxide. [(14)C]AZD4694
      was labeled in the benzofuran heterocycle with a specific activity of 2.1
      GBq/mmol and with a radiochemical purity of >99%. The described synthesis
      constitutes a general method to carbon-14-labeled substituted benzofurans.

PMID- 24285413
TI  - A facile synthesis of deuterium labeled 2,2-dimethyl-[2H6]-succinic acid and its
      anhydride.
AB  - Deuterium labeled 2,2-dimethyl-[(2)H(6)]-succinic anhydride by a sequence of
      reactions involving Knoevenagel condensation of [(2)H(6)]-acetone with ethyl
      cyanoacetate in the presence of piperidine, Michael addition of cyanide, HCl
      hydrolysis, simultaneous decarboxylation, and subsequent dehydration using acetic
      anhydride in an overall yield of 34.23% based on [(2)H(6)]-acetone utilized in
      the reaction is reported. The title compounds were characterized and confirmed
      spectroscopically by Fourier transform infrared, (1) H-NMR, and Mass. The
      chemical purity as determined by HPLC was 99%. To the best of our knowledge, the
      synthesis of these specifically deuterium labeled compounds has not been reported
      so far.

PMID- 24285414
TI  - Use of LC-MS for the quality control of radiopharmaceuticals: example of
      [(18)F]ML10.
AB  - [(18)F]ML10 is a promising novel low molecular weight positron emission
      tomography probe for apoptosis. As part of the quality control to support
      clinical studies for cancer therapy monitoring in the GSK Clinical Imaging
      Centre, a simple and sensitive liquid chromatography mass spectrometry method has
      been developed and validated for the quantification of total ML10 and impurity
      content in the final product. Chromatographic separation of ML10 and its
      radiolabelling precursor and impurities was achieved. Mass curves were
      constructed from a concentration range of ML10 and known impurities and were
      linear. Quantification was achieved by comparison of the area under the curve for
      ML10 content (m/z = 205) and the mass curve. The method was validated over a
      concentration range of 0.1-1 ug/ml.

PMID- 24285415
TI  - Synthesis of ximelagatran, melagatran, hydroxymelagatran, and ethylmelagatran in
      H-3 labeled form.
AB  - In support of a study designed to better understand the liver toxicity of
      ximelagatran, ximelagatran, and melagatran, hydroxymelagatran and ethylmelagatran
      were prepared in tritium labeled form. Incorporation of tritium was achieved by
      hydrogen isotope exchange using Crabtree's catalyst and later with N-heterocyclic
      containing Ir catalyst. The tritiated product was then converted into the four
      target compounds to afford them in high purity and specific activity. 

PMID- 24285418
TI  - Direct alpha-vinylidenation of aldehydes and subsequent cascade: gold and amine
      catalysts work synergistically.
AB  - Carbonyl-substituted allenes are highly important synthetic intermediates for a
      number of heterocycles and strained-ring systems. However, chemistry of allenyl
      aldehydes has not been explored as extensively as their ketone, ester, or amide
      analogues because of a lack of general synthetic methods. Described herein is the
      first direct alpha-vinylidenation of aldehydes and an alpha-vinylidenation/gamma
      functionalization cascade to access tri- and tetrasubstituted allenyl aldehydes
      using a combination of a gold catalyst and an secondary amine. The reactive
      enamine intermediate of an aldehyde reacts with the gold-activated hypervalent
      silylethynyl benziodoxolone to selectively generate the corresponding
      trisubstituted allenyl aldehyde. The allenyl aldehyde can further react with
      another equivalent of the alkynylation reagent or other electrophiles to afford
      tetrasubstituted allenes bearing an aldehyde group, an acetylene, and a halogen
      functionality. This method enables rapid access to polysubstituted furans from
      aldehydes. 

PMID- 24285419
TI  - Insights into the mechanisms of sclerostin action in regulating bone mass
      accrual.

PMID- 24285420
TI  - A mechanistic study on the metastasis inducing function of FUS-CHOP fusion
      protein in liposarcoma.
AB  - The FUS-CHOP fusion protein has been found to be instrumental for specific
      oncogenic processes in liposarcoma, but its ability to induce metastasis and the
      underlying mechanisms by which this can be achieved remain unknown. To dissect
      its functional role in this context, we stably overexpressed this protein in
      SW872 liposarcoma and HT1080 fibrosarcoma cell lines, and were able to
      demonstrate that forced expression of FUS-CHOP significantly increases migration
      and invasion, as well as enhances lung and liver metastasis in the in vivo
      chicken chorioallantoic membrane (CAM) model, that is proliferation independent.
      Additionally, FUS-CHOP enhances the expression of matrix-metalloproteinases -2
      and -9, and transactivates their promoters in vitro. Mutational analysis showed
      that C/EBP-beta- (-769/-755), NF-kappaB (-525/-516) and CREB/AP-1 (-218/-207)
      sites were important for MMP-2 and NF-kappaB (-604/-598), AP-1 (-539/-532) and AP
      1 (-81/-72) for MMP-9 transactivation. Moreover, a direct in vivo interaction of
      FUS-CHOP was observed in case of the MMP-2 promoter within region (-769/-207).
      siRNA data revealed that MMP-2 expression is essential in the FUS-CHOP induced
      metastatic phenotype. MMP-2-mRNA and protein expression correlated significantly
      with FUS-CHOP positivity in 46 resected patient liposarcoma tissues. We have for
      the first time provided substantial evidence for the FUS-CHOP oncoprotein as an
      inducer of metastasis that is due to the transcriptional induction of specific
      tumor-associated proteases. Insights gained from this study not only support a
      deeper understanding of the mechanistic properties of FUS-CHOP, but also open up
      new avenues for targeted therapy. 

PMID- 24285421
TI  - Improving limited-view photoacoustic tomography with an acoustic reflector.
AB  - The versatility and real-time imaging capability of commercial linear array
      transducers make them widely used in clinical ultrasound and photoacoustic
      imaging. However, they often suffer from limited detection view. For instance,
      acoustic waves traveling at a grazing angle to the transducer surface are
      difficult to detect. In this letter, we propose a simple and easy approach to
      ameliorate this problem by using a 45-deg acoustic reflector. The reflector forms
      a virtual array that is perpendicular to the physical array, thereby doubling the
      detection coverage. The improvement in image quality in photoacoustic tomography
      was demonstrated through a hair phantom, a leaf skeleton phantom, and an ex vivo
      mouse ear experiment.

PMID- 24285422
TI  - In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell
      carcinoma.
AB  - Aldehyde dehydrogenase isoform 1 (ALDH1) is a useful marker of cancer-initiating
      cells (CICs) in various organs. In this study, we investigated whether
      alterations in ALDH1 immunostaining and enzymatic activity in tumor cell
      populations predicted clinicopathological factors of prognostic importance for
      cancer progression and contributed to the characteristics of CICs in cisplatin
      treated oral squamous cell cancer (OSCC) cells. We evaluated the association
      between the proportion of ALDH1-positive tumor cells and the clinicopathological
      features in 90 patients with OSCC. We also examined ALDH1 enzymatic activity,
      ABCG2 expression, invasive capacity and the ability to self-renew in OSCC cells
      treated with or without cisplatin. The clinicopathological results showed that
      elevated ALDH1 expression correlated with local recurrence. In in vitro
      experiments, the percentage of cells exhibiting ALDH1 enzymatic activity
      significantly increased among cisplatin-surviving cells (CiSCs) according to flow
      cytometry. Furthermore, CiSCs demonstrated upregulated expression of ABCG2, their
      invasive capacity increased, and their ability to generate cancer spheres was
      enhanced. An increased population of cells exhibiting ALDH1 immunostaining is a
      predictive marker of local recurrence. ALDH1 expression and activity contributes
      to the characteristics of CICs in OSCC.

PMID- 24285423
TI  - Timeliness of second opinion appointed doctors' assessments of treatment plans
      for patients detained in medium security hospitals in London, UK.
AB  - BACKGROUND: Mental health legislation in England & Wales requires assessment by a
      second opinion appointed doctor (SOAD) to safeguard the rights of patients
      detained in a hospital under this law if they are either refusing certain
      treatments or are deemed incapable of consenting to them. AIMS: Our aim was to
      evaluate timeliness of SOAD assessments. METHOD: Data were collected from the
      Mental Health Act administrator on all SOAD requests in 1 year for all in
      patients in two English medium security hospital units. RESULTS: One hundred and
      six patients required a SOAD assessment during the 1-year period examined, of a
      combined resident total of 295, as did a further 14 patients who had been
      discharged from hospital and were subject to a community treatment order. About
      half of the inpatients were seen by a SOAD within 30 days and a further quarter
      within 60 days, but the remaining quarter waited up to 150 days or more.
      DISCUSSION AND IMPLICATIONS: These results suggest that in these trusts, unlikely
      to be atypical, neither patients nor clinicians are being adequately protected by
      legal safeguards on decisions to treat with medication (or electroconvulsive
      therapy) in the event of impaired competence for decisions about mental health
      treatments. There should be clear standards for the appropriate length of time
      from referral to assessment by an independent doctor (SOAD). Compliance with
      standards should be transparent, so anonymised data on the matter should be
      routinely collected and stored by health trust Mental Health Act offices. Data
      should be monitored at agreed intervals by an independent body.

PMID- 24285424
TI  - X-ray absorption spectroscopy of GeO2 glass to 64 GPa.
AB  - The structural behavior of GeO2 glass has been investigated up to 64 GPa using
      results from x-ray absorption spectroscopy in a diamond anvil cell combined with
      previously reported density measurements. The difference between the nearest Ge-O
      distances of glassy and rutile-type GeO2 disappears at the Ge-O distance maximum
      at 20 GPa, indicating completion of the tetrahedral-octahedral transition in GeO2
      glass. The mean-square displacement sigma(2) of the Ge-O distance in the first Ge
      O shell increases progressively to a maximum at 10 GPa, followed by a substantial
      reduction at higher pressures. The octahedral glass is, as expected, less dense
      and has a higher compressibility than the corresponding crystalline phase, but
      the differences in Ge-O distance and density between the glass and the crystals
      are gradually eliminated over the 20-40 GPa pressure range. Above 40 GPa, GeO2
      forms a dense octahedral glass with a compressibility similar to that of the
      corresponding crystalline phase (alpha-PbO2 type). The EXAFS and XANES spectra
      show evidence for subtle changes in the dense glass continuing to occur at these
      high pressures. The Ge-O bond distance shows little change between 45-64 GPa, and
      this may reflect a balance between bond shortening and a gradual coordination
      number increase with compression. The density of the glass is similar to that of
      the alpha-PbO2-type phase, but the Ge-O distance is longer and is close to that
      in the higher-coordination pyrite-type phase which is stable above ~60 GPa. The
      density data provide evidence for a possible discontinuity and change in
      compressibility at 40-45 GPa, but there are no major changes in the corresponding
      EXAFS spectra. A pyrite-type local structural model for the glass can provide a
      reasonable fitting to the XAFS spectra at 64 GPa. 

PMID- 24285425
TI  - First ray kinematics in women with rheumatoid arthritis and bunion deformity: a
      gait simulation imaging study.
AB  - OBJECTIVE: The first ray plays a role in the development of bunion foot
      deformity, but for unknown reasons. This prospective, cross-sectional study
      investigated first ray kinematics in women with rheumatoid arthritis (RA) and
      bunion. METHODS: Nine participants having RA-bunion were analyzed in comparison
      to a control group (n = 10). Data were acquired using a magnetic resonance
      scanner. Conditions were standardized to simulate gait midstance, heel off, and
      terminal stance. Foot posture (hallux angle, intermetatarsal angle, arch angle,
      and calcaneus angle) and relative first ray position angles/helical axis
      parameters registered across gait conditions were measured. An analysis of
      variance model compared data between groups and across conditions, and
      correlation assessed the relationship between selected variables. RESULTS:
      Eversion of the calcaneus averaged 9 degrees , and adduction of the first ray was
      increased (F = 6.29, P = 0.02) by >=4.6 degrees  across conditions in the RA
      bunion group. There was an interaction (F = 7.73, P = 0.01) for the first ray
      axis. Followup comparisons identified increased inclination of the first ray axis
      over middle stance compared to late stance in the group with RA and bunion. There
      was moderate correlation (r = -0.42) between the calcaneus angle of eversion and
      inclination of the first ray axis. CONCLUSION: Optimal treatment for bunion has
      not been defined. This research identified calcaneus eversion and first ray
      adduction, as well as inclination of the first ray axis as risk factors of
      bunion. This result may inform the evaluation and treatment of bunion in women
      with RA.

PMID- 24285426
TI  - MALDI of synthetic polymers with labile end-groups.
AB  - Mass spectrometry is increasingly used in the field of synthetic polymers as a
      fast and accurate technique for end-group analysis. More particularly, matrix
      assisted laser desorption/ionization (MALDI) has gained much popularity because
      it allows quite simple mass spectra to be obtained, displaying a single
      distribution for each polymeric species present in the sample, in contrast to
      electrospray ionization (ESI) which readily promotes multiple charging for most
      polymers. A soft ionization process, ensuring the integrity of the species upon
      transfer into gas phase ions, is however mandatory for polymer end-group analysis
      since information about the chain terminations mainly rely on the m/z values
      measured for polymer adducts. As compared to ESI, MALDI is sometimes suspected to
      be a quite "hard" ionization technique, leading to spontaneous dissociation of
      ionized species either in the source or during their flight time. This issue is
      of particular concern for polymers carrying so-called fragile end-groups arising
      from their mode of synthesis. In particular, controlled radical polymerization
      (CRP) processes, one of the most important advances in the field of polymer
      science during the last 20 years, allow the production of polymers with well
      defined molecular distribution and low polydispersities, but they are all based
      on the low dissociation energy of the chemical bond between the last monomer and
      the terminating group. As a result, if macromolecules are activated while being
      ionized, this end-group is prone to fragmentation and ions measured in the mass
      spectra do no longer reflect the original chain composition. However, different
      results are reported in the literature about the ability of MALDI to generate
      intact ions from CRP synthetic polymers. This article reviews MALDI MS data
      reported for synthetic polymers produced by atom transfer radical polymerization
      (ATRP), reversible addition-fragmentation transfer polymerization (RAFT), and
      nitroxide-mediated polymerization (NMP), the three most studied CRP techniques.
      The general principle of each polymerization process, which defines the structure
      of the end-groups in both targeted macromolecules and species arising from
      eventual side-reactions, is first briefly presented. An overview of MALDI data
      reported for samples obtained upon polymerization of different monomers are then
      commented for each polymerization techniques with regards to the success of the
      ionization method to generate intact cationic adducts and its propensity to
      distinguish in-source fragments from polymerization side-products.

PMID- 24285427
TI  - Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK
      trial): a rationale and study protocol.
AB  - BACKGROUND: Patients on haemodialysis (HD) exhibit increased cardiovascular
      mortality associated with accelerated vascular calcification (VC). VC is
      influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in
      the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and
      supplementation with vitamin K reduces inactive MGP levels in these patients. The
      VitaVasK trial analyses whether vitamin K1 supplementation affects the
      progression of coronary and aortic calcification in HD patients. METHODS:
      VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT
      No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm
      design. After baseline multi-slice computed tomography (MSCT) of the heart and
      thoracic aorta, patients with a coronary calcification volume score of at least
      100 will be randomized to continue on standard care or to receive additional
      supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration
      will be 18 months, and MSCT scans will be repeated after 12 and 18 months.
      Primary end points are the progression of thoracic aortic and coronary artery
      calcification (calculated as absolute changes in the volume scores at the 18
      month MSCT versus the baseline MSCT). Secondary end points comprise changes in
      Agatston score, mitral and aortic valve calcification as well as major adverse
      cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to
      record MACE and all-cause mortality in the follow-up period at 3 and 5 years
      after treatment initiation. This trial may lead to the identification of an
      inexpensive and safe treatment or prophylaxis of VC in HD patients.

PMID- 24285429
TI  - Transplantation-steroid-impaired glucose metabolism: a hope for improvement?

PMID- 24285428
TI  - Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding
      study.
AB  - BACKGROUND: Haemodialysis patients suffer from accelerated vascular
      calcification. The vitamin K-dependent matrix Gla protein (MGP) is one of the
      most powerful inhibitors of vascular calcification. Haemodialysis patients have
      high levels of the inactive form of MGP (desphosphorylated-uncarboxylated-MGP, dp
      uc-MGP) and may benefit from pharmacological doses of vitamin K2 (menaquinone) to
      improve the calcification inhibitory activity of MGP. METHODS: To determine the
      optimal dose of menaquinone-7 (MK-7) for MGP activation, 200 chronic
      haemodialysis patients were recruited to randomly receive 360, 720 or 1080 ug of
      MK-7 thrice weekly for 8 weeks. Dp-uc-MGP was measured at baseline and after 8
      weeks. Dietary intake of vitamin K1 (phylloquinone) and menaquinone was estimated
      based on a detailed questionnaire. RESULTS: At baseline, dp-uc-MGP was not
      associated with phylloquinone intake (P = 0.92), but correlated inversely with
      menaquinone intake (P = 0.023). MK-7 supplementation dose dependently reduced dp
      uc-MGP. The levels decreased by 17, 33 and 46% in the respective groups. Drop
      outs were mainly due to gastrointestinal side-effects related to the unpleasant
      smell of the tablets. CONCLUSIONS: Chronic haemodialysis patients have high
      levels of inactive MGP, possibly related to a low dietary vitamin K intake.
      Pharmacological doses of MK-7 dose-dependently reduce dp-uc-MGP. Menaquinone
      supplementation may be a novel approach to prevent vascular calcifications in
      chronic haemodialysis patients.

PMID- 24285430
TI  - Gold carbenoids: lessons learnt from a transmetalation approach.
AB  - Carbophilic catalysts that are based on Au(I) allow a host of different
      nucleophiles to be added across various pi systems. Although many of these
      reactions are thought to proceed via gold carbenoids, the challenge to observe
      and characterize these putative intermediates has basically been unmet. The
      current mechanistic interpretation therefore largely relies on indirect evidence
      and computational data, some of which are subject to debate. In an attempt to
      fill this gap, we pursued a potential route to gold carbenoids by formal
      transmetalation of chromium or tungsten Fischer carbene complexes with [LAu](+).
      Whereas this transformation proceeds with exceptional ease as long as a
      stabilizing heteroelement is present on the carbene center, it stops half-way in
      its absence. Rather unusual bimetallic arrays are formed, which allow the charge
      density to delocalize over several positions. The obvious difficulty of releasing
      an "unstabilized" gold carbenoid has potential mechanistic implications for the
      understanding of pi-acid catalysis in general.

PMID- 24285431
TI  - Business not as usual.

PMID- 24285432
TI  - The eye pupil adjusts to imaginary light.
AB  - If a mental image is a rerepresentation of a perception, then properties such as
      luminance or brightness should also be conjured up in the image. We monitored
      pupil diameters with an infrared eye tracker while participants first saw and
      then generated mental images of shapes that varied in luminance or complexity,
      while looking at an empty gray background. Participants also imagined familiar
      scenarios (e.g., a "sunny sky" or a "dark room") while looking at the same
      neutral screen. In all experiments, participants' eye pupils dilated or
      constricted, respectively, in response to dark and bright imagined objects and
      scenarios. Shape complexity increased mental effort and pupillary sizes
      independently of shapes' luminance. Because the participants were unable to
      voluntarily constrict their eyes' pupils, the observed pupillary adjustments to
      imaginary light present a strong case for accounts of mental imagery as a process
      based on brain states similar to those that arise during perception.

PMID- 24285433
TI  - Unconscious processing of an abstract concept.

PMID- 24285435
TI  - Synthesis of [13C6]primaquine.
AB  - In support of a program to identify toxic metabolites of the antimalarial,
      primaquine, its [(13)C6] analog was prepared from [(13)C6] anisole in seven
      steps.

PMID- 24285434
TI  - Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid
      tumors--molecular characterization shows genetic overlap with endometrial stromal
      sarcoma.
AB  - PHF1 gene rearrangements have been recently described in around 50% of ossifying
      fibromyxoid tumors (OFMT) including benign and malignant cases, with a small
      subset showing EP400-PHF1 fusions. In the remaining cases no alternative gene
      fusions have been identified. PHF1-negative OFMT, especially if lacking S100
      protein staining or peripheral ossification, are difficult to diagnose and
      distinguish from other soft tissue mimics. In seeking more comprehensive
      molecular characterization, we investigated a large cohort of 39 OFMT of various
      anatomic sites, immunoprofiles and grades of malignancy. Tumors were screened for
      PHF1 and EP400 rearrangements by FISH. RNA sequencing was performed in two index
      cases (OFMT1, OFMT3), negative for EP400-PHF1 fusions, followed by FusionSeq data
      analysis, a modular computational tool developed to discover gene fusions from
      paired-end RNA-seq data. Two novel fusions were identified ZC3H7B-BCOR in OFMT1
      and MEAF6-PHF1 in OFMT3. After being validated by FISH and RT-PCR, these
      abnormalities were screened on the remaining cases. With these additional gene
      fusions, 33/39 (85%) of OFMTs demonstrated recurrent gene rearrangements, which
      can be used as molecular markers in challenging cases. The most common
      abnormality is PHF1 gene rearrangement (80%), being present in benign, atypical
      and malignant lesions, with fusion to EP400 in 44% of cases. ZC3H7B-BCOR and
      MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant
      OFMT. As similar gene fusions were reported in endometrial stromal sarcomas, we
      screened for potential gene abnormalities in JAZF1 and EPC1 by FISH and found two
      additional cases with EPC1-PHF1 fusions.

PMID- 24285436
TI  - Preparation of deuterium-labeled biotransformation products of 2,4,6
      trinitrotoluene.
AB  - Methods for the preparation of deuterium-labeled analogs to six prominent
      biotransformation products of the explosive 2,4,6-trinitrotoluene were developed.
      These are useful as reference standards for stable isotope dilution techniques
      and for solid state (2)H NMR spectroscopic studies. Although syntheses for most
      of the target compounds in protiated form had been reported in the past, most of
      those were found to be poorly suited for the preparation of the deuterated
      materials. Selective reduction of [(2)H5]trinitrotoluene furnished [(2)H5]-4,6
      dinitro-2-hydroxylaminotoluene, [(2)H5]-2,6-dinitro-4-hydroxylaminotoluene,
      [(2)H5]-2-amino-4,6-dinitrotoluene, and [(2)H5]-4-amino-2,6-dinitrotoluene. The
      syntheses of [(2)H10]-2,2'-azo-4,4',6,6'-tetranitrotoluene and [(2)H10]-4,4'-azo
      2,2',6,6'-tetranitrotoluene were accomplished by selective oxidation of [(2)H5]-2
      amino-4,6-dinitrotoluene and [(2)H5]-4-amino-2,6-dinitrotoluene, respectively.

PMID- 24285437
TI  - Straightforward preparation of labeled potassium cyanate by ozonation and
      application to the synthesis of [13C] or [14C]ureidocarboxylic acids.
AB  - The development of new efficient syntheses of labeled reagents is a great
      challenge. Avoidance of overcomplicated procedures, availability and cost of
      starting materials are important considerations in choosing the synthetic route.
      In this report, we describe a facile and rapid preparation of labeled cyanate by
      ozonation of cyanide, a basic precursor. The crude cyanate was used without
      purification for the synthesis of various [(13)C] or [(14)C]ureidocarboxylic
      acids (20-68% yield from potassium cyanide). According to these results, cyanide
      ozonation may prove to be a promising alternative to traditional preparations of
      labeled cyanate.

PMID- 24285439
TI  - Two-step radiosynthesis of 18)F]FE-beta-CIT and [18F]PR04.MZ.
AB  - The cocaine-derived dopamine reuptake inhibitors FE-beta-CIT (8-(2-fluoroethyl)-3
      (4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester) (1) and
      PR04.MZ(8-(4-fluorobut-2-ynyl)-3-p-tolyl-8-azabicyclo[3.2.1]octane-2-carboxylic
      acid methyl ester) (2) were labelled with (18)F-fluorine using a two-step route.
      2-[(18)F]Fluoroethyltosylate and 4-[(18)F]fluorobut-2-yne-1-yl tosylate were used
      as labelling reagents, respectively. Radiochemically pure (>98%) [(18)F]FE-beta
      CIT and [(18)F]PRD04.MZ (32-86 GBq/umol) were obtained after a synthesis time of
      100 min in about 25% non-decay-corrected overall yield.

PMID- 24285438
TI  - An improved synthesis of 1'-[18F]fluoroethyl-beta-D-lactose ([18F]-FEL) for
      positron emission tomography imaging of pancreatic cancer.
AB  - INTRODUCTION: Earlier, we reported syntheses of ethyl-beta-D-galactopyranosyl
      (1,4')-2'-deoxy-2'-[(18)F]fluoro-beta-D-glucopyranoside (Et-[(18)F]FDL) and 1'
      [(18)F]fluoroethyl-beta-D-lactose ([(18)F]-FEL) for positron emission tomography
      (PET) of pancreatic carcinoma. Et-[(18)F]FDL requires a precursor, which involves
      11 steps to synthesize and produces overall low yields. Synthesis of precursors
      for [(18)F]-FEL requires four steps, but those precursors produced low
      radiochemical yields. Here, we report new precursors and an improved synthesis of
      [(18)F]-FEL. METHOD: Two precursors, 1'-(methanesulfonyl)ethyl-2',3',6',2,3,4,6
      hepta-O-acetyl-beta-D-lactose 2a and 1'-(p-nitrophenyl-sulfonyl)ethyl
      2',3',6',2,3,4,6-hepta-O-acetyl-beta-D-lactose 2b, were synthesized from lactose
      in four steps. Radiofluorination reactions were performed using K(18)F/kryptofix
      and the crude product [(18)F]-3 was purified by HPLC. Basic hydrolysis of [(18)F]
      3 produced 1'-[(18)F]fluoroethyl-beta-D-lactose [(18)F]-4, which was neutralized,
      diluted with saline, filtered on a 0.22-um filter, and analyzed by radio-TLC.
      RESULTS: The average radiochemical yields of [(18)F]-4 (d. c.) from 2a and 2b
      were 21% (n = 6) and 65% (n = 6), respectively, with >99% radiochemical purity
      and specific activity of 55.5 GBq/umol. Synthesis time was 90-95 min from the end
      of bombardment. CONCLUSION: An improved synthesis of [(18)F]FEL has been achieved
      in high yields, with high purity and specific activity. Precursor 2b with this
      method should be applicable for high yield automated production in a commercial
      synthesis module for clinical application.

PMID- 24285440
TI  - Automated synthesis and purification of [18F]fluoro-[di-deutero]methyl tosylate.
AB  - Automated synthetic procedures of [(18)F]fluoro-[di-deutero]methyl tosylate on a
      GE TRACERlab FX F-N module and a non-commercial synthesis module have been
      developed. The syntheses included azeotropic drying of the [(18)F]fluoride,
      nucleophilic (18)F-fluorination of bis(tosyloxy)-[di-deutero]methane, HPLC
      purification and subsequent formulation of the synthesized [(18)F]fluoro-[di
      deutero]methyl tosylate (d2-[(18)F]FMT) in organic solvents. Automation shortened
      the total synthesis time to 50 min, resulting in an average radiochemical yield
      of about 50% and high radiochemical purity (>98%). The possible application of
      this procedure to commercially available synthesis modules might be of
      significance for the production of deuterated (18)F-fluoromethylated imaging
      probes in the future.

PMID- 24285442
TI  - The quest for photocatalytic systems with broadband solar absorption.
AB  - Composite heteronanostructures hold promise for high photocatalytic efficiency
      for water splitting and the degradation of organic pollutants. However, their
      photocatalytic activity under broadband excitation has been challenging, until
      now. 

PMID- 24285443
TI  - Open access under scrutiny.

PMID- 24285444
TI  - Lung hernia - a review.
AB  - Lung hernia is a protrusion of lung tissue through one of its bounding
      structures. This uncommon condition develops most commonly as a result of trauma
      or after thoracic operations. Other lung hernias, particularly supraclavicular,
      are congenital. Diagnosis is usually clinical, but must be confirmed by
      roentgenography or computed tomography. Presence of incarceration or other
      symptoms makes operation obligatory. Incarcerated tissue should be released
      promptly, but may have to be resected. For closure of a hernia defect the use of
      autologous tissues is recommended. When these are not available, synthetic
      materials are acceptable. Some hernias are asymptomatic and no treatment is
      necessary. 

PMID- 24285445
TI  - Tannic Acid influence on lead and cadmium accumulation in the hearts and lungs of
      rats.
AB  - BACKGROUND: The presence of heavy metals in food products has become a global
      problem. In order to reduce the absorption of heavy metals from food we should
      consider substances which bind these toxic metals and are generally available and
      easy to apply, such as tannins. OBJECTIVES: The study aimed at verifying if oral
      administration of tannic acid could reduce the accumulation of lead and cadmium
      in the heart and lungs of rats subjected to a continuous exposure of toxic metals
      in low doses. MATERIAL AND METHODS: Adolescent and adult male Wistar rats were
      given tannic acid (2% solution) or distilled water containing 0, 50, 100 mg Pb
      (as (CH3COO)2Pb)/L or 0, 7, 14 mg Cd (as CdCl2)/L, for 6 or 12 weeks. RESULTS:
      Administering a 2% solution of tannic acid alternately with Pb or Cd to the rats
      was the effective method of reducing lead and cadmium content in the rats' heart
      and lungs. CONCLUSIONS: The obtained results may be referred to people. It is
      necessary to conduct further research in order to confirm the hypothesis that
      tannic acid, present in numerous food products and primarily in drinks (wine, tea
      and coffee), used in the human diet, may reduce the accumulation of lead and
      cadmium in the tissues and thus weaken their toxicity, which is important
      regarding our common exposure to heavy metals found in food.

PMID- 24285446
TI  - Protective effects of melatonin and beta-d-glucan against liver injury in rats -
      a comparative study.
AB  - OBJECTIVES: The aim of this study was to investigate the possible protective
      effects of melatonin and beta-d-glucan against ischemia-reperfusion (IR) injury
      in rats. MATERIAL AND METHODS: Forty rats were randomly divided into 5 groups,
      each consisting of 8 animals, as follows. Sham group [S], IR group [C], IR + beta
      Glucan group [beta], IR + melatonin group [MLT], IR + melatonin + beta-Glucan
      group [MLT + beta]. The rats in the C, beta, MLT and MLT + beta groups were
      subjected to IR for 60 min each. Melatonin (10 mg?kg-1) was intraperitoneally
      injected for a single dose 30 min before IR. beta-Glucan (50 mg?kg-1?day-1) was
      orally administered for 10 days to rats. All of the rats were killed on day 11,
      and histological changes in the liver and tissue levels of oxidants and
      antioxidants were evaluated. RESULTS: Malondialdehyde [MDA] level were
      significantly higher in the C group compared to the S group (p = 0.007). MDA
      level were significantly higher in the beta group compared to the MLT and MLT +
      beta groups (p =0.007). Tissue antioxidant markers (superoxide dismut ase [SOD],
      glutathione-peroxidase [GPx], and catalase [CAT]) were significantly lower in the
      C group than the S group (p < 0.05). SOD levels were simply not significant in
      the beta group compared to the MLT and MLT + beta groups. CAT and GPx activities
      were significantly higher in the beta group compared to the MLT and MLT + beta
      groups (p = 0.004).The histological damage ameliorated in beta, MLT and MLT +
      beta groups compared to C group.

PMID- 24285448
TI  - Design, optimization and evaluation of a polymerase chain reaction for detection
      of borrelia spp.
AB  - BACKGROUND: Lyme borreliosis and relapsing fever are important zoonotic diseases
      worldwide and the improvement of diagnostic strategies is a prioritized task
      considering the morbidity of these diseases in some areas. PCR based methods
      appear to be of utmost importance because of the high sensitivity and specificity
      of these assays. OBJECTIVES: To obtain a molecular method based on PCR for the
      detection of the genus Borrelia infection in different specimens. RESULTS: Sets
      of reported primers were evaluated "in silico" and they did not fulfill the
      proposal parameters. On the other hand, the two new, designed sets of primers
      were theoretically efficient for Borrelia DNA amplification. PCR procedures with
      these primers were standardized with borrelial DNA and optimum annealing
      temperatures, primer concentrations and reaction cycle numbers were determined.
      The PCR analytical sensitivity was 10 genomes per reaction for each technique.
      Both PCR were highly specific to different Borrelia species DNA and to samples
      (sera, cerebrospinal liquids and hard ticks) infected artificially with a
      Borrelia strain, visualizing the amplification of the expected DNA fragment. No
      amplification was obtained when other microorganisms were used. 36 human clinical
      samples were negatives in a preliminary study. CONCLUSIONS: Both sets of primers
      with their respective PCR protocols showed similar results, which suggest that
      each one can be used indistinctly in detecting Borrelia spp., mainly in countries
      where the situation of these diseases are unknown.

PMID- 24285447
TI  - Influence of central noradrenergic system lesion on the serotoninergic 5-HT3
      receptor mediated analgesia in rats.
AB  - BACKGROUND: Monoaminergic pathways, impinging an adrenergic and 5-HT3 serotonin
      receptors, modulate nociceptive transmission, but their mechanisms and
      interactions has not been clarified yet. OBJECTIVES: The study was designed to
      investigate the influence of the neonatal noradrenergic system lesion on the
      antinociceptive effect of 5-HT3 receptor ligands assessed in adult animals.
      MATERIAL AND METHODS: Intact male rats were contrasted with rats in which
      noradrenergic nerve terminals were largely destroyed shortly after birth with
      neurotoxin DSP-4 [(N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg * 2
      subcutaneously (sc)], on the 1st and 3rd days of postnatal life. Control animals
      were injected with saline (1.0 mL/kg sc). When the rats attained 10 weeks of age,
      painful reactions were assessed by means of writhing and formalin tests after
      intraperitoneal (ip) administration of 1-phenylbiguanid (FBG; 7.5 mg/kg) or
      ondansetrone (1.0 mg/kg) with FBG (7.5 mg/kg). Morphine was used as a model
      analgesic drug. RESULTS: Injections of morphine (7.5 mg/kg sc) evoked similar
      antinociception in the visceral pain model (writhing test) in both tested groups
      (control and DSP-4). In control rats, a 5-HT3 receptor agonist FBG (7.5 mg/kg)
      elicited analgesia similar to that of morphine but the effect was significantly
      lower in DSP-4 treated animals. A 5-HT3 receptor antagonist ondansetrone (1.0
      mg/kg) injected before FBG did not modify the effect in the control but
      suppressed it in the DSP-4 group. In the formalin test, morphine produced higher
      analgesia in control rats in comparison with the DSP-4 group (pain intensity
      score of 1 point vs. 2-3 points, respectively). Ondansetrone injected before FBG
      alleviated the observed effect. CONCLUSIONS: Based on the obtained results, we
      concluded that the neonatal DSP-4 treatment alters the antinociceptive effects of
      morphine and serotoninergic 5-HT3 receptor ligands. The above may explain altered
      (diminished) reactions of analgesics applied to patients with noradrenergic
      system dysfunction (e.g. depression and/or anxiety disorders).

PMID- 24285449
TI  - Levels of insulin, IL-6 and CRP in patients with unstable angina.
AB  - BACKGROUND: Unstable angina is a condition in which your heart doesn't get enough
      blood flow and oxygen. It may lead to a heart attack. Insulin resistance is
      typically defined as decreased sensitivity or responsiveness to metabolic actions
      of insulin, such as insulin-mediated glucose disposal in skeletal muscle and
      adipose tissue and inhibition of hepatic glucose production. Crosstalk between
      inflammatory signaling pathways and insulin signaling pathways causes metabolic
      insulin resistance and endothelial dysfunction. OBJECTIVES: The present study
      aimed to evaluate the serum levels of pro-inflammatory cytokines and insulin in
      unstable angina patients. MATERIAL AND METHODS: The study included 50 patients
      with unstable angina divided into a female group which contained 16 female
      patients with an age range of 35-73 years, and a male group which contained 34
      male patients with an age range of 40-72 years. Control groups contained forty
      healthy individuals divided into a female group which contained 16 healthy
      females with an age range of 35-73 years, and a male group which contained 24
      males with an age range of 42-72 years. ELISA kits were used to measure insulin,
      IL-6 and CRP. The kits were imported from Biological Company in the United States
      of America. RESULTS: The levels of insulin and IL-6 were considerably elevated
      throughout (p < 0.001), an optimistic relationship concerning insulin with CRP
      and IL-6 in unstable angina patients. CONCLUSIONS: There was increase in the
      level of insulin regarding patients with unsteady angina as a result of insulin
      resistance that was caused by the elevated level of proinflammatory cytokine (IL
      6).

PMID- 24285450
TI  - Salivary lysosomal exoglycosidases profiles in patients with insulin-dependent
      and noninsulin-dependent diabetes mellitus.
AB  - BACKGROUND: In this study we have investigated the effects of type I (insulin
      dependent) and II (non-insulin dependent) diabetes mellitus on the specific
      activity and the output of salivary exoglycosidases: N-acetyl-beta
      hexosoaminidase (HEX), and its isoenzymes A and B (HEX A, HEX B), and beta
      glucuronidase (GLU) in well controlled diabetic patients compared to healthy age
      matched controls. MATERIAL AND METHODS: In the saliva HEX, HEX A, HEX B and GLU
      were determined according to Marciniak et al. Protein was determined by the Lowry
      et al. method. RESULTS: Our results show that in the case of type I diabetes, the
      significantly increased activity of salivary total HEX is mainly due to the
      significantly increased HEX A specific activity. Significantly increased HEX
      specific activity in DM II is an outcome of significantly increased HEX A as well
      as HEX B specific activities in comparison to the appropriate healthy control.
      Our results showed a significant increase in the specific activity of GLU in
      saliva of type II diabetes patients. The output of lysosomal exoglycosidases
      showed a similar significant increase compared to the healthy control, in both
      groups of diabetes mellitus patients. CONCLUSIONS: This study has demonstrated
      that non-insulin dependent diabetes mellitus more strongly modify salivary glands
      glycoconjugates catabolism, which can be attributed to functional and
      morphological changes. A significant increase in the outputs of exoglycosidases
      in saliva of both type diabetes patients once more indicates that special
      attention should be paid to the oral health of these patients.

PMID- 24285451
TI  - Clinical picture of classical, atypical and silent celiac disease in children and
      adolescents.
AB  - BACKGROUND: Celiac disease is a frequent disease of the alimentary tract in
      children. Clinical presentation of the disease is variable and depends on type of
      the disease. OBJECTIVES: The aim of the study was an analysis of clinical
      findings, selected laboratory features and coexisting diseases in children and
      adolescents with celiac disease. MATERIAL AND METHODS: Material of the study
      comprised a series of 78 children aged 8 months - 13 years. Celiac disease was
      diagnosed basing on clinical symptoms, histological studies of intestinal
      specimens and positive serologic tests (EmA, TG2). RESULTS: Classical celiac
      disease was diagnosed in 40 children (51.3%), atypical celiac disease in 26
      children (33.3%) and silent celiac disease in 12 children (15.4%). The most
      frequent clinical symptoms of classical form of celiac disease were chronic
      diarrhea (90.0%), recurrent abdominal pain (70.0%), development retardation
      (65%), hypocholesterolemia (35.0%) and IgA deficiency (22.5%). In atypical form
      of the disease dominated the following symptoms: recurrent abdominal pain
      (76.9%), failure to thrive (38.4%), short stature (42.3%), anemia (15.3%),
      hypertransaminasemia (11.5%), food allergy (19.2%) and thyroid diseases (11.5%).
      In silent celiac disease hypercholesterolemia was present in 33.3%,
      hypertriglycerydemia in 16.6%, type 1 diabetes in 50%, and celiac disease in
      parents or siblings in 33.3%. CONCLUSIONS: Classical celiac disease is the most
      frequently diagnosed clinical form of the disease. Silent celiac disease occurs
      frequently in children with type 1 diabetes mellitus whose parents or siblings
      have celiac disease. Frequent diagnosis of atypical and silent forms of celiac
      disease is an indication to serological examination in children with unclear
      clinical picture and genetic predisposition.

PMID- 24285452
TI  - Clinical and biochemical factors affecting postoperative hypocalcemia after near
      total thyroidectomy.
AB  - BACKGROUND: The most common complication which occurs after thyroidectomy is
      postoperative hypocalcemia due to parathyroid gland damage. It usually appears 24
      48 hours postoperatively, but there are clinical and biochemical factors which
      may contribute to its earlier diagnosis. OBJECTIVES: The aim of this study was to
      assess clinical and biochemical factors which can influence postoperative
      hypocalcemia after near-total thyroidectomy. MATERIAL AND METHODS: The material
      consisted of 103 patients with benign nodular goiter. In all patients the blood
      samples were taken 4 times and levels of total calcium, magnesium, inorganic
      phosphorus, parathormone and thyroid-stimulating hormone were measured. One day
      before surgery and during the first three days postoperatively patients were
      asked about symptoms of hypocalcemia and the presence or absence of a Trousseau
      sign was observed. RESULTS: There was no statistically significant connection
      between the symptoms of hypocalcemia and the age of patients and preoperative
      hyperthyroidism. Patients with symptomatic hypocalcemia had longer operating
      time, resected tissue weighed more and hospitalization time was longer than in
      patients without symptoms of hypocalcemia. Concomitant occurrence of hypocalcemia
      and hypomagnesemia postoperatively was found in 16% of patients. Changes in
      parathyroid hormone concentration measured 10 min after thyroid excision were
      more sensitive and specific for detecting patients with symptomatic hypocalcemia
      after surgery than total calcium concentration. CONCLUSIONS: Measurement of
      intraoperative parathormone level 10 min after thyroidectomy is a highly
      sensitive and specific factor for detecting postoperative hypocalcemia. If we
      connect this parameter with some other clinical features, it will be possible to
      predict postoperative hypocalcemia more accurately and introduce supplementation
      as early as possible.

PMID- 24285453
TI  - Concentration of serum interleukin-27 increase in patients with lymph node
      metastatic gastroesophageal cancer.
AB  - BACKGROUND: Cytokines, one of the key mediators of immune response, play an
      important role in cancer development. OBJECTIVES: The aim of this study was to
      evaluate the interleukin-27 (IL-27) concentration in the serum of patients with
      gastroesophageal cancer (GEC) and in patients with non-cancerous benign diseases
      of the upper digestive tract (NCD). We investigated the relationship between the
      serum IL-27 level and clinicopathological factors, and also the diagnostic
      utility of IL-27 as a marker of GEC presence. Additionally, we evaluated the
      concentrations of serum IL-27 in patients with esophageal squamous cell carcinoma
      before and after surgical tumor resection. MATERIAL AND METHODS: Serum samples
      from 84 GEC patients, 39 NCD patients and 33 healthy subjects were assayed. The
      levels of IL-27, IL-6, IL-12 and IFN-gamma were determined using ELISA kits.
      RESULTS: The serum levels of IL-27 were significantly higher in the GEC patients
      than in the healthy control (p < 0.0001) and in NCD patients (p = 0.006). The
      concentrations of serum IL-27 were related to lymph node status (p = 0.044). ROC
      analysis showed a significant relationship between a high level of serum IL-27
      and GEC presence (AUC = 0.766, p < 0.001). The concentrations of serum IL-27 were
      significantly higher in patients with esophageal squamous cell carcinoma 3 months
      after esophagectomy than before the operation (p = 0.003). CONCLUSIONS: Our
      results demonstrated that a high serum IL-27 level is associated with cancer
      presence and lymph node metastases in GEC. Significantly higher levels of IL-27
      in patients with esophageal squamous cell carcinoma after tumor resection may
      imply that host immune cells are one of the important sources of circulating IL
      27.

PMID- 24285454
TI  - The effect of cardiopulmonary bypass duration on renal injury after congenital
      heart surgery in infants and young children.
AB  - BACKGROUND: Improvements in surgical techniques and perioperative management mean
      that more complex cardiac procedures are being performed on very young patients.
      OBJECTIVES: The aim of this study is to evaluate the effects of the duration of
      cardiopulmonary bypass (CPB) on renal injury after congenital heart surgery in
      infants and young children. MATERIAL AND METHODS: 58 children with ages <= 3
      years undergoing CPB surgery were divided into three groups according to the
      duration of their CPB: Group I was < 90 min, n = 15; Group II, 90-149 min, n =
      25; and Group III was >= 150 min, n = 18. Urinary neutrophil gelatinase
      associated lipocalin, interleukin-18, microalbumin and alpha1-microglobulin were
      measured at baseline and 4 h, 6 h, 12 h and 24 h after surgery. RESULTS: No
      significant differences were noted among the groups in terms of gender, age,
      weight and baseline serum creatinine. The incidence of acute kidney injury (based
      on serum creatinine increase) after surgery were 13.3% (2/15) in Group I, 52.0%
      (13/25) in Group II and 77.8% (14/18) in Group III. 4 children developed acute
      renal failure (ARF) requiring peritoneal dialysis; all of them were in Group III.
      The levels of urinary biomarkers increased significantly, peaked at 4 h and
      remained elevated up to 24 h after surgery. Group III had significantly higher
      levels of urinary biomarkers than Groups I and II at 4-12 h after surgery, while
      the levels were not significantly different at 24 h. CONCLUSIONS: Prolonged CPB
      duration was related to more severe renal tubular injury and acute renal failure.
      Measurements of urinary kidney specific biomarkers in infants and children with a
      CPB duration of more than 150 min might help identify those at high risk for ARF.

PMID- 24285455
TI  - Analysis of the concentrations of interleukin 18 in amniotic fluid in the second
      and the third trimesters of pregnancy.
AB  - BACKGROUND: Interleukin 18 (IL-18) is a glycoprotein produced by macrophages. IL
      18 influences different populations of T lymphocytes and NK cells and stimulates
      the production of INF-gamma by these cells. IL-18 induces both Th1 and Th2
      response. That is why IL-18 is a unique cytokine. OBJECTIVES: The aim of work was
      to examine the concentration of interleukin 18 in amniotic fluid in the 2nd and
      the 3rd trimesters of physiological pregnancies. MATERIAL AND METHODS: 74
      pregnant women were qualified to take part in the studies. The amniotic fluid
      samples by amniocentesis were taken from the patients. Two groups were
      distinguished among the examined patients: group I - 45 pregnant women qualified
      for genetic amniocentesis between the 15th and 19th week of pregnancy. All
      findings of the cytogenetic tests were normal. Group II: 29 pregnant women in
      their 3rd trimester were qualified for diagnostic amniocentesis in order to
      determine the biological maturity of the fetuses. The concentration of IL-18 was
      marked with the immunoenzymatic method ELISA with the use of the kit produced by
      the MBL company. Method sensitivity was < 12.5 pg/mL. RESULTS: In the 2nd
      trimester of pregnancy the average concentration of IL-18 in the amniotic fluid
      was 454.69 pg/mL and in the 3rd trimester was 71.73 pg/mL. The obtained data
      proved that the average concentration of IL-18 in the 2nd trimester was
      significantly higher than in the 3rd trimester. The obtained differences in the
      findings were statistically significant (p < 0.05). CONCLUSIONS: The presence and
      high levels of IL-18 in the amniotic fluid in the 2nd trimester of pregnancy
      indicate an early process of initiation of immunological mechanisms by the fetus.
      An average concentration of IL-18 in the amniotic fluid was significantly higher
      in the 2nd trimester of pregnancy than in the 3rd trimester, which may indicate
      the influential role of IL-18 on the development of the immune response in the
      fetus in this period of gestation.

PMID- 24285456
TI  - Multislice computed tomography angiography as an imaging modality of choice in
      patients with suspicion of pulmonary embolism - own experiences and modern
      imaging techniques.
AB  - BACKGROUND: Pulmonary embolism (PE) is a relatively common and potentially life
      threatening clinical condition with estimated prevalence to be 0.4%. Early
      diagnosis of PE followed by adequate treatment reduces the risk of major
      complications. Multislice computed tomography pulmonary angiography (CTPA)
      currently constitutes an imaging modality of choice in patients with suspicion of
      PE. Computed tomography venography (CTV) of lower limb veins and CTPA can be
      performed simultaneously, allowing for visualization of lower limb deep vein
      thrombosis (DVT). Additionally, dual energy CT scanners enable the evaluation of
      lung perfusion which is of high value in indirect detection of pulmonary arterial
      microembolisms. OBJECTIVES: The goal of the study was to assess the diagnostic
      value of a 64-detector CT scanner in the detection of both acute and chronic PE
      in patients with clinical suspicion of PE based on clinical scores. MATERIAL AND
      METHODS: Retrospective analysis of CTPA performed between 2010 and 2012 in 102
      consecutive patients (64 women, 38 men) with clinical suspicion of PE based on
      clinical scores (first of all the Wells score) and elevated D-dimer level was
      carried out. The patients' median age was 68.9 (range between 34 and 91). The
      examinations were carried out with a 64-detector CT scanner, using a "pulmonary
      embolism" protocol. The volume of contrast agent ranged from 60 to 70 mL,
      depending on the patient's body mass. The contrast medium was administered with
      an injection rate 4.0-5.0 mL/s. The concentration of the contrast medium in the
      main pulmonary artery (MPA) was monitored in every case with the use of a 'smart
      prep' method. Scanning was started a few seconds (4-6) after reaching a plateau
      by the contrast medium in MPA. Additionally, in selected patients CTV was
      performed and/or lung perfusion was evaluated. RESULTS: Evidence of PE was
      demonstrated in 32 of 102 (31.4%) analyzed patients (pts). In 19 patients,
      centrally localized clots were visualized. Additionally, in 32 patients, lobar,
      segmental and proximal subsegmental filling defects corresponding to thrombo
      embolic material were demonstrated. Moreover, in 14 patients, distal subsegmental
      filling defects were shown. Alternative diagnoses included: heart failure-related
      congestion (21 pts), pneumonia (19 pts) and malignancy (5 pts). CONCLUSIONS: The
      multislice CTPA is an extremely useful imaging modality in patients with clinical
      suspicion of PE. The examination enables not only the analysis of pulmonary
      vessels but also evaluation of pulmonary parenchyma and mediastinum. The
      collimation of 0.625 mm makes it possible to detect the small foci of peripheral
      embolism.

PMID- 24285457
TI  - Effectiveness and safety of topical emollients in the treatment of PUVA-induced
      pruritus.
AB  - BACKGROUND: In this study we tried to assess the efficacy of topical emollients
      in the treatment of patients with PUVA-induced pruritus. MATERIAL AND METHODS: 41
      patients over 18 years of age, who received PUVA treatment in the phototherapy
      unit, were included in the study. Patients were randomly divided into two groups;
      Group I was administered with a 4% urea lotion and Group II was administered with
      liquid petrolatum. The follow-up period was minimum 4 weeks. During the first 2
      weeks, patients were administered topical emollients and received PUVA treatment
      together. The next 2 weeks, they continued PUVA treatment without any medication.
      RESULTS: When time-dependent changes in the visual analogue scale scores for
      pruritus of both groups were considered, both treatment methods were found to be
      remarkably successful (p < 0.0001). In addition, an insignificant group-time
      interaction was identified (p = 0.753). CONCLUSIONS: Topical emollients were
      found to be effective in the treatment of PUVA-induced pruritus. Both forms of
      medication can be successfully administered and increase the patient's compliance
      with medication.

PMID- 24285458
TI  - The impact of specialized physiotherapy methods on BODE index in COPD patients
      during hospitalization.
AB  - OBJECTIVES: To evaluate the effectiveness of specialized physiotherapy methods
      measured by the BODE index in patients with COPD during hospitalization. MATERIAL
      AND METHODS: The study was conducted on a group of 30 patients diagnosed with
      COPD, all under treatment at the clinical hospital in Wroclaw due to the
      exacerbation of their symptoms. All patients were undergoing standard
      pharmacological treatment along with basic physiotherapy. The subjects of the
      study were randomly divided between an experimental group of 20 persons and a
      control group of 10 persons. Patients in the experimental group underwent a
      series of 6 additional massage treatments performed over a period of a few days,
      aimed at reshaping the following muscles: the sterno-cleidomastoid, pectoralis
      major, pectoralis minor, trapezius, levator scapulae, rhomboids and serratus
      anterior. Each massage lasted for 30 minutes and consisted of stroking, grinding,
      vibration and kneading techniques. Before and after therapy the patients were
      assessed based on the BODE index. First, the patient's BMI was calculated (B).
      Airflow obstruction (O) was determined by the percentage value of FEV1 while the
      MRC scale was used to evaluate a patient's dyspnea (D). Exercise capacity (E) was
      measured by the distance a patient could cover in a 6-minute walk test. Each
      variable of the BODE index was ranked on a scale from 0 to 3 points except the
      BMI, for which was given either 0 or 1 point. RESULTS: Analysis of the results
      showed a significant improvement of the BODE index in the experimental group
      while in the control group this ratio changed slightly. The FEV1 and MRC
      parameters changed significantly only in the experimental group. CONCLUSIONS:
      After a week of therapy the BODE index improved in both groups, but in the
      experimental group there was a significantly higher difference. In the
      experimental group all BODE components except BMI improved highly significantly,
      whereas in the control group only exercise capacity was significantly improved.

PMID- 24285459
TI  - Associations between results of post-stroke NDT-Bobath rehabilitation in gait
      parameters, ADL and hand functions.
AB  - BACKGROUND: In patients after a stroke there are variable disorders. These
      patients often need rehabilitation in more than one area beceause of multiple
      limitations of the ability to perform everyday activities. OBJECTIVES: The aim of
      the study was to assess correlations - statistical relationships between observed
      gait parameters, ADL and hand functions - results of rehabilitation of patients
      after ischaemic stroke according to the NDTBobath method for adults. MATERIAL AND
      METHODS: The investigated group consisted of 60 patients after ischaemic stroke,
      who participated in the rehabilitation programme. 10 sessions of the NDT-Bobath
      therapy were provided in 2 weeks (10 days of the therapy). The calculation of
      correlations was made based on changes of parameters: Bobath Scale (to assess
      hand functions), Barthel Index (to assess ADL), gait velocity, cadence and stride
      lenght. Measurements were performed in every patient twice: on admission (before
      the therapy) and after last session of the therapy to assess rehabilitation
      effects. RESULTS: The main statistically relevant corellations observed in the
      study were as follows: in the whole group of patients: poor and moderate
      (negative) correlation between changes of gait parameters and Bobath Scale and
      Barthel Index, moderate and severe (negative) correlation between changes of gait
      parameters and Bobath Scale and Barthel Index in the group of women, correlation
      between changes in Bobath Scale and Barthel Index in the group of patients with
      left side of paresis, (negative) correlation between changes of gait parameters
      and Bobath Scale in group of patients younger than 68 years, moderate, high and
      very high correlations between changes in gait parameters in groups of women,
      men, younger than 68 years and older than 68 years. CONCLUSIONS: There have been
      observed statistically significant and favourable changes in the health status of
      patients, described by gait parameters, changes in hand functions and ADL. Based
      on the presented correlations there is an assumption that it is hard to achieve
      simultaneous recovery in all areas: gait parameters, hand functions and ADLs in
      two weeks of rehabilitation.

PMID- 24285460
TI  - The biological role of carnosine and its possible applications in medicine.
AB  - The article reviews current literature on the biological role of carnosine, its
      properties and use as a supplement in periods of intense physical activity.
      Studies carried out on laboratory animals and humans have shown that carnosine
      can have a beneficial influence on the organism. Carnosine is found naturally
      mainly in the skeletal muscles, central nervous system, olfactory neurons and in
      the lens of the eye in some vertebrates, including humans. Due to its
      antioxidant, protective, chelating, anti-glycation activity, this dipeptide can
      be used to prevent and treat diseases such as diabetes, neurodegenerative
      diseases, diseases of the sense organs and cancers. It may also cure or alleviate
      many other disorders thanks to its wide spectrum of activity. Carnosine is
      already used by athletes to achieve better results, due to its buffering feature,
      which contributes to the maintenance of the acid-base balance in the muscles.
      Future studies on the influence of carnosine on the human organism may lead to
      the therapeutic use of this dipeptide for many diseases, in addition to improving
      both amateur and professional athletes' results. 

PMID- 24285461
TI  - The effect of endothelin-1 on pancreatic diseases in patients who smoke.
AB  - Endothelin (ET) is a peptide secreted by the endothelial cells of blood vessels.
      It has a very strong vasoconstricting effect. Endothelin-1 (ET-1) is present in
      the blood in low concentrations, but in response to the stimulus of cigarette
      smoking, it can be released into the interior of blood vessels in substantial
      quantities, resulting in rapid vasoconstriction. ET-1 activity causes ischemia
      and hypoxia in many organs, particularly in the pancreas. The destructive action
      of tobacco smoke components on the cells of the pancreas is known, but so far the
      mechanisms of these changes are not fully understood. It has been suggested that
      ET-1 may play a major role in this process. By inducing vasoconstriction in the
      pancreas, with a subsequent disruption in its blood flow, ET-1 leads to
      structural changes in this organ and to exocrine and endocrine dysfunction. ET-1
      also has the ability to induce secretion of pro-inflammatory cytokines (IL-1, IL
      6), which intensify existing pancreatitis and lead to the progression of this
      disease. ET-1 can stimulate collagen production in the pancreas, which
      contributes to the formation of fibrosis in patients with chronic pancreatitis.
      Nicotine from tobacco smoke intensifies insulin resistance in patients with
      diabetes. High insulin concentrations induce the secretion of ET-1 by the
      endothelial cells of the pancreas. By inducing vasoconstriction and subsequent
      tissue hypoxemia, ET-1 can cause a decrease in peripheral glucose utilization and
      contribute to the progression of type 2 diabetes. ET-1 is considered a risk
      factor for pancreatic diseases, particularly acute ischemia and pancreatitis. 

PMID- 24285462
TI  - Inability to have children caused by recurrent HELLP syndrome in early
      pregnancies - implications for a review of literature.
AB  - This review is inspired by a case of two pregnancies of the same patient
      complicated by HELLP syndrome, which suggests that there is a predisposition for
      the occurrence of preeclampsia and HELLP syndrome in early pregnancy. HELLP
      syndrome, uncommon below the 20th week and rarer still in two consecutive
      pregnancies, appeared in two pregnancies of the same woman. The aim of our work
      is to try to understand the cause of heterogeneity of HELLP syndrome and help
      find a way of prolonging such pregnancies. Recurrent HELLP syndrome in early
      pregnancy is a form of severe, fulminant preeclampsia. The preceding symptom is a
      surge in blood pressure. The hypertension becomes resistant to antihypertensive
      drugs, which indicates that preexisting hypertension is later accompanied by
      other factors contributing to the rise in blood pressure. Different effects of
      high dosage of corticosteroids on liver and platelets show that there are
      different factors responsible for liver damage and for thrombocytopenia. It seems
      that the symptoms have various origins, so the therapy with one drug only is not
      sufficiently effective. Nicotine analogues or a plant extract (from rootstock of
      Eriosema kraussianum) used by South African traditional healers for erectile
      dysfunction seem to give a chance of prolonging pregnancy and, consequently,
      having children. 

PMID- 24285463
TI  - The therapeutic effect of probiotic bacteria on gastrointestinal diseases.
AB  - The cause of many gastrointestinal diseases, such as irritable bowel syndrome,
      chronic inflammatory bowel disease: inflammatory and necrotizing enterocolitis or
      diarrhea: infectious, traveler's diarrhea, and diarrhea caused by antibiotic
      treatment is an imbalance of intestinal microflora. Probiotics are live
      microorganisms, which administered in sufficient quantities, have beneficial
      health effects. The phenomenon of eating probiotic products started 100 years
      ago, when the first reports showed beneficial effects of probiotic bacteria on
      human health. Since then, probiotic preparations have become an essential element
      in the prevention and treatment of certain diseases. Currently, probiotics are of
      the utmost importance in supporting the treatment of gastrointestinal diseases
      and autoimmune disorders. Probiotic microorganisms are primarily lactic acid
      producing bacteria of the general Lactobacillus, Bifidobacterium. Many studies
      have confirmed the beneficial effects of probiotics, particularly in the
      treatment of acute diarrhea. This applies in particular to diarrhea of viral
      etiology, especially in infants and young children. 

PMID- 24285464
TI  - hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and
      migration.
AB  - Expression of the transmembrane-4-L-six-family-1 (TM4SF1) is high in human
      pancreatic cancer cells, but the underlying mechanism remains unclear. In this
      study, we aimed to identify and characterize microRNAs that regulate TM4SF1
      expression in PC cells. Western blot analysis and quantitative polymerase chain
      reaction were used to detect TM4SF1 and hsa-miR-141 levels in four PC cell lines.
      SW1990 and BxPc-3 cells were transfected with the inhibitor miR-141, the
      inhibitor negative control, the miR-141 mimic and the mimic negative control; and
      cell invasion, migration, proliferation, cell cycle progression and apoptosis
      were detected by Transwell, MTT and flow cytometry assays, respectively. The miR
      141 levels negatively correlated with the TM4SF1 protein levels in PC cells. The
      TM4SF1 protein levels were lower in the 141M group but higher in the 141I group,
      although the TM4SF1 mRNA levels had no significant changes, compared to the
      negative controls. Luciferase assays demonstrated that hsa-miR-141 directly
      targeted the 3'-untranslated region of the TM4SF1 gene. In addition, miR-141
      downregulated TM4SF1 expression to inhibit invasion and migration of PC cells but
      had no effects on cell proliferation, cell cycle progression or apoptosis. TM4SF1
      is a direct target of miR-141. Our findings that TM4SF1 expression was inhibited
      by miR-141 provide new insights into the oncogenic mechanism of TM4SF1 and
      suggest that miR-141 represents a novel molecular target for PC therapy.

PMID- 24285465
TI  - Diaminocyclopropenylidene organocatalysts: beyond N-heterocyclic carbenes.
AB  - Cyclopropenylidene carbenes have been found to be efficient catalysts for the
      intermolecular Stetter reaction between aromatic aldehydes and alpha,beta
      unsaturated ketones. In this transformation, the cyclopropenylidene proved
      superior to more traditional thiazolium- and triazolium-derived carbenes.
      Preparation and evaluation of a chiral analogue have also been reported. 

PMID- 24285466
TI  - Joint model of recurrent events and a terminal event with time-varying
      coefficients.
AB  - Joint modeling of recurrent events and a terminal event has been studied
      extensively in the past decade. However, most of the previous works assumed
      constant regression coefficients. This paper proposes a joint model with time
      varying coefficients in both event components. The proposed model not only
      accommodates the correlation between the two type of events, but also
      characterizes the potential time-varying covariate effects. It is especially
      useful for evaluating long-term risk factors' effect that could vary with time. A
      Gaussian frailty is used to model the correlation between event times. The
      nonparametric time-varying coefficients are modeled using cubic splines with
      penalty terms. A simulation study shows that the proposed estimators perform
      well. The model is used to analyze the readmission rate and mortality jointly for
      stroke patients admitted to Veterans Administration (VA) Hospitals. 

PMID- 24285467
TI  - Can building evidence move a persistent vaccine safety concern?

PMID- 24285468
TI  - Acetaminophen receipt among HIV-infected patients with advanced hepatic fibrosis.
AB  - PURPOSE: HIV-infected patients may be at particular risk for acetaminophen
      induced hepatotoxicity, but acetaminophen use in the context of liver injury has
      been incompletely examined among HIV-infected patients. Among a sample of HIV
      infected patients, we aimed to determine acetaminophen exposure, assess the cross
      sectional association between acetaminophen exposure and advanced hepatic
      fibrosis, and determine whether factors associated with acetaminophen exposure
      varied by HCV status. METHODS: We conducted a cross-sectional analysis of the
      Veterans Aging Cohort Study. Advanced hepatic fibrosis was defined as a FIB-4 >
      3.25, a composite score calculated based on age, alanine aminotransferase,
      aspartate aminotransferase, and platelet count. Multivariable ordered polytomous
      logistic regression was used to determine the association between FIB-4 status
      and acetaminophen exposure stratified by HCV status. RESULTS: Among HIV-infected
      patients (n = 14 885), 31% received at least one acetaminophen prescription.
      Among those receiving acetaminophen, acetaminophen overuse was common among both
      HIV-monoinfected and HIV/HCV-coinfected patients (846 [31%] vs 596[32%], p =
      0.79). After stratifying by HCV status, those with evidence of advanced liver
      fibrosis were equally likely to be exposed to acetaminophen. Furthermore, HIV
      monoinfected patients with an alcohol use disorder were more likely to have
      acetaminophen overuse (OR [95%CI] = 1.56 [1.21-2.02]). CONCLUSIONS: Strategies to
      minimize acetaminophen exposure, especially for HIV-monoinfected patients, are
      warranted.

PMID- 24285469
TI  - Label-free virus identification and characterization using electrochemical
      impedance spectroscopy.
AB  - We demonstrate here the application of electrochemical impedance spectroscopy
      (EIS) in microfluidic devices for label-free virus identification by means of
      their specific "signature" and also investigate its feasibility for titer
      quantitation using two basic approaches. The first one is a method based on
      identifying so-called "resonance" frequencies manifesting in our microdevices and
      monitoring their variation as a function of the virus concentration, whereas the
      second one relies on measuring the relative impedance variation at these
      "resonance" frequencies. Best results have been obtained for the highest
      "resonance" frequency (~80 MHz), which we attribute to be due to both the
      structure of the microdevice and the extremely small size of the viruses that
      make their effect significant only at such frequencies. This is a simpler method
      of determining virus concentration in diluted solutions of purified viruses than
      the well-established traditional plaque assay titer estimation method, and-since
      it is based on frequency measurement-could potentially be more accurate. 

PMID- 24285471
TI  - Lithography-free approach to highly efficient, scalable SERS substrates based on
      disordered clusters of disc-on-pillar structures.
AB  - We present a lithography-free technological strategy that enables fabrication of
      large area substrates for surface-enhanced Raman spectroscopy (SERS) with
      excellent performance in the red to NIR spectral range. Our approach takes
      advantage of metal dewetting as a facile means to create stochastic arrays of
      circular patterns suitable for subsequent fabrication of plasmonic disc-on-pillar
      (DOP) structures using a combination of anisotropic reactive ion etching (RIE)
      and thin film deposition. Consistent with our previous studies of individual DOP
      structures, pillar height which, in turn, is defined by the RIE processing time,
      has a dramatic effect on the SERS performance of stochastic arrays of DOP
      structures. Our computational analysis of model DOP systems confirms the strong
      effect of the pillar height and also explains the broadband sensitivity of the
      implemented SERS substrates. Our Raman mapping data combined with SEM structural
      analysis of the substrates exposed to benzenethiol solutions indicates that
      clustering of shorter DOP structures and bundling of taller ones is a likely
      mechanism contributing to higher SERS activity. Nonetheless, bundled DOP
      structures appeared to be consistently less SERS-active than vertically aligned
      clusters of DOPs with optimized parameters. The latter are characterized by
      average SERS enhancement factors above 10(7). 

PMID- 24285470
TI  - Cortical inputs innervate calbindin-immunoreactive interneurons of the rat
      basolateral amygdaloid complex.
AB  - The present study was undertaken to shed light on the synaptic organization of
      the rat basolateral amygdala (BLA). The BLA contains multiple types of GABAergic
      interneurons that are differentially connected with extrinsic afferents and other
      BLA cells. Previously, it was reported that parvalbumin immunoreactive (PV(+) )
      interneurons receive strong excitatory inputs from principal BLA cells but very
      few cortical inputs, implying a prevalent role in feedback inhibition. However,
      because prior physiological studies indicate that cortical afferents do trigger
      feedforward inhibition in principal cells, the present study aimed to determine
      whether a numerically important subtype of interneurons, expressing calbindin
      (CB(+) ), receives cortical inputs. Rats received injections of the anterograde
      tracer Phaseolus vulgaris-leucoagglutinin (PHAL) in the perirhinal cortex or
      adjacent temporal neocortex. Light and electron microscopic observations of the
      relations between cortical inputs and BLA neurons were performed in the lateral
      (LA) and basolateral (BL) nuclei. Irrespective of the injection site (perirhinal
      or temporal neocortex) and target nucleus (LA or BL), ~90% of cortical axon
      terminals formed asymmetric synapses with dendritic spines of principal BLA
      neurons, while 10% contacted the dendritic shafts of presumed interneurons, half
      of which were CB(+) . Given the previously reported pattern of CB coexpression
      among GABAergic interneurons of the BLA, these results suggest that a subset of
      PV-immunonegative cells that express CB, most likely the somatostatin-positive
      interneurons, are important mediators of cortically evoked feedforward inhibition
      in the BLA.

PMID- 24285473
TI  - Recovery of biological active catechol-O-methyltransferase isoforms from Q
      sepharose.
AB  - The development of new catechol-O-methyltransferase inhibitors has led to an
      improvement in the treatment of Parkinson's disease. However, despite the fact
      that the soluble isoform has been extensively investigated, few studies have been
      published concerning membrane isoform chromatographic recovery and bioactivity
      levels. In this work, chromatographic profiles of both catechol-O
      methyltransferase isoforms were compared using quaternary amine as a ligand to
      evaluate its activity levels and recovery rates. Results show that both proteins
      required different conditions for adsorption; the soluble isoform adsorption was
      performed at low ionic strength, while the membrane isoform required increasing
      linear salt gradient. However, the application of 0.5% Triton X-100 promoted
      membrane isoform adsorption even at low ionic strength. Indeed, chromatographic
      conditions of both isoforms became similar when detergents were applied. The
      developed methods also appear to be highly effective in bioactivity recovery,
      presenting rates of 107% for soluble protein and 67 and 91% for membrane isoform
      without and with detergents, respectively. The chromatographic strategies with
      and without detergents resulted in a 4.3- and sevenfold purification,
      respectively, corresponding to specific activity values of 331 and 496 nmol/h/mg.
      Thus, the use of Q-sepharose as anion exchanger was effective in the recovery of
      both enzymes, which is a requirement for further kinetic and pharmacological
      trials.

PMID- 24285474
TI  - Preclinical evaluation of holmium-166 labeled anti-VEGF-A(Bevacizumab).
AB  - Radiolabeled antiangiogenic monoclonal antibodies are potential agents for
      targeted therapy in specific types of malignancies. In this study, (166)Ho-DOTA
      Bevacizumab was used in biodistribution studies using single-photon emission
      computed tomography (SPECT) to acquire dosimetric aspects of the radiolabeled
      antibody in mice. The liver toxicity of the radiolabeled antibody was also
      determined using serum glutamic pyruvic transaminase, serum glutamic oxaloacetic
      transaminase and alkaline phosphatase assay 2-7 days post-injection. The SPECT
      biodistribution demonstrated a similar pattern as the other radiolabeled anti
      vascular endothelial growth factor A (VEGF-A) immunoconjugates. (166)Ho-DOTA
      Bevacizumab was revealed as a potential compound for therapy/imaging of VEGF-A
      expression in oncology.

PMID- 24285472
TI  - A comparison of the folding kinetics of a small, artificially selected DNA
      aptamer with those of equivalently simple naturally occurring proteins.
AB  - The folding of larger proteins generally differs from the folding of similarly
      large nucleic acids in the number and stability of the intermediates involved. To
      date, however, no similar comparison has been made between the folding of smaller
      proteins, which typically fold without well-populated intermediates, and the
      folding of small, simple nucleic acids. In response, in this study, we compare
      the folding of a 38-base DNA aptamer with the folding of a set of equivalently
      simple proteins. We find that, as is true for the large majority of simple,
      single domain proteins, the aptamer folds through a concerted, millisecond-scale
      process lacking well-populated intermediates. Perhaps surprisingly, the observed
      folding rate falls within error of a previously described relationship between
      the folding kinetics of single-domain proteins and their native state topology.
      Likewise, similarly to single-domain proteins, the aptamer exhibits a relatively
      low urea-derived Tanford beta, suggesting that its folding transition state is
      modestly ordered. In contrast to this, however, and in contrast to the behavior
      of proteins, phi-value analysis suggests that the aptamer's folding transition
      state is highly ordered, a discrepancy that presumably reflects the markedly more
      important role that secondary structure formation plays in the folding of nucleic
      acids. This difference notwithstanding, the similarities that we observe between
      the two-state folding of single-domain proteins and the two-state folding of this
      similarly simple DNA presumably reflect properties that are universal in the
      folding of all sufficiently cooperative heteropolymers irrespective of their
      chemical details. 

PMID- 24285475
TI  - Syntheses of deuterium labeled prenyldiphosphate and prenylcysteine analogues for
      in vivo mass spectrometric quantification.
AB  - A Wittig reaction employing Li(CD3)2CP(C6H5)3 was used to prepare d6-farnesol and
      d6-geranylgeraniol. Reductive amination of aniline-2,3,4,5,6-d5 was used to
      prepare the unnatural isoprenoid analogues d5-anilinogeraniol and d5
      anilinofarnesol. All of these deuterated isoprenols were elaborated into their
      diphosphate and cysteine thioether derivatives suitable for use as stable-isotope
      labeled standards for quantitative mass spectrometric analysis.

PMID- 24285476
TI  - Synthesis of [1,3, NH2-(15)N3] (5'S)-8,5'-cyclo-2'-deoxyguanosine.
AB  - To facilitate NMR studies and low-level detection in biological samples by mass
      spectrometry, [1,3, NH2-(15)N3] (5'S)-8,5'-cyclo-2'-deoxyguanosine was
      synthesized from imidazole-4,5-dicarboxylic acid in 21 steps. The three (15)N
      isotopes were introduced during the chemo-enzymatic preparation of [1,3, NH2
      (15)N3]-2'-deoxyguanosine using an established procedure. The (15)N-labeled 2'
      deoxyguanosine was converted to a 5'-phenylthio derivative, which allowed the 8
      5' covalent bond formation via photochemical homolytic cleavage of the C-SPh
      bond. SeO2 oxidation of C-5' followed by sodium borohydride reduction and
      deprotection gave the desired product in good yield. The isotopic purity of the
      [1,3, NH2-(15)N3] (5'S)-8,5'-cyclo-2'-deoxyguanosine was in excess of 99.94 atom%
      based on liquid chromatography-mass spectrometry measurements.

PMID- 24285477
TI  - A novel no-carrier-added submicromolar scale radiosynthesis of [S-methyl-14C]
      florfenicol.
AB  - In this paper is reported a novel reaction scheme for the no-carrier-added
      submicromolar scale radiosynthesis of [S-methyl-(14)C]-florfenicol that has been
      newly designed, developed and employed by us successfully. The [(14)C]-product
      was obtained in an overall radiochemical yield of 30% based on [(14)C]-methyl
      iodide taken for the reaction with a radiochemical purity of more than 96%. The
      specific activity of the product was ~50 mCi (1.85 GBq)/mmol. Chlorosulfonation
      of compound I was followed by sodium salt formation in situ and it was succeeded
      by the introduction of [(14)C]-methyl group by coupling with [(14)C]-CH3 I.
      Subsequently, the oxazolidin-2-one protecting group was opened up by a reaction
      with sulfuric acid in dioxane and later, the amino group was dichloroacetylated
      with methyl-2,2-dichloroacetate in triethylamine to obtain [S-methyl-(14)C]
      florfenicol.

PMID- 24285478
TI  - 19F/18F exchange synthesis for a novel [18F]S1P3-radiopharmaceutical.
AB  - (19)F/(18)F isotope exchange is a useful method to label drug molecules
      containing (19)F-fluorine with (18)F without modifying the drug molecule itself.
      Sphingosine-1-phosphate (S1P) is an important cellular mediator that functions by
      signaling through cell surface receptors. S1P is involved in several cell
      responses and may be related to many central nervous system disorders, including
      neural malfunction in Alzheimer's disease. In this study, [(18)F]1-benzyl-N-(3,4
      difluorobenzyl)-2-isopropyl-6-(2-methoxyethoxy)-1H-indole-3-carboxamide, a novel
      (18)F-labeled positron emission tomography tracer for the S1P3 receptor, was
      successfully synthesized using the (19)F/(18)F isotope exchange reaction.
      Parameters of the reaction kinetics were studied, and correlations between the
      initial (18)F-activity, the amount of precursor, radiochemical yield and specific
      activity (SA) were determined. Contrary to expectations, high initial (18)F
      activity decreased the radiochemical yield, and only a minor increase of SA
      occurred. This is most probably due to the complexity of the molecule and the
      subsequent susceptibility to radiolytic bond disruption. On the basis of the
      present results, a convenient condition for the (19)F/(18)F exchange reaction is
      the use of 2 umol precursor with 20 GBq of (18)F-activity. This afforded a
      radiochemical yield of ~10% with an SA of 0.3 GBq/umol. Results from this study
      are of interest for new tracer development where high initial (18)F-activity and
      (19)F/(18)F isotope exchange is used.

PMID- 24285479
TI  - Biodistribution of 99mTc-sunitinib as a potential radiotracer for tumor hypoxia
      imaging.
AB  - Tyrosine kinases are groups of enzymes, which are over-expressed in solid tumor
      cells, representing good targets for different drugs such as sunitinib (N-[2
      (diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3
      ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide). The aim of this work was
      to design and synthesize (99m)Tc-sunitinib radiotracer and to study its tumor
      binding specificity as a novel selective radiopharmaceutical for tumor hypoxia
      imaging. The in vivo biodistribution of (99m)Tc-sunitinib in tumor bearing mice
      showed high target/non-target (T/NT) ratio (T/NT ~ 3 at 60 min post injection).
      This preclinical high biological accumulation in tumor cells suggests that
      (99m)Tc-sunitinib is ready to go through the clinical trials as a potential
      selective radiotracer able to image tumor hypoxia.

PMID- 24285481
TI  - The Affordable Care Act as translational research.

PMID- 24285483
TI  - HIV-1 Vpr induces adipose dysfunction in vivo through reciprocal effects on
      PPAR/GR co-regulation.
AB  - Viral infections, such as HIV, have been linked to obesity, but mechanistic
      evidence that they cause adipose dysfunction in vivo is lacking. We investigated
      a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which
      can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome
      proliferator-activated receptor gamma (PPARgamma) in vitro, in HIV-associated
      adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients
      tested, including those on antiretroviral therapy (ART) with undetectable viral
      load. Vpr-mediated mechanisms were dissected in vivo using mouse models
      expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused
      with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis,
      hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots
      in these mice had diminished mass, macrophage infiltration, and blunted PPARgamma
      target gene expression but increased GR target gene expression. In liver, we
      observed blunted PPARalpha target gene expression, steatosis with decreased
      adenosine monophosphate-activated protein kinase activity, and insulin
      resistance. Similar to human HIV-infected patients, Vpr circulated in the serum
      of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle
      arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally
      altered association of PPARgamma and GR with their target promoters. These
      results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in
      tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle
      control to produce adipose dysfunction and hepatosteatosis. Confirmation of these
      mechanisms in HIV patients could lead to targeted treatment of the metabolic
      complications with Vpr inhibitors, GR antagonists, or PPARgamma/PPARalpha
      agonists. 

PMID- 24285484
TI  - Real-time, aptamer-based tracking of circulating therapeutic agents in living
      animals.
AB  - A sensor capable of continuously measuring specific molecules in the bloodstream
      in vivo would give clinicians a valuable window into patients' health and their
      response to therapeutics. Such technology would enable truly personalized
      medicine, wherein therapeutic agents could be tailored with optimal doses for
      each patient to maximize efficacy and minimize side effects. Unfortunately,
      continuous, real-time measurement is currently only possible for a handful of
      targets, such as glucose, lactose, and oxygen, and the few existing platforms for
      continuous measurement are not generalizable for the monitoring of other
      analytes, such as small-molecule therapeutics. In response, we have developed a
      real-time biosensor capable of continuously tracking a wide range of circulating
      drugs in living subjects. Our microfluidic electrochemical detector for in vivo
      continuous monitoring (MEDIC) requires no exogenous reagents, operates at room
      temperature, and can be reconfigured to measure different target molecules by
      exchanging probes in a modular manner. To demonstrate the system's versatility,
      we measured therapeutic in vivo concentrations of doxorubicin (a
      chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole
      blood for several hours with high sensitivity and specificity at subminute
      temporal resolution. We show that MEDIC can also obtain pharmacokinetic
      parameters for individual animals in real time. Accordingly, just as continuous
      glucose monitoring technology is currently revolutionizing diabetes care, we
      believe that MEDIC could be a powerful enabler for personalized medicine by
      ensuring delivery of optimal drug doses for individual patients based on direct
      detection of physiological parameters. 

PMID- 24285485
TI  - The tongue enables computer and wheelchair control for people with spinal cord
      injury.
AB  - The Tongue Drive System (TDS) is a wireless and wearable assistive technology,
      designed to allow individuals with severe motor impairments such as tetraplegia
      to access their environment using voluntary tongue motion. Previous TDS trials
      used a magnetic tracer temporarily attached to the top surface of the tongue with
      tissue adhesive. We investigated TDS efficacy for controlling a computer and
      driving a powered wheelchair in two groups of able-bodied subjects and a group of
      volunteers with spinal cord injury (SCI) at C6 or above. All participants
      received a magnetic tongue barbell and used the TDS for five to six consecutive
      sessions. The performance of the group was compared for TDS versus keypad and TDS
      versus a sip-and-puff device (SnP) using accepted measures of speed and accuracy.
      All performance measures improved over the course of the trial. The gap between
      keypad and TDS performance narrowed for able-bodied subjects. Despite
      participants with SCI already having familiarity with the SnP, their performance
      measures were up to three times better with the TDS than with the SnP and
      continued to improve. TDS flexibility and the inherent characteristics of the
      human tongue enabled individuals with high-level motor impairments to access
      computers and drive wheelchairs at speeds that were faster than traditional
      assistive technologies but with comparable accuracy. 

PMID- 24285487
TI  - TB or not TB: that is no longer the question.
AB  - Tuberculosis (TB) remains a devastating infectious disease and, with the
      emergence of multidrug-resistant forms, represents a major global threat. Much of
      our understanding of pathogenic and immunologic mechanisms in TB has derived from
      studies in experimental animals. However, it is becoming increasingly clear in TB
      as well as in other inflammatory diseases that there are substantial differences
      in immunological responses of humans not found or predicted by animal studies.
      Thus, it is critically important to understand mechanisms of pathogenesis and
      immunological protection in humans. In this review, we will address the key
      immunological question: What are the necessary and sufficient immune responses
      required for protection against TB infection and disease in people-specifically
      protection against infection, protection against the establishment of latency or
      persistence, and protection against transitioning from latent infection to active
      disease. 

PMID- 24285486
TI  - Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc
      receptor for oral delivery.
AB  - Nanoparticles are poised to have a tremendous impact on the treatment of many
      diseases, but their broad application is limited because currently they can only
      be administered by parenteral methods. Oral administration of nanoparticles is
      preferred but remains a challenge because transport across the intestinal
      epithelium is limited. We show that nanoparticles targeted to the neonatal Fc
      receptor (FcRn), which mediates the transport of immunoglobulin G antibodies
      across epithelial barriers, are efficiently transported across the intestinal
      epithelium using both in vitro and in vivo models. In mice, orally administered
      FcRn-targeted nanoparticles crossed the intestinal epithelium and reached
      systemic circulation with a mean absorption efficiency of 13.7%*hour compared
      with only 1.2%*hour for nontargeted nanoparticles. In addition, targeted
      nanoparticles containing insulin as a model nanoparticle-based therapy for
      diabetes were orally administered at a clinically relevant insulin dose of 1.1
      U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This
      effect was abolished in FcRn knockout mice, indicating that the enhanced
      nanoparticle transport was specifically due to FcRn. FcRn-targeted nanoparticles
      may have a major impact on the treatment of many diseases by enabling drugs
      currently limited by low bioavailability to be efficiently delivered though oral
      administration. 

PMID- 24285488
TI  - Effects of edge oxidation on the stability and half-metallicity of graphene
      quantum dots.
AB  - A comprehensive first-principles theoretical study of the electronic properties
      and half-metallic nature of zigzag edge-oxidized graphene quantum dots (GQDs) is
      carried out by using density functional theory (DFT) with the screened exchange
      hybrid functional of Heyd, Scuseria and Ernzerhof (HSE06). The oxidation schemes
      include -OH, -COOH and -COO groups. We identify oxidized GQDs whose opposite
      spins are localized at the two zigzag edges in an antiferromagnetic-type
      configuration, showing a spin-polarized ground state. Oxidized GQDs are more
      stable than the corresponding fully hydrogenated GQDs. The partially hydroxylated
      and carboxylated GQDs with the same size exhibit half-metallic state under almost
      the same electric-field intensity whereas fully oxidized GQDs behave as spin
      selective semiconductors. The electric-field intensity inducing the half metal
      increases with the length of the partially oxidized GQDs, ranging from M=4 to 7. 

PMID- 24285489
TI  - Investigation of an interleukin-6 receptor gene polymorphism (rs2228145) as a
      predictor of cardiovascular mortality in inflammatory polyarthritis: results from
      the Norfolk Arthritis Register.

PMID- 24285490
TI  - Hip replacement surgery in patients with ankylosing spondylitis.
AB  - OBJECTIVES: Although TNF-alpha inhibitors' striking effect on clinical symptoms
      have revolutionised the treatment of ankylosing spondylitis (AS), no certain
      influence on the development of spinal ankylosis and joint destruction has been
      documented. We wished to investigate whether improved treatment has affected the
      use of hip arthroplasty surgery. METHODS: Using the Norwegian Arthroplasty
      Register, we selected hip prosthesis procedures performed in patients with AS in
      1988-2010 (n=534), and compared the trend in the number of procedures being
      performed annually in 1988-2002 versus 2003-2010. Patients with osteoarthritis
      (OA) (n=95094) were used as a control group. RESULTS: The frequency of hip
      prosthesis surgery increased significantly in both groups up until 2002. In 2003
      2010, although not statistically significant (p=0.087), there was a trend towards
      a reduced frequency in the AS group when compared with the expected continued
      increase as was seen among patients with OA. Mean age at surgery increased
      significantly (p<0.001) from 49.9 years to 56.4 years when comparing patients
      with AS up until and after 2002. CONCLUSIONS: TNF-alpha inhibitors were
      introduced to patients with AS in Norway in 2000-2003, and our findings suggest
      that they may have altered the prognosis by inhibiting or slowing large joint
      arthritis and thus reducing the need for hip replacement surgery.

PMID- 24285491
TI  - Four-month metacarpal bone mineral density loss predicts radiological joint
      damage progression after 1 year in patients with early rheumatoid arthritis:
      exploratory analyses from the IMPROVED study.
AB  - AIM: To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal
      bone mineral density (BMD) loss after 4 months predicts radiological progression
      after 1 year of antirheumatic treatment. METHODS: Metacarpal BMD was measured 4
      monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in
      patients participating in the IMPROVED study, a clinical trial in 610 patients
      with recent onset RA (2010 criteria) or undifferentiated arthritis, treated
      according to a remission (disease activity score<1.6) steered strategy. With
      Sharp/van der Heijde progression >=0.5 points after 1 year (yes/no) as dependent
      variable, univariate and multivariate logistic regression analyses were
      performed. RESULTS: Of 428 patients with DXR-BMD results and progression scores
      available, 28 (7%) had radiological progression after 1 year. Independent
      predictors for radiological progression were presence of baseline erosions (OR
      (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)).
      In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only
      independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). CONCLUSIONS:
      In early RA patients, metacarpal BMD loss after 4 months of treatment is an
      independent predictor of radiological progression after 1 year. In patients
      without baseline erosions, early metacarpal BMD loss is the main predictor of
      radiological progression.

PMID- 24285492
TI  - Free fatty acids: potential proinflammatory mediators in rheumatic diseases.
AB  - OBJECTIVES: Due to their role in inflammatory metabolic diseases, we hypothesised
      that free fatty acids (FFA) are also involved in inflammatory joint diseases. To
      test this hypothesis, we analysed the effect of FFA on synovial fibroblasts (SF),
      human chondrocytes and endothelial cells. We also investigated whether the toll
      like receptor 4 (TLR4), which can contribute to driving arthritis, is involved in
      FFA signalling. METHODS: Rheumatoid arthritis SF, osteoarthritis SF, psoriatic
      arthritis SF, human chondrocytes and endothelial cells were stimulated in vitro
      with different FFA. Immunoassays were used to quantify FFA-induced protein
      secretion. TLR4 signalling was inhibited extracellularly and intracellularly.
      Fatty acid translocase (CD36), responsible for transporting long-chain FFA into
      the cell, was also inhibited. RESULTS: In rheumatoid arthritis synovial
      fibroblasts (RASF), FFA dose-dependently enhanced the secretion of the
      proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, as well as the
      matrix-degrading enzymes pro-MMP1 and MMP3. The intensity of the response was
      mainly dependent on the patient rather than on the type of disease. Both
      saturated and unsaturated FFA showed similar effects on RASF, while responses to
      the different FFA varied for human chondrocytes and endothelial cells.
      Extracellular and intracellular TLR4 inhibition as well as fatty acid transport
      inhibition blocked the palmitic acid-induced IL-6 secretion of RASF. CONCLUSIONS:
      The data show that FFA are not only metabolic substrates but may also directly
      contribute to articular inflammation and degradation in inflammatory joint
      diseases. Moreover, the data suggest that, in RASF, FFA exert their effects via
      TLR4 and require extracellular and intracellular access to the TLR4 receptor
      complex.

PMID- 24285493
TI  - Time trends in disease activity, response and remission rates in rheumatoid
      arthritis during the past decade: results from the NOR-DMARD study 2000-2010.
AB  - OBJECTIVES: To investigate whether baseline disease activity levels and responses
      in patients with rheumatoid arthritis (RA) changed during the period 2000-2010.
      METHODS: Data were provided by the Norwegian disease-modifying antirheumatic drug
      (NOR-DMARD) study. Patients with inflammatory joint diseases starting new
      treatment with disease-modifying antirheumatic drugs (DMARDs) were consecutively
      included and followed longitudinally. Time trend analyses were performed in
      methotrexate (MTX)-naive RA patients starting MTX monotherapy (MTX mono) and
      biologic DMARD (bDMARD)-naive RA patients starting tumour necrosis factor
      inhibitors+MTX (TNFi+MTX). RESULTS: A total of 2573 patients were included in the
      analyses: MTX mono n=1866 (69.9% female, 62.0% RF+, mean (SD) age 56.0 (13.7)
      years, median (25-75 percentile) time from diagnosis 0.2 (0.01-2.8) years);
      TNFi+MTX n=707 (70.3% female, 75.0% RF+, mean (SD) age 52.1 (13.2) years, median
      (25-75 percentile) time from diagnosis 5.7 (2.0-13.7) years). Significant time
      trends towards lower baseline disease activity score 28 (DAS28) as well as other
      disease activity measures were found in both groups (DAS28 from 5.17 to 4.75 in
      MTX mono and from 5.88 to 4.64 in TNFi+MTX), and disease duration became shorter.
      Six-month DAS28 remission rates increased significantly over the years (from 17.8
      to 37.6 in MTX mono and from 16.9 to 46.3 in TNFi+MTX). CONCLUSIONS: During the
      last decade, baseline RA disease activity level at the time of starting MTX as
      well as TNFi+MTX decreased from high to moderate. A more than twofold increase in
      6-month remission rates was observed in both groups. Our findings indicate that
      clinicians have implemented modern, more aggressive treatment strategies, which
      hopefully will lead to better long-term disease outcomes.

PMID- 24285494
TI  - The coupling of bone and cartilage turnover in osteoarthritis: opportunities for
      bone antiresorptives and anabolics as potential treatments?
AB  - Osteoarthritis (OA) is the most common form of arthritic disease, and a major
      cause of disability and impaired quality of life in the elderly. OA is a complex
      disease of the entire joint, affecting bone, cartilage and synovium that thereby
      presents multiple targets for treatment. This manuscript will summarise emerging
      observations from cell biology, preclinical and preliminary clinical trials that
      elucidate interactions between the bone and cartilage components in particular.
      Bone and cartilage health are tightly associated. Ample evidence has been found
      for bone changes during progression of OA including, but not limited to,
      increased turnover in the subchondral bone, undermineralisation of the trabecular
      structure, osteophyte formation, bone marrow lesions and sclerosis of the
      subchondral plate. Meanwhile, a range of investigations has shown positive
      effects on cartilage health when bone resorption is suppressed, or deterioration
      of the cartilage when resorption is increased. Known bone therapies, namely
      oestrogens, selective oestrogen receptor modifiers (SERMs), bisphosphonates,
      strontium ranelate, calcitonin and parathyroid hormone, might prove useful for
      treating two critical tissue components of the OA joint, the bone and the
      cartilage. An optimal treatment for OA likely targets at least these two tissue
      components. The patient subgroups for whom these therapies are most appropriate
      have yet to be fully defined but would likely include, at a minimum, those with
      high bone turnover. 

PMID- 24285496
TI  - Contactless conductivity detector array for capillary electrophoresis.
AB  - A CE system featuring an array of 16 contactless conductivity detectors was
      constructed. The detectors were arranged along 70 cm length of a capillary with
      100 cm total length and allow the monitoring of separation processes. As the
      detectors cannot be accommodated on a conventional commercial instrument, a
      purpose built set-up employing a sequential injection manifold had to be employed
      for automation of the fluid handling. Conductivity measurements can be considered
      universal for electrophoresis and thus any changes in ionic composition can be
      monitored. The progress of the separation of Na(+) and K(+) is demonstrated. The
      potential of the system to the study of processes in CZE is shown in two
      examples. The first demonstrates the differences in the developments of peaks
      originating from a sample plug with a purely aqueous background to that of a plug
      containing the analyte ions in the buffer. The second example visualizes the
      opposite migration of cations and anions from a sample plug that had been placed
      in the middle of the capillary. 

PMID- 24285495
TI  - Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison
      of adalimumab, etanercept and infliximab.
AB  - OBJECTIVE: To compare drug survival on adalimumab, etanercept and infliximab in
      patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=9139; 76%
      women; mean age 56 years) starting their first tumour necrosis factor (TNF)
      inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register
      (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5
      years of follow-up was compared overall and by period of treatment start (2003
      2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period,
      health assessment questionnaire (HAQ), disease duration, concomitant disease
      modifying antirheumatic drug (DMARD) treatment and general frailty (using
      hospitalisation history as proxy). RESULTS: During 20 198 person-years
      (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first
      biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse
      events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to
      1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI
      1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab
      (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but
      were modified by time for adalimumab versus etanercept (p<0.001; between-drug
      difference highest the 1st year in both periods). The discontinuation rate was
      higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to
      1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs
      2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased
      from 43% to 53% (p<0.001). CONCLUSIONS: Discontinuation rates were higher for
      infliximab compared with adalimumab and etanercept initiators, and for adalimumab
      versus etanercept during the 1st year. Discontinuation rates increased with
      calendar period, as did the percentage discontinuations due to inefficacy.

PMID- 24285497
TI  - Purinergic and muscarinic modulation of ATP release from the urothelium and its
      paracrine actions.
AB  - The urothelium is a newly recognized sensory structure that detects bladder
      fullness. Pivotal to this sensory role is the release of ATP from the urothelium.
      However, the routes for urothelial ATP release, its modulation by receptor
      mediated pathways, and the autocrine/paracrine role of ATP are poorly understood,
      especially in native tissue. We examined the action of key neurotransmitters:
      purinergic and muscarinic agonists on ATP release and its paracrine effect.
      Guinea pig and human urothelial mucosa were mounted in a perfusion trough;
      superfusate ATP was measured using a luciferin-luciferase assay, and tissue
      contractions were recorded with a tension transducer. Intracellular Ca2+ was
      measured in isolated urothelial cells with fura-2. The P2Y agonist UTP but not
      the P2X agonist alpha,beta-methylene-ATP generated ATP release. The muscarinic
      agonist carbachol and the M2-preferential agonist oxotremorine also generated ATP
      release, which was antagonized by the M2-specific agent methoctramine. Agonist
      evoked ATP release was accompanied by mucosal contractions. Urothelial ATP
      release was differentially mediated by intracellular Ca2+ release, cAMP,
      exocytosis, or connexins. Urothelium-attached smooth muscle exhibited spontaneous
      contractions that were augmented by subthreshold concentrations of carbachol,
      which had little direct effect on smooth muscle. This activity was attenuated by
      desensitizing P2X receptors on smooth muscle. Urothelial ATP release was
      increased in aging bladders. Purinergic and muscarinic agents produced similar
      effects in human urothelial tissue. This is the first demonstration of specific
      modulation of urothelial ATP release in native tissue by purinergic and
      muscarinic neurotransmitters via distinct mechanisms. Released ATP produces
      paracrine effects on underlying tissues. This process is altered during aging and
      has relevance to human bladder pathologies.

PMID- 24285498
TI  - Control of renin secretion from kidneys with renin cell hyperplasia.
AB  - In states of loss-of-function mutations of the renin-angiotensin-aldosterone
      system, kidneys develop a strong hyperplasia of renin-producing cells. Those
      additional renin cells are located outside the classic juxtaglomerular areas,
      mainly in the walls of preglomerular vessels and most prominently in multilayers
      surrounding afferent arterioles. Since the functional behavior of those ectopic
      renin cells is yet unknown, we aimed to characterize the control of renin
      secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys
      from mice lacking aldosterone synthase (AS-/- mice), which displayed 10-fold
      elevations of renin mRNA and plasma renin concentrations. On the absolute level,
      renin secretion from isolated AS-/- kidneys was more than 10-fold increased over
      wild-type kidneys. On the relative level, the stimulation of renin secretion by
      the beta-adrenergic activator isoproterenol or by lowering of the concentration
      of extracellular Ca2+ was very similar between the two genotypes. In addition,
      the inhibitory effects of ANG II and of perfusion pressure were similar between
      the two genotypes. Deletion of connexin40 blunted the pressure dependency of
      renin secretion and the stimulatory effect of low extracellular Ca2+ on renin
      secretion in the same manner in kidneys of AS-/- mice as in wild-type mice. Our
      findings suggest a high degree of functional similarity between renin cells
      originating during development and located at different positions in the adult
      kidney. They also suggest a high similarity in the expression of membrane
      proteins relevant for the control of renin secretion, such as beta1-adrenergic
      receptors, ANG II type 1 receptors, and connexin40.

PMID- 24285499
TI  - Inflammasomes are important mediators of cyclophosphamide-induced bladder
      inflammation.
AB  - Bladder inflammation (cystitis) underlies numerous bladder pathologies and is
      elicited by a plethora of agents such as urinary tract infections, bladder outlet
      obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll
      like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen-
      and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively)
      are key components of the innate immune system that coordinates the production
      (TLRs) and maturation (NLRs) of proinflammatory IL-1beta. Despite multiple
      studies of TLRs in the bladder, none have investigated NLRs beyond one small
      survey. We now demonstrate that NLRP3 and NLRC4, and their binding partners
      apoptosis-associated speck-like protein containing a COOH-terminal caspase
      recruitment domain (ASC) and NLR family apoptosis inhibitory protein (NAIP), are
      expressed in the bladder and localized predominantly to the urothelia. Activated
      NLRs form inflammasomes that activate caspase-1. Placement of a NLRP3- or NLRC4
      activating PAMP or NLRP3-activating DAMPs into the lumen of the bladder
      stimulated caspase-1 activity. To investigate inflammasomes in vivo, we induced
      cystitis with cyclophosphamide (CP, 150 mg/kg ip) in the presence or absence of
      the inflammasome inhibitor glyburide. Glyburide completely blocked CP-induced
      activation of caspase-1 and the production of IL-1beta at 4 h. At 24 h, glyburide
      reduced two markers of inflammation by 30-50% and reversed much of the
      inflammatory morphology. Furthermore, glyburide reversed changes in bladder
      physiology (cystometry) induced by CP. In conclusion, NLRs/inflammasomes are
      present in the bladder urothelia and respond to DAMPs and PAMPs, whereas NLRP3
      inhibition blocks bladder dysfunction in the CP model. The coordinated response
      of NLRs and TLRs in the urothelia represents a first-line innate defense that may
      provide an important target for pharmacological intervention. 

PMID- 24285501
TI  - Basic fibroblast growth factor reduces functional and structural damage in
      chronic kidney disease.
AB  - Chronic kidney disease (CKD) is characterized by loss of renal function. The
      pathological processes involved in the progression of this condition are already
      known, but the molecular mechanisms have not been completely explained. Recent
      reports have shown the intrinsic capacity of the kidney to undergo repair after
      acute injury through the reexpression of repairing proteins (Villanueva S,
      Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006).
      Stimulation with basic fibroblast growth factor (bFGF) could accelerate this
      process. However, it is not known whether bFGF can induce this phenomenon in
      kidney cells affected by CKD. Our aim was to study the evolution of renal damage
      in animals with CKD treated with bFGF and to relate the amount of repairing
      proteins with renal damage progression. Male Sprague-Dawley rats were subjected
      to 5/6 nephrectomy (NPX) and treated with bFGF (30 MUg/kg, NPX+bFGF); a control
      NPX group was treated with saline (NPX+S). Animals were euthanized 35 days after
      bFGF administration. Functional effects were assessed based on serum creatinine
      levels; morphological damage was assessed by the presence of macrophages (ED-1),
      interstitial alpha-smooth muscle actin (alpha-SMA), and interstitial collagen
      through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the
      epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin,
      Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4.
      We observed a significant reduction in serum creatinine levels, ED-1, alpha-SMA,
      and Sirius red as well as an important induction of Oct-4, angiogenic factors,
      and repairing proteins in NPX+bFGF animals compared with NPX+S animals. These
      results open new perspectives toward reducing damage progression in CKD.

PMID- 24285500
TI  - Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II
      induced hypertensive mice.
AB  - NAD(P)H oxidase (Nox)2 and Nox4 are the isoforms of Nox expressed in the macula
      densa (MD). MD-derived superoxide (O2-), primarily generated by Nox2, is enhanced
      by acute ANG II stimulation. However, the effects of chronic elevations in ANG II
      during ANG II-induced hypertension on MD-derived O2- are unknown. We infused a
      slow pressor dose of ANG II (600 ng.min-1.kg-1) for 2 wk in C57BL/6 mice and
      found that mean arterial pressure was elevated by 22.3 +/- 3.4 mmHg (P < 0.01).
      We measured O2- generation in isolated and perfused MDs and found that O2-
      generation by the MD was increased from 9.4 +/- 0.9 U/min in control mice to 34.7
      +/- 1.8 U/min in ANG II-induced hypertensive mice (P < 0.01). We stimulated MMDD1
      cells, a MD-like cell line, with ANG II and found that O2- generation increased
      from 921 +/- 91 to 3,687 +/- 183 U.min-1.105 cells-1, which was inhibited with
      apocynin, oxypurinol, or NS-398 by 46%, 14%, and 12%, respectively. We isolated
      MD cells using laser capture microdissection and measured mRNA levels of Nox.
      Nox2 and Nox4 levels increased by 3.7 +/- 0.17- and 2.6 +/- 0.15-fold in ANG II
      infused mice compared with control mice. In MMDD1 cells treated with Nox2 or Nox4
      small interfering (si)RNAs, ANG II-stimulated O2- generation was blunted by 50%
      and 41%, respectively. In cells treated with p22(phox) siRNA, ANG II-stimulated
      O2- generation was completely blocked. In conclusion, we found that a subpressor
      dose of ANG II enhances O2- generation in the MD and that the sources of this O2-
      are primarily Nox2 and Nox4.

PMID- 24285502
TI  - Risk of acute myocardial infarction, stroke, or death in patients initiating
      olmesartan or other angiotensin receptor blockers - a cohort study using the
      Clinical Practice Research Datalink.
AB  - PURPOSE: Results of two randomized trials (ROADMAP and ORIENT) suggest that high
      dose (40 mg/day) olmesartan (Olm) is associated with increased cardiovascular
      mortality compared to placebo in diabetic patients. We evaluated the risks of
      acute myocardial infarction (AMI) and death in patients initiating Olm compared
      with an active comparator group, other angiotensin receptor blockers (ARBs), with
      a focus on high-dose and diabetic subgroups. METHODS: We conducted a cohort study
      with patients who initiated Olm or another ARB between 2003 and 2011, using the
      UK Clinical Practice Research Datalink GOLD. We included patients who had no
      prior ARB or angiotensin converting enzyme inhibitor exposure during the
      preceding 6 months. Hazard ratios (HRs) were estimated using Cox regression
      models with both multivariable adjustment and propensity score matching. RESULTS:
      There were 3964 Olm and 54 653 other-ARB initiators, respectively. Adjusted HRs
      comparing Olm and other-ARBs were 1.04 (95% CI: 0.75-1.42) for AMI and 1.16 (0.95
      1.42) for death, using multivariable adjustment. Comparing patients initiated
      with a high-dose Olm and a high-dose other-ARB, HRs were 3.09 (0.94-10.13) for
      AMI and 2.03 (0.74-5.61) for death, using multivariable adjustment; and 4.38
      (0.97-19.66) and 1.99 (0.63-6.32) for AMI and death, using propensity score
      matching. CONCLUSIONS: Overall, no differences in risk were observed in the main
      cohort analyses comparing Olm initiators with patients initiating therapy with
      other ARBs; however, HRs were marginally increased for all study endpoints which
      compared high-dose subgroups, suggesting potential increased risk may be
      associated with high-dose Olm. Published 2013. This article is a U.S. Government
      work and is in the public domain in the USA.

PMID- 24285503
TI  - Multi-arm PEG/silica hydrogel for sustained ocular drug delivery.
AB  - In the present study, a series of sustained drug delivery multiarm poly(ethylene
      glycol) (PEG)/silica hydrogels were prepared and characterized. The hydrogels
      were formed by hydrolysis and condensation of poly(4-arm PEG silicate) using the
      sol-gel method. The relationships between water content in the PEG/silica
      hydrogel and stability as well as rheological properties were evaluated. Scanning
      electron microscopy analysis of the PEG/silica hydrogels revealed water content
      dependent changes in microstructure. An increase in water content resulted in
      larger pores within the hydrogel, longer gelation time and higher viscosity. The
      PEG/silica hydrogels were loaded with dexamethasone (DMS) or dexamethasone sodium
      phosphate (DMSP), drugs that are hydrophobic and hydrophilic in nature,
      respectively. Evaluation of in vitro release revealed a zero-order release
      profile for DMS over the first 6 days, suggesting that degradation of the silica
      hydrogel matrix was the primary mechanism of drug release. It was also found that
      the drug-release profile could be tailored by varying the water content used
      during hydrogel preparation. In contrast, more than 90% of DMSP was released
      within 1 h, suggesting that DMSP release was only controlled by diffusion.
      Overall, results from this study indicate that PEG/silica hydrogels may be
      promising drug-eluting depot materials for the sustained delivery of hydrophobic,
      ophthalmic drugs.

PMID- 24285504
TI  - Does omega-3 fatty acid supplementation enhance neural efficiency? A review of
      the literature.
AB  - OBJECTIVE: While the cardiovascular, anti-inflammatory and mood benefits of omega
      3 supplementation containing long chain fatty acids (LCPUFAs) such as
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are manifest, there is
      no scientific consensus regarding their effects on neurocognitive functioning.
      This review aimed to examine the current literature on LCPUFAs by assessing their
      effects on cognition, neural functioning and metabolic activity. In order to view
      these findings together, the principle of neural efficiency as established by
      Richard Haier ("smart brains work less hard") was extended to apply to the
      neurocognitive effects of omega-3 supplementation. METHODS: We reviewed multiple
      databases from 2000 up till 2013 using a systematic approach and focused our
      search to papers employing both neurophysiological techniques and cognitive
      measures. RESULTS: Eight studies satisfied the criteria for consideration. We
      established that studies using brain imaging techniques show consistent changes
      in neurochemical substances, brain electrical activity, cerebral metabolic
      activity and brain oxygenation following omega-3 supplementation. CONCLUSIONS: We
      conclude that, where comparison is available, an increase in EPA intake is more
      advantageous than DHA in reducing "brain effort" relative to cognitive
      performance.

PMID- 24285505
TI  - Controllable shrinking of inverted-pyramid silicon nanopore arrays by dry-oxygen
      oxidation.
AB  - A novel and simple technique for the controllable shrinkage of inverted-pyramid
      silicon (Si) nanopore arrays is reported. The Si nanopore arrays with sizes from
      60 to 150 nm, made using a combination of dry and wet etching, were shrunk to sub
      10 nm, or even closed, using direct dry-oxygen oxidation at 900  degrees  C. The
      shrinkage process of the pyramidal nanopore induced by oxidation was carefully
      modeled and simulated. The simulation was found to be in good agreement with the
      experimental data within most of the oxidation time range. Using this method,
      square nanopore arrays with an average size of 30 nm, and rectangular nanopores
      and nanoslits with feature sizes as small as 8 nm, have been obtained.
      Furthermore, focused ion beam cutting experiments revealed that the inner
      structure of the nanopore after the shrinkage kept its typical inverted-pyramid
      shape, which is of importance in many fields such as biomolecular sensors and
      ionic analogs of electronic devices, as well as nanostencils for surface nano
      patterning.

PMID- 24285506
TI  - Ionic-liquid-mediated poly(dimethylsiloxane)- grafted carbon nanotube fiber
      prepared by the sol-gel technique for the head space solid-phase microextraction
      of methyl tert-butyl ether using GC.
AB  - A headspace solid-phase microextraction method was developed for the
      preconcentration and extraction of methyl tert-butyl ether. An ionic-liquid
      mediated multiwalled carbon nanotube-poly(dimethylsiloxane) hybrid coating, which
      was prepared by covalent functionalization of multiwalled carbon nanotubes with
      hydroxyl-terminated poly(dimethylsiloxane) using the sol-gel technique, was used
      as solid-phase microextraction adsorbent. This innovative fiber exhibited a
      highly porous surface structure, high thermal stability (at least 320 degrees C)
      and long lifespan (over 210 uses). Potential factors affecting the extraction
      efficiency were optimized. Under the optimum conditions, the method LOD (S/N = 3)
      was 0.007 ng/mL and the LOQ (S/N = 10) was 0.03 ng/mL. The calibration curve was
      linear in the range of 0.03-200 ng/mL. The RSDs for one fiber (repeatability, n =
      5) at three different concentrations (0.05, 1, and 150 ng/mL) were 5.1, 4.2, and
      4.6% and for the fibers obtained from different batches (reproducibility, n = 3)
      were 6.5, 5.9, and 6.3%, respectively. The developed method was successfully
      applied to the determination of methyl tert-butyl ether in different real water
      samples on three consecutive days. The relative recoveries for the spiked samples
      with 0.05, 1, and 150 ng/mL were between 94-104%. 

PMID- 24285507
TI  - Simultaneous and rapid determination of caffeine and taurine in energy drinks by
      MEKC in a short capillary with dual contactless conductivity/photometry
      detection.
AB  - A method has been developed for the simultaneous determination of taurine and
      caffeine using a laboratory-made instrument enabling separation analysis in a
      short 10.5 cm capillary. The substances are detected using a contactless
      conductometry/ultraviolet (UV) photometry detector that enables recording both
      signals at one place in the capillary. The separation of caffeine and taurine was
      performed using the MEKC technique in a BGE with the composition 40 mM CHES, 15
      mM NaOH, and 50 mM SDS, pH 9.36. Under these conditions, the migration time of
      caffeine is 43 s and of taurine 60 s; LOD for caffeine is 4 mg/L using
      photometric detection and LOD for taurine is 24 mg/L using contactless
      conductometric detection. The standard addition method was used for determination
      in Red Bull energy drink of caffeine 317 mg/L and taurine 3860 mg/L; the contents
      in Kamikaze drink were 468 mg/L caffeine and 4110 mg/L taurine. The determined
      values are in good agreement with the declared contents of these substances. RSD
      does not exceed 3%. 

PMID- 24285509
TI  - Poly(ethylene glycol) stabilized mesoporous metal-organic framework nanocrystals:
      efficient and durable catalysts for the oxidation of benzyl alcohol.
AB  - Active, selective, and stable: The fabrication of uniform mesoporous Cu3(BTC)2
      (BTC: 1,3,5-benzenetricarboxylate) nanocrystals with tunable size and porosity is
      reported. The as-synthesized Cu3(BTC)2 structures show high activity,
      selectivity, and stability for the aerobic oxidation of benzyl alcohol to
      aldehyde.

PMID- 24285508
TI  - Support needs and resources of sexual minority women with breast cancer.
AB  - OBJECTIVE: The current paper utilizes qualitative methods to better understand
      the support needs and resources of sexual minority women (SMW) breast cancer
      patients. METHODS: Thirteen semi-structured interviews were conducted with SMW,
      who were recruited from community-based organizations and had undergone
      mastectomy for treatment of breast cancer. Interviews explored support needs and
      resources. Data were analyzed using thematic analysis. RESULTS: Three key domains
      emerged: support groups, family of origin support, and partner support.
      Participants emphasized the value of cancer support groups and resources tailored
      to SMW while stating that other dimensions of identity or experience,
      particularly age and cancer stage, were also important. Participants noted the
      dearth of social support resources for same-sex partners. Family of origin and
      partners were typically participants' primary sources of tangible and emotional
      support; participants often engaged in protective buffering to mitigate
      caregivers' distress. Single women faced the greatest challenges in terms of
      support needs and resources. Former partners were often key sources of support.
      CONCLUSIONS: SMW and their partners have many shared and unique support resources
      and barriers. Heteronormativity that is implicit in the structure of support
      resources can serve as a barrier to support for SMW and their partners.
      Flexibility in relationship roles enabling some SMW to include former partners as
      significant means of support may be a source of resiliency, particularly for
      unpartnered SMW cancer patients. Support needs and resources of SMW are best
      understood through an intersectionality framework that considers sexual
      orientation, relationship status, cancer stage, age, healthcare access, and other
      important identities and experiences.

PMID- 24285510
TI  - Pharmacokinetics of Peptide-Fc fusion proteins.
AB  - Peptide-Fc fusion proteins (or peptibodies) are chimeric proteins generated by
      fusing a biologically active peptide with the Fc-domain of immunoglobulin G. In
      this review, we describe recent studies that have evaluated the absorption,
      distribution, metabolism, and excretion characteristics of peptibodies. Key
      features of the pharmacokinetics of peptibodies include their extended half-life
      due to recycling by the neonatal Fc receptor (FcRn), a substantial contribution
      by renal excretion to total clearance and, for certain peptibodies, target
      mediated drug disposition. The prolonged half-life of peptibodies permits less
      frequent dose administration compared with small therapeutic peptides, thereby
      supporting patient convenience and compliance. Hence, a considerable number of
      peptibodies are currently in preclinical and clinical development. Investigation
      of the metabolism (biotransformation) of biologics is an evolving area of
      research: ligand-binding mass spectrometry techniques have been employed for the
      characterization of the peptibody romiplostim, providing a new approach to
      evaluation of the degradation products of biologics.
      Pharmacokinetic/pharmacodynamic modeling and simulation techniques have been used
      to predict the pharmacokinetics of peptibodies which can inform clinical decision
      making, particularly selection of dosing regimens. This integrated review
      highlights the distinct pharmacokinetic characteristics of peptibodies and their
      influence on the drug development process for this emerging family of
      therapeutics.

PMID- 24285511
TI  - 11th International Isotope Symposium on the Synthesis and Applications of
      Isotopes and Isotopically Labelled Compounds (IIS2012).

PMID- 24285513
TI  - Selected scientific topics of the 11th International Isotope Symposium on the
      Synthesis and Applications of Isotopes and Isotopically Labeled Compounds.
AB  - This micro-review describes hot topics and new trends in isotope science
      discussed at the 11th International Isotope Symposium on the Synthesis and
      Applications of Isotopes and Isotopically Labeled Compounds from a personal
      perspective.

PMID- 24285514
TI  - Melvin Calvin award lecture, Isotopic chemistry: the most varied of
      careers...with tritium and deuterium the most versatile of the isotopes.
AB  - Isotopic chemistry offers the opportunity for organic chemists to explore a
      surprisingly large variety of scientific avenues. It lends itself naturally to
      multidisciplinary research projects and provides the sophisticated tools with
      which the most complex of processes can be investigated. This Melvin Calvin Award
      lecture will keep to a broadly chronological theme and will give examples of how
      the remarkable versatility of the two heavy hydrogen isotopes has been utilised
      during collaborative studies in areas as varied as plant and insect biochemistry,
      drug metabolism and pharmacokinetics, structure determination, NMR spectroscopy,
      reaction mechanisms, molecular energetics and novel catalyst development. Few
      other careers can provide the opportunity to study such varied and fundamental
      subjects and still provide challenges that are as compelling and exciting some 4
      decades later. 

PMID- 24285516
TI  - (18) F-labeled folic acid derivatives for imaging of the folate receptor via
      positron emission tomography.
AB  - The folate receptor (FR) is already known as a proven target in diagnostics and
      therapy of cancer. Furthermore, the FR is involved in inflammatory and autoimmune
      diseases. The major advantage as a valuable target is its strongly limited
      expression in healthy tissues. Over the past two decades, several folic acid
      based radiopharmaceuticals addressing the FR have been developed, and some of
      them show great potential for applications in clinical routine. However, most of
      these radiofolates were developed for single photon emission computed tomography
      imaging, and only a few can be used for positron emission tomography (PET)
      imaging. The development of suitable (18) F-labeled derivatives for PET imaging
      of the FR has aroused great interest and recent studies revealed very promising
      candidates for further development and translation into human applications. In
      this review, we focus on the development of (18) F-labeled folic acid derivatives
      for PET imaging of the FR and discuss various radiochemical strategies and
      approaches towards (18) F-folates. Besides radiochemistry and (18) F-labeling, we
      briefly look into the crucial pharmacological parameters and the preclinical in
      vivo performance of those (18) F-folates.

PMID- 24285517
TI  - A perspective on tritium versus carbon-14: ensuring optimal label selection in
      pharmaceutical research and development.
AB  - Tritium ((3) H) and carbon-14 ((14) C) labels applied in pharmaceutical research
      and development each offer their own distinctive advantages and disadvantages
      coupled with benefits and risks. The advantages of (3) H have a higher specific
      activity, shorter half-life that allows more manageable waste remediation, lower
      material costs, and often more direct synthetic routes. The advantages of (14) C
      offer certain analytical benefits and less potential for label loss. Although (3)
      H labels offer several advantages, they might be overlooked as a viable option
      because of the concerns about its drawbacks. A main drawback often challenged is
      metabolic liability. These drawbacks, in some cases, might be overstated leading
      to underutilization of a perfectly viable option. As a consequence, label
      selection may automatically default to (14) C, which is a more conservative
      approach. To challenge this '(14) C-by-default' approach, pharmaceutical agents
      with strategically selected (3) H-labeling positions based on non-labeled
      metabolism data have been successfully implemented and evaluated for (3) H loss.
      From in-house results, the long term success of projects clearly would benefit
      from a thorough, objective, and balanced assessment regarding label selection
      ((3) H or (14) C). This assessment should be based on available project
      information and scientific knowledge. Important considerations are project
      applicability (preclinical and clinical phases), synthetic feasibility, costs,
      and timelines. 

PMID- 24285515
TI  - Kinetic deuterium isotope effects in cytochrome P450 oxidation reactions.
AB  - Cytochrome P450 (P450) enzymes account for ~75% of the metabolism of drugs. Most
      of the reactions catalyzed by P450s are mixed-function oxidations, and a C-H bond
      is (usually) broken. The rate-limiting nature of this step can be analyzed using
      the kinetic isotope effect (KIE) approach. The most relevant type of KIE is one
      termed intermolecular non-competitive, indicative of rate-limiting C-H bond
      breaking. A plot of KIE versus kcat for several P450s showed a correlation
      coefficient (r(2) ) of 0.62. Deuterium substitution has been considered as a
      potential means of slowing drug metabolism or redirecting sites of metabolism in
      some cases, and several general points can be made regarding the potential for
      application of deuterium in drug design/development based on what is known about
      P450 KIEs.

PMID- 24285518
TI  - Preparation of [(3) H]fluoroethyl tosylate and its use in the labelling of the
      dopamine transporter radioligand [(3) H]FE-PE2I.
AB  - [(3) H]Fluoroethyl tosylate, a novel alkylating tritium labelling agent, was
      synthesized from tritium gas with high specific activity and with 99%
      radiochemical purity. [(3) H]Fluoroethyl tosylate was applied in the tritium
      labelling of the dopamine transporter radioligand [(3) H]FE-PE2I.

PMID- 24285519
TI  - Application of neutral iridium(I) N-heterocyclic carbene complexes in ortho
      directed hydrogen isotope exchange.
AB  - Bench-stable complexes of the type [Ir(COD)(NHC)Cl] (NHC = N-heterocyclic
      carbene) have been investigated within the field of hydrogen isotope exchange. By
      employing a sterically encumbered NHC within such complexes and catalyst loadings
      of only 5 mol%, moderate to high deuterium incorporations were achieved across a
      range of aromatic ketones and nitrogen-based heterocycles. The simple and
      synthetically accessible catalysts reported herein present alternatives to
      phosphine-based species and increase the available labelling systems with respect
      to established iridium-based isotope exchange methodologies. 

PMID- 24285520
TI  - Radiolabelling of steroids: the synthesis of 17alpha-[4-(14) C]trenbolone.
AB  - 17beta-Hydroxyestra-4,9,11-trien-3-one or trenbolone is an anabolic steroid used
      in some meat producing countries where its use is licenced. In cattle it is
      metabolised into 17alpha-trenbolone. We were required to make 17alpha-[4-(14)
      C]trenbolone for use in environmental fate studies. At the same time we also had
      a request to make 17alpha-[4-(14) C]estradiol so we combined the two syntheses
      and made use of the synergy to allow us to make a batch of 17alpha-[4-(14)
      C]estradiol by known methodology and then elaborate a portion of this into
      17alpha-[4-(14) C]trenbolone. The synthesis of 17alpha-[4-(14) C]trenbolone from
      17alpha-[4-(14) C]estradiol was achieved in 8 steps and 3.1% overall yield to
      give material with a radiochemical purity of 99.5% and specific activity of 59
      mCi/mmol. 

PMID- 24285521
TI  - Carbon-14 labeling of K777*HCl, a therapeutic agent for Chagas disease.
AB  - The antitrypanosomal agent K777*HCl was labeled with carbon-14 to support
      absorption, distribution, metabolism, and excretion studies of this potential new
      drug for the treatment of Chagas disease. The radiolabeled compound was prepared
      in eight steps from [(14) C(U)]-(l)-phenylalanine with a specific activity of
      54.4 mCi/mmol and an overall radiochemical yield of 4.1%. 

PMID- 24285522
TI  - Syntheses of C-13 and C-14-labeled versions of the investigational proteasome
      inhibitor MLN9708.
AB  - MLN9708 (ixazomib citrate) is an investigational, orally bioavailable proteasome
      inhibitor that is under development by Millennium in clinical studies in both
      hematologic and nonhematologic malignancies. The stable isotope-labeled MLN9708
      was required for bio-analytical studies. [(13) C9 ]-MLN9708 (11) was synthesized
      in seven steps from the uniformly labeled [(13) C6 ]-1,4-dichlorobenzene (3) and
      [1-(13) C]-acetyl chloride. Because of the presence of two chlorine atoms and a
      boron atom, compound 6 was further reacted with [(13) C2 ]-glycine to provide an
      internal standard that is well separated from the parent compound during mass
      spectrometric analysis. The radiolabeled version was prepared to support
      metabolite profiling and whole body autoradiography studies in experimental
      animals. [(14) C]-MLN9708 (19) was synthesized in six steps from commercially
      available [(14) C]-barium carbonate. The key intermediate, [carboxyl-(14) C]-2,5
      dichlorobenzoic acid (14), was prepared by selective lithiation of 1-bromo-2,5
      dichlorobenzene (12) followed by carbonation with [(14) C]-barium carbonate. In
      preparation for a one-time human absorption, distribution, metabolism and
      excretion (ADME) study, the stability of [(14) C]-MLN9708 and its precursors were
      also evaluated.

PMID- 24285523
TI  - Carbon-14 labelled tribendimidine, a broad-spectrum anthelmintic drug.
AB  - The preparation of [(14) C]tribendimidine, a broad-spectrum anthelmintic agent
      related to amidantel, and its use during excretion and metabolism studies in the
      rat are described in this paper. 

PMID- 24285524
TI  - Synthesis of isotopically labeled versions of L-MTP-PE (mifamurtide) and MDP.
AB  - L-MTP-PE (1), an immunomodulator and its metabolite MDP (4) were synthesized from
      labeled l-alanine and its protected derivative, respectively. The key
      intermediate product for the labeled L-MTP-PE synthesis, [(13) C3 ,D4 ]-alanyl
      cephalin (2A), was synthesized from [(13) C3 ,D4 ]-l-alanine (3A) in three steps.
      The key intermediate product for labeled MDP synthesis, amine 11, was prepared
      from [(13) C3 ,(15) N]-Boc-l-alanine (5A) in two steps. 

PMID- 24285525
TI  - Syntheses of (3) H-labeled, (14) C-labeled, and (2) H4 -labeled SCH 444877,
      phosphodiesterase type 5 inhibitors.
AB  - The syntheses of [(3) H]SCH 444877, [(2) H4 ]SCH 444877, and [(14) C]SCH 444877
      are described. [(3) H]SCH 444877 was prepared in three steps from tritium gas.
      [(2) H4 ]SCH 444877 was synthesized from [(2) H4 ]ethanolamine in four steps with
      an overall yield of 40%. [(14) C]SCH 444877 was prepared from barium [(14)
      C]cyanamide in 10 steps with an overall yield of 8.1%.

PMID- 24285526
TI  - A convergent stereocontrolled synthesis of [3-(14) C]solanesol.
AB  - In this communication, we report the synthesis of ~5 mCi of [3-(14) C]solanesol
      (1) prepared from ethyl [3-(14) C]acetoacetate and (all-E)-octaprenyl bromide (2)
      in four steps, with a specific radioactivity of 19.83 mCi/mmol and with a
      chemical/stereochemical and radiochemical purity of >= 95%. (Figure ). Position 3
      of the chain was selected for (14) C labelling because of the metabolic stability
      of this position. Unlabelled (all-E)-octaprenyl (18) (Scheme ) necessary for this
      work was prepared via a convergent iterative 'allyl-allyl' coupling approach of
      precursors easily derived from readily available inexpensive starting
      materials.(1)

PMID- 24285527
TI  - The synthesis of a carbon-14 labeled pegylated AdnectinTM for placental transfer
      studies in guinea pigs.
AB  - AdnectinsTM are novel fibronectin-based proteins containing domains engineered to
      bind to targets of therapeutic interest. The molecular weights of adnectins are
      less than conventional monoclonal antibodies but larger than traditional small
      molecules. Until now, there has been no information on the placental transfer of
      adnectins. To assess placental permeability to adnectins in pregnant guinea pigs,
      a radiolabeled adnectin, ATI-1072, bound to polyethylene glycol through a [(14)
      C]Maleimide linker, was synthesized from [1,4-(14) C]Maleic acid. This
      publication describes the synthesis and analysis of PEG-[(14) C]Maleimide
      adnectin ([(14) C]ATI-1072).

PMID- 24285528
TI  - Production of high specific activity (195m) Pt-cisplatinum at South African
      Nuclear Energy Corporation for Phase 0 clinical trials in healthy individual
      subjects.
AB  - Platinum agents continue to be the main chemotherapeutic agents used in the first
      line and second-line treatments of cancer patients. It is important to fully
      understand the biological profile of these compounds in order to optimize the
      dose given to each patient. In a joint project with the Australian Nuclear
      Science and Technology Organisation and the Nuclear Medicine Department at Steve
      Biko Academic Hospital, South African Nuclear Energy Corporation synthesized and
      supplied (195m) Pt-cisplatinum (commonly referred to as cisplatin) for a clinical
      pilot study on healthy volunteers. Enriched (194) PtCl2 was prepared by digestion
      of enriched (194) Pt metal (>95%) followed by thermal decomposition over a 3 h
      period. The (194) PtCl2 was then placed in a quartz ampoule, was irradiated in
      SAFARI-1 up to 200 h, then decay cooled for a minimum of 34 h prior to synthesis
      of final product. (195m) Pt(NH3 )2 I2 , formed with the addition of KI and NH4
      OH, was converted to the diaqua species [(195m) Pt(NH3 )2 (H2 O)2 ](2+) by
      reaction with AgNO3 . The conversion to (195m) Pt-cisplatinum was completed by
      the addition of concentrated HCl. The final product yield was 51.7% +/- 5.2% (n =
      5). The chemical and radionuclidic purity in each case was >95%. The use of a
      high flux reactor position affords a higher specific activity product (15.9 +/-
      2.5 MBq/mg at end of synthesis) than previously found (5 MBq/mg). Volunteers
      received between 108 and 126 MBq of radioactivity, which is equivalent to 6.8
      10.0 mg of carrier cisplatinum. Such high specific activities afforded a
      significant reduction (~50%) in the chemical dose of a carrier cisplatinum, which
      represents less than 10% of a typical chemotherapeutic dose given to patients. A
      good manufacturing practice GMP compliant product was produced and was
      administered to 10 healthy volunteers as part of an ethically approved Phase 0
      clinical trial. The majority of the injected activity 27.5% +/- 5.8% was excreted
      in the urine within 5 h post injection (p.i.). Only 8.5% +/- 3.1% of cisplatinum
      remained in blood pools at 5 h, which gradually cleared over the 6-day monitoring
      period p.i. At the end of the study (6 days p.i.), a total of 37.4% +/- 5.3% of
      the product had cleared from the blood into urine, and approximately 63% remained
      in the body. The significantly lower concentration of carrier cisplatinum used
      for imaging resulted in a well-tolerated product.

PMID- 24285529
TI  - Effect of deuteration on the metabolism and clearance of some pharmacologically
      active compounds--synthesis and in vitro metabolism of deuterated derivatives of
      dronedadrone.
AB  - The synthesis and in vitro metabolism studies of a family of specifically
      deuterated derivatives of dronedarone are described. Metabolic stability and
      clearance of the parent compound are not sensitive to deuterium substitution,
      irrespective of the position of the heavy label. 

PMID- 24285530
TI  - Preparation of labeled human drug metabolites and drug-drug interaction-probes
      with fungal peroxygenases.
AB  - Enzymatic conversion of a drug can be an efficient alternative for the
      preparation of a complex metabolite compared with a multi-step chemical synthesis
      approach. Limitations exist for chemical methods for direct oxygen incorporation
      into organic molecules often suffering from low yields and unspecific oxidation
      and also for alternative whole-cell biotransformation processes, which require
      specific fermentation know-how. Stable oxygen-transferring biocatalysts such as
      unspecific peroxygenases (UPOs) could be an alternative for the synthesis of
      human drug metabolites and related stable isotope-labeled analogues. This work
      shows that UPOs can be used in combination with hydrogen/deuterium exchange for
      an efficient one-step process for the preparation of 4'-OH-diclofenac-d6. The
      scope of the reaction was investigated by screening of different peroxygenase
      subtypes for the transformation of selected deuterium-labeled substrates such as
      phenacetin-d3 or lidocaine-d3. Experiments with diclofenac-d7 revealed that the
      deuterium-labeling does not affect the kinetic parameters. By using the latter
      substrate and H2 (18) O2 as cosubstrate, it was possible to prepare a doubly
      isotope-labeled metabolite (4'-(18) OH-diclofenac-d6). UPOs offer certain
      practical advantages compared with P450 enzyme systems in terms of stability and
      ease of handling. Given these advantages, future work will expand the existing
      'monooxygenation toolbox' of different fungal peroxygenases that mimic P450 in
      vitro reactions.

PMID- 24285531
TI  - Synthesis of deuterated [D32 ]oleic acid and its phospholipid derivative [D64
      ]dioleoyl-sn-glycero-3-phosphocholine.
AB  - Oleic acid and its phospholipid derivatives are fundamental to the structure and
      function of cellular membranes. As a result, there has been increasing interest
      in the availability of their deuterated forms for many nuclear magnetic
      resonance, infrared, mass spectroscopy and neutron scattering studies. Here, we
      present for the first time a straightforward, large-scale (gram quantities)
      synthesis of highly deuterated [D32 ]oleic acid by using multiple, yet simple and
      high yielding reactions. The precursors for the synthesis of [D32 ]oleic acid are
      [D14 ]azelaic acid and [D17 ]nonanoic acid, which were obtained by complete
      deuteration (>98% D) of their (1) H forms by using metal catalysed hydrothermal
      H/D exchange reactions. The oleic acid was produced with ca. 94% D isotopic
      purity and with no contamination by the trans-isomer (elaidic acid). The
      subsequent synthesis of [D64 ]dioleoyl-sn-glycero-3-phosphocholine from [D32
      ]oleic acid is also described.

PMID- 24285532
TI  - Biodistribution (as determined by the radiolabelled equivalent) of a gold(III)
      bis(pyrrolide-imine) Schiff base complex: a potential chemotherapeutic.
AB  - The biodistribution of an N2 N2 ' tetradentate gold(III) chelate, which is known
      to be cytotoxic towards a range of human cancer cell lines, was determined by a
      radiolabelled equivalent of the compound. The (198) Au-labelled gold(III) chelate
      of a bis(pyrrolide-imine) Schiff base ligand with a three-carbon di(azomethine)
      linkage was successfully synthesised with a high radiochemical yield of 73% and
      radiochemical purity of >95%. The high energy gamma-ray emitted by the (198) Au
      nucleus was used to follow the biodistribution of the compound in vivo in six
      male Sprague Dawley rats on a gamma camera. The log Po/w value of the (nat) Au
      analogue, -1.92(2), showed that the compound is hydrophilic and therefore likely
      to largely remain in the blood pool. This was confirmed by the biodistribution
      study, which showed 21% of the injected dose (ID) remained in the blood pool 4.5
      h after injection. This decreased to 10.8% over a 24-h period. The activity
      measured in the lungs, 1.48%ID/g, remained relatively constant over a 24-h period
      suggesting that the complex had accumulated in the lungs in the form of
      particulates, and could not be cleared by the test subjects. The t1/2 for the
      heart and lungs was greater than 24 h. Excretion of the test compound is
      seemingly via the kidneys, but is slow with approximately 30% of the ID excreted
      within 24 h. 

PMID- 24285533
TI  - Imaging agent of a TRPA1 inhibitor.
AB  - A method for the preparation of [3'-(3) H]-4-(2'-chloro-6'-hydroxyphenyl)-2
      thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5(2H)-one (1), a TRPA1 inhibitor,
      was developed for the evaluation of imaging properties of a class of TRPA1
      inhibitors. 1 was prepared via tritiation of a protected benzaldehyde followed by
      a tetrachlorosilane catalyzed multicomponent one-step fusion and was obtained at
      a specific activity of 0.9 TBq/mmol. A (3) H-NMR spectrum on 13.5 MBq at 75 MUM
      was recorded.

PMID- 24285535
TI  - A facile strategy to fabricate thermoresponsive polymer functionalized CdTe/ZnS
      quantum dots: assemblies and optical properties.
AB  - Novel thermoresponsive CdTe/ZnS quantum dots (QDs) decorated with a copolymer
      ligand (CPL) containing 8-hydroxyquinoline and NIPAM units are prepared through
      coordinate bonding in aqueous solution. The dependence of the morphology and
      optical properties of the QDs/CPL assemblies formed via coordinate bonding on the
      experimental conditions is studied. The coordinate induced self-assemblies are
      observed by controlling the molar ratio of QDs and CPL. The self-organized
      structure of QDs/CPL proceeds through a first step of QDs-chains, followed by a
      necklace-like single annular chain, and subsequently increases its annular chain
      structure, forming a network. The CPL functionalized QDs can emit multiple colors
      from the cooperating interaction between the inherent emission (606 nm) of the
      QDs and the surface-coordinated emission (517 nm) of the CPL complex formed on
      the QD surface. For QDs-CPL systems, both Forster resonance energy transfer
      (FRET) and a high rate of photoinduced electron transfer (PET) are simultaneous,
      the latter mainly contributing to PL quenching. The thermoresponsive QDs/CPL
      assemblies also exhibit dual reversible PL properties between the inherent
      emission of QDs and surface-coordinated emission. 

PMID- 24285536
TI  - 'Lead us not into temptation': adolescence and alcohol policy in Europe.
AB  - Although the World Health Organization and the European Community recognize harm
      to children and young people due to alcohol-whether their own or someone else's
      drinking-effective policies to reduce harm are not widely followed. The alcohol
      beverage industry's drive to use social networking systems blurs the line between
      user-generated and industry marketing materials, such that young people are more
      frequently and at a younger age, potentially exposed to the promotion of
      alcoholic drinks. This contravenes recommendations arising out of the emerging
      scientific literature that delaying the onset of drinking and reducing the
      prevalence of heavy session drinking are likely to promote a healthier next
      generation. 

PMID- 24285537
TI  - Identification and characterization of functionally critical, conserved motifs in
      the internal repeats and N-terminal domain of yeast translation initiation factor
      4B (yeIF4B).
AB  - eIF4B has been implicated in attachment of the 43 S preinitiation complex (PIC)
      to mRNAs and scanning to the start codon. We recently determined that the
      internal seven repeats (of ~26 amino acids each) of Saccharomyces cerevisiae
      eIF4B (yeIF4B) compose the region most critically required to enhance mRNA
      recruitment by 43 S PICs in vitro and stimulate general translation initiation in
      yeast. Moreover, although the N-terminal domain (NTD) of yeIF4B contributes to
      these activities, the RNA recognition motif is dispensable. We have now
      determined that only two of the seven internal repeats are sufficient for wild
      type (WT) yeIF4B function in vivo when all other domains are intact. However,
      three or more repeats are needed in the absence of the NTD or when the functions
      of eIF4F components are compromised. We corroborated these observations in the
      reconstituted system by demonstrating that yeIF4B variants with only one or two
      repeats display substantial activity in promoting mRNA recruitment by the PIC,
      whereas additional repeats are required at lower levels of eIF4A or when the NTD
      is missing. These findings indicate functional overlap among the 7-repeats and
      NTD domains of yeIF4B and eIF4A in mRNA recruitment. Interestingly, only three
      highly conserved positions in the 26-amino acid repeat are essential for function
      in vitro and in vivo. Finally, we identified conserved motifs in the NTD and
      demonstrate functional overlap of two such motifs. These results provide a
      comprehensive description of the critical sequence elements in yeIF4B that
      support eIF4F function in mRNA recruitment by the PIC. 

PMID- 24285538
TI  - Unremodeled and remodeled cardiolipin are functionally indistinguishable in
      yeast.
AB  - After biosynthesis, an evolutionarily conserved acyl chain remodeling process
      generates a final highly homogeneous and yet tissue-specific molecular form of
      the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different
      organisms, and even different tissues within the same organism, contain a
      distinct collection of attached acyl chains. This observation is the basis for
      the widely accepted paradigm that the acyl chain composition of cardiolipin is
      matched to the unique mitochondrial demands of a tissue. For this hypothesis to
      be correct, cardiolipin molecules with different acyl chain compositions should
      have distinct functional capacities, and cardiolipin that has been remodeled
      should promote cardiolipin-dependent mitochondrial processes better than its
      unremodeled form. However, functional disparities between different molecular
      forms of cardiolipin have never been established. Here, we interrogate this
      simple but crucial prediction utilizing the best available model to do so,
      Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and
      remodeled cardiolipin, which differ markedly in their acyl chain composition, to
      support mitochondrial activities known to require cardiolipin. Surprisingly,
      defined changes in the acyl chain composition of cardiolipin do not alter either
      mitochondrial morphology or oxidative phosphorylation. Importantly, preventing
      cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the
      causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus,
      our data do not support the prevailing hypothesis that unremodeled cardiolipin is
      functionally distinct from remodeled cardiolipin, at least for the functions
      examined, suggesting alternative physiological roles for this conserved pathway. 

PMID- 24285539
TI  - Liver kinase B1 expression promotes phosphatase activity and abrogation of
      receptor tyrosine kinase phosphorylation in human cancer cells.
AB  - Aberrant receptor tyrosine kinase phosphorylation (pRTK) has been associated with
      diverse pathological conditions, including human neoplasms. In lung cancer,
      frequent liver kinase B1 (LKB1) mutations correlate with tumor progression, but
      potential links with pRTK remain unknown. Heightened and sustained receptor
      activation was demonstrated by LKB1-deficient A549 (lung) and HeLaS3 (cervical)
      cancer cell lines. Depletion (siRNA) of endogenous LKB1 expression in H1792 lung
      cancer cells also correlated with increased pRTK. However, ectopic LKB1
      expression in A549 and HeLaS3 cell lines, as well as H1975 activating-EGF
      receptor mutant lung cancer cell resulted in dephosphorylation of several tumor
      enhancing RTKs, including EGF receptor, ErbB2, hepatocyte growth factor receptor
      (c-Met), EphA2, rearranged during transfection (RET), and insulin-like growth
      factor I receptor. Receptor abrogation correlated with attenuation of phospho-Akt
      and increased apoptosis. Global phosphatase inhibition by orthovanadate or
      depletion of protein tyrosine phosphatases (PTPs) resulted in the recovery of
      receptor phosphorylation. Specifically, the activity of SHP-2, PTP-1beta, and PTP
      PEST was enhanced by LKB1-expressing cells. Our findings provide novel insight on
      how LKB1 loss of expression or function promotes aberrant RTK signaling and rapid
      growth of cancer cells. 

PMID- 24285540
TI  - Mechanoregulation of h2-calponin gene expression and the role of Notch signaling.
AB  - The essential role of mechanical signals in regulating the function of living
      cells is universally observed. However, how mechanical signals are transduced in
      cells to regulate gene expression is largely unknown. We previously demonstrated
      that the gene encoding h2-calponin (Cnn2) is sensitively regulated by mechanical
      tension. In the present study, mouse genomic DNA containing the Cnn2 promoter was
      cloned, and a nested set of 5' truncations was studied. Transcriptional activity
      of the Cnn2 promoter-reporter constructs was examined in transfected NIH/3T3,
      HEK293, and C2C12 cells for their responses to the stiffness of culture
      substrate. The results showed significant transcriptional activities of the -1.00
      and -1.24-kb promoter constructs, whereas the -0.61-kb construct was inactive.
      The -1.38-, -1.57-, and -2.12-kb constructs showed higher transcriptional
      activity, whereas only the -1.57- and -2.12-kb constructs exhibited repression of
      expression when the host cells were cultured on low stiffness substrate. Internal
      deletion of the segment between -1.57 and -1.38 kb in the -2.12-kb promoter
      construct abolished the low substrate stiffness-induced repression. Site-specific
      deletion or mutation of an HES-1 transcription factor binding site in this region
      also abolished this repression effect. The level of HES-1 increased in cells
      cultured under a low tension condition, corresponding to the down-regulation of
      h2-calponin. h2-Calponin gene expression is further affected by the treatment of
      cells with Notch inhibitor and activator, suggesting an upstream signaling
      mechanism. 

PMID- 24285541
TI  - Structural determinants for the interaction of formyl peptide receptor 2 with
      peptide ligands.
AB  - Unlike formyl peptide receptor 1 (FPR1), FPR2/ALX (FPR2) interacts with peptides
      of diverse sequences but has low affinity for the Escherichia coli-derived
      chemotactic peptide fMet-Leu-Phe (fMLF). Using computer modeling and site
      directed mutagenesis, we investigated the structural requirements for FPR2 to
      interact with formyl peptides of different length and composition. In calcium
      flux assay, the N-formyl group of these peptides is necessary for activation of
      both FPR2 and FPR1, whereas the composition of the C-terminal amino acids appears
      more important for FPR2 than FPR1. FPR2 interacts better with pentapeptides
      (fMLFII, fMLFIK) than tetrapeptides (fMLFK, fMLFW) and tripeptide (fMLF) but only
      weakly with peptides carrying negative charges at the C terminus (e.g. fMLFE). In
      contrast, FPR1 is less sensitive to negative charges at the C terminus. A CXCR4
      based homology model of FPR1 and FPR2 suggested that Asp-281(7.32) is crucial for
      the interaction of FPR2 with certain formyl peptides as its negative charge may
      be repulsive with the terminal COO- group of fMLF and negatively charged Glu in
      fMLFE. Asp-281(7.32) might also form a stable interaction with the positively
      charged Lys in fMLFK. Site-directed mutagenesis was performed to remove the
      negative charge at position 281 in FPR2. The D281(7.32)G mutant showed improved
      affinity for fMLFE and fMLF and reduced affinity for fMLFK compared with wild
      type FPR2. These results indicate that different structural determinants are used
      by FPR1 and FPR2 to interact with formyl peptides. 

PMID- 24285543
TI  - WITHDRAWN: Blm10-proteasomes antagonize mitochondrial fission through degradation
      of Dnm1.
AB  - This manuscript was withdrawn by the author.

PMID- 24285542
TI  - S100A14, a member of the EF-hand calcium-binding proteins, is overexpressed in
      breast cancer and acts as a modulator of HER2 signaling.
AB  - HER2 is overexpressed in 20-25% of breast cancers. Overexpression of HER2 is an
      adverse prognostic factor and correlates with decreased patient survival. HER2
      stimulates breast tumorigenesis via a number of intracellular signaling
      molecules, including PI3K/AKT and MAPK/ERK.S100A14,one member of the S100 protein
      family, is significantly associated with outcome of breast cancer patients. Here,
      for the first time, we show that S100A14 and HER2 are coexpressed in invasive
      breast cancer specimens,andthere is a significant correlation between the
      expression levels of the two proteins by immunohistochemistry. S100A14 and HER2
      are colocalized in plasma membrane of breast cancer tissue cells and breast
      cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to
      HER2 by co-immunoprecipitation and pull-down assays. Further study shows that
      residues 956-1154 of the HER2 intracellular domain and residue 83 of S100A14 are
      essential for the two proteins binding.Moreover,we observe a decrease of HER2
      phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in
      S100A14-silenced MCF-7, BT474, and SK-BR3 cells. Our findings suggest that
      S100A14 functions as a modulator of HER2 signaling and provide mechanistic
      evidence for its role in breast cancer progression.

PMID- 24285544
TI  - Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain
      1) and LOV2 relative to the kinase domain and regulation of kinase activity in
      Chlamydomonas phototropin.
AB  - Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive
      domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a
      BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that
      undergoes a cyclic photoreaction upon BL excitation via a signaling state in
      which the inhibition of the kinase activity by LOV2 is negated. To understand the
      molecular mechanism underlying the BL-dependent activation of the kinase, the
      photochemistry, kinase activity, and molecular structure were studied with the
      phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C.
      reinhardtii phot showed cyclic photoreaction characteristics with the activation
      of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the
      photosensitivity of the kinase activation, which was well explained by the fact
      that the signaling state lasted for a shorter period of time compared with that
      of the phot. Small angle x-ray scattering revealed monomeric forms of the
      proteins in solution and detected BL-dependent conformational changes, suggesting
      an extension of the global molecular shapes of both samples. Constructed
      molecular model of full-length phot based on the small angle x-ray scattering
      data proved the arrangement of LOV1, LOV2, and KD for the first time that showed
      a tandem arrangement both in the dark and under BL irradiation. The models
      suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation.
      This finding demonstrates that LOV1 may interact with LOV2 and modify the
      photosensitivity of the kinase activation through alteration of the duration of
      the signaling state in LOV2. 

PMID- 24285545
TI  - Regulation of mitochondrial antiviral signaling (MAVS) expression and signaling
      by the mitochondria-associated endoplasmic reticulum membrane (MAM) protein Gp78.
AB  - In a previous study, we identified the E3 ubiquitin ligase Gp78 by RNAi high
      throughput screening as a gene whose depletion restricted enterovirus infection.
      In the current study, we show that Gp78, which localizes to the ER-mitochondria
      interface, is a regulator of RIG-I-like receptor (RLR) antiviral signaling. We
      show that depletion of Gp78 results in a robust decrease of vesicular stomatitis
      virus (VSV) infection and a corresponding enhancement of type I interferon (IFN)
      signaling. Mechanistically, we show that Gp78 modulates type I IFN induction by
      altering both the expression and signaling of the mitochondria-localized RLR
      adaptor mitochondrial antiviral signaling (MAVS). Expression of mutants of Gp78
      that abolish its E3 ubiquitin ligase and its participation in ER-associated
      degradation (ERAD) lost their ability to degrade MAVS, but surprisingly
      maintained their ability to repress RLR signaling. In contrast, Gp78 lacking its
      entire C terminus lost both its ability to degrade MAVS and repress RLR
      signaling. We show that Gp78 interacts with both the N- and C-terminal domains of
      MAVS via its C-terminal RING domain, and that this interaction is required to
      abrogate Gp78-mediated attenuation of MAVS signaling. Our data thus implicate two
      parallel pathways by which Gp78 regulates MAVS signaling; one pathway requires
      its E3 ubiquitin ligase and ERAD activity to directly degrade MAVS, whereas the
      other pathway occurs independently of these activities, but requires the Gp78
      RING domain and occurs via a direct association between this region and MAVS. 

PMID- 24285546
TI  - A novel non-canonical forkhead-associated (FHA) domain-binding interface mediates
      the interaction between Rad53 and Dbf4 proteins.
AB  - Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains are overrepresented
      in DNA damage and replication stress response proteins. They function primarily
      as phosphoepitope recognition modules but can also mediate non-canonical
      interactions. The latter are rare, and only a few have been studied at a
      molecular level. We have identified a crucial non-canonical interaction between
      the N-terminal FHA1 domain of the checkpoint effector kinase Rad53 and the BRCT
      domain of the regulatory subunit of the Dbf4-dependent kinase that is critical to
      suppress late origin firing and to stabilize stalled forks during replication
      stress. The Rad53-Dbf4 interaction is phosphorylation-independent and involves a
      novel non-canonical interface on the FHA1 domain. Mutations within this surface
      result in hypersensitivity to genotoxic stress. Importantly, this surface is not
      conserved in the FHA2 domain of Rad53, suggesting that the FHA domains of Rad53
      gain specificity by engaging additional interaction interfaces beyond their
      phosphoepitope-binding site. In general, our results point to FHA domains
      functioning as complex logic gates rather than mere phosphoepitope-targeting
      modules. 

PMID- 24285548
TI  - Codeletions at 1p and 19q predict a lower risk of pseudoprogression in
      oligodendrogliomas and mixed oligoastrocytomas.
AB  - BACKGROUND: Pseudoprogression (PsP) occurs at a higher rate in glioblastoma
      multiforme with a methylated MGMT promoter-a subset with increased sensitivity to
      chemoradiotherapy and better overall prognosis. In oligodendroglioma (OG) and
      oligoastrocytoma (OA), presence of 1p/19q codeletions is highly predictive of
      response to treatment and is often associated with the methylated MGMT promoter;
      hence, this study queries whether the presence of 1p/19q codeletions in OG/OA
      correlates with a higher rate of PsP following therapy. METHODS: A retrospective
      analysis was performed on all OG/OA in a database of patients with brain tumors
      who underwent resection of their tumor since 1998. Eighty-eight cases (37 with
      and 51 without 1p/19q codeletions) met inclusion criteria, and their patient data
      were analyzed to determine whether the presence of 1p/19q codeletions was
      associated with PsP and survival. RESULTS: OG/OA (World Health Organization
      grades II and III) with 1p/19q codeletions had a significantly improved survival
      (P = .041). Multivariate analysis found that PsP occurred less frequently in
      OG/OA with 1p/19q codeletions compared with tumors without codeletions (odds
      ratio, 0.047; 95% confidence interval, 0.005-0.426; P = .0066). The rate of PsP
      was 19% for the entire cohort, 31% for tumors without codeletions, and 3% for
      tumors with codeletions. When early posttreatment contrast enhancement developed
      in tumors with 1p/19q codeletions, it occurred exclusively in tumors that were
      histologically OA and not OG. CONCLUSION: Codeletions of 1p/19q are a marker of
      good prognosis but are unexpectedly associated with a lower likelihood of PsP.
      PsP does not correlate with sensitivity to treatment and improved survival in
      OG/OA.

PMID- 24285547
TI  - H3F3A K27M mutations in thalamic gliomas from young adult patients.
AB  - INTRODUCTION: Mutations in H3F3A, which encodes histone H3.3, commonly occur in
      pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas
      that arise at midline locations (eg, pons, thalamus, spine); moreover, this
      substitution occurs mainly in tumors in children and adolescents. Here, we sought
      to determine the association between H3F3A mutations and adult thalamic glioma.
      METHODS: Genomic H3F3A was sequenced from 20 separate thalamic gliomas.
      Additionally, for 14 of the 20 gliomas, 639 genes--including cancer-related genes
      and chromatin-modifier genes--were sequenced, and the Infinium
      HumanMethylation450K BeadChip was used to examine DNA methylation across the
      genome. RESULTS: Of the 20 tumors, 18 were high-grade thalamic gliomas, and of
      these 18, 11 were from patients under 50 years of age (median age, 38 y; range,
      17-46), and 7 were from patients over 50 years of age. The H3F3A K27M mutation
      was present in 10 of the 11 (91%) younger patients and absent from all 7 older
      patients. Additionally, H3F3A K27M was not detected in the 2 diffuse
      astrocytomas. Further sequencing revealed recurrent mutations in TP53, ATRX, NF1,
      and EGFR. Gliomas with H3F3A K27M from pediatric or young adult patients had
      similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas
      with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric
      glioblastomas. CONCLUSION: We found that high-grade thalamic gliomas from young
      adults, like those from children and adolescents, frequently had H3F3A K27M.

PMID- 24285549
TI  - Evidence of association of human papillomavirus with prognosis worsening in
      glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant brain tumor in
      adults, but its etiology still remains unknown. Recently, a role of viruses such
      as cytomegalovirus and JC virus in gliomagenesis has been suggested. Since human
      papillomavirus (HPV) is considered the most common oncogenic virus in humans, we
      evaluated its occurrence in GBM samples. MATERIAL AND METHODS: Fifty-two formalin
      fixed paraffin-embedded primary glioblastoma specimens were retrospectively
      analyzed. The presence of HPV genome on tumor DNA was assessed by MY/GP nested
      PCR. Confirmation of HPV detection was obtained by chromogenic in situ
      hybridization (CISH) and immunohistochemistry (IHC) with an antibody directed
      against the L1 capsidic protein. Finally, univariate and multivariate
      proportional-hazards models were used to compare the risk of death among HPV
      positive and HPV-negative patients. RESULTS: Strikingly, viral DNA was detected
      after PCR in 12 cases (23%). HPV16 genome was present in 25% infected samples,
      whereas the remaining samples tested positive for HPV6. CISH confirmed positivity
      in all infected samples for which enough material was available. Moreover, IHC
      positivity suggested that production of viral proteins from HPV genome is an
      ongoing process in GBM cancer cells. Finally an association between HPV infection
      and a worse prognosis was found in patients upon age stratification with a
      univariate analysis (HR, 2.10; 95% CI, 1.00-4.44; log-rank P = .045).
      CONCLUSIONS: HPV infection status may be considered an independent prognostic
      factor in GBM patients and suggests that prevention may be considered, should HPV
      be recognized as a causative agent in gliomagenesis.

PMID- 24285551
TI  - Extended self-ordering regime in hard anodization and its application to make
      asymmetric AAO membranes for large pitch-distance nanostructures.
AB  - We report here a fast and reliable hard anodization process to make asymmetric
      anodic aluminum oxide (AAO) membranes which can serve as a template for large
      pitch-distance nanostructures. In order to make larger pitch distances possible,
      the common burning failure associated with the high current density during the
      conventional constant voltage hard anodization, especially at a voltage higher
      than a known limit, i.e., 155 V for oxalic acid, was effectively suppressed by
      using a burning-protective agent. A new self-ordering regime beyond the voltage
      limit was observed with a different voltage-interpore distance relationship of
      2.2 nm V(-1) compared to the reported 2.0 nm V(-1) for hard anodization.
      Combining a sulfuric acid mild anodization with this new regime of hard
      anodization, we further demonstrate a scalable process to make an asymmetric
      membrane with size up to ~47 mm in diameter and ~60 MUm in thickness. This free
      standing membrane can be used as a template for novel nanopatterned structures
      such as arrays of quantum dots, nanowires or nanotubes with diameters of a few
      tens of nanometers and pitch distance of over 400 nm.

PMID- 24285552
TI  - Distributed computing and data storage in proteomics: many hands make light work,
      and a stronger memory.
AB  - Modern day proteomics generates ever more complex data, causing the requirements
      on the storage and processing of such data to outgrow the capacity of most
      desktop computers. To cope with the increased computational demands, distributed
      architectures have gained substantial popularity in the recent years. In this
      review, we provide an overview of the current techniques for distributed
      computing, along with examples of how the techniques are currently being employed
      in the field of proteomics. We thus underline the benefits of distributed
      computing in proteomics, while also pointing out the potential issues and
      pitfalls involved. 

PMID- 24285550
TI  - Establishing percent resection and residual volume thresholds affecting survival
      and recurrence for patients with newly diagnosed intracranial glioblastoma.
AB  - INTRODUCTION: Surgery is first-line therapy for glioblastoma, and there is
      evidence that gross total resection is associated with improved survival. Gross
      total resection, however, is not always possible, and relationships among extent
      (percent) of resection (EOR), residual volume (RV), and survival are unknown. The
      goals were to evaluate whether there is an association between EOR and RV with
      survival and recurrence and to establish minimum EOR and maximum RV thresholds.
      METHODS: Adult patients who underwent primary glioblastoma surgery from 2007 to
      2011 were retrospectively reviewed. Three-dimensional volumetric tumor
      measurements were made. Multivariate proportional hazards regression analysis was
      used to evaluate the relationship between EOR and RV with survival and
      recurrence. RESULTS: Of 259 patients, 203 (78%) died and 156 (60%) had tumor
      recurrence. The median survival and progression-free survival were 13.4 and 8.9
      months, respectively. The median (interquartile range) pre- and postoperative
      tumor volumes were 32.2 (14.0-56.3) and 2.1 (0.0-7.9) cm(3), respectively. EOR
      was independently associated with survival (hazard ratio [HR], 0.995; 95%
      confidence interval [CI]: 0.990-0.998; P = .008) and recurrence (HR [95% CI],
      0.992 [0.983-0.998], P = .005). The minimum EOR threshold for survival (P =
      .0006) and recurrence (P = .005) was 70%. RV was also associated with survival
      (HR [95% CI], 1.019 [1.006-1.030], P = .004) and recurrence (HR [95% CI], 1.024
      [1.001-1.044], P = .03). The maximum RV threshold for survival (P = .01) and
      recurrence (P = .01) was 5 cm(3). CONCLUSION: This study shows for the first time
      that both EOR and RV are significantly associated with survival and recurrence,
      where the thresholds are 70% and 5 cm(3), respectively. These findings may help
      guide surgical and adjuvant therapies aimed at optimizing outcomes for
      glioblastoma patients.

PMID- 24285553
TI  - The application of humanization theory to health-promoting practice.
AB  - It has been identified that if public health interventions do not account for
      what it means to be human, they are likely to fail. The aim of this article is to
      introduce humanization theory and to show how it can be applied to health
      promoting practice. Health promotion can feature humanizing and dehumanizing
      elements, and these appear to impact on how people may (or may not) engage with
      interventions. The primary prevention of skin cancer in young people is an
      illustration of this. The practice implications of applying humanization theory
      to health promotion are potentially vast and complex; however, it is proposed
      that considering the dimensions of humanization may be a useful activity to
      inform the early stages of health-promotion intervention designs. Furthermore,
      developing the qualitative research evidence base about peoples' experiences of
      humanizing dimensions of health promotion would also be a valuable step towards
      ensuring that interventions account for the 'human dimension'. Applying
      humanization theory to the specific example of skin cancer prevention in young
      people has been a new venture but based on work so far, suggestions for
      humanizing principles for skin cancer prevention would need to be inclusive of
      the needs of young people, to support them and to involve them in research and
      intervention development. 

PMID- 24285554
TI  - CASALUD: an innovative health-care system to control and prevent non-communicable
      diseases in Mexico.
AB  - Mexico and other Latin American countries are currently facing a dramatic
      increase in the number of adults suffering from non-communicable diseases (NCDs)
      such as diabetes, cardiovascular disease (CVD) and chronic kidney disease (CKD),
      which require prolonged, continuous care. This epidemiological shift has created
      new challenges for health-care systems. Both the World Health Organization (WHO)
      and the United Nations (UN) have recognised the growing human and economic costs
      of NCDs and outlined an action plan, recognising that NCDs are preventable, often
      with common preventable risk factors linked to risky health behaviours. In line
      with international best practices, Mexico has applied a number of approaches to
      tackle these diseases. However, challenges remain for the Mexican health-care
      system, and in planning a strategy for combating and preventing NCDs, it must
      consider how best to integrate these strategies with existing health-care
      infrastructure. Shifting the paradigm of care in Mexico from a curative, passive
      approach to a preventive, proactive model will require an innovative and
      replicable system that guarantees availability of medicines and services,
      strengthens human capital through ongoing professional education, expands early
      and continuous access to care through proactive prevention strategies and
      incorporates technological innovations in order to do so. Here, we describe
      CASALUD: an innovative model in health-care that leverages international best
      practices and uses innovative technology to deliver NCD care, control and
      prevention. In addition, we describe the lessons learned from the initial
      implementation of the model for its effective use in Mexico, as well as the plans
      for wider implementation throughout the country, in partnership with the Mexican
      Ministry of Health. 

PMID- 24285555
TI  - Anatomical and pharmacological characterization of catecholamine transients in
      the medial prefrontal cortex evoked by ventral tegmental area stimulation.
AB  - Voltammetric measurements of catecholamines in the medial prefrontal cortex
      (mPFC) are infrequent because of lack of chemical selectivity between dopamine
      and norepinephrine and their overlapping anatomical inputs. Here, we examined the
      contribution of norepinephrine to the catecholamine release in the mPFC evoked by
      electrical stimulation of the ventral tegmental area (VTA). Initially, electrical
      stimulation was delivered in the midbrain at incremental depths of -5 to -9.4 mm
      from bregma while catecholamine release was monitored in the mPFC. Although
      catecholamine release was observed at dorsal stimulation sites that may
      correspond to the dorsal noradrenergic bundle (DNB, containing noradrenergic
      axonal projections to the mPFC), maximal release was evoked by stimulation of the
      VTA (the source of dopaminergic input to the mPFC). Next, VTA-evoked
      catecholamine release was monitored in the mPFC before and after knife incision
      of the DNB, and no significant changes in the evoked catecholamine signals were
      found. These data indicated that DNB fibers did not contribute to the VTA-evoked
      catecholamine release observed in the mPFC. Finally, while the D2-receptor
      antagonist raclopride significantly altered VTA-evoked catecholamine release, the
      alpha2-adrenergic receptor antagonist idazoxan did not. Specifically, raclopride
      reduced catecholamine release in the mPFC, opposite to that observed in the
      striatum, indicating differential autoreceptor regulation of mesocortical and
      mesostriatal neurons. Together, these findings suggest that the catecholamine
      release in the mPFC arising from VTA stimulation was predominately dopaminergic
      rather than noradrenergic.

PMID- 24285556
TI  - Label-free relative quantification of alpha-2-macroglobulin site-specific core
      fucosylation in pancreatic cancer by LC-MS/MS.
AB  - We describe a label-free relative quantification LC-MS/MS method for core
      fucosylation in alpha-2-macroglobulin (A2MG) immunoprecipitated from human sera.
      The method utilizes endoglycosidase F partial deglycosylation to reduce
      glycosylation microheterogeneity, while retaining the innermost N
      acetylglucosamine (GlcNAc) and core fucose. Precursor ion peak areas of partially
      deglycosylated peptides were obtained and site-specific core-fucosylation ratios
      based on the peak areas of core-fucosylated and nonfucosylated counterparts were
      calculated and evaluated for assay development. This assay was applied in a
      preliminary study of sera samples from normal controls and patients with
      pancreatic diseases, including pancreatic cancer and chronic pancreatitis. A2MG
      fucosylation levels at sites N396 and N1424 were found to decrease in both
      chronic pancreatitis and pancreatic cancer compared to normal controls. The two
      sites were identified by two peptides and their core-fucosylation ratios were
      found to be internally consistent. This method provides a platform to quantify
      fucosylation levels and can be used to study site-specific core-fucosylation
      aberrations in other glycoproteins for other diseases. 

PMID- 24285561
TI  - Feasibility and safety of transfemoral implantation of Edwards SAPIEN XT
      prosthesis without balloon valvuloplasty in severe stenosis of native aortic
      valve.
AB  - OBJECTIVES: Balloon valvuloplasty (BV) before transcatheter aortic implantation
      has been thought to be mandatory before the valve is implanted. We have explored
      the feasibility and safety of direct implantation of balloon expandable Edwards
      SAPIEN XT valve without prior balloon dilatation. BACKGROUND: Some complications
      after transcatheter aortic valve replacement (TAVR) have been associated with
      unwanted effects of BV, mainly the contribution to stroke and severe aortic
      regurgitation (AR) before the valve is implanted. Direct implantation with a self
      expanding aortic valve has been recently reported. METHODS: From November 2011 to
      April 2012, ten patients were selected that met the following criteria in the
      transesophageal echocardiography (TEE): moderate calcification, homogeneous
      distribution of calcium, symmetrical opening of the valve, and some degree of
      aortic insufficiency. RESULTS: All patients had symptomatic aortic stenosis of a
      native valve and high surgical risk; six patients had the valve mildly calcified,
      in four patients the degree of calcification was moderate. The native valve was
      crossed and the prosthetic aortic valve was properly positioned in all cases and
      implanted in the correct position. No patient underwent post-dilatation and
      trivial AR was present in four patients. There were no adverse events (death,
      need for pacemaker, myocardial infarction, or stroke). At 30 days post-procedure,
      all patients were alive and had significant clinical improvement. CONCLUSIONS:
      Direct implantation of Edwards SAPIEN XT without prior BV in selected cases is
      feasible and safe. The number of patients in whom this technique would be
      applicable, and their impact on reducing complications has to be determined.

PMID- 24285562
TI  - A facile method for preparing porous, optically active, magnetic Fe3 O4 @poly(N
      acryloyl-leucine) inverse core/shell composite microspheres.
AB  - The first synthesis of porous, optically active, magnetic Fe3 O4 @poly(N-acryloyl
      leucine) inverse core/shell composite microspheres is reported, in which the core
      is constructed of chiral polymer and the shell is constructed of Fe3 O4 NPs. The
      microspheres integrate three significant concepts, "porosity", "chirality", and
      "magneticity", in one single microspheric entity. The microspheres consist of Fe3
      O4 nanoparticles and porous optically active microspheres, and thus combine the
      advantages of both magnetic nanoparticles and porous optically active
      microspheres. The pore size and specific surface area of the microspheres are
      characterized by N2 adsorption, from which it is found that the composite
      microspheres possess a desirable porous structure. Circular dichroism and UV-vis
      absorption spectroscopy measurements demonstrate that the microspheres exhibit
      the expected optical activity. The microspheres also have high saturation
      magnetization of 14.7 emu g(-1) and rapid magnetic responsivity. After further
      optimization, these novel microspheres may potentially find applications in areas
      such as asymmetric catalysis, chiral adsorption, etc. 

PMID- 24285563
TI  - Soluble interleukin-6 receptor level reflecting the illness activity in bipolar
      disorder.

PMID- 24285564
TI  - Mirtazapine associated tender pitting pedal oedema.

PMID- 24285565
TI  - Outcome of mood disorders before psychopharmacology: a systematic review.
AB  - OBJECTIVES: This paper systematically reviews all outcome studies of patients
      with mood disorders treated prior to the widespread use of antidepressants, mood
      stabilizers, and major tranquillizers. The aim is to estimate recovery and
      sustained recovery rates and to provide some evidence about the efficacy of
      modern drug treatments in changing the long-term outcome of mood disorders.
      METHODS: MEDLINE and PSYCHINFO searches for studies on mood disorders published
      prior to 1970 were performed. Most studies were obtained by hand searching and
      extensive cross referencing. Information was independently extracted by the two
      authors. RESULTS: A total of 29 relevant articles were obtained. The studies
      reviewed over 14,000 patients in total. Patients were mainly inpatients with a
      predominance of females. The majority of patients suffered from depression. The
      cohorts were followed up for 1-30 years. The median rate of recovery was 69%
      (range 17-91%). The time to recovery was generally several months. The median
      rate of recovering and remaining well was 51% (range 21-67%). CONCLUSIONS: The
      median rate of recovery is less than modern cohorts and the time to recovery
      longer. However, the rate of recovering and remaining well appears high compared
      to modern cohorts, although this result may reflect methodological issues. This
      review provides no support to the belief that pharmacological treatments have
      resulted in an improvement in the long-term outcome of patients with mood
      disorders.

PMID- 24285566
TI  - Ciliary genes TBC1D32/C6orf170 and SCLT1 are mutated in patients with OFD type
      IX.
AB  - Clinical syndromes caused by defects in the primary cilium are heterogeneous but
      there are recurrent phenotypic manifestations that define them as a collective
      group known as ciliopathies. Dozens of genes have been linked to various
      ciliopathies but large patient cohorts have clearly revealed the existence of
      additional genetic heterogeneity, which is yet to be fully appreciated. In our
      search for novel ciliopathy-linked genes through the study of unmapped ciliopathy
      phenotypes, we have identified two simplex cases with a severe ciliopathy
      phenotype consistent with oro-facio-digital syndrome type IX featuring midline
      cleft, microcephaly, and colobomatous microphathalmia/anophthalmia. In addition,
      there was variable presence of polydactyly, absent pituitary, and congenital
      heart disease. The autozygome of each index harbored a single novel truncating
      variant as revealed by exome sequencing, and the affected genes (SCLT1 and
      TBC1D32/C6orf170) have established roles in centrosomal biology and ciliogenesis.
      Our findings suggest a previously unrecognized role of SCLT1 and TBC1D32 in the
      pathogenesis of ciliopathy in humans. 

PMID- 24285567
TI  - Cannabinoids and the endocannabinoid system in lower urinary tract function and
      dysfunction.
AB  - AIMS: To review knowledge on cannabinoids and the endocannabinoid system in lower
      urinary tract function and dysfunction. METHODS: Review of MEDLINE using defined
      search terms, and manual analysis. Articles published in English were included.
      RESULTS AND DISCUSSION: Components of the endocannabinoid system-cannabinoid
      (CB)receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH),
      which degrades anandamide and related fatty-acid amides-have been located to
      lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have
      located CB receptors in urothelium and sensory nerves and FAAH in the urothelium.
      CB receptor- and FAAH-related activities have also been reported in the
      lumbosacral spinal cord. Data on supraspinal CB functions in relation to
      micturition are lacking. Cannabinoids are reported to reduce sensory activity of
      isolated tissues, cause antihyperalgesia in animal studies of bladder
      inflammation, affect urodynamics parameters reflecting sensory functions in
      animals models, and appear to have effects on storage symptoms in humans. FAAH
      inhibitors have affected sensory bladder functions and reduced bladder
      overactivity in rat models. Cannabinoids may modify nerve-mediated functions of
      isolated lower urinary tract tissues. CONCLUSIONS: Evidence suggests components
      of the endocannabinoid system are involved in regulation of bladder function,
      possibly at several levels of the micturition pathway. It is unclear if either CB
      receptor has a dominant role in modification of sensory signals or if differences
      exist at peripheral and central nervous sites. Amplification of endocannabinoid
      activity by FAAH inhibitors may be an attractive drug target in specific pathways
      involved in LUTS.

PMID- 24285568
TI  - A neutral supramolecular hyperbranched polymer fabricated from an AB2 -type
      copillar[5]arene.
AB  - A heterotritopic copillar[5]arene monomer by introducing effective neutral guest
      moieties (methylene chains end-capped with cyano and triazole groups) to a
      pillar[5]arene macrocycle is prepared. This well-designed AB2 -type
      copillar[5]arene contains strong host-guest recognition motifs that are connected
      with relatively flexible and long linkers, thus efficiently assembles to form
      supramole-cular hyperbranched polymer (SHP) in chloroform solution, which is
      characterized by various techniques including (1) H NMR, DOSY, viscosity, DLS,
      and TEM. Particularly, this supramolecular polymer can be effectively
      depolymerized by adding a competitive butanedinitrile guest. 

PMID- 24285569
TI  - Multiple Plantago species (Plantaginaceae) modify floral reflectance and color in
      response to thermal change.
AB  - PREMISE OF THE STUDY: Understanding how plant reproduction responds to
      temperature has become increasingly important because of global climate change.
      Temperature-sensitive plasticity in floral reflectance is likely involved in some
      of these responses. Such plasticity, which underlies thermoregulatory ability,
      affects reproductive success in Plantago lanceolata. To see whether other
      Plantago species also show thermal plasticity in reflectance, we measured
      plasticity in P. lagopus, P. coronopus, P. major, P. subulata, P. albicans, P.
      tomentosa, P. maritima, and P. weldenii. METHODS: We induced plants to flower at
      two temperatures in growth chambers and recorded floral reflectance (362-800 nm).
      KEY RESULTS: All species were thermally plastic in visible and near-IR regions.
      Species and populations differed in response. Some showed greater variation in
      reflectance at warm temperature, while the reverse was true for others.
      Plasticity was greatest in the P. lanceolata clade. Cosmopolitan species were not
      more plastic than were geographically restricted species. CONCLUSIONS: The data
      suggest that (1) thermal plasticity is an ancestral trait for Plantago, (2)
      plasticities in visible and near-IR regions have evolved along different pathways
      within the genus, and (3) phylogenetic history partially explains this
      evolutionary divergence. Our data combined with those of previous studies suggest
      that global climate change will modify floral reflectance and color in many plant
      species. These modifications are likely to affect plant reproductive success.

PMID- 24285570
TI  - Pinaceae-like reproductive morphology in Schizolepidopsis canicularis sp. nov.
      from the Early Cretaceous (Aptian-Albian) of Mongolia.
AB  - PREMISE OF THE STUDY: Seed cone scales assigned to the genus Schizolepidopsis are
      widespread in Late Triassic to Cretaceous Eurasian deposits. They have been
      linked to the conifer family Pinaceae based on associated vegetative remains, but
      their exact affinities are uncertain. Recently discovered material from the Early
      Cretaceous of Mongolia reveals important new information concerning
      Schizolepidopsis cone scales and seeds, and provides support for a relationship
      between the genus and extant Pinaceae. METHODS: Specimens were collected from
      Early Cretaceous (probable Aptian-Albian) lignite deposits in central Mongolia.
      Lignite samples were disaggregated, cleaned in hydrofluoric acid, and washed in
      water. Specimens were selected for further study using light and electron
      microscopy. KEY RESULTS: Schizolepidopsis canicularis seed cones consist of
      loosely arranged, bilobed ovulate scales subtended by a small bract. A single
      inverted seed with an elongate micropyle is borne on each lobe of the ovulate
      scale. Each seed has a wing formed by the separation of the adaxial surface of
      the ovulate scale. CONCLUSIONS: Schizolepidopsis canicularis produced winged
      seeds that formed in a manner that is unique to Pinaceae among extant conifers.
      We do not definitively place this species in Pinaceae pending more complete
      information concerning its pollen cones and vegetative remains. Nevertheless,
      this material suggests that Schizolepidopsis may be important for understanding
      the early evolution of Pinaceae, and may potentially help reconcile the
      appearance of the family in the fossil record with results based on phylogenetic
      analyses of molecular data.

PMID- 24285571
TI  - The chromosome-centric human proteome project at FEBS Congress.
AB  - In the summer of 2013, distinguished global representatives of proteome science
      gathered to discuss the futuristic visions of the chromosome-centric human
      proteome project (C-HPP) (Cochairs: Y. K. Paik, G. Omenn; hosted by A. Archakov,
      Institute of Biomedical Chemistry, Russia) that was broadcast to the annual
      Federation of European Biochemical Societies Congress (St. Petersburg, Russia,
      July 10-11, 2013). Technology breakthroughs presented included a new ultra
      sensitive Tribrid mass-spectrometer from Thermo and SOMAmers-Slow Off-rate
      Modified Aptamers (SOMAlogic, USA), a new type of protein capture reagents.
      Professor Archakov's group introduced the "rectangle" concept of proteome size as
      a product of proteome width and depth. The discussion on proteome width
      culminated with the introduction of digital biomarkers-low-copied aberrant
      proteins that differ from their typical forms by PTMs, alternative splicing, or
      single amino acid polymorphisms. The aberrant proteoforms, a complement to whole
      genome proteomic surveys, were presented as an ultimate goal for the proteomic
      community. 

PMID- 24285572
TI  - Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased
      sensitivity of Gorlin syndrome patients to radiation carcinogenesis.
AB  - Human phenotypes that are highly susceptible to radiation carcinogenesis have
      been identified. Sensitive phenotypes often display robust regulation of
      molecular features that modify biological response, which can facilitate
      identification of the pathways/networks that contribute to pathophysiological
      outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin
      syndrome patients (GDFs), who display a pronounced inducible tumorigenic response
      to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our
      approach exploits newly developed thiol reactive probes to define changes in
      protein thiol profiles in live cell studies, which minimizes artifacts associated
      with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa
      protein thiol in GDFs from independent Gorlin syndrome patients, compared with
      NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase
      1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1
      protein deficiency in GDFs was confirmed by Western blot. A number of additional
      protein thiol differences in GDFs were identified, including radiation responsive
      annexin family members and lamin A/C. Collectively, candidates identified in our
      study have plausible implications for radiation health effects and cancer
      susceptibility.

PMID- 24285573
TI  - Effect of polymer porosity on aqueous self-healing encapsulation of proteins in
      PLGA microspheres.
AB  - Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique
      class of functional biomaterials capable of microencapsulating process-sensitive
      proteins by simple mixing and heating the drug-free polymer in aqueous protein
      solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks
      of varying porosity (epsilon = 0.49-73) encapsulate increasing lysozyme (~1 to
      10% w/w) with increasing epsilon, with typically ~20 to 25% pores estimated
      accessible to entry by the enzyme from the external solution. Release kinetics of
      lysozyme under physiological conditions is continuous over more than two weeks
      and most strongly influenced by epsilon and protein loading before reaching a lag
      phase until 28 d at the study completion. Recovered enzyme after release is
      typically predominantly monomeric and active. Formulations containing acid
      neutralizing MgCO3 at >= 4.3% exhibit >97% monomeric and active protein after the
      release with full mass balance recovery. Hence, control of SH polymer epsilon is
      a key parameter to development of this new class of biomaterials.

PMID- 24285574
TI  - TEM investigation on the microstructural evolution of Hastelloy N induced by Ar+
      ion irradiation.
AB  - Hastelloy N alloy has been selected as the primary structure material for molten
      salt reactor. In this article, Hastelloy N alloy samples were irradiated to
      different doses at room temperature using 300 keV Ar(+) ions. The microstructural
      evolution was investigated by transmission electron microscopy (TEM) and energy
      dispersive spectroscopy (EDS). Black dot defects emerged in sample irradiated at
      low dose (0.4 displacement per atom (dpa)), and they grew up with irradiation
      doses (0.4-2 dpa). A high density of small dislocation loops (nano meters in
      size) were observed in the sample irradiated to 4 dpa. When the ion dose
      increased to 12 dpa, complicated structures with defects (including dislocation
      lines, larger loops and smaller black dots) were observed. Dislocation networks
      were detected from high-angle annular dark field (HAADF) images. Larger
      dislocation loops (size: 30-80 nm) were visible in the sample irradiated to 40
      dpa. Irradiation with dose of 120 dpa led to the formation of face-centered cubic
      nanocrystallites with preferred orientations.

PMID- 24285575
TI  - Ionic supramolecular networks fully based on chemicals coming from renewable
      sources.
AB  - New supramolecular ionic networks are synthesized by proton transfer reaction
      between a bio-based fatty diamine molecule (Priamine 1074) and a series of
      naturally occurring carboxylic acids such as malonic acid, citric acid, tartaric
      acid, and 2,5-furandicarboxylic acid. The resulting solid soft material exhibits
      a thermoreversible transition becoming a viscoelastic liquid at high
      temperatures. All the networks show an elastic behavior at low temperatures/high
      frequencies, with elastic modulus values ranging from 4.5 * 10(6) to 4.5 * 10(7)
      Pa and soft network to liquid transitions T(nl) between -10 and 60  degrees C.
      The supramolecular ionic network based on cationic Priamine 1074 and anionic
      citrate shows promising self-healing properties at room temperature as well as
      relatively high ionic conductivity values close to 10(-6) S cm(-1).

PMID- 24285576
TI  - Penile vibratory stimulation in the treatment of post-prostatectomy incontinence:
      a randomized pilot study.
AB  - AIMS: To examine penile vibratory stimulation (PVS) in the treatment of post
      prostatectomy urinary incontinence (UI). METHODS: Patients with post
      prostatectomy UI were included in a 12-week trial. A 24-hr pad test and a 72-hr
      voiding diary were collected at baseline. Participants were randomized to receive
      PVS for the first 6 weeks (group 1) or for the final 6 weeks (group 2) of the
      study. The primary outcome was the difference in leakage between groups 1 and 2
      at 6 weeks as measured by changes in the pad test. The trial was registered at
      www.clinicaltrials.org (NCT01540656). RESULTS: Data from 31 men were available
      for analyses. The difference in the change on the pad test between the groups did
      not reach statistical significance at 6 weeks (P = 0.13) while the change in
      incontinence episodes between groups approached statistical significance (P =
      0.052). However, there was a median reduction of -33 g (P = 0.021) on the pad
      test and a median reduction in daily incontinence episodes of -1 (P = 0.023) in
      group 1 at 6 weeks. At 12 weeks, group 2 had a median decrease on the pad test of
      -8 g (P = 0.10) and no change in incontinence episodes. A pooled analysis showed
      a decline on the pad test of -13.5 g (P = 0.004) after PVS. Small improvements
      were seen in subjective symptom scores and 58% stated to be satisfied with PVS.
      Self-limiting side effects were experienced by 15% of patients. CONCLUSIONS: PVS
      is feasible in the treatment of post-prostatectomy UI. Larger trials are needed
      to document the clinical efficacy.

PMID- 24285577
TI  - One-pot synthesis of glycopolymer-porphyrin conjugate as photosensitizer for
      targeted cancer imaging and photodynamic therapy.
AB  - One-pot system combining multi-reactions is used to synthesize novel porphyrin
      glycopolymer conjugates. Sodium mercury amalgam is used to catalyze the
      reactions: 1) reduction of RAFT polymerized poly(2-(methacrylamido)
      glucopyranose) (PMAG), 2) converting protoporphyrin to protoporphyrinogen, 3)
      thiol-ene coupling reaction of PMAG and protoporphyrinogen. The product is
      oxidized in the same pot to generate the final porphyrin-PMAG conjugates. The
      resulting conjugates are characterized by NMR, GPC, UV-Vis, and fluorescence
      spectroscopy. Glycoparticles (~ 200 nm) bearing glucose units are formed by
      dissolving the conjugates in water. Glycoparticles show enhanced binding ability
      toward Con A, bind K562 cells efficiently and kill these cells under light
      irradiation in dose and light treatment length dependent manners, illustrating
      the potential biological applications of the conjugates as photosensitizer for
      cancer imaging and photodynamic therapy.

PMID- 24285578
TI  - Novel tubulin antagonist pretubulysin displays antivascular properties in vitro
      and in vivo.
AB  - OBJECTIVE: Pretubulysin (PT) is a novel, synthetically accessible myxobacterial
      compound that acts as a tubulin-depolymerizing agent and inhibits cancer cell
      growth in vitro and in vivo. Moreover, PT was found to attenuate tumor
      angiogenesis. Here, we hypothesized that PT could exert antivascular activities
      on existing tumor vessels. APPROACH AND RESULTS: We aimed to characterize the
      antivascular effects of PT and to elucidate the underlying mechanisms in
      endothelial cells. In vitro, PT rapidly induced endothelial hyperpermeability and
      a concentration-dependent disassembly of established endothelial tubes on
      Matrigel and in an ex vivo aortic ring model. It disrupted endothelial cell
      junctions and triggered F-actin stress fiber formation and cell contraction by
      the RhoA/Rho-associated protein kinase pathway without causing cell death. In
      vivo, using a hamster dorsal skinfold chamber preparation, PT significantly
      decreased blood flow and vessel diameter in hamster A-Mel-3 amelanotic melanoma
      tumors but not in the neighboring healthy tissue. In a second tumor model using
      mice with subcutaneous murine B16 melanoma tumors, a single dose of PT (10 mg/kg)
      caused a shut down of tumor blood flow and a strong central tumor cell necrosis
      within 24 hours. Repeated PT administration significantly decelerates tumor
      growth and seems to be well tolerated. CONCLUSIONS: In summary, we could show for
      the first time that the antitumor effect of PT is, at least in part, mediated via
      its antivascular activities on existing tumor vessels.

PMID- 24285579
TI  - Multiple-site activation of the cysteinyl leukotriene receptor 2 is required for
      exacerbation of ischemia/reperfusion injury.
AB  - OBJECTIVE: Transgenic overexpression of the human cysteinyl leukotriene receptor
      2 (CysLT2R) in murine endothelium exacerbates vascular permeability and
      ischemia/reperfusion injury. Here, we explore the underlying mechanisms of
      CysLT2R activation-mediated inflammation and delineate the relative contributions
      of endogenous murine CysLT2R and the transgene-derived receptor. APPROACH AND
      RESULTS: We created a novel mouse with only endothelial-expressed CysLT2R
      (endothelium-targeted overexpression mice [EC]/CysLT2R-knockout mice [KO]) by
      crossing EC with KO to dissect the role of endothelial CysLT2R in tissue injury.
      Surprisingly, we discovered that damage in EC/KO mice was not elevated (24%
      versus 47% EC) after ischemia/reperfusion. We examined vascular permeability and
      leukocyte recruitment/rolling responses in the cremaster vasculature after
      cysteinyl leukotriene (cysLT) stimulation. Mice possessing transgenic endothelial
      CysLT2R overexpression, whether EC or EC/KO, when stimulated with cysLTs,
      exhibited vascular hyperpermeability, declining leukocyte flux, and a transient
      increase in slow-rolling leukocyte fraction. Mice lacking endogenous CysLT2R
      (both KO [20 +/- 3 cells/min] EC/KO [24 +/- 3]) showed lower-rolling leukocyte
      flux versus wild-type (38 +/- 6) and EC (35 +/- 6) mice under unstimulated
      conditions. EC/KO mice differed from EC counterparts in that vascular
      hyperpermeability was not present in the absence of exogenous cysLTs.
      CONCLUSIONS: These results indicate that endothelial and nonendothelial CysLT2R
      niches have separate roles in mediating inflammatory responses. Endothelial
      receptor activation results in increased vascular permeability and leukocyte slow
      rolling, facilitating leukocyte transmigration. Nonendothelial receptors, likely
      located on resident/circulating leukocytes, facilitate endothelial receptor
      activation and leukocyte transit. Activation of both receptor populations is
      required for injury exacerbation.

PMID- 24285580
TI  - G-protein-coupled receptor 91 and succinate are key contributors in neonatal
      postcerebral hypoxia-ischemia recovery.
AB  - OBJECTIVE: Prompt post-hypoxia-ischemia (HI) revascularization has been suggested
      to improve outcome in adults and newborn subjects. Other than hypoxia-inducible
      factor, sensors of metabolic demand remain largely unknown. During HI, anaerobic
      respiration is arrested resulting in accumulation of carbohydrate metabolic
      intermediates. As such succinate readily increases, exerting its biological
      effects via a specific receptor, G-protein-coupled receptor (GPR) 91. We
      postulate that succinate/GPR91 enhances post-HI vascularization and reduces
      infarct size in a model of newborn HI brain injury. APPROACH AND RESULTS: The
      Rice-Vannucci model of neonatal HI was used. Succinate was measured by mass
      spectrometry, and microvascular density was evaluated by quantification of lectin
      stained cryosection. Gene expression was evaluated by real-time polymerase chain
      reaction. Succinate levels rapidly increased in the penumbral region of brain
      infarcts. GPR91 was foremost localized not only in neurons but also in
      astrocytes. Microvascular density increased at 96 hours after injury in wild-type
      animals; it was diminished in GPR91-null mice leading to an increased infarct
      size. Stimulation with succinate led to an increase in growth factors implicated
      in angiogenesis only in wild-type mice. To explain the mode of action of
      succinate/GPR91, we investigated the role of prostaglandin E2-prostaglandin E
      receptor 4, previously proposed in neural angiogenesis. Succinate-induced
      vascular endothelial growth factor expression was abrogated by a cyclooxygenase
      inhibitor and a selective prostaglandin E receptor 4 antagonist. This antagonist
      also abolished succinate-induced neovascularization. CONCLUSIONS: We uncover a
      dominant metabolic sensor responsible for post-HI neurovascular adaptation,
      notably succinate/GPR91, acting via prostaglandin E2-prostaglandin E receptor 4
      to govern expression of major angiogenic factors. We propose that pharmacological
      intervention targeting GPR91 could improve post-HI brain recovery.

PMID- 24285581
TI  - Changes in ultrasound-assessed carotid intima-media thickness and plaque with a
      Mediterranean diet: a substudy of the PREDIMED trial.
AB  - OBJECTIVE: The Prevencion con Dieta Mediterranea (PREDIMED) trial showed that a
      Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or
      30 g/d of mixed nuts reduced incident cardiovascular events compared with a
      control (low fat) diet. The mechanisms of cardiovascular protection afforded by
      MedDiets remain to be uncovered. We assessed the effect of both supplemented
      MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height,
      the ultrasound features that best predict future cardiovascular events, in
      subjects at high cardiovascular risk. APPROACH AND RESULTS: In a PREDIMED
      subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA,
      bifurcation, and common) were sonographically assessed at baseline and after
      intervention for a mean of 2.4 years. We evaluated 164 subjects with complete
      data. In a multivariate model, mean ICA-IMT progressed in the control diet group
      (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it
      regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024
      versus control). Similar results were observed for maximum ICA-IMT (control,
      0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm];
      P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm];
      MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in
      ICA-IMT or plaque after the MedDiet+extra virgin olive oil. CONCLUSIONS: Compared
      with a control diet, consumption of a MedDiet supplemented with nuts is
      associated with delayed progression of ICA-IMT and plaque. The results contribute
      mechanistic evidence for the reduction of cardiovascular events observed in the
      PREDIMED trial. CLINICAL TRIAL REGISTRATION URL: http://www.controlled
      trials.com. Unique identifier: ISRCTN35739639.

PMID- 24285582
TI  - Effect of niacin on high-density lipoprotein apolipoprotein A-I kinetics in
      statin-treated patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate the effect of extended-release (ER) niacin on the
      metabolism of high-density lipoprotein (HDL) apolipoprotein A-I (apoA-I) in men
      with type 2 diabetes mellitus on a background of optimal statin therapy. APPROACH
      AND RESULTS: Twelve men with type 2 diabetes mellitus were recruited for a
      randomized, crossover design trial. Patients were randomized to rosuvastatin or
      rosuvastatin plus ER niacin for 12 weeks and then crossed over to the alternate
      therapy after a 3-week washout period. Metabolic studies were performed at the
      end of each treatment period. HDL apoA-I kinetics were measured after a
      standardized liquid mixed meal and a bolus injection of d3-leucine for 96 hours.
      Compartmental analysis was used to model the data. ER niacin significantly
      decreased plasma triglyceride, plasma cholesterol, non-HDL cholesterol, low
      density lipoprotein cholesterol, and apoB (all P<0.05) and significantly
      increased HDL cholesterol and apoA-I concentrations (P<0.005 and P<0.05,
      respectively). ER niacin also significantly increased HDL apoA-I pool size (6,088
      +/- 292 versus 5,675 +/- 305 mg; P<0.001), and this was attributed to a lower HDL
      apoA-I fractional catabolic rate (0.33 +/- 0.01 versus 0.37 +/- 0.02 pools/d;
      P<0.005), with no significant changes in HDL apoA-I production (20.93 +/- 0.63
      versus 21.72 +/- 0.85 mg/kg per day; P=0.28). CONCLUSIONS: ER niacin increases
      HDL apoA-I concentration in statin-treated subjects with type 2 diabetes mellitus
      by lowering apoA-I fractional catabolic rate. The effect on HDL metabolism was
      independent of the reduction in plasma triglyceride with ER niacin treatment.
      Whether this finding applies to other dyslipidemic populations remains to be
      investigated.

PMID- 24285583
TI  - A randomized controlled trial of a correspondence-based intervention for carers
      of relatives with psychosis.
AB  - BACKGROUND: Family members play a crucial role in supporting the recovery of
      loved ones with psychosis. The journey of recovery is not only traversed by the
      person experiencing the mental illness but also by their family. Interventions to
      support these families have traditionally either focused on psychoeducation or
      addressed problematic interactions or expressed emotion. Family programmes have
      far less frequently emphasized supporting family members' adjustment to the
      challenges posed by their relative's disorder or their recovery from associated
      distress. The study compared a control condition that received only a
      psychoeducational booklet (Information) and a condition also receiving a
      correspondence-based interactive recovery-oriented intervention (Connections).
      The Connections group was expected to show greater improvements in recovery
      knowledge, well-being, experiences of caregiving, hopefulness and distress.
      METHOD: A randomized controlled trial was conducted to evaluate the effectiveness
      of two correspondence-based family interventions delivered to 81 carers of
      relatives with psychosis. RESULTS: Intent-to-treat analyses showed no
      differential outcomes between conditions, but an analysis of participants who
      substantially completed their allocated treatment showed that carers receiving
      Connections had significantly more improvements in well-being, positive
      experiences of caregiving and distress. CONCLUSIONS: Correspondence interventions
      that support carer's recovery may result in more positive mental health for those
      who complete key elements of the programme compared with information alone.
      However, many carers do not complete a correspondence programme and this may
      limit its impact.

PMID- 24285584
TI  - Inhibition of hypoxia-induced gene transcription by substituted pyrazolyl
      oxadiazoles: initial lead generation and structure-activity relationships.
AB  - The transcription factors hypoxia-inducible factor-1 and -2 (HIF-1 and HIF-2)
      orchestrate a multitude of processes that allow tumor cells to survive under
      conditions of low oxygen and nutrients, and that lead to resistance to some
      apoptotic pathways and facilitate invasion and metastasis. Therefore, inhibition
      of transactivation by HIF has become an attractive target in cancer research.
      Herein we present the results of a cell-based screening approach that led to the
      discovery of substituted 1H-pyrazole-3-carboxamides. Chemical optimization of the
      hit class with respect to potency and metabolic stability is described; it
      resulted in novel 5-(1H-pyrazol-3-yl)-1,2,4-oxadiazoles that inhibit the hypoxia
      induced accumulation of HIF-1alpha and HIF-2alpha. The HIF inhibitory potency in
      the screening cell system was improved from IC50 190 to 0.7 nM, and significant
      parts of the SAR are disclosed. For a key compound, the ability to suppress the
      hypoxia-induced expression of HIF target genes was studied in A549 human lung
      adenocarcinoma cells. The same compound shows a favorable pharmacokinetic profile
      in rats after i.v. and p.o. administration.

PMID- 24285585
TI  - An automated hand-held elastometer for quantifying the passive stiffness of the
      levator ani muscle in women.
AB  - AIM: Design and develop an automated, hand-held instrument (elastometer) to
      assess in vivo passive stiffness of the pelvic floor muscle. MATERIALS AND
      METHODS: The elastometer system consisted of a hand piece, real-time controller,
      and laptop computer. A cable connected the hand-piece to the controller, which
      communicated with a laptop computer via an ethernet connection. Force sensitivity
      calibration and displacement accuracy were determined experimentally using a
      spring load and an Instron mechanical tester. A test re-test series quantified
      the in vivo repeatability (within a procedure) and reproducibility (between
      procedures after a 5 min delay) of passive stiffness in volunteers (n = 20).
      Stiffness was determined from the gradient of the force-displacement curve for
      each cycle. RESULTS: The force-aperture spring measurements from the elastometer
      showed consistent (r(2) = 1.0000) agreement with those measured by the Instron.
      The difference between spring stiffness as measured by the elastometer and the
      Instron (388.1 N/m cf. 388.5 N/m, respectively) was negligible. The intra-class
      correlation coefficient for repeatability within procedures was 0.986 95% CI
      (0.964-0.994) n = 20, and reproducibility between procedures ICC 0.934 (95% CI
      0.779-0.981) n = 12. Bland-Altman analysis determined a bias of 0.3 and 18.5 N/m,
      for repeatability and reproducibility respectively. Neither bias is likely to be
      clinically significance. CONCLUSION: The elastometer demonstrated very good
      repeatability and accuracy in the measurement of force/displacement during in
      vitro testing. There was a high degree of repeatability and reproducibility in
      stiffness measurements in a test re-test series. Our results demonstrate the
      elastometer is accurate and reliable and thereby suitable for larger clinical
      trials.

PMID- 24285586
TI  - FDA perspective on the need for revised performance goals for evaluating stenting
      of femoropopliteal arteries.

PMID- 24285587
TI  - Metal-organic frameworks reactivate deceased diatoms to be efficient CO(2)
      absorbents.
AB  - Diatomite combined with certain metal-organic frameworks (MOFs) is shown to be an
      effective CO2 absorbent, although diatomite alone is regarded as inert with
      respect to CO2 absorption. This finding opens the prospect of reactivating
      millions of tons of diatomite for CO2 absorption. It also shows for the first
      time that diatom frustules can act as CO2 buffers, an important link in a
      successive biological CO2 concentration mechanism chain that impacts on global
      warming. 

PMID- 24285588
TI  - Peptide ligation chemistry at selenol amino acids.
AB  - The convergent assembly of peptide fragments by native chemical ligation has
      revolutionized the way in which proteins can be accessed by chemical synthesis. A
      variation of native chemical ligation involves the reaction of peptides bearing
      an N-terminal selenocysteine residue with peptide thioesters, which proceeds
      through the same mechanism as the parent reaction. This transformation was first
      investigated in 2001 for the installation of selenocysteine into peptides and
      proteins via ligation chemistry. The recent discovery that selenocysteine
      residues within peptides can be chemoselectively deselenized without the
      concomitant desulfurization of cysteine residues has led to renewed interest in
      ligation chemistry at selenocysteine. This review outlines the use of
      selenocysteine in ligation chemistry as well as recent investigations of
      chemoselective ligation-deselenization chemistry at other selenol-derived amino
      acids that have the potential to greatly expand the number of targets that can be
      accessed by chemical synthesis.

PMID- 24285589
TI  - A rat tail temporary static compression model reproduces different stages of
      intervertebral disc degeneration with decreased notochordal cell phenotype.
AB  - The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct
      cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In
      human discs, NCs are lost during adolescence, which is also when discs begin to
      show degenerative signs. However, little evidence exists regarding the link
      between NC disappearance and the pathogenesis of disc degeneration. To clarify
      this, a rat tail disc degeneration model induced by static compression at 1.3 MPa
      for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days.
      Radiography, MRI, and histomorphology showed degenerative disc findings in
      response to the compression period. Immunofluorescence displayed that the number
      of DAPI-positive NP cells decreased with compression; particularly, the decrease
      was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive
      cells, identified as NCs. The proportion of TUNEL-positive cells, which
      predominantly comprised non-NCs, increased with compression. Quantitative PCR
      demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group
      and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2alpha-1 mRNA
      levels were down-regulated in both groups. This rat tail temporary static
      compression model, which exhibits decreased NC phenotype, increased apoptotic
      cell death, and imbalanced catabolic and anabolic gene expression, reproduces
      different stages of intervertebral disc degeneration.

PMID- 24285590
TI  - Discovery of potent HDAC inhibitors based on chlamydocin with inhibitory effects
      on cell migration.
AB  - The histone deacetylase (HDAC) family is a promising drug target class owing to
      the importance of these enzymes in a variety of cellular processes. Docking
      studies were conducted to identify novel HDAC inhibitors. Subtle modifications in
      the recognition domain were introduced into a series of chlamydocin analogues,
      and the resulting scaffolds were combined with various zinc binding domains.
      Remarkably, cyclo(L-Asu(NHOH)-L-A3mc6c-L-Phe-D-Pro, compound 1 b), with a methyl
      group at positions 3 or 5 on the aliphatic ring, exhibited better
      antiproliferative effects than trichostatin A (TSA) against MCF-7 and K562 cell
      lines. In addition to cell-cycle arrest and apoptosis, cell migration inhibition
      was observed in cells treated with compound 1 b. Subsequent western blot analysis
      revealed that the balance between matrix metalloproteinase 2 (MMP2) and tissue
      inhibitors of metalloproteinase 1 (TIMP1) determines the degree of
      metalloproteinase activity in MCF-7 cells, thereby regulating cell migration. The
      improved inhibitory activity imparted by altering the hydrophobic substitution
      pattern at the bulky cap group is a valuable approach in the development of novel
      HDAC inhibitors. 

PMID- 24285591
TI  - Rapidly cleaving bovine two-cell embryos have better developmental potential and
      a distinctive mRNA pattern.
AB  - Mammalian embryos that rapidly reach the two-cell stage in culture have a higher
      probability of becoming viable blastocysts. Our goal was to separate two-cell
      bovine embryos based on their zygotic cleavage timing, and to assess their global
      mRNA levels. Following in vitro fertilization, all embryos that cleaved by 29.5
      hpi (early) were cultured separately from those that divided at 46 hpi (late).
      The blastocyst rates were 46.1 +/- 3.7% and 6.1 +/- 3.4% for early- and late
      cleavers, respectively (P < 0.01). Seven replicates of selected two-cell embryos
      were collected at each time point for microarray characterization (n = 4) and
      quantitative reverse-transcriptase PCR (n = 3); the rest were left in culture for
      blastocyst evaluation. A total of 774 and 594 probes were preferentially present
      in early- and late-cleaving embryos, respectively (fold change +/- 1.5, P <
      0.05), with important contrasts related to cell cycle, gene expression, RNA
      processing, and protein degradation functions. A total of 12 transcripts were
      assessed by quantitative PCR, of which ATM, ATR, CTNNB1, MSH6, MRE11A, PCNA, APC,
      CENPE, and GRB2 were in agreement with the hybridization results. Since most of
      these molecules are directly or indirectly associated with cell-cycle regulation,
      DNA damage response, and transcription control, our results strongly suggest key
      roles for those biological functions in mammalian preimplantation development.

PMID- 24285592
TI  - Percutaneous retrieval of a twisted guide catheter using a longer second radial
      sheath.
AB  - Coronary angiography and percutaneous coronary intervention (PCI) over the radial
      approach are becoming more frequent and are recommended by the European
      Association of Percutaneous Cardiovascular Interventions and European Society of
      Cardiology. The radial approach leads to less bleeding and improved survival in
      ST-segment elevation myocardial infarction. Pronounced guide catheter
      manipulation in cases with tortuous access routes and requirement of extra backup
      during complex PCI may structurally damage the guide shaft and facilitate
      twisting and bending. We present three cases where a twisted coronary catheter
      became stuck in the radial artery and describe a minimally invasive retrieval
      technique using a second introducer sheath of same French (F) size and greater
      length.

PMID- 24285593
TI  - Slice accelerated gradient-echo spin-echo dynamic susceptibility contrast imaging
      with blipped CAIPI for increased slice coverage.
AB  - PURPOSE: To improve slice coverage of gradient echo spin echo (GESE) sequences
      for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice
      (SMS) method. METHODS: Data were acquired on 3 Tesla (T) MR scanners with a 32
      channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two
      fold slice coverage and same temporal sampling was compared with a standard GESE
      sequence, both with 2* in-plane acceleration. A signal to noise ratio (SNR)
      comparison was performed on one healthy subject. Additionally, data with
      Gadolinium injection were collected on three patients with glioblastoma using
      both sequences, and perfusion analysis was performed on healthy tissues as well
      as on tumor. RESULTS: Retained SNR of SMS DSC is 90% for a gradient echo (GE) and
      99% for a spin echo (SE) acquisition, compared with a standard acquisition
      without slice acceleration. Comparing cerebral blood volume maps, it was observed
      that the results of standard and SMS acquisitions are comparable for both GE and
      SE images. CONCLUSION: Two-fold slice accelerated DSC MRI achieves similar SNR
      and perfusion metrics as a standard acquisition, while allowing a significant
      increase in slice coverage of the brain. The results also point to a possibility
      to improve temporal sampling rate, while retaining the same slice coverage.

PMID- 24285594
TI  - Initial experience with the Glidesheath Slender for transradial coronary
      angiography and intervention: a feasibility study with prospective radial
      ultrasound follow-up.
AB  - OBJECTIVE: The aim of this study is to evaluate the feasibility and safety of the
      Glidesheath Slender in routine transradial (TR) coronary angiography and
      intervention. BACKGROUND: In recent years, The TR approach has gained in
      popularity because of several advantages such as reduced vascular access site
      complications and immediate patient mobilization. Procedural success has been
      further improved through technological innovations and the development of less
      invasive devices. The Glidesheath Slender (Terumo, Tokyo, Japan) is a new
      dedicated radial sheath with a thinner wall and hydrophilic coating. It combines
      an inner diameter compatible with 6Fr guiding catheter with an outer diameter
      close to current 5Fr sheaths. Its use has the potential to decrease invasiveness
      and access site complications during TR procedures. METHODS: A total of 114
      consecutive patients undergoing TR coronary angiography and/or PCI using the
      Gidesheath Slender were included in a prospective single-center feasibility and
      safety study. RESULTS: Procedural success was 99.1% with only one case requiring
      conversion to femoral access. There were six minor hematomas but none of the
      patients experienced major vascular complications. The rate of symptomatic radial
      spasm was 4.4%. No case of major sheath kinking was noted. Doppler ultrasound
      examination of the radial artery at 1 month follow-up was available in 113/114
      patients with only one case of radial artery occlusion (RAO) (0.88%).
      CONCLUSIONS: Routine use of the Glidesheath Slender for TR coronary angiography
      and interventions is safe and feasible with a high rate of procedural success and
      a low rate of RAO. (c) 2013 Wiley Periodicals, Inc.

PMID- 24285595
TI  - Influence of different levels of immersion in water on the pulmonary function and
      respiratory muscle pressure in healthy individuals: observational study.
AB  - BACKGROUND AND PURPOSE: Immersion in water, with the head above the water line,
      causes acute physiological changes in the pulmonary and cardiovascular systems.
      The aim of this study was to evaluate the acute physiological responses to
      immersion on lung volumes and respiratory muscle strength at different depths.
      METHODS: A cross-sectional study was conducted in 28 healthy individuals (21.75
      +/- 1.99 years; 13 men and 15 women). Anthropometric and spirometric data as well
      as respiratory muscle strength were evaluated. Evaluations were carried out on
      dry land (DL) and in a pool at three different levels of immersion: iliac crests
      (IC), xiphoid appendix of the sternum (XA) and clavicles (CL). The order of
      evaluation for spirometry and maximal inspiratory and expiratory pressures
      between DL and the different levels of immersion was randomized. The ANOVA test
      for repeated measures with post hoc Tukey was applied to compare the variables.
      RESULTS: Vital capacity exhibited lower values at the CL level compared with DL,
      XA and IC (p < 0.01). The most significant change in forced expiratory volume in
      the first second (FEV(1)) occurred under immersion at CL and XA levels. No
      differences in maximal expiratory pressure were found in the comparisons between
      the different levels of immersion and DL (p = 0.19). There was nevertheless a
      decrease in maximum inspiratory pressure with immersion at the CL level (91 +/-
      23 cmH(2)O) compared with DL (105 +/- 29 cmH(2)O), XA (99 +/- 24 cmH(2)O) and IC
      (101 +/- 25 cmH(2)O) values (p < 0.01). CONCLUSION: The results suggest that
      immersion at the level of the clavicles and xiphoid appendix alters lung function
      and respiratory muscle strength when compared with the values measured out of the
      water and immersed at the IC level in healthy individuals, demonstrating the
      influence of hydrostatic pressure on the respiratory system.

PMID- 24285596
TI  - The fight against the influenza A virus H1N1: synthesis, molecular modeling, and
      biological evaluation of benzofurazan derivatives as viral RNA polymerase
      inhibitors.
AB  - The influenza RNA polymerase complex, which consists of the three subunits PA,
      PB1, and PB2, is a promising target for the development of new antiviral drugs. A
      large library of benzofurazan compounds was synthesized and assayed against
      influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by
      inhibiting the viral RNA polymerase complex through disruption of the complex
      formed between subunits PA and PB1. Docking studies were also performed to
      elucidate the binding mode of benzofurazans within the PB1 binding site in PA and
      to identify amino acids involved in their mechanism of action. The predicted
      binding pose is fully consistent with the biological data and lays the foundation
      for the rational development of more effective PA-PB1 inhibitors. 

PMID- 24285597
TI  - Carbonized eggshell membrane as a natural polysulfide reservoir for highly
      reversible Li-S batteries.
AB  - Carbonized sucrose-coated eggshell membranes (CSEMs) consisting of natural
      micropores function well as a polysulfide reservoir in Li/dissolved polysulfide
      cells. The bottom CSEM current collector encapsulates the active material, while
      the upper CSEM inhibitor intercepts the migrating polysulfides. This design with
      CSEM allows the dissolved polysulfides to be localized and the electrochemical
      reactions within the cathode region to be stabilized, resulting in high discharge
      capacity, long-term cycle stability, and high sulfur loading. 

PMID- 24285598
TI  - Preventing congenital syphilis - a regional audit of syphilis in pregnant women
      seen in Genitourinary Medicine services.
AB  - Genitourinary case records of 42 pregnant women with syphilis were reviewed as
      part of a regional audit following the re-emergence of congenital syphilis in the
      north east of England. National standards, from the British Association of Sexual
      Health and HIV guidelines on managing syphilis in pregnancy, were met in the
      majority of cases with 69% being treated according to national guidance and all
      cases completing treatment. Locally developed standards on multidisciplinary
      working and communication were met less well, with particular issues regarding
      the documentation of pregnancy outcomes in GUM records and communication between
      specialities being highlighted. A regional good practice guide has been developed
      and implemented to address standards not met, reduce adverse outcomes and prevent
      future cases of congenital syphilis. 

PMID- 24285599
TI  - Effects of fish oil on lipid profile and other metabolic outcomes in HIV-infected
      patients on antiretroviral therapy: a randomized placebo-controlled trial.
AB  - Although antiretroviral therapy has revolutionized the care of HIV-infected
      patients, it has been associated with metabolic abnormalities. Hence, this study
      was planned to investigate the effects of fish oil on lipid profile, insulin
      resistance, and body fat distribution in HIV-infected Brazilian patients on
      antiretroviral therapy, considering that marine omega-3 fatty acids seem to
      improve features of the metabolic syndrome. We conducted a randomized, parallel,
      placebo-controlled trial that assessed the effects of 3 g fish oil/day (540 mg of
      eicosapentaenoic acid plus 360 mg of docosahexaenoic acid) or 3 g soy oil/day
      (placebo) on 83 HIV-infected Brazilian men and non-pregnant women on
      antiretroviral therapy. No statistically significant relationships between fish
      oil supplementation and longitudinal changes in triglyceride (p = 0.335), low
      density lipoprotein cholesterol (p = 0.078), high-density lipoprotein cholesterol
      (p = 0.383), total cholesterol (p = 0.072), apolipoprotein B (p = 0.522),
      apolipoprotein A1 (p = 0.420), low-density lipoprotein cholesterol/apolipoprotein
      B ratio (p = 0.107), homeostasis model assessment for insulin resistance index (p
      = 0.387), body mass index (p = 0.068), waist circumference (p = 0.128), and
      waist/hip ratio (p = 0.359) were observed. A low dose of fish oil did not alter
      lipid profile, insulin resistance, and body fat distribution in HIV-infected
      patients on antiretroviral therapy. 

PMID- 24285601
TI  - 2013 UK national guideline for consultations requiring sexual history taking.
      Clinical Effectiveness Group British Association for Sexual Health and HIV.

PMID- 24285600
TI  - Prevalence of syphilis infection and associations with sexual risk behaviours
      among HIV-positive men who have sex with men in Shanghai, China.
AB  - The aims of this study were to understand the prevalence and correlates of
      syphilis infection among HIV-positive men who have sex with men (MSM) in
      Shanghai, China. A total of 200 HIV-positive MSM participants were recruited
      using "snowball" sampling. Participants were tested for syphilis and completed a
      one-time questionnaire which included demographic characteristics, sexual
      behaviours with male and female sexual partners, substance use, and use of
      antiretroviral medications. Prevalence of syphilis infection was 16.5%. Among
      HIV/syphilis co-infected participants, 63.6% reported having anal sex with male
      partners and 24.2% did not use condoms consistently during the past six months;
      66.7% reported having oral sex with male partners and 51.5% reported unprotected
      oral sex during the past six months. Factors associated with testing seropositive
      for syphilis infection included receptive anal sex with a male partner in the
      past six months (AOR = 12.61, 90% CI = 2.38-66.89), illicit drug use in the past
      six months (AOR = 11.47, 90% CI = 2.47-53.45), and use of antiretroviral
      medication (AOR = 4.48, 90% CI = 1.43-14.05). These data indicate a need for
      "positive prevention" interventions targeting HIV-positive MSM in China.

PMID- 24285602
TI  - DDGni: dynamic delay gene-network inference from high-temporal data using gapped
      local alignment.
AB  - MOTIVATION: Inferring gene-regulatory networks is very crucial in decoding
      various complex mechanisms in biological systems. Synthesis of a fully functional
      transcriptional factor/protein from DNA involves series of reactions, leading to
      a delay in gene regulation. The complexity increases with the dynamic delay
      induced by other small molecules involved in gene regulation, and noisy cellular
      environment. The dynamic delay in gene regulation is quite evident in high
      temporal live cell lineage-imaging data. Although a number of gene-network
      inference methods are proposed, most of them ignore the associated dynamic time
      delay. RESULTS: Here, we propose DDGni (dynamic delay gene-network inference), a
      novel gene-network-inference algorithm based on the gapped local alignment of
      gene-expression profiles. The local alignment can detect short-term gene
      regulations, that are usually overlooked by traditional correlation and mutual
      Information based methods. DDGni uses 'gaps' to handle the dynamic delay and non
      uniform sampling frequency in high-temporal data, like live cell imaging data.
      Our algorithm is evaluated on synthetic and yeast cell cycle data, and
      Caenorhabditis elegans live cell imaging data against other prominent methods.
      The area under the curve of our method is significantly higher when compared to
      other methods on all three datasets. AVAILABILITY: The program, datasets and
      supplementary files are available at http://www.jjwanglab.org/DDGni/.

PMID- 24285603
TI  - Fat signal suppression for coronary MRA at 3T using a water-selective adiabatic
      T2 -preparation technique.
AB  - PURPOSE: To improve fat saturation in coronary MRA at 3T by using a spectrally
      selective adiabatic T2 -Prep (WSA-T2 -Prep). METHODS: A conventional adiabatic T2
      -Prep (CA-T2 -Prep) was modified, such that the excitation and restoration pulses
      were of differing bandwidths. On-resonance spins are T2 -Prepared, whereas off
      resonance spins, such as fat, are spoiled. This approach was combined with a
      CHEmically Selective Saturation (CHESS) pulse to achieve even greater fat
      suppression. Numerical simulations were followed by phantom validation and in
      vivo coronary MRA. RESULTS: Numerical simulations demonstrated that augmenting a
      CHESS pulse with a WSA-T2 -Prep improved robustness to B1 inhomogeneities and
      that this combined fat suppression was effective over a broader spectral range
      than that of a CHESS pulse in a conventional T2 -Prepared sequence. Phantom
      studies also demonstrated that the WSA-T2 -Prep+CHESS combination produced
      greater fat suppression across a range of B1 values than did a CA-T2 -Prep+CHESS
      combination. Lastly, in vivo measurements demonstrated that the contrast-to-noise
      ratio between blood and myocardium was not adversely affected by using a WSA-T2 
      Prep, despite the improved abdominal and epicardial fat suppression.
      Additionally, vessel sharpness improved. CONCLUSION: The proposed WSA-T2 -Prep
      method was shown to improve fat suppression and vessel sharpness as compared to a
      CA-T2 -Prep technique, and to also increase fat suppression when combined with a
      CHESS pulse.

PMID- 24285604
TI  - Nonheme iron mediated oxidation of light alkanes with oxone: characterization of
      reactive oxoiron(IV) ligand cation radical intermediates by spectroscopic studies
      and DFT calculations.
AB  - The oxidation of light alkanes that is catalyzed by heme and nonheme iron enzymes
      is widely proposed to involve highly reactive {Fe(V)=O} species or {Fe(IV)=O}
      ligand cation radicals. The identification of these high-valent iron species and
      the development of an iron-catalyzed oxidation of light alkanes under mild
      conditions are of vital importance. Herein, a combination of tridentate and
      bidentate ligands was used for the generation of highly reactive nonheme {Fe=O}
      species. A method that employs [Fe(III)(Me3tacn)(Cl-acac)Cl](+) as a catalyst in
      the presence of oxone was developed for the oxidation of hydrocarbons, including
      cyclohexane, propane, and ethane (Me3tacn=1,4,7-trimethyl-1,4,7
      triazacyclononane; Cl-acac=3-chloro-acetylacetonate). The complex
      [Fe(III)(Tp)2](+) and oxone enabled stoichiometric oxidation of propane and
      ethane. ESI-MS, EPR and UV/Vis spectroscopy, (18)O labeling experiments, and DFT
      studies point to [Fe(IV)(Me3tacn)({Cl-acac}(.+))(O)](2+) as the catalytically
      active species.

PMID- 24285606
TI  - Second messenger networks for accurate growth cone guidance.
AB  - Growth cones are able to navigate over long distances to find their appropriate
      target by following guidance cues that are often presented to them in the form of
      an extracellular gradient. These external cues are converted into gradients of
      specific signaling molecules inside growth cones, while at the same time these
      internal signals are amplified. The amplified instruction is then used to
      generate asymmetric changes in the growth cone turning machinery so that one side
      of the growth cone migrates at a rate faster than the other side, and thus the
      growth cone turns toward or away from the external cue. This review examines how
      signal specification and amplification can be achieved inside the growth cone by
      multiple second messenger signaling pathways activated downstream of guidance
      cues. These include the calcium ion, cyclic nucleotide, and phosphatidylinositol
      signaling pathways.

PMID- 24285605
TI  - Early outcomes of alcohol septal ablation for hypertrophic obstructive
      cardiomyopathy: a European multicenter and multinational study.
AB  - BACKGROUND: This study was designed to evaluate the outcomes of alcohol septal
      ablation (ASA) under multicenter and multinational conditions. METHODS: Data for
      459 patients (age 57 +/- 13 years) from nine European centers were prospectively
      collected and retrospectively analyzed. RESULTS: ASA led to a significant
      reduction in outflow gradient (PG) and dyspnea [median of PG from 88 (58-123) mm
      Hg to 21 (11-41) mm Hg; median of NYHA class from 3 (2-3) to 1 (1-2); P < 0.01].
      The incidence of 3-month major adverse events (death, electrical cardioversion
      for tachyarrhythmias, resuscitation) and mortality was 2.8% and 0.7%,
      respectively. Permanent pacemakers for post-ASA complete heart block were
      implanted in 43 patients (9%). Multivariate analysis identified higher amount of
      alcohol (however, in generally low-dose procedures), higher baseline left
      ventricular ejection fraction and higher age as independent predictors of PG
      decrease >=50%. CONCLUSIONS: The results of the first European multicenter and
      multinational study demonstrate that real-world early outcomes of ASA patients
      are better than was reported in observations from the first decade after ASA
      introduction.

PMID- 24285607
TI  - Rational design of boradiazaindacene (BODIPY)-based functional molecules.
AB  - Three boradiazaindacene (BODIPY) dyes with different-coloured (greenish-yellow,
      orange and red) fluorescence and good Stokes shifts were synthesised starting
      from the greenish-yellow BODIPY dye PM546. The high Stokes shifts of the dyes are
      due to the release of the steric strain in their excited states relative to that
      in the highly twisted ground states. One of these compounds might be a useful
      water-soluble fluorophore, whereas the other two are promising H(+) sensors. 

PMID- 24285608
TI  - Different anesthesia regimes modulate the functional connectivity outcome in
      mice.
AB  - PURPOSE: The use of resting-state functional MRI (rsfMRI) in preclinical research
      is expanding progressively, with the majority of resting-state imaging performed
      in anesthetized animals. Since anesthesia may change the physiology and, in
      particular, the neuronal activity of an animal considerably, it may also affect
      rsfMRI findings. Therefore, this study compared rsfMRI data from awake mice with
      rsfMRI results obtained from mice anesthetized with alpha-chloralose (120 mg/kg),
      urethane (2.5 g/kg), or isoflurane (1%). METHODS: Functional connectivity (FC)
      was estimated using both independent component analysis (40 components) and ROI
      based analysis to zoom in on the effect of different anesthetics on inter
      hemispheric FC. RESULTS: The data revealed an important diminishment of cortical
      interhemispheric FC in both the alpha-chloralose and urethane groups in
      comparison with the isoflurane and awake groups. CONCLUSION: When performing FC
      analysis in anesthetized mice, the impact of anesthetics must be taken into
      account. The required doses for stable anesthesia during MRI significantly
      decrease interhemispheric FC.

PMID- 24285609
TI  - The effect of di-n-butyl phthalate on testis and the potential protective effects
      of resveratrol.
AB  - This study aimed to observe the possible protective effects of resveratrol (RSV)
      against the damage of di-n-butyl phthalate (DBP) on the testis. The study was
      conducted in 6 groups of rats with 6 animals in each group aged 20 days. The
      groups include group 1: control group; group 2: solvent (carboxymethylcellulose
      (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20
      mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20
      mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect
      immunohistochemical staining was performed with c-kit, AT1, and ER-alpha
      antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It
      was found in the DBP-applied groups the C-kit immunostaining, which is parallel
      to increasing dose, decreased in comparison with the control. C-kit reactivity
      was similar to that of the control group in the group applied with 500 mg/kg/day
      + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied
      group. It was observed that the reactivity of AT1 increased in the DBP-applied
      groups. RSV reversed these changes with its protective effects. While there was
      not much difference between the groups in terms of estrogen receptor reactivity,
      it was observed that the high dose of DBP reduced the level of estrogen receptor
      and the resveratrol was not at enough levels in all doses. In TUNEL analysis,
      high doses of DBP increased the apoptosis in all types of cells; nevertheless,
      the resveratrol application decreased the apoptosis in the low-level DBP dose. In
      the statistical analysis, while the length of epithelium and the diameter of
      seminiferous tubules decreased for all the other groups, it reverted to its
      original state in the RSV-applied groups. In conclusion, DBP (with increasing
      dose) administration caused cycle and hormonal changes in testis, resveratrol
      were recovered the cyclic changes but in hormonal changes, RSV is efficient too
      but inadequate. 

PMID- 24285610
TI  - Chance and necessity: my encounter with gold catalysts.
AB  - "Have you tried gold?" This question after a presentation on hydrogen oxidation
      steered Masatake Haruta's research on heterogeneous catalysis. He found that gold
      combined with 3d transition metal oxides could exhibit surprisingly high
      catalytic activity for carbon monoxide oxidation at temperatures as low as 203 K.

PMID- 24285612
TI  - Highly sensitive and selective detection of nitrophenolic explosives by using
      nanospheres of a tetraphenylethylene macrocycle displaying aggregation-induced
      emission.
AB  - A tetraphenylethylene (TPE) Schiff-base macrocycle showing an aggregation-induced
      emission (AIE) effect has been synthesized, which could aggregate into
      nanospheres and emit yellow fluorescence in aqueous media. By virtue of its AIE
      effect, the macrocycle showed a sensitive and selective response to 2,4,6
      trinitrophenol (TNP) and 2,4-dinitrophenol (DNP) among a number of nitroaromatic
      compounds, which could be used to detect TNP and DNP at nanomolar levels.
      Moreover, it exhibited a superamplified quenching effect with DNP but not with
      TNP, providing a possible means of discriminating these two compounds. In
      comparison with open-chain TPE Schiff-bases, the cavity of the macrocycle is
      essential for the selectivity for DNP over TNP. In addition, quantitative
      analyses of both DNP and TNP in real water samples and qualitative detection of
      these two analytes in the solid state by the macrocycle have been tested. The
      reliability of the quantitative analysis has been confirmed by HPLC. Our findings
      demonstrate that the TPE Schiff-base macrocycle has great potential as an
      excellent sensor for DNP and TNP. 

PMID- 24285611
TI  - Identification of liver transplant candidates with hepatocellular carcinoma and a
      very low dropout risk: implications for the current organ allocation policy.
AB  - It has been shown that patients with hepatocellular carcinoma (HCC) meeting the
      United Network for Organ Sharing T2 (Milan) criteria have an advantage in
      comparison with patients without HCC under the current organ allocation system
      for liver transplantation (LT). We hypothesized that within the T2 HCC group,
      there is a subgroup with a low risk of wait-list dropout that should not receive
      the same listing priority. This study evaluated 398 consecutive patients with T2
      HCC listed for LT with a Model for End-Stage Liver Disease exception from March
      2005 to January 2011 at our center. Competing risk (CR) regression was used to
      determine predictors of dropout. The probabilities of dropout due to tumor
      progression or death without LT according to the CR analysis were 9.4% at 6
      months and 19.6% at 12 months. The median time from listing to LT was 8.8 months,
      and the median time from listing to dropout or death without LT was 7.2 months.
      Significant predictors of dropout or death without LT according to a multivariate
      CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2
      or 3 tumors, a lack of a complete response to the first locoregional therapy
      (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup
      (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response
      after the first LRT, and an AFP level <= 20 ng/mL after the first LRT) had 1- and
      2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the
      probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In
      conclusion, a combination of tumor characteristics and a complete response to the
      first LRT define a subgroup of patients with a very low risk of wait-list dropout
      who do not require the same listing priority. Our results may have important
      implications for the organ allocation policy for HCC.

PMID- 24285613
TI  - Annual banned-substance review: analytical approaches in human sports drug
      testing.
AB  - Monitoring the misuse of drugs and the abuse of substances and methods
      potentially or evidently improving athletic performance by analytical chemistry
      strategies is one of the main pillars of modern anti-doping efforts. Owing to the
      continuously growing knowledge in medicine, pharmacology, and (bio)chemistry, new
      chemical entities are frequently established and developed, various of which
      present a temptation for sportsmen and women due to assumed/attributed beneficial
      effects of such substances and preparations on, for example, endurance, strength,
      and regeneration. By means of new technologies, expanded existing test protocols,
      new insights into metabolism, distribution, and elimination of compounds
      prohibited by the World Anti-Doping Agency (WADA), analytical assays have been
      further improved in agreement with the content of the 2013 Prohibited List. In
      this annual banned-substance review, literature concerning human sports drug
      testing that was published between October 2012 and September 2013 is summarized
      and reviewed with particular emphasis on analytical approaches and their
      contribution to enhanced doping controls.

PMID- 24285614
TI  - Hypoxic locomotor rehabilitation for incomplete spinal cord injury: not an
      oxymoron.

PMID- 24285615
TI  - Injury to a specific neural pathway detected by ultra-high-field MRI.

PMID- 24285616
TI  - White matter perivascular spaces: an MRI marker in pathology-proven cerebral
      amyloid angiopathy?
AB  - OBJECTIVE: We investigated whether severe, MRI-visible perivascular spaces (PVS)
      in the cerebral hemisphere white matter (centrum semiovale) are more common in
      patients with pathology-proven cerebral amyloid angiopathy (CAA) than in those
      with pathology-proven non-CAA-related intracerebral hemorrhage (ICH). METHODS:
      Using a validated 4-point scale on axial T2-weighted MRI, we compared PVS in
      patients with pathology-proven CAA to PVS in those with spontaneous ICH but no
      histopathologic evidence of CAA. In a preliminary analysis restricted to patients
      with T2*-weighted gradient-recalled echo MRI, we also investigated whether
      including severe centrum semiovale PVS increases the sensitivity of existing
      diagnostic criteria for probable CAA. RESULTS: Fourteen patients with CAA and 10
      patients with non-CAA-related ICH were included. Eight of the patients with CAA
      were admitted for symptomatic, spontaneous lobar ICH, 1 because of ischemic
      stroke, 1 with transient focal neurologic episodes, and 4 due to cognitive
      decline. Severe (>20) centrum semiovale PVS were more frequent in patients with
      CAA compared to controls (12/14 [85.7%; 95% confidence interval (CI): 57.2%
      98.2%] vs 0/10 [1-sided 95% CI: 0%-30.8%], p < 0.0005); this was robust to
      adjustment for age. The original Boston criteria for probable CAA showed a
      sensitivity of 76.9% (95% CI: 46.2%-95%), which increased to 92.3% (95% CI: 64%
      99.8%), without loss of specificity, after including severe centrum semiovale
      PVS. CONCLUSIONS: Severe centrum semiovale PVS on MRI may be a promising new
      neuroimaging marker for the in vivo diagnosis of CAA. However, our findings are
      preliminary and require confirmation and external validation in larger cohorts of
      pathology-proven CAA.

PMID- 24285618
TI  - Cluster RCT of case management on patients' quality of life and caregiver strain
      in ALS.
AB  - OBJECTIVES: To study the effect of case management on quality of life, caregiver
      strain, and perceived quality of care (QOC) in patients with amyotrophic lateral
      sclerosis (ALS) and their caregivers. METHODS: We conducted a multicenter cluster
      randomized controlled trial with the multidisciplinary ALS care team as the unit
      of randomization. During 12 months, patients with ALS and their caregivers
      received case management plus usual care or usual care alone. Outcome measures
      were the 40-item ALS Assessment Questionnaire (ALSAQ-40), Emotional Functioning
      domain (EF); the Caregiver Strain Index (CSI); and the QOC score. These measures
      were assessed at baseline and at 4, 8, and 12 months. RESULTS: Case management
      resulted in no changes in ALSAQ-40 EF, CSI, or QOC from baseline to 12 months.
      ALSAQ-40 EF scores in both groups were similar at baseline and did not change
      over time (p = 0.331). CSI scores in both groups increased significantly (p <
      0.0001). Patients with ALS from both groups rated their perceived QOC at baseline
      with a median score of 8, which did not change significantly during follow-up.
      CONCLUSION: Within the context of multidisciplinary ALS care teams, case
      management appears to confer no benefit for patients with ALS or their
      caregivers. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence
      that case management in addition to multidisciplinary ALS care does not
      significantly improve health-related quality of life of patients with ALS.

PMID- 24285617
TI  - Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a
      randomized trial.
AB  - OBJECTIVES: To test the hypothesis that daily acute intermittent hypoxia (dAIH)
      and dAIH combined with overground walking improve walking speed and endurance in
      persons with chronic incomplete spinal cord injury (iSCI). METHODS: Nineteen
      subjects completed the randomized, double-blind, placebo-controlled, crossover
      study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of
      inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60
      second normoxic intervals on 5 consecutive days; dAIH was given alone or combined
      with 30 minutes of overground walking 1 hour later. Walking speed and endurance
      were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered
      at ClinicalTrials.gov (NCT01272349). RESULTS: dAIH improved walking speed and
      endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean
      difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1-6.5 seconds, p =
      0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9-6.7 seconds, p = 0.010). Six
      Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking
      after 5 days (MD 94.4 m, 95% CI 17.5-171.3 m, p = 0.017) and 1-week follow-up (MD
      97.0 m, 95% CI 20.1-173.9 m, p = 0.014). dAIH + walking increased walking
      distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3-134.1 m, p = 0.046), 5
      days (MD 107.0 m, 95% CI 40.6-173.4 m, p = 0.002), and 1-week follow-up (MD 136.0
      m, 95% CI 65.3-206.6 m, p < 0.001). CONCLUSIONS: dAIH +/- walking improved
      walking speed and distance in persons with chronic iSCI. The impact of dAIH is
      enhanced by combination with walking, demonstrating that combinatorial therapies
      may promote greater functional benefits in persons with iSCI. CLASSIFICATION OF
      EVIDENCE: This study provides Class I evidence that transient hypoxia (through
      measured breathing treatments), along with overground walking training, improves
      walking speed and endurance after iSCI.

PMID- 24285619
TI  - Varicella-zoster virus trigeminal ganglioneuritis without rash.

PMID- 24285620
TI  - Prevalence of ataxia in children: a systematic review.
AB  - OBJECTIVE: To estimate the prevalence of childhood ataxia resulting from both
      genetic and acquired causes. METHODS: A systematic review was conducted following
      the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)
      statement. Five databases were searched for articles reporting a frequency
      measure (e.g., prevalence, incidence) of ataxia in children. Included articles
      were first grouped according to the World Health Organization (WHO) regions and
      subsequently classified according to etiology (genetic, acquired, or mixed). Each
      article was assessed for its risk of bias on the domains of sampling,
      measurement, and analysis. Incidence values were converted to prevalence
      estimates whenever possible. European prevalence estimates for different
      etiologies of ataxia were summed to gauge the overall prevalence of childhood
      ataxia. RESULTS: One hundred fifteen articles were included in the review. More
      than 50% of the data originated from the Europe WHO region. Data from this region
      also showed the least susceptibility to bias. Little data were available for
      Africa and Southeast Asia. The prevalence of acquired ataxias was found to vary
      more greatly across regions than the genetic ataxias. Ataxic cerebral palsy was
      found to be a significant contributor to the overall prevalence of childhood
      ataxia across WHO regions. The prevalence of childhood ataxias in Europe was
      estimated to be ~26/100,000 children and likely reflects a minimum prevalence
      worldwide. CONCLUSIONS: The findings show that ataxia is a common childhood motor
      disorder with a higher prevalence than previously assumed. More research
      concerning the epidemiology, assessment, and treatment of childhood ataxia is
      warranted.

PMID- 24285621
TI  - Dynamic susceptibility contrast MRI with a prebolus contrast agent administration
      design for improved absolute quantification of perfusion.
AB  - PURPOSE: Arterial partial-volume effects (PVEs) often hamper reproducible
      absolute quantification of cerebral blood flow (CBF) and cerebral blood volume
      (CBV) obtained by dynamic susceptibility contrast MRI (DSC-MRI). The aim of this
      study was to examine whether arterial PVEs in DSC-MRI data can be minimized by
      rescaling the arterial input function (AIF) using a sagittal-sinus venous output
      function obtained following a prebolus administration of a low dose of contrast
      agent. METHODS: The study was carried out as a test-retest experiment in 20
      healthy volunteers to examine the repeatability of the CBF and CBV estimates. All
      subjects were scanned twice with 7-20 days between investigations. RESULTS: DSC
      MRI returned an overestimated average whole-brain CBF of 220 +/- 44 mL/100 g/min
      (mean +/- SD) before correction and 44 +/- 15 mL/100 g/min when applying the
      prebolus design, averaged over all scans. Average whole-brain CBV was 20 +/- 2.0
      mL/100 g before correction and 4.0 +/- 1.0 mL/100 g after prebolus correction.
      CONCLUSION: Quantitative estimates of CBF and CBV, obtained with the proposed
      prebolus DSC-MRI technique, approached those typically obtained by other
      perfusion modalities. The CBF and CBV estimates showed good repeatability.

PMID- 24285622
TI  - Preparation and characterization of alkenyl aryl tetrafluoro-lambda(6) -sulfanes.
AB  - Substituted alkenyl aryl tetrafluoro-lambda(6) -sulfanes have been prepared by
      the direct addition of readily accessible chlorotetrafluorosulfanyl arenes to
      primary alkynes. Substitution of an apical fluorine of the pentafluorosulfanyl
      group enables modulation of the reactivity of this little explored functional
      group while at the same time facilitating the direct investigation of aryl
      substituent effects on the aryl tetrafluorosulfanyl-substituted products. 

PMID- 24285624
TI  - Construction of shallow surface states through light Ni doping for high
      efficiency photocatalytic hydrogen production of CdS nanocrystals.
AB  - Ni-doped CdS nanowires were synthesized by a simple one-step method. X-ray
      diffraction, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy
      confirmed that light Ni doping can form shallow surface states due to the
      presence of substitutional Ni ions, and heavy Ni doping can form deep surface
      states due to the presence of interstitial Ni ions. Surface photovoltage
      spectroscopy and transient photovoltage measurements revealed that the shallow
      surface states can prolong the lifetime of the photogenerated charge carriers,
      whereas the deep surface states lead to recombination of the photogenerated
      charge carriers. The relationship between different surface states and the
      photocatalytic performance of CdS nanocrystals are discussed. The enhanced
      density of shallow surface states due to light Ni doping significantly promotes
      photocatalytic H2 production. 

PMID- 24285623
TI  - Eg5 restricts anaphase B spindle elongation in mammalian cells.
AB  - During anaphase, overlapping antiparallel microtubules in the spindle interzone
      elongate and contribute to chromosome segregation. Kinesin-5 family members are
      required for spindle elongation in some cells, but in other cases they restrict
      elongation acting like a brake. To determine how kinesin-5 contributes to spindle
      elongation in mammalian cells, we treated LLC-Pk1 epithelial cells with small
      molecule inhibitors of the mammalian kinesin-5, Eg5, at anaphase onset and
      measured the rate and extent of spindle pole separation using multidimensional
      tracking of centrosomes in cells expressing GFP-gamma-tubulin. Centrosome
      separation was biphasic, with an initial fast phase followed by a slower phase.
      Treatment with the small molecule inhibitor, STLC, which weakens the interaction
      of Eg5 with microtubules, resulted in an increase in the rate of centrosome
      separation. Conversely, treatment with FCPT, which induces a rigor-like
      interaction of Eg5 with microtubules, reduced the rate of spindle elongation. In
      control cells, GFP-Eg5 was localized to spindle microtubules and accumulated in
      the interzone as anaphase progressed. Spindle fluorescence of GFP-Eg5 was
      decreased following treatment with STLC and increased in cells treated with FCPT.
      In anaphase cells, cortical dynein increases and rocking motion of spindle poles
      was detected consistent with the possibility that dynein mediates spindle
      elongation. In summary, our results demonstrate that Eg5 is not required for
      spindle elongation, and in fact, restricts the rate of spindle elongation in
      mammalian cells.

PMID- 24285625
TI  - Nobody's child: the role of trauma and interpersonal violence in women's pathways
      to incarceration and resultant service needs.
AB  - With the rate of women's incarceration significantly outpacing that of men's,
      combined with the fact that the United States has the highest incarceration rate
      in the world, there is an urgent need to delineate incarcerated women's pathways
      to crime and subsequent service needs. This article reports findings of modified
      participant observation and qualitative research conducted from 2008 to 2010 with
      women incarcerated in a large, county jail in North Carolina addressing these
      issues. Thirty life history interviews, nine focus groups, and 60 questionnaires
      reveal the centrality of trauma, particularly in the form of interpersonal
      violence (i.e., sexual, physical, and/or emotional abuse in adulthood and/or
      childhood), in incarcerated women's lives. In the absence of positive resources
      (e.g., counseling, family/friend support), women's attempts to cope with trauma
      increase their risks for incarceration as well as further trauma. In addition to
      providing trauma-based treatment, decreasing women's recidivism requires macro
      level examinations of policies that marginalize women economically and socially. 

PMID- 24285626
TI  - The UK Freedom of Information Act (2000) in healthcare research: a systematic
      review.
AB  - OBJECTIVES: To assess the use and utility of the Freedom of Information Act
      (2000) in healthcare research since 2005 and to determine if any particular
      feature of studies found led to greater data acquisition. DESIGN: PRISMA
      compliant systematic review. PARTICIPANTS: An extensive literature search was
      performed of EMBASE, MEDLINE, CINAHL, psychINFO, BNI, AMED, HMIC and Health
      business elite databases from January 2005 to January 2013 using terms 'Freedom
      of information', 'Freedom of information act' and 'Freedom of information act
      2000'. Papers were considered for publication if they described utilising the UK
      Freedom of information act to gather data for healthcare research. 16 articles
      met these criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was
      the number and characteristics of studies utilising the Freedom of Information
      Act to collect the data for healthcare research. Secondary outcome measures were
      any features that improved data acquisition rates (including to whom the request
      was made, the number of questions asked per request, etc.) RESULTS: 16 articles
      described utilising the Freedom of Information Act for healthcare research, and
      these investigated a broad range of topics. The median number of requests made
      was 86 (range 1-172), the total number of requests was 1732. A total of 15 817
      pieces of data were retrieved by all studies. The amount of data collected was
      defined as the number of questions asked multiplied by the number of full
      responses. A median of five questions were asked per study (range 5-6.5) and the
      overall response rate was 86%. The National Health Service litigation authority
      responded to 100% of requests, while Primary Care Trusts had the lowest response
      rate of 81% for healthcare bodies. A positive correlation between number of
      requests made and data obtained (0.508, p<0.05) and number of requests made and
      increased response rate (0.737, p<0.01), both reached the statistical
      significance. CONCLUSIONS: Researchers should make greater use of the Act to
      access the information they need that is not otherwise disclosed. We discuss the
      issues with the research utilising the Act and how future research of this type
      could be optimised.

PMID- 24285627
TI  - Chronic health conditions and poverty: a cross-sectional study using a
      multidimensional poverty measure.
AB  - OBJECTIVES: To identify the chronic health conditions associated with
      multidimensional poverty. DESIGN: Cross-sectional study of the nationally
      representative Survey of Disability, Ageing and Carers, conducted by the
      Australian Bureau of Statistics. SETTING: Australian population in 2003.
      PARTICIPANTS: 35 704 individuals randomly selected from the Australian population
      by the Australian Bureau of Statistics. OUTCOME MEASURES: Multidimensional
      poverty status, costs of disability, short form 6D health utility score, income,
      education attainment. RESULTS: Among those who were multidimensionally poor, 75%
      had a chronic health condition and the most common health conditions were back
      problems (11% of those in multidimensional poverty had back problems) and
      arthritis (11%). The conditions with the highest proportion of individuals in
      multidimensional poverty were depression/mood affecting disorders (26% in
      multidimensional poverty) and mental and behavioural disorders (22%). Those with
      depression/mood affecting disorders were nearly seven times (OR 6.60, 95% CI 5.09
      to 8.55, p<0.0001) more likely to be multidimensionally poor than those with no
      health condition. Equivalising for the additional costs of disability increased
      the proportion of individuals in multidimensional poverty for all conditions and
      the conditions with the highest proportion of individuals in multidimensional
      poverty changed. CONCLUSIONS: Owing to the influence of certain health conditions
      on poverty status, health interventions have the potential to improve national
      living standards and poverty rates in a similar way that 'traditional' policy
      responses such as changes to welfare payment currently do. Using a
      multidimensional poverty measure reveals the health conditions that should be the
      focus of such efforts.

PMID- 24285628
TI  - A population-based survival analysis describing the association of body mass
      index on time to revision for total hip and knee replacements: results from the
      UK general practice research database.
AB  - OBJECTIVES: Against a backdrop of rising levels of obesity, we describe and
      estimate associations of body mass index (BMI), age and gender with time to
      revision for participants undergoing primary total hip (THR) or knee (TKR)
      replacement in the UK. DESIGN: Population-based cohort study. SETTING: Routinely
      collected primary care data from a representative sample of general practices,
      including linked data on all secondary care events. PARTICIPANTS: Population
      based cohort study of 63 162 patients with THR and 54 276 with TKR in the UK
      General Practice Research Database between 1988 and 2011. PRIMARY AND SECONDARY
      OUTCOMES: Risk of THR and TKR revision associated with BMI, age and gender, after
      adjusting for the competing risk of death. RESULTS: The 5-year cumulative
      incidence rate for THR was 2.2% for men and 1.8% for women (TKR 2.3% for men,
      1.6% for women). The adjusted overall subhazard ratio (SHR) for patients with THR
      undergoing subsequent hip revision surgery, with a competing risk of death, were
      estimated at 1.020 (95% CI 1.009 to 1.032) per additional unit (kg/m(2)) of BMI,
      1.23 (95% CI 1.10 to 1.38) for men compared with women and 0.970 (95% CI 0.967 to
      0.973) per additional year of age. For patients with TKR, the equivalent
      estimates were 1.015 (95% CI 1.002 to 1.028) for BMI; 1.51 (95% CI 1.32 to 1.73)
      for gender and 0.957 (95% CI 0.951 to 0.962) for age. Morbidly obese patients
      with THR had a 65.5% increase (95% CI 15.4% to 137.3%, p=0.006) in the subhazard
      of revision versus the normal BMI group (18.5-25). The effect for TKR was smaller
      (a 43.9% increase) and weaker (95% CI 2.6% to 103.9%, p=0.040). CONCLUSIONS: BMI
      is estimated to have a small but statistically significant association with the
      risk of hip and knee revision, but absolute numbers are small. Further studies
      are needed in order to distinguish between effects for specific revision surgery
      indications.

PMID- 24285629
TI  - Understanding the investigators: a qualitative study investigating the barriers
      and enablers to the implementation of local investigator-initiated clinical
      trials in Ethiopia.
AB  - OBJECTIVES: Clinical trials provide 'gold standard' evidence for policy, but
      insufficient locally relevant trials are conducted in low-income and middle
      income countries. Local investigator-initiated trials could generate highly
      relevant data for national governments, but information is lacking on how to
      facilitate them. We aimed to identify barriers and enablers to investigator
      initiated trials in Ethiopia to inform and direct capacity strengthening
      initiatives. DESIGN: Exploratory, qualitative study comprising of in-depth
      interviews (n=7) and focus group discussions (n=3). SETTING: Fieldwork took place
      in Ethiopia during March 2011. PARTICIPANTS: Local health researchers with
      previous experiences of clinical trials or stakeholders with an interest in
      trials were recruited through snowball sampling (n=20). OUTCOME MEASURES:
      Detailed discussion notes were analysed using thematic coding analysis and key
      themes were identified. RESULTS: All participants perceived investigator
      initiated trials as important for generating local evidence. System and
      organisational barriers included: limited funding allocation, weak regulatory and
      administrative systems, few learning opportunities, limited human and material
      capacity and poor incentives for conducting research. Operational hurdles were
      symptomatic of these barriers. Lack of awareness, confidence and motivation to
      undertake trials were important individual barriers. Training, knowledge sharing
      and experience exchange were key enablers to trial conduct and collaboration was
      unanimously regarded as important for improving capacity. CONCLUSIONS: Barriers
      to trial conduct were found at individual, operational, organisational and system
      levels. These findings indicate that to increase locally led trial conduct in
      Ethiopia, system wide changes are needed to create a more receptive and enabling
      research environment. Crucially, the creation of research networks between
      potential trial groups could provide much needed practical collaborative support
      through sharing of financial and project management burdens, knowledge and
      resources. These findings could have important implications for capacity
      strengthening initiatives but further research is needed before the results can
      be generalised more widely.

PMID- 24285630
TI  - Joint effects of serum ferritin and body mass index on the risk of coronary
      artery disease: a case-control study.
AB  - OBJECTIVES: Serum ferritin and body mass index (BMI) have been reportedly
      associated with coronary artery disease (CAD) risk. The aim of the present study
      was to explore the interaction between serum ferritin and BMI on CAD risk.
      DESIGN: Hospital-based case-control study. SETTING: Patients with CAD and the
      controls were recruited from Qilu Hospital, Shandong University. PARTICIPANTS:
      258 CAD cases and 282 healthy controls. METHODS: Multiplicative interaction was
      assessed through a cross-product interaction term in a multivariate logistic
      regression model. The effect of serum ferritin and BMI were evaluated per 50 ug/L
      and per 2 kg/m(2), respectively. The presence of additive interaction between
      serum ferritin and BMI was evaluated by calculation of the relative excess risk
      due to interaction (RERI), attributable proportion due to interaction (AP) and
      synergy index (S). RESULTS: The ORs and 95% CI of the serum ferritin-BMI product
      term on a multiplicative scale in the univariate and multivariate models were
      0.943 (0.904 to 0.984) and 1.004 (0.951 to 1.059), respectively. There was also
      evidence for interaction on an additive scale; the RERI (95% CI), AP (95% CI) and
      S (95% CI) in the univariate model were 0.314 (0.026 to 1.506), 0.107 (0.017 to
      0.241) and 1.194 (1.053 to 1.406), respectively. After adjusting for the
      potential confounders, the estimates and 95% CIs for the aforementioned three
      measures were 0.004 (-0.016 to 0.311), 0.004 (-0.016 to 0.191) and 1.039 (0.774
      to 1.285), respectively. CONCLUSIONS: Serum ferritin and BMI had an additive
      interaction on the risk of CAD in Chinese population. Further investigations with
      big sample size are necessary for confirming this additive interaction.

PMID- 24285631
TI  - Inequalities in ventilation tube insertion procedures between Aboriginal and non
      Aboriginal children in New South Wales, Australia: a data linkage study.
AB  - OBJECTIVES: Australian Aboriginal children experience earlier, more frequent and
      more severe otitis media, particularly in remote communities, than non-Aboriginal
      children. Insertion of ventilation tubes is the main surgical procedure for
      otitis media. Our aim was to quantify inequalities in ventilation tube insertion
      (VTI) procedures between Australian Aboriginal and non-Aboriginal children, and
      to explore the influence of birth characteristics, socioeconomic background and
      geographical remoteness on this inequality. DESIGN: Retrospective cohort study
      using linked hospital and mortality data from July 2000 to December 2008. SETTING
      AND PARTICIPANTS: A whole-of-population cohort of 653 550 children (16 831
      Aboriginal and 636 719 non-Aboriginal) born in a New South Wales hospital between
      1 July 2000 and 31 December 2007 was included in the analysis. OUTCOME MEASURE:
      First VTI procedure. RESULTS: VTI rates were lower in Aboriginal compared with
      non-Aboriginal children (incidence rate (IR), 4.3/1000 person-years; 95% CI 3.8
      to 4.8 vs IR 5.8/1000 person-years; 95% CI 5.7 to 5.8). Overall, Aboriginal
      children were 28% less likely than non-Aboriginal children to have ventilation
      tubes inserted (age-adjusted and sex-adjusted rate ratios (RRs) 0.72; 95% CI 0.64
      to 0.80). After adjusting additionally for geographical remoteness, Aboriginal
      children were 19% less likely to have ventilation tubes inserted (age-adjusted
      and sex-adjusted RR 0.81; 95% CI 0.73 to 0.91). After adjusting separately for
      private patient/health insurance status and area socioeconomic status, there was
      no significant difference (age-adjusted and sex-adjusted RR 0.96; 95% CI 0.86 to
      1.08 and RR 0.93; 95% CI 0.83 to 1.04, respectively). In the fully adjusted
      model, there were no significant differences in VTI rates between Aboriginal and
      non-Aboriginal children (RR 1.06; 95% CI 0.94 to 1.19). CONCLUSIONS: Despite a
      much higher prevalence of otitis media, Aboriginal children were less likely to
      receive VTI procedures than their non-Aboriginal counterparts; this inequality
      was largely explained by differences in socioeconomic status and geographical
      remoteness.

PMID- 24285632
TI  - Effect of birth weight on the association between necrotising enterocolitis and
      red blood cell transfusions in <=1500 g infants.
AB  - CONTEXT: Reports evaluating a possible association between necrotising
      enterocolitis (NEC) and blood transfusion have been predominantly case-control
      studies. As the possible associations of disease with any variable on which cases
      and controls have been matched cannot be explored, a cohort study would offer a
      solution to this problem. OBJECTIVE: Our objective was to evaluate the
      association between exposure to a packed red blood cell (PRBC) transfusion and
      development of NEC in a cohort where biases of matching are omitted. DESIGN: In a
      retrospective cohort, exposed infants were defined as those who received a
      transfusion and did not develop NEC or developed NEC within 48 h of the
      transfusion. All others were considered unexposed. SETTING: A single regional
      perinatal centre in Memphis, Tennessee, USA. PATIENTS: 3060 <=1500 g birth
      weights (BW) were included. OUTCOME MEASURES: The relative risk of developing NEC
      after exposure to a PRBC transfusion was measured. RESULTS: 3060 infants were
      identified. 174 infants (5.7%) developed NEC; 116 of the 174 infants (67%) were
      exposed. NEC infants had a significantly lower BW (924 vs 1042 g) and required a
      longer stay on a ventilator (7 vs 2 days). Divided into groups, infants with BW
      <=750 , 751-1000 , 1001-1250 g and 1251-1500 g (n=52, 51, 46 and 25,
      respectively) had a relative risk of 0.14, 0.46, 1.83 and 1.78 (p<0.01, 0.02,
      0.07 and 0.17), respectively, to develop NEC after an exposure. Infants with
      longest ventilator days were also significantly less likely to develop NEC after
      an exposure; relative risk=0.11 (p<0.01). CONCLUSIONS: Exposure to transfusions
      was less likely associated with NEC in <=1000 g infants and remained a risk
      factor in 1001-1500 infants. BW has to be factored in any study evaluating the
      association between PRBC transfusions and NEC.

PMID- 24285633
TI  - A descriptive study of access to services in a random sample of Canadian rural
      emergency departments.
AB  - OBJECTIVE: To examine 24/7 access to services and consultants in a sample of
      Canadian rural emergency departments (EDs). DESIGN: Cross-sectional study-mixed
      methods (structured interview, survey and government data bases) with random
      sampling of hospitals. SETTING: Canadian rural EDs (rural small town (RST)
      definition-Statistics Canada). PARTICIPANTS: 28% (95/336) of Canadian rural EDs
      providing 24/7 physician coverage located in hospitals with acute care
      hospitalisation beds. MAIN OUTCOME MEASURES: General characteristics of the rural
      EDs, information about 24/7 access to consultants, equipment and services, and
      the proportion of rural hospitals more than 300 km from levels 1 and 2 trauma
      centres. RESULTS: Of the 336 rural EDs identified, 122 (36%) were randomly
      selected and contacted. Overall, 95 EDs participated in the study (participation
      rate, 78%). Hospitals had, on an average, 23 acute care beds, 7 ED stretchers and
      13 500 annual ED visits. The proportion of rural hospitals with local access to
      the following 24/7 services was paediatrician, 5%; obstetrician, 10%;
      psychiatrist, 11%; internist, 12%; intensive care unit, 17%; CT scanner, 20%;
      surgeon, 26%; ultrasound, 28%; basic X-ray, 97% and laboratory services, 99%.
      Forty-four per cent and 54% of the RST EDs were more than 300 km from a level 1
      and level 2 trauma centre, respectively. CONCLUSIONS: This is the first study
      describing the services available in Canadian rural EDs. Apart from basic
      laboratory and X-ray services, most rural EDs have limited access to consultants,
      advanced imaging and critical care services. A detailed study is needed to
      evaluate the impact of these limited services on patient outcomes, costs and
      interfacility transport demands.

PMID- 24285634
TI  - Time to publication for NIHR HTA programme-funded research: a cohort study.
AB  - OBJECTIVE: To assess the time to publication of primary research and evidence
      syntheses funded by the National Institute for Health Research (NIHR) Health
      Technology Assessment (HTA) Programme published as a monograph in Health
      Technology Assessment and as a journal article in the wider biomedical
      literature. STUDY DESIGN: Retrospective cohort study. SETTING: Primary research
      and evidence synthesis projects funded by the HTA Programme were included in the
      cohort if they were registered in the NIHR research programmes database and was
      planned to submit the draft final report for publication in Health Technology
      Assessment on or before 9 December 2011. MAIN OUTCOME MEASURES: The median time
      to publication and publication at 30 months in Health Technology Assessment and
      in an external journal were determined by searching the NIHR research programmes
      database and HTA Programme website. RESULTS: Of 458 included projects, 184
      (40.2%) were primary research projects and 274 (59.8%) were evidence syntheses. A
      total of 155 primary research projects had a completion date; the median time to
      publication was 23 months (26.5 and 35.5 months to publish a monograph and to
      publish in an external journal, respectively) and 69% were published within 30
      months. The median time to publication of HTA-funded trials (n=126) was 24 months
      and 67.5% were published within 30 months. Among the evidence syntheses with a
      protocol online date (n=223), the median time to publication was 25.5 months (28
      months to publication as a monograph), but only 44.4% of evidence synthesis
      projects were published in an external journal. 65% of evidence synthesis studies
      had been published within 30.0 months. CONCLUSIONS: Research funded by the HTA
      Programme publishes promptly. The importance of Health Technology Assessment was
      highlighted as the median time to publication was 9 months shorter for a
      monograph than an external journal article.

PMID- 24285635
TI  - Comparison of two strategies using pedometers to counteract physical inactivity
      in smokers.
AB  - INTRODUCTION: This randomized crossover trial aimed to compare the effects of 2
      different protocols using pedometers and informative booklets to increase
      physical activity in daily life (PADL) in smokers. METHODS: PADL level was
      assessed at baseline (A1), and subjects were randomly assigned to 2 groups for a
      month: booklet + pedometer (GB + P; n = 13), which started the protocol receiving
      a booklet with encouragement to walk as much as possible in everyday life;
      pedometer + booklet (GP + B; n = 18), which started the protocol wearing a
      pedometer aiming to achieve 10,000 steps/day. PADL was reassessed (A2), and the
      interventions were crossed over for 1 month, followed by PADL reassessment (A3).
      After A3, both groups used pedometers for 3 months aiming to reach 10,000
      steps/day, and final PADL assessment was performed (A4). For the analysis, each
      group was subdivided according to baseline PADL as physically active or inactive,
      according to having reached or not reached 10,000 steps/day at baseline. RESULTS:
      The physically active subgroups of GB + P and GP + B showed no change in
      steps/day. The physically inactive subgroup of GP + B significantly increased
      steps/day at A2 and maintained this increase until A4. The physically inactive
      subgroup of GB + P initially increased to a lesser extent, reaching borderline
      statistical significance at A2 and A3 (p = .06) and statistically significant
      increase only at A4 (p = .02). CONCLUSIONS: Both strategies were effective in
      increasing the number of steps/day in physically inactive smokers after 5 months,
      although the increase was more quickly obtained in smokers who used pedometers as
      the first intervention.

PMID- 24285638
TI  - Reply: To PMID 23554120.

PMID- 24285636
TI  - CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell
      stereocilia in a molecular complex with radixin, taperin, and myosin VI.
AB  - Chloride intracellular channel 5 protein (CLIC5) was originally isolated from
      microvilli in complex with actin binding proteins including ezrin, a member of
      the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5
      concentrates at the base of hair cell stereocilia and is required for normal
      hearing and balance in mice, but its functional significance is poorly
      understood. This study investigated the role of CLIC5 in postnatal development
      and maintenance of hair bundles. Confocal and scanning electron microscopy of
      CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia
      as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase
      receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also
      concentrate at the base of stereocilia, were mislocalized in fused stereocilia of
      jbg mice. TPRQ and RDX were dispersed even prior to stereocilia fusion.
      Biochemical assays showed interaction of CLIC5 with ERM proteins, TPRN, and
      possibly myosin VI (MYO6). In addition, CLIC5 and RDX failed to localize normally
      in fused stereocilia of MYO6 mutant mice. Based on these findings, we propose a
      model in which these proteins work together as a complex to stabilize linkages
      between the plasma membrane and subjacent actin cytoskeleton at the base of
      stereocilia.

PMID- 24285639
TI  - NMR spectroscopy and X-ray characterisation of cationic N-heteroaryl-pyridylamido
      Zr(IV) complexes: a further level of complexity for the elusive active species of
      pyridylamido olefin polymerisation catalysts.
AB  - New [(N(-),N,N(-))ZrR2] dialkyl complexes (N(-),N,N(-)=pyrrolyl-pyridyl-amido or
      indolyl-pyridyl-amido; R=Me or CH2Ph) have been synthesised and tested as pre
      catalysts for ethene and propene polymerisation in combination with different
      activators, such as B(C6F5)3, [Ph3C][B(C6F5)4], [HNMe2Ph][B(C6F5)4] or solid
      AlMe3-depleted methylaluminoxane (DMAO). Polyethylene (M(w)>2 MDa and M(w)/M(n)=
      1.3-1.6) has been produced if pre-catalysts were activated with 1000 equivalents
      of DMAO (based on Al) [activity >1000 kg(PE)(mol([Zr]) h mol atm)(-1)] or by
      using a higher pre-catalyst concentration and a mixture of [HNPhMe2][B(C6F5)4] (1
      equiv) and AliBu2H (60 equiv). In the case of propene polymerisation, activity
      has been observed only if pre-catalysts were treated with an excess of AliBu2H
      prior to addition of DMAO, which led to highly isotactic polypropylene
      ([mmmm]>95%). Neutral pre-catalysts and ion pairs derived from their activation
      have been characterised in solution by using advanced 1D and 2D NMR spectroscopy
      experiments. The detection and rationalisation of intercationic NOEs clearly
      showed the formation of dimeric species in which some pyrrolyl or indolyl pi
      electron density of one unit is engaged in stabilising the metal centre of the
      other unit, which relegates the counterions in the second coordination sphere.
      The solid-state structure of the dimeric indolyl-pyridyl-amidomethylzirconium
      derivative, determined by X-ray diffraction studies, points toward a weak
      Zr...eta(3)-indolyl interaction. It can be hypothesised that the formation of
      dimeric cationic species hampers monomer coordination (especially of less
      reactive alpha-olefins) and that addition of AliBu2H is crucial to split the
      homodimers.

PMID- 24285637
TI  - Crowdsourcing natural products discovery to access uncharted dimensions of fungal
      metabolite diversity.
AB  - A fundamental component for success in drug discovery is the ability to assemble
      and screen compounds that encompass a broad swath of biologically relevant
      chemical-diversity space. Achieving this goal in a natural-products-based setting
      requires access to a wide range of biologically diverse specimens. For this
      reason, we introduced a crowdsourcing program in which citizen scientists furnish
      soil samples from which new microbial isolates are procured. Illustrating the
      strength of this approach, we obtained a unique fungal metabolite, maximiscin,
      from a crowdsourced Alaskan soil sample. Maximiscin, which exhibits a putative
      combination of polyketide synthase (PKS), non-ribosomal peptide synthetase
      (NRPS), and shikimate pathway components, was identified as an inhibitor of UACC
      62 melanoma cells (LC50=0.93 MUM). The metabolite also exhibited efficacy in a
      xenograft mouse model. These results underscore the value of building cooperative
      relationships between research teams and citizen scientists to enrich drug
      discovery efforts.

PMID- 24285640
TI  - Computational mechanics and electro-mechanics in cardiovascular physiology and
      disease.

PMID- 24285641
TI  - Chirality-driven wettability switching and mass transfer.
AB  - Enantioselective wetting: Regulating the surface wettability of materials through
      chiral molecules provides new insight into the design of chiral materials. By
      taking advantage of a reversible conformational transition, smart polymers
      present an ideal platform for translating weak chiral signals into macroscopic
      properties of materials, thus resulting in a distinctive wettability switching
      driven by chirality. 

PMID- 24285643
TI  - Chemical behaviour of a prototype boryl(phosphino)carbene.
AB  - We recently disclosed the synthesis of a novel "push-pull"
      boryl(phosphino)carbene. To determine the influence of this substitution pattern
      on the chemical behaviour, a study into the reactivity of the prototype (1) of
      this new family of B(sp(2))-substituted phosphinocarbenes was undertaken. Carbene
      1 exhibits one of the most common intramolecular rearrangements of singlet
      carbenes, involving a 1,2-mesityl shift, and typical [2+1] cycloaddition
      reactions with electron-poor acrylonitrile. A pronounced alpha,beta-ambiphilic
      character was also shown by the reaction of 1 with benzaldehyde, leading to
      phosphorylalkene 4. Due to its specific electronic properties, carbene 1 also
      exhibits unprecedented reactivity with chloroacrylonitrile, enabling the
      formation of bicyclo[1.1.0]phosphetanium salt 6 and borylcyclopropene 9, which
      have been fully characterised by NMR spectroscopy and X-ray crystallography.

PMID- 24285642
TI  - The caudate: a key node in the neuronal network imbalance of insomnia?
AB  - Insomnia is prevalent, severe and partially heritable. Unfortunately, its
      neuronal correlates remain enigmatic, hampering the development of mechanistic
      models and rational treatments. Consistently reported impairments concern
      fragmented sleep, hyper-arousal and executive dysfunction. Because fronto
      striatal networks could well play a role in sleep, arousal regulation and
      executive functioning, the present series of studies used an executive task to
      evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia
      showed reduced recruitment of the head of the left caudate nucleus during
      executive functioning, which was not secondary to altered performance or baseline
      perfusion. Individual differences in caudate recruitment were associated with
      hyper-arousal severity. Seed-based functional connectivity analysis suggested
      that attenuated input from a projecting orbitofrontal area with reduced grey
      matter density contributes to altered caudate recruitment in patients with
      insomnia. Attenuated caudate recruitment persisted after successful treatment of
      insomnia, warranting evaluation as a potential vulnerability trait. A similar
      selective reduction in caudate recruitment could be elicited in participants
      without sleep complaints by slow-wave sleep fragmentation, providing a model to
      facilitate investigation of the causes and consequences of insomnia. 

PMID- 24285644
TI  - Highly stereoselective recognition and deracemization of amino acids by
      supramolecular self-assembly.
AB  - The highly stereoselective supramolecular self-assembly of alpha-amino acids with
      a chiral aldehyde derived from binol and a chiral guanidine derived from
      diphenylethylenediamine (dpen) to form the imino acid salt is reported. This
      system can be used to cleanly convert D-amino acids into L-amino acids or vice
      versa at ambient temperature. It can also be used to synthesize alpha-deuterated
      D- or L-amino acids. A crystal structure of the ternary complex together with DFT
      computation provided detailed insight into the origin of the stereoselective
      recognition of amino acids. 

PMID- 24285645
TI  - Draft Genome Sequence of Serratia fonticola UTAD54, a Carbapenem-Resistant Strain
      Isolated from Drinking Water.
AB  - Serratia fonticola UTAD54 is an environmental isolate that is resistant to
      carbapenems due to the presence of a class A carbapenemase and a metallo-beta
      lactamase that are unique to this strain. Its draft genome sequence was obtained
      to clarify the molecular basis of its carbapenem resistance and identify the
      genomic context of its carbapenem resistance determinants. 

PMID- 24285646
TI  - Genome Sequence of Rickettsia gravesii, Isolated from Western Australian Ticks.
AB  - Rickettsia gravesii is a new Rickettsia species closely related to the human
      pathogen Rickettsia massiliae. Here, we describe the genome sequence of R.
      gravesii strain BWI-1, isolated from Amblyomma triguttatum triguttatum ticks
      collected from humans on Barrow Island, Western Australia. 

PMID- 24285647
TI  - Complete Genome Sequence of Carnobacterium gilichinskyi Strain WN1359T (DSM
      27470T).
AB  - We report the complete genome sequence of Carnobacterium gilichinskyi strain
      WN1359, previously isolated from Siberian permafrost and capable of growth under
      cold (0 degrees C), anoxic, CO2-dominated, low-pressure (0.7-kPa) conditions in a
      simulation of the Mars atmosphere. 

PMID- 24285648
TI  - Genome Sequence of Mycoplasma parvum (Formerly Eperythrozoon parvum), a
      Diminutive Hemoplasma of the Pig.
AB  - We report the complete genome sequence of Mycoplasma parvum strain Indiana. Its
      circular chromosome is 564,395 bp, which is smaller than that of Mycoplasma
      genitalium, which was previously considered the smallest member of the
      Mollicutes. Comparative analyses of the genomes of M. parvum and Mycoplasma suis
      will provide novel insights into the molecular basis of their virulence. 

PMID- 24285649
TI  - Draft Genome Sequence of Pseudomonas sp. Strain CMAA 1215, a Plant Growth
      Promoting Bacterium Isolated from a Brazilian Mangrove.
AB  - The aim of this study was to sequence the genome of the plant growth-promoting
      Pseudomonas sp. strain CMAA 1215, an osmotolerant bacterium isolated from
      mangrove soil. 

PMID- 24285650
TI  - Complete Genome Sequence of the Solvent Producer Clostridium saccharobutylicum
      NCP262 (DSM 13864).
AB  - Clostridium saccharobutylicum was employed for the production of acetone and
      butanol in South Africa until the 1970s. The genome comprises a single replicon
      (5,107,814 bp) harboring all the genes necessary for solvent production and the
      degradation of various organic compounds, such as fructose, cellobiose, sucrose,
      and mannose. 

PMID- 24285651
TI  - Draft Genome Sequence of Lactobacillus jensenii Strain MD IIE-70(2).
AB  - A draft genome sequence of Lactobacillus jensenii strain MD IIE-70(2) was
      determined using Ion PGM technology. The reads were mapped to a reference strain
      and assembled using a combination of tools. The genetic features revealed in this
      study will assist in understanding the probiotic properties of Lactobacillus
      bacteria. 

PMID- 24285652
TI  - Draft Genome Sequence of Lactobacillus fermentum Strain 3872.
AB  - This report describes a draft genome sequence of Lactobacillus fermentum strain
      3872. The data revealed remarkable similarity to and dissimilarity with the
      published genome sequences of other strains of the species. The absence of and
      variation in structures of some adhesins and the presence of an additional
      adhesin may reflect adaptation of the bacterium to different host systems and may
      contribute to specific properties of this strain as a new probiotic. 

PMID- 24285653
TI  - Whole-Genome Sequences of Two Beak and Feather Disease Viruses in the Endangered
      Swift Parrot (Lathamus discolor).
AB  - Two complete genomes of beak and feather disease virus (BFDV) were characterized
      from Lathamus discolor, the Australian swift parrot. This is the first report of
      BFDV complete genome sequences in this host. The completed BFDV genomes consist
      of 1,984 nucleotides encoding two open reading frames with 99.7% pairwise
      nucleotide identity. 

PMID- 24285654
TI  - Characterization of the Complete Genome Sequence of a Beak and Feather Disease
      Virus from a Moluccan Red Lory (Eos bornea).
AB  - The complete genome sequence of a beak and feather disease virus (BFDV) encoding
      two major open reading frames (ORFs) was characterized in a wild Moluccan red
      lory (Eos bornea). This is the first report of a BFDV genome from Indonesia and
      the first reported BFDV infection for this host species. 

PMID- 24285655
TI  - Complete genome sequences of 63 mycobacteriophages.
AB  - Mycobacteriophages are viruses that infect mycobacterial hosts. The current
      collection of sequenced mycobacteriophages-all isolated on a single host strain,
      Mycobacterium smegmatis mc(2)155, reveals substantial genetic diversity. The
      complete genome sequences of 63 newly isolated mycobacteriophages expand the
      resolution of our understanding of phage diversity. 

PMID- 24285656
TI  - Draft Genome Sequences of Multidrug-Resistant Acinetobacter sp. Strains from
      Colombian Hospitals.
AB  - The draft genome sequences of the strains Acinetobacter baumannii 107m,
      Acinetobacter nosocomialis 28F, and Acinetobacter pittii 42F, isolated from
      Colombian hospitals, are reported here. These isolates are causative of
      nosocomial infections and are classified as multidrug resistant, as they showed
      resistance to four different antibiotic groups. 

PMID- 24285657
TI  - Complete Genome Sequence of pAP13, a Large Linear Plasmid of a Brevibacterium
      Strain Isolated from a Saline Lake at 4,200 Meters above Sea Level in Argentina.
AB  - pAP13 is an 89-kb linear plasmid hosted by Brevibacterium sp. strain Ap13, an
      actinobacterium isolated from the feces of a flamingo from an extremely high
      altitude lake in Argentina. Because of the ecological importance of the genus
      Brevibacterium, the absolute lack of information concerning Brevibacterium linear
      plasmids, and the possible ecological significance of this unusual plasmid, pAP13
      was completely sequenced, including the inversely oriented termini. 

PMID- 24285658
TI  - Complete Genome Sequence of the Mesoplasma florum W37 Strain.
AB  - Mesoplasma florum is a small-genome fast-growing mollicute that is an attractive
      model for systems and synthetic genomics studies. We report the complete 825,824
      bp genome sequence of a second representative of this species, M. florum strain
      W37, which contains 733 predicted open reading frames and 35 stable RNAs. 

PMID- 24285659
TI  - First complete sequence of a giant linear plasmid from a micrococcus strain
      isolated from an extremely high-altitude lake.
AB  - Micrococcus sp. strain V7, an actinobacterial strain adapted to the extreme
      conditions of the Laguna Vilama, an extremely high-altitude (4,600 m above sea
      level) lake in the Argentinian Puna, was found to carry the giant linear plasmid
      pLMV7. We determined its sequence (92,815 bp) as a prerequisite to the
      investigation of its role in survival in such a harsh environment. 

PMID- 24285660
TI  - Complete Genome Sequence of a Novel Iflavirus from the Transcriptome of
      Halyomorpha halys, the Brown Marmorated Stink Bug.
AB  - We report the genome sequence of a novel iflavirus recovered from the
      transcriptome of a colony of the brown marmorated stink bug, Halyomorpha halys.
      The genome is 9,263 nucleotides (nt) and contains an open reading frame (ORF)
      encoding a 3,017-amino-acid polyprotein. 

PMID- 24285661
TI  - Draft Genome Sequence of Mycobacterium bovis 04-303, a Highly Virulent Strain
      from Argentina.
AB  - Mycobacterium bovis strain 04-303 was isolated from a wild boar living in a free
      ranging field in Argentina. This work reports the draft genome sequence of this
      highly virulent strain and the genomic comparison of its major virulence-related
      genes with those of M. bovis strain AF2122/97 and Mycobacterium tuberculosis
      strain H37Rv. 

PMID- 24285662
TI  - Changuinola Virus Serogroup, New Genomes within the Genus Orbivirus (Family
      Reoviridae) Isolated in the Brazilian Amazon Region.
AB  - We report here the first complete genome sequence of a Changuinola virus (CGLV)
      serotype Irituia virus (BE AN 28873) isolated from a wild rodent (Oryzomys
      goeldi) in the municipality of Ipixuna, State of Para, northern Brazil. All
      genome segments showed similarity with those belonging to members of the genus
      Orbivirus, family Reoviridae. 

PMID- 24285663
TI  - Whole-genome analysis of influenza B viruses of multiple genotypes cocirculating
      in India.
AB  - Systematic influenza virus surveillance has been carried out in India since 2004
      and has revealed the cocirculation of type B lineages. The genetic diversity of
      influenza B viruses was observed when full-genome analysis was performed. In
      2010, the cocirculation of multiple genotypes was observed. 

PMID- 24285664
TI  - Draft Genome Sequence of Marine Cyanobacterium Synechococcus sp. Strain
      NKBG15041c.
AB  - Synechococcus sp. strain NKBG15041c was isolated as a fast-growing marine
      cyanobacterium. Genetic transformation techniques using this strain have been
      well established for metabolic engineering. Here we report the draft genome
      sequence for this strain, consisting of 44 contigs containing a total of
      3,180,043 bp and 3,224 putative protein-coding genes. 

PMID- 24285665
TI  - Complete Genome Sequence of Lactococcus lactis subsp. lactis KLDS4.0325.
AB  - We report the complete genome sequence of Lactococcus lactis subsp. lactis
      KLDS4.0325, a probiotic bacterium isolated from homemade koumiss in Xinjiang,
      China. We have determined the complete genome sequence of strain KLDS4.0325,
      which consists of a chromosome and three plasmids and reveals genes that are
      likely to be involved in dairy fermentation and that have probiotic qualities. 

PMID- 24285666
TI  - Genome Sequence of the Extreme Obligate Alkaliphile Bacillus marmarensis Strain
      DSM 21297.
AB  - Bacillus marmarensis strain DSM 21297 is an extreme obligate alkaliphile able to
      grow in medium up to pH 12.5. A whole-shotgun strategy and de novo assembly led
      to the generation of a 4-Mbp genome of this strain. The genome features
      alkaliphilic adaptations and pathways for n-butanol and poly(3-hydroxybutyrate)
      synthesis. 

PMID- 24285667
TI  - Genome sequences of five b1 subcluster mycobacteriophages.
AB  - Mycobacteriophages infect members of the Mycobacterium genus in the phylum
      Actinobacteria and exhibit remarkable diversity. Genome analysis groups the
      thousands of known mycobacteriophages into clusters, of which the B1 subcluster
      is currently the third most populous. We report the complete genome sequences of
      five additional members of the B1 subcluster. 

PMID- 24285668
TI  - Male fertility and varicocoele: role of immune factors.
AB  - The role of antisperm antibodies (ASA) in the aetiopathogenesis of varicocoele
      related male infertility remains unclear. The objective of this study was to
      determine whether varicocoele is associated with antisperm immune response and
      whether this factor provides additional affect on male fertility. We performed a
      multicentral, prospective study that included the clinical examination of 1639
      male subjects from infertile couples and 90 fertile men, the evaluation of the
      absolute and relative risks of immune infertility associated with varicocoele and
      the impact of the autoimmune response on the semen quality. The methods used were
      as follows: standard examination of seminal fluid according to WHO criteria; ASA
      detection in seminal fluid using mixed antiglobulin reaction (MAR) and direct
      flow cytometry; measurement of spontaneous and ionophore-induced acrosome
      reactions; oxidative stress evaluation with luminal-dependent chemiluminescence
      method and evaluation of DNA fragmentation by sperm chromatin dispersion. The
      prevalence of varicocoele-related immune infertility is about 15% and does not
      depend on the grade of vein dilatation both in primary and secondary fertility
      disorders. Varicocoele is not an immediate cause of autoimmune reactions against
      spermatozoa, but is a cofactor increasing ASA risk; the OR of immune infertility
      after a testicular trauma in varicocoele patients increases twofold. In
      varicocoele patients, the autoimmune antisperm reaction is accompanied by a more
      significant decrease in the semen quality (concentration and number of
      progressively motile and morphologically normal spermatozoa in the ejaculate),
      acrosome reaction disorders (presence of pre-term spontaneous and lack of induced
      reactions) and an increase in the proportion of spermatozoa with DNA
      fragmentation. These disorders correlate with the level of sperm oxidative
      stress; reactive oxygen species (ROS) production in ASA-positive varicocoele
      patients is 2.8 and 3.5 times higher than in ASA-negative varicocoele patients
      and fertile men respectively. We did not find correlation between the grade of
      spermatic cord vein dilatation and ROS production. 

PMID- 24285669
TI  - Biomarkers of exocrine pancreatic injury in 2 rat acute pancreatitis models.
AB  - Consistent, sensitive biomarkers of exocrine pancreatic injury (EPIJ) in animal
      models and humans have historically represented a poorly met need for
      investigators and clinicians. EXPERIMENTAL DESIGN: Sprague-Dawley
      CD/International Genetic Standard system (IGS) rats were administered cerulein or
      cyanohydroxybutene (CHB) to induce EPIJ. Serum samples were taken at time points
      between 1- and 168-hr postinjection (PI), and rats were sacrificed between 24-
      and 168-hr PI. METHOD: We investigated a series of serum-based biomarkers
      including amylase, lipase, pancreas-enriched microRNAs (miRs) and inflammation
      biomarkers compared with concurrent hematology and pancreatic histology. RESULTS
      AND CONCLUSION: Microscopic EPIJ was not associated with consistent changes in
      hematology or inflammation biomarkers. Increased severity scores for EPIJ
      correlated with increased amylase and lipase values, although severity of EPIJ
      did not always correlate with the magnitude of enzyme increases. Microscopic EPIJ
      was most severe at 24 to 48 hr; increases in miR-216a (32-fold) and miR-375 (23
      fold) were present at 24 hr and, along with enzymes, were normalized by 48 hr in
      the cerulein study. MiRs-216a and 375 were increased by ~800- and 500-fold,
      respectively, at 24 hr while miR-375 remained elevated until 72 hr in the CHB
      study. Impact statement: Pancreas-enriched miRs hold promise as novel serum-based
      biomarkers for EPIJ.

PMID- 24285671
TI  - Regenerative medicine of the gastrointestinal tract.
AB  - Regenerative biology/tissue engineering offers potential solutions for the repair
      and augmentation of diseased tissues and organs. Tissue engineering technology
      platforms currently under development for organ regeneration may function in part
      by recapitulating key mechanistic and signaling pathways associated with
      embryonic organogenesis. Temporal observations of observed morphological outcomes
      from the regeneration of tubular organs provide insights into the mechanisms of
      action associated with the activation of regenerative pathways in preclinical
      animal models and humans. These include induction of a neo-blastema, regeneration
      of laminarily organized mural elements (i.e., lamina propria, sub-mucosa, and
      muscularis), and formation of context appropriate transitional junctions at the
      point of anastomosis with other tissue elements. These results provide the
      foundation for a regenerative technology applicable to hollow organs of the
      gastrointestinal (GI) tract including esophagus and small intestine. Factors
      affecting the efficacy of observed regenerative outcomes within the GI tract
      include the roles of vascularization, innervations, and mesenchymal signaling.
      These will be discussed in the context of an overall mechanism of adult
      regeneration potentially applicable by the tissue engineering and regenerative
      medicine industry for continued development of hollow neo-organ products. 

PMID- 24285670
TI  - Leukocyte-epithelial interactions and mucosal homeostasis.
AB  - Many common inflammatory disorders are characterized by the infiltration of
      neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of
      critical barrier function that protects from microbes and noxious agents. In such
      conditions, disease symptoms are complex but directly related to leukocyte
      effects on the barrier and epithelial cell function. It is now highly regarded
      that cellular factors such as cytokines and receptor-ligand interactions
      mediating adhesion of leukocytes to epithelial cells have potent effects on
      epithelial homeostasis, defined by coordinated proliferation, migration,
      differentiation, and regulated cell shedding. Certain cytokines, for example, not
      only alter leukocyte interactions with epithelia through changes in expression of
      adhesion molecules but also affect barrier function through alterations in the
      composition and dynamics of intercellular junctions. In particular, inflammation
      induced loss of many tight junction molecules, in part, can account for
      dysregulated cellular proliferation, migration, survival, and barrier function.
      This review will highlight how neutrophils interact with epithelial cells with
      particular focus on adhesion molecules involved and signaling events that play
      roles in regulating mucosal homeostasis and pathobiology. A better understanding
      of these molecular events may provide new ideas for therapeutics directed at
      attenuating consequences of pathologic inflammation of mucosal surfaces. 

PMID- 24285672
TI  - Gut microbiota, low-grade inflammation, and metabolic syndrome.
AB  - The intestinal tract is inhabited by a large diverse community of bacteria
      collectively referred to as the gut microbiota. Alterations in gut microbiota
      composition are associated with a variety of disease states including obesity,
      diabetes, and inflammatory bowel disease (IBD). Transplant of microbiota from
      diseased persons (or mice) to germfree mice transfers some aspects of disease
      phenotype, indicating that altered microbiota plays a role in disease
      establishment and manifestation. There are myriad potential mechanisms by which
      alterations in gut microbiota might promote disease, including increasing energy
      harvest, production of toxic metabolites, and molecular mimicry of host proteins.
      However, our research indicates that an overarching mechanism by which an
      aberrant microbiota negatively impacts health is by driving chronic inflammation.
      More specifically, we hypothesize that the histopathologically evident gut
      inflammation that defines IBD is a severe but relatively rare outcome of an
      altered host-microbiota relationship, while a much more common consequence of
      such disturbances is "low-grade" inflammation characterized by elevated
      proinflammatory gene expression that associates with, and may promote, metabolic
      syndrome. In this context, a variety of chronic inflammatory diseases may stem
      from inability of the mucosal immune system to properly manage a stable healthy
      relationship with the gut microbiota. While one's ability to manage their gut
      microbiota is dictated in part by genetics, it can be markedly influenced by the
      composition of the microbiota one inherits from their early environment.
      Moreover, the host-microbiota relationship can be perturbed by instigator
      bacteria or dietary components, which may prove to play a role in promoting
      chronic inflammatory disease states. 

PMID- 24285673
TI  - Osteoporosis-bone remodeling and animal models.
AB  - Osteoporosis is a very common skeletal disorder characterized by reduced bone
      mass and altered trabecular microarchitecture that leads to bone fragility and
      fractures. Such disease is due to alterations of the remodeling process that
      occurs in the basic multicellular units that are transitory cellular complexes
      including an osteoclastic phase (osteoclast activation and resorption of
      microscopic portions of bone), a reversion phase (osteoclast replacement by so
      called postosteoclastic cells), and an osteoblastic phase (osteoblastic
      reconstruction of the resorbed bone matrix till the initial volume is regained).
      Bone remodeling is regulated by a number of systemic and local factors; among the
      former, besides physical activity and mechanical stresses, a primary role is
      played by hormones such as parathyroid hormone, vitamin D metabolites, estrogens,
      calcitonin, and glucocorticoids; among the latter, several growth factors
      (macrophage colony-stimulating factor, transforming growth factor beta, platelet
      derived growth factor, fibroblast growth factor 1, bone morphogenetic protein,
      and insulin-like growth factor 1), as well as the osteoprotegerin-receptor
      activator of nuclear factor-kappa B ligand system and the sclerostin, play a
      primary function. The remodeling phases can be evaluated by static and dynamic
      histomorphometry. Their abnormalities may lead to several osteopathies, the most
      common of which is osteoporosis (above all senile and postmenopausal), a rather
      elusive disease chiefly due to its slow development. The use of animal models in
      its study is emphasized.

PMID- 24285675
TI  - Total synthesis of (+/-)-frondosin B and (+/-)-5-epi-liphagal by using a concise
      (4+3) cycloaddition approach.
AB  - A recently developed (4+3) cycloaddition between dienes and furfuryl alcohols, as
      precursors of oxyallyl-type cations, has been used as a key step in the racemic
      syntheses of two natural products: frondosin B and liphagal. This work
      demonstrates the synthetic potential of this cycloaddition reaction, and offers a
      short synthetic route to an interesting family of natural products. A full
      account of these synthetic studies is presented, further illustrating the
      mechanism, scope, and limitations of this straightforward synthetic method for
      seven-membered rings.

PMID- 24285674
TI  - Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): an initial
      survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC).
AB  - BACKGROUND: Randomized clinical trials in pediatric aplastic anemia (AA) are rare
      and data to guide standards of care are scarce. PROCEDURE: Eighteen pediatric
      institutions formed the North American Pediatric Aplastic Anemia Consortium to
      foster collaborative studies in AA. The initial goal of NAPAAC was to survey the
      diagnostic studies and therapies utilized in AA. RESULTS: Our survey indicates
      considerable variability among institutions in the diagnosis and treatment of AA.
      There were areas of general consensus, including the need for a bone marrow
      evaluation, cytogenetic and specific fluorescent in situ hybridization assays to
      establish diagnosis and exclude genetic etiologies with many institutions
      requiring results prior to initiation of immunosuppressive therapy (IST); uniform
      referral for hematopoietic stem cell transplantation as first line therapy if an
      HLA-identical sibling is identified; the use of first-line IST containing horse
      anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling
      donor is not identified; supportive care measures; and slow taper of CSA after
      response. Areas of controversy included the need for telomere length results
      prior to IST, the time after IST initiation defining a treatment failure; use of
      hematopoietic growth factors; the preferred rescue therapy after failure of IST;
      the use of specific hemoglobin and platelet levels as triggers for transfusion
      support; the use of prophylactic antibiotics; and follow-up monitoring after
      completion of treatment. CONCLUSIONS: These initial survey results reflect
      heterogeneity in diagnosis and care amongst pediatric centers and emphasize the
      need to develop evidence-based diagnosis and treatment approaches in this rare
      disease.

PMID- 24285676
TI  - Pancreatic alpha-cell hyperplasia: facts and myths.
AB  - CONTEXT: Pancreatic alpha-cell hyperplasia (ACH) was once an esoteric
      pathological entity, but it has become an important differential diagnosis of
      hyperglucagonemia after inactivating glucagon receptor (GCGR) genomic mutations
      were found in patients with ACH. Recently, the controversy over the pancreatic
      effects of incretins has stimulated much discussion of ACH that often includes
      inaccurate statements not supported by the literature. DATA ACQUISITION:
      Literature related to ACH was reviewed. EVIDENCE SYNTHESIS: ACH is defined as a
      diffuse and specific increase in the number of alpha-cells. A dozen cases have
      been reported and fall into three clinical types: reactive, functional, and
      nonfunctional. Characterized by remarkable hyperglucagonemia without glucagonoma
      syndrome, reactive ACH is caused by inactivating GCGR mutations, and its main
      clinical significance is pancreatic neuroendocrine tumors diagnosed at middle
      age. The Gcgr(-/-) mice, a model of reactive ACH, exhibit a multistage
      tumorigenesis in their pancreata. Pharmacological agents that inhibit glucagon
      signaling also cause reactive ACH in animals and possibly in humans as well. The
      pancreata of incretin-treated humans and those of reactive ACH murine models
      share similarities. Functional ACH features hyperglucagonemia with glucagonoma
      syndrome. Nonfunctional ACH is associated with normal glucagon levels. The causes
      of functional and nonfunctional ACH are unknown as yet. CONCLUSIONS: ACH is a
      histological diagnosis and clinically heterogeneous. Caused by GCGR mutations,
      reactive ACH is a preneoplastic lesion giving rise to slow-developing pancreatic
      neuroendocrine tumors. The effects of treatments targeting glucagon signaling in
      this regard remain controversial. The strong negative feedback control of
      glucagon signaling conserved in all mammals studied, including humans, makes long
      term pancreatic tumor surveillance advisable for the glucagon signaling-targeting
      therapies.

PMID- 24285677
TI  - Age-dependent decline in acyl-ghrelin concentrations and reduced association of
      acyl-ghrelin and growth hormone in healthy older adults.
AB  - BACKGROUND: Acyl-ghrelin is thought to have both orexigenic effects and to
      stimulate GH release. A possible cause of the anorexia of aging is an age
      dependent decrease in circulating acyl-ghrelin levels. OBJECTIVES: The purpose of
      the study was to compare acyl-ghrelin and GH concentrations between healthy old
      and young adults and to examine the relationship of acyl-ghrelin and GH secretion
      in both age groups. METHODS: Six healthy older adults (age 62-74 y, body mass
      index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass
      index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone
      measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house,
      two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in
      a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution
      analysis. The acyl-ghrelin/GH association was estimated from correlations between
      amplitudes of individual GH secretory events and the average acyl-ghrelin
      concentration in the 60-minute interval preceding each GH burst. RESULTS: Twenty
      four-hour mean (+/-SEM) GH (0.48 +/- 0.14 vs 2.2 +/- 0.3 MUg/L, P < .005) and
      acyl-ghrelin (14.7 +/- 2.3 vs 27.8 +/- 3.9 pg/mL, P < .05) levels were
      significantly lower in older adults compared with young adults. Twenty-four-hour
      cortisol concentrations were higher in the old than the young adults (15.1 +/-
      1.0 vs 10.6 +/- 0.9 MUg/dL, respectively, P < .01). The ghrelin/GH association
      was more than 3-fold lower in the older group compared with the young adults
      (0.16 +/- 0.12 vs 0.69 +/- 0.04, P < .001). CONCLUSIONS: These results provide
      further evidence of an age-dependent decline in circulating acyl-ghrelin levels,
      which might play a role both in the decline of GH and in the anorexia of aging.
      Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are
      less tightly linked to GH regulation.

PMID- 24285678
TI  - Predictors of decreasing glomerular filtration rate and prevalence of chronic
      kidney disease after treatment of primary aldosteronism: renal outcome of 213
      cases.
AB  - CONTEXT: In primary aldosteronism (PA), glomerular hyperfiltration due to
      excessive aldosterone is considered to underestimate actual renal damage.
      OBJECTIVE: Our objectives were to determine the prevalence of chronic kidney
      disease (CKD) in PA and identify the predictors of decreasing estimated
      glomerular filtration rate (eGFR) after treatment. DESIGN AND SETTING: This was a
      12-month prospective study of patients with PA treated at Tohoku University
      Hospital. PATIENTS AND INTERVENTIONS: All patients were treated according to the
      results of adrenal venous sampling; 102 patients with aldosterone-producing
      adenoma underwent adrenalectomy, and 111 with bilateral hyperaldosteronism were
      treated with mineralocorticoid receptor antagonists. MAIN OUTCOME MEASURES:
      Electrolytes, blood pressure, and indicators of renal function were determined at
      1 and 12 months after intervention. RESULTS: Blood pressure, urinary albumin
      excretion (UAE), and eGFR, which significantly decreased at 1 month after
      treatment of PA, did not further decrease at 12 months. Prevalence of CKD, which
      was 15.7% in aldosterone-producing adenoma and 8.1% in bilateral
      hyperaldosteronism at the first visit, increased to 37.1% and 28.3%,
      respectively, at the end of study (P < .0001). Multivariate regression analysis
      revealed that higher UAE and lower serum potassium levels were found to be
      independent predictors of decreasing eGFR after intervention. CONCLUSIONS: This
      large cohort study shows that the prevalence of CKD in PA was increased after
      treatment and that higher UAE and lower serum potassium levels at the first visit
      were predictors of decreasing eGFR after treatment of PA. To prevent a large
      decrease of eGFR after intervention, PA patients should be diagnosed before
      evolution to severe albuminuria and hypokalemia.

PMID- 24285679
TI  - Unstimulated highly sensitive thyroglobulin in follow-up of differentiated
      thyroid cancer patients: a meta-analysis.
AB  - CONTEXT: Serum thyroglobulin (Tg) is an indicator of differentiated thyroid
      cancer (DTC) relapse. OBJECTIVE: Our objective was to conduct a meta-analysis of
      published data about the diagnostic performance of highly sensitive serum Tg
      (hsTg) during levothyroxine therapy in DTC follow-up. DATA SOURCES: We performed
      a comprehensive literature search of PubMed/MEDLINE and Scopus for studies
      published until July 2013. STUDY SELECTION: Studies investigating the diagnostic
      performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria
      were 1) articles not within the field of interest; 2) reviews, letters, or
      conference proceedings; 3) articles evaluating serum Tg measurement with a
      functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5)
      insufficient data to reassess diagnostic performance of basal serum hsTg. DATA
      EXTRACTION: Information was collected concerning basic study data, patient
      characteristics, and technical aspects. For each study, the number of true
      positive, false-positive, true-negative, and false-negative findings for basal
      hsTg, considering stimulated Tg measurement as a reference standard, were
      recorded. DATA SYNTHESIS: Pooled data demonstrated that the negative predictive
      value of hsTg was 97% and 99% considering a stimulated Tg measurement >1 ng/mL
      and >2 ng/mL as cutoffs for positivity, respectively. Despite the high pooled
      sensitivity of basal hsTg, the pooled specificity, accuracy, and positive
      predictive value were insufficient to completely substitute for a stimulated Tg
      measurement. CONCLUSIONS: Basal hsTg measurement has a very high negative
      predictive value but an insufficient positive predictive value for monitoring DTC
      patients. Therefore, a Tg stimulation test can be avoided in patients with an
      undetectable basal hsTg, whereas a stimulated Tg measurement should be considered
      when hsTg levels are detectable.

PMID- 24285680
TI  - Vitamin D protects human endothelial cells from oxidative stress through the
      autophagic and survival pathways.
AB  - CONTEXT: Recently, vitamin D (VitD) has been recognized as increasingly
      importance in many cellular functions of several tissues and organs other than
      bone. In particular, VitD showed important beneficial effects in the
      cardiovascular system. Although the relationship among VitD, endothelium, and
      cardiovascular disease is well established, little is known about the antioxidant
      effect of VitD. OBJECTIVE: Our objective was to study the intracellular pathways
      activated by VitD in cultured human umbilical vein endothelial cells undergoing
      oxidative stress. DESIGN: Nitric oxide production, cell viability, reactive
      oxygen species, the mitochondrial permeability transition pore, membrane
      potential, and caspase-3 activity were measured during oxidative stress induced
      by administration of 200 MUM hydrogen peroxide for 20 minutes. Experiments were
      repeated in the presence of specific vitamin D receptor ligand ZK191784. RESULTS:
      Pretreatment with VitD alone or in combination with ZK191784 is able to reduce
      the apoptosis-related gene expression, involving both intrinsic and extrinsic
      pathways. At the same time, it has been shown the activation of pro-autophagic
      beclin 1 and the phosphorylation of ERK1/2 and Akt, indicating a modulation
      between apoptosis and autophagy. Moreover, VitD alone or in combination with
      ZK191784 is able to prevent the loss of mitochondrial potential and the
      consequent cytochrome C release and caspase activation. CONCLUSIONS: The present
      study shows that VitD may prevent endothelial cell death through modulation of
      the interplay between apoptosis and autophagy. This effect is obtained by
      inhibiting superoxide anion generation, maintaining mitochondria function and
      cell viability, activating survival kinases, and inducing NO production.

PMID- 24285681
TI  - Evidence that increased ovarian aromatase activity and expression account for
      higher estradiol levels in African American compared with Caucasian women.
AB  - CONTEXT: Serum estradiol levels are significantly higher across the menstrual
      cycle in African American (AAW) compared with Caucasian women (CW) in the
      presence of similar FSH levels, yet the mechanism underlying this disparity is
      unknown. OBJECTIVE: The objective of the study was to determine whether higher
      estradiol levels in AAW are due to increased granulosa cell aromatase mRNA
      expression and activity. DESIGN: The design of the study included daily blood
      sampling and dominant follicle aspirations at an academic medical center during a
      natural menstrual cycle. SUBJECTS: Healthy, normal cycling AAW (n = 15) and CW (n
      = 14) aged 19-34 years participated in the study. MAIN OUTCOME MEASURES: Hormone
      levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and
      FSH receptor mRNA expression in granulosa cells were measured. RESULTS: AAW had
      higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median
      (interquartile range); P < .001] and estrone [76.9 (36.6-173.4) vs 28.8 (22.5
      42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had
      lower FF androstenedione to estrone (7 +/- 1.8 vs 15.8 +/- 4.1; mean +/- SE; P =
      .04) and T to estradiol (0.01 +/- 0.002 vs 0.02 +/- 0.005; P = .03) ratios,
      indicating enhanced ovarian aromatase activity. There was a 5-fold increase in
      granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with
      no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH
      levels were not different in AAW and CW. CONCLUSIONS: Increased ovarian aromatase
      mRNA expression, higher FF estradiol levels, and decreased FF androgen to
      estrogen ratios in AAW compared with CW provide compelling evidence that racial
      differences in ovarian aromatase activity contribute to higher levels of
      estradiol in AAW across the menstrual cycle. The absence of differences in FSH,
      FSH receptor expression, and AMH suggest that population-specific genetic
      variation in CYP19, the gene encoding aromatase, or in factors affecting its
      expression should be sought.

PMID- 24285682
TI  - Identification of independent susceptible and protective HLA alleles in Japanese
      autoimmune thyroid disease and their epistasis.
AB  - BACKGROUND: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and
      Hashimoto thyroiditis (HT), which partially share immunological features.
      Determining the genetic basis that distinguishes GD and HT is a key to
      understanding the differences between these 2 related diseases. AIM: The aims of
      this study were to identify HLA antigens that can explain the immunopathological
      difference between GD and HT and to elucidate epistatic interactions between
      protective and susceptible HLA alleles, which can delineate the distinct function
      of HLA in AITD etiology. DESIGN: We genotyped 991 patients with AITD (547
      patients with GD and 444 patients with HT) and 481 control subjects at the HLA-A,
      HLA-C, HLA-B, DRB1, DQB1, and DPB1 loci. A direct comparison of HLA antigen
      frequencies between GD and HT was performed. We further analyzed an epistatic
      interaction between the susceptible and protective HLA alleles in the development
      of GD and HT. RESULTS: We identified 4 and 2 susceptible HLA molecules primarily
      associated with GD and HT, respectively, HLA-B*35:01, HLA-B*46:01, HLA
      DRB1*14:03, and HLA-DPB1*05:01 for GD and HLA-A*02:07 and HLA-DRB4 for HT. In a
      direct comparison between GD and HT, we identified GD-specific susceptible class
      II molecules, HLA-DP5 (HLA-DPB1*05:01; Pc = 1.0 * 10(-9)) and HLA-DR14 (HLA
      DRB*14:03; Pc = .0018). In contrast, HLA components on 3 common haplotypes in
      Japanese showed significant protective effects against the development of GD and
      HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02
      C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA
      A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and
      HT). Interestingly, the representative protective HLA, HLA-DR13 (HLA-DRB1*13:02),
      was epistatic to susceptible HLA-DP5 in controlling the development of GD.
      CONCLUSION: We show that HLA exerts a dual function, susceptibility and
      resistance, in controlling the development of GD and HT. We also show that the
      protective HLA allele is partially epistatic to the susceptible HLA allele in GD.

PMID- 24285683
TI  - Activating AKT2 mutation: hypoinsulinemic hypoketotic hypoglycemia.
AB  - BACKGROUND: Hyperinsulinemic hypoglycemia (HH), characterized by unregulated
      insulin secretion, is an important cause of persistent and severe hypoglycemia.
      The biochemical picture of HH is hypoketotic hypo-fatty-acidemic hypoglycemia
      along with elevated serum insulin. Not infrequently, serum insulin might be
      undetectable in HH despite the presence of evidence of insulin action (suppressed
      ketogenesis and lipolysis). However, autonomous activity of the downstream
      insulin signaling pathway without the presence of the ligand (insulin) will give
      rise to the same clinical and biochemical picture, apart from undetectable serum
      insulin/C-peptide. AKT2, a serine/threonine protein kinase, is involved
      downstream to the insulin receptor in mediating the physiological effects of
      insulin. AIM: We describe the second report of an activating AKT2 mutation
      leading to hypoinsulinemic hypoketotic hypoglycemia. PATIENTS AND METHODS: The
      proband presented with hemihypertrophy and symptomatic hypoglycemia.
      Investigations confirmed evidence of insulin action, despite absence of
      detectable serum insulin on multiple occasions. Molecular genetic testing for
      common causes of HH (ABCC8, KCNJ11, and GLUD1) was negative. Sequencing of AKT2
      identified a de novo mosaic c.49G->A (p.E17K) mutation, consistent with the
      clinical and biochemical phenotype. CONCLUSIONS: This is the second report of an
      activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypo-fatty
      acidemic hypoglycemia. In patients presenting a clinical and biochemical picture
      of HH with undetectable serum insulin, consideration of autonomous activation of
      the downstream insulin signaling pathway should be made.

PMID- 24285684
TI  - Lower expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is
      a hallmark of aldosterone-producing adenoma causing human primary aldosteronism.
AB  - CONTEXT: The molecular mechanisms of primary aldosteronism, a common cause of
      human hypertension, are unknown, but alterations of K(+) channels can play a key
      role. OBJECTIVE: The objective of the study was to investigate the following: 1)
      the expression of the Twik-related acid-sensitive K(+) channels (TASK) in
      aldosterone producing adenomas (APAs); 2) the role of TASK-2 in aldosterone
      synthesis; and 3) the determinants of TASK-2-blunted expression in APAs. DESIGN:
      We analyzed the transcriptome and the microRNA profiles of 32 consecutive APAs
      and investigated the protein expression and localization of TASK-2 in APA and
      adrenocortical cell lines (H295R and HAC15) using immunoblotting and confocal
      microscopy. The functional effect of TASK-2 blunted activity caused by a dominant
      negative mutation on steroidogenic enzymes, and aldosterone production was also
      assessed. TASK-2 regulation by selected microRNA was studied by a luciferase
      assay. RESULTS: TASK-2 was consistently less expressed at the transcript and
      protein levels in APAs than in the normal human adrenal cortex. H295R cell
      transfection with a TASK-2 dominant-negative mutant construct significantly
      increased the aldosterone production by 153% and the gene expression of
      aldosterone synthase (CYP11B2, gene expression fold change 3.1 vs control, P <
      .05) and the steroidogenic acute regulatory protein (gene expression fold change
      1.8 vs control, P < .05). Two microRNAs, hsa-miR-23 and hsa-miR-34, were found to
      decrease the TASK-2 expression by binding to the 3' untranslated region of the
      TASK-2 gene. CONCLUSIONS: The TASK-2 channel lower expression represents a
      hallmark of APA and is associated with a higher expression of hsa-miR-23 and hsa
      miR-34. The ensuing blunted TASK-2 activity increased the production of
      aldosterone in vitro and the expression of steroidogenic acute regulatory protein
      and CYP11B2. Hence, the lower expression of TASK-2 channel in APA cells can
      explain high aldosterone secretion in human primary aldosteronism despite the
      suppression of angiotensin II, hypertension, and hypokalemia.

PMID- 24285685
TI  - Genetic polymorphisms in 11beta-hydroxysteroid dehydrogenase type 1 correlate
      with the postdexamethasone cortisol levels and bone mineral density in patients
      evaluated for osteoporosis.
AB  - CONTEXT: Higher physiological cortisol levels may increase the risk of age
      related osteoporosis. We hypothesized that common polymorphisms in the cortisol
      synthesis enzyme 11beta-hydroxysteroid dehydrogenase (HSD11B) may cause
      interindividual variations in cortisol levels and age-related bone loss. STUDY
      DESIGN AND PATIENTS: We performed a retrospective study in a cohort of 452
      ambulatory patients under evaluation for osteoporosis. We investigated the
      associations of 16 single-nucleotide polymorphisms (in the HSD11B1 and HSD11B2
      genes with a postdexamethasone cortisol (PDC) level and bone mineral density
      (BMD; primary end points) and fracture risk (secondary end point) in a subgroup
      of 304 patients. The observed associations with BMD were validated in a subgroup
      of 148 patients. RESULTS: The PDC level increased with age (R = 0.274, P < 10(
      5), n = 287) and was negatively correlated with BMD at the femoral neck (R = 
      0.278, P < 10(-5), n = 258). Three genetically linked single-nucleotide
      polymorphisms (in intron 5 of HSD11B1), rs1000283, rs932335, and rs11811440, were
      significantly associated with BMD, with rs11811440 having the strongest
      association. The presence of the minor rs11811440 A allele was correlated with a
      lower PDC level (R = -0.128, P = .03, n = 304). The A allele was also
      consistently correlated with a higher spinal BMD in both patient subgroups (R =
      0.17, Bonferroni corrected P = .006, n = 452). The correlation with BMD remained
      significant after adjustment for age, gender, body mass index, and type of
      osteoporosis and was stronger in patients older than 65 years. CONCLUSION:
      Genetic variations in HSD11B1 may affect the physiological cortisol levels and
      the severity of age-related osteoporosis. Underlying functional mechanisms remain
      to be elucidated.

PMID- 24285687
TI  - Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and
      enhances cholesterol efflux capacity in subjects with hypercholesterolemia.
AB  - CONTEXT AND OBJECTIVE: Paraoxonase 1 (PON1), an enzyme associated with high
      density lipoprotein (HDL-PON1), is reported to have antioxidant and
      cardioprotective properties. The aim of the present study was to investigate the
      effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity
      in hypercholesterolemic subjects. DESIGN AND PARTICIPANTS: A total of 122
      hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or
      placebo (n = 61 of each group) for 24 weeks in a double-blind, randomized,
      placebo-controlled trial. Participants and investigators were masked to treatment
      allocation. RESULTS: Anthocyanin consumption significantly increased HDL
      cholesterol and decreased low -density lipoprotein cholesterol concentrations
      compared with placebo (P < .018 and P < .001, respectively). Anthocyanin
      supplementation also increased the activity of HDL-PON1 compared with placebo (P
      < .001). Furthermore, cholesterol efflux capacity was increased more in the
      anthocyanin group (20.0% increase) than in the placebo group (0.2% increase) (P <
      .001). The negative correlations established between HDL-PON1 activity and the
      levels of lipid hydroperoxides associated with HDL confirm the relationship
      between PON1 activity and lipid peroxidation of lipoproteins. Furthermore, a
      strong positive correlation was noted between increased HDL-PON1 activity and
      improved cholesterol efflux capacity both before and after adjustment for HDL
      cholesterol and apolipoprotein AI in anthocyanin-treated subjects (both P <
      .001). Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability
      of HDL and attenuated the cholesterol efflux capacity of subjects from
      anthocyanin group. CONCLUSIONS: Our observations suggest that the alterations of
      PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift
      to an improvement of cholesterol efflux capacity of HDL and may provide a link
      between anthocyanin and cardioprotective effects.

PMID- 24285686
TI  - Association between serum 25-hydroxyvitamin D level and subclinical
      cardiovascular disease in primary hyperparathyroidism.
AB  - CONTEXT: Vitamin D (25OHD) deficiency may be a modifiable cardiovascular (CV)
      risk factor. 25OHD insufficiency (20-29 ng/mL) and deficiency (<20 ng/mL) are
      common in primary hyperparathyroidism (PHPT), but their association with CV
      disease in PHPT has not been systematically investigated. OBJECTIVE: This study
      evaluated whether low 25OHD is associated with subclinical CV disease in PHPT.
      DESIGN: This is a cross-sectional analysis of PHPT patients with and without low
      25OHD. SETTINGS AND PARTICIPANTS: We studied 110 PHPT patients in a university
      hospital setting. OUTCOME MEASURES: We measured carotid intima-media thickness;
      carotid plaque presence/thickness; carotid strain and stiffness; left ventricular
      mass index; cardiac systolic and diastolic function; and mitral annular
      calcification. RESULTS: Low 25OHD levels (<30 ng/mL) were observed in 28%, but
      only 9% had 25OHD deficiency (<20 ng/mL). In the whole group, 25OHD levels
      negatively correlated with body mass index (r = -0.33, P = .0005), PTH (r = 
      0.30, P = .001), calcium (r = -0.29, P = .002), renal function, and PHPT
      duration. CV indices were normal except for carotid intima-media thickness,
      stiffness, and plaque thickness, which were increased, regardless of 25OHD
      status. Isovolumic relaxation time was the only CV measure associated with 25OHD
      (r = -0.26, P = .01). Those with 25OHD less than 20 ng/mL had more severe PHPT
      and a higher rate of nephrolithiasis. Those with 25OHD less than 30 ng/mL were
      younger, had higher body mass index, had lower serum phosphate, and were more
      likely to be male, nonwhite, and Hispanic. Other than lower tissue Doppler e' and
      higher isovolumic relaxation time within normal range in those with 25OHD less
      than 30 vs greater than 30 ng/mL, there were no differences in CV indices using
      either 25OHD threshold. CONCLUSIONS: Patients with mild PHPT have subclinical
      carotid abnormalities, but low 25OHD is not associated with abnormal carotid or
      cardiac measures. To the extent that PTH levels differentiated those with 25OHD
      less than 20 but not 30 ng/mL, these data support a 25OHD threshold of 20 ng/mL
      as clinically relevant in PHPT.

PMID- 24285688
TI  - Vitamin D deficiency predicts decline in kidney allograft function: a prospective
      cohort study.
AB  - CONTEXT: Vitamin D, often deficient in kidney transplant (KTx) recipients, has
      potential immunomodulatory effects. OBJECTIVE: This study aimed to evaluate
      whether vitamin D status affects the rate of decline in kidney allograft
      function. DESIGN, SETTING, AND PATIENTS: The study included a prospective cohort
      of 264 ambulatory KTx recipients at a single Japanese center. MAIN OUTCOME
      MEASURES: We measured the baseline 25-hydroxyvitamin D (25D) concentration and
      examined its association with annual decline in estimated glomerular filtration
      rate (eGFR). Secondary outcome was rescue treatment with iv methylprednisolone
      (IV-MP) as an index of rejection episodes. RESULTS: The mean serum 25D
      concentration was 17.1 (SD 6.5) ng/mL, and 68.4% patients had vitamin D
      inadequacy or deficiency. Time after KTx was a significant effect modifier for
      the association of serum 25D concentration with annual eGFR change and need for
      IV-MP (P for interaction < .1). We divided patients according to the median time
      after KTx (10 y) and found that low vitamin D was significantly associated with a
      rapid eGFR decline at less than 10 years after KTx but not at 10 or more years
      after KTx. The same was true for rescue treatment with IV-MP. Overall, propensity
      score matching showed independent associations of low vitamin D with both
      outcomes. Stratified matching confirmed pronounced associations at less than 10
      years after KTx. CONCLUSIONS: Vitamin D deficiency predicts a rapid decline in
      eGFR and need for IV-MP at less than 10 years after KTx. Future studies are
      warranted to evaluate the clinical efficacy of vitamin D supplementation.

PMID- 24285689
TI  - Lower-but-normal serum TSH level is associated with the development or
      progression of cognitive impairment in elderly: Korean Longitudinal Study on
      Health and Aging (KLoSHA).
AB  - CONTEXT: The association between subclinical hyperthyroidism and the risk of
      dementia has been validated in several studies. However, the effect of thyroid
      function within reference range on the risk of cognitive dysfunction including
      mild cognitive impairment (MCI) and dementia is still unclear. OBJECTIVE: Our aim
      was to investigate the association between thyroid function and the risk of MCI
      and dementia in euthyroid elderly subjects. DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a population-based prospective study as a part of the Korean
      Longitudinal Study on Health and Aging. A total of 313 participants who were
      euthyroid and nondemented at baseline and completed cognitive function tests at a
      5-year follow-up evaluation (mean age 72.5 +/- 6.9 y) were analyzed in the
      present study. MAIN OUTCOME MEASURE: Baseline thyroid function was compared
      according to the development of MCI or dementia during the study period. Binary
      logistic regression analysis was performed to investigate the independent
      association between thyroid function and cognitive impairment. RESULTS: At
      baseline evaluation, 237 subjects were cognitively normal, and 76 subjects had
      MCI. Diagnoses of cognitive function in 259 subjects remained unchanged or
      improved during the study period (nonprogression group), whereas 54 subjects
      showed progression of cognitive impairment to MCI or dementia (progression
      group). In the progression group, baseline serum TSH levels were lower than those
      in nonprogression group. Baseline serum free T4 levels were not significantly
      different between these two groups. The association between lower baseline serum
      TSH levels and the development of MCI or dementia was maintained after adjustment
      for conventional baseline risk factors. CONCLUSIONS: Lower serum TSH level within
      the reference range was independently associated with the risk of cognitive
      impairment including MCI and dementia in elderly subjects.

PMID- 24285690
TI  - Interacting inflammatory and growth factor signals underlie the obesity-cancer
      link.
AB  - The prevalence of obesity, an established risk factor for many chronic diseases
      (including diabetes, cardiovascular disease, stroke, and several types of
      cancer), has risen steadily for the past several decades in the United States and
      many parts of the world. Today, ~70% of U.S. adults and 30% of children are at an
      unhealthy weight. The evidence on key biologic mechanisms underlying the obesity
      cancer link, with an emphasis on local and systemic inflammatory processes and
      their crosstalk with energy-sensing growth factor signaling pathways, will be
      discussed. Understanding the influence and underlying mechanisms of obesity on
      chronic inflammation and cancer will identify promising mechanistic targets and
      strategies for disrupting the obesity-cancer link and provide important lessons
      regarding the associations between obesity, inflammation, and other chronic
      diseases. 

PMID- 24285691
TI  - Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced
      obesity and obesity-related metabolic disorders in mice.
AB  - We showed previously that dietary supplementation with oil from the marine
      zooplankton Calanus finmarchicus (Calanus oil) attenuates obesity, inflammation,
      and glucose intolerance in mice. More than 80% of Calanus oil consists of wax
      esters, i.e., long-chain fatty alcohols linked to long-chain fatty acids. In the
      present study, we compared the metabolic effects of Calanus oil-derived wax
      esters (WE) with those of purified eicosapentaenoic acid (EPA) + docosahexaenoic
      acid (DHA) ethyl esters (E/D) in a mouse model of diet-induced obesity. C57BL/6J
      mice received a high-fat diet (HFD; 45% energy from fat). After 7 wk, the diet
      was supplemented with either 1% (wt:wt) WE or 0.2% (wt:wt) E/D. The amount of EPA
      + DHA in the E/D diet was matched to the total amount of n-3 (omega-3)
      polyunsaturated fatty acids (PUFAs) in the WE diet. A third group was given an
      unsupplemented HFD throughout the entire 27-wk feeding period. WE reduced body
      weight gain, abdominal fat, and liver triacylglycerol by 21%, 34%, and 52%,
      respectively, and significantly improved glucose tolerance and aerobic capacity.
      In abdominal fat depots, WE reduced macrophage infiltration by 74% and
      downregulated expression of proinflammatory genes (tumor necrosis factor-alpha,
      interleukin-6, and monocyte chemoattractant protein-1), whereas adiponectin
      expression was significantly upregulated. By comparison, E/D primarily suppressed
      the expression of proinflammatory genes but had less influence on glucose
      tolerance than WE. E/D affected obesity parameters, aerobic capacity, or
      adiponectin expression by <10%. These results show that the wax ester component
      of Calanus oil can account for the biologic effects shown previously for the
      crude oil. However, these effects cannot exclusively be ascribed to the content
      of n-3 PUFAs in the wax ester fraction. 

PMID- 24285692
TI  - Dietary trans-10,cis-12 CLA reduces murine collagen-induced arthritis in a dose
      dependent manner.
AB  - Dietary trans-10,cis-12 (t10c12) conjugated linoleic acid (CLA) has been shown to
      reduce inflammation in a murine collagen-induced arthritis (CA) model. To
      understand the anti-inflammatory potential of t10c12-CLA in the diet, the minimum
      dose of pure dietary t10c12-CLA capable of reducing CA was investigated. Because
      plasma inflammatory cytokines often do not reflect the progression of late-stage
      arthritis, inflamed tissue cytokine concentrations were also investigated in
      relation to increasing dietary t10c12-CLA amounts. Mice were randomly assigned to
      the following dietary treatments upon the establishment of arthritis: corn oil
      (CO) or 0.125%, 0.25%, 0.375%, or 0.5% t10c12-CLA (wt:wt) for 84 d. Sham mice (no
      arthritis) were fed CO and served as controls. Arthritic paw score, based on
      subjective assessment of arthritic severity, and paw thickness decreased linearly
      overall [16-65% (P < 0.001) and 0.5-12% (P < 0.001), respectively] as dietary
      t10c12-CLA increased (P < 0.001, R(2) < 0.81). Increasing dietary t10c12-CLA was
      associated with a decrease in plasma interleukin (IL)-1beta at days 21 and 42
      compared with CO-fed arthritic mice, such that mice fed >=0.25% t10c12-CLA had IL
      1beta concentrations that were similar to sham mice. Plasma cytokines returned to
      sham mice concentrations by day 63 regardless of treatment; however, an arthritis
      induced elevation in paw IL-1beta decreased linearly as dietary t10c12-CLA
      concentrations increased at day 84 (P = 0.007, R(2) = 0.92). Similarly,
      increasing dietary t10c12-CLA linearly decreased paw tumor necrosis factor (TNF)
      alpha (P = 0.05, R(2) = 0.70). In conclusion, >=0.125% t10c12-CLA dose
      dependently reduced inflammation in a murine CA model. 

PMID- 24285694
TI  - Diversity of the structures in a distannene complex and its reduction to generate
      a six-membered Ti(2)Sn(4) ring complex.
AB  - In contrast to olefin complexes, their congeners of heavier elements display
      various coordination modes, and their complexes may be present as
      bis(metallylene) complexes, with side-on coordination, as metallacyclopropanes,
      or as pi complexes. In the course of our studies on the reactivity of
      dilithiostannoles towards transition-metal reagents, three-membered TiSn2 and six
      membered Ti2 Sn4 ring complexes were obtained. According to its geometric
      parameters, NMR analysis, and theoretical calculations, the TiSn2 complex cannot
      be categorized into any of these previously described bonding modes. Therefore, a
      novel resonance structure has been proposed for a complex that has a delocalized
      sigma-orbital over the TiSn2 ring to understand its electronic structure. The
      mechanism for the formation of the Ti2 Sn4 ring complex and its EPR spectrum are
      also discussed. 

PMID- 24285693
TI  - Propofol EC50 for inducing loss of consciousness is lower in the luteal phase of
      the menstrual cycle.
AB  - BACKGROUND: Varying levels of female sex hormones during the menstrual cycle were
      found to influence the central nervous system. The goal of the present study was
      to investigate whether the median (50%) effective effect-concentration (EC50) of
      propofol inducing loss of consciousness (LOC) varies between the luteal and the
      follicular phases of the menstrual cycle. METHODS: Twenty-two patients
      (follicular phase) and 20 patients (luteal phase) undergoing gynaecological
      procedures under general anaesthesia were enrolled on the study. Anaesthesia was
      conducted with a target-controlled infusion (TCI) of propofol. The initial target
      effect-site propofol concentration (Ceprop) was 3.5 ug ml(-1) and was adjusted
      stepwise by 0.5 ug ml(-1) at 4 min intervals by an up-down sequential method to
      reach LOC. Anaesthesia was maintained with a propofol TCI guided by the
      bispectral index. The correlation between female sex hormones and predicted
      Ceprop at the time of LOC was analysed and emergence time from anaesthesia was
      recorded. RESULTS: Propofol EC50 to induce LOC was higher in patients in the
      follicular phase than those in the luteal phase (4.17 vs 3.58 ug ml(-1), P<0.05).
      Progesterone correlated significantly with Ceprop at LOC. Emergence time was also
      longer in the follicular group than in the luteal group (6.5 vs 5.0 min, P<0.05).
      CONCLUSIONS: During general anaesthesia, patients in the luteal phase of the
      menstrual cycle had a lower propofol EC50 for LOC and a shorter emergence time
      compared with those in the follicular phase. Differences in progesterone levels
      between menstrual phases may contribute to these anaesthetic effects. Registry
      number of clinical trial ChiCTR-RCH-12002755.

PMID- 24285698
TI  - Health conditions and quality of life in survivors of childhood acute myeloid
      leukemia comparing post remission chemotherapy to BMT: a report from the
      children's oncology group.
AB  - BACKGROUND: Therapy for childhood acute myeloid leukemia (AML) has historically
      included chemotherapy with or without autologous bone marrow transplant (autoBMT)
      or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to
      compare health-related quality-of-life (HRQOL) outcomes between these treatment
      groups. PROCEDURE: Five-year survivors of AML diagnosed before age 21 and
      enrolled and treated from 1979 to 1995 on one of 4 national protocols were
      interviewed. These survivors or proxy caregivers completed a health questionnaire
      and an HRQOL measure. RESULTS: Of 180 survivors, 100 were treated with
      chemotherapy only, 26 with chemotherapy followed by autoBMT, and 54 with
      chemotherapy followed by alloBMT. Median age at interview was 20 years (range 8
      39). Twenty-one percent reported a severe or life-threatening chronic health
      condition (chemotherapy-only 16% vs. autoBMT 21% vs. alloBMT 33%; P = 0.02 for
      chemotherapy-only vs. alloBMT). Nearly all (95%) reported excellent, very good or
      good health. Reports of cancer-related pain and anxiety did not vary between
      groups. HRQOL scores among 136 participants >=14 years of age were similar among
      groups and to the normative population, though alloBMT survivors had a lower
      physical mean summary score (49.1 alloBMT vs. 52.2 chemotherapy-only; P = 0.03).
      Multivariate analyses showed the presence of severe chronic health conditions to
      be a strong predictor of physical but not mental mean summary scores.
      CONCLUSIONS: Overall HRQOL scores were similar among treatment groups, although
      survivors reporting more health conditions or cancer-related pain had diminished
      HRQOL. Attention to chronic health conditions and management of cancer-related
      pain may improve QOL.

PMID- 24285699
TI  - Facile access to cis-2,6-disubstituted tetrahydropyrans by palladium-catalyzed
      decarboxylative allylation: total syntheses of (+/-)-centrolobine and (+)
      decytospolides A and B.
AB  - cis-2,6-Tetrahydropyran is an important structural skeleton of bioactive natural
      products. A facile synthesis of cis-2,6-disubstituted-3,6-dihydropyrans as cis
      2,6-tetrahydropyran precursors has been achieved in high regio- and
      stereoselectivity with high yields. This reaction involves a palladium-catalyzed
      decarboxylative allylation of various 3,4-dihydro-2H-pyran substrates. Extending
      this reaction to 1,2-unsaturated carbohydrates allowed the achievement of
      challenging beta-C-glycosylation. Based on this methodology, the total syntheses
      of (+/-)-centrolobine and (+)-decytospolides A and B were achieved in concise
      steps and overall high yields. 

PMID- 24285701
TI  - Omuralide and vibralactone: differences in the proteasome- beta-lactone-gamma
      lactam binding scaffold alter target preferences.
AB  - Despite their structural similarity, the natural products omuralide and
      vibralactone have different biological targets. While omuralide blocks the
      chymotryptic activity of the proteasome with an IC50 value of 47 nM, vibralactone
      does not have any effect at this protease up to a concentration of 1 mM. Activity
      based protein profiling in HeLa cells revealed that the major targets of
      vibralactone are APT1 and APT2. 

PMID- 24285702
TI  - 1,2,3-Triazolo[4,5,-e]furazano[3,4,-b]pyrazine 6-oxide--a fused heterocycle with
      a roving hydrogen forms a new class of insensitive energetic materials.
AB  - The straightforward synthesis and energetic properties of a new class of
      energetic materials, 1,2,3-triazolo- [4,5-e]furazano[3,4-b]pyrazine 6-oxide and
      its energetic salts are described. They were characterized by IR and multinuclear
      NMR spectroscopy, elemental analysis, differential scanning calorimetry, and
      single-crystal X-ray diffraction are given. The X-ray structures show that in the
      title compound, the hydrogen atom is bonded to the nitrogen in the pyrazine ring;
      however, in the salts, the negative charge is associated with the triazole
      nitrogen. Heats of formation for all compounds were calculated with the G2 method
      and then combined with experimentally determined densities to obtain detonation
      pressures (P) and velocities (D) by using EXPLO5 program. These new materials
      exhibit good densities and thermal stabilities, high heats of formation,
      acceptable detonation properties, and are insensitive to impact. 

PMID- 24285703
TI  - Migratory and adhesive properties of Xenopus laevis primordial germ cells in
      vitro.
AB  - The directional migration of primordial germ cells (PGCs) to the site of gonad
      formation is an advantageous model system to study cell motility. The embryonic
      development of PGCs has been investigated in different animal species, including
      mice, zebrafish, Xenopus and Drosophila. In this study we focus on the physical
      properties of Xenopus laevis PGCs during their transition from the passive to the
      active migratory state. Pre-migratory PGCs from Xenopus laevis embryos at
      developmental stages 17-19 to be compared with migratory PGCs from stages 28-30
      were isolated and characterized in respect to motility and adhesive properties.
      Using single-cell force spectroscopy, we observed a decline in adhesiveness of
      PGCs upon reaching the migratory state, as defined by decreased attachment to
      extracellular matrix components like fibronectin, and a reduced adhesion to
      somatic endodermal cells. Data obtained from qPCR analysis with isolated PGCs
      reveal that down-regulation of E-cadherin might contribute to this weakening of
      cell-cell adhesion. Interestingly, however, using an in vitro migration assay, we
      found that movement of X. laevis PGCs can also occur independently of specific
      interactions with their neighboring cells. The reduction of cellular adhesion
      during PGC development is accompanied by enhanced cellular motility, as reflected
      in increased formation of bleb-like protrusions and inferred from electric cell
      substrate impedance sensing (ECIS) as well as time-lapse image analysis. Temporal
      alterations in cell shape, including contraction and expansion of the cellular
      body, reveal a higher degree of cellular dynamics for the migratory PGCs in
      vitro. 

PMID- 24285704
TI  - Maintenance of muscle myosin levels in adult C. elegans requires both the double
      bromodomain protein BET-1 and sumoylation.
AB  - Attenuation of RAS-mediated signalling is a conserved process essential to
      control cell proliferation, differentiation, and apoptosis. Cooperative
      interactions between histone modifications such as acetylation, methylation and
      sumoylation are crucial for proper attenuation in C. elegans, implying that the
      proteins recognising these histone modifications could also play an important
      role in attenuation of RAS-mediated signalling. We sought to systematically
      identify these proteins and found BET-1. BET-1 is a conserved double bromodomain
      protein that recognises acetyl-lysines on histone tails and maintains the stable
      fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are
      depleted of muscle myosin, an essential component of myofibrils. We also show
      that this muscle myosin depletion does not occur in all animals at a specific
      time, but rather that the penetrance of the phenotype increases with age. To gain
      mechanistic insights into this process, we sought to delay the occurrence of the
      muscle myosin depletion phenotype and found that it requires caspase activity and
      MEK-dependent signalling. We also performed transcription profiling on these
      mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase
      receptor acting upstream of MEK. Consistent with a MEK requirement, we could
      delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus,
      this work uncovered a caspase- and MEK-dependent mechanism that acts specifically
      on ageing adults to maintain the appropriate net level of muscle myosin. 

PMID- 24285705
TI  - Does an instrumented treadmill correctly measure the ground reaction forces?
AB  - Since the 1990s, treadmills have been equipped with multi-axis force transducers
      to measure the three components of the ground reaction forces during walking and
      running. These measurements are correctly performed if the whole treadmill
      (including the motor) is mounted on the transducers. In this case, the
      acceleration of the treadmill centre of mass relative to the reference frame of
      the laboratory is nil. The external forces exerted on one side of the treadmill
      are thus equal in magnitude and opposite in direction to the external forces
      exerted on the other side. However, uncertainty exists about the accuracy of
      these measures: due to friction between the belt and the tread-surface, due to
      the motor pulling the belt, some believe that it is not possible to correctly
      measure the horizontal components of the forces exerted by the feet on the belt.
      Here, we propose a simple model of an instrumented treadmill and we demonstrate
      (1) that the forces exerted by the subject moving on the upper part of the
      treadmill are accurately transmitted to the transducers placed under it and (2)
      that all internal forces - including friction - between the parts of the
      treadmill are cancelling each other. 

PMID- 24285706
TI  - Evaluation of visible implant elastomer tags in zebrafish (Danio rerio).
AB  - The use of the visible implant elastomer (VIE) tagging system in zebrafish (Danio
      rerio) was examined. Two tag orientations (horizontal and vertical) at the dorsal
      fin base were tested for tag retention, tag fragmentation and whether VIE tags
      affected growth and survival of juvenile zebrafish (1-4 month post hatch). Six
      tag locations (abdomen, anal fin base, caudal peduncle, dorsal fin base, pectoral
      fin base, isthmus) and 5 tag colors (yellow, red, pink, orange, blue) were
      evaluated for ease of VIE tag application and tag visibility in adult zebrafish.
      Long-term retention (1 year) and multiple tagging sites (right and left of dorsal
      fin and pectoral fin base) were examined in adult zebrafish. Lastly, survival of
      recombination activation gene 1(-/-) (rag1(-/-)) zebrafish was evaluated after
      VIE tagging. The best tag location was the dorsal fin base, and the most visible
      tag color was pink. Growth rate of juvenile zebrafish was not affected by VIE
      tagging. Horizontal tagging is recommended in early stages of fish growth (1-2
      months post hatch). VIE tags were retained for 1 year and tagging did not
      interfere with long-term growth and survival. There was no mortality associated
      with VIE tagging in rag1(-/-) zebrafish. The VIE tagging system is highly
      suitable for small-sized zebrafish. When familiar with the procedure, 120 adult
      zebrafish can be tagged in one hour. It does not increase mortality in adult
      zebrafish or interfere with growth in juvenile or adult zebrafish. 

PMID- 24285707
TI  - Characterization of the male ApcMin/+ mouse as a hypogonadism model related to
      cancer cachexia.
AB  - Cancer cachexia, the unintentional loss of lean body mass, is associated with
      decreased quality of life and poor patient survival. Hypogonadism, involving a
      reduction in circulating testosterone, is associated with the cachectic
      condition. At this time there is a very limited understanding of the role of
      hypogonadism in cancer cachexia progression. This gap in our knowledge is related
      to a lack of functional hypogonadal models associated with cancer cachexia. The
      Apc(Min/+) mouse is an established colorectal cancer model that develops an IL-6
      dependent cachexia which is physiologically related to human disease due to the
      gradual progression of tumor development and cachexia. The purpose of this study
      was to assess the utility of the Apc(Min/+) mouse for the examination of
      hypogonadism during cancer cachexia and to investigate if IL-6 has a role in this
      process. We report that Apc(Min/+) mice that are weight stable have comparable
      testosterone levels and gonad size compared to wild type mice. Cachectic
      Apc(Min/+) mice exhibit a reduction in circulating testosterone and gonad size,
      which has a significant association with the degree of muscle mass and functional
      strength loss. Circulating testosterone levels were also significantly associated
      with the suppression of myofibrillar protein synthesis. Skeletal muscle and
      testes androgen receptor expression were decreased with severe cachexia. Although
      testes STAT3 phosphorylation increased with severe cachexia, systemic IL-6 over
      expression for 2 weeks was not sufficient to reduce either testes weight or
      circulating testosterone. Inhibition of systemic IL-6 signaling by an IL-6
      receptor antibody to Apc(Min/+) mice that had already initiated weight loss was
      sufficient to attenuate a reduction in testes size and circulating testosterone.
      In summary, the Apc(Min/+) mouse becomes hypogonadal with the progression of
      cachexia severity and elevated circulating IL-6 levels may have a role in the
      development of hypogonadism during cancer cachexia. 

PMID- 24285708
TI  - Activation of Drosophila hemocyte motility by the ecdysone hormone.
AB  - Drosophila hemocytes compose the cellular arm of the fly's innate immune system.
      Plasmatocytes, putative homologues to mammalian macrophages, represent ~95% of
      the migratory hemocyte population in circulation and are responsible for the
      phagocytosis of bacteria and apoptotic tissues that arise during metamorphosis.
      It is not known as to how hemocytes become activated from a sessile state in
      response to such infectious and developmental cues, although the hormone ecdysone
      has been suggested as the signal that shifts hemocyte behaviour from quiescent to
      migratory at metamorphosis. Here, we corroborate this hypothesis by showing the
      activation of hemocyte motility by ecdysone. We induce motile behaviour in larval
      hemocytes by culturing them with 20-hydroxyecdysone ex vivo. Moreover, we also
      determine that motile cell behaviour requires the ecdysone receptor complex and
      leads to asymmetrical redistribution of both actin and tubulin cytoskeleton. 

PMID- 24285709
TI  - Comparison of TALEN scaffolds in Xenopus tropicalis.
AB  - Transcription activator-like effector nucleases (TALENs) are facile and potent
      tools used to modify a gene of interest for targeted gene knockout. TALENs
      consist of an N-terminal domain, a DNA-binding domain, and a C-terminal domain,
      which are derived from a transcription activator-like effector, and the non
      specific nuclease domain of FokI. Using Xenopus tropicalis (X. tropicalis), we
      compared the toxicities and somatic mutation activities of four TALEN
      architectures in a side-by-side manner: a basic TALEN, a scaffold with the same
      truncated N- and C-terminal domains as GoldyTALEN, a scaffold with the truncated
      N- and C-terminal domains and an obligate heterodimeric nuclease domain, and a
      scaffold with the truncated N- and C-terminal domains and an obligate
      heterodimeric Sharkey nuclease domain. The strongest phenotype and targeted
      somatic gene mutation were induced by the injection of TALEN mRNAs containing the
      truncated N- and C-terminal domains and an obligate heterodimeric nuclease
      domain. The obligate heterodimeric TALENs exhibited reduced toxicity compared to
      the homodimeric TALENs, and the homodimeric GoldyTALEN-type scaffold showed both
      a high activity of somatic gene modification and high toxicity. The Sharkey
      mutation in the heterodimeric nuclease domain reduced the TALEN-mediated somatic
      mutagenesis. 

PMID- 24285710
TI  - Mechanisms of palmitate-induced cell death in human osteoblasts.
AB  - Lipotoxicity is an overload of lipids in non-adipose tissues that affects
      function and induces cell death. Lipotoxicity has been demonstrated in bone cells
      in vitro using osteoblasts and adipocytes in coculture. In this condition,
      lipotoxicity was induced by high levels of saturated fatty acids (mostly
      palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the
      present study, we aimed to identify the underlying mechanisms of lipotoxicity in
      human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was
      preceded by the activation of autophagosomes that surround palmitate droplets.
      Palmitate also induced apoptosis though the activation of the Fas/Jun kinase
      (JNK) apoptotic pathway. In addition, osteoblasts could be protected from
      lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3
      methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In
      summary, we have identified two major molecular mechanisms of lipotoxicity in
      osteoblasts and in doing so we have identified a new potential therapeutic
      approach to prevent osteoblast dysfunction and death, which are common features
      of age-related bone loss and osteoporosis. 

PMID- 24285711
TI  - Comparative visual ecophysiology of mid-Atlantic temperate reef fishes.
AB  - The absolute light sensitivities, temporal properties, and spectral sensitivities
      of the visual systems of three mid-Atlantic temperate reef fishes (Atlantic
      spadefish [Ephippidae: Chaetodipterus faber], tautog [Labridae: Tautoga onitis],
      and black sea bass [Serranidae: Centropristis striata]) were studied via
      electroretinography (ERG). Pelagic Atlantic spadefish exhibited higher temporal
      resolution but a narrower dynamic range than the two more demersal foragers. The
      higher luminous sensitivities of tautog and black sea bass were similar to other
      benthic and demersal coastal mid-Atlantic fishes. Flicker fusion frequency
      experiments revealed significant interspecific differences at maximum intensities
      that correlated with lifestyle and habitat. Spectral responses of the three
      species spanned 400-610&emsp14;nm, with high likelihood of cone dichromacy
      providing the basis for color and contrast discrimination. Significant day-night
      differences in spectral responses were evident in spadefish and black sea bass
      but not tautog, a labrid with characteristic structure-associated nocturnal
      torpor. Atlantic spadefish responded to a wider range of wavelengths than did
      deeper-dwelling tautog or black sea bass. Collectively, these results suggest
      that temperate reef-associated fishes are well-adapted to their gradient of
      brighter to dimmer photoclimates, representative of their unique ecologies and
      life histories. Continuing anthropogenic degradation of water quality in coastal
      environments, at a pace faster than the evolution of visual systems, may however
      impede visual foraging and reproductive signaling in temperate reef fishes. 

PMID- 24285712
TI  - Late-replicating CNVs as a source of new genes.
AB  - Asynchronous replication of the genome has been associated with different rates
      of point mutation and copy number variation (CNV) in human populations. Here, our
      aim was to investigate whether the bias in the generation of CNV that is
      associated with DNA replication timing might have conditioned the birth of new
      protein-coding genes during evolution. We show that genes that were duplicated
      during primate evolution are more commonly found among the human genes located in
      late-replicating CNV regions. We traced the relationship between replication
      timing and the evolutionary age of duplicated genes. Strikingly, we found that
      there is a significant enrichment of evolutionary younger duplicates in late
      replicating regions of the human and mouse genome. Indeed, the presence of
      duplicates in late-replicating regions gradually decreases as the evolutionary
      time since duplication extends. Our results suggest that the accumulation of
      recent duplications in late-replicating CNV regions is an active process
      influencing genome evolution. 

PMID- 24285713
TI  - The snRNA-processing complex, Integrator, is required for ciliogenesis and dynein
      recruitment to the nuclear envelope via distinct mechanisms.
AB  - We previously reported that the small nuclear RNA processing complex, Integrator,
      is required for dynein recruitment to the nuclear envelope at mitotic onset in
      cultured human cells. We now report an additional role for INT in ciliogenesis.
      Depletion of INT subunits from cultured human cells results in loss of primary
      cilia. We provide evidence that the requirements for INT in dynein localization
      and ciliogenesis are uncoupled: proteins essential for ciliogenesis are not
      essential for dynein recruitment to the nuclear envelope, while depletion of
      known regulators of perinuclear dynein has minimal effects on ciliogenesis. Taken
      together, our data support a model in which INT ensures proper processing of
      distinct pools of transcripts encoding components that independently promote
      perinuclear dynein enrichment and ciliogenesis. 

PMID- 24285715
TI  - Effects of the electric field on the properties of ZnO-graphene composites: a
      density functional theory study.
AB  - In this work, the effects of the electric field on the properties of ZnO-graphene
      composites were theoretically studied using density functional theory
      calculations. Three types of ZnO-graphene composites including composites of
      pristine graphene, graphene with defects as well as graphene oxide and a ZnO
      bilayer were studied. We calculated and analyzed the binding energies, charge
      transfer, band structures and work functions of the above composites under the
      external electric fields. The DFT calculation results demonstrate that the
      binding energies are sensitive to the electric field, and increasing the external
      electric field gives rise to stronger binding energies. The extent of charge
      transfer is correlated with the magnitude of the external electric field, but the
      band gaps are hardly affected by the external electric field. The work functions
      vary depending on the different structures of the composites and surface sides,
      and they are also tunable by the external electric field. 

PMID- 24285714
TI  - Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc
      regulation.
AB  - Cancer cells frequently depend on chromatin regulatory activities to maintain a
      malignant phenotype. Here, we show that leukemia cells require the mammalian
      SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal
      potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor
      formation in several cell types, we found that leukemia cells instead rely on
      Brg1 to support their oncogenic transcriptional program, which includes Myc as
      one of its key targets. To account for this context-specific function, we
      identify a cluster of lineage-specific enhancers located 1.7 Mb downstream from
      Myc that are occupied by SWI/SNF as well as the BET protein Brd4. Brg1 is
      required at these distal elements to maintain transcription factor occupancy and
      for long-range chromatin looping interactions with the Myc promoter. Notably,
      these distal Myc enhancers coincide with a region that is focally amplified in
      ~3% of acute myeloid leukemias. Together, these findings define a leukemia
      maintenance function for SWI/SNF that is linked to enhancer-mediated gene
      regulation, providing general insights into how cancer cells exploit
      transcriptional coactivators to maintain oncogenic gene expression programs. 

PMID- 24285716
TI  - Low doses of bovine somatotropin enhance conceptus development and fertility in
      lactating dairy cows.
AB  - Objectives were to evaluate the effects of administering either one or two low
      doses of slow-release recombinant bovine somatotropin (bST) on hormone
      concentrations, conceptus development, and fertility in dairy cows. Cows from two
      farms were detected in estrus on or after 50 days postpartum (n = 1483),
      inseminated, and enrolled in the study (Day 0). Within farm, cows were blocked by
      parity and assigned randomly to receive a single placebo injection at
      insemination (control), a single injection with 325 mg of bST at insemination (S
      bST), or two injections with 325 mg of bST administered on Days 0 and 14 (T-bST).
      From a subset of cows, blood was collected twice weekly from Day 0 to 42 for
      determination of hormone concentrations and on Day 19 for isolation of leucocytes
      and analysis of transcript abundance of selected interferon-stimulated genes.
      Pregnancy was diagnosed on Days 31 and 66, and ultrasonographic morphometry of
      the conceptus was performed on Days 34 and 48 in a subset of cows. Cows that
      received T-bST had increased plasma concentrations of GH and IGF1 for 4 wk,
      increased mRNA expression of ISG15 and RTP4 in leukocytes, earlier rise in the
      pregnancy-specific protein B in plasma of pregnant cows, increased conceptus
      size, and enhanced fertility. Cows that received S-bST had increased
      concentrations of GH and IGF1 for only 2 wk and it was insufficient to alter
      conceptus development and fertility. In conclusion, supplementation with low
      doses of bST during the pre- and peri-implantation periods enhanced conceptus
      development, reduced embryonic losses, and improved fertility in dairy cows. 

PMID- 24285717
TI  - Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats
      treated with a nonsteroidal negative allosteric modulator of follicle-stimulating
      hormone receptor.
AB  - We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623)
      that blocked FSH-induced cAMP and progesterone production but did not block
      estradiol production. That FSHR NAM did not affect FSH-induced preovulatory
      follicle development as evidenced by the lack of an effect on the number of FSH
      dependent oocytes found in the ampullae following ovulation with hCG. A goal is
      the development of a nonsteroidal contraceptive. Toward this end, a high
      throughput screen using human FSHR identified an additional nonsteroidal small
      molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting
      production of cAMP and progesterone, it also inhibited FSH-induced estradiol in
      an in vitro rat granulosa primary cell culture bioassay. When immature,
      noncycling female rats were injected subcutaneously or by oral dosing prior to
      exogenous FSH administration, it was found that ADX68692 decreased the number of
      oocytes recovered from the ampullae. The estrous cycles of mature female rats
      were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg
      ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with
      mature males had implantation sites compared to 33% in the 10 mg/kg group and 77%
      in the control group. A surprising finding was that a structural analog ADX68693,
      while effectively blocking progesterone production with similar efficacy as
      ADX68692, did not block estrogen production and despite better oral availability
      did not decrease the number of oocytes found in the ampullae even when used at
      100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR,
      nonsteroidal contraception requires that both arms of the FSHR steroidogenic
      pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a
      corollary to these findings is that it seems reasonable to propose that the
      estrogen-dependent diseases such as endometriosis may benefit from inhibition of
      FSH action at the ovary using the FSHR NAM approach. 

PMID- 24285718
TI  - Nondividing, postpubertal rat sertoli cells resumed proliferation after
      transplantation.
AB  - Conventionally, it was believed that Sertoli cells (SC) stopped proliferating at
      puberty and became terminally differentiated quiescent cells. However, recent
      studies have challenged that dogma. In this study, we transplanted nondividing SC
      isolated from 23- to 27-day-old postpubertal rats transduced with a recombinant
      adenoviral vector (containing furin-modified human proinsulin cDNA) into diabetic
      severe combined immunodeficiency mice. Immunostaining the grafts for cell
      proliferation markers, proliferating cell nuclear antigen (PCNA) and MKI67,
      revealed that transplanted SC within the grafts were proliferating. Possible
      causes for resumption of proliferation of SC could be viral transduction, cell
      isolation and culture, higher abdominal temperature at the transplant site,
      and/or transplantation. To test for these possible causes, double-
      immunofluorescence staining was performed for GATA4 (SC marker) and MKI67. None
      of the SC were positive for MKI67 in tissue collected during SC isolation and
      culture or at higher temperature. However, nontransduced SC stained positive for
      MKI67 after transplantation into rats, suggesting viral transduction was not a
      key factor for induction of SC proliferation. Interestingly, resumption in
      proliferative ability of nondividing SC was temporary, as SC stopped
      proliferating within 14 days of transplantation and did not proliferate
      thereafter. Quantification of 5-bromo-2'-deoxyuridine-labeled SC demonstrated
      that 7%-9% of the total transplanted SC were proliferating in the grafts. These
      data indicate for the first time that nondividing SC resumed proliferation after
      transplantation and further validate previous findings that SC are not terminally
      differentiated. Hence, transplantation of SC could provide a useful model with
      which to study the regulation of SC proliferation in vivo. 

PMID- 24285719
TI  - Polyinosinic-polycytidylic acid initiates ovarian innate antiviral response and
      inhibits steroidogenesis in female mice.
AB  - Viral infection may perturb ovarian functions. However, innate antiviral response
      in the ovary has not been intensively investigated. In this study, we examined
      the innate antiviral system in the mouse ovary and the impacts of antiviral
      response on steroidogenesis. Major virus sensors, including Toll-like receptor 3
      (TLR3), retinoic acid-inducible gene I, and melanoma differentiation-associated
      gene 5, are predominantly expressed in ovarian stromal and granulosa cells.
      Polyinosinic-polycytidylic acid (poly [I:C]) is a common agonist of TLR3,
      retinoic acid-inducible gene I, and melanoma differentiation-associated gene 5.
      Intraperitoneal injection of poly (I:C) activated nuclear factor kappa B and
      interferon (IFN) regulatory factor 3 in the ovarian cells and induced the
      expression of proinflammatory cytokines, including tumor necrosis factor alpha,
      interleukin 6, and type 1 IFNs (IFNA/B). Moreover, poly (I:C) upregulated the
      expression of several antiviral proteins, including 2'-5'-oligoadenylate
      synthetase, IFN-stimulated gene 15, and Mx GTPase 1. The innate antiviral
      response in the ovary was significantly reduced in Tlr3-deficient mice. Notably,
      we demonstrated that poly (I:C) injection inhibits steroidogenesis enzyme
      expression and decreases plasma estradiol and testosterone levels. The results
      show that the mouse ovary is equipped with innate antiviral state, and the
      antiviral response perturbs ovarian endocrine function. 

PMID- 24285720
TI  - Inhibitory effect of progesterone on cervical tissue formation in a three
      dimensional culture system with human cervical fibroblasts.
AB  - Progesterone supplementation is recommended to prevent preterm birth in women
      with a short cervix, but the mechanism is unclear. We hypothesize that
      progesterone acts by altering the composition of the cervical extracellular
      matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both
      two-dimensional (2D) and three-dimensional (3D) cultures. For 2D culture, cells
      were seeded in 6-well plates and cultured with media supplemented with estradiol
      (10(-8) M), progesterone (10(-7) or 10(-6) M), and vehicle. For 3D culture, the
      cells were cultured on a porous silk protein scaffold system. Progesterone and
      estrogen receptors were documented by immunohistochemistry and Western blot
      analysis. In both 2D and 3D cultures, decreased collagen synthesis was seen with
      increased progesterone concentration. Three-dimensional cultures could be
      maintained significantly longer than 2D cultures, and the morphology of 3D
      cultures appeared similar to native cervical tissue. Thus, further studies were
      performed in 3D culture. To determine the effect of progesterone concentration,
      the 3D scaffolds were cultured with estradiol (10(-8) M) and five conditions:
      vehicle; 10(-9), 10(-8), or 10(-7) M progesterone; or 10(-7) M progesterone plus
      10(-6) M mifepristone. The highest progesterone concentration correlated with the
      least amount of collagen synthesis. Collagen synthesis progressively increased as
      progesterone concentration decreased. This effect was partially antagonized by
      mifepristone, suggesting the mechanism is mediated by the progesterone receptor.
      This hormonally responsive 3D culture system supports the hypothesis that
      progesterone has a direct effect on remodeling cervical ECM during pregnancy. The
      3D culture system could be useful for studying the mechanism of progesterone
      effects on the cervix. 

PMID- 24285721
TI  - Canonical nucleosome organization at promoters forms during genome activation.
AB  - The organization of nucleosomes influences transcriptional activity by
      controlling accessibility of DNA binding proteins to the genome. Genome-wide
      nucleosome binding profiles have identified a canonical nucleosome organization
      at gene promoters, where arrays of well-positioned nucleosomes emanate from
      nucleosome-depleted regions. The mechanisms of formation and the function of
      canonical promoter nucleosome organization remain unclear. Here we analyze the
      genome-wide location of nucleosomes during zebrafish embryogenesis and show that
      well-positioned nucleosome arrays appear on thousands of promoters during the
      activation of the zygotic genome. The formation of canonical promoter nucleosome
      organization is independent of DNA sequence preference, transcriptional
      elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical
      promoter nucleosome organization correlates with the presence of histone H3
      lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation.
      These findings reveal that genome activation is central to the organization of
      nucleosome arrays during early embryogenesis. 

PMID- 24285722
TI  - Natural variation in the histone demethylase, KDM4C, influences expression levels
      of specific genes including those that affect cell growth.
AB  - DNA sequence variants influence gene expression and cellular phenotypes. In this
      study, we focused on natural variation in the gene encoding the histone
      demethylase, KDM4C, which promotes transcriptional activation by removing the
      repressive histone mark, H3K9me3, from its target genes. We uncovered cis-acting
      variants that contribute to extensive individual differences in KDM4C expression.
      We also identified the target genes of KDM4C and demonstrated that variation in
      KDM4C expression leads to differences in the growth of normal and some cancer
      cells. Together, our results from genetic mapping and molecular analysis provide
      an example of how genetic variation affects epigenetic regulation of gene
      expression and cellular phenotype. 

PMID- 24285723
TI  - Monitoring chemotherapeutic response by hyperpolarized 13C-fumarate MRS and
      diffusion MRI.
AB  - Targeted chemotherapeutic agents often do not result in tumor shrinkage, so new
      biomarkers that correlate with clinical efficacy are needed. In this study, we
      investigated noninvasive imaging protocols to monitor responses to sorafenib, a
      multikinase inhibitor approved for treatment of renal cell and hepatocellular
      carcinoma. Healthy cells are impermeable to fumarate, so conversion of this
      metabolite to malate as detected by (13)C-magnetic resonance spectroscopy (MRS)
      has been suggested as one marker for cell death and treatment response in tumors.
      Diffusion MRI also has been suggested as a measure of therapy-induced cytotoxic
      edema because viable cells act as a diffusion barrier in tissue. For these
      reasons, we assessed sorafenib responses using hyperpolarized (13)C-fumarate,
      diffusion-weighted MRI (DW-MRI) in a xenograft model of human breast cancer in
      which daily administration of sorafenib was sufficient to stabilize tumor growth.
      We detected signals from fumarate and malate following intravenous administration
      of hyperpolarized fumarate with a progressive increase in the malate-to-fumarate
      (MA/FA) ratio at days 2 to 5 after sorafenib infusion. The apparent diffusion
      coefficient (ADC) measured by DW-MRI increased in the treated group consistent
      with cytotoxic edema. However, the MA/FA ratio was a more sensitive marker of
      therapeutic response than ADC, with 2.8-fold versus 1.3-fold changes,
      respectively, by day 5 of drug treatment. Histologic analyses confirmed cell
      death in the sorafenib-treated cohort. Notably, (13)C-pyruvate-to-lactate
      conversion was not affected by sorafenib in the breast cancer model examined. Our
      results illustrate how combining hyperpolarized substrates with DW-MRI can allow
      noninvasive monitoring of targeted therapeutic responses at relatively early
      times after drug administration.

PMID- 24285724
TI  - Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in
      bladder cancer as monitored longitudinally by PET imaging.
AB  - Targeted therapies have yet to have significant impact on the survival of
      patients with bladder cancer. In this study, we focused on the urea cycle enzyme
      argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer,
      based on our discovery of the prognostic and functional import of ASS1 in this
      setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295
      Asian patients was analyzed, along with its hypothesized prognostic impact and
      association with clinicopathologic features, including tumor size and invasion.
      Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss
      were investigated in urothelial cancer cells. We detected ASS1 negativity in 40%
      of bladder cancers, in which multivariate analysis indicated worse disease
      specific and metastasis-free survival. ASS1 loss secondary to epigenetic
      silencing was accompanied by increased tumor cell proliferation and invasion,
      consistent with a tumor-suppressor role for ASS1. In developing a treatment
      approach, we identified a novel targeted antimetabolite strategy to exploit
      arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a
      therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells
      and its exposure was associated with a marked reduction in intracellular levels
      of thymidine, due to suppression of both uptake and de novo synthesis. We found
      that thymidine uptake correlated with thymidine kinase-1 protein levels and that
      thymidine levels were imageable with [(18)F]-fluoro-L-thymidine (FLT)-positron
      emission tomography (PET). In contrast, inhibition of de novo synthesis was
      linked to decreased expression of thymidylate synthase and dihydrofolate
      reductase. Notably, inhibition of de novo synthesis was associated with
      potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken
      together, our findings argue that arginine deprivation combined with antifolates
      warrants clinical investigation in ASS1-negative urothelial and related cancers,
      using FLT-PET as an early surrogate marker of response.

PMID- 24285725
TI  - p53-induced miR-15a/16-1 and AP4 form a double-negative feedback loop to regulate
      epithelial-mesenchymal transition and metastasis in colorectal cancer.
AB  - The transcription factor AP4 mediates epithelial-mesenchymal transition (EMT) in
      colorectal cancer but its control in this setting is not fully understood. Here,
      we report the definition of a double-negative feedback loop involving AP4 and miR
      15a/16-1 that regulates EMT and metastatic progression. In colorectal cancer
      cells, AP4 was downregulated by DNA damage in a p53-dependent manner. AP4
      downregulation by p53 was mediated indirectly by the tumor-suppressive microRNAs
      miR-15a and miR-16-1, which targeted the 3' untranslated region (3'-UTR) of AP4
      mRNA, induced mesenchymal-epithelial transition (MET), and inhibited colorectal
      cancer cell migration and invasion. The downregulation of AP4 was necessary for
      induction of MET and cell cycle arrest by miR-15a/16-1. In tumor xenoplants,
      ectopic miR-15a/16-1 suppressed formation of lung metastases. Furthermore, AP4
      directly suppressed expression of miR-15a/16-1. In clinical specimens of
      colorectal cancer, miR-15a levels inversely correlated with AP4 protein levels
      shown previously to correlate with distant metastasis and poor survival. In
      summary, our results define a double-negative feedback loop involving miR-15a/16
      1 and AP4 that stabilizes epithelial and mesenchymal states, respectively, which
      may determine metastatic prowess.

PMID- 24285726
TI  - IRP2 regulates breast tumor growth.
AB  - Experimental and epidemiologic evidence suggests that dysregulation of proteins
      involved in iron metabolism plays a critical role in cancer. The mechanisms by
      which cancer cells alter homeostatic iron regulation are just beginning to be
      understood. Here, we demonstrate that iron regulatory protein 2 (IRP2) plays a
      key role in iron accumulation in breast cancer. Although both IRP1 and IRP2 are
      overexpressed in breast cancer, the overexpression of IRP2, but not IRP1, is
      associated with decreased ferritin H and increased transferrin receptor 1 (TfR1).
      Knockdown of IRP2 in triple-negative MDA-MB-231 human breast cancer cells
      increases ferritin H expression and decreases TfR1 expression, resulting in a
      decrease in the labile iron pool. Further, IRP2 knockdown reduces growth of MDA
      MB-231 cells in the mouse mammary fat pad. Gene expression microarray profiles of
      patients with breast cancer demonstrate that increased IRP2 expression is
      associated with high-grade cancer. Increased IRP2 expression is observed in
      luminal A, luminal B, and basal breast cancer subtypes, but not in breast tumors
      of the ERBB2 molecular subtype. These results suggest that dysregulation of IRP2
      is an early nodal point underlying altered iron metabolism in breast cancer and
      may contribute to poor outcome of some patients with breast cancer.

PMID- 24285727
TI  - Preclinical therapeutic efficacy of a novel pharmacologic inducer of apoptosis in
      malignant peripheral nerve sheath tumors.
AB  - Neurofibromatosis type I (NF1) is an autosomal disorder that affects neural crest
      derived tissues, leading to a wide spectrum of clinical presentations. Patients
      commonly present with plexiform neurofibromas, benign but debilitating growths
      that can transform into malignant peripheral nerve sheath tumors (MPNST), a main
      cause of mortality. Currently, surgery is the primary course of treatment for
      MPNST, but with the limitation that these tumors are highly invasive.
      Radiotherapy is another treatment option, but is undesirable because it can
      induce additional mutations. Patients with MPNST may also receive doxorubicin as
      therapy, but this DNA-intercalating agent has relatively low tumor specificity
      and limited efficacy. In this study, we exploited a robust genetically engineered
      mouse model of MPNST that recapitulates human NF1-associated MPNST to identify a
      novel small chemical compound that inhibits tumor cell growth. Compound 21
      (Cpd21) inhibits growth of all available in vitro models of MPNST and human MPNST
      cell lines, while remaining nontoxic to normally dividing Schwann cells or mouse
      embryonic fibroblasts. We show that this compound delays the cell cycle and leads
      to cellular apoptosis. Moreover, Cpd21 can reduce MPNST burden in a mouse
      allograft model, underscoring the compound's potential as a novel
      chemotherapeutic agent.

PMID- 24285729
TI  - Compensatory functions and interdependency of the DNA-binding domain of BRCA2
      with the BRCA1-PALB2-BRCA2 complex.
AB  - BRCA1, BRCA2, and PALB2 are key players in cellular tolerance to chemotherapeutic
      agents, including camptothecin, cisplatin, and PARP inhibitor. The N-terminal
      segment of BRCA2 interacts with PALB2, thus contributing to the formation of the
      BRCA1-PALB2-BRCA2 complex. To understand the role played by BRCA2 in this
      complex, we deleted its N-terminal segment and generated BRCA2(Delta)(N) mutant
      cells. Although previous studies have suggested that BRCA1-PALB2 plays a role in
      the recruitment of BRCA2 to DNA-damage sites, BRCA2(Delta)(N) mutant cells
      displayed a considerably milder phenotype than did BRCA2(-/-) null-deficient
      cells. We hypothesized that the DNA-binding domain (DBD) of BRCA2 might
      compensate for a defect in BRCA2(DeltaN) that prevented stable interaction with
      PALB2. To test this hypothesis, we disrupted the DBD of BRCA2 in wild-type and
      BRCA2(Delta)(N) cells. Remarkably, although the resulting BRCA2(Delta)(DBD) cells
      displayed a moderate phenotype, the BRCA2(Delta)(N+DeltaDBD) cells displayed a
      very severe phenotype, as did the BRCA2(-/-) cells, suggesting that the N
      terminal segment and the DBD play a substantially overlapping role in the
      functionality of BRCA2. We also showed that the formation of both the BRCA1-PALB2
      BRCA2 complex and the DBD is required for efficient recruitment of BRCA2 to DNA
      damage sites. Our study revealed the essential role played by both the BRCA1
      PALB2-BRCA2 complex and the DBD in the functionality of BRCA2, as each can
      compensate for the other in the recruitment of BRCA2 to DNA-damage sites. This
      knowledge adds to our ability to accurately predict the efficacy of antimalignant
      therapies for patients carrying mutations in the BRCA2 gene.

PMID- 24285742
TI  - Ab initio studies on the proton dissociation and infrared spectra of sulfonated
      poly(ether ether ketone) (SPEEK) membranes.
AB  - SPEEK is known to possess high proton conductivity at high water content, being
      comparable with other popular membranes used in fuel cells, such as Nafion and
      sulfonated polyethersulfone (SPES). However, much less is known about its
      fundamental properties, including the status of proton dissociation and spectral
      features. In this work, the properties of two model molecules of SPEEK, M1 (20
      atoms), M2 (50 atoms) and their hydrated systems, M1 + nH2O and M2 + nH2O (n = 1
      9), have been investigated using static electronic structure calculations and the
      ab initio molecular dynamics (MD) method. Optimized structures for all of the
      systems and the trajectories of M1 + nH2O (n = 3-6) at finite temperatures have
      been computed using density functional theory at the B3LYP level of theory.
      Proton dissociation has been discussed in detail, especially for n = 3 and n = 4.
      In addition, the infrared spectra of SPEEK and its hydrated systems have been
      studied using a combination of theory and experiment. The characteristic bands of
      SPEEK and the surrounding water clusters have been assigned with emphasis on
      their relationship with the degree of proton dissociation. We have found that the
      hydronium ion stretching modes, which appear in the 2000-3000 cm(-1) region in
      static electronic structure calculations, are not observed experimentally. This
      discrepancy is explained by the stationary structure and the temperature effect. 

PMID- 24285728
TI  - Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and
      glutathione synthesis.
AB  - Myc oncoproteins induce genes driving aerobic glycolysis, including lactate
      dehydrogenase-A that generates lactate. Here, we report that Myc controls
      transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1
      levels are manifest in premalignant and neoplastic EMU-Myc transgenic B cells and
      in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1
      function leads to an accumulation of intracellular lactate that rapidly disables
      tumor cell growth and glycolysis, provoking marked alterations in glycolytic
      intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and
      ultimately, glutathione (GSH). Reductions in GSH then lead to increases in
      hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally,
      forcing glycolysis by metformin treatment augments this response and the efficacy
      of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1
      expressing malignancies.

PMID- 24285743
TI  - Plasma protein biomarkers of the geriatric syndrome of frailty.
AB  - Frailty is a geriatric syndrome associated with physical decline with aging.
      Using a proteomics-based screening method to screen plasma for potential
      biomarkers, we previously found inflammatory glycoproteins to be increased with
      frailty. The purpose of this study was to confirm if plasma levels of these
      glycoproteins, as well as of interleukin-6, are increased with frailty in a
      larger sample (n = 65) of community-dwelling older adults. Plasma levels of
      transferrin, fibrinogen, haptoglobin, and interleukin-6 were determined with
      enzyme-linked immunosorbent assay. Differences in protein concentrations by
      frailty status were determined using analysis of variance. Higher levels of
      transferrin (p < .001), fibrinogen (p < .0001), and interleukin-6 (p = .0035)
      were associated with frailty status (nonfrail, prefrail, or frail) and frailty
      score (0-5) in this sample even after adjustment for age and sex. Haptoglobin did
      not differ by frailty status (p = .05). Our findings largely confirmed the
      findings of our nontargeted approach that inflammatory glycoproteins are
      increased with frailty. Future studies should include larger examinations of
      these associations and consider the potential usefulness of these glycoproteins
      as biomarkers for frailty. 

PMID- 24285745
TI  - Associations of childhood socioeconomic status and adulthood height with
      functional limitations among Japanese older people: results from the JAGES 2010
      Project.
AB  - BACKGROUND: We examined the associations between childhood socioeconomic status
      and adulthood height with functional limitations in old age. METHODS: Data were
      obtained from the baseline survey of the Japan Gerontological Evaluation Study
      2010, a population-based cohort of people aged >=65 years enrolled from 27
      municipalities across Japan (N = 15,499). People aged 65-69, 70-74, 75-79, and
      >=80 years experienced the end of World War II when they were aged 0-4, 5-9, 10
      14, and >=15 years, respectively. Subjective socioeconomic status during
      childhood and current height were obtained by self-report through questionnaire
      in 2010. Higher-level functional capacity was assessed using a validated
      questionnaire scale. Poisson regression with robust variance estimator was
      employed to determine the association between childhood subjective socioeconomic
      status, height, and functional limitations. RESULTS: Lower childhood subjective
      socioeconomic status was consistently associated with higher prevalence rate
      ratio of limitations in higher-level functional capacity, regardless of age
      cohort. Height was associated with functional limitation only among the group
      aged 70-74 years: taller (>=170cm for men and >=160cm for women) people were 16%
      less likely to report functional limitation in comparison with shorter (<155 cm
      for men and <145 cm for women) individuals in the fully adjusted model
      (prevalence rate ratio: 0.84, 95% confidence interval: 0.74-0.96). CONCLUSIONS:
      Low childhood subjective socioeconomic status had a robust association with
      functional limitation regardless of age cohort. In addition, those who lived
      through World War II before they reached puberty and attained shorter height were
      more likely to report functional limitations in old age.

PMID- 24285744
TI  - Intraindividual variability in executive functions but not speed of processing or
      conflict resolution predicts performance differences in gait speed in older
      adults.
AB  - BACKGROUND: The relationship between executive functions (EF) and gait speed is
      well established. However, with the exception of dual tasking, the key components
      of EF that predict differences in gait performance have not been determined.
      Therefore, the current study was designed to determine whether processing speed,
      conflict resolution, and intraindividual variability in EF predicted variance in
      gait performance in single- and dual-task conditions. METHODS: Participants were
      234 nondemented older adults (mean age 76.48 years; 55% women) enrolled in a
      community-based cohort study. Gait speed was assessed using an instrumented
      walkway during single- and dual-task conditions. The flanker task was used to
      assess EF. RESULTS: Results from the linear mixed effects model showed that (a)
      dual-task interference caused a significant dual-task cost in gait speed
      (estimate = 35.99; 95% CI = 33.19-38.80) and (b) of the cognitive predictors,
      only intraindividual variability was associated with gait speed (estimate = 
      .606; 95% CI = -1.11 to -.10). In unadjusted analyses, the three EF measures were
      related to gait speed in single- and dual-task conditions. However, in fully
      adjusted linear regression analysis, only intraindividual variability predicted
      performance differences in gait speed during dual tasking (B = -.901; 95% CI = 
      1.557 to -.245). CONCLUSION: Among the three EF measures assessed,
      intraindividual variability but not speed of processing or conflict resolution
      predicted performance differences in gait speed.

PMID- 24285746
TI  - Obesity in the sarcopenia era.

PMID- 24285747
TI  - Growth hormone alters the glutathione S-transferase and mitochondrial thioredoxin
      systems in long-living Ames dwarf mice.
AB  - Ames dwarf mice are deficient in growth hormone (GH), prolactin, and thyroid
      stimulating hormone and live significantly longer than their wild-type (WT)
      siblings. The lack of GH is associated with stress resistance and increased
      longevity. However, the mechanism underlying GH's actions on cellular stress
      defense have yet to be elucidated. In this study, WT or Ames dwarf mice were
      treated with saline or GH (WT saline, Dwarf saline, and Dwarf GH) two times daily
      for 7 days. The body and liver weights of Ames dwarf mice were significantly
      increased after 7 days of GH administration. Mitochondrial protein levels of the
      glutathione S-transferase (GST) isozymes, K1 and M4 (GSTK1 and GSTM4), were
      significantly higher in dwarf mice (Dwarf saline) when compared with WT mice (WT
      saline). GH administration downregulated the expression of GSTK1 proteins in
      dwarf mice. We further investigated GST activity from liver lysates using
      different substrates. Substrate-specific GST activity (bromosulfophthalein,
      dichloronitrobenzene, and 4-hydrox-ynonenal) was significantly reduced in GH
      treated dwarf mice. In addition, GH treatment attenuated the activity of
      thioredoxin and glutaredoxin in liver mitochondria of Ames mice. Importantly, GH
      treatment suppressed Trx2 and TrxR2 mRNA expression. These data indicate that GH
      has a role in stress resistance by altering the functional capacity of the GST
      system through the regulation of specific GST family members in long-living Ames
      dwarf mice. It also affects the regulation of thioredoxin and glutaredoxin,
      factors that regulate posttranslational modification of proteins and redox
      balance, thereby further influencing stress resistance. 

PMID- 24285748
TI  - Toll-interacting protein (Tollip) negatively regulates pressure overload-induced
      ventricular hypertrophy in mice.
AB  - AIMS: Toll-interacting protein (Tollip) is a critical regulator of the Toll-like
      receptor-mediated signalling pathway. However, the role of Tollip in chronic
      pressure overload-induced cardiac hypertrophy remains unclear. This study aimed
      to determine the functional significance of Tollip in the regulation of aortic
      banding-induced cardiac remodelling and its underlying mechanisms. METHODS AND
      RESULTS: First, we observed that Tollip was down-regulated in human failing
      hearts and murine hypertrophic hearts, as determined by western blotting and RT
      PCR. Using cultured neonatal rat cardiomyocytes, we found that adenovirus vector
      mediated overexpression of Tollip limited angiotensin II-induced cell
      hypertrophy; whereas knockdown of Tollip by shRNA exhibited the opposite effects.
      We then generated a transgenic (TG) mouse model with cardiac specific
      overexpression of Tollip and subjected them to aortic banding (AB) for 8 weeks.
      When compared with AB-treated wild-type mouse hearts, Tollip-TGs showed a
      significant attenuation of cardiac hypertrophy, fibrosis, and dysfunction, as
      measured by echocardiography, immune-staining, and molecular/biochemical
      analysis. Conversely, a global Tollip-knockout mouse model revealed an aggravated
      cardiac hypertrophy and accelerated maladaptation to chronic pressure
      overloading. Mechanistically, we discovered that Tollip interacted with AKT and
      suppressed its downstream signalling pathway. Pre-activation of AKT in
      cardiomyocytes largely offset the Tollip-elicited anti-hypertrophic effects.
      CONCLUSION: Our results provide the first evidence that Tollip serves as a
      negative regulator of pathological cardiac hypertrophy by blocking the AKT
      signalling pathway.

PMID- 24285749
TI  - Laser microdissection coupled to transcriptional profiling of Arabidopsis roots
      inoculated by Plasmodiophora brassicae indicates a role for brassinosteroids in
      clubroot formation.
AB  - The clubroot disease caused by the obligate biotrophic protist Plasmodiophora
      brassicae on host plants of the Brassicaceae family is characterized by enhanced
      cell division and cell expansion. Since a typical root section of an infected
      plant always includes different stages of the pathogen as well as uninfected
      cells, we were interested in investigating specific developmental stages of the
      pathogen and their effect on host transcriptional changes. We extended previous
      microarray studies on whole roots by using laser microdissection and pressure
      catapulting (LMPC) to isolate individual cells harboring defined developmental
      stages of the pathogen. In addition, we compared the central cylinder of infected
      plants with that of control plants. We were especially interested in elucidating
      the stage-specific hormonal network. The up-regulation of genes involved in auxin
      and cytokinin metabolism and signaling was confirmed. In addition, we found
      evidence that brassinosteroid (BR) synthesis and signal perception genes were in
      many cases up-regulated in enlarged cells and the central cylinder. This was
      confirmed by quantitative PCR. Treatment of wild-type plants with the BR
      biosynthesis inhibitor propiconazole reduced gall formation, and the analysis of
      the BR receptor mutant bri1-6 revealed less severe gall formation than in the
      respective wild type. Our results identify novel hormone pathways involved in
      clubroot development. Using LMPC to generate pools of homogeneous cell type
      populations combined with transcriptome analysis has been very useful to
      elucidate the regulation of gall growth by this obligate biotropic pathogen in a
      cell- and stage-specific manner. 

PMID- 24285750
TI  - The Arabidopsis tandem zinc finger 9 protein binds RNA and mediates pathogen
      associated molecular pattern-triggered immune responses.
AB  - Recognition of pathogen-associated molecular patterns (PAMPs) induces multiple
      defense mechanisms to limit pathogen growth. Here, we show that the Arabidopsis
      thaliana tandem zinc finger protein 9 (TZF9) is phosphorylated by PAMP-responsive
      mitogen-activated protein kinases (MAPKs) and is required to trigger a full PAMP
      triggered immune response. Analysis of a tzf9 mutant revealed attenuation in
      specific PAMP-triggered reactions such as reactive oxygen species accumulation,
      MAPK activation and, partially, the expression of several PAMP-responsive genes.
      In accordance with these weaker PAMP-triggered responses, tzf9 mutant plants
      exhibit enhanced susceptibility to virulent Pseudomonas syringae pv. tomato
      DC3000. Visualization of TZF9 localization by fusion to green fluorescent protein
      revealed cytoplasmic foci that co-localize with marker proteins of processing
      bodies (P-bodies). This localization pattern is affected by inhibitor treatments
      that limit mRNA availability (such as cycloheximide or actinomycin D) or block
      nuclear export (leptomycin B). Coupled with its ability to bind the
      ribohomopolymers poly(rU) and poly(rG), these results suggest involvement of TZF9
      in post-transcriptional regulation, such as mRNA processing or storage pathways,
      to regulate plant innate immunity. 

PMID- 24285751
TI  - KNApSAcK Metabolite Activity Database for retrieving the relationships between
      metabolites and biological activities.
AB  - Databases (DBs) are required by various omics fields because the volume of
      molecular biology data is increasing rapidly. In this study, we provide
      instructions for users and describe the current status of our metabolite activity
      DB. To facilitate a comprehensive understanding of the interactions between the
      metabolites of organisms and the chemical-level contribution of metabolites to
      human health, we constructed a metabolite activity DB known as the KNApSAcK
      Metabolite Activity DB. It comprises 9,584 triplet relationships (metabolite
      biological activity-target species), including 2,356 metabolites, 140 activity
      categories, 2,963 specific descriptions of biological activities and 778 target
      species. Approximately 46% of the activities described in the DB are related to
      chemical ecology, most of which are attributed to antimicrobial agents and plant
      growth regulators. The majority of the metabolites with antimicrobial activities
      are flavonoids and phenylpropanoids. The metabolites with plant growth regulatory
      effects include plant hormones. Over half of the DB contents are related to human
      health care and medicine. The five largest groups are toxins, anticancer agents,
      nervous system agents, cardiovascular agents and non-therapeutic agents, such as
      flavors and fragrances. The KNApSAcK Metabolite Activity DB is integrated within
      the KNApSAcK Family DBs to facilitate further systematized research in various
      omics fields, especially metabolomics, nutrigenomics and foodomics. The KNApSAcK
      Metabolite Activity DB could also be utilized for developing novel drugs and
      materials, as well as for identifying viable drug resources and other useful
      compounds. 

PMID- 24285752
TI  - Carotenoid analysis of a liverwort Marchantia polymorpha and functional
      identification of its lycopene beta- and epsilon-cyclase genes.
AB  - Carotenoid biosynthesis in bryophytes has yet to be clarified. The liverwort
      Marchantia polymorpha L. is known to be an early land plant and is an emerging
      bryophyte model. In order to gain insight into the evolution of carotenoid
      biosynthesis in plants, we studied carotenoid biosynthesis in this liverwort. As
      is the case in higher plants, liverwort thalli contain lutein and beta-carotene,
      as major carotenoids, as well as zeaxanthin, antheraxanthin, violaxanthin and 9'
      cis-neoxanthin. Based on liverwort expressed sequence tag (EST)/cDNA and genome
      sequences, we isolated two cyclase genes encoding lycopene beta-cyclase (LCYb)
      and lycopene epsilon-cyclase (LCYe), which were involved in the synthesis of beta
      carotene and alpha-carotene. These enzymes were phylogenetically positioned
      between corresponding proteins of a green alga (Chlorophyta) and higher plants.
      Functional analysis of the two genes was performed using a heterologous
      Escherichia coli expression system, in which the Pantoea ananatis lycopene
      biosynthesis genes were co-expressed. The results indicated liverwort LCYb
      activity for the synthesis of beta-carotene from lycopene, which was the same as
      that of higher plants. On the other hand, liverwort LCYe was able to form two
      epsilon-rings from lycopene to epsilon-carotene via delta-carotene, which was
      different from the Arabidopsis LCYe enzyme which generates only one epsilon-ring
      from lycopene. 

PMID- 24285753
TI  - Knockdown of LjIPT3 influences nodule development in Lotus japonicus.
AB  - Cytokinins play important roles in legume-rhizobia symbiosis. Here we report
      isolation of six genes encoding isopentenyl transferase (IPT) from Lotus
      japonicus, which catalyze the rate-limiting step of cytokinin biosynthesis. The
      LjIPT3 gene was found to be up-regulated in infected roots and mature nodules.
      Histochemical analysis demonstrated expression of Pro(LjIPT3):GUS (beta
      glucuronidase) in vegetative and reproductive organs, and was especially high in
      the vascular bundles of roots. When inoculated with Mesorhizobium loti
      MAFF303099, LjIPT3 was undetectable in the nodule primordia and developing
      nodules, and later it was expressed only in the vascular bundles of mature
      nodules. In addition, knockdown of LjIPT3 (LjIPT3i) by RNA interference reduced
      levels of endogenous cytokinins, affected plant development and accelerated Chl
      degradation during dark-induced leaf senescence. Compared with the wild type,
      LjIPT3i plants produced fewer infection threads and nodules. In addition,
      expression of downstream nodulation-related transcription factor genes LjNSP1,
      LjNSP2 and LjNIN decreased dramatically in LjIPT3i plants. These results suggest
      that LjIPT3 regulates the CRE1-dependent cytokinin pathway, affecting nodule
      initiation and thereby influencing the number of infection threads and nodules.
      Detection of nitrogenase activity and observation of nodule structure showed that
      endogenous cytokinins are required for full development of the infected cells in
      mature nodules by preventing early senescence. Therefore, our results indicate
      that the LjIPT3 gene product is required for nodule initiation and development,
      and does not appear to be involved in early infection events.

PMID- 24285755
TI  - The transcriptional regulatory mechanism of the peroxisomal ascorbate peroxidase
      (pAPX) gene cloned from an extreme halophyte, Salicornia brachiata.
AB  - Peroxisomal ascorbate peroxidase detoxifies H2O2 leaching out from peroxisomes
      into the cytoplasm. The present study describes transcript expression and cis
      regulation of the SbpAPX gene cloned from an extreme halophyte, Salicornia
      brachiata, in the steady state and under different stresses. About 2-fold
      elevated transcript expression was found in salt- and drought-treated shoots at
      12 h compared with control, while 1.9-fold increased expression was observed
      under heat treatment. In roots, the transcript level was down-regulated at 2 h,
      thereafter increasing with the time of exposure and reaching a maximum at the
      control level. The SbpAPX promoter has characteristic cis-regulatory ABA
      dependent abiotic stress-responsive elements. The full-length promoter (1,024 bp,
      PP1) and deletion constructs -838 (PP2), -697 (PP3), -433 (PP4) and -185 bp (PP5)
      were fused with the GUS (beta-glucuronidase) gene and transformed into tobacco
      for functional validation. Expression of GUS increased significantly in
      transgenic plants under stress. Quantitative expression analysis of GUS in T1
      plants revealed that promoter PP5 is efficient for gene expression. In planta
      transient expression further suggested that the promoter PP5 contains efficient
      stress-inducible elements. A steep decline in GUS expression in PP3, and
      thereafter an elevated expression in PP4 and PP5, suggested the presence of a
      repressor element between -696 and -433 bp, while an enhancer element was
      predicted between -838 and -697 bp. Further, transient expression analyses and
      electrophoretic mobility shift assay revealed that the core sequence of cis
      acting motifs ATAA and CCTCAA function as enhancer and repressor binding sites,
      respectively. Based on the study, a model is proposed for the cis-regulation of
      the SbpAPX gene. The present study provides a useful insight for understanding
      gene expression regulation in a halophyte with or without stress. Furthermore,
      potential stress-responsive promoter-driven expression of introgressed gene(s)
      can be used for engineering crops with enhanced stress tolerance.

PMID- 24285754
TI  - UGT74D1 catalyzes the glucosylation of 2-oxindole-3-acetic acid in the auxin
      metabolic pathway in Arabidopsis.
AB  - IAA is a naturally occurring auxin that plays a crucial role in the regulation of
      plant growth and development. The endogenous concentration of IAA is
      spatiotemporally regulated by biosynthesis, transport and its inactivation in
      plants. Previous studies have shown that the metabolism of IAA to 2-oxindole-3
      acetic acid (OxIAA) and OxIAA-glucoside (OxIAA-Glc) may play an important role in
      IAA homeostasis, but the genes involved in this metabolic pathway are still
      unknown. In this study, we show that UGT74D1 catalyzes the glucosylation of OxIAA
      in Arabidopsis. By screening yeasts transformed with Arabidopsis UDP
      glycosyltransferase (UGT) genes, we found that OxIAA-Glc accumulates in the
      culture media of yeasts expressing UGT74D1 in the presence of OxIAA. Further, we
      showed that UGT74D1 expressed in Escherichia coli converts OxIAA to OxIAA-Glc.
      The endogenous concentration of OxIAA-Glc decreased by 85% while that of OxIAA
      increased 2.5-fold in ugt74d1-deficient mutants, indicating the major role of
      UGT74D1 in OxIAA metabolism. Moreover, the induction of UGT74D1 markedly
      increased the level of OxIAA-Glc and loss of root gravitropism. These results
      indicate that UGT74D1 catalyzes a committed step in the OxIAA-dependent IAA
      metabolic pathway in Arabidopsis. 

PMID- 24285756
TI  - Implementation of a dexmedetomidine stewardship program at a tertiary academic
      medical center.
AB  - BACKGROUND: Brigham and Women's Hospital implemented a dexmedetomidine
      stewardship program in October 2010 beginning with an institution-specific
      prescribing guideline. To ensure continued adherence to the prescribing
      guideline, a pharmacist-driven quality assurance program was implemented in
      November 2011. OBJECTIVE: The primary objective of this study is to describe the
      role and impact of a dexmedetomidine stewardship program on dexmedetomidine use
      at a tertiary academic medical center. METHODS: This is a prospective descriptive
      analysis of a dexmedetomidine stewardship program. Dexmedetomidine stewardship
      data were collected prospectively from January 2012 through June 2012, in all
      intensive care units (ICUs) at a single academic medical center. Adult patients
      (>18 years old) receiving dexmedetomidine therapy continuously for sedation and
      in the ICU were included in the analysis. RESULTS: A total of 99 patients were
      identified during the study time frame, during which 71 (71.7%) were identified
      as compliant with the institutional guideline. The total number of patients
      receiving dexmedetomidine for greater than 24 hours was 13 (13.1%), of whom 10
      (76.9%) received targeted interventions; 15 (15.2%) targeted interventions were
      made on all patients receiving dexmedetomidine during the study time frame. The
      total use of dexmedetomidine during the study period was 1310 vials, compared
      with 5404 vials during the equivalent time frame in 2010-a 76% reduction.
      CONCLUSIONS: A dexmedetomidine stewardship program, including an institution
      specific prescribing guideline and a pharmacist-driven quality assurance program
      may ensure guideline compliance and decreased use of dexmedetomidine at an
      academic medical center.

PMID- 24285757
TI  - Efficacy of alvimopan following bowel resection: a comparison of two dosing
      strategies.
AB  - BACKGROUND: Alvimopan is indicated to accelerate the time to gastrointestinal
      recovery following partial bowel resection with primary anastomosis. The approved
      dosing regimen includes an initial dose prior to surgery and 12 mg twice daily
      after surgery for up to 7 days; however, there are no human studies evaluating
      the need for the preoperative dose. We report our experience with
      gastrointestinal recovery when the preoperative dose is omitted. OBJECTIVE: To
      evaluate the efficacy of alvimopan therapy when the preoperative dose is not
      administered. METHODS: This retrospective study included elective surgery
      patients who underwent bowel resection with primary anastomosis without colostomy
      or ileostomy. The study compared (a) patients who received alvimopan and received
      a dose preoperatively, (b) patients who received alvimopan but did not receive a
      dose preoperatively, and (c) matched control patients who did not receive
      alvimopan. Length of stay following bowel resection, direct hospital costs, time
      to first bowel movement, and time to oral diet were evaluated. RESULTS: Of 50
      patients who received alvimopan, 27 received the preoperative dose and 23 did
      not. These 50 patients were matched to similar control patients who received no
      alvimopan during their admission for resection. Compared with controls, time to
      discharge was significantly shorter in patients who received alvimopan,
      regardless of whether the preoperative dose was administered (P < .001) or
      omitted (P = .03). Patients who did not receive the preoperative dose still
      experienced faster time to first bowel movement (71 vs 97 hours; P = .006) and
      faster time to first diet (17 vs 54 hours; P < .001) than non-alvimopan users.
      CONCLUSION: Patients receiving the approved alvimopan dosing regimen experienced
      the most rapid recovery of gastrointestinal function. However, administering
      alvimopan only postoperatively (if the preoperative dose is omitted) may still
      reduce the severity of postoperative ileus.

PMID- 24285758
TI  - Performance of the adverse drug event trigger tool and the global trigger tool
      for identifying adverse drug events: experience in a Belgian hospital.
AB  - BACKGROUND: Medication-related harm can be detected using the adverse drug event
      (ADE) trigger tool and the medication module of the Global Trigger Tool (GTT)
      developed by the Institute for Healthcare Improvement (IHI). In recent years,
      there has been some controversy on the performance of this method. In addition,
      there are limited data on the performance of the medication module of the GTT as
      compared with the ADE trigger tool. OBJECTIVES: To evaluate the performance of
      the ADE trigger tool and of the medication module of the GTT for identifying
      ADEs. METHODS: The methodology of the IHI was used. A random sample of 20 adult
      admissions per month was selected over a 12-month period in a teaching hospital
      in Belgium. The ADE trigger tool was adapted to the Belgian setting and included
      20 triggers. The positive predictive value (PPV) of each trigger was calculated,
      as well as the proportion of ADEs that would have been identified with the
      medication module of the GTT as compared with the ADE trigger tool. RESULTS: A
      total of 200 triggers and 62 ADEs were found, representing 26 ADEs/100
      admissions. Nineteen ADEs (31%) were found spontaneously without the presence of
      a trigger. Three triggers never occurred. The PPVs of other triggers varied from
      0 to 0.67, with half of them having PPVs less than 0.20. If we had used the
      medication triggers included in the GTT (n = 11), we would have identified 77% of
      total ADEs and 67% of preventable ADEs. CONCLUSIONS: Applying the trigger tool
      method proposed by the IHI to a Belgian hospital led to the identification of one
      ADE out of 4 admissions. To increase performance, refining the list of triggers
      in the ADE trigger tool and in the medication module of the GTT would be needed.
      Recording nontriggered events should be encouraged.

PMID- 24285759
TI  - Bleeding events following concurrent use of warfarin and oseltamivir by Medicare
      beneficiaries.
AB  - BACKGROUND: During the 2009 H1N1 influenza pandemic, the UK Medicines and
      Healthcare Products Regulatory Agency received case reports suggesting a
      potentiation of warfarin anticoagulation by the antiviral drug oseltamivir. We
      evaluated this putative interaction using Medicare data. OBJECTIVE: To determine
      the frequency of bleeding following addition of oseltamivir or comparator drugs
      among Medicare beneficiaries taking warfarin. METHODS: This was a retrospective
      cohort evaluation using Medicare nationwide data. Cohort members were Medicare
      Parts A, B, and D beneficiaries from June 30, 2006 to October 31, 2010 receiving
      warfarin for at least 1 month prior to a concomitant drug of interest
      (oseltamivir, ampicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and
      angiotensin-converting enzyme (ACE) inhibitors). Bleeding within 14 days of new
      prescriptions for oseltamivir or comparators was identified using inpatient or
      emergency department ICD-9 (International Classification of Diseases, ninth
      revision) discharge diagnosis codes for gastrointestinal hemorrhage, epistaxis,
      hematuria, and intracranial bleeding. Patients with bleeding within 30 days
      preceding the prescription concomitant to warfarin were excluded. RESULTS: With
      concomitant ACE inhibitors as reference, adjusted odds ratios (ORs) for any
      bleeding events within 14 days were 1.47 (95% confidence interval [CI] = 1.08
      1.88), 1.24 (95% CI = 0.97-1.57), and 2.74 (95% CI = 2.53-3.03), for warfarin
      plus ampicillin, oseltamivir, and TMP-SMX, respectively. In a sensitivity
      analysis, adjusted ORs over a 7-day period were 1.89 (95% CI = 1.29-2.59), 1.47
      (95% CI = 1.06-2.02), and 3.07 (95% CI = 2.76-3.49) for warfarin plus ampicillin,
      oseltamivir, and TMP-SMX, respectively. CONCLUSIONS: Bleeding with oseltamivir
      plus warfarin was not significantly increased over a 14-day observation period; a
      sensitivity analysis showed a statistically significant increase over a 7-day
      period; in contrast, the data consistently showed the known tendency of TMP-SMX
      to potentiate the effects of warfarin. The results should be interpreted with the
      limitations of this approach in mind, including the inability to control for
      unmeasured confounders.

PMID- 24285760
TI  - Association of age with polypharmacy and risk of drug interactions with
      antiretroviral medications in HIV-positive patients.
AB  - BACKGROUND: Interactions between antiretroviral (ARV) therapy and medications to
      treat age-related comorbidities are a growing concern in the aging HIV
      population. OBJECTIVE: To investigate the association of age with potential drug
      drug interactions (PDDIs) involving ARVs. METHODS: We studied ARV-treated
      patients attending a tertiary care center. PDDIs were classified as "red flag"
      (contraindicated) or "orange flag" (use with caution or dose adjustment).
      Logistic regression was used to determine the association of age with the
      occurrence of >=1 PDDI. RESULTS: Of 914 patients (78% male, median age 49 years),
      older patients (age >=50 years) were on more drugs than younger patients (total 9
      vs 7; P < .0001) and were more likely to be on ritonavir-boosted protease
      inhibitors (PIs), integrase inhibitors, and non-ARV medications. Older patients
      were more likely to have >=1 orange flag PDDI (71% vs 55%, P < .0001) and to have
      a red flag PDDI (5% vs 2%, P = .07), although the latter did not reach
      statistical significance. A 10-year increase in age was associated with an
      increased likelihood of >=1 PDDI (odds ratio [OR] = 1.72; P < .0001) after
      adjusting for gender, race and number and class of ARVs. The effect of age was
      diminished after adjusting further for the number of non-ARV medications (OR =
      1.28; P = .02) and use of cardiovascular drugs (OR = 1.16; P = .21). CONCLUSIONS:
      In our clinic population, older patients were more likely to have a PDDI because
      of the greater number of non-ARV medications, particularly cardiovascular agents.

PMID- 24285761
TI  - Feasibility of a pharmacy-based influenza immunization program in an academic
      emergency department.
AB  - BACKGROUND: From September 2002 to August 2010, 13 patients who were discharged
      from the emergency department (ED) were immunized against influenza. This
      correlates with a time when pharmacists were not permitted to vaccinate patients
      in New York. OBJECTIVE: The objectives of this study were to determine the
      feasibility of a pharmacist-based influenza vaccination program in the ED, assess
      patients' willingness to be vaccinated by a pharmacist, and identify reasons for
      declination. METHODS: This was a cross-sectional study involving English-speaking
      patients older than 18 years. The pharmacist vaccinated patients, if they
      consented. Patients who refused to be vaccinated were asked why they did not want
      to receive the vaccine and their perception of pharmacists vaccinating patients
      in the ED. The percentage of patients vaccinated; time elements associated with
      the process of screening, counseling, and vaccinating; and the type and frequency
      of adverse events were recorded. RESULTS: Of 149 patients, 62 patients (41%)
      agreed to receive the vaccine, a 4-fold increase from the previous 8 years. The
      median screening and vaccination time was 8 minutes. Of those not receiving a
      vaccine in the ED, 74% were willing to receive the influenza vaccine from a
      pharmacist, and 78% were willing to receive the vaccine in the ED. The most
      common reason for refusal was perception of low self-risk (43.9%). No adverse
      events were reported. CONCLUSIONS: A pharmacist-based influenza immunization
      program is feasible in the ED and has the potential to successfully and safely
      increase the percentage of adult patients receiving the vaccine.

PMID- 24285762
TI  - An observational study of ezetimibe in cardiac transplant recipients receiving
      calcineurin inhibitors.
AB  - BACKGROUND: Cardiac transplant patients are at risk for developing cardiac
      allograft vasculopathy, and dyslipidemia in this patient population has been
      associated with increased risk. Data evaluating the efficacy and safety of
      ezetimibe in this population are minimal. OBJECTIVES: The purpose of this study
      was to assess the effects of ezetimibe, alone or in combination with other lipid
      lowering agents, in cardiac transplant recipients receiving calcineurin
      inhibitors (CNIs). METHODS: This study was a single-center retrospective chart
      review. Data on demographics, medications prescribed for dyslipidemia and
      prevention of transplant rejection, results of lipid panels, CNI blood
      concentrations, and adverse effects were extracted from medical records of
      cardiac transplant recipients who were prescribed ezetimibe, either alone or in
      combination with other lipid-lowering agents, and seen at least once in a 12
      month period at a cardiac transplantation clinic of an 800-bed teaching hospital.
      RESULTS: There were 71 patients prescribed ezetimibe in whom a safety analysis
      was performed. Approximately 49% (n = 35) were included in the analysis for lipid
      lowering. Ezetimibe significantly decreased low-density lipoprotein cholesterol
      (LDL-C; 129 mg/dL vs 94 mg/dL, P < .0001), non-high-density lipoprotein
      cholesterol (non-HDL-C; 170 mg/dL vs 127.5 mg/dL, P = .0058), and total
      cholesterol (236 mg/dL vs 200 mg/dL, P < .0001). There was no significant change
      in HDL-C and triglycerides as compared with baseline. The proportion of patients
      achieving goal LDL-C < 100 mg/dL significantly increased from 11.5% at baseline
      to 60.5% after the addition of ezetimibe (P < .0001). Ezetimibe had no measurable
      effect on blood CNI concentrations or doses. Adverse effects were reported by
      15.5% of patients (n = 11), with 4% (n = 3) of patients discontinuing therapy.
      The most common complaints were gastrointestinal intolerance and myalgia.
      CONCLUSIONS: Ezetimibe was associated with lower LDL-C in cardiac transplant
      recipients either as combination therapy in patients with elevated LDL-C or as
      monotherapy, with a low frequency of adverse effects.

PMID- 24285763
TI  - Pharmacist-physician collaboration for diabetes care: cardiovascular outcomes.
AB  - BACKGROUND: Only 23% of patients are meeting all goals for cardiovascular
      complications of diabetes. OBJECTIVE: The purpose of our study is to evaluate the
      effect of a pharmacist-physician collaboration on attainment of cardiovascular
      related goals in patients with type 2 diabetes. METHODS: This prospective,
      multicenter cohort enrolled patients from 7 practice sites that were members of
      the University of Tennessee Pharmacist Practice Based Research Network (UT Pharm
      Net). Patients were included if they were diagnosed with type 2 diabetes, at
      least 18 years of age and English speaking. Pregnant patients were excluded.
      Patients were followed for 12 months after enrollment. Primary cardiovascular
      outcomes included reduction in systolic blood pressure, diastolic blood pressure,
      and low-density lipoprotein (LDL) as well as the proportion of patients achieving
      a blood pressure goal of <130/80 mm Hg and proportion of patients achieving an
      LDL goal of <100 mg/dL. RESULTS: For the 206 patients enrolled, the average age
      was 59.7 years; the majority were male (59.7%) and white (66%). When compared
      with baseline, the postintervention mean systolic (P < .0001), diastolic blood
      pressure (P = .0003), and LDL (P < .0001) decreased significantly. The proportion
      of patients achieving a blood pressure of <130/80 mm Hg increased 21.8% (P <
      .0001), and the proportion of patients achieving an LDL of <100 mg/dL increased
      12% (P = .0023). CONCLUSIONS: The results of our study indicate that
      collaborative management has a positive impact on decreasing cardiovascular risk
      and assists patients in attaining national goals for blood pressure and
      cholesterol.

PMID- 24285764
TI  - Tofacitinib: The First Janus Kinase (JAK) inhibitor for the treatment of
      rheumatoid arthritis.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy and safety,
      dosage administration, and adverse effects of tofacitinib for rheumatoid
      arthritis (RA) treatment. DATA SOURCES: Primary sources of information were
      obtained from clinical studies, which were identified through PubMed (1966 to
      June 2013) and International Pharmaceutical Abstracts (1970 to March 2013) using
      terms: tofacitinib, tasocitinib, CP-690550, and CP-690,550. Information was used
      from tofacitinib package insert, guidelines, and published abstracts from the
      American College of Rheumatology (ACR) and the European League Against
      Rheumatism. STUDY SELECTION AND DATA EXTRACTION: Data search was limited to
      include publications in English language and from human subjects. DATA SYNTHESIS:
      Tofacitinib is the first oral Janus kinase inhibitor indicated for treatment of
      moderate to severe RA. Tofacitinib demonstrated efficacy and safety comparable to
      other disease-modifying antirheumatic drugs (DMARDs). Tofacitinib was efficacious
      in RA patients, indicated by achievements of ACR20, ACR50, and ACR70 criteria.
      Similar improvements were observed in patients who met remission criteria based
      on the Disease Activity Scores 28 criteria and quality of life as measured by the
      Health Assessment Questionnaire-Disability Index (HAQ-DI). Tofacitinib was
      associated with infections and malignancies; and elevations in serum creatinine
      and lipids were observed. Drug interactions with inducers and inhibitors of the
      cytochrome P-450 3A4 and 2C9 isoenzymes were reported. CONCLUSIONS: Tofacitinib
      is an oral treatment option for RA patients who have inadequate response or
      intolerance to methotrexate. Postmarket surveillance will provide further insight
      to tofacitinib's role in RA therapy, especially in patients who may require
      different types of combination therapy with DMARDS.

PMID- 24285765
TI  - Alogliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of
      alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in the management of type
      2 diabetes mellitus (T2DM). DATA SOURCES: Searches were conducted in MEDLINE
      (1946-August 2013) and Embase (1974-August 2013) for English language articles
      using key words alogliptin, SYR-332, Nesina, Oseni, and Kazano. References of
      articles were reviewed to identify any additional sources. STUDY SELECTION AND
      DATA EXTRACTION: Articles with adequate sample sizes, evaluating clinically
      relevant end points were included. DATA SYNTHESIS: Alogliptin is a highly
      selective and potent competitive inhibitor of DPP-4. The DPP-4 enzyme rapidly
      inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide. GLP-1, which releases postprandial insulin
      in response to meals, is thought to be deficient in patients with T2DM. Studies
      evaluating the role of alogliptin in T2DM have shown significant reductions in
      blood glucose and hemoglobin A1C (A1C) levels. Alogliptin doses of 12.5 to 25 mg
      once daily reduced A1C by 0.56% to 0.59% as monotherapy. Patients given
      alogliptin in addition to other antidiabetic agentsexperienced additional A1C
      lowering of 0.4% to 0.8%. Side effects of alogliptin include nasopharyngitis,
      upper-respiratory tract infections, and headache. Alogliptin demonstrates a
      neutral effect on weight. A large trial evaluating the cardiovascular safety of
      alogliptin is currently being conducted. CONCLUSIONS: Alogliptin is the fourth
      DDP-4 inhibitor approved in the US for the treatment of T2DM. It is available
      alone (Nesina) and in fixed-dose combinations with metformin (Kazano) and
      pioglitazone (Oseni). It has no demonstrable advantages over other agents in its
      class.

PMID- 24285766
TI  - Azithromycin-induced proarrhythmia and cardiovascular death.
AB  - OBJECTIVE: To review the possible association between azithromycin and increased
      cardiovascular risk. DATA SOURCES: A literature search of MEDLINE (1946-August
      2013) was performed using the search terms macrolide, azithromycin, QT
      prolongation, cardiovascular, and torsade de pointes. Additional references were
      identified from a review of literature citations. STUDY SELECTION AND DATA
      EXTRACTION: All English-language observational studies assessing the association
      between azithromycin and QT prolongation or cardiovascular risk were evaluated.
      Case reports describing this potential association were also reviewed. DATA
      SYNTHESIS: A total of 6 case reports have shown a possible association between
      azithromycin and QT prolongation. In 3 of these cases, proarrhythmic events were
      reported. In a prospective observational study of 47 individuals with low
      cardiovascular risk, electrocardiograms were compared before and after 5 days of
      azithromycin treatment. Mild prolongation of the QTc was noted, but it was
      statistically insignificant compared with baseline. No arrhythmias were observed.
      A large observational cohort study found a small increase in cardiovascular
      deaths after azithromycin therapy, primarily among patients with high baseline
      cardiovascular risk. Conversely, a second cohort study involving a population of
      young to middle-aged adults failed to find an association. CONCLUSIONS: An
      emerging body of evidence suggests that azithromycin therapy may prolong the QT
      interval and, in rare cases, precipitate the potentially fatal arrhythmia torsade
      de pointes. Patients with additional risk factors for QT prolongation appear to
      be at highest risk, including women, elderly individuals; those with existing or
      prior history of cardiovascular disease, QT interval prolongation, hypokalemia,
      hypomagnesium, or bradycardia; and those using concomitant drugs associated with
      QT prolongation. For patients without these additional risk factors, azithromycin
      appears to be relatively safe.

PMID- 24285767
TI  - Angiotensin-converting enzyme inhibitors for intermittent claudication associated
      with peripheral arterial disease.
AB  - OBJECTIVE: To review published literature regarding the effectiveness of
      angiotensin-converting enzyme (ACE) inhibitors for managing intermittent
      claudication (IC) associated with peripheral arterial disease (PAD). DATA
      SOURCES: A search of MEDLINE/PubMed (1966-July 2013) using the MeSH terms
      intermittent claudication and angiotensin-converting enzyme inhibitors was
      conducted. Limits included articles written in English with human participants.
      Additional data were identified through bibliographic reviews. STUDY SELECTION
      AND DATA EXTRACTION: All English-language articles identified from the data
      sources were evaluated. Clinical trials and meta-analyses were included if they
      evaluated the efficacy of ACE inhibitors for improving functional capacity of
      patients with PAD with IC. In all, 9 clinical trials and 1 meta-analysis were
      identified and included for review. ACE inhibitors evaluated in the studies were
      captopril, lisinopril, perindopril, quinapril, and ramipril. DATA SYNTHESIS:
      Current medications approved for treating the symptoms and improving function in
      PAD with IC have limited efficacy. It has been suggested that ACE inhibitors may
      be effective in PAD with IC. Though data evaluating ACE inhibitors as a class in
      this patient population are conflicting, results of the largest and longest trial
      reported that ramipril increases maximum walking time and pain-free walking time
      and improves quality of life in patients with PAD with IC. CONCLUSIONS: ACE
      inhibitors may provide some relief of IC symptoms when used in patients with PAD.
      The greatest functional benefit has been seen with ramipril; it is unknown
      whether other agents in the class would show similar results. Well-controlled and
      designed studies with sufficient power and using diverse patient populations are
      needed.

PMID- 24285768
TI  - More questions than answers in ICU delirium: pressing issues for future research.
AB  - With the release of the updated pain, agitation, and delirium guidelines by the
      Society of Critical Care Medicine, a number of new and updated recommendations
      are provided regarding the pharmacological prevention and treatment of ICU
      delirium. Whereas this is important to understand the limitations of existing
      literature in interpreting the guideline recommendations, it also provides an
      opportunity to identify those areas of practice where we need further knowledge.
      We discuss 5 of the most critical questions in our view regarding pharmacological
      therapy for ICU delirium in an attempt to highlight areas of this ICU condition
      that are much deserving of further research, including the deliriogenic potential
      of dexmedetomidine, optimal sedative choices for the delirious ICU patient,
      pharmacological prophylaxis for ICU delirium, optimal treatment duration for ICU
      delirium, and the impact of pharmacotherapy on long-term cognitive outcomes in
      ICU survivors. A multitude of opportunities for further research exist in the
      above areas for clinicians and researchers interested in this ICU condition.

PMID- 24285769
TI  - Plasma renin activity testing to guide triple antirenin system drug therapy in a
      patient with difficult-to-treat hypertension.
AB  - OBJECTIVE: To report a case of difficult-to-treat hypertension ultimately managed
      with triple antirenin (anti-R) therapy using plasma renin activity (PRA) to guide
      medication selection. CASE SUMMARY: A 66-year-old white man was referred to the
      cardiology pharmacotherapy clinic for difficult-to-treat hypertension. His
      initial office blood pressure (BP) was 152/71 mm Hg on diltiazem and
      chlorthalidone. After a series of medication adjustments based on serial PRA
      measurements, the patient achieved his target BP with a regimen that included 3
      anti-R angiotensin system medications: carvedilol, valsartan, and aliskiren.
      DISCUSSION: Despite continued progress in the understanding and pharmacological
      therapy for hypertension, uncontrolled hypertension remains a major problem. The
      most common strategy to control hypertension is the stepped-care approach, with
      progressive addition of medications to eventually reach the BP goal. An
      alternative approach includes the use of PRA measurements to guide both the
      addition and removal of drugs in an attempt to effectively control BP. At times,
      this has the potential to result in a drug regimen that is incongruous with
      current guidelines and practice recommendations. However, if this results in more
      effective BP control with the same, or fewer, number of medications, it may
      represent a reasonable alternative. CONCLUSION: This case report illustrates a
      real-world application of PRA-guided therapeutics in a patient with difficult-to
      treat hypertension. It highlights how a personalized approach can lead to BP
      control with a more streamlined regimen than would likely result if a stepped
      care approach was used.

PMID- 24285770
TI  - Abnormal vaginal bleeding following pharmacist prescribing of metformin leads to
      the detection of complex endometrial hyperplasia.
AB  - OBJECTIVE: To describe a case where pharmacist prescribing of metformin therapy
      resulted in unexplained vaginal bleeding in a patient later diagnosed with
      complex endometrial hyperplasia. CASE SUMMARY: A 57-year-old woman with diagnoses
      of hypertension and dyslipidemia was assessed by a pharmacist with prescribing
      authorization for hypertension management. Cardiovascular risk assessment
      performed by the pharmacist resulted in the detection of metabolic syndrome
      confirmed by the patient's physician. The pharmacist prescribed metformin 500 mg
      twice daily for prediabetes and metabolic syndrome, resulting in vaginal bleeding
      1 week following initiation of therapy. Bleeding stopped following
      discontinuation of metformin, and recurred on retrial. The symptoms were dose
      dependent as bleeding did not occur at a dose of 500 mg once daily, but recurred
      at a total dose of 1000 mg/d. The patient was referred for physical examination
      and endometrial ultrasound and sampling, and was found to have complex
      endometrial hyperplasia. DISCUSSION: Metformin is widely used for the treatment
      of polycystic ovary syndrome as it improves ovulation and menstrual cycle
      regularity. In this case, the patient was not known to have polycystic ovary
      syndrome but was instead provided metformin for metabolic syndrome and
      hyperinsulinemia. It is believed that metformin's endocrine effects resulted in
      the sloughing of this hyperplastic tissue, prompting the pharmacist to refer the
      patient for medical assessment. This case is unique as it is the first of our
      knowledge to report a scenario where pharmacist prescribing resulted in
      facilitated detection of a previously undetected disease, highlighting that an
      expanded scope of practice for pharmacists can facilitate disease diagnosis when
      collaboration occurs among health professionals. CONCLUSIONS: Female patients
      initiated on metformin therapy should be aware that any changes to their
      menstrual cycle following metformin may indicate endometrial disease.
      Additionally, pharmacist prescribing for chronic disease management, when
      practiced collaboratively with the patient and their physician, can facilitate
      disease detection through effective referral and follow-up.

PMID- 24285771
TI  - Racial differences in self-reports of short sleep duration in an urban-dwelling
      environment.
AB  - OBJECTIVES: To explore whether there are differences in sleep duration between
      blacks and whites residing in similar urban neighborhoods and examine whether the
      relationship between sleep durations and sociodemographic and/or health indices
      are consistent for blacks and whites. METHODS: A total of 1,207 participants from
      the Healthy Aging in Neighborhoods of Disparities across the Life Span study
      (age: mean = 47, standard deviation = 8.74). Sleep duration was assessed by a
      self-report of hours of nightly sleep in the past month. Sociodemographic
      measures included age, sex, education, poverty status, and perceived neighborhood
      disorder. Health status was assessed using measures of vigilance, depression,
      perceived stress, coronary artery disease, diabetes, blood pressure, and
      inflammation. RESULTS: There were no significant racial group differences in
      sleep duration. Whites, however, were more likely than blacks to report sleep
      durations of <6/6-7 hr compared with >7 hr with increasing stress and education
      levels. Blacks were more likely than whites to report short sleep durations
      (i.e., 6-7 hr vs. >7 hr of sleep) with increasing inflammation levels.
      DISCUSSION: Although racial disparities in sleep duration are minimized when the
      environment is equivalent between blacks and whites, the underlying demographic
      and health explanations for short sleep durations may vary between whites and
      blacks.

PMID- 24285772
TI  - Surrogacy assessment using principal stratification when surrogate and outcome
      measures are multivariate normal.
AB  - In clinical trials, a surrogate outcome variable (S) can be measured before the
      outcome of interest (T) and may provide early information regarding the treatment
      (Z) effect on T. Using the principal surrogacy framework introduced by Frangakis
      and Rubin (2002. Principal stratification in causal inference. Biometrics 58, 21
      29), we consider an approach that has a causal interpretation and develop a
      Bayesian estimation strategy for surrogate validation when the joint distribution
      of potential surrogate and outcome measures is multivariate normal. From the
      joint conditional distribution of the potential outcomes of T, given the
      potential outcomes of S, we propose surrogacy validation measures from this
      model. As the model is not fully identifiable from the data, we propose some
      reasonable prior distributions and assumptions that can be placed on weakly
      identified parameters to aid in estimation. We explore the relationship between
      our surrogacy measures and the surrogacy measures proposed by Prentice (1989.
      Surrogate endpoints in clinical trials: definition and operational criteria.
      Statistics in Medicine 8, 431-440). The method is applied to data from a macular
      degeneration study and an ovarian cancer study. 

PMID- 24285773
TI  - Bayesian inference for longitudinal data with non-parametric treatment effects.
AB  - We consider inference for longitudinal data based on mixed-effects models with a
      non-parametric Bayesian prior on the treatment effect. The proposed non
      parametric Bayesian prior is a random partition model with a regression on
      patient-specific covariates. The main feature and motivation for the proposed
      model is the use of covariates with a mix of different data formats and possibly
      high-order interactions in the regression. The regression is not explicitly
      parameterized. It is implied by the random clustering of subjects. The motivating
      application is a study of the effect of an anticancer drug on a patient's blood
      pressure. The study involves blood pressure measurements taken periodically over
      several 24-h periods for 54 patients. The 24-h periods for each patient include a
      pretreatment period and several occasions after the start of therapy. 

PMID- 24285774
TI  - Dry eyes, are we getting anywhere?

PMID- 24285775
TI  - Increased kappa-opioid receptor expression and function during chronic visceral
      hypersensitivity.

PMID- 24285776
TI  - Hearing loss in Thai naval officers of coastal patrol crafts.
AB  - This cross-sectional study aimed to examine the prevalence of hearing loss and
      its risk factors among Thai naval officers. The subjects consisted of 149 males
      who were asked to complete a questionnaire. Audiometric threshold testing was
      performed at the audiometric frequencies of 0.5, 1, 2, 4, and 8 kHz. The noise
      levels and the organic solvent concentrations in the working environment were
      measured on a common type of gun boat. The findings revealed that 39.6% of naval
      officers had hearing loss. The noise level (LAeq) was 100.6 dB in the engine
      room. The organic solvent concentrations were less than the occupational exposure
      limit for organic solvents. Multiple logistic regression analysis indicated 2
      factors were significantly associated with hearing loss. They were age and
      service experience. The results suggest that the Thai navy should develop a
      hearing conservation program for naval officers on coastal patrol crafts.

PMID- 24285777
TI  - Correlation between oral health and Child-OIDP index in 12- and 15-year-old
      children from Modinagar, India.
AB  - To investigate the relationship between oral health measures and oral health
      related quality of life using the Child-Oral Impact on Daily Performance index
      among school children of Modinagar. A cross-sectional analytical study was
      conducted on 900 school children aged 12 and 15 years in Modinagar, India.
      Children were interviewed about sociodental impacts on quality of life and
      examined for their normative treatment need for dental caries, traumatic dental
      injuries, and dentofacial anomalies. Frequency distributions for bivariate
      analysis and logistic regression for multivariate analysis were used for
      statistical analysis. Prevalence of oral impacts was high (60%), with a mean
      score of 2.49 +/- 3.92. A significant association (P <= .05) was observed in oral
      impacts on daily performances with age, presence of dental caries, traumatic
      injuries, and dentofacial anomalies score. A strong association between clinical
      dental indicators and oral impacts in children showed eating followed by cleaning
      of teeth and smiling as the most commonly affected daily performances. 

PMID- 24285778
TI  - Predictors of handgrip strength among adults of a rural community in Malaysia.
AB  - Handgrip strength is useful for screening the nutritional status of adult
      population as it is strongly associated with physical disabilities and mortality.
      Therefore, we aimed to determine the predictors of handgrip strength among adults
      of a rural community in Malaysia using a cross-sectional study design with
      multistage sampling. All adults aged 30 years and older from 1250 households were
      invited to our study. Structured questionnaire on sociodemographic
      characteristics, medical history, occupation history, lifestyle practices, and
      measurements, including anthropometry and handgrip strength were taken. There
      were 2199 respondents with 55.2% females and majority were of Malay ethnicity.
      Their mean (standard deviation) age was 53.4 (13.2) years. The response rate for
      handgrip strength was 94.2%. Females had significantly lower handgrip strength
      than males (P < .05). In the multiple linear regression models, significant
      predictors of handgrip strength for males were age, height, job groups, and
      diabetes, while for females, the significant predictors were age, weight, height,
      and diabetes. 

PMID- 24285779
TI  - Estimation of Vietnam national burden of disease 2008.
AB  - Burden of disease has been used to assess population health status. This article
      presents the first estimations of burden of disease in Vietnam in 2008 using
      disability-adjusted life years (DALYs). DALYs were calculated using the Global
      Burden of Disease (GBD) methods. Incidence, prevalence of diseases, and causes of
      death was extracted from Vietnam data. Disability weights were borrowed from GBD
      and Dutch research. In 2008, the total burden of disease in Vietnam was 12.3
      million DALYs. Noncommunicable diseases dominated the total burden of diseases in
      Vietnam, accounting for 71% of the total burden, and cardiovascular disease was
      the leading cause group of premature death. While pneumonia was an important
      cause of burden in Vietnamese children, stroke and depression were the main
      causes of disease burden among adults. The study provides a snapshot of
      Vietnamese health status and offers guidance for health policymaking in Vietnam. 

PMID- 24285780
TI  - Predictors of outcomes of recovery following total hip replacement surgery: A
      prospective study.
AB  - OBJECTIVES: To investigate psychosocial and biomedical outcomes following total
      hip replacement (THR) and to identify predictors of recovery from THR. METHODS:
      Patients with osteoarthritis (OA) on the waiting list for primary THR in North
      West England were assessed pre-operatively and at six and 12 months post
      operatively to investigate psychosocial and biomedical outcomes. Psychosocial
      outcomes were anxiety and depression, social support and health-related quality
      of life (HRQoL). Biomedical outcomes were pain, physical function and stiffness.
      The primary outcome was the Short-Form 36 (SF-36) Health Survey Total Physical
      Function. Potential predictors of outcome were age, sex, body mass index,
      previous joint replacement, involvement in the decision for THR, any
      comorbidities, any complications, type of medication, and pre-operative ENRICHD
      Social Support Instrument score, Hospital Anxiety and Depression scores and
      Western Ontario and McMaster Universities osteoarthritis index score. RESULTS:
      The study included 206 patients undergoing THR. There were 88 men and 118 women
      with a mean age of 66.3 years (sd 10.4;36 to 89). Pain, stiffness and physical
      function, severity of OA, HRQoL, anxiety and depression all improved
      significantly from pre-operative to 12-month assessment (all p < 0.001), with the
      greatest improvement occurring in the first six months (all p < 0.001). The
      predictors that were found to influence recovery six months after THR were: pain
      (p < 0.001), anxiety (p = 0.034), depression (p = 0.001), previous joint
      replacement (p = 0.006) and anti-inflammatory drugs (p = 0.012). CONCLUSIONS: The
      study identified the key psychosocial and biomedical predictors of recovery
      following THR. By identifying these predictors, we are able to identify and
      provide more support for patients at risk of poor recovery following THR. Cite
      this article: Bone Joint Res 2013;2:248-54.

PMID- 24285781
TI  - The motivating operation and negatively reinforced problem behavior: a systematic
      review.
AB  - The concept of motivational operations exerts an increasing influence on the
      understanding and assessment of problem behavior in people with intellectual and
      developmental disability. In this systematic review of 59 methodologically robust
      studies of the influence of motivational operations in negative reinforcement
      paradigms in this population, we identify themes related to situational and
      biological variables that have implications for assessment, intervention, and
      further research. There is now good evidence that motivational operations of
      differing origins influence negatively reinforced problem behavior, and that
      these might be subject to manipulation to facilitate favorable outcomes. There is
      also good evidence that some biological variables warrant consideration in
      assessment procedures as they predispose the person's behavior to be influenced
      by specific motivational operations. The implications for assessment and
      intervention are made explicit with reference to variables that are open to
      manipulation or that require further research and conceptualization within causal
      models. 

PMID- 24285782
TI  - Patellofemoral osteoarthritis is prevalent and associated with worse symptoms and
      function after hamstring tendon autograft ACL reconstruction.
AB  - OBJECTIVES: To evaluate the compartmental distribution of knee osteoarthritis
      (OA) after anterior cruciate ligament reconstruction (ACLR), to determine if
      patellofemoral or tibiofemoral OA is more strongly associated with knee symptoms
      and function, and to evaluate the contribution of associated injuries and
      surgical delay to the development of OA. METHODS: This cross-sectional study
      recruited 70 participants who underwent hamstring tendon (HT) ACLR 5-10 years
      previously. Radiographic OA was assessed according to the Osteoarthritis Research
      Society International (OARSI) criteria. Knee symptoms were assessed with the Knee
      Injury and Osteoarthritis Outcome Score (KOOS) and Anterior Knee Pain Scale
      (AKPS), while function was assessed with three lower limb tasks (hop-for
      distance, one-leg rise and side-hop). Multivariate and binary logistic regression
      analyses were performed to assess the relationship between OA and
      symptomatic/functional outcomes and associated injuries/surgical delay,
      respectively. RESULTS: Radiographic OA was observed in the patellofemoral (47%)
      and tibiofemoral joints (31%). Pain, symptoms and quality of life on the KOOS and
      the AKPS were associated with severity of patellofemoral OA (standardised
      regression coefficient (beta)=-0.3 to -0.5, p=0.001-0.042), whereas only the KOOS
      pain subscale was associated with tibiofemoral OA (beta=-0.3, p=0.037). For each
      functional task, greater patellofemoral OA severity was associated with worse
      performance, independent of tibiofemoral OA severity (beta=-0.3 to -0.4, p=0.001
      0.026). Medial meniscal and patellofemoral chondral lesions at surgery were
      associated with tibiofemoral and patellofemoral OA development at follow-up,
      respectively, while a longer surgery delay was associated with patellofemoral OA.
      CONCLUSIONS: Patellofemoral OA is common following HT ACLR and is associated with
      worse knee-related symptoms, including anterior knee pain, and decreased
      functional performance.

PMID- 24285783
TI  - Epidemiology, identification, treatment and return to play of musculoskeletal
      based ice hockey injuries.
AB  - Ice hockey is a high contact sport where players are inherently at an increased
      risk for traumatic and time-loss injury. With its increasing popularity and high
      incidence of injury, further research is necessary to understand the risks and
      injuries associated with the sport and to develop performance-based outcome
      measures to guide return to play. This review, tailored to the practicing sports
      medicine team physician, focuses on the stepwise identification, treatment, time
      loss, return to play and subsequent risk of injury for the most common areas of
      injury: the head, shoulder, hip and knee. Injuries were categorised into upper
      and lower extremity with an emphasis on glenohumeral and acromioclavicular joint
      injuries, femoroacetabular impingement, medial collateral ligament tears, and
      high ankle sprains. With return to play a primary goal for these high-level
      athletes, recovery in ice hockey becomes a complex issue with efficient protocols
      tailored to the requirements of the sport vital to the athlete and clinician
      alike. By reviewing the treatments and sport-specific care, athletes can be
      better managed with the ultimate goal of returning to their preinjury level of
      play. LEVEL OF EVIDENCE: Level IV.

PMID- 24285784
TI  - Influence of smoking cigarettes on cerebral blood flow parameters.
AB  - INTRODUCTION: While chronic cigarette smoking can lead to increased risk of
      stroke, the acute effects of smoking have not been established. We studied the
      changes in blood flow parameters in the major cerebral arteries caused by smoking
      one cigarette. METHOD: Using transcranial color-coded sonography (TCCS), we
      studied the anterior cerebral artery (ACA), middle cerebral artery (MCA),
      posterior cerebral artery (PCA), and the internal carotid artery (ICA) of 36
      healthy male volunteers before and after they smoked one cigarette. RESULTS:
      Blood flow velocity increased to a different degree in all but one of the
      arteries examined after participants smoked a single cigarette: The end diastolic
      velocity increased significantly by 7.8% in the PCA, 8% in the ACA, and 14.4% in
      the MCA. The peak systolic velocity increased significantly by 7.5% in the MCA.
      Blood flow velocity remained unchanged in the ICA only. Blood pressure and heart
      rate increased as did the flow velocity ratio for the MCA/ICA. The pulsatility
      index decreased after smoking from 0.92 +/- 0.13 to 0.87 +/- 0.14 in the MCA,
      0.93 +/- 0.15 to 0.87 +/- 0.13 in the ACA, and 0.95 +/- 0.17 to 0.89 +/- 0.16 in
      the PCA. CONCLUSIONS: The results suggest that the direct effect of smoking on
      cerebral circulation includes peripheral vasodilatation with possible
      constriction of the main trunk of the basal cerebral arteries.

PMID- 24285785
TI  - Private patients are more likely to have a caesarean section, finds study.

PMID- 24285786
TI  - The Arabidopsis NAC transcription factor ANAC096 cooperates with bZIP-type
      transcription factors in dehydration and osmotic stress responses.
AB  - Multiple transcription factors (TFs) play essential roles in plants under abiotic
      stress, but how these multiple TFs cooperate in abiotic stress responses remains
      largely unknown. In this study, we provide evidence that the NAC (for NAM,
      ATAF1/2, and CUC2) TF ANAC096 cooperates with the bZIP-type TFs ABRE binding
      factor and ABRE binding protein (ABF/AREB) to help plants survive under
      dehydration and osmotic stress conditions. ANAC096 directly interacts with ABF2
      and ABF4, but not with ABF3, both in vitro and in vivo. ANAC096 and ABF2
      synergistically activate RD29A transcription. Our genome-wide gene expression
      analysis revealed that a major proportion of abscisic acid (ABA)-responsive genes
      are under the transcriptional regulation of ANAC096. We found that the
      Arabidopsis thaliana anac096 mutant is hyposensitive to exogenous ABA and shows
      impaired ABA-induced stomatal closure and increased water loss under dehydration
      stress conditions. Furthermore, we found the anac096 abf2 abf4 triple mutant is
      much more sensitive to dehydration and osmotic stresses than the anac096 single
      mutant or the abf2 abf4 double mutant. Based on these results, we propose that
      ANAC096 is involved in a synergistic relationship with a subset of ABFs for the
      transcriptional activation of ABA-inducible genes in response to dehydration and
      osmotic stresses.

PMID- 24285787
TI  - Regulation of FLOWERING LOCUS T by a microRNA in Brachypodium distachyon.
AB  - The highly conserved florigen gene FLOWERING LOCUS T (FT) functions at the core
      of the flowering pathways. Extensive studies have examined the transcriptional
      regulation of FT; however, other layers of FT regulation remain unclear. Here, we
      identified miR5200 a Pooideae-specific microRNA that is expressed in leaves and
      targets Brachypodium distachyon FT orthologs for mRNA cleavage. miR5200 was
      abundantly expressed in plants grown under short-day (SD) conditions but was
      dramatically repressed in plants transferred to long-day (LD) conditions. We also
      found that the epigenetic chromatin status, specifically the levels of histone
      methylation marks, at miR5200 precursor loci changed in response to daylength.
      Moreover, artificial interruption of miR5200 activity by target mimicry in B.
      distachyon altered flowering time in SD but not in LD conditions, suggesting that
      miR5200 functions in photoperiod-mediated flowering time regulation. Together,
      these findings illustrate a posttranscriptional regulation mechanism of FT and
      provide insights into understanding of the multiple concerted pathways for
      flowering time control in plants.

PMID- 24285788
TI  - Two Rumex species from contrasting hydrological niches regulate flooding
      tolerance through distinct mechanisms.
AB  - Global climate change has increased flooding events, which affect both natural
      vegetation dynamics and crop productivity. The flooded environment is lethal for
      most plant species because it restricts gas exchange and induces an energy and
      carbon crisis. Flooding survival strategies have been studied in Oryza sativa, a
      cultivated monocot. However, our understanding of plant adaptation to natural
      flood-prone environments remains scant, even though wild plants represent a
      valuable resource of tolerance mechanisms that could be used to generate stress
      tolerant crops. Here we identify mechanisms that mediate the distinct flooding
      survival strategies of two related wild dicot species: Rumex palustris and Rumex
      acetosa. Whole transcriptome sequencing and metabolite profiling reveal flooding
      induced metabolic reprogramming specific to R. acetosa. By contrast, R. palustris
      uses the early flooding signal ethylene to increase survival by regulating shade
      avoidance and photomorphogenesis genes to outgrow submergence and by priming
      submerged plants for future low oxygen stress. These results provide molecular
      resolution of flooding survival strategies of two species occupying distinct
      hydrological niches. Learning how these contrasting flood adaptive strategies
      evolved in nature will be instrumental for the development of stress-tolerant
      crop varieties that deliver enhanced yields in a changing climate.

PMID- 24285790
TI  - Calmodulin methylation: another layer of regulation in calcium signaling.

PMID- 24285789
TI  - Gene coexpression analysis reveals complex metabolism of the monoterpene alcohol
      linalool in Arabidopsis flowers.
AB  - The cytochrome P450 family encompasses the largest family of enzymes in plant
      metabolism, and the functions of many of its members in Arabidopsis thaliana are
      still unknown. Gene coexpression analysis pointed to two P450s that were
      coexpressed with two monoterpene synthases in flowers and were thus predicted to
      be involved in monoterpenoid metabolism. We show that all four selected genes,
      the two terpene synthases (TPS10 and TPS14) and the two cytochrome P450s
      (CYP71B31 and CYP76C3), are simultaneously expressed at anthesis, mainly in upper
      anther filaments and in petals. Upon transient expression in Nicotiana
      benthamiana, the TPS enzymes colocalize in vesicular structures associated with
      the plastid surface, whereas the P450 proteins were detected in the endoplasmic
      reticulum. Whether they were expressed in Saccharomyces cerevisiae or in N.
      benthamiana, the TPS enzymes formed two different enantiomers of linalool: (-)
      (R)-linalool for TPS10 and (+)-(S)-linalool for TPS14. Both P450 enzymes
      metabolize the two linalool enantiomers to form different but overlapping sets of
      hydroxylated or epoxidized products. These oxygenated products are not emitted
      into the floral headspace, but accumulate in floral tissues as further converted
      or conjugated metabolites. This work reveals complex linalool metabolism in
      Arabidopsis flowers, the ecological role of which remains to be determined.

PMID- 24285792
TI  - Breaking down the complex regulatory web underlying lignin biosynthesis.

PMID- 24285791
TI  - RETINOBLASTOMA-RELATED protein stimulates cell differentiation in the Arabidopsis
      root meristem by interacting with cytokinin signaling.
AB  - Maintenance of mitotic cell clusters such as meristematic cells depends on their
      capacity to maintain the balance between cell division and cell differentiation
      necessary to control organ growth. In the Arabidopsis thaliana root meristem, the
      antagonistic interaction of two hormones, auxin and cytokinin, regulates this
      balance by positioning the transition zone, where mitotically active cells lose
      their capacity to divide and initiate their differentiation programs. In animals,
      a major regulator of both cell division and cell differentiation is the tumor
      suppressor protein RETINOBLASTOMA. Here, we show that similarly to its homolog in
      animal systems, the plant RETINOBLASTOMA-RELATED (RBR) protein regulates the
      differentiation of meristematic cells at the transition zone by allowing mRNA
      accumulation of AUXIN RESPONSE FACTOR19 (ARF19), a transcription factor involved
      in cell differentiation. We show that both RBR and the cytokinin-dependent
      transcription factor ARABIDOPSIS RESPONSE REGULATOR12 are required to activate
      the transcription of ARF19, which is involved in promoting cell differentiation
      and thus root growth.

PMID- 24285793
TI  - Small RNAs and the big decisions: MicroRNA regulation of photoperiodic flowering
      in Brachypodium distachyon.

PMID- 24285794
TI  - Calmodulin-mediated signal transduction pathways in Arabidopsis are fine-tuned by
      methylation.
AB  - Calmodulin N-methyltransferase (CaM KMT) is an evolutionarily conserved enzyme in
      eukaryotes that transfers three methyl groups to a highly conserved lysyl residue
      at position 115 in calmodulin (CaM). We sought to elucidate whether the
      methylation status of CaM plays a role in CaM-mediated signaling pathways by gene
      expression analyses of CaM KMT and phenotypic characterization of Arabidopsis
      thaliana lines wherein CaM KMT was overexpressed (OX), partially silenced, or
      knocked out. CaM KMT was expressed in discreet spatial and tissue-specific
      patterns, most notably in root tips, floral buds, stamens, apical meristems, and
      germinating seeds. Analysis of transgenic plants with genetic dysfunction in CaM
      KMT revealed a link between the methylation status of CaM and root length. Plants
      with suppressed CaM methylation had longer roots and CaM KMT OX lines had shorter
      roots than wild type (Columbia-0). CaM KMT was also found to influence the root
      radial developmental program. Protein microarray analyses revealed a number of
      proteins with specificity for methylated forms of CaM, providing candidate
      functional intermediates between the observed phenotypes and the target pathways.
      This work demonstrates that the functionality of the large CaM family in plants
      is fine-tuned by an overarching methylation mechanism.

PMID- 24285795
TI  - A genomics approach to deciphering lignin biosynthesis in switchgrass.
AB  - It is necessary to overcome recalcitrance of the biomass to saccharification
      (sugar release) to make switchgrass (Panicum virgatum) economically viable as a
      feedstock for liquid biofuels. Lignin content correlates negatively with sugar
      release efficiency in switchgrass, but selecting the right gene candidates for
      engineering lignin biosynthesis in this tetraploid outcrossing species is not
      straightforward. To assist this endeavor, we have used an inducible switchgrass
      cell suspension system for studying lignin biosynthesis in response to exogenous
      brassinolide. By applying a combination of protein sequence phylogeny with whole
      genome microarray analyses of induced cell cultures and developing stem internode
      sections, we have generated a list of candidate monolignol biosynthetic genes for
      switchgrass. Several genes that were strongly supported through our
      bioinformatics analysis as involved in lignin biosynthesis were confirmed by gene
      silencing studies, in which lignin levels were reduced as a result of targeting a
      single gene. However, candidate genes encoding enzymes involved in the early
      steps of the currently accepted monolignol biosynthesis pathway in dicots may
      have functionally redundant paralogues in switchgrass and therefore require
      further evaluation. This work provides a blueprint and resources for the
      systematic genome-wide study of the monolignol pathway in switchgrass, as well as
      other C4 monocot species.

PMID- 24285798
TI  - Intestinal malrotation and volvulus in infants and children.

PMID- 24285796
TI  - Pathogen-triggered ethylene signaling mediates systemic-induced susceptibility to
      herbivory in Arabidopsis.
AB  - Multicellular eukaryotic organisms are attacked by numerous parasites from
      diverse phyla, often simultaneously or sequentially. An outstanding question in
      these interactions is how hosts integrate signals induced by the attack of
      different parasites. We used a model system comprised of the plant host
      Arabidopsis thaliana, the hemibiotrophic bacterial phytopathogen Pseudomonas
      syringae, and herbivorous larvae of the moth Trichoplusia ni (cabbage looper) to
      characterize mechanisms involved in systemic-induced susceptibility (SIS) to T.
      ni herbivory caused by prior infection by virulent P. syringae. We uncovered a
      complex multilayered induction mechanism for SIS to herbivory. In this mechanism,
      antiherbivore defenses that depend on signaling via (1) the jasmonic acid
      isoleucine conjugate (JA-Ile) and (2) other octadecanoids are suppressed by
      microbe-associated molecular pattern-triggered salicylic acid (SA) signaling and
      infection-triggered ethylene signaling, respectively. SIS to herbivory is, in
      turn, counteracted by a combination of the bacterial JA-Ile mimic coronatine and
      type III virulence-associated effectors. Our results show that SIS to herbivory
      involves more than antagonistic signaling between SA and JA-Ile and provide
      insight into the unexpectedly complex mechanisms behind a seemingly simple trade
      off in plant defense against multiple enemies.

PMID- 24285799
TI  - Commentary: Patients will need knowledgeable guidance.

PMID- 24285797
TI  - Catalase and NO CATALASE ACTIVITY1 promote autophagy-dependent cell death in
      Arabidopsis.
AB  - Programmed cell death often depends on generation of reactive oxygen species,
      which can be detoxified by antioxidative enzymes, including catalases. We
      previously isolated catalase-deficient mutants (cat2) in a screen for resistance
      to hydroxyurea-induced cell death. Here, we identify an Arabidopsis thaliana
      hydroxyurea-resistant autophagy mutant, atg2, which also shows reduced
      sensitivity to cell death triggered by the bacterial effector avrRpm1. To test if
      catalase deficiency likewise affected both hydroxyurea and avrRpm1 sensitivity,
      we selected mutants with extremely low catalase activities and showed that they
      carried mutations in a gene that we named NO CATALASE ACTIVITY1 (NCA1). nca1
      mutants showed severely reduced activities of all three catalase isoforms in
      Arabidopsis, and loss of NCA1 function led to strong suppression of RPM1
      triggered cell death. Basal and starvation-induced autophagy appeared normal in
      the nca1 and cat2 mutants. By contrast, autophagic degradation induced by avrRpm1
      challenge was compromised, indicating that catalase acted upstream of immunity
      triggered autophagy. The direct interaction of catalase with reactive oxygen
      species could allow catalase to act as a molecular link between reactive oxygen
      species and the promotion of autophagy-dependent cell death.

PMID- 24285800
TI  - British women are engaging in greater variety of sexual practices.

PMID- 24285801
TI  - Supervised training and home-based rehabilitation in patients with stabilized
      ankylosing spondylitis on TNF inhibitor treatment: a controlled clinical trial
      with a 12-month follow-up.
AB  - OBJECTIVE: To assess the 12-month's follow-up effects on pain, mobility, and
      physical function outcomes of a supervised training and home-based rehabilitation
      for ankylosing spondylitis patients stabilized with TNF-inhibitor therapy.
      DESIGN: Controlled clinical trial (sequentially determined allocation) with 12
      months' follow-up. SETTING: Patients' homes. SUBJECTS: A total of 69 subjects
      were allocated to either a rehabilitation programme (rehabilitation group, n =
      22), an educational-behavioural programme (educational group, n = 24), and to
      neither programme (control group, n = 23). INTERVENTIONS: Rehabilitation
      programme included supervised training and home exercises (stretching,
      strengthening, aerobic, chest, and spine/hip joint flexibility exercises);
      educational-behavioural programme included information on ankylosing spondylitis,
      pain and stress mechanisms, and control. MAIN MEASURES: Spinal pain intensity,
      Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis
      Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, chest
      expansion, and cervical and lumbar spine active range of motion measured by a
      pocket goniometer. RESULTS: At baseline, the three groups exhibited comparable
      demographic characteristics and basal evaluations. Intra-group changes in the
      rehabilitation group from baseline to 12 months yielded statistically significant
      gains (p < 0.05) for all outcomes. At 12-months follow-up, compared with the
      control and educational-behavioural, the rehabilitation group exhibited
      significant differences in chest expansion (p = 0.001 and p < 0.001), Bath
      Ankylosing Spondylitis Disease Activity Index (p = 0.012 and p = 0.050), and in
      some goniometric measurements as cervical rotation (p = 0.007 and p = 0.014),
      toraco-lumbar rotation (p = 0.009 and p = 0.050), and total cervical movements (p
      = 0.009 and p = 0.001). CONCLUSION: In comparison with the educational
      behavioural programme or no intervention, supervised training and home exercises
      improved long-term outcome in patients with ankylosing spondylitis.

PMID- 24285802
TI  - A large left atrial myxoma causing multiple cerebral infarcts.
AB  - A 52-year-old man presented with a history of sudden onset diplopia. On
      neurological examination, the only abnormality was a right-sided oculomotor
      (third nerve) palsy. A brain CT was performed and reported as showing no
      abnormality. He was discharged to be investigated as an outpatient. He presented
      1 month later with a new expressive dysphasia and confusional state. MRI was
      performed which revealed multiple cerebral infarcts. He was discharged on
      secondary stroke prevention medication. Six months elapsed, before a
      transthoracic echocardiogram was performed. This showed a large left atrial
      myxoma. The patient underwent an emergency resection and made a good
      postoperative recovery. This case report showed the importance of considering a
      cardiogenic source of emboli in patients who present with cerebral infarcts.
      Performing echocardiography early will help to detect treatable conditions such
      as atrial myxoma, and prevent further complications. 

PMID- 24285803
TI  - Tentorial dural arteriovenous fistula manifesting as contralateral trigeminal
      neuralgia: resolution after transarterial Onyx embolization.
AB  - Tentorial dural arteriovenous fistula (DAVF) as a cause of trigeminal neuralgia
      is extremely rare. Although less than 10 cases have been reported in the
      literature, all cases presented with ipsilateral trigeminal neuralgia. Here we
      report a unique case of tentorial DAVF manifesting as contralateral trigeminal
      neuralgia. A 58-year-old man presented with right-sided trigeminal neuralgia.
      Cerebral angiography revealed a left tentorial DAVF and the MR imaging
      demonstrated a variceal venous dilatation occupying the left lateral pontine
      cistern and multiple venous flow voids adjacent to the right trigeminal nerve
      root entry zone. Transarterial Onyx embolization resulted in near complete
      obliteration of the fistula with immediate resolution of facial pain. The patient
      remains symptom free and without evidence of recurrence during 9 months of follow
      up. Transarterial Onyx embolization may be an effective treatment modality for
      such an usual case. 

PMID- 24285804
TI  - An uncommon Essex-Lopresti fracture dislocation with radial displacement in
      distal direction: diagnosis and surgical treatment of a rare case.
AB  - Essex-Lopresti injuries are rare and present a clinical challenge. Incomplete
      diagnosis and treatment can lead to long-term instability, pain and functional
      impairment. We report on a clinical case of proximal radioulnar joint (PRUJ) and
      distal radioulnar joint (DRUJ) dislocation with unusual distal radial
      displacement and associated radial head shear fracture. The case was managed with
      closed reduction of the PRUJ and DRUJ followed by open reduction and fixation of
      the radial head. A high index of suspicion with thorough examination of the
      elbow, forearm and wrist and comprehensive imaging was important in reaching a
      complete diagnosis for appropriate treatment. Anatomical reduction of the PRUJ
      and DRUJ is essential to achieve optimal functional outcomes. Six months
      following the injury the patient made a satisfactory recovery with full range of
      movement; however, she continued to have mild to moderate general and moderate
      work-related disability. 

PMID- 24285805
TI  - Non-invasive, low-grade papillary urothelial carcinoma in the urachus.
AB  - The urachus is a duct connecting the allantois with the fetal bladder, forming
      the median umbilical ligament; it usually obliterates during fetal life.
      Carcinomas arising from urachal remnants are rare but associated with a poor
      prognosis. We present one case of non-invasive urachal papillary urothelial
      carcinoma, and through a systematic literature search, we identified 12
      additional cases of urachal urothelial carcinoma reported in English literature
      in the past 20 years. The cases were compared according to the Sheldon Staging
      System and the Mayo Staging System presented by Ashley et al in 2006, and both
      Staging Systems tend to predict clinical outcome. The urachal carcinoma is an
      important differential diagnosis in patients presenting with haematuria or an
      infraumbilical mass, because the symptoms may be sparse and diagnosis at an early
      stage is essential for successful treatment. 

PMID- 24285806
TI  - Discordant monozygotic total colonic Hirschsprung's disease presenting with
      neonatal isolated ileal perforation.

PMID- 24285807
TI  - Chilblain lupus erythematosus.
AB  - Chilblain lupus erythematosus is a rare form of chronic cutaneous lupus
      erythematosus. It is characterised by purple plaques/nodules and oedematous skin
      mainly around the acral regions of the body, which are most exposed to the cold.
      In this paper we report a case of chilblain lupus erythematosus that was
      diagnosed using the Mayo Clinic Diagnostic Criteria and its successful treatment
      with hydroxychloroquine. 

PMID- 24285808
TI  - Diagnostic difficulties delaying treatment in a patient with fibrous dysplasia of
      the right femur.

PMID- 24285809
TI  - Ventriculopleural shunt CSF pseudocyst presenting as an anterior mediastinal
      mass.

PMID- 24285810
TI  - Imaging in Fahr's disease: how CT and MRI differ?

PMID- 24285811
TI  - Juvenile aggressive cemento-ossifying fibroma of the sphenoid sinus with
      proptosis: a surgical dilemma.
AB  - The term fibro-osseous lesion has currently grown in popularity as an overall
      designation for a number of rare, histologically benign head and neck lesions
      that are made up of bone, fibrous tissue and cementum. Cemento-ossifying fibroma
      is a variant of cementifying fibroma and is a fibro-osseous disease. They are
      usually small innocuous lesions which follow a slow benign course and are
      commonly seen in the skull bone rather than the sphenoid. It is rare for these
      tumours to attain large size, behave aggressively, destroy bone and require a
      radical surgery. One such rapidly growing juvenile cemento-ossifying lesion of
      sphenoid in our 10-year-old young patient causing proptosis and impaired vision
      is reported here because of its uncommon nature and its surgical dilemma.
      Selection of surgical approach to resect this tumour becomes difficult because it
      is deeply seated and needs a multidisciplinary approach. 

PMID- 24285812
TI  - Recognising serious umbilical cord anomalies.
AB  - Umbilical vessel catheterisation is a common intervention in neonatal care. Many
      complications are recognised, some of which are life-threatening. We report the
      case of a term neonate who was compromised at birth following antepartum
      haemorrhage with evidence of multiorgan ischaemic injury. Following resuscitation
      and umbilical vessel catheterisation, she developed pneumoperitoneum. At
      laparotomy, a patent vitellointestinal duct was identified and resected.
      Intestinal perforation was found in the duct wall, most plausibly explained by
      the unintentional catheterisation of the duct via the umbilicus. Learning to
      recognise umbilical cord anomalies, such as patent vitellointestinal duct, can be
      simple and could prevent potentially serious complications. 

PMID- 24285813
TI  - Chemotherapy-resistant breast implant-associated anaplastic large cell lymphoma.
AB  - A 43-year-old woman presented with a few weeks' history of discomfort and
      swelling in her left breast. She had undergone bilateral breast augmentation 8
      years previously. There were no risk factors for breast cancer. Clinical
      examination, mammography and breast ultrasound revealed a large left breast mass
      adjacent to the breast implant with enlarged axillary lymph nodes. Owing to
      diagnostic uncertainty, core biopsies were sent to a specialist unit which
      confirmed breast implant-associated anaplastic large cell lymphoma with involved
      lymph nodes. Staging investigations confirmed no distant disease. The lymphoma
      multidisciplinary team recommended cyclophosphamide, doxorubicin, vincristine and
      prednisone chemotherapy, followed by implant removal and local radiotherapy.
      However, the patient's disease progressed on first-line, and then second-line
      chemotherapy. She therefore had a mastectomy and axillary node clearance followed
      by radiotherapy, with a planned delayed left breast reconstruction and removal of
      the right breast implant. 

PMID- 24285814
TI  - An unusually extensive internal jugular vein thrombosis.

PMID- 24285815
TI  - An unusual distended abdomen.

PMID- 24285816
TI  - Absence of an important vaccine and diagnostic target in carriage- and disease
      related nontypeable Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi)-associated disease is a major health
      problem globally. Whole-genome sequence analysis identified the absence of hpd
      genes encoding Haemophilus protein D in 3 of 16 phylogenetically distinct NTHi
      isolates. This novel finding is of potential clinical significance, as protein D
      and hpd represent important NTHi vaccine antigen and diagnostic targets,
      respectively. 

PMID- 24285817
TI  - Development of a highly sensitive and specific blastomycosis antibody enzyme
      immunoassay using Blastomyces dermatitidis surface protein BAD-1.
AB  - Serologic tests for antibodies to Blastomyces dermatitidis are not thought to be
      useful for the diagnosis of blastomycosis, in part due to the low sensitivity of
      immunodiffusion and complement fixation. Earlier studies have shown that the
      enzyme immunoassay improves the sensitivity of antibody detection for the
      diagnosis of blastomycosis. Microplates coated with the B. dermatitidis surface
      protein BAD-1 were used for testing sera from patients with proven blastomycosis
      or histoplasmosis and controls. Semiquantification was accomplished by using
      standards containing human anti-B. dermatitidis antibodies. The antibodies were
      detected in 87.8% of the patients with blastomycosis by the enzyme immunoassay
      compared to 15.0% by immunodiffusion. The specificities were 99.2% for patients
      with nonfungal infections and healthy subjects and 94.0% for patients with
      histoplasmosis. The results were highly reproducible on repeat testing. When
      combined with antigen testing, antibody testing improved the sensitivity from
      87.8% to 97.6%. Enzyme immunoassay detection of antibodies against BAD-1 is
      highly specific, has greatly improved sensitivity over immunodiffusion, and may
      identify cases with negative results by antigen testing. This assay has the
      potential to aid in the diagnosis of blastomycosis. 

PMID- 24285818
TI  - Identification of immunological biomarkers which may differentiate latent
      tuberculosis from exposure to environmental nontuberculous mycobacteria in
      children.
AB  - A positive gamma interferon (IFN-gamma) response to Mycobacterium tuberculosis
      early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10)
      has been taken to indicate latent tuberculosis (TB) infection, but it may also be
      due to exposure to environmental nontuberculous mycobacteria in which ESAT-6
      homologues are present. We assessed the immune responses to M. tuberculosis ESAT
      6 and cross-reactive responses to ESAT-6 homologues of Mycobacterium avium and
      Mycobacterium kansasii. Archived culture supernatant samples from children at 3
      years post-BCG vaccination were tested for cytokine/chemokine responses to M.
      tuberculosis antigens. Furthermore, the IFN-gamma responses to M. tuberculosis
      antigens were followed up for 40 children at 8 years post-BCG vaccination, and 15
      TB patients were recruited as a control group for the M. tuberculosis ESAT-6
      response in Malawi. IFN-gamma enzyme-linked immunosorbent assays (ELISAs) on
      supernatants from diluted whole-blood assays, IFN-gamma enzyme-linked
      immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and
      multiplex bead assays were performed. More than 45% of the responders to M.
      tuberculosis ESAT-6 showed IFN-gamma responses to M. avium and M. kansasii ESAT
      6. In response to M. tuberculosis ESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL
      13, and IL-17 differentiated the stronger IFN-gamma responders to M. tuberculosis
      ESAT-6 from those who preferentially responded to M. kansasii and M. avium ESAT
      6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified
      as a putative immunological biosignature to differentiate latent TB infection
      from exposure to M. avium and M. kansasii in Malawian children, indicating that
      this signature might be particularly informative in areas where both TB and
      exposure to environmental nontuberculous mycobacteria are endemic. 

PMID- 24285819
TI  - Oral immunization with recombinant Lactobacillus acidophilus expressing the
      adhesin Hp0410 of Helicobacter pylori induces mucosal and systemic immune
      responses.
AB  - Helicobacter pylori infection is relatively common worldwide and is closely
      related to gastric mucosa-associated lymphoid tissue (MALT) lymphoma, chronic
      gastritis, and stomach ulcers. Therefore, a safe and effective method for
      preventing H. pylori infection is urgently needed. Given that developing an
      effective vaccine against H. pylori is one of the best alternatives, H. pylori
      adhesin Hp0410 was expressed in the food-grade bacterium Lactobacillus
      acidophilus. The recombinant live bacterial vaccine was then used to orally
      vaccinate mice, and the immunoprotective effects of Hp0410-producing strains were
      investigated. H. pylori colonization in the stomach of mice immunized with the
      recombinant L. acidophilus was significantly reduced, in comparison with that in
      control groups. Furthermore, mucosal secretory IgA antibodies were elicited in
      the mucosal tissue of mice immunized with the recombinant bacteria, and specific
      anti-Hp0410 IgG responses were also detected in mouse serum. There was a
      significant increase in the level of protection against gastric Helicobacter
      infection following a challenge with H. pylori Sydney strain 1 (SS1). Our results
      collectively indicate that adhesin Hp0410 is a promising candidate vaccine
      antigen, and recombinant L. acidophilus expressing Hp0410 is likely to constitute
      an effective, low-cost, live bacterial vaccine against H. pylori. 

PMID- 24285822
TI  - Urinary bisphenol A concentrations are associated with abnormal liver function in
      the elderly: a repeated panel study.
AB  - BACKGROUND: Bisphenol A (4,40-isopropylidenediphenol, BPA) is known to adversely
      affect various organs. The liver is reported to be affected by BPA in animal
      studies. However, there are few studies in humans on the effects of BPA on the
      liver. Therefore, we evaluated the relationship between urinary BPA levels and
      liver function in elderly subjects using repeated measurements. METHODS: From
      2008 to 2010, a total of 560 elderly subjects residing in Seoul were each
      evaluated up to three times. At the first visit, demographic data, environmental
      exposure and lifestyle information were obtained from a systemised questionnaire.
      At each visit, blood and urine samples were collected and stored for analysis.
      Linear mixed and GLIMMIX model analyses were performed after adjusting for age,
      sex, Body Mass Index, alcohol consumption, urinary cotinine concentrations,
      exercise frequency, and low-density lipoprotein cholesterol level. RESULTS: The
      mean urinary BPA concentration was 1.13 MUg/g creatinine. Significant
      relationships were observed between urinary BPA and aspartate aminotransferase,
      alanine aminotransferase, and gamma-glutamyl transferase after adjusting for
      potential confounders (p<0.05). When subjects were grouped according to urinary
      BPA concentrations divided by the median value, higher urinary BPA concentrations
      were associated with increased abnormal liver function (OR 2.66; 95% CI 1.15 to
      5.90). CONCLUSIONS: Community-level exposure to BPA was associated with abnormal
      liver function in the elderly, indicating that more stringent control of BPA is
      necessary to protect susceptible populations.

PMID- 24285823
TI  - 'It is surely a great criticism of our profession...' The next 20 years of equity
      focused systematic reviews.

PMID- 24285824
TI  - Natural killer cells in female infertility and recurrent miscarriage: a
      systematic review and meta-analysis.
AB  - INTRODUCTION Embryo implantation is a complex process involving maternal hormonal
      changes, immune responses and maturational events in the embryo. A pregnancy
      could fail when these events are not synchronized. It is speculated that in
      women, an elevation of natural killer (NK) cells may have an effect on
      reproductive performance, and NK cell levels in blood are currently being used as
      a diagnostic test to guide the initiation of therapies in patients with
      infertility. METHODS We conducted a systematic review to evaluate the (i) levels
      of NK cells in blood and endometrium in infertile versus fertile women, (ii)
      association between NK cells and IVF outcome, (iii) levels of NK cells in blood
      and endometrium in women with recurrent miscarriage (RM) versus controls. The
      following electronic databases were searched: Medline, EMBASE, Cochrane Library,
      Web of Science and National Research Register. RESULTS A total of 22 studies were
      included. Meta-analysis of studies that evaluated peripheral and uterine NK (uNK)
      cell percentages in infertile versus fertile women showed no significant
      difference between the two groups [standardized mean difference (SMD) -0.33; 95%
      confidence intervals (CI) -1.06, 0.4; P = 0.37; SMD -1.82; 95% CI -4.80, 1.17; P
      = 0.23 respectively]. Pooling of studies that reported peripheral NK cells as
      numbers showed significantly higher NK cell numbers in infertile women compared
      with fertile controls (SMD 3.16; 95% CI 1.07, 5.24; P = 0.003). Meta-analysis of
      studies that evaluated the role of NK cells in IVF outcome showed no significant
      difference in live birth rates in women with elevated NK cells or NK cell
      activity compared with women without elevated peripheral NK cells or NK cell
      activity (NK activity assessed using a cytotoxicity assay) (relative risk 0.57;
      95% CI 0.06, 5.22; P = 0.62). Meta-analysis of studies that evaluated peripheral
      NK cell percentages in women with RM versus controls showed significantly higher
      NK cell percentages in women with RM (SMD 1.36; 95% CI 0.04, 2.69; P = 0.04).
      Meta-analysis of studies that evaluated peripheral NK cell numbers showed
      significantly higher NK cell numbers in women with RM compared with controls (SMD
      0.81; 95% CI 0.47, 1.16; P < 0.00001). Meta-analysis of studies that evaluated
      uNK cells showed no significant difference in women with RM compared with
      controls (SMD 0.40; 95% CI -1.24, 2.04; P = 0.63). CONCLUSIONS Further research
      is needed before NK cell assessment can be recommended as a diagnostic tool in
      the context of female infertility or RM. There is no clear explanation as to why
      the results differ when data for NK cells are expressed as numbers or a
      percentage. On the basis of current evidence, NK cell analysis and immune therapy
      should be offered only in the context of clinical research. 

PMID- 24285825
TI  - Berry ripening: recently heard through the grapevine.
AB  - Grapevine (Vitis vinifera L.) is a non-climacteric fruit species used as table
      fruit, dried raisins, and for vinification (wines) and distillation (liquors). In
      recent years, our knowledge of the molecular basis of ripening regulation has
      improved. Water status, light conditions, and temperature may hasten, delay, or
      enhance ripening. Hormones seem to play a central role, as their concentrations
      change prior to and during ripening and in response to several environmental
      cues. The review summarizes recent data related to the molecular and hormonal
      control of grape berry development and ripening, with special emphasis on
      secondary metabolism and its response to the environment, and pinpoints some
      experimental limitations. 

PMID- 24285826
TI  - Disruption of the microtubule network alters cellulose deposition and causes
      major changes in pectin distribution in the cell wall of the green alga, Penium
      margaritaceum.
AB  - Application of the dintroaniline compound, oryzalin, which inhibits microtubule
      formation, to the unicellular green alga Penium margaritaceum caused major
      perturbations to its cell morphology, such as swelling at the wall expansion zone
      in the central isthmus region. Cell wall structure was also notably altered,
      including a thinning of the inner cellulosic wall layer and a major disruption of
      the homogalacturonan (HG)-rich outer wall layer lattice. Polysaccharide
      microarray analysis indicated that the oryzalin treatment resulted in an increase
      in HG abundance in treated cells but a decrease in other cell wall components,
      specifically the pectin rhamnogalacturonan I (RG-I) and arabinogalactan proteins
      (AGPs). The ring of microtubules that characterizes the cortical area of the cell
      isthmus zone was significantly disrupted by oryzalin, as was the extensive
      peripheral network of actin microfilaments. It is proposed that the disruption of
      the microtubule network altered cellulose production, the main load-bearing
      component of the cell wall, which in turn affected the incorporation of HG in the
      two outer wall layers, suggesting coordinated mechanisms of wall polymer
      deposition. 

PMID- 24285827
TI  - Low-affinity IgM antibodies lacking somatic hypermutations are produced in the
      secondary response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl hapten.
AB  - Class-switched memory B cells, which are generated through the processes of
      somatic hypermutation (SHM) and affinity-based selection in germinal centers,
      contribute to the production of affinity-matured IgG antibodies in the secondary
      immune response. However, changes in the affinity of IgM antibodies during the
      immune response have not yet been studied, although IgM(+) memory B cells have
      been shown to be generated. In order to understand the relationship between IgM
      affinity and the recall immune response, we prepared hybridomas producing anti-(4
      hydroxy-3-nitrophenyl)acetyl (NP) IgM antibodies from C57BL/6 mice and from
      activation-induced cytidine deaminase (AID)-deficient mice. Binding analysis by
      ELISA showed that mAbs obtained from the secondary immune response contained IgM
      mAbs with affinity lower than the affinity of mAbs obtained from the primary
      response. By analyzing sequences of the IgM genes of hybridomas and plasma cells,
      we found many unmutated VH genes. VH genes that had neither tyrosine nor glycine
      at position 95 were frequent. The repertoire change may correlate with the lower
      affinity of IgM antibodies in the secondary response. The sequence and affinity
      changes in IgM antibodies were shown to be independent of SHM by analyzing
      hybridomas from AID-deficient mice. A functional assay revealed a reciprocal
      relationship between affinity and complement-dependent hemolytic activity toward
      NP-conjugated sheep RBCs; IgM antibodies with lower affinities had higher
      hemolytic activity. These findings indicate that lower affinity IgM antibodies
      with enhanced complement activation function are produced in the secondary immune
      response.

PMID- 24285829
TI  - The elephants of Gash-Barka, Eritrea: nuclear and mitochondrial genetic patterns.
AB  - Eritrea has one of the northernmost populations of African elephants. Only about
      100 elephants persist in the Gash-Barka administrative zone. Elephants in Eritrea
      have become completely isolated, with no gene flow from other elephant
      populations. The conservation of Eritrean elephants would benefit from an
      understanding of their genetic affinities to elephants elsewhere on the continent
      and the degree to which genetic variation persists in the population. Using dung
      samples from Eritrean elephants, we examined 18 species-diagnostic single
      nucleotide polymorphisms in 3 nuclear genes, sequences of mitochondrial HVR1 and
      ND5, and genotyped 11 microsatellite loci. The sampled Eritrean elephants carried
      nuclear and mitochondrial DNA markers establishing them as savanna elephants,
      with closer genetic affinity to Eastern than to North Central savanna elephant
      populations, and contrary to speculation by some scholars that forest elephants
      were found in Eritrea. Mitochondrial DNA diversity was relatively low, with 2
      haplotypes unique to Eritrea predominating. Microsatellite genotypes could only
      be determined for a small number of elephants but suggested that the population
      suffers from low genetic diversity. Conservation efforts should aim to protect
      Eritrean elephants and their habitat in the short run, with restoration of
      habitat connectivity and genetic diversity as long-term goals. 

PMID- 24285830
TI  - Characterization of multilayered and composite edible films from chitosan and
      beeswax.
AB  - Chitosan-based edible films were prepared and subjected to cross-linking
      reactions using sodium tripolyphosphate and/or to beeswax coating on both films
      interfaces. In addition, chitosan-beeswax emulsion-based films were produced. The
      goal of these modifications of the chitosan films was the improvement of their
      barrier to water vapor and to decrease their affinity to liquid water maintaining
      or improving the mechanical and optical properties of the original chitosan
      films. The cross-linking with tripolyphosphate decreased both the water vapor
      permeability and the water absorption capacity to about 55% and 50% of that of
      the original chitosan films, respectively. However, there was an increase in the
      films stiffness, revealed by the increased Young modulus from 42 kPa up to 336
      kPa. The multilayered wax-chitosan-wax films exhibited a similar improvement of
      the barrier properties to water vapor, with the advantage of maintaining the
      mechanical properties of the original chitosan films. However, these wax-coated
      films showed a higher water absorption capacity, which is believed to be a
      consequence of water entry into small pores between the film and the wax layers.
      Regarding the film samples subjected to cross-linking and further coating with
      beeswax, a similar behavior as the uncoated cross-linked films was observed. The
      emulsion-based composite films were characterized by a substantial decrease of
      the water vapor permeability (40%), along with a decrease in their stiffness.
      Regarding the optical properties, all films presented a yellowish color with
      similar values of lightness, chroma, and hue.

PMID- 24285831
TI  - Effect of phage and host concentration on the inactivation of Escherichia coli
      O157:H7 on cooked and raw beef.
AB  - A previously described phage infecting Escherichia coli O157:H7 was added to raw
      and cooked beef pieces at concentrations ranging from 10(1)-10(8) plaque forming
      units/cm(2) to either low (<100 CFU/cm(2)) or high (10(4) CFU/cm(2))
      concentrations of host bacterial cells. Incubation for up to 24 h was performed
      at 5 C and 24 C to simulate refrigerated and room temperature storage/temperature
      abuse. Surviving bacteria were enumerated during the incubation period, with
      phages being counted at the first and last sampling times. Significant reductions
      of E. coli O157:H7 of the order of >4 log10 CFU/cm(2) at both temperatures could
      be achieved compared to phage-free controls. There was a trend for greater
      inactivation to occur with increasing phage concentration. While re-growth of
      surviving cells occurred in nearly all samples incubated for 24 h at 24 C, these
      conditions are not typical of those experienced by perishable foods. It was
      concluded that phages can be used to reduce the concentration of a bacterial
      pathogen on meat, but the concentration of phages needs to be high (>4-5 log10
      plaque forming units/cm(2)) for reductions to occur. A concentration of the order
      8 log10 plaque forming units/cm(2) was needed to achieve a 4 log10 CFU/cm(2)
      reduction.

PMID- 24285828
TI  - Controlling immune responses by targeting antigens to dendritic cell subsets and
      B cells.
AB  - Delivering antigens in vivo by coupling them to mAbs specific for unique
      receptors on antigen-presenting cells (APCs) is a promising approach for
      modulating immune responses. Antigen delivery to receptors found on myeloid
      dendritic cell (DC) subsets, plasmacytoid DCs and B cells has shown them all to
      be viable targets to stimulate either the cellular or humoral arms of the immune
      system. It is now evident that antigen-targeting approaches can also be used to
      invoke antigen-specific inhibition of immune responses. The outcome of activation
      versus inhibition is determined by a combination of factors that include the
      choice of APC, the receptor that is targeted, whether to include an adjuvant and,
      if so, which adjuvant to employ. In addition to their use as a means to modulate
      immune responses, antigen-targeting systems are also a useful method to
      investigate the function of DC subsets and the early mechanistic events that
      underlie the initiation of both cellular and humoral immune responses. In this
      review, we focus on the literature surrounding the control of B-cell responses
      when antigen is delivered to various APC subsets. 

PMID- 24285832
TI  - Barred from each other: why normative husbands remain married to incarcerated
      wives--an exploratory study.
AB  - This study explores men's motivation and justification to remain married to their
      criminal, imprisoned wives. Using semistructured interviews and content-analysis,
      data were collected and analyzed from eight men who maintain stable marriage
      relationships with their incarcerated wives. Participants are normative men who
      describe incarceration as a challenge that enhances mutual responsibility and
      commitment. They exaggerate the extent to which their partners resemble
      archetypal romantic ideals. They use motivational accounts to explain the woman's
      criminal conduct, which is perceived as nonrelevant to her real identity.
      Physical separation and lack of physical intimacy are perceived as the major
      difficulties in maintaining their marriage relations. Length of imprisonment and
      marriage was found to be related to the decision whether to continue or terminate
      the relationships. Women-inmates' partners experience difficulties and use coping
      strategies very similar to those cited by other normative spouses facing lengthy
      separation. 

PMID- 24285833
TI  - Trying to restore justice: bureaucracies, risk management, and disciplinary
      boundaries in New Zealand criminal justice.
AB  - New Zealand is well known for its restorative justice conferences in the youth
      justice system. However, restorative justice has yet to overwhelm the adult
      criminal justice system. Based on interviews in New Zealand with correctional
      staff, restorative justice providers, and others, this article explores the
      reason for the modest inroads that restorative practice has made, and suggests
      that the general context may explain the limits of restorative justice in other
      places. The article argues that bureaucratic silos make it challenging to
      determine if restorative practice might fit within a rehabilitation or
      reintegration framework. In addition, because of the dominance of psychological
      modes for assessing and treating criminal behavior, an overarching preoccupation
      with risk management orients correctional practice toward treatment. Moreover,
      restorative justice's affiliation with victims' perspectives has made its
      placement within offender reintegration difficult to imagine. Finally, the penal
      populism that frames correctional practice in New Zealand, and other Anglophone
      countries, makes alternative to punishment harder to sell. However, the current
      liminal state of correctional practice creates an opportunity to conceive of more
      humanistic ways of repairing the harm caused by crime. 

PMID- 24285834
TI  - Dual Diagnosis in Prisoners: Childhood Sexual and Physical Abuse as Predictors in
      Men and Women.
AB  - The study aims to determine the rate of dual diagnosis (DD), examine the most
      common mental disorders, and determine whether a history of childhood
      sexual/physical abuse (CSA/CPA) is associated with this phenomenon. One-hundred
      and eighty inmates from a Spanish prison were assessed using the Mini
      International Neuropsychiatric Interview and the Addiction Severity Index-6. The
      data showed that 46.8% of the males and 65.1% of the females had a substance use
      disorder. With regard to CPA, similar percentages were found in both genders.
      Nevertheless, rates of CSA were highest in females. Logistic regression analysis
      was performed by gender. CPA was predictor of DD for males, and CSA was predictor
      of DD for females, showing the greatest weight. In addition, in both cases, the
      number of drugs of abuse was an adequate predictor. We can state that these forms
      of maltreatment are risk factors for the development of a broad range of
      psychopathological problems.

PMID- 24285835
TI  - Altered IFN-gamma-mediated immunity and transcriptional expression patterns in N
      Ethyl-N-nitrosourea-induced STAT4 mutants confer susceptibility to acute typhoid
      like disease.
AB  - Salmonella enterica is a ubiquitous Gram-negative intracellular bacterium that
      continues to pose a global challenge to human health. The etiology of Salmonella
      pathogenesis is complex and controlled by pathogen, environmental, and host
      genetic factors. In fact, patients immunodeficient in genes in the IL-12, IL
      23/IFN-gamma pathway are predisposed to invasive nontyphoidal Salmonella
      infection. Using a forward genomics approach by N-ethyl-N-nitrosourea (ENU)
      germline mutagenesis in mice, we identified the Ity14 (Immunity to Typhimurium
      locus 14) pedigree exhibiting increased susceptibility following in vivo
      Salmonella challenge. A DNA-binding domain mutation (p.G418_E445) in Stat4
      (Signal Transducer and Activator of Transcription Factor 4) was the causative
      mutation. STAT4 signals downstream of IL-12 to mediate transcriptional regulation
      of inflammatory immune responses. In mutant Ity14 mice, the increased splenic and
      hepatic bacterial load resulted from an intrinsic defect in innate cell function,
      IFN-gamma-mediated immunity, and disorganized granuloma formation. We further
      show that NK and NKT cells play an important role in mediating control of
      Salmonella in Stat4(Ity14/Ity14) mice. Stat4(Ity14/Ity14) mice had increased
      expression of genes involved in cell-cell interactions and communication, as well
      as increased CD11b expression on a subset of splenic myeloid dendritic cells,
      resulting in compromised recruitment of inflammatory cells to the spleen during
      Salmonella infection. Stat4(Ity14/Ity14) presented upregulated compensatory
      mechanisms, although inefficient and ultimately Stat4(Ity14/Ity14) mice develop
      fatal bacteremia. The following study further elucidates the pathophysiological
      impact of STAT4 during Salmonella infection. 

PMID- 24285836
TI  - Macrophages are more potent immune suppressors ex vivo than immature myeloid
      derived suppressor cells induced by metastatic murine mammary carcinomas.
AB  - Myeloid-derived suppressor cells (MDSCs) are emerging as potential promoters of
      metastatic tumor growth, and there is interest in targeting immature MDSCs by
      inducing their differentiation into more mature myeloid cells. We used all-trans
      retinoic acid (ATRA) to differentiate MDSCs in mice bearing metastatic 4T1 or
      4TO7 murine mammary tumors, and assessed the immune-suppressive mechanisms and
      potencies of different myeloid cell subpopulations. Metastatic mammary tumors
      induced the accumulation of distinct populations of immature CD11b(+)Gr1(+)F4/80(
      )Ly6C(mid)Ly6G(+) MDSCs ("Gr1(+) cells") and mature CD11b(+)Gr1(-)F4/80(+) cells
      ("F4/80(+) cells") in metastatic target organs. ATRA triggered the
      differentiation of Gr1(+) cells into F4/80(+) cells in the lungs and,
      unexpectedly, enhanced pulmonary metastatic tumor growth. We found that
      F4/80(+)Ly6C(-)Ly6G(-) mature macrophages (Ms) were up to 30-fold more potent
      immune suppressors than Gr1(+) cells on a per-cell basis, which we postulate may
      contribute to the increased metastatic growth observed with ATRA treatment.
      F4/80(+) cells and Gr1(+) cells used different reactive oxygen species (ROS)
      mediated mechanisms of immunosuppression ex vivo, with F4/80(+) cells producing
      higher levels of ROS, which is consistent with their superior immunosuppressive
      abilities. These data highlight the potent immunosuppressive functions of Ms,
      reveal that Ms can suppress T cell responses via ROS production, and suggest that
      ROS inhibitors may be useful in promoting antitumor immune responses. Our
      findings also caution against using ATRA to modulate myeloid cell differentiation
      and function to treat breast cancer metastases in the lung, and support the
      development of therapeutic strategies to enhance antitumor immunity by targeting
      myeloid cells as a collective group. 

PMID- 24285837
TI  - Targeting CD137 enhances vaccine-elicited anti-respiratory syncytial virus CD8+ T
      cell responses in aged mice.
AB  - Respiratory syncytial virus (RSV) causes significant morbidity and mortality in
      children and the elderly. No vaccines for RSV are in use. Because of
      immunosenescence, the immunologic requirements for a successful RSV vaccine in
      the elderly might differ from a RSV vaccine for young children. Using an aged
      mouse model of RSV pathogenesis, we found that aged mice had impaired Ag-specific
      CD8(+) T cell responses and delayed RSV clearance compared with young mice. To
      study vaccine-elicited RSV-specific CD8(+) T cells in aged mice, we used a
      peptide vaccine approach. TriVax is a commixture of a peptide representing
      immunodominant RSV CD8(+) T cell epitope M282-90, a TLR agonist (polyinosinic
      polycytidylic acid), and a costimulatory anti-CD40 Ab. TriVax vaccination
      generated robust, polyfunctional, and protective CD8(+) T cell responses in young
      BALB/c mice, but not in 18-mo-old (aged) BALB/c mice. We hypothesized that
      treatment of aged mice with agonistic anti-CD137 (41BB) mAb will partially
      restore T cell responses and TriVax efficacy in aged mice. We immunized 18-mo-old
      BALB/c mice twice with TriVax + anti-41BB mAb or TriVax + isotype control Ab.
      Coadministration of anti-41BB mAb with TriVax enhanced RSV-specific CD8(+) T cell
      responses and TriVax efficacy in challenge experiments. Triggering the 41BB
      costimulatory pathway may be a strategy for enhancing T cell responses to
      vaccines in the elderly. 

PMID- 24285838
TI  - IL-6-mediated induction of matrix metalloproteinase-9 is modulated by JAK
      dependent IL-10 expression in macrophages.
AB  - The mechanisms by which IL-6 contributes to the pathogenesis of chronic
      inflammatory diseases and cancer are not fully understood. We previously reported
      that cyclooxygenase-2 (Cox-2)-dependent PGE2 synthesis regulates macrophage
      matrix metalloproteinase (MMP)-9 expression, an endopeptidase that participates
      in diverse pathologic processes. In these studies, we determined whether IL-6
      regulates the Cox-2->PGE2->MMP-9 pathway in murine macrophages. IL-6 coinduced
      Cox-2 and microsomal PGE synthase-1, and inhibited the expression of 15
      hydroxyprostaglandin dehydrogenase, leading to increased levels of PGE2. In
      addition, IL-6 induced MMP-9 expression, suggesting that the observed proteinase
      expression was regulated by the synthesis of PGE2. However, inhibition of PGE2
      synthesis partially suppressed IL-6-mediated induction of MMP-9. In the canonical
      model of IL-6-induced signaling, JAK activation triggers STAT and MAPK(erk1/2)
      signaling pathways. Therefore, the ability of structurally diverse JAK inhibitors
      to block IL-6-induced MMP-9 expression was examined. Inhibition of JAK blocked IL
      6-induced phosphorylation of STAT3, but failed to block the phosphorylation of
      MAPK(erk1/2), and unexpectedly enhanced MMP-9 expression. In contrast, MEK-1
      inhibition blocked IL-6-induced phosphorylation of MAPK(erk1/2) and MMP-9
      expression without affecting the phosphorylation of STAT3. Thus, IL-6-induced MMP
      9 expression is dependent on the activation of MAPK(erk1/2) and is restrained by
      a JAK-dependent gene product. Using pharmacologic and genetic approaches, we
      identified JAK-dependent induction of IL-10 as a potent feedback mechanism
      controlling IL-6-induced MMP-9 expression. Together, these data reveal that IL-6
      induces MMP-9 expression in macrophages via Cox-2-dependent and -independent
      mechanisms, and identifies a potential mechanism linking IL-6 to the pathogenesis
      of chronic inflammatory diseases and cancer. 

PMID- 24285839
TI  - Cutting edge: Expression of FcgammaRIIB tempers memory CD8 T cell function in
      vivo.
AB  - During reinfection, high-affinity IgG Abs form complexes with both soluble Ag and
      Ag displayed on the surface of infected cells. These interactions regulate
      cellular activation of both innate cells and B cells, which express specific
      combinations of activating FcgammaRs (FcgammaRI, FcgammaRIII, FcgammaRIV) and/or
      the inhibitory FcgammaR (FcgammaRIIB). Direct proof for functional expression of
      FcgammaR by Ag-specific CD8 T cells is lacking. In this article, we show that the
      majority of memory CD8 T cells generated by bacterial or viral infection express
      only FcgammaRIIB, and that FcgammaRIIB could be detected on previously activated
      human CD8 T cells. Of note, FcgammaR stimulation during in vivo Ag challenge not
      only inhibited the cytotoxicity of memory CD8 T cells against peptide-loaded or
      virus-infected targets, but FcgammaRIIB blockade during homologous virus
      challenge enhanced the secondary CD8 T cell response. Thus, memory CD8 T cells
      intrinsically express a functional FcgammaRIIB, permitting Ag-Ab complexes to
      regulate secondary CD8 T cell responses. 

PMID- 24285840
TI  - Increased rate of phenocopies in all age groups in BRCA1/BRCA2 mutation kindred,
      but increased prospective breast cancer risk is confined to BRCA2 mutation
      carriers.
AB  - BACKGROUND: To establish, if among unaffected noncarrier relatives in a family
      with an established BRCA1/2 mutation, there is an increased risk of breast
      cancer. METHODS: We identified 49 women with breast cancer who were first-degree
      relatives of a pathogenic mutation carrier among 807 BRCA1/2 families but who
      tested negative for the specific mutation. A prospective analysis of breast
      cancer from date of family ascertainment was performed for first-degree relatives
      of proven BRCA1/2 mutation carriers and compared with population-expected
      incidence rates. RESULTS: Women who prospectively test negative for BRCA1/2
      mutations showed excess risk of breast cancer to be confined to BRCA2 noncarriers
      with an observed:expected (O/E) ratio of 4.57 [95% confidence interval (CI) 2.50
      7.67; P < 0.0001; O/E in BRCA1 noncarriers, 1.77]; this dropped to 2.01 for BRCA2
      [relative risk (RR), 1.99; 95% CI, 0.54-5.10] from date of predictive test.
      Genotyping of 18 breast cancer susceptibility single-nucleotide polymorphisms
      (SNP) defined an RR of 1.31 for BRCA2 breast cancer phenocopies with a breast
      cancer diagnosis at age less than 60 years. CONCLUSION: Noncarriers remain at
      risk in the prospective follow-up of women who tested negative for BRCA1/2. Women
      testing negative in BRCA2 families may have increased risk of breast cancer
      compared with population levels, particularly with strong breast cancer history
      in close relatives. Any increased risk in BRCA1 families is likely to be
      insufficient to recommend additional interventions. IMPACT: Our work can help
      with counseling women from BRCA1/2 families who have tested negative, and could
      impact on how individual breast cancer risk is related back to these women.

PMID- 24285841
TI  - Helicobacter pylori and colorectal cancer risk--letter.

PMID- 24285842
TI  - Helicobacter pylori Biomarkers and Risk of Colorectal Oncogenesis--Response.

PMID- 24285843
TI  - Alternating zones selective to faces and written words in the human ventral
      occipitotemporal cortex.
AB  - Recognition of faces and written words is associated with category-specific brain
      activation in the ventral occipitotemporal cortex (vOT). However, topological and
      functional relationships between face-selective and word-selective vOT regions
      remain unclear. In this study, we collected data from patients with intractable
      epilepsy who underwent high-density recording of surface field potentials in the
      vOT. "Faces" and "letterstrings" induced outstanding category-selective responses
      among the 24 visual categories tested, particularly in high-gamma band powers.
      Strikingly, within-hemispheric analysis revealed alternation of face-selective
      and letterstring-selective zones within the vOT. Two distinct face-selective
      zones located anterior and posterior portions of the mid-fusiform sulcus whereas
      letterstring-selective zones alternated between and outside of these 2 face
      selective zones. Further, a classification analysis indicated that activity
      patterns of these zones mostly represent dedicated categories. Functional
      connectivity analysis using Granger causality indicated asymmetrically directed
      causal influences from face-selective to letterstring-selective regions. These
      results challenge the prevailing view that different categories are represented
      in distinct contiguous regions in the vOT. 

PMID- 24285844
TI  - Correlate of immune protection against HSV-1 genital disease in vaccinated women.
AB  - BACKGROUND: Previously we conducted a double-blind controlled, randomized
      efficacy field trial of gD-2 HSV vaccine adjuvanted with ASO4 in 8323 women.
      Subjects had been previously selected to be seronegative for HSV-1 and HSV-2. We
      found that vaccine was 82% protective against HSV-1 genital disease, but offered
      no significant protection against HSV-2 genital disease. METHODS: To better
      understand the results of the efficacy study, post-vaccination anti-gD-2 antibody
      concentrations from all HSV infected subjects and matched uninfected controls
      were measured. Three models were used to determine whether thes responses
      correlated with protection against HSV infection or disease. Similarly, cellular
      immune responses from a subset of subjects and matched controls were evaluated
      for a correlation with HSV protection. RESULTS: Antibodies to gD-2 correlated
      with protection against HSV-1 infection with higher antibody concentration
      associated with higher efficacy. Cellular immune responses to gD-2 did not
      correlate with protection. CONCLUSIONS: The protection against HSV-1 infection
      observed in the Herpevac Trial for Women was associated with antibodies directed
      against the vaccine. Clinical Trials Registration NCT00057330.

PMID- 24285845
TI  - The contribution of suilysin to the pathogenesis of Streptococcus suis
      meningitis.
AB  - BACKGROUND: Streptococcus suis is an emerging zoonotic pathogen, and causes
      sepsis and meningitis in humans. Although sequence type (ST) 1 and ST104 strains
      are capable of causing sepsis, ST1 strains commonly cause meningitis. In this
      study, we investigated the role of suilysin, a member of cholesterol-dependent
      cytolysins, in differential pathogenicity between ST1 and ST104 strains. METHODS:
      The levels of transcription and translation of the sly gene and messenger RNA of
      both ST strains were compared by means of quantitative polymerase chain reaction
      and Western blotting. Survival rates and bacterial densities in brain were
      compared between mice infected with wild-type and sly-knockout ST1 strain. ST104
      infections with or without complementation of suilysin were also assessed.
      RESULTS: The amounts of suilysin produced by ST1 strains were much higher than
      those produced by ST104 strains. Lower production of suilysin by ST104 strains
      were attributed to the attenuated sly gene expression, which seemed to be
      associated with 2 nucleotide insertions in sly promoter region. Furthermore,
      suilysin contributed to the higher bacterial density and enhanced inflammation in
      brain and increased mortality. CONCLUSIONS: Our data may explain why ST1 strains,
      but not ST104 strains, commonly cause meningitis and also suggest the
      contribution of suilysin to the pathogenesis of meningitis in humans.

PMID- 24285846
TI  - The influence of behaviors and relationships on the vaginal microbiota of women
      and their female partners: the WOW Health Study.
AB  - BACKGROUND: A community-based study of women who have sex with women (WSW) was
      performed to determine the burden of bacterial vaginosis (BV), and behavioral
      factors influencing the vaginal microbiota of women and their female sexual
      partners (FSPs), as measured by Nugent score (NS). METHODS: In a cross-sectional
      study of 18-55-year-old WSW recruited nationally, participants completed
      questionnaires and self-collected vaginal swab samples weekly on 3 occasions. BV
      was defined as an NS of 7-10. Factors associated with BV, stability of NS
      category, and concordance of these categories in co-enrolled couples were
      examined with multivariable logistic regression analysis. RESULTS: A total of 458
      participants were recruited; 192 were co-enrolled with their FSP (96 couples). BV
      was detected in 125 women (27%; 95% confidence interval [CI], 23%-32%). BV was
      associated with >=4 lifetime FSPs (adjusted odds ratio [AOR], 1.9; 95% CI, 1.2
      3.1), an FSP with BV symptoms (AOR, 2.9; 1.0-8.2) and smoking, with >=30
      cigarettes per week showing greatest odds (AOR, 2.7; 1.5-5.0). Of 428 women
      returning >=2 swab samples, 375 (88%) had a stable NS category across all
      samples, predominantly reflecting normal flora. Co-enrolled WSW were less likely
      to have BV (31% vs 23%; P = .07), and the majority (70%) were concordant for NS
      category (kappa = 0.47; P <= .01), with most concordant for normal flora.
      Concordant NS category was associated with a relationship of >6 months (AOR, 4.7;
      95% CI, 1.4-16.4) and frequent sexual contact (more than once per month; AOR,
      2.7; 1.0-7.1). CONCLUSIONS: BV is associated with key behaviors and smoking
      practices in WSW, but longer-duration, sexually active WSW partnerships support a
      stable favorable vaginal microbiota.

PMID- 24285847
TI  - A paradigm shift: vaccine-induced antibodies as an immune correlate of protection
      against herpes simplex virus type 1 genital herpes.

PMID- 24285849
TI  - A modern ampelography: a genetic basis for leaf shape and venation patterning in
      grape.
AB  - Terroir, the unique interaction between genotype, environment, and culture, is
      highly refined in domesticated grape (Vitis vinifera). Toward cultivating
      terroir, the science of ampelography tried to distinguish thousands of grape
      cultivars without the aid of genetics. This led to sophisticated phenotypic
      analyses of natural variation in grape leaves, which within a palmate-lobed
      framework exhibit diverse patterns of blade outgrowth, hirsuteness, and venation
      patterning. Here, we provide a morphometric analysis of more than 1,200 grape
      accessions. Elliptical Fourier descriptors provide a global analysis of leaf
      outlines and lobe positioning, while a Procrustes analysis quantitatively
      describes venation patterning. Correlation with previous ampelography suggests an
      important genetic component, which we confirm with estimates of heritability. We
      further use RNA-Seq of mutant varieties and perform a genome-wide association
      study to explore the genetic basis of leaf shape. Meta-analysis reveals a
      relationship between leaf morphology and hirsuteness, traits known to correlate
      with climate in the fossil record and extant species. Together, our data
      demonstrate a genetic basis for the intricate diversity present in grape leaves.
      We discuss the possibility of using grape leaves as a breeding target to preserve
      terroir in the face of anticipated climate change, a major problem facing
      viticulture. 

PMID- 24285848
TI  - Antiretroviral therapy reduces the rate of hepatic decompensation among HIV- and
      hepatitis C virus-coinfected veterans.
AB  - BACKGROUND:  Human immunodeficiency virus (HIV) coinfection accelerates the rate
      of liver disease outcomes in individuals chronically infected with hepatitis C
      virus (HCV). It remains unclear to what degree combination antiretroviral therapy
      (ART) protects against HCV-associated liver failure. METHODS:  We evaluated 10
      090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort,
      who had not initiated ART at entry, for incident hepatic decompensation between
      1996 and 2010. We defined ART initiation as the first pharmacy fill date of a
      qualifying ART regimen of >=3 drugs from >=2 classes. Hepatic decompensation was
      defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient
      diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal
      hemorrhage. To account for potential confounding by indication, marginal
      structural models were used to estimate hazard ratios (HRs) of hepatic
      decompensation, comparing initiation of ART to noninitiation. RESULTS:  We
      observed 645 hepatic decompensation events in 46 444 person-years of follow-up
      (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had
      a significantly reduced rate of hepatic decompensation relative to noninitiators
      (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals
      with HIV RNA <=400 copies/mL at baseline from the analysis (assuming that they
      may have received undocumented ART at entry), the hazard ratio became more
      pronounced (HR = 0.59; 95% CI, .43-.82). CONCLUSIONS:  Initiation of ART
      significantly reduced the rate of hepatic decompensation by 28%-41% on average.
      These results suggest that ART should be administered to HIV/HCV-coinfected
      patients to lower the risk of end-stage liver disease.

PMID- 24285853
TI  - Intestinal-type adenocarcinoma possibly arising from a remnant of the
      rectovaginal fistula tract formed after intermediate-level imperforate anus
      repair.

PMID- 24285851
TI  - Molecular mechanism of microRNA396 mediating pistil development in Arabidopsis.
AB  - The precise control of gene regulation, and hence, correct spatiotemporal tissue
      patterning, is crucial for plant development. Plant microRNAs can constrain the
      expression of their target genes at posttranscriptional levels. Recently,
      microRNA396 (miR396) has been characterized to regulate leaf development by
      mediating cleavage of its GROWTH-REGULATING FACTOR (GRF) targets. miR396 is also
      preferentially expressed in flowers. However, its function in flower development
      is unclear. In addition to narrow leaves, pistils with a single carpel were also
      observed in miR396 overexpression plants. The dramatically reduced expression
      levels of miR396 targets (GRF1, GRF2, GRF3, GRF4, GRF7, GRF8, and GRF9) caused
      pistil abnormalities, because the miR396-resistant version of GRF was able to
      rescue miR396-overexpressing plants. Both GRF and GRF-INTERACTING FACTOR (GIF)
      genes are highly expressed in developing pistils, and their expression patterns
      are negatively correlated with that of miR396. GRF interacted with GIF to form
      the GRF/GIF complex in plant cell nucleus. miR396 suppressed the expression of
      GRF genes, resulting in reduction of GRF/GIF complex. gif single mutant displayed
      normal pistils, whereas gif triple mutant gif1/gif2/gif3 produced abnormal
      pistils, which was a phenocopy of 35S:MIR396a/grf5 plants. GRF and GIF function
      as cotranscription factors, and both are required for pistil development. Our
      analyses reveal an important role for miR396 in controlling carpel number and
      pistil development via regulation of the GRF/GIF complex. 

PMID- 24285850
TI  - Reciprocal responses in the interaction between Arabidopsis and the cell-content
      feeding chelicerate herbivore spider mite.
AB  - Most molecular-genetic studies of plant defense responses to arthropod herbivores
      have focused on insects. However, plant-feeding mites are also pests of diverse
      plants, and mites induce different patterns of damage to plant tissues than do
      well-studied insects (e.g. lepidopteran larvae or aphids). The two-spotted spider
      mite (Tetranychus urticae) is among the most significant mite pests in
      agriculture, feeding on a staggering number of plant hosts. To understand the
      interactions between spider mite and a plant at the molecular level, we examined
      reciprocal genome-wide responses of mites and its host Arabidopsis (Arabidopsis
      thaliana). Despite differences in feeding guilds, we found that transcriptional
      responses of Arabidopsis to mite herbivory resembled those observed for
      lepidopteran herbivores. Mutant analysis of induced plant defense pathways showed
      functionally that only a subset of induced programs, including jasmonic acid
      signaling and biosynthesis of indole glucosinolates, are central to Arabidopsis's
      defense to mite herbivory. On the herbivore side, indole glucosinolates
      dramatically increased mite mortality and development times. We identified an
      indole glucosinolate dose-dependent increase in the number of differentially
      expressed mite genes belonging to pathways associated with detoxification of
      xenobiotics. This demonstrates that spider mite is sensitive to Arabidopsis
      defenses that have also been associated with the deterrence of insect herbivores
      that are very distantly related to chelicerates. Our findings provide molecular
      insights into the nature of, and response to, herbivory for a representative of a
      major class of arthropod herbivores. 

PMID- 24285854
TI  - Five-year relative survival rate of lung cancer in the USA, Europe and Japan.

PMID- 24285852
TI  - An RNA sequencing transcriptome analysis reveals novel insights into molecular
      aspects of the nitrate impact on the nodule activity of Medicago truncatula.
AB  - The mechanism through which nitrate reduces the activity of legume nodules is
      controversial. The objective of the study was to follow Medicago truncatula
      nodule activity after nitrate provision continuously and to identify molecular
      mechanisms, which down-regulate the activity of the nodules. Nodule H2 evolution
      started to decline after about 4 h of nitrate application. At that point in time,
      a strong shift in nodule gene expression (RNA sequencing) had occurred (1,120
      differentially expressed genes). The most pronounced effect was the down
      regulation of 127 genes for nodule-specific cysteine-rich peptides. Various other
      nodulins were also strongly down-regulated, in particular all the genes for
      leghemoglobins. In addition, shifts in the expression of genes involved in
      cellular iron allocation and mitochondrial ATP synthesis were observed.
      Furthermore, the expression of numerous genes for the formation of proteins and
      glycoproteins with no obvious function in nodules (e.g. germins, patatin, and
      thaumatin) was strongly increased. This occurred in conjunction with an up
      regulation of genes for proteinase inhibitors, in particular those containing the
      Kunitz domain. The additionally formed proteins might possibly be involved in
      reducing nodule oxygen permeability. Between 4 and 28 h of nitrate exposure, a
      further reduction in nodule activity occurred, and the number of differentially
      expressed genes almost tripled. In particular, there was a differential
      expression of genes connected with emerging senescence. It is concluded that
      nitrate exerts rapid and manifold effects on nitrogenase activity. A certain
      degree of nitrate tolerance might be achieved when the down-regulatory effect on
      late nodulins can be alleviated. 

PMID- 24285858
TI  - Breast and ovarian cancer risks in a large series of clinically ascertained
      families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations.
AB  - BACKGROUND: BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian
      cancer, but risks have been found to vary across studies and populations.
      METHODS: We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and
      studied the variation in breast and ovarian cancer risks using a modified
      segregation analysis model. RESULTS: The average cumulative breast cancer risk by
      age 70 years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI
      14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for
      ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for
      BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR)
      increased with more recent birth cohort (p heterogeneity = 0.0006) and stronger
      family histories of breast cancer (p heterogeneity < 0.001). For BRCA1, our data
      suggest a significant association between the location of the mutation and the
      ratio of breast to ovarian cancer (p<0.001). By contrast, in BRCA2 families, no
      evidence was found for risk heterogeneity by birth cohort, family history or
      mutation location. CONCLUSIONS: BRCA1 mutation carriers conferred lower overall
      breast and ovarian cancer risks than reported so far, while the estimates of
      BRCA2 mutations were among the lowest. The low estimates for BRCA1 might be due
      to older birth cohorts, a moderate family history, or founder mutations located
      within specific regions of the gene. These results are important for a more
      accurate counselling of BRCA1/2 mutation carriers.

PMID- 24285859
TI  - The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to
      a beta cell phenotype.
AB  - BACKGROUND: Mutation specific effects in monogenic disorders are rare. We
      describe atypical Fanconi syndrome caused by a specific heterozygous mutation in
      HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal
      hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant
      idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no
      genetic cause has been defined. METHODS AND RESULTS: We report six patients
      heterozygous for the p.R76W HNF4A mutation who have Fanconi syndrome and
      nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia. All six
      displayed a novel phenotype of proximal tubulopathy, characterised by generalised
      aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia
      and hypouricaemia, and additional features not seen in Fanconi syndrome:
      nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcaemia,
      and hypermagnesaemia. This was mutation specific, with the renal phenotype not
      being seen in patients with other HNF4A mutations. In silico modelling shows the
      R76 residue is directly involved in DNA binding and the R76W mutation reduces DNA
      binding affinity. The target(s) selectively affected by altered DNA binding of
      R76W that results in Fanconi syndrome is not known. CONCLUSIONS: The HNF4A R76W
      mutation is an unusual example of a mutation specific phenotype, with autosomal
      dominant atypical Fanconi syndrome in addition to the established beta cell
      phenotype.

PMID- 24285860
TI  - Correlation between FMR1 expression and clinical phenotype in discordant
      dichorionic-diamniotic monozygotic twin sisters with the fragile X mutation.
AB  - BACKGROUND: The clinical phenotypes of females with fragile X full mutations vary
      drastically. Comparisons of discordant monozygotic twins provide opportunities to
      ascertain crucial factors that influence disease phenotype penetrance. OBJECTIVE:
      To identify crucial factors influencing the phenotypic expression of fragile X
      syndrome (FXS). METHODS AND RESULTS: We describe a pair of discordant monozygotic
      female twins (dichorionic-diamniotic, Di-Di) with full mutation. The degrees of
      their phenotypic discordance regarding physical, psychiatric and behavioural
      features were quantified in a series of neuropsychological tests that varied
      significantly. Their FMR1 expression levels and whole genome DNA methylation
      profiling in blood were similar. Their similar life experiences also suggested
      that environmental factors had limited influence. However, the skewed
      inactivation of the normal X chromosome in the hair roots of twin A, resulting in
      large reduction in FMR1 expression compared to that of twin B, could adequately
      explain their widely variable phenotypes. CONCLUSIONS: The sixfold variation in
      hair root FMR1 expression, which reflected FMRP (fragile X mental retardation
      protein) expression in the brain, accounted for the disparate phenotypes in IQ,
      cognition, and social capability between the twins. Additionally, considering the
      Di-Di type twinning and different CGG repeat sizes, CGG expansion should occur
      before splitting at day 3 of gestation.

PMID- 24285861
TI  - Angular distribution of cross-sectioned cell boundaries at the distal terminal
      web in differentiating preameloblasts, inner enamel secretory ameloblasts and
      outer enamel secretory ameloblasts.
AB  - The cross-sectioned profiles of differentiating preameloblasts, inner enamel
      secretory ameloblasts and outer enamel secretory ameloblasts at the distal
      terminal web were quantitatively compared. First, the angles of each line
      constituting the sectioned cell polygons were measured, and the patterns of
      angular distribution histograms were compared. Second, all groups of line angles
      from one differentiating preameloblast population, two inner enamel secretory
      ameloblast and one outer enamel secretory ameloblast populations at the distal
      terminal web were compared statistically by the chi(2)-test using the multiple
      comparison method. The results showed that cell shapes between differentiating
      preameloblasts and inner enamel secretory ameloblasts were similar, but that
      those between differentiating preameloblasts and outer enamel secretory
      ameloblasts and between inner enamel secretory ameloblasts and outer enamel
      secretory ameloblasts were significantly different. Third, F-actin fluorescence
      microscopy in the distal terminal web was performed and was consistent with the
      angular distribution. These results suggest that cell shapes of inner enamel
      secretory ameloblasts and differentiating preameloblasts at the distal terminal
      web are specialized for sideways cell movement during decussating tooth enamel
      formation. 

PMID- 24285857
TI  - Sympathetic nervous system control of triglyceride metabolism: novel concepts
      derived from recent studies.
AB  - Important players in triglyceride (TG) metabolism include the liver (production),
      white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to
      generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the
      collective action of which determine plasma TG levels. Interestingly, recent
      evidence points to a prominent role of the hypothalamus in TG metabolism through
      innervating the liver, WAT, and BAT mainly via sympathetic branches of the
      autonomic nervous system. Here, we review the recent findings in the area of
      sympathetic control of TG metabolism. Various neuronal populations, such as
      neuropeptide Y (NPY)-expressing neurons and melanocortin-expressing neurons, as
      well as peripherally produced hormones (i.e., GLP-1, leptin, and insulin),
      modulate sympathetic outflow from the hypothalamus toward target organs and
      thereby influence peripheral TG metabolism. We conclude that sympathetic
      stimulation in general increases lipolysis in WAT, enhances VLDL-TG production by
      the liver, and increases the activity of BAT with respect to lipolysis of TG,
      followed by combustion of fatty acids toward heat. Moreover, the increased
      knowledge about the involvement of the neuroendocrine system in TG metabolism
      presented in this review offers new therapeutic options to fight
      hypertriglyceridemia by specifically modulating sympathetic nervous system
      outflow toward liver, BAT, or WAT. 

PMID- 24285862
TI  - Dispersion relations for coupled surface plasmon-polariton modes excited in
      multilayer structures.
AB  - The coupled surface plasmon-polariton (SPP) modes excited in an Al/SiO2/Al
      multilayer structure were analyzed using angle-resolved electron energy-loss
      spectroscopy (AREELS) with a relativistic electron probe. The dispersion
      relations for the coupled SPP modes were then directly observed and compared with
      predicted relations obtained via calculations. Good agreement was noted between
      the experimental and calculated results. In the multilayer structures, the
      dispersion relation for the coupled SPP modes was found to be sensitive to the
      thickness of each film, which could be interpreted qualitatively by the electron
      energy-loss probability calculated for thin aluminum (Al) films and narrow Al
      gaps using Kroger's formula. It was demonstrated that significant differences in
      the excitation probability for SPPs could be observed depending on the coupling
      modes. 

PMID- 24285863
TI  - Direct measurement of dispersion relation for surface plasmon-polaritons on
      silver nanoantennas.
AB  - We investigated the degree to which the dispersion relation of surface plasmon
      polaritons excited on silver nanoantennas depends on length. To accomplish this,
      dispersion measurements for individual silver nanoantennas with lengths from 220
      nm to 2.5 MUm were performed using angle-resolved electron energy-loss
      spectroscopy (AREELS) and spatially resolved EELS (SREELS). AREELS enabled
      measurements of the dispersion relation extending into the high-energy region of
      2.6 eV for a 2.5-MUm-long silver nanoantenna, without the need to excite Fabry
      Perot-type resonances. Our experiments showed that the dispersion relation of
      silver nanoantennas that have the same diameter is independent of their
      individual lengths. 

PMID- 24285865
TI  - Anesthetic regimes modulate the temporal dynamics of local field potential in the
      mouse olfactory bulb.
AB  - Anesthetized preparations have been widely used to study odor-induced temporal
      dynamics in the olfactory bulb. Although numerous recent data of single-cell
      recording or imaging in the olfactory bulb have employed ketamine cocktails,
      their effects on networks activities are still poorly understood, and odor
      induced oscillations of the local field potential have not been characterized
      under these anesthetics. Our study aimed at describing the impact of two ketamine
      cocktails on oscillations and comparing them to awake condition. Anesthesia was
      induced by injection of a cocktail of ketamine, an antagonist of the N-methyl-d
      aspartate receptors, combined with one agonist of alpha2-adrenergic receptors,
      xylazine (low affinity) or medetomidine (high affinity). Spontaneous and odor
      induced activities were examined in anesthetized and awake conditions, in the
      same mice chronically implanted with an electrode in the main olfactory bulb. The
      overall dynamic pattern of oscillations under the two ketamine cocktails
      resembles that of the awake state. Ongoing activity is characterized by gamma
      bursts (>60 Hz) locked on respiration and beta (15-40 Hz) power increases during
      odor stimulation. However, anesthesia decreases local field potential power and
      leads to a strong frequency shift of gamma oscillations from 60-90 Hz to 100-130
      Hz. We conclude that similarities between oscillations in anesthetized and awake
      states make cocktails of ketamine with one alpha2-agonist suitable for the
      recordings of local field potential to study processing in the early stages of
      the olfactory system. 

PMID- 24285864
TI  - Temporal properties of responses to sound in the ventral nucleus of the lateral
      lemniscus.
AB  - Besides the rapid fluctuations in pressure that constitute the "fine structure"
      of a sound stimulus, slower fluctuations in the sound's envelope represent an
      important temporal feature. At various stages in the auditory system, neurons
      exhibit tuning to envelope frequency and have been described as modulation
      filters. We examine such tuning in the ventral nucleus of the lateral lemniscus
      (VNLL) of the pentobarbital-anesthetized cat. The VNLL is a large but poorly
      accessible auditory structure that provides a massive inhibitory input to the
      inferior colliculus. We test whether envelope filtering effectively applies to
      the envelope spectrum when multiple envelope components are simultaneously
      present. We find two broad classes of response with often complementary
      properties. The firing rate of onset neurons is tuned to a band of modulation
      frequencies, over which they also synchronize strongly to the envelope waveform.
      Although most sustained neurons show little firing rate dependence on modulation
      frequency, some of them are weakly tuned. The latter neurons are usually band
      pass or low-pass tuned in synchronization, and a reverse-correlation approach
      demonstrates that their modulation tuning is preserved to nonperiodic, noisy
      envelope modulations of a tonal carrier. Modulation tuning to this type of
      stimulus is weaker for onset neurons. In response to broadband noise, sustained
      and onset neurons tend to filter out envelope components over a frequency range
      consistent with their modulation tuning to periodically modulated tones. The
      results support a role for VNLL in providing temporal reference signals to the
      auditory midbrain. 

PMID- 24285866
TI  - Effects of unilateral deactivations of dorsolateral prefrontal cortex and
      anterior cingulate cortex on saccadic eye movements.
AB  - The dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC)
      have both been implicated in the cognitive control of saccadic eye movements by
      single neuron recording studies in nonhuman primates and functional imaging
      studies in humans, but their relative roles remain unclear. Here, we reversibly
      deactivated either dlPFC or ACC subregions in macaque monkeys while the animals
      performed randomly interleaved pro- and antisaccades. In addition, we explored
      the whole-brain functional connectivity of these two regions by applying a seed
      based resting-state functional MRI analysis in a separate cohort of monkeys. We
      found that unilateral dlPFC deactivation had stronger behavioral effects on
      saccades than unilateral ACC deactivation, and that the dlPFC displayed stronger
      functional connectivity with frontoparietal areas than the ACC. We suggest that
      the dlPFC plays a more prominent role in the preparation of pro- and antisaccades
      than the ACC. 

PMID- 24285867
TI  - Persistent alpha1-adrenergic receptor function in the nucleus locus coeruleus
      causes hyperexcitability in AD/HD model rats.
AB  - Spontaneously hypertensive rats (SHR) are widely used as a model of attention
      deficit hyperactivity disorder (ADHD) as their ADHD-like behaviors are restored
      by methylphenidate. However, a postnatal neural development in SHR is unknown. We
      performed whole cell patch clamp recordings from locus coeruleus (LC) neurons in
      neonatal [postnatal day (P) 3-5], juvenile (P21-28), and adult (P 49-56) SHR and
      age-matched Wistar rats to evaluate alpha1- and alpha2-adrenergic receptor (ARs)
      activities at each developmental period. LC neurons in neonatal Wistar rats and
      SHR showed no difference in resting membrane potential and spontaneous firing
      rate, while juvenile and adult SHR LC neurons showed depolarized resting membrane
      potential and faster spontaneous firing rate than in Wistar rats. Blockade of
      alpha1-AR activity by prazosin hyperpolarized the membrane and abolished
      spontaneous firings in all developmental periods in SHR LC neurons, but not in
      juvenile and adult Wistar rats. alpha1-AR stimulation by phenylephrine evoked an
      inward current in juvenile LC neurons in SHR, but not in juvenile Wistar rats.
      This phenylephrine-induced inward current was abolished by nonselective cation
      channel blockers. By contrast, alpha2-AR stimulation-induced outward currents in
      the presence of an alpha1-AR antagonist were equivalent in SHR and Wistar LC
      neurons. These data suggest that Wistar LC neurons lose alpha1-AR function during
      development, whereas alpha1-ARs remain functional in SHR LC neurons. Thus
      persistent intrinsic activity of alpha1-ARs may be a neural mechanism
      contributing to developmental disorders in juvenile SHRs. 

PMID- 24285868
TI  - Trigeminal high-frequency stimulation produces short- and long-term modification
      of reflex blink gain.
AB  - Reflex blinks provide a model system for investigating motor learning in normal
      and pathological states. We investigated whether high-frequency stimulation (HFS)
      of the supraorbital branch of the trigeminal nerve before the R2 blink component
      (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB,
      Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in
      the first hour after treatment for rats. Repeated days of HFS-B treatment
      produced long-term depression of blink circuits. Blink gain decreased
      exponentially across days, indicating a long-term depression of blink circuits.
      Additionally, the HFS-B protocol became more effective at depressing blink
      amplitude across days of treatment. This depression was not habituation, because
      neither long- nor short-term blink changes occurred when HFS was presented after
      the R2. To investigate whether gain modifications produced by HFS-B involved
      cerebellar networks, we trained rats in a delay eyelid conditioning paradigm
      using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus.
      As HFS-B depresses blink circuits and delay conditioning enhances blink circuit
      activity, occlusion should occur if they share neural networks. Rats acquiring
      robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats
      developing low levels of eyelid conditioning exhibited weak, short-term
      reductions in blink gain. These results suggested that delay eyelid conditioning
      and long-term HFS-B utilize some of the same cerebellar circuits. The ability of
      repeated HFS-B treatment to depress trigeminal blink circuit activity long term
      implied that it may be a useful protocol to reduce hyperexcitable blink circuits
      that underlie diseases like benign essential blepharospasm. 

PMID- 24285869
TI  - Convergent synaptic inputs from the caudal fastigial nucleus and the superior
      colliculus onto pontine and pontomedullary reticulospinal neurons.
AB  - The caudal fastigial nucleus (FN) is known to be related to the control of eye
      movements and projects mainly to the contralateral reticular nuclei where
      excitatory and inhibitory burst neurons for saccades exist [the caudal portion of
      the nucleus reticularis pontis caudalis (NRPc), and the rostral portion of the
      nucleus reticularis gigantocellularis (NRG) respectively]. However, the exact
      reticular neurons targeted by caudal fastigioreticular cells remain unknown. We
      tried to determine the target reticular neurons of the caudal FN and superior
      colliculus (SC) by recording intracellular potentials from neurons in the NRPc
      and NRG of anesthetized cats. Neurons in the rostral NRG received bilateral,
      monosynaptic excitation from the caudal FNs, with contralateral predominance.
      They also received strong monosynaptic excitation from the rostral and caudal
      contralateral SC, and disynaptic excitation from the rostral ipsilateral SC.
      These reticular neurons with caudal fastigial monosynaptic excitation were not
      activated antidromically from the contralateral abducens nucleus, but most of
      them were reticulospinal neurons (RSNs) that were activated antidromically from
      the cervical cord. RSNs in the caudal NRPc received very weak monosynaptic
      excitation from only the contralateral caudal FN, and received either
      monosynaptic excitation only from the contralateral caudal SC, or monosynaptic
      and disynaptic excitation from the contralateral caudal and ipsilateral rostral
      SC, respectively. These results suggest that the caudal FN helps to control also
      head movements via RSNs targeted by the SC, and these RSNs with SC topographic
      input play different functional roles in head movements. 

PMID- 24285870
TI  - Noninvasive brain stimulation can elucidate and interact with the mechanisms
      underlying motor learning and retention: implications for rehabilitation.
AB  - Seminal work in animals indicates that learning a motor task results in long-term
      potentiation (LTP) in primary motor cortex (M1) and a subsequent occlusion of LTP
      induction (Rioult-Pedotti et al. J Neurophysiol 98: 3688-3695, 2007). Using
      various forms of noninvasive brain stimulation in conjunction with a motor
      learning paradigm, Cantarero et al. (J Neurosci 33: 12862-12869, 2013) recently
      provided novel evidence to support the hypothesis that retention of motor skill
      is contingent upon this postlearning occlusion. 

PMID- 24285871
TI  - Obesity that makes kidney cancer more likely but helps fight it more strongly.

PMID- 24285873
TI  - Rural-Nonrural Disparities in Postsecondary Educational Attainment Revisited.
AB  - Using data from the National Educational Longitudinal Study, this study revisited
      rural-nonrural disparities in educational attainment by considering a
      comprehensive set of factors that constrain and support youth's college
      enrollment and degree completion. Results showed that rural students were more
      advantaged in community social resources compared to nonrural students, and these
      resources were associated with a significant increase in the likelihood of
      bachelor's degree attainment. Yet results confirmed that rural students lagged
      behind nonrural students in attaining a bachelor's degree largely due to their
      lower socioeconomic background. The findings present a more comprehensive picture
      of the complexity of geographic residence in shaping college enrollment and
      degree attainment.

PMID- 24285872
TI  - An epidemiologic and genomic investigation into the obesity paradox in renal cell
      carcinoma.
AB  - BACKGROUND: Obesity increases risk for clear-cell renal cell carcinoma (ccRCC),
      yet obese patients appear to experience longer survival than nonobese patients.
      We examined body mass index (BMI) in relation to stage, grade, and cancer
      specific mortality (CSM) while considering detection bias, nutritional status,
      and molecular tumor features. METHODS: Data were available from 2119 ccRCC
      patients who underwent renal mass surgery at Memorial Sloan-Kettering Cancer
      Center between 1995 and 2012. Logistic regression models produced associations
      between BMI and advanced disease. Multivariable competing risks regression models
      estimated associations between BMI and CSM. Somatic mutation, copy number,
      methylation, and expression data were examined by BMI among a subset of 126
      patients who participated in the Cancer Genome Atlas Project for ccRCC using the
      Kruskal-Wallis or Fisher exact tests. All statistical tests were two-sided.
      RESULTS: Obese and overweight patients were less likely to present with advanced
      stage disease compared with normal-weight patients (odds ratio [OR] = 0.61, 95%
      confidence interval [CI] = 0.48 to 0.79 vs OR = 0.65, 95% CI = 0.51 to 0.83,
      respectively). Higher BMI was associated with reduced CSM in univariable analyses
      (P < .005). It remained statistically significant after adjustment for
      comorbidities and albumin level, but it became non-statistically significant
      after adjusting for stage and grade (P > .10). Genome-wide interrogation by BMI
      suggested differences in gene expression of metabolic and fatty acid genes,
      including fatty acid synthase (FASN), consistent with the obesity paradox.
      CONCLUSIONS: Our findings suggest that although BMI is not an independent
      prognostic factor for CSM after controlling for stage and grade, tumors
      developing in an obesogenic environment may be more indolent.

PMID- 24285874
TI  - Separation of Aliphatic and Aromatic Carboxylic Acids by Conventional and Ultra
      High Performance Ion Exclusion Chromatography.
AB  - An ion exclusion chromatography (IELC) comparison between a conventional ion
      exchange column and an ultra-high performance liquid chromatography (UHPLC)
      dynamically surfactant modified C18 column for the separation of an aliphatic
      carboxylic acid and two aromatic carboxylic acids is presented. Professional
      software is used to optimize the conventional IELC separation conditions for
      acetylsalicylic acid and the hydrolysis products: salicylic acid and acetic acid.
      Four different variables are simultaneously optimized including H2SO4
      concentration, pH, flow rate, and sample injection volume. Thirty different runs
      are suggested by the software. The resolutions and the time of each run are
      calculated and feed back to the software to predict the optimum conditions.
      Derringer's desirability functions are used to evaluate the test conditions and
      those with the highest desirability value are utilized to separate
      acetylsalicylic acid, salicylic acid, and acetic acid. These conditions include
      using a 0.35 mM H2SO4 (pH 3.93) eluent at a flow rate of 1 mL min-1 and an
      injection volume of 72 MUL. To decrease the run time and improve the performance,
      a UHPLC C18 column is used after dynamic modification with sodium dodecyl
      sulfate. Using pure water as a mobile phase, a shorter analysis time and better
      resolution are achieved. In addition, the elution order is different from the
      IELC method which indicates the contribution of the reversed-phase mode to the
      separation mechanism.

PMID- 24285875
TI  - The social life of the brain: Neuroscience in society.
AB  - Neuroscience is viewed by a range of actors and institutions as a powerful means
      of creating new knowledge about our selves and societies. This article documents
      the shifts in expertise and identities potentially being propelled by
      neuroscientific research. It details the framing and effects of neuroscience
      within several social domains, including education and mental health, discussing
      some of the intellectual and professional projects it has animated therein (such
      as neuroethics). The analysis attends to the cultural logics by which the brain
      is sometimes made salient in society; simultaneously, it points towards some of
      parameters of the territory within which the social life of the brain plays out.
      Instances of societal resistance and agnosticism are discussed, which may render
      problematic sociological research on neuroscience in society that assumes the
      universal import of neuroscientific knowledge (as either an object of celebration
      or critique). This article concludes with reflections on how sociotechnical
      novelty is produced and ascribed, and the implications of this.

PMID- 24285876
TI  - The ventromedial ventral pallidum subregion is necessary for outcome-specific
      Pavlovian-instrumental transfer.

PMID- 24285877
TI  - Functional integration of large-scale brain networks.

PMID- 24285879
TI  - Sodium and potassium currents influence Wallerian degeneration of injured
      Drosophila axons.
AB  - Axons degenerate after injury and in neuropathies and disease via a self
      destruction program whose mechanism is poorly understood. Axons that have lost
      connection to their cell bodies have altered electrical and synaptic activities,
      but whether such changes play a role in the axonal degeneration process is not
      clear. We have used a Drosophila model to study the Wallerian degeneration of
      motoneuron axons and their neuromuscular junction synapses. We found that
      degeneration of the distal nerve stump after a nerve crush is greatly delayed
      when there is increased potassium channel activity (by overexpression of two
      different potassium channels, Kir2.1 and dORKDelta-C) or decreased voltage-gated
      sodium channel activity (using mutations in the para sodium channel). Conversely,
      degeneration is accelerated when potassium channel activity is decreased (by
      expressing a dominant-negative mutation of Shaker). Despite the effect of
      altering voltage-gated sodium and potassium channel activity, recordings made
      after nerve crush demonstrated that the distal stump does not fire action
      potentials. Rather, a variety of lines of evidence suggest that the sodium and
      potassium channels manifest their effects upon degeneration through changes in
      the resting membrane potential, which in turn regulates the level of
      intracellular free calcium within the isolated distal axon. 

PMID- 24285878
TI  - A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2
      and BACHD mouse models of Huntington's disease.
AB  - Loss of neurotrophic support in the striatum caused by reduced brain-derived
      neurotrophic factor (BDNF) levels plays a critical role in Huntington's disease
      (HD) pathogenesis. BDNF acts via TrkB and p75 neurotrophin receptors (NTR), and
      restoring its signaling is a prime target for HD therapeutics. Here we sought to
      determine whether a small molecule ligand, LM22A-4, specific for TrkB and without
      effects on p75(NTR), could alleviate HD-related pathology in R6/2 and BACHD mouse
      models of HD. LM22A-4 was administered to R6/2 mice once daily (5-6 d/week) from
      4 to 11 weeks of age via intraperitoneal and intranasal routes simultaneously to
      maximize brain levels. The ligand reached levels in the R6/2 forebrain greater
      than the maximal neuroprotective dose in vitro and corrected deficits in
      activation of striatal TrkB and its key signaling intermediates AKT, PLCgamma,
      and CREB. Ligand-induced TrkB activation was associated with a reduction in HD
      pathologies in the striatum including decreased DARPP-32 levels, neurite
      degeneration of parvalbumin-containing interneurons, inflammation, and
      intranuclear huntingtin aggregates. Aggregates were also reduced in the cortex.
      Notably, LM22A-4 prevented deficits in dendritic spine density of medium spiny
      neurons. Moreover, R6/2 mice given LM22A-4 demonstrated improved downward
      climbing and grip strength compared with those given vehicle, though these groups
      had comparable rotarod performances and survival times. In BACHD mice, long-term
      LM22A-4 treatment (6 months) produced similar ameliorative effects. These results
      support the hypothesis that targeted activation of TrkB inhibits HD-related
      degenerative mechanisms, including spine loss, and may provide a disease
      mechanism-directed therapy for HD and other neurodegenerative conditions. 

PMID- 24285880
TI  - Motion-sensitive responses in visual area V4 in the absence of primary visual
      cortex.
AB  - Neurons in cortical ventral-stream area V4 are thought to contribute to important
      aspects of visual processing by integrating information from primary visual
      cortex (V1). However, how V4 neurons respond to visual stimulation after V1
      injury remains unclear: While electrophysiological investigation of V4 neurons
      during reversible V1 inactivation suggests that virtually all responses are
      eliminated (Girard et al., 1991), fMRI in humans and monkeys with permanent
      lesions shows reliable V1-independent activity (Baseler et al., 1999; Goebel et
      al., 2001; Schmid et al., 2010). To resolve this apparent discrepancy, we
      longitudinally assessed neuronal functions of macaque area V4 using chronically
      implanted electrode arrays before and after creating a permanent aspiration
      lesion in V1. During the month after lesioning, we observed weak yet significant
      spiking activity in response to stimuli presented to the lesion-affected part of
      the visual field. These V1-independent responses showed sensitivity for motion
      and likely reflect the effect of V1-bypassing geniculate input into extrastriate
      areas. 

PMID- 24285881
TI  - Enhancement of gamma oscillations indicates preferential processing of native
      over foreign phonemic contrasts in infants.
AB  - Young infants discriminate phonetically relevant speech contrasts in a universal
      manner, that is, similarly across languages. This ability fades by 12 months of
      age as the brain builds language-specific phonemic maps and increasingly responds
      preferentially to the infant's native language. However, the neural mechanisms
      that underlie the development of infant preference for native over non-native
      phonemes remain unclear. Since gamma-band power is known to signal infants'
      preference for native language rhythm, we hypothesized that it might also
      indicate preference for native phonemes. Using high-density
      electroencephalogram/event-related potential (EEG/ERP) recordings and source
      localization techniques to identify and locate the ERP generators, we examined
      changes in brain oscillations while 6-month-old human infants from monolingual
      English settings listened to English and Spanish syllable contrasts. Neural
      dynamics were investigated via single-trial analysis of the temporal-spectral
      composition of brain responses at source level. Increases in 4-6 Hz (theta) power
      and in phase synchronization at 2-4 Hz (delta/theta) were found to characterize
      infants' evoked responses to discrimination of native/non-native syllable
      contrasts mostly in the left auditory source. However, selective enhancement of
      induced gamma oscillations in the area of anterior cingulate cortex was seen only
      during native contrast discrimination. These results suggest that gamma
      oscillations support syllable discrimination in the earliest stages of language
      acquisition, particularly during the period in which infants begin to develop
      preferential processing for linguistically relevant phonemic features in their
      environment. Our results also suggest that by 6 months of age, infants already
      treat native phonemic contrasts differently from non-native, implying that
      perceptual specialization and establishment of enduring phonemic memory
      representations have been initiated. 

PMID- 24285882
TI  - Activity-dependent neurotrophin signaling underlies developmental switch of Ca2+
      channel subtypes mediating neurotransmitter release.
AB  - At the nerve terminal, neurotransmitter release is triggered by Ca(2+) influx
      through voltage-gated Ca(2+) channels (VGCCs). During postnatal development, VGCC
      subtypes in the nerve terminal switch at many synapses. In immature rodent
      cerebella, N-type and P/Q-type VGCCs mediate GABAergic neurotransmission from
      Purkinje cells (PCs) to deep nuclear cells, but as animals mature,
      neurotransmission becomes entirely P/Q-type dependent. We reproduced this
      developmental switch in rat cerebellar slice culture to address the underlying
      mechanism. Chronic block of cerebellar neuronal activity with tetrodotoxin (TTX)
      in slice culture, or in vivo, reversed the switch, leaving neurotransmission
      predominantly N-type channel-dependent. Brain-derived neurotrophic factor or
      neurotrophin-4 rescued this TTX effect, whereas pharmacological blockade of
      neurotrophin receptors mimicked the TTX effect. In PC somata, unlike in
      presynaptic terminals, TTX had no effect on the proportion of Ca(2+) channel
      subtype currents. We conclude that neuronal activity activates the neurotrophin
      TrkB signaling pathway, thereby causing the N-to-P/Q channel switch in
      presynaptic terminals. 

PMID- 24285883
TI  - Oligodendrocyte lineage cells contribute unique features to Rett syndrome
      neuropathology.
AB  - Mutations in the methyl-CpG binding protein 2 gene, Mecp2, affect primarily the
      brain and lead to a wide range of neuropsychiatric disorders, most commonly Rett
      syndrome (RTT). Although the neuropathology of RTT is well understood, the
      cellular and molecular mechanism(s), which lead to the disease initiation and
      progression, has yet to be elucidated. RTT was initially attributed only to
      neuronal dysfunction, but our recent studies and those of others show that RTT is
      not exclusively neuronal but rather also involves interactions between neurons
      and glia. Importantly, studies have shown that MeCP2-restored astrocytes and
      microglia are able to attenuate the disease progression in otherwise MeCP2-null
      mice. Here we show that another type of glia, oligodendrocytes, and their
      progenitors are also involved in manifestation of specific RTT symptoms. Mice
      that lost MeCP2 specifically in the oligodendrocyte lineage cells, although
      overall normal, were more active and developed severe hindlimb clasping
      phenotypes. Inversely, restoration of MeCP2 in oligodendrocyte lineage cells, in
      otherwise MeCP2-null mice, although only mildly prolonging their lifespan,
      significantly improved the locomotor deficits and hindlimb clasping phenotype,
      both in male and female mice, and fully restored the body weight in male mice.
      Finally, we found that the level of some myelin-related proteins was impaired in
      the MeCP2-null mice. Expression of MeCP2 in oligodendrocytes of these mice only
      partially restored their expression, suggesting that there is a non-cell
      autonomous effect by other cell types in the brains on the expression of myelin
      related proteins in oligodendrocytes. 

PMID- 24285884
TI  - Vocal corollary discharge communicates call duration to vertebrate auditory
      system.
AB  - Corollary discharge is essential to an animal's ability to filter self-generated
      from external stimuli. This includes acoustic communication, although direct
      demonstration of a corollary discharge that both conveys a vocal motor signal and
      informs the auditory system about the physical attributes of a self-generated
      vocalization has remained elusive for vertebrates. Here, we show the underlying
      synaptic activity of a neuronal vocal corollary discharge pathway in the
      hindbrain of a highly vocal species of fish. Neurons carrying the vocal corollary
      discharge are specifically adapted for the transmission of duration information,
      a predominant acoustic cue. The results reveal that vertebrates, like some
      insects, have a robust corollary discharge conveying call duration. Along with
      evidence for the influence of vocal duration on auditory encoding in mammals,
      these new findings suggest that linking vocal motor and corollary discharge
      pathways with pattern generating, call duration neurons is a shared network
      character across the animal kingdom. 

PMID- 24285885
TI  - Effective connectivity within human primary visual cortex predicts
      interindividual diversity in illusory perception.
AB  - Visual perception depends strongly on spatial context. A classic example is the
      tilt illusion where the perceived orientation of a central stimulus differs from
      its physical orientation when surrounded by tilted spatial contexts. Here we show
      that such contextual modulation of orientation perception exhibits trait-like
      interindividual diversity that correlates with interindividual differences in
      effective connectivity within human primary visual cortex. We found that the
      degree to which spatial contexts induced illusory orientation perception, namely,
      the magnitude of the tilt illusion, varied across healthy human adults in a trait
      like fashion independent of stimulus size or contrast. Parallel to contextual
      modulation of orientation perception, the presence of spatial contexts affected
      effective connectivity within human primary visual cortex between peripheral and
      foveal representations that responded to spatial context and central stimulus,
      respectively. Importantly, this effective connectivity from peripheral to foveal
      primary visual cortex correlated with interindividual differences in the
      magnitude of the tilt illusion. Moreover, this correlation with illusion
      perception was observed for effective connectivity under tilted contextual
      stimulation but not for that under iso-oriented contextual stimulation,
      suggesting that it reflected the impact of orientation-dependent intra-areal
      connections. Our findings revealed an interindividual correlation between intra
      areal connectivity within primary visual cortex and contextual influence on
      orientation perception. This neurophysiological-perceptual link provides
      empirical evidence for theoretical proposals that intra-areal connections in
      early visual cortices are involved in contextual modulation of visual perception.

PMID- 24285887
TI  - Motoneuron intrinsic properties, but not their receptive fields, recover in
      chronic spinal injury.
AB  - Proper movement execution relies on precise input processing by spinal
      motoneurons (MNs). Spinal MNs are activated by limb joint rotations. Typically,
      their movement-related receptive fields (MRRFs) are sharply focused and joint
      specific. After acute spinal transection MRRFs become wide, but their
      manifestation is not apparent, as intrinsic excitability, primarily resulting
      from the loss of persistent inward currents (PICs), dramatically decreases. PICs
      undergo a remarkable recovery with time after injury. Here we investigate whether
      MRRFs undergo a recovery that parallels that of the PIC. Using the chronic spinal
      cat in acute terminal decerebrate preparations, we found that MRRFs remain
      expanded 1 month after spinal transaction, whereas PICs recovered to >80% of
      their preinjury amplitudes. These recovered PICs substantially amplified the
      expanded inputs underlying the MRRFs. As a result, we show that single joint
      rotations lead to the activation of muscles across the entire limb. These results
      provide a potential mechanism for the propagation of spasms throughout the limb. 

PMID- 24285888
TI  - From image statistics to scene gist: evoked neural activity reveals transition
      from low-level natural image structure to scene category.
AB  - The visual system processes natural scenes in a split second. Part of this
      process is the extraction of "gist," a global first impression. It is unclear,
      however, how the human visual system computes this information. Here, we show
      that, when human observers categorize global information in real-world scenes,
      the brain exhibits strong sensitivity to low-level summary statistics. Subjects
      rated a specific instance of a global scene property, naturalness, for a large
      set of natural scenes while EEG was recorded. For each individual scene, we
      derived two physiologically plausible summary statistics by spatially pooling
      local contrast filter outputs: contrast energy (CE), indexing contrast strength,
      and spatial coherence (SC), indexing scene fragmentation. We show that behavioral
      performance is directly related to these statistics, with naturalness rating
      being influenced in particular by SC. At the neural level, both statistics
      parametrically modulated single-trial event-related potential amplitudes during
      an early, transient window (100-150 ms), but SC continued to influence activity
      levels later in time (up to 250 ms). In addition, the magnitude of neural
      activity that discriminated between man-made versus natural ratings of individual
      trials was related to SC, but not CE. These results suggest that global scene
      information may be computed by spatial pooling of responses from early visual
      areas (e.g., LGN or V1). The increased sensitivity over time to SC in particular,
      which reflects scene fragmentation, suggests that this statistic is actively
      exploited to estimate scene naturalness. 

PMID- 24285886
TI  - Monosynaptic glutamatergic activation of locus coeruleus and other lower
      brainstem noradrenergic neurons by the C1 cells in mice.
AB  - The C1 neurons, located in the rostral ventrolateral medulla (VLM), are activated
      by pain, hypotension, hypoglycemia, hypoxia, and infection, as well as by
      psychological stress. Prior work has highlighted the ability of these neurons to
      increase sympathetic tone, hence peripheral catecholamine release, probably via
      their direct excitatory projections to sympathetic preganglionic neurons. In this
      study, we use channelrhodopsin-2 (ChR2) optogenetics to test whether the C1 cells
      are also capable of broadly activating the brain's noradrenergic system. We
      selectively expressed ChR2(H134R) in rostral VLM catecholaminergic neurons by
      injecting Cre-dependent adeno-associated viral vectors into the brain of adult
      dopamine-beta-hydroxylase (DbetaH)(Cre/0) mice. Most ChR2-expressing VLM neurons
      (75%) were immunoreactive for phenylethanolamine N-methyl transferease, thus were
      C1 cells, and most of the ChR2-positive axonal varicosities were immunoreactive
      for vesicular glutamate transporter-2 (78%). We produced light microscopic
      evidence that the axons of rostral VLM (RVLM) catecholaminergic neurons contact
      locus coeruleus, A1, and A2 noradrenergic neurons, and ultrastructural evidence
      that these contacts represent asymmetric synapses. Using optogenetics in tissue
      slices, we show that RVLM catecholaminergic neurons activate the locus coeruleus
      as well as A1 and A2 noradrenergic neurons monosynaptically by releasing
      glutamate. In conclusion, activation of RVLM catecholaminergic neurons,
      predominantly C1 cells, by somatic or psychological stresses has the potential to
      increase the firing of both peripheral and central noradrenergic neurons. 

PMID- 24285889
TI  - Auditory artificial grammar learning in macaque and marmoset monkeys.
AB  - Artificial grammars (AG) are designed to emulate aspects of the structure of
      language, and AG learning (AGL) paradigms can be used to study the extent of
      nonhuman animals' structure-learning capabilities. However, different AG
      structures have been used with nonhuman animals and are difficult to compare
      across studies and species. We developed a simple quantitative parameter space,
      which we used to summarize previous nonhuman animal AGL results. This was used to
      highlight an under-studied AG with a forward-branching structure, designed to
      model certain aspects of the nondeterministic nature of word transitions in
      natural language and animal song. We tested whether two monkey species could
      learn aspects of this auditory AG. After habituating the monkeys to the AG,
      analysis of video recordings showed that common marmosets (New World monkeys)
      differentiated between well formed, correct testing sequences and those violating
      the AG structure based primarily on simple learning strategies. By comparison,
      Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A
      novel eye-tracking approach confirmed this result in the macaques and
      demonstrated evidence for more complex AGL. This study provides evidence for a
      previously unknown level of AGL complexity in Old World monkeys that seems less
      evident in New World monkeys, which are more distant evolutionary relatives to
      humans. The findings allow for the development of both marmosets and macaques as
      neurobiological model systems to study different aspects of AGL at the neuronal
      level. 

PMID- 24285890
TI  - The transcription factor serum response factor stimulates axon regeneration
      through cytoplasmic localization and cofilin interaction.
AB  - Axonal injury generates growth inert retraction bulbs with dynamic cytoskeletal
      properties that are severely compromised. Conversion of "frozen" retraction bulbs
      into actively progressing growth cones is a major aim in axon regeneration. Here
      we report that murine serum response factor (SRF), a gene regulator linked to the
      actin cytoskeleton, modulates growth cone actin dynamics during axon
      regeneration. In regeneration-competent facial motoneurons, Srf deletion
      inhibited axonal regeneration. In wild-type mice after nerve injury, SRF
      translocated from the nucleus to the cytoplasm, suggesting a cytoplasmic SRF
      function in axonal regeneration. Indeed, adenoviral overexpression of cytoplasmic
      SRF (SRF-DeltaNLS-GFP) stimulated axonal sprouting and facial nerve regeneration
      in vivo. In primary central and peripheral neurons, SRF-DeltaNLS-GFP stimulated
      neurite outgrowth, branch formation, and growth cone morphology. Furthermore, we
      uncovered a link between SRF and the actin-severing factor cofilin during axonal
      regeneration in vivo. Facial nerve axotomy increased the total cofilin abundance
      and also nuclear localization of phosphorylated cofilin in a subpopulation of
      lesioned motoneurons. This cytoplasmic-to-nucleus translocation of P-cofilin upon
      axotomy was reduced in motoneurons expressing SRF-DeltaNLS-GFP. Finally, we
      demonstrate that cytoplasmic SRF and cofilin formed a reciprocal regulatory unit.
      Overexpression of cytoplasmic SRF reduced cofilin phosphorylation and vice versa:
      overexpression of cofilin inhibited SRF phosphorylation. Therefore, a regulatory
      loop consisting of SRF and cofilin might take part in reactivating actin dynamics
      in growth-inert retraction bulbs and facilitating axon regeneration. 

PMID- 24285891
TI  - Propagating neocortical gamma bursts are coordinated by traveling alpha waves.
AB  - Neocortical neuronal activity is characterized by complex spatiotemporal
      dynamics. Although slow oscillations have been shown to travel over space in
      terms of consistent phase advances, it is unknown how this phenomenon relates to
      neuronal activity in other frequency bands. We here present electrocorticographic
      data from three male and one female human subject and demonstrate that gamma
      power is phase locked to traveling alpha waves. Given that alpha activity has
      been proposed to coordinate neuronal processing reflected in the gamma band, we
      suggest that alpha waves are involved in coordinating neuronal processing in both
      space and time. 

PMID- 24285892
TI  - Functional coupling from simple to complex cells in the visually driven cortical
      circuit.
AB  - In the classic model of the primary visual cortex, upper-layer complex cells are
      driven by feedforward inputs from layer 4 simple cells. Based on spike cross
      correlation, previous in vivo work has suggested that this connection is strong
      and dense, with a high probability of connection (50%) and significant strength
      in connected pairs. A much sparser projection has been found in brain slices,
      however, with the probability of layer 4 cells connecting to layer 2/3 cells
      being relatively low (10%). Here, we explore this connection in vivo in the cat
      primary visual cortex by recording simultaneously spikes of layer 4 simple cells
      and the membrane potential (V(m)) of layer 2/3 complex cells. By triggering the
      average of the complex cell's V(m) on the spikes of the simple cell (V(m)-STA),
      we found functional coupling to be very common during visual stimulation: the
      simple cell's spikes tended to occur near the troughs of the complex cell's V(m)
      fluctuations and were, on average, followed by a significant (~1 mV) fast-rising
      (10 ms) depolarization in the complex cell. In the absence of visual stimulation,
      however, when single simple cells were activated electrically through the
      recording electrode, no significant depolarization, or at most a very weak input
      (0.1-0.2 mV), was detected in the complex cell. We suggest that the functional
      coupling observed during visual stimulation arises from coordinated or nearly
      synchronous activity among a large population of simple cells, only a small
      fraction of which are presynaptic to the recorded complex cell.

PMID- 24285893
TI  - Terminator disparity contributes to stereo matching for eye movements and
      perception.
AB  - In the context of motion detection, the endings (or terminators) of 1-D features
      can be detected as 2-D features, affecting the perceived direction of motion of
      the 1-D features (the barber-pole illusion) and the direction of tracking eye
      movements. In the realm of binocular disparity processing, an equivalent role for
      the disparity of terminators has not been established. Here we explore the stereo
      analogy of the barber-pole stimulus, applying disparity to a 1-D noise stimulus
      seen through an elongated, zero-disparity, aperture. We found that, in human
      subjects, these stimuli induce robust short-latency reflexive vergence eye
      movements, initially in the direction orthogonal to the 1-D features, but shortly
      thereafter in the direction predicted by the disparity of the terminators. In
      addition, these same stimuli induce vivid depth percepts, which can only be
      attributed to the disparity of line terminators. When the 1-D noise patterns are
      given opposite contrast in the two eyes (anticorrelation), both components of the
      vergence response reverse sign. Finally, terminators drive vergence even when the
      aperture is defined by a texture (as opposed to a contrast) boundary. These
      findings prove that terminators contribute to stereo matching, and constrain the
      type of neuronal mechanisms that might be responsible for the detection of
      terminator disparity. 

PMID- 24285894
TI  - Distinct roles for MU-calpain and m-calpain in synaptic NMDAR-mediated
      neuroprotection and extrasynaptic NMDAR-mediated neurodegeneration.
AB  - Prolonged calpain activation is widely recognized as a key component of
      neurodegeneration in a variety of pathological conditions. Numerous reports have
      also indicated that synaptic activation of NMDA receptors (NMDARs) provides
      neuroprotection against a variety of insults. Here, we report the paradoxical
      finding that such neuroprotection involves calpain activation. NMDAR activation
      in cultured rat cortical neurons was neuroprotective against starvation and
      oxidative stress-induced damage. It also resulted in the degradation of two
      splice variants of PH domain and Leucine-rich repeat Protein Phosphatase 1
      (PHLPP1), PHLPP1alpha and PHLPP1beta, which inhibit the Akt and ERK1/2 pathways.
      Synaptic NMDAR-induced neuroprotection and PHLPP1 degradation were blocked by
      calpain inhibition. Lentiviral knockdown of PHLPP1 mimicked the neuroprotective
      effects of synaptic NMDAR activation and occluded the effects of calpain
      inhibition on neuroprotection. In contrast to synaptic NMDAR activation,
      extrasynaptic NMDAR activation had no effect on PHLPP1 and the Akt and ERK1/2
      pathways, but resulted in calpain-mediated degradation of striatal-enriched
      protein tyrosine phosphatase (STEP) and neuronal death. Using MU-calpain- and m
      calpain-selective inhibitors and MU-calpain and m-calpain siRNAs, we found that
      MU-calpain-dependent PHLPP1 cleavage was involved in synaptic NMDAR-mediated
      neuroprotection, while m-calpain-mediated STEP degradation was associated with
      extrasynaptic NMDAR-induced neurotoxicity. Furthermore, m-calpain inhibition
      reduced while MU-calpain knockout exacerbated NMDA-induced neurotoxicity in acute
      mouse hippocampal slices. Thus, synaptic NMDAR-coupled MU-calpain activation is
      neuroprotective, while extrasynaptic NMDAR-coupled m-calpain activation is
      neurodegenerative. These results help to reconcile a number of contradictory
      results in the literature and have critical implications for the understanding
      and potential treatment of neurodegenerative diseases. 

PMID- 24285896
TI  - Representational similarity analysis reveals commonalities and differences in the
      semantic processing of words and objects.
AB  - Understanding the meanings of words and objects requires the activation of
      underlying conceptual representations. Semantic representations are often assumed
      to be coded such that meaning is evoked regardless of the input modality.
      However, the extent to which meaning is coded in modality-independent or amodal
      systems remains controversial. We address this issue in a human fMRI study
      investigating the neural processing of concepts, presented separately as written
      words and pictures. Activation maps for each individual word and picture were
      used as input for searchlight-based multivoxel pattern analyses. Representational
      similarity analysis was used to identify regions correlating with low-level
      visual models of the words and objects and the semantic category structure common
      to both. Common semantic category effects for both modalities were found in a
      left-lateralized network, including left posterior middle temporal gyrus (LpMTG),
      left angular gyrus, and left intraparietal sulcus (LIPS), in addition to object-
      and word-specific semantic processing in ventral temporal cortex and more
      anterior MTG, respectively. To explore differences in representational content
      across regions and modalities, we developed novel data-driven analyses, based on
      k-means clustering of searchlight dissimilarity matrices and seeded correlation
      analysis. These revealed subtle differences in the representations in semantic
      sensitive regions, with representations in LIPS being relatively invariant to
      stimulus modality and representations in LpMTG being uncorrelated across
      modality. These results suggest that, although both LpMTG and LIPS are involved
      in semantic processing, only the functional role of LIPS is the same regardless
      of the visual input, whereas the functional role of LpMTG differs for words and
      objects. 

PMID- 24285895
TI  - Prenatal ethanol exposure disrupts intraneocortical circuitry, cortical gene
      expression, and behavior in a mouse model of FASD.
AB  - In utero ethanol exposure from a mother's consumption of alcoholic beverages
      impacts brain and cognitive development, creating a range of deficits in the
      child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol
      spectrum disorders (FASD) are often born with facial dysmorphology and may
      exhibit cognitive, behavioral, and motor deficits from ethanol-related
      neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is
      the number one cause of preventable mental and intellectual dysfunction globally,
      therefore the neurobiological underpinnings warrant systematic research. We
      document novel anatomical and gene expression abnormalities in the neocortex of
      newborn mice exposed to ethanol in utero. This is the first study to demonstrate
      large-scale changes in intraneocortical connections and disruption of normal
      patterns of neocortical gene expression in any prenatal ethanol exposure animal
      model. Neuroanatomical defects and abnormal neocortical RZRbeta, Id2, and
      Cadherin8 expression patterns are observed in PrEE newborns, and abnormal
      behavior is present in 20-d-old PrEE mice. The vast network of neocortical
      connections is responsible for high-level sensory and motor processing as well as
      complex cognitive thought and behavior in humans. Disruptions to this network
      from PrEE-related changes in gene expression may underlie some of the cognitive
      behavioral phenotypes observed in children with FASD. 

PMID- 24285897
TI  - Temporally dissociable mechanisms of self-control: early attentional filtering
      versus late value modulation.
AB  - Optimal decision-making often requires exercising self-control. A growing fMRI
      literature has implicated the dorsolateral prefrontal cortex (dlPFC) in
      successful self-control, but due to the limitations inherent in BOLD measures of
      brain activity, the neurocomputational role of this region has not been resolved.
      Here we exploit the high temporal resolution and whole-brain coverage of event
      related potentials (ERPs) to test the hypothesis that dlPFC affects dietary self
      control through two different mechanisms: attentional filtering and value
      modulation. Whereas attentional filtering of sensory input should occur early in
      the decision process, value modulation should occur later on, after the
      computation of stimulus values begins. Hungry human subjects were asked to make
      food choices while we measured neural activity using ERP in a natural condition,
      in which they responded freely and did not exhibit a tendency to regulate their
      diet, and in a self-control condition, in which they were given a financial
      incentive to lose weight. We then measured various neural markers associated with
      the attentional filtering and value modulation mechanisms across the decision
      period to test for changes in neural activity during the exercise of self
      control. Consistent with the hypothesis, we found evidence for top-down
      attentional filtering early on in the decision period (150-200 ms poststimulus
      onset) as well as evidence for value modulation later in the process (450-650 ms
      poststimulus onset). We also found evidence that dlPFC plays a role in the
      deployment of both mechanisms. 

PMID- 24285898
TI  - Serotonin and aversive Pavlovian control of instrumental behavior in humans.
AB  - Adaptive decision-making involves interaction between systems regulating
      Pavlovian and instrumental control of behavior. Here we investigate in humans the
      role of serotonin in such Pavlovian-instrumental transfer in both the aversive
      and the appetitive domain using acute tryptophan depletion, known to lower
      central serotonin levels. Acute tryptophan depletion attenuated the inhibiting
      effect of aversive Pavlovian cues on instrumental behavior, while leaving
      unaltered the activating effect of appetitive Pavlovian cues. These data suggest
      that serotonin is selectively involved in Pavlovian inhibition due to aversive
      expectations and have implications for our understanding of the mechanisms
      underlying a range of affective, impulsive, and aggressive neuropsychiatric
      disorders. 

PMID- 24285899
TI  - Forward suppression in the auditory cortex is caused by the Ca(v)3.1 calcium
      channel-mediated switch from bursting to tonic firing at thalamocortical
      projections.
AB  - Brief sounds produce a period of suppressed responsiveness in the auditory cortex
      (ACx). This forward suppression can last for hundreds of milliseconds and might
      contribute to mechanisms of temporal separation of sounds and stimulus-specific
      adaptation. However, the mechanisms of forward suppression remain unknown. We
      used in vivo recordings of sound-evoked responses in the mouse ACx and whole-cell
      recordings, two-photon calcium imaging in presynaptic terminals, and two-photon
      glutamate uncaging in dendritic spines performed in brain slices to show that
      synaptic depression at thalamocortical (TC) projections contributes to forward
      suppression in the ACx. Paired-pulse synaptic depression at TC projections lasts
      for hundreds of milliseconds and is attributable to a switch between firing modes
      in thalamic neurons. Thalamic neurons respond to a brief depolarizing pulse with
      a burst of action potentials; however, within hundreds of milliseconds, the same
      pulse repeated again produces only a single action potential. This switch between
      firing modes depends on Ca(v)3.1 T-type calcium channels enriched in thalamic
      relay neurons. Pharmacologic inhibition or knockdown of Ca(v)3.1 T-type calcium
      channels in the auditory thalamus substantially reduces synaptic depression at TC
      projections and forward suppression in the ACx. These data suggest that Ca(v)3.1
      dependent synaptic depression at TC projections contributes to mechanisms of
      forward suppression in the ACx.

PMID- 24285900
TI  - Alleviating pain hypersensitivity through activation of type 4 metabotropic
      glutamate receptor.
AB  - Hyperactivity of the glutamatergic system is involved in the development of
      central sensitization in the pain neuraxis, associated with allodynia and
      hyperalgesia observed in patients with chronic pain. Herein we study the ability
      of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate
      signaling and alleviate chronic pain. We show that mGlu4 are located both on
      unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the
      spinal cord where they inhibit glutamatergic transmission through coupling to
      Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong
      noxious mechanical compression and accelerates the onset of the nociceptive
      behavior in the inflammatory phase of the formalin test. However, responses to
      punctate mechanical stimulation and nocifensive responses to thermal noxious
      stimuli are not modified. Accordingly, pharmacological activation of mGlu4
      inhibits mechanical hypersensitivity in animal models of inflammatory or
      neuropathic pain while leaving acute mechanical perception unchanged in naive
      animals. Together, these results reveal that mGlu4 is a promising new target for
      the treatment of chronic pain. 

PMID- 24285901
TI  - Processing of hedonic and chemosensory features of taste in medial prefrontal and
      insular networks.
AB  - Most of the research on cortical processing of taste has focused on either the
      primary gustatory cortex (GC) or the orbitofrontal cortex (OFC). However, these
      are not the only areas involved in taste processing. Gustatory information can
      also reach another frontal region, the medial prefrontal cortex (mPFC), via
      direct projections from GC. mPFC has been studied extensively in relation to its
      role in controlling goal-directed action and reward-guided behaviors, yet very
      little is known about its involvement in taste coding. The experiments presented
      here address this important point and test whether neurons in mPFC can
      significantly process the physiochemical and hedonic dimensions of taste. Spiking
      responses to intraorally delivered tastants were recorded from rats implanted
      with bundles of electrodes in mPFC and GC. Analysis of single-neuron and ensemble
      activity revealed similarities and differences between the two areas. Neurons in
      mPFC can encode the chemosensory identity of gustatory stimuli. However,
      responses in mPFC are sparser, more narrowly tuned, and have a later onset than
      in GC. Although taste quality is more robustly represented in GC, taste
      palatability is coded equally well in the two areas. Additional analysis of
      responses in neurons processing the hedonic value of taste revealed differences
      between the two areas in temporal dynamics and sensitivities to palatability.
      These results add mPFC to the network of areas involved in processing gustatory
      stimuli and demonstrate significant differences in taste-coding between GC and
      mPFC. 

PMID- 24285902
TI  - The cingulo-opercular network provides word-recognition benefit.
AB  - Recognizing speech in difficult listening conditions requires considerable focus
      of attention that is often demonstrated by elevated activity in putative
      attention systems, including the cingulo-opercular network. We tested the
      prediction that elevated cingulo-opercular activity provides word-recognition
      benefit on a subsequent trial. Eighteen healthy, normal-hearing adults (10
      females; aged 20-38 years) performed word recognition (120 trials) in multi
      talker babble at +3 and +10 dB signal-to-noise ratios during a sparse sampling
      functional magnetic resonance imaging (fMRI) experiment. Blood oxygen level
      dependent (BOLD) contrast was elevated in the anterior cingulate cortex, anterior
      insula, and frontal operculum in response to poorer speech intelligibility and
      response errors. These brain regions exhibited significantly greater correlated
      activity during word recognition compared with rest, supporting the premise that
      word-recognition demands increased the coherence of cingulo-opercular network
      activity. Consistent with an adaptive control network explanation, general linear
      mixed model analyses demonstrated that increased magnitude and extent of cingulo
      opercular network activity was significantly associated with correct word
      recognition on subsequent trials. These results indicate that elevated cingulo
      opercular network activity is not simply a reflection of poor performance or
      error but also supports word recognition in difficult listening conditions. 

PMID- 24285904
TI  - Optimizing working memory with heterogeneity of recurrent cortical excitation.
AB  - A neural correlate of parametric working memory is a stimulus-specific rise in
      neuron firing rate that persists long after the stimulus is removed. Network
      models with local excitation and broad inhibition support persistent neural
      activity, linking network architecture and parametric working memory. Cortical
      neurons receive noisy input fluctuations that cause persistent activity to
      diffusively wander about the network, degrading memory over time. We explore how
      cortical architecture that supports parametric working memory affects the
      diffusion of persistent neural activity. Studying both a spiking network and a
      simplified potential well model, we show that spatially heterogeneous excitatory
      coupling stabilizes a discrete number of persistent states, reducing the
      diffusion of persistent activity over the network. However, heterogeneous
      coupling also coarse-grains the stimulus representation space, limiting the
      storage capacity of parametric working memory. The storage errors due to coarse
      graining and diffusion trade off so that information transfer between the initial
      and recalled stimulus is optimized at a fixed network heterogeneity. For
      sufficiently long delay times, the optimal number of attractors is less than the
      number of possible stimuli, suggesting that memory networks can under-represent
      stimulus space to optimize performance. Our results clearly demonstrate the
      combined effects of network architecture and stochastic fluctuations on
      parametric memory storage. 

PMID- 24285903
TI  - Effects of reversible spinalization on individual spinal neurons.
AB  - Postural limb reflexes (PLRs) represent a substantial component of the postural
      system responsible for stabilization of dorsal-side-up trunk orientation in
      quadrupeds. Spinalization causes spinal shock, that is a dramatic reduction of
      extensor tone and spinal reflexes, including PLRs. The goal of our study was to
      determine changes in activity of spinal interneurons, in particular those
      mediating PLRs, that is caused by spinalization. For this purpose, in decerebrate
      rabbits, activity of individual interneurons from L5 was recorded during
      stimulation causing PLRs under two conditions: (1) when neurons received
      supraspinal influences and (2) when these influences were temporarily abolished
      by a cold block of spike propagation in spinal pathways at T12 ("reversible
      spinalization"; RS). The effect of RS, that is a dramatic reduction of PLRs, was
      similar to the effect of surgical spinalization. In the examined population of
      interneurons (n = 199), activity of 84% of them correlated with PLRs, suggesting
      that they contribute to PLR generation. RS affected differently individual
      neurons: the mean frequency decreased in 67% of neurons, increased in 15%, and
      did not change in 18%. Neurons with different RS effects were differently
      distributed across the spinal cord: 80% of inactivated neurons were located in
      the intermediate area and ventral horn, whereas 50% of nonaffected neurons were
      located in the dorsal horn. We found a group of neurons that were coactivated
      with extensors during PLRs before RS and exhibited a dramatic (>80%) decrease in
      their activity during RS. We suggest that these neurons are responsible for
      reduction of extensor tone and postural reflexes during spinal shock. 

PMID- 24285905
TI  - Alleviating memory impairment through distraction.
AB  - Distraction typically has a negative impact on memory for recent events and
      patients with existing memory impairment are particularly vulnerable to
      distractor interference. In contrast, here we establish a beneficial effect for
      distractor presentation in humans for both patients with memory impairment due to
      bilateral hippocampal lesions and healthy adults with low memory performance.
      Recognition memory for images of place scenes, which had to be memorized for
      short delay periods was significantly improved with the presentation of a
      distractor face during the delay. Magnetoencephalography recordings of neural
      oscillations in the theta frequency range obtained in healthy adults suggest that
      this memory improvement results from the interruption of rehearsal by the
      distractor. Our results highlight circumstances where active memory rehearsal may
      paradoxically increase memory impairments and distraction alleviates these memory
      deficits in patients with hippocampal injury and healthy adults. 

PMID- 24285906
TI  - Load dependence of beta and gamma oscillations predicts individual capacity of
      visual attention.
AB  - Human capability to concurrently attend and perceive multiple visual objects has
      a limited and individual capacity of 2-4 objects. Neuronal mechanisms that
      support the perception of multiple objects and underlie these attentional
      capacity limits have remained unclear. We investigated the role of neuronal
      oscillations in multiobject visual perception and in limiting the attentional
      capacity. To this end, we used parametric multiobject tracking tasks, MEG and EEG
      recordings, and data-driven source-space analyses to localize the neuronal
      substrates of task performance. Three lines of evidence suggested a mechanistic
      role for neuronal oscillations in multiobject attention. First, oscillation
      amplitudes preceding target events were distinct for subsequently detected and
      undetected targets and also predicted reaction times to the target events.
      Second, suppression of theta to low-beta (<20 Hz) and strengthening of high-beta
      to gamma (20-90 Hz) oscillations in frontoparietal and visual regions were
      correlated with attentional load. Third, the load-dependent strengthening of
      gamma (30-90 Hz) band oscillations in lateral prefrontal, posterior parietal, and
      visual cortices predicted interindividual variability in attentional capacity. A
      progressive recruitment of gamma oscillations in sensory, attentional, and
      executive networks is thus directly correlated with multiobject attentional
      demands and, in particular, with the individual capability to consciously attend
      and perceive multiple visual objects concurrently. These data support the
      hypothesis that gamma oscillations contribute both to neuronal object
      representations and to attentional and executive processing. 

PMID- 24285908
TI  - Depth of focus enhancement of a modified imaging quasi-fractal zone plate.
AB  - We propose a new parameter w for optimization of foci distribution of
      conventional fractal zone plates (FZPs) with a greater depth of focus (DOF) in
      imaging. Numerical simulations of DOF distribution on axis directions indicate
      that the values of DOF can be extended by a factor of 1.5 or more by a modified
      quasi-FZP. In experiments, we employ a simple object-lens-image-plane arrangement
      to pick up images at various positions within the DOF of a conventional FZP and a
      quasi-FZP, respectively. Experimental results show that the parameter w improves
      foci distribution of FZPs in good agreement with theoretical predictions.

PMID- 24285907
TI  - Calcium-permeable AMPA receptors in the nucleus accumbens regulate depression
      like behaviors in the chronic neuropathic pain state.
AB  - Depression is a salient emotional feature of chronic pain. Depression alters the
      pain threshold and impairs functional recovery. To date, however, there has been
      limited understanding of synaptic or circuit mechanisms that regulate depression
      in the pain state. Here, we demonstrate that depression-like behaviors are
      induced in a rat model of chronic neuropathic pain. Using this model, we show
      that chronic pain selectively increases the level of GluA1 subunits of AMPA-type
      glutamate receptors at the synapses of the nucleus accumbens (NAc), a key
      component of the brain reward system. We find, in addition, that this increase in
      GluA1 levels leads to the formation of calcium-permeable AMPA receptors (CPARs).
      Surprisingly, pharmacologic blockade of these CPARs in the NAc increases
      depression-like behaviors associated with pain. Consistent with these findings,
      an AMPA receptor potentiator delivered into the NAc decreases pain-induced
      depression. These results show that transmission through CPARs in the NAc
      represents a novel molecular mechanism modulating the depressive symptoms of
      pain, and thus CPARs may be a promising therapeutic target for the treatment of
      pain-induced depression. More generally, these findings highlight the role of
      central glutamate signaling in pain states and define the brain reward system as
      an important region for the regulation of depressive symptoms of pain. 

PMID- 24285909
TI  - Revisiting the Role of Cultural Capital in East Asian Educational Systems: The
      Case of South Korea.
AB  - The concept of cultural capital has proved invaluable in understanding
      educational systems in Western countries, and recent work seeks to extend those
      insights to the diverse educational systems of other geographic regions. We
      explored cultural capital in South Korea by investigating the relationships among
      family socioeconomic status (SES), cultural capital, and children's academic
      achievement using data from the 2000 Programme for International Student
      Assessment. South Korea was compared with Japan, France, and the United States to
      understand how institutional features of South Korean education shape the role of
      cultural capital in academic success. Results showed that family SES had a
      positive effect on both parental objectified cultural capital and children's
      embodied cultural capital in South Korea, consistent with evidence from the other
      countries. Moreover, parental objectified cultural capital had a positive effect
      on children's academic achievement in South Korea. In contrast to other
      countries, however, children's embodied cultural capital had a negative effect on
      academic achievement in South Korea controlling for the other variables. We
      highlighted several institutional features of South Korean education including a
      standardized curriculum, extreme focus on test preparation, and extensive shadow
      education, which may combine to suppress the effect of children's embodied
      cultural capital on academic achievement.

PMID- 24285910
TI  - Patching the Pipeline: Reducing Educational Disparities in the Sciences Through
      Minority Training Programs.
AB  - For more than 40 years, there has been a concerted national effort to promote
      diversity among the scientific research community. Yet given the persistent
      national-level disparity in educational achievements of students from various
      ethnic and racial groups, the efficacy of these programs has come into question.
      The current study reports results from a longitudinal study of students supported
      by a national National Institutes of Health-funded minority training program, and
      a propensity score matched control. Growth curve analyses using Hierarchical
      Linear Modeling show that students supported by Research Initiative for Science
      Excellence were more likely to persist in their intentions to pursue a scientific
      research career. In addition, growth curve analyses indicate that undergraduate
      research experience, but not having a mentor, predicted student persistence in
      science.

PMID- 24285911
TI  - Bi-material attachment through a compliant interfacial system at the tendon-to
      bone insertion site.
AB  - The attachment of tendon to bone, one of the greatest interfacial material
      mismatches in nature, presents an anomaly from the perspective of interfacial
      engineering. Deleterious stress concentrations arising at bi-material interfaces
      can be reduced in engineering practice by smooth interpolation of composition,
      microstructure, and mechanical properties. However, following normal development,
      the rotator cuff tendon-to-bone "insertion site" presents an interfacial zone
      that is more compliant than either tendon or bone. This compliant zone is not
      regenerated following healing, and its absence may account for the poor outcomes
      observed following both natural and post-surgical healing of insertion sites such
      as those at the rotator cuff of the shoulder. Here, we present results of
      numerical simulations which provide a rationale for such a seemingly illogical
      yet effective interfacial system. Through numerical optimization of a
      mathematical model of an insertion site, we show that stress concentrations can
      be reduced by a biomimetic grading of material properties. Our results suggest a
      new approach to functional grading for minimization of stress concentrations at
      interfaces.

PMID- 24285912
TI  - Identifying Occupational Performance Barriers of Stroke Survivors: Utilization of
      a Home Assessment.
AB  - BACKGROUND: Stroke survivors often have impairments that make it difficult for
      them to function safely in their home environment. PURPOSE: The purpose of this
      study is to identify occupational performance barriers in the home and describe
      the subsequent recommendations offered to stroke survivors and their caregivers.
      METHODS: An occupational therapist administered a home safety tool to assess
      stroke survivors' home environments, determine home safety problems, and provide
      recommendations. FINDINGS: Among 76 stroke survivors, the greatest problems were
      indentified in the categories of bathroom, mobility, and communication. Two case
      studies illustrate the use of the home safety tool with this population.
      IMPLICATIONS: The home safety tool is helpful in determining the safety needs of
      stroke survivors living at home. We recommend the use of the home safety tool for
      occupational therapists assessing the safety of the home environment.

PMID- 24285914
TI  - Effects of Adolescent Childbearing on Latino Siblings: Changes in Family Dynamics
      and Feelings Toward the Teen Mother.
AB  - Latinos have had the highest teenage birthrate of any racial or ethnic group in
      the United States for the past 15 years, yet little is known about how Latino
      families are affected by a teenage daughter's childbearing. In-depth interviews
      were conducted with 32 Mexican American younger siblings of parenting teens to
      discern how their sister's childbearing had affected them and their families. The
      most commonly reported negative effects were increased family stress and
      conflict, more arguments with the parenting older sister, and less time spent
      with family members. Regarding benefits, all youth described a loving bond with
      their sister's baby, two thirds described their family becoming closer, and 81%
      felt closer to their older sister. The implications of these effects for Mexican
      American families are discussed.

PMID- 24285913
TI  - Association between -308 G/A TNF-alpha polymorphism and appendicular skeletal
      muscle mass index as a marker of sarcopenia in normal weight obese syndrome.
AB  - BACKGROUND AND AIM: Normal weight obese (NWO) syndrome is characterized by normal
      body mass index (BMI), but high amount of fat mass and reduced lean mass. We
      evaluated allelic frequency of the G/A -308 TNF-alpha polymorphism and prevalence
      of sarcopenia in NWO. METHODS: We enrolled 120 Italian healthy women,
      distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese
      (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X
      ray absorptiometry, blood tests, and genotyping of G/A -308 TNF-alpha
      polymorphism. RESULTS: We found a positive association between sarcopenic obesity
      and -308 TNF-alpha polymorphism. All obese women were sarcopenic and were no
      carrier of mutation (G/G). Among all G/G, NWO showed significant differences in
      lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P <
      0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW
      were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO
      subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were
      G/G. CONCLUSION: Our study suggests that TNF-alpha polymorphism contributes to
      sarcopenic obesity susceptibility, in association with body composition. This is
      the first study that shows the importance of TNF-alpha polymorphism to determine
      TBLean variation in NWO syndrome.

PMID- 24285915
TI  - Developmental Impacts of Child Abuse and Neglect Related to Adult Mental Health,
      Substance Use, and Physical Health.
AB  - This study examined the association between officially recorded child abuse and
      neglect and adult mental health, substance use, and physical health outcomes.
      Data are from a longitudinal study of more than 30 years in which individuals
      were interviewed most recently in their mid -30s. Analyses consisted of group
      comparisons using chi-square tests for categorical variables and independent
      samples t-tests for continuous measures. Logistic and linear regressions
      controlled for gender and childhood SES, adult age, marital status, and
      education. Adults maltreated in childhood reported more symptoms of adult
      depression, anxiety, and more impairment due to mental and physical health
      problems. A higher percentage of those with maltreatment histories reported
      lifetime alcohol problems and appear at greater risk for substance abuse. Most
      findings of these bivariate analyses remained significant after accounting for
      gender and childhood socioeconomic status. Somewhat fewer significant results
      were observed after controlling for adult age, marital status, and education.

PMID- 24285916
TI  - Selective Interarterial Radiation Therapy (SIRT) in Colorectal Liver Metastases:
      How Do We Monitor Response?
AB  - Radioembolisation is a way of providing targeted radiotherapy to colorectal liver
      metastases. Results are encouraging but there is still no standard method of
      assessing the response to treatment. This paper aims to review the current
      experience assessing response following radioembolisation. A literature review
      was undertaken detailing radioembolisation in the treatment of colorectal liver
      metastases comparing staging methods, criteria, and response. A search was
      performed of electronic databases from 1980 to November 2011. Information
      acquired included year published, patient numbers, resection status, chemotherapy
      regimen, criteria used to stage disease and assess response to radioembolisation,
      tumour markers, and overall/progression free survival. Nineteen studies were
      analysed including randomised controlled trials, clinical trials, meta-analyses,
      and case series. There is no validated modality as the method of choice when
      assessing response to radioembolisation. CT at 3 months following
      radioembolisation is the most frequently modality used to assess response to
      treatment. PET-CT is increasingly being used as it measures functional and
      radiological aspects. RECIST is the most frequently used criteria. Conclusion. A
      validated modality to assess response to radioembolisation is needed. We suggest
      PET-CT and CEA pre- and postradioembolisation at 3 months using RECIST 1.1
      criteria released in 2009, which includes criteria for PET-CT, cystic changes,
      and necrosis. 

PMID- 24285917
TI  - ICAT: Development of an Internet-Based Data Collection Method for Ecological
      Momentary Assessment Using Personal Cell Phones.
AB  - Rapid advances in mobile data-transfer technologies offer new possibilities in
      the use of cell phones to conduct assessments of a person's natural environment
      in real time. This paper describes features of a new Internet-based, cell phone
      optimized assessment technique (ICAT), which consists of a retrospective baseline
      assessment combined with text messages sent to the participants' personal cell
      phones providing a hyperlink to an Internet-stored cell phone-optimized
      questionnaire. Two participation conditions were used to test variations in
      response burden. Retention rates, completion rates, and response times in
      different subgroups were tested by means of chi2 tests, Cox regression, and
      logistic regression. Among the 237 initial participants, we observed a retention
      rate of 90.3% from the baseline assessment to the cell-phone part, and 80.4%
      repeated participation in the 30 daily assessments. Each day, 40-70% of the
      questionnaires were returned, a fourth in less than 3 minutes. Qualitative
      interviews underscored the ease of use of ICAT. This technique appears to be an
      innovative, convenient, and cost-effective way of collecting data on situational
      characteristics while minimizing recall bias. Because of its flexibility, ICAT
      can be applied in various disciplines, whether as part of small pilot studies or
      large-scale, crosscultural, and multisite research projects.

PMID- 24285918
TI  - Perseverance Furthers: Aims, Constraints, Effects, and Sympathy for Both Student
      and Nonstudent Sampling.

PMID- 24285919
TI  - Light as Therapy for Sleep Disorders and Depression in Older Adults.

PMID- 24285920
TI  - Can the anti-inflammatory activities of beta2-agonists be harnessed in the
      clinical setting?
AB  - Beta2-adrenoreceptor agonists (beta2-agonists) are primarily bronchodilators,
      targeting airway smooth muscle and providing critical symptomatic relief in
      conditions such as bronchial asthma and chronic obstructive pulmonary disease.
      These agents also possess broad-spectrum, secondary, anti-inflammatory
      properties. These are mediated largely, though not exclusively, via interactions
      with adenylyl cyclase-coupled beta2-adrenoreceptors on a range of immune and
      inflammatory cells involved in the immunopathogenesis of acute and chronic
      inflammatory disorders of the airways. The clinical relevance of the anti
      inflammatory actions of beta2-agonists, although often effective in the
      experimental setting, remains contentious. The primary objectives of the current
      review are: firstly, to assess the mechanisms, both molecular and cell
      associated, that may limit the anti-inflammatory efficacy of beta2-agonists;
      secondly, to evaluate pharmacological strategies, several of which are recent and
      innovative, that may overcome these limitations. These are preceded by a
      consideration of the various types of beta2-agonists, their clinical
      applications, and spectrum of anti-inflammatory activities, particularly those
      involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase
      mediated clearance of cytosolic calcium, and altered gene expression in immune
      and inflammatory cells. 

PMID- 24285922
TI  - Allergenicity and toxicology of inhaled silver nanoparticles in allergen
      provocation mice models.
AB  - Silver nanoparticles (AgNP) have been associated with the exacerbation of airway
      hyperresponsiveness. However, the allergenicity and toxicology of AgNP in healthy
      and allergic individuals are unclear. We investigated the pathophysiological
      responses to AgNP inhalation in a murine model of asthma. Continuous and stable
      levels of 33 nm AgNP were maintained at 3.3 mg/m(3) during the experimental
      period. AgNP exposure concomitant with ovalbumin challenge increased the enhanced
      pause (Penh) in the control and allergic groups. AgNP evoked neutrophil,
      lymphocyte and eosinophil infiltration into the airways and elevated the levels
      of allergic markers (immunoglobulin E [IgE] and leukotriene E4 [LTE4]), the type
      2 T helper (Th2) cytokine interleukin-13 (IL-13), and oxidative stress (8-hydroxy
      2'-deoxyguanosine [8-OHdG]) in healthy and allergic mice. Bronchocentric
      interstitial inflammation was observed after AgNP inhalation. After inhalation,
      the AgNP accumulated predominantly in the lungs, and trivial amounts of AgNP were
      excreted in the urine and feces. Furthermore, the AgNP induced inflammatory
      responses in the peritoneum. The inhalation of AgNP may present safety concerns
      in healthy and susceptible individuals. 

PMID- 24285921
TI  - Canagliflozin: a novel treatment option for type 2 diabetes.
AB  - Type 2 diabetes continues to be a challenging disease to manage. The addition of
      new agents with a positive risk-benefit ratio could potentially assist clinicians
      and patients in achieving adequate diabetes control. Canagliflozin, the first
      sodium-glucose cotransporter 2 inhibitor presently available on the market,
      offers a unique mechanism of action: it inhibits renal reabsorption of glucose,
      thereby increasing urinary glucose excretion. It reduces hemoglobin A1c by
      approximately 0.37%-1.16%; it also reduces the patient's weight and systolic
      blood pressure and has a low risk for hypoglycemia. Adverse effects include an
      increased risk of urinary tract infections and genital mycotic infections. In
      this manuscript we review canagliflozin and its potential role in management of
      type 2 diabetes mellitus. 

PMID- 24285924
TI  - Immunomagnetic nanoparticle-based assays for detection of biomarkers.
AB  - The emergence of biomarkers as key players in the paradigm shift towards
      preventative medicine underscores the need for their detection and
      quantification. Advances made in the field of nanotechnology have played a
      crucial role in achieving these needs, and have contributed to recent advances in
      the field of medicine. Nanoparticle-based immunomagnetic assays, in particular,
      offer numerous advantages that utilize the unique physical properties of magnetic
      nanoparticles. In this review, we focus on recent developments and trends with
      regards to immunomagnetic assays used for detection of biomarkers. The various
      immunomagnetic assays are categorized into the following: particle-based
      multiplexing, signal control, microfluidics, microarray, and automation. Herein,
      we analyze each category and discuss their advantages and disadvantages. 

PMID- 24285925
TI  - Prevalence of nontyphoidal Salmonella serogroups and their antimicrobial
      resistance patterns in a university teaching hospital in Eastern Province of
      Saudi Arabia.
AB  - BACKGROUND: Nontyphoidal Salmonella (NTS) species are important food-borne
      pathogens that cause gastroenteritis and bacteremia, and are responsible for a
      huge global burden of morbidity and mortality. The aim of this study was to
      investigate the prevalent serogroups and antibiotic resistance of NTS in our
      region. METHODS: We reviewed the serogroup distribution and antimicrobial
      susceptibility patterns of NTS strains obtained from 158 stool specimens of
      patients with acute diarrheal infection attending the outpatient and inpatient
      department at a university hospital in the Eastern Province of Saudi Arabia in
      the period from September, 2008 to April, 2011. A retrospective analysis of the
      158 patients with NTS infection was conducted to determine the most prevalent NTS
      serogroups causing acute gastroenteritis and their antimicrobial susceptibility
      patterns. RESULTS: At this teaching hospital, a total of 17,436 fecal samples
      were analyzed during the 2008-2011 study period. Of these specimens, 158 tested
      positive for NTS, giving an overall prevalence of 9.06 per 1,000. Of 158 NTS
      cases, serogroup D1 (25.3%) was the most prevalent, followed by serogroup B
      (19.6%), and serogroup C1 (18.9). One third of all NTS serogroup strains tested
      were resistant to tetracycline. The NTS strains showed resistance to ampicillin
      (31.3%), amoxicillin/clavulanic acid (29.9%), trimethoprim/sulfamethoxazole
      (20.9%), and cefotaxime (14.93%). CONCLUSION: The findings of this study support
      the concern that use of antibiotics in animal feeds may contribute to acquisition
      of resistance in food-borne bacteria, such as Salmonella. Our study also
      concludes that the prevalence of NTS in the Eastern Province of Saudi Arabia is
      very low compared with other studies worldwide.

PMID- 24285923
TI  - "One-stop shop" spectral imaging for rapid on-site diagnosis of lung cancer: a
      future concept in nano-oncology.
AB  - BACKGROUND: There are currently many techniques and devices available for the
      diagnosis of lung cancer. However, rapid on-site diagnosis is essential for early
      stage lung cancer, and in the current work we investigated a new diagnostic
      illumination nanotechnology. METHODS: Tissue samples were obtained from lymph
      nodes, cancerous tissue, and abnormal intrapulmonary lesions at our
      interventional pulmonary suites. The following diagnostic techniques were used to
      obtain the samples: endobronchial ultrasound bronchoscopy; flexible bronchoscopy;
      and rigid bronchoscopy. Flexible and rigid forceps were used because several of
      the patients were intubated using a rigid bronchoscope. In total, 30 tissue
      specimens from 30 patients were prepared. CytoViva(r) illumination nanotechnology
      was subsequently applied to each of the biopsy tissue slides. RESULTS: A spectral
      library was created for adenocarcinoma, epidermal growth factor receptor mutation
      positive adenocarcinoma, squamous cell carcinoma, usual interstitial pneumonitis,
      non-specific interstitial pneumonitis, typical carcinoid tumor, sarcoidosis,
      idiopathic pulmonary fibrosis, small cell neuroendocrine carcinoma, thymoma,
      epithelioid and sarcomatoid mesothelioma, cryptogenic organizing pneumonia, malt
      cell lymphoma, and Wegener's granulomatosis. CONCLUSION: The CytoViva software,
      once it had created a specific spectral library for each entity, was able to
      identify the same disease again in subsequent paired sets of slides of the same
      disease. Further evaluation of this technique could make this illumination
      nanotechnology an efficient rapid on-site diagnostic tool.

PMID- 24285926
TI  - Impact of glucose excursion and mean glucose concentration in oral glucose
      tolerance test on oxidative stress among Japanese Americans.
AB  - AIM: To evaluate the impact of glucose excursion (GE) and mean glucose
      concentration (MGC) on oxidative stress among persons with or without diabetes.
      MATERIALS AND METHODS: We examined 775 Japanese Americans who had normal glucose
      tolerance (NGT), impaired glucose tolerance, or diabetes according to the 75 g
      oral glucose-tolerance test, using fasting, 1-hour, and 2-hour glucose data. We
      calculated GE by subtracting the minimum from the maximum glucose level among
      three points and calculated MGC using these measurements. We investigated the
      relationship between GE or MGC and urinary isoprostane as a marker of oxidative
      stress. RESULTS: According to tertiles of GE or MGC, GE was associated with
      isoprostane levels among subjects with NGT as well as those with diabetes
      (P=0.004 and 0.033 for trend, respectively). However, MGC was associated with
      isoprostane only among NGT subjects (P=0.001 for trend). Association between GE
      and isoprostane was significant when adjustment was made for age, sex, smoking
      status, body mass index, C-reactive protein, glucose tolerance status, and
      homeostatic model assessment (P=0.029), but the association with MGC was not
      significant. CONCLUSION: Our results suggest the possibility that GE might result
      in oxidative stress, and the relationship is stronger than that for MGC.

PMID- 24285928
TI  - Social Structure Shapes Cultural Stereotypes and Emotions: A Causal Test of the
      Stereotype Content Model.
AB  - The stereotype content model (SCM) posits that social structure predicts specific
      cultural stereotypes and associated emotional prejudices. No prior evidence at a
      societal level has manipulated both structural predictors and measured both
      stereotypes and prejudices. In the present study, participants (n = 120)
      responded to an immigration scenario depicting a high- or low-status group,
      competitive or not competitive, and rated their likely stereotype (on warmth and
      competence) and elicited emotional prejudices (admiration, contempt, envy, and
      pity). Seven of eight specific predictions are fully confirmed, supporting the
      SCM's predicted causality for social structural effects on cultural stereotypes
      and emotional prejudices.

PMID- 24285927
TI  - Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin
      in the management of type 2 diabetes.
AB  - Exenatide once weekly (EQW), the first glucose-lowering agent for type 2 diabetes
      that is dosed one time per week, contains exenatide encapsulated in microspheres
      of a dissolvable matrix, which release active agent slowly and continuously into
      the circulation following subcutaneous injection. In two direct head-to-head
      comparisons, EQW resulted in better long-term glucose control, greater reductions
      in fasting plasma glucose, and more significant weight loss than sitagliptin. In
      other trials, glucose-lowering effects of EQW compared favorably with those of
      metformin, pioglitazone, and basal insulin. Patients on EQW exhibited a higher
      incidence of nausea than those on sitagliptin, although gastrointestinal adverse
      events occurred primarily during the first 6-8 weeks of therapy and declined
      thereafter. EQW was also associated with a lower incidence of nausea than two
      other glucagon-like peptide-1 receptor agonists, exenatide twice daily and
      liraglutide. Mild hypoglycemic episodes were uncommon with EQW, although risk of
      hypoglycemia increased in combination with sulfonylureas. When choosing between
      EQW and a dipeptidyl peptidase-4 (DPP-4) inhibitor, such as sitagliptin,
      clinicians and patients should consider the differences between the two
      medications in terms of glucose control (EQW superior to DPP-4 inhibitors),
      weight control (EQW superior to DPP-4 inhibitors), gastrointestinal tolerability
      during treatment initiation (EQW inferior to DPP-4 inhibitors), and mode of
      administration (once-weekly subcutaneous administration versus once-daily oral
      administration). 

PMID- 24285929
TI  - Exposure to triaryl phosphates: metabolism and biomarkers of exposure.
AB  - The leakage of tricresyl phosphate-containing engine lubricants into aircraft
      cabin air, either from worn or defective engine seals or under normal operating
      conditions, is a serious concern for both the health and safety of the cabin
      occupants, since the oil contains one to five percent tricresyl phosphate (TCP)
      esters, known neurotoxins. The exposure of pilots is a particular concern since
      their impairment can affect their safe operation of the aircraft. Mass
      spectrometric (MS)-based protocols for documenting exposures of individuals are
      described that entail a rapid purification of the TCP-modified plasma enzyme
      butyrylcholinesterase (BChE). Following protease digestion of BChE, the modified
      active site peptide is characterized by MS analysis. Approaches for identifying
      safer engine oil additives are also described. Some general comments regarding
      the necessity of improving the quality and safety of the cabin air supply are
      presented.

PMID- 24285930
TI  - Parts and Relations in Young Children's Shape-Based Object Recognition.
AB  - The ability to recognize common objects from sparse information about geometric
      shape emerges during the same period in which children learn object names and
      object categories. Hummel and Biederman's (1992) theory of object recognition
      proposes that the geometric shapes of objects have two components-geometric
      volumes representing major object parts, and the spatial relations among those
      parts. In the present research, 18- to 30-month-old children's ability to use
      separate information about object part shapes and part relations to recognize
      both novel (Experiment 1) and common objects (Experiment 2) was examined.
      Children succeeded in matching novel objects on part shapes despite differences
      in part relations but did not match on part relations when there were differences
      in part shapes. Given known objects, children showed that they did represent the
      relational structure of those objects. The results support the proposal that
      children's representations of the geometric structures of objects are built over
      time and may require exposure to multiple instances of an object category. More
      broadly, the results suggest that the distinction between object part shape and
      part relations as two components of object shape similarity is psychologically
      real and developmentally significant.

PMID- 24285931
TI  - Your Eyes Say "No," But Your Heart Says "Yes": Behavioral and Psychophysiological
      Indices in Infant Quantitative Processing.
AB  - Behavioral indices (e.g., infant looking) are predominantly used in studies of
      infant cognition, but psychophysiological measures have been increasingly
      integrated into common infant paradigms. The current study reports a result in
      which behavioral measures and physiological measures were both incorporated in a
      task designed to study infant number discrimination. Seven-month-old infants were
      habituated to several sets of stimuli varying in object type, but of a constant
      numerical value (either 2 or 3 items). Although looking time to each of the test
      trials revealed no differences, differences in heart-rate defined measures of
      attention revealed infants' ability to discriminate number. These findings imply
      that the inclusion of indices other than behavioral measures should become
      commonplace in studies of infant cognition.

PMID- 24285932
TI  - Expectations about single event probabilities in the first year of life: The
      influence of perceptual and statistical information.
AB  - Recent evidence suggests that infants can generate expectations about future
      events from a sample of probabilistic data. However, little is known about the
      conditions that support the development of this ability. Three experiments tested
      the prediction that 8- and 12-month-olds respond to base rates as well as
      perceptual cues when they generate expectations from a sample of probabilistic
      data. Results revealed that 12-month-olds were sensitive to the statistical and
      perceptual properties of the evidence depending on the distribution of high-to
      low base rate items in the sample. Specifically, 12-month-olds focused on
      perceptual features of the evidence when a sample was large and more skewed
      (e.g., 6:1), whereas they attended to statistical properties when the sample was
      smaller and less skewed (e.g., 4:1). In contrast, eight-month-olds always focused
      on the perceptual features of the evidence. Neither group generated expectations
      from a small, less skewed sample (e.g., 2:1). These results suggest that the
      ability to generate expectations about future events is mediated by specific
      features of the available evidence and undergoes significant change during the
      1st year of life.

PMID- 24285933
TI  - Ocular surface disorders in intensive care unit patients.
AB  - Patients in intensive care units (ICU) are at increased risk of corneal abrasions
      and infectious keratitis due to poor eyelid closure, decreased blink reflex, and
      increased exposure to pathogenic microorganisms. The aim of this retrospective
      study was to evaluate the ocular surface problems in patients who stayed in ICU
      more than 7 days and were consulted by an ophthalmologist. There were 26 men and
      14 women with a mean age of 40.1 +/- 18.15 years (range 17-74 years). Conjunctiva
      hyperemia, mucopurulent or purulent secretion, corneal staining, and corneal
      filaments were observed in 56.25%, 36.25%, 15%, and 5% of the eyes, respectively.
      Keratitis was observed in 4 patients (10%) who were treated successfully with
      topical antibiotics. Mean Schirmers test results were 7.6 +/- 5.7 mm/5 min
      (median 6.5 mm/5 min) in the right, and 7.9 +/- 6.3 mm/5 min (median 7 mm/5 min)
      in the left eyes. Schirmers test results were <5 mm/5 min in 40% of the subjects.
      The parameters did not show statistically significant difference according to
      mechanical ventilation, sedation, and use of inotropes. As ICU patients are more
      susceptible to develop dry eye, keratopathy, and ocular infections, they should
      be consulted by an ophthalmologist for early diagnosis of ocular surface
      disorders. 

PMID- 24285934
TI  - Genotoxic potential and physicochemical parameters of Sinos River, southern
      Brazil.
AB  - The present study aimed to evaluate the physicochemical parameters and the
      genotoxic potential of water samples collected in the upper, middle, and lower
      courses of the Sinos River, southern Brazil. The comet assay was performed in the
      peripheral blood of fish Hyphessobrycon luetkenii exposed under laboratory
      conditions to water samples collected in summer and winter in three sampling
      sites of Sinos River. Water quality analysis demonstrated values above those
      described in Brazilian legislation in Parobe and Sapucaia do Sul sites, located
      in the middle and in the lower courses of the Sinos River, respectively. The
      Caraa site, located in the upper river reach, presented all the physicochemical
      parameters in accordance with the allowed limits in both sampling periods. Comet
      assay in fish revealed genotoxicity in water samples collected in the middle
      course site in summer and in the three sites in winter when compared to control
      group. Thus, the physicochemical parameters indicated that the water quality of
      the upper course complies with the limits set by the national guidelines, and the
      ecotoxicological assessment, however, indicated the presence of genotoxic agents.
      The present study highlights the importance of combining water physicochemical
      analysis and bioassays to river monitoring. 

PMID- 24285935
TI  - Beliefs and attitudes of medical students from public and private universities in
      Malaysia towards individuals with HIV/AIDS.
AB  - We describe the findings from a survey assessing the beliefs regarding testing,
      confidentiality, disclosure, and environment of care and attitudes towards care
      of people with HIV/AIDS (PLHWA), in 1020, 4th and 5th year medical students, from
      public and private medical universities in Malaysia. A self-administered
      validated questionnaire based on the UNAIDS Model Questionnaire with a 5-point
      Likert scale (5, strongly disagree; 4, disagree; 3, neutral; 2, agree; 1,
      strongly agree) was used as a survey tool. The survey included demographic data
      and data on undergraduate training received on HIV/AIDS. Statistical significance
      in the demographic data and training received by respondents was evaluated using
      the chi-square test while the independent Student's t-test was used for
      comparison of means between public and private universities. A P value of <0.05
      was considered statistically significant with 95% confidence interval. Our study
      revealed less than 20% of medical students received adequate training to care for
      PLHWA. They had prevalent negative beliefs regarding testing, confidentiality,
      disclosure and environment of care towards PLHWA although in giving care to
      PLHWA, their attitudes were largely positive and nondiscriminatory. 

PMID- 24285936
TI  - On abelian and related fuzzy subsets of groupoids.
AB  - We introduce the notion of abelian fuzzy subsets on a groupoid, and we observe a
      variety of consequences which follow. New notions include, among others, diagonal
      symmetric relations, several types of quasi orders, convex sets, and fuzzy
      centers, some of whose properties are also investigated. 

PMID- 24285937
TI  - Viscosity-projection method for a family of general equilibrium problems and
      asymptotically strict pseudocontractions in the intermediate sense.
AB  - In this paper, a Meir-Keeler contraction is introduced to propose a viscosity
      projection approximation method for finding a common element of the set of
      solutions of a family of general equilibrium problems and the set of fixed points
      of asymptotically strict pseudocontractions in the intermediate sense. Strong
      convergence of the viscosity iterative sequences is obtained under some suitable
      conditions. Results presented in this paper extend and unify the previously known
      results announced by many other authors. 

PMID- 24285939
TI  - Recent Demographic Developments in France: Relatively Low Mortality at Advanced
      Ages.
AB  - France had 65.3 million inhabitants as of 1 January 2012, including 1.9 million
      in the overseas departements. The population is slightly younger than that of the
      European Union as a whole. Population growth continues at the same rate, mainly
      through natural increase. There are now more African than European immigrants
      living in France. Fertility was practically stable in 2011 (2.01 children per
      woman), but the lifetime fertility of the 1971-1972 cohorts reached a historic
      low in metropolitan France (1.99 children per woman), nevertheless remaining
      among the highest in Europe. Abortion levels remained stable and rates among
      young people are no longer increasing. The marriage rate is falling and the
      divorce rate has stabilized (46.2 divorces per 100 marriages in 2011). The risk
      of divorce decreases with age, but has greatly increased among the under-70s over
      the last decade. Life expectancy at birth (78.4 years for men, 85.0 for women)
      has continued to increase at the same rate, mainly thanks to progress at advanced
      ages. Among European countries, France has the lowest mortality in the over-65
      age group, but it ranks less well for premature mortality.

PMID- 24285938
TI  - Effects of metoprolol and nebivolol on exercise blood pressure in patients with
      mild hypertension.
AB  - OBJECTIVES: We planned to compare the impact of two beta blockers, metoprolol and
      nebivolol, on arterial blood pressure during exercise in patients with mild
      hypertension. METHODS: A total of 60 patients (13 males, 47 females; mean age:
      54.3 +/- 10.7 years) were enrolled in the present study. The patients were
      randomly selected to receive either nebivolol 5 mg/day (n = 30) or metoprolol 50
      mg/day (n = 30) for 8 weeks. At the end of the 8th week, each of the patients
      received exercise stress test according to Bruce protocol and their blood
      pressures were remeasured after rest, exercise, and recovery. RESULTS: Blood
      pressures were determined to be similar between metoprolol and nebivolol groups
      during rest, exercise, and recovery periods. Metoprolol and nebivolol achieved
      similar reductions in blood pressures during rest and exercise. However, five
      patients in nebivolol group and four patients in metoprolol group developed
      exaggerated BP response to exercise but the difference between metoprolol and
      nebivolol was not meaningful (P = 0.37). CONCLUSION: The results of the present
      study showed that metoprolol and nebivolol established comparable effects on the
      control of blood pressures during exercise in the patients with mild
      hypertensions.

PMID- 24285941
TI  - The frontiers of nuclear cardiology research.

PMID- 24285940
TI  - Novel functions of GABA signaling in adult neurogenesis.
AB  - Neurotransmitter gamma-aminobutiric acid (GABA) through ionotropic GABAA and
      metabotropic GABAB receptors plays key roles in modulating the development,
      plasticity and function of neuronal networks. GABA is inhibitory in mature
      neurons but excitatory in immature neurons, neuroblasts and neural
      stem/progenitor cells (NSCs/NPCs). The switch from excitatory to inhibitory
      occurs following the development of glutamatergic synaptic input and results from
      the dynamic changes in the expression of Na+/K+/2Cl- co-transporter NKCC1 driving
      Cl- influx and neuron-specific K+/Cl- co-transporter KCC2 driving Cl- efflux. The
      developmental transition of KCC2 expression is regulated by Disrupted-in
      Schizophrenia 1 (DISC1) and brain-derived neurotrophic factor (BDNF) signaling.
      The excitatory GABA signaling during early neurogenesis is important to the
      activity/experience-induced regulation of NSC quiescence, NPC proliferation,
      neuroblast migration and newborn neuronal maturation/functional integration. The
      inhibitory GABA signaling allows for the sparse and static functional networking
      essential for learning/memory development and maintenance.

PMID- 24285943
TI  - PET tracers and techniques for measuring myocardial blood flow in patients with
      coronary artery disease.
AB  - Assessment of the relative distribution of myocardial flow with myocardial
      perfusion imaging (MPI) is methodologically limited to predict the presence or
      absence of flow-limited coronary artery disease (CAD). This limitation may often
      occur, when obstructive lesions involve multiple epicardial coronary arteries or
      disease-related disturbances of the coronary circulation coexist at the
      microvascular level. Non-invasive assessment of myocardial blood flow in absolute
      units with position emission tomography (PET) has been positioned as the solution
      to improve CAD diagnosis and prediction of patient outcomes associated with risks
      for cardiac events. This article reviews technical and clinical aspects of
      myocardial blood flow quantitation with PET and discusses the practical
      consideration of this approach toward worldwide clinical utilization. 

PMID- 24285942
TI  - Multimodality image fusion for diagnosing coronary artery disease.
AB  - Coronary artery disease (CAD) is one of the leading causes of death in the US and
      a substantial health-care burden in all industrialized societies. In recent years
      we have witnessed a constant strive towards the development and the clinical
      application of novel or improved detection methods as well as therapies.
      Particularly, noninvasive imaging is a decisive component in the cardiovascular
      field. Image fusion is the ability of combining into a single integrated display
      the anatomical as well as the physiological data retrieved by separated
      modalities. Clinical evidence suggests that it represents a promising strategy in
      CAD assessment and risk stratification by significantly improving the diagnostic
      power of each modality independently considered and of the traditional side-by
      side interpretation. Numerous techniques and approaches taken from the image
      registration field have been implemented and validated in the context of CAD
      assessment and management. Although its diagnostic power is widely accepted,
      additional technical developments are still needed to become a routinely used
      clinical tool. 

PMID- 24285944
TI  - I -123 metaiodobenzylguanidine imaging for predicting ventricular arrhythmia in
      heart failure patients.
AB  - Compared to antiarrhythmic drugs, implantable cardioverter defibrillator (ICD)
      leads to a more significant improvement in preventing ventricular arrhythmia in
      heart failure patients. However, an important question has been raised that how
      to select appropriate patients for ICD therapy. I-123 metaiodobenzylguanidine
      (MIBG) planar and SPECT imaging have shown great potentials to predict
      ventricular arrhythmia in heart failure patients by assessing the abnormalities
      of the sympathetic nervous system. Clinical trials demonstrated that several
      parameters measured from I-123 MIBG planar and SPECT imaging, such as heart-to
      mediastinum ratio, washout rate, defect score, and innervation/perfusion
      mismatch, predicted ventricular arrhythmias in heart failure patients. This paper
      introduces the current practice of ICD therapy and reviews the technical
      background of I-123 MIBG planar and SPECT imaging and their clinical data in
      predicting ventricular arrhythmia. 

PMID- 24285945
TI  - Diagnosing CAD: additional markers from myocardial perfusion SPECT.
AB  - Over the past decades, stress/rest myocardial perfusion SPECT (MPS) has been
      utilized as a standard modality for the diagnosis, risk stratification and
      prognostic assessment of coronary artery disease (CAD). In addition to the
      perfusion information, MPS can also provide functional information of the left
      ventricle, including volume, ejection fraction, wall motion and dyssynchrony.
      This article introduces the incremental value of these non-perfusion parameters
      as markers and prognosticators of CAD. 

PMID- 24285947
TI  - The miR-183~96~182 cluster promotes tumorigenesis in a mouse model of
      medulloblastoma.
AB  - Medulloblastoma is the most common malignant pediatric brain tumor. Some are
      thought to originate from cerebellar granule neuron progenitors (CGNPs) that fail
      to undergo normal cell cycle exit and differentiation. The contribution of
      microRNAs to the initiation and progression of medulloblastoma remains poorly
      understood. Increased expression of the miR-183~96~182 cluster of microRNAs has
      been noted in several aggressive subgroups. We identified that expression of miR
      183~96~182 was higher in medulloblastomas with Pten gene loss in the background
      of the activated sonic hedgehog (Shh) signaling pathway. Ectopic miR-183~96~182
      expression in CGNPs synergized with exogenous Shh to increase proliferation and
      its role depended on hedgehog signaling activation. Our findings suggest a new
      microRNA cluster, the miR-183~96~182, functionally collaborates with the Shh
      signaling pathway in the development of medulloblastomas in mice. 

PMID- 24285946
TI  - Hypoxia-induced factor-1 alpha upregulates vascular endothelial growth factor C
      to promote lymphangiogenesis and angiogenesis in breast cancer patients.
AB  - Hypoxia-induced factor-1 alpha (HIF-1alpha) affects many effector molecules and
      regulates tumor lymphangiogenesis and angiogenesis during hypoxia. The aim of
      this study was to investigate the role of HIF-1alpha in the regulation of
      vascular endothelial growth factor C (VEGF-C) expression and its effect on
      lymphangiogenesis and angiogenesis in breast cancer. Lymphatic vessel density
      (LVD), microvessel density (MVD) and the expressions of HIF-1alpha and VEGF-C
      proteins were evaluated by immunohistochemistry in 75 breast cancer samples.
      There was a significant correlation between HIF-1alpha and VEGF-C (P = 0.014, r =
      0.273, Spearman's coefficient of correlation). HIF-1alpha and VEGF-C
      overexpression was significantly correlated with higher LVD (P = 0.003 and P =
      0.017, respectively), regional lymph nodal involvement (P = 0.002 and P = 0.004,
      respectively) and advanced tumor, node, metastasis (TNM) classification (P =
      0.001 and P = 0.01, respectively). Higher MVD was observed in the group
      expressing higher levels of HIF-1alpha and VEGF-C (P = 0.033 and P = 0.037,
      respectively). Univariate analysis showed shorter survival time in patients
      expressing higher levels of HIF-1alpha and VEGF-C. HIF-1alpha was also found to
      be an independent prognostic factor of overall survival in multivariate analysis.
      The results suggest that HIF-1alpha may affect VEGF-C expression, thus acting as
      a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This
      study highlights promising potential of HIF-1alpha as a therapeutic target
      against tumor lymph node metastasis. 

PMID- 24285948
TI  - Individual differences in transcranial electrical stimulation current density.
AB  - Transcranial electrical stimulation (TCES) is effective in treating many
      conditions, but it has not been possible to accurately forecast current density
      within the complex anatomy of a given subject's head. We sought to predict and
      verify TCES current densities and determine the variability of these current
      distributions in patient-specific models based on magnetic resonance imaging
      (MRI) data. Two experiments were performed. The first experiment estimated
      conductivity from MRIs and compared the current density results against actual
      measurements from the scalp surface of 3 subjects. In the second experiment,
      virtual electrodes were placed on the scalps of 18 subjects to model simulated
      current densities with 2 mA of virtually applied stimulation. This procedure was
      repeated for 4 electrode locations. Current densities were then calculated for 75
      brain regions. Comparison of modeled and measured external current in experiment
      1 yielded a correlation of r = .93. In experiment 2, modeled individual
      differences were greatest near the electrodes (ten-fold differences were common),
      but simulated current was found in all regions of the brain. Sites that were
      distant from the electrodes (e.g. hypothalamus) typically showed two-fold
      individual differences. MRI-based modeling can effectively predict current
      densities in individual brains. Significant variation occurs between subjects
      with the same applied electrode configuration. Individualized MRI-based modeling
      should be considered in place of the 10-20 system when accurate TCES is needed. 

PMID- 24285949
TI  - Volume conduction energy transfer for implantable devices.
AB  - A common model of power supply for implantable devices was established to study
      factors affecting volume conduction energy transfer. Electromagnetic and
      equivalent circuit models were constructed to study the effect of separation
      between the source electrode pairs on volume conduction energy transfer. In
      addition, the parameters of external signal including waveform, amplitude and
      frequency were analyzed. As the current amplitude did not lead to tissue injury
      and the current frequency did not cause nerve excitability, the recommended
      separation between the source electrodes was 3 cm, the proposed waveform of
      signal source was sinusoidal wave and the optimal frequency was 200 KHz. In agar
      experiment and swine skin experiment, the current transfer efficiencies were
      28.13% and 20.65%, respectively, and the energy transfer efficiencies were 9.86%
      and 6.90%, respectively. In conclusion, we can achieve optimal efficiency of
      energy transfer by appropriately setting the separation between the source
      electrode parameters of the signal source. 

PMID- 24285951
TI  - Human blood plasma-based electronic integrated circuit amplifier configuration.

PMID- 24285950
TI  - Pulmonary cystic disease associated with integumentary and renal manifestations.
AB  - A 69-year-old man with multiple skin lesions on his face, neck and upper torso,
      which first appeared in the 3rd decade of his life, was admitted to our hospital.
      He had cystic changes in his lungs noted on chest computed tomography (CT)
      scanning, as well as a left kidney mass. This patient exhibited a rare complex of
      renal, cutaneous and pulmonary manifestations, eponymously named Birt-Hogg-Dube
      syndrome, with characteristic skin features (fibrofolliculomas, trichodiscomas
      and acrochordons). This syndrome is due to an autosomal dominant germ-line
      mutation of the folliculin (FLCN) gene located at chromosome 17p11.2. Diagnosis
      and differentiation from other disease complexes including the skin, kidneys and
      lungs are important in prognostication and management of potentially life
      threatening complications such as renal cell carcinoma and pneumothoraces. 

PMID- 24285952
TI  - The PPAR alpha / gamma Agonist, Tesaglitazar, Improves Insulin Mediated Switching
      of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker
      Rat.
AB  - METABOLIC FLEXIBILITY WAS ASSESSED IN MALE ZUCKER RATS: lean controls, obese
      controls, and obese rats treated with the dual peroxisome proliferator activated
      receptor (PPAR) alpha/gamma agonist, tesaglitazar, 3  MU mol/kg/day for 3 weeks.
      Whole body glucose disposal rate (R d ) and hepatic glucose output (HGO) were
      assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions
      using [3,(3)H]glucose. Indices of tissue specific glucose utilization (R g ')
      were measured at basal, physiological, and supraphysiological levels of
      insulinemia using 2-deoxy-D-[2,6-(3)H]glucose. Finally, whole body and tissue
      specific FFA and glucose utilization and metabolic fate were evaluated under
      basal and hyperinsulinemic conditions using a combination of [U-(13)C]glucose, 2
      deoxy-D-[U-(14)C]glucose, [U-(14)C]palmitate, and [9,10-(3)H]-(R)-bromopalmitate.
      Tesaglitazar improved whole body insulin action by greater suppression of HGO and
      stimulation of R d compared to obese controls. This involved increased insulin
      stimulation of R g ' in fat and skeletal muscle as well as increased glycogen
      synthesis. Tesaglitazar dramatically improved insulin mediated suppression of
      plasma FFA level, whole body turnover (R fa ), and muscle, liver, and fat
      utilization. At basal insulin levels, tesaglitazar failed to lower HGO or R fa
      compared to obese controls. In conclusion, the results demonstrate that
      tesaglitazar has a remarkable ability to improve insulin mediated control of
      glucose and FFA fluxes in obese Zucker rats.

PMID- 24285953
TI  - Negative pressure wound therapy for the treatment of the open abdomen and
      incidence of enteral fistulas: a retrospective bicentre analysis.
AB  - Introduction. The open abdomen (OA) is often associated with complications. It
      has been hypothesized that negative pressure wound therapy (NPWT) in the
      treatment of OA may provoke enteral fistulas. Therefore, we analyzed patients
      with OA and NPWT with special regard to the occurrence of intestinal fistulas.
      Methods. The present study included all consecutive patients with OA treated with
      NWPT from April 2010 to August 2011 in two hospitals. Patients' demographics,
      indications for OA, risk factors, complications, outcome and incidence of
      fistulas before, during and after NPWT were recorded. Results. Of 81 patients
      with OA, 26 had pre-existing fistulas and 55 were free from a fistula at the
      beginning of NPWT. Nine of the 55 patients developed fistulas during (n = 5) or
      after NPWT (n = 4). Seventy-five patients received ABThera therapy, 6 patients
      other temporary abdominal closure devices. Only diverticulitis seemed to be a
      significant predisposing factor for fistulas. Mortality was slightly lower for
      patients without fistulas. Conclusion. The present study revealed no correlation
      between occurrence of fistulas before, during, and after NWPT, with
      diverticulitis being the only risk factor. Fistula formation during NPWT was
      comparable to reports from literature. Prospective studies are mandatory to
      clarify the impact of NPWT on fistula formation. 

PMID- 24285954
TI  - In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and
      Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe
      drug hypersensitivities with high mortality. Typical over-the-counter drugs of
      cold medicines are suggested to be causative. As multiple ingredients are
      generally contained in cold medicines, it is of particular interest to
      investigate which ingredients are responsible for SJS/TEN. However, experimental
      examination of causal relationships between SJS/TEN and a particular drug
      molecule is not straightforward. Significant association between HLA-A*02:06 and
      SJS/TEN with severe ocular surface complications has been observed in the
      Japanese. In the present study, we have undertaken in silico docking simulations
      between various ingredients contained in cold medicines available in Japan and
      the HLA-A*02:06 molecule. We use the composite risk index (CRI) that is the
      absolute value of the binding affinity multiplied by the daily dose to assess the
      potential risk of the adverse reactions. The drugs which have been recognized as
      causative drugs of SJS/TEN in Japan have revealed relatively high CRI, and the
      association between SJS/TEN and HLA-A*02:06 has been qualitatively verified. The
      results have also shown that some drugs whose links to SJS/TEN have not been
      clinically recognized in Japan show the high CRI and suggested that attention
      should be paid to their adverse drug reactions. 

PMID- 24285955
TI  - Multidisciplinary approach to the treatment of obese adolescents: effects on
      cardiovascular risk factors, inflammatory profile, and neuroendocrine regulation
      of energy balance.
AB  - The prevention of obesity and health concerns related to body fat is a major
      challenge worldwide. The aim of this study was to investigate the role of a
      medically supervised, multidisciplinary approach, on reduction in the prevalence
      of obesity related comorbidities, inflammatory profile, and neuroendocrine
      regulation of energy balance in a sample of obese adolescents. A total of 97
      postpuberty obese adolescents were enrolled in this study. Body composition,
      neuropeptides, and adipokines were analysed. The metabolic syndrome was defined
      by the International Diabetes Federation (IDF). The abdominal ultrasonography was
      performed to measure visceral, subcutaneous fat and hepatic steatosis. All
      measures were performed at baseline and after one year of therapy. The
      multidisciplinary management promoted the control of obesity reducing body fat
      mass. The prevalence of metabolic syndrome, asthma, nonalcoholic fatty liver
      disease (NAFLD), binge eating, and hyperleptinemia was reduced. An improvement in
      the inflammatory profile was demonstrated by an increase in anti-inflammatory
      adiponectin and reduction in proinflammatory adipokines, plasminogen activator
      inhibitor-1, interleukin-6 concentrations, and in the Lep/Adipo ratio. Moreover,
      a reduction in the AgRP and an increase in the alfa-MSH were noted. The
      multidisciplinary approach not only reduced obesity but also is efficacious in
      cardiovascular risk factors, inflammatory profile, and neuroendocrine regulation
      of energy balance. 

PMID- 24285956
TI  - Bone-Forming Capabilities of a Newly Developed NanoHA Composite Alloplast Infused
      with Collagen: A Pilot Study in the Sheep Mandible.
AB  - Lateral or vertical bone augmentation has always been a challenge, since the site
      is exposed to constant pressure from the soft tissue, and blood supply only
      exists from the donor site. Although, for such clinical cases, onlay grafting
      with autogenous bone is commonly selected, the invasiveness of the secondary
      surgical site and the relatively fast resorption rate have been reported as a
      drawback, which motivated the investigation of alternative approaches. This study
      evaluated the bone-forming capability of a novel nanoHA alloplast infused with
      collagen graft material made from biodegradable polylactic acid/polyglycolic acid
      versus a control graft material with the same synthesized alloplast without the
      nanoHA component and collagen infiltration. The status of newly formed bone and
      the resorption of the graft material were evaluated at 6 weeks in vivo
      histologically and three dimensionally by means of 3D microcomputed tomography.
      The histologic observation showed that newly formed bone ingrowth and internal
      resorption of the block were observed for the experimental blocks, whereas for
      the control blocks less bone ingrowth occurred along with lower resorption rate
      of the block material. The three-dimensional observation indicated that the
      experimental block maintained the external geometry, but at the same time
      successfully altered the graft material into bone. It is suggested that the
      combination of numerous factors contributed to the bone ingrowth and the novel
      development could be an alternative bone grafting choice. 

PMID- 24285957
TI  - Evaluating two oral health video interventions with early head start families.
AB  - Poor oral health in early childhood can have long-term consequences, and parents
      often are unaware of the importance of preventive measures for infants and
      toddlers. Children in rural, low-income families suffer disproportionately from
      the effects of poor oral health. Participants were 91 parents of infants and
      toddlers enrolled in Early Head Start (EHS) living in rural Hawai'i, USA. In this
      quasi-experimental design, EHS home visitors were assigned to use either a
      didactic or family-centered video with parents they served. Home visitors
      reviewed short segments of the assigned videos with parents over an eight-week
      period. Both groups showed significant prepost gains on knowledge and
      attitudes/behaviors relating to early oral health as well as self-reported
      changes in family oral health routines at a six-week followup. Controlling for
      pretest levels, parents in the family-centered video group showed larger changes
      in attitudes/behaviors at posttest and a higher number of positive changes in
      family oral health routines at followup. Results suggest that family-centered
      educational videos are a promising method for providing anticipatory guidance to
      parents regarding early childhood oral health. Furthermore, establishing
      partnerships between dental care, early childhood education, and maternal health
      systems offers a model that broadens potential reach with minimal cost. 

PMID- 24285958
TI  - U1 snRNP-Dependent Suppression of Polyadenylation: Physiological Role and
      Therapeutic Opportunities in Cancer.
AB  - Pre-mRNA splicing and polyadenylation are critical steps in the maturation of
      eukaryotic mRNA. U1 snRNP is an essential component of the splicing machinery and
      participates in splice-site selection and spliceosome assembly by base-pairing to
      the 5' splice site. U1 snRNP also plays an additional, nonsplicing global
      function in 3' end mRNA processing; it actively suppresses the polyadenylation
      machinery from using early, mostly intronic polyadenylation signals which would
      lead to aberrant, truncated mRNAs. Thus, U1 snRNP safeguards pre-mRNA transcripts
      against premature polyadenylation and contributes to the regulation of
      alternative polyadenylation. Here, we review the role of U1 snRNP in 3' end mRNA
      processing, outline the evidence that led to the recognition of its
      physiological, general role in inhibiting polyadenylation, and finally highlight
      the possibility of manipulating this U1 snRNP function for therapeutic purposes
      in cancer. 

PMID- 24285960
TI  - Achievement of therapeutic goals with low-dose imiglucerase in Gaucher disease: a
      single-center experience.
AB  - Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with
      variable and unpredictable onset and severity. Disease-specific enzyme
      replacement therapy (ERT) has been shown to reverse or ameliorate disease
      specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts
      bone manifestations, including bone crises, bone pain, and appearance of new
      osteonecrosis, and improves bone mineral density to varying degrees. The
      objective of this study was to assess achievement of predefined therapeutic goals
      based on international registry outcomes for Israeli patients with Gaucher
      disease receiving imiglucerase for four consecutive years on a low-dose regimen
      followed in a single center. All data were taken from patient files. The
      therapeutic goals were taken from standards published in the literature for
      disease-specific clinical parameters. Among 164 patients at baseline, values for
      spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar
      spine and femoral were significantly different from the goal. After four years
      ERT, there was a significant improvement (P = 0.000) in each of the therapeutic
      goal parameters from baseline. 15.2% of these patients achieved all hematology
      visceral goals. In children, there was achievement of linear growth and puberty.
      This survey highlights the good overall response in symptomatic patients
      receiving low-dose ERT with imiglucerase in Israel. 

PMID- 24285962
TI  - Statin Prescription Adhered to Guidelines for Patients Hospitalized due to Acute
      Ischemic Stroke or Transient Ischemic Attack.
AB  - BACKGROUND AND PURPOSE: Secondary stroke prevention guidelines recommend statins
      for the management of dyslipidemia in ischemic stroke and transient ischemic
      attack (TIA). This study assessed the guideline-based statin prescription (GBSP)
      rate in Korea and the associated physician and patient factors. METHODS: A survey
      was conducted to assess Korean neurologists' knowledge of and attitude toward the
      current dyslipidemia management guidelines. The characteristics and discharge
      statin prescription for all consecutive patients with acute ischemic stroke or
      TIA treated by participating neurologists during the 6 months prior to the survey
      were abstracted. Using algorithms to determine GBSP, we assessed the rate and
      independent factors of GBSP. RESULTS: Of the 174 participating neurologists, 79
      (45.4%) were categorized as a higher-level knowledge group. For the 4407 patients
      (mean age, 66.4 years; female, 42.5%; 90.6% with ischemic stroke and 9.4% with
      TIA) enrolled in this study, the GBSP rate at discharge was 78.6%. The GBSP rate
      increased significantly with increasing physician knowledge level (test for
      trend, p<0.0001), and was higher among patients treated by the higher-level
      knowledge group than for those treated by the lower-level knowledge group (81.6%
      vs. 74.7%; unadjusted p<0.0001 and adjusted p=0.045). Other independent factors
      associated with a higher GBSP rate were hypercholesterolemia and higher low
      density lipoprotein cholesterol level, while those associated with a lower GBSP
      rate were cardioembolism, undetermined etiology due to negative or incomplete
      work-up, other determined etiology, and TIA presentation. CONCLUSIONS: More than
      three-quarters of acute ischemic stroke survivors and TIA patients receive a GBSP
      at discharge, and this proportion would be further improved by improving the
      knowledge of dyslipidemia management guidelines among neurologists.

PMID- 24285961
TI  - Bedside evaluation of dizzy patients.
AB  - In recent decades there has been marked progress in the imaging and laboratory
      evaluation of dizzy patients. However, detailed history taking and comprehensive
      bedside neurotological evaluation remain crucial for a diagnosis of dizziness.
      Bedside neurotological evaluation should include examinations for ocular
      alignment, spontaneous and gaze-evoked nystagmus, the vestibulo-ocular reflex,
      saccades, smooth pursuit, and balance. In patients with acute spontaneous
      vertigo, negative head impulse test, direction-changing nystagmus, and skew
      deviation mostly indicate central vestibular disorders. In contrast, patients
      with unilateral peripheral deafferentation invariably have a positive head
      impulse test and mixed horizontal-torsional nystagmus beating away from the
      lesion side. Since suppression by visual fixation is the rule in peripheral
      nystagmus and is frequent even in central nystagmus, removal of visual fixation
      using Frenzel glasses is required for the proper evaluation of central as well as
      peripheral nystagmus. Head-shaking, cranial vibration, hyperventilation, pressure
      to the external auditory canal, and loud sounds may disclose underlying
      vestibular dysfunction by inducing nystagmus or modulating the spontaneous
      nystagmus. In patients with positional vertigo, the diagnosis can be made by
      determining patterns of the nystagmus induced during various positional maneuvers
      that include straight head hanging, the Dix-Hallpike maneuver, supine head roll,
      and head turning and bending while sitting. Abnormal smooth pursuit and saccades,
      and severe imbalance also indicate central pathologies. Physicians should be
      familiar with bedside neurotological examinations and be aware of the clinical
      implications of the findings when evaluating dizzy patients. 

PMID- 24285959
TI  - Oncogenic alternative splicing switches: role in cancer progression and prospects
      for therapy.
AB  - Alterations in the abundance or activities of alternative splicing regulators
      generate alternatively spliced variants that contribute to multiple aspects of
      tumor establishment, progression and resistance to therapeutic treatments.
      Notably, many cancer-associated genes are regulated through alternative splicing
      suggesting a significant role of this post-transcriptional regulatory mechanism
      in the production of oncogenes and tumor suppressors. Thus, the study of
      alternative splicing in cancer might provide a better understanding of the
      malignant transformation and identify novel pathways that are uniquely relevant
      to tumorigenesis. Understanding the molecular underpinnings of cancer-associated
      alternative splicing isoforms will not only help to explain many fundamental
      hallmarks of cancer, but will also offer unprecedented opportunities to improve
      the efficacy of anti-cancer treatments. 

PMID- 24285963
TI  - MRAS Genetic Variation Is Associated with Atherothrombotic Stroke in the Han
      Chinese Population.
AB  - BACKGROUND AND PURPOSE: Atherothrombotic cerebral infarction [atherothrombotic
      stroke (ATS)] shares common risk factors and pathophysiological mechanisms with
      coronary artery disease (CAD), and both diseases appear to have common
      susceptibility loci. The muscle RAS oncogene homolog gene (MRAS) has been
      identified as a susceptibility locus for CAD and is implicated in
      atherosclerosis. The aim of this study was to elucidate whether the single
      nucleotide polymorphisms (SNPs) and haplotypes of MRAS are associated with
      increased risk of ATS in a population of Han Chinese. METHODS: A case-controlled
      association study was conducted in which only patients with ATS (identified as a
      major subtype in the Korean modification of the Trial of Org 10172 in Acute
      Stroke Treatment classification) were enrolled. Subgroup analyses were carried
      out to determine whether the effect of the MRAS polymorphism was specific to age
      and gender among the subjects. RESULTS: In total, 194 ATS and 186 control
      subjects were included in the present study. Two tagging SNPs were identified in
      MRAS (rs40593 and rs3755751). A multivariate regression analysis revealed a
      positive association between rs40593 and ATS under dominant and additive models
      after adjustment for covariates. Subgroup analyses revealed that there were no
      gender differences with respect to allele or genotype frequencies between the
      groups. The AG genotype for rs40593 (p=0.028), the CT genotype for rs3755751
      (p=0.036), and G-allele carriers (AG plus GG) for rs40593 (p=0.015) exhibited a
      significant protective effect among those aged >=45 years. For the haplotype
      analysis, ATS subjects aged >=45 years had a higher frequency of the ACAC
      haplotype (76.0%) than the controls (68.1%; p<0.05); that haplotype was
      associated with an increased risk of ATS. CONCLUSIONS: The obtained data suggest
      a positive association between MRAS and ATS among the Han Chinese. Further
      studies should be performed with larger sample and among different ethnic
      populations, and gene-gene or gene-environment interactions should be considered.

PMID- 24285964
TI  - The response of carotid intima-media thickness to medical treatment is correlated
      with that of intracranial atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is
      considered as a major cause of stroke. The carotid intima-media thickness (CIMT),
      which accurately reflects the burden of generalized atherosclerosis, is also
      associated with stroke. The aim of this study was to determine the association
      between the CIMT and ICAS responses to medical treatment. METHODS: This study
      constituted part of the "Trial of cilostazol in symptomatic intracranial arterial
      stenosis"-2 that evaluated the ICAS response after randomized antiplatelet
      treatment. Magnetic resonance angiography and CIMT measurement were performed at
      baseline and after 7 months of treatment. CIMT was measured using semiautomated
      software, and was presented as maximum (CIMT-max) and average (CIMT-ave) values.
      The change in CIMT was compared relative to the ICAS response (i.e., progression,
      no-change, and regression). Ordinal logistic regression and analysis of
      covariance (ANCOVA) were used to analyze the association between the responses.
      RESULTS: Among the 101 enrolled patients, 85 underwent follow-up CIMT
      measurement. CIMT increased most in the ICAS progression group (CIMT-max: 0.09+/
      0.23, CIMT-ave: 0.04+/-0.12), and to a lesser degree in the no-change group (CIMT
      max: 0.02+/-0.16, CIMT-ave: 0.02+/-0.11), but decreased in patients with ICAS
      regression (CIMT-max: -0.04+/-0.11, CIMT-ave: -0.03+/-0.07; CIMT-max: p=0.010,
      CIMT-ave: p=0.015). Ordinal logistic regression analysis demonstrated that the
      change in CIMT-max was independently associated with the ICAS response (p=0.032).
      However, the ANCOVA revealed that the reverse was not true, in that the ICAS
      response was not independently associated with the change in CIMT after adjusting
      for confounding factors. CONCLUSIONS: The ICAS response may be associated with
      the CIMT response to medical treatment.

PMID- 24285965
TI  - The Efficacy of Exercise Programs for Parkinson's Disease: Tai Chi versus
      Combined Exercise.
AB  - BACKGROUND AND PURPOSE: Exercise is recommended for every patient with
      Parkinson's disease (PD). The effectiveness of two different forms of exercise
      for PD, Tai Chi and combined stretching-strengthening exercise, was compared.
      METHODS: Patients with mild-to-moderate PD were recruited to join either the
      combined stretching-strengthening exercise group (n=7), the Tai Chi group (n=9),
      or the control (nonintervention) group (n=7). Exercise was performed three times
      a week over a period of 8 weeks. The Tai Chi exercise was led by certified
      instructors based on a Tai-Chi-for-arthritis program. The combined stretching
      strengthening exercise comprised folk dancing, stepping, and elastic-band
      exercises. The subjects' functional fitness, parkinsonian symptoms, quality of
      life (QoL), and depression were evaluated. RESULTS: Both exercise groups yielded
      better results in their overall functional fitness after the intervention.
      However, no improvement with exercise was found for parkinsonian symptoms, as
      evaluated using the Unified Parkinson's Disease Rating Scale. With respect to the
      domains of QoL, the combined stretching-strengthening exercise group fared better
      in the social domain of QoL, and the Tai Chi group fared better in the emotional
      domain, while QoL and depression worsened in the control group. The
      postintervention QoL was improved relative to the control condition only for the
      Tai Chi group. Although the exercise interventions did not have any effect on
      depression, the control group was associated with a significant deterioration.
      CONCLUSIONS: Exercise improved the functional fitness and QoL of PD patients,
      with Tai Chi yielding better results in QoL and favorable results in functional
      fitness. These findings suggest that Tai Chi could be a good exercise strategy
      for patients with PD.

PMID- 24285966
TI  - Predictive Value of Somatosensory Evoked Potential Monitoring during Resection of
      Intraparenchymal and Intraventricular Tumors Using an Endoscopic Port.
AB  - BACKGROUND AND PURPOSE: Intraoperative neurophysiological monitoring (IONM) using
      upper and lower somatosensory evoked potentials (SSEPs) is an established
      technique used to predict and prevent neurologic injury during intracranial tumor
      resections. Endoscopic port surgery (EPS) is a minimally-invasive approach to
      deep intraparenchymal and intraventricular brain tumors. The authors intended to
      evaluate the predictive value of SSEP monitoring during resection of intracranial
      brain tumors using a parallel endoscopic technique. METHODS: A retrospective
      review was conducted of patients operated on from 2007-2010 utilizing IONM in
      whom endoscopic ports were used to remove either intraparenchymal or
      intraventricular tumors. Cases were eligible for review if an endoscopic port was
      used to resect an intracranial tumor and the electronic chart included all
      intraoperative monitoring data as well as pre- and post-operative neurologic
      exams. RESULTS: 139 EPS cases met criteria for inclusion. Eighty five patients
      (61%) had intraparenchymal and fifty four (39%) had intraventricular tumors or
      colloid cysts. SSEP changes were seen in eleven cases (7.9%), being irreversible
      in three (2.2%) and reversible in eight cases (5.8%). Seven patients (5.0%) with
      intraparenchymal tumors had SSEP changes which met our criterea for significant
      changes while there were four (2.9%) with intraventricular (p-value=0.25). Five
      patients suffered post operative deficits, two reversible and two irreversible
      SSEP changes. Only one case exhibited post operative hemiparesis with no SSEP
      changes. The positive predictive value of SSEP was 45.4% and the negative
      predictive value was 99.2%. CONCLUSIONS: Based on the high negative and low
      positive predictive values, the utility of SSEP monitoring for cylindrical port
      resections may be limited. However, the use of SSEP monitoring can be helpful in
      reducing the impact of endoscopic port manipulation when the tumor is closer to
      the somatosensory pathway.

PMID- 24285967
TI  - Contribution of Galvanic Vestibular Stimulation for the Diagnosis of HTLV-1
      Associated Myelopathy/Tropical Spastic Paraparesis.
AB  - BACKGROUND AND PURPOSE: Galvanic vestibular stimulation (GVS) is a low-cost and
      safe examination for testing the vestibulospinal pathway. Human T-lymphotropic
      virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is
      a slowly progressive disease that affects the vestibulospinal tract early in its
      course. This study compared the electromyographic (EMG) responses triggered by
      GVS of asymptomatic HTLV-1-infected subjects and subjects with HAM/TSP. METHODS:
      Bipolar galvanic stimuli (400 ms and 2 mA) were applied to the mastoid processes
      of 39 subjects (n=120 stimulations per subject, with 60 from each lower limb).
      Both the short latency (SL) and medium latency (ML) components of the EMG
      response were recorded from the soleus muscles of 13 healthy, HTLV-1-negative
      adults (56+/-5 years, mean+/-SD), and 26 individuals infected with HTLV-1, of
      whom 13 were asymptomatic (56+/-8 years) and 13 had HAM/TSP (60+/-6 years).
      RESULTS: The SL and ML EMG components were 55+/-4 and 112+/-10 ms, respectively,
      in the group of healthy subjects, 61+/-6 and 112+/-10 ms and in the HTLV-1
      asymptomatic group, and 67+/-8 and 130+/-3 ms in the HAM/TSP group (p=0.001). The
      SL component was delayed in 4/13 (31%) of the examinations in the HTLV-1
      asymptomatic group, while the ML component was normal in all of them. In the
      HAM/TSP group, the most common alteration was the absence of waves. CONCLUSIONS:
      A pattern of abnormal vestibular-evoked EMG responses was found in HTLV-1
      neurological disease, ranging from delayed latency among asymptomatic carriers to
      the absence of a response in HAM/TSP. GVS may contribute to the early diagnosis
      and monitoring of nontraumatic myelopathies.

PMID- 24285968
TI  - Early diagnosis and management of cerebral venous flow obstruction secondary to
      transsinus fracture after traumatic brain injury.
AB  - BACKGROUND AND PURPOSE: Cerebral venous flow obstruction (CVFO) is a fatal
      complication of traumatic brain injury. To compare the outcomes of patients with
      CVFO secondary to traumatic-brain-injury-induced transsinus fracture who were
      diagnosed early versus those diagnosed late in the therapeutic course. METHODS:
      In total, 403 patients with transsinus fracture were reviewed retrospectively.
      The patients were divided into an early-diagnosis group (n=338) and a delayed
      diagnosis group (n=65). The patients submitted to 2D time-of-flight magnetic
      resonance venography (2D-TOF MRV) and/or CT venography (CTV), depending upon the
      findings of intracranial pressure monitoring, in order to identify potentially
      complicated CVFO. These examinations took place within 3 days of the onset of
      malignant intracranial hypertension symptoms in the early-diagnosis group, and
      after an average of 7 days in the delayed-diagnosis group. Once diagnosed,
      patients received intravenous thrombolytic therapy with low-dose urokinase.
      Patients with massive transsinus epidural hematoma, depressed fracture, or
      cerebral hernia were treated surgically to relieve the compression and repair any
      damage to the venous sinuses. RESULTS: Cerebral venous flow obstruction was much
      more severe in the delayed-diagnosis group than in the early-diagnosis group
      (p<0.001), and hence patients in the former group were given a higher dose of
      urokinase (p<0.001) for thrombolytic therapy. They were also significantly more
      likely to need surgery (48.1% vs. 20.6%, p=0.003) and had a higher mortality rate
      (37.0% vs. 4.1%, p<0.001). However, patients in both groups experienced a
      similarly favorable prognosis, not only with regard to functional outcome but
      also with respect to neuroradiological improvement, as evaluated by 2D-TOF
      MRV/CTV at the final follow-up (p=0.218). CONCLUSIONS: Delayed diagnosis can
      result in increased risk of surgery and death in the acute phase. Thrombolytic
      therapy with low-dose urokinase resulted in promising improvements in both
      functional and neuroradiological outcomes in all of the patients in this study,
      regardless of the time to diagnosis.

PMID- 24285969
TI  - Impact of chronic simulated snoring on carotid atherosclerosis in rabbits.
AB  - BACKGROUND AND PURPOSE: Chronic simulated snoring was induced in rabbits to
      determine the impact of snoring on the development of atherosclerosis. METHODS:
      The pressure wave of induced snoring at the carotid bifurcation of rabbits was
      acquired by gently pressing the airway. This wave was then simulated using custom
      made mechanical devices. Twelve rabbits were used in this study, seven of which
      were assigned to the experimental group and the remaining five formed the control
      group. All of the rabbits were raised on a 1% high-cholesterol diet. Either
      working or sham devices were positioned at the ventral center of the neck in each
      rabbit. At the end of a 2-month observation period, all of the rabbits were
      sacrificed by perfusion fixation, the carotid arteries harvested, and the carotid
      atherosclerosis histology reviewed. RESULTS: All of the rabbits survived to the
      end of the experimental period. Blood sampling revealed the presence of
      hypercholesterolemia in both groups, with no significant difference between them.
      The presence and degree of atherosclerosis did not differ significantly between
      the groups. CONCLUSIONS: The findings of this study show the feasibility of
      making a chronic simulated snoring rabbit model. However, the causative role of
      snoring in carotid atherosclerosis was not detected in this animal study.

PMID- 24285970
TI  - Non-Ataxic Phenotypes of SCA8 Mimicking Amyotrophic Lateral Sclerosis and
      Parkinson Disease.
AB  - BACKGROUND: Spinocerebellar ataxia (SCA) type 8 (SCA8) is an inherited
      neurodegenerative disorder caused by the expansion of untranslated CTA/CTG
      triplet repeats on 13q21. The phenomenology of SCA8 is relatively varied when
      compared to the other types of SCAs and its spectrum is not well established.
      CASE REPORT: Two newly detected cases of SCA8 with the nonataxic phenotype and
      unusual clinical manifestations such as dopaminergic-treatment-responsive
      parkinsonism and amyotrophic lateral sclerosis (ALS) are described herein. Family
      A expressed good dopaminergic treatment-responsive parkinsonism as an initial
      manifestation and developed mild cerebellar ataxia with additional movements,
      including dystonic gait and unusual oscillatory movement of the trunk, during the
      disease course. The proband of family B presented as probable ALS with cerebellar
      atrophy on brain MRI, with a positive family history (a brother with typical
      cerebellar ataxia) and genetic confirmation for SCA8. CONCLUSIONS: Our findings
      support that the non-ataxic phenotypes could be caused by a mutation of the SCA8
      locus which might affect neurons other than the cerebellum.

PMID- 24285971
TI  - A Case of GNE Myopathy Presenting a Rapid Deterioration during Pregnancy.
AB  - BACKGROUND: GNE myopathy is characterized by early-adult-onset distal myopathy
      sparing quadriceps caused by mutations in the GNE gene encoding UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, an enzyme in the sialic
      acid synthesis pathway. CASE REPORT: A 27-year-old Korean woman presented a rapid
      deterioration in strength of the distal lower limbs during her first pregnancy.
      She was diagnosed with GNE myopathy and carrying the compound heterozygous
      mutations of the GNE gene (D208N/M29T). CONCLUSIONS: This is a representative
      case implying that an increased requirement of sialic acid during pregnancy might
      trigger a clinical worsening of GNE myopathy.

PMID- 24285972
TI  - Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without
      Optic Atrophy.
AB  - BACKGROUND: X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by
      mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1).
      There has been only one case report of CMTX5 patients. The aim of this study was
      to identify the causative gene in a family with CMTX with peripheral neuropathy
      and deafness. CASE REPORT: A Korean family with X-linked recessive CMT was
      enrolled. The age at the onset of hearing loss of the male proband was 5 months,
      and that of steppage gait was 6 years; he underwent cochlear surgery at the age
      of 12 years. In contrast to what was reported for the first patients with CMTX5,
      this patient did not exhibit optic atrophy. Furthermore, there was no cognitive
      impairment, respiratory dysfunction, or visual disturbance. Assessment of his
      family history revealed two male relatives with very similar clinical
      manifestations. Electrophysiological evaluations disclosed sensorineural hearing
      loss and peripheral neuropathy. Whole-exome sequencing identified a novel
      p.Ala121Gly (c.362C>G) PRPS1 mutation as the underlying genetic cause of the
      clinical phenotype. CONCLUSIONS: A novel mutation of PRPS1 was identified in a
      CMTX5 family in which the proband had a phenotype of peripheral neuropathy with
      early-onset hearing loss, but no optic atrophy. The findings of this study will
      expand the clinical spectrum of X-linked recessive CMT and will be useful for the
      molecular diagnosis of clinically heterogeneous peripheral neuropathies.

PMID- 24285974
TI  - Altered immune regulation in type 1 diabetes.
AB  - Research in genetics and immunology was going on separate strands for a long
      time. Type 1 diabetes mellitus might not be characterized with a single
      pathogenetic factor. It develops when a susceptible individual is exposed to
      potential triggers in a given sequence and timeframe that eventually disarranges
      the fine-tuned immune mechanisms that keep autoimmunity under control in health.
      Genomewide association studies have helped to understand the congenital
      susceptibility, and hand-in-hand with the immunological research novel paths of
      immune dysregulation were described in central tolerance, apoptotic pathways, or
      peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are
      contributing to the immune dysregulation. The interplay between genetic
      susceptibility and potential triggers is likely to play a role at a very early
      age and gradually results in the loss of balanced autotolerance and subsequently
      in the development of the clinical disease. Genetic susceptibility, the impaired
      elimination of apoptotic beta -cell remnants, altered immune regulatory
      functions, and environmental factors such as viral infections determine the
      outcome. Autoreactivity might exist under physiologic conditions and when the
      integrity of the complex regulatory process is damaged the disease might develop.
      We summarized the immune regulatory mechanisms that might have a crucial role in
      disease pathology and development. 

PMID- 24285976
TI  - The Evaluation of the Body Weight Lowering Effects of Herbal Extract THI on
      Exercising Healthy Overweight Humans: A Randomized Double-Blind, Placebo
      Controlled Trial.
AB  - We investigated the effects of herbal extracts, a mixture of Scutellariae Radix
      and Platycodi Radix containing the active ingredients Baicalin and Saponin
      (target herbal ingredient (THI)), on lowering body weight. The present study was
      a prospective, randomized, double-blind, and placebo-controlled trial carried out
      at the outpatient department of a hospital over a period of 2 months. Group 1
      patients (n = 30) received THI, and group 2 patients (n = 23) received placebo
      three times a day before meals. Weight, waist circumference, BMI, total
      cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and glucose were
      measured at baseline and again at the 2nd month. For safety evaluation, various
      hematological and biochemical parameters were assessed. Values of mean change of
      weight in the THI-treated group were -1.16 +/- 1.41 kg and in the placebo-treated
      group were -0.24 +/- 1.70 kg, respectively. The difference in mean change of
      weight in the THI-treated group compared with that in the placebo-treated group
      was statistically significant (P < 0.05). The incidence of subjective and
      objective adverse drug reactions was insignificant (P > 0.05). THI was
      statistically significant in its effectiveness on the weight loss. 

PMID- 24285975
TI  - A survey of chinese medicinal herbal treatment for chemotherapy-induced oral
      mucositis.
AB  - Oral mucositis is one of the common side effects of chemotherapy treatment with
      potentially severe implications. Despite several treatment approaches by
      conventional and complementary western medicine, the therapeutic outcome is often
      not satisfactory. Traditional Chinese Medicine (TCM) offers empirical herbal
      formulas for the treatment of oral ulceration which are used in adaptation to
      chemotherapy-induced mucositis. While standard concepts for TCM treatment do not
      exist and acceptance by conventional oncologists is still low, we conducted a
      review to examine the evidence of Chinese herbal treatment in oral mucositis.
      Eighteen relevant studies on 4 single herbs, 2 combinations of 2 herbs, and 11
      multiherbal prescriptions involving 3 or more compounds were included.
      Corresponding molecular mechanisms were investigated. The knowledge about
      detailed herbal mechanisms, especially in multi-herbal prescriptions is still
      limited. The quality of clinical trials needs further improvement. Meta-analysis
      on the existent database is not possible but molecular findings on Chinese
      medicinal herbs indicate that further research is still promising for the
      treatment of chemotherapy-induced oral mucositis. 

PMID- 24285977
TI  - Hinokitiol, a natural tropolone derivative, offers neuroprotection from
      thromboembolic stroke in vivo.
AB  - Hinokitiol ( beta -thujaplicin), a tropolone-related compound found in the
      heartwood cupressaceous plants, is widely used in hair tonics, tooth pastes,
      cosmetics, and food as an antimicrobial agent. Increasing evidence has confirmed
      that hinokitiol exhibits anticancer activity in a variety of cancers through
      inhibition of cell proliferation. In the present study, we have investigated the
      neuroprotective effect and mechanisms of hinokitiol in rats against middle
      cerebral artery occlusion (MCAO)-induced thromboembolic stroke. Treatment with
      hinokitiol (0.2 and 0.5 mg/kg; intraperitoneally) 30 min before MCAO dose
      dependently attenuated cerebral ischemia and improved neurobehavioral deficits in
      cerebral ischemic rats. Intraperitoneal administration of hinokitiol
      significantly reduced infarct size compared to that in control rats. MCAO-induced
      focal cerebral ischemia was associated with increased expressions of hypoxia
      inducible factor (HIF)-1 alpha , inducible nitric oxide synthase (iNOS), tumor
      necrosis factor (TNF)- alpha , and active caspase-3 in ischemic regions. However,
      these expressions were obviously inhibited by hinokitiol (0.2 and 0.5 mg/kg)
      treatment. This study demonstrates for the first time that in addition to being
      originally considered as an agent against microbes and variety of cancers,
      hinokitiol possesses potent neuroprotective activity. This activity is mediated,
      at least in part, by inhibition of inflammatory responses (i.e., HIF-1 alpha ,
      iNOS expression) and apoptosis (i.e., TNF- alpha , active caspase-3), resulting
      in a reduction of infarct volume and improvement in neurobehavior in rats with
      cerebral ischemia. Therefore, the therapeutic potential of hinokitiol may lead to
      novel role for treatment or prevention of ischemia/reperfusion injury-related
      disorders. 

PMID- 24285978
TI  - Pistacia atlantica Resin Has a Dose-Dependent Effect on Angiogenesis and Skin
      Burn Wound Healing in Rat.
AB  - Objectives. The aim of the present study was to evaluate the effect of Pistacia
      atlantica resin extract on the rat skin burn wound healing. Methods. Thirty-two
      Wistar rats were divided into four groups and treated by vehicle, 5%, 10%, and
      20% concentration of Pistacia atlantica resin extract for 14 days (G1, G2, G3,
      and G4, resp.). The efficacy of treatment was assessed based on reduction of burn
      wound size and histological and molecular characteristics. Results. alpha -Pinene
      (46.57%) was the main content of essential oil of resin. There were no
      statistically significant differences between groups according to wound size
      analysis. The mean histological wound healing scores were not statistically
      different. Capillary counts of G2 and G3 were significantly higher than those of
      the G1 (P = 0.042 and 0.032, resp.). NO concentration in wound fluids on the 5th
      day of study was not significantly different between groups (P = 0.468). But bFGF
      concentration in G2 and G3 and PDGF concentration in G3 were significantly higher
      in comparison to G1 (P = 0.043, 0.017, and 0.019, resp.). Conclusion. Our results
      revealed that Pistacia atlantica resin extract has a concentration-dependent
      effect on the healing of burn wounds after 14 days of treatment by increasing the
      concentration of bFGF and PDGF and also through improving the angiogenesis. 

PMID- 24285979
TI  - Pomegranate: its health and biomedical potential.

PMID- 24285980
TI  - NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with
      Advanced Solid Tumors.
AB  - PURPOSE: European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly
      used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and
      mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and
      maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3)
      formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma
      concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. METHODS: 
      DESIGN: increasing mistletoe and fixed GEM dose in stage I and increasing doses
      of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT)
      were grade (G) 3 nonhematologic and G4 hematologic events related to platelets
      and granulocytes only [corrected]; MTD was reached with 2 DLTs in one dosage
      level. Response in stage IV ASC was assessed with descriptive statistics.
      Statistical analyses examined clinical response/survival and ANC recovery.
      RESULTS: DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure,
      and G3 cellulitis, attributed to mistletoe. GEM 1300 mg/m(2) [corrected] and
      mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed
      nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected
      by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to
      increase between baseline and cycle 2 in stage I dose escalation. 6% of patients
      showed partial response, 42% stable disease. Median survival was 200 days.
      Compliance with mistletoe injections was high. CONCLUSION: GEM plus mistletoe is
      well tolerated. No botanical/drug interactions were observed. Clinical response
      is similar to GEM alone.

PMID- 24285981
TI  - Versatile tuning of supramolecular hydrogels through metal complexation of
      oxidation-resistant catechol-inspired ligands.
AB  - The mussel byssal cuticle employs DOPA-Fe3+ complexation to provide strong, yet
      reversible crosslinking. Synthetic constructs employing this design motif based
      on catechol units are plagued by oxidation-driven degradation of the catechol
      units and the requirement for highly alkaline pH conditions leading to decreased
      performance and loss of supramolecular properties. Herein, a platform based on a
      4-arm poly(ethylene glycol) hydrogel system is used to explore the utility of
      DOPA analogues such as the parent catechol and derivatives, 4-nitrocatechol
      (nCat) and 3-hydroxy-4-pyridinonone (HOPO), as structural crosslinking agents
      upon complexation with metal ions. HOPO moieties are found to hold particular
      promise, as robust gelation with Fe3+ occurs at physiological pH and is found to
      be largely resistant to oxidative degradation. Gelation is also shown to be
      triggered by other biorelevant metal ions such as Al3+, Ga3+ and Cu2+ which
      allows for tuning of the release and dissolution profiles with potential
      application as injectable delivery systems.

PMID- 24285982
TI  - Trauma- and stressor related disorders in the tuareg refugees of a cAMP in
      burkina faso.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is reported to be common among
      refugees. We set out to explore risk of Trauma- and Stress-or-Related Disorders
      and the associated burden of psychological distress in a refugee camp of Malian
      Refugees in Burkina Faso. METHODS: One out of five persons living in the camp was
      selected randomly and interviewed using the French version of the Short Screening
      Scale for PTSD and the validated K6 scale to measure psychiatric morbidity.
      RESULTS: Around 60% of the interviewed sample (N=408) met the criteria for Trauma
      and Stress-or-Related Disorders and also reported severe mental distress on K6
      scores. Women aged 40 and over were found to be at higher risk of Trauma- and
      Stress-or-Related Disorders whereas young people (39 or younger) scored higher on
      K6 ratings. Around 83% of the surveyed subjects had a family member killed in the
      war, 91% a relative in the war, more than 80% had a family member suffering from
      physical injuries, and 90% reported problems with food and housing. The frequency
      of these life events was not surprisingly higher in persons with Trauma- and
      Stress-or-Related Disorders, with the death of a family member and severe
      problems with food being specifically related to them. CONCLUSION: These results
      point to important psychological suffering in a population that is often ignored
      by the media and international political authorities. Immediate steps are
      required to provide urgent legal and humanitarian protection to those who are
      forced to flee their homes and cross international borders because of disasters.

PMID- 24285983
TI  - Developing Privacy Solutions for Sharing and Analyzing Healthcare Data.
AB  - The extensive use of electronic health data has increased privacy concerns. While
      most healthcare organizations are conscientious in protecting their data in their
      databases, very few organizations take enough precautions to protect data that is
      shared with third party organizations. Recently the regulatory environment has
      tightened the laws to enforce privacy protection. The goal of this research is to
      explore the application of data masking solutions for protecting patient privacy
      when data is shared with external organizations for research, analysis and other
      similar purposes. Specifically, this research project develops a system that
      protects data without removing sensitive attributes. Our application allows high
      quality data analysis with the masked data. Dataset-level properties and
      statistics remain approximately the same after data masking; however, individual
      record-level values are altered to prevent privacy disclosure. A pilot evaluation
      study on large real-world healthcare data shows the effectiveness of our solution
      in privacy protection.

PMID- 24285984
TI  - Privacy-preserving health data collection for preschool children.
AB  - With the development of network technology, more and more data are transmitted
      over the network and privacy issues have become a research focus. In this paper,
      we study the privacy in health data collection of preschool children and present
      a new identity-based encryption protocol for privacy protection. The background
      of the protocol is as follows. A physical examination for preschool children is
      needed every year out of consideration for the children's health. After the
      examination, data are transmitted through the Internet to the education
      authorities for analysis. In the process of data collection, it is unnecessary
      for the education authorities to know the identities of the children. Based on
      this, we designed a privacy-preserving protocol, which delinks the children's
      identities from the examination data. Thus, the privacy of the children is
      preserved during data collection. We present the protocol in detail and prove the
      correctness of the protocol. 

PMID- 24285986
TI  - A keratocyst in the buccal mucosa with the features of keratocystic odontogenic
      tumor.
AB  - A 74-year-old male patient consulted us for an elastic firm mass in the right
      buccal mucosa. CT examination revealed a well-circumscribed oval cystic lesion in
      the anterior region of the masseter muscle. On MRI, the lesion showed a low
      signal on T1-weighted image and a high signal on T2-weighted image. Aspiration
      biopsy demonstrated the presence of squamous cells in whitish liquid. Under the
      diagnosis of epidermoid cyst, the lesion was intraorally extirpated under general
      anesthesia. The lesion was cystic at the size of 30 * 25mm. Histologically, the
      cyst wall was lined with parakeratinized squamous epithelium corrugated on its
      surface, the basal layer of which consisted of cuboidal cells showing palisading
      of the nuclei. Immunohistochemically, the lining epithelium was positive for CK17
      and negative for CK10. The basal and suprabasal cells were labeled for Ki-67 at a
      relatively high rate. These features are compatible with those of keratocystic
      odontogenic tumor. 

PMID- 24285985
TI  - Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of
      Glial Lineage.
AB  - Glial tumors have demonstrated abilities to sustain growth via recruitment of
      glial progenitor cells (GPCs), which is believed to be driven by chemotactic
      cues. Previous studies have illustrated that mouse GPCs of different genetic
      backgrounds are able to replicate the dispersion pattern seen in the human
      disease. How GPCs with genetic backgrounds transformed by tumor paracrine
      signaling respond to extracellular cues via migration is largely unexplored, and
      remains a limiting factor in utilizing GPCs as therapeutic targets. In this
      study, we utilized a microfluidic device to examine the chemotaxis of three
      genetically-altered mouse GPC populations towards tumor conditioned media, as
      well as towards three growth factors known to initiate the chemotaxis of cells
      excised from glial tumors: Hepatocyte Growth Factor (HGF), Platelet-Derived
      Growth Factor-BB (PDGF-BB), and Transforming Growth Factor-alpha (TGF-alpha). Our
      results illustrate that GPC types studied exhibited chemoattraction and
      chemorepulsion by different concentrations of the same ligand, as well as
      enhanced migration in the presence of ultra-low ligand concentrations within
      environments of high concentration gradient. These findings contribute towards
      our understanding of the causative and supportive roles that GPCs play in tumor
      growth and reoccurrence, and also point to GPCs as potential therapeutic targets
      for glioma treatment.

PMID- 24285987
TI  - Quality of life in patients with knee osteoarthritis: a commentary on nonsurgical
      and surgical treatments.
AB  - Knee osteoarthritis (OA) has a significant negative impact on health-related
      quality of life (HRQoL). Identification of therapies that improve HRQoL in
      patients with knee OA may mitigate the clinical, economic, and social burden of
      this disease. The purpose of this commentary is to report the impact of knee OA
      on HRQoL, describe the change in HRQoL attributable to common knee OA
      interventions, and summarize findings from clinical trials of a promising
      therapy. Nonsurgical therapies do not reliably modify HRQoL in knee OA patients
      given their general inability to alleviate physical manifestations of OA.
      Surgical knee OA interventions generally result in good to excellent patient
      outcomes. However, there are significant barriers to considering surgery, which
      limits clinical utility. Therapies that most effectively control OA-related pain
      with a low risk: benefit ratio will likely have the greatest benefit on HRQoL
      with greater rates of patient adoption. Initial clinical trial findings suggest
      that less invasive joint unloading implants hold promise in bridging the
      therapeutic gap between nonsurgical and surgical treatments for the knee OA
      patient. 

PMID- 24285988
TI  - In vitro elution characteristics of gentamicin and vancomycin from synthetic bone
      graft substitutes.
AB  - OBJECTS: Beta tricalciumphosphate pellets loaded with individualized antibiotics
      may represent novel options in the treatment of osteomyelitis and infectious bone
      disease. Here, the in vitro antibiotic elution of vancomycin and gentamicin from
      the synthetic bone graft substitutes Cerasorb((r)) and Cerasorb M((r)) was
      tested. METHODS: Antibiotic elution and concentration of gentamcin and vancomycin
      were measured using photometrically-based measurement and homogeneous particle
      enhanced turbidimetric inhibition immunoassays (PETINIA). RESULTS: Initially both
      materials showed a high release of the loaded antibiotics, with Cerasorb M((r))
      showing lower release levels for gentamicin and vancomycin than Cerasorb((r)).
      Gentamicin concentrations of Cerasorb M granules and Cerasorb were below the
      minimum detectiontreshold until day four and six of the experiment respectively.
      The vancomycin release-level followed a similar pattern, although the vancomycin
      concentration eluted by Cerasorb M((r)) granules stayed above the detection
      threshold during the experimental time. CONCLUSIONS: Cerasorb((r)) and Cersorb
      M((r)) may represent a new treatment option in osteomyelitis and infectious bone
      disease.

PMID- 24285989
TI  - Intrarater and interrater reliability of the socket version marker in total hip
      replacement.
AB  - The aim of this study was to evaluate the intraobserver and interobserver
      variability in determining the socket version using the wire marker. 100
      anteroposterior pelvis radiographs of cemented primary total hip replacements
      were reviewed by two orthopaedic consultants and registrars, twice. Intrarater
      and interrater reliability were assessed using Cohen's kappa. Intrarater kappas
      for junior doctors were 0.78 and 0.80, 0.73 and 0.62 for Consultants. Interrater
      kappas were 0.60 between the two Consultants and 0.63 between the two Junior
      Doctors. The kappas between Consultant A and Junior Doctor A was 0.61, between
      Consultant A and Junior Doctor B was 0.59, between Consultant B and Junior Doctor
      A was 0.53 and between Consultant B and Junior Doctor B was 0.46. Intrarater
      reliability was substantial for the two junior doctors and the two consultants.
      Interrater reliability was moderate-to-substantial between the two consultants,
      between the two junior doctors and between each pair of junior
      doctors/consultants. 

PMID- 24285990
TI  - Flow manipulation and cell immobilization for biochemical applications using
      thermally responsive fluids.
AB  - A flow redirection and single cell immobilization method in a microfluidic chip
      is presented. Microheaters generated localized heating and induced poly(N
      isopropylacrylamide) phase transition, creating a hydrogel that blocked a channel
      or immobilized a single cell. The heaters were activated in sets to redirect flow
      and exchange the fluid in which an immobilized cell was immersed. A yeast cell
      was immobilized in hydrogel and a 4',6-diamidino-2-phenylindole (DAPI)
      fluorescent stain was introduced using flow redirection. DAPI diffused through
      the hydrogel and fluorescently labelled the yeast DNA, demonstrating in situ
      single cell biochemistry by means of immobilization and fluid exchange. 

PMID- 24285991
TI  - Acute bioenergetic intervention or pharmacological preconditioning protects
      neuron against ischemic injury.
AB  - Although acute ischemic stroke has high mortality and morbidity rate but yet
      still has very limited treatment. In this study we have tested the concept of
      neuron protection by acute bioenergetic intervention or by pharmacological
      preconditioning with natural antioxidants. Adenosine triphosphate (ATP),
      pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used
      as bioenergy stabilizer. We induced ATP depletion model by incubating cells with
      media added with ATP-depleting agents for 2 hours. Treatment with bioenergy
      stabilizer started 10-min post inducing of ATP-depletion. The acute treatment
      with bioenergy stabilizer significantly increased cell viability in neuro-2a
      cells. In searching for a pharmacological preconditioning candidate for reducing
      ischemic injury, we tested cocoa-derived flavanols using bilateral common carotid
      artery occlusion (BCCAO). We pretreated mice with cocoa-derived flavanols (75
      mg/kg) or water orally for 7 days and subjected mice for 12 minutes BCCAO. At 7
      days post-ischemia, the number of surviving hippocampal CA1 neurons was
      significantly higher in the treated mice than in the water-treated controls. The
      protection from cocoa-derived flavanols was found associated with increased total
      antioxidant capacity in the brain. Our results indicate that for reducing acute
      ischemic injury bioenergetic intervention using advanced drug delivery tools is
      conceptually feasible, and for reducing reperfusion related secondary injury
      pharmacological preconditioning may provide significant protection.

PMID- 24285992
TI  - Nrf2 in host defense: over the rainbow.

PMID- 24285993
TI  - US Editors and Reviewers can no Longer Handle Submissions by Authors Employed by
      the Government of Iran: Is it Fair and Logical?

PMID- 24285994
TI  - Cloning, Expression and Purification of Penicillin Binding Protein2a (PBP2a) from
      Methicillin Resistant Staphylococcus aureus: A Study on Immunoreactivity in
      Balb/C Mouse.
AB  - BACKGROUND: Staphylococcus aureus (S. aureus) is a major nosocomial pathogen and
      the infection with this organism in human is increasing due to the spread of
      antibiotic resistant strains. One of the resistance mechanisms of S. aureus
      comprises modification in binding proteins to penicillin. Vaccine strategy may be
      useful in controlling the infections induced by this organism. This study aimed
      at developing and producing the recombinant protein PBP2a as a vaccine candidate
      and evaluating the related humoral immune response in a murine model. METHODS: A
      242 bp fragment of mecA gene was amplified by PCR from S. aureus COL strain and
      then cloned into prokaryotic expression vector pET-24a. For expression of
      recombinant protein, pET24a-mec plasmid was transformed into competent E. coli
      BL21 (DE3) cells. Recombinant protein was over expressed with 1 mM isopropythio
      beta-D-galctoside (IPTG) and purified using Ni-NTA agarose. SDS-PAGE and western
      blotting were carried out to confirm protein expression. For immunization of
      experimental groups, Balb/c mice were injected subcutaneously with 20 ug of
      recombinant PBP2a three times with three weeks intervals. The sera of
      experimental groups were collected three weeks after the last immunization and
      then specific antibodies were evaluated by ELISA method. RESULTS: Successful
      cloning of mecA was confirmed by colony-PCR, enzymatic digestion, and sequencing.
      SDS-PAGE and western blot analysis showed that recombinant protein with molecular
      weight of 13 kDa is over expressed. In addition, high titer of specific antibody
      against PBP2a in vaccinated mice was developed as compared with the control group
      and confirmed the immunogenicity of the vaccine candidate. CONCLUSION: Results
      suggest that PBP2a recombinant induced specific antibodies and can be used as
      Staphylococcal vaccine candidate after further studies.

PMID- 24285995
TI  - Production and characterization of a murine monoclonal antibody against human
      ferritin.
AB  - BACKGROUND: Ferritin is an iron storage protein, which plays a key role in iron
      metabolism. Measurement of ferritin level in serum is one of the most useful
      indicators of iron status and also a sensitive measurement of iron deficiency.
      Monoclonal antibodies may be useful as a tool in various aspects of ferritin
      investigations. In this paper, the production of a murine monoclonal antibody
      (mAb) against human ferritin was reported. METHODS: Balb/c mice were immunized
      with purified human ferritin and splenocytes of hyper immunized mice were fused
      with Sp2/0 myeloma cells. After four times of cloning by limiting dilution, a
      positive hybridoma (clone: 2F9-C9) was selected by ELISA using human ferritin.
      Anti-ferritin mAb was purified from culture supernatants by affinity
      chromatography. RESULTS: Determination of the antibody affinity for ferritin by
      ELISA revealed a relatively high affinity (2.34*10(9) M (-1)) and the isotype was
      determined to be IgG2a. The anti-ferritin mAb 2F9-C9 reacted with 79.4% of Hela
      cells in flow cytometry. The antibody detected a band of 20 kDa in K562 cells,
      murine and human liver lysates, purified ferritin in Western blot and also
      ferritin in human serum. CONCLUSION: This mAb can specifically recognize ferritin
      and may serve as a component of ferritin diagnostic kit if other requirements of
      the kit are met.

PMID- 24285996
TI  - Production and characterization of recombinant light chain and carboxyterminal
      heavy chain fragments of tetanus toxin.
AB  - BACKGROUND: Light chain (LC) and heavy chain carboxyterminal subdomain (HCC)
      fragments are the most important parts of tetanus neurotoxin (TeNT) which play
      key roles in toxicity and binding of TeNT, respectively. In the present study,
      these two fragments were cloned and expressed in a prokaryotic system and their
      identity was confirmed using anti-TeNT specific polyclonal and monoclonal
      antibodies. METHODS: LC and HCC gene segments were amplified from Clostridium
      tetani genomic DNA by PCR, cloned into pET28b(+) cloning vector and transformed
      in Escherichia coli (E. coli) BL21(DE3) expression host. Recombinant proteins
      were then purified through His-tag using Nickel-based chromatography and
      characterized by SDS-PAGE, Western blotting and ELISA techniques. RESULTS:
      Recombinant light chain and HCC fragments were successfully cloned and expressed
      in (E. coli) BL21 (DE3). Optimization of the induction protocol resulted in
      production of high levels of HCC (~35% of total bacterial protein) and to lesser
      extends of LC (~5%). Reactivity of the His-tag purified proteins with specific
      polyclonal and monoclonal antibodies confirmed their renatured structure and
      identity. CONCLUSION: Our results indicate successful cloning and production of
      recombinant LC and HCC fragments of TeNT. These two recombinant proteins are
      potentially useful tools for screening and monitoring of anti-TeNT antibody
      response and vaccine production.

PMID- 24285997
TI  - Expression and Purification of Recombinant ROP1 of Toxoplasma gondii in Bacteria.
AB  - BACKGROUND: Toxoplasmosis is a worldwide-distributed infection which is mostly
      asymptomatic but can cause serious health problems in congenitally-infected
      newborns and immunecompromised individuals. Research is undergoing both to
      improve Toxoplasma serological tests, which play the main role in laboratory
      diagnosis of the infection, and develop an effective vaccine to prevent the
      infection. Some studies showed usefulness of rhoptry protein 1 (ROP1) antigen of
      Toxoplasma gondii (T. gondii) in serodiagnosis of the infection and induction of
      protective immunity. The purpose of this study was to produce recombinant ROP1
      and evaluate its antigenicity against human infected sera. METHODS: DNA encoding
      ROP1, amino acids 171 to 574, was obtained from T. gondii RH strain by polymerase
      chain reaction amplification and cloned in prokaryotic expression plasmid pET
      15b. rROP1 was expressed in Escherichia coli (E. coli) and purified in a single
      step by immobilized metal ion affinity chromatography. RESULTS: DNA sequencing
      showed 99% similarity between the cloned sequence and the corresponding sequence
      in Gene bank. Results indicated the proper antigenicity of rROP1. Sera from
      Toxoplasma infected individuals specifically recognized rROP1 in Western
      blotting. CONCLUSION: rROP1 is antigenic toward human infected sera and can be
      used in studies for development of both a Toxoplasma serological test and a
      protective vaccine.

PMID- 24285998
TI  - Micropatterning of ECM Proteins on Glass Substrates to Regulate Cell Attachment
      and Proliferation.
AB  - BACKGROUND: Micropatterning is becoming a powerful tool for studying cells in
      vitro. This method not only uses very small amount of material but also mimic the
      microenvironment structure present in living tissues better than flask culturing
      techniques. In previous studies using micropatterning of extracellular matrix
      proteins on glass surfaces, the rate of protein detachment from the surface was
      so high that the proteins and the cultivated cells detached after 3 three days of
      cell seeding. METHODS: Here we optimized the glass surface modification method to
      fulfill the requirement of most in vitro studies. RESULTS: In our study we showed
      that the optimum time for glass surface modification reaction is 1.5 hr, and the
      cells could be tracked in vitro for over 15 days after cell seeding which is
      enough for the most in vitro studies. As a model, we cultivated HEK 293T and
      HepG2 cells on the collagen micro-patterns and showed that they have normal
      growth and morphology on these micropatterns. The HEK cells also transfected with
      pmaxGFP plasmid vector to show that the cells on collagen micropatterns could
      also used in transfection studies. CONCLUSION: Taking these together, this novel
      method is promising for efficient cell culture studies on micropatterened
      surfaces in the future.

PMID- 24285999
TI  - Development of polymer-coated glass slides as optical oligonucleotide
      microarrays.
AB  - BACKGROUND: The microarray technology is in needed of cost-effective, low
      background noise and stable substrates for successful hybridization and analysis.
      METHODS: In this research, we developed a three-dimentional stable and
      mechanically reliable microarray substrates by coating of two polymeric layers on
      standard microscope glass slides. For fabrication of these substrates, a thin
      film of oxidized agarose was prepared on the Poly-L-Lysine (PLL) coated glass
      slides. Unmodified oligonucleotide probes were spotted and immobilized on these
      double layered thin films by adsorption on the porous structure of the agarose
      film. Some of the aldehyde groups of the activated agarose linked covalently to
      PLL amine groups; on the other side, they bound to amino groups of adsorbed tail
      of biomolecules. These linkages were fixed by UV irradiation at 254 nm using a CL
      1000 UV. These prepared substrates were compared to only agarose-coated and PLL
      coated slides. RESULTS: Atomic Force Microscope (AFM) results demonstrated that
      agarose provided three-dimensional surface which had higher loading and bindig
      capacity for biomolecules than PLL-coated surface which had two-dimensional
      surface. The nano-indentation tests demonstrated the prepared double coating was
      more reliable and flexible for mechanical robotic spotting. In addition, the
      repeated indentation on different substrates showed uniformity of coatings. The
      stability of novel coating was sufficient for hybridization process. The signal
      to-noise ratio in hybridization reactions performed on the agarose-PLL coated
      substrates increased two fold and four fold compared to agarose and PLL coated
      substrates, respectively. CONCLUSION: Finally, the agarose-PLL microarrays had
      the highest signal (2920) and lowest background signal (205) in hybridization,
      suggesting that the prepared slides are suitable in analyzing wide concentration
      range of analytes.

PMID- 24286001
TI  - Retracted: Genotyping analysis of circulating fetal cells reveals high frequency
      of vanishing twin following transfer of multiple embryos.

PMID- 24286000
TI  - Mutation Analysis of SLC20A2 and SPP2 as Candidate Genes for Familial Idiopathic
      Basal Ganglia Calcification.
AB  - BACKGROUND: Familial Idiopathic Basal Ganglia Calcification (IBGC) is a rare
      neurodegenerative disorder which is usually transmitted as an autosomal dominant
      trait. IBGC is genetically heterogeneous and SLC20A2, on chromosome 8p21.1
      8q11.23, is the first gene found in IBGC-affected patients with varied ancestry.
      On the other hand, several candidate genes for IBGC on chromosome 2q37, including
      the SPP2 gene, may play a role in inhibiting calcification. METHODS: Totally, 22
      members of a three generational Iranian family affected by IBGC, with an
      autosomal dominant pattern of inheritance were included in this study. DNA was
      extracted from the whole blood using standard salting out method. To find a
      mutation responsible for IBGC, we sequenced the coding region of SLC20A2 as well
      as promoter and coding region of SPP2 in the index subject of IBGC-affected
      family. RESULTS: Pathogenic mutation was found neither in SLC20A2 nor in SPP2.
      CONCLUSION: Our results strengthen genetic heterogeneity of this condition.
      Additional mutation studies are necessary to find a gene or genes responsible for
      IBGC in this affected family.

PMID- 24286004
TI  - Whole body vibration therapy in AIS: further research needed.

PMID- 24286002
TI  - The utility of focus group interviews to capture dietary consumption data in the
      distant past: dairy consumption in Kazakhstan villages 50 years ago.
AB  - From 1949 to 1962, residents of several villages in Kazakhstan received
      substantial doses of radiation to the thyroid gland resulting from nuclear tests
      conducted at the Semipalatinsk Nuclear Test Site. The primary source of radiation
      was internal from an intake of radioactive iodine by consumption of contaminated
      dairy products. A previous research study of childhood exposure and thyroid
      disease in this region gathered limited data on study participants' dairy intake
      at the time of the fallout for the purpose of estimating past radiation doses. As
      many participants were too young at the time of the nuclear tests to recall
      dietary consumption and existing sources of archival data are limited, it was
      necessary to interview parents and other village residents who cared for children
      during this time - older adults ranging in age from 75 to 90 years. Results from
      11 focus group interviews conducted in 2007 with 82 women from 4 villages in
      Kazakhstan yielded group-level estimates of age-, gender-, ethnicity- and village
      specific dairy consumption patterns in rural Kazakhstan during the 1950s.
      Children typically consumed cow's milk with limited consumption of mare, goat and
      sheep milk; and consumed dairy products such as sour milk (airan), soft cottage
      cheese (tvorog) and fermented mare milk (koumiss) with the greatest amounts of
      koumiss reported at ages 15-21 years. The consumption patterns differed by age,
      and between Kazakh and Russian children, which should lead to different estimates
      of radiation exposure to the thyroid. This study showed the utility of focus
      groups to obtain quantitative estimates for dietary intake in the distant past. 

PMID- 24286005
TI  - Surgical intervention successful for BP-related incomplete fractures.

PMID- 24286003
TI  - Current approaches to the initial treatment of symptomatic multiple myeloma.
AB  - The treatment of newly diagnosed multiple myeloma has dramatically changed since
      the emergence of proteasome inhibitors and immunomodulatory drugs. Front-line
      combination regimens incorporating novel drugs such as thalidomide, bortezomib
      and lenalidomide, have significantly improved response rates and are the standard
      of care for induction regimens. Although the timing and role of autologous stem
      cell transplant are now being questioned, it remains an important part of the
      treatment paradigm in eligible patients. In addition, the concept of extended
      sequential therapy has recently emerged, including consolidation and/or
      maintenance in both the post-transplant setting and in nontransplant candidates.
      In this article we focus on management strategies in newly diagnosed multiple
      myeloma, including choice of induction regimens in transplant-eligible and 
      ineligible patients, as well as the role of autologous stem cell transplant,
      consolidation therapy and maintenance therapy.

PMID- 24286006
TI  - Secondary amyloidosis in a patient carrying mutations in the familial
      Mediterranean fever (FMF) and tumour necrosis factor receptor-1 syndrome (TRAPS)
      genes.
AB  - Secondary amyloidosis (AA) is characterized by the extracellular tissue
      deposition of fibrils composed of fragments of an acute-phase reactant protein,
      serum amyloid A (SAA), due to chronic inflammatory diseases, infections and
      several neoplasms. AA amyloidosis may also complicate several hereditary
      diseases, where genetic factors play a pivotal role in the expression of
      amyloidosis. Familial Mediterranean fever (FMF) and tumour necrosis factor
      receptor-1 syndrome (TRAPS) are the most frequently involved. We describe a case
      of a 21-year-old Romanian woman who presented at the 35th week of gestation with
      acute abdominal pain, nausea and vomiting. The laboratory workup performed after
      delivery showed proteinuria in the nephrotic range and increased SAA protein.
      Kidney amyloid deposits were detected and genetic testing for secondary
      amyloidosis was performed identifying two mutations, one involving the gene of
      FMF (MEFV), and the other involving the tumour necrosis factor receptor-1 gene
      (TNFRSF1A). To our knowledge, this is the first case in the literature where
      secondary amyloidosis develops in a patient carrying mutations involving the
      genes of both FMF and TRAPS.

PMID- 24286007
TI  - The variable course of women with X-linked Alport Syndrome.
AB  - X-linked Alport syndrome (XLAS) arises from mutations in the COL4A5 gene encoding
      the alpha5-chain of type IV collagen and is associated with hematuria, ocular
      abnormalities and high-tone sensorineural hearing loss. Nearly all affected males
      have decreased kidney function resulting in end-stage renal disease (ESRD) as
      early as the second decade of life. It was long thought that affected females had
      a benign outcome; however, in recent decades, it has become quite clear that they
      too are at risk for developing nephrotic syndrome, decreased kidney function and
      ESRD. We report two young females presenting with microscopic hematuria and
      proteinuria diagnosed with XLAS on renal biopsy. Both developed nephrotic-range
      proteinuria and progressive renal insufficiency. Additionally, both developed
      extra-renal manifestations of XLAS. The ultrastructural and immunofluorescence
      features on kidney biopsy were instrumental in making the diagnosis of
      heterozygous XLAS as neither patient had a family history of AS.

PMID- 24286008
TI  - Mitochondrial bioenergetics is defective in presymptomatic Tg2576 AD mice.
AB  - Alzheimer's disease (AD) is an age-related dementia, with the pathological
      hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss
      of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as
      a contributing factor to the cognitive decline observed in AD. We hypothesized
      that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial
      respiration is impaired early in synaptic terminals, which are vital to cognitive
      performance, preferentially in cognitive centers of the brain. We compared oxygen
      consumption in synaptosomal and perikaryal mitochondria prepared from the
      cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice.
      Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in
      the cerebral cortex specifically in synaptosomal fraction, while the perikaryal
      mitochondria were unaffected. Neither mitochondrial fraction was affected in the
      cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic
      defect in synaptic terminals of mice overexpressing mutant beta-amyloid, in
      particular in an area of the brain important to cognition, points to an early
      role of mitochondrial defects in the onset of cognitive deficits in AD.

PMID- 24286010
TI  - Homeless aging veterans in transition: a life-span perspective.
AB  - The need for counseling and career/educational services for homeless veterans has
      captured political and economic venues for more than 25 years. Veterans are three
      times more likely to become homeless than the general population if veterans live
      in poverty or are minority veterans. This mixed methods study emphasized a life
      span perspective approach for exploring factors influencing normative aging and
      life-quality of 39 homeless veterans in Alabama and Florida. Seven descriptive
      quantitative and qualitative research questions framed the investigation. Study
      participants completed a quantitative survey reflecting their preferences and
      needs with a subset of the sample (N = 12) also participating in individual
      qualitative interview sessions. Thirty-two service providers and stakeholders
      completed quantitative surveys. Empirical and qualitative data with appropriate
      triangulation procedures provided interpretive information relative to a life
      span development perspective. Study findings provide evidence of the need for
      future research efforts to address strategies that focus on the health and
      economic challenges of veterans before they are threatened with the possibility
      of homelessness. Implications of the study findings provide important information
      associated with the premise that human development occurs throughout life with
      specific characteristics influencing the individual's passage. Implications for
      aging/homelessness research are grounded in late-life transitioning and human
      development intervention considerations. 

PMID- 24286009
TI  - The impact of sleeve gastrectomy on hyperlipidemia: a systematic review.
AB  - BACKGROUND: Weight loss and reduction in comorbidities can be achieved by
      longitudinal sleeve gastrectomy (LSG). Existing evidence suggests that LSG
      resolves or improves hyperlipidemia in morbidly obese patients. The aim of this
      study was to systematically review the effect of LSG on hyperlipidemia. METHODS:
      A systematic literature search was conducted from English-language studies
      published from 2000 to 2012 for the following databases: MEDLINE, EMBASE, CINAHL,
      PubMed, Clinical evidence, Scopus, Dara, Web of Sciences, TRIP, Health Technology
      Database, Cochrane library, and PsycINFO. RESULTS: A total of 4,211 articles were
      identified in the initial search, and 4,185 articles were excluded based on the
      exclusion criteria. Twenty-six studies met the inclusion criteria for this
      systematic review, involving 3,591 patients. The mean preoperative body mass
      index (BMI) was 48 +/- 7.0 kg/m(2) (range 37.2-65.3). The mean postoperative BMI
      was 35 +/- 5.9 kg/m(2) (range 26.3-49). The mean percentage of excess weight loss
      (EWL) was 63.1% (range 37.7-84.5), with a mean followup of 19.1 months (range 6
      60). The mean levels of pre and post operative cholesterol were 194.4 +/- 12.3
      mg/dL (range 178-213) and 181 +/- 16.3 mg/dL (range 158-200), respectively.
      CONCLUSION: Most patients with hyperlipidemia showed improvement or resolution of
      lipid profiles after LSG. Based on this systematic review, LSG has a significant
      effect on hyperlipidemia in the form of resolution or improvement in the majority
      of patients.

PMID- 24286011
TI  - Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine
      Model of Cutaneous Squamous Cell Carcinoma.
AB  - Epidemiological studies support a link between cumulative sun exposure and
      cutaneous squamous cell carcinoma (SCC) development. However, the presumed
      effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the
      sexes have not been formally investigated. We examined differences in ultimate
      tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks.
      Additionally, we investigated the effect of continued UVB exposure on the
      efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant
      (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated
      mice in the 25-week UVB exposure model exhibited an increased tumor burden and a
      higher percentage of malignant tumors compared to mice in the 10-week exposure
      model, which correlated with increases in total and mutant p53-positive epidermal
      cells. Only topical diclofenac decreased tumor number and burden in both sexes
      regardless of UVB exposure length. These data support the commonly assumed but
      not previously demonstrated fact that increased cumulative UVB exposure increases
      the risk of UVB-induced SCC development and can also affect therapeutic
      efficacies. Our study suggests that cessation of UVB exposure by at-risk patients
      may decrease tumor development and that topical NSAIDs such as diclofenac may be
      chemopreventive. 

PMID- 24286012
TI  - Light Reduction Capabilities of Homemade and Commercial Incubator Covers in NICU.
AB  - Reduction of high-risk neonates' exposure to aversive light stimulation is an
      important component of developmentally supportive care. In neonatal intensive
      care unit (NICU), usually light is reduced by reducing the room's light level or
      by using incubator covers. Many types of incubator covers are in use, including
      homemade and commercial covers. A comparative study was used to determine the
      light reducing capabilities of 19 homemade incubator covers, 2 commercial covers,
      and 1 receiving blanket. The covers were tested by covering and uncovering an
      incubator and an oxygen hood in the NICU during daytime and nighttime lightings.
      The light reducing capabilities value was determined for each cover using an
      Extech light dosimeter when the cover was placed over and removed from an
      oxyhood, and an incubator. The study showed that the light reducing capability of
      the commercial covers was 91.2%, the homemade covers capability was 72.1%, and
      the receiving blankets capability was 55.1%. A significant difference between the
      commercial and homemade covers was found (F = 452.50, P < 0.00). Commercial
      incubator covers are the most effective covers to achieve light reduction;
      homemade covers can be effective if made large enough so that they completely
      cover all sides of the incubator. 

PMID- 24286013
TI  - Neurofibromatosis type 1 and diabetes mellitus: an unusual association.
AB  - Neurofibromatosis type 1 is a multisystemic disease. It may manifest as
      abnormalities of the nervous tissue, bones, soft tissue, or skin. Autoimmune
      disease associated with NF1 can be seen. Diabetes mellitus is rarely seen in
      association with NF1. Here, we report a case with established NF1 who also had a
      diagnosis of diabetes mellitus. 

PMID- 24286014
TI  - A rare case of a pure testicular seminoma presenting 7 years after a pineal
      germinoma.
AB  - Pure testicular seminomas occurring in patients with previous intracranial germ
      cell tumours are extremely rare. We present such a case. A 37-year-old gentleman
      presented to urology after previously being treated for a pineal germinoma with
      steroids and radiotherapy. On routine followup, he described symptoms of a
      testicular seminoma. This was managed surgically with radical orchidectomy. We
      discuss the possible causes of such an association with a review of the
      literature. 

PMID- 24286016
TI  - Comparative Analysis of the Volatile Components of Agrimonia eupatoria from
      Leaves and Roots by Gas Chromatography-Mass Spectrometry and Multivariate Curve
      Resolution.
AB  - Gas chromatography-mass spectrometry and multivariate curve resolution were
      applied to the differential analysis of the volatile components in Agrimonia
      eupatoria specimens from different plant parts. After extracted with water
      distillation method, the volatile components in Agrimonia eupatoria from leaves
      and roots were detected by GC-MS. Then the qualitative and quantitative analysis
      of the volatile components in the main root of Agrimonia eupatoria was completed
      with the help of subwindow factor analysis resolving two-dimensional original
      data into mass spectra and chromatograms. 68 of 87 separated constituents in the
      total ion chromatogram of the volatile components were identified and quantified,
      accounting for about 87.03% of the total content. Then, the common peaks in leaf
      were extracted with orthogonal projection resolution method. Among the components
      determined, there were 52 components coexisting in the studied samples although
      the relative content of each component showed difference to some extent. The
      results showed a fair consistency in their GC-MS fingerprint. It was the first
      time to apply orthogonal projection method to compare different plant parts of
      Agrimonia eupatoria, and it reduced the burden of qualitative analysis as well as
      the subjectivity. The obtained results proved the combined approach powerful for
      the analysis of complex Agrimonia eupatoria samples. The developed method can be
      used to further study and quality control of Agrimonia eupatoria. 

PMID- 24286017
TI  - Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two
      Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum.
AB  - A reverse phase stability indicating HPLC method for simultaneous determination
      of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable)
      and in serum has been developed and validated. Mobile phase ingredients consist
      of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow
      rate 1.0 mL/min using a Hibar MU Bondapak ODS C18 column monitored at dual
      wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol,
      respectively. The drugs were subjected to stress conditions of hydrolysis
      (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule
      drastically while there was not so much significant effect of other stress
      conditions. The calibration curve was linear with a correlation coefficient of
      0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the
      range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and
      limit of quantification for both phloroglucinol and trimethylphloroglucinol. The
      method was validated in accordance with ICH guidelines and was applied
      successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol
      in bulk, injectable form and physiological fluid. Forced degradation studies
      proved the stability indicating abilities of the method. 

PMID- 24286015
TI  - HIV and Bone Disease: A Perspective of the Role of microRNAs in Bone Biology upon
      HIV Infection.
AB  - Increased life expectancy and the need for long-term antiretroviral therapy have
      brought new challenges to the clinical management of HIV-infected individuals.
      The prevalence of osteoporosis and fractures is increased in HIV-infected
      patients; thus optimal strategies for risk management and treatment in this group
      of patients need to be defined. Prevention of bone loss is an important component
      of HIV care as the HIV population grows older. Understanding the mechanisms by
      which HIV infection affects bone biology leading to osteoporosis is crucial to
      delineate potential adjuvant treatments. This review focuses on HIV-induced
      osteoporosis within the context of microRNAs (miRNAs) by reviewing first basic
      concepts of bone biology as well as current knowledge of the role of miRNAs in
      bone development. Evidence that HIV-associated osteoporosis is in part
      independent of therapies employed to treat HIV (HAART) is supported by cross
      sectional and longitudinal studies and is the focus of this review. 

PMID- 24286018
TI  - Unique Pattern of Overexpression of Raf-1 Kinase Inhibitory Protein in Its
      Inactivated Phosphorylated Form in Human Multiple Myeloma.
AB  - Multiple myeloma (MM) is the second most common hematological and incurable
      malignancy of plasma cells with low proliferative activity in the bone marrow. MM
      patients initially respond to conventional therapy, however, many develop
      resistance and recurrences occur. We have identified RKIP as a novel gene product
      that is differentially overexpressed in MM cell lines and MM tissues compared to
      other studied tumors and normal bone marrow. This overexpression consisted, in
      large part, of a phosphorylated inactive form of RKIP at Ser153 (p-Ser153 RKIP).
      In contrast to RKIP, p-Ser153 RKIP lacks its ability to inhibit the MAPK
      signaling pathway. The overexpression of p-Ser153 RKIP in MM cell lines and MM
      tissues was further validated in a mouse model carrying a human MM xenograft,
      namely, LAGlambda-1B. Bioinformatic analyses from databases support the presence
      of increased RKIP mRNA expression in MM compared to normal plasma cells. In these
      databases, high RKIP levels in MM are also correlated with the nonhyperdiploid
      status and the presence of IgH translocations, parameters that generally display
      more aggressive clinical features and shorter patients' survival irrespective of
      the treatment. Since RKIP expression regulates both the NF-kappaB and MAPK
      survival pathways, the overexpression of "inactive" p-Ser153 RKIP in MM might
      contribute positively to the overall cell survival/antiapoptotic phenotype and
      drug resistance of MM through the constitutive activation of survival pathways
      and downstream the transcription of anti-apoptotic gene products. The
      overexpression of RKIP and p-Ser153 RKIP in MM is the first demonstration in the
      literature, since in most tumor tissues the expression of RKIP is very low and
      the expression of p-Ser153 RKIP is much lower. The relationship between the
      levels of active RKIP and inactive p-Ser153 RKIP in MM may be of prognostic
      significance, and the regulation of RKIP activity may be a target for therapeutic
      intervention.

PMID- 24286019
TI  - Dynamics of Elective Case Cancellation for Inpatient and Outpatient in an
      Academic Center.
AB  - BACKGROUND: Unexpected surgical cancellation is common and can have significant
      adverse effects. Cancellation rates vary because of a lack of a standard
      definition, different patient populations and study methodology. We hypothesized
      that case cancellation has a different pattern in a dedicated ambulatory surgical
      center compared to a general operating room (OR) setting in a large academic
      center without an anesthesia preoperative evaluation center necessitating
      evaluation by the various surgeons. METHODS: Elective cases in general OR and in
      the ambulatory surgical center were included in this study. Elective cases are
      defined as the non-emergent cases scheduled before 8:00 am on the day of surgery.
      A cancelled case was defined as a scheduled procedure which is not performed on
      the scheduled procedure day. Case cancellation was monitored in real time using
      an electronic patient flow system (Navicare). As soon as the case is cancelled,
      the reason for the cancellation was obtained from the surgeon, the
      anesthesiologist, the OR coordinated nurses and/or the floor nurse. In the day
      surgical center, the cancelled cases were followed to determine whether/when they
      were rescheduled. RESULTS: 4261 elective cases were included in this
      investigation, including 2751 cases in the general OR and 1510 cases in the
      ambulatory surgical center. A total of 283 cases (6.6%) were cancelled which
      include 206 cases from the general OR and 77 from the ambulatory surgical center.
      The cancellation rate in the general OR was 7.5%, among which inpatients have the
      highest cancellation rate of 18.1%, followed by outpatients at 4.6%, and same day
      admission at the lowest cancellation rate of 2.0%. The top 3 reasons for
      cancellation in general OR werein adequate preoperative preparation 29.4 +/-
      4.5%, medical condition change 28.5 +/- 10.2%; and scheduling issue 20.2 +/-
      7.1%. Most (59.2 +/- 8.9%) of the cancellations was considered preventable, 12.3
      +/- 5.9% was considered potentially preventable, and 28.5 +/- 10.2% were not
      preventable (such as patient condition changes). The cancellation rate in the
      ambulatory surgical center was 5.1%. The major reason for cancellation was
      patient no show 75.8 +/- 5.2 %, 61% of those no show patients were rescheduled
      and the mean delay in surgery was 18 days (range from 1 day to 84 days).
      CONCLUSIONS: Case cancellation is not un-common in a large academic center
      without a preoperative evaluation clinic. The dynamics of case cancellation are
      different in an ambulatory surgical center as compared to the general OR.
      Inpatients have the highest cancellation rate associated with inadequate
      preoperative preparation and scheduling, this should be preventable via adopting
      proper systems of evaluation and preparation. Most of the case cancellations in
      the ambulatory surgical center are from patient no show, suggesting that
      administrative strategies to reduce this issue should be implemented. The
      patients admitted on the same day of surgery had the lowest cancellation rate
      requiring minimal intervention.

PMID- 24286021
TI  - Smoke-Free Policies in the Workplace and in the Home among American Indians.
AB  - OBJECTIVES: American Indians are more likely to smoke, less likely to have smoke
      free homes, and potentially less likely to have worksite smoke-free policies. We
      examined correlates of smoke-free policies at home and work among a community
      based sample of American Indians in the Midwest. METHODS: We examined correlates
      of smoke-free policies at home and work in a sample of American Indians in the
      Midwest using a community-based participatory research approach. RESULTS: 66.7%
      were nonsmokers, 15.6% smoked on some days, and 17.6% smoked every day. The
      majority (72.4%) had complete smoke-free home policies, 13.1% had partial
      restrictions, and 14.5% had no rules. Moreover, 62.7% had complete smoke-free
      worksite policies, 27.9% had partial policies, and 9.4% had no worksite smoke
      free policies. Factors associated with having a complete smoke-free home policy
      included being a college graduate (p=.005) and a nonsmoker versus a nondaily
      (p=.006) or a daily smoker (p<.001). Correlates of having a complete smoke-free
      worksite policy included being female (p=.005) and a nonsmoker versus a nondaily
      (p=.03) or a daily smoker (p<.001). Having complete worksite policies was
      associated with having smoke-free homes (p<.001). CONCLUSIONS: Having complete
      worksite policies was related to having smoke-free home policies; both were
      associated with being a nonsmoker.

PMID- 24286022
TI  - An Ubiquitin-like Motif in ASK1 Mediates its Association with and Inhibition of
      the Proteasome.
AB  - Linear polyubiquitin is processed at LRLRGG sequences by deubiquitinating enzymes
      to make free monomeric ubiquitin. This LRLRGG ubiquitin-like motif is found in a
      limited number of mammalian non-ubiquitin proteins, including the MAP3K Apoptosis
      Signal-Regulating Kinase-1 (ASK1), which activates MAPK signaling pathways. The c
      terminus of ASK1 binds to the 19S cap of the proteasome allowing ASK1 to
      phosphorylate and inhibit proteasomal activity. We investigated whether the
      ubiquitin-like sequence in the c-terminus of ASK1 mediates its association with
      and inhibition of the proteasome. To test this we generated ASK1 with
      substitutions or deletions in this ubiquitin-like domain and examined the
      activation of cellular signaling and the association of ASK1 with the 19S cap of
      the proteasome. We show that ASK1 mutants have reduced association with the 19S
      cap of the proteasome, reduced capacity to inhibit the proteasome, and diminished
      ability to inhibit TNF-induced NF-kappaB activation. Mutant forms of ASK1 also
      had reduced capacity to activate JNK signaling, suggesting that the ubiquitin
      like motif in ASK1 is also important for coordinating the balance between JNK and
      NF-kappaB signaling. Together these results demonstrate that the ubiquitin-like
      sequence of ASK1 is important for binding to and inhibition of the proteasome,
      and for the coordinated activation of cellular NF-kappaB and JNK signaling.

PMID- 24286023
TI  - Reducing stigma toward seeking mental health treatment among adolescents.
AB  - PURPOSE: This study examined the effectiveness of an intervention to reduce
      explicit and implicit stigma-relevant attitudes toward mental illness and
      treatment-seeking and behavioural indicators of willingness to seek treatment.
      METHODS: Adolescents were randomly assigned to the experimental (education about
      mental illness and treatment involving psychoeducation and contact (via DVD) with
      an affected individual) or control intervention (education about tobacco).
      RESULTS: Findings suggest the stigma intervention was effective at reducing
      explicit but not implicit stigma-relevant attitudes. As hypothesized,
      participants receiving the experimental intervention reported less explicit
      stigma toward treatment and greater openness to personally seek treatment if they
      had also reported prior mental health treatment. CONCLUSIONS AND IMPLICATIONS:
      These findings support the potential for a brief educational intervention among
      adolescents to reduce negative attitudes toward mental health treatment, but
      raise questions about how to effectively address implicit stigma as well as the
      importance of translating stigma reduction into behavior changes.

PMID- 24286024
TI  - Reduced FDG-PET brain metabolism and executive function predict clinical
      progression in elderly healthy subjects.
AB  - Brain changes reminiscent of Alzheimer disease (AD) have been previously reported
      in a substantial portion of elderly cognitive healthy (HC) subjects. The major
      aim was to evaluate the accuracy of MRI assessed regional gray matter (GM)
      volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and
      neuropsychological test scores to identify those HC subjects who subsequently
      convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54
      healthy control (HC) subjects a priori defined region of interest (ROI) values of
      medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic
      regression analyses, these ROI values were tested together with
      neuropsychological test scores (free recall, trail making test B (TMT-B)) as
      predictors of HC conversion during a clinical follow-up between 3 and 4 years. In
      voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters
      and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or
      AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of
      conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95%
      CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p =
      0.07). TMT-B but not the free recall tests were a significant predictor (AUC =
      71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC
      was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison
      showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal
      cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and
      executive function show a clinically acceptable accuracy for predicting clinical
      progression in elderly HC subjects. 

PMID- 24286026
TI  - BCL-XL mediates the strong selective advantage of a 20q11.21 amplification
      commonly found in human embryonic stem cell cultures.
AB  - Human embryonic stem cells (hESCs) regularly acquire nonrandom genomic
      aberrations during culture, raising concerns about their safe therapeutic
      application. The International Stem Cell Initiative identified a copy number
      variant (CNV) amplification of chromosome 20q11.21 in 25% of hESC lines
      displaying a normal karyotype. By comparing four cell lines paired for the
      presence or absence of this CNV, we show that those containing this amplicon have
      higher population doubling rates, attributable to enhanced cell survival through
      resistance to apoptosis. Of the three genes encoded within the minimal amplicon
      and expressed in hESCs, only overexpression of BCL2L1 (BCL-XL isoform) provides
      control cells with growth characteristics similar to those of CNV-containing
      cells, whereas inhibition of BCL-XL suppresses the growth advantage of CNV cells,
      establishing BCL2L1 as a driver mutation. Amplification of the 20q11.21 region is
      also detectable in human embryonal carcinoma cell lines and some
      teratocarcinomas, linking this mutation with malignant transformation. 

PMID- 24286025
TI  - Multiple structural maintenance of chromosome complexes at transcriptional
      regulatory elements.
AB  - Transcription factors control cell-specific gene expression programs by binding
      regulatory elements and recruiting cofactors and the transcription apparatus to
      the initiation sites of active genes. One of these cofactors is cohesin, a
      structural maintenance of chromosomes (SMC) complex that is necessary for proper
      gene expression. We report that a second SMC complex, condensin II, is also
      present at transcriptional regulatory elements of active genes during interphase
      and is necessary for normal gene activity. Both cohesin and condensin II are
      associated with genes in euchromatin and not heterochromatin. The two SMC
      complexes and the SMC loading factor NIPBL are particularly enriched at super
      enhancers, and the genes associated with these regulatory elements are especially
      sensitive to reduced levels of these complexes. Thus, in addition to their well
      established functions in chromosome maintenance during mitosis, both cohesin and
      condensin II make important contributions to the functions of the key
      transcriptional regulatory elements during interphase. 

PMID- 24286020
TI  - Trial watch: Dendritic cell-based interventions for cancer therapy.
AB  - Dendritic cells (DCs) occupy a privileged position at the interface between
      innate and adaptive immunity, orchestrating a large panel of responses to both
      physiological and pathological cues. In particular, whereas the presentation of
      antigens by immature DCs generally results in the development of immunological
      tolerance, mature DCs are capable of priming robust, and hence therapeutically
      relevant, adaptive immune responses. In line with this notion, functional defects
      in the DC compartment have been shown to etiologically contribute to pathological
      conditions including (but perhaps not limited to) infectious diseases, allergic
      and autoimmune disorders, graft rejection and cancer. Thus, the possibility of
      harnessing the elevated immunological potential of DCs for anticancer therapy has
      attracted considerable interest from both researchers and clinicians over the
      last decade. Alongside, several methods have been developed not only to isolate
      DCs from cancer patients, expand them, load them with tumor-associated antigens
      and hence generate highly immunogenic clinical grade infusion products, but also
      to directly target DCs in vivo. This intense experimental effort has culminated
      in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T,
      Provenge(r)) for the treatment of asymptomatic or minimally symptomatic
      metastatic castration-refractory prostate cancer. As an update to the latest
      Trial Watch dealing with this exciting field of research (October 2012), here we
      summarize recent advances in DC-based anticancer regimens, covering both high
      impact studies that have been published during the last 13 mo and clinical trials
      that have been launched in the same period to assess the antineoplastic potential
      of this variant of cellular immunotherapy.

PMID- 24286027
TI  - Functional differences in engineered myocardium from embryonic stem cell-derived
      versus neonatal cardiomyocytes.
AB  - Stem cell-derived cardiomyocytes represent unique tools for cell- and tissue
      based regenerative therapies, drug discovery and safety, and studies of
      fundamental heart-failure mechanisms. However, the degree to which stem cell
      derived cardiomyocytes compare to mature cardiomyocytes is often debated. We
      reasoned that physiological metrics of engineered cardiac tissues offer a means
      of comparison. We built laminar myocardium engineered from cardiomyocytes that
      were differentiated from mouse embryonic stem cell-derived cardiac progenitors or
      harvested directly from neonatal mouse ventricles, and compared their anatomy and
      physiology in vitro. Tissues assembled from progenitor-derived myocytes and
      neonate myocytes demonstrated similar cytoskeletal architectures but different
      gap junction organization and electromechanical properties. Progenitor-derived
      myocardium had significantly less contractile stress and slower longitudinal
      conduction velocity than neonate-derived myocardium, indicating that the
      developmental state of the cardiomyocytes affects the electromechanical function
      of the resultant engineered tissue. These data suggest a need to establish
      performance metrics for future stem cell applications. 

PMID- 24286028
TI  - Sca1-derived cells are a source of myocardial renewal in the murine adult heart.
AB  - Although the mammalian heart is one of the least regenerative organs in the body,
      recent evidence indicates that the myocardium undergoes a certain degree of
      renewal to maintain homeostasis during normal aging. However, the cellular origin
      of cardiomyocyte renewal has remained elusive due to lack of lineage tracing
      experiments focusing on putative adult cardiac precursor cells. We have generated
      triple-transgenic mice based on the tet-cre system to identify descendants of
      cells that have expressed the stem cell marker Sca1. We found a significant and
      lasting contribution of Sca1-derived cells to cardiomyocytes during normal aging.
      Ischemic damage and pressure overload resulted in increased differentiation of
      Sca1-derived cells to the different cell types present in the heart. Our results
      reveal a source of cells for cardiomyocyte renewal and provide a possible
      explanation for the limited contribution of Sca1-derived cells to myocardial
      repair under pathological conditions. 

PMID- 24286029
TI  - The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26
      expression to promote germline stem cell self-renewal.
AB  - Translational regulation plays an essential role in Drosophila ovarian germline
      stem cell (GSC) biology. GSC self-renewal requires two translational repressors,
      Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation
      factors in the stem cells. The molecular mechanisms underlying this translational
      repression remain unknown. Here, we show that the CCR4 deadenylase is required
      for GSC self-renewal and that Nos and Pum act through its recruitment onto
      specific mRNAs. We identify mei-P26 mRNA as a direct and major target of
      Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of
      the Trim-NHL tumor suppressor family that has conserved functions in stem cell
      lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in
      GSC self-renewal. These results identify the molecular mechanism of Nos/Pum
      function in GSC self-renewal and reveal the role of CCR4-NOT-mediated
      deadenylation in regulating the balance between GSC self-renewal and
      differentiation. 

PMID- 24286030
TI  - A Cdx4-Sall4 regulatory module controls the transition from mesoderm formation to
      embryonic hematopoiesis.
AB  - Deletion of caudal/cdx genes alters hox gene expression and causes defects in
      posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only
      partially explain these phenotypes. To gain deeper insight into Cdx4 function, we
      performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with gene
      expression profiling in zebrafish, and identified the transcription factor spalt
      like 4 (sall4) as a Cdx4 target. ChIP-seq revealed that Sall4 bound to its own
      gene locus and the cdx4 locus. Expression profiling showed that Cdx4 and Sall4
      coregulate genes that initiate hematopoiesis, such as hox, scl, and lmo2.
      Combined cdx4/sall4 gene knockdown impaired erythropoiesis, and overexpression of
      the Cdx4 and Sall4 target genes scl and lmo2 together rescued the erythroid
      program. These findings suggest that auto- and cross-regulation of Cdx4 and Sall4
      establish a stable molecular circuit in the mesoderm that facilitates the
      activation of the blood-specific program as development proceeds. 

PMID- 24286031
TI  - High yields of oligodendrocyte lineage cells from human embryonic stem cells at
      physiological oxygen tensions for evaluation of translational biology.
AB  - We have established and efficient system to specify NG2/PDGF-Ralpha/OLIG2+
      oligodendrocyte precursor cells (OPCs) from human embryonic stem cells (hESCs) at
      low, physiological (3%) oxygen levels. This was achieved via both forebrain and
      spinal cord origins, with up to 98% of cells expressing NG2. Developmental
      insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2
      induction via ventral forebrain pathways. The OPCs mature in vitro to express O4
      (46%) and subsequently become galactocerebroside (GALC), O1, and myelin basic
      protein-positive (MBP+) multibranching oligodendrocytes. These were cultured
      alongside hESC-derived neurons. The electrophysiological properties of human OPCs
      are similar to those of rat OPCs, with large voltage-gated sodium currents and
      the ability to fire action potentials. Exposure to a selective retinoid X
      receptor agonist increased the proportion of O4+ oligodendrocytes that express
      MBP from 5% to 30%. Thus, we have established a developmentally engineered system
      to investigate the biological properties of human OPCs and test the effects of
      putative remyelinating agents prior to clinical application. 

PMID- 24286032
TI  - Induced pluripotent stem cell modeling of multisystemic, hereditary transthyretin
      amyloidosis.
AB  - Familial transthyretin amyloidosis (ATTR) is an autosomal-dominant protein
      folding disorder caused by over 100 distinct mutations in the transthyretin (TTR)
      gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in
      target organs, chiefly the heart and peripheral nervous system, highlighting the
      need for a model capable of recapitulating the multisystem complexity of this
      clinically variable disease. Here, we describe the directed differentiation of
      ATTR patient-specific iPSCs into hepatocytes that produce mutant TTR, and the
      cardiomyocytes and neurons normally targeted in the disease. We demonstrate that
      iPSC-derived neuronal and cardiac cells display oxidative stress and an increased
      level of cell death when exposed to mutant TTR produced by the patient-matched
      iPSC-derived hepatocytes, recapitulating essential aspects of the disease in
      vitro. Furthermore, small molecule stabilizers of TTR show efficacy in this
      model, validating this iPSC-based, patient-specific in vitro system as a platform
      for testing therapeutic strategies. 

PMID- 24286033
TI  - Analysis of SOX2-expressing cell populations derived from human pluripotent stem
      cells.
AB  - SOX2 is involved in several cell and developmental processes, including
      maintenance of embryonic stem cells, differentiation of neural progenitor cells,
      and patterning of gut endoderm. To study its role in a human system, we generated
      a human embryonic stem cell (hESC) line harboring a reporter gene encoding GFP in
      the SOX2 locus. This SOX2 reporter line faithfully recapitulates expression of
      the SOX2 gene in undifferentiated human pluripotent stem cells (hPSCs), neural
      progenitor cells (NPCs), and anterior foregut endoderm (AFE). In undifferentiated
      hESCs, GFP expression corresponds to those cells with highest levels of
      expression of genes associated with the pluripotent state. In NPCs, expression of
      GFP can be employed to isolate cells expressing markers associated with NPC
      multipotency. In AFE, we used transcriptome-wide expression analysis to identify
      cell surface markers with elevated expression in this population, thereby
      facilitating isolation and purification of this hPSC-derived cell population. 

PMID- 24286035
TI  - Impact of PRRSV on activation and viability of antigen presenting cells.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is one of the most important
      diseases of swine industry. The causal agent, PRRS-virus (PRRSV), is able to
      evade the host immune response and survive in the organism causing transient
      infections. Despite all scientific efforts, there are still some gaps in the
      knowledge of the pathogenesis of this disease. Antigen presenting cells (APCs),
      as initiators of the immune response, are located in the first line of defense
      against microorganisms, and are responsible for antigen recognition, processing
      and presentation. Dendritic cells (DCs) are the main type of APC involved in
      antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV
      replication in DCs may trigger off different mechanisms to impair the onset of a
      host effective immune response against the virus. On the one side, PRRSV may
      impair the basic functions of DCs by regulating the expression of major
      histocompatibility complex class II and CD80/86. Other strategy followed by the
      virus is the induction of cell death of APCs by apoptosis, necrosis or both of
      them. The impairment and/or cell death of APCs could lead to a failure in the
      onset of an efficient immune response, as long as cells could not properly
      activate T cells. Future aspects to take into account are also discussed in this
      review. 

PMID- 24286036
TI  - Genetic analysis of structural proteins in the adsorption apparatus of
      bacteriophage epsilon 15.
AB  - AIM: To probe the organizational structure of the adsorption apparatus of
      bacteriophage epsilon 15 (E15) using genetic and biochemical methodology METHODS:
      Hydroxylamine was used to create nonsense mutants of bacteriophage E15. The
      mutants were then screened for defects in their adsorption apparatus proteins,
      initially by measuring the concentrations of free tail spike proteins in lysates
      of cells that had been infected by the phage mutants under non-permissive growth
      conditions. Phage strains whose infected cell lysates contained above-average
      levels of free tail spike protein under non-permissive growth conditions were
      assumed to contain nonsense mutations in genes coding for adsorption apparatus
      proteins. These mutants were characterized by classical genetic mapping methods
      as well as automated sequencing of several of their genes. Finally, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography were used
      to examine the protein compositions of the radioactive particles produced when
      the various mutants were grown on a non-permissive host cell in the presence of
      (35)S-methionine and co-purified along with E15wt phage on CsCl block gradients.
      RESULTS: Our results are consistent with gp4 forming the portal ring structure of
      E15. In addition, they show that proteins gp15 and gp17 likely comprise the
      central tube portion of the E15 adsorption apparatus, with gp17 being more
      distally positioned than gp15 and dependent upon both gp15 and gp16 for its
      attachment. Finally, our data indicates that tail spike proteins comprised of
      gp20 can assemble onto nascent virions that contain gp7, gp10, gp4 and packaged
      DNA, but which lack both gp15 and gp17, thereby forming particles that are of
      sufficient stability to survive CsCl buoyant density centrifugation. CONCLUSION:
      The portal ring (gp4) of E15 is bound to tail spikes (gp20) and the tail tube
      (gp15 and gp17); gp17's attachment requires both gp15 and gp16.

PMID- 24286034
TI  - Emerging Role of Sphingosine-1-phosphate in Inflammation, Cancer, and
      Lymphangiogenesis.
AB  - The main function of the lymphatic system is to control and maintain fluid
      homeostasis, lipid transport, and immune cell trafficking. In recent years, the
      pathological roles of lymphangiogenesis, the generation of new lymphatic vessels
      from preexisting ones, in inflammatory diseases and cancer progression are
      beginning to be elucidated. Sphingosine-1-phosphate (S1P), a bioactive lipid,
      mediates multiple cellular events, such as cell proliferation, differentiation,
      and trafficking, and is now known as an important mediator of inflammation and
      cancer. In this review, we will discuss recent findings showing the emerging role
      of S1P in lymphangiogenesis, in inflammation, and in cancer. 

PMID- 24286037
TI  - Appropriate roles for the subscriber, publisher, editor, author, and reviewer in
      the archives of plastic surgery.
AB  - Authors, editors and reviewers, publishers, and subscribers all play their role
      in scientific journals. These 5 stakeholders are essential to journals. In this
      paper, firstly, I briefly summarize the role of each journal stakeholder and
      their respective goals. Secondly, the status of each participant in the Archives
      of Plastic Surgery is described. Finally, I propose an appropriate role and plan
      for each of them. Specific roles and responsibilities include the following:
      subscribers should welcome and submit the critiques of published papers in
      letters to the editor. Publishers should trust editors and provide them with
      adequate financial support for ongoing quality improvement of the journal. The
      editor-in-chief should be given a sufficient period of time-several years-to
      build up journal quality and train the incoming editor. The editors, including
      section editors, are also responsible for increasing the author pool. One editor
      might be designated a 'devil's referee', that is, a kind of devil's advocate with
      the responsibility of examining the originality of the manuscript, taking a
      skeptical view of the manuscript, and looking for holes in the methods and
      results of reported experiments. Authors' responsibilities include submitting
      manuscripts with scientific integrity and being ready to take responsibility for
      their articles even long after publication. Finally, reviewers' responsibilities
      include identifying similar articles not cited. Reviewers are also welcome to
      write a discussion on the article they review. 

PMID- 24286039
TI  - Latent Transforming Growth Factor-beta1 Functionalised Electrospun Scaffolds
      Promote Human Cartilage Differentiation: Towards an Engineered Cartilage
      Construct.
AB  - BACKGROUND: To overcome the potential drawbacks of a short half-life and dose
      related adverse effects of using active transforming growth factor-beta 1 for
      cartilage engineering, a cell-mediated latent growth factor activation strategy
      was developed incorporating latent transforming growth factor-beta1 (LTGF) into
      an electrospun poly(L-lactide) scaffold. METHODS: The electrospun scaffold was
      surface modified with NH3 plasma and biofunctionalised with LTGF to produce both
      random and orientated biofunctionalised electrospun scaffolds. Scaffold surface
      chemical analysis and growth factor bioavailability assays were performed. In
      vitro biocompatibility and human nasal chondrocyte gene expression with these
      biofunctionalised electrospun scaffold templates were assessed. In vivo
      chondrogenic activity and chondrocyte gene expression were evaluated in athymic
      rats. RESULTS: Chemical analysis demonstrated that LTGF anchored to the scaffolds
      was available for enzymatic, chemical and cell activation. The biofunctionalised
      scaffolds were non-toxic. Gene expression suggested chondrocyte re
      differentiation after 14 days in culture. By 6 weeks, the implanted
      biofunctionalised scaffolds had induced highly passaged chondrocytes to re
      express Col2A1 and produce type II collagen. CONCLUSIONS: We have demonstrated a
      proof of concept for cell-mediated activation of anchored growth factors using a
      novel biofunctionalised scaffold in cartilage engineering. This presents a
      platform for development of protein delivery systems and for tissue engineering.

PMID- 24286038
TI  - Stem cells in plastic surgery: a review of current clinical and translational
      applications.
AB  - BACKGROUND: Stem cells are a unique cell population characterized by self-renewal
      and cellular differentiation capabilities. These characteristics, among other
      traits, make them an attractive option for regenerative treatments of tissues
      defects and for aesthetic procedures in plastic surgery. As research regarding
      the isolation, culture and behavior of stem cells has progressed, stem cells,
      particularly adult stem cells, have shown promising results in both translational
      and clinical applications. METHODS: The purpose of this review is to evaluate the
      applications of stem cells in the plastic surgery literature, with particular
      focus on the advances and limitations of current stem cell therapies. Different
      key areas amenable to stem cell therapy are addressed in the literature review;
      these include regeneration of soft tissue, bone, cartilage, and peripheral
      nerves, as well as wound healing and skin aging. RESULTS: The reviewed studies
      demonstrate promising results, with favorable outcomes and minimal complications
      in the cited cases. In particular, adipose tissue derived stem cell (ADSC)
      transplants appear to provide effective treatment options for bony and soft
      tissue defects, and non-healing wounds. ADSCs have also been shown to be useful
      in aesthetic surgery. CONCLUSIONS: Further studies involving both the basic and
      clinical science aspects of stem cell therapies are warranted. In particular, the
      mechanism of action of stem cells, their interactions with the surrounding
      microenvironment and their long-term fate require further elucidation. Larger
      randomized trials are also necessary to demonstrate the continued safety of
      transplanted stem cells as well as the efficacy of cellular therapies in
      comparison to the current standards of care.

PMID- 24286040
TI  - Effects of ischemic preconditioning of different intraoperative ischemic times of
      vascularized bone graft rabbit models.
AB  - BACKGROUND: Ischemic preconditioning has been shown to improve the outcomes of
      hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle
      tissues. However, to date, no report of ischemic preconditioning on vascularized
      bone grafts has been published. METHODS: Sixteen rabbits were divided into four
      groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each
      group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted
      of the tibia bone, from which the overlying muscle and skin were raised. The
      technique of ischemic preconditioning involved applying a vascular clamp to the
      pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain
      radiography and computed tomography imaging on the first, second, fourth, and
      sixth postoperative weeks. Following this, all of the rabbits were sacrificed and
      histological examinations were performed. RESULTS: The results showed that for
      clinical analysis of the skin flaps and bone grafts, the preconditioned groups
      showed better survivability. In the plain radiographs, except for two non
      preconditioned rabbits with intraoperative ischemic times of 6 hours, all began
      to show early callus formation at the fourth week. The computed tomography
      findings showed more callus formation in the preconditioned groups for all of the
      ischemic times except for the 18-hour group. The histological findings correlated
      with the radiological findings. There was no statistical significance in the
      difference between the two groups. CONCLUSIONS: In conclusion, ischemic
      preconditioning improved the survivability of skin flaps and increased callus
      formation during the healing process of vascularized bone grafts.

PMID- 24286041
TI  - The effects of topical agent (kelo-cote or contractubex) massage on the thickness
      of post-burn scar tissue formed in rats.
AB  - BACKGROUND: We conducted an experimental study to compare the effect of massage
      using topical agents (Kelo-cote or Contractubex) on scar formation by massaging
      the healed burn wound on the dorsal area of Sprague-Dawley (SD) rats. METHODS:
      Four areas of second degree contact burn were made on the dorsal area of each of
      15 SD rats, using a soldering iron 15 mm in diameter. After gross
      epithelialization in the defect, 15 SD rats were randomly divided into four
      groups: the Kelo-cote group, Contractubex group, Vaseline group, and control
      group. Rats in three of the groups (all but the Control group) were massaged
      twice per day for 5 minutes each day, while those in the Control group were left
      unattended. For histologic analysis, we performed a biopsy and evaluated the
      thickness of scar tissue. RESULTS: In the Kelo-cote and Contractubex groups, scar
      tissue thicknesses showed a significant decrease, compared with the Vaseline and
      control groups. However, no significant differences were observed between the
      Kelo-cote and Contractubex groups. In the Vaseline group, scar tissue thicknesses
      showed a significant decrease, compared with the control groups. CONCLUSIONS: The
      findings of this study suggest that massage using a topical agent is helpful in
      the prevention of scar formation and that massage only with lubricant (no use of
      a topical agent) also has a considerable effect, although not as much as the use
      of a topical agent. Thus, we recommend massage with a topical agent on the post
      burn scar as an effective method for decreasing the scar thickness.

PMID- 24286042
TI  - An analytical study of Mammalian bite wounds requiring inpatient management.
AB  - BACKGROUND: Mammalian bite injuries create a public health problem because of
      their frequency, potential severity, and increasing number. Some researchers have
      performed fragmentary analyses of bite wounds caused by certain mammalian
      species. However, little practical information is available concerning serious
      mammalian bite wounds that require hospitalization and intensive wound
      management. Therefore, the purpose of this study was to perform a general review
      of serious mammalian bite wounds. METHODS: We performed a retrospective review of
      the medical charts of 68 patients who were referred to our plastic surgery
      department for the treatment of bite wounds between January 2003 and October
      2012. The cases were analyzed according to the species, patient demographics,
      environmental factors, injury characteristics, and clinical course. RESULTS:
      Among the 68 cases of mammalian bite injury, 58 (85%) were caused by dogs, 8 by
      humans, and 2 by cats. Most of those bitten by a human and both of those bitten
      by cats were male. Only one-third of all the patients were children or
      adolescents. The most frequent site of injury was the face, with 40 cases,
      followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with
      secondary intention healing. Sixty-one patients underwent delayed procedures,
      including delayed direct closure, skin graft, composite graft, and local flap.
      CONCLUSIONS: Based on overall findings from our review of the 68 cases of
      mammalian bites, we suggest practical guidelines for the management of mammalian
      bite injuries, which could be useful in the treatment of serious mammalian bite
      wounds.

PMID- 24286043
TI  - A tie-over dressing using a silicone tube to graft deep wounds.
AB  - BACKGROUND: The most common cause of skin graft failure is the collection of
      blood or serous fluid underneath the graft. In our study, we describe the use of
      silicone tube for tie-over dressing to secure the skin graft margins with the aim
      of decreasing loss of the skin graft, particularly in grafting of deep wounds.
      METHODS: Between March 2008 and July 2011, we used this technique in 17 patients
      with skin defects with depths ranging from 3.5 to 8 mm (mean, 5.5 mm). First, the
      skin graft was sutured with 3/0 silk suture material from its corners. Then, a
      silicone round drain tube was sutured with 3/0 absorbable polyglactin 910 over
      the margins of the graft. Finally, long silk threads were tied over the bolus
      dressing, and the tie-over dressing was completed in the usual fashion. RESULTS:
      The mean follow-up was 7 months (range, 2-10 months) in the outpatient clinic.
      Graft loss on the graft margins due to hematoma or seroma was not developed. The
      results of adhesion between the graft and wound bed peripherally was excellent.
      CONCLUSIONS: In our study, we suggest that use of a silicone tube for additional
      pressure on the edges of skin grafts in case of reconstruction of deep skin
      defects.

PMID- 24286044
TI  - The functionality of facial appearance and its importance to a korean population.
AB  - BACKGROUND: Many people have an interest in the correction of facial scars or
      deformities caused by trauma. The increasing ability to correct such flaws has
      been one of the reasons for the increase in the popularity of facial plastic
      surgery. In addition to its roles in communication, breathing, eating, olfaction
      and vision, the appearance of the face also plays an important role in human
      interactions, including during social activities. However, studies on the
      importance of the functional role of facial appearance. As a function of the face
      are scare. Therefore, in the present study, we evaluated the importance of the
      functions of the face in Korea. METHODS: We conducted an online panel survey of
      300 participants (age range, 20-70 years). Each respondent was administered the
      demographic data form, Facial Function Assessment Scale, Rosenberg Self-Esteem
      Scale, and standard gamble questionnaires. RESULTS: In the evaluation on the
      importance of facial functions, a normal appearance was considered as important
      as communication, breathing, speech, and vision. Of the 300 participants, 85%
      stated that a normal appearance is important in social activities. CONCLUSIONS:
      The results of this survey involving a cross-section of the Korean population
      indicated that a normal appearance was considered one of the principal facial
      functions. A normal appearance was considered more important than the functions
      of olfaction and expression. Moreover, a normal appearance was determined to be
      an important facial function for leading a normal life in Korea.

PMID- 24286045
TI  - The merits of mannitol in the repair of orbital blowout fracture.
AB  - BACKGROUND: One of the main concerns in orbital blowout fracture repair is a
      narrow operation field, due mainly to the innate complex three dimensions of the
      orbit; however, a deep location and extensive area of the fracture and soft
      tissue edema can also cause concern. Swelling of the orbital contents progresses
      as the operation continues. Mannitol has been used empirically in glaucoma,
      cerebral hemorrhage, and orbital compartment syndrome for decompression. The
      authors adopted mannitol for the control of intraorbital edema and pressure in
      orbital blowout fracture repair. METHODS: This prospective study included 108
      consecutive patients who were treated for a pure blowout fracture from January
      2007 to October 2012. For group I, mannitol was administered during the
      operation. Under general anesthesia, all patients underwent surgery by open
      reduction and insertion of an absorbable mesh implant. The authors compared
      postoperative complications, the reoperation rate, operation time, and surgical
      field improvement between the two groups. RESULTS: In patients who received
      intraoperative administration of mannitol, the reoperation rate and operation
      time were decreased; however, the difference was not statistically significant.
      The total postoperative complication rates did not differ. Panel assessment for
      the intraoperative surgical field video recordings showed significantly improved
      vision in group I. CONCLUSIONS: For six years, mannitol proved itself an
      effective, reliable, and safe adjunctive drug in the repair of orbital blowout
      fractures. With its rapid onset and short duration of action, mannitol could be
      one of the best methods for obtaining a wider surgical field in blowout fracture
      defects.

PMID- 24286046
TI  - Two-Year Follow-up on the Use of Absorbable Mesh Plates in the Treatment of
      Medial Orbital Wall Fractures.
AB  - BACKGROUND: Absorbable materials offer many advantages in the reconstruction of
      orbital walls; however, the possibility of postoperative enophthalmos after
      complete absorption cannot be excluded. We evaluated the postoperative results of
      absorbable mesh plates used as onlay implanting on the medial orbital wall to
      determine whether they are suitable for medial orbital wall reconstruction.
      METHODS: The study included 20 patients with medial orbital wall fractures who
      were followed up for more than 2 years postoperatively. We used absorbable mesh
      plates in all of the patients. We measured the following: the changes in the
      expanded orbital volume by comparing the preoperative and postoperative computed
      tomography (CT) scans and the degree of clinical enophthalmos. RESULTS: There
      were no major complications associated with the use of absorbable materials such
      as infection, migration, or extrusion of mesh plates during the long-term follow
      up. The orbital volumetric changes between the preoperative and postoperative CT
      scans were not statistically significant. However, the expanded orbital volume
      was not related to the degree of clinical enophthalmos. CONCLUSIONS: The
      reconstructed orbital wall may provide supportive scar tissue to the orbital
      contents even after the absorbable materials have dissolved completely.
      Absorbable mesh plates could be another option for the reconstruction of the
      medial orbital wall.

PMID- 24286047
TI  - Role of muscle free flap in the salvage of complicated scalp wounds and infected
      prosthetic dura.
AB  - BACKGROUND: The prosthetic dura is an essential element in the protection of the
      cranial parenchyma and prevention of cerebrospinal fluid leakage. Although
      prosthetic dura are widely used in neurosurgery, they occasionally provoke
      infection, which can be a major concern after neurosurgical treatment. However,
      removal of the prosthetic dura carries a risk of brain parenchyma injury and
      cerebrospinal fluid leakage. The salvage of infected prosthetic dural material
      has not been adequately addressed in the literature. In this study, we
      demonstrate the value of the combination of a meticulous surgical debridement of
      necrotic tissue and simultaneous muscle free flap for intractable postoperative
      epidural abscess without removal of the infected prosthetic dura. METHODS:
      Between 2010 and 2012, we reviewed the data of 11 patients with persistent
      infection on the prosthetic dura. The epidural infections each occurred after a
      neurosurgical procedure, and there was soft tissue necrosis with the disclosure
      of the underlying prosthetic dura and dead bone around the scalp wound. To
      salvage the infected prosthetic dura, meticulous debridement and a muscle free
      flap were performed. RESULTS: All 11 patients experienced complete recovery from
      the complicated wound problem without the need for further surgical intervention.
      No signs of prosthetic dural infection were observed during the mean follow-up
      period of 11 months. CONCLUSIONS: The combination of a meticulous surgical
      debridement and coverage with a muscle free flap is an effective treatment for
      salvage of infected prosthetic dura.

PMID- 24286048
TI  - Reconstruction of the medial canthus using an ipsilateral paramedian forehead
      flap.
AB  - BACKGROUND: The medial canthus is an important area in determining the impression
      of a person's facial appearance. It is composed of various structures, including
      canthal tendons, lacrimal canaliculi, conjunctiva, the tarsal plate, and skin
      tissues. Due to its complexity, medial canthal defect reconstruction has been a
      challenging procedure to perform. The contralateral paramedian forehead flap is
      usually used for large defects; however, the bulkiness of the glabella and
      splitting at the distal end of the flap are factors that can reduce the rate of
      flap survival. We reconstructed medial canthal defects using ipsilateral
      paramedian forehead flaps, minimizing glabellar bulkiness. METHODS: This study
      included 10 patients who underwent medial canthal reconstruction using
      ipsilateral paramedian forehead flaps between 2010 and 2012. To avoid an acute
      curve of the pedicle, which can cause venous congestion, we attempted to make the
      arc of the pedicle rounder. Additionally, the pedicle was skeletonized from the
      nasal root to the glabella to reduce the bulkiness. RESULTS: All patients had
      basal cell carcinoma, and 3 of them had recurrent basal cell carcinoma. All of
      the flaps were successful without total or partial flap loss. Two patients
      developed venous congestion of the flap, which was healed using medicinal
      leeches. Four patients developed epiphora, and 2 patients developed telecanthus.
      CONCLUSIONS: Large defects of the medial canthus can be successfully
      reconstructed using ipsilateral paramedian forehead flaps. In addition, any
      accompanying venous congestion can be healed using medicinal leeches.

PMID- 24286049
TI  - Through-and-through Nasal Reconstruction with the Bi-Pedicled Forehead Flap.
AB  - BACKGROUND: Nasal reconstruction is one of the most difficult challenges for the
      head and neck surgeon, especially in the case of complex full thickness defects
      following malignant skin tumor resection. Full-thickness defects require
      demanding multi-step reconstruction. METHODS: Seven patients underwent surgical
      reconstruction of full-thickness nasal defects with a bi-pedicled forehead flap
      shaped appropriately to the defect. Patients were aged between 58 and 86 years,
      with a mean age of 63.4 years. All of the tumors were excised using traditional
      surgery, and in 4 of the patients, reconstruction was performed simultaneously
      following negativity of fresh frozen sections of the margins under general
      anesthesia. RESULTS: Nasal reconstruction was well accepted by all of the
      patients suffering non-melanoma skin tumors with acceptable cosmetic outcomes.
      The heart-shaped forehead flap was harvested in cases of subtotal involvement of
      the nasal pyramid, while smaller defects were reconstructed with a wing-shaped
      flap. No cartilaginous or osseous support was necessary. CONCLUSIONS: This bi
      pedicled forehead flap was a valid, versatile, and easy-to-implement alternative
      to microsurgery or multi-step reconstruction. The flap is the best indication for
      full-thickness nasal defects but can also be indicated for other complex facial
      defects in the orbital (exenteratio orbitae), zygomatic, and cheek area, for
      which the availability of a flap equipped with two thick and hairless lobes can
      be a valuable resource.

PMID- 24286050
TI  - Reconstruction of various perinasal defects using facial artery perforator-based
      nasolabial island flaps.
AB  - BACKGROUND: Classical flaps for perinasal defect reconstruction, such as forehead
      or nasolabial flaps, have some disadvantages involving limitations of the arc of
      rotation and two stages of surgery. However, a perforator-based flap is more
      versatile and allows freedom in flap design. We introduced our experience with
      reconstruction using a facial artery perforator-based propeller flap on the
      perinasal area. We describe the surgical differences between different defect
      subtypes. METHODS: Between December 2005 and August 2013, 10 patients underwent
      perinasal reconstruction in which a facial artery perforator-based flap was used.
      We divided the perinasal defects into types A and B, according to location. The
      operative results, including flap size, arc of rotation, complications, and
      characteristics of the perforator were evaluated by retrospective chart review
      and photographic evaluation. RESULTS: Eight patients were male and 2 patients
      were female. Their mean age was 61 years (range, 35-75 years). The size of the
      flap ranged from 1 cm*1.5 cm to 3 cm*6 cm. Eight patients healed uneventfully,
      but 2 patients presented with mild flap congestion. However, these 2 patients
      healed by conservative management without any additional surgery. All of the
      flaps survived completely with aesthetically pleasing results. CONCLUSIONS: The
      facial artery perforator-based flap allowed for versatile customized flaps, and
      the donor site scar was concealed using the natural nasolabial fold.

PMID- 24286051
TI  - A clinical anatomic study of internal mammary perforators as recipient vessels
      for breast reconstruction.
AB  - BACKGROUND: Partially resecting ribs of the recipient site to facilitate easy
      anastomosis of the internal mammary vessels to free flaps during breast
      reconstruction can cause chest wall pain or deformities. To avoid this, the
      intercostal perforating branches of the internal mammary vessels can be used for
      anastomosis. The purpose of this study was to investigate the location and size
      of the internal mammary perforator vessels based on clinical intraoperative
      findings and to determine their reliability as recipient vessels for breast
      reconstruction with microsurgical free tissue transfer. METHODS: Twelve patients
      were preoperatively screened for the presence of internal mammary perforators
      using Doppler tracing. After modified radical mastectomy was performed by a
      general surgeon, the location and size of the internal mammary perforator vessels
      were microscopically investigated. The external diameter was examined using a
      vessel-measuring gauge from a mechanical coupling device, and the distance from
      the mid-sternal line to the perforator was also measured. RESULTS: The largest
      arterial perforator averaged 1.5 mm, and the largest venous perforator averaged
      2.2 mm. Perforators emerging from the second intercostal space had the largest
      average external diameter; the second intercostal space also had the largest
      number of perforators arising from it. The average distance from the mid-sternal
      line to the perforator was 20.2 mm. CONCLUSIONS: Internal mammary perforators
      presented consistent and reliable anatomy in this study. Based on these results,
      the internal mammary perforators appear to have a suitable diameter for
      microvascular anastomosis and should be considered as an alternative recipient
      vessel to the internal mammary vessel.

PMID- 24286052
TI  - Correction of problematic hypospadias with dartos fascia-reinforced flap and
      slanted incision of fistula.
AB  - BACKGROUND: Hypospadias is the most common congenital malformation of the male
      urinary tract, wherein the urethral opening is located proximal to the normal
      site. Tubularized incised-plate urethroplasty reconstruction, and its efficacy,
      remains controversial due to the high recurrence rate. This study aimed to
      evaluate the results of dartos fascia-reinforced flap surgery in hypospadias
      patients with previous operative complications. METHODS: Nine patients (mean age,
      12 years) who had previous one- or two-stage repair with TIP urethroplasty and
      suffered from urethrocutaneous fistulas or fissures as complications, underwent
      dartos fascia-reinforced flap surgery in our clinic between January 2010 and
      December 2012. The mean postoperative follow-up period was 6 months. RESULTS:
      Among the 9 patients, 7 had complete correction. In all the patients, the maximum
      uroflow angle was >45 degrees . No patient complained of an unnatural urinating
      position. The patients and parents gave very high satisfaction scores (4.7
      points) with regard to the appearance of the outer genitalia. CONCLUSION: The
      dartos fascia-reinforced flap could be a useful and reliable option for
      complications of hypospadias repair or fissure with the prepuce preserved, given
      that histological aspects vary and that the possibility of recurrence in the
      glanular region is high.

PMID- 24286053
TI  - Comparative study of spiral oblique retinacular ligament reconstruction
      techniques using either a lateral band or a tendon graft.
AB  - BACKGROUND: In the management of mallet deformities, oblique retinacular ligament
      (ORL) reconstruction provides a mechanism for automatic distal interphalangeal
      (DIP) joint extension upon active proximal interphalangeal joint extension. The
      two variants of ORL reconstruction utilize either the lateral band or a free
      tendon graft. This study aims to compare these two surgical techniques and to
      assess any differences in functional outcome. As a secondary measure, the Mitek
      bone anchor and pull-in suture methods are compared. METHODS: A single
      institutional retrospective review of ORL reconstruction was performed. The
      standard patient demographics, injury mechanism, type of ORL reconstruction, and
      pre/postoperative degree of extension lag were collected for the 27 cases
      identified. The cases were divided into lateral band (group A, n=15) and free
      tendon graft groups (group B, n=12). Group B was subdivided into the pull-in
      suture technique (B-I) and the Mitek bone anchor method (B-II). RESULTS: Overall,
      ORL reconstructions had improved the mean DIP extension lag by 10 degrees 
      (P=0.027). Neither the reconstructive technique choice nor bone fixation method
      identified any statistically meaningful difference in functional outcome (P=0.51
      and P=0.83, respectively). Soft-tissue injury was associated with 30.8 degrees 
      of improvement in the extension lag. The most common complications were tendon
      adhesion and rupture. CONCLUSIONS: The choice of the ORL reconstructive technique
      or the bone anchor method did not influence the primary functional outcome of
      extension lag in this study. Both lateral band and free tendon graft ORL
      reconstructions are valid treatment methods in the management of chronic mallet
      deformity.

PMID- 24286054
TI  - Total maxillary reconstruction using a double-barreled and double skin paddle
      fibular flap after total maxillectomy.
AB  - Chondroblastomas are rare entities accounting for approximately 1% of all primary
      bone tumors. We describe a case of a 7-year-old girl with a giant chondroblastoma
      of the maxilla, treated with bilateral class III maxillectomy and reconstruction
      with a double-barreled and double skin paddle fibular free flap. We show evidence
      of an excellent aesthetic outcome at 6 months' follow up with no evidence of
      tumor recurrence. 

PMID- 24286055
TI  - Descended mouth corner: an ignored but needed feature of facial rejuvenation.
AB  - For years, the gold standard in facial rejuvenation has been the face lift.
      However, exploring new, less complex procedures for achieving the same goal is
      currently drawing interest. Rejuvenation of the perioral area is a difficult task
      for plastic surgeons because of the minimal effect that face lift procedures have
      over this region and the lack of published material on the subject. In this
      article, the descended mouth corner anguloplasty technique is presented. It is a
      20-minutes lift technique that can correct this typical feature of the ageing
      mouth. The authors have treated 71 patients using the technique with consistently
      good results, with just one requiring revision. They conclude that this procedure
      by itself and in combination with other small operations or even a full face lift
      can rejuvenate the ageing face. 

PMID- 24286056
TI  - Seroma reduction: using barbed sutures (v-loc) to close latissimus dorsi donor
      sites.

PMID- 24286057
TI  - Paraffinoma of the knee 60 years after primary injection.

PMID- 24286058
TI  - The Use of a Transparent Corneal Protector Permits Early Detection of Mydriasis
      to Prevent Blindness during Orbital Wall Fracture Surgery.

PMID- 24286059
TI  - Posttraumatic ectopic nail.

PMID- 24286060
TI  - A rare case of multifocal giant gell tumor of the tendon sheath involving both
      the hand and the foot.

PMID- 24286061
TI  - Correction of severe "pixie ear" deformity after rhytidectomy with modified
      minimal access cranial suspension lift.

PMID- 24286062
TI  - Gangnam style: celebrating a 30th anniversary and the 250th gangnam conference.

PMID- 24286063
TI  - Decentralized nursing education in Northern Norway: towards a sustainable
      recruitment and retention model in rural Arctic healthcare services.
AB  - INTRODUCTION: Decentralized nursing education (DNE) was established at Tromso
      University College in 1990 and has since become a part of the bachelor programme
      in nursing at UiT The Arctic University of Norway. The objective of the study was
      to investigate whether and to what degree the first DNE programme established in
      Norway has contributed to recruitment and retention of registered nurses (RNs) in
      rural healthcare services. METHODS: The quantitative survey took place in 2012. A
      questionnaire was distributed to 315 former students who had graduated from the
      DNE programme from 1994 to 2011. RESULTS: The primary finding of this study is
      that the DNE successfully recruits students from rural areas of Northern Norway.
      Nearly, 87.5% have their first employment in community healthcare services. They
      continued to work in the rural areas and 85% still worked as nurses in 2012. The
      DNE programme has been successful regarding recruitment and retention of RNs to
      community healthcare services. Fifty-six percent have attended a variety of
      postgraduate programmes. CONCLUSION: The DNE programme demonstrates itself as a
      successful study model regarding recruitment and retention of RNs to rural and
      remote areas.

PMID- 24286064
TI  - Posttraumatic Symptoms and Posttraumatic Growth of Israeli Firefighters, at One
      Month following the Carmel Fire Disaster.
AB  - Wildfire disasters are potentially traumatic events which directly and indirectly
      affect both citizens and first responders. The study of posttraumatic growth is
      scarcely found in the context of firefighters and only few studies have addressed
      this construct. In the current study, posttraumatic symptoms and posttraumatic
      growth were investigated among Israeli firefighters (N = 65), approximately one
      month after the Carmel Fire Disaster. Eight firefighters (12.3%) were found to be
      above the cut-off score for probable PTSD, with intrusion symptoms as the most
      frequent finding compared to avoidance and hyper-arousal symptoms. Posttraumatic
      growth (PTG) was evident to a small but considerable degree; noticeable changes
      were found regarding personal strength and appreciation of life. Results also
      revealed significant linear and quadratic relationships between PTSD and PTG.
      Results are discussed in light of past research on psychological responses among
      firefighters and first responders. 

PMID- 24286065
TI  - The Link between Peer Relations, Prosocial Behavior, and ODD/ADHD Symptoms in 7-9
      Year-Old Children.
AB  - Oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder
      (ADHD) are characterized by symptoms that hinder successful positive interaction
      with peers. The main goal of this study was to examine if the presence of
      symptoms of ODD and ADHD affects the relationship between positive social
      behavior and peer status found in 7-9-year-old children who show symptoms typical
      of ADHD and/or ODD. Furthermore, the possible interaction with sex was
      investigated. We used data collected in the first wave of The Bergen Child Study
      of mental health (BCS), a prospective longitudinal total population study of
      children's developmental and mental health. The target population consisted of
      children in the second to the fourth, in all public, private, and special schools
      in Bergen, Norway, in the fall of 2002 (N = 9430). All 79 primary schools in
      Bergen participated in the study. Both teacher (8809 complete cases) and parent
      (6253 complete cases) report were used in the analyses. ADHD and ODD scores were
      estimated using the Swanson Noland and Pelham rating scale version IV (SNAP-IV),
      and peer problems and prosocial behavior were assessed using the Strengths and
      Difficulties Questionnaire (SDQ). We replicated the relationship between peer
      problems and prosocial behavior found previously in typically developing
      children. Our results showed that the relationship between peer problems and
      prosocial behavior became weaker as the ODD symptoms increased in number and
      severity. For ADHD this effect was only found in the teacher report of the
      children. A sex effect for ODD symptoms was found only using the parent report:
      boys with ODD symptoms showed less prosocial behavior than girls with similar
      levels of ODD symptoms. Since this effect was not found using the teacher data,
      it may imply a situational effect (school/home) for girls with high levels of
      ODD. The moderator effect of ODD/ADHD was comparable for boys and girls. Our
      findings suggest that even if children with ADHD/ODD symptoms have the
      opportunity to practice their social skills in peer relationships, this is not
      necessarily accompanied by an increase in prosocial behavior. 

PMID- 24286066
TI  - Cognitive Performance in Men and Women Infected with HIV-1.
AB  - Introduction. Very few studies have examined the neuropsychological performance
      of HIV-positive women, and even fewer have attempted a comparison of cognitive
      functioning by gender. The aim of this study was to describe the nature of the
      neuropsychological performance of HIV seropositive patients by gender. Methods. A
      clinical sample made up of 151 subjects was recruited to participate in this
      study. All of the subjects underwent the same assessment process, consisting of a
      neuropsychological evaluation and an interview to gather sociodemographic,
      toxicological, and clinical data. Results and Discussion. Despite the fact that
      men obtained higher scores in visual memory, attention/psychomotor speed, and
      abstract reasoning/verbal intelligence, these differences were not statistically
      significant. In contrast, significant differences were found depending on
      subjects' serological status. Seropositive participants' neuropsychological
      performance was significantly lower than that of the seronegative participants in
      all of the areas assessed as follows: (1) visual memory; (2)
      attention/psychomotor speed; (3) abstract reasoning/verbal intelligence; (4)
      verbal memory for texts; (5) verbal memory for digits and words. Conclusions. The
      results from this study reveal no significant gender differences in the cognitive
      performance of patients infected with HIV-1. 

PMID- 24286067
TI  - Sociocultural context of suicidal behaviour in the sundarban region of India.
AB  - The role of mental illness in nonfatal deliberate self-harm (DSH) is
      controversial, especially in Asian countries. This prospective study examined the
      role of psychiatric disorders, underlying social and situational problems, and
      triggers of DSH in a sample of 89 patients hospitalised in primary care hospitals
      of the Sundarban Delta, India. Data were collected by using a specially designed
      DSH register, Explanatory Model Interview Catalogue (EMIC), and clinical
      interview. Psychiatric diagnosis was made following the DSM-IV guidelines. The
      majority of subjects were young females (74.2%) and married (65.2%). Most of them
      (69.7%) were uncertain about their "intention to die," and pesticide poisoning
      was the commonest method (95.5%). Significant male-female differences were found
      with respect to education level, occupation, and venue of the DSH attempt.
      Typical stressors were conflict with spouse, guardians, or in-laws, extramarital
      affairs, chronic physical illness, and failed love affairs. The major depressive
      disorder (14.6%) was the commonest psychiatric diagnosis followed by adjustment
      disorder (6.7%); however 60.7% of the cases had no psychiatric illness. Stressful
      life situations coupled with easy access to lethal pesticides stood as the risk
      factor. The sociocultural dynamics behind suicidal behaviour and community
      specific social stressors merit detailed assessment and timely psychosocial
      intervention. These findings will be helpful to design community-based mental
      health clinical services and community action in the region. 

PMID- 24286068
TI  - Social Psychiatry in the Waiting Room: What a Physician Can Learn about
      Occupational Stress from Workers Waiting to Be Examined.
AB  - Background. Work-related stress is a major problem for mental health. The
      occupational physician has the opportunity to gather information on the
      perception of stress from workers in the course of regular medical examinations.
      Method. 1,231 subjects, engaged in 6 different occupations, were invited to
      compile the Demand/Control/Support and the Effort/Reward/Imbalance
      questionnaires. Results. A specific profile of work-related stress emerged for
      each group of workers. Radiology physicians reported high control over work, but
      also exceedingly high demand and effort, high overcommitment, low social support,
      and low rewards from work. Health care workers were often overcommitted but had
      high levels of reward and social support. Low levels of social support and reward
      were recorded for mature workers, while special force policemen engaged in law
      enforcement during the G8 meeting had high levels of social support and regards,
      so that their resulting stress levels were closer to the reference group of
      employees in an insurance company with no front-office. Conclusion. The practice
      of administering questionnaires to groups of workers who are subject to medical
      surveillance is useful for monitoring mental health and well-being. 

PMID- 24286069
TI  - Association between Neurocognitive Impairment and the Short Allele of the 5-HTT
      Promoter Polymorphism in Depression: A Pilot Study.
AB  - Depression has been shown to be associated with cognitive deficits in various
      cognitive domains. However, it is still unclear which factors contribute to
      cognitive impairment. The objective of this study was to find out whether a
      functional polymorphism in the promoter region of the serotonin transporter (5
      HTTLPR) gene is associated with the impairment of cognitive functioning among
      depressed patients. In a pilot study, a sample of 19 patients with major
      depressive disorder (MDD) and 19 healthy controls was investigated with an
      extensive psychiatric and neuropsychological examination. All participants were
      genotyped for 5-HTTLPR. Depressed patients with the short allele of the 5-HTT
      promoter region exhibited inferior cognitive performance compared to patients
      with the long allele polymorphism. In healthy controls, no association between
      genotype and cognitive performance was found. The result suggests that in MDD
      patients with the short allele of the 5-HTTLPR polymorphism the vulnerability to
      cognitive impairment is increased compared to MDD patients without the short
      allele inheritance. These preliminary findings need to be confirmed in a larger
      cohort of MDD patients. 

PMID- 24286070
TI  - Influence of sleep disturbances on quality of life of Iranian menopausal women.
AB  - Background. Subjective sleep disturbances increase during menopause. Some
      problems commonly encountered during menopause, such as hot flushes and sweating
      at night, can cause women to have difficulty in sleeping. These complaints can
      influence quality of life of menopausal women. Methods. This cross-sectional
      study was performed on menopausal women attending health centers in Qazvin for
      periodic assessments. We measured excessive daytime sleepiness by Epworth
      sleepiness scale (ESS), obstructive sleep apnea (OSA) by the Berlin
      questionnaire, and insomnia by the insomnia severity index (ISI). We evaluate
      quality of life by the Menopause specific quality of life questionnaire (MENQOL).
      Results. A total of 380 menopausal women entered the study. Mean age of
      participated women was 57.6 +/- 6.02. Mean duration of menopause was 6.3 +/- 4.6.
      The frequency of severe and moderate insomnia was 8.4% (32) and 11.8% (45).
      Severe daytime sleepiness (ESS >= 10) was present in 27.9% (80) of the
      participants. Multivariate analytic results show that insomnia and daytime
      sleepiness have independent negative impact on each domain and total score of
      MENQOL questionnaire. Conclusion. According to our findings, EDS and insomnia are
      frequent in menopausal women. Both EDS and insomnia have significant quality of
      life impairment. 

PMID- 24286071
TI  - Effects of cryotherapy on the maxillary antrostomy patency in a rabbit model of
      chronic rhinosinusitis.
AB  - It is acknowledged that many causes of failures in endoscopic sinus surgery are
      related to scarring and narrowing of the maxillary antrostomy. We assessed the
      effect of low-pressure spray cryotherapy in preventing the maxillary antrostomy
      stenosis in a chronic rhinosinusitis (CRS) rabbit model. A controlled,
      randomized, double-blind study was conducted on 22 New Zealand rabbits. After
      inducing unilateral rhinogenic CRS, a maxillary antrostomy was performed and
      spray cryotherapy was employed on randomly selected 12 rabbits, while saline
      solution was applied to the control group (n = 10). The antrostomy dimensions and
      the histological scores were assessed 4 weeks postoperatively. The diameter of
      cryotreated antrostomy was significantly larger at 4 weeks than that in the
      control group. At 4 weeks, the maxillary antrostomy area in the study group was
      significantly larger than the mean area in the control group (103.92 +/- 30.39
      mm2 versus 61.62 +/- 28.35 mm2, P = 0.002). Submucosal fibrous tissues and
      leukocytic infiltration in saline-treated ostia were more prominent than those in
      cryotreated ostia with no significant differences between the two groups
      regarding the histological scores. Intraoperative low-pressure spray cryotherapy
      increases the patency of the maxillary antrostomy at 4 weeks postoperatively with
      no important local side effects.

PMID- 24286072
TI  - Interpretation of C-reactive protein concentrations in critically ill patients.
AB  - Infection is often difficult to recognize in critically ill patients because of
      the marked coexisting inflammatory process. Lack of early recognition prevents
      timely resuscitation and effective antimicrobial therapy, resulting in increased
      morbidity and mortality. Measurement of a biomarker, such as C-reactive protein
      (CRP) concentration, in addition to history and physical signs, could facilitate
      diagnosis. Although frequently measured in clinical practice, few studies have
      reported on the pathophysiological role of this biomarker and its predictive
      value in critically ill patients. In this review, we discuss the
      pathophysiological role of CRP and its potential interpretation in the
      inflammatory processes observed in critically ill patients. 

PMID- 24286074
TI  - Over, and underexpression of endothelin 1 and TGF-beta family ligands and
      receptors in lung tissue of broilers with pulmonary hypertension.
AB  - Transforming growth factor beta (TGF beta ) is a family of genes that play a key
      role in mediating tissue remodeling in various forms of acute and chronic lung
      disease. In order to assess their role on pulmonary hypertension in broilers, we
      determined mRNA expression of genes of the TGF beta family and endothelin 1 in
      lung samples from 4-week-old chickens raised either under normal or cold
      temperature conditions. Both in control and cold-treated groups of broilers,
      endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher
      than levels from healthy birds (P < 0.05), whereas levels in animals with cardiac
      failure were intermediate. Conversely, TGF beta 2 and TGF beta 3 gene expression
      in lungs were higher in healthy animals than in ascitic animals in both groups (P
      < 0.05). TGF beta 1, T beta RI, and T beta RII mRNA gene expression among
      healthy, ascitic, and chickens with cardiac failure showed no differences (P >
      0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the
      control group as compared with the values from healthy birds (P < 0.05). 

PMID- 24286075
TI  - Acute and chronic oral toxicity of a partially purified plaunotol extract from
      Croton stellatopilosus Ohba.
AB  - Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer
      properties, has been commercially isolated from leaves of Croton stellatopilosus
      Ohba. This Thai medicinal plant was traditionally used in the form of crude
      extracts, suggesting that it is possible to administer these plaunotol-containing
      extracts without toxicity. To confirm its safety, the oral toxicity of a
      partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was
      simply prepared by 95% ethanol reflux extraction followed by hexane partition.
      The obtained extract was analyzed and found to contain 43% w/w of plaunotol and
      another compound, likely a fatty acid-plaunotol conjugate that is considered a
      major impurity. Oral administration of PPE to ICR mice and Wistar rats was
      conducted to evaluate acute and chronic toxicity of the plaunotol extract,
      respectively. The acute toxicity study demonstrated that PPE was practically
      nontoxic based on its high median lethal dose value (LD50 = 10.25 g/kg). The
      chronic toxicity studies also showed the absence of mortality and clinical
      symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month
      period. Histopathological and hematological analyses revealed that altered liver
      and kidney function and increased blood platelet number, but only at the high
      doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe
      for further development as a therapeutic agent in humans.

PMID- 24286073
TI  - Psychomotor retardation in depression: a systematic review of diagnostic,
      pathophysiologic, and therapeutic implications.
AB  - Psychomotor retardation is a central feature of depression which includes motor
      and cognitive impairments. Effective management may be useful to improve the
      classification of depressive subtypes and treatment selection, as well as
      prediction of outcome in patients with depression. The aim of this paper was to
      review the current status of knowledge regarding psychomotor retardation in
      depression, in order to clarify its role in the diagnostic management of mood
      disorders. Retardation modifies all the actions of the individual, including
      motility, mental activity, and speech. Objective assessments can highlight the
      diagnostic importance of psychomotor retardation, especially in melancholic and
      bipolar depression. Psychomotor retardation is also related to depression
      severity and therapeutic change and could be considered a good criterion for the
      prediction of therapeutic effect. The neurobiological process underlying the
      inhibition of activity includes functional deficits in the prefrontal cortex and
      abnormalities in dopamine neurotransmission. Future investigations of psychomotor
      retardation should help improve the understanding of the pathophysiological
      mechanisms underlying mood disorders and contribute to improving their
      therapeutic management. 

PMID- 24286076
TI  - UGT1A1 gene mutation due to Crigler-Najjar syndrome in Iranian patients:
      identification of a novel mutation.
AB  - Crigler-Najjar syndrome (CNS) type I and type II are inherited as autosomal
      recessive conditions that are caused by mutations in the UGT1A1 gene. We present
      the analysis of UGT1A1 gene in 12 individuals from three different families. This
      analysis allowed us to identify one novel mutation, which was not previously
      described. In this study, three families with clinically diagnosed CNS referred
      from Khuzestan province, southwest Iran, were screened. After signing the
      informed consent, peripheral blood samples from the patients and their parents
      were collected in EDTA-containing tube followed by DNA extraction using a routine
      phenol-chloroform method. All five coding exons and the flanking intronic regions
      of the bilirubin-UGT were amplified by polymerase chain reaction (PCR) followed
      by DNA sequencing by Sanger method. From the first family, a 9-month-old boy was
      homozygous for a deletion mutation of two adjacent nucleotides including one
      adenosine (A) and one glutamine (G) between nucleotides 238 and 239 in exon 1
      (c.238_240 del AG). In the second family, there were two affected individuals, an
      11-year-old girl and a fetus, found to be homozygous for the same mutation. The
      third family showed a mutation at nucleotide 479 in exon 1 (Val160Glu) that has
      been reported previously. Molecular analysis can significantly help confirm the
      diagnosis of CNS, without any need for the liver biopsy, and may help the
      therapeutic management by ruling out more harmful causes of hyperbilirubinemia. 

PMID- 24286078
TI  - Environmental contaminants in hospital settings and progress in disinfecting
      techniques.
AB  - Medical devices, such as stethoscopes, and other objects found in hospital, such
      as computer keyboards and telephone handsets, may be reservoirs of bacteria for
      healthcare-associated infections. In this cross-over study involving an Italian
      teaching hospital we evaluated microbial contamination (total bacterial count
      (TBC) at 36 degrees C/22 degrees C, Staphylococcus spp., moulds, Enterococcus
      spp., Pseudomonas spp., E. coli, total coliform bacteria, Acinetobacter spp., and
      Clostridium difficile) of these devices before and after cleaning and differences
      in contamination between hospital units and between stethoscopes and keyboards
      plus handsets. We analysed 37 telephone handsets, 27 computer keyboards, and 35
      stethoscopes, comparing their contamination in four hospital units. Wilcoxon
      signed-rank and Mann-Whitney tests were used. Before cleaning, many samples were
      positive for Staphylococcus spp. and coliforms. After cleaning, CFUs decreased to
      zero in most comparisons. The first aid unit had the highest and intensive care
      the lowest contamination (P < 0.01). Keyboards and handsets had higher TBC at 22
      degrees C (P = 0.046) and mould contamination (P = 0.002) than stethoscopes.
      Healthcare professionals should disinfect stethoscopes and other possible sources
      of bacterial healthcare-associated infections. The cleaning technique used was
      effective in reducing bacterial contamination. Units with high patient turnover,
      such as first aid, should practise stricter hygiene. 

PMID- 24286077
TI  - Efficient hepatic delivery of drugs: novel strategies and their significance.
AB  - Liver is a vital organ responsible for plethora of functions including
      detoxification, protein synthesis, and the production of biochemicals necessary
      for the sustenance of life. Therefore, patients with chronic liver diseases such
      as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate
      attention to sustain life and as a result are often exposed to the prolonged
      treatment with drugs/herbal medications. Lack of site-specific delivery of these
      medications to the hepatocytes/nonparenchymal cells and adverse effects
      associated with their off-target interactions limit their continuous use. This
      calls for the development and fabrication of targeted delivery systems which can
      deliver the drug payload at the desired site of action for defined period of
      time. The primary aim of drug targeting is to manipulate the whole body
      distribution of drugs, that is, to prevent distribution to non-target cells and
      concomitantly increase the drug concentration at the targeted site. Carrier
      molecules are designed for their selective cellular uptake, taking advantage of
      specific receptors or binding sites present on the surface membrane of the target
      cell. In this review, various aspects of liver targeting of drug molecules and
      herbal medications have been discussed which elucidate the importance of
      delivering the drugs/herbal medications at their desired site of action. 

PMID- 24286079
TI  - Strategies for imaging androgen receptor signaling pathway in prostate cancer:
      implications for hormonal manipulation and radiation treatment.
AB  - Prostate cancer (Pca) is a heterogeneous disease; its etiology appears to be
      related to genetic and epigenetic factors. Radiotherapy and hormone manipulation
      are effective treatments, but many tumors will progress despite these treatments.
      Molecular imaging provides novel opportunities for image-guided optimization and
      management of these treatment modalities. Here we reviewed the advances in
      targeted imaging of key biomarkers of androgen receptor signaling pathways. A
      computerized search was performed to identify all relevant studies in Medline up
      to 2013. There are well-known limitations and inaccuracies of current imaging
      approaches for monitoring biological changes governing tumor progression. The
      close integration of molecular biology and clinical imaging could ease the
      development of new molecular imaging agents providing novel tools to monitor a
      number of biological events that, until a few years ago, were studied by
      conventional molecular assays. Advances in translational research may represent
      the next step in improving the oncological outcome of men with Pca who remain at
      high risk for systemic failure. This aim may be obtained by combining the
      anatomical properties of conventional imaging modalities with biological
      information to better predict tumor response to conventional treatments. 

PMID- 24286080
TI  - Does the adult human ciliary body epithelium contain "true" retinal stem cells?
AB  - Recent reports of retinal stem cells being present in several locations of the
      adult eye have sparked great hopes that they may be used to treat the millions of
      people worldwide who suffer from blindness as a result of retinal disease or
      injury. A population of proliferative cells derived from the ciliary body
      epithelium (CE) has been considered one of the prime stem cell candidates, and as
      such they have received much attention in recent years. However, the true nature
      of these cells in the adult human eye has still not been fully elucidated, and
      the stem cell claim has become increasingly controversial in light of new and
      conflicting reports. In this paper, we will try to answer the question of whether
      the available evidence is strong enough for the research community to conclude
      that the adult human CE indeed harbors stem cells. 

PMID- 24286081
TI  - Novel poly(L-lactide-co-epsilon-caprolactone) matrices obtained with the use of
      Zr[Acac]4 as nontoxic initiator for long-term release of immunosuppressive drugs.
AB  - Slowly degradable copolymers of L-lactide and epsilon-caprolactone can provide
      long-term delivery and may be interesting as alternative release systems of
      cyclosporine A (CyA) and rapamycin (sirolimus), in which available dosage forms
      cause a lot of side effects. The aim of this study was to obtain slowly
      degradable matrices containing immunosuppressive drug from PLACL initiated by
      nontoxic Zr[Acac]4. Three kinds of poly(L-lactide-co-epsilon-caprolactone)
      (PLACL) matrices with different copolymer chain microstructure were used to
      compare the release process of cyclosporine A and rapamycine. The influence of
      copolymer chain microstructure on drug release rate and profile was also
      analyzed. The determined parameters could be used to tailor drug release by
      synthesis of demanded polymeric drug carrier. The studied copolymers were
      characterized at the beginning and during the degradation process of the
      polymeric matrices by NMR spectroscopy, GPC (gel permeation chromatography), and
      DSC (differential scanning calorimetry). Different drug release profiles have
      been observed from each kind of copolymer. The correlation between drug release
      process and changes of copolymer microstructure during degradation process was
      noticed. It was determined that different copolymer composition (e.g., lower
      amount of caprolactone units) does not have to influence the drug release, but
      even small changes in copolymer randomness affect this process.

PMID- 24286083
TI  - The influence of cigarette smoking on gingival bleeding and serum concentrations
      of haptoglobin and alpha 1-antitrypsin.
AB  - The objectives of this study were to evaluate the influence of cigarette smoking
      on gingival bleeding and serum concentrations of cotinine, haptoglobin, and alpha
      1-antitrypsin in Malaysian smokers. A total of 197 male smokers and nonsmokers
      were recruited for this study. Plaque index, bleeding on probing (BOP), and
      levels of serum cotinine, haptoglobin, and alpha 1-antitrypsin were evaluated.
      The data were analyzed using SPSS version 20.0, with the significance level set
      at alpha <= 0.05. Linear regression analyses were performed. The mean cigarette
      consumption per day was 13.39 +/- 5.75 cigarettes; the mean duration was 16.03 +/
      8.78 years. Relatively low BOP values (26.05 +/- 1.48) and moderate plaque
      indexes (51.35 +/- 11.27) were found. The levels of serum cotinine (106.9 +/-
      30.71 ng/dL), haptoglobin (76.04 +/- 52.48 mg/dL), and alpha 1-antitrypsin
      (141.90 +/- 18.40 mg/dL) were significantly higher in smokers compared to non
      smokers. Multiple logistic regression models for all variables and smokers
      demonstrated observed differences between BOP, the number of cigarettes per day,
      and duration of smoking, while serum cotinine, haptoglobin and alpha-1
      antitrypsin levels showed no significant differences. Duration of smoking (years)
      and the cotinine level in serum showed a significant correlation with plaque
      index. The present analysis demonstrated that the duration of smoking in years,
      but not the number of cigarettes smoked per day, was associated with reduced
      gingival bleeding in smokers. 

PMID- 24286082
TI  - Epigenetic modifications and diabetic retinopathy.
AB  - Diabetic retinopathy remains one of the most debilitating chronic complications,
      but despite extensive research in the field, the exact mechanism(s) responsible
      for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways
      have been implicated in its development, and genes associated with these pathways
      are altered. Diabetic environment also facilitates epigenetics modifications,
      which can alter the gene expression without permanent changes in DNA sequence.
      The role of epigenetics in diabetic retinopathy is now an emerging area, and
      recent work has shown that genes encoding mitochondrial superoxide dismutase
      (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified,
      activates of epigenetic modification enzymes, histone lysine demethylase 1
      (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible
      for regulating nuclear transcriptional factor and VEGF are upregulated. With the
      growing evidence of epigenetic modifications in diabetic retinopathy, better
      understanding of these modifications has potential to identify novel targets to
      inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted
      towards histone modification, DNA methylation, and miRNAs are now being tried for
      cancer and other chronic diseases, and better understanding of the role of
      epigenetics in diabetic retinopathy will open the door for their possible use in
      combating this blinding disease. 

PMID- 24286084
TI  - Molecular characterization and in silico analysis of naturally occurring TEM beta
      lactamase variants among pathogenic Enterobacteriaceae infecting Indian patients.
AB  - Cephalosporin resistance, particularly due to bla(TEM) encoded beta-lactamases,
      among Enterobacteriaceae is, though, an increasing public health problem in
      India; their circulating genetic variants remain unknown. The present study deals
      with determination of bla(TEM) variants among 134 pathogenic Enterobacteriaceae
      of Indian origin. Their resistance profile against 3rd generation cephalosporins
      was determined. The presence of bla(TEM) variants among the bacterial plasmids
      was characterized by PCR followed by sequencing. Intergenic relations among the
      variants was determined by phylogenetic analysis. bla(TEM) protein were modeled
      by Modeller9v5 and verified. The catalytic pockets were characterized, and their
      interaction with cephalosporins was analyzed using AutoDock tools. More than 87%
      of isolates showed cephalosporin resistance with ESBL production among 57.8% of
      Escherichia coli and 50.6% of klebsiella pneumoniae. bla(TEM-1) (84.21%), bla(TEM
      1) like (3.94%), bla(TEM-33) (3.94%), bla(TEM-116) (3.94%), bla(TEM-169) (3.94%),
      and bla(TEM-190) (7.89%) were detected in 76 isolates. Four variants, namely,
      bla(TEM-1) like, bla(TEM-33), bla(TEM-169), and bla(TEM-190), coexisted in 3
      isolates. The largest catalytic pocket of bla(TEM-33) explained its expanded
      activity towards beta-lactam-beta-lactamase inhibitor combinations. Molecular
      docking indicated differential resistance pattern of bla(TEM) variants.

PMID- 24286085
TI  - Molecular identification and polymorphism determination of cutaneous and visceral
      leishmaniasis agents isolated from human and animal hosts in Iran.
AB  - Amplification of internal transcript spacer 1 of ribosomal RNA (ITS1-RNA) gene
      followed by RFLP analysis and sequencing was used to identify the causing agents
      of cutaneous and visceral leishmaniasis (CL and VL) in humans and animal
      reservoir hosts from various geographical areas in Iran. We also used random
      amplified polymorphic DNA (RAPD-PCR) to obtain polymorphisms among isolates of
      Leishmania spp. Totally, 362 suspected human and animal cases including 173 CL,
      49 VL, 60 rodents, and 80 domestic dogs were examined for Leishmania infection.
      From 112 culture-positive samples prepared from CL cases, 75 (67%) were infected
      with L. major and 37 (33%) with L. tropica. Of the 60 rodents examined, 25
      (41.6%) harbored the Leishmania infection; 21 were infected with L. major and 4
      with L. turanica. From 49 suspected VL, 29 were positive by direct agglutination
      test (DAT), whereas microscopy detected parasite in bone marrow of 25 and culture
      in 28 of the patients. Two VL patients were infected with L. tropica and 26 with
      L. infantum. Of the 80 domestic dogs, 56 showed anti-Leishmania antibodies with
      DAT. Of these, 55 were positive by both microscopy and culture. Molecular
      identity, obtained only for 47 samples, revealed L. infantum in 43 and L. tropica
      in 4 dogs. The polymorphisms among L. tropica and L. major isolates were 3.6% and
      7.3%; the rate among human and canine VL isolates was 2.8% and 9.8%,
      respectively. Our results showed that at least four different Leishmania species
      with various polymorphisms circulate among humans and animal hosts in Iran. 

PMID- 24286087
TI  - Ultrasonography of the infant hip.

PMID- 24286088
TI  - Contrast enhanced ultrasound and magnetic resonance imaging in hepatocellular
      carcinoma diagnosis.
AB  - BACKGROUND: The new developments in imaging technology, including contrast
      enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance
      imaging (MRI), allow a better diagnosis of both malignant and benign liver
      lesions. MATERIAL AND METHODS: A retrospective trial of 126 patients was
      conducted in the Gastroenterology and Imaging Departments of the University of
      Medicine and Pharmacy Craiova, Romania. CEUS and MRI were the imaging techniques
      used for diagnosis of focal liver lesions (FLL), especially for hepatocellular
      carcinoma (HCC). Histopathology was used only in 15 cases. For each method of
      investigation we calculated the sensitivity, specificity, positive and negative
      predictive values (PPV and NPV), positive and negative likelihood ratio (+LR, 
      LR), accuracy and we compared the ROC curves. Statistical analysis also included
      the Chi-square and Kappa tests. RESULTS: Seventy six cases were diagnosed as HCC,
      with average size of 5.2+/-3.3 cm in diameter. The sensitivity and specificity
      were 71.4% and 95.6% for CEUS and 91.4%, 98.9% respectively, for MRI. When
      comparing the ROC curves, we found a higher area under curve for MRI (0.952) then
      for CEUS (0.835) (p=0.005), and 95% confidence interval of 0.0343 to 0.199. No
      statistically significant difference in diagnosis of FLL was found between CEUS
      and MRI (p > 0.05) and the agreement between the two imaging techniques was good
      (k = 0.78). CONCLUSIONS: CEUS can be used as the first step in the diagnosis of
      liver lesions, but MRI remains the gold standard diagnostic method for liver
      tumors.

PMID- 24286090
TI  - Evaluation of effects of Extracorporeal Shock Wave Lithotripsy on renal
      vasculature with Doppler ultrasonography.
AB  - OBJECTIVES: In this prospective study, we aimed to demonstrate the effects of
      Extracorporeal Shock Wave Lithotripsy (ESWL) on renal blood flow in patients
      treated for renal/ ureteral stones. MATERIAL AND METHODS: The study group
      comprised 41 patients (26 males, 15 females, aged between 18-63 years, mean age
      45 years), 23 with renal and 18 with ureteral stones, who underwent ESWL between
      March 2010 and January 2011. Colour Doppler ultrasonography and pulsed wave
      spectral analysis was performed before, 1 hour, and 7 days after ESWL to both
      ipsilateral and contralateral kidneys in order to measure resistive index (RI),
      pulsatility index (PI) and acceleration time (AT) values. RESULTS: One hour after
      ESWL, RI and PI values showed significant increase from pre-ESWL values in both
      ipsilateral and contralateral kidneys. However, no significant change was found
      in AT values. Seven days after ESWL, PI in both ipsilateral and contralateral
      kidneys and RI in contralateral kidney returned to pre-ESWL values. But, 7 days
      after ESWL, RI in the ipsilateral kidney did not return to pre-ESWL values,
      although decrease in RI values were observed. CONCLUSION: Spectral Doppler
      analysis can provide valuable information as a non-invasive method to assess the
      hemodynamic changes and renal microcirculation status in cases managed with ESWL.

PMID- 24286089
TI  - How many measurements are needed for liver stiffness assessment by 2D-Shear Wave
      Elastography (2D-SWE) and which value should be used: the mean or median?
AB  - AIM: To analyze how many measurements are needed for non-invasive assessment of
      liver stiffness (LS) by means of 2D-Shear Wave Elastography (2D-SWE) and if the
      use of mean of median values of 2D-SWE measurements is needed. METHODS: We
      evaluated 449 consecutive subjects (with or without chronic liver disease) by
      means of Transient Elastography (TE) and 2D-SWE. We compared the correlation of
      LS assessed by TE with 2D-SWE measurements when using either the median of 5
      valid 2D-SWE measurements or the mean of 3 or 5 valid 2D-SWE measurements.
      RESULTS: We obtained reliable LS measurements by TE in 330/449 subjects (73.5%).
      From these, in 281 subjects we obtained 5 valid 2D-SWE measurements. The
      correlation of LS assessed by TE with 2D-SWE values was similar when we used the
      median value of 5 valid 2D-SWE measurements, the mean value of 5 valid 2D-SWE
      measurements or the mean value of 3 valid 2D-SWE measurements: r =0.683, r=0.711
      and r=0.691, respectively. There were no significant differences between the
      median value of 5 valid 2D-SWE measurements; the mean value of 5 valid 2D-SWE
      measurements; or the mean value of 3 valid 2D-SWE measurements: 7.6 kPa, 7.7 kPa
      and 7.6 kPa, respectively. CONCLUSIONS: Our study showed that it is enough to
      perform 3 valid 2D-SWE measurements and to use the mean value of these
      measurements.

PMID- 24286091
TI  - The learning curve of real time elastosonography: a preliminary study conducted
      for the assessment of malignancy risk in thyroid nodules.
AB  - BACKGROUND: Malignancy is correlated with stiffness which is assessed by real
      time elastosonography (RTE). RTE is not used in routine practice. We aimed to
      establish the learning curve of RTE on radiology residents. METHODS: Forty >/=1
      cm solitary thyroid nodules referred to fine needle aspiration cytology were
      examined with RTE by a radiology specialist and two radiology residents
      separately. Patients with malignant and undetermined FNAC findings underwent
      surgery. Strain ratio and elasticity score results of the radiology residents
      were compared to the results of the radiology specialist taking the
      histopathology results as the reference. To establish the learning curve and
      compare the diagnostic accuracy of residents, Receiver Operating Characteric
      curves were generated and Area Under the Curve were calculated. RESULTS: Thirty
      four nodules were benign and the others were malignant. The radiology specialist
      had a very high correct class prediction for the differentiation of benign versus
      malignant thyroid nodules. Statistical analysis of the strain ratio measurements
      showed that one of the residents had similar results with the radiology
      specialist after the seventh patient and the other one after the fourth patient.
      On the other hand the elasticity score measurements of all examiners had low
      correct class prediction. CONCLUSYONS: Strain ratio measurement by RTE is an
      easily learned sonographic method that can assist in the evaluation of benign
      versus malignant nature of the lesions. However, interpretation of the elasticity
      scores requires more expertise. The results of this preliminary study need to be
      verified with a larger sample population.

PMID- 24286092
TI  - Assessment of color Doppler ultrasonography findings in gynecomastia.
AB  - AIM: To evaluate the color Doppler ultrasound (US) findings of gynecomastia and
      compare them with sonographic Tanner staging to determine an additional
      diagnostic tool. PATIENTS AND METHODS: Eighteen male (mean age 13.87 +/- 1.72)
      patients (36 breasts) with breast enlargement were examined with gray-scale and
      color Doppler ultrasound (US), and these were used to determine the Tanner
      stages. In addition, the arterial and venous flow scores were assessed. The
      resistivity index (RI) values were also measured at the medial, lateral, and
      retroareolar regions of the breasts, and the mean RI values for each breast were
      then calculated. RESULTS: Gynecomastia was detected in 30 breasts, and the mean
      retroareolar thickness was 8.03 mm. Furthermore, arterial and venous flows were
      detected in 73.3% and 56.7% of the breasts, respectively. However, there was no
      correlation between the arterial and venous flows and the retroareolar glandular
      tissue thickness. The average of the mean RI values of the three regions of the
      breast was 0.62, and there was a statistically significantly positive correlation
      between the mean RI values of the breasts and the Tanner stages as established by
      US. Furthermore, there was a strongly significant positive correlation between
      the arterial and venous flow scores and the Tanner stages. CONCLUSIONS: Our
      research indicates that vascularity is correlated with breast development in
      patients with gynecomastia. Additionally, we determined that RI values might be
      as important as Tanner stages on US.

PMID- 24286093
TI  - Solid parotid tumors: an individual and integrative analysis of various
      ultrasonographic criteria. A prospective and observational study.
AB  - OBJECTIVES: The purpose of the study is to identify and validate ultrasound
      criteria for parotid tumors evaluation, as well as to elaborate a multimodal,
      multi-criteria and integrative ultrasound approach for allowing tumor
      discrimination in a non-invasive manner. MATERIAL AND METHOD: Twenty patients
      with solid parotid tumors (12 benign, 8 malignant) were examined by ultrasound:
      real-time "grey scale" ultrasound, Doppler ultrasound, elastography, harmonic
      ultrasound imaging with i.v. contrast (CEUS). The study focused on tumor
      morphology and circulation. The analysis of the results was observational,
      enhanced by statistical methods and artificial intelligence (decision trees).
      RESULTS: All malignant tumors showed increased hypoechogenicity, tumoral cervical
      adenopathies, increased stiffness and "in block" mobility with the parotid gland
      upon palpation with the transducer, uneven distribution of the contrast material
      during the arterial phase (8/8). To varying degrees, they showed imprecise
      delineation (7/8), structural heterogeneity (6/8) and disorganized flow pattern
      (6/8). All cases of benign tumors showed heterogeneous echostructure, clear
      delineation and no capsule (12). They also showed moderate hypoechogenicity
      (9/12), no cervical lymph nodes (11/12) and variable rigidity (increased 6/12;
      low 3/12). A selection and ranking of relevant ultrasound parameters was also
      made. Some of them were included in a transparent and easy-to-use decision tree
      model with 100% data accuracy. CONCLUSIONS: The characterization and
      discrimination of solid parotid tumors require a multimodal and multicriteria
      approach. Ultrasound criteria can be divided into criteria of certainty and
      criteria of diagnosis probability. CEUS examination of parotid tumors did not
      reveal significant differences between benign and malignant circulatory bed.
      Decision trees discovered by artificial intelligence from the data may represent
      intelligent diagnosis support systems with very high accuracy, up to 100%.

PMID- 24286086
TI  - Animal models of diabetic retinopathy: summary and comparison.
AB  - Diabetic retinopathy (DR) is a microvascular complication associated with chronic
      exposure to hyperglycemia and is a major cause of blindness worldwide. Although
      clinical assessment and retinal autopsy of diabetic patients provide information
      on the features and progression of DR, its underlying pathophysiological
      mechanism cannot be deduced. In order to have a better understanding of the
      development of DR at the molecular and cellular levels, a variety of animal
      models have been developed. They include pharmacological induction of
      hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis
      without diabetes (to compensate for the absence of proliferative DR symptoms). In
      this review, we summarize the existing protocols to induce diabetes using STZ. We
      also describe and compare the pathological presentations, in both morphological
      and functional aspects, of the currently available DR animal models. The
      advantages and disadvantages of using different animals, ranging from zebrafish,
      rodents to other higher-order mammals, are also discussed. Until now, there is no
      single model that displays all the clinical features of DR as seen in human. Yet,
      with the understanding of the pathological findings in these animal models,
      researchers can select the most suitable models for mechanistic studies or drug
      screening. 

PMID- 24286094
TI  - Hip sonography update. Quality-management, catastrophes - tips and tricks.
AB  - AIM: Hip sonography is today considered to be the diagnostic standard tool for
      developmental dysplasia of the hip (DDH) diagnosis. In Germany special
      commissions control the quality of the sonograms according to checklists to keep
      the standard high and to avoid over- and under - treatment. This paper lists tips
      and tricks to avoid typical mistakes according to these results. MATERIAL AND
      METHOD: In 8 German countries the quality of sonograms used to diagnose DDH was
      checked according to special checklists. An additional 250 medical doctors
      (pediatricians, radiologists, orthopaedic surgeons) were asked to classify 4
      sonograms by measuring and typing. From the same group the projection (standing
      left, standing right, horizontal-cranial left, horizontal-cranial right) was
      checked according to the correct diagnosis in the shortest time. RESULTS: In 1.6
      % - 43.7% the licence for hip sonography was withdrawn by the German commission.
      The best projection with the lowest rate of wrong interpretation was the
      "standing right"-projection. Most of the mistakes were made because of a wrong
      anatomical identification and usability check. CONCLUSION: Hip sonography must be
      trained by authorized teachers. The quality of the sonograms must be controlled
      according to checklists. The bedside teaching without control leads to a
      systematic teaching of mistakes and finally catastrophes.

PMID- 24286095
TI  - Liver elastography - an update.
AB  - Liver fibrosis evaluation is very important for treatment and prognosis in
      patients with chronic liver disease. The "gold-standard" method for liver
      fibrosis assessment is still considered to be the liver biopsy, but in the last
      years non-invasive methods have increasingly been used, especially ultrasound
      based elastographic ones. The oldest and the only validated elastographic method
      for non-invasive liver fibrosis evaluation is Transient Elastography (TE). In the
      last 2-3 years, similar results to TE for liver fibrosis assessment were obtained
      by using Acoustic Radiation Force Impulse (ARFI) Elastography. More recently,
      Real Time Shear Wave Elastography (SWE) was developed and promising results were
      obtained by this technique. Strain elastography is less used in clinical practice
      for non-invasive liver fibrosis assessment. TE is also useful for predicting
      liver cirrhosis complications, especially portal hypertension. ARFI elastography
      seems to be inferior to TE in this field. 

PMID- 24286096
TI  - Large spectrum of complete urinary collecting system duplication exemplified by
      cases. Pictorial essay.
AB  - Urinary collecting system duplication is a congenital anomaly and can associate
      various types of urinary tract pathologies. Authors will illustrate by cases some
      of associated anomalies such as ureterocele, extravesical ectopic ureter,
      vesicoureteral reflux or reflux nephropathy; one case presented an association
      between posterior urethral valve and bilateral collecting system duplication. 

PMID- 24286097
TI  - A case of alkaptonuria - ultrasonographic findings.
AB  - Alkaptonuria is a rare disease with autosomal recessive inheritance and variable
      expression. The weight-bearing joint involvement and spondylitis-like vertebral
      changes occur only after the 3rd decade. Musculoskeletal ultrasonographic
      findings in alkaptonuria were only rarely described, consisting mainly into
      enthesopathy and non-synovial tendon degeneration. We present the case of a 50
      years old man with alkaptonuria and discuss the ultrasonographic findings and the
      relationship of the disease with chondrocalcinosis. The tendinous and synovial
      aspect may be peculiar and it could therefore allow recognition and screening for
      alkaptonuria, along with clinical and radiologic data. 

PMID- 24286098
TI  - Role and importance of Doppler ultrasound in the diagnosis of pulmonary
      sequestration: report of two adolescent cases.
AB  - Pulmonary sequestration is a rare pulmonary parenchymal anomaly. The localization
      of the aberrant artery and its relation with sequestration are of importance in
      the process of diagnosis in the preoperative period. The feeding artery can be
      identified by color Doppler ultrasonography. We report two cases of pulmonary
      sequestration in two adolescents, aged 11 and 13 years old, and this report
      documents the use of in which color Doppler ultrasound demonstrated the abnormal
      feeding artery. Color Doppler ultrasonography, a noninvasive and radiation-free
      imaging modality should be considered in the diagnostic algorithm of pulmonary
      sequestration. 

PMID- 24286099
TI  - Ultrasound diagnosis in two cases of severe craniofacial anomalies.
AB  - Holoprosencephaly (HPE) is a rare anomaly of the brain consisting of an absent or
      incomplete separation of the forebrain in early gestation. We present 2 variants
      of HPE, diagnosed by ultrasound, which combined with the clinical features led to
      HPE subtypes differentiation. 

PMID- 24286100
TI  - Advantages and pitfalls of elastosonography in the evaluation of cervical lymph
      nodes.

PMID- 24286101
TI  - Quiz answer. Young men with bilateral pain in the lower part of patella.

PMID- 24286102
TI  - UHPLC UHD Q-TOF MS/MS analysis of the impact of sulfur fumigation on the chemical
      profile of Codonopsis Radix (Dangshen).
AB  - Over recent decades sulfur fumigation has been becoming abused in processing some
      freshly harvested Chinese medicinal herbs, although it is questioned whether
      sulfur fumigation can result in changes in efficacy and safety of the herbs. One
      of the herbs commonly processed by sulfur fumigation is Codonopsis Radix
      (Dangshen). A report showed that lobetyolin content in sulfur-fumigated Dangshen
      was lower than in air-dried Dangshen. Whereas there is no investigation designed
      to compare the chemical profiles of the sulfur-fumigated Dangshen and the air
      dried Dangshen. In the present study, a rapid and versatile ultra-high
      performance liquid chromatography coupled with ultra-high resolution quadrupole
      time-of-flight mass spectrometry (UHPLC UHD Q-TOF MS/MS) method was developed for
      comprehensive analysis of the chemical profiles of sulfur-fumigated and air-dried
      Dangshen samples. Principal component analysis (PCA) and partial least squares
      discriminant analysis (PLS-DA) demonstrated that there were significant chemical
      differences between sulfur-fumigated and air-dried Dangshen samples. Among the
      changed components, 57 compounds were identified, in which 15 sulfur-containing
      compounds were detected only in sulfur-fumigated samples. The established methods
      were successfully applied to discriminate sulfur-fumigated Dangshen among
      commercial samples. Whether the chemical changes caused by sulfur fumigation
      affect the clinical efficacy and safety of Dangshen needs to be further
      investigated. 

PMID- 24286103
TI  - New insight into protein-nanomaterial interactions with UV-visible spectroscopy
      and chemometrics: human serum albumin and silver nanoparticles.
AB  - In recent years, great efforts have focused on the exploration and fabrication of
      protein nanoconjugates due to potential applications in many fields including
      bioanalytical science, biosensors, biocatalysis, biofuel cells and bio-based
      nanodevices. An important aspect of our understanding of protein nanoconjugates
      is to quantitatively understand how proteins interact with nanomaterials. In this
      report, human serum albumin (HSA) and citrate-coated silver nanoparticles (AgNPs)
      are selected as a case study of protein-nanomaterial interactions. UV-visible
      spectroscopy together with multivariate curve resolution by alternating least
      squares (MCR-ALS) algorithm is first exploited for the detailed study of AgNPs
      HSA interactions. Introduction of the chemometrics tool allows extracting the
      kinetic profiles, spectra and distribution diagrams of two major absorbing pure
      species (AgNPs and AgNPs-HSA conjugate). These resolved profiles are then
      analysed to give the thermodynamic, kinetic and structural information of HSA
      binding to AgNPs. Transmission electron microscopy, circular dichroism
      spectroscopy and Fourier transform infrared spectroscopy are used to further
      characterize the complex system. Moreover, a sensitive spectroscopic biosensor
      for HSA is fabricated with the MCR-ALS resolved concentration of absorbing pure
      species. It is found that the linear range for the HSA nanosensor was from 1.9 nM
      to 45.0 nM with a detection limit of 0.9 nM. It is believed that the proposed
      method will play an important role in the fabrication and optimization of a
      robust nanobiosensor or cross-reactive sensors array for the detection and
      identification of biocomponents. 

PMID- 24286104
TI  - High hydrostatic pressure: a probing tool and a necessary parameter in
      biophysical chemistry.
AB  - High pressures extending up to several thousands of atmospheres provide extreme
      conditions for biological organisms to survive. Recent studies are investigating
      the survival mechanisms and biological function of microorganisms under natural
      and laboratory conditions extending into the GigaPascal range, with applications
      to understanding the Earth's deep biosphere and food technology. High pressure
      has also emerged as a useful tool and physical parameter for probing changes in
      the structure and functional properties of biologically important macromolecules
      and polymers encountered in soft matter science. Here we highlight some areas of
      current interest in high pressure biophysics and physical chemistry that are
      emerging at the frontier of this cross-disciplinary field. 

PMID- 24286105
TI  - Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to
      alpha,beta,gamma,delta-unsaturated sulfonic esters: controlling regioselectivity
      by rational selection of electron-withdrawing groups.
AB  - Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to electron
      deficient dienes was developed through rational selection of electron-withdrawing
      groups on the dienes. Various chiral allylic phosphine derivatives were
      synthesized in good yields with high enantioselectivity (up to 96% ee). 

PMID- 24286106
TI  - A composite of Co nanoparticles highly dispersed on N-rich carbon substrates: an
      efficient electrocatalyst for Li-O(2) battery cathodes.
AB  - In this work, we present a facile sol-gel method to prepare a composite of Co
      nanoparticles highly dispersed on N-rich carbon substrates (Co-C composite). The
      assembled Li-O2 batteries with the composite as a cathode catalyst showed lower
      overpotential and better cyclability, and the improved performance may be
      attributed to the superior electrocatalytic activity of the Co-C composite. 

PMID- 24286107
TI  - Dispersible and discrete metalloporphyrin-based CMP nanoparticles enabling
      colorimetric detection and quantitation of gaseous SO2.
AB  - Metalloporphyrin-based CMP nanoparticles synthesized by the oxidative
      dimerization of terminal alkynes in the toluene-in-water miniemulsion possess
      native porosity, outstanding solution processability and uniform nanosized
      distribution. Also, they exhibit the sensitive color-switching ability for
      quantitative assay of gaseous SO2 by the noncovalent complex-displacement
      reaction at liquid-solid or gas-solid interfaces. 

PMID- 24286108
TI  - Broadband reflection of polymer-stabilized chiral nematic liquid crystals induced
      by a chiral azobenzene compound.
AB  - A chiral nematic liquid crystal-photopolymerizable monomer-chiral azobenzene
      compound composite was prepared and then polymerized under UV irradiation. The
      reflection wavelength of the composite can be extended to cover the 1000-2400 nm
      range and also be adjusted to the visible light region by controlling the
      concentration of chiral compounds. 

PMID- 24286109
TI  - [Excision of the head of the rib].

PMID- 24286110
TI  - [Excision of the ascending arch and descending aorta in intimal sarcoma
      originating in the aorta].

PMID- 24286111
TI  - [Imaging diagnosis Q & A. A fistula extending from the esophagus to the lower
      left lobe].

PMID- 24286112
TI  - Recyclable decoration of amine-functionalized magnetic nanoparticles with Ni(2+)
      for determination of histidine by photochemical vapor generation atomic
      spectrometry.
AB  - It is critically important to accurately determine histidine since it is an
      indicator for many diseases when at an abnormal level. Here, an inexpensive and
      simple method using an amine-functionalized magnetic nanoparticle-based Ni(2+)
      histidine affinity pair system was developed for highly sensitive and selective
      detection of histidine in human urine by photochemical vapor generation atomic
      spectrometry. Ni(2+) was first bound to the amine groups of the amine
      functionalized magnetic nanoparticles and then liberated to solution via the
      highly specific interaction between the histidine and Ni(2+) in the presence of
      histidine. The liberated histidine-Ni(2+) complex was exposed to UV irradiation
      in the presence of formic acid to form gaseous nickel tetracarbonyl, which was
      separated from the sample matrix and determined by atomic absorption/fluorescence
      spectrometry. Compared to other methods, this approach promises high sensitivity,
      simplicity in design, and convenient operation. The need for organic solvents,
      enzymatic reactions, separation processes, chemical modification, expensive
      instrumentations, and sophisticated and complicated pretreatment is minimized
      with this strategy. A limit of detection of 1 nM was obtained and provided tens
      to-hundreds of fold improvements over that achieved with conventional methods.
      The protocol was evaluated by analysis of several urine samples with good
      recoveries and showed great potential for practical application. 

PMID- 24286113
TI  - The joint impact of donor and recipient parameters on the outcome of heart
      transplantation in Germany after graft allocation.
AB  - Organ shortage in heart transplantation (HTx) results in increased use of grafts
      from donors with substantial risk factors. It is discussed controversially which
      donor characteristics may be detrimental. Therefore, we evaluated the joint
      impact of donor- and patient-related risk factors in HTx on patient survival by
      multiple analysis in a nationwide multicentre study after donor selection was
      carried out. The research database consists of data concerning hearts donated and
      transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung
      Organtransplantation and the BQS Institute. Multiple Cox regression (significance
      level 5%, hazard ratio [95% CI]) was conducted (n = 774, recipient age >= 18
      years). Survival was significantly decreased by donor age (1.021 [1.008-1.035]
      per year), nontraumatic cause of death (1.481 [1.079-2.034]), troponin >0.1 ng/ml
      (2.075 [1.473-2.921]), ischaemia time (1.197 [1.041-1.373] per hour), recipient
      age (1.017 [1.002-1.031] per year) and in recipients with pulmonary vascular
      resistance >= 320 dyn*s*cm(-5) (1.761 [1.115-2.781]), with ventilator dependency
      (3.174 [2.211-6.340]) or complex previous heart surgery (1.763 [1.270-2.449]).
      After donor selection had been conducted, multiple Cox regression revealed donor
      age, nontraumatic cause of death, troponin and ischaemia time as well as
      recipient age, pulmonary hypertension, ventilator dependency and previous complex
      heart surgery as limiting risk factors concerning patient survival.

PMID- 24286115
TI  - A pilot study to examine the tolerability and device preference in type 1
      diabetes of insulin aspart administered by InsuJet compared with subcutaneous
      injection.
AB  - BACKGROUND: Jet injectors allow needle-free insulin delivery. The study objective
      was to compare the tolerability and device preference of subcutaneous insulin
      aspart delivery by jet injector (InsuJetTM; European Pharma Group, Schiphol-Rijk,
      The Netherlands) with pen injection in an open-label, randomized, crossover pilot
      study. SUBJECTS AND METHODS: Ten participants with type 1 diabetes underwent two
      meal tolerance tests 1 week apart. Plasma glucose and serum insulin levels were
      sampled from 10 min preceding to 240 min after insulin aspart administration by
      InsuJet or FlexPen((r)) (Novo Nordisk Pharmaceuticals Pty. Ltd., Baulkham Hills,
      NSW, Australia). Insulin dose was calculated using participants' insulin-to
      carbohydrate ratios. Immediately after insulin administration, participants drank
      500 mL of Ensure((r)) (Abbott Australasia Pty. Ltd., Botany, NSW, Australia)
      (providing 2,240 kJ of energy, 18.6 g of protein, 96 g of carbohydrate, and 3 g
      of fat). RESULTS: In this small pilot study, the devices were similar in glucose
      excursion (median [quartile 1, quartile 3], InsuJet vs. FlexPen, 9.4 [4.8, 12.8]
      vs. 8.1 [5.4, 10.6] mmol/L; P=0.43), in the area under the glucose concentration
      time curve for 0-240 min corrected for baseline glucose level (InsuJet vs.
      FlexPen, 1,230 [623, 2,012] vs. 1,175 [91, 1,774] mmol . min/L; P=0.4), and in
      insulin absorption over the 240-min period. Devices were similar for participant
      preference and relative injection pain. CONCLUSIONS: Subcutaneous jet injection
      of aspart insulin was well tolerated.

PMID- 24286116
TI  - Comparative evaluation of the effects of treatment with tocilizumab and TNF-alpha
      inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid
      arthritis patients.
AB  - INTRODUCTION: Anemia of inflammation (AI) is a common complication of rheumatoid
      arthritis (RA) and has a negative impact on RA symptoms and quality of life.
      Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In
      this study, we evaluated and compared the effects of IL-6 and TNF-alpha blocking
      therapies on anemia, disease activity, and iron-related parameters including
      serum hepcidin in RA patients. METHODS: Patients (n = 93) were treated with an
      anti-IL-6 receptor antibody (tocilizumab) or TNF-alpha inhibitors for 16 weeks.
      Major disease activity indicators and iron-related parameters including serum
      hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation
      of treatment. Effects of tocilizumab and infliximab (anti-TNF-alpha antibody) on
      cytokine-induced hepcidin expression in hepatoma cells were analyzed by
      quantitative real-time PCR. RESULTS: Anemia at base line was present in 66% of
      patients. Baseline serum hepcidin-25 levels were correlated positively with serum
      ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF)
      levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia
      and disease activity, and reductions in serum hepcidin-25 levels were observed
      within 2 weeks in both groups, and these effects were more pronounced in the
      tocilizumab group than in the TNF-alpha inhibitors group. Serum hepcidin-25
      reduction by the TNF-alpha inhibitor therapy was accompanied by a decrease in
      serum IL-6, suggesting that the effect of TNF-alpha on the induction of hepcidin
      25 was indirect. In in vitro experiments, stimulation with the cytokine
      combination of IL-6+TNF-alpha induced weaker hepcidin expression than did with IL
      6 alone, and this induction was completely suppressed by tocilizumab but not by
      infliximab. CONCLUSIONS: Hepcidin-mediated iron metabolism may contribute to the
      pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective
      than TNF-alpha inhibitors for improving anemia and normalizing iron metabolism in
      RA patients by inhibiting hepcidin production.

PMID- 24286114
TI  - Long-term tolerability and maintenance of therapeutic response to sodium oxybate
      in an open-label extension study in patients with fibromyalgia.
AB  - INTRODUCTION: The long-term safety and therapeutic response of sodium oxybate
      (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period
      of up to 1 year in a prospective, multicenter, open-label, extension study in
      patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week
      trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo
      for treatment of FM. METHODS: This extension study comprised an additional 38
      weeks of treatment and was carried out at 130 clinical sites in 7 countries.
      Initial entry criteria for the previous 2 double-blind clinical trials required
      that patients aged >= 18 years met the American College of Rheumatology 1990
      criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score >= 50 on
      a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment
      in the extension study with SXB 4.5 g/night (administered in 2 equally divided
      doses) for at least 1 week, followed by possible serial 1.5 g/night dose
      increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum). RESULTS:
      Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed
      the study. The main reason for early discontinuation was adverse events (AEs;
      23.0% of patients). Patients were primarily middle-aged (mean 46.9 +/- 10.8
      years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9
      +/- 8.7 years. Serious AEs were experienced by 3.6% of patients. The most
      frequently reported AEs (incidence >= 5% at any dose or overall) were nausea,
      headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety,
      insomnia, influenza, somnolence, upper respiratory tract infection, muscle
      spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB
      therapeutic response was demonstrated with continued improvement from controlled
      study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores,
      and other measures. Responder analyses showed that 68.8% of patients achieved >=
      30% reduction in pain VAS and 69.7% achieved >= 30% reduction in FIQ total score
      at study endpoint. CONCLUSIONS: The long-term safety profile of SXB in FM
      patients was similar to that in the previously reported controlled clinical
      trials. Improvement in pain and other FM clinical domains was maintained during
      long-term use. TRIAL REGISTRATION: ClinicalTrials.gov NCT00423605.

PMID- 24286117
TI  - Drug prescriptions unadapted to the renal function in patients aged 80 years and
      older.
AB  - BACKGROUND: Drug-related problems are common in older people. Often they are
      related to low estimated glomerular filtration rate (eGFR), which has a high
      prevalence among older adults. OBJECTIVES: The aim of this study was to
      investigate inappropriate drug prescriptions and dose adaptations in a very old
      population and their relationship with the eGFR. METHODS:  DESIGN: A cross
      sectional study within a Belgian prospective population-based cohort study (the
      BELFRAIL study) of 539 participants aged 80 years and older (mean age 85 years).
      Drug prescriptions at inclusion were reported by the participant's responsible
      general practitioner. The eGFR was estimated using the MDRD equation. Based on
      their eGFR, the participants were divided in three groups: > 50, 30-50 and < 30
      ml/min/1.73 m2, respectively. Drug prescriptions were analysed in different eGFR
      groups. The prevalence and odds ratios of inappropriate drugs and the unadjusted
      defined daily doses (DDD) of the participant eGFRs were calculated. RESULTS:
      Thirty-six (of 111) and eight (of 31) of the participants with an eGFR between 30
      50 and < 30 ml/min/1.73 m2, respectively, had at least one inappropriate drug
      prescribed. No decrease in mean DDD, was observed in any prescribed drug in both
      lower eGFR groups. Participants with a lower eGFR were at higher risk of
      receiving gliclazide (OR: 4.51; 95% CI: 1.45-14.02) or unadjusted doses of
      allopurinol (OR: 3.48; 95% CI: 1.26-9.61). CONCLUSION: Drug prescriptions
      inappropriate for patient eGFR are common in subjects aged 80 years and older,
      despite automatic eGFR reporting.

PMID- 24286118
TI  - Are premature ventricular contractions always harmless?
AB  - INTRODUCTION: Premature ventricular contractions (PVCs) are among the most
      prevalent arrhythmias. PVCs lead to haemodynamically insufficient heartbeats.
      Their presence is considered rather insignificant, but this widespread assumption
      is not supported by research evidence. CASES: We present three cases of patients
      commonly seen in daily general practice, with a range of presentations, varying
      from incidental (harmless) PVCs to frequent and potentially symptomatic PVCs.
      DISCUSSION: In more frequent PVCs (> 10% heart beats) fatigue and exertional
      dyspnoea may occur. When > 20% of heart beats are PVCs, patients may develop
      cardiomyopathy and heart failure. Incidental PVCs are harmless. Anti-arrhythmic
      drug treatment should be considered in case of frequent PVCs but also catheter
      ablation appears an effective treatment option. CONCLUSION: Altogether, PVCs may
      not be harmless, depending on their occurrence rate. Research data from primary
      care settings on epidemiology and natural course is needed.

PMID- 24286119
TI  - MALDI-TOF MS, a useful instrument for differentiating metallo-beta-lactamases in
      Enterobacteriaceae and Pseudomonas spp.
AB  - We have evaluated a matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) method for the identification of carbapenemases
      and for distinguishing metallo-beta-lactamases (MBLs). A total of 49
      noncarbapenemase-producing and 14 carbapenemase-producing Enterobacteriaceae and
      Pseudomonas aeruginosa clinical strains, previously characterized by PCR, were
      included in the study. With MALDI-TOF MS, the presence of carbapenemases was
      confirmed by the detection of ertapenem hydrolysis (lost of molecular peaks:
      476.5 Da, 498.5 Da, 520.5 Da and presence of degradation products) in the mixture
      of the bacteria with the antibiotic, and classification was achieved by selective
      inhibition of carbapenemase activity (the ertapenem molecular peak was
      maintained) with ethylenediaminetetraacetic acid (EDTA). We obtained a good
      concordance among the results of PCR and MALDI-TOF MS. This method appears to be
      simple, fast and reliable for distinguishing in few hours different classes of
      carbapenemases, which can be very useful for epidemiological studies or to
      establish a specific antimicrobial therapy. SIGNIFICANCE AND IMPACT OF THE STUDY:
      MALDI-TOF mass spectrometry is increasingly present in microbiology laboratories
      due to its increasing use for bacterial identification. This study describes a
      method for detection of carbapenemase activity using MALDI-TOF, which is similar
      to the reference method: the detection of imipenem hydrolysis using UV
      spectrometry.

PMID- 24286121
TI  - Bodyweight in patients with idiopathic gastroparesis: roles of symptoms, caloric
      intake, physical activity, and body metabolism.
AB  - BACKGROUND: Most gastroparetic patients are underweight probably because of
      frequently experienced early satiety, nausea, and vomiting. Some gastroparesis
      (GP) patients, however, are overweight, for reasons that are not well understood.
      The aim of this study was to evaluate the factors that influence bodyweight such
      as resting energy and exercise-related expenditure, symptoms of early satiety,
      nausea and vomiting, and caloric intake in patients with idiopathic GP and in
      healthy controls. METHODS: Thirty-nine healthy controls and 29 subjects with
      idiopathic GP were studied. Resting energy expenditure (indirect calorimetry),
      body composition (bioelectrical impedance), dietary intake (Block Food Frequency
      Questionnaire), symptoms (Patient Assessment of Upper GI Symptoms), and physical
      activity (Paffenbarger exercise survey) were assessed. KEY RESULTS: Both median
      caloric intake (1242 vs 1804 kcal; p = 0.005) and caloric expenditure (486 vs
      2172 kcal; p < 0.01) were significantly lower in patients with GP as compared to
      controls although BMI (25.8 +/- 5.8 vs 24.3 +/- 4.0 kg/m2) and resting energy
      expenditure (1327 +/- 293 vs 1422 +/- 243 kcal) were similar. On the other hand,
      the 12 GP patients who had gained weight (GW) since diagnosis had lower symptom
      severity (12.9 +/- 4.4 vs 19.3 +/- 6.3; p < 0.05), consumed more calories (1342
      vs 1134 kcal; p = 0.08) and expended less calories for activity per week (406 vs
      644 median kcal; p = 0.45) compared to the 17 GP patients who had lost weight or
      remained weight neutral (LW). CONCLUSIONS & INFERENCES: Patients with GP,
      although in energy balance, consumed and expended less calories than healthy
      controls. A subgroup of patients with GP who were less symptomatic, gained weight
      because of increased caloric intake and reduced energy expenditure.

PMID- 24286120
TI  - GTP binding controls complex formation by the human ROCO protein MASL1.
AB  - The human ROCO proteins are a family of multi-domain proteins sharing a conserved
      ROC-COR supra-domain. The family has four members: leucine-rich repeat kinase 1
      (LRRK1), leucine-rich repeat kinase 2 (LRRK2), death-associated protein kinase 1
      (DAPK1) and malignant fibrous histiocytoma amplified sequences with leucine-rich
      tandem repeats 1 (MASL1). Previous studies of LRRK1/2 and DAPK1 have shown that
      the ROC (Ras of complex proteins) domain can bind and hydrolyse GTP, but the
      cellular consequences of this activity are still unclear. Here, the first
      biochemical characterization of MASL1 and the impact of GTP binding on MASL1
      complex formation are reported. The results demonstrate that MASL1, similar to
      other ROCO proteins, can bind guanosine nucleotides via its ROC domain.
      Furthermore, MASL1 exists in two distinct cellular complexes associated with heat
      shock protein 60, and the formation of a low molecular weight pool of MASL1 is
      modulated by GTP binding. Finally, loss of GTP enhances MASL1 toxicity in cells.
      Taken together, these data point to a central role for the ROC/GTPase domain of
      MASL1 in the regulation of its cellular function.

PMID- 24286122
TI  - Formae speciales of cereal powdery mildew: close or distant relatives?
AB  - Powdery mildew is an important disease of cereals, affecting both grain yield and
      end-use quality. The causal agent of powdery mildew on cereals, Blumeria
      graminis, has been classified into eight formae speciales (ff.spp.), infecting
      crops and wild grasses. Advances in research on host specificity and resistance,
      and on pathogen phylogeny and origins, have brought aspects of the subspecific
      classification system of B. graminis into ff.spp. into question, because it is
      based on adaptation to certain hosts rather than strict host specialization.
      Cereals therefore cannot be considered as typical non-hosts to non-adapted
      ff.spp. We introduce the term 'non-adapted resistance' of cereals to
      inappropriate ff.spp. of B. graminis, which involves both pathogen-associated
      molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI).
      There is no clear distinction between the mechanisms of resistance to adapted and
      non-adapted ff.spp. Molecular evolutionary data suggest that the taxonomic
      grouping of B. graminis into different ff.spp. is not consistent with the
      phylogeny of the fungus. Imprecise estimates of mutation rates and the lack of
      genetic variation in introduced populations may explain the uncertainty with
      regard to divergence times, in the Miocene or Holocene epochs, of ff.spp. of B.
      graminis which infect cereal crop species. We propose that most evidence favours
      divergence in the Holocene, during the course of early agriculture. We also
      propose that the forma specialis concept should be retained for B. graminis
      pathogenic on cultivated cereals to include clades of the fungus which are
      strongly specialized to these hosts, i.e. ff.spp. hordei, secalis and tritici, as
      well as avenae from cultivated A. sativa, and that the forma specialis concept
      should no longer be applied to B. graminis from most wild grasses. 

PMID- 24286123
TI  - Identification of a novel HLA-B allele, B*56:43, by sequence-based typing in a
      Lithuanian bone marrow donor.
AB  - A novel class I human leukocyte antigen allele HLA-B*56:43 is described. 

PMID- 24286125
TI  - Aortic wall destruction associated with a rare 11.5-cm ascending aortic aneurysm.

PMID- 24286124
TI  - Cytoprotection by endogenous zinc in the vertebrate retina.
AB  - Our recent studies have shown that endogenous zinc, co-released with glutamate
      from the synaptic terminals of vertebrate retinal photoreceptors, provides a
      feedback mechanism that reduces calcium entry and the concomitant vesicular
      release of glutamate. We hypothesized that zinc feedback may serve to protect the
      retina from glutamate excitotoxicity, and conducted in vivo experiments on the
      retina of the skate (Raja erinacea) to determine the effects of removing
      endogenous zinc by chelation. These studies showed that removal of zinc by
      injecting the zinc chelator histidine results in inner retinal damage similar to
      that induced by the glutamate receptor agonist kainic acid. In contrast, when an
      equimolar quantity of zinc followed the injection of histidine, the retinal cells
      were unaffected. Our results are a good indication that zinc, co-released with
      glutamate by photoreceptors, provides an auto-feedback system that plays an
      important cytoprotective role in the retina.

PMID- 24286126
TI  - The effect of vacuum-assisted closure in bacterial clearance of the infected
      abdomen.
AB  - BACKGROUND: Laparostomy with vacuum-assisted closure (VAC) plays an important
      role in improving survival in the presence of abdominal infection. We conducted a
      study of the qualitative changes in the bacterial flora of the peritoneal cavity
      in patients with severe abdominal infection treated with laparostomy and a VAC
      device. METHODS: Thirty-nine patients with severe abdominal infection treated
      with abdominal opening and VAC were registered in a clinical study. When an
      incidence of 53.8% of hospital-acquired peritoneal infection (HAPI) was found in
      the study patient population, it was decided to divide the patients in two groups
      according to whether or not they developed a HAPI. The patients' outcomes were
      then analyzed. RESULTS: The durations of abdominal opening (p=0.04), length of
      stay in the intensive care unit (ICU) (p=0.01), and of hospitalization (p=0.04)
      were significantly greater in patients with HAPI than in those without it,
      whereas mortality did not differ on the basis of these three variables.
      CONCLUSIONS: Superinfection is common in laparostomy done with a VAC device for
      managing severe abdominal infection. The data in the present study show that VAC
      does not alter the quality of the bacterial burden in primary abdominal
      contamination, nor does it seem to prevent a high incidence of HAPI. However, VAC
      is as effective in reducing mortality among patients with HAPI as among those
      without it.

PMID- 24286127
TI  - Looking beyond the post-genomic era.
AB  - A report on BioMed Central's fourth annual Beyond the Genome conference held at
      the University of California, San Francisco Mission Bay Conference Center, USA, 1
      3 October 2013.

PMID- 24286128
TI  - Survival of HIV-positive individuals with hepatitis B and C infection in
      Michigan.
AB  - We sought to estimate mortality and associated factors in HIV-hepatitis co
      infected individuals in Michigan using a retrospective cohort study. For the
      study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals
      were matched to hepatitis B and C cases. In the final Cox proportional hazards
      regression model, individuals of other [hazard ratio (HR) 2.2, 95% confidence
      interval (CI) 1.4-3.2] and black (HR 1.3, 95% CI 1.1-1.6) race had decreased
      survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2.1,
      95% CI 1.6-2.6), men who have sex with men (MSM)/IDUs (HR 1.5, 95% CI 1.1-2.2),
      individuals with undetermined risk (HR 1.5, 95% CI 1.2-1.9) and heterosexual
      practices (HR 1.4, 95% CI 1.1-1.8) had decreased survival compared to MSM.
      Additionally, an interaction was found between current HIV status and co
      infection. Mortality in HIV-hepatitis co-infected individuals remains a
      continuing problem. Our study can help in planning interventions to reduce
      mortality in HIV-infected individuals.

PMID- 24286129
TI  - Chromosomal organization and evolutionary history of Mariner transposable
      elements in Scarabaeinae coleopterans.
AB  - BACKGROUND: With the aim to increase the knowledge on the evolution of
      coleopteran genomes, we investigated through cytogenetics and nucleotide sequence
      analysis Mariner transposons in three Scarabaeinae species (Coprophanaeus
      cyanescens, C. ensifer and Diabroctis mimas). RESULTS: The cytogenetic mapping
      revealed an accumulation of Mariner transposon in the pericentromeric repetitive
      regions characterized as rich in heterochromatin and C0t-1 DNA fraction (DNA
      enriched with high and moderately repeated sequences). Nucleotide sequence
      analysis of Mariner revealed the presence of two major groups of Mariner copies
      in the three investigated coleoptera species. CONCLUSIONS: The Mariner is
      accumulated in the centromeric area of the coleopteran chromosomes probably as a
      consequence of the absence of recombination in the heterochromatic regions. Our
      analysis detected high diversification of Mariner sequences during the
      evolutionary history of the group. Furthermore, comparisons between the
      coleopterans sequences with other insects and mammals, suggest that the
      horizontal transfer (HT) could have acted in the spreading of the Mariner in
      diverse non-related animal groups.

PMID- 24286130
TI  - Is there a deafness duration limit for cochlear implants in post-lingual deaf
      adults?
AB  - CONCLUSION: Patients with post-lingual deafness should not be excluded from
      cochlear implantation (CI) on the basis of duration of deafness. We found that
      the prognosis was favorable in patients who developed deafness after adolescence,
      even in those with extremely long-term deafness. OBJECTIVES: CI is an effective
      treatment for post-lingual deafness. However, it remains unclear whether CI would
      benefit patients with extremely long-term deafness. We evaluated the auditory
      performance after CI of patients who had been deaf for more than 30 years.
      METHODS: The study enrolled 81 adults with post-lingual deafness. Speech
      perception tests were performed preoperatively and 12 months postoperatively, and
      factors affecting the postoperative auditory performance were investigated. The
      subjects were divided into groups according to the duration of deafness and the
      postoperative speech perception scores were compared. RESULTS: A marked
      improvement in the open-set speech perception scores (mono/disyllabic words and
      sentences) after implantation was seen in all groups, and no significant
      difference in the improvement in speech perception scores was observed among the
      groups. Age at onset of deafness was closely related to the postoperative
      performance, and patients who had lost their hearing before adolescence performed
      poorly.

PMID- 24286131
TI  - Ultrasound elastography is a reproducible and feasible tool for the evaluation of
      the patellar tendon in healthy subjects.
AB  - OBJECTIVE: To evaluate the feasibility and reproducibility of ultrasound
      elastography (UE) in the assessment of healthy patellar tendon and to describe
      its UE pattern. METHODS: Twenty-two patellar tendons of 11 out of 16 healthy
      subjects who met the inclusion criteria were evaluated three times by ultrasound
      (US) and UE at their proximal, middle and distal portions, by two separate
      sonographers with different experiences in UE. RESULTS: In all tendon portions
      the color map analysis showed a predominance of green (highly elastic), with good
      values of intra-observer (Operator 1: P-values = 0.790, 0.864, 0.865; Operator 2:
      P = 0.642, 0.882, 0.613 for proximal, middle and distal portions, respectively)
      and inter-observer (P = 0.657) agreement. For both operators the intra-observer
      analysis of the elasticity ratio (ER) between the tendon and the subcutis showed
      high agreement values (P < 0.001 for both operators). The inter-observer analysis
      showed also high agreement values (P < 0.001 at proximal, P = 0.001 at middle, P
      = 0.005 at distal portions). The overall analysis of the ER of the tendon
      portions showed values of (mean +/- SD): 1.47 +/- 0.64, 4.38 +/- 1.36, 3.32 +/-
      1.20 for proximal, middle and distal portions, respectively. The mean time to
      perform the UE evaluation for the inexperienced operator was 5 min at the
      beginning of the study but decreased to 2 min after a few examinations were done.
      The mean time for the expert was 2 min for the entire study. CONCLUSIONS: UE is a
      feasible and reproducible tool for the evaluation of the healthy patellar tendon
      and further data are needed to define its role in the assessment of tendon
      pathology.

PMID- 24286132
TI  - Low oxygen tension increased fibronectin fragment induced catabolic activities-
      response prevented with biomechanical signals.
AB  - INTRODUCTION: The inherent low oxygen tension in normal cartilage has
      implications on inflammatory conditions associated with osteoarthritis (OA).
      Biomechanical signals will additionally contribute to changes in tissue
      remodelling and influence the inflammatory response. In this study, we
      investigated the combined effects of oxygen tension and fibronectin fragment (FN
      f) on the inflammatory response of chondrocytes subjected to biomechanical
      signals. METHODS: Chondrocytes were cultured under free-swelling conditions at
      1%, 5% and 21% oxygen tension or subjected to dynamic compression in an ex vivo
      3D/bioreactor model with 29 kDa FN-f, interleukin-1beta (IL-1beta) and/or the
      nitric oxide synthase (NOS) inhibitor for 6 and 48 hours. Markers for catabolic
      activity (NO, PGE2), tissue remodelling (GAG, MMPs) and cytokines (IL-1beta, IL-6
      and TNFalpha) were quantified by biochemical assay. Aggrecan, collagen type II,
      iNOS and COX-2 gene expression were examined by real-time quantitative PCR. Two
      way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse data.
      RESULTS: Both FN-fs and IL-1beta increased NO, PGE2 and MMP production (all P<
      0.001). FN-f was more active than IL-1beta with greater levels of NO observed at
      5% than 1% or 21% oxygen tension (P < 0.001). Whilst FN-f reduced GAG synthesis
      at all oxygen tension, the effect of IL-1beta was significant at 1% oxygen
      tension. In unstrained constructs, treatment with FN-f or IL-1beta increased iNOS
      and COX-2 expression and reduced aggrecan and collagen type II (all P < 0.001).
      In unstrained constructs, FN-f was more effective than IL-1beta at 5% oxygen
      tension and increased production of NO, PGE2, MMP, IL-1beta, IL-6 and TNFalpha.
      At 5% and 21% oxygen tension, co-stimulation with compression and the NOS
      inhibitor abolished fragment or cytokine-induced catabolic activities and
      restored anabolic response. CONCLUSIONS: The present findings revealed that FN-fs
      are more potent than IL-1beta in exerting catabolic effects dependent on oxygen
      tension via iNOS and COX-2 upregulation. Stimulation with biomechanical signals
      abolished catabolic activities in an oxygen-independent manner and NOS inhibitors
      supported loading-induced recovery resulting in reparative activities. Future
      investigations will utilize the ex vivo model as a tool to identify key targets
      and therapeutics for OA treatments.

PMID- 24286133
TI  - A complex interaction between Wnt signaling and TNF-alpha in nucleus pulposus
      cells.
AB  - INTRODUCTION: Increased expression of the proinflammatory cytokine TNF-alpha in
      intervertebral discs (IVDs) leads to inflammation, which results in progressive
      IVD degeneration. We have previously reported that activation of Wnt-beta-catenin
      (hereafter called Wnt) signaling suppresses the proliferation of nucleus pulposus
      cells and induces cell senescence, suggesting that Wnt signaling triggers the
      process of degeneration of the IVD. However, it is not known whether cross talk
      between TNF-alpha and Wnt signaling plays a role in the regulation of nucleus
      pulposus cells. The goal of the present study was to examine the effect of the
      interaction between Wnt signaling and the proinflammatory cytokine TNF-alpha in
      nucleus pulposus cells. METHODS: Cells isolated from rat nucleus pulposus regions
      of IVDs were cultured in monolayers, and the expression and promoter activity of
      Wnt signaling and TNF-alpha were evaluated. We also examined whether the
      inhibition of Wnt signaling using cotransfection with Dickkopf (DKK) isoforms and
      Sclerostin (SOST) could block the effects of pathological TNF-alpha expression in
      nucleus pulposus cells. RESULTS: TNF-alpha stimulated the expression and promoter
      activity of Wnt signaling in nucleus pulposus cells. In addition, the activation
      of Wnt signaling by 6-bromoindirubin-3'-oxime (BIO), which is a selective
      inhibitor of glycogen synthase kinase 3 (GSK-3) activity that activates Wnt
      signaling, increased TNF-alpha expression and promoter activity. Conversely, the
      suppression of TNF-alpha promoter activity using a beta-catenin small interfering
      RNA was evident. Moreover, transfection with DKK-3, DKK-4, or SOST, which are
      inhibitors of Wnt signaling, blocked Wnt signaling-mediated TNF-alpha activation;
      these effects were not observed for DKK-1 or DKK-2. CONCLUSIONS: Here, we have
      demonstrated that Wnt signaling regulates TNF-alpha and that Wnt signaling and
      TNF-alpha form a positive-feedback loop in nucleus pulposus cells. The results of
      the present study provide in vitro evidence that activation of Wnt signaling
      upregulates the TNF-alpha expression and might cause the degeneration of nucleus
      pulposus cells. We speculate that blocking this pathway might protect nucleus
      pulposus cells against degeneration.

PMID- 24286134
TI  - Arterial hypertension assessed "out-of-office" in a contemporary cohort of
      rheumatoid arthritis patients free of cardiovascular disease is characterized by
      high prevalence, low awareness, poor control and increased vascular damage
      associated "white coat" phenomenon.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is associated with a high cardiovascular
      disease (CVD) risk, whereas arterial hypertension is a major modifiable CVD risk
      factor with still unclear prevalence in RA disease. We conducted a comprehensive
      study on hypertension characteristics evaluating for the first time out-of-office
      blood pressure (BP) in a typical contemporary RA cohort. METHODS: Assessment of
      office and out-of-office BP (when office systolic/diastolic BP was >129/79) and
      vascular studies including evaluation of aortic stiffness, carotid
      hypertrophy/plaques and ankle-brachial index, were performed in 214 consecutive,
      consenting RA patients free of CVD (aged 58.4 +/- 12.3 years, 82% women). As
      comparators regarding office hypertension measurements, data from 214 subjects
      (1:1 matched for age and gender with the RA patients) derived from a cohort
      designed to assess the prevalence of hypertension in the general population were
      used. RESULTS: The prevalence of declared known hypertension in the RA population
      was 44%. Of the remaining RA patients, 2 in every 5 individuals had abnormal
      office BP (systolic/diastolic >139/89 mmHg), contributing to almost double the
      prevalence of declared/office hypertension compared to the general matched
      population (67% vs. 34%). Out-of-office (home or ambulatory 24 hour) BP
      measurements revealed that: (i) a 54% prevalence of actual hypertension in RA, in
      other words almost 10% of the patients were unaware of having hypertension and
      (ii) 29% of the RA patients with known hypertension were not well controlled.
      Actual hypertension was positively associated with age and body mass index, and
      inversely with the use of biologic drugs. Overall, almost 1 out of 5 presented
      the 'white coat' phenomenon. An intermediately compromised vascular phenotype was
      evident in this "white coat" subgroup (lying between patients with sustained
      normotension and sustained hypertension) in terms of aortic stiffness, carotid
      hypertrophy and ankle-brachial index, even after adjustment for confounders.
      CONCLUSION: Beyond any doubt on the basis of out-of-office evaluation, arterial
      hypertension in RA has a high prevalence, low awareness and poor control, as well
      as substantial and vascular damage-associated "white coat" phenomenon. Thus,
      correct diagnosis and effective treatment of hypertension is of key importance in
      RA for CVD risk reduction.

PMID- 24286135
TI  - Multiple gene analyses of caligid copepods indicate that the reduction of a
      thoracic appendage in Pseudocaligus represents convergent evolution.
AB  - BACKGROUND: The Caligidae is a family of parasitic copepods containing over 30
      recognised genera. They are commercially important parasites as they cause
      disease in numerous finfish aquaculture facilities globally. Morphological
      features are used to distinguish between the genera and Pseudocaligus has
      traditionally been differentiated from Caligus solely by the presence of a much
      reduced form of the fourth thoracic leg. Currently there are numerous DNA
      sequences available for Caligus spp. but only the type species, Pseudocaligus
      brevipedis, has molecular data available, so systematic studies using molecular
      phylogenetic analyses have been limited. METHODS: Three gene regions, SSU rDNA,
      16S and CO1, for Pseudocaligus fugu from puffer fish from Japan and Pseudocaligus
      uniartus from rabbit fish from Indonesia are sequenced and molecular phylogenetic
      analyses performed in order to infer phylogenetic relationships between
      Pseudocaligus and other caligid copepods. RESULTS: The analysis revealed that
      there was no discrete grouping of Pseudocaligus spp. and that they had a
      polyphyletic distribution within Caligus taxa. Pseudocaligus fugu grouped with
      Caligus elongatus and contained a unique synapomorphy in the SSU rDNA region only
      seen in members of that clade. Pseudocaligus uniartus formed a well-supported
      group, in the SSU rDNA analyses, with a Caligus sp. that also infects rabbit
      fish, but was unresolved in the other analyses. Pseudocaligus brevipedis
      consistently and robustly grouped with Caligus curtus and C. centrodonti in all
      analyses. The majority of Lepeophtheirus spp. form a monophyletic sister group to
      the Caligus clade; however, L. natalensis is unresolved in all analyses and does
      not form part of the main Lepeophtheirus clade. CONCLUSIONS: These findings do
      not support the morphological-based distinction between Pseudocaligus and
      Caligus, suggesting that the reduced fourth leg is a feature that has evolved on
      multiple occasions throughout caligid evolution. Congruent molecular phylogenetic
      data support groupings based on the presence of morphological features, such as
      lunules, geography and host fish type rather than appendage morphology.
      Therefore, we support the synonymy of Pseudocaligus with Caligus.

PMID- 24286136
TI  - A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and
      early clinical response of brodalumab, a human anti-IL-17R antibody, in
      methotrexate-resistant rheumatoid arthritis.
AB  - INTRODUCTION: The aim of this study was to evaluate the safety, pharmacokinetics,
      and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL
      17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid
      arthritis (RA). METHODS: This phase Ib, randomized, placebo-controlled, double
      blind multiple ascending dose study enrolled subjects with moderate to severe RA
      (>= 6/66 swollen and >= 8/68 tender joints). Subjects were randomized 3:1 to
      receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6
      doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses
      per group) or placebo. Endpoints included incidence of adverse events (AEs) and
      pharmacokinetics. Exploratory endpoints included pharmacodynamics, and
      improvements in RA clinical metrics. RESULTS: Forty subjects were randomized to
      investigational product; one subject discontinued due to worsening of RA
      (placebo). The study was not designed to assess efficacy. AEs were reported by
      70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three
      serious AEs were reported in two subjects; there were no opportunistic
      infections. Brodalumab treatment resulted in inhibition of IL-17 receptor
      signaling and receptor occupancy on circulating leukocytes. No treatment effects
      were observed with individual measures of RA disease activity. On day 85 (week
      13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved
      ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved
      ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects
      achieved ACR70. CONCLUSIONS: Multiple dose administration of brodalumab was
      tolerated in subjects with active RA. There was no evidence of a clinical
      response to brodalumab in subjects with RA. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00771030.

PMID- 24286139
TI  - Fertilization capacity of cryopreserved Iberian ibex epididymal sperm in a
      heterologous in vitro fertilization assay.
AB  - In vitro fertilization (IVF) can be used to assess the fertilization capacity of
      sperm. Heterologous IVF may be useful when assessing that of wild animals as it
      is often difficult to obtain adequate numbers of naturally corresponding oocytes.
      The aim of the present study was to assess the fertilization capacity of frozen
      thawed ibex epididymal spermatozoa via heterologous IVF involving the oocytes of
      prepubertal domestic goats. The effect on fertilization and embryo development of
      adding oestrous sheep serum (ESS) to the fertilization medium was also examined.
      Cumulus-oocyte complexes (COCs) were matured in TCM-199 for 24-27 h at 38.5
      degrees C in a 5% CO2 in air atmosphere. Frozen-thawed epididymal spermatozoa
      were selected by density gradient centrifugation. After maturation, the oocytes
      were co-incubated with spermatozoa in synthetic oviductal fluid (SOF) with
      different concentrations of ESS: SOF-C (0%), SOF-2 (2%) and SOF-20 (20%). At 17 h
      post-insemination (hpi), zygotes with one female and one male pronucleus (2PN)
      were categorised as normal; zygotes with 3PN were recorded as polyspermic, and
      oocytes with 1PN as asynchronous. Cleavage and blastocyst development were
      assessed at 48 and 168 hpi respectively. The percentage of zygotes with 2PN was
      higher in the SOF-2 than in the SOF-20 treatment group (27.7% versus 2.9% P <
      0.05). The percentage of blastocysts formed with the SOF-C, SOF-2 and SOF-20
      treatments were 1.1%, 7.5% and 0% respectively. These results show that the
      presence of 2% ESS achieves better results than the use of no serum or the
      standard 20% concentration. Heterologous IVF may be an effective method for
      predicting the fertilization capacity of ibex spermatozoa, and therefore perhaps
      that of other wild mountain ungulates.

PMID- 24286138
TI  - The chromatin remodelling component SMARCB1/INI1 influences the metastatic
      behavior of colorectal cancer through a gene signature mapping to chromosome 22.
AB  - BACKGROUND: INI1 (Integrase interactor 1), also known as SMARCB1, is the most
      studied subunit of chromatin remodelling complexes. Its role in colorectal
      tumorigenesis is not known. METHODS: We examined SMARCB1/INI1 protein expression
      in 134 cases of colorectal cancer (CRC) and 60 matched normal mucosa by using
      tissue microarrays and western blot and categorized the results according to
      mismatch repair status (MMR), CpG island methylator phenotype, biomarkers of
      tumor differentiation CDX2, CK20, vimentin and p53. We validated results in two
      independent data sets and in cultured CRC cell lines. RESULTS: Herein, we show
      that negative SMARCB1/INI1 expression (11% of CRCs) associates with loss of CDX2,
      poor differentiation, liver metastasis and shorter patients' survival regardless
      of the MMR status or tumor stage. Unexpectedly, even CRCs displaying diffuse
      nuclear INI1 staining (33%) show an adverse prognosis and vimentin over
      expression, in comparison with the low expressing group (56%). The negative
      association of SMARCB1/INI1-lack of expression with a metastatic behavior is
      enhanced by the TP53 status. By interrogating global gene expression from two
      independent cohorts of 226 and 146 patients, we confirm the prognostic results
      and identify a gene signature characterized by SMARCB1/INI1 deregulation.
      Notably, the top genes of the signature (BCR, COMT, MIF) map on the long arm of
      chromosome 22 and are closely associated with SMARCB1/INI1. CONCLUSION: Our
      findings suggest that SMARCB1/INI1-dysregulation and genetic hot-spots on the
      long arm of chromosome 22 might play an important role in the CRC metastatic
      behavior and be clinically relevant as novel biomarkers.

PMID- 24286137
TI  - Role of neutrophils in systemic autoimmune diseases.
AB  - Neutrophils have emerged as important regulators of innate and adaptive immune
      responses. Recent evidence indicates that neutrophils display marked
      abnormalities in phenotype and function in various systemic autoimmune diseases,
      and may play a central role in initiation and perpetuation of aberrant immune
      responses and organ damage in these conditions. This review discusses the
      putative roles that neutrophils and aberrant neutrophil cell death play in the
      pathogenesis of various systemic autoimmune diseases, including systemic lupus
      erythematosus, small vessel vasculitis and rheumatoid arthritis. 

PMID- 24286141
TI  - CD97 and glioma invasion.

PMID- 24286140
TI  - Interferon alpha inhibits antigen-specific production of proinflammatory
      cytokines and enhances antigen-specific transforming growth factor beta
      production in antigen-induced arthritis.
AB  - INTRODUCTION: Interferon alpha (IFN-alpha) has a complex role in autoimmunity, in
      that it may both enhance and prevent inflammation. We have previously shown that
      the presence of IFN-alpha at sensitization protects against subsequent antigen
      triggered arthritis. To understand this tolerogenic mechanism, we performed a
      descriptive, hypothesis-generating study of cellular and humoral responses
      associated with IFN-alpha-mediated protection against arthritis. METHODS:
      Arthritis was evaluated at day 28 in mice given a subcutaneous injection of
      methylated bovine serum albumin (mBSA), together with Freund adjuvant and 0 to
      5,000 U IFN-alpha at days 1 and 7, followed by intraarticular injection of mBSA
      alone at day 21. The effect of IFN-alpha on mBSA-specific IgG1, IgG2a, IgG2b,
      IgA, and IgE was evaluated by enzyme-linked immunosorbent assay (ELISA).
      Cytokines in circulation and in ex vivo cultures on mBSA restimulation was
      evaluated with ELISA and Luminex, and the identity of cytokine-producing cells by
      fluorescence-activated cell sorting (FACS) analysis. RESULTS: Administration of
      IFN-alpha protected mice from arthritis in a dose-dependent manner but had no
      effect on antigen-specific antibody levels. However, IFN-alpha did inhibit the
      initial increase of IL-6, IL-10, IL-12, and TNF, and the recall response induced
      by intraarticular mBSA challenge of IL-1beta, IL-10, IL-12, TNF, IFN-gamma, and
      IL-17 in serum. IFN-alpha decreased both macrophage and CD4+ T cell-derived IFN
      gamma production, whereas IL-17 was decreased only in CD4+ T cells. Ex vivo, in
      mBSA-restimulated spleen and lymph node cell cultures, the inhibitory effect of
      in vivo administration of IFN-alpha on proinflammatory cytokine production was
      clearly apparent, but had a time limit. An earlier macrophage-derived, and
      stronger activation of the antiinflammatory cytokine transforming growth factor
      beta (TGF-beta) was observed in IFN-alpha-treated animals, combined with an
      increase in CD4+ T cells producing TGF-beta when arthritis was triggered by mBSA
      (day 21). Presence of IFN-alpha at immunizations also prevented the reduction in
      TGF-beta production, which was induced by the intraarticular mBSA injection
      triggering arthritis in control animals. CONCLUSIONS: Administration of IFN-alpha
      has a profound effect on the cellular response to mBSA plus adjuvant, but does
      not affect antigen-specific Ig production. By including IFN-alpha at
      immunizations, spleen and lymph node cells inhibit their repertoire of antigen
      induced proinflammatory cytokines while enhancing antiinflammatory TGF-beta
      production, first in macrophages, and later also in CD4+ T cells. On
      intraarticular antigen challenge, this antiinflammatory state is reenforced,
      manifested as inhibition of proinflammatory recall responses and preservation of
      TGF-beta levels. This may explain why IFN-alpha protects against antigen-induced
      arthritis.

PMID- 24286142
TI  - The role for adjuvant radiotherapy in the treatment of hemangiopericytoma: a
      Surveillance, Epidemiology, and End Results analysis.
AB  - OBJECT: Central nervous system (CNS) hemangiopericytomas are relatively uncommon
      and unique among CNS tumors as they can originate from or develop metastases
      outside of the CNS. Significant difference of opinion exists in the management of
      these lesions, as current treatment paradigms are based on limited clinical
      experience and single-institution series. Given these limitations and the absence
      of prospective clinical trials within the literature, nationwide registries have
      the potential to provide unique insight into the efficacy of various therapies.
      METHODS: The authors queried the Surveillance Epidemiology and End Results (SEER)
      database to investigate the clinical behavior and prognostic factors for
      hemangiopericytomas originating within the CNS during the years 2000-2009. The
      SEER survival data were adjusted for demographic factors including age, sex, and
      race. Univariate and multivariate analyses were performed to identify
      characteristics associated with overall survival. RESULTS: The authors identified
      227 patients with a diagnosis of CNS hemangiopericytoma. The median length of
      follow-up was 34 months (interquartile range 11-63 months). Median survival was
      not reached, but the 5-year survival rate was 83%. Univariate analysis showed
      that age and radiation therapy were significantly associated with survival.
      Moreover, young age and supratentorial location were significantly associated
      with survival on multivariate analysis. Most importantly, multivariate analysis
      using the Cox proportional hazards model showed a statistically significant
      survival benefit for patients treated with gross-total resection (GTR) in
      combination with adjuvant radiation treatment (HR 0.31 [95% CI 0.01-0.95], p =
      0.04), an effect not appreciated with GTR alone. CONCLUSIONS: The authors
      describe the epidemiology of CNS hemangiopericytomas in a large, national cancer
      database, evaluating the effectiveness of various treatment paradigms used in
      clinical practice. In this study, an overall survival benefit was found when GTR
      was accomplished and combined with radiation therapy. This finding has not been
      appreciated in previous series of patients with CNS hemangiopericytoma and
      warrants future investigations into the role of upfront adjuvant radiation
      therapy.

PMID- 24286143
TI  - Crossover and clinical outcomes in the Barrow Ruptured Aneurysm Trial.

PMID- 24286144
TI  - Delayed leptomeningeal and subependymal seeding after multiple surgeries for
      supratentorial diffuse low-grade gliomas in adults.
AB  - OBJECT: Diffuse WHO Grade II glioma (diffuse low-grade glioma [DLGG]) is an
      infiltrative brain tumor that usually migrates along the white matter fibers. The
      delayed CSF dissemination of supratentorial DLGGs is an exceptional complication
      and is rarely described in adults. Here, the authors report outcomes in a
      surgical series of 9 patients with DLGGs with subsequent leptomeningeal and/or
      subependymal seeding (LMSS) following multiple incomplete resections. METHODS:
      The authors performed a retrospective review of patients who underwent surgery
      for histopathologically confirmed WHO Grade II gliomas between 1998 and 2012 and
      experienced a secondary CSF spread. Information regarding clinical features,
      surgical procedures, histopathological results, adjuvant treatment, and clinical
      outcomes was collected and analyzed. RESULTS: Nine consecutive patients were
      included in this study. There were 6 men and 3 women whose mean age was 35.5
      years (range 22-59 years) at the time of initial symptom onset. All patients
      underwent surgery with the aid of intraoperative mapping, with incomplete tumor
      removal because of invasion of eloquent structures. The neuropathological
      examination diagnosed a DLGG in all cases (7 oligodendrogliomas, 1 astrocytoma,
      and 1 oligoastrocytoma). Five patients had a 1p19q codeletion. Because of tumor
      regrowth, the 9 patients underwent reoperation (2 surgeries in 6 cases and 3
      surgeries in 3 cases), again with incomplete resection. There were no surgical
      complications. Adjuvant therapy (radiotherapy and chemotherapy) was administered
      in all patients because of progression to a higher grade of malignancy that was
      histopathologically confirmed in all tumors. The patients suddenly worsened, and
      the diagnosis of LMSS was made with a mean delay of 77 months (range 27-140
      months) after the initial symptom onset. Six patients benefited from salvage
      chemotherapy while palliative care was chosen in 3 cases. The median survival in
      the 6 patients who underwent LMSS treatment was significantly longer than that in
      the 3 patients who did not receive salvage chemotherapy (p = 0.03). Indeed, all
      patients died, with a mean delay between the diagnosis of LMSS and death of 11
      months (range 2-38 months) and with a mean delay between the initial symptom
      onset and death of 88 months (range 34-144 months). CONCLUSIONS: Cerebrospinal
      fluid dissemination of DLGG is a rare but possible event. It can occur throughout
      the progression of WHO Grade II oligodendrogliomas, oligoastrocytomas, and
      astrocytomas, regardless of 1p19q status. This complication seems to appear in
      patients who have undergone multiple incomplete resections. Salvage therapy can
      be considered in patients with good neurological status. However, LMSS is
      associated with a decreased overall survival. Therefore, this rare entity
      deserves further multicenter studies to better understand its pathophysiology and
      to adapt therapeutic strategies.

PMID- 24286145
TI  - Generation of a patient-derived chordoma xenograft and characterization of the
      phosphoproteome in a recurrent chordoma.
AB  - OBJECT: The management of patients with locally recurrent or metastatic chordoma
      is a challenge. Preclinical disease models would greatly accelerate the
      development of novel therapeutic options for chordoma. The authors sought to
      establish and characterize a primary xenograft model for chordoma that faithfully
      recapitulates the molecular features of human chordoma. METHODS: Chordoma tissue
      from a recurrent clival tumor was obtained at the time of surgery and implanted
      subcutaneously into NOD-SCID interleukin-2 receptor gamma (IL-2Rgamma) null (NSG)
      mouse hosts. Successful xenografts were established and passaged in the NSG mice.
      The recurrent chordoma and the derived human chordoma xenograft were compared by
      histology, immunohistochemistry, and phospho-specific immunohistochemistry. Based
      on these results, mice harboring subcutaneous chordoma xenografts were treated
      with the mTOR inhibitor MLN0128, and tumors were subjected to phosphoproteome
      profiling using Luminex technology and immunohistochemistry. RESULTS: SF8894 is a
      novel chordoma xenograft established from a recurrent clival chordoma that
      faithfully recapitulates the histopathological, immunohistological, and
      phosphoproteomic features of the human tumor. The PI3K/Akt/mTOR pathway was
      activated, as evidenced by diffuse immunopositivity for phospho-epitopes, in the
      recurrent chordoma and in the established xenograft. Treatment of mice harboring
      chordoma xenografts with MLN0128 resulted in decreased activity of the
      PI3K/Akt/mTOR signaling pathway as indicated by decreased phospho-mTOR levels (p
      = 0.019, n = 3 tumors per group). CONCLUSIONS: The authors report the
      establishment of SF8894, a recurrent clival chordoma xenograft that mimics many
      of the features of the original tumor and that should be a useful preclinical
      model for recurrent chordoma.

PMID- 24286147
TI  - Bypass surgery for complex middle cerebral artery aneurysms: impact of the exact
      location in the MCA tree.
AB  - OBJECT: The object of this study was to describe the authors' institutional
      experience in the treatment of complex middle cerebral artery (MCA) aneurysms
      necessitating bypass and vessel sacrifice. METHODS: Cases in which patients with
      MCA aneurysms were treated with a combination of bypass and parent artery
      sacrifice were reviewed retrospectively. RESULTS: The authors identified 24
      patients (mean age 46 years) who were treated with bypass and parent artery
      sacrifice. The aneurysms were located in the M1 segment in 7 patients, MCA
      bifurcation in 8, and more distally in 9. The mean aneurysm diameter was 30 mm
      (range 7-60 mm, median 26 mm). There were 8 saccular and 16 fusiform aneurysms.
      Twenty-one extracranial-intracranial and 4 intracranial-intracranial bypasses
      were performed. Partial or total trapping (only) of the parent artery was
      performed in 17 cases, trapping with resection of aneurysm in 3, and aneurysm
      clipping with sacrifice of an M2 branch in 4. The mean follow-up period was 27
      months. The aneurysm obliteration rate was 100%. No recanalization of the
      aneurysms was detected during follow-up. There was 1 perioperative death (4%
      mortality rate) and 6 cerebrovascular accidents, causing permanent morbidity in 5
      patients. The median modified Rankin Scale score of patients with an M1 aneurysm
      increased from 0 preoperatively to 2 at latest follow-up, while the score was
      unchanged in other patients. Most of the permanent deficits were associated with
      M1 aneurysms. Twenty-one patients (88%) had good outcome as defined by a Glasgow
      Outcome Scale score of 4 or 5. CONCLUSIONS: Bypass in combination with parent
      vessel occlusion is a useful technique with acceptable frequencies of morbidity
      and mortality for complex MCA aneurysms when conventional surgical or
      endovascular techniques are not feasible. The location of the aneurysm should be
      considered when planning the type of bypass and the site of vessel occlusion.
      Flow alteration by partial trapping may be preferable to total trapping for the
      M1 aneurysms.

PMID- 24286148
TI  - Impact of preoperative anemia on outcomes in patients undergoing elective cranial
      surgery.
AB  - OBJECT: The objective of this study was to assess whether preoperative anemia in
      patients undergoing elective cranial surgery influences outcomes in the immediate
      perioperative period (<= 30 days). METHODS: The National Surgical Quality
      Improvement Program (NSQIP) was used to identify 6576 patients undergoing
      elective cranial surgery between 2006 and 2011. Propensity scores were used to
      match patients with moderate to severe anemia (moderate-severe) or mild anemia
      with patients without anemia. Logistic regression analysis was used to predict
      the outcomes of interest. Sensitivity analyses were used to limit the sample to
      patients without perioperative transfusion as well as those who underwent
      craniotomy for definitive resection of a malignant brain tumor. RESULTS: A total
      of 6576 patients underwent elective cranial surgery, of whom 175 had moderate
      severe anemia and 1868 had mild anemia. Patients with moderate-severe (odds ratio
      1.8, 95% CI 1.1-2.8) and mild (odds ratio 1.5, 95% CI 1.3-1.7) anemia were more
      likely to have prolonged length of stay (LOS) in the hospital compared to those
      with no anemia. Similarly, in patients who underwent craniotomy for a malignant
      tumor resection (n = 2537), anemia of any severity was associated with prolonged
      LOS, but not postoperative complications nor death. CONCLUSIONS: Anemia is not
      associated with an overall increased risk for adverse outcomes in patients
      undergoing elective cranial surgery. However, patients with anemia are more
      likely to experience prolonged hospitalization postoperatively, resulting in
      increased resource utilization.

PMID- 24286149
TI  - Haptoglobin genotype.

PMID- 24286150
TI  - SEER insights.

PMID- 24286151
TI  - SEER analysis and statistical judgment.

PMID- 24286152
TI  - Value-based neurosurgery: the example of microvascular decompression surgery.
AB  - OBJECT: Value of care is emerging as a promising framework to restructure health
      care, emphasizing the importance of reporting multiple outcomes that encompass
      the entire care episode instead of isolated outcomes specific to care points
      during a patient's care. The authors assessed the impact of coordinated
      implementation of processes across the episode of surgical care on value of
      neurosurgical care, using microvascular decompression (MVD) as an example.
      METHODS: This study is a retrospective review of consecutive cases involving
      patients with either trigeminal neuralgia or hemifacial spasm undergoing first
      time MVD. Patients were divided into 2 groups: Group 1 included patients who
      underwent surgery between February 2008 and November 2009 and Group 2 included
      those who underwent surgery between January 2011 and October 2012. The authors
      collected data on outcome measures spanning the entire surgical episode of care
      according to the Outcome Measures Hierarchy. RESULTS: Forty-nine patients were
      included: 20 patients in Group 1 and 29 patients in Group 2. Thirty-one patients
      underwent MVD for trigeminal neuralgia and 18 for hemifacial spasm. A zero
      mortality rate and high degree of symptom resolution were achieved in both
      groups. Group 2 benefited from a reduction in the average total operating room
      time, a decrease in the mean and median postoperative length of hospital stay, a
      decrease in the mean length of stay on the floor, and a reduction in the rates of
      complications and readmissions. CONCLUSIONS: Comprehensive implementation of
      improvement processes throughout the continuum of care resulted in improved
      global outcome and greater value of delivered care. Enhanced-recovery
      perioperative protocols and diagnosis-specific clinical pathways are two avenues
      built around global care delivery that can help achieve an "optimal episode of
      surgical care" in every case.

PMID- 24286154
TI  - Levetiracetam versus (fos)phenytoin for seizure prophylaxis in pediatric patients
      with intracranial hemorrhage.
AB  - OBJECT: Seizure prophylaxis is used in a variety of conditions, including
      supratentorial intracranial hemorrhage (ICH). In adults, studies have
      demonstrated phenytoin as the drug of choice for seizure prophylaxis; in
      children, levetiracetam is often provided due to its favorable side effect
      profile and pharmacokinetics. This study evaluated the difference in efficacy
      between these treatment options. METHODS: This retrospective review included 126
      patients between 1 month and 17 years of age with acute supratentorial ICH; all
      received seizure prophylaxis. Demographic data and outcome assessments were
      compared. RESULTS: Seizure prophylaxis was provided with (fos)phenytoin in 40
      children, levetiracetam in 61 children, and both drugs in 25 patients. Baseline
      characteristics of the treatment groups were similar, except that more patients
      treated with (fos)phenytoin had seizures on presentation. Patients treated solely
      with (fos)phenytoin had a higher probability of early seizures (within 7 days of
      ICH) compared with those treated only with LVT, controlling for relevant
      variables including seizures on presentation (OR 24.6, p = 0.002). Patients
      treated with (fos)phenytoin were more likely to need additional antiepileptic
      drugs for seizure control (p = 0.005). There was no significant difference in the
      incidence of late seizures (> 7 days after ICH) (p = 0.265). Adverse events
      necessitating a change in therapy were uncommon. CONCLUSIONS: Levetiracetam is a
      reasonable alternative to (fos)phenytoin for prophylaxis of early posthemorrhagic
      seizures. Levetiracetam and (fos)phenytoin are well tolerated in children.
      Prospective studies are needed to determine superiority, optimal dosing, and
      impact on long-term outcomes.

PMID- 24286155
TI  - Hemodynamically significant venous collapse underlying neonatal hydrocephalus.
AB  - OBJECT: It is known that CSF diversion in neonatal hydrocephalus can
      significantly increase cerebral blood flow, suggesting that a rapidly reversible
      elevation in vascular resistance underlies this disorder. Various sites of
      vascular compression have been described in the literature, from the arterioles
      to the capillary bed to the venules and sinuses. The purpose of this study was to
      define the site of the hemodynamically significant vascular compression seen in
      neonatal hydrocephalus. METHODS: The author performed a retrospective review of
      all patients who, in the first 28 days of life, had undergone 3-T MRI
      examination, including MR venography and susceptibility weighted scanning, at a
      tertiary care referral hospital in the period from April 2010 to April 2013. The
      maximum size of the subependymal veins over the thalamus and transverse sinuses
      was measured. RESULTS: Three children with hydrocephalus were identified, and 10
      children with a normal ventricular size served as controls. The subependymal
      veins were twice as prominent and the transverse sinuses were half as large in
      the patients with hydrocephalus compared with those in controls. CONCLUSIONS: The
      hemodynamically significant elevation in vascular resistance, which occurs in
      neonatal hydrocephalus, appears to be located in the venous sinuses.

PMID- 24286153
TI  - Haptoglobin genotype and functional outcome after aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECT: Haptoglobin allele heterogeneity has been implicated in differential
      reactive oxidant inhibition and inflammation. Haptoglobin alpha2-alpha2 has a
      lower affinity for binding hemoglobin, and when bound to hemoglobin, is cleared
      less easily by the body. The authors hypothesized that haptoglobin alpha2-alpha2
      genotype should be less protective for downstream injury after aneurysmal
      subarachnoid hemorrhage (aSAH) and should portend a worse outcome. METHODS:
      Patients with Fisher Grade 2 or higher aSAH were enrolled in the study.
      Genotyping for haptoglobin genotype was performed from blood and/or CSF.
      Demographic information, medical condition variables, and hospital course were
      abstracted from the medical record upon enrollment into the study. Outcome data
      (modified Rankin Scale score, Glasgow Outcome Scale score, and mortality) were
      collected at 3 months posthemorrhage. RESULTS: The authors enrolled 193 patients
      who ranged in age from 18 to 75 years. Only Caucasians were used in this analysis
      to minimize bias from variable haptoglobin allele frequencies in populations of
      different ancestral backgrounds. The sample had more women than men (overall mean
      age 54.45 years). Haptoglobin alpha2 homozygotes were older than the other
      individuals in the study sample (57.27 vs 53.2 years, respectively; p = 0.02) and
      were more likely to have Fisher Grade 3 SAH (p = 0.02). Haptoglobin alpha2-alpha2
      genotype, along with Fisher grade and Hunt and Hess grade, was associated with a
      worse 3-month outcome compared to those with the haptoglobin alpha1-alpha1
      genotype according to modified Rankin Scale score after controlling for
      covariates (OR 4.138, p = 0.0463). CONCLUSIONS: Patients with aSAH who carry the
      haptoglobin alpha2-alpha2 genotype had a worse outcome. Interestingly, the
      presence of a single alpha-2 allele was associated with worse outcome, suggesting
      that the haptoglobin alpha-2 protein may play a role in the pathology of brain
      injury following aSAH, although the mechanism for this finding requires further
      research. The haptoglobin genotype may provide additional information on
      individual risk of secondary injury and recovery to guide care focused on
      improving outcomes.

PMID- 24286156
TI  - Intraoperative cerebral angiography in arteriovenous malformation resection in
      children: a single institutional experience.
AB  - OBJECT: The use of cerebral intraoperative angiography has been described in
      resection of arteriovenous malformations (AVMs) in adults. More recently, studies
      have described experiences with intraoperative angiography in a small number of
      children. However, data on the safety and clinical utility of intraoperative
      angiography in the pediatric population remains limited in comparison with
      available data in adults. The aim of the study was to evaluate the use of
      cerebral intraoperative angiography in children undergoing AVM resection. The
      clinical utility of intraoperative angiography and procedure-related
      complications were evaluated. METHODS: A retrospective review was performed for
      all patients undergoing cerebral AVM resection with intraoperative angiography at
      The Children's Hospital of Philadelphia between 2008 and 2012. Patient imaging
      and operative and medical notes were reviewed to evaluate for end points of the
      study. A total of 17 patients (8 males, 9 females) were identified, with a median
      age of 12.1 years (range 1.2-17.9 years) and median weight of 45.5 kg (range 12.1
      78.9 kg). RESULTS: A total of 21 intraoperative angiography procedures were
      performed for 18 AVM resections in 17 patients. The technical success rate was
      94%. In 2 cases (11%), intraoperative angiography demonstrated a residual AVM,
      and repeat resections were performed. In both cases, no recurrent disease was
      noted on postoperative follow-up. One procedure-related complication (4.8%)
      occurred in 1 patient who was positioned prone. Recurrence to date was noted in 2
      (14%) of the 14 cases with available postoperative follow-up at 3.5 and 4.7
      months following resection with intraoperative angiography. The median follow-up
      time from intraoperative angiography to the most recent postoperative angiography
      was 1.1 years (range 4.3 months to 3.8 years). CONCLUSIONS: Intraoperative
      angiography is an effective and safe adjunct for surgical management of cerebral
      AVMs in the pediatric population.

PMID- 24286157
TI  - Reduction cranioplasty with the aid of simulated computer imaging for the
      treatment of hydrocephalic macrocephaly.
AB  - OBJECT: The occurrence of hydrocephalic macrocephaly is uncommon. When the
      condition does occur, it is usually seen in infants and young children. Patients
      with this disorder have an excessively enlarged head and weak physical
      conditions. Various surgical techniques of reduction cranioplasty for the
      treatment of these patients have been reported. In this study, a revised surgical
      procedure with the aid of simulated computer imaging for the treatment of
      hydrocephalic macrocephaly is presented. METHODS: Five cases of hydrocephalic
      macrocephaly in children ranging in age from 16 to 97 months were reviewed. These
      patients underwent surgical treatment at The First Affiliated Hospital of Xiamen
      University over a period of 4 years from January 2007 to January 2011. After
      physical examination, a 3D computer imaging system to simulate the patient's
      postoperative head appearance and bone reconstruction was established. Afterward,
      for each case an appropriate surgical plan was designed to select the best
      remodeling method and cranial shape. Then, prior to performing reduction
      remodeling surgery in the patient according to the computer-simulated procedures,
      the surgeon practiced the bone reconstruction technique on a plaster head model
      made in proportion to the patient's head. In addition, a sagittal bandeau was
      used to achieve stability and bilateral symmetry of the remodeled cranial vault.
      Each patient underwent follow-up for 6-32 months. RESULTS: Medium-pressure
      ventriculoperitoneal shunt surgery or shunt revision procedures were performed in
      each patient for treating hydrocephalus, and all patients underwent total cranial
      vault remodeling to reduce the cranial cavity space. Three of the 5 patients
      underwent a single-stage surgery, while the other 2 patients underwent total
      cranial vault remodeling in the first stage and the ventriculoperitoneal shunt
      operation 2 weeks later because of unrecovered hydrocephalus. All patients had
      good outcome with regard to hydrocephalus and macrocephaly. CONCLUSIONS: There
      are still no standard surgical strategies for the treatment of hydrocephalic
      macrocephaly. Based on their experience, the authors suggest using a computer
      imaging system to simulate a patient's postoperative head appearance and bone
      reconstruction together with total cranial vault remodeling with shunt surgery in
      a single-stage or 2-stage procedure for the successful treatment of hydrocephalic
      macrocephaly.

PMID- 24286158
TI  - Return to system within 30 days of pediatric neurosurgery.
AB  - OBJECT: Quality assessment measures have not been well developed for pediatric
      neurosurgical patients. This report documents the authors' experience in
      extracting information from an administrative database to establish the rate of
      return to system within 30 days of pediatric neurosurgical procedures. METHODS:
      Demographic, socioeconomic, and clinical characteristics were prospectively
      collected in administrative, business, and operating room databases. The primary
      end point was an unexpected return to the hospital system within 30 days from the
      date of a pediatric neurosurgical procedure. Statistical methods were used to
      identify clinical and demographic factors associated with the primary end point.
      RESULTS: There were 1358 pediatric neurosurgical procedures performed in the
      Children's Healthcare of Atlanta operating rooms in 2012, with 37.4% of these
      surgeries being preceded by admissions through the emergency department. Medicare
      or Medicaid was the payor for 54.9% of surgeries, and 37.6% of surgeries were
      shunt related. There were 148 unexpected returns to the system within 30 days
      after surgery, and in 109 of these cases, the patient had a presenting complaint
      that was attributable to the index surgery (related returns). The most common
      complaints were headache, nausea, vomiting, or seizure after shunt revision or
      cranial procedures (n = 62). The next most common reason for re-presentation was
      for wound concerns (n = 30). Thirty-seven of the 109 related returns resulted in
      a reoperation. The monthly rate of related returns was 8.1% +/- 2.5% over the 12
      month study period. When using related returns as the dependent variable, the
      authors found that patients who underwent a shunt-related surgery were both more
      likely to unexpectedly return to the system (OR 1.86, p = 0.008) and to require
      surgery upon readmission (OR 3.28, p = 0.004). Because an extended
      hospitalization shortened the window of time for readmission after surgery,
      extended length of stay was protective against return to system within 30 days of
      surgery. Importantly, if related and unrelated returns were analyzed together as
      the dependent variable (n = 148), no independent clinical and demographic risk
      factor could be identified. CONCLUSIONS: Quality assessment measures need to be
      clearly and carefully defined, as the definition itself will impact the
      analytical results. Clinicians must play a leading role in the development of
      these measures to ensure their clinical meaningfulness.

PMID- 24286159
TI  - Predicting type 2 diabetes mellitus using haemoglobin A1c: a community-based
      historic cohort study.
AB  - BACKGROUND: The ADA 2010 guidelines added HbA1c >= 6.5% as a criterion for
      diagnosing diabetes mellitus type 2. OBJECTIVE: To evaluate the HbA1c test in
      predicting type 2 diabetes in a high risk population. METHODS: A community-based
      historic cohort study was conducted including 10 201 patients, who had not been
      diagnosed with diabetes, and who underwent HbA1c test during the years 2002-2005.
      Data was retrieved on diabetes risk factors and the onset of diabetes (according
      to the ADA 2003 criteria), during a follow-up period of five-to-eight years.
      RESULTS: Mean age was 58.25 +/- 15.58 years; mean HbA1c level was 5.59 +/- 0.55%
      and 76.8% had a BMI > 25 kg/m(2) (mean: 30.74 +/- 8.30). In a Cox proportional
      hazards regression model, the risk of developing type 2 diabetes was 2.49 (95%
      CI: 1.29-3.71) for 5.5% <= HbA1c < 6% at baseline, 4.82 (95% CI: 2.83-8.20) for
      6% <= HbA1c < 6.5% at baseline and 7.57 (95% CI: 4.43-12.93) for 6.5% <= HbA1c <
      7% at baseline, compared to HbA1c < 4.5%. The risk of developing diabetes was
      1.14 (95% CI: 1.05-1.25) for male gender, 1.16 (95% CI: 1.04-1.28) for
      cardiovascular diseases and 2.06 (95% CI: 1.80-2.35) for overweight (BMI > 25
      kg/m(2)) at baseline. Neither age nor low socio-economic status was associated
      with increased risk of diabetes. CONCLUSION: Levels of HbA1c >= 5.5% were
      associated with increased risk of type 2 diabetes during a five-to-eight-year
      follow-up period. Findings support the use of HbA1c testing as a screening tool
      in populations at risk of developing diabetes.

PMID- 24286162
TI  - Deep venous thrombosis after major abdominal surgery in a Ugandan hospital: a
      prospective study.
AB  - BACKGROUND: Deep venous thrombosis (DVT) is a major cause of morbidity and
      mortality among postoperative patients. Its incidence has been reported to range
      between 16% and 38% among general surgery patients and may be as high as 60%
      among orthopaedic patients. The most important clinical outcome of DVT is
      pulmonary embolism, which causes about 10% of hospital deaths. In over 90% of
      patients, occurrence of DVT is silent and presents no symptoms until onset of
      pulmonary embolism and/or sudden death. The only effective way of guarding
      against this fatal condition is therefore prevention/prophylaxis. However,
      prophylaxis programs are usually based on the estimated prevalence of DVT in that
      particular community. There is currently no data concerning rates of
      postoperative DVT in Uganda.The purpose of the study was therefore to determine
      the prevalence of DVT among postoperative patients at Mulago Uganda's National
      Referral Hospital. METHODS: A cross sectional descriptive study was conducted
      between March and June 2011. Eligible patients were identified and screened and
      patient details were collected. Clinical examinations were done on postoperative
      days (PODs) 1, 2, and 4 and Doppler ultrasounds were done on POD 7 and POD 21 to
      assess for DVT. Patients found with DVT were treated appropriately according to
      local treatment guidelines. RESULTS: A total of 82 patients were recruited, 4/82
      (5%) had DVT. The most common risk factor was cancer. The overall mean age was 45
      years (range 20-83 years). The male to female ratio was 1.6:1. Participants with
      more than one risk factor for DVT were 16/82 (20%). CONCLUSIONS: Prevalence of
      DVT among major post-abdominal surgery patients was low (5%). Cancer was the most
      common associated factor apart from surgery.

PMID- 24286161
TI  - Proteomic analysis of membrane proteins of vero cells: exploration of potential
      proteins responsible for virus entry.
AB  - Vero cells are highly susceptible to many viruses in humans and animals, and its
      membrane proteins (MPs) are responsible for virus entry. In our study, the MP
      proteome of the Vero cells was investigated using a shotgun LC-MS/MS approach.
      Six hundred twenty-seven proteins, including a total of 1839 peptides, were
      identified in MP samples of the Vero cells. In 627 proteins, 307 proteins
      (48.96%) were annotated in terms of biological process of gene ontology (GO)
      categories; 356 proteins (56.78%) were annotated in terms of molecular function
      of GO categories; 414 proteins (66.03%) were annotated in terms of cellular
      components of GO categories. Of 627 identified proteins, seventeen proteins had
      been revealed to be virus receptor proteins. The resulting protein lists and
      highlighted proteins may provide valuable information to increase understanding
      of virus infection of Vero cells. 

PMID- 24286160
TI  - Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen
      species murine model of systemic sclerosis.
AB  - INTRODUCTION: Recent advances suggest that the cellular redox state may play a
      significant role in the progression of fibrosis in systemic sclerosis (SSc).
      Another, and as yet poorly accounted for, feature of SSc is its overlap with
      thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces
      oxidant stress. The aim of this study was therefore to evaluate the effect of
      propylthiouracil (PTU), and of the hypothyroidism induced by it, on the
      development of cutaneous and pulmonary fibrosis in the oxidant stress murine
      model of SSc. METHODS: Chronic oxidant stress SSc was induced in BALB/c mice by
      daily subcutaneous injections of hypochlorous acid (HOCl) for 6 weeks. Mice (n =
      25) were randomized into three arms: HOCl (n = 10), HOCl plus PTU (n = 10) or
      vehicle alone (n = 5). PTU administration was initiated 30 minutes after HOCl
      subcutaneous injection and continued daily for 6 weeks. Skin and lung fibrosis
      were evaluated by histologic methods. Immunohistochemical staining for alpha
      smooth muscle actin (alpha-SMA) in cutaneous and pulmonary tissues was performed
      to evaluate myofibroblast differentiation. Lung and skin concentrations of
      vascular endothelial growth factor (VEGF), extracellular signal-related kinase
      (ERK), rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforming
      growth factor (TGF) beta were analyzed by Western blot. RESULTS: Injections of
      HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTU treatment prevented
      both dermal and pulmonary fibrosis. Myofibroblast differentiation was also
      inhibited by PTU in the skin and lung. The increase in cutaneous and pulmonary
      expression of VEGF, ERK, Ras, and Rho in mice treated with HOCl was significantly
      prevented in mice co-administered with PTU. CONCLUSIONS: PTU, probably through
      its direct effect on reactive oxygen species or indirectly through thyroid
      function inhibition, prevents the development of cutaneous and pulmonary fibrosis
      by blocking the activation of the Ras-ERK pathway in the oxidant-stress animal
      model of SSc.

PMID- 24286163
TI  - Oviductal and endometrial mRNA expression of implantation candidate biomarkers
      during early pregnancy in rabbit.
AB  - Prenatal losses are a complex problem. Pregnancy requires orchestrated
      communication between the embryo and the uterus that includes secretions from the
      embryo to signal pregnancy recognition and secretion and remodelling from the
      uterine epithelium. Most of these losses are characterized by asynchronization
      between embryo and uterus. To better understand possible causes, an analysis was
      conducted of gene expression of a set of transcripts related to maternal
      recognition and establishment of rabbit pregnancy (uteroglobin, SCGB1A1; integrin
      alpha1, ITGA1; interferon-gamma, IFNG; vascular endothelial growth factor, VEGF)
      in oviduct and uterine tissue at 16, 72 or 144 h post-ovulation and insemination.
      In the oviduct tissue, a significant decrease in the level of SCGB1A1 mRNA
      expression was observed from 144 h post-ovulation. In the case of ITGA1, the
      transcript abundance was initially lower, but mRNA expression increased
      significantly at 72 and 144 h post-ovulation. For IFNG, a huge decrease was
      observed from 16 to 72 h post-ovulation. Finally, no significant differences were
      observed in the VEGF transcript. For the endometrium, the results showed a
      significant decline in the level of SCGB1A1 mRNA expression from 16 to 144 h post
      ovulation induction. The highest levels of ITGA1 transcript were detected at 144
      h, followed by the 16 h group and lower at 72 h post-ovulation. For IFNG there
      were no significant differences among post-ovulation induction times. Finally, it
      was possible to observe that VEGF mRNA abundance was present at low levels at 16
      h post-ovulation and remained low at 72 h, but increased at 144 h. The functional
      significance of these observations may provide new insights into the maternal
      role in prenatal losses. 

PMID- 24286164
TI  - Oxidative UO2 dissolution induced by soluble Mn(III).
AB  - The stability of UO2 is critical to the success of reductive bioremediation of
      uranium. When reducing conditions are no longer maintained, Mn redox cycling may
      catalytically mediate the oxidation of UO2 and remobilization of uranium. Ligand
      stabilized soluble Mn(III) was recently recognized as an important redox-active
      intermediate in Mn biogeochemical cycling. This study evaluated the kinetics of
      oxidative UO2 dissolution by soluble Mn(III) stabilized by pyrophosphate (PP) and
      desferrioxamine B (DFOB). The Mn(III)-PP complex was a potent oxidant that
      induced rapid UO2 dissolution at a rate higher than that by a comparable
      concentration of dissolved O2. However, the Mn(III)-DFOB complex was not able to
      induce oxidative dissolution of UO2. The ability of Mn(III) complexes to oxidize
      UO2 was probably determined by whether the coordination of Mn(III) with ligands
      allowed the attachment of the complexes to the UO2 surface to facilitate electron
      transfer. Systematic investigation into the kinetics of UO2 oxidative dissolution
      by the Mn(III)-PP complex suggested that Mn(III) could directly oxidize UO2
      without involving particulate Mn species (e.g., MnO2). The expected 2:1 reaction
      stoichiometry between Mn(III) and UO2 was observed. The reactivity of soluble
      Mn(III) in oxidizing UO2 was higher at lower ratios of pyrophosphate to Mn(III)
      and lower pH, which is probably related to differences in the ligand-to-metal
      ratio and/or protonation states of the Mn(III)-pyrophosphate complexes.
      Disproportionation of Mn(III)-PP occurred at pH 9.0, and the oxidation of UO2 was
      then driven by both MnO2 and soluble Mn(III). Kinetic models were derived that
      provided excellent fits of the experimental results. 

PMID- 24286165
TI  - Mechanical sensitization of cutaneous sensory fibers in the spared nerve injury
      mouse model.
AB  - BACKGROUND: The spared nerve injury (SNI) model of neuropathic pain produces
      robust and reproducible behavioral mechanical hypersensitivity. Although this
      rodent model of neuropathic pain has been well established and widely used,
      peripheral mechanisms underlying this phenotype remain incompletely understood.
      Here we investigated the role of cutaneous sensory fibers in the maintenance of
      mechanical hyperalgesia in mice post-SNI. FINDINGS: SNI produced robust, long
      lasting behavioral mechanical hypersensitivity compared to sham and naive
      controls beginning by post-operative day (POD) 1 and continuing through at least
      POD 180. We performed teased fiber recordings on single cutaneous fibers from the
      spared sural nerve using ex vivo skin-nerve preparations. Recordings were made
      between POD 16-42 after SNI or sham surgery. Adelta-mechanoreceptors (AM) and C
      fibers, many of which are nociceptors, from SNI mice fired significantly more
      action potentials in response to suprathreshold mechanical stimulation than did
      fibers from either sham or naive control mice. However, there was no increase in
      spontaneous activity. CONCLUSIONS: To our knowledge, this is the first study
      evaluating the contribution of primary afferent fibers in the SNI model. These
      data suggest that enhanced suprathreshold firing in AM and C fibers may play a
      role in the marked, persistent mechanical hypersensitivity observed in this
      model. These results may provide insight into mechanisms underlying neuropathic
      pain in humans.

PMID- 24286166
TI  - Development and assessment of floor and ceiling items for the PROMIS physical
      function item bank.
AB  - INTRODUCTION: Disability and Physical Function (PF) outcome assessment has had
      limited ability to measure functional status at the floor (very poor functional
      abilities) or the ceiling (very high functional abilities). We sought to
      identify, develop and evaluate new floor and ceiling items to enable broader and
      more precise assessment of PF outcomes for the NIH Patient-Reported-Outcomes
      Measurement Information System (PROMIS). METHODS: We conducted two cross
      sectional studies using NIH PROMIS item improvement protocols with expert review,
      participant survey and focus group methods. In Study 1, respondents with low PF
      abilities evaluated new floor items, and those with high PF abilities evaluated
      new ceiling items for clarity, importance and relevance. In Study 2, we compared
      difficulty ratings of new floor items by low functioning respondents and ceiling
      items by high functioning respondents to reference PROMIS PF-10 items. We used
      frequencies, percentages, means and standard deviations to analyze the data.
      RESULTS: In Study 1, low (n = 84) and high (n = 90) functioning respondents were
      mostly White, women, 70 years old, with some college, and disability scores of
      0.62 and 0.30. More than 90% of the 31 new floor and 31 new ceiling items were
      rated as clear, important and relevant, leaving 26 ceiling and 30 floor items for
      Study 2. Low (n = 246) and high (n = 637) functioning Study 2 respondents were
      mostly White, women, 70 years old, with some college, and Health Assessment
      Questionnaire (HAQ) scores of 1.62 and 0.003. Compared to difficulty ratings of
      reference items, ceiling items were rated to be 10% more to greater than 40% more
      difficult to do, and floor items were rated to be about 12% to nearly 90% less
      difficult to do. CONCLUSIONS: These new floor and ceiling items considerably
      extend the measurable range of physical function at either extreme. They will
      help improve instrument performance in populations with broad functional ranges
      and those concentrated at one or the other extreme ends of functioning. Optimal
      use of these new items will be assisted by computerized adaptive testing (CAT),
      reducing questionnaire burden and insuring item administration to appropriate
      individuals.

PMID- 24286168
TI  - Submissions bode well for 2014.

PMID- 24286167
TI  - Decreased expression of the endothelial cell-derived factor EGFL7 in systemic
      sclerosis: potential contribution to impaired angiogenesis and vasculogenesis.
AB  - INTRODUCTION: Microvascular damage and defective angiogenesis and vasculogenesis
      have a major role in the pathogenesis of systemic sclerosis (SSc). Epidermal
      growth factor-like domain 7 (EGFL7) is a proangiogenic molecule which is
      predominantly expressed and secreted by endothelial cells and their progenitors
      and controls vascular development and integrity. In this study, we investigated
      the possible involvement of EGFL7 in SSc. METHODS: Serum EGFL7 levels from 60
      patients with SSc and 35 age- and sex-matched healthy controls were examined by
      colorimetric sandwich enzyme-linked immunosorbent assay. The expression of EGFL7
      in forearm skin biopsies (n = 16 SSc, n = 10 controls), cultured dermal
      microvascular endothelial cells (MVECs) (n = 3 SSc, n = 3 controls) and late
      outgrowth peripheral blood endothelial progenitor cell (EPC)-derived endothelial
      cells (n = 15 SSc, n = 8 controls) was investigated by immunofluorescence and
      Western blotting. RESULTS: Serum EGFL7 levels were detectable in 68.6% of healthy
      controls and 45% of SSc cases (P < 0.05). Circulating levels of EGFL7 were
      significantly decreased in SSc patients compared with healthy controls (P =
      0.01). Serum levels of EGFL7 were significantly lower in both limited cutaneous
      SSc and diffuse cutaneous SSc patients than in controls (P = 0.02 and P = 0.04,
      respectively). In SSc, decreased serum EGFL7 levels were significantly correlated
      with the severity of nailfold capillary abnormalities. Patients with the most
      severe capillary changes and digital ulcers had serum EGFL7 levels significantly
      lower than healthy controls, while the EGFL7 levels did not differ significantly
      between controls and SSc patients with less capillary damage and lack of digital
      ulcers. Endothelial EGFL7 expression was strongly downregulated or even almost
      completely undetectable in SSc-affected dermis compared with controls (P <
      0.001). In cultured SSc dermal MVECs and late-outgrowth peripheral blood EPC
      derived endothelial cells, EGFL7 was significantly downregulated compared with
      cells obtained from healthy subjects (P < 0.01 and P < 0.001, respectively).
      CONCLUSIONS: Our findings suggest that the loss of EGFL7 expression in
      endothelial cells and their progenitors might play a role in the development and
      progression of peripheral microvascular damage and the defective vascular repair
      process characteristic of SSc.

PMID- 24286169
TI  - Two closely related members of Arabidopsis 13-lipoxygenases (13-LOXs), LOX3 and
      LOX4, reveal distinct functions in response to plant-parasitic nematode
      infection.
AB  - The responses of two closely related members of Arabidopsis 13-lipoxygenases (13
      LOXs), LOX3 and LOX4, to infection by the sedentary nematodes root-knot nematode
      (Meloidogyne javanica) and cyst nematode (Heterodera schachtii) were analysed in
      transgenic Arabidopsis seedlings. The tissue localization of LOX3 and LOX4 gene
      expression using beta-glucuronidase (GUS) reporter gene constructs showed local
      induction of LOX3 expression when second-stage juveniles reached the vascular
      bundle and during the early stages of plant-nematode interaction through gall and
      syncytia formation. Thin sections of nematode-infested knots indicated LOX3
      expression in mature giant cells, and high expression in neighbouring cells and
      those surrounding the female body. LOX4 promoter was also activated by nematode
      infection, although the GUS signal weakened as infection and disease progressed.
      Homozygous insertion mutants lacking LOX3 were less susceptible than wild-type
      plants to root-knot nematode infection, as reflected by a decrease in female
      counts. Conversely, deficiency in LOX4 function led to a marked increase in
      females and egg mass number and in the female to male ratio of M. javanica and H.
      schachtii, respectively. The susceptibility of lox4 mutants was accompanied by
      increased expression of allene oxide synthase, allene oxide cyclase and ethylene
      responsive transcription factor 4, and the accumulation of jasmonic acid,
      measured in the roots of lox4 mutants. This response was not found in lox3
      mutants. Taken together, our results reveal that LOX4 and LOX3 interfere
      differentially with distinct metabolic and signalling pathways, and that LOX4
      plays a major role in controlling plant defence against nematode infection. 

PMID- 24286170
TI  - Correlates of gut community composition across an ant species (Cephalotes
      varians) elucidate causes and consequences of symbiotic variability.
AB  - Insect guts are often colonized by multispecies microbial communities that play
      integral roles in nutrition, digestion and defence. Community composition can
      differ across host species with increasing dietary and genetic divergence, yet
      gut microbiota can also vary between conspecific hosts and across an individual's
      lifespan. Through exploration of such intraspecific variation and its correlates,
      molecular profiling of microbial communities can generate and test hypotheses on
      the causes and consequences of symbioses. In this study, we used 454
      pyrosequencing and TRFLP to achieve these goals in an herbivorous ant, Cephalotes
      varians, exploring variation in bacterial communities across colonies,
      populations and workers reared on different diets. C. varians bacterial
      communities were dominated by 16 core species present in over two-thirds of the
      sampled colonies. Core species comprised multiple genotypes, or strains and
      hailed from ant-specific clades containing relatives from other Cephalotes
      species. Yet three were detected in environmental samples, suggesting the
      potential for environmental acquisition. In spite of their prevalence and long
      standing relationships with Cephalotes ants, the relative abundance and genotypic
      composition of core species varied across colonies. Diet-induced plasticity is a
      likely cause, but only pollen-based diets had consistent effects, altering the
      abundance of two types of bacteria. Additional factors, such as host age,
      genetics, chance or natural selection, must therefore shape natural variation.
      Future studies on these possibilities and on bacterial contributions to the use
      of pollen, a widespread food source across Cephalotes, will be important steps in
      developing C. varians as a model for studying widespread social insect-bacteria
      symbioses. 

PMID- 24286171
TI  - Depressive symptoms in outpatients with heart failure: importance of inflammatory
      biomarkers, disease severity and personality.
AB  - OBJECTIVE: Depressive symptoms are highly prevalent in heart failure (HF)
      patients, however the underlying etiology of depression in HF patients remains
      yet unclear. Hence, the goal is to examine the relative importance of
      inflammation, disease severity and personality as predictors of depression in HF
      patients. DESIGN: Depressive symptoms (Hospital Anxiety and Depression Scale,
      depression subscale) were assessed at baseline and one-year follow-up in 268 HF
      patients (75.6% men; mean age = 66.7 +/- 8.7). Markers of inflammation (TNFalpha,
      sTNFr1, sTNFr2, IL-6 and IL-10), disease severity (e.g. New York Heart
      Association (NYHA) classification) and personality (Type D personality,
      loneliness) were assessed at baseline. RESULTS: At baseline, NYHA class, body
      mass index, educational level, Type D personality and loneliness were
      significantly associated with depression. Higher NYHA class (B = 2.25; SE = .83),
      higher educational level (B = 1.41; SE = .48), Type D personality (B = 2.56; SE =
      .60) and loneliness (B = .19; SE = .05) were also independently associated with
      higher depression levels at one-year follow-up (all p-values < .005).
      Inflammation, brain natriuretic peptide and left ventricular ejection fraction
      were not related to depression over time. CONCLUSIONS: Personality factors, but
      not inflammation, were independent concomitants of depressive symptoms in
      patients with HF. Gaining more insight into the etiology of depression in HF
      patients is important in order to identify potential targets for novel
      interventions.

PMID- 24286173
TI  - Full-length sequence of KIR3DL1*01501 allele found in Sub-Saharan Africa by long
      range sequencing.
AB  - Full-length KIR3DL1*01501 differing from KIR3DL1*0150201 with 10 SNPs and 2
      nucleotide deletion in intron 7. 

PMID- 24286174
TI  - Chronic stress mediators act synergistically on colonic nociceptive mouse dorsal
      root ganglia neurons to increase excitability.
AB  - BACKGROUND: Stress hormones can signal to colonic dorsal root ganglia (DRG)
      neurons and may play a role in sustained hyperexcitability of nociceptors.
      METHODS: Mouse DRG neurons were exposed overnight to epinephrine (Epi) 5 nM
      and/or corticosterone (Cort) 1 MUM or prior water-avoidance stress. Patch clamp
      recordings, visceromotor reflexes (VMRs) and molecular studies were conducted.
      KEY RESULTS: Water-avoidance stress induced neuronal hyperexcitability.
      Incubation of DRG neurons in both Cort and Epi (but neither alone) induced
      hyperexcitability (rheobase decreased 51%, p < 0.05; action potential discharge
      increased 95%, p < 0.01); this was blocked by antagonists of the beta2
      adrenoreceptor (butoxamine, But) and Cort receptor (mifepristone) in combination
      or alone. Stress hormones enhanced voltage-gated Nav 1.7 currents (p < 0.05) and
      suppressed IA (p < 0.0001) and IK+ (p < 0.05) currents. Furthermore, stress
      hormones increased DRG beta2 adrenoreceptor mRNA (59%, p = 0.007) and protein
      (125%, p < 0.05), also Nav 1.7 transcript (45%, p = 0.004) and protein (114%, p =
      0.002). In whole-animal studies, the WAS hyperexcitability of DRG neurons was
      blocked by antagonists of the beta2 and glucocorticoid receptors (GCR) but
      together they paradoxically increased VMRs to colorectal balloon distension.
      CONCLUSIONS & INFERENCES: Stress mediators Epi and Cort activate beta2 and GCR on
      DRG neurons which synergistically induce hyperexcitability of nociceptive DRG
      neurons and cause corresponding changes in voltage-gated Na(+) and K(+) currents.
      Furthermore, they increase the expression of beta2 adrenoreceptors and Nav1.7
      channels, suggesting transcriptional changes could contribute to sustained
      signaling following stress. The paradoxical effects of But and mifepristone in
      electrophysiological compared to VMR testing may reflect different peripheral and
      central actions on sensory signaling.

PMID- 24286172
TI  - L1 retrotransposons, cancer stem cells and oncogenesis.
AB  - Retrotransposons have played a central role in human genome evolution. The
      accumulation of heritable L1, Alu and SVA retrotransposon insertions continues to
      generate structural variation within and between populations, and can result in
      spontaneous genetic disease. Recent works have reported somatic L1
      retrotransposition in tumours, which in some cases may contribute to oncogenesis.
      Intriguingly, L1 mobilization appears to occur almost exclusively in cancers of
      epithelial cell origin. In this review, we discuss how L1 retrotransposition
      could potentially trigger neoplastic transformation, based on the established
      correlation between L1 activity and cellular plasticity, and the proven capacity
      of L1-mediated insertional mutagenesis to decisively alter gene expression and
      functional output. 

PMID- 24286175
TI  - Acute surgical unit: the Australasian experience.
AB  - BACKGROUND: The acute surgical unit (ASU) model of care is a new paradigm shift
      in the provision of emergency surgery. Clinical and non-clinical outcomes have
      been described after the introduction of the ASU model in Australia and New
      Zealand. This paper reviews and analyses the current published literature and
      methods of implementation of contemporary ASU models. METHOD: We conducted a
      comprehensive database search to identify all relevant published papers
      pertaining to the ASU. Included papers compared ASU models to emergency surgery's
      traditional model of care. Relevant clinical and non-clinical end points were
      extracted for analysis. RESULTS: Seven papers and two abstracts published data
      assessing clinical and non-clinical end points within the ASU. Four out of six
      studies reported a reduction in hospital length of stay. Two out of three studies
      showed reduction in mean time to emergency department review and two out of four
      studies reported a reduction in time to surgery. Additionally, four out of five
      studies showed a reduction in after hours operating with an ASU model.
      CONCLUSION: Trends in clinical outcomes are seen including reduced length of
      stay, time to emergency department assessment and surgery, supplemented by non
      clinical outcomes including reduced after hours operating and the potential for
      increased training opportunities. The published data presents certain weaknesses
      and further information is required to appreciate the applicability of certain
      aspects of the ASU model to smaller centres.

PMID- 24286176
TI  - Neuroprotective role of hydralazine in rat spinal cord injury-attenuation of
      acrolein-mediated damage.
AB  - Acrolein, an alpha,beta-unsaturated aldehyde and a reactive product of lipid
      peroxidation, has been suggested as a key factor in neural post-traumatic
      secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex
      vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the
      elevation lasted at least 2 weeks in a rat SCI model. More importantly,
      hydralazine, a known acrolein scavenger can provide neuroprotection when applied
      systemically. Besides effectively reducing acrolein, hydralazine treatment also
      resulted in significant amelioration of tissue damage, motor deficits, and
      neuropathic pain. This effect was further supported by demonstrating the ability
      of hydralazine to reach spinal cord tissue at a therapeutic level following
      intraperitoneal application. This suggests that hydralazine is an effective
      neuroprotective agent not only in vitro, but in a live animal model of SCI as
      well. Finally, the role of acrolein in SCI was further validated by the fact that
      acrolein injection into the spinal cord caused significant SCI-like tissue damage
      and motor deficits. Taken together, available evidence strongly suggests a
      critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since
      acrolein has been linked to a variety of illness and conditions, we believe that
      acrolein-scavenging measures have the potential to be expanded significantly
      ensuring a broad impact on human health.

PMID- 24286178
TI  - The COP9 signalosome subunit 6 (CSN6): a potential oncogene.
AB  - CSN6 is one subunit of the constitutive photomorphogenesis 9 (COP9) signalosome
      (CSN), which is an evolutionarily conserved multiprotein complex found in plants
      and animals and originally described as a repressor of light-dependent growth and
      transcription in Arabidopsis. CSN is homologous to the 19S lid subcomplex of the
      26S proteasome, thus it has been postulated to be a regulator of the ubiquitin
      proteasome pathway. In mammalian cells, it consists of eight subunits (CSN1
      CSN8). Among the CSN subunits, CSN5 and CSN6 are the only two that each contains
      an MPN (Mpr1p and Pad1p N-terminal) domain. The deneddylating activity of an MPN
      domain toward cullin-RING ubiquitin ligases (CRL) may coordinate CRL-mediated
      ubiquitination activity. More and more studies about CSN6 are emerging, and its
      overexpression is found in many types of cancers. Evidence has shown that CSN6 is
      a molecule platform between protein degradation and signal transduction. Here, we
      provide a summary of human CSN6, especially its roles in cancer, hoping that it
      can lay the groundwork for cancer prevention or therapy. 

PMID- 24286177
TI  - GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated
      by osteoarthritis-associated factors.
AB  - INTRODUCTION: Osteoarthritis is, at least in a subset of patients, associated
      with hypertrophic differentiation of articular chondrocytes. Recently, we
      identified the bone morphogenetic protein (BMP) and wingless-type MMTV
      integration site (WNT) signaling antagonists Gremlin 1 (GREM1), frizzled-related
      protein (FRZB) and dickkopf 1 homolog (Xenopus laevis) (DKK1) as articular
      cartilage's natural brakes of hypertrophic differentiation. In this study, we
      investigated whether factors implicated in osteoarthritis or regulation of
      chondrocyte hypertrophy influence GREM1, FRZB and DKK1 expression levels.
      METHODS: GREM1, FRZB and DKK1 mRNA levels were studied in articular cartilage
      from healthy preadolescents and healthy adults as well as in preserved and
      degrading osteoarthritic cartilage from the same osteoarthritic joint by
      quantitative PCR. Subsequently, we exposed human articular chondrocytes to WNT,
      BMP, IL-1beta, Indian hedgehog, parathyroid hormone-related peptide, mechanical
      loading, different medium tonicities or distinct oxygen levels and investigated
      GREM1, FRZB and DKK1 expression levels using a time-course analysis. RESULTS:
      GREM1, FRZB and DKK1 mRNA expression were strongly decreased in osteoarthritis.
      Moreover, this downregulation is stronger in degrading cartilage compared with
      macroscopically preserved cartilage from the same osteoarthritic joint. WNT, BMP,
      IL-1beta signaling and mechanical loading regulated GREM1, FRZB and DKK1 mRNA
      levels. Indian hedgehog, parathyroid hormone-related peptide and tonicity
      influenced the mRNA levels of at least one antagonist, while oxygen levels did
      not demonstrate any statistically significant effect. Interestingly, BMP and WNT
      signaling upregulated the expression of each other's antagonists. CONCLUSIONS:
      Together, the current study demonstrates an inverse correlation between
      osteoarthritis and GREM1, FRZB and DKK1 gene expression in cartilage and provides
      insight into the underlying transcriptional regulation. Furthermore, we show that
      BMP and WNT signaling are linked in a negative feedback loop, which might prove
      essential in articular cartilage homeostasis by balancing BMP and WNT activity.

PMID- 24286179
TI  - Development of ciclopirox olamine topical formulations: evaluation of drug
      release, penetration and cutaneous retention.
AB  - With the aim of reducing system absorption and consequently, the side effects,
      and simultaneously select a penetration enhancing, three topical formulations
      with 0.5% ciclopirox olamine (CO) and 15% of propylene glycol (PG),
      ethoxydiglycol or oleic acid were developed and evaluated regarding the skin
      penetration and cutaneous retention of the drug using Franz diffusion cells.
      Release experiments were performed through synthetic membrane while dermatomed
      pig ear skin was used to evaluate CO skin penetration and skin retention.
      Retention studies were carried out applying tape stripping method and dosing CO
      in stratum corneum and in epidermis and dermis. A HPLC method was validated for
      quantifying CO. All formulations tested with synthetic membrane presented no
      retention of the drug. Permeation data suggested that there was no systemic
      absorption of ciclopirox olamine from the studied formulations, even when the
      skin penetration enhancers were applied. Higher concentrations of the drug were
      found in the stratum corneum (SC) and also in epidermis and dermis, for all of
      the developed formulations. The addition of enhancers improved the penetration
      and cutaneous retention of CO, and propylene glycol promoted higher
      concentrations in epidermis and dermis, probably because its cumulative effect on
      the skin and by an efficient solvent power.

PMID- 24286180
TI  - Preterm dietary study: meal frequency, regurgitation and the surprisingly high
      use of laxatives among formula-fed infants following discharge.
AB  - AIM: To describe eating habits and possible feeding intolerance among preterm
      infants based on type of nutrition. METHODS: The parents of infants born below 32
      weeks filled in questionnaires, before and after discharge, about type of
      nutrition, number of meals, regurgitation, number of stools and laxative use.
      RESULTS: A total of 769 questionnaires based on 286 very preterm infants were
      completed, and 753 were included. At 40 weeks of corrected age, infants fed both
      fortified and unfortified human milk received more daily meals (mean 7.37 and
      7.57) than preterm formula-fed infants (mean 6.79) (p < 0.05). Fortification of
      human milk did not seem to increase the incidence of regurgitation. Between 38.7
      and 42.9% of the preterm infants were treated with laxatives from discharge to 6
      months of corrected age. Infants fed preterm formula prior to discharge, at term,
      at 2 and 4 months of corrected age received laxatives more often than infants fed
      human milk, with odds ratios of 13.7, 137.5, 49.7 and 40.5, respectively (p <=
      0.001). CONCLUSION: Constipation seems to be frequent among very preterm infants.
      Laxative use averaged 40% across all the different feeding groups and was as high
      as 70-85% in formula-fed preterm infants over the course of the study.

PMID- 24286181
TI  - Effects of several anti-glaucoma medications on the circadian intraocular
      pressure fluctuations in patients with primary open-angle glaucoma.
AB  - PURPOSE: The purpose of the present study was to elucidate the effects of several
      anti-glaucoma medications on the circadian intraocular pressure (IOP)
      fluctuations in patients with primary open-angle glaucoma (POAG). PATIENTS AND
      METHODS: POAG patients (n=61; 61 eyes) with or without glaucoma medications were
      included. IOP measurement at 14 time points (12, 15, 18, 21, 0, 6, 9, 12, 15, 18,
      21, 0, 6, and 9 o'clock) was performed over a period of 48 h. IOP changes
      occurring in the first 24 h and the subsequent 24 h were evaluated by several
      therapeutic factors. RESULTS: A nocturnal acrophase pattern was observed in all
      the eyes with POAG. The shape of the first 24 h IOP curve was similar to that of
      the following 24 h IOP curves. However, there were fewer overall IOP levels in
      the second 24 h time period. Circadian IOP fluctuation patterns exhibited in each
      eye on the 1st and 2nd days were single acrophase patterns: diurnal acrophase
      (1st day, 54.0%; 2nd day, 60.7%) and nocturnal acrophase (1st day, 36.1%; 2nd
      day, 31.1%), and no single acrophase patterns: flat (1st day, 6.6%; 2nd day,
      4.9%) and double acrophase (1st day, 3.3%; 2nd day, 3.3%). Among the different
      medication groups, a nocturnal acrophase circadian pattern was observed in the
      patient groups being treated by combinations of prostaglandin analog (PG) and
      beta blocker or PG, beta blocker and carbonic anhydrase inhibitor (CAI). However,
      this was not apparent in patient groups with or without single anti-glaucoma
      medications or a combination of PG and CAI. CONCLUSIONS: The present study of IOP
      monitoring patients with POAG over a period of 48 h indicated that their changes
      in circadian patterns of IOP were affected by types of anti-glaucoma medications.

PMID- 24286182
TI  - Development of a simple and rapid method for the specific identification of
      organism causing anthrax by slide latex agglutination.
AB  - A specific latex agglutination test (LAT) based on anti-PA (protective antigen)
      antibodies having detection limit of 5 * 10(4) formalin treated Bacillus
      anthracis cells or 110 ng of PA was optimized in this study. The optimized LAT
      could detect anthrax toxin in whole blood as well as in serum from the animal
      models of anthrax infection. The protocol is a simple and promising method for
      the specific detection of bacteria causing anthrax under routine laboratory, as
      well as in field, conditions without any special equipments or expertise.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The article presents the first report of a
      latex agglutination test for the specific identification of the cultures of
      bacteria causing anthrax. As the test is targeting one of anthrax toxic protein
      (PA), this can also be used to determine virulence of suspected organisms. At the
      same time, the same LAT can be used directly on whole blood or sera samples under
      field conditions for the specific diagnosis of anthrax.

PMID- 24286183
TI  - Nasal in-situ gels for delivery of rasagiline mesylate: improvement in
      bioavailability and brain localization.
AB  - Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for
      effective treatment of Parkinson's disease. Intranasal gels were prepared by
      combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers
      (carbopol 934 P and chitosan). The formulations were evaluated for sol-gel
      transition temperature, in-vitro drug release and in-vivo mucociliary transit
      time. Further, optimal intranasal gel formulations were tested for in-vivo
      pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was
      found that optimal formulations had acceptable gelation temperature (28-33 
      degrees C) and adequate in-vitro drug release profile. Pharmacokinetic study in
      rabbits showed significant (p < 0.05) improvement in bioavailability (four- to
      six-folds) of the drug from intranasal gels than oral solution. Chronic exposure
      studies in Wistar rats showed that these intranasal gels were non-irritant and
      non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed
      significant (p < 0.01) improvement in uptake of RM form intranasal gel
      formulations than nasal solution.

PMID- 24286184
TI  - Comment on G. Herranz: The timing of monozygotic twinning: a criticism of the
      common model. Zygote (2013).

PMID- 24286186
TI  - Predicting hexadecane-air equilibrium partition coefficients (L) using a group
      contribution approach constructed from high quality data.
AB  - A group contribution-based quantitative structure-property relationship (QSPR)
      for the hexadecane-air equilibrium partition coefficients (L) of organic
      chemicals is developed using the iterative fragment selection (IFS) approach.
      This new QSPR includes in its training and external validation data sets L values
      for a large number of structurally complex chemicals measured by the same group
      using consistent methods. The resulting QSPR has better predictive power than
      other prediction methods trained primarily using data for chemicals of simpler
      structures, and measurements of L values from diverse sources. For a subset of
      chemicals in which the L values have non-additive effects caused by
      intramolecular hydrogen bonds, the new QSPR gives much better performance in
      comparison to the most commonly used prediction method. 

PMID- 24286187
TI  - Lipid signalling in health and disease.
AB  - This series of reviews is based on the FEBS Advanced Course on 'Lipid Signaling
      and Cancer' (4-10 October 2012, Vico Equense, Italy). The course encompassed the
      relationships between studies of basic and more translational aspects on the
      prevalence of altered lipid metabolism in different cancer types with a
      particular focus on phosphoinositides and sphingolipids. The reviews highlight
      both the basic aspects of these lipid classes and their roles in cancer
      development, and their potential as drug targets in cancer treatment. 

PMID- 24286185
TI  - Translational evidence for the involvement of the endocannabinoid system in
      stress-related psychiatric illnesses.
AB  - Accumulating evidence over the past decade has highlighted an important role of
      the endocannabinoid (eCB) system in the regulation of stress and emotional
      behavior across divergent species, from rodents to humans. The general findings
      from this work indicate that the eCB system plays an important role in gating and
      buffering the stress response, dampening anxiety and regulating mood. Work in
      rodents has allowed researchers to determine the neural mechanisms mediating this
      relationship while work in human populations has demonstrated the possible
      importance of this system in stress-related psychiatric diseases, such as post
      traumatic stress disorder, generalized anxiety and major depression. These stress
      protective effects of eCB signaling appear to be primarily mediated by their
      actions within corticolimbic structures, particularly the amygdala and the
      prefrontal cortex. The aim of this review is to provide an up-to-date discussion
      of the current level of knowledge in this field, as well as address the current
      gaps in knowledge and specific areas of research that require attention. 

PMID- 24286188
TI  - Understanding the photophysics of the spinach-DFHBI RNA aptamer-fluorogen complex
      to improve live-cell RNA imaging.
AB  - The use of aptamer-fluorogen complexes is an emerging strategy for RNA imaging.
      Despite its promise for cellular imaging and sensing, the low fluorescence
      intensity of the Spinach-DFHBI RNA aptamer-fluorogen complex hampers its utility
      in quantitative live-cell and high-resolution imaging applications. Here we
      report that illumination of the Spinach-fluorogen complex induces photoconversion
      and subsequently fluorogen dissociation, leading to fast fluorescence decay and
      fluorogen-concentration-dependent recovery. The fluorescence lifetime of Spinach
      DFHBI is 4.0 +/- 0.1 ns irrespective of the extent of photoconversion. We detail
      a low-repetition-rate illumination scheme that enables us to maximize the
      potential of the Spinach-DFHBI RNA imaging tag in living cells. 

PMID- 24286190
TI  - Elevated serum anti-flagellin antibodies implicate subclinical bowel inflammation
      in ankylosing spondylitis: an observational study.
AB  - INTRODUCTION: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD)
      share genetic and clinical features. IBD is associated with the presence of
      antibodies to a variety of commensal microorganisms including anti-Saccharomyces
      cerevesiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), anti
      I2 (associated with anti-Pseudomonas activity), anti-Eschericia coli outer
      membrane porin C (anti-OmpC) and anti-flagellin antibodies (anti-CBir1).
      Subclinical intestinal inflammation may be present in up to 65% of patients with
      AS. This study evaluated the presence of antimicrobial antibodies in patients
      with AS alone, patients with AS and concomitant IBD (AS-IBD) and a control group
      of patients with mechanical back pain (MBP). METHODS: Sera were tested by ELISA
      for ASCA IgG and IgA, anti-OmpC, anti-CBir1 and ANCA in 76 patients with AS
      alone, 77 patients with AS-IBD and 48 patients with MBP. Antibody positivity
      rates, median quantitative antibody levels and the proportion of patients with
      antibody levels in the 4th quartile of a normal distribution were compared
      between the three groups of patients. RESULTS: Patients with AS alone
      demonstrated higher anti-CBir1 antibody positivity rates and median antibody
      levels than MBP patients. Anti-CBir1 positivity in AS was associated with
      elevation of acute phase reactants. AS-IBD patients demonstrated elevated
      responses when compared to AS alone for ASCA, anti-OmpC and anti-CBir1. Quartile
      analysis confirmed the findings. CONCLUSIONS: These data suggest that adaptive
      immune responses to microbial antigens occur in AS patients without clinical IBD
      and support the theory of mucosal dysregulation as a mechanism underlying the
      pathophysiology of AS.

PMID- 24286189
TI  - HLA and non-HLA genes in Behcet's disease: a multicentric study in the Spanish
      population.
AB  - INTRODUCTION: According to genome wide association (GWA) studies as well as
      candidate gene approaches, Behcet's disease (BD) is associated with human
      leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been
      consistently associated with the disease, but the role of other HLA class I
      molecules remains controversial. Recently, variants in non-HLA genes have also
      been associated with BD. The aims of this study were to further investigate the
      influence of the HLA region in BD and to explore the relationship with non-HLA
      genes recently described to be associated in other populations. METHODS: This
      study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA
      B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single
      nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously
      described associated with the disease in GWA studies and having a minor allele
      frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays.
      Phenotypic and genotypic frequencies were estimated by direct counting and
      distributions were compared using the chi(2) test. RESULTS: In addition to HLA
      B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be
      protective. Other HLA-A and B specificities were suggestive of association with
      the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58).
      Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs
      in IL10 were found to be significantly associated with susceptibility to BD in
      our population. CONCLUSION: Different HLA specificities are associated with
      Behcet's disease in addition to B*51. Other non-HLA genes, such as IL23R and IL
      10, play a role in the susceptibility to the disease.

PMID- 24286191
TI  - Long-term outcomes after deceased donor renal transplantation in patients with
      genitourinary tuberculosis.

PMID- 24286192
TI  - Levonorgestrel-impregnated intrauterine device as treatment for endometrial
      hyperplasia: a national multicentre randomised trial.
AB  - OBJECTIVE: The purpose of this study was to investigate if the levonorgestrel
      impregnated intrauterine device (LNG-IUS, Mirena((r)) ) is safe and effective as
      therapy for low-risk and medium-risk endometrial hyperplasia compared with oral
      medroxyprogesterone (MPA). DESIGN: A multicentre randomised trial. SETTING:
      Norway. POPULATION: In all, 170 women aged 30-70 years with low- or medium-risk
      endometrial hyperplasia who met inclusion criteria. METHODS: Patients were
      randomly assigned to one of three treatment arms: LNG-IUS; oral MPA 10 mg
      administered for 10 days per cycle, or continuous oral MPA 10 mg daily, for 6
      months. MAIN OUTCOME MEASURES: The primary outcome measure was normalisation or
      persisting hyperplasia. RESULTS: After 6 months all three treatment regimens
      showed significant effect when the outcome was evaluated as therapy response or
      not (P < 0.001). Responses were obtained for all the women in the LNG-IUS group
      (53/53, 95% CI 0.93-1.0) and for 96% of the women in the continuous oral group
      (46/48, 95% CI 0.86-0.99). Only 69% of the women in the cyclic oral group were
      responders (36/52, 95% CI 0.55-0.81). Adverse effects were relatively common with
      minimal differences between therapy groups. CONCLUSION: In the first trial of its
      kind, women treated with the LNG-IUS showed histologically normal endometrium
      after 6 months of therapy for endometrial hyperplasia. Cyclical progestogens are
      found to be less effective compared with continuous oral therapy and LNG-IUS and
      should not be used for this purpose.

PMID- 24286193
TI  - Congenital platelet disorders and understanding of platelet function.
AB  - Genetic defects of platelets constitute rare diseases that include bleeding
      syndromes of autosomal dominant, recessive or X-linked inheritance. They affect
      platelet production, resulting in a low circulating platelet count and changes in
      platelet morphology, platelet function, or a combination of both with altered
      megakaryopoiesis and a defective platelet response. As a result, blood platelets
      fail to fulfil their haemostatic function. Most studied of the platelet function
      disorders are deficiencies of glycoprotein mediators of adhesion and aggregation
      while defects of primary receptors for stimuli include the P2Y12 ADP receptor.
      Studies on inherited defects of (i) secretion from storage organelles (dense
      granules, alpha-granules), (ii) the platelet cytoskeleton and (iii) the
      generation of pro-coagulant activity have identified genes indirectly controlling
      the functional response. Signalling pathway defects leading to agonist-specific
      modifications of platelet aggregation are the current target of exome-sequencing
      strategies. We now review recent advances in the molecular characterization of
      platelet function defects. 

PMID- 24286195
TI  - Are there associations among physical activity, fatigue, sleep quality and pain
      in people with mental illness? A pilot study.
AB  - Good mental health is imperative to well-being. Symptoms of fatigue, chronic pain
      and poor sleep are common in people with mental illness and contribute to
      substantial loss of functioning. Physical exercise interventions have shown to
      decrease these symptoms in a range of populations; however, their possible
      association with physical activity related to day-to-day functioning have not
      been explored in people hospitalized with severe mental illness. Inpatients (n =
      4) of a metropolitan mental health facility were fitted with an Actiwatch, which
      collected physical activity and sleep measures for an anticipated 14-day data
      collection period. During this time, morning and evening pain and fatigue scores
      were collected on an 11-point numerical rating scale. Significant associations
      were found between morning pain and morning fatigue scores (beta = -0.44, P =
      0.023), morning pain and physical activity (beta = 12.34, P = 0.042), and
      physical activity and evening pain scores (beta = 0.20, P = 0.017). Fatigue
      tended towards interfering more with quality of life than did pain, but this was
      not significant (P = 0.07). This study provided preliminary data suggesting
      associations between pain and fatigue, and intensity of pain and physical
      activity levels. This information can be used to generate hypotheses for future
      clinical trials.

PMID- 24286194
TI  - alpha5beta1 integrin induces the expression of noncartilaginous procollagen gene
      expression in articular chondrocytes cultured in monolayers.
AB  - INTRODUCTION: Articular chondrocytes undergo an obvious phenotypic change when
      cultured in monolayers. During this change, or dedifferentiation, the expression
      of type I and type III procollagen is induced where normal chondrocytes express
      little type I and type III procollagen. In this study, we attempted to determine
      the mechanism(s) for the induction of such procollagen expression in
      dedifferentiating chondrocytes. METHODS: All experiments were performed using
      primary-cultured human articular chondrocytes under approval of institutional
      review boards. Integrin(s) responsible for the induction of type I and type III
      procollagen expression were specified by RNAi experiments. The signal pathway(s)
      involved in the induction were determined by specific inhibitors and RNAi
      experiments. Adenovirus-mediated experiments were performed to identify a small
      GTPase regulating the activity of integrins in dedifferentiating chondrocytes.
      The effect of inhibition of integrins on dedifferentiation was investigated by
      experiments using echistatin, a potent disintegrin. The effect of echistatin was
      investigated first with monolayer-cultured chondrocytes, and then with pellet
      cultured chondrocytes. RESULTS: In dedifferentiating chondrocytes, alpha5beta1
      integrin was found to be involved in the induction of type I and type III
      procollagen expression. The induction was known to be mediated by v-akt murine
      thymoma viral oncogene homolog (AKT) signaling. Among the three AKT isoforms,
      AKT1 seemed to be most involved in the signaling. Elated RAS viral (r-ras)
      oncogene homolog (RRAS) was considered to regulate the progression of
      dedifferentiation by modulating the affinity and avidity of alpha5beta1 integrin
      to ligands. Echistatin inhibited dedifferentiation of monolayer-cultured
      chondrocytes. Furthermore, the matrix formed by pellet-cultured chondrocytes more
      closely resembled that of normal cartilage compared with the controls.
      CONCLUSIONS: The result of this study has shown, for the first time, that
      alpha5beta1 integrin may be responsible for the induction of non-cartilaginous
      collagen expression in chondrocytes undergoing dedifferentiation. Again, this
      study has shown that the inhibition of ligand ligation to integrins may be an
      effective strategy to inhibit phenotypic change of cultured chondrocytes, and to
      improve the quality of matrix synthesized by primary cultured chondrocytes.

PMID- 24286197
TI  - Improving stroke outcomes in rural areas through telestroke programs: an
      examination of barriers, facilitators, and state policies.
AB  - INTRODUCTION: Every year in the United States more than 600,000 ischemic stroke
      patients do not receive proven, effective stroke treatment or may not be
      medically eligible to receive the one medication endorsed by the U.S. Food and
      Drug Administration for acute ischemic stroke. The lack of treatment is due
      partly to shortages of neurological experts in rural and underserved areas.
      Telestroke programs can improve stroke care for stroke patients in rural and
      underserved settings by using interactive telecommunication technology that
      connects centrally located neurological experts to rural healthcare facilities.
      Many states have enacted policies and practices that facilitate telestroke
      access. MATERIALS AND METHODS: We reviewed statutes and regulations in all 50
      states that affect the adoption of telemedicine programs and describe examples of
      state-implemented programs in two states with policies that encourage telestroke
      use. RESULTS AND DISCUSSION: This review presents evidence of the value and
      effectiveness of telestroke programs, as well as an explanation of common
      barriers and facilitators of telestroke, including licensing and credentialing
      rules, reimbursement issues, and liability concerns. Most states have adopted
      policies that affect the adoption of telestroke programs. Georgia and South
      Carolina are examples of states implementing stroke policies using a telestroke
      model to treat stroke patients in rural areas.

PMID- 24286198
TI  - Randomized controlled trial of laparoscopic anterior 180 degrees  partial versus
      posterior 270 degrees  partial fundoplication.
AB  - BACKGROUND: Previous trials show good outcomes following anterior and posterior
      partial versus Nissen fundoplication for gastro-oesophageal reflux. However, it
      is unclear which partial fundoplication performs best. This study compared
      anterior 180 degrees  versus posterior 270 degrees  fundoplication. METHODS: At
      three hospitals, patients were randomized to anterior 180 degrees  versus
      posterior 270 degrees  partial fundoplication, and clinical outcomes were
      determined using a structured questionnaire at 3, 6 and 12 months. Heartburn,
      dysphagia and satisfaction were assessed using 0-10 analoue scales, and adverse
      outcomes and side effects were determined. Endoscopy, manometry and pH monitoring
      were performed 6 months after surgery. RESULTS: Forty-seven patients were
      randomized to anterior (n = 23) versus posterior (n = 24) fundoplication.
      Clinical outcomes for 93-98% of patients were available at each follow-up point.
      At 12 months, the mean heartburn score was higher following anterior
      fundoplication (2.7 versus 0.8, P = 0.045), although differences were not
      significant at earlier follow-up. Conversely, following posterior fundoplication,
      patients were less able to belch at 3 (56% versus 16%, P = 0.013) and 6 months
      (43% versus 9%, P = 0.017). No significant differences were demonstrated for
      dysphagia. Both groups had high rates of satisfaction with the outcome - 85%
      versus 86% satisfied at 12 months follow-up. CONCLUSION: Both partial
      fundoplications are effective treatments for gastro-oesophageal reflux. Posterior
      partial fundoplication is associated with less reflux symptoms offset by more
      side effects.

PMID- 24286199
TI  - Silver nanoparticle inhibition of polycyclic aromatic hydrocarbons degradation by
      Mycobacterium species RJGII-135.
AB  - Polycyclic aromatic hydrocarbons (PAH) are a common environmental contaminant
      originating from both anthropogenic and natural sources. Mycobacterium species
      are highly adapted to utilizing a variety of PAH. Silver nanoparticles (AgNP) are
      an emerging contaminant that possess bactericidal properties, interferes with the
      bacterial membrane and alters function. Mycobacterium sp. strain RJGII-135
      provided a model bacterium to assess changes in carbon metabolism by focusing on
      PAH degradation, which is dependent upon passive uptake of hydrophobic molecules
      into the cell membrane. A mixture of 18 PAH served as a complex mixture of carbon
      sources for assessing carbon metabolism. At environmentally relevant PAH
      concentrations, RJGII-135 degraded two-, three-, and four-ring PAH within 72 h,
      but preferentially attacked phenanthrene and fluorene. Total cell growth and PAH
      degradation were successively reduced when exposed to 0.05-0.5 mg 1(-1) AgNP.
      However, 0.05 mg l(-1) AgNP inhibited degradation of naphthalene, acenaphthylene
      and acenaphthalene. RJGII-135 retained the ability to degrade the methylated
      naphthalenes regardless of AgNP concentration suggesting that proteins involved
      in dihydrodiol formation were inhibited. The reduced PAH metabolism of RJGII-135
      when exposed to sublethal concentrations of AgNP provides evidence that
      nanoparticle pollution could alter carbon cycling in soils, sediment and aquatic
      environments. SIGNIFICANCE AND IMPACT OF THE STUDY: Silver nanoparticle (AgNP)
      pollution threatens bacterial-mediated processes due to their antibacterial
      properties. With the widespread commercial use of AgNP, continued environmental
      release is inevitable and we are just beginning to understand the potential
      environmental ramifications of nanoparticle pollution. This study examined AgNP
      inhibition of carbon metabolism through the polycyclic aromatic hydrocarbon
      degradation by Mycobacterium species RJGII-135. Sublethal doses altered PAH
      metabolism, which is dependent upon cell membrane properties and intracellular
      proteins. The changed carbon metabolism when exposed to sublethal doses of AgNP
      suggests broad impacts of this pollution on bacterial carbon cycling in diverse
      environments.

PMID- 24286196
TI  - Interdisciplinary collaborative team for blastocyst implantation research:
      inception and perspectives.

PMID- 24286200
TI  - Restaging locally advanced rectal cancer by different imaging modalities after
      preoperative chemoradiation: a comparative study.
AB  - BACKGROUND: To compare the accuracy of different imaging modalities, alone and in
      combination in predicting findings at surgery after preoperative chemoradiation
      for locally advanced rectal cancer. METHODS: Following chemoradiation, tumors
      were reclassified on the basis of findings on pelvic computed tomography (CT) (94
      patients), endorectal ultrasonography (EUS) (138 patients) alone or by both CT
      and EUS (80 patients). The ability of the imaging modalities, to predict the
      pathologic T status, N status, and TNM stage at surgery was evaluated and
      compared. RESULTS: Mean age of the patients was 64.5 years (range 28-88 years);
      55% were male. CT and EUS combined had a positive predictive value of 20% for
      pathologic pT1 stage, 29% for pT1, 29% for pT2, and 58% for pT3. Predictive
      values for the operative TNM stage were 50% for stage I, 45% for stage II, and
      31% for stage III. These values did not exceed those for each modality alone.
      CONCLUSION: The performance of preoperative CT and EUS in predicting the T and
      TNM stage of rectal cancer at surgery is poor. Neither modality alone nor the two
      combined is sufficiently accurate to serve as the basis for decisions regarding
      treatment modification.

PMID- 24286201
TI  - Serious periventricular white matter injury has a significant effect on the
      voiding pattern of preterm infants.
AB  - AIM: To evaluate the effect of serious periventricular white matter injury (PWMI)
      on the voiding patterns of preterm infants. METHODS: Free voiding was
      continuously observed for eight hours in 19 preterm infants with serious PWMI and
      16 infants without PWMI. The infants had a gestational age of 32-35 weeks and a
      postnatal age of 9-15 days. Voiding frequency, voided volume, postvoid residual
      volume, empty voiding, awake voiding and interrupted voiding were recorded and
      compared between the two groups of infants. RESULTS: The voiding frequency ((5.1
      +/- 1.0) vs. (7.0 +/- 1.1)), awake voiding percentage ((23 +/- 11)% vs. (42 +/-
      7)%) and empty voiding percentage (lower quartile = 16% vs. 28%, median = 20% vs.
      33%, upper quartile = 28% vs. 40%) were significantly lower, while the voided
      volume ((19.9 +/- 6.6) mL vs.(15.9 +/- 5.3) mL)and postvoid residual volume
      (lower quartile = 1 mL. vs. 0 mL., median = 3 mL. vs. 2 mL., upper quartile = 3
      mL. vs. 2 mL.) were significantly higher in the injured preterm infants, compared
      with the healthy infants (p < 0.05). CONCLUSION: Serious PWMI has a significant
      effect on the voiding pattern of preterm infants, and the senior nerve centre
      plays a role in the voiding reflex of preterm infants.

PMID- 24286202
TI  - An interdisciplinary checklist for left ventricular assist device deactivation.

PMID- 24286203
TI  - Palliative surgery in the multidisciplinary management of advanced ovarian
      cancer.

PMID- 24286204
TI  - From cradle of European civilization to grave austerity: does Greece face a
      creeping health disaster?

PMID- 24286205
TI  - An analysis of geothermal and carbonic springs in the western United States
      sustained by deep fluid inputs.
AB  - Hydrothermal springs harbor unique microbial communities that have provided
      insight into the early evolution of life, expanded known microbial diversity, and
      documented a deep Earth biosphere. Mesothermal (cool but above ambient
      temperature) continental springs, however, have largely been ignored although
      they may also harbor unique populations of micro-organisms influenced by deep
      subsurface fluid mixing with near surface fluids. We investigated the microbial
      communities of 28 mesothermal springs in diverse geologic provinces of the
      western United States that demonstrate differential mixing of deeply and
      shallowly circulated water. Culture-independent analysis of the communities
      yielded 1966 bacterial and 283 archaeal 16S rRNA gene sequences. The springs
      harbored diverse taxa and shared few operational taxonomic units (OTUs) across
      sites. The Proteobacteria phylum accounted for most of the dataset (81.2% of all
      16S rRNA genes), with 31 other phyla/candidate divisions comprising the
      remainder. A small percentage (~6%) of bacterial 16S rRNA genes could not be
      classified at the phylum level, but were mostly distributed in those springs with
      greatest inputs of deeply sourced fluids. Archaeal diversity was limited to only
      four springs and was primarily composed of well-characterized Thaumarchaeota.
      Geochemistry across the dataset was varied, but statistical analyses suggested
      that greater input of deeply sourced fluids was correlated with community
      structure. Those with lesser input contained genera typical of surficial waters,
      while some of the springs with greater input may contain putatively
      chemolithotrophic communities. The results reported here expand our understanding
      of microbial diversity of continental geothermal systems and suggest that these
      communities are influenced by the geochemical and hydrologic characteristics
      arising from deeply sourced (mantle-derived) fluid mixing. The springs and
      communities we report here provide evidence for opportunities to understand new
      dimensions of continental geobiological processes where warm, highly reduced
      fluids are mixing with more oxidized surficial waters. 

PMID- 24286206
TI  - Preparation, characterization and in vitro evaluation of sterically stabilized
      liposome containing a naphthalenediimide derivative as anticancer agent.
AB  - The aim of this study was to incorporate a new naphthalenediimide derivative
      (AN169) with a promising anticancer activity into pegylated liposomes to an
      extent that allows its in vitro and in vivo testing without use of toxic solvent.
      AN169-loaded liposomes were prepared using the thin-film hydration method and
      characterized for size, polydispersity index, drug content and drug release. We
      examined their lyophilization ability in the presence of cryoprotectants
      (trehalose, sucrose and lysine) and the long-term stability of the lyophilized
      products stored at 4  degrees C for 3 and 6 months by particle size changes and
      drug leakage. AN169 was successfully loaded into liposomes with an entrapment
      efficiency of 87.3 +/- 2.5%. The hydrodynamic diameter of these liposomes after
      sonication was ~ 145 nm with a high degree of monodispersity. Trehalose was found
      to be superior to the other lyoprotectants. In particular, trehalose 1:10
      lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with
      the conservation of physicochemical properties upon freeze-drying and long-term
      storage conditions. We also assessed their in vitro antitumor activity in human
      cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian
      carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation,
      loaded liposomes showed almost the same IC50 as free AN169. In conclusion, we
      developed a stable lyophilized liposomal formulation for intravenous
      administration of AN169 as anticancer drug, with the advantage of avoiding the
      use of potentially toxic solubilizing agents for future in vivo experiments.

PMID- 24286207
TI  - Controlled-deactivation cannabinergic ligands.
AB  - We report an approach for obtaining novel cannabinoid analogues with controllable
      deactivation and improved druggability. Our design involves the incorporation of
      a metabolically labile ester group at the 2'-position on a series of (-)-Delta(8)
      THC analogues. We have sought to introduce benzylic substituents alpha to the
      ester group which affect the half-lives of deactivation through enzymatic
      activity while enhancing the affinities and efficacies of individual ligands for
      the CB1 and CB2 receptors. The 1'-(S)-methyl, 1'-gem-dimethyl, and 1'-cyclobutyl
      analogues exhibit remarkably high affinities for both CB receptors. The novel
      ligands are susceptible to enzymatic hydrolysis by plasma esterases in a
      controllable manner, while their metabolites are inactive at the CB receptors. In
      further in vitro and in vivo experiments key analogues were shown to be potent
      CB1 receptor agonists and to exhibit CB1-mediated hypothermic and analgesic
      effects. 

PMID- 24286208
TI  - Risk of bias: a simulation study of power to detect study-level moderator effects
      in meta-analysis.
AB  - BACKGROUND: There are both theoretical and empirical reasons to believe that
      design and execution factors are associated with bias in controlled trials.
      Statistically significant moderator effects, such as the effect of trial quality
      on treatment effect sizes, are rarely detected in individual meta-analyses, and
      evidence from meta-epidemiological datasets is inconsistent. The reasons for the
      disconnect between theory and empirical observation are unclear. The study
      objective was to explore the power to detect study level moderator effects in
      meta-analyses. METHODS: We generated meta-analyses using Monte-Carlo simulations
      and investigated the effect of number of trials, trial sample size, moderator
      effect size, heterogeneity, and moderator distribution on power to detect
      moderator effects. The simulations provide a reference guide for investigators to
      estimate power when planning meta-regressions. RESULTS: The power to detect
      moderator effects in meta-analyses, for example, effects of study quality on
      effect sizes, is largely determined by the degree of residual heterogeneity
      present in the dataset (noise not explained by the moderator). Larger trial
      sample sizes increase power only when residual heterogeneity is low. A large
      number of trials or low residual heterogeneity are necessary to detect effects.
      When the proportion of the moderator is not equal (for example, 25% 'high
      quality', 75% 'low quality' trials), power of 80% was rarely achieved in
      investigated scenarios. Application to an empirical meta-epidemiological dataset
      with substantial heterogeneity (I(2) = 92%, tau(2) = 0.285) estimated >200 trials
      are needed for a power of 80% to show a statistically significant result, even
      for a substantial moderator effect (0.2), and the number of trials with the less
      common feature (for example, few 'high quality' studies) affects power
      extensively. CONCLUSIONS: Although study characteristics, such as trial quality,
      may explain some proportion of heterogeneity across study results in meta
      analyses, residual heterogeneity is a crucial factor in determining when
      associations between moderator variables and effect sizes can be statistically
      detected. Detecting moderator effects requires more powerful analyses than are
      employed in most published investigations; hence negative findings should not be
      considered evidence of a lack of effect, and investigations are not hypothesis
      proving unless power calculations show sufficient ability to detect effects.

PMID- 24286209
TI  - Severe congenital factor XIII deficiency caused by novel W187X and G273V
      mutations in the F13A gene; diagnosis and classification according to the
      ISTH/SSC guidelines.
AB  - Factor XIII (FXIII) consists of the A and B subunits (FXIII-A and FXIII-B) and
      stabilizes fibrin clots. Defects in either the FXIII-A or FXIII-B gene lead to
      congenital FXIII deficiency, which manifests a life-long haemorrhagic tendency.
      Thus, prophylactic FXIII replacement therapy is recommended. To establish a
      management plan for a 30-year-old male patient with 'indefinite' FXIII deficiency
      (<40% of the normal FXIII), he was characterized by state-of-the-art techniques
      as guided by the FXIII/Fibrinogen subcommittee of ISTH/SSC. FXIII activity turned
      out to be virtually undetectable by three functional assays. Four immunological
      assays detected essentially no FXIII protein, FXIII-A antigen, and A2 B2 antigen,
      but normal FXIII-B antigen. Accordingly, he was diagnosed as a 'severe' FXIII-A
      deficiency case. He had no anti-FXIII antibodies, because a 1:1 cross-mixing test
      (ammonia release assay) and a five-step mixing test (amine incorporation assay)
      between his plasma and normal plasma demonstrated deficiency patterns.
      Furthermore, a dosing test using plasma-derived FXIII concentrates revealed its
      normal recovery. DNA sequencing analysis identified two novel mutations, W187X &
      G273V, in the F13A gene. Genetic analyses confirmed that he was a compound
      heterozygote and his mother and sister were heterozygotes of either one of these
      mutations, indicating the hereditary nature of this disorder. Molecular modelling
      predicted that the G273V mutation would cause clashes with the surrounding
      residues in the core domain of FXIII-A, and ultimately would result in the
      instability of the mutant molecule. Detailed characterization of 'indefinite'
      FXIII deficiency made it possible to make its definite diagnosis and best
      management plan. 

PMID- 24286210
TI  - The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced
      systemic sclerosis in the mouse.
AB  - INTRODUCTION: The aim of this study was to test the naturally occurring
      organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has
      antibiotic and anticancer properties, as a treatment for HOCl-induced systemic
      sclerosis in the mouse. METHODS: The prooxidative, antiproliferative, and
      cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and
      HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS
      were evaluated in the skin and lungs of HOCl mice. RESULTS: H2O2 production was
      higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P <
      0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS
      dose-dependently increased H2O2 production in HOCl fibroblasts (P < 0.001 with 40
      MUM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl mice, the
      antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were
      significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo,
      DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01)
      and lungs (P < 0.05), alphaSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in
      skin, formation of advanced oxidation protein products and anti-DNA topoisomerase
      1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl
      mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of
      B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes
      stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the
      production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases).
      CONCLUSIONS: The natural organosulfur compound DPTTS prevents skin and lung
      fibrosis in the mouse through the selective killing of diseased fibroblasts and
      its immunomodulating properties. DPTTS may be a potential treatment for systemic
      sclerosis.

PMID- 24286212
TI  - Head-group acylation of monogalactosyldiacylglycerol is a common stress response,
      and the acyl-galactose acyl composition varies with the plant species and applied
      stress.
AB  - Formation of galactose-acylated monogalactosyldiacylglycerols has been shown to
      be induced by leaf homogenization, mechanical wounding, avirulent bacterial
      infection and thawing after snap-freezing. Here, lipidomic analysis using mass
      spectrometry showed that galactose-acylated monogalactosyldiacylglycerols, formed
      in wheat (Triticum aestivum) and tomato (Solanum lycopersicum) leaves upon
      wounding, have acyl-galactose profiles that differ from those of wounded
      Arabidopsis thaliana, indicating that different plant species accumulate
      different acyl-galactose components in response to the same stress. Additionally,
      the composition of the acyl-galactose component of Arabidopsis acMGDG (galactose
      acylated monogalactosyldiacylglycerol) depends on the stress treatment. After sub
      lethal freezing treatment, acMGDG contained mainly non-oxidized fatty acids
      esterified to galactose, whereas mostly oxidized fatty acids accumulated on
      galactose after wounding or bacterial infection. Compositional data are
      consistent with acMGDG being formed in vivo by transacylation with fatty acids
      from digalactosyldiacylglycerols. Oxophytodienoic acid, an oxidized fatty acid,
      was more concentrated on the galactosyl ring of acylated
      monogalactosyldiacylglycerols than in galactolipids in general. Also, oxidized
      fatty acid-containing acylated monogalactosyldiacylglycerols increased
      cumulatively when wounded Arabidopsis leaves were wounded again. These findings
      suggest that, in Arabidopsis, the pool of galactose-acylated
      monogalactosyldiacylglycerols may serve to sequester oxidized fatty acids during
      stress responses. 

PMID- 24286211
TI  - Sphingolipid signalling mediates mitochondrial dysfunctions and reduced
      chronological lifespan in the yeast model of Niemann-Pick type C1.
AB  - The Niemann-Pick type C is a rare metabolic disease with a severe
      neurodegenerative phenotype characterized by an accumulation of high amounts of
      lipids (cholesterol and sphingolipids) in the late endosomal/lysosomal network.
      It is caused by loss-of-function point mutations in either NPC1 or NPC2, which
      seem to mediate proper intracellular lipid transport through endocytic pathway.
      In this study, we show that yeast cells lacking Ncr1p, an orthologue of mammalian
      NPC1, exhibited a higher sensitivity to hydrogen peroxide and a shortened
      chronological lifespan. These phenotypes were associated with increased levels of
      oxidative stress markers, decreased levels of antioxidant defences and
      mitochondrial dysfunctions. Moreover, we report that Ncr1p-deficient cells
      displayed high levels of long chain bases (LCB), and that Sch9p-phospho-T570 and
      Sch9p levels increased in ncr1Delta cells through a mechanism regulated by Pkh1p,
      a LCB-activated protein kinase. Notably, deletion of PKH1 or SCH9 suppressed
      ncr1Delta phenotypes but downregulation of de novo sphingolipid biosynthesis had
      no protective effect, suggesting that LCBs accumulation may result from an
      increased turnover of complex sphingolipids. These results suggest that
      sphingolipid signalling through Pkh1p-Sch9p mediate mitochondrial dysfunction,
      oxidative stress sensitivity and shortened chronological lifespan in the yeast
      model of Niemann-Pick type C disease. 

PMID- 24286213
TI  - Therapeutic potential of midkine in cardiovascular disease.
AB  - Ischaemic heart disease, stroke and their pathological consequences are life
      threatening conditions that account for about half of deaths in developed
      countries. Pathology of these diseases includes cell death due to
      ischaemia/reperfusion injury, vascular stenosis and cardiac remodelling. The
      growth factor midkine plays a pivotal role in these events. Midkine shows an
      acute cytoprotective effect in ischaemia/reperfusion injury at least in part via
      its anti-apoptotic effect. Moreover, while midkine promotes endothelial cell
      proliferation, it also recruits inflammatory cells to lesions. These activities
      eventually enhance angiogenesis, thereby preventing cardiac tissue remodelling.
      However, midkine's activity in recruiting inflammatory cells into the vascular
      wall also triggers neointima formation, and consequently, vascular stenosis.
      Moreover, midkine is induced in cancer tissues where it enhances angiogenesis.
      Therefore, midkine may promote tumour formation through its angiogenic and anti
      apoptotic activity. This review focuses on the roles of midkine in ischaemic
      cardiovascular disease and their pathological consequences, that is angiogenesis,
      vascular stenosis, and cardiac remodelling, and discusses the possible
      therapeutic potential of modulation of midkine in these diseases. LINKED
      ARTICLES: This article is part of a themed section on Midkine. To view the other
      articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24286215
TI  - Surelease or organic solution of ethylcellulose in preparation of sustained
      release theophylline micromatrices or matrices using spray drying technique.
AB  - This study evaluated ethylcellulose (EC) in two forms in preparation of sustained
      release theophylline microparticles using spray drying. Spray dried (SD) samples
      at different drug:polymer ratios were prepared using Surelease (SDaq) or organic
      solutions of ethylcellulose (SDor). Properties of particles (yield, particle
      morphology, size distribution and release profiles) were examined. Differential
      scanning calorimetry (DSC) and infrared spectroscopy (IR) studies were performed
      to track polymorphic changes and/or drug polymer interactions. SD samples were
      compressed and crushing strengths and release profiles were determined. The
      yields were in the range of 55-70%. The SD samples were nearly spherical with
      numerous fine particles attached to their surfaces. The SDor samples showed the
      smallest particle size. No polymorphism or drug-polymer interaction was observed.
      Uncompressed SDaq samples showed inadequate sustained release of drug compared to
      SDor samples. Surelease content did not affect drug release from SDaq samples.
      Tablets prepared from SDaq were softer and showed some plasticity, while those
      prepared from SDor exhibited higher crushing strengths. Tablets prepared from
      SDaq showed sustained release properties while the release of drug from
      compressed SDor samples were too slow. Overall Surelease was unable to sustain
      release of theophylline from SDaq microparticles, however, in compacted form
      showed more appropriate drug release than compacted SDor.

PMID- 24286214
TI  - Independent associations of total and high molecular weight adiponectin with
      cardiometabolic risk and surrogate markers of enhanced early atherogenesis in
      black and white patients with rheumatoid arthritis: a cross-sectional study.
AB  - INTRODUCTION: Whether adiponectin levels associate with atherogenesis in RA is
      uncertain. We examined the independent relationships of total and high molecular
      weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate
      markers of enhanced early atherogenesis in black and white patients with RA.
      METHODS: We determined total and HMW adiponectin concentrations and those of
      endothelial activation molecules including soluble E-selectin, vascular cell
      adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and
      monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA
      patients. Associations were determined in potential confounder and mediator
      adjusted mixed regression models. RESULTS: Total and HMW adiponectin
      concentrations related similarly to metabolic risk factors and endothelial
      activation. In all patients, total and HMW adiponectin concentrations associated
      paradoxically with high systolic, diastolic and mean blood pressure (partial R =
      0.155 to 0.241, P <= 0.03). Ethnic origin did not impact on these relationships
      (interaction P >= 0.09). Total and HMW adiponectin concentrations associated with
      those of glucose in white and black patients respectively (partial R = -0.304, P
      = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW
      adiponectin concentrations also related favorably to lipid profiles (partial R =
      0.292 to 0.360, P <= 0.003 for HDL cholesterol concentrations, -0.269 to -0.299,
      P <= 0.006 for triglyceride concentrations and -0.302 to -0.390, P <= 0.002 for
      total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R
      = -0.210 to -0.238, P <= 0.03). In white but not black patients, total and HMW
      adiponectin concentrations associated paradoxically with overall endothelial
      activation as estimated by a standard z-score of endothelial activation molecule
      concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the
      respective models, the extent of effect of total and HMW adiponectin
      concentrations on endothelial activation was larger in white compared to black
      participants (standardized beta (SE) = 0.260 (0.107) versus -0.106 (0.107), P =
      0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total
      adiponectin ratio related inconsistently to metabolic risk factors and not to
      endothelial activation. CONCLUSION: In this study, total and HMW adiponectin
      concentrations associated with increased blood pressure parameters, and in white
      patients additionally with endothelial activation. The potential mechanism(s)
      underlying these paradoxical relationships between adiponectin concentrations and
      cardiovascular risk in RA merit further investigation.

PMID- 24286216
TI  - Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally
      bioavailable small molecule inhibitor, RO9021, impinges on various innate and
      adaptive immune responses: implications for SYK inhibitors in autoimmune disease
      therapy.
AB  - INTRODUCTION: Spleen tyrosine kinase (SYK) is a key integrator of intracellular
      signals triggered by activated immunoreceptors, including Bcell receptors (BCR)
      and Fc receptors, which are important for the development and function of
      lymphoid cells. Given the clinical efficacy of Bcell depletion in the treatment
      of rheumatoid arthritis and multiple sclerosis, pharmacological modulation of
      Bcells using orally active small molecules that selectively target SYK presents
      an attractive alternative therapeutic strategy. METHODS: A SYK inhibitor was
      developed and assayed in various in vitro systems and in the mouse model of
      collagen-induced arthritis (mCIA). RESULTS: A novel ATP-competitive inhibitor of
      SYK, 6-[(1R,2S)-2-Amino-cyclohexylamino]-4-(5,6-dimethyl-pyridin-2-ylamino)
      pyridazine-3-carboxylic acid amide, designated RO9021, with an adequate kinase
      selectivity profile and oral bioavailability, was developed. In addition to
      suppression of BCR signaling in human peripheral blood mononuclear cells (PBMC)
      and whole blood, FcgammaR signaling in human monocytes, and FcepsilonR signaling
      in human mast cells, RO9021 blocked osteoclastogenesis from mouse bone marrow
      macrophages in vitro. Interestingly, Toll-like Receptor (TLR) 9 signaling in
      human Bcells was inhibited by RO9021, resulting in decreased levels of
      plasmablasts, immunoglobulin (Ig) M and IgG upon B-cell differentiation. RO9021
      also potently inhibited type I interferon production by human plasmacytoid
      dendritic cells (pDC) upon TLR9 activation. This effect is specific to TLR9 as
      RO9021 did not inhibit TLR4- or JAK-STAT-mediated signaling. Finally, oral
      administration of RO9021 inhibited arthritis progression in the mCIA model, with
      observable pharmacokinetics (PK)-pharmacodynamic (PD) correlation. CONCLUSIONS:
      Inhibition of SYK kinase activity impinges on various innate and adaptive immune
      responses. RO9021 could serve as a starting point for the development of
      selective SYK inhibitors for the treatment of inflammation-related and autoimmune
      related disorders.

PMID- 24286217
TI  - Choriodecidual cells from term human pregnancies show distinctive functional
      properties related to the induction of labor.
AB  - PROBLEM: Human parturition is associated with an intrauterine pro-inflammatory
      environment in the choriodecidua. Evidence that some mediators of this signaling
      cascade also elicit responses leading to labor prompted us to characterize the
      cellular sources of these mediators in the human choriodecidua. METHOD OF STUDY:
      Leukocyte-enriched preparations from human choriodecidua (ChL) and intervillous
      placental blood leukocytes (PL) were maintained in culture. Secretions of
      inflammatory cytokines, chemokines, and MMP-9 were documented. Leukocyte
      phenotype of ChL and PL was determined by flow cytometry using specific
      fluorochrome-conjugated antibodies. RESULTS AND CONCLUSIONS: ChL showed a
      distinct pro-inflammatory secretion pattern of cytokines and chemokines when
      compared with PL, including higher amounts of TNF-alpha and IL-6, and decreased
      secretions of IL-4 and IL-1ra. ChL also secreted more MIP-1alpha and MCP-1 and
      MMP-9 than PL. No significant differences were found in leukocytes subsets
      between compartments. Based on our findings, we propose that ChL isolated from
      fetal membranes at term are functionally different from PL and may collaborate to
      modulate the microenvironment linked to induction and progression of human labor.

PMID- 24286218
TI  - Clopidogrel cessation triggers aspirin rebound in patients with coronary stent.
AB  - WHAT IS KNOWN AND OBJECTIVE: Premature discontinuation of clopidogrel in patients
      undergoing percutaneous coronary intervention is a significant risk factor for
      thrombotic adverse outcomes. However, recent studies indicate that even
      discontinuation of long-term use of clopidogrel may be associated with multiple
      adverse outcomes, that is, rebound phenomenon whose mechanism is not definitely
      clear. The aim of the study was to examine the effect of clopidogrel withdrawal
      in those on combined aspirin and clopidogrel therapy. METHODS: This prospective,
      multicenter study enrolled 200 patients who underwent coronary stent implantation
      and were on dual antiplatelet therapy (100 mg aspirin + 75 mg clopidogrel) 1 year
      after the stent placement. In all patients, we measured the platelet aggregation,
      by multiplate electrode aggregometry, using two agonists [adenosine diphosphate
      with PGE1 (ADPHS) and arachidonic acid (ASPI)] two times: on the day of cessation
      of clopidogrel and 90 days after clopidogrel was stopped. RESULTS AND DISCUSSION:
      Following clopidogrel discontinuation, we registered an increase in ASPI values
      (P < 0.001), linear correlation between changes in ASPI and ADPHS values (P =
      0.009) and significant difference in the values of ASPI first quartile of ADPHS
      compared with the other three (P < 0.001, P = 0.016, P < 0.001, I vs. II, I vs.
      III and I vs. IV quartile of ADPHS, respectively). WHAT IS NEW AND CONCLUSION:
      Our findings show that cessation of clopidogrel causes loss of antiplatelet
      synergism with aspirin, leading to a weakening of the response to aspirin, which
      may be one explanation for the rebound after the clopidogrel cessation.

PMID- 24286219
TI  - Impact of epicardial ablation of concomitant atrial fibrillation on atrial
      natriuretic peptide levels and atrial function in 6 months follow-up: does
      preoperative ANP level predict outcome of ablation?
AB  - BACKGROUND: Epicardial ablation concomitant to cardiac surgery is an easy and
      safe approach to treat atrial fibrillation (AF), but its efficacy in longstanding
      persistent (LsPe) AF remains intermediate. Although larger left atrial size has
      been associated with worse outcome after ablation, biochemical predictors of
      success are not well established. The aim of this study was to evaluate
      relationship between biochemical marker, echo-characteristic and cardiac rhythm
      in 6 months follow-up after epicardial ultrasound (HIFU) ablation. METHODS: We
      included 78 consecutive patients, who underwent elective cardiac surgery. 42
      patients with AF (11.9% paroxysmal, 23.8% persistent, 64.3% LsPeAF) underwent
      concomitant HIFU ablation (AF ablation group), 16 with AF underwent cardiac
      surgery without ablation (AF control) and 20 had preoperatively normal sinus
      rhythm (SR control). We measured plasma ANP secretion before, on postoperative
      day (POD) 1, POD 7 as well as 3 and 6 months after surgery. Moreover, we
      estimated cardiac rhythm and atrial mechanical function by Atrial Filling
      Fraction (AFF) and A-wave velocity in follow-up. RESULTS: Baseline ANP levels
      were higher in patients with LsPeAF, as compared to the paroxysmal and permanent
      AF and to the SR control group. Patients with LsPeAF (n = 27) who converted to SR
      had preoperatively smaller left atrial diameter (LAD) and LA area (p < 0.05) and
      higher ANP level (p = 0.009) than those who remained in AF at 6 months after
      ablation. Multivariate regression analysis revealed that only preoperative ANP
      level was an independent predictor of cardiac rhythm after ablation. Patients
      with LsPeAF and preoperative ANP >7.5 nmol/l presented with SR in 80%, in
      contrast to those with ANP <7.5 nmol/l who converted to SR in 20%. We detected
      gradual increase of AFF and A-velocity at 6 months after ablation (p < 0.05)
      solely in AF ablation group. ANP levels were increased on POD 1 in ablation group
      (p < 0.05), without changes in further follow-up. CONCLUSION: Our results
      indicate that preoperative ANP levels may be a new biochemical predictor of
      successful epicardial ablation in patients with concomitant LsPeAF. HIFU ablation
      caused a significant improvement of atrial mechanical function and gradual
      increase of AFF and did not associate with alteration of atrial endocrine
      secretion at 6 months follow-up.

PMID- 24286220
TI  - Interleukin-17A- or tumor necrosis factor alpha-mediated increase in
      proliferation of T cells cocultured with synovium-derived mesenchymal stem cells
      in rheumatoid arthritis.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) represent promising applications in
      rheumatoid arthritis (RA). However, the inflammatory niche in the RA synovium
      could adversely affect MSC function. This study was designed to investigate
      biologic and immunologic properties of synovium-derived MSCs (SMSCs) in RA, with
      particular focus on whether cytokines can mediate increase of proliferation of T
      cells cocultured with SMSCs in RA. METHODS: Compared with SMSCs from eight
      healthy donors (HDs), SMSCs from 22 patients with RA (RAp) were evaluated. The
      methyl thiazolyl tetrazolium (MTT) assay was used to assess cell-population
      doubling and viability. Multipotentiality of SMSCs was examined by using
      appropriate culture conditions. Flow cytometry was used to investigate the marker
      phenotype of SMSCs. Immunomodulation potential of SMSCs was examined by mixed
      peripheral blood mononuclear cells (PBMCs) reactions, and then by PBMCs or
      synovial T cells with or without the addition of inflammatory cytokines
      (interleukin-17A (IL-17A), tumor necrosis factor-alpha (TNF-alpha), and
      interferon-gamma (IFN-gamma)) after stimulation with phytohemagglutinin (PHA),
      respectively. RESULTS: SMSCs from RA patients (RA-SMSCs) showed normal population
      doubling, cell viability, multiple differentiation characteristics, and surface
      markers. In either mixed PBMC reactions or PBMC proliferation stimulated with
      PHA, RA-SMSCs showed normal immunomodulation function compared with SMSCs from
      healthy donors (HD-SMSCs). However, the increase in proliferation of T cells was
      observed when IL-17A and TNF-alpha were added alone or in combination.
      CONCLUSIONS: Our data suggest that the inflammatory niche, especially these
      cytokines, may increase the proliferation of T cells cocultured with SMSCs in RA.

PMID- 24286221
TI  - Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans.
AB  - NDG-4 is a predicted transmembrane acyltransferase protein that acts in the
      distribution of lipophilic factors. Consequently, ndg-4 mutants lay eggs with a
      pale appearance due to lack of yolk, and they are resistant to sterility caused
      by dietary supplementation with the long-chain omega-6 polyunsaturated fatty acid
      dihommogamma-linolenic acid (DGLA). Two other proteins, NRF-5 and NRF-6, a
      homolog of a mammalian secreted lipid binding protein and a NDG-4 homolog,
      respectively, have previously been shown to function in the same lipid transport
      pathway. Here, we report that mutation of the NDG-4 protein results in increased
      organismal stress resistance and lifespan. When NDG-4 function and insulin/IGF-1
      signaling are reduced simultaneously, maximum lifespan is increased almost
      fivefold. Thus, longevity conferred by mutation of ndg-4 is partially overlapping
      with insulin signaling. The nuclear hormone receptor NHR-80 (HNF4 homolog) is
      required for longevity in germline less animals. We find that NHR-80 is also
      required for longevity of ndg-4 mutants. Moreover, we find that nrf-5 and nrf-6
      mutants also have extended lifespan and increased stress resistance, suggesting
      that altered lipid transport and metabolism play key roles in determining
      lifespan. 

PMID- 24286222
TI  - Good versus poor therapeutic alliances with non-accepting parents of same-sex
      oriented adolescents and young adults: a qualitative study.
AB  - OBJECTIVE: Therapeutic themes and processes associated with five good versus five
      poor parent-therapist alliances among a sample of non-accepting parents of sexual
      minority youth/young adults participating in family therapy were examined.
      METHOD: The Consensual Qualitative Research approach was used to analyse of
      therapy notes and follow-up interviewsfrom good and poor alliances. RESULTS: In
      good alliances, parents adopted relationship building as a goal, considered
      essentialist causal attributions of same-sex orientation, acknowledged positive
      aspects of their child, and perceived the therapist as empathic and accepting.
      Parents with poor alliances rejected relationship building as a goal, rebuffed
      essentialist causal attributions, dismissed the possibility of their own coming
      out, nullified positive aspects of their child, sought to change their child's
      sexual orientation, blamed therapists for validating their child's same-sex
      orientation, and pressured therapists for information about their child.
      CONCLUSIONS: Clinical implications are discussed.

PMID- 24286223
TI  - Ethyl glyoxylate N-tosylhydrazone as sulfonyl-transfer reagent in base-catalyzed
      sulfa-Michael reactions.
AB  - Ethyl glyoxylate N-tosylhydrazone has been identified as an excellent sulfonyl
      anion surrogate in the DBU-catalyzed conjugate addition reaction with enones and
      enals for the synthesis of functionalized sulfones. The reaction proceeds under
      base-catalyzed conditions and provides a direct access to gamma-keto- and gamma
      hydroxy sulfones in a simple and reliable way through a sulfa-Michael reaction
      that proceeds with high yield and chemoselectivity. 

PMID- 24286224
TI  - Structural determinants of the hydrogen peroxide permeability of aquaporins.
AB  - Aquaporins (AQP) conduct small, uncharged molecules, such as water (orthodox
      AQPs), ammonia (aquaammoniaporins) or glycerol (aquaglyceroporins). The
      physiological functions of AQPs are involved in osmotic volume regulation or the
      transport of biochemical precursors and metabolic waste products. The recent
      identification of hydrogen peroxide (H2O2) as a permeant of certain AQPs suggests
      additional roles in mitigating oxidative stress or enabling paracrine H2O2
      signalling. Yet, an analysis of the structural requirements of the H2O2
      permeability of AQPs is missing. We subjected a representative set of wild-type
      and mutant AQPs to a newly established quantitative phenotypic assay. We
      confirmed high H2O2 permeability of the human aquaammoniaporin AQP8 and found
      intermediate H2O2 permeability of the prototypical orthodox water channel AQP1
      from the rat. Differences from an earlier report showing an absence of H2O2
      permeability of human AQP1 can be explained by expression levels. By generating
      point mutations in the selectivity filter of rat orthodox aquaporin AQP1, we
      established a correlation of H2O2 permeability primarily with water permeability
      and secondarily with the pore diameter. Even the narrowest pore of the test set
      (i.e. rat orthodox aquaporin AQP1 H180F with a pore diameter smaller than that of
      natural orthodox AQPs) conducted water and H2O2. We further found that H2O2
      permeability of the aquaglyceroporin from the malaria parasite Plasmodium
      falciparum was lower despite its wider pore diameter. The data suggest that all
      water-permeable AQPs are H2O2 channels, yet H2O2 permeability varies with the
      isoform. Thus, generally, AQPs must be considered as putative players in
      situations of oxidative stress (e.g. in Plasmodium-infected red blood cells,
      immune cells, the cardiovascular system or cells expressing AQP8 in their
      mitochondria).

PMID- 24286225
TI  - The importance of the therapeutic relationship in improving the patient's
      experience in the in-patient setting.

PMID- 24286226
TI  - Lack of seasonal variation in bleeding and patient-assessed pain patterns in
      patients with haemophilia B receiving on-demand therapy.
AB  - Spontaneous haemorrhage in patients with haemophilia is generally considered to
      occur randomly and without a predictable temporal or seasonal pattern; however,
      there is a lack of evidence in the literature on the effects of weather,
      temperature and atmosphere on bleeding episodes. This post hoc analysis of a
      multicentre, open-label crossover study examined the influence of seasonality on
      bleeding frequency and patient-assessed pain in patients with moderately severe
      and severe (FIX C <= 2%) haemophilia B. Fifty patients were enrolled and treated
      on-demand for 16 weeks; 47 were subsequently randomized to one of two
      prophylactic regimens (nonacog alfa 100 IU kg(-1) once weekly or 50 IU kg(-1)
      twice weekly) for 16 weeks. Patients then underwent an 8-week washout period of
      on-demand therapy before being crossed over to the other prophylactic regimen for
      16 weeks. Bleeding episodes during the on-demand treatment periods were analysed.
      To assess for temporal trends, data were graphed as scatter plots. The primary
      end point was the annualized bleeding rate (ABR). Additional measures included
      raw and median pain scores during every joint bleeding event (spontaneous or
      traumatic), with pain scored using the Brief Pain Inventory (0 = 'no pain' to 10
      = 'pain as bad as you can imagine'). The observed ABRs during the on-demand
      periods showed no distinguishable trend over time. Analysis of pain associated
      with joint bleeding episodes also did not demonstrate any discernible temporal
      trend. No apparent seasonal variation in bleeding pattern or patient-reported
      pain was observed in this analysis of patients with haemophilia B. 

PMID- 24286228
TI  - 5-HT2A receptor antagonists for the treatment of neuroleptic-induced akathisia: a
      systematic review and meta-analysis.
AB  - Akathisia is a common and distressing extrapyramidal side-effect, which usually
      results from the use of antipsychotic medication. Previous reviews and meta
      analyses have demonstrated a lack of evidence for the effectiveness of treatment
      strategies, which are traditionally used against neuroleptic-induced akathisia
      (NIA), i.e. beta-blockers, anticholinergic agents and benzodiazepines. In the
      last fifteen years, randomized trials have studied the effect of drugs with
      antiserotonergic properties on NIA. We conducted a systematic review of
      randomized control trials and used meta-analytic methods to quantify the overall
      effect size. PubMed and the Cochrane libraries were searched for eligible trials.
      Six randomized controlled trials were found, five of which included a placebo
      control group and qualified for our meta-analysis. The overall effect size in the
      analysis is RR = 7.10 with 95% CI 3.08-16.40 (p < 0.0001). Our findings suggest
      that 5-HT(2A) antagonists are effective in the treatment of NIA.

PMID- 24286229
TI  - Auxin gradients across wood-instructive or incidental?
AB  - Various aspects of wood formation have been linked to the action of auxin, e.g.
      cambial activity, dormancy, secondary cell wall deposition and tension wood
      formation. The presence of a radial auxin concentration gradient across wood
      forming tissue has been suggested to regulate cambial activity and
      differentiation of cambial derivatives by providing positional information to
      cells within the tissue. Similar patterning mechanisms that depend on the
      interpretation of auxin thresholds have subsequently been proposed for shoot and
      root apical meristems. However, direct evidence for the existence of auxin
      gradients has only been obtained for the cambium of various tree species. While
      the auxin gradient theory is based on a plethora of descriptive and
      pharmacological experiments, in recent years, auxin function on wood formation
      has been underpinned by molecular and functional data. Here, we review the latest
      progress in understanding the role of auxin in wood formation and discuss how
      auxin concentration gradients could be established and interpreted in wood
      forming tissues. 

PMID- 24286230
TI  - A study of the DNA damage checkpoint in Candida albicans: uncoupling of the
      functions of Rad53 in DNA repair, cell cycle regulation and genotoxic stress
      induced polarized growth.
AB  - In response to genotoxic stress (GS), Candida albicans can undergo polarized
      growth and massive genome rearrangements including loss-of-heterozygosity (LOH)
      events. We evaluated the contribution of the CaRad53p and CaDun1p kinases of the
      DNA damage checkpoint (DDCP) in these processes. Characterization of C. albicans
      rad53DeltaDelta and dun1DeltaDelta mutants revealed that the two kinases were
      involved in the maintenance of heterozygosity. SNP-RFLP typing and whole-genome
      sequencing of rad53DeltaDelta isolates having undergone a LOH revealed that,
      according to the chromosome on which LOH had occurred, these were predominantly
      due to break-induced replication/mitotic cross-over or chromosome loss. Loss of
      CaRAD53 also resulted in frequent aneuploidies. Deletion of CaDUN1 led to an
      increase in recombination-dependent LOH but did not trigger aneuploidies. It also
      increased GS sensitivity but did not impair GS-induced polarized growth contrary
      to CaRAD53 deletion. Characterization of CaRad53p site-directed mutants
      demonstrated that its kinase activity and N-terminal phosphorylation sites were
      crucial for its function in the resistance to GS, maintenance of heterozygosity,
      cell cycle regulation and polarized growth. Moreover, using phosphomimic mutants,
      we revealed an uncoupling of the functions of CaRad53p in these different
      processes, thus providing a novel understanding of how the DDCP may regulate
      downstream events in response to GS. 

PMID- 24286227
TI  - Transient receptor potential (TRP) channels in the airway: role in airway
      disease.
AB  - Over the last few decades, there has been an explosion of scientific publications
      reporting the many and varied roles of transient receptor potential (TRP) ion
      channels in physiological and pathological systems throughout the body. The aim
      of this review is to summarize the existing literature on the role of TRP
      channels in the lungs and discuss what is known about their function under normal
      and diseased conditions. The review will focus mainly on the pathogenesis and
      symptoms of asthma and chronic obstructive pulmonary disease and the role of four
      members of the TRP family: TRPA1, TRPV1, TRPV4 and TRPM8. We hope that the
      article will help the reader understand the role of TRP channels in the normal
      airway and how their function may be changed in the context of respiratory
      disease. 

PMID- 24286231
TI  - Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological
      malignancies and febrile neutropenia after chemotherapy.
AB  - INTRODUCTION: Patients with febrile neutropenia (FN) exhibit changes in
      extracellular fluid that may alter the plasma concentrations of beta-lactams and
      result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of
      piperacillin/tazobactam in patients with hematological malignancies and FN after
      receiving chemotherapy at a primary public cancer center. METHODS: This was an
      open, nonrandomized, observational, descriptive, and prospective study. Samples
      from 15 patients with hematological malignancies and FN were evaluated after the
      administration of chemotherapy. Five blood samples were taken from each patient
      when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after
      each dose. Antibiotic concentrations were measured using gel diffusion with
      Bacillus subtilis. All study participants provided written informed consent.
      RESULTS: We investigated the pharmacokinetics of piperacillin in 14 patients
      between the ages of 18 years and 59 years and with a mean absolute neutrophil
      count of 208 cells per mm3 (standard deviation (SD) +/- 603.2). The following
      pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133
      mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65
      L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h);
      half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12
      827.16 mg . h/L. CONCLUSION: Patients with FN after receiving chemotherapy
      exhibited significant variations in the pharmacokinetic parameters of
      piperacillin compared with healthy individuals; specifically, FN patients
      demonstrated an increase in t1(/2) and decreased CL.

PMID- 24286233
TI  - The cognitive process of identity reconstruction after the onset of a
      neurological disability.
AB  - PURPOSE: Rehabilitation professionals and researchers underscore the impact of an
      acquired disability on identity. However, the cognitive process by which identity
      is transformed is understudied. The present study aims to explore the cognitive
      process by which personal identity is reconstructed following disability onset.
      METHODS: A template organizing style of interpretation was used to perform a
      qualitative analysis based on the Cognitive-Developmental Model of Social
      Identity Integration (CDMSII) using interview data from 10 participants with
      traumatic brain injury or traumatic spinal cord injury. RESULTS: As suggested by
      the CDMSII, following the accident, participants initially tend to emphasize
      distinctions between their pre- and post-injury conditions. Eventually,
      individuals are able to create cognitive connections between pre-injury self
      knowledge and how they understand their new condition. Finally, in the last stage
      of the identity integration process, the various identity components are
      recognized as part of the self. Organizing data based on the three stages of this
      theory was found to resonate with participants and aided the comprehension of how
      every stage in the identity reconstruction process is intertwined with the need
      for continuity through life. CONCLUSIONS: The CDMSII offers a useful heuristic
      for understanding long-term identity reconstruction and the present research
      emphasizes the importance of a sense of continuity following disability onset.

PMID- 24286232
TI  - Partial inhibition and bilevel optimization in flux balance analysis.
AB  - MOTIVATION: Within Flux Balance Analysis, the investigation of complex subtasks,
      such as finding the optimal perturbation of the network or finding an optimal
      combination of drugs, often requires to set up a bilevel optimization problem. In
      order to keep the linearity and convexity of these nested optimization problems,
      an ON/OFF description of the effect of the perturbation (i.e. Boolean variable)
      is normally used. This restriction may not be realistic when one wants, for
      instance, to describe the partial inhibition of a reaction induced by a drug.
      RESULTS: In this paper we present a formulation of the bilevel optimization which
      overcomes the oversimplified ON/OFF modeling while preserving the linear nature
      of the problem. A case study is considered: the search of the best multi-drug
      treatment which modulates an objective reaction and has the minimal perturbation
      on the whole network. The drug inhibition is described and modulated through a
      convex combination of a fixed number of Boolean variables. The results obtained
      from the application of the algorithm to the core metabolism of E.coli highlight
      the possibility of finding a broader spectrum of drug combinations compared to a
      simple ON/OFF modeling. CONCLUSIONS: The method we have presented is capable of
      treating partial inhibition inside a bilevel optimization, without loosing the
      linearity property, and with reasonable computational performances also on large
      metabolic networks. The more fine-graded representation of the perturbation
      allows to enlarge the repertoire of synergistic combination of drugs for tasks
      such as selective perturbation of cellular metabolism. This may encourage the use
      of the approach also for other cases in which a more realistic modeling is
      required.

PMID- 24286234
TI  - Talking about sex after traumatic brain injury: perceptions and experiences of
      multidisciplinary rehabilitation professionals.
AB  - PURPOSE: Research indicates that although 50-60% of people who have had a
      traumatic brain injury (TBI) experience changes in sexual functioning, sexuality
      issues remain largely unaddressed in rehabilitation. This study aimed to explore
      rehabilitation professionals' perceptions and experiences of discussing sexuality
      with service-users who have had a TBI. METHOD: Purposeful sampling was used to
      recruit 24 participants from two local National Health Service trusts and from a
      national charity. Four focus groups were conducted with pre-existing groups of
      professionals, using a semi-structured interview schedule. Focus group data were
      transcribed verbatim and analysed using thematic analysis. RESULTS: Six main
      themes were derived from the analysis: (1) sexuality after TBI is a specialist
      issue; (2) sexuality is a sensitive subject; (3) practicalities of discussing
      sexuality; (4) roles and responsibilities; (5) dilemmas about risk and
      vulnerabilities; and (6) organisational and structural issues. CONCLUSIONS: Our
      findings suggest that a more proactive approach to addressing sexuality issues be
      taken by incorporating sexuality into assessments and by having sexuality
      information available for service-users. Support for professionals is also needed
      in the form of the development of policy, on-going training and supervision.
      Implications for Rehabilitation Rehabilitation professionals find it difficult to
      deal with issues of sexuality following TBI, and the reasons for this are complex
      and interrelated. To provide holistic care, a more proactive approach to
      addressing sexuality issues should be taken. Professionals do not need to be an
      expert in sexual issues to open dialogue. Sexuality discussions should be
      incorporated into assessments, and written information should be available for
      service-users. Further training for professionals and organisational policy
      change is sometimes required to effectively deal with sexuality issues.

PMID- 24286236
TI  - Uterine myomas treated with microwave ablation: the agreement between ablation
      volumes obtained from contrast-enhanced sonography and enhanced MRI.
AB  - PURPOSE: This study explores the agreement between ablated uterine myoma volumes
      obtained from contrast-enhanced sonography and enhanced magnetic resonance
      imaging (MRI) after microwave ablation therapy. MATERIALS AND METHODS: Twenty
      uterine myomas in 18 patients (average size: 5.56 +/- 1.26 cm) were successfully
      treated by microwave ablation. Contrast-enhanced sonography and enhanced MRI were
      performed within 7 days after the treatment. The ablation range of uterine myomas
      was observed and the ablation volume was calculated. By using the intraclass
      correlation coefficient (ICC) and Bland-Altman regression analysis, the agreement
      between ablated uterine myoma volumes obtained from contrast-enhanced sonography
      and enhanced MRI after microwave ablation therapy was analysed. RESULTS: The
      ablated volume ranged from 13.66 to 135.27 cm(3) after ablation, and the mean
      volume was 66.59 +/- 35.71 cm(3) by using contrast-enhanced sonography.
      Respectively, the ablated volume ranged from 10.88 to 137.83 cm(3), and the mean
      volume was 66.81 +/- 35.45 cm(3) by using enhanced MRI. The limits of agreement
      between the two methods were (-10.83 cm(3), 8.39 cm(3)), ICC was 0.991 (F =
      209.61, P < 0.05), and 95% confidence interval is (0.976, 0.996). The results
      revealed a good agreement between the two examination methods of contrast
      enhanced sonography and enhanced MRI. CONCLUSIONS: Contrast-enhanced sonography
      and enhanced MRI can be used interchangeably in observing the ablation range of
      uterine myomas treated with microwave ablation. Contrast-enhanced sonography can
      be used as a preferred non-invasive examination and for follow-up. Meanwhile,
      enhanced MRI can be used to comprehensively determine the relationships among
      uterine myomas, the entire uterus, and surrounding tissues.

PMID- 24286235
TI  - The effects of staged intra-articular injection of cultured autologous
      mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in
      caprine model.
AB  - INTRODUCTION: Treatment of chondral injuries remains a major issue despite the
      many advances made in cartilage repair techniques. Although it has been
      postulated that the use of marrow stimulation in combination with cell-based
      therapy may provide superior outcome, this has yet to be demonstrated. A pilot
      study was thus conducted to determine if bone marrow derived mesenchymal stromal
      cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow
      stimulation (BMS) techniques. METHODS: Two full-thickness chondral 5 mm diameter
      defects were created in tandem on the medial condyle of left stifle joints of 18
      Boer caprine (N = 18). Goats were then divided equally into three groups.
      Simultaneously, bone marrow aspirates were taken from the iliac crests from the
      goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six
      weeks later, BMS surgery, which involves subchondral drilling at the defect
      sites, was performed. After two weeks, the knees in Group 1 were given autologous
      intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there
      were no supplementations provided. In Group 3, no intervention was administered.
      The caprines were sacrificed after six months. Repairs were evaluated using
      macroscopic assessment through the International Cartilage Repair Society (ICRS)
      scoring, histologic grading by O'Driscoll score, biochemical assays for
      glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and
      Sox9. RESULTS: Histological and immunohistochemical analyses demonstrated hyaline
      like cartilage regeneration in the transplanted sites particularly in Group 1. In
      contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The
      highest ICRS and O'Driscoll scorings was also observed in Group 1, while the
      lowest score was seen in Group 3. Similarly, the total GAG/total protein as well
      as chondrogenic gene levels were expressed in the same order, that is highest in
      Group 1 while the lowest in Group three. Significant differences between these 3
      groups were observed (P <0.05). CONCLUSIONS: This study suggests that
      supplementing intra-articular injections of BM-MSCs following BMS knee surgery
      provides superior cartilage repair outcomes.

PMID- 24286237
TI  - Genetic variation in the monoamine oxidase A and serotonin transporter genes in
      sudden infant death syndrome.
AB  - AIM: The purpose of this study was to investigate common polymorphisms in the
      genes encoding monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) in
      Norwegian cases of sudden infant death syndrome (SIDS). This was done to further
      elucidate the role of genetic variation in these genes and SIDS. METHODS: A
      variable number of tandem repeat area in the promoter of the MAOA gene and
      rs25531 in the promoter region of the gene encoding 5-HTT were investigated in
      193 SIDS cases and 335 controls. The methods used were polymerase chain reaction,
      restriction fragment analysis and gel electrophoresis. RESULTS: There were no
      differences between SIDS cases and controls for any of the investigated
      polymorphisms. This was also true when male and female SIDS cases were analysed
      separately. CONCLUSION: This article indicates that neither the VNTR in the
      promoter of the MAOA gene, nor rs25531 in the gene encoding 5-HTT, is involved in
      SIDS. However, as medullary serotonergic abnormalities most likely contribute to
      the death in at least some SIDS cases, it is important to investigate these
      genes, as well as other genes involved in the serotonergic network, in more
      detail.

PMID- 24286238
TI  - SLIT3 is increased in supracervical human foetal membranes and in labouring
      myometrium and regulates pro-inflammatory mediators.
AB  - PROBLEM: Inflammation is associated with preterm birth, a worldwide healthcare
      issue. SLIT3 has a role in inflammation, and thus, the purpose of this study was
      to determine the effect of SLIT3 on labour mediators in human gestational
      tissues. METHOD OF STUDY: SLIT3 protein expression was performed using
      immunohistochemistry in foetal membranes and myometrium with no labour and after
      labour. Foetal membranes were also obtained from a distal site (DS) and
      supracervical site (overlying the cervix; SCS). SLIT3 gene silencing was achieved
      using siRNA in primary amnion and myometrial cells. Pro-inflammatory and pro
      labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography.
      RESULTS: SLIT3 expression was greater in foetal membranes from the SCS compared
      with DS and in myometrium after term spontaneous labour onset. SLIT3 siRNA in
      primary amnion and myometrial cells decreased IL-1beta-induced pro-inflammatory
      cytokine gene expression and release (IL-6 and IL-8) and MMP-9 gene expression
      and release. In amnion cells, SLIT3 siRNA knockdown decreased IL-1beta-induced
      COX-2 expression and prostaglandin PGE2 release. There was no effect of SLIT3
      siRNA on IL-1beta-induced NF-kappaB transcriptional activity. CONCLUSION: Our
      results demonstrate that SLIT3 is increased with labour, and both our amnion and
      our myometrial studies describe a pro-inflammatory effect of SLIT3 in these
      tissues.

PMID- 24286239
TI  - Sex differences in the treatment and outcome of patients with acute coronary
      syndrome after percutaneous coronary intervention: a population-based study.
AB  - BACKGROUND: This study was performed to assess the influence of sex on drug
      therapy and long-term outcomes in acute coronary syndrome (ACS) patients who
      underwent percutaneous coronary intervention (PCI). METHODS: This is a
      retrospective cohort study of ACS patients who underwent PCI [women (n=8,884) and
      men (n=23,937)] between January 1, 2006, and December 31, 2007, with at least a 1
      year follow-up, based on the National Health Insurance Research Database in
      Taiwan. Propensity score was used to identify a 1:1 matched cohort (n=17,768) for
      multivariable adjustment. The influence of sex on drug therapy and outcomes was
      examined by multivariate logistic regression and multivariable Cox proportional
      hazards regression. RESULTS: Female patients had an 18% and 12% lower likelihood
      of receiving aspirin (adjusted odds ratio [OR(adj)]=0.82, 95% confidence interval
      [CI]=0.77-0.88) and clopidogrel (OR(adj)=0.88, 95% CI=0.81-0.95), respectively,
      than male patients but had a 17% and 22% higher likelihood of receiving beta
      blockers (OR(adj)=1.17, 95% CI=1.10-1.24) and statins (OR(adj)=1.22, 95% CI=1.14
      1.29), respectively, than male patients in the matched cohort. The adjusted
      hazard ratio (HR(adj)) of rehospitalization for revascularization in women was
      0.84 (95% CI=0.79-0.90) compared with men after at least a 1-year follow-up in
      the matched cohort. CONCLUSIONS: Female patients with ACS who underwent PCI were
      less likely to receive aspirin and clopidogrel but were more likely to receive
      beta-blockers and statins than male patients. Male sex was associated with a
      higher risk of rehospitalization for revascularization than female sex.

PMID- 24286240
TI  - Abdominal obesity is associated with albuminuria in women: the 2011 Korea
      National Health and Nutrition Examination Survey.
AB  - BACKGROUND: The effects of obesity on the kidney, apart from diabetes or
      hypertension, have not drawn much attention. Moreover, only a few studies have
      reported the relationship between obesity status and albuminuria in Asian
      countries, including South Korea. Therefore, this study aimed to investigate the
      association between obesity status and albuminuria in Korean adults. METHODS: We
      analyzed data from the 2011 Korea National Health and Nutrition Examination
      Survey. Of the 4,979 subjects included in the general-population group, 3,274
      were sorted into a nondiabetic and nonhypertensive population group. Obesity
      status was measured by body mass index and waist circumference. Albuminuria was
      defined as a urine albumin-to-creatinine ratio >=30 mg/g. RESULTS: Abdominally
      obese women were at higher risk for albuminuria than were women without abdominal
      obesity both in the general population (odds ratio [OR], 95% confidence interval
      [CI]: 2.08 [1.04-4.16]) and in the nondiabetic and nonhypertensive population (OR
      [95% CI]: 6.96 [2.34-20.64]) after further adjustment for confounders. Among
      generally nonobese women, abdominally obese women were at higher risk for
      albuminuria than were women without abdominal obesity both in the general
      population (OR [95% CI]: 2.82 [1.51-5.29]) and in the nondiabetic and
      nonhypertensive population (OR [95% CI]: 5.32 [1.47-19.22]). CONCLUSION:
      Abdominal obesity is associated with an increased risk for albuminuria in Korean
      women, independently of diabetes or hypertension. Screening for abdominal
      obesity, especially in women, may therefore provide earlier identification of
      individuals at risk for developing renal disease and cardiovascular disease, even
      those who are nondiabetic and nonhypertensive.

PMID- 24286241
TI  - Medical-grade collagen peptide in injectables provides antioxidant protection.
AB  - Medical-grade collagen peptide is used as an additive agent in pharmaceutical
      formulations; however, it is unknown as to whether the compound exerts
      antioxidant effects in vitro. In this study, we evaluated the antioxidant effects
      of medical-grade collagen peptide on reactive oxygen species such as hydroxyl
      radical, superoxide anion radical and singlet oxygen using electron spin
      resonance and spin trapping. We confirmed that medical-grade collagen peptide
      directly inhibited hydroxyl radical generated by the Fenton reaction or by
      ultraviolet irradiation of hydrogen peroxide, and singlet oxygen. In addition, an
      antioxidant effect of medical-grade collagen peptide on singlet oxygen was
      observed in peptide fractions 12-22. The total amount of antioxidant amino acids
      (Gly, Hyp, Glu, Ala, Cys, Met and His) constituted more than half of the total
      amino acids in these fractions. These results suggest that the observed
      antioxidant properties of medical-grade collagen peptide are due to the compound
      containing antioxidant amino acids. Medical-grade collagen peptide, which is used
      in pharmaceuticals, and especially in injectables, could provide useful
      antioxidant properties to protect the active ingredient from oxidation.

PMID- 24286242
TI  - IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the
      synovial fibroblasts from rheumatoid arthritis patients.
AB  - INTRODUCTION: We previously reported that IL-29, a newly described member of
      interferon (IFN) family, was overexpressed in blood and synovium of rheumatoid
      arthritis (RA) patients and triggered proinflammatory cytokine IL-6 and IL-8 mRNA
      expression in RA synovial fibroblasts (RA-FLS). This suggests that IL-29 has an
      important role in synovial inflammation. Toll-like receptors (TLRs) also activate
      RA-FLS to produce inflammatory mediators including tumor necrosis factor alpha
      (TNF-alpha) and IL-1beta in RA-FLS. Since the TLR family plays an early role in
      the innate immune response and the subsequent induction of the adaptive immune
      response, we hypothesize that IL-29 interacts with TLRs in RA inflammation. This
      study aimed to investigate the effect of IL-29 on TLR-mediated proinflammatory
      cytokine production in RA-FLS. METHODS: The mRNA level of IL-29 receptors (IL
      28Ralpha and IL-10R2) in RA-FLS was determined by semi-quantitative RT- PCR. IL-6
      and IL-8 mRNA expressions in RA-FLS were evaluated by real-time PCR after pre
      incubation with IL-29 and subsequent stimulation with peptidoglycan (PGN, TLR2
      ligand), or polycytidylic acid (poly(I:C), TLR3 ligand), or lipopolysaccharide
      (LPS, TLR4 ligand) . The production of TLR2, 3, and 4 in RA-FLS after IL-29
      stimulation was also assessed by real-time PCR and flow cytometry. IL-29 mRNA and
      protein expression in RA-FLS after stimulation with PGN, poly(I:C), or LPS were
      measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA),
      respectively. RESULTS: The IL-29 receptor complex (IL-28Ralpha and IL-10R2) was
      identified in RA-FLS. IL-29 enhanced TLR-mediated IL-6 and IL-8 expression in RA
      FLS. IL-29 upregulated expression of TLR2, 3 and 4 in RA-FLS. Exposure to PGN,
      poly(I:C) or LPS triggered IL-29 production by RA-FLS. CONCLUSIONS: We show for
      the first time that IL-29 enhances TLR-induced proinflammatory cytokine
      production in RA-FLS via upregulation of TLRs.

PMID- 24286243
TI  - Repeated autologous intraarticular blood injections as an animal model for joint
      pain in haemophilic arthropathy.
AB  - INTRODUCTION: Haemophilic arthropathy following recurrent joint bleedings is one
      of the major disease-related complications in people with haemophilia (PWH),
      leading to mostly chronic joint pain. Since many antinociceptive principles
      interfere with the clotting system, PWH are restricted in treatment options,
      thereby defining a medical need for novel therapeutic principles. However, we
      lack the availability of an animal model for joint pain in haemophilic
      arthropathy for testing these. METHODS: In this study, we aimed to validate the
      rat model of repeated autologous intraarticular blood injections specifically for
      pain-related behavior. During an observation period of 50 days, groups of animals
      were injected weekly into one knee joint with either whole blood or
      cellular/plasma components. RESULTS: Injections induced primary hyperalgesia
      starting after the third injection, accompanied by mild functional gait changes
      and joint swelling. Secondary hyperalgesia and quantitative gait disturbances
      were not observed. This phenotype was most prominent in whole blood injected
      animals, with effect sizes of cells and plasma being additive. In order to
      differentiate haemophilia-related arthropathy from traumatic joint bleeding,
      another group was injected with whole blood only once, which did not cause any
      alterations. CONCLUSIONS: Repeated autologous intraarticular injections of blood
      showed a time course, inflammatory response and reduction in pain thresholds
      similar to the signs and symptoms observed in PWH. Therefore, this model may be
      utilised in the future for testing novel antinociceptive principles in
      haemophilia-associated joint pain.

PMID- 24286244
TI  - Bioethanol production from rice straw by popping pretreatment.
AB  - BACKGROUND: Rice straw has considerable potential as a raw material for
      bioethanol production. Popping pretreatment of rice straw prior to downstream
      enzymatic hydrolysis and fermentation was found to increase cellulose to glucose
      conversion efficiency. The aim of this study was to investigate the influence of
      popping pretreatment and determine the optimal enzyme loading using a surface
      response design. RESULTS: The optimal doses of cellulase and xylanase enzymes
      were 23 FPU and 62 IU/g biomass, respectively. Using the optimized enzyme
      condition and popping pretreatment of rice straw (15% substrate loading, w/v), a
      sugar recovery of 0.567 g/g biomass (glucose; 0.394 g/g) was obtained in 48 h,
      which was significantly higher than that from untreated rice straw (total sugar
      recovery; 0.270 g/g biomass). Fermentation of the hydrolyzates by Saccharomyces
      cerevisiae resulted in 0.172 g ethanol/g biomass after 24 h, equivalent to 80.9%
      of the maximum theoretical yield (based on the amount of glucose in raw
      material). Changes in the chemical composition and surface area of rice straw
      were also investigated before and after popping pretreatment. The results showed
      little or no difference in chemical composition between the pretreated rice straw
      and the control. However, the surface area of pretreated rice straw increased
      twofold compared to the control. CONCLUSION: Popping pretreatment of rice straw
      can effectively improve downstream saccharification and fermentation, important
      for bioethanol production.

PMID- 24286245
TI  - Affective impact and electrocortical correlates of a psychotherapeutic
      microintervention: an ERP study of cognitive restructuring.
AB  - OBJECTIVE: Psychotherapy for depression emphasizes techniques that can help
      individuals regulate their moods. The present study investigated the affective
      impact and electrocortical correlates of cognitive restructuring, delivered as a
      90-minute psychotherapeutic microintervention in a dysphoric sample. METHOD:
      Participants (N = 92) who reported either low or high levels of dysphoric
      symptoms were randomly assigned to the restructuring microintervention, a control
      intervention or a no-intervention condition. We obtained recordings of event
      related potentials (ERPs) as well as mood self-ratings during an experimental
      session immediately after the psychotherapeutic microintervention and the control
      intervention in which a set of negatively valenced pictures (IAPS) was presented
      with different instructions. RESULTS: Whereas the restructuring intervention
      group and the control intervention group reported both increases in positive and
      decreases in negative affect from pre- to post-intervention, the three groups
      differed significantly on ERP measures. CONCLUSIONS: Findings provide support for
      current models of mechanisms of action in cognitive therapies.

PMID- 24286247
TI  - Experimental and theoretical charge density analysis of a bromoethyl sulfonium
      salt.
AB  - Bromoethyl sulfonium trifluoromethanesulfonate is a salt complex in which a
      sulfur atom makes three covalent bonds. This molecule has been proved to act as
      an efficient annulation reagent which results in formation of synthetically
      challenging and pharmaceutically important 4-, 5-, 6-, and 7-membered
      heterocycles in excellent yields. The charge density of the molecule was
      determined from both experimentally and theoretically derived diffraction data.
      The stereochemistry and electron density topology of the sulfonium group was
      analyzed. To understand the chemical reactivity of the molecule, the
      electrostatic potential difference between the two carbon atoms of the bromoethyl
      group was investigated. It has been considered that the hydrogen atoms on the
      carbon atom bound to sulfur are more acidic in character due to their vicinity
      with the triply covalently bonded positively charged sulfur atom. The
      electropositivity of the S-attached and Br-attached methylene groups are compared
      in the experimental and theoretical charge densities using topological atomic
      charges and electrostatic potential at the molecular surface. 

PMID- 24286246
TI  - Induction of heparanase by HPV E6 oncogene in head and neck squamous cell
      carcinoma.
AB  - High-risk human papillomavirus (HPV)-positive head and neck squamous cell
      carcinomas (HNSCCs) are highly invasive; however the identity of downstream
      effectors responsible for their aggressive phenotype remains underinvestigated.
      Here, we report that HPV-mediated up-regulation of heparanase enzyme can provide
      mechanistic explanation for augmented invasiveness of HPV-positive HNSCCs.
      Heparanase is the sole mammalian enzyme (endo-beta-d-glucuronidase) degrading
      heparan sulphate glycosaminoglycan, key polysaccharide of the extracellular
      matrix. Cleavage of heparan sulphate by heparanase leads to disassembly of
      extracellular barriers, enabling local invasion and metastatic spread of the
      tumour, and releases heparan sulphate-bound growth factors from the extracellular
      depots. Heparanase is tightly implicated in head and neck cancer progression;
      yet, molecular mechanisms underlying transcriptional activation of the heparanase
      gene in HNSCC are largely unknown. We found that HPV16 oncogene E6 is capable of
      inducing overexpression of heparanase in HNSCC. Notably, radiation treatment dose
      dependently suppresses E6-induced heparanase expression in vitro. Our results
      provide the first evidence for a functional involvement of HPV in heparanase
      induction in head and neck tumourigenesis and, given ongoing clinical testing of
      several heparanase-inhibiting compounds, offer important avenue for future
      therapeutic exploration in HNSCC, as well as other HPV-associated malignancies
      (i.e. cervical carcinoma).

PMID- 24286249
TI  - Factor VIII assay mimicking in vivo coagulation conditions.
AB  - Under certain circumstances, the determination of coagulation factor VIII (FVIII)
      is hampered by assay discrepancies between clotting and chromogenic approaches.
      These are observed in certain patients' plasma as well as in certain
      concentrates. We intended to develop a novel assay for the quantification of
      coagulation FVIII which reflects the physiological situation better than the
      established assays. It is based on plasma without chelation of divalent cations
      and simultaneously minimizes the generation of activated factors which could
      function as uncontrolled triggers of coagulation. FVIII deficient plasma is
      prepared with the aid of biotinylated antibodies against FVIII from normal plasma
      in presence of inhibitors of contact activation. To start the assay only tiny
      amounts of activated FIX serve as trigger. The FVIII determination is performed
      in a kinetic experiment and is based on the cleavage of a fluorogenic substrate
      for activated FX. FVIII concentrations between 0.01 and 1 IU mL(-1) are easily
      determined. Plasma-derived and recombinant FVIII concentrates were compared. All
      plasma-derived concentrates were found to contain FVIII activities within the
      specification of the manufacturer. Recombinant concentrates yielded only 35-50%
      of the claimed potency. The novel in vivo-like assay avoids the undue advantage
      or disadvantage of certain product characteristics by eliminating unphysiological
      assay conditions. Its usefulness could turn out in future experiments with plasma
      from haemophilia A patients.

PMID- 24286250
TI  - Endoproteolytic processing of the mammalian prion glycoprotein family.
AB  - Cellular prion protein (PrP(C)) misfolds to form infectivity-associated scrapie
      prion protein and generates C-terminal fragments C1 and C2 in healthy and prion
      infected animals. C1 cleavage occurs N-terminally of PrP(C)'s hydrophobic domain,
      whereas the larger C2 fragment is generated by cleavage at the end of the
      octarepeat region. As the PrP-like proteins Doppel and Shadoo (Sho) have been
      reported to inhabit similar membrane environments as PrP(C), we investigated
      endoproteolysis by using a panel of mutant alleles. Doppel undergoes efficient in
      vivo cleavage at a C1 site mapped to the start of the globular domain, which is a
      structurally similar cleavage site to that in PrP(C). Sho is processed to C1 and
      C2 fragments, and proved refractory to mutagenesis to inactivate C1 cleavage. As
      a reciprocal product of C1 cleavage, Sho also engenders a metabolically stable N1
      fragment with a C-terminus after its hydrophobic domain, an observation that may
      account for N1's association with membrane and/or cellular fractions in vitro and
      in vivo. Our data indicate that glycosylation status and yet to be identified
      proteases modulate internal C1 and C2 proteolysis events within the mammalian
      prion protein family.

PMID- 24286251
TI  - Misreporting signs of child abuse: the role of decision-making and outcome
      information.
AB  - Two studies provided evidence that a decision to report an ambiguous case of
      child abuse affected subsequent memory of the case information, such that
      participants falsely recognized details that were not presented in the original
      information, but that are schematically associated with child abuse. Moreover,
      post-decision information that the child had later died from abuse influenced the
      memory reports of participants who had chosen not to report the case, increasing
      their reports of false schema-consistent details. This suggests that false
      decision-consistent memories are primarily due to sense-making, schematic
      processing rather than the motivation to justify the decision. The present
      findings points to an important mechanism by which decision information can
      become distorted in retrospect, and emphasize the difficulties of improving
      future decision-making by contemplating past decisions. The results also indicate
      that decisions may generate false memories in the apparent absence of external
      suggestion or misleading information. Implications for decision-making theory,
      and applied practices are discussed. 

PMID- 24286248
TI  - Human parainfluenza virus in patients with influenza-like illness from Central
      and South America during 2006-2010.
AB  - BACKGROUND: Human parainfluenza viruses (HPIVs) are common viral causes of
      community-acquired pneumonia, particularly in children. The four types of HPIV
      have world-wide distribution; however, limited information exists about the
      epidemiological profile of HPIV in Latin-America. OBJECTIVE: Provide
      epidemiologic and phylogenetic information about HPIVs that circulated in Latin
      America between 2006 and 2010 to better characterize the extent and variability
      of this respiratory virus in the region. METHODS: Oropharyngeal swabs,
      demographic data and clinical characteristics were obtained from individuals with
      influenza-like illness in 10 Latin-American countries between 2006-2010.
      Specimens were analyzed with culture and molecular methods. RESULTS: A total of
      30 561 individuals were enrolled; 991 (3.2%) were HPIV positive. Most infected
      participants were male (53.7%) and under 5 years of age (68.7%). The HPIV type
      most frequently isolated was HPIV-3 (403, 40.7%). In 66/2007 (3.3%) hospitalized
      individuals, HPIV was identified. The most frequent symptoms at enrollment were
      cough and rhinorrhea. We identified certain patterns for HPIV-1, -2 and -3 in
      specific cities. Phylogenetic analysis revealed a homogeneous distribution in the
      region. CONCLUSIONS: In the current scenario, no vaccine or treatment is
      available for this pathogen. Our results contribute to the scarce epidemiologic
      and phylogenetic information of HPIV in the region that could support the
      development of specific management.

PMID- 24286253
TI  - Kangaroo mother care in the neonatal intensive care unit: staff attitudes and
      beliefs and opportunities for parents.
AB  - AIM: To compare attitudes towards Kangaroo mother care (KMC) among staff in two
      high-tech neonatal intensive care units, which provided parents with different
      opportunities to get involved in their infants' care. METHOD: Questionnaires were
      completed by healthcare staff in Unit A, which provided parents with unrestricted
      access so that they could provide continuous KMC, and Unit B, where parents could
      only practice KMC intermittently. RESULTS: Unit A staff were more positive about
      the benefits and use of KMC, including its use in unstable infants, and rated
      their knowledge and practical skills more highly than staff in the other unit.
      Unit B staff also appreciated the method, but expressed more hesitation in using
      it with unstable infants. In particular, they stressed the need to adapt the
      physical environment of the NICU to enable parents to stay with their infants and
      practice the method. CONCLUSION: Staff working in the NICU that gave parents
      unrestricted access were more positive about KMC than staff in the NICU that
      offered limited opportunities for parents to stay with their children. This
      finding suggests that it is important to eliminate unjustifiable obstacles to the
      presence of parents in the NICU, so that they can provide KMC.

PMID- 24286254
TI  - Factors affecting the selectivity of nanoparticle-based photoinduced damage in
      free and xenografted chorioallantoic membrane model.
AB  - Abstract Background: Photodynamic therapy (PDT) is a minimally invasive treatment
      modality for selective destruction of tumours. Critical anatomical structures,
      like blood vessels in close proximity to the tumour, could be harmed during PDT.
      Purpose: This study aims to discriminate the photoinduced response of normal and
      cancerous tissues to photodamage induced by liposomal formulations of meta
      tetra(hydroxyphenyl)chlorin (mTHPC). Methods: Normal vascular and cancerous
      tissues were represented, respectively, by free and xenografted in vivo model of
      chick chorioallantoic membrane (CAM). Eggs received an intravenous administration
      of plain (Foslip(r)) or stabilised formulations (Fospeg(r)). Drug release and
      liposome destruction were, respectively, determined by photoinduced quenching and
      nanoparticle tracking analysis. PDT was performed at different drug-light
      intervals (DLI) with further assessment of photothrombic activity, tumoritropism
      and photoinduced necrosis. Results: Compared to Foslip(r), Fospeg(r) demonstrated
      significantly higher stability, slower drug release, better tumoricidal effect
      and lower damage to the normal vasculature at already 1 h DLI. Discussion: This
      work suggests that nanoparticle-based PDT selectivity could be optimised by
      analyzing the photoinduced damage of healthy and tumour tissues. Conclusion: In
      fine, Fospeg(r) appeared to be the ideal candidate in clinical context due to its
      potential to destroy tumours and reduce vascular damage to normal tissues at
      short DLI.

PMID- 24286255
TI  - Sinus arrest and asystole caused by a peripherally inserted central catheter.
AB  - BACKGROUND: Transient bradycardia in the critical care setting is frequently
      caused by hypoxemia or oropharyngeal manipulation. Central lines have been
      associated with a variety of cardiac arrhythmias, but sinus arrest and asystole
      have not been previously reported. METHODS: A 38-year-old woman with multisystem
      organ failure had several episodes of prolonged sinus arrest, slow junctional
      escape rhythm, and periods of asystole lasting over 6 seconds. The cause of the
      repetitive bradyarrhythmia was evaluated by clinical observation including the
      response to parasympatholytic agents, by detailed analysis of rhythm strips, and
      review of cardiac imaging studies. RESULTS: The episodes of bradycardia did not
      coincide with orotracheal manipulation, were not prevented by escalating doses of
      glycopyrrolate, and were not accompanied by AV conduction disturbance as is
      frequently seen during a transient increase in vagal tone. Review of the
      patient's chest X-ray and chest CT revealed that the tip of a peripherally
      inserted central catheter migrated to the vicinity of the sinoatrial node.
      Removal of the catheter resulted in prompt resolution of the episodes of sinus
      arrest. CONCLUSIONS: This case demonstrates that migration of a peripherally
      inserted central catheter to the sinoatrial node can provoke prolonged sinus
      bradycardia, sinus arrest and asystole.

PMID- 24286256
TI  - The interplay between the GATA transcription factors AreA, the global nitrogen
      regulator and AreB in Fusarium fujikuroi.
AB  - Nitrogen metabolite repression (NMR) in filamentous fungi is controlled by the
      GATA transcription factors AreA and AreB. While AreA mainly acts as a positive
      regulator of NMR-sensitive genes, the role of AreB is not well understood. We
      report the characterization of AreB and its interplay with AreA in the
      gibberellin-producing fungus Fusarium fujikuroi. The areB locus produces three
      different transcripts that each code for functional proteins fully complementing
      the areB deletion mutant that influence growth and secondary metabolism. However,
      under nitrogen repression, the AreB isoforms differ in subcellular localization
      indicating distinct functions under these conditions. In addition, AreA and two
      isoforms of AreB colocalize in the nucleus under low nitrogen, but their nuclear
      localization disappears under conditions of high nitrogen. Using a bimolecular
      fluorescence complementation (BiFC) approach we showed for the first time that
      one of the AreB isoforms interacts with AreA when starved of nitrogen. Cross
      species complementation revealed that some AreB functions are retained between F.
      fujikuroi and Aspergillus nidulans while others have diverged. By comparison to
      other fungi where AreB was postulated to function as a negative counterpart of
      AreA, AreB can act as both repressor and activator of transcription in F.
      fujikuroi. 

PMID- 24286252
TI  - Close association of active nitrifiers with Beggiatoa mats covering deep-sea
      hydrothermal sediments.
AB  - Hydrothermal sediments in the Guaymas Basin are covered by microbial mats that
      are dominated by nitrate-respiring and sulphide-oxidizing Beggiatoa. The presence
      of these mats strongly correlates with sulphide- and ammonium-rich fluids venting
      from the subsurface. Because ammonium and oxygen form opposed gradients at the
      sediment surface, we hypothesized that nitrification is an active process in
      these Beggiatoa mats. Using biogeochemical and molecular methods, we measured
      nitrification and determined the diversity and abundance of nitrifiers.
      Nitrification rates ranged from 74 to 605 MUmol N l(-1)  mat day(-1), which
      exceeded those previously measured in hydrothermal plumes and other deep-sea
      habitats. Diversity and abundance analyses of archaeal and bacterial ammonia
      monooxygenase subunit A genes, archaeal 16S ribosomal RNA pyrotags and
      fluorescence in situ hybridization confirmed that ammonia- and nitrite-oxidizing
      microorganisms were associated with Beggiatoa mats. Intriguingly, we observed
      cells of bacterial and potential thaumarchaeotal ammonia oxidizers attached to
      narrow, Beggiatoa-like filaments. Such a close spatial coupling of nitrification
      and nitrate respiration in mats of large sulphur bacteria is novel and may
      facilitate mat-internal cycling of nitrogen, thereby reducing loss of
      bioavailable nitrogen in deep-sea sediments.

PMID- 24286257
TI  - Reusable heat-sensitive phantom for precise estimation of thermal profile in
      hyperthermia application.
AB  - PURPOSE: The emergence of thermal modalities has promoted the use of heat
      sensitive phantoms for calibration, measurement, and verification purposes.
      However, development of durable phantoms with high precision ability to represent
      the temperature distribution remains a challenge. This study aims to introduce a
      reusable phantom that provides an accurate assessment of the heated region in
      various thermal modalities. MATERIALS AND METHODS: The phantom contains a
      thermochromic dye that is transparent blue at room temperature and becomes
      colourless after exceeding a threshold temperature. In order to determine the
      threshold temperature of the phantom, spectrophotometry analysis was performed.
      The various thermal (specific heat, thermal conductivity, melting point and
      latent heat of melting) and acoustic (sound speed, attenuation) properties of
      this phantom were measured and compared with those of the reference phantom
      without dye. The application of this phantom for radio-frequency and magnetic
      resonance guided focused ultrasound modalities was also examined. RESULTS: The
      spectrophotometry analysis showed a threshold temperature of 50 +/- 3  degrees C
      for this phantom. The results also demonstrated a 6  degrees C difference between
      the onset and ending temperatures of the discolouration process. Moreover, the
      starting temperature of colouration during cooling was found to be 4  degrees C
      lower than the ending temperature of discolouration. The sound speed,
      attenuation, specific heat, thermal conductivity and melting point of the heat
      sensitive phantom were statistically equal to those of the reference phantom;
      however, the latent heat, and onset temperature of the melting of the heat
      sensitive phantom were decreased by addition of the dye. CONCLUSIONS: The
      developed phantom is applicable for accurate evaluation of temperature variations
      in various thermal modalities.

PMID- 24286258
TI  - Risk of norovirus gastroenteritis from consumption of vegetables irrigated with
      highly treated municipal wastewater--evaluation of methods to estimate sewage
      quality.
AB  - Quantitative microbial risk assessment was used to assess the risk of norovirus
      gastroenteritis associated with consumption of raw vegetables irrigated with
      highly treated municipal wastewater, using Melbourne, Australia as an example. In
      the absence of local norovirus concentrations, three methods were developed: (1)
      published concentrations of norovirus in raw sewage, (2) an epidemiological
      method using Melbourne prevalence of norovirus, and (3) an adjustment of method 1
      to account for prevalence of norovirus. The methods produced highly variable
      results with estimates of norovirus concentrations in raw sewage ranging from
      10(4) per milliliter to 10(7) per milliliter and treated effluent from 1 * 10(-3)
      per milliliter to 3 per milliliter (95th percentiles). Annual disease burden was
      very low using method 1, from 4 to 5 log10 disability adjusted life years (DALYs)
      below the 10(-6) threshold (0.005-0.1 illnesses per year). Results of method 2
      were higher, with some scenarios exceeding the threshold by up to 2 log10 DALYs
      (up to 95,000 illnesses per year). Method 3, thought to be most representative of
      Melbourne conditions, predicted annual disease burdens >2 log10 DALYs lower than
      the threshold (~ 4 additional cases per year). Sensitivity analyses demonstrated
      that input parameters used to estimate norovirus concentration accounted for much
      of the model output variability. This model, while constrained by a lack of
      knowledge of sewage concentrations, used the best available information and sound
      logic. Results suggest that current wastewater reuse behaviors in Melbourne are
      unlikely to cause norovirus risks in excess of the annual DALY health target.

PMID- 24286260
TI  - More than a feeling: new approach required for assessing immunosuppression.

PMID- 24286259
TI  - Genome-wide identification of genes involved in the positive and negative
      regulation of acetic acid-induced programmed cell death in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: Acetic acid is mostly known as a toxic by-product of alcoholic
      fermentation carried out by Saccharomyces cerevisiae, which it frequently
      impairs. The more recent finding that acetic acid triggers apoptotic programmed
      cell death (PCD) in yeast sparked an interest to develop strategies to modulate
      this process, to improve several biotechnological applications, but also for
      biomedical research. Indeed, acetate can trigger apoptosis in cancer cells,
      suggesting its exploitation as an anticancer compound. Therefore, we aimed to
      identify genes involved in the positive and negative regulation of acetic acid
      induced PCD by optimizing a functional analysis of a yeast Euroscarf knock-out
      mutant collection. RESULTS: The screen consisted of exposing the mutant strains
      to acetic acid in YPD medium, pH 3.0, in 96-well plates, and subsequently
      evaluating the presence of culturable cells at different time points. Several
      functional categories emerged as greatly relevant for modulation of acetic acid
      induced PCD (e.g.: mitochondrial function, transcription of glucose-repressed
      genes, protein synthesis and modifications, and vesicular traffic for protection,
      or amino acid transport and biosynthesis, oxidative stress response, cell growth
      and differentiation, protein phosphorylation and histone deacetylation for its
      execution). Known pro-apoptotic and anti-apoptotic genes were found, validating
      the approach developed. Metabolism stood out as a main regulator of this process,
      since impairment of major carbohydrate metabolic pathways conferred resistance to
      acetic acid-induced PCD. Among these, lipid catabolism arose as one of the most
      significant new functions identified. The results also showed that many of the
      cellular and metabolic features that constitute hallmarks of tumour cells (such
      as higher glycolytic energetic dependence, lower mitochondrial functionality,
      increased cell division and metabolite synthesis) confer sensitivity to acetic
      acid-induced PCD, potentially explaining why tumour cells are more susceptible to
      acetate than untransformed cells and reinforcing the interest in exploiting this
      acid in cancer therapy. Furthermore, our results clearly establish a connection
      between cell proliferation and cell death regulation, evidencing a conserved
      developmental role of programmed cell death in unicellular eukaryotes.
      CONCLUSIONS: This work advanced the characterization of acetic acid-induced PCD,
      providing a wealth of new information on putative molecular targets for its
      control with impact both in biotechnology and biomedicine.

PMID- 24286261
TI  - Acute myeloid leukemia presenting with panhypopituitarism or diabetes insipidus:
      a case series with molecular genetic analysis and review of the literature.
AB  - Central diabetes insipidus (DI) is a rare finding in patients with acute myeloid
      leukemia (AML), usually occurring in patients with chromosome 3 or 7
      abnormalities. We describe four patients with AML and concurrent DI and a fifth
      patient with AML and panhypopituitarism. Four of five patients had monosomy 7.
      Three patients had chromosome 3q21q26/EVI-1 gene rearrangements. The molecular
      genotype of patients with AML and DI is not known. Therefore, we performed gene
      sequencing of 30 genes commonly mutated in AML in three patients with available
      leukemia cell DNA. One patient had no identifiable mutations, and two had RUNX1
      F158S mutations.

PMID- 24286262
TI  - Central nervous system involvement in diffuse large B-cell lymphoma: an analysis
      of risks and prevention strategies in the post-rituximab era.
AB  - Central nervous system (CNS) relapse in patients with diffuse large B-cell
      lymphoma (DLBCL) occurs infrequently (approximately 5%), but is almost
      universally fatal. Controversy exists regarding which factors most reliably
      identify high risk patients in the post-rituximab era. Clarification is also
      needed regarding the value of prophylaxis strategies when contemporary rituximab
      based chemotherapy regimens (chemoimmunotherapy) are used. A systematic review
      with focus on the era of chemoimmunotherapy has been performed. Involvement of >
      1 extranodal site plus an elevated lactate dehydrogenase level identifies
      individuals at highest risk (> 20%) for CNS recurrence who merit additional
      evaluation. Only certain solitary extranodal sites (testis, kidney and breast,
      but not bones, orbit or epidural space) appear to confer higher risk in patients
      receiving chemoimmunotherapy. Data from studies employing modern regimens suggest
      that intrathecal prophylaxis is ineffective even for high risk populations.
      Systemic prophylaxis (e.g. high dose methotrexate) may be useful, but does not
      have strong support in the literature. A significant portion of patients with
      high risk features (~25%) may already have subclinical CNS disease, which
      requires alternative detection and treatment strategies. Flow cytometry is a
      promising approach with increased sensitivity. Widespread use of this approach
      could redefine what risk and prophylaxis mean. An algorithm for incorporating
      risk factors, evaluation and treatment is presented.

PMID- 24286263
TI  - Use of positron emission tomography-computed tomography in the management of
      patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.
AB  - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) cells typically
      have low 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) avidity, and patients with CLL
      have an increased risk of developing FDG-avid aggressive lymphomas, second
      malignancies and infections. We hypothesized that FDG positron emission
      tomography-computed tomography (PET-CT) of the trunk is a sensitive method of
      detecting these complications in patients with CLL. Of the of 2299 patients with
      CLL seen in the Division of Hematology at Mayo Clinic Rochester between 1 January
      2006 and 31 December 2011, 272 (11.8%) had 526 PET-CT scans and 472 (89.7%) of
      these were reported as abnormal. Among the 293 (55.7%) PET-CT scans used for
      routine evaluation of CLL, the PET component was of clinical value in only one
      instance. In contrast, in 83 (30.5%) patients, PET-CT scans used to evaluate new
      clinical complications localized high FDG-avidity lesions for biopsies. This
      resulted in clinically relevant new diagnoses in 32 patients, including those
      with more aggressive lymphoma (n = 16), non-hematological malignancies (n = 8)
      and opportunistic infections (n = 3). Twenty-seven patients had high FDG-avidity
      CLL, which was associated with prominent lymph node proliferation centers, an
      increased frequency of poor prognostic factors (17p13 deletion, unmutated
      immunoglobulin heavy chain variable gene [IGHV], expression of ZAP-70 and CD38)
      and a shorter overall survival. We conclude that FDG PET scans should not be used
      for routine surveillance of patients with CLL. However PET-CT scans are
      sensitive, but not specific, for detection of aggressive lymphomas, other cancers
      and systemic infections in patients with CLL.

PMID- 24286264
TI  - Role of the A(2B) receptor-adenosine deaminase complex in colonic dysmotility
      associated with bowel inflammation in rats.
AB  - BACKGROUND AND PURPOSE: Adenosine A(2B) receptors regulate several physiological
      enteric functions. However, their role in the pathophysiology of intestinal
      dysmotility associated with inflammation has not been elucidated. Hence, we
      investigated the expression of A2B receptors in rat colon and their role in the
      control of cholinergic motility in the presence of bowel inflammation.
      EXPERIMENTAL APPROACH: Colitis was induced by 2,4-dinitrobenzenesulfonic acid
      (DNBS). Colonic A(2B) receptor expression and localization were examined by RT
      PCR and immunofluorescence. The interaction between A(2B) receptors and adenosine
      deaminase was assayed by immunoprecipitation. The role of A(2B) receptors in the
      control of colonic motility was examined in functional experiments on
      longitudinal muscle preparations (LMPs). KEY RESULTS: A(2B) receptor mRNA was
      present in colon from both normal and DNBS-treated rats but levels were increased
      in the latter. A(2B) receptors were predominantly located in the neuromuscular
      layer, but, in the presence of colitis, were increased mainly in longitudinal
      muscle. Functionally, the A(2B) receptor antagonist MRS 1754 enhanced both
      electrically-evoked and carbachol-induced cholinergic contractions in normal
      LMPs, but was less effective in inflamed tissues. The A(2B) receptor agonist NECA
      decreased colonic cholinergic motility, with increased efficacy in inflamed LMP.
      Immunoprecipitation and functional tests revealed a link between A(2B) receptors
      and adenosine deaminase, which colocalize in the neuromuscular compartment.
      CONCLUSIONS AND IMPLICATIONS: Under normal conditions, endogenous adenosine
      modulates colonic motility via A2B receptors located in the neuromuscular
      compartment. In the presence of colitis, this inhibitory control is impaired due
      to a link between A2B receptors and adenosine deaminase, which catabolizes
      adenosine, thus preventing A(2B) receptor activation.

PMID- 24286265
TI  - Investigation of the stabilizing effects of hydroxyethyl cellulose on LDH during
      freeze drying and freeze thawing cycles.
AB  - The objective of this study was to investigate both the cryoprotective and
      lyoprotective effects of the polymer hydroxyethyl cellulose (HEC) on the model
      protein lactate dehydrogenase (LDH) during freeze thawing and freeze drying
      cycles. The effect of annealing on both protein stability and the physical state
      of HEC was evaluated. HEC was used as a sole excipient in the protein
      formulations, and its stabilizing was compared to that of other excipients which
      are commonly used in freeze dried protein formulations. Furthermore, other
      quality aspects of the freeze dried samples containing solely HEC were
      investigated, such as, reconstitution time and product elegance. Protein
      stability was evaluated functionally by measuring the activity recovery of the
      model protein LDH. The physical state of HEC after freeze drying was investigated
      and compared to this of other studied solutes using differential scanning
      calorimetry and X-ray powder diffractometry. HEC showed superior cryoprotective
      effects on LDH during freeze thawing, and considerable lyoprotective effects
      during the freeze drying process. Annealing had limited influence on the
      stabilizing effect of HEC. The extensive reconstitution times of the HEC
      lyophilisates could be greatly improved by incorporation of the surfactant Tween
      80 into the formulations prior to freeze drying.

PMID- 24286266
TI  - Obituary: pulmonary artery catheter 1970 to 2013.
AB  - The birth of the intermittent injectate-based conventional pulmonary artery
      catheter (fondly nicknamed PAC) was proudly announced in the New England Journal
      of Medicine in 1970 by his parents HJ Swan and William Ganz. PAC grew rapidly,
      reaching manhood in 1986 where, in the US, he was shown to influence the
      management of over 40% of all ICU patients. His reputation, however, was
      tarnished in 1996 when Connors and colleagues suggested that he harmed patients.
      This was followed by randomized controlled trials demonstrating he was of little
      use. Furthermore, reports surfaced suggesting that he was unreliable and
      inaccurate. It also became clear that he was poorly understood and
      misinterpreted. Pretty soon after that, a posse of rivals (bedside
      echocardiography, pulse contour technology) moved into the neighborhood and
      claimed they could assess cardiac output more easily, less invasively and no less
      reliably. To make matter worse, dynamic assessment of fluid responsiveness (pulse
      pressure variation, stroke volume variation and leg raising) made a mockery of
      his 'wedge' pressure. While a handful of die-hard followers continued to promote
      his mission, the last few years of his existence were spent as a castaway until
      his death in 2013. His cousin (the continuous cardiac output PAC) continues to
      eke a living mostly in cardiac surgery patients who need central access anyway.
      This paper reviews the rise and fall of the conventional PAC. 

PMID- 24286267
TI  - Vulnerability to traumatic stress in fibromyalgia patients: 19 month follow-up
      after the great East Japan disaster.
AB  - INTRODUCTION: The aim of this study was to investigate vulnerability and long
      term influence of traumatic stress caused by the Great East Japan Disaster which
      occurred on March 11, 2011, in patients with fibromyalgia, which is a chronic
      pain syndrome probably involving central sensitization. METHODS: A total of 60
      female patients with fibromyalgia were compared with female patients with
      rheumatoid arthritis (RA, n = 23) as another chronic pain disease, and with
      female healthy controls (HC, n = 26) in the observational study. To evaluate
      responses to traumatic stress, the scores of Impact of Event Scale-Revised (IES
      R) were assessed one month after the disaster and every six months until 19
      months after the disaster. We also evaluated levels of depression during the
      study period. To know the score of IES-R of patients with fibromyalgia during
      usual living, we assessed IES-R in another population of fibromyalgia patients
      without exposure to a great disaster. RESULTS: The mean score of IES-R one month
      after the disaster in the fibromyalgia group (24.6 [SD 18.9]) was significantly
      higher than that of RA group (13.4 [SD 14.5]) or HC group (9.1 [9.2]) (F = 9.96,
      p < 0.0001). However, the mean score of IES-R in fibromyalgia patients without
      exposure to a great disaster was (20.3 [SD 18.7]), which was almost the same
      value as the fibromyalgia group seven months after the disaster (20.2 [SD 19.5]).
      Repeated measures analysis of variance showed significant effect of time course
      in the depression-related symptoms (F = 6.68, P = 0.001), and a post-hoc test
      revealed that the number of depression-related symptoms one month before the
      disaster was significantly different from other time points until 19 months after
      the disaster, respectively. CONCLUSIONS: Although response to acute stress
      induced by the great earthquake was likely to be settled within seven months
      after the disaster, depression-related symptoms have been increasing for more
      than one year after the disaster, despite exclusion of patients with major
      depression at baseline. This long-lasting worsening of depression-related
      symptoms may have been in response to chronic stress induced by the fear of
      radiation due to the nuclear power disaster. These findings suggest that patients
      with fibromyalgia are vulnerable to chronic stress rather than acute stress.

PMID- 24286268
TI  - Functional outcome and prognostic factors in anti-Jo1 patients with
      antisynthetase syndrome.
AB  - INTRODUCTION: The aims of this present study were firstly to assess the outcome,
      including functional course, in anti-Jo1 positive patients with antisynthetase
      syndrome (ASS), and secondly to determine predictive parameters of poor outcome
      in these patients. METHODS: The medical records of 86 consecutive anti-Jo1
      patients with ASS were reviewed in 4 academic centers. RESULTS: 13 patients
      (15.1%) achieved remission of ASS, whereas 55 (63.9%) improved and 18 (20.9%)
      deteriorated in their clinical status. Both steroid and cytotoxic drugs could be
      discontinued in only 4.7% of patients. ASS was associated with decreased quality
      of life at long-term follow-up: only 69.2% of patients considered to be in
      remission experienced a return to previous normal activities; and 24.7% of other
      patients with non-remitting ASS still had a marked reduction of activities (as
      shown by the disability scale of the Health Assessment Questionnaire). Decreased
      quality of life was further due to calcinosis cutis (8.1%) and adverse effects of
      steroid therapy (36%). Factors associated with ASS deterioration were older age,
      pulmonary and esophageal involvement, calcinosis cutis and cancer. Higher anti
      Jo1 levels were further associated with disease severity in ASS patients.
      CONCLUSIONS: The present study shows high morbidity related to ASS. Furthermore,
      we suggest that patients with predictive factors of ASS deterioration may require
      more aggressive therapy. Our findings also suggest that in anti-Jo1 patients with
      severe esophageal manifestations, combined high dose steroids and intravenous
      immunoglobulins might be proposed as the first line therapy. Finally, as cancer
      occurred in 14% of anti-Jo1 patients, our findings underscore that the search for
      cancer should be performed in these patients.

PMID- 24286270
TI  - Raw starch conversion by Saccharomyces cerevisiae expressing Aspergillus
      tubingensis amylases.
AB  - BACKGROUND: Starch is one of the most abundant organic polysaccharides available
      for the production of bio-ethanol as an alternative transport fuel. Cost
      effective utilisation of starch requires consolidated bioprocessing (CBP) where a
      single microorganism can produce the enzymes required for hydrolysis of starch,
      and also convert the glucose monomers to ethanol. RESULTS: The Aspergillus
      tubingensis T8.4 alpha-amylase (amyA) and glucoamylase (glaA) genes were cloned
      and expressed in the laboratory strain Saccharomyces cerevisiae Y294 and the semi
      industrial strain, S. cerevisiae Mnualpha1. The recombinant AmyA and GlaA
      displayed protein sizes of 110-150 kDa and 90 kDa, respectively, suggesting
      significant glycosylation in S. cerevisiae. The Mnualpha1[AmyA-GlaA] and
      Y294[AmyA-GlaA] strains were able to utilise 20 g l-1 raw corn starch as sole
      carbohydrate source, with ethanol titers of 9.03 and 6.67 g l-1 (0.038 and 0.028
      g l-1 h-1), respectively, after 10 days. With a substrate load of 200 g l-1 raw
      corn starch, Mnualpha1[AmyA-GlaA] yielded 70.07 g l-1 ethanol (0.58 g l-1 h-1)
      after 120 h of fermentation, whereas Y294[AmyA-GlaA] was less efficient at 43.33
      g l-1 ethanol (0.36 g l-1 h-1). CONCLUSIONS: In a semi-industrial amylolytic S.
      cerevisiae strain expressing the A. tubingensis alpha-amylase and glucoamylase
      genes, 200 g l-1 raw starch was completely hydrolysed (saccharified) in 120 hours
      with 74% converted to released sugars plus fermentation products and the
      remainder presumably to biomass. The single-step conversion of raw starch
      represents significant progress towards the realisation of CBP without the need
      for any heat pretreatment. Furthermore, the amylases were produced and secreted
      by the host strain, thus circumventing the need for exogenous amylases.

PMID- 24286269
TI  - Rituximab and abatacept but not tocilizumab impair antibody response to
      pneumococcal conjugate vaccine in patients with rheumatoid arthritis.
AB  - INTRODUCTION: The objective of the study was to investigate the impact of newer
      biologic treatments including rituximab, abatacept and tocilizumab on antibody
      response following pneumococcal vaccination using a 7-valent conjugate vaccine in
      patients with established rheumatoid arthritis (RA). METHODS: Patients with RA
      receiving rituximab, abatacept or tocilizumab as monotherapy or combined with
      methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F
      and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination
      using standardised ELISA. Geometric mean antibody levels (GML) were calculated.
      Antibody response (AR) was defined as the ratio between post- and pre-vaccination
      antibody levels and a positive antibody response (posAR) was AR >= 2. RESULTS: In
      total, 88 patients were enrolled in the study. Of 55 patients treated with
      rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n =
      17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX
      in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab
      had significantly lower AR compared to those on tocilizumab, as well as compared
      to previously reported RA patients on MTX and controls (spondylarthropathy
      patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on
      rituximab monotherapy and no patient on rituximab + MTX had posAR for both
      serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and
      50%. CONCLUSION: In this cohort of patients with established RA, treatment with
      rituximab and abatacept was associated with diminished antibody response but this
      was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated
      during ongoing tocilizumab treatment seems to be associated with sufficient
      antibody response. Pneumococcal vaccination should preferably be encouraged
      before initiation of rituximab or abatacept treatment. TRIAL REGISTRATION:
      NCT00828997 and EudraCT EU 2007-006539-29.

PMID- 24286271
TI  - Look local: the value of cancer surveillance and reporting by American Indian
      clinics.
AB  - INTRODUCTION: Cancer incidence and mortality rates for American Indians in the
      Northern Plains region of the United States are among the highest in the nation.
      Reliable cancer surveillance data are essential to help reduce this burden;
      however, racial data in state cancer registries are often misclassified, and
      cases are often underreported. METHODS: We used a community-based participatory
      research approach to conduct a retrospective ascertainment of cancer cases in
      clinic medical records over a 9-year period (1995-2003) and compared the results
      with the state cancer registry to evaluate missing or racially misclassified
      cases. Six tribal and/or urban Indian clinics participated in the study. The
      project team consisted of participating clinics, a state cancer registry, a
      comprehensive cancer center, an American Indian/Alaska Native Leadership
      Initiative on Cancer, and a set of diverse organizational partners. Clinic
      personnel were trained by project staff to accurately identify cancer cases in
      clinic records. These records were then matched with the state cancer registry to
      assess misclassification and underreporting. RESULTS: Forty American Indian cases
      were identified that were either missing or misclassified in the state registry.
      Adding these cases to the registry increased the number of American Indian cases
      by 21.3% during the study period (P = .05). CONCLUSIONS: Our results indicate
      that direct reporting of cancer cases by tribal and urban Indian health clinics
      to a state cancer registry improved the quality of the data available for cancer
      surveillance. Higher-quality data can advance the efforts of cancer prevention
      and control stakeholders to address disparities in Native communities.

PMID- 24286272
TI  - Emergency department use by centenarians: the 2008 Nationwide Emergency
      Department Sample.
AB  - INTRODUCTION: Older adults have higher rates of emergency department use than do
      younger adults, and the number of centenarians is expected to increase. The
      objective of this study was to examine centenarians' use of the emergency
      department in the United States, including diagnoses, charges, and disposition.
      METHODS: The 2008 Nationwide Emergency Department Sample, Healthcare Cost and
      Utilization Project, Agency for Healthcare Research and Quality provided
      encounter-level data on emergency department visits and weights for producing
      nationwide estimates. From this data set, we collected patient characteristics
      including age, sex, primary diagnosis, and disposition. We used chi(2) tests and
      t tests to test for significant differences among people aged 80 to 89, 90 to 99,
      and 100 years or older. RESULTS: Centenarians had a lower rate of emergency
      department use than those aged 90 to 99 (736 per 1,000 vs 950 per 1,000; P <
      .05). We found no significant difference in use between centenarians and those
      aged 80 to 89. The most common diagnoses for centenarians were superficial
      injuries (5.8% of visits), pneumonia (5.1%), and urinary tract infections (5.1%).
      Centenarians were more likely to visit the emergency department for fall-related
      injuries (21.5%) than those aged 80 to 89 (14.1%; P < .05) and 90 to 99 (18.7%; P
      < .05). Centenarians were more likely to die in the emergency department (2.0%)
      than were those aged 80 to 89 (0.6%; P < .05) and 90 to 99 (0.7%; P < .05).
      CONCLUSION: Centenarians in emergency departments in the United States have
      different diagnoses, conditions, and outcomes than other older Americans.

PMID- 24286273
TI  - Multiple chronic conditions and limitations in activities of daily living in a
      community-based sample of older adults in New York City, 2009.
AB  - INTRODUCTION: Nationally, 60% to 75% of older adults have multiple (2 or more)
      chronic conditions (MCCs), and the burden is even higher among low-income,
      racial/ethnic minority populations. MCCs limit activities of daily living (ADLs),
      yet this association is not well characterized outside of clinical populations.
      We examined the association of MCCs with ADLs in a racially/ethnically diverse
      population of low-income older adults living in New York City public housing.
      METHODS: A representative sample of 1,036 New York City Housing Authority
      residents aged 65 or older completed a telephone survey in June 2009. We examined
      the association of up to 5 chronic conditions with basic ADL (BADL) limitations,
      adjusting for potential confounders by using logistic regression. RESULTS: Of
      respondents, 28.7% had at least 1 BADL limitation; 92.9% had at least 1 chronic
      condition, and 79.0% had MCCs. We observed a graded association between at least
      1 BADL limitation and number of chronic conditions (using 0 or 1 condition as the
      reference group): adjusted odds ratio (AOR) for 3 conditions was 2.2 (95%
      confidence interval [CI], 1.3-3.9); AOR for 4 conditions, 4.3 (95% CI, 2.5-7.6);
      and AOR for 5 conditions, 9.2 (95% CI, 4.3-19.5). CONCLUSION: Prevalence of BADL
      limitations is high among low-income older adults and increases with number of
      chronic conditions. Initiating prevention of additional conditions and treating
      disease constellations earlier to decrease BADL limitations may improve aging
      outcomes in this population.

PMID- 24286274
TI  - Sociocultural tailoring of a healthy lifestyle intervention to reduce
      cardiovascular disease and type 2 diabetes risk among Latinos.
AB  - BACKGROUND: Suboptimal lifestyle factors in combination with genetic
      susceptibility contribute to cardiovascular disease and type 2 diabetes risk
      among Latinos. We describe a community-academic collaboration that developed and
      explored the feasibility of implementing a socioculturally tailored, healthy
      lifestyle intervention integrating genomics and family history education to
      reduce risk of cardiovascular disease and type 2 diabetes among Latinos.
      COMMUNITY CONTEXT: The community-based participatory research was conducted with
      communities in Kentucky, which has a rapidly growing Latino population. This
      growth underscores the need for socioculturally appropriate health resources.
      METHODS: Su Corazon, Su Vida (Your Heart, Your Life) is a Spanish-language,
      healthy lifestyle educational program to reduce cardiovascular disease and type 2
      diabetes risk among Latinos. Twenty natural leaders from an urban Latino
      community in Kentucky participated in sociocultural tailoring of the program and
      development of a genomics and family history module. The tailored program was
      presented to 22 participants to explore implementation feasibility and assess
      appropriateness for community use. Preintervention and postintervention
      assessments of genomic knowledge and lifestyle behaviors and qualitative
      postintervention evaluations were conducted. OUTCOMES: Postintervention
      improvements in health-promoting lifestyle choices and genomic knowledge specific
      to cardiovascular disease and type 2 diabetes suggested that the program may be
      effective in reducing risk. Feedback indicated the program was socioculturally
      acceptable and responsive to community needs. INTERPRETATION: These findings
      indicated that a tailored healthy lifestyle program integrating genomics and
      family history education was socioculturally appropriate and may feasibly be
      implemented to reduce cardiovascular disease and type 2 diabetes risk in a Latino
      community with limited health care resources. The project highlights
      contributions of community-based processes in tailoring interventions that are
      appropriate for community contexts.

PMID- 24286275
TI  - The effect of Philadelphia and Pennsylvania Clean Indoor Air Act on food services
      and drinking places sales and numbers, 1998-2011.
AB  - INTRODUCTION: Philadelphia enacted its Clean Indoor Air Act (CIAA) nearly 2 years
      before the statewide CIAA. In this study, we assessed the economic impact of
      CIAAs on 4 types of food services and drinking places and addressed the
      predominant limitation of previous pre-post ban studies, namely the lack of
      control for confounders and changes in secular trends over time. METHODS: We
      analyzed data from Pennsylvania Department of Revenue Quarterly 1998-2011 taxable
      county-level revenue sales and number of food services and drinking places.
      Region-specific and type-specific adjusted sales and number of food services and
      drinking places accounted for consumer spending as a general economic indicator.
      Segmented regression analysis of interrupted time-series methodology assessed
      changes in trend and level. RESULTS: Pennsylvania CIAA had no significant effect
      on adjusted sales or numbers except for an increase in sales in Philadelphia for
      limited-service eating places and in the surrounding 4 counties for special food
      services. Philadelphia CIAA was associated with an increase in adjusted numbers
      of full-service restaurants in Philadelphia and the rest of the state, special
      food services in Philadelphia, and drinking places in the rest of the state, and
      a decrease in the number of special food services in the surrounding counties.
      Philadelphia CIAA had no significant effect on adjusted sales except for an
      increase in special food services in the rest of the state. CONCLUSION: Overall,
      CIAAs had no negative business-related impact and, for the most part, suggest a
      positive impact on restaurant sales and numbers. Our results provide further
      support for comprehensive CIAA ordinance for restaurants.

PMID- 24286276
TI  - Identification of putative insulin-like peptides and components of insulin
      signaling pathways in parasitic platyhelminths by the use of genome-wide
      screening.
AB  - No endogenous insulin-like peptides in parasitic flatworms have been reported.
      Insulin receptors from flukes and tapeworms have been shown to interact directly
      with the host-derived insulin molecule, which suggests the exploitation of host
      derived insulin. In this study, a strategy of genome-wide searches followed by
      comprehensive analyses of strictly conserved features of the insulin family was
      used to demonstrate the presence of putative insulin-like peptides in the genomes
      of six tapeworms and two flukes. In addition, whole insulin signaling pathways
      were annotated on a genome-wide scale. Two putative insulin-like peptide genes in
      each genome of tapeworms and one insulin-like peptide gene in each genome of
      flukes were identified. The comprehensive analyses revealed that all of these
      peptides showed the common features shared by other members of the insulin
      family, and the phylogenetic analysis implied a putative gene duplication event
      in the Cestoda during the evolution of insulin-like peptide genes. The
      quantitative expression analysis and immunolocalization results suggested a
      putative role of these peptides in reproduction. Entire sets of major components
      of the classic insulin signaling pathway were successfully identified, suggesting
      that this pathway in parasitic flatworms might also regulate many other important
      biological activities. We believe that the identification of the insulin-like
      peptides gives us a better understanding of the insulin signaling pathway in
      these parasites, as well as host-parasite interactions.

PMID- 24286278
TI  - Human endogenous retroviruses and ADHD.
AB  - OBJECTIVES: Several lines of evidences suggest that human endogenous retroviruses
      (HERVs) are implicated in the development of many complex diseases with a
      multifactorial aetiology and a strong heritability, such as neurological and
      psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a
      neurodevelopmental disorder that results from a complex interaction of
      environmental, biological and genetic factors. Our aim was to analyse the
      expression levels of three HERV families (HERV-H, K and W) in patients with ADHD.
      METHODS: The expression of retroviral mRNAs from the three HERV families was
      evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with
      ADHD and 30 healthy controls by quantitative RT-PCR. RESULTS: The expression
      levels of HERV-H are significantly higher in patients with ADHD compared to
      healthy controls, while there are no differences in the expression levels of HERV
      K and W. CONCLUSIONS: Since the ADHD aetiology is due to a complex interaction of
      environmental, biological and genetic factors, HERVs may represent one link among
      these factors and clinical phenotype of ADHD. A future confirmation of HERV-H
      overexpression in a larger number of ADHD patients will make possible to identify
      it as a new parameter for this clinical condition, also contributing to deepen
      the study on the role of HERVs in the neurodevelopment diseases.

PMID- 24286279
TI  - Effects of dissolved water on Li+ solvation in 1-ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide ionic liquid studied by NMR.
AB  - (1)H and (7)Li NMR chemical shifts of 1-ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide-water solutions in the presence and absence of
      lithium bis(trifluoromethanesulfonyl)amide were determined at 293.2 K over a wide
      range of water concentrations from 0.0156 to 1.16 mol kg(-1). These results
      revealed the attractive interaction between water molecule and Li(+) as well as
      the hydrogen bonding among water molecules. Moreover, self-diffusion coefficients
      of water, 1-ethyl-3-methylimidazolium cation, Li(+), and
      bis(trifluoromethanesulfonyl)amide anion in the ionic liquid solutions at various
      water contents were determined by (1)H, (7)Li, and (19)F NMR techniques. It was
      found that Li(+) is averagely hydrated by eight water molecules in the ionic
      liquid solutions. Furthermore, (7)Li longitudinal relaxation times of Li(+) in
      the ionic liquid solutions at 293.2 K were measured with two different magnetic
      fields and various water contents. The mean one-jump distances of Li(+) in the
      ionic liquid solutions were estimated from the correlation times and the self
      diffusion coefficients. A comparison between the hydrodynamic radius and the mean
      one-jump distance of Li(+) suggested the formation of water channels in the ionic
      liquid solutions. 

PMID- 24286277
TI  - A bone substitute with high affinity for vitamin D-binding protein--relationship
      with niche of osteoclasts.
AB  - The biological activity of osteoblasts and osteoclasts is regulated not only by
      hormones but also by local growth factors, which are expressed in neighbouring
      cells or included in bone matrix. Previously, we developed hydroxyapatite (HA)
      composed of rod-shaped particles using applied hydrothermal methods (HHA), and it
      revealed mild biodegradability and potent osteoclast homing activity. Here, we
      compared serum proteins adsorbed to HHA with those adsorbed to conventional HA
      composed of globular-shaped particles (CHA). The two ceramics adsorbed serum
      albumin and gamma-globulin to similar extents, but affinity for gamma-globulin
      was much greater than that to serum albumin. The chemotactic activity for
      macrophages of serum proteins adsorbed to HHA was significantly higher than that
      of serum proteins adsorbed to CHA. Quantitative proteomic analysis of adsorbed
      serum proteins revealed preferential binding of vitamin D-binding protein (DBP)
      and complements C3 and C4B with HHA. When implanted with the femur of 8-week-old
      rats, HHA contained significantly larger amount of DBP than CHA. The biological
      activity of DBP was analysed and it was found that the chemotactic activity for
      macrophages was weak. However, DBP-macrophage activating factor, which is
      generated by the digestion of sugar chains of DBP, stimulated osteoclastogenesis.
      These results confirm that the microstructure of hydroxyapatite largely affects
      the affinity for serum proteins, and suggest that DBP preferentially adsorbed to
      HA composed of rod-shaped particles influences its potent osteoclast homing
      activity and local bone metabolism.

PMID- 24286280
TI  - Hsp60 chaperonopathies and chaperonotherapy: targets and agents.
AB  - INTRODUCTION: Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the
      co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also
      has other roles, including participation in pathogenic mechanisms. AREA COVERED:
      Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in
      which the chaperone plays a determinant etiologic-pathogenic role. These diseases
      justify selection of Hsp60 as a target for developing agents that interfere with
      its pathogenic effects. We provide information on how to proceed. EXPERT OPINION:
      The information available encourages the development of ways to improve Hsp60
      activity (positive chaperonotherapy) when deficient or to block it (negative
      chaperonotherapy) when pathogenic. Many questions are still unanswered and
      obstacles are obvious. More information is needed to establish when and why
      autologous Hsp60 becomes a pathogenic autoantigen, or induces cytokine formation
      and inflammation, or favors carcinogenesis. Clarification of these points will
      take considerable time. However, analysis of the Hsp60 molecule and a search for
      active compounds aimed at structural sites that will affect its functioning
      should continue without interruption. No doubt that some of these compounds will
      offer therapeutic hopes and will also be instrumental for dissecting structure
      function relationships at the biochemical and biological (using animal models and
      cultured cells) levels.

PMID- 24286281
TI  - Fungi: the neglected allergenic sources.
AB  - Allergic diseases are considered the epidemics of the twentieth century estimated
      to affect more than 30% of the population in industrialized countries with a
      still increasing incidence. During the past two decades, the application of
      molecular biology allowed cloning, production and characterization of hundreds of
      recombinant allergens. In turn, knowledge about molecular, chemical and
      biologically relevant allergens contributed to increase our understanding of the
      mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been
      largely demonstrated that fungi are potent sources of allergenic molecules
      covering a vast variety of molecular structures including enzymes, toxins, cell
      wall components and phylogenetically highly conserved cross-reactive proteins.
      Despite the large knowledge accumulated and the compelling evidence for an
      involvement of fungal allergens in the pathophysiology of allergic diseases,
      fungi as a prominent source of allergens are still largely neglected in basic
      research as well as in clinical practice. This review aims to highlight the
      impact of fungal allergens with focus on asthma and atopic dermatitis. 

PMID- 24286282
TI  - Evaluation of MRI T1-based treatment monitoring during laser-induced
      thermotherapy of liver metastases for necrotic size prediction.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of real-time magnetic
      resonance imaging (MRI) T1-based treatment monitoring for predicting volume of
      lesions induced by laser-induced thermotherapy (LITT) of liver metastases.
      MATERIALS AND METHODS: This prospective study was approved by the institutional
      review board and informed consent from all included patients was obtained. In 151
      patients, 237 liver metastases were ablated during 372 LITT procedures. 1.5 T MRI
      treatment monitoring was performed based on longitudinal relaxation time (T1)
      using fast low-angle shot (FLASH) sequences. Patients underwent additional
      contrast-enhanced MRI directly after LITT, 24 h after the procedure and during
      follow-up at 3, 6 and 12 months. The amount of energy necessary to induce a
      defined necrotic area was investigated within the various liver segments.
      RESULTS: The total amount of energy applied during LITT varied from 6.12-225.32
      kJ (mean 48.96 kJ). Ablation in liver segments 5 (2.12 kJ/cm(3)) and 8 (2.16
      kJ/cm(3)) required the highest energy. The overall pre-ablative metastasis volume
      ranged from 0.5-51.94 cm(3) (mean 1.99 cm(3), SD 25.49 cm(3)) while the volume
      measured in the last available T1 image varied from 0.78-120 cm(3) (mean 26.25
      cm(3), SD 25.66 cm(3)). Volumes measured via MRI T1-based treatment monitoring
      showed a stronger correlation with necrosis 24 h after LITT (r = 0.933, p <
      0.001) than contrast-enhanced MRI directly after the procedure (r = 0.888, p <
      0.001). CONCLUSIONS: Real-time MRI T1-based treatment monitoring during LITT of
      liver metastases allows for precise estimation of the resulting lesion volume and
      improves control of the energy necessary during ablation.

PMID- 24286283
TI  - Development of new devices for translumenal endoscopic esophageal anastomosis.
AB  - AIM: This study aimed to develop new devices for translumenal endoscopic
      esophageal anastomosis-a stent and a ligating device-and to confirm the
      feasibility of our novel procedure using those devices. MATERIALS AND METHODS: We
      designed a ligating device as an overtube whose tip worked like the EVL device
      (Sumitomo Bakelite Co. Ltd., Tokyo, Japan). The newly developed procedure for
      anastomosis is as follows: a silicone elastic band, which was released from the
      device located at the upper esophagus, and a custom-made expandable stent, which
      was expanded by the balloon catheter in the lower esophagus, tightened the upper
      and lower esophageal walls. After producing the devices, we performed the
      anastomosis procedure in porcine models. RESULTS: A ligating device and an
      expandable stent were developed for this study. An ex vivo feasibility study was
      performed in three porcine models. Endoscopic visualization revealed that all
      steps in this procedure were technically successful. The median time needed to
      perform this procedure was 24 (range, 19-25) minutes. Patency of the anastomosis
      was confirmed in all specimens. CONCLUSIONS: Translumenal esophagoesophageal
      anastomosis using the new devices was feasible. The procedure time was
      sufficiently short for clinical use. An in vivo survival study is needed to
      confirm the safety and reliability of this procedure.

PMID- 24286284
TI  - A single-blinded, randomized comparison of laparoscopic versus open bilateral
      hernia repair in boys.
AB  - AIM: The aim of this study is to determine whether laparoscopic repair (LR) of
      inguinal hernia is superior to open repair (OR) in bilateral cases. SUBJECTS AND
      METHODS: Sixty-two boys older than 6 years with bilateral hernias were included
      in our prospective, randomized, single-blinded clinical trial. All patients were
      administered morphine via patient-controlled analgesia for 24 hours. Pain scores
      were evaluated by the patients using a visual analog scale (VAS) at 1, 2, 4, 12,
      and 24 hours postoperatively. Operative time, pain scores, analgesic doses, and
      first mobilization attempt were evaluated. Parents also provided assessments of
      their children's recovery and wound appearance. RESULTS: Operative time was found
      to be slightly higher in OR compared with LR. VAS scores were higher in OR than
      in LR at 1 hour postoperatively (6.78 versus 3.88, respectively; P<.05). At the
      other times, VAS scores showed no significant differences. Although OR patients
      requested and delivered analgesics more frequently than LR patients, the
      difference was not significant. The scores given by parents for wound appearance
      were significantly higher in the bilateral LR group than in the bilateral OR
      group (89+/-4.23 and 78+/-6.7, respectively; P<.05). CONCLUSIONS: This trial
      demonstrates that LR in bilateral cases offers benefits compared with OR in terms
      of lower pain scores and analgesic requirements and of reduced operative and
      patient recovery times. However, the only significant difference was better wound
      cosmesis in bilateral LR cases.

PMID- 24286285
TI  - Phylogenetic and transcriptional analysis of an expanded bZIP transcription
      factor family in Phytophthora sojae.
AB  - BACKGROUND: Basic leucine zipper (bZIP) transcription factors are present
      exclusively in eukaryotes and constitute one of the largest and most diverse
      transcription factor families. The proteins are responsible for central
      developmental and physiological processes in plants, animals, and fungi,
      including the pathogenicity of fungal plant pathogens. However, there is limited
      understanding of bZIPs in oomycetes, which are fungus-like organisms in the
      kingdom Stramenopila. Oomycetes include many destructive plant pathogens,
      including the well-studied species Phytophthora sojae, which causes soybean stem
      and root rot. RESULTS: Candidate bZIPs encoded in the genomes of P. sojae and
      four other oomycetes, two diatoms, and two fungal species were predicted using
      bioinformatic methods. Comparative analysis revealed expanded numbers of bZIP
      candidates in oomycetes, especially the Phytophthora species, due to the
      expansion of several novel bZIP classes whose highly conserved asparagines in
      basic DNA-binding regions were substituted by other residues such as cysteine.
      The majority of these novel bZIP classes were mostly restricted to oomycetes. The
      large number of novel bZIPs appears to be the result of widespread gene
      duplications during oomycete evolution. The majority of P. sojae bZIP candidates,
      including both conventional and novel bZIP classes, were predicted to contain
      canonical protein secondary structures. Detection of gene transcripts using
      digital gene expression profiling and qRT-PCR suggested that most of the
      candidates were not pseudogenes. The major transcriptional shifts of bZIPs
      occurred during the zoosporangia/zoospore/cyst and host infection stages. Several
      infection-associated bZIP genes were identified that were positively regulated by
      H2O2 exposure. CONCLUSIONS: The identification of large classes of bZIP proteins
      in oomycetes with novel bZIP motif variants, that are conserved and
      developmentally regulated and thus presumably functional, extends our knowledge
      of this important family of eukaryotic transcription factors. It also lays the
      foundation for detailed studies of the roles of these proteins in development and
      infection in P. sojae and other oomycetes.

PMID- 24286287
TI  - Design, evaluation, and screening methods for efficient targeted mutagenesis with
      transcription activator-like effector nucleases in medaka.
AB  - Genome editing using engineered nucleases such as transcription activator-like
      effector nucleases (TALENs) has become a powerful technology for reverse
      genetics. In this study, we have described efficient detection methods for TALEN
      induced mutations at endogenous loci and presented guidelines of TALEN design for
      efficient targeted mutagenesis in medaka, Oryzias latipes. We performed a
      heteroduplex mobility assay (HMA) using an automated microchip electrophoresis
      system, which is a simple and high-throughput method for evaluation of in vivo
      activity of TALENs and for genotyping mutant fish of F1 or later generations. We
      found that a specific pattern of mutations is dominant for TALENs harboring
      several base pairs of homologous sequences in target sequence. Furthermore, we
      found that a 5' T, upstream of each TALEN-binding sequence, is not essential for
      genomic DNA cleavage. Our findings provide information that expands the potential
      of TALENs and other engineered nucleases as tools for targeted genome editing in
      a wide range of organisms, including medaka. 

PMID- 24286286
TI  - A controlled trial to determine the efficacy of red and near-infrared light
      treatment in patient satisfaction, reduction of fine lines, wrinkles, skin
      roughness, and intradermal collagen density increase.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety and efficacy
      of two novel light sources for large area and full body application, providing
      polychromatic, non-thermal photobiomodulation (PBM) for improving skin feeling
      and appearance. BACKGROUND DATA: For non-thermal photorejuvenation, laser and LED
      light sources have been demonstrated to be safe and effective. However, lasers
      and LEDs may offer some disadvantages because of dot-shaped (punctiform) emission
      characteristics and their narrow spectral bandwidths. Because the action spectra
      for tissue regeneration and repair consist of more than one wavelength, we
      investigated if it is favorable to apply a polychromatic spectrum covering a
      broader spectral region for skin rejuvenation and repair. MATERIALS AND METHODS:
      A total of 136 volunteers participated in this prospective, randomized, and
      controlled study. Of these volunteers, 113 subjects randomly assigned into four
      treatment groups were treated twice a week with either 611-650 or 570-850 nm
      polychromatic light (normalized to ~ 9 J/cm(2) in the range of 611-650 nm) and
      were compared with controls (n=23). Irradiances and treatment durations varied in
      all treatment groups. The data collected at baseline and after 30 sessions
      included blinded evaluations of clinical photography, ultrasonographic collagen
      density measurements, computerized digital profilometry, and an assessment of
      patient satisfaction. RESULTS: The treated subjects experienced significantly
      improved skin complexion and skin feeling, profilometrically assessed skin
      roughness, and ultrasonographically measured collagen density. The blinded
      clinical evaluation of photographs confirmed significant improvement in the
      intervention groups compared with the control. CONCLUSIONS: Broadband
      polychromatic PBM showed no advantage over the red-light-only spectrum. However,
      both novel light sources that have not been previously used for PBM have
      demonstrated efficacy and safety for skin rejuvenation and intradermal collagen
      increase when compared with controls.

PMID- 24286288
TI  - The use of a co-design model in improving timely bleed reporting by adults with
      haemophilia living in the Auckland region of New Zealand.
AB  - Many adult patients diagnosed with phenotypically moderate and severe haemophilia
      living in the Auckland region of New Zealand do not report bleeding episodes
      within a timeframe that allows for optimal assessment and management. This can
      result in poor clinical outcomes for patients and poor oversight of the use of
      expensive clotting factor concentrates. Our goal was to improve both the number
      and speed at which bleeding episodes were reported to our centre, improving
      access to care and clinical oversight of the use of expensive factor concentrates
      and aiding the development of a care partnership with patients. We worked with 70
      adult PWH living in the Auckland region of New Zealand with moderate and severe
      haemophilia A and B. Over a 5-month period between March and July 2013 we used a
      co-design model to develop and implement a range of strategies to improve the
      timing and frequency of bleed reporting. Mean bleed reporting time was reduced
      threefold, with a threefold increase in the number of bleeds reported per month.
      We reduced the number of bleeding episodes reported outside of a prespecified 48
      h time limit by 68%. We significantly improved bleed reporting and time to
      report, indicating improved access to our services, improved clinical oversight
      and improved accountability to our national funder. We have achieved a care
      partnership and a reduction in factor consumption for the study population
      without compromising the quality of care they receive. 

PMID- 24286289
TI  - Transcriptomic profiles of Heterobasidion annosum under abiotic stresses and
      during saprotrophic growth in bark, sapwood and heartwood.
AB  - The success of many wood decaying fungi lies in their ability to overcome
      unfavourable environmental conditions within and outside of litter and wood
      debris. Although so much has been learned about the ecology, taxonomy and
      physiology of several wood decaying basidiomycete fungi, the molecular basis for
      their survival in a diverse range of substrates and ecological habitats has been
      very little studied. Using the wood decay fungus (Heterobasidion annosum s.s.) as
      a model, we investigated its transcriptomic response when exposed to several
      environmental stressors (high and low temperature, osmotic stress, oxidative
      stress and nutrient starvation) and during growth on specific pine wood
      compartments (bark, sapwood and heartwood). Among other genes and pathways, we
      documented the specific induction of the major facilitator superfamily 1 and
      cytochrome P450 families at low temperature, and protein kinases together with
      transcription factors during starvation. On the other hand, during saprotrophic
      growth, we observed the induction of many glycosyl hydrolases, three multi-copper
      oxidases (MCO), five manganese peroxidases (MnP) and one oxidoreductase which are
      specific for wood degradation. This is the first study providing insights on the
      potential mechanisms for adaptation to abiotic stresses and pine heartwood
      degradation in H. annosum s.s. 

PMID- 24286290
TI  - An assessment of change in risk perception and optimistic bias for hurricanes
      among Gulf Coast residents.
AB  - This study focuses on levels of concern for hurricanes among individuals living
      along the Gulf Coast during the quiescent two-year period following the
      exceptionally destructive 2005 hurricane season. A small study of risk perception
      and optimistic bias was conducted immediately following Hurricanes Katrina and
      Rita. Two years later, a follow-up was done in which respondents were
      recontacted. This provided an opportunity to examine changes, and potential
      causal ordering, in risk perception and optimistic bias. The analysis uses 201
      panel respondents who were matched across the two mail surveys. Measures included
      hurricane risk perception, optimistic bias for hurricane evacuation, past
      hurricane experience, and a small set of demographic variables (age, sex, income,
      and education). Paired t-tests were used to compare scores across time. Hurricane
      risk perception declined and optimistic bias increased. Cross-lagged correlations
      were used to test the potential causal ordering between risk perception and
      optimistic bias, with a weak effect suggesting the former affects the latter.
      Additional cross-lagged analysis using structural equation modeling was used to
      look more closely at the components of optimistic bias (risk to self vs. risk to
      others). A significant and stronger potentially causal effect from risk
      perception to optimistic bias was found. Analysis of the experience and
      demographic variables' effects on risk perception and optimistic bias, and their
      change, provided mixed results. The lessening of risk perception and increase in
      optimistic bias over the period of quiescence suggest that risk communicators and
      emergency managers should direct attention toward reversing these trends to
      increase disaster preparedness. 

PMID- 24286291
TI  - A scientific sequel to Stieg Larsson: relationship between Pandemrix--pandemic
      influenza vaccine--and the subsequent development of narcolepsy.

PMID- 24286292
TI  - Genome-wide expressional and functional analysis of calcium transport elements
      during abiotic stress and development in rice.
AB  - Ca2+ homeostasis is required to maintain a delicate balance of cytosolic Ca2+
      during normal and adverse growth conditions. Various Ca2+ transporters actively
      participate to maintain this delicate balance especially during abiotic stresses
      and developmental events in plants. In this study, we present a genome-wide
      account, detailing expression profiles, subcellular localization and functional
      analysis of rice Ca2+ transport elements. Exhaustive in silico data mining and
      analysis resulted in the identification of 81 Ca2+ transport element genes, which
      belong to various groups such as Ca2+-ATPases (pumps), exchangers, channels,
      glutamate receptor homologs and annexins. Phylogenetic analysis revealed that
      different Ca2+ transporters are evolutionarily conserved across different plant
      species. Comprehensive expression analysis by gene chip microarray and
      quantitative RT-PCR revealed that a substantial proportion of Ca2+ transporter
      genes were expressed differentially under abiotic stresses (salt, cold and
      drought) and reproductive developmental stages (panicle and seed) in rice. These
      findings suggest a possible role of rice Ca2+ transporters in abiotic stress and
      development triggered signaling pathways. Subcellular localization of Ca2+
      transporters from different groups in Nicotiana benthamiana revealed their
      variable localization to different compartments, which could be their possible
      sites of action. Complementation of Ca2+ transport activity of K616 yeast mutant
      by Ca2+-ATPase OsACA7 and involvement in salt tolerance verified its functional
      behavior. This study will encourage detailed characterization of potential
      candidate Ca2+ transporters for their functional role in planta.

PMID- 24286293
TI  - Can alcohol consumption be an alternative treatment for fibromyalgia?
AB  - Treatment of chronic pain conditions such as fibromyalgia is challenging due to
      limitations of drug therapies. An initial exploration into the relationships
      between self-reported alcohol consumption, symptom severity, and quality of life
      for individuals with fibromyalgia sheds new light on plausible hypotheses and
      potential mechanisms of action for future research. Evidence suggests that
      alcohol consumption may improve social and psychological factors because of
      activity in the ascending and descending pain pathways in modulating gamma
      aminobutyric acid neurotransmission. Further methodologically rigorous studies in
      this field to improve well-being of individuals with fibromyalgia are warranted.

PMID- 24286294
TI  - Unusual cause of syncope in a patient with ischemic heart disease.
AB  - Lithium is a commonly used drug for bipolar mood disorder. Though effective, it
      has a narrow therapeutic range and has potentially life-threatening effects at
      higher serum levels. Lithium toxicity can be precipitated by several drug
      interactions. Many commonly used cardiac drugs have serious drug interaction with
      lithium which is not commonly known in clinical practice. We present a case where
      a patient on lithium therapy since 15 years, presented with sinus arrest and
      syncope due to lithium toxicity, within 2 weeks of initiation of low dose
      angiotensin converting enzyme (ACE) inhibitor. The patient however needed
      temporary pacemaker support and had an uneventful recovery, without the need for
      a permanent pacemaker, once the lithium levels fell down to normal. 

PMID- 24286295
TI  - Decreased whole-blood global DNA methylation is related to serum hormones in
      anorexia nervosa adolescents.
AB  - OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine
      cycle, governs the dynamics of DNA methylation, epigenetically regulating gene
      expression, and has been reported altered in anorexia nervosa (AN) adult
      patients. The aim of this study consisted in assessing whole-blood DNA
      methylation in adolescent AN patients, assessing its significance in relationship
      to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation
      was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent
      females affected by restrictive type AN and compared to 13 healthy controls.
      Homocysteine, vitamin B12 and folate plasma levels were assessed as well as
      fasting plasma levels of leptin and steroid hormones. Clinical variables,
      including severity and associate states and traits, were assessed by means of the
      EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA
      methylation is modestly albeit significantly reduced in AN adolescents with
      respect to controls, correlating with plasma leptin and steroid hormone levels.
      Conversely, clinical traits did not correlate with the outcome variable.
      CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN
      pathology or vulnerability might lead to develop useful markers for diagnosis,
      prognostic classification and tailored therapeutic interventions in these
      vulnerable patients since the earliest phases of their disease.

PMID- 24286297
TI  - The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima
      media thickness in patients with rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a complex polygenic disease associated
      with chronic inflammation, accelerated atherosclerosis and increased
      cardiovascular (CV) mortality. A recent meta-analysis has described the ZC3HC1
      rs11556924 polymorphism as one of the most important signals associated with
      coronary artery disease (CAD) in non-rheumatic Caucasian individuals. In this
      study we evaluated the potential association of this gene polymorphism with
      subclinical atherosclerosis assessed by the evaluation of carotid intima-media
      thickness (cIMT) in RA patients. METHODS: This study included 502 RA patients
      from Northern Spain. The ZC3HC1 rs11556924 polymorphism was genotyped with TaqMan
      single-nucleotide polymorphism (SNP) genotyping assays (C__31283062_10) in a
      7900HT real-time polymerase chain reaction (PCR) system. cIMT was also assessed
      in these patients by carotid ultrasonography (US) technology. RESULTS: RA
      patients carrying the TT genotype had significantly higher cIMT values than those
      homozygous for the CC genotype (mean +/- standard deviation (SD): 0.76 +/- 0.18
      mm and mean +/- SD: 0.71 +/- 0.16 mm respectively; P = 0.03) even after adjusting
      the results for sex, age at the time of US study, follow-up time and traditional
      CV risk factors (P = 0.04) evidencing that the effect conferred by ZC3HC1
      rs11556924 polymorphism is independent of the traditional CV risk factors.
      CONCLUSION: Our results indicate that ZC3HC1 rs11556924 polymorphism is
      associated with subclinical atherosclerosis in RA.

PMID- 24286298
TI  - Refined OPLS all-atom force field parameters for n-pentadecane, methyl acetate,
      and dimethyl phosphate.
AB  - OPLS All-Atom (OPLS/AA) is a generic all-atom force field which was fine-tuned to
      accurately reproduce condensed phase properties of organic liquids. Its
      application in modeling of lipid membranes is, however, limited mainly due to the
      inability to correctly describe phase behavior and organization of the
      hydrophobic core of the model lipid bilayers. Here we report new OPLS/AA
      parameters for n-pentadecane, methyl acetate, and dimethyl phosphate anion. For
      the new force field parameters, we show very good agreement between calculated
      and numerous reference data, including liquid density, enthalpy of vaporization,
      free energy of hydration, and selected transport properties. The new OPLS/AA
      parameters have been used in successful submicrosecond MD simulations of bilayers
      made of bacterial glycolipids whose results will be published elsewhere shortly. 

PMID- 24286296
TI  - Efficacy and safety of rituximab treatment in early primary Sjogren's syndrome: a
      prospective, multi-center, follow-up study.
AB  - INTRODUCTION: Primary Sjogren's syndrome (pSS) is an autoimmune disorder
      affecting exocrine glands; however, a subgroup of pSS patients experience
      systemic extra-glandular involvement leading to a worsening of disease prognosis.
      Current therapeutic options are mainly empiric and often translated by other
      autoimmune diseases. In the last few years growing evidence suggests that B-cell
      depletion by rituximab (RTX) is effective also in pSS. Patients with early active
      disease appear to be those who could benefit the most from RTX. The aim of this
      study was to investigate the efficacy and safety of RTX in comparison to disease
      modifying anti-rheumatic drugs (DMARDs) in early active pSS patients. METHODS:
      Forty-one patients with early pSS and active disease (EULAR Sjogren's syndrome
      disease activity index, ESSDAI >= 6) were enrolled in the study. Patients were
      treated with either RTX or DMARDs in two different Rheumatology centers and
      followed up for 120 weeks. Clinical assessment was performed by ESSDAI every 12
      weeks up to week 120 and by self-reported global disease activity pain, sicca
      symptoms and fatigue on visual analogic scales, unstimulated saliva flow and
      Schirmer's I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was
      performed every 12 weeks to week 120. Two labial minor salivary gland (MSG)
      biopsies were obtained from all patients at the time of inclusion in the study
      and at week 120. RESULTS: Our study demonstrated that RTX treatment results in a
      faster and more pronounced decrease of ESSDAI and other clinical parameters
      compared to DMARDs treatment. No adverse events were reported in the two groups.
      We also observed that RTX is able to reduce glandular infiltrate, interfere with
      B/T compartmentalization and consequently with the formation of ectopic lymphoid
      structures and germinal center-like structures in pSS-MSGs. CONCLUSIONS: To our
      knowledge, this is the first study performed in a large cohort of early active
      pSS patients for a period of 120 weeks. We showed that RTX is a safe and
      effective agent to be employed in pSS patients with systemic, extra-glandular
      involvement. Furthermore, our data on pSS-MSGs provide additional biological
      basis to employ RTX in this disease.

PMID- 24286300
TI  - Adolescent family perceptions in the At-Risk Mental State for psychosis.
AB  - AIM: There is a long-standing interest in the relationship between patients
      affected by psychosis and their families. Previous research also suggests that
      perceived family dysfunction is a factor commonly associated with psychological
      problems in adolescence. The current study examined the role of self-reported
      family perceptions in the context of adolescents with an At-Risk Mental State
      (ARMS) for psychosis. METHODS: Family perceptions were obtained using the Family
      Perceptions Scale (FPS) and compared across three groups; an ARMS for psychosis
      group (n = 44), a first-episode affective/non-affective psychosis group (n = 26)
      and a control group (n = 140) drawn from a community population. RESULTS: Scores
      on the FPS Expressed Emotion subscale were significantly higher in the psychosis
      and ARMS groups, compared to controls (P = 0.039 and P = 0.041, respectively). In
      contrast, participants in the ARMS group reported poorer perceived problem
      solving and lower levels of nurturing behaviour in their families compared to
      controls (P = 0.032 and P = 0.027). Overall, family perceptions were not related
      to symptom severity in both the ARMS and psychosis groups (except for manic
      symptomatology and Expressed Emotion). CONCLUSIONS: These findings highlight that
      ARMS patients are likely to report higher levels of perceived family dysfunction
      compared to a community sample of young people. However, the mechanisms by which
      family perceptions may contribute to the development of distressing psychotic
      symptoms remain unclear and require further study. Family work, with a focus upon
      improving perceived expressed emotion, nurturing behaviours and hostility may at
      this stage represent a feasible adjunct therapy for those with ARMS.

PMID- 24286301
TI  - Escherichia coli O26 in feedlot cattle: fecal prevalence, isolation,
      characterization, and effects of an E. coli O157 vaccine and a direct-fed
      microbial.
AB  - Escherichia coli O26 is second only to O157 in causing foodborne, Shiga toxin
      producing E. coli (STEC) infections. Our objectives were to determine fecal
      prevalence and characteristics of E. coli O26 in commercial feedlot cattle
      (17,148) that were enrolled in a study to evaluate an E. coli O157:H7 siderophore
      receptor and porin (SRP((r))) vaccine (VAC) and a direct-fed microbial (DFM;
      10(6) colony-forming units [CFU]/animal/day of Lactobacillus acidophilus and
      10(9) CFU/animal/day of Propionibacterium freudenreichii). Cattle were randomly
      allocated to 40 pens within 10 complete blocks; pens were randomly assigned to
      control, VAC, DFM, or VAC+DFM treatments. Vaccine was administered on days 0 and
      21, and DFM was fed throughout the study. Pen-floor fecal samples (30/pen) were
      collected weekly for the last 4 study weeks. Samples were enriched in E. coli
      broth and subjected to a multiplex polymerase chain reaction (PCR) designed to
      detect O26-specific wzx gene and four major virulence genes (stx1, stx2, eae, and
      ehxA) and to a culture-based procedure that involved immunomagnetic separation
      and plating on MacConkey agar. Ten presumptive E. coli colonies were randomly
      picked, pooled, and tested by the multiplex PCR. Pooled colonies positive for O26
      serogroup were streaked on sorbose MacConkey agar, and 10 randomly picked
      colonies per sample were tested individually by the multiplex PCR. The overall
      prevalence of E. coli O26 was higher (p<0.001) by the culture-based method
      compared to the PCR assay (22.7 versus 10.5%). The interventions (VAC and or DFM)
      had no impact on fecal shedding of O26. Serogroup O26 was recovered in pure
      culture from 23.9% (260 of 1089) of O26 PCR-positive pooled colonies. Only 7 of
      the 260 isolates were positive for the stx gene and 90.1% of the isolates
      possessed an eaebeta gene that codes for intimin subtype beta, but not the bfpA
      gene, which codes for bundle-forming pilus. Therefore, the majority of the O26
      recovered from feedlot cattle feces was atypical enteropathogenic E. coli, and
      not STEC.

PMID- 24286299
TI  - Myeloid related protein induces muscle derived inflammatory mediators in juvenile
      dermatomyositis.
AB  - INTRODUCTION: The aetiopathogenesis of juvenile dermatomyositis (JDM) remains
      poorly understood. In particular the contribution of monocytes or macrophages,
      which are frequently observed to be an infiltrate within muscle tissue very early
      in the disease process, is unknown. We hypothesised that these cells secrete the
      pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to
      muscle pathology in JDM. METHODS: In this study of 56 JDM patients, serum MRP8/14
      levels were compared with clinical measures of disease activity. Muscle biopsies
      taken early in disease were assessed by immunohistochemistry to determine the
      frequency and identity of MRP-expressing cells. The effects of MRP stimulation
      and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or
      supernatant levels of cytokines were analyzed by multiplex immunoassay. RESULTS:
      Serum MRP8/14 correlated with physician's global assessment of disease activity
      in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis
      assessment score (CMAS, R = -0.55, p = 0.004). MRP8/14 was widely expressed by
      CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8
      led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both
      inflammatory mediators were detected in significantly higher levels in the serum
      of JDM patients compared to healthy controls. CONCLUSIONS: This study is the
      first to identify serum MRP8/14 as a potential biomarker for disease activity in
      JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may
      contribute to myositis, by driving the local production of cytokines directly
      from muscle.

PMID- 24286302
TI  - Reduced dream-recall frequency in left-handed adolescents: a replication.
AB  - The ability to recall a dream upon waking up in the morning has been linked to a
      broad variety of factors such as personality, creativity, sleep behaviour and
      cognitive function. There have been conflicting findings as to whether dream
      recall is related more to the right or to the left hemisphere, and conflicting
      findings regarding the relationship of dream-recall frequency to handedness. We
      have found previously that right- and mixed-handers report having more dreams
      than left-handers, a finding more pronounced among adolescents than adults. In
      the present sample of 3535 participants aged from 6 to 18 years, right-handedness
      and mixed/inconsistent handedness were associated with higher dream-recall
      frequency compared to that of left-handed persons, again especially in
      adolescents compared with children. Further research is required to uncover the
      reason for the lower frequency of dream recall by left-handers. 

PMID- 24286304
TI  - Akt pathway protein expression in gastrointestinal Kaposi sarcomas: relevance for
      tumor biology.
AB  - Gastrointestinal Kaposi sarcoma (KS) is classical, but rare. The AKT signaling
      pathway plays a central role in G protein-coupled receptor, key protein of KS
      histogenesis, encoded by KSHV/HHV8. There is increasing evidence that rapamycin,
      acting on AKT pathway, may be useful in the treatment of KS, including in HIV
      patients. We aimed to study the expression pattern of AKT pathway proteins in
      gastrointestinal KS. Expression of AKT, 4EBP1, PTEN, mTOR was assessed in 19
      gastrointestinal KS biopsies by immunohistochemistry (17 patients). Protein
      expression in tumor spindle cells and in intratumor stromal vascular endothelial
      cells was analyzed with regard to clinicomorphological features. Tumor AKT
      related to lack of marked extravasated erythrocytes, tumor PTEN to presence of
      intratumor hemosiderin (p = 0.04 for both comparisons). Presence of both
      extravasated erythrocytes and hemosiderin related directly to endothelial stromal
      vascular nuclear PTEN and to low endothelial mTOR (p = 0.4 and 0.03,
      respectively). High tumor 4EBP1 related to a high slit-type abnormal vascular
      component (p = 0.04). The results of our study suggest pro-permeability or pro
      angiogenic roles for 4EBP1 and PTEN and, opposite roles for AKT and mTOR in KS.
      Our hypotheses warrant further studies to obtain more generally applicable
      results.

PMID- 24286305
TI  - Exploring grape marc as trove for new thermotolerant and inhibitor-tolerant
      Saccharomyces cerevisiae strains for second-generation bioethanol production.
AB  - BACKGROUND: Robust yeasts with high inhibitor, temperature, and osmotic tolerance
      remain a crucial requirement for the sustainable production of lignocellulosic
      bioethanol. These stress factors are known to severely hinder culture growth and
      fermentation performance. RESULTS: Grape marc was selected as an extreme
      environment to search for innately robust yeasts because of its limited
      nutrients, exposure to solar radiation, temperature fluctuations, weak acid and
      ethanol content. Forty newly isolated Saccharomyces cerevisiae strains gave high
      ethanol yields at 40 degrees C when inoculated in minimal media at high sugar
      concentrations of up to 200 g/l glucose. In addition, the isolates displayed
      distinct inhibitor tolerance in defined broth supplemented with increasing levels
      of single inhibitors or with a cocktail containing several inhibitory compounds.
      Both the fermentation ability and inhibitor resistance of these strains were
      greater than those of established industrial and commercial S. cerevisiae yeasts
      used as control strains in this study. Liquor from steam-pretreated sugarcane
      bagasse was used as a key selective condition during the isolation of robust
      yeasts for industrial ethanol production, thus simulating the industrial
      environment. The isolate Fm17 produced the highest ethanol concentration (43.4
      g/l) from the hydrolysate, despite relatively high concentrations of weak acids,
      furans, and phenolics. This strain also exhibited a significantly greater
      conversion rate of inhibitory furaldehydes compared with the reference strain S.
      cerevisiae 27P. To our knowledge, this is the first report describing a strain of
      S. cerevisiae able to produce an ethanol yield equal to 89% of theoretical
      maximum yield in the presence of high concentrations of inhibitors from sugarcane
      bagasse. CONCLUSIONS: This study showed that yeasts with high tolerance to
      multiple stress factors can be obtained from unconventional ecological niches.
      Grape marc appeared to be an unexplored and promising substrate for the isolation
      of S. cerevisiae strains showing enhanced inhibitor, temperature, and osmotic
      tolerance compared with established industrial strains. This integrated approach
      of selecting multiple resistant yeasts from a single source demonstrates the
      potential of obtaining yeasts that are able to withstand a number of fermentation
      related stresses. The yeast strains isolated and selected in this study represent
      strong candidates for bioethanol production from lignocellulosic hydrolysates.

PMID- 24286303
TI  - Unbalanced distribution of materials: the art of giving rise to hepatocytes from
      liver stem/progenitor cells.
AB  - Liver stem/progenitor cells (LSPCs) are able to duplicate themselves and
      differentiate into each type of cells in the liver, including mature hepatocytes
      and cholangiocytes. Understanding how to accurately control the hepatic
      differentiation of LSPCs is a challenge in many fields from preclinical to
      clinical treatments. This review summarizes the recent advances made to control
      the hepatic differentiation of LSPCs over the last few decades. The hepatic
      differentiation of LSPCs is a gradual process consisting of three main steps:
      initiation, progression and accomplishment. The unbalanced distribution of the
      affecting materials in each step results in the hepatic maturation of LSPCs. As
      the innovative and creative works for generating hepatocytes with full functions
      from LSPCs are gradually accumulated, LSPC therapies will soon be a new choice
      for treating liver diseases.

PMID- 24286306
TI  - Plant homeodomain finger protein 11 promotes class switch recombination to IgE in
      murine activated B cells.
AB  - BACKGROUND: Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are
      strongly associated with high serum IgE levels and clinical severity of atopic
      patients. However, the precise mechanism has not been fully elucidated. We
      investigated the role of Phf11 in class switch recombination (CSR) to IgE by
      activated B cells. METHODS: We generated Phf11 transgenic (Lckd-Phf11-Tg) mice
      that express the exogenous murine Phf11 in lymphocytes under the control of
      distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11
      Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and
      nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic
      rhinitis model. RESULTS: The exogenous Phf11 promoted CSR to IgG1 and IgE in
      activated B cells with an increase in germ line transcript (GLT) gamma1 and GLT
      epsilon expression. The exogenous Phf11 augmented transcriptional activity of the
      GLT gamma1 and GLT epsilon promoters through permissive histone modifications and
      binding of NF-kappaB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT
      epsilon promoter with increased binding of NF-kappaB. Silencing of the endogenous
      Phf11 reduced the frequency of CSR to IgE and GLT epsilon expression, but not to
      IgG1 or GLT gamma1 expression, in activated B cells. In an allergic rhinitis
      model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA
      specific IgE and the frequency of nose scratching. CONCLUSION: Phf11 accelerates
      CSR to IgE in activated B cells by increasing the transcriptional activity of GLT
      epsilon promoter and contributes to the exacerbation of allergic responses. These
      findings provide a novel therapeutic target for allergic diseases.

PMID- 24286307
TI  - Cardiovascular comorbidities are increased in U.S. patients with haemophilia A: a
      retrospective database analysis.
AB  - There is conflicting evidence in the literature on whether individuals with
      haemophilia in the USA have greater, reduced, or similar risks for cardiovascular
      disease as the general population. This study evaluated the prevalence of
      cardiovascular comorbidities among USA males with haemophilia A, relative to an
      unaffected general male population with similar characteristics. Males with
      haemophilia A and continuous insurance coverage were identified by ICD-9-CM code
      286.0 (1 January 2007-31 December 2009) using the MarketScan Commercial and
      Medicare Research Databases. Individuals with haemophilia A were exact matched
      1:3 with males without a diagnosis of haemophilia A. The prevalence of
      cardiovascular comorbidities identified by ICD-9-CM code was determined for
      matched cohorts. Of the study population, 2506 were grouped in the haemophilia A
      cohort and 7518 in the general cohort. Proportions of individuals with
      haemorrhagic stroke (2.0% vs. 0.5%, P < 0.001), ischemic stroke (4.7% vs. 2.7%, P
      < 0.001), coronary artery disease (10.7% vs. 5.8%, P < 0.001), myocardial
      infarction (0.8% vs. 0.3%, P = 0.003), hypertension (22.6% vs. 15.5%, P < 0.001),
      hyperlipidaemia (15.9% vs. 11.9%, P < 0.001), arterial thrombosis (12.1% vs.
      5.9%, P < 0.001), and venous thrombosis (4.4% vs. 1.1%, P < 0.001) were
      significantly greater for the haemophilia A cohort. Results were consistent
      across most age groups, and comorbidities appeared at an earlier age in those
      with haemophilia A than in the general population. Among the USA haemophilia A
      population cardiovascular comorbidities are more prevalent and they appear
      earlier in life in comparison to the general male population, suggesting the need
      for earlier, enhanced screening for age-related comorbidities in the haemophilia
      community.

PMID- 24286308
TI  - HDAC3 acts as a negative regulator of angiogenesis.
AB  - Histone deacetylase-3 (HDAC3) is involved in cellular proliferation, apoptosis
      and transcriptional repression. However, the role of HDAC3 in angiogenesis
      remains unknown. HDAC3 negatively regulated the expression of angiogenic factors,
      such as VEGF and plasminogen activator inhibitor-1 (PAI-1). HDAC3 showed binding
      to promoter sequences of PAI-1. HDAC3 activity was necessary for the expression
      regulation of PAI-1 by HDAC3. VEGF decreased the expression of HDAC3, and the
      down-regulation of HDAC3 enhanced endothelial cell tube formation. HDAC3
      negatively regulated tumor-induced angiogenic potential. We show the novel role
      of HDAC3 as a negative regulator of angiogenesis.

PMID- 24286309
TI  - WITHDRAWN: Selenite induces apoptosis in colorectal cancer cells through
      interaction with thioredoxin reductase.
AB  - Ahead of Print article withdrawn by publisher. The chemopreventive and
      chemotherapeutic effects of selenium compounds has been well validated in
      colorectal cancer by epidemiologic and pre-clinical studies, but the underlying
      mechanisms still remains elusive. We provide evidence that interaction between
      selenium metabolites and selenoproteins participates in colorectal cancer
      suppression induced by selenite. We found that supranutritional doses of selenite
      could induces inhibition of thioredoxin system and apoptosis in SW480 cells, and
      cause direct modifications of thiol groups on TrxR protein. Moreover, we showed
      that TrxR ablation sensitized apoptosis induced by selenite, and the synergistic
      effect was related to Bax activation and mitochondrial apoptotic pathway. Our
      results proposed that TrxR is an important target for selenite in colorectal
      cancer suppression, and selenite in combination with TrxR inhibition could be an
      effective strategy to treat colorectal cancer.

PMID- 24286310
TI  - Enhancement of UVB radiation-mediated apoptosis by knockdown of cytosolic NADP+
      dependent isocitrate dehydrogenase in HaCaT cells.
AB  - Ultraviolet B (UVB) radiation induces the production of reactive oxygen species
      (ROS) that promote apoptotic cell death. We showed that cytosolic NADP+-dependent
      isocitrate dehydrogenase (IDPc) plays an essential role in the control of
      cellular redox balance and defense against oxidative damage, by supplying NADPH
      for antioxidant systems. In this study, we demonstrated that knockdown of IDPc
      expression by RNA interference enhances UVB-induced apoptosis of immortalized
      human HaCaT keratinocytes. This effect manifested as DNA fragmentation, changes
      in cellular redox status, mitochondrial dysfunction, and modulation of apoptotic
      marker expression. Based on our findings, we suggest that attenuation of IDPc
      expression may protect skin from UVB-mediated damage, by inducing the apoptosis
      of UV-damaged cells.

PMID- 24286311
TI  - Therapeutic effect of a TM4SF5-specific peptide vaccine against colon cancer in a
      mouse model.
AB  - Molecular-targeted therapy has gained attention because of its high efficacy and
      weak side effects. Previously, we confirmed that transmembrane 4 superfamily
      member 5 protein (TM4SF5) can serve as a molecular target to prevent or treat
      hepatocellular carcinoma (HCC). We recently extended the application of the
      peptide vaccine, composed of CpG-DNA, liposome complex, and TM4SF5 peptide, to
      prevent colon cancer in a mouse model. Here, we first implanted mice with mouse
      colon cancer cells and then checked therapeutic effects of the vaccine against
      tumor growth. Immunization with the peptide vaccine resulted in robust production
      of TM4SF5-specific antibodies, alleviated tumor growth, and reduced survival rate
      of the tumor-bearing mice. We also found that serum levels of VEGF were markedly
      reduced in the mice immunized with the peptide vaccine. Therefore, we suggest
      that the TM4SF5-specific peptide vaccine has a therapeutic effect against colon
      cancer in a mouse model.

PMID- 24286312
TI  - Nutlin-3 downregulates p53 phosphorylation on serine392 and induces apoptosis in
      hepatocellular carcinoma cells.
AB  - Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical
      application for the human hepatocellular carcinoma (HCC) treatment. The
      reactivation of p53 is an attractive therapeutic strategy in cancer with
      disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in
      various cancers. The post-translational modifications of p53 are a hot topic, but
      there are some controversy ideas about the function of phospho-Ser392-p53 protein
      in cancer cell lines in response to Nutlin-3. Therefore, we investigated the
      relationship between Nutlin-3 and phospho-Ser392-p53 protein expression levels in
      SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that
      Nutlin-3 induced apoptosis through down-regulation phospho-Ser392-p53 in two HCC
      cells. The result suggests that inhibition of p53 phosphorylation on Ser392
      presents an alternative for HCC chemotherapy.

PMID- 24286313
TI  - Establishment and characterization of bortezomib-resistant U266 cell line:
      constitutive activation of NF-kappaB-mediated cell signals and/or alterations of
      ubiquitylation-related genes reduce bortezomib-induced apoptosis.
AB  - Bortezomib has been known as the most promising anti-cancer drug for multiple
      myeloma (MM). However, recent studies reported that not all MM patients respond
      to bortezomib. To overcome such a stumbling-block, studies are needed to clarify
      the mechanisms of bortezomib resistance. In this study, we established a
      bortezomib-resistant cell line (U266/velR), and explored its biological
      characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also
      showed crossresistance to the chemically unrelated drug thalidomide. U266/velR
      cells had a higher proportion of CD138 negative subpopulation, known as stem-like
      feature, compared to parental U266 cells. U266/velR showed relatively less
      inhibitory effect of prosurvival NF-kappaB signaling by bortezomib. Further
      analysis of RNA microarray identified genes related to ubiquitination that were
      differentially regulated in U266/velR. Moreover, the expression level of CD52 in
      U266 cells was associated with bortezomib response. Our findings provide the
      basis for developing therapeutic strategies in bortezomib-resistant relapsed and
      refractory MM patients.

PMID- 24286314
TI  - Characterization of a novel posttranslational modification in polypyrimidine
      tract-binding proteins by SUMO1.
AB  - Polypyrimidine tract-binding protein 1 (PTBP1) and its brainspecific homologue,
      PTBP2, are associated with pre-mRNAs and influence pre-mRNA processing, as well
      as mRNA metabolism and transport. They play important roles in neural
      differentiation and glioma development. In our study, we detected the expression
      of the two proteins in glioma cells and predicted that they may be sumoylated
      using SUMOplot analyses. We confirmed that PTBP1 and PTBP2 can be modified by
      SUMO1 with co-immunoprecipitation experiments using 293ET cells transiently co
      expressing SUMO1 and either PTBP1 or PTBP2. We also found that SUMO1 modification
      of PTBP2 was enhanced by Ubc9 (E2). The mutation of the sumoylation site (Lys137)
      of PTBP2 markedly inhibited its modification by SUMO1. Interestingly, in T98G
      glioma cells, the level of sumoylated PTBP2 was reduced compared to that of
      normal brain cells. Overall, this study shows that PTBP2 is posttranslationally
      modified by SUMO1.

PMID- 24286315
TI  - MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast
      cancers by targeting PTEN.
AB  - HER2-overexpressing breast cancers are characterized by frequent distant
      metastasis and often develop resistance after short-term effective treatment with
      the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic
      miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted
      metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was
      identified as a miR-221 target; overexpression of PTEN abrogated the
      aforementioned miR-221-induced malignant phenotypes of the cells. These findings
      indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2
      positive breast cancers by targeting PTEN, suggesting its role as a potential
      biomarker for progression and poor prognosis, and as a novel target for
      trastuzumab-combined treatment of breast cancers.

PMID- 24286316
TI  - Asn124 of Cel5A from Hypocrea jecorina not only provides the N-glycosylation site
      but is also essential in maintaining enzymatic activity.
AB  - To investigate the function of N-glycosylation of Cel5A (endoglucanase II) from
      Hypocrea jecorina, two N-glycosylation site deletion Cel5A mutants (rN124D and
      rN124H) were expressed in Saccharomyces cerevisiae. The weights of these
      recombinant mutants were 54 kDa, which were lower than that of rCel5A. This
      result was expected to be attributed to deglycosylation. The enzyme activity of
      rN124H was greatly reduced to 60.6% compared with rCel5A, whereas rN124D showed
      slightly lower activity (10%) than that of rCel5A. rN124D and rN124H showed
      different thermal stabilities compared with the glycosylated rCel5A, especially
      at lower pH value. Thermal stabilities were reduced and improved for rN124D and
      rN124H, respectively. Circular dichroism spectroscopy showed that the
      modification of secondary structure by mutation may be the reason for the change
      in enzymatic activity and thermal stability.

PMID- 24286317
TI  - Down-modulation of Bis reduces the invasive ability of glioma cells induced by
      TPA, through NF-kappaB mediated activation of MMP-9.
AB  - Bcl-2 interacting cell death suppressor (Bis) has been shown to have anti
      apoptotic and anti-stress functions. Recently, increased Bis expression was
      reported to correlate with glioma aggressiveness. Here, we investigated the
      effect of Bis knockdown on the acquisition of the invasive phenotype of A172
      glioma cells, induced by 12-O-Tetradecanoylphorbol-3-acetate (TPA), using a
      Transwell assay. Bis knockdown resulted in a significant decrease in the
      migration and invasion of A172 cells. Furthermore, Bis knockdown notably
      decreased TPA-induced matrix metalloproteinase-9 (MMP-9) activity and mRNA
      expression, as measured by zymography and quantitative real time PCR,
      respectively. A luciferase reporter assay indicated that Bis suppression
      significantly down-regulated NF-kappaB-driven transcription. Finally, we
      demonstrated that the rapid phosphorylation and subsequent degradation of IkappaB
      alpha induced by TPA was remarkably delayed by Bis knockdown. These results
      suggest that Bis regulates the invasive ability of glioma cells elicited by TPA,
      by modulating NF-kappaB activation, and subsequent induction of MMP-9 mRNA.

PMID- 24286318
TI  - Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL
      18 stimulation.
AB  - Inoculation of mice with the murine NFSA cell line caused the formation of large
      tumors with necrotic tumor cores. FACS analysis revealed accumulations of
      CD11b(+) cells in the tumors. Microarray analysis indicated that the NFSA cells
      expressed a high level of the pro-inflammatory factor interleukin-18 (il-18),
      which is known to play a critical role in macrophages. However, little is known
      about the physiological function of IL-18-stimulated macrophages. Here, we
      provide direct evidence that IL-18 enhances the phagocytosis of RAW264 cells and
      peritoneal macrophages, accompanied by the increased expression of tumor necrosis
      factor (tnf-alpha), interleukin-6 (il-6) and inducible nitric oxide synthase
      (Nos2). IL-18-stimulated RAW264 cells showed an enhanced cytotoxicity to
      endothelial F-2 cells via direct cell-to-cell interaction and the secretion of
      soluble mediators. Taken together, our results demonstrate that tumor-derived IL
      18 plays an important role in the phagocytosis of macrophages and that IL-18
      stimulated macrophages may damage tumor endothelial cells.

PMID- 24286319
TI  - The GABAB receptor associates with regulators of G-protein signaling 4 protein in
      the mouse prefrontal cortex and hypothalamus.
AB  - Regulators of G-protein signaling (RGS) proteins regulate certain G-protein
      coupled receptor (GPCR)-mediated signaling pathways. The GABA(B) receptor
      (GABA(B)R) is a GPCR that plays a role in the stress response. Previous studies
      indicate that acute immobilization stress (AIS) decreases RGS4 in the prefrontal
      cortex (PFC) and hypothalamus (HY) and suggest the possibility of a signal
      complex composed of RGS4 and GABA(B)R. Therefore, in the present study, we tested
      whether RGS4 associates with GABA(B)R in these brain regions. We found the co
      localization of RGS4 and GABA(B)R subtypes in the PFC and HY using double
      immunohistochemistry and confirmed a direct association between GABA(B2)R and
      RGS4 proteins using co-immunoprecipitation. Furthermore, we found that AIS
      decreased the amount of RGS4 bound to GABA(B2)R and the number of double-positive
      cells. These results indicate that GABA(B)R forms a signal complex with RGS4 and
      suggests that RGS4 is a regulator of GABA(B)R.

PMID- 24286320
TI  - Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1),
      leads to mitochondrial aberrations in mouse fibroblast NIH/3T3 cells.
AB  - Cancer cells undergo uncontrolled proliferation, and aberrant mitochondrial
      alterations. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a
      mitochondrial heat shock protein. TRAP1 mRNA is highly expressed in some cancer
      cell lines and tumor tissues. However, the effects of its overexpression on
      mitochondria are unclear. In this study, we assessed mitochondrial changes
      accompanying TRAP1 overexpression, in a mouse cell line, NIH/3T3. We found that
      overexpression of TRAP1 leads to a series of mitochondrial aberrations, including
      increase in basal ROS levels, and decrease in mitochondrial biogenesis, together
      with a decrease in peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) mRNA levels. We also observed increased extracellular signal
      regulated kinase (ERK) phosphorylation, and enhanced proliferation of TRAP1
      overexpressing cells. This study suggests that overexpression of TRAP1 might be a
      critical link between mitochondrial disturbances and carcinogenesis.

PMID- 24286321
TI  - Increased 26S proteasome non-ATPase regulatory subunit 1 in the aqueous humor of
      patients with age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      world. Evidence indicates that the suppression of the ubiquitin-proteasome system
      (UPS) contributes to the accumulation of toxic proteins and inflammation in
      retinal pigment epithelium (RPE), the functional abnormalities and/or the
      degeneration of which are believed to be the initiators and major pathologies of
      AMD. To identify new protein associations with the altered UPS in AMD, we used LC
      ESI-MS/MS to perform a proteomic analysis of the aqueous humor (AH) of AMD
      patients and matched control subjects. Six UPS-related proteins were present in
      the AH of the patients and control subjects. Four of the proteins, including 26S
      proteasome non-ATPase regulatory subunit 1 (Rpn2), were increased in patients,
      according to semi-quantitative proteomic profiling. An LC-MRM assay revealed a
      significant increase of Rpn2 in 15 AMD patients compared to the control subjects,
      suggesting that this protein could be a biomarker for AMD.

PMID- 24286323
TI  - Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis
      in human hepatoma HepG2 cells.
AB  - Plant sterols have shown potent anti-proliferative effects and apoptosis
      induction against breast and prostate cancers. However, the effect of sterols
      against hepatic cancer has not been investigated. In the present study, we
      assessed whether the stigmasterol isolated from Navicula incerta possesses
      apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the
      results, Stigmasterol has up-regulated the expression of pro-apoptotic gene
      expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2).
      Probably via mitochondrial apoptosis signaling pathway. With the induction of
      apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic
      cell numbers were observed through Hoechst staining, annexin V staining and cell
      cycle analysis. According to these results, we can suggest that the stigmasterol
      shows potent apoptosis inductive effects and has the potential to be tested as an
      anti-cancer therapeutic against liver cancer.

PMID- 24286322
TI  - Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via
      blockade of NF-kappaB and JNK activation in RAW 264.7 macrophages.
AB  - We isolated the phenolic glucoside salicortin from a Populus euramericana bark
      extract, and examined its ability to suppress inflammatory responses as well as
      the molecular mechanisms underlying these abilities, using lipopolysaccharide
      (LPS)-stimulated RAW264.7 cells. Salicortin inhibited iNOS expression and the
      subsequent production of NO in a dose-dependent manner in the LPS-stimulated RAW
      264.7 cells. Salicortin significantly suppressed LPS-induced signal cascades of
      NF-kappaB activation, such as IKK activation, IkappaBalpha phosphorylation and
      p65 phosphorylation in RAW 264.7 cells. In addition, salicortin inhibited the LPS
      induced activation of JNK, but not ERK or p38 MAPK. Furthermore, salicortin
      significantly inhibited production of pro-inflammatory cytokines, such as TNF
      alpha, IL-1beta and IL-6 in the LPS-stimulated RAW 264.7 cells. These findings
      suggest that salicortin may show its anti-inflammatory activity by suppressing
      the LPS-induced expression of pro-inflammatory mediators through inhibition of NF
      kappaB and JNK MAPK signaling cascades in macrophages.

PMID- 24286324
TI  - Nuclear localization signal domain of HDAC3 is necessary and sufficient for the
      expression regulation of MDR1.
AB  - Histone acetylation/deacetylation has been known to be associated with the
      transcriptional regulation of various genes. The role of histone deacetylase-3 in
      the expression regulation of MDR1 was investigated. The expression level of HDAC3
      showed an inverse relationship with the expression level of MDR1. Wild-type
      HDAC3, but not catalytic mutant HDAC3(S424A), negatively regulated the expression
      of MDR1. Wild-type HDAC3, but not catalytic mutant HDAC3(S424A), showed binding
      to the promoter sequences of HDAC3. HDAC3 regulated the expression level, and the
      binding of Ac-H3(K9/14) and Ac-H4(K16) around the MDR1 promoter sequences. The
      nuclear localization signal domain of HDAC3 was necessary, and sufficient for the
      binding of HDAC3 to the MDR1 promoter sequences and for conferring sensitivity to
      microtubule-targeting drugs.

PMID- 24286325
TI  - Gene-set based genome-wide association analysis for the speed of sound in two
      skeletal sites of Korean women.
AB  - The speed of sound (SOS) value is an indicator of bone mineral density (BMD).
      Previous genome-wide association (GWA) studies have identified a number of genes,
      whose variations may affect BMD levels. However, their biological implications
      have been elusive. We re-analyzed the GWA study dataset for the SOS values in
      skeletal sites of 4,659 Korean women, using a gene-set analysis software, GSA
      SNP. We identified 10 common representative GO terms, and 17 candidate genes
      between these two traits (PGS < 0.05). Implication of these GO terms and genes in
      the bone mechanism is well supported by the literature survey. Interestingly, the
      significance levels of some member genes were inversely related, in several gene
      sets that were shared between two skeletal sites. This implies that biological
      process, rather than SNP or gene, is the substantial unit of genetic association
      for SOS in bone. In conclusion, our findings may provide new insights into the
      biological mechanisms for BMD.

PMID- 24286326
TI  - Replication and packaging of Turnip yellow mosaic virus RNA containing Flock
      house virus RNA1 sequence.
AB  - Turnip yellow mosaic virus (TYMV) is a spherical plant virus that has a single
      6.3 kb positive strand RNA as a genome. In this study, RNA1 sequence of Flock
      house virus (FHV) was inserted into the TYMV genome to test whether TYMV can
      accommodate and express another viral entity. In the resulting construct,
      designated TY-FHV, the FHV RNA1 sequence was expressed as a TYMV subgenomic RNA.
      Northern analysis of the Nicotiana benthamiana leaves agroinfiltrated with the TY
      FHV showed that both genomic and subgenomic FHV RNAs were abundantly produced.
      This indicates that the FHV RNA1 sequence was correctly expressed and translated
      to produce a functional FHV replicase. Although these FHV RNAs were not
      encapsidated, the FHV RNA having a TYMV CP sequence at the 3'-end was efficiently
      encapsidated. When an eGFP gene was inserted into the B2 ORF of the FHV sequence,
      a fusion protein of B2-eGFP was produced as expected.

PMID- 24286328
TI  - Expression of a set of glial cell-specific markers in the Drosophila embryonic
      central nervous system.
AB  - The types of glia in the central nervous system (CNS) of the Drosophila embryo
      include longitudinal glia (LG), cell body glia (CBG), and peripheral glia (PG).
      Transcription factors, such as glial cell missing and reverse polarity, are well
      established general glial cell markers. Only a few glial cell-specific markers
      have been identified in the Drosophila embryonic CNS, thus far. In the present
      study, we employed the glial cell-specific markers for LG (vir-1/CG5453 and
      CG31235), CBG (fabp/CG6783 and CG11902), and PG (CG2310 and moody/CG4322), and
      comprehensively analyzed their expression patterns, during the embryonic CNS
      development. Our study validated the specificity of a set of glial markers, and
      further revealed their spatio-temporal expression patterns, which will aid in the
      understanding of the developmental lineage, and investigating their role in the
      development and homeostasis of the Drosophila CNS in vivo.

PMID- 24286327
TI  - Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in
      vitro and in vivo.
AB  - Endothelial cell protein C receptor (EPCR) plays important roles in blood
      coagulation and inflammation. EPCR activity is markedly changed by ectodomain
      cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface,
      which is mediated by tumor necrosis factor-alpha converting enzyme (TACE).
      Oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, is known
      to exhibit anti-angiogenic, antiinflammation, and anti-invasive activities.
      However, little is known about the effects of OroA on EPCR shedding. Data showed
      that OroA induced potent inhibition of phorbol-12-myristate 13-acetate (PMA),
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and on cecal ligation
      and puncture (CLP)-induced EPCR shedding through suppression of TACE expression
      and activity. In addition, treatment with OroA resulted in reduced PMA-stimulated
      phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N
      terminal kinase (JNK). These results demonstrate the potential of OroA as an anti
      sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.

PMID- 24286329
TI  - Berberine suppresses in vitro migration of human aortic smooth muscle cells
      through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-kappaB.
AB  - Berberine, a type of isoquinoline alkaloid isolated from Chinese medicinal herbs,
      has been reported to have various pharmacological activities. Studies have
      demonstrated that berberine has beneficial effects on vascular remodeling and
      alleviates restenosis after vascular injury. However, its mechanism of action on
      vascular smooth muscle cell migration is not fully understood. We therefore
      investigated the effect of berberine on human aortic smooth muscle cell (HASMC)
      migration. Boyden chamber assay was performed to show that berberine inhibited
      HASMC migration dosedependently. Real-time PCR and Western blotting analyses
      showed that levels of matrix metalloproteinase (MMP)-2, MMP-9, and urokinase-type
      plasminogen activator (u-PA) were reduced by berberine at both the mRNA and
      protein levels. Western blotting assay further confirmed that activities of c
      Fos, c-Jun, and NF-kappaB were significantly attenuated. These results suggest
      that berberine effectively inhibited HASMC migration, possibly by down-regulating
      MMP-2, MMP-9, and u-PA; and interrupting AP-1 and NF-kappaB mediated signaling
      pathways.

PMID- 24286330
TI  - Immunostimulating activity of maysin isolated from corn silk in murine RAW 264.7
      macrophages.
AB  - Corn silk (CS) has long been consumed as a traditional herb in Korea. Maysin is a
      major flavonoid of CS. The effects of maysin on macrophage activation were
      evaluated, using the murine macrophage RAW 264.7 cells. Maysin was isolated from
      CS by methanol extraction, and preparative C18 reverse phase column
      chromatography. Maysin was nontoxic up to 100 MUg/ml, and dose-dependently
      increased TNF-alpha secretion and iNOS production by 11.2- and 4.2-fold,
      respectively, compared to untreated control. The activation and subsequent
      nuclear translocation of NF-kappaB was substantially enhanced upon treatment with
      maysin (1-100 MUg/ml). Maysin also stimulated the phosphorylation of Akt and
      MAPKs (ERK, JNK). These results indicated that maysin activates macrophages to
      secrete TNF-alpha and induce iNOS expression, via the activation of the Akt, NF
      kappaB and MAPKs signaling pathways. These results suggest for the first time
      that maysin can be a new immunomodulator, enhancing the early innate immunity.

PMID- 24286331
TI  - Functional characterizations of residues Arg-158 and Tyr-170 of the mosquito
      larvicidal Bacillus thuringiensis Cry4Ba.
AB  - The insecticidal activity of Bacillus thuringiensis (Bt) Cry toxins involves
      toxin stabilization, oligomerization, passage across the peritrophic membrane
      (PM), binding to midgut receptors and pore-formation. The residues Arg-158 and
      Tyr-170 have been shown to be crucial for the toxicity of Bt Cry4Ba. We
      characterized the biological function of these residues. In mosquito larvae, the
      mutants R158A/E/Q (R158) could hardly penetrate the PM due to a significantly
      reduced ability to alter PM permeability; the mutant Y170A, however, could pass
      through the PM, but degraded in the space between the PM and the midgut
      epithelium. Further characterization by oligomerization demonstrated that Arg-158
      mutants failed to form correctly sized high-molecular weight oligomers. This is
      the first report that Arg-158 plays a role in the formation of Cry4Ba oligomers,
      which are essential for toxin passage across the PM. Tyr-170, meanwhile, is
      involved in toxin stabilization in the toxic mechanism of Cry4Ba in mosquito
      larvae.

PMID- 24286332
TI  - Antiplatelet and antithrombotic activities of purpurogallin in vitro and in vivo.
AB  - Enzymatic oxidation of pyrogallol was efficiently transformed to an oxidative
      product, purpurogallin (PPG). Here, the anticoagulant activities of PPG were
      examined by monitoring activated partial thromboplastin time (aPTT), prothrombin
      time (PT), and the activities of thrombin and activated factor X (FXa). And, the
      effects of PPG on expression of plasminogen activator inhibitor type 1 (PAI-1)
      and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis
      factor (TNF)-alpha activated human umbilical vein endothelial cells (HUVECs).
      Treatment with PPG resulted in prolonged aPTT and PT and inhibition of the
      activities of thrombin and FXa, as well as inhibited production of thrombin and
      FXa in HUVECs. In addition, PPG inhibited thrombin-catalyzed fibrin
      polymerization and platelet aggregation. PPG also elicited anticoagulant effects
      in mice. In addition, treatment with PPG resulted in significant reduction of the
      PAI-1 to t-PA ratio. Collectively, PPG possesses antithrombotic activities and
      offers a basis for development of a novel anticoagulant.

PMID- 24286333
TI  - An interview study for developing a user guide for powered seating function
      usage.
AB  - PURPOSE: Powered seating functions (PSFs) provide powered wheelchair users an
      independent means to adjust posture dynamically. To facilitate the best use of
      PSFs in daily living, we conducted this structured interview study to develop a
      preliminary user guide to provide "take-home" information to powered wheelchair
      users. METHOD: An internally developed questionnaire to assess clinical
      recommendations of PSF usage was administered in an interview format to clinical
      seating and mobility specialists. A qualitative analysis was applied to codify
      the recommendations, and the findings were transformed into a PSF user guide.
      RESULTS: Specific but varied seating positions and temporal indications were
      recommended for performing pressure relief positioning. For several activities,
      appropriate seating positions should be determined according to the immediate
      physical condition of the user and/or the environmental settings. CONCLUSION: The
      methods and positions of using PSFs should be determined with consideration for
      individual preferences, physical condition, environmental setting, and desired
      tasks after thorough clinical seating assessments. Precautions about positioning
      and driving safety, and the importance of discussing with clinicians are
      emphasized in the user guide. This PSF user guide will be updated after more
      scientific evidence accumulates and be structurally evaluated for its face and
      content validity in the future.

PMID- 24286334
TI  - Characterisation of ethylene pathway components in non-climacteric capsicum.
AB  - BACKGROUND: Climacteric fruit exhibit high ethylene and respiration levels during
      ripening but these levels are limited in non-climacteric fruit. Even though
      capsicum is in the same family as the well-characterised climacteric tomato
      (Solanaceae), it is non-climacteric and does not ripen normally in response to
      ethylene or if harvested when mature green. However, ripening progresses normally
      in capsicum fruit when they are harvested during or after what is called the
      'Breaker stage'. Whether ethylene, and components of the ethylene pathway such as
      1-aminocyclopropane 1-carboxylate (ACC) oxidase (ACO), ACC synthase (ACS) and the
      ethylene receptor (ETR), contribute to non-climacteric ripening in capsicum has
      not been studied in detail. To elucidate the behaviour of ethylene pathway
      components in capsicum during ripening, further analysis is therefore needed. The
      effects of ethylene or inhibitors of ethylene perception, such as 1
      methylcyclopropene, on capsicum fruit ripening and the ethylene pathway
      components may also shed some light on the role of ethylene in non-climacteric
      ripening. RESULTS: The expression of several isoforms of ACO, ACS and ETR were
      limited during capsicum ripening except one ACO isoform (CaACO4). ACS activity
      and ACC content were also low in capsicum despite the increase in ACO activity
      during the onset of ripening. Ethylene did not stimulate capsicum ripening but 1
      methylcyclopropene treatment delayed the ripening of Breaker-harvested fruit.
      Some of the ACO, ACS and ETR isoforms were also differentially expressed upon
      treatment with ethylene or 1-methylcyclopropene. CONCLUSIONS: ACS activity may be
      the rate limiting step in the ethylene pathway of capsicum which restricts ACC
      content. The differential expression of several ethylene pathway components
      during ripening and upon ethylene or 1-methylclopropene treatment suggests that
      the ethylene pathway may be regulated differently in non-climacteric capsicum
      compared to the climacteric tomato. Ethylene independent pathways may also exist
      in non-climacteric ripening as evidenced by the up-regulation of CaACO4 during
      ripening onset despite being negatively regulated by ethylene exposure. However,
      some level of ethylene perception may still be needed to induce ripening
      especially during the Breaker stage. A model of capsicum ripening is also
      presented to illustrate the probable role of ethylene in this non-climacteric
      fruit.

PMID- 24286335
TI  - Safety, tolerability, pharmacokinetics and pharmacodynamics of an anti-
      oncostatin M monoclonal antibody in rheumatoid arthritis: results from phase II
      randomized, placebo-controlled trials.
AB  - INTRODUCTION: Oncostatin M (OSM) has been implicated in the pathophysiology of
      rheumatoid arthritis (RA) through its effect on inflammation and joint damage.
      GSK315234 is a humanised anti-OSM Immunoglobulin G1 (IgG1) monoclonal antibody
      (mAb). This 3-part study examines the safety, tolerability and efficacy of
      GSK315234 in patients with active RA. METHOD: This was a 3-part (Parts A, B and
      C), multicenter study. Part A and Part B were randomised, double-blind, placebo
      controlled, Bayesian adaptive dose finding studies to investigate the safety,
      tolerability, efficacy, pharmacokinetics and pharmacodynamics of single (Part A)
      and 3 repeat (Part B) intravenous infusions of GSK315234 in patients with active
      RA on a background of methotrexate (MTX). Part C was a single dose, randomised,
      single-blind, placebo-controlled study to assess subcutaneously administered
      GSK315234 to patients with active RA on a background of MTX. RESULT: The primary
      endpoint of the study was mean change in DAS28 at Day 28 in Part A and Day 56 in
      Part B and C. All patients receiving at least one dose of GSK315234 were included
      in safety analysis. In Part A, there were statistically significant differences
      in DAS28 between 3 mg/kg and placebo at Day 56, 84 and 91. There was also a
      statistically significant difference in DAS28 between 0.3 mg/kg, 3 mg/kg and 10
      mg/kg, as compared to placebo, at Day 84. Although these changes were small and
      occurred late, they supported progression to Part B and C to determine the
      therapeutic potential of GSK315234. For Part B, no significant difference was
      observed between 6 mg/kg and placebo. For Part C, a statistically significant
      difference in DAS28 was observed at Day 40, Day 84 and Day 100 between the 500 mg
      subcutaneous group, as compared to placebo. No significant findings were observed
      at any of the time points for EULAR response criteria, ACR20, ACR50 or ACR70. An
      exploratory analysis of clinical, pharmacokinetic and pharmacodynamics data
      suggests the lack of efficacy may be due to moderate binding affinity and rapid
      off-rate of GSK315234 as compared to the higher affinity OSM receptor causing a
      protein carrier effect prolonging the half life of OSM due to accumulation of the
      OSM/antibody complex in the serum and synovial fluid. CONCLUSION: Our data
      highlighted the importance of binding affinity and off-rate effect of a mAb to
      fully neutralize the target and how this may influence its efficacy and
      potentially worsen disease activity. Using an anti-OSM mAb with high affinity
      should test this hypothesis and examine the potential of OSM as a therapeutic
      target in RA. TRIAL REGISTRATION: ClinicalTrials.gov no: NCT00674635.

PMID- 24286336
TI  - Structural and biochemical characterization of fructose-1,6/sedoheptulose-1,7
      bisphosphatase from the cyanobacterium Synechocystis strain 6803.
AB  - Cyanobacterial fructose-1,6/sedoheptulose-1,7-bisphosphatase (cy-FBP/SBPase)
      plays a vital role in gluconeogenesis and in the photosynthetic carbon reduction
      pathway, and is thus a potential enzymatic target for inhibition of harmful
      cyanobacterial blooms. Here, we describe the crystal structure of cy-FBP/SBPase
      in complex with AMP and fructose-1,6-bisphosphate (FBP). The allosteric inhibitor
      AMP and the substrate FBP exhibit an unusual binding mode when in complex with cy
      FBP/SBPase. Binding mode analysis suggested that AMP bound to the allosteric
      sites near the interface across the up/down subunit pairs C1C4 and C2C3 in the
      center of the tetramer, while FBP binds opposite to the interface between the
      horizontal subunit pairs C1C2 or C3C4. We identified a series of residues
      important for FBP and AMP binding, and suggest formation of a disulfide linkage
      between Cys75 and Cys99. Further analysis indicates that cy-FBP/SBPase may be
      regulated through ligand binding and alteration of the structure of the enzyme
      complex. The interactions between ligands and cy-FBP/SBPase are different from
      those of ligand-bound structures of other FBPase family members, and thus provide
      new insight into the molecular mechanisms of structure and catalysis of cy
      FBP/SBPase. Our studies provide insight into the evolution of this enzyme family,
      and may help in the design of inhibitors aimed at preventing toxic cyanobacterial
      blooms.

PMID- 24286337
TI  - Transcriptional landscapes of emerging autoimmunity: transient aberrations in the
      targeted tissue's extracellular milieu precede immune responses in Sjogren's
      syndrome.
AB  - INTRODUCTION: Our understanding of autoimmunity is skewed considerably towards
      the late stages of overt disease and chronic inflammation. Defining the targeted
      organ's role during emergence of autoimmune diseases is, however, critical in
      order to define their etiology, early and covert disease phases and delineate
      their molecular basis. METHODS: Using Sjogren's syndrome (SS) as an exemplary
      rheumatic autoimmune disease and temporal global gene-expression profiling, we
      systematically mapped the transcriptional landscapes and chronological
      interrelationships between biological themes involving the salivary glands'
      extracellular milieu. The time period studied spans from pre- to subclinical and
      ultimately to onset of overt disease in a well-defined model of spontaneous SS,
      the C57BL/6.NOD-Aec1Aec2 strain. In order to answer this aim of great generality,
      we developed a novel bioinformatics-based approach, which integrates
      comprehensive data analysis and visualization within interactive networks. The
      latter are computed by projecting the datasets as a whole on a priori-defined
      consensus-based knowledge. RESULTS: Applying these methodologies revealed
      extensive susceptibility loci-dependent aberrations in salivary gland homeostasis
      and integrity preceding onset of overt disease by a considerable amount of time.
      These alterations coincided with innate immune responses depending predominantly
      on genes located outside of the SS-predisposing loci Aec1 and Aec2. Following a
      period of transcriptional stability, networks mapping the onset of overt SS
      displayed, in addition to natural killer, T- and B-cell-specific gene patterns,
      significant reversals of focal adhesion, cell-cell junctions and neurotransmitter
      receptor-associated alterations that had prior characterized progression from pre
      to subclinical disease. CONCLUSIONS: This data-driven methodology advances
      unbiased assessment of global datasets an allowed comprehensive interpretation of
      complex alterations in biological states. Its application delineated a major
      involvement of the targeted organ during the emergence of experimental SS.

PMID- 24286338
TI  - Single-cell genomics reveal low recombination frequencies in freshwater bacteria
      of the SAR11 clade.
AB  - BACKGROUND: The SAR11 group of Alphaproteobacteria is highly abundant in the
      oceans. It contains a recently diverged freshwater clade, which offers the
      opportunity to compare adaptations to salt- and freshwaters in a monophyletic
      bacterial group. However, there are no cultivated members of the freshwater SAR11
      group and no genomes have been sequenced yet. RESULTS: We isolated ten single
      SAR11 cells from three freshwater lakes and sequenced and assembled their
      genomes. A phylogeny based on 57 proteins indicates that the cells are organized
      into distinct microclusters. We show that the freshwater genomes have evolved
      primarily by the accumulation of nucleotide substitutions and that they have
      among the lowest ratio of recombination to mutation estimated for bacteria. In
      contrast, members of the marine SAR11 clade have one of the highest ratios.
      Additional metagenome reads from six lakes confirm low recombination frequencies
      for the genome overall and reveal lake-specific variations in microcluster
      abundances. We identify hypervariable regions with gene contents broadly similar
      to those in the hypervariable regions of the marine isolates, containing genes
      putatively coding for cell surface molecules. CONCLUSIONS: We conclude that
      recombination rates differ dramatically in phylogenetic sister groups of the
      SAR11 clade adapted to freshwater and marine ecosystems. The results suggest that
      the transition from marine to freshwater systems has purged diversity and
      resulted in reduced opportunities for recombination with divergent members of the
      clade. The low recombination frequencies of the LD12 clade resemble the low
      genetic divergence of host-restricted pathogens that have recently shifted to a
      new host.

PMID- 24286339
TI  - Cross-sectional comparison of executive attention function in normally aging long
      term T'ai chi, meditation, and aerobic fitness practitioners versus sedentary
      adults.
AB  - This cross-sectional field study documented the effect of long-term t'ai chi,
      meditation, or aerobic exercise training versus a sedentary lifestyle on
      executive function. It was predicted that long-term training in t'ai chi and
      meditation plus exercise would produce greater benefits to executive function
      than aerobic exercise. T'ai chi and meditation plus exercise include mental and
      physical training. Fifty-four volunteers were tested: t'ai chi (n=10);
      meditation+exercise (n=16); aerobic exercisers (n=16); and sedentary controls
      (n=12). A one-factor (group), one-covariate (age) multivariate analysis of
      covariance was performed. Significant main effects of group and age were found
      (group, 67.9%, p<0.001; age, 76.3%, p=0.001). T'ai chi and meditation
      practitioners but not aerobic exercisers outperformed sedentary controls on
      percent switch costs (p=0.001 and p=0.006, respectively), suggesting that there
      may be differential effects of training type on executive function.

PMID- 24286340
TI  - Iyengar yoga therapy as an intervention for cramp management in individuals with
      amyotrophic lateral sclerosis: three case reports.
AB  - OBJECTIVES: Patients with amyotrophic lateral sclerosis (ALS), a
      neurodegenerative disease of motor neurons, experience cramps at all stages of
      the illness. There is, at present, no effective medication to control the cramps
      and no agreement on how to treat the symptom in ALS patients. SUBJECTS: Three
      individuals who were diagnosed with ALS and reported suffering cramps in various
      parts of the body, which limited their activities or affected their sleep were
      invited to try Iyengar yoga. INTERVENTION AND OUTCOME: Yoga therapy, composed of
      stretching, breathing, and relaxation exercises, was prescribed for each case,
      based on the subject's physical disability and the presence of other symptoms.
      Although two subjects experienced cramps during the first therapy session, all
      three subjects reported the complete cessation of cramping within 3 weeks to 8
      weeks of therapy. One of the subjects developed cramps in the hand after
      discontinuing yoga therapy for 7 months. However, the symptom stopped within 2
      weeks of resuming yoga therapy. CONCLUSION: The alleviation of cramps in these
      three subjects indicates the possibility of yogic intervention for the management
      of cramps in individuals with ALS, but further research is necessary to
      understand the effectiveness of yoga therapy and to determine the exercises that
      are more prone to lead to cramping in some ALS individuals.

PMID- 24286342
TI  - Patients with cystic fibrosis have a high carriage rate of non-toxigenic
      Clostridium difficile.
AB  - Thirty-year-old observations report frequent asymptomatic Clostridium difficile
      carriage among cystic fibrosis (CF) patients. In this case-control study, we
      found more carriers among CF patients than controls (47% versus 11%), but most
      strains carried by CF patients were non-toxigenic (77% versus 17%). Among CF
      patients, carriers were younger, with more severe pulmonary disease than non
      carriers. Strains belonged to multiple PCR-ribotypes, suggesting that these CF
      patients did not acquire strains from each other.

PMID- 24286341
TI  - A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with
      frontotemporal dementia.
AB  - AIMS: Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative
      disease and is the second most common form of young onset dementia after
      Alzheimer's disease (AD). An autosomal dominant pattern of inheritance is present
      in around 25-50% of FTLD cases indicating a strong genetic component. Major
      pathogenic mutations of FTLD have been demonstrated independently in the
      progranulin (GRN) gene and the C9orf72 hexanucleotide expansion repeat. In this
      study we present a family that have been identified as carrying both a GRN
      Cys31fs mutation and the C9orf72 hexanucleotide expansion repeat. METHODS: In the
      present study we describe the clinical and genetic details of family members and
      pathological features of two family members that have come to post-mortem.
      RESULTS: The mean age at disease onset was 57 years (48-61 years) and mean
      duration 4 years (2-7 years). The most common presenting syndrome was behavioural
      variant frontotemporal dementia. Brain imaging from available cases showed a
      symmetrical pattern of atrophy particularly affecting the frontal and temporal
      lobes. Pathologically two cases were classified as FTLD-TDP type A with TDP-43
      positive inclusions, with additional p62-positive 'star-like' inclusions found in
      the hippocampal formation and cerebellum. CONCLUSIONS: The type and distribution
      of the pathological lesions in these two cases were in keeping with FTLD cases
      carrying only the C9orf72 hexanucleotide repeat. However the driving force of the
      pathological process may be either pathogenic mutation or a combination of both
      converging on a singular mechanism.

PMID- 24286343
TI  - A faculty-facilitated near-peer teaching programme: an effective way of teaching
      undergraduate medical students.

PMID- 24286345
TI  - Can parallel use of different running shoes decrease running-related injury risk?
AB  - The aim of this study was to determine if runners who use concomitantly different
      pairs of running shoes are at a lower risk of running-related injury (RRI).
      Recreational runners (n = 264) participated in this 22-week prospective follow-up
      and reported all information about their running session characteristics, other
      sport participation and injuries on a dedicated Internet platform. A RRI was
      defined as a physical pain or complaint located at the lower limbs or lower back
      region, sustained during or as a result of running practice and impeding planned
      running activity for at least 1 day. One-third of the participants (n = 87)
      experienced at least one RRI during the observation period. The adjusted Cox
      regression analysis revealed that the parallel use of more than one pair of
      running shoes was a protective factor [hazard ratio (HR) = 0.614; 95% confidence
      interval (CI) = 0.389-0.969], while previous injury was a risk factor (HR =
      1.722; 95%CI = 1.114-2.661). Additionally, increased mean session distance (km;
      HR = 0.795; 95%CI = 0.725-0.872) and increased weekly volume of other sports
      (h/week; HR = 0.848; 95%CI = 0.732-0.982) were associated with lower RRI risk.
      Multiple shoe use and participation in other sports are strategies potentially
      leading to a variation of the load applied to the musculoskeletal system. They
      could be advised to recreational runners to prevent RRI.

PMID- 24286344
TI  - The progressive ankylosis gene product ANK regulates extracellular ATP levels in
      primary articular chondrocytes.
AB  - INTRODUCTION: Extracellular ATP (eATP) is released by articular chondrocytes
      under physiological and pathological conditions. High eATP levels cause
      pathologic calcification, damage cartilage, and mediate pain. We recently showed
      that stable over-expression of the progressive ankylosis gene product, ANK,
      increased chondrocyte eATP levels, but the mechanisms of this effect remained
      unexplored. The purpose of this work was to further investigate mechanisms of
      eATP efflux in primary articular chondrocytes and to better define the role of
      ANK in this process. METHODS: We measured eATP levels using a bioluminescence
      based assay in adult porcine articular chondrocyte media with or without a 10
      minute exposure to hypotonic stress. siRNAs for known ATP membrane transporters
      and pharmacologic inhibitors of ATP egress pathways were used to identify
      participants involved in chondrocyte eATP release. RESULTS: eATP levels increased
      after exposure to hypotonic media in a calcium-dependent manner in monolayer and
      3-dimensional agarose gel cultures (p < 0.001). A potent transient receptor
      potential vanilloid 4 (TRPV4) agonist mimicked the effects of hypotonic media.
      ANK siRNA suppressed basal (p < 0.01) and hypotonically-stressed (p < 0.001) ATP
      levels. This effect was not mediated by altered extracellular pyrophosphate
      (ePPi) levels, and was mimicked by the ANK inhibitor, probenecid (p < 0.001). The
      P2X7/4 receptor inhibitor Brilliant Blue G also suppressed eATP efflux induced by
      hypotonic media (p < 0.001), while ivermectin, a P2X4 receptor stimulant,
      increased eATP levels (p < 0.001). Pharmacologic inhibitors of hemichannels,
      maxianion channels and other volume-sensitive eATP efflux pathways did not
      suppress eATP levels. CONCLUSIONS: These findings implicate ANK and P2X7/4
      receptors in chondrocyte eATP efflux. Understanding the mechanisms of eATP efflux
      may result in novel therapies for calcium crystal arthritis and osteoarthritis.

PMID- 24286346
TI  - Measuring procedural fidelity in behavioural research.
AB  - Procedural fidelity (PF) refers to the implementation of a research plan, as
      intended. Measuring PF should be done not to satisfy minimum requirements for
      publication but to provide useful information to implementers, researchers, and
      consumers of research. Measurement of PF requires careful consideration and
      planning, and should include: naming important steps to be completed in each
      condition, defining each step, choosing a measurement system, determining which
      analysis is beneficial, training observers, conducting observations, analysing
      fidelity and identifying discrepancies, and reporting adequate data for
      consumers. Careful measurement and reporting of PF data will lead to advances in
      determining which interventions are effective, for whom, and under what
      conditions. 

PMID- 24286348
TI  - Registering grades of sudden deafness to predict the hearing outcome via an inner
      ear test battery.
AB  - OBJECTIVES: An inner ear test battery comprising audiometry and ocular vestibular
      evoked myogenic potential (oVEMP), cervical VEMP (cVEMP), and caloric tests was
      applied to patients with sudden deafness to map their lesions and predict hearing
      outcome. DESIGN: Retrospective study. STUDY SAMPLE: Seventy-five patients with
      unilateral sudden deafness underwent an inner-ear test battery. Registering the
      grades of sudden deafness was based on the number of abnormal test results in the
      inner ear test battery. RESULTS: After treatment for three consecutive months,
      mean hearing gain declined significantly from Grade I (one abnormal test) to
      Grade IV (four abnormal tests). Significant relations existed between hearing
      outcome and oVEMP test results (p < 0.05), caloric test results (p < 0.05), but
      not cVEMP test results and pre-treatment mean hearing level. Combined caloric and
      oVEMP test results demonstrated a stronger predictor with a c statistic of 0.722
      than either test alone, indicating that this regression model fits the whole set
      of observations well and is effective in predicting the hearing outcome.
      CONCLUSION: Abnormal caloric and oVEMP test results in sudden deafness patients
      may indicate poor prognosis for hearing improvement, whereas hearing recovery can
      be anticipated when both tests reveal normal responses.

PMID- 24286347
TI  - Berberine ameliorates cartilage degeneration in interleukin-1beta-stimulated rat
      chondrocytes and in a rat model of osteoarthritis via Akt signalling.
AB  - Berberine, a plant alkaloid used in Chinese medicine, has broad cell-protective
      functions in a variety of cell lines. Chondrocyte apoptosis contributes to the
      pathogenesis of cartilage degeneration in osteoarthritis (OA). However, little is
      known about the effect and underlying mechanism of berberine on OA chondrocytes.
      Here, we assessed the effects of berberine on cartilage degeneration in
      interleukin-1beta (IL-1beta)-stimulated rat chondrocytes and in a rat model of
      OA. The results of an MTT assay and western blotting analysis showed that
      berberine attenuated the inhibitory effect of IL-1beta on the cell viability and
      proliferating cell nuclear antigen expression in rat chondrocytes. Furthermore,
      berberine activated Akt, which triggered p70S6K/S6 pathway and up-regulated the
      levels of aggrecan and Col II expression in IL-1beta-stimulated rat chondrocytes.
      In addition, berberine increased the level of proteoglycans in cartilage matrix
      and the thickness of articular cartilage, with the elevated levels of Col II, p
      Akt and p-S6 expression in a rat OA model, as demonstrated by histopathological
      and immunohistochemistry techniques. The data thus strongly suggest that
      berberine may ameliorate cartilage degeneration from OA by promoting cell
      survival and matrix production of chondrocytes, which was partly attributed to
      the activation of Akt in IL-1beta-stimulated articular chondrocytes and in a rat
      OA model. The resultant chondroprotective effects indicate that berberine merits
      consideration as a therapeutic agent in OA. 

PMID- 24286349
TI  - Conversation tactics in persons with normal hearing and hearing-impairment.
AB  - OBJECTIVES: To investigate the tactics people use when aural communication fails
      owing to environmental circumstances or impaired hearing. DESIGN: Persons with
      different degrees of self-reported hearing impairment completed an online
      questionnaire constructed from items taken from the literature on communication
      strategies but reworded to be understood by people with normal hearing. Tactics
      were examined for frequency of use in two severities of impairment and between
      genders. All the data were then factor analysed and factor scores related to
      variables of relevance to communication. STUDY SAMPLE: A large convenience sample
      (n = 188) with a range of self-assessed hearing impairment from normal to
      profound. RESULTS: Descriptive data revealed some differences in frequency of use
      in relation to severity and gender. Factor analysis yielded six clearly
      interpretable factors, the largest relating to disengagement (avoidance). Self
      assessed impairment was chiefly associated with a speech reading tactic,
      negatively with environmental optimization strategies, and to a small extent with
      disengagement and conversation repair. CONCLUSIONS: Only the tactic of speech
      reading was closely associated with impaired hearing, with some evidence that
      females were more inclined to use it. Otherwise, all tactics were commonly
      employed, regardless of hearing status.

PMID- 24286350
TI  - SSF of steam-pretreated wheat straw with the addition of saccharified or
      fermented wheat meal in integrated bioethanol production.
AB  - BACKGROUND: Integration of second-generation (2G) bioethanol production with
      existing first-generation (1G) production may facilitate commercial production of
      ethanol from cellulosic material. Since 2G hydrolysates have a low sugar
      concentration and 1G streams often have to be diluted prior to fermentation,
      mixing of streams is beneficial. Improved ethanol concentrations in the 2G
      production process lowers energy demand in distillation, improves overall energy
      efficiency and thus lower production cost. There is also a potential to reach
      higher ethanol yields, which is required in economically feasible ethanol
      production. Integrated process scenarios with addition of saccharified wheat meal
      (SWM) or fermented wheat meal (FWM) were investigated in simultaneous
      saccharification and (co-)fermentation (SSF or SSCF) of steam-pretreated wheat
      straw, while the possibility of recovering the valuable protein-rich fibre
      residue from the wheat was also studied. RESULTS: The addition of SWM to SSF of
      steam-pretreated wheat straw, using commercially used dried baker's yeast, S.
      cerevisiae, resulted in ethanol concentrations of about 60 g/L, equivalent to
      ethanol yields of about 90% of the theoretical. The addition of FWM in batch mode
      SSF was toxic to baker's yeast, due to the ethanol content of FWM, resulting in a
      very low yield and high accumulation of glucose. The addition of FWM in fed-batch
      mode still caused a slight accumulation of glucose, but the ethanol concentration
      was fairly high, 51.2 g/L, corresponding to an ethanol yield of 90%, based on the
      amount of glucose added.In batch mode of SSCF using the xylose-fermenting,
      genetically modified S. cerevisiae strain KE6-12, no improvement was observed in
      ethanol yield or concentration, compared with baker's yeast, despite the
      increased xylose utilization, probably due to the considerable increase in
      glycerol production. A slight increase in xylose consumption was seen when
      glucose from SWM was fed at a low feed rate, after 48 hours, compared with batch
      SSCF. However, the ethanol yield and concentration remained in the same range as
      in batch mode. CONCLUSION: Ethanol concentrations of about 6% (w/v) were
      obtained, which will result in a significant reduction in the cost of downstream
      processing, compared with SSF of the lignocellulosic substrate alone. As an
      additional benefit, it is also possible to recover the protein-rich residue from
      the SWM in the process configurations presented, providing a valuable co-product.

PMID- 24286352
TI  - Abstracts of the Annual Congress of the British Society for Immunology. December
      2-5, 2013. Liverpool, United Kingdom.

PMID- 24286351
TI  - Histamine and gut mucosal immune regulation.
AB  - Histamine is a biogenic amine with extensive effects on many cell types, mediated
      by the activation of its four receptors (H1R-H4R). Distinct effects are dependent
      on receptor subtypes and their differential expression. Within the
      gastrointestinal tract, histamine is present at relatively high concentrations,
      particularly during inflammatory responses. In this review, we discuss the
      immunoregulatory influence of histamine on a number of gastrointestinal
      disorders, including food allergy, scombroid food poisoning, histamine
      intolerance, irritable bowel syndrome, and inflammatory bowel disease. It is
      clear that the effects of histamine on mucosal immune homeostasis are dependent
      on expression and activity of the four currently known histamine receptors;
      however, the relative protective or pathogenic effects of histamine on
      inflammatory processes within the gut are still poorly defined and require
      further investigation. 

PMID- 24286354
TI  - Epidermal stem cells ride the circadian wave.
AB  - An intriguing study shows that, in epidermal progenitor cells, circadian genes
      are expressed in successive waves that modulate responses to differentiation
      signals. 

PMID- 24286353
TI  - Multiple roles of the transcription factor AtMYBR1/AtMYB44 in ABA signaling,
      stress responses, and leaf senescence.
AB  - BACKGROUND: The transcription factor AtMYBR1 (MYB44) is a member of the MYB
      family of transcription factors and is expressed throughout the plant life cycle
      and especially in senescing and wounded leaves. It has previously been shown to
      be involved in responses to abiotic stress and is regulated by phosphorylation.
      RESULTS: When MYBR1 was over-expressed under the control of the constitutive 35S
      promoter in Arabidopsis thaliana (OxMYBR1), leaf senescence was delayed. In
      contrast loss-of-function mybr1 plants showed more rapid chlorophyll loss and
      senescence. The MYBR1 promoter strongly drove beta-GLUCURONIDASE reporter gene
      expression in tissues immediately after wounding and many wounding/pathogenesis
      genes were downregulated in OxMYBR1. OxMYBR1 plants were more susceptible to
      injury under water stress than wildtype, which was correlated with suppression of
      many ABA inducible stress genes in OxMYBR1. Conversely, mybr1 plants were more
      tolerant of water stress and exhibited reduced rates of water loss from leaves.
      MYBR1 physically interacted with ABA receptor PYR1-LIKE8 (PYL8) suggesting a
      direct involvement of MYBR1 in early ABA signaling. MYBR1 appears to exhibit
      partially redundant functions with AtMYBR2 (MYB77) and double mybr1 X mybr2
      mutants exhibited stronger senescence and stress related phenotypes than single
      mybr1 and mybr2 mutants. CONCLUSIONS: MYBR1 is a negative regulator of ABA,
      stress, wounding responses and blocks senescence. It appears to have a
      homeostatic function to maintain growth processes in the event of physical damage
      or stress.

PMID- 24286355
TI  - Hypoxia induces cell damage via oxidative stress in retinal epithelial cells.
AB  - Retinal diseases (RD), including diabetic retinopathy, are among the most
      important eye diseases in industrialized countries. RD is characterized by
      abnormal angiogenesis associated with an increase in cell proliferation and
      apoptosis. Hypoxia could be one of the triggers of the pathogenic mechanism of
      this disease. A key regulatory component of the cell's hypoxia response system is
      hypoxia-inducible factor 1 alpha (HIF-1alpha). It has been demonstrated that the
      induction of HIF-1alpha expression can be also achieved in vitro by exposure with
      cobalt chloride (CoCl2), leading to an intracellular hypoxia-like state. In this
      study we have investigated the effects of CoCl2 on human retinal epithelium cells
      (hRPE), which are an integral part of the blood-retinal barrier, with the aim to
      determine the possible role of oxidative stress in chemical hypoxia-induced
      damage in retinal epithelial cells. Our data showed that CoCl2 treatment is able
      to induce HIF-1alpha expression, that parallels with the formation of reactive
      oxygen species (ROS) and the increase of lipid 8-isoprostanes and 4
      hydroxynonenal (4-HNE) protein adducts levels. In addition we observed the
      activation of the redox-sensitive transcription factor nuclear factor-kappaB
      (NFkB) by CoCl2 which can explain the increased levels of vascular endothelial
      growth factor (VEGF). The increased number of dead cells seems to be related to
      an apoptotic process. Taken together these evidences suggest that oxidative
      stress induced by hypoxia might be involved in RD development through the
      stimulation of two key-events of RD such as neo-angiogenesis and apoptosis.

PMID- 24286356
TI  - Stearic acids at sn-1, 3 positions of TAG are more efficient at limiting fat
      deposition than palmitic and oleic acids in C57BL/6 mice.
AB  - In the present study, we investigated the effect of long-acyl chain SFA, namely
      palmitic acid (16:0) and stearic acid (18:0), at sn-1, 3 positions of TAG on
      obesity. Throughout the 15 weeks of the experimental period, C57BL/6 mice were
      fed diets fortified with cocoa butter, sal stearin (SAL), palm mid fraction (PMF)
      and high-oleic sunflower oil (HOS). The sn-1, 3 positions were varied by 16:0,
      18:0 and 18:1, whilst the sn-2 position was preserved with 18:1. The HOS-enriched
      diet was found to lead to the highest fat deposition. This was in accordance with
      our previous postulation. Upon normalisation of total fat deposited with food
      intake to obtain the fat:feed ratio, interestingly, mice fed the SAL-enriched
      diet exhibited significantly lower visceral fat/feed and total fat/feed compared
      with those fed the PMF-enriched diet, despite their similarity in SFA-unsaturated
      fatty acid-SFA profile. That long-chain SFA at sn-1, 3 positions concomitantly
      with an unsaturated FA at the sn-2 position exert an obesity-reducing effect was
      further validated. The present study is the first of its kind to demonstrate that
      SFA of different chain lengths at sn-1, 3 positions exert profound effects on fat
      accretion.

PMID- 24286357
TI  - [Risk factors of short term mortality in patients with acute ST-elevation
      myocardial infarction complicated with fatal arrhythmia].
AB  - OBJECTIVE: To explore the independent risk factors associated with short term
      mortality in patients with ST-segment elevation acute myocardial infarction
      (STEMI) complicated with fatal arrhythmia. METHODS: We analyzed data from Chinese
      STEMI patients with fatal arrhythmia enrolled in the CREATE trial. Predictors of
      30-day mortality after STEMI were identified by univariate and multivariate
      logistic regression analysis using baseline and therapy variables. RESULTS: The
      overall 30-day mortality of STEMI patients complicated with fatal arrhythmia
      among the 718 patients [(66.1 +/- 11.9) years and 62.4% male] was 52.9%. Logistic
      regression analysis showed that age (OR = 1.82, 95%CI:1.449-2.285), anterior
      infarction (OR = 4.419, 95%CI:2.645-7.384), heart rate > 60 bpm (OR = 3.32,
      95%CI:1.898- 5.808), killip class IV (OR = 3.686, 95%CI:1.684-8.06), admission
      hemoglobin A1c < 5.6% (OR = 2.564, 95%CI:1.199-5.484), no use of ACEI (OR =
      1.827, 95%CI:1.099-3.038) and no use of lipid-low drugs (OR = 2.034, 95%CI:1.196
      3.458) were independent risk factors for short term mortality after STEMI. The
      receiver operating characteristic curve for predicting the death of the baseline
      and clinical variable models was 0.830 (95%CI: 0.796-0.865) and 0.866 (95%CI:
      0.835-0.896), respectively. CONCLUSION: The 30-day mortality of patients with
      STEMI complicated with fatal arrhythmia is high. Age, anterior infarction, heart
      rate > 60 bpm, killip class IV, admission hemoglobin A1c level < 5.6%, no use of
      ACEI and no use of lipid-low drugs are independent risk factors for 30-day
      mortality in these patients.

PMID- 24286359
TI  - In vitro binding of [3H]PIB to human amyloid deposits of different types.
AB  - Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar
      proteins arranged in beta-pleated sheets. [(11)C]PIB has been used in PET studies
      to assess Abeta deposition in brain of patients with Alzheimer's disease (AD).
      The possibility to visualize other types of amyloid deposits with [(11)C]PIB
      would be of potential clinical importance in early diagnosis and for following
      therapeutic effects. In the present study, we evaluated in vitro binding of
      [(3)H]PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain
      (AL), amyloid protein A (AA) and Abeta amyloid. We found significantly higher
      binding of [(3)H]PIB in tissue from systemic amyloidoses than in control tissue,
      i.e. 4.7 times higher (p < 0.05). [(3)H]PIB showed the highest affinity to cortex
      of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and
      AL type of amyloidosis and large variations in affinity were observed even within
      tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which
      disrupts the beta-sheet structure, decreased the protein levels and,
      concomitantly, the binding of [(3)H]PIB in all four types of amyloidoses.

PMID- 24286358
TI  - Intra-articular CD1c-expressing myeloid dendritic cells from rheumatoid arthritis
      patients express a unique set of T cell-attracting chemokines and spontaneously
      induce Th1, Th17 and Th2 cell activity.
AB  - INTRODUCTION: Myeloid dendritic cells (mDCs) are potent T cell-activating antigen
      presenting cells that have been suggested to play a crucial role in the
      regulation of immune responses in many disease states, including rheumatoid
      arthritis (RA). Despite this, studies that have reported on the capacity of
      naturally occurring circulating mDCs to regulate T cell activation in RA are
      still lacking. This study aimed to evaluate the phenotypic and functional
      properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF)
      compared to those from peripheral blood (PB) of RA patients. METHODS: CD1c+ mDC
      numbers and expression of costimulatory molecules were assessed by fluorescence
      activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo
      secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was
      determined by multiplex immunoassay. The capacity of mDCs from SF to activate
      autologous CD4+ T cells was measured. RESULTS: CD1c+ mDC numbers were
      significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs
      from SF showed increased expression of antigen-presenting (human leukocyte
      antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40).
      Numerous cytokines were equally abundantly produced by mDCs from both PB and SF
      (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of
      interferon gamma-inducible protein-10 (IP-10), monokine induced by interferon
      gamma (MIG) and, thymus and activation-regulated chemokine (TARC), but lower
      macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF
      displayed a strongly increased capacity to induce proliferation of CD4+ T cells
      associated with a strongly augmented IFNgamma, IL-17, and IL-4 production.
      CONCLUSIONS: This study suggests that increased numbers of CD1c+ mDCs in SF are
      involved in the inflammatory cascade intra-articularly by the secretion of
      specific T cell-attracting chemokines and the activation of self-reactive T
      cells.

PMID- 24286360
TI  - Melatonin for sedative withdrawal in older patients with primary insomnia: a
      randomized double-blind placebo-controlled trial.
AB  - AIM: We compared the efficacy of melatonin and placebo as adjuvants in the
      withdrawal of patients from long term temazepam, zopiclone or zolpidem (here
      'BZD') use. METHODS: A double-blind, placebo-controlled, randomized trial was
      conducted in a primary health care outpatient clinic. Ninety-two men or women
      (>=55 years) with primary insomnia and chronic BZD use received controlled
      release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month
      withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for
      up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by
      BZD plasma determinations, while reduction in BZD use and abstinence continuing
      for 6 months were noted. RESULTS: There were two drop-outs on CRM and one on
      placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM
      and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat
      analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use
      was similar or even more rare in the CRM than in the placebo group (P = 0.052 per
      protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo
      group remained non-users of BZD (NS between groups). BZD doses were higher in the
      CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025).
      Withdrawal symptoms did not differ between the groups. CONCLUSIONS: Gradual dose
      reduction of BZDs combined with CRM or placebo, and psychosocial support produced
      high short term and moderate long term BZD abstinence. CRM showed no withdrawal
      benefit compared with placebo.

PMID- 24286361
TI  - Two faces of inflammation: an immunopharmacological view.
AB  - Inflammation is a protective response intended to eliminate pathogens and other
      offending agents which have potential to cause cell injury, as well as malignant
      and necrotic cells. However, if the inflammatory response is dysregulated or
      inappropriately focused, it has considerable potential to cause harm and can lead
      to development of inflammatory diseases such as allergic and autoimmune diseases.
      Despite the recent success in cytokine-targeted therapies, for example by the use
      of specific biological drugs, there are still considerable unmet needs in the
      treatment of inflammatory diseases. Further, recent discoveries in many diseases
      in addition to the classical inflammatory diseases have revealed inflammation to
      be a major factor participating in the underlying pathophysiological processes,
      either through activation of inflammatory cells or through triggering of
      inflammatory signalling mechanisms in the tissue cells. Examples of such diseases
      and conditions are many cardiovascular, metabolic and degenerative diseases, as
      well as cancer, obesity and pain. This brings the immunopharmacological approach
      into a new perspective in the drug development in very wide therapeutic areas.
      Immunopharmacology investigates mechanisms of inflammation and potential
      molecules and targets to treat inflammatory diseases. The current issue of Basic
      and Clinical Pharmacology and Toxicology focuses on some of the novel
      inflammatory mechanisms with potential in anti-inflammatory drug development,
      including kinase pathways, TRP ion channels, eicosanoid system, obesity-related
      adipokines, autoantibodies against citrullinated proteins, eosinophils, platelets
      and pathways connecting nervous and immune systems. The MiniReviews are based on
      lectures given at the symposium "Novel Drugs and Drug Targets to Treat
      Inflammation" in Yllas, Finland, in March 2013. 

PMID- 24286362
TI  - Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis
      with polyangiitis (Churg-Strauss syndrome).
AB  - INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is part of
      antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA
      small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of
      EGPA patients are ANCA-positive, suggesting a role for B cells in the
      pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be
      effective in ANCA-positive EGPA, but very few patients have been published to
      date. The role of RTX in the treatment of ANCA-negative EGPA is unclear. METHODS:
      We report a single-center cohort of patients with eosinophilic granulomatosis
      with polyangiitis. Of these patients, nine (six ANCA-positive, three ANCA
      negative) had been treated with RTX for relapsing or refractory disease on
      standard immunosuppressive treatment. In a retrospective analysis, data on
      treatment response, frequency of relapses, adverse events, and peripheral B-cell
      reconstitution were evaluated. Furthermore, serum immunoglobulin concentrations,
      ANCA status, and peripheral B cell subpopulations were assessed after RTX
      treatment. RESULTS: All patients had high disease activity before RTX treatment.
      At presentation 3 months after RTX therapy, all ANCA-positive and ANCA-negative
      patients had responded to RTX, with one patient being in complete remission, and
      eight patients being in partial remission. After a mean follow-up of 9 months, C
      reactive protein concentrations had normalized, eosinophils had significantly
      decreased, and prednisone had been tapered in all patients. In all patients, RTX
      therapy was combined with a standard immunosuppressive therapy. Within the 9
      month observation period, no relapse was recorded. Three patients were
      preemptively retreated with RTX, and during the median follow-up time of 3 years,
      no relapse occurred in these patients. During the follow-up of 13 patient-years,
      five minor but no major infections were recorded. CONCLUSIONS: In our analysis on
      nine patients with EGPA resistant to standard therapy, rituximab proved to be an
      efficient and safe treatment for ANCA-positive and ANCA-negative patients.
      Preemptive retreatment with RTX, combined with standard maintenance
      immunosuppressants, resulted in a sustained treatment response. Prospective,
      randomized trials evaluating the use of RTX in EGPA are warranted.

PMID- 24286363
TI  - Lack of isocitrate lyase in Chlamydomonas leads to changes in carbon metabolism
      and in the response to oxidative stress under mixotrophic growth.
AB  - Isocitrate lyase is a key enzyme of the glyoxylate cycle. This cycle plays an
      essential role in cell growth on acetate, and is important for gluconeogenesis as
      it bypasses the two oxidative steps of the tricarboxylic acid (TCA) cycle in
      which CO2 is evolved. In this paper, a null icl mutant of the green microalga
      Chlamydomonas reinhardtii is described. Our data show that isocitrate lyase is
      required for growth in darkness on acetate (heterotrophic conditions), as well as
      for efficient growth in the light when acetate is supplied (mixotrophic
      conditions). Under these latter conditions, reduced acetate assimilation and
      concomitant reduced respiration occur, and biomass composition analysis reveals
      an increase in total fatty acid content, including neutral lipids and free fatty
      acids. Quantitative proteomic analysis by 14N/15N labelling was performed, and
      more than 1600 proteins were identified. These analyses reveal a strong decrease
      in the amounts of enzymes of the glyoxylate cycle and gluconeogenesis in parallel
      with a shift of the TCA cycle towards amino acid synthesis, accompanied by an
      increase in free amino acids. The decrease of the glyoxylate cycle and
      gluconeogenesis, as well as the decrease in enzymes involved in beta-oxidation of
      fatty acids in the icl mutant are probably major factors that contribute to
      remodelling of lipids in the icl mutant. These modifications are probably
      responsible for the elevation of the response to oxidative stress, with
      significantly augmented levels and activities of superoxide dismutase and
      ascorbate peroxidase, and increased resistance to paraquat.

PMID- 24286364
TI  - Nocturnal polyuria and decreased serum testosterone: is there an association in
      men with lower urinary tract symptoms?
AB  - OBJECTIVES: To investigate the putative association between nocturia and
      decreased serum testosterone in men with lower urinary tract symptoms. METHODS:
      Frequency volume charts and serum testosterone levels of patients visiting the
      outpatient clinic for lower urinary tract symptoms were collected and analyzed.
      Age, prostate volume, body mass index and the presence of comorbidities were
      accounted for. Frequency volume charts were analyzed for pathophysiological
      components of nocturnal polyuria, global polyuria, decreased nocturnal bladder
      capacity and increased frequency to identify associated risks. Frequency volume
      charts were also used to chart 8-h changes of volume, frequency and capacity to
      identify time diurnal interactions with risk factors based on serum testosterone
      levels. RESULTS: A total of 2180 patients were enrolled in the study.
      Multivariate analysis showed testosterone decreased 0.142 ng/mL for every
      increase in nocturia, independent of other factors. Logistic regression analysis
      showed a significant difference between pathophysiological components. Decreased
      testosterone was shown to carry a significant independent risk for overall
      nocturia (odds ratio 1.60, 95% confidence interval 1.013-2.527, P = 0.044), and
      particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001
      3.737, P = 0.027). Repeated measurement models showed patients with serum
      testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine
      volume at night. CONCLUSIONS: Nocturia, especially nocturnal polyuria, is
      associated with decreased serum testosterone. Patients with low serum
      testosterone show increased nocturnal urine output.

PMID- 24286365
TI  - Does everything happen when you are young? Introducing the youth bias.
AB  - The reminiscence bump refers to the disproportionate number of individuals'
      autobiographical memories that date from young adulthood. A similar bump is found
      in cultural life scripts: When people are asked to nominate and date major
      transitional events in a typical life course in their culture, a disproportionate
      number of the events cited are likewise expected to occur in young adulthood.
      Across two online studies, we tested whether these effects reflect a broader
      tendency to ascribe most important events to young adulthood. Specifically, we
      probed, in adult USA samples, for when individuals expect the most important
      public event of a typical person's life to take place. Although the occurrence of
      such public events should be randomly distributed across the lifespan, we found a
      bump in young adulthood. We found this bump in both subjective (Study 1; probing
      cultural expectations for the expected timing of the public event that a typical
      person considers to be the most important of their lifetime) and objective (Study
      2; probing cultural expectations for the expected timing of the objectively most
      important public event of a typical person's lifetime) conditions. We term this
      set of cultural expectations the youth bias and discuss its implications for
      human cognition. 

PMID- 24286366
TI  - Sialoadhesin deficiency does not influence the severity of lupus nephritis in New
      Zealand black x New Zealand white F1 mice.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic inflammatory
      condition with multisystem involvement. One of the key features of the disease is
      the upregulation of type I interferons, resulting in the so-called "interferon
      signature". Recent flow cytometric and transcriptomic studies identified
      Sialoadhesin (Sn, CD169) as an important interferon-induced blood monocyte
      biomarker in diseased patients. To investigate a potential causative role of Sn
      in SLE, we generated NZBWF1 (New Zealand Black x New Zealand White F1) mice
      lacking Sn and compared onset and progression of disease with NZBWF1 expressing
      normal levels of Sn. METHODS: Sn expression in renal tissues of pre-diseased and
      diseased NZBWF1 mice was evaluated by Quantitative real time PCR (QPCR) and
      immunohistochemistry. Sn-/- NZBWF1 mice were generated by speed congenics.
      Disease severity of Sn+/+ and Sn-/- NZBWF1 mice was assessed by serum
      immunoassays, flow cytometry, light microscopy and immunohistochemistry. RESULTS:
      Renal tissues from proteinuric NZBWF1 mice exhibited a significant upregulation
      of Sn mRNA and protein expression following disease onset. Further
      immunohistochemical analysis showed that Sn+ macrophages assumed a distinct
      periglomerular distribution and, unlike CD68+ macrophages, were not present
      within the glomeruli. Analysis of disease severity in Sn-/- and Sn+/+ NZBWF1 mice
      revealed no significant differences in the disease progression between the two
      groups although Sn-deficient mice showed a more rapid onset of proteinuria.
      CONCLUSIONS: These data confirm a positive correlation of Sn with disease
      activity. However, Sn deficiency does not have a significant effect on the
      severity and progression of lupus nephritis in the NZBWF1 mouse model.

PMID- 24286367
TI  - Long-term follow-up of a facilitated peer mentoring program.
AB  - BACKGROUND: Mentoring plays an important role in career success of academic
      medical faculty. New mentoring models such as peer mentoring have emerged. AIM:
      To evaluate the long-term impact of a facilitated peer mentoring program on
      academic achievements. METHOD: Women faculty at the instructor or assistant
      professor rank were recruited to voluntarily participate in a facilitated peer
      mentoring program. Recruitment occurred over 3.8 years between 2005 and 2009. A
      26-item questionnaire to assess academic skill, career satisfaction, and self
      efficacy was administered before program participation and again with seven
      additional questions in 2011. Curriculum vitae were reviewed retrospectively to
      tally peer-reviewed publications, other academic activities, and promotions.
      RESULTS: Participants had long-term improvement in their perceived mastery of
      academic skills. Peer-reviewed publications, book chapters, abstracts, posters,
      and other academic activities increased when activities before the program were
      compared to those in the five years after program enrollment. At follow-up,
      participants reported positive perceptions of the program and 44% continued to
      work with their original peer mentor groups. CONCLUSIONS: Involvement in the
      facilitated peer mentoring program was associated with increased skills and
      academic activities for most participants. Future studies are needed to assess
      its applicability and success among various demographic groups in academic
      medicine.

PMID- 24286368
TI  - Cordycepin activates AMP-activated protein kinase (AMPK) via interaction with the
      gamma1 subunit.
AB  - Cordycepin is a bioactive component of the fungus Cordyceps militaris.
      Previously, we showed that cordycepin can alleviate hyperlipidemia through
      enhancing the phosphorylation of AMP-activated protein kinase (AMPK), but the
      mechanism of this stimulation is unknown. Here, we investigated the potential
      mechanisms of cordycepin-induced AMPK activation in HepG2 cells. Treatment with
      cordycepin largely reduced oleic acid (OA)-elicited intracellular lipid
      accumulation and increased AMPK activity in a dose-dependent manner. Cordycepin
      induced AMPK activation was not accompanied by changes in either the
      intracellular levels of AMP or the AMP/ATP ratio, nor was it influenced by
      calmodulin-dependent protein kinase kinase (CaMKK) inhibition; however, this
      activation was significantly suppressed by liver kinase B1 (LKB1) knockdown.
      Molecular docking, fluorescent and circular dichroism measurements showed that
      cordycepin interacted with the gamma1 subunit of AMPK. Knockdown of AMPKgamma1 by
      siRNA substantially abolished the effects of cordycepin on AMPK activation and
      lipid regulation. The modulating effects of cordycepin on the mRNA levels of key
      lipid regulatory genes were also largely reversed when AMPKgamma1 expression was
      inhibited. Together, these data suggest that cordycepin may inhibit intracellular
      lipid accumulation through activation of AMPK via interaction with the gamma1
      subunit. 

PMID- 24286370
TI  - Protective effect of taraxasterol against LPS-induced endotoxic shock by
      modulating inflammatory responses in mice.
AB  - Taraxasterol, a pentacyclic-triterpene, was isolated from the Chinese medicinal
      herb Taraxacum officinale. In the present study, we investigated the protective
      effect of taraxasterol on murine model of endotoxic shock and the mechanism of
      its action. Mice were treated with 2.5, 5 and 10 mg/kg of taraxasterol prior to a
      lethal dose of lipopolysaccharide (LPS) challenge. Survival of mice was monitored
      twice a day for 7 days. To further understand the mechanism, the serum levels of
      inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), interferon-gamma
      (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and mediator
      nitric oxide (NO), prostaglandin E2 (PGE2) as well as histology of lungs were
      examined. The results showed that taraxasterol significantly improved mouse
      survival and attenuated tissue injury of the lungs in LPS-induced endotoxemic
      mice. Further studies revealed that taraxasterol significantly reduced TNF-alpha,
      IFN-gamma, IL-1beta, IL-6, NO and PGE2 levels in sera from mice with endotoxic
      shock. These results indicate that taraxasterol has a protective effect on murine
      endotoxic shock induced by LPS through modulating inflammatory cytokine and
      mediator secretion. This finding might provide a new strategy for the treatment
      of endotoxic shock and associated inflammation.

PMID- 24286371
TI  - A comparison of the effects of topical treatment of calcipotriol, camptothecin,
      clobetasol and tazarotene on an imiquimod-induced psoriasis-like mouse model.
AB  - The interleukin-23/interleukin 17A (IL-23/IL-17A) cytokine axis plays a critical
      role in the pathogenesis of psoriasis. In this study, we report the effects of
      topical calcipotriol, camptothecin, clobetasol and tazarotene on the treatment of
      imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which is
      dependent on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and
      inflammation in the BALB/c mouse ear were significantly inhibited following
      clobetasol treatment but not calcipotriol, camptothecin or tazarotene treatments.
      Real-time polymerase chain reaction showed that the mRNA levels of IL-17A, IL
      17F, IL-22, IL-1beta, IL-6 and TNF-alpha in ear skin were significantly decreased
      by clobetasol. In addition, we observed that calcipotriol, camptothecin and
      tazarotene failed to show any inhibitory effects on the IL-23/IL-17A/IL-22 axis.
      We also found that clobetasol treatment inhibited the proliferation of gammadelta
      T cells and C-C chemokine receptor type 6 (CCR6) expression induced by IMQ.
      Calcipotriol, camptothecin and tazarotene not only failed to inhibit this
      proliferation but also enhanced retinoic acid-related orphan receptor gamma
      (RORgamma) expression in IMQ-induced psoriasis-like inflammation. In conclusion,
      we suggest that clobetasol induces the relief of IMQ-induced psoriasis-like
      inflammation in a mouse model but that calcipotriol, camptothecin and tazarotene
      cannot. Therefore, we suggest that more in-depth studies on pharmacological
      effects of tazarotene, camptothecin and calcipotriol should be carried out.

PMID- 24286372
TI  - Towards an energetic landscape: broad-scale accelerometry in woodland caribou.
AB  - Energetic balance is a central driver of individual survival and population
      change, yet estimating energetic costs in free- and wide-ranging animals presents
      a significant challenge. Animal-borne activity monitors (using accelerometer
      technology) present a promising method of meeting this challenge and open new
      avenues for exploring energetics in natural settings. To determine the behaviours
      and estimated energetic costs associated with a given activity level, three
      captive reindeer (Rangifer tarandus tarandus) at the Toronto Zoo were fitted with
      collars and observed for 53 h. Activity patterns were then measured over 13
      months for 131 free-ranging woodland caribou (R. t. caribou) spanning 450,000
      km(2) in northern Ontario. The captive study revealed a positive but decelerating
      relationship between activity level and energetic costs inferred from previous
      behavioural studies. Field-based measures of activity were modelled against
      individual displacement, vegetation abundance (Normalized Difference Vegetation
      Index), snow depth and temperature, and the best fit model included all
      parameters and explained over half of the variation in the data. Individual
      displacement was positively related to activity levels, suggesting that broad
      differences in energetic demands are influenced by variation in movement rates.
      After accounting for displacement, activity was highest at intermediate levels of
      vegetation abundance, presumably due to foraging behaviour. Snow depth, probably
      associated with digging for winter forage, moderately increased activity.
      Activity levels increased significantly at the coldest winter temperatures,
      suggesting the use of behavioural thermoregulation by caribou. These
      interpretations of proximate causal factors should be regarded as hypotheses
      subject to validation under normal field conditions. These results illustrate the
      landscape characteristics that increase energetic demands for caribou and confirm
      the great potential for the use of accelerometry in studies of animal energetics.

PMID- 24286373
TI  - Stability, genotypic and phenotypic diversity of Shewanella baltica in the redox
      transition zone of the Baltic Sea.
AB  - Studying how bacterial strains diverge over space and time and how divergence
      leads to ecotype formation is important for understanding structure and dynamics
      of environmental communities. Here we assess the ecological speciation and
      temporal dynamics of a collection of Shewanella baltica strains from the redox
      transition zone of the central Baltic Sea, sampled at three time points over a
      course of 12 years, with a subcollection containing 46 strains subjected to
      detailed genetic and physiological characterization. Nine clades were
      consistently recovered by three different genotyping approaches: gyrB gene
      sequencing, multilocus sequence typing (MLST) and whole genome clustering of data
      from comparative genomic hybridization, and indicated specialization according to
      nutrient availability, particle association and temporal distribution. Genomic
      analysis suggested higher intra- than inter-clade recombination that might result
      from niche partitioning. Substantial heterogeneity in carbon utilization and
      respiratory capabilities suggested rapid diversification within the same 'named'
      species and physical habitat and showed consistency with genetic relatedness. At
      least two major ecotypes, represented by MLST clades A and E, were proposed based
      on genetic, ecological and physiological distinctiveness. This study suggests
      that genetic analysis in conjunction with phenotypic evaluation can provide
      better understanding of the ecological framework and evolutionary trajectories of
      microbial species. 

PMID- 24286374
TI  - Optimization of NaOH-catalyzed steam pretreatment of empty fruit bunch.
AB  - BACKGROUND: Empty fruit bunch (EFB) has many advantages, including its abundance,
      the fact that it does not require collection, and its year-round availability as
      a feedstock for bioethanol production. But before the significant costs incurred
      in ethanol production from lignocellulosic biomass can be reduced, an efficient
      sugar fractionation technology has to be developed. To that end, in the present
      study, an NaOH-catalyzed steam pretreatment process was applied in order to
      produce ethanol from EFB more efficiently. RESULTS: The EFB pretreatment
      conditions were optimized by application of certain pretreatment variables such
      as, the NaOH concentrations in the soaking step and, in the steam step, the
      temperature and time. The optimal conditions were determined by response surface
      methodology (RSM) to be 3% NaOH for soaking and 160 degrees C, 11 min 20 sec for
      steam pretreatment. Under these conditions, the overall glucan recovery and
      enzymatic digestibility were both high: the glucan and xylan yields were 93% and
      78%, respectively, and the enzymatic digestibility was 88.8% for 72 h using 40
      FPU/g glucan. After simultaneous saccharification and fermentation (SSF), the
      maximum ethanol yield and concentration were 0.88 and 29.4 g/l respectively.
      CONCLUSIONS: Delignification (>85%) of EFB was an important factor in enzymatic
      hydrolysis using CTec2. NaOH-catalyzed steam pretreatment, which can remove
      lignin efficiently and requires only a short reaction time, was proven to be an
      effective pretreatment technology for EFB. The ethanol yield obtained by SSF, the
      key parameter determining the economics of ethanol, was 18% (w/w), equivalent to
      88% of the theoretical maximum yield, which is a better result than have been
      reported in the relevant previous studies.

PMID- 24286375
TI  - Characterizing 5-methylcytosine in the mammalian epitranscriptome.
AB  - The post-transcriptional modification 5-methylcytosine (m5C) occurs in a wide
      range of coding and non-coding RNAs. We describe transcriptome-wide approaches to
      capture the global m5C RNA methylome. We also discuss the potential functions of
      m5C in RNA and compare them to 6-methyladenosine modifications.

PMID- 24286377
TI  - New developments on NUCB2/nesfatin-1.

PMID- 24286376
TI  - Adverse outcomes in maternity care for women with a low risk profile in The
      Netherlands: a case series analysis.
AB  - BACKGROUND: This study aimed to perform a structural analysis of determinants of
      risk of critical incidents in care for women with a low risk profile at the start
      of pregnancy with a view on improving patient safety. METHODS: We included 71
      critical incidents in primary midwifery care and subsequent hospital care in case
      of referral after 36 weeks of pregnancy that were related to substandard care and
      for that reason were reported to the Health Care Inspectorate in The Netherlands
      in 36 months (n = 357). We performed a case-by-case analysis, using a previously
      validated instrument which covered five broad domains: healthcare organization,
      communication between healthcare providers, patient risk factors, clinical
      management, and clinical outcomes. RESULTS: Determinants that were associated
      with risk concerned healthcare organization (n = 20 incidents), communication
      about treatment procedures (n = 39), referral processes (n = 19), risk assessment
      by telephone triage (n = 10), and clinical management in an out of hours setting
      (n = 19). The 71 critical incidents included three cases of maternal death, eight
      cases of severe maternal morbidity, 42 perinatal deaths and 12 critical incidents
      with severe morbidity for the child. Suboptimal prenatal risk assessment, a delay
      in availability of health care providers in urgent situations, miscommunication
      about treatment between care providers, and miscommunication with patients in
      situations with a language barrier were associated with safety risks.
      CONCLUSIONS: Systematic analysis of critical incidents improves insight in
      determinants of safety risk. The wide variety of determinants of risk of critical
      incidents implies that there is no single intervention to improve patient safety
      in the care for pregnant women with initially a low risk profile.

PMID- 24286369
TI  - Critical research gaps and translational priorities for the successful prevention
      and treatment of breast cancer.
AB  - INTRODUCTION: Breast cancer remains a significant scientific, clinical and
      societal challenge. This gap analysis has reviewed and critically assessed
      enduring issues and new challenges emerging from recent research, and proposes
      strategies for translating solutions into practice. METHODS: More than 100
      internationally recognised specialist breast cancer scientists, clinicians and
      healthcare professionals collaborated to address nine thematic areas: genetics,
      epigenetics and epidemiology; molecular pathology and cell biology; hormonal
      influences and endocrine therapy; imaging, detection and screening; current/novel
      therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating
      tumour cells, cancer 'stem' cells; risk and prevention; living with and managing
      breast cancer and its treatment. The groups developed summary papers through an
      iterative process which, following further appraisal from experts and patients,
      were melded into this summary account. RESULTS: The 10 major gaps identified
      were: (1) understanding the functions and contextual interactions of genetic and
      epigenetic changes in normal breast development and during malignant
      transformation; (2) how to implement sustainable lifestyle changes (diet,
      exercise and weight) and chemopreventive strategies; (3) the need for tailored
      screening approaches including clinically actionable tests; (4) enhancing
      knowledge of molecular drivers behind breast cancer subtypes, progression and
      metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity,
      dormancy, de novo or acquired resistance and how to target key nodes in these
      dynamic processes; (6) developing validated markers for chemosensitivity and
      radiosensitivity; (7) understanding the optimal duration, sequencing and rational
      combinations of treatment for improved personalised therapy; (8) validating
      multimodality imaging biomarkers for minimally invasive diagnosis and monitoring
      of responses in primary and metastatic disease; (9) developing interventions and
      support to improve the survivorship experience; (10) a continuing need for
      clinical material for translational research derived from normal breast, blood,
      primary, relapsed, metastatic and drug-resistant cancers with expert
      bioinformatics support to maximise its utility. The proposed infrastructural
      enablers include enhanced resources to support clinically relevant in vitro and
      in vivo tumour models; improved access to appropriate, fully annotated clinical
      samples; extended biomarker discovery, validation and standardisation; and
      facilitated cross-discipline working. CONCLUSIONS: With resources to conduct
      further high-quality targeted research focusing on the gaps identified, increased
      knowledge translating into improved clinical care should be achievable within
      five years.

PMID- 24286378
TI  - Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.
AB  - OBJECTIVE: The objective of this study was to identify differentially expressed
      salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ)
      patients that could serve as biomarkers for BRONJ diagnosis. SUBJECTS AND
      METHODS: Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled
      within groups. The samples were analyzed using iTRAQ-labeled two-dimensional
      liquid chromatography-tandem mass spectrometry. RESULTS: Overall, 1340 proteins
      were identified. Of these, biomarker candidates were selected based on P-value
      (<0.001), changes in protein expression (>=1.5-fold increase or decrease), and
      unique peptides identified (>=2). Three comparisons made between BRONJ and
      control patients identified 200 proteins to be differentially expressed in BRONJ
      patients. A majority of these proteins were predicted to have a role in drug
      metabolism and immunological and dermatological diseases. Of all the
      differentially expressed proteins, we selected metalloproteinase-9 and
      desmoplakin for further validation. Immunoassays confirmed increased expression
      of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P =
      0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However,
      desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157).
      CONCLUSIONS: Multiple pathological reactions are involved in BRONJ development.
      One or more proteins identified by this study may prove to be useful biomarkers
      for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ
      requires further investigation.

PMID- 24286379
TI  - The effect of smoking cessation on airway inflammation in young asthma patients.
AB  - BACKGROUND: Smoking has been shown to have several detrimental effects on asthma,
      including poor symptom control, attenuated treatment response and accelerated
      decline in lung function. In spite of this, smoking is at least as common among
      asthma patients as in the rest of the population. The aggravations of smoking on
      asthma may be caused by effects on airway inflammation, which has been found to
      be changed in asthmatic smokers. It is not known whether these smoking-induced
      airway inflammation changes are reversible after smoking cessation. OBJECTIVE:
      The aim of this study was to assess airway changes in asthmatic smokers before
      and during smoking cessation. METHODS: Forty-six smokers with asthma, all steroid
      free (age range: 19-40), were recruited. All participants attempted smoking
      cessation over a period of 3 months. Visits were performed at weeks 0, 6 and 12
      and included induced sputum, FeNO, methacholine challenge, lung function, Asthma
      Control Questionnaire (ACQ6) and exhaled CO. RESULTS: Twenty-six of 46 patients
      succeeded in quitting smoking. In the quitters, improvements in methacholine AHR
      (77% before and 52% after smoking cessation, respectively, P = 0.016) and ACQ6
      score (1.7-0.7, P = 0.034) and FeNO (8.7-14.8 p.p.b., P = 0.002) were observed,
      whereas no significant changes were found regarding eosinophils or lung function.
      A small but significant decrease in neutrophils (54.1-52%, P = 0.003) was present
      in quitters compared with the non-quitters. Non-quitters experienced no changes
      in any parameters. CONCLUSION: Smoking cessation improved asthma control, but the
      changes were not related to change in eosinophilic inflammation, and the
      reduction in neutrophils was small. Thus, airway inflammation with eosinophils
      and neutrophils may be less important drivers of asthma control in smokers than
      other factors. CLINICAL RELEVANCE: Smoking cessation may improve clinically
      important disease parameters such as AHR and symptom score, but likely unrelated
      to changes in airway inflammation.

PMID- 24286381
TI  - Replacing the thorough QT study: reflections of a baby in the bath water.

PMID- 24286380
TI  - Progression of coronary artery atherosclerosis in rheumatoid arthritis:
      comparison with participants from the Multi-Ethnic Study of Atherosclerosis.
AB  - INTRODUCTION: In cross-sectional studies, patients with rheumatoid arthritis (RA)
      have higher coronary artery calcium (CAC) than controls. However, their rate of
      progression of CAC and the predictors of CAC progression have heretofore remained
      unknown. METHODS: Incidence and progression of CAC were compared in 155 patients
      with RA and 835 control participants. The association of demographic
      characteristics, traditional cardiovascular risk factors, RA disease
      characteristics and selected inflammatory markers with incidence and progression
      of CAC were evaluated. RESULTS: The incidence rate of newly detected CAC was
      8.2/100 person-years in RA and 7.3/100 person-years in non-RA control subjects
      [IRR 1.1 (0.7-1.8)]. RA patients who developed newly detectable CAC were older
      (59 +/- 7 vs. 55 +/- 6 years old, p=0.03), had higher triglyceride levels (137 +/
      86 vs. 97 +/- 60 mg/dL, p=0.03), and higher systolic blood pressure (129 +/- 17
      vs. 117 +/- 15 mm Hg, p=0.01) compared to those who did not develop incident CAC.
      Differences in blood pressure and triglyceride levels remained significant after
      adjustment for age (p<=0.05). RA patients with any CAC at baseline had a median
      rate of yearly progression of 21 (7-62) compared to 21 (5-70) Agatston units in
      controls. No statistical differences between RA progressors and RA non
      progressors were observed for inflammatory markers or for RA disease
      characteristics. CONCLUSIONS: The incidence and progression of CAC did not differ
      between RA and non-RA participants. In patients with RA, incident CAC was
      associated with older age, higher triglyceride levels, and higher blood pressure,
      but not with inflammatory markers or RA disease characteristics.

PMID- 24286383
TI  - Toxicity evaluation of engineered nanoparticles for medical applications using
      pulmonary epithelial cells.
AB  - There are a multitude of nanoparticles (NPs) which have shown great potentials
      for medical applications. A few of them are already used for lung therapeutic and
      diagnostic purposes. However, there are few toxicological studies which determine
      possible adverse pulmonary responses. It is thus important to propose in vitro
      screening strategies to evaluate the pulmonary toxicity of NPs used in
      nanomedicine. Our goal was to determine the cellular effects of several
      biomedical NPs with different physico-chemical characteristics (chemical nature,
      size and coating) to establish suitable tests and useful benchmark NPs. The
      effects of poly(lactic-co-glycolic acid) (PLGA), silica, iron oxide and titanium
      dioxide NPs were studied using human bronchial (16HBE) and alveolar epithelial
      cells (A549). We evaluated cytotoxicity, reactive oxygen species (ROS) production
      and pro-inflammatory response in both cell lines. We demonstrated that PLGA NPs
      are good candidates for negative control NPs and SiO2 NPs were revealed to be the
      best benchmark NPs. Coating of Fe3O4 with sodium oleate, a known biocompatible
      compound, led to an unexpected increase in cytotoxicity. Moreover, 16HBE cells
      are more sensitive than A549 cells and propidium iodide uptake is a more
      sensitive cytotoxicity test than WST-1. The measurement of oxidative stress does
      not systematically allow us to predict cellular responses and different other
      cellular endpoints should also be addressed. We conclude that a battery of assays
      and cell lines are necessary to accurately evaluate the pulmonary effects of NPs
      and that PLGA and SiO2 NPs are suitable candidates respectively for negative and
      positive controls.

PMID- 24286382
TI  - Association of five genetic variants with chronic obstructive pulmonary disease
      susceptibility and spirometric phenotypes in a Chinese Han population.
AB  - BACKGROUND AND OBJECTIVE: Recent genome-wide association studies have shown
      associations between variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4)
      and chronic obstructive pulmonary disease (COPD) or lung function. However, their
      association with COPD has not been proven in Chinese Han population, nor have
      COPD-related phenotypes been studied. The objective of this study was to look for
      associations between five single nucleotide polymorphisms (SNP) in these novel
      candidate genes and COPD susceptibility or lung function in a Chinese Han
      population. METHODS: Allele and genotype data on 680 COPD patients and 687
      healthy controls for sentinel SNP in these five loci were investigated. Allele
      frequencies and genotype distributions were compared between cases and controls,
      and odds ratios were calculated. Potential relationships between these SNP and
      COPD-related lung function were assessed. RESULTS: No significant associations
      were found between any of the SNP and COPD in cases and controls. The SNP
      (rs3995090) in HTR4 was associated with COPD (adjusted P = 0.022) in never
      smokers, and the SNP (rs2070600) in AGER was associated with forced expiratory
      volume in 1 s (FEV1 %) predicted (beta = -0.066, adjusted P = 0.016) and FEV1
      /forced vital capacity (beta = -0.071, adjusted P = 0.009) in all subjects.
      CONCLUSIONS: The variant at HTR4 was associated with COPD in never-smokers, and
      the SNP in AGER was associated with pulmonary function in a Chinese Han
      population.

PMID- 24286388
TI  - Understanding posttraumatic stress disorder: insights from the methylome.
AB  - Genome-wide association studies (GWAS) have identified numerous disease
      associated variants; however, these variants have a minor effect on disease and
      explain only a small amount of the heritability of complex disorders. The search
      for the missing heritability has shifted attention to rare variants, copy number
      variants, copy neutral variants and epigenetic modifications. The central role of
      epigenetics, and specifically DNA methylation, in disease susceptibility and
      progression has become more apparent in recent years. Epigenetic mechanisms
      facilitate the response to environmental changes and challenges by regulating
      gene expression. This makes the study of DNA methylation in psychiatric disorders
      such as posttraumatic stress disorder (PTSD) highly salient, as the environment
      plays such a vital role in disease aetiology. The epigenome is dynamic and can be
      modulated by numerous factors, including learning and memory, which are important
      in the context of PTSD. Numerous studies have shown the effects of early life
      events, such as maternal separation and traumas during adulthood, on DNA
      methylation patterns and subsequent gene expression profiles. Aberrations in
      adaptive DNA methylation contribute to disease susceptibility when an organism is
      unable to effectively respond to environmental demands. Epigenetic mechanisms are
      also involved in higher order brain functions. Dysregulation of methylation is
      associated with neurodevelopmental and neurodegenerative cognitive disorders,
      affective disorders, addictive behaviours and altered stress responses. A
      thorough understanding of how the environment, methylome and transcriptome
      interact and influence each other in the context of fear and anxiety is integral
      to our understanding and treatment of stress-related disorders such as PTSD. 

PMID- 24286387
TI  - Association of the lipoprotein receptor-related protein 2 gene with gout and non
      additive interaction with alcohol consumption.
AB  - INTRODUCTION: The T allele of a single nucleotide polymorphism (SNP: rs2544390)
      in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum
      urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with
      alcohol consumption in determining hyperuricemia in this population. We
      investigated the association of rs2544390 with gout, and interaction with all
      types of alcohol consumption in European and New Zealand (NZ) Maori and Pacific
      subjects, and a Maori study cohort from the East Coast region of NZ's North
      Island. METHODS: Rs2544390 was genotyped by Taqman(r). From NZ a total of 1205
      controls and 1431 gout cases clinically ascertained were used. Publicly available
      genotype and serum urate data were utilized from the Atherosclerosis Risk in
      Communities (ARIC) study and the Framingham Heart Study (FHS). Alcohol
      consumption data were obtained by consumption frequency questions in all study
      cohorts. Multivariate adjusted logistic regression was done using STATA. RESULTS:
      The T allele of rs2544390 was associated with increased risk of gout in the
      combined Maori and Pacific Island cohort (OR = 1.20, P = 0.009), and associated
      with gout in the European subjects, but with a protective effect (OR = 0.79,
      PUnadjusted = 0.02). Alcohol consumption was positively associated with risk of
      gout in Maori and Pacific subjects (0.2% increased risk/g/week, P = 0.004). There
      was a non-additive interaction between any alcohol intake and the risk of gout in
      the combined Maori and Pacific cohorts (PInteraction = 0.001), where any alcohol
      intake was associated with a 4.18-fold increased risk in the CC genotype group (P
      = 6.6x10-5), compared with a 1.14-fold increased risk in the CT/TT genotype group
      (P = 0.40). These effects were not observed in European subjects. CONCLUSIONS:
      Association of the T-allele with gout risk in the Maori and Pacific subjects was
      consistent with this allele increasing serum urate in Japanese individuals. The
      non-additive interaction in the Maori and Pacific subjects showed that alcohol
      consumption over-rides any protective effect conferred by the CC genotype.
      Further exploration of the mechanism underlying this interaction should generate
      new understanding of the biological role of alcohol in gout, in addition to
      strengthening the evidence base for reduction of alcohol consumption in the
      management of gout.

PMID- 24286389
TI  - Testosterone levels and sexual function disorders in depressive female patients:
      effects of antidepressant treatment.
AB  - INTRODUCTION: Women suffer from depression more frequently than men, which
      indicates that sex hormones might be involved in the etiology of this disease.
      AIMS: The purpose of this study was to assess the relationship between
      testosterone and depression pathophysiology in depressive women along with sexual
      function. We also investigated whether antidepressant treatment causes any change
      in levels of this hormone or in sexual function. METHODS: Premenopausal female
      patients aged 25-46 years (n = 52) with diagnosed major depression were included
      in this study as the patient group, and 25- to 46-year-old premenopausal women
      without depression (n = 30) were included as the control group. MAIN OUTCOME
      MEASURES: Serum testosterone and sex hormone-binding globulin (SHBG) levels were
      measured twice, before and after the antidepressant treatment. Bioavailable
      testosterone (cBT) levels were calculated using the assay results for total
      testosterone (TT), SHBG, and albumin according to the formulas of Vermeulen et
      al. Depression severity was measured using the 17-item Hamilton Depression Rating
      Scale, and sexual function was evaluated with the Arizona Sexual Experience
      Scale. RESULTS: The mean TT and cBT levels significantly increased in the patient
      group after the antidepressant treatment (P < 0.001). Pre-treatment TT and cBT
      levels were significantly lower in the patient group than in the control group (P
      < 0.001). Similar results were obtained for post-treatment serum TT and cBT
      levels in the patient and control groups (P > 0.05). There were no significant
      differences among the groups in terms of SHBG level. CONCLUSION: The low
      testosterone levels in depressed women compared with women in the control group
      and the elevated levels post-pharmacotherapy suggest that testosterone may be
      involved in depression.

PMID- 24286390
TI  - Jasmonate-dependent modifications of the pectin matrix during potato development
      function as a defense mechanism targeted by Dickeya dadantii virulence factors.
AB  - The plant cell wall constitutes an essential protection barrier against pathogen
      attack. In addition, cell-wall disruption leads to accumulation of jasmonates
      (JAs), which are key signaling molecules for activation of plant inducible
      defense responses. However, whether JAs in return modulate the cell-wall
      composition to reinforce this defensive barrier remains unknown. The enzyme 13
      allene oxide synthase (13-AOS) catalyzes the first committed step towards
      biosynthesis of JAs. In potato (Solanum tuberosum), there are two putative St13
      AOS genes, which we show here to be differentially induced upon wounding. We also
      determine that both genes complement an Arabidopsis aos null mutant, indicating
      that they encode functional 13-AOS enzymes. Indeed, transgenic potato plants
      lacking both St13-AOS genes (CoAOS1/2 lines) exhibited a significant reduction of
      JAs, a concomitant decrease in wound-responsive gene activation, and an increased
      severity of soft rot disease symptoms caused by Dickeya dadantii. Intriguingly, a
      hypovirulent D. dadantii pel strain lacking the five major pectate lyases, which
      causes limited tissue maceration on wild-type plants, regained infectivity in
      CoAOS1/2 plants. In line with this, we found differences in pectin methyl
      esterase activity and cell-wall pectin composition between wild-type and CoAOS1/2
      plants. Importantly, wild-type plants had pectins with a lower degree of methyl
      esterification, which are the substrates of the pectate lyases mutated in the pel
      strain. These results suggest that, during development of potato plants, JAs
      mediate modification of the pectin matrix to form a defensive barrier that is
      counteracted by pectinolytic virulence factors from D. dadantii. 

PMID- 24286391
TI  - Cellular and molecular mechanism of ofloxacin induced apoptotic cell death under
      ambient UV-A and sunlight exposure.
AB  - Ofloxacin (OFLX) is a racemic mixture of levofloxacin which revealed
      phototoxicity in patients exposed with sunlight after medication. Here, we have
      been addressed the possible cellular and molecular mechanisms of OFLX induced
      apoptosis under ambient UV-A and sunlight exposure using HaCaT cell line as a
      model. The results showed that Photodegradation and three photo-products
      formation of OFLX by LC-MS/MS under ambient intensities of UV-A (1.5 and 2.2
      mW/cm(2)) and sunlight. OFLX produced (1)O2, O2(.-), and OH radicals via type-II-
      and type-I-dependent reaction mechanism, which corroborated by its specific
      quenchers. 2'-dGua degradation in photochemical and % tail DNA formation in cell
      line using comet test advocated the genotoxic potential of OFLX. Photocytotoxic
      assays (MTT and NRU) revealed the considerable decline in cell viability by OFLX.
      OFLX triggered apoptosis, proved by cell cycle, Annexin V/PI double staining
      along with acridine orange (AO)/ethidium bromide (EB), and Hoechst staining as
      well as caspase-3 activity by colorimetric assay. OFLX induced lysosomal
      disruption and mitochondrial membrane destabilization confirmed through
      fluorescence staining with AO/JC-1. OFLX significantly upregulated the expression
      of p21 and bax genes. In conclusion, the study revealed that photosensitized OFLX
      induced apoptosis via ROS-mediated DNA damage, destabilization of lysosomal and
      mitochondrial membrane, and upregulation of p21, bax, and caspase-3 genes.

PMID- 24286392
TI  - Development, validation and application of an LC-MS/MS bioanalytical method for
      the quantification of GF449, a novel 5-HT1A agonist, in rat plasma and brain.
AB  - We have recently reported a novel class of selective 5-HT1A agonists among which
      GF449 emerged for its high potency and almost full agonist activity (pKi 5-HT1A =
      8.8; pD2 = 9.22, %Emax = 91.6). In order to quantify GF449 in rat plasma and
      brain, a sensitive LC-MS/MS method was developed and validated. Solid phase
      extraction (SPE) or a combined protein precipitation SPE permitted an efficient
      analyte recovery and sample clean-up. Multiple reaction monitoring (MRM) was used
      to track both GF449 and its internal standard (IS), MM189. GF449 was determined
      and quantitated to nanomolar concentrations in both plasma and brain matrix (LOQs
      = 0.0025 nmol/mL). Specificity was ensured using three further MRM qualifier
      transitions for both analyte and IS. Linearity was found in the range of 0.0025
      nmol/mL to 1.00 nmol/mL (R(2) = 0.9965) and from 0.0025 nmol/mL to 50 nmol/mL
      (R(2) = 0.9999) for plasma and brain respectively. Intraday trueness ranged from
      94.0% to 117.5% for brain and from 93.7% to 108.1% for plasma, while precision
      values were within 3.0% - 6.7% and 2.5% - 9.2% for plasma and brain respectively.
      The interday trueness of plasma ranged from 89.6% to 107.7% and the precision
      values (CV%) ranged from 4.6% to 7.5%. Interday trueness and precision (CV%) of
      the brain ranged from 94.3% to 101.2% and from 1.6% to 11.5% respectively. The
      method was validated in accordance with the EMEA guidelines and was successfully
      applied to plasma and brain samples obtained from rats treated with a 10 mg/kg
      single oral dose of GF449, thus demonstrating its applicability to preclinical
      pharmacokinetic studies. 

PMID- 24286393
TI  - Synthesis, pharmacological activity and molecular modeling of 1-aryl-7- hydroxy
      2,3-dihydroimidazo[1,2-a]pyrimidine-5(1H)-ones and their 6-substituted
      derivatives.
AB  - Pain management is an important medical problem with social and economic
      consequences. Opioid receptors are among the most important molecular targets
      involved in antinociception. We have previously reported several series of
      antinociceptive compounds with the affinity to opioid receptors. In search for
      novel compounds acting on central nervous system with antinociceptive activity we
      synthesized a series of 1-aryl-7-hydroxy-2,3-dihydroimidazo[1,2- a]pyrimidine
      5(1H)-ones and their 6-phenyl derivatives. The novel compounds were subjected to
      extensive pharmacological studies to assess their effect on motor coordination,
      body temperature, clonic seizures and tonic convulsions and their antinociceptive
      activity. In the writhing test the antinociceptive activity of some derivatives
      was reversed by naloxone, thus we can assume that their activity may be
      associated with opioid system. We also used molecular modeling to describe active
      conformations of the studied compounds and to build a pharmacophore model. As in
      the previously reported series of the compounds, the studied substances exerted
      antinociceptive activity probably associated with the opioid system without
      possessing a protonable nitrogen atom. Furthermore, we calculated structural,
      electronic and ADMET parameters (volume, surface area, polar surface area,
      ovality, dipole moment, HOMO and LUMO energies, polarizaibility, molar
      refractivity, lipophilicity, the charges on the heteroatoms, aqueous solubility,
      and blood-brain barrier permeation parameter) for novel compounds in order to
      address the observed structure-activity relationship. 

PMID- 24286394
TI  - Discovery of aroyl piperazine derivatives as IKr & IKs dual inhibitors for
      cardiac arrhythmia treatment.
AB  - Combined blockade of IKr and IKs potassium channels is considered to be a
      promising therapeutic strategy for arrhythmia. In this study, we designed and
      synthesized 15 derivatives through modifying the hit compound 7 that was
      discovered by screening in-house database by whole-patch clamp technique. All of
      the compounds were evaluated on CHO and HEK 293 cell lines stably expressing hERG
      (IKr) and hKCNQ1/KCNE1 (IKs) potassium channels, and half of them exhibited
      improved dual IKr and IKs inhibitory effects compared to the hit compound.
      Compounds 7a and 7b with potent dual inhibitory activities were selected for
      further in vivo evaluations. Due to the preferable pharmacological behaviors,
      compound 7a deserved further optimization as a promising lead compound. 

PMID- 24286395
TI  - Discovery of novel CK2 leads by cross-docking based virtual screening.
AB  - Protein kinase CK2, a serine/threonine kinase, is an attractive therapeutic
      target for many diseases. Here we described an application of cross-docking based
      drug design to discover novel and potent CK2 leads. Glide SP was chosen as the
      most suitable docking approach by comparing four docking protocols through native
      docking. Then twenty-four CK2 crystal structures were compared by recovering
      known active ligands from a decoy database to select the optimal ensemble of CK2
      structures, 2PVN, 2ZJW, 3AMY, 3FL5 and 3KXH were severed as the assemble, which
      were used in the virtual screening of compiled SPECS database for small molecules
      inhibiting CK2. Seven compounds were selected and purchased to test the
      biological activity. Compound g (AQ-390/42425635) showed the best inhibition rate
      and the lowest IC50, which can be used as a lead for our subsequent optimization.

PMID- 24286396
TI  - Design and synthesis of quinazolinone derivatives as anti-inflammatory agents:
      pharmacophore modeling and 3D QSAR studies.
AB  - A series of 36 novel substituted quinazolinone derivatives were synthesized and
      evaluated for their antiinflammatory activity by carrageenan induced paw
      inflammation model. The ability of these compounds to inhibit cyclooxygenase (COX
      1 and 2) enzyme has been determined in-vitro; the results indicated that
      quinazolinone derivatives were selective towards COX-2 rather than COX-1. Among
      the quinazolinone derivatives tested, compound 32 showed better inhibition
      against COX-2 when compared with Celecoxib. Pharmacophore modeling and 3D QSAR
      studies were performed in order to elucidate structural insights for the anti
      inflammatory activity. 

PMID- 24286397
TI  - Association between the interleukin-13 gene and development of chronic
      obstructive pulmonary disease in southern Chinese Han population: a case-control
      study.
AB  - BACKGROUND: Interleukin-13 (IL-13) has been implicated to be responsible for
      recruitment of inflammatory cells from the blood to the lung, regulation of
      matrix metalloproteinase and induction of mucin production and secretion in
      chronic obstructive pulmonary disease (COPD). We determined plasma IL-13 levels
      in patients with COPD and investigated its association with common polymorphisms
      of IL-13 gene in a case-control study. METHODS: We genotyped 160 cases and 175
      control subjects in a local hospital using Mass-Array(TM) Technology Platform
      then tested the association of four SNPs in IL-13 (rs1295685, rs1800925,
      rs1881457, rs20541) with COPD, and then determined plasma IL-13 levels in
      patients with COPD and controls. RESULTS: Association was found between IL-13
      gene SNPs (rs20541 and rs1800925) and an increased risk of COPD. By linkage
      disequilibrium (LD) analysis, two blocks (rs1881457 and rs1800925; rs20541 and
      rs1295685) were found. The risk of COPD was found associated with the IL-13 gene
      polymorphism among southern Chinese Han population. Plasma IL-13 level was
      increased in COPD patients compared with controls. CONCLUSIONS: The polymorphism
      of the IL-13 gene is associated with an increased risk of COPD in southern
      Chinese Han population. Plasma IL-13 levels were found elevated in patients with
      COPD.

PMID- 24286399
TI  - Value of a virtual hepatic segment model in assisting in the ultrasonic
      localization of intrahepatic lesions.
AB  - BACKGROUND: During scanning of the right hypochondrium and right intercostal
      regions with an ultrasonic transducer, several ultrasonic images of oblique
      sections are obtained. It is still a challenge for ultrasonography to divide
      these non-conventional sections into an accurate hepatic segmentation pattern.
      The aim of this research was to investigate the value of the virtual hepatic
      segment model (VHSM) in assisting the ultrasonic localization of space-occupying
      hepatic lesions. METHODS: VHSM was constructed via 3D reconstruction according to
      the first Chinese visible human dataset. Preoperative ultrasonography, contrast
      enhanced CT scan and VHSM techniques were performed in 100 patients with space
      occupying focal lesions in the liver parenchyma for segmental localization. The
      results of these three techniques were compared with the operative findings.
      RESULTS: VHSM was successfully detected on 2D sectional images by 3D
      reconstruction through surface rendering and volume rendering. The model could
      simulate ultrasonic directions to conduct a virtual dissection on any section
      plane, and fine liver segmentation could be displayed in any virtual plane. In
      100 patients, there were 112 liver space-occupying focal lesions distributed in
      148 liver segmentations. Regarding the positioning accuracies for lesions of
      different sizes and the lesion segmental distribution accuracies estimated using
      the three methods mentioned above, ultrasonography exhibited a significantly
      lower accuracy than VHSM for the segmental localization of lesions (P < 0.05),
      and contrast-enhanced CT was not significantly different from ultrasonography
      plus VHSM (P > 0.05). CONCLUSION: VHSM increased the accuracy of ultrasonic
      localization of space-occupying hepatic lesions, particularly in hepatic
      hypovascular regions.

PMID- 24286398
TI  - Prevalence, risk factors, clinical course, and outcome of acute kidney injury in
      Chinese intensive care units: a prospective cohort study.
AB  - BACKGROUND: Acute kidney injury (AKI) has been recognized as a major healthcare
      problem affecting millions of patients worldwide. However, epidemiologic data
      concerning AKI in China are still lacking. The objectives of this study were to
      characterize AKI defined by RIFLE criteria, assess the association with hospital
      mortality, and evaluate the impact of AKI in the context of other risk factors.
      METHODS: This prospective multicenter observational study enrolled 3,063
      consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across
      mainland China. We excluded patients who were admitted for less than 24 hours (n
      = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n =
      29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There
      were 1255 patients in the final analysis. AKI was diagnosed and classified
      according to RIFLE criteria. RESULTS: There were 396 patients (31.6%) who had
      AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179
      (14.3%) patients, respectively. Renal function deteriorated in 206 patients
      (16.4%). In comparison with non AKI patients, patients in the risk class on ICU
      admission were more likely to progress to the injury class (odds ratio (OR)
      3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in
      the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR
      13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of
      deteriorating into failure class. The adjusted hazard ratios for 90-day mortality
      were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the
      failure group. CONCLUSIONS: The prevalence of AKI was high among critically ill
      patients in Chinese ICUs. In comparison with non-AKI patients, patients with
      RIFLE class R or class I on ICU admission were more susceptibility to progression
      to class I or class F. The RIFLE criteria were robust and correlated well with
      clinical deterioration and mortality.

PMID- 24286400
TI  - Comparison of low-dose sequences of dual-source CT and echocardiography for
      preoperative evaluation of aortic valve disease.
AB  - BACKGROUND: Accurate evaluation of coronary artery, aortic valve annulus diameter
      (AVAD), and cardiac function in patients with aortic valve disease is of great
      significance for surgical strategy. In this study, we explored the preoperative
      evaluation of low-dose sequence (MinDose sequence) scan of dual-source CT (DSCT)
      for those patients. METHODS: Forty patients suspected for aortic valve disease
      (the experimental group) underwent MinDose sequence of DSCT to observe coronary
      artery, AVAD, and left ventricular ejection fraction (LVEF). Another 33 subjects
      suspected for coronary artery disease (the control group) underwent conventional
      retrospective electrocardiographically-gated sequence of DSCT. Two-dimensional
      transthoracic echocardiography (2D-TTE) and four-dimensional transthoracic
      echocardiography (4D-TTE) were applied in the experimental group to measure AVAD
      and LVEF and compared with MinDose-DSCT. RESULTS: There was a strong correlation
      between LVEFs measured by 2D-TTE and MinDose-DSCT (r = 0.87, P < 0.01), as well
      as between 4D-TTE and MinDose-DSCT (r = 0.90, P < 0.01). AVAD measured by MinDose
      DSCT was in good agreement with corresponding measurements by 2D-TTE (r = 0.90, P
      < 0.01). The effective dose in the experimental group was 63.54% lower than that
      in the control group. CONCLUSIONS: MinDose sequence of DSCT with a low radiation
      dose serving as a one-stop preoperative evaluation makes effective assessment of
      the coronary artery, AVAD, and LVEF for patients with aortic valve disease.

PMID- 24286401
TI  - Relationship among symptoms, mucosal injury, and acid exposure in
      gastroesophageal reflux disease.
AB  - BACKGROUND: Symptoms, endoscopy, and pH monitoring form the basis of diagnosis of
      gastroesophageal reflux disease (GERD). Their relationship was meaningful for
      primary care physicians, but still unclear. Our research aimed to compare
      questionnaire, endoscopy, and pH monitoring and to analyze their correlations.
      METHODS: Three hundred patients who underwent the Reflux Disease Questionnaire
      (RDQ), endoscopy, and esophageal 24-hour pH monitoring from March 2007 to
      December 2010 in Peking University People's Hospital were enrolled. We analyzed
      the characteristics of different investigations and their relationships. RESULTS:
      Male (OR for mild reflux esophagitis (RE) = 2.433, severe RE = 8.386), body mass
      index (BMI) (OR for mild RE = 1.222, severe RE = 1.297), and hernia (OR for mild
      RE = 6.059, severe RE = 17.547), were found to be the risk factors for RE; age
      (OR = 1.074) was correlated with severe RE. The consistency of questionnaire,
      endoscopy, and pH monitoring was poor: RDQ did not agree well with pH monitoring
      (kappa = 0.061), nor with endoscopy (kappa = 0.044); pH monitoring did not agree
      well with endoscopy (kappa = 0.316). However, the severity of mucosa injury in RE
      was associated with pathological acid exposure (PAE): reflux episodes of >5
      minutes (P = 0.035), the percentage time pH <4 (P = 0.017), and the DeMeester
      score (P = 0.016) increased significantly in patients with severe RE. Chest pain
      had poor relationship with RE or PAE. CONCLUSIONS: Male, age, BMI, and hernia
      were probably risk factors for esophagitis. RDQ, endoscopy, and pH monitoring
      have their own focus and reinforce each other in diagnosis. Of the GERD symptoms,
      chest pain had negative correlation with RE or PAE.

PMID- 24286402
TI  - miR-30b and miR-30c expression predicted response to tyrosine kinase inhibitors
      as first line treatment in non-small cell lung cancer.
AB  - BACKGROUND: Aberrantly expressed microRNAs are a hallmark of cancer, and microRNA
      expression profiling is associated with tumor progression and response to
      chemotherapy, suggesting their potential application as prognostic and predictive
      biomarkers. The role of microRNAs in lung cancer remains elusive. It has been
      recently reported that epidermal growth factor receptor (EGFR) and hepatocyte
      growth factor receptor (MET) tyrosine kinase can regulate expression of specific
      microRNAs including miR-30b, miR-30c, miR-221, miR-222, miR-103 and miR-203, and
      induce tumorigenesis and gefitinib resistance in lung cancers. We intend to study
      the role of miR-30b and miR-30c expression in predicting response to tyrosine
      kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). METHODS: We have
      therefore retrospectively examined expression of miR-30b miR-30c in 41 formalin
      fixed paraffin embedded tissue samples from NSCLC patients when TKIs were used as
      first line therapy. RESULTS: We found a significant correlation between
      expression of miR-30b and miR-30c. Furthermore, miR-30b and miR-30c expression
      correlated with short-term response. Kaplan-Meier analysis further revealed that
      the expression of miR-30b and miR-30c predicted progression free survival and the
      overall survival rate in the examined cohort. CONCLUSION: Our study identified
      miR-30b and miR-30c as useful prognostic predictors in NSCLC patients who
      underwent first line treatment with TKIs.

PMID- 24286403
TI  - Bedside chest radiography of novel influenza A (H7N9) virus infections and follow
      up findings after short-time treatment.
AB  - BACKGROUND: Influenza A (H7N9) virus infections were first observed in China in
      March 2013. This type virus can cause severe illness and deaths, the situation
      raises many urgent questions and global public health concerns. Our purpose was
      to investigate bedside chest radiography findings for patients with novel
      influenza A (H7N9) virus infections and the followup appearances after short-time
      treatment. METHODS: Eight hospitalized patients infected with the novel influenza
      A (H7N9) virus were included in our study. All of the patients underwent bedside
      chest radiography after admission, and all had follow-up bedside chest
      radiography during their first ten days, using AXIOM Aristos MX and/or AMX-IV
      portable X-ray units. The exposure dose was generally 90 kV and 5 mAs, and was
      slightly adjusted according to the weight of the patients. The initial
      radiography data were evaluated for radiological patterns (ground glass opacity,
      consolidation, and reticulation), distribution type (focal, multifocal, and
      diffuse), lung zones involved, and appearance at follow-up while the patients
      underwent therapy. RESULTS: All patients presented with bilateral multiple lung
      involvement. Two patients had bilateral diffuse lesions, three patients had
      unilateral diffuse lesions of the right lobe with multifocal lesions of the left
      lobe, and the remaining three had bilateral multifocal lung lesions. The lesions
      were present throughout bilateral lung zones in three patients, the whole right
      lung zone in three patients with additional involvement in the left middle and/or
      lower lung zone(s), both lower and middle lung zones in one patient, and the
      right middle and lower in combination with the left lower lung zones in one
      patient. The most common abnormal radiographic patterns were ground glass opacity
      (8/8), and consolidation (8/8). In three cases examined by CT we also found the
      pattern of reticulation in combination with CT images. Four patients had
      bilateral and four had unilateral pleural effusion. After a short period of
      treatment the pneumonia in one patient had significantly improved and three cases
      demonstrated disease progression. In four cases the severity of the pneumonia
      fluctuated. CONCLUSIONS: In patients with influenza A (H7N9) virus infection, the
      distribution of the lung lesions are extensive, and the disease usually involves
      both lung zones. The most common imaging findings are a mixture of ground glass
      opacity and consolidation. Pleural effusion is common. Most cases have a poor
      short-time treatment response, and seem to have either rapid progressive
      radiographic deterioration or fluctuating radiographic changes. Chest radiography
      is helpful for evaluating patients with severe clinical symptoms and for follow
      up evaluation.

PMID- 24286404
TI  - Association between salivary alpha-amylase activity and pain relief scale scores
      in cancer patients with bone metastases treated with radiotherapy.
AB  - BACKGROUND: Subjective assessment tools such as visual analog scales (VAS) or
      pain scores are commonly used to evaluate the intensity of chronic cancer-induced
      pain. However, their value is limited in some cases. We measured changes in VAS
      pain scores and salivary alpha-amylase (sAA) concentrations in cancer patients
      receiving radiotherapy for bone metastases to ascertain the correlation between
      these measures. METHODS: We enrolled 30 patients with bone metastases attending a
      single institution from June 2010 to March 2011. All patients with cancer-induced
      bone pain received radiation therapy (RT) at the same dose (30 Gy) and
      fractionation (3 Gy/fraction, 5 days/week) for palliative pain relief. We
      assessed heart rate (HR), systolic and diastolic blood pressures (DBP/SBP) and
      VAS pain scores before (d0) and after five (d5) and ten fractions (d10) of
      irradiation. sAA and salivary cortisol (SC) concentrations were measured using a
      portable analyzer and automated chemiluminescence analyzer, respectively.
      RESULTS: Radiotherapy markedly decreased VAS scores from (82.93 +/- 9.29) to
      (31.43 +/- 16.73) mm (P < 0.001) and sAA concentrations from (109.40 +/- 26.38)
      to (36.03 +/- 19.40) U/ml (P <0.001). Moreover, there was a significant
      correlation between these two indices (P <0.01, r = 0.541). HR decreased by 6.5%
      after radiotherapy, but did not correlate with VAS scores (P >0.05). SC
      concentrations and BP did not change significantly during the study (P >0.05).
      CONCLUSIONS: The significant correlation between sAA concentrations and VAS pain
      scores identified in these preliminary results suggests that this biomarker may
      be a valuable, noninvasive and sensitive index for the objective assessment of
      pain intensity in patients with cancer-induced bone pain.

PMID- 24286405
TI  - Differential diagnosis of isolated calf muscle vein thrombosis and gastrocnemius
      hematoma by high-frequency ultrasound.
AB  - BACKGROUND: Differential diagnosis of isolated calf muscle vein thrombosis
      (ICMVT) and gastrocnemius hematoma is essential for early identification of deep
      vein thrombosis (DVT). This study aimed to investigate the diagnostic value of
      high-frequency color Doppler ultrasound for differential diagnosis of ICMVT and
      gastrocnemius hematoma. METHODS: A retrospective case series of 35 ICMVT (M:F,
      21:14; mean age (64.5 +/- 10.6) years) and 23 gastrocnemius hematoma (M:F, 16:7;
      mean age (75.4 +/- 11.8) years) patients with bilateral/unilateral lower limb
      pain was conducted between January 2006 and September 2012. Characteristics and
      the morphology of high-frequency color Doppler ultrasonography of the lower limb
      deep vein, great saphenous vein, calf muscles, skin, and soft tissue were
      examined. RESULTS: ICMVT hypoechoic signals were characterized by long, tube-like
      masses on longitudinal sections and oval masses on transverse sections, with
      apparent muscle thrombosis boundaries, distal and proximal venous connections,
      and, often, lower limb DVT. Gastrocnemius hematoma hypoechoic signals were
      characterized by large volumes, enhanced posterior hematoma echo, hyperechoic
      muscle boundaries, no hematoma blood flow, and no DVT, and clear differences in
      trauma/exercise- and oral anticoagulant-induced hematomas were readily apparent.
      According to the measurement, the ratio of long diameter/transverse diameter
      (D/T) in ICMVT patients was about less than 2.0, whereas in gastrocnemius
      hematoma patients the ratio was more than 2.0. Early stage isoechoic and
      hypoechoic signals were detected with gradually increasing ovular anechoic areas.
      Partial muscle fibers in the hematoma due to muscle fractures were apparent.
      CONCLUSION: High-frequency color Doppler ultrasound was found to be a sensitive
      and reliable method for differential diagnosis of ICMVT and gastrocnemius
      hematoma due to trauma and exercise or prolonged oral anticoagulant use.

PMID- 24286406
TI  - Diagnostic value of endobronchial ultrasound guided transbronchial needle
      aspiration in superior vena cava syndrome.
AB  - BACKGROUND: The pathological diagnosis is of critical importance to the
      subsequent treatment for the pathients with superior vena cava syndrome (SVCS).
      The aim of this study is to report our experience in the diagnosis of SVCS by
      endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA).
      METHODS: The data of 520 patients who underwent EBUS-TBNA from September 2009 to
      May 2012 at our institution were reviewed. Of these, there were 14 males and 6
      females (mean age of 59.1 years) with SVCS who received EBUS-TBNA that were
      included in the analysis. RESULTS: The mean short axis diameter of the
      paratracheal lesions was (3.32 +/- 1.79) cm (range, 1.69 to 9.50 cm) and 6 cases
      also had subcarinal lymph node enlargement with a mean short axis diameter of
      (2.14 +/- 0.49) cm (range, 1.73 to 3.01 cm). An average of 4.3 punctures was
      performed per lesion. Malignancy was confirmed in 16 cases (10 small cell
      carcinomas, 4 adenocarcinomas, 1 squamous cell carcinoma and 1 Hodgkin lymphoma).
      In two patients, pathological examination of tissue revealed no evidence of
      malignancy and for 13 to 24 months of follow-up. One patient from whom adequate
      tissue was not obtained refused further surgical biopsy since he had undergone
      endovascular stenting of the SVC. One patient in whom a diagnosis was not
      obtained by EBUS-TBNA underwent thoracoscopic biopsy and the final diagnosis was
      B cell non-Hodgkin's lymphoma. The diagnosis accuracy of EBUS-TBNA in SVCS was
      18/20 patients. CONCLUSION: EBUS-TBNA is a highly effective and safe procedure
      for the diagnosis of SVCS.

PMID- 24286407
TI  - Evaluation of the asynchronization and function of the left ventricle in patients
      with chronic pulmonary hypertension by velocity vector imaging.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a set of pathophysiological syndromes
      characterized by increased pulmonary artery pressure and pulmonary vascular
      resistance, resulting in increased right ventricular afterload. The left and
      right ventricles interact through hemodynamics. What impact will PH have on
      synchronization and function of the left ventricle (LV)? The aim of this study
      was to evaluate the synchronization of the left ventricular wall motion and left
      ventricular function in patients with varying degrees of PH using velocity vector
      imaging (VVI) technology. METHODS: Sixty patients with chronic PH served as the
      experimental group, and 20 healthy volunteers served as the control group.
      According to the different degrees of pulmonary artery systolic pressure, the
      experimental group was divided into three groups: mild, moderate, and severe PH
      groups. The time to peak systolic longitudinal velocity (Tvl), the peak systolic
      longitudinal velocity (Vsl), the peak diastolic longitudinal velocity (Vel), the
      peak systolic longitudinal strain (Sl), and strain rate (SRl) in 18 segments were
      measured in each group. RESULTS: Tvl in the control group and each group with PH
      was reduced from basal to apical segment, and in control group Tvl in various
      segments of the same wall and in different walls showed no significant difference
      (P > 0.05). With increase in pulmonary artery pressure, Tvl values measured
      showed an increasing trend in groups with PH. In groups with PH, Vsl and Vel of
      each wall were reduced sequentially from basal to apical segments, showing
      gradient change; Vsl and Vel values measured showed a decreasing trend with
      increase in pulmonary artery pressure, in which the differences of Vel values
      measured in the control group and the mild PH group were statistically
      significant (P < 0.01), and the differences between other groups were
      statistically significant (P < 0.01). In groups with PH, Sl and SRl in basal
      segment and the middle segment of each wall were decreased; the difference
      between groups was statistically significant (P < 0.01). CONCLUSIONS:
      Asynchronization of the LV and decreased left ventricular function were present
      in patients with chronic PH; VVI technology can accurately evaluate left
      ventricular function in patients with PH, and indicators such as Tvl, Vsl, and
      Vel are valuable.

PMID- 24286408
TI  - Efficacy and safety of noninvasive positive pressure ventilation in the treatment
      of acute respiratory failure after cardiac surgery.
AB  - BACKGROUND: Although noninvasive positive pressure ventilation (NPPV) has been
      successfully used for various kinds of acute respiratory failure, the data are
      limited regarding its application in postoperative respiratory failure after
      cardiac surgery. Therefore, we conducted a prospective randomized control study
      in a university surgical intensive care unit to evaluate the efficacy and safety
      of NPPV in the treatment of acute respiratory failure after cardiac surgery, and
      explore the predicting factors of NPPV failure. METHODS: From September 2011 to
      November 2012 patients with acute respiratory failure after cardiac surgery who
      had indication for the use of NPPV were randomly divided into a NPPV treatment
      group (NPPV group) and the conventional treatment group (control group). The
      between-group differences in the patients' baseline characteristics, re
      intubation rate, tracheotomy rate, ventilator associated pneumonia (VAP)
      incidence, in-hospital mortality, mechanical ventilation time after enrollment
      (MV time), intensive care unit (ICU) and postoperative hospital stays were
      compared. The factors that predict NPPV failure were analyzed. RESULTS: During
      the study period, a total of 139 patients who had acute respiratory failure after
      cardiac surgery were recorded, and 95 of them met the inclusion criteria, which
      included 59 males and 36 females with a mean age of (61.5 +/- 11.2) years. Forty
      three patients underwent coronary artery bypass grafting (CABG), 23 underwent
      valve surgery, 13 underwent CABG+valve surgery, 13 underwent major vascular
      surgery, and three underwent other surgeries. The NPPV group had 48 patients and
      the control group had 47 patients. In the NPPV group, the re-intubation rate was
      18.8%, tracheotomy rate was 12.5%, VAP incidence was 0, and the in-hospital
      mortality was 18.8%, significantly lower than in the control group 80.9%, 29.8%,
      17.0% and 38.3% respectively, P < 0.05 or P < 0.01. The MV time and ICU stay
      (expressed as the median (P25, P75)) were 18.0 (9.2, 35.0) hours and 4.0 (2.0,
      5.0) days, which were significantly shorter than in the control group, 96.0
      (26.0, 240.0) hours and 6.0 (4.0, 9.0) days respectively, P < 0.05 or P < 0.01.
      The postoperative hospital stays of the two groups were similar. The univariate
      analysis showed that the NPPV success subgroup had more patients with acute lung
      injury (ALI) (17 vs. 0, P = 0.038), fewer patients with pneumonia (2 vs. 7, P <
      0.001) and lower acute physiology and chronic health evaluation II (APACHE II)
      scores (16.1 +/- 2.8 vs. 21.8 +/- 3.2, P < 0.001). Multivariate analysis showed
      that pneumonia (P = 0.027) and a high APACHE II score >20 (P = 0.002) were the
      independent risk factors of NPPV failure. CONCLUSIONS: We conclude that NPPV can
      be applied in selected patients with acute respiratory failure after cardiac
      surgery to reduce the need of re-intubation and improve clinical outcome as
      compared with conventional treatment. Pneumonia and a high APACHE II score >20
      might be the independent risk factors of NPPV failure in this group of patients.

PMID- 24286409
TI  - Large and giant medial sphenoid wing meningiomas involving vascular structures:
      clinical features and management experience in 53 patients.
AB  - BACKGROUND: Large and giant medial sphenoid wing meningiomas that are located
      deeply in the skull base where they are closely bounded by cavernous sinus, optic
      nerve, and internal carotid artery make the gross resection hard to achieve.
      Also, this kind of meningiomas is often accompanied by a series of severe
      complications. Therefore, it was regarded as a formidable challenge to even the
      most experienced neurosurgeons. This study aimed to investigate the clinical
      features and management experience of patients with large and giant medial
      sphenoid wing meningiomas. METHODS: In this study, 53 patients (33 female and 20
      male, mean age of 47.5 years) with large and giant medial sphenoid wing
      meningiomas were treated surgically between April 2004 to March 2012, with their
      clinical features analyzed, management experience collected, and treatment
      results investigated retrospectively. RESULTS: In this study, gross total
      resection (Simpson I and II) was applied in 44 patients (83%). Fifty-three
      patients had accepted the routine computed tomography scan and magnetic resonance
      imaging scan as postoperative neuroradiological evaluation. Their performance
      showed surgical complications of vascular lesions and helped us evaluate
      patients' conditions, respectively. Meanwhile, the drugs resisting cerebral
      angiospasm, such as Nimodipine, were infused in every postoperative patient
      through vein as routine. As a result, 11 patients (21%) were found to have
      secondary injury of cranial nerves II, III, and IV, and nine patients got
      recovered during the long-term observing follow-up period. Temporary surgical
      complications of vascular lesions occurred after surgery, such as cerebral
      angiospasm, ischemia, and edema; 24 patients (45%) appeared to have infarction
      and dyskinesia of limbs. Overall, visual ability was improved in 41 patients
      (77%). No patient died during the process. CONCLUSIONS: Microsurgical treatment
      may be the most effective method for the large and giant medial sphenoid wing
      meningiomas. The surgical strategy should focus on survival and postoperative
      living quality.

PMID- 24286410
TI  - Oxaliplatin-based combination chemotherapy is still effective for the treatment
      of recurrent and platinum-resistant epithelial ovarian cancer: results from a
      single center.
AB  - BACKGROUND: Combination paclitaxel and carboplatin is currently a first-line
      regimen for ovarian cancer. However, many patients develop tumor recurrence or
      drug resistance to this regimen. The study aims to investigate the effectiveness
      and safety of an oxaliplatin + epirubicin + ifosfamide regimen for the treatment
      of recurrent and drug-resistant epithelial ovarian cancer. METHODS: A
      retrospective analysis of 73 patients with recurrent and drug-resistant ovarian
      cancer was performed; 38 cases of them received oxaliplatin + epirubicin +
      ifosfamide regimens (IAP group), 35 patients received non-oxaliplatinbased
      chemotherapy regimens (control group). The therapeutic effects and side effects
      of the oxaliplatin + epirubicin + ifosfamide regimen were analyzed and
      summarized. Kaplan-Meier survival curves and Cox proportional hazards regression
      were used to compare progression-free and overall survival between the two
      groups. RESULTS: Of the 38 patients in the IAP group, 14 patients (36.84%)
      achieved complete remission, 12 (31.58%) achieved partial remission, 2 (5.26%)
      achieved stable disease and 10 (26.32%) developed progressive disease. The
      overall effective rate (complete or partial remission) of the IAP regime was
      68.42%. While, of the 35 patients in the control group, 12 patients (34.29%)
      achieved complete remission, 3 (8.57%) achieved partial remission, 5 (14.29%)
      achieved stable disease and 15 (42.86%) developed progressive disease. The
      overall effective rate was 42.86%, which was lower than that in the IAP group (P
      = 0.035, chi(2) = 4.836). Progression-free survival was 9.5 months (0-64 months)
      in the IAP group vs. 3 months (0-74 months) in the non-oxaliplatin group (P =
      0.014 by Kaplan-Meier survival curves; HR = 2.260; 95%CI 1.117-4.573; P = 0.023
      by Cox proportional hazards regression). Median overall survival was 46 months (9
      124 months) in the IAP group vs. 35 months (9-108 months) in non-oxaliplatin
      group (P = 0.018 by Kaplan-Meier survival curves; HR = 2.272; 95%CI 1.123-4.598;
      P = 0.022 by Cox proportional hazards regression). In IAP group, 15.79% (6/38) of
      the patients suffered grade III-IV bone marrow arrest. The main non-hematological
      side effects of the IAP regimen included nausea and vomiting (21.05%, 8/38),
      peripheral neurotoxicity (15.79%, 6/38) and hepatic or renal lesions (2.63%,
      1/38). The main side effects of the two chemotherapy regimens showed no
      statistical difference. CONCLUSION: The oxaliplatin-based IAP regimen is
      potentially effective for salvage chemotherapy in patients with recurrent and
      drug-resistant ovarian cancer, with a better therapeutic effect and tolerable
      side effects.

PMID- 24286411
TI  - Diagnosis of Fanconi anemia in children with atypical clinical features: a
      primary study.
AB  - BACKGROUND: Fanconi anemia is a severe congenital disorder associated with
      mutations in a cluster of genes responsible for DNA repair. Arriving at an
      accurate and timely diagnosis can be difficult in cases of Fanconi anemia with
      atypical clinical features. It is very important to increase the rate of accurate
      diagnosis for such cases in a clinical setting. The purpose of this study is to
      explore the clinical diagnosis of Fanconi anemia in children with atypical
      clinical features. METHODS: Six cases of Fanconi anemia with atypical clinical
      features were enrolled in the study, and their clinical features were recorded,
      their FANCA gene transcription was assessed by RT-PCR, and FANCA mutations and
      the ubiquitination of FANCD2 protein were analyzed using DNA sequencing and
      western blotting respectively. RESULTS: All six cases showed atypical clinical
      features including no apparent deformities, lack of response to immune therapy,
      and progressively increasing bone marrow failure. They also have significantly
      increased fetal hemoglobin, negative mitomycin-induced fracture test results, and
      carry a FANCA gene missense mutation. Single protein ubiquitination of FANCD2 was
      not observed in those patients. CONCLUSION: The combination of clinical features,
      FANCA pathogenic gene mutation genotype and the absence of FANCD2 protein
      ubiquitination are helpful in the accurate and timely diagnosis of Fanconi anemia
      in children.

PMID- 24286412
TI  - Clinical characteristics of 4355 patients with anterior cruciate ligament injury.
AB  - BACKGROUND: Clinical features of anterior cruciate ligament (ACL) injury are
      important for its prevention, diagnosis and treatment. However, few studies have
      reported such data, especially in China. The purpose of this study was to
      describe the clinical characteristics of ACL injury on a large cohort. METHODS:
      Between 1993 and 2007, a total of 4355 ACL deficient inpatients (612 athletes and
      3743 non-athletes) were registered. Data were collected using a special database
      system. And the distributions of characteristics in different groups were
      compared and analyzed statistically. RESULTS: All subjects were confirmed with
      ACL tear during surgery. Statistical analysis revealed that the percentage of
      females in Athlete Group was significantly higher than that in Non-athlete Group
      (56.05% vs. 24.95%, P < 0.001). This study also found that sports trauma was the
      main cause of ACL tears. Soccer, basketball, judo, wrestling and track and field
      were the five most responsible activities for athletes. The average injury time
      for athletes was significantly shorter than that for non-athletes (413.3 days vs.
      717.5 days, P < 0.001). Three thousand nine hundred and eight cases were ordered
      ACL reconstruction (76.04% single-bundle, 18.30% double-bundle). Three hundred
      and forty-five patients (7.92%) were combined with other ligaments injuries, 2667
      (61.24%) were found with various grades of cartilage lesions, and 3377 (77.54%)
      were found with meniscal injury. CONCLUSIONS: Sports trauma was the main cause of
      ACL tears in China, and reconstruction had become the principal surgical choice.
      In order to restore knee joint stability and reduce the incidence of cartilage
      and meniscal injury, patienttailored ACL reconstruction should be suggested at
      the right moment.

PMID- 24286413
TI  - Analysis of Graves' ophthalmopathy patients' tear protein spectrum.
AB  - BACKGROUND: Graves' ophthalmopathy/orbitopathy (GO) patients often suffer ocular
      surface damages and tear fluid proteins play a significant role in maintaining
      healthy ocular surfaces, while changes in tear protein components reflect the
      changes ocular surface abnormalities. In this study proteomics techniques were
      used to investigate tear protein compositions in GO patients. METHODS: We carried
      out a case-control study by comparing tear fluid contents of GO patients with
      that of healthy subjects. In the first step the tears were subjected to SDS-PAGE
      electrophoresis and then single protein bands were analyzed by to in-gel trypsin
      digestion and nano-flow liquid mass spectrometry (LC-MS/MS) using a MS software.
      RESULTS: In tear samples of GO subjects, the protein fractions of inflammation
      related protein immunoglobulin kappa chain C region (IgKC) and serum albumin were
      essentially reduced, whereas a novel isoform of complement component 3 (C3),
      which we detected in control subjects, was completely absent in the GO patients'
      tears. CONCLUSIONS: Reduced protein concentrations of particularly IgKC and
      complement C3 as well as albumin in the tears of GO patients may contribute to
      changes in their ocular surfaces via diminished reactive oxygen species (ROS)
      depletion and adaptive immune responses. The completely absent of C3 in the GO
      patients' tears, may imply that an important inflammatory signaling pathway is
      affected, which needs further investigation.

PMID- 24286414
TI  - Application of the multi-planar reconstruction in endovascular treatment of type
      B aortic dissection.
AB  - BACKGROUND: Although Multi-planar reconstruction (MPR) has been considered a
      diagnostic imaging technique that observes more perspectives for diseases, few
      people have applied it surgically. In fact, MPR is also very useful to clinical
      operation, especially for patients with type B aortic dissection. It helps the
      surgeon to locate accurately with more information about aortic dissection, so
      that the safety and effectiveness of operation can be improved. This study
      examined the application of the MPR in intraoperative DSA imaging for precise
      positioning by accurately obtaining a cross-section, a spin angle of the coronal
      plane, and a tilt angle of the sagittal plane in treatment of type B aortic
      dissection. METHODS: The conventional and the MPR approaches were compared on
      positioning the aortic arch for surgery. A group of 40 patients (group A) and
      another group of 42 patients (group B) was sampled. About the comparison of
      baseline characteristics, a fourfold table chi(2) test was conducted on gender,
      and two independent samples t-test was applied to age between group A and group
      B. Spin as well as tilt angles for group A were obtained from the patients using
      both approaches, and their effectiveness was compared with pair t-tests; The MPR
      data guided stent-grafting in this group. Stent graft placement of group B was
      based on the conventional approach. Percentages of proximal distributed markers
      as well as incidences of complications were collected from both groups after
      stent graft placement. They were also compared with a fourfold table chi(2) test.
      RESULTS: Gender difference was not found between group A and group B (chi(2)0.80,
      P > 0.05), and age difference was not statistically significant (F = 2.55,
      homogeneity of variance, t = -1.46, P > 0.05). A significant difference was found
      between the conventional and the MPR approaches for spin angle (t = 9.17) as well
      as tilt angle (t = 2.07), P < 0.05. Percentage of proximal distributed markers
      (5.0%) of group A was significantly lower than that of group B (42.9%), chi(2) =
      15.92, P < 0.05; and incidence of complications (5.0%) of group A was also
      significant lower than that of group B (21.4%), chi(2) = 4.76, P < 0.05.
      CONCLUSIONS: Application of the MPR facilitated intraoperative angle adaption and
      led to satisfactory DSA. It is feasible in endovascular treatment of type B
      aortic dissection, and can effectively and safely guide surgical operations.

PMID- 24286415
TI  - Proactive infection control measures to prevent nosocomial transmission of
      carbapenem-resistant Enterobacteriaceae in a non-endemic area.
AB  - BACKGROUND: Identification of hospitalized carbapenem-resistant
      Enterobacteriaceae (CRE)-positive patient is important in preventing nosocomial
      transmission. The objective of this study was to illustrate the implementation of
      proactive infection control measures in preventing nosocomial transmission of CRE
      in a healthcare region of over 3200 beds in Hong Kong between October 1, 2010 and
      December 31, 2011. METHODS: The program included active surveillance culture in
      patients with history of medical tourism with hospitalization and surgical
      operation outside Hong Kong within 12 months before admission, and "added test"
      as an opportunistic CRE screening in all fecal specimens submitted to the
      laboratory. Outbreak investigation and contact tracing were conducted for CRE
      positive patients. Serial quantitative culture was performed on CRE-positive
      patients and the duration of fecal carriage of CRE was analyzed. RESULTS: During
      the study period, a total of 6533 patients were screened for CRE, of which 76
      patients were positive (10 from active surveillance culture, 65 from "added
      test", and 1 secondary case from contact tracing of 223 patients with no
      nosocomial outbreak), resulting in an overall rate of CRE fecal carriage of 1.2%.
      The median time of fecal carriage of CRE was 43 days (range, 13-119 days). Beta
      lactam-beta-lactamase-inhibitors, cephalosporins, and fluoroquinolones were
      associated significantly with high fecal bacterial load when used 90 days before
      CRE detection, while use of cephalosporins, carbapenems, and fluoroquinolones
      after CRE detection are significantly associated with longer duration of
      carriage. The duration of fecal carriage of CRE also correlates significantly
      with the initial fecal bacterial load (Pearson correlation: 0.53; P = 0.02).
      CONCLUSION: Proactive infection control measures by enhanced surveillance program
      identify CRE-positive patients and data obtained are useful for the planning of
      and resource allocation for CRE control.

PMID- 24286416
TI  - Altered miR-143 and miR-150 expressions in peripheral blood mononuclear cells for
      diagnosis of non-small cell lung cancer.
AB  - BACKGROUND: Sensitive and specific biomarkers for identifying early stage of non
      small cell lung cancer (NSCLC) are urgently needed to improve the therapeutic
      outcome and reduce the mortality. Small non-coding microRNAs (miRNAs) are key
      components of cancer development and are considered as potential biomarkers for
      cancer diagnosis and for monitoring treatment. The aim of this study was to
      determine whether aberrant miRNA expression can be used as a marker in peripheral
      blood mononuclear cells (PBMC) for the diagnosis of NSCLC. METHODS: The levels of
      two mature miRNAs (miR-143 and miR-150) were detected by probe-based stem-loop
      quantitative reverse-transcriptase PCR (RT-qPCR) in PBMC of 64 patients with
      NSCLC and 26 healthy individuals, and the relationship between miR-143 and miR
      150 levels and clinical and pathological factors was explored. RESULTS: All
      endogenous miRNAs were present in peripheral blood in a remarkably stable form
      and detected by RT-qPCR. MiR-143 expression in the PBMC specimens was
      significantly lower in NSCLC patients than in healthy individuals (P < 0.0001).
      MiR-150 expression in the PBMC specimens was not significantly different between
      NSCLC patients and healthy individuals (P = 0.260). MiR-150 expression was
      significantly higher in lung adenocarcinoma patients than in healthy individuals
      (P = 0.001). There was a very strong difference in the expression level of miR
      150 between lung adenocarcinoma patients and lung squamous cell carcinoma
      patients (P < 0.0001). In receiver operating characteristic curve (ROC) analysis,
      low expression of miR-143 showed the area under the ROC (AUC) of 0.885 for
      distinguishing cancer patients from healthy subjects. High expression of miR-150
      had an AUC of 0.834 for distinguishing lung adenocarcinoma patients from healthy
      subjects. High expression of miR-150 had an AUC of 0.951 for distinguishing lung
      adenocarcinoma from lung squamous cell carcinoma. The miR-150 level was
      significantly associated with distant metastasis (P = 0.014). CONCLUSIONS: It is
      indicated that there is a potential for using miR-143 as a novel diagnostic
      biomarker for NSCLC. Moreover, miR-150 can be a highly accurate marker for
      differentiating adenocarcinoma from squamous cell carcinoma.

PMID- 24286417
TI  - Role of endoplasmic reticular stress in aortic endothelial apoptosis induced by
      intermittent/persistent hypoxia.
AB  - BACKGROUND: Accumulated evidence shows that hypoxia can induce endothelial
      apoptosis, however the mechanism is still unknown. We hypothesized whether
      intermittent or persistent hypoxia could induce endoplasmic reticular stress,
      leading to endothelial apoptosis. METHODS: Twenty-four 8-week male Sprague Dawley
      (SD) rats were divided into three groups: normoxia (NC) group, intermittent
      hypoxia (IH) group and persistent hypoxia (PH) group. TUNEL staining was
      performed to detect aortic arch endotheliar apoptosis, and immunohistochemistry
      for BIP, CHOP and caspase12 to test protein expression; human umbilical vein
      endothelial cells (HUVECs) of the line ECV304 were cultured (with or without
      taurodeoxycholic acid (TUDCA) 10 mmol/L, 100 mmol/L) and divided into four
      groups: NC group (20.8% O2 for 4 hours), PH1 group (5% O2 for 4 hours), PH2 group
      (5% O2 for 12 hours) and IH group (20.8% O2 and 5% O2 alternatively for 8 hours).
      Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to
      assess apoptosis in each group. The expressions of GRP78, CHOP and caspase12 were
      detected by real-time quantitative reverse-transcription PCR. Result Intermittent
      and persistent hypoxia could increase the rate of endothelium apoptosis and the
      expressions of GRP78, CHOP and caspase12 compared with the control, induction by
      intermittent hypoxia was slightly higher than persistent hypoxia. In the HUVEC
      experiment, TUDCA significantly reduced apoptosis and the expressions of GRP78,
      CHOP and caspase12. CONCLUSION: Hypoxia, especially intermittent, can induce
      endothelial cell apoptosis possibly through endoplasmic reticulum stress pathway,
      which can be attenuated by taurodeoxycholic acid.

PMID- 24286418
TI  - Expression of hepatocyte growth factor and its receptor c-Met in lens-induced
      myopia in guinea pigs.
AB  - BACKGROUND: Myopia is a common disorder and the incidence has increased yearly,
      but its pathogenesis remains unclear. The aim of this study was to investigate
      the possible role of hepatocyte growth factor (HGF) and its receptor c-Met in the
      development of lens-induced myopia in guinea pigs. METHODS: Sixty one-week-old
      guinea pigs were chosen. The right eyes were treated with -10.0 diopters (D)
      lenses as the lens-induced myopia group; the left eyes remained untreated as the
      control group. Six weeks later, refractive status and axial length were
      determined by streak retinoscopy and A-scan ultrasonography, respectively. The
      guinea pigs were killed and both eyes collected. Morphological changes were
      observed by hematoxylin and eosin staining. The expression levels of HGF, c-Met,
      and matrix metalloproteinase 2 (MMP-2) mRNA and protein in the posterior sclera
      were analyzed by RT-PCR and Western blotting, respectively. RESULTS: The lens
      induced myopia group became myopic with a significant increase in axial length
      and a significant decrease in refraction. Compared with the control group, the
      posterior retina and sclera were thinner in the lens-induced myopia group. The
      expression levels of HGF and MMP-2 mRNA and protein and of phosphorylated c-Met
      protein were significantly higher in the posterior sclera of the lens-induced
      myopia group than in the control group (all P < 0.05). In the lens-induced myopia
      group, the expression level of MMP-2 in the posterior sclera positively
      correlated with the expression level of HGF (r = 0.902, P < 0.05) and
      phosphorylated c-Met (r = 0.885, P < 0.05). CONCLUSION: HGF/c-Met might play a
      role in the development of lens-induced myopia in guinea pigs by upregulating the
      expression of MMP-2.

PMID- 24286419
TI  - Effect of poly(DL-lactide-co-glycolide) on scar formation after glaucoma
      filtration surgery.
AB  - BACKGROUND: Glaucoma filtering surgery (GFS) is the most common procedure
      performed in the treatment of glaucoma. Although antiscarring agents help prevent
      postsurgical scarring and improve glaucoma surgical outcomes, they may be
      associated with an increased incidence of severe and potentially blinding
      complications. Poly(DL-lactide-co-glycolide) (PDLLA/GA) is a bioresorbable
      polymer, which can be prepared with a large range of physical, mechanical, and
      biological properties and has been widely used in medicine, including as an
      absorbable suture and a drug carrier and especially as a scaffold in tissue
      engineering. This study aimed to evaluate the effect of PDLLA/GA on scar
      formation after glaucoma filtration surgery (GFS). METHODS: Forty-eight New
      Zealand white rabbits were divided into two groups randomly and GFS was performed
      on the right eye of each. PDLLA/GA membranes were put under the sclera flap for
      evaluation. GFS with no membrane inserted served as control. Clinical evaluations
      of intraocular pressure (IOP) and the presence of a filtration bleb were
      performed at intervals (3 days, 1, 2, 4, 8, 12, 20, and 24 weeks)
      postoperatively. At each time point, three eyes per group were excised to observe
      histological changes such as inflammation and scar formation and the expression
      of collagen type IV, proliferating cell nuclear antigen (PCNA), matrix
      metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP
      1). The expression of connective tissue growth factor (CTGF) mRNA was determined
      by reverse transcription-polymerase chain reaction. RESULTS: The lower IOP level
      and an effective bleb were maintained for a long time after GFS in the PDLLA/GA
      group. The histological analysis showed less inflammation and scar formation,
      weaker expression of collagen type IV and PCNA, more intense MMP-9 and TIMP-1,
      slightly elevated ratio of MMP-9 and TIMP-1, and a smaller increase in CTGF mRNA
      postoperatively in the PDLLA/GA group but less than the control group (P < 0.05).
      CONCLUSION: PDLLA/GA membranes may be promising for preventing fibrosis after
      GFS.

PMID- 24286420
TI  - Novel agent for Helicobacter pylori infection management.

PMID- 24286421
TI  - Effect of partial liquid ventilation on lung function in oleic acid-induced lung
      injury model of piglets.
AB  - BACKGROUND: Pediatric patients are susceptible to lung injury that does not
      respond to traditional therapies. Partial liquid ventilation (PLV) has been
      developed as an alternative ventilatory strategy for treating severe lung injury.
      The aim of this study is to investigate the effect of PLV on lung function in
      immature piglets. METHODS: Acute lung injury was induced in 12 Chinese immature
      piglets by oleic acid (OA). The animals were randomly assigned to two groups (n =
      6 each group): (1) conventional mechanical ventilation (MV) group and (2) PLV
      with FC-77 (10 ml/kg) group. Mean arterial blood pressure (MAP), mean pulmonary
      arterial pressure (MPAP), central venous pressure (CVP), left atrial pressure
      (LAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR),
      cardiac output (CO), mean pressure of airway (Paw), dynamic lung compliance
      (Cydn), and arterial blood gases were measured during the observation period.
      RESULTS: No piglet died in either group with severe lung injury. After four hours
      of ventilation, pH in the MV group gradually decreased to lower than 7.20, while
      in the PLV group, pH also gradually decreased but remained higher than 7.20 (P <
      0.05). Partial pressure of oxygen in artery (PaO2) decreased in both groups, but
      with a significant difference between the PLV group and MV group (P < 0.05).
      Partial pressure of carbon dioxide in artery (PaCO2) increased in both groups,
      but with a significant difference between the PLV group and MV group (P < 0.05).
      Paw increased in both groups, but was not significantly different (P > 0.05).
      Cydn decreased in both groups, but without a significant difference (P > 0.05).
      At four hours, heart rate (HR) and MAP in both groups decreased. MPAP in both
      groups increased, and there was a significant difference between the two groups
      (P < 0.05). CVP was stable in both groups. At four hours, PVR and LAP were
      increased in both groups. CO was decreased in both groups (P < 0.05). SVR was
      stable during the observation time. CONCLUSION: PLV did not improve outcome in
      changes of lung function.

PMID- 24286422
TI  - An in vivo model of in situ implantation using pulmonary valved conduit in large
      animals under off-pump condition.
AB  - BACKGROUND: The application of pulmonary valved conduit to reconstruct the
      continuity between right ventricles and pulmonary artery is one of the major
      surgeries. This study aimed to establish an in vivo model of in situ implantation
      using pulmonary valved conduit in large animals under off-pump condition to
      validate the long-term effects of artificial pulmonary valved conduit. METHODS:
      Domesticate juvenile male sheep and tissue-engineered porcine pulmonary valved
      conduit were used for the experiment: 30 sheep, weighing (15 +/- 3) kg (range 13
      to 17 kg) were randomly divided into two groups which were all operated under
      general anesthesia by off-pump surgery (group 1) and left thoracotomy (group 2).
      Two different off-pump surgical methods were used to perform cannulation in sheep
      pulmonary artery to replace part of sheep pulmonary artery with pulmonary valved
      conduit which will work together with sheep pulmonary artery and valves. During
      the experiments, animal survival, complication rates, operating time and blood
      loss were recorded to compare the results between groups and to establish a
      surgical method with minimal invasion, simplicity, safety, and high success
      rates. RESULTS: In group 1, a total of 15 cases of surgeries were performed, in
      which two sheep died; the operative mortality was 13.3% (2/15). In group 2, a
      total of 15 cases of surgeries were performed, and the surgical mortality rate
      was 0 (0/15). The operation time and blood loss in group 2 was significantly
      better than that in group 1. The postoperative echocardiograms showed that, after
      the surgeries by these two methods, the blood flows were normal, and the valves
      can open and close freely. Autopsy after 6 months showed that the inner wall and
      the valves of pulmonary valved conduit were smooth with no thrombus formation.
      CONCLUSION: These two off-pump methods are feasible and safe with fewer traumas;
      but the second method is better and particularly suitable for the establishment
      of a juvenile animal model.

PMID- 24286423
TI  - Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during
      ischemic postconditioning by crosstalk with the RISK signaling pathway.
AB  - BACKGROUND: Ischemic postconditioning (IPost), able to significantly attenuate
      myocardial ischemia reperfusion injury, is dependent on RISK signaling. Studies
      have shown that Notch signaling repairs damaged myocardium, and this study aimed
      to investigate the effect of Notch signaling in myocardial IPost. METHODS: We
      used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R)
      model in vitro. which were randomly divided into control, H/R, IPost, Hepatocyte
      growth factor (HGF)+IPost and DAPT+IPost, N1ICD+IPost, miRNA+IPost, and Mock
      treatment groups. The myocardial cell viability was assessed by MTT, the cell
      apoptosis was detected using Annexin V/PI double staining and flow cytometry
      analyses. The expression of N1ICD, Hes1, PTEN Phospho-Akt/Akt, Phospho-GSK
      3beta/GSK-3beta were detected by Western blotting. Finally, we assessed the
      changes in psim using the potential-sensitive dye JC-1 and measured using flow
      cytometry analyses. RESULTS: The Notch1 signaling is activated by HGF and ectopic
      expression of N1ICD during myocardial IPost, which increased myocardial cell
      viability, prevented cardiomyocyte apoptosis, and reduced loss of the
      mitochondrial membrane potential. However, myocardial ischemia reperfusion injury
      was increased in IPost when Notch1 signaling was inhibited using DAPT or with
      knockdown by Notch1-miRNA. Western blotting found that PTEN was down-regulated by
      Hes1 when Notch1 was activated, which consequently promoted Akt and GSK-3beta
      phosphorylation. CONCLUSIONS: Notch1 crosstalk with RISK signaling may be
      dependent on PTEN, which plays a cardioprotective role during IPost. This
      mechanism could provide a promising therapeutic target for the treatment of
      ischemic heart disease.

PMID- 24286424
TI  - Demethylating agent decitabine induces autologous cancer testis antigen specific
      cytotoxic T lymphocytes in vivo.
AB  - BACKGROUND: Cancer testis antigens (CTAs) are a novel group of tumor associated
      antigens. Demethylating agent decitabine was reported to be able to up-regulate
      CTAs through its hypomethylation mechanism, thus enhance the immunogenicity of
      leukemia cells. However, few researches have ever focused on the questions that
      whether this immunostimulatory effect of decitabine could induce autologous CTA
      specific cytotoxic T lymphocytes (CTLs) in vivo, and if so, whether this effect
      contributes to disease control. In this study, we aimed to show that decitabine
      could induce specific autologous CTLs against some mouse CTAs in leukemia cells
      in vitro and in vivo. METHODS: Several mouse CTAs were screened by RT-PCR. CTL
      specific to one of the CTAs named P1A was detected and sorted by P1A specific
      dimer by flow cytometry. The activity of specific CTLs was measured by real time
      RT-PCR. RESULTS: We firstly screened expression of some CTAs in mouse leukemia
      cells before and after decitabine treatment and found that decitabine treatment
      did up-regulate expression of many CTAs. Then we measured the CTLs' activity
      specific to a mouse CTA P1A in vivo and showed that this activity increased after
      decitabine treatment. Finally, we sorted these in vivo induced P1A specific CTLs
      by flow cytometry and demonstrated their cytotoxicity against decitabine treated
      leukemia cells. CONCLUSIONS: Our study showed the autologous immune response
      induced by decitabine in vivo. And more importantly, we firstly proved that this
      response may contribute to disease control. We believe that this
      immunostimulatory effect is another anti-cancer mechanism of decitabine, and this
      special effect would inspire new applications of decitabine in the field of
      leukemia treatment in the future.

PMID- 24286425
TI  - An experimental study of using Chai Lai Prescription to treat in vitro rabbit
      models of reflux esophagitis.
AB  - BACKGROUND: Chai Lai Prescription is a Chinese herbal compound which is used to
      sooth the liver, strengthen the spleen and harmonize the stomach for descending
      adverse Qi. We initiated the study to investigate its mechanism of treating in
      vitro rabbit reflux esophagitis models. METHODS: Adult male Japanese white
      rabbits, weighing 1.8-2.2 kg, were divided into five groups of three each, which
      were: normal control group (Krebs buffer, pH7.4), esophagitis model group (Krebs
      buffer, pH5.8), esophagitis model proup+low-dose Chinese herbal medicine
      protection group (0.6 mg * ml(-1)* kg(-1)), esophagitis model group+moderate-dose
      Chinese herbal medicine protection group (6 mg * ml(-1)* kg(-1)), esophagitis
      model group+high-dose Chinese herbal medicine protection group (60 mg * ml(
      1)*kg(-1)). The RT-PCR method was used to test the influence of Chai Lai
      Prescription on IL-1 and IL-6 in in vitro rabbit models of esophagitis. We
      treated the in vitro models with different doses of Chinese herbal medicine.
      RESULTS: Esophageal mucosa were filled with various liquids. IL-6 and IL-1beta
      mRNA expression was increased in rabbit esophageal mucosa stimulated with acid.
      Chinese herbal medicine significantly reduced the levels of IL-6 and IL-1beta
      mRNA expression in the in vitro cultured rabbit esophageal mucosa. Using Chinese
      herbal medicine to treat in vitro models of RE, we found that the IL-6 and IL
      1beta mRNA expression levels went down, near to or lower than the normal control
      levels, compared with the group treated with acidified buffer solution.
      CONCLUSIONS: Chai Lai Prescription lowered the IL-1beta and IL-6 cytokine mRNA
      levels and protected the esophageal mucosa in the in vitro models of reflux
      esophagitis, suggesting that the traditional Chinese herbal compound may be able
      to treat reflux esophagitis by inhibiting the its inflammatory mediators.

PMID- 24286426
TI  - C509T and T869C polymorphisms of transforming growth factor beta1 and the risk of
      IgA nephropathy: a meta-analysis.
AB  - BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease.
      Transforming growth factor beta1 (TGFbeta1) plays an important role in
      pathogenesis of IgAN. Associations between the polymorphisms of TGFbeta1 gene and
      the risk of IgAN remained inconsistent. A meta-analysis was conducted to
      investigate the association between polymorphisms in the TGFbeta1 gene and IgAN
      susceptibility. METHODS: Databases including Pubmed, EMBASE, ISI, et al. were
      searched to find relevant studies. Odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to evaluate the strength of associations. RESULTS: Ten
      studies involving 1770 cases and 1953 controls were included. Significant
      association between C509T polymorphism and IgAN risk was observed (OR 1.42, 95%
      CI 1.12-1.81, P = 0.0004; I(2) = 0%) in Caucasians by the overdominant model (CT
      vs. CC + TT), but no significant association was found (P = 0.200) in Asians by
      the dominant model (CC + CT vs. TT). Significant association between T869C
      polymorphism and IgAN susceptibility was found (OR 1.21, 95% CI 1.02-1.44, P =
      0.030) in overall populations by the dominant model (TT + TC vs. CC). Subgroup
      analysis found T allele of T869C polymorphism was associated with IgAN
      susceptibility in Caucasians (P = 0.030), but not in Asians (P = 0.290).
      CONCLUSION: Both heterozygotes of C509T polymorphism and T allele of T869C
      polymorphism in TGFbeta1 were associated with the risk of IgAN in Caucasians, but
      not in Asians.

PMID- 24286427
TI  - Antiviral therapy for "difficult-to-treat" hepatitis C virus-infected patients.
AB  - OBJECTIVE: To review the updated research on direct antiviral agents (DAAs)
      including regimens for hepatitis C virus (HCV), and focus on "difficult-to-treat"
      HCV-infected patients. DATA SOURCES: The literature concerning DAAs and hepatitis
      C cited in this review was collected from PubMed and Google Scholar databases
      published in English up to July 2013. STUDY SELECTION: Data from published
      articles regarding HCV and DAAs in clinical trials and in clinical use were
      identified and reviewed. RESULTS: It was recognized that some "difficult-to
      treat" patients would still exist, even though stronger treatments using such as
      DAAs, including telaprevir and boceprevir, which lead to higher sustained
      virological response rates, are available. Such patients include those with
      advanced fibrosis/cirrhosis, elderly persons, children, HCV-human
      immunodeficiency virus co-infected patients, HCV-infected recipients, and so on.
      CONCLUSIONS: Certain "difficult-to-treat" patients would still exist, even though
      stronger treatment is available. Although evidence from clinical trials is still
      lacking, interferon-sparing regimens could have stronger effects for eradicating
      HCV in such cases.

PMID- 24286428
TI  - Ex vivo expansion of regulatory T cells for clinical applications against graft
      versus-host disease in allogeneic hematopoietic stem cell transplantation.
AB  - OBJECTIVE: To review the characteristics of regulatory T cells (Tregs) and ex
      vivo expansion of Tregs for treatment of graft-versus-host disease (GVHD). DATA
      SOURCES: The data used in this review were retrieved from PubMed (1970-2013). The
      terms "ex vivo expansion", "regulatory T cell", and "graft-versus-host disease"
      were used for literature search. STUDY SELECTION: The publications about the
      characteristics of Tregs, ex vivo expansion of Tregs and clinical applications of
      Tregs against GVHD were identified, retrieved and reviewed. RESULTS: Tregs can be
      classified as natural Tregs (nTregs) and induced Tregs (iTregs). Both subsets
      share most Treg features. Given their immunosuppressive property, Tregs have been
      tested for their capability of preventing GVHD. The bottleneck of Treg therapy is
      the limited numbers of naturally existing Tregs. To solve this problem, ex vivo
      expansion of nTregs or iTregs has been executed. The initial data indicate Treg
      therapy is effective in reducing GVHD without compromising graft-versus-leukemia
      (GVL). CONCLUSION: Ex vivo expansion of Tregs is a reliable way to prepare
      sufficient number of Tregs for management of GVHD.

PMID- 24286429
TI  - Tbx1 regulates the development of zebrafish neural crest cells by retinoic acid
      signaling.

PMID- 24286430
TI  - Effects of pre-pregnancy body mass index on pregnancy outcomes.

PMID- 24286431
TI  - Postmenopausal endometriosis: a retrospective analysis of 69 patients during a 20
      year period.

PMID- 24286432
TI  - Hemorrhagic shock caused by rupture of cystic artery pseudoaneurysm secondary to
      calculous cholecystitis.

PMID- 24286433
TI  - Salvage radical prostatectomy for radiorecurrent prostate cancer: the Chinese
      experience.

PMID- 24286434
TI  - Current status of cord blood transplantation in China.

PMID- 24286435
TI  - A rare case of extraosseous Ewing sarcoma primarily arising in the ovary.

PMID- 24286436
TI  - Did splenectomy influence relapse of chronic myelogenous leukemia after
      allogeneic hematopoietic stem cell transplantation?

PMID- 24286437
TI  - Huge trichilemmal carcinoma of the scalp.

PMID- 24286438
TI  - Lower bile duct stenosis caused by xanthogranulomatous cholangitis complicated
      with jaundice.

PMID- 24286440
TI  - Predator effects on a detritus-based food web are primarily mediated by non
      trophic interactions.
AB  - Predator effects on ecosystems can extend far beyond their prey and are often not
      solely lethally transmitted. Change in prey traits in response to predation risk
      can have important repercussions on community assembly and key ecosystem
      processes (i.e. trait-mediated indirect effects). In addition, some predators
      themselves alter habitat structure or nutrient cycling through ecological
      engineering effects. Tracking these non-trophic pathways is thus an important,
      yet challenging task to gain a better grasp of the functional role of predators.
      Multiple lines of evidence suggest that, in detritus-based food webs, non-trophic
      interactions may prevail over purely trophic interactions in determining predator
      effects on plant litter decomposition. This hypothesis was tested in a headwater
      stream by modulating the density of a flatworm predator (Polycelis felina) in
      enclosures containing oak (Quercus robur) leaf litter exposed to natural
      colonization by small invertebrates and microbial decomposers. Causal path
      modelling was used to infer how predator effects propagated through the food web.
      Flatworms accelerated litter decomposition through positive effects on microbial
      decomposers. The biomass of prey and non-prey invertebrates was not negatively
      affected by flatworms, suggesting that net predator effect on litter
      decomposition was primarily determined by non-trophic interactions. Flatworms
      enhanced the deposition and retention of fine sediments on leaf surface, thereby
      improving leaf colonization by invertebrates - most of which having strong
      affinities with interstitial habitats. This predator-induced improvement of
      habitat availability was attributed to the sticky nature of the mucus that
      flatworms secrete in copious amount while foraging. Results of path analyses
      further indicated that this bottom-up ecological engineering effect was as
      powerful as the top-down effect on invertebrate prey. Our findings suggest that
      predators have the potential to affect substantially carbon flow and nutrient
      cycling in detritus-based ecosystems and that this impact cannot be fully
      appreciated without considering non-trophic effects. 

PMID- 24286439
TI  - The rulB gene of plasmid pWW0 is a hotspot for the site-specific insertion of
      integron-like elements found in the chromosomes of environmental Pseudomonas
      fluorescens group bacteria.
AB  - The rulAB operon of Pseudomonas spp. confers fitness traits on the host and has
      been suggested to be a hotspot for insertion of mobile elements that carry
      avirulence genes. Here, for the first time, we show that rulB on plasmid pWW0 is
      a hotspot for the active site-specific integration of related integron-like
      elements (ILEs) found in six environmental pseudomonads (strains FH1-FH6).
      Integration into rulB on pWW0 occurred at position 6488 generating a 3 bp direct
      repeat. ILEs from FH1 and FH5 were 9403 bp in length and contained eight open
      reading frames (ORFs), while the ILE from FH4 was 16 233 bp in length and
      contained 16 ORFs. In all three ILEs, the first 5.1 kb (containing ORFs 1-4) were
      structurally conserved and contained three predicted site-specific
      recombinases/integrases and a tetR homologue. Downstream of these resided ORFs of
      the 'variable side' with structural and sequence similarity to those encoding
      survival traits on the fitness enhancing plasmid pGRT1 (ILE(FH1) and ILE(FH5))
      and the NR-II virulence region of genomic island PAGI-5 (ILE(FH4)). Collectively,
      these ILEs share features with the previously described type III protein
      secretion system effector ILEs and are considered important to host survival and
      transfer of fitness enhancing and (a)virulence genes between bacteria.

PMID- 24286441
TI  - Low-molecular-weight heparin (LMWH)-loaded large porous PEG-PLGA particles for
      the treatment of asthma.
AB  - BACKGROUND: Heparin-like compounds interrupt leukocyte adhesion and migration,
      and prevent release of chemical mediators during the process of inflammation.
      However, little is known whether the anti-inflammatory property of smaller
      heparin fragments, low-molecular-weight heparin (LMWH), plays any role in the
      process of airway inflammation. In this study, we sought to evaluate the efficacy
      of LMWH-loaded large porous polyethylene glycol-poly(D,L-lactide-co-glycolide)
      (PEG-PLGA) particulate formulations in alleviating the cellular and biochemical
      changes associated with asthma. METHODS: To study the pharmacological efficacy of
      LMWH for the treatment of asthma, we have used a previously optimized polymeric
      formulation of LMWH. The anti-asthmatic efficacy of the optimized formulation was
      studied in an ovalbumin-sensitized rat model of asthma. The influence of the
      formulation on asthmatic lungs was assessed by measuring the total protein
      content and number of inflammatory cells in the bronchoalveolar lavage fluid
      (BALF). Lungs were also examined for morphological and structural changes that
      may occur in asthmatic lungs. RESULTS: Compared with healthy animals, asthmatic
      animals showed a seven- and threefold increase in the protein content and number
      of inflammatory cells in BALF, respectively. However, intratracheal LMWH
      particles reduced the protein content by 2.5-fold and the number of inflammatory
      cells by 1.8-fold-comparable to those of sham animals. Similarly, LMWH particles
      reduced the lactate dehydrogenase levels by 2.8- and threefold in BALF and
      plasma, respectively. The airway wall thickness also decreased from 47.37+/-6.02
      MUm to 21.35+/-3.60 MUm upon treatment with PEG-PLGA particles of LMWH. Goblet
      cell hyperplasia was also reduced in asthmatic rats treated with LMWH particles.
      CONCLUSION: PLGA particles of LMWH were efficacious in improving cellular and
      histological changes associated with asthma, and thus this polymeric formulation
      has the potential for further development into a clinically viable anti-asthma
      therapy.

PMID- 24286442
TI  - Amyloid arthropathy associated with multiple myeloma: polyarthritis without
      synovial infiltration of CD20+ or CD38+ cells.
AB  - OBJECTIVES: To describe histological, immunohistochemical and ultrastructural
      features of synovial biopsies of amyloid arthropathy associated with multiple
      myeloma (MM). METHODS: Synovial biopsies from affected joints of two patients
      with MM and amyloid arthropathy were examined with light and electron microscopy,
      and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and
      vWF. Results were compared to values from osteoarthritis (OA, n = 26), rheumatoid
      arthritis (RA, n = 24) and normal (n = 15) synovial membranes. RESULTS: There was
      no or only mild lining hyperplasia. Vascular density was not elevated, and there
      were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score
      classified one specimen as "low-grade" and one as "high-grade" synovitis. CD68+
      and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+
      and CD38+ cells were absent from both synovial membrane and synovial fluid
      sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial
      macrophages. In hierarchical clustering the two amyloid arthropathy specimens
      were more closely related to OA than to RA or normal synovium. CONCLUSIONS: This
      first detailed immunohistological analysis of MM-associated amyloid arthropathy
      suggests that it is a chronic synovitis that evolves despite the loss of humoral
      immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial
      macrophages likely triggers and perpetuates local disease.

PMID- 24286443
TI  - Dietary flavanol intervention lowers the levels of endothelial microparticles in
      coronary artery disease patients.
AB  - Current evidence suggests that regenerative v. degenerative endothelial responses
      can be integrated in a clinical endothelial phenotype, reflecting the net result
      between damage from risk factors and endogenous repair capacity. We have
      previously shown that a cocoa flavanol (CF) intervention can improve endothelial
      function and increase the regenerative capacity of the endothelium by mobilising
      circulating angiogenic cells in patients with coronary artery disease (CAD). The
      aim of the present study was to investigate whether CF can lower the levels of
      circulating endothelial microparticles (EMP), markers of endothelial integrity,
      along with improvements in endothelial function. The levels of EMP in the frozen
      plasma samples of CAD patients were measured along with endothelial function
      (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and
      these data were compared with those of young (n 12) and age-matched (n 12)
      healthy control subjects. The CAD patients exhibited significantly increased
      levels of EMP along with impaired FMD when compared with the healthy control
      subjects. The levels of CD144+ and CD31+/41- EMP were inversely correlated with
      FMD (r -0.67, P=0.01 and r -0.59, P=0.01, respectively). In these CAD patients,
      the levels of EMP were measured after they had consumed a drink containing 375 mg
      of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient
      matched low-CF control, LoFl) twice daily over a 30-d period in a randomised,
      double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41-
      and CD144+ EMP decreased (-25 and -23%, respectively), but not after LoFl. Our
      data show that flavanols lower the levels of EMP along with higher endothelial
      function, lending evidence to the novel concept that flavanols may improve
      endothelial integrity.

PMID- 24286444
TI  - Patient education, disease activity and physical function: can we be more
      targeted? A cross sectional study among people with rheumatoid arthritis,
      psoriatic arthritis and hand osteoarthritis.
AB  - INTRODUCTION: In order to target educational needs of patients more effectively,
      an Austrian-German educational needs assessment tool (OENAT) was developed, the
      educational needs of patients with rheumatoid arthritis (RA), psoriatic arthritis
      (PsA) and hand osteoarthritis (HOA) were described and the relationships between
      educational needs, gender, disease activity and function were explored. METHODS:
      The English ENAT was adapted into Austrian-German using Beaton's cross-cultural
      adaptation process. Internal construct validity was assessed by Rasch analysis.
      Educational needs across diagnostic groups and subgroups of patients were
      summarized descriptively and their relationship with disease activity and
      physical functioning explored. RESULTS: The sample comprised 130 RA, 125 PsA and
      48 HOA patients. Their mean ages +/- SD were 56 +/- 14, 51 +/- 11 and 64 +/- 7
      years for RA, PsA and HOA; disease duration was 11 +/- 9, 11 +/- 11 and 14 +/- 9
      years, respectively. More than 70% in each patient group expressed interest in
      receiving education about their disease. CONCLUSIONS: This study showed that
      educational needs vary with personal characteristics. Patient education may be
      more targeted and effective, if gender, age, educational background and disease
      duration are taken into account. Correlations with disease activity and function
      suggest that the OENAT could enable identification of 'intervention points',
      which can be ideal opportunities for effective patient education.

PMID- 24286445
TI  - Tubeless simultaneous bilateral percutaneous nephrolithotomy: safety, feasibility
      and efficacy in an Indian setting.
AB  - OBJECTIVES: To study the safety, feasibility and efficacy of tubeless
      simultaneous bilateral percutaneous nephrolithotomy. METHODS: We retrospectively
      studied 85 patients who underwent tubeless simultaneous bilateral percutaneous
      nephrolithotomy in the Department of Urology, Kasturba Medical College, Manipal,
      Karnataka, India, from July 2006 to June 2013. The demographic profile and
      outcomes were compared with the other existing series reported in the literature.
      RESULTS: A total of 65 male and 20 female patients with a mean age of 45.7 +/-
      11.6 years underwent tubeless simultaneous bilateral percutaneous
      nephrolithotomy. The mean stone burden was 299 mm(2), with 12 staghorn calculi.
      Mean operative time was 87.6 +/- 35.5 min. A total of 95% of stones were cleared
      with single access tracts. The success rate of tubeless simultaneous bilateral
      percutaneous nephrolithotomy (stone clearance) was 95.2%. Mean hemoglobin drop
      was 1.1 +/- 0.9 gm% per patient, with 10.5% of patients requiring blood
      transfusion. Mean hospital stay was 69.6 +/- 28.4 h. Complications included
      urosepsis (Clavien grade 4), acute kidney injury requiring hemodialysis (grade
      3), pneumonia (grade = 2) and hydrothorax requiring intercostal drainage tube
      insertion (grade 3). On follow up, 4.7% of the renal units required ancillary
      procedures. CONCLUSIONS: Our findings confirm that tubeless simultaneous
      bilateral percutaneous nephrolithotomy is a safe and effective modality of
      treatment. It allows obviating a second anesthetic exposure, thus reducing
      analgesic requirement, hospitalization time and costs. This translates into a
      significant socioeconomic impact on the outlook of Indian patients presenting
      with bilateral renal stone disease.

PMID- 24286447
TI  - Rituximab in severe, treatment-refractory interstitial lung disease.
AB  - BACKGROUND AND OBJECTIVE: In patients with severe interstitial lung disease (ILD)
      progressing despite conventional immunosuppression, rituximab, a B-lymphocyte
      depleting monoclonal antibody, may offer an effective rescue therapy. METHODS:
      Retrospective assessment of 50 patients with severe, progressive ILD (of varying
      aetiologies, excluding idiopathic pulmonary fibrosis (IPF)) treated with
      rituximab between 2010 and 2012. Change in pulmonary function tests compared with
      pre-rituximab levels was assessed at 6-12 months post-treatment. RESULTS: ILD was
      associated with connective tissue disease in 33 patients, hypersensitivity
      pneumonitis in 6 patients and miscellaneous conditions in 11 patients. At the
      time of rituximab administration, patients had severe physiologic impairment with
      a median forced vital capacity (FVC) of 44.0% (24.0-99.0%) and diffusing capacity
      of carbon monoxide (DLCO ) of 24.5% (11.4-67.0%). In contrast with a median
      decline in FVC of 14.3% and DLCO of 18.8% in the 6-12 months prior to rituximab,
      analysis of paired pulmonary function data revealed a median improvement in FVC
      of 6.7% (P < 0.01) and stability of DLCO (0% change; P < 0.01) in the 6-12 months
      following rituximab treatment. Two patients developed serious infections
      (pneumonia) requiring hospitalization following rituximab, and 10 patients died
      from progression of underlying ILD, a median of 5.1 (1.2-24.5) months after
      treatment. CONCLUSIONS: In patients with severe, progressive non-IPF ILD
      unresponsive to conventional immunosuppression, rituximab may offer an effective
      therapeutic intervention. Future prospective, controlled trials are warranted to
      validate these findings, and to assess safety outcomes.

PMID- 24286446
TI  - Immediate-type hypersensitivity drug reactions.
AB  - Hypersensitivity reactions including anaphylaxis have been reported for nearly
      all classes of therapeutic reagents and these reactions can occur within minutes
      to hours of exposure. These reactions are unpredictable, not directly related to
      dose or the pharmacological action of the drug and have a relatively high
      mortality risk. This review will focus on the clinical presentation, immune
      mechanisms, diagnosis and prevention of the most serious form of immediate onset
      drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced
      anaphylaxis deaths appears to be increasing and our understanding of the multiple
      and complex reasons for the unpredictable nature of anaphylaxis to drugs is also
      expanding. This review highlights the importance of enhancing our understanding
      of the biology of the patient (i.e. immune response, genetics) as well as the
      pharmacology and chemistry of the drug when investigating, diagnosing and
      treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to
      substantial patient risk and cost. Although oral provocation is often considered
      the gold standard of diagnosis, it can pose a potential risk to the patient.
      There is an urgent need to improve and standardize diagnostic testing and
      desensitization protocols as other diagnostic tests currently available for
      assessment of immediate drug allergy are not highly predictive. 

PMID- 24286448
TI  - Touching moments: phenomenological sociology and the haptic dimension in the
      lived experience of motor neurone disease.
AB  - Currently, there is a relative research lacuna in phenomenological research into
      the lived experience of motor neurone disease. Based on a sociological research
      project in the UK, involving 42 participants diagnosed with MND, this article
      explores the potential of a phenomenological sociology for analysing experiences
      of this drastically life-limiting neurological disorder. Calls have been made for
      sociological researchers to analyse more fully and deeply the sensory dimension
      of the lived body, and this article also contributes to this newly developing
      body of literature. While the social sciences have been accused of a high degree
      of ocularcentrism, here we take forward the literature by specifically focusing
      upon the haptic dimension, given that touch - and particularly the loss of key
      elements of the haptic dimension- emerged as salient in MND patients' accounts.
      To illustrate the potential of our phenomenologically inspired theoretical
      perspective, we consider two specific haptic themes: (i) being out of touch: the
      loss of certain forms of touch within MND and (ii) unwelcome touch by medical
      staff. 

PMID- 24286449
TI  - Transglutaminase activity as a possible therapeutical target in neurodegenerative
      diseases.
AB  - Transglutaminases are ubiquitous enzymes which catalyze post-translational
      modifications of proteins. The main activity of these enzymes is the cross
      linking of glutaminyl residues of a protein/peptide substrate to lysyl residues
      of a protein/peptide co-substrate. In addition to lysyl residues, other second
      nucleophilic co-substrates may include monoamines or polyamines (to form mono- or
      bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In
      absence of co-substrates, the nucleophile may be water, resulting in the net
      deamidation of the glutaminyl residue. Transglutaminase activity has been
      suggested to be involved in molecular mechanisms responsible for both
      physiological or pathological processes. For example, neurodegenerative diseases,
      such as Alzheimer's Disease, Parkinson's Disease, supranuclear palsy,
      Huntington's Disease and other polyglutamine diseases, are characterized in part
      by aberrant cerebral transglutaminase activity and by increased cross-linked
      proteins in affected brains. This review focuses on the possible molecular
      mechanisms responsible for such diseases and on the possible therapeutic effects
      of selective transglutaminase inhibitors for patients with diseases characterized
      by aberrant transglutaminase activity. The article presents some promising
      patents on the transglutaminase activity. 

PMID- 24286450
TI  - Patents on brain permeable nanoparticles.
AB  - The blood-brain barrier (BBB) presents a combination of physical and
      electrostatic barriers. It is a highly complex structure that tightly regulates
      the movement of molecules from the blood to brain, protecting it from injuries
      and diseases. However, the BBB also significantly precludes the delivery of drugs
      to the brain, thus, preventing the therapy of a number of neurological disorders
      like brain cancer, epilepsy, Alzheimer's disease, schizophrenia etc. Numerous
      drug delivery strategies have been developed to circumvent this barrier. Out of
      those, one popular approach is the use of nanoparticles. Nanoparticles form
      solid, colloidal drug delivery system that consists of macromolecular materials
      in which the active principle is dissolved, entrapped or encapsulated or onto
      which the active principle is adsorbed or attached. Brain targeted polymeric
      nanoparticles have been found to increase the therapeutic efficacy and reduce the
      toxicity for a large number of drugs. By coating the nanoparticles with
      surfactants, higher concentrations of the drugs can be delivered. The article
      presents various approaches used in design and delivery of nanoparticles to
      brain. It also reviews various patents that describe the use of nanoparticles to
      deliver various neurotherapeutics to brain. 

PMID- 24286451
TI  - Attainable region analysis for continuous production of second generation
      bioethanol.
AB  - BACKGROUND: Despite its semi-commercial status, ethanol production from
      lignocellulosics presents many complexities not yet fully solved. Since the
      pretreatment stage has been recognized as a complex and yield-determining step,
      it has been extensively studied. However, economic success of the production
      process also requires optimization of the biochemical conversion stage. This work
      addresses the search of bioreactor configurations with improved residence times
      for continuous enzymatic saccharification and fermentation operations. Instead of
      analyzing each possible configuration through simulation, we apply graphical
      methods to optimize the residence time of reactor networks composed of steady
      state reactors. Although this can be easily made for processes described by a
      single kinetic expression, reactions under analysis do not exhibit this feature.
      Hence, the attainable region method, able to handle multiple species and its
      reactions, was applied for continuous reactors. Additionally, the effects of the
      sugars contained in the pretreatment liquor over the enzymatic hydrolysis and
      simultaneous saccharification and fermentation (SSF) were assessed. RESULTS: We
      obtained candidate attainable regions for separate enzymatic hydrolysis and
      fermentation (SHF) and SSF operations, both fed with pretreated corn stover.
      Results show that, despite the complexity of the reaction networks and underlying
      kinetics, the reactor networks that minimize the residence time can be
      constructed by using plug flow reactors and continuous stirred tank reactors.
      Regarding the effect of soluble solids in the feed stream to the reactor network,
      for SHF higher glucose concentration and yield are achieved for enzymatic
      hydrolysis with washed solids. Similarly, for SSF, higher yields and bioethanol
      titers are obtained using this substrate. CONCLUSIONS: In this work, we
      demonstrated the capabilities of the attainable region analysis as a tool to
      assess the optimal reactor network with minimum residence time applied to the SHF
      and SSF operations for lignocellulosic ethanol production. The methodology can be
      readily modified to evaluate other kinetic models of different substrates,
      enzymes and microorganisms when available. From the obtained results, the most
      suitable reactor configuration considering residence time and rheological aspects
      is a continuous stirred tank reactor followed by a plug flow reactor (both in SSF
      mode) using washed solids as substrate.

PMID- 24286452
TI  - Editorial.

PMID- 24286454
TI  - The paradox of marine heterotrophic nitrogen fixation: abundances of
      heterotrophic diazotrophs do not account for nitrogen fixation rates in the
      Eastern Tropical South Pacific.
AB  - Results of recent modelling efforts imply denitrification-influenced waters, such
      as those in the Eastern Tropical South Pacific (ETSP), may support high rates of
      biological nitrogen fixation (BNF), yet little is known about the N2 -fixing
      microbial community in this region. Our characterization of the ETSP diazotrophic
      community along a gradient from upwelling-influenced to oligotrophic waters did
      not detect cyanobacterial diazotrophs commonly found in other open ocean regions.
      Most of the nifH genes amplified by polymerase chain reaction (PCR) from DNA and
      RNA samples clustered with gamma-proteobacterial nifH sequences, although a novel
      Trichodesmium phylotype was also recovered. Three quantitative PCR assays were
      developed to target gamma-proteobacterial phylotypes, but all were found to be
      present at low abundances. An analysis of the expected BNF rates based on
      abundances and plausible cell-specific N2 fixation rates indicates that these
      gamma-proteobacteria are unlikely to be responsible for previously reported BNF
      rates from corresponding samples. Therefore, the organisms responsible for the
      measured BNF rates remain poorly understood. Furthermore, there is little direct
      evidence, at this time, to support the hypothesis that heterotrophic N2 fixation
      contributes significantly to oceanic BNF rates based on our analysis of
      heterotrophic cell-specific N2 fixation rates required to explain BNF rates
      reported in previously published studies.

PMID- 24286455
TI  - Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity.
AB  - INTRODUCTION: HLA-B27 genotyping is commonly used to support a diagnosis of
      ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may
      adversely affect longevity. The objectives of this study were to determine, for
      the first time, the prevalence of HLA-B27 in the New Zealand population, and to
      test whether HLA-B27 prevalence declines with age. METHODS: 117 Caucasian
      controls, 111 New Zealand Maori controls, and 176 AS patients were directly
      genotyped for HLA-B27 using PCR-SSP. These participants and a further 1103
      Caucasian controls were genotyped for the HLA-B27 tagging single nucleotide
      polymorphisms (SNPs) rs4349859 and rs116488202. All AS patients testing positive
      for HLA-B27 of New Zealand Maori ancestry underwent high resolution typing to
      determine sub-allele status. RESULTS: HLA-B27 prevalence was 9.2% in New Zealand
      Caucasian controls and 6.5% in Maori controls. No decline in HLA-B27 prevalence
      with age was detected in Caucasian controls (p = 0.92). Concordance between HLA
      B27 and SNP genotypes was 98.7-99.3% in Caucasians and 76.9-86% in Maori. Of the
      14 AS patients of Maori ancestry, 1 was negative for HLA-B27, 10 were positive
      for HLAB*2705, and 3 positive for HLAB*2704. All cases of genotype discordance
      were explained by the presence of HLAB*2704. CONCLUSIONS: HLA-B27 prevalence in
      New Zealand Caucasians is consistent with that of Northern European populations
      and did not decline with increasing age. In Maori with AS who were HLA-B27
      positive, 76.9% were positive for HLA-B*2705, suggesting that genetic
      susceptibility to AS in Maori is primarily due to admixture with Caucasians.

PMID- 24286456
TI  - Safety and efficacy of an oral CCR3 antagonist in patients with asthma and
      eosinophilic bronchitis: a randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: Several chemokines, notably eotaxin, mediate the recruitment of
      eosinophils into tissues via the CCR3 receptor. OBJECTIVE: In this study, we
      investigated the role of CCR3 agonists in asthma by observing the effect of a
      small molecule antagonist of the CCR3 receptor (GW766994) on sputum eosinophil
      counts in patients with eosinophilic asthma. METHODS: Clinical and physiological
      outcomes, the chemotactic activity of sputum supernatant for eosinophils and the
      presence of eosinophil progenitors in sputum and blood samples were also studied.
      RESULTS: In a double-blind parallel group study, 60 patients with asthma were
      randomized to 300 mg of GW766994 twice daily or matching placebo for 10 days
      followed by prednisone 30 mg for 5 days. Of these patients, 53 had a sputum
      eosinophil count > 4.9% at baseline. Despite plasma concentrations of drug
      consistent with > 90% receptor occupancy during the dosing period, the CCR3
      antagonist did not significantly reduce eosinophils or eosinophil progenitor
      cells (CD34(+) 45(+) IL-5Ralpha(+)) in sputum or in blood. The ex vivo
      chemotactic effect of sputum supernatants on eosinophils was attenuated by
      GW766944 compared to placebo. There was no improvement in FEV1 ; however, there
      was a modest but statistically significant improvement in PC20 methacholine (0.66
      doubling dose) and ACQ scores, (0.43). Whilst the improvement in PC20 is
      statistically significant, it is not of clinical significance. CONCLUSIONS AND
      CLINICAL RELEVANCE: In conclusion, this study calls into question the role of
      CCR3 in airway eosinophilia in asthma and suggests that other cellular mechanisms
      mediated by the CCR3 receptor may contribute to airway hyperresponsiveness.

PMID- 24286457
TI  - Identifying population differences in genes that affect body mass index.
AB  - Genomic regions of interest can be narrowed by studying populations that have
      patterns of low linkage disequilibrium. A recent study of body mass index in
      African Americans demonstrated this point and, through cross-population analyses,
      revealed additional genomic associations. This comparative analysis showed how
      rare alleles that associate with traits in specific populations can be detected
      in cohorts where the same alleles are not rare, and highlights how population
      diversity can aid genetic analyses. 

PMID- 24286458
TI  - Cholesterol accumulation caused by low density lipoprotein receptor deficiency or
      a cholesterol-rich diet results in ectopic bone formation during experimental
      osteoarthritis.
AB  - INTRODUCTION: Osteoarthritis (OA) is associated with the metabolic syndrome,
      however the underlying mechanisms remain unclear. We investigated whether low
      density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial
      macrophages and affects synovial activation, cartilage destruction and
      enthesophyte/osteophyte formation during experimental OA in mice. METHODS: LDL
      receptor deficient (LDLr-/-) mice and wild type (WT) controls received a
      cholesterol-rich or control diet for 120 days. Experimental OA was induced by
      intra-articular injection of collagenase twelve weeks after start of the diet. OA
      knee joints and synovial wash-outs were analyzed for OA-related changes. Murine
      bone marrow derived macrophages were stimulated with oxidized LDL (oxLDL),
      whereupon growth factor presence and gene expression were analyzed. RESULTS: A
      cholesterol-rich diet increased apolipoprotein B (ApoB) accumulation in synovial
      macrophages. Although increased LDL levels did not enhance thickening of the
      synovial lining, S100A8 expression within macrophages was increased in WT mice
      after receiving a cholesterol-rich diet, reflecting an elevated activation
      status. Both a cholesterol-rich diet and LDLr deficiency had no effect on
      cartilage damage; in contrast, ectopic bone formation was increased within joint
      ligaments (fold increase 6.7 and 6.1, respectively). Moreover, increased
      osteophyte size was found at the margins of the tibial plateau (4.4 fold increase
      after a cholesterol-rich diet and 5.3 fold increase in LDLr-/- mice). Synovial
      wash-outs of LDLr-/- mice and supernatants of macrophages stimulated with oxLDL
      led to increased transforming growth factor-beta (TGF-beta) signaling compared to
      controls. CONCLUSIONS: LDL accumulation within synovial lining cells leads to
      increased activation of synovium and osteophyte formation in experimental OA.
      OxLDL uptake by macrophages activates growth factors of the TGF-superfamily.

PMID- 24286460
TI  - Expansion of the dengue transmission area in Brazil: the role of climate and
      cities.
AB  - OBJECTIVES: To examine the spatial and temporal patterns of the recent expansion
      of dengue transmission area in Brazil (2001-2012) with the aim to identify
      pathways and constraints to dengue diffusion. METHODS: Synthetic indicators were
      calculated to characterise timing (year of first dengue outbreak), permanence
      (number of years with dengue outbreaks) and intensity (outbreak occurrence). The
      indicators were used to map dengue diffusion and compare cities within different
      climatic zones, with varying population densities. RESULTS: Currently, a large
      portion of the country comprises a dengue transmission area, but cities situated
      in the mesothermal zone, in the south, and remote areas, in the north, are
      relatively exempt. Diffusion waves are spread from metropolitan areas towards
      medium and small cities generating outbreaks in their influence region. However,
      long-term permanence of transmission depends on the existence of a favourable
      climate, abundant population and connectivity. CONCLUSIONS: Large and warm cities
      sustain and spread dengue viruses, for which specific dengue control measures
      must be developed. The concentration of outbreaks along climate transition
      fringes indicates a boundary between two transmission regimes and raises
      awareness to the effects of ongoing climatic and socio-economic changes.

PMID- 24286459
TI  - Substandard drugs: a potential crisis for public health.
AB  - Poor-quality medicines present a serious public health problem, particularly in
      emerging economies and developing countries, and may have a significant impact on
      the national clinical and economic burden. Attention has largely focused on the
      increasing availability of deliberately falsified drugs, but substandard
      medicines are also reaching patients because of poor manufacturing and quality
      control practices in the production of genuine drugs (either branded or generic).
      Substandard medicines are widespread and represent a threat to health because
      they can inadvertently lead to healthcare failures, such as antibiotic resistance
      and the spread of disease within a community, as well as death or additional
      illness in individuals. This article reviews the different aspects of substandard
      drug formulation that can occur (for example, pharmacological variability between
      drug batches or between generic and originator drugs, incorrect drug quantity and
      presence of impurities). The possible means of addressing substandard
      manufacturing practices are also discussed. A concerted effort is required on the
      part of governments, drug manufacturers, charities and healthcare providers to
      ensure that only drugs of acceptable quality reach the patient. 

PMID- 24286461
TI  - Faecal calprotectin testing for differentiating amongst inflammatory and non
      inflammatory bowel diseases: systematic review and economic evaluation.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is common, and causes pain, bloating
      and diarrhoea and/or constipation. It is a troublesome condition that reduces the
      quality of life but causes no permanent damage. Inflammatory bowel disease (IBD)
      comprises mainly ulcerative colitis (UC) and Crohn's disease (CD). Both cause
      serious complications and may lead to sections of the bowel having to be removed,
      although this is more common with CD. The presenting symptoms of IBS and IBD can
      be similar. Distinguishing them on clinical signs and symptoms can be difficult.
      Until recently, colonoscopy was often required to rule out IBD. In younger
      people, > 60% of colonoscopies showed no abnormality. Faecal calprotectin (FC) is
      a protein released by the white blood cells, neutrophils, found in inflamed areas
      of the bowel in IBD. Determining the level of FC in stool samples may help
      distinguish IBS from IBD. OBJECTIVE: To review the value of FC for distinguishing
      between IBD and non-IBD. DATA SOURCES: Sources included MEDLINE, EMBASE, The
      Cochrane Library, Web of Science, websites of journals and the European Crohn's
      and Colitis Organisation (conference abstracts 2012 and 2013), and contact with
      experts. REVIEW METHODS: Systematic review and economic modelling. Review Manager
      (RevMan) version 5.2 (The Cochrane Collaboration, The Nordic Cochrane Centre,
      Copenhagen, Denmark) was used for most analysis, with statistical analyses done
      in Stata version 12 (StataCorp LP, College Station, TX, USA). Forest plots and
      receiver operating characteristic curves were produced. Quality Assessment of
      Diagnostic Accuracy Studies was used for quality assessment. Economic modelling
      was done in Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA).
      LIMITATIONS: Studies were often small, most used only one calprotectin cut-off
      level, and nearly all came from secondary care populations. RESULTS: Twenty-eight
      studies provided data for 2 * 2 tables and were included in meta-analyses, with
      seven in the most important comparison in adults (IBS vs. IBD) and eight in the
      key comparison in paediatrics (IBD vs. non-IBD). Most studies used laboratory
      enzyme-linked immunosorbent assay (ELISA) tests. For distinguishing between IBD
      and IBS in adults, these gave pooled sensitivity of 93% and specificity of 94% at
      FC cut-off level of 50 ug/g. Sensitivities at that cut-off ranged from 83% to
      100%, and specificities from 60% to 100%. For distinguishing between IBD and non
      IBD in paediatric populations with ELISA tests, sensitivities ranged from 95% to
      100% at cut-off of 50 ug/g and specificities of 44-93%. Few studies used point-of
      care testing but that seemed as reliable as ELISA, though perhaps less specific.
      The evidence did not provide any grounds for preferring one test over others on
      clinical effectiveness grounds. FC testing in primary care could reduce the need
      for referral and colonoscopies. Any quality-adjusted life-year gains are likely
      to be small because of the low prevalence of IBD and the high sensitivities of
      all of the tests, resulting in few false negatives with IBD. However,
      considerable savings could accrue. Areas of uncertainty include the optimum
      management of people with borderline results (50-150 ug/g), most of whom do not
      have IBD. Repeat testing may be appropriate before referral. CONCLUSIONS: Faecal
      calprotectin can be a highly sensitive way of detecting IBD, although there are
      inevitably trade-offs between sensitivity and specificity, with some false
      positives (IBS with positive calprotectin) if a low calprotectin cut-off is used.
      In most cases, a negative calprotectin rules out IBD, thereby sparing most people
      with IBS from having to have invasive investigations, such as colonoscopy. STUDY
      REGISTRATION: PROSPERO CRD 42012003287. FUNDING: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 24286462
TI  - Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis.
AB  - To date, there is rapidly increasing evidence for host-microbe interaction at
      virtually all levels of complexity, ranging from direct cell-to-cell
      communication to extensive systemic signalling, and involving various organs and
      organ systems, including the central nervous system. As such, the discovery that
      differential microbial composition is associated with alterations in behaviour
      and cognition has significantly contributed to establishing the microbiota-gut
      brain axis as an extension of the well-accepted gut-brain axis concept. Many
      efforts have been focused on delineating a role for this axis in health and
      disease, ranging from stress-related disorders such as depression, anxiety and
      irritable bowel syndrome to neurodevelopmental disorders such as autism. There is
      also a growing appreciation of the role of epigenetic mechanisms in shaping brain
      and behaviour. However, the role of epigenetics in informing host-microbe
      interactions has received little attention to date. This is despite the fact that
      there are many plausible routes of interaction between epigenetic mechanisms and
      the host-microbiota dialogue. From this new perspective we put forward novel, yet
      testable, hypotheses. Firstly, we suggest that gut-microbial products can affect
      chromatin plasticity within their host's brain that in turn leads to changes in
      neuronal transcription and eventually alters host behaviour. Secondly, we argue
      that the microbiota is an important mediator of gene-environment interactions.
      Finally, we reason that the microbiota itself may be viewed as an epigenetic
      entity. In conclusion, the fields of (neuro)epigenetics and microbiology are
      converging at many levels and more interdisciplinary studies are necessary to
      unravel the full range of this interaction. 

PMID- 24286463
TI  - Risk factors for the development of well leg compartment syndrome after sex
      reassignment surgery in patients with gender identity disorder.

PMID- 24286464
TI  - Sexual functioning and vaginal changes after radical vaginal trachelectomy in
      early stage cervical cancer patients: a longitudinal study.
AB  - INTRODUCTION: Radical vaginal trachelectomy (RVT) offers low complication rate,
      good survival, and possibility for future childbearing for young women with early
      stage cervical cancer. However, the literature on quality of life (QOL) and
      sexual functioning in patients undergoing RVT is scarce. AIM: The aims of this
      study were to prospectively assess sexual function after RVT and to compare
      scores of sexual function in patients operated by RVT and radical abdominal
      hysterectomy (RAH) with those of age-matched control women from the general
      population. METHODS: Eighteen patients with early stage cervical cancer operated
      with RVT were prospectively included and assessed preoperatively, and 3, 6, and
      12 months postoperatively using validated questionnaires. RAH patients were
      included consecutively and assessed once at 12 months postsurgery, while an age
      matched control group of 30 healthy women was assessed once. MAIN OUTCOME
      MEASURE: Sexual dysfunction total score as measured by the Female Sexual Function
      Index (FSFI) was the main outcome measure. RESULTS: During the 12 months
      posttreatment, RVT patients tended to have persistent sexual dysfunction as
      measured by FSFI (mean overall score <26.55 at each assessment) and Female Sexual
      Distress Scale (mean overall score > 11). Sexual worry (P < 0.001) and lack of
      sexual desire (P = 0.038) were more frequently reported among patients in both
      treatment groups compared with control women. Sexual activity increased
      significantly during the observation time for the RVT group (P = 0.023) and
      reached that of healthy women. Global Health Status score improved over time for
      the RVT group but never reached that of healthy control women (P = 0.029).
      CONCLUSIONS: Our data suggest that patients treated with RVT for early stage
      cervical cancer experience persistent sexual dysfunction up to one year post
      surgery influencing negatively on their QOL.

PMID- 24286465
TI  - Natural malaria infection reduces starvation resistance of nutritionally stressed
      mosquitoes.
AB  - In disease ecology, there is growing evidence that environmental quality
      interacts with parasite and host to determine host susceptibility to an
      infection. Most studies of malaria parasites have focused on the infection costs
      incurred by the hosts, and few have investigated the costs on mosquito vectors.
      The interplay between the environment, the vector and the parasite has therefore
      mostly been ignored and often relied on unnatural or allopatric Plasmodium/vector
      associations. Here, we investigated the effects of natural avian malaria
      infection on both fecundity and survival of field-caught female Culex pipiens
      mosquitoes, individually maintained in laboratory conditions. We manipulated
      environmental quality by providing mosquitoes with different concentrations of
      glucose-feeding solution prior to submitting them to a starvation challenge. We
      used molecular-based methods to assess mosquitoes' infection status. We found
      that mosquitoes infected with Plasmodium had lower starvation resistance than
      uninfected ones only under low nutritional conditions. The effect of nutritional
      stress varied with time, with the difference of starvation resistance between
      optimally and suboptimally fed mosquitoes increasing from spring to summer, as
      shown by a significant interaction between diet treatment and months of capture.
      Infected and uninfected mosquitoes had similar clutch size, indicating no effect
      of infection on fecundity. Overall, this study suggests that avian malaria
      vectors may suffer Plasmodium infection costs in their natural habitat, under
      certain environmental conditions. This may have major implications for disease
      transmission in the wild. 

PMID- 24286466
TI  - Insulin on hydrogen peroxide-induced oxidative stress involves ROS/Ca2+ and
      Akt/Bcl-2 signaling pathways.
AB  - Oxidative stress is induced by excess accumulation of reactive oxygen and
      nitrogen species (RONS). Astrocytes are metabolically active cells in the brain
      and understanding astrocytic responses to oxidative stress is essential to
      understand brain pathologies. In addition to direct oxidative stress, exogenous
      hydrogen peroxide (H2O2) can penetrate biological membranes and enhance formation
      of other RONS. The present study was carried out to examine the role of insulin
      in H2O2-induced oxidative stress in rat astrocytic cells. To measure changes in
      the viability of astrocytes at different concentrations of H2O2 for 3 h, a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-based assay was used
      and 500 MUM H2O2 was selected to establish a model of H2O2-induced oxidative
      stress. Further assays showed that 3 h of 500 MUM H2O2-induced significant
      changes in the levels of lactate dehydrogenase (LDH), reactive oxygen species
      (ROS) and calcium ion (Ca(2+)) in C6 cells, with insulin able to effectively
      diminish H2O2-induced oxidative damage to C6 cells. Western blotting studies
      showed that insulin treatment of astrocytes increased the levels of
      phosphorylated Akt and magnified the decrease in total Bcl-2 protein. The
      protective effect of insulin treatment on H2O2-induced oxidative stress in
      astrocytes by reducing apoptosis may relate to the PI3K/Akt pathway.

PMID- 24286467
TI  - An analysis of the dermatological uses of mycophenolate mofetil in a tertiary
      hospital.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is increasingly being used by
      dermatologists to treat various skin conditions, but limited evidence exists
      regarding its efficacy. OBJECTIVE: To evaluate safety and efficacy of MMF in the
      treatment of dermatological conditions. METHODS: A retrospective chart review of
      all the dermatology patients treated with MMF between October 1999 and July 2008
      at a university-based teaching hospital in Australia. RESULTS: Sixty-nine
      patients included 43 females (62%) and 26 males. Nineteen patients (27%) achieved
      complete remission (CR) and 14 (20%) had no response to therapy. The average
      duration of treatment was 18.4 months and the mean daily dose was 2 g. Thirty-two
      patients (47%) experienced side effects, though most were mild. Factors
      influencing response to MMF were studied, and older age (p=0.005), diagnosis
      (p=0.008) and duration of treatment (p=0.02) were found significant. In a
      multivariate analysis, only the diagnosis remained statistically significant.
      There was a differential response to MMF between the various dermatological
      disorders studied. Complete response was achieved in 56%, 53% and 46% of the
      patients with atopic dermatitis (AD), immunobullous disorders and neutrophilic
      dermatoses, respectively, while none of the patients with psoriasis achieved CR.
      CONCLUSION: Our study shows that MMF is more effective in AD and immunobullous
      disorders than in psoriasis and pyoderma gangrenosum.

PMID- 24286468
TI  - The maize brown midrib2 (bm2) gene encodes a methylenetetrahydrofolate reductase
      that contributes to lignin accumulation.
AB  - The midribs of maize brown midrib (bm) mutants exhibit a reddish-brown color
      associated with reductions in lignin concentration and alterations in lignin
      composition. Here, we report the mapping, cloning, and functional and biochemical
      analyses of the bm2 gene. The bm2 gene was mapped to a small region of chromosome
      1 that contains a putative methylenetetrahydrofolate reductase (MTHFR) gene,
      which is down-regulated in bm2 mutant plants. Analyses of multiple Mu-induced bm2
      Mu mutant alleles confirmed that this constitutively expressed gene is bm2. Yeast
      complementation experiments and a previously published biochemical
      characterization show that the bm2 gene encodes a functional MTHFR. Quantitative
      RT-PCR analyses demonstrated that the bm2 mutants accumulate substantially
      reduced levels of bm2 transcript. Alteration of MTHFR function is expected to
      influence accumulation of the methyl donor S-adenosyl-L-methionine (SAM). Because
      SAM is consumed by two methyltransferases in the lignin pathway (Ye et al., ),
      the finding that bm2 encodes a functional MTHFR is consistent with its lignin
      phenotype. Consistent with this functional assignment of bm2, the expression
      patterns of genes in a variety of SAM-dependent or -related pathways, including
      lignin biosynthesis, are altered in the bm2 mutant. Biochemical assays confirmed
      that bm2 mutants accumulate reduced levels of lignin with altered composition
      compared to wild-type. Hence, this study demonstrates a role for MTHFR in lignin
      biosynthesis.

PMID- 24286469
TI  - Adipose tissue trans-fatty acids and changes in body weight and waist
      circumference.
AB  - Previous studies have suggested that the intake of trans-fatty acids (TFA) plays
      a role in the development of obesity. The proportions of adipose tissue fatty
      acids not synthesised endogenously in humans, such as TFA, usually correlate well
      with the dietary intake. Hence, the use of these biomarkers may provide a more
      accurate measure of habitual TFA intake than that obtained with dietary
      questionnaires. The objective of the present study was to investigate the
      associations between the proportions of specific TFA in adipose tissue and
      subsequent changes in weight and waist circumference (WC). The relative content
      of fatty acids in adipose tissue biopsies from a random sample of 996 men and
      women aged 50-64 years drawn from a Danish cohort study was determined by GC.
      Baseline data on weight, WC and potential confounders were available together
      with information on weight and WC 5 years after enrolment. The exposure measures
      were total trans-octadecenoic acids (18:1t), 18:1 Delta6-10t, vaccenic acid (18:1
      Delta11t) and rumenic acid (18:2 Delta9c, 11t). Data were analysed using multiple
      regression with cubic spline modelling. The median proportion of total adipose
      tissue 18:1t was 1.52% (90% central range 0.98, 2.19) in men and 1.47% (1.01,
      2.19) in women. No significant associations were observed between the proportions
      of total 18:1t, 18:1 Delta6-10t, vaccenic acid or rumenic acid and changes in
      weight or WC. The present study suggests that the proportions of specific TFA in
      adipose tissue are not associated with subsequent changes in weight or WC within
      the exposure range observed in this population.

PMID- 24286470
TI  - Comparative secretome analysis of Trichoderma asperellum S4F8 and Trichoderma
      reesei Rut C30 during solid-state fermentation on sugarcane bagasse.
AB  - BACKGROUND: The lignocellulosic enzymes of Trichoderma species have received
      particular attention with regard to biomass conversion to biofuels, but the
      production cost of these enzymes remains a significant hurdle for their
      commercial application. In this study, we quantitatively compared the
      lignocellulolytic enzyme profile of a newly isolated Trichoderma asperellum S4F8
      strain with that of Trichoderma reesei Rut C30, cultured on sugarcane bagasse
      (SCB) using solid-state fermentation (SSF). RESULTS: Comparison of the
      lignocellulolytic enzyme profiles of S4F8 and Rut C30 showed that S4F8 had
      significantly higher hemicellulase and beta-glucosidase enzyme activities. Liquid
      chromatography tandem mass spectrometry analysis of the two fungal secretomes
      enabled the detection of 815 proteins in total, with 418 and 397 proteins being
      specific for S4F8 and Rut C30, respectively, and 174 proteins being common to
      both strains. In-depth analysis of the associated biological functions and the
      representation of glycoside hydrolase family members within the two secretomes
      indicated that the S4F8 secretome contained a higher diversity of main and side
      chain hemicellulases and beta-glucosidases, and an increased abundance of some of
      these proteins compared with the Rut C30 secretome. CONCLUSIONS: In SCB SSF, T.
      asperellum S4F8 produced a more complex lignocellulolytic cocktail, with enhanced
      hemicellulose and cellobiose hydrolysis potential, compared with T. reesei Rut
      C30. This bodes well for the development of a more cost-effective and efficient
      lignocellulolytic enzyme cocktail from T. asperellum for lignocellulosic
      feedstock hydrolysis.

PMID- 24286471
TI  - The Sputum Colour Chart as a predictor of lung inflammation, proteolysis and
      damage in non-cystic fibrosis bronchiectasis: a case-control analysis.
AB  - BACKGROUND AND OBJECTIVE: Non-cystic fibrosis bronchiectasis (NCFB) is
      characterized by a vicious cycle of airway infection, inflammation and structural
      damage with inappropriate mucus clearance. Our aim was to relate the value of
      proteolytic enzymes, proteolytic enzyme activity and inflammatory markers to
      disease severity and symptoms in patients with NCFB. METHODS: Sputum induction in
      NCFB patients and healthy controls was performed. Sputum was analysed for total
      and differential cell count, markers of inflammation (CXCL8 (also known as
      interleukin-8) and tumour necrosis factor-alpha (TNF-alpha)) and proteolytic
      enzymes (neutrophil elastase (NE), gelatin zymography and total gelatinolytic
      activity (TGA)). Each patient was evaluated by spirometry, Leicester Cough
      Questionnaire (LCQ) and Sputum Colour Chart (SCC). Patient files were analysed to
      determine Pseudomonas aeruginosa colonization status. The computed tomography
      (CT) closest to the date sputum induction was scored by a radiologist. RESULTS:
      NCFB patients showed significantly higher neutrophils, CXCL8, TNF-alpha, NE and
      TGA than healthy controls. TGA subanalysis showed that the majority of the
      activity was NE (82 +/- 6.4%). Residual activity was mainly zinc ion-dependent
      matrix metalloproteinase (MMP) activity (18 +/- 6.4%). Subanalysis showed that
      patients with chronic Pseudomonas aeruginosa colonization had more activated MMP
      9. Correlations were seen between proteolytic enzymes and inflammation and
      disease severity (spirometry and CT score), but not with the LCQ. SCC was
      associated with increased markers of inflammation, proteolytic enzymes and worse
      CT score. CONCLUSIONS: We show that sputum purulence assessment in daily clinical
      practice using the SCC is a quick and easy tool that reflects severity of
      inflammation, destruction and proteolytic enzymatic activity/presence.

PMID- 24286472
TI  - Discontinuation of adalimumab after attaining disease activity score 28
      erythrocyte sedimentation rate remission in patients with rheumatoid arthritis
      (HONOR study): an observational study.
AB  - INTRODUCTION: Evidences of biologics-free disease control after discontinuing
      adalimumab (ADA) in rheumatoid arthritis (RA) patients in clinical practice have
      not been sufficiently investigated. Purpose of this study is to investigate
      whether disease activity score 28 (DAS28)- erythrocyte sedimentation rate (ESR)
      remission was preserved after discontinuation of ADA in patients with RA.
      METHODS: This is an observational but not a randomized controlled study. Among
      197 RA patients who initiated with combination of ADA with concomitant MTX, 69
      (35%) acquired DAS28 (ESR) < 2.6 for at least 24 weeks. Of those 69 patients, 51
      went on ADA discontinuation with their consent, and finally 50 of those with
      follow-up of > 24 weeks were evaluated. The effect of discontinuing ADA on
      clinical disease activity, functional disability and radiographic progression
      were evaluated by DAS28 (ESR), the clinical disease activity index (CDAI) and the
      simplified disease activity index (SDAI), by a health assessment questionnaire
      disability index (HAQ-DI) and by the modified total Sharp score (mTSS),
      respectively. RESULTS: The mean age of the participants was 59.5 years with the
      mean disease duration of 7.1 years. Out of the 50 patients, 29 (58%) were
      maintained in DAS28 (ESR) < 2.6 at 24 weeks after discontinuing ADA. A logistic
      regression analysis showed that DAS28 (ESR) at baseline significantly predicted a
      DAS28 (ESR) < 2.6 maintained after discontinuation of ADA, and a receiver
      operating characteristic (ROC) analysis showed that the cut-off value of DAS28
      (ESR) at discontinuation was 2.16. The mean HAQ-DI at six months after
      discontinuing ADA was 0.1 in patients who kept in DAS28 (ESR) < 2.6, and 94.9%
      (37/39) showed no evidence of radiographic progression (> 0.5 per year of a
      change in mTSS) at 1 year. CONCLUSIONS: It was possible to maintain DAS28 (ESR) <
      2.6 after discontinuation of ADA without functional and radiographic progression
      and very low DAS28 (ESR) at the discontinuation was associated with successful
      ADA-free DAS28 (ESR) < 2.6 in patients with RA. TRIAL REGISTRATION: University
      Hospital Medical Information Network Identifier: UMIN000006669.

PMID- 24286473
TI  - Antenatal and postnatal combined therapy for autoantibody-related congenital
      atrioventricular block.
AB  - BACKGROUND: Autoantibody-related congenital heart block (CHB) is an autoimmune
      condition in which trans placental passage of maternal autoantibodies cause
      damage to the developing heart conduction system of the foetus. CASE
      PRESENTATION: We report a case of an Italian 31-year-old woman, in a good
      clinical status, referred to our Centre at 26 weeks of her first pregnancy,
      because of foetal bradycardia, found during routine foetal ultrasonography.
      Foetal echocardiography revealed a 3rd degree CHB, without any anatomical
      defects. Despite the mother was asymptomatic for autoimmune disease, anti-Ro/La
      were searched for, because of the hypothesis of autoantibody-related CHB. High
      title of maternal anti-Ro/SSA antibodies was found and diagnosis of an
      autoantibody-related CHB was made. A combination treatment protocol of the mother
      was started with oral betamethasone, plasmapheresis and IVIG. An emergency C
      section was performed at 32 + 3 weeks of gestation because of a non-reassuring
      cardiotocography pattern. A male newborn (BW 1515 g, NGA, Apgar 8-10) was treated
      since birth with high-flow O2 for mild RDS. IVIG administration was started at
      one week, and then every two weeks, until complete disappearance of maternal
      antibodies from blood. Because of persistent low ventricular rate (<60/min),
      seven days following birth, pacemaker implantation was performed. The baby is now
      at 40th week with no signs of cardiac failure and free of any medications.
      CONCLUSION: Up to date, no guidelines have been published for the treatment of
      "in utero-CHB" and only anecdotal reports are available. It has been stated that
      a combination therapy protocol is effective in reversing a 2nd degree CHB, but
      not for 3rd degree CHB. In cases of foetal bradycardia, weekly foetal
      echocardiographic monitoring needs to be performed and in cases of 2nd degree CHB
      and 3rd degree CHB maternal therapy could be suggested, as in our case, to avoid
      foetal heart failure. In cases of 3rd degree CHB often pacemaker implantation is
      needed.

PMID- 24286474
TI  - Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope
      and risk of future rheumatoid arthritis: a nested case-control study.
AB  - INTRODUCTION: The aim of this study was to characterize anti-citrullinated
      peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with
      and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. METHODS: We
      identified 192 women in the Nurses' Health Study cohorts with blood samples
      obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis.
      Three controls were selected matched on age, cohort, menopausal status and post
      menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom
      BioPlex platform. We used conditional logistic regression to calculate the
      relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive
      and examined RRs by time between blood draw and RA onset. Measures of
      multiplicative and additive interaction between any ACPA-positive and HLA-SE were
      calculated. RESULTS: All ACPAs by peptide groups were significantly associated
      with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA
      varied over time with the strongest association in those with blood draw less
      than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or
      more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA
      SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases
      showed reactivity to more ACPA types than HLA-SE negative (chi2 test for trend, P
      = 0.01). CONCLUSIONS: There is increasing ACPA reactivity up to 10 years before
      RA onset with the strongest association within 5 years of RA onset. The magnitude
      of the response to ACPAs, in combination with the presence of HLA-SE, is most
      important for identifying those individuals with the highest risk of RA.

PMID- 24286476
TI  - Family influence.

PMID- 24286477
TI  - Diversity and structure of bacterial communities associated with Phanerochaete
      chrysosporium during wood decay.
AB  - Wood recycling is key to forest biogeochemical cycles, largely driven by
      microorganisms such as white-rot fungi which naturally coexist with bacteria in
      the environment. We have tested whether and to what extent the diversity of the
      bacterial community associated with wood decay is determined by wood and/or by
      white-rot fungus Phanerochaete chrysosporium. We combined a microcosm approach
      with an enrichment procedure, using beech sawdust inoculated with or without
      P.chrysosporium. During 18 weeks, we used 16S rRNA gene-based pyrosequencing to
      monitor the forest bacterial community inoculated into these microcosms. We found
      bacterial communities associated with wood to be substantially less diverse than
      the initial forest soil inoculum. The presence of most bacterial operational
      taxonomic units (OTUs) varied over time and between replicates, regardless of
      their treatment, suggestive of the stochastic processes. However, we observed two
      OTUs belonging to Xanthomonadaceae and Rhizobium, together representing 50% of
      the relative bacterial abundance, as consistently associated with the wood
      substrate, regardless of fungal presence. Moreover, after 12 weeks, the bacterial
      community composition based on relative abundance was significantly modified by
      the presence of the white-rot fungus. Effectively, members of the Burkholderia
      genus were always associated with P.chrysosporium, representing potential
      taxonomic bioindicators of the white-rot mycosphere.

PMID- 24286475
TI  - Involvement of the Notch pathway in terminal astrocytic differentiation: role of
      PKA.
AB  - The Notch pathway is a highly conserved signaling system essential for modulating
      neurogenesis and promoting astrogenesis. Similarly, the cAMP signaling cascade
      can promote astrocytic commitment in several cell culture models, such as the C6
      glioma cell line. These cells have the capacity to differentiate into
      oligodendrocytes or astrocytes, characteristics that allow their use as a glial
      progenitor model. In this context, we explore here the plausible involvement of
      cAMP in Notch-dependent signal transactions. The exposure of C6 cells to a non
      hydrolysable cAMP analogue resulted in a sustained augmentation of Notch
      activity, as detected by nuclear translocation of its intracellular domain
      portion (NICD) and transcriptional activity. The cAMP effect is mediated through
      the activation of the gamma-secretase complex, responsible for Notch cleavage and
      is sensitive to inhibitors of the cAMP-dependent protein kinase, PKA. As
      expected, Notch cleavage and nuclear translocation resulted in the up-regulation
      of the mRNA levels of one of its target genes, the transcription factor Hair and
      enhancer of split 5. Moreover, the glutamate uptake activity, as well as the
      expression of astrocytic markers such as glial fibrillary acidic protein,
      S100beta protein and GLAST was also enhanced in cAMP-exposed cells. Our results
      clearly suggest that during the process of C6 astrocytic differentiation, cAMP
      activates the PKA/gamma-secretase/NICD/RBPJ(kappa) pathway and Notch1 expression,
      leading to transcriptional activation of the genes responsible for glial
      progenitor cell fate decision.

PMID- 24286478
TI  - Multivalent paediatric allergy vaccines protect against allergic anaphylaxis in
      mice.
AB  - BACKGROUND: Almost a quarter of the world population suffers from IgE-mediated
      allergies. T cells and IgG-producing B cells can produce protection, but
      treatment for disease is laborious with unsatisfactory patient compliance.
      OBJECTIVE: We sought to identify whether paediatric allergy vaccines affected
      later allergen sensitization and onset of disease when used prophylactically.
      METHODS: A murine model of anaphylaxis was applied. Mice were first immunized
      with monovalent or multivalent allergy vaccines that also contained aluminium
      hydroxide and CpG oligodeoxynucleotide as adjuvants. Later, the mice were
      sensitized by multiple low-dose injections of aluminium-adsorbed allergen. After
      a dormant period, the mice were challenged systemically with high-dose allergen,
      and the clinical signs of anaphylaxis were recorded. Throughout the immunization
      and sensitization periods, blood was collected for serological testing. RESULTS:
      Immunization with allergy vaccines produced antigen-specific protection against
      sensitization as measured by systemic anaphylaxis in mice. The long-term effect
      was observed both after juvenile (5-6 weeks) and neonatal (7 days) vaccination.
      Monovalent and pentavalent vaccines were protective to a similar level.
      Protection was associated with increased secretion of IgG2a and production of IFN
      gamma. Protection could also be transferred to sensitized mice via serum or via
      CD25-positive CD4 T cells. CONCLUSION AND CLINICAL RELEVANCE: Prophylactic and
      multivalent allergy vaccines in juvenile and neonatal mice protected against
      later sensitization and anaphylaxis. Such treatment may provide a rational
      measure for future management of allergen-related diseases and their strong socio
      economic impact on daily life.

PMID- 24286480
TI  - From small studies to precision medicine: prioritizing candidate biomarkers.
AB  - There are still many open questions in data-analytic research pertaining to
      biomarker development in the era of personalized/precision medicine and big data.
      Among them is the question of what constitutes best practice for the extraction
      of prioritized lists of candidate biomarkers from smaller studies that are
      'hypothesis generating' in nature. A recent comparison of methods to detect
      patient-specific aberrant expression events in small- to medium-sized (10 to 50
      samples) studies provides results that favor the use of outlying degree methods.
      See related Research, http://genomemedicine.com/content/5/11/103. 

PMID- 24286479
TI  - Interpreting genetics in the context of eating disorders: evidence of disease,
      not diversity.
AB  - How is genetic involvement interpreted for disorders whose medicalisation is
      contested? Framing psychiatric and behavioural disorders in terms of genetics is
      expected to make them seem more medical. Yet a genetic aetiology can also be used
      to frame behaviour as acceptable human variation, rather than a medical problem
      (for example, sexual orientation). I analyse responses to the idea that there is
      a genetic component in anorexia and bulimia nervosa (AN or BN) via semi
      structured interviews with a sample of 50 women diagnosed with an eating disorder
      (25 had recovered). All but three volunteered that genetics would medicalise AN
      or BN by (i) making eating disorders seem more like 'real diseases'; implying
      that these disorders need (ii) professional treatment or (iii) a biologically
      based treatment. The results also indicate there are several counter-logics by
      which genetic framing could support non-medical definitions of AN or BN. I argue
      that genetic framing reduces perceived individual responsibility, which can
      support definitions of behaviour as either a reflection of disease (which entails
      intervention) or a reflection of normal human diversity (which does not). In the
      context of public scepticism as to the 'reality' of AN or BN, genetic involvement
      was taken as evidence of disease in ongoing negotiations about the medical and
      moral status of people with eating disorders.

PMID- 24286481
TI  - Are self-efficacy beliefs and subjective task demand related to apathy in aging?
AB  - OBJECTIVE: Apathy, defined as a reduction in voluntary goal-directed behaviors
      (GDBs), is common in aging, but the processes underlying apathy are still
      unclear. Self-efficacy beliefs are likely to play a key role in GDBs, by
      influencing goal setting, perceived difficulty, and the necessary amount of
      effort to achieve goals. The aim of this study was to examine the relationships
      between apathy and perceived self-efficacy. METHOD: Sixty-three healthy elderly
      participants worked on a memory task without fixed performance standard ('do your
      best') and indicated perceived difficulty and effort investment after performing
      the task. They also completed two short scales assessing general self-efficacy
      and negative mood. In addition, a close relative of each participant completed
      the Initiative Interest Scale, a new questionnaire assessing apathetic
      manifestations in aging. RESULTS: The main results showed that subjective task
      demand (i.e., perceived difficulty and estimated effort) operated as a mediator
      between self-efficacy beliefs and apathy. These results suggest that elderly
      people with low self-efficacy beliefs who face a challenge judge the task to be
      highly difficult and effort demanding, which might result in GDB reduction.
      CONCLUSION: These results shed new light on the processes related to apathy in
      aging and open up an interesting prospect for psychological interventions.

PMID- 24286482
TI  - A prospective randomized trial comparing tension-free vaginal tape versus
      transobturator tape in patients with stress or mixed urinary incontinence:
      subjective cure rate and satisfaction in median follow-up of 46 months.
AB  - OBJECTIVE: The aim of this study was to investigate the difference in subjective
      cure rate and patient satisfaction between tension-free vaginal tape (TVT) and
      transobturator tape (TOT) surgical methods in the treatment of stress and mixed
      urinary incontinence. MATERIAL AND METHODS: From January 2004 to November 2006, a
      total of 100 patients suffering from stress or mixed urinary incontinence and
      evaluated to benefit from operative treatment were randomized to undergo either
      TVT or TOT surgery in Oulu University Hospital. There were no significant
      differences between the study groups concerning the patient characteristics.
      During the 3, 14 and 46 month follow-up steps, information on subjective cure and
      patient satisfaction was gathered with Urinary Incontinence Severity Score and
      Detrusor Instability Score questionnaires and a specific question about
      satisfaction. RESULTS: The subjective cure rate was 81% in both study groups. The
      satisfaction rate was 79% in the TVT group and 74% in the TOT group at the final
      follow-up. Urge symptoms were relieved in 70% of patients in the mixed urinary
      incontinence subgroup. De novo urgency occurred in 17% of the patients in the
      stress urinary incontinence subgroup, and 45% of these patients were unsatisfied
      after the follow-up. CONCLUSIONS: TVT and TOT are equally effective methods in
      the treatment of urinary incontinence and patient satisfaction is similar in both
      methods. A large proportion of patients with mixed urinary incontinence found the
      operation beneficial for urge symptoms.

PMID- 24286483
TI  - Evidence for linkage of migraine in Rolandic epilepsy to known 1q23 FHM2 and
      novel 17q22 genetic loci.
AB  - Migraine headaches are a common comorbidity in Rolandic epilepsy (RE) and
      familial aggregation of migraine in RE families suggests a genetic basis not
      mediated by seizures. We performed a genome-wide linkage analysis of the migraine
      phenotype in 38 families with RE to localize potential genetic contribution, with
      a follow-up in an additional 21 families at linked loci. We used two-point and
      multipoint LOD (logarithm of the odds) score methods for linkage, maximized over
      genetic models. We found evidence of linkage to migraine at chromosome 17q12-22
      [multipoint HLOD (heterogeneity LOD) 4.40, recessive, 99% penetrance], replicated
      in the second dataset (HLOD 2.61), and suggestive evidence at 1q23.1-23.2,
      centering over the FHM2 locus (two-point LOD 3.00 and MP HLOD 2.52). Sanger
      sequencing in 14 migraine-affected individuals found no coding mutations in the
      FHM2 gene ATP1A2. There was no evidence of pleiotropy for migraine and either
      reading or speech disorder, or the electroencephalographic endophenotype of RE
      when the affected definition was redefined as those with migraine or the comorbid
      phenotype, and pedigrees were reanalyzed for linkage. In summary, we report a
      novel migraine susceptibility locus at 17q12-22, and a second locus that may
      contribute to migraine in the general population at 1q23.1-23.2. Comorbid
      migraine in RE appears genetically influenced, but we did not obtain evidence
      that the identified susceptibility loci are consistent with pleiotropic effects
      on other comorbidities in RE. Loci identified here should be fine-mapped in
      individuals from RE families with migraine, and prioritized for analysis in other
      types of epilepsy-associated migraine. 

PMID- 24286484
TI  - Multiple aspects of plasticity in clutch size vary among populations of a
      globally distributed songbird.
AB  - Plasticity in life-history characteristics can influence many ecological and
      evolutionary phenomena, including how invading organisms cope with novel
      conditions in new locations or how environmental change affects organisms in
      native locations. Variation in reaction norm attributes is a critical element to
      understanding plasticity in life history, yet we know relatively little about the
      ways in which reaction norms vary within and among populations. We amassed data
      on clutch size from marked females in eight populations of house sparrows (Passer
      domesticus) from North America and Europe. We exploited repeated measures of
      clutch size to assess both the extent of within-individual phenotypic plasticity
      and among-individual variation and to test alternative hypotheses about the
      underlying causes of reaction norm shape, particularly the decline in clutch size
      with date. Across all populations, females of this multibrooded species altered
      their clutch size with respect to date, attempt order, and the interaction of
      date and order, producing a reaction norm in multidimensional environmental
      space. The reaction norm fits that predicted by a model in which optimal clutch
      size is driven by a decline with date hatched in the ability of offspring to
      recruit. Our results do not fit those predicted for other proposed causes of a
      seasonal decline in clutch size. We also found significant differences between
      populations in response to date and the date by attempt order interaction. We
      tested the prediction that the relationship with date should be increasingly
      negative as breeding season becomes shorter but found steeper declines in clutch
      size with date in populations with longer seasons, contrary to the prediction.
      Populations also differed in the level of among-individual variation in reaction
      norm intercept, but we found no evidence of among-individual variation in
      reaction norm slope. We show that complex reaction norms in life-history
      characters exhibit within- and among-population variance. The nature of this
      variance is only partially consistent with current life-history theory and
      stimulates expansions of such theory to accommodate complexities in adaptive life
      history. 

PMID- 24286485
TI  - Proteomic profiling and functional characterization of early and late shoulder
      osteoarthritis.
AB  - INTRODUCTION: The development of effective treatments for osteoarthritis (OA) has
      been hampered by a poor understanding of OA at the cellular and molecular levels.
      Emerging as a disease of the 'whole joint', the importance of the biochemical
      contribution of various tissues, including synovium, bone and articular
      cartilage, has become increasingly significant. Bathing the entire joint
      structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic
      shoulders offers a valuable 'snapshot' of the biologic environment throughout
      disease progression. The purpose of this study was to identify differentially
      expressed proteins in early and late shoulder osteoarthritic SF in comparison to
      healthy SF. METHODS: A quantitative 18O labeling proteomic approach was employed
      to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA
      patients compared to control individuals (n = 5). In addition, ELISA was used to
      quantify six pro-inflammatory and two anti-inflammatory cytokines. RESULTS: Key
      results include a greater relative abundance of proteins related to the
      complement system and the extracellular matrix in SF from both early and late OA.
      Pathway analyses suggests dysregulation of the acute phase response, liver x
      receptor/retinoid x receptor (LXR/RXR), complement system and coagulation
      pathways in both early and late OA. The network related to lipid metabolism was
      down-regulated in both early and late OA. Inflammatory cytokines including
      interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA.
      CONCLUSIONS: The results suggest a dysregulation of wound repair pathways in
      shoulder OA contributing to the presence of a 'chronic wound' that progresses
      irreversibly from early to later stages of OA. Protease inhibitors were
      downregulated in late OA suggesting uncontrolled proteolytic activity occurring
      in late OA. These results contribute to the theory that protease inhibitors
      represent promising therapeutic agents which could limit proteolytic activity
      that ultimately leads to cartilage destruction.

PMID- 24286486
TI  - Clinical implementation of genetic testing in medicine: a US regulatory science
      perspective.
AB  - Heterogeneity of treatment effects in unselected patient populations has
      stimulated various strategic approaches to reduce variability and uncertainty and
      improve individualization of drug selection and dosing. The rapid growth of DNA
      sequencing and related technologies has ramped up progress in interpreting
      germline and somatic mutations and has begun to reshape medicine, especially in
      oncology. Over the past decade, regulatory agencies realized that they needed to
      be proactive and not reactive if personalized medicine was to become a reality.
      The US Food and Drug Administration, in particular, took steps to nurture the
      field through peer-reviewed publications, co-sponsoring public workshops and
      issuing guidance for industry. The following two major approaches to personalized
      medicine were taken: (i) encouragement of de novo co-development of drug-genetic
      test combinations by industry; and (ii) retrospective assessment of legacy
      genetic data for the purpose of updating drug labels. The former strategy has
      been more successful in getting new targeted therapies to the marketplace with
      successful adoption, while the latter, as evidenced by the low adoption rate of
      pharmacogenetic testing, has been less successful. This reflection piece makes
      clear that several important things need to happen to make personalized medicine
      diffuse in more geographical areas and among more therapeutic specialties. The
      debate over clinical utility of genetic tests needs to be resolved with consensus
      on evidentiary standards. Physicians, as gatekeepers of prescription medicines,
      need to increase their knowledge of genetics and the application of the
      information to patient care. An infrastructure needs to be developed to make
      access to genetic tests and decision-support tools available to primary
      practitioners and specialists outside major medical centres and metropolitan
      areas. 

PMID- 24286487
TI  - Concurrent partnering and condom use among rural heterosexual African-American
      men.
AB  - Background Limited research has targeted HIV risk among heterosexual African
      American men in the rural south-eastern United States. METHODS: A cross-sectional
      survey was administered to 538 men to assess HIV knowledge, attitudes towards HIV
      testing and sexual risk behaviour. RESULTS: Fifty-one percent reported consistent
      condom use in the past 3 months. Monogamous men reported more consistent condom
      use (t=3.47, d.f.=536, P<0.001). In concurrent partnerships, condom use was
      inversely related to age (adjusted odds ratio (AOR)=0.98, 95% confidence interval
      (CI)=0.95-0.998, P=0.03) and increased with the number of female partners
      (AOR=1.49, 95% CI=1.26-1.76, P<0.001). CONCLUSIONS: African-American HIV
      prevention outreach should include focus on concurrent partnering in rural
      settings.

PMID- 24286488
TI  - Australian gay and bisexual men's use of erectile dysfunction medications during
      recent sexual encounters.
AB  - AIM: Use of erectile dysfunction medications (EDMs) is relatively common among
      gay and bisexual men and has been associated with human immunodeficiency virus
      sexual risk behavior. We aimed to determine what factors were related to EDM use
      on occasions when participants engaged in protected anal intercourse (PAIC) and
      when they engaged in unprotected anal intercourse (UAIC) with casual partners.
      METHODS: An online cross-sectional survey was conducted, resulting in a sample of
      1,376 Australian gay and bisexual men who reported an occasion of anal
      intercourse with casual male partners in the previous year. MAIN OUTCOME MEASURE:
      The main outcome measure was the use of EDM during most recent occasions of PAIC
      and UAIC. RESULTS: Men were as likely to use EDM on occasions when they were
      using condoms (11.6%) as they were on occasions when they did not use condoms
      (13.0%). There was no association between use of EDM and self-esteem, nor was
      there an association between sexual risk behavior and self-esteem. Men who used
      EDM were more sexually active overall and appeared to often use EDM to enhance
      and extend their sexual experiences. CONCLUSIONS: Men did not appear to use EDM
      specifically for the purposes of risk-taking and mainly used EDM to enhance
      sexual pleasure. Mental health issues were not indicated by use of EDM.

PMID- 24286489
TI  - Intravesical hyaluronidase causes chronic cystitis in a rat model: a potential
      model of bladder pain syndrome/interstitial cystitis.
AB  - OBJECTIVES: To determine whether a potential rat model of bladder pain syndrome
      could be developed through long-term intermittent intravesical hyaluronidase.
      METHODS: A total of 64 female Sprague-Dawley rats were divided into a control
      group, a low-dose hyaluronidase (1 mg/mL) group, a high-dose hyaluronidase (4
      mg/mL) group and a hyaluronic acid-treated group. Hyaluronidase was given
      intravesically three times a week for 1 month. Hyaluronic acid (0.5 mL, 0.8
      mg/mL) was introduced intravesically to hyaluronidase-treated rats' bladders.
      Histological changes, cystometry, nociceptive behaviors, and messenger
      ribonucleic acid levels of inflammatory factors were evaluated and compared
      between groups. RESULTS: All hyaluronidase-treated rats showed chronic
      inflammation and fibrosis, increased and activated mast cells, thinned bladder
      epithelium with abnormal expressions of uroplakin III and zonula occluden-1, and
      increased levels of interleukin-6 and intercellular adhesion molecule-1 messenger
      ribonucleic acid. However, the inflammatory score and levels of interleukin-6 and
      intercellular adhesion molecule-1 were more significant in the high-dose
      hyaluronidase group than in the low-dose hyaluronidase group (P < 0.01).
      Furthermore, hyaluronidase-treated rats showed markedly decreased
      intercontraction intervals, bladder capacity and increased sensitivity to pain
      compared with controls (P < 0.01). Hyaluronic acid treatment significantly
      decreased the inflammatory level, number of mast cells, sensitivity to pain,
      levels of interleukin-6 and intercellular adhesion molecule-1, and increased
      intercontraction intervals and bladder capacity (P < 0.01). CONCLUSIONS: Long
      term intermittent intravesical hyaluronidase could develop a severe chronic
      cystitis with diffused fibrosis accompanied by altered histology and bladder
      function. This chronic cystitis rat model can resemble the clinical and
      histopathological features of human bladder pain syndrome, and might be a
      potential valuable model for investigation of this troublesome disease.

PMID- 24286490
TI  - Techno-economic potential of bioethanol from bamboo in China.
AB  - BACKGROUND: Bamboo is potentially an interesting feedstock for advanced
      bioethanol production in China due to its natural abundance, rapid growth,
      perennial nature and low management requirements. Liquid hot water (LHW)
      pretreatment was selected as a promising technology to enhance sugar release from
      bamboo lignocellulose whilst keeping economic and environmental costs to a
      minimum. The present research was conducted to assess: 1) by how much LHW
      pretreatment can enhance sugar yields in bamboo, and 2) whether this process has
      the potential to be economically feasible for biofuel use at the commercial
      scale. Pretreatments were performed at temperatures of 170-190 degrees C for 10
      30 minutes, followed by enzymatic saccharification with a commercial enzyme
      cocktail at various loadings. These data were then used as inputs to a techno
      economic model using AspenPlusTM to determine the production cost of bioethanol
      from bamboo in China. RESULTS: At the selected LHW pretreatment of 190 degrees C
      for 10 minutes, 69% of the initial sugars were released under a standardised
      enzyme loading; this varied between 59-76% when 10-140 FPU/g glucan of commercial
      enzyme Cellic CTec2 was applied. Although the lowest enzyme loading yielded the
      least amount of bioethanol, the techno-economic evaluation revealed it to be the
      most economically viable scenario with a production cost of $0.484 per litre
      (with tax exemption and a $0.16/litre subsidy). The supply-chain analysis
      demonstrated that bioethanol could be economically competitive with petrol at the
      pump at enzyme loadings up to 60 FPU/g glucan. However, in a prospective scenario
      with reduced government support, this enzyme loading threshold would be reduced
      to 30 FPU/g glucan. CONCLUSIONS: Bioethanol from bamboo is shown to be both
      technically and economically feasible, as well as competitive with petrol in
      China. Alternative approaches to reduce bioethanol production costs are still
      needed however, to ensure its competitiveness in a possible future scenario where
      neither tax exemptions nor subsidies are granted to producers. These measures may
      include improving sugar release with more effective pretreatments and reduced
      enzyme usage, accessing low cost bamboo feedstock or selecting feedstocks with
      higher/more accessible cellulose.

PMID- 24286491
TI  - Study on chemical constituents of Cyclocarya paliurus.
AB  - A new dammarane triterpenoid glycoside named cyclocarioside J (1) and other three
      known triterpenoid glycosides were isolated from the leaves of Cyclocarya
      paliurus. Based on ESI-MS, HR-ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR techniques
      including (1)H-(1)H COSY, HMBC, HMQC, and NOESY correlations, the structure of
      cyclocarioside J was elucidated as (20S,24R)-epoxydammarane 3beta,12beta,25
      trihydroxy-12-O-beta-d-quinovopyranosyl-3-O-alpha-l-arabinopyranoside. 

PMID- 24286492
TI  - Th17 and Th22 cells in psoriatic arthritis and psoriasis.
AB  - INTRODUCTION: The aim of this study was to characterize interleukin 17 (IL-17)
      and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin,
      synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and
      psoriatic arthritis (PsA). METHODS: Flow cytometry was used to enumerate cells
      making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12
      patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid
      arthritis (RA) patients were used as controls. Expression of the interleukin 23
      receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion
      of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical
      staining of IL-17 and IL-22. RESULTS: Increased frequencies of IL-17+ and IL-22+
      CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was
      significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in
      PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells
      making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+
      T cells were elevated in patients with Ps and those with PsA. In patients with
      PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB.
      Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps
      skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were
      seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower.
      Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL
      22 expression was higher in RA than either OA or PsA ST, in which IL-22 was
      strikingly absent. CONCLUSIONS: Elevated frequencies of IL-17 and IL-22 producing
      CD4+ T cells were a feature of both Ps and PsA. However their differing
      distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells
      in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that
      Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis
      of Ps and PsA.

PMID- 24286493
TI  - Reduced phototropism in pks mutants may be due to altered auxin-regulated gene
      expression or reduced lateral auxin transport.
AB  - Phototropism allows plants to orient their photosynthetic organs towards the
      light. In Arabidopsis, phototropins 1 and 2 sense directional blue light such
      that phot1 triggers phototropism in response to low fluence rates, while both
      phot1 and phot2 mediate this response under higher light conditions. Phototropism
      results from asymmetric growth in the hypocotyl elongation zone that depends on
      an auxin gradient across the embryonic stem. How phototropin activation leads to
      this growth response is still poorly understood. Members of the phytochrome
      kinase substrate (PKS) family may act early in this pathway, because PKS1, PKS2
      and PKS4 are needed for a normal phototropic response and they associate with
      phot1 in vivo. Here we show that PKS proteins are needed both for phot1- and
      phot2-mediated phototropism. The phototropic response is conditioned by the
      developmental asymmetry of dicotyledonous seedlings, such that there is a faster
      growth reorientation when cotyledons face away from the light compared with
      seedlings whose cotyledons face the light. The molecular basis for this
      developmental effect on phototropism is unknown; here we show that PKS proteins
      play a role at the interface between development and phototropism. Moreover, we
      present evidence for a role of PKS genes in hypocotyl gravi-reorientation that is
      independent of photoreceptors. pks mutants have normal levels of auxin and normal
      polar auxin transport, however they show altered expression patterns of auxin
      marker genes. This situation suggests that PKS proteins are involved in auxin
      signaling and/or lateral auxin redistribution. 

PMID- 24286494
TI  - Prevalence of dental erosion and association with lifestyle factors in Swedish 20
      year olds.
AB  - OBJECTIVE: To investigate the prevalence, distribution and severity of dental
      erosion and its association with lifestyle, oral and general health in young
      adults. MATERIALS AND METHODS: Four hundred and ninety-four individuals, 20-years
      of age, participated. Dental erosion in molars and maxillary incisors was
      evaluated. Caries, plaque and gingivitis were registered. Saliva samples were
      taken and the subjects were interviewed about behavioural and dietary habits and
      oral and general health. Body mass index (BMI) was calculated. The individuals
      were sub-divided into two groups according to the presence and absence of dental
      erosion: within the group with erosion was a sub-group of individuals with
      extensive erosion. RESULTS: Of the individuals 25% had no erosion, 75% had
      erosion and 18% had extensive erosion. Erosion was found in molars in 74% of the
      individuals and on buccal and palatal surfaces in maxillary incisors in 4% and
      7%, respectively. Cupping was seen in 65% of individuals and severe erosion in
      molars in 1.6%. Compared to subjects with no erosion, those with extensive
      erosion had a higher consumption of soft drinks (p = 0.05), caries prevalence (p
      < 0.01), prevalence of mutans Streptococci (p < 0.01) and BMI (p < 0.05).
      Furthermore, subjects with erosion had higher caries prevalence (p < 0.01) and
      BMI (p < 0.01) than those with no erosion. CONCLUSIONS: Swedish young adults have
      a high prevalence of dental erosion, but the level of severe erosion is low. The
      study disclosed a relationship between dental erosion and behavioural factors,
      oral health and BMI.

PMID- 24286495
TI  - Family history of cancer, personal history of medical conditions and risk of oral
      cavity cancer in France: the ICARE study.
AB  - BACKGROUND: The aim of this study was to evaluate the role of family history of
      cancer and personal history of other medical conditions in the aetiology of the
      oral cavity cancer in France. METHODS: We used data from 689 cases of oral cavity
      squamous cell carcinoma and 3481 controls included in a population-based case
      control study, the ICARE study. Odds-ratios (ORs) associated with family history
      of cancer and personal medical conditions and their 95% confidence intervals (95%
      CI) were estimated by unconditional logistic regression and were adjusted for
      age, gender, area of residence, education, body mass index, tobacco smoking and
      alcohol drinking. RESULTS: Personal history of oral candidiasis was related to a
      significantly increased risk of oral cavity cancer (OR 5.0, 95% CI 2.1-12.1).
      History of head and neck cancers among the first-degree relatives was associated
      with an OR of 1.9 (95% CI 1.2-2.8). The risk increased with the number of first
      degree relatives with head and neck cancer. CONCLUSION: A family history of head
      and neck cancer is a marker of an increased risk of oral cavity cancer and should
      be taken into account to target prevention efforts and screening. Further studies
      are needed to clarify the association between oral cavity cancer and personal
      history of candidiasis.

PMID- 24286497
TI  - A new HLA-A*01 allele - A*01:139.
AB  - HLA-A*01:139 differs from A*01:01:01:01 by one nucleotide (383G>C) resulting in
      an amino acid change of glycine104alanine. 

PMID- 24286496
TI  - Pathogenic Rickettsia species acquire vitronectin from human serum to promote
      resistance to complement-mediated killing.
AB  - Bacteria of the genus Rickettsia are transmitted from arthropod vectors and
      primarily infect cells of the mammalian endothelial system. Throughout this
      infectious cycle, the bacteria are exposed to the deleterious effects of serum
      complement. Using Rickettsia conorii, the etiologic agent of Mediterranean
      spotted fever (MSF), as a model rickettsial species, we have previously
      demonstrated that this class of pathogen interacts with human factor H to mediate
      partial survival in human serum. Herein, we demonstrate that R. conorii also
      interacts with the terminal complement complex inhibitor vitronectin (Vn). We
      further demonstrate that an evolutionarily conserved rickettsial antigen,
      Adr1/RC1281, interacts with human vitronectin and is sufficient to mediate
      resistance to serum killing when expressed at the outer-membrane of serum
      sensitive Escherichia coli. Adr1 is an integral outer-membrane protein whose
      structure is predicted to contain eight membrane-embedded beta-strands and four
      'loop' regions that are exposed to extracellular milieu. Site-directed
      mutagenesis of Adr1 revealed that at least two predicted 'loop' regions are
      required to mediate resistance to complement-mediatedkilling and vitronectin
      acquisition. These results demonstrate that rickettsial species have evolved
      multiple mechanisms to evade complement deposition and that evasion of killing in
      serum is an evolutionarily conserved virulence attribute for this genus of
      obligate intracellular pathogens. 

PMID- 24286498
TI  - Attempted suicide in a Xhosa schizophrenia and schizoaffective disorder
      population.
AB  - Suicide risk behavior is a significant contributor to the mortality and morbidity
      of schizophrenia. We previously reported affected sibship status in a Xhosa
      schizophrenia or schizoaffective disorder sample to be protective in nature;
      given the counterintuitive nature of this finding, we expanded the sample size to
      seek further clarification. Subjects were assessed with the Diagnostic Interview
      for Genetic Studies and then stratified into two groups: with (n = 137) or
      without (n = 837) a previous suicide attempt. The presence of lifetime bizarre
      behavior (OR 1.5; 95% CI 1.12-1.87) or cannabis use or abuse (OR 1.2; 95% CI
      10.01-1.47) was a significant predictor of suicide attempts, while a higher
      global alogia score (OR 0.84; 95% CI 0.74-0.96) was a protective factor. Our data
      seem to support that in this population, encouraging family members to report
      bizarre behavior and implementing dual diagnosis interventions for cannabis use
      or abuse could be an appropriate starting point toward developing a targeted
      suicide prevention program for further research.

PMID- 24286499
TI  - A DNA mini-barcode for land plants.
AB  - Small portions of the barcode region - mini-barcodes - may be used in place of
      full-length barcodes to overcome DNA degradation for samples with poor DNA
      preservation. 591,491,286 rbcL mini-barcode primer combinations were
      electronically evaluated for PCR universality, and two novel highly universal
      sets of priming sites were identified. Novel and published rbcL mini-barcode
      primers were evaluated for PCR amplification [determined with a validated
      electronic simulation (n = 2765) and empirically (n = 188)], Sanger sequence
      quality [determined empirically (n = 188)], and taxonomic discrimination
      [determined empirically (n = 30,472)]. PCR amplification for all mini-barcodes,
      as estimated by validated electronic simulation, was successful for 90.2-99.8% of
      species. Overall Sanger sequence quality for mini-barcodes was very low - the
      best mini-barcode tested produced sequences of adequate quality (B20 >= 0.5) for
      74.5% of samples. The majority of mini-barcodes provide correct identifications
      of families in excess of 70.1% of the time. Discriminatory power noticeably
      decreased at lower taxonomic levels. At the species level, the discriminatory
      power of the best mini-barcode was less than 38.2%. For samples believed to
      contain DNA from only one species, an investigator should attempt to sequence, in
      decreasing order of utility and probability of success, mini-barcodes F
      (rbcL1/rbcLB), D (F52/R193) and K (F517/R604). For samples believed to contain
      DNA from more than one species, an investigator should amplify and sequence mini
      barcode D (F52/R193).

PMID- 24286500
TI  - Lack of change in urate deposition by dual-energy computed tomography among
      clinically stable patients with long-standing tophaceous gout: a prospective
      longitudinal study.
AB  - INTRODUCTION: Dual-energy computed tomography (DECT) has potential for monitoring
      urate deposition in patients with gout. The aim of this prospective longitudinal
      study was to analyse measurement error of DECT urate volume measurement in
      clinically stable patients with tophaceous gout. METHODS: Seventy-three patients
      with tophaceous gout on stable therapy attended study visits at baseline and
      twelve months. All patients had a comprehensive clinical assessment including
      serum urate testing and DECT scanning of both feet. Two readers analysed the DECT
      scans for the total urate volume in both feet. Analysis included inter-reader
      intraclass correlation coefficients (ICCs) and limits of agreement, and
      calculation of the smallest detectable change. RESULTS: Mean (standard deviation)
      serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate
      lowering therapy was prescribed in 70 (96%) patients. The median (interquartile
      range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm(3), and change in DECT
      urate volume was -0.01 (-0.40, 0.28) cm(3). Inter-reader ICCs were 1.00 for
      baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard
      deviation) for baseline volumes was -0.18 (0.63) cm(3) and for change was -0.10
      (0.93) cm(3). The smallest detectable change was 0.91 cm3. There were 47 (64%)
      patients with baseline DECT urate volumes <0.91 cm(3). Higher serum urate
      concentrations were observed in patients with increased DECT urate volumes above
      the smallest detectable change (P = 0.006). However, a relationship between
      changes in DECT urate volumes and serum urate concentrations was not observed in
      the entire group. CONCLUSIONS: In patients with tophaceous gout on stable
      conventional urate-lowering therapy the measurement error for DECT urate volume
      assessment is substantially greater than the median baseline DECT volume.
      Analysis of patients commencing or intensifying urate-lowering therapy should
      clarify the optimal use of DECT as a potential outcome measure in studies of
      chronic gout.

PMID- 24286502
TI  - Identification of duck HSP70 gene, polymorphism analysis and tissue expression
      under control and heat stress conditions.
AB  - 1. This study was designed to characterise the duck heat shock protein 70 gene
      (HSP70) and identify sequence variation. 2. Chicken HSP70 sequence (GenBank:
      AY143693) was used as a template to design a primer pair to amplify partial duck
      HSP70 gene. Primers were subsequently designed with the duck HSP70 gene as a
      template to amplify the complete duck HSP70 sequence. 3. Twelve commercial
      Sanshui White ducklings were subjected to a heat stress experiment. Tissue
      samples were collected for RNA extraction and real-time PCR to analyse the
      expression mechanism of duck HSP70. 4. A DNA pool was constructed from three
      different species for single nucleotide polymorphism (SNP) screening. The
      genotypes of the identified SNPs were detected in 145 Sanshui White ducklings. 5.
      Duck HSP70 gene was identified and characterised (GenBank: EU678246) and shown to
      contain no introns. Fifteen variations were identified within the open reading
      frame. Quantitative real-time PCR results showed that the expression of duck
      HSP70 gene was tissue specific and the highest expression level was seen in
      pectoral muscle.

PMID- 24286501
TI  - Delimitation and description of the immature stages of a pollinating fig wasp,
      Ceratosolen solmsi marchali Mayr (Hymenoptera: Agaonidae).
AB  - The mutualism between fig trees and their wasp pollinators is a model system for
      many ecological and evolutionary studies. However, the immature stages of
      pollinating fig wasps have rarely been studied. We monitored developing fig wasps
      of known ages and performed a series of dissections at 24 h intervals to identify
      key developmental traits of Ceratosolen solmsi marchali Mayr (Hymenoptera:
      Agaonidae), a pollinator of Ficus hispida L. (Moraceae). We identified where in
      the Ficus ovary eggs were deposited and time to hatch. We were also able to
      identify the timing and key underlying characters of five larval instars, three
      sub-pupal stages, and a single prepupal stage. We provide detailed morphological
      descriptions for the key stages and report some behavioral observations of the
      wasps in the several developmental stages we recorded. Scanning electron
      microscope images were taken.

PMID- 24286503
TI  - Molecular cloning, expression and association study with reproductive traits of
      the duck LRP8 gene.
AB  - 1. Two splice variants of duck LRP8 were identified, one containing 8 ligand
      binding repeats (LRP8-1) and the other containing only 7 repeats (LRP8-2). The
      two transcripts share ~71-91% nucleic acid identity and ~65-94% amino acid
      identity with their counterparts in other species. A phylogenetic tree based on
      amino acid sequences shows that duck LRP8 proteins are closely related to those
      of chicken, turkey and zebra finch. 2. The semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR )analysis indicates that the two
      transcripts are expressed in all the examined tissues, and the LRP8-1 transcript
      is more highly expressed in hypothalamus, ovary and pituitary gland than in other
      detected tissues. 3. Six single nucleotide polymorphisms (SNPs) were identified
      in the coding region. Association analysis demonstrated that the c.528C > T
      genotypes were associated with egg production (EP) (EP210d, EP300d and EP360d),
      age at laying the first egg (AFE) and body weight at sexual maturity (BWSM). The
      c.1371A > G genotypes were associated with egg production (EP210d, EP300d and
      EP360d). 4. The haplotypes of c.528C > T and c.1371A > G were associated with EP
      (EP210d, EP300d and EP360d), yolk weight (YW), albumen weight (AW), egg weight
      (EW), BWSM and the first egg weight (FEW). 5. Duck LRP8 gene was associated with
      some reproductive traits and is an important candidate gene for the genetic
      selection of improved reproductive traits.

PMID- 24286504
TI  - Supplemental arginine administered in ovo or in the feed reduces the
      susceptibility of broilers to pulmonary hypertension syndrome.
AB  - 1. Two experiments were conducted to determine if in ovo and in-feed arginine
      (ARG) supplementation is effective in the prevention of pulmonary hypertension
      syndrome (PHS) in broiler chickens reared at high altitude. 2. In Experiment I, a
      total of 300 fertile eggs were divided into two equal groups. On d 5 of
      incubation, one group was injected with 0.5 ml of ARG (20 mg/ml) and the other
      remained untreated and served as controls. After hatching, male chicks (64
      chickens per treatment) were selected and given a commercial maize-soyabean meal
      diet up to 48 d of age. 3. In Experiment II, a total of 128 male broiler chickens
      (Ross 308) were randomly assigned to two treatments, a control group that were
      fed on a basal diet that met ARG requirements and the second was fed on the basal
      diet supplemented with 1.5 g ARG per kg of diet. 4. Cumulative mortality from
      ascites was recorded in both experiments. Results from Experiment I indicated
      that in ovo injection of ARG significantly decreased ascites mortality of
      broilers (18.8 vs. 43.8%). Results from Experiment II showed a similar effect so
      that ascites mortality in the group that were given Arg supplement was
      significantly lower than the control (28.1 vs. 43.8%). 

PMID- 24286506
TI  - Impact of surgical experience on recurrence and progression after transurethral
      resection of bladder tumour in non-muscle-invasive bladder cancer.
AB  - OBJECTIVE: This study aimed to evaluate the impact of experience in transurethral
      resection of bladder tumour (TURBT) on recurrence and progression in primary
      Ta/T1 urinary bladder cancer. MATERIAL AND METHODS: Clinical and pathological
      characteristics of patients with primary Ta/T1 urinary bladder cancer were
      recorded prospectively from 1992 to 2007 inclusive. Data on surgeons' experience
      were categorized as follows: experience by training status (residents or
      specialists); number of TURBTs performed by each surgeon during the registration
      period, with cut-off levels at more than 100, more than 150, more than 200,
      greater than the median and above the third quartile of surgical volume; and
      lifetime high-volume surgeons (>100 TURBTs). Hazard ratios (HRs) were estimated
      using Cox regression with 95% confidence intervals (CIs) in multivariate
      analyses. RESULTS: The analysis included 768 evaluable patients with a median
      follow-up of 60 months. Recurrence was observed in 478 patients (62%) and
      progression in 71 (9%). Surgery was performed by residents in 100 cases and
      specialists in 668, with recurrence in 75 (75%) and 403 (60%) patients, and
      progression in nine (9%) and 62 (9%), respectively. Surgery performed by
      specialists was significantly associated with a lower recurrence rate (HR = 0.68,
      95% CI 0.53-0.87) but not progression (HR = 0.76, 95% CI 0.37-1.56). Surgical
      volume had no significant impact on recurrence or progression in any of the
      analyses at the chosen cut-offs. CONCLUSIONS: Surgical experience
      (specialist/resident) was predictive for recurrence after TURBT for Ta/T1 bladder
      cancer. Training programmes, checklists and specialist-assisted surgery may
      shorten the learning curve and improve results.

PMID- 24286507
TI  - Caregiver-child mental health: a prospective study in conflict and refugee
      settings.
AB  - BACKGROUND: In humanitarian settings, family-level drivers of mental health are
      insufficiently documented; we examined the strength of caregiver-child
      associations with two-wave, family-level Afghan data. METHODS: We recruited a
      gender-balanced sample of 681 caregiver-child dyads (n = 1,362 respondents) using
      stratified random-sampling in government schools in Kabul (364 dyads) and refugee
      schools in Peshawar (317 dyads). One year after baseline, we re-interviewed 64%
      of Kabul and 31% of Peshawar cohorts (n = 331 dyads, 662 respondents), retaining
      fewer Peshawar families due to refugee repatriation. In multivariable analyses
      adjusted for baseline, we assessed the extent to which caregiver mental health
      (Self-Report Questionnaire, SRQ-20) was associated with child symptom scores of
      post-traumatic stress (Child Revised Impact of Events Scale, CRIES), depression
      (Depression Self-Rating Scale, DSRS), psychiatric difficulties, impact, and
      prosocial strength (Strength and Difficulties Questionnaire, SDQ). RESULTS:
      Caregiver mental health was prospectively associated with all eight measures of
      child mental health at follow-up, adjusted for baseline. For post-traumatic
      stress, caregiver mental health had a predictive impact comparable to the child
      experiencing one or two lifetime trauma events. For depression, caregiver mental
      health approached the predictive impact of female gender. Thus a one SD change in
      caregiver SRQ-20 was associated with a 1.04 point change on CRIES and a 0.65
      point change in DSRS. For multi-informant SDQ data, caregiver-child associations
      were strongest for caregiver ratings. For child-rated outcomes, associations were
      moderated by maternal literacy, a marker of family-level dynamics. Both adults
      and children identified domestic violence and quality of home life as independent
      risk and protective factors. CONCLUSIONS: In the context of violence and
      displacement, efforts to improve child mental health require a thoughtful
      consideration of the mental health cascade across generations and the cluster of
      adversities that impact family wellbeing. We identify culturally meaningful
      leverage points for building family-level resilience, relevant to the prevention
      and intervention agenda in global mental health.

PMID- 24286505
TI  - Single nucleotide polymorphisms in microRNA binding sites of oncogenes:
      implications in cancer and pharmacogenomics.
AB  - Cancer, a complex genetic disease involving uncontrolled cell proliferation, is
      caused by inactivation of tumor suppressor genes and activation of oncogenes. A
      vast majority of these cancer causing genes are known targets of microRNAs
      (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of
      messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms
      (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA
      interaction and can significantly affect gene expression. We hypothesized that
      3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post
      transcriptional regulation, resulting in overexpression of oncogenic proteins,
      tumor initiation, progression, and modulation of drug response in cancer
      patients. Therefore, we developed a systematic computational pipeline that
      integrates data from well-established databases, followed stringent selection
      criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA
      target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further,
      8 SNPs amidst them had the potential to determine therapeutic outcome in cancer
      patients. Functional annotation suggested that altogether these SNPs occur in
      proto-oncogenes enriched for kinase activities. We provide detailed in silico
      evidence for the functional effect of these candidate SNPs in various types of
      cancer.

PMID- 24286508
TI  - A novel cost-effective technology to convert sucrose and homocelluloses in sweet
      sorghum stalks into ethanol.
AB  - BACKGROUND: Sweet sorghum is regarded as a very promising energy crop for ethanol
      production because it not only supplies grain and sugar, but also offers
      lignocellulosic resource. Cost-competitive ethanol production requires
      bioconversion of all carbohydrates in stalks including of both sucrose and
      lignocellulose hydrolyzed into fermentable sugars. However, it is still a main
      challenge to reduce ethanol production cost and improve feasibility of industrial
      application. An integration of the different operations within the whole process
      is a potential solution. RESULTS: An integrated process combined advanced solid
      state fermentation technology (ASSF) and alkaline pretreatment was presented in
      this work. Soluble sugars in sweet sorghum stalks were firstly converted into
      ethanol by ASSF using crushed stalks directly. Then, the operation combining
      ethanol distillation and alkaline pretreatment was performed in one distillation
      reactor simultaneously. The corresponding investigation indicated that the
      addition of alkali did not affect the ethanol recovery. The effect of three
      alkalis, NaOH, KOH and Ca(OH)2 on pretreatment were investigated. The results
      indicated the delignification of lignocellulose by NaOH and KOH was more
      significant than that by Ca(OH)2, and the highest removal of xylan was caused by
      NaOH. Moreover, an optimized alkali loading of 10% (w/w DM) NaOH was determined.
      Under this favorable pretreatment condition, enzymatic hydrolysis of sweet
      sorghum bagasse following pretreatment was investigated. 92.0% of glucan and
      53.3% of xylan conversion were obtained at enzyme loading of 10 FPU/g glucan. The
      fermentation of hydrolyzed slurry was performed using an engineered stain,
      Zymomonas mobilis TSH-01. A mass balance of the overall process was calculated,
      and 91.9 kg was achieved from one tonne of fresh sweet sorghum stalk.
      CONCLUSIONS: A low energy-consumption integrated technology for ethanol
      production from sweet sorghum stalks was presented in this work. Energy
      consumption for raw materials preparation and pretreatment were reduced or
      avoided in our process. Based on this technology, the recalcitrance of
      lignocellulose was destructed via a cost-efficient process and all sugars in
      sweet sorghum stalks lignocellulose were hydrolysed into fermentable sugars.
      Bioconversion of fermentable sugars released from sweet sorghum bagasse into
      different products except ethanol, such as butanol, biogas, and chemicals was
      feasible to operate under low energy-consumption conditions.

PMID- 24286509
TI  - Tophus burden reduction with pegloticase: results from phase 3 randomized trials
      and open-label extension in patients with chronic gout refractory to conventional
      therapy.
AB  - INTRODUCTION: Two replicate randomized, placebo-controlled six-month trials
      (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase
      development program in patients with gout refractory to conventional therapy. In
      the RCTs, approximately 40% of patients treated with the approved dose saw
      complete response (CR) of at least one tophus. Here we describe the temporal
      course of tophus resolution, total tophus burden in patients with multiple tophi,
      tophus size at baseline, and the relationship between tophus response and urate
      lowering efficacy. METHODS: Baseline subcutaneous tophi were analyzed
      quantitatively using computer-assisted digital images in patients receiving
      pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in
      the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two
      ways. Overall tophus CR was the proportion of patients achieving a best response
      of CR (without any new/enlarging tophi) and target tophus complete response (TT
      CR) was the proportion of all tophi with CR. RESULTS: Among 212 patients
      randomized in the RCTs, 155 (73%) had >= 1 tophus and 547 visible tophi were
      recorded at baseline. Overall tophus CR was recorded in 45% of patients in the
      biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in
      the placebo group after six months of RCT therapy. TT-CR rates at six months were
      28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of
      sustained urate-lowering response to therapy (responders) were more likely than
      nonresponders to have an overall tophus CR at six months (54% vs 20%,
      respectively and 8% with placebo). CONCLUSIONS: Pegloticase reduced tophus burden
      in patients with refractory tophaceous gout, especially those achieving sustained
      urate-lowering. Complete resolution of tophi occurred in some patients by 13
      weeks and in others with longer-term therapy. TRIAL REGISTRATIONS: NCT00325195,
      NCT01356498.

PMID- 24286510
TI  - Trends in physician diagnosed gout and gout therapies in the US: results from the
      national ambulatory health care surveys 1993 to 2009.
AB  - INTRODUCTION: Gouty arthritis (gout) is primarily cared for in ambulatory care
      settings. Although the prevalence of gout in the US is thought to be increasing,
      there have been few data on this as well as temporal changes in gout medication
      use. METHODS: We analyzed annual visit and drug utilization data from national
      sample surveys of physician practices and hospital outpatient clinics in the US
      from 1993 to 2009. Gout diagnosis was recorded by individual physicians. RESULT:
      The frequency of visits for gout increased three-fold from 1993 through 2009;
      most of the increases were observed from 2003 onwards. The increase was only
      partly explained by changes in age and gender composition of the surveys over
      time. A concomitant increase in prescriptions for allopurinol and colchicine and
      decrease in prescriptions for anti-inflammatories was observed. Aspirin use, a
      putative risk factor for gout and gout flares, increased substantially over this
      period. Probenecid use was negligible. Frequency of systemic steroid use has not
      changed over time. CONCLUSIONS: The number of ambulatory visits for gout has
      increased almost three-fold in the first decade of the millennium coinciding with
      increases in physician and patient awareness. This increase was primarily due to
      visits among the elderly. Uricosuric use remained negligible whereas the uses of
      allopurinol and colchicine have increased rapidly. Use of traditional non
      steroidals has declined, possibly due to safety concerns whereas glucocorticoid
      use remains unchanged.

PMID- 24286511
TI  - Developing biographies: the experiences of children, young people and their
      parents of living with a long-term condition.
AB  - This article reports on data from a qualitative interview study that sought to
      understand the experiences, choices and actions of children and young people
      undergoing surgery for a long-term condition and that of their parents. Using the
      concept of biography the article examines how the biographies of children, young
      people and their parents can be influenced by surgery and the ongoing management
      of a long-term continence condition. This article challenges previous work that
      characterises the presence of a condition from birth as a continuous and normal
      part of the illness experiences of these patients. Although this may be the case
      in some instances, children, young people and their parents can experience
      diverse and changing experiences associated with ongoing condition management as
      well as surgery. Biographical continuity, enrichment and disruption are all
      relevant concepts for such patients living with a long-term continence condition.
      These can be influenced by their previous experiences of their condition, their
      expectations, and dynamics with parents, including changes associated with
      development and the increasing independence of young people.

PMID- 24286513
TI  - Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of
      apoptosis-related genes and pro-inflammatory cytokines.
AB  - OBJECTIVES: Cisplatin is an anti-neoplastic agent treatment with which causes
      many side effects including ototoxicity. The aim of this study was to investigate
      whether acetyl-L-carnitine would have protective effects on cisplatin-induced
      ototoxicity in vitro, and if present, to reveal roles of apoptotic gene
      expressions and pro-inflammatory cytokines. MATERIALS AND METHODS: House Ear
      Institute-Organ of Corti 1 cell line was used for this study. Apoptotic genes
      were evaluated with an apoptosis PCR array and pro-inflammatory cytokine levels
      were measured using ELISA. RESULTS: Apoptotic cell death reduced by around 22%
      with acetyl-L-carnitine-cisplatin treatment compared to cisplatin alone. Genes
      displaying increase in expression of apoptosis, related to cisplatin treatment,
      were Casp8, Bcl10, Bcl2, Bcl2l1, Bcl2l2, Bid, Naip1, Bnip3l, Card6, Pak7, Cd40,
      Trp 53inp1, Cideb and Cd70. The acetyl-L-carnitine-cisplatin combination caused
      reduced expression of genes Casp8, Fas, Casp1, Tnfrsf11b, Tnfrsf10b induced by
      cisplatin. Acetyl-L-carnitine-cisplatin also caused reduced levels of IL-6, IL
      1beta and TNF-alpha, pro-inflammatory cytokines, induced by cisplatin.
      CONCLUSION: Protective mechanisms of aceytl-L-carnitine against cisplatin induced
      apoptosis, mainly due to activation of anti-apoptotic Bcl family members' genes,
      and in an Akt-related gene expression dependent manner. This is the first study
      to indicate that acetyl-L-carnitine can be an effective agent against cisplatin
      ototoxicity in auditory cells, with induction of anti-apoptotic gene expression
      and attenuating levels of pro-inflammatory cytokines.

PMID- 24286512
TI  - Comparison of methods to identify aberrant expression patterns in individual
      patients: augmenting our toolkit for precision medicine.
AB  - BACKGROUND: Patient-specific aberrant expression patterns in conjunction with
      functional screening assays can guide elucidation of the cancer genome
      architecture and identification of therapeutic targets. Since most statistical
      methods for expression analysis are focused on differences between experimental
      groups, the performance of approaches for patient-specific expression analyses
      are currently less well characterized. A comparison of methods for the
      identification of genes that are dysregulated relative to a single sample in a
      given set of experimental samples, to our knowledge, has not been performed.
      METHODS: We systematically evaluated several methods including variations on the
      nearest neighbor based outlying degree method, as well as the Zscore and a robust
      variant for their suitability to detect patient-specific events. The methods were
      assessed using both simulations and expression data from a cohort of pediatric
      acute B lymphoblastic leukemia patients. RESULTS: We first assessed power and
      false discovery rates using simulations and found that even under optimal
      conditions, high effect sizes (>4 unit differences) were necessary to have
      acceptable power for any method (>0.9) though high false discovery rates (>0.1)
      were pervasive across simulation conditions. Next we introduced a technical
      factor into the simulation and found that performance was reduced for all methods
      and that using weights with the outlying degree could provide performance gains
      depending on the number of samples and genes affected by the technical factor. In
      our use case that highlights the integration of functional assays and aberrant
      expression in a patient cohort (the identification of gene dysregulation events
      associated with the targets from a siRNA screen), we demonstrated that both the
      outlying degree and the Zscore can successfully identify genes dysregulated in
      one patient sample. However, only the outlying degree can identify genes
      dysregulated across several patient samples. CONCLUSION: Our results show that
      outlying degree methods may be a useful alternative to the Zscore or Rscore in a
      personalized medicine context especially in small to medium sized (between 10 and
      50 samples) expression datasets with moderate to high sample-to-sample
      variability. From these results we provide guidelines for detection of aberrant
      expression in a precision medicine context.

PMID- 24286514
TI  - Letter to the editor: Comments on 'Cognitive remediation improves memory and
      psychosocial functioning in first-episode psychiatric out-patients'.

PMID- 24286515
TI  - Full-length genomic sequence of a new KIR3DL1*0150203 allele.
AB  - KIR3DL1*0150203 allele differs from KIR3DL1*0150201 at 3037G>A, 4115A>G, 6053G>C,
      8034A>G, 10723C>A, and 10747C>G. 

PMID- 24286517
TI  - Changes in the lifetime prevalence of suicidal feelings and thoughts among
      Norwegian doctors from 2000 to 2010: a longitudinal study based on national
      samples.
AB  - BACKGROUND: Thinking about suicide is an indicator of suicide risk. Suicide rates
      are higher among doctors than in the population. The main aims of this study are
      to describe the changes in the lifetime prevalence of suicidal feelings from 2000
      to 2010 and the possible predictors of serious suicidal thoughts in 2010 among
      Norwegian doctors. Differences in lifetime prevalence of suicidal feelings
      between Norwegian doctors in 2010 and German doctors in 2006 will be also
      described. METHODS: Longitudinal and cross-sectional study based on questionnaire
      data from 2000 and 2010, including approximately 1,600 Norwegian doctors. In
      Germany, cross-sectional study based on questionnaire data from 2006 among a
      sample of 3,295 doctors. The main outcome measures were the lifetime prevalence
      of suicidal feelings (felt life was not worth living, wished own death, had
      thoughts of taking own life). RESULTS: The prevalences in 2000 and 2010 of ever
      had feelings of life not worth living were 48 (44 to 52) % and 45 (41 to 49) %,
      of ever wished own death 27 (23 to 30) % and 23 (20 to 26) %, and of ever had
      thoughts of taking own life 29 (16 to 33) % and 24 (21 to 27) %. Paired t-tests
      among those who responded both in 2000 and 2010 show significant reductions for
      felt life not worth living (t = -3.4; p = 0.001), wished own death (t = -3.1; p =
      0.002) and had thoughts of taking own life (t = -3.5; p < 0.0001). In 2010,
      significant predictors of serious suicidal thoughts in a multivariate model were
      low subjective well-being (OR 0.68; 95% CI 0.52-0.90), poor or average self-rated
      health (2.36; 1.25-4.45) and high psychosocial work stress (1.92; 1.06-3.46),
      controlled for age, gender, speciality and job satisfaction. Norwegian doctors in
      2010 compared with their German counterparts in 2006 reported quite similar
      prevalences of suicidal feelings. CONCLUSIONS: Suicidal feelings among Norwegian
      doctors decreased from 2000 to 2010. Individual and work-related factors may to
      certain explain these findings. Compared with other professionals in Norway and
      doctors in Germany, Norwegian doctors showed no higher risk of suicidal thoughts.

PMID- 24286518
TI  - HIV service capacity: identifying current and future areas of clinical shortage.
AB  - Background The capacity of HIV services to meet the clinical needs of people
      living with HIV (PLHIV) has not been evaluated. Similarly, whether HIV services
      are positioned to respond to increases in patient demand outside metropolitan
      centres over the next decade is unknown. METHODS: A novel statistical methodology
      was used to estimate HIV clinical service capacity in Australia. A survey of HIV
      services was conducted. Geostatistical analysis was used to identify significant
      regions of clinical service undersupply relative to the estimated number of PLHIV
      in 2010 and 2020. RESULTS: In 2010, an estimated 2074 PLHIV (9.7% of all PLHIV)
      resided in regions more than 15km from a clinical service provider; 485 PLHIV
      (2.3% of all PLHIV) live >50km away. By 2020, this is estimated to rise to 3419
      and 807 (11.5% and 2.7% of estimated PLHIV) for 15km and 50km, respectively. To
      meet this demand, the establishment of new HIV services are required in the areas
      of greatest HIV clinical undersupply. In 2010, these are northern Sydney and
      western New South Wales, the Queensland mid-north coast and the outer suburbs of
      Melbourne. At the current estimated rate of increase in PLHIV, areas that will
      become critically undersupplied by 2020 include south-west Sydney, the outer
      suburbs of Brisbane and Western Australia. CONCLUSIONS: This study provides a
      quantitative assessment using modern statistical techniques to identify HIV
      clinical service gaps that is applicable in developed and nondeveloped settings.
      Training of new HIV clinicians should be directed towards undersupplied areas.

PMID- 24286516
TI  - The influence of cathelicidin LL37 in human anti-neutrophils cytoplasmic antibody
      (ANCA)-associated vasculitis.
AB  - INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) is characterised by the autoinflammation and necrosis of blood vessel
      walls. The renal involvement is commonly characterised by a pauci-immune
      crescentic glomerulonephritis (PiCGN) with a very rapid decline in renal
      function. Cathelicidin LL37, an endogenous antimicrobial peptide, has recently
      been implicated in the pathogenesis of autoimmune diseases. To assess whether
      serum LL37 reflects renal crescentic formation, we measured the serum levels of
      LL37 in AAV patients with and without crescentic glomerulonephritis (crescentic
      GN) as compared to healthy controls (HCs). We also analysed the correlation of
      the serum levels of LL37 and interferon-alpha (IFN-alpha) with the clinical
      characteristics of the patients. METHODS: The study population consisted of 85
      AAV patients and 51 HCs. In 40 ANCA-positive patients, a parallel analysis was
      performed, including the assessment of LL37 and IFN-alpha levels in the serum and
      renal biopsies. Of those studied, 15 AAV patients had biopsy-proven crescentic
      GN, and 25 AAV patients lacked crescent formation. The serum levels of
      cathelicidin LL37 and IFN-alpha were both measured by ELISA, and the clinical and
      serological parameters were assessed according to routine procedures.
      Immunofluorescence staining was performed on frozen sections of kidney needle
      biopsies from AAV patients with crescentic GN. RESULTS: The serum levels of LL37
      and IFN-alpha were significantly increased in AAV patients with crescentic GN
      compared to AAV patients without crescentic formation and HCs, and patients with
      high LL37 and IFN-alpha levels were more likely to be in the crescentic GN group.
      The LL37 levels were positively correlated with the IFN-alpha levels, and both
      LL37 and IFN-alpha levels showed a positive correlation with serum creatinine and
      no correlation with complement C3. The renal tissue of crescentic GN patients
      showed expression of LL37 and IFN-alpha at the Bowman's capsule and extracellular
      sites, suggesting the active release of LL37 and IFN-alpha. CONCLUSIONS:
      Significantly higher levels of LL-37 and IFN-alpha were observed in AAV patients,
      particularly those with crescentic formation, and LL37 and IFN-alpha were
      expressed in the renal tissue of patients with crescentic GN. These data suggest
      that serum levels of LL37 and IFN-alpha may reflect both local renal inflammation
      and systemic inflammation.

PMID- 24286519
TI  - CD56+ monocytes have a dysregulated cytokine response to lipopolysaccharide and
      accumulate in rheumatoid arthritis and immunosenescence.
AB  - INTRODUCTION: Peripheral blood monocytes are no longer regarded as a homogeneous
      cell population, but can be differentiated both phenotypically and functionally
      into various subpopulations. In rheumatoid arthritis, the subpopulation of
      CD14bright/CD16+ monocyte is expanded and prone towards generation of Th17 cells.
      CD56+ monocytes represent a different subpopulation, which is also expanded in
      conditions associated with autoimmunity like inflammatory bowel diseases. The aim
      of the study was the quantification and functional characterization of the CD56+
      monocyte subset in rheumatoid arthritis (RA). METHODS: Frequencies of peripheral
      blood monocyte subpopulations were analyzed by flow cytometry in 86 healthy
      controls and 75 RA patients. In 16 patients, anti-tumor necrosis factor (TNF)
      therapy was initiated, and the CD56+ monocyte frequency was monitored
      longitudinally. Lipopolysaccharide (LPS)-induced cytokine production of CD56+ and
      CD56- monocytes was determined by intracellular staining or cytokine secretion
      assays. RESULTS: In healthy individuals, 8.6% +/- 0.6 of the monocytes co
      expressed CD56, with the majority of CD56+ monocytes being CD14bright (7.9% +/-
      0.5), while only a minor population was CD14dim (0.7% +/- 0.1). We found a strong
      positive correlation between an individual's age and the frequency of CD56+
      monocytes. Upon stimulation with LPS, CD56+ monocytes became more frequently
      positive for TNF, IL-10 and IL-23 than CD56- monocytes. In addition, CD56+
      monocytes spontaneously produced more reactive oxygen intermediates than CD56-
      monocytes. In RA patients, the frequency of CD56+ monocytes was significantly
      higher than in healthy controls (12.2% +/- 0.9 vs. 7.9% +/- 0.5, p = 0.0002), and
      this difference most pronounced in RA patients below 40 years of age (11.1% +/-
      1.6 vs. 4.1% +/- 0.4, P < 0.0001). Treatment of the patients with an anti-TNF
      blocking agent significantly reduced CD56+ monocyte frequencies (baseline 12.4%
      vs. 24 weeks treatment 8.0%, P = 0.0429), and the magnitude of this decrease was
      found to correlate with the change in disease activity under the therapy.
      CONCLUSION: The CD14bright/CD56+ monocyte subset is expanded in aging individuals
      as well as in patients with RA. The pro-inflammatory production of cytokines and
      reactive oxygen species as well as the elimination of those cells in patients
      with a good response towards TNF inhibiting agents indicates a possible
      contribution of those monocytes in the inflammatory response in RA.

PMID- 24286521
TI  - Suicide risk assessment and risk formulation part II: Suicide risk formulation
      and the determination of levels of risk.
AB  - The suicide risk formulation (SRF) is dependent on the data gathered in the
      suicide risk assessment. The SRF assigns a level of suicide risk that is intended
      to inform decisions about triage, treatment, management, and preventive
      interventions. However, there is little published about how to stratify and
      formulate suicide risk, what are the criteria for assigning levels of risk, and
      how triage and treatment decisions are correlated with levels of risk. The
      salient clinical issues that define an SRF are reviewed and modeling is suggested
      for an SRF that might guide clinical researchers toward the refinement of an SRF
      process. 

PMID- 24286522
TI  - Is the Give Youth a Voice questionnaire an appropriate measure of teen-centred
      care in paediatric oncology: a Rasch measurement theory analysis.
AB  - BACKGROUND: Adolescents have their own views about the cancer care they receive
      and how they feel they are treated, but their opinions are rarely solicited.
      OBJECTIVE: To determine whether the 56-item Give Youth a Voice (GYV-56), its
      subscales and its 20-item short-form, are clinically meaningful and
      psychometrically sound instruments that can be used to measure teen-centred care
      (TCC) in paediatric oncology. DESIGN: Qualitative interviews and a questionnaire
      survey. SETTING AND PARTICIPANTS: Qualitative interviews with 38 childhood cancer
      survivors. GYV-56 data collected from 200 paediatric cancer patients and
      survivors. MAIN OUTCOME MEASURE: The GYV-56, which measures the following four
      aspects of service delivery: Supportive and respectful relationships; Information
      sharing and communication; Supporting independence; and Teen-centred services.
      RESULTS: Qualitative data provided broad support for the TCC conceptual framework
      and GYV-56 items. After post-hoc reduction of the response options from 7 to 3
      (to correct for disordered thresholds), fit to the Rasch model was good, most
      items showed acceptable fit residuals and chi-square P-values, scale reliability
      were supported and item locations defined a continuum for TCC that was well
      targeted to the sample. By calibrating the items for each subscale and the short
      form to the full scale, the scores obtained on each measure are directly
      comparable. CONCLUSION: Our study found initial support for use of the GYV with a
      reduced response option format for examining TCC in the adolescent oncology
      patients. in this paediatric population. Further research using the GYV is needed
      to elaborate upon our findings.

PMID- 24286523
TI  - Better recovery of kidney function in patients with de novo chronic kidney
      disease after partial nephrectomy compared with those with pre-existing chronic
      kidney disease.
AB  - We compared kidney functional recovery between patients with pre-existing chronic
      kidney disease, those with de novo chronic kidney disease and those with normal
      kidney function, after partial nephrectomy. A total of 311 patients who underwent
      partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan,
      between January 2004 and July 2011 with sufficient kidney functional data
      participated in the study. Patients with pre-existing chronic kidney disease
      (group1: 78 patients) were defined as those with estimated glomerular filtration
      rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo
      chronic kidney disease (group 2: 49) were defined as those with estimated
      glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed
      estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial
      nephrectomy. Normal patients (group 3: 184) were defined as those with estimated
      glomerular filtration rate over 60 mL/min/m(2) both before and after partial
      nephrectomy. Group 1 was associated with older age and higher comorbidity,
      including hypertension and diabetes mellitus, compared with other groups.
      R.E.N.A.L. score was not significantly different between the groups. Although the
      percent change of estimated glomerular filtration rate between the preoperative
      period and 3 months after partial nephrectomy in group 2 was significantly
      decreased compared with that in other groups (group 1: -6.8%, group 2: -18%,
      group 3: -7.3%), the renal functional recovery between 3 and 12 months after
      partial nephrectomy in group 2 was better than that in other groups (group 1: 
      0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney
      disease had better kidney functional recovery than the other two groups, which
      might suggest that they were surgically assaulted and developed chronic kidney
      disease in the early postoperative period, and were essentially different from
      those with pre-existing chronic kidney disease.

PMID- 24286524
TI  - Tracking the cellulolytic activity of Clostridium thermocellum biofilms.
AB  - BACKGROUND: Microbial cellulose conversion by Clostridium thermocellum 27405
      occurs predominantly through the activity of substrate-adherent bacteria
      organized in thin, primarily single cell-layered biofilms. The importance of
      cellulosic surface exposure to microbial hydrolysis has received little attention
      despite its implied impact on conversion kinetics. RESULTS: We showed the spatial
      heterogeneity of fiber distribution in pure cellulosic sheets, which made direct
      measurements of biofilm colonization and surface penetration impossible.
      Therefore, we utilized on-line measurements of carbon dioxide (CO2) production in
      continuous-flow reactors, in conjunction with confocal imaging, to observe
      patterns of biofilm invasion and to indirectly estimate microbial accessibility
      to the substrate's surface and the resulting limitations on conversion kinetics.
      A strong positive correlation was found between cellulose consumption and CO2
      production (R2 = 0.996) and between surface area and maximum biofilm activity (R2
      = 0.981). We observed an initial biofilm development rate (0.46 h-1, 0.34 h-1 and
      0.33 h-1) on Whatman sheets (#1, #598 and #3, respectively) that stabilized when
      the accessible surface was maximally colonized. The results suggest that
      cellulose conversion kinetics is initially subject to a microbial limitation
      period where the substrate is in excess, followed by a substrate limitation
      period where cellular mass, in the form of biofilms, is not limiting. Accessible
      surface area acts as an important determinant of the respective lengths of these
      two distinct periods. At end-point fermentation, all sheets were digested
      predominantly under substrate accessibility limitations (e.g., up to 81% of total
      CO2 production for Whatman #1). Integration of CO2 production rates over time
      showed Whatman #3 underwent the fastest conversion efficiency under microbial
      limitation, suggestive of best biofilm penetration, while Whatman #1 exhibited
      the least recalcitrance and the faster degradation during the substrate
      limitation period. CONCLUSION: The results showed that the specific biofilm
      development rate of cellulolytic bacteria such as C. thermocellum has a notable
      effect on overall reactor kinetics during the period of microbial limitation,
      when ca. 20% of cellulose conversion occurs. The study further demonstrated the
      utility of on-line CO2 measurements as a method to assess biofilm development and
      substrate digestibility pertaining to microbial solubilization of cellulose,
      which is relevant when considering feedstock pre-treatment options.

PMID- 24286525
TI  - Use of an open-source Geographic Information System-based method for topographic
      analysis of nodular cutaneous lesions in dogs.

PMID- 24286526
TI  - Reconstructing apology: David Cameron's Bloody Sunday apology in the press.
AB  - While there is an acknowledgement in apology research that political apologies
      are highly mediated, the process of mediation itself has lacked scrutiny. This
      article suggests that the idea of reconstruction helps to understand how
      apologies are mediated and evaluated. David Cameron's apology for Bloody Sunday
      is examined to see how he constructs four aspects of apology: social actors,
      consequences, categorization, and reasons. The reconstruction of those aspects by
      British, Unionist, and Nationalist press along with reconstructions made by
      soldiers in an online forum are considered. Data analysis was informed by
      thematic analysis and discourse analysis which helped to explore key aspects of
      reconstruction and how elements of Cameron's apology are altered in subsequent
      mediated forms of the apology. These mediated reconstructions of the apology
      allowed their authors to evaluate the apology in different ways. Thus, in this
      article, it is suggested that the evaluation of the apology by different groups
      is preceded by a reconstruction of it in accordance with rhetorical goals. This
      illuminates the process of mediation and helps to understand divergent responses
      to political apologies. 

PMID- 24286520
TI  - Annual research review: The neurobehavioral development of multiple memory
      systems--implications for childhood and adolescent psychiatric disorders.
AB  - Extensive evidence indicates that mammalian memory is organized into multiple
      brains systems, including a 'cognitive' memory system that depends on the
      hippocampus and a stimulus-response 'habit' memory system that depends on the
      dorsolateral striatum. Dorsal striatal-dependent habit memory may in part
      influence the development and expression of some human psychopathologies,
      particularly those characterized by strong habit-like behavioral features. The
      present review considers this hypothesis as it pertains to psychopathologies that
      typically emerge during childhood and adolescence. These disorders include
      Tourette syndrome, attention-deficit/hyperactivity disorder, obsessive-compulsive
      disorder, eating disorders, and autism spectrum disorders. Human and nonhuman
      animal research shows that the typical development of memory systems comprises
      the early maturation of striatal-dependent habit memory and the relatively late
      maturation of hippocampal-dependent cognitive memory. We speculate that the
      differing rates of development of these memory systems may in part contribute to
      the early emergence of habit-like symptoms in childhood and adolescence. In
      addition, abnormalities in hippocampal and striatal brain regions have been
      observed consistently in youth with these disorders, suggesting that the aberrant
      development of memory systems may also contribute to the emergence of habit-like
      symptoms as core pathological features of these illnesses. Considering these
      disorders within the context of multiple memory systems may help elucidate the
      pathogenesis of habit-like symptoms in childhood and adolescence, and lead to
      novel treatments that lessen the habit-like behavioral features of these
      disorders. 

PMID- 24286527
TI  - A severe case of Hirayama disease successfully treated by anterior cervical
      fusion.
AB  - Hirayama disease, or juvenile amyotrophy of distal upper extremity, is a benign,
      self-limiting cervical myelopathy consisting of selective unilateral weakness of
      the hand and forearm. The weakness slowly progresses until spontaneous arrest
      occurs within 5 years of onset. The condition predominantly affects Asian males
      and is thought to be secondary to spinal cord compression during neck flexion,
      because of a forward displacement of the posterior dural sac. The authors present
      what is to their knowledge the first reported case of a Caucasian male with a
      severe form of Hirayama disease, suffering from weakness of the leg as well as
      the forearm. An abnormal range of cervical flexion was observed at the C5-6
      level. The patient was successfully treated by anterior cervical discectomy and
      fusion. 

PMID- 24286528
TI  - Biomechanical analysis of an interspinous fusion device as a stand-alone and as
      supplemental fixation to posterior expandable interbody cages in the lumbar
      spine.
AB  - OBJECT: In this paper the authors evaluate through in vitro biomechanical testing
      the performance of an interspinous fusion device as a stand-alone device, after
      lumbar decompression surgery, and as supplemental fixation to expandable cages in
      a posterior lumbar interbody fusion (PLIF) construct. METHODS: Nine L3-4 human
      cadaveric spines were biomechanically tested under the following conditions: 1)
      intact/control; 2) L3-4 left hemilaminotomy with partial discectomy (injury); 3)
      interspinous spacer (ISS); 4) bilateral pedicle screw system (BPSS); 5) bilateral
      hemilaminectomy, discectomy, and expandable posterior interbody cages with ISS
      (PLIF-ISS); and 6) PLIF-BPSS. Each test consisted of 100 N of axial preload with
      +/- 7.5 Nm of torque in flexion-extension, right/left lateral bending, and
      right/left axial rotation. Significant changes in range of motion (ROM), neutral
      zone stiffness (NZS), elastic zone stiffness (EZS), and energy loss (EL) were
      explored among conditions using nonparametric Friedman test and Wilcoxon signed
      rank comparisons (p <= 0.05). RESULTS: The injury increased ROM in flexion (p =
      0.01), left bending (p = 0.03), and right/left rotation (p < 0.01) and also
      decreased NZS in flexion (p = 0.01) and extension (p < 0.01). Both the ISS and
      BPSS reduced flexion-extension ROM and increased flexion-extension stiffness (NZS
      and EZS) with respect to the injury and intact conditions (p < 0.05), but the ISS
      condition provided greater resistance than BPSS in extension for ROM, NZS, and
      EZS (p < 0.01). The BPSS increased the rigidity (ROM, NZS, and EZS) of the intact
      model in lateral bending and axial rotation (p <= 0.01), except in EZS for left
      rotation (p = 0.23, Friedman test). The incorporation of posterior cages
      marginally increased (p = 0.05) the EZS of the BPSS construct in flexion but
      these interbody devices provided significant stability to the ISS construct in
      lateral bending and axial rotation for ROM (p = 0.02), in lateral bending for NZS
      (p = 0.02), and in flexion/axial rotation for EZS (p <= 0.03); however, both PLIF
      constructs demonstrated equivalent ROM and stiffness (p >= 0.16), except in
      lateral bending where the PLIF-BPSS was more stable (p = 0.02). In terms of EL,
      the injury increased EL in flexion-extension (p = 0.02), the ISS increased EL for
      lateral bending and axial rotation (p <= 0.03), and the BPSS decreased EL in
      lateral bending (p = 0.02), with respect to the intact condition. The PLIF-ISS
      decreased lateral bending EL with respect to the ISS condition (p = 0.02), but
      not enough to be smaller or, at least, equivalent, to that of the PLIF-BPSS
      construct (p = 0.02). CONCLUSIONS: The ISS may be a suitable device to provide
      immediate flexion-extension balance after a unilateral laminotomy, but the BPSS
      provides greater immediate stability in lateral bending and axial rotation
      motions. Both PLIF constructs performed equivalently in flexion-extension and
      axial rotation, but the PLIF-BPSS construct is more resistant to lateral bending
      motions. Further biomechanical and clinical evidence is required to strongly
      support the recommendation of a stand-alone interspinous fusion device or as
      supplemental fixation to expandable posterior interbody cages.

PMID- 24286529
TI  - Traumatic, high-cervical, coronal-plane spondyloptosis with unilateral vertebral
      artery occlusion: treatment using a prophylactic arterial bypass graft, open
      reduction, and instrumented segmental fusion.
AB  - The authors present a case of traumatic, complete, high cervical spine injury in
      a patient with gradual worsening deformity and neck pain while in rigid cervical
      collar immobilization, ultimately resulting in coronal-plane spondyloptosis. Due
      to the extent of lateral displacement of the spinal elements, preoperative
      evaluation included catheter angiography, which revealed complete right vertebral
      artery (VA) occlusion. A prophylactic arterial bypass graft from the right
      occipital artery to the extradural right VA was fashioned to augment posterior
      circulation blood supply prior to reduction and circumferential instrumented
      fusion. Following surgery, the patient was able to participate in an aggressive
      rehabilitation program allowing early mobilization, and he ceased to be
      ventilator-dependent following implantation of a diaphragmatic pacer. The authors
      review factors leading to progression of this type of injury and suggest
      technical pearls as well as highlight specific management pitfalls, including
      operative risks. 

PMID- 24286530
TI  - Discharge dispositions, complications, and costs of hospitalization in spinal
      cord tumor surgery: analysis of data from the United States Nationwide Inpatient
      Sample, 2003-2010.
AB  - OBJECT: The aim of this study was to analyze the incidence of adverse outcomes
      and inpatient mortality following resection of intramedullary spinal cord tumors
      by using the US Nationwide Inpatient Sample (NIS) database. The overall
      complication rate, length of the hospital stay, and the total cost of
      hospitalization were also analyzed from the database. METHODS: This is a
      retrospective cohort study conducted using the NIS data from 2003 to 2010.
      Various patient-related (demographic categories, complications, comorbidities,
      and median household income) and hospital-related variables (number of beds,
      high/low case volume, rural/urban location, region, ownership, and teaching
      status) were analyzed from the database. The adverse discharge disposition, in
      hospital mortality, and the higher cost of hospitalization were taken as the
      dependent variables. RESULTS: A total of 15,545 admissions were identified from
      the NIS database. The mean patient age was 44.84 +/- 19.49 years (mean +/- SD),
      and 7938 (52%) of the patients were male. Regarding discharge disposition, 64.1%
      (n = 9917) of the patients were discharged to home or self-care, and the overall
      in-hospital mortality rate was 0.46% (n = 71). The mean total charges for
      hospitalization increased from $45,452.24 in 2003 to $76,698.96 in 2010. Elderly
      patients, female sex, black race, and lower income based on ZIP code were the
      independent predictors of other than routine (OTR) disposition (p < 0.001).
      Private insurance showed a protective effect against OTR disposition. Patients
      with a higher comorbidity index (OR 1.908, 95% CI 1.733-2.101; p < 0.001) and
      with complications (OR 2.214, 95% CI 1.768-2.772; p < 0.001) were more likely to
      have an adverse discharge disposition. Hospitals with a larger number of beds and
      those in the Northeast region were independent predictors of the OTR discharge
      disposition (p < 0.001). Admissions on weekends and nonelective admission had
      significant influence on the disposition (p < 0.001). Weekend and nonelective
      admissions were found to be independent predictors of inpatient mortality and the
      higher cost incurred to the hospitals (p < 0.001). High-volume and large
      hospitals, West region, and teaching hospitals were also the predictors of higher
      cost incurred to the hospitals (p < 0.001). The following variables (young
      patients, higher median household income, nonprivate insurance, presence of
      complications, and a higher comorbidity index) were significantly correlated with
      higher hospital charges (p < 0.001), whereas the variables young patients,
      nonprivate insurance, higher median household income, and higher comorbidity
      index independently predicted for inpatient mortality (p < 0.001). CONCLUSIONS:
      The independent predictors of adverse discharge disposition were as follows:
      elderly patients, female sex, black race, lower median household income,
      nonprivate insurance, higher comorbidity index, presence of complications, larger
      hospital size, Northeast region, and weekend and nonelective admissions. The
      predictors of higher cost incurred to the hospitals were as follows: young
      patients, higher median household income, nonprivate insurance, presence of
      complications, higher comorbidity index, hospitals with high volume and a large
      number of beds, West region, teaching hospitals, and weekend and nonelective
      admissions.

PMID- 24286531
TI  - Prospective assessment of concomitant lumbar and chronic subdural hematoma: is
      migration from the intracranial space involved in their manifestation?
AB  - OBJECT: Spinal subdural hematomas (SDHs) are rare and some are concomitant with
      intracranial SDH. Their pathogenesis and etiology remain to be elucidated
      although their migration from the intracranial space has been suggested. The
      authors postulated that if migration plays a major role, patients with
      intracranial SDH may harbor asymptomatic lumbar SDH. The authors performed a
      prospective study on the incidence of spinal SDH in patients with intracranial
      SDH to determine whether migration is a key factor in their concomitance.
      METHODS: The authors evaluated lumbar MR images obtained in 168 patients (125
      males, 43 females, mean age 75.6 years) with intracranial chronic SDH to identify
      cases of concomitant lumbar SDH. In all cases, the lumbar MRI studies were
      performed within the 1st week after surgical irrigation of the intracranial SDH.
      RESULTS: Of the 168 patients, 2 (1.2%) harbored a concomitant lumbar SDH; both
      had a history of trauma to both the head and the hip and/or lumbar area. One was
      an 83-year-old man with prostate cancer and myelodysplastic syndrome who suffered
      trauma to his head and lumbar area in a fall from his bed. The other was a 70
      year-old man who had hit his head and lumbar area in a fall. Neither patient
      manifested neurological deficits and their hematomas disappeared under
      observation. None of the patients with concomitant lumbar SDH had sustained head
      trauma only, indicating that trauma to the hip or lumbar region is significantly
      related to the concomitance of SDH (p < 0.05). CONCLUSIONS: As the incidence of
      concomitant lumbar and intracranial chronic SDH is rare and both patients in this
      study had sustained a direct impact to the head and hips, the authors suggest
      that the major mechanism underlying their concomitant SDH was double trauma.
      Another possible explanation is hemorrhagic diathesis and low CSF syndrome.

PMID- 24286532
TI  - Mouse infection and pathogenesis by Trypanosoma brucei motility mutants.
AB  - The flagellum of Trypanosoma brucei is an essential and multifunctional organelle
      that drives parasite motility and is receiving increased attention as a potential
      drug target. In the mammalian host, parasite motility is suspected to contribute
      to infection and disease pathogenesis. However, it has not been possible to test
      this hypothesis owing to lack of motility mutants that are viable in the
      bloodstream life cycle stage that infects the mammalian host. We recently
      identified a bloodstream-form motility mutant in 427-derived T. brucei in which
      point mutations in the LC1 dynein subunit disrupt propulsive motility but do not
      affect viability. These mutants have an actively beating flagellum, but cannot
      translocate. Here we demonstrate that the LC1 point mutant fails to show enhanced
      cell motility upon increasing viscosity of the surrounding medium, which is a
      hallmark of wild type T. brucei, thus indicating that motility of the mutant is
      fundamentally altered compared with wild type cells. We next used the LC1 point
      mutant to assess the influence of trypanosome motility on infection in mice.
      Wesurprisingly found that disrupting parasite motility has no discernible effect
      on T. brucei bloodstream infection. Infection time-course, maximum parasitaemia,
      number of waves of parasitaemia, clinical features and disease outcome are
      indistinguishable between motility mutant and control parasites. Our studies
      provide an important step toward understanding the contribution of parasite
      motility to infection and a foundation for future investigations of T. brucei
      interaction with the mammalian host.

PMID- 24286533
TI  - Outcomes of abdominal wall reservoir placement in inflatable penile prosthesis
      implantation: a safe and efficacious alternative to the space of Retzius.
AB  - INTRODUCTION: Inflatable penile prosthesis (IPP) surgery is a successful
      therapeutic option for men with erectile dysfunction. Traditional placement of
      the reservoir in the retropubic space of Retzius is associated with the rare
      occurrence of significant complications including bladder, bowel, and vascular
      injury. An alternative site, posterior to the abdominal wall musculature, has
      been identified as a potentially safer location for reservoir placement. AIMS:
      The aim of this study was to describe our technique of abdominal reservoir
      placement during infrapubic IPP surgery and present our outcomes data. METHODS:
      We retrospectively reviewed our experience with abdominal reservoir placement
      during virgin IPP cases. Reservoirs placed anterior and posterior to
      transversalis fascia were analyzed separately. MAIN OUTCOME MEASURE: The main
      outcome measures was assessment of reservoir-related complications including
      palpable reservoir, reservoir herniation, and injuries to bowel, bladder, or
      major blood vessels. RESULTS: There were no injuries to bowel or major blood
      vessels with abdominal reservoir placement posterior or anterior to the
      transversalis fascia in properly segregated patients. CONCLUSION: Abdominal
      reservoir placement is a safe and simple surgical method that can be recommended
      for most men undergoing IPP placement. Men with a history of pelvic surgery can
      have the reservoir placed between the rectus abdominis musculature and
      transversalis fascia, while other men can have the reservoir placed between
      transversalis fascia and peritoneum in order to avoid a palpable reservoir. By
      applying this protocol, the catastrophic injuries that occur rarely with
      retropubic reservoir placement can be reliably avoided.

PMID- 24286534
TI  - Efficacy of zinc-carnosine chelate compound, Polaprezinc, enemas in patients with
      ulcerative colitis.
AB  - OBJECTIVES: Ulcerative colitis (UC) is a chronic, relapsing and remitting
      intestinal inflammatory disorder. Zinc is known to be efficacious for the repair
      of damaged tissue and has been shown to protect against gastric ulceration. This
      study focused on Polaprezinc (PZ), N-(3-aminopropionyl)-L-histidinato zinc, which
      accelerates ulcer healing through actions such as prostaglandin-independent
      cytoprotection and antioxidative activity. METHODS: In this randomized, placebo
      controlled, investigator-blinded trial, 28 patients with active UC at The Jikei
      University Hospital were randomly divided into two groups: one treated with a 150
      mg PZ enema (n = 18) and the other not treated with a PZ enema (n = 10). All
      patients received usual induction therapy. Clinical symptoms, endoscopic findings
      and histological findings were evaluated at entry and one week later. RESULTS: In
      the PZ group, modified Matts' endoscopic scores were significantly improved after
      treatment compared to baseline in the rectum (p = 0.004), sigmoid colon (p =
      0.03) and descending colon (p = 0.04). In the non-PZ group, scores were not
      significantly improved in the rectum (p = 0.14) and descending colon (p = 0.34),
      but were improved in the sigmoid colon (p = 0.04). In the PZ group, the Mayo
      scores at baseline and at Day 8 were 9.1 +/- 1.6 and 5.8 +/- 2.7 (p = 0.00004),
      respectively, and in the placebo group, the scores were 8.9 +/- 1.7 and 7.4 +/-
      2.1 (p = 0.009), respectively. Clinical response or remission was significantly
      better in the PZ group (71%) than in the placebo group (10%). CONCLUSIONS: A zinc
      carnosine chelate compound, PZ, enema may become a useful new add-on treatment to
      accelerate mucosal healing in UC.

PMID- 24286535
TI  - Natural killer cells and natural killer T cells in Lyme arthritis.
AB  - INTRODUCTION: Natural killer (NK) and natural killer T (NKT) cells provide a
      first line of defense against infection. However, these cells have not yet been
      examined in patients with Lyme arthritis, a late disease manifestation. Lyme
      arthritis usually resolves with antibiotic treatment. However, some patients have
      persistent arthritis after spirochetal killing, which may result from excessive
      inflammation, immune dysregulation and infection-induced autoimmunity. METHODS:
      We determined the frequencies and phenotypes of NK cells and invariant NKT (iNKT)
      cells in paired peripheral blood (PB) and synovial fluid (SF) samples from eight
      patients with antibiotic-responsive arthritis and fifteen patients with
      antibiotic-refractory arthritis using flow cytometry and cytokine analyses.
      RESULTS: In antibiotic-responsive patients, who were seen during active
      infection, high frequencies of CD56bright NK cells were found in SF, the
      inflammatory site, compared with PB (P <0.001); at both sites, a high percentage
      of cells expressed the activation receptor NKG2D and the chaperone CD94, a low
      percentage expressed inhibitory killer immunoglobulin-like receptors (KIR), and a
      high percentage produced IFN-gamma. In antibiotic-refractory patients, who were
      usually evaluated near the conclusion of antibiotics when few if any live
      spirochetes remained, the phenotype of CD56bright cells in SF was similar to that
      in patients with antibiotic-responsive arthritis, but the frequency of these
      cells was significantly less (P = 0.05), and the frequencies of CD56dim NK cells
      tended to be higher. However, unlike typical NKdim cells, these cells produced
      large amounts of IFN-gamma, suggesting that they were not serving a cytotoxic
      function. Lastly, iNKT cell frequencies in the SF of antibiotic-responsive
      patients were significantly greater compared with that of antibiotic-refractory
      patients where these cells were often absent (P = 0.003). CONCLUSIONS: In
      patients with antibiotic-responsive arthritis, the high percentage of activated,
      IFN-gamma-producing CD56bright NK cells in SF and the presence of iNKT cells
      suggest that these cells still have a role in spirochetal killing late in the
      illness. In patients with antibiotic-refractory arthritis, the frequencies of IFN
      gamma-producing CD56bright and CD56dim NK cells remained high in SF, even after
      spirochetal killing, suggesting that these cells contribute to excessive
      inflammation and immune dysregulation in joints, and iNKT cells, which may have
      immunomodulatory effects, were often absent.

PMID- 24286536
TI  - Efficiency of whole genome amplification of single circulating tumor cells
      enriched by CellSearch and sorted by FACS.
AB  - BACKGROUND: Tumor cells in the blood of patients with metastatic carcinomas are
      associated with poor survival. Knowledge of the cells' genetic make-up can help
      to guide targeted therapy. We evaluated the efficiency and quality of isolation
      and amplification of DNA from single circulating tumor cells (CTC). METHODS: The
      efficiency of the procedure was determined by spiking blood with SKBR-3 cells,
      enrichment with the CellSearch system, followed by single cell sorting by
      fluorescence-activated cell sorting (FACS) and whole genome amplification. A
      selection of single cell DNA from fixed and unfixed SKBR-3 cells was exome
      sequenced and the DNA quality analyzed. Single CTC from patients with lung cancer
      were used to demonstrate the potential of single CTC molecular characterization.
      RESULTS: The overall efficiency of the procedure from spiked cell to amplified
      DNA was approximately 20%. Losses attributed to the CellSearch system were around
      20%, transfer to FACS around 25%, sorting around 5% and DNA amplification around
      25%. Exome sequencing revealed that the quality of the DNA was affected by the
      fixation of the cells, amplification, and the low starting quantity of DNA. A
      single fixed cell had an average coverage at 20* depth of 30% when sequencing to
      an average of 40* depth, whereas a single unfixed cell had 45% coverage.
      GenomiPhi-amplified genomic DNA had a coverage of 72% versus a coverage of 87% of
      genomic DNA. Twenty-one percent of the CTC from patients with lung cancer
      identified by the CellSearch system could be isolated individually and amplified.
      CONCLUSIONS: CTC enriched by the CellSearch system were sorted by FACS, and DNA
      retrieved and amplified with an overall efficiency of 20%. Analysis of the
      sequencing data showed that this DNA could be used for variant calling, but not
      for quantitative measurements such as copy number detection. Close to 55% of the
      exome of single SKBR-3 cells were successfully sequenced to 20* depth making it
      possible to call 72% of the variants. The overall coverage was reduced to 30% at
      20* depth, making it possible to call 56% of the variants in CellSave-fixed
      cells.

PMID- 24286537
TI  - Exploring causal pathways of child behavior and maternal mental health in
      families with a child with congenital heart disease: a longitudinal study.
AB  - BACKGROUND: A congenital heart defect (CHD) can increase the risk of mental
      health problems in affected children and their parents. The extent to which risk
      factors for these problems are shared in families or are specific to the
      individual family member is unclear. METHOD: Prospective data from the Norwegian
      Mother and Child Cohort Study (MoBa; n = 93,009) were linked with a nationwide
      CHD registry, and 408 children with CHD were identified. Mothers' reports on
      child internalizing problems and their own distress were assessed by
      questionnaires at child ages 6, 18 and 36 months. A structural model was applied
      to distinguish between familial (shared) factors and individual-specific factors
      for mental health problems. RESULTS: CHD was a substantial risk factor for
      problems in children and their mothers at all time points. CHD contributed on
      average 31% and 39% to the variance in children's and mothers' problems
      respectively. Both shared familial and individual-specific factors unique to CHD
      families contributed to risk for mental health problems. Whereas individual
      specific risk factors contributed to the stability of problems in mothers, the
      effect of these factors lasted only a short time in children. Mutual influences
      over time were found between the mother's and the child's mental health at 18 and
      36 months. CONCLUSIONS: The burden of CHD in a child is shared between family
      members but is also specific to the individual. This study points to a need for
      both an individual and a family-based approach to provide psychological support
      to children with CHD and their parents.

PMID- 24286538
TI  - Cancer incidence and radiation therapy in Mozambique - a comparative study to
      Sweden.

PMID- 24286539
TI  - Image guided therapy - do we get the picture?

PMID- 24286540
TI  - Very different performance of the power Doppler modalities of several ultrasound
      machines ascertained by a microvessel flow phantom.
AB  - INTRODUCTION: In many patients with rheumatoid arthritis (RA) subclinical disease
      activity can be detected with ultrasound (US), especially using power Doppler US
      (PDUS). However, PDUS may be highly dependent on the type of machine. This could
      create problems both in clinical trials and in daily clinical practice. To
      clarify how the PDUS signal differs between machines we created a microvessel
      flow phantom. METHODS: The flow phantom contained three microvessels (150, 1000,
      2000 microns). A syringe pump was used to generate flows. Five US machines were
      used. Settings were optimised to assess the lowest detectable flow for each US
      machine. RESULTS: The minimal detectable flow velocities showed very large
      differences between the machines. Only two of the machines may be able to detect
      the very low flows in the capillaries of inflamed joints. There was no clear
      relation with price. One of the lower-end machines actually performed best in all
      three vessel sizes. CONCLUSIONS: We created a flow phantom to test the
      sensitivity of US machines to very low flows in small vessels. The sensitivity of
      the power Doppler modalities of 5 different machines was very different. The
      differences found between the machines are probably caused by fundamental
      differences in processing of the PD signal or internal settings inaccessible to
      users. Machines considered for PDUS assessment of RA patients should be tested
      using a flow phantom similar to ours. Within studies, only a single machine type
      should be used.

PMID- 24286541
TI  - HLA-A*11:119:02, a variant of HLA-A*11, found in a Taiwanese unrelated bone
      marrow stem cell donor.
AB  - Two nucleotide replacements in codons 127 and 139 of the human leukocyte antigen
      HLA-A*11:01:01 results in a novel allele, HLA-A*11:119:02. 

PMID- 24286542
TI  - Effect of ear acupressure on acute postpartum perineal pain: a randomised
      controlled study.
AB  - AIMS AND OBJECTIVES: To explore the effect of ear acupressure in relieving
      perineal pain in women during the first 48 hours after delivery. BACKGROUND:
      Perineal pain is a common problem during postpartum, and different treatment
      modalities have been used for relief. Ear acupressure has been reported to have
      possible benefit on relieving acute postpartum perineal pain. DESIGN: This study
      was designed as a prospective, randomised controlled trial. METHODS: Chinese
      women with a singleton vertex foetus at the gestation of 37 weeks or above were
      recruited. One hundred and twenty six and 130 women were randomised into the
      intervention and control groups, respectively. Women in the intervention group
      received application of tapes and seeds on four designated acupressure points on
      both ears, while women in the control group received tapes on four irrelevant
      points. Both groups were instructed to stimulate the points in a similar fashion.
      Pain perception was assessed by the Verbal Descriptive Pain Scale and the Visual
      Analogue Scale, and the consumption of analgesics was also reviewed. RESULTS: No
      significant difference in perineal pain perception between the groups was
      observed in Verbal Descriptive Pain Scale. Although the mean Visual Analogue
      Scale and the accumulative mean consumption of paracetamol were generally lower
      in the intervention group, statistical significance was not reached. CONCLUSIONS:
      There is no evidence so far to conclude that ear acupressure can effectively
      relieve perineal pain based on the statistical results. Further research is
      suggested to explore whether the effectiveness of pain relief is affected by the
      frequency and duration of acupressure point stimulation. RELEVANCE TO CLINICAL
      PRACTICE: Training of midwives to perform this intervention is easy to achieve,
      but further evidence is required to prove its effectiveness.

PMID- 24286543
TI  - ACPA fine-specificity profiles in early rheumatoid arthritis patients do not
      correlate with clinical features at baseline or with disease progression.
AB  - INTRODUCTION: Autoantibodies against citrullinated peptides/proteins (ACPA) are
      found in approximately 75% of the sera of patients with rheumatoid arthritis
      (RA). The RA-specific ACPA are frequently present prior to disease onset and
      their presence associates with a more erosive disease course. ACPA can therefore
      be used to aid the diagnosis and prognosis of RA. Recently, it became clear that
      ACPA are very heterogeneous, both in an individual patient and among different
      patients. The aim of this study was to investigate whether clinically meaningful
      ACPA profiles exist in early RA patients. METHODS: Twenty citrullinated peptides
      and the corresponding non-citrullinated control peptides were immobilized on
      microarray sensor chips. Sera from 374 early arthritis patients were analyzed by
      surface plasmon resonance imaging (iSPR) of biomolecular interactions on the
      sensor chip. RESULTS: Cluster analysis of the reactivities with the citrullinated
      peptides, after subtraction of the reactivities with the corresponding control
      peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12
      distinct ACPA profiles. The association of the 5 most frequent profiles with
      clinical features at diagnosis and during the disease course was examined,
      showing no statistically significant associations. CONCLUSIONS: Compared to the
      detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early
      arthritis patients did not reveal associations with disease activity and
      progression scores.

PMID- 24286544
TI  - Experience of treating high risk prostate hyperplasia patients with a HPS120
      laser.
AB  - BACKGROUND: The aim of this study was to investigate the effects and safety of
      120 watt PVP surgery for the high risk prostate hyperplasia patients. METHODS:
      120 watt PVP surgery was performed on 120 cases of high risk prostate hyperplasia
      patients. The assessment included the operation time, energy consumed, hemoglobin
      changes, and serum salt concentration, whether to keep urinary catheter,
      hospitalization time, and complications after the operation. International
      Prostate Symptom Scoring (IPSS), the maximum urine flow rate (Qmax) and residual
      urine volume (RUV) were conducted preoperatively and postoperatively for the
      patients. RESULTS: There were 30% of patients taking oral anti-coagulant drug (n
      = 36), 88 cases with abnormal ECGs. All the patient's internal diseases, include
      the cardiovascular disease (42/120), the hypertension (56/120), the respiratory
      system diseases (51/120), the cerebrovascular diseases (39/120), anemia (24/120),
      liver or kidney dysfunction (16/120), diabetes (18/120), hypoproteinemia (15/120)
      were under controlled. The average age, prostate volume and energy consumed was
      82.8 +/- 8.6 (70-96) years, 66.1 +/- 25.3 (30-160) ml, and 224 +/- 85 (31-596) kJ
      respectively. The average follow-up time was 20.8 +/- 3.2 (18-24) months. The
      incidence of bladder neck contracture and urethral stricture were 1.7% and 0.8%
      respectively, no prostate cancer occurred during the subsequent follow-up period.
      CONCLUSIONS: 120 watt PVP surgery can safely and effectively alleviate the
      urination parameters of high risk prostate hyperplasia patients. The surgical
      process is safe and effective, and is not affected by the various internal
      diseases or the use of oral anti-coagulant drugs.

PMID- 24286545
TI  - Hormonal contraception and female pain, orgasm and sexual pleasure.
AB  - INTRODUCTION: Almost half of all pregnancies in the United States are
      unintentional, unplanned, or mistimed. Most unplanned pregnancies result from
      inconsistent, incorrect, or nonuse of a contraceptive method. Diminished sexual
      function and pleasure may be a barrier to using hormonal contraception. AIM: This
      study explores sexual function and behaviors of women in relation to the use of
      hormonal vs. nonhormonal methods of contraception. METHODS: Data were collected
      as part of an online health and sexuality study of women. MAIN OUTCOME MEASURES:
      Main outcomes variables assess frequencies in two domains: (i) sexual function
      (proportion of sexual events with experiences of pain or discomfort, arousal,
      contentment and satisfaction, pleasure and enjoyment, lubrication difficulty, and
      orgasm) and (ii) sexual behavior (number of times engaged in sexual activity,
      proportion of sexual events initiated by the woman, and proportion of sexual
      events for which a lubricant was used). Sociodemographic variables and
      contraceptive use were used as sample descriptors and correlates. The recall
      period was the past 4 weeks. RESULTS: The sample included 1,101 women with
      approximately half (n = 535) using a hormonal contraceptive method exclusively or
      a combination of a hormonal and nonhormonal method, and about half (n = 566)
      using a nonhormonal method of contraception exclusively. Hierarchical regression
      analyses were conducted to examine the relation of hormonal contraceptive use to
      each of the dependent variables. Women using a hormonal contraceptive method
      experienced less frequent sexual activity, arousal, pleasure, and orgasm and more
      difficulty with lubrication even when controlling for sociodemographic variables.
      CONCLUSIONS: This study adds to the literature on the potential negative sexual
      side effects experienced by many women using hormonal contraception. Prospective
      research with diverse women is needed to enhance the understanding of potential
      negative sexual side effects of hormonal contraceptives, their prevalence, and
      possible mechanisms. Clinical and counseling implications are discussed.

PMID- 24286546
TI  - [Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory
      idiopathic overactive bladder management].
AB  - OBJECTIVES: Provide guidelines for practical usage of botulinum toxin type A
      (BoNTA) for refractory idiopathic Overactive Bladder management. PATIENTS AND
      METHODS: Guidelines using formalized consensus guidelines method. These
      guidelines have been validated by a group of 13 experts quoting proposals,
      subsequently reviewed by an independent group of experts. RESULTS: In the case of
      patients with urinary tract infection, it must be treated and injection
      postponed. Before proposing an injection, it is recommended to ensure the
      feasibility and acceptability of self-catheterisation by patient. The injection
      can be performed after local anesthesia of the bladder and urethra (lidocaine),
      supplemented where necessary by nitrous oxide inhalation and sometimes under
      general anesthesia. Injection is performed in the operating room or endoscopy
      suite. The bladder should not be too filled (increased risk of perforation).
      Treatment should be applied in 10 to 20 injections of 0.5 to 1mL homogeneously
      distributed in the bladder at a distance from the urethral orifices. It is not
      recommended to leave a urinary catheter in place except in cases of severe
      hematuria. The patient should be monitored until resumption of micturition. After
      the first injection, an appointment must be scheduled within 3 months
      (micturition diary, uroflowmetry, measurement of residual urine and urine
      culture). Performance of self-catheterisation should be questioned in the case of
      a symptomatic post-void residual and/or a residue>200mL. A new injection may be
      considered when the clinical benefit of the previous injection diminishes
      (between 6 and 9 months). A period of three months must elapse between each
      injection. CONCLUSIONS: Implementation of these guidelines may promote best
      practice usage of BoNTA with optimal risk/benefit ratio.

PMID- 24286547
TI  - [French language validation of the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Questionnaire - IUGA revised (PISQ-IR)].
AB  - OBJECTIVES: To report a linguistically validated French version of the PISQ-IR
      (the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire IUGA-Revised).
      METHODS: PISQ-IR is a valid, reliable, and responsive measure of sexual function
      in both sexually active or inactive women with pelvic floor disorders. Validation
      process was performed according the IUGA guidelines. The French version of the
      PISQ-IR was developed after two independent translations (English>French), one
      back translation (French>English), cognitive debriefing with a sample of 25 women
      with pelvic floor disorders attending the gynecologic clinic in the university
      hospital of Nimes and a critical review by experts in the field of urogynecology
      and sexuality. RESULTS: The PISQ-IR is a self-administered questionnaire, which
      overcomes some shortcomings of the initial version. Questionnaire includes 20
      questions, the first one to clarify sexual activity: part 1 of the questionnaire
      is for non-sexually active women and contains 5 questions and the second part is
      for sexually active women and contains 12 or 14 questions depending on whether or
      not the women has a partner. CONCLUSION: This paper reports the linguistically
      validated French version of the PISQ-IR. Psychometric validation of the French
      PISQ-IR is currently ongoing and when completed, the scoring system will be
      shortly published in addition to the definitive version of the questionnaire.

PMID- 24286548
TI  - [Surgical site infections in vaginal prolapse surgery].
AB  - INTRODUCTION: Vaginal prolapse surgery is at high risk of surgical site
      infections (SSI) because it's a "clean-contaminated surgery" and it's frequently
      associated with implantation of meshes. OBJECTIVES: To evaluate the rate of SSI
      and associated risk factors in vaginal prolapse surgery with mesh support.
      METHODS: In a retrospective unicenter study, two groups of patients were operated
      by vaginal route for a pelvic floor reconstructive surgery with mesh support.
      Colporraphy was made by classic surgical sutures non-coated (Monosyn((r)) 3/0, B
      Braun) in the first group, and surgical sutures coated with triclosan in the
      second group. We collected risk factors of SSIs using the procedure of the CCLIN
      and analyzed the occurrence of SSIs with a statistical comparative univariate
      analysis. RESULTS: Study included 78 patients in the first group and 72 in the
      second group. SSIs total rate was 2.6 % (4 of 150), as part of 3 in the group
      with surgical sutures non-coated and one in the group with surgical sutures
      coated with triclosan (P=0.62). CONCLUSION: In our study, SSIs rate in vaginal
      prolapse surgery was twice higher than classic gynecologic surgery. As the
      interest of using a surgical suture coated with triclosan to reduce SSI has not
      been demonstrated statistically, we can't recommend it.

PMID- 24286549
TI  - [Influence of body mass index on the outcomes of robotic-assisted laparoscopic
      sacrocolpopexy: a comparative retrospective study].
AB  - OBJECTIVE: The aim of our study was to assess the impact of body mass index (BMI)
      on a robot-assisted laparoscopic sacrocolpopexy (RALS) to treat genital prolapse.
      METHODOLOGY: The study focused on a group of 56 women who went through a robot
      assisted laparoscopic sacrocolpopexy (RALS) between 2009 and 2013. Patients were
      divided into 3 groups according to their BMI (kg/m(2)): BMI<25 (n=28), 25<=BMI<30
      (n=16), BMI>=30 (n=12). The operating parameters, results and short-term
      complications were analysed according to the patients' BMI. RESULTS: The median
      BMI was 22.5kg/m(2) in group 1, 26.1kg/m(2) in group 2, and 31.6kg/m(2) in group
      3 (P<0.001). The operation time was respectively 250 minutes (130-380), 230
      minutes (150-410) and 255 minutes (170-370), for groups 1, 2 and 3 (P=0.689). The
      3 groups spent 4 days in the hospital (P=0.562). Only one laparotomy in group 3
      was reported (P=0.214). The rate of early complications was similar in groups 1,
      2 and 3 with 3/28, 0/16 and 0/12 respectively. Anatomical short-term results were
      identical in the 3 groups with a satisfactory anatomical correction in 100% of
      all cases (ICS POP-Q<2). CONCLUSION: In this small group, we observed that the
      BMI had no impact neither on the operation time nor on the rate of complication.

PMID- 24286550
TI  - [Evaluation of the management of erectile and ejaculatory dysfunction in a series
      of 90 patients with spinal cord injuries].
AB  - OBJECTIVE: To evaluate the erectile dysfunction and ejaculatory on patients
      injured in conus medullaris (CMI) and the efficacy of treatment. METHODS: Ninety
      patients with injured conus medullaris underwent a retrospective and monocentric
      study. They have all an assessment of erectile dysfunction and ejaculatory by the
      International Index of Erectile Function (IIEF-15) and a clinic scenario. We
      evaluated the erection by a clinical scoring scale (Shrameck). Seventy-seven out
      of 90 (85.55%) had therapeutic tests to restore erection: prostaglandin (PGE1),
      phosphodiesterase type 5 inhibitors (PDE5) and Papaverine. Seventy-four out of 90
      (82.22%) underwent a penile stimulation tests (VM) more or less associated with
      Midodrine((r)) (alpha mimetic) to cause ejaculation with a systematic search of
      spermatozoa in urine. Data were entered and analyzed using Microsoft Office
      Excel. RESULTS: Ninety patients with a complete lesion of the sacral metameres
      (S2S3S4) were included. They were responding to PGE1, PDE5, respectively 81.63%
      and 30.76%. The association VM/Midodrine((r)) improves ejaculation in 52.63% of
      cases. Orgasm is absent in all our CMI. CONCLUSION: In this series of BCM
      patients, we observed a good efficacy of PGE1 and PDE 5 on erection. We also
      observed positive results of vibromassage and alpha-agonists on ejaculation.

PMID- 24286551
TI  - The two-year outcome of the I-Stop TOMSTM transobturator sling in the treatment
      of male stress urinary incontinence in a single centre and prediction of outcome.
AB  - PURPOSE: The aim of this study was to present the results of the 2 year outcome
      of I-Stop TOMSTM transobturator sling for post-prostatectomy (UIPP) minor to
      moderate male urinary incontinence treatment. MATERIALS AND METHODS: A
      prospective, single center study, including 26 patients with minor to moderate
      IUPP and operated on using a suburethral sling (MS) TOMSTM (four arms) was
      performed. UIPP assessment was made preoperatively and 1 year postoperatively,
      using validated questionnaires (SF36 and ICIQ), number of pads daily, and the 24
      hours Pad-test (LPT). Telephone follow-up evaluation was performed in 21 patients
      over a 2 years period following surgery. RESULTS: Radical prostatectomy was
      performed 48.4 months earlier and average patient age was 67.3 years.
      Preoperatively, the mean number of pads used daily was 2.3 with an average weight
      loss of 207.1grams at LPT. At 1 year, ICIQ and SF36 scores significantly
      improved. Weight loss in the LPT as well as the number of pads significantly
      decreased (P<0.05). At 1 year, 13 patients were cured, 12 were improved, one
      reached improvement criteria, and 96.2% using a pad daily maximum. With more than
      a 2 year follow-up, 10/21 patients were dry, nine improved and two failed, and
      90.5% using 0 to 1 pad per day. CONCLUSIONS: The transobturator TOMSTM male sling
      is a simple and well-tolerated procedure permitting a significant improvement of
      UIPP, with 50% of patients achieving complete continence at 1 year
      postoperatively, these good results continued beyond 2 years. LEVEL OF EVIDENCE:
      4.

PMID- 24286552
TI  - [Surgical sphincterotomy in neurogenic bladder dysfunction with detrusor
      sphincter dyssynergia].
AB  - PURPOSE: To evaluate middle term results of surgical sphincterotomy in neurogenic
      bladder dysfunction with detrusor-sphincter dyssynergia. PATIENTS AND METHOD:
      Retrospective study about 44 patients whom underwent urinary sphincterotomy
      between January 2008 and September 2012. All patients had detrusor-sphincter
      dyssynergia. Mean age was 49.7 years. Seventy percent (n=30) of patients had
      spinal cord injury, 80% (n=34) underwent urethral stent. Sphincterotomy was
      performed in 55% (n=24) with monopolar resection and in 43% (n=19) with
      Revolix((r)) laser, after urethral stent withdrawal. RESULTS: Mean follow-up was
      30 months. Mean hospitalization stay was 5 days. Mean preoperative post-voiding
      residue (PVR) was 149mL and postoperative was 176mL. Twenty-nine percent (n=13)
      underwent new sphincterotomy with a final mean 116mL PVR, and a mean delay before
      new sphincterotomy of 9 months. Twenty percent (n=9) underwent other surgical
      procedure for sphincterotomy fail. CONCLUSION: In this series, we observed that
      surgical sphincterotomy is a well tolerated procedure, but with moderate
      immediate efficiency about 57%. It requires sometimes second procedure and long
      term follow-up in order not to fail to recognize stenosis, with best surgical
      success (80%).

PMID- 24286553
TI  - [Autonomic nervous system alteration in multiple sclerosis patients with urinary
      symptoms. Clinical, urodynamic and cardiovascular study].
AB  - OBJECTIVE: To assess symptoms related to autonomic nervous system alteration in a
      population of patients suffering from multiple sclerosis (MS) and presenting with
      urinary symptoms. PATIENTS AND METHODS: We investigated 65 patients (mean age
      47.5 years) suffering from MS, and presenting with urological dysfunction by
      means of symptom scores, urodynamic investigation, cardiovascular autonomic
      function tests (orthostatic hypotension testing, Valsalva test, deep breath test,
      cold pressor test) and sympathetic skin responses. RESULTS: Forty-five (69%)
      patients suffered from overactive bladder, 48 (73%) from voiding dysfunction, 14
      (21%) from urinary retention and 13 (20%) from fecal incontinence. Urodynamic
      investigation demonstrated overactive detrusor in 46 (70%) cases, and underactive
      detrusor in four (6%) cases. Twenty-five (38%) patients had dysautonomia without
      correlation neither with clinical or urodynamic data, nor gravity of multiple
      sclerosis (EDSS). CONCLUSION: In this series, the prevalence of dysautonomia was
      high in patients suffering from MS and presenting with urinary disorders.

PMID- 24286554
TI  - [Micturition and cognition].
AB  - PURPOSE: The physiopathology of the voiding and urinary continence was one of the
      hot topic of research these last few years. Unfortunately, anyone have already
      found a unique cause which could explain urinary incontinence (urge or stress).
      The concept of cognitive function highlights new ways of research to show the
      fundamental role of the cortex and the sub-cortex in these diseases. METHODS: A
      comprehensive literature review using Pubmed, Medline, Embase and Cochrane:
      "cognition, urinary tract, urinary continence, neuroimaging, IRMf, micturition,
      urge, brain factor and cognitive therapy". In all the articles, 72 really dealt
      with micturition and cognition. RESULTS: New imaging techniques allowed to show
      the relationship between the different brain area involved in the bladder control
      such as the periaqueductal gray, the hypothalamus, the insula, the anterior
      cingulated cortex and the prefrontal cortex. These cortical area are equally
      involved in cognition. An alteration of urinary continence implies a modification
      of activation of these cortical areas. CONCLUSION: A better knowledge of the
      cognitive side of micturition and urinary continence will allow to improve the
      treatment of their associated diseases.

PMID- 24286555
TI  - Editorial comment to Nocturnal polyuria and decreased serum testosterone: is
      there an association in men with lower urinary tract symptoms?

PMID- 24286557
TI  - An explanation of recommendation differences: illustrations from recent atrial
      fibrillation guidelines.
AB  - The development of guidelines and their use in all areas of medicine has greatly
      expanded in recent years. However, despite a shared evidence base,
      recommendations provided by different professional societies and healthcare
      authorities often vary considerably. The rapid advances in atrial fibrillation
      (AF) and the multiplicity of guidelines devoted to AF have made it particularly
      susceptible to this problem. Many nonmedical aspects are important in the
      development of guidelines, and without understanding them correct interpretation
      of guidelines is difficult. Conflicts of interest, the regulatory environment,
      and local data all influence guidelines. Nuanced wording, resource availability,
      and strategic purpose add complexity to guideline recommendations. This article
      reviews major AF guidelines from around the world and discusses aspects which
      have nothing to do with the scientific evidence base in order to help the
      practicing physician understand and make better use of differing guideline
      recommendations. 

PMID- 24286556
TI  - From GRID to gridlock: the relationship between scientific biomedical
      breakthroughs and HIV/AIDS policy in the US Congress.
AB  - INTRODUCTION: From the travel ban on people living with HIV (PLHIV) to resistance
      to needle exchange programmes, there are many examples where policy responses to
      HIV/AIDS in the United States seem divorced from behavioural, public health and
      sociological evidence. At its root, however, the unknowns about HIV/AIDS lie at
      biomedical science, and scientific researchers have made tremendous progress over
      the past 30 years of the epidemic by using antiretroviral therapy to increase the
      life expectancy of PLHIV almost to the same level as non-infected individuals;
      but a relationship between biomedical science discoveries and congressional
      responses to HIV/AIDS has not been studied. Using quantitative approaches, we
      directly examine the hypothesis that progress in HIV/AIDS biomedical science
      discoveries would have a correlative relationship with congressional response to
      HIV/AIDS from 1981 to 2010. METHODS: This study used original data on every bill
      introduced, hearing held and law passed by the US Congress relating to HIV/AIDS
      over 30 years (1981-2010). We combined congressional data with the most cited and
      impactful biomedical research scientific publications over the same time period
      as a metric of biomedical science breakthroughs. Correlations between
      congressional policy and biomedical research were then analyzed at the aggregate
      and individual levels. RESULTS: Biomedical research advancements helped shape
      both the level and content of bill sponsorship on HIV/AIDS, but they had no
      effect on other stages of the legislative process. Examination of the content of
      bills and biomedical research indicated that science helped transform HIV/AIDS
      bill sponsorship from a niche concern of liberal Democrats to a bipartisan
      coalition when Republicans became the majority party. The trade-off for that
      expansion has been an emphasis on the global epidemic to the detriment of
      domestic policies and programmes. CONCLUSIONS: Breakthroughs in biomedical
      science did associate with the number and types of HIV/AIDS bills introduced in
      Congress, but that relationship did not extend to the passage of laws or to
      hearings. When science matters, it cannot be separated from political
      considerations. An important implication of our work has been the depoliticizing
      role that science can play. Scientific breakthroughs helped to transform HIV/AIDS
      policy from a niche of liberal Democrats into bipartisan support for the global
      fight against the disease.

PMID- 24286558
TI  - Exploring the hologenome concept in marine bivalvia: haemolymph microbiota as a
      pertinent source of probiotics for aquaculture.
AB  - Haemolymph-associated microbiota of marine bivalves was explored for
      antibacterial activity against important aquaculture pathogens. A collection of
      843 strains were cultured from the haemolymph of four bivalve species
      (Crassostrea gigas, Mytilus edulis, Pecten maximus and Tapes rhomboides)
      collected by deep-sea diving in the Glenan Archipelago (France). Cell-free
      culture supernatants were investigated for antibacterial activity using the well
      diffusion assay. About 3% of haemolymph-associated cultivable bacteria displayed
      antibacterial activity toward Gram-negative pathogens. Among the active bacteria,
      Pseudoalteromonas strains exhibited the highest antibacterial activity. The cell
      free culture supernatant of one of them, named hCg-51, was able to inhibit the
      growth of bacterial pathogens even after drastic dilution (1 : 1024). Hemocyte
      survival was not significantly altered in the presence of the haemolymph
      associated strains assayed. Moreover, a dose-dependent beneficial effect on
      hemocyte survival rates was observed with the hCg-51 strain. These results
      suggest that haemolymph microbiota may participate in bivalve protection and
      therefore confer a health benefit on the host. As a result, the results highlight
      bivalve haemolymph microbiota as a promising novel source for aquaculture
      probiotics. This work also gives a first insight into the contribution of the
      haemolymph-associated microbiota as part of the bivalve 'hologenome'. 

PMID- 24286559
TI  - Editorial 2014.

PMID- 24286560
TI  - Why related bacterial species bloom simultaneously in the gut: principles
      underlying the 'Like will to like' concept.
AB  - The large intestine is host to a complex ecological community composed
      predominantly of obligate anaerobic bacteria belonging to the classes Bacteroidia
      and Clostridia. This community confers benefits through its metabolic activities
      and host interactions. However, a microbial imbalance (dysbiosis) characterized
      by a decreased abundance of Clostridia and a bloom of facultative anaerobic
      Proteobacteria is commonly observed during inflammation in the large bowel. Here
      we review recent insights into the principles that favour simultaneous increases
      in the abundance of closely related species belonging to the Proteobacteria
      during inflammation, which provides important clues for the rational design of
      strategies to treat dysbiosis. 

PMID- 24286561
TI  - Distensibility of the anal canal in patients with idiopathic fecal incontinence:
      a study with the Functional Lumen Imaging Probe.
AB  - BACKGROUND: Anatomical structures and their distensibility vary along the length
      of the anal canal. The anal sphincter muscles have dynamic properties that are
      not well-reflected by standard manometry. Abnormal distensibility of the anal
      canal may be of importance in idiopathic fecal incontinence (IFI). The functional
      lumen imaging probe (FLIP) allows detailed studies of the distensibility and
      axial variation of sphincters. We aimed at comparing segmental distensibility of
      the anal canal in patients with IFI and healthy subjects. METHODS: The FLIP was
      used for distension of the anal canal in 22 patients with IFI (17 female, age 27
      82 years) and 21 healthy volunteers (18 female, age 32-73 years). The
      distensibility was determined from changes in luminal diameter. Closure of the
      anal canal during voluntary squeeze was computed as the combined length of closed
      anal canal and time. Pressure-strain elastic modulus was computed at rest. KEY
      RESULTS: In all subjects, the proximal anal canal was the most distensible
      segment. During distension at rest and during squeeze the middle and distal anal
      canal became significantly larger in IFI than in healthy (F < 22.4, p < 0.05).
      The closure of the anal canal during voluntary squeeze did not differ between
      healthy (75.9 +/- 92.9 mm s) and IFI patients (90.4 +/- 105 mm s; p = 0.6).
      Compared with healthy, IFI patients had lower pressure-strain elastic modulus of
      the middle and distal (q > 4.5, p < 0.05) but not the proximal anal canal (q <
      0.7, p > 0.05). CONCLUSIONS & INFERENCES: Patients with IFI have increased
      distensibility of the middle and distal parts of the anal canal.

PMID- 24286562
TI  - Measurement of the migration of a focal knee resurfacing implant with
      radiostereometry.
AB  - BACKGROUND AND PURPOSE: Articular resurfacing metal implants have been developed
      to treat full-thickness localized articular cartilage defects. Evaluation of the
      fixation of these devices is mandatory. Standard radiostereometry (RSA) is a
      validated method for evaluation of prosthetic migration, but it requires that
      tantalum beads are inserted into the implant. For technical reasons, this is not
      possible for focal articular resurfacing components. In this study, we therefore
      modified the tip of an articular knee implant and used it as a marker for RSA,
      and then validated the method. MATERIAL AND METHODS: We modified the tip of a
      resurfacing component into a hemisphere with a radius of 3 mm, marked it with a
      1.0-mm tantalum marker, and implanted it into a sawbone marked with 6 tantalum
      beads. Point-motion RSA of the "hemisphere bead" using standard automated RSA as
      the gold standard was compared to manual measurement of the tip hemisphere. 20
      repeated stereograms with gradual shifts of position of the specimen between each
      double exposure were used for the analysis. The tip motion was compared to the
      point motion of the hemisphere bead to determine the accuracy and precision.
      RESULTS: The accuracy of the manual tip hemisphere method was 0.08-0.19 mm and
      the precision ranged from 0.12 mm to 0.33 mm. INTERPRETATION: The accuracy and
      precision for translations is acceptable when using a small hemisphere at the tip
      of a focal articular knee resurfacing implant instead of tantalum marker beads.
      Rotations of the implant cannot be evaluated. The method is accurate and precise
      enough to allow detection of relevant migration, and it will be used for future
      clinical trials with the new implant.

PMID- 24286563
TI  - A CT scan protocol for the detection of radiographic loosening of the glenoid
      component after total shoulder arthroplasty.
AB  - BACKGROUND AND PURPOSE: It is difficult to evaluate glenoid component
      periprosthetic radiolucencies in total shoulder arthroplasties (TSAs) using plain
      radiographs. This study was performed to evaluate whether computed tomography
      (CT) using a specific patient position in the CT scanner provides a better method
      for assessing radiolucencies in TSA. METHODS: Following TSA, 11 patients were CT
      scanned in a lateral decubitus position with maximum forward flexion, which
      aligns the glenoid orientation with the axis of the CT scanner. Follow-up CT
      scanning is part of our routine patient care. Glenoid component periprosthetic
      lucency was assessed according to the Mole score and it was compared to routine
      plain radiographs by 5 observers. RESULTS: The protocol almost completely
      eliminated metal artifacts in the CT images and allowed accurate assessment of
      periprosthetic lucency of the glenoid fixation. Positioning of the patient within
      the CT scanner as described was possible for all 11 patients. A radiolucent line
      was identified in 54 of the 55 observed CT scans and osteolysis was identified in
      25 observations. The average radiolucent line Mole score was 3.4 (SD 2.7) points
      with plain radiographs and 9.5 (SD 0.8) points with CT scans (p = 0.001). The
      mean intra-observer variance was lower in the CT scan group than in the plain
      radiograph group (p = 0.001). INTERPRETATION: The CT scan protocol we used is of
      clinical value in routine assessment of glenoid periprosthetic lucency after TSA.
      The technique improves the ability to detect and monitor radiolucent lines and,
      therefore, possibly implant loosening also.

PMID- 24286564
TI  - Minimal clinically important improvement (MCII) and patient-acceptable symptom
      state (PASS) in total hip arthroplasty (THA) patients 1 year postoperatively.
AB  - BACKGROUND AND PURPOSE: The increased use of patient-reported outcomes (PROs) in
      orthopedics requires data on estimated minimal clinically important improvements
      (MCIIs) and patient-acceptable symptom states (PASSs). We wanted to find cut
      points corresponding to minimal clinically important PRO change score and the
      acceptable postoperative PRO score, by estimating MCII and PASS 1 year after
      total hip arthroplasty (THA) for the Hip Dysfunction and Osteoarthritis Outcome
      Score (HOOS) and the EQ-5D. PATIENTS AND METHODS: THA patients from 16 different
      departments received 2 PROs and additional questions preoperatively and 1 year
      postoperatively. The PROs included were the HOOS subscales pain (HOOS Pain),
      physical function short form (HOOS-PS), and hip-related quality of life (HOOS
      QoL), and the EQ-5D. MCII and PASS were estimated using multiple anchor-based
      approaches. RESULTS: Of 1,837 patients available, 1,335 answered the preoperative
      PROs, and 1,288 of them answered the 1-year follow-up. The MCIIs and PASSs were
      estimated to be: 24 and 91 (HOOS Pain), 23 and 88 (HOOS-PS), 17 and 83 (HOOS
      QoL), 0.31 and 0.92 (EQ-5D Index), and 23 and 85 (EQ-VAS), respectively. MCIIs
      corresponded to a 38-55% improvement from mean baseline PRO score and PASSs
      corresponded to absolute follow-up scores of 57-91% of the maximum score in THA
      patients 1 year after surgery. INTERPRETATION: This study improves the
      interpretability of PRO scores. The different estimation approaches presented may
      serve as a guide for future MCII and PASS estimations in other contexts. The
      cutoff points may serve as reference values in registry settings.

PMID- 24286565
TI  - The natural history of the hemiarthroplasty for displaced intracapsular femoral
      neck fractures.
AB  - BACKGROUND: Numerous papers have been published on the medium- and long-term
      results of hemiarthroplasties (HAs) after femoral neck fracture in the elderly.
      We were not aware of any articles that describe the outcome of HA until the
      patient dies. METHODS: Between 1975 and 1989, 307 bipolar hemiarthroplasties were
      performed in 302 consecutive patients with a displaced femoral neck facture.
      Patients with osteoarthritis of the hip, rheumatoid arthritis (RA), or senile
      dementia were not included in the study. All patients were followed annually
      until they died or until they needed a revision operation. RESULTS: The mortality
      rate was 28% after 1 year, and 63% after 5 years. The last patient who did not
      need a revision operation died in October 2010. Revision operations for aseptic
      loosening, protrusion, or both had to be performed in 34 patients (16%). A
      difference in reoperation rate was observed between patients less than 75 years
      of age (38%) and those who were older (6%). INTERPRETATION: Apart from age below
      75 years, male sex appeared to be predictive of a revision operation. HA is a
      safe and relatively inexpensive treatment for patients over 75 years of age with
      a displaced femoral neck fracture.

PMID- 24286566
TI  - Dichotomous location of 160 atypical femoral fractures.
AB  - BACKGROUND AND PURPOSE: The risk of atypical fracture of the femur is associated
      with bisphosphonate use. While characterizing atypical fractures from a previous
      nationwide study in radiographic detail, we had the impression that the fractures
      were located either in the subtrochanteric region or in the shaft. We determined
      whether there is a dichotomy in this respect. PATIENTS AND METHODS: The distance
      between the atypical fractures and the lesser trochanter was measured on plain
      radiographs from 129 of 160 patients with atypical fractures, taken from 2008
      through 2010. Analysis of the distances measured showed 2 clusters, which were
      then analyzed with regard to bisphosphonate use and age. RESULTS: The
      distribution of the distances would be best described as 2 clusters, with a
      dichotomy at 8 cm. The proximal (subtrochanteric) cluster comprised 25 patients
      who were generally younger (median 71 years) than the 104 patients in the cluster
      with shaft fractures (median 80 years). The 95% CI for the difference between
      medians was 4-11 years. Of the patients with subtrochanteric fractures, 18 of 25
      used bisphosphonates as compared to 89 of 104 with shaft fractures.
      INTERPRETATION: The younger age and possibly smaller proportion of bisphosphonate
      users in the subtrochanteric cluster may be compatible with a greater influence
      of mechanical stress in the underlying pathophysiology of proximal fractures.

PMID- 24286567
TI  - Eliciting health state utilities for Dupuytren's contracture using a discrete
      choice experiment.
AB  - BACKGROUND AND PURPOSE: An internet-based discrete choice experiment (DCE) was
      conducted to elicit preferences for a wide range of Dupuytren's contracture (DC)
      related health states. An algorithm was subsequently developed to convert these
      preferences into health state utilities that can be used to assess DC's impact on
      quality of life and the value of its treatments. METHODS: Health state
      preferences for varying levels of DC hand severity were elicited via an internet
      survey from a sample of the UK adult population. Severity levels were defined
      using a combination of contractures (0, 45, or 90 degrees) in 8 proximal
      interphalangeal and metacarpophalangeal joints of the index, middle, ring, and
      little fingers. Right-handed, left-handed, and ambidextrous respondents indicated
      which hand was preferable in each of the 10 randomly-selected hand-pairings
      comparing different DC severity levels. For consistency across comparisons,
      anatomically precise digital hand drawings were used. To anchor preferences onto
      the traditional 0-1 utility scale used in health economic evaluations, unaffected
      hands were assigned a utility of 1.0 whereas the utility for a maximally affected
      hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking
      respondents to indicate what combination of attributes and levels of the EQ-5D-5L
      profile most accurately reflects the impact of living with such hand. Conditional
      logistic models were used to estimate indirect utilities, then rescaled to the
      anchor points on the EQ-5D-5L. RESULTS: Estimated utilities based on the
      responses of 1,745 qualified respondents were 0.49, 0.57, and 0.63 for completely
      affected dominant hands, non-dominant hands, or ambidextrous hands, respectively.
      Utility for a dominant hand with 90-degree contracture in t h e
      metacarpophalangeal joints of the ring and little fingers was estimated to be
      0.89. Separately, reducing the contracture of metacarpophalangeal joint for a
      little finger from 50 to 12 degrees would improve utility by 0.02.
      INTERPRETATION: DC is associated with substantial utility decrements. The
      algorithms presented herein provide a robust and flexible framework to assess
      utility for varying degrees of DC severity.

PMID- 24286568
TI  - Consensus document on prosthetic joint infections.

PMID- 24286569
TI  - Preoperative corticosteroid injections are associated with worse long-term
      outcome of surgical carpal tunnel release.
AB  - BACKGROUND AND PURPOSE: Failed closed treatment of carpal tunnel syndrome (CTS)
      is often followed by surgery. We investigated whether preoperative steroid
      injections could have a negative effect on the long-term outcome of the
      operation. PATIENTS AND METHODS: 174 hands (164 patients) were operated on by a
      single surgeon at Tartu University Hospital in 2005. The patients were
      interviewed by telephone 5-6 years after the operation. Self-reported data were
      gathered retrospectively concerning the number of steroid injections received
      before the surgery and the perceived regression of symptoms (on a 100-point
      numeric rating scale) at the time of interview. The patients were also asked
      about the presence of specific symptoms of CTS if regression of their symptoms
      had not been complete. RESULTS: 93 of the 174 hands had complete regression of
      symptoms. Each additional injection was associated with an increased risk of
      occurrence of pain (RR = 1.1, 95% CI: 1.02-1-2), paresthesiae (RR = 1.1, CI: 1.1
      1.2), and nocturnal awakenings (RR = 1.2, CI: 1.1-1.3). There was a weak
      association between the number of injections and the score given to regression of
      symptoms. INTERPRETATION: This is the first study to indicate that patients who
      received a greater number of local steroid injections preoperatively were more
      likely to have postoperative complaints associated with CTS.

PMID- 24286570
TI  - Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species
      lacking the Fanconi anaemia (FA) core complex.
AB  - The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL)
      repair. Among the FA core complex components, FANCM is believed to act as a
      damage sensor for the ICL-blocked replication fork and also as a molecular
      platform for FA core complex assembly and interaction with Bloom's syndrome (BS)
      complex that is thought to play an important role in the processing of DNA
      structures such as stalled replication forks. In the present study, we found that
      in silkworms, Bombyx mori, a species lacking the major FA core complex components
      (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and
      cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM)
      was phosphorylated in the middle regions, and the modification was associated
      with its subcellular localization. In addition, BmFancM interacted with Mhf1, a
      histone-fold protein, and Rmi1, a subunit of the BS complex, in the different
      regions. The interaction region containing at least these two protein-binding
      domains played an essential role in FancM-dependent resistance to MMC. Our
      results suggest that BmFancM also acts as a platform for recruitment of both the
      FA protein and the BS protein, although the silkworm genome seems to lose FAAP24,
      a FancM-binding partner protein in mammals. 

PMID- 24286571
TI  - Socio-economic predictors of performance in the Undergraduate Medicine and Health
      Sciences Admission Test (UMAT).
AB  - BACKGROUND: Entry from secondary school to Australian and New Zealand
      undergraduate medical schools has since the late 1990's increasingly relied on
      the Undergraduate Medicine and Health Sciences Admission Test (UMAT) as one of
      the selection factors. The UMAT consists of 3 sections - logical reasoning and
      problem solving (UMAT-1), understanding people (UMAT-2) and non-verbal reasoning
      (UMAT-3). One of the goals of using this test has been to enhance equity in the
      selection of students with the anticipation of an increase in the socioeconomic
      diversity in student cohorts. However there has been limited assessment as to
      whether UMAT performance itself might be influenced by socioeconomic background.
      METHODS: Between 2000 and 2012, 158,909 UMAT assessments were completed. From
      these, 118,085 cases have been identified where an Australian candidate was
      sitting for the first time during that period. Predictors of the total UMAT
      score, UMAT-1, UMAT-2 and UMAT-3 scores were entered into regression models and
      included gender, age, school type, language used at home, deciles for the Index
      of Relative Socioeconomic Advantage and Disadvantage score, the
      Accessibility/Remoteness Index of Australia (ARIA), self-identification as being
      of Aboriginal or Torres Strait Islander origin (ATSI) and current Australian
      state or territory of abode. RESULTS: A lower UMAT score was predicted by living
      in an area of relatively higher social disadvantage and lower social advantage.
      Other socioeconomic indicators were consistent with this observation with lower
      scores in those who self-identified as being of ATSI origin and higher scores
      evident in those from fee-paying independent school backgrounds compared to
      government schools. Lower scores were seen with increasing age, female gender and
      speaking any language other than English at home. Divergent effects of rurality
      were observed, with increased scores for UMAT-1 and UMAT-2, but decreasing UMAT-3
      scores with increasing ARIA score. Significant state-based differences largely
      reflected substantial socio-demographic differences across Australian states and
      territories. CONCLUSIONS: Better performance by Australian candidates in the UMAT
      is linked to an increase in socio-economic advantage and reduced
      disadvantage.This observation provides a firm foundation for selection processes
      at medical schools in Australia that have incorporated affirmative action
      pathways to quarantine places for students from areas of socio-economic
      disadvantage.

PMID- 24286572
TI  - Trends and characteristics of preventive care visits among commercially insured
      adolescents, 2003-2010.
AB  - OBJECTIVE: To examine preventive care visit patterns among commercially insured
      adolescents during 2003-2010. In 2005-2007, the Advisory Committee on
      Immunization Practices (ACIP) recommended 3 vaccines targeted at adolescents. We
      also investigate the relationship between preventive care visits and
      immunization. STUDY DESIGN: Data were drawn from the MarketScan database.
      Adolescents aged 11-21 continuously enrolled in the same insurance plan during
      the calendar year were included. We calculated the annual proportion of
      adolescents with at least 1 preventive and 1 vaccination-related visit.
      Longitudinal analyses were conducted by following the 1992 birth cohort for 8
      consecutive years. RESULTS: The proportion of adolescents making at least 1
      preventive visit increased from 24.6%-41.1% during 2003-2010. The rate of
      vaccination-related visits increased from 12.9%-26.3%. The magnitude of the
      increase in preventive and vaccination-related visits was greater during the
      years in which ACIP issued recommendations. The rates of preventive and
      vaccination-related visits were considerably higher among female and early
      adolescents and adolescents in managed care plans. Longitudinal analyses
      indicated that only 2.4% of adolescents had an annual preventive visit during the
      8 years. CONCLUSIONS: Yearly improvements in preventive care visits by
      adolescents were substantial. ACIP recommendations may be associated with this
      improvement. However, ongoing efforts are needed to improve the use and delivery
      of preventive care services.

PMID- 24286573
TI  - Methotrexate: new uses for an old drug.

PMID- 24286574
TI  - Epidemiology of heart failure and scope of the problem.
AB  - Heart failure (HF) is typically a chronic disease, with progressive deterioration
      occurring over a period of years or even decades. HF poses an especially large
      public health burden. It represents a new epidemic of cardiovascular disease,
      affecting nearly 5.8 million people in the United States, and over 23 million
      worldwide. In the present article, our goal is to describe the most up-to-date
      epidemiology of HF in the United States and worldwide, and challenges facing HF
      prevention and treatment. 

PMID- 24286575
TI  - Pathophysiology and etiology of heart failure.
AB  - Heart failure is a clinical syndrome that is heterogeneous in both
      pathophysiology and etiology. This article describes some of the common
      mechanisms underlying heart failure, and reviews common causes. Informative
      diagnostic testing is reviewed. 

PMID- 24286576
TI  - The renin-angiotensin-aldosterone system and heart failure.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the
      pathophysiology of heart failure with reduced ejection fraction (HFrEF).
      Targeting components of the RAAS has produced significant improvements in
      morbidity and mortality. Angiotensin-converting enzyme (ACE) inhibitors remain
      first-line therapy for all patients with a reduced ejection fraction. Angiotensin
      receptor blockers may be used instead of ACE inhibitors in patients with
      intolerance, or in conjunction with ACE inhibitors to further reduce symptoms.
      Recent data support broader indications for aldosterone antagonists in heart
      failure, and the combination of an ACE-inhibitor and aldosterone antagonist has
      become the preferred strategy for dual blockade of the RAAS. 

PMID- 24286578
TI  - Evaluation of patients with heart failure.
AB  - Heart failure is one of the most prevalent cardiovascular diseases in the United
      States, and is associated with significant morbidity, mortality, and costs.
      Prompt diagnosis may help decrease mortality, hospital stay, and costs related to
      treatment. A complete heart failure evaluation comprises a comprehensive history
      and physical examination, echocardiogram, and diagnostic tools that provide
      information regarding the etiology of heart failure, related complications, and
      prognosis in order to prescribe appropriate therapy, monitor response to therapy,
      and transition expeditiously to advanced therapies when needed. Emerging
      technologies and biomarkers may provide better risk stratification and more
      accurate determination of cause and progression. 

PMID- 24286577
TI  - The sympathetic nervous system and heart failure.
AB  - Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic
      nervous system and abnormal responsiveness of the parasympathetic nervous system.
      Studies in the 1980s and 1990s demonstrated that inhibition of the renin
      angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors
      improved symptoms and mortality in HF resulting from systolic dysfunction, thus
      providing a framework to consider the use of beta-blockers for HF therapy,
      contrary to the prevailing wisdom of the time. Against this backdrop, this
      article reviews the contemporary understanding of the sympathetic nervous system
      and the failing heart. 

PMID- 24286579
TI  - Management of ACCF/AHA Stage A and B patients.
AB  - Heart failure remains a major health problem in the United States, affecting 5.8
      million Americans. Its prevalence continues to rise due to the improved survival
      of patients. Despite advances in treatment, morbidity and mortality remain very
      high, with a median survival of about 5 years after the first clinical symptoms.
      This article describes the causes, classification, and management goals of heart
      failure in Stages A and B. 

PMID- 24286580
TI  - Management of ACCF/AHA Stage C heart failure.
AB  - ACC Stage C heart failure includes those patients with prior or current symptoms
      of heart failure in the context of an underlying structural heart problem who are
      primarily managed with medical therapy. Although there is guideline-based medical
      therapy for those with heart failure with reduced ejection fraction (HFrEF),
      therapies in heart failure with preserved ejection fraction (HFpEF) have thus far
      proven elusive. Emerging therapies such as serelaxin are currently under
      investigation and may prove beneficial. The role of advanced surgical therapies,
      such as mechanical circulatory support, in this population is not well defined.
      Further investigation is warranted for these therapies in patients with Stage C
      heart failure. 

PMID- 24286581
TI  - Management of the ACC/AHA Stage D patient: cardiac transplantation.
AB  - Over the last 4 decades, cardiac transplantation has become the preferred therapy
      for select patients with end-stage heart disease. Heart transplantation is
      indicated in patients with heart failure despite optimal medical and device
      therapy, manifesting as intractable angina, refractory heart failure, or
      intractable ventricular arrhythmias. This article provides an overview of heart
      transplantation in the current era, focusing on the evaluation process for heart
      transplantation, the physiology of the transplanted heart, immunosuppressive
      regimens, and early and long-term complications. 

PMID- 24286582
TI  - Management of the ACC/AHA Stage D patient: mechanical circulatory support.
AB  - From humble beginnings in 1963 with a single desperately ill patient, mechanical
      circulatory support has expanded exponentially to where it is a viable
      alternative for advanced heart failure patients. Some of these patients are
      awaiting transplant but others will have a mechanical heart pump as their
      ultimate treatment. The history of MCS devices is reviewed, along with the 4
      trials that define the modern era of circulatory support. The practical aspects
      of life with an MCS device are reviewed and common problems encountered with MCS
      devices. Future trends including miniaturization and development of completely
      contained MCS systems are reviewed. 

PMID- 24286583
TI  - Arrhythmias and heart failure.
AB  - Atrial fibrillation and ventricular tachyarrhythmias are frequently seen in
      patients with heart failure, and complicate the management of such patients. Both
      types of arrhythmia lead to increased morbidity and mortality, and often prove to
      be challenging issues to manage. The many randomized studies that have been
      performed in patients with these conditions and concomitant heart failure have
      helped in designing optimal treatment strategies. 

PMID- 24286584
TI  - Sudden cardiac death in heart failure.
AB  - Sudden cardiac deaths account for 350,000 to 380,000 deaths in the United States
      annually. Implantable cardioverter-defibrillators have improved sudden death
      outcomes in patients with heart failure, but only a minority of patients with
      defibrillators receives appropriate therapy for ventricular arrhythmias. The risk
      prediction for sudden death and selection of patients for defibrillators is based
      largely on left ventricular ejection fraction and heart failure symptoms because
      there are no other risk stratification tools that can determine the individual
      patients who will derive the greatest benefit. There are several other
      pharmacologic strategies designed to prevent sudden death in patients with heart
      failure. 

PMID- 24286585
TI  - Managing acute decompensated heart failure.
AB  - Acute decompensated heart failure may occur de novo, but it most often occurs as
      an exacerbation of underlying chronic heart failure. Hospitalization for heart
      failure is usually a harbinger of a chronic disease that will require long-term,
      ongoing medical management. Leaders in the field generally agree that repeated
      inpatient admissions for treatment reflect a failure of the health care delivery
      system to manage the disease optimally. Newer management strategies focus on
      ameliorating symptoms by optimizing the hemodynamics, restoring neurohormonal
      balance, and making frequent outpatient adjustments when needed. 

PMID- 24286586
TI  - Heart failure with preserved ejection fraction: an ongoing enigma.
AB  - Heart failure with preserved ejection fraction (HFpEF) is a complex clinical
      syndrome based on traditional heart failure symptoms with documentation of
      increased left ventricular filling pressures and preserved left ventricular
      ejection fraction. The exact mechanisms that induce HFpEF are not known. End
      diastolic ventricular stiffness does not seem to be acting alone. Substantial
      mortality exists compared with healthy age-matched controls, as well as
      significant health care expenditures on hospitalizations and readmissions. This
      article reviews the epidemiology, pathophysiology, and treatment of heart failure
      with preserved ejection fraction (HFpEF). Current practice guidelines focus on
      remedying volume overload, aggressively controlling hypertension, and treatment
      of comorbid conditions that contribute to decompensation. 

PMID- 24286587
TI  - Adjunctive therapy and management of the transition of care in patients with
      heart failure.
AB  - Heart failure is a costly and difficult disease to treat. However, new metrics
      make it an imperative to keep these patients out of the hospital. Implementing
      and maintaining patients on successful treatment plans is difficult. A multitude
      of factors make transitioning care to the outpatient setting difficult. A careful
      and well-orchestrated team of cardiologists, general practitioners, nurses, and
      ancillary support staff can make an important difference to patient care. A
      strong body of literature supports the use of pharmacologic therapy, and evidence
      based therapies can improve mortality and quality of life, and reduce hospital
      admissions. Adjunctive therapies can be equally important. 

PMID- 24286588
TI  - Preface. Heart failure.

PMID- 24286589
TI  - Modeling human neurological disorders with induced pluripotent stem cells.
AB  - Human induced pluripotent stem (iPS) cells obtained by reprogramming technology
      are a source of great hope, not only in terms of applications in regenerative
      medicine, such as cell transplantation therapy, but also for modeling human
      diseases and new drug development. In particular, the production of iPS cells
      from the somatic cells of patients with intractable diseases and their subsequent
      differentiation into cells at affected sites (e.g., neurons, cardiomyocytes,
      hepatocytes, and myocytes) has permitted the in vitro construction of disease
      models that contain patient-specific genetic information. For example, disease
      specific iPS cells have been established from patients with neuropsychiatric
      disorders, including schizophrenia and autism, as well as from those with
      neurodegenerative diseases, including Parkinson's disease and Alzheimer's
      disease. A multi-omics analysis of neural cells originating from patient-derived
      iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of
      neurological diseases that have heretofore been unknown. In addition, large-scale
      screening of chemical libraries with disease-specific iPS cells is currently
      underway and is expected to lead to new drug discovery. Accordingly, this review
      outlines the progress made via the use of patient-derived iPS cells toward the
      modeling of neurological disorders, the testing of existing drugs, and the
      discovery of new drugs. The production of human induced pluripotent stem (iPS)
      cells from the patients' somatic cells and their subsequent differentiation into
      specific cells have permitted the in vitro construction of disease models that
      contain patient-specific genetic information. Furthermore, innovations of gene
      editing technologies on iPS cells are enabling new approaches for illuminating
      the pathogenic mechanisms of human diseases. In this review article, we outlined
      the current status of neurological diseases-specific iPS cell research and
      described recently obtained knowledge in the form of actual examples. 

PMID- 24286590
TI  - High concentration capsaicin for treatment of peripheral neuropathic pain: effect
      on somatosensory symptoms and identification of treatment responders.
AB  - BACKGROUND: Pain is usually assessed by spontaneous pain ratings. Time-dependent
      (brief attacks) or evoked (allodynia) phenomena, common in neuropathic pain, are
      not captured. To evaluate the overall effectiveness of a treatment, improvement
      of all sensory symptoms should be measured. Since the pattern of sensory
      abnormalities might hint at the underlying mechanisms of pain, this baseline
      information may aid in predicting the treatment effect. Data on sensory
      neuropathic abnormalities (painDETECT questionnaire) were analyzed aiming to (1)
      evaluate the frequency of neuropathic symptoms in different peripheral
      neuropathic pain syndromes, (2) assess the effect of capsaicin 8% patch on
      neuropathic symptoms and (3) identify treatment responders based on baseline
      values. METHODS: Data analysis of a prospective 12 week non-interventional trial
      in peripheral neuropathic pain treated with capsaicin 8% cutaneous patch. Average
      pain intensity during the past 24 hours, pain descriptors and qualities of
      neuropathic pain were assessed to characterize the patients' sensory symptoms at
      baseline and to document changes. RESULTS: (1) Characteristic symptoms of
      neuropathic pain were present in all peripheral neuropathic pain syndromes, but
      frequencies varied in the individual syndromes. (2) Topical capsaicin 8%
      treatment significantly reduced the overall pain intensity and resulted in a
      reduction of sensory abnormalities. (3) Short disease duration predicted a better
      treatment effect. High painDETECT scores, the presence of burning and pressure
      evoked pain were weakly associated with treatment response. CONCLUSIONS: Topical
      capsaicin 8% treatment effectively reduced sensory abnormalities in peripheral
      neuropathic pain. The association of sensory symptoms and treatment response aids
      in understanding the mechanism of action of high concentration capsaicin. It is,
      however, not possible to use sensory symptom patterns to predict treatment
      response to capsaicin on an individual level. LIMITATIONS: Completion of
      painDETECT was optional and therefore data was not available for all patients.
      Further studies for confirmation of these results are needed.

PMID- 24286591
TI  - Hypoxic exercise training improves cardiac/muscular hemodynamics and is
      associated with modulated circulating progenitor cells in sedentary men.
AB  - BACKGROUND: Circulating progenitor cells (CPCs) improve cardiovascular function
      and organ perfusion by enhancing the capacities of endothelial repair and
      neovasculogenesis. This study investigates whether exercise regimens with/without
      hypoxia affect cardiac and muscular hemodynamics by modulating CPCs and
      angiogenic factors. METHODS: Forty sedentary males were randomly divided into
      hypoxic (HT, n=20) and normoxic (NT, n=20) training groups. The subjects were
      trained on a bicycle ergometer at 60%VO(2max) under 15% (HT) or 21% (NT) O2
      conditions for 30 min daily, five days weekly for five weeks. RESULTS: After the
      five-week interventions, the HT group exhibited a larger improvement in aerobic
      capacity than the NT group. Furthermore, the HT regimen (i) enhanced cardiac
      output (Q(H)) and perfusion (Q(M))/oxygenation of vastus lateralis during
      exercise; (ii) increased levels of CD34(+)/KDR(+)/CD117(+),
      CD34(+)/KDR(+)/CD133(+), and CD34(+)/KDR(+)/CD31(+) cells in blood; (iii)
      promoted the proliferative capacity of these CPC subsets, and (iv) elevated
      plasma nitrite/nitrate, stromal cell-derived factor-1 (SDF-1), matrix
      metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A)
      concentrations. Despite the lack of changes in Q(H) and the number or
      proliferative capacity of CD34(+)/KDR(+)/CD117(+) or CD34(+)/KDR(+)/CD31(+)
      cells, the NT regimen elevated both Q(M) and plasma nitrite/nitrate levels and
      suppressed the shedding of endothelial cells (CD34(
      )/KDR(+)/phosphatidylserine(+) cells). CONCLUSIONS: The HT regimen improves
      cardiac and muscular hemodynamic adaptations, possibly by promoting the
      mobilization/function of CPCs and the production of angiogenic factors.

PMID- 24286592
TI  - Substance P in heart failure: the good and the bad.
AB  - The tachykinin, substance P, is found primarily in sensory nerves. In the heart,
      substance P-containing nerve fibers are often found surrounding coronary vessels,
      making them ideally situated to sense changes in the myocardial environment.
      Recent studies in rodents have identified substance P as having dual roles in the
      heart, depending on disease etiology and/or timing. Thus far, these studies
      indicate that substance P may be protective acutely following ischemia
      reperfusion, but damaging long-term in non-ischemic induced remodeling and heart
      failure. Sensory nerves may be at the apex of the cascade of events leading to
      heart failure, therefore, they make a promising potential therapeutic target that
      warrants increased investigation. 

PMID- 24286593
TI  - Nucleic acid delivery by cell penetrating peptides derived from dengue virus
      capsid protein: design and mechanism of action.
AB  - Cell penetrating peptides (CPPs) can be used as drug delivery systems for
      different therapeutic molecules. In this work two novel CPPs, pepR and pepM,
      designed from two domains of the dengue virus (DENV) capsid protein, were studied
      for their ability to deliver nucleic acids into cells as non-covalently bound
      cargo. Translocation studies were performed by confocal microscopy in HepG2, BHK
      and HEK cell lineages, astrocytes and peripheral blood mononuclear cells.
      Combined studies in HepG2 cells, astrocytes and BHK cells, at 4 and 37  degrees C
      or using specific endocytosis inhibitors, revealed that pepR and pepM use
      distinct internalization routes: pepM translocates lipid membranes directly,
      while pepR uses an endocytic pathway. To confirm these results, a methodology was
      developed to monitor the translocation kinetics of both peptides by real-time
      flow cytometry. Kinetic constants were determined, and the amount of nucleic
      acids delivered was estimated. Additional studies were performed in order to
      understand the molecular bases of the peptide-mediated translocation. Peptide
      nucleic acid and peptide-lipid membrane interactions were studied quantitatively
      based on the intrinsic fluorescence of the peptides. pepR and pepM bound ssDNA to
      the same extent. Partition studies revealed that both peptides bind
      preferentially to anionic lipid membranes, adopting an alpha-helical
      conformation. However, fluorescence quenching studies suggest that pepM is deeply
      inserted into the lipid bilayer, in contrast with pepR. Moreover, only pepM is
      able to promote the fusion and aggregation of vesicles composed of zwitterionic
      lipids. Altogether, the results show that DENV capsid protein derived peptides
      serve as good templates for novel CPP-based nucleic acid delivery strategies,
      defining different routes for cell entry. 

PMID- 24286595
TI  - Dissection of two major components of the post-zygotic hybridization barrier in
      rice endosperm.
AB  - A post-zygotic hybridization barrier is often observed in the endosperm of seeds
      produced by interspecific or interploidy crosses. In Arabidopsis thaliana, for
      example, hybrid endosperm from both types of cross shows altered timing of
      cellularization and an altered rate of nuclear divisions. Therefore, it has been
      proposed that interspecific and interploidy crosses share common molecular
      mechanisms for establishment of an effective species barrier. However, these two
      types of hybridization barrier may be initiated by different intrinsic cues: the
      interspecific cross barrier arises after hybridization of genomes with
      differences in DNA sequences, while the interploidy cross barrier arises after
      hybridization of genomes with the same DNA sequences but differences in ploidy
      levels. In this study, we performed interploidy crosses to identify components of
      the post-hybridization barrier in the endosperm of rice. We performed an intra
      cultivar cross of autotetraploid (4n) * diploid (2n) rice, and found precocious
      cellularization and a decreased rate of nuclear division in the syncytial
      endosperm. By contrast, seeds from the reciprocal cross showed delayed
      cellularization and an increased rate of nuclear division. This differential
      effect on nuclear division rates contrasts with the outcome of rice interspecific
      crosses, which were previously shown to have altered timing of cellularization
      without any change in nuclear division rates. Thus, we propose that the post
      zygotic hybridization barrier in rice endosperm has two separable components,
      namely control of the timing of cellularization and control of the nuclear
      division rates in the syncytial stage of endosperm development.

PMID- 24286594
TI  - Positron emission tomography/computed tomography for optimized colon cancer
      staging and follow up.
AB  - OBJECTIVES: Optimal management of colon cancer (CC) requires detailed assessment
      of extent of disease. This study prospectively investigates the diagnostic
      accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed
      tomography (PET/CT) for staging and detection of recurrence in primary CC.
      MATERIAL AND METHODS: PET/CT for preoperative staging was performed in 66
      prospectively included patients with primary CC. Diagnostic accuracy for PET/CT
      and CT was analyzed. In addition to routine follow up, 42 stages I-III CC
      patients had postoperative PET/CT examinations every 6 months for 2 years.
      Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1),
      carcinoembryonic antigen, and liberated domain I of urokinase plasminogen
      activator receptor were analyzed. RESULTS: Accuracy for tumor, nodal, and
      metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66%
      (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60%
      (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I
      III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19%
      (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during
      the first 2 years. High preoperative TIMP-1 levels were associated with
      significant hazards toward risk of recurrence and shorter overall survival.
      CONCLUSIONS: This study indicates PET/CT as a valuable tool for staging and
      follow up in CC. TIMP-1 provided prognostic information potentially useful in
      selection of patients for intensive follow up.

PMID- 24286596
TI  - Contextualizing the findings of a systematic review on patient and carer
      experiences of dementia diagnosis and treatment: a qualitative study.
AB  - BACKGROUND: Involving service users in the systematic review process is seen as
      increasingly important. As systematic reviews often include studies from diverse
      settings and covering a time span of several decades, involving service users in
      consideration of applicability to specific populations or settings might make
      reviews more useful to practitioners and policymakers. OBJECTIVES: To test and
      contextualize the findings of a systematic review of qualitative studies looking
      at patient and carer experiences of diagnosis and treatment of dementia. METHODS:
      Results from the systematic review were discussed in focus groups and semi
      structured interviews with patient, public and professional participants in the
      South East of England. Analysis was guided by coding frameworks developed from
      the results of the systematic review. PARTICIPANTS: We recruited 27 participants,
      including three people with dementia, 12 carers, six service providers and five
      older people without dementia. RESULTS: Findings from the focus groups and
      interviews were consistent with those from the systematic review and suggest that
      our review findings were applicable to the local setting. We found some evidence
      that access to information and diagnostic services had improved but, as in the
      systematic review, post-diagnosis support was still often experienced as
      inadequate. CONCLUSIONS: Focus groups and interviews with service users and their
      representatives can provide useful contextual information. However, such
      strategies can require considerable investment of the part of the researcher in
      terms of time and resources, and more work is needed to refine strategies and
      establish the benefits for patients and the organization of services.

PMID- 24286597
TI  - Editorial comment to high percent tumor volume predicts biochemical recurrence
      after radical prostatectomy in pathological stage T3a prostate cancer with a
      negative surgical margin.

PMID- 24286598
TI  - Safety of medical male circumcision in human immunodeficiency virus-infected men
      in Rakai, Uganda.
AB  - OBJECTIVE: To assess the safety of medical male circumcision (MMC) among human
      immunodeficiency virus (HIV)-infected men with CD4 levels <350 cells/mm(3), CD4
      counts >= 350 cells/mm(3), and HIV-negative men. METHODS: Two hundred forty-two
      HIV-infected men and a sample of 262 HIV-negative consenting men aged 12 years or
      older who requested free MMC were enrolled in a prospective study. Blood for HIV
      testing and a CD4 count were collected before surgery. During weekly follow-up
      over 6 weeks, data were collected on wound healing and adverse events (AEs) by
      examination, and resumption of sex and condom use ascertained by interview.
      Surgery-related AEs were characterized by type, severity, management, and
      resolution. Chi-square and Fisher's exact tests were used to test for differences
      in AE proportions. RESULTS: Overall, only 2 of the 453 men experienced moderate
      AEs, a rate of 0.44 per 100 surgeries. No AE occurred among HIV-negative men,
      whereas the AE rate among HIV-infected men with CD4 counts >= 350 cells/mm(3) was
      0.79 per 100 surgeries, and among men with CD4 counts <350 cells/mm(3) the rate
      was 1.19 per 100 surgeries (P = .214). AE rates were comparable for all
      characteristics (P >.05). CONCLUSION: HIV-positive men can be safely included in
      MMC roll out programs without necessitating presurgery CD4 counts determination.

PMID- 24286599
TI  - Congenital spigelian hernia and ipsilateral cryptorchidism: raising awareness
      among urologists.
AB  - Spigelian hernias (SHs) are rare in the pediatric population. Although pediatric
      general surgeons often treat this defect, the increased association between a
      congenital SH and an ipsilateral undescended testis suggests that urologists may
      be the first provider encountering this entity. Knowledge of this condition is
      therefore important. We report one such case of a male infant referred to urology
      for an undescended testicle. Further investigation revealed the testicle to be
      within a congenital SH sac. Herein, we additionally review the literature
      concerning SHs associated with ipsilateral undescended testicles. 

PMID- 24286600
TI  - Active surveillance for low-risk prostate cancer in African American men: a multi
      institutional experience.
AB  - OBJECTIVE: To compare the outcomes of active surveillance (AS) series between
      African American men (AAM) and non-AAM diagnosed with low-risk prostate cancer at
      3 medical centers. METHODS: Between 2005 and 2012, 214 men accepted AS on the
      basis of favorable clinical features and parameters after initial and repeat
      biopsy. Failure was defined as increase in Gleason score >6, total positive cores
      >33%, maximum cancer volume in any core >50%, or a prostate-specific antigen >10
      ng/mL. Disease progression and overall AS failure were compared between the 2
      groups. RESULTS: Of 214 men, 75 were excluded, leaving 67 AAM and 72 non-AAM on
      AS. Median age at diagnosis was 64 and 67 years for AAM and non-AAM,
      respectively, and median follow-up was 34 and 46 months, respectively. During
      this time, 44 AAM (66%) remained on AS, and 23 (34%) underwent treatment, of whom
      6 (26%) were treated by patient choice and 17 (74%) because of disease
      progression. In the non-AAM group, 59 (82%) men remained on AS, and 13 (18%)
      underwent treatment, 8 (62%) were treated by patient choice and 5 (38%) because
      of disease progression. The 3-year freedom from overall treatment was 74% and did
      not differ by race (P = .06). The 3-year freedom from disease progression was
      85%, where AAM were at significantly higher risk of disease progression (hazard
      ratio = 3.8; 95% confidence interval: 1.4-10.4; P = .01). CONCLUSION: Our study
      suggests a higher disease progression rate in AAM who choose AS for low-risk
      prostate cancer compared with non-AAM, signifying a potential need for closer
      follow-up and more stringent enrollment criteria in AAM.

PMID- 24286601
TI  - Editorial comment.

PMID- 24286602
TI  - SIU/ICUD Consultation on Urethral Strictures: Dilation, internal urethrotomy, and
      stenting of male anterior urethral strictures.
AB  - Male urethral stricture is one of the oldest known urologic diseases, and
      continues to be a common and challenging urologic condition. Our objective was to
      review all contemporary and historial articles on the topic of dilation, internal
      urethrotomy, and stenting of male anterior urethral strictures. An extensive
      review of the scientific literature concerning anterior urethral
      urethrotomy/dilation/stenting was performed. Articles were included that met the
      criteria set by the International Consultation on Urological Diseases (ICUD)
      urethral strictures committee and were classified by level of evidence using the
      Oxford Centre for Evidence-Based Medicine criteria adapted from the work of the
      Agency for Health Care Policy and Research as modified for use in previous ICUD
      projects. Using criteria set forth by the ICUD, a committee of international
      experts in urethral stricture disease reviewed the literature and created a
      consensus statement incorporating levels of evidence and expert opinion in regard
      to dilation, internal urethrotomy, and stenting of male anterior urethral
      strictures. 

PMID- 24286604
TI  - Reply: To PMID 24286601.

PMID- 24286603
TI  - Initial treatment of men with newly diagnosed lower urinary tract dysfunction in
      the Veterans Health Administration.
AB  - OBJECTIVE: To examine initial treatments given to men with newly diagnosed lower
      urinary tract dysfunction (LUTD) within a large integrated health care system in
      the United States. METHODS: We used data from 2003 to 2009 from the Veteran's
      Health Administration to identify newly diagnosed cases of LUTD using established
      ICD-9CM codes. Our primary outcome was initial LUTD treatment (3 months),
      categorized as watchful waiting (WW), medical therapy (MT), or surgical therapy
      (ST); our secondary outcome was pharmacotherapy class received. We used logistic
      regression models to examine patient, provider, and health system factors
      associated with receiving MT or ST when compared with WW. RESULTS: There were
      393,901 incident cases of LUTD, of which 58.0% initially received WW, 41.8% MT,
      and 0.2% ST. Of the MT men, 79.8% received an alpha-blocker, 7.7% a 5-alpha
      reductase inhibitor, 3.3% an anticholinergic, and 7.3% combined therapy (alpha
      blocker and 5-alpha reductase inhibitor). In our regression models, we found that
      age (higher), race (white/black), income (low), region (northeast/south),
      comorbidities (greater), prostate-specific antigen (lower), and provider
      (nonurologist) were associated with an increased odds of receiving MT. We found
      that age (higher), race (white), income (low), region (northeast/south), initial
      provider (urologist), and prostate-specific antigen (higher) increased the odds
      of receiving ST. CONCLUSION: Most men with newly diagnosed LUTD in the Veteran's
      Health Administration receive WW, and initial surgical treatment is rare. A large
      number of men receiving MT were treated with monotherapy, despite evidence that
      combination therapy is potentially more effective in the long-term, suggesting
      opportunities for improvement in initial LUTD management within this population.

PMID- 24286605
TI  - Diabetes insipidus.
AB  - Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3
      liters/24 hours in adults and persisting even during water deprivation. It is
      mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other
      causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary
      polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A
      thorough medical history is warranted to investigate nocturnal persistence of
      polyuria (night waking being a good sign of its organic nature) to specify the
      onset and duration of the trouble, the medication use and the potential
      hereditary nature of the disorder. The next step is based on weight and blood
      pressure measurements and especially the quantification of beverages and diuresis
      over a 24-hour cycle. Assessment of signs of dehydration, bladder distention,
      pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome,
      granulomatosis and cancer is required. The diagnosis is based on biological
      assessment, pituitary magnetic resonance imaging (MRI) and results of a
      desmopressin test. In severe forms of DI, urine osmolality remains below 250
      mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine
      osmolality between 250 and 750), the water deprivation test demonstrating the
      incapacity to obtain a maximal urine concentration is valuable, together with
      vasopressin or copeptin measurement. The pituitary MRI is done to investigate the
      lack of spontaneous hyperintensity signal in the posterior pituitary, which marks
      the absence of AVP and supports the diagnosis of central DI rather than primary
      polydipsia (although not absolute); it can also recognize lesions of the
      pituitary gland or pituitary stalk. Acquired central DI of sudden onset should
      suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years,
      and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to
      hypopituitarism, including DI in 2% of cases. Transient or permanent DI is
      present in 8-9% of endoscopic transphenoidal surgeries. Current advances in DI
      concern the etiological work-up, with in particular the identification of IgG4
      related hypophysitis or many genetic abnormalities, opening the field of targeted
      therapies in the years to come.

PMID- 24286606
TI  - Rapid identification of Salmonella using Hektoen enteric agar and 16s ribosomal
      DNA probe-gold nanoparticle immunochromatography assay in clinical faecal
      specimens.
AB  - A rapid identification of Salmonella, one of the most common foodborne pathogens
      worldwide, in clinical patients can enable better rational managements and
      prevent further outbreaks. The traditional immunochromatography using antibody
      gold nanoparticles (Ab-AuNPs), such as the home pregnancy test, has been used for
      the Salmonella detection. In this study, we developed a new and rapid method
      using DNA probe-AuNPs for the detection of 16s ribosomal DNA of Salmonella. To
      evaluate the proposed method in clinical specimens, we performed a clinical test
      by identifying 159 stool samples on Hektoen agar containing black or crystalloid
      colonies using the method and the VITEK 2 system for confirmation. Eighty of the
      isolates were correctly identified as Salmonella to achieve 100% sensitivity.
      Seventy-five samples were correctly identified as non-Salmonella spp., but four
      were incorrectly identified as Salmonella. The specificity was 94.93%. The assay
      time is about 30 min after the DNA purification. The time-consuming and labour
      intense biochemical tests can be replaced. We demonstrated that this assay is a
      rapid, convenient and cost-effective tool for Salmonella identification of
      clinical faecal samples, which is worth for further promotion and clinical use.
      This is the first application of using 16s ribosomal DNA probe-Au-NPs and
      immunochromatography on clinical samples. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first application of using 16s ribosomal DNA probe-gold nanoparticles
      and immunochromatography method on clinical samples with sensitivity 100% and
      specificity 94.93%. The assay time is about 30 min after the DNA purification. We
      find this assay a rapid, convenient, sensitive and inexpensive tool for
      Salmonella identification of clinical faecal samples, which is worth further
      promotion and clinical use and can replace the traditional time-consuming and
      labour-intense biochemical tests. The potential benefit of this approach is to
      develop a rapid point-of-care test that provides results while the patient is
      still at the doctors' office.

PMID- 24286607
TI  - Can osteoarthritis be treated with light?
AB  - Osteoarthritis is becoming more problematic as the population ages. Recent
      reports suggest that the benefit of anti-inflammatory drugs is unimpressive and
      the incidence of side effects is worrying. Low-level laser (light) therapy (LLLT)
      is an alternative approach with no known side effects and with reports of
      substantial therapeutic efficacy in osteoarthritis. In this issue of Arthritis
      Research & Therapy, Alves and colleagues used a rat model of osteoarthritis
      produced by intra-articular injection of the cartilage-degrading enzyme papain to
      test 810-nm LLLT. A single application of LLLT produced significant reductions in
      inflammatory cell infiltration and inflammatory cytokines 24 hours later. A lower
      laser power was more effective than a higher laser power. However, more work is
      necessary before the title question can be answered in the affirmative. 

PMID- 24286608
TI  - Characterization and high cross-species transferability of microsatellite markers
      from the floral transcriptome of Aspidistra saxicola (Asparagaceae).
AB  - Recent studies utilizing transcriptome sequences generated by next-generation
      sequencing (NGS) technologies have demonstrated the ability to rapidly detect and
      characterize thousands of gene-based microsatellites from different plants.
      However, these simple sequence repeats (SSRs) were seldom used directly to test
      interspecific transferability in the populations of closely related species.
      Aspidistra Ker-Gawl. is a monocot genus with high species richness and diversity
      in flower structure, but its fresh floral materials are not easy to obtain. Until
      now, little is known about genetic background in the species of Aspidistra, quite
      apart from the fearful reduction of their natural habitats. In this study, the
      floral transcriptome of Aspidistra saxicola was obtained using NGS. Based on
      these data, a total of 5527 SSRs were identified in the unigenes. Among these
      SSRs, the proportions of di- and tri-nucleotide repeats were quite close (49.6%
      verse 46.8%), and the most tri-nucleotide repeats were AGG/CCT followed by
      AAG/CTT and AGC/GCT in A. saxicola, showing distinct differences with other
      angiosperm species. To assess genetic diversity in the species of Aspidistra, 48
      SSR loci were tested in four available populations of A. elatior. The results
      revealed that more than a third of the loci were polymorphic. The majority of
      these primers could be amplified in 24 species representing the main clades of
      Aspidistra. The primer subsets from transcriptome data proved highly useful for
      detecting polymorphisms in the related species, supporting the finding that NGS
      is an efficient approach to molecular marker development at both intra- and
      interspecies levels, especially in endangered nonmodel species.

PMID- 24286609
TI  - Relationship between clinical features and inflammation-related monocyte gene
      expression in bipolar disorder - towards a better understanding of
      psychoimmunological interactions.
AB  - OBJECTIVES: Existing and previously published datasets were examined for
      associations between illness and treatment characteristics and monocyte pro
      inflammatory gene expression in patients with bipolar disorder (BD). We
      hypothesized a priori that increased monocyte pro-inflammatory gene expression
      would be found more frequently in patients with a lifetime history of psychotic
      symptoms. METHODS: Monocyte quantitative polymerase chain reaction and symptom
      data from 64 patients with BD were collected from three Dutch studies. Regression
      analyses were performed to analyze the various associations between pro
      inflammatory gene expression and clinical features, from which feature-expression
      heat maps were drawn. RESULTS: No associations were found between pro
      inflammatory gene expression and lifetime psychotic symptoms, whereas a positive
      association was identified between subcluster 2 genes and manic symptoms. For
      several subcluster 1a genes, a negative association was found with age at onset.
      For most subcluster 2 genes, a positive association was found with the duration
      of illness. Current use of antidepressants and of anti-epileptic agents was
      associated with subcluster 2 gene expression, and current use of lithium and
      antipsychotic agents with subcluster 1a gene expression. CONCLUSIONS: Our
      hypothesis that lifetime psychotic features would be associated with pro
      inflammatory monocyte gene expression was not confirmed. In an explorative
      analysis we found: (i) a possible relationship between pro-inflammatory gene
      expression and manic symptomatology; (ii) a differential immune activation
      related to age at onset and duration of illness; and (iii) support for the
      concept of an immune suppressive action of some of the mood-regulating
      medications.

PMID- 24286611
TI  - Hospital management and clinical factors associated with ophthalmic involvement
      in toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic Epidermal Necrolysis (TEN) is characterized by an exfoliative
      rash resembling widespread burns. It is often considered on the same spectrum of
      disease as Stevens Johnson Syndrome but is distinguished by epidermal detachment
      of >30% of total body surface area (TBSA). Ocular involvement of TEN may result
      in complications requiring intensive topical, systemic or operative treatment.
      This study aimed to identify the current hospital management of, and factors
      associated with, ophthalmic involvement in adult TEN patients. METHODS: All adult
      TEN patients admitted to the Victorian Adult Burns Service over an 12-year period
      were included. Retrospective data analyzed included patient demographics, site of
      TEN involvement, % TBSA, complications, duration of ocular follow up and visual
      outcomes. RESULTS: TEN patients with and without ocular involvement were
      compared. Cutaneous involvement of the head and neck was found to be
      significantly associated with ocular involvement of TEN. Age, TBSA involvement,
      presence of a prodrome, and presence of comorbidities were not found to be
      significantly associated with ocular involvement. Management of ophthalmic
      involvement of TEN varied between patients. CONCLUSIONS: Clinicians should have a
      high index of suspicion for ocular involvement when exfoliation of the head and
      neck is present and should seek ophthalmological advice early in the course of
      disease.

PMID- 24286610
TI  - The Francisella O-antigen mediates survival in the macrophage cytosol via
      autophagy avoidance.
AB  - Autophagy is a key innate immune response to intracellular parasites that
      promotes their delivery to degradative lysosomes following detection in the
      cytosol or within damaged vacuoles. Like Listeria and Shigella, which use
      specific mechanisms to avoid autophagic detection and capture, the bacterial
      pathogen Francisella tularensis proliferates within the cytosol of macrophages
      without demonstrable control by autophagy. To examine how Francisella evades
      autophagy, we screened a library of F. tularensis subsp. tularensis Schu S4
      HimarFT transposon mutants in GFP-LC3-expressing murine macrophages by microscopy
      for clones localized within autophagic vacuoles after phagosomal escape. Eleven
      clones showed autophagic capture at 6 h post-infection, whose HimarFT insertions
      clustered to fourgenetic loci involved in lipopolysaccharidic and capsular O
      antigen biosynthesis. Consistent with the HimarFT mutants, in-frame deletion
      mutants of two representative loci, FTT1236 and FTT1448c (manC), lacking both LPS
      and capsular O-antigen, underwent phagosomal escape but were cleared from the
      host cytosol. Unlike wild-type Francisella, the O-antigen deletion mutants were
      ubiquitinated, and recruited the autophagy adaptor p62/SQSTM1 and LC3 prior to
      cytosolic clearance. Autophagy-deficient macrophages partially supported
      replication of both mutants, indicating that O-antigen-lacking Francisella are
      controlled by autophagy. These data demonstrate the intracellular protective role
      of this bacterial surface polysaccharide against autophagy. 

PMID- 24286612
TI  - Insurance coverage of pediatric burns: Switzerland versus USA.
AB  - Burn care and research have significantly improved over the past years. However,
      insurance coverage of such treatments does not reflect the improvements in this
      multi-disciplinary field. Government insurance policies in first world countries
      renown for burn care treatment, such as Switzerland and the United States, have
      not adapted to the complexity and longitudinal nature of burn care. Using case
      studies from both countries, we have analyzed both the institutional and policy
      approach to pediatric burn treatment coverage. Subsequently, by presenting the
      Shriners burn care model, we offer a policy recommendation to both the Swiss and
      the American governments to better their present legislation and infrastructure
      on pediatric burn coverage. 

PMID- 24286613
TI  - Coming to terms with it all: adult burn survivors' 'lived experience' of
      acknowledgement and acceptance during rehabilitation.
AB  - Although studies have explored the 'lived experience' of burn survivors, little
      is known about their experiences encountered during rehabilitation. A descriptive
      phenomenological study was conducted to gain an in-depth insight into burn
      survivors' experiences' of acknowledgement and acceptance of their injury and the
      challenges experienced during their rehabilitation journey. A descriptive
      phenomenological methodology was used to construct themes depicting how burn
      survivors endeavoured to acknowledge and accept their injury and subsequent
      altered body image. Twenty men and one woman up to eight years after-burn within
      Australia were selected through purposeful sampling, and data were collected
      through in-depth individual interviews conducted in 2011 (N = 21). Interviews
      were analysed using Colaizzi's method of data analysis. The emergent theme
      acknowledgement identified four cluster themes that represented how burn
      survivors came to terms with their injury and an altered body image: (1)
      reasoning (2) humour (3) the challenge of acceptance (4) self-awareness. Coming
      to terms with a severe burn is a challenging experience. Reasoning and humour are
      strategies utilised by burn survivors that facilitate with acknowledgement and
      acceptance. Understanding these concepts through the burn survivors' perspective
      will, potentially, facilitate a better understanding of how to best provide for
      this cohort of patients.

PMID- 24286614
TI  - Association of breast vascular calcifications with low bone mass in
      postmenopausal women.
AB  - BACKGROUND: In developing countries, there is a deficiency of densitometers with
      which to screen the population for osteoporosis. Thus, strategies with which to
      select patients for a bone density test are desirable. OBJECTIVE: To determine
      whether breast vascular calcifications (BVCs) may be employed to identify
      postmenopausal women with osteoporosis/osteopenia. METHODS: This was a cross
      sectional study of postmenopausal women subjected to bilateral mammography and
      bone densitometry (DXA) of the spine and hip. A medical interview registered
      possible confounding factors, such as age, length of menopause, previous use of
      postmenopausal hormone therapy, family history of osteoporosis, smoking,
      alcoholism, hypertension, diabetes, cardiovascular diseases, and medication use.
      RESULTS: The study included 211 postmenopausal women aged 62.1 +/- 9.3 years, 38
      of whom (18.0%) exhibited BVC. Osteoporosis was detected in 36 (17.1%), and a T
      score < 21.0 for any site was found in 164 (77.7%). No statistically significant
      difference was found between the groups without BVC (n = 173) and with BVC (n =
      38) for the prevalence of 'osteoporosis' or 'moderate/severe osteopenia or
      osteoporosis' at the spine or at any other site. There was a difference between
      the groups in terms of age (59.0 +/- 7.8 vs. 71.9 +/- 8.9 years, respectively; p
      < 0.001), sedentary lifestyle (57.8% vs. 84.2%, respectively; p = 0.002), smoking
      (27.7% vs. 7.9%, respectively; p = 0.009), and high blood pressure (65.3% vs.
      92.1%, respectively; p = 0.001). Logistic regression analysis confirmed the lack
      of statistical significance for BVC as a predictor of an osteoporosis diagnosis.
      Sensitivity values of BVCs to detect osteoporosis or osteopenia ranged from 17.9%
      to 25.0%. CONCLUSION: BVCs have been shown to be inadequate to identify
      postmenopausal women with osteoporosis or osteopenia.

PMID- 24286615
TI  - Does the rectus femoris nerve block improve knee recurvatum in adult stroke
      patients? A kinematic and electromyographic study.
AB  - Knee recurvatum (KR) during gait is common in hemiplegic patients. Quadriceps
      spasticity has been postulated as a cause of KR in this population. The aim of
      this study was to assess the role of rectus femoris spasticity in KR by using
      selective motor nerve blocks of the rectus femoris nerve in hemiparetic stroke
      patients. The data from six adult, post-stroke hemiplegic patients who underwent
      a rectus femoris nerve block for a stiff-knee gait were retrospectively analyzed.
      An extensive clinical and functional evaluation was performed and gait was
      assessed by motion analysis (kinematic, kinetic and electromyographic parameters)
      before and during the block realized using 2% lidocaine injected under a
      neurostimulation and ultrasonographic targeting procedure. The main outcome
      measures were the peak knee extension in stance and peak knee extensor moment
      obtained during gait analysis. No serious adverse effect of the nerve block was
      observed. The block allowed a reduction of rectus femoris overactivity in all
      patients. Peak knee extension and extensor moment in stance did not improve in
      any patient, but peak knee flexion during the swing phase was significantly
      higher after block (mean: 31.2 degrees  post, 26.4 pre, p < 0.05). Our results
      provide arguments against the hypothesis that the spasticity of the rectus
      femoris contributes to KR.

PMID- 24286616
TI  - Detection and differentiation of causative organisms of onychomycosis in an ex
      vivo nail model by means of Raman spectroscopy.
AB  - BACKGROUND: Onychomycosis is worldwide the most prevalent infection of the nail.
      It is mainly caused by the dermatophytes Trichophyton rubrum and Trichophyton
      mentagrophytes and to a lesser extent Trichophyton tonsurans. The yeast Candida
      albicans and the mould Scopulariopsis brevicaulis can also cause onychomycosis.
      Management of these nail conditions may require appropriate treatment methods and
      therefore the identification of the causative species can be of importance.
      However, the determination of agents causing onychomycosis is still not optimal.
      OBJECTIVES: To detect and differentiate causative organisms of onychomycosis in
      an ex vivo nail model by means of Raman spectroscopy. The work focusses is on the
      discriminative power of Raman spectroscopy for detection of differences between
      T. rubrum, T. mentagrophytus and T. tonsurans on human nail and distinguishing
      these dermatophytic from the non-dermatophytic species S. brevicaulis and C.
      albicans. METHODS: Raman spectra (200/sample) were taken from 50-MUm human nail
      slices infected with T. rubrum, T. mentagrophytus, T. tonsurans, S. brevicaulis
      or C. albicans using a 2500 High-Performance Raman Module and 785-nm diode laser.
      Processed spectra were analysed by sorting the correlation matrix and presented
      as dendrogram and heat map. Raman spectra from suspended dermatophytic
      microconidia were taken for mutual comparisons. RESULTS: Spectral differences
      between the dermatophytes T. rubrum, T. mentagrophytus and T. tonsurans (635-795,
      840-894, 1018-1112, 1206-1372, 1566-1700/cm) and the non-dermatophytes S.
      brevicaulis and C. albicans (442-610, 692-758, 866-914, 1020-1100, 1138-1380,1492
      1602/cm) growing on nail were confirmed by clustering correlation showing two
      main clusters. Dissimilarities between tested dermatophytes were also found with
      T. rubrum being most different. Raman spectra of the dermatophytic microconidia
      varied over the whole tested 400-1800/cm range. CONCLUSION: Important
      dermatophytic and non-dermatophytic agents of onychomycosis growing on ex vivo
      human nail can be distinguished specifically and non-invasively by Raman
      spectroscopy.

PMID- 24286617
TI  - Reduced E-cadherin expression is associated with abdominal pain and symptom
      duration in a study of alternating and diarrhea predominant IBS.
AB  - BACKGROUND: Increased intestinal permeability and altered expression of tight
      junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel
      syndrome (IBS). This study aimed to investigate the expression of adherens
      junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and
      claudin (CLD)-1 and associations with IBS symptoms. METHODS: Junctional proteins
      were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34)
      comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes,
      and controls (n = 12). IBS symptom duration, abdominal pain severity and stool
      frequency were assessed for IBS patients. Protein expression was determined by
      immunofluorescence. KEY RESULTS: E-cadherin and ZO-1 protein expression was
      significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface
      epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1
      expression was not significantly altered compared with controls. On subtype
      analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D
      compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E
      cadherin expression was associated with longer symptoms duration specifically in
      IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with
      abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but
      this association was unrelated to IBS subtype. CONCLUSIONS & INFERENCES: E
      cadherin protein expression in the cecum was significantly lower in IBS-A
      compared with controls and associated with longstanding symptoms. E-cadherin was
      further associated with abdominal pain severity in the IBS group overall, but
      unrelated to IBS subtype. Altered E-cadherin expression may provide novel
      insights into mechanisms underlying intestinal barrier dysfunction in IBS.

PMID- 24286618
TI  - Folate deficiency in Crohn's disease.
AB  - There are several causes for folate deficiency in Crohn's disease: malnutrition,
      malabsorption, excess folate utilization and medications. A combination of these
      factors may be responsible for the deficiency of this vitamin in some cases.

PMID- 24286619
TI  - Transcriptional regulation of human USP24 gene expression by NF-kappa B.
AB  - Impairment of the ubiquitin proteasome pathway is believed to play an important
      role in the pathogenesis of Parkinson's disease. This process is carried out
      under tight regulation by deubiquitinating enzymes. Genetic linkage studies
      indicated that the region of the human ubiquitin-specific protease 24 (USP24)
      gene is significantly correlated with Parkinson's disease. In this study, we
      cloned a 1648 bp 5' flanking region of the human USP24 gene coding sequence and a
      series of nested deletions into the pGL3-Basic vector. We analyzed promoter
      activities of these regions with a luciferase-based reporter assay system. A 64
      bp region was identified to contain the transcription initiation site and a
      minimum promoter sequence for transcriptional activation of the USP24 gene
      expression. Expression of USP24 is controlled by a TATA-box-less promoter with
      several putative cis-acting elements. Transcriptional activation and gel-shift
      assay demonstrated that the USP24 gene promoter contains a functional NFkappaB
      binding site. Over-expression of nuclear factor kappa-light-chain-enhancer of
      activated B cells (NFkappaB) and tumor-necrosis factor alpha (TNFalpha) treatment
      significantly increased the USP24 promoter activity, mRNA expression and protein
      level in human HEK293 cells, mouse N2a cells and human neuroblastoma SH-SY5Y
      cells. Deletion and mutation of the binding site abolished the regulatory effect
      of NFkappaB on human USP24 gene transcription. These results suggested that USP24
      expression is tightly regulated at its transcription level and NFkappaB plays an
      important role in this process.

PMID- 24286620
TI  - Uptitration of renin-angiotensin system blocker and beta-blocker therapy in
      patients hospitalized for heart failure with reduced versus preserved left
      ventricular ejection fractions.
AB  - In ambulatory patients with heart failure (HF) and reduced ejection fraction
      (rEF), renin-angiotensin system (RAS) and beta-blockers at guideline-recommended
      target dose reduce all-cause mortality and readmissions. Benefits in HF with
      preserved ejection fraction (pEF), as well as uptitration after a
      hospitalization, remain uncertain. This study assesses the impact of RAS- and
      beta-blocker uptitrations in patients with HFrEF versus HFpEF during and
      immediately after a hospital admission. In consecutive patients (209 HFrEF with
      left ventricular ejection fraction <40% and 108 HFpEF with left ventricular
      ejection fraction >=40%), RAS- and beta-blocker dose changes were followed during
      6 months after an index HF hospitalization. Patients with a RAS- and beta-blocker
      dose increase of >=10% of the recommended target dose were compared with patients
      without uptitration. Patients who received uptitration were significantly
      younger, with a higher heart rate and better renal function, and received
      spironolactone more often. Both RAS- and beta-blocker uptitrations were
      associated with significant reductions in the composite end-point of all-cause
      mortality or HF readmissions in HFrEF (hazard ratio [HR] 0.36, 95% confidence
      interval [CI] 0.22 to 0.60 and HR 0.51, 95% CI 0.32 to 0.81, respectively). After
      correction for age, heart rate, blood pressure, renal function, and
      spironolactone use, this association remained significant for RAS blockers (HR
      0.54, 95% CI 0.31 to 0.93, p = 0.027) but not for beta-blockers (HR 0.65, 95% CI
      0.39 to 1.09, p = 0.101). No benefit of RAS- or beta-blocker uptitration was
      observed in HFpEF. In conclusion, uptitration of neurohumoral blockers after an
      HF hospitalization is more frequently performed in younger patients with low co
      morbidity burden. RAS-blocker uptitration independently predicts clinical outcome
      in patients with HFrEF but not in those with HFpEF. 

PMID- 24286621
TI  - Remote ischemic conditioning for patients with heart failure?

PMID- 24286622
TI  - High-sensitivity troponin T is more susceptible than high-sensitivity troponin I
      to impaired renal function.

PMID- 24286623
TI  - Thiamin-dependent enzymes: new perspectives from the interface between chemistry
      and biology.
AB  - Identification and enzymological study of the multitude of thiamin (vitamin B1)
      dependent enzymes open new ways to investigate metabolic regulation and disease
      treatments. The significant contribution of enzymes employing thiamin diphosphate
      as a coenzyme to solving medical and biotechnological problems is highlighted,
      together with the currently underestimated role of the enzymes in controlling the
      levels of the non-coenzyme thiamin derivatives. 

PMID- 24286624
TI  - Effects of culture conditions on spore types of Clonostachys rosea 67-1 in
      submerged fermentation.
AB  - The promising biocontrol isolate Clonostachys rosea 67-1 was investigated to
      clarify the effects of culture conditions on chlamydospore production in
      submerged fermentation. Culture conditions significantly affected both
      performance and types of C. rosea sporulation. C. rosea 67-1 was hard to generate
      chlamydospores under conventional conditions. However, the proportion of
      resistant spores increased to 17.4 and 15.5% in PD and rice meal media,
      respectively, in 8 days. Chlamydospore productivity was boosted (>threefold) with
      the addition of 50-200 mg l(-1) CuSO4 . The pH of the medium played a vital role
      in 67-1 sporulation. The percentage of chlamydospores decreased rapidly with
      increased pH (88.1% at pH 3.0 to 1.0% at pH 6.5). The optimal pH for conidia
      production was 6.0-6.5, at which chlamydospore forming was strongly inhibited.
      Regulating pH during fermentation contributed to improving output and proportion
      of resistant spores. When 67-1 was inoculated into broth with an initial pH of
      6.5, followed by adjustment to pH 3.5 after 48 h, the number of chlamydospores
      reached 1.1 * 10(8) ml(-1). The impact of temperature and rotational speed was
      also analysed; an ultimate capacity of chlamydospores was achieved at 30 degrees
      C and the speed above 120 rev min(-1) (P < 0.05). SIGNIFICANCE AND IMPACT OF THE
      STUDY: Clonostachys rosea is one of the most promising biocontrol agents in
      countering many plant fungal diseases. However, large-scale production and
      commercialization are hampered by the lack of understanding of the impacts of
      culture conditions on performance and types of C. rosea sporulation and
      subsequently inadequate research on the techniques for chlamydospore production.
      In addressing these concerns, this study provides a unique insight into the
      manipulation of C. rosea sporulation and chlamydospore fermentation of the
      biocontrol fungus.

PMID- 24286625
TI  - Evaluation of the EasyScreenTM enteric parasite detection kit for the detection
      of Blastocystis spp., Cryptosporidium spp., Dientamoeba fragilis, Entamoeba
      complex, and Giardia intestinalis from clinical stool samples.
AB  - The aim of this study was to evaluate the EasyScreenTM Enteric Parasite Detection
      Kit (Genetic Signatures, Sydney, Australia) for the detection and identification
      of 5 common enteric parasites: Blastocystis spp., Cryptosporidium spp.,
      Dientamoeba fragilis, Entamoeba complex, and Giardia intestinalis in human
      clinical samples. A total of 358 faecal samples were included in the study. When
      compared to real-time PCR and microscopy, the EasyScreenTM Enteric Parasite
      Detection Kit exhibited 92-100% sensitivity and 100% specificity and detected all
      commonly found genotypes and subtypes of clinically important human parasites. No
      cross reactivity was detected in stool samples containing various other
      bacterial, viral, and/or protozoan species. The EasyScreenTM PCR assay was able
      to provide rapid, sensitive, and specific simultaneous detection and
      identification of the 5 most important diarrhoea-causing enteric parasites that
      infect humans. It should be noted, however, that the EasyScreenTM Kit does not
      substitute for microscopy or for additional PCRs as it does not detect the
      pathogenic Coccidia spp. Cystoisospora belli or Cyclospora cayetanensis and it
      does not differentiate between pathogenic and nonpathogenic Entamoeba spp. This
      study also highlights the lack of sensitivity demonstrated by microscopy; as
      such, molecular methods should be considered the diagnostic method of choice for
      enteric parasites. 

PMID- 24286626
TI  - Effect of variations to a simulated system of straw phonation therapy on
      aerodynamic parameters using excised canine larynges.
AB  - OBJECTIVES/HYPOTHESIS: Resonance tubes are commonly used in voice therapy. These
      devices modify supraglottal impedance, potentially decreasing the aerodynamic
      power necessary for phonation. We modeled phonation with resonance tubes in
      excised larynges and evaluated the effects of varying tube width, tube length,
      and flow input on phonation threshold pressure (PTP) and phonation threshold flow
      (PTF). We hypothesized that the increased vocal economy observed in human
      subjects and several other models would be observed in excised larynges. STUDY
      DESIGN: Repeated measures excised canine larynx bench experiment with each larynx
      serving as own control. METHODS: Nine conditions were evaluated, namely control,
      two tube diameters (17.5 and 6.5mm), three tube lengths (7.8, 15.0, and 30.0cm),
      and three levels of flow input (80, 114, and 200mL/s). Aerodynamic data were
      collected for 11 excised canine larynges attached to an artificial vocal tract,
      and results from each experimental configuration were compared with control.
      RESULTS: A significant decrease in average PTP occurred compared with control for
      the 114- and 200-mL/s flow inputs, 30-cm extension, and 17.5- and 6.5-mm
      constrictions. Average PTF decreased compared with control for every
      configuration, although statistically significant changes were only observed for
      200-mL/s flow and 6.5-mm constriction. CONCLUSIONS: Knowledge regarding the
      effect of vocal tract alterations could be clinically useful in determining the
      optimal "straw" configuration for voice therapy. Further exploration of the
      relationships among width, length, and flow input could provide theoretical
      support for the development of new therapies and resonance tube devices.

PMID- 24286627
TI  - Systemic sclerosis, birth order and parity.
AB  - AIM: A recent study identified increasing birth order to be a risk factor for the
      development of systemic sclerosis (SSc). This finding supports the theory that
      transplacental microchimerism may be a key pathological event in the initiation
      of SSc. We investigated the relationship between birth order and parity and the
      age of onset of SSc in South Australia. METHOD: A retrospective analysis of
      patient data in the South Australian Scleroderma Register was performed. Data
      were obtained from a mailed questionnaire. Control data was collected
      prospectively using a similar questionnaire. The relationship between birth
      order, family size or parity and risk of subsequent development of SSc was
      analyzed by mixed effects logistic regression analysis. RESULTS: Three hundred
      and eighty-seven index probands were identified and compared with 457 controls.
      Controls were well matched for gender, but not for age. No statistically
      significant relationship was identified between SSc and birth order, parity in
      females, family size, age at first pregnancy in females or gender of first child
      in parous females. CONCLUSION: Our data suggests that parity, age at first
      pregnancy and the gender of the first child are not relevant factors in our
      understanding of the epidemiology and pathogenesis of SSc. Birth order and family
      size in both genders also appears irrelevant. These results argue against
      microchimerism as being relevant in the pathogenesis of SSc and add further
      support to the theory that stochastic events may be important in the
      etiopathogenesis of SSc.

PMID- 24286628
TI  - Detrimental effects of acute hyperglycaemia on the rat heart.
AB  - AIM: Hyperglycaemia is an important risk factor for acute myocardial infarction.
      It can lead to increased induction of non-oxidative glucose pathways (NOGPs) -
      polyol and hexosamine biosynthetic pathways, advanced glycation end products and
      protein kinase C - that may contribute to cardiovascular diseases onset. However,
      the precise underlying mechanisms remain poorly understood. Here we hypothesized
      that acute hyperglycaemia increases myocardial oxidative stress and NOGP
      activation resulting in cardiac dysfunction during ischaemia-reperfusion and that
      inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT)
      treatment], leads to cardioprotection. METHODS: We employed several experimental
      systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit
      buffer containing 33 mm glucose vs. controls (11 mm glucose) +/- global ischaemia
      and reperfusion +/- BFT (first 20 min of reperfusion); (ii) Infarct size
      determination as per the ischaemic protocol, but with regional ischaemia and
      reperfusion +/- BFT treatment; in separate experiments, NOGP inhibitors were also
      employed for (i) and (ii); and (iii) In vivo coronary ligations performed on
      streptozotocin-treated rats +/- BFT treatment (early reperfusion). RESULTS: Acute
      hyperglycaemia generated myocardial oxidative stress, NOGP activation and
      apoptosis, but caused no impairment of cardiac function during pre-ischaemia,
      thereby priming hearts for later damage. Following ischaemia-reperfusion (under
      hyperglycaemic conditions), such effects were exacerbated together with cardiac
      contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting
      away by BFT treatment (in part) improved cardiac function during ischaemia
      reperfusion. CONCLUSION: Coordinate NOGP activation in response to acute
      hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion,
      allowing for the development of novel cardioprotective agents.

PMID- 24286629
TI  - Could comorbid bipolar disorder account for a significant share of executive
      function deficits in adults with attention-deficit hyperactivity disorder?
AB  - OBJECTIVE: The frequent comorbidity between attention-deficit hyperactivity
      disorder (ADHD) and bipolar disorder (BD) represents a challenge for
      disentangling specific impairments of each disorder in adulthood. Their
      functional impairments seem to be mediated by executive function deficits.
      However, little is known about the extent to which each executive function
      deficit might be disorder specific or explained by the comorbidity. The aim of
      the present study was to determine if comorbid BD could account for a significant
      share of executive function deficits when measured by the Wisconsin Card Sorting
      Test (WCST) in adults with ADHD. METHODS: Adult patients with ADHD and healthy
      subjects were evaluated in the ADHD outpatient Program at the Hospital de
      Clinicas de Porto Alegre. Psychiatric diagnoses were based on DSM-IV criteria.
      WCST scores were compared by multivariate analysis of covariance among three
      groups: ADHD with BD (n = 51), ADHD without BD (n = 278), and healthy subjects (n
      = 91). RESULTS: When compared to patients without BD and healthy subjects,
      patients with ADHD and comorbid BD showed lower scores in total correct answers
      (p = 0.003); higher scores in total errors (p = 0.004) and non-perseverative
      errors (p = 0.002); and completed fewer categories (p = 0.009). Patients with
      ADHD without BD did not differ from healthy subjects. CONCLUSIONS: WCST
      impairments among patients with ADHD seem to be to a large extent attributable to
      comorbid BD. Although other executive function deficits (e.g., in the inhibitory
      control domain) have been demonstrated to accompany ADHD, the present findings
      suggest that set-shifting deficits are strongly related to comorbid BD.

PMID- 24286630
TI  - The broad bacterial blight resistance of rice line CBB23 is triggered by a novel
      transcription activator-like (TAL) effector of Xanthomonas oryzae pv. oryzae.
AB  - Bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is not only
      a disease devastating rice production worldwide, but also an ideal model system
      for the study of the interaction between plants and their bacterial pathogens.
      The rice near-isogenic line (NIL) CBB23, derived from a cross between a wild rice
      Oryza rufipogon accession (RBB16) and a susceptible indica rice variety (Jingang
      30), is highly resistant to all field Xoo strains tested so far. Although the BB
      resistance of CBB23 has been widely used in rice breeding programmes, the
      mechanism of its extremely broad-spectrum resistance remains unknown. Here, we
      report the molecular cloning of an avirulence gene, designated as avrXa23, from
      Xoo strain PXO99(A) . We validate that AvrXa23, a novel transcription activator
      like effector, specifically triggers the broad-spectrum BB resistance in CBB23.
      The prevalence of avrXa23 in all 38 Xoo strains surveyed may explain the broad
      spectrum feature of BB resistance in CBB23. The results will significantly
      facilitate the molecular cloning of the corresponding resistance (R) gene in the
      host, and provide new insights into our understanding of the molecular mechanism
      for broad-spectrum disease resistance in plants. 

PMID- 24286632
TI  - Could safety boards provide a valuable tool to enhance the safety of reproductive
      medicine?
AB  - Medicine and aviation have a striking number of similarities. Both are led by
      highly-trained individuals performing complex tasks that are critical to
      outcomes. They also integrate the efforts of other professionals to assure that
      the flight, procedures, or processes are completed successfully. Also in common,
      is the potential for errors to have catastrophic and even life-threatening
      consequences. Both aviation and medicine have responded to this complex operating
      environment by building safety programs. Unfortunately, those in medicine have
      not been optimal in reducing significant adverse outcomes, including deaths. It
      has been suggested that given the parallels, that aviation safety programs might
      be adapted to clinical medicine. One such measure would the formation of a
      Clinical Safety Board (CSB) modeled after the National Transportation Safety
      Board (NTSB). Such a board would collect data across the nation and determine
      root causes of errors. They may then provide recommendations to professional
      societies and regulatory agencies for consideration for implementation. Such
      programs would be dependent on accurate and thorough reporting. Indemnification,
      similar to that enacted by the federal government for aviation, would be
      critical. In the end, a CSB should empower better patient care with reduced
      liability to the providers and programs. 

PMID- 24286633
TI  - President's Page: New ACC/AHA prevention guidelines: building a bridge to even
      stronger guideline collaborations.

PMID- 24286634
TI  - EURECCA consensus conference highlights about rectal cancer clinical management:
      the radiation oncologist's expert review.
AB  - BACKGROUND AND PURPOSE: Although rectal and colon cancer management has
      progressed greatly in the last few decades clinical outcomes still need to be
      optimized. Furthermore, consensus is required on several issues as some of the
      main international guidelines provide different recommendations. The European
      Registration of Cancer Care (EURECCA) drew up documents to standardize management
      and care in Europe and aid in decision-making. MATERIAL AND METHODS: In the
      present section the panel of experts reviews and discusses data from the
      literature on rectal cancer, focusing on recommendations for selecting between
      short-course radiotherapy (SCRT) and long-course radio-chemotherapy (LCRTCT) as
      preoperative treatment as well as on the controversies about adjuvant treatment
      in patients who had received a pre-operative treatment. RESULTS: The starting
      point of the present EURECCA document is that adding SCRT or LCRTCT to TME
      improved loco-regional control but did not increase overall survival in any
      single trial which, in any case, had improved with the introduction of total
      mesorectal excision (TME) into clinical practice. Moderate consensus was achieved
      for cT3 anyNM0 disease. In this frame, agreement was reached on either SCRT
      followed by immediate surgery or LCRTCT with delayed surgery for mesorectal
      fascia (MRF) negative tumors at presentation. LCRTCT was recommended for tumor
      shrinkage in MRF+ at presentations but if patients were not candidates for
      chemotherapy, SCRT with delayed surgery is an option/alternative. LCRTCT was
      recommended for cT4 anycNM0. SCRT offers the advantages of less acute toxicity
      and lower costs, and LCRTCT tumor shrinkage and down-staging, with 13-36%
      pathological complete response (pCR) rates. To improve the efficacy of
      preoperative treatment both SCRT and LCRTCT have been, or are being, associated
      with diverse schedules of chemotherapy and even new targeted therapies but
      without any definitive evidence of benefit. Nowadays, standard treatment is
      fluoropyrimidine alone since alternative agents and regimens have not been shown
      to be more active, only more toxic. CONCLUSIONS: The EURECCA panel summarized
      available evidence in an attempt to reduce variance in rectal cancer management.
      This is expected to benefit patients. Results from ongoing randomized trials will
      help clarify some of the issues that are still under debate.

PMID- 24286636
TI  - Potent vasodilatory effect of fasudil on radial artery graft in coronary artery
      bypass operations.
AB  - BACKGROUND: The radial artery (RA) is a useful conduit for coronary artery bypass
      grafting (CABG) but is susceptible to vasospasm during harvesting. We evaluated
      the usefulness of fasudil, a Rho kinase inhibitor, in dilating the RA graft and
      increasing graft free flow (GFF) compared with the conventional graft-dilating
      agents papaverine and verapamil-nitroglycerin (VG). METHODS: Between June 2012
      and January 2013, 45 patients with ischemic heart disease who underwent isolated
      CABG using the RA were enrolled and randomly assigned to fasudil (n = 15),
      papaverine (n = 15), or VG (n = 15). Fasudil (2.67 mmol/L), papaverine (1.0
      mmol/L) mixed with heparinized blood, or VG (30 MUmol/L each of verapamil and
      nitroglycerin) was injected intraluminally into the RA graft after harvesting.
      Main outcome measures were RA GFF, hemodynamic changes, and histopathologic
      examination of the RA. RESULTS: In the fasudil group, GFF increased significantly
      (p < 0.001) from 36.8 +/- 20.4 at baseline to 148.0 +/- 88.3 mL/min after
      injection. GFF increased significantly (p < 0.001) from 36.0 +/- 19.0 to 72.3 +/-
      36.7 mL/min in the papaverine group and increased significantly (p < 0.001) from
      39.5 +/- 23.3 to 64.3 +/- 29.9 mL/min in the VG group. The GFF was significantly
      higher (p = 0.001) in fasudil-treated RA than in papaverine- or VG-treated RA.
      Histopathologically, RA graft diameter was markedly increased after fasudil
      injection, and the structure of the multiple elastic lamellae was intact. Blood
      pressure did not change significantly after drug injection in all groups.
      CONCLUSIONS: Fasudil exhibited a very potent vasodilatory effect on the RA
      compared with conventional papaverine or VG, resulting in increased GFF. This
      agent is useful for dilating RA grafts in CABG.

PMID- 24286635
TI  - Survival of patients with unsuspected pN2 non-small cell lung cancer after an
      accurate preoperative mediastinal staging.
AB  - BACKGROUND: The aim of this study is to analyze the survival of patients with non
      small cell lung cancer (NSCLC) without clinical suspicion of mediastinal lymph
      node involvement who underwent complete resection and whose tumors were finally
      proven to be pathologic N2 (pN2). METHODS: This is a retrospective study of a
      prospective database from January 2004 to December 2010. A total of 621 patients
      with NSCLC were staged and operated according to the European Society of Thoracic
      Surgeons guidelines. After exclusions (previous induction treatment, carcinoid
      tumors, small cell carcinomas), 540 patients were analyzed; 406 (75%) required
      surgical exploration of the mediastinum and 134 (25%) underwent surgery directly.
      Survival analysis was performed by the Kaplan-Meier method and the log-rank test
      was used for comparisons. RESULTS: Thirty (5.5%) patients had unsuspected pN2 and
      complete resection was achieved in 27 (90%). Three- and 5-year survival rates
      were 87% and 81%, respectively, for patients with a true negative result of the
      protocol (pN0-1), and 79% and 40%, respectively, for those with a false negative
      result (unsuspected pN2) (p < 0.0001). CONCLUSIONS: The rate of unsuspected pN2
      in patients whose tumors were staged according to the European Society of
      Thoracic Surgeons guidelines was low. The survival of this group of patients was
      better than expected. Therefore, resection of properly staged unsuspected pN2
      NSCLC is reasonable and should not be avoided if complete resection can be
      achieved.

PMID- 24286637
TI  - Flapless implant surgery to overcome anatomic challenges in the anterior mandible
      for overdenture therapy: a clinical report.
AB  - Implant surgery in the atrophic anterior mandible presents a number of anatomic
      challenges owing to the vascular and neurologic structures related to this
      region. Flapless implant surgery is known to be a conservative surgical approach
      that has a number of advantages and disadvantages for both the clinician and the
      patient. This clinical report describes the use of flapless implant surgery for a
      2-implant overdenture in an 89-year-old patient with a severely atrophic mandible
      and significant anatomic constraints. The insertion of the sublingual artery into
      the lingual cortex close to the level of the crest of the ridge and the presence
      of the mental foramen at the ridge crest precluded conventional flap surgery. To
      overcome these anatomic challenges, a conventional surgical guide was used with
      careful preoperative treatment planning for a successful flapless implant surgery
      and subsequent overdenture therapy. The anatomic challenges, surgical and
      prosthetic treatment planning, choice of simple versus complex interventions, and
      indications and contraindications of flapless surgery are discussed. 

PMID- 24286638
TI  - Assessing the accuracy of computer color matching with a new dental porcelain
      shade system.
AB  - STATEMENT OF PROBLEM: In a previous study, a novel computer color matching system
      for dental ceramic restoration was developed, and 21 new shades were established.
      Theoretically, a natural tooth color can be accurately reproduced by combining 2
      or 3 ceramic mixtures from the database of 21 new shades. PURPOSE: The purpose of
      this study was to test the use of these shades in conjunction with the computer
      color matching system to determine their ability to accurately reproduce the body
      color of 29 shade tabs from a shade guide (VITAPAN 3D-Master). MATERIAL AND
      METHODS: Disks of 21 reference shades were prepared with porcelain (Cerabien CZR)
      and polished to 1.0 mm thickness. A spectrophotometer was used to measure the
      reflectance values from 380 to 780 nm for each disk; the scattering coefficient
      and absorption coefficient were determined. By using the reflectance values and
      the scattering and absorption coefficients, the computer color matching program
      generated porcelain prescriptions incorporating proportions from the 21 reference
      shades to reproduce the shade tabs. Disks were fabricated from the prescriptions,
      polished to 1.0 mm thickness, then placed over a zirconia core plate and measured
      with the spectrophotometer. The color differences (DeltaE*) between the shade
      tabs and the corresponding ceramic disks were calculated. Statistical analysis
      was performed with the 1-sample t test. RESULTS: The DeltaE* values between
      computer color matching specimens and the target shade tabs varied from 0.5 to
      1.9, with an average DeltaE* of 1.3, which was significantly less than the
      clinically detectable DeltaE* threshold of 1.6 (P<.001). CONCLUSIONS: The
      computer color matching system with the established 21 new shades is accurate and
      effective for reproducing tooth shades.

PMID- 24286639
TI  - Accurate transfer of soft tissue morphology with interim prosthesis to definitive
      cast.
AB  - With conventional fixed dental prostheses, the interim restoration is a valuable
      diagnostic tool in the evaluation of esthetics and function. To achieve
      predictable definitive esthetic results, information about the subgingival and
      the supragingival contour of a properly designed restoration should be
      communicated to the dental laboratory technician. The technique described enables
      the accurate transfer of the soft tissue morphology developed with an interim
      prosthesis to the definitive cast. This modified definitive cast allows the
      dental laboratory technician to fabricate a restoration with an emergence profile
      identical to that of the interim prosthesis. 

PMID- 24286640
TI  - Is there a link between tinnitus and temporomandibular disorders?
AB  - STATEMENT OF PROBLEM: The frequent concurrence of tinnitus and temporomandibular
      joint and masticatory muscle disorders (TMD) has led to the assumption that a
      possible relationship exists between these 2 conditions. PURPOSE: The present
      prospective clinical study was conducted to assess the possible association
      between tinnitus and TMD and to investigate the effect of stomatognathic therapy
      on tinnitus distress. MATERIAL AND METHODS: The prevalence of TMD and tinnitus
      was investigated in a consecutive series of 951 patients at the Department of
      Prosthetic Dentistry at the University Medical Center Regensburg, Germany.
      Patients with TMD and simultaneous tinnitus were included in the prospective
      clinical trial (n=25). Baseline examination comprised a detailed functional
      analysis, diagnosis of temporomandibular joint and masticatory muscle disorder,
      and a tinnitus questionnaire. All the participants received individual dental
      functional therapy (oral splints, physiotherapy). The effects of functional
      therapy on TMD and tinnitus symptoms were examined 3 to 5 months after the
      initiation of dental functional therapy. Means (standard deviations) were
      calculated, and 1-way ANOVA was used to investigate statistical differences
      (alpha=.05). The differences of the 2 binary outcomes were compared with the
      Pearson chi(2) test, and the relative risk was calculated. RESULTS: Prevalence of
      tinnitus was found to be 8 times higher in participants with TMD (30 of 82
      [36.6%]) than in participants without TMD (38 of 869 [4.4%]). All the
      participants with unilateral TMD and unilateral tinnitus showed these conditions
      on the same side. Stomatognathic therapy improved tinnitus symptoms in 11 of 25
      participants (44%). CONCLUSIONS: The results of this study and the prospective
      clinical trial showed a significant correlation between tinnitus and TMD. The
      observed treatment outcome suggests that dental functional therapy may have a
      positive effect on TMD-related tinnitus.

PMID- 24286641
TI  - An alternative impression technique for complete dentures.
AB  - This article describes a technique for creating adequate space for an even
      thickness of polyvinyl siloxane (PVS) impression material at the periphery during
      complete denture impression making. A PVS border molding material is injected
      around the borders of a custom tray, a 17-MUm-thick stretch wrap film is folded
      into 4 layers, and a tray-shaped piece slightly larger than the size of the
      custom tray is placed on the tray covering the borders. After the border molding
      procedure is completed, the film is removed and the definitive impression
      completed with a medium-viscosity PVS impression material. 

PMID- 24286642
TI  - microRNAs in breast cancer development and treatment.
AB  - microRNAs (herein after miRNAs) represent a recently uncovered class of small and
      endogenous non-coding RNAs. miRNAs play a well conserved and crucial role in
      normal biological processes, such as cell differentiation, proliferation and
      apoptosis through a complicated gene regulation networking. The recent rise of
      interest in miRNAs in cancer research is ascribed to the breakthrough of their
      role in many pathological processes, including malignant transformation. miRNAs
      signatures have been clearly defined for certain types of cancer, with
      correlation to tumor aggressiveness, therapy response and patient outcome.
      Furthermore, the use of miRNAs as therapeutic targets for cancer is currently
      under investigation. The aim of this review is to focus on the role of miRNAs in
      breast cancer development and to summarize the evidence for their potential
      diagnostic and therapeutic applications in clinical practice. 

PMID- 24286643
TI  - Evidence-based prosthodontics: fundamental considerations, limitations, and
      guidelines.
AB  - Evidence-based dentistry is rapidly emerging to become an integral part of
      patient care, dental education, and research. Prosthodontics is a unique dental
      specialty that encompasses art, philosophy, and science and includes reversible
      and irreversible treatments. It not only affords good applicability of many
      principles of evidence-based dentistry but also poses numerous limitations. This
      article describes the epidemiologic background, fundamental considerations,
      scrutiny of levels of evidence, limitations, guidelines, and future perspectives
      of evidence-based prosthodontics. Understanding these principles can aid
      clinicians in appropriate appraisal of the prosthodontics literature and use the
      best available evidence for making confident clinical decisions and optimizing
      patient care. 

PMID- 24286644
TI  - Occlusal stability.
AB  - Occlusion is the foundation for clinical success in fixed, removable, and implant
      prosthodontic treatment. Understanding those principles is critical when
      restoring a patient's occlusion. Many philosophies, devices, and theories of
      occlusion have evolved based on anecdotal clinical observations and applied
      geometric perceptions. The literature has reported these classic and contemporary
      occlusal concepts. As evidence-based dentistry emerged, it championed scrutiny of
      previously held beliefs, resulting in the abandonment of many pragmatic, yet
      beneficial occlusal procedures. The impetus toward scientific discovery, whereby
      factual information might be universally applied in dental education and clinical
      practice, has renewed interest in occlusal studies. 

PMID- 24286645
TI  - Gingival displacement for impression making in fixed prosthodontics: contemporary
      principles, materials, and techniques.
AB  - The clinical success and longevity of indirect restorations depend on the careful
      and accurate completion of several procedures. One of the challenging procedures
      is management of the gingival tissues and gingival esthetics. The goal for
      management of gingival tissues and gingival esthetics is to maintain the normal
      appearance of healthy gingival. Achieving this goal requires optimal health
      before treatment and minimal trauma during treatment. The best way of optimizing
      health and minimizing trauma is to avoid contacting the gingiva with restorative
      materials. 

PMID- 24286646
TI  - Removable partial dentures: clinical concepts.
AB  - This article provides a review of the traditional clinical concepts for the
      design and fabrication of removable partial dentures (RPDs). Although classic
      theories and rules for RPD designs have been presented and should be followed,
      excellent clinical care for partially edentulous patients may also be achieved
      with computer-aided design/computer-aided manufacturing technology and unique
      blended designs. These nontraditional RPD designs and fabrication methods provide
      for improved fit, function, and esthetics by using computer-aided design
      software, composite resin for contours and morphology of abutment teeth, metal
      support structures for long edentulous spans and collapsed occlusal vertical
      dimensions, and flexible, nylon thermoplastic material for metal-supported clasp
      assemblies. 

PMID- 24286647
TI  - Alternatives to traditional complete dentures.
AB  - Specific alternatives to traditional complete denture therapy have been
      controversial because of the uncertainties surrounding effectiveness of
      retention. This article addresses the importance of retention, border molding,
      diagnosis, and treatment planning, and the meticulous attention to detail
      required throughout the treatment course of these alternative modalities.
      Indications, advantages, and limitations are also presented. Although these
      alternatives are not routinely used in making complete dentures, they have been
      successfully used for the treatment of the edentulous patient. Alternatives serve
      as valuable prosthodontic treatment options that greatly enhance denture
      aesthetics, and should be considered for edentulous patients. 

PMID- 24286648
TI  - Geriatric prosthodontic care.
AB  - The geriatric population (age 65 and older) is the fastest growing segment
      nationally and globally. The large population will continue to increase because
      of baby boomers that have recently turned 65 years old. Within this cohort, there
      is much diversity in health, socioeconomic levels, education, and health beliefs.
      There is a decline in edentulism yet still there are oral health conditions that
      persist with age, such as caries, tooth loss, and increased needs for
      prosthodontic dental treatment. Several factors should be taken into account in
      geriatric prosthodontic care, including quality of life and psychosocial needs.

PMID- 24286649
TI  - Latest biomaterials and technology in dentistry.
AB  - Navigation technology is applied successfully in oral and maxillofacial surgery.
      Laser beams are used for caries removal. With nanodentistry, it is possible to
      maintain comprehensive oral health care. Nanorobots induce oral analgesia,
      desensitize teeth, and manipulate the tissue. They can also be used for
      preventive, restorative, and curative procedures. Strategies to engineer tissue
      can be categorized into 3 major classes: conductive, inductive, and cell
      transplantation approaches. Several populations of cells with stem cell
      properties have been isolated from different parts of the tooth. 

PMID- 24286651
TI  - Management of snoring and obstructive sleep apnea with mandibular repositioning
      appliances: a prosthodontic approach.
AB  - Dentists are becoming increasingly aware of the importance of the detection and
      management of obstructive sleep apnea. The anatomic and neuromuscular risk
      factors in the pathogenesis of obstructive sleep apnea are reviewed with
      particular emphasis on oral findings. Mandibular repositioning appliances hold an
      important role in the treatment of this condition; however, knowledge of
      indications and contraindications for treatment, potential areas of oropharyngeal
      obstruction, appliance design, and treatment steps are vital to ensure maximum
      treatment success. A review of the steps involved in treatment and management
      with particular emphasis on collaborative care with physicians is presented. 

PMID- 24286650
TI  - Digital imaging and fabrication.
AB  - Bioceramics have been adopted in dental restorations for implants, bridges,
      inlays, onlays, and all-ceramic crowns. Dental bioceramics include glass
      ceramics, reinforced porcelains, zirconias, aluminas, fiber-reinforced ceramic
      composites, and multilayered ceramic structures. The process of additive
      manufacturing is ideally suited to dentistry. Models are designed using data from
      a computed tomography scan or magnetic resonance imaging. Since its development
      in 2001, direct ceramic machining of presintered yttria tetragonal zirconia
      polycrystal has become increasingly popular in dentistry. There are wide variety
      commercially available cements for luting all-ceramic restorations. However,
      resin cements have lower solubility and better aesthetic characteristics. 

PMID- 24286652
TI  - Radiographic stents: integrating treatment planning and implant placement.
AB  - The pivotal point in treatment planning for dental implants occurs when the
      location of bone is viewed radiographically in the context of the planned
      prosthesis. Radiographic planning for dental implant therapy should be used only
      after a review of the patient's systemic health, imaging history, oral health,
      and local oral conditions. The radiological diagnostic and planning procedure for
      dental implants can only be fully achieved with the use of a well-designed and 
      constructed radiographic guide. This article reviews several methods for
      construction of radiographic guides and how they may be utilized for improving
      implant surgery planning and performance. 

PMID- 24286653
TI  - Patient selection and treatment planning for implant restorations.
AB  - Dental implants are an indispensible tool for the restoration of missing teeth.
      Their use has elevated the practice of dentistry by improving both our technical
      ability to rehabilitate patients and general quality of life. To routinely
      achieve the associated high expectations, diligent attention to details must be
      observed and addressed from the outset. Of central concern is the attainment of
      osseointegration and the location of implants to ideally support the intended
      restoration. The pivotal point in treatment planning for dental implants occurs
      when the location of bone is viewed radiographically in the context of the
      planned prosthesis. This most often requires diagnostic waxing or tooth
      arrangement using mounted diagnostic casts. 

PMID- 24286654
TI  - Prosthodontic management of implant therapy.
AB  - Implant-supported dental restorations can be screw-retained, cement-retained, or
      a combination of both, whereby a metal superstructure is screwed to the implants
      and crowns are individually cemented to the metal frame. Each treatment modality
      has advantages and disadvantages. The use of computer-aided design/computer
      assisted manufacture technologies for the manufacture of implant superstructures
      has proved to be advantageous in the quality of materials, precision of the
      milled superstructures, and passive fit. Maintenance and recall evaluations are
      an essential component of implant therapy. The longevity of implant restorations
      is limited by their biological and prosthetic maintenance requirements. 

PMID- 24286655
TI  - Caries management by risk assessment care paths for prosthodontic patients: oral
      microbial control and management.
AB  - The development of an oral care path focuses on the identification of the early
      indicators of disease. Once the risks have been identified and diagnosed, the
      proper therapies can be selected and prescribed. The experienced practitioner
      must meld clinical experience and observation with evidence-based scientific
      dentistry and information on the treatment and prevention of continued disease
      for the prosthodontic patient after restorations have been completed. The
      incorporation of dental implants has not allowed for complications of caries and
      periodontal disease on teeth and implants. Osseoseparation is necessary for
      justification of continued maintenance. 

PMID- 24286656
TI  - A critically appraised topic review of computer-aided design/computer-aided
      machining of removable partial denture frameworks.
AB  - A critically appraised topic (CAT) review is presented about the use of computer
      aided design (CAD)/computer-aided machining (CAM) removable partial denture (RPD)
      frameworks. A systematic search of the literature supporting CAD/CAM RPD systems
      revealed no randomized clinical trials, hence the CAT review was performed. A
      PubMed search yielded 9 articles meeting the inclusion criteria. Each article was
      characterized by study design and level of evidence. No clinical outcomes
      research has been published on the use of CAD/CAM RPDs. Low levels of evidence
      were found in the available literature. Clinical research studies are needed to
      determine the efficacy of this treatment modality. 

PMID- 24286657
TI  - Dental Clinics of North America. Prosthodontics. Preface.

PMID- 24286658
TI  - Shear-induced hydrodynamic cavitation as a tool for pharmaceutical
      micropollutants removal from urban wastewater.
AB  - In this study, the removal of clofibric acid, ibuprofen, naproxen, ketoprofen,
      carbamazepine and diclofenac residues from wastewater, using a novel shear
      induced cavitation generator has been systematically studied. The effects of
      temperature, cavitation time and H2O2 dose on removal efficiency were
      investigated. Optimisation (50 degrees C; 15 min; 340 mg L(-1) of added H2O2)
      resulted in removal efficiencies of 47-86% in spiked deionised water samples.
      Treatment of actual wastewater effluents revealed that although matrix
      composition reduces removal efficiency, this effect can be compensated for by
      increasing H2O2 dose (3.4 g L(-1)) and prolonging cavitation time (30 min).
      Hydrodynamic cavitation has also been investigated as either a pre- or a post
      treatment step to biological treatment. The results revealed a higher overall
      removal efficiency of recalcitrant diclofenac and carbamazepine, when
      hydrodynamic cavitation was used prior to as compared to post biological
      treatment i.e., 54% and 67% as compared to 39% and 56%, respectively. This is an
      important finding since diclofenac is considered as a priority substance to be
      included in the EU Water Framework Directive.

PMID- 24286659
TI  - Ultrasound assisted reduction of graphene oxide to graphene in L-ascorbic acid
      aqueous solutions: kinetics and effects of various factors on the rate of
      graphene formation.
AB  - The reduction of graphene oxide (GO) to graphene (rGO) was achieved by using 20
      kHz ultrasound in L-ascorbic acid (L-AA, reducing agent) aqueous solutions under
      various experimental conditions. The effects of ultrasound power, ultrasound
      pulse mode, reaction temperature, pH value and L-AA amount on the rates of rGO
      formation from GO reduction were investigated. The rates of rGO formation were
      found to be enhanced under the following conditions: high ultrasound power, long
      pulse mode, high temperature, high pH value and large amount of L-AA. It was also
      found that the rGO formation under ultrasound treatment was accelerated in
      comparison with a conventional mechanical mixing treatment. The pseudo rate and
      pseudo activation energy (Ea) of rGO formation were determined to discuss the
      reaction kinetics under both treatment. The Ea value of rGO formation under
      ultrasound treatment was clearly lower than that obtained under mechanical mixing
      treatment at the same condition. We proposed that physical effects such as shear
      forces, microjets and shock waves during acoustic cavitation enhanced the mass
      transfer and reaction of L-AA with GO to form rGO as well as the change in the
      surface morphology of GO. In addition, the rates of rGO formation were suggested
      to be affected by local high temperatures of cavitation bubbles.

PMID- 24286660
TI  - A novel Cry9Aa with increased toxicity for Spodoptera exigua (Hubner).
AB  - Cry9Aa, produced by Bacillus thuringiensis is reported to be not active against
      Spodoptera exigua (beet armyworm). In this study we have cloned a new cry9Aa5
      gene encoding a protoxin with increased activity against S. exigua as compared to
      Cry9Aa1. When aligned to Cry9Aa1, four amino acid substitutions in domain I and
      one substitution in the C-terminal protein extension of Cry9Aa5 were identified.
      Toxicity of Cry9Aa5, produced in recombinant Escherichia coli was assessed and
      compared to the activity of Cry9Aa1, produced under the same conditions. 

PMID- 24286661
TI  - PVC bacteria: variation of, but not exception to, the Gram-negative cell plan.
AB  - Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacteria have features that
      differentiate them from classical Gram-negative (G-) bacteria. One such feature
      is their complex endomembrane system. Based on the difference of membrane
      organization and compartment identity, PVC bacteria were proposed to form an
      exception to the bacterial G- cell plan. Here I argue that all PVC membranes are
      derived from G- membranes, and that their organization and the compartments they
      form are similar to those of G- bacteria. I suggest that PVC membrane
      organization should be evaluated within a G- framework and as a variation of it. 

PMID- 24286662
TI  - Peripheral CD24hi CD27+ CD19+ B cells subset as a potential biomarker in naive
      systemic lupus erythematosus.
AB  - AIM: B cells are likely to play critical roles in the pathogenesis of systemic
      lupus erythematosus (SLE). Our aim was to investigate the role of peripheral
      CD24(hi) CD27(+) CD19(+) B cells in Chinese patients with new-onset SLE. METHOD:
      Peripheral CD24(hi) CD27(+) CD19(+) B cells were analyzed in 55 new-onset lupus
      and 36 healthy controls by flow cytometry. All SLE cases were treated with
      prednisolone and hydroxychloroquine during a 1-year follow-up. Thirteen cases
      were added with cyclophosphamide or mycophenolate mofetil. The CD24(hi) CD27(+)
      CD19(+) B cells were analyzed at days 0, 7, 14 and months 1, 3, 6, 9 and 12.
      Interleukin-10 (IL-10)-producing B cell was detected in eight naive lupus and 10
      healthy controls. RESULTS: Compared to healthy controls, the frequency and number
      of primary circulating CD24(hi) CD27(+) CD19(+) B cells was significantly reduced
      in SLE cases (8.22 +/- 3.48% vs. 31.67 +/- 5.53%, P < 0.0001; 4.04 +/- 2.85 vs.
      38.66 +/- 10.22 10(3) cells/mL, P = 0.0001) before treatment; IL-10(+) CD19(+) B
      cells and IL-10(+) CD24(hi) CD27(+) CD19(+) B cells also decreased in SLE.
      Interestingly, primary CD24(hi) CD27(+) CD19(+) B cells inversely correlated with
      SLE disease activity index (SLEDAI) score. Patients with arthritis and
      hematologic disorders had a lower primary CD24(hi) CD27(+) CD19(+) B cells. In 48
      SLE cases who finished the 1-year follow-up, the frequency and number of CD24(hi)
      CD27(+) CD19(+) B cells increased from 8.26 +/- 3.61% to 25.51 +/- 4.56%; 3.99 +/
      2.86 to 28.64 +/- 11.81 10(3) cells/mm(3) (P < 0.0001), accompanied by a
      significantly decreased SLEDAI score. Of note, CD24(hi) CD27(+) CD19(+) B cells
      decreased in some flare cases with an elevated SLEDAI score. CONCLUSION: These
      results demonstrate that a lower primary CD24(hi) CD27(+) CD19(+) B cells may be
      an immunologic aspect of new-onset SLE. CD24(hi) CD27(+) CD19(+) B cells may be a
      useful tool to evaluate lupus activity and monitor the response to therapy.

PMID- 24286663
TI  - Efficacy of argon plasma coagulation in the treatment of radiation-induced
      hemorrhagic gastroduodenal vascular ectasia.
AB  - OBJECTIVE: Radiation-induced hemorrhagic gastroduodenal vascular ectasia (GDVE)
      is rare but difficult to manage. Argon plasma coagulation (APC) has not yet been
      evaluated in the treatment of radiation-induced hemorrhagic GDVE. The efficacy of
      APC in patients with radiation-induced hemorrhagic GDVE has been investigated in
      this article. MATERIAL AND METHODS: Eighteen patients with upper gastrointestinal
      (GI) bleeding caused by radiation-induced GDVE, including 13 with hepatocellular
      carcinoma, 3 with pancreatic cancer, and 2 with cholangiocarcinoma, were treated
      with APC. The efficacy of APC was retrospectively evaluated, based on cessation
      of macroscopic GI bleeding, resolution or stabilization of anemia and transfusion
      dependence, endoscopic ablation of almost all vascular lesions, complications,
      and recurrence. RESULTS: Mean patient age was 59 years (range 42-80 years). The
      median time from radiation to GDVE diagnosis was 4.6 months (range 3.3-21.5
      months). The median number of APC sessions per patient was 2.4 (range 1-4). All
      18 patients showed an endoscopic response to APC treatment, with sustained
      increases in mean hemoglobin level, from 6.6 g/dL (range 2.9-9.5 g/dL) to 9.7
      g/dL (range 7.1-12.7 g/dL) (p < 0.001), and decreased dependence on transfusion,
      from 9.1 (range 0-30) to 4.1 (range 0-15) units of packed red blood cells per
      patient (p = 0.038) after last endoscopic eradication by APC treatment. There
      were no major procedure-related adverse events or deaths. At a median follow up
      of 4.7 months (range 0.6-24.5 months), none of the patients experienced
      recurrence of GDVE. CONCLUSIONS: APC showed short-term effectiveness and safety
      in the treatment of radiation-induced hemorrhagic GDVE.

PMID- 24286664
TI  - Communication with patients with trauma who were in spinal immobilization.

PMID- 24286665
TI  - Headache: a rare manifestation of Debakey type I aortic dissection.
AB  - The most common manifestations of aortic dissection (AD) are severe chest pain
      and back pain. However, we experienced a rare case of type I aortic dissection
      with bilateral common carotid artery involvement, which presented with only a
      sudden thunderclap bifrontal headache.

PMID- 24286666
TI  - Rotational thromboelastometry along with thromboelastography plays a critical
      role in the management of traumatic bleeding.
AB  - Massive posttraumatic bleeding is the leading cause of potentially preventable
      death among patients with severe trauma. Immediate diagnosis and treatment of
      traumatic coagulopathy and its differentiation from surgical bleeding after major
      trauma are critical in the management of such patients. In this case report, we
      present a 33-year-old woman who had multiple injuries to the head and trunk in
      motor vehicle collision, resulting in severe bleeding and necessitating emergency
      surgery. We demonstrate how repeated rotational thromboelastometry and
      thromboelastography analyses were used to direct the choice of therapy to
      stabilize her circulatory system for surgery and to differentiate surgical bleed
      from coagulopathy. Therapy based on massive transfusion protocol and on
      laboratory coagulation tests would be insufficient to stop bleeding. We conclude
      that rotational thromboelastometry/thromboelastography analysis plays a critical
      role in the management of traumatic bleeding and helps us provide more aggressive
      and targeted therapy for coagulopathy both in the acute and later phases of
      treatment of severe bleeding.

PMID- 24286667
TI  - Isolated splenic peliosis with spontaneous rupture after a viperine bite.
AB  - Isolated splenic peliosis is an extremely uncommon condition that can present
      with atraumatic rupture and potential fatal outcome. We here report 1 such case
      that developed after a viperine bite in a 21-year-old woman. The case highlights
      the diagnostic findings on computed tomographic (CT) scan and its potential
      complications.

PMID- 24286668
TI  - Massive cerebrovascular air embolism during posttraumatic cardiopulmonary
      resuscitation.
AB  - Air embolism is known to be a complicating factor in several clinical settings,
      including thoracic, cardiovascular, and neurosurgical operations; central line
      placement; and penetrating thoracic and cranial trauma. There are, however, only
      few case descriptions for cardiopulmonary resuscitation massive cerebral air
      embolism, and the frequency of this supposedly rare complication is unknown.
      Computed tomography is useful for showing cerebral air embolism. In this report,
      we present a 16-year-old adolescent girl with cerebrovascular air embolism on
      computed tomographic examination after a posttraumatic cardiopulmonary
      resuscitation and discuss the reasonable mechanisms of cerebrovascular air
      embolism.

PMID- 24286670
TI  - Clinical commentary in response to: mechanosensitivity in the upper extremity
      following breast cancer treatment.

PMID- 24286669
TI  - The substrate binding interface of alkylpurine DNA glycosylase AlkD.
AB  - Tandem helical repeats have emerged as an important DNA binding architecture. DNA
      glycosylase AlkD, which excises N3- and N7-alkylated nucleobases, uses repeating
      helical motifs to bind duplex DNA and to selectively pause at non-Watson-Crick
      base pairs. Remodeling of the DNA backbone promotes nucleotide flipping of the
      lesion and the complementary base into the solvent and toward the protein
      surface, respectively. The important features of this new DNA binding
      architecture that allow AlkD to distinguish between damaged and normal DNA
      without contacting the lesion are poorly understood. Here, we show through
      extensive mutational analysis that DNA binding and N3-methyladenine (3mA) and N7
      methylguanine (7mG) excision are dependent upon each residue lining the DNA
      binding interface. Disrupting electrostatic or hydrophobic interactions with the
      DNA backbone substantially reduced binding affinity and catalytic activity. These
      results demonstrate that residues seemingly only involved in general DNA binding
      are important for catalytic activity and imply that base excision is driven by
      binding energy provided by the entire substrate interface of this novel DNA
      binding architecture. 

PMID- 24286671
TI  - L-3-n-Butylphthalide protects rats' cardiomyocytes from ischaemia/reperfusion
      induced apoptosis by affecting the mitochondrial apoptosis pathway.
AB  - AIMS: This study investigated the role of L-3-n-Butylphthalide (NBP) in cardiac
      protection. METHODS: The left anterior descending coronary arteries (LAD) of the
      rats were occluded for 30 min following by 2-h reperfusion to make the
      ischaemia/reperfusion models. Neonatal cardiomyocytes were cultured and subjected
      to hypoxia. L-3-n-Butylphthalide was administered intraperitoneally 2 h before
      the surgery and right after the reperfusion in the in vivo experiments or added
      to the culture medium in vitro. Haemodynamic parameters were recorded to evaluate
      the cardiac functions, triphenyltetrazolium chloride (TTC) and Evens blue
      staining were used to determine the area of risk and infarct area, apoptotic cell
      numbers were counted with terminal deoxynucleotidyl transferase dUTP nick end
      labelling (TUNEL) staining. Western blotting was used to determine the apoptotic
      protein levels and immune staining to determine the translocation of
      Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein. RESULTS: Our research
      showed for the first time that L-3-n-Butylphthalide had great effects in
      improving cardiac hemodynamic function and decreasing cardiac infarct areas and
      apoptotic cell numbers in the peri-infarct areas. The apoptotic signals
      investigation showed that L-3-n-Butylphthalide affected the mitochondrial pathway
      including Bcl-2 protein expression, inhibition of caspase 3 activation and
      cytochrome C releasing. Besides, Glyceraldehyde-3-phosphate dehydrogenase protein
      translocation was inhibited by L-3-n-Butylphthalide treatment, and this effect
      was mediated by endogenous reactive oxygen species (ROS). CONCLUSION: L-3-n
      Butylphthalide protects cardiomyocytes from ischaemia/reperfusion-induced
      apoptosis by antioxidant effect and affecting mitochondrial apoptotic pathway.

PMID- 24286673
TI  - Outcomes of infrapopliteal endoluminal intervention for transatlantic
      intersociety consensus C and D lesions in patients with critical limb ischaemia.
AB  - BACKGROUND: Recent data suggest that infrapopliteal percutaneous transluminal
      angioplasty (PTA) is a reasonable primary therapy for critical limb ischaemia
      (CLI). Based on the transatlantic intersociety consensus (TASC) classification,
      this has been found to be true for lesions classified as A, B or C. We report our
      experience with infrapopliteal PTA stratified by TASC classification. METHODS: A
      retrospective study of patients who underwent infrapopliteal PTA with or without
      stenting from October 2007 to July 2011 was conducted, revealing 83 limbs. The
      primary outcome variables were freedom from reintervention and freedom from index
      limb amputation. Secondary outcomes were technical success, post-operative
      complications and survival. TASC classification was assessed for the individual
      vessel(s) chosen for intervention. RESULTS: Median age was 76 years and
      radiological success was 86.75%. Average follow-up was 15 months. At 1 and 2
      years, freedom from re-intervention, or amputation was 65.1% and 55.6%. Limb
      salvage was 77.7%. Within 2 years, 2% underwent bypass and 18% repeat
      infrapopliteal PTA. The 30-day mortality was 5%. Overall survival was 84.5%,
      71.8% and 61.6% at 1, 2 and 3 years. Eighty-two per cent were classified as TASC
      D lesions. Radiological success was achieved in 100% of TASC C lesions in
      contrast to 86.7% of TASC D lesions. There was not a statistically significant
      relationship between primary outcomes and TASC D classification. DISCUSSION:
      Given the encouragingly high rates of radiological success and limb salvage, an
      attempt at PTA is indicated as an alternative to primary amputation even in
      patients with radiologically demonstrated severe disease.

PMID- 24286672
TI  - Genetically encoded fluorescent indicator for imaging NAD(+)/NADH ratio changes
      in different cellular compartments.
AB  - BACKGROUND: The ratio of NAD(+)/NADH is a key indicator that reflects the overall
      redox state of the cells. Until recently, there were no methods for real time
      NAD(+)/NADH monitoring in living cells. Genetically encoded fluorescent probes
      for NAD(+)/NADH are fundamentally new approach for studying the NAD(+)/NADH
      dynamics. METHODS: We developed a genetically encoded probe for the nicotinamide
      adenine dinucleotide, NAD(H), redox state changes by inserting circularly
      permuted YFP into redox sensor T-REX from Thermus aquaticus. We characterized the
      sensor in vitro using spectrofluorometry and in cultured mammalian cells using
      confocal fluorescent microscopy. RESULTS: The sensor, named RexYFP, reports
      changes in the NAD(+)/NADH ratio in different compartments of living cells. Using
      RexYFP, we were able to track changes in NAD(+)/NADH in cytoplasm and
      mitochondrial matrix of cells under a variety of conditions. The affinity of the
      probe enables comparison of NAD(+)/NADH in compartments with low (cytoplasm) and
      high (mitochondria) NADH concentration. We developed a method of eliminating pH
      driven artifacts by normalizing the signal to the signal of the pH sensor with
      the same chromophore. CONCLUSION: RexYFP is suitable for detecting the NAD(H)
      redox state in different cellular compartments. GENERAL SIGNIFICANCE: RexYFP has
      several advantages over existing NAD(+)/NADH sensors such as smallest size and
      optimal affinity for different compartments. Our results show that normalizing
      the signal of the sensor to the pH changes is a good strategy for overcoming pH
      induced artifacts in imaging.

PMID- 24286674
TI  - Why otolaryngologists and asthma are a good match: the allergic rhinitis-asthma
      connection.
AB  - Consideration of the unified airway model when managing patients with rhinitis
      and or asthma allows a more comprehensive care plan and therefore improved
      patient outcomes. Asthma is linked to rhinitis both epidemiologically and
      biologically, and this association is even stronger in individuals with atopy.
      Rhinitis is not only associated with but is a risk factor for the development of
      asthma. Management of rhinitis improves asthma control. Early and aggressive
      treatment of allergic rhinitis may prevent the development of asthma. In patients
      with allergic rhinitis that is not sufficiently controlled by allergy medication,
      allergen-directed immunotherapy should be considered. 

PMID- 24286675
TI  - What is asthma? Pathophysiology, demographics, and health care costs.
AB  - Asthma is an obstructive pulmonary disorder with exacerbations characterized by
      symptoms of shortness of breath, cough, chest tightness, and/or wheezing.
      Symptoms are caused by chronic airway inflammation. There are multiple cell types
      and inflammatory mediators involved in its pathophysiology. The airway
      inflammation is frequently mediated by Th2 lymphocytes, whose cytokine secretion
      leads to mast cell stimulation, eosinophilia, leukocytosis, and enhanced B-cell
      IgE production. Although various genes have been identified as likely
      contributors to asthma development, asthma is largely environmentally triggered
      and has a multifactorial cause. Asthma is extremely common, especially in poor,
      urban environments. Asthma is the third most common reason for pediatric
      hospitalizations. 

PMID- 24286676
TI  - Asthma: symptoms and presentation.
AB  - The goal of this article is to inform readers of the common and uncommon signs
      and symptoms of asthma. After completion of this article, readers should have a
      firm understanding of the symptoms and presentation leading to a diagnosis of
      asthma. 

PMID- 24286677
TI  - Asthma diagnosis in otolaryngology practice: pulmonary function testing.
AB  - Pulmonary function testing is an important diagnostic modality in the workup of
      patients suspected of having asthma. It is also valuable for monitoring response
      to treatment in patients initiated and sustained on asthma therapy, and for
      assessing patients with symptoms suggestive of an asthma exacerbation. Spirometry
      is the most useful test in patients suspected of having asthma, and can easily be
      performed and interpreted in the otolaryngology office with readily available,
      inexpensive equipment. Pulmonary function testing should be considered for use in
      all otolaryngology patients with significant rhinitis and in those suspected of
      having lower respiratory disease. 

PMID- 24286678
TI  - Interpreting spirometry: the basics.
AB  - The ability to accurately obtain and interpret spirometry is essential for
      physicians caring for patients with asthma and inflammatory disease of the
      airway. This article reviews the basic equipment, setting, and personnel needed
      to obtain quality spirometric data. The fundamental measurements obtained in
      routine office spirometry and recommendations that are critical to obtaining high
      quality reproducible test results are reviewed. The evaluation of flow-volume
      loops and normative data is discusses as well as criteria that define a quality
      measurement. Examples of normal spirometric data as well as data from different
      disease states are reviewed. 

PMID- 24286679
TI  - Asthma pharmacotherapy.
AB  - Asthma is a chronic inflammatory disease of the airway that leads to airway
      obstruction via bronchoconstriction, edema, and mucus hypersecretion. The
      National Asthma Education and Prevention Program has outlined evidence-based
      guidelines to standardize asthma therapy and improve outcomes. The initial
      recommendation of choice for persistent asthmatic patients is an inhaled
      corticosteroid (ICS). Long-acting beta-2 agonists in combination with ICS, oral
      corticosteroids, leukotriene modifiers, and anti-IgE therapeutic options can be
      considered for patients with persistent or worsening symptoms. Many novel
      therapies are being developed, with an emphasis on anti-inflammatory mechanisms,
      gene expression, and cytokine modification. 

PMID- 24286680
TI  - Stepwise treatment of asthma.
AB  - Therapy for asthma has undergone substantial changes in the past three decades,
      prompted by a better understanding of the role of inflammation in reversible
      airway disease. Improved therapies and a workable algorithm of therapy guidelines
      have provided an improved quality of life for the patient with asthma. This
      article outlines the most recent revisions of the stepwise guidelines provided by
      the National Heart, Lung, and Blood Institute. 

PMID- 24286681
TI  - Bronchial thermoplasty.
AB  - Bronchial thermoplasty is a relatively new therapy for the management of severe
      asthma. It involves the direct bronchoscopic application of thermal energy to
      airways by a catheter-directed expandable basket. The airways of the lower and
      upper lobes are treated in 3 separate sessions spaced 3 weeks apart. The therapy
      targets airway smooth muscle, with studies showing a decrease in airway smooth
      muscle after bronchial thermoplasty therapy. After therapy, an improvement in
      quality of life and decrease in asthma exacerbations can be expected. Adverse
      events can occur with bronchial thermoplasty and careful patient selection is
      critical to ensure benefits outweigh the potential risks.

PMID- 24286682
TI  - The role of fractional exhaled nitric oxide in asthma management.
AB  - Measuring fractional exhaled nitric oxide (FeNO) is a relatively new option for
      assessing allergic inflammation in the lungs. Clinical management of asthma is
      challenging, and measuring exhaled nitric oxide can provide another type of data
      to assist in meeting this challenge. FeNO is easy to perform, and the equipment
      is not forbiddingly expensive. FeNO provides a complement to traditional measures
      of asthma control and can help guide diagnostic and treatment choices. This
      article explains what it is, how the measurements are performed, what the norms
      are, and its use and limitations in the management of asthma. 

PMID- 24286683
TI  - Should vitamin D supplementation be a regular part of asthma care?
AB  - Vitamin D (vitD3) deficiency occurs frequently and has profound effects on
      health, especially asthma. This article examines how current knowledge of vitD3
      actions and the worldwide distribution of vitD3 deficiency influences everyday
      clinical allergy practice. Within the limits of current knowledge, the article
      concisely explains the molecular nature of vitD3 actions, reviews key vitD3
      research as it applies to clinical care, answers questions about the potential
      clinical impact of low vitD3 levels, and discusses use and safety of vitD3
      supplements. 

PMID- 24286684
TI  - Identifying asthma triggers.
AB  - Asthma has many triggers including rhinosinusitis; allergy; irritants;
      medications (aspirin in aspirin-exacerbated respiratory disease); and obesity.
      Paradoxic vocal fold dysfunction mimics asthma and may be present along with
      asthma. This article reviews each of these triggers, outlining methods of
      recognizing the trigger and then its management. In many patients more than one
      trigger may be present. Full appreciation of the complexity of these
      relationships and targeted therapy to the trigger is needed to best care for the
      patient with asthma. 

PMID- 24286685
TI  - Exercise-induced bronchoconstriction.
AB  - Exercise-induced bronchoconstriction (EIB) occurs commonly in patients with
      asthma but also can affect individuals without asthma. EIB is particularly common
      in populations of athletes. Common symptoms include cough, dyspnea, chest
      tightness, and wheezing; however, there can be a variety of more subtle symptoms.
      In this article, the clinical presentation of EIB as well as the diagnosis and
      treatment of EIB are outlined. 

PMID- 24286686
TI  - Patient education and designing an asthma action plan.
AB  - In this article asthma assessment and patient education protocol for the Oto
      Allergy Clinic at Wexner Medical Center at The Ohio State University Department
      of Otolaryngology, Division of Sinus and Allergy, are shared. 

PMID- 24286687
TI  - Paradoxic vocal fold movement disorder.
AB  - Paradoxical Vocal Fold Movement Disorder (PVFMD) is a cause of dyspnea that can
      mimic or occur alongside asthma or other pulmonary disease. Treatment with
      Laryngeal Control Therapy is very effective once the entity is properly diagnosed
      and contributing comorbidities are managed appropriately. In understanding the
      etiology of PVFMD, focus has broadened beyond psychiatric factors alone to
      include the spectrum of laryngeal irritants (laryngopharyngeal reflux, allergic
      and sinus disease, sicca, and possibly obstructive sleep apnea). The following is
      a discussion of the history, terminology, epidemiology, diagnosis, comorbid
      conditions, and treatment of this entity. 

PMID- 24286688
TI  - Other asthma considerations.
AB  - Asthma is a heterogeneous syndrome of cough, wheeze, dyspnea, and chest
      tightness. However, in a subset of patients, these symptoms may indicate a
      different underlying disease process with variable responsiveness to classic
      asthma therapies. Disease may progress while practitioners attempt conventional
      asthma therapy. Additionally, some types of asthma may require alternative
      approaches to relieve symptoms successfully. This article describes the
      differential diagnosis of asthma and discusses some of the more common asthma
      variants and asthma mimickers. 

PMID- 24286689
TI  - Doc, I can't breathe!

PMID- 24286690
TI  - Influence of repeated dinoprost treatment on ovarian activity in cycling dairy
      cows.
AB  - To study the ovarian response to the long-term effect of PGF2alpha, 16 cows were
      treated with 25 mg tromethamine dinoprost (Pronalgon F; Pfizer, Tokyo, Japan) for
      21 days after natural ovulation. Five control cows were treated with sterile
      physiological saline. The follicle and corpus luteum (CL) development were
      monitored using a real-time ultrasound instrument. In addition, the plasma
      concentration of progesterone (P4) was determined. In nine of the 16 Pronalgon
      treated cows, the first dominant follicle (1st DF), second dominant follicle (2nd
      DF), and third dominant follicle ovulated consecutively (group A). In five cows,
      the 1st and 2nd DFs ovulated consecutively (group B). The developing CL started
      to regress approximately 5 days after each ovulation without maturation in groups
      A and B. In the two remaining Pronalgon-treated cows, there was no further
      ovulation after natural ovulation (group C). In one cow in group C, the 1st DF
      became atretic and the 2nd DF became cystic with the diameter of the cystic
      follicle reaching 31.2 mm on Day 30. In another cow, the 1st DF became cystic
      with a diameter of 30.9 mm on Day 18. Although P4 began to increase after each
      ovulation in all of the Pronalgon-treated cows, it decreased immediately after
      each ovulation without a large increase, peaking at approximately 1 ng/mL.
      Furthermore, the number of days when P4 was >1 ng/mL from natural ovulation to
      Day 21 was 2.6 +/- 0.7 days, which was significantly less than that in the
      control cows (16.0 +/- 0.6 days). These results indicate that the long-term
      effect of PGF2alpha has an important role in ovulation of all dominant follicles
      and might induce cystic ovaries in cows. 

PMID- 24286691
TI  - Biodegradability of pharmaceutical compounds in agricultural soils irrigated with
      treated wastewater.
AB  - Pharmaceutical compounds (PCs) are introduced into agricultural soils via
      irrigation with treated wastewater (TWW). Our data show that carbamazepine,
      lamotrigine, caffeine, metoprolol, sulfamethoxazole and sildenafil are persistent
      in soils when introduced via TWW. However, other PCs, namely diclofenac,
      ibuprofen, bezafibrate, gemfibrozil and naproxen were not detected in soils when
      introduced via TWW. This is likely due to rapid degradation as confirmed in our
      microcosm studies where they exhibited half-lives (t1/2) between 0.2-9.5 days
      when soils were spiked at 50 ng/g soil and between 3 and 68 days when soils were
      spiked at 5000 ng/g soil. The degradation rate and extent of PCs observed in
      microcosm studies were similar in soils that had been previously irrigated with
      TWW or fresh water. This suggests that pre-exposure of the soils to PCs via
      irrigation with TWW does not enhance their biodegradation. This suggests that PCs
      are probably degraded in soils via co-metabolism. 

PMID- 24286692
TI  - Setting ozone critical levels for protecting horticultural Mediterranean crops:
      case study of tomato.
AB  - Seven experiments carried out in Italy and Spain have been used to parameterising
      a stomatal conductance model and establishing exposure- and dose-response
      relationships for yield and quality of tomato with the main goal of setting O3
      critical levels (CLe). CLe with confidence intervals, between brackets, were set
      at an accumulated hourly O3 exposure over 40 nl l(-1), AOT40 = 8.4 (1.2, 15.6)
      ppm h and a phytotoxic ozone dose above a threshold of 6 nmol m(-2) s(-1), POD6 =
      2.7 (0.8, 4.6) mmol m(-2) for yield and AOT40 = 18.7 (8.5, 28.8) ppm h and POD6 =
      4.1 (2.0, 6.2) mmol m(-2) for quality, both indices performing equally well. CLe
      confidence intervals provide information on the quality of the dataset and should
      be included in future calculations of O3 CLe for improving current methodologies.
      These CLe, derived for sensitive tomato cultivars, should not be applied for
      quantifying O3-induced losses at the risk of making important overestimations of
      the economical losses associated with O3 pollution. 

PMID- 24286693
TI  - Tolerance of polar phytoplankton communities to metals.
AB  - Large amounts of pollutants reach polar regions, particularly the Arctic,
      impacting their communities. In this study we analyzed the toxic levels of Hg, Cd
      and Pb to natural phytoplankton communities of the Arctic and Southern Oceans,
      and compared their sensitivities with those observed on phytoplankton natural
      communities from temperate areas. Mercury was the most toxic metal for both
      Arctic and Antarctic communities, while both Cd and Pb were toxic only for the
      Antarctic phytoplankton. Total cell abundance of the populations forming the
      Arctic community increased under high Cd and Pb concentrations, probably due to a
      decrease of the grazing pressure or the increase of the most resistant species,
      although analysis of individual cells indicated that cell death was already
      induced at the highest levels. These results suggest that phytoplankton may have
      acquired adapting mechanisms to face high levels of Pb and Cd in the Arctic
      Ocean. 

PMID- 24286694
TI  - Air pollution and hospital admissions for respiratory diseases in Lanzhou, China.
AB  - Lanzhou is among the most seriously air-polluted cities in China as a whole, due
      to its unique topography, climate, industrial structure and so on. We studied the
      relationship between different air pollution and respiratory hospitalizations
      from 2001 to 2005, the total of respiratory hospital admissions were 28,057. The
      data were analyzed using Poisson regression models after controlling for the long
      time trend for air pollutants, the "day of week" effect and confounding
      meteorological factors. Three air pollutants (PM10, SO2, NO2) had a lag effect,
      the lag was 3-5 days for PM10, 1-3 days for SO2 and 1-4 days for NO2. The
      relative risks were calculated for increases in the inter-quartile range of the
      pollutants (139 MUg/m(3) in PM10, 61 MUg/m(3) in SO2 and 31 MUg/m(3) in NO2).
      Results showed that there were significant associations between air pollutants
      and respiratory hospital admissions, and stronger effects were observed for
      females and aged >=65 yrs in Lanzhou. 

PMID- 24286695
TI  - Pharmaceuticals occurrence in a WWTP with significant industrial contribution and
      its input into the river system.
AB  - Occurrence and removal of 81 representative Pharmaceutical Active Compounds
      (PhACs) were assessed in a municipal WWTP located in a highly industrialized
      area, with partial water reuse after UV tertiary treatment and discharge to a
      Mediterranean river. Water monitoring was performed in an integrated way at
      different points in the WWTP and river along three seasons. Consistent
      differences between therapeutic classes were observed in terms of influent
      concentration, removal efficiencies and seasonal variation. Conventional (primary
      and secondary) treatment was unable to completely remove numerous compounds and
      UV-based tertiary treatment played a complementary role for some of them.
      Industrial activity influence was highlighted in terms of PhACs presence and
      seasonal distribution. Even if global WWTP effluent impact on the studied river
      appeared to be minor, PhACs resulted widespread pollutants in river waters.
      Contamination can be particularly critical in summer in water scarcity areas,
      when water flow decreases considerably. 

PMID- 24286696
TI  - Sorption of phenanthrene and benzene on differently structural kerogen: important
      role of micropore-filling.
AB  - Shale was thermally treated to obtain a series of kerogen with varied maturation.
      Their chemical, structural and porous properties were related to the sorption
      and/or desorption behaviors of phenanthrene and benzene. As the treatment
      temperature increases, aliphatic and carbonyl carbon of the kerogen samples
      decrease, while their aromaticity and maturation increase. Meanwhile, the
      isothermal nonlinearity of phenanthrene and benzene increases whereas the
      sorption capacity and micropore adsorption volumes (Vo,d) initially increase and
      then decrease. The Vo,d of benzene is significantly correlated with, but higher
      than that of phenanthrene, suggesting similar micropore filling mechanism and
      molecular sieve effect. The benzene desorption exhibits hysteresis, which is
      related to the pore deformation of the kerogen and the entrapment of solute in
      the kerogen matrix. The Vo,d of phenanthrene and benzene on the kerogen samples
      accounts for 23-46% and 36-65% of the maximum sorption volumes, respectively,
      displaying the importance of the micropore filling. 

PMID- 24286697
TI  - Different toxicity mechanisms between bare and polymer-coated copper oxide
      nanoparticles in Lemna gibba.
AB  - In this report, we investigated how the presence of a polymer shell (poly(styrene
      co-butyl acrylate) alters the toxicity of CuO NPs in Lemna gibba. Based on total
      Cu concentration, core-shell CuO NPs were 10 times more toxic than CuO NPs,
      inducing a 50% decrease of growth rate at 0.4 g l(-1) after 48-h of exposure
      while a concentration of 4.5 g l(-1) was required for CuO NPs for a similar
      effect. Toxicity of CuO NPs was mainly due to NPs solubilization in the media.
      Based on the accumulated copper content in the plants, core-shell CuO NPs induced
      4 times more reactive oxygen species compared to CuO NPs and copper sulfate,
      indicating that the presence of the polymer shell changed the toxic effect
      induced in L. gibba. This effect could not be attributed to the polymer alone and
      reveals that surface modification may change the nature of NPs toxicity. 

PMID- 24286698
TI  - The functional and morphological characteristics of sciatic nerve degeneration
      and regeneration after crush injury in rats.
AB  - BACKGROUND: Peripheral nerve damage induces a sequence of degeneration and
      regeneration events with a specific time course that leads to (partial)
      functional recovery. Quantitative electrophysiological analysis of degeneration
      and recovery over time is essential to understand the process. NEW METHOD: The
      presented ex vivo neurophysiological method evaluates functional recovery of the
      propagation of the compound action potential after crush injury of the rat
      sciatic nerve. A 32 channel electrode array was used to monitor compound action
      potential propagation at time points between 1h and 35 days after semi
      quantitative crush injury of the rat sciatic nerve. RESULTS: The compound action
      potential was characterized by four measures: the latency, the duration, the
      amplitude and a measure that combined time and location. These four parameters
      reflected the subsequent steps in early axonal degradation, the transition to
      rapid degeneration followed by sprouting and the long period of remyelination
      that accompanied regeneration. COMPARISON WITH EXISTING METHODS: The
      neurophysiology measures of the compound action potential were compared with the
      morphology of the nerve at representative time points and analysis of functional
      recovery of action potential propagation was compared with a behavioral test: the
      foot flick test. CONCLUSIONS: Our data suggests that the ex vivo
      electrophysiological method is complementary to the classical behavioral foot
      flick test in that it allows a detailed time analysis of the degeneration and
      early regeneration phases at a high spatial and temporal sensitivity. The results
      were well-matched with observations made with immunohistochemical and
      morphological methods.

PMID- 24286699
TI  - Multi-unit recording with iridium oxide modified stereotrodes in Drosophila
      melanogaster.
AB  - BACKGROUND: Drosophila is a very favorable animal model for the studies of
      neuroscience. However, it remains a great challenge to employ
      electrophysiological approaches in Drosophila to study the neuronal assembly
      dynamics in vivo, partially due to the small size of the Drosophila brain. Small
      and sensitive microelectrodes for multi-unit recordings are greatly desired. NEW
      METHOD: We fabricated micro-scale stereotrodes for electrical recordings in
      Drosophila melanogaster. The stereotrodes were modified with iridium oxide (IrO2)
      under a highly controllable deposition procedure to improve their electrochemical
      properties. Electrical recordings were carried out using the IrO2 stereotrodes to
      detect spontaneous action potentials and LFPs in vivo. RESULTS: The IrO2
      electrodes exhibited significantly higher capacitance and lower impedance at 1
      kHz. Electrical recording with the IrO2 stereotrodes in vivo demonstrated an
      average signal-to-noise ratio (SNR) of 7.3 and a significantly improved LFP
      sensitivity. 5 types of different neurons recorded were clearly separated.
      Electrophysiological responses to visual and odor stimulation were also detected,
      respectively. COMPARISON WITH EXISTING METHOD(S): The most widely used electrodes
      for electrical recording in Drosophila are glass microelectrode and sharpened
      tungsten microelectrode, which are typically used for single-unit recordings.
      Although tetrode technology has been used to record multi-neuronal activities
      from Drosophila, the fabricated IrO2 stereotrodes possess smaller geometry size
      but exhibited comparable recording signal-to noise ration and better sorting
      quality. CONCLUSIONS: The IrO2 stereotrodes are capable to meet the requirements
      of multi-unit recording and spike sorting, which will be a useful tool for the
      electrophysiology-based researches especially in Drosophila and other small
      animals.

PMID- 24286700
TI  - Machine learning on brain MRI data for differential diagnosis of Parkinson's
      disease and Progressive Supranuclear Palsy.
AB  - BACKGROUND: Supervised machine learning has been proposed as a revolutionary
      approach for identifying sensitive medical image biomarkers (or combination of
      them) allowing for automatic diagnosis of individual subjects. The aim of this
      work was to assess the feasibility of a supervised machine learning algorithm for
      the assisted diagnosis of patients with clinically diagnosed Parkinson's disease
      (PD) and Progressive Supranuclear Palsy (PSP). METHOD: Morphological T1-weighted
      Magnetic Resonance Images (MRIs) of PD patients (28), PSP patients (28) and
      healthy control subjects (28) were used by a supervised machine learning
      algorithm based on the combination of Principal Components Analysis as feature
      extraction technique and on Support Vector Machines as classification algorithm.
      The algorithm was able to obtain voxel-based morphological biomarkers of PD and
      PSP. RESULTS: The algorithm allowed individual diagnosis of PD versus controls,
      PSP versus controls and PSP versus PD with an Accuracy, Specificity and
      Sensitivity>90%. Voxels influencing classification between PD and PSP patients
      involved midbrain, pons, corpus callosum and thalamus, four critical regions
      known to be strongly involved in the pathophysiological mechanisms of PSP.
      COMPARISON WITH EXISTING METHODS: Classification accuracy of individual PSP
      patients was consistent with previous manual morphological metrics and with other
      supervised machine learning application to MRI data, whereas accuracy in the
      detection of individual PD patients was significantly higher with our
      classification method. CONCLUSIONS: The algorithm provides excellent
      discrimination of PD patients from PSP patients at an individual level, thus
      encouraging the application of computer-based diagnosis in clinical practice.

PMID- 24286701
TI  - StimSync: open-source hardware for behavioral and MRI experiments.
AB  - BACKGROUND: Many neuroscience experiments rely on presenting stimuli and
      measuring participants' responses to these events. Often computer screens,
      speakers and keyboards are sufficient. However, these devices are not appropriate
      for some situations. For example, some studies present tactile or olfactory
      stimuli or brain stimulation. Likewise, keyboard buttons are not appropriate for
      use with vocal responses, small animals or individuals with motor impairments.
      NEW METHOD: We describe StimSync, which simulates USB keyboard inputs, allowing
      use with most experimental software. StimSync can measure button presses, optical
      signals from magnetic resonance imaging systems, changes in ambient light (e.g.
      synchronizing intracranial electrography), and auditory events (a voice key). In
      addition to the USB keyboard mode (necessarily millisecond precision), StimSync
      can also be set to provide higher precision timing. This feature can be used to
      validate timing, ensuring event synchronization (e.g. auditory events, visual
      events, brain stimulation). In addition to recording inputs, StimSync provides
      seven digital outputs for controlling external devices. Finally, StimSync can
      record analog inputs; we illustrate how this can be used to evaluate the rise
      time for computer displays. RESULTS: We observed outputs with a mean latency of
      2.1ms (sd=0.17ms) and USB inputs with a mean latency of 2ms (sd=0.54ms).
      COMPARISON WITH EXISTING METHOD(S): StimSync statistically outperforms two
      professional solutions and numerically outperforms other devices described in the
      literature. CONCLUSIONS: StimSync
      (http://www.mccauslandcenter.sc.edu/CRNL/tools/stimsync) provides an open-source
      solution for controlling and validating neuroscience experiments. In addition to
      sharing the design, we have produced a batch of devices to demonstrate the market
      for professional implementations.

PMID- 24286702
TI  - Does a location predilection exist for warfarin associated intracerebral
      hemorrhage?

PMID- 24286703
TI  - Warfarin therapy and predilection for infratentorial hemorrhage.

PMID- 24286705
TI  - Agreement between DSM-IV and ICD-10 criteria for opioid use disorders in two
      Iranian samples.
AB  - The aim of this study was to determine the agreement between the two systems in
      opioid users in the general population and a clinical sample. Two series of data
      were used in this study. The first was the data of 236 home-residing opioid
      abusers aged 15-64, who had previously participated in the Iran Mental Health
      Survey (IranMHS) in 2011, and the second was the data of 104 general psychiatry
      patients from inpatient or outpatient wards of two psychiatry hospitals in
      Tehran. Opioid use disorders were evaluated with CIDI-version 2.1. The disorders
      were assessed in all participants who used opioid substances for at least 5 times
      during the past 12months. In the sample from the general population, the
      agreement between the two systems on the diagnosis of dependence was excellent
      (0.81). The agreement between the two systems on the diagnosis of abuse and
      harmful use was 0.41. In the clinical sample, the agreement between the two
      systems on the diagnosis of dependence or any opioid use disorder was 0.96 and
      0.93, respectively. The agreement between abuse and harmful use was 0.9 and -0.02
      with and without regarding hierarchy, respectively. The inter-rater reliability
      of both DSM-IV and ICD-10 systems for all diagnosis was more than 0.95. The
      results of the diagnosis of dependence in the two systems had a weak concordance
      with treatment. The diagnostic criteria of DSM-IV and ICD-10 regarding dependence
      are very similar and the diagnosis produced by each system is concordant with the
      other system. However, the two systems have noticeable discrepancies in the
      diagnosis of abuse and harmful use. The discrepancies result from their
      conceptual differences and necessitate further revision in the definition of
      these disorders in the two systems. 

PMID- 24286704
TI  - Sex differences in impulsive action and impulsive choice.
AB  - Here, we review the evidence for sex differences in behavioral measures of
      impulsivity for both humans and laboratory animals. We focus on two specific
      components of impulsivity: impulsive action (i.e., difficulty inhibiting a
      prepotent response) and impulsive choice (i.e., difficulty delaying
      gratification). Sex differences appear to exist on these measures, but the
      direction and magnitude of the differences vary. In laboratory animals, impulsive
      action is typically greater in males than females, whereas impulsive choice is
      typically greater in females. In humans, women discount more steeply than men,
      but sex differences on measures of impulsive action depend on tasks and subject
      samples. We discuss implications of these findings as they relate to drug
      addiction. We also point out the major gaps in this research to date, including
      the lack of studies designed specifically to examine sex differences in
      behavioral impulsivity, and the lack of consideration of menstrual or estrous
      phase or sex hormone levels in the studies. 

PMID- 24286706
TI  - Protracted impairment of impulse control under an acute dose of alcohol: a time
      course analysis.
AB  - Alcohol is well-known for impairing impulse control as well as its disruptive
      effects on other aspects of behavioral functioning, such as motor control. Time
      course analyses during a single dose show rapid development of acute tolerance to
      impairment of motor coordination, reaction time, and levels of subjective
      intoxication, but no acute tolerance to impairment of the ability to inhibit
      responses. Evidence for a possible lag in tolerance development to the impairing
      effects of alcohol on inhibitory control suggests that, as drinkers' blood
      alcohol concentration (BAC) declines, they might exhibit prolonged impulsivity
      despite having an unimpaired ability to initiate action. The present study
      extended the time-course analysis to examine the recovery of inhibitory control
      under a dose of alcohol as drinkers' BAC descended from a peak of 80 mg/100ml to
      a zero level. Twenty-four healthy adults were tested following 0.65 g/kg alcohol
      and a placebo in a counterbalanced order. They performed a cued go/no-go task
      that measured response inhibition. They also performed tasks that assessed
      reaction time, motor coordination, and completed ratings of their subjective
      levels of intoxication. Alcohol initially impaired inhibitory control, response
      time, and motor coordination and increased subjective ratings of intoxication.
      However, acute tolerance to the impairing effects of alcohol was observed for
      measures of response time, motor coordination, and ratings of intoxication and
      these measures returned to sober (i.e., placebo) levels by the time BAC fell to
      near zero. By contrast, impairment of inhibitory control showed no acute
      tolerance and remained impaired even when drinkers' BAC returned to near zero.
      Taken together, these results indicate that the disinhibiting effects of alcohol
      are present even when the impairing effects of alcohol on other aspects of
      behavior have diminished under the dose. These findings could provide a greater
      understanding of impulsive behaviors during the descending limb of intoxication.

PMID- 24286707
TI  - Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase
      increases atherosclerotic plaque vulnerability in mice.
AB  - The role of endocannabinoids such as anandamide during atherogenesis remains
      largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in
      anandamide degradation, and its inhibition is associated with subsequent higher
      levels of anandamide. Here, we tested whether selective inhibition of FAAH
      influences the progression of atherosclerosis in mice. Selective inhibition of
      FAAH using URB597 resulted in significantly increased plasma levels of anandamide
      compared to control, as assessed by mass spectrometry experiments in mice.
      Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich
      diet to induce atherosclerotic conditions. Simultaneously, mice received either
      the pharmacological FAAH inhibitor URB597 1mg/kg body weight (n=28) or vehicle
      (n=25) via intraperitoneal injection three times a week. After eight weeks, mice
      were sacrificed, and experiments were performed. Vascular superoxide generation
      did not differ between both groups, as measured by L012 assay. To determine
      whether selective inhibition of FAAH affects atherosclerotic plaque inflammation,
      immunohistochemical staining of the aortic root was performed. Atherosclerotic
      plaque formation, vascular macrophage accumulation, as well as vascular T cell
      infiltration did not differ between both groups. Interestingly, neutrophil cell
      accumulation was significantly increased in mice receiving URB597 compared to
      control. Vascular collagen structures in atherosclerotic plaques were
      significantly diminished in mice treated with URB597 compared to control, as
      assessed by picro-sirius-red staining. This was accompanied by an increased
      aortic expression of matrix metalloproteinase-9, as determined by quantitative RT
      PCR and western blot analysis. Inhibition of fatty acid amide hydrolase does not
      influence plaque size but increases plaque vulnerability in mice. 

PMID- 24286708
TI  - Statins and the nursing home.

PMID- 24286709
TI  - How can we increase seasonal influenza vaccine coverage in nursing home
      residents?

PMID- 24286710
TI  - Clinical update on nursing home medicine: 2013.
AB  - This is the seventh article in the series of Clinical Updates on Nursing Home
      Care. The topics covered are antiresorptive drugs, hip fracture, hypertension,
      orthostatic hypotension, depression, undernutrition, anorexia, cachexia,
      sarcopenia, exercise, pain, and behavioral and psychological symptoms of
      dementia. 

PMID- 24286711
TI  - Signs and symptoms indicative of potential adverse drug reactions in homecare
      patients.
AB  - PURPOSE: The purpose of this study was to determine whether homecare workers can
      detect signs and symptoms indicative of potential adverse drug reactions (ADRs)
      in homecare patients, using a standardized observation list. METHODS: This
      observational study involved 115 patients cared for by 2 homecare organizations
      in The Netherlands between April 2011 and August 2011. During routine home
      visits, homecare workers filled out a standardized observation list of signs and
      symptoms indicative of potential ADRs, namely, gastrointestinal and other
      bleedings, electrolyte disturbances, renal and heart failure, digoxin
      intoxication, constipation, disturbances of diabetic control, and falls. Their
      observations were compared against the medications that the patients were using
      and their known side effects, by a panel of clinical pharmacology experts.
      Sensitivity, specificity, and positive and negative predicted values of the
      standardized observations were calculated. RESULTS: In total, 234 signs and
      symptoms indicative of potential ADRs were observed by the homecare workers, 116
      (49.6%) of which were considered drug related. More than one-half of the observed
      signs of gastrointestinal bleeding could be considered as drug related. Observed
      dizziness (64.1%) and drowsiness (53.3%) could be drug related in most cases, as
      could most cases (71.4%) of fainting spells (indicative of renal or heart
      failure). Seventeen of 20 observed falls could be drug related. The specificity
      of the standardized observation list was high, varying from 0.70 (confidence
      interval 0.62-0.77) to 0.97 (confidence interval 0.95-0.98). CONCLUSIONS: Signs
      and symptoms indicative of potential ADRs recorded by homecare workers using a
      standardized observation list can aid in the early recognition of ADRs in
      homecare patients.

PMID- 24286712
TI  - The unique functions of tissue-specific proteasomes.
AB  - The 26S proteasome is the main protease in eukaryotes. Proteolysis occurs within
      the cylindrical 20S proteasome that is constitutively expressed in most tissues.
      However, three tissue-specific versions of the 20S proteasome have been
      discovered to date. The immunoproteasome is optimized to process antigens and it
      directs the differentiation of T helper (Th) cells. The thymoproteasome is
      selectively expressed in cortical epithelial cells of the thymus where it plays
      an essential role in the positive selection of T lymphocytes. Finally, the
      spermatoproteasome is found in the testes where it is required during
      spermatogenesis. Here, we outline how tissue-specific proteasomes adapt to
      functional needs in their respective tissues and how their selective inhibition
      may be used to interfere with autoimmune diseases and cancer. 

PMID- 24286713
TI  - The neglected lead on electrocardiogram: T wave inversion in lead aVL,
      nonspecific finding or a sign for left anterior descending artery lesion?
AB  - BACKGROUND: The electrocardiogram (ECG) is the most important diagnostic tool for
      acute myocardial infarction (AMI). T wave inversion (TWI) in lead aVL has not
      been emphasized or well recognized. OBJECTIVE: This study examined the
      relationship between the presence of TWI before the event and mid-segment left
      anterior descending (MLAD) artery lesion in patients with AMI. METHODS:
      Retrospective charts of patients with acute coronary syndrome between the months
      of January 2009 and December 2011 were reviewed. All patients with MLAD lesion
      were identified and their ECG reviewed for TWI in lead aVL. RESULTS: Coronary
      angiography was done on 431 patients. Of these, 125 (29%) had an MLAD lesion. One
      hundred and six patients (84.8%) had a lesion > 50% and 19 patients (15.2%) had a
      lesion < 50%. Of the 106 patients who had a MLAD lesion > 50%, 90 patients
      (84.9%) had TWI in lead aVL and one additional lead. Of the 19 patients who had
      an MLAD lesion < 50%, 8 patients (42.1%) had TWI in lead aVL and one additional
      lead. Isolated TWI in lead aVL had an overall sensitivity of 76.7% (95%
      confidence interval [CI] 0.65-0.86), a specificity of 71.4% (95% CI 0.45-0.88), a
      positive predictive value of 92%, a negative predictive value of 41.7%, a
      positive likelihood ratio of 2.7 (95% CI 1.16-6.22), and negative likelihood
      ratio of 0.32 (95% CI 0.19-0.58) for predicting a MLAD lesion of > 50% (p =
      0.0011). CONCLUSIONS: TWI in lead aVL might signify a mid-segment LAD lesion.
      Recognition of this finding and early appropriate referral to a cardiologist
      might be beneficial. Additional studies are needed to validate this finding.

PMID- 24286714
TI  - Integration of palliative care into emergency medicine: the Improving Palliative
      Care in Emergency Medicine (IPAL-EM) collaboration.
AB  - BACKGROUND: Emergency department (ED) providers commonly care for seriously ill
      patients who suffer from advanced, chronic, life-limiting illnesses in addition
      to those that are acutely ill or injured. Both the chronically ill and those who
      present in extremis may benefit from application of palliative care principles.
      CASE REPORT: We present a case highlighting the opportunities and need for better
      integration of emergency medicine and palliative care. DISCUSSION: We offer
      practical guidelines to the ED faculty/administrators who seek to enhance the
      quality of patient care in their own unique ED setting by starting an initiative
      that better integrates palliative principles into daily practice. Specifically,
      we outline four things to do to jumpstart this collaborative effort. CONCLUSION:
      The Improving Palliative Care in Emergency Medicine project sponsored by the
      Center to Advance Palliative Care is a resource that assists ED health care
      providers with the process and structure needed to integrate palliative care into
      the ED setting.

PMID- 24286715
TI  - Acute lobar nephronia: a case report and literature review.
AB  - BACKGROUND: Patients with fever, vomiting, and abdominal pain commonly present to
      the emergency department, often generating a broad differential diagnosis. We
      describe the first reported case in the emergency medicine literature of acute
      lobar nephronia (ALN). OBJECTIVES: To describe the presentation, evaluation, and
      management of acute lobar nephronia. CASE REPORT: A healthy 27-year-old woman
      presented after 18 h of fever to 39.94 degrees C (103.9 degrees F), nausea,
      vomiting, and severe right-sided abdominal pain. Despite a normal urinalysis, a
      contrasted computed tomography scan of the abdomen and pelvis demonstrated right
      perinephric stranding, which was initially interpreted as pyelonephritis. A staff
      over-read the following day by a radiology body specialist confirmed "likely
      developing abscess," consistent with the diagnosis of acute lobar nephronia.
      CONCLUSION: A normal urinalysis may move clinicians to dismiss a nephrogenic or
      urologic process. ALN is considered a midpoint in the spectrum of upper urinary
      tract infections between acute pyelonephritis and intrarenal abscess. Diagnosis
      may be difficult, and inpatient management, sometimes prolonged, is the norm.

PMID- 24286716
TI  - A cis-element responsible for cGMP in the promoter of the soybean chalcone
      synthase gene.
AB  - The cyclic nucleotides cGMP and cAMP have been reported to play key roles in the
      regulation of plant processes and responses. We have previously reported that
      several genes encoding flavonoid biosynthetic enzymes, including chalcone
      synthase (CHS) in soybean (Glycine max L.), were induced by cGMP but not cAMP.
      The soybean genome contains nine CHS gene copies (GmCHS1-9). We investigated the
      responsiveness of several GmCHS genes to cGMP, cAMP, NO, and white light.
      Quantitative RT-PCR analysis showed that the transcript levels of GmCHS7 and
      GmCHS8 were increased by 3.6- and 3.8-fold, respectively, with cGMP whereas the
      transcript levels of GmCHS2 remained constant. Although cAMP had no effect on the
      transcript levels of the three genes, NO had an activation effect on all three.
      White light activated the three genes in a transient manner, with GmCHS2, GmCHS7,
      and GmCHS8 transcript levels increasing 3-fold after 3 h and decreasing to basal
      levels after 9 h. The GmCHS8 promoter contains several important cis-elements,
      including the G-box and H-box forming the Unit-I-like sequence and the MYB
      binding sequence, a target of the GmMYB176 transcription factor regulating the
      expression of GmCHS8. A transient gene expression assay revealed the activation
      of the Unit-I-like sequence, but not of the MYB binding sequence, by cGMP. The
      combination of G-box and H-box was necessary for cGMP responsiveness. Taken
      together, these results suggest that the Unit-I-like sequence in the promoters of
      GmCHS7 and GmCHS8 is a cGMP responsive cis-element in these genes and that NO
      exerts its effect via cis-elements other than the Unit-I-like sequence.

PMID- 24286717
TI  - Adenine deaminase is encoded by Tad1 and participates in copper accumulation in
      Trichoderma reesei.
AB  - We cloned a novel Tad1 gene and demonstrated that this gene is closely involved
      in copper bioaccumulation in Trichoderma reesei. Tad1 gene encodes a 510 amino
      acids protein of the amidohydrolase superfamily which belongs to COG0402. We
      found that adenine was the most efficient substrate of Tad1 protein among the
      substrates used in this study. Gene function was also investigated by
      overexpression and RNA interference. Results showed that copper accumulation
      increased in mutant cells when Tad1 was overexpressed; by contrast, copper
      accumulation significantly decreased when Tad1 was inhibited. To investigate the
      function of Tad1 in copper bioaccumulation, we determined adenine, hypoxanthine,
      and xanthine concentrations by reversed phase HPLC. Tad1 overexpression induced a
      substantial production of xanthine, which functions in binding numerous copper
      ions and reducing copper concentration. We further compared the gene expression
      profile of AT01 with that of a wild-type T. reesei strain grown in a medium
      containing 1.0mM Cu(2+) by performing DNA microarray. Several upregulated genes
      in the mutant were associated with adenine or copper metabolism. 

PMID- 24286718
TI  - Modelling language evolution: Examples and predictions.
AB  - We survey recent computer modelling research of language evolution, focusing on a
      rule-based model simulating the lexicon-syntax coevolution and an equation-based
      model quantifying the language competition dynamics. We discuss four predictions
      of these models: (a) correlation between domain-general abilities (e.g.
      sequential learning) and language-specific mechanisms (e.g. word order
      processing); (b) coevolution of language and relevant competences (e.g. joint
      attention); (c) effects of cultural transmission and social structure on
      linguistic understandability; and (d) commonalities between linguistic,
      biological, and physical phenomena. All these contribute significantly to our
      understanding of the evolutions of language structures, individual learning
      mechanisms, and relevant biological and socio-cultural factors. We conclude the
      survey by highlighting three future directions of modelling studies of language
      evolution: (a) adopting experimental approaches for model evaluation; (b)
      consolidating empirical foundations of models; and (c) multi-disciplinary
      collaboration among modelling, linguistics, and other relevant disciplines. 

PMID- 24286719
TI  - Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic
      and eukaryotic immune systems.
AB  - Recent evidence supports that prokaryotes exhibit adaptive immunity in the form
      of CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) and Cas
      (CRISPR associated proteins). The CRISPR-Cas system confers resistance to
      exogenous genetic elements such as phages and plasmids by allowing for the
      recognition and silencing of these genetic elements. Moreover, CRISPR-Cas serves
      as a memory of past exposures. This suggests that the evolution of the immune
      system has counterparts among the prokaryotes, not exclusively among eukaryotes.
      Mathematical models have been proposed which simulate the evolutionary patterns
      of CRISPR, however large gaps in our understanding of CRISPR-Cas function and
      evolution still exist. The CRISPR-Cas system is analogous to small RNAs involved
      in resistance mechanisms throughout the tree of life, and a deeper understanding
      of the evolution of small RNA pathways is necessary before the relationship
      between these convergent systems is to be determined. Presented in this review
      are novel RNAi therapies based on CRISPR-Cas analogs and the potential for future
      therapies based on CRISPR-Cas system components. 

PMID- 24286720
TI  - Effects of gender on sympathovagal imbalance, prehypertension status, and
      cardiovascular risks in first-degree relatives of type 2 diabetics.
AB  - BACKGROUND: Although cardiovascular (CV) risks are reported in first-degree
      relatives (FDRs) of type 2 diabetics, effects of gender on sympathovagal
      imbalance (SVI) and CV risks in these subjects have not been investigated.
      METHODS: Body mass index (BMI), blood pressure variability parameters including
      baroreflex sensitivity (BRS), spectral indices of heart rate variability,
      autonomic function tests, insulin resistance, lipid profile, inflammatory markers
      (interleukin 6, high-sensitivity C-reactive protein, tumor necrosis factor alpha)
      and oxidative stress (OS) marker were measured and analyzed in control group
      (without family history of diabetes; 65 women, 60 men) and study group (FDRs of
      type 2 diabetics; 52 women, 49 men) subjects. RESULTS: BMI, heart rate, blood
      pressure, rate-pressure product, stroke volume, left-ventricular ejection time,
      cardiac output, total peripheral resistance, homeostatic model of insulin
      resistance, lipid profile, inflammatory and OS markers, and ratio of low
      frequency to high-frequency power of heart rate variability (LF-HF ratio), a
      sensitive marker of SVI, were significantly increased, and BRS was significantly
      decreased in study group men compared with women. SVI was more intense in men and
      was due to concomitant sympathetic activation and vagal inhibition. There was no
      SVI in control subjects. Multiple regression analysis demonstrated independent
      contribution of BMI, homeostatic model of insulin resistance, atherogenic index,
      inflammatory and OS markers, and BRS to LF-HF ratio. Logistic regression analysis
      demonstrated significant prediction of prehypertension status and rate-pressure
      product (markers of CV risk) by LF-HF, which was more prominent in men.
      CONCLUSIONS: SVI is more intense in male FDRs of type 2 diabetics, and SVI is
      associated with increased CV risk due to insulin resistance, dyslipidemia,
      inflammation, and oxidative stress in these subjects.

PMID- 24286721
TI  - Influence of urban morphology on total noise pollution: multifractal description.
AB  - Exposure to ambient noise levels above 65 dB can cause public health problems.
      The spatial distribution of this kind of pollution is linked to various elements
      which make up the urban form, such as construction density, the existence of open
      spaces and the shape and physical position of buildings. Since urban morphology
      displays multifractal behaviour, the present research studies for the first time
      the relationship between total noise pollution and urban features, such as street
      width and building height by means of a joint multifractal spectrum in two
      neighbourhoods of the city of Cordoba (Andalusia, Spain). According to the
      results, the joint multifractal spectrum reveals a positive correlation between
      the total noise pollution and the street width to building height ratio, this
      being more evident when urban morphology is regular. The information provided by
      the multifractal analysis completes the description obtained by using urban
      indexes and landscape metrics and might be useful for urban planning once the
      linkage between both frameworks has been done.

PMID- 24286722
TI  - A theory-based computer mediated communication intervention to promote mental
      health and reduce high-risk behaviors in the LGBT population.
AB  - The Healthy People 2020 (2012) report has identified that isolation, lack of
      social services, and a shortage of culturally competent providers serve as
      barriers to the health of lesbian, gay, bisexual, and transgender (LGBT)
      individuals who have HIV/AIDS. Self-transcendence theory proposes that
      individuals who face increased vulnerability or mortality may acquire an
      increased capacity for self-transcendence and its positive influence on mental
      health and well-being. The use of technology-enabled social and community support
      and group interventions through computer mediated self-help (CMSH) with LGBT
      individuals may help meet mental health needs of this group, and support healthy
      lifestyle practices. This article presents an overview of steps taken to propose
      a theory-based CMSH intervention for testing in research and eventual application
      in practice. 

PMID- 24286723
TI  - Out of the alps: the biogeography of a disjunctly distributed mountain butterfly,
      the almond-eyed ringlet Erebia alberganus (Lepidoptera, Satyrinae).
AB  - Many studies on the biogeography of thermophilic and arctic-alpine species were
      performed during the past. Only little is known about species with intermediate
      characteristics. We analyzed the molecular biogeography of the butterfly Erebia
      alberganus (30 populations, representing 1106 individuals), sampled over the
      Alps, Apennines (Italy), and the Stara Planina (Bulgaria) using allozyme
      electrophoresis (17 loci). Genetic analyses revealed 3 major splits, with the
      strongest between the Stara Planina populations and all other populations, and a
      weaker split between the Alps and the Apennines. Individuals from the Apennines
      were genetically nested within the Alps group. The Alps cluster was segregated
      into 3 groups: the Southwestern, Western/Central, and Eastern Alps. The genetic
      diversities were highest for the Alps populations and significantly lower in the
      2 isolates (Apennines, Stara Planina). The remarkable genetic split between Stara
      Planina and all other populations and the genetic distinctiveness of the former
      cluster might be interpreted as an ancient colonization event of this Balkan
      mountain range. The Apennines populations derive from a more recent expansion out
      of the Southwestern Alps. After surviving the Wurm ice age most probably in the
      central Apennines, accompanied by genetic modification of some of these
      populations, northward expansion might have started from the western parts of the
      central Apennines reaching the northern Apennines during the early postglacial.
      The subtle genetic differentiation found among the Alps populations probably
      reflects 3 geographically disjunct Wurm glacial centers located at the western
      slopes of the Southwestern Alps, at the southern slopes of the Central Alps, and
      in the Southeastern Alps. 

PMID- 24286725
TI  - Evidence-based approach to medical and surgical treatment of nasal polyposis.

PMID- 24286727
TI  - Computer simulation of MHD blood conveying gold nanoparticles as a third grade
      non-Newtonian nanofluid in a hollow porous vessel.
AB  - In this paper, heat transfer and flow analysis for a non-Newtonian third grade
      nanofluid flow in porous medium of a hollow vessel in presence of magnetic field
      are simulated analytically and numerically. Blood is considered as the base third
      grade non-Newtonian fluid and gold (Au) as nanoparticles are added to it. The
      viscosity of nanofluid is considered a function of temperature as Vogel's model.
      Least Square Method (LSM), Galerkin method (GM) and fourth-order Runge-Kutta
      numerical method (NUM) are used to solve the present problem. The influences of
      the some physical parameters such as Brownian motion and thermophoresis
      parameters on non-dimensional velocity and temperature profiles are considered.
      The results show that increasing the thermophoresis parameter (N(t)) caused an
      increase in temperature values in whole domain and an increase in nanoparticles
      concentration just near the inner wall of vessel. Furthermore by increasing the
      MHD parameter, velocity profiles decreased due to magnetic field effect.

PMID- 24286726
TI  - Tumor necrosis factor alpha (TNF-alpha) receptor-I is required for TNF-alpha
      mediated fulminant virus hepatitis caused by murine hepatitis virus strain-3
      infection.
AB  - TNF-alpha plays an essential role in the pathogenesis of fulminant virus
      hepatitis (FH) caused by infection with murine hepatitis virus strain-3 (MHV-3).
      However, the specific TNF-alpha receptors (TNFR) involved in this disease and how
      they mediate this effect are uncertain. Here, we showed that the expression of
      TNFR1 and TNFR2 in the liver and spleen was triggered by MHV-3. However, only
      TNFR1(-/-) mice were resistant to MHV-3 mediated FH, as displayed by a dramatic
      decrease in tissue necrosis and cell apoptosis in the infected spleens and livers
      from TNFR1(-/-) mice, as well as prolonged survival in these mice compared to
      wild type littermate controls. Mechanistically, TNFR1 deficiency directly impeded
      the serum and tissue levels of fibrinogen-like protein 2 (FGL2), a virus-induced
      procoagulant molecule that promotes cell apoptosis. Additionally, the expression
      of apoptosis-associated molecules, Fas and Fas ligand (FasL) in the infected
      organs from TNFR1(-/-) mice were also decreased. Moreover, the infiltration of
      neutrophils rather than Foxp3(+) regulatory T cells, which produce
      proinflammatory factors and FGL2 directly, into the infected liver and spleen
      tissues was also decreased in TNFR1(-/-) mice. These combined results indicate
      that signaling through TNFR1 plays an essential role in the pathogenesis of FH
      caused by MHV-3 infection, and interruption of this signaling pathway could be
      useful for clinical therapy. 

PMID- 24286728
TI  - ORTH: R and SAS software for regression models of correlated binary data based on
      orthogonalized residuals and alternating logistic regressions.
AB  - This article describes a new software for modeling correlated binary data based
      on orthogonalized residuals, a recently developed estimating equations approach
      that includes, as a special case, alternating logistic regressions. The software
      is flexible with respect to fitting in that the user can choose estimating
      equations for association models based on alternating logistic regressions or
      orthogonalized residuals, the latter choice providing a non-diagonal working
      covariance matrix for second moment parameters providing potentially greater
      efficiency. Regression diagnostics based on this method are also implemented in
      the software. The mathematical background is briefly reviewed and the software is
      applied to medical data sets. 

PMID- 24286730
TI  - NHS England launches consultation on improving general practice in London.

PMID- 24286729
TI  - Breast density classification to reduce false positives in CADe systems.
AB  - This paper describes a novel weighted voting tree classification scheme for
      breast density classification. Breast parenchymal density is an important risk
      factor in breast cancer. Moreover, it is known that mammogram interpretation is
      more difficult when dense tissue is involved. Therefore, automated breast density
      classification may aid in breast lesion detection and analysis. Several
      classification methods have been compared and a novel hierarchical classification
      procedure of combined classifiers with linear discriminant analysis (LDA) is
      proposed as the best solution to classify the mammograms into the four BIRADS
      tissue classes. The classification scheme is based on 298 texture features.
      Statistical analysis to test the normality and homoscedasticity of the data was
      carried out for feature selection. Thus, only features that are influenced by the
      tissue type were considered. The novel classification techniques have been
      incorporated into a CADe system to drive the detection algorithms and tested with
      1459 images. The results obtained on the 322 screen-film mammograms (SFM) of the
      mini-MIAS dataset show that 99.75% of samples were correctly classified. On the
      1137 full-field digital mammograms (FFDM) dataset results show 91.58% agreement.
      The results of the lesion detection algorithms were obtained from modules
      integrated within the CADe system developed by the authors and show that using
      breast tissue classification prior to lesion detection leads to an improvement of
      the detection results. The tools enhance the detectability of lesions and they
      are able to distinguish their local attenuation without local tissue density
      constraints. 

PMID- 24286731
TI  - The Natural Hospital Environment: a Socio-Technical-Material perspective.
AB  - OBJECTIVES: This paper introduces two concepts into analyses of information
      security and hospital-based information systems-- a Socio-Technical-Material
      theoretical framework and the Natural Hospital Environment. METHOD: The research
      is grounded in a review of pertinent literature with previously published
      Australian (Victoria) case study data to analyse the way clinicians work with
      privacy and security in their work. The analysis was sorted into thematic
      categories, providing the basis for the Natural Hospital Environment and Socio
      Technical-Material framework theories discussed here. RESULTS: Natural Hospital
      Environments feature inadequate yet pervasive computer use, aural privacy
      shortcomings, shared workspace, meagre budgets, complex regulation that hinders
      training outcomes and out-dated infrastructure and are highly interruptive.
      DISCUSSION: Working collaboratively in many cases, participants found ways to
      avoid or misuse security tools, such as passwords or screensavers for patient
      care. Workgroup infrastructure was old, architecturally limited, haphazard in
      some instances, and was less useful than paper handover sheets to ensure the
      quality of patient care outcomes. Despite valiant efforts by some participants,
      they were unable to control factors influencing the privacy of patient health
      information in public hospital settings. CONCLUSION: Future improvements to
      hospital-based organisational frameworks for e-health can only be made when there
      is an improved understanding of the Socio-Technical-Material theoretical
      framework and Natural Hospital Environment contexts. Aspects within control of
      clinicians and administrators can be addressed directly although some others are
      beyond their control. An understanding and acknowledgement of these issues will
      benefit the management and planning of improved and secure hospital settings.

PMID- 24286732
TI  - Awareness of diabetic retinopathy is the key step for early prevention, diagnosis
      and treatment of this disease in China.

PMID- 24286734
TI  - Abnormal left ventricular rotation and twist in adult patients with corrected
      tetralogy of Fallot.
AB  - AIMS: Left ventricular (LV) dysfunction is a major determinant of late adverse
      clinical outcome in adult patients with tetralogy of Fallot (ToF). Therefore,
      early detection is important. Speckle-tracking echocardiography (STE) has emerged
      as a quantitative technique to assess LV function. The aim of this study was to
      evaluate LV rotation and twist with STE in adult ToF patients and their
      association with right ventricular (RV) and LV dimensions and function, exercise
      capacity, and NT-proBNP level. METHODS: Eighty-two ToF patients and 56 healthy
      controls matched for age and gender underwent echocardiography,
      electrocardiography, cardiac magnetic resonance imaging (CMR), bicycle ergometry,
      and NT-proBNP measurement. For STE, short-axis parasternal views were obtained at
      the LV base and apex. We analysed LV apical and basal rotation curves and
      calculated LV twist. RESULTS: Of the 82 ToF patients (55% male, age 33 +/- 10
      years, 98% NYHA I), 58 (71%) had normal twist, but lower than the controls [12.5
      (IQR: 6.6) vs. 16.9 (IQR: 8.2) degrees, P = 0.002] mainly due to decreased apical
      rotation. Twenty-one (26%) patients had abnormal apical rotation which was
      associated with larger LV dimensions and decreased systolic biventricular
      function. Multivariable regression analyses showed positive relations of LV twist
      with biventricular systolic function measured with echocardiography as well as
      CMR. CONCLUSION: The majority of adults with corrected ToF show a reduced LV
      twist. Strikingly, one-quarter of these patients have an abnormal apical rotation
      which is associated with decreased systolic LV and RV function. These findings
      suggest that abnormal apical rotation is a new objective diagnostic criterion for
      detection of ventricular dysfunction.

PMID- 24286735
TI  - Comprehensive cardiovascular magnetic resonance for monitoring the response to
      therapy in pericardial tuberculosis.

PMID- 24286733
TI  - The German version of the Four Habits Coding Scheme - association between
      physicians' communication and shared decision making skills in the medical
      encounter.
AB  - OBJECTIVE: To translate a measure of physicians' communication skills, the Four
      Habits Coding Scheme (4HCS), into German, to examine its psychometric properties,
      and to analyze its association with the OPTION Scale, which assesses physicians'
      shared decision making (SDM) behavior. METHODS: We performed a secondary data
      analysis of 67 audio-recorded medical consultations. Reliability, internal
      consistency, and factorial validity of the translated 4HCS were analyzed. The
      association with the OPTION Scale was examined using correlation and linear
      regression. RESULTS: Testing of reliability revealed intraclass correlation
      coefficients above .70. Results regarding internal consistency and factorial
      validity were inconclusive. The correlations between the OPTION score and the
      four dimensions of the 4HCS were .04 (p=.782), -.14 (p=.303), -.15 (p=.279) and
      .55 (p<.001), respectively. In multiple regression the four dimensions of the
      4HCS explained substantial amount of variation in the OPTION scores (R(2)=.42,
      P<.001). CONCLUSION: The measure showed good observer reliability, however
      further testing is necessary. Due to the strong interrelation of both measures,
      SDM should be seen in the context of broader communication skills. PRACTICE
      IMPLICATIONS: The 4HCS can be used in research and medical education. Further
      studies are necessary that investigate SDM within the context of communication
      skills.

PMID- 24286736
TI  - Minimally invasive anesthesia in wide awake hand surgery.
AB  - Tumescent minimally invasive local anesthesia is eliminating the need for
      sedation and proximal nerve blocks as well as all of their risks, costs, and
      inconveniences. It has facilitated advances in procedures such as hand fracture
      reduction, tendon repair, and tendon transfer by allowing the surgeon to see
      cooperative patient active movement during the surgery. It has improved the
      patient experience for simple hand operations such as carpal tunnel release.

PMID- 24286737
TI  - Minimally invasive finger fracture management: wide-awake closed reduction, K
      wire fixation, and early protected movement.
AB  - We prefer wide-awake finger fracture reduction, closed percutaneous K-wire
      fixation, and early protected movement to treat phalangeal fractures. This
      approach allows intraoperative visualization of active movement after K-wire
      fixation with the possibility of adjustments during the case. It also negates the
      need for extensive dissection with subsequent scar formation between the tendons
      and the bone. It provides the same advantages that are provided by early
      protected movement after flexor tendon repair.

PMID- 24286738
TI  - Minimally invasive treatment of Raynaud phenomenon: the role of botulinum type A.
AB  - Although the mechanism is unknown, Btx-A injection may be an effective,
      localized, nonsurgical treatment option without addictive properties or systemic
      side effects for the treatment of ischemic digits. Clinical research supports the
      safety and efficacy of injection of Btx-A for the treatment of Raynaud
      phenomenon.

PMID- 24286739
TI  - Collagenase injections for treatment of Dupuytren disease.
AB  - Palmodigital fasciectomy remains the gold standard. The initial outcome is, in my
      experience, far more predictable than either NA or enzyme fasciotomy (EF). It is
      also a more durable treatment. NA and EF can be conceptualized as similar
      procedures--one uses a needle and the other an enzyme to weaken a cord sufficient
      to be able to rupture it and thus straighten a contracted joint. Both are less
      invasive and the hand is quick to recover. Both procedures are equally initially
      effective. CHH seems to offer greater durability. Today's patients are often
      better educated and seek a specific type of treatment, in particular, effective
      nonoperative treatment. Pharmaceutical companies now market directly and
      effectively to patients, and this strategy and Internet use have already resulted
      in an increase in the number of patients searching for practitioners willing to
      administer and capable of administering collagenase treatment.

PMID- 24286740
TI  - Needle aponeurotomy for the treatment of Dupuytren's disease.
AB  - PNA is one of many treatments available for the treatment of hand contractures
      resulting from Dupuytren's disease. It is generally recommended for elderly
      patients with less severe contractures who desire a less invasive procedure, or
      as a first stage to delay surgery in those with more aggressive disease. The
      procedure is safe and easily tolerated by patients, but there is a high rate of
      recurrence.

PMID- 24286741
TI  - Percutaneous release of trigger fingers.
AB  - Open surgery has been indicated as the surgical treatment for trigger finger for
      many years; however, minimally invasive techniques are replacing conventional
      methods. Minimally invasive techniques enable early recovery of the patient with
      minimal damage to soft tissues. The authors' study showed that levels of
      effectiveness of open surgical and percutaneous methods were superior to those of
      the conservative method using corticosteroid based on the cure and reappearance
      rates of the trigger. Percutaneous pulley release for treating trigger finger is
      a safe, effective, and minimally invasive surgical alternative.

PMID- 24286742
TI  - Endoscopic carpal tunnel release.
AB  - ECTR is an elegant minimally invasive operative treatment of CTS, providing a
      rapid rehabilitation without increasing the risk of complications. However, there
      is a significant learning curve and the cost of the operation is significantly
      higher than with conventional open technique. However, the faster rehabilitation
      and the probability of reducing sick leave may lead to ECTR being overall more
      cost-effective than open CTR.

PMID- 24286743
TI  - Endoscopic release of the cubital tunnel.
AB  - It is safe to say that in situ decompression of the ulnar nerve in cubital tunnel
      syndrome has been demonstrated to achieve equivalent functional results when
      compared with more elaborate techniques, such as decompression with nerve
      transposition. The evolution toward procedures associated with less patient
      morbidity is reflected by the introduction of endoscopic techniques for the
      treatment of cubital tunnel syndrome. The authors have incorporated the
      endoscopic approach as proposed by Hoffmann and Siemionow into their practice and
      have obtained favorable results. Although the skin incision can frequently be
      kept to a minimum (<2 cm), superior visualization associated with this approach
      allows for in situ decompression of the ulnar nerve along a distance of up to 30
      cm. Despite the extent of decompression performed, operative morbidity is
      minimal, with return to full duty being the rule even in manual laborers within
      10 to 14 days postoperatively.

PMID- 24286745
TI  - Arthroscopic excision of ganglion cysts.
AB  - Arthroscopy is an advancing field in orthopedics, the applications of which have
      been expanding over time. Traditionally, excision of ganglion cysts has been done
      in an open fashion. However, more recently, studies show outcomes following
      arthroscopic excision to be as good as open excision. Cosmetically, the incisions
      are smaller and heal faster following arthroscopy. In addition, there is the
      suggested benefit that patients will regain function and return to work faster
      following arthroscopic excision. More prospective studies comparing open and
      arthroscopic excision of ganglion cysts need to be done in order to delineate if
      there is a true functional benefit.

PMID- 24286744
TI  - Minimal-incision in situ ulnar nerve decompression at the elbow.
AB  - With initiatives to decrease operative morbidity, complications, and associated
      costs, minimalincision techniques have found an expanding role within multiple
      specialties. Minimal-incision in situ open techniques for ulnar nerve release at
      the elbow provide adequate exposure and reproducible, satisfactory outcomes.
      Furthermore, there is no need for endoscopic equipment and the resultant
      dependence on staff adequately trained to operate and troubleshoot equipment.
      More robust research with a focus on complications and standard outcome measures
      will be required to further define the role of minimal-incision techniques. This
      technical modification, however, augments the increasing armamentarium of the
      hand surgeon.

PMID- 24286746
TI  - Minimally invasive approaches to ulnar-sided wrist disorders.
AB  - Ulnar-sided wrist pain is a common cause of pain and disability, which has long
      been a diagnostic and therapeutic dilemma for hand surgeons. A thorough
      understanding of the anatomy, clinical examination, and radiographic evaluation
      is essential to establish a focused differential diagnosis, with the cause of
      disability often being multifactorial. Arthroscopy is particularly well suited to
      both directly visualize and treat multiple causes of ulnar-sided wrist pain,
      including pathology of the TFCC, UIS, LTIL tears, and hamate arthrosis.

PMID- 24286747
TI  - Use of arthroscopy for the treatment of scaphoid fractures.
AB  - Arthroscopy allows the surgeon to use smaller incisions and still have
      predictable outcomes in the treatment of scaphoid fractures. Similar to large
      joint arthroscopy, the ability to visualize the fracture site allows one to not
      only fine tune the reduction and to assess the vascularity of the fracture
      fragments but to evaluate and treat any associated soft tissue injuries that may
      affect the end result. Specialized equipment and a basic knowledge of wrist
      arthroscopy however are required.

PMID- 24286748
TI  - Minimally invasive hand surgery. Preface.

PMID- 24286750
TI  - Exploring the function of selective attention and hypervigilance for threat in
      anxiety.
AB  - Theoretical frameworks of anxiety propose that attentional biases to threat
      related stimuli cause or maintain anxious states. The current paper draws on
      theoretical frameworks and key empirical studies to outline the distinctive
      attentional processes highlighted as being important in understanding anxiety. We
      develop a conceptual framework to make a distinction between two attentional
      biases: selective attention to threat and hypervigilance for threat. We suggest
      that these biases each have a different purpose and can account for the typical
      patterns of facilitated and impaired attention evident in anxious individuals.
      The framework is novel in its specification of the eye movement behavior
      associated with these attentional biases. We highlight that selective attention
      involves narrowing overt attention onto threat to ensure that these stimuli
      receive processing priority, leading to rapid engagement with task-relevant
      threat and delayed disengagement from task-irrelevant threat. We show that
      hypervigilance operates in the presence and absence of threat and involves
      monitoring for potential dangers via attentional broadening or excessive scanning
      of the environment with numerous eye movements, leading to improved threat
      detection and increased distraction from task-irrelevant threat. We conclude that
      future research could usefully employ eye movement measures to more clearly
      understand the diverse roles of attention in anxiety. 

PMID- 24286749
TI  - Organization of DNA partners and strand exchange mechanisms during Flp site
      specific recombination analyzed by difference topology, single molecule FRET and
      single molecule TPM.
AB  - Flp site-specific recombination between two target sites (FRTs) harboring non
      homology within the strand exchange region does not yield stable recombinant
      products. In negatively supercoiled plasmids containing head-to-tail sites, the
      reaction produces a series of knots with odd-numbered crossings. When the sites
      are in head-to-head orientation, the knot products contain even-numbered
      crossings. Both types of knots retain parental DNA configuration. By carrying out
      Flp recombination after first assembling the topologically well defined Tn3
      resolvase synapse, it is possible to determine whether these knots arise by a
      processive or a dissociative mechanism. The nearly exclusive products from head
      to-head and head-to-tail oriented "non-homologous" FRT partners are a 4-noded
      knot and a 5-noded knot, respectively. The corresponding products from a pair of
      native (homologous) FRT sites are a 3-noded knot and a 4-noded catenane,
      respectively. These results are consistent with non-homology-induced two rounds
      of dissociative recombination by Flp, the first to generate reciprocal
      recombinants containing non-complementary base pairs and the second to produce
      parental molecules with restored base pairing. Single molecule fluorescence
      resonance energy transfer (smFRET) analysis of geometrically restricted FRTs,
      together with single molecule tethered particle motion (smTPM) assays of
      unconstrained FRTs, suggests that the sites are preferentially synapsed in an
      anti-parallel fashion. This selectivity in synapse geometry occurs prior to the
      chemical steps of recombination, signifying early commitment to a productive
      reaction path. The cumulative topological, smFRET and smTPM results have
      implications for the relative orientation of DNA partners and the directionality
      of strand exchange during recombination mediated by tyrosine site-specific
      recombinases. 

PMID- 24286751
TI  - Influence of the pore structure and surface chemical properties of activated
      carbon on the adsorption of mercury from aqueous solutions.
AB  - Reactivation and chemical modification were used to obtain modified activated
      carbons with different pore structure and surface chemical properties. The
      samples were characterized by nitrogen absorption-desorption, Fourier transform
      infrared spectroscopy and the Bothem method. Using mercury chloride as the target
      pollutant, the Hg(2+) adsorption ability of samples was investigated. The results
      show that the Hg(2+) adsorption capacity of samples increased significantly with
      increases in micropores and acidic functional groups and that the adsorption
      process was exothermic. Different models and thermodynamic parameters were
      evaluated to establish the mechanisms. It was concluded that the adsorption
      occurred through a monolayer mechanism by a two-speed process involving both
      rapid adsorption and slow adsorption. The adsorption rate was determined by
      chemical reaction. 

PMID- 24286752
TI  - Microphytobenthic response to mussel farm biodeposition in coastal sediments of
      the northern Adriatic Sea.
AB  - The effects of long-line mussel farming on microphytobenthos were investigated in
      a coastal area of the Gulf of Trieste. Sediment grain-size, organic matter
      content, microalgal abundance and community structure were analysed in September
      2008 and March 2009. Four areas were sampled: a twenty-year farm, a four-year
      farm, a disused farm and a reference site. Principal component analysis (PCA)
      highlighted a decreasing gradient of organic matter content from the twenty-year
      farm to the control. Mussel farming seemed to influence microphytobenthic
      abundance with higher densities in the oldest farm. Three genera were dominant;
      Navicula and Gyrosigma seemed to be stimulated by the organic load under the
      active farms while we infer that Nitzschia proliferation was limited by shade
      caused by mussel ropes. In the PCA, samplings of the disused farm were placed in
      between the still active farms and the control, indicating the partial recovery
      occurred in this site. 

PMID- 24286753
TI  - Chronology of your health events: approaches to extracting temporal relations
      from medical narratives.

PMID- 24286754
TI  - Aquaporin 3 and 8 are down-regulated in TNBS-induced rat colitis.
AB  - Aquaporins (AQPs) plays an important role in transcellular water movement, but
      the AQPs expression profile has not been demonstrated in 2,4,6-trinitrobenzene
      sulfonic acid (TNBS)-induced colitis which closely mimics human Crohn's disease
      (CD) histopathologically. To solve the problem, 30 female Sprague-Dawley (SD)
      rats were randomly divided into a model group (n=18), an ethanol control group
      (n=6) and a normal control group (n=6). On day 1, the rats in the model group
      received TNBS+50% ethanol via the rectum, while the ethanol control rats received
      an equal volume of 50% ethanol and the normal control rats did not receive any
      treatment. All rats were sacrificed on day 7, and ileum, proximal colon and
      distal colon specimens were obtained to examine the alteration in AQP3 and AQP8
      using real-time polymerase chain reaction, Western blot analysis and
      immunohistochemistry. As a result, exposure to TNBS+ethanol resulted in a marked
      decrease in both the mRNA and protein expression of AQP3 and AQP8, with the
      exception of AQP8 protein which was negative in the distal colon in all three
      groups. These reductions in AQP3 and AQP8 were accompanied by an increase in
      intestinal inflammation and injury. The results obtained here implied that both
      AQP3 and AQP8 may be involved in the pathogenesis of inflammatory bowel disease. 

PMID- 24286755
TI  - Processing of glutathionylcobalamin by a bovine B12 trafficking chaperone bCblC
      involved in intracellular B12 metabolism.
AB  - Glutathionylcobalamin (GSCbl) is a biologically relevant vitamin B12 derivative
      and contains glutathione as the upper axial ligand thought formation of a cobalt
      sulfur bond. GSCbl has been shown to be an effective precursor of enzyme
      cofactors, however processing of the cobalamin in intracellular B12 metabolism
      has not been fully elucidated. In this study, we discovered that bCblC, a bovine
      B12 trafficking chaperone, catalyzes elimination of the glutathione ligand from
      GSCbl by using the reduced form of glutathione (GSH). Deglutathionylation
      products are base-off cob(II)alamin and glutathione disulfide, which are
      generated stoichiometrically to GSH. Although cob(I)alamin was not detected due
      to its instability, deglutathionylation is likely analogous to dealkylation of
      alkylcobalamins, which uses the thiolate of GSH for nucleophilic displacement.
      The catalytic turnover number for the deglutathionylation of GSCbl is >=1.62+/
      0.13 min(-1), which is, at least, an order of magnitude higher than that for
      elimination of upper axial ligands from other cobalamins. Considering the
      prevalence of GSH at millimolar concentrations in cells, our results explain the
      previous finding that GSCbl is more effective than other cobalamins for synthesis
      of enzyme cofactors.

PMID- 24286756
TI  - Acute exercise-induced activation of Phox2b-expressing neurons of the
      retrotrapezoid nucleus in rats may involve the hypothalamus.
AB  - The rat retrotrapezoid nucleus (RTN) contains neurons that have a well-defined
      phenotype characterized by the presence of vesicular glutamate transporter 2
      (VGLUT2) mRNA and a paired-like homeobox 2b (Phox2b)-immunoreactive (ir) nucleus
      and the absence of tyrosine hydroxylase (TH). These neurons are important to
      chemoreception. In the present study, we tested the hypothesis that the
      chemically-coded RTN neurons (ccRTN) (Phox2b(+)/TH(-)) are activated during an
      acute episode of running exercise. Since most RTN neurons are excited by the
      activation of perifornical and lateral hypothalamus (PeF/LH), a region that
      regulates breathing during exercise, we also tested the hypothesis that PeF/LH
      projections to RTN neurons contribute to their activation during acute exercise.
      In adult male Wistar rats that underwent an acute episode of treadmill exercise,
      there was a significant increase in c-Fos immunoreactive (c-Fos-ir) in PeF/LH
      neurons and RTN neurons that were Phox2b(+)TH(-) (p<0.05) compared to rats that
      did not exercise. Also the retrograde tracer Fluoro-Gold that was injected into
      RTN was detected in c-Fos-ir PeF/LH (p<0.05). In summary, the ccRTN neurons
      (Phox2b(+)TH(-)) are excited by running exercise. Thus, ccRTN neurons may
      contribute to both the chemical drive to breath and the feed-forward control of
      breathing associated with exercise. 

PMID- 24286757
TI  - Detection and identification of speech sounds using cortical activity patterns.
AB  - We have developed a classifier capable of locating and identifying speech sounds
      using activity from rat auditory cortex with an accuracy equivalent to behavioral
      performance and without the need to specify the onset time of the speech sounds.
      This classifier can identify speech sounds from a large speech set within 40 ms
      of stimulus presentation. To compare the temporal limits of the classifier to
      behavior, we developed a novel task that requires rats to identify individual
      consonant sounds from a stream of distracter consonants. The classifier
      successfully predicted the ability of rats to accurately identify speech sounds
      for syllable presentation rates up to 10 syllables per second (up to 17.9 +/- 1.5
      bits/s), which is comparable to human performance. Our results demonstrate that
      the spatiotemporal patterns generated in primary auditory cortex can be used to
      quickly and accurately identify consonant sounds from a continuous speech stream
      without prior knowledge of the stimulus onset times. Improved understanding of
      the neural mechanisms that support robust speech processing in difficult
      listening conditions could improve the identification and treatment of a variety
      of speech-processing disorders.

PMID- 24286758
TI  - Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus
      transgenic mice.
AB  - BACKGROUND: Several studies have demonstrated that cancer can develop with the
      contribution of bone marrow-derived cancer stem cells. We evaluated the possible
      involvement of bone marrow-derived stem cells in hepatocarcinogenesis in a
      hepatitis B virus (HBV) transgenic mouse model. METHODS: Bone marrow cells from
      wild type male mice were transplanted into sublethally irradiated, female, HBV
      transgenic mice with hepatocarcinoma nodules. Four months later, liver tissue was
      examined to localize neoplastic nodules/foci and characterize cells by evaluating
      the Y-chromosome and the hepatocyte lineage marker hepatocyte nuclear factor-1
      (HNF1), as well as the HBsAg encoding gene (HBs-Eg) and HBsAg protein (HBs-Pr)
      (present only in cells of female origin). RESULTS: Hepatocytes were HBs-Eg/HBs-Pr
      positive in "normal" tissue, while resulted only HBs-Eg-positive in regenerative
      areas. Neoplastic foci/nodules were both HBs-Eg/HBs-Pr-negative. In the liver, 19
      +/- 5% of cells were Y-chromosome-positive and about one fifth were HNF1
      positive. Y-chromosome and HBs-Eg colocalized in HNF1-positive cells. Y
      chromosome-positive cells never localized in neoplastic foci/nodules (HBs-Pr/HBs
      Eg-negative). CONCLUSIONS: Bone marrow-derived stem cells participate in the
      hepatic regenerative process but not in neoplastic growth. Simultaneous detection
      of both Y-chromosome and HBs-Eg in the nucleus of an HNF1-positive cell
      (hepatocyte) demonstrates a phenomenon of cell fusion.

PMID- 24286760
TI  - Autoimmunity, inflammation, and psychosis: a search for peripheral markers.
AB  - Accumulating evidence supports the view that deregulation of the immune system
      represents an important vulnerability factor for psychosis. In a subgroup of
      psychotic patients, the high comorbidity with autoimmune and chronic inflammatory
      conditions suggests a common underlying immune abnormality leading to both
      conditions. The reviewed data of affective and nonaffective psychosis show that
      if immune biomarkers exist for such immune abnormality, they may be found in
      raised macrophage/monocyte inflammatory activation patterns (monocytosis, high
      inflammatory gene expression, raised glucocorticoid receptor beta/glucocorticoid
      receptor alpha ratio, and high levels of proinflammatory and anti-inflammatory
      monocyte/macrophage derived cytokines in serum/plasma), reduced T cell
      numbers/proliferation, and TH1 skewing. This activation of the inflammatory
      response system may be suggestive for microglia activation, as these cells are
      the macrophages of the brain. Indeed, there is some evidence of activation of the
      microglia as detected in positron emission tomography scans and in
      histopathology, and it is assumed that this activation disturbs the development
      and function of neuronal circuits in the brain. Further, animal models of
      psychotic conditions (maternal stress and inflammation paradigms) suggest that
      such monocyte/microglia activation could be seen as the result of a combination
      of genetic predisposition and an immune-mediated two-hit model. Infection but
      also environmental stressors during gestation/early life activate microglia,
      perturbing neuronal development, thereby setting the stage for vulnerability for
      later psychotic disorders. A second hit, such as endocrine changes, stress, or
      infection, could further activate microglia, leading to functional abnormalities
      of the neuronal circuitry in the brain and psychosis. 

PMID- 24286759
TI  - Peripheral biomarkers revisited: integrative profiling of peripheral samples for
      psychiatric research.
AB  - Peripheral samples, such as blood and skin, have been used for decades in
      psychiatric research as surrogates for central nervous system samples. Although
      the validity of the data obtained from peripheral samples has been questioned and
      other state-of-the-art techniques, such as human brain imaging, genomics, and
      induced pluripotent stem cells, seem to reduce the value of peripheral cells,
      accumulating evidence has suggested that revisiting peripheral samples is
      worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that
      establishing an understanding of the common signaling and biological processes in
      the brain and peripheral samples is required for the validity of such models.
      First, we present an overview of the available types of peripheral cells and
      describe their advantages and disadvantages. We then briefly summarize the main
      achievements of omics studies, including epigenome, transcriptome, proteome, and
      metabolome analyses, as well as the main findings of functional cellular assays,
      the results of which imply that alterations in neurotransmission, metabolism, the
      cell cycle, and the immune system may be partially responsible for the
      pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we
      discuss the future utility of peripheral samples for the development of
      biomarkers and tailor-made therapies, such as multimodal assays that are used as
      a battery of disease and trait pathways and that might be potent and
      complimentary tools for use in psychiatric research. 

PMID- 24286761
TI  - Synthesis, molecular modeling and biological evaluation of N-benzylidene-2-((5
      (pyridin-4-yl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide derivatives as potential
      anticancer agents.
AB  - A series of new 1,3,4-oxadiazole derivatives (6a-6x) containing pyridine and
      acylhydrazone moieties were synthesized and developed as potential telomerase
      inhibitors. The bioassay tests demonstrated that compounds 6n, 6o, 6q, 6s and 6t
      exhibited significant broad-spectrum anticancer activity with IC50 range from
      0.76 to 9.59 MUM against the four cancer cell lines (HEPG2, MCF7, SW1116 and
      BGC823). Moreover, all the title compounds were assayed for telomerase inhibition
      using the TRAP-PCR-ELISA assay. Compound 6s showed the highest anticancer
      activity with IC50 of 0.76-1.54 MUM against the tested cancer cell lines and
      exhibited the most potent telomerase inhibitory activity with IC50 of 1.18 +/-
      0.14 MUM. The docking simulation was carried out to investigate a possible
      binding mode of compound 6s into the active site of telomerase (pdb. 3DU6) while
      the QSAR model was built to check the previous work as well as to introduce new
      directions.

PMID- 24286762
TI  - Fragment based discovery of arginine isosteres through REPLACE: towards non-ATP
      competitive CDK inhibitors.
AB  - In order to develop non-ATP competitive CDK2/cyclin A inhibitors, the REPLACE
      strategy has been applied to generate fragment alternatives for the N-terminal
      tetrapeptide of the cyclin binding motif (HAKRRLIF) involved in substrate
      recruitment prior to phosphotransfer. The docking approach used for the
      prediction of small molecule mimics for peptide determinants was validated
      through reproduction of experimental binding modes of known inhibitors and
      provides useful information for evaluating binding to protein-protein interaction
      sites. Further to this, potential arginine isosteres predicted using the
      validated LigandFit docking method were ligated to the truncated C-terminal
      peptide, RLIF using solid phase synthesis and evaluated in a competitive binding
      assay. After testing, identified fragments were shown to represent not only
      appropriate mimics for a critical arginine residue but also to interact
      effectively with a minor hydrophobic pocket present in the binding groove.
      Further evaluation of binding modes was undertaken to optimize the potency of
      these compounds. Through further application of the REPLACE strategy in this
      study, peptide-small molecule hybrid CDK2 inhibitors were identified that are
      more drug-like and suitable for further optimization as anti-tumor therapeutics. 

PMID- 24286763
TI  - Aerially transmitted human fungal pathogens: what can we learn from metagenomics
      and comparative genomics?
AB  - In the last few decades, aerially transmitted human fungal pathogens have been
      increasingly recognized to impact the clinical course of chronic pulmonary
      diseases, such as asthma, cystic fibrosis or chronic obstructive pulmonary
      disease. Thanks to recent development of culture-free high-throughput sequencing
      methods, the metagenomic approaches are now appropriate to detect, identify and
      even quantify prokaryotic or eukaryotic microorganism communities inhabiting
      human respiratory tract and to access the complexity of even low-burden microbe
      communities that are likely to play a role in chronic pulmonary diseases. In this
      review, we explore how metagenomics and comparative genomics studies can
      alleviate fungal culture bottlenecks, improve our knowledge about fungal biology,
      lift the veil on cross-talks between host lung and fungal microbiota, and gain
      insights into the pathogenic impact of these aerially transmitted fungi that
      affect human beings. We reviewed metagenomic studies and comparative genomic
      analyses of carefully chosen microorganisms, and confirmed the usefulness of such
      approaches to better delineate biology and pathogenesis of aerially transmitted
      human fungal pathogens. Efforts to generate and efficiently analyze the enormous
      amount of data produced by such novel approaches have to be pursued, and will
      potentially provide the patients suffering from chronic pulmonary diseases with a
      better management. This manuscript is part of the series of works presented at
      the "V International Workshop: Molecular genetic approaches to the study of human
      pathogenic fungi" (Oaxaca, Mexico, 2012). 

PMID- 24286764
TI  - Genetics of male infertility.
AB  - Genetics play an important role in the evaluation of the infertile male. The
      current limitations of classifying the genetic contribution to male infertility
      and the importance of phenotyping men are discussed, and the core concepts
      necessary to interpret most genetic studies are reviewed. The current genetic
      assays used clinically are discussed in detail. The use and interpretation of the
      cystic fibrosis transmembrane receptor assay are examined in the context of men
      with clinical bilateral absence of the vas deferens, a karyotype and Klinefelter
      syndrome, and Y chromosome microdeletions. The role of hormones and epigenetics
      in evaluating the genetic reproductive potential of men is discussed briefly. A
      summary of what the field might look like in 2034 is presented. 

PMID- 24286765
TI  - The office visit.
AB  - This article summarizes the current office-based evaluation of male infertility
      and offers speculation, based on current research, on the future evolution of
      this encounter. A comprehensive history, physical examination, and semen analysis
      remain paramount to directing the evaluation; however, new advances continue to
      refine diagnostic and treatment algorithms. Interpretation of the routine semen
      analysis as well as adjunctive assessments, including reactive oxygen species,
      DNA fragmentation, and fluorescent in situ hybridization (FISH) are discussed.
      The analysis of genetic and endocrine abnormalities is reviewed. 

PMID- 24286766
TI  - Male endocrine dysfunction.
AB  - Evaluation for endocrine function is a pivotal part of the male infertility
      workup. Endocrine dysfunction may result from endogenous and exogenous sources.
      This article describes the traditional roles that the hypothalamic-pituitary
      gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as
      well as other insults that may contribute to hypospermatogenesis. Recent research
      into the role alternative hormonal axes play in spermatogenesis and promising new
      technologies that may correct inborn or acquired endocrinopathies leading to
      impaired sperm growth and maturation are discussed. 

PMID- 24286767
TI  - Lifestyle, environment, and male reproductive health.
AB  - A large number of environmental and lifestyle factors may negatively affect
      spermatogenesis and male fertility. This article enumerates the current state of
      knowledge regarding those that have been identified, and extrapolates the
      predicted magnitude of these effects over the next 20 years based on current
      societal trends. However, it is likely that additional factors have yet to be
      recognized. Additional research is needed to further define and clarify
      environmental factors that affect male fertility in order to mitigate their
      effects.

PMID- 24286768
TI  - Infectious, inflammatory, and immunologic conditions resulting in male
      infertility.
AB  - This article provides an overview of infectious and inflammatory conditions
      associated with male infertility. These conditions may affect several components
      of the male reproductive tract and therefore have the ability to potentially
      alter sperm function. The effect of these conditions on male fertility is poorly
      understood and often underestimated. 

PMID- 24286769
TI  - Obstructive azoospermia.
AB  - Obstructive azoospermia accounts for 40% of azoospermia and results from
      obstruction of the excurrent ducts (due to many causes) at any location between
      the rete testis and the ejaculatory ducts. The diagnosis of obstructive
      azoospermia (OA) requires a stepwise approach to differentiate it from
      nonobstructive OA and to formulate management options. Localization of the site
      of obstruction relies on history, physical examination, and possibly laboratory,
      genetic, imaging tests, and intraoperative findings. The prospects for patients
      with OA are excellent given recent advances in microsurgical approaches and in
      vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Successful
      outcomes are increasingly likely after microsurgical reconstruction techniques,
      permitting non-IVF pregnancies for many couples. When reconstruction is not an
      option, microsurgical sperm retrieval provides excellent outcomes for patients in
      conjunction with IVF and ICSI. 

PMID- 24286770
TI  - Azoospermia due to spermatogenic failure.
AB  - This article summarizes the current literature regarding azoospermia caused by
      spermatogenic failure. The causes and genetic contributions to spermatogenic
      failure are reviewed. Medical therapies including use of hormonal manipulation,
      whether guided by a specific abnormality or empiric, to induce spermatogenesis
      are discussed. The role of surgical therapy, including a discussion of
      varicocelectomy in men with spermatogenic failure, as well as an in-depth review
      of surgical sperm retrieval with testicular sperm extraction and microdissection
      testicular sperm extraction, is provided. Finally, future directions of treatment
      for men with spermatogenic failure are discussed, namely, stem cell and gene
      therapy. 

PMID- 24286771
TI  - Ejaculatory dysfunction.
AB  - Ejaculatory dysfunction may occur after many different disorders ranging from
      traumatic spinal cord injury to diabetes mellitus. With an understanding of the
      many facets and nuances of the ejaculatory apparatus, both anatomic and
      neurologic, the well-versed clinician can proceed along a safe, efficient, and
      appropriate treatment algorithm to help affected men and their partners achieve
      parenthood. 

PMID- 24286772
TI  - The varicocele.
AB  - Varicoceles are an abnormal dilation of the pampiniform plexus of veins within
      the scrotum. Varicoceles are highly prevalent and can result in a myriad of
      deleterious effects on male reproduction. Numerous therapeutic options are
      available for correcting varicoceles, including surgical varicocelectomy and
      radiographic venous embolization. Varicocele correction is a more cost-effective
      therapeutic modality than both intrauterine insemination (IUI) and in vitro
      fertilization (IVF) for affected couples. In summary, varicoceles contribute
      significantly to male reproductive pathology, and varicocele correction is an
      important option for both clinicians and patients to consider in this era of
      assisted reproductive techniques.

PMID- 24286773
TI  - Male contraception: history and development.
AB  - Although the twentieth century has seen great strides in the development of
      female contraception, not a single new agent has been introduced as an approved
      method for common use for male contraception. Condoms (considered uncomfortable
      by some) and vasectomy (a permanent invasive procedure) are the only options
      provided to men, leaving an undue burden on women to bear contraceptive
      responsibility. Significant developments have, however, been made with regard to
      hormonal and nonhormonal contraception, and minor, reversible, procedural
      contraception. This article reviews the currently available, soon to be
      available, and theoretically possible methods of male contraception. 

PMID- 24286774
TI  - Semen assessment.
AB  - Semen analysis initiates the evaluation of the male partner of an infertile
      couple, and is generally the first test ordered when a couple presents with
      concerns of infertility. This article outlines the steps involved in the initial
      evaluation of the man's fertility potential, the interpretation of the results,
      and the prognostic value of these results. A look into the future of this long
      standing test concludes with some interesting concepts for male infertility
      evaluation. 

PMID- 24286775
TI  - Identification and preparation of sperm for ART.
AB  - State-of-the-art techniques attempt to select sperm with the best functional
      capacity to produce pregnancy and, subsequently, healthy offspring. A variety of
      approaches are now being evaluated. Future approaches may allow for selection of
      sperm based on sperm DNA integrity, degree of aneuploidy, or apoptosis. Other
      approaches involve attempting to improve the in vitro function of sperm with
      exposure to compounds such as pentoxifylline or platelet activating factor. In
      the future, we are likely to see significant improvements in the ability to
      select the best sperm for assisted-reproductive-technology procedures and the use
      of these procedures in routine clinical practice. 

PMID- 24286776
TI  - The role of nutraceuticals in male fertility.
AB  - Nutraceuticals are food products that that can provide medical or health benefits
      by preventing or treating disease processes. The high costs associated with
      assisted reproductive techniques for male infertility have led consumers to find
      less expensive alternatives for potential treatment. Nutraceuticals are widely
      available and have many antioxidant properties. This articles reviews the current
      English literature regarding readily available nutraceuticals and their potential
      effects on male infertility and potential side effects with excess intake. 

PMID- 24286777
TI  - The epidemiology of male infertility.
AB  - The purpose of this review is to integrate understanding of epidemiology and
      infertility. A primer on epidemiologic science and an example disease for which
      the design of epidemiologic investigations is readily apparent are provided. Key
      features of infertility that limit epidemiologic investigation are described and
      a survey of available data on the epidemiology of infertility provided. Finally,
      the work that must be completed to move this area of research forward is
      proposed, and, with this new perspective of "infertility as a disease,"
      improvements envisioned in public health that may be gained through improved
      understanding of the epidemiology of male infertility. 

PMID- 24286778
TI  - Reproductive health care delivery.
AB  - Most patients in the United States with reproductive health disorders are not
      covered by their health insurance for these problems. Health insurance plans
      consider reproductive care as a lifestyle choice not as a disease. If coverage is
      provided it is, most often, directed to female factor infertility and advanced
      reproductive techniques, ignoring male factor reproductive disorders. This
      article reviews the history of reproductive health care delivery and its present
      state, and considers its possible future direction. 

PMID- 24286779
TI  - Current management of male infertility.

PMID- 24286780
TI  - The field of male infertility moves fast!

PMID- 24286781
TI  - In addition to its antiviral and immunomodulatory properties, the zebrafish beta
      defensin 2 (zfBD2) is a potent viral DNA vaccine molecular adjuvant.
AB  - It is well known that beta-defensins are key components of the host innate immune
      response against pathogens and potentially provide a link between innate and
      adaptive immunity. In zebrafish (Danio rerio), a vertebrate model species in
      numerous biomedical fields, three beta-defensin isoforms were recently
      identified. To our knowledge, however, studies describing antimicrobial or
      immunomodulatory properties of any of the zebrafish beta-defensins isoforms are
      absent today. Since it is indubitable that deepening the study of zebrafish beta
      defensins would be of interest in this work we investigated whether or not the
      zebrafish beta-defensin 2 (zfBD2) has the antiviral properties described for
      their vertebrate counterparts. Our in vitro and in vivo studies showed that zfBD2
      has antiviral activity, immunomodulatory properties and, most importantly, is a
      potent viral DNA vaccine molecular adjuvant. In addition, a potential
      relationship between zfBD2 activity and the NF-kappaB signaling pathway is
      suggested. Altogether these results show that the zebrafish could be a suitable
      in vivo animal model to study the roles played by beta-defensin 2 in viral
      diseases, vaccinology and even in clinical dermatology. To note that psoriasis
      can be induced in zebrafish and the over-expression of beta-defensin 2 is
      implicated in the inflammatory response associated with this human skin disorder.

PMID- 24286782
TI  - Framing sexual health research: adopting a broader perspective.

PMID- 24286783
TI  - Kaye Wellings: pioneering figure in sexual health.

PMID- 24286784
TI  - Changes in sexual attitudes and lifestyles in Britain through the life course and
      over time: findings from the National Surveys of Sexual Attitudes and Lifestyles
      (Natsal).
AB  - BACKGROUND: Sexual behaviour and relationships are key components of wellbeing
      and are affected by social norms, attitudes, and health. We present data on
      sexual behaviours and attitudes in Britain (England, Scotland, and Wales) from
      the three National Surveys of Sexual Attitudes and Lifestyles (Natsal). METHODS:
      We used a multistage, clustered, and stratified probability sample design. Within
      each of the 1727 sampled postcode sectors for Natsal-3, 30 or 36 addresses were
      randomly selected and then assigned to interviewers. To oversample individuals
      aged 16-34 years, we randomly allocated addresses to either the core sample (in
      which individuals aged 16-74 years were eligible) or the boost sample (in which
      only individuals aged 16-34 years were eligible). Interviewers visited all
      sampled addresses between Sept 6, 2010, and Aug 31, 2012, and randomly selected
      one eligible individual from each household to be invited to participate.
      Participants completed the survey in their own homes through computer-assisted
      face-to-face interviews and self-interview. We analysed data from this survey,
      weighted to account for unequal selection probabilities and non-response to
      correct for differences in sex, age group, and region according to 2011 Census
      figures. We then compared data from participants aged 16-44 years from Natsal-1
      (1990-91), Natsal-2 (1999-2001), and Natsal-3. FINDINGS: Interviews were
      completed with 15,162 participants (6293 men, 8869 women) from 26,274 eligible
      addresses (57.7%). 82.1% (95% CI 81.0-83.1%) of men and 77.7% (76.7-78.7%) of
      women reported at least one sexual partner of the opposite sex in the past year.
      The proportion generally decreased with age, as did the range of sexual practices
      with partners of the opposite sex, especially in women. The increased sexual
      activity and diversity reported in Natsal-2 in individuals aged 16-44 years when
      compared with Natsal-1 has generally been sustained in Natsal-3, but in men has
      generally not risen further. However, in women, the number of male sexual
      partners over the lifetime (age-adjusted odds ratio 1.18, 95% CI 1.08-1.28),
      proportion reporting ever having had a sexual experience with genital contact
      with another woman (1.69, 1.43-2.00), and proportion reporting at least one
      female sexual partner in the past 5 years (2.00, 1.59-2.51) increased in Natsal-3
      compared with Natsal-2. While reported number of occasions of heterosexual
      intercourse in the past 4 weeks had reduced since Natsal-2, we recorded an
      expansion of heterosexual repertoires--particularly in oral and anal sex--over
      time. Acceptance of same-sex partnerships and intolerance of non-exclusivity in
      marriage increased in men and women in Natsal-3. INTERPRETATION: Sexual
      lifestyles in Britain have changed substantially in the past 60 years, with
      changes in behaviour seeming greater in women than men. The continuation of
      sexual activity into later life--albeit reduced in range and frequency-
      emphasises that attention to sexual health and wellbeing is needed throughout the
      life course. FUNDING: Grants from the UK Medical Research Council and the
      Wellcome Trust, with support from the Economic and Social Research Council and
      the Department of Health.

PMID- 24286785
TI  - Prevalence, risk factors, and uptake of interventions for sexually transmitted
      infections in Britain: findings from the National Surveys of Sexual Attitudes and
      Lifestyles (Natsal).
AB  - BACKGROUND: Population-based estimates of prevalence, risk distribution, and
      intervention uptake inform delivery of control programmes for sexually
      transmitted infections (STIs). We undertook the third National Survey of Sexual
      Attitudes and Lifestyles (Natsal-3) after implementation of national sexual
      health strategies, and describe the epidemiology of four STIs in Britain
      (England, Scotland, and Wales) and the uptake of interventions. METHODS: Between
      Sept 6, 2010 and Aug 31, 2012, we did a probability sample survey of 15,162 women
      and men aged 16-74 years in Britain. Participants were interviewed with computer
      assisted face-to-face and self-completion questionnaires. Urine from a sample of
      participants aged 16-44 years who reported at least one sexual partner over the
      lifetime was tested for the presence of Chlamydia trachomatis, type-specific
      human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe
      age-specific and sex-specific prevalences of infection and intervention uptake,
      in relation to demographic and behavioural factors, and explore changes since
      Natsal-1 (1990-91) and Natsal-2 (1999-2001). FINDINGS: Of 8047 eligible
      participants invited to provide a urine sample, 4828 (60%) agreed. We excluded
      278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia
      prevalence was 1.5% (95% CI 1.1-2.0) in women and 1.1% (0.7-1.6) in men.
      Prevalences in individuals aged 16-24 years were 3.1% (2.2-4.3) in women and 2.3%
      (1.5-3.4) in men. Area-level deprivation and higher numbers of partners,
      especially without use of condoms, were risk factors. However, 60.4% (45.5-73.7)
      of chlamydia in women and 43.3% (25.9-62.5) in men was in individuals who had had
      one partner in the past year. Among sexually active 16-24-year-olds, 54.2% (51.4
      56.9) of women and 34.6% (31.8-37.4) of men reported testing for chlamydia in the
      past year, with testing higher in those with more partners. High-risk HPV was
      detected in 15.9% (14.4-17.5) of women, similar to in Natsal-2. Coverage of HPV
      catch-up vaccination was 61.5% (58.2-64.7). Prevalence of HPV types 16 and 18 in
      women aged 18-20 years was lower in Natsal-3 than Natsal-2 (5.8% [3.9-8.6] vs
      11.3% [6.8-18.2]; age-adjusted odds ratio 0.44 [0.21-0.94]). Gonorrhoea (<0.1%
      prevalence in women and men) and HIV (0.1% prevalence in women and 0.2% in men)
      were uncommon and restricted to participants with recognised high-risk factors.
      Since Natsal-2, substantial increases were noted in attendance at sexual health
      clinics (from 6.7% to 21.4% in women and from 7.7% to 19.6% in men) and HIV
      testing (from 8.7% to 27.6% in women and from 9.2% to 16.9% in men) in the past 5
      years. INTERPRETATION: STIs were distributed heterogeneously, requiring general
      and infection-specific interventions. Increases in testing and attendance at
      sexual health clinics, especially in people at highest risk, are encouraging.
      However, STIs persist both in individuals accessing and those not accessing
      services. Our findings provide empirical evidence to inform future sexual health
      interventions and services. FUNDING: Grants from the UK Medical Research Council
      and the Wellcome Trust, with support from the Economic and Social Research
      Council and the Department of Health.

PMID- 24286786
TI  - The prevalence of unplanned pregnancy and associated factors in Britain: findings
      from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).
AB  - BACKGROUND: Unplanned pregnancy is a key public health indicator. We describe the
      prevalence of unplanned pregnancy, and associated factors, in a general
      population sample in Britain (England, Scotland, and Wales). METHOD: We did a
      probability sample survey, the third National Survey of Sexual Attitudes and
      Lifestyles (Natsal-3), of 15,162 men and women aged 16-74 years in Britain,
      including 5686 women of child-bearing age (16-44 years) who were included in the
      pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the
      planning status of pregnancies with known outcomes in the past year, and report
      the annual population prevalence of unplanned pregnancy, using a validated,
      multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy).
      We set the findings in the context of secular trends in reproductive health
      related events, and patterns across the life course. FINDINGS: 9.7% of women aged
      16-44 years had pregnancies with known outcome in the year before interview, of
      which 16.2% (95% CI 13.1-19.9) scored as unplanned, 29.0% (25.2-33.2) as
      ambivalent, and 54.8% (50.3-59.2) as planned, giving an annual prevalence
      estimate for unplanned pregnancy of 1.5% (1.2-1.9). Pregnancies in women aged 16
      19 years were most commonly unplanned (45.2% [30.8-60.5]). However, most
      unplanned pregnancies were in women aged 20-34 years (62.4% [50.2-73.2]). Factors
      strongly associated with unplanned pregnancy were first sexual intercourse before
      16 years of age (age-adjusted odds ratio 2.85 [95% CI 1.77-4.57], current smoking
      (2.47 [1.46-4.18]), recent use of drugs other than cannabis (3.41 [1.64-7.11]),
      and lower educational attainment. Unplanned pregnancy was also associated with
      lack of sexual competence at first sexual intercourse (1.90 [1.14-3.08]),
      reporting higher frequency of sex (2.11 [1.25-3.57] for five or more times in the
      past 4 weeks), receiving sex education mainly from a non-school-based source
      (1.84 [1.12-3.00]), and current depression (1.96 [1.10-3.47]). INTERPRETATION:
      The increasing intervals between first sexual intercourse, cohabitation, and
      childbearing means that, on average, women in Britain spend about 30 years of
      their life needing to avert an unplanned pregnancy. Our data offer scope for
      primary prevention aimed at reducing the rate of unplanned conceptions, and
      secondary prevention aimed at modification of health behaviours and health
      disorders in unplanned pregnancy that might be harmful for mother and child.
      FUNDING: Grants from the UK Medical Research Council and the Wellcome Trust, with
      support from the Economic and Social Research Council and the Department of
      Health.

PMID- 24286787
TI  - Sexual function in Britain: findings from the third National Survey of Sexual
      Attitudes and Lifestyles (Natsal-3).
AB  - BACKGROUND: Despite its importance to sexual health and wellbeing, sexual
      function is given little attention in sexual health policy. Population-based
      studies are needed to understand sexual function across the life course. METHODS:
      We undertook a probability sample survey (the third National Survey of Sexual
      Attitudes and Lifestyles [Natsal-3]) of 15,162 individuals aged 16-74 years who
      lived in Britain (England, Scotland, and Wales). Interviews were done between
      Sept 6, 2010, and Aug 31, 2012. We assessed the distribution of sexual function
      by use of a novel validated measure (the Natsal-SF), which assessed problems with
      individual sexual response, sexual function in a relationship context, and self
      appraisal of sex life (17 items; 16 items per gender). We assess factors
      associated with low sexual function (defined as the lowest quintile of
      distribution of Natsal-SF scores) and the distribution of components of the
      measure. Participants reporting one or more sexual partner in the past year were
      given a score on the Natsal-SF (11,690 participants). 4122 of these participants
      were not in a relationship for all of the past year and we employed the full
      information maximum likelihood method to handle missing data on four relationship
      items. FINDINGS: We obtained data for 4913 men and 6777 women for the Natsal-SF.
      For men and women, low sexual function was associated with increased age, and,
      after age-adjustment, with depression (adjusted odds ratio 3.70 [95% CI 2.90
      4.72] for men and 4.11 [3.36-5.04] for women) and self-reported poor health
      status (2.63 [1.73-3.98] and 2.41 [1.72-3.39]). Low sexual function was also
      associated with experiencing the end of a relationship (1.52 [1.18-1.95] and 1.77
      [1.44-2.17]), inability to talk easily about sex with a partner (2.36 [1.94-2.88]
      and 2.82 [2.28-3.48]), and not being happy in the relationship (2.89 [2.32-3.61]
      and 4.10 [3.39-4.97]). Associations were also noted with engaging in fewer than
      four sex acts in the past 4 weeks (3.13 [2.58-3.79] and 3.38 [2.80-4.09]), having
      had same sex partners (2.28 [1.56-3.35] and 1.60 [1.16-2.20]), paying for sex (in
      men only; 2.62 [1.46-4.71]), and higher numbers of lifetime sexual partners (in
      women only; 2.12 [1.68-2.67] for ten or more partners). Low sexual function was
      also associated with negative sexual health outcomes such as experience of non
      volitional sex (1.98 [1.14-3.43] and 2.18 [1.79-2.66]) and STI diagnosis (1.50
      [1.06-2.11] and 1.83 [1.35-2.47]). Among individuals reporting sex in the past
      year, problems with sexual response were common (41.6% of men and 51.2% of women
      reported one or more problem) but self-reported distress about sex lives was much
      less common (9.9% and 10.9%). For individuals in a sexual relationship for the
      past year, 23.4% of men and 27.4% of women reported an imbalance in level of
      interest in sex between partners, and 18.0% of men and 17.1% of women said that
      their partner had had sexual difficulties. Most participants who did not have sex
      in the past year were not dissatisfied, distressed, or avoiding sex because of
      sexual difficulties. INTERPRETATION: Wide variability exists in the distribution
      of sexual function scores. Low sexual function is associated with negative sexual
      health outcomes, supporting calls for a greater emphasis on sexual function in
      sexual health policy and interventions. FUNDING: Grants from the UK Medical
      Research Council and the Wellcome Trust, with support from the Economic and
      Social Research Council and the Department of Health.

PMID- 24286788
TI  - Associations between health and sexual lifestyles in Britain: findings from the
      third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).
AB  - BACKGROUND: Physical and mental health could greatly affect sexual activity and
      fulfilment, but the nature of associations at a population level is poorly
      understood. We used data from the third National Survey of Sexual Attitudes and
      Lifestyles (Natsal-3) to explore associations between health and sexual
      lifestyles in Britain (England, Scotland, and Wales). METHODS: Men and women aged
      16-74 years who were resident in households in Britain were interviewed between
      Sept 6, 2010, and Aug 31, 2012. Participants completed the survey in their own
      homes through computer-assisted face-to-face interviews and self-interview. We
      analysed data for self-reported health status, chronic conditions, and sexual
      lifestyles, weighted to account for unequal selection probabilities and non
      response to correct for differences in sex, age group, and region according to
      2011 Census figures. FINDINGS: Interviews were done with 15,162 participants
      (6293 men, 8869 women). The proportion reporting recent sexual activity (one or
      more occasion of vaginal, oral, or anal sex with a partner of the opposite sex,
      or oral or anal sex or genital contact with a partner of the same sex in the past
      4 weeks) decreased with age after the age of 45 years in men and after the age of
      35 years in women, while the proportion in poorer health categories increased
      with age. Recent sexual activity was less common in participants reporting bad or
      very bad health than in those reporting very good health (men: 35.7% [95% CI 28.6
      43.5] vs 74.8% [72.7-76.7]; women: 34.0% [28.6-39.9] vs 67.4% [65.4-69.3]), and
      this association remained after adjusting for age and relationship status (men:
      adjusted odds ratio [AOR] 0.29 [95% CI 0.19-0.44]; women: 0.43 [0.31-0.61]).
      Sexual satisfaction generally decreased with age, and was significantly lower in
      those reporting bad or very bad health than in those reporting very good health
      (men: 45.4% [38.4-52.7] vs 69.5% [67.3-71.6], AOR 0.51 [0.36-0.72]; women: 48.6%
      [42.9-54.3] vs 65.6% [63.6-67.4], AOR 0.69 [0.53-0.91]). In both sexes, reduced
      sexual activity and reduced satisfaction were associated with limiting disability
      and depressive symptoms, and reduced sexual activity was associated with chronic
      airways disease and difficulty walking up the stairs because of a health problem.
      16.6% (95% CI 15.4-17.7) of men and 17.2% (16.3-18.2) of women reported that
      their health had affected their sex life in the past year, increasing to about
      60% in those reporting bad or very bad health. 23.5% (20.3-26.9) of men and 18.4%
      (16.0-20.9) of women who reported that their health affected their sex life
      reported that they had sought clinical help (>80% from general practitioners;
      <10% from specialist services). INTERPRETATION: Poor health is independently
      associated with decreased sexual activity and satisfaction at all ages in
      Britain. Many people in poor health report an effect on their sex life, but few
      seek clinical help. Sexual lifestyle advice should be a component of holistic
      health care for patients with chronic ill health. FUNDING: Grants from the UK
      Medical Research Council and the Wellcome Trust, with support from the Economic
      and Social Research Council and Department of Health.

PMID- 24286789
TI  - Lifetime prevalence, associated factors, and circumstances of non-volitional sex
      in women and men in Britain: findings from the third National Survey of Sexual
      Attitudes and Lifestyles (Natsal-3).
AB  - BACKGROUND: Sexual violence is increasingly recognised as a public health issue.
      Information about prevalence, associated factors, and consequences for health in
      the population of Britain (England, Scotland, and Wales) is scarce. The third
      National Survey of Sexual Health Attitudes and Lifestyles (Natsal-3) is the first
      of the Natsal surveys to include questions about sexual violence and the first
      population-based survey in Britain to explore the issue outside the context of
      crime. METHODS: Between Sept 6, 2010, and Aug 31, 2012, we did a probability
      sample survey of women and men aged 16-74 years living in Britain. We asked
      participants about their experience of sex against their will since age 13 years
      and the circumstances surrounding the most recent occurrence. We explored
      associations between ever experiencing non-volitional sex and a range of
      sociodemographic, health, and behavioural factors. We used logistic regression to
      estimate age-adjusted odds ratios to analyse factors associated with the
      occurrence of completed non-volitional sex in women and men. FINDINGS: We
      interviewed 15,162 people. Completed non-volitional sex was reported by 9.8% (95%
      CI 9.0-10.5) of women and 1.4% (1.1-1.7) of men. Median age (interdecile range)
      at most recent occurrence was 18 years (14-32) for women and 16 years (13-30) for
      men. Completed non-volitional sex varied by family structure and, in women, by
      age, education, and area-level deprivation. It was associated with poor health,
      longstanding illness or disability, and treatment for mental health conditions,
      smoking, and use of non-prescription drugs in the past year in both sexes, and
      with binge drinking in women. Completed non-volitional sex was also associated
      with reporting of first heterosexual intercourse before 16 years of age, same-sex
      experience, more lifetime sexual partners, ever being diagnosed with a sexually
      transmitted infection, and low sexual function in both sexes, and, in women, with
      abortion and pregnancy outcome before 18 years of age. In most cases, the person
      responsible was known to the individual, although the nature of the relationship
      differed by age at most recent occurrence. Participants who were younger at
      interview were more likely to have told someone about the event and to have
      reported it to the police than were older participants. INTERPRETATION: These
      data provide the first population prevalence estimates of non-volitional sex in
      Britain. We showed it to be mainly an experience of young age and strongly
      associated with a range of adverse health outcomes in both women and men.
      FUNDING: Grants from the UK Medical Research Council and the Wellcome Trust, with
      support from the Economic and Social Research Council and the Department of
      Health.

PMID- 24286790
TI  - Induction of innate immunity by Aspergillus fumigatus cell wall polysaccharides
      is enhanced by the composite presentation of chitin and beta-glucan.
AB  - Chitin and beta-glucan are conserved throughout evolution in the fungal cell wall
      and are the most common polysaccharides in fungal species. Together, these two
      polysaccharides form a structural scaffold that is essential for the survival of
      the fungus. In the present study, we demonstrated that Aspergillus fumigatus
      alkali-insoluble cell wall fragments (AIF), composed of chitin linked covalently
      to beta-glucan, induced enhanced immune responses when compared with individual
      cell wall polysaccharides. Intranasal administration of AIF induced eosinophil
      and neutrophil recruitment, chitinase activity, TNF-alpha and TSLP production in
      mice lungs. Selective destruction of chitin or beta-glucan from AIF significantly
      reduced eosinophil and neutrophil recruitment as well as chitinase activity and
      cytokine expression by macrophages, indicating the synergistic effect of the cell
      wall polysaccharides when presented together as a composite PAMP. We also showed
      that these cell wall polysaccharides induced chitin-specific IgM in mouse serum.
      Our in vivo and in vitro data indicate that chitin and beta-glucan play important
      roles in activating innate immunity when presented as composite cell wall PAMPs. 

PMID- 24286791
TI  - Looking forward and back: the value of arthroscopy, shoulder controversies, hip
      advancements, cartilage cutting edge, and arthroscopy techniques.

PMID- 24286792
TI  - Lights, camera, action: how to make arthroscopy a star in value-based health
      care.

PMID- 24286793
TI  - The rotator cuff repair mess.

PMID- 24286794
TI  - Return to sports after arthroscopic anterior stabilization in patients aged
      younger than 25 years.
AB  - PURPOSE: To prospectively evaluate the return-to-sports rates after arthroscopic
      anterior stabilization in patients aged younger than 25 years. METHODS: Fifty
      eight patients underwent arthroscopic capsulolabral repair for isolated anterior
      instability. The mean age at the time of surgery was 19.5 years (range, 12 to 24
      years). At a mean follow-up of 27 months (range, 20 to 32 months), 53 patients
      (42 male and 11 female patients) were assessed with American Shoulder and Elbow
      Surgeons, L'Insalata, and visual analog scale scores, as well as physical
      examination. The rate of return to sports and risk factors for postoperative
      recurrence were evaluated. RESULTS: The overall rate of return to sports at final
      follow-up was 87%. Forty patients returned to a preinjury level of sports
      activity after surgery. Six patients returned to less competitive activities.
      Seven patients who had a subsequent traumatic event resulting in dislocation or
      subluxation did not return to sports activities. Open revision repairs were
      performed in 5 patients with recurrent instability. The American Shoulder and
      Elbow Surgeons and L'Insalata scores improved from 66.9 to 83.2 and from 60.4 to
      79.2, respectively (P < .001). The visual analog scale score improved from 3.1 to
      1 (P < .001). No significant loss of external rotation was noted postoperatively
      (mean, 79 degrees ). Mattress repair was associated with a higher return-to
      sports rate (P < .05). Multiple instability episodes (>5) and the presence of a
      Hill-Sachs lesion were associated with postoperative failure (P < .05).
      CONCLUSIONS: Arthroscopic stabilization is a feasible surgical option in the
      young, athletic population. Mattress labral repair was associated with a higher
      rate of return to sports, whereas patients who had ligamentous laxity, multiple
      instability episodes (>5), and Hill-Sachs lesions had the greatest risk of
      recurrence. These factors should be given consideration in planning the
      appropriate treatment for anterior instability in this age group. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 24286795
TI  - Three-dimensional intercondylar notch volumes in a skeletally immature pediatric
      population: a magnetic resonance imaging-based anatomic comparison of knees with
      torn and intact anterior cruciate ligaments.
AB  - PURPOSE: To determine whether 3-dimensional notch volume, measured with magnetic
      resonance imaging (MRI), differs significantly between knees with torn and intact
      anterior cruciate ligaments (ACLs) after sports injury in a skeletally immature
      pediatric population. METHODS: MRI studies of 50 pediatric patients (age range,
      10 to 17 years) with ACL tears were compared with 50 age- and sex-matched intact
      ACL control patients. All patients had open physes and underwent MRI after a
      sports injury. Notch volume was calculated through manual segmentation of notch
      boundaries seen on axial 1.5-T proton density-weighted images. Two-dimensional
      (2D) measurements (notch width and notch width index) were made on coronal proton
      density-weighted MRI studies. Notch volume was compared between groups by use of
      the Mann-Whitney U test. Pearson correlation coefficients were also calculated
      between indices. RESULTS: Notch volume was significantly lower in knees with ACL
      tears than in control knees (5.5 +/- 1.1 cm(3)v 6.4 +/- 1.5 cm(3), P = .002),
      whereas 2D notch width and notch width index did not differ significantly between
      these groups. Girls had significantly smaller notch volumes than boys (5.4 +/-
      1.2 cm(3)v 6.5 +/- 1.3 cm(3), P < .001). Notch volume was not correlated with age
      but was moderately correlated with 2D notch width (r = 0.485, P < .001).
      CONCLUSIONS: In adolescent patients with sports injuries, the 3-dimensional notch
      volume was significantly smaller in knees with ACL tears than in intact-ACL
      control knees. Notch volume was also significantly smaller in girls than in boys
      and did not vary significantly with age. LEVEL OF EVIDENCE: Level III, case
      control study.

PMID- 24286796
TI  - The shape and the thickness of the anterior cruciate ligament along its length in
      relation to the posterior cruciate ligament: a cadaveric study.
AB  - PURPOSE: The purpose of this study was to evaluate the shape of the native
      anterior cruciate ligament (ACL) along its length in relation to the posterior
      cruciate ligament (PCL) and compare it with the size of the 3 commonly used
      autografts (bone-patellar tendon-bone [BPTB], single-bundle hamstring, and double
      bundle hamstring). METHODS: With the knee in extension, we filled the
      intercondylar notch with paraffin, fixing the cruciate ligaments in their natural
      position, in 8 cadaveric specimens. The ACL-PCL tissue specimen, embedded in
      paraffin, was removed en bloc. Gross sections were prepared in the coronal plane
      and were evaluated histologically. The width, thickness, and cross-sectional area
      of both the ACL and PCL were determined. The dimensions of the semitendinosus
      tendon (ST), gracilis tendon (GT), and BPTB grafts were measured and compared
      with those of the native ACL. RESULTS: The PCL occupies the largest part of the
      intercondylar area, leaving only a small space for the ACL in knee extension. The
      ACL midsubstance has a width of 5 mm, resembling a band shape. Only before its
      tibial insertion does the ACL fan out and take the form of its tibial attachment.
      The BPTB graft has a thickness of 5.8 mm, whereas the ST and GT grafts have a
      thickness of 6.25 mm and 4.5 mm, respectively, and are comparable to the
      midsubstance of the ACL but undersized in the tibial insertion (P = .0016 for
      BPTB graft, P = .002 for ST graft, and P = .0003 for GT graft). A quadruple
      looped ST-GT graft, with a diameter of 8 mm, is oversized in the midsubstance (P
      = .0002) but fits better in the tibial attachment. CONCLUSIONS: The ACL
      midsubstance has a width of 5 mm, resembling a band shape. Before its tibial
      insertion, the ACL fans out like a trumpet, taking the form of its wide tibial
      attachment. CLINICAL RELEVANCE: The dimensions of the native ACL have to be
      considered in graft selection for anatomic ACL reconstruction.

PMID- 24286797
TI  - Cartilage repair in Asia: selected reports on research and clinical trials.

PMID- 24286798
TI  - Cartilage repair: 2013 Asian update.
AB  - Despite financial and regulatory hurdles, Asian scientists and clinicians have
      made important contributions in the area of cartilage repair. Because it is
      impossible to include observations on all the published articles in one review,
      our attempt is to highlight Asian progress in this area during recent years (2005
      to the present), reviewing research development and clinical studies. In the
      former, our discussion of in vitro studies focuses on (1) potential sources of
      stem cells--such as mesenchymal stem cells (MSCs) from marrow, cord blood,
      synovium, and mobilized peripheral blood--which are capable of enhancing
      cartilage repair and (2) the use of growth factors and scaffolds with and without
      cells. Our discussion of animal studies attempts to summarize activities in
      evaluating surgical procedures and determining the route of cell administration,
      as well as studies on matrices and scaffolds. It ranges from the use of small
      animals such as rats and rabbits to larger animals like pigs and dogs. The local
      adherent technique, enhancement of microfracture with poly(l-lactic-co-glycolic
      acid) scaffold, adenovirus-mediated bone morphogenic protein (BMP) genes, and
      MSCs--whether they are magnetically labeled, suspended in hyaluronic acid, or
      immobilized with transforming growth factor-beta (TGF-beta)--have all been able
      to engineer a repair of the osteochondral defect. Although published Asian
      reports of clinical studies on cartilage repair are few, the findings of relevant
      trials are summarized in our discussion of these investigations. There has been a
      long history of use of laboratory-derived MSCs for cartilage repair. Recent
      progress has suggested the potential utility of cord blood and mobilized
      peripheral blood in this area, as well as more injectable bone marrow (BM)
      derived stem cells. Finally, we make a few suggestions on the direction of
      research and development activities and the need for collaborative approaches by
      regulatory agencies.

PMID- 24286799
TI  - Nanoparticle delivery of the bone morphogenetic protein 4 gene to adipose-derived
      stem cells promotes articular cartilage repair in vitro and in vivo.
AB  - PURPOSE: To evaluate the effect of poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles delivering pDC316-BMP4-EGFP plasmid into rabbit adipose-derived
      stem cells (ADSCs) in vitro and chondrogenesis of the bone morphogenetic protein
      4 (BMP-4)--transfected ADSCs seeded onto poly(L-lactic-co-glycolic acid) (PLLGA)
      scaffold in a rabbit model. METHODS: Cell viability and transfection efficiency
      of PLGA nanoparticles were measured by Cell Counting Kit-8 (Dojindo, Kumamoto,
      Japan) and flow cytometry. The BMP-4 and chondrogenesis markers were detected by
      real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Thirty
      rabbits (60 knees) with full-thickness cylinder articular cartilage defects
      (diameter, 4.5 mm; depth, 0.8 mm) on the femoral trochlea were divided into a
      group in which the BMP-4--transfected ADSCs were seeded onto PLLGA scaffold and
      implanted into the defects (group ABNP), a group with untransfected ADSCs seeded
      onto scaffold (group ABP), and a group with a scaffold without cells (group P).
      Outcomes were evaluated by histology, Rudert score, Pineda score, and scanning
      electronic microscopy by 2 blinded observers at weeks 6 and 12 postoperatively.
      Statistical analyses were performed with analysis of variance and the Kruskal
      Wallis test. The statistical significance level was set at P < .05. RESULTS: The
      expression of chondrogenesis-related genes and proteins was significantly
      increased in BMP-4--transfected ADSCs in vitro (P < .05). The cell viability was
      79.86% +/- 5.04% after 24 hours. The transfection efficiency was 25.86% +/- 4.27%
      after 72 hours. Defects in group ABNP showed the best in vivo cartilage
      regeneration. At week 12, the Rudert scores in group ABNP (7.00 +/- 1.75) were
      better than those in group ABP (6.00 +/- 2.00) or group P (5.00 +/- 1.75) (P <
      .05), as were the Pineda scores (2.50 +/- 3.00, 5.00 +/- 2.00, and 6.00 +/- 1.75,
      respectively; P < .001). CONCLUSIONS: BMP-4 plasmid can be successfully delivered
      into ADSCs by PLGA nanoparticles and promoted in vitro chondrogenesis. When
      compared with the control cells, BMP-4--transfected ADSCs seeded onto PLLGA
      scaffold significantly improve in vivo chondrogenesis in a rabbit articular
      defect model. CLINICAL RELEVANCE: PLGA nanoparticles and BMP-4 have potential for
      gene therapy in the treatment of chondral defects of the knee.

PMID- 24286800
TI  - Quantitative magnetic resonance imaging assessment of cartilage status: a
      comparison between young men with and without anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: To assess the cartilage status of the knee joints using magnetic
      resonance imaging at least 2 years after anterior cruciate ligament
      reconstruction (ACLR) in young adult men. METHODS: Thirty young male patients
      with unilateral ACLR and 15 age-matched and body mass index--matched healthy men
      (controls) participated in this study. All participants underwent quantitative
      magnetic resonance imaging scans. Three-dimensional dual-echo steady-state
      sagittal images were segmented using solid model software to calculate the mean
      cartilage thickness, and multi-echo sagittal images were segmented with Siemens
      software (Siemens, Erlangen, Germany) to determine the T2 relaxation time of each
      cartilage plate. RESULTS: There was no statistically significant difference in
      the mean thickness of each cartilage plate between the ACLR and control groups (P
      = .9616 for lateral femoral cartilage, P = .5962 for lateral tibial cartilage, P
      = .9328 for patellar cartilage, P = .9712 for trochlear cartilage, P = .4408 for
      medial femoral cartilage, and P = .1933 for medial tibial cartilage). The ACLR
      group had significantly higher T2 values than the control group in the lateral
      femoral cartilage (P < .001), lateral tibia (P = .0011), trochlea (P = .0028),
      medial femur (P < .001), and medial tibia (P < .001). In addition, the patella
      showed no difference in T2 values between the 2 groups (P = .2152). The medial
      compartment cartilage showed a much higher percentage change in cartilage T2
      values in the ACLR group. CONCLUSIONS: Although no difference in cartilage
      thickness was detected between the ACLR group and the control group, the mean T2
      relaxation time in the ACLR patients was significantly longer than that in
      control subjects. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 24286801
TI  - Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees
      with cartilage defects undergoing high tibial osteotomy: a prospective,
      randomized controlled clinical trial with 2 years' follow-up.
AB  - PURPOSE: To analyze the results of the use of intra-articular cultured autologous
      bone marrow-derived mesenchymal stem cell (MSC) injections in conjunction with
      microfracture and medial opening-wedge high tibial osteotomy (HTO). METHODS:
      Fifty-six knees in 56 patients with unicompartmental osteoarthritic knees and
      genu varum were randomly allocated to the cell-recipient group (n = 28) or
      control group (n = 28). Patients who had a joint line congruity angle of more
      than 2 degrees , malalignment of the knee from femoral causes, a fixed flexion
      deformity, or age older than 55 years were excluded. All patients underwent HTO
      and microfracture. The cell-recipient group received intra-articular injection of
      cultured MSCs with hyaluronic acid 3 weeks after surgery, whereas the control
      group only received hyaluronic acid. The primary outcome measure was the
      International Knee Documentation Committee (IKDC) score at intervals of 6 months,
      1 year, and 2 years postoperatively. Secondary outcome measures were Tegner and
      Lysholm clinical scores and 1-year postoperative Magnetic Resonance Observation
      of Cartilage Repair Tissue (MOCART) scores. RESULTS: The median age of the
      patients was 51 years, with a mean body mass index of 23.85. Both treatment arms
      achieved improvements in Tegner, Lysholm, and IKDC scores. After adjustment for
      age, baseline scores, and time of evaluation, the cell-recipient group showed
      significantly better scores. The effect of treatment showed an added improvement
      of 7.65 (95% confidence interval [CI], 3.04 to 12.26; P = .001) for IKDC scores,
      7.61 (95% CI, 1.44 to 13.79; P = .016) for Lysholm scores, and 0.64 (95% CI, 0.10
      to 1.19; P = .021) for Tegner scores. Magnetic resonance imaging scans performed
      1 year after surgical intervention showed significantly better MOCART scores for
      the cell-recipient group. The age-adjusted mean difference in MOCART score was
      19.6 (95% CI, 10.5 to 28.6; P < .001). CONCLUSIONS: Intra-articular injection of
      cultured MSCs is effective in improving both short-term clinical and MOCART
      outcomes in patients undergoing HTO and microfracture for varus knees with
      cartilage defects. LEVEL OF EVIDENCE: Level II, randomized controlled trial.

PMID- 24286802
TI  - The efficacy of platelet-rich plasma in the treatment of symptomatic knee
      osteoarthritis: a systematic review with quantitative synthesis.
AB  - PURPOSE: The purpose of this systematic review was to synthesize the available
      Level I and Level II literature on platelet-rich plasma (PRP) as a therapeutic
      intervention in the management of symptomatic knee osteoarthritis (OA). METHODS:
      A systematic review of Medline, Embase, Cochrane Central Register of Controlled
      Trials, PubMed, and www.clinicaltrials.gov was performed to identify all
      randomized controlled trials and prospective cohort studies that evaluated the
      clinical efficacy of PRP versus a control injection for knee OA. A random-effects
      model was used to evaluate the therapeutic effect of PRP at 24 weeks by use of
      validated outcome measures (Western Ontario and McMaster Universities Arthritis
      Index, visual analog scale for pain, International Knee Documentation Committee
      Subjective Knee Evaluation Form, and overall patient satisfaction). RESULTS: Six
      Level I and II studies satisfied our inclusion criteria (4 randomized controlled
      trials and 2 prospective nonrandomized studies). A total of 577 patients were
      included, with 264 patients (45.8%) in the treatment group (PRP) and 313 patients
      (54.2%) in the control group (hyaluronic acid [HA] or normal saline solution
      [NS]). The mean age of patients receiving PRP was 56.1 years (51.5% male
      patients) compared with 57.1 years (49.5% male patients) for the group receiving
      HA or NS. Pooled results using the Western Ontario and McMaster Universities
      Arthritis Index scale (4 studies) showed that PRP was significantly better than
      HA or NS injections (mean difference, -18.0 [95% confidence interval, -28.8 to 
      8.3]; P < .001). Similarly, the International Knee Documentation Committee scores
      (3 studies) favored PRP as a treatment modality (mean difference, 7.9 [95%
      confidence interval, 3.7 to 12.1]; P < .001). There was no difference in the
      pooled results for visual analog scale score or overall patient satisfaction.
      Adverse events occurred more frequently in patients treated with PRP than in
      those treated with HA/placebo (8.4% v 3.8%, P = .002). CONCLUSIONS: As compared
      with HA or NS injection, multiple sequential intra-articular PRP injections may
      have beneficial effects in the treatment of adult patients with mild to moderate
      knee OA at approximately 6 months. There appears to be an increased incidence of
      nonspecific adverse events among patients treated with PRP. LEVEL OF EVIDENCE:
      Level II, systematic review of Level I and II studies.

PMID- 24286803
TI  - The incidence of complications after posterior hindfoot endoscopy.
AB  - PURPOSE: The purpose of this systematic review was to determine the incidence of
      complications after posterior hindfoot endoscopy. METHODS: Ovid/Medline and
      Google Scholar were systematically searched for pertinent references to be
      included. In addition, we hand-searched common American and European orthopaedic
      and podiatric surgical journals for relevant articles. Articles considered for
      inclusion were published in peer-reviewed journals, described complications after
      posterior hindfoot endoscopy using a standard 2-portal technique, and involved 25
      or more patients treated. RESULTS: We identified 335 potentially relevant
      publications, of which 5 met our inclusion criteria. A total of 452 ankles (452
      patients) were included in this study. Overall, 17 complications (3.8%) occurred,
      with only 8 (1.8%) requiring additional treatment or operative intervention.
      CONCLUSIONS: The endoscopic approach for the treatment of hindfoot and ankle
      pathology is safe with a low incidence of complications. However, additional
      studies with prospective designs should be undertaken to determine the long-term
      patient outcomes using validated scoring systems. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level III and IV studies.

PMID- 24286804
TI  - Inhibitory control gains from higher-order cognitive strategy training.
AB  - The present study examined the transfer of higher-order cognitive strategy
      training to inhibitory control. Middle school students enrolled in a
      comprehension- and reasoning-focused cognitive strategy training program and
      passive controls participated. The training program taught students a set of
      steps for inferring essential gist or themes from materials. Both before and
      after training or a comparable duration in the case of the passive controls,
      participants completed a semantically cued Go/No-Go task that was designed to
      assess the effects of depth of semantic processing on response inhibition and
      components of event-related potentials (ERP) related to response inhibition.
      Depth of semantic processing was manipulated by varying the level of semantic
      categorization required for response selection and inhibition. The SMART-trained
      group showed inhibitory control gains and changes in fronto-central P3 ERP
      amplitudes on inhibition trials; whereas, the control group did not. The results
      provide evidence of the transfer of higher-order cognitive strategy training to
      inhibitory control and modulation of ERPs associated with semantically cued
      inhibitory control. The findings are discussed in terms of implications for
      cognitive strategy training, models of cognitive abilities, and education. 

PMID- 24286805
TI  - Parametric optimization and design validation based on finite element analysis of
      hybrid socket adapter for transfemoral prosthetic knee.
AB  - BACKGROUND: Finite element analysis has been universally employed for the stress
      and strain analysis in lower extremity prosthetics. The socket adapter was the
      principal subject of interest due to its importance in deciding the knee motion
      range. OBJECTIVES: This article focused on the static and dynamic stress analysis
      of the designed hybrid adapter developed by the authors. A standard mechanical
      design validation approach using von Mises was followed. Four materials were
      considered for the analysis, namely, carbon fiber, oil-filled nylon, Al-6061, and
      mild steel. STUDY DESIGN: The paper analyses the static and dynamic stress on
      designed hybrid adapter which incorporates features of conventional male and
      female socket adapters. The finite element analysis was carried out for possible
      different angles of knee flexion simulating static and dynamic gait situation.
      METHODS: Research was carried out on available design of socket adapter.
      Mechanical design of hybrid adapter was conceptualized and a CAD model was
      generated using Inventor modelling software. Static and dynamic stress analysis
      was carried out on different materials for optimization. RESULTS: The finite
      element analysis was carried out on the software Autodesk Inventor Professional
      Ver. 2011. The peak value of von Mises stress occurred in the neck region of the
      adapter and in the lower face region at rod eye-adapter junction in static and
      dynamic analyses, respectively. CONCLUSIONS: Oil-filled nylon was found to be the
      best material among the four with respect to strength, weight, and cost. CLINICAL
      RELEVANCE: Research investigations on newer materials for development of improved
      prosthesis will immensely benefit the amputees. The study analyze the static and
      dynamic stress on the knee joint adapter to provide better material used for
      hybrid design of adapter.

PMID- 24286806
TI  - Do users want to receive a DEKA Arm and why? Overall findings from the Veterans
      Affairs Study to optimize the DEKA Arm.
AB  - BACKGROUND: The purposes of this article are (1) to report on the overall
      desirability of the DEKA Arm by prototype and by level of prosthesis, (2) to
      report on user-perceived benefits of the DEKA Arm as compared to their current
      prostheses, and (3) to summarize user concerns about taking the device home.
      STUDY DESIGN: Qualitative content analysis of data from a multiple case study
      design. METHODS: This study utilized data from 24 upper-limb amputees fit with a
      Gen 2 DEKA Arm and 13 fit with a Gen 3 DEKA Arm. Surveys were administered after
      fitting the DEKA Arm and at the end of training. Subjects recorded audiotaped
      comments about their experiences. All study sessions were videotaped. RESULTS: In
      all, 79% of Gen 2 and 85% of Gen 3 users indicated that either they wanted to
      receive or might want to receive a DEKA Arm. In total, 95% of Gen 2 and 91% of
      Gen 3 prior prosthesis users reported that they were able to perform new
      activities that they were unable to perform with their own device. CONCLUSIONS: A
      large majority of subjects wanted a DEKA Arm, although desirability varied by
      amputation level. CLINICAL RELEVANCE: The majority of amputees in this study
      expressed a desire to receive the DEKA Arm, a device which provides multiple
      powered degrees of freedom and is operated predominantly by foot controls. The
      majority reported functional advantages of the DEKA Arm over their existing
      prostheses.

PMID- 24286807
TI  - MERS coronavirus: data gaps for laboratory preparedness.
AB  - Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in
      2012, many questions remain on modes of transmission and sources of virus. In
      outbreak situations, especially with emerging organisms causing severe human
      disease, it is important to understand the full spectrum of disease, and shedding
      kinetics in relation to infectivity and the ability to transmit the
      microorganism. Laboratory response capacity during the early stages of an
      outbreak focuses on development of virological and immunological methods for
      patient diagnosis, for contact tracing, and for epidemiological studies into
      sources, modes of transmission, identification of risk groups, and animal
      reservoirs. However, optimal use of this core public health laboratory capacity
      requires a fundamental understanding of kinetics of viral shedding and antibody
      response, of assay validation and of interpretation of test outcomes. We reviewed
      available data from MERS-CoV case reports, and compared this with data on
      kinetics of shedding and immune response from published literature on other human
      coronaviruses (hCoVs). We identify and discuss important data gaps, and biases
      that limit the laboratory preparedness to this novel disease. Public health
      management will benefit from standardised reporting of methods used, details of
      test outcomes by sample type, sampling date, in relation to symptoms and risk
      factors, along with the currently reported demographic, clinical and
      epidemiological findings. 

PMID- 24286808
TI  - Adjuvant chemotherapy improves overall survival after TME surgery in mucinous
      carcinoma of the rectum.
AB  - INTRODUCTION: Mucinous tumours of the rectum are characterised by an abundance of
      extracellular mucin within the tumour complex. They are known to have a poor
      prognosis compared to non-mucinous adenocarcinomas. The effect of adjuvant
      chemotherapy on the survival outcomes of patients with mucinous cancer remains
      unclear. This study evaluated the 5-year overall survival of patients with
      mucinous rectal cancer following optimal TME surgery to determine whether
      adjuvant chemotherapy conferred a survival benefit. METHODS: An analysis of a
      prospectively-maintained database was conducted of patients presenting with
      mucinous rectal cancer between 2000 and 2010. Patients with mucinous tumours were
      identified from final pathology reports of the surgical resection specimens. The
      primary outcome was 5-year overall survival; univariate and multivariate analysis
      was performed using Cox proportional hazards regression models. RESULTS: A total
      of 191 patients were included for analysis with mean age of presentation 64.6
      years (36-88 +/- 11). On the fully adjusted multivariate model, EMVI status (HR
      1.853, 95% CI 1.081-3.175) and not being given adjuvant chemotherapy (HR 2.888,
      95% CI 1.801-4.633) were significant for disease recurrence. The 5-year overall
      survival for patients that had undergone adjuvant chemotherapy was 66.1% compared
      with 35.2% (Mantel Cox log-rank test - p < 0.0001). CONCLUSION: This study
      demonstrates that adjuvant chemotherapy is an independent factor for improvement
      in overall survival in patients with mucinous adenocarcinoma. Therefore, patients
      who have undergone TME surgery for mucinous carcinoma of the rectum should be
      offered adjuvant chemotherapy even in the absence of other high-risk features for
      poor outcomes.

PMID- 24286809
TI  - Radiofrequency ablation of the pancreas: two-week follow-up in a porcine model.
AB  - OBJECTIVE: To determine the impact of radiofrequency ablation (RFA) in pancreas
      after two-week follow-up. BACKGROUND: RFA is a novel treatment strategy in
      patients with unresectable locally advanced pancreatic cancer. The histological
      effect and risk of postoperative complications has not been systematically
      addressed in an in-vivo animal model. METHODS: In a porcine model (n = 6), RFA
      was performed via laparotomy with previously determined optimal settings using a
      bipolar probe with 30 mm active length, at 30 W until a total energy of 15 KJ was
      administered. The probe was inserted in the pancreas at 10 mm distance from
      duodenum and portomesenteric vessels (PMV). RFA nearby duodenum was performed
      under continuous duodenal cooling using 100 ml/min saline of 5  degrees C. During
      two weeks the clinical condition was evaluated daily including blood analyses.
      After two weeks, total pancreatoduodenectomy was performed and the obtained
      tissue histopathologically assessed. RESULTS: No mortality occurred during or
      after RFA. Two animals had a serum amylase increase more than threefold the pre
      intervention value without clinical manifestations. Histopathologic assessment
      showed total ablation within the ablation zone, with loss of normal pancreatic
      acinar cell outlines and necrosis. In one animal, focal necrosis of duodenal
      submucosa was seen and in another animal focal fibrosis in the muscular layer of
      the superior mesenteric vein without clinical manifestations. CONCLUSION: No
      major morbidity and no mortality was seen during a period of two weeks after RFA
      with previously validated RFA settings including duodenal cooling and 10 mm
      distance to PMV. Future clinical studies should confirm safety of RFA using the
      settings established here.

PMID- 24286810
TI  - Preliminary beta spectrum measurements using a magnetic spectrometer.
AB  - We report the performances of a double focusing magnetic beta spectrometer. The
      energy resolution was measured using conversion peaks of Cs-137 and Ba-133 at
      0.73% for 624 keV, and 1.33% for 124 keV. The counting efficiency as a function
      of the energy was estimated using a P-32 source and was used to correct the
      measured spectra of Cs-137. The result was compared with the theoretical spectrum
      and we found a good agreement.

PMID- 24286811
TI  - [Chimeric disorders of sex development ovotesticular].

PMID- 24286812
TI  - [Factors associated with overweight, general obesity and abdominal obesity in the
      Madrid Community's adult population. Study PREDIMERC].

PMID- 24286813
TI  - [Secondary amyloidosis in adult onset Still's disease].

PMID- 24286814
TI  - [Atrial fibrillation in elder hospitalized patients].

PMID- 24286815
TI  - Clinicopathologic characteristics of colorectal cancer with microsatellite
      instability.
AB  - Colorectal cancer (CRC) can be classified according to the level of
      microsatellite instability (MSI) exhibited by the tumor. The aim of this study
      was to determine MSI status in CRC from Tunisia and to identify clinical and
      pathological characteristics of MSI-H tumors. Microsatellite status was
      determined by polymerase chain reaction amplification using standard markers
      (BAT25, BAT26, D2S123, D5S346 and D17S250, the Bethesda panel) in 44 CRC cases.
      Molecular results were correlated with pathological and clinical features. Six
      CRC cases (13.8%) showed high-level instability (MSI-H), 14 cases had low level
      instability (MSI-L), and the remainders were stable (MSS). Immunohistochemical
      analysis showed loss of MSH2 protein in 3 cases among the 6 MSI-H tumors, whereas
      no silencing of MLH1 or MSH6 was found in any case. Significant differences in
      age and family history of cancers were observed between MSI-H and MSS/MSI-L
      groups (p=0.01 and p=0.002). However, statistical analysis showed that there were
      no significant differences between MSI-H and MSS/MSI-L tumors in terms of tumor
      location, lymph node involvement and stage of disease. Regarding histological
      features, MSI-H tumors were more likely to be poorly differentiated (p=0.003), to
      have a medullary pattern (p=0.005), and to harbor increased numbers of
      peritumoral lymphocytes (p=0.001). These findings indicate that careful
      observation of the tumor morphology can assist in the identification of unstable
      colorectal cancers requiring molecular investigations. 

PMID- 24286816
TI  - Optimization of PAMAM-gold nanoparticle conjugation for gene therapy.
AB  - The development of efficient and biocompatible non-viral vectors for gene therapy
      remains a great challenge, and exploiting the properties of both nanoparticle
      carriers and cationic polymers is an attractive approach. In this work, we have
      developed gold nanoparticle (AuNP) polyamidoamine (PAMAM) conjugates for use as
      non-viral transfection agents. AuPAMAM conjugates were prepared by crosslinking
      PAMAM dendrimers to carboxylic-terminated AuNPs via EDC and sulfo-NHS chemistry.
      EDC and sulfo-NHS have been utilized widely and in numerous applications such as
      amino acid coupling; however, their use in the coupling of PAMAM dendrimers to
      AuNPs presents new challenges to form effective and stable constructs for
      delivery that have not yet been examined. Enhanced colloidal stability and DNA
      condensation ability was established by probing two critical synthetic
      parameters: the reaction rate of the PAMAM crosslinking step, and the amine to
      carboxyl ratio. Based on this work, increasing the amine to carboxyl ratio during
      conjugation of PAMAM onto AuNPs yielded the optimal vector with respect to
      colloidal stability and transfection efficiency in vitro. AuPAMAM conjugates
      present attractive candidates for non-viral gene delivery due to their commercial
      availability, ease of fabrication and scale-up, high yield, high transfection
      efficiency and low cytotoxicity.

PMID- 24286817
TI  - Failure to observe renewal following retrieval-induced forgetting.
AB  - Recent studies have pursued the nature of inhibition observed in retrieval
      induced forgetting (RIF) tasks. In a RIF paradigm, participants are trained on
      category-exemplar pairs in Phase 1. Then, some exemplars from select categories
      (Rp+ items) receive further practice in Phase 2. At test, impaired recall for non
      practiced exemplars of the practiced categories (Rp- items) is observed relative
      to exemplars from non-practiced categories (Nrp items). This difference
      constitutes RIF. Prior reports of spontaneous recovery from RIF indicate that RIF
      represents a lapse rather than a loss of memory. Empirical analogs and
      theoretical considerations suggest that RIF should also be reversible through a
      change of context between Phase 2 and testing (i.e., renewal). We conducted two
      experiments using human participants to evaluate the context dependency of RIF.
      In both experiments, Phases 1 and 2 occurred in distinctly different contexts
      with subsequent testing occurring in either the Phase 1 context or the Phase 2
      context. RIF was observed in both experiments. Experiment 1 additionally found
      that the magnitude of RIF was not reduced by testing in the Phase 1 context
      relative to testing in the Phase 2 context. Experiment 2 further tested context
      dependency of RIF by (1) increasing the dissimilarity between the two contexts
      and (2) inserting a retention interval between Phase 2 and test for half of the
      participants in each test context condition. The data again indicated no effect
      of the context manipulation. Thus, no renewal from RIF was observed in either
      experiment; moreover, these null findings were supported by Bayesian analyses.
      These results are compared with analogous inhibitory processes in the animal
      memory literature that typically show both physical and temporal context
      dependency. 

PMID- 24286818
TI  - 'Bodyguard' plants: predator-escape performance influences microhabitat choice by
      nightjars.
AB  - Prey are typically assumed to avoid their predators. However, habitat selection
      patterns of prey might depend upon their ability to use particular landscape
      elements to manage their escape options from predator encounters. During two
      breeding seasons, I studied habitat use and behaviour of red-necked nightjars
      (Caprimulgus ruficollis) foraging under the risk of predation by red foxes
      (Vulpes vulpes) in southwestern Spain. Nightjars exhibited nearly invariable
      foraging site choice and body positioning behaviour based on the architecture of
      vegetation near foraging sites. Nightjars actively chose to sit <50 cm from >120
      cm-tall shrubs or trees while facing away from vegetation cover. Vegetation
      behind nightjars significantly increased their aerial escape opportunities from
      terrestrial attacks during their peak activity period, when nightjars reveal
      visible feather bands during their foraging sallies from the ground and their
      cryptic colouration may not always match the background. Spatial overlap of
      nightjars and foxes along roads suggests that microhabitat selection by these
      birds may in part depend on the chance of escape from predator encounters rather
      than on the probability of encountering predators. I conclude that the interplay
      between high escape efficiency and visibility have probably contributed to the
      evolution of foraging site selection by caprimulgids using bare grounds and
      cattle, horse and camel trails as the natural counterpart of roads.

PMID- 24286819
TI  - Systemic administration and local microinjection into the central nervous system
      of the 5-HT(7) receptor agonist LP-211 modify the sleep-wake cycle in the rat.
AB  - The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied
      in adult rats implanted for chronic sleep recordings. Intraperitoneal
      administration of LP-211 (2.5-10mg/kg) during the light phase of the light-dark
      cycle significantly increased wakefulness (W) and reduced rapid-eye-movement
      sleep (REMS) and the number of REM periods during the 6-h recording period.
      Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus
      coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal
      band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM)
      induced also a decrease of REMS. Additionally, microinjection of the 5-HT7
      receptor ligand into the HDB (2 mM) augmented W. Presently, there is no
      satisfactory explanation for the effect of 5-HT7 receptor activation on W and
      REMS occurrence. Additional studies are required to characterize the
      neurotransmitter systems responsible for the actions of LP-211 on the behavioral
      states.

PMID- 24286820
TI  - An evaluation of an airline cabin safety education program for elementary school
      children.
AB  - The knowledge, attitude, and behavior intentions of elementary school students
      about airline cabin safety before and after they took a specially designed safety
      education course were examined. A safety education program was designed for
      school-age children based on the cabin safety briefings airlines given to their
      passengers, as well as on lessons learned from emergency evacuations. The course
      is presented in three modes: a lecture, a demonstration, and then a film. A two
      step survey was used for this empirical study: an illustrated multiple-choice
      questionnaire before the program, and, upon completion, the same questionnaire to
      assess its effectiveness. Before the program, there were significant differences
      in knowledge and attitude based on school locations and the frequency that
      students had traveled by air. After the course, students showed significant
      improvement in safety knowledge, attitude, and their behavior intention toward
      safety. Demographic factors, such as gender and grade, also affected the
      effectiveness of safety education. The study also showed that having the
      instructor directly interact with students by lecturing is far more effective
      than presenting the information using only video media. A long-term evaluation,
      the effectiveness of the program, using TV or video accessible on the Internet to
      deliver a cabin safety program, and a control group to eliminate potential
      extraneous factors are suggested for future studies. 

PMID- 24286821
TI  - Speciation mediated by centromeres.
AB  - Speciation accompanies reproductive isolation in natural populations through
      hybrid sterility or lethality. However, the molecular bases of hybrid lethality
      are mysterious. In this issue of Developmental Cell, Thomae et al. (2013)
      demonstrate that Drosophila speciation factors HMR and LHR form a centromeric
      complex and that increased dosage causes hybrid lethality. 

PMID- 24286822
TI  - A twoferase for lipid transfer at ER-golgi contact sites.
AB  - Reporting in Cell, Mesmin et al. (2013) show how a single molecule of oxysterol
      binding protein, which has a lipid binding domain that solubilizes both sterol
      and PI4P, might integrate its two specificities to drive the two lipids in
      opposite directions across endoplasmic reticulum-Golgi membrane contact sites. 

PMID- 24286823
TI  - The cytokinin side chain commands shooting.
AB  - Functional distinction between structurally diverse cytokinins as essential plant
      hormones has remained enigmatic for decades. In this issue of Developmental Cell,
      Kiba et al. (2013) provide compelling evidence for the central role of CYP735A1/2
      in synthesizing trans-hydroxylated cytokinins, which specify shoot growth, vital
      for energy and biomass production. 

PMID- 24286824
TI  - c-Met-dependent multipotent labyrinth trophoblast progenitors establish placental
      exchange interface.
AB  - The placenta provides the interface for gas and nutrient exchange between the
      mother and the fetus. Despite its critical function in sustaining pregnancy, the
      stem/progenitor cell hierarchy and molecular mechanisms responsible for the
      development of the placental exchange interface are poorly understood. We
      identified an Epcam(hi) labyrinth trophoblast progenitor (LaTP) in mouse placenta
      that at a clonal level generates all labyrinth trophoblast subtypes,
      syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover,
      we discovered that hepatocyte growth factor/c-Met signaling is required for
      sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met
      also disrupted terminal differentiation and polarization of syncytiotrophoblasts,
      leading to intrauterine fetal growth restriction, fetal liver hypocellularity,
      and demise. Identification of this c-Met-dependent multipotent LaTP provides a
      landmark in the poorly defined placental stem/progenitor cell hierarchy and may
      help us understand pregnancy complications caused by a defective placental
      exchange. 

PMID- 24286825
TI  - Loss of dE2F compromises mitochondrial function.
AB  - E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we
      investigated the mechanism of the resistance of Drosophila dDP mutants to
      irradiation-induced apoptosis. Contrary to the prevailing view, this is not due
      to an inability to induce the apoptotic transcriptional program, because we show
      that this program is induced; rather, this is due to a mitochondrial dysfunction
      of dDP mutants. We attribute this defect to E2F/DP-dependent control of
      expression of mitochondria-associated genes. Genetic attenuation of several of
      these E2F/DP targets mimics the dDP mutant mitochondrial phenotype and protects
      against irradiation-induced apoptosis. Significantly, the role of E2F/DP in the
      regulation of mitochondrial function is conserved between flies and humans. Thus,
      our results uncover a role of E2F/DP in the regulation of mitochondrial function
      and demonstrate that this aspect of E2F regulation is critical for the normal
      induction of apoptosis in response to irradiation. 

PMID- 24286826
TI  - Side-chain modification of cytokinins controls shoot growth in Arabidopsis.
AB  - Cytokinins (CKs), a class of plant hormones, are central regulators of plant
      growth and development. Based on numerous physiological and genetic studies, the
      quantitative regulation of cytokinin levels is the major mechanism regulating
      cytokinin action in diverse developmental processes. Here, we identified a
      different mechanism with which the physiological function of CK is modulated
      through side-chain modification (trans-hydroxylation). The trans-hydroxylation
      that forms trans-zeatin (tZ)-type CK from N(6)-(Delta(2)-isopentenyl)adenine (iP)
      type CK is catalyzed by the cytochrome P450 enzymes CYP735A1 and CYP735A2 in
      Arabidopsis. Deficiency in trans-hydroxylation activity results in dramatic
      retardation of shoot growth without affecting total CK quantity, while
      augmentation of the activity enhances shoot growth. Application of exogenous tZ
      but not iP recovers the wild-type phenotype in the mutants, indicating that trans
      hydroxylation modifies the physiological function of CK. We propose that the
      control of cytokinin function by side-chain modification is crucial for shoot
      growth regulation in plants. 

PMID- 24286828
TI  - Entrapment of chromosomes by condensin rings prevents their breakage during
      cytokinesis.
AB  - Successful segregation of chromosomes during mitosis and meiosis depends on the
      action of the ring-shaped condensin complex, but how condensin ensures the
      complete disjunction of sister chromatids is unknown. We show that the failure to
      segregate chromosome arms, which results from condensin release from chromosomes
      by proteolytic cleavage of its ring structure, leads to a DNA damage checkpoint
      dependent cell-cycle arrest. Checkpoint activation is triggered by the formation
      of chromosome breaks during cytokinesis, which proceeds with normal timing
      despite the presence of lagging chromosome arms. Remarkably, enforcing condensin
      ring reclosure by chemically induced dimerization just before entry into anaphase
      is sufficient to restore chromosome arm segregation. We suggest that topological
      entrapment of chromosome arms by condensin rings ensures their clearance from the
      cleavage plane and thereby avoids their breakage during cytokinesis. 

PMID- 24286827
TI  - Homotypic vacuole fusion in yeast requires organelle acidification and not the V
      ATPase membrane domain.
AB  - Studies of homotypic vacuole-vacuole fusion in the yeast Saccharomyces cerevisiae
      have been instrumental in determining the cellular machinery required for
      eukaryotic membrane fusion and have implicated the vacuolar H(+)-ATPase (V
      ATPase). The V-ATPase is a multisubunit, rotary proton pump whose precise role in
      homotypic fusion is controversial. Models formulated from in vitro studies
      suggest that it is the proteolipid proton-translocating pore of the V-ATPase that
      functions in fusion, with further studies in worms, flies, zebrafish, and mice
      appearing to support this model. We present two in vivo assays and use a mutant V
      ATPase subunit to establish that it is the H(+)-translocation/vacuole
      acidification function, rather than the physical presence of the V-ATPase, that
      promotes homotypic vacuole fusion in yeast. Furthermore, we show that
      acidification of the yeast vacuole in the absence of the V-ATPase rescues vacuole
      fusion defects. Our results clarify the in vivo requirements of acidification for
      membrane fusion. 

PMID- 24286829
TI  - The role of Cdc42 and Gic1 in the regulation of septin filament formation and
      dissociation.
AB  - Septins are guanine nucleotide-binding proteins that polymerize into filamentous
      and higher-order structures. Cdc42 and its effector Gic1 are involved in septin
      recruitment, ring formation and dissociation. The regulatory mechanisms behind
      these processes are not well understood. Here, we have used electron microscopy
      and cryo electron tomography to elucidate the structural basis of the Gic1-septin
      and Gic1-Cdc42-septin interaction. We show that Gic1 acts as a scaffolding
      protein for septin filaments forming long and flexible filament cables. Cdc42 in
      its GTP-form binds to Gic1, which ultimately leads to the dissociation of Gic1
      from the filament cables. Surprisingly, Cdc42-GDP is not inactive, but in the
      absence of Gic1 directly interacts with septin filaments resulting in their
      disassembly. We suggest that this unanticipated dual function of Cdc42 is crucial
      for the cell cycle. Based on our results we propose a novel regulatory mechanism
      for septin filament formation and dissociation. DOI:
      http://dx.doi.org/10.7554/eLife.01085.001. 

PMID- 24286830
TI  - Prostate sparing cystectomy for bladder cancer: 20-year single center experience.
AB  - PURPOSE: We evaluated long-term oncologic and functional results after prostate
      sparing cystectomy for bladder cancer. MATERIALS AND METHODS: A total of 120
      patients with cT1-4N0-3 bladder cancer were treated with prostate sparing
      cystectomy between 1994 and 2013, of whom 110 had a followup of 2 years or
      greater and were eligible for analysis. To rule out tumor in the bladder neck,
      prostatic urethra or prostate cancer all patients underwent preoperative
      transurethral biopsy of the bladder neck and prostatic urethra, prostate specific
      antigen measurement and transrectal ultrasound with biopsies. We assessed
      oncologic outcomes (disease specific and recurrence-free survival), recurrence
      rates, prostate cancer and functional results (continence, voiding, and erectile
      and ejaculatory function). RESULTS: Mean patient +/- SD age was 56.2 +/- 8.3
      years and median followup was 77.0 months (IQR 57-116). Two and 5-year disease
      specific survival rates were 76.2% and 66.5%, 2 and 5-year recurrence-free
      survival rates were 71.2% and 66.6%, and distant and local recurrence rates were
      34.2% and 10.0%, respectively. One local recurrence was in the remnant prostatic
      urothelium. Prostate cancer was diagnosed in 2.7% of cases. Complete daytime and
      nighttime continence was achieved in 96.2% and 81.9% of patients, and erectile
      function and antegrade ejaculation were intact in 89.7% and 35.5%, respectively.
      CONCLUSIONS: Our long-term data show that prostate sparing cystectomy is an
      oncologically safe procedure with excellent functional results in a subset of
      carefully selected patients with bladder cancer without evidence of urothelial
      carcinoma in the prostatic urethra/bladder neck and no prostate cancer.

PMID- 24286832
TI  - Permanent draft genome of Rhodopirellula sallentina SM41.
AB  - The genome of Rhodopirellula sallentina SM41 was sequenced as a permanent draft
      to supplement the full genome sequence of the type strain Rhodopirellula baltica
      SH1(T). This isolate is part of a larger study to gain insights into the
      biogeography of Rhodopirellula species in European marine waters, as well as to
      amend the genus description of R. baltica. This genomics resource article is the
      third of a series of five publications reporting in total eight new permanent
      daft genomes of Rhodopirellula species. 

PMID- 24286831
TI  - Permanent draft genomes of the three Rhodopirellula baltica strains SH28, SWK14
      and WH47.
AB  - The genomes of three Rhodopirellula baltica strains were sequenced as permanent
      drafts to complement the full genome sequence of the type strain R. baltica
      SH1(T). The isolates are part of a larger study to infer the biogeography of
      Rhodopirellula species in European marine waters, as well as to amend the genus
      description of R. baltica. This genomics resource article is the first of a
      series of five publications reporting in total eight new permanent daft genomes
      of Rhodopirellula species. 

PMID- 24286833
TI  - Permanent draft genomes of the Rhodopirellula maiorica strain SM1.
AB  - The genome of Rhodopirellula maiorica strain SM1 was sequenced as a permanent
      draft to complement the full genome sequence of the type strain Rhodopirellula
      baltica SH1(T). This isolate is part of a larger study to infer the biogeography
      of Rhodopirellula species in European marine waters, as well as to amend the
      genus description of R. baltica. This genomics resource article is the fifth of a
      series of five publications reporting in total eight new permanent daft genomes
      of Rhodopirellula species. 

PMID- 24286834
TI  - Permanent draft genomes of the two Rhodopirellula europaea strains 6C and SH398.
AB  - The genomes of two Rhodopirellula europaea strains were sequenced as permanent
      drafts to study the genomic diversity within this genus, especially in comparison
      with the closed genome of the type strain Rhodopirellula baltica SH1(T). The
      isolates are part of a larger study to infer the biogeography of Rhodopirellula
      species in European marine waters, as well as to amend the genus description of
      R. baltica. This genomics resource article is the second of a series of five
      publications describing a total of eight new permanent daft genomes of
      Rhodopirellula species. 

PMID- 24286836
TI  - System factors to explain 2009 pandemic H1N1 state vaccination rates for children
      and high-risk adults in US emergency response to pandemic.
AB  - INTRODUCTION: During the 2009-2010 H1N1 pandemic, children and high-risk adults
      had priority for vaccination. Vaccine in short supply was allocated to states pro
      rata by population, but vaccination rates as of January 2010 varied among states
      from 21.3% to 84.7% for children and 10.4% to 47.2% for high-risk adults. States
      had different campaign processes and decisions. OBJECTIVE: To determine program
      and system factors associated with higher state pandemic vaccination coverage for
      children and high-risk adults during an emergency response with short supply of
      vaccine. METHODS: Regression analysis of factors predicting state-specific H1N1
      vaccination coverage in children and high-risk adults, including state campaign
      information, demographics, preventive or health-seeking behavior, preparedness
      funding, providers, state characteristics, and surveillance data. RESULTS: Our
      modeling explained variation in state-specific vaccination coverage with an
      adjusted R-squared of 0.82 for children and 0.78 for high-risk adults. We found
      that coverage of children was positively associated with programs focusing on
      school clinics and with a larger proportion of doses administered in public
      sites; negatively with the proportion of children in the population, and the
      proportion not visiting a doctor because of cost. The coverage for high-risk
      adults was positively associated with shipments of vaccine to "general access"
      locations, including pharmacy and retail, with the percentage of women with a Pap
      smear within the past 3 years and with past seasonal influenza vaccination. It
      was negatively associated with the expansion of vaccination to the general public
      by December 4, 2009. For children and high-risk adults, coverage was positively
      associated with the maximum number of ship-to-sites and negatively associated
      with the proportion of medically underserved population. CONCLUSION: Findings
      suggest that distribution and system decisions such as vaccination venues and
      providers targeted can positively impact vaccination rates for children and high
      risk adults. Additionally, existing health infrastructure, health-seeking
      behaviors, and access affected coverage.

PMID- 24286837
TI  - Posterior corneal astigmatism.

PMID- 24286835
TI  - Epithelial stem cells as mucosal antigen-delivering cells: A novel AIDS vaccine
      approach.
AB  - A key obstacle limiting development of an effective AIDS vaccine is the inability
      to deliver antigen for a sufficient period of time resulting in weak and
      transient protection. HIV transmission occurs predominantly across mucosal
      surfaces; therefore, an ideal vaccine strategy would be to target HIV at mucosal
      entry sites to prevent infection. Such a novel strategy relies on the activation
      of mucosal immune response via presentation of viral antigens by the mucosal
      epithelial cells. The use of a terminally differentiated epithelial cell promoter
      to drive expression of antigens leading to viral protein production in the upper
      layers of the epithelium is central to the success of this approach. Our results
      show that when administered intradermally to mice, a GFP-reporter gene under the
      transcriptional control of the involucrin promoter is expressed in the upper
      layers of the epidermis and, although transduced cells were very low in number,
      high and sustained anti-GFP antibody production is observed in vivo. A subsequent
      experiment investigates the effectiveness of GFP-tagged replication-competent
      SIVdeltaNef and GFP-tagged replication-deficient SIVdeltaVifdeltaNef constructs
      under the transcriptional control of the involucrin promoter. Optimal conditions
      for production of pseudotyped VSV-G viral particles destined to transduce basal
      epithelial stem cells at the mucosal sites of entry of SIV in our animal model
      were determined. Altogether, the data demonstrate the feasibility of an
      epithelium-based vaccine containing involucrin-driven viral antigen encoding
      sequences that integrate into epithelial stem cells and show long-term expression
      in the upper layer of the epithelium even after multiple cycle of epithelia
      renewal. Such epithelium-based vaccine should elicit a long-term immunity against
      HIV/SIV infection at the site of entry of the virus. 

PMID- 24286838
TI  - Suture refixation and recentration of a subluxated capsular tension ring-capsular
      bag-intraocular lens complex.
AB  - We describe a 3-point ab externo technique to refixate and recenter a subluxated
      Cionni capsular tension ring (CTR)-intraocular lens (IOL)-capsular bag complex to
      the sclera. A 9-0 polypropylene suture on a curved needle is looped through the
      eyelet of the CTR and back through a Hoffman scleral tunnel. Two other sutures
      passed in a similar fashion through the fibrotic continuous curvilinear
      capsulorhexis (CCC) edge are used to complete a tripod fixation, which centers
      and stabilizes the IOL. This surgical approach avoids the surgical trauma of
      removing and replacing a subluxated CTR-IOL-capsular bag complex, retains the
      optimal anatomical position, and ensures centration of the IOL.

PMID- 24286839
TI  - Correlation of nuclear density using the Lens Opacity Classification System III
      versus Scheimpflug imaging with phacoemulsification parameters.
AB  - PURPOSE: To grade nuclear cataracts using the Lens Opacity Classification System
      III (LOCS III) and the correlation with maximum nuclear density on Scheimpflug
      imaging and phacoemulsification parameters. SETTING: Tertiary care center.
      DESIGN: Longitudinal interventional study. METHODS: The nuclear density of
      significant age-related cataracts was evaluated by comparing slitlamp images with
      standard photographic charts of the LOCS III system. Maximum nuclear density was
      calculated using a Scheimpflug imaging system (Pentacam). All patients had
      phacoemulsification and posterior chamber intraocular lens implantation.
      Intraoperatively, parameters (eg, phaco time, power consumed, balanced salt
      solution used) were noted and compared with different grades of cataract and
      maximum nuclear densities. RESULTS: One hundred patients with visually
      significant age-related cataract were evaluated. There was a positive linear
      correlation between the LOCS III grading and Scheimpflug maximum nuclear density
      (P<.001). The LOCS III grading and Scheimpflug maximum nuclear density had a
      linear correlation with preoperative corrected distance visual acuity (r = 0.588
      and r = 0.525, respectively), cumulative dissipated energy (CDE) (r = 0.607 and r
      = 0.847, respectively), total ultrasound (US) time (r = 0.627 and r = 0.802,
      respectively), and fluid used (r = 0.623 and r = 0.678, respectively).
      CONCLUSION: Both systems had a linear correlation with total US power, CDE, and
      fluid used; however, the Scheimpflug imaging system had a stronger correlation
      with these phacoemulsification parameters.

PMID- 24286840
TI  - Endothelial keratoplasty for bullous keratopathy in eyes with an anterior chamber
      intraocular lens.
AB  - PURPOSE: To describe how to approach eyes with phakic or pseudophakic bullous
      keratopathy that have an anterior chamber intraocular lens (AC IOL) using thin
      Descemet-stripping endothelial keratoplasty (thin-DSEK) or Descemet membrane
      endothelial keratoplasty (DMEK) with or without AC IOL removal. SETTING: Tertiary
      referral center. DESIGN: Comparative case series. METHODS: Descemet membrane
      endothelial keratoplasty or thin-DSEK was performed in pseudophakic eyes with
      iris-claw AC IOLs (Group 1) or in phakic eyes with angle-supported AC IOLs (Group
      2). In both groups, DMEK was routinely performed except in eyes with insufficient
      corneal transparency or a high risk for graft detachment. Preoperative surgical
      considerations, postoperative corrected distance visual acuity (CDVA),
      endothelial cell density, and complications were documented. RESULTS: In Group 1,
      all AC IOLs were left in situ. In Group 2, AC IOLs were removed in 90% of cases.
      At 6 months, the CDVA was 20/40 (>=0.5 decimal) or better in 36% of eyes in Group
      1 and 90% in Group 2. Graft detachment occurred in 20% of eyes and de novo or
      glaucoma exacerbation in 29%. CONCLUSIONS: Bullous keratopathy treatment in eyes
      with an AC IOL was feasible with DMEK. Intraocular lens removal may be required
      if postoperative complications are anticipated, but not to facilitate surgery.
      Overall, the surgical approach may aim to minimize postoperative complications;
      that is, thin-DSEK in eyes with low visual potential and/or concomitant pathology
      and DMEK in eyes with a phakic AC IOL and normal visual potential.

PMID- 24286841
TI  - Management of the subluxated crystalline lens.
AB  - The surgical management of ectopia lentis presents the ophthalmic surgeon with
      numerous challenges and options. From the clinical evaluation to the surgical
      approach, ectopia lentis patients require additional methodologies, techniques,
      and devices to ensure the best possible outcome. The continued refinement of
      surgical techniques and adjunctive prosthetic devices has led to incremental
      improvements in the ability to achieve successful in-the-bag placement and
      centration of intraocular lenses while reducing complications. A thorough
      understanding of the challenges inherent in ectopia lentis cases and the
      management of intraoperative complications will ensure that surgeons approaching
      the correction of these eyes will achieve the best possible surgical results.

PMID- 24286842
TI  - Refractive surgical problem. December consultation #1.

PMID- 24286843
TI  - December consultation #3.

PMID- 24286844
TI  - December consultation #2.

PMID- 24286845
TI  - December consultation #5.

PMID- 24286846
TI  - December consultation #4.

PMID- 24286847
TI  - December consultation #6.

PMID- 24286848
TI  - December consultation #7.

PMID- 24286849
TI  - December consultation #8.

PMID- 24286850
TI  - Combined transepithelial phototherapeutic keratectomy and corneal collagen
      crosslinking for ectatic disorders: cretan protocol.

PMID- 24286851
TI  - Additional basics for mesopic contrast sensitivity testing and need for use of
      artificial pupil.

PMID- 24286852
TI  - Bridging hypoxia, inflammation and estrogen receptors in thyroid cancer
      progression.
AB  - Thyroid cancer is a common endocrine-related cancer with a higher incidence in
      women than in men. Thyroid tumors are classified on the basis of their
      histopathology as papillary, follicular, medullary, and undifferentiated or
      anaplastic. Epidemiological and in vitro or in vivo studies have suggested a
      correlation between incidence of thyroid malignancies and hormones. In
      particular, growing evidence indicates a role of estrogens and estrogen receptors
      (ERs) in thyroid tumorigenesis, reprogramming and progression. In this scenario,
      estrogens are hypothesized to contribute to the observed female predominance of
      thyroid cancer in reproductive years. However, the precise contribution of
      estrogens in thyroid proliferative disease initiation and progression is not well
      understood. HIF-1alpha and NF-kappaB are two transcription factors very
      frequently activated in tumors and involved in tumor growth, progression and
      resistance to chemotherapy. In fact, HIF-1alpha and NF-kappaB together regulate
      transcription of over a thousand genes that, in turn, control vital cellular
      processes such as adaptation to the hypoxia, metabolic and differentiation
      reprogramming, inflammatory-reparative response, extracellular matrix digestion,
      migration and invasion, adhesion, etc. Because of this wide involvement, they
      could control in an integrated manner the origin of the malignant phenotype.
      Interestingly, hypoxia and inflammation have been sequentially bridged in tumors
      by the discovery that alarmin receptors genes such as RAGE, P2X7 and some TLRs
      are activated by HIF-1alpha; and that, in turn, alarmin receptors strongly
      activate NF-kappaB and proinflammatory gene expression, evidencing all the
      hallmarks of the malignant phenotype. Recently, a large number of drugs have been
      identified that inhibit one or both transcription factors with promising results
      in terms of controlling tumor progression. In addition, many of these inhibitors
      are natural compounds or off-label drugs already used to cure other pathologies.
      Some of them are undergoing clinical trials and soon they will be used alone or
      in combination with standard anti-tumoral agents to achieve a better treatment of
      tumors to achieve a reduction of metastasis formation and, more importantly, a
      net increase in survival. This review highlights the central role of HIF-1alpha
      activated in hypoxic regions of the tumor, of NF-kappaB activation and
      proinflammatory gene expression in transformed thyroid cells to understand their
      progression toward malignancy. The role of ER-alpha will be underlined,
      considering also its role in reprogramming cancer cells. 

PMID- 24286853
TI  - In-vitro activity of polyhexanide alone and in combination with antibiotics
      against Staphylococcus aureus.
AB  - BACKGROUND: The resistance of Staphylococcus aureus is increasing, not only to
      antibiotics but also to antiseptics. AIM: To investigate the activity of the
      antiseptic polyhexanide and several antibiotics against clinical isolates of
      meticillin-susceptible and meticillin-resistant Staphylococcus aureus (MSSA and
      MRSA, respectively). Polyhexanide was tested alone and in combination with
      oxacillin, penicillin G, ampicillin, cefazolin, cefuroxime, imipenem, gentamicin,
      erythromycin, doxycycline, levoflocaxin, linezolid and vancomycin. METHODS: Fifty
      MSSA and 50 MRSA strains, including one vancomycin-intermediate (VISA) strain,
      were tested. All strains were typed by pulsed-field gel electrophoresis (PFGE) to
      exclude testing of clonal isolates. Minimum inhibitory concentrations (MICs) and
      minimum bactericidal concentrations (MBCs) were determined using the serial broth
      microdilution technique according to DIN 58940. Combinations of polyhexanide and
      different antibiotics were investigated using the checkerboard technique.
      FINDINGS: Polyhexanide MICs and MBCs in the range of 0.5-2mg/L were found for
      both MSSA and MRSA, and the VISA strain had MIC and MBC values of 2mg/L. All
      isolates were regarded as susceptible to polyhexanide, and no antagonism was
      observed between polyhexanide and the tested antibiotics. Synergism between
      polyhexanide and some bacteriostatic antibiotics (erythromycin, doxycycline and
      linezolid) was found for some strains. CONCLUSIONS: Polyhexanide appears to be
      suitable for the topical treatment of S. aureus alone and in combination with
      antibiotics.

PMID- 24286854
TI  - Interventions to control nosocomial infections: study designs and statistical
      issues.
AB  - There is a wide range of potential study designs for intervention studies to
      decrease nosocomial infections in hospitals. The analysis is complex due to
      competing events, clustering, multiple timescales and time-dependent period and
      intervention variables. This review considers the popular pre-post quasi
      experimental design and compares it with randomized designs. Randomization can be
      done in several ways: randomization of the cluster [intensive care unit (ICU) or
      hospital] in a parallel design; randomization of the sequence in a cross-over
      design; and randomization of the time of intervention in a stepped-wedge design.
      We introduce each design in the context of nosocomial infections and discuss the
      designs with respect to the following key points: bias, control for non
      intervention factors, and generalizability. Statistical issues are discussed. A
      pre-post-intervention design is often the only choice that will be informative
      for a retrospective analysis of an outbreak setting. It can be seen as a pilot
      study with further, more rigorous designs needed to establish causality. To yield
      internally valid results, randomization is needed. Generally, the first choice in
      terms of the internal validity should be a parallel cluster randomized trial.
      However, generalizability might be stronger in a stepped-wedge design because a
      wider range of ICU clinicians may be convinced to participate, especially if
      there are pilot studies with promising results. For analysis, the use of extended
      competing risk models is recommended. 

PMID- 24286855
TI  - Relation of risk factors with response to carvedilol in heart failure with
      preserved ejection fraction - a report from the Japanese Diastolic Heart Failure
      Study (J-DHF).
AB  - BACKGROUND: The Japanese Diastolic Heart Failure Study (J-DHF) has suggested
      beneficial effects of the standard-dose prescription of carvedilol in heart
      failure with preserved ejection fraction (HFPEF). However, it is unclear whether
      any risk factors modulate the effects of the standard-dose carvedilol. METHODS
      AND RESULTS: Data from 245 patients with HFPEF in J-DHF were evaluated. Decreased
      body mass index, diabetes mellitus, and left atrial (LA) dilatation were
      independent risk factors for both of the primary outcomes (cardiovascular death
      and unplanned hospitalization for heart failure) and another major composite
      outcome (cardiovascular death and unplanned hospitalization for any
      cardiovascular causes) in multivariable analysis. In patients with LA
      diameter>=the median value (43.2mm), standard-dose carvedilol was associated with
      unadjusted hazard ratio (HR) 0.263 [95% confidence interval (CI): 0.080-0.859]
      and covariate adjusted 0.264 (0.080-0.876) for the primary outcome. In those with
      LA diameter<43.2mm, unadjusted and adjusted HRs were 1.123 (0.501-2.514) and
      1.067 (0.472-2.412). A p-value for interaction was 0.046 (unadjusted) and 0.058
      (adjusted). The similar effects of LA diameter were observed regarding another
      major composite outcome. The other risk factors in univariate or multivariable
      analyses did not influence the response to the standard-dose carvedilol.
      CONCLUSIONS: The standard-dose carvedilol may exert greater reduction of the
      incidence of clinical outcomes in the patients with HFPEF and advanced rather
      than mild diastolic dysfunction.

PMID- 24286857
TI  - Burst-suppression with identical bursts: a distinct EEG pattern with poor outcome
      in postanoxic coma.
AB  - OBJECTIVE: To assess the incidence, quantified EEG characteristics, and
      prognostic significance of "burst-suppression with identical bursts" and to
      discuss potential pathophysiological mechanisms. METHODS: Burst-suppression EEGs
      were identified from a cohort of 101 comatose patients after cardiac arrest, and
      from our complete database of 9600 EEGs, since 2005. Patterns with and without
      identical bursts were classified visually by two observers. Of patients after
      cardiac arrest, outcomes were assessed at three and six months. Identical and non
      identical burst-suppression patterns were compared for quantified EEG
      characteristics and clinical outcome. Cross correlation of burstshape was applied
      to the first 500 ms of each burst. RESULTS: Of 9701 EEGs, 240 showed burst
      suppression, 22 with identical bursts. Identical bursts were observed in twenty
      (20%) of 101 comatose patients after cardiac arrest between a median of 12 and 36
      h after the arrest, but not in the six patients with other pathology than
      cerebral ischemia, or the 183 with anesthesia induced burst suppression. Inter
      observer agreement was 0.8 and disagreement always resulted from sampling error.
      Burst-suppression with identical bursts was always bilateral synchronous,
      amplitudes were higher (128 vs. 25 MUV, p=0.0001) and correlation coefficients of
      burstshapes were higher (95% >0.75 vs. 0% >0.75, p<0.0001) than in burst
      suppression without identical bursts. All twenty patients with identical bursts
      after cardiac arrest had a poor outcome versus 10 (36%) without identical bursts.
      CONCLUSION: "Burst-suppression with identical bursts" is a distinct pathological
      EEG pattern, which in this series only occurred after diffuse cerebral ischemia
      and was invariably associated with poor outcome. SIGNIFICANCE: In comatose
      patients after cardiac arrest, "burst-suppression with identical bursts" predicts
      a poor outcome with a high specificity.

PMID- 24286856
TI  - Palmitate-induced activation of mitochondrial metabolism promotes oxidative
      stress and apoptosis in H4IIEC3 rat hepatocytes.
AB  - OBJECTIVE: Hepatic lipotoxicity is characterized by reactive oxygen species (ROS)
      accumulation, mitochondrial dysfunction, and excessive apoptosis, but the precise
      sequence of biochemical events leading to oxidative damage and cell death remains
      unclear. The goal of this study was to delineate the role of mitochondrial
      metabolism in mediating hepatocyte lipotoxicity. MATERIALS/METHODS: We treated
      H4IIEC3 rat hepatoma cells with free fatty acids in combination with antioxidants
      and mitochondrial inhibitors designed to block key events in the progression
      toward apoptosis. We then applied (13)C metabolic flux analysis (MFA) to quantify
      mitochondrial pathway alterations associated with these treatments. RESULTS:
      Treatment with palmitate alone led to a doubling in oxygen uptake rate and in
      most mitochondrial fluxes. Supplementing culture media with the antioxidant N
      acetyl-cysteine (NAC) reduced ROS accumulation and caspase activation and
      partially restored cell viability. However, (13)C MFA revealed that treatment
      with NAC did not normalize palmitate-induced metabolic alterations, indicating
      that neither elevated ROS nor downstream apoptotic events contributed to
      mitochondrial activation. To directly limit mitochondrial metabolism, the complex
      I inhibitor phenformin was added to cells treated with palmitate. Phenformin
      addition eliminated abnormal ROS accumulation, prevented the appearance of
      apoptotic markers, and normalized mitochondrial carbon flow. Further studies
      revealed that glutamine provided the primary fuel for elevated mitochondrial
      metabolism in the presence of palmitate, rather than fatty acid beta-oxidation,
      and that glutamine consumption could be reduced through co-treatment with
      phenformin but not NAC. CONCLUSION: Our results indicate that ROS accumulation in
      palmitate-treated H4IIEC3 cells occurs downstream of altered mitochondrial
      oxidative metabolism, which is independent of beta-oxidation and precedes
      apoptosis initiation.

PMID- 24286858
TI  - Generalization of improved step length symmetry from treadmill to overground
      walking in persons with stroke and hemiparesis.
AB  - OBJECTIVES: Determine whether adaptation to a swing phase perturbation during
      gait transferred from treadmill to overground walking, the rate of overground
      deadaptation, and whether overground aftereffects improved step length asymmetry
      in persons with hemiparetic stroke and gait asymmetry. METHODS: Ten participants
      with stroke and hemiparesis and 10 controls walked overground on an instrumented
      gait mat, adapted gait to a swing phase perturbation on a treadmill, then walked
      overground on the gait mat again. Outcome measures, primary: overground step
      length symmetry, rates of treadmill step length symmetry adaptation and
      overground step length symmetry deadaptation; secondary: overground gait
      velocity, stride length, and stride cycle duration. RESULTS: Step length symmetry
      aftereffects generalized to overground walking and adapted at a similar rate on
      the treadmill in both groups. Aftereffects decayed at a slower rate overground in
      participants with stroke and temporarily improved overground step length
      asymmetry. Both groups' overground gait velocity increased post adaptation due to
      increased stride length and decreased stride duration. CONCLUSIONS: Stroke and
      hemiparesis do not impair generalization of step length symmetry changes from
      adapted treadmill to overground walking, but prolong overground aftereffects.
      SIGNIFICANCE: Motor adaptation during treadmill walking may be an effective
      treatment for improving overground gait asymmetries post-stroke.

PMID- 24286860
TI  - Structural, evolutionary and functional analysis of APN genes in the Lepidoptera
      Bombyx mori.
AB  - Aminopeptidases N (APNs), the receptors of Bacillus thuringiensis (Bt) toxin in
      the lepidopteran midgut, are involved in the Bt pathogen infection mechanism. In
      the present work, we screened 102 APNs from SilkDB, ButterflyBase and
      MonarchBase; 16 APNs were identified from the silkworm (Bombyx mori) and 24 from
      the monarch butterfly (Danaus plexippus). Syntenic and phylogenetic tree analysis
      showed that APN genes have developed multi-family genes before evolutionary
      divergence of the Lepidoptera. The tissue-expression pattern shows some BmAPNs
      are specifically or highly expressed in the midgut. Bacillus bombysepticus (Bb)
      is a specific pathogen of B. mori, leading to acute fuliginosa septicemia of the
      larva. BmAPNs were modulated by real time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) analysis after Bb or Bt oral infection. There
      were different patterns of induced expression between Bb and Bt challenges,
      suggesting that B. mori has different responses to infection by the specific
      pathogen Bb and the nonspecific pathogen Bt. Research on BmAPNs will help us to
      better understand the evolutionary conservation and functions in Bb or Bt
      pathogen interaction with the host and to apply this knowledge in agricultural
      and forestry pest control.

PMID- 24286859
TI  - Neuroprotective and cognitive enhancing effects of a multi-targeted food
      intervention in an animal model of neurodegeneration and depression.
AB  - Rising neurodegenerative and depressive disease prevalence combined with the lack
      of effective pharmaceutical treatments and dangerous side effects, has created an
      urgent need for the development of effective therapies. Considering that these
      disorders are multifactorial in origin, treatments designed to interfere at
      different mechanistic levels may be more effective than the traditional single
      targeted pharmacological concepts. To that end, an experimental diet composed of
      zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3),
      docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This
      diet was tested on the olfactory bulbectomized rat (OBX), an established animal
      model of depression and cognitive decline. The ingredients of the diet have been
      individually shown to attenuate glutamate excitoxicity, exert potent anti
      oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that
      all have been implicated in neurodegenerative diseases and in the cognitive
      deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX
      surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced
      cognitive and behavioral deficits, except long-term spatial memory. Ameliorating
      effects of the diet extended to the control animals. Furthermore, the
      experimental diet reduced hippocampal atrophy and decreased the peripheral immune
      activation in the OBX rats. The ameliorating effects of the diet on the OBX
      induced changes were comparable to those of the NMDA receptor antagonist,
      memantine, a drug used for the management of Alzheimer's disease. This proof-of
      concept study suggests that a diet, which simultaneously targets multiple disease
      etiologies, can prevent/impede the development of a neurodegenerative and
      depressive disorders and the concomitant cognitive deficits. 

PMID- 24286861
TI  - Multiple service use: the impact of consistency in service quality for vulnerable
      youth.
AB  - Little is known about the way in which variations in service quality influence
      outcomes when youth are clients of more than one service system. This article
      reports on a study of 1,210 adolescents (aged 13-17 years), half were concurrent
      clients of two or more services and half were not involved in two or more
      services. Youth completed a self-report questionnaire administered by a trained
      interviewer. It was hypothesized that youth reporting two positive service
      experiences would report lower risks, higher resilience, and better outcomes than
      youth reporting inconsistent or two negative service experiences and that their
      resilience, risks, and outcomes would be similar to those of youth not involved
      in two or more services. MANCOVA was used to determine the relationship among
      service quality and resilience, risk, and outcomes with four covariates that
      assessed family and neighborhood environments, history of abuse and neglect, and
      chronic need. Results indicate that service quality had an effect on resilience,
      risks, and outcomes. These relationships were mediated quite strongly by the
      influence of the risks youth faced in their neighborhoods and to a lesser extent
      by the other three covariates. Of the three dependent variables, risk appeared to
      be the most consistently influenced by all the covariates, and it also
      differentiated service experience groups. Results point to the importance of
      services developing strategies to effectively address risks confronted by youth
      and also to ensure that when more than one service is involved with youth,
      consistency in service delivery is achieved. 

PMID- 24286862
TI  - Perioral aging--an anthropometric appraisal.
AB  - To adequately perform perioral rejuvenation procedures, it is necessary to
      understand the morphologic changes caused by facial aging. Anthropometric
      analyses of standardized frontal view and profile photographs could help to
      investigate such changes. Photographs of 346 male individuals were evaluated
      using 12 anthropometric indices. Data from two groups of health subjects, the
      first exhibiting a mean age of nearly 20 and the second of nearly 60 years, were
      compared. To evaluate the influence of combined nicotine and alcohol abuse, the
      data of the second group were compared to a third group exhibiting a similar mean
      age who were known alcohol and nicotine abusers. Comparison of the first to the
      second group showed significant decrease of the vertical height of upper and
      lower vermilion and relative enlargement of the cutaneous part of upper and lower
      lips. This effect was stronger in the upper vermilion and medial upper lips. The
      sagging of the upper lips led to the appearance of an increased mouth width. In
      the third group the effect of sagging of the upper lips, and especially its
      medial portion was significantly higher compared to the second group. The photo
      assisted anthropometric measurements investigated gave reproducible results
      related to perioral aging. 

PMID- 24286863
TI  - Virtual planning for craniomaxillofacial surgery--7 years of experience.
AB  - Contemporary computer-assisted surgery systems more and more allow for virtual
      simulation of even complex surgical procedures with increasingly realistic
      predictions. Preoperative workflows are established and different commercially
      software solutions are available. Potential and feasibility of virtual
      craniomaxillofacial surgery as an additional planning tool was assessed
      retrospectively by comparing predictions and surgical results. Since 2006 virtual
      simulation has been performed in selected patient cases affected by complex
      craniomaxillofacial disorders (n = 8) in addition to standard surgical planning
      based on patient specific 3d-models. Virtual planning could be performed for all
      levels of the craniomaxillofacial framework within a reasonable preoperative
      workflow. Simulation of even complex skeletal displacements corresponded well
      with the real surgical result and soft tissue simulation proved to be helpful. In
      combination with classic 3d-models showing the underlying skeletal pathology
      virtual simulation improved planning and transfer of craniomaxillofacial
      corrections. Additional work and expenses may be justified by increased
      possibilities of visualisation, information, instruction and documentation in
      selected craniomaxillofacial procedures. 

PMID- 24286865
TI  - Oxidative stress impairs multiple regulatory events to drive persistent cytokine
      stimulated STAT3 phosphorylation.
AB  - Although cytokine-driven STAT3 phosphorylation and activation are often
      transient, persistent activation of STAT3 is a hallmark of a range of pathologies
      and underpins altered transcriptional responses. As triggers in disease
      frequently include combined increases in inflammatory cytokine and reactive
      oxygen species levels, we report here how oxidative stress impacts on cytokine
      driven STAT3 signal transduction events. In the model system of murine embryonic
      fibroblasts (MEFs), combined treatment with the interleukin-6 family cytokine
      Leukemia Inhibitory Factor (LIF) and hydrogen peroxide (H2O2) drove persistent
      STAT3 phosphorylation whereas STAT3 phosphorylation increased only transiently in
      response to LIF alone and was not increased by H2O2 alone. Surprisingly,
      increases in transcript levels of the direct STAT3 gene target SOCS3 were delayed
      during the combined LIF + H2O2 treatment, leading us to probe the impact of
      oxidative stress on STAT3 regulatory events. Indeed, LIF + H2O2 prolonged JAK
      activation, delayed STAT3 nuclear localisation, and caused relocalisation of
      nuclear STAT3 phosphatase TC-PTP (TC45) to the cytoplasm. In exploring the
      nuclear import/ export pathways, we observed disruption of nuclear/cytoplasmic
      distributions of Ran and importin-alpha3 in cells exposed to H2O2 and the
      resultant reduced nuclear trafficking of Classical importin-alpha/3-dependent
      protein cargoes. CRM1-mediated nuclear export persisted despite the oxidative
      stress insult, with sustained STAT3 Y705 phosphorylation enhancing STAT3 nuclear
      residency. Our studies thus reveal for the first time the striking impact of
      oxidative stress to sustain STAT3 phosphorylation and nuclear retention following
      disruption of multiple regulatory events, with significant implications for STAT3
      function.

PMID- 24286864
TI  - Cytosolic functions of MORC2 in lipogenesis and adipogenesis.
AB  - Microrchidia (MORC) family CW-type zinc finger 2 (MORC2) has been shown to be
      involved in several nuclear processes, including transcription modulation and DNA
      damage repair. However, its cytosolic function remains largely unknown. Here, we
      report an interaction between MORC2 and adenosine triphosphate (ATP)-citrate
      lyase (ACLY), an enzyme that catalyzes the formation of acetyl-coA and plays a
      central role in lipogenesis, cholesterogenesis, and histone acetylation.
      Furthermore, we demonstrate that MORC2 promotes ACLY activation in the cytosol of
      lipogenic breast cancer cells and plays an essential role in lipogenesis,
      adipogenesis and differentiation of 3T3-L1 preadipocytic cells. Consistently, the
      expression of MORC2 is induced during the process of 3T3-L1 adipogenic
      differentiation and mouse mammary gland development at a stage of increased
      lipogenesis. This observation was accompanied by a high ACLY activity. Together,
      these results demonstrate a cytosolic function of MORC2 in lipogenesis,
      adipogenic differentiation, and lipid homeostasis by regulating the activity of
      ACLY. 

PMID- 24286867
TI  - Hsp90 activity is necessary to acquire a proper neuronal polarization.
AB  - Chaperones are critical for the folding and regulation of a wide array of
      cellular proteins. Heat Shock Proteins (Hsps) are the most representative group
      of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90
      role is being studied in neurodegenerative diseases, its role in neuronal
      differentiation remains mostly unknown. Since neuronal polarity mechanisms depend
      on local stability and degradation, we asked whether Hsp90 could be a regulator
      of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a
      well established model of cultured hippocampal neurons using an Hsp90 specific
      inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different
      developmental stages disturbs neuronal polarity formation or axonal elongation.
      Hsp90 inhibition during the first 3h in culture promotes multiple axon
      morphology, while this inhibition after 3h slows down axonal elongation. Hsp90
      inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a
      reduced Akt activity. In parallel, we detected an alteration of kinesin-1
      subcellular distribution. Moreover, these effects were seconded by changes in
      Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90
      activity. In conclusion, our data strongly suggests that Hsp90 activity is
      necessary to control the expression, activity or location of specific kinases and
      motor proteins during the axon specification and axon elongation processes. Even
      more, our data demonstrate the existence of a "time-window" for axon
      specification in this model of cultured neurons after which the inhibition of
      Hsp90 only affects axonal elongation mechanisms. 

PMID- 24286868
TI  - Selecting pesticides for inclusion in drinking water quality guidelines on the
      basis of detection probability and ranking.
AB  - Pesticides released into the environment may pose both ecological and human
      health risks. Governments set the regulations and guidelines for the allowable
      levels of active components of pesticides in various exposure sources, including
      drinking water. Several pesticide risk indicators have been developed using
      various methodologies, but such indicators are seldom used for the selection of
      pesticides to be included in national regulations and guidelines. The aim of the
      current study was to use risk indicators for the selection of pesticides to be
      included in regulations and guidelines. Twenty-four risk indicators were created,
      and a detection rate was defined to judge which indicators were the best for
      selection. The combination of two indicators (local sales of a pesticide for the
      purposes of either rice farming or other farming, divided by the guideline value
      and annual precipitation, and amended with the scores from the physical and
      chemical properties of the pesticide) gave the highest detection rates. In this
      case study, this procedure was used to evaluate 134 pesticides that are currently
      unregulated in the Japanese Drinking Water Quality Guidelines, from which 44 were
      selected as pesticides to be added to the primary group in the guidelines. The
      detection probability of the 44 pesticides was more than 72%. Among the 102
      pesticides currently in the primary group, 17 were selected for withdrawal from
      the group. 

PMID- 24286866
TI  - Soluble T cell immunoglobulin and mucin domain (TIM)-1 and -4 generated by A
      Disintegrin And Metalloprotease (ADAM)-10 and -17 bind to phosphatidylserine.
AB  - T cell immunoglobulin and mucin domain 1 and 4 (TIM-1 and -4) proteins serve as
      phosphatidylserine receptors to engulf apoptotic cells. Here we show that human
      TIM-1 and TIM-4 proteins are targets of A Disintegrin And Metalloprotease (ADAM)
      mediated ectodomain shedding resulting in soluble forms of TIM-1 and TIM-4. We
      identified ADAM10 and ADAM17 as major sheddases of TIM-1 and TIM-4 as shown by
      protease-specific inhibitors, the ADAM10 prodomain, siRNA and ADAM10/ADAM17
      deficient murine embryonic fibroblasts (MEFs). TIM-1 and TIM-4 lacking the
      intracellular domain were efficiently cleaved after ionomycin- and PMA-treatment,
      indicating that the intracellular domain was not necessary for ectodomain
      shedding. Soluble TIM-1 and -4 were able to bind to phosphatidylserine,
      suggesting that soluble TIM-1 and -4 might act as negative regulators of cellular
      TIM-1 and -4. In summary, we describe TIM-1 and TIM-4 as novel targets for ADAM10
      and ADAM17-mediated ectodomain shedding. 

PMID- 24286869
TI  - [Neonatal morbidity in early-term newborns].
AB  - INTRODUCTION: In the last decades has increased significantly The birth of
      children from 37 to 38 weeks of gestation, a period called early term, has
      significantly increased in the past twenty years or so, parallel to the increase
      in induced deliveries and the cesarean rate. PATIENTS AND METHOD: Retrospective
      cohorts population study, which included those babies born between 37 and 41
      weeks of gestation in the period 1992-2011 (n=35.539). This population was
      divided into two cohorts, early term newborn (RNTP) of 37-38 weeks (n=11,318),
      and full term newborn (RNTC), of 39-41 weeks of gestation (n=24,221). The rates
      of cesarean section, neonatal unit admission, respiratory morbidity, apnea and
      need for assisted ventilation, hyperbilirubinemia requiring phototherapy,
      hypoglycemia, seizures, hypoxic-ischemia encephalopathy, need for parenteral
      nutrition and early sepsis were all reviewed. RESULTS: There was a progressive
      increase in the number of caesarean sections throughout the period studied (from
      30.9% to 40.3%). The cesarean section rate was higher in RNTP than in the RNTC
      (38.3% vs 31.3%, P<.0001). On comparing the two groups, significant differences
      were found in the rate of admission to neonatal unit, 9.1% vs 3.5% (P<.0001);
      respiratory morbidity (hyaline membrane 0.14% vs 0.007% [P<.0001], transient
      tachypnea 1.71% vs 0.45% [P<.0001], mechanical ventilation 0.2% vs 0.07%
      [P<.009], continuous positive airway pressure 0.11% vs 0.01% [P<.0001]),
      phototherapy 0.29% vs 0.07% (P<.0001), hypoglycemia 0.54% vs 0.11% (P<.0001),
      parenteral nutrition 0.16% vs 0.04% (P<.0001). There were no significant
      differences in the rate of early sepsis, pneumothorax, aspiration syndromes,
      seizures and hypoxic-ischemic encephalopathy. CONCLUSIONS: In our environment,
      there is a significant number of RNTP, which have a significantly higher
      morbidity than newborns RNTC registered. After individualizing each case, it is
      essential not end a pregnancy before 39 weeks of gestation, except for maternal,
      placental or fetal conditions indicating that continuing the pregnancy may
      increase the risk for the fetus and/or the mother.

PMID- 24286870
TI  - [Unexpected finding in genetic advice].

PMID- 24286871
TI  - [Confusion as a presentation symptom of pseudomigraine with pleocytosis in a
      paediatric patient].
AB  - Transient headache and neurological deficits with cerebrospinal fluid lymphocytic
      pleocytosis (Handl) syndrome is a rare condition of unknown origin that is
      characterized by episodes of severe headache, transient neurological deficits
      that recur over less than 3 months, and lymphocytic pleocytosis in CSF. We report
      the case of a 14 year-old girl who presented with headache and vomiting that
      lasted 4 days, later combined with a clinical presentation of confusion, with a
      decrease in the level of consciousness, aphasia, peripheral facial paralysis,
      ataxia and fever for 24 hours. CSF analysis showed pleocytosis (110 cells/ml) and
      proteinorrachia (87 mg/dl). Electroencephalogram in the acute time showed
      generalized slowing, and later a focal slowing in the left hemisphere. She
      suffered 7 episodes of migraine (severe headache and vomiting) in the following
      two months, remaining asymptomatic thereafter. This is the first pediatric case
      published in the literature that presents with an agitated and/or confused state.
      This condition must be considered in the differential diagnosis of patients with
      headache and acute altered level of consciousness, in order to avoid prolonged
      treatments or unnecessary invasive testing.

PMID- 24286872
TI  - [Anti-glomerular basement membrane antibody disease: an uncommon cause of renal
      failure].

PMID- 24286873
TI  - [Management of prolonged convulsive seizures in the community: results of the
      PERFECTTM study in Spain].
AB  - INTRODUCTION: The Practices in Emergency and Rescue medication For Epilepsy
      managed with Community administered Therapy (PERFECTTM) Initiative was set up in
      2011 to gain a better understanding of how prolonged convulsive seizures are
      managed, and rescue medication is administered, in out-of-hospital settings
      across Europe. This paper explores the initial research findings for Spain.
      MATERIAL AND METHODS: A review was made of existing clinical guidelines, guidance
      to schools, and relevant policy and legal frameworks, as well as a survey of 20
      healthcare professionals who treat children with prolonged convulsive seizures in
      Spain. RESULTS: Existing clinical guidelines pertain mainly to the hospital
      setting, and contain very little information on how prolonged seizures should be
      managed outside of the hospital. Guidance for schools is unclear as to whether
      teachers are allowed to administer rescue medication to children, and there is no
      legal obligation for school staff to administer medication to children under
      their care. As a result of such uncertainty, whether or not children who
      experience prolonged seizures receive their rescue medication during school hours
      depends mostly on the resources and training available in each school.
      CONCLUSIONS: There is a need for more explicit guidance covering educational and
      healthcare settings, clearer information to parents and schools, and more
      systematic training to be made available to caregivers. This is to ensure that
      all children at risk of a prolonged convulsive seizure receive rescue medication
      in a timely manner, regardless of where their seizure occurs.

PMID- 24286874
TI  - [Results from the 2012-2013 paediatric national survey on off-label drug use in
      children in Spain (OL-PED study)].
AB  - INTRODUCTION: Off-label drug use is a common practice in paediatrics. The aim of
      the present study was to estimate the knowledge of Spaniard paediatricians on off
      label use. MATERIAL AND METHODS: Cross-sectional, multicentre, descriptive and
      national study from July 2012 to March 2013 using an on-line questionnaire on off
      label use in children. An e-mail was sent to paediatricians who were members of
      the Spanish Association of Paediatrics (AEP) or its Regional or Paediatric
      Specialties Societies. RESULTS: Out of 673 responses were received, 75.1% of
      Spanish paediatricians knew the meaning of off-label use, 61% of them prescribed
      medicines outside the conditions authorised in their Summary of Product
      Characteristics (SPC) and 47% knew of the importance of noting the off-label use
      in the medical record. However, just under half of paediatricians informed
      parents, and only 22% wrote it down in the medical record. CONCLUSIONS: Most
      Spanish paediatricians do not meet current regulations regarding off-label use.
      This regulation demands: justifying the decisions when off-label use is needed,
      and to write down in the medical record that, at least an oral consent from the
      parents has been obtained. This study reveals a fact that Spanish paediatricians
      must change. Meanwhile, it is a priority to continue with the implementation of
      consensus and clinical guidelines, to obtain more data on the efficacy and safety
      of off-label drug use in children, and to incorporate them into the SPC.

PMID- 24286875
TI  - [Retroperitoneal cystic lymphangioma].

PMID- 24286876
TI  - [Hemorrhagic infarction of the testicle after spermatic cord torsion].

PMID- 24286877
TI  - [Design and implementation of a training program given by residents in
      intermediate pediatric cardiopulmonary resuscitation for medical students].

PMID- 24286878
TI  - [The importance of nutritional history].

PMID- 24286879
TI  - [Pott's puffy tumour: a forgotten condition?].

PMID- 24286880
TI  - [Relationship between previous severity of illness and outcome of in-hospital
      cardiac arrest].
AB  - OBJECTIVES: To analyze the relationship between previous severity of illness,
      lactic acid, creatinine and inotropic index with mortality of in-hospital cardiac
      arrest (CA) in children, and the value of a prognostic index designed for adults.
      METHODS: The study included total of 44 children aged from 1 month to 18 years
      old who suffered a cardiac arrest while in hospital. The relationship between
      previous severity of illness scores (PRIMS and PELOD), lactic acid, creatinine,
      treatment with vasoactive drugs, inotropic index with return of spontaneous
      circulation and survival at hospital discharge was analyzed. RESULTS: The large
      majority (90.3%) of patients had a return of spontaneous circulation, and 59%
      survived at hospital discharge. More than two-thirds (68.2%) were treated with
      inotropic drugs at the time of the CA. The patients who died had a higher lactic
      acid before the CA (3.4 mmol/L) than survivors (1.4 mmol/L), P=.04. There were no
      significant differences in PRIMS, PELOD, creatinine, inotropic drugs, and
      inotropic index before CA between patients who died and survivors. CONCLUSION: A
      high lactic acid previous to cardiac arrest could be a prognostic factor of in
      hospital cardiac arrest in children.

PMID- 24286881
TI  - [An unusual cause of bruising].

PMID- 24286882
TI  - [Prenatal diagnosis of Apert syndrome caused by de novo mutation in FGFR2 gene].

PMID- 24286883
TI  - [Hospital admissions due to varicella in a tertiary hospital].
AB  - INTRODUCTION: Varicella (chickenpox) can cause serious complications and
      admission to hospital. Several countries included the varicella vaccine in their
      immunization schedules. MATERIAL AND METHODS: A descriptive and retrospective
      study of hospitalizations due to varicella and its complications was conducted in
      a referral center from 2005 to 2011. RESULTS: A total of 1192 children with
      varicella were seen in the emergency room, of which 99 (8.5%) required admission.
      The annual incidence of admissions due to varicella and varicella complications
      was, 19.4 and 15.3 cases per 100,000 children under 14 years, respectively.
      Complications were more common in children under 5 years (79.5%), and with no
      underlying disease (78.2%). Infection of skin and soft tissue was the most common
      complication (62%). The mean hospital stay was 4.5 days (SD 4). CONCLUSIONS:
      Varicella causes high morbidity, and is more frequent in absolute terms in
      healthy children under 5 years of age. Therefore, routine vaccination recommended
      by the Immunization Advisory Committee should be mandatory.

PMID- 24286884
TI  - [Human parechovirus-3 infection in a neonate with fever and suspected sepsis].
AB  - The human parechovirus (HPeV) are viruses of the recently described
      Picornaviridae family and are causing several infections in young children. The
      pathology associated with these viruses is beginning to emerge. The HPeV type 3,
      has been described particularly in association with sepsis-like febrile
      syndromes, meningitis and encephalitis in very young infants and neonates. We
      report the case of a 14-day-old girl with a fever and clinical sepsis that
      required hospitalization and in which HPeV-3 was identified in the cerebrospinal
      fluid. The blood, urine and cerebrospinal fluid bacterial cultures were negative,
      and the patient improved. This case illustrates the usefulness of investigating
      parechovirus infection in neonates with fever or suspected sepsis. 

PMID- 24286885
TI  - [Prevalence of ankyloglossia in newborns in Asturias (Spain)].
AB  - INTRODUCTION: The prevalence of ankyloglossia has been estimated at around 4% of
      live births. Its prevalence at national level is unknown. MATERIAL AND METHODS:
      Multicenter, prospective observational study. Six hospitals in Asturias took
      part. All newborns were examined on Sundays, Tuesdays and Thursdays for 3 months.
      Coryllos and Hazelbaker criteria were used to diagnose ankyloglossia. RESULTS:
      The prevalence in the 667 newborns examined was 12.11% (95% CI: 9.58 to 14.64),
      of whom 62% were male. One in 4 children with ankyloglossia had a family history.
      According to Coryllos' classification, type II was the most common (54%).
      CONCLUSIONS: The prevalence of ankyloglossia in Asturias was 2 to t3 times higher
      than expected. The diagnostic criteria for ankyloglossia needs to be unified, and
      further studies are required to determine the association with breastfeeding
      difficulties and other health problems.

PMID- 24286886
TI  - [Sleep apnea-hypopnea syndrome of short onset].

PMID- 24286887
TI  - [Intradiaphragmatic extralobar pulmonary sequestration].

PMID- 24286888
TI  - [Hypersensitivity pneumonitis in the school environment].

PMID- 24286889
TI  - [Prolonged delirium due to propofol sedation in an adolescent].

PMID- 24286890
TI  - [From gut to brain..., passing through the blood stream].

PMID- 24286891
TI  - [Coexistence of hemangioma and vascular malformation: a fortuitous association or
      something else?].

PMID- 24286892
TI  - Relation of autonomic and cardiac abnormalities to ventricular fibrillation in a
      rat model of epilepsy.
AB  - Cardiac autonomic, conduction, and structural changes may occur in epilepsy and
      may contribute to sudden unexpected death in epilepsy (SUDEP), e.g. by increasing
      the risk for ventricular fibrillation (VF). In a model of chronic seizures in
      rats, we sought to study (1) cardiac and autonomic derangements that accompany
      the epileptic state, (2) whether chronically seizing rats experienced more
      significant cardiac effects after severe acute seizures, and (3) the
      susceptibility of chronically seizing rats to VF arising from autonomic and
      hypoxemic changes, which commonly occur during seizures. Sprague-Dawely rats were
      injected with saline or kainic acid to induce chronic seizures. At 2-3 months or
      7-11 months after injection, these rats were studied with both 12-lead
      electrocardiography (to assess heart rate variability and QT dispersion) and
      echocardiography under ketamine/xylazine or urethane anesthesia. Hearts were
      subsequently excised, weighed, and examined histologically. Epileptic rats
      exhibited decreased vagal tone, increased QT dispersion, and eccentric cardiac
      hypertrophy without significant cardiac fibrosis, especially at 7-11 months post
      injection. Of these three findings, vagal tone was inversely correlated with
      heart weights. Epileptic rats exhibited diminished systolic function compared to
      controls after severe acute seizures. However, animals with long-standing chronic
      seizures were less susceptible to autonomic/hypoxemia-driven VF, and their
      susceptibility inversely correlated with mean left ventricular wall thickness on
      histology. On the basis of this model, we conclude that cardiac changes accompany
      epilepsy and these can lead to significant seizure-associated cardiac performance
      decreases, but these cardiac changes actually lower the probability of VF. 

PMID- 24286893
TI  - Physiotherapy students' experiences of bullying on clinical internships: a
      qualitative study.
AB  - OBJECTIVES: To consider the experiences of final-year physiotherapy students who
      have experienced workplace bullying on a clinical internship. DESIGN: Qualitative
      methodology using individual semi-structured interviews. SETTING: A university in
      the Midlands region of the UK. PARTICIPANTS: Eight undergraduate physiotherapy
      students who had experienced one incident of bullying on a clinical internship.
      MAIN OUTCOME MEASURES: Thematic analysis of semi-structured interviews. RESULTS:
      Four main themes were identified: (1) external and situational influences of
      bullying; (2) students' reactions to the experience of bullying; (3) inability to
      reveal the experience; and (4) overcoming problems. Bullying had a range of
      adverse effects on the students, with many expressing self-doubt in their
      competence and viewing their supervisor as unapproachable and unsupportive. Five
      students were not initially able to recognise the experience as bullying. In
      addition, students did not feel able to report the experience and use the support
      mechanisms in place. This may have been a result of having concerns that the
      problem would escalate if they reported the experience and, as a consequence,
      have a negative effect on their grade. Students were keen to offer a range of
      strategies for clinical practice in order to prevent bullying for future
      generations of students. CONCLUSIONS: Students' health, security and confidence
      in their ability as a physiotherapist can be at great risk from bullying. Steps
      are needed to ensure that students are better protected from bullying, and feel
      more able to address bullying behaviour during clinical internships.

PMID- 24286894
TI  - Gait analysis in a pre- and post-ischemic stroke biomedical pig model.
AB  - Severity of neural injury including stroke in human patients, as well as recovery
      from injury, can be assessed through changes in gait patterns of affected
      individuals. Similar quantification of motor function deficits has been measured
      in rodent animal models of such injuries. However, due to differences in
      fundamental structure of human and rodent brains, there is a need to develop a
      large animal model to facilitate treatment development for neurological
      conditions. Porcine brain structure is similar to that of humans, and therefore
      the pig may make a more clinically relevant animal model. The current study was
      undertaken to determine key gait characteristics in normal biomedical miniature
      pigs and dynamic changes that occur post-neural injury in a porcine middle
      cerebral artery (MCA) occlusion ischemic stroke model. Yucatan miniature pigs
      were trained to walk through a semi-circular track and were recorded with high
      speed cameras to detect changes in key gait parameters. Analysis of normal pigs
      showed overall symmetry in hindlimb swing and stance times, forelimb stance time,
      along with step length, step velocity, and maximum hoof height on both fore and
      hindlimbs. A subset of pigs were again recorded at 7, 5 and 3 days prior to MCA
      occlusion and then at 1, 3, 5, 7, 14 and 30 days following surgery. MRI analysis
      showed that MCA occlusion resulted in significant infarction. Gait analysis
      indicated that stroke resulted in notable asymmetries in both temporal and
      spatial variables. Pigs exhibited lower maximum front hoof height on the paretic
      side, as well as shorter swing time and longer stance time on the paretic
      hindlimb. These results support that gait analysis of stroke injury is a highly
      sensitive detection method for changes in gait parameters in pig.

PMID- 24286895
TI  - [Emphysematous pancreatitis].

PMID- 24286896
TI  - Memory consolidation and inducible nitric oxide synthase expression during
      different sleep stages in Parkinson disease.
AB  - BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized
      by motor and nonmotor dysfunctions, which include sleep disturbances. Rapid eye
      movement (REM) sleep is associated with numerous physiologic changes such as
      memory consolidation. Compelling evidence suggests that nitric oxide (NO) is
      crucial to both sleep regulation and memory consolidation. In our study, we
      explored changes in biologic molecules during various sleep stages and the
      effects of sleep on memory consolidation in PD. METHODS: Ten PD patients and 14
      volunteers without PD participated in our study. The gene expression of inducible
      NO synthase (iNOS) in all sleep stages was measured using realtime polymerase
      chain reaction (PCR) based on polysomnography (PSG)-guided peripheral blood
      sampling. In addition, the efficiency of memory consolidation during the sleep of
      the participants was measured using the Wechsler Memory Scale, third edition (WMS
      III). RESULTS: The iNOS expression increased in all sleep stages among the PD
      patients compared to the control participants, in whom iNOS expression decreased
      during REM sleep. Regarding memory consolidation, the performance of the controls
      in logic memory and the patients in visual reproduction tasks improved after
      sleep. CONCLUSIONS: The iNOS synthase expression was different from control
      participants among PD patients, and the expression was dissimilar in various
      sleep stages. Sleep might enhance memory consolidation and there are different
      memory consolidation profiles between PD and control participants demonstrating
      distinct memory consolidation profiles.

PMID- 24286897
TI  - Sleep disorders, sleepiness, and near-miss accidents among long-distance highway
      drivers in the summertime.
AB  - OBJECTIVE: We aimed to investigate sleepiness, sleep hygiene, sleep disorders,
      and driving risk among highway drivers. METHODS: We collected data using cross
      sectional surveys, including the Epworth Sleepiness Scale (ESS) questionnaire,
      Basic Nordic Sleep Questionnaire (BNSQ), and a travel questionnaire; we also
      obtained sleep data from the past 24 h and information on usual sleep schedules.
      Police officers invited automobile drivers to participate. RESULTS: There were
      3051 drivers (mean age, 46+/-13 y; 75% men) who completed the survey (80%
      participation rate). Eighty-seven (2.9%) drivers reported near-miss sleepy
      accidents (NMSA) during the trip; 8.5% of NMSA occurred during the past year and
      2.3% reported sleepiness-related accidents occurring in the past year. Mean
      driving time was 181+/-109 min and mean sleep duration in the past 24 h was 480+/
      104 min; mean sleep duration during workweeks was 468+/-74 min. Significant risk
      factors for NMSA during the trip were NMSA in the past year, nonrestorative sleep
      and snoring in the past 3 months, and sleepiness during the interview. Neither
      sleep time in the past 24 h nor acute sleep debt (sleep time difference between
      workweeks and the past 24 h) correlated with the occurrence of near misses.
      CONCLUSIONS: Unlike previous studies, acute sleep loss no longer explains
      sleepiness at the wheel. Sleep-related breathing disorders or nonrestorative
      sleep help to explain NMSA more adequately than acute sleep loss.

PMID- 24286898
TI  - Smartphones to the rescue.

PMID- 24286899
TI  - Authors' response.

PMID- 24286900
TI  - Sealants and demineralization.

PMID- 24286901
TI  - Ethics in orthodontics. Let the truth be known.

PMID- 24286903
TI  - Photographic and videographic assessment of the smile: objective and subjective
      evaluations of posed and spontaneous smiles.
AB  - INTRODUCTION: Esthetic considerations play an increasingly important role in
      patient care, and clinicians need a methodology that includes imaging techniques
      to capture the dynamic nature of the smile. Photographs of the posed smile are
      routinely used to guide diagnosis and treatment, but there is no standardized and
      validated method for recording the dynamic smile. The purposes of this study were
      to (1) determine whether a posed smile is reproducible, (2) compare visual and
      verbal cues in eliciting a smile, and (3) compare the diagnostic value of
      videography and photography in evaluating a patient's smile. METHODS: The smiles
      of 22 subjects were simultaneously photographed and videotaped on 2 separate
      occasions. For objective comparisons, measurements of the smile were obtained
      from 8 * 10 color still photographs and selected digitized video images. A panel
      consisting of a layperson, an oral surgeon, an orthodontist, and a prosthodontist
      subjectively assessed the reproducibility of the smile, posed vs spontaneous
      smiles, and the diagnostic value of video vs still images. RESULTS: Objective
      measurements showed that the posed smile can be reliably reproduced, whether
      captured by videography or still photography. However, subjectively, the panel
      members detected differences between the posed smiles taken on different days 80%
      of the time. The clinician panel members expressed a strong preference for
      videography over photography and for the spontaneous over the posed smiles.
      CONCLUSIONS: This study emphasizes the need to continue to investigate and
      standardize the methods of eliciting and recording a smile of diagnostic quality.

PMID- 24286904
TI  - Assessment of phantom dosimetry and image quality of i-CAT FLX cone-beam computed
      tomography.
AB  - INTRODUCTION: The increasing use of cone-beam computed tomography in orthodontics
      has been coupled with heightened concern about the long-term risks of x-ray
      exposure in orthodontic populations. An industry response to this has been to
      offer low-exposure alternative scanning options in newer cone-beam computed
      tomography models. METHODS: Effective doses resulting from various combinations
      of field of view size and field location comparing child and adult
      anthropomorphic phantoms with the recently introduced i-CAT FLX cone-beam
      computed tomography unit (Imaging Sciences, Hatfield, Pa) were measured with
      optical stimulated dosimetry using previously validated protocols. Scan protocols
      included high resolution (360 degrees  rotation, 600 image frames, 120 kV[p], 5
      mA, 7.4 seconds), standard (360 degrees , 300 frames, 120 kV[p], 5 mA, 3.7
      seconds), QuickScan (180 degrees , 160 frames, 120 kV[p], 5 mA, 2 seconds), and
      QuickScan+ (180 degrees , 160 frames, 90 kV[p], 3 mA, 2 seconds). Contrast-to
      noise ratio was calculated as a quantitative measure of image quality for the
      various exposure options using the QUART DVT phantom. RESULTS: Child phantom
      doses were on average 36% greater than adult phantom doses. QuickScan+ protocols
      resulted in significantly lower doses than standard protocols for the child (P =
      0.0167) and adult (P = 0.0055) phantoms. The 13 * 16-cm cephalometric fields of
      view ranged from 11 to 85 MUSv in the adult phantom and 18 to 120 MUSv in the
      child phantom for the QuickScan+ and standard protocols, respectively. The
      contrast-to-noise ratio was reduced by approximately two thirds when comparing
      QuickScan+ with standard exposure parameters. CONCLUSIONS: QuickScan+ effective
      doses are comparable with conventional panoramic examinations. Significant dose
      reductions are accompanied by significant reductions in image quality. However,
      this trade-off might be acceptable for certain diagnostic tasks such as interim
      assessment of treatment results.

PMID- 24286906
TI  - Comparison of 3-dimensional dental models from different sources: diagnostic
      accuracy and surface registration analysis.
AB  - INTRODUCTION: The aim of this study was to assess the diagnostic accuracy and
      surface matching characteristics of 3-dimensional digital dental models obtained
      from various sources. METHODS: Three sets of maxillary and mandibular digital
      models of 30 subjects were included in this study. Three-dimensional
      stereolithography model files were obtained from a 3-dimensional laser desktop
      scanner (Ortho-Insight 3D; Motionview Software, Hixson, Tenn), the emodel system
      (GeoDigm, Chanhassen, Minn), and cone-beam computerized tomography. Arch-length
      discrepancy measurements were made on the 3-dimensional digital models and
      compared with direct caliper measurements. Additionally, stereolithography files
      from the 3 digital model systems were paired and superimposed using a best-fit
      algorithm. Average linear differences between the stereolithography shells were
      computed together with surface correlation amounts at various tolerance levels.
      Data were evaluated using intraclass correlation coefficients and the Tukey mean
      difference test. RESULTS: Although all 3 digital model groups displayed good
      correlation with caliper measurements, the virtual scan models had the highest
      correlation with the manual method (ICC > 0.95). The Tukey mean difference test
      showed no consistent bias of one approach vs the others compared with caliper
      measurements; random errors were detected in all the comparisons. For the
      estimation of arch-length discrepancy, the mean bias of the scanned virtual
      models in comparison with caliper measurements (0.24 +/- 0.67 mm) was smaller
      than the mean biases of the emodels and the models generated from cone-beam
      computed tomography. Additionally, the best surface overlap correlation was
      observed between the virtual scanned models and the emodels. The mean linear
      distances between the stereolithography shells of these 2 model systems were 0.14
      and 0.13 mm for the maxillary and mandibular arches, respectively. CONCLUSIONS:
      All 3 digital model systems can provide diagnostic information similar to caliper
      measurements, with varying degrees of agreement limits. The scanned virtual
      models had the least mean bias. A strong surface match correlation was observed
      between the virtual scanned models and the emodels, indicating that these could
      be used interchangeably.

PMID- 24286905
TI  - Three-dimensional treatment outcomes in Class II patients treated with the Herbst
      appliance: a pilot study.
AB  - INTRODUCTION: The aims of this study were to analyze 3-dimensional skeletal
      changes in subjects with Class II malocclusion treated with the Herbst appliance
      and to compare these changes with treated Class II controls using 3-dimensional
      superimposition techniques. METHODS: Seven consecutive Herbst patients and 7
      Class II controls treated with Class II elastics who met the inclusion criteria
      had cone-beam computed tomographs taken before treatment, and either after Herbst
      removal or at posttreatment for the control subjects. Three-dimensional models
      were generated from the cone-beam computed tomography images, registered on the
      anterior cranial bases, and analyzed using color maps and point-to-point
      measurements. RESULTS: The Herbst patients demonstrated anterior translation of
      the glenoid fossae and condyles (right anterior fossa, 1.69 +/- 0.62 mm; left
      anterior fossa, 1.43 +/- 0.71 mm; right anterior condyle, 1.20 +/- 0.41 mm; left
      anterior condyle, 1.29 +/- 0.57 mm), whereas posterior displacement predominated
      in the controls (right anterior fossa, -1.51 +/- 0.68 mm; left anterior fossa, 
      1.31 +/- 0.61 mm; right anterior condyle, -1.20 +/- 0.41 mm; left anterior
      condyle, -1.29 +/- 0.57 mm; P <0.001). There was more anterior projection of B
      point in the Herbst patients (2.62 +/- 1.08 mm vs 1.49 +/- 0.79 mm; P <0.05).
      Anterior displacement of A-point was more predominant in the controls when
      compared with the Herbst patients (1.20 +/- 0.53 mm vs -1.22 +/- 0.43 mm; P
      <0.001). CONCLUSIONS: Class II patients treated with the Herbst appliance
      demonstrated anterior displacement of the condyles and glenoid fossae along with
      maxillary restraint when compared with the treated Class II controls; this might
      result in more anterior mandibular projection.

PMID- 24286907
TI  - Evaluating the agreement of skeletal age assessment based on hand-wrist and
      cervical vertebrae radiography.
AB  - INTRODUCTION: The aim of this study was to examine the agreement of skeletal age
      assessment based on hand-wrist radiographs with cephalogram-based cervical
      vertebrae evaluation. To circumvent bias and loss of information from staging, a
      quantitative approach was applied to determine morphologic changes. METHODS: We
      analyzed 730 sets of radiographs (cephalogram and hand-wrist) of untreated
      subjects (352 boys, 378 girls; age range, 6-18 years) from a growth study, each
      sex as a separate sample. Skeletal age was determined on the hand-wrist
      radiographs according to the method of Greulich and Pyle. Morphometric changes of
      the vertebral bodies C2 through C4 were measured (concavity, anterior height, and
      angle) and tested for correlations with the method of Greulich and Pyle. All
      correlating variables were included in a multiple linear regression to generate a
      calculated skeletal age. To establish the agreement between the method of
      Greulich and Pyle and calculated skeletal age, Bland-Altman plots were made,
      limits of agreement were identified, and cross-tables (before and after peak
      height velocity) were computed. Similarly, the agreement between the method of
      Greulich and Pyle and each subject's chronologic age was estimated for
      comparison. RESULTS: Concavity of C2, C3, and C4; anterior height of C3 and C4;
      and the angle of C3 correlated with skeletal age highly significantly (P <0.0001)
      in both sexes, and calculated skeletal age was established based on a linear
      regression. The agreement between the method of Greulich and Pyle and calculated
      skeletal age was modest (limits of agreement: boys, +/-3.5 years; girls, +/-3.3
      years) and substantially weaker than the agreement between the method of Greulich
      and Pyle and chronologic age (limits of agreement: boys, +2.1 to -1.7 years;
      girls, +2.2 to -1.2 years). Similarly, calculated skeletal age resulted in
      considerably more false predictions of peak height velocity (boys, 18.9%; girls,
      12.9%) than did chronologic age (boys, 7.1%; girls, 7.4%). CONCLUSIONS:
      Morphometric assessment of age-dependent changes in the cervical spine offers no
      advantage over chronologic age, in either assessing skeletal age or predicting
      the pubertal growth spurt.

PMID- 24286908
TI  - Cone-beam computed tomography evaluation of alveolar ridge width and height
      changes after orthodontic space opening in patients with congenitally missing
      maxillary lateral incisors.
AB  - INTRODUCTION: The purpose of this study was to evaluate the alveolar bone
      dimensional changes with cone-beam computed tomography after space-opening
      procedures for an endosseous implant in patients with unilateral or bilateral
      maxillary lateral incisor agenesis. METHODS: A pilot retrospective cohort study
      was conducted of 11 patients (13 sites) in whom the canines had erupted less than
      2 mm distally to the central incisors. Pretreatment and posttreatment scans
      obtained from 3 private practice offices were evaluated for changes in alveolar
      bone width, height, and labial concavity. A fiducial line representing the ideal
      location of the longitudinal axis of an endosseous dental implant was used as a
      reference for the spatial location of the alveolar bone at the lateral incisor
      site in reference to the adjacent tooth roots at posttreatment. The posttreatment
      width and height measurements scans were compared with normative data from the
      contralateral incisor in patients with unilateral agenesis (n = 6). RESULTS:
      Alveolar bone width was significantly decreased on average from 17% to 25% along
      the height of the ridge (2-10 mm) (P <0.05). The labial concavity was
      significantly increased compared with the initial dimensions (P <0.05). No
      significant changes were found in alveolar bone ridge height. CONCLUSIONS:
      Significant alveolar bone width decreases and increases in labial concavity were
      found after implant ridge development in patients with maxillary lateral incisor
      agenesis. The alveolar bone ridge was located more lingually than the adjacent
      teeth, suggesting a need for bone grafting to achieve proper fixture placement.

PMID- 24286909
TI  - Craniofacial and upper airway morphology in pediatric sleep-disordered breathing
      and changes in quality of life with rapid maxillary expansion.
AB  - INTRODUCTION: The association between pediatric sleep-disordered breathing caused
      by upper airway obstruction and craniofacial morphology is poorly understood and
      contradictory. The aims of this study were to evaluate the prevalence of children
      at risk for sleep-disordered breathing, as identified in an orthodontic setting
      by validated screening questionnaires, and to examine associations with their
      craniofacial and upper airway morphologies. A further aim was to assess the
      change in quality of life related to sleep-disordered breathing for affected
      children undergoing rapid maxillary expansion to correct a palatal crossbite or
      widen a narrow maxilla. METHODS: A prospective case-control study with children
      between 8 and 17 years of age (n = 81) at an orthodontic clinic was undertaken.
      The subjects were grouped as high risk or low risk for sleep-disordered breathing
      based on the scores from a validated 22-item Pediatric Sleep Questionnaire and
      the Obstructive Sleep Apnea-18 Quality of Life Questionnaire. Variables
      pertaining to a screening clinical examination, cephalometric assessment, and
      dental cast analysis were tested for differences between the 2 groups at
      baseline. Ten children who underwent rapid maxillary expansion were followed
      longitudinally until removal of the appliance approximately 9 months later with a
      repeated Obstructive Sleep Apnea-18 Quality of Life Questionnaire. All data were
      collected blinded to the questionnaire results. RESULTS: The frequency of palatal
      crossbite involving at least 3 teeth was significantly higher in the high-risk
      group at 68.2%, compared with the low-risk group at 23.2% (P <0.0001). Average
      quality of life scores in the high-risk group indicated reduced quality of life
      related to sleep-disordered breathing by 16% compared with children in the low
      risk group at baseline (P <0.0001). Cephalometrically, mean inferior airway
      space, posterior nasal spine to adenoidal mass distance, and adenoidal mass to
      soft palate distance were reduced in the high-risk group compared with the low
      risk group by 1.87 mm (P <0.03), 2.82 mm (P <0.04), and 2.13 mm (P <0.03),
      respectively. The mean maxillary intercanine, maxillary interfirst premolar,
      maxillary interfirst molar, mandibular intercanine, and mandibular interfirst
      premolar widths were reduced in the high-risk group compared with the low-risk
      group by 4.22 mm (P <0.0001), 3.92 mm (P <0.0001), 4.24 mm (P <0.0001), 1.50 mm
      (P <0.01), and 1.84 mm (P <0.01), respectively. Children treated with rapid
      maxillary expansion showed an average improvement of 14% in quality of life
      scores in the high-risk group compared with the low-risk group, which showed a
      slight worsening in quality of life related to sleep-disordered breathing by an
      average of 1% (P <0.04), normalizing the quality of life scores in the high-risk
      children to the baseline scores compared with the low-risk group. CONCLUSIONS:
      Children at high risk for sleep-disordered breathing are characterized by reduced
      quality of life, reduced nasopharyngeal and oropharyngeal sagittal dimensions,
      palatal crossbite, and reduced dentoalveolar transverse widths in the maxillary
      and mandibular arches. No sagittal or vertical craniofacial skeletal
      cephalometric predictors were identified for children at high risk for sleep
      disordered breathing. In the short term, rapid maxillary expansion might aid in
      improvement of the quality of life for children with a narrow maxilla in the
      milder end of the sleep-disordered breathing spectrum.

PMID- 24286910
TI  - Bullying among Jordanian schoolchildren, its effects on school performance, and
      the contribution of general physical and dentofacial features.
AB  - INTRODUCTION: The aims of this study were to investigate the experience of
      bullying in a representative sample of Jordanian schoolchildren in Amman, to look
      at its effect on school attendance and perception of academic performance, and to
      look at the contribution of general physical and dentofacial features to this
      phenomenon. METHODS: This was a cross-sectional study in which a representative
      sample of sixth-grade students (11-12 years of age) from randomly selected
      schools was asked to complete questionnaires distributed in the classroom in the
      presence of the researchers. The final sample size was 920 children (470 girls,
      450 boys). RESULTS: The prevalence of bullying was 47% (n = 433); significantly
      more boys reported being bullied than girls (P <0.001). The percentage of
      students subjected to name-calling was 40.9%. A significantly greater proportion
      of victims of bullying reported playing truant from school and disliking school
      than those who were not bullied. Teeth were the number 1 feature targeted for
      bullying, followed by strength and weight. The 3 most commonly reported
      dentofacial features targeted by bullies were spacing between the teeth or
      missing teeth, shape or color of the teeth, and prominent maxillary anterior
      teeth. CONCLUSIONS: This study demonstrated a high prevalence of bullying in
      Jordanian schools, with many children experiencing bullying because of their
      dental or facial appearance.

PMID- 24286911
TI  - Sequential piezocision: a novel approach to accelerated orthodontic treatment.
AB  - Piezocision-assisted orthodontic treatment is an innovative, minimally invasive
      surgical technique designed to help achieve rapid orthodontic tooth movement.
      Microsurgical interproximal openings are made in the buccal gingivae to let the
      piezoelectric knife create the bone injury that will lead to transient
      demineralization and subsequent accelerated tooth movement. When this procedure
      was first described, cuts were made simultaneously at the maxilla and the
      mandible. In recent years, the technique has evolved to a more staged approach,
      with selected areas or segments of the arch demineralized at different times
      during orthodontic treatment to help achieve specific results. The purpose of
      this article was to report the use of sequential piezocision in the correction of
      a Class III malocclusion, in a total treatment time of 8 months. 

PMID- 24286912
TI  - Orthodontic treatment of a patient with Duchenne muscular dystrophy and
      macroglossia: how informed consent was critical to success.
AB  - This article describes the complex orthodontic treatment of a 22-year-old patient
      with Duchenne muscular dystrophy and macroglossia. His orthodontic treatment
      hinged on providing proper informed consent and management of the malocclusion
      with glossectomy, extractions, fixed appliances, and elastics. Challenges to
      traditional treatment are outlined, and compromises to both process and outcome
      are discussed from an informed consent point of view because of the serious risks
      involved. The treatment objectives were met, and the outcome was considered a
      success. 

PMID- 24286913
TI  - Orthodontic treatment considerations for a patient with erythropoietic
      protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an inherited blood disorder in which
      formation of the heme group of hemoglobin is defective. Specifically, a
      deficiency of the enzyme ferrochelatase leads to the accumulation of
      protoporphyrin, resulting in often painful photosensitivity of the skin and
      tissues. The prevalence of EPP is estimated at 1:75,000 to 1:200,000.
      Photosensitivity is exhibited upon exposure to light with specific wavelengths
      through the creation of reactive oxygen products (oxidants), activation of the
      complement system, and mast cell degranulation. The aim of this article is to
      report the orthodontic treatment of an 11-year-old boy with EPP, a Class III
      skeletal relationship, and an anterior crossbite. Orthodontic treatment
      established normal overbite and overjet. Short-term periodontal and dental tissue
      responses to treatment were noted. Extra care was needed when collecting
      photographic and radiographic records for this patient and during some treatment
      procedures to avoid causing a photosensitive reaction of the skin or oral mucosa.

PMID- 24286914
TI  - Apicotomy: surgical management of maxillary dilacerated or ankylosed canines.
AB  - This clinical article reports a technique, apicotomy, for managing dilacerated or
      ankylosed canines. The records of 3 patients successfully treated with apicotomy
      are presented. Orthodontists observe clinically significant incidences of
      impacted maxillary canines in their daily practices. Several procedures have been
      described to bring an ankylosed, impacted tooth into occlusion. Luxation is the
      most widely used solution, but there are risks involved with that approach, and
      the success rate is low. Surgical repositioning has also been used, but morbidity
      is high, and the aggressiveness of the procedure might also contraindicate it.
      Ankylosis might be related to the anatomic position of the canine's root apex and
      its adjacent anatomic structures. Apicotomy is a guided fracture of a canine root
      apex, followed by its orthodontic traction. It is a conservative surgical
      alternative for treating impacted canines with dilacerations or apical root
      ankylosis. 

PMID- 24286915
TI  - Diagnostic accuracy of impression-free digital models.
AB  - INTRODUCTION: Impression-free techniques might eliminate the potential
      shortcomings of digital dental models. Chairside scanners offer the advantage of
      obtaining digital dental models directly from the patient without the need for
      dental impressions. The aim of this study was to evaluate the accuracy of 3
      dimensional digital models acquired from a chairside intraoral scanner compared
      with both manual and cone-beam computed tomography measurements of the same
      dental anatomy. METHODS: The study sample comprised 60 dry skulls. Each skull had
      the maxillary and mandibular arches scanned with a Cadent iTero scanner (Align
      Technology, San Jose, Calif) and had a cone-beam computed tomography scan taken
      with a CS 9300 unit (Carestream Health, Atlanta, Ga). Linear measurements in all
      3 dimensions of the space in each dental arch together with tooth-size arch
      length analysis for both the maxillary and mandibular arches were carried out
      manually on the dry skulls with calipers and digitally on the scanned 3
      dimensional models and cone-beam computed tomography images. Intraclass
      correlation (ICC) analysis was performed for all variables tested in the study
      groups, with the manual measurements on the dry skulls as the gold standard. The
      Bland-Altman analysis was also applied to the data to graphically display the
      agreement of the diagnostic measurements obtained from these methods. RESULTS:
      Measurements from the iTero models demonstrated near-perfect agreement (ICC, 0.91
      0.99) with the caliper measurements. Cone-beam computed tomography measurements
      had moderate to high levels of agreement (ICC, 0.65-0.99) compared with the
      caliper measurements. CONCLUSIONS: Direct digital acquisition of the dental
      arches with a chairside scanner provided almost 1-to-1 diagnostic information of
      the investigated anatomy and was superior to the cone-beam computed tomography
      measurements.

PMID- 24286916
TI  - Litigation and legislation. The cost of care vs the standard of care.

PMID- 24286917
TI  - Analyzing longitudinal orthodontic data. Part 4: Latent growth curve models.

PMID- 24286918
TI  - [The French reference sites of the European Innovation Partnership on active and
      healthy ageing].

PMID- 24286920
TI  - Reconstruction of limbal stem cell deficient corneal surface with induced human
      bone marrow mesenchymal stem cells on amniotic membrane.
AB  - The cornea can be damaged by a variety of clinical disorders or chemical,
      mechanical, and thermal injuries. The objectives of this study were to induce
      bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue
      engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface
      defects in a limbal stem cell deficiency model. BMSCs were induced to corneal
      lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation
      of corneal stem cell markers; beta1-integrin, C/EBPdelta, ABCG2, and p63,
      increased protein expression of CK3 and p63 significantly compared with the
      uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on
      amniotic membrane in a transwell co-culture system and were grown in limbal
      medium. Limbal stem cell deficiency models were induced by alkaline injury, and
      the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed
      remarkable improvement in corneal regeneration in terms of corneal clarity and
      reduced vascularization. Histologic and optical coherence tomography analyses
      demonstrated comparable corneal thickness and achieved stratified epithelium with
      a compact stromal layer resembling that of normal cornea. CK3 and p63 were
      expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced
      into corneal epithelial lineage, and these cells are viable for the formation of
      TEC, to be used for the reconstruction of the corneal surface in the limbal stem
      cell deficient model. 

PMID- 24286919
TI  - Regenerative medicine in Alzheimer's disease.
AB  - Identifying novel, effective therapeutics for Alzheimer's disease (AD) is one of
      the major unmet medical needs for the coming decade. Because the current paradigm
      for developing and testing disease-modifying AD therapies is protracted and
      likely to be even longer, with the shift toward earlier intervention in
      preclinical AD, it is an open issue whether we can develop, test, and widely
      deploy a novel therapy in time to help the current at-risk generation if we
      continue to follow the standard paradigms of discovery and drug development.
      There is an imperative need to find safe and effective preventive measures that
      can be distributed rapidly to stem the coming wave of AD that will potentially
      engulf the next generation. We can define regenerative medicine broadly as
      approaches that use stem cell-based therapies or approaches that seek to modulate
      inherent neurogenesis. Neurogenesis, although most active during prenatal
      development, has been shown to continue in several small parts of the brain,
      including the hippocampus and the subventricular zone, suggesting its potential
      to reverse cognitive deficits. If AD pathology affects neurogenesis, then it
      follows that conditions that stimulate endogenous neurogenesis (eg, environmental
      stimuli, physical activity, trophic factors, cytokines, and drugs) may help to
      promote the regenerative and recovery process. Herein, we review the complex
      logistics of potentially implementing neurogenesis-based therapeutic strategies
      for the treatment of AD. 

PMID- 24286921
TI  - Boosting the aerodynamic properties of vibrating-mesh nebulized polymeric
      nanosuspensions.
AB  - Pulmonary application of drug-loaded polymeric nanosuspensions is achieved by
      vibrating-mesh nebulizers, which allow for an output of intact nanocarriers from
      the nebulizer reservoir. However, adequate aerosol droplet sizes are a
      prerequisite for an efficient pulmonary deposition. The current study discloses
      experimental findings useful to optimize the aerodynamic characteristics of
      formulations atomized by the vibrating-mesh nebulizers Aeroneb((r)) Pro and
      eFlow((r))rapid. Parameters with significant influence on the aerosol droplet
      diameter were identified by a statistical design analysis rating size results
      from laser diffraction. Subsequently, the effect of selected biocompatible
      solutes on the aerodynamic performance of nebulized formulations was studied and
      correlated with their physicochemical properties. Vibrating-mesh generated
      aerosols were significantly affected by the dynamic viscosity and conductivity of
      the applied formulation. Consequently, an increase in viscosity enhancer (sucrose
      and poly(ethylene glycol)) or electrolyte (NaCl and CaCl2) content caused the
      droplet diameter to decrease. Similarly, purified nanosuspensions revealed a
      considerable decline in aerosol particle size upon excipient addition. However,
      coating of polymeric nanoparticles with poloxamer and poly(vinyl alcohol) was
      necessary to avoid electrolyte-induced nanoparticle aggregation. Overall, the
      current study emphasizes that supplementation of nanosuspensions with
      biocompatible solutes is an excellent means to tailor the characteristics of
      aerosols generated by vibrating-mesh technology. 

PMID- 24286922
TI  - Intranasal delivery of streptomycin sulfate (STRS) loaded solid lipid
      nanoparticles to brain and blood.
AB  - Factors like unreliable and poor oral absorption, including an active Pgp-efflux
      point towards a compromised oral bioavailability (BA) of streptomycin sulfate
      (STRS). Latter instigates its parenteral use (i.m.) only. Furthermore, its
      chronic use leads to serious side effects like nephrotoxicity and ototoxicity. In
      the present study, we propose to develop streptomycin sulfate (STRS) loaded solid
      lipid nanoparticles (STRS-SLNs) for non-invasive intranasal (IN) delivery. STRS
      SLNs were prepared using patented nanocolloidal aqueous dispersion technique
      (Indian Patent application 3093/DEL/2012). Small particle size (140.1+/-7.0 nm)
      and significant entrapment efficiency (54.83+/-2.1%) was achieved.
      Biodistribution studies using (99m)Tc showed a 3.15 and 11.0 times higher
      concentrations in the brain and blood of mice, respectively, on IN administration
      of STRS-SLNs in comparison to free (F)-STRS. Lower concentrations (3.3 times) in
      kidneys implicate lower nephrotoxicity. Similarly a 12 and 4 times lower levels
      of drug in liver and spleen, respectively upon administration of STRS-SLNs as
      compared to F-STRS also indicate its lesser accumulation in these
      reticuloendothelial system organs. Lipophillic enclosure imparted to STRS,
      coupled with small particle size, and its purported ability to inhibit Pgp-efflux
      due to the presence of tween 80, is considered to be responsible for a better BA
      shown by STRS upon incorporation into SLNs. This is predicted to result in an
      effective treatment of all types of tuberculosis including cerebral tuberculosis
      as indicated by high relative distribution to brain in comparison to free-STRS.

PMID- 24286923
TI  - Dynamic in vivo imaging of dual-triggered microspheres for sustained release
      applications: synthesis, characterization and cytotoxicity study.
AB  - This paper deals with the synthesis, characterization and property evaluation of
      drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell.
      The synthetic procedure consists of 3 steps, of which the first two comprise the
      synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a
      shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and
      divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to
      the formation of magnetic nanoparticles on the microsphere's surface. AA that
      attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the
      inner and the outer surface of the microspheres, enhance the efficacy of this
      intelligent drug delivery system (DDS), which constitutes a promising approach
      toward cancer therapy. A number of experimental techniques were used to
      characterize the resulting microspheres. In order to investigate the in vitro
      controlled release behavior of the synthesized microspheres, we studied the Dox
      release percentage under different pH conditions and under external magnetic
      field. Hyperthermia caused by an alternating magnetic field (AFM) is used in
      order to study the doxorubicin (Dox) release behavior from microspheres with pH
      functionality. The in vivo fate of these hybrid-microspheres was tracked by
      labeling them with the gamma-emitting radioisotope (99m)Tc after being
      intravenously injected in normal mice. According to our results, microsphere
      present a pH depending and a magnetic heating, release behavior. As expected,
      labeled microspheres were mainly found in the mononuclear phagocyte system (MPS).
      The highlights of the current research are: (i) to illustrate the advantages of
      controlled release by combining hyperthermia and pH-sensitivity and (ii) to
      provide noninvasive, in vivo information on the spatiotemporal biodistribution of
      these microsphere by dynamic gamma-imaging. 

PMID- 24286924
TI  - Gene therapy and DNA delivery systems.
AB  - Gene therapy is a promising new technique for treating many serious incurable
      diseases, such as cancer and genetic disorders. The main problem limiting the
      application of this strategy in vivo is the difficulty of transporting large,
      fragile and negatively charged molecules like DNA into the nucleus of the cell
      without degradation. The key to success of gene therapy is to create safe and
      efficient gene delivery vehicles. Ideally, the vehicle must be able to remain in
      the bloodstream for a long time and avoid uptake by the mononuclear phagocyte
      system, in order to ensure its arrival at the desired targets. Moreover, this
      carrier must also be able to transport the DNA efficiently into the cell
      cytoplasm, avoiding lysosomal degradation. Viral vehicles are the most commonly
      used carriers for delivering DNA and have long been used for their high
      efficiency. However, these vehicles can trigger dangerous immunological
      responses. Scientists need to find safer and cheaper alternatives. Consequently,
      the non-viral carriers are being prepared and developed until techniques for
      encapsulating DNA can be found. This review highlights gene therapy as a new
      promising technique used to treat many incurable diseases and the different
      strategies used to transfer DNA, taking into account that introducing DNA into
      the cell nucleus without degradation is essential for the success of this
      therapeutic technique. 

PMID- 24286925
TI  - Effect of nitrate addition on reductive transformation of pentachlorophenol in
      paddy soil in relation to iron(III) reduction.
AB  - Reductive dechlorination is a crucial pathway for anaerobic biodegradation of
      highly chlorinated organic contaminants. Under an anoxic environment, reductive
      dechlorination of organic contaminants can be affected by many redox processes
      such as nitrate reduction and iron reduction. In the present study, batch
      incubation experiments were conducted to investigate the effect of nitrate
      addition on reductive dechlorination of PCP in paddy soil with consideration of
      iron transformation. Study results demonstrate that low concentrations (0, 0.5
      and 1 mM) of nitrate addition can enhance the reductive dechlorination of PCP and
      Fe(III) reduction, while high concentrations (5, 10, 20 and 30 mM) of nitrate
      addition caused the contrary. Significant positive correlations between PCP
      degradation rates and the formation rates of dissolved Fe(II) (pearson
      correlation coefficients r = 0.965) and HCl-extractable Fe(II) (r = 0.921)
      suggested that Fe(III) reduction may enhance PCP dechlorination. Furthermore,
      consistent variation trends of PCP degradation and the abundances of the genus
      Comamonas, capable of Fe(III) reduction coupled to reductive dechlorination, and
      of the genus Dehalobacter indicated the occurrence of microbial community
      variation induced by nitrate addition as a response to PCP dechlorination. 

PMID- 24286926
TI  - The Leishmania chromosome lottery.

PMID- 24286928
TI  - Developmental transitions of Coxiella burnetii grown in axenic media.
AB  - Coxiella burnetii undergoes a biphasic developmental cycle within its host cell
      that generates morphologically and physiologically distinct large cell variants
      (LCV) and small cell variants (SCV). During the lag phase of the C. burnetii
      growth cycle, non-replicating SCV differentiate into replicating LCV that in turn
      differentiate back into SCV during stationary phase. Nearly homogeneous SCV are
      observed in infected Vero cells after extended incubation (21 to 28days). In the
      current study, we sought to establish whether C. burnetii developmental
      transitions in host cells are recapitulated during host cell-free (axenic) growth
      in first and second generation acidified citrate cysteine media (ACCM-1 and ACCM
      2, respectively). We show that ACCM-2 supported developmental transitions and
      viability. Although ACCM-1 also supported SCV to LCV transition, LCV to SCV
      transition did not occur after extended incubation (21days). Instead, C. burnetii
      exhibited a ghost-like appearance with bacteria containing condensed chromatin
      but otherwise devoid of cytoplasmic content. This phenotype correlated with a
      near total loss in viability between 14 and 21days of cultivation.
      Transcriptional profiling of C. burnetii following 14days of incubation revealed
      elevated expression of oxidative stress genes in ACCM-1 cultivated bacteria. ACCM
      2 differs from ACCM-1 by the substitution of methyl-beta-cyclodextrin (Mbeta-CD)
      for fetal bovine serum. Addition of Mbeta-CD to ACCM-1 at 7days post-inoculation
      rescued C. burnetii viability and lowered expression of oxidative stress genes.
      Thus, Mbeta-CD appears to alleviate oxidative stress in ACCM-2 to result in C.
      burnetii developmental transitions and viability that mimic host cell-cultivated
      organisms. Axenic cultivation of C. burnetii in ACCM-2 and new methods of genetic
      manipulation now allow investigation of the molecular basis of C. burnetii
      biphasic development. 

PMID- 24286929
TI  - [Does repeated endometrial destruction procedure decrease abnormal uterine
      bleeding, and does it reduce the number of hysterectomies in this indication?].
AB  - OBJECTIVE: Hysteroscopic endometrial resection or destruction in the indication
      of abnormal uterine bleeding or post-menopausal bleeding represents an
      alternative to hysterectomy, as it carries a lower morbidity rate. In case of
      failure of such procedure though, hysterectomy will most often be proposed as a
      second line of treatment. The place of the repetition of an endometrial
      destruction procedure has not yet been evaluated. The aim of our study is to
      evaluate the efficiency and the satisfaction after two consecutive techniques of
      endometrial destruction in case of abnormal uterine bleeding or post-menopausal
      bleeding. MATERIAL AND METHODS: Nineteen patients presenting with recurring
      abnormal uterine bleeding after one procedure of endometrial destruction,
      underwent in our department, between 2004 and 2011, a second conservative
      endometrial procedure. RESULTS: No complication occurred during the repeated
      procedure. Sixteen of the nineteen patients (84.2 %) included answered a
      questionnaire. The mean delay since the second procedure was 27 months [25; 29].
      Eight patients (i.e. 50 %) later underwent a hysterectomy, with 5 of them (31.25
      % of all 16 patients) being directly attributed to treatment failure. Patients
      said to be satisfied with the management of their condition in 68.75 % of cases,
      and 93.75 % of them would recommend it to a friend. CONCLUSION: Our results
      suggest that a second conservative management in case of recurrence of AUB is
      effective. Hysterectomy could be avoided in 50 % of cases. A second conservative
      treatment could be an interesting option for patients with medical contra
      indication for heavier surgery, as well as for patients willing to keep their
      uterus.

PMID- 24286927
TI  - A Legionella effector modulates host cytoskeletal structure by inhibiting actin
      polymerization.
AB  - Successful infection by the opportunistic pathogen Legionella pneumophila
      requires the collective activity of hundreds of virulence proteins delivered into
      the host cell by the Dot/Icm type IV secretion system. These virulence proteins,
      also called effectors modulate distinct host cellular processes to create a
      membrane-bound niche called the Legionella containing vacuole (LCV) supportive of
      bacterial growth. We found that Ceg14 (Lpg0437), a Dot/Icm substrate is toxic to
      yeast and such toxicity can be alleviated by overexpression of profilin, a
      protein involved in cytoskeletal structure in eukaryotes. We further showed that
      mutations in profilin affect actin binding but not other functions such as
      interactions with poly-l-proline or phosphatidylinositol, abolish its suppressor
      activity. Consistent with the fact the profilin suppresses its toxicity,
      expression of Ceg14 but not its non-toxic mutants in yeast affects actin
      distribution and budding of daughter cells. Although Ceg14 does not detectably
      interact with profilin, it co-sediments with filamentous actin and inhibits actin
      polymerization, causing the accumulation of short actin filaments. Together with
      earlier studies, these results reveal that multiple L. pneumophila effectors
      target components of the host cytoskeleton.

PMID- 24286930
TI  - [Regret following hysteroscopic tubal sterilization].
AB  - INTRODUCTION: The definitive contraception techniques are irreversible. Women
      opting for this type of contraception may therefore regret their decision later.
      Since 2002, the number of tubal sterilizations performed by the Essure((r))
      technique has steadily increased to more than 100,000 procedures to date. Due to
      the simplicity of the technique, the low operative risk and the absence of
      anesthesia, in most cases hysteroscopic sterilization is now the first tubal
      sterilization technique in France. The rate of regret after hysteroscopic tubal
      sterilization has never been evaluated. The purpose of this study is to evaluate
      the regret after hysteroscopic sterilization with Essure((r)). METHODS: All
      patients who benefited hysteroscopic sterilization by Essure((r)), in two
      teaching departments of obstetrics and gynecology of the same university, between
      June 2005 and December 2011 were included in this study. Patients with a medical
      indication for tubal sterilization or patients with an obturation of hydrosalpinx
      before in vitro fertilization were excluded. A specific questionnaire to assess
      patients regret was sent by post to all patients. RESULTS: During the study
      period, 452 hysteroscopic sterilizations were performed. Three hundred and six
      patients (67%) completed and returned the questionnaire. The average age of
      patients at the procedure was 41.4 [39.1, 43.7]. Mean follow after sterilization
      was 43 months [40.1, 45.9]. Seventeen of 306 patients (5.5%) expressed a sense of
      regret after sterilization. Seven women out of 306 (2.3%) consulted to discuss
      the possibility of a new pregnancy. None of these patients has finally resorted
      either to adopt or to medically assisted procreation. CONCLUSION: The regret
      after tubal sterilization by hysteroscopy is a rare event. All patients asking
      for a permanent contraception technique should be informed of the irreversible
      nature of the technique.

PMID- 24286931
TI  - Skeletal deformities in mucolipidosis III.

PMID- 24286932
TI  - Multiple vertebral metastases with fluid-fluid levels.

PMID- 24286933
TI  - Characterization of knee osteoarthritis in Latin America. A comparative analysis
      of clinical and health care utilization in Argentina, Brazil, and Mexico.
AB  - BACKGROUND: The burden of knee osteoarthritis (OA) in Latin America is unknown.
      OBJECTIVE: To determine the demographic, clinical, and therapeutic
      characteristics of patients with OA in Argentina, Brazil, and Mexico. MATERIAL
      AND METHODS: This is an observational, cross-sectional study of patients with
      symptomatic knee OA referred from first care medical centers to Rheumatology
      departments. RESULTS: We included 1210 patients (Argentina 398, Brazil 402,
      Mexico 410; mean age 61.8 [12] years; 80.8% females). Knee OA pain lasted for 69
      months; the duration and severity of the last episode were 190 days and (SD 5.2
      [3.3]; 74% had functional limitations, but very few patients lost their job
      because of knee OA. Around 71% had taken medications, but 63% relied on their own
      pocket to afford knee OA cost. Most demographic and clinical variables differed
      across countries, particularly the level of pain, disability, treatment, and
      access to care. The variable country of origin influenced the level of pain,
      disability, and NSAIDs use in logistic regression models; age, pain, treatment,
      and health care access influenced at least 2 of the models. CONCLUSIONS: The
      burden of knee OA in Latin American depends on demographic, clinical, and
      therapeutic variables. The role of such variables differs across countries. The
      level of certain variables is significantly influenced by country of origin and
      health care system.

PMID- 24286934
TI  - Angle change of the parent arteries after stent-assisted coil embolization of
      wide-necked intracranial bifurcation aneurysms.
AB  - AIM: To investigate the angle changes of the parent arteries after stent-assisted
      coil embolization of wide-necked intracranial bifurcation aneurysms. MATERIALS
      AND METHODS: The adjacent parent arterial angles before and after stent-assisted
      coil embolization were measured in 38 patients with aneurysms of the anterior
      communicating artery (ACoAA) and 41 patients with bifurcation aneurysms of the
      middle cerebral artery (MCABA). Variables were analysed in relation to the angle
      changes. RESULTS: Vascular angles of the parent arteries significantly increased
      by 27.8 degrees  (+/-18.5 degrees ) immediately after stent-assisted coil
      embolization in 79 cases (p < 0.001), with 25.7 degrees  (+/-14.8 degrees ) in
      ACoAA and 29.7 degrees  (+/-21.4 degrees ) in MCABA, respectively. In 51 (64.6%)
      cases with follow-up angiography (mean interval 13.5 +/- 4.1 months), vascular
      angles increased by 27.2 degrees  (+/-17.1 degrees ) immediately after treatment
      and further increased by 20.7 degrees  (+/-14.3 degrees ) at the last follow-up
      (all p < 0.001). More acute pre-stent angles of the parent arteries correlated
      with greater post-stent angle changes (p = 0.006). Younger age tended to be
      inversely related to post-stent angle changes (p = 0.091). CONCLUSION: Stent
      placement during coil embolization induced significant changes in the aneurysm
      parent artery relationship. Further study is needed to elicit the association
      between angle change of the parent arteries and aneurysmal stability after coil
      embolization.

PMID- 24286935
TI  - Quantitative evaluation of vertebral marrow adipose tissue in postmenopausal
      female using MRI chemical shift-based water-fat separation.
AB  - AIM: To investigate the feasibility of assessing vertebral marrow adipose tissue
      using a magnetic resonance imaging (MRI) chemical shift-based water-fat
      separation technique at 3 T. MATERIAL AND METHODS: A modified Dixon technique was
      performed to obtain the vertebral marrow fat fraction (FF) in a study of 58
      postmenopausal females (age range 49.2-77.4 years), including 24 normal bone
      density, 19 osteopaenia, and 15 osteoporosis as documented with dual-energy X-ray
      absorptiometry. The reliability of FF measurements performed by two radiologists
      independently was evaluated with the intraclass correlation coefficient (ICC).
      Ten participants were scanned twice to assess the reproducibility of FF
      measurements. FF values were compared between each vertebral level and between
      groups. RESULTS: The mean coefficient of variation of FF measurements was 2.1%.
      According to the ICC, the measurements were reliable (ICC = 0.900 for normal bone
      density, ICC = 0.937 for osteopaenia and ICC = 0.909 for osteoporosis, p < 0.001
      for all). There was an inverse association between mean FF at L1-L4 vertebrae and
      lumbar spine BMD (r = -0.459, p = 0.006), which remained significant even after
      controlling for confounders (age, height, and body weight). FF values at
      different vertebral levels were significantly correlated to each other (r = 0.703
      0.921, p < 0.05 for all). There was a general trend toward increased marrow
      adiposity for more inferior vertebral bodies. Patients with osteopaenia and
      osteoporosis had a higher marrow fat content compared with normal bone mass after
      adjusting for confounders, although no significant differences in each vertebral
      level and average marrow fat content were found between the osteopaenia and
      osteoporosis groups. CONCLUSION: Chemical shift-based water-fat separation
      enables the quantitation of vertebral marrow adiposity with excellent
      reproducibility, which appears to be a useful method to provide complementary
      information to osteoporosis-related research fields.

PMID- 24286937
TI  - Immobilization of bile salt hydrolase enzyme on mesoporous SBA-15 for co
      precipitation of cholesterol.
AB  - We describe herein a simple and effective strategy for immobilization of bile
      salt hydrolase enzyme by grafting glutaraldehyde groups inside channels of APTES
      functionalized SBA-15. The increase in glutaraldehyde concentration prevents
      leakage of enzyme but showed a steep decrease in enzyme activity in the
      immobilized matrix. So the degree of cross-linking should be the minimum possible
      to ensure sufficient stability without loss of activity. Cross-linking carried
      out with 0.1% glutaraldehyde concentration showed the highest activity, so this
      was used in all further experiments. Physico-chemical characterizations of the
      immobilized enzyme were carried out by XRD, N2 adsorption, TEM, FTIR and (29)Si
      CP-MAS NMR techniques. Immobilized BSH exhibits enhanced stability over a wide pH
      (3-11) and temperature range (40-80  degrees C) and retains an activity even
      after recycling experiments and six months of storage. From our in vivo research
      experiment toward co-precipitation of cholesterol, we have shown that immobilized
      BSH enzyme may be the promising catalyst for the reduction of serum cholesterol
      levels in our preliminary investigation. Enhancement in pH stability at the
      extreme side of pH may favor the use of immobilized BSH enzyme for drug delivery
      purpose to with stand extreme pH conditions in the gastrointestinal conditions.

PMID- 24286936
TI  - Isoproterenol effects evaluated in heart slices of human and rat in comparison to
      rat heart in vivo.
AB  - Human response to isoproterenol induced cardiac injury was evaluated by gene and
      protein pathway changes in human heart slices, and compared to rat heart slices
      and rat heart in vivo. Isoproterenol (10 and 100MUM) altered human and rat heart
      slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study
      (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal
      to mild necrosis at 24 and 48h. In the rat and the human heart, isoproterenol
      altered pathways for apoptosis/necrosis, stress/energy, inflammation, and
      remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase,
      while the in vivo rat heart exhibited necrosis histologically and further
      progression of tissue remodeling. In human heart slices genes for several heat
      shock 70kD members were altered, indicative of stress to mitigate apoptosis. The
      stress response included alterations in energy utilization, fatty acid
      processing, and the up-regulation of inducible nitric oxide synthase, a marker of
      increased oxidative stress in both species. Inflammation markers linked with
      remodeling included IL-1alpha, Il-1beta, IL-6 and TNFalpha in both species.
      Tissue remodeling changes in both species included increases in the TIMP
      proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with
      cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis,
      and Reg3b a growth factor for cardiac repair. This study demonstrates that the
      initial human heart slice response to isoproterenol cardiac injury results in
      apoptosis, stress/energy status, inflammation and tissue remodeling at
      concentrations similar to that in rat heart slices. 

PMID- 24286938
TI  - Percutaneous microwave ablation of hepatic tumors: prospective evaluation of
      postablation syndrome and postprocedural pain.
AB  - PURPOSE: To prospectively investigate the frequency and severity of postablation
      syndrome (PAS) and postprocedural pain in a cohort of patients undergoing hepatic
      microwave ablation. MATERIALS AND METHODS: From March 2009 to November 2011, 54
      consecutive patients undergoing microwave ablation for liver tumors were
      enrolled. A questionnaire was administered to investigate PAS and pain at 1, 7,
      and 40 days after ablation. Four patients did not complete all three
      questionnaires and were excluded from the analysis. Additionally, laboratory
      tests with results known to significantly increase or decrease after ablation
      were performed, and ablation parameters were recorded. Potential predictors of
      PAS and pain at 1 and 7 days were evaluated by a logistic regression model.
      RESULTS: Fifty patients underwent a single microwave ablation session, 33 for
      hepatocellular carcinoma (HCC) and 17 for liver metastasis. Median ablation
      volumes on computed tomography were 31 cm(3) for HCC and 42 cm(3) for metastasis.
      Sixty percent of patients experienced PAS in the first week. Aspartate
      aminotransferase (AST) levels after ablation were significantly associated with
      PAS during postprocedure days 1-7. Median visual analog scale scores for pain at
      the puncture site were 1 and 0.24 at 1 and 7 days, respectively. The risk of
      having at least moderate pain in the first week was significantly related to
      ablation volume and time and postablation increase in AST level. CONCLUSIONS: The
      incidence and severity of PAS with hepatic microwave ablation is similar to that
      reported for radiofrequency ablation, with the best predictive factor being
      postablation AST level elevation. Postablation pain was best predicted by total
      ablation volume and AST level.

PMID- 24286939
TI  - Safety and efficacy of transcatheter arterial embolization for lower
      gastrointestinal bleeding: a single-center experience with 112 patients.
AB  - PURPOSE: To assess the safety and efficacy of transcatheter arterial embolization
      for lower gastrointestinal bleeding (LGIB) and to determine the prognostic
      factors that affect clinical outcome. MATERIALS AND METHODS: All patients
      diagnosed with LGIB by angiography at a single institution from April 2006 to
      January 2013 were included in a retrospective study. The rates of technical
      success, early recurrent bleeding, major complications, clinical success, and in
      hospital mortality for transcatheter arterial embolization were determined. The
      influence of possible prognostic factors on the outcome was analyzed. RESULTS: A
      total of 112 patients were included (36 with small-bowel LGIB, 36 with colon
      LGIB, and 40 with rectal LGIB). N-butyl cyanoacrylate (NBCA) was the embolic
      agent for 84 patients (75.0%), whereas gelatin sponge pledgets (n = 20),
      microcoils (n = 2), polyvinyl alcohol particles with adjunctive gelatin sponge
      pledgets (n = 1), and blood clots (n = 1) were used in the other patients. The
      technical success rate was 96.4%. For the entire group, the rates of early
      recurrent bleeding, major complications, clinical success, and in-hospital
      mortality were 17.4%, 4.6%, 74.5%, and 25.0%, respectively. These were 15.2%,
      4.8%, 75.3%, and 26.2%, respectively, in the NBCA group. Hematologic malignancy,
      immobilization status, and coagulopathy were significant prognostic factors for
      clinical outcomes. CONCLUSIONS: Transcatheter arterial embolization is a safe and
      effective treatment for LGIB. NBCA could be used as a primary embolic agent for
      this procedure.

PMID- 24286940
TI  - Evaluating patency rates of an ultralow-porosity expanded polytetrafluoroethylene
      covered stent in the treatment of venous stenosis in arteriovenous dialysis
      circuits.
AB  - PURPOSE: To evaluate the efficacy of an ultralow-porosity expanded
      polytetrafluoroethylene (ePTFE) covered stent in the treatment of autogenous
      arteriovenous fistula (AVF) and prosthetic arteriovenous graft (AVG) venous
      outflow stenoses. MATERIALS AND METHODS: Clinical and angiographic outcomes of 20
      consecutive patients with arteriovenous dialysis circuits treated with the
      endoprosthesis were reviewed following institutional review board approval.
      Patients were followed routinely at 2 months and 6 months after stent placement,
      or earlier if clinically warranted. The primary endpoint was 2- and 6-month
      primary treatment area patency. Secondary endpoints included primary circuit
      patency, primary assisted patency, and secondary patency. RESULTS: Eleven
      patients with AVFs and nine patients with AVGs were treated successfully with the
      covered stent. Primary treatment area patency rates were 85% +/- 16 at both 2
      months and 6 months. Primary circuit patency rates were was 65% +/- 21 and 45% +/
      22, respectively; primary assisted patency rates were 90% +/- 13 and 85% +/- 16,
      respectively; and secondary patency rates were 100% and 90% +/- 13, respectively.
      Of the three cases of lost primary treatment area patency, two developed
      thrombosis and one developed recurrent stenosis. No significant differences were
      found between patients with AVFs and AVGs. CONCLUSIONS: Data from this
      preliminary study suggests that the ultralow-porosity ePTFE covered stent may be
      a clinically viable option for treatment of venous outflow stenoses in
      arteriovenous vascular access circuits.

PMID- 24286941
TI  - Know your market: use of online query tools to quantify trends in patient
      information-seeking behavior for varicose vein treatment.
AB  - PURPOSE: To analyze Internet search data to characterize the temporal and
      geographic interest of Internet users in the United States in varicose vein
      treatment. MATERIALS AND METHODS: From January 1, 2004, to September 1, 2012, the
      Google Trends tool was used to analyze query data for "varicose vein treatment"
      to identify individuals seeking treatment information for varicose veins. The
      term "varicose vein treatment" returned a search volume index (SVI), representing
      the search frequency relative to the total search volume during a specific time
      interval and region. Linear regression analysis and Kruskal-Wallis one-way
      analysis of variance were employed to characterize search results. RESULTS:
      Search traffic for varicose vein treatment increased by 520% over the 104-month
      study period. There was an annual mean increase of 28% (range, -18%-100%;
      standard deviation [SD], 35%), with a statistically significant linear increase
      in average yearly SVI over time (R(2) = 0.94, P < .0001). All years showed
      positive growth in mean SVI except for 2008 (18% decrease). There were
      statistically significant differences in SVI by month (Kruskal-Wallis, P < .0001)
      with significantly higher mean SVI compared with other months in May (190%
      increase; range, 26%-670%; SD, 15%) and June (209% increase; range, 35%-700%; SD,
      20%). The southern United States showed significantly higher search traffic than
      all other regions (Tukey-Kramer, P < .00001). CONCLUSIONS: There have been
      significant increases in Internet search traffic related to varicose vein
      treatment in the past 8 years. Reflected in this trend is an annual peak in
      search traffic in the late spring months with an overall geographic bias toward
      southern states. Rigorous analysis of Internet search queries for medical
      procedures may prove useful to guide the efficient use of limited resources and
      marketing dollars.

PMID- 24286942
TI  - [Radiation doses in radiology and exposure to electromagnetic fields.
      Presentation].

PMID- 24286943
TI  - Predictors of cognition in first episode psychosis.
AB  - PURPOSE: Cognitive deficits are common in the first episode of psychosis (FEP)
      and may begin much earlier. While some evidence suggests that the decline in
      cognition occurs over the untreated symptomatic period, including the prodromal
      phase, others point to these deficits being present even earlier. We aimed to
      investigate the differential effect of untreated symptomatic and pre-morbid
      phases on cognition in a large sample of FEP. METHODS: Two hundred and sixty
      eight FEP patients, admitted into a specialized early intervention service, were
      administered neuro-cognitive tests. The Circumstances of Onset and Relapse
      Schedule (CORS) was administered for measurement of duration of untreated
      psychosis (DUP), the duration of untreated illness (DUI) and demographic factors.
      The Pre-morbid Adjustment Scale (PAS) was used to measure different domains of
      pre-morbid adjustment. Seventy three healthy controls were also recruited for
      neuro-cognitive comparison. RESULTS: We observed no effect of DUP and a minimal
      effect of DUI on cognitive functioning in FEP. Instead, the early educational pre
      morbid adjustment domain was most strongly associated with cognition and
      predicted both global cognitive and verbal memory outcome in FEP. CONCLUSION: Our
      results suggest that symptoms associated with the symptomatic phase of a FEP do
      not influence cognitive functioning in FEP. Instead, cognitive deficits in FEP
      may predate illness onset and may indicate susceptibility to such illness.

PMID- 24286944
TI  - A nasal mucocele originating from complex facial fractures.
AB  - Mucoceles are benign, epithelial-lined mucous cysts. Commonly mucoceles form
      secondary to obstruction of a sinus outflow tract or from mucosal gland
      entrapment from chronic infection, inflammation, iatrogenic trauma, external
      trauma, or neoplasm. We present a rare case of a nasal mucocele in a 37-year old
      male arising from a remote history of maxillofacial trauma. To our knowledge,
      mucoceles associated with nasal bone fractures have not been reported in the
      literature. 

PMID- 24286945
TI  - Hypoglycemia.
AB  - Hypoglycemia remains a common problem for patients with diabetes and is
      associated with substantial morbidity and mortality. This article summarizes our
      current knowledge of the epidemiology, pathogenesis, risk factors, and
      complications of hypoglycemia in patients with diabetes and discusses prevention
      and treatment strategies. 

PMID- 24286946
TI  - Diabetic ketoacidosis and hyperglycemic hyperosmolar state.
AB  - Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) are
      potentially fatal hyperglycemic crises that occur as acute complications of
      uncontrolled diabetes mellitus. The authors provide a review of the current
      epidemiology, precipitating factors, pathogenesis, clinical presentation,
      evaluation, and treatment of DKA and HHS. The discovery of insulin in 1921
      changed the life expectancy of patients with diabetes mellitus dramatically.
      Today, almost a century later, DKA and HHS remain significant causes of morbidity
      and mortality across different countries, ages, races, and socioeconomic groups
      and a significant economic burden for society. 

PMID- 24286947
TI  - Advanced glycation endproducts in diabetes and diabetic complications.
AB  - This review presents insights from studies of advanced glycation end products
      (AGEs) in humans and mice. Although the emphasis is on the effects of exogenous
      AGEs and the suppression of specific host defense mechanisms, AGEs are also
      formed intracellularly, where they may contribute to several normal intracellular
      functions. It is only when the overall levels of AGEs in the extracellular and
      the intracellular spaces exceeds the ability of the native antioxidant (and AGE)
      defenses that they pose a problem. 

PMID- 24286948
TI  - Diabetic retinopathy: current concepts and emerging therapy.
AB  - More Americans become blind each year from microvascular complications of
      diabetes than from any other cause. Several studies have indicated that tight
      glucose control and lifestyle modification can dramatically reduce the incidence
      and prevalence of diabetic retinopathy. Research over the past several years has
      yielded a tremendous increase in our knowledge of the pathogenesis of the damage
      to the retina that occurs in diabetes and has facilitated our ability to
      intervene and control the damage. New intravitreal medical therapies supported by
      government- and industry-supported research are gradually replacing standard
      laser photocoagulation for the treatment of all forms of retinopathy. 

PMID- 24286949
TI  - Diabetic neuropathy.
AB  - Diabetic neuropathy (DN) is the most common and troublesome complication of
      diabetes mellitus, leading to the greatest morbidity and mortality and resulting
      in a huge economic burden for diabetes care. The clinical assessment of diabetic
      peripheral neuropathy and its treatment options are multifactorial. Patients with
      DN should be screened for autonomic neuropathy, as there is a high degree of
      coexistence of the two complications. A review of the clinical assessment and
      treatment algorithms for diabetic neuropathy, painful neuropathy, and autonomic
      dysfunction is provided. 

PMID- 24286951
TI  - Gastrointestinal complications of diabetes.
AB  - This review provides an overview of the vast gastrointestinal tract complications
      of diabetes that can occur from the mouth to the anus. The presentation,
      diagnosis, and management of gastrointestinal disorders, ranging from
      gastroparesis, celiac disease, and bacterial overgrowth to nonalcoholic fatty
      liver disease, are reviewed to heighten awareness. When managing care of patients
      with diabetes, one should keep in mind the potential gastrointestinal
      complications, as well as the frequent disorders that are not related to
      diabetes. 

PMID- 24286952
TI  - Complications of the diabetic foot.
AB  - The diabetic foot is at high risk for complications because of its role in
      ambulation. Peripheral neuropathy and peripheral vascular disease can lead to
      chronic foot ulcers, which are at high risk for infection, in part attributable
      to areas of high pressure caused by lack of tolerance of the soft tissue and bone
      and joint deformity. If left untreated, infection and ischemia lead to tissue
      death, culminating in amputation. Treatment strategies include antibiosis,
      topical therapies, offloading, debridement, and surgery. A multidisciplinary team
      approach is necessary in the prevention and treatment of complications of the
      diabetic foot. 

PMID- 24286950
TI  - Diabetic kidney disease and the cardiorenal syndrome: old disease, new
      perspectives.
AB  - In this article, the literature is reviewed regarding the role of blood pressure
      variability and nocturnal nondipping of blood pressure as well as the presence of
      diabetic kidney disease (DKD), in the absence of albuminuria, as risk predictors
      for progressive DKD. The importance of glycemic and blood pressure control in
      patients with diabetes and chronic kidney disease, and the use of oral
      hypoglycemic agents and antihypertensive agents in this patient cohort, are also
      discussed. 

PMID- 24286953
TI  - Periodontitis: oral complication of diabetes.
AB  - Periodontitis is a common, chronic, inflammatory disease in which the supporting
      apparatus of the teeth is gradually destroyed, resulting in tooth mobility and
      tooth loss. Susceptibility to periodontitis is increased approximately three-fold
      in people with diabetes. Hyperglycemia leads to exacerbated tissue destruction
      and the clinical signs of periodontitis. There is evidence to support a two-way
      relationship between periodontitis and diabetes; not only does diabetes increase
      the risk for periodontitis, but periodontitis is associated with compromised
      glycemic control. Cooperation between health care teams would benefit the
      treatment of patients with diabetes and periodontitis. 

PMID- 24286954
TI  - Dermatologic manifestations of diabetes mellitus: a review.
AB  - Diabetes mellitus affects every organ of the body including the skin. Certain
      skin manifestations of diabetes are considered cutaneous markers of the disease,
      whereas others are nonspecific conditions that occur more frequently among
      individuals with diabetes compared with the general population. Diabetic patients
      have an increased susceptibility to some bacterial and fungal skin infections,
      which account, in part, for poor healing. Skin complications of diabetes provide
      clues to current and past metabolic status. Recognition of cutaneous markers may
      slow disease progression and ultimately improve the overall prognosis by enabling
      earlier diagnosis and treatment. 

PMID- 24286955
TI  - Reproductive sequelae of diabetes in male patients.
AB  - Diabetes mellitus (DM) is an increasingly prevalent public health concern. A
      recent study projected the number of people worldwide with DM to increase from
      171 million in 2000 to 366 million in 2030. Although DM is a systemic disease
      that often leads to end-organ dysfunction of multiple body systems, the effects
      of the condition on male fertility are often not fully appreciated. DM is
      associated with multiple risk factors for reduced male fertility potential,
      including erectile dysfunction, various manifestations of ejaculatory
      dysfunction, and hypogonadism. 

PMID- 24286956
TI  - Diabetes and the female reproductive system.
AB  - The insulin/insulin-like growth factor (IGF) pathways and glucose metabolism act
      as mediators of human ovarian function and female fertility. In normal insulin
      action, insulin binds to its own receptors in the ovary to mediate
      steroidogenesis and act as a co-gonadotropin. Insulin with other factors may
      influence ovarian growth and cyst formation. The IGF pathway also seems to
      influence normal ovarian function. Insulin signaling affects reproductive
      function. Dysregulation of this pathway leads to altered puberty, ovulation, and
      fertility. Better understanding of the normal physiology and pathophysiology of
      insulin, IGF, and glucose effects on the human reproductive system will allow for
      better outcomes. 

PMID- 24286957
TI  - Complications of diabetes therapy.
AB  - Current strategies for the treatment of type 2 diabetes mellitus promote
      individualized plans to achieve target glucose levels on a patient-by-patient
      basis while minimizing treatment related risks. Maintaining glycemic control over
      time is a significant challenge because of the progressive nature of diabetes as
      a result of declining beta-cell function. This article identifies complications
      of non-insulin treatments for diabetes. The major classes of medications are
      reviewed with special focus on target population, mechanism of action, effect on
      weight, cardiovascular outcomes and additional class-specific side effects
      including effects on bone. Effects on beta-cell function are also highlighted. 

PMID- 24286958
TI  - Endocrinology and Metabolism Clinics of North America. Acute and chronic
      complications of diabetes. Foreword.

PMID- 24286959
TI  - Why focus on complications?

PMID- 24286960
TI  - Evaluation of an Enhanced Role-Based Access Control model to manage information
      access in collaborative processes for a statewide clinical education program.
AB  - BACKGROUND: Managing information access in collaborative processes is a critical
      requirement to team-based biomedical research, clinical education, and patient
      care. We have previously developed a computation model, Enhanced Role-Based
      Access Control (EnhancedRBAC), and applied it to coordinate information access in
      the combined context of team collaboration and workflow for the New York State
      HIV Clinical Education Initiative (CEI) program. We report in this paper an
      evaluation study to assess the effectiveness of the EnhancedRBAC model for
      information access management in collaborative processes when applied to CEI.
      METHODS: We designed a cross-sectional study and performed two sets of
      measurement: (1) degree of agreement between EnhancedRBAC and a control system
      CEIAdmin based on 9152 study cases, and (2) effectiveness of EnhancedRBAC in
      terms of sensitivity, specificity, and accuracy based on a gold-standard with 512
      sample cases developed by a human expert panel. We applied stratified random
      sampling, partial factorial design, and blocked randomization to ensure a
      representative case sample and a high-quality gold-standard. RESULTS: With the
      kappa statistics of four comparisons in the range of 0.80-0.89, EnhancedRBAC has
      demonstrated a high level of agreement with CEIAdmin. When evaluated against the
      gold-standard, EnhancedRBAC has achieved sensitivities in the range of 97-100%,
      specificities at the level of 100%, and accuracies in the range of 98-100%.
      CONCLUSIONS: The initial results have shown that the EnhancedRBAC model can be
      effectively used to manage information access in the combined context of team
      collaboration and workflow for coordination of clinical education programs.
      Future research is required to perform longitudinal evaluation studies and to
      assess the effectiveness of EnhancedRBAC in other applications.

PMID- 24286961
TI  - The evolution of coronary stents: a brief review.
AB  - Percutaneous coronary intervention is the most prevalent method for coronary
      artery revascularization. Initial interventions using balloon angioplasty had
      limited efficacy because coronary dissections, arterial recoil, and neointimal
      formation led to high rates of abrupt vessel closure and clinical restenosis.
      With the introduction of coronary stents, vascular dissections were stabilized
      and arterial recoil was eliminated, but neointimal accumulation remained
      problematic, resulting in the development of in-stent restenosis (ISR) in 20%-30%
      of cases. Drug-eluting stents (DESs) were developed to release antiproliferative
      agents at the site of arterial injury to attenuate neointimal formation. Although
      DESs have incrementally improved outcomes after percutaneous coronary
      intervention, delayed re-endothelialization and stent thrombosis remain important
      challenges. Herein we review the pathophysiology of ISR, stent thrombosis, and
      briefly summarize the clinical evidence behind first- and second-generation DESs.
      Moreover, we discuss advancements in our understanding of the pathogenesis of ISR
      and potential novel therapeutic strategies to improve clinical outcomes. 

PMID- 24286963
TI  - Indigenous knowledge of medicinal plants in Kotli Sattian, Rawalpindi district,
      Pakistan.
AB  - AIM OF STUDY: The present study aimed to report the ethnomedicinal information
      from Kotli Sattian, district Rawalpindi for detailed medicinal uses and to inform
      the community about conservation of medicinal plant diversity and ethnomedicinal
      knowledge of plants. MATERIAL AND METHODS: Ethnomedicinal data were collected via
      Rapid Appraisal Approach (RAA) along with interview, group meetings with local
      people having awareness about medicinal knowledge of plants and individual
      meetings with local healers. RESULTS AND DISCUSSIONS: This study reported eighty
      seven (87) indigenous medicinal plants, distributed among fifty five (55)
      families and seventy nine (79) genera. Among these, herbs contributed 43%, trees
      28%, shrubs 21% and climbing plants 8%. About 34% of herbal preparations were
      made from whole plants followed by the leaves (27%), fruits (08%), bark (06%),
      seeds (05%), root (05%), rhizome (04%), stem, flower, gum, pod and tubers (02%)
      and milky latex (01%). Justicia adhatoda showed the maximum use value (0.91)
      while Cuscuta reflexa showed the least use value (0.11). CONCLUSION: Elder people
      in the study area still rely on herbal remedies although the modern heath care
      facilities are present in the study area; thus, the indigenous plants remain
      important medicines in solving health problems.

PMID- 24286962
TI  - A refined-JinQi-JiangTang tablet ameliorates prediabetes by reducing insulin
      resistance and improving beta cell function in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Refined-JQ (JQ-R) is a mixture of refined
      extracts from three major herbal components of JinQi-JiangTang tablet: Coptis
      chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae), and Lonicera
      japonica (Caprifoliaceae). Our previous studies have indicated that JQ-R could
      decrease fasting blood glucose levels in diabetic mice and insulin resistance
      mice. Investigating the hypoglycemic effect of JQ-R on prediabetes has practical
      application value for preventing or delaying insulin resistance, impaired glucose
      tolerance and possibly the development of clinical diabetes. MATERIALS AND
      METHODS: The anti-diabetic potential of JQ-R was investigated using a high fat
      diet (HFD)-induced obesity mouse model. C57BL/6J mice (HFD-C57 mice) were fed
      with high-fat diet for 4 months. HFD-C57 mice were treated with either JQ-R
      (administered intragastrically once daily for 4 weeks) or metformin (as positive
      control), and the effects of JQ-R on body weight, blood lipids, glucose
      metabolism, insulin sensitivity, and beta cell function were monitored. RESULTS:
      The body weight, serum cholesterol, and the Homeostasis Model Assessment ratio
      (insulin resistance index) were significantly reduced in JQ-R or metformin
      treated mice, and the glucose tolerance was enhanced and insulin response was
      improved simultaneously. Moreover, both JQ-R and metformin could activate liver
      glycogen syntheses even under a relatively high glucose loading. Although
      glyconeogenesis was inhibited in the metformin treated mice, it was not observed
      in JQ-R treated mice. Similar to metformin, JQ-R could also improve the glucose
      infusion rate (GIR) in hyperglycemic clamp test. JQ-R was also shown to increase
      the levels of phosphorylated AMPKalpha and phosphorylated acetyl CoA carboxylase
      (ACC), similar to metformin. CONCLUSION: JQ-R could reduce HFD-induced insulin
      resistance by regulating glucose and lipid metabolism, increasing insulin
      sensitivity through activating the AMPK signaling pathway, and subsequently
      improving beta cell function. Therefore, JQ-R may offer an alternative in
      treating disorders associated with insulin resistance, such as prediabetes and
      T2DM.

PMID- 24286964
TI  - Simplified progressive approach for the ablation of scar related atrial
      macroreentrant tachycardias.
AB  - INTRODUCTION: Radiofrequency ablation of scar related right atrial flutter is
      challenging. Long procedures, prolonged fluoroscopic times and high percentages
      of recurrences are of concern. We present a simple and progressive approach based
      on a single electroanatomic map of the right atrium. METHODS: Twenty-two
      consecutive patients with atrial flutter and history of cardiac surgery were
      included. An electrophysiologic study was performed to define localization (left
      or right) and cavo-tricuspid isthmus participation using entrainment mapping.
      After a critical isthmus was localized, ablation was performed with an external
      irrigated tip catheter with a power limit of 30 W. Potential ablation sites were
      confirmed by entrainment. RESULTS: The predominant cardiopathy was atrial septal
      defect. All arrhythmias were localized in the right atrium; mean cycle length of
      the clinical flutter was 274 +/- 31 ms. Only 40% had cavo-tricuspid isthmus
      participation. None of the patients with successful ablation had recurrences
      after 13 +/- 9.4 months of follow-up. CONCLUSIONS: A progressive approach with
      only one activation/voltage CARTO((r)) map of the atrium and ablation of all
      potential circuits is a highly effective method for ablating scar related
      macroreentrant atrial arrhythmias.

PMID- 24286965
TI  - Continuous glucose monitoring in acute coronary syndrome.
AB  - BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular
      disease. OBJECTIVE: To compare the efficacy of devices for continuous glucose
      monitoring and capillary glucose monitoring in hospitalized patients with acute
      coronary syndrome using the following parameters: time to achieve normoglycemia,
      period of time in normoglycemia, and episodes of hypoglycemia. METHODS: We
      performed a pilot, non-randomized, unblinded clinical trial that included 16
      patients with acute coronary artery syndrome, a capillary or venous blood glucose
      >= 140 mg/dl, and treatment with a continuous infusion of fast acting human
      insulin. These patients were randomized into 2 groups: a conventional group, in
      which capillary measurement and recording as well as insulin adjustment were made
      every 4h, and an intervention group, in which measurement and recording as well
      as insulin adjustment were made every hour with a subcutaneous continuous
      monitoring system. Student's t-test was applied for mean differences and the X(2)
      test for qualitative variables. RESULTS: We observed a statistically significant
      difference in the mean time for achieving normoglycemia, favoring the
      conventional group with a P = 0.02. CONCLUSION: Continuous monitoring systems are
      as useful as capillary monitoring for achieving normoglycemia.

PMID- 24286966
TI  - Does treatment fidelity predict client outcomes in 12-Step Facilitation for
      stimulant abuse?
AB  - OBJECTIVE: This study examined the relationships between treatment fidelity and
      treatment outcomes in a community-based trial of a 12-Step Facilitation (TSF)
      intervention. METHOD: In a prior multi-site randomized clinical trial, 234
      participants in 10 outpatient drug treatment clinics were assigned to receive the
      Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention. A secondary
      analysis reviewed and coded all STAGE-12 sessions for fidelity to the protocol,
      using the Twelve Step Facilitation Adherence Competence Empathy Scale (TSF ACES).
      Linear mixed-effects models tested the relationship between three fidelity
      measures (adherence, competence, empathy) and six treatment outcomes (number of
      days of drug use and five Addiction Severity Index (ASI) composite scores)
      measured at 3 months post-baseline. RESULTS: Adherence, competence and empathy
      were robustly associated with improved employment status at follow up. Empathy
      was inversely associated with drug use, as was competence in a non-significant
      trend (p=.06). Testing individual ASI drug composite score items suggested that
      greater competence was associated with fewer days of drug use and, at the same
      time, with an increased sense of being troubled or bothered by drug use.
      CONCLUSIONS: Greater competence and empathy in the delivery of a TSF intervention
      were associated with better drug use and employment outcomes, while adherence was
      associated with employment outcomes only. Higher therapist competence was
      associated with lower self-report drug use, and also associated with greater self
      report concern about drug use. The nature of TSF intervention may promote high
      levels of concern about drug use even when actual use is low.

PMID- 24286967
TI  - Drinking motives as prospective predictors of outcome in an intervention trial
      with heavily drinking HIV patients.
AB  - BACKGROUND: Heavy alcohol consumption in HIV patients is an increasing health
      concern. Applying the drinking motivational model to HIV primary care patients,
      drinking motives (drinking to cope with negative affect, for social facilitation,
      and in response to social pressure) were associated with alcohol consumption at a
      baseline interview. However, whether these motives predict continued heavy
      drinking or alcohol dependence in this population is unknown. METHODS:
      Participants were 254 heavy-drinking urban HIV primary care patients (78.0% male;
      94.5% African American or Hispanic) participating in a randomized trial of brief
      drinking-reduction interventions. Drinking motive scales, as well as measures of
      alcohol consumption and alcohol dependence, were administered at baseline.
      Consumption and dependence measures were re-administered at the end of treatment
      two months later. Regression analyses tested whether baseline drinking motive
      scale scores predicted continued heavy drinking and alcohol dependence status at
      the end of treatment, and whether motives interacted with treatment condition.
      RESULTS: Baseline drinking to cope with negative affect predicted continued heavy
      drinking (p<0.05) and alcohol dependence, the latter in both in the full sample
      (adjusted odds ratio [AOR]=2.14) and among those with baseline dependence
      (AOR=2.52). Motives did not interact with treatment condition in predicting
      alcohol outcomes. CONCLUSIONS: Drinking to cope with negative affect may identify
      HIV patients needing targeted intervention to reduce drinking, and may inform
      development of more effective interventions addressing ways other than heavy
      drinking to cope with negative affect.

PMID- 24286968
TI  - Reduced ventral medial prefrontal cortex (vmPFC) volume and impaired vmPFC
      default mode network integration in codeine-containing cough syrups users.
AB  - OBJECTIVE: To characterize the association between clinical symptoms and
      anatomical and functional cerebral deficits in codeine-containing cough syrups
      (CCS) users using voxel-based morphometry and resting state functional
      connectivity analysis. METHODS: Participants were 30 CCS users and 30 matched
      controls. Both groups were scanned using a volumetric three-dimensional fast
      field echo sequence and a gradient-echo echo-planar imaging sequence. Impulsivity
      traits of both groups were evaluated with the Barratt Impulsiveness Scale 11 (BIS
      11). Voxel-based morphometry was used to characterize gray matter (GM) deficits
      in CCS users. The clinical significance of regional volume reduction was
      investigated by evaluating its association with impulsivity in CCS users and with
      alterations in resting state functional connectivity when brain regions with GM
      volume reduction were used as seed areas. RESULTS: Significantly decreased GM
      volume was observed in CCS users in bilateral ventral medial prefrontal cortex
      (vmPFC) which was related to greater impulsivity in CCS users. Significantly
      decreased integration was found in CCS users between the vmPFC and the default
      mode network. Also, significantly enhanced functional connectivity was found
      between the vmPFC and the right insula, and the right dorsal lateral PFC.
      Negative correlation was observed between BIS total scores, scores for
      attentional impulsivity and vmPFC-inferior parietal lobe connectivity in CCS
      users. CONCLUSIONS: The findings revealed volume loss and aberrant functional
      organization in vmPFC among CCS users. In addition, the decreased vmPFC GM volume
      and attenuated functional connectivity of the vmPFC-inferior parietal lobe
      network were associated with clinical higher impulsivity trait in CCS users.

PMID- 24286969
TI  - Determining 'age at death' for forensic purposes using human bone by a laboratory
      based biomechanical analytical method.
AB  - Determination of age-at-death (AAD) is an important and frequent requirement in
      contemporary forensic science and in the reconstruction of past populations and
      societies from their remains. Its estimation is relatively straightforward and
      accurate (+/-3yr) for immature skeletons by using morphological features and
      reference tables within the context of forensic anthropology. However, after
      skeletal maturity (>35yr) estimates become inaccurate, particularly in the legal
      context. In line with the general migration of all the forensic sciences from
      reliance upon empirical criteria to those which are more evidence-based, AAD
      determination should rely more-and-more upon more quantitative methods. We
      explore here whether well-known changes in the biomechanical properties of bone
      and the properties of bone matrix, which have been seen to change with age even
      after skeletal maturity in a traceable manner, can be used to provide a reliable
      estimate of AAD. This method charts a combination of physical characteristics
      some of which are measured at a macroscopic level (wet & dry apparent density,
      porosity, organic/mineral/water fractions, collagen thermal degradation
      properties, ash content) and others at the microscopic level (Ca/P ratios,
      osteonal and matrix microhardness, image analysis of sections). This method
      produced successful age estimates on a cohort of 12 donors of age 53-85yr (7
      male, 5 female), where the age of the individual could be approximated within
      less than +/-1yr. This represents a vastly improved level of accuracy than
      currently extant age estimation techniques. It also presents: (1) a greater level
      of reliability and objectivity as the results are not dependent on the experience
      and expertise of the observer, as is so often the case in forensic skeletal age
      estimation methods; (2) it is purely laboratory-based analytical technique which
      can be carried out by someone with technical skills and not the specialised
      forensic anthropology experience; (3) it can be applied worldwide following
      stringent laboratory protocols. As such, this technique contributes significantly
      to improving age estimation and therefore identification methods for forensic and
      other purposes. 

PMID- 24286970
TI  - Heteronuclear dipolar coupling in spin-1 NQR pulsed spin locking.
AB  - We investigate theoretically and experimentally the role of broadening due to
      heteronuclear dipolar coupling in spin-1 nuclear quadrupole resonance pulsed spin
      locking. We find the experimental conditions where heteronuclear dipolar coupling
      is refocused by a standard multipulse sequence. This experimental condition
      allows us to extend our previously reported ability to measure the homonuclear
      dipolar coupling of powder samples to include substances that have heteronuclear
      coupling. These results are useful for designing substance detection algorithms,
      and for performing sample characterization. 

PMID- 24286971
TI  - The availability of glucose to CHO cells affects the intracellular lipid-linked
      oligosaccharide distribution, site occupancy and the N-glycosylation profile of a
      monoclonal antibody.
AB  - The glycosylation pattern of a chimeric heavy chain antibody (EG2) produced from
      CHO cells was affected by the glucose concentration (0-25mM) of cultures
      established at high density (>10(6)ml(-1)) over 24h. The resulting proportion of
      non-glycosylated Mab was directly correlated to the exposure time of cells to
      media depleted of glucose. Deprivation of glucose for the full 24h resulted in a
      45% non-glycosylated Mab fraction. Analysis of steady state levels of
      intracellular lipid-linked oligosaccharides (LLOs) showed that under glucose
      limitation there was a reduction in the amount of full length LLO
      (Glc3Man9GlcNac2), with a concomitant increase in the smaller mannosyl-glycans
      (Man2-5GlcNAc2). Glycan microheterogeneity was quantified by galactosylation and
      sialylation indices (GI and SI) which showed a direct correlation to the cell
      specific glucose uptake. The GI increased to 0.83 following media supplementation
      with a cocktail of uridine, manganese and galactose. This is significantly higher
      than for a fully humanized antibody (DP12) produced under the similar conditions
      or for similar antibodies reported in the literature. The high GI of the chimeric
      antibody (EG2) may be due to its low molecular weight and unusual structure.
      These findings are important in relation to the low substrate that may occur in
      fed-batch cultures for Mab production. 

PMID- 24286972
TI  - Chronic kidney disease: who is affected, who is at risk and who cares?

PMID- 24286973
TI  - Insulin resistance in chronic kidney disease: new lessons from experimental
      models.
AB  - Insulin resistance (IR) is a common feature of chronic kidney disease (CKD), but
      the underlying mechanisms still remain unclear. A growing body of evidence
      suggests that IR and its associated metabolic disorders are important
      contributors for the cardiovascular burden of these patients. In recent years,
      the modification of the intestinal flora and activation of inflammation pathways
      have been implicated in the pathogenesis of IR in obese and diabetic patients.
      All these pathways ultimately lead to lipid accumulation in ectopic sites and
      impair insulin signalling. These important discoveries have led to major advances
      in understanding the mechanisms of uraemia-induced IR. Indeed, recent studies
      show impairment of the intestinal barrier function and changes in the composition
      of the gut microbiome during CKD that can contribute to the prevailing
      inflammation, and the production and absorption of toxins generated from
      bacterial metabolism. The specific role of individual uraemic toxins in the
      pathogenesis of IR has been highlighted in rodents. Moreover, correcting some
      uraemia-associated factors by modulating the intestinal flora improves insulin
      sensitivity. This review outlines potential mechanisms by which important
      modifications of body homeostasis induced by the decline in kidney function can
      affect insulin sensitivity, and the relevance of recent advances in the field to
      provide novel therapeutic approaches to reduce IR associated cardiovascular
      mortality. 

PMID- 24286974
TI  - A clinical stratification tool for chronic kidney disease progression rate based
      on classification tree analysis.
AB  - BACKGROUND: Registry-based studies have identified risk factors for chronic
      kidney disease (CKD) and for progression to end-stage renal disease. However,
      usually, these studies do not incorporate sequential measurements of kidney
      function and provide little information on the prognosis of individual patients.
      The aim of this study is to identify which combinations of demographic and
      clinical characteristics are useful to discriminate patients with a differential
      annual decline in glomerular filtration rate (GFR). METHODS: This observational
      retrospective study includes patients enlisted in the registry of the Prevention
      of Progressive Renal Insufficiency Project of Emilia-Romagna region (Italy) from
      July 2004 to June 2010, with at least four serum creatinine measurements.
      Classification tree analysis (CTA) was used to identify subgroups of patients
      with a different annual GFR decline using demographic and laboratory data
      collected at study entry. RESULTS: The CTA procedure generated seven mutually
      exclusive groups. Among patients with proteinuria, those with a baseline
      estimated GFR (eGFR) of >33 mL/min/1.73 m(2) exhibited the fastest illness
      progression in the study population (-3.655 mL/min/1.73 m(2)), followed by
      patients with a baseline eGFR of <33 mL/min/1.73 m(2) and a baseline serum
      phosphorus of >4.3 mg/dL (-2.833 mL/min/1.73 m(2)). Among patients without
      proteinuria, those aged <67 years exhibited a significantly faster progression,
      which was even faster for the subgroup with diabetes. Among patients aged >67
      years, females had on average a stable eGFR over time, with a large variability.
      CONCLUSIONS: It is possible to rely on a few variables typically accessible in
      routine clinical practice to stratify patients with a different CKD progression
      rate. Stratification can be used to guide decisions about the follow-up schedule,
      treatments to slow progression of kidney disease, prevent its complications and
      to begin planning for dialysis and transplantation.

PMID- 24286975
TI  - A look at the upper heart chamber: the left atrium in chronic kidney disease.
AB  - Altered left ventricular (LV) mass and function are classical hallmarks of
      cardiomyopathy in chronic kidney disease (CKD). The left atrium (LA), a heart
      chamber exquisitely sensitive to volume overload and diastolic function, is an
      independent predictor of death and adverse cardiovascular (CV) events in high
      risk patients such as those with hypertension and/or with heart failure. In this
      review we focus on the relationship of LA size with LV diastolic function, and
      the association between LA enlargement and CV and renal outcomes in patients with
      CKD, including patients with end-stage renal disease. Increased LA size emerges
      as a powerful predictor of mortality and major adverse CV events in both end
      stage and early CKD, and some studies also show a close association between
      enlarged LA and renal disease progression. Secondary analyses of clinical trials
      suggest that the LA has the potential to be elected as a surrogate end point in
      CKD patients but the issue remains to be tested in specifically designed clinical
      studies. 

PMID- 24286976
TI  - Recent advances in our understanding of insulin signalling to the podocyte.
AB  - It is becoming increasingly clear that the insulin responses of a number of
      different cell types within the kidney are important in the maintenance of normal
      renal function. This review summarizes our current understanding of renal insulin
      signalling, with specific focus on the podocyte, presenting recent evidence that
      suggests these responses are altered in systemic insulin-resistant states and
      chronic kidney disease via a number of different mechanisms. 

PMID- 24286977
TI  - Low hepcidin triggers hepatic iron accumulation in patients with hepatitis C.
AB  - Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver
      disease including fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Chronic
      hepatitis C (CHC) is also a problem in patients with chronic kidney disease
      (CKD), particularly in those on haemodialysis. Excessive iron in the liver of CHC
      patients contributes to hepatic fibrosis, cirrhosis and finally HCC, while iron
      depletion is beneficial. In CHC patients without CKD, in HCV-infected
      experimental animals and in cell culture studies, serum hepcidin levels and/or
      cellular hepcidin expression are low and directly suppressed by HCV, radical
      oxygen species, growth factors and/or transcription factors. In contrast,
      antiviral therapy (e.g. with pegylated interferon-alpha combined with ribavirin)
      raises hepcidin levels and reduces iron overload in patients with CHC. Hepcidin
      directly inhibits HCV replication mediated by STAT3 activation. HCV circumvents
      hepatic innate antiviral defence by lowering hepcidin. If hepcidin is also low in
      CKD patients with CHC, iron supplementation should be avoided even in CKD
      patients with CHC treated with erythropoiesis-stimulating agents. 

PMID- 24286978
TI  - Measuring the quality of renal care: things to keep in mind when selecting and
      using quality indicators.
AB  - This educational paper discusses a variety of indicators that can be used to
      measure the quality of care in renal medicine. Based on what aspect of care they
      reflect, indicators can be grouped into four main categories: structure, process,
      surrogate outcome and outcome indicators. Each category has its own advantages
      and disadvantages, and we give some pointers on how to balance these pros and
      cons while taking into account the aim of the measurement initiative. Especially
      within initiatives that link payment or reputation to indicator measurement, this
      balancing should be done with utmost care to avoid potential, unintended
      consequences. Furthermore, we suggest consideration of (i) a causal chain-i.e.
      subsequent aspects of care connected by evidence-based links-as a starting point
      for composing a performance indicator set and (ii) adequate case-mix adjustment,
      not only of (surrogate) outcomes, but also of process indicators in order to
      obtain fair comparisons between facilities and within facilities over time. 

PMID- 24286979
TI  - Kidney Disease: Improving Global Outcomes--an update.
AB  - Kidney Disease: Improving Global Outcomes (KDIGO) was founded in 2003 to fulfill
      a need for international cooperation and consolidation in the development and
      implementation of clinical practice guidelines. KDIGO has experienced a rapid
      growth in the development of guidelines, producing three guidelines in its first
      6 years and another six in the last 3 years. In addition, it has held 12 global
      conferences on important issues in kidney disease and its treatment. A major
      effort is under way to support the dissemination and implementation of KDIGO
      guidelines through various channels, including an Implementation Task Force with
      official representatives in 86 countries. KDIGO is now under its own management
      and remains committed to the development of evidence-based guidelines. Future
      challenges include finding adequate sources of funding and building stronger
      links with other organizations involved in guideline development and
      implementation. 

PMID- 24286980
TI  - Immobilizing live Escherichia coli for AFM studies of surface dynamics.
AB  - Atomic force microscopy (AFM) is a probe-based technique that permits high
      resolution imaging of live bacterial cells. However, stably immobilizing cells to
      withstand the probe-based lateral forces remains an obstacle in AFM mediated
      studies, especially those of live, rod shaped bacteria in nutrient media.
      Consequently, AFM has been under-utilized in the research of bacterial surface
      dynamics. The aim of the current study was to immobilize a less adherent
      Escherichia coli strain in a method that both facilitates AFM imaging in nutrient
      broth and preserves overall cell viability. Immobilization reagents and buffers
      were systematically evaluated and the cell membrane integrity was monitored in
      all sample preparations. As expected, the biocompatible gelatin coated surfaces
      facilitated stable cell attachment in lower ionic strength buffers, yet poorly
      immobilized cells in higher ionic strength buffers. In comparison, poly-l-lysine
      surfaces bound cells in both low and high ionic strength buffers. The benefit of
      the poly-l-lysine binding capacity was offset by the compromised membrane
      integrity exhibited by cells on poly-l-lysine surfaces. However, the addition of
      divalent cations and glucose to the immobilization buffer was found to mitigate
      this unfavorable effect. Ultimately, immobilization of E. coli cells on poly-l
      lysine surfaces in a lower ionic strength buffer supplemented with Mg(2+) and
      Ca(2+) was determined to provide optimal cell attachment without compromising the
      overall cell viability. Cells immobilized in this method were stably imaged in
      media through multiple division cycles. Furthermore, permeability assays
      indicated that E. coli cells recover from the hypoosmotic stress caused by
      immobilization in low ionic strength buffers. Taken together, this data suggests
      that stable immobilization of viable cells on poly-l-lysine surfaces can be
      accomplished in lower ionic strength buffers that are supplemented with divalent
      cations for membrane stabilization while minimizing binding interference. The
      data also indicates that monitoring cell viability as a function of sample
      preparation is important and should be an integral part of the work flow for
      determining immobilization parameters. A method for immobilizing a less adherent
      E. coli mutant for AFM imaging in nutrient broth is presented here in addition to
      a proposed work flow for developing and optimizing immobilization strategies. 

PMID- 24286981
TI  - Global gene expression of methicillin-resistant Staphylococcus aureus USA300
      during human and mouse infection.
AB  - Little is known about the expression of methicillin-resistant Staphylococcus
      aureus (MRSA) genes during infection conditions. Here, we described the
      transcriptome of the clinical MRSA strain USA300 derived from human cutaneous
      abscesses, and compared it with USA300 bacteria derived from infected kidneys in
      a mouse model. Remarkable similarity between the transcriptomes allowed us to
      identify genes encoding multiple proteases and toxins, and iron- and peptide
      transporter molecules, which are upregulated in both infections and are likely
      important for establishment of infection. We also showed that disruption of the
      global transcriptional regulators agr and sae prevents in vivo upregulation of
      many toxins and proteases, protecting mice from lethal infection dose, and
      hinting at the role of these transcriptional regulators in the pathology of MRSA
      infection. 

PMID- 24286982
TI  - HIV antibody characterization as a method to quantify reservoir size during
      curative interventions.
AB  - Quantitative humoral profiling of recent samples from a human immunodeficiency
      virus (HIV)-infected adult who was cured following a delta32/delta32 CCR5 stem
      cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid,
      integrase, protease, and gp120, but low levels of antibodies against reverse
      transcriptase, tat, and gp41. Antibody levels to these HIV proteins persisted at
      high and stable levels in most noncontrollers, elite controllers, and
      antiretroviral-treated subjects, but a rare subset of controllers had low levels
      of antibodies against matrix, reverse transcriptase, integrase, and/or protease.
      Comprehensive HIV antibody profiles may prove useful for monitoring curative
      interventions. 

PMID- 24286983
TI  - Combination therapy with lysin CF-301 and antibiotic is superior to antibiotic
      alone for treating methicillin-resistant Staphylococcus aureus-induced murine
      bacteremia.
AB  - Lysins are bacteriophage-derived enzymes that degrade bacterial peptidoglycans.
      Lysin CF-301 is being developed to treat Staphylococcus aureus because of its
      potent, specific, and rapid bacteriolytic effects. It also demonstrates activity
      on drug-resistant strains, has a low resistance profile, eradicates biofilms, and
      acts synergistically with antibiotics. CF-301 was bacteriolytic against 250 S.
      aureus strains tested including 120 methicillin-resistant S. aureus (MRSA)
      isolates. In time-kill studies with 62 strains, CF-301 reduced S. aureus by 3
      log10 within 30 minutes compared to 6-12 hours required by antibiotics. In
      bacteremia, CF-301 increased survival by reducing blood MRSA 100-fold within 1
      hour. Combinations of CF-301 with vancomycin or daptomycin synergized in vitro
      and increased survival significantly in staphylococcal-induced bacteremia
      compared to treatment with antibiotics alone (P < .0001). Superiority of CF-301
      combinations with antibiotics was confirmed in 26 independent bacteremia studies.
      Combinations including CF-301 and antibiotics represent an attractive alternative
      to antibiotic monotherapies currently used to treat S. aureus bacteremia. 

PMID- 24286984
TI  - Taking a bite out of mosquitoes: a new drug to block transmission of malaria.

PMID- 24286985
TI  - Polypharmacy: a necessary evil.

PMID- 24286986
TI  - Lower threshold for rapid antigen detection testing in patients with sore throats
      would reduce antibiotic use.

PMID- 24286987
TI  - Authors' reply to Bjerrum and colleagues.

PMID- 24286988
TI  - Variant CJD still poses threat to public health, warn experts.

PMID- 24286989
TI  - US regulators relax restrictions on rosiglitazone.

PMID- 24286990
TI  - ToxMix 2011: International Toxicology of Mixtures Conference. A selection of
      papers. Preface.

PMID- 24286991
TI  - The German Version of the Hopkins Symptoms Checklist-25 (HSCL-25) --factorial
      structure, psychometric properties, and population-based norms.
AB  - PURPOSE: The Hopkins Symptom Checklist-25 (HSCL-25) has often been used in cross
      cultural settings and in studies focussing on asylum seekers, refugees etc. It is
      available in a number of languages. The present study investigates the
      psychometric properties of the German version of the HSCL-25 and delivers
      population-based norms. METHODS: Psychometric properties are investigated in a
      population-based representative sample of the German general population (N=2516).
      Seven different factorial models are compared using confirmatory factor analysis.
      RESULTS: Two out of the seven models show the best model fit. Because of the high
      inter-correlations of the factors of the tripartite model, the bifactor model is
      the preferable factor solution. The internal consistencies (Cronbach's alpha)
      were 0.84, 0.92, and 0.94 for the anxiety, the depression and the total score,
      respectively. The correlations of both subscales of this model with the subscales
      of the Brief-Symptom-Inventory-18 or the Patient Health Questionnaire-4 point
      out, that there is only marginal differential information of the subscales.
      CONCLUSION: Considering the third ("general") factor of the bifactor model with
      all items loading on it and the absence of differential correlations of the
      subscales with the external criteria (PHQ-4, BSI-18) the HSCL-25 seems to assess
      something like "mental distress" with a focus on symptoms of depression and
      anxiety. The population-based norms support the application of the HSCL-25 for
      individual diagnostics as well as for the comparison of specific samples with the
      general population.

PMID- 24286992
TI  - Patient safety in the obstetric and gynecologic office setting.
AB  - The modern patient safety movement began around 2000, when attention was drawn to
      error-related hospital mortality by the Institute of Medicine. Several years
      later the American College of Obstetricians and Gynecologists addressed safety
      issues in office practice, in recognition of the migration of increasingly
      complex surgical procedures to the office setting. Efforts begun in 2008 resulted
      in development of a program for safety certification of ob/gyn offices. Elements
      of the program are described, with recommendations on how they can be
      incorporated into standard office practice to reduce the chances of patient harm
      caused by errors or other adverse events. 

PMID- 24286993
TI  - Pain relief for obstetric and gynecologic ambulatory procedures.
AB  - As minor gynecologic procedures move from the operating room to the office,
      providers need to ensure that patients are comfortable and that procedures are
      performed safely. Although local anesthesia is commonly used for gynecologic
      procedures, a multimodal approach may be more effective. If necessary, sedation
      can be safely provided in an office setting with the correct tools and training.
      This article reviews evidence-based approaches to pain management for gynecologic
      procedures in the ambulatory setting. 

PMID- 24286994
TI  - First-trimester surgical abortion technique.
AB  - New data have emerged to support changes in first-trimester abortion practice in
      regard to antibiotic prophylaxis, cervical ripening, the use of manual vacuum
      aspiration, and pain management. This article addresses these new recommendations
      and reviews techniques in performing manual and electric vacuum uterine
      aspiration procedures before 14 weeks' gestation, including very early abortion
      (<7 weeks' gestation), technically difficult abortions, management of
      complications, and postabortal contraception. The information discussed also
      applies to miscarriage management.

PMID- 24286995
TI  - Hysteroscopic sterilization in the office setting.
AB  - Hysteroscopic sterilization is growing in popularity. Nearly 500,000 women have
      been sterilized using this method, and an increasing number of physicians are now
      performing this procedure in the office setting. The office setting can provide a
      cost-effective, convenient, and safe environment for hysteroscopic sterilization.
      Patients may benefit from avoiding hospital preoperative visits, excessive
      laboratory evaluation, operating room wait times, and expense associated with
      hospital care. Physicians may improve productivity through remaining in their
      office or avoiding operating room delays. This article reviews office
      hysteroscopic sterilization with the Essure microinsert system. 

PMID- 24286996
TI  - Global ablation techniques.
AB  - Global endometrial ablation techniques are a relatively new surgical technology
      for the treatment of heavy menstrual bleeding that can now be used even in an
      outpatient clinic setting. A comparison of global ablation versus earlier
      ablation technologies notes no significant differences in success rates and some
      improvement in patient satisfaction. The advantages of the newer global
      endometrial ablation systems include less operative time, improved recovery time,
      and decreased anesthetic risk. Ablation procedures performed in an outpatient
      surgical or clinic setting provide advantages both of potential cost savings for
      patients and the health care system and improved patient convenience. 

PMID- 24286997
TI  - Contraceptive procedures.
AB  - Although most women desire to control the size and spacing of their family, the
      rate of unintended pregnancy in the United States remains high, with
      approximately half of all pregnancies being unintended. Reducing unintended
      pregnancy is a national public health goal, and the increased use of long-acting
      reversible contraceptives (LARCs) (intrauterine devices and implants) can help
      meet this goal. LARCs are among the most effective forms of contraception
      available. There are few contraindications to their use, and insertion and
      removal are straightforward procedures that are well tolerated in the outpatient
      office setting. 

PMID- 24286998
TI  - Performance of a colposcopic examination, a loop electrosurgical procedure, and
      cryotherapy of the cervix.
AB  - Colposcopy is the accepted diagnostic test for evaluation of an abnormal Pap test
      to determine the location and extent of cervical intraepithelial lesions (CIN).
      Loop electrocautery excision procedure (LEEP) is the preferred procedure for
      advanced diagnosis and treatment of CIN following colposcopy. Although LEEP is
      the preferred treatment of CIN, cryotherapy is an option for treatment in some
      settings due to it's ease of performance, minimal complications, and cost
      effectiveness. This article focuses on the proper technique and use of these
      procedures to evaluate and treat cervical abnormalities. 

PMID- 24286999
TI  - Vulvar procedures: biopsy, bartholin abscess treatment, and condyloma treatment.
AB  - Several benign, premalignant, and malignant lesions may arise on the vulva, and
      multiple types of procedures may be used to diagnose and treat these conditions.
      Punch and shave biopsies may be used to diagnose most vulvar conditions, but
      lesions suspected of being melanomas may best be diagnosed with narrow-margin
      excisional biopsies. Bartholin gland cysts and abscesses may be treated with
      several different treatment modalities, the most common of which are
      fistulization and marsupialization. Genital warts may be treated with several
      medical and surgical modalities to relieve symptoms. 

PMID- 24287000
TI  - Cystoscopy and other urogynecologic procedures.
AB  - Female pelvic medicine and reconstructive surgery (FPMRS) is a rapidly expanding
      surgical specialty that focuses on the evaluation and treatment of pelvic floor
      disorders in women. Evaluation and treatment of several pelvic floor disorders
      can be accomplished with office-based procedures, yielding significant advantages
      to the patient, physician, and health system. This article describes the common
      and more useful office-based procedures for the FPMRS physician, covering 4 major
      categories: cystourethroscopy, procedures for stress urinary incontinence,
      procedures for urge urinary incontinence, and management of surgical
      complications. 

PMID- 24287001
TI  - Reimbursement for office-based gynecologic procedures.
AB  - Reimbursement for office-based gynecologic procedures varies with the contractual
      obligations that the physician has with the payers involved with the care of the
      particular patient. The payers may be patients without health insurance coverage
      (self-pay) or patients with third-party health insurance coverage, such as an
      employer-based commercial insurance carrier or a government program (eg, Medicare
      [federal] or Medicaid [state based]). This article discusses the reimbursement
      for office-based gynecologic procedures by third-party payers. 

PMID- 24287002
TI  - Obstetric and gynecologic procedures in the office.

PMID- 24287003
TI  - Procedures in the office setting.

PMID- 24287004
TI  - Pharmacological characterization of the vascular effects of aryl isothiocyanates:
      is hydrogen sulfide the real player?
AB  - Hydrogen sulfide (H2S) is an endogenous gasotransmitter, which mediates important
      physiological effects in the cardiovascular system. Accordingly, an impaired
      production of endogenous H2S contributes to the pathogenesis of important
      cardiovascular disorders, such as hypertension. Therefore, exogenous compounds,
      acting as H2S-releasing agents, are viewed as promising pharmacotherapeutic
      agents for cardiovascular diseases. Thus, this paper aimed at evaluating the H2S
      releasing properties of some aryl isothiocyanate derivatives and their vascular
      effects. The release of H2S was determined by amperometry, spectrophotometry and
      gas/mass chromatography. Moreover, the vascular activity of selected
      isothiocyanates were tested in rat conductance (aorta) and coronary arteries.
      Since H2S has been recently reported to act as an activator of vascular Kv7
      potassium channels, the possible membrane hyperpolarizing effects of
      isothiocyanates were tested on human vascular smooth muscle (VSM) cells by
      spectrofluorescent dyes. Among the tested compounds, phenyl isothiocyanate
      (PhNCS) and 4-carboxyphenyl isothiocyanate (PhNCS-COOH) exhibited slow-H2S
      release, triggered by organic thiols such as L-cysteine. These compounds were
      endowed with vasorelaxing effects on conductance and coronary arteries. Moreover,
      these two isothiocyanates caused membrane hyperpolarization of VSM cells. The
      vascular effects of isothiocyanates were strongly abolished by the selective Kv7
      blocker XE991. In conclusion, the isothiocyanate function can be viewed as a
      suitable slow H2S-releasing moiety, endowed with vasorelaxing and hypotensive
      effects, typical of this gasotransmitter. Thus, such a chemical moiety can be
      employed for the development of novel chemical tools for basic studies and
      promising cardiovascular drugs.

PMID- 24287005
TI  - [Moth-eaten alopecia of sudden onset and cutaneous lesions on the soles of the
      feet].

PMID- 24287006
TI  - Life-long endurance exercise in humans: circulating levels of inflammatory
      markers and leg muscle size.
AB  - Human aging is associated with a loss of skeletal muscle and an increase in
      circulating inflammatory markers. It is unknown whether endurance training (Tr)
      can prevent these changes. Therefore we studied 15 old trained (O-Tr) healthy
      males and, for comparison, 12 old untrained (O-Un), 10 Young-Tr (Y-Tr) and 12
      Young-Un (Y-Un). Quadriceps size, VO2 peak, CRP, IL-6, TNF-alpha and its
      receptors, suPAR, lipid profile, leucocytes and glucose homeostasis were
      measured. Tr was associated with an improved insulin profile (p<0.05), and lower
      leucocyte (p<0.05) and triglyceride levels (p<0.05), independent of age. Aging
      was associated with poorer glucose control (p<0.05), independent of training. The
      age-related changes in waist circumference, VO2 peak, cholesterol, LDL, leg
      muscle size, CRP and IL-6 were counteracted by physical activity (p<0.05). A
      significant increase in suPAR with age was observed (p<0.05). Most importantly,
      life-long endurance exercise was associated with a lower level of the
      inflammatory markers CRP and IL-6 (p<0.05), and with a greater thigh muscle area
      (p<0.05), compared to age-matched untrained counterparts. These findings in a
      limited group of individuals suggest that regular physical endurance activity may
      play a role in reducing some markers of systemic inflammation, even within the
      normal range, and in maintaining muscle mass with aging. 

PMID- 24287007
TI  - The systolic blood pressure difference between arms and cardiovascular disease in
      the Framingham Heart Study.
AB  - BACKGROUND: An increased interarm systolic blood pressure difference is an easily
      determined physical examination finding. The relationship between interarm
      systolic blood pressure difference and risk of future cardiovascular disease is
      uncertain. We described the prevalence and risk factor correlates of interarm
      systolic blood pressure difference in the Framingham Heart Study (FHS) original
      and offspring cohorts and examined the association between interarm systolic
      blood pressure difference and incident cardiovascular disease and all-cause
      mortality. METHODS: An increased interarm systolic blood pressure difference was
      defined as >= 10 mm Hg using the average of initial and repeat blood pressure
      measurements obtained in both arms. Participants were followed through 2010 for
      incident cardiovascular disease events. Multivariable Cox proportional hazards
      regression analyses were performed to investigate the effect of interarm systolic
      blood pressure difference on incident cardiovascular disease. RESULTS: We
      examined 3390 (56.3% female) participants aged 40 years and older, free of
      cardiovascular disease at baseline, mean age of 61.1 years, who attended a FHS
      examination between 1991 and 1994 (original cohort) and from 1995 to 1998
      (offspring cohort). The mean absolute interarm systolic blood pressure difference
      was 4.6 mm Hg (range 0-78). Increased interarm systolic blood pressure difference
      was present in 317 (9.4%) participants. The median follow-up time was 13.3 years,
      during which time 598 participants (17.6%) experienced a first cardiovascular
      event, including 83 (26.2%) participants with interarm systolic blood pressure
      difference >= 10 mm Hg. Compared with those with normal interarm systolic blood
      pressure difference, participants with an elevated interarm systolic blood
      pressure difference were older (63.0 years vs 60.9 years), had a greater
      prevalence of diabetes mellitus (13.3% vs 7.5%,), higher systolic blood pressure
      (136.3 mm Hg vs 129.3 mm Hg), and a higher total cholesterol level (212.1 mg/dL
      vs 206.5 mg/dL). Interarm systolic blood pressure difference was associated with
      a significantly increased hazard of incident cardiovascular events in the
      multivariable adjusted model (hazard ratio 1.38; 95% CI, 1.09-1.75). For each 1
      SD-unit increase in absolute interarm systolic blood pressure difference, the
      hazard ratio for incident cardiovascular events was 1.07 (95% CI, 1.00-1.14) in
      the fully adjusted model. There was no such association with mortality (hazard
      ratio 1.02; 95% CI 0.76-1.38). CONCLUSIONS: In this community-based cohort, an
      interarm systolic blood pressure difference is common and associated with a
      significant increased risk for future cardiovascular events, even when the
      absolute difference in arm systolic blood pressure is modest. These findings
      support research to expand clinical use of this simple measurement.

PMID- 24287008
TI  - New electrocardiographic criteria to differentiate acute pericarditis and
      myocardial infarction.
AB  - OBJECTIVE: Transmural myocardial ischemia induces changes in QRS complex and QT
      interval duration but, theoretically, these changes might not occur in acute
      pericarditis provided that the injury is not transmural. This study aims to
      assess whether QRS and QT duration permit distinguishing acute pericarditis and
      acute transmural myocardial ischemia. METHODS: Clinical records and 12-lead
      electrocardiogram (ECG) at *2 magnification were analyzed in 79 patients with
      acute pericarditis and in 71 with acute ST-segment elevation myocardial
      infarction (STEMI). RESULTS: ECG leads with maximal ST-segment elevation showed
      longer QRS complex and shorter QT interval than leads with isoelectric ST segment
      in patients with STEMI (QRS: 85.9 +/- 13.6 ms vs 81.3 +/- 10.4 ms, P = .01; QT:
      364.4 +/- 38.6 vs 370.9 +/- 37.0 ms, P = .04), but not in patients with
      pericarditis (QRS: 81.5 +/- 12.5 ms vs 81.0 +/- 7.9 ms, P = .69; QT: 347.9 +/-
      32.4 vs 347.3 +/- 35.1 ms, P = .83). QT interval dispersion among the 12-ECG
      leads was greater in STEMI than in patients with pericarditis (69.8 +/- 20.8 ms
      vs 50.6 +/- 20.2 ms, P <.001). The diagnostic yield of classical ECG criteria (PR
      deviation and J point level in lead aVR and the number of leads with ST-segment
      elevation, ST-segment depression, and PR-segment depression) increased
      significantly (P = .012) when the QRS and QT changes were added to the diagnostic
      algorithm. CONCLUSIONS: Patients with acute STEMI, but not those with acute
      pericarditis, show prolongation of QRS complex and shortening of QT interval in
      ECG leads with ST-segment elevation. These new findings may improve the
      differential diagnostic yield of the classical ECG criteria.

PMID- 24287009
TI  - The impacts of neutralized acid mine drainage contaminated water on the
      expression of selected endocrine-linked genes in juvenile Mozambique tilapia
      Oreochromis mossambicus exposed in vivo.
AB  - Acid mine drainage (AMD) is a global environmental concern due to detrimental
      impacts on river ecosystems. Little is however known regarding the biological
      impacts of neutralized AMD on aquatic vertebrates despite excessive discharge
      into watercourses. The aim of this investigation was to evaluate the endocrine
      modulatory potential of neutralized AMD, using molecular biomarkers in the
      teleost fish Oreochromis mossambicus in exposure studies. Surface water was
      collected from six locations downstream of a high density sludge (HDS) AMD
      treatment plant and a reference site unimpacted by AMD. The concentrations of 28
      elements, including 22 metals, were quantified in the exposure water in order to
      identify potential links to altered gene expression. Relatively high
      concentrations of manganese (~ 10mg/l), nickel (~ 0.1mg/l) and cobalt (~ 0.03
      mg/l) were detected downstream of the HDS plant. The expression of thyroid
      receptor-alpha (tralpha), trbeta, androgen receptor-1 (ar1), ar2, glucocorticoid
      receptor-1 (gr1), gr2, mineralocorticoid receptor (mr) and aromatase (cyp19a1b)
      was quantified in juvenile fish after 48 h exposure. Slight but significant
      changes were observed in the expression of gr1 and mr in fish exposed to water
      collected directly downstream of the HDS plant, consisting of approximately 95
      percent neutralized AMD. The most pronounced alterations in gene expression (i.e.
      tralpha, trbeta, gr1, gr2, ar1 and mr) was associated with water collected
      further downstream at a location with no other apparent contamination vectors
      apart from the neutralized AMD. The altered gene expression associated with the
      "downstream" locality coincided with higher concentrations of certain metals
      relative to the locality adjacent to the HDS plant which may indicate a causative
      link. The current study provides evidence of endocrine disruptive activity
      associated with neutralized AMD contamination in regard to alterations in the
      expression of key genes linked to the thyroid, interrenal and gonadal endocrine
      axes of a teleost fish species.

PMID- 24287010
TI  - Ecotoxicity of chemically stabilised metal(loid)s in shooting range soils.
AB  - Five chemical amendments (soft rock phosphate, lime, commercial phosphate
      amendment, red mud and magnesium oxide) were applied across four different
      shooting range soils to chemically stabilise metal(loid)s in the soils. Soils
      were contaminated with Pb between 2330 and 12,167 mg/kg, Sb from 7.4 to 325 mg/kg
      and soil pH ranged from 5.43 to 9.29. Amendments were tested for their ability to
      reduce the bioavailability of Pb, Sb, Zn, Ni, Cu and As in the soils to soil
      organisms after one year of aging, by measuring a series of ecotoxicological
      endpoints for earthworms and plants and soil microbial activity. Growth-based
      endpoints for earthworms and plants were not significantly affected by amendment
      addition, except in the most contaminated soil. Per cent survival and weight-loss
      reduction of earthworms was enhanced by amendment addition in only the most
      contaminated soil. Plant biomass and root elongation was not significantly
      affected by amendment addition (p=<0.05). Red mud and magnesium oxide appeared
      toxic to plants and earthworms, probably due to highly alkaline pH (9-12). Lead
      in soil organisms was relatively low despite the high concentrations of Pb in the
      soils, suggesting low bioavailability of Pb. Uptake of Pb by earthworms was
      reduced by between 40 and 96 per cent by amendments, but not across all soils.
      Amendments reduced Sb in earthworms in Townsville soil by up to 92 per cent. For
      lettuce the average uptake of Pb was reduced by 40 to 70 per cent with amendment
      addition in Townsville, Darwin and Perth soil. The effect of amendments on the
      uptake of Sb, Zn, Ni, Cu and As was variable between soils and amendments.
      Microbial activity was increased by greater than 50 per cent with amendments
      addition, with soft rock phosphate and lime being the most effective in Murray
      Bridge and TV soils and commercial phosphate and MgO being the most effective in
      Darwin and Perth soils.

PMID- 24287011
TI  - Lead from hunting activities and its potential environmental threat to wildlife
      in a protected wetland in Yucatan, Mexico.
AB  - This study provides insights into the status of lead in the protected wetland of
      El Palmar, located on the northwestern littoral of the Yucatan Peninsula. This
      reserve is ecologically and economically important because it provides feeding
      and breeding habitats for many species, as well as being an ecotourism
      destination (especially for bird watching). Although it is a protected area, duck
      species are heavily hunted within the reserve during the winter. As a result,
      animals feeding or living in sediments could be exposed to anthropogenic lead.
      Total lead and its geochemical fractionated forms were measured in sediment cores
      from six selected sites in "El Palmar" wetland, during pre- and post-hunting
      seasons, to approximate the potential environmental threat (especially for
      benthonic living/feeding organisms). Anthropogenic lead concentrations detected
      in soil cores ranged from below the minimum infaunal community effect level
      (30.24 MUg g(-1)) during the pre-hunting season, to bordering the probable
      infaunal community effect level (112.18 MUg g(-1)) during the post-hunting
      season, according to SquiiRTs NOAA guidelines. Yet, these results were lower than
      expected based on the intensity of hunting. Consequently, this article explores
      the possibility that the lower than expected lead concentration in sediments
      results from (1) degradation of shot and transformation to soluble or particulate
      forms; or (2) ingestion of lead shot by benthic and other lacustrine species
      living in the protected area. Geochemical fractionation of lead demonstrated that
      in the top 6 cm of the soil column at heavily active hunting sites (EP5 and EP6),
      lead was associated with the lithogenic fraction (average 45 percent) and with
      the organic fraction (average 20 percent). Bioavailable lead (sum of lead
      adsorbed to the carbonates, Fe/Mn oxyhydroxides and organic fractions) in
      sediments was lower than 50 percent for the heavily active hunting areas and
      higher for the rest of the sites. Multivariate analysis showed that the
      environmental chemistry, the physicochemical characteristics of the water, and
      the geochemical qualities of the sediments do not favor the release of lead into
      the water column. Thus, the direct consumption of lead shot by organisms feeding
      in sea grass or in the top 10 cm of sediment is perhaps the major process
      preventing lead from being deposited in sediments, and, as such, these species
      (e.g., flamingos and/or ducks) could be threatened by anthropogenic lead
      pollution.

PMID- 24287012
TI  - Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to
      negative symptoms of schizophrenia: a translational link to humans.
AB  - Negative symptoms of schizophrenia remain an unmet clinical need as they are
      common, persistent, respond poorly to existing treatments and lead to disability.
      Blunted affect, alogia, asociality, anhedonia and avolition are regarded as key
      negative symptoms despite DSM-IV-TR specifying a more limited range. The key to
      development of improved therapies is improved animal models that mimic the human
      condition in terms of behaviour and pathology and that predict efficacy of novel
      treatments in patients. Accumulating evidence shows that NMDA receptor (NMDAR)
      antagonists mimic cognitive deficits of relevance to schizophrenia in animals,
      along with associated pathological changes. This review examines evidence for the
      ability of NMDAR antagonists to mimic anhedonia and asociality, two negative
      symptoms of schizophrenia, in animals. The use of various species, paradigms and
      treatment regimens are reviewed. We conclude that sub-chronic treatment with
      NMDAR antagonists, typically PCP, induces social withdrawal in animals but not
      anhedonia. NMDAR antagonists have further effects in paradigms such as
      motivational salience that may be useful for mimicking other aspects of negative
      symptoms but these require further development. Sub-chronic treatment regimens of
      NMDAR antagonists also have some neurobiological effects of relevance to negative
      symptoms. It is our view that a sub-chronic treatment regime with NMDAR
      antagonists, particularly PCP, with animals tested following a wash-out period
      and in a battery of tests to assess certain behaviours of relevance to negative
      symptoms and social withdrawal (the animal equivalent of asociality) is valuable.
      This will enhance our understanding of the psycho and neuropathology of specific
      negative symptom domains and allow early detection of novel pharmacological
      targets. 

PMID- 24287013
TI  - Sibling influence on mexican-origin adolescents' deviant and sexual risk
      behaviors: the role of sibling modeling.
AB  - PURPOSE: A growing body of research indicates that siblings uniquely influence
      each other's health risk behaviors during adolescence and young adulthood.
      Mechanisms underlying these associations, however, are largely unknown because
      they are rarely tested directly. The present study addressed this gap by
      examining the role of sibling modeling in explaining changes in Mexican-origin
      youths' deviant and sexual risk behaviors over time. METHODS: The sample included
      380 Mexican-origin siblings (older sibling age: M = 21.18, SD = 1.59; younger
      sibling age: M = 18.19, SD = .46) from (N = 190) families. Participants provided
      self-reports of their sibling relationship qualities, including modeling, as well
      as their engagement in deviant and sexual risk-taking behaviors in two home
      interviews across a 2-year span. RESULTS: A series of residualized regression
      models revealed that younger siblings' perceptions of modeling moderated the
      links between older siblings' deviant and sexual risk behaviors and younger
      siblings' subsequent behaviors in those same domains. Specifically, high levels
      of modeling predicted stronger associations between older siblings' earlier and
      younger siblings' later risk behaviors controlling for younger siblings' earlier
      behaviors as well as variables that have been used as proxies for social learning
      in previous research. CONCLUSIONS: Social learning mechanisms, especially
      modeling, are salient processes through which older siblings transmit norms and
      expectations regarding participation in health risk behaviors. Future research
      should continue to explore the ways in which siblings influence each other
      because such processes are emerging targets for intervention and prevention.

PMID- 24287014
TI  - Complex health needs in the youth justice system: a survey of community-based and
      custodial offenders.
AB  - PURPOSE: Estimate the prevalence and annual frequency of health risk indicators
      in young people serving community-based orders (CBOs) and custodial orders in the
      state of Victoria, Australia. METHODS: Cross-sectional survey of 242 young people
      serving CBOs and 273 serving custodial orders in Victoria in 2002-2003. Validated
      measures included the Composite International Diagnostic Interview for substance
      dependence, Short Mood and Feelings Questionnaire for depression, and Psychosis
      Screening Questionnaire for psychosis symptoms. Prevalence estimates were
      adjusted for sampling bias and age- and sex-adjusted for between-group
      comparisons. Prevalence estimates were applied to 2010-2011 Victorian youth
      justice data to estimate annual frequencies at the state level. RESULTS: The
      prevalence of substance dependence, poor mental health, and risky sexual behavior
      was high in both groups. Age- and sex-adjusted prevalence estimates were
      generally higher among those serving custodial orders; however, extrapolating
      prevalence estimates to statewide youth justice data generally resulted in higher
      estimated annual frequencies among CBOs. For example, the estimated prevalence of
      any substance dependence was 66% (95% confidence interval [CI], 60-72) in those
      serving custodial orders and 34% (95% CI, 26-42) in CBOs, but the estimated
      frequency of substance dependence in CBOs in 2010-2011 was 970 (95% CI, 750
      1,180), compared with 490 (95% CI, 450-530) in those serving a custodial order.
      CONCLUSIONS: There is a compelling case for scaling up health services for young
      offenders in custody and in the community, and for routinely monitoring the
      health of young offenders serving custodial and community orders.

PMID- 24287016
TI  - [Gemella endocarditis: an aggressive entity].
AB  - The authors present a rare case of subacute endocarditis caused by Gemella
      morbillorum. A 72-year-old man, with a history of hypertension, aortic valve
      disease and upper and lower endoscopy six months previously, was admitted due to
      fever and abdominal pain. He also complained of long-standing dyspnea on exertion
      and petechiae on his lower limbs. Imaging scans showed a consolidation in the
      lower left lung field, a splenic infarct and a left subphrenic abscess.
      Transthoracic echocardiogram findings were highly suggestive of endocarditis
      affecting three valves, with destruction of the mitral valve anterior leaflet. G.
      morbillorum was identified in three blood cultures and was considered the
      etiologic pathogen. Due to the patient's worsening condition, he underwent
      cardiac surgery, aiming to control the infection and to resolve the associated
      mechanical complications. This case highlights the need for a complete and
      thorough history to arrive at likely diagnostic hypotheses that, together with
      complementary exams, will lead to correct diagnosis and the prompt institution of
      appropriate therapy. 

PMID- 24287015
TI  - What parents and adolescent boys want in school vaccination programs in the
      United States.
AB  - PURPOSE: Schools are increasingly a part of vaccine provision, because of laws
      mandating provision of information by schools about vaccination, school entry
      requirements, and mass vaccination campaigns. We examined preferences for
      programmatic aspects of voluntary school mass vaccination programs (i.e.,
      "vaccination days"). METHODS: We analyzed data from a national sample of United
      States parents of adolescent males ages 11-19 years (n = 308) and their sons (n =
      216), who completed an online survey in November 2011. RESULTS: Sons believed
      that adolescents should be able to get vaccinated without parental consent at a
      younger age than parents did (p < .001) and were more willing to participate in
      vaccination days without a parent present (p = .04). Parents perceived school
      vaccination days to be a more convenient way to get their sons recommended
      vaccines if they were younger parents, had older adolescent sons, supported laws
      letting schools share vaccination records with health care providers, or had sons
      who were previously immunized at school (all p < .05). Parents of older sons were
      less likely to want their sons' vaccination records sent home (odds ratio [OR] =
      .47; 95% confidence interval [CI], .29-.77) or to their sons' physicians (OR =
      .61; 95% CI, .37-.98) compared with parents of younger sons, but more likely to
      prefer their sons' records be entered in an immunization registry (OR = 1.66; 95%
      CI, 1.05-2.63). CONCLUSIONS: Sons' age had an important role in support for
      vaccination days and preferences for sharing vaccination information with health
      care professionals. Parents and sons had similar beliefs about vaccination in
      schools, but the sons' responses suggested an interest in greater autonomy.

PMID- 24287017
TI  - Effective radiation dose of three diagnostic tests in cardiology: single photon
      emission computed tomography, invasive coronary angiography and cardiac computed
      tomography angiography.
AB  - INTRODUCTION: Diagnostic tests that use ionizing radiation play a central role in
      cardiology and their use has grown in recent years, leading to increasing
      concerns about their potential stochastic effects. The aims of this study were to
      compare the radiation dose of three diagnostic tests: single photon emission
      computed tomography (SPECT), invasive coronary angiography (ICA) and cardiac
      computed tomography (cardiac CT) and their evolution over time, and to assess the
      influence of body mass index on radiation dose. METHODS: We assessed consecutive
      patients included in three prospective registries (SPECT, ICA and cardiac CT)
      over a period of two years. Radiation dose was converted to mSv and compared
      between the three registries. Differences over time were evaluated by comparing
      the first with the fourth semester. RESULTS: A total of 6196 exams were
      evaluated: 35% SPECT, 53% ICA and 22% cardiac CT. Mean radiation dose was 10.7+/
      1.2 mSv for SPECT, 8.1+/-6.4 mSv for ICA, and 5.4+/-3.8 mSv for cardiac CT
      (p<0.001 for all). With regard to the radiation dose over time, there was a very
      small reduction in SPECT (10.7 to 10.5 mSv, p=0.004), a significant increase
      (25%) in ICA (7.0 to 8.8 mSv; p<0.001), and a significant reduction (29%) in
      cardiac CT (6.5 to 4.6 mSv, p<0.001). Obesity was associated with a significantly
      higher radiation dose in all three exams. CONCLUSIONS: Cardiac CT had a lower
      mean effective radiation dose than invasive coronary angiography, which in turn
      had a lower mean effective dose than SPECT. There was a significant increase in
      radiation doses in the ICA registry and a significant decrease in the cardiac CT
      registry over time.

PMID- 24287018
TI  - Coexistence of dynamic mitral regurgitation and dynamic left ventricular
      dyssynchrony in a patient with repeated episodes of acute pulmonary edema:
      improvement with cardiac resynchronization therapy.
AB  - A 69-year-old woman with idiopathic dilated cardiomyopathy and chronic heart
      failure experienced repeated hospital admissions for acute pulmonary edema with
      no recognizable precipitating factor. Worsening mitral regurgitation was
      triggered by exercise echocardiography and significant intraventricular
      dyssynchrony was elicited by low-dose dobutamine stress echocardiography. After
      cardiac resynchronization therapy she remained free of hospitalizations for 12
      months. This case highlights the dynamic nature of both functional mitral
      regurgitation and left ventricular dyssynchrony and illustrates how in some
      patients stress echocardiography can help to clarify clinical scenarios and help
      with the challenging task of selecting patients who will benefit from cardiac
      resynchronization therapy. 

PMID- 24287019
TI  - [Prevalence of subclinical atherosclerosis and cardiovascular risk
      reclassification by measure of carotid intima-media thickness in ambulatory
      hypertensive patients].
AB  - INTRODUCTION AND OBJECTIVES: Although carotid intima-media thickness (CIMT) is
      considered a surrogate marker of subclinical atherosclerosis, with known value in
      risk stratification, its routine use in hypertensive patients is not recommended.
      The aim of this study was to determine the prevalence of subclinical
      atherosclerosis through measurement of CIMT and its impact on reclassification of
      risk in hypertensive patients. METHODS: This was a cross-sectional study of 94
      middle-aged (56.99+/-11.89 years) hypertensive outpatients without overt
      cardiovascular disease, 68.1% female. All participants underwent clinical
      examination, biochemical tests, echocardiogram and measurement of CIMT by high
      resolution ultrasound. RESULTS: Although the majority of patients were stratified
      as low (63.5%) or intermediate risk (23%) according to their Framingham score, a
      high prevalence (75.3%) of increased CIMT was observed in the overall sample,
      including in the low (61%) and intermediate risk groups (93.8%). CIMT measurement
      resulted in risk reclassification of 70.31% of the patients, 61% of those at low
      risk being reclassified as intermediate risk and 93.8% of those at intermediate
      risk being reclassified as high risk. CONCLUSION: In these hypertensive
      outpatients, predominantly middle-aged and female, CIMT measurement revealed a
      high prevalence of subclinical atherosclerosis and resulted in risk
      reclassification in the majority of cases.

PMID- 24287020
TI  - [Follow-up of implantable cardioverter-defibrillators: face-to-face or remote?].

PMID- 24287021
TI  - Cardiac magnetic resonance imaging: a non-invasive tool for the diagnosis of
      eosinophilic myocarditis.

PMID- 24287022
TI  - [Position statement on bioresorbable vascular scaffolds in Portugal].
AB  - BACKGROUND: Bioresorbable vascular scaffolds (BVS) were recently approved for
      percutaneous coronary intervention in Europe. The aim of this position statement
      is to review the information and studies on available BVS, to stimulate
      discussion on their use and to propose guidelines for this treatment option in
      Portugal. METHODS AND RESULTS: A working group was set up to reach a consensus
      based on current evidence, discussion of clinical case models and individual
      experience. The evidence suggests that currently available BVS can produce
      physiological and clinical improvements in selected patients. There are
      encouraging data on their durability and long-term safety. Initial indications
      were grouped into three categories: (a) consensual and appropriate - young
      patients, diabetic patients, left anterior descending artery, long lesions,
      diffuse disease, and hybrid strategy; (b) less consensual but possible - small
      collateral branches, stabilized acute coronary syndromes; and (c) inappropriate -
      left main disease, tortuosity, severe calcification. CONCLUSION: BVS are a viable
      treatment option based on the encouraging evidence of their applicability and
      physiological and clinical results. They should be used in appropriate
      indications and will require technical adaptations. Outcome monitoring and
      evaluation is essential to avoid inappropriate use. It is recommended that
      medical societies produce clinical guidelines based on high-quality registries as
      soon as possible.

PMID- 24287023
TI  - Percutaneous coronary intervention of unprotected left main disease: five-year
      outcome of a single-center registry.
AB  - INTRODUCTION AND AIMS: Percutaneous coronary intervention (PCI) is increasingly
      used as a treatment option for unprotected left main coronary artery (ULMCA)
      lesions. We aimed to evaluate the long-term outcome of patients undergoing ULMCA
      PCI. METHODS AND RESULTS: We retrospectively analyzed 95 consecutive patients
      (median EuroSCORE I 2.9 [IQR 1.4;6.1]) who underwent ULMCA PCI between 1999 and
      2006, included in a single-center prospective registry. The primary outcome was
      major adverse cardiovascular events (MACE) defined as all-cause death, myocardial
      infarction (MI) and target lesion revascularization (TLR) at five years. Forty
      patients (42.1%) were treated in the setting of acute coronary syndrome and 81
      patients (85%) had at least one additional significant lesion (SYNTAX score
      24.2+/-11.8). Single ULMCA PCI was performed in 33% (81.1% with drug-eluting
      stents) and complete functional revascularization was achieved in 79% of the
      patients. During the observation period, 20 patients died (21.1%), 6 (6.3%) had
      MI and 11 (11.6%) had TLR (total combined MACE 28.4%). Independent predictors of
      MACE were previous MI (HR 2.9 95% CI 1.23-6.92; p=0.015), hypertension (HR 5.7
      95% CI 1.86-17.47; p=0.002) and the EuroSCORE I (HR 1.1 95% CI 1.03-1.12;
      p=0.001). Drug-eluting stent implantation was associated with a significantly
      lower MACE rate, even after propensity score adjustment (AUC=0.84; HR [corrected]
      0.1; 95% CI 0.04-0.26; p<0.001). CONCLUSIONS: Unprotected left main percutaneous
      coronary intervention, particularly using drug-eluting stents, can be considered
      a valid alternative to coronary artery bypass grafting, especially in high-risk
      surgical patients and with favorable anatomic features.

PMID- 24287024
TI  - [Usefulness of intracoronary imaging techniques in the percutaneous treatment of
      in-stent restenosis].
AB  - We report a case of very late bare-metal stent restenosis, in which assessment by
      two intracoronary imaging techniques (intravascular ultrasound and optical
      coherence tomography) revealed the underlying mechanism (neoatherosclerosis) and
      facilitated percutaneous treatment (direct bare-metal stent-in-stent). We also
      take the opportunity to briefly describe the advantages and limitations of both
      techniques in this pathology. 

PMID- 24287025
TI  - Effect of zinc chelate and valnemulin for the treatment of swine dysentery in an
      experimental challenge study.
AB  - The aim of study was to determine the influence of zinc chelate, valnemulin and
      it's combination on Brachyspira hyodysenteriae shedding and morphological changes
      of colonic mucosa in an experimental model of swine dysentery (SD). The study was
      performed on pigs coming from a dysentery-free herd. Animals were inoculated by
      B. hyodysenteriae strain B204. When the clinical signs of SD and B.
      hyodysenteriae shedding developed, the pigs were divided into four treatment
      groups. The first group was treated with zinc chelate (250 ml/1000 L in water),
      second group was given valnemulin in feed at 75 ppm; the third group was given a
      combination of both and the fourth group was control. The results demonstrated
      therapeutic effect of valnemulin in pigs with serious SD and did not show
      therapeutic effect of chelated zinc.

PMID- 24287026
TI  - Castleman's disease and primary effusion lymphoma in a HIV-positive patient.
AB  - We present a case of primary effusion lymphoma (PEL) occurring simultaneously
      with Castleman's disease in the same patient. Castleman's disease is distinct
      from PEL, although both are associated with HHV-8. Other cases have debated
      whether the coexistence of PEL and Castleman's disease is a recurrence of an
      original PEL tumour in an extracavitary site, or a secondary HHV-8-associated
      lymphoma distinct from primary PEL. Our case, along with those described
      previously, show that co-occurrence of PEL and Castleman's disease is possible
      and plausible. PEL needs to be included in the differential diagnosis in any HIV
      positive patient who presents with a pleural effusion, and diagnosis requires
      only a simple thoracentesis and appropriate immunohistochemistry. 

PMID- 24287027
TI  - Avascular necrosis in a HIV patient receiving ritonavir and inhaled fluticasone.
AB  - We report a case of severe bilateral knee avascular necrosis in a HIV-positive
      man receiving ritonavir and inhaled fluticasone. This case highlights the need
      for a thorough medication history in patients on ritonavir-based antiretroviral
      therapy, especially where multiple prescribers are involved in the patient's
      care. 

PMID- 24287028
TI  - Correlates of shared methamphetamine injection among methamphetamine-injecting
      treatment seekers: the first report from Iran.
AB  - Shared methamphetamine injection is an emerging route of drug use among Iranian
      methamphetamine injectors. It is a primary vector for blood-borne infections. The
      aim of the current study is to determine the prevalence and correlates of shared
      methamphetamine injection in a sample of Iranian methamphetamine injecting
      treatment seekers in the south of Tehran. We surveyed male and female
      methamphetamine injectors at three drop-in centres and 18 drug-use community
      treatment programmes. Participants reported socio-demographic characteristics,
      drug use, high-risk behaviours, current status of viral infections and service
      use for drug treatment. Bivariate and multivariate logistic regression models
      were used to test associations between participants' characteristics and shared
      methamphetamine injection. Overall, 209 clients were recruited; 90.9% were male;
      52.6% reported current methamphetamine injection without any shared injection
      behaviour and 47.4% reported current shared methamphetamine injection. Shared
      methamphetamine injection was found to be primarily associated with living with
      sex partners (AOR 1.25, 95% CI 1.13-1.98), reporting >=3 years of dependence on
      methamphetamine injection (AOR 1.61, 95% CI 1.27-2.12), injection with pre-filled
      syringes in the past 12 months (AOR 1.96, 95% CI 1.47-2.42), homosexual sex
      without condom use in the past 12 months (AOR 1.85, 95% CI 1.21-2.25), the
      paucity of NA group participation in the past 12 months (AOR 0.67, 95% CI 0.41
      0.99), the paucity of attending psychotherapeutic sessions in the past 12 months
      (AOR 0.44, 95% CI 0.28-0.96) and positive hepatitis C status (AOR 1.98, 95% CI
      1.67-2.83). Deeper exploration of the relationship between shared methamphetamine
      injection and sexual risk among Iranian methamphetamine injectors would benefit
      HIV/sexually transmitted infection prevention efforts. In addition, existing
      psychosocial interventions for methamphetamine-injecting population may need to
      be adapted to better meet the risks of shared methamphetamine injectors. 

PMID- 24287029
TI  - Unmet health care needs of older people: prevalence and predictors in a French
      cross-sectional survey.
AB  - BACKGROUND: Unmet health care needs are associated with negative health outcomes,
      yet there is a paucity of data on this problem among older people. OBJECTIVE: To
      identify unmet health care needs and associated factors among older people in
      France. METHODS: This is a cross-sectional population study of people aged 70
      years or older in which 2350 respondents were interviewed in 2008-10. During a
      standardized interview, a nurse examined health problems, functional abilities
      and use of health care resources. Unmet health care needs were defined as
      situations in which a participant needed health care and did not receive it.
      RESULTS: The mean age was 83.2 +/- 7.4 years. Almost all participants reporting a
      chronic disease (98.6%) had consulted a physician in the previous 6 months. Unmet
      health care needs were found in 23.0% of the sample and mainly consisted of lack
      of dental care (prevalence of 17.7%), followed by lack of management of visual or
      hearing impairments (prevalence of 4.4% and 3.1%, respectively). Age was the main
      factor associated with unmet health care needs [compared with people aged 70-79:
      odds ratio80-89 years = 2.26 (1.70-3.03), odds ratio90 years and over = 3.85
      (2.71-5.45)]. Other associated factors were regular smoking, homebound status,
      poor socioeconomic conditions, depression, limitations in instrumental activities
      of daily living and low medical density. CONCLUSION: Unmet health care needs
      affect almost one-quarter of older people in France. Efforts should be made to
      improve oral health and develop home care, especially for the oldest-olds.

PMID- 24287030
TI  - Sweden SimSmoke: the effect of tobacco control policies on smoking and snus
      prevalence and attributable deaths.
AB  - BACKGROUND: This study examines the effect of past tobacco control policies and
      projects the effect of future policies on smoking and snus use prevalence and
      associated premature mortality in Sweden. METHODS: The established SimSmoke model
      was adapted with population, smoking rates and tobacco control policy data from
      Sweden. SimSmoke evaluates the effect of taxes, smoke-free air, mass media,
      marketing bans, warning labels, cessation treatment and youth access policies on
      smoking and snus prevalence and the number of deaths attributable to smoking and
      snus use by gender from 2010 to 2040. RESULTS: Sweden SimSmoke estimates that
      significant inroads to reducing smoking and snus prevalence and premature
      mortality can be achieved through tax increases, especially when combined with
      other policies. Smoking prevalence can be decreased by as much as 26% in the
      first few years, reaching a 37% reduction within 30 years. Without effective
      tobacco control policies, almost 54 500 lives will be lost in Sweden due to
      tobacco use by the year 2040. CONCLUSION: Besides presenting the benefits of a
      comprehensive tobacco control strategy, the model identifies gaps in surveillance
      and evaluation that can help better focus tobacco control policy in Sweden.

PMID- 24287031
TI  - Association of children's eating behaviors with parental education, and teachers'
      health awareness, attitudes and behaviors: a national school-based survey in
      China.
AB  - BACKGROUND: In China, childhood obesity is a growing health issue. Eating
      behaviors among children can be influenced by both the family and school
      environment. We examine the association between these environments and eating
      habits among children. METHODS: A total of 11 270 fourth to sixth grade school
      children, 11 270 of their fathers or mothers, and 1348 teachers from 48 schools
      were sampled using a multistage cluster random sampling method. Questionnaires
      collected information on eating behaviors among children, non-communicable
      chronic disease (NCD)-related health knowledge and behaviors among teachers, and
      education levels among parents. Mixed effect logistic regression models were used
      to describe the key associations between eating behaviors among children and
      teacher and parental characteristics. RESULTS: Health awareness, positive health
      attitudes, never-smoking and regular-exercise among teachers was positively
      associated with healthy eating behaviors among their students (having breakfast,
      vegetables and dairy products every day; P < 0.05), and negatively associated
      with the unhealthy behaviors (daily intake of fried foods and desserts and sugary
      beverages; P < 0.05). More than one parent having a high school level or above
      was positively related to healthy eating behaviors among their children (P <
      0.05), but its associations with high-calorie eating habits were negative in
      urban and positive in rural areas (P < 0.05). CONCLUSIONS: School-based
      interventions which target health-related awareness, attitude and behaviors among
      school teachers may help improve school-aged children's eating behaviors.
      Parental education levels may help guide efforts to target children at higher
      risk of unhealthy eating habits.

PMID- 24287032
TI  - Blood pressure among rural Montenegrin children in relation to poverty and
      gender.
AB  - BACKGROUND: Health inequalities may begin during childhood. The aim of this study
      was to investigate the main effect of poverty and its interactive effect with
      gender on children's blood pressure. METHODS: The study was performed in two
      elementary schools from a rural region near Podgorica, the capital of Montenegro.
      A questionnaire including questions on family monthly income, children's physical
      activity and the consumption of junk food was self-administered by parents of 434
      children (223 boys and 211 girls) aged 6-13 years. Children's poverty level was
      assessed using the recommendations from the National Study on Poverty in
      Montenegro. Children's body weight and height were measured and body mass index
      for-gender-and-age percentile was calculated. An oscillometric monitor was used
      for measurement of children's resting blood pressure in school. RESULTS: A two
      factorial analysis of variance with body mass index percentile, physical activity
      and junk food as covariates showed an interaction of gender and poverty on
      children's blood pressure, pointing to synergy between poverty and female gender,
      with statistical significance for raised diastolic pressure (F = 5.462; P =
      0.021). Neither physical activity nor the consumption of junk food explained the
      interactive effect of poverty and gender on blood pressure. CONCLUSION: We show
      that poverty is linked to elevated blood pressure for girls but not boys, and
      this effect is statistically significant for diastolic pressure. The results are
      discussed in the light of gender differences in stress and coping that are
      endemic to poverty.

PMID- 24287033
TI  - Transcatheter therapies for mitral regurgitation: a professional society overview
      from the American College of Cardiology, the American Association for Thoracic
      Surgery, Society for Cardiovascular Angiography and Interventions Foundation, and
      the Society of Thoracic Surgeons.

PMID- 24287035
TI  - Impact of angiogenic and innate immune systems on the corpus luteum function
      during its formation and maintenance in ruminants.
AB  - The corpus luteum (CL) is formed from an ovulated follicle, and grows rapidly to
      secrete progesterone (P4) thereby supporting implantation and maintenance of
      pregnancy. It is now evident that angiogenesis is necessary to form the structure
      of the developing CL as well as to acquire the steroidogenic capacity to secrete
      large amounts of P4. It is of interest that the increases in CL size, plasma P4
      concentration and luteal blood flow are occurring in parallel during the first
      seven days after ovulation. Angiogenic factors, such as vascular endothelial
      growth factor-A (VEGFA) and basic fibroblast growth factor (FGF2), play a central
      role in promoting cell proliferation and angiogenesis in the developing CL.
      Angiopoietins regulate the stability of blood vessels, which directly affects
      angiogenesis or angiolysis via angiogenic factors. Vasohibin-1 is a novel
      negative feedback regulator, which inhibits VEGF-based vasculogenesis. It became
      evident that the immune cells, i.e., macrophages, eosinophils and neutrophils are
      recruited into the CL - using the innate immune system - just after ovulation
      which is accompanied by bleeding. The immune cells support active angiogenesis
      and thus the growth of the CL. In cows, the lymphatic system, but not blood
      vascular system, is reconstituted during early pregnancy, and embryonic
      trophoblast-derived interferon tau could play a crucial role in inducing
      lymphangiogenesis. This novel phenomenon may support a maternal recognition of
      pregnancy in shifting the local systems in such a way that they ensure a long
      term supply of P4 over the period of pregnancy. Overall, the current findings
      support the concept that several major components involved in the regulation of
      the CL development and maintenance overlap in stimulating steroidogenesis,
      angiogenesis, vascular function and the innate immune system.

PMID- 24287034
TI  - Endocrine and local control of the primate corpus luteum.
AB  - The primate corpus luteum is a transient endocrine gland that differentiates from
      the ovulatory follicle midway through the ovarian (menstrual) cycle. Its
      formation and limited lifespan is critical for fertility, as luteal-derived
      progesterone is the essential steroid hormone required for embryo implantation
      and maintenance of intra-uterine pregnancy until the placenta develops. It is
      well-established that LH and the LH-like hormone, CG, are the vital luteotropic
      hormones during the menstrual cycle and early pregnancy, respectively. Recent
      advances, particularly through genome analyses and cellular studies, increased
      our understanding of various local factors and cellular processes associated with
      the development, maintenance and repression of the corpus luteum. These include
      paracrine or autocrine factors associated with angiogenesis (e.g., VEGF), and
      that mediate LH/CG actions (e.g., progesterone), or counteract luteotropic
      effects (i.e., local luteolysis; e.g., PGF2alpha). However, areas of mystery and
      controversy remain, particularly regarding the signals and events that initiate
      luteal regression in the non-fecund cycle. Novel approaches capable of gene
      "knockdown" or amplification", in vivo as well as in vitro, should identify novel
      or underappreciated gene products that are regulated by or modulate LH/CG actions
      to control the functional lifespan of the primate corpus luteum. Further advances
      in our understanding of luteal physiology will help to improve or control
      fertility for purposes ranging from preservation of endangered primate species to
      designing novel ovary-based contraceptives and treating ovarian disorders in
      women.

PMID- 24287036
TI  - The putative roles of nuclear and membrane-bound progesterone receptors in the
      female reproductive tract.
AB  - Progesterone produced by the corpus luteum (CL) is a key regulator of normal
      cyclical reproductive functions in the females of mammalian species. The
      physiological effects of progesterone are mediated by the canonical genomic
      pathway after binding of progesterone to its specific nuclear progesterone
      receptor (PGR), which acts as a ligand-activated transcription factor and has two
      main isoforms, PGRA and PGRB. These PGR isoforms play different roles in the
      cell; PGRB acts as an activator of progesterone-responsive genes, while PGRA can
      inhibit the activity of PGRB. The ratio of these isoforms changes during the
      estrous cycle and pregnancy, and it corresponds to the different levels of
      progesterone signaling occurring in the reproductive tract. Progesterone exerts
      its effects on cells also by a non-genomic mechanism by the interaction with the
      progesterone-binding membrane proteins including the progesterone membrane
      component (PGRMC) 1 and 2, and the membrane progestin receptors (mPRs). These
      receptors rapidly activate the appropriate intracellular signal transduction
      pathways, and subsequently they can initiate specific cell responses or modulate
      genomic cell responses. The diversity of progesterone receptors and their
      cellular actions enhances the role of progesterone as a factor regulating the
      function of the reproductive system and other organs. This paper deals with the
      possible involvement of nuclear and membrane-bound progesterone receptors in the
      function of target cells within the female reproductive tract.

PMID- 24287037
TI  - The Bax/Bcl-2 apoptotic pathway is not responsible for the increase in apoptosis
      in the RU486-treated rat uterus during early pregnancy.
AB  - An increase in apoptotic activity has been observed in both the rabbit and the
      rat endometria following treatment with RU486. The aim of this study was to
      assess whether Bax and Bcl-2 signaling, in response to RU486, could be crucial
      role players mediating apoptosis in the rat uterus during early pregnancy. RU486
      is a partial progesterone (P4) and estrogen receptor antagonist, functioning to
      actively silence P4 receptor gene-associated transcription. Although an increase
      in apoptosis as a result of RU486 administration has been previously reported in
      rabbits, the specific apoptotic factors and pathways involved in driving this
      process have not yet been established. Immunofluorescent techniques were used to
      determine protein expression levels of both Bax and Bcl-2 in RU486-treated
      endometria at days 4.5, 5.5 and 6.5 of pregnancy. The Bax/Bcl-2 index was used to
      determine the overall pro- or anti-apoptotic setting at each day of pregnancy,
      following RU486 administration. Changes in the Bax and Bcl-2 gene expression
      levels as a consequence of RU486 administration were evaluated using RT-qPCR.
      Both the protein and gene expression analyses suggest that RU486 induces a change
      toward an overall anti-apoptotic signal within the Bax/Bcl-2 pathway. These
      results suggest that the observed increase in apoptosis following RU486
      administration is not driven by a shift in the Bax/Bcl-2 ratio toward cell death,
      when the P4 and estrogen receptors are partially inactivated by RU486, but is
      possibly regulated by another apoptotic pathway.

PMID- 24287038
TI  - Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle
      regularity, and kisspeptin expression in female rats.
AB  - Kisspeptin, encoded by Kiss1, plays a key role in pubertal maturation and
      reproduction as a positive upstream regulator of the hypothalamic-pituitary
      gonadal (HPG) axis. To examine the role of high-fat diet (HFD) on puberty onset,
      estrous cycle regularity, and kisspeptin expression, female rats were exposed to
      HFD in distinct postnatal periods. Three groups of rats were exposed to HFD
      containing 60% energy from fat during the pre-weaning period (postnatal day (PND)
      1-16, HFD PND 1-16), post-weaning period (HFD PND 21-34), or during both periods
      (HFD PND 1-34). Puberty onset, evaluated by vaginal opening, was monitored on
      days 30-34. Leptin, estradiol (E2), Kiss1 mRNA levels, and number of kisspeptin
      immunoreactive cells in the anteroventral periventricular nucleus (AVPV) and
      arcuate nucleus (ARC) were measured at day 34. Body weight increased only in rats
      exposed to HFD during post-weaning period, whereas the timing of vaginal opening
      was unaffected in all three groups. Leptin, Kiss1 mRNA levels, and number of
      kisspeptin-immunoreactive cells at day 34 were not affected by HFD. Additionally,
      the estrous cycle regularity was monitored in rats exposed to HFD for 40 days
      from weaning. Leptin, E2, and Kiss1 mRNA levels in the AVPV and ARC were measured
      after the HFD exposure. Thirty-three percent of rats exposed to HFD exhibited
      irregular estrous cycles and a two-fold increase in leptin. By contrast, E2 level
      and Kiss1 mRNA levels were not affected by the treatment. These data show that
      postnatal HFD exposure induced irregular estrous cycles, but had no effect on
      puberty onset or kisspeptin.

PMID- 24287039
TI  - The involvement of peroxisome proliferator activated receptors (PPARs) in
      prostaglandin F2alpha production by porcine endometrium.
AB  - In the present study, we investigated the in vitro effects of peroxisome
      proliferator activated receptor (PPAR) ligands on PGF2alpha secretion and mRNA
      expression of prostaglandin F synthase (PGFS) in porcine endometrial explants
      collected on days 10-12 and 14-16 of the estrous cycle or pregnancy. The explants
      were incubated for 6h with: PPARalpha ligands - WY-14643 (agonist) and MK 886
      (antagonist); PPARbeta ligands - l-165,041 (agonist) and GW 9662 (antagonist);
      PPARgamma ligands - 15d-prostaglandin J2 (PGJ2, agonist), rosiglitazone (agonist)
      and T0070907 (antagonist). The expression of PGFS mRNA in the endometrium and the
      concentration of PGF2alpha in culture media were determined by real time RT-PCR
      and radioimmunoassay, respectively. During the estrous cycle (days 10-12 and 14
      16), the agonists - WY-14643 (PPARalpha), l-165,041 (PPARbeta), PGJ2 and
      rosiglitazone (PPARgamma) - increased PGF2alpha secretion but did not affect PGFS
      mRNA abundance. During pregnancy (days 10-12 and 14-16), PPARalpha and PPARgamma
      ligands did not change PGF2alpha release, whereas PPARbeta agonist augmented
      PGF2alpha release on days 14-16 of pregnancy. In addition, WY-14643 and l-165,041
      increased PGFS mRNA level in both examined periods of pregnancy. PPARgamma
      agonist (PGJ2) and antagonist (T0070907) enhanced PGFS mRNA abundance in the
      endometrium on days 10-12 and 14-16 of pregnancy, respectively. The results
      indicate that PPARs are involved in the production of PGF2alpha by porcine
      endometrium, and that the sensitivity of the endometrium to PPAR ligands depends
      on reproductive status of animals.

PMID- 24287040
TI  - Molecular identification and expression of FOXL2 and DMRT1 genes from willow
      minnow Gnathopogon caerulescens.
AB  - Willow minnow, Gnathopogon caerulescens, is a commercially important freshwater
      fish species in Japan. In particular, female fish with eggs are more expensive
      than male fish. Many methods have been tested to achieve 100% willow minnow
      female production; however, none of them were successful because of the
      temperature-dependent sex determination mechanism. To date, the molecular
      mechanism underlying sex determination in willow minnow is still not completely
      understood. This study was designed as an attempt to understand the sex
      differentiation mechanism of willow minnow at the molecular level. We cloned the
      mRNAs of two sex-related genes of G. caerulescens-forkhead-box protein L2 (FOXL2)
      and doublesex- and mab-3-related transcription factor 1 (DMRT1). We compared the
      inferred amino acid sequences to those of other fish and examined the expression
      patterns of these genes in adult tissues and during development. The FOXL2 and
      DMRT1 genes of willow minnow were isolated and identified. Both gene sequences
      share high homology with those of Chinese Cyprinidae. The cell- and tissue
      specific expression of FOXL2 and DMRT1 were also determined. Both genes were
      expressed in gonads, and their expression level increased before gonadal sex
      differentiation. Overall, these results suggest that these two genes play a key
      role in the sex differentiation of willow minnow. Detailed knowledge regarding
      this mechanism will be useful for efficient all-female cyprinid fish production
      that follows a temperature-dependent sex determination system.

PMID- 24287041
TI  - Assessment of the reproductive parameters, laparoscopic oocyte recovery and the
      first embryos produced in vitro from endangered Caninde goats (Capra hircus).
AB  - The Caninde breed of goats (Capra hircus) is currently endangered. The aims of
      this study were to characterize the estrus behavior, ovulatory responses and
      progesterone profiles, and to evaluate the in vitro embryo production (IVP) in
      this breed. In Experiment 1, ten nulliparous and seven pluriparous females
      received medroxyprogesterone acetate (MAP)-containing sponges (60mg) plus 75MUg d
      cloprostenol for estrus synchronization and their reproductive parameters were
      evaluated. In Experiment 2, oocytes obtained by laparascopy from hormonally
      stimulated females (n=15) were used for IVP. There was no difference (p>0.05)
      between nulliparous and pluriparous goats in terms of estrus response (40.0% vs.
      85.7%), time from progestagen sponge removal to the onset of estrus (62.0+/-15.5
      vs. 50.7+/-19.2h; mean+/-SEM), duration of estrus (25.0+/-16.1 vs. 30.0+/-15.1h),
      percentage of ovulating animals (60.0% vs. 85.7%), number of ovulations (1.2+/
      0.4 vs. 1.3+/-0.8), and diameter of the preovulatory follicle (5.8+/-0.5 vs.
      6.1+/-0.3mm). Progesterone concentrations were also similar (p>0.05) in both
      groups. During laparoscopic recovery, there were average 12.2 aspirated follicles
      and 9.1 oocytes per goat, resulting in a high recovery rate (74.3%, 182/245). A
      total of 78 embryos were produced (51.0%). The mean number of cells in the
      blastocysts at day 7 of in vitro culture was 170.3+/-12.5. In conclusion,
      nulliparous and pluriparous Caninde goats exhibited similar reproductive
      profiles. It was possible to produce embryos in vitro, allowing the instigation
      of an embryo bank for preservation of this breed.

PMID- 24287042
TI  - Expression of the c-Kit receptor in germ cells of the seminiferous epithelium in
      rats with hormonal imbalance.
AB  - The aim of the study was to investigate the effects of pharmacologically induced
      hormonal imbalance in adult male rats treated with letrozole and rats exposed to
      soya isoflavones on the testicular morphology and c-Kit receptor (c-Kit-R)
      expression in germ cells. The study was conducted during all developmental
      periods: prenatal period, lactation, youth, and sexual maturity. Morphological
      and morphometrical analyses were performed on testicular section, and c-Kit-R was
      identified using immunohistochemistry. In addition, concentration of circulating
      steroids was measured in mature rats exposed to soya isoflavones. A significant
      reduction in testosterone level in rats exposed to soya isoflavones, and the
      sloughing of the premature germ cells into the lumen of the seminiferous tubules
      in the testes of both groups of rats were observed. Immunohistochemistry showed a
      decrease in c-Kit-R expression in germ cells of both experimental groups.
      Morphometric analysis indicated a decreased thickness of the layers occupied by c
      Kit-R-positive spermatogonia, and a decreased diameter of the seminiferous
      tubules in the testes of both experimental groups of animals. In conclusion, the
      pharmacologically induced reduction of the estradiol level in adult rats and the
      diminished level of testosterone in rats exposed to soya isoflavones during the
      prenatal period, lactation and up to maturity caused similar morphological and
      functional changes associated with the decreased c-Kit-R expression in germ cells
      in the seminiferous epithelium. These findings demonstrate the importance of the
      estrogen/androgen balance for normal testicular morphology and spermatogenesis.

PMID- 24287043
TI  - Sex-sorting of boar spermatozoa does not influence the localization of glucose
      transporters.
AB  - Sex-sorting damages spermatozoa function, shortening their lifespan and
      fertility. This study used an immunofluorescence technique to investigate the
      effect of sex-sorting on the localization of glucose transporters (GLUTs) in boar
      spermatozoa. GLUTs are trans-membrane proteins responsible for glucose transport
      within cells. Distribution of GLUTs on sperm cells was similar in unsorted and
      sex-sorted semen, suggesting that the flow cytometric sex-sorting process did not
      affect the sperm energy apparatus.

PMID- 24287044
TI  - Influence of lysophosphatidic acid on estradiol production and follicle
      stimulating hormone action in bovine granulosa cells.
AB  - The objective of the study was to examine the effect of lysophosphatidic acid
      (LPA) on 17beta-estradiol (E2) synthesis and follicle stimulating hormone (FSH)
      action in bovine granulosa cells. We found that granulosa cells in the bovine
      antral follicle, in addition to the uterus and the CL, are also the site of LPA
      synthesis and the target for LPA action in the bovine reproductive tract. Our
      findings suggest that LPA stimulates E2 synthesis, probably via increased
      expression of FSHR and 17beta-HSD genes.

PMID- 24287045
TI  - Preparing breast cancer patients for survivorship (PREP) - a pilot study of a
      patient-centred supportive group visit intervention.
AB  - PURPOSE: The process of breast cancer follow-up has psychosocial benefits for
      patients, notably reassurance, although attending hospital appointments can
      increase anxiety. Discharge from hospital follow-up can also invoke anxiety as
      many patients seek reassurance from continued specialist follow-up. Inevitably,
      due to increased survival and associated resource issues, opportunities for
      follow-up and support will be reduced. We delivered and evaluated an intervention
      which supported the transition from cancer patient to cancer survivor, for breast
      cancer patients being discharged to primary care. METHODS: We delivered and
      evaluated a pilot of a patient-centred group intervention 'Preparing Patients for
      Discharge', aimed at reducing distress. Between January and September 2008, 172
      participants were recruited and 74 (43%) expressed an interest in participating
      in the intervention; 32 of 74 took part, and participated in its evaluation using
      a semi-structured evaluation questionnaire, standardized measures [Hospital
      Anxiety and Depression Scale (HADS) and Clinical Outcomes for Routine Evaluation
      (CORE)] and independent qualitative interviews. RESULTS: The qualitative analysis
      of questionnaire data indicated key factors were 1) shared experience, 2) support
      and reassurance, and 3) positive views about cancer and being discharged. The
      interview data revealed that the intervention enabled participants to: share
      experiences, focus on emotional needs, and have open discussions about
      recurrence, while increasing confidence in being discharged and using alternative
      support services. However, no significant differences were found in pre-post
      interventions scores of HADS and CORE. CONCLUSIONS: Providing a structured group
      intervention approach for breast cancer patients offers an early opportunity to
      support cancer survivors and facilitate and encourage self-management.

PMID- 24287046
TI  - Quantitative transmission characteristics of different H5 low pathogenic avian
      influenza viruses in Muscovy ducks.
AB  - EU annual serosurveillance programs show that domestic duck flocks have the
      highest seroprevalence of H5 antibodies, demonstrating the circulation of
      notifiable avian influenza virus (AIV) according to OIE, likely low pathogenic
      (LP). Therefore, transmission characteristics of LPAIV within these flocks can
      help to understand virus circulation and possible risk of propagation. This study
      aimed at estimating transmission parameters of four H5 LPAIV (three field strains
      from French poultry and decoy ducks, and one clonal reverse-genetics strain
      derived from one of the former), using a SIR model to analyze data from
      experimental infections in SPF Muscovy ducks. The design was set up to
      accommodate rearing on wood shavings with a low density of 1.6 ducks/m(2): 10
      inoculated ducks were housed together with 15 contact-exposed ducks. Infection
      was monitored by RNA detection on oropharyngeal and cloacal swabs using real-time
      RT-PCR with a cutoff corresponding to 2-7 EID50. Depending on the strain, the
      basic reproduction number (R0) varied from 5.5 to 42.7, confirming LPAIV could
      easily be transmitted to susceptible Muscovy ducks. The lowest R0 estimate was
      obtained for a H5N3 field strain, due to lower values of transmission rate and
      duration of infectious period, whereas reverse-genetics derived H5N1 strain had
      the highest R0. Frequency and intensity of clinical signs were also variable
      between strains, but apparently not associated with longer infectious periods.
      Further comparisons of quantitative transmission parameters may help to identify
      relevant viral genetic markers for early detection of potentially more virulent
      strains during surveillance of LPAIV.

PMID- 24287047
TI  - Structural, spectroscopic, and nonlinear optical investigations on a novel
      nonlinear optical crystal: hippuric acid doped ammonium di hydrogen phosphate
      (HAADP).
AB  - Transparent single crystals of pure and 1 mol% hippuric acid doped ammonium di
      hydrogen phosphate (HAADP) were grown from aqueous solution by employing slow
      evaporation technique. Crystallinity of the grown crystals was studied by powder
      X-ray diffraction analysis. Both pure ADP and HAADP crystals exhibit tetragonal
      crystal structure. The bonding structure and molecular associations due to
      chemical reactions were analyzed by FTIR spectroscopy. It also confirms the
      functional groups present in the grown crystals. UV-Vis-NIR spectral analysis was
      carried out to study the optical characteristics of the crystals which reveal
      that the cutoff wavelength for both pure and hippuric acid doped ADP crystal is
      around 300 nm. From these spectra it can be clearly inferred that there is an
      absence of characteristic absorption in the region between 340 and 1200 nm, which
      is a most desirable property of a material for both SHG and other NLO
      applications. Second harmonic generation (SHG) test adopting the Kurtz Perry
      technique revealed that the second harmonic generation efficiency of HAADP is 1.5
      times that of pure ADP crystal.

PMID- 24287048
TI  - Spectral studies of multi-branched fluorescence dyes based on triphenylpyridine
      core.
AB  - A series of novel triphenylpyridine-containing triphenylamine derivatives have
      been carefully designed and prepared in good yields using the stepwise route
      reactions. The relationship of photoluminescence property and structure of
      compounds 9-13 was systematically investigated via UV-vis, fluorescence,
      thermogravimetric and electrochemical analyzer. The highest occupied molecular
      orbital and the lowest unoccupied molecular orbital distributions of compounds 9
      13 were calculated by density functional theory method. The high fluorescence
      quantum yields, desirable the highest occupied molecular orbital levels and high
      thermal stability of compounds 9-13 indicate that the linkage of
      triphenylpyridine and triphenylamine is an efficient means to enhance hole
      transporting ability and fluorescent quantum yield. 

PMID- 24287049
TI  - Spectroscopic (FT-IR, FT-Raman) investigations and quantum chemical calculations
      of 4-hydroxy-2-oxo-1,2-dihydroquinoline-7-carboxylic acid.
AB  - Quinoline derivatives have good nonlinear optical properties and have been
      extensively studied due to their great potential application in the field of
      organic light emitting diodes. Quantum chemical calculations of the equilibrium
      geometry, harmonic vibrational frequencies, infrared intensities and Raman
      activities of 4-hydroxy-2-oxo-1,2-dihydroquinoline-7-carboxylic acid in the
      ground state were reported. Potential energy distribution of normal modes of
      vibrations was done using GAR2PED program. The synthesis, (1)H NMR and PES scan
      results are also discussed. Nonlinear optical behavior of the examined molecule
      was investigated by the determination of first hyperpolarizability. The
      calculated HOMO and LUMO energies show the chemical activity of the molecule. The
      stability of the molecule arising from hyperconjugative interaction and charge
      delocalization has been analyzed using NBO analysis. The calculated geometrical
      parameters are in agreement with that of similar derivatives. 

PMID- 24287050
TI  - Analytical Raman spectroscopy in a forensic art context: the non-destructive
      discrimination of genuine and fake lapis lazuli.
AB  - The differentiation between genuine and fake lapis lazuli specimens using Raman
      spectroscopy is assessed using laboratory and portable instrumentation operating
      at two longer wavelengths of excitation in the near-infrared, namely 1064 and 785
      nm. In spite of the differences between the spectra excited here in the near
      infrared and those reported in the literature using visible excitation, it is
      clear that Raman spectroscopy at longer wavelengths can provide a means of
      differentiating between the fakes studied here and genuine lapis lazuli. The
      Raman spectra obtained from portable instrumentation can also achieve this
      result, which will be relevant for the verification of specimens which cannot be
      removed from collections and for the identification of genuine lapis lazuli
      inlays in, for example, complex jewellery and furniture. The non-destructive and
      non-contact character of the technique offers a special role for portable Raman
      spectroscopy in forensic art analysis.

PMID- 24287051
TI  - Study of vibrational spectra, normal coordinate analysis and molecular structure
      of 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine using density functional
      theory.
AB  - In the present analysis, the FT-IR, FT-Raman spectra of 6-(2,3-dichlorophenyl)
      1,2,4 triazine-3,5-diamine (DCTDA) have been recorded in the region 4000-450 cm(
      1) and 4000-100 cm(-1) respectively. The stable structure geometry of the
      isolated molecule in the gas phase was investigated theoretically using density
      functional theory (B3LYP) with 6-311G(d,p) basis set. The assignment of the
      vibrational spectra has been calculated to aid with normal coordinate analysis
      (NCA) following the scaled quantum mechanical force field methodology (SQMF). UV
      Vis spectra of the compound was recorded in water solvent and the electronic
      properties, such as HOMO and LUMO energies were calculated by time-dependent
      density functional theory (TD-DFT) approach. The various intramolecular
      interactions which are responsible for the stabilization of the molecule were
      revealed by the natural bond orbital analysis. The molecule orbital contributions
      are studied by density of energy states (DOS). The other molecular properties
      like molecular electrostatic potential (MEP), NLO and thermodynamic properties of
      the title compound at different temperatures have been calculated. Finally the
      calculation results were applied to stimulate infrared and Raman spectra of the
      title compound which show good agreement with observed spectra.

PMID- 24287052
TI  - Direct visual evidence for chemical mechanism of SERRS of the S-complex of
      pyrimidine molecule adsorbed on silver nanoparticle via charge transfer.
AB  - In this paper, the S-complex of pyrimidine molecule absorbed on silver clusters
      was employed as a model molecule to study the enhancement mechanism in surface
      enhanced resonance Raman scattering (SERRS). We described the chemical
      enhancement of SERRS through charge transfer (CT) from Ag20 to pyrimidine on
      resonance excitation, and electromagnetic enhancement through intracluster charge
      redistribution (CR) on the electronic intracluster collective oscillation
      excitation. It is shown that SERRS process of the pyrimidine molecule absorbed on
      silver clusters with different incident wavelength are dominated by different
      enhancement mechanisms. Both experimental and theoretical works have been
      performed to understand the CT process in SERRS. 

PMID- 24287053
TI  - Acid-base properties, FT-IR, FT-Raman spectroscopy and computational study of 1
      (pyrid-4-yl)piperazine.
AB  - We report the vibrational spectral analysis was carried out using FT-IR and FT
      Raman spectroscopy for 1-(pyrid-4-yl)piperazine (PyPi). Single crystals of PyPi
      suitable for X-ray structural analysis were obtained. The acid-base properties
      are also reported. PyPi supported on a weak acid cation-exchanger in the single
      protonated form and this system can be used efficiently as the solid supported
      analogue of 4-N,N-dimethyl-aminopyridine. The complete vibrational assignments of
      wavenumbers were made on the basis of potential energy distribution. The HOMO and
      LUMO analysis is used to determine the charge transfer within the molecule and
      with the molecular electrostatic potential map was applied for the reactivity
      assessment of PyPi molecule toward proton, electrophiles and nucleopholes as
      well. The stability of the molecule arising from hyper-conjugative interaction
      and charge delocalization has been analyzed using NBO analysis. The calculated
      first hyperpolarizability of PyPi is 17.46 times that of urea. 

PMID- 24287054
TI  - Vibrational spectroscopic, 1H NMR and quantum chemical computational study of 4
      hydroxy-2-oxo-1,2-dihydroquinoline-8-carboxylic acid.
AB  - FT-IR, FT-Raman and (1)H NMR spectra of 4-hydroxy-2-oxo-1,2-dihydroquinoline-8
      carboxylic acid were recorded and obtained data were confronted with the computed
      using Gaussian09 software package. DFT/B3LYP, B3PW91 calculations have been done
      using 6-31G* and SDD basis sets, to investigate the vibrational frequencies and
      geometrical parameters. The assignments of the normal modes are done by potential
      energy distribution (PED) calculations. The calculated first hyperpolarizability
      is comparable with the reported values of similar quinoline derivatives and is an
      attractive object for future studies of non-linear optics. The stability of the
      molecule arising from hyperconjugative interaction and charge delocalization has
      been analyzed using NBO analysis. MEP predicts the most reactive part in the
      molecule. The calculated (1)H NMR results are in good agreement with experimental
      data.

PMID- 24287055
TI  - The analytical investigations of ancient pottery from Kaveripakkam, Vellore dist,
      Tamilnadu by spectroscopic techniques.
AB  - Analytical investigations using Fourier Transform infrared spectroscopy (FT-IR),
      Powder X-ray Diffraction (PXRD), Thermal Analysis (TG-DTA), Scanning Electron
      Microscopy (SEM) and Energy Dispersive X-ray Fluorescence Spectrometry (EDXRF)
      were carried out on ancient pottery fragments from Kaveripakkam, in order to
      outline manufacturing skills, technology information, firing condition and
      temperature of potteries. The whole set of data showed the firing temperature in
      the range of 800-900 degrees C. The analytical characterization of the potsherds,
      by different complimentary techniques has allowed to identifying the raw
      materials and technology applied by the ancient artisans. 

PMID- 24287056
TI  - Quantum chemical study on influence of intermolecular hydrogen bonding on the
      geometry, the atomic charges and the vibrational dynamics of 2,6
      dichlorobenzonitrile.
AB  - FT-IR (4000-400 cm(-1)) and FT-Raman (4000-200 cm(-1)) spectral measurements on
      solid 2,6-dichlorobenzonitrile (2,6-DCBN) have been done. The molecular geometry,
      harmonic vibrational frequencies and bonding features in the ground state have
      been calculated by density functional theory at the B3LYP/6-311++G (d,p) level. A
      comparison between the calculated and the experimental results covering the
      molecular structure has been made. The assignments of the fundamental vibrational
      modes have been done on the basis of the potential energy distribution (PED). To
      investigate the influence of intermolecular hydrogen bonding on the geometry, the
      charge distribution and the vibrational spectrum of 2,6-DCBN; calculations have
      been done for the monomer as well as the tetramer. The intermolecular interaction
      energies corrected for basis set superposition error (BSSE) have been calculated
      using counterpoise method. Based on these results, the correlations between the
      vibrational modes and the structure of the tetramer have been discussed.
      Molecular electrostatic potential (MEP) contour map has been plotted in order to
      predict how different geometries could interact. The Natural Bond Orbital (NBO)
      analysis has been done for the chemical interpretation of hyperconjugative
      interactions and electron density transfer between occupied (bonding or lone
      pair) orbitals to unoccupied (antibonding or Rydberg) orbitals. UV spectrum was
      measured in methanol solution. The energies and oscillator strengths were
      calculated by Time Dependent Density Functional Theory (TD-DFT) and matched to
      the experimental findings. TD-DFT method has also been used for theoretically
      studying the hydrogen bonding dynamics by monitoring the spectral shifts of some
      characteristic vibrational modes involved in the formation of hydrogen bonds in
      the ground and the first excited state. The (13)C nuclear magnetic resonance
      (NMR) chemical shifts of the molecule were calculated by the Gauge independent
      atomic orbital (GIAO) method and compared with experimental results. Standard
      thermodynamic functions have been obtained and changes in thermodynamic
      properties on going from monomer to tetramer have been presented.

PMID- 24287057
TI  - Recombinant vaccines against bluetongue virus.
AB  - Bluetongue (BT) is a hemorrhagic disease of ruminants caused by bluetongue virus
      (BTV), the prototype member of the genus Orbivirus within the family Reoviridae
      and is transmitted via biting midges of the genus Culicoides. BTV can be found on
      all continents except Antarctica, and up to 26 immunologically distinct BTV
      serotypes have been identified. Live attenuated and inactivated BTV vaccines have
      been used over the years with different degrees of success. The multiple
      outbreaks of BTV in Mediterranean Europe in the last two decades and the
      incursion of BTV-8 in Northern Europe in 2008 has re-stimulated the interest to
      develop improved vaccination strategies against BTV. In particular, safer, cross
      reactive, more efficacious vaccines with differential diagnostic capability have
      been pursued by multiple BTV research groups and vaccine manufacturers. A wide
      variety of recombinant BTV vaccine prototypes have been investigated, ranging
      from baculovirus-expressed sub-unit vaccines to the use of live viral vectors.
      This article gives a brief overview of all these modern approaches to develop
      vaccines against BTV including some recent unpublished data. 

PMID- 24287058
TI  - Trypan blue: is it suitable for staining of the endometrium?

PMID- 24287059
TI  - Uterine cavity calcifications: a report of 7 cases and a systematic literature
      review.
AB  - We report 7 uterine cavity calcification cases and systematically review the
      literature on cases presenting this finding. In our series of cases, the mean age
      of patients was 31.6 +/- 5.4 years, with an infertility period ranging from 2 to
      8 years. None of our patients had a history of intrauterine contraceptive device
      use, and 3 had undergone operative termination of pregnancy. Diagnostic and
      therapeutic hysteroscopy with complete removal of the calcifications was
      performed in all patients with fertility restoration in 5 of them. Our review
      included 35 articles published from 1989 to 2013 reporting endometrial
      calcification cases, with a total of 85 cases. Analyzed variables included
      patient age, abortion antecedents, clinical presentation, diagnostic method,
      treatment, and outcome. The mean age of the analyzed cases was 34.3 years,
      ranging from 19 to 62 years. Abortion antecedents were present in most patients
      (76.5%). The most frequently used diagnostic methods were ultrasound (88.5% of
      articles) and hysteroscopy (85.7%). Regarding the clinical presentation,
      infertility was the most common feature (72.9% of cases) followed by menstrual
      abnormalities (30.3%). Hysteroscopic removal, whether alone or combined with
      other techniques, was the most used method for the removal of osseous tissue
      (70.6% of cases) followed by curettage (27.1%). After removal of the bony
      fragments, 55.6% of the infertile patients achieved a pregnancy. A total of 14
      cases reported relief of symptoms other than infertility. All of the data
      concerning outcome were stratified according to the treatment modality used. We
      conclude that endometrial calcifications in the uterine cavity are a relevant
      cause of secondary infertility, which can generally be properly diagnosed and
      treated through hysteroscopy, with successful restoration of fertility in most
      cases. 

PMID- 24287060
TI  - Indirectly detected heteronuclear correlation solid-state NMR spectroscopy of
      naturally abundant 15N nuclei.
AB  - Two-dimensional indirectly detected through-space and through-bond (1)H{(15)N}
      solid-state NMR experiments utilizing fast magic angle spinning (MAS) and
      homonuclear multipulse (1)H decoupling are evaluated. Remarkable efficiency of
      polarization transfer can be achieved at a MAS rate of 40 kHz by both cross
      polarization and INEPT, which makes these methods applicable for routine
      characterizations of natural abundance solids. The first measurement of 2D
      (1)H{(15)N} HETCOR spectrum of natural abundance surface species is also
      reported.

PMID- 24287061
TI  - Building the world's supply of quinine: Dutch colonialism and the origins of a
      global pharmaceutical industry.
AB  - Quinine, a naturally occurring alkaloid from the Cinchona tree, was one of the
      first drugs produced and sold by a global pharmaceutical industry during the
      nineteenth century. Factories in Europe and North America dominated the
      manufacturing industry, and between 1890 and 1940, Cinchona plantations on Java
      supplied most of the bark for the quinine pharmaceutical business. At the end of
      the nineteenth century, the Dutch colonial state kept a hands-off approach to the
      Cinchona enterprises, in keeping with its liberal orientation. But the persistent
      low-price for bark, which led to the near ruin of the Cinchona planters,
      eventually pushed the colonial state to actively protect the Cinchona
      plantations. Colonial officials sought to stabilize the colonial Cinchona export
      business by encouraging the integration of the quinine industry on a global
      scale. Most important was the colonial state's sponsorship in 1913 of the Quinine
      Agreement, establishing a set price for Cinchona bark, which created the world's
      first pharmaceutical cartel. In the interwar period, an alliance of Dutch
      government officials, planters, scientists, doctors and drug-makers, working in
      both the motherland and the colony, actively promoted the expansion of quinine
      consumption, as well as the merit of the Quinine Agreement, which they argued
      supplied guaranteed a steady supply of quinine, all for the wellbeing of global
      humanity.

PMID- 24287062
TI  - Deaths from adverse events are halved in Dutch hospitals.

PMID- 24287063
TI  - First Hodgkin cell line L428 and the CD30 antigen: their role for diagnostic and
      treatment of CD30-positive neoplasms.
AB  - Hodgkin's disease (HD) is a fatal disorder with the unique histologic features of
      few dysplastic Hodgkin- and Reed-Sternberg (HRS) cells surrounded by an abundance
      of nonatypical bystander cells in primary biopsies. By using the first Hodgkin
      cell line L428 the cytokine receptor CD30 was discovered. CD30 proved to be an
      excellent target for the diagnoses of CD30+ malignancies and for monoclonal
      antibody therapy in patients with these malignancies because of its highly
      restricted expression in healthy individuals. Recently, a new anti-CD30-toxin
      drug-conjugate consisting of an anti-CD30 monoclonal antibody bound to the
      nonimmunogenic toxin auristatin E with a newly designed linker was generated. 

PMID- 24287064
TI  - Advancing antibody drug conjugation: from the laboratory to a clinically approved
      anticancer drug.
AB  - The concept of using monoclonal antibodies for delivering drugs to cancer cells
      has been explored for decades, with early work surrounding nonspecific targets
      and drugs with low potencies. These studies underscored the importance of
      critical parameters, such as antigen and tumor target selection, linker
      stability, drug potency, pharmacokinetics, and conjugation methodology, in
      developing effective antibody drug conjugates with acceptable safety profiles.
      Brentuximab vedotin represents the culmination of much research and development
      activities in which many of these parameters were addressed. This article
      provides an overview of many studies that led to the development of this highly
      active antibody drug conjugate. 

PMID- 24287065
TI  - Brentuximab vedotin for the treatment of patients with Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is a relatively rare but highly curable human cancer.
      Because very few patients relapse and will require subsequent therapy, new drug
      development for HL has not been seen as a high priority by the pharmaceutical
      industry. Brentuximab vedotin, an antibody-drug conjugate that targets CD30
      receptors, became the first drug to be approved by regulatory agencies for the
      treatment of HL in more than 30 years. This review summarizes the current and
      future directions of incorporating brentuximab vedotin in the management of
      patients with HL.

PMID- 24287066
TI  - Combination chemoradiotherapy in early Hodgkin lymphoma.
AB  - Combination chemoradiotherapy achieves excellent results for the treatment of
      localized Hodgkin lymphoma. However, late toxic effects occur, mostly related to
      the radiotherapy administered after the standard adriamycin, bleomycin,
      vinblastine, and dacarbazine (ABVD) chemotherapy. The most serious sequelae are
      radiation-induced secondary cancers. Reducing radiotherapy has not yet prevented
      late malignancies. However, when radiotherapy was omitted, tumor control was
      inferior, with more relapses necessitating rescue treatment including high-dose
      chemotherapy with stem cell support. Early fluorodeoxyglucose positron emission
      tomography performed after a few cycles of ABVD is evaluated in several
      randomized trials to identify patients who might be safely treated with
      chemotherapy alone. 

PMID- 24287067
TI  - Balancing risks and benefits of therapy for patients with favorable-risk limited
      stage Hodgkin lymphoma: the role of doxorubicin, bleomycin, vinblastine, and
      dacarbazine chemotherapy alone.
AB  - Because long-term survival of patients with nonbulky stage IA to IIA Hodgkin
      lymphoma is dependent on disease control and avoidance of late toxic effects
      associated with the treatment received, the initial choice of treatment can be
      associated with trade-offs that balance optimum disease control with avoidance of
      these late effect risks. Health professionals and patients face the dilemma of
      making treatment decisions without the benefit of completely understanding the
      risk-benefit balances associated with how current treatments affect all outcomes
      of interest. Optimum management of these patients requires careful
      multidisciplinary evaluation and communication strategies that account for
      patient preferences. 

PMID- 24287068
TI  - Early intensification treatment approach in advanced-stage Hodgkin lymphoma.
AB  - The key question in advanced-stage Hodgkin lymphoma for many years now has been,
      should intensified chemotherapy be applied upfront or be reserved for relapsing
      patients. The early intensification approach with BEACOPP(escalated) (bleomycin,
      etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
      aims at curing patients with first-line chemotherapy definitely. The added
      toxicity of this approach as compared to less intensive regimens as ABDV
      (doxorubicin, bleomycin, dacarbazine, vinblastine) is mainly restricted to acute
      haematotoxicity and gonadal damage. However, regarding efficacy, there is a
      meaningful survival-benefit over ABVD (10% at 5years) and the intensified first
      line treatment strategy is thus rightly regarded as standard of care.

PMID- 24287069
TI  - Induction therapy for advanced-stage Hodgkin lymphoma: late intensification (ABVD
      chemotherapy followed by high-dose chemotherapy and autologous stem cell
      transplant only for those who relapse).
AB  - The goal of therapy for patients with advanced-stage Hodgkin lymphoma is to
      ensure that as many patients as possible are healthy and free of disease decades
      after completing treatment. To achieve this, the treating physician needs to
      select the most effective therapeutic regimen, but also needs to choose a
      treatment strategy that limits long-term toxicity. One approach to achieve this
      is to use a less intense combination, such as ABVD chemotherapy, as initial
      treatment and intensify therapy only in those patients who do not become PET
      negative or who subsequently relapse. 

PMID- 24287070
TI  - FDG-PET response-adapted therapy: is 18F-fluorodeoxyglucose positron emission
      tomography a safe predictor for a change of therapy?
AB  - Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography
      (CT) is the most accurate tool for staging, treatment monitoring, and response
      evaluation in Hodgkin lymphoma (HL). Early determination of treatment sensitivity
      by FDG-PET is the best tool to guide individualized, response-adapted treatment.
      Several ongoing or recently completed trials have investigated the use of FDG
      PET/CT for early response-adapted HL therapy. The results are encouraging, but
      the data are immature, and PET response-adapted HL therapy is discouraged outside
      the setting of clinical trials. PET/CT looks promising for selection of therapy
      in relapsed and refractory disease, but the role in this setting is still
      unclear. 

PMID- 24287072
TI  - Relapsed/refractory Hodgkin lymphoma: what is the best salvage therapy and do we
      need RIC-alloSCT?
AB  - For relapsed-refractory Hodgkin Lymphoma, standard therapy consists of salvage
      chemotherapy followed by autologous stem cell transplantation. Adverse risk
      factors at relapse include response duration less than 12 months, advanced stage,
      extranodal disease, "B" symptoms and anemia. There is no obvious superior salvage
      regimen although maintaining dose-intensity is important for optimal responses.
      Assessment of response to salvage using FDG-PET identifies a distinct poor risk
      group, especially those with extranodal disease. Either a second salvage regimen
      or a tandem autologous transplant may benefit some patients with residual disease
      post-salvage. Reduced-intensity allografting may provide durable responses for
      some patients relapsing post-autologous transplant. 

PMID- 24287071
TI  - Customized targeted therapy in Hodgkin lymphoma: hype or hope?
AB  - Although most patients with Hodgkin lymphoma (HL) are cured with primary therapy,
      patients with primary refractory disease or relapse after initial treatment have
      poor outcomes and represent an unmet medical need. Recent advances in unraveling
      the biology of HL have yielded a plethora of novel targeted therapies. This
      review provides an overview of the data behind the hype generated by these
      advances and addresses the question of whether or not clinically these targeted
      therapies offer hope for patients with HL. 

PMID- 24287073
TI  - Hematology/Oncology Clinics of North America. Hodgkin lymphoma. Preface.

PMID- 24287075
TI  - Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I
      inhibitor: in vitro DNA binding, nuclease and RBC hemolysis.
AB  - Metal-based cancer chemotherapeutic agent of the type Co(II) complex
      [Co(mpca)2].H2O (1), where, Hmpca = 9-methyl-[1,10]phenanthroline-2-carboxylic
      acid was synthesized and characterized by various spectroscopic and analytical
      techniques and further authenticated by single crystal X-ray diffraction methods.
      In vitro DNA binding studies of complex 1 with CT DNA was carried out by several
      biophysical techniques in accordance with molecular docking technique which
      revealed that 1 binds to DNA via intercalation mode having GC-rich sequences.
      Complex 1 cleaves pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase
      assay). Furthermore, complex 1 exhibits significant inhibitory effects on the
      catalytic activity of Topo-I at 25 MUM concentration and further validated by
      molecular docking studies.

PMID- 24287076
TI  - [Liver injury induced by linagliptine and sitagliptine: it' a class effect?].

PMID- 24287077
TI  - A randomized phase III trial exploring the prognostic value of extensive
      intraoperative peritoneal lavage in addition to standard treatment for resectable
      advanced gastric cancer: CCOG 1102 study.
AB  - A randomized controlled trial has started in Japan to evaluate the efficacy of
      extensive intraoperative peritoneal lavage in the treatment of resectable
      advanced gastric cancer. Patients with T3 or deeper carcinoma of the stomach are
      intraoperatively randomized to either extensive intraoperative peritoneal lavage
      + arm or extensive intraoperative peritoneal lavage- arm. A total of 300 patients
      will be accrued from 20 institutions. The primary endpoint is disease-free
      survival, and secondary end-points are overall survival, peritoneal recurrence
      free survival and incidence of adverse events. 

PMID- 24287078
TI  - Etiology, characteristics and outcome of seizures after pediatric hematopoietic
      stem cell transplantation.
AB  - PURPOSE: Epileptic seizures are frequent manifestations after hematopoietic stem
      cell transplantation (HSCT). In this retrospective single-center study we
      evaluated electroclinical features and analyzed etiologies and outcome of
      seizures after pediatric HSCT. METHODS: Of 261 children transplanted between 2000
      and 2010, we identified and analyzed data of 28 patients with seizures within a
      year from HSCT. RESULTS: Most frequent etiologies were posterior reversible
      encephalopathy syndrome (PRES, 14 patients) and central nervous system (CNS)
      infections (4 patients). Seizures were the presentation of the underlying
      complications in 22 patients. Sixteen episodes of status epilepticus were
      identified. Seizures secondary to PRES were usually longer and associated with
      non-convulsive signs. Early neuroimaging and EEG monitoring proved to be crucial
      to diagnose and treat seizures and their causes. No patients developed epilepsy
      suggesting that chronic antiepileptic therapy is not necessary in these patients.
      Overall survival was 32.3% over 5 years in patients with seizures and 45.8% in
      patients without seizures (p<0.05). Multivariate statistical analysis identified
      as independent risk factors for seizures a diagnosis of non-oncological disease
      and cord blood stem cell transplantation. CONCLUSIONS: Seizures in transplanted
      children are a severe event and are associated with high morbidity and poor
      outcome. In particular, patients with non-oncological diseases and cord blood
      stem cell transplantation have to be considered at high risk of seizures.
      Moreover, this study underlines the importance of early recognition of non
      convulsive clinical signs and of EEG monitoring for a prompt diagnosis and an
      appropriate management of seizures and their causes.

PMID- 24287079
TI  - Seizure semiology and electroencephalography in young children with lesional
      temporal lobe epilepsy.
AB  - PURPOSE: This study aimed to discuss the clinical features of seizure semiology
      and electroencephalography (EEG) in young children with lesional temporal lobe
      epilepsy (TLE). METHOD: Children with lesional TLE received presurgical
      evaluation for intractable epilepsy. They were followed up for more than one year
      after temporal lobectomy. We reviewed the medical history and video-EEG
      monitoring of children with TLE to analyze the semiology of seizures and EEG
      findings and compared the semiology of seizures and EEG findings of childhood TLE
      and adult TLE. RESULTS: A total of 84 seizures were analyzed in 11 children (aged
      23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of
      17.6 months). All of the patients exhibited prominent motor manifestations
      including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven
      children manifested behavioral arrest similar to an automotor seizure in adult
      TLE but with a shorter duration and higher frequency. The automatisms were
      typically orofacial, whereas manual automatisms were rarely observed. The EEG
      recordings revealed that diffuse discharge patterns were more common in younger
      children, whereas focal or unilateral patterns were more typical in older
      children. All of the patients were seizure-free after temporal lobectomy with
      more than one-year follow-up. All of the children had a mental development delay
      or regression; however, there was improvement after surgery, especially in those
      with surgery performed early. CONCLUSION: In contrast to TLE in adults, young
      children with lesional TLE probably represent a distinct nosological and probably
      less homogeneous syndrome. Although they had generalized clinical and
      electrographic features, resective epilepsy surgery should be considered as early
      as possible to obtain seizure control and improvement in mental development.

PMID- 24287080
TI  - Hydrophobin-coated plates as matrix-assisted laser desorption/ionization sample
      support for peptide/protein analysis.
AB  - Fungal hydrophobins are amphipathic self-assembling proteins. Vmh2 hydrophobin,
      prepared from mycelial cultures of the basidiomycete fungus Pleurotus ostreatus,
      spontaneously forms a stable and homogeneous layer on solid surfaces and is able
      to strongly absorb proteins even in their active forms. In this work, we have
      exploited the Vmh2 self-assembled layer as a novel coating of a matrix-assisted
      laser desorption/ionization (MALDI) steel sample-loading plate. Mixtures of
      standard proteins, as well as tryptic peptides, in the nanomolar-femtomolar range
      were analyzed in the presence of salts and denaturants. As evidence on a real
      complex sample, crude human serum was also analyzed and spectra over a wide mass
      range were acquired. A comparison of this novel coating method with both standard
      desalting techniques and recently reported on-plate desalting methods was also
      performed. The results demonstrate that Vmh2 coating of MALDI plates allows for a
      very simple and effective desalting method suitable for development of lab-on-a
      plate platforms focused on proteomic applications. 

PMID- 24287081
TI  - Investigation of the correlation between charge and glycosylation of IgG1
      variants by liquid chromatography-mass spectrometry.
AB  - A recombinant IgG1 monoclonal antibody (mAb) showed multiple charge variants in a
      cation exchange chromatography profile. To better understand the correlation
      between charge heterogeneity and glycosylation, a rapid reversed phase ultra
      performance liquid chromatography-mass spectrometry (UPLC-MS) method with
      integrated mass analysis has been developed for simultaneous determination of N
      terminal pyroglutamate, C-terminal lysine truncation, and Fc glycosylation. The
      results show that various degrees and/or types of N-terminal pyroglutamate
      formation and C-terminal lysine (Lys) cleavage account for the majority of charge
      heterogeneity; and the charge variants showed Fc glycosylation patterns in
      relation to their terminal modifications. The amount of G1F decreased in the
      basic variants, whereas Man5 and G0F-GN increased. The complement-dependent
      cytotoxicity (CDC) activity of purified charge variants also suggested the
      potential impact of the charge differences on the glycosylation profile. 

PMID- 24287082
TI  - A protocol proposition of cell therapy for the treatment of chronic obstructive
      pulmonary disease.
AB  - The main feature of pulmonary emphysema is airflow obstruction resulting from the
      destruction of the alveolar walls distal to the terminal bronchioles. Existing
      clinical approaches have improved and extended the quality of life of emphysema
      patients. However, no treatment currently exists that can change the disease
      course and cure the patient. The different therapeutic approaches that are
      available aim to increase survival and/or enhance the quality of life of
      emphysema patients. In this context, cell therapy is a promising therapeutic
      approach with great potential for degenerative pulmonary diseases. In this
      protocol proposition, all patients will be submitted to laboratory tests, such as
      evaluation of heart and lung function and routine examinations. Stem cells will
      be harvested by means of 10 punctures on each anterior iliac crest, collecting a
      total volume of 200mL bone marrow. After preparation, separation, counting and
      labeling (optional) of the mononuclear cells, the patients will receive an
      intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This
      article proposes a rational and safe clinical cellular therapy protocol which has
      the potential for developing new projects and can serve as a methodological
      reference for formulating clinical application protocols related to the use of
      cellular therapy in COPD. This study protocol was submitted and approved by the
      Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration
      number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). 

PMID- 24287083
TI  - [Anesthetic management of a patient with mitochondrial encephalomyopathy
      underwent emergency open cholecystectomy].

PMID- 24287074
TI  - Sex differences in circadian timing systems: implications for disease.
AB  - Virtually every eukaryotic cell has an endogenous circadian clock and a
      biological sex. These cell-based clocks have been conceptualized as oscillators
      whose phase can be reset by internal signals such as hormones, and external cues
      such as light. The present review highlights the inter-relationship between
      circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus
      (SCN) serves as a master clock synchronizing the phase of clocks throughout the
      body. Gonadal steroid receptors are expressed in almost every site that receives
      direct SCN input. Here we review sex differences in the circadian timing system
      in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal
      pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which
      disruption of circadian rhythms within these systems differs in the sexes and is
      associated with dysfunction and disease. Understanding sex differentiated
      circadian timing systems can lead to improved treatment strategies for these
      conditions. 

PMID- 24287084
TI  - [Unexpected atrial fibrillation when monitoring in operating room. Case of the
      trimester].
AB  - A real case reported to the SENSAR database of incidents is presented. In a
      patient scheduled for nose fracture repair surgery an unexpected atrial
      fibrillation was found when monitored in the operating room. The operation was
      not delayed. After induction of general anaesthesia heart rate suddenly increased
      and hemodinamic situation was impaired. Cardioversion was required. Two electric
      countershocks were given but sinus rhythm was not restored. Heart rate was
      controlled with amiodarone infusion. Optimal defibrillation characteristics are
      described in these cases. Increased risk of thromboembolism (1-2%) following
      cardioversion is present even if atrial thrombi are ruled out. The mainstay
      therapies of are rhythm and rate control and prevention of thromboembolic
      complications. We describe recommendations on the management of these critical
      situations with emphasis in learning through the creation of protocols and
      training practice in simulation.

PMID- 24287085
TI  - Associations of multiple metals with kidney outcomes in lead workers: author
      response.

PMID- 24287086
TI  - Personal and workplace risk factors for carpal tunnel syndrome.

PMID- 24287087
TI  - Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion.
AB  - BACKGROUND AND PURPOSE: Basilar artery occlusion remains one of the most
      devastating subtypes of ischemic stroke. The prognosis is poor if early
      recanalization is not achieved. The purpose of this study was to evaluate the
      safety and technical feasibility of self-expanding retrievable stents in the
      endovascular treatment of acute basilar artery occlusion. MATERIALS AND METHODS:
      Twenty-four patients with acute basilar artery occlusion were treated with
      Solitaire FR or Revive SE devices between December 2009 and May 2012. Additional
      treatment included intravenous and/or intra-arterial thrombolysis (21/24) and
      percutaneous transluminal angioplasty/permanent stent placement (7/24).
      Recanalization was assessed by means of the TICI score. Clinical outcome was
      determined at discharge (NIHSS), and at 3 months (mRS). RESULTS: Median NIHSS
      score on admission was 24; median duration of symptoms was 254 minutes.
      Successful recanalization (TICI 2b +3) by thrombectomy only was achieved in 18
      patients (75%). Intracranial stent deployment after thrombectomy caused by
      underlying atherosclerotic stenosis was performed in 7 patients. If these
      patients with intracranial stent placement are included, successful
      recanalization was achieved in 21 of 24 patients (87.5%). NIHSS improvement >=10
      points was reached in 54% of patients (n = 13/24). Mortality during the first 3
      months was 29% (7/24). After 3 months, 8 patients (33%) had a favorable clinical
      outcome (mRS 0-2). CONCLUSIONS: In our series, application of self-expanding
      retrievable stents in acute basilar artery occlusion resulted in a high
      recanalization rate without procedural complications and good clinical outcome in
      one-third of patients.

PMID- 24287089
TI  - Andreas Vesalius and Thomas Willis: their anatomic brain illustrations and
      illustrators.
AB  - The brain illustrations of Vesalius and Willis were the first in anatomic history
      with pictorial accuracy. Their illustrations, illustrators, and methods are
      discussed. Woodcut blocks were used for the prints of figures in the Vesalian
      anatomy. Figures of the brain appear to be done after external fixation in the
      work of Willis.

PMID- 24287088
TI  - Reproducibility of cerebrospinal venous blood flow and vessel anatomy with the
      use of phase contrast-vastly undersampled isotropic projection reconstruction and
      contrast-enhanced MRA.
AB  - BACKGROUND AND PURPOSE: The chronic cerebrospinal venous insufficiency hypothesis
      raises interest in cerebrospinal venous blood flow imaging, which is more complex
      and less established than in arteries. For accurate assessment of venous flow in
      chronic cerebrospinal venous insufficiency diagnosis and research, we must
      account for physiologic changes in flow patterns. This study examines day-to-day
      flow variability in cerebrospinal veins by use of 4D MR flow and contrast
      enhanced MRA under typical, uncontrolled conditions in healthy individuals.
      MATERIALS AND METHODS: Ten healthy volunteers were scanned in a test-retest
      fashion by use of a 4D flow MR imaging technique and contrast-enhanced MRA. Flow
      parameters obtained from phase contrast-vastly undersampled isotropic projection
      reconstruction and contrast-enhanced MRA scoring measurements in the head, neck,
      and chest veins were analyzed for internal consistency and interscan
      reproducibility. RESULTS: Internal consistency was satisfied at the torcular
      herophili, with an input-output difference of 2.2%. Percentages of variations in
      flow were 20.3%, internal jugular vein; 20.4%, azygos vein; 6.8%, transverse
      sinus; and 5.1%, common carotid artery. Retrograde flow was found in the lower
      internal jugular vein (4.8%) and azygos vein (7.2%). Contrast-enhanced MRA
      interscan kappa values for the internal jugular vein (left: 0.474, right: 0.366)
      and azygos vein (-0.053) showed poor interscan agreement. CONCLUSIONS: Phase
      contrast-vastly undersampled isotropic projection reconstruction blood flow
      measurements are reliable and highly reproducible in intracranial veins and in
      the common carotid artery but not in veins of the neck (internal jugular vein)
      and chest (azygos vein) because of normal physiologic variation. Retrograde flow
      normally may be observed in the lower internal jugular vein and azygos vein. Low
      interrater agreement in contrast-enhanced MRA scans was observed. These findings
      have important implications for imaging diagnosis and experimental research of
      chronic cerebrospinal venous insufficiency.

PMID- 24287090
TI  - Endovascular treatment of anterior communicating artery aneurysms: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Endovascular therapy has become an acceptable alternative
      to traditional clipping for the management of intracranial aneurysms. However, a
      limited number of studies have examined outcomes and complications specific to
      embolization of anterior communicating artery aneurysms. MATERIALS AND METHODS: A
      systematic review of the literature was conducted with the use of multiple data
      bases to identify reports on endovascular treatment of anterior communicating
      artery aneurysms between 1994 and 2012. Angiographic results, clinical outcomes,
      and complication rates were pooled across studies by using random-effects meta
      analysis with subgroup analysis of outcomes by rupture status and time trend
      stratification. RESULTS: Fourteen studies, consisting of 1552 treated anterior
      communicating artery aneurysms, were included in this meta-analysis. The rate of
      immediate and long-term complete and near-complete angiographic occlusion was 88%
      (95% CI = 81-93%) and 85% (95% CI = 78-90%), respectively. Intraprocedural
      rupture rate was 4% (95% CI = 3-6%). The re-bleeding rate was 2% (95% CI = 1-4%)
      and the retreatment rate was 7% (95% CI = 5-12%). Morbidity or mortality caused
      by perioperative stroke occurred at a 3% (95% CI = 2-6%) rate. Overall procedure
      related morbidity and mortality were 6% (95% CI = 4-8%) and 3% (95% CI = 2-4%),
      respectively. Outcomes did not differ between ruptured and unruptured aneurysms,
      nor did outcomes change over time, though these latter subanalyses were
      relatively underpowered. CONCLUSIONS: Endovascular therapy for anterior
      communicating artery aneurysms is associated with a high rate of complete
      angiographic occlusion. However, the procedure-related permanent morbidity and
      mortality are not negligible for aneurysms in this location.

PMID- 24287091
TI  - Computational hemodynamics analysis of intracranial aneurysms treated with flow
      diverters: correlation with clinical outcomes.
AB  - BACKGROUND AND PURPOSE: Recent studies have shown promising results regarding
      intracranial aneurysms treated with flow diverters. However, these have had
      adverse effects, including delayed aneurysm occlusion, posttreatment symptoms,
      and rupture. The hemodynamic profiles of aneurysms treated with flow diverters
      were analyzed to determine the ones associated with successful and failed
      treatments. MATERIALS AND METHODS: Patient-specific computational fluid dynamics
      were used to simulate hemodynamic profiles, including the presence of jet flow,
      energy loss, volume flow, and wall shear stress in 4 successful occlusions of
      aneurysms and 4 failed cases after flow-diverter deployment. In these 4 failed
      cases, hemodynamic profiles were examined again after a hypothetic second
      intervention. This involved replacing the failed flow diverter with a hypothetic
      optimally deployed flow diverter or simulated placement of a second flow diverter
      within the first (double hypothetic optimally deployed). RESULTS: Where
      successful occlusions were achieved, a marked obliteration of jet flow was
      observed. Flow entering the aneurysm sac was diverted via the center of the flow
      diverter and joined smoothly with the continuation of flow leaving the aneurysm
      sac into the parent arteries. These observations were supplemented by a reduction
      in the other hemodynamic profiles. Aneurysm neck geometry might influence the
      efficacy of the flow diverter. CONCLUSIONS: Hemodynamic indices, as calculated by
      using computational fluid dynamics techniques, have close correlation with flow
      diverter treatment outcome. Computational fluid dynamics could be potentially
      useful as a planning tool for neurointerventionists by simulating an optimized
      flow-diverter deployment strategy before the procedure and evaluating
      posttreatment outcome.

PMID- 24287092
TI  - Transverse sinus stenting for pseudotumor cerebri: a cost comparison with CSF
      shunting.
AB  - BACKGROUND AND PURPOSE: Transverse sinus venous stent placement has been shown to
      lower intracranial pressure in patients with venogenic pseudotumor cerebri and to
      reverse, or at least stabilize, its symptoms and signs. There have been no
      studies comparing the cost of venous stenting with the time-honored treatment for
      pseudotumor cerebri-CSF shunting. The purpose of this study was to compare the
      cost of trasverse sinus stenting versus CSF shunting for the treatment of
      pseudotumor cerebri. MATERIALS AND METHODS: This work was a retrospective cost
      analysis of individual resource use in 86 adults who were stented for pseudotumor
      cerebri during a 12-year period compared with resource use in 110 children who
      were shunted for hydrocephalus during a 3-year period. RESULTS: There was no
      significant difference between the cost of inserting an initial venous stent
      ($13,863 +/- 4890) versus inserting an initial CSF shunt ($15,797 +/- 5442) (P =
      .6337) or between inserting an additional venous stent ($9421 +/- 69) versus
      revising a CSF shunt ($10,470 +/- 1245) (P = .4996). There were far fewer
      additional venous stent insertions per patient than there were subsequent CSF
      shunt revisions; 87% of stents placed required just 1 stent procedure, whereas
      only 45% of shunts required 1 shunt procedure. The main cause of the cost
      difference was the need for repeated revisions of the shunts, especially when
      they became infected-24 instances of a total 143 shunt procedures (16.8%) at an
      average cost of $84,729, approximately 5 times the cost of an initial shunt
      insertion. CONCLUSIONS: Venous stenting costs significantly less per 100
      procedures than does CSF shunting, due largely to the high cost of treating shunt
      infections and the need for repeated shunt revisions.

PMID- 24287093
TI  - Hyperattenuated intracerebral lesions after mechanical recanalization in acute
      stroke: contrast and compare.

PMID- 24287095
TI  - Can we perform spinal 1H-MR spectroscopy in daily clinical practice?

PMID- 24287094
TI  - Characterization of peripheral nerve sheath tumors with 3T proton MR
      spectroscopy.
AB  - BACKGROUND AND PURPOSE: The characterization of peripheral nerve sheath tumors is
      challenging. The purpose here was to investigate the diagnostic value of
      quantitative proton MR spectroscopy at 3T for the characterization of peripheral
      nerve sheath tumors as benign or malignant, compared with PET. MATERIALS AND
      METHODS: Twenty participants with 24 peripheral nerve sheath tumors underwent MR
      spectroscopy by use of a point-resolved sequence (TE, 135 ms). Six voxels were
      placed in 4 histologically proven malignant peripheral nerve sheath tumors and 22
      voxels in 20 benign peripheral nerve sheath tumors (9 histologically proven, 11
      with documented stability). The presence or absence of a trimethylamine signal
      was evaluated, the trimethylamine concentration estimated by use of phantom
      replacement methodology, and the trimethylamine fraction relative to Cr measured.
      MR spectroscopy results for benign and malignant peripheral nerve sheath tumors
      were compared by use of a Mann-Whitney test, and concordance or discordance with
      PET findings was recorded. RESULTS: In all malignant tumors and in 9 of 18 benign
      peripheral nerve sheath tumors, a trimethylamine peak was detected, offering the
      presence of trimethylamine as a sensitive (100%), but not specific (50%), marker
      of malignant disease. Trimethylamine concentrations (2.2 +/- 2.8 vs 6.6 +/- 5.8
      institutional units; P < .049) and the trimethylamine fraction (27 +/- 42 vs 88
      +/- 22%; P < .012) were lower in benign than malignant peripheral nerve sheath
      tumors. A trimethylamine fraction threshold of 50% resulted in 100% sensitivity
      (95% CI, 58.0%-100%) and 72.2% (95% CI, 59.5%-75%) specificity for distinguishing
      benign from malignant disease. MR spectroscopy and PET results were concordant in
      12 of 16 cases, (2 false-positive results for MR spectroscopy and PET each).
      CONCLUSIONS: Quantitative measurement of trimethylamine concentration by use of
      MR spectroscopy is feasible in peripheral nerve sheath tumors and shows promise
      as a method for the differentiation of benign and malignant lesions.
      Trimethylamine presence within a peripheral nerve sheath tumor is a sensitive
      marker of malignant disease, but quantitative measurement of trimethylamine
      content is required to improve specificity.

PMID- 24287096
TI  - Est modus in rebus.

PMID- 24287097
TI  - Molecular dating, evolutionary rates, and the age of the grasses.
AB  - Many questions in evolutionary biology require an estimate of divergence times
      but, for groups with a sparse fossil record, such estimates rely heavily on
      molecular dating methods. The accuracy of these methods depends on both an
      adequate underlying model and the appropriate implementation of fossil evidence
      as calibration points. We explore the effect of these in Poaceae (grasses), a
      diverse plant lineage with a very limited fossil record, focusing particularly on
      dating the early divergences in the group. We show that molecular dating based on
      a data set of plastid markers is strongly dependent on the model assumptions. In
      particular, an acceleration of evolutionary rates at the base of Poaceae followed
      by a deceleration in the descendants strongly biases methods that assume an
      autocorrelation of rates. This problem can be circumvented by using markers that
      have lower rate variation, and we show that phylogenetic markers extracted from
      complete nuclear genomes can be a useful complement to the more commonly used
      plastid markers. However, estimates of divergence times remain strongly affected
      by different implementations of fossil calibration points. Analyses calibrated
      with only macrofossils lead to estimates for the age of core Poaceae ~51-55 Ma,
      but the inclusion of microfossil evidence pushes this age to 74-82 Ma and leads
      to lower estimated evolutionary rates in grasses. These results emphasize the
      importance of considering markers from multiple genomes and alternative fossil
      placements when addressing evolutionary issues that depend on ages estimated for
      important groups. 

PMID- 24287098
TI  - The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of
      the offspring in a murine model of preeclampsia.
AB  - Animal and human studies show that in-utero exposure to preeclampsia alters fetal
      programming and results in long-term adverse cardiovascular outcomes in the
      offspring. Human epidemiologic data also suggest that offspring born to
      preeclamptic mothers are also at risk of adverse long term neurodevelopmental
      outcomes. Pravastatin, a hydrophilic lipid-lowering drug with pleiotropic
      properties, was found to prevent the altered cardiovascular phenotype of
      preeclampsia and restore fetal growth in animal models, providing biological
      plausibility for its use as a preventive agent for preeclampsia. In this study,
      we used a murine model of preeclampsia based on adenovirus over-expression of the
      anti-angiogenic factor soluble Fms-like tyrosine kinase 1, and demonstrated that
      adult offspring born to preeclamptic dams perform poorly on assays testing
      vestibular function, balance, and coordination, and that prenatal pravastatin
      treatment prevents impairment of fetal programming. 

PMID- 24287099
TI  - Can music therapy alleviate psychological, cognitive, and behavioral impairment
      in epilepsy?

PMID- 24287100
TI  - Aerobic exercise during pregnancy influences infant heart rate variability at one
      month of age.
AB  - BACKGROUND: Previously, we reported that regular maternal aerobic exercise during
      pregnancy was associated with lower fetal heart rate (HR) and higher heart rate
      variability (HRV) at 36weeks gestation. We now report the effect of maternal
      exercise on infant HR and HRV in subjects who remained active in the study at the
      one-month follow up visit. AIMS: We aimed to determine whether differences in
      fetal cardiac autonomic control related to maternal physical activity were an in
      utero phenomenon or would persist 1month after birth. STUDY DESIGN:
      Magnetocardiograms (MCGs) of infants born to regularly exercising (>=30min of
      aerobic activity, 3 times per week; N=16) and non-exercising (N=27) pregnant
      women were recorded using a fetal biomagnetometer. Normal R-peaks were marked to
      derive infant HR and HRV in time and frequency domains, including the root mean
      square of successive differences (RMSSD), the standard deviation of normal-to
      normal interbeat intervals (SDNN), and power in the low frequency (LF) and high
      frequency (HF) bands. Group differences were examined with Student's t-tests.
      RESULTS: Infants born to exercising women had significantly higher RMSSD
      (P=0.010), LF power (P=0.002), and HF power (P=0.004) than those born to women
      who did not engage in regular physical activity while pregnant. CONCLUSION:
      Infants born to women who participated in regular physical activity during
      pregnancy continued to have higher HRV in the infant period. This suggests that
      the developing cardiac autonomic nervous system is sensitive to the effects of
      maternal physical activity and is a target for fetal programming.

PMID- 24287101
TI  - Reversal of multidrug resistance phenotype in human breast cancer cells using
      doxorubicin-liposome-microbubble complexes assisted by ultrasound.
AB  - The circumvention of multidrug resistance (MDR) plays a critically important role
      in the success of chemotherapy. The aim of this work is to investigate the
      effectiveness and possible mechanisms of the reversal of MDR phenotype in human
      breast cancer cells by using doxorubicin-liposome-microbubble complexes (DLMC)
      assisted by ultrasound (US). DLMC is fabricated through conjugating doxorubicin
      (DOX)-liposome (DL) to the surface of microbubbles (MBs) via the biotin-avidin
      linkage. The resulting drug-loaded complexes are then characterized and incubated
      with MCF-7/ADR human breast cancer cells and followed by US exposure. Our results
      show the more rapid cellular uptake, evident enhancement of nuclear accumulation
      and less drug efflux in the resistant cells treated by DLMC+US than those treated
      by DL, DL+verapamil under the same US treatment or DLMC without US. The enhanced
      drug delivery and cellular uptake also associated with the increase of
      cytotoxicity against MCF-7/ADR cells, lower MCF-7/ADR cell viability and higher
      apoptotic cells. Mechanism investigations further disclose a significant increase
      of reactive oxygen species (ROS) level, enhanced DNA damage and obvious reduction
      of P-glycoprotein expression in the resistant cells treated with DLMC+US compared
      with the control cases of cells treated by DLMC, DL+US or DL+verapamil+US. In
      conclusion, our study demonstrates that DLMC in combination with US may provide
      an effective delivery of drug to sensitize cells to circumvent MDR and to enhance
      the therapeutic index of the chemotherapy. 

PMID- 24287102
TI  - Water soluble molybdenocene complexes: synthesis, cytotoxic activity and binding
      studies to ubiquitin by fluorescence spectroscopy, circular dichroism and
      molecular modeling.
AB  - Four new molybdenocene complexes, Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l
      ascorbato), [Cp2Mo(ethyl maltolato)]Cl and Cp2Mo((2S)-2-amino-3-methyl-3-thiolato
      butanoato), were synthesized and structurally characterized by standard
      analytical methods. The cytotoxicity of these complexes was assessed on colon HT
      29 and breast MCF-7 cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. A higher cytotoxic activity was shown by
      all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex. The complexes
      Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato) and [Cp2Mo(ethyl
      maltolato)]Cl displayed a stronger cytotoxic activity on colon cancer HT-29 cell
      line, over the molybdenocene dichloride (Cp2MoCl2). In contrast, Cp2Mo((2S)-2
      amino-3-methyl-3-thiolato-butanoato) exhibited proliferative properties on this
      cell line. Ubiquitin (Ub)-molybdenocene interactions were investigated using
      cyclic voltammetry, fluorescence quenching spectroscopy, circular dichroism (CD)
      and molecular modeling. The thermodynamic parameters (DeltaH and DeltaS) obtained
      using fluorescence quenching spectra and van't Hoff plot indicate the Ub
      molybdenocene interactions are mainly hydrophobic. The CD data also support
      hydrophobic interactions with conformational changes in the Ub protein. Docking
      studies using molecular modeling revealed the amino acids involved in the Ub
      molybdenocene interactions and corroborated the hydrophobic nature of the binding
      combined with hydrogen bonding. 

PMID- 24287103
TI  - Photoactive metal carbonyl complexes as potential agents for targeted CO
      delivery.
AB  - The surprising discovery of carbon monoxide (CO) as a signaling molecule in
      mammalian physiology has recently raised interest in this toxic gas among
      researchers in biochemical and pharmaceutical community. CO is endogenously
      produced mainly from catabolism of heme by the enzyme heme oxygenase (HO) and
      participates in a myriad of anti-inflammatory, anti-proliferative, and
      vasoregulatory pathways. In animal models, low doses of CO have exhibited
      beneficial effects in suppression of organ graft rejection and safeguarding the
      heart during reperfusion after cardiopulmonary bypass surgery. The salutary
      effects of CO have naturally drawn attention of the pharmaceutical industry for
      its use as a cytoprotective agent. Safety-related concerns of the use of this
      noxious gas have prompted research in the area of syntheses of CO-releasing
      molecules (CORMs) and to date, several metal carbonyls (metal complexes of CO)
      have been employed as CORMs in promoting prolonged (and safe) delivery of low
      doses of CO to cellular targets. Because many carbonyl complexes release CO upon
      illumination, investigators have recently began to explore the possibility of
      "controlled CO delivery" through the use of light. During the past few years, a
      number of photoactive CORMs or "photoCORMs" have been synthesized that release CO
      upon illumination with UV or visible light. The utility of these photoCORMs in CO
      delivery has also been confirmed. Novel design principles for isolation of
      photoCORMs have started to appear in recent reports. Scrutiny of the literature
      reveals the emergence of a new exciting area of drug development in such efforts.
      The potential of photoCORMs as CO-donating pharmaceuticals along with a brief
      overview of the physiological roles of CO is presented in this review. 

PMID- 24287104
TI  - Phylogeography and evolutionary history of rodent-borne hantaviruses.
AB  - Hantavirus (Family Bunyaviridae) are mostly associated to rodents and transmitted
      to man by inhalation of aerosolized infected excreta of these animals. The human
      infection by hantaviruses can lead to severe diseases such as hemorrhagic fever
      with renal syndrome (HFRS) in Asia and Europe, and pulmonary syndrome (HPS) in
      the Americas. To determine the origin, spreading and evolutionary dynamics of
      rodent-borne hantaviruses, 190 sequences of nucleoprotein (N) of hantaviruses
      identified in 30 countries, from 1985 to 2010, were retrieved from the GenBank
      and analyzed using the BEAST program. Our evolutionary analysis indicates that
      current genetic diversity of N gene of rodent-borne hantaviruses probably was
      originated around 2000 years ago. Hantavirus harbored by Murinae and Arvicolinae
      subfamilies, probably, were originated in Asia 500-700 years ago and later spread
      toward Siberia, Europe, Africa and North America. Hantavirus carried by
      Neotominae subfamily, probably, emerged 500-600 years ago in Central America and
      spread toward North America. Finally, hantaviruses associated to Sigmodontinae
      occurred in Brazil 400 years ago and were, probably, originated from Neotominae
      associated virus from northern South America. These data offer subsidies to
      understand the time-scale and worldwide dissemination dynamics of rodent-borne
      hantaviruses.

PMID- 24287105
TI  - Guest editorial. The role of oxytocin in positive affect and drug-related reward.

PMID- 24287106
TI  - Factors influencing the selection of hydrocodone and oxycodone as primary opioids
      in substance abusers seeking treatment in the United States.
AB  - The purpose of the present study was to identify the factors that influence the
      selection of hydrocodone and oxycodone as primary drugs of abuse in opioid
      dependent subjects (n = 3520) entering one of 160 drug treatment programs around
      the country. Anonymous, self-administered surveys and direct qualitative
      interviews were used to examine the influence of demographic characteristics,
      drug use patterns, and decision-related factors on primary opioid selection. Our
      results showed that oxycodone and hydrocodone were the drugs of choice in 75% of
      all patients. Oxycodone was the choice of significantly more users (44.7%) than
      hydrocodone (29.4%) because the quality of the high was viewed to be much better
      by 54% of the sample, compared to just 20% in hydrocodone users, who cited
      acetaminophen as a deterrent to dose escalation to get high and hence, its low
      euphoric rating. Hydrocodone users were generally risk-averse women, elderly
      people, noninjectors, and those who prefer safer modes of acquisition than
      dealers (ie, doctors, friends, or family members). In contrast, oxycodone was a
      much more attractive euphorigenic agent to risk-tolerant young, male users who
      prefer to inject or snort their drugs to get high and are willing to use more
      aggressive forms of diversion. Prevention and treatment approaches, and pain
      physicians, should benefit from these results because it is clear that not all
      drug abusers share the same characteristics, and the decision to use one drug
      over another is a complex one, which is largely attributable to individual
      differences (eg, personality, gender, age, and other factors).

PMID- 24287108
TI  - Membrane damages under high pressure of human erythrocytes agglutinated by
      concanavalin A.
AB  - Human erythrocytes are agglutinated by lectins such as concanavalin A (Con A).
      The behaviors of agglutinated erythrocytes under pressure are less well
      understood. Here, we report the effects of erythrocyte agglutination on pressure
      induced membrane damages. Small clumps of intact erythrocytes by Con A were
      dissociated by a pressure of 200 MPa. Further, the observation by scanning
      electron microscopy demonstrated the generation of vesicles, fragmented
      particles, and membrane hole. On the other hand, large clumps of trypsin-digested
      erythrocytes by Con A seemed to be stable against 200 MPa. However, the
      erythrocytes dissociated from such pressure-treated clumps by methyl alpha
      mannopyranoside also showed the existence of vesicles and fragmented particles
      except for the membrane hole. Pressure-induced hemolysis was greatly suppressed
      in such large clumps. Similar suppressive effects were observed in erythrocytes
      packed by centrifugation. However, the hemolysis occurred when the erythrocytes
      dissociated from 200 MPa-treated large clumps by methyl alpha-mannopyranoside
      were incubated at 0 degrees C and atmospheric pressure. Pyrene excimer
      fluorescence due to spectrin denaturation was observed in Con A-agglutinated
      ghosts that were exposed to a pressure of 200 MPa. These results suggest that
      upon pressure treatment of tightly agglutinated erythrocytes, the hemolysis is
      greatly suppressed, but membrane damages occur such as spectrin denaturation and
      vesiculation.

PMID- 24287107
TI  - Prevalence and impact of pain among older adults in the United States: findings
      from the 2011 National Health and Aging Trends Study.
AB  - This study sought to determine the prevalence and impact of pain in a nationally
      representative sample of older adults in the United States. Data from the 2011
      National Health and Aging Trends Study were analyzed. In-person interviews were
      conducted in 7601 adults ages >=65 years. The response rate was 71.0% and all
      analyses were weighted to account for the sampling design. The overall prevalence
      of bothersome pain in the last month was 52.9%, afflicting 18.7 million older
      adults in the United States. Pain did not vary across age groups (P = 0.21), and
      this pattern remained unchanged when accounting for cognitive performance,
      dementia, proxy responses, and residential care living status. Pain prevalence
      was higher in women and in older adults with obesity, musculoskeletal conditions,
      and depressive symptoms (P < 0.001). The majority (74.9%) of older adults with
      pain endorsed multiple sites of pain. Several measures of physical capacity,
      including grip strength and lower-extremity physical performance, were associated
      with pain and multisite pain. For example, self-reported inability to walk 3
      blocks was 72% higher in participants with than without pain (adjusted prevalence
      ratio 1.72 [95% confidence interval 1.56-1.90]). Participants with 1, 2, 3, and
      >=4 sites of pain had gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per
      second slower, respectively, than older adults without pain, adjusting for
      disease burden and other potential confounders (P < 0.001). In summary,
      bothersome pain in the last month was reported by half of the older adult
      population of the United States in 2011 and was strongly associated with
      decreased physical function.

PMID- 24287109
TI  - Electropolymerization of curcumin on glassy carbon electrode and its
      electrocatalytic application for the voltammetric determination of epinephrine
      and p-acetoaminophenol.
AB  - Here in, we report the simultaneous voltammetric determination of epinephrine
      (EP) and p-acetoaminophenol (AP) on a poly curcumin (1,7 Bis ((4-hydroxy-3
      methoxyphenyl)-1,6-heptadiene-3,5 dione), poly CM) modified glassy carbon
      electrode (GCE) for the first time. The CM was polymerized on to the GCE surface
      by simple electro polymerization process. A low peak to peak (DeltaEp) separation
      of 60 mV was observed, indicating fast electron transfer between poly CM and the
      electrode surface. The electrochemical measurements and surface morphology of the
      as prepared poly CM film modified electrode were studied using cyclic voltammetry
      (CV), and field emission scanning electron microscopy (SEM), respectively.
      Moreover, poly CM modified GCE exhibits enhanced electro catalytic activity
      toward EP and AP in the linear range of 4.97-230.76 MUM and 0.99-230.76 MUM and
      with very low detection limit (LOD) of 0.05 MUM and 0.1 MUM. The sensitivity is
      0.621 and 0.303 MUAMUM(-1)cm(2) for EP and AP, respectively. The practical
      feasibility of the proposed poly CM/GCE was evaluated in adrenaline injection (1
      mg mL(-1)) solutions and paracetamol tablets for the simultaneous determination
      of EP and AP. We found maximum recovery of 99.2% for adrenaline injection and
      97.4% for paracetamol tablets. Finally the modified electrode exhibit excellent
      repeatability, reproducibility and stability for the selective and simultaneous
      determination of EP and AP.

PMID- 24287110
TI  - Preparation and characterization of PEG-Mentha oil nanoparticles for housefly
      control.
AB  - Nanoparticles of Mentha * piperita essential oil were prepared by melt-dispersion
      method. The nanoparticles prepared at varying oil doses (5-10%, w/v) showed an
      encapsulation efficiency of 78.2-83.4%, while the oil load was observed to range
      between 3.64 and 7.46%. The average particle size of the nanoparticles varied
      between 226 and 331 nm, while polydispersity index showed variation between 0.547
      and 1.000. DSC analysis indicated endothermic reaction during formation of
      nanoparticles, while a 2-term exponential kinetic model was followed during oil
      release. Nanoparticles showed considerable mortality against housefly larvae in
      lab (100%) as well as simulated field condition after first week (93%) and 6th
      week (57%) of application. This was the first study utilizing controlled release
      property of nanoparticles to formulate a cost effective product for breeding site
      application against housefly.

PMID- 24287111
TI  - Pro-apoptotic activity of new analog of anthracyclines--WP 631 in advanced
      ovarian cancer cell line.
AB  - In this work we investigated the mode of cell death induced by WP 631, a novel
      anthracycline antibiotic, in the ovarian cancer cell line (OV-90) derived from
      the malignant ascites of a patient diagnosed with advanced disease. The effects
      were compared with those of doxorubicin (DOX), a first generation anthracycline.
      The ability of WP 631 to induce apoptosis and necrosis was examined by double
      staining with Annexin V and propidium iodide, measurements of the level of
      intracellular calcium ions and cytochrome c, PARP cleavage. We also investigated
      the possible involvement of the caspases activation, DNA degradation (comet
      assay) and intracellular reactive oxygen species (ROS) production in the
      development of the apoptotic events and their significance for drug efficiency.
      The results obtained clearly demonstrate that antiproliferative capacity of WP
      631 in tested cell line was a few times greater than that of DOX. Furthermore,
      ovarian cancer cells treated with WP 631 showed a higher mean level of basal DNA
      damage in comparison to DOX. In conclusion, WP 631 is able to induce caspase -
      dependent apoptosis in human ovarian cancer cells. Obtained results suggested
      that WP 631 may be a candidate for further evaluation as chemotherapeutic agents
      for human cancers.

PMID- 24287112
TI  - In vitro evaluation of cell death induced by cadmium, lead and their binary
      mixtures on erythrocytes of Common buzzard (Buteo buteo).
AB  - Cadmium and lead are persistent and ubiquitous metals that can cause several
      deleterious effects in living beings. Apoptosis and necrosis are two types of
      cell death that can be found after in vivo and in vitro exposure to these metals.
      In this study, isolated red blood cells from living captive Common buzzard (Buteo
      buteo) were exposed in vitro to different concentrations of lead, cadmium, and
      the mixture lead-cadmium in a proportion of 1:10 (similar to that found in
      previous field studies). Data obtained from dose-response curves were used to
      evaluate the interactive effects of metal mixtures on cell viability. In general,
      except for the exposure to NOEC, additivity was the most frequently observed
      response. As described in human, after in vitro exposure, lead was highly
      accumulated in buzzard erythrocytes, while cadmium accumulation was scarce.
      Finally, the type of cell death (apoptosis or necrosis) induced by the exposure
      to different concentrations of these heavy metals and their mixtures was
      evaluated in the red blood cells. Apoptosis was found to be the main type of cell
      death observed after cadmium and/or lead exposure. However, this exposure caused
      an increase in lysis or necrosis, especially if red blood cells were exposed to
      high doses.

PMID- 24287113
TI  - The antioxidants, vitamin A and E but not vitamin C and melatonin enhance the
      proapoptotic effects of irinotecan in cancer cells in vitro.
AB  - Irinotecan is one of the camptothecin analog which has been shown to have a broad
      spectrum of antitumor activities against various malignancies. The aim of this
      study was to evaluate the effect of vitamin A, C, E and melatonin on proapoptotic
      activity of irinotecan in human cancer cells in vitro. We observed that
      irinotecan induced apoptosis in all types of analyzed cell lines when used as a
      single agent. Combination of selected antioxidants with various doses of
      irinotecan (7.5-60MUM) resulted in significant increase in apoptotic cell death
      in A549 and HT29 cancer cell lines. The highest killing efficiency was observed
      after co-incubation of the cells with irinotecan and vitamin A (10MUM), or
      vitamin E (25MUM), respectively. The addition of vitamin C and melatonin to
      irinotecan treatment did not promote increase in killing of cancer cells. Our
      results indicate that some antioxidants can enhance the proapoptoic activity
      (properties) of irinotecan in human cancer cells in vitro. These findings may be
      supportive for the optimization of therapeutic efficacy of irinotecan treatment.

PMID- 24287114
TI  - [Trusted person and living will: information and implementation defect].
AB  - PURPOSE: The French law allows the persons of age to appoint a trusted person and
      to draft advance directives in case they are one day in a condition that prevents
      them from expressing their will regarding their health care. Our study objective
      was to assess patients' and relatives' knowledge and collecting their opinion
      regarding these means of expression of their will. METHODS: An anonymous survey
      by self-administered questionnaire was conducted in the admission offices of the
      University Hospital of Nancy in April 2011. The questions focused on trusted
      person and anticipated directives. RESULTS: We collected 367 answers, 61.8% of
      which were females. Average age of respondents was 48.7 years old (standard
      deviation: 15.6). Three fourths of respondents were informed of their possibility
      to appoint a trusted person and were able to establish the difference between a
      trusted person and a contact person. Respondents mainly chose their spouse (52%).
      They thought that the trusted person's opinion takes precedence over the family's
      or relatives' one (64.7%), given that this opinion is based on indications
      previously provided by the patient (74.8%). The majority of people surveyed were
      ignorant of the possibility to draft advance directives but were glad of it
      (57.5%). They would include herein their refusal of unreasonable obstinacy
      (75.8%), their wishes to withhold/withdraw of some treatments, to stop active
      treatments in case of high odds of chronic coma or vegetative state (52.8%) or
      their will to donate organ after death (50.6%). More than three fourths of the
      patients wished to include these informations on their health care card chip.
      CONCLUSION: Legal means of expression of the patient's wishes and are not
      systematically known by the population. The possibility to appoint a trusted
      person is much more known than that to draft advance directives. After the
      release in December 2012 of the Sicard report regarding the end of life in
      France, an important information campaign of the general public remains to be
      undertaken.

PMID- 24287115
TI  - Lesional-targeting of neuroprotection to the inflammatory penumbra in
      experimental multiple sclerosis.
AB  - Progressive multiple sclerosis is associated with metabolic failure of the axon
      and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel
      blockade causes side effects that can limit its use for neuroprotection in
      multiple sclerosis. Through selective targeting of drugs to lesions we aimed to
      improve the potential therapeutic window for treatment. This was assessed in the
      relapsing-progressive experimental autoimmune encephalomyelitis ABH mouse model
      of multiple sclerosis using conventional sodium channel blockers and a novel
      central nervous system-excluded sodium channel blocker (CFM6104) that was
      synthesized with properties that selectively target the inflammatory penumbra in
      experimental autoimmune encephalomyelitis lesions. Carbamazepine and
      oxcarbazepine were not immunosuppressive in lymphocyte-driven autoimmunity, but
      slowed the accumulation of disability in experimental autoimmune
      encephalomyelitis when administered during periods of the inflammatory penumbra
      after active lesion formation, and was shown to limit the development of
      neurodegeneration during optic neuritis in myelin-specific T cell receptor
      transgenic mice. CFM6104 was shown to be a state-selective, sodium channel
      blocker and a fluorescent p-glycoprotein substrate that was traceable. This
      compound was >90% excluded from the central nervous system in normal mice, but
      entered the central nervous system during the inflammatory phase in experimental
      autoimmune encephalomyelitis mice. This occurs after the focal and selective
      downregulation of endothelial p-glycoprotein at the blood-brain barrier that
      occurs in both experimental autoimmune encephalomyelitis and multiple sclerosis
      lesions. CFM6104 significantly slowed down the accumulation of disability and
      nerve loss in experimental autoimmune encephalomyelitis. Therapeutic-targeting of
      drugs to lesions may reduce the potential side effect profile of neuroprotective
      agents that can influence neurotransmission. This class of agents inhibit
      microglial activity and neural sodium loading, which are both thought to
      contribute to progressive neurodegeneration in multiple sclerosis and possibly
      other neurodegenerative diseases. 

PMID- 24287116
TI  - [Epilepsia and Fahr syndrome revealing pseudohypoparathyroidism].

PMID- 24287117
TI  - Transcatheter therapies for mitral regurgitation: a professional society overview
      from the American College of Cardiology, the American Association for Thoracic
      Surgery, Society for Cardiovascular Angiography and Interventions Foundation, and
      The Society of Thoracic Surgeons.

PMID- 24287118
TI  - Ghrelin protects human umbilical vein endothelial cells against high glucose
      induced apoptosis via mTOR/P70S6K signaling pathway.
AB  - Ghrelin exhibits its biological effect through binding to the growth hormone
      secretagogue 1a receptor (GHS-R1a). Recently, it has been reported that ghrelin
      has an anti-apoptotic effect in several cell types. However, the molecule
      mechanisms underlying the anti-apoptotic effect of ghrelin remain poorly
      understood. In this study, we investigated the intracellular mechanisms
      responsible for anti-apoptotic effect of ghrelin on human umbilical vein
      endothelial cells (HUVEC). Treatment of HUVEC with ghrelin inhibited high glucose
      induced cell apoptosis. Ghrelin stimulated the rapid phosphorylation of mammalian
      target of rapamycin (mTOR), P70S6K and S6. The GHS-R1a-specific antagonist [D
      Lys3]-GHRP-6 abolished the anti-apoptotic effect and inhibited the activation of
      mTOR, P70S6K, S6 induced by ghrelin. Pretreatment of cells with specific
      inhibitor of mTOR blocked the anti-apoptotic effect of ghrelin. In addition,
      ghrelin protected HUVECs against high glucose induced apoptosis by increasing Bcl
      2/Bax ratio. Taken together, our results demonstrate that ghrelin produces a
      protective effect on HUVECs through activating GHS-R1a and mTOR/P70S6K signaling
      pathway mediates the effect of ghrelin. These observations suggest that ghrelin
      may act as a survival factor in preventing HUVECs apoptosis caused by high
      glucose. 

PMID- 24287119
TI  - An integrative meta-analysis of microRNAs in hepatocellular carcinoma.
AB  - We aimed to shed new light on the roles of microRNAs (miRNAs) in liver cancer
      using an integrative in silico bioinformatics analysis. A new protocol for target
      prediction and functional analysis is presented and applied to the 26 highly
      differentially deregulated miRNAs in hepatocellular carcinoma. This framework
      comprises: (1) the overlap of prediction results by four out of five target
      prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB
      (combining machine-learning, alignment, interaction energy and statistical tests
      in order to minimize false positives), (2) evidence from previous microarray
      analysis on the expression of these targets, (3) gene ontology (GO) and pathway
      enrichment analysis of the miRNA targets and their pathways and (4) linking these
      results to oncogenesis and cancer hallmarks. This yielded new insights into the
      roles of miRNAs in cancer hallmarks. Here we presented several key targets and
      hundreds of new targets that are significantly enriched in many new cancer
      related hallmarks. In addition, we also revealed some known and new oncogenic
      pathways for liver cancer. These included the famous MAPK, TGFbeta and cell cycle
      pathways. New insights were also provided into Wnt signaling, prostate cancer,
      axon guidance and oocyte meiosis pathways. These signaling and developmental
      pathways crosstalk to regulate stem cell transformation and implicate a role of
      miRNAs in hepatic stem cell deregulation and cancer development. By analyzing
      their complete interactome, we proposed new categorization for some of these
      miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of
      these miRNAs may be addressed as therapeutic targets or used as therapeutic
      agents. Such dual roles thus expand the view of miRNAs as active maintainers of
      cellular homeostasis. 

PMID- 24287120
TI  - Extensive characterization of human tear fluid collected using different
      techniques unravels the presence of novel lipid amphiphiles.
AB  - The tear film covers the anterior eye and the precise balance of its various
      constituting components is critical for maintaining ocular health. The
      composition of the tear film amphiphilic lipid sublayer, in particular, has
      largely remained a matter of contention due to the limiting concentrations of
      these lipid amphiphiles in tears that render their detection and accurate
      quantitation tedious. Using systematic and sensitive lipidomic approaches, we
      validated different tear collection techniques and report the most comprehensive
      human tear lipidome to date; comprising more than 600 lipid species from 17 major
      lipid classes. Our study confers novel insights to the compositional details of
      the existent tear film model, in particular the disputable amphiphilic lipid
      sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O
      acyl-omega-hydroxyfatty acids, and various sphingolipids and phospholipids in
      tears. The discovery and quantitation of the relative abundance of various tear
      lipid amphiphiles reported herein are expected to have a profound impact on the
      current understanding of the existent human tear film model. 

PMID- 24287121
TI  - Lipidomic analysis of human tear fluid reveals structure-specific lipid
      alterations in dry eye syndrome.
AB  - As current diagnostic markers for dry eye syndrome (DES) are lacking in both
      sensitivity and specificity, a pressing concern exists to develop activity
      markers that closely align with the principal axes of disease progression. In
      this study, a comprehensive lipidomic platform designated for analysis of the
      human tear lipidome was employed to characterize changes in tear lipid
      compositions from a cohort of 93 subjects of different clinical subgroups
      classified based on the presence of dry eye symptoms and signs. Positive
      correlations were observed between the tear levels of cholesteryl sulfates and
      glycosphingolipids with physiological secretion of tears, which indicated the
      possible lacrimal (instead of meibomian) origin of these lipids. Notably, we
      found wax esters of low molecular masses and those containing saturated fatty
      acyl moieties were specifically reduced with disease and significantly correlated
      with various DES clinical parameters such as ocular surface disease index, tear
      breakup time, and Schirmer's I test (i.e., both symptoms and signs). These
      structure-specific changes in tear components with DES could potentially serve as
      unifying indicators of disease symptoms and signs. In addition, the structurally
      specific aberrations in tear lipids reported here were found in patients with or
      without aqueous deficiency, suggesting a common pathology for both DES subtypes. 

PMID- 24287122
TI  - Limited health literacy is a barrier to colorectal cancer screening in England:
      evidence from the English Longitudinal Study of Ageing.
AB  - OBJECTIVE: To determine the association between health literacy and participation
      in publicly available colorectal cancer (CRC) screening in England using data
      from the English Longitudinal Study of Ageing (ELSA). METHODS: ELSA is a
      population-based study of English adults aged >= 50 years. Health literacy,
      participation in the national CRC screening programme, and covariates were
      interview-assessed in 2010-11. All those age-eligible for screening from 2006 to
      11 were included in the present analysis (n=3087). The association between health
      literacy and screening was estimated using multivariable-adjusted logistic
      regression. RESULTS: 73% of participants had adequate health literacy skills.
      Screening uptake was 58% among those with adequate and 48% among those with
      limited health literacy skills. Having adequate health literacy was associated
      with greater odds of CRC screening (multivariable adjusted OR=1.20; 95% CI: 1.00
      1.44), independent of other predictors of screening: age (OR=0.92; 95% CI: 0.91
      0.94 per one year increase), female sex (OR=1.31; 95% CI: 1.11-1.54), and being
      in a higher wealth quintile (OR=1.88; 95% CI: 1.43-2.49). CONCLUSIONS: Limited
      health literacy is a barrier to participation in England's national, publicly
      available CRC screening programme. Interventions should include appropriate
      design of information materials, provision of alternative support, and increased
      one-on-one interaction with health care professionals.

PMID- 24287123
TI  - Association between being employed in a smoke-free workplace and living in a
      smoke-free home: evidence from 15 low and middle income countries.
AB  - OBJECTIVE: To assess whether being employed in a smoke-free workplace is
      associated with living in a smoke-free home in 15 low and middle income countries
      (LMICs). METHODS: Country-specific individual level analyses of cross-sectional
      Global Adult Tobacco Survey data (2008-2011) from 15 LMICs was conducted using
      multiple logistic regression. The dependent variable was living in a smoke-free
      home; the independent variable was being employed in a smoke-free workplace.
      Analyses were adjusted for age, gender, residence, region, education, occupation,
      current smoking, current smokeless tobacco use and number of household members.
      Individual country results were combined in a random effects meta-analysis.
      RESULTS: In each country, the percentage of participants employed in a smoke-free
      workplace who reported living in a smoke-free home was higher than those employed
      in a workplace not smoke-free. The adjusted odds ratios (AORs) of living in a
      smoke-free home among participants employed in a smoke-free workplace (vs. those
      employed where smoking occurred) were statistically significant in 13 of the 15
      countries, ranging from 1.12 [95% CI 0.79-1.58] in Uruguay to 2.29 [1.37-3.83] in
      China. The pooled AOR was 1.61 [1.46-1.79]. CONCLUSION: In LMICs, employment in a
      smoke-free workplace is associated with living in a smoke-free home. Accelerated
      implementation of comprehensive smoke-free policies is likely to result in
      substantial population health benefits in these settings.

PMID- 24287124
TI  - Impact of a web-based intervention supplemented with text messages to improve
      cancer prevention behaviors among adolescents: results from a randomized
      controlled trial.
AB  - OBJECTIVE: To assess the impact of a web-based intervention supplemented with
      text messages to reduce cancer risk linked with smoking, unhealthy diet, alcohol
      consumption, obesity, sedentary lifestyle and sun exposure. METHODS: A total of
      2001 voluntary adolescents from Spain and Mexico were recruited between 2009 and
      2012 and randomly assigned to: one control group and two experimental groups,
      which received exclusively the online intervention (experimental group 1) or the
      intervention supplemented with encouraging text messages (experimental group 2).
      The educational intervention was based on both: successful psychosocial models
      (i.e. A.S.E. and Transtheoretical model) and the school curriculum. RESULTS:
      After a 9-month follow-up, the prevalence of students who did not eat fruit was
      reduced significantly in all groups: experimental group 1 (-62.6%), experimental
      group 2 (-71.5%) and even the control group (-66.8%). Being overweight was only
      reduced in the experimental group 2 (-19.6%). The total cancer behavioral risk
      score, which ranged from 0 to 100 points (highest risk), was significantly
      reduced in the experimental group 1 (-3.5 points) and in the experimental group 2
      (-5.3 points). The text-supplemented online intervention increased the
      probability of improving the post-test total cancer behavioral risk (OR=1.62).
      CONCLUSION: The web-based intervention supplemented with text messages had a
      positive global impact, but it lead to only minimal changes in risky behaviors.
      This intervention appears useful in controlling overweight adolescents. CLINICAL
      TRIAL REGISTRATION NUMBER: ISRCTN27988779.

PMID- 24287125
TI  - Effectiveness of a national cardiovascular disease risk assessment programme: a
      different view.

PMID- 24287126
TI  - Concerns of an itinerant surgeon: results of a Guatemalan surgical aid trip.
AB  - Over the past decade the popularity of foreign medical aid has increased and
      gained notoriety. Operation Walk is a philanthropic organization dedicated to
      improving the ambulatory potential of patients in developing countries by
      providing free surgical treatment for patients who otherwise lack access to care
      of debilitating bone and joint conditions. During Operation Walk Mooresville's
      2013 trip to Guatemala 40 patients prospectively completed a Likert Scale style
      survey. The 63-question survey assessed patient impressions and concerns
      regarding the care they receive as part of itinerant surgical aid trips. Mean
      scores were calculated and then concerns were ranked accordingly. We are aware of
      no other investigation assessing these sorts of patient centered perspectives for
      international surgical aid trips. 

PMID- 24287127
TI  - Imageless computer-assisted versus conventional total hip arthroplasty: one
      surgeon's initial experience.
AB  - Computer-assisted surgery (CAS) systems are advocated to improve component
      positioning in THA, though potential operative risks and costs of CAS have fueled
      debate. The present study examines the radiographic outcomes, operative
      efficiency, cost, and midterm functional outcomes for patients who underwent THA,
      either with CAS or conventional instrumentation. Patient baseline characteristics
      were recorded for 126 lower-extremities in the CAS series, and 215 in the
      conventional series. There was no difference in Harris Hip Score or leg length
      discrepancy between series. Inclination angle, blood loss, and operating room
      times were increased for CAS. These results suggest that CAS confers no advantage
      over conventional methods regarding accuracy of THA component placement, drives
      unreimbursed increases in procedure costs, may expose patients to additional
      operative risk, and produces no functional benefit at midterm follow-up. 

PMID- 24287128
TI  - The association between comorbidity and length of hospital stay and costs in
      total hip arthroplasty patients: a systematic review.
AB  - We performed a systematic review on the relationship between comorbidity and
      length of hospital stay (LOS) and hospital costs (HC). Electronic databases were
      systematically searched for relevant studies, conducting methodological quality
      assessment and best-evidence synthesis: 317 articles were identified, 10 of which
      fit the inclusion criteria; nine studies determined the relationship between
      comorbidity and LOS, with eight reporting a positive correlation; five studies
      were considered to be of high quality, four of which found a positive
      correlation; two studies analyzed the relationship between comorbidity and HC and
      reported significantly higher HC for patients with comorbidities, and were
      considered to be of high quality. In conclusion, there is limited evidence that
      patient comorbidity has a positive correlation with LOS and HC. 

PMID- 24287129
TI  - Rapid relapse in depression following initialization of oral contraception with
      ethinyl estradiol and chlormadinone acetate.
AB  - OBJECTIVE: Female sexual hormones (estrogens and gestagens) may affect
      neurocognitive functioning and mood. Thus, the use of oral hormonal
      contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as
      depression and psychosis. However, the available empiric evidence regarding this
      connection is conflicting, and, moreover, female sex hormones seem to feature
      also mood-stabilizing and antidepressive effects. Hence, individual
      susceptibility factors and preparation-specific pharmacologic properties might
      play a pivotal role in the development of mood disturbances related to OHC.
      Single case reports provide empiric data for further systematic approaches.
      METHODS: A clinical case is presented and discussed. RESULTS: A 36-year-old
      female patient with recurrent major depressive disorder developed rapid relapse
      in depression after initialization of OHC with ethinyl estradiol 30
      MUg/chlormadinone acetate 2 mg. This OHC combination was described to
      particularly feature positive effects on depressive mood. CONCLUSIONS: OHC may
      induce serious mood disturbances and should be administered with care,
      particularly in patients with affective disorders.

PMID- 24287130
TI  - Epileptic seizure presenting as dementia with Lewy bodies.
AB  - Psychotic symptoms and cognitive fluctuation are common manifestations of
      dementia with Lewy bodies (DLB). However, the differentiation of these symptoms
      is difficult because many psychiatric, neurologic, and medical conditions in
      addition to drug effects can mimic DLB in elderly people. We report on an 83-year
      old woman who complained of vivid, recurrent visual hallucinations associated
      with fluctuating cognition. The patient was diagnosed as probable DLB. However,
      laboratory findings were consistent with an epileptic phenomenon and the patient
      improved completely with use of anti-epileptic drugs. This case illustrates the
      fact that epileptic seizure may cause symptoms that mimic DLB, and clinicians
      should consider an epileptic condition as a differential diagnosis for elderly
      patients with psychiatric symptoms and fluctuating cognition. 

PMID- 24287131
TI  - A decade of Clinical Trials.

PMID- 24287132
TI  - Concealment and fabrication: the hidden price of payment for research
      participation?

PMID- 24287133
TI  - Discordant minimum inhibitory concentration analysis: a new path to licensure for
      anti-infective drugs.
AB  - BACKGROUND: Evaluation of anti-infective drugs for licensure often relies on a
      noninferiority (NI) design where new drug B is noninferior to comparator drug A
      if the difference in success rates is reliably not worse than some fixed margin.
      The margin must be based on historical studies that estimate the magnitude of the
      benefit of drug A over placebo. This approach hampers drug development because
      the obligatory evidence for margin determination is often nonexistent. PURPOSE:
      To develop a new method for licensure of anti-infective drugs when there is no
      historical evidence for reliable construction of the NI margin. METHODS: The
      minimum inhibitory concentration (MIC) measures the minimum amount of drug that
      it takes to inhibit growth of bacteria in vitro. Patients who are infected with
      bacteria that have a low MIC to a given drug are expected to have good outcomes
      when treated with that drug. Thus, a differential effect of drug B versus drug A,
      if it exists, is likely to occur in patients whose pathogens have discordant MICs
      (e.g., low MIC for drug B, high MIC for drug A, or vice versa). A new paradigm
      for licensure of anti-infective drugs is proposed where a clinically acceptable
      NI margin is selected and licensure supported if the NI margin is met and B is
      reliably demonstrated superior to A in a subset of patients whose paired MICs
      favor B. The requirement for some evidence of superiority encourages a study that
      is carefully designed and executed. RESULTS: Simulations indicate that the
      approach shows promise in realistic settings, provided adequate data are
      available. A simulated example illustrates use of the methods. LIMITATIONS: If
      the data have small sample size, weak MIC/success relationship, or high
      correlation between MIC-A, MIC-B, this procedure will have poor power.
      CONCLUSION: Discordant MIC analysis may offer a novel path to licensure for
      certain anti-infective drugs.

PMID- 24287134
TI  - An alternative property for evaluating sample size for normal data using
      preliminary data.

PMID- 24287135
TI  - Response.

PMID- 24287136
TI  - Molecular evolution of N-methylputrescine oxidase in tobacco.
AB  - Biosynthesis of nicotine in tobacco requires N-methylputrescine oxidase (MPO),
      which belongs to the copper-containing amine oxidase superfamily. Previous
      studies identified tobacco MPO1 and its close homolog NtDAO1 (formerly called
      MPO2), of which MPO1 has been shown preferentially to oxidize N-methylated
      amines. We show here that NtDAO1, as well as a homologous Arabidopsis diamine
      oxidase (DAO), accept non-N-methylated amines more efficiently than their
      corresponding N-methylated amines. MPO1 is coordinately regulated with other
      nicotine biosynthesis genes with regard to COI1-MYC2-dependent jasmonate
      induction and its dependence on nicotine-specific ERF transcription factors,
      whereas NtDAO1 is constitutively expressed at low basal levels in tobacco plants.
      Both MPO1 and NtDAO1 are targeted to peroxisomes by their C-terminal motifs, and
      the peroxisomal localization of MPO1 is required for it to function in nicotine
      biosynthesis in jasmonate-elicited cultured tobacco cells. Restricted occurrence
      of the MPO subfamily in Nicotiana and Solanum indicates that, during the
      formation of the Solanaceae, MPO has evolved from a DAO, which functions in
      polyamine catabolism within peroxisomes, by optimizing substrate preference and
      gene expression patterns to be suitable for alkaloid formation. 

PMID- 24287137
TI  - Involvement of Arabidopsis histone acetyltransferase HAC family genes in the
      ethylene signaling pathway.
AB  - Epigenetic modifications play a fundamental role in regulating chromatin dynamics
      and gene expression. The level of histone acetylation is controlled by two
      functionally antagonistic enzymes, namely histone acetyltransferase (HAT) and
      histone deacetylase (HDAC). CREB-binding protein (CBP)/p300 proteins, a subfamily
      of highly conserved HATs, are involved in various physiological events including
      proliferation, differentiation and apoptosis. In this work, we study the poorly
      known function of their homologous genes, the HAC genes, in Arabidopsis. We found
      that hac1-involved mutants displayed pleiotropic phenotypes, in particular
      hypersensitivity to ethylene both in the dark and in the light. We also found
      that the transcriptional levels of ethylene-responsive genes are significantly
      higher in the hac1hac5 double mutant than in wild-type plants. Moreover, an
      ethylene synthesis inhibitor cannot release the triple responses of hac mutants.
      These results suggest that HACs are involved in the ethylene signaling pathway. 

PMID- 24287138
TI  - Improved tolerance of metals in contaminated oyster larvae.
AB  - Environmental stress experienced by parents may make a significant difference in
      the response of their offspring. However, relevant studies on marine bivalves are
      very limited especially for the field populations. In the present study, we
      examined the relative metal tolerance of offspring produced by four natural
      populations of oyster Crassostrea sikamea that were contaminated by metals to
      different degrees. We demonstrated that the resistance of oyster offspring to
      copper and zinc was correlated with the level of metal pollution experienced by
      the parent oysters. Specifically, the oyster embryo and larvae produced by adult
      oysters from contaminated sites had a much higher tolerance to metal stress than
      those from the reference sites. Furthermore, tissue concentration-dependent
      maternal transfer of Cu and Zn was found in this study, and the metallothionein
      concentrations in eggs were positively related to the total concentrations of
      maternally transferred Cu and Zn. Thus, the maternally transferred metals
      inducing high level of MT synthesis in eggs was one of the possible mechanisms
      responsible for the enhanced metal tolerance of oyster embryos and larvae from
      heavily contaminated sites. We concluded that environmental exposure history of
      adult oysters significantly influenced the ability of their offspring to cope
      with metal stress. Our findings offered the field evidence of the possible
      transfer of metal tolerance from adults to offspring in marine bivalves. 

PMID- 24287139
TI  - Risk assessment of nitrate and oxytetracycline addition on coastal ecosystem
      functions.
AB  - Diatoms dominate phytoplankton communities in the well-mixed coastal and
      upwelling regions. Coastal diatoms are often exposed to both aquaculture
      pollution and eutrophication. But how these exposures influence on coastal
      ecosystem functions are unknown. To examine these influences, a coastal centric
      diatom, Conticribra weissflogii was maintained at different concentrations of
      nitrate (N) and/or oxytetracycline (OTC). Algal density, cell growth cycle,
      protein, chlorophyll a, superoxide dismutase (SOD) activity, and malonaldehyde
      (MDA) were determined for the assessment of algal biomass, lifetime, nutritional
      value, photosynthesis and respiration, antioxidant capacity, and lipid
      peroxidation, respectively. When N addition was combined with OTC pollution, the
      cell growth cycles were shortened by 56-73%; algal density, SOD activities, the
      concentrations of chlorophyll a, protein, and MDA varied between 73 and 121%, 19
      and 397%, 52 and 693%, 19 and 875%, and 66 and 2733% of the values observed in N
      addition experiments, respectively. According to P-value analysis, the influence
      of OTC on algal density and SOD activity was not significant, but the effect on
      cell growth cycle, protein, chlorophyll a, and MDA were significant (P<0.05). The
      influence of N addition with simultaneous OTC pollution on the above six end
      points was significant. Algal biomass, lifetime, nutrition, antioxidant capacity,
      lipid peroxidation, photosynthesis, and respiration were all affected by the
      addition of OTC and N. Coastal ecosystem functions were severely affected by N
      and OTC additions, and the influence was increased in the order: N<OTC<OTC+N.
      Thus, the simultaneous monitoring of N and OTC was necessary for the risk
      assessment of aquaculture pollution on coastal ecosystem functions. 

PMID- 24287141
TI  - Mitigation of radiation-induced hematopoietic injury via regulation of cellular
      MAPK/phosphatase levels and increasing hematopoietic stem cells.
AB  - Here we describe a novel strategy for mitigation of ionizing radiation-induced
      hematopoietic syndrome by suppressing the activity of MKP3, resulting in ERK
      activation and enhanced abundance of hematopoietic stem cells, using the
      antioxidant flavonoid baicalein (5,6,7-trihydroxyflavone). It offered complete
      protection to mouse splenic lymphocytes against radiation-induced cell death.
      Inhibitors of ERK and Nrf-2 could significantly abrogate baicalein-mediated
      radioprotection in lymphocytes. Baicalein inhibited phosphatase MKP3 and thereby
      enhanced phosphorylation of ERK and its downstream proteins such as Elk and Nrf
      2. It also increased the nuclear levels of Nrf-2 and the mRNA levels of its
      dependent genes. Importantly, baicalein administration to mice before radiation
      exposure led to significant recovery of loss of bone marrow cellularity and also
      inhibited cell death. Administration of baicalein increased the hematopoietic
      stem cell frequency as measured by side-population assay and also by antibody
      staining. Further, baicalein offered significant protection against whole-body
      irradiation (WBI; 7.5Gy)-induced mortality in mice. Interestingly, we found that
      baicalein works by activating the same target molecules ERK and Nrf-2 both in
      vitro and in vivo. Finally, administration of all-trans-retinoic acid (inhibitor
      of Nrf-2) significantly abrogated baicalein-mediated protection against WBI
      induced mortality in mice. Thus, in contrast to the generalized conception of
      antioxidants acting as radioprotectors, we provide a rationale that antioxidants
      exhibit pleiotropic effects through the activation of multiple cellular signaling
      pathways. 

PMID- 24287140
TI  - Demonstration of lumpy skin disease virus infection in Amblyomma hebraeum and
      Rhipicephalus appendiculatus ticks using immunohistochemistry.
AB  - Lumpy skin disease (LSD) is caused by lumpy skin disease virus (LSDV), a member
      of the genus Capripoxvirus. Transmission of the virus has been associated with
      haematophagous insects such as Stomoxys calcitrans as well as Aedes and Culex
      species of mosquitoes. Recent studies have reported the transmission of the virus
      by Amblyomma hebraeum, Rhipicephalus appendiculatus, and Rhipicephalus
      decoloratus ticks and the presence of LSDV in saliva of A. hebraeum and R.
      appendiculatus ticks. The aim of this study was to determine which tick organs
      become infected by LSDV following intrastadial infection and transstadial
      persistence of the virus in A. hebraeum and R. appendiculatus ticks. Nymphal and
      adult ticks were orally infected by feeding them on LSDV-infected cattle.
      Partially fed adult ticks were processed for testing while nymphs were fed to
      repletion and allowed to moult to adults before being processed for testing. The
      infection in tick organs was determined by testing for the presence of the viral
      antigen using monoclonal antibodies with immunohistochemical staining. The viral
      antigen was detected in salivary glands, haemocytes, synganglia, ovaries, testes,
      fat bodies, and midgut. Since the virus was shown to be able to cross the midgut
      wall and infect various tick organs, this may indicate potential for biological
      development and transmission of LSDV in ticks. This study strengthens the
      previously reported evidence of the occurrence of LSDV in tick saliva. 

PMID- 24287143
TI  - Ascidian (chordate-tunicate) and mammalian heparin enemas attenuate experimental
      diversion colitis.
AB  - AIM: We sought to investigate whether mammalian or ascidian Styela plicata
      heparin enemas could diminish inflammation in experimental diversion colitis.
      METHODS: Wistar-specific pathogen-free rats were submitted to a Hartmann's end
      colostomy and treated with enemas containing mammalian or Styela plicata heparin,
      or saline. Enemas were administered 3 times a week in the excluded colon segment
      from 4 to 8 weeks after operation. The effect of treatment was evaluated using
      video-endoscopic and histologic scores, measuring the cytokines interleukin (IL)
      1beta, IL-6, tumor necrosis factor (TNF)-alpha, and transforming growth factor
      beta production in organ cultures by enzyme-linked immunosorbent assay,
      quantifying T cells and macrophages, and investigating nuclear factor-kappa B (NF
      kappaB) and external mitogen-activated protein kinase (pERK) activation. RESULTS:
      Treatment with either mammalian or Styela plicata heparins decreased colonoscopic
      and histologic scores (P < .02) and restored the densities of collagen fibers and
      the number of goblet cells (P < .03) in the diverted colon. Both heparin
      treatments decreased the accumulation of T cells and macrophages (P < .03), and
      the activation of NF-kappaB and pERK (P < .04) in the diverted colon. The high
      levels of cytokines IL-1beta, TNF-alpha, and IL-6 from the diversion colitis
      explants decreased (P < .05) to near normal values with heparin treatments.
      CONCLUSION: The improvement of experimental diversion colitis with heparin
      treatments indicates the anti-inflammatory effect of these compounds, even after
      topical administration. Further studies with the nonhemorrhagic heparin obtained
      from the invertebrate Styela plicata will be necessary to confirm its efficacy
      for the treatment of human diversion colitis and possibly other forms of colitis.

PMID- 24287144
TI  - Prognostic delineation of papillary cholangiocarcinoma based on the invasive
      proportion: a single-institution study with 184 patients.
AB  - BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a presumed
      precursor lesion in biliary carcinogenesis, clinicopathologically overlapping
      with papillary cholangiocarcinomas (PCC); however, because IPNB has no
      standardized definition, this relationship remains equivocal. Herein, we aimed to
      develop a new prognostic model for PCC by focusing on the invasive proportion.
      METHODS: Among 644 patients with resected cholangiocarcinoma (1998-2011), 184
      (28%) had intraductal, exophytic, papillary lesions. These were divided into 4
      subsets based on the invasive component: Noninvasive (PCC-1; n = 14), <=10% (PCC
      2; n = 32), 11-50% (PCC-3; n = 60), and >50% (PCC-4; n = 78). The remaining 460
      were identified as non-PCCs (NPCC). RESULTS: Invasion beyond the duct wall and
      regional lymph node metastases were more frequent in NPCC than PCC (P < .001 for
      both). Five-year survival was better for PCC (55%) than NPCC (35%; P < .001),
      indicating the papillary component to be a significant, independent
      prognosticator. PCC-4 and NPCC had similar clinicopathologic features and
      overlapping survival curves: 33% and 35% at 5 years (P = .835), both less than
      those of PCC-1, PCC-2, and PCC-3 (respectively, 92%, 74%, and 64% at 5 years; P <
      .005 in all combinations). Multivariate analysis in PCC showed >50% invasive
      component, nodal metastasis, and a positive operative margin as independent
      predictors. CONCLUSION: PCC survival decreased with progression of the invasive
      component. PCC with >50% invasive component was clinicopathologically similar to
      NPCC. Although IPNB might be nosologically applied only for PCC cases with <=50%
      invasive component, the present prognostic delineation suggests that all PCC
      subgroups belonged to a singular disease group.

PMID- 24287142
TI  - The role of routine fine-needle aspiration in the diagnosis of infected
      necrotizing pancreatitis.
AB  - BACKGROUND: Diagnosing infected necrotizing pancreatitis (INP) may be
      challenging. The aim of this study was to determine the added value of routine
      fine-needle aspiration (FNA) in addition to clinical and imaging signs of
      infection in patients who underwent intervention for suspected INP. METHODS: We
      conducted a post hoc analysis of 208 consecutive patients from a prospective,
      multicenter database who underwent intervention because of suspected INP. In
      retrospect, 3 groups were constructed based on the patients preoperative
      characteristics: Clinical, imaging, and FNA. Patients in the clinical group had
      clinical signs of infection but no gas on preoperative computed tomography (CT)
      and no FNA performed before intervention. Patients in the imaging group had gas
      bubbles on the preoperative CT but no was FNA performed, whereas patients in the
      FNA group had a positive FNA before intervention. The reference standard for
      infection was the culture taken during the first intervention (either catheter
      drainage or necrosectomy). RESULTS: The initial intervention for INP was
      performed a median of 27 days (interquartile range, 20-39) after admission
      without difference between the 3 groups (P = .15). Infection was confirmed in 80%
      of 92 patients of the clinical group, in 94% of 88 patients of the imaging group,
      and in 86% of 28 patients of the FNA group (P = .07). Mortality was 19% and was
      not different between groups (P = .39). CONCLUSION: INP can generally be
      diagnosed based on clinical or imaging signs of infection. FNA may be useful in
      patients with unclear clinical signs and no imaging signs of INP.

PMID- 24287145
TI  - Impact of reconstruction method on visceral fat change after distal gastrectomy:
      results from a randomized controlled trial comparing Billroth I reconstruction
      and roux-en-Y reconstruction.
AB  - BACKGROUND: Visceral fat is one of the causes of metabolic syndrome. Among the
      various types of bariatric surgery, duodenal-jejunal bypass is one of the most
      common procedures. However, the effect of duodenal bypass on fat changes is not
      completely understood. We examined the effect of duodenal bypass on visceral fat
      changes by comparing Billroth I (BI) and roux-en Y (RY) reconstruction in distal
      gastrectomy. METHODS: This retrospective study used data from 221 patients
      registered for a prospective randomized trial that compared BI to RY in distal
      gastrectomy with lymphadenectomy to treat gastric cancer. With a software
      package, we first quantified the visceral fat area (VFA) on cross-sectional
      computed tomography scans obtained at the level of the umbilicus before and 1
      year after surgery, and then determined the impact of duodenal bypass on visceral
      fat changes. RESULTS: Clinicopathological background data did not differ between
      BI and RY. Rates of BMI reduction for BI and RY also did not differ. The VFA
      reduction rate for RY (47.2 +/- 25.5%) was greater than for BI (36.8 +/- 34.2%, P
      = .0104). Adjuvant chemotherapy (chemotherapy versus no chemotherapy, P = .0136),
      type of reconstruction (BI versus RY, P < .0001), and pathologic stage (p stage I
      versus p stage II-IV, P = .0468) correlated significantly with postoperative
      visceral fat loss. Multivariate logistic regression analysis identified
      reconstruction (BI versus RY, P = .0078) as a significant determinant of visceral
      fat loss. CONCLUSION: Visceral fat loss after distal gastrectomy was greater for
      RY than for BI, and duodenal bypass may be associated with reduction of visceral
      fat.

PMID- 24287146
TI  - Predictive power of prothrombin time and serum total bilirubin for postoperative
      mortality after major hepatectomy with extrahepatic bile duct resection.
AB  - BACKGROUND: In 2011, the International Study Group of Liver Surgery defined
      posthepatectomy liver failure using the prothrombin time-international normalized
      ratio (PT-INR) and total serum bilirubin concentration (T-Bil). Data analyzing
      the clinical impact of PT-INR and T-Bil on postoperative mortality, however,
      remain limited, especially for major hepatectomy with extrahepatic bile duct
      resection (HEBR). METHODS: Prospectively collected data from 545 patients who
      underwent HEBR in a single institution from 2002 to 2011 were analyzed. Receiver
      operating characteristics (ROC) analyses of PT-INR and T-Bil on postoperative
      days (POD) 1, 3, and 5 were used to determine optimal cu-off values for
      predicting postoperative mortality. RESULTS: Most of the treated diseases were
      biliary tract cancers, including perihilar cholangiocarcinoma (n = 418),
      gallbladder carcinoma (n = 52), and intrahepatic cholangiocarcinoma (n = 27). The
      mean values for PT-INR and T-Bil on POD 1, 3, and 5 were significantly greater in
      the patients who died owing to postoperative complications than in the patients
      who survived. On POD 5, the area under the ROC curve for predicting postoperative
      mortality and the optimal cutoff value for PT-INR were 0.876 and 1.68,
      respectively, whereas those of T-Bil were 0.889 and 4.0 mg/dL, respectively. A
      combination of PT-INR and T-Bil showed strong predictive power (ie, >40% of the
      patients with values beyond the cutoff value for both PT-INR and T-Bil on POD 5
      died). CONCLUSION: We recommend monitoring both PT-INR and T-Bil to predict
      accurately which patients are at a high risk after HEBR.

PMID- 24287147
TI  - Insulin dependence and pancreatic enzyme replacement therapy are independent
      prognostic factors for long-term survival after operation for chronic
      pancreatitis.
AB  - BACKGROUND: This retrospective, single-center, observational study on
      postoperative long-term results aims to define yet unknown factors for long-term
      outcome after operation for chronic pancreatitis. PATIENTS AND METHODS: We
      analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to
      2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long
      term survival data were provided by the German citizen registration authorities
      for all patients. A quality-of-life questionnaire was sent to surviving patients
      after a mean follow-up of 5.7 years. RESULTS: Surgical principles were resection
      (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%).
      No significant influences of different surgical principles and operative
      procedures on survival, long-term quality of life and pain control could be
      detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year
      survival 90.8%. Multivariate Cox regression analysis revealed that only
      postoperative insulin dependence at the time of hospital discharge (P = .027;
      Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of
      pancreas enzyme replacement therapy at the time of hospital discharge (P = .039;
      Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors
      for survival with significant hazard ratios for long-term survival. Long-term
      improvement in quality of life was reported by 55 of 76 long-term survivors
      (73%). CONCLUSION: Pancreatic enzyme replacement should be standard treatment
      after surgery for chronic pancreatitis at the time of hospital discharge, even
      when no clinical signs of exocrine pancreatic failure exist. This study
      underlines the potential importance of early operative intervention in chronic
      pancreatitis before irreversible endocrine dysfunction is present.

PMID- 24287149
TI  - Nuclear DNA replication initiation in kinetoplastid parasites: new insights into
      an ancient process.
AB  - Nuclear DNA replication is, arguably, the central cellular process in eukaryotes,
      because it drives propagation of life and intersects with many other genome
      reactions. Perhaps surprisingly, our understanding of nuclear DNA replication in
      kinetoplastids was limited until a clutch of studies emerged recently, revealing
      new insight into both the machinery and genome-wide coordination of the reaction.
      Here, we discuss how these studies suggest that the earliest acting components of
      the kinetoplastid nuclear DNA replication machinery - the factors that demarcate
      sites of the replication initiation, termed origins - are diverged from model
      eukaryotes. In addition, we discuss how origin usage and replication dynamics
      relate to the highly unusual organisation of transcription in the genome of
      Trypanosoma brucei. 

PMID- 24287148
TI  - Improved survival after adding dissection of the superior mesenteric vein lymph
      node (14v) to standard D2 gastrectomy for advanced distal gastric cancer.
AB  - BACKGROUND: Extended lymph node dissection in gastric cancer (D3) was proven to
      have no survival benefit compared with a D2 dissection, but whether adding the
      superior mesenteric nodes (No. 14v) to the dissection provides survival benefit
      for gastric cancer patients remains controversial. METHODS: From April 2001 to
      June 2007, 1,661 patients underwent curative resection for middle or lower third
      gastric cancer. Patients were grouped according to No. 14v lymphadenectomy
      (14vD+/14vD-). Clinicopathologic characteristics and treatment-related factors
      were compared between the groups. Overall survival according to the clinical
      stage (Union for International Cancer Control tumor-node-metastasis staging 6th
      edition) was analyzed using the Cox proportional hazard model. RESULTS: The
      incidence of No. 14v lymph node metastasis was 5.0%. There was no difference in
      morbidity or mortality between the 14vD+ and the 14vD- groups. The proportion of
      locoregional recurrence was greater in 14vD- group (P = .018). In clinical stages
      I and II, 14v lymph node dissection did not affect overall survival; in contrast,
      14v lymph node dissection was an independent prognostic factor in patients with
      clinical stage III/IV gastric cancer (hazard ratio, 0.58; 95% confidence
      interval, 0.38-0.88; P = .01). CONCLUSION: Extended D2 gastrectomy including No.
      14v lymph node dissection seems to be associated with improved overall survival
      of patients with clinical stage III/IV gastric cancer in the middle or lower
      third of the stomach.

PMID- 24287150
TI  - Use of sex-sorted sperm in lactating dairy cows upon estrus detection or
      following timed artificial insemination.
AB  - The present study evaluated the use of sex-sorted sperm upon estrus detection
      (ED) or following timed artificial insemination (TAI) in lactating dairy cows.
      Additionally, the effect of the presence of a corpus luteum (CL) at the beginning
      of the TAI protocol was verified. Cows (539 crossbred Gir * Holstein and 87
      Holstein) were classified according to the presence or absence of CL by
      ultrasonography exam. Cows with a CL were randomly assigned into one of two
      groups (CL-ED/AI or CL-TAI), and cows without a CL (NoCL-TAI) received TAI. Cows
      from the CL-ED/AI group received 500mg of cloprostenol intramuscularly and were
      inseminated 12h after ED in the following five days. Cows from the TAI groups (CL
      or NoCL) received TAI. Cows receiving CL-ED/AI had a lower (P<0.0001) service
      rate (45.1%, 101/224) than TAI groups (CL-TAI=94.2%, 180/191 and NoCL-TAI=97.2%,
      205/211). However, cows receiving AI upon ED (CL-ED/AI=31.7%, 32/101) presented
      higher (P=0.03) pregnancy per AI (P/AI) than cows bred following TAI (CL
      TAI=19.4%, 35/180 and NoCL-TAI=23.9%, 49/205). Despite the lower P/AI, cows
      receiving TAI presented greater (P=0.07) proportion of pregnant cows at the end
      of the reproductive program (CL-TAI=18.3%, 35/191 and NoCL-TAI=23.2%, 49/211)
      than those inseminated upon ED (14.3%, 32/224). There was no effect (P=0.45) of
      the presence of a CL at the beginning of the synchronization protocol on P/AI.
      Thus, the use of TAI programs, regardless of the presence of CL in the beginning
      of the synchronization protocol, increases the service and pregnancy rates but
      reduces the P/AI when compared to the use of sex-sorted sperm upon ED. 

PMID- 24287151
TI  - Altering n-3 to n-6 polyunsaturated fatty acid ratios affects prostaglandin
      production by ovine uterine endometrium.
AB  - Consumption of n-3 polyunsaturated fatty acids (PUFAs) is considered beneficial
      to health but effects on fertility remain uncertain. This study investigated the
      effect of n-3 PUFA supplementation on endometrial prostaglandin (PG) production.
      Ovine uterine endometrial cells were cultured to confluence in DMEM/F12 medium
      containing 10% foetal bovine serum. Stromal and epithelial cell populations were
      confirmed by immunocytochemistry. Cultures were supplemented with 0, 20 or 100
      MUM of alpha-linolenic acid (ALA), stearidonic acid (SDA), eicosapentaenoic acid
      (EPA) with lipopolysaccharide (LPS) at 0 and 0.1 MUg/ml, or different
      combinations of EPA with arachidonic acid (AA) in serum-free medium for 24h. PGs
      were quantified using radioimmunoassay and PG-endoperoxide synthase (PTGS)
      isoforms, PGE and PGF synthase (microsomal PGES1 and PGFS) mRNAs by qPCR. LPS
      increased PGE2 production significantly without changing PGF2alpha production,
      causing increased PGE2:PGF2alpha ratios. ALA and SDA increased PGE2, PGF2alpha
      and PGE2:PGF2alpha ratios (P<0.05-0.01) while EPA alone did not affect PG
      generation. AA significantly stimulated PTGS1 and PTGS2 mRNA expression and PGE2
      and PGF2alpha production (P<0.01). The stimulatory effect of AA was attenuated by
      up to 80% (P<0.05) when AA was combined with EPA. The PGE2:PGF2alpha ratio was
      not affected by AA or EPA alone, but increased when these two PUFAs were combined
      (P<0.05). SDA and EPA decreased PTGS1 mRNA expression (P<0.05) but did not alter
      PTGS2 expression. EPA and AA up-regulated mPGES1 expression (P<0.05) without
      affecting PGFS expression. Since AA is preferentially incorporated in uterine
      endometrium to produce 2-series PGs, alteration of PG production by EPA may
      affect many reproductive processes.

PMID- 24287152
TI  - Photodynamic activity of the boronated chlorin e6 amide in artificial and
      cellular membranes.
AB  - Photodynamic tumor-destroying activity of the boronated chlorin e6 derivative
      BACE (chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1
      yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester), previously described in
      Moisenovich et al. (2010) PLoS ONE 5(9) e12717, was shown here to be enormously
      higher than that of unsubstituted chlorin e6, being supported by the data on much
      higher photocytotoxicity of BACE in M-1 sarcoma cell culture. To validate
      membrane damaging effect as the basis of the enhanced tumoricidal activity, BACE
      was compared with unsubstituted chlorin e6 in the potency to photosensitize dye
      leakage from liposomes, transbilayer lipid flip-flop, inactivation of gramicidin
      A ionic channels in planar lipid membranes and erythrocyte hemolysis. In all the
      models comprising artificial and cellular membranes, the photodynamic effect of
      BACE exceeded that of chlorin e6. BACE substantially differed from chlorin e6 in
      the affinity to liposomes and erythrocytes, as monitored by fluorescence
      spectroscopy, flow cytometry and centrifugation. The results support the key role
      of membrane binding in the photodynamic effect of the boronated chlorin e6 amide.

PMID- 24287153
TI  - Editor's Choice: Contemporary treatment of popliteal artery aneurysm in eight
      countries: A Report from the Vascunet collaboration of registries.
AB  - OBJECTIVES: To study contemporary popliteal artery aneurysm (PA) repair. METHODS:
      Vascunet is a collaboration of population-based registries in 10 countries: eight
      had data on PA repair (Australia, Finland, Hungary, Iceland, New Zealand, Norway,
      Sweden, and Switzerland). RESULTS: From January 2009 until June 2012, 1,471 PA
      repairs were registered. There were 9.59 operations per million person years,
      varying from 3.4 in Hungary to 17.6 in Sweden. Median age was 70 years, ranging
      from 66 years in Switzerland and Iceland to 74 years in Australia and New
      Zealand; 95.6% were men and 44% were active smokers. Elective surgery dominated,
      comprising 72% of all cases, but only 26.2% in Hungary and 39.7% in Finland, (p <
      .0001). The proportion of endovascular PA repair was 22.2%, varying from 34.7% in
      Australia, to zero in Switzerland, Finland, and Iceland (p < .0001). Endovascular
      repair was performed in 12.2% of patients with acute thrombosis and 24.1% of
      elective cases (p < .0001). A vein graft was used in 87.2% of open repairs, a
      synthetic or composite graft in 12.7%. Follow-up was until discharge or 30 days.
      Amputation rate was 2.0% overall: 6.5% after acute thrombosis, 1.0% after
      endovascular, 1.8% after open repair, and 26.3% after hybrid repair (p < .0001).
      Mortality was 0.7% overall: 0.1% after elective repair, 1.6% after acute
      thrombosis, and 11.1% after rupture. CONCLUSIONS: Great variability between
      countries in incidence of operations, indications for surgery, and choice of
      surgical technique was found, possibly a result of surgical tradition rather than
      differences in case mix. Comparative studies with longer follow-up data are
      warranted.

PMID- 24287155
TI  - Reassessing the two-year rodent carcinogenicity bioassay: a review of the
      applicability to human risk and current perspectives.
AB  - The 2-year rodent carcinogenicity test has been the regulatory standard for the
      prediction of human outcomes for exposure to industrial and agro-chemicals, food
      additives, pharmaceuticals and environmental pollutants for over 50 years. The
      extensive experience and data accumulated over that time has spurred a vigorous
      debate and assessment, particularly over the last 10 years, of the usefulness of
      this test in terms of cost and time for the information obtained. With renewed
      interest in the United States and globally, plus new regulations in the European
      Union, to reduce, refine and replace sentinel animals, this review offers the
      recommendation that reliance on information obtained from detailed shorter-term,
      6 months rodent studies, combined with genotoxicity and chemical mode of action
      can realize effective prediction of human carcinogenicity instead of the
      classical two year rodent bioassay. The aim of carcinogenicity studies should not
      be on the length of time, and by obligation, number of animals expended but on
      the combined systemic pathophysiologic influence of a suspected chemical in
      determining disease. This perspective is in coordination with progressive
      regulatory standards and goals globally to utilize effectively resources of
      animal usage, time and cost for the goal of human disease predictability.

PMID- 24287154
TI  - Genome-wide age-related DNA methylation changes in blood and other tissues relate
      to histone modification, expression and cancer.
AB  - Epigenetic marks are extensively altered in cancer but may also change in normal
      tissues with age, which is the primary risk factor for most cancers. We conducted
      an epigenome-wide study to identify age-related methylation sites and examine
      their relationship to cancer and other underlying epigenetic marks. We analyzed
      1006 blood DNA samples of women aged 35-76 years from the Sister Study and found
      that 7694 (28%) of the 27 578 CpGs assayed were associated with age (false
      discovery rate, q < 0.05). Using independent data sets, we confirmed 749 'high
      confidence' age-related CpG (arCpGs) sites in normal blood. Based on The Cancer
      Genome Atlas data, we show that these age-related changes are largely concordant
      in a broad variety of normal tissues and that a significantly higher (71-91%, P <
      10(-74)) than expected proportion of increasingly methylated arCpGs (IM-arCpGs)
      were overmethylated in a wide variety of tumor types. IM-arCpGs sites occurred
      almost exclusively at CpG islands and were disproportionately marked with the
      repressive H3K27me3 histone modification (P < 1 * 10(-) (50)). Genes containing
      these IM-arCpG sites were highly enriched for developmental and signaling
      pathways (P < 10(-) (10)). Our findings suggest that as cells acquire methylation
      at age-related sites, they have a lower threshold for malignant transformation
      that may explain in part the increase in cancer incidence with age. 

PMID- 24287156
TI  - PBTK modelling platforms and parameter estimation tools to enable animal-free
      risk assessment: recommendations from a joint EPAA--EURL ECVAM ADME workshop.
AB  - Information on toxicokinetics is critical for animal-free human risk assessment.
      Human external exposure must be translated into human tissue doses and compared
      with in vitro actual cell exposure associated to effects (in vitro-in vivo
      comparison). Data on absorption, distribution, metabolism and excretion in humans
      (ADME) could be generated using in vitro and QSAR tools. Physiologically-based
      toxicokinetic (PBTK) computer modelling could serve to integrate disparate in
      vitro and in silico findings. However, there are only few freely-available PBTK
      platforms currently available. And although some ADME parameters can be
      reasonably estimated in vitro or in silico, important gaps exist. Examples
      include unknown or limited applicability domains and lack of (high-throughput)
      tools to measure penetration of barriers, partitioning between blood and tissues
      and metabolic clearance. This paper is based on a joint EPAA--EURL ECVAM expert
      meeting. It provides a state-of-the-art overview of the availability of PBTK
      platforms as well as the in vitro and in silico methods to parameterise basic
      (Tier 1) PBTK models. Five high-priority issues are presented that provide the
      prerequisites for wider use of non-animal based PBTK modelling for animal-free
      chemical risk assessment.

PMID- 24287159
TI  - Identification of the pathogenic ciliate Pseudocohnilembus persalinus
      (Oligohymenophorea: Scuticociliatia) by fluorescence in situ hybridization.
AB  - Many scuticociliatid ciliates are regarded as devastating pathogens in
      aquaculture. Among these, Pseudocohnilembus persalinus is a facultative pathogen
      that often results in refractory diseases of mariculture fish. Although
      traditional silver staining methods have been successfully used to identify these
      ciliates, their identification is hampered by their small size and their
      morphological similarity to closely related species. We designed an alternative
      method of identification of P. persalinus using an SSU-rDNA targeted
      oligonucleotide probe labeled with a fluorochrome, and optimized in a
      fluorescence in situ hybridization (FISH) protocol. The assay results in a clear
      identification by strong fluorescence signals from the oligonucleotide probe. The
      method can be used for quick and early detection of P. persalinus infections on
      host fish, as well as other susceptible organisms in aquiculture water. It may
      also be used in studies of the geographical distribution of this scuticociliate.

PMID- 24287161
TI  - Mussel-inspired protein-mediated surface functionalization of electrospun
      nanofibers for pH-responsive drug delivery.
AB  - pH-responsive drug delivery systems could mediate drug releasing rate by changing
      the pH values at specific times as per the pathophysiological need of the
      disease. This paper demonstrates that a mussel-inspired protein polydopamine
      coating can tune the loading and releasing rate of charged molecules from
      electrospun poly(epsilon-caprolactone) (PCL) nanofibers in solutions with
      different pH values. In vitro release profiles show that the positive charged
      molecules release significantly faster in acidic than those in neutral and basic
      environments within the same incubation time. The results of fluorescein
      diacetate staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assays show the viability of cancer cells after treatment with
      doxorubicin-released media at different pH values qualitatively and
      quantitatively, indicating that the media containing doxorubicin that were
      released in solutions at low pH values could kill a significantly higher number
      of cells than those released in solutions at high pH values. Together, the pH
      responsive drug delivery systems based on polydopamine-coated PCL nanofibers
      could have potential application in the oral delivery of anticancer drugs for
      treating gastric cancer and in vaginal delivery of anti-viral drugs or anti
      inflammatory drugs, which could raise their efficacy, deliver them to the
      specific target and minimize their toxic side effects. 

PMID- 24287162
TI  - Furthering the understanding of silicate-substitution in alpha-tricalcium
      phosphate: an X-ray diffraction, X-ray fluorescence and solid-state nuclear
      magnetic resonance study.
AB  - High-purity (SupT) and reagent-grade (ST), stoichiometric and silicate-containing
      alpha-tricalcium phosphate (alpha-TCP: ST0/SupT0 and Si-TCP x=0.10: ST10/SupT10)
      were prepared by solid-state reaction based on the substitution mechanism
      Ca3(PO4)(2-x)(SiO4)x. Samples were determined to be phase pure by X-ray
      diffraction (XRD), and Rietveld analysis performed on the XRD data confirmed
      inclusion of Si in the alpha-TCP structure as determined by increases in unit
      cell parameters; particularly marked increases in the b-axis and beta-angle were
      observed. X-ray fluorescence (XRF) confirmed the presence of expected levels of
      Si in Si-TCP compositions as well as significant levels of impurities (Mg, Al and
      Fe) present in all ST samples; SupT samples showed both expected levels of Si and
      a high degree of purity. Phosphorus ((31)P) magic-angle-spinning solid-state
      nuclear magnetic resonance (MAS NMR) measurements revealed that the high-purity
      reagents used in the synthesis of SupT0 can resolve the 12 expected peaks in the
      (31)P spectrum of alpha-TCP compared to the low-purity ST0 that showed
      significant spectral line broadening; line broadening was also observed with the
      inclusion of Si which is indicative of induced structural disorder. Silicon
      ((29)Si) MAS NMR was also performed on both Si-TCP samples which revealed Q(0)
      species of Si with additional Si Q(1)/Q(2) species that may indicate a potential
      charge-balancing mechanism involving the inclusion of disilicate groups;
      additional Q(4) Si species were also observed, but only for ST10. Heating and
      cooling rates were briefly investigated by (31)P MAS NMR which showed no
      significant line broadening other than that associated with the emergence of beta
      TCP which was only realised with the reagent-grade sample ST0. This study
      provides an insight into the structural effects of Si-substitution in alpha-TCP
      and could provide a basis for understanding how substitution affects the
      physicochemical properties of the material. 

PMID- 24287160
TI  - Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for
      intervertebral disc regeneration.
AB  - Intervertebral disc (IVD) disorders and age-related degeneration are believed to
      contribute to lower back pain. There is significant interest in cell-based
      strategies for regenerating the nucleus pulposus (NP) region of the disc;
      however, few scaffolds have been evaluated for their ability to promote or
      maintain an immature NP cell phenotype. Previous studies have shown that NP cell
      laminin interactions promote cell adhesion and biosynthesis, which suggests a
      laminin-functionalized biomaterial may be useful for promoting or maintaining the
      NP cell phenotype. Here, a photocrosslinkable poly(ethylene glycol)-laminin 111
      (PEG-LM111) hydrogel was developed. The mechanical properties of PEG-LM111
      hydrogel could be tuned within the range of dynamic shear moduli values
      previously reported for human NP. When primary immature porcine NP cells were
      seeded onto PEG-LM111 hydrogels of varying stiffnesses, LM111-presenting
      hydrogels were found to promote cell clustering and increased levels of sGAG
      production as compared to stiffer LM111-presenting and PEG-only gels. When cells
      were encapsulated in 3-D gels, hydrogel formulation was found to influence NP
      cell metabolism and expression of proposed NP phenotypic markers, with higher
      expression of N-cadherin and cytokeratin 8 observed for cells cultured in softer
      (<1kPa) PEG-LM111 hydrogels. Overall, these findings suggest that soft, LM111
      functionalized hydrogels may promote or maintain the expression of specific
      markers characteristic of an immature NP cell phenotype. 

PMID- 24287163
TI  - Molecular pathogenesis of chronic cholestatic liver disease: impact on novel
      therapeutic approaches.

PMID- 24287164
TI  - The impact of azithromycin therapy on the airway microbiota in asthma.

PMID- 24287165
TI  - Primary healthcare factors and hospital admission rates for COPD.

PMID- 24287166
TI  - Modafinil improves daytime sleepiness in patients with mild to moderate
      obstructive sleep apnoea not using standard treatments: a randomised placebo
      controlled crossover trial.
AB  - INTRODUCTION: Patients with mild to moderate obstructive sleep apnoea (OSA)
      commonly suffer excessive daytime sleepiness. Continuous positive airway pressure
      (CPAP) has limited effectiveness in reducing sleepiness in milder OSA. Modafinil
      is a wake-promoting drug licensed to treat residual sleepiness in CPAP-treated
      OSA. We hypothesised that modafinil may effectively treat sleepiness in untreated
      mild to moderate OSA. METHODS: Untreated sleepy men with mild to moderate OSA
      (age 18-70, apnoea-hypopnoea index (AHI) 5-30/h, Epworth Sleepiness Scale (ESS)
      >=10) were randomised to receive 200 mg modafinil or matching placebo daily for 2
      weeks before crossing over to the alternative treatment after a minimum 2-week
      washout. Mixed model analysis of variance was used to compare the changes on
      modafinil to placebo while classifying all randomised patients as random factors.
      RESULTS: 32 patients were randomised (mean (SD) AHI 13 (6.4)/h, age 47 (10.7)
      years, ESS 13.6 (3.3), body mass index 28.2 (3.6) kg/m(2)), 29 of whom (91%)
      completed the trial. The primary outcome (ESS) improved more on modafinil than
      placebo (3.6 points, 95% CI 1.3 to 5.8, p=0.003) and the secondary outcome (40
      min driving simulator performance) also improved more on modafinil than placebo
      (steering deviation 4.7 cm, 95% CI 0.8 to 8.5, p=0.018). Psychomotor Vigilance
      Task reciprocal reaction time improved significantly over placebo (0.15 (1/ms),
      95% CI 0.03 to 0.27, p=0.016). Improvements on the Functional Outcomes of Sleep
      Questionnaire were not significant (5.3 points over placebo, 95% CI -1 to 11.6,
      p=0.093). CONCLUSIONS: Modafinil significantly improved subjective sleepiness in
      patients with untreated mild to moderate OSA. The size of this effect is
      clinically relevant at 3-4 ESS points of improvement compared with only 1-2
      points in CPAP clinical trials. Driving simulator performance and reaction time
      also improved on modafinil. CLINICAL TRIAL REGISTRATION: ACTRN#12608000128392.

PMID- 24287167
TI  - Cigarette smoke impairs cytokine responses and BCG containment in alveolar
      macrophages.
AB  - BACKGROUND: There is a strong epidemiological link between smoking and
      tuberculosis (TB), but the association is confounded by socioeconomic and other
      factors. A direct relationship between cigarette smoke and poor treatment-related
      outcomes in patients with TB is therefore questionable. We investigated whether
      constituents of tobacco smoke impair mycobacterial host immune responses in
      vitro. METHODOLOGY: Preparation of a cigarette smoke extract (CSE) from Marlboro
      Red cigarettes was standardised and reproducibility verified by mass
      spectroscopy. Macrophages were derived from peripheral blood monocytes (MDM) and
      alveolar macrophages from bronchoalveolar lavage fluid from healthy non-smoking
      volunteers. Mycobacterial uptake (flow cytometric detection of fluorescence using
      green fluorescent protein-labelled BCG), cytokine responses (ELISA) and
      mycobacterial containment (colony forming units) was evaluated in both macrophage
      populations with and without co-culture with CSE, nicotine and a nicotine
      receptor blocker. RESULTS: Cigarette smoke failed to impair the uptake of
      mycobacteria by monocyte-derived or alveolar macrophages. CSE (vs no CSE) reduced
      the mean (SD) BCG-driven macrophage (MDM) interferon gamma (IFN-gamma), tumour
      necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) responses by 56.4
      (18.6)%, 67.0 (33.4)% and 77.7 (27.7)%, respectively (p<0.001). Nicotine alone
      impaired IL-10 and TNF-alpha production by 48.8 (37)% and 49 (50)%, respectively
      (p<0.05) through an alpha-7 nicotine receptor-independent mechanism. In 5-day
      cultures, CSE impaired mycobacterial (BCG) containment in both monocyte-derived
      and alveolar macrophages. CONCLUSIONS: Cigarette smoke attenuates effector
      cytokine responses and impairs mycobacterial containment within infected human
      macrophages derived from the peripheral blood and alveolar compartments, thus
      supporting the hypothesis that cigarette smoke subverts mycobacteria-related
      immunity.

PMID- 24287168
TI  - Dopamine depletion attenuates some behavioral abnormalities in a
      hyperdopaminergic mouse model of bipolar disorder.
AB  - BACKGROUND: Patients with BD suffer from multifaceted symptoms, including
      hyperactive and psychomotor agitated behaviors. Previously, we quantified
      hyperactivity, increased exploration, and straighter movements of patients with
      BD mania in the human Behavioral Pattern Monitor (BPM). A similar BPM profile is
      observed in mice that are hyperdopaminergic due to reduced dopamine transporter
      (DAT) functioning. We hypothesized that dopamine depletion through alpha-methyl-p
      tyrosine (AMPT) administration would attenuate this mania-like profile. METHODS:
      Male and female DAT wild-type (WT; n=26) and knockdown (KD; n=28) mice on a
      C57BL/6 background were repeatedly tested in the BPM to assess profile robustness
      and stability. The optimal AMPT dose was identified by treating male C57BL/6 mice
      (n=39) with vehicle or AMPT (10, 30, or 100mg/kg) at 24, 20, and 4h prior to
      testing in the BPM. Then, male and female DAT WT (n=40) and KD (n=37) mice were
      tested in the BPM after vehicle or AMPT (30mg/kg) treatment. RESULTS: Compared to
      WT littermates, KD mice exhibited increased activity, exploration, straighter
      movement, and disorganized behavior. AMPT-treatment reduced hyperactivity and
      increased path organization, but potentiated specific exploration in KD mice
      without affecting WT mice. LIMITATIONS: AMPT is not specific to dopamine and also
      depletes norepinephrine. CONCLUSIONS: KD mice exhibit abnormal exploration in the
      BPM similar to patients with BD mania. AMPT-induced dopamine depletion attenuated
      some, but potentiated other, aspects of this mania-like profile in mice. Future
      studies should extend these findings into other aspects of mania to determine the
      suitability of AMPT as a treatment for BD mania.

PMID- 24287169
TI  - Mental health literacy and the experience of depression in a community sample of
      gay men.
AB  - BACKGROUND: Gay men are at higher risk of suffering from a variety of psychiatric
      disorders, yet the mental health literacy of this population has remained largely
      unknown. METHODS: In 2007 and 2011, surveys were conducted among gay men in
      Geneva, Switzerland, recruited by probability-based time-space sampling. Based on
      a case vignette of a man with major depression, respondents were asked a series
      of questions about labelling, perceived risk, and help-seeking beliefs. Men
      meeting caseness for major depression were asked open questions about perceived
      causes and additional help-seeking/self-help. RESULTS: Among the 762 respondents,
      14.7% met diagnostic criteria for major depression (MDD) in the past 12 months.
      The vignette was labelled depression by 44.1% of the entire sample, and 61.9% of
      the men with MDD. Discrimination (33.2%), acceptance or rejection by others
      (21.4%), and loneliness (24.9%) were the most common reasons given for greater
      susceptibility among gay men, yet men with MDD reported problems with
      love/relationship (32.5%) and work (28.9%) as the most common perceived causes of
      recent depression, and problems with love/relationship (21.9%), accepting one's
      homosexuality (21.1%), and family (20.2%) at initial outset. The highest
      proportions of gay men rated non-medical options such as a close friend (91.6%),
      relaxation exercises or meditation (84.4%), and physical activity (83.5%) as
      being helpful for the depression vignette. LIMITATIONS: No probes used for open
      questions, and findings generalizable only to gay men in the sampling scheme.
      CONCLUSIONS: There are many commonalities in labelling, perceived causes, and
      help-seeking with general populations, but also numerous specificities in mental
      health literacy and experience among gay men.

PMID- 24287170
TI  - Preserving an integrated view of informatics.

PMID- 24287171
TI  - Professional and geographical network effects on healthcare information exchange
      growth: does proximity really matter?
AB  - BACKGROUND AND OBJECTIVE: We postulate that professional proximity due to common
      patients and geographical proximity among practice locations are significant
      factors influencing the adoption of health information exchange (HIE) services by
      healthcare providers. The objective of this study is to investigate the direct
      and indirect network effects of these drivers on HIE diffusion. DESIGN: Multi
      dimensional scaling and clustering are first used to create different clusters of
      physicians based on their professional and geographical proximities. Extending
      the Bass diffusion model to capture direct and indirect network effects among
      groups, the growth of HIE among these clusters is modeled and studied. The
      network effects among the clusters are investigated using adoption data over a 3
      year period for an HIE based in Western New York. MEASUREMENT: HIE adoption
      parameters-external sources of influence as well as direct and indirect network
      coefficients-are estimated by the extended version of the Bass diffusion model.
      RESULTS: Direct network effects caused by common patients among physicians are
      much more influential on HIE adoption as compared with previously investigated
      social contagion and external factors. Professional proximity due to common
      patients does influence adoption decisions; geographical proximity is also
      influential, but its effect is more on rural than urban physicians. CONCLUSIONS:
      Flow of patients among different groups of physicians is a powerful factor in HIE
      adoption. Rather than merely following the market trend, physicians appear to be
      influenced by other physicians with whom they interact with and have common
      patients.

PMID- 24287172
TI  - Easily configured real-time CPOE Pick Off Tool supporting focused clinical
      research and quality improvement.
AB  - Real-time alerting systems typically warn providers about abnormal laboratory
      results or medication interactions. For more complex tasks, institutions create
      site-wide 'data warehouses' to support quality audits and longitudinal research.
      Sophisticated systems like i2b2 or Stanford's STRIDE utilize data warehouses to
      identify cohorts for research and quality monitoring. However, substantial
      resources are required to install and maintain such systems. For more modest
      goals, an organization desiring merely to identify patients with 'isolation'
      orders, or to determine patients' eligibility for clinical trials, may adopt a
      simpler, limited approach based on processing the output of one clinical system,
      and not a data warehouse. We describe a limited, order-entry-based, real-time
      'pick off' tool, utilizing public domain software (PHP, MySQL). Through a web
      interface the tool assists users in constructing complex order-related queries
      and auto-generates corresponding database queries that can be executed at
      recurring intervals. We describe successful application of the tool for research
      and quality monitoring. 

PMID- 24287173
TI  - The compromised inflammatory response to bacterial components after pediatric
      cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like
      receptor signal transduction pathways.
AB  - PURPOSE: Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often
      elicits a systemic inflammatory response followed by a compromised immune
      response, which has been attributed to the morbidity of postoperative infection;
      however, the underlying mechanism(s) has not yet been fully elucidated. We
      hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal
      transduction pathways, thereby causing an immunosuppressive state after pediatric
      cardiac surgery. METHODS: We examined 20 children with congenital heart disease
      undergoing pediatric cardiac surgery. RESULTS: Cardiopulmonary bypass
      differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)
      stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines,
      with significantly diminished tumor necrosis factor alpha, interleukin (IL)
      1beta, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent
      with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP
      activated TLR signal transduction pathways in monocytes with down-regulated
      expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear
      factor kappaB p65, p38, and extracellular signal-regulated kinase 1/2.
      CONCLUSIONS: These results indicate that CPB during pediatric cardiac surgery
      causes substantially reduced production of inflammatory cytokines in response to
      bacterial component LPS or BLP stimulation, which is associated with CPB-induced
      suppression of TLR-mediated signal transduction pathways. This reduced
      inflammatory response after CPB in children with congenital heart disease may
      predispose them to an increased risk of postoperative infection.

PMID- 24287174
TI  - Computerized physician order entry in the cardiac intensive care unit: effects on
      prescription errors and workflow conditions.
AB  - PURPOSES: To evaluate the effects of a computerized physician order entry (CPOE)
      system in the cardiac intensive care unit by detecting prescription errors (PEs)
      and also to assess the impact on working conditions. METHODS: A longitudinal,
      prospective, before-after study was conducted during the periods before and after
      the implementation of the CPOE system. Clinical pharmacists were responsible for
      the registration, description and classification of PEs, and their causes and
      severity, according to an international taxonomy. Professionals were also
      surveyed for their opinion, concerns, and level of satisfaction. RESULTS: A total
      of 470 treatment orders containing 5729 prescriptions were evaluated. The CPOE
      resulted in a marked reduction in the number of PEs: error rate was 44.8% (819
      errors among 1829 prescriptions) with handwritten orders and 0.8% (16 among 2094
      prescriptions) at the final electronic phase (P < .001). Lapses were the main
      cause of error in both prescription methods. Most errors did not reach the
      patients. Errors related with the computerized system were scarce. Most users
      were satisfied with many aspects of this technology, although a higher workload
      was reported. CONCLUSIONS: Computerized physician order entry in the cardiac
      intensive care unit proved to be a safe and effective strategy in reducing PEs
      and was globally well received by professionals.

PMID- 24287175
TI  - The impact of patient cost-sharing on low-income populations: evidence from
      Massachusetts.
AB  - Greater patient cost-sharing could help reduce the fiscal pressures associated
      with insurance expansion by reducing the scope for moral hazard. But it is
      possible that low-income recipients are unable to cut back on utilization wisely
      and that, as a result, higher cost-sharing will lead to worse health and higher
      downstream costs through increased use of inpatient and outpatient care. We use
      exogenous variation in the copayments faced by low-income enrollees in the
      Massachusetts Commonwealth Care program to study these effects. We estimate
      separate price elasticities of demand by type of service. Overall, we find price
      elasticities of about -0.16 for this low-income population - similar to
      elasticities calculated for higher-income populations in other settings. These
      elasticities are somewhat smaller for the chronically sick, especially for those
      with asthma, diabetes, and high cholesterol. These lower elasticities are
      attributable to lower responsiveness to prices across all categories of service,
      and to some statistically insignificant increases in inpatient care. 

PMID- 24287176
TI  - High-normal albuminuria predicts metabolic syndrome in middle-aged Korean men: a
      prospective cohort study.
AB  - OBJECTIVE: High-normal albuminuria has recently been associated with an elevated
      risk of cardiovascular disease. However, it is uncertain whether high-normal
      albuminuria is associated with metabolic syndrome (MetS). The objective of this
      prospective cohort study was to investigate whether a temporal relationship
      exists between a high-normal urine albumin-to-creatinine ratio (UACR) and the
      development of MetS. STUDY DESIGN: A total of 4338 healthy Korean men who had
      their UACRs and MetS components assessed in 2005 were enrolled in the study. A
      MetS-free cohort of 1364 individuals, who did not have any conditions that would
      have excluded them from the study, was followed up until 2010. MAIN OUTCOME
      MEASURE: MetS was defined according to the joint interim statement of the
      International Diabetes Federation Task Force on Epidemiology and Prevention.
      RESULTS: Cox proportional hazards models were used to estimate the hazard ratio
      (HR) associated with normal UACR values stratified into following tertiles: <3.12
      MUg/mg, >=3.12, <4.87 MUg/mg, and >=4.87 MUg/mg. The UACR was categorised into
      the following tertiles. During 4470.6 person-years of follow-up, 247 incident
      cases of MetS developed between 2006 and 2010. The third UACR tertile was
      associated with the development of MetS after adjusting for multiple baseline
      covariates (HR 1.57; 95% confidence interval: 1.14-2.18). CONCLUSIONS: On the
      basis of our 5-year follow-up study, a high-normal UACR predicts the development
      of MetS in Korean men.

PMID- 24287177
TI  - Do-it-yourself healthcare: the current landscape, prospects and consequences.
AB  - The wider availability and increasing use of mHealth tools - covering health
      applications, smartphone plug-ins and gadgets is significant for healthcare. This
      trend epitomises broader trajectories in access to and delivery of healthcare,
      with greater consumer involvement and decentralisation. This shift may be
      conceptualised as 'do-it-yourself Healthcare' - allowing consumers to monitor and
      manage their health, and guide their healthcare consumption. Technology that
      enables data collection by patients informs them about vital health metrics,
      giving them more control over experiences of health or illness. The information
      can be used alone as empowered consumers or together with healthcare
      professionals in an environment of patient-centred care. Current evidence
      suggests a large scope for do-it-yourself Healthcare, given the availability of
      technologies, whilst mHealth tools enhance diagnostics, improve treatment,
      increase access to services and lower costs. There are, however, limitations to
      do-it-yourself Healthcare. Notably, its evidence base is less well developed than
      the availability of technologies to facilitate it. A more complex model and
      understanding is needed to explain motivations for and consequences of engaging
      in do-it-yourself Healthcare. That said, its introduction alongside existing
      medicine may improve quality and reduce costs - potentially improving health
      system sustainability whilst future generations - tomorrow's middle-aged and the
      elderly, will become more conducive to its spread. 

PMID- 24287178
TI  - The utility of absolute risk prediction using FRAX(r) and Garvan Fracture Risk
      Calculator in daily practice.
AB  - OBJECTIVES: There are two commonly used fracture risk prediction tools FRAX((r))
      and Garvan Fracture Risk Calculator (GARVAN-FRC). The objective of this study was
      to investigate the utility of these tools in daily practice. STUDY DESIGN: A
      prospective population-based 5-year follow-up study was conducted in ten general
      practice centres in the Netherlands. For the analyses, the FRAX((r)) and GARVAN
      FRC 10-year absolute risks (FRAX((r)) does not have 5-year risk prediction) for
      all fractures were used. RESULTS: Among 506 postmenopausal women aged >=60 years
      (mean age: 67.8+/-5.8 years), 48 (9.5%) sustained a fracture during follow-up.
      Both tools, using BMD values, distinguish between women who did and did not
      fracture (10.2% vs. 6.8%, respectively for FRAX((r)) and 32.4% vs. 39.1%,
      respectively for GARVAN-FRC, p<0.0001) at group level. However, only 8.9% of
      those who sustained a fracture had an estimated fracture risk >=20% using
      FRAX((r)) compared with 53.3% using GARVAN-FRC. Although both underestimated the
      observed fracture risk, the GARVAN-FRC performed significantly better for women
      who sustained a fracture (higher sensitivity) and FRAX((r)) for women who did not
      sustain a fracture (higher specificity). Similar results were obtained using age
      related cut off points. CONCLUSIONS: The discriminant value of both models is at
      least as good as models used in other medical conditions; hence they can be used
      to communicate the fracture risk to patients. However, given differences in the
      estimated risks between FRAX((r)) and GARVAN-FRC, the significance of the
      absolute risk must be related to country-specific recommended intervention
      thresholds to inform the patient.

PMID- 24287179
TI  - Glycosyl rotation and distortion by key residues in Endocellulase Cel6A from
      Theromobifida fusca.
AB  - Endocellulases are one kind of the important biodegrading cellulose enzymes.
      Experimental results show that a rotated and distorted preactivated structure
      exists before the substrate entering the transition state. The molecular dynamic
      simulation of endocellulase Cel6A models revealed a correlation between the
      rotation and distortion of pyranoside ring in -1 glycosyl unit of the substrate.
      The two key residues, Tyr73 and Ser189, in Cal6A cooperate to rotate and distort
      the pyranoside ring in the cellulose hydrolysis. 

PMID- 24287180
TI  - Aberrant expression of SIRT3 is conversely correlated with the progression and
      prognosis of human gastric cancer.
AB  - SIRT3 is a NAD(+)-dependent histone deacetylaseand and plays a critical role in
      various human carcinomas. However, its precise role in the pathogenesis of
      gastric cancer (GC) is still unclear. Western blot and Real-Time PCR were used to
      detect the protein and mRNA level of SIRT3 in freshly collected samples from GC
      patients. Immunohistochemistry staining was adopted to determine the expression
      of SIRT3 in 65 formalin-fixed, paraffin-embedded samples from GC patients. In
      addition, western blot was used to detect the protein levels of SIRT3 and HIF
      1alpha in gastric cancer cells MGC-803 transfected with SIRT3 or control siRNA.
      Western blot analysis of 25 samples from GC patients showed that 64% (16/25) of
      patients exhibited decreased expression of SIRT3, whereas 4.0% (1/25) of patients
      displayed complete loss. In addition, Real-Time PCR analysis showed that GC
      patients had decreased expression of SIRT3 mRNA. Furthermore,
      immunohistochemistry analysis of 65 formalin-fixed, paraffin-embedded samples
      from GC patients showed that 67.7% (44/65) had decreased SIRT3 staining in the
      cancer tissues. Notably, the expression level of SIRT3 was inversely correlated
      with clinicopathological variable, including tumor infiltration, tumor
      differentiation and tumor stage and 5-year survival of these patients. In vitro
      experiment showed that knockdown of SIRT3 in MGC-803 gastric cancer cells
      significantly increased the expression of HIF-1alpha. Our results provide the
      first evidence showing that an aberrantly decreased expression of SIRT3 occurred
      in GC patients, suggesting that SIRT3 might function as a mitochondrial tumor
      suppressor in GC. Furthermore, the possible mechanism by which SIRT3 affect the
      progress of GC is its direct control of HIF-1alpha. 

PMID- 24287181
TI  - The cataract-associated V41M mutant of human gammaS-crystallin shows specific
      structural changes that directly enhance local surface hydrophobicity.
AB  - The major crystallins expressed in the human lens are gammaS-, gammaC- and gammaD
      crystallins. Several mutations in gammaS-crystallin are associated with
      hereditary cataracts, one of which involves the substitution of a highly
      conserved Valine at position 41 to Methionine. According to a recent report, the
      mutant protein, V41M, shows lower stability and increased surface hydrophobicity
      compared to the wild-type, and a propensity for self-aggregation. Here we address
      the structural differences between the two proteins, with residue-level
      specificity using NMR spectroscopy. Based on the structural model of the mutant
      protein, our results clearly show that the mutation creates a major local
      perturbation almost at the junction of the first and second "Greek-key" motifs in
      the N-terminal domain. A larger section of the second motif (residues 44-86)
      appears to be mainly affected. Based on the sizeable chemical shift of the imino
      proton of the indole side-chain of Trp46 in V41M, we suggest that the sulphur
      atom of Met41 is involved in an S-pi interaction with Trp46. This interaction
      would bring the last beta-strand of the first "Greek-key" motif closer to the
      first beta-strand of the second motif. This appears to lead to a domino effect,
      towards both the N- and C-terminal ends, even as it decays off substantially
      beyond the domain interface. During this process discreet hydrophobic surface
      patches are created, as revealed by ANS-binding. Such changes would not affect
      the secondary structure or cause a major change in the tertiary structure, but
      can lead to self-aggregation or aberrant binding interactions of the mutant
      protein in vivo, and lead to lens opacity or cataract. 

PMID- 24287182
TI  - Age-related disruption of autophagy in dermal fibroblasts modulates extracellular
      matrix components.
AB  - Autophagy is an intracellular degradative system that is believed to be involved
      in the aging process. The contribution of autophagy to age-related changes in the
      human skin is unclear. In this study, we examined the relationship between
      autophagy and skin aging. Transmission electron microscopy and immunofluorescence
      microscopy analyses of skin tissue and cultured dermal fibroblasts derived from
      women of different ages revealed an increase in the number of nascent double
      membrane autophagosomes with age. Western blot analysis showed that the amount of
      LC3-II, a form associated with autophagic vacuolar membranes, was significantly
      increased in aged dermal fibroblasts compared with that in young dermal
      fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of
      autophagic activity. Although lipofuscin autofluorescence was elevated in aged
      dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for
      autophagosome formation-was similar between young and aged dermal fibroblasts,
      suggesting that the increase of autophagosomes in aged dermal fibroblasts was due
      to impaired autophagic flux rather than an increase in autophagosome formation.
      Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which
      mimic the condition of aged dermal fibroblasts with reduced autophagic activity,
      altered the fibroblast content of type I procollagen, hyaluronan and elastin, and
      caused a breakdown of collagen fibrils. Collectively, these findings suggest that
      the autophagy pathway is impaired in aged dermal fibroblasts, which leads to
      deterioration of dermal integrity and skin fragility. 

PMID- 24287183
TI  - Tales of leaving plateaus and scaling new heights!

PMID- 24287184
TI  - Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by
      Coxsackie virus A6.
AB  - A previously well infant aged 9 months presented with an acute, self-limiting
      illness characterised by high fever and a papular eruption that started on the
      face. Although fever subsided within 3 days, the rash worsened and extended over
      the whole body, with some papules evolving into vesiculobullous lesions. The
      infant had been exposed to children with a similar illness 1 week before onset.
      PCR of vesicular swabs and stool samples taken on day 6 of illness showed
      Coxsackie virus A6. The illness resolved within 10 days of onset, although
      onychomadesis was seen on both big toes at follow-up 5 weeks later. Our case
      exemplifies the severe, atypical cases of hand, foot, and mouth disease that have
      been reported worldwide since 2008, and in the USA since the 2011. Atypical hand,
      foot, and mouth disease is caused by a new lineage of Coxsackie virus A6 and is
      characterised by high fever and vesiculobullous eruptions on the calves and backs
      of the hands. Infants with eczema might be predisposed to severe disease. 

PMID- 24287185
TI  - Decrease in antibiotic use, an added benefit of PCVs.

PMID- 24287186
TI  - Effect of pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD
      CV10) on outpatient antimicrobial purchases: a double-blind, cluster randomised
      phase 3-4 trial.
AB  - BACKGROUND: Antimicrobial drugs are frequently prescribed to children for
      respiratory tract infections such as otitis, tonsillitis, sinusitis, and
      pneumonia. We assessed the effect of the ten-valent pneumococcal Haemophilus
      influenzae protein D conjugate vaccine (PHiD-CV10; GlaxoSmithKline) on
      antimicrobial purchases. METHODS: In this nationwide phase 3-4 cluster
      randomised, double-blind trial, children younger than 19 months were randomly
      assigned to receive PHiD-CV10 in 52 of 78 clusters or hepatitis B or A vaccine as
      control in 26 clusters according to three plus one or two plus one schedules
      (infants younger than 7 months) or catch-up schedules (children aged 7-18
      months). The main objective for the antimicrobial treatment outcome was to assess
      vaccine effectiveness against outpatient prescriptions of antimicrobial drugs
      recommended by national treatment guidelines for acute otitis media in Finland in
      children who received at least one dose of study vaccine before 7 months of age.
      Masked follow-up lasted from the date of first vaccination (from Feb 18, 2009,
      through Oct 5, 2010) to Dec 31, 2011. We obtained data on all purchased
      antimicrobial prescriptions through the benefits register of the Social Insurance
      Institution of Finland. This and the nested acute otitis media trial are
      registered at ClinicalTrials.gov, numbers NCT00861380 and NCT00839254. FINDINGS:
      More than 47,000 children were enrolled. In 30,527 infants younger than 7 months
      at enrollment, 98,436 outpatient antimicrobial purchases were reported with
      incidence of 1.69 per person-year in the control clusters. Analysis of the main
      objective included 91% of all antimicrobial purchases: 31,982 in the control and
      57,964 in the PHiD-CV10 clusters. Vaccine effectiveness was 8% (95% CI 1-14) and
      the incidence rate difference 0.12 per person-year corresponding to the number
      needed to vaccinate of five (95% CI 3-67) to prevent one purchase during the 2
      year follow-up for combined PHiD-CV10 three plus one and two plus one infant
      schedules. The vaccine effectiveness was identical for the two infant schedules.
      In the catch-up schedules, the vaccine effectiveness was 3% (95% CI -4 to 10).
      INTERPRETATION: Despite low relative rate reductions the absolute rate reductions
      were substantial because of the high incidence of the outcome. This reduction
      would lead to over 12,000 fewer antimicrobial purchases per year in children
      younger than 24 months in Finland (birth cohort of 60,000 children).

PMID- 24287187
TI  - Semi-rational approach for converting a GH1 beta-glycosidase into a beta
      transglycosidase.
AB  - A large number of retaining glycosidases catalyze both hydrolysis and
      transglycosylation reactions, but little is known about what determines the
      balance between these two activities (transglycosylation/hydrolysis ratio). We
      previously obtained by directed evolution the mutants F401S and N282T of Thermus
      thermophilus beta-glycosidase (Ttbeta-gly, glycoside hydrolase family 1 (GH1)),
      which display a higher transglycosylation/hydrolysis ratio than the wild-type
      enzyme. In order to find the cause of these activity modifications, and thereby
      set up a generic method for easily obtaining transglycosidases from glycosidases,
      we determined their X-ray structure. No major structural changes could be
      observed which could help to rationalize the mutagenesis of glycosidases into
      transglycosidases. However, as these mutations are highly conserved in GH1 beta
      glycosidases and are located around the -1 site, we pursued the isolation of new
      transglycosidases by targeting highly conserved amino acids located around the
      active site. Thus, by single-point mutagenesis on Ttbeta-gly, we created four new
      mutants that exhibit improved synthetic activity, producing disaccharides in
      yields of 68-90% against only 36% when native Ttbeta-gly was used. As all of the
      chosen positions were well conserved among GH1 enzymes, this approach is most
      probably a general route to convert GH1 glycosidases into transglycosidases. 

PMID- 24287188
TI  - Ketamine NMDA receptor-independent toxicity during zebrafish (Danio rerio)
      embryonic development.
AB  - Concerns have been raised that the effect of anaesthetic drugs on the central
      nervous system may result in long-term impairment, namely when ketamine is used
      during embryogenesis. In addition, the cell and molecular basis of anaesthetics
      teratology and toxicity are still uncertain and its implications in the
      development remain to be clarified. More recently, the potential risks for human,
      and animal, exposure through environmental contamination also became an important
      question. In this study, the effects of sub- and over anaesthetic doses of
      ketamine were investigated during zebrafish (Danio rerio) embryonic development
      by exposing zebrafish embryos to ketamine concentrations (0.2, 0.4 and 0.8 mg mL(
      1)) for a period of 20 min during the blastula stage. Ethanol 2% was used as a
      positive control. Morphological parameters, the overall pattern of cell death
      using acridine orange and overall degree of oxidative stress levels by 2,7
      dichlorodihydrofluorescein-diacetate were determined. Lethality and/or
      developmental anomalies were measured based on specific time endpoints until 144
      h post fertilisation. Results showed a concentration-dependent increase in
      anomalies and mortality. Cephalic disorders, enlarged organs and tail/spine
      anomalies were the most prominent deformities observed at 144 hpf. Acridine
      orange images revealed no differences in cellular death pattern in exposed
      embryos at 24 hpf. At the same time point, the cellular redox processes were
      found to be similar among groups. In summary, this study shows that ketamine is
      teratogen and toxic, interfering with the normal developmental pathways of
      embryogenesis, suggesting that ketamine exerts an independent NMDA receptor
      action during the zebrafish blastula stage.

PMID- 24287189
TI  - Sjogren's syndrome: an update on epidemiology and current insights on
      pathophysiology.
AB  - Primary Sjogren's syndrome (pSS) is an autoimmune chronic inflammatory disorder
      affecting 0.2% to 3.0% of the population, with a 9:1 female to male ratio.
      Features are oral and ocular dryness, local and systemic autoantibody production,
      and progressive focal mononuclear cell infiltration in the affected salivary and
      lacrimal glands. Lymphoma is the most severe complication of pSS, occurring in 4%
      to 5% of patients. Genetic studies identified an association with HLA and
      susceptibility genes in cytokine genes and genes involved in B-cell
      differentiation. Genetic variations may help explain why disease manifestations
      differ among patients and supports the hypothesis of certain distinct disease
      phenotypes. 

PMID- 24287190
TI  - Diagnosis of Sjogren's syndrome: American-European and the American College of
      Rheumatology classification criteria.
AB  - Classification criteria provide a formalized approach to studying course and
      management of rheumatic disease, as well as a measure of improvement in care.
      Understanding the purposes of classification criteria sets and the differences
      between different classification criteria is crucial for understanding rheumatic
      disease and for the design and conduct of clinical and epidemiologic
      investigations. In this article, the similarities and differences between the
      American-European Consensus Group Criteria (AECG) and the newly proposed American
      College of Rheumatology (ACR) classification criteria for Sjogren's syndrome and
      the clinical implications of switching to the ACR classification criteria from
      the AECG are described. 

PMID- 24287191
TI  - Salivary gland biopsy for Sjogren's syndrome.
AB  - Salivary gland biopsy is a technique broadly applied for the diagnosis of
      Sjogren's syndrome (SS), lymphoma accompanying SS, sarcoidosis, amyloidosis, and
      other connective tissue disorders. SS has characteristic microscopic findings
      involving lymphocytic infiltration surrounding the excretory ducts in combination
      with destruction of acinar tissue. This article focuses on the main techniques
      used for taking labial and parotid salivary gland biopsies in the diagnostic
      workup of SS with respect to their advantages, their postoperative complications,
      and their usefulness for diagnostic procedures, monitoring disease progression,
      and treatment evaluation. 

PMID- 24287192
TI  - Salivary gland dysfunction and xerostomia in Sjogren's syndrome.
AB  - In this article, salivary gland dysfunction and xerostomia in Sjogren's syndrome
      (SS) are discussed, with a focus on the pathophysiology of salivary dysfunction
      in SS, the clinical presentation of dry mouth in SS, how to assess salivary gland
      hypofunction and xerostomia in SS, and the impact of salivary gland dysfunction
      on quality of life in patients with SS. 

PMID- 24287193
TI  - Oral complications of Sjogren's syndrome.
AB  - Numerous oral manifestations associated with salivary gland dysfunction, and
      particularly Sjogren's syndrome, have been reported in the literature. This
      article discusses the evidence on a wide range of oral manifestations associated
      with Sjogren's syndrome. 

PMID- 24287194
TI  - Management of xerostomia and other complications of Sjogren's syndrome.
AB  - This article provides an overview of the published literature in English in the
      past 63 years involving the management of xerostomia and other oral complications
      of Sjogren's syndrome. The evidence supporting studied interventions was
      evaluated using published criteria.

PMID- 24287195
TI  - Salivary gland disease in Sjogren's syndrome: sialoadenitis to lymphoma.
AB  - Although the cause and molecular pathways of Sjogren's syndrome are still
      unknown, basic, clinical, and translational science have started to identify
      linkages to other known processes. With the advent of newer, more sensitive, and
      more accurate chemokine, cytokine, and genetic analysis, the molecular
      progression of the disease may be understood. The modern technology of
      sialoendoscopy to treat obstructive sialoadenitis from mucous plugging, and the
      addition of rituximab to current chemotherapy, have allowed patients with
      Sjogren's syndrome to have a better quality of life and, if they develop
      lymphomatous changes, a significant increase in their disease remission and
      survival rate. 

PMID- 24287196
TI  - The role of parotidectomy in Sjogren's syndrome.
AB  - Sjogren's syndrome, a chronic and progressive autoimmune disorder mainly
      characterized by xerophthalmia, xerostomia, and parotid enlargement, is primarily
      managed medically, but some patients will require surgical management. Patients
      with Sjogren's syndrome have an increased risk of non-Hodgkin lymphoma.
      Superficial parotidectomy is indicated for diagnostic purposes and can be
      therapeutic in limited circumstances. Surgical indications for parotidectomy in
      Sjogren's syndrome include recurrent parotitis refractory to medical management;
      salivary gland malignancy; and severe, refractory pain. Surgical complications
      include transient or permanent facial nerve injury, post-operative pain,
      persistent inflammation of remnant parotid tissue, Frey syndrome, and facial
      scarring. 

PMID- 24287197
TI  - Extraglandular manifestations of primary Sjogren's syndrome.
AB  - Sjogren syndrome is a chronic autoimmune disease that typically affects the
      salivary and lacrimal glands. Aside from the common glandular signs and symptoms,
      Sjogren syndrome may also cause mononuclear infiltration and immune complex
      deposition involving extraglandular sites producing several extraglandular
      manifestations (EGM). The prevalence of EGMs varies greatly depending on the
      particular manifestation. This article examines the ways that EGMs may present in
      patients with primary Sjogren syndrome. The focus is on the more prevalent and
      significant EGMs including involvement of the nervous system, pulmonary
      manifestations, vasculitis associated with primary Sjogren syndrome, and
      arthropathy. 

PMID- 24287198
TI  - Management of extraglandular manifestations of primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome can have multiple extra-glandular manifestations
      ranging from mild to severe. Treatment for extra-glandular manifestations is
      organ specific and therapies are targeted based on the primary organs involved.
      Preferred treatment options used for extra-glandular manifestations of Sjogren's
      syndrome are usually extrapolated from the physician's experience in treating
      similar manifestations in other autoimmune conditions such as rheumatoid
      arthritis and systemic lupus erythematous. The lack of immunomodulating disease
      modifying drugs in Sjogren's syndrome can be frustrating for patients dealing
      with extra-glandular manifestations, however recent advances in the field has
      made the future look promising for new therapeutic options. 

PMID- 24287199
TI  - Coping strategies and support networks for Sjogren's syndrome patients.
AB  - Sjogren's syndrome is a chronic systemic autoimmune disease that can affect any
      organ system in the body. The most common symptoms are dryness of the mouth and
      eyes resulting from chronic inflammation and a progressive loss of secretory
      function. As with most individuals managing a chronic condition, patients with
      Sjogren's are on a multipronged path to disease and symptom management. Various
      coping strategies are presented in this article and the advantages and
      disadvantages discussed. Additionally, how a support group functions and
      practical guidance for the initiation of a Sjogren's support group are discussed.

PMID- 24287200
TI  - Sjogren's syndrome.

PMID- 24287202
TI  - Wnt/beta-catenin signaling in midbrain dopaminergic neuron specification and
      neurogenesis.
AB  - Loss of midbrain dopaminergic (mDA) neurons underlies the motor symptoms of
      Parkinson's disease. Towards cell replacement, studies have focused on mechanisms
      underlying embryonic mDA production, as a rational basis for deriving mDA neurons
      from stem cells. We will review studies of beta-catenin, an obligate component of
      the Wnt cascade that is critical to mDA specification and neurogenesis. mDA
      neurons have a unique origin--the midbrain floor plate (FP). Unlike the hindbrain
      and spinal cord FP, the midbrain FP is highly neurogenic and Wnt/beta-catenin
      signaling is critical to this difference in neurogenic potential. In beta-catenin
      loss-of-function experiments, the midbrain FP resembles the hindbrain FP, and key
      mDA progenitor genes such as Otx2, Lmx1a, Msx1, and Ngn2 are downregulated
      whereas Shh is maintained. Accordingly, the neurogenic capacity of the midbrain
      FP is diminished, resulting in fewer mDA neurons. Conversely, in beta-catenin
      gain-of-function experiments, the hindbrain FP expresses key mDA progenitor
      genes, and is highly neurogenic. Interestingly, when excessive beta-catenin is
      supplied to the midbrain FP, less mDA neurons are produced suggesting that the
      dosage of Wnt/beta-catenin signaling is critical. These studies of beta-catenin
      have facilitated new protocols to derive mDA neurons from stem cells.

PMID- 24287201
TI  - The structure of Rap1 in complex with RIAM reveals specificity determinants and
      recruitment mechanism.
AB  - The small GTPase Rap1 induces integrin activation via an inside-out signaling
      pathway mediated by the Rap1-interacting adaptor molecule (RIAM). Blocking this
      pathway may suppress tumor metastasis and other diseases that are related to
      hyperactive integrins. However, the molecular basis for the specific recognition
      of RIAM by Rap1 remains largely unknown. Herein we present the crystal structure
      of an active, GTP-bound GTPase domain of Rap1 in complex with the Ras association
      (RA)-pleckstrin homology (PH) structural module of RIAM at 1.65 A. The structure
      reveals that the recognition of RIAM by Rap1 is governed by side-chain
      interactions. Several side chains are critical in determining specificity of this
      recognition, particularly the Lys31 residue in Rap1 that is oppositely charged
      compared with the Glu31/Asp31 residue in other Ras GTPases. Lys31 forms a salt
      bridge with RIAM residue Glu212, making it the key specificity determinant of the
      interaction. We also show that disruption of these interactions results in
      reduction of Rap1:RIAM association, leading to a loss of co-clustering and cell
      adhesion. Our findings elucidate the molecular mechanism by which RIAM mediates
      Rap1-induced integrin activation. The crystal structure also offers new insight
      into the structural basis for the specific recruitment of RA-PH module-containing
      effector proteins by their small GTPase partners. 

PMID- 24287203
TI  - Negative emotionality mediates the association of 5-HTTLPR genotype and
      depression in children with and without ADHD.
AB  - The 44-base-pair polymorphism in the promoter region of the serotonin transporter
      gene (5-HTTLPR) has been implicated in the etiology of depression, but relatively
      little is known about potential mediators of this association. Although
      dimensions of temperament are likely to be proximal to the neurobiological and
      genetic factors underlying depression, studies have yet to formally evaluate
      temperament as a potential causal pathway. We examined individual differences in
      dimensions of temperament [negative emotionality (NE), prosociality (PRO), and
      daring (DA)] as potential mediators of 5-HTTLPR genotype and child depression.
      Using a multiple mediation framework, we tested the association of child 5-HTTLPR
      genotype and these dimensions of temperament with multi-informant ratings of
      child depression in a sample of 218 children with and without attention
      deficit/hyperactivity disorder (ADHD). The long allele of 5-HTTLPR was associated
      with higher NE and lower PRO, but not DA. High NE mediated the association of 5
      HTTLPR genotype and separate parent and teacher ratings of depression. ADHD
      status did not moderate the mediational role of NE for 5-HTTLPR and depression.
      Results suggest that NE may constitute a pathway between 5-HTTLPR and child
      depression. The role of genetic variation and temperament dimensions as
      intermediate traits in the development of depression is discussed. 

PMID- 24287204
TI  - Hepatoprotective properties of sesamin against CCl4 induced oxidative stress
      mediated apoptosis in mice via JNK pathway.
AB  - Sesamin (Ses), one of the major lignan derived from sesame seeds, has been
      reported to have many benefits and medicinal properties. However, its protective
      effects against carbon tetrachloride (CCl4) induced injury in liver have not been
      clarified. The aim of the present study was to investigate the hepatoprotective
      effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our
      data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a
      dose-dependent manner, indicated by both diagnostic indicators of liver damage
      (serum aminotransferase activities) and histopathological analysis. Moreover,
      CCl4-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) in liver, were suppressed by
      treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced
      apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the
      underlying mechanisms of sesamin action, we found that activities of caspase-3
      were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated
      mice. Sesamin increased expression levels of phosphorylated Jun N-terminal
      kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events
      restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2
      proteins and decreasing the release of mitochondrial cytochrome c in liver of
      CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic
      pathways of sesamin effects against CCl4 induced liver injury by regulating the
      expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF
      alpha) and Bak. In conclusion, these results suggested that the inhibition of
      CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant
      activity and its ability to modulate the JNK signaling pathway. 

PMID- 24287205
TI  - Protective effect of iridoid glycosides from Paederia scandens (LOUR.) MERRILL
      (Rubiaceae) on uric acid nephropathy rats induced by yeast and potassium oxonate.
AB  - Iridoid glycosides of Paederia scandens (IGPS) are an active component isolated
      from Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). Uric acid nephropathy
      (UAN) is caused by excessive uric acid, which results in damage of kidney tissue
      via urate crystals deposition in the kidneys. This study aimed to investigate the
      protective effects of IGPS on UAN in rats induced by yeast and potassium oxonate.
      Treatment groups received different doses of IGPS and allopurinol (AP) daily for
      35 days respectively. The results showed that treatment with IGPS significantly
      prevented the increases of uric acid in serum and the elevation of systolic blood
      pressure (SBP), attenuated renal tissue injury, improved renal function and
      reserved the biological activity of NOS-1. IGPS also inhibited the biological
      activity of TNF-alpha and TGF-beta1, and suppressed the mRNA expressions of TNF
      alpha and TGF-beta1 in renal tissue. Taken together, the present and our previous
      findings suggest that IGPS exerts protective effects against kidney damage in UAN
      rats through its uric acid-lowering, anti-inflammatory and immunomodulatory
      properties. Furthermore, decreasing SBP by up regulation of NOS-1 expression and
      down regulation of TNF-alpha and TGF-beta1 expression are involved in the effect
      of IGPS on high uric acid-induced nephropathy.

PMID- 24287206
TI  - Glucose homeostasis and the enteroinsular axis in the horse: a possible role in
      equine metabolic syndrome.
AB  - One of the principal components of equine metabolic syndrome (EMS) is
      hyperinsulinaemia combined with insulin resistance. It has long been known that
      hyperinsulinaemia occurs after the development of insulin resistance. But it is
      also known that hyperinsulinaemia itself can induce insulin resistance and
      obesity and might play a key role in the development of metabolic syndrome. This
      review focuses on the physiology of glucose and insulin metabolism and the
      pathophysiological mechanisms in glucose homeostasis in the horse (compared with
      what is already known in humans) in order to gain insight into the
      pathophysiological principles underlying EMS. The review summarizes new insights
      on the oral uptake of glucose by the gut and the enteroinsular axis, the role of
      diet in incretin hormone and postprandial insulin responses, the handling of
      glucose by the liver, muscle and fat tissue, and the production and secretion of
      insulin by the pancreas under healthy and disrupted glucose homeostatic
      conditions in horses. 

PMID- 24287207
TI  - Body mass index and disability in Chinese nonagenarians and centenarians.
AB  - OBJECTIVES: To examine the potential association between body mass index (BMI)
      and activities of daily living (ADLs) and instrumental activities of daily living
      (IADLs) disabilities in a population-based sample of Chinese nonagenarians and
      centenarians. METHODS: This study analyzed data obtained from a survey conducted
      in 870 elderly Chinese adults aged 90 years or older in Dujiangyan. The
      participants were divided into 4 groups according to the World Health
      Organization (WHO) Asia criteria of underweight, normal weight, overweight, and
      obesity in BMI (<18.5, 18.5-23.0, 23.0-25.0, >=25.0 kg/m(2), respectively) and to
      BMI quartile (<16.8, 16.8-18.9, 18.9-21.1, >=21.1 kg/m(2), respectively). The ADL
      and IADL disabilities were measured using the physical self-maintenance scale
      (PSMS) and IADL scale developed by Lawton and Brody, respectively. RESULTS: The
      participants included in the current statistical analyses were 233 men and 505
      women. The mean age was 93.5 +/- 3.2 years (ranging from 90 to 108 years). Using
      the WHO Asia criteria, the prevalence of underweight and obesity were 43.9% and
      6.6%, respectively. In long-lived women, the prevalence of ADL and IADL
      disabilities was significantly higher in either the underweight group (39.4% and
      72.9%, respectively) or the obesity group (38.1% and 77.7%, respectively)
      compared with the normal weight group (31.4% and 60.8%, respectively). After
      adjusting for relevant covariates, the underweight group and obesity group showed
      significantly increased odds ratios (ORs) for either ADL (1.5 and 1.8,
      respectively) or IADL disability (1.9 and 1.4, respectively). Similar results
      were found when using the BMI quartile. However, in long-lived men, no
      significant difference was found with respect to the prevalence of ADL or IADL
      disability and adjusted ORs among the different BMI groups. CONCLUSIONS: Among
      Chinese long-lived adults, the risk of ADL and IADL disability was higher for
      women with both extremely low and high BMIs, but this pattern was not found in
      men.

PMID- 24287208
TI  - Total dislocation of the talus: a case report.
AB  - Total talar dislocation is a rare injury that is usually open. We report a case
      of closed anterolateral dislocation in a 19 year old, following a fall from a
      bicycle. He was treated with prompt closed reduction. A magnetic resonance
      imaging scan 6 months later showed no signs of avascular necrosis. At 2 years
      follow-up, the patient had a full, pain free, range of motion at the ankle and
      subtalar joints.

PMID- 24287209
TI  - Platelet-rich plasma for the treatment of chronic plantar fasciopathy in adults:
      a case series.
AB  - Plantar fasciopathy (PF) is a common source of pain and disability that is often
      refractory to conservative management. There are no uniformly effective standard
      of-care treatments for chronic recalcitrant PF. Corticosteroid injection is
      considered a viable treatment option when traditional therapies fail, but is
      limited by suboptimal long-term efficacy and potential adverse effects. Platelet
      rich plasma (PRP) is an emerging injection-based treatment for various chronic
      degenerative soft-tissue diseases. It is postulated to promote native tissue
      regeneration; however, consistent scientific evidence remains lacking. A
      prospective case series, including 24 consecutive PF cases, was conducted to
      report patient-rated pain and disability following PRP injection. Foot and Ankle
      Ability Measure (FAAM) scores were the primary clinical outcome measure. Foot
      Single Assessment Numeric Evaluation (Foot-SANE) scores, Short Form-12 Health
      Survey version 2 (SF-12v2) questionnaires, and PRP treatment satisfaction surveys
      were secondary outcome measures. Statistical analysis compared baseline and 32
      weeks post-injection time points. Patients receiving PRP injection reported
      clinically and statistically significant improvement in all outcome measures
      during this interval. There were no serious adverse events associated with
      treatment. PRP is considered a safe therapeutic option with the ability to
      decrease heel pain in patients with chronic PF refractory to appropriate
      conservative management.

PMID- 24287210
TI  - Prevalence of chronic ankle instability in high school and division I athletes.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of chronic
      ankle instability among high school and collegiate athletes. DESIGN: Descriptive
      epidemiological survey. METHODS: Athletes from four high schools and a division I
      university were contacted to participate. For collegiate athletes, a
      questionnaire packet was distributed during preparticipation physicals. For high
      school athletes, parental consent was obtained and then questionnaires were
      distributed during preparticipation physicals, parent meetings, or individual
      team meetings. All athletes completed the Cumberland Ankle Instability Tool for
      both their left and right ankles. Subjects also provided general demographic data
      and completed the Ankle Instability Instrument regarding history of lateral ankle
      sprains and giving way. Athletes were identified as having chronic ankle
      instability if they scored less than 24 on the Cumberland Ankle Instability Tool.
      RESULTS: Of the 512 athletes who completed and returned surveys, 23.4% were
      identified as having chronic ankle instability. High school athletes were more
      likely to have chronic ankle instability than their collegiate counterparts (P <
      .001). Chronic ankle instability was more prevalent among women than among men in
      both high school (P = .01) and collegiate settings (P = .01). CONCLUSIONS:
      Findings of this study revealed differences in the distribution of chronic ankle
      instability that warrant further study.

PMID- 24287211
TI  - Selective lesioning of nucleus incertus with corticotropin releasing factor
      saporin conjugate.
AB  - The nucleus incertus (NI), a brainstem nucleus found in the pontine
      periventricular grey, is the primary source of the neuropeptide relaxin-3 in the
      mammalian brain. The NI neurons have also been previously reported to express
      several receptors and neurotransmitters, including corticotropin releasing
      hormone receptor 1 (CRF1) and gamma-aminobutyric acid (GABA). The NI projects
      widely to putative neural correlates of stress, anxiety, depression, feeding
      behaviour, arousal and cognition leading to speculation that it might be involved
      in several neuropsychiatric conditions. On the premise that relaxin-3 expressing
      neurons in the NI predominantly co-express CRF1 receptors, a novel method for
      selective ablation of the rat brain NI neurons using corticotropin releasing
      factor (CRF)-saporin conjugate is described. In addition to a behavioural deficit
      in the fear conditioning paradigm, reverse transcriptase polymerase chain
      reaction (RT-PCR), western blotting (WB) and immunofluorescence labelling (IF)
      techniques were used to confirm the NI lesion. We observed a selective and
      significant loss of CRF1 expressing cells, together with a consistent decrease in
      relaxin-3 and GAD65 expression. The significant ablation of relaxin-3 positive
      neurons of the NI achieved by this lesioning approach is a promising model to
      explore the neuropsychopharmacological implications of NI/relaxin-3 in
      behavioural neuroscience.

PMID- 24287212
TI  - Hematopoietic stem and progenitor cell activation during chronic dermatitis
      provoked by constitutively active aryl-hydrocarbon receptor driven by Keratin 14
      promoter.
AB  - Polycyclic aromatic hydrocarbons (PAHs) activate aryl-hydrocarbon receptor (AhR).
      Because PAHs are known as a risk factor for allergic diseases, PAH-induced AhR
      activation is expected to be involved in the development of the pathology. We
      previously generated transgenic mice expressing a constitutively active AhR (AhR
      CA) under the control of Keratin 14 (K14) promoter (AhR-CA mouse). The mice
      develop chronic dermatitis with immune imbalance toward Th2 predominance,
      indicating that the AhR activation driven by K14 promoter provokes allergic
      response. Because hematopoietic cells actively participate in the development of
      allergic inflammation, it is important to understand the hematopoietic status
      under allergic conditions. To clarify how the K14 promoter-driven AhR activation
      influences hematopoiesis, we analyzed bone marrow and spleen of AhR-CA mice. We
      verified that AhR-CA was expressed in keratinocytes and thymic epithelial cells
      but not in hematopoietic cells. The AhR-CA mice with full-blown dermatitis
      exhibited leukocytosis and skewed differentiation of hematopoietic progenitor
      cells toward granulocyte-monocyte lineages. They also showed a significant
      expansion of short-term hematopoietic stem cells and multipotent progenitors and
      a subtle reduction in long-term hematopoietic stem cells (LT-HSCs). Their spleens
      were enlarged and abundantly accumulated hematopoietic stem and progenitor cells.
      AhR-CA mice at the early stage of dermatitis did not show leukocytosis or
      splenomegaly but exhibited the granulocyte-monocyte skewing and the reduction in
      LT-HSCs. Thus, AhR activation driven by K14 promoter already alters the
      hematopoietic differentiation and reduces LT-HSCs at the initial stage of
      dermatitis development. These results suggest that nonhematopoietic exposure to
      PAHs triggers allergic response and concomitantly affects hematopoiesis. 

PMID- 24287214
TI  - Open access to Journal of Physiotherapy.

PMID- 24287213
TI  - Bone mineral density at diagnosis determines fracture rate in children with acute
      lymphoblastic leukemia treated according to the DCOG-ALL9 protocol.
AB  - PURPOSE: To elucidate incidence and risk factors of bone mineral density and
      fracture risk in children with Acute Lymphoblastic Leukemia (ALL). METHODS:
      Prospectively, cumulative fracture incidence, calculated from diagnosis until one
      year after cessation of treatment, was assessed in 672 patients. This fracture
      incidence was compared between subgroups of treatment stratification and age
      subgroups (Log-Rank test). Serial measurements of bone mineral density of the
      lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray
      absorptiometry. We evaluated risk factors for a low BMD (multivariate regression
      analysis). Osteoporosis was defined as a BMDLS<=-2 SDS combined with clinical
      significant fractures. RESULTS: The 3-year cumulative fracture incidence was
      17.8%. At diagnosis, mean BMDLS of ALL patients was lower than of healthy peers
      (mean BMDLS=-1.10 SDS, P<0.001), and remained lower during/after treatment
      (8months: BMDLS=-1.10 SDS, P<0.001; 24months: BMDLS=-1.27 SDS, P<0.001; 36months:
      BMDLS=-0.95 SDS, P<0.001). Younger age, lower weight and B-cell-immunophenotype
      were associated with a lower BMDLS at diagnosis. After correction for weight,
      height, gender and immunophenotype, stratification to the high risk (HR)-protocol
      arm and older age lead to a larger decline of BMDLS (HR group: beta=-0.52,
      P<0.01; age: beta=-0.16, P<0.001). Cumulative fracture incidences were not
      different between ALL risk groups and age groups. Patients with fractures had a
      lower BMDLS during treatment than those without fractures. Treatment-related bone
      loss was similar in patients with and without fractures (respectively:
      DeltaBMDLS=-0.36 SDS and DeltaBMDLS=-0.12 SDS; interaction group time, P=0.30).
      Twenty of the 399 patients (5%) met the criteria of osteoporosis. CONCLUSION: Low
      values of BMDLS at diagnosis and during treatment, rather than the treatment
      related decline of BMDLS, determine the increased fracture risk of 17.8% in
      children with ALL.

PMID- 24287215
TI  - Physiotherapist-directed rehabilitation exercises in the outpatient or home
      setting improve strength, gait speed and cadence after elective total hip
      replacement: a systematic review.
AB  - QUESTION: In people who have been discharged from hospital after a total hip
      replacement, do rehabilitation exercises directed by a physiotherapist improve
      strength, gait, function and quality of life? Are these exercises as effective in
      an unsupervised home-based setting as they are in a supervised outpatient
      setting? DESIGN: Systematic review with meta-analysis of randomised trials.
      PARTICIPANTS: Adult patients after elective total hip replacement. INTERVENTION:
      Physiotherapist-directed rehabilitation exercises after discharge from hospital
      following total hip replacement. OUTCOME MEASURES: Hip and knee strength, gait
      parameters, functional measures, and quality of life. RESULTS: Five studies
      comprising 234 participants were included in the review. Sufficient data for meta
      analysis were only obtained for hip and knee strength, gait speed and cadence.
      Physiotherapy rehabilitation improved hip abductor strength by a mean of 16Nm
      (95% CI 10 to 22), gait speed by 6 m/min (95% CI 1 to 11) and cadence by 20
      steps/min (95% CI 8 to 32). Favourable but non-significant improvements in
      strength were noted for other muscle groups at the hip and knee. Function and
      quality of life could not be meta-analysed due to insufficient data and
      heterogeneity of measures, but functional measures tended to favour the
      physiotherapy rehabilitation group. Most outcomes were similar between outpatient
      and home-based exercise programs. CONCLUSION: Physiotherapy rehabilitation
      improves hip abductor strength, gait speed and cadence in people who have been
      discharged from hospital after total hip replacement. Physiotherapist-directed
      rehabilitation exercises appear to be similarly effective whether they are
      performed unsupervised at home or supervised by a physiotherapist in an
      outpatient setting.

PMID- 24287216
TI  - Intensity of challenge to the balance system is not reported in the prescription
      of balance exercises in randomised trials: a systematic review.
AB  - QUESTION: How has balance challenge intensity been reported in trials of balance
      exercise interventions? Are there any instruments designed to measure the
      intensity of balance challenge in balance training exercises? DESIGN: Systematic
      review of randomised trials of balance training exercises. PARTICIPANTS: Older
      adults, ie, the majority of subjects were aged over 55 years. INTERVENTION:
      Balance exercise intervention, or multi-dimensional intervention that included a
      balance exercise intervention. OUTCOME MEASURES: The included trials were
      examined for descriptions and instruments used to report the intensity of the
      challenge to the patient's balance system provided by the balance exercise
      prescribed. The other included studies were examined for instruments that measure
      balance challenge intensity. RESULTS: In most of the 148 randomised trials
      identified, measures of reported balance challenge 'intensity' were actually
      measures of some other aspect of the exercise, eg, aerobic intensity or a
      hierarchy of task difficulty without reference to the patient's ability. Three
      potential systems of measuring the balance challenge intensity were identified.
      Two were not described in any detail. One was defined in terms of the limits of
      the patient's postural stability, but this system appears not to have been
      validated. No adequate measures of balance challenge intensity were found among
      the other types of studies identified. CONCLUSION: The review highlights a
      serious gap in the methods used to prescribe, implement, and evaluate the effect
      of balance exercise programs. Comprehensive work in this area is required to
      develop a psychometrically sound measure of balance exercise intensity.

PMID- 24287217
TI  - Functional electrical stimulation cycling has no clear effect on urine output,
      lower limb swelling, and spasticity in people with spinal cord injury: a
      randomised cross-over trial.
AB  - QUESTION: Does functional electrical stimulation (FES) cycling increase urine
      output and decrease lower limb swelling and spasticity in people with recent
      spinal cord injury? DESIGN: Randomised cross-over trial. PARTICIPANTS: Fourteen
      participants with a recent motor complete spinal cord injury were consecutively
      recruited from two spinal cord injury units in Sydney. INTERVENTION: Participants
      were randomised to an experimental phase followed by a control phase or vice
      versa, with a 1-week washout period in between. The experimental phase involved
      FES cycling four times a week for two weeks and the control phase involved
      standard rehabilitation for two weeks. Assessments by a blinded assessor occurred
      at the beginning and end of each phase. Allocation was concealed and an intention
      to-treat analysis was performed. OUTCOME MEASURES: The primary outcome was urine
      output (mL/hr) and the secondary outcomes were lower limb circumference, and
      spasticity using the Ashworth Scale, and the Patient Reported Impact of
      Spasticity Measure (PRISM). In addition, participants were asked open-ended
      questions to explore their perceptions about treatment effectiveness. RESULTS:
      All participants completed the study. The mean between-group difference (95% CI)
      for urine output was 82mL/hr (-35 to 199). The mean between-group differences
      (95% CI) for lower limb swelling, spasticity (Ashworth), and PRISM were -0.1cm (
      1.5 to 1.2), -1.9 points (-4.9 to 1.2) and -5 points (-13 to 2), respectively.
      All point estimates of treatment effects favoured FES cycling. Participants
      reported many benefits from FES cycling. CONCLUSION: There were no clear effects
      of FES cycling on urine output, swelling and spasticity even though all point
      estimates of treatment effects favoured FES cycling and participants perceived
      therapeutic effects. TRIAL REGISTRATION: ACTRN12611000923965.

PMID- 24287218
TI  - Combined arm stretch positioning and neuromuscular electrical stimulation during
      rehabilitation does not improve range of motion, shoulder pain or function in
      patients after stroke: a randomised trial.
AB  - QUESTION: Does static stretch positioning combined with simultaneous
      neuromuscular electrical stimulation (NMES) in the subacute phase after stroke
      have beneficial effects on basic arm body functions and activities? DESIGN:
      Multicentre randomised trial with concealed allocation, assessor blinding, and
      intention-to-treat analysis. PARTICIPANTS: Forty-six people in the subacute phase
      after stroke with severe arm motor deficits (initial Fugl-Meyer Assessment arm
      score <= 18). INTERVENTION: In addition to conventional stroke rehabilitation,
      participants in the experimental group received arm stretch positioning combined
      with motor amplitude NMES for two 45-minute sessions a day, five days a week, for
      eight weeks. Control participants received sham arm positioning (ie, no stretch)
      and sham NMES (ie, transcutaneous electrical nerve stimulation with no motor
      effect) to the forearm only, at a similar frequency and duration. OUTCOME
      MEASURES: The primary outcome measures were passive range of arm motion and the
      presence of pain in the hemiplegic shoulder. Secondary outcome measures were
      severity of shoulder pain, restrictions in performance of activities of daily
      living, hypertonia, spasticity, motor control and shoulder subluxation. Outcomes
      were assessed at baseline, mid-treatment, at the end of the treatment period (8
      weeks) and at follow-up (20 weeks). RESULTS: Multilevel regression analysis
      showed no significant group effects nor significant time * group interactions on
      any of the passive range of arm motions. The relative risk of shoulder pain in
      the experimental group was non-significant at 1.44 (95% CI 0.80 to 2.62).
      CONCLUSION: In people with poor arm motor control in the subacute phase after
      stroke, static stretch positioning combined with simultaneous NMES has no
      statistically significant effects on range of motion, shoulder pain, basic arm
      function, or activities of daily living. TRIAL REGISTRATION: NTR1748.

PMID- 24287219
TI  - Grip strength is strongly associated with height, weight and gender in childhood:
      a cross sectional study of 2241 children and adolescents providing reference
      values.
AB  - QUESTION: What are reference values for grip strength in children and adolescents
      based on a large and heterogeneous study population? What is the association of
      grip strength with age, gender, weight, and height in this population? DESIGN:
      Cross-sectional study. PARTICIPANTS: Participants were recruited from schools in
      the northern provinces of the Netherlands. The study included healthy children
      and adolescents ranging in age from 4 to 15 years. OUTCOME MEASURES: All children
      had their height (cm) and weight (kg) measured and were allowed a total of four
      attempts using the Jamar hand dynamometer: twice with each hand. Grip strength
      scores (kg) were recorded for the dominant and non-dominant hands. RESULTS: The
      study population comprised 2241 children and adolescents. Reference values for
      both genders are provided according to age and dominance. Grip strength shows a
      linear and parallel progression for both genders until the age of 11 or 12, after
      which grip strength development shows an acceleration that is more prominent in
      boys. CONCLUSION: There is a significant difference in grip strength with each
      ascending year of age in favour of the older group, as well as a trend for boys
      to be stronger than girls in all age groups between 4 and 15 years. Weight and
      especially height have a strong association with grip strength in children.

PMID- 24287220
TI  - Previous injuries and some training characteristics predict running-related
      injuries in recreational runners: a prospective cohort study.
AB  - QUESTIONS: What is the incidence of running-related injuries (RRIs) in
      recreational runners? Which personal and training characteristics predict RRIs in
      recreational runners? DESIGN: Prospective cohort study. PARTICIPANTS: A total of
      200 recreational runners answered a fortnightly online survey containing
      questions about their running routine, races, and presence of RRI. These runners
      were followed-up for a period of 12 weeks. OUTCOME MEASURES: The primary outcome
      of this study was running-related injury. The incidence of injuries was
      calculated taking into account the exposure to running and was expressed by
      RRI/1000 hours. The association between potential predictive factors and RRIs was
      estimated using generalised estimating equation models. RESULTS: A total of 84
      RRIs were registered in 60 (31%) of the 191 recreational runners who completed
      all follow-up surveys. Of the injured runners 30% (n=18/60) developed two or more
      RRIs, with 5/18 (28%) being recurrences. The incidence of RRI was 10 RRI/1000
      hours of running exposure. The main type of RRI observed was muscle injuries
      (30%, n=25/84). The knee was the most commonly affected anatomical region (19%,
      n=16/84). The variables associated with RRI were: previous RRI (OR 1.88, 95% CI
      1.01 to 3.51), duration of training although the effect was very small (OR 1.01,
      95% CI 1.00 to 1.02), speed training (OR 1.46, 95% CI 1.02 to 2.10), and interval
      training (OR 0.61, 95% CI 0.43 to 0.88). CONCLUSIONS: Physiotherapists should be
      aware and advise runners that past RRI and speed training are associated with
      increased risk of further RRI, while interval training is associated with lower
      risk, although these associations may not be causative.

PMID- 24287223
TI  - Wearing pedometers in conjunction with daily step goals and incentives can
      increase physical activity among children.

PMID- 24287222
TI  - Effect of patellar strap and sports tape on jumper's knee symptoms: protocol of a
      randomised controlled trial.
AB  - INTRODUCTION: Patellar straps or sports tapes are commonly used by athletes with
      patellar tendinopathy in order to reduce pain and to continue sports
      participation. Currently, there is no scientific evidence for the effectiveness
      of a patellar strap or sports tape in the management of this common injury. AIM:
      To investigate the effect of the use of a patellar strap and sports tape on pain
      and sports participation in subjects with patellar tendinopathy. DESIGN: The
      study is divided into two parts: a randomised controlled crossover experiment and
      a randomised controlled trial (parallel group design). PARTICIPANTS AND SETTING:
      140 patients diagnosed with patellar tendinopathy recruited from sports medical
      centres and physiotherapist practices. INTERVENTION: In the first part of the
      study, participants serve as their own control by performing three functional
      tests under four different conditions (patellar strap, sports tape, placebo tape,
      and no orthosis). In the second part, participants keep a log for two weeks
      (control week and intervention week) about the pain experienced during and after
      sports and their level of sports participation. In the intervention week
      participants will use the orthosis assigned to them during training and
      competition. MEASUREMENTS: The amount of pain (both parts of the study) and
      sports participation (second part only) will be measured. ANALYSIS: To analyse
      the effects of the orthoses a Linear Mixed Model will be used. DISCUSSION: The
      knowledge gained in this study can be used by practitioners in their advice for
      athletes with patellar tendinopathy about using patellar strap and sports tape
      during sports.

PMID- 24287224
TI  - Sun-style T'ai Chi improves walking endurance and health-related quality of life
      in people with COPD.

PMID- 24287225
TI  - Body-weight supported treadmill training improves cardiovascular fitness and
      walking endurance early after stroke.

PMID- 24287226
TI  - Positive expiratory pressure prevents more exacerbations than high frequency
      chest wall oscillation via a vest in people with cystic fibrosis.

PMID- 24287227
TI  - The Work Limitations Questionnaire (WLQ-25).

PMID- 24287231
TI  - An effective stretching regimen to prevent nocturnal leg cramps.

PMID- 24287228
TI  - Ice-water (cold stress) immersion testing.

PMID- 24287233
TI  - Isolation, identification and cyfluthrin-degrading potential of a novel
      Lysinibacillus sphaericus strain, FLQ-11-1.
AB  - Strain FLQ-11-1, isolated from sewage sludge, was able to degrade cyfluthrin and
      was identified as Lysinibacillus sphaericus based on its morphology, 16S rRNA
      sequence and fatty acid methyl ester (FAME) analyses. This strain could use
      cyfluthrin as its carbon or nitrogen source. Response surface methodology (RSM)
      analysis showed that the optimum conditions for degradation were at pH 7.0 and 35
      degrees C, using an inoculum amount with an OD600nm value of 1.6. Under these
      conditions, approximately 80.4% of cyfluthrin (50 mgl(-1)) was degraded within
      five days (d) of incubation. Four metabolic compounds were detected during
      cyfluthrin degradation and identified as methyl-3-(2,2-dichlorovinyl)-2,2
      dimethyl-(1-cyclopropane)-carboxylate, 4-fluoro-3-phenoxy-benzoic acid methyl
      ester, methyl-3-phenoxybenzoate, 3-phenoxy-benzaldehyde by gas chromatography
      mass spectrometry (GC-MS) and tandem mass spectrum (MS/MS) analysis and no
      cyfluthrin was detected after seven days of incubation. A possible degradation
      pathway was proposed, and our data showed that cyfluthrin could be efficiently
      degraded by FLQ-11-1, indicating that this strain could potentially be used to
      eliminate the contamination of pyrethroid herbicides. 

PMID- 24287234
TI  - The ketogenic diet for the treatment of pediatric status epilepticus.
AB  - BACKGROUND: Refractory status epilepticus carries a high risk of morbidity and
      mortality for children. Traditional treatment of status epilepticus consists of
      multiple anticonvulsant drugs and, if needed, induction of a medical coma. The
      ketogenic diet has been used for intractable epilepsy for many years. The purpose
      of this article is to report a case series of five patients with refractory
      status epilepticus successfully managed with the ketogenic diet. METHODS: A
      summary of pediatric patients with refractory status epilepticus treated with
      diet was performed. CONCLUSIONS: Ketogenic diet therapy should be considered as a
      treatment option in pediatric patients with refractory status epilepticus.

PMID- 24287235
TI  - Epidemiology of limb loss.
AB  - In 2005, 1.6 million people were estimated to be living with limb loss; by 2050,
      the rate is expected to double to 3.6 million in the United States. Past data
      have shown that the rates of dysvascular amputations were increasing. However,
      recent studies looking at single diseases of peripheral arterial disease and
      diabetes mellitus show amputations related to these conditions are now
      decreasing. The authors think that it may not be a single disease process but
      rather the cumulative illness burden that is leading to amputations. In addition
      to cause, age, gender, and race continue to play a role in limb loss.

PMID- 24287236
TI  - Impact of limb loss in the United States.
AB  - The amputee gets lost in the American health care system because of fragmentation
      across the continuum. The journey of the diabetic patient with limb loss through
      the health care system is even more precarious than that of the traumatic
      amputee. Interventions to address these secondary conditions and improve the
      health and outcomes of persons with disability have focused on standard medical
      treatments, such as medication or physical rehabilitation therapies, often to the
      exclusion of psychosocial interventions. Each member of the amputee
      rehabilitation team plays a specific and important role in the care and recovery
      of the person with limb loss.

PMID- 24287237
TI  - Principles of contemporary amputation rehabilitation in the United States, 2013.
AB  - Providing rehabilitation services for the person with an amputation has become
      more difficult in today's health care environment. Amputation rehabilitation
      calls for specialized, multidisciplinary rehabilitation training. In examining
      the principles of amputation rehabilitation, one must understand the lessons
      learned from the Veterans Affairs Amputation System of Care and return to the
      founding principles of rehabilitation medicine. Persons with amputations must be
      reevaluated in a tight program of follow-up care.

PMID- 24287238
TI  - Amputation surgery.
AB  - The best level of amputation must take into consideration the newest socket
      designs, methods of prosthetic suspension, and technologically advanced
      components. In some instances stump revision should be considered, to provide a
      better prosthetic fitting and function. Targeted reinnervation is a new neural
      machine interface that has been developed to help improve the function of
      electrically powered upper prosthetic limbs. Osseointegrated implants for
      prosthetic suspension offer amputees an alternative to the traditional socket
      suspension, and are especially useful for transfemoral and transhumeral levels of
      amputation. Cadaver bone can be used to lengthen an extremely short residual bony
      lever arm.

PMID- 24287239
TI  - Pain issues and treatment of the person with an amputation.
AB  - Most people with amputations should not experience pain that interferes with
      their quality of life or requires regular medication more than 6 months following
      the amputation surgery. In fact, most people with amputations do not experience
      significant pain more than 3 months following the amputation. However, the
      clinician must specifically define what these patients mean when they relate that
      they have pain. The pain must be carefully differentiated to treat it properly.
      Most problematic pain that is present more than 6 months after amputation is
      related to a poorly fitting prosthesis and should be labeled as residual limb
      pain.

PMID- 24287240
TI  - Emotional adaptation to limb loss.
AB  - Individuals experience multiple changes as a result of amputation. These changes
      not only are physical in nature but also may include psychological, financial,
      and comfort changes across the spectrum of an individual's life. It is important
      to assess the emotional responses that an individual may experience postsurgery
      and throughout the rehabilitation process. Grieving is a natural and normal
      emotional response postamputation. Grief resolution is one of the primary areas
      of focus in counseling amputees. This article examines various factors and
      strategies used in the adaptation and recovery from amputation.

PMID- 24287241
TI  - Amputee rehabilitation and preprosthetic care.
AB  - This article reviews occupational therapy treatment and physical therapy
      treatment during preprosthetic training for upper and lower extremity amputees.
      Review of preoperative intervention, preparing the residual limb for the
      prosthesis, instruction in techniques, and adaptive equipment for activities of
      daily living, as well as suggestions for return to vocational and avocational
      activities are addressed.

PMID- 24287242
TI  - Prosthetic choices for people with leg and arm amputations.
AB  - New technology and materials have advanced prosthetic designs to enable people
      who rely on artificial limbs to achieve feats never dreamed before. However, the
      latest and the greatest technology is not appropriate for everyone. The aim of
      this article is to present contemporary options that are available for people who
      rely on artificial limbs to enhance their quality of life for mobility and
      independence.

PMID- 24287243
TI  - Devising the prosthetic prescription and typical examples.
AB  - Limb deficiency has a significant impact on the involved person, with upper limb
      absence presenting a materially different set of issues than lower limb absence.
      The primary objectives in fitting a patient with a prosthesis are to enhance
      their independence in performing daily activities, and to improve their quality
      of life. For lower limb absence, the primary issues are safety, stability, and
      the ability to ambulate in a manner consistent with their overall health. The
      primary objectives in prescribing upper limb prosthetics are function,
      durability, appearance, comfort, and usability of the device. This article
      discusses the nuances associated with managing these patients.

PMID- 24287244
TI  - Prosthetic training: upper limb.
AB  - Ideally, a collaborative team approach is already in place between the certified
      prosthetist (CP) and the occupational therapist (OT) before patients are casted
      for a prosthesis. Once an individual has completed their preprosthetic
      rehabilitation program and received an operational prosthesis from a CP, it is
      imperative that an OT provides prosthetic training. Prosthetic training is
      necessary so that the individual can learn how to use and incorporate the
      prosthesis into their daily life. Prosthetic training consists of 3 main phases:
      controls training, repetitive drills, and bimanual functional skill training.

PMID- 24287245
TI  - Gait analysis in lower-limb amputation and prosthetic rehabilitation.
AB  - Gait analysis combined with sound clinical judgment plays an important role in
      elucidating the factors involved in the pathologic prosthetic gait and the
      selection and effects of available interventions to optimize it. Detailed
      clinical evaluation of walking contributes to the analysis of the prosthetic
      gait, but evaluation in the gait laboratory using kinetic and kinematic data is
      often necessary to quantify and identify the particular contributions of the
      variables impacting the gait with confidence and assess the results of such
      intervention. The same approach can be considered when selecting prosthetic
      components and assessing leg length in this patient population.

PMID- 24287246
TI  - Complications following an amputation.
AB  - In 2005 there were an estimated 1.6 million individuals in the United States
      living with limb loss. This number has been projected to more than double by 2050
      to 3.6 million, making an understanding of management of the individual with
      amputation essential for the physiatrist. This article highlights common
      complications following amputation and discusses the approach to evaluation,
      treatment, and developing management strategies to ensure optimal functional
      outcomes for this population of patients.

PMID- 24287247
TI  - Outcome instruments for prosthetics: clinical applications.
AB  - Outcome measurement is crucial to assuring high-quality patient services and
      improving the quality of services provided by prosthetists. This article
      summarizes recent evidence on the measurement properties of outcome measures, and
      updates previously published summaries of outcome instruments. The review focuses
      on measures of mobility, functional status, quality of life, and patient
      satisfaction, and includes both performance-based and patient-reported outcomes.
      Amputation-specific and general measures that are suitable for patients served by
      prosthetists are discussed. It is encouraging that responsiveness of measures is
      often reported, as this information is needed to improve clinical utility.

PMID- 24287248
TI  - Ideal functional outcomes for amputation levels.
AB  - This article provides a generalized overview of amputation classifications and
      the idealized outcomes for upper and lower amputations at their respective
      levels. The following levels are discussed: above knee/transfemoral, below
      knee/transtibial, above elbow/transhumeral, below elbow/transradial, and
      bilateral for upper and lower extremities. This classification defines a
      framework for clinicians to share with patients so that they understand the
      potential for their expected functional outcomes regarding mobility and
      activities of daily living, both with and without a prosthesis. Moreover, it
      addresses some of the vocational and avocational needs of the individual
      regarding amputation.

PMID- 24287250
TI  - Contemporary amputee rehabilitation.

PMID- 24287252
TI  - Amputee rehabilitation. Preface.

PMID- 24287253
TI  - The surgical results of stapes fixation in children.
AB  - OBJECTIVES: The aims of this study were to review the causes of stapes fixation
      in children undergoing stapes surgery and to analyze the results of stapes
      surgery in children in the short term, at 1 year, and over the long term.
      METHODS: The medical records of 18 children (28 ears) who had undergone stapes
      surgery between January 1999 and December 2012 were retrospectively reviewed. The
      medical history, computed tomography results, intraoperative findings, video
      clips, and hearing outcomes of all patients were reported. RESULTS: The mean age
      of patients was 11.1 years (range, 5.9-15.3 years). Congenital stapes fixation
      (22/28 ears, 79%) and juvenile otosclerosis (6/28 ears, 21%) were responsible for
      all cases of stapes fixation. Intraoperatively, abnormal facial nerves that were
      downwardly displaced over the stapes footplate were noted in four ears.
      Incudostapedotomy was performed in 24 ears, malleostapedotomy in three, and
      partial stapedectomy in one. The early postoperative audiometric outcome was
      favorable in 21 ears (87.5%). There was no significant difference between early
      postoperative (87.5%), 1 year postoperative (91%), and long term (92.3%)
      favorable audiometric results. There was no significant difference in the
      postoperative hearing results between patients with congenital stapes fixation
      and juvenile otosclerosis. CONCLUSION: Congenital stapes fixation was diagnosed
      in 22 (79%) ears and juvenile otosclerosis in six (21%) ears from a series of 28
      ears that were operated on for stapes fixation. Facial nerve anomalies were found
      in four of 22 ears (18%) that had congenital stapes fixation. There was no
      difference in the postoperative hearing results between patients with congenital
      stapes fixation and juvenile otosclerosis. Regardless of the cause of stapes
      fixation, stapedotomy is a safe and effective procedure for managing the
      condition.

PMID- 24287254
TI  - Is day stay adenotonsillectomy safe in children with mild to moderate obstructive
      sleep apnoea? A retrospective review of 100 patients.
AB  - OBJECTIVE: This study explored the perioperative course of 100 children with
      polysomnogram (PSG) proven mild to moderate OSA to evaluate if day stay
      adenotonsillectomy is safe. METHODS: A retrospective chart review of patients who
      had undergone tonsillectomy with or without adenoidectomy following an overnight
      PSG at The Children's Hospital at Westmead Sleep Laboratory. 263 records were
      reviewed. Patients with apnoea hypopnea index (AHI) >= 1 and <15/h and/or a final
      sleep study report of mild to moderate OSA were included. Exclusion criteria were
      age <3 years, weight <10 kg, or any significant co-morbidities or other surgery
      that would preclude day stay surgery. Demographic, PSG and post-operative data
      was analyzed. RESULTS: No major respiratory complications occurred. No patient
      required an unplanned medical review for respiratory concerns, or admission to a
      high care facility. Eleven children left recovery with oxygen prescribed. One
      child had a desaturation to 88% in recovery, and one child had laryngospasm. The
      nine other children required oxygen to maintain saturation >90%. Supplemental
      oxygen was prescribed to 7 patients on the ward. Of these, three patients
      received supplemental oxygen beyond 6h. The other 97 patients had an
      uncomplicated post-operative course and would have been suitable for day-stay
      surgery. Increasing severity of OSA grade on pre-operative PSG was significantly
      associated with post-operative supplemental oxygen use (p=0.003; Cochrane
      Armitage test for trend). CONCLUSIONS: Children who are otherwise well with mild
      to moderate OSA have a sufficiently low risk of respiratory complications
      following adenotonsillectomy to permit day-stay surgery in the setting of
      appropriate facilities with careful post-operative monitoring for the first 6h to
      identify a small sub-group who require overnight observations.

PMID- 24287255
TI  - Localised irradiance distribution found in dental light curing units.
AB  - OBJECTIVE: To measure the localised irradiance and wavelength distributions from
      dental light curing units (LCUs) and establish a method to characterise their
      output. METHODS: Using a laboratory grade integrating sphere spectrometer system
      (Labsphere and Ocean Optics) the power, irradiance, and spectral emission were
      measured at the light tips of four LCUs: one plasma-arc (PAC) unit, one single
      peak blue light-emitting diode (blue-LED) unit, and two polywave LED (poly-LED)
      units. A beam profiler camera (Ophir Spiricon) was used to record the localised
      irradiance across the face of the light tips. The irradiance-calibrated beam
      profile images were then divided into 45 squares, each 1mm(2). Each square
      contained the irradiance information received from approximately 3200 pixels. The
      mean irradiance value within each square was calculated, and the distribution of
      irradiance values among these 45 squares across the tip-ends was examined.
      Additionally, the spectral emission was recorded at various regions across each
      light tip using the integrating sphere with a 4-mm diameter entrance aperture.
      RESULTS: The localised irradiance distribution was inhomogeneous in all four
      lights. The irradiance distribution was most uniformly distributed across the PAC
      tip. Both the irradiance and spectral emission from the poly-LED units were very
      unevenly distributed. CONCLUSIONS: Reporting a single irradiance value or a
      single spectral range to describe the output from a curing light is both
      imprecise and inappropriate. Instead, an image of both the irradiance
      distribution and the distribution of the spectral emission across the light tip
      should be provided. CLINICAL SIGNIFICANCE: The localised beam irradiance profile
      at the tip of dental LCUs is not uniform. Poly-LED units may deliver spectrally
      inhomogeneous irradiance profiles. Depending on the photoinitiator used in the
      RBC and the orientation of the LCU over the tooth, this non-uniformity may cause
      inadequate and inhomogeneous resin polymerisation, leading to poor physical
      properties, and premature failure of the restoration.

PMID- 24287256
TI  - Interface of dentine to root canal sealers.
AB  - OBJECTIVE: Root canal sealers can interact physically or chemically with dentine.
      The aim of this study was to characterize the dentine-root canal sealer interface
      of experimental sealers based on Portland cement using an epoxy-based vehicle in
      comparison to an epoxy resin sealer, AH Plus. METHODS: Root canals were
      biomechanically prepared and filled with any one of the four experimental epoxy
      sealers containing Portland cement with micro- and nano-particles of either
      zirconium oxide or niobium oxide radiopacifers, or AH Plus. The dentine-sealer's
      interfaces were assessed by coronal penetration of fluorescent microspheres, the
      penetration of sealers labelled with Rhodamine B inside the dentine tubules
      (following obturation with gutta-percha and sealers using System B technique)
      assessed by confocal laser scanning microscopy, and the chemical characterization
      of dentine-sealers interface by scanning electron microscopy (SEM) and energy
      dispersive spectroscopy (EDS) line scans. RESULTS: No penetration of fluorescent
      microspheres at the root-dentine to sealer interface was recorded for all test
      materials. Sealers presented greater ability to penetrate within the dentinal
      tubules at the coronal and mid-root thirds. The experimental sealers containing
      radiopacifier nano-particles exhibited a more homogeneous microstructure along
      the whole length of the canal. EDS-line scans results showed a migration of
      silicon and niobium into dentine. Peak overlap between zirconium and the
      phosphorous compromised the identification of the migration of the zirconium
      oxide into dentine. CONCLUSIONS: All five sealers promoted coronal sealing. The
      experimental sealers exhibited promising characteristics and were comparable to
      AH Plus sealer. Elemental migration of the experimental sealers suggests material
      interaction with dentine which was not displayed by AH Plus.

PMID- 24287257
TI  - Enamel white spot lesions can remineralise using bio-active glass and polyacrylic
      acid-modified bio-active glass powders.
AB  - OBJECTIVE: To evaluate the potential of bio-active glass (BAG) powder and BAG
      containing polyacrylic acid (PAA-BAG) to remineralise enamel white spot lesions
      (WSL). METHODS: 32 human enamel samples with artificial WSLs were assigned to 4
      experimental groups (n=8); (a) BAG slurry, (b) PAA-BAG slurry, (c) "standardised"
      remineralisation solution (positive control) and (d) de-ionised water (negative
      control). Mechanical properties of enamel were assessed using surface and cross
      section Knoop microhardness. Micro-Raman spectroscopy in StreamLineTM scan mode
      was used to scan lesion cross-sections. The intensity of the Raman phosphate peak
      at 959 cm(-1) was fitted and measured producing depth profiles analysed using a
      double-step fitting function. A further 20 samples (n=5) were used to obtain 3D
      images of surfaces using non-contact white light profilometry permitting
      measurement of lesion step height in relation to the sound enamel reference
      level, and to scan the lesion surface using scanning electron microscopy (SEM).
      Data were analysed statistically using one-way ANOVA with Tukey's HSD post-hoc
      tests. RESULTS: BAG, PAA-BAG and the remineralisation solution exhibited
      statistically significantly higher surface and cross-section Knoop microhardness
      compared to the negative control. Micro-Raman spectroscopy detected significantly
      higher phosphate content within the treated groups compared to the negative
      control group. Lesions' depth was not significantly reduced. SEM images revealed
      mineral depositions, with different sizes and shapes, within BAG, PAA-BAG and the
      positive control groups. CONCLUSION: BAG and PAA-BAG surface treatments enhance
      enamel WSL remineralisation, assessed by the resultant improved mechanical
      properties, higher phosphate content and morphological changes within the
      artificial lesions.

PMID- 24287258
TI  - The effect of ozone on progression or regression of artificial caries-like enamel
      lesions in vitro.
AB  - OBJECTIVE: This study investigated the effect of ozone on the progression or
      regression of artificial caries-like lesions on enamel following pH cycling
      conditions in vitro. METHODS: A randomized, single blind, four legs design was
      used. 20 full thickness enamel slabs were allocated to each of the four groups
      which were: Fluoride free toothpaste (control); ozone alone; Reductant/Patient
      Kit alone and a combination of both ozone/Reductant/Patient Kit. Artificial
      lesions were created and subjected to the pH cycling regime for a 14 days period.
      Assessments were carried out before and after the pH cycling on the slabs using
      the microhardness testing and Quantitative Light-induced Fluorescence (QLF).
      RESULTS: Statistical significant difference were found in the percentage change
      of enamel microhardness before and after pH cycling between
      ozone/Reductant/Patient Kit group and all the other three groups of the study, as
      well as between Reductant/Patient Kit group and control. There was a statistical
      significant difference in the change of size and severity of the lesion (DeltaQ)
      between all the three regimes tested and the control with a trend favouring
      ozone/Reductant/Patient Kit group. CONCLUSIONS: In our model, it appeared that
      ozone treatment alone is not effective in protecting the enamel against
      demineralisation or promoting remineralisation, unless combined with the
      Reductant/Patient Kit, which contain high levels of fluoride.

PMID- 24287259
TI  - Association of note quality and quality of care: a cross-sectional study.
AB  - BACKGROUND: While physician notes are known to vary in organisation, content and
      quality, the relationship between note quality and clinical quality is uncertain.
      METHODS: We performed a cross-sectional study of outpatient visit physician notes
      by adult patients with coronary artery disease or diabetes mellitus seen in 2010.
      We assessed physician note quality using the 9-item Physician Documentation
      Quality Instrument (PDQI-9) and compared this to disease-specific clinical
      quality scores constructed from data extracted from the electronic health record
      (EHR). We also assessed the presence of typical note subsections, and indicators
      of quality care in physician notes. RESULTS: We evaluated 239 notes, written by
      111 physicians; 110 notes were written by primary care physicians, 52 by
      cardiologists and 77 by endocrinologists. Reason for visit was absent in 10% of
      notes, medication list was not present in the note in 19.7% and timing for follow
      up was absent in 18.0% of notes. Significant copy/pasted material was present in
      10.5% of notes. Laboratory quality indicators were more often found in other EHR
      sections than in the physician note. Clinical quality scores for diabetes and
      coronary artery disease (CAD) showed no significant association with subjective
      note quality (diabetes: r -0.119, p=0.065, CAD: r -0.124, p=0.06). CONCLUSIONS:
      Notes varied in documentation method and length, and important note subsections
      were frequently missing. Key clinical data to support quality patient care were
      often not present in physician notes, but were often found elsewhere in the EHR.
      Subjective assessment of note quality did not correlate with clinical quality
      scores, suggesting that writing high-quality notes and meeting quality measures
      are not mutually reinforcing activities.

PMID- 24287260
TI  - Internal consistency, factor structure and construct validity of the French
      version of the Hospital Survey on Patient Safety Culture.
AB  - OBJECTIVE: To assess the psychometric properties of the French-language version
      of the Hospital Survey on Patient Safety Culture (HSOPSC). METHODS: Data were
      obtained from a staff survey at a Swiss multisite hospital. We computed
      descriptive statistics and internal consistency coefficients, then conducted a
      confirmatory and exploratory factor analysis, and performed construct validity
      tests. RESULTS: 1171 staff members participated (response rate 74%). The internal
      consistency coefficients of the 12 dimension scores ranged from 0.57 to 0.86
      (median 0.73). Confirmatory factor analysis indicated a reasonable but not
      perfect fit of the hypothesised measurement model (root mean square error of
      approximation 0.043, comparative fit index 0.89). Exploratory data analysis
      suggested 10 dimensions instead of 12, grouping items from teamwork across
      hospital units with those of hospital handoffs and transitions, and items from
      communication openness with those of feedback and communication about error.
      However, the loading pattern was clean: 41 of 42 main loadings exceeded 0.40, and
      only 3 of 378 cross-loadings exceeded 0.30. All 10 process scores were higher
      among respondents who rated the global safety grade as 'excellent' or 'very good'
      rather than 'good', 'fair' or 'poor' (effect sizes 0.41-0.79, all p<0.001), but
      score differences between those who have and have not reported an incident in the
      past year were weak or inconsistent with theory. DISCUSSION: The French version
      of the HSOPSC did not perform as well as the original in standard psychometric
      analyses.

PMID- 24287261
TI  - Carboxymethyl cellulose coating decreases toxicity and oxidizing capacity of
      nanoscale zerovalent iron.
AB  - Nanoscale zerovalent iron (NZVI) with modified surface via coating with organic
      stabilizers has been documented with enhanced colloidal stability and dispersity.
      Therefore, the expanded application potential and accompanying intrinsic exposure
      of such nanoparticle can be anticipated. In our study, carboxymethyl cellulose
      (CMC)-stabilized NZVI (CNZVI) exerted minimized oxidative stress response and
      slower disruption of cell membrane integrity, resulting in mitigated cytotoxicity
      towards bacteria Agrobacterium sp. PH-08 as compared with the uncoated
      counterpart. The corrosive oxidation of both nanoparticles in oxygenic water
      provided a better understanding of coating effect. The decreased oxidative
      degradation of probe 4-chlorophenol with CNZVI than NZVI implicated a weaker
      oxidizing capacity, which might overweight massive adhesion-mediated redox damage
      and explain the different exposure outcome. However, enhanced evolution of iron
      oxide as well as the promoted production of hydrogen peroxide adversely
      demonstrated CMC-coating facilitated iron corrosion by oxygen, suggesting CMC was
      most likely to act as a radical scavenger and compete with organics or bacteria
      for oxidants. Moreover, XRD, XPS and TEM results showed that the spherical NZVI
      was oxidized to form needle-shaped iron oxide-hydroxide (gammaFeOOH) with no
      detectable oxidative stress for PH-08, alleviating worries regarding
      exotoxicological impact of iron nanotechnology. 

PMID- 24287262
TI  - Effects of low molecular-weight organic acids and dehydrogenase activity in
      rhizosphere sediments of mangrove plants on phytoremediation of polycyclic
      aromatic hydrocarbons.
AB  - This work evaluated the roles of the low-molecular-weight organic acids (LMWOAs)
      from root exudates and the dehydrogenase activity in the rhizosphere sediments of
      three mangrove plant species on the removal of mixed PAHs. The results showed
      that the concentrations of LMWOAs and dehydrogenase activity changed species
      specifically with the levels of PAH contamination. In all plant species, the
      concentration of citric acid was the highest, followed by succinic acid. For
      these acids, succinic acid was positively related to the removal of all the PAHs
      except Chr. Positive correlations were also found between the removal percentages
      of 4-and 5-ring PAHs and all LMWOAs, except citric acid. LMWOAs enhanced
      dehydrogenase activity, which positively related to PAH removal percentages.
      These findings suggested that LMWOAs and dehydrogenase activity promoted the
      removal of PAHs. Among three mangrove plants, Bruguiera gymnorrhiza, the plant
      with the highest root biomass, dehydrogenase activity and concentrations of
      LMWOAs, was most efficient in removing PAHs. 

PMID- 24287263
TI  - An inhibitory effect of self-assembled soft systems on Fenton driven degradation
      of xanthene dye Rhodamine B.
AB  - Rhodamine B (RhB) is known to be a common organic pollutant despite having
      various technical applications. Treatment of effluents containing such compounds
      is important so as to minimize their effect on environment. Advanced Oxidation
      Processes (Fenton and Fenton like reactions) are such methods that can oxidize
      the contaminants powerfully and non-selectively. This work investigates the
      oxidation kinetics of dye RhB by hydroxyl radical (OH) generated via Fenton
      reaction in presence of surfactant assemblies of varying architectures using
      spectrophotometric, spectrofluorometic and tensiometric methods. The presence of
      surfactants viz. cationics, non-ionics and some binary mixtures in the pre
      micellar and post micellar concentration ranges were found to inhibit the
      degradation of RhB to a varying degree. However, the reaction was totally
      inhibited in anionic surfactant. The experimental data was fitted to a pseudo
      first order kinetic model and the kinetic parameters obtained thereof were
      explained on the basis of the nature and type of interaction between the cationic
      form of RhB and the surfactants of varying architectures. The work has a critical
      significance in view of the fact that degradation studied in presence of
      surfactant assemblies is more representative than studied in aqueous solution
      because such conditions compare well with the conditions prevailing in the
      environment. 

PMID- 24287264
TI  - Integrating classical and molecular approaches to evaluate the impact of
      nanosized zero-valent iron (nZVI) on soil organisms.
AB  - Nanosized zero-valent iron (nZVI) is a new option for the remediation of
      contaminated soil and groundwater, but the effect of nZVI on soil biota is mostly
      unknown. In this work, nanotoxicological studies were performed in vitro and in
      two different standard soils to assess the effect of nZVI on autochthonous soil
      organisms by integrating classical and molecular analysis. Standardised
      ecotoxicity testing methods using Caenorhabditis elegans were applied in vitro
      and in soil experiments and changes in microbial biodiversity and biomarker gene
      expression were used to assess the responses of the microbial community to nZVI.
      The classical tests conducted in soil ruled out a toxic impact of nZVI on the
      soil nematode C. elegans in the test soils. The molecular analysis applied to
      soil microorganisms, however, revealed significant changes in the expression of
      the proposed biomarkers of exposure. These changes were related not only to the
      nZVI treatment but also to the soil characteristics, highlighting the importance
      of considering the soil matrix on a case by case basis. Furthermore, due to the
      temporal shift between transcriptional responses and the development of the
      corresponding phenotype, the molecular approach could anticipate adverse effects
      on environmental biota. 

PMID- 24287265
TI  - Polyaromatic hydrocarbons impair phosphorus transport by the arbuscular
      mycorrhizal fungus Rhizophagus irregularis.
AB  - Phosphate uptake by plant roots is mainly mediated by arbuscular mycorrhizal
      fungi (AMF). However, the impact on phosphorus (P) transport of polycyclic
      aromatic hydrocarbons (PAH), persistent organic pollutants widely found in
      altered soils, is not known up today. Here, we monitored the Rhizophagus
      irregularis fungal growth and the fungal P transport ability from the
      extraradical mycelium to the host transformed chicory roots in the presence of
      anthracene and benzo[a]pyrene (B[a]P) and the combination of both PAH, under in
      vitro conditions. Firstly, our findings showed that PAH have detrimental effect
      on the fungal growth. The combination of both PAH was more toxic than each of the
      PAH individually due to synergistic effects. Secondly, PAH affected the P
      transport by the fungus from the medium to the roots. This was evidenced by
      either the decrease in (33)P quantity transported in the roots as well as the
      decrease in acid phosphatase activity in the mycorrhizal roots. Moreover, the
      fungal alkaline phosphatase activities remained constant in the extraradical
      mycelium as well as in the roots in the absence and in the presence of PAH. The
      GintPT and GiALP (encoding a P transporter and an alkaline phosphatase
      respectively) gene expressions were also found to be similar in the extraradical
      mycelium treated with PAH or not (control). These findings suggested that the P
      uptake by R. irregularis was not affected by PAH but probably the transport from
      the extraradical mycelium to the intraradical mycelium. 

PMID- 24287266
TI  - Immunotoxicity of aluminum.
AB  - Aluminum (Al) is present in the daily life of all humans. With the incidence of
      Al contamination increased in recent years, the toxicity of Al on the immune
      function has attracted more attention. Even with this increased attention, the
      mechanism of Al immunotoxicity still remains unclear. The mechanism of Al
      immunotoxicity reviewed herein focused on the effects of Al on the splenic trace
      elements, the status of alpha-naphthyl acetate esterase (ANAE) cells, cytokines,
      complement and immunoglobulins, as well as macrophages. The studies in the
      literature showed that Al decreased splenic iron (Fe) and zinc (Zn) levels, but
      the effects of Al on splenic copper (Cu) level was ambiguous and controversial.
      Al exposure inhibited levels of ANAE(+) cells, the production of interleukin (IL)
      2 and the functions of macrophages. With respect to other key cytokines, studies
      showed that Al suppressed the production of tumor necrosis factor (TNF)-alpha in
      vitro; effects of Al on TNF-alpha formation in vivo were less overt. Al exposure
      reduced complement 3 (C3) level, but effects of Al exposure on complement 4 (C4)
      level were not as clear-cut. Lastly, the effects of Al exposure on the IgG, IgM
      and IgA levels were conflicting. Taken in totality, the results of several
      studies in the literature demonstrated that Al could impart adverse effects on
      immune function. 

PMID- 24287267
TI  - Developmental origins of the conjoined twin mature embryo sacs in Smilax
      davidiana, with special notes on the formation of their embryos and endosperms.
AB  - PREMISE OF THE STUDY: Smilax davidiana, a perennial deciduous vine in
      Smilacaceae, is widely distributed in East and South China. A recent
      investigation revealed the existence of twin embryo sacs in this species. This
      study describes their mature structure, analyzes their developmental origins, and
      discusses the formation of their embryos and endosperms. METHODS: Conventional
      paraffin section, light microscopy, and various staining techniques were used to
      document the course of megasporogenesis and mature embryo sac structure in
      pistillate flowers. KEY RESULTS: Two chalazal megaspores of the tetrad became
      functional, giving rise to twin embryo sacs. Two mature embryo sacs of the same
      size (equal-conjoined twins); a dominant mature embryo sac and a subordinate one
      (unequal-conjoined twins); or very rarely, fully fused twin mature embryo sacs
      sharing a common chalazal domain are formed. CONCLUSION: A single embryo
      occurring in conjoined twins is the outcome of two eggs competing for sperm
      rather than a result of contention of two pre-embryos (or young embryos) for
      nutrition. Conjoined twin embryo sacs could provide a new pathway to the
      formation of pentaploid endosperms.

PMID- 24287268
TI  - Potomacapnos apeleutheron gen. et sp. nov., a new Early Cretaceous angiosperm
      from the Potomac Group and its implications for the evolution of eudicot leaf
      architecture.
AB  - PREMISE OF THE STUDY: Eudicots diverged early in the evolution of flowering
      plants and now comprise more than 70% of angiosperm species. In spite of the
      importance of eudicots, our understanding of the early evolution of this clade is
      limited by a poor fossil record and uncertainty about the order of early
      phylogenetic branching. The study of Lower Cretaceous fossils can reveal much
      about the evolution, morphology, and ecology of the eudicots. METHODS: Fossils
      described here were collected from Aptian sediments of the Potomac Group exposed
      at the Dutch Gap locality in Virginia, USA. Specimens were prepared by degaging,
      then described and compared with leaves of relevant extant and fossil plants. We
      conducted a phylogenetic analysis of morphological characters using parsimony
      while constraining the tree search with the topology found through molecular
      phylogenetic analyses. KEY RESULTS: The new species is closely related to
      ranunculalean eudicots and has leaf architecture remarkably similar to some
      living Fumarioideae (Papaveraceae). CONCLUSIONS: These are the oldest eudicot
      megafossils from North America, and they show complex leaf architecture
      reflecting developmental pathways unique to extant eudicots. The morphology and
      small size of the fossils suggest that they were herbaceous plants, as is seen in
      other putative early eudicots. The absence of co-occurring tricolpate pollen at
      Dutch Gap either (1) reflects low preservation probability for pollen of
      entomophilous herbs or (2) indicates that some leaf features of extant eudicots
      appeared before the origin of tricolpate pollen.

PMID- 24287269
TI  - Novel treatments of asthma and allergic diseases.
AB  - The prevalence of allergic diseases has considerably increased, mostly in
      industrialized countries (> 20%), and asthma affects approximately 300 million
      individuals worldwide. Current therapies are able to control symptoms although
      they do not modulate immunological dysregulation that characterizes allergic
      diseases. Over the last 30 years, only a few new drugs have been introduced on
      the market and they all act on Th2-type response which has a critical role in the
      pathogenesis of allergic diseases. Recently, a new scenario has been opened on
      Th17-cells, Th1-type cytokines and innate immune system components involved in
      the inflammatory pathogenesis of asthma and other allergic diseases. These
      findings suggest a promising therapeutic role of new agents that block the action
      of specific cytokines. Furthermore, the concept of an intrinsic structural defect
      in the bronchial epithelium paves the way to innovative therapeutic strategies.
      In this review we present an update on therapies for allergic diseases with
      special focus on asthma. 

PMID- 24287270
TI  - Molecular characterization, phylogeny and expression of a hepcidin gene in the
      blotched snakehead Channa maculata.
AB  - A hepcidin-like gene (cmHep) was cloned and characterized from the liver of the
      blotched snakehead Channa maculata. The complete cmHep cDNA was 756 bp in length,
      containing an open reading frame of 270 bp (encoding 89 amino acids), flanked by
      210 bp and 276 bp of 5' and 3' untranslated regions, respectively. The deduced
      peptide of 89 amino acids consisted of 24 aa, 40 aa and 25 aa for signal peptide,
      prodomain and mature peptide, respectively. The mature peptide had eight
      cysteines at the identical conserved positions in common with most of other known
      hepcidins in vertebrates. cmHepc gene displayed a tripartite structure (three
      exons interrupted by two introns), which organisation was conserved between the
      blotched snakehead and other fish species. Phylogenetic analysis of hepcidins
      from C. maculata and other vertebrates showed that major phylogenetic grouping of
      fish hepcidin coincided with the current euteleosts classification, indicating
      the multiphyletic evolution of hepcidin in the teleosts. In the Acanthopterygii
      subclade, there were two distinct additional subclades named as HAMP-Ac1 and HAMP
      Ac2. The blotched snakehead hepcidin was in the group HAMP-Ac1, which has the
      hypothetical iron regulatory sequence [Q-S/I-H-L/I-S/A] motif in N-terminal of
      mature peptide. The RT-PCR showed cmHep mRNA transcripts were widely distributed
      in all tissues tested in the blotched snakehead including the liver, gill,
      intestine, spleen, head kidney and peripheral white blood cell. The most abundant
      of cmHep mRNA was detected in liver. A significant up-regulation of cmHep
      expression was detected only in head kidney at 24h post-challenge with Vibrio
      parahaemolyticus in blotched snakehead adults, no significant differences found
      in liver, gill, intestine and spleen. The cmHep expression was up-regulated in
      spleen, head kidney and intestine at 24h post-injection with LPS in blotched
      snakehead juveniles, liver cmHep expression was not altered. Iron overloading and
      poly I:C stimulation down-regulated cmHep expression in liver, but did not
      significantly change cmHep expression in spleen, head kidney and intestine in
      blotched snakehead juveniles.

PMID- 24287271
TI  - Acute camptocormia as the presenting symptom of tetanus.

PMID- 24287272
TI  - Generation of insulin-producing cells from rat mesenchymal stem cells using an
      aminopyrrole derivative XW4.4.
AB  - Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and
      anatomical/structural consequences, is a major health concern worldwide.
      Pancreatic islet transplantation provides a promising treatment for T1DM.
      However, the limited availability of islet tissue or new sources of insulin
      producing cells (IPCs) that are responsive to glucose hinder this promising
      approach. Though slow, the development of pancreatic beta-cell lines from rodent
      or human origin has been steadily progressing. Bone marrow-derived mesenchymal
      stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that
      are currently being investigated as a novel cellular therapy. The in vitro
      differentiation potential of IPCs has raised hopes for a treatment of clinical
      diseases associated with autoimmunity. We screened for small molecules that
      induce pancreatic differentiation of IPCs. There are some compounds which showed
      positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4
      which shows the best activity among them was found to induce pancreatic
      differentiation of rat MSCs (rMSCs). The in vitro studies indicated that
      treatment of rMSCs with compound XW4.4 resulted in differentiated cells with
      characteristics of IPCs including islet-like clusters, spherical, grape-like
      morphology, insulin secretion, positive for dithizone, glucose stimulation and
      expression of pancreatic endocrine cell marker genes. The data has also suggested
      that hepatocyte nuclear factor 3beta (HNF 3beta) may be involved in pancreatic
      differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4
      induced rMSCs support the efforts to derive functional IPCs and serve as a means
      to alleviate limitations surrounding islet cell transplantation in the treatment
      of T1DM. 

PMID- 24287273
TI  - H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS
      gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.
AB  - Helicobacter pylori encoded CagA is presently the only known virulence factor
      that is injected into gastric epithelial cells where it destroys apical
      junctional complexes and induces dedifferentiation of gastric epithelial cells,
      leading to H. pylori-related gastric carcinogensis. However, little is known
      about the molecular mechanisms by which CagA mediates these changes. Caudal
      related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly
      expressed in multistage tissues of dysplasia and cancer. One specific target of
      Cdx2, Claudin-2, is involved in the regulation of tight junction (TJ)
      permeability. In this study, our findings showed that the activity of Cdx2
      binding to Cdx binding sites of CdxA (GTTTATG) and CdxB (TTTTAGG) of probes
      corresponding to claudin-2 flanking region increased in AGS cells, infected with
      CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic
      mutant-type strain. Moreover, Cdx2 upregulated claudin-2 expression at
      transcriptional level and translational level. In the meantime, we found that TJs
      of AGS cells, infected with CagA positive wild-type strain of H. pylori, compared
      to CagA negative isogenic mutant-type strain, were more severely destroyed,
      leading to wider cell gap, interference of contact, scattering and highly
      elevated migration of cells. Herein, this study is firstly demonstrated that H.
      pylori-encoded CagA disrupts TJs and induces invasiveness of AGS gastric
      carcinoma cells via Cdx2-dependent targeting of Claudin-2. This provides a new
      mechanism whereby CagA induced dedifferentiation of AGS cells, leading to
      malignant behavior of biology.

PMID- 24287274
TI  - HCV-specific CD8+ cell detection at week 12 of chronic hepatitis C treatment with
      PEG-interferon-alpha2b/ribavirin correlates with infection resolution.
AB  - Lower than 2-log viral-load (VL) decrease at week 12 (w12) of chronic hepatitis C
      (CHC) treatment with Peg-interferon/ribavirin has 100% negative predictive value
      (PV) of sustained virologic response (SVR), and this could be related with
      absence of HCV-specific cytotoxic T lymphocyte (CTL) response. In this study,
      percentage of cases with SVR, according to peripheral HCV-specific cytotoxic
      response at w12, was analysed (Group-1: detection(+), Group-2: detection(-)). SVR
      was higher in group-1 (93%) than in group-2 (47%) (p=0.003). An increase on HCV
      specific CTL frequency between baseline and w12 and higher specific reactivity
      were observed in group-1 (p=0.011 and p=0.025). HCV-specific CTL detection at w12
      correlated with level of VL decrease (p=0.016, r=0.389), and among HCV genotype-1
      patients with either early or delayed virologic response (EDVR), 100% positive PV
      of SVR was observed. In summary, HCV-specific CTL detection at w12 of Peg
      interferon/ribavirin treatment correlates with SVR and in EDVR genotype-1 cases
      predicts SVR. 

PMID- 24287275
TI  - Are we improving disease outcomes in IBD? A view from the epidemiology side.

PMID- 24287276
TI  - In sero veritas: what serum markers teach us about HCV infection of primary human
      hepatocytes.

PMID- 24287277
TI  - Response to fibrolamellar hepatocellular carcinoma versus conventional
      hepatocellular carcinoma: better 5-year survival or artefactual result of
      research methodology?

PMID- 24287278
TI  - Endogenous NAMPT dampens chemokine expression and apoptotic responses in stressed
      tubular cells.
AB  - Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and
      identification of new therapeutic targets is needed. Nicotinamide
      phosphoribosyltransferase (NAMPT) is both an extracellular and intracellular
      protein. Circulating NAMPT is increased in diabetics and in chronic kidney
      disease patients. The role of NAMPT in renal cell biology is poorly understood.
      NAMPT mRNA and protein were increased in the kidneys of rats with streptozotocin
      induced diabetes. Immunohistochemistry localized NAMPT to glomerular and tubular
      cells in diabetic rats. The inflammatory cytokine TNFalpha increased NAMPT mRNA,
      protein and NAD production in cultured kidney human tubular cells. Exogenous
      NAMPT increased the mRNA expression of chemokines MCP-1 and RANTES. The NAMPT
      enzymatic activity inhibitor FK866 prevented these effects. By contrast, FK866
      boosted TNFalpha-induced expression of MCP-1 and RANTES mRNA and endogenous NAMPT
      targeting by siRNA also had a proinflammatory effect. Furthermore, FK866 promoted
      tubular cell apoptosis in an inflammatory milieu containing the cytokines
      TNFalpha/IFNgamma. In an inflammatory environment FK866 promoted tubular cell
      expression of the lethal cytokine TRAIL. These data are consistent with a role of
      endogenous NAMPT activity as an adaptive, protective response to an inflammatory
      milieu that differs from the proinflammatory activity of exogenous NAMPT. Thus,
      disruption of endogenous NAMPT function in stressed cells promotes tubular cell
      death and chemokine expression. This information may be relevant for the design
      of novel therapeutic strategies in DN.

PMID- 24287279
TI  - Diagnostic and therapeutic cholangiopancreatoscopy: performance of a new digital
      cholangioscope.
AB  - BACKGROUND: High-definition cholangioscopes provide excellent images of the
      pancreatobiliary ductal system and may play a significant role in diagnosis and
      treatment of various pancreatobiliary disorders. OBJECTIVE: To assess the
      performance of a new digital cholangioscope for diagnosis and treatment of
      pancreatobiliary disorders in clinical practice. DESIGN: Prospective study.
      SETTING: Academic hospital, tertiary-care referral center. PATIENTS: Consecutive
      patients with suspected pancreatobiliary disorders. INTERVENTION: Diagnostic or
      therapeutic high-definition digital cholangiopancreatoscopy. MAIN OUTCOME
      MEASUREMENTS: Satisfactory visualization of the ductal mucosa and lumen and
      treatment of pancreatobiliary disorders when indicated. RESULTS: A total of 28
      cholangioscopy and 4 pancreatoscopy procedures were completed before breakdown of
      the cholangioscope. Excellent views of the ductal lumen and mucosa were obtained
      in all patients. In the 18 patients with indeterminate biliary strictures, high
      definition cholangioscopy identified all cholangiocarcinomas but labeled as
      malignant only 1 of 4 strictures caused by pancreatic cancer (sensitivity 73%).
      All benign strictures were correctly labeled (specificity 100%). Cholangioscopy
      proved helpful in evaluation of various biliary disorders and lithotripsy of
      pancreatic stones under direct vision. LIMITATIONS: Single center, small number
      of patients. CONCLUSION: High-definition cholangioscopy is a useful adjunct to
      ERCP in the diagnosis and treatment of pancreatobiliary disorders. Although
      fragility of the cholangioscope remains a problem, the changes made in the
      construction of this prototype digital cholangioscope have significantly
      increased its durability.

PMID- 24287280
TI  - Novel single transluminal gateway transcystic multiple drainages after EUS-guided
      drainage for complicated multilocular walled-off necrosis (with videos).

PMID- 24287281
TI  - The learning curve for narrow-band imaging in the diagnosis of precancerous
      gastric lesions by using Web-based video.
AB  - BACKGROUND: A simplified narrow-band imaging (NBI) endoscopy classification of
      gastric precancerous and cancerous lesions was derived and validated in a
      multicenter study. This classification comes with the need for dissemination
      through adequate training. OBJECTIVE: To address the learning curve of this
      classification by endoscopists with differing expertise and to assess the
      feasibility of a YouTube-based learning program to disseminate it. DESIGN:
      Prospective study. SETTING: Five centers. PARTICIPANTS: Six gastroenterologists
      (3 trainees, 3 fully trained endoscopists [FTs]). INTERVENTIONS: Twenty tests
      provided through a Web-based program containing 10 randomly ordered NBI videos of
      gastric mucosa were taken. Feedback was sent 7 days after every test submission.
      MAIN OUTCOME MEASUREMENTS: Measures of accuracy of the NBI classification
      throughout the time. RESULTS: From the first to the last 50 videos, a learning
      curve was observed with a 10% increase in global accuracy, for both trainees
      (from 64% to 74%) and FTs (from 56% to 65%). After 200 videos, sensitivity and
      specificity of 80% and higher for intestinal metaplasia were observed in half the
      participants, and a specificity for dysplasia greater than 95%, along with a
      relevant likelihood ratio for a positive result of 7 to 28 and likelihood ratio
      for a negative result of 0.21 to 0.82, were achieved by all of the participants.
      No constant learning curve was observed for the identification of Helicobacter
      pylori gastritis and sensitivity to dysplasia. The trainees had better results in
      all of the parameters, except specificity for dysplasia, compared with the FTs.
      Globally, participants agreed that the program's structure was adequate, except
      on the feedback, which should have consisted of a more detailed explanation of
      each answer. LIMITATIONS: No formal sample size estimate. CONCLUSION: A Web-based
      learning program could be used to teach and disseminate classifications in the
      endoscopy field. In this study, an NBI classification for gastric mucosal
      features seems to be easily learned for the identification of gastric
      preneoplastic lesions.

PMID- 24287283
TI  - Academy of Nutrition and Dietetics 2011 survey on member research activities,
      needs, and perceptions.

PMID- 24287282
TI  - Strike a pose: Galphaq complexes at the membrane.
AB  - The heterotrimeric G protein Galphaq is a central player in signal transduction,
      relaying signals from activated G-protein-coupled receptors (GPCRs) to effectors
      and other proteins to elicit changes in intracellular Ca(2+), the actin
      cytoskeleton, and gene transcription. Galphaq functions at the intracellular
      surface of the plasma membrane, as do its best-characterized targets,
      phospholipase C-beta, p63RhoGEF, and GPCR kinase 2 (GRK2). Recent insights into
      the structure and function of these signaling complexes reveal several recurring
      themes, including complex multivalent interactions between Galphaq, its protein
      target, and the membrane, that are likely essential for allosteric control and
      maximum efficiency in signal transduction. Thus, the plasma membrane is not only
      a source of substrates but also a key player in the scaffolding of Galphaq
      dependent signaling pathways. 

PMID- 24287284
TI  - A softgel dietary supplement containing esterified plant sterols and stanols
      improves the blood lipid profile of adults with primary hypercholesterolemia: a
      randomized, double-blind, placebo-controlled replication study.
AB  - A well-controlled clinical trial previously demonstrated the efficacy of a novel
      softgel dietary supplement providing 1.8 g/day esterified plant sterols and
      stanols, as part of the National Cholesterol Education Program Therapeutic
      Lifestyle Changes diet, to improve the fasting lipid profile of men and women
      with primary hypercholesterolemia (fasting low-density lipoprotein [LDL]
      cholesterol >= 130 and <220 mg/dL [>= 3.37 and <5.70 mmol/L]). The purpose of
      this randomized, double blind, placebo-controlled crossover study (conducted July
      2011 to January 2012) was to support these previous findings in a similar, but
      independent, sample with a different lead investigator and research site.
      Repeated measures analysis of covariance was used to compare outcomes for
      sterol/stanol and placebo treatment conditions using the baseline value as a
      covariate. Forty-nine subjects were screened and 30 (8 men and 22 women) were
      randomized to treatment (all completed the trial). Baseline (mean +/- standard
      error of the mean) plasma lipid concentrations were: total cholesterol 236.6 +/-
      4.2 mg/dL (6.11 +/- 0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8
      +/- 3.0 mg/dL (1.47 +/- 0.08 mmol/L), LDL cholesterol 151.6 +/- 3.3 mg/dL (3.92
      +/- 0.09 mmol/L), non-HDL cholesterol 179.7 +/- 4.6 mg/dL (4.64 +/- 0.12 mmol/L),
      and triglycerides 144.5 +/- 14.3 mg/dL (1.63 +/- 0.16 mmol/L). Mean placebo
      adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL
      cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%),
      but not for triglycerides or HDL cholesterol. These results support the efficacy
      of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered
      as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle
      Changes diet, to augment reductions in atherogenic lipid levels in individuals
      with hypercholesterolemia.

PMID- 24287285
TI  - Use of ICD-10 codes to monitor uterine rupture: validation of a national birth
      registry.
AB  - OBJECTIVES: Uterine rupture is a rare but severe complication in pregnancies
      after a previous cesarean section. In Denmark, the monitoring of uterine rupture
      is based on reporting of relevant diagnostic codes to the Danish Medical Birth
      Registry (MBR). The aim of our study was to examine the validity of registration
      of uterine rupture in the MBR within the population of pregnant women with prior
      cesarean section by conducting a review of the medical records. STUDY DESIGN: We
      reviewed 1709 medical records within the population of singleton pregnant woman
      delivering at term between 1997 and 2007. We retrieved the medical records of all
      women in the MBR with a code for uterine rupture during labor regardless of
      whether or not a prior cesarean section had been reported to the registry. In
      addition medical records of all women with a code for previous cesarean section
      and delivery of a child with adverse perinatal outcome were retrieved. RESULTS:
      Among women recorded in the MBR with a previous cesarean section and uterine
      rupture, only 60.4% actually had a uterine rupture (partial or complete). At
      least 16.2% of complete uterine ruptures were not reported to the registry.
      Considering only complete uterine ruptures, the sensitivity and specificity of
      the codes for uterine rupture were 83.8% and 99.1%, respectively. CONCLUSION:
      During the study period the monitoring of uterine rupture in the MBR was
      inadequate.

PMID- 24287286
TI  - Invasive ultrasound in the management of cervical ectopic pregnancy.
AB  - Invasive ultrasound management of a 6-week live cervical pregnancy in a 26-year
      old primipara is described. The patient was given methotrexate three times at
      seven-day intervals with no effect. Then 15% KCl was administered intra
      amniotically via the transvaginal and transcervical route under ultrasound
      guidance. The procedure was successful, causing fetal death and loss of
      trophoblastic blood flow on Doppler examination. Over the subsequent four weeks,
      there was a steady decrease of serum beta-hCG concentration. After four weeks,
      curettage of the cervical canal and uterine cavity was performed successfully.
      This method of treatment enabled avoidance of invasive surgical procedures, which
      might have limited future fertility. 

PMID- 24287287
TI  - Pseudoaneurysm of the inferior epigastric artery after gynecological laparoscopy:
      minimally invasive management.

PMID- 24287288
TI  - Evaluation of a method of predicting lymph node metastasis in endometrial cancer
      based on five pre-operative characteristics.
AB  - OBJECTIVE: We recently developed an algorithm based on five clinical and
      pathological characteristics to predict lymph node (LN) metastasis in endometrial
      cancer. The aim of this study was to evaluate the accuracy of using this
      algorithm with preoperative characteristics. STUDY DESIGN: In this retrospective
      multicenter study, we evaluated the accuracy of using an algorithm to predict LN
      metastasis using preoperative tumor characteristics provided by endometrial
      sampling pathological characteristics (histological subtype and grade) and by
      magnetic resonance imaging (MRI) for primary site tumor extension. RESULTS: In
      total, 181 patients were included in this study, and 14 patients had pelvic LN
      metastasis (7.7%). Using preoperative tumor characteristics, the algorithm showed
      good discrimination with an area under the receiver operating characteristic
      curve (AUC) of 0.83 (95% confidence interval (IC95)=0.79-0.87) and was well
      calibrated (average error=1.9% and maximal error=8.5%). LN metastasis prediction
      by the algorithm using preoperative data was as accurate as that obtained using
      the final tumor characteristics (AUC=0.77 (CI95=0.70-0.83), average error=2.8%
      and maximal error=23.2%). CONCLUSION: Our algorithm was accurate in predicting
      pelvic LN metastasis even with the use of preoperative tumor characteristics
      provided by endometrial sampling and MRI. These findings, however, should be
      verified in a larger database before our algorithm is implemented for widespread
      use.

PMID- 24287289
TI  - Dyspareunia and quality of sex life after surgical excision of endometriosis: a
      systematic review.
AB  - Dyspareunia, a common symptom of endometriosis, severely affects quality of sex
      life in affected women. The objective of the present work was to review the
      effect of surgical resection of endometriosis on pain intensity and quality of
      sex life. MEDLINE and EMBASE databases were searched for papers investigating the
      outcome after surgical endometriosis resection on dyspareunia and quality of sex
      life measured via VAS/NAS respectively via standardised measuring instruments.
      Data did not permit a meaningful meta-analysis. Out of 64 papers, three studies
      fulfilled the predefined inclusion criteria involving 128 patients with
      endometriosis and dyspareunia preoperatively. All included studies showed a
      significant postoperative reduction (p<0.05) of dyspareunia after a follow-up
      period of 12 up to 60 months. Sex life also improved significantly (p<0.05), and
      predominantly evaluated parameters like quality of life and mental health. Intra-
      and postoperative complications were described in two out of three studies.
      Surgical excision of deep infiltrating endometriosis is feasible and improves
      dyspareunia and quality of sex life significantly. 

PMID- 24287290
TI  - The cell cycle arrest and the anti-invasive effects of nitrogen-containing
      bisphosphonates are not mediated by DBF4 in breast cancer cells.
AB  - Recent work has shown that a DBF4 analog in yeast may be a target of nitrogen
      containing bisphosphonates. DBF4 is an essential protein kinase required for DNA
      replication from primary eukaryotes to humans and appears to play a critical role
      in the S-phase checkpoint. It is also required for cell migration and cell
      surface adhesion. The effects of Pamidronate, risedronate, or zoledronate on cell
      viability and DBF4 expression were measured via MTT assays and western blotting.
      In addition, FACS cell cycle analyses and invasion assays were conducted in cells
      in the presence of nitrogen-containing bisphosphonates to identify any
      correlations between DBF4 expression and S-phase arrest or anti-invasive effects
      of the bisphosphonates. Zoledronate transiently down-regulated DBF4 expression in
      all three cell lines in the first 24 h of the experiment, but after 72 h, DBF4
      expression returned to the control levels in all treated cells. Following
      treatment of the tumor cells with the bisphosphonates, the number of cells in S
      phase was increased. Pamidronate and zoledronate showed anti-invasive effects in
      BT20 cells. The anti-invasive effects of pamidronate, risedronate and zoledronate
      appeared after 48 h of exposure. In MDA-MB231 cells a reduction of invasiveness
      was only observed after 72 h of the pamidronate exposure. We finally concluded
      that the anti-invasive and cell cycle arrest-inducing effects of nitrogen
      containing bisphosphonates are not DBF4 mediated, and other mediators are
      therefore needed to explain the observed complex behaviors. 

PMID- 24287291
TI  - The effect of group X secreted phospholipase A2 on fertilization outcome is
      specific and not mimicked by other secreted phospholipases A2 or progesterone.
AB  - Mouse group X sPLA2 (mGX) is an acrosomal protein playing an important role in
      fertilization and controlling acrosome reaction (AR) occurring during
      capacitation. We demonstrated previously that sperm from mGX knock-out mice had a
      severely impaired fertilization potential in vitro. We also showed that treatment
      of wild-type sperm with recombinant mGX during capacitation improved
      fertilization outcome. This interesting property suggests that sPLA2s could be
      used to improve fertilization in assisted reproductive technologies (ART).
      However the molecular mechanism explaining the mGX-dependent enhancing effect on
      fertilization outcome remains unclear so far. Interestingly, like progesterone
      (P4), mGX is a very potent activator of AR and the role of mGX-induced AR in
      fertilization outcome was not evaluated so far. To assess the role of sPLA2
      induced AR in IVF, we first tested the potency of 9 mouse and 2 human sPLA2s and
      P4 to trigger AR of mouse sperm. We then tested the ability of 6 of these
      molecules (mouse Group IIA, mouse Group IID, mouse Group X, human Group V, human
      Group X and P4) to improve the yield of 2-cell embryos obtained by IVF in mouse.
      We showed that in the mouse neither P4 nor any of the other sPLA2s tested were
      able to mimic the IVF improvement produced by mGX-treatment. These results
      demonstrate that sPLA2s are not commutable in the context of mouse sperm
      fertility, indicating that their utilisation in other species, is subjected to
      the identification of probably unique species-specific active sPLA2. 

PMID- 24287292
TI  - Endothelial PKCalpha-MAPK/ERK-phospholipase A2 pathway activation as a response
      of glioma in a triple culture model. A new role for pericytes?
AB  - In view of understanding the molecular mechanisms through which angiogenic switch
      on happens in the early phases of reciprocal interaction between tumor and cells
      constituting microvessel, a triple culture model in which endothelial cells (EC),
      pericytes (PC) and glioma C6 cells were cultured together. In the present work,
      we observed that C6 enhanced EC proliferation. This effect was reduced by
      cytosolic and Ca(2+)-independent phospholipase A2 (cPLA2 and iPLA2),
      cyclooxygenase-2 (COX-2), PI3-K, MEK-1, and ERK1/2 inhibitors and by siRNAs
      against both PLA2s. In EC, C6 induced an increase in iPLA2, cPLA2 and COX-2 total
      protein expression. Moreover, the increase in endothelial cPLA2 phosphorylation
      was attenuated by kinase inhibitors. Both EC proliferation and signal protein
      phosphorylation were attenuated when PC were in triple culture. In EC/C6
      supernatants, and, in a lesser extent, in EC/PC co-cultures, an enhancement in
      prostaglandins E2 (PGE2) was found. The presence of PC in triple-cultures caused
      a decrease in production of PGE2 respect to EC/C6 double-cultures. In all
      systems, AACOCF3 and BEL significantly reduced PGE2 secretion. In Matrigel-based
      assays, emerging branch points from EC cell bodies and tubule-like structures
      were observed. C6 conditioned EC/PC co-cultures in constituting poorly organized
      tubules. Transfection of EC with c- and iPLA2 siRNA strongly reduced in vitro
      tubulogenesis. Data here reported indicate that PKCalpha, ERK kinase
      phosphorylation, PLA2s and COX-2 activation, and PGE2 production in EC stimulated
      by tumor cells are coincident phenomena and could represent therapeutic targets
      in chemoprevention of glioma. Moreover, PC exhibited an important "modulating"
      role in the initial stages of angiogenesis driven by a brain tumor. 

PMID- 24287293
TI  - Disturbances in cholesterol, bile acid and glucose metabolism in peroxisomal 3
      ketoacylCoA thiolase B deficient mice fed diets containing high or low fat
      contents.
AB  - The peroxisomal 3-ketoacyl-CoA thiolase B (ThB) catalyzes the thiolytic cleavage
      of straight chain 3-ketoacyl-CoAs. Up to now, the ability of ThB to interfere
      with lipid metabolism was studied in mice fed a laboratory chow enriched or not
      with the synthetic agonist Wy14,643, a pharmacological activator of the nuclear
      hormone receptor PPARalpha. The aim of the present study was therefore to
      determine whether ThB could play a role in obesity and lipid metabolism when mice
      are chronically fed a synthetic High Fat Diet (HFD) or a Low Fat Diet (LFD) as a
      control diet. To investigate this possibility, wild-type (WT) mice and mice
      deficient for Thb (Thb(-/-)) were subjected to either a synthetic LFD or a HFD
      for 25 weeks, and their responses were compared. First, when fed a normal
      regulatory laboratory chow, Thb(-/-) mice displayed growth retardation as well as
      a severe reduction in the plasma level of Growth Hormone (GH) and Insulin Growth
      Factor-I (IGF-I), suggesting alterations in the GH/IGF-1 pathway. When fed the
      synthetic diets, the corrected energy intake to body mass was significantly
      higher in Thb(-/-) mice, yet those mice were protected from HFD-induced
      adiposity. Importantly, Thb(-/-) mice also suffered from hypoglycemia, exhibited
      reduction in liver glycogen stores and circulating insulin levels under the LFD
      and the HFD. Thb deficiency was also associated with higher levels of plasma HDL
      (High Density Lipoproteins) cholesterol and increased liver content of
      cholesterol under both the LFD and the HFD. As shown by the plasma lathosterol to
      cholesterol ratio, a surrogate marker for cholesterol biosynthesis, whole body
      cholesterol de novo synthesis was increased in Thb(-/-) mice. By comparing liver
      RNA from WT mice and Thb(-/-) mice using oligonucleotide microarray and RT-qPCR,
      a coordinated decrease in the expression of critical cholesterol synthesizing
      genes and an increased expression of genes involved in bile acid synthesis
      (Cyp7a1, Cyp17a1, Akr1d1) were observed in Thb(-/-) mice. In parallel, the
      elevation of the lathosterol to cholesterol ratio as well as the increased
      expression of cholesterol synthesizing genes were observed in the kidney of Thb(
      /-) mice fed the LFD and the HFD. Overall, the data indicate that ThB is not
      fully interchangeable with the thiolase A isoform. The present study also reveals
      that modulating the expression of the peroxisomal ThB enzyme can largely
      reverberate not only throughout fatty acid metabolism but also cholesterol, bile
      acid and glucose metabolism. 

PMID- 24287294
TI  - A generic model for spoilage of acidic emulsified foods: combining
      physicochemical data, diversity and levels of specific spoilage organisms.
AB  - The spoilage pattern of three emulsified, vegetable-based spreads of low pH (3.90
      4.15) adjusted with acetic acid was characterized by correlating the growth of
      spoilage flora with the organoleptic and physicochemical changes, as well as the
      changes in the species composition of the dominant microflora during storage
      under isothermal conditions. In a further step, a generic (hereafter called
      'unified') model was developed to describe the maximum specific growth rate of
      the specific spoilage organisms (SSOs) in all acetic acid acidified products,
      including literature data and additional in-house data from similar products, as
      a function of the storage temperature, pH (3.61-4.25) and initial concentration
      of the undissociated acetic acid in each product. The predictions of the unified
      model were compared with those of product-specific models, with temperature as
      the sole predictor variable. Two independent batches of commercially prepared
      pepper- (PS), fava beans- (FS) and eggplant-based (ES) spreads were stored at 4,
      7, 10, 12, 15, 18, 20 and 25 degrees C. The growth of lactic acid bacteria (SSOs;
      LAB) was correlated with changes in pH, titratable acidity and organic acids
      concentration, as well as sensory characteristics, in order to define the shelf
      life of the products. Isolates from each spread and storage temperature were
      grouped with SDS-PAGE and were identified with 16S rRNA, determining the
      association between spoilage and species diversity. Product-specific models were
      developed using the square root model, while a polynomial and the Ratkowsky model
      were used for the development of the unified model. Products with lower pH and/or
      higher acetic acid content showed higher microbial stability. Lactobacillus
      plantarum or Lactobacillus brevis dominated the LAB association in all three
      spreads, although their relative percentage at the beginning of storage varied
      significantly. These facultative or obligate hetero-fermentative bacteria
      increased lactic acid and, sporadically, acetic acid levels in the spreads. The
      developed models were validated under real chill chain conditions and showed very
      good agreement with the observed data in PS and FS. The spoilage perception
      patterns of the different products were similar and thus, the proposed unified
      model may provide accurate predictions for the spoilage of a wide variety of
      acetic acid-acidified spreads, regardless of differences in the formulation
      (e.g., raw materials) and the manufacturing procedure. 

PMID- 24287295
TI  - Impact of addition of aromatic amino acids on non-volatile and volatile compounds
      in lychee wine fermented with Saccharomyces cerevisiae MERIT.ferm.
AB  - The impact of individual aromatic amino acid addition (L-phenylalanine, L
      tryptophan and L-tyrosine) on non-volatile and volatile constituents in lychee
      wine fermented with Saccharomyces cerevisiae var. cerevisiae MERIT.ferm was
      studied. None of the added amino acids had any significant effect on the yeast
      cell count, pH, soluble solid contents, sugars and ethanol. The addition of L
      phenylalanine significantly reduced the production of pyruvic and succinic acids.
      The addition of each amino acid dramatically reduced the consumption of proline
      and decreased the production of glycerol. Supplementation of the lychee juice
      with L-phenylalanine resulted in the formation of significantly higher amounts of
      2-phenylethyl alcohol, 2-phenylethyl acetate, 2-phenylethyl isobutyrate and 2
      phenylethyl hexanoate. In contrast, supplementation with L-tryptophan and L
      tyrosine had negligible effects on the volatile profile of lychee wines. These
      findings suggest that selectively adding amino acids may be used as a tool to
      modulate the volatile profile of lychee wines so as to diversify and/or intensify
      wine flavour and style.

PMID- 24287296
TI  - Being 'rational' and being 'human': How National Health Service rationing
      decisions are constructed as rational by resource allocation panels.
AB  - The English National Health Service Constitution states that patients have the
      right to expect all decisions about access to medicines and treatments to be made
      'rationally'. Rationality in health care can be framed as instrumental,
      institutional or practical. In this article, we present a case example from an
      ethnographic study of the work of 'Individual Funding Request' panels to explore
      how rationality is enacted and accounted for in deliberations about the rationing
      of health care in the National Health Service. Our rhetorical analysis highlights
      how an embodied, practical rationality emerges as a significant aspect of
      rationality in practice, but at the same time has a problematic status in formal
      accounts of decision-making. We suggest that being both 'human' and 'rational' is
      a 'delicate balance' and creates a dilemma for Individual Funding Request panels.
      Aristotle's notion of phronesis provides a useful lens for theorising our
      observation of panel deliberations, and we argue for greater attention to the
      value of narrative ethics in helping us understand the challenges faced by
      resource allocators. 

PMID- 24287297
TI  - The merit of sociological accounts of disorder: The Attention-Deficit
      Hyperactivity Disorder case.
AB  - This article argues in favor of a sociological perspective on health and illness,
      drawing on recognized positions from the philosophy of health and illness about
      how to demarcate disorder from non-disorder. The argument specifies that a
      normative context in which bodies or behaviors are disvalued is a necessary
      component for identifying what constitutes a disorder, as this normative context
      allows material differences to be understood as dysfunctional and pathological.
      Descriptions of material states in themselves are insufficient to distinguish
      what is legitimately a disorder; some evaluative stance toward those states is
      also required. This article applies the argument to disorders of inattention and
      hyperactivity, currently best known as Attention-Deficit Hyperactivity Disorder.
      These disorders have been controversial since their formalization in the 1970s,
      the same time that they began receiving sociological attention. Sociological
      analyses have consistently expressed ambivalence toward recognizing claims about
      the biological status of such disorders. This ambivalence has at times committed
      to a problematic relationship between sociological explanation and medical
      explanation, implicitly allocating sociological explanation to an auxiliary
      position. This article argues that this is not necessary, as sociological
      perspectives address disorders on a fundamental, rather than secondary, register.
      Disorders are only intelligible due to the normative and social context in which
      they are found, and so medical sociology can recognize the validity of biological
      claims about disorders, such as Attention-Deficit Hyperactivity Disorder, while
      still asserting the essential social nature of disorder. 

PMID- 24287298
TI  - Anti-normative lifestyles in cardiac rehabilitation: Underprivileged men's post
      heart incident lives.
AB  - Cardiovascular diseases are leading causes of premature mortality and disability.
      Although health institutions have developed and promoted cardiac rehabilitation
      programs, they have not attained their desired outcomes, especially among the
      most vulnerable groups of the population. This study qualitatively examines
      socially and materially deprived men's (n = 20) noncompliance with cardiovascular
      health guidelines following a medical intervention to the heart. By drawing on
      Pierre Bourdieu's sociocultural theory of practice, results indicate that
      precarious living conditions obstruct long-term physical recovery and illness
      prevention by underemphasizing the value of "health capital" and reducing the
      capacity to sustain lifestyle change. This study calls into question health
      policies that have little to no consideration of embodied practical knowledge and
      lived experiences. 

PMID- 24287299
TI  - Non-biodegradable landfill leachate treatment by combined process of agitation,
      coagulation, SBR and filtration.
AB  - This study describes the complete treatment of non-biodegradable landfill
      leachate by combined treatment processes. The processes consist of agitation as a
      novel stripping method used to overcome the ammonia toxicity regarding aerobic
      microorganisms. The NH3-N removal ratio was 93.9% obtained at pH 11.5 and a
      gradient velocity (G) 150 s(-1) within a five-hour agitation time. By poly ferric
      sulphate (PFS) coagulation followed the agitation process; chemical oxygen demand
      (COD) and biological oxygen demand (BOD5) were removed at 70.6% and 49.4%,
      respectively at an optimum dose of 1200 mg L(-1) at pH 5.0. The biodegradable
      ratio BOD5/COD was improved from 0.18 to 0.31 during pretreatment step by
      agitation and PFS coagulation. Thereafter, the effluent was diluted with sewage
      at a different ratio before it was subjected to sequencing batch reactor (SBR)
      treatment. Up to 93.3% BOD5, 95.5% COD and 98.1% NH3-N removal were achieved by
      SBR operated under anoxic-aerobic-anoxic conditions. The filtration process was
      carried out using sand and carbon as a dual filter media as polishing process.
      The final effluent concentration of COD, BOD5, suspended solid (SS), NH3-N and
      total organic carbon (TOC) were 72.4 mg L(-1), 22.8 mg L(-1), 24.2 mg L(-1), 18.4
      mg L(-1) and 50.8 mg L(-1) respectively, which met the discharge standard. The
      results indicated that a combined process of agitation-coagulation-SBR and
      filtration effectively eliminated pollutant loading from landfill leachate.

PMID- 24287300
TI  - The financial and economic feasibility of rural household biodigesters for poor
      communities in South Africa.
AB  - Given the persistence of systemic poverty in, most notably, the rural parts of
      South Africa, the question is whether the use of biodigesters as a source of
      energy offers potential solutions to some of the difficulties and development
      needs faced by people in these areas. At the core, this translates into whether
      this technology would be financially and economically feasible for installation
      and use by rural households. Here we conduct both a financial and an economic
      cost-benefit analysis in one such community based on survey data from 120
      households. Analysis of these data and supporting literature reveals that a
      biodigester is not a financially feasible investment for a rural household.
      Substantial economic benefits are, however, found to make a biodigester a
      worthwhile investment from a broader societal perspective. This is a compelling
      argument for further study and the consideration of government support in the
      light of broader economy-wide benefits. 

PMID- 24287301
TI  - Still in pursuit.

PMID- 24287302
TI  - A new comorbidity model for predicting mortality in patients with cirrhosis: does
      it work?

PMID- 24287303
TI  - Role of dietary FODMAPs in IBS-related symptoms.

PMID- 24287304
TI  - Dating human skeletal remains using 90Sr and 210Pb: case studies.
AB  - In legal medicine, the post mortem interval (PMI) of interest covers the last 50
      years. When only human skeletal remains are found, determining the PMI currently
      relies mostly on the experience of the forensic anthropologist, with few
      techniques available to help. Recently, several radiometric methods have been
      proposed to reveal PMI. For instance, (14)C and (90)Sr bomb pulse dating covers
      the last 60 years and give reliable PMI when teeth or bones are available.
      (232)Th series dating has also been proposed but requires a large amount of
      bones. In addition, (210)Pb dating is promising but is submitted to diagenesis
      and individual habits like smoking that must be handled carefully. Here we
      determine PMI on 29 cases of forensic interest using (90)Sr bomb pulse. In 12
      cases, (210)Pb dating was added to narrow the PMI interval. In addition,
      anthropological investigations were carried out on 15 cases to confront
      anthropological expertise to the radiometric method. Results show that 10 of the
      29 cases can be discarded as having no forensic interest (PMI>50 years) based
      only on the (90)Sr bomb pulse dating. For 10 other cases, the additional (210)Pb
      dating restricts the PMI uncertainty to a few years. In 15 cases, anthropological
      investigations corroborate the radiometric PMI. This study also shows that
      diagenesis and inter-individual difference in radionuclide uptake represent the
      main sources of uncertainty in the PMI determination using radiometric methods.

PMID- 24287305
TI  - Determination of optimal conditions for 5-methyl-benzotriazole biodegradation
      with activated sludge communities by dilution of the inoculum.
AB  - The aerobic biodegradation of 5-methyl-benzotriazole (5-TTri) was optimized using
      lab-scale setups and activated sludge communities (ASC) collected from three
      wastewater treatment plants (WWTP) MBR-MH, CAS-E and CAS-M being different in
      their treatment technologies. ASC inocula were diluted to rule out non
      biodegrading species and incubated under two nutrient conditions: A) mineral salt
      media (MSM) and B) carbon and nitrogen supplied MSM giving MSM-CN. 5-TTri removal
      with the ASC ranged from 60% to 100% in only 10 days. 100 MUL suspended biomass
      from the biodegrading setups was subsequently plated on solid media to eliminate
      possible activated sludge remnants. After growth occurred, mixed colonies were
      harvested and inoculated in fresh liquid MSM containing 20 mg L(-1) 5-TTri. These
      bacterial consortia showed good 5-TTri removal in MSM-CN rather than in MSM,
      indicating nutrient supply being required for efficient biodegradation. In
      addition, experiments with high 5-TTri concentrations ranging from 20 to 1,000 mg
      L(-1) were conducted in both, MSM and MSM-CN and the maximal 5-TTri removal
      capacity of the ASC evaluated. 50 mg L(-1) 5-TTri was still removed in both media
      whereas 100 mg L(-1) was solely removed in MSM-CN. 5-TTri biodegradation patterns
      also indicated that 5-TTri might be co-metabolized by microbial consortia.
      Furthermore, experiments with gradient-solid-media-plates showed 5-TTri to be
      inhibitory for the ASC in concentrations above 50 mg L(-1) and revealed the
      optimal conditions regarding carbon and nitrogen concentration and pH value for
      effective 5-TTri biodegradation by ASC. Nitrogen proved a crucial factor for
      enhancing organisms' biodegradation capacity with an optimal pH around 7 while
      carbon showed no such effect.

PMID- 24287306
TI  - Intrinsic viscoelasticity increases temperature in knee cartilage under
      physiological loading.
AB  - Metabolism of proteoglycans and hyaluronic acid has been shown to be temperature
      dependent in cartilage explants, with optimal anabolic effects between 36 degrees
      C and 38 degrees C. At rest, the temperature of human knee has a value of around
      33 degrees C. We aim to show in this study that viscoelastic properties of
      healthy human cartilage allow its temperature to reach those optimal temperatures
      during physiological mechanical loadings. We developed a model allowing to
      determine the temperature increase in cartilage due to viscous dissipation. The
      model had three parameters, which were determined experimentally. The first
      parameter was the energy dissipated by cartilage samples submitted to cyclic
      stimulation. It was obtained with standard in vitro mechanical testing. The
      second parameter was the cartilage heat capacity and was measured in vitro with
      differential scanning calorimetry. Finally, the third parameter was the time
      constant of cartilage heat transfer and was obtained with in vivo magnetic
      resonance thermometry performed on four volunteers. With these experimentally
      determined parameters, the model predicted that cartilage dissipation is
      sufficient to raise the temperature in healthy knee cartilage from 33 degrees C
      to 36.7 degrees C after a 1h walking. These results showed that intrinsic
      viscoelastic properties of the cartilage could induce a temperature increase
      optimal for the production of proteoglycans and hyaluronic acid. Interestingly,
      degenerated cartilage did not present high enough viscoelastic properties to
      significantly induce a temperature increase. Taken together, these data suggest
      an association between cartilage dissipation and its homeostasis. 

PMID- 24287307
TI  - Effect of cryogenic treatment on wear resistance of Ti-6Al-4V alloy for
      biomedical applications.
AB  - The effect of cryogenic treatment on wear resistance of Ti-6Al-4V alloy for
      biomedical applications was experimentally investigated in this paper. Cryogenic
      treatments with the same soaking time of 24h at different temperatures of -80
      degrees C, -140 degrees C and -196 degrees C were conducted and the treatments at
      the same temperature of -196 degrees C were then further given different soaking
      time of 3h, 48h and 72h to be investigated. After cryogenic treatment, the
      Vickers hardness of specimens was measured. Wear resistance of Ti-6Al-4V alloy
      was measured by pin-on-disk wear test under dry sliding condition. The results
      demonstrated that the Vickers hardness increased slightly with the reduction of
      temperature while it increased obviously with the elongation of soaking time at 
      196 degrees C. The friction coefficients of specimens cryo-treated at -196
      degrees C were lower than those of untreated and of cryo-treated at -80 degrees C
      and -140 degrees C. And the longer the soaking time is during the cryogenic
      treatment, the higher the friction coefficient reduction can be achieved. The
      obvious reduction of mass loss can be obtained at -196 degrees C with 72h
      soaking. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) were
      used to detect the microstructure and worn surface of specimens. By cryogenic
      treatment, the plowing in the worn surface was smoothed and shallowed, and the
      degree of plastic deformation in the subsurface was decreased. There was no
      obvious phase transformation which can be detected in the microstructure after
      cryogenic treatment. However, the tendency of refinement in grain size can be
      detected by XRD which improved the wear resistance of Ti-6Al-4V alloy. 

PMID- 24287309
TI  - The elusive engram: what can infantile amnesia tell us about memory?
AB  - Revealing the engram is one of the greatest challenges in neuroscience. Many
      researchers focus on understanding the cellular and molecular mechanisms
      underlying the formation and maintenance of the engram, but an underutilized
      approach has been to investigate analogous processes associated with forgetting.
      Infant rodents present an ideal model for this purpose because they display a
      rapid form of non-pathological forgetting known as infantile amnesia (IA).
      Despite the widespread importance of this interesting phenomenon, the study of
      the neural bases of IA has remained largely neglected. Here, we consider what IA
      can tell us about memory. We argue that to understand the mechanisms underlying
      the engram we must also gain an appreciation of the mechanisms that drive
      forgetting. 

PMID- 24287308
TI  - Measuring and using light in the melanopsin age.
AB  - Light is a potent stimulus for regulating circadian, hormonal, and behavioral
      systems. In addition, light therapy is effective for certain affective disorders,
      sleep problems, and circadian rhythm disruption. These biological and behavioral
      effects of light are influenced by a distinct photoreceptor in the eye,
      melanopsin-containing intrinsically photosensitive retinal ganglion cells
      (ipRGCs), in addition to conventional rods and cones. We summarize the
      neurophysiology of this newly described sensory pathway and consider implications
      for the measurement, production, and application of light. A new light
      measurement strategy taking account of the complex photoreceptive inputs to these
      non-visual responses is proposed for use by researchers, and simple suggestions
      for artificial/architectural lighting are provided for regulatory authorities,
      lighting manufacturers, designers, and engineers. 

PMID- 24287311
TI  - Remnant cholesterol as a cause of ischemic heart disease: evidence, definition,
      measurement, atherogenicity, high risk patients, and present and future
      treatment.
AB  - This review focuses on remnant cholesterol as a causal risk factor for ischemic
      heart disease (IHD), on its definition, measurement, atherogenicity, and levels
      in high risk patient groups; in addition, present and future pharmacological
      approaches to lowering remnant cholesterol levels are considered. Observational
      studies show association between elevated levels of remnant cholesterol and
      increased risk of cardiovascular disease, even when remnant cholesterol levels
      are defined, measured, or calculated in different ways. In-vitro and animal
      studies also support the contention that elevated levels of remnant cholesterol
      may cause atherosclerosis same way as elevated levels of low-density lipoprotein
      (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic
      studies of variants associated with elevated remnant cholesterol levels show that
      an increment of 1mmol/L (39mg/dL) in levels of nonfasting remnant cholesterol
      associates with a 2.8-fold increased risk of IHD, independently of high-density
      lipoprotein cholesterol levels. Results from genetic studies also show that
      elevated levels of remnant cholesterol are causally associated with both low
      grade inflammation and IHD. However, elevated levels of LDL cholesterol are
      associated with IHD, but not with low-grade inflammation. Such results indicate
      that elevated LDL cholesterol levels cause atherosclerosis without a major
      inflammatory component, whereas an inflammatory component of atherosclerosis is
      driven by elevated remnant cholesterol levels. Post-hoc subgroup analyses of
      randomized trials using fibrates in individuals with elevated triglyceride
      levels, elevated remnant cholesterol levels, show a benefit of lowering
      triglycerides or remnant cholesterol levels; however, large randomized trials
      with the primary target of lowering remnant cholesterol levels are still missing.

PMID- 24287312
TI  - p53 in neurodegenerative diseases and brain cancers.
AB  - More than thirty years elapsed since a protein, not yet called p53 at the time,
      was detected to bind SV40 during viral infection. Thousands of papers later, p53
      evolved as the main tumor suppressor involved in growth arrest and apoptosis. A
      lot has been done but the protein has not yet revealed all its secrets.
      Particularly important is the observation that in totally distinct pathologies
      where apoptosis is either exacerbated or impaired, p53 appears to play a central
      role. This is exemplified for Alzheimer's and Parkinson's diseases that represent
      the two main causes of age-related neurodegenerative affections, where cell death
      enhancement appears as one of the main etiological paradigms. Conversely, in
      cancers, about half of the cases are linked to mutations in p53 leading to the
      impairment of p53-dependent apoptosis. The involvement of p53 in these
      pathologies has driven a huge amount of studies aimed at designing chemical tools
      or biological approaches to rescue p53 defects or over-activity. Here, we
      describe the data linking p53 to neurodegenerative diseases and brain cancers,
      and we document the various strategies to interfere with p53 dysfunctions in
      these disorders. 

PMID- 24287310
TI  - O-GlcNAc and the cardiovascular system.
AB  - The cardiovascular system is capable of robust changes in response to physiologic
      and pathologic stimuli through intricate signaling mechanisms. The area of
      metabolism has witnessed a veritable renaissance in the cardiovascular system. In
      particular, the post-translational beta-O-linkage of N-acetylglucosamine (O
      GlcNAc) to cellular proteins represents one such signaling pathway that has been
      implicated in the pathophysiology of cardiovascular disease. This highly dynamic
      protein modification may induce functional changes in proteins and regulate key
      cellular processes including translation, transcription, and cell death. In
      addition, its potential interplay with phosphorylation provides an additional
      layer of complexity to post-translational regulation. The hexosamine biosynthetic
      pathway generally requires glucose to form the nucleotide sugar, UDP-GlcNAc.
      Accordingly, O-GlcNAcylation may be altered in response to nutrient availability
      and cellular stress. Recent literature supports O-GlcNAcylation as an
      autoprotective response in models of acute stress (hypoxia, ischemia, oxidative
      stress). Models of sustained stress, such as pressure overload hypertrophy, and
      infarct-induced heart failure, may also require protein O-GlcNAcylation as a
      partial compensatory mechanism. Yet, in models of Type II diabetes, O
      GlcNAcylation has been implicated in the subsequent development of vascular, and
      even cardiac, dysfunction. This review will address this apparent paradox and
      discuss the potential mechanisms of O-GlcNAc-mediated cardioprotection and
      cardiovascular dysfunction. This discussion will also address potential targets
      for pharmacologic interventions and the unique considerations related to such
      targets. 

PMID- 24287313
TI  - The ocular renin-angiotensin system: a therapeutic target for the treatment of
      ocular disease.
AB  - The renin-angiotensin system (RAS) is most well-known for its role in regulation
      and dysregulation of blood pressure as well as fluid and electrolyte homeostasis.
      Due to its ability to cause cardiovascular disease, the RAS is the target of a
      multitude of drugs that antagonize its pathophysiological effects. While the
      "classical" RAS is a systemic hormonal system, there is an increasing awareness
      of the existence and functional significance of local RASs in a number of organs,
      e.g., liver, kidney, heart, lungs, reproductive organs, adipose tissue and
      adrenal. The eye is one of these organs where a compelling body of evidence has
      demonstrated the presence of a local RAS. Individual components of the RAS have
      been shown to be present in many structures of the eye and their potential
      functional significance in ocular disease states is described. Because the eye is
      one of the most important and complex organs in the body, this review also
      discusses the implications of dysregulation of the systemic RAS on the
      pathogenesis of ocular diseases and how pharmacological manipulation of the RAS
      might lead to novel or adjunctive therapies for ocular disease states. 

PMID- 24287314
TI  - Development of a modified straw method for vitrification of in vitro-produced
      bovine blastocysts and various genes expression in between the methods.
AB  - This study evaluated a modified plastic straw loading method for vitrification of
      in vitro-produced bovine blastocysts. A modified straw was used with a depressed
      area on its inner surface to which embryos attach. In vitro-produced blastocysts
      were randomly assigned into three groups: (i) blastocysts attached to the inner
      surface of a plastic straw (aV), (ii) blastocysts attached to the inner surface
      of a modified plastic straw (maV), and (iii) non-vitrified blastocysts (control).
      The recovery rates were not significantly different between aV and maV groups
      (95.8% vs. 94.3%). The post-thaw survival rate did not significantly differ
      between aV and maV groups (86.4% vs. 88.2%). The total cell numbers of blastocyst
      was higher in control than in aV and maV groups (142 +/- 21.8 vs. 117 +/- 29.7
      and 120 +/- 25.2; P < 0.05), but not significantly differ between aV and maV
      groups. The mRNA levels of pro-apoptosis related genes Bax and Caspase-3 were
      higher in aV and maV than in control (P < 0.05). By contrast, the mRNA levels of
      anti-apoptotic genes Bcl-2 and Mcl-1 and of antioxidant-related genes MnSOD and
      Prdx5 were lower in aV and maV than in control (P < 0.05). Confocal microscopy
      analysis of Golgi apparatus and mitochondria showed that the fluorescence
      intensity of Golgi apparatus and mitochondria was higher in control than in aV
      and maV groups. In conclusion, both aV and maV methods can be used to
      successfully vitrify IVP blastocysts, with maV method to be preferable because of
      its easiness in embryo loading.

PMID- 24287315
TI  - Suppression of voluntary wheel running in rats is dependent on the site of
      inflammation: evidence for voluntary running as a measure of hind paw-evoked
      pain.
AB  - Decreased voluntary wheel running has recently been proposed as a preclinical
      pain measure for inflammatory pain, but whether this reflects pain evoked by use
      of the affected limbs is unknown. To assess the role of inflammation site as a
      determinant of this measure, complete Freund's adjuvant (CFA), formalin, or
      equivolume vehicle was subcutaneously injected into the plantar surface of the
      hind paws (bilateral) or L1 dorsum dermatome (leaving paws unaffected) of male
      Sprague Dawley rats. CFA-induced hind paw mechanical allodynia (P < .001) did not
      correlate with reduced voluntary wheel running. Intraplantar formalin did not
      attenuate voluntary running, despite eliciting robust licking/writhing/flinching
      behavior and hind paw mechanical allodynia (P < .001). Subcutaneous L1 dorsum
      dermatome formalin, but not CFA, induced licking/writhing/flinching behavior (P <
      .001), but neither induced hind paw mechanical allodynia or attenuated voluntary
      running. That voluntary running is decreased by hind paw CFA, but not by L1
      dorsum CFA, implies that the behavior is a measure of CFA-induced pain evoked by
      use of the affected limbs rather than supraspinal pain processing that is
      independent of inflammation site. Furthermore, the results suggest that
      interpretation of voluntary wheel running data cannot simply be explained by
      correlation with mechanical allodynia. PERSPECTIVE: Whether decreased voluntary
      running is dependent on inflammation site is unknown. We show that intraplantar,
      but not L1 dorsum, CFA suppressed voluntary running and formalin-induced
      licking/writhing/flinching behavior but had no effect on voluntary running. These
      data suggest that suppressed voluntary running by CFA likely reflects pain evoked
      by use of the affected limbs.

PMID- 24287316
TI  - Robotic kidney transplantation with regional hypothermia: evolution of a novel
      procedure utilizing the IDEAL guidelines (IDEAL phase 0 and 1).
AB  - BACKGROUND: Surgical innovation is essential for progress of surgical science,
      but its implementation comes with potential harms during the learning phase. The
      Balliol Collaboration has recommended a set of guidelines (Innovation,
      Development, Exploration, Assessment, Long-term study [IDEAL]) that permit
      innovation while minimizing complications. OBJECTIVE: To utilize the IDEAL model
      of surgical innovation in the development of a novel surgical technique, robotic
      kidney transplantation (RKT) with regional hypothermia, and describe the process
      of discovery and development. DESIGN, SETTING, AND PARTICIPANTS: Phase 0
      (simulation) studies included the establishment of techniques for pelvic cooling,
      graft placement in a robotic prostatectomy model, and simulation of the RKT
      procedure in a cadaveric model. Phase 1 (innovation) studies began in January
      2013 and involved treatment of a highly selective small group of patients (n=7),
      using the principles utilized in the phase 0 studies, at a tertiary referral
      center. INTERVENTION: IDEAL model implementation in the development of RKT with
      regional hypothermia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For phase 0
      studies, the outcomes evaluated included pelvic and body temperature
      measurements, and technical feasibility assessment. The primary outcome during
      phase 1 was post-transplant graft function. Other outcomes measured were
      operative and ischemic times, perioperative complications, and intracorporeal
      graft surface temperature. RESULTS AND LIMITATIONS: Phase 0 (simulation phase):
      Pelvic cooling to 15-20(o)C was achieved reproducibly. Using the surgical
      approach developed for robotic radical prostatectomy, vascular and ureterovesical
      anastomoses could be done without redocking the robot. Phase 1 (innovation
      phase): All patients underwent live-donor RKT in the lithotomy position. All
      grafts functioned immediately. Mean console, anastomotic, and warm ischemia times
      were 154 min, 29 min, and 2 min, respectively. One patient was re-explored on
      postoperative day 1. CONCLUSIONS: Adherence to the IDEAL guidelines put forth by
      the Balliol Collaboration provided a practical framework for the establishment of
      a novel surgical procedure, RKT with regional hypothermia, without exposing the
      initial patients to unacceptable risk. PATIENT SUMMARY: The IDEAL model allows
      safe introduction of new surgical techniques without compromising patient
      outcomes.

PMID- 24287317
TI  - Reply from authors re: Arthur L. Burnett. Erection rehabilitation after radical
      prostatectomy: definite purpose, indefinite strategy. Eur Urol 2014;65:597-8:
      although erection rehabilitation after prostatectomy remains indefinite, the most
      effective treatment, the earliest recovery, and the preservation of erectile
      function remain a definite goal.

PMID- 24287318
TI  - Do erectile dysfunction and cardiovascular disease have the same mechanism?

PMID- 24287319
TI  - Superior quality of life and improved surgical margins are achievable with
      robotic radical prostatectomy after a long learning curve: a prospective single
      surgeon study of 1552 consecutive cases.
AB  - BACKGROUND: Comparative studies suggest functional and perioperative superiority
      of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy
      (ORP). OBJECTIVE: To determine whether high-volume experienced open surgeons can
      improve their functional and oncologic outcomes with RARP and, if so, how many
      cases are required to surpass ORP outcomes and reach the learning curve plateau.
      DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study compared two
      surgical techniques: 1552 consecutive men underwent RARP (866) or ORP (686) at a
      single Australian hospital from 2006 to 2012, by one surgeon with 3000 prior
      ORPs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic and
      clinicopathologic data were collected prospectively. The Expanded Prostate Cancer
      Index Composite quality of life (QoL) questionnaire was administered at baseline,
      1.5, 3, 6, 12, and 24 mo. Multivariate linear and logistic regression modelled
      the difference in QoL domains and positive surgical margin (PSM) odds ratio (OR),
      respectively, against case number. RESULTS AND LIMITATIONS: A total of 1511 men
      were included in the PSM and 609 in the QoL analysis. RARP sexual function scores
      surpassed ORP scores after 99 RARPs and increased to a mean difference at 861st
      case of 11.0 points (95% confidence interval [CI], 5.9-16.1), plateauing around
      600-700 RARPs. Early urinary incontinence scores for RARP surpassed ORP after 182
      RARPs and increased to a mean difference of 8.4 points (95% CI, 2.1-14.7),
      plateauing around 700-800 RARPs. The odds of a pT2 PSM were initially higher for
      RARP but became lower after 108 RARPs and were 55% lower (OR: 0.45; 95% CI, 0.22
      0.92) by the 866th RARP. The odds of a pT3/4 PSM were initially higher for RARP
      but decreased, plateauing around 200-300 RARPs with an OR of 1.15 (0.68-1.95) at
      the 866th RARP. Limitations include single-surgeon data and residual confounding.
      CONCLUSIONS: RARP had a long learning curve with inferior outcomes initially, and
      then showed progressively superior sexual, early urinary, and pT2 PSM outcomes
      and similar pT3 PSM and late urinary outcomes. Learning RARP was worthwhile for
      this high-volume surgeon, but the learning curve may not be justifiable for late
      career/low-volume surgeons; further studies are needed.

PMID- 24287320
TI  - Chronic kidney disease in older people with intellectual disability: results of
      the HA-ID study.
AB  - With increasing longevity and cardiovascular events, chronic kidney disease may
      also become a significant problem in older people with intellectual disability
      (ID). We studied prevalence and associations of chronic kidney disease as part of
      the Healthy Ageing and Intellectual Disability (HA-ID) study, a large Dutch cross
      sectional study among people with ID aged 50 years and over, using creatinine and
      cystatin-C measurement in plasma. Glomerular filtration rate (GFR) was calculated
      using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equations. Equations based on creatinine (as
      the MDRD equation) may underestimate kidney dysfunction in people with
      sarcopenia, because low muscle mass leads to a low creatinine production.
      Therefore, also prevalence of chronic kidney disease was studied in the
      sarcopenic group, using different GFR equations. Prevalence of chronic kidney
      disease, among 635 participants, was 15.3%, which equals prevalence in the
      general Dutch population. In the group of participants with sarcopenia (n=82),
      the CKD-EPI equation based on creatinine and cystatin-C gave a higher prevalence
      of chronic kidney disease than did the MDRD equation, but confidence intervals
      were very wide. Chronic kidney disease was associated with higher age, Down
      syndrome, obesity, hypercholesterolemia and hypothyroid disease. GFR should be
      measured in all older people with ID and polypharmacy, and in older people with
      ID and Down syndrome as part of the regular health checks. Moreover, if
      sarcopenia is present and information on GFR is required, this should not be
      measured based on creatinine only, but additional measures, such as cystatin-C,
      should be taken into account. 

PMID- 24287321
TI  - "To serve and protect": enzyme inhibitors as radiopeptide escorts promote tumor
      targeting.
AB  - Radiolabeled octreotide analogs are most successfully being applied today in
      clinical cancer imaging and treatment. Propagation of this paradigm to other
      radiopeptide families has been greatly hampered by the inherent poor metabolic
      stability of systemically administered peptide analogs. We hypothesized that the
      in vivo coadministration of specific enzyme inhibitors would improve peptide
      bioavailability and hence tumor uptake. Through single coinjection of the neutral
      endopeptidase inhibitor phosphoramidon (PA), we were able to provoke remarkable
      rises in the percentages of circulating intact somatostatin, gastrin, and
      bombesin radiopeptides in mouse models, resulting in a remarkable increase in
      uptake in tumor xenografts in mice. METHODS: The peptide conjugates [DOTA
      Ala(1)]SS14 (DOTA-Ala-Gly-c[Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys]-OH),
      PanSB1 (DOTA-PEG2-dTyr-Gln-Trp-Ala-Val-betaAla-His-Phe-Nle-NH2), and DOTA-MG11
      (DOTA-dGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) were labeled with (111)In by 20 min
      of heating at an acidic pH. Metabolic stability was studied with high-performance
      liquid chromatography analysis of blood samples collected 5 min after the
      injection of the test radiopeptide alone or with PA into mice. Biodistribution
      was studied after injection of each (111)In-labeled radiopeptide alone or after
      coinjection of PA in tumor-bearing severe combined immunodeficient (SCID) mice.
      RESULTS: The amount of intact [(111)In-DOTA-Ala(1)]SS14 detected in the mouse
      circulation at 5 min after the injection of PA increased impressively-from less
      than 2% to 86%-whereas the uptake in AR4-2J xenografts rose from less than 1
      percentage injected dose per gram of tissue (%ID/g) to 14 %ID/g at 4 h after
      injection. Likewise, the coadministration of PA resulted in a marked increase in
      the amount of circulating intact (111)In-PanSB1-from 12% to 80%-at 5 min after
      injection, and radioligand uptake in human PC-3 xenografts in SCID mice escalated
      from less than 4 %ID/g to greater than 21 %ID/g at 4 h after injection. In a
      similar manner, the coadministration of PA resulted in an equally impressive
      increase in intact [(111)In-DOTA]MG11 levels in the mouse bloodstream-from less
      than 5% to 70%-at 5 min after injection, leading to a remarkable increase in
      radiotracer uptake-from 2 %ID/g to greater than 15 %ID/g-in both AR4-2J tumors
      and A431(CCKR+) tumors (i.e., tumors induced by A431 cells transfected to stably
      express the human cholecystokinin subtype 2 receptor) in mice at 4 h after
      injection. This effect was well visualized by SPECT/CT imaging of AR4-2J tumor
      bearing mice at 4 h after injection. CONCLUSION: The results of this study
      clearly demonstrate that the coadministration of key enzyme inhibitors can
      effectively prolong the survival of radiolabeled peptides in the circulation,
      securing their safe transit to the target. This strategy clearly provoked an
      unprecedented increase in radiolabel accumulation in tumor xenografts in mice;
      this increase might translate into higher diagnostic sensitivity or improved
      therapeutic efficacy of radiopeptide drugs in cancer patients. Hence, our
      findings provide exciting new opportunities for the application of biodegradable
      (radio)peptide drugs of either natural or synthetic origin as well as for the
      rationale design of analogs that are stable in vivo.

PMID- 24287323
TI  - Study of consensus-based time synchronization in wireless sensor networks.
AB  - Recently, various consensus-based protocols have been developed for time
      synchronization in wireless sensor networks. However, due to the uncertainties
      lying in both the hardware fabrication and network communication processes, it is
      not clear how most of the protocols will perform in real implementations. In
      order to reduce such gap, this paper investigates whether and how the typical
      consensus-based time synchronization protocols can tolerate the uncertainties in
      practical sensor networks through extensive testbed experiments. For two typical
      protocols, i.e., Average Time Synchronization (ATS) and Maximum Time
      Synchronization (MTS), we first analyze how the time synchronization accuracy
      will be affected by various uncertainties in the system. Then, we implement both
      protocols on our sensor network testbed consisted of Micaz nodes, and investigate
      the time synchronization performance and robustness under various network
      settings. Noticing that the synchronized clocks under MTS may be slightly faster
      than the desirable clock, by adopting both maximum consensus and minimum
      consensus, we propose a modified protocol, MMTS, which is able to drive the
      synchronized clocks closer to the desirable clock while maintaining the
      convergence rate and synchronization accuracy of MTS. 

PMID- 24287322
TI  - In vivo detection of monoaminergic degeneration in early Parkinson disease by
      (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine PET.
AB  - PET with (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-DTBZ), a novel
      radiotracer targeting vesicular monoamine transporter type 2 (VMAT2), has been
      proven as a useful imaging marker to measure dopaminergic integrity. METHODS: The
      aim of this study was to evaluate the capability of (18)F-DTBZ PET in detecting
      the monoaminergic degeneration in early Parkinson disease (PD) in vivo. Seventeen
      age-matched healthy subjects and 30 PD patients at early stage of disease
      (duration of disease <= 5 y) with mild and unilateral motor symptoms underwent
      (18)F-DTBZ PET scans. The severity of disease, including Unified Parkinson
      Disease Rating Scale and modified Hoehn and Yahr Stage (mHY), were recorded at
      off-medication states. The standardized volumes of interest were applied to the
      spatial normalized image for quantification analysis. The specific uptake ratios
      (SURs) were calculated according to the formula (specific volumes-of-interest
      counts/occipital cortex counts) - 1. SUR measurements were summarized for each
      brain region. RESULTS: The mean duration of disease in the PD group was 3.2 +/-
      2.1 y (range, 0.5-5 y). The mean mHY was 1.0 +/- 0.1 (range, 1-1.5). The SURs of
      bilateral caudate, anterior putamen, posterior putamen, substantia nigra, and
      nucleus accumbens were significantly lower in PD patients than those of healthy
      subjects. The reduction of SURs was most severe in the contralateral (the brain
      regions that are located opposite to the symptomatic side) posterior putamen (
      81%), followed by the ipsilateral posterior putamen (-67%). Receiver-operating
      characteristic curve analysis showed that the SURs of the bilateral posterior
      putamen and contralateral anterior putamen had a sensitivity of 100% and
      specificity of 100% in differentiating PD patients from healthy subjects.
      CONCLUSION: (18)F-DTBZ PET was as an excellent tool for the early diagnosis of
      PD. The obvious decline of (18)F-DTBZ uptake in the ipsilateral (asymptomatic)
      striatum suggested that (18)F-DTBZ PET might serve as an in vivo biomarker to
      detect the monoaminergic degeneration in the premotor phase of PD.

PMID- 24287324
TI  - [Breast cancer risk associated with night work].

PMID- 24287325
TI  - Elemental and chemical characterization of dolphin enamel and dentine using X-ray
      and Raman microanalyzes (Cetacea: Delphinoidea and Inioidea).
AB  - Dolphins show increased tooth number and simplified tooth shape compared to most
      mammals, together with a simpler ultrastructural organization and less demanding
      biomechanical function. However, it is unknown if these factors are also
      reflected in the chemical composition of their teeth. Here, the bulk chemical
      composition and elemental distribution in enamel and dentine of extant dolphins
      were characterized and interpreted using X-ray and spectroscopy techniques. Teeth
      of 10 species of Delphinida were analyzed by WDX, EDX and Raman spectroscopy. For
      most of the species sampled, the mineral content was higher in enamel than in
      dentine, increasing from inner towards outer enamel. The transition from dentine
      to enamel was marked by an increase in concentration of the major components Ca
      and P, but also in Na and Cl. Mg decreased from dentine to enamel. Concentrations
      of Sr and F were often low and below detection limits, but F peaked at the outer
      enamel region for some species. Raman spectroscopy analyzes showed
      characteristics similar to carbonated hydroxyapatite, with the strongest peak for
      the phosphate PO4(3-) stretching mode at 960-961cm(-1). Dentine samples revealed
      a higher diversity of peaks representative of organic components and proteins
      than enamel. The similar distribution pattern and small variation in average
      concentration of major and minor elements in dentine and enamel of dolphins
      suggest that they are subject to strong physiological control. A clear trend of
      the elemental variations for all dolphin species sampled suggests that the
      general pattern of tooth chemistry is conserved among the Mammalia. 

PMID- 24287326
TI  - RON (recepteur d'origine nantais) expression and its association with tumor
      progression in laryngeal squamous cell carcinoma.
AB  - OBJECTIVES: Several human tumor tissues show an aberrant expression and
      activation of recepteur d'origine nantais (RON). In this paper, we investigate
      the expression of RON in human laryngeal squamous cell carcinoma (SCC) and
      evaluate whether RON affects the tumor cell progression in human laryngeal SCC
      cell line. METHODS: Immunohistochemistry was used to assess RON expression in
      human laryngeal SCC. To evaluate the impact of RON knockdown, the cell invasion
      assay and cell migration assay using small-interfering RNA were performed.
      RESULTS: The expression of RON protein was dominantly observed in laryngeal SCC
      tissues relative to adjacent normal mucosa in all cases. Knockdown of RON
      resulted in significantly reduced cell invasion in human laryngeal SCC cells.
      Cell migration showed a marked decrease in RON knockdown laryngeal SCC cells
      compared to the negative control laryngeal SCC cells. Laryngeal SCC cell
      migration was enhanced by incubation with macrophage stimulating protein (MSP).
      CONCLUSION: RON is highly expressed in human laryngeal SCC. We suggest that RON
      plays an important role in invasion, and metastasis of laryngeal SCC.

PMID- 24287327
TI  - Bispectral index (BIS) and suppression ratio (SR) as an early predictor of
      unfavourable neurological outcome after cardiac arrest.
AB  - INTRODUCTION: Predicting the neurological outcome after cardiopulmonary
      resuscitation (CPR) is extremely difficult. We tested the hypothesis whether
      monitoring of bispectral index (BIS) and suppression ratio (SR) could serve as an
      early prognostic indicator of neurological outcomes after CPR. METHODS: Cerebral
      monitoring (BIS, SR) was started as soon as possible after initiation of CPR and
      was continued for up to 72h. The functional neurological outcome was measured on
      day 3, day 7 and again one month after CPR via a clinical examination and
      assessment according to the cerebral performance category score (CPC). RESULTS:
      In total 79 patients were included. Of these, 26 patients (32.9%) survived the
      observation period of one month; 7 of them (8.9%) showed an unfavourable
      neurological outcome. These 7 patients had significantly lower median BIS values
      (25 [21;37] vs. 61 [51;70]) and higher SR (56 [44;64] vs. 7 [1;22]) during the
      first 4h after the initiation of CPR. Using BIS<40 as threshold criteria,
      unfavourable neurological outcome was predicted with a specificity of 89.5% and a
      sensitivity of 85.7%. The odds ratio for predicting an unfavourable neurological
      outcome was 0.921 (95% CI 0.853-0.985). The likelihood to remain in a poor
      neurological condition decreased by 7.9% for each additional point of BIS, on
      average. CONCLUSION: Our results suggest that BIS and SR are helpful tools in the
      evaluation of the neurological outcomes of resuscitated patients. Nevertheless,
      therapeutic decisions have to be confirmed through further examinations due to
      the far-ranging consequences of false positive results.

PMID- 24287328
TI  - Requirement for a structured algorithm in cardiac arrest following major trauma:
      epidemiology, management errors, and preventability of traumatic deaths in
      Berlin.
AB  - BACKGROUND: Despite continuous innovation in trauma care, fatal trauma remains a
      significant medical and socioeconomic problem. Traumatic cardiac arrest (tCA) is
      still considered a hopeless situation, whereas management errors and
      preventability of death are neglected. We analyzed clinical and autopsy data from
      tCA patients in an emergency-physician-based rescue system in order to reveal
      epidemiologic data and current problems in the successful treatment of tCA.
      MATERIAL AND METHODS: Epidemiological and autopsy data of all unsuccessful tCPR
      cases in a one-year-period in Berlin, Germany (n=101, Group I) and clinical data
      of all cases of tCPR in a level 1 trauma centre in an 6-year period (n=52, Group
      II) were evaluated. Preventability of traumatic deaths in autopsy cases (n=22)
      and trauma-management failures were prospectively assessed. RESULTS: In 2010, 23%
      of all traumatic deaths in Berlin received tCPR. Death after tCPR occurred
      predominantly prehospital (PH;74%) and only 26% of these patients were
      hospitalized. Of 52 patients (Group II), 46% required tCPR already PH and 81% in
      the emergency department (ED). In 79% ROSC was established PH and 53% in the ED.
      The survival rate after tCPR was 29% with 27% good neurological outcome.
      Management errors occurred in 73% PH; 4 cases were judged as potentially or
      definitive preventable death. CONCLUSION: Trauma CPR is beyond routine with the
      need for a tCPR-algorithm, including chest/pericardial decompression, external
      pelvic stabilization and external bleeding control. The prehospital trauma
      management has the highest potential to improve tCPR and survival. Therefore, we
      suggested a pilot prehospital tCPR-algorithm.

PMID- 24287329
TI  - Outcomes of delivery room CPR among very premature neonates: what are the
      challenges we face in the setting of regionalized perinatal care?

PMID- 24287330
TI  - Intubating laryngeal mask airway placement by non-physician healthcare providers
      in management out-of-hospital cardiac arrests: a case series.
AB  - AIM OF THE STUDY: The role of supralaryngeal devices in airway management in out
      of-hospital cardiac arrests (OHCA) remains controversial. The aim of this
      prospective observational trial was to evaluate the feasibility and effectiveness
      of intubating laryngeal mask airway (ILMA) when used by trained prehospital
      emergency nurses in the setting of OHCA. METHODS: After approval from the
      Research Ethics Board, prehospital emergency nurses trained in placement of ILMA
      (FastrachTM, LMA Vitaid, Toronto, Ontario, Canada) followed a formal protocol for
      airway control during OHCA. The primary outcome was the success rate of ILMA
      placement, while secondary outcomes were success rate of tracheal intubation
      through the ILMA, and the incidence of regurgitation of gastric contents.
      RESULTS: During the study period, 302 ILMA placements were attempted by emergency
      nurses during OHCA resuscitation. After ILMA placement, but before attempt for
      intubation, ventilation was possible in 290 patients (96%). Obstruction or major
      leaks were observed in 12 patients (4%). Tracheal tube insertion through the ILMA
      was attempted in 265 patients, and was performed in 254 (95.8%). This allowed for
      proper lung ventilation through the tracheal tube in 242 cases whereas 12 tubes
      were esophageal or proved obstructed. Regurgitation of gastric contents occurred
      in 43 (14.2%) patients; in 23 cases before arrival of the first aid team, in 18
      cases before ILMA placement, and in 2 cases after the ILMA placement. CONCLUSION:
      The use of ILMA for airway management by trained emergency nurses during OHCA
      resuscitation is feasible and allows for effective airway management. The success
      rate of tracheal tube placement through the ILMA was high. In addition, the
      incidence of regurgitation was lower when using the ILMA than that previous
      historical reports with face-mask ventilation.

PMID- 24287331
TI  - The epidemiology of respiratory arrests in a teaching hospital.
AB  - AIMS: We aimed to characterise antecedent causes and outcomes of respiratory
      arrests occurring within a metropolitan tertiary teaching hospital in Melbourne,
      Australia. METHODS: We conducted a retrospective audit of respiratory arrests
      within our hospital over a 6-year period. Data were collected regarding patient
      characteristics, preceding clinical state, presumed causes and outcomes of
      arrests. We also compared outcomes of respiratory arrests to that of cardiac
      arrests occurring over the same period. RESULTS: We identified 82 respiratory
      arrests, occurring at a rate of 0.57/1000 inpatient admissions. Pre-existing
      respiratory, neurologic and cardiac disease was common, as was multi-morbidity.
      Preceding clinical instability was evident in 39% of arrests, most commonly
      elevated respiratory rate or progressive hypoxia. Pulmonary oedema was the most
      common cause of respiratory arrest followed by aspiration, neurologic events,
      medication side-effects, and tracheostomy-tube complications. In-hospital
      mortality for respiratory arrests was 25.1%, compared with 74.9% for cardiac
      arrests (p<0.001) over the same time period. CONCLUSIONS: Although rare,
      respiratory arrests are associated with significantly lower in-hospital mortality
      than cardiac arrests. Further studies are needed to better predict respiratory
      arrests and identify interventions to reduce incidence and improve outcomes.

PMID- 24287332
TI  - Network analysis of GWAS data.
AB  - Genome-wide association studies (GWAS) identify genetic variants that distinguish
      a control population from a population with a specific trait. Two challenges in
      GWAS are: (1) identification of the causal variant within a longer haplotype that
      is associated with the trait; (2) identification of causal variants for polygenic
      traits that are caused by variants in multiple genes within a pathway. We review
      recent methods that use information in protein-protein and protein-DNA
      interaction networks to address these two challenges. 

PMID- 24287333
TI  - Using chromatin marks to interpret and localize genetic associations to complex
      human traits and diseases.
AB  - While studies to associate genomic variants to complex traits have gradually
      become increasingly productive, the molecular mechanisms that underlie these
      associations are rarely understood. Because only a small fraction of trait
      associated variants can be linked to coding sequences, investigators have
      speculated that many of the underlying causal alleles influence non-coding gene
      regulatory sites. Recent studies have successfully identified examples of
      mechanisms for non-coding alleles at individual loci. Now, genome-wide chromatin
      assays have resulted in maps of dozens of genomic annotations of the non-coding
      genome across multiple different tissues, cell types and cell lines. This gives a
      tremendous opportunity to integrate these annotations with complex trait signals
      to globally interpret associated variants, and prioritize likely causal alleles.
      Here, we review the examples of mechanisms by which non-coding, common alleles
      result in phenotypes. We discuss the efforts to integrate common trait-associated
      variants with genomic annotations. Finally, we highlight some caveats of these
      approaches and outline future directions for improvement. 

PMID- 24287334
TI  - Genetic architecture of quantitative traits and complex diseases.
AB  - More than 150 years after Mendel discovered the laws of heredity, the genetic
      architecture of phenotypic variation remains elusive. Here, we discuss recent
      progress in deciphering how genotypes map onto phenotypes, sources of genetic
      complexity, and how model organisms are illuminating general principles about the
      relationship between genetic and phenotypic variation. Moreover, we highlight
      insights gleaned from large-scale sequencing studies in humans, and how this
      knowledge informs outstanding questions about the genetic architecture of
      quantitative traits and complex diseases. Finally, we articulate how the
      confluence of technologies enabling whole-genome sequencing, comprehensive
      phenotyping, and high-throughput functional assays of polymorphisms will
      facilitate a more principled and mechanistic understanding of the genetic
      architecture of phenotypic variation. 

PMID- 24287336
TI  - Direct Kernel Perceptron (DKP): ultra-fast kernel ELM-based classification with
      non-iterative closed-form weight calculation.
AB  - The Direct Kernel Perceptron (DKP) (Fernandez-Delgado et al., 2010) is a very
      simple and fast kernel-based classifier, related to the Support Vector Machine
      (SVM) and to the Extreme Learning Machine (ELM) (Huang, Wang, & Lan, 2011), whose
      alpha-coefficients are calculated directly, without any iterative training, using
      an analytical closed-form expression which involves only the training patterns.
      The DKP, which is inspired by the Direct Parallel Perceptron, (Auer et al.,
      2008), uses a Gaussian kernel and a linear classifier (perceptron). The weight
      vector of this classifier in the feature space minimizes an error measure which
      combines the training error and the hyperplane margin, without any tunable
      regularization parameter. This weight vector can be translated, using a variable
      change, to the alpha-coefficients, and both are determined without iterative
      calculations. We calculate solutions using several error functions, achieving the
      best trade-off between accuracy and efficiency with the linear function. These
      solutions for the alpha coefficients can be considered alternatives to the ELM
      with a new physical meaning in terms of error and margin: in fact, the linear and
      quadratic DKP are special cases of the two-class ELM when the regularization
      parameter C takes the values C=0 and C=infinity. The linear DKP is extremely
      efficient and much faster (over a vast collection of 42 benchmark and real-life
      data sets) than 12 very popular and accurate classifiers including SVM, Multi
      Layer Perceptron, Adaboost, Random Forest and Bagging of RPART decision trees,
      Linear Discriminant Analysis, K-Nearest Neighbors, ELM, Probabilistic Neural
      Networks, Radial Basis Function neural networks and Generalized ART. Besides,
      despite its simplicity and extreme efficiency, DKP achieves higher accuracies
      than 7 out of 12 classifiers, exhibiting small differences with respect to the
      best ones (SVM, ELM, Adaboost and Random Forest), which are much slower. Thus,
      the DKP provides an easy and fast way to achieve classification accuracies which
      are not too far from the best one for a given problem. The C and Matlab code of
      DKP are freely available.

PMID- 24287337
TI  - Influence of sodium content on the properties of bioactive glasses for use in air
      abrasion.
AB  - Air abrasion is used in minimally invasive dentistry for preparing cavities,
      while removing no or little sound dentine or enamel, and the use of bioactive
      glass (rather than alumina) as an abrasive could aid in tooth remineralization.
      Melt-derived bioactive glasses (SiO2-P2O5-CaO-CaF2-Na2O) with low sodium content
      (0 to 10 mol% Na2O in exchange for CaO) for increased hardness, high phosphate
      content for high bioactivity and fluoride content for release of fluoride and
      formation of fluorapatite were produced, and particles between 38 and 80 um in
      size were used for cutting soda-lime silicate glass microscope slides and human
      enamel. Vickers hardness increased with decreasing Na2O content, owing to a more
      compact silicate network in low sodium content glasses, resulting in shorter
      cutting times. Cutting times using bioactive glass were significantly longer than
      using the alumina control (29 um) when tested on microscope slides; however,
      glasses showed more comparable results when cutting human enamel. The bioactive
      glasses formed apatite in Tris buffer within 6 h, which was significantly faster
      than Bioglass(r) 45S5 (24 h), suggesting that the hardness of the glasses makes
      them suitable for air abrasion application, while their high bioactivity and
      fluoride content make them of interest for tooth remineralization. 

PMID- 24287335
TI  - Edgotype: a fundamental link between genotype and phenotype.
AB  - Classical 'one-gene/one-disease' models cannot fully reconcile with the
      increasingly appreciated prevalence of complicated genotype-to-phenotype
      associations in human disease. Genes and gene products function not in isolation
      but as components of intricate networks of macromolecules (DNA, RNA, or proteins)
      and metabolites linked through biochemical or physical interactions, represented
      in 'interactome' network models as 'nodes' and 'edges', respectively.
      Accordingly, mechanistic understanding of human disease will require
      understanding of how disease-causing mutations affect systems or interactome
      properties. The study of 'edgetics' uncovers specific loss or gain of
      interactions (edges) to interpret genotype-to-phenotype relationships. We review
      how distinct genetic variants, the genotype, lead to distinct phenotypic
      outcomes, the phenotype, through edgetic perturbations in interactome networks
      altogether representing the 'edgotype'. 

PMID- 24287338
TI  - Laparoscopic assessment in surgical trauma (LAST): a "last" diagnostic step in
      the trauma bay.

PMID- 24287339
TI  - Regulation of a putative corticosteroid, 17,21-dihydroxypregn-4-ene,3,20-one, in
      sea lamprey, Petromyzon marinus.
AB  - In higher vertebrates, in response to stress, the hypothalamus produces
      corticotropin-releasing hormone (CRH), which stimulates cells in the anterior
      pituitary to produce adrenocorticotropic hormone (ACTH), which in turn stimulates
      production of either cortisol (F) or corticosterone (B) by the adrenal tissues.
      In lampreys, however, neither of these steroids is present. Instead, it has been
      proposed that the stress steroid is actually 17,21-dihydroxypregn-4-ene-3,20
      dione (11-deoxycortisol; S). However, there have been no studies yet to determine
      its mechanism of regulation or site of production. Here we demonstrate that (1)
      intraperitoneal injections of lamprey-CRH increase plasma S in a dose dependent
      manner, (2) intraperitoneal injections of four lamprey-specific ACTH peptides at
      100MUg/kg, did not induce changes in plasma S concentrations in either males or
      females; (3) two lamprey-specific gonadotropin-releasing hormones (GnRH I and
      III) and arginine-vasotocin (AVT), all at single doses, stimulated S production
      as well as, or to an even greater extent than CRH; (4) sea lamprey mesonephric
      kidneys, in vitro, converted tritiated 17alpha-hydroxyprogesterone (17alpha-P)
      into a steroid that had the same chromatographic properties (on HPLC and TLC) as
      S; (5) kidney tissues released significantly more immunoassayable S into the
      incubation medium than gill, liver or gonad tissues. One interpretation of these
      results is that the corticosteroid production of the sea lamprey, one of the
      oldest extant vertebrates, is regulated through multiple pathways rather than the
      classical HPI-axis. However, the responsiveness of this steroid to the GnRH
      peptides means that a reproductive rather than a stress role for this steroid
      cannot yet be ruled out. 

PMID- 24287340
TI  - Peripheral injections of cholecystokinin, apelin, ghrelin and orexin in cavefish
      (Astyanax fasciatus mexicanus): effects on feeding and on the brain expression
      levels of tyrosine hydroxylase, mechanistic target of rapamycin and appetite
      related hormones.
AB  - The effects of intraperitoneal injections of cholecystokinin (CCK), apelin,
      ghrelin, and orexin on food intake were examined in the blind cavefish Astyanax
      fasciatus mexicanus. CCK (50ng/g) induced a decrease in food intake whereas
      apelin (100ng/g), orexin (100ng/g), and ghrelin (100ng/g) induced an increase in
      food intake as compared to saline-injected control fish. In order to better
      understand the central mechanism by which these hormones act, we examined the
      effects of injections on the brain mRNA expression of two metabolic enzymes,
      tyrosine hydroxylase (TH), and mechanistic target of rapamycin (mTOR), and of
      appetite-regulating peptides, CCK, orexin, apelin and cocaine and amphetamine
      regulated transcript (CART). CCK injections induced a decrease in brain apelin
      injections, apelin injections induced an increase in TH, mTOR, and orexin brain
      expressions, orexin treatment increased brain TH expression and ghrelin
      injections induced an increase in mTOR and orexin brain expressions. CART
      expression was not affected by any of the injection treatments. Our results
      suggest that the enzymes TH and mTOR and the hormones CCK, apelin, orexin, and
      ghrelin all regulate food intake in cavefish through a complex network of
      interactions. 

PMID- 24287341
TI  - 17beta-Estradiol induces supernumerary primordial germ cells in embryos of the
      polychaete Platynereis dumerilii.
AB  - In the polychaete Platynereis dumerilii exactly four primordial germ cells (PGCs)
      arise in early development and are subject to a transient mitotic arrest until
      the animals enter gametogenesis. In order to unravel the mechanisms controlling
      the number of PGCs in Platynereis, we tested whether the steroid 17beta-estradiol
      (E2) is able to induce PGC proliferation, as it had been described in other
      species. Our data provide strong support for such a mechanism, showing that E2
      significantly increases the occurrence of larvae with supernumerary PGCs in
      Platynereis in a dose dependent manner. E2 responsiveness is restricted to early
      developmental stages, when the PGCs are specified. During these stages, embryos
      exhibit high expression levels of the estradiol receptor (ER). The ER transcript
      localizes to the yolk-free cytoplasm of unfertilized eggs and segregates into the
      micromeres during cleavage stages. Nuclear ER protein is found asymmetrically
      distributed between daughter cells. Neither transcript nor protein is detectable
      in PGCs at larval stages. Addition of the specific estradiol receptor inhibitor
      ICI-182,780 (ICI) abolishes the proliferative effect of E2, suggesting that it is
      mediated by ER signaling. Our study reports for the first time an ER mediated
      proliferative effect of E2 on PGCs in an invertebrate organism. 

PMID- 24287342
TI  - Non-cephalosporin-susceptible, glucose non-fermentative Gram-negative bacilli
      meningitis in post-neurosurgical adults: clinical characteristics and therapeutic
      outcome.
AB  - OBJECTIVE: The clinical and laboratory characteristics of non-cephalosporin
      susceptible (non-CS) glucose non-fermentative Gram-negative (G(-)) infections in
      adults with postneurosurgical meningitis are rarely examined solely in the
      literature. METHODS: The data of 28 post-neurosurgical adults meningitis with
      glucose non-fermentative G(-) infections, collected during a study period of 5
      years (2006-2010), were reviewed. The clinical and laboratory data between the
      non-cephalosporin-susceptible groups and the cephalosporin-susceptible groups
      were compared. RESULTS: A total of 30 G(-) strains were collected from the 28
      enrolled cases. Among the implicated glucose non-fermentative G(-) strains, 18
      strains, belonging to 17 cases, were non-CS. Among the 18 non-cephalosporin
      susceptible strains, Acinetobacter spp. (39%, 7/18) was the most common, followed
      by Pseudomonas spp. (22%, 4/18), Stenotrophomonas maltophilia (22%, 4/18) and
      Elizabethkingia meningoseptica (11%, 2/18). With a comparative analysis, there
      were no significant difference between the non-cephalosporin-susceptible and
      cephalosporin-susceptible glucose non-fermentative G(-) groups. The clinical and
      laboratory data were also of no statistical significance between the fatal (n=4)
      and non-fatal (n=13) non-cephalosporin-susceptible groups. CONCLUSION: Sixty
      percent (18/30) of implicated glucose non-fermentative G(-) strains of post-NS
      meningitis in adults are non-cephalosporin-susceptible. Among the non
      cephalosporin-susceptible glucose non-fermentative G(-) strains, Acinetobacter
      spp., Pseudomonas spp., S. maltophilia and E. meningoseptica are the commonly
      implicated pathogens, and their emergence in this specific group of meningitis
      has caused a therapeutic dilemma. The clinical manifestations of non
      cephalosporin-susceptible glucose non-fermentative G(-) meningitis were not
      unique; therefore, only bacterial culture and antimicrobial susceptibility test
      are the methods for identification confirmation.

PMID- 24287343
TI  - Advances in transplantation 1940-2014.
AB  - The history of medicine is that what was inconceivable yesterday and barely
      achievable today often becomes routine tomorrow. Liver transplantation began with
      almost no resources at the same time as the tentative first steps were taken to
      land a man on the moon. Because human lives would be at stake, both objectives
      had a sacramental element from the outset: a solemnly binding commitment to
      perfection. The gift of an organ is really a gift of life, and something as
      valuable as a life-saving organ is more important to a suffering patient than
      wealth or power. The concept of a team approach to the care of the transplant
      patient is an important factor in the development of a successful program. This
      has resulted in recipient survival rates reaching 90% at one year. 

PMID- 24287344
TI  - Infrastructure, logistics and regulation of transplantation: UNOS.
AB  - Organ transplantation has evolved into the standard of care for patients with end
      stage organ failure. Despite considering increasingly complex transplant
      recipients for organs recovered from donors with increasing comorbid conditions,
      1-year patient survival following kidney transplantation is 97% in the United
      States, whereas liver transplant recipient 1-year survival is 90%. There were
      16,485 kidney recipients in the United States in 2012, and 6256 patients who
      underwent liver transplantation. The intent of this review is to highlight the
      logistics required for transplantation as well as reviewing the current oversight
      of transplantation. 

PMID- 24287345
TI  - Allocation of resources for organ transplantation.
AB  - Over the last 6 decades, organ transplantation has achieved great success to
      become standard therapy for the treatment of patients with end-stage organ
      failure. With this success has emerged candidate wait lists that greatly
      outnumber the current supply of deceased donor organs. The increasing number of
      candidates and transplants performed has resulted in an organ allocation process
      that occurs at a local, regional, and sometimes national level. A brief
      description of the history is presented as well as the methodologies involved in
      allocation of a donor organ to a single recipient. 

PMID- 24287346
TI  - Ethical and legal issues related to the donation and use of nonstandard organs
      for transplants.
AB  - Transplantation of nonstandard or expanded criteria donor organs creates several
      potential ethical and legal problems in terms of consent and liability, and new
      challenges for research and service development; it highlights the need for a
      system of organ donation that responds to an evolving ethical landscape and
      incorporates scientific innovation to meet the needs of recipients, but which
      also safeguards the interests and autonomy of the donor. In this article, the use
      of deceased donor organs for transplants that fail to meet standard donor
      criteria and the legitimacy of interventions and research aimed at optimizing
      their successful donation are discussed. 

PMID- 24287347
TI  - Patient selection and preoperative evaluation for transplant surgery.
AB  - Candidates for abdominal transplant undergo a pretransplant evaluation to
      identify associated conditions that may require intervention or that may
      influence a patient's candidacy for transplant. Coronary artery disease is
      prevalent in candidates for abdominal organ transplantation. The optimal approach
      to identify and manage coronary artery disease in the peri-transplant period is
      currently unclear. In liver transplant candidates portopulmonary hypertension and
      hepatopulmonary syndrome should be screened for. Identification of the patient
      who is too sick to benefit from transplant is problematic; with no good evidence
      available decisions should be individualized and made after multidisciplinary
      discussion. 

PMID- 24287348
TI  - Intraoperative care of the transplant patient.
AB  - Patients undergoing abdominal organ transplantation have extensive comorbidities
      that can affect many organ systems including the cardiovascular system.
      Intraoperative anesthesia care can be very challenging and requires thorough
      understanding of the disease specific physiology as well as knowledge of the
      comorbidities and the surgical procedure. There is no approach to intraoperative
      anesthesia care that will work equally well for every center but standardization
      of protocols for each transplant center will improve patient care and safety and
      ultimately contributes to superior outcomes. In this article we provide
      background and suggestions that will help with the development of standardized
      protocols for intraoperative management. 

PMID- 24287349
TI  - Postoperative care/critical care of the transplant patient.
AB  - Critical care of the general surgical patient requires synthesis of the patient's
      physiology, intraoperative events, and preexisting comorbidities. Evaluating an
      abdominal solid-organ transplant recipient after surgery adds a new dimension to
      clinical decisions because the transplanted allograft has undergone its own
      physiologic challenges and now must adapt to a new environment. This donor
      recipient interaction forms the foundation for assessment of early allograft
      function (EAF). The intensivist must accurately assess and support EAF within the
      context of the recipient's current physiology and preexisting comorbidities.
      Optimizing EAF is essential because allograft failure is a significant predictor
      of recipient morbidity and mortality. 

PMID- 24287350
TI  - Current research on organ donor management.
AB  - A shortage of organs is available for transplantation, with 116,000 patients on
      the Organ Procurement and Transplantation Network/United Network for Organ
      Sharing wait list. Because the demand for organs outweighs the supply,
      considerable care must be taken to maximize the number of organs transplanted per
      donor and optimize the quality of recovered organs. Studies designed to determine
      optimal donor management therapies are limited, and this research has many
      challenges. Although evidenced-based guidelines for managing potential organ
      donors do not exist, research in this area is increasing. This article reviews
      the existing literature and highlights recent trials that can guide management. 

PMID- 24287351
TI  - Transplantation in ACOs.
AB  - The United States exhibits subpar health care outcomes compared with the
      Organisation for Economic Co-operation and Development peer group. An urgent need
      exists to address the excessive cost and unsustainable trajectory of expenditures
      associated with US health care. Health care reform ideas based on the Health
      Maintenance Organization and Patient-Centered Medical Home concepts are a
      promising solution to address health care inefficiencies. Accountable Care
      Organizations seek to simultaneously improve quality of care and reduce
      expenditure. 

PMID- 24287352
TI  - Abdominal transplantation.

PMID- 24287353
TI  - Association of obesity and systemic factors with bone marrow lesions at the knee:
      a systematic review.
AB  - OBJECTIVE: The objective of this study was to systematically review the
      literature to determine whether obesity and systemic factors, including age,
      gender, heritability, dietary factors, smoking, serum and urine biomarkers of
      cartilage or bone metabolism, bone-related factors, and medication, are
      associated with knee bone marrow lesions (BMLs) identified on magnetic resonance
      imaging in asymptomatic pre-osteoarthritis and osteoarthritis populations.
      METHODS: Electronic searches of MEDLINE and EMBASE were performed from January 1,
      1996 to September 30, 2012 using the following keywords: bone marrow lesion(s),
      bone marrow (o)edema, osteoarthritis, and knee. Studies examining obesity and non
      biomechanical factors in relation to the presence, incidence, or change in BMLs
      were included. Two independent reviewers extracted data and assessed
      methodological quality of selected studies. Due to the heterogeneity of the
      studies, we performed a best evidence synthesis. RESULTS: Among 30 studies, 17
      were considered high quality. The study populations were heterogeneous in terms
      of symptoms and radiographic knee osteoarthritis. There was strong evidence for
      an association between serum lipids and BMLs and no association between age and
      BMLs. There was moderate evidence for a relationship between obesity and BMLs.
      There was limited evidence for gender, smoking, C-telopeptide of type I collagen,
      anti-bone-resorptive treatments, licofelone, and chondroitin sulfate. There was a
      paucity of evidence for heritability and conflicting evidence for dietary fatty
      acids. CONCLUSION: There is strong evidence for serum lipids and moderate
      evidence for obesity as risk factors for knee BMLs. Given the role of BMLs in the
      pathogenesis of knee osteoarthritis, identification of modifiable risk factors of
      BMLs and therapeutic interventions targeting BMLs has the potential to reduce the
      burden of knee osteoarthritis.

PMID- 24287354
TI  - Effect of shisha vs. cigarette smoking on endothelial function by brachial artery
      duplex ultrasonography: an observational study.
AB  - OBJECTIVE: In this study, we sought to investigate the effect of shisha smoking
      on endothelial function compared to cigarettes, using brachial artery ultrasound
      (BAUS) imaging in asymptomatic young adults with no other cardiovascular risk
      factors. METHODS: This is an observational case-control study where 30 young
      shisha smokers, 30 cigarette smokers and 10 healthy, non-smokers, age- matched
      subjects between 25-35 years old with no cardiovascular risk factors were
      recruited from all around Egypt. Flow-mediated dilation was assessed using
      brachial artery duplex ultrasonography. RESULTS: FMD% was significantly impaired
      among shisha smokers compared to cigarette smokers and non-smokers cigarettes
      (7.9 +/- 3.8% vs. 12 +/- 3.4% and 21.5 +/- 2.5% respectively p<0.001).
      CONCLUSION: Shisha smoking has a more hazardous effect on brachial artery
      endothelial- dependent flow mediated vasodilation compared to cigarette.

PMID- 24287355
TI  - Obesity is a risk factor for acute mountain sickness: a prospective study in
      Tibet railway construction workers on Tibetan plateau.

PMID- 24287356
TI  - [Problems, nurses face within the intensive care units illustrated by four case
      reports].

PMID- 24287357
TI  - Radiofrequency ablation improving LV function in cardiomyopathy secondary to low
      burden of premature ventricular complexes.

PMID- 24287358
TI  - Bilateral pseudoaneurysm secondary to intraarterial tianeptine abuse.

PMID- 24287359
TI  - Right coronary artery spasm-a complication of cardiac pacemaker implantation.

PMID- 24287360
TI  - Cardiology concern on new H3N2 influenza outbreak.

PMID- 24287361
TI  - Elective percutaneous coronary intervention without on-site cardiac surgery: an
      Iranian survey.

PMID- 24287367
TI  - Toothache uncovered the biatrial masses. Carney syndrome.

PMID- 24287368
TI  - A cardiac cyst presented with subacute anterior myocardial infarction. Hydatid
      cyst.

PMID- 24287369
TI  - TRP-channels as key integrators of lipid pathways in nociceptive neurons.
AB  - TRP-channels are the most prominent family of ligand-gated ion channels for pain
      perception. In sensory neurons, TRPV1-V4, TRPA1 and TRPM8 are expressed and are
      responsible for the conversion of external stimuli to painful sensations. Under
      pathophysiological conditions, excessive activity of TRP-channels leads to
      mechanical allodynia and thermal hyperalgesia. Among the endogenous TRP-channel
      sensitizers, activators and inhibitors, more than 50 arachidonic acid- and
      linoleic acid-metabolites from the COX-, LOX- and CYP-pathways, as well as
      lysophospholipids and isoprenoids can be found. As a consequence, these lipids
      represent the vast majority of endogenous TRP-channel modulators in sensory
      neurons. Although the precise mechanisms of TRP-channel modulation by most lipids
      are still unknown, it became clear that lipids can either bind directly to the
      target TRP-channel or modulate TRP-channels indirectly by activating G-protein
      coupled receptors. Thus, TRP-channels seem to be key sensors for lipids,
      integrating and interpreting incoming signals from the different metabolic lipid
      pathways. Here, we discuss the specific properties of the currently known
      endogenous lipid-derived TRP-channel modulators concerning their ability to
      activate or inhibit TRP-channels, the molecular mechanisms of lipid/TRP-channel
      interactions and specific TRP-regulatory characteristics of the individual lipid
      families. 

PMID- 24287370
TI  - Therapeutic efficacy of a novel nanosomal docetaxel lipid suspension compared
      with taxotere in locally advanced or metastatic breast cancer patients.
AB  - BACKGROUND: Nanosomal docetaxel lipid suspension formulation was developed to
      eliminate ethanol and polysorbate 80 from the currently used docetaxel (Taxotere)
      drug for treatment of cancer patients. NDLS clinical safety and efficacy was
      evaluated and compared with Taxotere at 75 mg/m(2) in metastatic breast cancer
      patients. PATIENTS AND METHODS: A total of 72 patients were randomized in a ratio
      of 2:1 (NDLS:Taxotere). Patients treated with NDLS were not premedicated with
      corticosteroids as required with solvent-based Taxotere. Disease status and tumor
      response was assessed after every 2 cycles of treatment using Response Evaluation
      Criteria in Solid Tumors 1.1 guidelines through cycle 6. RESULTS: Overall
      therapeutic response (complete + partial) rate in metastatic breast cancer
      patients treated with NDLS and Taxotere were 35.5% and 26.3%, respectively,
      indicating better response in patients treated with NDLS. Patients in the NDLS
      group were not premedicated but the safety results of NDLS were found to be
      comparable with Taxotere. CONCLUSION: NDLS formulation with no premedication
      provides an alternative treatment option for breast cancer patients.

PMID- 24287372
TI  - Improving management of patients with autism spectrum disorder having scheduled
      surgery: optimizing practice.
AB  - INTRODUCTION: Surgical preparation for children with autism spectrum disorders
      can be a challenge to perioperative staff because of the unique individual needs
      and behaviors in this population. Most children with autism function best in
      predictable, routine environments, and being in the hospital and other health
      care settings can create a stressful situation. This prospective, descriptive,
      quality improvement project was conducted to optimize best practices for
      perioperative staff and better individualize the plan of care for the autistic
      child and his or her family. METHODS: Forty-three patients with a diagnosis of
      autism or autistic spectrum disorder were seen over 6 months at a suburban
      pediatric hospital affiliated with a major urban pediatric hospital and had an
      upcoming scheduled surgery or procedure requiring anesthesia. Caregivers were
      interviewed before and after surgery to collect information to better help their
      child cope with their hospital visit. RESULTS: In an evaluation of project
      outcomes, data were tabulated and summarized and interview data were
      qualitatively coded for emerging themes to improve the perioperative process for
      the child. DISCUSSION: Findings showed that staff members were able to recognize
      potential and actual stressors and help identify individual needs of surgical
      patients with autism. The families were pleased and appreciative of the
      individual attention and focus on their child's special needs. Investigators also
      found increased staff interest in optimizing the surgical experience for autistic
      children.

PMID- 24287371
TI  - Immune gene discovery in the crucian carp Carassius auratus.
AB  - The crucian carp Carassius auratus (Cyprinidae) is one of the important fish
      species in aquaculture. Although the crucian carp has several economic benefits,
      their immune system and gene information have not been investigated in depth as
      yet. Here, we performed the transcriptome analysis of C. auratus using the
      pyrosequencing method and selected several immune-related genes. Of unigenes
      obtained in this species, we identified a number of immune system-related genes
      (e.g. adhesive protein, antimicrobial protein, apoptosis- and cell cycle-related
      protein, cellular defense effector, immune regulator, pattern recognition
      protein, protease, protease inhibitor, reduction/oxidation-related protein,
      signal transduction-related protein and stress protein) that are potentially
      useful for studies on fish immunity. To be of public and practical use, we
      designed primer pairs of each gene from the crucian carp for real-time RT-PCR
      application and tested the amplicon identity of entire gene sets with the total
      RNA sample. For comparative analysis, we measured tissue-preferential transcript
      profiles of selected genes. This study will be helpful to extend our knowledge on
      the immune system of the crucian carp in comparative aspects and to develop the
      crucian carp as a potential model organism for aquatic quality monitoring in fish
      farming. 

PMID- 24287373
TI  - Expression of caspase activation recruitment and pyrin domain levels of apoptosis
      associated speck-like protein complex in the pancreas of rats subjected to
      experimental pancreatitis: influence of rutin administration.
AB  - The present study investigated the effect of rutin, a natural flavonoid, on the
      expression of caspase activation recruitment domain (CARD) and pyrin domain (PYD)
      of apoptosis-associated speck-like protein (ASC), a mediator of inflammation, in
      the pancreas of rats administered with ethanol (EtOH) and high-fat diet (HFD).
      Pancreatitis was induced in male albino Wistar rats by administering EtOH (8-12
      g/kg/day) and HFD (22% fat) for 90 days. In addition, rats also received 100 mg
      rutin/kg body weight orally from 31st day till the experimental period. Serum
      levels of cytokines, interleukin 18 (IL-18) and IL-6; activity levels of caspase
      1 and myeloperoxidase (MPO); messenger RNA (mRNA) expression of tumor necrosis
      factor alpha (TNF-alpha), caspase-1, CARD and PYD of ASC; and histological
      changes in pancreas were assessed. We observed a significant elevation in serum
      IL-18, IL-6, caspase-1 and MPO activities, mRNA expression of PYD, TNF-alpha and
      caspase-1 in the pancreas of rats administered with EtOH and HFD. Rutin
      administration along with EtOH and HFD significantly upregulated the mRNA
      expression of CARD and downregulated PYD, caspase-1, and TNF-alpha expressions.
      Rutin supplementation was also found to reduce IL-18 and IL-6 levels; and
      inflammatory changes in tissue architecture were evidenced by histological
      observations. The anti-inflammatory activity of rutin might be due to its effect
      on modulating the expression of ASC complex that mediates inflammation. 

PMID- 24287375
TI  - Phase delays to light and gastrin-releasing peptide require the protein kinase A
      pathway.
AB  - Daily photic resetting of the circadian system relies on the transmission of
      light information from the retina to retinorecipient cells within the
      ventrolateral suprachiasmatic nucleus (SCN) core, and subsequent activation of
      rhythmic clock cells in the dorsolateral region. Some neurochemicals such as
      gastrin-releasing peptide (GRP) mimic the phase shifting effects of light and
      induce Ca(2+)-dependent gene expression in the SCN. Activation of the cAMP
      response element binding protein (CREB) is necessary for Ca(2+)-dependent
      transcription to occur and accompanies behavioral phase shifting; however,
      several biochemical cascades are involved in this phenomenon. One pathway that
      has been implicated in photic responses involves protein kinase A (PKA). It is
      not known if this pathway participates in mediating phase shifts to GRP. Here we
      show that preventing PKA activation attenuates both light- and GRP-induced phase
      shifts in locomotor behavior, but only during the early-subjective night. This
      finding demonstrates that activation of PKA is an important component in the
      photic signaling pathway and may mediate GRP output signaling from the SCN core
      to the shell; however, this effect appears to be temporally dependent. 

PMID- 24287374
TI  - Antidepressant effects on serotonin 1A/1B receptors in the rat brain using a gene
      x environment model.
AB  - A gene-environment (GxE) interaction is implicated in both the pathophysiology
      and treatment of major depressive disorder (MDD). This study modeled the effects
      of genetic vulnerability by using the Flinders sensitive line (FSL), a rat model
      of depression and its control counterpart-the Flinders resistant line (FRL). The
      effects of environmental vulnerability (e.g., early-life stress) were modeled by
      using maternal separation. Rats (n=105) were drawn from four groups reflecting
      experimental crossing of strain (FSL vs. FRL) and early-life stress (high vs.
      low) to assess the effects of two antidepressants (escitalopram or nortriptyline)
      compared to vehicle. Quantitative in vitro autoradiography was performed using
      [(125)I]MPPI (5-HT1A) and [(125)I]CYP (5-HT1B) in prefrontal cortex (PFC) and
      hippocampus. Stringent, Bonferroni-corrected statistical analyses showed
      significant strain-by-rearing-by-treatment (three-way) interactions in PFC 5-HT1A
      and hippocampal 5-HT1B receptors. Either vulnerability reduced serotonergic
      binding; no additive effects were associated with the two vulnerabilities. Both
      antidepressants increased hippocampal 5-HT1B receptor binding; however, only
      nortriptyline selectively increased PFC 5-HT1A receptor binding. Taken together,
      our findings demonstrate that antidepressant effects on the serotonergic system
      are shaped by a GxE interaction that depends on antidepressant class and brain
      region. 

PMID- 24287376
TI  - Curcumin promotes neurite outgrowth via reggie-1/flotillin-2 in cortical neurons.
AB  - Curcumin is well known as an antioxidant and anti-inflammatory agent. In this
      study, we provided convincing evidence for the function of curcumin in neurite
      outgrowth of cortical neurons. We discovered that curcumin treatment could
      promote the number of processes, mean process length, and maximum process length
      of primary neurons, which were inhibited by reggie-1 siRNAs or extracellular
      signal-regulated kinase (ERK) 1/2 antagonist. Furthermore, curcumin-induced
      neurite growth was related to the ERK1/2 phosphorylation, which was blocked by
      reggie-1 knockdown. Overall, our results implied that curcumin could mediate
      neurite outgrowth through reggie-1 and ERK1/2 pathway. 

PMID- 24287377
TI  - Stress and withdrawal from d-amphetamine alter 5-HT2A receptor mRNA expression in
      the prefrontal cortex.
AB  - Psychostimulant withdrawal results in emotional, behavioral, and cognitive
      impairments, which may be exacerbated by stress. However, little is known about
      the neurochemical changes that occur when these two conditions are experienced
      concomitantly. 5-HT2A receptor (5-HT2AR) mRNA expression in the prefrontal cortex
      (PFC) is diminished following withdrawal from d-amphetamine (AMPH) and may
      underlie the emotional and cognitive impairments observed in psychostimulant
      withdrawal, but whether stress affects 5-HT2AR mRNA expression during
      psychostimulant withdrawal is unknown. The goal of this study was to examine the
      impact of forced swim test (FST) exposure during AMPH withdrawal on 5-HT2AR mRNA
      expression in PFC. Animals were treated 3 times a day for 4 days with escalating
      doses of AMPH (1-10mg/kg) and 24h or 4 days after the final injection, animals
      were subjected to FST. At 24h of withdrawal, AMPH-treated animals showed greater
      immobility in FST and at 4 days of withdrawal, AMPH-treated animals did not show
      immobility. At 24h of withdrawal, animals showed lower 5-HT2AR mRNA expression in
      the PFC relative to saline-treated animals, and exposure to FST did not further
      decrease expression in these animals. At 4 days of withdrawal, AMPH-treated
      animals showed greater 5-HT2AR mRNA expression relative to saline-treated animals
      in the PFC, an effect that was diminished by exposure to FST. These data indicate
      that stress and short-term AMPH withdrawal affect prefrontal 5-HT2AR mRNA
      expression to a similar degree, and stress experienced during long-term AMPH
      withdrawal can diminish the recovery of 5-HT2AR mRNA expression. Together, these
      data suggest that exposure to stress during extended AMPH withdrawal could
      prolong withdrawal-induced, 5-HT2AR mRNA expression which could be related to 5
      HT2AR mediated deficits. 

PMID- 24287378
TI  - 17beta-estradiol protects cerebellar granule cells against beta-amyloid-induced
      toxicity via the apoptotic mitochondrial pathway.
AB  - Alzheimer's disease (AD) is a well-studied neurodegenerative disorder;
      nevertheless, significant therapeutic agents for the pharmacological treatment of
      this neuropathology are unavailable to date. The toxicity of amyloid beta-peptide
      (Abeta) has been implicated as a critical cause in the development of AD, and
      Abeta-amyloid-induced toxicity is typically associated with apoptosis. Here, we
      investigated the effect of 17beta-estradiol (E2) on Abeta-induced toxicity in
      cerebellar granule cells (CGCs). Our data showed a significant induction of
      apoptosis in neurons treated with Abeta, and the addition of E2 reduced this
      effect. In addition, E2 reduced the Abeta-induced up-regulation of Bax and down
      regulation of Bcl-xL, and inhibited the subsequent mitochondrial release of
      cytochrome c and activation of caspase-3. Moreover, E2 inhibited Abeta-induced c
      Jun N-terminal protein kinase (JNK) activation. Taken together, these findings
      indicate that E2 protects against Abeta-induced apoptosis in neuronal cells by
      preventing mitochondrial dysfunction and interfering with the JNK signalling
      cascade. 

PMID- 24287379
TI  - Cathinone increases body temperature, enhances locomotor activity, and induces
      striatal c-fos expression in the Siberian hamster.
AB  - Cathinone is a beta-keto alkaloid that is the major active constituent of khat,
      the leaf of the Catha edulis plant that is chewed recreationally in East Africa
      and the Middle East. Related compounds, such as methcathinone and mephedrone have
      been increasing in popularity as recreational drugs, resulting in the recent
      proposal to classify khat as a Class C drug in the UK. There is still limited
      knowledge of the pharmacological effects of cathinone. This study examined the
      acute effects of cathinone on core body temperature, locomotor and other
      behaviors, and neuronal activity in Siberian hamsters. Adult male hamsters,
      previously implanted with radio telemetry devices, were treated with cathinone (2
      or 5mg/kg i.p.), the behavioral profile scored and core body temperature and
      locomotor activity recorded by radio telemetry. At the end of the study, hamsters
      received vehicle or cathinone (5mg/kg) and neuronal activation in the brain was
      determined using immunohistochemical evaluation of c-fos expression. Cathinone
      dose-dependently induced significant (p<0.0001) increases in both temperature and
      locomotor activity lasting 60-90min. Cathinone (2mg/kg) increased rearing
      (p<0.02), and 5mg/kg increased both rearing (p<0.001) and lateral head twitches
      (p<0.02). Both cathinone doses decreased the time spent at rest (p<0.001). The
      number of c-fos immunopositive cells were significantly increased in the striatum
      (p<0.0001) and suprachiasmatic nucleus (p<0.05) following cathinone, indicating
      increased neuronal activity. There was no effect of cathinone on food intake or
      body weight. It is concluded that systemic administration of cathinone induces
      significant behavioral changes and CNS activation in the hamster. 

PMID- 24287380
TI  - Greater electroencephalographic coherence between left and right temporal lobe
      structures during increased geomagnetic activity.
AB  - Interhemispheric coherence for 19 channel EEG activity collected over a three
      year period from 184 men and women who relaxed in a quiet, darkened chamber
      showed significant increased coherence between caudal temporal regions for the 11
      Hz frequency band during increased (>~8 nT) global geomagnetic activity at the
      time of measurement. Detailed analyses from source-localization indicated that a
      likely origin was the parahippocampal regions whose net differences at 10, 11 and
      12 Hz intervals were significantly correlated with geomagnetic activity. Analyses
      of residuals to obtain a "purer" measure of parahippocampal contributions
      indicated that interhemispheric temporal lobe coherence across unit increments
      between 1 and 40 Hz revealed the most statistically significant peaks at 7.5 Hz
      and 19.5 Hz. These weak but reliable correlations between global geomagnetic
      activity and the degree of inter-temporal lobe coherence for normal people
      relaxing in a dark, quiet area are consistent with the results of multiple
      studies indicating that intrusive experiences such as "presences" or
      "hallucinations" are more frequent when global geomagnetic activity increases
      above ~15-20 nT.

PMID- 24287381
TI  - Design, synthesis and structure-activity relationships of substituted oxazole
      benzamide antibacterial inhibitors of FtsZ.
AB  - The design, synthesis and structure-activity relationships of a series of oxazole
      benzamide inhibitors of the essential bacterial cell division protein FtsZ are
      described. Compounds had potent anti-staphylococcal activity and inhibited the
      cytokinesis of the clinically-significant bacterial pathogen Staphylococcus
      aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of
      S. aureus harbouring the glycine-to-alanine amino acid substitution at residue
      196 of FtsZ which conferred resistance to previously reported inhibitors in the
      series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the
      pharmacokinetic properties by increasing metabolic stability and provided a
      mechanism for creating pro-drugs. Combining multiple substitutions based on the
      findings reported in this study has provided small-molecule inhibitors of FtsZ
      with enhanced in vitro and in vivo antibacterial efficacy. 

PMID- 24287382
TI  - Identification through structure-based methods of a bacterial NAD(+)-dependent
      DNA ligase inhibitor that avoids known resistance mutations.
AB  - In an attempt to identify novel inhibitors of NAD(+)-dependent DNA ligase (LigA)
      that are not affected by a known resistance mutation in the adenosine binding
      pocket, a detailed analysis of the binding sites of a variety of bacterial
      ligases was performed. This analysis revealed several similarities to the adenine
      binding region of kinases, which enabled a virtual screen of known kinase
      inhibitors. From this screen, a thienopyridine scaffold was identified that was
      shown to inhibit bacterial ligase. Further characterization through structure and
      enzymology revealed the compound was not affected by a previously disclosed
      resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent
      medicinal chemistry program identified substitutions that resulted in an
      inhibitor with moderate activity across various Gram-positive bacterial LigA
      enzymes. 

PMID- 24287383
TI  - Neuroimaging trends and future outlook.
AB  - Imaging equipment is experiencing advances in speed, sensitivity, safety, and
      workflow. There is an increasing trend toward physiologic imaging and
      quantitation, requiring greater consistency across manufacturers and clinics. The
      Human Connectome Project is symbolic of the drive toward combining multimodality
      anatomic and functional imaging with quantitation and sophisticated atlases.
      Advanced visualization methods have become essential in the evaluation of large
      multidimensional data sets. Hybrid imaging blends advantages from multiple
      modalities to provide a comprehensive anatomic, functional, physiologic, and
      metabolic data set. Breakthrough clinical neuroimaging applications are derived
      from an alignment of scientific, engineering, clinical, and business conditions. 

PMID- 24287384
TI  - Advanced neuroimaging of mild traumatic brain injury.
AB  - This article focuses on advancements in neuroimaging techniques, compares the
      advantages of each of the modalities in the evaluation of mild traumatic brain
      injury, and discusses their contribution to our understanding of the
      pathophysiology as it relates to prognosis. Advanced neuroimaging techniques
      discussed include anatomic/structural imaging techniques, such as diffusion
      tensor imaging and susceptibility-weighted imaging, and functional imaging
      techniques, such as functional magnetic resonance imaging, perfusion-weighted
      imaging, magnetic resonance spectroscopy, and positron emission tomography. 

PMID- 24287385
TI  - Neuroimaging of dementia.
AB  - Dementia, whether secondary to Alzheimer disease or another process, is a
      significant cause of morbidity and mortality worldwide. Although dementia remains
      a clinical diagnosis, for many years imaging has served as a key component in the
      assessment of patients with cognitive impairment. There have been tremendous
      advancements in the neuroimaging of dementia over the past decade, moving the
      field past the rule-out dogma toward ruling in specific pathophysiologic
      processes. This article is written for the practicing clinician, to provide a
      review of neuroimaging findings associated with selected degenerative and
      nondegenerative forms of dementia. 

PMID- 24287386
TI  - Imaging of Chiari type I malformation and syringohydromyelia.
AB  - Chiari malformations are anatomic anomalies that comprise a broad spectrum of
      neurologic conditions. The most common malformation, a Chiari type I
      malformation, can present with a variety of signs and symptoms, most frequently
      an occipital Valsalva-induced headache. Cranial and spinal magnetic resonance
      (MR) imaging is used to identify the degree of tonsillar descent and document the
      presence of syringohydromyelia. The advent of cine-MR flow imaging (cine as in
      "cinema") has provided new insight as to the dynamic process involved in the
      evolution of this pathophysiology. This article reviews the neuroimaging of this
      fascinating disorder.

PMID- 24287387
TI  - Neuroimaging of infectious disease.
AB  - This article provides an imaging overview of several of the common central
      nervous system (CNS) infections. Neurologic clinicians who provide acute care for
      patients should be familiar with the range of imaging findings for patients with
      acute neurologic infections, including knowledge of the appropriate study and the
      best protocol and views to show the disorder, and the ability to properly
      interpret them. This requirement applies particularly for CNS infections, as in
      stroke, in which a rapid appreciation of the exact cause of a patient's infection
      may play a major role in reducing mortality and morbidity. 

PMID- 24287388
TI  - Imaging of cancer therapy-induced central nervous system toxicity.
AB  - Cancer therapy, including radiation and chemotherapy, can be associated with
      harmful effects to the central nervous system. Recognition of classical
      neurotoxic syndromes is critical to appropriately guide and optimize patient
      management. As a result of cancer therapy-induced toxicity, patients may present
      with acute, subacute, and chronic neurologic symptoms that can be misinterpreted
      as tumor recurrence, infection, or paraneoplastic syndromes. In this review the
      advantages and limitations of various neuroimaging modalities such as computed
      tomography, magnetic resonance imaging, and positron emission tomography,
      frequently used in patients with cancer who present with diverse neurotoxic
      syndromes, are highlighted. 

PMID- 24287389
TI  - Neuroimaging of neurocutaneous diseases.
AB  - An in-depth knowledge of the imaging characteristics of the common neurocutaneous
      diseases (NCD) described in this article will help neurologists understand the
      screening imaging modalities in these patients. The future of neuroimaging is
      geared towards developing and refining magnetic resonance imaging (MRI)
      sequences. The detection of tumors in NCD has greatly improved with availability
      of high-field strength 3T MRI machines. Neuroimaging will remain at the heart and
      soul of the multidisciplinary care of such complex diagnoses to guide early
      detection and monitor treatment. 

PMID- 24287391
TI  - Imaging and decision-making in neurocritical care.
AB  - Critically ill neurologic patients are common in the hospital practice of
      neurology and are often in extreme states requiring accurate and specific
      information. Imaging, especially using advanced imaging techniques, can provide
      an important means of garnering this information. This article focuses on the
      clinical utilization of selective imaging methods that are commonly used in
      critically ill neurologic patients to render diagnoses, to monitor effects of
      treatment, or have contributed to a better understanding of pathophysiology in
      the intensive care unit. 

PMID- 24287390
TI  - Imaging of cerebral ischemia: from acute stroke to chronic disorders.
AB  - Cerebral ischemia manifests widely in patient symptoms. Along with the clinical
      examination, imaging serves as a powerful tool throughout the course of ischemia
      from acute onset to evolution. A thorough understanding of imaging modalities,
      their strengths and their limitations, is essential for capitalizing on the
      benefit of this complementary source of information for understanding the
      mechanism of disease, making therapeutic decisions, and monitoring patient
      response over time. 

PMID- 24287392
TI  - Novel multimodality imaging techniques for diagnosis and evaluation of
      arteriovenous malformations.
AB  - Brain arteriovenous malformations (AVMs) are abnormal communications between
      arteries and veins characterized radiographically by the presence of a nidus and
      early venous drainage. Estimation of hemorrhage risk and determination of
      treatment strategy rely on the location and hemodynamic properties of the AVM.
      This article describes modern noninvasive approaches to diagnosing and evaluating
      AVMs, including dynamic 4-dimensional computed tomographic and magnetic resonance
      angiography and perfusion imaging. The role and latest advances in digital
      subtraction angiography and intraoperative imaging are also described. 

PMID- 24287393
TI  - Neurologic applications of whole-brain volumetric multidetector computed
      tomography.
AB  - The introduction of computed tomography (CT) scanning in the 1970s revolutionized
      the way clinicians could diagnose and treat stroke. Subsequent advances in CT
      technology significantly reduced radiation dose, reduced metallic artifact, and
      achieved speeds that enable dynamic functional studies. The recent addition of
      whole-brain volumetric CT perfusion technology has given clinicians a powerful
      tool to assess parenchymal perfusion parameters as well as visualize dynamic
      changes in blood vessel flow throughout the brain during a single cardiac cycle.
      This article reviews clinical applications of volumetric multimodal CT that
      helped to guide and manage care. 

PMID- 24287395
TI  - Follow-up to the 2009 Neurologic Clinics, Neuroimaging edition. Preface.

PMID- 24287394
TI  - Magnetic resonance-guided focused ultrasound: a new technology for clinical
      neurosciences.
AB  - Transcranial MRI-guided focused ultrasound (TcMRgFUS) is an old idea but a new
      technology that may change the entire clinical field of the neurosciences.
      TcMRgFUS has no cumulative effect, and it is applicable for repeatable
      treatments, controlled by real-time dosimetry, and capable of immediate tissue
      destruction. Most importantly, it has extremely accurate targeting and constant
      monitoring. It is potentially more precise than proton beam therapy and
      definitely more cost effective. Neuro-oncology may be the most promising area of
      future TcMRgFUS applications.

PMID- 24287396
TI  - Multidetector computerized tomography enema versus magnetic resonance enema in
      the diagnosis of rectosigmoid endometriosis.
AB  - PURPOSE: To compare the accuracy of multidetector computerized tomography enema
      (MDCT-e) and magnetic resonance enema (MRI-e) in determining the presence of
      sigmoid and rectal endometriotic nodules. MATERIALS AND METHODS: 260 women (32.6
      +/- 4.3 years) with symptoms suggestive of rectosigmoid endometriosis underwent
      MDCT-e and MRI-e prior to laparoscopy. After retrograde colonic distention and
      injection of intravenous contrast medium, patients were scanned on a 64-row MDCT
      scanner. MRI-e was performed on a 1.5T magnet using an 8 channels phased array
      coil; intestinal distention was achieved by introducing in the rectum 250-300 ml
      of ultrasonographic gel diluted with saline solution. Radiological findings were
      compared with surgical and histological results. RESULTS: 176 women had
      rectosigmoid endometriosis at surgery. There was no significant difference in the
      accuracy of MDCT-e (98.5%) and MRI-e (96.9%) in the diagnosis of sigmoid and
      rectal endometriosis (p=0.248). The sensitivity, specificity, positive predictive
      value, negative predictive value, positive likelihood ratio and negative
      likelihood ratio of MDCT-e and MRI-e were respectively 98.3%, 98.8%, 99.4%,
      96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. CONCLUSIONS: Both
      MDCT-e and MRI-e are accurate in the diagnosis of rectal and sigmoid
      endometriosis.

PMID- 24287397
TI  - Electrospun silk-elastin-like fibre mats for tissue engineering applications.
AB  - Protein-based polymers are present in a wide variety of organisms fulfilling
      structural and mechanical roles. Advances in protein engineering and recombinant
      DNA technology allow the design and production of recombinant protein-based
      polymers (rPBPs) with an absolute control of its composition. Although the
      application of recombinant proteins as biomaterials is still an emerging
      technology, the possibilities are limitless and far superior to natural or
      synthetic materials, as the complexity of the structural design can be fully
      customized. In this work, we report the electrospinning of two new genetically
      engineered silk-elastin-like proteins (SELPs) consisting of alternate silk- and
      elastin-like blocks. Electrospinning was performed with formic acid and aqueous
      solutions at different concentrations without addition of further agents. The
      size and morphology of the electrospun structures was characterized by scanning
      electron microscopy showing its dependence on the concentration and solvent used.
      Treatment with methanol-saturated air was employed to stabilize the structure and
      promote water insolubility through a time-dependent conversion of random coils
      into beta-sheets (FTIR). The resultant methanol-treated electrospun mats were
      characterized for swelling degree (570-720%), water vapour transmission rate
      (1083 g/m(2)/day) and mechanical properties (modulus of elasticity ~126 MPa).
      Furthermore, the methanol-treated SELP fibre mats showed no cytotoxicity and were
      able to support adhesion and proliferation of normal human skin fibroblasts.
      Adhesion was characterized by a filopodia-mediated mechanism. These results
      demonstrate that SELP fibre mats can provide promising solutions for the
      development of novel biomaterials suitable for tissue engineering applications. 

PMID- 24287399
TI  - Generalized mathematical representation of the soft tissue artefact.
AB  - While reconstructing skeletal movement using stereophotogrammetry, the relative
      movement between a skin marker and the underlying bone is regarded as an artefact
      (soft tissue artefact: STA). Similarly, the consequent pose, size and shape
      variations that affect a cluster of markers associated with a bony segment, or
      any arbitrary change of configuration in the marker local positions as
      representative of the skin envelope shape variation, may also be looked upon as
      an STA. Bone pose estimators able to compensate for these artefacts must embed
      relevant a priori knowledge in the form of an STA mathematical model. Prior to
      tackling this modeling exercise, an appropriate definition and mathematical
      representation of the STA time histories must be accomplished. Relevant
      appropriateness is based on the degree of approximation of the STA reconstruction
      and on the number of parameters involved. The objective of this study was to
      propose a generalized mathematical representation of the STA which would be
      applicable for most plausible definitions of it. To this purpose, a modal
      approach was used that, most importantly, allows for the splitting of a given STA
      into additive components (modes). For each STA definition, these modes may be
      ranked according to the contribution that each of them gives to the
      reconstruction of the STA. In this way, the STA definition leading to the minimum
      number of modes, and, therefore, of parameters, that provides an adequate
      approximation for further purposes can be selected, allowing a trade-off between
      complexity and effectiveness of the STA model. Using information available in the
      literature and data provided by an ex-vivo experiment, it is shown that the modes
      corresponding to the different STA definitions (individual marker displacements,
      marker-cluster geometrical transformations, and skin envelope shape variations)
      can be ranked and selected leading, respectively, to a large, moderate or low
      number of parameters embedded in the STA mathematical representation. 

PMID- 24287398
TI  - Claudin-2 is an independent negative prognostic factor in breast cancer and
      specifically predicts early liver recurrences.
AB  - BACKGROUND: Predicting any future metastatic site of early-stage breast cancer is
      important as it significantly influences the prognosis of advanced disease. This
      study aimed at investigating the potential of claudin-2, over-expressed in breast
      cancer liver metastases, as a biomarker for predicting liver metastatic
      propensity in primary breast cancer. METHODS: Claudin-2 expression was analyzed
      in two independent cohorts. Cohort 1 included 304 women with metastatic breast
      cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal
      women with early-stage node-negative breast cancer diagnosed between 1991 and
      1994. Global transcriptional profiling of fine-needle aspirates from metastases
      was performed, followed by immunohistochemical analyses in archival primary tumor
      tissue. Associations between claudin-2 expression and relapse site were assessed
      by univariable and multivariable Cox regression models including conventional
      prognostic factors. Two-sided statistical tests were used. RESULTS: CLDN2 was
      significantly up-regulated (P < 0.001) in liver metastases compared to other
      metastatic sites. Claudin-2 protein was more frequently expressed in primary
      tumors from patients who subsequently developed liver metastases (P = 0.02) and
      high expression was associated with a shorter metastasis-free interval (cohort 1,
      HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically,
      a significantly shorter interval between primary tumor diagnosis and liver
      specific recurrence was observed among patients with high levels of claudin-2
      expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9).
      CONCLUSION: These results suggest a novel role for claudin-2 as a prognostic
      biomarker with the ability to predict not only the likelihood of a breast cancer
      recurrence, but more interestingly, the liver metastatic potential of the primary
      tumor.

PMID- 24287400
TI  - The exoskeletal structure and tensile loading behavior of an ant neck joint.
AB  - Insects have evolved mechanical form and function over millions of years. Ants,
      in particular, can lift and carry heavy loads relative to their body mass. Loads
      are lifted with the mouthparts, transferred through the neck joint to the thorax,
      and distributed over six legs and tarsi (feet) that anchor to the supporting
      surface. While previous research has explored attachment mechanisms of the tarsi,
      little is known about the relation between the mechanical function and the
      structural design and material properties of the ant. This study focuses on the
      neck--the single joint that withstands the full load capacity. We combine
      mechanical testing, computed tomography (CT), scanning electron microscopy (SEM),
      and computational modeling to better understand the mechanical structure-function
      relation of the neck joint of the ant species Formica exsectoides (Allegheny
      mound ant). Our mechanical testing results show that the soft tissue forming the
      neck joint of F. exsectoides exhibits an elastic modulus of 230+/-140 MPa and can
      withstand ~5000 times the ant's weight. We developed a 3-dimensional (3D) model
      of the structural components of the neck joint for simulation of mechanical
      behavior. Finite element (FE) simulations reveal the neck-to-head transition
      where the soft membrane material meets the hard exoskeleton as the critical point
      for failure of the neck joint, which is consistent with our experiments. Our
      results further indicate that the neck joint structure exhibits anisotropic
      mechanical behavior with the highest stiffness occurring when the load path is
      aligned with the axis of the neck.

PMID- 24287401
TI  - The effect of unstable loading versus unstable support conditions on spine
      rotational stiffness and spine stability during repetitive lifting.
AB  - Lumbar spine stability has been extensively researched due to its necessity to
      facilitate load-bearing human movements and prevent structural injury. The nature
      of certain human movement tasks are such that they are not equivalent in levels
      of task-stability (i.e. the stability of the external environment). The goal of
      the current study was to compare the effects of dynamic lift instability,
      administered through both the load and base of support, on the dynamic stability
      (maximal Lyapunov exponents) and stiffness (EMG-driven model) of the lumbar spine
      during repeated sagittal lifts. Fifteen healthy males performed 23 repetitive
      lifts with varying conditions of instability at the loading and support
      interfaces. An increase in spine rotational stiffness occurred during unstable
      support scenarios resulting in an observed increase in mean and maximum Euclidean
      norm spine rotational stiffness (p=0.0011). Significant stiffening effects were
      observed in unstable support conditions about all lumbar spine axes with the
      exception of lateral bend. Relative to a stable control lifting trial, the
      addition of both an unstable load as well as an unstable support did not result
      in a significant change in the local dynamic stability of the lumbar spine
      (p=0.5592). The results suggest that local dynamic stability of the lumbar spine
      represents a conserved measure actively controlled, at least in part, by trunk
      muscle stiffening effects. It is evident therefore that local dynamic stability
      of the lumbar spine can be modulated effectively within a young-healthy
      population; however this may not be the case in a patient population. 

PMID- 24287402
TI  - How to encourage smokers to participate in web-based computer-tailored smoking
      cessation programs: a comparison of different recruitment strategies.
AB  - The reach, retention and costs of four strategies aimed to recruit smokers for
      participation in a computer-tailored smoking cessation intervention was explored.
      The study was part of a randomized controlled trial whereby 832 respondents were
      randomized to three conditions. Smokers were invited by general practitioners
      (GPs), newspapers, Internet and other strategies (i.e. mailing organizations) to
      take part. ANOVA's/Chi-square tests explored sample differences. Logistic
      regression analyses investigated differences between the samples regarding
      retention and smoking behaviour. Smokers recruited via GPs (N = 144) had a lower
      educational level and suffered more from chronic obstructive pulmonary disease
      compared with respondents recruited via Internet (N = 307) (chi(2) = 11.554, df =
      3, P = 0.009). Less motivated respondents recruited by GPs were more likely to
      return to study compared with the less motivated respondents recruited by 'other
      recruitment' strategies (chi(2) = 6.416, df = 3, P = 0.093). Highly addicted
      respondents recruited from newspapers (N = 213) were less likely to make a quit
      attempt compared with highly addicted respondents recruited by GPs (OR = 0.334, P
      = 0.035). Females from newspapers were less likely to remain abstinent compared
      with the GP sample (OR = 0.337, P = 0.005). Recruitment via GPs showed highest
      costs. Recruitment strategy influenced the type of smokers. Group differences
      were associated with different patterns of quitting. 

PMID- 24287404
TI  - Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without
      compromising insulin-sensitizing effects in mice.
AB  - Much concern has arisen regarding critical adverse effects of thiazolidinediones
      (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD
      induced cardiac hypertrophy (CH) has been attributed to an increase in plasma
      volume or a change in cardiac nutrient preference, causative roles have not been
      established. To test the hypothesis that volume expansion directly mediates
      rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and
      cardiac and metabolic consequences were examined. Rosiglitazone treatment induced
      volume expansion and CH in wild-type and PPARgamma heterozygous knockout
      (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)).
      Cotreatment with the diuretic furosemide in wild-type mice attenuated
      rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte
      apoptosis, hypertrophy-related signal activation, and left ventricular
      dysfunction. Similar changes were observed in mice treated with pioglitazone. The
      diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated
      rosiglitazone effects on volume expansion and CH. Interestingly, expression of
      glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but
      these changes were not attenuated by furosemide cotreatment. Importantly,
      rosiglitazone-mediated whole-body metabolic improvements were not affected by
      furosemide cotreatment. We conclude that releasing plasma volume reduces adverse
      effects of TZD-induced volume expansion and cardiac events without compromising
      TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. 

PMID- 24287406
TI  - Voltammetric behavior of uric acid on carbon paste electrode modified with salmon
      sperm dsDNA and its application as label-free electrochemical sensor.
AB  - A simple and sensitive label-free electrochemical DNA biosensor was proposed for
      the rapid determination of uric acid (UA) using a carbon nano tube paste
      electrode (CNTPE) modified with salmon sperm dsDNA. At first, the interaction
      between UA and the DNA was studied using differential pulse voltammetry (DPV).
      The addition of the DNA to UA solution resulted in a decrease in the peak current
      of UA and at the same time, a positive shift in the peak potential indicating an
      intercalative interaction. Then, the voltammetric response of a DNA-immobilized
      CNTPE was investigated for the determination of UA. The immobilization of the DNA
      was carried out using acid-functionalized carbon nanotubes and studied using
      Fe(CN)6(3-)/Fe(CN)6(4-) redox indicator. Compared with unmodified CNTPE, the
      oxidation signal of UA showed a significant increase at the DNA-coated electrode,
      and shifted to more positive potentials attributed to the pre-concentration of UA
      at the electrode surface due to interaction with the surface-confined DNA layer.
      This interaction was used for the fabrication of a simple and sensitive biosensor
      for determining UA. After the optimization of operational parameters, a linear
      dependence of the peak current on the UA concentration was observed in the range
      of 7.0*10(-7) to 1.1*10(-4) mol L(-1), with the detection and quantification
      limits of 1.8*10(-7) and 5.8*10(-7) mol L(-1), respectively. The proposed
      biosensor was successfully applied to validate its capability for the analysis of
      UA in human serum and urine samples.

PMID- 24287405
TI  - Critical role of the mTOR pathway in development and function of myeloid-derived
      suppressor cells in lal-/- mice.
AB  - Lysosomal acid lipase (LAL) is essential for the hydrolysis of cholesteryl esters
      and triglycerides to generate cholesterol and free fatty acids in cellular
      lysosomes. Ablation of the lal gene (lal(-/-)) systemically increased expansion
      of cluster of differentiation molecule 11b (CD11b), lymphocyte antigen 6G (Ly6G)
      myeloid-derived suppressor cells (MDSCs) that caused myeloproliferative neoplasms
      in mice. Study of lal(-/-) bone marrow Ly6G(+) MDSCs via transcriptional
      profiling showed increases in mammalian target of rapamycin (mTOR) signaling
      pathway transcripts. Injection of mTOR pharmacologic inhibitors into lal(-/-)
      mice significantly reduced bone marrow myelopoiesis and systemic CD11b(+)Ly6G(+)
      cell expansion. Rapamycin treatment of lal(-/-) mice stimulated a shift from
      immature CD11b(+)Ly6G(+) cells to CD11b(+) single-positive cells in marrow and
      tissues and partially reversed the increased cell proliferation, decreased
      apoptosis, increased ATP synthesis, and increased cell cycling of bone marrow
      CD11b(+)Ly6G(+) cells obtained from lal(-/-) mice. Pharmacologic and siRNA
      suppression of mTOR, regulatory-associated protein of mTOR, rapamycin-insensitive
      companion of mTOR, and Akt1 function corrected CD11b(+)Ly6G(+) cell in lal(-/-)
      mice development from Lin(-) progenitor cells and reversed the immune suppression
      on T-cell proliferation and function in association with decreased reactive
      oxygen species production, and recovery from impairment of mitochondrial membrane
      potential compared with control mutant cells. These results indicate a crucial
      role of LAL-regulated mTOR signaling in the production and function of
      CD11b(+)Ly6G(+) cells. The mTOR pathway may serve as a novel target to modulate
      the emergence of MDSCs in those pathophysiologic states in which these cells play
      an immunosuppressive role. 

PMID- 24287407
TI  - Aptamer biosensor for sensitive detection of toxin A of Clostridium difficile
      using gold nanoparticles synthesized by Bacillus stearothermophilus.
AB  - A sensitive electrochemical biosensor was developed to detect toxin A (TOA) of
      Clostridium difficile based on an aptamer selected by the systematic evolution of
      ligands using exponential enrichment and gold nanoparticles (GNPS) synthesized by
      Bacillus stearothermophilus. The thiolated single-stranded DNA used as the
      capture probe (CP) was first self-assembled on a Nafion-thionine-GNPS-modified
      screen-printed electrode (SPE) through an Au-thiol interaction. The horseradish
      peroxidase (HRP)-labeled aptamer probe (AP) was then hybridized to the
      complementary oligonucleotide of CP to form an aptamer-DNA duplex. In the absence
      of TOA, the aptamer-DNA duplex modified the electrode surface with HRP, so that
      an amperometric response was induced based on the electrocatalytic properties of
      thionine. This was mediated by the electrons that were generated in the enzymatic
      reaction of hydrogen peroxide under HRP catalysis. After the specific recognition
      of TOA, an aptamer-TOA complex was produced rather than the aptamer-DNA duplex,
      forcing the HRP-labeled AP to dissociate from the electrode surface, which
      reduced the catalytic capacity of HRP and reduced the response current. The
      reduction in the response current correlated linearly with the concentration of
      TOA in the range of 0-200 ng/mL. The detection limit was shown to be 1 nM for
      TOA. This biosensor was applied to the analysis of TOA and showed good
      selectivity, reproducibility, stability, and accuracy.

PMID- 24287408
TI  - Hydrogel with chains functionalized with carboxyl groups as universal 3D platform
      in DNA biosensors.
AB  - Application of hydrogel based on N-isopropylacrylamide with carboxyl groups
      grafted to the chains enabled the immobilization of DNA at an extent exceeding
      that for flat surfaces by at least one order of magnitude. The probe DNA strands
      in the 3D platform were fully available for the hybridization process. The
      examination of the gels containing different amounts of grafted carboxyl groups
      (1-10%) was done using quartz crystal microbalance, electrochemical impedance
      spectroscopy, chronoamperometry and ionic coupled plasma with laser ablation. The
      optimal carboxyl group content was determined to be 5%. A very good agreement of
      the data obtained with independent techniques on content of DNA in the gel was
      obtained. In comparison to the other methods of immobilization of DNA the new
      platform enabled complete removal of DNA after the measurements and analysis and,
      therefore, could be used many times. After a 10-fold exchange of the DNA-sensing
      layer the efficiency of hybridization and analytical signal did not change by
      more than 5%. The sensor response increased linearly with logarithm of
      concentration of target DNA in the range 1*10(-13)-1*10(-6) M. The obtained
      detection limit was circa 8*10(-13) M of target DNA in the sample which is a
      substantial improvement over the planar sensing layers.

PMID- 24287409
TI  - Development of first generation in-situ pathogen detection system (Gen1-IPDS)
      based on NanoGene assay for near real time E. coli O157:H7 detection.
AB  - We developed the first generation in-situ pathogen detection system (Gen1-IPDS)
      based on the NanoGene assay for detecting and quantifying Escherichia coli
      O157:H7 specific eaeA gene. The NanoGene assay employs the hybridization of
      target DNA with quantum dot labeled magnetic beads and probe DNAs to detect and
      quantify the target bacterial gene. The Gen1-IPDS is currently capable of
      executing four key steps required in the NanoGene assay: sample and reagents
      introduction, DNA hybridization, magnetic separation of complexes, and sample
      collection. Operational parameters such as magnet position, hybridization buffer
      composition, hybridization flow rate, and hybridization temperature were
      investigated. Using the experimentally determined operational parameters, the
      target gene was successfully quantified (R(2)=0.97) over a range of six orders of
      magnitude (10(-12) to 10(-6) mol L(-1)). The limit of detection (LOD) was
      determined to be 49*10(-15) mol L(-1). The specificity was also demonstrated by
      the differential discrimination of mismatched target DNAs. The NanoGene assay
      quantification results via Gen1-IPDS were validated by correlation with its
      laboratory version (R(2)=0.97).

PMID- 24287410
TI  - Effective signal-on photoelectrochemical immunoassay of subgroup J avian leukosis
      virus based on Bi2S3 nanorods as photosensitizer and in situ generated ascorbic
      acid for electron donating.
AB  - A universal and effective photoelectrochemical (PEC) immunosensing device was
      fabricated on an indium tin oxide (ITO) electrode for sensitive and specific
      detection of subgroup J of avian leukosis virus (ALVs-J) based on a signal-on
      strategy. Bismuth sulfide (Bi2S3) nanorods, with good morphology, high
      crystallinity and differentiated PEC properties, were selected as the
      photoelectrochemical species and synthesized by a facile hydrothermal method. On
      the basis of alkaline phosphatase catalytic chemistry to in situ produce ascorbic
      acid for electron donating, an enhanced photocurrent was obtained. Due to the
      dependence of the photocurrent signal on the concentration of generated electron
      donor, an exquisite immunosandwich protocol was successfully constructed for PEC
      detection of ALVs-J with a linear range from 10(2.14) to 10(3.65) TCID50/mL. The
      detection limit was 10(2.08) TCID50/mL (S/N=3), and high stability and
      specificity were obtained. The strategy provides a fast and sensitive method for
      ALVs-J analysis and opens a general format for future development of PEC
      immunoanalysis.

PMID- 24287411
TI  - Investigation of the effect of phytohormone on the expression of microRNA-159a in
      Arabidopsis thaliana seedlings based on mimic enzyme catalysis systematic
      electrochemical biosensor.
AB  - MicroRNAs (miRNAs) play very important roles in plant growth and development as
      well as phytohormones. More importantly, microRNAs were recently found to be a
      new growth regulator involved in plant hormone signaling. Therefore, for
      investigating the expression change of microRNAs in plants exposed to
      phytohormones and understanding the effect of phytohormones on microRNAs
      expression, we developed a simple, sensitive, and label-free method for microRNAs
      biosensing based on mimic enzyme catalysis signal amplification, where carboxylic
      graphene-hemin hybrid nanosheets was synthesized and used to catalyze the
      oxidation reaction of hydroquinone in the presence of H2O2 due to the intrinsic
      peroxidase-like activity of hemin on the carboxylic graphene surface. The
      electrochemical reduction current of the oxidative product of benzoquinone was
      depended on the hybridization amount of microRNAs and used to monitor the
      microRNAs hybridization event. Under optimal detection conditions, the current
      response was proportional to the logarithm concentration of microRNA-159a from
      0.5 pM to 1.0 nM with the detection limit of 0.17 pM (S/N=3). The fabricated
      biosensor showed highly reproducible (Relative standard deviation (RSD) was 3.53%
      for 10 biosensors fabricated independently) and detection selectivity (Even
      discriminating single-base mismatched microRNA sequence). We also found that
      abscisic acid, a kind of phytohormone, had greatly influence on microRNA-159a
      expression in Arabidopsis thaliana seedlings. With increasing abscisic acid
      concentration and prolonging incubation time, both the expression level of
      microRNA-159a increased. This graphene-hemin-based approach provides a novel
      avenue to detect microRNA with high sensitivity and selectivity while avoiding
      laborious label, disadvantages of bio-enzymes and complex operations for
      microRNAs separation and enrichment, which might be attractive for genetic
      analysis and clinic biomedical application.

PMID- 24287412
TI  - Nickel oxide hollow microsphere for non-enzyme glucose detection.
AB  - A facile strategy has been developed to fabricate nickel oxide hollow
      microspheres (NiO-HMSs) through a solvothermal method by using a mixed solvent of
      ethanol and water with the assistance of sodium dodecyl sulfate (SDS). Various
      techniques, including transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), and powder X-ray diffraction (XRD), were used to characterize
      the morphology and the structure of as-prepared samples. It was confirmed that
      the products possess a hollow microsphere structure that is constructed by
      interconnecting porous nanoplate framework. Electrochemical studies indicate that
      the NiO-HMS exhibits excellent stability and high catalytic activity for
      electrocatalytic oxidation of glucose in alkaline solutions, which enables the
      NiO-HMS to be used in enzyme-free amperometric sensors for glucose determination.
      It was demonstrated that the NiO-HMS-based glucose biosensor offers a variety of
      merits, such as a wide linear response window for glucose concentrations of 1.67
      MUM-6.87 mM, short response time (3 s), a lower detection limit of 0.53 MUM
      (S/N=3), high sensitivity (~2.39 mA mM(-1) cm(-2)) as well as good stability and
      repeatability.

PMID- 24287413
TI  - Electrochemical sensor based on magnetic molecularly imprinted nanoparticles at
      surfactant modified magnetic electrode for determination of bisphenol A.
AB  - A selective electrochemical sensor based on magnetic molecularly imprinted
      nanoparticles was developed for determination of bisphenol A (BPA). The particles
      with regular morphology, high saturation magnetization and good monodispersion
      were prepared. The hydrophilicity, sensitivity and anti-fouling of the sensor
      were enhanced by modifying carbon paste electrode with surfactant CTAB in
      advanced. The results demonstrated that the response of BPA on imprinted
      electrode was 2.6 times as much as that on non-imprinted sensor. Moreover, the
      separation factors of BPA to beta-estradiol, estriol and diethylstilbestrol were
      16.5, 17.3 and 6.6, respectively. Under optimized conditions, the currents were
      found to be proportional to the BPA concentrations in the range of 6.0*10(-7)
      1.0*10(-4) mol/L with a detection limit of 1.0*10(-7) mol/L (S/N=3). A rapid
      response of the imprinted sensor was obtained within 3 min. The developed sensor
      was successfully used for determination of BPA in actual samples such as drink
      bottles and lake water.

PMID- 24287414
TI  - Advantages of fluorescent microspheres compared with colloidal gold as a label in
      immunochromatographic lateral flow assays.
AB  - Label selection is of vital importance for immunochromatographic assays. In this
      study, the fluorescent microsphere test strip and colloidal gold
      immunochromatographic test strip (FM-ICTS and CG-ICTS) were developed for the
      detection of Escherichia coli O157:H7 on the basis of the sandwich format. Two
      types of labels, namely, colloidal gold particles (CG) and carboxyl-modified
      fluorescent microspheres (FMs), were compared while coupling with anti-E. coli
      O157:H7 monoclonal antibody (mAb). The FM-ICTS and CG-ICTS were also compared.
      Results show that the coupling rate between FMs and mAb was higher than that
      between CG and mAb. Under optimum conditions, the sensitivity of FM-ICTS was
      eight times higher than that of CG-ICTS. Approximately 0.1 MUg of mAb was used in
      every FM-ICTS, whereas 0.4 MUg of mAb was used in every CG-ICTS. The coefficient
      of variation of FM-ICTS and CG-ICTS was 4.8% and 16.7%, respectively. The FM-ICTS
      and CG-ICTS can be stored at room temperature for 12 months and specific to five
      E. coli O157:H7 strains. Milk sample inoculated with E. coli O157:H7 were tested
      by the FM-ICTS and CG-ICTS. The FM-ICTS sensitivity was 10(4) CFU/ml while the CG
      ICTS sensitivity was 10(5) CFU/ml. The sensitivity, consumption of antibodies,
      and coefficient of variation of FM-ICTS were better than those of CG-ICTS for the
      detection of E. coli O157:H7.

PMID- 24287415
TI  - Epitope imprinted polymer coating CdTe quantum dots for specific recognition and
      direct fluorescent quantification of the target protein bovine serum albumin.
AB  - A novel epitope molecularly imprinted polymer (EMIP) for specific recognition and
      direct fluorescent quantification of the target protein bovine serum albumin
      (BSA) was demonstrated where polymerization was performed on the surface of
      silica nanospheres embedded CdTe quantum dots (QDs). The synthetic peptide
      derived from the surface-exposed C-terminus of bovine serum albumin (BSA,
      residues 599-607) was selected as the template molecule. The resulting EMIP film
      was able to selectively capture the template peptide and the corresponding target
      protein BSA via the recognition cavities. Based on the fluorescence quenching,
      the EMIP-coated QDs (molecular imprinted polymer coating CdTe QDs using epitope
      as the template) nanospheres were successfully applied to the direct fluorescence
      quantification of BSA. Compared with BMIP-coated QDs (molecular imprinted polymer
      coating CdTe QDs using BSA as the template), the imprinting factor and adsorption
      capacity of EMIP-coated QDs were greatly increased. The prepared EMIP-coated QDs
      can also discriminate even one mismatched sequences from the original sequences
      of the epitope of the BSA. The practical analytical performance of the EMIP
      coated QDs was examined by evaluating the detection of BSA in the bovine calf
      serum sample with satisfactory results. In addition, the resulting EMIP-coated
      QDs nanospheres were also successfully applied to separating BSA from the bovine
      blood sample. 

PMID- 24287416
TI  - Enhanced non-enzymatic glucose sensing based on copper nanoparticles decorated
      nitrogen-doped graphene.
AB  - Copper nanoparticles (NPs) decorated nitrogen-doped graphene (Cu-N-G) was
      prepared by a facile thermal treatment, and further employed as a novel sensing
      material for fabricating the sensitive non-enzymatic glucose sensor. Compared
      with pure Cu NPs, the Cu-N-G showed enhanced electrocatalytic activity to glucose
      oxidation due to the integration of N-G, which exhibited the oxidation peak
      current of glucose ca. 23-fold higher than that of pure Cu NPs. The presented
      sensor showed excellent performances for glucose detection including wide linear
      range of 0.004-4.5 mM, low detection limit (1.3 MUM, S/N=3), high sensitivity
      (48.13 MUA mM(-1)), fast response time (<5 s), good selectivity to the general
      coexisted interferences, etc. Such properties would promote the potential
      application of the nitrogen-doped graphene as enhanced materials in fabricating
      sensors for chemical and biochemical analysis.

PMID- 24287417
TI  - On-chip magneto-immunoassay for Alzheimer's biomarker electrochemical detection
      by using quantum dots as labels.
AB  - Electrochemical detection of cadmium-selenide/zinc-sulfide (CdSe@ZnS) quantum
      dots (QDs) as labeling carriers in an assay for apolipoprotein E (ApoE) detection
      has been evaluated. The immunocomplex was performed by using tosylactivated
      magnetic beads as preconcentration platform into a flexible hybrid
      polydimethylsiloxane (PDMS)-polycarbonate (PC) microfluidic chip with integrated
      screen printed electrodes (SPE). All the immunoassay was performed in chip and in
      flow mode. The sensitive electrochemical detection was obtained by square wave
      anodic stripping voltammetry. ApoE was evaluated for its potential as biomarker
      for Alzheimer's disease detection, achieving a limit of detection (LOD) of ~12.5
      ng mL(-1) with a linear range from 10 to 200 ng mL(-1) and high accuracy for
      diluted human plasma.

PMID- 24287418
TI  - Carbon nanotube signal amplification for ultrasensitive fluorescence polarization
      detection of DNA methyltransferase activity and inhibition.
AB  - A versatile sensing platform based on multiwalled carbon nanotube (MWCNT) signal
      amplification and fluorescence polarization (FP) is developed for the simple and
      ultrasensitive monitoring of DNA methyltransferase (MTase) activity and
      inhibition in homogeneous solution. This method uses a dye-labeled DNA probe that
      possess a doubled-stranded DNA (dsDNA) part for Mtase and its corresponding
      restriction endonuclease recognition, and a single-stranded DNA part for binding
      MWCNTs. In the absence of MTase, the dye-labeled DNA is cleaved by restriction
      endonuclease, and releases very short DNA carrying the dye that cannot bind to
      MWCNTs, which has relatively small FP value. However, in the presence of MTase,
      the specific recognition sequence in the dye-labeled DNA probe is methylated and
      not cleaved by restriction endonuclease. Thus, the dye-labeled methylated DNA
      product is adsorbed onto MWCNTs via strong pi-pi stacking interactions, which
      leads to a significant increase in the FP value due to the enlargement of the
      molecular volume of the dye-labeled methylated DNA/MWCNTs complex. This provides
      the basic of a quantitative measurement of MTase activity. By using the MWCNT
      signal amplification approach, the detection sensitivity can be significantly
      improved by two orders of magnitude over the previously reported methods.
      Moreover, this method also has high specificity and a wide dynamic range of over
      five orders of magnitude. Additionally, the suitability of this sensing platform
      for MTase inhibitor screening has also been demonstrated. This approach may serve
      as a general detection platform for sensitive assay of a variety of DNA MTases
      and screening potential drugs. 

PMID- 24287419
TI  - Flexible and transparent gastric battery: energy harvesting from gastric acid for
      endoscopy application.
AB  - In this paper, we present the potential to harvest energy directly from the
      digestive system for powering a future wireless endoscopy capsule. A
      microfabricated electrochemical cell on flexible parylene film is proposed as a
      gastric battery. This electrochemical cell uses gastric juice as a source of
      unlimited electrolyte. Planar fabricated zinc [Zn] and palladium [Pd] electrodes
      serve as anode and cathode respectively. Due to planar geometry, no separator is
      needed. Moreover the annular structure of the electrodes provides lower distance
      between cathode and anode reducing the internal resistance. Both electrodes are
      biocompatible and parylene provides flexibility to the system. For a surface area
      of 15 mm(2), 1.25 mW is generated which is sufficient for most implantable
      endoscopy applications. Open circuit output voltage of this battery is 0.75 V.
      Since this gastric battery does not require any external electrolyte, it has low
      intrinsic weight, and since it is flexible and is made of biocompatible
      materials, it offers a promising solution for power in implantable applications.

PMID- 24287420
TI  - Single layer linear array of microbeads for multiplexed analysis of DNA and
      proteins.
AB  - In this study, a microfluidic platform was developed to generate single layer,
      linear array of microbeads for multiplexed high-throughput analysis of
      biomolecules. The microfluidic device is comprised of eight microbead-trapping
      units, where microbeads were immobilized in a linear array format by the exertion
      of a negative pressure in the control channel connected to each sieving
      microstructure. Multiplexed assays were achieved by using a mixture of different
      spectrally-encoded microbeads functionalized with specific probes, followed by on
      chip reaction and detection. The microfluidic-based microbeads array platform was
      employed for multiplexed analysis of DNA and proteins, as demonstrated by the
      simultaneous discrimination of four HPV genotypes and the parallel detection of
      six different proteins. Compared with the off-chip protocols, the on-chip
      analysis exhibited better reaction efficiency, higher sensitivity and wider
      linear detection range. Visual inspection and identification of functionalized
      microbeads were facilitated by the single layer arrangement of microbeads so that
      accurate data acquisition can be performed during the detection process. 

PMID- 24287421
TI  - Identification and elimination of target-related matrix interference in a
      neutralizing anti-drug antibody assay.
AB  - Biopharmaceuticals administered to the human body have the potential to trigger
      the production of anti-drug (also called anti-therapeutic) antibodies (ADA) that
      can neutralize the therapeutic activity. For antibody therapeutics, cell-based
      neutralizing ADA assays are frequently used to evaluate ADA in clinical studies.
      We developed a method to detect neutralizing antibodies against MEDI-575, a fully
      human IgG2kappa antagonistic antibody against PDGFR-alpha. We evaluated three
      assay formats, two of which measured late responses, cell proliferation and
      apoptosis, whereas the third assay detected an early signaling event,
      phosphorylation of PDGFR-alpha. Measuring phosphorylation provided a superior
      assay window and therefore was developed as a neutralizing ADA (NAb) assay.
      Matrix interference, however, was significant, and could be identified to be
      caused by PDGF-AA and PDGF-AB, apparently the two most abundant ligands of PDGFR
      alpha present in human serum samples. A simple pre-treatment step, addition of an
      inhibitory antibody to PDGF-A, a subunit present in PDGF-AA and PDGF-AB, was
      found to eliminate matrix interference, increasing assay reliability and
      sensitivity. We integrated the pre-treatment step into assay development and
      qualified a robust NAb assay. 

PMID- 24287422
TI  - Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement
      cascade activation in vitro using an activated complement serum calibration
      standard.
AB  - Electroluminescent assays for epitopes on the complement components C3dg,
      terminal complement complex (TCC) and factor B/Bb (fB/Bb) have been developed
      with capture and detection antibodies to produce detection limits C3dg=91+/
      9ng/mL, TCC=3+/-0.1ng/mL and fB=55.7+/-0.1ng/mL. The assay performance was
      assessed against a series of zymosan and heat aggregated IgG (HAIgG) in vitro
      activations of complement using a calibrated activated complement serum (ACS) as
      calibration standard. The ACS standard was stable within 20% accuracy over a 6
      month period with freeze-thaw cycles as required. Differential activation of the
      complement cascade was observed for TCC showing a pseudo-first order formation
      half-life of 3.5h after activation with zymosan. The C3dg activation fragment
      indicates a 10% total activation for both activation agents. The kinetic-epitope
      analysis for fB indicates that the capture epitope is on the fB/Bb protein
      fragment which can then become covered by the formation of C3bBb or C3bBbP
      complexes during the time course of the cascade. 

PMID- 24287423
TI  - Non-specific binding in solid phase immunoassays for autoantibodies correlates
      with inflammation markers.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a validated and sensitive method for
      detection of human autoantibodies, but may have problems with specificity. Non
      specific binding is a well-known problem often observed in tests for
      autoantibodies, when sera are incubated on plastic surfaces, e.g. an ELISA plate.
      To understand the mechanisms underlying non-specific immunoglobulin deposition,
      we here analyse the phenomenon in detail and we propose means of reducing false
      positive test results caused by non-specific binding. The level of non-specific
      binding, in sera with suspected autoreactivity, was analysed in non-coated and
      autoantigen-coated ELISA wells and 4-32% of sera showed a high level of non
      specific binding depending on the assay conditions and serum properties. Non
      specifically binding sera were found to contain increased concentrations of IgG
      and other inflammatory mediators. Moreover, non-specific binding could be induced
      in serum by increasing the concentration of IgG and incubating the serum at 40 
      degrees C. This suggests that non-specific binding immunoglobulins can be formed
      during inflammation with high immunoglobulin levels and elevated temperature. We
      show that the level of non-specific binding correlates with the IgG concentration
      and therefore propose that non-specific binding may be interpreted as an
      informative finding indicative of elevated IgG and inflammation.

PMID- 24287424
TI  - Protein expression profiling by antibody array analysis with use of dried blood
      spot samples on filter paper.
AB  - Dried blood spot samples (DBSS) on filter paper offer several advantages compared
      to conventional serum/plasma samples: they do not require any phlebotomy or
      separation of blood by centrifugation; they are less invasive; they allow sample
      stability and shipment at room temperature; and they pose a negligible risk of
      infection with blood-borne viruses, such as HIV, HBV and HCV, to those who handle
      them. Therefore dried blood spot samples (DBSS) on filter paper can be a quick,
      convenient and inexpensive means of obtaining blood samples for biomarker
      discovery, disease screening, diagnosis and treatment monitoring in non
      hospitalized, public health settings. In this study, we investigated for the
      first time the potential application of dried blood spot samples (DBSS) in
      protein expression profiling using antibody array technology. First, optimal
      conditions for array assay performance using dried blood spot samples (DBSS) was
      established, including sample elution buffer, elution time, elution temperature
      and assay blocking buffer. Second, we analyzed dried blood spot samples (DBSS)
      using three distinct antibody array platforms, including sandwich-based antibody
      arrays, quantitative antibody arrays and biotin-label-based antibody arrays. In
      comparison with paired serum samples, detection of circulating proteins in dried
      blood spot samples (DBSS) correlated well for both low- and high-abundance
      proteins on all three antibody array platforms. In conclusion, our study strongly
      indicates the novel application of multiplex antibody array platforms to analyze
      dried blood spot samples (DBSS) on filter paper represents a viable, cost
      effective method for protein profiling, biomarker discovery and disease screening
      in a large, population-based survey. 

PMID- 24287425
TI  - Considerations for estimating daily intake values of nonpersistent environmental
      endocrine disruptors based on urinary biomonitoring data.
AB  - Human exposure to chemicals may be estimated by back-calculating urinary
      concentrations resulting from biomonitoring studies if knowledge of the
      chemical's toxicokinetic properties is available. In this paper, available
      toxicokinetic data for back-calculating urinary concentrations into daily intake
      values for bisphenol A (BPA), phthalates, parabens, and triclosan (TCS) are
      reviewed and knowledge gaps are identified. Human data is evaluated and presented
      with relevant animal data. Focus is on the recovery of the administered dose, the
      route of administration, and differences between humans and animals. Two human
      toxicokinetic studies are currently used to conclude that an oral dose of BPA is
      recoverable in urine and that no free BPA is present in plasma in spite of
      several contradicting biominotoring studies. Urinary recovery of an oral dose of
      phthalates in humans is complicated to assess due to extensive metabolism. In
      animals using (14)C-marked phthalates, near-complete recovery is observed. An
      oral dose of (14)C-marked parabens is also almost completely recovered in
      animals. In both humans and animals, however, two unspecific metabolites are
      formed, which complicates the back-calculation of parabens in humans. The
      recovery of both oral and dermal TCS in humans has been studied, but due to
      background levels of TCS, the back-calculation is difficult to perform. In
      conclusion, due to limited data, reasonable estimates of daily intake values
      based on urinary data are often not possible to obtain. Several knowledge gaps
      are identified and new studies are suggested. The route of administration used in
      toxicokinetic studies often does not match realistic scenarios. 

PMID- 24287426
TI  - Late-life effects on rat reproductive system after developmental exposure to
      mixtures of endocrine disrupters.
AB  - This study examined late-life effects of perinatal exposure of rats to a mixture
      of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats
      were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti
      androgenic and estrogenic chemicals including phthalates, pesticides, u.v.
      filters, bisphenol A, parabens, and the drug paracetamol. The groups received
      vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or
      450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine
      predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous
      cyclicity at 9 and 12 months of age were assessed. Few female offspring showed
      significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and
      AAMix450 groups compared with controls. In 19-month-old male offspring,
      epididymal sperm counts were lower than controls, and in ventral prostate an
      overrepresentation of findings related to hyperplasia was observed in exposed
      groups compared with controls, particularly in the group dosed with anti
      androgens. A higher incidence of pituitary adenoma at 19 months of age was found
      in males and females in the AAMix450 group. Developmental exposure of rats to the
      highest dose of a human-relevant mixture of endocrine disrupters induced adverse
      effects late in life, manifested as earlier female reproductive senescence,
      reduced sperm counts, higher score for prostate atypical hyperplasia, and higher
      incidence of pituitary tumors. These delayed effects highlight the need for
      further studies on the role of endocrine disrupters in hormone-related disorders
      in aging humans. 

PMID- 24287427
TI  - Hemodynamic sensor in cardiac implantable electric devices: the endocardial
      accelaration technology.
AB  - There have been substantial progresses in the technology of cardiac implantable
      electric devices (CIEDs) during the past decades. One of the progresses is
      represented by the development of a hemodynamic sensor embedded at the tip of a
      pacing lead that measures myocardial contractility by the analysis of myocardial
      mechanical vibrations occurring during the cardiac cycle. This sensor, providing
      continuous hemodynamic monitoring, could play an important role in clinical
      practice because of several clinical applications in CIEDs recipients. The
      objectives of this work are to report how this sensor operates and to review the
      main findings about its clinical applications. 

PMID- 24287428
TI  - Electrocardiogram pattern recognition and analysis based on artificial neural
      networks and support vector machines: a review.
AB  - Computer systems for Electrocardiogram (ECG) analysis support the clinician in
      tedious tasks (e.g., Holter ECG monitored in Intensive Care Units) or in prompt
      detection of dangerous events (e.g., ventricular fibrillation). Together with
      clinical applications (arrhythmia detection and heart rate variability analysis),
      ECG is currently being investigated in biometrics (human identification), an
      emerging area receiving increasing attention. Methodologies for clinical
      applications can have both differences and similarities with respect to
      biometrics. This paper reviews methods of ECG processing from a pattern
      recognition perspective. In particular, we focus on features commonly used for
      heartbeat classification. Considering the vast literature in the field and the
      limited space of this review, we dedicated a detailed discussion only to a few
      classifiers (Artificial Neural Networks and Support Vector Machines) because of
      their popularity; however, other techniques such as Hidden Markov Models and
      Kalman Filtering will be also mentioned. 

PMID- 24287429
TI  - Opto-physiological modeling applied to photoplethysmographic cardiovascular
      assessment.
AB  - This paper presents opto-physiological (OP) modeling and its application in
      cardiovascular assessment techniques based on photoplethysmography (PPG).
      Existing contact point measurement techniques, i.e., pulse oximetry probes, are
      compared with the next generation non-contact and imaging implementations, i.e.,
      non-contact reflection and camera-based PPG. The further development of effective
      physiological monitoring techniques relies on novel approaches to OP modeling
      that can better inform the design and development of sensing hardware and
      applicable signal processing procedures. With the help of finite-element optical
      simulation, fundamental research into OP modeling of photoplethysmography is
      being exploited towards the development of engineering solutions for practical
      biomedical systems. This paper reviews a body of research comprising two OP
      models that have led to significant progress in the design of transmission mode
      pulse oximetry probes, and approaches to 3D blood perfusion mapping for the
      interpretation of cardiovascular performance. 

PMID- 24287430
TI  - Evaluation of postprandial glucose excursion using a novel minimally invasive
      glucose area-under-the-curve monitoring system.
AB  - OBJECTIVE: To develop a minimally invasive interstitial fluid extraction
      technology (MIET) to monitor postprandial glucose area under the curve (AUC)
      without blood sampling, we evaluated the accuracy of glucose AUC measured by MIET
      and compared with that by blood sampling after food intake. METHODS: Interstitial
      fluid glucose AUC (IG-AUC) following consumption of 6 different types of foods
      was measured by MIET. MIET consisted of stamping microneedle arrays, placing
      hydrogel patches on the areas, and calculating IG-AUC based on glucose levels in
      the hydrogels. Glycemic index (GI) was determined using IG-AUC and reference AUC
      measured by blood sampling. RESULTS: IG-AUC strongly correlated with reference
      AUC (R = 0.91), and GI determined using IG-AUC showed good correlation with that
      determined by reference AUC (R = 0.88). CONCLUSIONS: IG-AUC obtained by MIET can
      accurately predict the postprandial glucose excursion without blood sampling. In
      addition, feasibility of GI measurement by MIET was confirmed.

PMID- 24287431
TI  - Modelling of thermal hyperemia in the skin of type 2 diabetic patients.
AB  - The microcirculatory response to thermal stimulation involves both an axon reflex
      and NO-mediated activation. The analysis of the microcirculatory flow following
      thermal stimulation may therefore enhance the detection of any impairment of the
      small unmyelinated fibres that are involved in the axon reflex. The aim of this
      work is to establish a method of non-invasive measurement of small fibre
      impairment. The microcirculatory flow in response to local heating is measured by
      using a laser Doppler instrument, and mathematically modelled to extract a set of
      quantitative parameters. The results confirm that there is a significant
      difference in the parameters modelling the axon reflex between diabetic and
      control subjects, while no significant difference is found in the parameters
      modelling the NO-mediated activation. 

PMID- 24287432
TI  - Measurement of lower limb joint kinematics using inertial sensors during stair
      ascent and descent in healthy older adults and stroke survivors.
AB  - This study validated the feasibility of inertial sensors in estimating lower limb
      joint kinematics during stair ambulation in healthy older adults and stroke
      survivors. Three dimensional motion data were collected using an inertial sensor
      based system from 9 persons with stroke and 9 healthy older adults as they
      ascended and descended a staircase at a self-selected pace. The measured joint
      angles were compared with a laboratory-based motion capture system by computing
      differences in range of motion (RoM), grand mean error, standard deviation, and
      coefficients of multiple correlations. For stroke survivors, differences in RoM
      measurements between these two systems were determined to be 3.3 +/- 8.1 degrees
      , while the highest correlations were found in the estimation of sagittal plane
      joint angles after offset correction. Results suggest that the inertial sensor
      system is suitable for estimating major joint angles in healthy older adults as
      well as the RoM for stroke survivors. New calibration procedures are necessary
      for applying the technology to a stroke population. 

PMID- 24287433
TI  - A preliminary study on the characterization of follicular helper T (Tfh) cells in
      rheumatoid arthritis synovium.
AB  - Rheumatoid arthritis (RA) is a chronic and systematic autoimmune inflammatory
      disease. Recently, a novel T cell subset, follicular helper CD4 T cell (Tfh
      cells) was found in relation to the pathogenesis and progression of RA, and
      increased numbers of circulating Tfh cells were found in RA patients. However,
      there is little evidence regarding the localization of Tfh cells in synovium
      tissues from RA patients, owing to the lack of an available method to
      characterize their localization in tissue. The aim of our present study was to
      characterize the Tfh cells in rheumatoid synovium tissues from RA patients by
      using immunohistochemistry and triple-fluorescence immunostaining methods. Our
      results showed that specific staining of CD4, CXCR5 and ICOS could be found on
      infiltrating immune cells in rheumatoid synovium tissues. The use of triple
      fluorescence immunostaining and confocal laser scanning showed immunolocalization
      of CD4(+)CXCR5(+)ICOS(+)T cells (Tfh cells) in the rheumatoid synovium tissues,
      whereas these signals were absent in osteoarthritis (OA) synovium and in normal
      synovium tissues. Thus the data from our present preliminary study support the
      notion that CD4(+)CXCR5(+)ICOS(+)Tfh cells could be found in rheumatoid synovium
      tissues from RA patients, indicating the possibility that this T cell subset in
      synovium tissues may have important roles in the pathogenesis and progression of
      RA. 

PMID- 24287434
TI  - Inherited susceptibility to pre B-ALL caused by germline transmission of PAX5
      c.547G>A.

PMID- 24287435
TI  - Biomarker-guided translation of brain imaging into disease pathway models.
AB  - The advent of state-of-the-art brain imaging technologies in recent years and the
      ability of such technologies to provide high-resolution information at both
      structural and functional levels has spawned large efforts to introduce novel non
      invasive imaging biomarkers for early prediction and diagnosis of brain
      disorders; however, their utility in both clinic and drug development at their
      best resolution remains limited to visualizing and monitoring disease
      progression. Given the fact that efficient translation of valuable information
      embedded in brain scans into clinical application is of paramount scientific and
      public health importance, a strategy is needed to bridge the current gap between
      imaging and molecular biology, particularly in neurodegenerative diseases. As an
      attempt to address this issue, we present a novel computational method to link
      readouts of imaging biomarkers to their underlying molecular pathways with the
      aim of guiding clinical diagnosis, prognosis and even target identification in
      drug discovery for Alzheimer's disease. 

PMID- 24287436
TI  - Using eye movements to investigate selective attention in chronic daily headache.
AB  - Previous research has demonstrated that chronic pain is associated with biased
      processing of pain-related information. Most studies have examined this bias by
      measuring response latencies. The present study extended previous work by
      recording eye movement behaviour in individuals with chronic headache and in
      healthy controls while participants viewed a set of images (i.e., facial
      expressions) from 4 emotion categories (pain, angry, happy, neutral). Biases in
      initial orienting were assessed from the location of the initial shift in gaze,
      and biases in the maintenance of attention were assessed from the duration of
      gaze on the picture that was initially fixated, and the mean number of visits,
      and mean fixation duration per image category. The eye movement behaviour of the
      participants in the chronic headache group was characterised by a bias in initial
      shift of orienting to pain. There was no evidence of individuals with chronic
      headache visiting more often, or spending significantly more time viewing, pain
      images compared to other images. Both participant groups showed a significantly
      greater bias to maintain gaze longer on happy images, relative to pain, angry,
      and neutral images. Results are consistent with a pain-related bias that operates
      in the orienting of attention on pain-related stimuli, and suggest that chronic
      pain participants' attentional biases for pain-related information are evident
      even when other emotional stimuli are present. Pain-related information
      processing biases appear to be a robust feature of chronic pain and may have an
      important role in the maintenance of the disorder.

PMID- 24287437
TI  - Mechanisms of cortical plasticity in migraine patients.

PMID- 24287439
TI  - Parietal structure and function explain human variation in working memory biases
      of visual attention.
AB  - Recent research indicates that human attention appears inadvertently biased by
      items that match the contents of working memory (WM). WM-biases can lead to
      attentional costs when the memory content matches goal-irrelevant items and to
      attentional benefits when it matches the sought target. Here we used functional
      and structural MRI data to determine the neural basis of human variation in WM
      biases. We asked whether human variation in WM-benefits and WM-costs merely
      reflects the process of attentional capture by the contents of WM or whether
      variation in WM biases may be associated with distinct forms of cognitive control
      over internal WM signals based on selection goals. Human ability to use WM
      contents to facilitate selection was positively correlated with gray matter
      volume in the left superior posterior parietal cortex (PPC), while the ability to
      overcome interference by WM-matching distracters was associated with the left
      inferior PPC in the anterior IPS. Functional activity in the left PPC, measured
      by functional MRI, also predicted the magnitude of WM-costs on selection. Both
      structure and function of left PPC mediate the expression of WM biases in human
      visual attention. 

PMID- 24287438
TI  - Connectivity trajectory across lifespan differentiates the precuneus from the
      default network.
AB  - The default network of the human brain has drawn much attention due to its
      relevance to various brain disorders, cognition, and behavior. However, its
      functional components and boundaries have not been precisely defined. There is no
      consensus as to whether the precuneus, a hub in the functional connectome, acts
      as part of the default network. This discrepancy is more critical for brain
      development and aging studies: it is not clear whether age has a stronger impact
      on the default network or precuneus, or both. We used Generalized Ranking and
      Averaging Independent Component Analysis by Reproducibility (gRAICAR) to
      investigate the lifespan trajectories of intrinsic functional networks. By
      estimating individual-specific spatial components and aligning them across
      subjects, gRAICAR measures the spatial variation of component maps across a
      population without constraining the same components to appear in every subject.
      In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age
      dependence in the spatial pattern of a precuneus-dorsal posterior cingulate
      cortex network compared to the default network, despite the fact that the two
      networks exhibit considerable spatial overlap and temporal correlation. These
      results remained even when analyses were restricted to a subpopulation with very
      similar head motion across age. Our analyses further showed that the two networks
      tend to merge with increasing age. Post-hoc analyses of functional connectivity
      confirmed the distinguishable cross-lifespan trajectories between the two
      networks. Based on these observations, we proposed a dynamic model of cross
      lifespan functional segregation and integration between the two networks,
      suggesting that the precuneus network may have a different functional role than
      the default network, which declines with age. These findings have implications
      for understanding the functional roles of the default network, gaining insight
      into its dynamics throughout life, and guiding interpretation of alterations in
      brain disorders. 

PMID- 24287440
TI  - Polarity-specific effects of motor transcranial direct current stimulation on
      fMRI resting state networks.
AB  - Transcranial direct current stimulation (tDCS) has been used to modify motor
      performance in healthy and patient populations. However, our understanding of the
      large-scale neuroplastic changes that support such behavioural effects is
      limited. Here, we used both seed-based and independent component analyses (ICA)
      approaches to probe tDCS-induced modifications in resting state activity with the
      aim of establishing the effects of tDCS applied to the primary motor cortex (M1)
      on both motor and non-motor networks within the brain. Subjects participated in
      three separate sessions, during which resting fMRI scans were acquired before and
      after 10min of 1mA anodal, cathodal, or sham tDCS. Cathodal tDCS increased the
      inter-hemispheric coherence of resting fMRI signal between the left and right
      supplementary motor area (SMA), and between the left and right hand areas of M1.
      A similar trend was documented for the premotor cortex (PMC). Increased
      functional connectivity following cathodal tDCS was apparent within the ICA
      generated motor and default mode networks. Additionally, the overall strength of
      the default mode network was increased. Neither anodal nor sham tDCS produced
      significant changes in resting state connectivity. This work indicates that
      cathodal tDCS to M1 affects the motor network at rest. In addition, the effects
      of cathodal tDCS on the default mode network support the hypothesis that
      diminished top-down control may contribute to the impaired motor performance
      induced by cathodal tDCS.

PMID- 24287441
TI  - Weighing the stigma of weight: An fMRI study of neural reactivity to the pain of
      obese individuals.
AB  - Explicit negative attitudes and blameful beliefs (e.g. poor diet, laziness)
      towards obese individuals are well documented and are pervasive even among health
      professionals. Here we sought to determine whether obesity stigma is reflected in
      a fundamental feature of intersubjectivity namely the automatic neural resonance
      with others' affective experiences. During fMRI, normal-weight female
      participants observed short clips depicting normal-weight (NW) and obese (Ob)
      models experiencing pain. Importantly, participants believed that half of the Ob
      were overweight due to a hormonal disorder (HormOb) and ignored the cause of
      obesity of the remaining models (Unknown obese models; UnkOb). Analyses of
      hemodynamic responses showed reduced activity to the pain of Ob compared to that
      of NW in areas associated with pain processing and early visual processing. The
      comparison between the two Ob conditions revealed a further decrease of activity
      to HormOb's pain compared to UnkOb's (and NW) pain in the right inferior frontal
      gyrus, an area associated with emotional resonance. Our study demonstrates that
      stigma for obese individuals can be observed at implicit levels, and that it is
      modulated by knowledge concerning the etiology of obesity, with the seemingly
      surprising result that obesity due to disease may result in greater
      stigmatization. Moreover, the perceived similarity with the models and the
      ambivalent emotion of pity may index biased brain responses to obese individuals'
      pain. The study highlights a possibly important neural link between resonance
      with the pain of others and obesity stigma. 

PMID- 24287442
TI  - Visuospatial bootstrapping: implicit binding of verbal working memory to
      visuospatial representations in children and adults.
AB  - When participants carry out visually presented digit serial recall, their
      performance is better if they are given the opportunity to encode extra
      visuospatial information at encoding-a phenomenon that has been termed
      visuospatial bootstrapping. This bootstrapping is the result of integration of
      information from different modality-specific short-term memory systems and
      visuospatial knowledge in long term memory, and it can be understood in the
      context of recent models of working memory that address multimodal binding (e.g.,
      models incorporating an episodic buffer). Here we report a cross-sectional
      developmental study that demonstrated visuospatial bootstrapping in adults (n=18)
      and 9-year-old children (n=15) but not in 6-year-old children (n=18). This is the
      first developmental study addressing visuospatial bootstrapping, and results
      demonstrate that the developmental trajectory of bootstrapping is different from
      that of basic verbal and visuospatial working memory. This pattern suggests that
      bootstrapping (and hence integrative functions such as those associated with the
      episodic buffer) emerge independent of the development of basic working memory
      slave systems during childhood. 

PMID- 24287447
TI  - Assessment of inhibitory potential of Pothos scandens L. on ovalbumin-induced
      airway hyperresponsiveness in balb/c mice.
AB  - Pothos scandens L. was used in Indian traditional medicine as an antiasthmatic
      drug. The ethanolic and aqueous extracts were prepared with aerial parts of P.
      scandens (PSE & PSA). ESI MS/MS of PSE ethanolic extract was carried out for the
      determination of chemical constituents. CP1 is isolated from the PSE,
      structurally confirmed with NMR and LCMS/MS. PSE, PSA and CP1 are evaluated
      against ovalbumin (OVA) induced airway hyperresponsiveness (AHR) in balb/c mice.
      The test drugs are administered p.o. prior to challenge with aerosolized 2.5% w/v
      OVA. Total and differential leucocyte count, nitrite (NO2), nitrate (NO3), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-13 (IL
      13) are estimated in bronchoalveolar lavage fluid (BALF). Similarly,
      myeloperoxidase (MPO), malonaldehyde (MDA) and total lung protein (TLP) are
      estimated in the lungs. The results reveal a significant increase in total and
      differential leucocyte count, NO2, NO3, TNF-alpha, IL-6, and IL-13 in OVA induced
      AHR. However, these parameters are significantly decreased in PSE and PSA tested
      doses (PSE 100 & 200mg/kg). While, treatment with CP1 is less effective at 5 &
      10mg/kg doses. Similar observations obtain for MPO and MDA in lungs. However, the
      mean value indicated that the PSE at 200mg/kg showed a significant restoration in
      all the parameters. Pro-inflammatory mediators are known to be responsible for
      AHR. Histopathology revealed justifies the effectiveness. The present
      investigations suggest PSE are interesting molecules for further research for
      asthma, with an approach through pro-inflammatory inhibitory pathway. P. scandens
      is a potential herbal medicine for allergy induced asthma. 

PMID- 24287448
TI  - Effects of opioid therapy on human natural killer cells.
AB  - Opioid compounds, such as morphine, induce powerful analgesic effects and are
      extensively used clinically to treat a wide variety of pain. The aim of our study
      was to evaluate the impact of opioid therapy on phenotype and function peripheral
      blood NK cells. The patients were referred to three Italian pain therapy centers
      (Milan, Pavia, Piacenza) for chronic pain in neuropathic or mixed somatic
      components. The patients were between 18 and 75 years old and were of Caucasian
      ethnicity. We studied the expression of activating and inhibitory NK receptors to
      discriminate NK subsets with different CD56 surface expression intensities
      (CD56(bright) and CD56(dull) NK cells). The flow cytometry analysis of the NK
      cells was at normal levels in peripheral blood lymphocytes with fewer
      CD56(bright) compared to the CD56(dull) NK cell subset when compared to blood
      from drug free donors. Furthermore, the cytolytic activity of in vitro patient NK
      cells analyzed was not lower, as would be expected from the regular expression of
      activating NK receptors for both subsets. Taken together, these data indicate
      that NK cells from opioid treated patients do not show any signs of NK cell
      immune-suppression.

PMID- 24287449
TI  - A combination of sinomenine and methotrexate reduces joint damage of collagen
      induced arthritis in rats by modulating osteoclast-related cytokines.
AB  - OBJECTIVE: To analyze the combination therapy of Sinomenine (SIN) and
      Methotrexate (MTX) in rheumatoid arthritis (RA), we herein demonstrated the
      combination effect of SIN and MTX on collagen-induced arthritis (CIA) in rats
      through their modulation on osteoclast-related cytokines. METHODS: CIA was
      induced by the immunization of type II collagen (CII) in SD rats. SIN and MTX
      were administrated alone or in combination after the onset of arthritis.
      Arthritis index and histological analysis were used to evaluate the effect of
      treatments. Effects of SIN and MTX on expression of receptor activator of NF
      kappaB ligand (RANKL) and osteopontin (OPN) in synovial tissues were assayed by
      immunohistochemistry. RANKL, osteoprotegerin (OPG), IL-6, IL-17 and matrix
      metalloproteinases (MMPs) in rat serum were measured by ELISA. The expression of
      osteoclast-related cytokines in fibroblast-like synoviocytes (FLS) from RA
      patients was assayed by RT-PCR. RESULTS: SIN and MTX combination additively
      reduced the inflammatory symptoms and joint damage in CIA. Combination of SIN and
      MTX significantly repressed synovial RANKL and OPN production. SIN and MTX
      exhibited complementary and synergistic effect upon down-regulating RANKL, IL-6,
      IL-17 and MMPs in rat serum. SIN and MTX also modulated the expression of RANKL
      and OPG in RA-FLS. CONCLUSION: SIN and MTX have additive effects, decreasing
      inflammation and joint damage in CIA rats by modulating osteoclast-related
      cytokines. These results are indicative of the combined effect of SIN and MTX for
      anti-arthritic treatment in RA.

PMID- 24287450
TI  - Effects of suspended titanium dioxide nanoparticles on cake layer formation in
      submerged membrane bioreactor.
AB  - Effects of the suspended titanium dioxide nanoparticles (TiO2 NPs, 50 mg/L) on
      the cake layer formation in a submerged MBR were systematically investigated.
      With nanometer sizes, TiO2 NPs were found to aggravate membrane pore blocking but
      postpone cake layer fouling. TiO2 NPs showed obvious effects on the structure and
      the distribution of the organic and the inorganic compounds in cake layer.
      Concentrations of fatty acids and cholesterol in the cake layer increased due to
      the acute response of bacteria to the toxicity of TiO2 NPs. Line-analysis and dot
      map of energy-dispersive X-ray were also carried out. Since TiO2 NPs inhibited
      the interactions between the inorganic and the organic compounds, the inorganic
      compounds (especially SiO2) were prevented from depositing onto the membrane
      surface. Thus, the postponed cake layer fouling was due to the changing features
      of the complexes on the membrane surface caused by TiO2 NPs.

PMID- 24287451
TI  - Suitability of giant reed (Arundo donax L.) for anaerobic digestion: effect of
      harvest time and frequency on the biomethane yield potential.
AB  - This study aimed to investigate the potential of giant reed for biomethane
      production by examining the influence of harvest time and frequency on the
      Biochemical Methane Potential (BMP), the kinetics of biomethane accumulation in
      batch reactors and the expected methane yield per hectare. The crop was cut at
      five different times, regrowths from early cuts were harvested in autumn and BMP
      of each cut was assessed. The highest BMP (392 NL kg VS(-1)) and the best
      kinetics of methane production were associated to juvenile traits of the crop. By
      coupling the early cuts with the corresponding regrowths (double harvest), the
      dry biomass (from 35 to 40 Mg ha(-1)) equaled that obtained by a single cut at
      end of the season (38 Mg ha(-1)), while the methane yield per hectare (11,585
      12,981 Nm(3) ha(-1)) exceeded up to 35% the methane produced with a single
      harvest at crop maturity (9452 Nm(3) ha(-1)).

PMID- 24287452
TI  - Hydrothermal liquefaction of mixed-culture algal biomass from wastewater
      treatment system into bio-crude oil.
AB  - In this study, a mixed-culture algal biomass harvested from a functioning
      wastewater treatment system (AW) was hydrothermally converted into bio-crude
      oils. The highest bio-crude oil yield (49% of volatile matter) and the highest
      energy recovery were obtained at 300  degrees C with 1 h retention time. The
      highest heating value of the bio-crude oil was 33.3 MJ/kg, produced at 320 
      degrees C and 1h retention time. Thermogravimetric analysis showed approximately
      60% of the bio-crude oils were distilled in the range of 200-550  degrees C; and
      the solid residue might be suitable for use in asphalt. GC-MS results indicated
      that the bio-crude oil contained hydrocarbons and fatty acids, while the aqueous
      product was rich in organic acids and cyclic amines. The nitrogen recovery (NR)
      in the bio-crude oil ranged from 8.41% to 16.8%, which was lower than the typical
      range of 25%-53% from previous studies.

PMID- 24287453
TI  - Antennal pointing at a looming object in the cricket Acheta domesticus.
AB  - Antennal pointing responses to approaching objects were observed in the house
      cricket Acheta domesticus. In response to a ball approaching from the lateral
      side, crickets oriented the antenna ipsilateral to the ball towards it. In
      response to a ball approaching from the front, crickets oriented both antennae
      forward. Response rates of antennal pointing were higher when the ball was
      approaching from the front than from behind. The antennal angle ipsilateral to
      the approaching ball was positively correlated with approaching angle of the
      ball. Obstructing the cricket's sight decreased the response rate of antennal
      pointing, suggesting that this response was elicited mainly by visual stimuli.
      Although the response rates of antennal pointing decreased when the object ceased
      its approach at a great distance from the cricket, antennal pointing appeared to
      be resistant to habituation and was not substantially affected by the velocity,
      size and trajectory of an approaching ball. When presented with computer
      generated visual stimuli, crickets frequently showed the antennal pointing
      response to a darkening stimulus as well as looming and linearly-expanding
      stimuli. Drifting gratings rarely elicited the antennal pointing. These results
      suggest that luminance change is sufficient to elicit antennal pointing. 

PMID- 24287454
TI  - ALIX and the multivesicular endosome: ALIX in Wonderland.
AB  - In yeast and mammalian cells, endosomal sorting complexes required for transport
      (ESCRT) assist in sorting ubiquitinated proteins into intralumenal vesicles
      (ILVs) of multivesicular endosomes (MVEs) for degradation in the
      lysosome/vacuole. In mammalian cells, ESCRTs also drive other topologically
      identical membrane deformation processes, including cytokinesis, exosome release,
      and virus budding. Although the ESCRT-associated protein ALIX regulates these
      mammalian cell-specific functions, it was believed to be dispensable for receptor
      sorting into ILVs, unlike its yeast homolog Bro1. Despite these differences,
      recent evidence suggests ALIX and Bro1 share common properties in cargo sorting
      and ILV formation. We review these commonalities and discuss the role of ALIX in
      operating 'behind the mirror' during ILV back-fusion with the limiting membrane.
      We also propose models of how ALIX and some ESCRTs regulate the back-fusion
      process. 

PMID- 24287455
TI  - The role of social media in online weight management: systematic review.
AB  - BACKGROUND: Social media applications are promising adjuncts to online weight
      management interventions through facilitating education, engagement, and peer
      support. However, the precise impact of social media on weight management is
      unclear. OBJECTIVE: The objective of this study was to systematically describe
      the use and impact of social media in online weight management interventions.
      METHODS: PubMed, PsycINFO, EMBASE, Web of Science, and Scopus were searched for
      English-language studies published through March 25, 2013. Additional studies
      were identified by searching bibliographies of electronically retrieved articles.
      Randomized controlled trials of online weight management interventions that
      included a social media component for individuals of all ages were selected.
      Studies were evaluated using 2 systematic scales to assess risk of bias and study
      quality. RESULTS: Of 517 citations identified, 20 studies met eligibility
      criteria. All study participants were adults. Because the included studies varied
      greatly in study design and reported outcomes, meta-analysis of interventions was
      not attempted. Although message boards and chat rooms were the most common social
      media component included, their effect on weight outcomes was not reported in
      most studies. Only one study measured the isolated effect of social media. It
      found greater engagement of participants, but no difference in weight-related
      outcomes. In all, 65% of studies were of high quality; 15% of studies were at low
      risk of bias. CONCLUSIONS: Despite the widespread use of social media, few
      studies have quantified the effect of social media in online weight management
      interventions; thus, its impact is still unknown. Although social media may play
      a role in retaining and engaging participants, studies that are designed to
      measure its effect are needed to understand whether and how social media may
      meaningfully improve weight management.

PMID- 24287456
TI  - Clonal intratumor heterogeneity of promoter hypermethylation in breast cancer by
      MS-MLPA.
AB  - Intratumor heterogeneity may lead to sampling bias and may present major
      challenges to personalized medicine and biomarker development. Despite many
      studies investigating genetic heterogeneity, epigenetic intratumor heterogeneity
      of promoter hypermethylation has only rarely been examined in breast cancer. To
      examine clonal intratumor heterogeneity of promotor hypermethylation, we
      performed methylation-specific multiplex ligation-dependent probe amplification
      (MS-MLPA) for 24 established tumor-suppressor genes on multiple spatially
      separated samples obtained from 21 primary breast carcinomas. Multiregion
      analysis was performed, representing at least two and a maximum of five tumor
      blocks per patient and four areas per tumor block. Methylation results were
      heterogeneous at one or more genetic loci between different tumor regions in 95%
      of breast carcinomas. The most heterogeneous loci in decreasing frequency were
      RASSF1A (62%), CDKN2B (43%), APC (38%), GSTP1 (33%), CDH13 (24%), DAPK1 (19%),
      and CDKN1B (5%). Heterogeneity lead to a methylation status change in at least
      one locus in 65% of the tumors. For most genes, the relative contribution of
      between-patients and between-block variability to the total variation in
      methylation results was similar. Regardless of the gene, contribution of within
      block variability was of little importance. In conclusion, although most
      variation in methylation status is present between individual breast cancers,
      clonal epigenetic heterogeneity is seen within most primary breast carcinomas,
      indicating that methylation results from a single random sample may not be
      representative of the whole tumor. 

PMID- 24287457
TI  - Smooth muscle differentiation identifies two classes of poorly differentiated
      pleomorphic sarcomas with distinct outcome.
AB  - The clinical relevance of accurately diagnosing pleomorphic sarcomas has been
      shown, especially in cases of undifferentiated pleomorphic sarcomas with myogenic
      differentiation, which appear significantly more aggressive. To establish a new
      smooth muscle differentiation classification and to test its prognostic value,
      412 sarcomas with complex genetics were examined by immunohistochemistry using
      four smooth muscle markers (calponin, h-caldesmon, transgelin and smooth muscle
      actin). Two tumor categories were first defined: tumors with positivity for all
      four markers and tumors with no or incomplete phenotypes. Multivariate analysis
      demonstrated that this classification method exhibited the strongest prognostic
      value compared with other prognostic factors, including histological
      classification. Secondly, incomplete or absent smooth muscle phenotype tumor
      group was then divided into subgroups by summing for each tumor the labeling
      intensities of all four markers for each tumors. A subgroup of tumors with an
      incomplete but strong smooth muscle differentiation phenotype presenting an
      intermediate metastatic risk was thus identified. Collectively, our results show
      that the smooth muscle differentiation classification method may be a useful
      diagnostic tool as well as a relevant prognostic tool for undifferentiated
      pleomorphic sarcomas. 

PMID- 24287458
TI  - Differential microRNA expression profiles between malignant rhabdoid tumor and
      epithelioid sarcoma: miR193a-5p is suggested to downregulate SMARCB1 mRNA
      expression.
AB  - Malignant rhabdoid tumor and epithelioid sarcoma are classified as tumors of
      uncertain differentiation. However, it is controversial whether these tumors are
      distinct entities because they share similar histological and immunohistochemical
      features such as the existence of rhabdoid cells or complete loss of SMARCB1
      protein expression. MicroRNAs are small non-coding RNAs, and it is suggested that
      knowledge of microRNA expression profiles in cancer may have substantial value
      for diagnostics. We first analyzed microRNA expression profiles in 13 frozen
      materials (five malignant rhabdoid tumors, two proximal type epithelioid
      sarcomas, and six conventional type epithelioid sarcomas) and subsequently
      examined the specific microRNA expressions in 29 paraffin-embedded materials (8
      malignant rhabdoid tumors, 13 proximal type epithelioid sarcomas, and 8
      conventional type epithelioid sarcomas) and 13 previously described frozen
      materials by quantitative RT-PCR. According to the unsupervised hierarchical
      clustering of microRNA, proximal type epithelioid sarcoma and conventional type
      epithelioid sarcoma were classified into the same category, whereas malignant
      rhabdoid tumor was a distinct category from both types of epithelioid sarcoma. In
      addition, when malignant rhabdoid tumor with SMARCB1 gene alterations and
      proximal type and conventional type epithelioid sarcoma with no SMARCB1 gene
      alterations were compared, 56 microRNAs were isolated as being significantly
      different (ANOVA, P<0.05). Among them, quantitative RT-PCR using frozen and
      paraffin-embedded materials demonstrated that expression levels of miR193a-5p
      (P=0.002), which has been suggested to downregulate SMARCB1 mRNA expression,
      showed statistically different expression levels between malignant rhabdoid tumor
      and epithelioid sarcoma with no SMARCB1 gene alterations. These results suggest
      that epithelioid sarcoma, especially proximal type epithelioid sarcoma, and
      malignant rhabdoid tumor are distinct tumors with respect to the microRNA
      expression profiles and that miR193a-5p may have an important role in the
      inhibition of SMARCB1 mRNA expression. 

PMID- 24287459
TI  - Preparation and characterization of highly planar flexible silver crystal belts.
AB  - We report a novel simple one-pot strategy for fabricating pure and highly planar
      silver (Ag) crystal belts. Unique single-crystal Ag belts (high width-to
      thickness ratio ~50) were successfully synthesized in high yield (80 wt%) by
      reducing AgNO3 using N,N,N',N'-tetramethylethylenediamine (TEMED) as a reducing
      and a structure-determining agent in the presence of polyethylene glycol (PEG)
      under mild conditions.

PMID- 24287460
TI  - A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends
      (SMART) from 2002 to 2011.
AB  - Surveillance of antimicrobial agent resistance provides important information to
      guide microbiologists and infectious disease specialists understanding of the
      control and the spread of resistance mechanisms within the local environment.
      Continued monitoring of antimicrobial resistance patterns in the community and in
      local hospital environments is essential to guide effective empiric therapy. The
      Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored the in
      vitro susceptibility patterns of clinical Gram-negative bacilli to antimicrobial
      agents collected worldwide from intra-abdominal infections since 2002 and urinary
      tract infections since 2009. Resistance trends, with a particular focus on
      carbapenem resistance and the rate of extended-spectrum beta-lactamases (ESBLs),
      were analyzed. Isolates from intra-abdominal infections (n = 92,086) and urinary
      tract infections (n = 24,705) were collected and tested using Clinical and
      Laboratory Standards Institute methods. This review presents carbapenem
      susceptibility and ESBL rates over ten years of SMART study analysis, including
      key publications during this period. The SMART study has proved to be a valuable
      resource in determining pathogen prevalence and antibiotic susceptibility over
      the last ten years and continues to provide evidence for regulatory
      susceptibility breakpoints and clinical decision making. 

PMID- 24287461
TI  - Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2:
      Genetic Testing to Assess Gout Risk.
AB  - In mammals, excess purine nucleosides are removed from the body by breakdown in
      the liver and excretion from the kidneys. Uric acid is the end product of purine
      metabolism in humans. Two-thirds of uric acid in the human body is normally
      excreted through the kidney, whereas one-third undergoes uricolysis
      (decomposition of uric acid) in the gut. Elevated serum uric acid levels result
      in gout and could be a risk factor for cardiovascular disease and diabetes.
      Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays
      a role of renal excretion of uric acid. Two non-synonymous single nucleotide
      polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene
      result in impaired transport activity, owing to ubiquitination-mediated
      proteosomal degradation and truncation of ABCG2, respectively. These genetic
      polymorphisms are associated with hyperuricemia and gout. Allele frequencies of
      those SNPs are significantly higher in Asian populations than they are in African
      and Caucasian populations. A rapid and isothermal genotyping method has been
      developed to detect the SNP 421C>A, where one drop of peripheral blood is
      sufficient for the detection. Development of simple genotyping methods would
      serve to improve prevention and early therapeutic intervention for high-risk
      individuals in personalized healthcare. 

PMID- 24287463
TI  - Longitudinal Assessment of Antimicrobial Susceptibility among Gram-Negative and
      Gram-Positive Organisms Collected from Italy as Part of the Tigecycline
      Evaluation and Surveillance Trial between 2004 and 2011.
AB  - The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was initiated in
      2004 to longitudinally monitor the activity of the broad-spectrum glycylcycline
      antimicrobial tigecycline, and a suite of comparator agents, against an array of
      clinically important bacterial pathogens worldwide. In this report, we examine
      the activity of tigecycline and comparators against a collection of 13,245
      clinical isolates, both Gram-positive (n = 4,078 and Gram-negative (n = 9,167),
      collected from 27 centres in Italy between 2004 and 2011. Susceptibility was
      established according to Clinical Laboratory Standards Institute guidelines.
      Tigecycline and linezolid exhibited very good activity against Gram-positive
      pathogens, with MIC90s ranging from 0.06 to 0.25 mg/L and 1-4 mg/L, respectively;
      vancomycin and the carbapenems also showed good activity against select Gram
      positive pathogens. Tigecycline was the most active agent against Gram-negative
      pathogens (except P. aeruginosa), with MIC90s ranging from 0.25-2 mg/L (16 mg/L
      for P. aeruginosa). Amikacin and the carbapenems also possessed good activity
      against many Gram-negative pathogens here. ESBL-positive E. coli increased in
      prevalence from 2004 to 2011, while ESBL-positive Klebsiella spp., vancomycin
      resistant enterococci and MRSA decreased in prevalence. Linezolid, tigecycline
      and vancomycin susceptibility were very stable over the course of this study,
      while susceptibility to ampicillin, piperacillin-tazobactam, ceftriaxone and
      levofloxacin varied over time according to pathogen; minocycline and cefepime
      susceptibility among several pathogens decreased during this study. 

PMID- 24287462
TI  - Nanoparticles as Drug Delivery Systems in Cancer Medicine: Emphasis on RNAi
      Containing Nanoliposomes.
AB  - Nanomedicine is a growing research field dealing with the creation and
      manipulation of materials at a nanometer scale for the better treatment,
      diagnosis and imaging of diseases. In cancer medicine, the use of nanoparticles
      as drug delivery systems has advanced the bioavailability, in vivo stability,
      intestinal absorption, solubility, sustained and targeted delivery, and
      therapeutic effectiveness of several anticancer agents. The expansion of novel
      nanoparticles for drug delivery is an exciting and challenging research filed, in
      particular for the delivery of emerging cancer therapies, including small
      interference RNA (siRNA) and microRNA (miRNAs)-based molecules. In this review,
      we focus on the currently available drug delivery systems for anticancer agents.
      In addition, we will discuss the promising use of nanoparticles for novel cancer
      treatment strategies. 

PMID- 24287464
TI  - Structural bioinformatics and protein docking analysis of the molecular chaperone
      kinase interactions: towards allosteric inhibition of protein kinases by
      targeting the hsp90-cdc37 chaperone machinery.
AB  - A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of
      protein kinase clients and supporting kinase functional activity is essential for
      the integrity and viability of signaling pathways involved in cell cycle control
      and organism development. Despite significant advances in understanding structure
      and function of molecular chaperones, the molecular mechanisms and guiding
      principles of kinase recruitment to the chaperone system are lacking quantitative
      characterization. Structural and thermodynamic characterization of Hsp90-Cdc37
      binding with protein kinase clients by modern experimental techniques is highly
      challenging, owing to a transient nature of chaperone-mediated interactions. In
      this work, we used experimentally-guided protein docking to probe the allosteric
      nature of the Hsp90-Cdc37 binding with the cyclin-dependent kinase 4 (Cdk4)
      kinase clients. The results of docking simulations suggest that the kinase
      recognition and recruitment to the chaperone system may be primarily determined
      by Cdc37 targeting of the N-terminal kinase lobe. The interactions of Hsp90 with
      the C-terminal kinase lobe may provide additional "molecular brakes" that can
      lock (or unlock) kinase from the system during client loading (release) stages.
      The results of this study support a central role of the Cdc37 chaperone in
      recognition and recruitment of the kinase clients. Structural analysis may have
      useful implications in developing strategies for allosteric inhibition of protein
      kinases by targeting the Hsp90-Cdc37 chaperone machinery. 

PMID- 24287465
TI  - Hedgehog pathway blockade inhibits melanoma cell growth in vitro and in vivo.
AB  - Previous reports have demonstrated a role for hedgehog signaling in melanoma
      progression, prompting us to explore the therapeutic benefit of targeting this
      pathway in melanoma. We profiled a panel of human melanoma cell lines and control
      melanocytes for altered expression of hedgehog pathway members and determined the
      consequences of both genetic and pharmacological inhibition of the hedgehog
      pathway activator Smoothened (SMO) in melanoma, both in vitro and in vivo. We
      also examined the relationship between altered expression of hedgehog pathway
      mediators and survival in a well-characterized cohort of metastatic melanoma
      patients with prospectively collected follow up information. Studies revealed
      that over 40% of the melanoma cell lines examined harbored significantly elevated
      levels of the hedgehog pathway mediators SMO, GLI2, and PTCH1 compared to
      melanocytes (p < 0.05). SMO inhibition using siRNA and the small molecule
      inhibitor, NVP-LDE-225, suppressed melanoma growth in vitro, particularly in
      those cell lines with moderate SMO and GLI2 expression. NVP-LDE-225 also induced
      apoptosis in vitro and inhibited melanoma growth in a xenograft model. Gene
      expression data also revealed evidence of compensatory up-regulation of two other
      developmental pathways, Notch and WNT, in response to hedgehog pathway
      inhibition. Pharmacological and genetic SMO inhibition also downregulated genes
      involved in human embryonic stem cell pluripotency. Finally, increased SMO
      expression and decreased expression of the hedgehog pathway repressor GLI3
      correlated with shorter post recurrence survival in metastatic melanoma patients.
      Our data demonstrate that hedgehog pathway inhibition might be a promising
      targeted therapy in appropriately selected metastatic melanoma patients. 

PMID- 24287466
TI  - Kramer et al. respond to "Composite outcomes and paradoxes".

PMID- 24287467
TI  - A case-control study of long-term exposure to ambient volatile organic compounds
      and lung cancer in Toronto, Ontario, Canada.
AB  - Few studies have investigated associations between nonoccupational exposure to
      ambient volatile organic compounds and lung cancer. We conducted a case-control
      study of 445 incident lung cancers and 948 controls (523 hospital, 425 general
      population) in Toronto, Ontario, Canada, between 1997 and 2002. Participants
      provided information on several risk factors, including tobacco use, secondhand
      exposure to cigarette smoke, obesity, and family history of cancer. Exposure to
      benzene, hydrocarbons, and nitrogen dioxide was estimated using land-use
      regression models. Exposures were linked to residential addresses to estimate
      exposure at the time of interview, 10 years before interview, and across past
      residences (time-weighted average). Logistic regression was used to estimate
      adjusted odds ratios. Analyses involving the population-based controls found that
      an interquartile-range increase in the time-weighted average benzene
      concentration (0.15 ug/m(3)) across previous residences was associated with lung
      cancer (odds ratio = 1.84, 95% confidence interval: 1.26, 2.68). Similarly, an
      interquartile-range increase in the time-weighted average nitrogen dioxide
      concentration (4.8 ppb) yielded an odds ratio of 1.59 (95% confidence interval:
      1.19, 2.12). Our study suggests that long-term exposure to ambient volatile
      organic compounds and nitrogen dioxide at relatively low concentrations is
      associated with lung cancer. Further work is needed to evaluate joint
      relationships between these pollutants, smoking, and lung cancer. 

PMID- 24287468
TI  - Analyzing risks of adverse pregnancy outcomes.
AB  - Approaches for analyzing the risks of adverse pregnancy outcomes have been the
      source of much debate and many publications. Much of the problem, in our view, is
      the conflation of time at risk with gestational age at birth (or birth weight, a
      proxy for gestational age). We consider the causal questions underlying such
      analyses with the help of a generic directed acyclic graph. We discuss competing
      risks and populations at risk in the context of appropriate numerators and
      denominators, respectively. We summarize 3 different approaches to quantifying
      risks with respect to gestational age, each of which addresses a distinct
      etiological or prognostic question (i.e., cumulative risk, prospective risk, or
      instantaneous risk (hazard)) and suggest the appropriate denominators for each.
      We show how the gestational age-specific risk of perinatal death (PND) can be
      decomposed as the product of the gestational age-specific risk of birth and the
      risk of PND conditional on birth at a given gestational age. Finally, we
      demonstrate how failure to consider the first of these 2 risks leads to selection
      bias. This selection bias creates the well-known crossover paradox, thus
      obviating the need to posit common causes of early birth and PND other than the
      study exposure. 

PMID- 24287469
TI  - Villeneuve et al. Respond to "impact of air pollution on lung cancer".

PMID- 24287470
TI  - Invited commentary: composite outcomes as an attempt to escape from selection
      bias and related paradoxes.
AB  - This commentary reviews the recent history of explanations to crossover paradoxes
      such as the birth weight and gestational age paradoxes, with a special emphasis
      on the current proposal by Kramer et al. in this issue of the Journal (Am J
      Epidemiol. 2014;179(3):361-367). We contend that the causal structure of these
      paradoxes is essentially identical to that of several well-known selection
      biases. We then consider the pros and cons of using composite outcomes to
      circumvent these selection biases. 

PMID- 24287471
TI  - Invited commentary: epidemiologic studies of the impact of air pollution on lung
      cancer.
AB  - In this issue of the Journal, Villeneuve et al. (Am J Epidemiol. 2014;179(4):443
      451) present epidemiologic evidence supporting the literature on the adverse
      effects of air pollution on risk of lung cancer. They found that ambient exposure
      to volatile organic compounds, especially when measured at longer time scales,
      was associated with increased odds of lung cancer in citizens of Toronto,
      Ontario, Canada, between 1997 and 2002. Specifically, in fully adjusted models,
      they observed that an interquartile-range increase in benzene concentration was
      associated with an odds ratio of 1.51 (95% confidence interval: 1.13, 2.01) using
      exposure at the time of interview. The odds ratio increased to 1.84 (95%
      confidence interval: 1.26, 2.68) when time-weighted exposure at all previous
      addresses was considered. They obtained similar results for exposure to nitrogen
      dioxide. These findings add weight to the substantial (and rapidly growing) body
      of literature on the relation of air pollution with lung cancer risk, as well as
      illustrate important aspects of the effects of different exposure assessment
      choices and potential sources of key interest. 

PMID- 24287472
TI  - Highly luminescent and photostable core-shell dye nanoparticles for high
      efficiency bioimaging.
AB  - We developed core-shell silica-coated dye nanoparticles as highly bright and
      ultrastable red-emitting fluorescent probes for long-term cellular imaging and
      ultrasensitive in vivo animal imaging. 

PMID- 24287473
TI  - Auraptenol attenuates vincristine-induced mechanical hyperalgesia through
      serotonin 5-HT1A receptors.
AB  - Common chemotherapeutic agents such as vincristine often cause neuropathic pain
      during cancer treatment in patients. Such neuropathic pain is refractory to
      common analgesics and represents a challenging clinical issue. Angelicae
      dahuricae radix is an old traditional Chinese medicine with demonstrated
      analgesic efficacy in humans. However, the active component(s) that attribute to
      the analgesic action have not been identified. This work described the anti
      hyperalgesic effect of one coumarin component, auraptenol, in a mouse model of
      chemotherapeutic agent vincristine-induced neuropathic pain. We reported that
      auraptenol dose-dependently reverted the mechanical hyperalgesia in mice within
      the dose range of 0.05-0.8 mg/kg. In addition, the anti-hyperalgesic effect of
      auraptenol was significantly blocked by a selective serotonin 5-HT1A receptor
      antagonist WAY100635 (1 mg/kg). Within the dose range studied, auraptenol did not
      significantly alter the general locomotor activity in mice. Taken together, this
      study for the first time identified an active component from the herbal medicine
      angelicae dahuricae radix that possesses robust analgesic efficacy in mice. These
      data support further studies to assess the potential of auraptenol as a novel
      analgesic for the management of neuropathic pain.

PMID- 24287474
TI  - Modeling lineage and phenotypic diversification in the New World monkey
      (Platyrrhini, Primates) radiation.
AB  - Adaptive radiations that have taken place in the distant past can now be more
      thoroughly studied with the availability of large molecular phylogenies and
      comparative data drawn from extant and fossil species. Platyrrhines are a good
      example of a major mammalian evolutionary radiation confined to a single
      continent, involving a relatively large temporal scale and documented by a
      relatively small but informative fossil record. Here, we present comparative
      evidence using data on extant and fossil species to explore alternative
      evolutionary models in an effort to better understand the process of platyrrhine
      lineage and phenotypic diversification. Specifically, we compare the likelihood
      of null models of lineage and phenotypic diversification versus various models of
      adaptive evolution. Moreover, we statistically explore the main ecological
      dimension behind the platyrrhine diversification. Contrary to the previous
      proposals, our study did not find evidence of a rapid lineage accumulation in the
      phylogenetic tree of extant platyrrhine species. However, the fossil-based
      diversity curve seems to show a slowdown in diversification rates toward present
      times. This also suggests an early high rate of extinction among lineages within
      crown Platyrrhini. Finally, our analyses support the hypothesis that the
      platyrrhine phenotypic diversification appears to be characterized by an early
      and profound differentiation in body size related to a multidimensional niche
      model, followed by little subsequent change (i.e., stasis). 

PMID- 24287475
TI  - Laparoscopic upper pole splenectomy of the simple splenic cyst.
AB  - Splenic cysts are rare clinic entities. Non-parasitic cysts are the most frequent
      cystic lesions of the spleen. In the last decade acknowledgment of the importance
      of the spleen function, along with development of imaging methods and surgery
      technics, allowed a conservative approach to be increasingly considered as the
      best approach in splenic cysts treatment. We present the case of a 34-year-old
      woman with an asymptomatic simple splenic cyst in the upper pole incidentally
      diagnosed in a thoracic CT. A laparoscopic upper pole splenectomy was performed
      on the patient, with no complications. Despite the rareness of this procedure and
      the fact that it was used in a simple splenic cyst, this article emphasises the
      idea that this approach is safe, reproducible and advantageous for the patient. 

PMID- 24287476
TI  - Meningeal calcification in basal cell nevus syndrome.

PMID- 24287477
TI  - Splenectomy complicated by sustained extreme thrombocytosis and extensive
      portosplenomesenteric vein thrombosis in pyrimidine 5'-nucleotidase deficiency.
AB  - Reactive and redistributional thrombocytosis is a well-known postsplenectomy
      occurrence .Usually it is transient and it rarely reaches extreme levels. We
      report a rare case of haemolytic anaemia where splenectomy was carried out
      following trauma to a massively enlarged spleen and was followed by extreme
      sustained thrombocytosis associated with extensive portal, splenic and mesenteric
      vein thrombosis despite standard antithrombotic prophylaxis. 

PMID- 24287478
TI  - Hygroma in a 23-year-old man.
AB  - We describe a 23-year-old man with a cystic hygroma on the right side of his
      lower neck. Cystic hygromas are uncommon congenital lesions of the lymphatic
      system and are often diagnosed before the age of 2. The finding of a cystic
      hygroma is rare in adults. We report the results regarding a cystic hygroma in a
      23-year-old man. An initial physical examination was performed, followed by an
      ultrasound examination and CT. Surgical excision was the treatment of choice.
      Adequate imaging and physical examination of lateral neck masses in adults are
      needed to confirm the diagnosis. 

PMID- 24287479
TI  - Ocular quinine toxicity in a sleepwalker.
AB  - A 55-year-old woman presented to the emergency department following an episode of
      severe visual impairment, headache, dizziness and confusion. The patient had been
      taking quinine sulfate as long-term medication for leg cramps. During an episode
      of sleepwalking, the patient had taken an overdose of quinine sulfate. Following
      a thorough investigation and assessment, a diagnosis of ocular quinine toxicity
      was made. We present this case and highlight the risks of quinine prescription. 

PMID- 24287480
TI  - Early aetiological agent identification of osteomyelitis with the Light Cycler
      SeptiFast test from peripheral blood.
AB  - The commercial real-time PCR SeptiFast test allows identification of 25 bacterial
      and fungal species directly from peripheral blood in patients with bloodstream
      infections. A 22-year-old Caucasian woman reported an open femur fracture
      requiring a two step surgical procedure. After the second procedure the patient
      manifested sepsis and Enterobacter cloacae/aerogenes DNA was detected in the
      peripheral blood with the SeptiFast. Thereafter, femur osteomyelitis was
      diagnosed and E cloacae was cultured from intraoperative bone samples. The
      patient completed a 3-month course of antimicrobial therapy. Five months after
      therapy was discontinued, the patient remained symptom free, but delayed bone
      consolidation occurs. Molecular methods to identify aetiological agents in blood,
      in addition to conventional cultures, could represent an advantageous tool in
      clinical practice also in patients with post-traumatic bone infections. 

PMID- 24287481
TI  - The development of Fournier's gangrene following rubber band ligation of
      haemorrhoids.
AB  - The development of Fournier's gangrene in an 80-year-old male patient with
      diabetes after a routine outpatient haemorrhoid banding procedure is described.
      Four days following the procedure, the patient noticed an increasing amount of
      pain and swelling of the perianal region. When the patient presented to the
      emergency department 18 days later, immediate radical debridement of ischiorectal
      necrotic tissue was performed. A defunctioning loop sigmoid colostomy was also
      formed. Subsequent operations required excision of the scrotum and
      abdominoperineal excision of the rectum. Histology studies later confirmed the
      presence of necrotising fasciitis. The case acts as a reminder that clinicians
      should maintain a high index of suspicion for high-risk patients still suffering
      from problems following the procedure. 

PMID- 24287482
TI  - Lemierre syndrome: more than just a sore throat.

PMID- 24287483
TI  - Bisphosphonate-induced atypical subtrochanteric femoral fracture.
AB  - The use of bisphosphonates (BPs) is universally accepted in the management of
      osteoporosis. However, a small percentage of patients have been recognised to
      develop atypical subtrochanteric fractures of the femur with the prolonged use of
      BPs. We report a rare case of bilateral insufficiency lesions in the proximal
      femora, where a major subtrochanteric fracture developed with a minor fall. This
      was successfully treated with internal fixation using proximal femoral nail. 

PMID- 24287484
TI  - Baboon syndrome: an unusual complication arising from antibiotic treatment of
      tonsillitis and review of the literature.
AB  - A 40-year-old man presented with sore throat and fevers associated with
      bilaterally enlarged and inflamed tonsils. A clinical diagnosis of tonsillitis
      was made and the patient received intravenous benzylpenicillin. Over subsequent
      days, the patient developed a macular rash over both groins, buttocks and
      axillae, with necrotic patches in the groins. An assumptive diagnosis of
      necrotising fasciitis was made. The patient underwent urgent groin biopsy and was
      started on broad spectrum antibiotics. No organisms were seen on Gram stain.
      Following a multidisciplinary discussion, the patient was diagnosed with baboon
      syndrome (symmetrical drug-related intertriginous and flexural exanthema). He was
      treated with oral steroid along with topical agents. Baboon syndrome can develop
      following penicillin administration. Given the widespread use of penicillin
      antibiotics to treat tonsillitis and many other conditions, it is important that
      medical staff recognise the side effects of these medications. 

PMID- 24287485
TI  - Pneumocystis jerovecii pneumonia in a patient with untreated chronic lymphocytic
      leukaemia: a novel case and postulations concerning the mechanism.
AB  - Chronic lymphocytic leukaemia (CLL), even when severe, is not directly associated
      with opportunistic infections. Opportunistic infections that occur with CLL are
      almost exclusively related to immunosuppression caused by chemotherapeutic drugs
      used to treat CLL. We report a case of Pneumocystis jirovecii (PJ) pneumonia that
      occurred in a patient with untreated CLL with pulmonary involvement. We suspect
      that PJ pneumonia resulted from an inadequate immune response in the lung
      parenchyma resulting from excessive local accumulation of CLL cells. 

PMID- 24287486
TI  - Laser patterning of transparent conductive metal nanowire coatings: simulation
      and experiment.
AB  - Transparent and electrically conductive metal nanowire networks are possible
      replacements for costly indium tin oxide (ITO) films in many optoelectronic
      devices. ITO films are regularly patterned using pulsed lasers so similar
      technologies could be used for nanowire coatings to define electrode structures.
      Here, the effects of laser irradiation on conducting silver nanowire coatings are
      simulated and then investigated experimentally for networks formed by spray
      deposition onto transparent substrates. The ablation threshold fluence is found
      experimentally for such nanowire networks and is then related to film thickness.
      An effective model using finite-element heat transfer analysis is examined to
      look at energy dissipation through these nanowire networks and used to understand
      mechanisms at play in the laser-material interactions. It is demonstrated that
      the three-dimensional nature of these coatings and the relative ratios of the
      rates of lateral to vertical heat diffusion are important controlling parameter
      affecting the ablation threshold. 

PMID- 24287489
TI  - Hydrogen cyanide, a volatile biomarker of Pseudomonas aeruginosa infection.
AB  - Since we first recognized the regular presence of gaseous hydrogen cyanide, HCN,
      in the headspace of plate cultures of the bacterium Pseudomonas aeruginosa, PA,
      derived from sputum of cystic fibrosis, CF, patients, and following crucial ion
      chemistry research that allowed accurate quantification of gaseous HCN by
      selected ion flow tube mass spectrometry, we have carried out many further in
      vitro and in vivo studies. We have measured HCN in the headspace of various PA
      culture types, planktonic and biofilm, significant numbers of genetically
      identified PA strains together with studies of HCN in the mouth-exhaled and nose
      exhaled breath of healthy children and adults and those with CF. The major
      findings are: (i) virtually all strains of PA release HCN when cultured in vitro,
      as shown by the investigation of more than 150 genetically differentiated
      strains, both mucoid and non-mucoid. (ii) HCN is present in the mouth-exhaled
      breath of adults and children, but is at lower concentrations in children. Its
      concentration is below the detection limit in nose-exhaled breath of healthy
      people. (iii) HCN is present in both mouth-exhaled and nose-exhaled breath of
      patients with CF, suggesting the presence of PA in the lower airways as indicated
      by clinical microbiological cultures. With confirmation of these findings by
      further research and clinical trials, nose-exhaled breath HCN measurements could
      be an additional diagnostic tool to detect the early presence of PA in the lower
      airways and a non-invasive monitor to enhance the likelihood of its eradication.

PMID- 24287487
TI  - Cyclin D1 induction of Dicer governs microRNA processing and expression in breast
      cancer.
AB  - Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates the
      pRB protein and promotes G1/S cell-cycle progression and oncogenesis. Dicer is a
      central regulator of miRNA maturation, encoding an enzyme that cleaves double
      stranded RNA or stem-loop-stem RNA into 20-25 nucleotide long small RNA,
      governing sequence-specific gene silencing and heterochromatin methylation. The
      mechanism by which the cell cycle directly controls the non-coding genome is
      poorly understood. Here we show that cyclin D1(-/-) cells are defective in pre
      miRNA processing which is restored by cyclin D1a rescue. Cyclin D1 induces Dicer
      expression in vitro and in vivo. Dicer is transcriptionally targeted by cyclin
      D1, via a cdk-independent mechanism. Cyclin D1 and Dicer expression significantly
      correlates in luminal A and basal-like subtypes of human breast cancer. Cyclin D1
      and Dicer maintain heterochromatic histone modification (Tri-m-H3K9). Cyclin D1
      mediated cellular proliferation and migration is Dicer-dependent. We conclude
      that cyclin D1 induction of Dicer coordinates microRNA biogenesis. 

PMID- 24287490
TI  - Optomechanical interface for probing matter-wave coherence.
AB  - We combine matter-wave interferometry and cavity optomechanics to propose a
      coherent matter-light interface based on mechanical motion at the quantum level.
      We demonstrate a mechanism that is able to transfer non-classical features
      imprinted on the state of a matter-wave system to an optomechanical device,
      transducing them into distinctive interference fringes. This provides a reliable
      tool for the inference of quantum coherence in the particle beam. Moreover, we
      discuss how our system allows for intriguing perspectives, paving the way to the
      construction of a device for the encoding of quantum information in matter-wave
      systems. Our proposal, which highlights previously unforeseen possibilities for
      the synergistic exploitation of these two experimental platforms, is explicitly
      based on existing technology, available and widely used in current cutting-edge
      experiments. 

PMID- 24287491
TI  - Effect of essential oils on pathogenic bacteria.
AB  - The increasing resistance of microorganisms to conventional chemicals and drugs
      is a serious and evident worldwide problem that has prompted research into the
      identification of new biocides with broad activity. Plants and their derivatives,
      such as essential oils, are often used in folk medicine. In nature, essential
      oils play an important role in the protection of plants. Essential oils contain a
      wide variety of secondary metabolites that are capable of inhibiting or slowing
      the growth of bacteria, yeasts and moulds. Essential oils and their components
      have activity against a variety of targets, particularly the membrane and
      cytoplasm, and in some cases, they completely change the morphology of the cells.
      This brief review describes the activity of essential oils against pathogenic
      bacteria. 

PMID- 24287492
TI  - Glioblastoma multiforme therapy and mechanisms of resistance.
AB  - Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a
      heterogeneous population of cells that are highly infiltrative, angiogenic and
      resistant to chemotherapy. The current standard of care, comprised of surgical
      resection followed by radiation and the chemotherapeutic agent temozolomide, only
      provides patients with a 12-14 month survival period post-diagnosis. Long-term
      survival for GBM patients remains uncommon as cells with intrinsic or acquired
      resistance to treatment repopulate the tumor. In this review we will describe the
      mechanisms of resistance, and how they may be overcome to improve the survival of
      GBM patients by implementing novel chemotherapy drugs, new drug combinations and
      new approaches relating to DNA damage, angiogenesis and autophagy. 

PMID- 24287496
TI  - Three p-carboxyphenyl groups possessing zinc porphyrins: efficient, stable, and
      cost-effective sensitizers for dye-sensitized solar cells.
AB  - Zinc porphyrins possessing three p-carboxyphenyl anchoring groups with various
      substituents were prepared by a facile three-step route in good yields. Zn1NH3A
      with electron donating and anti-aggregation meso substituents has achieved the
      highest efficiency of 6.10%. These porphyrins with three p-carboxyphenyl groups
      are more stable toward photo-bleaching than their single anchoring group analogs.

PMID- 24287495
TI  - Adult Willingness to Use Email and Social Media for Peer-to-Peer Cancer Screening
      Communication: Quantitative Interview Study.
AB  - BACKGROUND: Adults over age 40 are increasing their use of email and social
      media, raising interest in use of peer-to-peer Internet-based messaging to
      promote cancer screening. OBJECTIVE: The objective of our study was to assess
      current practices and attitudes toward use of email and other e-communication for
      peer-to-peer dialogues on cancer screening. METHODS: We conducted in-person
      interviews with 438 insured adults ages 42-73 in Georgia, Hawaii, and
      Massachusetts. Participants reported on use of email and other e-communication
      including social media to discuss with peers routine health topics including
      breast and colorectal cancer (CRC). We ascertained willingness to share personal
      CRC screening experiences via conversation, postcard, email, or other e
      communication. Health literacy scores were measured. RESULTS: Email had been used
      by one-third (33.8%, 148/438) to discuss routine health topics, by 14.6% (64/438)
      to discuss breast cancer screening, and by 12.6% (55/438) to discuss CRC
      screening. Other e-communication was used to discuss routine health topics
      (11.6%, 51/438), screening for breast cancer (3.9%, 17/438), and CRC (2.3%,
      10/438). In the preceding week, 84.5% (370/438) of participants had used email,
      55.9% (245/438) had used e-communication of some type; 44.3% (194/438) text,
      32.9% (144/438) Facebook, 12.3% (54/438) instant message, 7.1% (31/438) video
      chat, and 4.8% (21/438) Twitter. Many participants were willing to share their
      CRC screening experiences via email (32.4%, 142/438 might be willing; 36.3%,
      159/438 very willing) and via other e-communication (15.8%, 69/438 might be
      willing; 14.4%, 63/438 very willing). Individuals willing to send CRC screening
      emails scored significantly higher on tests of health literacy compared to those
      willing to send only postcards (P<.001). CONCLUSIONS: Many adults are willing to
      use email and e-communication to promote cancer screening to peers. Optimal
      approaches for encouraging peer-to-peer transmission of accurate and appropriate
      cancer screening messages must be studied.

PMID- 24287493
TI  - Aptamer-based therapeutics: new approaches to combat human viral diseases.
AB  - Viruses replicate inside the cells of an organism and continuously evolve to
      contend with an ever-changing environment. Many life-threatening diseases, such
      as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses
      have small genome sizes and high mutability, there is currently a lack of and an
      urgent need for effective treatment for many viral pathogens. One approach that
      has recently received much attention is aptamer-based therapeutics. Aptamer
      technology has high target specificity and versatility, i.e., any viral proteins
      could potentially be targeted. Consequently, new aptamer-based therapeutics have
      the potential to lead a revolution in the development of anti-infective drugs.
      Additionally, aptamers can potentially bind any targets and any pathogen that is
      theoretically amenable to rapid targeting, making aptamers invaluable tools for
      treating a wide range of diseases. This review will provide a broad,
      comprehensive overview of viral therapies that use aptamers. The aptamer
      selection process will be described, followed by an explanation of the potential
      for treating virus infection by aptamers. Recent progress and prospective use of
      aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV,
      Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical
      development of aptamers will also be described. Finally, we will discuss the
      challenges of advancing antiviral aptamer therapeutics and prospects for future
      success. 

PMID- 24287497
TI  - On-chip regeneration of aptasensors for monitoring cell secretion.
AB  - We report on the use of reconfigurable microfluidics for on-chip regeneration of
      aptasensors used for continuous monitoring of cell-secreted products. 

PMID- 24287494
TI  - Antimicrobial peptides.
AB  - The rapid increase in drug-resistant infections has presented a serious challenge
      to antimicrobial therapies. The failure of the most potent antibiotics to kill
      "superbugs" emphasizes the urgent need to develop other control agents. Here we
      review the history and new development of antimicrobial peptides (AMPs), a
      growing class of natural and synthetic peptides with a wide spectrum of targets
      including viruses, bacteria, fungi, and parasites. We summarize the major types
      of AMPs, their modes of action, and the common mechanisms of AMP resistance. In
      addition, we discuss the principles for designing effective AMPs and the
      potential of using AMPs to control biofilms (multicellular structures of bacteria
      embedded in extracellular matrixes) and persister cells (dormant phenotypic
      variants of bacterial cells that are highly tolerant to antibiotics). 

PMID- 24287498
TI  - Influence of zinc on the biokinetics of (65)Zn in brain and whole body and its
      bio-distribution in aluminium-intoxicated rats.
AB  - The present study was designed to understand the influence of zinc (Zn) if any,
      on the biokinetics of (65)Zn in brain as well as whole body and its bio
      distribution following aluminium (Al) treatment to rats. Male Sprague-Dawley rats
      weighing 140-160 g were divided into four different groups viz: normal control,
      aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/L
      in drinking water) and combined aluminium and zinc treated. All the treatments
      were carried out for a total duration of 8 weeks. Al treatment showed a
      significant increase in fast component (Tb1) but revealed a significant decrease
      in slow component (Tb2) of biological half-life in brain as well as in whole
      body. However, Zn supplementation to Al-treated rats reversed the trend in both
      brain and whole body, which indicates a significant decrease in Tb1 component
      while the Tb2 component was significantly increased. Further, Al treatment showed
      an increased percent uptake value of (65)Zn in cerebrum, cerebellum, heart, liver
      and lungs whereas a decrease in uptake was found only in blood. On the other
      hand, there was a significant decline in (65)Zn activity in nuclear and
      mitochondrial fractions of brain of Al-treated rats. However, Zn treatment
      reversed the altered (65)Zn uptake values in different organs as well as in
      various subcellular fractions. The study demonstrates that Zn shall prove to be
      effective in regulating the biokinetics of (65)Zn in brain and whole body and its
      distribution at the tissue and subcellular levels in Al-treated rats. 

PMID- 24287499
TI  - Gender differences and lateralization in the distribution pattern of insulin-like
      growth factor-1 receptor in developing rat hippocampus: an immunohistochemical
      study.
AB  - Numerous investigators have provided data supporting essential roles for insulin
      like growth factor-I (IGF-I) in development of the brain. The aim of this study
      was to immunohistochemically determine the distinct regional distribution pattern
      of IGF-1 receptor (IGF-IR) expression in various portions of newborn rat
      hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14), with comparison
      between male/female and right/left hippocampi. We found an overall significant
      increase in distribution of IGF-IR-positive (IGF-IR+) cells in CA1 from P0 until
      P14. Although, no marked changes in distribution of IGF-IR+ cells in areas CA2
      and CA3 were observed; IGF-IR+ cells in DG decreased until P14. The smallest
      number of immunoreactive cells was present in CA2 and the highest number in DG at
      P0. Moreover, in CA1, CA3, and DG, the number of IGF-IR+ cells was markedly
      higher in both sides of the hippocampus in females. Our data also showed a higher
      mean number of IGF-IR+ cells in the left hippocampus of female at P7. By
      contrast, male pups showed a significantly higher number of IGF-IR+ cells in the
      DG of the right hippocampus. At P14, the mean number of immunoreactive cells in
      CA1, CA3, and DG areas found to be significantly increased in left side of
      hippocampus of males, compared to females. These results indicate the existence
      of a differential distribution pattern of IGF-IR between left-right and male
      female hippocampi. Together with other mechanisms, these differences may underlie
      sexual dimorphism and left-right asymmetry in the hippocampus. 

PMID- 24287501
TI  - Efficient solar photoelectrolysis by nanoporous Mo:BiVO4 through controlled
      electron transport.
AB  - A detailed understanding of doping level, electron diffusion length and
      coefficient, as well as light capture and charge separation efficiencies in
      nanoporous Mo-doped BiVO4 (Mo:BiVO4) photoanodes is obtained using
      photoelectrochemical techniques. Efficient water oxidation is achieved by doping
      with 1.8% Mo, resulting in a several-fold enhancement in photooxidation rate
      versus non-doped BiVO4. Two techniques are used to study the effect of Mo doping
      on the electron transport: (1) an analysis of the front/back illumination ratio
      of incident photon-to-current efficiency and (2) intensity modulated photocurrent
      spectroscopy. These techniques show that Mo doping improves the diffusion
      coefficient four-fold and increases the diffusion length to ca. 300 nm (from 10
      nm for the non-doped material), which is also the empirically-determined optimal
      Mo:BiVO4 film thickness for photoelectrolysis. These films are found to have a
      90% charge separation efficiency and an 80% absorbed photon-to-current
      efficiency, excellent values for metal oxide photoabsorbers. Among the many
      oxygen evolution catalysts studied, surface modification with iron oxyhydroxide
      (FeOOH), a simple earth abundant catalyst, dramatically enhances the water
      oxidation performance of Mo:BiVO4 to an integrated IPCE of 2.41 mA cm(-2) and a
      photocurrent density of 2.77 mA cm(-2) in neutral phosphate at 1.23 V vs. RHE. 

PMID- 24287500
TI  - Prospective study of common variants in CX3CR1 and risk of macular degeneration:
      pooled analysis from 5 long-term studies.
AB  - IMPORTANCE: The CX3CR1 gene is implicated as a candidate gene for age-related
      macular degeneration (AMD) through several lines of evidence. There is
      uncertainty, however, as to whether common genetic variants in CX3CR1 alter risk
      of AMD, since prior studies have been inconsistent and mostly limited to
      evaluation of 2 nonsynonymous variants, T280M (rs3732378) and V249I (rs3732379).
      OBJECTIVE: To determine if common variants in CX3CR1 predict future risk of AMD.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective nested case-control study within 5
      large study populations with long-term follow-up. We measured genotypes for
      T280M, V249I, and 13 other common single-nucleotide polymorphisms (SNPs) of the
      CX3CR1 gene among people who developed AMD (n = 1110, including 369 with
      neovascular AMD) and 2532 age- and sex-matched controls. MAIN OUTCOMES AND
      MEASURES: We determined the incidence rate ratios (RR) and 95% CIs for incidence
      of AMD for each variant and examined interactions with other AMD-associated
      variants and modifiable risk factors. RESULTS: In additive genetic models, we
      identified nonsignificant associations with AMD for T280M (RR, 0.87; P = .07) and
      3 other SNPs, rs2853707 (RR, 0.88; P = .07), rs12636547 (RR, 0.85; P = .10), and
      rs1877563 (RR, 0.84; P = .06), 1 of which, rs2853707, is positioned in the CX3CR1
      promoter region and was associated with neovascular AMD (RR, 0.75; P = .03). We
      observed that a recessive model was a better fit to the data for some SNPs, with
      associations between rs11715522 and AMD (RR, 1.27; P = .03) and between rs2669845
      (RR, 3.10; P = .04), rs2853707 (RR, 0.48; P = .050), and rs9868689 (RR, 0.31; P =
      .02) and neovascular AMD. Moreover, in exploratory analyses, we identified a
      number of possible interactions including between V249I and rs2669845 and dietary
      intake of omega-3 fatty acids (P = .004 and P = .009, respectively) for AMD;
      between rs2669845 and obesity (P = .03) for neovascular AMD; between T280M and
      complement component 3 (C3) R102G for AMD (P = .03); between rs2669845 and Y402H
      in complement factor H for AMD (P = .04); and between rs2669845, rs2853707, and
      V249I and C3 R102G for neovascular AMD (P = .008; .04; and .002, respectively).
      CONCLUSIONS AND RELEVANCE: This study failed to identify significant associations
      between common CX3CR1 variants and AMD after considering the number of SNPs
      analyzed and multiple comparisons. However, we observed evidence consistent with
      recessive modes of association and that an effect of CX3CR1 variants may depend
      on other factors including dietary intake of omega-3 fatty acids, obesity, and
      genotypes at CFH Y402H and C3 R102G. If replicated in other populations, these
      findings would support a role for CX3CR1 in AMD but also suggest that its role
      may involve mechanisms that are independent of the T280M/V249I variations.

PMID- 24287502
TI  - The early discontinuation of palliative chemotherapy in older patients with
      cancer.
AB  - PURPOSE: Older patients with cancer may have an increased risk of early
      discontinuation of active treatment (ED), which results in poor outcome in
      curative or adjuvant settings. We aimed to determine the association between
      survival and ED and to identify predictors of ED in palliative setting. METHODS:
      Ninety-eight patients older than 65 years of age who received a comprehensive
      geriatric assessment (CGA) before palliative first-line chemotherapy were
      analyzed. Clinical information and CGA results were retrieved from electronic
      medical record. CGA included Charlson's co-morbidity index, activities of daily
      living (ADL), instrumental ADL (IADL), Mini-Mental Status Examination, short-form
      of the geriatric depression scale, timed-get-up-and-go test (TGUG), and mini
      nutritional assessment (MNA). ED was defined as no active cancer treatment
      (radiotherapy and/or chemotherapy) beyond palliative first-line chemotherapy.
      Predictors of ED were identified using clinical parameters and CGA. RESULTS:
      Active treatment was discontinued after first-line chemotherapy in 30 patients
      during median follow-up period of 15.1 months. ED after first-line chemotherapy
      was associated with shorter overall survival (OS; median OS = 3.1 vs. 14.7 months
      in patients with ED compared with patients without ED, p < 0.001). Eastern
      Cooperative Oncology Group performance status, living alone, ADL, IADL, MNA, and
      TGUG were associated with ED (p = 0.001, p = 0.048, p = 0.001, p < 0.001, p <
      0.001, p = 0.002, respectively). In multivariable analysis, malnutrition and
      dependent IADL were the independent predictive factors for ED (odds ratio = 5.03;
      95 % confidence interval = 1.50-16.87: odds ratio = 3.06; confidence interval =
      1.03-9.12, respectively). CONCLUSIONS: ED was associated with shorter OS in older
      patients with cancer. Malnutrition and dependent IADL were identified as
      independent predictive factors for ED.

PMID- 24287503
TI  - Information needs of early-stage prostate cancer patients: within- and between
      group agreement of patients and health professionals.
AB  - PURPOSE: The aims of this study were to analyze agreement on information needs
      within a group of early-state prostate cancer patients and to compare information
      preferences of patients with the view of health-care professionals about
      patients' needs. METHODS: Sample consists of patients (n = 128) and six subgroups
      of health-care professionals (urologists, n = 32; nurses, n = 95; radiotherapy
      technologists (RTTs), n = 36; medical oncologists, n = 19; radiation oncologists,
      n = 12; general practitioners (GPs), n = 10). Information needs have been
      assessed with 92 questions concerning prostate cancer and its treatment.
      Respondents judged the importance of addressing each question. Within- and
      between-group agreements of patients and health-care professional groups were
      estimated with raw agreement indices as well as chance-corrected Kappa and Gwet's
      AC1 measures. Finally, group-specific core items rated with high importance as
      well as high agreement were defined. RESULTS: Patients rated on average (median)
      half, i.e., 51 out 92 items as essential (interquartile range (IQR) = 36-66), 26
      items as desired (IQR = 14-38), and 10 items as avoidable (IQR = 2-22). Within
      group agreement on the presented information topics is modest for any
      participating group (AC1(patients)= 0.319; AC1(professionals) = 0.295-0.398).
      Agreement between patients and professionals is low too (AC1 = 0.282-0.329).
      Defining group-specific core sets of information topics results in 51 items being
      part of at least one core set. Concordance of the item core sets of patients and
      professionals is moderate with kappa = 0.38-0.66, sensitivity of professionals'
      core sets for patients' preferences varies between 56 and 74%. CONCLUSIONS:
      Results emphasize the need for dialogue between doctor/professional and patient
      in identifying the information needed by individual patients and support the
      importance of shared decision making.

PMID- 24287504
TI  - Ideal care and the realities of practice: interdisciplinary relationships in the
      management of advanced cancer patients in Australian emergency departments.
AB  - PURPOSE: Over the course of their illness, a person with cancer is likely to see
      a number of different healthcare professionals, including those in the emergency
      department (ED). There is limited research examining the interaction and
      communication between the involved healthcare professionals when such a patient
      presents to the ED. This study aimed to explore the views and experiences of
      interdisciplinary interactions of healthcare professionals caring for patients
      with advanced cancer who present to the ED. METHODS: Focus groups and
      semistructured interviews were conducted with clinical staff working in ED,
      oncology and community and hospital-based palliative care services. Interviews
      and focus groups were recorded and transcribed verbatim. Thematic analysis was
      undertaken by three researchers independently. These themes were then discussed
      by the wider team and consensus reached on themes and subthemes. RESULTS: Eighty
      three healthcare professionals participated in focus groups, and 11 were
      interviewed. The over-arching theme to emerge was one of a conflict between ideal
      care and the realities of practice, particularly arising where clinicians from
      different services were required to work together to provide care. This idea was
      further understood through a series of subthemes including communication,
      decision-making and understanding of other services. CONCLUSIONS: Participants
      articulated agreed upon ideals of optimal care for advanced cancer patients
      across all three services, however there was frequently discord between these
      ideals and the actual care provided. Service demands and the day-to-day stressors
      of practice appeared to influence people's actions and engender conflict.

PMID- 24287505
TI  - Direct costs associated with febrile neutropenia in inpatients with hematological
      diseases in Singapore.
AB  - PURPOSE: This prospective cohort study aims to investigate the direct
      hospitalization costs incurred during febrile neutropenia (FN) in inpatients with
      underlying hematological conditions and also to elucidate the factors associated
      with a high cost of managing febrile neutropenia. METHODS: Patients with
      underlying hematological conditions and documented FN were recruited between
      October 2008 and February 2011. FN-related costs included all costs incurred from
      the first day of FN until the last day of antibiotics prescribed. Relevant
      clinical factors were analyzed using generalized estimating equation models to
      elucidate the factors that were associated with higher costs of FN. RESULTS: A
      total of 175 patients were recruited with 303 documented episodes of FN. In non
      transplant patients, 75.6 % of the FN episodes occurred. The median and mean cost
      incurred for each FN episode was USD9,060 (interquartile range = USD5,047-16,631)
      and USD15,298 (standard deviation +/- USD17,459), respectively, accounting for
      approximately 38 % of the median total hospitalization cost and 37 % of the mean
      total hospitalization cost. The ward charges (44.1 %) constituted the largest
      component of the cost, followed by the laboratory charges (27.3 %) and
      medications (18.7 %), of which antimicrobials constituted 9.6 % of the cost of
      FN. The factors associated with higher costs of FN include cytomegalovirus
      reactivation (p < 0.001), longer duration of antibiotics (p < 0.001), lower
      absolute neutrophil count nadir (p < 0.001), allogeneic stem cell transplantation
      (p < 0.01), and diagnosis of invasive fungal infection (p < 0.05). CONCLUSION:
      The economic cost of management of FN in hematology inpatients is considerable
      and in addition to the overall risk of mortality for this condition. Strategies
      to reduce FN or ameliorate its costs are essential for this group of patients.

PMID- 24287506
TI  - Changing communication needs and preferences across the cancer care trajectory:
      insights from the patient perspective.
AB  - PURPOSE: In this program of research, we sought to expand our understanding of
      how cancer patients' communication needs and preferences change across the course
      of their illness trajectory. To address known limitations in the empirical
      knowledge base, we designed a study capitalizing on representative patient
      reports as they occurred within time and across experience obtaining care for
      this disease. METHODS: We used a longitudinal cohort design informed by
      interpretive description methodology to follow 125 patients over a multi-year
      period as they reflected on their ongoing experiences with cancer care
      communication. RESULTS: In relation to each phase of their cancer care
      trajectory, patients identified tension points and contextual challenges
      impinging on what they felt constituted helpful and unhelpful patient-provider
      communication. CONCLUSIONS: Findings from this study create a dynamic portrait of
      how we can better inform communication approaches and interventions through
      interpretations of population knowledge and individual experience.

PMID- 24287507
TI  - "A quiet still voice that just touches": music's relevance for adults living with
      life-threatening cancer diagnoses.
AB  - PURPOSE: Music has historically aided health and loss-adaptation, however, cancer
      patients' experience of music for self-care is not well understood. This study
      examines adult cancer patients' views about music's role before and after
      diagnosis. METHODS: Constructivist approach, with grounded theory informed design
      using convenience, snowball and theoretical sampling. Patients from Australian
      metropolitan cancer and hospice settings completed demographic questionnaires and
      participated in semi-structured interviews. Qualitative inter-rater reliability
      was applied. RESULTS: Fifty-two patients reported comparable time spent
      experiencing music pre-post diagnosis. Music may remain incidental; however, many
      patients adapt music usage to ameliorate cancer's aversive effects. Patients
      often draw from their musical lives and explore unfamiliar music to: remain
      connected with pre-illness identities; strengthen capacity for enduring
      treatment, ongoing survival (even when knowing "you're going to die"), or facing
      death; reframe upended worlds; and live enriched lives. Patients can ascribe
      human or physical properties to music when describing its transformative effects.
      Familiar lyrics maybe reinterpreted, and patients' intensified emotional
      reactions to music can reflect their threatened mortality. Sometimes music
      becomes inaccessible, elusive, and/or intensifies distress and is avoided.
      Families', friends' and professionals' recognition of patients' altered musical
      lives and music-based suggestions can extend patients' use of music for self
      care. CONCLUSION: Health professionals can support patients by inquiring about
      their music behaviours and recognising that altered music usage may signify
      vulnerability. Although commonly recommended, hospital concerts and music
      broadcasts need sensitive delivery. Patients' preferred music should be available
      in diagnostic, treatment and palliative settings because it can promote endurance
      and life enrichment.

PMID- 24287508
TI  - Psychometric validation of the functional assessment of cancer therapy--brain
      (FACT-Br) for assessing quality of life in patients with brain metastases.
AB  - OBJECTIVE: This study aimed to test the reliability, psychometric, and clinical
      validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT
      Br) in patients with brain metastases. METHODS: Patients with brain metastases
      were interviewed using the FACT-Br (including the FACT-general) 1 week prior to
      treatment. All patients completed a follow-up assessment 1 month post-treatment.
      Patients with a good performance status and receiving stereotactic radiosurgery
      completed an additional 1 week follow-up assessment after the initial baseline
      interview to assess test-retest reliability. RESULTS: Forty patients had complete
      1 month follow-up data. Ten of these patients also completed the 1 week follow-up
      assessment from baseline. The median Karnofsky performance status of patients was
      80 and the median age was 64 years. All subscales of the FACT-Br were found to be
      conceptually related (except for two correlations) using the following subscales:
      physical well-being (PWB), social/family well-being (SWB), emotional well-being
      (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale
      (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent
      reliability, except for the SWB scale which revealed good reliability. The FACT
      Br scores showed no significant change in the quality of life (QoL) of patients
      from baseline to 1 month follow-up. CONCLUSION: The use of the combined FACT-G
      and FACT-Br Subscale to assess QoL specifically in patients with brain metastases
      has successfully undergone psychometric validation. Future clinical trials should
      use the FACT-G and FACT-Br Subscale to assess QoL in this patient population.

PMID- 24287509
TI  - Perception and fulfillment of cancer patients' nursing professional social
      support needs: from the health care personnel point of view.
AB  - PURPOSE: This study aimed to (1) explore the needs of cancer patients regarding
      common nursing professional social support from the perspective of physicians and
      nurses, (2) identify what type of needs clinical nurses actually fulfill and what
      remains to be improved, and (3) analyze the potential reasons for the gap between
      the identified needs and those that are fulfilled. METHODS: A qualitative
      approach using focus group interviews was adopted to explore the perception and
      provision of cancer patients' needs regarding nursing professional social
      support. A purposive sample of 32 health care professionals was recruited from
      two teaching hospitals in Anhui province, China. Five focus group interviews were
      conducted and all interviews were tape-recorded and transcribed verbatim. A
      content analysis was performed with the data. RESULTS: The healthcare
      professionals perceived various nursing professional support needs of cancer
      patients; these include informational, emotional/psychological, and technical
      support needs; the mobilization of social resources; and palliative care during
      certain stages. The findings also indicated that there are still many unmet
      needs, especially needs related to the mobilization of social resources and
      palliative care. The reasons for the deficiencies in the fulfillment of these
      needs varied and included both subjective and objective aspects, such as the
      patients' lack of awareness of how to search for professional support, a shortage
      of professional staff, and the lack of a culturally appropriate assessment tool.
      CONCLUSIONS: Cancer patients' supportive care needs were not always fully
      provided by nurses, even when these needs were identified by healthcare
      professionals. Nursing professional social support needs should be assessed
      quickly and effectively so that the appropriate interventions can be offered to
      cancer patients.

PMID- 24287512
TI  - Anti-phospholipid antibodies.

PMID- 24287510
TI  - Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a
      network meta-analysis.
AB  - We completed a network meta-analysis of published papers to compare
      bisphosphonate gastrointestinal safety. We found that zoledronic acid had the
      highest chance of causing gastrointestinal adverse events. Etidronate had the
      highest chance of discontinuation due to an adverse event. No difference was
      found for serious adverse events. INTRODUCTION: Bisphosphonates are first-line
      treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the
      primary reason for non-adherence. Little is known about the comparative GI safety
      of bisphosphonates. PURPOSE: Leverage published clinical trial data to examine
      the comparative GI safety of bisphosphonates. METHODS: We completed a systematic
      review of all English-language clinical trials that assessed bisphosphonate
      safety and/or efficacy in primary osteoporosis through to 2012. Randomized,
      blinded, and controlled studies were eligible. The primary outcome was any GI
      related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea,
      esophageal-related events, and discontinuation due to AE. A Bayesian-based
      network meta-analysis was completed to allow for indirect comparisons. Results
      were reported as the probability that a specific drug had the highest number of
      events. RESULTS: We identified 50 studies: 32 alendronate, 12 risedronate, 5
      etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of
      having the highest number of any GI AE (91%) and nausea (70%). Etidronate (70%)
      and zoledronic acid (28%) had the highest probability of having the greatest
      attrition due to AE. Etidronate had the highest probability (56%) of having the
      greatest number of upper GI symptoms among oral bisphosphonates. CONCLUSION:
      Zoledronic acid had the highest probability of causing the greatest number of GI
      AE, possibly related to nausea. These results question the assumption that annual
      zoledronic acid will translate into better adherence. Little difference was found
      between alendronate and risedronate for serious AE. More research into real-world
      implications of the comparative safety of bisphosphonates is needed.

PMID- 24287511
TI  - The choroid plexus: a comprehensive review of its history, anatomy, function,
      histology, embryology, and surgical considerations.
AB  - INTRODUCTION: The role of the choroid plexus in cerebrospinal fluid production
      has been identified for more than a century. Over the years, more intensive
      studies of this structure has lead to a better understanding of the functions,
      including brain immunity, protection, absorption, and many others. Here, we
      review the macro- and microanatomical structure of the choroid plexus in addition
      to its function and embryology. METHOD: The literature was searched for articles
      and textbooks for data related to the history, anatomy, physiology, histology,
      embryology, potential functions, and surgical implications of the choroid plexus.
      All were gathered and summarized comprehensively. CONCLUSION: We summarize the
      literature regarding the choroid plexus and its surgical implications.

PMID- 24287513
TI  - How to deal with missing items in BASDAI and BASFI.

PMID- 24287514
TI  - The cartilage protein melanoma inhibitory activity contributes to inflammatory
      arthritis.
AB  - OBJECTIVE: Melanoma inhibitory activity (MIA) is a small chondrocyte-specific
      protein with unknown function. MIA knockout mice (MIA(-/-)) have a normal
      phenotype with minor microarchitectural alterations of cartilage. Our previous
      study demonstrated that immunodominant epitopes of MIA are actively presented in
      an HLA-DR4-restricted manner in the inflamed RA joint. The objective of this
      study was to investigate the potential role of MIA as an autoantigen. METHODS:
      Collagen-induced arthritis (CIA) and anti-collagen antibody-induced arthritis
      (CAIA) were induced in MIA(-/-) mice. Anti-type II collagen (anti-CII) antibodies
      were measured by ELISA. T cell proliferation and cytokine production were
      assessed by flow cytometry. RESULTS: MIA(-/-) mice had a markedly reduced
      incidence and severity of CIA and CAIA compared with wild-type (WT) mice.
      Attenuation of disease was not related to defective binding of anti-CII
      antibodies to cartilage in the absence of MIA. However, MIA(-/-) mice had
      significantly reduced anti-CII IgG1 and IgG2a antibody levels accompanied by an
      increase in FoxP3-expressing CD25(+)CD4(+) regulatory T cells. This was
      paralleled by a significant reduction in CII-specific IFN-gamma production by T
      cells in MIA(-/-) but not WT animals, suggesting a qualitative impact of MIA on
      the collagen-induced Th1 response. Furthermore, Ag-specific proliferation of T
      cells after restimulation with MIA in WT but not MIA(-/-) mice indicated the
      existence of MIA-specific T cells in the context of CIA. CONCLUSION: These data
      support a role for MIA as an autoantigen during arthritis development. Whether
      MIA can influence the balance of pathogenic vs regulatory responses in human RA
      remains to be investigated.

PMID- 24287515
TI  - Cerebrovascular accident (CVA) in association with a Taser-induced electrical
      injury.
AB  - Various adverse outcomes related to the use of electrical weapons such as the
      stun gun or the Taser have been described in the literature over the years.
      Examples include cardiac arrhythmias, blunt and penetrating injuries, seizure
      activity, and altered mental status. Imaging findings related to electrical
      injuries have become more frequent with advancing imaging technologies, such as
      CT or MRI. However, imaging findings and pathophysiology of electrical injuries
      that result in significant neurological events remain largely unexplored. We
      report the case of a patient who developed an ischemic stroke following Taser
      discharge, raising the possibility of association between the electrical injury
      and the ischemic stroke. 

PMID- 24287516
TI  - More than one non-canonical phosphodiester bond in the G-tract: formation of
      unusual parallel G-quadruplex structures.
AB  - In this article, we report an investigation, based on NMR and CD spectroscopic
      and electrophoretic techniques, of 5'TGGGGT3' analogues containing two or three
      3'-3' or 5'-5' inversion sites in the G-run, namely 5'TG3'-3'G5'-5'GGT3' (Q350),
      5'TG3'-3'GG5'-5'GT3' (Q305), 5'TGG3'-3'G5'-5'GT3' (Q035), 5'TG3'-3'G5'-5'G3'
      3'GT5' (Q353) and 3'TG5'-5'G3'-3'G5'-5'GT3' (Q535). Although the sequences
      investigated contain either no or only one natural 3'-5' linkage in the G-tract,
      all modified oligodeoxyribonucleotides (ODNs) have been shown to form stable
      tetramolecular quadruplex structures. The ability of the 3'-3' or 5'-5' inversion
      sites to affect the glycosidic conformation of guanosines and, consequently, base
      stacking, has also been investigated. The results of this study allow us to
      propose some generalizations concerning strand arrangements and the glycosidic
      conformational preference of residues adjacent to inverted polarity sites. These
      rules could be of general interest in the design of modified quadruplex
      structures, in view of their application as G-wires and modified aptamers. 

PMID- 24287525
TI  - Quality evaluation of agricultural distillates using an electronic nose.
AB  - The paper presents the application of an electronic nose instrument to fast
      evaluation of agricultural distillates differing in quality. The investigations
      were carried out using a prototype of electronic nose equipped with a set of six
      semiconductor sensors by FIGARO Co., an electronic circuit converting signal into
      digital form and a set of thermostats able to provide gradient temperature
      characteristics to a gas mixture. A volatile fraction of the agricultural
      distillate samples differing in quality was obtained by barbotage. Interpretation
      of the results involved three data analysis techniques: principal component
      analysis, single-linkage cluster analysis and cluster analysis with spheres
      method. The investigations prove the usefulness of the presented technique in the
      quality control of agricultural distillates. Optimum measurements conditions were
      also defined, including volumetric flow rate of carrier gas (15 L/h), thermostat
      temperature during the barbotage process (15  degrees C) and time of sensor
      signal acquisition from the onset of the barbotage process (60 s). 

PMID- 24287522
TI  - Microfluidic biosensor array with integrated poly(2,7-carbazole)/fullerene-based
      photodiodes for rapid multiplexed detection of pathogens.
AB  - A multiplexed microfluidic biosensor made of poly(methylmethacrylate) (PMMA) was
      integrated into an array of organic blend heterojunction photodiodes (OPDs) for
      chemiluminescent detection of pathogens. Waterborne Escherichia coli O157:H7,
      Campylobacter jejuni and adenovirus were targeted in the PMMA chip, and detection
      of captured pathogens was conducted by poly(2,7-carbazole)/fullerene OPDs which
      showed a responsivity over 0.20 A/W at 425 nm. The limits of chemiluminescent
      detection were 5 * 10(5) cells/mL for E. coli, 1 * 10(5) cells/mL for C. jejuni,
      and 1 * 10(-8) mg/mL for adenovirus. Parallel analysis for all three analytes in
      less than 35 min was demonstrated. Further recovery tests illustrated the
      potential of the integrated biosensor for detecting bacteria in real water
      samples.

PMID- 24287526
TI  - Detection of off-flavor in catfish using a conducting polymer electronic-nose
      technology.
AB  - The Aromascan A32S conducting polymer electronic nose was evaluated for the
      capability of detecting the presence of off-flavor malodorous compounds in
      catfish meat fillets to assess meat quality for potential merchantability. Sensor
      array outputs indicated that the aroma profiles of good-flavor (on-flavor) and
      off-flavor fillets were strongly different as confirmed by a Principal Component
      Analysis (PCA) and a Quality Factor value (QF > 7.9) indicating a significant
      difference at (P < 0.05). The A32S e-nose effectively discriminated between good
      flavor and off-flavor catfish at high levels of accuracy (>90%) and with
      relatively low rates (<=5%) of unknown or indecisive determinations in three
      trials. This A32S e-nose instrument also was capable of detecting the incidence
      of mild off-flavor in fillets at levels lower than the threshold of human
      olfactory detection. Potential applications of e-nose technologies for pre- and
      post-harvest management of production and meat-quality downgrade problems
      associated with catfish off-flavor are discussed. 

PMID- 24287529
TI  - Comparability of red/near-infrared reflectance and NDVI based on the spectral
      response function between MODIS and 30 other satellite sensors using rice canopy
      spectra.
AB  - Long-term monitoring of regional and global environment changes often depends on
      the combined use of multi-source sensor data. The most widely used vegetation
      index is the normalized difference vegetation index (NDVI), which is a function
      of the red and near-infrared (NIR) spectral bands. The reflectance and NDVI data
      sets derived from different satellite sensor systems will not be directly
      comparable due to different spectral response functions (SRF), which has been
      recognized as one of the most important sources of uncertainty in the multi
      sensor data analysis. This study quantified the influence of SRFs on the red and
      NIR reflectances and NDVI derived from 31 Earth observation satellite sensors.
      For this purpose, spectroradiometric measurements were performed for paddy rice
      grown under varied nitrogen levels and at different growth stages. The rice
      canopy reflectances were convoluted with the spectral response functions of
      various satellite instruments to simulate sensor-specific reflectances in the red
      and NIR channels. NDVI values were then calculated using the simulated red and
      NIR reflectances. The results showed that as compared to the Terra MODIS, the
      mean relative percentage difference (RPD) ranged from -12.67% to 36.30% for the
      red reflectance, -8.52% to -0.23% for the NIR reflectance, and -9.32% to 3.10%
      for the NDVI. The mean absolute percentage difference (APD) compared to the Terra
      MODIS ranged from 1.28% to 36.30% for the red reflectance, 0.84% to 8.71% for the
      NIR reflectance, and 0.59% to 9.32% for the NDVI. The lowest APD between MODIS
      and the other 30 satellite sensors was observed for Landsat5 TM for the red
      reflectance, CBERS02B CCD for the NIR reflectance and Landsat4 TM for the NDVI.
      In addition, the largest APD between MODIS and the other 30 satellite sensors was
      observed for IKONOS for the red reflectance, AVHRR1 onboard NOAA8 for the NIR
      reflectance and IKONOS for the NDVI. The results also indicated that AVHRRs
      onboard NOAA7-17 showed higher differences than did the other sensors with
      respect to MODIS. A series of optimum models were presented for remote sensing
      data assimilation between MODIS and other sensors. 

PMID- 24287531
TI  - Detection of illegal race walking: a tool to assist coaching and judging.
AB  - Current judging of race walking in international competitions relies on
      subjective human observation to detect illegal gait, which naturally has inherent
      problems. Incorrect judging decisions may devastate an athlete and possibly
      discredit the international governing body. The aim of this study was to
      determine whether an inertial sensor could improve accuracy, monitor every step
      the athlete makes in training and/or competition. Seven nationally competitive
      race walkers performed a series of legal, illegal and self-selected pace races.
      During testing, athletes wore a single inertial sensor (100 Hz) placed at S1 of
      the vertebra and were simultaneously filmed using a high-speed camera (125 Hz).
      Of the 80 steps analyzed the high-speed camera identified 57 as illegal, the
      inertial sensor misidentified four of these measures (all four missed illegal
      steps had 0.008 s of loss of ground contact) which is considerably less than the
      best possible human observation of 0.06 s. Inertial sensor comparison to the
      camera found the typical error of estimate was 0.02 s (95% confidence limits 0.01
      0.02), with a bias of 0.02 (+/-0.01). An inertial sensor can thus objectively
      improve the accuracy in detecting illegal steps (loss of ground contact) and,
      along with the ability to monitor every step of the athlete, could be a valuable
      tool to assist judges during race walk events. 

PMID- 24287532
TI  - A label-free microfluidic biosensor for activity detection of single microalgae
      cells based on chlorophyll fluorescence.
AB  - Detection of living microalgae cells is very important for ballast water
      treatment and analysis. Chlorophyll fluorescence is an indicator of
      photosynthetic activity and hence the living status of plant cells. In this
      paper, we developed a novel microfluidic biosensor system that can quickly and
      accurately detect the viability of single microalgae cells based on chlorophyll
      fluorescence. The system is composed of a laser diode as an excitation light
      source, a photodiode detector, a signal analysis circuit, and a microfluidic chip
      as a microalgae cell transportation platform. To demonstrate the utility of this
      system, six different living and dead algae samples (Karenia mikimotoi Hansen,
      Chlorella vulgaris, Nitzschia closterium, Platymonas subcordiformis,
      Pyramidomonas delicatula and Dunaliella salina) were tested. The developed
      biosensor can distinguish clearly between the living microalgae cells and the
      dead microalgae cells. The smallest microalgae cells that can be detected by
      using this biosensor are 3 MUm ones. Even smaller microalgae cells could be
      detected by increasing the excitation light power. The developed microfluidic
      biosensor has great potential for in situ ballast water analysis. 

PMID- 24287533
TI  - A wireless MEMS-based inclinometer sensor node for structural health monitoring.
AB  - This paper proposes a wireless inclinometer sensor node for structural health
      monitoring (SHM) that can be applied to civil engineering and building structures
      subjected to various loadings. The inclinometer used in this study employs a
      method for calculating the tilt based on the difference between the static
      acceleration and the acceleration due to gravity, using a micro-electro
      mechanical system (MEMS)-based accelerometer. A wireless sensor node was
      developed through which tilt measurement data are wirelessly transmitted to a
      monitoring server. This node consists of a slave node that uses a short-distance
      wireless communication system (RF 2.4 GHz) and a master node that uses a long
      distance telecommunication system (code division multiple access-CDMA). The
      communication distance limitation, which is recognized as an important issue in
      wireless monitoring systems, has been resolved via these two wireless
      communication components. The reliability of the proposed wireless inclinometer
      sensor node was verified experimentally by comparing the values measured by the
      inclinometer and subsequently transferred to the monitoring server via wired and
      wireless transfer methods to permit a performance evaluation of the wireless
      communication sensor nodes. The experimental results indicated that the two
      systems (wired and wireless transfer systems) yielded almost identical values at
      a tilt angle greater than 1 degrees , and a uniform difference was observed at a
      tilt angle less than 0.42 degrees  (approximately 0.0032 degrees  corresponding
      to 0.76% of the tilt angle, 0.42 degrees ) regardless of the tilt size. This
      result was deemed to be within the allowable range of measurement error in SHM.
      Thus, the wireless transfer system proposed in this study was experimentally
      verified for practical application in a structural health monitoring system. 

PMID- 24287535
TI  - Impedimetric aptasensor for ochratoxin A determination based on Au nanoparticles
      stabilized with hyper-branched polymer.
AB  - An impedimetric aptasensor for ochratoxin A (OTA) detection has been developed on
      the base of a gold electrode covered with a new modifier consisting of
      electropolymerized Neutral Red and a mixture of Au nanoparticles suspended in the
      dendrimeric polymer Botlorn H30(r). Thiolated aptamer specific to OTA was
      covalently attached to Au nanoparticles via Au-S bonding. The interaction of the
      aptamer with OTA induced the conformational switch of the aptamer from linear to
      guanine quadruplex form followed by consolidation of the surface layer and an
      increase of the charge transfer resistance. The aptasensor makes it possible to
      detect from 0.1 to 100 nM of OTA (limit of detection: 0.02 nM) in the presence of
      at least 50 fold excess of ochratoxin B. The applicability of the aptasensor for
      real sample assay was confirmed by testing spiked beer samples. The recovery of 2
      nM OTA was found to be 70% for light beer and 78% for dark beer. 

PMID- 24287538
TI  - Assessing the potential of low-cost 3D cameras for the rapid measurement of plant
      woody structure.
AB  - Detailed 3D plant architectural data have numerous applications in plant science,
      but many existing approaches for 3D data collection are time-consuming and/or
      require costly equipment. Recently, there has been rapid growth in the
      availability of low-cost, 3D cameras and related open source software
      applications. 3D cameras may provide measurements of key components of plant
      architecture such as stem diameters and lengths, however, few tests of 3D cameras
      for the measurement of plant architecture have been conducted. Here, we measured
      Salix branch segments ranging from 2-13 mm in diameter with an Asus Xtion camera
      to quantify the limits and accuracy of branch diameter measurement with a 3D
      camera. By scanning at a variety of distances we also quantified the effect of
      scanning distance. In addition, we also test the sensitivity of the program KinFu
      for continuous 3D object scanning and modeling as well as other similar software
      to accurately record stem diameters and capture plant form (<3 m in height).
      Given its ability to accurately capture the diameter of branches >6 mm, Asus
      Xtion may provide a novel method for the collection of 3D data on the branching
      architecture of woody plants. Improvements in camera measurement accuracy and
      available software are likely to further improve the utility of 3D cameras for
      plant sciences in the future. 

PMID- 24287536
TI  - Multi-wave and hybrid imaging techniques: a new direction for nondestructive
      testing and structural health monitoring.
AB  - In this article, the state-of-the-art multi-wave and hybrid imaging techniques in
      the field of nondestructive evaluation and structural health monitoring were
      comprehensively reviewed. A new direction for assessment and health monitoring of
      various structures by capitalizing the advantages of those imaging methods was
      discussed. Although sharing similar system configurations, the imaging physics
      and principles of multi-wave phenomena and hybrid imaging methods are inherently
      different. After a brief introduction of nondestructive evaluation (NDE) ,
      structure health monitoring (SHM) and their related challenges, several recent
      advances that have significantly extended imaging methods from laboratory
      development into practical applications were summarized, followed by conclusions
      and discussion on future directions. 

PMID- 24287539
TI  - Electrochemical determination of glycoalkaloids using a carbon nanotubes
      phenylboronic acid modified glassy carbon electrode.
AB  - A versatile strategy for electrochemical determination of glycoalkaloids (GAs)
      was developed by using a carbon nanotubes-phenylboronic acid (CNTs-PBA) modified
      glassy carbon electrode. PBA reacts with alpha-solanine and alpha-chaconine to
      form a cyclic ester, which could be utilized to detect GAs. This method allowed
      GA detection from 1 MUM to 28 MUM and the detection limit was 0.3 MUM. Affinity
      interaction of GAs and immobilized PBA caused an essential change of the peak
      current. The CNT-PBA modified electrodes were sensitive for detection of GAs, and
      the peak current values were in quite good agreement with those measured by the
      sensors. 

PMID- 24287540
TI  - Software Defined Radio (SDR) and Direct Digital Synthesizer (DDS) for NMR/MRI
      instruments at low-field.
AB  - A proof-of-concept of the use of a fully digital radiofrequency (RF) electronics
      for the design of dedicated Nuclear Magnetic Resonance (NMR) systems at low-field
      (0.1 T) is presented. This digital electronics is based on the use of three key
      elements: a Direct Digital Synthesizer (DDS) for pulse generation, a Software
      Defined Radio (SDR) for a digital receiving of NMR signals and a Digital Signal
      Processor (DSP) for system control and for the generation of the gradient signals
      (pulse programmer). The SDR includes a direct analog-to-digital conversion and a
      Digital Down Conversion (digital quadrature demodulation, decimation filtering,
      processing gain...). The various aspects of the concept and of the realization
      are addressed with some details. These include both hardware design and software
      considerations. One of the underlying ideas is to enable such NMR systems to
      "enjoy" from existing advanced technology that have been realized in other
      research areas, especially in telecommunication domain. Another goal is to make
      these systems easy to build and replicate so as to help research groups in
      realizing dedicated NMR desktops for a large palette of new applications. We also
      would like to give readers an idea of the current trends in this field. The
      performances of the developed electronics are discussed throughout the paper.
      First FID (Free Induction Decay) signals are also presented. Some development
      perspectives of our work in the area of low-field NMR/MRI will be finally
      addressed. 

PMID- 24287541
TI  - Proximal gamma-ray spectroscopy to predict soil properties using windows and full
      spectrum analysis methods.
AB  - Fine-scale spatial information on soil properties is needed to successfully
      implement precision agriculture. Proximal gamma-ray spectroscopy has recently
      emerged as a promising tool to collect fine-scale soil information. The objective
      of this study was to evaluate a proximal gamma-ray spectrometer to predict
      several soil properties using energy-windows and full-spectrum analysis methods
      in two differently managed sandy loam fields: conventional and organic. In the
      conventional field, both methods predicted clay, pH and total nitrogen with a
      good accuracy (R2 >= 0.56) in the top 0-15 cm soil depth, whereas in the organic
      field, only clay content was predicted with such accuracy. The highest prediction
      accuracy was found for total nitrogen (R2 = 0.75) in the conventional field in
      the energy-windows method. Predictions were better in the top 0-15 cm soil depths
      than in the 15-30 cm soil depths for individual and combined fields. This implies
      that gamma-ray spectroscopy can generally benefit soil characterisation for
      annual crops where the condition of the seedbed is important. Small differences
      in soil structure (conventional vs. organic) cannot be determined. As for the
      methodology, we conclude that the energy-windows method can establish relations
      between radionuclide data and soil properties as accurate as the full-spectrum
      analysis method. 

PMID- 24287543
TI  - Aptamer-based analysis: a promising alternative for food safety control.
AB  - Ensuring food safety is nowadays a top priority of authorities and professional
      players in the food supply chain. One of the key challenges to determine the
      safety of food and guarantee a high level of consumer protection is the
      availability of fast, sensitive and reliable analytical methods to identify
      specific hazards associated to food before they become a health problem. The
      limitations of existing methods have encouraged the development of new
      technologies, among them biosensors. Success in biosensor design depends largely
      on the development of novel receptors with enhanced affinity to the target, while
      being stable and economical. Aptamers fulfill these characteristics, and thus
      have surfaced as promising alternatives to natural receptors. This Review
      describes analytical strategies developed so far using aptamers for the control
      of pathogens, allergens, adulterants, toxins and other forbidden contaminants to
      ensure food safety. The main progresses to date are presented, highlighting
      potential prospects for the future. 

PMID- 24287544
TI  - New beta-cyclodextrin entrapped in polyethyleneimine film-modified electrodes for
      pharmaceutical compounds determination.
AB  - The electrochemical behavior of ascorbic acid and uric acid on glassy carbon bare
      electrodes and ones modified with beta-cyclodextrin entrapped in
      polyethyleneimine film has been investigated using square wave voltammetry. The
      electrode modification was achieved in order to separate the voltammetric peaks
      of ascorbic acid and uric acid when present in the same solution. On the modified
      electrodes the potential of the oxidation peak of the ascorbic acid was shifted
      to more negative values by over 0.3 V, while in the case of uric acid, the
      negative potential shift was about 0.15 V compared to the bare glassy carbon
      electrode. When the two compounds were found together in the solution, on the
      bare electrode only a single broad signal was observed, while on the modified
      electrode the peak potentials of these two compounds were separated by 0.4 V.
      When the uric acid concentration remained constant, the peak intensity of the
      ascorbic acid is increased linearly with the concentration (r2 = 0.996) and when
      the ascorbic acid concentration remains constant, the peak intensity of the uric
      acid increased linearly with the concentration (r2 = 0.992). FTIR measurements
      supported the formation of inclusion complexes. In order to characterize the
      modification of the electrodes microscopic studies were performed. The modified
      electrodes were successfully employed for the determination of ascorbic acid in
      pharmaceutical formulations with a detection limit of 0.22 uM. 

PMID- 24287545
TI  - Noninvasive high-throughput single-cell analysis of HIV protease activity using
      ratiometric flow cytometry.
AB  - To effectively fight against the human immunodeficiency virus infection/ acquired
      immunodeficiency syndrome (HIV/AIDS) epidemic, ongoing development of novel HIV
      protease inhibitors is required. Inexpensive high-throughput screening assays are
      needed to quickly scan large sets of chemicals for potential inhibitors. We have
      developed a Forster resonance energy transfer (FRET)-based, HIV protease
      sensitive sensor using a combination of a fluorescent protein pair, namely
      mCerulean and mCitrine. Through extensive in vitro characterization, we show that
      the FRET-HIV sensor can be used in HIV protease screening assays. Furthermore, we
      have used the FRET-HIV sensor for intracellular quantitative detection of HIV
      protease activity in living cells, which more closely resembles an actual viral
      infection than an in vitro assay. We have developed a high-throughput method that
      employs a ratiometric flow cytometry for analyzing large populations of cells
      that express the FRET-HIV sensor. The method enables FRET measurement of single
      cells with high sensitivity and speed and should be used when subpopulation
      specific intracellular activity of HIV protease needs to be estimated. In
      addition, we have used a confocal microscopy sensitized emission FRET technique
      to evaluate the usefulness of the FRET-HIV sensor for spatiotemporal detection of
      intracellular HIV protease activity. 

PMID- 24287546
TI  - A table-shaped tactile sensor for detecting triaxial force on the basis of strain
      distribution.
AB  - A slim and flexible tactile sensor applicable to the interaction of human and
      intelligent robots is presented. In particular, a simple sensing principle for
      decoupling of three-dimensional force is proposed. Sensitivity of the proposed
      tactile sensor is tested experimentally. To improve the sensitivity of the
      sensor, a table-shaped sensing element was designed. Table-shaped structure can
      convert an external acting force into concentrated internal stress. A "triaxial
      force decoupling algorithm" was developed by combining two-dimensional mapping
      data calculated by finite element analysis. The sensor was calibrated under
      normal and tangential forces. The external loads applied to the sensor could be
      decoupled independently as a function of the strain-gauge responses. 

PMID- 24287549
TI  - Detection of pulmonary amylase activity in exhaled breath condensate.
AB  - Amylase activity in exhaled breath condensate (EBC) is usually interpreted as an
      indication of oropharyngeal contamination despite the fact that amylase can be
      found in pulmonary excretions. The aim of this study was to recruit and refine an
      amylase assay in order to detect amylase activity in any EBC sample and to
      develop a method to identify EBC samples containing amylase of pulmonary origin.
      EBC was collected from 40 volunteers with an EcoScreen condenser. Amylase assays
      and methods to discriminate between oropharyngeal and pulmonary proteins were
      tested and developed using matched EBC and saliva samples. Our refined 2-chloro-4
      nitrophenyl-alpha-D-maltotriosid (CNP-G3) assay was 40-fold more sensitive than
      the most sensitive commercial assay and allowed detection of amylase activity in
      30 ul of EBC. We developed a dot-blot assay which allowed detection of salivary
      protein in saliva diluted up to 150 000-fold. By plotting amylase activity
      against staining intensity we identified a few EBC samples with high amylase
      activity which were aligned with diluted saliva. We believe that EBC samples
      aligned with diluted saliva contain amylase activity introduced during EBC
      collection and that all other EBC samples contain amylase activity of pulmonary
      origin and are basically free of oropharyngeal protein contamination. 

PMID- 24287550
TI  - Repeating pattern of non-RVD variations in DNA-binding modules enhances TALEN
      activity.
AB  - Transcription activator-like effector (TALE) nuclease (TALEN) is a site-specific
      nuclease, which can be freely designed and easily constructed. Numerous methods
      of constructing TALENs harboring different TALE scaffolds and repeat variants
      have recently been reported. However, the functionalities of structurally
      different TALENs have not yet been compared. Here, we report on the functional
      differences among several types of TALENs targeting the same loci. Using HEK293T
      cell-based single-strand annealing and Cel-I nuclease assays, we found that
      TALENs with periodically-patterned repeat variants harboring non-repeat-variable
      di-residue (non-RVD) variations (Platinum TALENs) showed higher activities than
      TALENs without non-RVD variations. Furthermore, the efficiencies of gene
      disruption mediated by Platinum TALENs in frogs and rats were significantly
      higher than in previous reports. This study therefore demonstrated an efficient
      system for the construction of these highly active Platinum TALENs (Platinum Gate
      system), which could establish a new standard in TALEN engineering. 

PMID- 24287551
TI  - Structural insights into how 5-hydroxymethylation influences transcription factor
      binding.
AB  - Transcription factor binding and high resolution crystallographic studies (1.3 A)
      of Dickerson-Drew duplexes with cytosine, methylcytosine and
      hydroxymethylcytosine bases provide evidence that C-5 cytosine modifications
      could regulate transcription by context dependent effects on DNA transcription
      factor interactions. 

PMID- 24287553
TI  - Zinc to cadmium replacement in the prokaryotic zinc-finger domain.
AB  - Given the similar chemical properties of zinc and cadmium, zinc finger domains
      have been often proposed as mediators of the toxic and carcinogenic effects
      exerted by this xenobiotic metal. The effects of zinc replacement by cadmium in
      different eukaryotic zinc fingers have been reported. In the present work, to
      evaluate the effects of such substitution in the prokaryotic zinc finger, we
      report a detailed study of its functional and structural consequences on the Ros
      DNA binding domain (Ros87). We show that this protein, which bears important
      structural differences with respect to the eukaryotic domains, appears to
      structurally tolerate the zinc to cadmium substitution and the presence of
      cadmium does not affect the DNA binding activity of the protein. Moreover, we
      show for the first time how zinc to cadmium replacement can also take place in a
      cellular context. Our findings both complement and extend previous results
      obtained for different eukaryotic zinc fingers, suggesting that metal
      substitution in zinc fingers may be of relevance to the toxicity and/or
      carcinogenicity mechanisms of this metal. 

PMID- 24287554
TI  - Experimental recovery of quantum correlations in absence of system-environment
      back-action.
AB  - Revivals of quantum correlations in composite open quantum systems are a useful
      dynamical feature against detrimental effects of the environment. Their
      occurrence is attributed to flows of quantum information back and forth from
      systems to quantum environments. However, revivals also show up in models where
      the environment is classical, thus unable to store quantum correlations, and
      forbids system-environment back-action. This phenomenon opens basic issues about
      its interpretation involving the role of classical environments, memory effects,
      collective effects and system-environment correlations. Moreover, an experimental
      realization of back-action-free quantum revivals has applicative relevance as it
      leads to recover quantum resources without resorting to more demanding structured
      environments and correction procedures. Here we introduce a simple two-qubit
      model suitable to address these issues. We then report an all-optical experiment
      which simulates the model and permits us to recover and control, against
      decoherence, quantum correlations without back-action. We finally give an
      interpretation of the phenomenon by establishing the roles of the involved
      parties. 

PMID- 24287552
TI  - Taste bud homeostasis in health, disease, and aging.
AB  - The mammalian taste bud is an onion-shaped epithelial structure with 50-100
      tightly packed cells, including taste receptor cells, supporting cells, and basal
      cells. Taste receptor cells detect nutrients and toxins in the oral cavity and
      transmit the sensory information to gustatory nerve endings in the buds.
      Supporting cells may play a role in the clearance of excess neurotransmitters
      after their release from taste receptor cells. Basal cells are precursor cells
      that differentiate into mature taste cells. Similar to other epithelial cells,
      taste cells turn over continuously, with an average life span of about 8-12 days.
      To maintain structural homeostasis in taste buds, new cells are generated to
      replace dying cells. Several recent studies using genetic lineage tracing methods
      have identified populations of progenitor/stem cells for taste buds, although
      contributions of these progenitor/stem cell populations to taste bud homeostasis
      have yet to be fully determined. Some regulatory factors of taste cell
      differentiation and degeneration have been identified, but our understanding of
      these aspects of taste bud homoeostasis remains limited. Many patients with
      various diseases develop taste disorders, including taste loss and taste
      distortion. Decline in taste function also occurs during aging. Recent studies
      suggest that disruption or alteration of taste bud homeostasis may contribute to
      taste dysfunction associated with disease and aging. 

PMID- 24287555
TI  - Palladium-103 plaque radiation therapy for American Joint Committee on cancer T3-
      and T4-staged choroidal melanomas.
AB  - IMPORTANCE: Patients with larger choroidal melanomas are being treated with
      plaque radiation therapy. OBJECTIVE: To report the methods and results of
      palladium-103 brachytherapy for American Joint Committee on Cancer, 7th edition,
      T3- and T4-sized choroidal melanomas. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis of the results of a clinical case series over a 10-year
      period of 47 consecutive patients with uveal melanoma. The patients were treated
      at The New York Eye Cancer Center, Beth Israel Comprehensive Cancer Center, or
      The New York Eye and Ear Infirmary between 2002 and 2012 and had a minimum follow
      up of 6 months. Tumors had a mean preoperative apical tumor height of 8.6 mm and
      a mean largest basal diameter of 15.8 mm. MAIN OUTCOMES AND MEASURES: We
      analyzed, but were not limited to, data on the methods of radiation therapy,
      local tumor control, adverse effects, vision retention, and metastatic rate.
      RESULTS: All patients completed therapy and received the prescribed tumor apex
      dose. At a median of 47 months (range, 6-125 months), the rate of local control
      was 91% and the rate of eye retention was 89%. The most common long-term
      brachytherapy-related complication was radiation maculopathy (66% of patients),
      followed by radiation optic neuropathy (51% of patients). One or both of these
      complications were diagnosed at a mean time of 16 months (range, 2-36 months)
      after brachytherapy. Secondary cataract developed in 36% of patients. Glaucoma
      developed in 17% of patients and resulted in enucleation in 4% of patients. The
      mean pretreatment visual acuity was 20/50 (range, 20/12.5 to hand motions), which
      evolved to a mean visual acuity of 20/100 (range, 20/20 to no light perception).
      Overall, 25 of 47 patients (53%) maintained 20/200 or better vision. Metastatic
      melanoma developed in 32% of patients. CONCLUSIONS AND RELEVANCE: Palladium-103
      ophthalmic plaque radiation therapy can be used as an eye- and vision-preserving
      treatment for relatively large American Joint Committee on Cancer T3- or T4-sized
      choroidal melanomas.

PMID- 24287556
TI  - Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses.
AB  - A library of hydrazide derivatives was synthesized to target non-structural
      protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug
      leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2
      yl)ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was
      identified by its ability to increase the melting temperature of the effector
      domain (ED) of the NS1 protein, as assayed using differential scanning
      fluorimetry. A library of HENC analogs was tested for inhibitory effect against
      influenza A virus replication in MDCK cells. A systematic diversification of HENC
      revealed the identity of the R group attached to the imine carbon atom
      significantly influenced the antiviral activity. A phenyl or cyclohexyl at this
      position yielded the most potent antiviral activity. The phenyl containing
      compound had antiviral activity similar to that of the active form of oseltamivir
      (Tamiflu), and had no detectable effect on cell viability. 

PMID- 24287557
TI  - Studies on the synthetic and structural aspects of benzosuberones bearing 2, 4
      thiazolidenone moiety as potential anti-cancer agents.
AB  - Novel representative of the important group of biologically active benzosuberones
      bearing 2, 4-thiazolidenone moiety was synthesized as potential anticancer agents
      (6a-j). These compounds were synthesized in good yields from Knoevenagel
      condensation of compounds 2a-b with thiazolidenone derivatives 3a-e in the
      presence of sodium acetate and glacial acetic acid. The in vitro cytotoxicity of
      these compounds was evaluated against different human cancer cell lines (A549,
      HeLa, MDA-MB-231, MCF-7) and normal cell line, HEK293. Compound 6a exhibited
      promising cytotoxicity with IC50 values ranging from 2.98 to 13.34 MUM against
      all the tested cancer cell lines, HeLa, A549, MCF-7 and MDA-MB-231, while
      compound 6g showed potent cytotoxicity against human breast adenocarcinoma cell
      line (MCF-7, IC50 value of 1.91 MUM).

PMID- 24287558
TI  - Synthesis and analysis of activity of a potential anti-melanoma prodrug with a
      hydrazine linker.
AB  - A potential anti-melanoma prodrug containing a phenolic activator, a hydrazine
      linker, and a nitrogen mustard effector - (N-{4-[bis-(2
      chloroethyl)amino]benzoyl}-N'-(4-hydroxybenzyl)hydrazine) has been synthesized in
      seven steps. Spectrophotometric measurements of its oxidation by tyrosinase
      showed a rapid increase of absorbance at 337 nm. HPLC analysis demonstrated that
      two major products were formed. However, during the reaction one of the products
      was converted into the other. The stable product with a maximum of absorption at
      337 nm was isolated and identified as 5,6-dihydroxy-1H-indazol-1-yl 4-[bis-(2
      chloroethyl)amino]benzoate. It was formed by a cyclization of the enzymatically
      generated o-quinone. This reaction was unexpected, since the acylated hydrazine
      nitrogen atom should not be sufficiently nucleophilic to attack the o-quinone
      ring. This cyclization prevented the effector release from the enzyme-activated
      prodrug. As a result, the prodrug showed only limited specificity for B16-F10
      murine melanoma cells compared to reference cell lines. When applied in solid
      tumors in mice it showed slightly higher activity than the parent mustard drug (4
      [bis-(2-chloroethyl)amino]benzoic cid), but significantly lower activity than
      melphalan, a commercial mustard drug with a structure resembling tyrosine,
      occasionally used in the treatment of melanoma.

PMID- 24287559
TI  - Structure-based screening for the discovery of new carbonic anhydrase VII
      inhibitors.
AB  - Among the different mammalian isoforms of Carbonic Anhydrase, the hCA VII is
      mainly expressed in the brain where it is involved in several neurological
      diseases. Thereby hCA VII has been validated as an attractive target for the
      discovery of selective inhibitors for the treatment of epilepsy and neurological
      pain. To identify new chemical entities as carbonic anhydrase inhibitors (CAIs)
      targeting hCA VII, we used a structure-based approach. By means of LigandScout
      software we built pharmacophore models from crystal structures of two well-known
      CAIs in complex with hCA VII. A merged pharmacophore hypothesis has been
      obtained. Subsequently, a focused library of compounds was screened against
      pharmacophore model and the most interesting hits were docked into the crystal
      structure of hCA VII. As a result, we identified new compounds displaying
      significant CA inhibitory effects in the nanomolar range. 

PMID- 24287560
TI  - Synthesis, biological activity and structure-activity relationships of new
      benzoic acid-based protein tyrosine phosphatase inhibitors endowed with
      insulinomimetic effects in mouse C2C12 skeletal muscle cells.
AB  - Insulin resistance is a complex altered metabolic condition characterized by
      impaired insulin signaling and implicated in the pathogenesis of serious human
      diseases, such as diabetes, obesity, neurodegenerative pathologies. In pursuing
      our aim to identify new agents able to improve cellular insulin sensitivity, we
      have synthesized new 4-[(5-arylidene-4-oxo-2-phenylimino/oxothiazolidin-3
      yl)methyl]benzoic acids (5, 8) and evaluated their inhibitory activity towards
      human protein tyrosine phosphatases PTP1B, LMW-PTP and TCPTP, enzymes which are
      involved in the development of insulin resistance. Compounds 5 and 8 showed from
      moderate to significant selectivity toward PTP1B over both the highly homologous
      TCPTP and the two isoforms of human LMW-PTP. In addition, most of the tested
      compounds selectively inhibited LMW-PTP IF1 over the isoform IF2. Docking studies
      into the active sites of PTP1B and LMW-PTP aided the rationalization of the
      observed PTP inhibitory profile. Moreover, most tested compounds were capable to
      induce the insulin metabolic pathway in mouse C2C12 skeletal muscle cells by
      remarkably stimulating both IRbeta phosphorylation and 2-deoxyglucose cellular
      uptake. 

PMID- 24287561
TI  - Urea/oxalamide tethered beta-lactam-7-chloroquinoline conjugates: synthesis and
      in vitro antimalarial evaluation.
AB  - The manuscript pertains to the synthesis of urea/oxalamide tethered beta-lactam-7
      chloroquinoline conjugates with well modulated chain lengths and their
      antimalarial evaluation. The results reveal the dependence of activity profiles
      on the N-1 substituent of the beta-lactam ring, the nature of the linker as well
      as the length of the alkyl chain. The most potent of the tested compounds showed
      an IC50 of 34.97 nM against chloroquine resistant W2 strain of Plasmodium
      falciparum.

PMID- 24287562
TI  - The thermodynamics of the self-assembly of covalently linked oligomeric
      naphthalenediimides into helical organic nanotubes.
AB  - The mechanism and thermodynamic functions of the self-assembly of a family of
      covalently linked oligomeric naphthalenediimides (NDIs) were investigated through
      variable-temperature NMR and CD studies. The NDIs were shown to self-assemble
      into helical supramolecular nanotubes via an isodesmic polymerisation mechanism,
      and regardless of the oligomer length a surprising entropy-enthalpy compensation
      was observed. 

PMID- 24287563
TI  - DHEA inhibits vascular remodeling following arterial injury: a possible role in
      suppression of inflammation and oxidative stress derived from vascular smooth
      muscle cells.
AB  - Vascular remodeling is characterized by the aggregation of vascular smooth muscle
      cells (VSMCs) in intima. Previous studies have demonstrated that
      dehydroepiandrosterone (DHEA), a steroid hormone, can reverse vascular
      remodeling. However, it is still far clear that whether and how DHEA participates
      in the modulation of VSMCs activation and vascular remodeling. VSMCs were
      obtained from the thoracic aorta of SD rats. Cell proliferation was evaluated by
      CCK-8 assay and BrdU assay. To measure VSMCs migration activity, a transwell
      chamber assay was performed. Quantitative real-time RT-PCR and western blot were
      used to explore the molecular mechanisms. ROS generation by VSMCs was measured by
      DCF fluorescence. NADPH oxidase activity and SOD activity were measured by the
      corresponding kits. NF-kappaB activity was detected by NF-kappaB luciferase
      reporter gene assay. A rat carotid artery balloon injury model was built to
      evaluate the neointimal formation, and plasma PGF2 was measured by ELISA. Our
      results showed that DHEA significantly inhibited VSMCs proliferation after
      angiotensin (Ang II) stimulation by down-regulation of NADPH oxidase activity and
      ERK1/2 phosphorylation. Ang II can increase IL-6 and MCP-1 expression, but DHEA
      reverses these changes via inhibiting p38-MAPK/NF-kappaB (p65) signaling pathway.
      DHEA has no significant effects on VSMCs phenotype transition, but can reduce the
      neointimal to media area ratio after balloon injury. DHEA can alleviate oxidative
      stress and inflammation in VSMCs via ERK1/2 and NF-kappaB signaling pathway, but
      has no effect on VSMCs phenotype transition. Furthermore, DHEA attenuates VSMCs
      activation and neointimal formation after carotid injury in vivo. Taken together,
      DHEA might be a promising treatment for vascular injury under pathological
      condition. 

PMID- 24287564
TI  - The action of p-synephrine on hepatic carbohydrate metabolism and respiration
      occurs via both Ca(2+)-mobilization and cAMP production.
AB  - Citrus aurantium extracts, which contain large amounts of p-synephrine, are
      widely used for weight loss purposes and as appetite suppressants. In the liver,
      C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate
      metabolism, and oxygen uptake. The purpose of the present work was to quantify
      the action of p-synephrine and also to obtain indications about its mechanism of
      action, a task that would be difficult to accomplish with C. aurantium extracts
      due to their rather complex composition. The experimental system was the isolated
      perfused rat liver. p-Synephrine significantly stimulated glycogenolysis,
      glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the
      portal perfusion pressure and the redox state of the cytosolic NAD(+)/NADH
      couple. A Ca(2+)-dependency for both the hemodynamic and the metabolic effects of
      p-synephrine was found. p-Synephrine stimulated both cAMP overflow and the
      initial Ca(2+) release from the cellular stores previously labeled with
      (45)Ca(2+). The metabolic and hemodynamic actions of p-synephrine were strongly
      inhibited by alpha-adrenergic antagonists and moderately affected by beta
      adrenergic antagonists. The results allow to conclude that p-synephrine presents
      important metabolic and hemodynamic effects in the liver. These effects can be
      considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis),
      they are mediated by both alpha- and beta-adrenergic signaling, require the
      simultaneous participation of both Ca(2+) and cAMP, and could be contributing to
      the overall stimulation of metabolism that usually occurs during weight loss
      periods. 

PMID- 24287565
TI  - miR-124 functions as a tumor suppressor in the endometrial carcinoma cell line
      HEC-1B partly by suppressing STAT3.
AB  - MicroRNAs (miRNAs) play an important role in the development and progression of
      endometrial carcinoma (EC). Recently, several studies have shown that microRNA
      124 (miR-124) is downregulated in various cancers, which can affect tumor
      initiation and maintenance. However, the effects of miR-124 on EC are largely
      unknown. In this study, we identified the under-expression of miR-124 in 35
      paired EC tissues and adjacent normal tissues. Further, functional experiments
      found that ectopic expression of miR-124 markedly suppressed cell proliferation,
      migration, and invasion of EC cells. It also induced cell apoptosis and G1-phase
      cell cycle arrest. Moreover, we identified signal transducer and activator of
      transcription 3 (STAT3) as a direct target of miR-124, and over expression of miR
      124 not only induced changes in STAT3 expression but also altered expression of
      its target genes, cyclin D2 and matrix metalloproteinase 2, in the human
      endometrial carcinoma cell line HEC-1B. In addition to targeting STAT3 directly,
      we found that miR-124 suppresses phosphorylation of STAT3 through targeting IL-6R
      indirectly. Restored STAT3 expression through treatment with IL-6 cytokine partly
      abolished miR-124-mediated cell cycle arrest and apoptosis induction. These
      results combined with the tumorigenetic role of STAT3 in HEC-1B cells suggest
      that the antitumor effects of miR-124 are achieved, at least partly, through down
      regulation of STAT3 mRNA and its downstream target genes. Therefore, inhibition
      of constitutively activated STAT3 by ectopic expression of miR-124 in EC may
      provide a novel therapeutic strategy for the treatment of EC. 

PMID- 24287566
TI  - Kinetics of CH2OO reactions with SO2, NO2, NO, H2O and CH3CHO as a function of
      pressure.
AB  - Kinetics of CH2OO Criegee intermediate reactions with SO2, NO2, NO, H2O and
      CH3CHO and CH2I radical reactions with NO2 are reported as a function of pressure
      at 295 K. Measurements were made under pseudo-first-order conditions using flash
      photolysis of CH2I2-O2-N2 gas mixtures in the presence of excess co-reagent
      combined with monitoring of HCHO reaction products by laser-induced fluorescence
      (LIF) spectroscopy and, for the reaction with SO2, direct detection of CH2OO by
      photoionisation mass spectrometry (PIMS). Rate coefficients for CH2OO + SO2 and
      CH2OO + NO2 are independent of pressure in the ranges studied and are (3.42 +/-
      0.42) * 10(-11) cm(3) s(-1) (measured between 1.5 and 450 Torr) and (1.5 +/- 0.5)
      * 10(-12) cm(3) s(-1) (measured between 25 and 300 Torr), respectively. The rate
      coefficient for CH2OO + CH3CHO is pressure dependent, with the yield of HCHO
      decreasing with increasing pressure. Upper limits of 2 * 10(-13) cm(3) s(-1) and
      9 * 10(-17) cm(3) s(-1) are placed on the rate coefficients for CH2OO + NO and
      CH2OO + H2O, respectively. The upper limit for the rate coefficient for CH2OO +
      H2O is significantly lower than has been reported previously, with consequences
      for modelling of atmospheric impacts of CH2OO chemistry. 

PMID- 24287567
TI  - Mitochondrial inner membrane protease promotes assembly of presequence
      translocase by removing a carboxy-terminal targeting sequence.
AB  - The presequence translocase of the inner mitochondrial membrane (TIM23 complex)
      is essential for importing cleavable preproteins into mitochondria. The
      preproteins contain amino-terminal targeting sequences that are removed by the
      mitochondrial processing peptidase (MPP). Some preproteins carry bipartite
      presequences that are cleaved twice, by MPP and the inner membrane protease
      (IMP). Here, we report that the TIM23 complex is altered in mitochondria lacking
      the IMP subunit Imp1 although none of the TIM23 components contains a bipartite
      presequence. We show that the TIM23 subunit Mgr2 is processed by IMP, but not by
      MPP. The cytosolic precursor of Mgr2 contains a carboxy-terminal sequence that
      promotes targeting to mitochondria, but impairs stable assembly and function of
      the mature TIM23 complex. IMP removes the carboxy-terminal targeting sequence and
      thus promotes proper assembly of the TIM23 complex. Our results reveal carboxy
      terminal processing as a new mechanism in the biogenesis of the mitochondrial
      inner membrane. 

PMID- 24287568
TI  - Exposure assessment for Italian population groups to deoxynivalenol deriving from
      pasta consumption.
AB  - Four hundred and seventy-two pasta samples were collected from long retail
      distribution chain sales points located in North, Central and South Italy.
      Representative criteria in the sample collection were followed in terms of number
      of samples collected, market share, and types of pasta. Samples were analysed by
      an accredited HPLC-UV method of analysis. The mean contamination level (64.8
      MUg/kg) of deoxynivalenol (DON) was  in the 95th percentile (239 MUg/kg) and 99th
      percentile (337 MUg/kg), far below the legal limit (750 MUg/kg) set by Regulation
      EC/1126/2007, accounting for about one tenth, one third and half the legal limit,
      respectively. Ninety-nine percent of samples fell below half the legal limit. On
      the basis of the obtained occurrence levels and considering the consumption rates
      reported by the Italian official database, no health concern was assessed for all
      consumer groups, being that exposure was far below the Tolerable Daily Intake
      (TDI) of 1000 ng/kg b.w/day. Nevertheless, despite this, particular attention
      should be devoted to the exposure to DON by high consumers, such as children aged
      3-5 years, who could reach the TDI even with very low levels of DON
      contamination. 

PMID- 24287569
TI  - Influence of fermentation and drying materials on the contamination of cocoa
      beans by ochratoxin A.
AB  - Ochratoxin A (OTA) is a mycotoxin produced mainly by species of Aspergillus and
      Penicillium. Contamination of food with OTA is a major consumer health hazard. In
      Cote D'Ivoire, preventing OTA contamination has been the subject of extensive
      study. The current study was conducted to evaluate the influence of fermentation
      and drying materials on the OTA content in cocoa. For each test, 7000 intact
      cocoa pods were collected, split open to remove the beans, fermented using 1 of 3
      different materials, sun-dried on 1 of 3 different platform types and stored for
      30 days. A total of 22 samples were collected at each stage of post-harvesting
      operations. The OTA content in the extracted samples was then quantified by high
      performance liquid chromatography. OTA was detected in beans at all stages of
      post-harvesting operations at varying levels: pod-opening (0.025 +/- 0.02 mg/kg),
      fermentation (0.275 +/- 0.2 mg/kg), drying (0.569 +/- 0.015 mg/kg), and storage
      (0.558 +/- 0.04 mg/kg). No significant relationships between the detected OTA
      level and the materials used in the fermentation and drying of cocoa were
      observed. 

PMID- 24287570
TI  - Impact of pH on the stability and the cross-reactivity of ochratoxin A and
      citrinin.
AB  - Mycotoxins are secondary metabolites produced by several fungi contaminating
      crops. In several countries, the maximum permitted levels of mycotoxins are found
      in foodstuffs and feedstuffs. The common strategy of mycotoxin analysis involves
      extraction, clean-up and quantification by chromatography. In this paper, we
      analyzed the reasons of underestimation of ochratoxin A (OTA) content in wine,
      and overestimation of OTA in wheat, depending on the pH of the clean-up step and
      the simultaneous presence of citrinin (CIT). We demonstrated that the increase of
      pH by adding polyethylene glycol (PEG) to wine led to an underestimation of OTA
      by conversion of OTA into open ring ochratoxin A OP-OA. In comparing three
      methods of extraction and clean-up for the determination of OTA and CIT in wheat-
      (i) an inter-laboratory validated method for OTA in cereals using immunoaffinity
      column clean-up (IAC) and extraction by acetonitrile/water; (ii) a validated
      method using IAC and extraction with 1% bicarbonate Na; and (iii) an in-house
      validated method based on acid liquid/liquid extraction--we observed an
      overestimation of OTA after immunoaffinity clean-up when CIT is also present in
      the sample, whereas an underestimation was observed when OTA was alone. Under
      neutral and alkaline conditions, CIT was partially recognized by OTA antibodies.

PMID- 24287571
TI  - Deoxynivanelol and fumonisin, alone or in combination, induce changes on
      intestinal junction complexes and in E-cadherin expression.
AB  - Fusariotoxins such as fumonisin B1 (FB1) and deoxynivalenol (DON) cause
      deleterious effects on the intestine of pigs. The aim of this study was to
      evaluate the effect of these mycotoxins, alone and in combination, on jejunal
      explants from piglets, using histological, immunohistochemical and
      ultrastructural assays. Five 24-day old pigs were used for sampling the explants.
      Forty-eight explants were sampled from each animal. Explants were incubated for 4
      hours in culture medium and medium containing FB1 (100 uM), DON (10 uM) and both
      mycotoxins (100 uM FB1 plus 10 uM DON). Exposure to all treatments induced a
      significant decrease in the normal intestinal morphology and in the number of
      goblet cells, which were more severe in explants exposed to DON and both
      mycotoxins. A significant reduction in villus height occurred in groups treated
      with DON and with co-contamination. Expression of E-cadherin was significantly
      reduced in explants exposed to FB1 (40%), DON (93%) and FB1 plus DON (100%). The
      ultrastructural assay showed increased intercellular spaces and no junction
      complexes on enterocytes exposed to mycotoxins. The present data indicate that
      FB1 and DON induce changes in cell junction complexes that could contribute to
      increase paracellular permeability. The ex vivo model was adequate for assessing
      intestinal toxicity induced by exposure of isolated or associated concentrations
      of 100 uM of FB1 and 10 uM of DON. 

PMID- 24287572
TI  - Purple ear and retiform purpura.

PMID- 24287573
TI  - Conversion of conference abstracts to publication: 3-year experience of the
      Emilia-Romagna and Marche section of the Italian Society of Internal Medicine.

PMID- 24287574
TI  - Fever and macular lesions on toes.

PMID- 24287575
TI  - Early identification of severe community-onset pneumonia in "frail elderly
      patient".

PMID- 24287577
TI  - Giant cell tumor of the distal common bile duct: report of a rare, benign entity
      that may mimic malignant biliary obstruction.

PMID- 24287576
TI  - Histone acetylation and arachidonic acid cytotoxicity in HepG2 cells
      overexpressing CYP2E1.
AB  - The aim of this work was to assess the role of ethanol-derived acetate and
      acetate-mediated histone acetylation in arachidonic acid-induced stress in HepG2
      cells and cells overexpressing CYP2E1. Cells were grown for 7 days with 1 mM
      sodium acetate or 100 mM ethanol; their acetylated histone proteins and histone
      deacetylase 2 expression was quantified using Western blot. Ethanol- or acetate
      pretreated cells were also treated for 24 h with 60 MUM arachidonic acid to
      induce oxidative stress. Cytotoxicity was estimated by lactate dehydrogenase
      release, 3-[4,5-dimethylthiazolyl-2] 2,5-diphenyltetrazolium bromide test, and by
      DNA damage, while oxidative stress was quantified using dichlorofluorescein
      diacetate. Cells grown with ethanol or acetate had increased acetylated histone
      H3 levels in both cell types and elevated acetylated histone H4 levels in cells
      overexpressing CYP2E1 but not in naive cells. In cells overexpressing CYP2E1
      grown with ethanol, expression of histone deacetylase 2 was reduced by about 40
      %. Arachidonic acid altered cell proliferation and was cytotoxic mostly to cells
      engineered to overexpress CYP2E1 but both effects were significantly lower in
      cells pretreated with ethanol or acetate. Cytotoxicity was also significantly
      decreased by 4-methylpyrazole--a CYP2E1 inhibitor and by trichostatin--an
      inhibitor of histone deacetylases. In cells pretreated with acetate or ethanol,
      the oxidative stress induced by arachidonic acid was also significantly lower.
      Our data indicate that histone hyperacetylation may in some extent protect the
      cells against oxidative stress. It is possible that acetate may act as an
      antioxidant at histone level. This mechanism may be relevant to alcohol-induced
      liver injury.

PMID- 24287578
TI  - Does prior acupuncture exposure affect perception of blinded real or sham
      acupuncture?
AB  - OBJECTIVE: To determine if acupuncture-exposed and naive participants differ in
      their perceptions of real and sham acupuncture under blinded conditions. METHODS:
      The setting was an outpatient clinic at the Colorado School of Traditional
      Chinese Medicine. Participants were between the ages of 18 and 90 years.
      Acupuncture-exposed participants had at least five prior acupuncture treatments,
      with one treatment in the month prior to the study date. Acupuncture-naive
      participants had experienced no prior acupuncture treatments. Participants with
      dementia, cognitive impairment, or neuropathy were excluded. In total, 61
      acupuncture-exposed and 59 acupuncture-naive participants were blindfolded and
      received either real acupuncture or toothpick sham acupuncture treatment.
      Following treatment, participants completed a questionnaire rating the realness
      of the acupuncture and were asked how they made this determination. We used a
      previously developed scale rating treatments from 1 (definitely real needle) to 5
      (definitely imitation needle) to assess outcome. RESULTS: Perceptions of the real
      treatment were rated as more real than sham treatments for all participants.
      Further analysis revealed that prior acupuncture exposure did not influence
      ratings of real treatments, but exposed participants rated sham treatments as
      significantly less real than naive participants. CONCLUSIONS: Acupuncture-naive
      and exposed participants both reported different perceptions of real and sham
      acupuncture using a blindfolded toothpick protocol. This suggests that future
      trials should carefully monitor participant perceptions of treatments received,
      even for naive individuals. Differences between groups further suggest that
      participants with significant and/or recent exposure to real acupuncture may
      introduce bias to blinded clinical acupuncture trials.

PMID- 24287579
TI  - The last intron of the human thrombopoietin gene enhances expression in milk of
      transgenic mice.
AB  - Introns can enhance gene expression levels. This effect is known as intron
      mediated enhancement, which is different from that of enhancers or promoters. In
      our previous study, under the control of the cytomegalovirus or goat beta-casein
      promoter, the vector containing intron V-TPOcDNA expressed the highest
      thrombopoietin (TPO) level, whereas the vector containing TPOgDNA expressed the
      lowest level. In order to verify whether intron V also improves TPO expression in
      the milk of transgenic mice, rat whey acidic protein promoter was used as
      regulatory element to construct mammary gland expression vectors including pTPOWA
      (containing TPOcDNA), pTPOWB (containing intron V-TPOcDNA), and pTPOWC
      (containing TPOgDNA). These vectors were transfected into HC-11 cells and the
      supernatants were analyzed at 48 h. The highest TPO level was found in pTPOWB
      (795 pg/mL) and the lowest level in pTPOWC (193 pg/mL). Then, corresponding
      vectors were microinjected into fertilized mice zygotes. Transgenic mice were
      identified by polymerase chain reaction and Southern blot. Enzyme-linked
      immunosorbent assay was performed to measure TPO levels in the milk of lactating
      transgenic mice. The highest and lowest TPO levels were found in transgenic mice
      carrying intron V-TPOcDNA (2,307 pg/mL) and in transgenic mice carrying TPOgDNA
      (242 pg/mL), respectively. Thus, intron V remarkably improved TPO expression in
      transgenic mice.

PMID- 24287580
TI  - Prospective associations between the family environment, family cohesion, and
      psychiatric symptoms among adolescent girls.
AB  - The present study used a longitudinal design to investigate whether parental
      values, interests, and the perceived level of expressiveness, cohesiveness and
      control in the family were associated with changes in psychiatric symptoms during
      early adolescence. We used data gathered at ages 12, 14 and 17 from 1,600
      adolescent girls in the National Heart, Lung and Blood Institute Growth and
      Health Study. Using a novel approach we found significant informant effects of
      family cohesion on psychiatric symptoms, with stronger associations for
      adolescent ratings than parental ratings. Multivariate modelling adjusting for
      family cohesion (from parents and adolescents perspective), and parents'
      depressive and eating disorder symptoms indicated parental ratings on the
      intellectual and cultural orientation of the family predicted small but
      significant increases in eating disorder symptoms, anxiety and a reduction in
      self-worth 2-years later. Parental control also predicted a reduction in anxiety
      and family expressiveness was related to increases in self-worth. 

PMID- 24287581
TI  - The longitudinal link between parenting and child aggression: the moderating
      effect of attachment security.
AB  - This study examined whether infant attachment security moderates the association
      between parenting in preschool and later aggressive behavior among a sample of
      children at high risk for developing conduct problems. Participants were 82
      adolescent mother-child dyads recruited from the community. Infant attachment
      status at age 1 year was measured using the Strange Situation. When children were
      aged 4.5 years, mothers reported on their self-efficacy in regards to parenting,
      and mothers' positive parenting and criticism were coded from direct observations
      of parent-child interactions. In grade 1, mothers reported on their children's
      aggressive behavior. Infant secure attachment significantly moderated the
      association between observed maternal criticism and child aggression. That is,
      among insecurely attached children, higher levels of maternal criticism were
      associated with more severe aggression. This longitudinal finding suggests that a
      secure attachment may buffer the deleterious effects of harsh parenting on child
      aggression. 

PMID- 24287583
TI  - Interactions of gold-based drugs with proteins: crystal structure of the adduct
      formed between ribonuclease A and a cytotoxic gold(III) compound.
AB  - The reaction of Auoxo6, a dinuclear gold(III) complex, with the model protein
      bovine pancreatic ribonuclease is explored here by X-ray diffraction and ESI mass
      spectrometry. Data provide clues on the processes of adduct formation and of
      enzyme inhibition and, inductively, on the likely mode of action of this
      metallodrug.

PMID- 24287582
TI  - Baseline factors and very early viral response (week 1) for predicting sustained
      virological response in telaprevir-based triple combination therapy for Japanese
      genotype 1b chronic hepatitis C patients: a multicenter study.
AB  - BACKGROUND: Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a
      rapid virological response (RVR) have been reported as predictors for a sustained
      virological response (SVR) to telaprevir (TVR)-based triple combination therapy.
      However, the association between SVR and viral kinetics earlier than week 4 after
      initiation of therapy remains unclear. Thus, we evaluated the SVR prediction
      ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at
      week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic
      hepatitis C (CHC) patients. METHODS: A total of 156 Japanese CHC patients
      received a 24-week regimen of TVR-based therapy. Baseline factors and reduction
      in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed
      for SVR prediction. RESULTS: Multiple logistic regression analysis for SVR in TVR
      based therapy identified the IL28B TT genotype, a reduction of >= 4.7 log10 IU/mL
      in HCV RNA levels at week 1, RVR, and treatment-naive/relapse. Whereas the SVR
      rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1
      in patients with the TT genotype, a reduction of >= 4.7 log10 IU/mL in HCV RNA
      levels at week 1 was the strongest predictor of SVR in patients with the non-TT
      genotype, as determined by multiple logistic regression analysis (P = 0.0043).
      CONCLUSIONS: The IL28B TT genotype is the most important baseline factor for
      predicting SVR, and a >= 4.7 log10 IU/mL reduction in HCV RNA at week 1 is a
      useful very early on-treatment predictor of SVR, especially in the non-TT
      genotype.

PMID- 24287584
TI  - Merkel cell carcinoma of the eyelid: management and prognosis.
AB  - IMPORTANCE: The literature on Merkel cell carcinoma (MCC) of the eyelid remains
      scarce, and there has yet to be a study using the most up-to-date TNM staging
      system for this rare but aggressive tumor. OBJECTIVE: To analyze the TNM stage,
      management, and outcomes of patients with MCC of the eyelid. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective case series of 21 patients from 5 tertiary referral
      centers in the United Kingdom and Australia with primary MCC of the eyelid
      presenting at a median age of 77 years, with median follow-up of 54 months.
      Tumors were staged according to the American Joint Committee on Cancer, 7th
      edition, TNM criteria for eyelid carcinoma and MCC. MAIN OUTCOMES AND MEASURES:
      TNM stage, treatment modalities, and clinical outcome. RESULTS: The eyelid
      carcinoma TNM stages were T2aN0M0 for 5 patients, T2bN0M0 for 7 patients, T3aN0M0
      for 4 patients, T3bN0M0 for 3 patients, T2bN1M0 for 1 patient, and T3aN1M0 for 1
      patient. The MCC TNM stages were T1N0M0 for 12 patients, T2N0M0 for 7 patients,
      T1N1M0 for 1 patient, and T2N1M0 for 1 patient. One patient had a sentinel lymph
      node biopsy, and 8 patients underwent head/neck imaging. Eighteen patients
      underwent a wide local excision, 12 with a paraffin section and 6 with a frozen
      section. Two patients underwent Mohs surgery, 1 of whom required an orbital
      exenteration. Twelve patients (57%) received adjuvant radiotherapy, and 2
      patients received chemotherapy. The local recurrence rate was 10%, the regional
      nodal recurrence rate was 10%, and the distant metastatic recurrence rate was
      19%. The lowest T category tumor metastasizing to both regional nodes and distant
      locations was a T2a (eyelid TNM)/T1 (Merkel TNM) tumor measuring 8 mm. Two
      patients with T3a (eyelid TNM)/T2 (Merkel TNM) tumors died of metastatic MCC.
      CONCLUSIONS AND RELEVANCE: The majority of patients with MCC of the eyelid
      present with localized eyelid disease of T category T2 (eyelid TNM)/T1 (Merkel
      TNM). A wide local excision with margin control remains the mainstay of
      treatment, whereas the use of radiotherapy is institution specific. Tumors with a
      low T category are associated with regional nodal and distant metastatic disease.
      It may therefore be reasonable to consider a sentinel lymph node biopsy or strict
      regional lymph node surveillance for all MCCs of the eyelid, regardless of T
      category or size.

PMID- 24287586
TI  - Oxidative C(sp3)-H bond cleavage, C-C and C=C coupling at a boron center with O2
      as the oxidant mediated by platinum(II).
AB  - Dimethyl- and diphenylplatinum(II) fragments Pt(II)R2 (R = Me, Ph) enable facile
      and efficient oxidative C(sp(3))-H bond cleavage and stepwise C-C and C=C
      coupling at the boron atom of a coordinated 1,5-cyclooctanediyldi(2
      pyridyl)borato ligand with O2 as the sole oxidant.

PMID- 24287585
TI  - Development of novel DNA vaccine for VEGF in murine cancer model.
AB  - We developed DNA vaccine for vascular endothelial growth factor (VEGF), which may
      provide the therapeutic option instead of anti-VEGF antibody, bevacizumab.
      Plasmid containing VEGF mini-gene was constructed in the insertion of B-cell
      epitope of Hepatitis B core protein [HBc-VEGF], which was an epitope carrier.
      High titer of anti-VEGF antibody was observed in BALB/c mice which were
      intramuscularly immunized with HBc-VEGF by electropolator. In mice inoculated
      with colon 26 cells, tumor volume and microvessel density was decreased in HBc
      VEGF with a significant prolonged survival. Co-treatment of purified IgG from
      immunized mice with HBc-VEGF showed in vitro neutralizing activity for VEGF
      induced ERK phosphorylation and tube formation in cultured endothelial cells.
      Furthermore, intravitreally injection of this purified IgG reduced the neovessel
      formation in the mouse oxygen-induced retinopathy and laser-induced choroidal
      neovascularization models. These results first provided that DNA vaccine against
      VEGF possessed the anti-angiogenic effect, leading to prolonged survival in mouse
      cancer model. 

PMID- 24287587
TI  - Rapid synthesis of nitrogen-doped graphene for a lithium ion battery anode with
      excellent rate performance and super-long cyclic stability.
AB  - Chemical doping of nitrogen into graphene can significantly enhance the
      reversible capacity and cyclic stability of the graphene-based lithium ion
      battery (LIB) anodes, and first principles calculations based on density
      functional theory suggested that pyridinic-N shows stronger binding with Li with
      reduced energy barrier for Li diffusion and thus is more effective for Li storage
      than pyrrolic and graphitic-N. Here, we report a novel and rapid (~30 seconds)
      process to fabricate nitrogen-doped graphene (NGr) by simultaneous thermal
      reduction of graphene oxide with ammonium hydroxide. The porous NGr with dominant
      pyridinic N atoms displays greatly enhanced reversible capacities, rate
      performance and exceptional cyclic stability as compared with pristine graphene.
      The reversible discharge capacity of the NGr electrode cycled between 0.01-3 V
      can reach 453 mA h g(-1) after 550 cycles at a charge rate of 2 A g(-1) (~5.4 C),
      and 180 mA h g(-1) after 2000 cycles at a high charge rate of 10 A g(-1) (~27 C)
      without any capacity fading. When charged within 0.01-1.5 V, the NGr anode still
      exhibits high reversible capacities of 224 mA h g(-1) and 169 mA h g(-1) after
      700 cycles and 800 cycles at a charge rate of 1 A g(-1) and 5 A g(-1),
      respectively. Ex situ X-ray photoelectron spectroscopy (XPS) analysis of the NGr
      electrode upon lithiation and delithiation indicated that the pyridinic-N
      dominates the capacity enhancement at 3 V, while the pyrrolic-N contributes
      primarily to Li ion storage below 1.5 V.

PMID- 24287588
TI  - Photoresponsive vesicle permeability based on intramolecular host-guest
      inclusion.
AB  - This article describes light-responsive vesicles that can release their contents
      in response to a light-sensitive molecular trigger. To this end, liposomes were
      equipped with amphiphilic beta-cyclodextrin that was covalently labeled with
      azobenzene. Using dye encapsulation and confocal laser scanning microscopy, we
      show that the permeability of these vesicles strongly increases upon UV
      irradiation (lambda = 350 nm) with concomitant isomerization of apolar trans
      azobenzene to polar cis-azobenzene on the liposome surface. 

PMID- 24287589
TI  - Ion mobility spectrometry for pharmacokinetic studies--exemplary application.
AB  - Breath analysis is an attractive non-invasive method for diagnosis and
      therapeutic monitoring. It uses endogenously produced compounds and metabolites
      of isotopically labeled precursors. In order to make such tests clinically
      useful, it is important to have relatively small portable instruments detecting
      volatile compounds within short time. A particularly promising analytical
      technique is ion mobility spectrometry (IMS) coupled to a multi capillary column
      (MCC). This paper focuses on demonstrating the suitability of breath analysis for
      pharmacokinetic applications using MCC-IMS with respect to practicability and
      reproducibility testing the model substrate eucalyptol. Validation of the MCC-IMS
      measurements were performed using proton transfer reaction mass spectrometry (PTR
      MS) and resulted in an excellent correspondence of the time-dependent
      concentrations presented by the two different analytical techniques. Moreover,
      the good accordance in variance of kinetic parameters with repeated measures, and
      the determined inter-subject differences indicate the eligibility of the analysis
      method. 

PMID- 24287590
TI  - Mesoporous carbon-coated LiFePO4 nanocrystals co-modified with graphene and Mg2+
      doping as superior cathode materials for lithium ion batteries.
AB  - In this work, mesoporous carbon-coated LiFePO4 nanocrystals further co-modified
      with graphene and Mg(2+) doping (G/LFMP) were synthesized by a modified
      rheological phase method to improve the speed of lithium storage as well as
      cycling stability. The mesoporous structure of LiFePO4 nanocrystals was designed
      and realized by introducing the bead milling technique, which assisted in forming
      sucrose-pyrolytic carbon nanoparticles as the template for generating mesopores.
      For comparison purposes, samples modified only with graphene (G/LFP) or Mg(2+)
      doping (LFMP) as well as pure LiFePO4 (LFP) were also prepared and investigated.
      Microscopic observation and nitrogen sorption analysis have revealed the
      mesoporous morphologies of the as-prepared composites. X-ray diffraction (XRD)
      and Rietveld refinement data demonstrated that the Mg-doped LiFePO4 is a single
      olivine-type phase and well crystallized with shortened Fe-O and P-O bonds and a
      lengthened Li-O bond, resulting in an enhanced Li(+) diffusion velocity.
      Electrochemical properties have also been investigated after assembling coin
      cells with the as-prepared composites as the cathode active materials.
      Remarkably, the G/LFMP composite has exhibited the best electrochemical
      properties, including fast lithium storage performance and excellent cycle
      stability. That is because the modification of graphene provided active sites for
      nuclei, restricted the in situ crystallite growth, increased the electronic
      conductivity and reduced the interface reaction current density, while, Mg(2+)
      doping improved the intrinsically electronic and ionic transfer properties of LFP
      crystals. Moreover, in the G/LFMP composite, the graphene component plays the
      role of "cushion" as it could quickly realize capacity response, buffering the
      impact to LFMP under the conditions of high-rate charging or discharging, which
      results in a pre-eminent rate capability and cycling stability. 

PMID- 24287592
TI  - Utilising non-consensus pathology measurements to improve the diagnosis of
      oesophageal cancer using a Raman spectroscopic probe.
AB  - The application of semi-supervised methodology to improve the classification
      performance of a Raman spectroscopic probe for the diagnosis of oesophageal
      cancer is described. It is well known that gold standard histopathology diagnosis
      can be highly subjective, particularly for diseases which have several stages,
      such as cancer. A 'consensus' pathology decision can be obtained to ensure a
      robust gold standard by obtaining a diagnosis from several experts and samples
      are then only included in standard classification models if they have been
      assigned the same pathology by all experts. This can result in a significant
      number of samples that are excluded from the analysis as no consensus was
      reached. In this work semi-supervised methodology was used to extend Principal
      Component Analysis followed by Linear Discriminant Analysis (PCA-LDA) to
      incorporate samples without consensus pathology when discriminating between
      benign and oesophageal cancer specimens measured using a Raman endoscopic probe
      ex vivo. We demonstrate that a fully semi-supervised approach improved
      sensitivity and specificity from 73% and 78% (PCA-LDA) to 78% and 84% (semi
      supervised) for discriminating between intestinal metaplasia and dysplasia and
      from 44% and 66% (PCA-LDA) to 63% and 72% (semi-supervised) when discriminating
      between intestinal metaplasia and low grade dysplasia. 

PMID- 24287593
TI  - Fumonisin measurement from maize samples by high-performance liquid
      chromatography coupled with corona charged aerosol detector.
AB  - Fumonisins are a class of mycotoxins produced mainly by Fusarium species, which
      is primary fungal contaminant of the maize and maize-derived products around the
      world. The B-series fumonisins (FB1, FB2 and FB3) are the most abundant and toxic
      constituent; thus, their levels are regulated generally worldwide. In this study,
      we developed a reliable method for the measurement of fumonisin FB1, FB2 and FB3
      mycotoxins from maize samples without the time-consuming derivatization step
      using a high-performance liquid chromatograph coupled with corona charged aerosol
      detector. The detection and quantitation limit of the whole method were 0.02 and
      0.04 mg/kg for each fumonisins, respectively. The detection linearity was tested
      in the calibration range of 2 orders of magnitude and the recoveries from the
      spiked samples were determined. The developed method proved to be sufficient to
      measure the maximum residue levels of fumonisins, which are specified in European
      Union and United States in maize and maize-based products. 

PMID- 24287594
TI  - Does long-term partial sodium channel blockade alter disease progression in MS?
      Evidence from a retrospective study.
AB  - BACKGROUND: There is accumulating evidence that long-term disability and disease
      progression in multiple sclerosis (MS) are due to prolonged sodium channel
      opening along demyelinated axons. Despite good evidence in animal models of MS
      that partial voltage-gated sodium channel (VGSC) blockade reduces disease
      progression, little is known about its effects in patients, despite widespread
      use of such agents in the symptomatic management of MS. OBJECTIVE: To determine
      if long-term exposure to the VGSC-blocking drug carbamazepine (CBZ) alters
      disease progression in MS. METHODS: Using a retrospective chart review of
      patients diagnosed with MS, we compared progression of disability between
      patients exposed the VGSC blocker CBZ with those who were not exposed to the
      drug. Both whole-group and matched case-control analyses were performed after
      correcting for the influence of age, gender, MS subtype, expanded disability
      status score at diagnosis, use of disease-modifying therapy, and year of initial
      therapy. The multiple sclerosis severity scale (MSSS) was used as a measure of
      disease severity. The primary outcome measure was MSSS score difference between
      groups. RESULTS: Four hundred patients were included; 51 received CBZ symptomatic
      therapy (average duration of therapy 27 months). There was no significant
      difference in mean MSSS between the two groups in either the whole group
      comparison (p = 0.63) or the matched analysis (p = 0.12). CONCLUSION: Despite
      preclinical evidence suggesting a neuroprotective role of VGSC blockers in animal
      models of MS, this retrospective study suggests that long-term exposure to the
      VGSC-blocking drug CBZ fails to alter long-term disability and disease
      progression in MS patients.

PMID- 24287595
TI  - Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin
      dynamics.
AB  - The ubiquitously expressed adapter proteins Nck1/2 interact with a multitude of
      effector molecules to regulate diverse cellular functions including cytoskeletal
      dynamics. Here we show that Nck1, but not Nck2, is a substrate of c-Cbl-mediated
      ubiquitination. We uncover lysine 178 in Nck1 as the evolutionarily conserved
      ubiquitin acceptor site. We previously reported that synaptopodin, a proline-rich
      actin-binding protein, induces stress fibres by blocking the Smurf1-mediated
      ubiquitination of RhoA. We now find that synaptopodin competes with c-Cbl for
      binding to Nck1, which prevents the ubiquitination of Nck1 by c-Cbl. Gene
      silencing of c-Cbl restores Nck1 protein abundance and stress fibres in
      synaptopodin knockdown cells. Similarly, expression of c-Cbl-resistant
      Nck1(K178R) or Nck2 containing the SH3 domain 2 of Nck1 restores stress fibres in
      synaptopodin-depleted podocytes through activation of RhoA signalling. These
      findings reveal proteasomal regulation as a key factor in the distinct and non
      redundant effects of Nck on RhoA-mediated actin dynamics. 

PMID- 24287596
TI  - First isolation of a giant virus from wild Hirudo medicinalis leech: Mimiviridae
      isolation in Hirudo medicinalis.
AB  - Giant viruses and amoebae are common in freshwater, where they can coexist with
      other living multicellular organisms. We screened leeches from the species Hirudo
      medicinalis for giant viruses. We analyzed five H. medicinalis obtained from
      Tunisia (3) and France (2). The leeches were decontaminated and then dissected to
      remove internal parts for co-culture with Acanthamoeba polyphaga. The genomes of
      isolated viruses were sequenced on a 454 Roche instrument, and a comparative
      genomics analysis was performed. One Mimivirus was isolated and the strain was
      named Hirudovirus. The genome assembly generated two scaffolds, which were
      1,155,382 and 25,660 base pairs in length. Functional annotations were identified
      for 47% of the genes, which corresponds to 466 proteins. The presence of
      Mimividae in the same ecological niche as wild Hirudo may explain the presence of
      the mimivirus in the digestive tract of the leech, and several studies have
      already shown that viruses can persist in the digestive tracts of leeches fed
      contaminated blood. As leeches can be used medically and Mimiviruses have the
      potential to be an infectious agent in humans, patients treated with leeches
      should be surveyed to investigate a possible connection. 

PMID- 24287597
TI  - Effects and effectiveness of two RNAi constructs for resistance to Pepper golden
      mosaic virus in Nicotiana benthamiana plants.
AB  - ToChLPV and PepGMV are Begomoviruses that have adapted to a wide host range and
      are able to cause major diseases in agronomic crops. We analyzed the efficacy of
      induced resistance to PepGMV in Nicotiana benthamiana plants with two constructs:
      one construct with homologous sequences derived from PepGMV, and the other
      construct with heterologous sequences derived from ToChLPV. Plants protected with
      the heterologous construct showed an efficacy to decrease the severity of
      symptoms of 45%, while plants protected with the homologous construct showed an
      efficacy of 80%. Plants protected with the heterologous construct showed a
      reduction of incidence of 42.86%, while the reduction of incidence in plants
      protected with the homologous construct was 57.15%. The efficacy to decrease
      viral load was 95.6% in plants protected with the heterologous construct, and
      99.56% in plants protected with the homologous construct. We found, in both
      constructs, up-regulated key components of the RNAi pathway. This demonstrates
      that the efficacy of the constructs was due to the activation of the gene
      silencing mechanism, and is reflected in the decrease of viral genome copies, as
      well as in recovery phenotype. We present evidence that both constructs are
      functional and can efficiently induce transient resistance against PepGMV
      infections. This observation guarantees a further exploration as a strategy to
      control complex Begomovirus diseases in the field. 

PMID- 24287599
TI  - Experience on evaluation of passive neutron dosemeters according to ISO 21909.
AB  - This paper presents experience, found problems and lessons learnt during the
      evaluations of various TLD and CR-39 passive neutron dosemeters according to ISO
      21909. Recommendations for the standard, being currently in revision, are also
      discussed. 

PMID- 24287598
TI  - Genetic modification of hematopoietic stem cells as a therapy for HIV/AIDS.
AB  - The combination of genetic modification and hematopoietic stem cell (HSC)
      transplantation may provide the necessary means to develop an alternative
      treatment option to conventional antiretroviral therapy. As HSCs give rise to all
      hematopoietic cell types susceptible to HIV infection, modification of HSCs is an
      ideal strategy for the development of infection-resistant immune cell
      populations. Although promising results have been obtained in multiple animal
      models, additional evidence is needed to convincingly demonstrate the feasibility
      of this approach as a treatment of HIV-1 infected patients. Here, we review the
      potential of HSC transplantation and the recently identified limitations of this
      approach. Using the Berlin Patient as a model for a functional cure, we contrast
      the confines of autologous versus allogeneic transplantation. Finally, we suggest
      that although autologous, gene-modified HSC-transplantation may significantly
      reduce plasma viremia, reaching the lower detection limits currently obtainable
      through daily HAART will remain a challenging endeavor that will require
      innovative combinatorial therapies. 

PMID- 24287600
TI  - Measurements of radon concentrations in waters and soil gas of Zonguldak, Turkey.
AB  - The radon concentrations in soil-gas and water samples (in the form of springs,
      catchment, tap, thermal) used as drinking water or thermal were measured using a
      professional radon monitor AlphaGUARD PQ 2000PRO. The measured radon
      concentrations in water samples ranged from 0.32 to 88.22 Bq l(-1). Most of radon
      levels in potable water samples are below the maximum contaminant level of 11 Bq
      l(-1) recommended by the US Environmental Protection Agency. The calculated
      annual effective doses due to radon intake through water consumption varied from
      0.07 to 18.53 uSv y(-1). The radon concentrations in soil gas varied from 295.67
      to 70 852.92 Bq m(-3). The radon level in soil gas was found to be higher in the
      area close to the formation boundary thrust and faults. No correlation was
      observed between radon concentrations in groundwater and soil gas. Also, no
      significant correlation was observed between soil-gas radon and temperature,
      pressure and humidity. The emanation of radon from groundwater and soil gas is
      controlled by the geological formation and by the tectonic structure of the area.

PMID- 24287601
TI  - Mechanistic pharmacokinetic/target engagement/pharmacodynamic (PK/TE/PD) modeling
      in deciphering interplay between a monoclonal antibody and its soluble target in
      cynomolgus monkeys.
AB  - For therapeutic monoclonal antibodies (mAbs) against soluble ligands, the free
      ligand level can, theoretically, be used as a surrogate for efficacy. However, it
      can be extremely challenging technically to measure free ligand level in the
      presence of an excessive amount of antibody-ligand complex. The interplay among
      such mAbs, ligands, and the downstream pharmacodynamic (PD) effects has not been
      well defined. Using siltuximab and interleukin-6 (IL-6) as model compounds, a
      pharmacokinetic (PK)/target engagement (TE) model was established via
      simultaneous fitting of total siltuximab, total IL-6, and free IL-6 concentration
      profiles following a low dose of siltuximab in cynomolgus monkeys. The model
      adequately captured the observed data and provided estimation of model parameters
      with good precision. The PK/TE model was used to predict free IL-6 profiles at
      higher siltuximab doses, where the accurate determination of free IL-6
      concentration became technically too difficult. The measured free IL-6 levels
      from the low-dose groups and PK/TE model-predicted free IL-6 levels from the high
      dose groups were used to drive an indirect response TE/PD model to describe the
      concentration-effect relationship between free IL-6 and C-reactive protein (CRP).
      The TE/PD model adequately captured both CRP elevation and CRP suppression in
      response to free IL-6 concentration change from baseline with a linear
      stimulation function, providing direct evidence that the PK/TE model-predicted
      free IL-6 levels from the high-dose groups were accurate. Overall, the results
      provided an integrated PK/TE/PD modeling and bioanalytical framework for
      prediction of efficacious dose levels and duration of action for mAbs against
      soluble ligands with rapid turnover. 

PMID- 24287602
TI  - Effects of upper respiratory tract illnesses, ibuprofen and caffeine on reaction
      time and alertness.
AB  - RATIONALE: Compared with healthy individuals, those with upper respiratory tract
      illnesses (URTIs) report reduced alertness and have slower reaction times. It is
      important to evaluate medication that can remove this behavioural malaise.
      OBJECTIVES: The aim of this study was to compare the effects of a combination of
      ibuprofen plus caffeine with ibuprofen and caffeine alone, and placebo on malaise
      associated with URTIs, as measured by psychomotor performance and mood testing.
      METHODS: Volunteers were randomly assigned to one of four medication conditions
      as follows: 200 mg ibuprofen and 100 mg caffeine; 200 mg ibuprofen; 100 mg
      caffeine; placebo. A single oral dose was given and testing followed for 3 h.
      Efficacy variables were based on the volunteers' performance, measured by
      psychomotor performance and mood. RESULTS: The pre-drug results confirmed that
      those with an URTI had a more negative mood and impaired performance. Results
      from the simple reaction time task, at both 55- and 110-min post-dosing, showed
      that a single-dose of caffeinated products (I200/C100 and CAF100) led to
      significantly faster reaction times than IBU200 and placebo. These effects were
      generally confirmed with the other performance tasks. Subjective measures showed
      that the combination of ibuprofen and caffeine was superior to the other
      conditions. There were no serious adverse events reported, and study medication
      was well tolerated. CONCLUSIONS: The results from the post-drug assessments
      suggest that a combination of ibuprofen and caffeine was the optimum treatment
      for malaise associated with URTIs in that it had significant effects on objective
      performance and subjective measures.

PMID- 24287603
TI  - Behavioral effects of dopamine receptor inactivation during the adolescent
      period: age-dependent changes in dorsal striatal D2(High) receptors.
AB  - RATIONALE: Dopamine (DA) receptor inactivation produces opposing behavioral
      effects across ontogeny. For example, inactivating DA receptors in the dorsal
      striatum attenuates DA agonist-induced behaviors of adult rats, while
      potentiating the locomotor activity of preweanling rats. OBJECTIVE: The purpose
      of this study was to determine if DA receptor inactivation potentiates the DA
      agonist-induced locomotor activity of adolescent rats and whether alterations in
      D2(High) receptors are responsible for this effect. METHODS: In the behavioral
      experiment, the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ) or its vehicle (100 % dimethyl sulfoxide, DMSO) was
      bilaterally infused into the dorsal striatum on postnatal day (PD) 39. On PD 40,
      adolescent rats were given intrastriatal infusions of the DA agonist R(-)
      propylnorapomorphine (NPA) or vehicle and locomotor activity was measured for 40
      min. In the receptor binding experiment, rats received IP injections of EEDQ or
      DMSO (1:1 (v/v) in distilled water) on PD 17, PD 39, or PD 84. One day later,
      striatal samples were taken and subsequently assayed for D2-specific binding and
      D2(High) receptors using [(3)H]-domperidone. RESULTS: Unlike what is observed
      during the preweanling period, EEDQ attenuated the NPA-induced locomotor activity
      of adolescent rats. EEDQ reduced D2 receptor levels in the dorsal striatum of all
      age groups while increasing the proportion of D2(High) receptors. Regardless of
      pretreatment condition (i.e., DMSO or EEDQ), preweanling rats had a greater
      percentage of D2(High) receptors than adolescent or adult rats. CONCLUSIONS: DA
      receptor inactivation affects the behaviors of preweanling and older rats
      differently. The DA supersensitivity exhibited by EEDQ-treated preweanling rats
      may result from an excess of D2(High) receptors.

PMID- 24287604
TI  - Role of oxytocin receptors in modulation of fear by social memory.
AB  - RATIONALE: Oxytocin receptors (Oxtr) are important mediators of social learning
      and emotion, with bidirectional effects on fear and anxiety. Contrary to the
      anxiolytic actions of Oxtr in the amygdala, we recently showed that Oxtr in the
      lateral septum mediate the enhancement of fear conditioning by social defeat in
      mice. OBJECTIVES: Using positive social interactions, which impair fear
      conditioning, here we attempted to delineate whether the role of septal Oxtr in
      fear regulation depends on the valence of the social memory. METHODS:
      Pharmacological and genetic manipulations of lateral septal Oxtr were combined
      with the social buffering of fear paradigm, in which pre-exposure to nonfearful
      conspecifics reduces subsequent contextual fear conditioning, as revealed by
      decreased freezing behavior. RESULTS: Antagonism and down-regulation of Oxtr in
      the lateral septum abolished, while oxytocin (Oxt) administration before pre
      exposure to nonfearful conspecifics facilitated the decrease of freezing
      behavior. CONCLUSIONS: The septal oxytocin system enhances memory of social
      interactions regardless of their valence, reducing fear after positive and
      enhancing fear after negative social encounters. These findings explain, at least
      in part, the seemingly bidirectional role of Oxt in fear regulation.

PMID- 24287605
TI  - Improving care of post-infarct patients: effects of disease management programmes
      and care according to international guidelines.
AB  - BACKGROUND: Cardiac disease management programmes (CHD-DMPs) and secondary
      cardiovascular prevention guidelines aim to improve complex care of post
      myocardial infarction (MI) patients. In Germany, CHD-DMPs, in addition to
      incorporating medical care according to guidelines (guideline-care), also ensure
      regular quarterly follow-up. Thus, our aim was to examine whether CHD-DMPs
      increase the frequency of guideline-care and whether CHD-DMPs and guideline-care
      improve survival over 4 years. METHODS: The study included 975 post-MI patients,
      registered by the KORA-MI Registry (Augsburg, Germany), who completed a
      questionnaire in 2006. CHD-DMP enrolment was reported by physicians. Guideline
      care was based on patient reports regarding medical advice (smoking, diet, or
      exercise) and prescribed medications (statins and platelet aggregation inhibitors
      plus beta-blockers or renin-angiotensin inhibitors). All-cause mortality until
      December 31, 2010 was based on municipal registration data. Cox regression
      analyses were adjusted for age, sex, education, years since last MI, and smoking
      and diabetes. RESULTS: Physicians reported that 495 patients were CHD-DMP
      participants. CHD-DMP participation increased the likelihood of receiving
      guideline-care (odds ratio 1.55, 95% CI 1.20; 2.02) but did not significantly
      improve survival (hazard rate 0.90, 95% CI 0.64-1.27). Guideline-care
      significantly improved survival (HR 0.41, 95% CI 0.28; 0.59). Individual
      guideline-care components, which significantly improved survival, were beta
      blockers, statins and platelet aggregation inhibitors. However, these improved
      survival less than guideline-care. CONCLUSIONS: This study shows that CHD-DMPs
      increase the likelihood of guideline care and that guideline care is the
      important component of CHD-DMPs for increasing survival. A relatively high
      percentage of usual care patients receiving guideline-care indicate high quality
      of care of post-MI patients. Reasons for not implementing guideline-care should
      be investigated.

PMID- 24287607
TI  - Arbuscular mycorrhizal symbiosis alleviates detrimental effects of saline
      reclaimed water in lettuce plants.
AB  - The present study evaluated the effects of inoculation with arbuscular
      mycorrhizal fungi (AMF; Glomus iranicum var. tenuihypharum sp. nova) on the
      physiological performance and production of lettuce plants grown under greenhouse
      conditions and supplied with reclaimed water (RW; urban-treated wastewater with
      high electrical conductivity; 4.19 dS m(-1)). Four treatments, fresh water, fresh
      water plus AMF inoculation, RW and RW plus AMF inoculation, were applied and
      their effects, over time, analyzed. Root mycorrhizal colonization, plant biomass,
      leaf-ion content, stomatal conductance and net photosynthesis were assessed.
      Overall, our results highlight the significance of the AMF in alleviation of salt
      stress and their beneficial effects on plant growth and productivity. Inoculated
      plants increased the ability to acquire N, Ca, and K from both non-saline and
      saline media. Moreover, mycorrhization significantly reduced Na plant uptake.
      Under RW conditions, inoculated plants also showed a better performance of
      physiological parameters such as net photosynthesis, stomatal conductance and
      water-use efficiency than non-mycorrhizal plants. Additionally, the high
      concentration of nutrients already dissolved in reclaimed water suggested that
      adjustments in the calculation of the fertigation should be conducted by farmers.
      Finally, this experiment has proved that mycorrhization could be a suitable way
      to induce salt stress resistance in iceberg lettuce crops as plants supplied with
      reclaimed water satisfied minimum legal commercial size thresholds. Moreover, the
      maximum values of Escherichia coli in the reclaimed water were close to but never
      exceeded the international thresholds established (Spanish Royal Decree
      1620/2007; Italian Decree, 2003) and hence lettuces were apt for sale.

PMID- 24287606
TI  - Radiofrequency ablation for the treatment of recurrent bone and soft-tissue
      sarcomas in non-surgical candidates.
AB  - AIMS: The aim of this study was to evaluate the safety and clinical utility of
      radiofrequency ablation (RFA) retrospectively in non-surgical candidates with
      recurrent bone and soft-tissue sarcomas. METHODS: Percutaneous RFA was used in 52
      patients (21 female, 31 male; mean age, 52.2 +/- 21.1 years; range 10-87 years)
      with recurrent bone and soft-tissue sarcomas. The number of tumors was 3 or fewer
      in 23 patients (44.2 %) and 4 or more in the others, with a mean maximum tumor
      diameter of 3.0 +/- 3.7 cm (range 0.5-18 cm). Safety, tumor control, and
      prognosis were evaluated. RESULTS: All tumors were ablated after RFA in 21
      patients (40.4 %, 21/52), although 14 experienced re-recurrence. Tumors were
      controlled in 8 cases of recurrence by repeat RFA (n = 7) and surgical
      intervention (n = 1). Therefore, 15 patients (28.8 %, 15/52) were tumor-free at
      the end of follow-up (mean follow-up 25.5 +/- 24.2 months; range 3.9-117 months).
      Residual tumors were found after RFA in the other 31 patients (59.6 %, 31/52).
      Overall survival rates were 73.4 % (95 % CI 61.0-85.9 %) at 1 year, 39.3 % (95 %
      CI 23.6-54.9 %) at 3 years, and 34.3 % (95 % CI 18.0-50.7 %) at 5 years in all
      patients. Recurrence-free interval (p = 0.040), tumor number (p = 0.0094), and
      complete tumor ablation (p < 0.0001) were detected as significant prognostic
      factors in univariate analysis. The latter two factors were significant in
      multivariate analysis. The rate of major complications was 0.9 %. CONCLUSIONS:
      RFA is a safe and useful therapeutic option for treatment of recurrent bone and
      soft-tissue sarcomas. Prognostic factors found in this study will help to
      identify those patients who would benefit from RFA.

PMID- 24287608
TI  - Functional systems with orthogonal dynamic covalent bonds.
AB  - This review summarizes the use of orthogonal dynamic covalent bonds to build
      functional systems. Dynamic covalent bonds are unique because of their dual
      nature. They can be as labile as non-covalent interactions or as permanent as
      covalent bonds, depending on conditions. Examples from nature, reaching from the
      role of disulfides in protein folding to thioester exchange in polyketide
      biosynthesis, indicate how dynamic covalent bonds are best used in functional
      systems. Several synthetic functional systems that employ a single type of
      dynamic covalent bonds have been reported. Considering that most functional
      systems make simultaneous use of several types of non-covalent interactions
      together, one would expect the literature to contain many examples in which
      different types of dynamic covalent bonds are similarly used in tandem. However,
      the incorporation of orthogonal dynamic covalent bonds into functional systems is
      a surprisingly rare and recent development. This review summarizes the available
      material comprehensively, covering a remarkably diverse collection of functions.
      However, probably more revealing than the specific functions addressed is that
      the questions asked are consistently quite unusual, very demanding and highly
      original, focusing on molecular systems that can self-sort, self-heal, adapt,
      exchange, replicate, transcribe, or even walk and "think" (logic gates). This
      focus on adventurous chemistry off the beaten track supports the promise that
      with orthogonal dynamic covalent bonds we can ask questions that otherwise cannot
      be asked. The broad range of functions and concepts covered should appeal to the
      supramolecular organic chemist but also to the broader community. 

PMID- 24287609
TI  - Effects of copaene, a tricyclic sesquiterpene, on human lymphocytes cells in
      vitro.
AB  - In this study, the cytotoxic, genotoxic/antigenotoxic and antioxidant/oxidant
      activity of copaene (COP), a plant-derived tricyclic sesquiterpene, on human
      lymphocyte cultures (n = 5) was investigated. COP was added into culture tubes at
      various concentrations (0, 10, 25, 50, 100, 200 and 400 mg/L). While the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate
      dehydrogenase (LDH) assays were used for viability and cytotoxic evaluations, the
      micronucleus (MN) and sister chromatid exchange (SCE) assays were used for
      genetic evaluations. Moreover, total antioxidant capacity (TAC) and total
      oxidative status analysis were used for biochemical evaluations. According to LDH
      and MTT assays COP significantly reduced cell proliferation at high
      concentrations (200 and 400 mg/L). In addition, there was no significant increase
      (P < 0.05) in both SCE and MN frequencies of cultures treated with COP as
      compared to controls. We have also concluded that concentrations of COP of 50 and
      100 mg/L increased TAC level when compared to the controls. In conclusion, in
      this study it has been reported for the first time that copaene is not genotoxic
      and it increases the antioxidant capacity in human lymphocyte cultures. 

PMID- 24287610
TI  - The role of adipose-derived stromal cells and hydroxypropylmethylcellulose in
      engineering cartilage tissue in vivo.
AB  - This study demonstrated a newly developed method using adipose tissue-derived
      stromal cells (ADSCs) and hydroxypropylmethylcellulose (HPMC) in building
      injectable tissue engineered cartilage in vivo. ADSCs from rabbit subcutaneous
      fatty tissue were cultured in chondrogenic differentiation medium and
      supplemented with transforming growth factor-beta1 (TGF-beta1) and basic
      fibroblast growth factor (bFGF). Histological, immunohistochemistry and RT-PCR
      analysis confirmed that the ADSCs differentiated into chondrocytes following
      induction. Induced ADSCs mixed with 15 % HPMC were injected into the subcutaneous
      tissue of nude mice and, after a period of 8 weeks, newly formed cartilage was
      observed at the site of injection. The ability of ADSCs cultured in the induction
      medium with TGF-beta1 and bFGF to differentiate into chondrocytes and construct
      new cartilage indicates that ADSCs are suitable for use as seed cells in
      cartilage tissue engineering. HPMC, according to its good water solubility and
      being able to transform from liquid to solid at body temperature, was found to be
      an ideal scaffold for tissue engineering. 

PMID- 24287611
TI  - Improved cosmetic activity by optimizing the Lithospermum erythrorhizon
      extraction process.
AB  - This study was conducted to expand the use of Lithospermum erythrorhizon, which
      is a good source of natural dye, in skin whitening and immune activation
      cosmetics. The goal was to provide cosmeceutical data about the extraction yield
      and shikonin contents of this plant by optimizing the ultrasonic extraction and
      high pressure extraction conditions. Under optimal extraction conditions, which
      consisted of 500 MPa for 60 min and 120 kHz for 90 min, 27.49 and 3.19 % (w/w) of
      the highest extraction yield and shikonin contents were obtained, compared to
      16.32 and 1.81 % from a conventional ethanol extract (EE) control. Hyaluronidase
      inhibition activity was measured as 44.24 % after adding 1.0 mg/ml of ethanol
      extract, but it was as high as 64.19 % when using extract produced by
      ultrasonication with high pressure extraction (UE + HPE). The MMP-1 expression
      levels from skin fibroblast cells (CCD-986sk) treated with or without UV
      irradiation were also lowered by as much as 110.6 % after adding 1.0 mg/ml of the
      UE + HPE extract, relative to 126.9 % from the EE. After UVA exposure,
      prostaglandin E2 production from RAW 264.7 was also lower, at 110.6 %, which also
      indicates that the extract from the UE + HPE process enhanced skin immune
      activation activities. For the skin whitening activity, tyrosinase inhibitory
      activity was observed at 67.15 % in the HPE + UE extract, which was ca. 20 %
      higher than that of the EE extract (57.48 %). To reduce melanin production in
      Clone M-3 cells, 79.5 % of the melanin production was estimated after adding 1.0
      mg/ml of the UE + HPE extract compared to that of the control (no treatment),
      which was similar to the 77.4 % result found in an ascorbic acid positive
      control. The highest shikonin secretion was conclusively obtained under the
      optimal conditions and resulted in a significant improvement of the cosmetic
      activities of L. erythrorhizon extracts. 

PMID- 24287612
TI  - Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in
      contracted collagen gels.
AB  - Knee osteoarthritis is a degenerative disease of diarthrodial joints.
      Biomechanical factors are considered as risk factors for the disease, the knee
      joint being normally subject to pressure. Some studies have examined the
      biomechanical environment of the knee joint in vitro. The aim of this study was
      to establish a culture model to mimic the knee joint environment. As a first
      step, synoviocytes induced contraction of three-dimensional collagen gels. Next,
      contracted collagen gels containing synoviocytes underwent cyclical compression
      ranging from 0 to 40 kPa at a frequency of 1.0 Hz for 1.5, 3, 6 and 12 h using
      the FX-4000CTM Flexercell((r)) Compression PlusTM System. RNA in collagen gels
      was extracted immediately after compression and mRNA expression levels of HAS
      genes were analyzed by quantitative RT-PCR. Culture medium was collected 48 h
      after compression and analyzed by agarose gel electrophoresis and cellulose
      acetate electrophoresis. Synoviocytes in contracted collagen gels were stimulated
      by cyclic compressive load. Long-term compressive stimulation led to the
      production of higher molecular weight hyaluronic acid, whereas, short-term,
      compressive stimulation increased the total amount of hyaluronic acid.
      Furthermore, mRNA expression levels of both HAS-1 and HAS-2 were significantly
      higher than without compression. Taken together, using this gel culture system,
      synoviocytes synthesized higher molecular weight hyaluronic acid and produced
      large quantities of hyaluronic acid through up-regulation of HAS gene expression.
      Therefore, the contracted collagen gel model will be a useful in vitro three
      dimensional model of the knee joint. 

PMID- 24287613
TI  - Monitoring of cellular behaviors by microcavity array-based single-cell
      patterning.
AB  - In this study, we describe a less invasive and rapid single-cell patterning
      technique for monitoring of cellular behaviors. To form a high-density grid
      pattern of living cells, single cells were firstly captured on a geometry
      controlled array pattern of 100,000 microcavities by applying negative pressure.
      The captured cells on the microcavities were immersed in an agarose solution and
      embedded in agarose gels. The high efficiency transfer of individual yeast cells
      (Saccharomyces cerevisiae) and diatom cells (Fistulifera sp.) onto agarose gels
      was successfully achieved in 20 min. The patterning process had no effect on the
      cell proliferation or division. These results indicate that this technique shows
      a dramatic increase in patterning efficiency compared to previous patterning
      technologies. Furthermore, it allows the long-term monitoring of diatom cell
      divisions for 24 h. Continuous long-term observation of single cells provides
      technological advantages for the successful acquisition of information to better
      understand cellular activities.

PMID- 24287614
TI  - Superconductivity in anti-post-Perovskite vanadium compounds.
AB  - Superconductivity, which is a quantum state induced by spontaneous gauge symmetry
      breaking, frequently emerges in low-dimensional materials. Hence, low
      dimensionality has long been considered as necessary to achieve high
      superconducting transition temperatures (TC). The recently discovered post
      perovskite (ppv) MgSiO3, which constitutes the Earth's lowermost mantle (D"
      layer), has attracted significant research interest due to its importance in
      geoscience. The ppv structure has a peculiar two-dimensional character and is
      expected to be a good platform for superconductivity. However, hereunto, no
      superconductivity has been observed in isostructural materials, despite extensive
      investigation. Here, we report the discovery of superconductivity with a maximum
      TC of 5.6 K in V3PnNx (Pn = P, As) phases with the anti-ppv structure, where the
      anion and cation positions are reversed with respect to the ppv structure. This
      discovery stimulates further explorations of new superconducting materials with
      ppv and anti-ppv structures. 

PMID- 24287616
TI  - A stimuli-responsive orthogonal supramolecular polymer network formed by metal
      ligand and host-guest interactions.
AB  - A stimuli-responsive supramolecular polymer network was constructed by the
      orthogonal assembly of metal-ligand interactions and host-guest interactions. 

PMID- 24287615
TI  - Hysteresis of ligand binding in CNGA2 ion channels.
AB  - Tetrameric cyclic nucleotide-gated (CNG) channels mediate receptor potentials in
      olfaction and vision. The channels are activated by the binding of cyclic
      nucleotides to a binding domain embedded in the C terminus of each subunit. Here
      using a fluorescent cGMP derivative (fcGMP), we show for homotetrameric CNGA2
      channels that ligand unbinding is ~50 times faster at saturating than at
      subsaturating fcGMP. Analysis with complex Markovian models reveals two pathways
      for ligand unbinding; the partially liganded open channel unbinds its ligands
      from closed states only, whereas the fully liganded channel reaches a different
      open state from which it unbinds all four ligands rapidly. Consequently, the
      transition pathways for ligand binding and activation of a fully liganded CNGA2
      channel differ from that of ligand unbinding and deactivation, resulting in
      pronounced hysteresis of the gating mechanism. This concentration-dependent
      gating mechanism allows the channels to respond to changes in the cyclic
      nucleotide concentration with different kinetics. 

PMID- 24287617
TI  - Interplay between chromatin-modifying enzymes controls colon cancer progression
      through Wnt signaling.
AB  - Cancer progression is associated with epigenetic alterations, such as changes in
      DNA methylation, histone modifications or variants incorporation. The p400
      ATPase, which can incorporate the H2A.Z variant, and the Tip60 histone
      acetyltransferase are interacting chromatin-modifying proteins crucial for the
      control of cell proliferation. We demonstrate here that Tip60 acts as a tumor
      suppressor in colon, since mice heterozygous for Tip60 are more susceptible to
      chemically induced preneoplastic lesions and adenomas. Strikingly, heterozygosity
      for p400 reverses the Tip60-dependent formation of preneoplastic lesions,
      uncovering for the first time pro-oncogenic functions for p400. By genome-wide
      analysis and using a specific inhibitor in vivo, we demonstrated that these
      effects are dependent on Wnt signaling which is antagonistically impacted by p400
      and Tip60: p400 directly favors the expression of a subset of Wnt-target genes
      and regulators, whereas Tip60 prevents beta-catenin acetylation and activation.
      Taken together, our data underline the physiopathological importance of
      interplays between chromatin-modifying enzymes in the control of cancer-related
      signaling pathways. 

PMID- 24287618
TI  - Gadolinium-binding cyclic hexapeptoids: synthesis and relaxometric properties.
AB  - Two new cyclic hexapeptoids incorporating N-carboxyethylglycine and N
      methoxyethylglycine residues are able to efficiently bind Gd(3+). Their
      thermodynamic stabilities and relaxivities have been assessed by (1)H
      relaxometric investigations. 

PMID- 24287619
TI  - Anterior cruciate ligament elasticity and force for flexion during the menstrual
      cycle.
AB  - BACKGROUND: A high occurrence of knee injuries have been observed in women during
      the menstrual cycle (MC). As a result, numerous studies have been conducted
      regarding knee ligament elasticity during the MC. Some researchers believe that
      since estrogen receptor b exists in ligaments and tendons in the knee, estrogen
      may modulate towards a state of laxity. However, increased tissue temperature
      also observed during the MC can predispose ligament and tendon laxness.
      Therefore, the purpose of this study was to assess in women the relationship
      between Estradiol (E2) serum concentrations and tissue temperature during the MC
      and their combined effect on knee laxity. MATERIAL AND METHODS: Ten non-athletic
      young healthy females, 18 to 30 years of age participated in the study. E2 serum
      concentrations, anterior cruciate ligament (ACL) elasticity, and force to flex
      the knee (FFK), knee flexion-extension hysteresis (KFEH) were assessed both at
      ambient temperature (22  degrees C) and after 38  degrees C warming. Testing was
      performed multiple times during the participant's MC, for one full MC. RESULTS:
      ACL elasticity was significantly higher (P<0.01) and FFK and KFEH were
      significantly lower (p<0.05) during ovulation when E2 levels were highest. ACL
      elasticity was still higher during ovulation after warming to 38  degrees C. But,
      the effects of MC on FFK and KFEH were reduced by tissue warming. CONCLUSIONS:
      ACL elasticity, FFK, and KFEH was affected not only by E2 but also tissue
      temperature. However, E2 had more impact on ACL elasticity while tissue
      temperature had more impact on FFK and KFEH at 38  degrees C warming.

PMID- 24287620
TI  - Absence of glucocorticoids augments stress-induced Mkp1 mRNA expression within
      the hypothalamic-pituitary-adrenal axis.
AB  - Stress-induced activation of hypothalamic paraventricular nucleus (PVN)
      corticotropin-releasing hormone (CRH) neurons trigger CRH release and synthesis.
      Recent findings have suggested that this process depends on the intracellular
      activation (phosphorylation) of ERK1/2 within CRH neurons. We have recently shown
      that the presence of glucocorticoids constrains stress-stimulated phosphorylation
      of PVN ERK1/2. In some peripheral cell types, dephosphorylation of ERK has been
      shown to be promoted by direct glucocorticoid upregulation of the MAP kinase
      phosphatase 1 (Mkp1) gene. In this study, we tested the hypothesis that
      glucocorticoids regulate Mkp1 mRNA expression in the neural forebrain (medial
      prefrontal cortex, mPFC, and PVN) and endocrine tissue (anterior pituitary) by
      subjecting young adult male Sprague-Dawley rats to various glucocorticoid
      manipulations with or without acute psychological stress (restraint). Restraint
      led to a rapid increase in Mkp1 mRNA within the mPFC, PVN, and anterior
      pituitary, and this increase did not require glucocorticoid activity. In contrast
      to glucocorticoid upregulation of Mkp1 gene expression in the peripheral tissues,
      we found that the absence of glucocorticoids (as a result of adrenalectomy)
      augmented basal mPFC and stress-induced PVN and anterior pituitary Mkp1 gene
      expression. Taken together, this study indicates that the presence of
      glucocorticoids may constrain Mkp1 gene expression in the neural forebrain and
      endocrine tissues. This possible constraint may be an indirect consequence of the
      inhibitory influence of glucocorticoids on stress-induced activation of ERK1/2, a
      known upstream positive regulator of Mkp1 gene transcription. 

PMID- 24287621
TI  - TNFRSF14 deficiency protects against ovariectomy-induced adipose tissue
      inflammation.
AB  - To elucidate the role of tumor necrosis factor receptor superfamily member 14
      (TNFRSF14) in metabolic disturbance due to loss of ovarian function, ovariectomy
      (OVX) was performed in TNFRSF 14-knockout mice. OVX increased fat mass and
      infiltration of highly inflammatory CD11c cells in the adipose tissue (AT), which
      was analyzed by flow cytometry, and resulted in disturbance of glucose
      metabolism, whereas TNFRSF14 deficiency attenuated these effects. TNFRSF14
      deficiency decreased recruitment of CD11c-expressing cells in AT and reduced the
      polarization of bone marrow-derived macrophages to M1. Upon engagement of LIGHT,
      a TNFRSF14 ligand, TNFRSF14 enhanced the expression of CD11c via generation of
      reactive oxygen species, suggesting a role of TNFRSF14 as a redox modulator.
      TNFRSF14 participated in OVX-induced AT inflammation via upregulation of CD11c,
      resulting in metabolic perturbation. TNFRSF14 could be used as a therapeutic
      target for the treatment of postmenopausal syndrome by reducing AT inflammation. 

PMID- 24287622
TI  - Nano-encapsulation of plitidepsin: in vivo pharmacokinetics, biodistribution, and
      efficacy in a renal xenograft tumor model.
AB  - PURPOSE: Plitidepsin is an antineoplasic currently in clinical evaluation in a
      phase III trial in multiple myeloma (ADMYRE). Presently, the hydrophobic drug
      plitidepsin is formulated using Cremophor(r), an adjuvant associated with
      unwanted hypersensitivity reactions. In search of alternatives, we developed and
      tested two nanoparticle-based formulations of plitidepsin, aiming to
      modify/improve drug biodistribution and efficacy. METHODS: Using
      nanoprecipitation, plitidepsin was loaded in polymer nanoparticles made of
      amphiphilic block copolymers (i.e. PEG-b-PBLG or PTMC-b-PGA). The
      pharmacokinetics, biodistribution and therapeutic efficacy was assessed using a
      xenograft renal cancer mouse model (MRI-H-121 xenograft) upon administration of
      the different plitidepsin formulations at maximum tolerated multiple doses (0.20
      and 0.25 mg/kg for Cremophor(r) and copolymer formulations, respectively).
      RESULTS: High plitidepsin loading efficiencies were obtained for both copolymer
      formulations. Considering pharmacokinetics, PEG-b-PBLG formulation showed lower
      plasma clearance, associated with higher AUC and Cmax than Cremophor(r) or PTMC-b
      PGA formulations. Additionally, the PEG-b-PBLG formulation presented lower liver
      and kidney accumulation compared with the other two formulations, associated with
      an equivalent tumor distribution. Regarding the anticancer activity, all
      formulations elicited similar efficacy profiles, as compared to the Cremophor(r)
      formulation, successfully reducing tumor growth rate. CONCLUSIONS: Although the
      nanoparticle formulations present equivalent anticancer activity, compared to the
      Cremophor(r) formulation, they show improved biodistribution profiles, presenting
      novel tools for future plitidepsin-based therapies.

PMID- 24287623
TI  - Thermodynamic and fluorescence analyses to determine mechanisms of IgG1
      stabilization and destabilization by arginine.
AB  - PURPOSE: To investigate mechanisms governing the stabilization and
      destabilization of immunoglobulin (IgG1) by arginine (Arg). METHODS: The effects
      of Arg on the aggregation/degradation, thermodynamic stability, hydrophobicity,
      and aromatic residues of IgG1 were respectively investigated by size-exclusion
      chromatography, differential scanning calorimetry, probe fluorescence, and
      intrinsic fluorescence. RESULTS: Arg monohydrochloride (Arg-HCl) suppressed IgG1
      aggregation at near-neutral pH, but facilitated aggregation and degradation at
      acidic pH or at high storage temperature. Equimolar mixtures of Arg and aspartic
      acid (Asp) or glutamic acid (Glu) suppressed aggregation without facilitating
      degradation even at high temperature. Arg-HCl decreased the thermodynamic
      stability of IgG1 by enthalpic loss, which was counteracted by using Asp or Glu
      as a counterion for Arg. The suppression of aggregation by Arg-HCl was well
      correlated with the decrease in hydrophobicity of IgG1. The intrinsic
      fluorescence of IgG1 was unaffected by Arg-HCl. CONCLUSIONS: Suppression of IgG1
      aggregation can be attributed to the interaction between Arg and hydrophobic
      residues; on the other hand, facilitation of aggregation and degradation is
      presumably due to the interaction between Arg and some acidic residues, which
      could be competitively inhibited by simultaneously adding either Asp or Glu.

PMID- 24287625
TI  - Antimicrobial drugs encapsulated in fibrin nanoparticles for treating microbial
      infested wounds.
AB  - PURPOSE: In vitro evaluation of antibacterial and antifungal drugs encapsulated
      fibrin nanoparticles to prove their potential prospect of using these
      nanocomponent for effective treatment of microbial infested wounds. METHODS:
      Surfactant-free oil-in-water emulsification-diffusion method was adopted to
      encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole)
      in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross
      linking to synthesize drug loaded fibrin nanoparticles. RESULTS: Ciprofloxacin
      loaded fibrin nanoparticles (CFNPs) showed size range of 253 +/- 6 nm whereas
      that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260 +/- 10 nm.
      Physico chemical characterizations revealed the firm integration of antimicrobial
      drugs within fibrin nanoparticles. Drug release studies performed at
      physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole
      while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of
      fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded
      systems independently showed good antibacterial activity against Escherichia coli
      (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against
      Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded
      nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and
      showed adequate cell viability. CONCLUSION: The efficacies of both CFNPs and
      FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated
      in vitro suggesting its potential use for treating microbial infested wounds
      (diabetic foot ulcer).

PMID- 24287626
TI  - Who needs selection bias?

PMID- 24287624
TI  - A novel three-dimensional large-pore mesoporous carbon matrix as a potential
      nanovehicle for the fast release of the poorly water-soluble drug, celecoxib.
AB  - PURPOSE: A novel mesocellular carbon foam (MSU-FC) with a large pore size and a
      three-dimensional porous structure for the oral delivery of poorly water-soluble
      drugs was prepared. The goal of this study was to improve in vitro dissolution
      and in vivo absorption of celecoxib (CEB), a model drug, by means of novel carbon
      based nanoparticles prepared from the MSU-FC matrix. METHODS: The MSU-FC matrix
      was synthesized by an inverse replica templating method using mesocellular silica
      template. A solvent immersion/evaporation method was used to load the drug
      molecules. The drug-loaded nanoparticles were characterized for morphology,
      surface area, particle size, mesoporous structure, crystallinity, solubility and
      dissolution. The effect of MSU-FC on cell viability was measured using the MTT
      conversion assay. Furthermore, the oral bioavailability of CEB-loaded MSU-FC in
      fasted rats was compared with that of the marketed product. RESULTS: Our results
      demonstrate that CEB incorporation into the prepared MSU-FC resulted in an
      approximately 9-fold increase in aqueous solubility in comparison with
      crystalline CEB. MSU-FC produced accelerated immediate release of CEB in
      comparison with crystalline CEB (pure CEB powder or marketed formulation) and the
      drug-loaded conventional mesoporous carbon particles. The relative
      bioavailability of CEB for CEB-loaded MSU-FC was 172%. In addition, MSU-FC
      nanoparticles exhibited very low toxicity. CONCLUSIONS: The MSU-FC nanomatrix has
      been shown to be a promising drug delivery vehicle for improving the dissolution
      and biopharmaceutical characteristics of poorly water-soluble drugs.

PMID- 24287627
TI  - Novel self-assembly endows human serum albumin nanoparticles with an enhanced
      antitumor efficacy.
AB  - Protein-based nanomedicine plays an important role in tumor chemotherapy due to
      their merits in bioavailability, biocompatibility, biodegradability, and low
      toxicity. In this study, we developed a novel method of preparing human serum
      albumin (HSA) nanoparticles for targeted delivery of paclitaxel (PTX) to tumors.
      HSA-PTX nanoparticles (NPs-PTX) were fabricated via unfolding of HSA in
      appropriate solution to expose more hydrophobic domains and consequent self
      assembling into nanoparticles with added PTX. Via this self-assembly method, a
      desirable particle size (around 120 nm), a high drug loading (>20%), and a high
      encapsulation efficiency (near 100%) were obtained. PTX dispersed as an amorphous
      state in NPs-PTX and the secondary structures of HSA were maintained. In a
      cytotoxicity study, NPs-PTX displayed an enhanced cytotoxicity in MCF-7 and A549
      cells. Confocal microscopy and flow cytometry revealed that the uptake of NPs-PTX
      was mediated by secreted protein acidic and rich in cysteine and "caveolar"
      transport. In H22 tumor-bearing mice, NPs-PTX displayed an increasing and
      everlasting tumor distribution, leading to slower tumor growth and longer mice
      survival than PTX. Therefore, this novel self-assembly method offers a much
      easier method to prepare PTX nanoparticles, provides better antitumor efficacy in
      vitro and in vivo, and more importantly, sets up a delivery platform for other
      hydrophobic drugs to improve their effectiveness in cancer therapy.

PMID- 24287628
TI  - Novel fungus-titanate bio-nanocomposites as high performance adsorbents for the
      efficient removal of radioactive ions from wastewater.
AB  - Reclaimable adsorbents have a critical application in the adsorption of
      radioactive materials. In this study, the novel bio-nanocomposites comprising
      fungi and titanate nanotubes are successfully synthesized by a simple and low
      cost method. Morphological characterizations and composite mechanism analysis
      confirm that the composites are sufficiently stable to avoid dust pollution
      resulting from the titanate nanomaterials. Adsorption experiments demonstrate
      that the bio-nanocomposites are efficient adsorbents with a saturated sorption
      capacity as high as 120 mg g(-1) (1.75 meq. g(-1)) for Ba(2+) ions. The results
      suggest that the bio-nanocomposites can be used as promising radioactive
      adsorbents for removing radioactive ions from water caused by nuclear leakage. 

PMID- 24287629
TI  - A truncated Wnt7a retains full biological activity in skeletal muscle.
AB  - Wnt signaling has essential roles during embryonic development and tissue
      homoeostasis. Wnt proteins are post-translationally modified and the attachment
      of a palmitate moiety at two conserved residues is believed to be a prerequisite
      for the secretion and function of Wnt proteins. Here we demonstrate that a
      mammalian Wnt protein can be fully functional without palmitoylation. We generate
      a truncated Wnt7a variant, consisting of the C-terminal 137 amino acids lacking
      the conserved palmitoylation sites and show that it retains full biological
      activity in skeletal muscle. This includes binding to and signaling through its
      receptor Fzd7 to stimulate symmetric expansion of satellite stem cells by
      activating the planar-cell polarity pathway and inducing myofibre hypertrophy by
      signaling through the AKT/mTOR pathway. Furthermore, this truncated Wnt7a shows
      enhanced secretion and dispersion compared with the full-length protein.
      Together, these findings open important new avenues for the development of Wnt7a
      as a treatment for muscle-wasting diseases and have broad implications for the
      therapeutic use of Wnts as biologics. 

PMID- 24287630
TI  - Cellphone-based devices for bioanalytical sciences.
AB  - During the last decade, there has been a rapidly growing trend toward the use of
      cellphone-based devices (CBDs) in bioanalytical sciences. For example, they have
      been used for digital microscopy, cytometry, read-out of immunoassays and lateral
      flow tests, electrochemical and surface plasmon resonance based bio-sensing,
      colorimetric detection and healthcare monitoring, among others. Cellphone can be
      considered as one of the most prospective devices for the development of next
      generation point-of-care (POC) diagnostics platforms, enabling mobile healthcare
      delivery and personalized medicine. With more than 6.5 billion cellphone
      subscribers worldwide and approximately 1.6 billion new devices being sold each
      year, cellphone technology is also creating new business and research
      opportunities. Many cellphone-based devices, such as those targeted for diabetic
      management, weight management, monitoring of blood pressure and pulse rate, have
      already become commercially-available in recent years. In addition to such
      monitoring platforms, several other CBDs are also being introduced, targeting
      e.g., microscopic imaging and sensing applications for medical diagnostics using
      novel computational algorithms and components already embedded on cellphones.
      This report aims to review these recent developments in CBDs for bioanalytical
      sciences along with some of the challenges involved and the future opportunities.

PMID- 24287631
TI  - Paper-based device for rapid typing of secondary human blood groups.
AB  - We report the use of bioactive paper for typing of secondary human blood groups.
      Our recent work on using bioactive paper for human blood typing has led to the
      discovery of a new method for identifying haemagglutination of red blood cells.
      The primary human blood groups, i.e., ABO and RhD groups, have been successfully
      typed with this method. Clinically, however, many secondary blood groups can also
      cause fatal blood transfusion accidents, despite the fact that the
      haemagglutination reactions of secondary blood groups are generally weaker than
      those of the primary blood groups. We describe the design of a user-friendly
      sensor for rapid typing of secondary blood groups using bioactive paper. We also
      present mechanistic insights into interactions between secondary blood group
      antibodies and red blood cells obtained using confocal microscopy.
      Haemagglutination patterns under different conditions are revealed for
      optimization of the assay conditions. 

PMID- 24287632
TI  - Analysis of cyathane-type diterpenoids from Cyathus striatus and Hericium
      erinaceus by high-resolution MALDI MS imaging.
AB  - Fungal secondary metabolites in both fruiting bodies and pellets from submerged
      cultures of basidiomycetes were analyzed by atmospheric pressure matrix-assisted
      laser desorption/ionization-mass spectrometry imaging at a lateral resolution of
      15 MUm, a mass resolution of 140,000 at m/z 200 and a mass accuracy of better
      than 2 ppm. The striatals A, B, C, and D, and a number of erinacine type
      metabolites were detected in the basidiomycetes Cyathus striatus and Hericium
      erinaceus, respectively. The two fungi were selected as model species, as they
      are well-known for efficient production of terpenoid secondary metabolites with
      interesting biological activities, e.g., antibacterial, fungicidal, cytotoxic
      properties, and stimulating effects on nerve growth factor synthesis. The
      localization of metabolites revealed a mostly homogeneous distribution of the
      striatals in the pellets of C. striatus, while a concentration gradient,
      increasing to the center, was observed in the pellets of H. erinaceus. A mostly
      homogeneous distribution of metabolites was also found in the fruiting body of H.
      erinaceus. 

PMID- 24287633
TI  - Highly sensitive determination of ssDNA and real-time sensing of nuclease
      activity and inhibition based on the controlled self-assembly of a 9,10
      distyrylanthracene probe.
AB  - We report here a fluorescent biosensor for highly sensitive determination of
      single-stranded DNA (ssDNA) with remarkable fluorescence enhancement and label
      free sensing of S1 nuclease activity and inhibition in real time based on ssDNA
      controlled self-assembly of a 9,10-distyrylanthracene (DSA) probe with the
      aggregation-induced emission (AIE) property, thereby avoiding a sophisticated
      fabrication process and aggregation-caused quenching (ACQ) effect. Compared with
      previous technologies, this assay has some advantages. First, since the DSA probe
      can be synthesized through a simple and effective synthetic route and the sensing
      technology adopts the unlabelled ssDNA, this biosensor shows advantages of
      simplicity and cost efficiency. Besides, for the determination of ssDNA, S1
      nuclease, and inhibitor, the DSA-based probe provides high sensitivity and a good
      linear relationship due to the AIE property. As a result, we determined the DNA
      24-mer concentration as low as 150 pM, and we are able to detect ssDNA lengths
      with a linear range from 6mer to 24mer (R = 0.998) as well as DNA 24-mer
      concentrations with a linear range from 0 to 200 nM (R = 0.998) and S1 nuclease
      concentrations with a linear range from 6 to 32 U ml(-1) (R = 0.995),
      respectively. Moreover, the fluorescent intensity with various concentrations of
      S1 nuclease becomes highly discriminating after 3-16 min. Thus, it is possible to
      detect nuclease activity within 3-16 min, which demonstrates another advantage of
      a quick response of the present biosensor system. 

PMID- 24287634
TI  - Determination of free cortisol and free cortisone in human urine by on-line
      turbulent flow chromatography coupled to fused-core chromatography-tandem mass
      spectrometry (TFC-HPLC-MS/MS).
AB  - Urinary free cortisol and urinary free cortisone are decisive markers for the
      diagnosis of syndromes related to the dysfunction of the adrenal gland or to
      evaluate certain enzymatic disorders. Here, we present a new method, designed for
      routine laboratory use, which enables quick determination of these analytes with
      minor sample workup. Turbulent flow chromatography shortens sample preparation,
      and connection to a fused-core particle-packed column (rugged amide-embedded C18
      phase) permits a rapid and effective separation of the analytes, as well as
      additional separation from other related and isobaric compounds present in urine.
      Urinary isobaric compounds were successfully identified. The method requires only
      100 MUl of urine supernatant per sample. The total time between injections is 9.5
      min. The solvents used for both turbulent and analytical chromatography are water
      and methanol, and the relatively low flows needed during the method resulted in
      an extended life of the columns. Linearity showed a R (2) > 0.994. Limit of
      detection and limit of quantification are 0.5 and 1.0 ng/ml for cortisone and 1.0
      and 2.0 ng/ml for cortisol. Recoveries ranged from 99.7 to 109.1 % for cortisone
      and from 98.7 to 102.9 % for cortisol. Accuracy values (relative errors) for
      intra- and inter-assay experiments were always below 8 %, whereas precision
      (percent CV) ranged from 3.7 to 10.7 %. No matrix effects were detected during
      the validation process. The reproducibility for each analyte's retention time was
      excellent, with a coefficient of variation always below 0.2 %. The final
      validation step included the study of urine samples from healthy children and
      from children previously diagnosed with corticoidal disorders. The high
      selectivity achieved enables quick data handling. 

PMID- 24287635
TI  - Bioactivity screening and mass spectrometric confirmation for the detection of
      PPARdelta agonists that increase type 1 muscle fibres.
AB  - Sensitive and robust bioassays able to detect nuclear receptor activation are
      very useful for veterinary and doping control, pharmaceutical industry and
      environmental scientists. Here, we used bioassays based on human leukemic
      monocyte lymphoma U937 and human liver hepatocellular carcinoma HepG2 cell lines
      to detect the ligand-induced activation of the peroxisome proliferator-activated
      receptor delta (PPARdelta). Exposure of U937 cells to the PPARdelta agonist
      GW501516 resulted in a marked increase in mRNA expression of the PPARdelta target
      gene Angptl4 which was quantified by qRT-PCR analysis. Exposure of HepG2 cells
      transiently transfected with a PPARdelta expression plasmid and a PPAR-response
      element-driven luciferase reporter plasmid to PPARdelta agonists GW501516,
      GW610742 and L-165041 resulted in clear dose-response curves. Although the qRT
      PCR resulted in higher fold inductions, the luciferase assay with transfected
      HepG2 cells is cheaper and quicker and about ten times more sensitive to GW501516
      compared to analysis of Angptl4 mRNA expression in U937 cells by qRT-PCR. The
      HepG2-based luciferase assay was therefore used to screen GW501516-spiked
      supplements and feed and water samples. After liquid extraction and clean-up by
      solid phase extraction using a weak anion exchange column, extracts were screened
      in the HepG2 bioassay followed by confirmation with a newly developed UPLC-MS/MS
      method, using two transitions for each compound, i.e., for GW501516,
      454.07>188.15 (collision energy (CE) 46 V) and 454.07>257.08 (CE 30 V); for
      GW610742, 472.07>206.2 (CE 48 V) and 472.07>275.08 (CE 30 V); and for L-165041,
      401.2>193.15 (CE 26 V) and 401.2>343.2 (CE 20 V). 

PMID- 24287636
TI  - Upper extremity reconstruction in non-traumatic spinal cord injuries: An under
      recognized opportunity.
AB  - OBJECTIVE: This study reviews the usefulness of surgical improvement of arm and
      hand function in patients with non-traumatic spinal cord injury who differ
      significantly from individuals with post-traumatic tetraplegia with respect to
      age, injury pattern, gender and socio-economic factors. DESIGN: Case series.
      Tests were conducted preoperatively and 12 months postoperatively. PATIENTS: The
      results of 14 upper extremity reconstructions in 11 patients (7 women, 4 men)
      with spinal cord injury, mean age at injury 49 years (standard deviation (SD)
      12), were reviewed. METHODS: Key pinch strength, grip strength and first web
      space opening were recorded pre- and post-operatively in all patients, 5 patients
      (7 hands) were evaluated prospectively regarding manual dexterity. RESULTS: All
      parameters were significantly improved. Strength of key pinch increased from 0.3
      kg in 1 case and zero in 10 cases to a mean of 1.6 kg (SD 0.9). Mean grip
      strength increased from 0 to 3.2 kg (SD 4.5). Maximal distance between thumb and
      index increased from 2.1 cm (SD 4.1) to 6.4 cm (SD 4.4). Manual dexterity
      increased. CONCLUSION: Individuals with stable non-traumatic tetraplegia benefit
      from surgical rehabilitation of their upper extremities. The number of non
      traumatic spinal cord injuries is likely to increase as lifespan increases
      worldwide, and further research into the functional rehabilitation of this
      population will therefore become increasingly relevant.

PMID- 24287637
TI  - Forensic electrochemistry: the electroanalytical sensing of synthetic cathinone
      derivatives and their accompanying adulterants in "legal high" products.
AB  - The production and abuse of new psychoactive substances, known as "legal highs"
      which mimic traditional drugs of abuse is becoming a global epidemic. Traditional
      analytical methodologies exist which can provide confirmatory analysis but there
      is a requirement for an on-the-spot analytical screening tool that could be used
      to determine whether a substance, or sample matrix contains such legal, or
      formally "legal highs". In this paper the electrochemical sensing of (+/-)
      methcathinone and related compounds at a range of commercially available
      electrode substrates is explored. We demonstrate for the first time that this
      class of "legal highs" are electrochemically active providing a novel sensing
      protocol based upon their electrochemical oxidation. Screen-printed graphite
      sensing platforms are favoured due to their proven ability to be mass-produced
      providing large numbers of reliable and reproducible electrode sensing platforms
      that preclude the requirement of surface pre-treatment such as mechanical
      polishing as is the case in the use of solid/re-usable electrode substrates.
      Additionally they hold potential to be used on-site potentially being the basis
      of an on-site legal high screening device. Consequently the electroanalytical
      sensing of (+/-)-methcathinone (3a), (+/-)-4'-methylmethcathinone [3b, 4-MMC, (+/
      )-mephedrone] and (+/-)-4'-methyl-N-ethylcathinone (3c, 4-MEC) is explored using
      screen-printed sensing platforms with the effect of pH explored upon the
      analytical response with their analytical efficiency evaluated towards the target
      legal highs. Interesting at pH values below 6 the voltammetric response
      quantitatively changes from that of an electrochemically irreversible response to
      that of a quasi-reversible signature which can be used analytically. It is
      demonstrated for the first time that the electroanalytical sensing of (+/-)
      methcathinone (3a), (+/-)-mephedrone (3b) and 4-MEC (3c) are possible with
      accessible linear ranges found to correspond to 16-200 MUg mL(-1) for 3a (at pH
      12) and 16-350 MUg mL(-1) for both 3b and 3c in pH 2, with limits of detection
      (3sigma) found to correspond to 44.5, 39.8 and 84.2 MUg mL(-1) respectively.
      Additionally adulterants that are commonly incorporated into cathinone legal
      highs are electrochemically explored at both pH 2 and 12.

PMID- 24287638
TI  - Osteolysis in cemented total hip arthroplasty involving the OptiPlug cement
      restrictor: more than an incident?
AB  - The case report of a severe osteolytic reaction surrounding the OptiPlug cement
      restrictor in a 74-year-old male patient initiated a retrospective case series
      and closer investigation into the OptiPlug and its active compound, PolyActive.
      Not only did we find several cases of severe osteolysis in our own study
      population of 284 patients, several articles have lately described potential
      harmful side effects of the PolyActive material in humans. Although none of the
      articles have been based on large databases, we cannot guarantee the safety of
      this product. More research would help in our understanding of this phenomenon.
      Until then, we cannot recommend the use of the OptiPlug cement restrictor. 

PMID- 24287639
TI  - Comparison of endoscopic papillary balloon dilation and sphincterotomy in young
      patients with CBD stones and gallstones.
AB  - BACKGROUND AND AIMS: Endoscopic biliary sphincterotomy (EBS) results in permanent
      loss of sphincter function and its long-term complications are unknown.
      Endoscopic papillary balloon dilation (EPBD) is an alternative procedure that
      preserves sphincter function, although it is associated with a higher risk of
      pancreatitis than is EBS. The aim of this study was to evaluate the safety and
      outcomes of EPBD with limited indications for removal of common bile duct (CBD)
      stones combined with gallstones in patients younger than 40 years. METHODS: Young
      (age < 40 years) patients who had CBD stones combined with gallstones on imaging
      studies were enrolled in this study. A total of 132 patients were randomly
      divided into the EPBD group (n = 62) or the EBS group (n = 70) for extraction of
      CBD stones. The ballooning size of EPBD ranged from 6 to 10 mm. RESULTS: Complete
      bile duct clearance was achieved in 98.4 % (61/62) of the EPBD group and 100 %
      (70/70) of the EBS group. Mechanical lithotripsy was required in 8.1 % (5/62) of
      the EPBD group and 8.6 % (6/70) of the EBS group. The early complication rates
      were 8.1 % (5/62) (five pancreatitis) in the EPBD group and 11.4 % (8/70) (five
      [7.1 %] pancreatitis, two bleeding and one perforation) in the EBS group. The
      recurrence rates of CBD stones were 1.6 % (1/62) in the EPBD group and 5.7 %
      (4/70) in the EBS group. CONCLUSIONS: EPBD with limited indications was safe and
      effective as EBS for removal of CBD stones combined with gallstones in young
      patients who had a longer life expectancy.

PMID- 24287640
TI  - Children with cystic fibrosis have prolonged chemical clearance of acid reflux
      compared to symptomatic children without cystic fibrosis.
AB  - OBJECTIVES: Few studies compare gastroesophageal reflux (GER) parameters of
      cystic fibrosis (CF) children and symptomatic non-CF children. We aimed to
      compare the impedance-pH (IMP-pH) parameters for these two groups and to test the
      hypothesis that prolonged acid exposure in CF patients is due to delayed chemical
      clearance (CC). METHODS: IMP-pH tracings from 16 CF children (median 8.2 years)
      and 16 symptomatic non-CF children (median 8.3 years) were analyzed. Software was
      used to generate IMP-pH reports and parameter data were extracted. IMP-pH was
      used to calculate the mean CC for each patient. RESULTS: pH studies showed no
      difference in acid GER (AGER) frequency (p = 0.587); however, mean AGER duration,
      duration of longest AGER, AGER index, and DeMeester scores were all significantly
      higher for CF patients. IMP showed no difference in GER frequency [neither acidic
      (p = 0.918) nor non-acidic (p = 0.277)], but total bolus clearance was more
      efficient in CF patients (p = 0.049). A larger percentage of total GER reached
      the proximal esophagus in non-CF children (p = 0.039). Analyses of two-phase AGER
      episodes showed that these events were more acidic (p = 0.003) and the CC phase
      was significantly prolonged in the CF cohort (p = 0.001). CONCLUSIONS: Compared
      to symptomatic non-CF children, CF children do not have more frequent reflux.
      Actually, they have better bolus clearance efficiency following reflux and may
      even have better control over the number of GER episodes that reach the proximal
      esophagus. CC of AGER, however, is significantly prolonged in the CF cohort,
      likely due to hyperacidity of refluxed gastric contents.

PMID- 24287641
TI  - Intestinal and peripheral fibrinogen-like protein 2 expression in inflammatory
      bowel disease.
AB  - BACKGROUND: Fibrinogen-like protein 2 (FGL2), a new member of the fibrinogen-like
      family, has recently been identified as a novel immunosuppressive molecule. AIM:
      The purpose of this work was to investigate intestinal and peripheral expression
      of FGL2 in patients with inflammatory bowel disease (IBD), mainly ulcerative
      colitis (UC) and Crohn's disease (CD). METHODS: FGL2 expression in mucosal
      biopsies from three groups (UC group (n = 61), CD group (n = 54), and controls
      group (n = 35)) was detected by immunohistochemistry. Concentrations of FGL2 in
      plasma from 50 UC patients, 45 CD patients, and 30 controls were analyzed by
      enzyme-linked immunosorbent assay. Western blot of FGL2 protein and real-time
      fluorescent quantitative PCR of FGL2 mRNA expression by peripheral mononuclear
      cells was performed. Correlations of FGL2 expression with disease type, activity,
      and location, and with measured laboratory data, including C-reactive protein
      (CRP) and erythrocyte sedimentation rate (ESR), were examined. RESULTS:
      Intestinal and peripheral FGL2 protein data showed that FGL2 expression was
      significantly up-regulated in both UC and CD patients compared with controls (P <
      0.001). Expression of FGL2 was higher in UC and CD patients with active disease
      than in those with inactive disease (P < 0.001). Moreover, FGL2 mRNA expression
      was significantly higher in patients with active disease than in those with
      inactive disease (P < 0.050). Expression of FGL2 protein was correlated with
      disease activity indices, CRP levels, and ESR levels. CONCLUSION: Expression of
      FGL2 was up-regulated in IBD patients with active disease. Measurement of FGL2
      may be used as a helpful biomarker for understanding immunopathogenesis and for
      assessment of IBD.

PMID- 24287642
TI  - A novel anchoring system for colonic stents: a pilot in vivo study in a porcine
      model.
AB  - BACKGROUND: Colorectal stents have a proven role in colorectal cancer as
      palliative care or a bridge to surgery. However, their efficacy and anchoring to
      the tissue varies according to stent design with stent migration rates up to 50
      %. We present preliminary in vivo results of a new end-luminal anchoring system
      for stent fixation to the rectal canal. The aim was to assess the efficacy and
      safety of the stent using the anchoring system while subjecting the device to
      daily abdominal pressures related to daily activities in a porcine animal model.
      METHODS: Ex vivo anatomical and physical studies were performed to improve the
      system's structure and safety. Four female pigs were followed for the acute and
      chronic (16 weeks) period. Two animals were euthanized and underwent en-bloc
      pelvic visceral excision and histopathological examination. Device fixation time,
      animal behavior, device patency, anoscopic examination and histopathological
      features were assessed. RESULTS: Mean anchoring time was 13.83 weeks (standard
      error +/- 1.38 weeks). One of the animals experienced early device expulsion with
      no complications. No obstruction was noted in any of the animals. Macroscopic
      examination revealed mild focal submucosal scarring in one animal and a normal
      examination in the other. Hematoxylin and eosin staining revealed mucosal
      ulceration and mixed inflammatory cell infiltrate, with no signs of granulomata,
      foreign body giant cell reaction or microabscess formation. CONCLUSIONS: A novel
      fixation device designed for long-term intrarectal implantation was well
      tolerated and maintained anal canal patency without migration. Larger studies are
      needed before its implementation in humans.

PMID- 24287644
TI  - Rh-catalyzed allylic C-F bond activation: the stereoselective synthesis of
      trisubstituted monofluoroalkenes and a mechanism study.
AB  - Rhodium-catalyzed allylic C-F bond activation via oxidative addition was found to
      be a promising approach for the conversion of allylic difluoro-homoallylic
      alcohols into trisubstituted monofluoroalkenes in good yields with excellent
      stereoselectivity. The mechanism study shows that C-F bond activation via
      oxidative addition is involved and PPh3 is responsible for the excellent
      stereoselectivity. 

PMID- 24287643
TI  - Cell electrofusion using nanosecond electric pulses.
AB  - Electrofusion is an efficient method for fusing cells using short-duration high
      voltage electric pulses. However, electrofusion yields are very low when fusion
      partner cells differ considerably in their size, since the extent of
      electroporation (consequently membrane fusogenic state) with conventionally used
      microsecond pulses depends proportionally on the cell radius. We here propose a
      new and innovative approach to fuse cells with shorter, nanosecond (ns) pulses.
      Using numerical calculations we demonstrate that ns pulses can induce selective
      electroporation of the contact areas between cells (i.e. the target areas),
      regardless of the cell size. We then confirm experimentally on B16-F1 and CHO
      cell lines that electrofusion of cells with either equal or different size by
      using ns pulses is indeed feasible. Based on our results we expect that ns pulses
      can improve fusion yields in electrofusion of cells with different size, such as
      myeloma cells and B lymphocytes in hybridoma technology. 

PMID- 24287645
TI  - A brief history of Frankia and actinorhizal plants meetings.

PMID- 24287646
TI  - Micromonospora is a normal occupant of actinorhizal nodules.
AB  - Actinorhizal plants have been found in eight genera belonging to three orders
      (Fagales, Rosales and Cucurbitales). These all bear root nodules inhabited by
      bacteria identified as the nitrogen-fixing actinobacterium Frankia. These nodules
      all have a peripheral cortex with enlarged cells filled with Frankia hyphae and
      vesicles. Isolation in pure culture has been notoriously difficult, due in a
      large part to the growth of fast-growing contaminants where, it was later found,
      Frankia was slow-growing. Many of these contaminants, which were later found to
      be Micromonospora, were obtained from Casuarina and Coriaria. Our study was aimed
      at determining if Micromonospora were also present in other actinorhizal plants.
      Nodules from Alnus glutinosa, Alnus viridis, Coriaria myrtifolia, Elaeagnus x
      ebbingei, Hippophae rhamnoides, Myrica gale and Morella pensylvanica were tested
      and were all found to contain Micromonospora isolates. These were found to belong
      to mainly three species: Micromonospora lupini, Micromonospora coriariae and
      Micromonospora saelicesensis. Micromonospora isolates were found to inhibit some
      Frankia strains and to be innocuous to other strains.

PMID- 24287647
TI  - First report on the occurrence of the uncultivated cluster 2 Frankia
      microsymbionts in soil outside the native actinorhizal host range area.
AB  - The occurrence of uncultivated Frankia was evaluated in Tunisian soils by a plant
      trapping assay using Coriaria myrtifolia seedlings. Despite the lack of this
      compatible host plant for more than two centuries, soil-borne Frankia cells were
      detected in one sampled soil as shown by the development of root nodules on 2
      year-old seedlings. Based on glnA sequences, Tunisian trapped Frankia strains
      belong to the uncultivated cluster 2 strains that associate with other Coriaria
      species and also with Ceanothus, Datisca and Rosaceae actinorhizal species. This
      is the first report on the occurrence of Frankia cluster 2 strains in soils from
      areas lacking compatible host plant groups.

PMID- 24287648
TI  - Effect of salt stress on the physiology of Frankia sp strain CcI6.
AB  - Actinorhizal plants are able to overcome saline soils and reclaim land. Frankia
      sp strain CcI6 was isolated from nodules of Casuarina cunninghamiana found in
      Egypt. Phylogenetic analysis of Frankia sp. strain CcI6 revealed that the strain
      is closely related to Frankia sp. strain CcI3. The strain displays an elevated
      level of NaCl tolerance. Vesicle production and nitrogenase activity were also
      influenced by NaCl.

PMID- 24287649
TI  - Structural and gene expression analyses of uptake hydrogenases and other proteins
      involved in nitrogenase protection in Frankia.
AB  - The actinorhizal bacterium Frankia expresses nitrogenase and can therefore
      convert molecular nitrogen into ammonia and the by-product hydrogen. However,
      nitrogenase is inhibited by oxygen. Consequently, Frankia and its actinorhizal
      hosts have developed various mechanisms for excluding oxygen from their nitrogen
      containing compartments. These include the expression of oxygen-scavenging uptake
      hydrogenases, the formation of hopanoid-rich vesicles, enclosed by multi-layered
      hopanoid structures, the lignification of hyphal cell walls, and the production
      of haemoglobins in the symbiotic nodule. In this work, we analysed the expression
      and structure of the so-called uptake hydrogenase (Hup), which catalyses the in
      vivo dissociation of hydrogen to recycle the energy locked up in this 'waste'
      product. Two uptake hydrogenase syntons have been identified in Frankia: synton 1
      is expressed under freeliving conditions while synton 2 is expressed during
      symbiosis. We used qPCR to determine synton 1 hup gene expression in two Frankia
      strains under aerobic and anaerobic conditions. We also predicted the 3D
      structures of the Hup protein subunits based on multiple sequence alignments and
      remote homology modelling. Finally, we performed BLAST searches of genome and
      protein databases to identify genes that may contribute to the protection of
      nitrogenase against oxygen in the two Frankia strains. Our results show that in
      Frankia strain ACN14a, the expression patterns of the large (HupL1) and small
      (HupS1) uptake hydrogenase subunits depend on the abundance of oxygen in the
      external environment. Structural models of the membrane-bound hydrogenase
      subunits of ACN14a showed that both subunits resemble the structures of known
      [NiFe] hydrogenases (Volbeda et al. 1995), but contain fewer cysteine residues
      than the uptake hydrogenase of the Frankia DC12 and Eu1c strains. Moreover, we
      show that all of the investigated Frankia strains have two squalene hopane
      cyclase genes (shc1 and shc2). The only exceptions were CcI3 and the symbiont of
      Datisca glomerata, which possess shc1 but not shc2. Four truncated haemoglobin
      genes were identified in Frankia ACN14a and Eu1f, three in CcI3, two in EANpec1
      and one in the Datisca glomerata symbiont (Dg).

PMID- 24287650
TI  - Codon-optimized antibiotic resistance gene improves efficiency of transient
      transformation in Frankia.
AB  - Frankia is a unique actinobacterium having abilities to fix atmospheric
      dinitrogen and to establish endosymbiosis with trees, but molecular bases
      underlying these interesting characteristics are poorly understood because of a
      lack of stable transformation system. Extremely high GC content of Frankia genome
      (more than 70 percent) can be a hindrance to successful transformation. We
      generated a synthetic gentamicin resistance gene whose codon usage is optimized
      to Frankia (fgmR) and evaluated its usefulness as a selection marker using a
      transient transformation system. Success rate of transient transformation and
      cell growth in selective culture were significantly increased by use of fgmR
      instead of a native gentamicin resistance gene, suggesting that codon
      optimization improved translation efficiency of the marker gene and increased
      antibiotic resistance. Our result shows that similarity in codon usage pattern is
      an important factor to be taken into account when exogenous transgenes are
      expressed in Frankia cells.

PMID- 24287651
TI  - What stories can the Frankia genomes start to tell us?
AB  - Among the Actinobacteria, the genus Frankia is well known for its facultative
      lifestyle as a plant symbiont of dicotyledonous plants and as a free-living soil
      dweller. Frankia sp. strains are generally classified into one of four major
      phylogenetic groups that have distinctive plant host ranges. Our understanding of
      these bacteria has been greatly facilitated by the availability of the first
      three complete genome sequences, which suggested a correlation between genome
      size and plant host range. Since that first report, eight more Frankia genomes
      have been sequenced. Representatives from all four lineages have been sequenced
      to provide vital baseline information for genomic approaches toward understanding
      these novel bacteria. An overview of the Frankia genomes will be presented to
      stimulate discussion on the potential of these organisms and a greater
      understanding of their physiology and evolution.

PMID- 24287652
TI  - Characterization of pseudogenes in members of the order Frankineae.
AB  - Pseudogenes are defined as non-functional relatives of genes whose protein-coding
      abilities are lost and are no longer expressed within cells. They are an outcome
      of accumulation of mutations within a gene whose end product is not essential for
      survival. Proper investigation of the procedure of pseudogenization is relevant
      for estimating occurrence of duplications in genomes. Frankineae houses an
      interesting group of microorganisms, carving a niche in the microbial world. This
      study was undertaken with the objective of determining the abundance of
      pseudogenes, understanding strength of purifying selection, investigating
      evidence of pseudogene expression, and analysing their molecular nature, their
      origin, evolution and deterioration patterns amongst domain families.
      Investigation revealed the occurrence of 956 core pFAM families sharing common
      characteristics indicating co-evolution. WD40, Rve_3, DDE_Tnp_IS240 and phage
      integrase core domains are larger families, having more pseudogenes, signifying a
      probability of harmful foreign genes being disabled within transposable elements.
      High selective pressure depicted that gene families rapidly duplicating and
      evolving undoubtedly facilitated creation of a number of pseudogenes in
      Frankineae. Codon usage analysis between protein-coding genes and pseudogenes
      indicated a wide degree of variation with respect to different factors. Moreover,
      the majority of pseudogenes were under the effect of purifying selection.
      Frankineae pseudogenes were under stronger selective constraints, indicating that
      they were functional for a very long time and became pseudogenes abruptly. The
      origin and deterioration of pseudogenes has been attributed to selection and
      mutational pressure acting upon sequences for adapting to stressed soil
      environments.

PMID- 24287653
TI  - Functional divergence outlines the evolution of novel protein function in
      NifH/BchL protein family.
AB  - Biological nitrogen fixation is accomplished by prokaryotes through the catalytic
      action of complex metalloenzyme, nitrogenase. Nitrogenase is a two-protein
      component system comprising MoFe protein (NifD and K) and Fe protein (NifH). NifH
      shares structural and mechanistic similarities as well as evolutionary
      relationships with light-independent protochlorophyllide reductase (BchL), a
      photosynthesis-related metalloenzyme belonging to the same protein family. We
      performed a comprehensive bioinformatics analysis of the NifH/BchL family in
      order to elucidate the intrinsic functional diversity and the underlying
      evolutionary mechanism among the members. To analyse functional divergence in the
      NifH/ BchL family, we have conducted pair-wise estimation in altered evolutionary
      rates between the member proteins. We identified a number of vital amino acid
      sites which contribute to predicted functional diversity. We have also made use
      of the maximum likelihood tests for detection of positive selection at the amino
      acid level followed by the structure-based phylogenetic approach to draw
      conclusion on the ancient lineage and novel characterization of the NifH/BchL
      protein family. Our investigation provides ample support to the fact that NifH
      protein and BchL share robust structural similarities and have probably deviated
      from a common ancestor followed by divergence in functional properties possibly
      due to gene duplication.

PMID- 24287654
TI  - Growth response of Casuarina equisetifolia Forst. rooted stem cuttings to Frankia
      in nursery and field conditions.
AB  - Casuarina equisetifolia Forst. is a tree crop that provides fuel wood, land
      reclamation, dune stabilization, and scaffolding for construction, shelter belts,
      and pulp and paper production. C. equisetifolia fixes atmospheric nitrogen
      through a symbiotic relationship with Frankia, a soil bacterium of the
      actinobacteria group. The roots of C. equisetifolia produce root nodules where
      the bacteria fix atmospheric nitrogen, which is an essential nutrient for all
      plant metabolic activities. However, rooted stem cuttings of elite clones of C.
      equisetifolia by vegetative propagation is being planted by the farmers of
      Pondicherry as costeffective method. As the vegetative propagation method uses
      inert material (vermiculite) for rooting there is no chance for Frankia
      association. Therefore after planting of these stocks the farmers are applying
      150 kg of di-ammonium phosphate (DAP)/acre/year. To overcome this fertilizer
      usage, the Frankia-inoculated rooted stem cuttings were propagated under nursery
      conditions and transplanted in the nutrient-deficient soils of Karaikal,
      Pondicherry (India), in this study. Under nursery experiments the growth and
      biomass of C. equisetifolia rooted stem cuttings inoculated with Frankia showed 3
      times higher growth and biomass than uninoculated control. These stocks were
      transplanted and monitored for their growth and survival for 1 year in the
      nutrient-deficient farm land. The results showed that the rooted stem cuttings of
      C. equisetifolia significantly improved growth in height (8.8 m), stem girth (9.6
      cm) and tissue nitrogen content (3.3 mg g-1) than uninoculated controls. The soil
      nutrient status was also improved due to inoculation of Frankia.

PMID- 24287655
TI  - Indigenous actinorhizal plants of Australia.
AB  - Indigenous species of actinorhizal plants of Casuarinaceae, Elaeagnaceae and
      Rhamnaceae are found in specific regions of Australia. Most of these plants
      belong to Casuarinaceae, the dominant actinorhizal family in Australia. Many of
      them have significant environmental and economical value. The other two families
      with their indigenous actinorhizal plants have only a minor presence in
      Australia. Most Australian actinorhizal plants have their native range only in
      Australia, whereas two of these plants are also found indigenously elsewhere. The
      nitrogen-fixing ability of these plants varies between species. This ability
      needs to be investigated in some of these plants. Casuarinas form a distinctive
      but declining part of the Australian landscape. Their potential has rarely been
      applied in forestry in Australia despite their well-known uses, which are being
      judiciously exploited elsewhere. To remedy this oversight, a programme has been
      proposed for increasing and improving casuarinas that would aid in greening more
      regions of Australia, increasing the soil fertility and the area of wild life
      habitat (including endangered species). Whether these improved clones would be
      productive with local strains of Frankia or they need an external inoculum of
      Frankia should be determined and the influence of mycorrhizal fungi on these
      clones also should be investigated.

PMID- 24287656
TI  - Growth and N2 fixation in an Alnus hirsuta (Turcz.) var. sibirica stand in Japan.
AB  - To estimate the N2 fixation ability of the alder (Alnus hirsuta (Turcz.) var.
      sibirica), we examined the seasonal variation in nitrogenase activity of nodules
      using the acetylene reduction method in an 18-year-old stand naturally
      regenerated after disturbance by road construction in Japan. To evaluate the
      contribution of N2 fixation to the nitrogen (N) economy in this alder stand, we
      also measured the phenology of the alder, the litterfall, the decomposition rate
      of the leaf litter, and N accumulation in the soil. The acetylene reduction
      activity per unit nodule mass (ARA) under field conditions appeared after bud
      break, peaked the maximum in midsummer after full expansion of the leaves, and
      disappeared after all leaves had fallen. There was no consistent correlation
      between ARA and tree size (dbh). The amount of N2 fixed in this alder stand was
      estimated at 56.4 kg ha-1 year-1 when a theoretical molar ratio of 3 was used to
      convert the amount of reduced acetylene to the amount of fixed N2. This amount of
      N2 fixation corresponded to the 66.4 percent of N in the leaf litter produced in
      a year. These results suggested that N2 fixation still contributed to the large
      portion of N economy in this alder stand.

PMID- 24287657
TI  - Characterization of haemoglobin from actinorhizal plants--an in silico approach.
AB  - Plant haemoglobins (Hbs), found in both symbiotic and non-symbiotic plants, are
      heme proteins and members of the globin superfamily. Hb genes of actinorhizal
      Fagales mostly belong to the non-symbiotic type of haemoglobin; however, along
      with the non-symbiotic Hb, Casuarina sp. posses a symbiotic one (symCgHb), which
      is expressed specifically in infected cells of nodules. A thorough sequence
      analysis of 26 plant Hb proteins, currently available in public domain, revealed
      a consensus motif of 29 amino acids. This motif is present in all the members of
      symbiotic class II Hbs including symCgHb and non-symbiotic Class II Hbs, but is
      totally absent in Class I symbiotic and non-symbiotic Hbs. Further, we
      constructed 3D structures of Hb proteins from Alnus and Casuarina through
      homology modelling and peeped into their structural properties. Structure-based
      studies revealed that the Casuarina symbiotic haemoglobin protein shows distinct
      stereochemical properties from that of the other Casuarina and Alnus Hb proteins.
      It also showed considerable structural similarities with leghemoglobin structure
      from yellow lupin (pdb id 1GDI). Therefore, sequence and structure analyses point
      to the fact that symCgHb protein shows significant resemblance to symbiotic
      haemoglobin found in legumes and may thus eventually play a similar role in
      shielding the nitrogenase from oxygen as seen in the case of leghemoglobin.

PMID- 24287658
TI  - Amplicon restriction patterns associated with nitrogenase activity of root
      nodules for selection of superior Myrica seedlings.
AB  - Trees of Myrica sp. grow abundantly in the forests of Meghalaya, India. These
      trees are actinorhizal and harbour nitrogen-fixing Frankia in their root nodules
      and contribute positively towards the enhancement of nitrogen status of forest
      areas. They can be used in rejuvenation of mine spoils and nitrogen-depleted
      fallow lands generated due to slash and burn agriculture practiced in the area.
      We have studied the association of amplicon restriction patterns (ARPs) of Myrica
      ribosomal RNA gene and internal transcribed spacer (ITS) region and nitrogenase
      activity of its root nodules. We found that ARPs thus obtained could be used as
      markers for early screening of seedlings that could support strains of Frankia
      that fix atmospheric nitrogen more efficiently.

PMID- 24287659
TI  - Evaluation of phytochemical constituents and antioxidant activity of selected
      actinorhizal fruits growing in the forests of Northeast India.
AB  - Hippophae salicifolia, Elaeagnus pyriformis, Myrica esculenta and M. nagi are
      actinorhizal plants growing in the sacred forests of Northeast India with
      multipurpose uses. The present investigation was undertaken to determine the
      phenol, flavonoid and flavonol contents of the fresh fruit juice of these plant
      species including the antioxidant potential by means of DPPH, H2O2 and NO
      scavenging activity and FRP. The total phenolic, flavonoid and flavonol contents
      of fruit juice ranged from 321.68+/-0.06 to 76.67+/-0.01 mg/g GAE, 272.92+/-0.07
      to 20.12+/-0.02 mg/g QE and 258.92+/-0.08 to 18.72+/-0.02 mg/g QE, respectively.
      At 2.0 mg/mL concentration, DPPH scavenging activity was found to be the highest
      in M. esculenta (89.62 percent) and the lowest in E. pyriformis (17.58 percent).
      The reducing power activity was found significantly higher in H. salicifolia
      juice, which increased with increase in concentration. The H2O2 scavenging
      activity of H. salicifolia juice was found to be as high as 98.78 percent, while
      Elaeagnus juice was found to be less effective with just 48.90 percent. Juice of
      H. salicifolia showed the greatest NO scavenging effect of 75.24 percent as
      compared to juice of E. pyriformis, where only 37.54 percent scavenging was
      observed at the same concentration. Taking into account all the experimental
      data, it can be said that the fruits of H. salicifolia and both M. nagi and M.
      esculenta have good antioxidant activity compared to fruits of E. pyriformis.

PMID- 24287660
TI  - In silico-based combinatorial pharmacophore modelling and docking studies of GSK
      3beta and GK inhibitors of Hippophae.
AB  - Type 2 diabetes is an inevitably progressive disease, with irreversible beta cell
      failure. Glycogen synthase kinase and Glukokinase, two important enzymes with
      diverse biological actions in carbohydrate metabolism, are promising targets for
      developing novel antidiabetic drugs. A combinatorial structure-based molecular
      docking and pharmacophore modelling study was performed with the compounds of
      Hippophae salicifolia and H. rhamnoides as inhibitors. Docking with Discovery
      Studio 3.5 revealed that two compounds from H. salicifolia, viz Lutein D and an
      analogue of Zeaxanthin, and two compounds from H. rhamnoides, viz Isorhamnetin-3
      rhamnoside and Isorhamnetin-7-glucoside, bind significantly to the GSK-3 beta
      receptor and play a role in its inhibition; whereas in the case of Glucokinase,
      only one compound from both the plants, i.e. vitamin C, had good binding
      characteristics capable of activation. The results help to understand the type of
      interactions that occur between the ligands and the receptors. Toxicity
      predictions revealed that none of the compounds had hepatotoxic effects and had
      good absorption as well as solubility characteristics. The compounds did not
      possess plasma protein-binding, crossing blood-brain barrier ability. Further, in
      vivo and in vitro studies need to be performed to prove that these compounds can
      be used effectively as antidiabetic drugs.

PMID- 24287661
TI  - Casuarina glauca: a model tree for basic research in actinorhizal symbiosis.
AB  - Casuarina glauca is a fast-growing multipurpose tree belonging to the
      Casuarinaceae family and native to Australia. It requires limited use of chemical
      fertilizers due to the symbiotic association with the nitrogen-fixing
      actinomycete Frankia and with mycorrhizal fungi, which help improve phosphorous
      and water uptake by the root system. C. glauca can grow in difficult sites,
      colonize eroded lands and improve their fertility, thereby enabling the
      subsequent growth of more demanding plant species. As a result, this tree is
      increasingly used for reforestation and reclamation of degraded lands in tropical
      and subtropical areas such as China and Egypt. Many tools have been developed in
      recent years to explore the molecular basis of the interaction between Frankia
      and C. glauca. These tools include in vitro culture of the host and genetic
      transformation with Agrobacterium, genome sequencing of Frankia and related
      studies, isolation of plant symbiotic genes combined with functional analyses
      (including knock-down expression based on RNA interference), and transcriptome
      analyses of roots inoculated with Frankia or Rhizophagus irregularis. These
      efforts have been fruitful since recent results established that many common
      molecular mechanisms regulate the nodulation process in actinorhizal plants and
      legumes, thus providing new insights into the evolution of nitrogen-fixing
      symbioses.

PMID- 24287662
TI  - Interventions aimed at improving performance on medication adherence metrics.
AB  - BACKGROUND: medication adherence is one determining factor of treatment success.
      Poor medication adherence mitigates optimum clinical benefits and increases total
      health care costs. Current evidence suggests that for population-based adherence
      interventions to be effective, a multidisciplinary, multifactorial approach that
      can be tailored for each individual should be adopted. In the United States,
      national organizations such as the National Committee for Quality Assurance and
      the Centers for Medicare and Medicaid Services include medication adherence as a
      metric of health care system performance Aim of the COMMENTARY: This article
      provides an overview of efforts at Kaiser Permanente Colorado to impact
      medication adherence-related metrics. Described interventions are supported by
      electronic data gathering processes with an emphasis on the role of pharmacists.

PMID- 24287664
TI  - Erratum to: how do surgeons approach breast cancer surgery in Turkey? A national
      survey.

PMID- 24287663
TI  - Weaning from intravenous prostanoids and normalization of hemodynamics by long
      term imatinib therapy in severe idiopathic pulmonary arterial hypertension.
AB  - INTRODUCTION: Despite new treatment options targeted at its three main pathogenic
      pathways, prognosis of idiopathic pulmonary arterial hypertension has remained
      dismal, with 3-year survival rates around 70 %. Antiproliferative agents have
      emerged as a new therapeutic concept. However, they may exert their effects only
      after a prolonged period of time. CASE DESCRIPTION: Herein we present a patient
      who, despite being on a triple targeted drug therapy including high-dose
      intravenous prostanoids, still had severe pulmonary hypertension. After 4 years
      treatment with the tyrosine kinase inhibitor imatinib, the patient could be
      weaned from intravenous prostanoids and attained a persistent hemodynamic
      normalization. CONCLUSIONS: Antiproliferative agents might be a promising new
      class of drugs in pulmonary arterial hypertension. However, the occurrence of
      unexpected side effects like the increased incidence of subdural hematomas, has
      led to the recommendation that at present such an off-label use is strongly
      discouraged, and that further studies elucidating the risk/benefit ratio of
      tyrosine kinase inhibitors are clearly needed.

PMID- 24287665
TI  - Square planar platinum(II) complexes with N,S-donor ligands: synthesis,
      characterisation, DNA interaction and cytotoxic activity.
AB  - The platinum(II) complexes with N,S-donor ligand have been synthesised and
      characterised by physiological techniques like elemental, electronic, Fourier
      transform infrared, hydrogen-1 nuclear magnetic resonance ((1)H NMR) and liquid
      chromatography-mass spectrometry spectra. The synthesised complexes have been
      checked for their DNA binding ability by absorption titration and viscosity
      measurement, and the results show that the complexes binds to herring sperm DNA
      (HS DNA) via covalent mode of binding. The DNA cleavage activity of synthesised
      complexes has been carried out by gel electrophoresis experiment using
      supercoiled form of pUC19 DNA, showing the unwinding of the negatively charged
      supercoiled DNA. Brine shrimp (Artemia cysts) lethality bioassay technique has
      been applied for the determination of toxic property of synthesised complexes in
      terms of micromolars. 

PMID- 24287666
TI  - A highly selective, Hg2+ triggered hydrogelation: modulation of morphology by
      chemical stimuli.
AB  - We report the first Hg(2+) selective hydrogelation by 4'-[4-(4
      aminophenyl)phenyl]-2,2':6',2''-terpyridine. The gel showed remarkable response
      towards specific chemical agents such as benzo-18-crown-6 ether and K(+) which
      enabled extensive modulation of the gel morphology. 

PMID- 24287667
TI  - Highly magnetic iron carbide nanoparticles as effective T(2) contrast agents.
AB  - This paper reports that iron carbide nanoparticles with high air-stability and
      strong saturation magnetization can serve as effective T2 contrast agents for
      magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit
      strong contrast enhancement with an r2 value of 283.2 mM(-1) S(-1), which is
      about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM(-1) S(
      1)). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce
      much more significant MRI contrast enhancement than conventional Fe3O4
      nanoparticles in living subjects, which holds great promise in biomedical
      applications.

PMID- 24287668
TI  - Electronic tuning of nitric oxide release from manganese nitrosyl complexes by
      visible light irradiation: enhancement of nitric oxide release efficiency by the
      nitro-substituted quinoline ligand.
AB  - Manganese nitrosyl {MnNO}(6) complexes of general formula [Mn(dpaq(R))(NO)]ClO4
      (1R), where dpaq(R) denotes a series of pentadentate monoamido ligands, 2-[N,N
      bis(pyridin-2-ylmethyl)]-amino-N'-quinolin-8-yl-acetamido with R = OMe, H, Cl and
      NO2 at the 5-position of the quinoline moiety, were prepared. The derivatives 1R
      were characterized by (1)H NMR, IR and UV-vis spectrometry as well as by single
      crystal X-ray crystallography. The N-O bond and the amido C=O bond stretching
      frequencies, as well as the redox potentials of 1R derivatives, substantially
      varied depending on the nature of the substituent group R on the quinoline ring,
      indicating that the pi back-bonding from Mn to NO groups becomes weak as the
      substituent group R becomes more electron withdrawing. The nitro-substituted
      derivative 1NO2 is unique among the series; the tail of its absorption bands
      extends to the NIR region (up to 700 nm), and the apparent NO releasing rate from
      1NO2 by light irradiation at 650 nm was ca. 4-fold higher than the other
      derivatives.

PMID- 24287669
TI  - Spread of epidemic Clostridium difficile NAP1/027 in Latin America: case reports
      in Panama.
AB  - The rate and severity of Clostridium difficile infection (CDI) have been linked
      to the emergence and spread of the hypervirulent toxigenic strain NAP1/027. This
      strain has been responsible for large outbreaks in healthcare facilities in North
      America and Europe and most recently in Latin America. This is the first report
      of the NAP1 strain in Panama. It suggests that the spread of C. difficile NAP1
      throughout Latin America could be a possibility as evidenced in the following
      case reports. Five isolates typed as NAP1 had tcdA, tcdB, binary toxin gene cdtB
      and tcdC deletion. All isolates were resistant to clindamycin, fluoroquinolones
      and rifampicin. Under this scenario, surveillance programmes for CDI should be
      implemented in public health facilities in Latin America and diagnosis of CDI
      should be considered, especially in patients with predisposing factors. 

PMID- 24287670
TI  - Association between intra-abdominal pressure and jugular bulb saturation in
      critically ill patients.
AB  - BACKGROUND: Disorders in cerebral circulation following elevated intra-abdominal
      pressure (IAP) may lead to silent brain ischemia, which can be serious problem in
      sedated critically ill patients. The aim of the present study was to analyse the
      possible association between jugular venous bulb pressure (JVBP) and jugular
      venous bulb saturation (SjO2) to IAP in critically ill patients. METHODS: Adult
      septic shock patients with acute kidney injury were studied just after the
      admission to Intensive Care Unit and after 24 and 48 hours of treatment. Patients
      were divided into: CVVH group (patients treated with continuous veno-venous
      haemofiltration) and furosemide group (patients treated with furosemide
      infusion). The IAP was measured via the bladder. The right jugular vein was
      retrogradely cannulated for JVBP and SjO2 measurement. Intra-abdominal
      hypertension was defined as a sustained increase of IAP equal to or above 12
      mmHg. RESULTS: Forty patients (25 male and 15 female patients) were studied. In
      all participants, IAP strongly correlated with JVBP (P<0.001, r=0.73). This
      correlation was stronger in the furosemide group than the CVVH group. Moreover,
      an increase in IAP was related to an increase in JVBP and a decrease in SjO2.
      There was an inverse correlation between IAP and SjO2 (P<0.001, r=-0.55). This
      correlation was stronger in furosemide group than CVVH group. CONCLUSION: IAP is
      correlated to JVBP and inversely correlated to SjO2. Increase in IAP leads to
      elevation in JVBP and decrease in SjO2. Renal replacement therapy disturbs the
      correlation between IAP, JVBP and SjO2.

PMID- 24287671
TI  - A systematic review of antifibrinolytics and massive injury.
AB  - Every year, more than a million people die as a result of trauma. This huge
      mortality could be partially explained by the development of an acute traumatic
      coagulopathy, present in a large part of all major trauma patients, soon after
      injury, which contributes to ongoing hemorrhage. The coagulopathy induced by
      trauma is independently associated with mortality, increased transfusion
      requirements, multiple organ dysfunction, infections, increased intensive care
      unit (ICU) length of stay, and costs. The pathophysiological mechanisms
      implicated in this acute traumatic coagulopathy are complexes and lead to
      generate a vicious circle leading to the activation of different pathways:
      thrombin generation, plasmin generation, inflammation activation. All of these
      processes will impair the balance between clot formation and clot lysis, with an
      increased tendency of hyperfibrinolysis. In 2010, the CRASH-2 trial demonstrated
      that tranexamic acid (TXA) administration was associated with a reduction in all
      cause mortality (14.5% vs. 16%, P=0.0035), including the risk of death due to
      bleeding (4.9% vs. 5.8%, P=0.0077), without an increase in fatal or non-fatal
      vascular occlusive events. Finally, the CRASH-3 trial is now recruiting patients
      with traumatic brain injury without extracranial bleeding. This study aims at
      determining the safety and efficacy of TXA administration in this particular
      setting. Our experience from the cardiac surgery setting highlighted a dose
      dependent increased seizure incidence associated with the administration of TXA.
      For this reason, further studies are needed to better define the "optimal" dose
      scheme based on pharmacokinetic and pharmacodynamic studies. 

PMID- 24287672
TI  - Propofol versus thiopental use in patients undergoing craniotomy.

PMID- 24287673
TI  - Advances in weaning patients from mechanical ventilation: could near-infrared
      spectroscopy help?

PMID- 24287674
TI  - Recompression in new levels after percutaneous vertebroplasty and kyphoplasty
      compared with conservative treatment.
AB  - STUDY DESIGN: A prospective clinical study assessing new vertebral compression
      fracture after previous treatment. OBJECTIVE: The purpose of this study was to
      investigate the incidence and associated risk factors of new symptomatic
      osteoporotic vertebral compression fractures (OVCFs) in patients treated by
      percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) versus conservative
      treatment, and to elucidate our findings. There are a lot of reports concerning
      the feasibility and efficacy of this minimally invasive procedure compared with
      conservative treatment, especially in pain soothing. However, it is still unclear
      whether the risk of subsequent fracture has increased among operative treatment
      patients in the long term. METHODS: From November 2005 to July 2009, 290
      consecutive patients with 363 OVCFs were randomly selected for PVP/PKP or
      conservative treatment and evaluated with a mean follow-up of 49.4 months (36-80
      months). Some parameters were characterized and statistically compared in this
      study. Telephone questionnaires, clinical reexamine, and plain radiographs were
      performed in the follow-up. RESULTS: Thirty-one of 290 (10.7%) patients had
      experienced 42 newly developed symptomatic secondary OVCFs. Among 169 operation
      (53.3% vertebroplasty, 46.7% kyphoplasty) and 121 comparison patients, there is
      no significant statistical difference of new OVCFs incidence between the two
      groups calculated by patient proportion. However, in separate, the rate of
      secondary adjacent fractures calculated by vertebral refracture number is
      significantly higher than non-adjacent levels in PVP/PKP group but no significant
      statistical difference was observed in conservative group. The time interval of
      recompression after operative procedure was much shorter than that for comparison
      group (9.7 +/- 17.8 versus 22.4 +/- 7.99 months, p = 0.017). In addition, older
      age, gender, fracture times, location of original fracture segment, the amount of
      cement, cement leakage, operation modality (PVP or PKP),and initial number of
      OVCFs were documented, but these were not the influencing factors in this study
      (p > 0.05). CONCLUSIONS: Patients who had experienced PVP/PKP were not associated
      with an increased risk of recompression in new levels. However, recompression in
      new levels of PVP/PKP group occurred much sooner than that of conservative group
      in the follow-up period. The incidence of new vertebral fractures observed at
      adjacent levels was substantially higher but no sooner than at distant levels in
      PVP/PKP group. No major risk factors involving new OVCFs have been found in this
      study and augmentation for sandwich situation is not necessary.

PMID- 24287675
TI  - Alteration of the patellar height following total knee arthroplasty.
AB  - INTRODUCTION: Patellofemoral related complications after total knee arthroplasty
      (TKA) remain clinically relevant. The hypothesis of the present study was that
      the patellar height changes more than 10% of its preoperative height after TKA.
      Possible influences of age, gender, side and navigation system on patellar height
      were evaluated separately in subgroups. MATERIALS AND METHODS: A total of 107
      knees were enrolled after primary TKA. The patellar height was determined for
      each patient preoperatively, 1 week and 1 year postoperatively on routinely
      performed standing lateral view radiographs at 30 degrees  knee flexion. Insall
      Salvati index (ISI), modified Insall-Salvati index (MIS) as well as Miura
      Kawamura index (MKI) were determined for the whole cohort. RESULTS: One week
      after TKA the ISI, MIS and MKI changed by more than 10% in 24 (22%), 33 (30%) and
      54 (50%) cases, respectively. Moreover, the 1 year follow-up revealed a decrease
      or increase of ISI in 30 (28%), MIS in 47 (44 %) and MK in 65 (61%) knees. The
      frequency of patella alta, norma and baja preoperatively as well as 1 week and 1
      year postoperatively were not significantly different. Significant differences of
      patellar height changes were not noted between the defined subgroups.
      CONCLUSIONS: The present study demonstrates that TKA leads, at 1 week and 1 year
      follow-up, to patellar height alteration more than 10% in a significant number of
      knee joints. However, with the use of ISI and MIS the changes of patellar height
      did not exceed the defined thresholds to be classified as patella alta or baja.

PMID- 24287676
TI  - A new cathode material for super-valent battery based on aluminium ion
      intercalation and deintercalation.
AB  - Due to their small footprint and flexible siting, rechargeable batteries are
      attractive for energy storage systems. A super-valent battery based on aluminium
      ion intercalation and deintercalation is proposed in this work with VO2 as
      cathode and high-purity Al foil as anode. First-principles calculations are also
      employed to theoretically investigate the crystal structure change and the
      insertion-extraction mechanism of Al ions in the super-valent battery. Long cycle
      life, low cost and good capacity are achieved in this battery system. At the
      current density of 50 mAg(-1), the discharge capacity remains 116 mAhg(-1) after
      100 cycles. Comparing to monovalent Li-ion battery, the super-valent battery has
      the potential to deliver more charges and gain higher specific capacity.

PMID- 24287677
TI  - The true stone composition and abnormality of urinary metabolic lithogenic
      factors of rats fed diets containing melamine.
AB  - To better understand the toxicity of melamine to humans, the stone composition
      and urinary metabolic lithogenic factors of rats fed diets containing melamine
      including the infant's melamine-induced stone composition were studied. Sixty 4
      week-old male rats divided into three groups were, respectively, fed diets
      containing no melamine (control), 0.1% melamine, and 1% melamine for 4 weeks. At
      the end of experiment, the collected stones and 24-h urines from rats were,
      respectively, measured with compositions and metabolic lithogenic parameters. The
      stone from an infant who ingested melamine-adulterated formula was also included
      in compositional analysis. Across three groups, the stone was only detected in 1%
      melamine group, with composition of almost melamine different from the affected
      infant's stone composed of melamine and uric acid with a ratio of 1:2. Compared
      with control group, urine calcium and phosphate excretions were significantly
      increased in 1% melamine group. Urine uric acid excretion was significantly
      increased but citrate excretion was significantly decreased in 0.1% and 1%
      melamine groups. Urine oxalate excretion and pH were indicated without any
      significant difference. In addition based on urine physicochemical characters,
      melamine-uric acid stone seems difficult to be formed in the rats due to their
      characters of urine high-pH and low-uric acid. These results demonstrated that
      (1) the stone composition of rats fed melamine was not and could not be as that
      of infants fed melamine-adulterated formula, two species had a different
      mechanism of melamine-induced stone formation; (2) the exposure of melamine could
      result in abnormalities of urine metabolic lithogenic factors to rats, perhaps as
      well as human beings.

PMID- 24287678
TI  - Long-distance distribution of genuine energy-time entanglement.
AB  - Any practical realization of entanglement-based quantum communication must be
      intrinsically secure and able to span long distances avoiding the need of a
      straight line between the communicating parties. The violation of Bell's
      inequality offers a method for the certification of quantum links without knowing
      the inner workings of the devices. Energy-time entanglement quantum communication
      satisfies all these requirements. However, currently there is a fundamental
      obstacle with the standard configuration adopted: an intrinsic geometrical
      loophole that can be exploited to break the security of the communication, in
      addition to other loopholes. Here we show the first experimental Bell violation
      with energy-time entanglement distributed over 1 km of optical fibres that is
      free of this geometrical loophole. This is achieved by adopting a new
      experimental design, and by using an actively stabilized fibre-based long
      interferometer. Our results represent an important step towards long-distance
      secure quantum communication in optical fibres. 

PMID- 24287679
TI  - Usage tests of oak moss absolutes containing high and low levels of atranol and
      chloroatranol.
AB  - Atranol and chloroatranol are strong contact allergens in oak moss absolute, a
      lichen extract used in perfumery. Fifteen subjects with contact allergy to oak
      moss absolute underwent a repeated open application test (ROAT) using solutions
      of an untreated oak moss absolute (sample A) and an oak moss absolute with
      reduced content of atranol and chloroatranol (sample B). All subjects were in
      addition patch-tested with serial dilutions of samples A and B. Statistically
      significantly more subjects reacted to sample A than to sample B in the patch
      tests. No corresponding difference was observed in the ROAT, though there was a
      significant difference in the time required to elicit a positive reaction. Still,
      the ROAT indicates that the use of a cosmetic product containing oak moss
      absolute with reduced levels of atranol and chloroatranol is capable of eliciting
      an allergic reaction in previously sensitised individuals.

PMID- 24287680
TI  - Evaluation of post-operative complications associated with repeat resection and
      BCNU wafer implantation in recurrent glioblastoma.
AB  - BACKGROUND: Patients with glioblastoma treated with BCNU wafer implantation for
      recurrence frequently receive frontline chemoradiotherapy with temozolomide as
      part of the Stupp protocol. A retrospective investigation was conducted of
      surgical complications in a cohort of these patients treated at a single
      institution. METHODS: We searched our institutional database for patients treated
      between January 2006 and October 2012 who had recurrent glioblastoma previously
      treated with open surgery followed by the Stupp protocol and then underwent
      repeat resection with or without BCNU wafers for recurrent disease. Rates of
      select post-operative complications within 3 months of surgery were estimated.
      RESULTS: We identified 95 patients with glioblastoma who underwent resection
      followed by the Stupp protocol as frontline treatment. At disease recurrence
      (first and second recurrence), 63 patients underwent repeat resection with BCNU
      wafer implantation and 32 without implantation. Generally, BCNU wafer use was
      associated with minor to moderate increases in rates of select complications
      versus non-implantation-wound healing abnormalities (14.2 vs. 6.2 %),
      cerebrospinal fluid leak (7.9 vs. 3.1 %), hydrocephalus requiring
      ventriculoperitoneal shunt (6.3 vs. 9.3 %), chemical meningitis (3.1 vs. 0 %),
      cerebral infections (3.1 vs. 0 %), cyst formation (3.1 vs. 3.1 %), cerebral edema
      (4.7 vs. 0 %), and empyema formations (1.5 vs. 0 %). Performance status was well
      maintained post-operatively in both groups. Median progression-free survival from
      the time of first recurrence was 6.0 and 5.0 months, respectively. CONCLUSIONS:
      The use of the Stupp protocol as frontline therapy in patients with glioblastoma
      does not preclude the use of BCNU wafers at the time of progression.

PMID- 24287681
TI  - Fistula component of cerebral arteriovenous malformations: morphologic change
      after stereotactic radiosurgery and outcome of embolisation.
AB  - BACKGROUND: The angioarchitecture of arteriovenous fistulas (AVFs) of cerebral
      arteriovenous malformation (CAVM) after stereotactic radiosurgery (SRS) remain
      unclear. The purpose of this study is to report the angiographic change of AVF
      components of CAVMs after SRS and outcomes of endovascular embolisation. METHODS:
      From 2002 to 2012, a total of 523 CAVMs had been treated primarily by SRS with
      more than 3-year latency. Among these databases, there were 19 patients with 21
      AVFs undergoing embolization after SRS. We retrospectively analyzed the
      angioarchitecture of the CAVM to identify AVFs, morphologic change and outcomes
      of AVFs after SRS and embolisation. RESULTS: Eight AVFs were in the periphery of
      CAVMs, the other 13 were in a central location. Eighteen of 21 AVFs remained
      constant in morphology after SRS, while three feeders of AVFs were associated
      with radiation arteritis. The causes of failure to identify AVFs before SRS were
      overlooked (n = 7) or there was superimposition with feeders, nidus and/or venous
      drains of CAVMs (n = 14). Total fistula occlusion was achieved in all 21 AVFs;
      residual CAVMs was totally obliterated by embolisation and/or additional SRS in
      12 patients. One patient had a small procedure-related intracerebral hemorrhage.
      Mean follow-up period was 26 months. CONCLUSIONS: Early detection of AVF
      components of CAVMs prior to SRS may be difficult, particularly those in a
      central location. However, most AVFs became evident and showed consistency in
      angiographic morphology after obliteration of the majority nidus parts of CAVMs.
      Endovascular embolisation is effective in managing these AVF components.

PMID- 24287682
TI  - Relationship between the pituitary stalk angle in prefixed, normal, and postfixed
      optic chiasmata: an anatomic study with microsurgical application.
AB  - BACKGROUND: The relationship between the optic apparatus and the skull base is
      important during approaches near the sella turcica. One relationship that
      dictates which approach is taken is whether the optic chiasm is prefixed or
      postfixed or in a "normal" location, (centered over the diaphragma sella). The
      relationship between the position of the chiasm and the angulation of the
      pituitary stalk has not been investigated. METHODS: Forty adult cadavers without
      intracranial pathology were dissected and parasagitally hemisected lateral to the
      sella turcica. The angulations between the pre- and postfixed and normal chiasm
      and the pituitary stalk were evaluated under magnification. Additionally, 50 MRIs
      performed among patients evaluating headache were analyzed for these
      relationships. RESULTS: For cadavers, the chiasm was prefixed in 7.5% (n = 3),
      normal in 85% (n = 34), and postfixed in 7.5% (n = 3). On imaging, the chiasm was
      prefixed in 4% (n = 2), normal in 88% (n = 44), and postfixed in 8 % (n = 4). For
      all, the relation between the type of chiasm and the pituitary stalk was more
      often (p < 0.05) 90 degrees  or greater for prefixed chiasmata and acute angles
      for normal or postfixed chiasmata. CONCLUSIONS: These data may assist skull base
      surgeons when approaching pathology near the optic chiasm and pituitary stalk.

PMID- 24287683
TI  - Cervical extension magnetic resonance imaging in evaluating cervical spondylotic
      myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) may be caused by static and
      dynamic spinal cord compression, particularly during neck extension. Dynamic
      compression may be better evaluated with dynamic magnetic resonance (MR) images.
      We performed a retrospective study to determine the clinical indication for
      dynamic MR imaging, and conducted a survey regarding image interpretation by
      clinicians. METHOD: A total of 32 patients (M:F = 20:12, 60.1 +/- 10.7 years) who
      had undergone neutral/extension cervical MR imaging were included. The study
      population consisted of 22 patients with signs of cervical myelopathy (M group)
      and 10 patients without signs of myelopathy (NM group). The number of compression
      levels (complete obliteration of the anterior and posterior subarachnoid space)
      was assessed at each level in mid-sagittal, T2-weighted, neutral and extension MR
      images. Reproduced images from 22 patients in the M group were randomly arranged,
      and four experienced spine surgeons at four different institutes interpreted them
      to reach a clinicians' agreement. The agreements were then assessed with inter
      rater correlation coefficients (ICC). RESULTS: Analysis with extension MR images
      found an increased number of compression levels in 23/32 (72 %) of patients;
      20/22 in the M group and 3/10 in the NM group (p < 0.01, chi-squared test), as
      compared to findings of the neutral MR images. Clinical factors for increased
      compression levels in extension MR images were age (p < 0.01, 63.3 +/- 10.0 years
      vs. 51.9 +/- 8.1) and signs of myelopathy (p < 0.01, odds ratio, 23.33).
      Clinician agreement was improved with extension MR images; ICC was 0.67 with
      neutral and 0.81 with extension MR images. CONCLUSIONS: The evaluation of CSM may
      be improved with dynamic MR images. Dynamic MR scanning may be considered for
      elderly patients with signs of myelopathy, but an interpretation for asymptomatic
      spinal compression based exclusively on extension MR image should be made with
      caution.

PMID- 24287684
TI  - The relationship between nervus intermedius anatomy, ultrastructure,
      electrophysiology, and clinical function. Usefulness in cerebellopontine
      microsurgery.
AB  - BACKGROUND: Although previous studies have described the clinical features of the
      nervus intermedius (NI), no attempt has yet been made to describe the
      relationship between the ultrastructural and electrophysiological characteristics
      of the nervus intermedius and its motor competence. OBJECTIVE: In this study, we
      analyzed the intraoperative electrophysiological response obtained during
      vestibular schwannoma surgery. The ultrastructure was studied using electron
      microscopy. MATERIALS AND METHODS: Thirty-six consecutive patients underwent
      microsurgery for vestibular schwannoma with cerebellopontine angle tumors. The
      patients were extensively monitored intraoperatively. Selective stimulation of
      the nervus intermedius was attempted in all cases. The patients were then
      examined postoperatively and followed for a minimum of 1 year. Forty-three
      isolated human brainstems were analyzed to collect the ultrastructural NI data.
      RESULTS: We found a correlation between the NI motor responses in the perinasal
      and perioral regions and the ultrastructure characteristics, with few (0.5 %) but
      large myelinated motor fibers (diameters >12 MUm). Both characteristics are
      consistent with the clinical observation of transient weakness of the levator
      anguli oris muscle. These observations indicate a relationship between the
      intraoperative electrophysiological identification of the NI nervus intermedius
      and its clinical and ultrastructural characteristics. CONCLUSIONS: Identifying
      the NI in the deformed anatomy of tumors could provide a fixed landmark during
      cerebellopontine surgery and help prevent damage of the facial nerve.

PMID- 24287685
TI  - The result of S1 double screw fixation in patients not suited for L4 and/or L5
      pedicle screw insertion.
AB  - BACKGROUND: Variable methods are available for sacropelvic fixation. The
      usefulness of S1 double screw fixation for deformity surgery is established, but
      its effectiveness in cases where the L4 and/or L5 pedicle screw is not
      appropriate has not been reported. METHODS: We reviewed medical records to
      identify long-segment, lumbar spine fixation involving S1 double screws. Nine
      such patients were treated between November 2006 and November 2012 at our center:
      all patients had infectious spondylitis involving L4 and/or L5. Two patients were
      excluded due to a limited follow-up period (< 6 months). The remaining seven
      patients were enrolled. We used dynamic X-rays or three-dimensional computed
      tomography (3D-CT) to assess any change in the lumbar alignment angle and to
      evaluate bony fusion with the graft material. RESULTS: The mean observation
      period of the seven patients was 16.9 months (range: 6-25). The mean age was
      63.43 years (range: 55-73). Four patients were women. The average number of
      fusion levels was 3.5 +/- 1.1. The ideal positioning and maintenance of the S1
      double screws and bony fusion with the graft materials were confirmed using
      serial imaging. Lordosis in the lumbar region was immediately restored after
      surgery (27.0  degrees  +/- 10.4 to 35.1  degrees  +/- 10.7), and maintained with
      slight decrease (31.6  degrees  +/- 8.8) throughout the follow-up period.
      CONCLUSIONS: S1 double screws provided stability when L4 and/or L5 pedicle screw
      fixation was not possible. Our results suggest that S1 double screws are a viable
      option for sacropelvic fixation in selected patients.

PMID- 24287686
TI  - Active polar two-fluid macroscopic dynamics.
AB  - We study the dynamics of systems with a polar dynamic preferred direction.
      Examples include the pattern-forming growth of bacteria as well as shoals of
      fish, flocks of birds and migrating insects. Due to the fact that the preferred
      direction only exists dynamically, but not statically, the macroscopic variable
      of choice is the macroscopic velocity associated with the motion of the active
      units, which are typically biological in nature. We derive the macroscopic
      equations for such a system and discuss novel static, reversible and irreversible
      cross-couplings connected to a second velocity as a variable. We analyze in
      detail how the macroscopic behavior of an active system with a polar dynamic
      preferred direction compares to other systems with two velocities including
      immiscible liquids and electrically neutral quantum liquids such as superfluid
      (4)He and (3)He . We critically discuss changes in the normal mode spectrum when
      comparing uncharged superfluids, immiscible liquids and active system with a
      polar dynamic preferred direction. We investigate the influence of a macroscopic
      hand (collective effects of chirality) on the macroscopic behavior of such active
      media. 

PMID- 24287687
TI  - Order and frustration in liquid-crystalline dendrimers.
AB  - X-ray diffraction has been used to elucidate the structure and phase behavior of
      several liquid-crystalline dendrimers with a different surface topology of the
      terminal chains. This includes second-generation liquid-crystalline block and
      statistical dendrimers with mixed aliphatic and mesogenic terminal groups as well
      as homo-dendrimers of several generations containing only mesogenic end groups.
      The homo-dendrimers of generation one to four display a monolayer smectic phase,
      while the fifth generation shows a more ordered columnar phase. The block
      dendrimer of the second generation has a bilayer smectic phase. The precise
      structure of the lamellar ordering has been determined by X-ray reflectivity from
      thin films on a substrate. The second-generation statistical dendrimer does not
      show any mesogenic phase. The observed phase behavior is discussed in terms of
      the frustration due to competition between the stiff geometry of the dendritic
      matrix and the close-packing conditions of the terminal chains. 

PMID- 24287688
TI  - Azacalix[2]arene[2]triazine-based receptors bearing carboxymethyl pendant arms on
      nitrogen bridges: synthesis and evaluation of their coordination ability towards
      copper(II).
AB  - For functional nitrogen-bridged calix(hetero)aromatic platforms to be further
      used in the design of more sophisticated receptors, the
      azacalix[2]arene[2]triazine nitrogen bridges were functionalised with methyl
      bromoacetate. Three new macrocycles with four N-methyl ester pendant arms were
      straightforwardly prepared in good yields from the undecorated
      azacalix[2]arene[2]triazine precursors with chlorine, dimethylamine or
      dihexylamine substituted triazines. These intermediate macrocycles exhibited
      different reactivity towards the nucleophilic replacement, which was rationalized
      from the computed electrostatic potential for these molecules. Subsequently, the
      N-methyl ester appendages were hydrolyzed with each dialkylamine derivative
      providing a single macrocycle with four carboxylic groups. In contrast, the
      hydrolysis of the dichlorinated azacalix[2]arene[2]triazine analogue yielded a
      mixture of three isomeric macrocycles having two N-methyl esters and two
      carboxylmethyl pendant arms and the triazine chlorine atoms replaced by hydroxyl
      groups. The coordination ability of two macrocycles with four carboxylic groups
      for transition metals was evaluated with copper(ii) by UV-vis titrations. 

PMID- 24287689
TI  - Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5
      year extension of phase III Trial.
AB  - PURPOSE: A recent phase III randomized controlled trial (NCT00434148) showed
      efficacy of pasireotide in the treatment of patients with Cushing's disease (CD).
      Patients were invited to participate in an extension phase of the protocol and a
      subgroup had a sustained response. We report the experience with 4 patients in
      our center of which 2 full responders have completed 5.5 and 4.25 years of
      treatment with disease control. METHODS: The trial protocol was described
      previously. The extension phase consisted of 3-monthly visits with clinical,
      biochemical, and imaging evaluation and investigator-driven pasireotide
      titration. Research charts were retrospectively analyzed. RESULTS: Four patients
      with persistent CD following pituitary surgery completed the first 6 months of
      the trial and 3 continued in the next 6 month open-label phase. Two patients with
      baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had
      a rapid sustained response to pasireotide and entered the extension phase after
      12 months. They remain in clinical and biochemical disease remission and 1
      patient now only requires 300 MUg daily of pasireotide. All 4 patients developed
      glucose intolerance; however, the two patients in the extension phase were
      eventually able to discontinue all diabetes pharmacotherapy. Adverse events
      included second degree atrioventicular block type 1 without QT prolongation in a
      patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis
      requiring cholecystectomy in a second patient. CONCLUSIONS: Pasireotide therapy
      can provide normalization of UFC and of clinical symptoms and signs of CD during
      up to 5 years of follow-up. This study demonstrates the possible recuperation of
      normoglycemia after continued use of pasireotide and control of underlying
      hypercortisolemia. Longer-term monitoring for potential adverse events related to
      continued use of pasireotide is indicated.

PMID- 24287691
TI  - Lead in New York City community garden chicken eggs: influential factors and
      health implications.
AB  - Raising chickens for eggs in urban areas is becoming increasingly common. Urban
      chickens may be exposed to lead, a common urban soil contaminant. We measured
      lead concentrations in chicken eggs from New York City (NYC) community gardens
      and collected information on factors that might affect those concentrations. Lead
      was detected between 10 and 167 MUg/kg in 48 % of NYC eggs. Measures of lead in
      eggs from a henhouse were significantly associated (p < 0.005) with lead
      concentrations in soil. The association between soil and egg lead has been
      evaluated only once before, by a study of a rural region in Belgium. In our
      study, the apparent lead soil-to-egg transfer efficiency was considerably lower
      than that found in Belgium, suggesting that there may be important geographic
      differences in this transfer. We developed models that suggested that, for sites
      like ours, lead concentrations in >50 % of eggs from a henhouse would exceed
      store-bought egg concentrations (<7-13 MUg/kg; 3 % above detection limit) at soil
      lead concentrations >120 mg/kg and that the concentration in one of six eggs from
      a henhouse would exceed a 100 MUg/kg guidance value at soil lead concentrations
      >410 mg/kg. Our models also suggested that the availability of dietary calcium
      supplements was another influential factor that reduced egg lead concentrations.
      Estimates of health risk from consuming eggs with the lead concentrations we
      measured generally were not significant. However, soil lead concentrations in
      this study were <600 mg/kg, and considerably higher concentrations are not
      uncommon. Efforts to reduce lead transfer to chicken eggs and associated exposure
      are recommended for urban chicken keepers.

PMID- 24287692
TI  - Strong coupling in the sub-wavelength limit using metamaterial nanocavities.
AB  - The interaction between cavity modes and optical transitions leads to new coupled
      light-matter states in which the energy is periodically exchanged between the
      matter states and the optical mode. Here we present experimental evidence of
      optical strong coupling between modes of individual sub-wavelength metamaterial
      nanocavities and engineered optical transitions in semiconductor
      heterostructures. We show that this behaviour is generic by extending the results
      from the mid-infrared (~10 MUm) to the near-infrared (~1.5 MUm). Using mid
      infrared structures, we demonstrate that the light-matter coupling occurs at the
      single resonator level and with extremely small interaction volumes. We calculate
      a mode volume of 4.9 * 10(-4) (lambda/n)(3) from which we infer that only ~2,400
      electrons per resonator participate in this energy exchange process. 

PMID- 24287690
TI  - The dipeptidyl peptidase (DPP)-4 inhibitors for type 2 diabetes mellitus in
      challenging patient groups.
AB  - Treating hyperglycemia is a critical aspect of managing type 2 diabetes mellitus
      (T2DM), but can be especially challenging in patients from vulnerable groups such
      as those with chronic kidney disease, African Americans, and older people. The
      dipeptidyl peptidase (DPP)-4 inhibitors are relatively new oral antidiabetes
      drugs that have been incorporated into treatment algorithms over the past few
      years and have also been studied in these vulnerable patients. Clinical trials
      with DPP-4 inhibitors have now been reported for all these patient groups and
      have demonstrated significant improvements in measures of hyperglycemia, with a
      good safety profile. Based on the current evidence, it appears that the DPP-4
      inhibitors are worthy of consideration not only for the most straightforward
      patients with T2DM, but also for these vulnerable patients. 

PMID- 24287693
TI  - Bioavailability of the anti-clostridial bacteriocin thuricin CD in
      gastrointestinal tract.
AB  - Thuricin CD is a two component narrow spectrum bacteriocin comprising two
      peptides with targeted activity against Clostridium difficile. This study
      examined the bioavailability of thuricin with a view to developing it as an
      effective antimicrobial against intestinal infection. One of the peptides, Trn
      beta, was found to be degraded by the gastric enzymes pepsin and alpha
      chymotrypsin both in vitro and in vivo, whereas Trn-alpha was resistant to
      digestion by these enzymes and hence was detected in the intestinal porcine
      digesta following oral ingestion by pigs. In order to determine if spores of the
      producing organism Bacillus thuringiensis DPC 6431 could be used to deliver the
      bacteriocin to the gut, spores were fed to 30 mice (approx. 10(8)-2*10(8) per
      animal) and their germination, growth and production of thuricin in the
      gastrointestinal tract (GIT) of the animals was monitored. Almost 99 % of the
      spores delivered to the GIT were excreted in the first 24 h and neither Trn-alpha
      nor Trn-beta was detected in the gut or faecal samples of the test mice,
      indicating that ingestion of B. thuringiensis spores may not be a suitable
      vehicle for the delivery of thuricin CD. When thuricin CD was delivered rectally
      to mice (n = 40) and C. difficile shedding monitored at 1, 6, 12 and 24 h post
      treatment, there was a >95 % (>1.5 log units) reduction of C. difficile 027 in
      the colon contents of infected mice (n = 10) 1 h post-treatment compared with the
      control group (n = 10; P<0.001). Furthermore, 6 h post-treatment there was a
      further 1.5 log reduction in C. difficile numbers (n = 10) relative to the
      control group (n = 10; P<0.05). These results would suggest that rectal
      administration of thuricin may be a promising mode of delivery of thuricin CD to
      the colon. 

PMID- 24287694
TI  - Choline kinase inhibition induces exacerbated endoplasmic reticulum stress and
      triggers apoptosis via CHOP in cancer cells.
AB  - Endoplasmic reticulum (ER) is a central organelle in eukaryotic cells that
      regulates protein synthesis and maturation. Perturbation of ER functions leads to
      ER stress, which has been previously associated with a broad variety of diseases.
      ER stress is generally regarded as compensatory, but prolonged ER stress has been
      involved in apoptosis induced by several cytotoxic agents. Choline kinase alpha
      (ChoKalpha), the first enzyme in the Kennedy pathway, is responsible for the
      generation of phosphorylcholine (PCho) that ultimately renders
      phosphatidylcholine. ChoKalpha overexpression and high PCho levels have been
      detected in several cancer types. Inhibition of ChoKalpha has demonstrated
      antiproliferative and antitumor properties; however, the mechanisms underlying
      these activities remain poorly understood. Here, we demonstrate that ChoKalpha
      inhibitors (ChoKIs), MN58b and RSM932A, induce cell death in cancer cells (T47D,
      MCF7, MDA-MB231, SW620 and H460), through the prolonged activation of ER stress
      response. Evidence of ChoKIs-induced ER stress includes enhanced production of
      glucose-regulated protein, 78 kDa (GRP78), protein disulfide isomerase,
      IRE1alpha, CHOP, CCAAT/enhancer-binding protein beta (C/EBPbeta) and TRB3.
      Although partial reduction of ChoKalpha levels by small interfering RNA was not
      sufficient to increase the production of ER stress proteins, silencing of
      ChoKalpha levels also show a decrease in CHOP overproduction induced by ChoKIs,
      which suggests that ER stress induction is due to a change in ChoKalpha protein
      folding after binding to ChoKIs. Silencing of CHOP expression leads to a
      reduction in C/EBPbeta, ATF3 and GRP78 protein levels and abrogates apoptosis in
      tumor cells after treatment with ChoKIs, suggesting that CHOP maintains ER stress
      responses and triggers the pro-apoptotic signal. Consistent with the differential
      effect of ChoKIs in cancer and primary cells previously described, ChoKIs only
      promoted a transient and moderated ER stress response in the non-tumorogenic
      cells MCF10A. In conclusion, pharmacological inhibition of ChoKalpha induces
      cancer cell death through a mechanism that involves the activation of exaggerated
      and persistent ER stress supported by CHOP overproduction. 

PMID- 24287695
TI  - A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite
      mechanism for regulating myoblast proliferation and differentiation.
AB  - MiR-133 was found to be specifically expressed in cardiac and skeletal muscle in
      previous studies. There are two members in the miR-133 family: miR-133a and miR
      133b. Although previous studies indicated that miR-133a was related to
      myogenesis, the signaling pathways regulated by miR-133 were still not very
      clear. In this study, we showed that both miR-133a and miR-133b were upregulated
      during myogenesis through Solexa sequencing. We confirmed that miR-133 could
      promote myoblast differentiation and inhibit cell proliferation through the
      regulation of the extracellular signal-regulated kinase (ERK) signaling pathway
      in C2C12 cells. FGFR1 and PP2AC, which both participate in signal transduction of
      the ERK1/2 pathway, were found to be negatively regulated by miR-133a and miR
      133b at the post-transcriptional level. Also, downregulation of ERK1/2
      phosphorylation by miR-133 was detected. FGFR1 and PP2AC were also found to
      repress C2C12 differentiation by specific siRNAs. In addition, we found that
      inhibition of ERK1/2 pathway activity can inhibit C2C12 cell proliferation and
      promote the initiation of differentiation but form short and small myotubes.
      Furthermore, we found that the expression of miR-133 was negatively regulated by
      ERK1/2 signaling pathway. In summary, we demonstrated the role of miR-133 in
      myoblast and further revealed a new feedback loop between miR-133 and the ERK1/2
      signaling pathway involving an exquisite mechanism for regulating myogenesis. 

PMID- 24287696
TI  - The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63
      linked polyubiquitination of caspase-8.
AB  - Apoptosis resistance is a hurdle for cancer treatment. HECTD3, a new E3 ubiquitin
      ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase
      8 with K63-linked polyubiquitin chains that do not target caspase-8 for
      degradation but decrease the caspase-8 activation. HECTD3 depletion can sensitize
      cancer cells to extrinsic apoptotic stimuli. In addition, HECTD3 inhibits TNF
      related apoptosis-inducing ligand (TRAIL)-induced caspase-8 cleavage in an E3
      ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site
      at K215 abolishes the HECTD3 protection from TRAIL-induced cleavage. Finally,
      HECTD3 is frequently overexpressed in breast carcinomas. These findings suggest
      that caspase-8 ubiquitination by HECTD3 confers cancer cell survival. 

PMID- 24287697
TI  - Identification of DR5 as a critical, NF-kappaB-regulated mediator of Smac-induced
      apoptosis.
AB  - Smac mimetic promotes apoptosis by neutralizing inhibitor of apoptosis (IAP)
      proteins and is considered as a promising cancer therapeutic. Although an
      autocrine/paracrine tumor necrosis factor-alpha (TNFalpha) loop has been
      implicated in Smac mimetic-induced cell death, little is yet known about
      additional factors that determine sensitivity to Smac mimetic. Using genome-wide
      gene expression analysis, we identify death receptor 5 (DR5) as a novel key
      mediator of Smac mimetic-induced apoptosis. Although several cell lines that are
      sensitive to the Smac mimetic BV6 die in a TNFalpha-dependent manner, A172
      glioblastoma cells undergo BV6-induced apoptosis largely independently of
      TNFalpha/TNFR1, as the TNFalpha-blocking antibody Enbrel or TNFR1 knockdown
      provide little protection. Yet, BV6-stimulated nuclear factor-kappaB (NF-kappaB)
      activation is critically required for apoptosis, as inhibition of NF-kappaB by
      overexpression of dominant-negative IkappaBalpha superrepressor (IkappaBalpha-SR)
      blocks BV6-induced apoptosis. Unbiased genome-wide gene expression studies in
      IkappaBalpha-SR-overexpressing cells versus vector control cells reveal that BV6
      increases DR5 expression in a NF-kappaB-dependent manner. Importantly, this BV6
      stimulated upregulation of DR5 is critically required for apoptosis, as transient
      or stable knockdown of DR5 significantly inhibits BV6-triggered apoptosis. In
      addition, DR5 silencing attenuates formation of a RIP1/FADD/caspase-8 cytosolic
      cell death complex and activation of caspase-8, -3 and -9. By identifying DR5 as
      a critical mediator of Smac mimetic-induced apoptosis, our findings provide novel
      insights into the determinants that control susceptibility of cancer cells to
      Smac mimetic. 

PMID- 24287700
TI  - Isomerization of Asp7 leads to increased toxic effect of amyloid-beta42 on human
      neuronal cells.

PMID- 24287698
TI  - Differential regulation of the apoptotic machinery during megakaryocyte
      differentiation and platelet production by inhibitor of apoptosis protein Livin.
AB  - Livin is a member of the inhibitor of apoptosis proteins (IAP) family of
      intracellular antiapoptotic proteins that act by binding and inhibiting caspases.
      Upon strong apoptotic stimuli, it is then specifically cleaved by caspases to
      produce a truncated protein (tLivin) with a paradoxical proapoptotic activity.
      Intriguingly, we have detected robust protein levels of Livin in normal mature
      bone marrow megakaryocyte (MK) and platelets. To evaluate the potential role of
      Livin in thrombopoiesis, we used the human BCR-ABL+ cell line, LAMA-84, and cord
      blood CD34+ cells to induce differentiation toward MKs. Upon differentiation,
      induced by phorbol myristate acetate and concurrent with increase in Livin
      protein expression, LAMA-84 cells formed functional platelet-like particles.
      Livin overexpression in CD34+ progenitor cells induced higher endoreplication in
      the MKs generated. Furthermore, overexpression of Livin increased the ability of
      both primary MKs and differentiated LAMA-84 cells to produce functional
      platelets. In the differentiated LAMA-84 cells, we observed accumulation of
      proapoptotic tLivin concomitant with increased caspase-3 activity. Downregulation
      of Livin with small interfering RNA in both leukemic and primary MK cells
      decreased their ability to produce functional platelets. We suggest that Livin
      has a role in thrombopoiesis by regulating the apoptotic and antiapoptotic
      balance in MK endoreplication and platelet production. 

PMID- 24287701
TI  - Ligand mediated valence fluctuation of copper in new hybrid materials constructed
      from decavanadate and a Cu(1,10-phenanthroline) complex.
AB  - Two new organic hybrid materials [H4V10O28][CuCl(H2O)2(1,10
      phenanthroline)]2.4H2O (V10O28-CuCl-phen) and [H4V10O28][Cu(H2O)3(1,10
      phenanthroline)]2.4H2O (V10O28-CuO-phen) were synthesized at room temperature.
      The effect of the presence and absence of AlCl3 on the single crystal growth of
      the two compounds was studied. The compounds were characterized using single
      crystal X-ray diffraction (XRD), scanning electron microscopy, energy dispersive
      spectroscopy, infra-red spectroscopy and thermogravimetric analysis. XRD studies
      on selected single crystals suggest that the compounds consist of supramolecular
      3D layer structures constructed from a tetra-protonated [V10O28] unit and the
      organometallic complex Cu(1,10-phen) with Cl and 2H2O molecules in the presence
      of AlCl3 in V10O28-CuCl-phen and with 3H2O molecules in V10O28-CuO-phen which was
      confirmed by TGA studies. Both compounds crystallize in the triclinic space group
      P1[combining macron]: a = 8.3886(3) A, b = 10.4266(4) A, c = 13.5860(5) A, alpha
      = 92.440(2) degrees , beta = 92.315(2) degrees , gamma = 98.160(2) degrees  for
      V10O28-CuCl-phen and a = 8.3733(5) A, b = 10.4132(6) A, c = 13.5904(8) A, alpha =
      92.295(4) degrees , beta = 92.331(2) degrees , gamma = 98.086(4) degrees  for
      V10O28-CuO-phen. Magnetic measurements suggest that Cu exists in magnetic +2
      oxidation state in V10O28-CuCl-phen and non-magnetic +1 oxidation state in V10O28
      CuO-phen. 

PMID- 24287699
TI  - Expression of integrin alpha 10 is transcriptionally activated by pRb in mouse
      osteoblasts and is downregulated in multiple solid tumors.
AB  - pRb is known as a classic cell cycle regulator whose inactivation is an important
      initiator of tumorigenesis. However, more recently, it has also been linked to
      tumor progression. This study defines a role for pRb as a suppressor of the
      progression to metastasis by upregulating integrin alpha10. Transcription of this
      integrin subunit is herein found to be pRb dependent in mouse osteoblasts.
      Classic pRb partners in cell cycle control, E2F1 and E2F3, do not repress
      transcription of integrin alpha10 and phosphorylation of pRb is not necessary for
      activation of the integrin alpha10 promoter. Promoter deletion revealed a pRb
      responsive region between -108 bp to -55 bp upstream of the start of the site of
      transcription. pRb activation of transcription also leads to increased levels of
      integrin alpha10 protein and a greater concentration of the integrin alpha10
      protein at the cell membrane of mouse osteoblasts. These higher levels of
      integrin alpha10 correspond to increased binding to collagen substrate.
      Consistent with our findings in mouse osteoblasts, we found that integrin alpha10
      is significantly underexpressed in multiple solid tumors that have frequent
      inactivation of the pRb pathway. Bioinformatically, we identified data consistent
      with an 'integrin switch' that occurs in multiple solid tumors consisting of
      underexpression of integrins alpha7, alpha8, and alpha10 with concurrent
      overexpression of integrin beta4. pRb promotes cell adhesion by inducing
      expression of integrins necessary for cell adhesion to a substrate. We propose
      that pRb loss in solid tumors exacerbates aggressiveness by debilitating cellular
      adhesion, which in turn facilitates tumor cell detachment and metastasis. 

PMID- 24287702
TI  - Changes in spectral characteristics and copper (II)-binding of dissolved organic
      matter in leachate from different water-treatment processes.
AB  - The aim of the present study was to investigate the fluorescence properties of
      dissolved organic matter (DOM) from four leachate samples, which were disposed by
      regulating tank (RTK), anaerobic treatment (ATT), oxidation ditch (ODH), and
      membrane bioreactor and to assess their binding capacities and stability
      constants by Cu(II). The results showed that five fluorescent peaks, including
      three humic-like peaks (peaks A, C, and E) and two protein-like peaks (peaks B
      and D), were identified. Most fluorescent components can be degraded after ODH.
      Fluorescence-quenching titration showed that the modified Stern-Volmer model can
      be used to fit the quenching data and calculate conditional stability constants
      (log K) and the % of fluorophores (f %) between DOM and Cu(II). DOM-Cu(II)
      complexes had relatively high log K values in the RTK and ATT disposals. After
      the ODH-treatment process, log K values showed a marked decrease. The f % values
      of protein-like materials were evidently greater than those of humic-like
      substances. The results showed the impact of the water treatment on the metal
      binding ability of various fractions.

PMID- 24287703
TI  - Gridded field observations of polybrominated diphenyl ethers in soils of North
      China.
AB  - Polybrominated diphenyl ethers (PBDEs) were measured in 87 soil samples collected
      from North China. Eleven PBDE congeners (BDE28, 47, 49, 66, 99, 100, 119, 183,
      196, 203, and 209) were identified with a high frequency of detection (84-100 %)
      in soil samples, and their frequencies were used for statistical analysis in the
      present study. PBDE concentrations ranged from 0.08 to 8260 ng/g with a mean of
      202 ng/g, thus indicating severe pollution at these sample sites. BDE209 was the
      predominant congener with concentrations of 0.08-8140 ng/g (mean 188). Analysis
      of the spatial distribution of PBDEs in North China soils indicated that
      relatively high concentrations of both lower- and higher-brominated BDEs were
      present in Shandong Province, and a decreasing trend in PBDE concentrations from
      the east toward the west of North China was observed. Source identification
      analysis suggested that Jinghai County in Tianjin and the coastal area of Laizhou
      Bay, Shandong province, were the major sources in North China. The sources in
      Jinghai County were connected with the dismantling of electronic waste, whereas
      the sources in the coastal area of Laizhou Bay were connected with the production
      of PBDEs. Modeling results showed that the distance between the sampling sites
      and these point sources had a large influence on the transfer of PBDEs.

PMID- 24287704
TI  - Low-energy electron induced resonant loss of aromaticity: consequences on cross
      linking in terphenylthiol SAMs.
AB  - Aromatic self-assembled monolayers (SAMs) can be used as negative tone electron
      resists in functional surface lithographic fabrication. A dense and resistant
      molecular network is obtained under electron irradiation through the formation of
      a cross-linked network. The elementary processes and possible mechanisms involved
      were investigated through the response of a model aromatic SAM, p-terphenylthiol
      SAM, to low-energy electron (0-10 eV) irradiation. Energy loss spectra as well as
      vibrational excitation functions were measured using High Resolution Electron
      Energy Loss Spectroscopy (HREELS). A resonant electron attachment process was
      identified around 6 eV through associated enhanced excitation probability of the
      CH stretching modes nu(CH)(ph) at 378 meV. Electron irradiation at 6 eV was
      observed to induce a peak around 367 meV in the energy loss spectra, attributed
      to the formation of sp(3)-hybridized CHx groups within the SAM. This partial loss
      of aromaticity is interpreted to be the result of resonance formation, which
      relaxes by reorganization and/or CH bond dissociation mechanisms followed by
      radical chain reactions. These processes may also account for cross-linking
      induced by electron irradiation of aromatic SAMs in general.

PMID- 24287705
TI  - Ongoing challenges and recent advances in the prevention of mother-to-child
      transmission of HIV.

PMID- 24287706
TI  - Do cadmium, lead, and aluminum in drinking water increase the risk of hip
      fractures? A NOREPOS study.
AB  - The aim of this study was to investigate relations between cadmium, lead, and
      aluminum in municipality drinking water and the incidence of hip fractures in the
      Norwegian population. A trace metals survey in 566 waterworks was linked
      geographically to hip fractures from hospitals throughout the country (1994
      2000). In all those supplied from these waterworks, 5,438 men and 13,629 women
      aged 50-85 years suffered a hip fracture. Poisson regression models were fitted,
      adjusting for age, region of residence, urbanization, and type of water source as
      well as other possibly bone-related water quality factors. Effect modification by
      background variables and interactions between water quality factors were examined
      (correcting for false discovery rate). Men exposed to a relatively high
      concentration of cadmium (IRR = 1.10; 95 % CI 1.01, 1.20) had an increased risk
      of fracture. The association between relatively high lead and hip fracture risk
      was significant in the oldest age group (66-85 years) for both men (IRR = 1.11;
      95 % CI 1.02, 1.21) and women (IRR = 1.10; 95 % CI 1.04, 1.16). Effect
      modification by degree of urbanization on hip fracture risk in men was also found
      for all three metals: cadmium, lead, and aluminum. In summary, a relatively high
      concentration of cadmium, lead, and aluminum measured in drinking water increased
      the risk of hip fractures, but the associations depended on gender, age, and
      urbanization degree. This study could help in elucidating the complex effects on
      bone health by risk factors found in the environment.

PMID- 24287707
TI  - The sensitivity and specificity of transvaginal ultrasound with regard to acute
      pelvic inflammatory disease: a review of the literature.
AB  - PURPOSE: This review aims to sum up current knowledge on the sensitivity and
      specificity of ultrasound features suggestive of acute pelvic inflammatory
      disease (PID). METHODS: A PubMed database search was undertaken, using the MeSH
      terms "(pelvic inflammatory disease or salpingitis or adnexitis) and
      ultrasonography". We included original articles evaluating the performance of
      vaginal ultrasound in detecting acute PID. RESULTS: Seven articles were selected,
      including between 18 and 77 patients each. The golden standard used was
      laparoscopy/endometrial biopsy in six studies and mostly clinical evaluation in
      one. "Thick tubal walls" proved to be a specific and sensitive ultrasound sign of
      acute PID, provided that the walls of the tubes can be evaluated, i.e., when
      fluid is present in the tubal lumen (100 % sensitivity). The cogwheel sign is
      also a specific sign of PID (95-99 % specificity), but it seems to be less
      sensitive (0-86 % sensitivity). Bilateral adnexal masses appearing either as
      small solid masses or as cystic masses with thick walls and possibly manifesting
      the cogwheel sign also seems to be a reasonably reliable sign (82 % sensitivity,
      83 %specificity). Doppler results overlap too much between women with and without
      acute PID for them to be useful in the diagnosis of acute PID, even though
      acutely inflamed tubes are richly vascularized at color Doppler. CONCLUSIONS:
      Even though the results of our review suggest that transvaginal ultrasound has
      limited ability to diagnose acute PID, it is likely to be helpful when managing
      women with symptoms of acute PID, because in some cases the typical ultrasound
      signs of acute PID can be detected.

PMID- 24287708
TI  - Lightweight meshes: evaluation of mesh tissue integration and host tissue
      response.
AB  - INTRODUCTION: Differences in mesh composition may affect outcomes such as
      erosion, tissue integration and inflammation. The majority of commercially
      available meshes are type 1, manufactured from monofilament polypropylene with
      differing pore sizes and mechanical properties. OBJECTIVE: To assess the local
      tolerance of four commercially available meshes in terms of mesh integration and
      host tissue response. METHOD: Using an animal model, mesh was implanted onto the
      abdominal sheath. Animals were sacrificed at 7, 30 and 90 days and data
      collected. RESULTS: Strength of mesh-skin integration increased in all groups
      across the three time points. Polyform displayed highest strength of separation
      overall. VM PFR and Iprolite reached their maximum integration earliest. In
      regard to mesh abdominal wall integration Polyform had the greatest strength of
      separation, with Ultrapro displaying some weakening of integration at 30 and 90
      days. Host tissue response was similar in all groups at each time point.
      CONCLUSION: Polyform and VM PFR have enhanced tissue integration when compared to
      Ultrapro. This decreased integration in Ultrapro may lead to increased mesh
      failure. The composition of mesh affects its integration and potentially its
      failure rate but not host tissue response. These observations in mesh
      characteristics may benefit the design of next generation meshes with a view to
      reducing failure rates and erosion.

PMID- 24287709
TI  - Discrepancy of uterine leiomyoma and myometrium to hypoxia-induced endoplasmic
      reticulum stress after uterine occlusion therapy accounts for therapeutic effect.
AB  - PURPOSE: Uterine artery occlusion (UAO) is a promising method for the treatment
      of leiomyoma. This study is intended to demonstrate the discrepancy of ER stress
      induced apoptosis in leiomyoma and myometrium as a result of UAO therapy.
      METHODS: Primary cultured leiomyoma and myometrial cells were incubated in low
      oxygen supply (1 % O2). Then, real time RT-PCR and Western blotting were
      performed to analyze the mRNA and protein levels of ER stress-related molecules
      including GRP78, CHOP, JNK, Bax, Bcl-2 and Caspase4. Furthermore, the activity of
      Caspase4 was detected. Tissues of leiomyoma and myometria were also collected
      before and 30 min after UAO during surgery and evaluated. RESULTS: The leiomyoma
      cells and tissues expressed higher ER stress-related molecules compared to
      myometrial cells or tissues, while the levels of Bcl-2, an anti-apoptotic
      protein, declined. In myometrial cells, an elevated level of Caspase4 activation
      as well as its expression was not significant during the first 12 h, suggesting
      that hypoxia might not intensely affect the myometrium compared with leiomyoma.
      CONCLUSION: ER stress-related apoptosis partly accounts for the effects of UAO
      therapy on uterine leiomyoma, which leads to the death of leiomyoma while
      maintaining the survival of the uterus itself.

PMID- 24287710
TI  - Quality of life assessment of patients with scalp dermatitis using the Italian
      version of the Scalpdex.
AB  - The aim of this study was to assess quality of life in patients with scalp
      dermatitis using the Italian version of the Scalpdex, and to validate the
      instrument in Italian. The survey was conducted in outpatients with psoriasis,
      seborrhoeic dermatitis, alopecia, or follicular lichen. Data were completed on
      194 patients, 78% of whom had psoriasis. Scalpdex scores were always higher in
      women than in men, and in younger people compared to elderly people. The most
      frequent items were: being ashamed, embarrassed, bleeding scalp, feeling self
      conscious, bothered that the condition is incurable, having the choice of colour
      of clothes affected, having a negative effect on daily life. The Italian Scalpdex
      showed good internal consistency, test-retest reliability, convergent validity,
      and responsiveness. In conclusion, the Italian version of the Scalpdex is a
      useful instrument to measure quality of life in patients with a scalp condition.

PMID- 24287711
TI  - Identification of a disease complex involving a novel monopartite begomovirus
      with beta- and alphasatellites associated with okra leaf curl disease in Oman.
AB  - Okra leaf curl disease (OLCD) is an important viral disease of okra in tropical
      and subtropical areas. The disease is caused by begomovirus-satellite complexes.
      A begomovirus and associated betasatellite and alphasatellite were identified in
      symptomatic okra plants from Barka, in the Al-Batinah region of Oman. Analysis of
      the begomovirus sequences showed them to represent a new begomovirus most closely
      related to cotton leaf curl Gezira virus (CLCuGeV), a begomovirus of African
      origin. The sequences showed less than 85 % nucleotide sequence identity to
      CLCuGeV isolates. The name okra leaf curl Oman virus (OLCOMV) is proposed for the
      new virus. Further analysis revealed that the OLCOMV is a recombinant begomovirus
      that evolved by the recombination of CLCuGeV isolates with tomato yellow leaf
      curl virus-Oman (TYLCV-OM). An alpha- and a betasatellite were also identified
      from the same plant sample, which were also unique when compared to sequences
      available in the databases. However, although the betasatellite appeared to be of
      African origin, the alphasatellite was most closely related to alphasatellites
      originating from South Asia. This is the first report of a begomovirus-satellite
      complex infecting okra in Oman.

PMID- 24287712
TI  - Heart rates increase after hatching in two species of Natricine snakes.
AB  - Experimental studies have shown heart rates to decrease from embryo to hatchling
      stage in turtles, remain steady in skinks, and increase in birds. However, no
      snake species has been studied in this regard. I recorded heart rate evolution
      trajectories from embryo to juvenile stage in 78 eggs from two species of
      European Natricine snakes. Unexpectedly, snakes behaved more like birds than
      turtles or lizards: heart rates increased after hatching in both N. maura and N.
      natrix, respectively by 43.92 +/- 22.84% and 35.92 +/- 24.52%. Heart rate shift
      was not related to an abrupt elevation of metabolism per se (snakes that
      increased their heart rates the most sharply grew the least after birth), but
      rather due to a number of smaller eggs that experienced lower than normal heart
      rates throughout the incubation and recovered a normal heart rate post-birth.
      This finding is discussed in the light of hatching synchrony benefits. 

PMID- 24287713
TI  - Diagnostic performance of low-dose rest/stress Tc-99m tetrofosmin myocardial
      perfusion SPECT using the 530c CZT camera: quantitative vs visual analysis.
AB  - BACKGROUND: We set out to develop normal databases and prospectively validate
      abnormality criteria for a low-dose Tc-99m tetrofosmin myocardial perfusion SPECT
      protocol using the 530c CZT camera. METHODS: All patients received 6 mCi rest/20
      mCi stress doses of Tc-99m tetrofosmin. Rest and stress images were obtained over
      7-9 and 5-7 minutes according to the chest size. Low-dose CT of the chest was
      obtained on a standalone CT scanner. Forty patients with very low likelihood
      (LLK) of coronary artery disease (CAD) were used to define the normal count
      distributions. The abnormality criteria were prospectively validated in 55
      patients who had coronary angiography and in 40 patients with LLK of CAD.
      RESULTS: The results for quantitative non-attenuation-corrected (AC) and AC
      analysis and visual analysis were as follows: sensitivity of 79%, 85%, and 92% (P
      = NS) and specificity of 44%, 75%, and 56% (P = NS), respectively. The normalcy
      rates for quantitative non-AC and AC analyses and visual analysis were 95%, 98%,
      and 98% (P = NS). CONCLUSIONS: We have developed non-AC and AC normal databases
      for low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT protocol
      using the 530c CZT camera. The per-patient diagnostic performance of quantitative
      analyses is not significantly different from visual analysis by an experienced
      reader.

PMID- 24287714
TI  - Substituent effects on the turn-on kinetics of rhodamine-based fluorescent pH
      probes.
AB  - Fluorescent turn-on probes based on a rhodamine spirolactam (RSL) structure have
      recently become a popular means of detecting pH, metal ions, and other analytes
      of interest. RSLs are colorless and non-fluorescent until the target analyte
      induces opening of the spirocyclic ring system, revealing the fully conjugated
      and highly fluorescent rhodamine dye. Among RSLs opened by acid, we have observed
      wide variation in the kinetics of the fluorescence turn-on process such that some
      probes would not be usable in situations where a rapid reading is desired or the
      pH fluctuates temporally. Herein we present a systematic investigation of the
      fluorescence turn-on kinetics of RSLs to probe the hypothesis that the reaction
      rates are influenced by the electronic properties of the spirolactam ring system.
      A series of 8 aniline-derived RSLs with para substituents ranging from electron
      donating to electron-withdrawing was prepared from rhodamine B. The fluorescence
      turn-on rates are observed to increase by a factor of four as the substituent is
      tuned from methoxy to nitro. This effect is explained in terms of the
      destabilization of the reaction intermediate by the substituent. As the reaction
      rates increase across the series, a concomitant increase in fluorescence
      intensity is also observed. This result is attributed to an increase in the
      concentration of the fluorescent form of the dye and is consistent with the
      expected equilibrium properties of this system. These findings are applied to the
      design of a faster-reacting and more intensely fluorescent RSL pH probe. 

PMID- 24287715
TI  - A preliminary study on the effects of acute ethanol ingestion on default mode
      network and temporal fractal properties of the brain.
AB  - OBJECT: To study the effect of acute alcohol intoxication on the functional
      connectivity of the default mode network (DMN) and temporal fractal properties of
      the healthy adult brain. MATERIALS AND METHODS: Eleven healthy male volunteers
      were asked to drink 0.59 g/kg of ethanol. Resting state blood oxygen level
      dependent (rsBOLD) MRI scans were obtained before consumption, 60 min post
      consumption and 90 min post-consumption. Before each rsBOLD scan, pointed
      resolved spectroscopy (PRESS) (1)H-MRS (magnetic resonance spectroscopy) scans
      were acquired to measure ethanol levels in the right basal ganglia. RESULTS:
      Significant changes in DMN connectivity were found following alcohol consumption
      (p < 0.01). Both increased and decreased regional connectivity were found after
      60 min, whereas mostly decreased connectivity was found after 90 min. The fractal
      behaviour of the rsBOLD signal, which is believed to help reveal complexity of
      small-scale neuronal circuitry, became more ordered after both 60 and 90 min of
      alcohol consumption (p < 0.01). CONCLUSION: The DMN has been linked to personal
      identity and social behavior. As such, our preliminary findings may provide
      insight into the neuro-functional underpinnings of the cognitive and behavioral
      changes observed during acute alcohol intoxication. The reduced fractal dimension
      implies a change in function of small-scale neural networks towards less complex
      signaling.

PMID- 24287716
TI  - Ex vivo processing for maturation of Arabidopsis KDEL-tailed cysteine
      endopeptidase 2 (AtCEP2) pro-enzyme and its storage in endoplasmic reticulum
      derived organelles.
AB  - Ricinosomes are specialized ER-derived organelles that store the inactive pro
      forms of KDEL-tailed cysteine endopeptidases (KDEL-CysEP) associated with
      programmed cell death (PCD). The Arabidopsis genome encodes three KDEL-CysEP
      (AtCEP1, AtCEP2, and AtCEP3) that are differentially expressed in vegetative and
      generative tissues undergoing PCD. These Arabidopsis proteases have not been
      characterized at a biochemical level, nor have they been localized
      intracellularly. In this study, we characterized AtCEP2. A 3xHA-mCherry-AtCEP2
      gene fusion including pro-peptide and KDEL targeting sequences expressed under
      control of the endogenous promoter enabled us to isolate AtCEP2 "ex vivo". The
      purified protein was shown to be activated in a pH-dependent manner. After
      activation, however, protease activity was pH-independent. Analysis of substrate
      specificity showed that AtCEP2 accepts proline near the cleavage site, which is a
      rare feature specific for KDEL-CysEPs. mCherry-AtCEP2 was detected in the
      epidermal layers of leaves, hypocotyls and roots; in the root, it was
      predominantly found in the elongation zone and root cap. Co-localization with an
      ER membrane marker showed that mCherry-AtCEP2 was stored in two different types
      of ER-derived organelles: 10 MUm long spindle shaped organelles as well as round
      vesicles with a diameter of approximately 1 MUm. The long organelles appear to be
      ER bodies, which are found specifically in Brassicacae. The round vesicles
      strongly resemble the ricinosomes first described in castor bean. This study
      provides a first evidence for the existence of ricinosomes in Arabidopsis, and
      may open up new avenues of research in the field of PCD and developmental tissue
      remodeling.

PMID- 24287717
TI  - A half-century analysis of landscape dynamics in southern Quebec, Canada.
AB  - We studied landscape dynamics for three time periods (<1950, 1965, and 1997)
      along a gradient of agricultural intensity from highly intensive agriculture to
      forested areas in southern Quebec. Air photos were analyzed to obtain long-term
      information on land cover (crop and habitat types) and linear habitats (hedgerows
      and riparian habitats) and landscape metrics were calculated to quantify changes
      in habitat configuration. Anthropogenic areas increased in all types of
      landscapes but mostly occurred in the highly disturbed cash crop dominated
      landscape. Perennial crops (pasture and hayfields) were largely converted into
      annual crops (corn and soybean) between 1965 and 1997. The coalescence of annual
      crop fields resulted in a more homogeneous agricultural landscape. Old fields and
      forest cover was consistently low and forest fragmentation remained stable
      through time in the intensive agriculture landscapes. However, forest cover
      increased and forest fragmentation receded in the forest-dominated landscapes
      following farm abandonment and the transition of old fields into forests. Tree
      dominated hedgerows and riparian habitats increased in areas with intensive
      agriculture. Observed changes in land cover classes are related to proximate
      factors, such as surficial deposits and topography. Agriculture intensification
      occurred in areas highly suitable for agriculture whereas farm abandonment was
      observed in poor-quality agriculture terrains. Large-scale conversion of
      perennial crops into annual crops along with continued urbanization exerts strong
      pressures on residual natural habitats and their inhabiting wildlife. The
      afforestation process occurring in the more forested landscapes along with the
      addition of tree-dominated hedgerows and riparian habitats in the agriculture
      dominated landscapes should improve landscape ecological value. 

PMID- 24287718
TI  - Dissipation kinetics, safety evaluation, and assessment of pre-harvest interval
      (PHI) and processing factor for kresoxim methyl residues in grape.
AB  - A field dissipation study was conducted to evaluate the pre-harvest interval
      (PHI) and processing factor (PF) for kresoxim methyl (Ergon 44.3 SC) residues in
      grapes and during raisin making process at recommended dose (RD) and double the
      recommended dose (DRD). Kresoxim methyl residues dissipated following 1st-order
      kinetics with a half-life of 10 and 18 days at RD and DRD, respectively. The PHIs
      with respect to the European Union maximum residue limit (EU-MRL) of 1 mg kg(-1)
      for grapes were 13 and 30 days at RD and DRD, respectively. The degradation data
      during grape to raisin making process were best fitted to nonlinear 1st + 1st
      order kinetics with a half-life ranging between 4 and 8 days for both shade
      drying and with raisin dryer at different doses. The PFs were 1.19 and 1.24 with
      shade drying and 1.09 and 1.10 with raisin dryer, respectively, which indicates
      concentration of the residues during raisin making process. The dietary exposure
      of kresoxim methyl on each sampling day was less than the respective maximum
      permissible intake both at RD and DRD. The residues of kresoxim methyl in market
      samples of grapes and raisins were well below the EU-MRL and were also devoid of
      any risk of acute toxicity related to dietary exposure.

PMID- 24287721
TI  - Fifteen-second skin icing using a frozen gel pack is effective for reducing
      goserelin injection pain.
AB  - OBJECTIVE: The efficacy of skin icing to reduce the pain of goserelin injection
      has been reported. We investigated the optimal icing time with a frozen gel pack
      and its effectiveness. METHODS: Abdominal skin temperatures of 49 healthy
      volunteers were measured after application of the frozen gel pack for 10, 15 and
      30 s, and it was decided that a 15-second icing was adequate. For 55 consecutive
      patients who received goserelin (10.8 mg) injection, pain was evaluated employing
      a visual analog scale (VAS). The first injection was administered routinely. A
      second injection was administered after skin icing in 27 of 55 patients who
      wanted to try icing. At the time of the third injection, all patient decided
      whether they were to receive icing or the routine method. RESULTS: After icing,
      VAS scores decreased in 20 of 27 patients. At the third injection, 18 patients
      requested icing. CONCLUSION: When a patient complains of injection pain, the
      icing method should be considered for pain reduction.

PMID- 24287720
TI  - Rapid anxiolytic effects of a 5-HT4 receptor agonist are mediated by a
      neurogenesis-independent mechanism.
AB  - Selective serotonin reuptake inhibitors (SSRIs) display a delayed onset of action
      of several weeks. Past work in naive rats showed that 5-HT4 receptor agonists had
      rapid effects on depression-related behaviors and on hippocampal neurogenesis. We
      decided to investigate whether 5-HT4 receptor stimulation was necessary for the
      effects of SSRIs in a mouse model of anxiety/depression, and whether hippocampal
      neurogenesis contributed to these effects. Using the mouse corticosterone model
      of anxiety/depression, we assessed whether chronic treatment with a 5-HT4
      receptor agonist (RS67333, 1.5 mg/kg/day) had effects on anxiety- and depression
      related behaviors, as well as on hippocampal neurogenesis in comparison with
      chronic fluoxetine treatment (18 mg/kg/day). Then, using our anxiety/depression
      model combined with ablation of hippocampal neurogenesis, we investigated whether
      neurogenesis was necessary for the behavioral effects of subchronic (7 days) or
      chronic (28 days) RS67333 treatment. We also assessed whether a 5-HT4 receptor
      antagonist (GR125487, 1 mg/kg/day) could prevent the behavioral and neurogenic
      effects of fluoxetine. Chronic treatment with RS67333, similar to fluoxetine,
      induced anxiolytic/antidepressant-like activity and stimulated adult hippocampal
      neurogenesis, specifically facilitating maturation of newborn neurons. However,
      unlike fluoxetine, anxiolytic effects of RS67333 were already present after 7
      days and did not require hippocampal neurogenesis. Chronic treatment with
      GR125487 prevented both anxiolytic/antidepressant-like and neurogenic effects of
      fluoxetine, indicating that 5-HT4 receptor activation is necessary for these
      effects of SSRIs. 5-HT4 receptor stimulation could represent an innovative and
      rapid onset therapeutic approach to treat depression with comorbid anxiety.

PMID- 24287724
TI  - [Is there a way to improve the situation at the Department of Internal Medicine
      at Landspitali The National University Hospital? A Consultant's point of view
      [Editorial]].

PMID- 24287719
TI  - Evidence for a role of transporter-mediated currents in the depletion of brain
      serotonin induced by serotonin transporter substrates.
AB  - Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4
      methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while
      certain other substrates do not. The 5-HT deficits produced by SERT substrates
      are dependent upon transporter proteins, but the exact mechanisms responsible are
      unclear. Here, we compared the pharmacology of several SERT substrates:
      fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m
      trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between
      acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo
      microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT
      release and long-term depletion in the same subjects. In vitro assays were
      performed to measure efflux of [(3)H]5-HT in rat brain synaptosomes and
      transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When
      administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce
      large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects
      on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine
      and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke
      fluoxetine-sensitive efflux of [(3)H]5-HT from synaptosomes, but d-fenfluramine
      and its bioactive metabolite d-norfenfluramine induce significantly greater SERT
      mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT
      release probably does not mediate 5-HT depletion. However, the magnitude of
      transporter-mediated inward current may be a critical factor in the cascade of
      events leading to 5-HT deficits. This hypothesis warrants further study,
      especially given the growing popularity of designer drugs that target SERT.

PMID- 24287722
TI  - Assessment of intravenous pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) in yucatan
      swine.
AB  - PDX1 (pancreatic and duodenal homeobox 1) is overexpressed in pancreatic cancer,
      and its reduction results in tumor regression. Bi-functional pbi-shRNA PDX1
      nanoparticle (OFHIRNA-PDX1) utilizes the endogenous micro-RNA biogenesis pathway
      to effect cleavage- and non-cleavage-dependent degradation of PDX1 mRNA. We have
      shown that OFHIRNA-PDX1 reduces pancreatic tumor volume in xenograft models.
      Thus, we are now exploring biorelevant large animal safety of OFHIRNA-PDX1. Mini
      pigs were chosen as the biorelevant species based on the similarity of human and
      pig PDX1 target sequence. In the initial study, animals developed fever,
      lethargy, hyporexia and cutaneous hyperemia following administration of OFHIRNA
      PDX1. Twenty-one days later, the same animals demonstrated less toxicity with a
      second OFHIRNA-PDX1 infusion in conjunction with a prophylactic regimen involving
      dexamethasone, diphenhydramine, Indocin and ranitidine. In a new group of
      animals, PDX1 protein (31 kDa) expression in the pancreas was significantly
      repressed at 48 and 72 h (85%, P=0.018 and 88%, P=0.013; respectively) following
      a single infusion of OFHIRNA-PDX1 but recovered to normal state within 7 days. In
      conclusion, a single intravenous infusion of OFHIRNA-PDX1 in conjunction with
      premedication in pigs was well tolerated and demonstrated significant PDX1
      knockdown. 

PMID- 24287723
TI  - Electrotransfer of single-stranded or double-stranded DNA induces complete
      regression of palpable B16.F10 mouse melanomas.
AB  - Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been
      confirmed in many preclinical models. Intratumor electrotransfer of plasmids
      encoding therapeutic molecules has reached Phase II clinical trials. In multiple
      preclinical studies, a reduction in tumor growth, increased survival or complete
      tumor regression have been observed in control groups in which vector or backbone
      plasmid DNA electrotransfer was performed. This study explores factors that could
      produce this antitumor effect. The specific electrotransfer pulse protocol
      employed significantly potentiated the regression. Tumor regression was observed
      after delivery of single-stranded or double-stranded DNA with or without CpG
      motifs in both immunocompetent and immunodeficient mice, indicating the
      involvement of the innate immune system in response to DNA. In conclusion, this
      study demonstrated that the observed antitumor effects are not due to a single
      factor, but to a combination of factors. 

PMID- 24287725
TI  - [What is the cause of crisis in internal medicine? [Editorial]].

PMID- 24287726
TI  - [The incidence and mortality of ARDS at Landspitali - The National University
      Hospital of Iceland 2004-2008].
AB  - OBJECTIVE: A retrospective study of the incidence, causes, mortality and
      treatment of patients with ARDS at Landspitali The National University Hospital
      of Iceland during the five year period 2004-2008 and comparing the results with
      an earlier study for the period 1988-1997. MATERIALS AND METHODS: All ICU
      admissions during the period 2004-2008 were reviewed, selecting patients
      according to the American-European consensus criteria for ARDS. Data were
      collected on age, gender, causes, length of stay, ventilator treatment and
      survival. RESULTS: A total of 6413 patients were admitted to the ICUs at
      Landspitali during the study period and 120 patients were found to have ARDS
      giving an incidence of 7,9/100.000 inhabitants. Average age was 55 years, 55%
      were males, length of stay was 13 days and hospital stay 24 days. ICU mortality
      was 30% and 90 day mortality was 39%. CONCLUSION: The incidence of ARDS seems to
      have increased some-what during the period 1988-1997. Mortality has decreased
      significantly probably due to improvements in intensive care treatment,
      especially ventilator treament with the use of lung protective ventilation, high
      frequency oscillation, prone position and ECMO.

PMID- 24287727
TI  - [Spinal cord infarction].
AB  - Spinal cord infarction is a rare disease. The disorder is well known as a result
      of aorta atherosclerosis or complication of aorta surgery. The disorder can mimic
      other diseases and be difficult to diagnose. We describe a special case of a
      patient with idiopathic spinal cord infarction. Symptoms and prognosis of the
      disorder will also be discussed. Key words: Spinal cord infarct, case report,
      MRI, spinal cord diseases.

PMID- 24287728
TI  - N-heterocyclic carbenes as effective ligands for the preparation of stabilized
      copper- and silver-t-butylthiolate clusters.
AB  - The ligation of N-heterocyclic carbenes (NHCs) to [CuS(t)Bu] and [AgS(t)Bu] was
      developed as an alternative to PR3 ligands as solubilizing reagents for these
      coordination polymers in order to form polynuclear copper and silver t
      butylthiolate clusters. 1,3-Di-isopropylbenzimidazol-2-ylidene ((i)Pr2-bimy) and
      1,3-di-isopropyl-4,5-dimethylimidazol-2-ylidene ((i)Pr2-mimy) were ligated to
      [CuS(t)Bu] and [AgS(t)Bu] forming [Cu4(S(t)Bu)4((i)Pr2-bimy)2] 1,
      [Cu4(S(t)Bu)4((i)Pr2-mimy)2] 2, [Ag4(S(t)Bu)4((i)Pr2-bimy)2] 5 and
      [Ag5(S(t)Bu)6][Ag((i)Pr2-mimy)2] 6. For comparison, the trialkyl phosphines
      P(n)Pr3 and P(i)Pr3 were also used to solubilize [AgS(t)Bu] and [CuS(t)Bu] to
      form copper and silver t-butylthiolate clusters. [Cu4(S(t)Bu)4(P(n)Pr3)2] 3,
      [Cu4(S(t)Bu)4(P(i)Pr3)2] 4, [Ag4(S(t)Bu)4(P(n)Pr3)2] 7 and
      [Ag6(S(t)Bu)6(P(i)Pr3)2] 8 were thus formed upon reaction with [CuS(t)Bu] and
      [AgS(t)Bu]. The synthesized complexes have been characterized via spectroscopic
      and crystallographic methods. The molecular structures of the clusters, which can
      vary according to the ligand type, are described.

PMID- 24287730
TI  - Donor mesenchymal stromal cells (MSCs) undergo variable cardiac reprogramming in
      vivo and predominantly co-express cardiac and stromal determinants after
      experimental acute myocardial infarction.
AB  - We previously showed the emergence of predominantly non-fused murine cells co
      expressing cardiac and stromal determinants in co-cultures of murine mesenchymal
      stromal cells (MSCs) and rat embryonic cardiomyocytes. To determine whether a
      similar phenotype is detectable in vivo in ischemic myocardium, we infused green
      fluorescence protein (GFP)-marked MSCs intravenously into wild-type mice in an
      acute myocardial infarction (AMI) model generated by ischemia/reperfusion (I/R)
      or fixed coronary artery ligation. We found that infused GFP+ cells were confined
      strictly to ischemic areas and represented approximately 10% of total
      cellularity. We showed that over 60% of the cells co-expressed collagen type IV
      and troponin T or myosin heavy chain, characteristic of MSCs and cardiomyocytes,
      respectively, and were CD45(-). Nonetheless, up to 25% of the GFP+ donor cells
      expressed one of two cardiomyocyte markers, either myosin heavy chain or troponin
      T, in the absence of MSC determinants. We also observed a marked reduction in
      OCT4 expression in MSCs pre-infusion compared with those lodged in the
      myocardium, suggesting reduced stem cell properties. Despite the low frequency of
      lodged donor MSCs, left-ventricular end-diastolic pressure was significantly
      better in experimental versus saline animals for both AMI (12.10 +/- 1.81 vs.
      20.50 +/- 1.53 mmHg, p < 0.001) and I/R models (8.75 +/- 2.95 vs. 17.53 +/- 3.85
      mmHg, p = 0.004) when measured 21 days after MSC infusion and is consistent with
      a paracrine effect. Our data indicate that donor MSCs undergo variable degrees of
      cardiomyocyte reprogramming with the majority co-expressing cardiomyocyte and
      stromal markers. Further studies are needed to elucidate the factors mediating
      the extent of cardiomyocyte reprogramming and importance of the cellular changes
      on tissue repair.

PMID- 24287732
TI  - Interfacial reaction of water ice on polycrystalline vanadium and its effects on
      thermal desorption of water.
AB  - Thermal desorption and decomposition of water ice deposited onto a
      polycrystalline V surface were investigated using temperature-programmed
      desorption and secondary ion mass spectrometry. The water molecules in multilayer
      films dissociate preferentially at the interface, whereas water desorption from
      the surface is depressed considerably. The oxygen atoms (hydrogen molecules)
      formed at the interface are incorporated into the substrate (released into the
      gas phase) sequentially at temperatures higher than 140 K. The crystallization
      kinetics of water multilayers is not influenced by the interfacial reaction, but
      the water desorption rate is depressed by the interfacial reaction even after
      crystallization. Consequently, thermal desorption of water from the surface and
      its reaction at the interface are found to be correlated across thin films. This
      behavior is explainable as dynamic heterogeneity of water in the deeply
      supercooled region and premelting of metastable ice Ic, where mobile water
      molecules play a dominant role in both thermal desorption and the interfacial
      reaction. 

PMID- 24287734
TI  - Catalytic stereodivergent functionalization of H2@C60.
AB  - A complete stereocontrol of 1,3-dipolar cycloaddition of N-metalated azomethine
      ylides onto endohedral fullerene H2@C60 is reported for the first time. The
      stereodivergent synthesis of either the cis or the trans endohedral cycloadduct
      is achieved with excellent diastereo- and enantioselectivities. 

PMID- 24287733
TI  - The prevalence of skin disorders in Norwegian paediatric renal transplant
      recipients.
AB  - A few key publications report on the frequency of skin disorders in paediatric
      organ transplant recipients in Southern and Central Europe presenting cumulative
      incidences. We aimed to estimate frequencies of skin disorders both as cumulative
      incidences and prevalence data, and describe skin problems in paediatric renal
      transplant recipients in a Norwegian renal transplant population. Clinical
      examination and review of post-transplant skin diseases were conducted in 70
      patients having performed renal transplantation before the age of 16 in the
      period 1983-2006. Viral warts were a common and persistent problem, whereas
      bacterial and fungal infections in the skin were few. Drug-related skin disorders
      were rather frequent, but usually reversible on dose reduction or change of
      medication. Pre-malignant and malignant skin disorders appeared only in patients
      > 30 years of age. Relatively high cumulative incidences and low prevalence data
      of most skin disorders were found in the examined patient cohort.

PMID- 24287731
TI  - Gene expression in superior temporal cortex of schizophrenia patients.
AB  - We investigated gene expression pattern obtained from microarray data of 10
      schizophrenia patients and 10 control subjects. Brain tissue samples were
      obtained postmortem; thus, the different ages of the patients at death also
      allowed a study of the dynamic behavior of the expression patterns over a time
      frame of many years. We used statistical tests and dimensionality reduction
      methods to characterize the subset of genes differentially expressed in the two
      groups. A set of 10 genes were significantly downregulated, and a larger set of
      40 genes were upregulated in the schizophrenia patients. Interestingly, the set
      of upregulated genes includes a large number of genes associated with gene
      transcription (zinc finger proteins and histone methylation) and apoptosis. We
      furthermore identified genes with a significant trend correlating with age in the
      control (MLL3) or the schizophrenia group (SOX5, CTRL). Assessments of
      correlations of other genes with the disorder (RRM1) or with the duration of
      medication could not be resolved, because all patients were medicated. This
      hypothesis-free approach uncovered a series of genes differentially expressed in
      schizophrenia that belong to a number of distinct cell functions, such as
      apoptosis, transcriptional regulation, cell motility, energy metabolism and
      hypoxia.

PMID- 24287735
TI  - The use of actigraphy in the monitoring of methylphenidate versus placebo in
      ADHD: a meta-analysis.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder of childhood. There is an increasing need to find
      objective measures and markers of the disorder in order to assess the efficacy of
      the therapy and to improve follow-up strategies. Actigraphy is an objective
      method for recording motor activity and sleep parameters using small,
      computerized, watch-like devices worn on the body, and it has been used in many
      clinical trials to assess methylphenidate efficacy and adverse effects in ADHD.
      Our article aim is to systematically review and perform a meta-analysis of the
      current evidence on the role of actigraphy in both the detection of changes in
      activity and in sleep patterns in randomized clinical trials that compared
      methylphenidate against placebo in the treatment of ADHD. A comprehensive
      literature search of PubMed/MEDLINE, Scopus, Embase, Cochrane Library, CINHAL and
      PsycINFO databases was carried out to find randomized clinical trials comparing
      methylphenidate versus placebo in children with ADHD, using actigraphic measures
      as an outcome. No start date limit was used and the search was updated until June
      2013. The primary outcome measures were 'total sleep time' and daytime 'activity
      mean'. As secondary outcomes, we analyzed 'sleep onset latency', 'sleep
      efficiency' and 'wake after sleep onset'. Eight articles comprising 393 patients
      were included in the analysis. Children with ADHD using MPH compared to placebo
      have a significant difference of a large effect with a diminishing value in the
      activity mean. For the total sleep time, we found a significant and large effect
      in the decrease in sleep in MPH group. This study shows that MPH may effectively
      reduce mean activity in ADHD children, but it may negatively affect total sleep
      time. 

PMID- 24287736
TI  - Micro-scaffold array chip for upgrading cell-based high-throughput drug testing
      to 3D using benchtop equipment.
AB  - Cell-based high throughput drug screening accelerates the pace of drug discovery
      which is routinely operated on planar high-density multi-well plates with
      sophisticated robotic liquid-dispensing systems for cell seeding and drug
      administration. Considerable efforts have been made to upgrade in vitro cellular
      models from 2D to a more biomimetic 3D configuration. For instance, in anti
      cancer drug screening, tumor spheroids are increasingly applied as a gold
      standard 3D model exhibiting cellular behaviors and drug responses
      distinguishable from the 2D counterpart. However, translation of spheroids to
      high throughput drug screening is challenging since pre-formation of spheroids
      and subsequent translocation to multi-well plates for drug testing are usually
      uncontrollable and time/reagent consuming and cell loss is inevitable during
      medium exchange for drug testing. Here we present an off-the-shelf micro-scaffold
      array chip which enables high throughput 3D cell culture, drug administration and
      quantitative in situ assays entirely on the same chip. The sponge-like micro
      scaffolds functioned both as absorbents to realize parallel auto-loading of cells
      or drugs and as barriers to prevent cell loss during medium exchange via
      centrifugation. Rapid manual loading of cell suspensions or drugs into the 96
      isolated micro-scaffolds on the chip was achieved in the timescale of several
      seconds, meanwhile with total medium consumption reduced to the order of
      microliters. Proof of concept demonstration of drug cytotoxicity testing was
      performed on multiple cancer cells using common benchtop equipment, making it
      accessible to most biomedical labs with basic cell culture setups. Higher
      cellular drug resistance was constantly obtained with this platform compared to
      the planar cultures, which was partially attributed to the malignant phenotype of
      cancer cells yielded by enhanced cell-matrix interactions in the micro-scaffolds.
      Interestingly, the high drug resistance of 3D cultured cells in the micro
      scaffold was shown to be density-independent in contrast to the density-dependent
      drug response for 2D cultured cells, indicating intrinsic differences between the
      two culture models. This platform is expected to facilitate upgrade of the
      current cell-based high throughput drug testing to the 3D level and be widely
      applicable across various disciplines. 

PMID- 24287737
TI  - [Age and earnings of specialists[Editorial]].

PMID- 24287738
TI  - [A new approach in treatment of mental disorders. Teamwork and specific
      treatments[Editorial]].

PMID- 24287739
TI  - [Epidemiology of acute kidney injury in a tertiary care university hospital
      according to the RIFLE criteria].
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common problem in hospitalized
      patients, requiring extensive treatment and carries a high mortality rate. This
      study was designed to assess the epidemiology of AKI, and risk factors and
      outcome of patients with severe AKI in a tertiary care university hospital in
      Iceland. MATERIAL AND METHODS: All adult patients with measured serum creatinine
      (SCr) in Landspitali University Hospital from January 2008 to December 2011, who
      had a measured baseline SCr in the preceeding six months, were included. Patients
      were categorized according to the RIFLE-criteria into risk (stage 1), injury
      (stage 2) and failure (stage 3) groups based on their highest SCr, using the
      lowest SCr in the previous six months as baseline. RESULTS: A total of 17,693
      individuals (out of 74,960) had a baseline SCr and their data were used for
      analysis. AKI occurred in 3,686 (21%) with 12%, 5% and 4% of stage 1, 2 and 3,
      respectively. There were more females in stage 1 and stage 2 and more males in
      stage 3 (p< 0.001). Contributing causes for AKI in patients with stage 3 AKI were
      surgery (22%), circulatory shock (23%), sepsis (14%), cardiovascular insult
      (32%), respiratory failure (27%), bleeding (10%), trauma (7%) and AKI associated
      drugs (61%). Dialysis was required in 11% and in 0.7% for longer than 30 days but
      none > 90 days. One year survival was 52%. CONCLUSIONS: Acute kidney injury is
      common in Iceland and the prognosis of those with severe AKI is dismal. Majority
      of those patients were taking drugs that increase risk of AKI, providing a target
      for preventive measures.

PMID- 24287740
TI  - [The effect of antidepressants and sedatives on the efficacy of transdiagnostic
      cognitive behavioral therapy in groups in primary care].
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) and SSRI/SNRI antidepressants have
      proven to be effective treatments for anxiety and depression. The gain from
      combined CBT and antidepressant therapy has in some studies been greater than
      from monotherapy. Benzodiazepines may interfere with the efficacy of individual
      CBT-treatment. We examined the effects of SSRI/SNRI antidepressants and the
      effects of benzodiazepines/z-drugs on the efficacy of group CBT (gCBT) in primary
      care. MATERIAL AND METHODS: Primary outcome measures were the Beck's Depression
      Inventory II (BDI-II) and the Beck's Anxiety Inventory (BAI) scores before
      treatment and after the last session. The last observed score was carried forward
      and compared to the initial score for each individual, irrespective of the timing
      of the last score (LOCF). Mean change of scores was compared between groups of
      individuals on or not on SSRI/SNRI antidepressants and/or benzodiazepines/z
      drugs. RESULTS: Over three years 557 subjects participated in a 5 week-long gCBT.
      Of these 355 returned BDI-II and 350 returned BAI at least twice. The mean score
      on SSRI/SNRI or benzo/z-drugs fell significantly both for those on combined
      treatment (medication and gCBT) and those who only received gCBT. Combined
      treatment with SSRI/SNRI and gCBT led to a greater fall in depressive symptoms
      compared to gCBT monotherapy. The efficacy of such combined treatment was less
      for those who also were prescribed benzodiazepines and/or z-drugs. CONCLUSIONS:
      Group CBT significantly improved symptoms of anxiety and depression in primary
      care. The improvement was not reduced by concomitant use of SSRI/SNRI
      antidepressants nor of benzodiazepines/z-hypnotics. The use of such medication is
      therefore not contraindicated for gCBT participants, at least not short term.
      Adding SSRIs or SNRIs to gCBT led to greater efficacy in reducing depressive
      symptom though the efficacy of such combined treatment was less for those who
      were also prescribed benzodiazepines and/or z-hypnotics.

PMID- 24287741
TI  - [A female in her forties with dysphagia and chest pain. Esophageal leiomyoma.
      Case of the month].

PMID- 24287742
TI  - Sub-micrometer-precision, three-dimensional (3D) hydrodynamic focusing via
      "microfluidic drifting".
AB  - In this article, we demonstrate single-layered, "microfluidic drifting" based
      three-dimensional (3D) hydrodynamic focusing devices with particle/cell focal
      positioning approaching submicron precision along both lateral and vertical
      directions. By systematically optimizing channel geometries and sample/sheath
      flow rates, a series of "microfluidic drifting" based 3D hydrodynamic focusing
      devices with different curvature angles are designed and fabricated. Their
      performances are then evaluated using confocal microscopy, fast camera imaging,
      and side-view imaging techniques. Using a device with a curvature angle of 180
      degrees , we have achieved a standard deviation of +/-0.45 MUm in particle focal
      position and a coefficient of variation (CV) of 2.37% in flow cytometric
      measurements. To the best of our knowledge, this is the best CV that has been
      achieved using a microfluidic flow cytometry device. Moreover, the device showed
      the capability to distinguish 8 peaks when subjected to a stringent 8-peak
      rainbow calibration test, signifying the ability to perform sensitive, accurate
      tests similar to commercial flow cytometers. We have further tested and validated
      our device by detection of HEK-293 cells. With its advantages in simple
      fabrication (i.e., single-layered device), precise 3D hydrodynamic focusing
      (i.e., submicrometer precision along both lateral and vertical directions), and
      high detection resolution (i.e., low CV), our method could serve as an important
      basis for high-performance, mass-producible microfluidic flow cytometry. 

PMID- 24287744
TI  - On the linear and non-linear electronic spectroscopy of chlorophylls: a
      computational study.
AB  - A theoretical analysis of linear and non-linear (two-photon absorption)
      electronic spectroscopy of all known porphyrinic pigments has been performed
      using linear and quadratic density functional response theory, with the long
      range corrected CAM-B3LYP functional. We found that higher Soret transitions
      often contain non-Gouterman contributions and that each chlorophyll has the
      possibility for resonance enhanced TPA in the Soret region, although there is
      also significant TPA in the Q region. 

PMID- 24287743
TI  - Role of met axis in head and neck cancer.
AB  - Head and neck cancer is the sixth most common type of cancer worldwide. Despite
      advances in aggressive multidisciplinary treatments, the 5-year survival rate for
      this dreadful disease is only 50%, mostly due to high rate of recurrence and
      early involvement of regional lymph nodes and subsequent metastasis.
      Understanding the molecular mechanisms responsible for invasion and metastasis is
      one of the most pressing goals in the field of head and neck cancer. Met, also
      known as hepatocyte growth factor receptor (HGFR), is a member of the receptor
      protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis
      is dysregulated and plays important roles in tumorigenesis, progression,
      metastasis, angiogenesis, and drug resistance in head and neck cancer. We
      describe in this review current understanding of Met axis in head and neck cancer
      biology and development of therapeutic inhibitors targeting Met axis. 

PMID- 24287746
TI  - Pattern of dermatoses among inmates of Ilesha Prison, Nigeria.
AB  - AIMS AND OBJECTIVES: Dermatoses are common health problems in prisons and
      environmental conditions influence their prevalence and pattern. Hot and humid
      environment as obtains in the tropics, stress, and overcrowding are conditions
      that facilitate development of. The aim of this study was to determine the
      prevalence and pattern of dermatoses in a prison located in a tropical
      environment. MATERIALS AND METHODS: The study was done in May-July 2006 in a
      South-West Nigerian prison. Using a purpose designed questionnaire, information
      on sex, age, prison status, and number in rooms was obtained and inmates were
      clinically examined. RESULTS: Inmates studied were 305 (296 males and 9 females).
      Dermatoses were found in 221 inmates with overall prevalence of 72.5% (221/305).
      Infectious disorders were seen in 67.9% (150/221) and non-infectious in 32.1%
      (71/221). The diseases occurred in 72.9% (167/229) of awaiting trial persons and
      72.9% (51/70) convicted persons. Overcrowding was more in cells (average sleeping
      area was 9.5 sq feet). Skin diseases affected 80.3% (61/76) of inmates in cells
      and 69.9% (160/229) in dormitory rooms.. About 71.2% (94/132) of inmates affected
      stay in five highly overcrowded dormitory rooms with infectious disorders in
      48.5% (64/132). Dermatophyte infections were 34.3% of 332 dermatoses seen,
      pityriasis versicolor 14.5%, acne vulgaris 12.3%, dandruff 10.5%, 28.4%. A
      significant relationship was found with overcrowding and place where dermatoses
      were first noticed. CONCLUSION: Dermatoses are common health problem of
      prisoners, and prison conditions facilitate these problems.

PMID- 24287745
TI  - Health status of children in institutionalised homes in South West Nigeria.
AB  - AIMS AND OBJECTIVES: To determine the nutritional and immunisation status as well
      as morbidity pattern of children in institutionalised care in south-western
      Nigeria. SUBJECTS AND METHODS: The study was cross sectional and involved
      children under the age of fifteen years in seven institutions in Oyo and Ogun
      states, south western Nigeria. Children admitted into these homes were either
      orphans or those separated from their parents through child abandonment, illness
      and juvenile delinquency. A history of current and recent illnesses in the
      preceding one month as well as immunisation was obtained for each child. Physical
      examination including growth assessment was then performed after which blood
      specimens were collected for haematocrit estimation, haemoglobin electrophoresis
      and examination for malaria parasites. RESULTS: A total of 161 children were
      studied comprising 74 (46.0%) males and 87 (54.0%) females. Their ages ranged
      from 1.12 to 168 months with a mean (standard deviation) of 94.5 (47.0) months.
      Only 24.5 % of the children were reported to have completed the immunisation
      schedule. Fifty five (34.2%) of the 161 children were reported to have been ill
      in the preceding period of one month, the leading symptoms being fever (14.9%),
      cough (10.3%) and diarrhoea (3.9%). Forty six (28.6%) of the children were
      stunted, 34 (21.1%) underweight and 106 (65.8%) anaemic. CONCLUSION: The health
      status of children in institutionalised care is poor and needs better supervision
      and support to facilitate growth and wellbeing.

PMID- 24287747
TI  - Stroke recurrence in Nigerian children with sickle cell disease treated with
      hydroxyurea.
AB  - AIMS AND OBJECTIVES: To compare the outcome after a first clinical stroke,
      following treatment with and without hydroxyurea (HU). SUBJECTS AND METHODS: A
      retrospective review of a cohort of Nigerian children with SCD, who had suffered
      a first stroke, was carried out. Outcomes in the group of children who received
      and did not receive HU were compared. RESULTS: Thirty two children presented with
      stroke and one died of haemorrhagic stroke at presentation. All the children had
      haemoglobin SS phenotype, and ischaemic stroke was the predominant form seen.
      Mean age at first clinical stroke was 7 years, 7 months (SD=2 years, 4 months).
      Thirteen children received HU while 18 declined HU therapy. Maximum dose of HU
      ranged from 20-25 mg/kg/ day. The secondary stroke incidence of 7/100 person
      years in the HU group was significantly lower than the 28/100 person years in the
      non-HU group (P=0.001, OR 3.808, 95% CI 1.556, 9.317). Children who did not
      receive HU were more likely to drop out of school and to have moderate-severe
      motor disabilities requiring caregiver assistance for daily living. CONCLUSION:
      In settings where facilities for chronic blood transfusion are not accessible or
      feasible, HU therapy should be considered for secondary stroke prevention in
      children with SCD.

PMID- 24287748
TI  - Relationship between liver function tests and thyroid hormones in thyroid
      disorders.
AB  - AIMS AND OBJECTIVES: To evaluated the effect of thyroid dysfunction on liver
      function tests and if there is any correlation between them. MATERIALS AND
      METHODS: A total of 68 subjects (40 hyperthyroid and 28 hypothyroid) between the
      ages of 20-60 years old and 40 healthy euthyroid volunteers of the same age
      groups were studied. Plasma albumin, bilirubin (total and conjugated), thyroxine
      (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH); activities of
      aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase
      (ALP) and gamma glutamyltransferase (GGT) were estimated in the plasma of the
      participants. RESULTS: Plasma concentration of Total .bilirubin and liver enzyme
      activities increased significantly in both hyperthyroid and hypothyroid subjects.
      The positive correlations between thyroid hormones and liver enzymes in
      hyperthyroid subjects were negative in hypothyroid subjects and vice-visa.
      CONCLUSION: It can be concluded that both hyperthyroidism and hypothyroidism
      altered liver function tests. It is thus recommended that liver function tests
      interpretation in thyroid dysfunction should be with caution.

PMID- 24287749
TI  - Prostatic tumours among Nigerian males: a private practice experience in Benin
      City, South-South, Nigeria.
AB  - AIMS AND OBJECTIVES: To highlight the frequency and histological types of
      prostatic tumours seen in a private practice setting in Benin-City, South-South
      Nigeria. MATERIALS AND METHODS: Haematoxylin and eosin stained-slides of
      prostatic biopsies diagnosed at the Ashamas Foundation Diagnostic Centre, Benin
      City for 10 years were archived and studied. Histological request forms were
      analysed for clinical bio-data, type of biopsies and diagnosis. RESULTS: A total
      of 908 prostatic tumours comprising of 468 open prostatectomies, 378
      transurethral prostatectomies, 60 needle biopsies and 2 unspecified biopsy types
      were diagnosed. The peak age incidence of prostatic tumours was 60-69 years
      accounting for 37% of all prostatic tumours. Nodular prostatic hyperplasia (NPH)
      was the most common tumour accounting for 74.9%. Prostatic cancer was the second
      most common tumour accounting for 22.1% of all prostatic tumours. Six cases
      (1.3%) of incidental carcinoma were diagnosed out of the 680 cases of NPH.
      Transitional cell carcinoma and metastatic carcinoma constituted 0.2%, 0.1% of
      prostatic tumours respectively. In all, carcinosarcoma and fibrosarcoma accounted
      for 0.1% each of the prostatic tumours. High grade prostatic intraepithelial
      neoplasm accounted for 0.2% while 1.1% was inadequate for histopathological
      diagnosis. CONCLUSION: Nodular prostatic hyperplasia accounted for vast majority
      of all prostatic tumours in this study. However a significant percentage of
      prostatic adenocarcinoma was also encountered. Health education and population
      based screening modalities are advocated to reduce prostatic tumour morbidity and
      mortality in the Nigerian adult male population.

PMID- 24287750
TI  - Torsion of the testis and factors that determine the choice of orchidectomy and
      unilateral orchidopexy.
AB  - AIMS AND OBJECTIVES: To determine the age group affected by testicular torsion
      and the relationship with orchidectomy and unilateral orchidopexy. To determine
      if seasonal variation affects the incidence of torsion of the testis. MATERIALS
      AND METHODS: Data of confirmed patients with testicular torsion from July 1998 to
      June 2010 were retrieved. They were divided into two, group I (age<21 years) and
      group II (age e"21 years). The indices analyzed were the relationship of age
      group, occupation on orchidectomy and unilateral orchidopexy and seasonal
      variation and torsion. Cases of acute epididymo-orchitis, torsion of appendix
      testis, and testicular tumor were excluded from the study. RESULTS: A total of
      169 confirmed cases of testicular torsion were analysed.The estimated incidence
      was 12.1 cases per 100,000 populations. Their age range from 9 months to 45 years
      and mean age 23.8+/-7.6 (SD). 62.1% of torsion occurred at e" 21 years. One
      hundred and twenty patients (71%) had bilateral orchidopexy, 32 (18.9%) had
      orchidectomy and 17 (10.1%) had unilateral orchidopexy. In group II; unilateral
      orchidopexy was significant (p<0.03) and there was a correlation between the
      occupation and orchidectomy (p<0.02). There was no statistical correlation
      between total torsion and humidity (r=0.321, p=0.309), or ambient temperature
      (r=0.248, p=0.437). CONCLUSIONS: Testicular torsion was commoner in men age e" 21
      years and more students lost their testes. Unilateral orchidopexy should be
      considered in some cases. There was no relationship between torsion,
      orchidectomy, ambient temperature and relative humidity. The need for rigorous
      pre-school and pre-employment health education is advocated.

PMID- 24287751
TI  - Initial experience with spinal stabilisation with pedicle screws and rods in
      Nigerians: indications and outcome of surgery.
AB  - AIMS AND OBJECTIVES: To provide an initial experience in performing the procedure
      of the use of pedicle screws and rods for stabilisation of the spinal column in
      Nigerians with highlights on indications and outcome of surgery. MATERIALS AND
      METHODS: The hospital records of all the patients who had the procedure were
      retrieved. Biodata, presentation, neuroimaging findings, surgical procedure and
      postoperative outcome were extracted from records. Evidence of recurrent spinal
      instability, change in neurological status, wound infection and implant related
      complications postoperatively were used as outcome measures. RESULTS: Twenty
      seven procedures were performed in 26 patients [male: female was 1:1]. The age
      range was 26 to 77 years (mean=52.9, SD=13.7). Seventeen (65.4%) patients had
      degenerative spinal disease, while 9 (34.6%) had trauma. Five patients (19.2%)
      had thoracic spinal lesions and these were secondary to trauma, while there were
      21 (80.8%) patients with lumbar spinal lesions. The indications for surgery were
      spinal instability in trauma cases and/or anticipated instability for
      degenerative cases. Two spinal segments were fused during 11 (40.7%) procedures,
      3 in 10 (37.4%), 4 in 4 (14.8%) and 5 segments in 2 (7.4%) procedures. Post
      operatively, the Frankel grading improved in 6 (23.1%) patients, while it
      remained the same in 20 (76.9%). Back pain resolved in all but 1 (96.2%) patient.
      One (3.9%) patient each had screw fracture, recurrent instability and symptomatic
      redundant rod length while 2 (7.7%) peri-operative mortalities occurred due to
      cardiac events. CONCLUSION: The most common indication for posterior spinal
      stabilisation with pedicle screws and rods in this study is established or
      anticipated instability from degenerative lumbar spinal disease.Immediate
      stabilisation was achieved in majority of the patients without postoperative
      neurological deterioration.

PMID- 24287752
TI  - Late life depression among elderly hypertensive patients.
AB  - AIMS AND OBJECTIVES: To determine the correlates of late life depression among
      elderly hypertensive patients as seen in Zaria Northern Nigeria. SUBJECTS AND
      METHODS: Elderly hypertensive patients attending the cardiac clinic of Ahmadu
      Bello University Teaching Hospital Zaria were recruited for the study. They were
      interviewed using socio-demographic Questionnaire, Consortium to Establish
      Registry for Alzheimer's Disease (CERAD), Geriatric Depression Scale-30 and Stick
      Design Test. Patients that had a score of 11 and above in the GDS-30 were further
      interviewed using the Geriatric Mental State Schedule (GMSS) AGECAT. Data
      obtained from the study was analyzed using Statistical Package for Social
      Sciences windows version 15. All tests of significance were carried out at 5%
      level of probability. RESULTS: A total of 179 patients participated in the study
      out of which 110 (65.1%) were females. The mean age of the subject was 68.23+/
      5.72 years. The rate of late life depression based on International
      Classification of Diseases (ICD), 10th edition and Geriatric Mental State
      Schedule AGECAT (GMSS-AGECAT) diagnoses were 17. 88% (32) and 20.11 % (36)
      respectively. There was very good agreement between diagnoses based on ICD-10
      criteria and GMSS-AGECAT (kappa=0.82, p<.001). Late life depression was
      significantly associated with recent bereavement (OR=11.04, p=.001), poverty
      (OR=4.39, p=.036) and lower diastolic blood pressure (7.04, p=.008). CONCLUSION:
      The rate of late life depression in this study is comparable to that of other
      studies reported in the literature. Poverty and bereavement but not high blood
      pressure, are important factors associated with depression in the elderly.

PMID- 24287753
TI  - Clinical correlates of women requesting labour epidural analgesia in a tertiary
      hospital in Nigeria.
AB  - OBJECTIVES: To evaluate the clinical correlates of women who received pain relief
      in labour with lumbar epidural analgesia and also investigate the labour outcome.
      MATERIALS AND METHODS: A hospital -based case-control study conducted in a
      tertiary care facility in Nigeria. The clinical characteristics and delivery
      outcome of women who had epidural analgesia in labour were compared to those
      without. RESULTS: The utilisation rate of labour epidural analgesia during the
      study period was 13/1000 women. Tertiary education was significantly higher among
      women who had epidural analgesia in labour (22.7% vs 3.4%, p=0.0009). There were
      no statistically significant differences between women who had labour epidural
      analgesia and the controls in terms of labour and delivery by caesarean section.
      The second stage of labour was prolonged in women who received epidural for pain
      relief in labour (p=0.005). The neonatal indices (Mean birth weight or Apgar
      score<7 in first minute) were similar. CONCLUSION: This study suggests that
      labour epidural analgesia is not associated with increased caesarean section and
      adverse foetal outcome. This is of value in increasing the acceptance of this
      service by pregnant women in Nigeria.

PMID- 24287754
TI  - Cost of epilepsy care in a Nigerian tertiary hospital.
AB  - AIMS AND OBJECTIVES: The economic impact of epilepsy is enormous in terms of use
      of health care resources and loss of productivity. There is presently scanty data
      on economic impact of epilepsy in Nigeria,which necessitated this study. SUBJECTS
      AND METHODS: This cross-sectional study is on epilepsy patients age e"16 years
      who attended Neurology clinic at UITH Ilorin. Data collected included clinical
      characteristics, utilisation of resources and cost of care. Direct medical costs
      included recurring costs like consultation, hospitalisation, medication and
      investigation fees. Indirect costs were number of days lost due to seizure attack
      and travelling to clinic by patients and relatives. RESULTS: Sixty-five patients
      (32 males, 33 females) participated in the study with age range of 16 to 74 years
      and mean (SD) of 35+/-17 years. Total clinic attendance was 314 days and 53 days
      were spent on admission. Close to 25% of patients resided outside Ilorin
      metropolis and distance traveled to attend clinic varied from 4 to 200 km
      (mean=47+/-30.6 km). The total annual cost per patient was 41, 878 ($279.2 USD).
      It consisted of direct cost [DC] of 33,616 (80%) and indirect cost [IC] of 8262
      (20%). The three leading consumptive items in DC were: antiepileptic drugs (AEDs)
      24,138, investigations-5373 and transportation-2387. Majority (76.9%) of the
      patients were on carbamazepine. Self-estimated monthly family income varies from
      3000 to 200,000 (median of 25,000). Only 23 patients (35.4%) bore the cost of
      care themselves. Of the IC, lost earnings due to absenteeism from work amounted
      to 6177. Equivalent of 1 USD was 150 at time of study. CONCLUSION: AEDs accounted
      for a significant proportion of TC. Increase in availability of generic drugs
      could help bring down the cost of care within affordable reach of indigent
      patients.

PMID- 24287755
TI  - Perioperative considerations in orthopaedic patients with diabetes mellitus: a
      review.
AB  - Patients with diabetes mellitus are predisposed to a host of orthopaedic problems
      which may require surgery and many patients with orthopaedic conditions may have
      unrecognised hyperglycaemia presenting for the first time at surgery. This group
      of patients are also prone to adverse surgical outcomes like post-operative
      infections and poor wound healing. The control of hyperglycaemia in orthopaedic
      patients with diabetes mellitus is the key in optimising surgical outcome in
      these patients. Peri-operative insulin is the main antihyperglycaemic agent of
      use. The risk of hypoglycaemia with tighter peri-operative glucose control
      outweighs its potential benefits. Blood glucose control with insulin infusion is
      better than sliding scale insulin. Control of infections and promotion of wound
      healing are necessary adjuncts in the management to optimise surgical outcome. 

PMID- 24287756
TI  - Fatal haemorrhage from an ultrasound guided fine needle aspiration of the liver
      in a patient with primary hepatocellular carcinoma: case report.
AB  - A case of fatal haemorrhage is reported among 72 ultrasound (US) guided
      percutaneous fine-needle aspiration liver biopsies (FNAB) performed in the gastro
      intestinal unit of Medicine Department in a tertiary hospital. The patient had
      primary hepatocellular carcinoma (PHCC) with advanced hepatic cirrhosis. Death
      was due to bleeding from liver nodule resulting in intra-peritoneal haemorrhage.
      Pre-procedure laboratory tests did not reveal the existence of major bleeding
      disorders in the patient. This event is our first experience, but colour flow
      Doppler ultrasound guidance has been reported to prevent its occurrence. The use
      of FNAB for the diagnosis of PHCC should therefore be guided with colour flow
      Doppler ultrasound scan to prevent haemorrhage. In addition, there should be
      proper selection of patients for FNAB especially in areas where there are no
      colour flow Doppler ultrasound scans. 

PMID- 24287757
TI  - Natal tooth and cultural impact on its management in a tropical neonatal unit: a
      case report.
AB  - The incidence of natal tooth is uncommon and its management could be fraught with
      challenges. A 3 day old female presented with features of sepsis and a natal
      tooth. Treatment for sepsis was permitted and successfully instituted but
      definitive management of the natal tooth was deferred, for cultural reasons, by
      the parents. The case documents the occurrence of natal tooth and highlights the
      impact of cultural beliefs on management of some medical conditions. It
      underscores the need to develop the relationship between orthodox medical care
      and cultural beliefs, in susceptible communities, with a view to achieving
      optimal health care delivery. 

PMID- 24287758
TI  - H-type tracheo-oesophageal fistula: a diagnostic challenge in a resource-poor
      country. A case report.
AB  - H-type fistula is a rare form of congenital tracheo-oesophageal fistula
      accounting for 4% of all cases of Tracheo-oesophageal fistula. The typical
      picture is that of recurrent chest infection due to both missed and delayed
      diagnosis as well as cyanosis and choking during feeds. In resource poor
      countries this problem is further exaggerated by ignorance, poverty and lack of
      access to basic investigative modalities. This is the case of [abstract
      incomplete].

PMID- 24287759
TI  - Congenital long-QT syndrome in a Nigerian child: a case report.
AB  - CASE REPORT: We describe the clinical manifestation and the challenges of
      diagnosing Long QT syndrome, type 1 (LQTS1), in an 8-year old girl who presented
      at the Paediatric Cardiology Clinic with syncopal attacks following dancing and
      excitement. Her initial ECG showed normal QT interval of 380msec (QTc=440 msec),
      but later, increased to 410 msec (QTc=520 msec) following epinephrine challenge
      test. CONCLUSION: The challenges with the diagnosis of LQTS1 in children in
      resource-constrained setting and the need for vigilance in children with syncopal
      attacks and other cardiac events with normal QT intervals on an electrocardiogram
      are thus highlighted.

PMID- 24287760
TI  - Angiomyolipoma presenting as renal abscesses: a consideration for further
      evaluation of renal abscess.
AB  - AIMS AND OBJECTIVES: This is to describe an usual presentation of renal
      angiomyolipoma as renal abscess CASE REPORT: This is a case report of a 51 year
      old man with clinical and radiological features suggestive of renal abscess. The
      patient had exploratory laparatomy and a simple nephrectomy for a non functioning
      kidney which was more like a bag of pus. The histological report however revealed
      renal abscess coexisting with angiomyolipoma supporting previous reports that
      renal abscess may be a harbinger of other renal pathologies. CONCLUSION:
      Abscesses are usually managed by drainage and the dictum of 'wherever there is
      pus let it out' holds generally but this does not always suffice in renal
      abscesses because renal abscesses are often found in the background of other
      diseases which may be of more clinical importance.

PMID- 24287761
TI  - Oxidative addition chemistry of tetrathiocines: synthesis, structures and
      properties of group 10 dithiolate complexes.
AB  - Oxidative addition of the electron-rich tetra-methoxy-dibenzo-1,2,5,6
      tetrathiocine [(MeO)2C6H2S2]2 to zero-valent group 10 transition metal complexes
      in the presence of diphenylphosphinoethane (dppe) affords the corresponding
      dithiolate complexes, [(DMOBD)M(dppe)] (DMOBD = dimethoxybenzenedithiolato,
      (MeO)2C6H2S2(2-); M = Ni, Pd, Pt) in high yield which were characterized by
      single crystal X-ray diffraction. Whereas the Pd and Pt complexes exhibit two
      quasi-reversible 1e(-) oxidation processes, the nickel species undergoes a quasi
      reversible 1e(-) reduction. 

PMID- 24287762
TI  - Right ventricular strain as a novel approach to analyze right ventricular
      performance in patients with heart failure.
AB  - Speckle tracking echocardiography (STE) has recently applied as imaging technique
      to accurately evaluate right ventricular (RV) function. STE provides a non
      Doppler, angle-independent and objective quantification of RV myocardial
      deformation. Data regarding feasibility, accuracy and clinical applications of RV
      strain are rapidly gathering, especially in the setting of heart failure
      patients. This review describes the fundamental concepts of RV-STE and discusses
      its emerging clinical applications, focusing on the useful of this technique in
      the clinical management of patients with advanced heart failure. 

PMID- 24287763
TI  - Special issue of photosynthetic research.
AB  - This Special Issue of Photosynthesis Research honors Louis M. N. Duysens,
      Roderick K. Clayton, and George Feher, three pioneering researchers whose work on
      bacterial photosynthesis laid much of the groundwork for our understanding of the
      role of the reaction center in photosynthetic light energy conversion. Their key
      discoveries are briefly summarized and an overview of the special issue is
      presented.

PMID- 24287764
TI  - Drugging cancer genomes.

PMID- 24287765
TI  - Learning from the 2012-2013 class of breakthrough therapies.

PMID- 24287766
TI  - The GHIT fund shows its cards.

PMID- 24287770
TI  - Market watch: defining and quantifying the use of personalized medicines.

PMID- 24287771
TI  - Trial watch: phase II boost for glutamate-targeted antidepressants.

PMID- 24287772
TI  - NIH denies march-in rights on Norvir patent.

PMID- 24287774
TI  - Charles Hugh-Jones. Interview by Asher Mullard.

PMID- 24287775
TI  - Bone disorders: targeting NOX4 knocks down osteoporosis.

PMID- 24287779
TI  - Neurological disorders: Chloride extrusion alleviates neuropathic pain.

PMID- 24287783
TI  - Mutually ordered self-assembly of discotic liquid crystal-graphene
      nanocomposites.
AB  - The room temperature anthraquinone discotic 1,5-dihydroxy-2,3,6,7-tetrakis(3,7
      dimethyloctyloxy)-9,10-anthraquinone (RTAQ) self-assembles in the presence of
      octadecylamine functionalized graphene (f-graphene) into an ordered sandwich like
      structure, where the discotic molecules form columnar structures on graphene
      sheets. Cryo-SEM and SEM images provide evidence for this ordering. This
      behaviour is also supported by polarizing optical microscopy, differential
      scanning calorimetry, X-ray diffraction and conductivity studies of
      nanocomposites. 

PMID- 24287784
TI  - Prediction of dopant atom distribution on nanocrystals using thermodynamic
      arguments.
AB  - A theoretical approach aiming at the prediction of segregation of dopant atoms on
      nanocrystalline systems is discussed here. It considers the free energy
      minimization argument in order to provide the most likely dopant distribution as
      a function of the total doping level. For this, it requires as input (i) a fixed
      polyhedral geometry with defined facets, and (ii) a set of functions that
      describe the surface energy as a function of dopant content for different
      crystallographic planes. Two Sb-doped SnO2 nanocrystalline systems with different
      morphology and dopant content were selected as a case study, and the calculation
      of the dopant distributions expected for them is presented in detail. The
      obtained results were compared to previously reported characterization of this
      system by a combination of HRTEM and surface energy calculations, and both
      methods are shown to be equivalent. Considering its application pre-requisites,
      the present theoretical approach can provide a first estimation of doping atom
      distribution for a wide range of nanocrystalline systems. We expect that its use
      will support the reduction of experimental effort for the characterization of
      doped nanocrystals, and also provide a solution to the characterization of
      systems where even state-of-art analytical techniques are limited. 

PMID- 24287782
TI  - Chemical predictive modelling to improve compound quality.
AB  - The 'quality' of small-molecule drug candidates, encompassing aspects including
      their potency, selectivity and ADMET (absorption, distribution, metabolism,
      excretion and toxicity) characteristics, is a key factor influencing the chances
      of success in clinical trials. Importantly, such characteristics are under the
      control of chemists during the identification and optimization of lead compounds.
      Here, we discuss the application of computational methods, particularly
      quantitative structure-activity relationships (QSARs), in guiding the selection
      of higher-quality drug candidates, as well as cultural factors that may have
      affected their use and impact. 

PMID- 24287785
TI  - Photon buildup factors in some dosimetric materials for heterogeneous radiation
      sources.
AB  - Effective photon energy absorption (EABF(eff)) and exposure buildup factors
      (EBF(eff)) have been calculated based on the effective energy concept, for some
      dosimetric materials such as water, polymethyl methacrylate (PMMA), polystyrene,
      solid water (WT1), RW3 (Goettingen Water 3), and ABS (acrylonitrile butadiene
      styrene), for MV X-rays and (60)Co gamma rays. Firstly, the equivalent atomic
      numbers (Z(eq)) of the given materials have been determined using the effective
      photon energies (E eff). Then, the five-parameter geometric progression (G-P)
      fitting approximation has been used to calculate both EABF(eff) and EBF(eff)
      values. Since the G-P fitting parameters are not available for the E eff values
      of the given materials, a linear interpolation in which a function of the
      logarithm of the variable is used has been performed, in order to calculate the
      parameters in each E eff, which will be further used for the determination of
      EABF(eff) and EBF(eff). In the present paper, water equivalence properties of the
      given materials are also discussed based on the effective buildup factors. In
      this study, special emphasis is placed on the calculation of EABF(eff) and
      EBF(eff) values of different materials for photons that are not monoenergetic but
      heterogeneous in energy, to obtain an initial and prior knowledge of the probable
      energy and buildup of photons at locations of interest, i.e., to understand
      whether the real absorbed dose occurs at the surface or somewhere inside the
      medium of interest.

PMID- 24287781
TI  - Modulation of oxidative stress as an anticancer strategy.
AB  - The regulation of oxidative stress is an important factor in both tumour
      development and responses to anticancer therapies. Many signalling pathways that
      are linked to tumorigenesis can also regulate the metabolism of reactive oxygen
      species (ROS) through direct or indirect mechanisms. High ROS levels are
      generally detrimental to cells, and the redox status of cancer cells usually
      differs from that of normal cells. Because of metabolic and signalling
      aberrations, cancer cells exhibit elevated ROS levels. The observation that this
      is balanced by an increased antioxidant capacity suggests that high ROS levels
      may constitute a barrier to tumorigenesis. However, ROS can also promote tumour
      formation by inducing DNA mutations and pro-oncogenic signalling pathways. These
      contradictory effects have important implications for potential anticancer
      strategies that aim to modulate levels of ROS. In this Review, we address the
      controversial role of ROS in tumour development and in responses to anticancer
      therapies, and elaborate on the idea that targeting the antioxidant capacity of
      tumour cells can have a positive therapeutic impact. 

PMID- 24287786
TI  - HIV prevalence, substance use, and sexual risk behaviors among transgender women
      recruited through outreach.
AB  - Transgender women ("transwomen") face a disproportionate HIV disease burden; the
      odds of being HIV-positive are estimated to be 34.2 times higher for transwomen
      than the United States adult population. From January 1, 2005 through December
      31, 2011, HIV prevention outreach encounters were conducted with 2,136 unique
      transwomen on the streets and at high-risk venues in Los Angeles County. The
      outreach encounters were comprised of a low-intensity health education and risk
      reduction intervention, which included referrals to needed services. The goal of
      the encounters was to assess the participant's level of substance use and sexual
      risk behaviors to provide appropriate risk reduction strategies and supplies. The
      sample evidenced high rates of recent alcohol (57.7 %), marijuana (25.6 %), and
      methamphetamine (21.5 %) use, lifetime injection drug or illegal hormone use
      (66.3 %), and recent engagement in sex work (73.3 %). Multivariate logistic
      regression analysis revealed that recent methamphetamine (AOR = 2.09; p <= 0.001)
      and/or crack cocaine (AOR = 2.19; p = 0.010) use, injection drug/hormone use (AOR
      = 1.65; p <= 0.001), unprotected anal intercourse during sex work (AOR = 2.24; p
      = 0.029), and any non-Hispanic minority racial status were all associated with
      increased odds of reporting a HIV-positive status. The transwomen encountered via
      outreach exhibited many risk co-factors for HIV infection and transmission.

PMID- 24287787
TI  - Current cigarette smoking among HIV-positive current and former drug users:
      associations with individual and social characteristics.
AB  - Cigarette smoking is endemic among HIV-positive populations and is related to
      substantial morbidity and mortality. Research has largely focused on individual
      level characteristics associated with smoking, with less attention to social
      factors. We aimed to explore individual- and social-level characteristics
      associated with current cigarette smoking among people living with HIV. Data came
      from 358 individuals on antiretroviral therapy interviewed in a study on informal
      HIV caregiving, conducted in Baltimore, MD, USA. Most participants (75 %) were
      current smokers and 45 % reported current illegal drug use. In adjusted logistic
      regression analyses, current drug use (aOR 2.90, 95 % CI 1.58-5.30), 12-step
      program participation (aOR 1.74, 95 % CI 1.02-2.97), and having a main Supporter
      who is a current smoker (aOR 1.93, 95 % CI 1.12-3.33) were associated with
      current smoking. Findings suggest the importance of social-level factors in
      cigarette smoking among HIV seropositive drug users and have implications for
      developing targeted smoking cessation interventions for smokers living with HIV.

PMID- 24287788
TI  - Implications of adiponectin in linking metabolism to testicular function.
AB  - Obesity is a major health problem, contributing to the development of various
      diseases with aging. In humans, obesity has been associated with reduced
      testosterone production and subfertility. Adipose tissue is an important source
      of hormones having influences on both metabolism and reproduction. Among them,
      the production and secretion of adiponectin is inversely correlated to the
      severity of obesity. The purpose of this review of literature is to present the
      current state of knowledge on adiponectin research to determine whether this
      hormone affects reproduction in men. Surprisingly, evidences show negative
      influences of adiponectin on GnRH secretion from the hypothalamus, LH and FSH
      secretion from the pituitary and testosterone at the testicular level. Thus far,
      the involvement of adiponectin in the influence of metabolism on reproduction in
      men is limited. However, adiponectin and its receptors are expressed by different
      cell types of the male gonad, including Leydig cells, spermatozoa, and
      epididymis. In addition, actions of adiponectin at the testicular level have been
      shown to promote spermatogenesis and sperm maturation. Therefore,
      autocrine/paracrine actions of adiponectin in the testis may contribute to
      support male reproductive function. 

PMID- 24287789
TI  - Interleukin-21 is associated with disease activity in patients with Graves'
      disease.
AB  - Graves' disease (GD) is a common autoimmune disease mainly caused by thyroid
      stimulating antibodies (TSAbs). Interleukin 21 (IL-21) has recently been reported
      to play a vital role in the production of pathogenic autoantibodies in several
      autoimmune diseases, but less is known about GD. This study aimed to investigate
      the serum levels of IL-21 in GD patients and to explore their association with
      disease activity. We performed a case-control association study of 152 patients
      with GD and 32 healthy controls. All patients were further classified into three
      subgroups: the GD-untreated group (n = 70), the GD-recurrence group (n = 41), and
      the GD-remission group (n = 41). Serum IL-21 levels were assayed with ELISA. TSAb
      activity was measured by an in vitro bioassay. Changes in serum IL-21 were also
      observed in 12 GD patients before and after treatment. Additionally, correlations
      among the serum IL-21 and free triiodothyronine (FT3), free thyroxine (FT4),
      thyrotropin (TSH), thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies
      (TGAb), thyrotropin receptor antibody (TRAb), and TSAb were also analyzed. The
      serum IL-21 levels in all GD patients were significantly higher than those in the
      control group (P < 0.001), and specifically, both the GD-untreated and GD
      recurrence groups had elevated serum IL-21 compared to the control group (P <
      0.001). Moreover, serum IL-21 in newly diagnosed patients markedly decreased
      after treatment (P < 0.001). Additionally, the serum IL-21 levels in GD-goiter
      patients were higher than those of the GD-non-goiter patients (P < 0.001).
      However, no significant differences were found in the serum IL-21 levels in
      patients with or without Graves' ophthalmopathy. Importantly, serum IL-21
      positively correlated with FT3, FT4, TPOAb, TGAb, and TRAb (r = 0.5053, r =
      0.3266, r = 0.1792, r = 0.2445, and r = 0.4096, respectively; all P < 0.0001),
      and particularly with TSAb activity (r = 0.8171, P < 0.0001), negatively
      correlated with TSH (r = -0.2713, P < 0.0001). Serum IL-21 levels were
      significantly elevated in patients with GD and decreased after treatment;
      moreover, IL-21 may be associated with the clinical disease activity. These
      observations suggest that IL-21 may play an important role in the pathogenesis of
      GD.

PMID- 24287790
TI  - Association between leisure time physical activity and metabolic syndrome: a meta
      analysis of prospective cohort studies.
AB  - A great number of prospective studies have investigated the relationship between
      leisure time physical activity (LTPA) and metabolic syndrome (MetS) risk.
      However, the results have been inconsistent. The aim of this study was to clarify
      the relationship between LTPA and MetS risk. Literature databases were searched
      including PubMed and Embase up to June 2013. A total of 17 studies, including
      64,353 participants and 11,271 incident cases, were included in the meta
      analysis. A high level of LTPA was statistically associated with decreased risk
      of MetS [high vs. low: relative risk (RR) = 0.80, 95 % confidence interval (CI)
      0.75-0.85], whereas a moderate level of LTPA was weakly associated with decreased
      risk of MetS (moderate vs. low: RR = 0.95, 95 % CI 0.91-1.00). Subgroup analyses
      indicated that the association between a moderate level of LTPA and decreased
      risk of MetS was only significant in men (moderate vs. low: RR = 0.88, 95 % CI
      0.81-0.97) and in studies with more than a 10-year follow-up period (moderate vs.
      low: RR = 0.90, 95 % CI 0.84-0.97). A high level of LTPA was statistically
      associated with decreased risk of MetS in each subgroup. A higher level of LTPA
      is associated with a lower risk of MetS. These findings could have public health
      implications with regard to prevention of MetS through lifestyle interventions.

PMID- 24287791
TI  - Transcription factor Ets-1 inhibits glucose-stimulated insulin secretion of
      pancreatic beta-cells partly through up-regulation of COX-2 gene expression.
AB  - Increased cyclooxygenase-2 (COX-2) expression is associated with pancreatic beta
      cell dysfunction. We previously demonstrated that the transcription factor Ets-1
      significantly up-regulated COX-2 gene promoter activity. In this report, we used
      the pancreatic beta-cell line INS-1 and isolated rat islets to investigate
      whether Ets-1 could induce beta-cell dysfunction through up-regulating COX-2 gene
      expression. We investigated the effects of ETS-1 overexpression and the effects
      of ETS-1 RNA interference on endogenous COX-2 expression in INS-1 cells. We used
      site-directed mutagenesis and a dual luciferase reporter assay to study putative
      Ets-1 binding sites in the COX-2 promoter. The effect of ETS-1 1 overexpression
      on the insulin secretion function of INS-1 cells and rat islets and the potential
      reversal of these effects by a COX-2 inhibitor were determined in a glucose
      stimulated insulin secretion (GSIS) assay. ETS-1 overexpression significantly
      induces endogenous COX-2 expression, but ETS-1 RNA interference has no effect on
      basal COX-2 expression in INS-1 cells. Ets-1 protein significantly increases COX
      2 promoter activity through the binding site located in the -195/-186 region of
      the COX-2 promoter. ETS-1 overexpression significantly inhibited the GSIS
      function of INS-1 cells and islet cells and COX-2 inhibitor treatment partly
      reversed this effect. These findings indicated that ETS-1 overexpression induces
      beta-cell dysfunction partly through up-regulation of COX-2 gene expression.
      Moreover, Ets-1, the transcriptional regulator of COX-2 expression, may be a
      potential target for the prevention of beta-cell dysfunction mediated by COX-2. 

PMID- 24287792
TI  - Role of core needle biopsy for patients with indeterminate, fine-needle
      aspiration cytology.

PMID- 24287793
TI  - Extract of Litsea japonica ameliorates blood-retinal barrier breakdown in db/db
      mice.
AB  - Loss of blood-retinal barrier (BRB) properties is an important feature in the
      pathology of diabetic retinopathy. Endothelium integrity is important for the
      normal vascular function. Litsea japonica (Thunb.) Jussieu is a Korean native
      plant that is consumed as a vegetable food. In this study, we evaluated the
      ability of an ethanol extract of L. japonica to prevent retinal vascular leakages
      in db/db mice, which is an animal model of type II diabetes. L. japonica extracts
      (LJE, 100 and 250 mg/kg) were administered once a day, orally, for 12 weeks.
      Vehicle-treated db/db mice exhibited hyperglycemia and retinal vascular leakage.
      LJE treatment blocked diabetes-induced BRB breakdown and decreased retinal VEGF
      expression in db/db mice. LJE also inhibited the degradation of occludin, which
      is an important tight junction protein. These findings support the potential
      therapeutic usefulness of L. japonica for retinal vascular permeability diseases.

PMID- 24287794
TI  - Non-alcoholic fatty liver disease: a diabetologist's perspective.
AB  - In the recent years, non-alcoholic fatty liver disease (NAFLD) has emerged as the
      commonest cause of chronic liver disease in the developed world. The global
      epidemic of obesity secondary to physical inactivity and adverse food habits
      accounts for the alarming rise in NAFLD. Metabolic syndrome plays a major role in
      the pathogenesis of both NAFLD and type 2 diabetes mellitus (T2DM). Whilst most
      cases of NAFLD remain asymptomatic with only hepatic steatosis, about 30 %
      progress to non-alcoholic steatohepatitis with chronic liver inflammation that
      can lead on to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma.
      Because of the similar pathogenesis shared between T2DM and NAFLD, T2DM occurs as
      an important complication in many cases of NAFLD, and many cases of T2DM are
      further complicated by NAFLD. Rapid progression and increased complications of
      the individual diseases is the end result of this dual coexistence. Diagnosis of
      NAFLD relies upon hepatic imaging, serum biochemical markers, and liver biopsy.
      As in T2DM, the most important management option for patients with NAFLD is
      lifestyle changes targeted at weight reduction. Other treatment options include
      insulin sensitizers (metformin and pioglitazone), vitamin E, incretin mimetics,
      omega-3 fatty acids, cholesterol lowering agents, orlistat, and bariatric
      surgery. The clinical spectrum, patho-physiological features and therapeutic
      options of NAFLD share many things in common with T2DM and therefore, this review
      is to highlight the diabetologist's perspective of the disease.

PMID- 24287795
TI  - Common genetic variation in sFRP5 is associated with fat distribution in men.
AB  - Considering the role of sFRP5 in Wnt signalling, an important group of pathways
      regulating adipogenesis and inflammation, we performed a genetic association
      study on sFRP5 polymorphisms in a population of obese and lean individuals. Using
      information from the HapMap, two tagSNPs were identified in the sFRP5 gene region
      and genotyped on a population of 1,014 obese, non-diabetic individuals and 606
      lean controls. We performed logistic and linear regression analysis including a
      wide variety of obesity parameters (BMI, waist circumference, height, WHR, fat
      mass, fat mass percentage and visceral, subcutaneous and total abdominal fat), in
      addition to OGTT and HOMA-IR values. We were able to show a significant
      association of sFRP5 with both total abdominal and subcutaneous fat. The
      association signal was only seen in obese males, and in this population, the
      minor allele of rs7072751 explains 1.8 % of variance in total abdominal fat. In
      addition, we saw a trend towards an association of rs10748709 with glucose
      metabolism. Although further research is necessary, we can conclude that sFRP5 is
      a significant regulator of fat development and distribution in obese males. We
      postulate that altered transcription factor binding on the rs7072751 surrounding
      sequence might play a role in the associations we found with both total abdominal
      and subcutaneous fat. In addition, although no conclusive evidence was found, our
      results indicate that sFRP5 genetic variation may affect glucose metabolism and
      it would be interesting to investigate this further.

PMID- 24287796
TI  - Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and
      their correlation to different clinical forms.
AB  - Cardiometabolic disorders have been associated with primary hyperparathyroidism
      (PHPT), while the relationship of cardiovascular risk score (CRS) and metabolic
      syndrome (MS) with different clinical presentation of PHPT remains undefined. Our
      aim was to evaluate CRS, MS and its components in PHPT looking for their
      correlation to different clinical forms. In 68 consecutive PHPT patients and 68
      matched controls, CRS, MS and its components were assessed to perform an
      observational case-control study at an ambulatory referral center for Bone
      Metabolism Diseases. Patients were stratified in symptomatic and asymptomatic
      PHPT; these latter were divided in high-risk and low-risk subgroups for end-organ
      damage. An increased proportion of PHPT patients had intermediate-high CRS and MS
      (mean, 95 % Confidence Interval (CI) 51.5 %, 39.6-63.3 and 20.6 %, 11.0-30.2,
      respectively, p < 0.02 vs. controls). Intermediate-high CRS was prevalent both in
      symptomatic and low-risk asymptomatic PHPT while MS resulted prevalent in low
      risk asymptomatic but not in symptomatic PHPT. Type 2 DM, IFG, mixed
      dyslipidemia, hypertriglyceridemia, HDL-hypocholesterolemia, and LDL
      hypercholesterolemia predominated in low-risk asymptomatic, while only LDL
      hypercholesterolemia prevailed also in symptomatic PHPT. In patients and controls
      without cardiometabolic risk factors, HOMA-IR index was significantly increased
      in PHPT vs. controls (p < 0.03) and associated to total calcium (R = 0.73; p <
      0.001). By multivariate analysis low-risk asymptomatic PHPT predicted MS after
      adjusting for age, sex, and BMI. Our data show an increased frequency of
      intermediate-high CRS both in symptomatic and low-risk asymptomatic PHPT while MS
      prevails in low-risk asymptomatic PHPT, supporting the potential for
      cardiovascular morbidity and mortality also in this form.

PMID- 24287797
TI  - Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.
AB  - As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors
      was tested for prolactinoma outcomes and therapy. The objective of this study was
      to characterize ErbB receptor expression in prolactinomas and then perform a
      pilot study treating resistant prolactinomas with a targeted tyrosine kinase
      inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for
      dopamine agonist resistant prolactinomas in tertiary referral center. We
      performed immunofluorescent staining of a tissue array of 29 resected
      prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical
      features. Two patients with aggressive resistant prolactinomas enrolled and
      completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor
      and hormone assessments. Main outcome measures were positive tumor staining of
      respective ErbB receptors, therapeutic reduction of prolactin levels and tumor
      shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects
      treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92
      %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3.
      Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03),
      suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01).
      Higher DA response rates were observed in tumors with higher ErbB3 expression.
      Prolactinoma expression of specific ErbB receptors is associated with tumor
      invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors
      may be effective therapy in patients with resistant prolactinomas.

PMID- 24287798
TI  - Changes of gastric aromatase and portal venous 17beta-estradiol during the
      postnatal development and estrus cycle in female rats.
AB  - Gastric parietal cells synthesize and secrete a large amount of 17beta-estradiol
      into the portal vein. However, there are few studies on the gastric 17beta
      estradiol during the postnatal development and estrus cycle. The purpose of this
      study is to clarify the onset and the prepubertal change of gastric 17beta
      estradiol synthesis; and the effect of gastric 17beta-estradiol on the estrus
      cycle. Wistar female rats aged from 15 to 40 days and 10 weeks were used in the
      study. The expression of aromatase and estrogen receptor (ER) alpha mRNAs and
      proteins was analyzed in the stomach, ovary, and liver by RT-PCR,
      immunohistochemistry, and Western blotting methods; and 17beta-estradiol levels
      in the artery and portal vein were assayed by the ELISA method. During postnatal
      development, aromatase protein and aromatase cells in gastric mucosa and portal
      venous 17beta-estradiol levels started increasing after 20 days, and then these
      subjects reached nearly the same levels as mature female rats at 40 days. In the
      estrus cycle, the arterial 17beta-estradiol level in proestrus was the highest,
      and the value was 60 % of the portal venous level. Gastric aromatase protein and
      portal venous 17beta-estradiol levels did not change during the estrus cycle.
      Ovarian ERalpha levels fluctuated in the same pattern of arterial 17beta
      estradiol; however, hepatic ERalpha levels went unchanged. These results showed
      that gastric aromatase in females expresses earlier than the sexual maturation,
      and the gastric aromatase protein reaches the same levels as mature rats at 40
      days. Furthermore, 17beta-estradiol synthesis and secretion in the stomach is not
      related to those in the ovary.

PMID- 24287799
TI  - Biochemical persistence in thyroid cancer: is there anything to worry about?
AB  - To evaluate the outcome of differentiated thyroid cancer (DTC) patients with
      biochemical persistence of disease (BP) after initial treatment (total
      thyroidectomy with or without lymph node dissection (LND) and thyroid remnant
      ablation). BP was defined as suppressed thyroglobulin (Tg) levels <1 ng/ml and
      rhTSH-stimulated thyroglobulin (St-Tg) >1ng/ml, with no evidence of structural
      disease. Structural persistence/recurrence (SPR): clinically identifiable
      disease. We reviewed 278 records of DTC patients. Tg-Ab positive patients (n =
      73) were excluded and 32 were included in the analysis (median age 45 years,
      range 18-77 years); risk of recurrence ATA was: low in 38 %, Intermediate in 47
      %, and high in 15 % of patients. All subjects had Tg levels <1 ng/ml under
      thyroid hormone therapy. Patients were divided into three groups: Group 1: St-Tg
      1-2 ng/ml, n = 6; Group 2: St-Tg 2-10 ng/ml, n = 17; Group 3: St-Tg > 10 ng/ml, n
      = 9. In 5/32 (16 %) patients, SPR was observed after a median follow-up of 6
      years (range 2-23 years). In Group 1: all patients were considered with no
      evidence of disease after a median follow-up of 2 years (range 1-2.5 years). In
      Group 2: 13/17 (76.5 %) patients continued with only a BP after a median follow
      up of 4 years (range 2-10 years) and 4/17 (23.5 %) patients with intermediate
      risk of recurrence had a structural persistence (lymph nodes metastasis)
      diagnosed between 1 and 3.5 years after initial assessment. Following LND, all of
      them remained with BP after a median of 2 years (range 1.5-5 years). In Group 3:
      8/9 (89 %) patients had BP after a median follow-up of 7 years (range 2-23 years)
      and 1/9 (11 %) had a SPR diagnosed 28 months after initial assessment, LND was
      indicated but he continued with BP, 5 years after the second surgery. Most
      patients with DTC and BP present an indolent course of the disease. In these
      patients the diagnosis of the structural recurrence did not change the outcome
      because all of them continued with BP.

PMID- 24287800
TI  - Protective effect of S-allyl-L-cysteine against endoplasmic reticulum stress
      induced neuronal death is mediated by inhibition of calpain.
AB  - Endoplasmic reticulum (ER) stress, implicated in various neurodegenerative
      processes, increases the level of intracellular Ca(2+) and leads to activation of
      calpain, a Ca(2+)-dependent cysteine protease. We have shown previously that S
      allyl-L-cysteine (SAC) in aged garlic extracts significantly protects cultured
      rat hippocampal neurons (HPNs) against ER stress-induced neurotoxicity. The
      neuroprotective effect of SAC was compared with those of the related antioxidant
      compounds, L-cysteine (CYS) and N-acetylcysteine (NAC), on calpain activity in
      HPNs and also in vitro. SAC, but not CYS or NAC, reversibly restored the survival
      of HPNs and increased the degradation of alpha-spectrin, a substrate for calpain,
      induced by tunicamycin, a typical ER stress inducer. Activities of MU- and m
      calpains in vitro were also concentration dependently suppressed by SAC, but not
      by CYS or NAC. At submaximal concentration, although ALLN (5 pM), which blocks
      the active site of calpain, and calpastatin (100 pM), an endogenous calpain
      inhibitor protein, additively inhibited MU-calpain activity in vitro in
      combination with SAC, the effect of PD150606 (25 MUM), which prevents interaction
      of Ca(2+) with the Ca(2+)-binding site of calpain, was unaffected by SAC. In
      contrast, SAC (1 mM) significantly reversed the effect of PD150606 at a
      concentration that elicited supramaximal inhibition (100 MUM), but did not affect
      ALLN (1 nM)- and calpastatin (100 nM)-induced inhibition of MU-calpain activity.
      These results suggest that the protective effects of SAC against ER stress
      induced neuronal cell death are not attributable to antioxidant activity, but to
      suppression of calpain through interaction with its Ca(2+)-binding site.

PMID- 24287801
TI  - Using the Theory of Planned Behavior to identify key beliefs underlying chlamydia
      testing intentions in a sample of young people living in deprived areas.
AB  - The Theory of Planned Behavior was used to identify the key behavioural,
      normative and control beliefs underlying intentions to test regularly for
      chlamydia among young people living in socially and economically deprived areas -
      a high-risk group for infection. Participants (N = 278, 53% male; mean age 17
      years) were recruited from a vocational college situated in an area in the most
      deprived national quintile (England). Participants completed measures of
      behavioural, normative and control beliefs, plus intention to test regularly for
      chlamydia. The behavioural, normative and control beliefs most strongly
      correlated with intentions to test regularly for chlamydia were beliefs about
      stopping the spread of infection, partners' behaviour and the availability of
      testing. These beliefs represent potential targets for interventions to increase
      chlamydia testing among young people living in deprived areas.

PMID- 24287802
TI  - Theory of mind deficit in adult patients with congenital heart disease.
AB  - This article provides the first assessment of theory of mind, that is, the
      ability to reason about mental states, in adult patients with congenital heart
      disease. Patients with congenital heart disease and matched healthy controls were
      administered classical theory of mind tasks and a semi-structured interview which
      provides a multidimensional evaluation of theory of mind (Theory of Mind
      Assessment Scale). The patients with congenital heart disease performed worse
      than the controls on the Theory of Mind Assessment Scale, whereas they did as
      well as the control group on the classical theory-of-mind tasks. These findings
      provide the first evidence that adults with congenital heart disease may display
      specific impairments in theory of mind. 

PMID- 24287803
TI  - The association between resilience and diabetic neuropathy by socioeconomic
      position: cross-sectional findings from the KORA-Age study.
AB  - We investigated whether older adults with diabetes mellitus and lower resilience
      have an increased risk of diabetic neuropathy as compared to older adults with
      higher resilience, and whether this association varies by socioeconomic position.
      In total, 3942 individuals took part in a health survey in Augsburg, Germany, in
      2008-2010 (KORA-Age study). We found that among participants with low
      socioeconomic position, those with higher resilience had a lower probability of
      suffering from neuropathy as compared to participants with lower resilience
      (absolute risk reduction = 10%). Adjusted odds ratio with 95% confidence
      intervals for the outcome diabetic neuropathy also showed that lower resilience
      scores had an independent effect in increasing the risk of diabetic neuropathy
      among elderly individuals with a low socioeconomic position (odds ratio: 1.83;
      confidence interval: 1.09-3.08). Health-promoting strategies focussing on
      resilience should be further explored.

PMID- 24287804
TI  - Science is the drug.

PMID- 24287805
TI  - Three sides of a coin.

PMID- 24287806
TI  - Detection of human papillomavirus type 56 in giant condyloma acuminatum.

PMID- 24287807
TI  - Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch
      hospitals.
AB  - PURPOSE: To assess current antithrombotic treatment strategies in the Netherlands
      in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS:
      For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist
      experienced in performing TAVI was interviewed concerning heparin, aspirin,
      thienopyridine and oral anticoagulation treatment in patients undergoing TAVI.
      RESULTS: The response rate was 100 %. In every centre, a protocol for
      antithrombotic treatment after TAVI was available. Aspirin was prescribed in all
      centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of
      concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres,
      duration of concomitant clopidogrel was based upon type of prosthesis: 6 months
      versus 3 months for supra-annular and intra-annular prostheses, respectively.
      CONCLUSIONS: Leaning on a small basis of evidence and recommendations, the
      antithrombotic policy for patients undergoing TAVI is highly variable in the
      Netherlands. As a standardised regimen might further reduce haemorrhagic
      complications, large randomised clinical trials may help to establish the most
      appropriate approach.

PMID- 24287808
TI  - Percutaneous occlusion of post-myocardial infarction ventricular septum rupture.
AB  - AIMS: The aim of this systematic review is to gain insight into the published
      experience on percutaneous closure of a post-infarction ventricular septal
      rupture (VSR). METHOD: Relevant literature was obtained by MeSH-term searches in
      the online search-engine PubMed. Articles published in the last 10 years were
      included. Further filtering was done by using search limits and individual
      article selection based on the aims of this systematic review. CONCLUSION:
      Percutaneous closure is a potential technique in a select group of patients. The
      presence of cardiogenic shock and closure in the acute phase after VSR diagnosis
      are important risk factors of mortality. Device implantation is in general
      successful with few procedure-related complications. Reduction of the shunt
      fraction has been reported frequently. This technique is a less invasive
      alternative to surgical treatment and should be applied on a case-by-case basis.

PMID- 24287809
TI  - Molecular imaging of coronary atherosclerosis; predictive of an acute myocardial
      infarction?

PMID- 24287810
TI  - Do root hydraulic properties change during the early vegetative stage of plant
      development in barley (Hordeum vulgare)?
AB  - BACKGROUND AND AIMS: As annual crops develop, transpirational water loss
      increases substantially. This increase has to be matched by an increase in water
      uptake through the root system. The aim of this study was to assess the
      contributions of changes in intrinsic root hydraulic conductivity (Lp, water
      uptake per unit root surface area, driving force and time), driving force and
      root surface area to developmental increases in root water uptake. METHODS:
      Hydroponically grown barley plants were analysed during four windows of their
      vegetative stage of development, when they were 9-13, 14-18, 19-23 and 24-28 d
      old. Hydraulic conductivity was determined for individual roots (Lp) and for
      entire root systems (Lp(r)). Osmotic Lp of individual seminal and adventitious
      roots and osmotic Lp(r) of the root system were determined in exudation
      experiments. Hydrostatic Lp of individual roots was determined by root pressure
      probe analyses, and hydrostatic Lp(r) of the root system was derived from
      analyses of transpiring plants. KEY RESULTS: Although osmotic and hydrostatic Lp
      and Lp(r) values increased initially during development and were correlated
      positively with plant transpiration rate, their overall developmental increases
      (about 2-fold) were small compared with increases in transpirational water loss
      and root surface area (about 10- to 40-fold). The water potential gradient
      driving water uptake in transpiring plants more than doubled during development,
      and potentially contributed to the increases in plant water flow. Osmotic Lp(r)
      of entire root systems and hydrostatic Lp(r) of transpiring plants were similar,
      suggesting that the main radial transport path in roots was the cell-to-cell path
      at all developmental stages. CONCLUSIONS: Increase in the surface area of root
      system, and not changes in intrinsic root hydraulic properties, is the main means
      through which barley plants grown hydroponically sustain an increase in
      transpirational water loss during their vegetative development.

PMID- 24287811
TI  - Ontogenetic tissue modification in Malus fruit peduncles: the role of sclereids.
AB  - BACKGROUND AND AIMS: Apple (Malus) fruit peduncles are highly modified stems with
      limited secondary growth because fruit ripening lasts only one season. They must
      reliably connect rather heavy fruits to the branch and cope with increasing fruit
      weight, which induces dynamic stresses under oscillating wind loads. This study
      focuses on tissue modification of these small, exposed structures during fruit
      development. METHODS: A combination of microscopic, static and dynamic mechanical
      tests, as well as Raman spectroscopy, was used to study structure-function
      relationships in peduncles of one cultivar and 12 wild species, representatively
      chosen from all sections of the genus Malus. Tissue differentiation and
      ontogenetic changes in mechanical properties of Malus peduncles were observed
      throughout one growing season and after successive removal of tissues. KEY
      RESULTS: Unlike in regular stems, the vascular cambium produces mainly phloem
      during secondary growth. Hence, in addition to a reduced xylem, all species
      developed a centrally arranged sclerenchyma ring composed of fibres and
      brachysclereids. Based on differences in cell-wall thickness, and proportions and
      arrangement of sclereids, two types of peduncle construction could be
      distinguished. Fibres provide an increased maximum tensile strength and
      contribute most to the overall axial rigidity of the peduncles. Sclereids
      contribute insignificantly to peduncle strength; however, despite being shown to
      have a lower elastic modulus than fibres, they are the most effective tissue in
      stiffening peduncles against bending. CONCLUSIONS: The experimental data revealed
      that sclereids originating from cortical parenchyma act as 'accessory' cells to
      enhance proportions of sclerenchyma during secondary growth in peduncles. The
      mechanism can be interpreted as an adaptation to continuously increasing fruit
      loads. Under oscillating longitudinal stresses, sclereids may be regarded as
      regulating elements between maintenance of stiffness and viscous damping, the
      latter property being attributed to the cortical parenchyma.

PMID- 24287812
TI  - Sensitivity of growth and biomass allocation patterns to increasing nitrogen: a
      comparison between ephemerals and annuals in the Gurbantunggut Desert, north
      western China.
AB  - BACKGROUND AND AIMS: Biomass accumulation and allocation patterns are critical to
      quantifying ecosystem dynamics. However, these patterns differ among species, and
      they can change in response to nutrient availability even among genetically
      related individuals. In order to understand this complexity further, this study
      examined three ephemeral species (with very short vegetative growth periods) and
      three annual species (with significantly longer vegetative growth periods) in the
      Gurbantunggut Desert, north-western China, to determine their responses to
      different nitrogen (N) supplements under natural conditions. METHODS: Nitrogen
      was added to the soil at rates of 0, 0.5, 1.0, 3.0, 6.0 and 24.0 g N m(-2) year(
      1). Plants were sampled at various intervals to measure relative growth rate and
      shoot and root dry mass. KEY RESULTS: Compared with annuals, ephemerals grew more
      rapidly, increased shoot and root biomass with increasing N application rates and
      significantly decreased root/shoot ratios. Nevertheless, changes in the biomass
      allocation of some species (i.e. Erodium oxyrrhynchum) in response to the N
      treatment were largely a consequence of changes in overall plant size, which was
      inconsistent with an optimal partitioning model. An isometric log shoot vs. log
      root scaling relationship for the final biomass harvest was observed for each
      species and all annuals, while pooled data of three ephemerals showed an
      allometric scaling relationship. CONCLUSIONS: These results indicate that
      ephemerals and annuals differ observably in their biomass allocation patterns in
      response to soil N supplements, although an isometric log shoot vs. log root
      scaling relationship was maintained across all species. These findings highlight
      that different life history strategies behave differently in response to N
      application even when interspecific scaling relationships remain nearly
      isometric.

PMID- 24287814
TI  - Optofluidic router based on tunable liquid-liquid mirrors.
AB  - We present an electrically tunable 1 * 5 optofluidic router for on-chip light
      routing. The device can redirect light from an optical input channel into five
      output channels by exploiting total internal reflection (TIR) at a liquid-liquid
      interface. The liquid-liquid mirrors, demonstrated for the first time, are tuned
      using integrated electrowetting-on-dielectrics (EWOD) actuators. The router is
      assembled from two chips fabricated by standard MEMS techniques. Through a
      combination of microfluidic with micro-optical components on chip, reliable light
      routing is achieved with switching times of [1.5-3.3] s, efficiencies of coupling
      into channels of up to 12%, optical cross-talk as low as -24 dB, a required drive
      voltage of 50 V, and a low power consumption of <5 mW, using a device 12 * 13 * 2
      mm(3) in size. The optofluidic approach enables addressing of multiple channels
      over a broad wavelength range. Such optical routing capabilities are important
      for lab-on-chip devices focusing on optical spectroscopy, optical detection, or
      even optical manipulation. When integrated with external light sources and a low
      cost disposable photonic lab-on-a-chip, the router could thus lead to novel
      laboratory measurement systems. 

PMID- 24287813
TI  - Clonal growth is enhanced in the absence of a mating morph: a comparative study
      of fertile stylar polymorphic and sterile monomorphic populations of Nymphoides
      montana (Menyanthaceae).
AB  - BACKGROUND AND AIMS: Many aquatic species with stylar polymorphisms have the
      capacity for clonal and sexual reproduction and are sensitive to the balance of
      the two reproductive modes when there are a limited number of mating morphs
      within a population. This study asked how the clonal and sexual reproductive
      modes perform in populations that contain only a single morph and where fitness
      gain through sexual reproduction is rare. In clonal aquatic Nymphoides montana,
      polymorphic populations normally contain two mating morphs in equal frequencies.
      Populations are sexually fertile and appear to be maintained by pollen transfer
      between the two partners. However, in a monomorphic population of N. montana
      where mating opportunities are unavailable, female and male function is impaired
      and clonality maintains the population. Here, the consequences of intraspecific
      variation in sexuality were explored between monomorphic and polymorphic N.
      montana populations in eastern Australia. METHODS: Comparative measurements of
      male and female fertility, total dry mass and genotypic diversity using ISSR
      markers were made between populations with variable sexuality. KEY RESULTS AND
      CONCLUSIONS: Very few seeds were produced in the monomorphic population under
      natural and glasshouse conditions due to dysfunctional pollen and ovules. Stigma
      anther separation was minimal in the monomorphic population, which may be a
      consequence of the relaxed selective pressures that regulate the maintenance of
      sexual function. However, clonal reproduction was favoured at the expense of
      sexual reproduction in the monomorphic population; this may facilitate the
      establishment of sterility throughout the population via resource reallocation or
      pleiotropic effects. The ISSR results showed that the monomorphic population was
      one large, single genotype, unlike the multi-genotypic fertile polymorphic
      populations. Evolutionary loss of sex in a clonal population in which a mating
      morph is absent was evident; under these conditions clonal growth may assure
      reproduction and expand the population via spreading stolons.

PMID- 24287815
TI  - Synthesis, characterization, optical absorption/fluorescence spectroscopy, and
      second-order nonlinear optical properties of aggregate molecular architectures of
      unsymmetrical Schiff-base zinc(II) complexes.
AB  - This paper reports the synthesis and a detailed investigation in solution,
      through (1)H NMR, optical absorption, fluorescence spectroscopy and second-order
      nonlinear optical studies, on the structure and photophysical properties of a
      series of unsymmetrical alkoxy-derivatized Schiff-base Zn(II) species bearing on
      one side an alkyl ammonium bromide as a Lewis base. Overall results suggest that
      these complexes are present in solution of dichloromethane as dimeric aggregates
      in which each molecular unit mutually interacts with another unit through
      intermolecular Zn...Br(-) interactions. This represents an alternative approach
      to control the supramolecular architecture of Lewis acidic, Schiff-base Zn(II)
      complexes.

PMID- 24287816
TI  - Can chemokines be used as biomarkers for endometriosis? A systematic review.
AB  - STUDY QUESTION: Can we use chemokines as biomarkers to diagnose patients with
      endometriosis in clinical practice? SUMMARY ANSWER: Some chemokines, especially
      CXCL8 (IL-8), CCL-2 (MCP-1) and CCL5 (RANTES), have the potential to work as
      biomarkers to identify patients with endometriosis but their accuracy could be
      improved by combination with other non-inflammatory markers in a panel of
      biomarkers. WHAT IS ALREADY KNOWN: The need for a good marker to diagnose
      endometriosis has increased in recent years and research in this field has
      intensified. Chemokines have been reported to be associated with endometriosis in
      several studies over the last 20 years. Many of these studies measured one or
      more chemokines in peritoneal fluid (PF) and peripheral blood (PB) or through
      endometrial biopsies in patients with and without endometriosis. STUDY DESIGN,
      SIZE, DURATION: A systematic review was done on all published studies that
      compared chemokine concentrations in patients with and without endometriosis to
      evaluate their potential as biomarkers for the disease. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Using MEDLINE database from December 1993 to August 2013 and
      the MeSH terms 'Endometriosis' and 'Chemokines', we identified relevant studies
      to include in the present review, which was based on the PRISMA statement.
      Studies that measured at least one chemokine in patients with endometriosis and
      matching controls in PB, PF or endometrial samples were included. We did not
      include samples from ectopic lesions. All review articles as well as studies with
      animals and those not written in English were excluded from this systematic
      review. The studies were assessed using a modified version of the Quality
      Assessment of Diagnostic Accuracy Studies criteria. Two authors independently
      assessed studies for inclusion and risk of bias, and extracted data. MAIN RESULTS
      AND THE ROLE OF CHANCE: After inclusion and exclusion criteria, 62 studies were
      selected to be included in this systematic review. A total of 27 different
      chemokines or their receptors were evaluated in the reviewed studies. The most
      studied chemokines (including their receptors) were CXCL8 (51.6%), CCL2 (38.7%)
      and CCL5 (19.3%) (% of studies). CXCL8 (IL-8) appears to have the best results
      among all the other chemokines as a marker for endometriosis. LIMITATIONS,
      REASONS FOR CAUTION: Some studies included have low power due to small sample
      size and study designs vary in the assessment criteria for the markers, the state
      of the patients (e.g. phase of the cycle and stage of disease) and the nature of
      the controls. WIDER IMPLICATIONS OF THE FINDINGS: Our findings could guide future
      research in this field to select the chemokines with the best potential, and to
      stimulate better-designed studies to determine whether they can become a useful
      diagnostic tool in clinical practice. STUDY FUNDING/COMPETING INTEREST(S): There
      was no funding to support this systematic review. The authors have no competing
      interest to declare.

PMID- 24287817
TI  - Moderate alcohol intake and menstrual cycle characteristics.
AB  - STUDY QUESTION: Does moderate alcohol intake affect menstrual cycle
      characteristics among women in the Danish population? SUMMARY ANSWER: Levels of
      alcohol exposure as seen in this study do not substantially affect the menstrual
      cycle. WHAT IS KNOWN ALREADY: Animal studies indicate alcohol-induced disruptions
      of the reproductive system, but previous epidemiological studies addressing the
      possible association between alcohol intake and the menstrual cycle are sparse.
      STUDY DESIGN, SIZE, DURATION: A cross-sectional study with retrospectively
      collected data including 82 146 pregnant Danish women in the Danish National
      Birth Cohort (DNBC) enrolled during the years 1996-2002. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Information on weekly alcohol consumption and menstrual cycle
      characteristics before pregnancy was obtained through a computer-assisted
      telephone interview in pregnancy Week 12-16. The associations between weekly
      alcohol consumption and menstrual cycle irregularity (>=7 days difference between
      cycles) and length (short cycle: <=24 days, long cycle: >=32 days) were analysed
      using logistic regression with weekly alcohol intake categorized into abstainers
      (0 drinks per week), low (0.5-2.0 drinks per week), moderate (2.5-14.0 drinks per
      week) and high (14.0-86.5 drinks per week). Estimates are given as adjusted odds
      ratios with 95% confidence intervals. MAIN RESULTS AND THE ROLE OF CHANCE: The
      overall participation rate was 60% of the women invited. We found that a high
      weekly alcohol consumption was not associated with menstrual cycle disturbances.
      We observed higher odds of irregular and short cycles among abstainers when
      compared with women with a low weekly alcohol consumption, but found no trend of
      more cycle disturbances with higher alcohol consumption. LIMITATIONS, REASONS FOR
      CAUTION: Possible limitations in our study include a risk of selection bias due
      to the moderate participation rate and the use of retrospective information on
      alcohol exposure and menstrual cycle characteristics before getting pregnant. The
      higher odds of irregular and short cycles among abstainers may reflect other
      health problems in these women rather than an actual effect of alcohol on the
      menstrual cycle. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the
      study results is restricted to women who manage to conceive and women who do not
      use oral contraceptives within 2 months before getting pregnant. This study
      suggests that the menstrual cycle is not substantially affected by higher alcohol
      consumption among the participating women. STUDY FUNDING/COMPETING INTEREST(S):
      Supported by a scholarship from Aarhus University Research Foundation. The Danish
      National Research Foundation has established the Danish Epidemiology Science
      Centre that initiated and created the DNBC. The cohort is furthermore a result of
      a major grant from this Foundation. Additional support for the DNBC is obtained
      from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth
      Defects Foundation, the Augustinus Foundation and the Health Foundation. No
      conflict of interest declared.

PMID- 24287818
TI  - Are patients at risk for psychological maladjustment during fertility treatment
      less willing to comply with treatment? Results from the Portuguese validation of
      the SCREENIVF.
AB  - STUDY QUESTION: Do patients at risk for psychological maladjustment during
      fertility treatment present lower intentions to comply with recommended treatment
      than patients not at risk? SUMMARY ANSWER: Patients at risk of psychological
      maladjustment present similar high intentions to comply with recommended
      fertility treatment to those not at risk but their intentions are conditioned by
      the degree of control they perceive over their fertility and its treatment and
      their capacity to accept a future without biological children. WHAT IS KNOWN
      ALREADY: Infertile couples refer to the psychological burden of treatment as one
      of the most important reasons for withdrawal from recommended treatment. The
      SCREENIVF can be used before treatment to screen patients at risk for
      psychological maladjustment by assessing five risk factors: anxiety, depression,
      helplessness and lack of acceptance cognitions and social support. STUDY DESIGN,
      SIZE, DURATION: Cross-sectional study. First, we investigated the psychometric
      properties of the Portuguese version of the SCREENIVF. Secondly, we investigated
      associations between risk for psychological maladjustment and intentions to
      comply with treatment. PARTICIPANTS/ MATERIALS, SETTING, METHODS: Two hundred and
      ninety-one women and 92 men undergoing any stage of fertility treatment at
      Portuguese infertility clinics were recruited online or in the clinical setting
      (55% response rate). Participants completed questionnaires that assessed their
      emotional adjustment, quality of life and compliance intentions. MAIN RESULTS AND
      ROLE OF CHANCE: The confirmatory factor analysis for the SCREENIVF indicated good
      fit [chi(2) = 188.50, P < 0.001; comparative fit index = 0.97; root-mean-square
      error of approximation = 0.06 (90% CI 0.05-0.07)] and all dimensions were
      reliable (alpha >= 0.70, except depression for men: alpha = 0.66). Fifty-two
      percent of women and 30% of men were at risk for maladjustment. Women and men at
      risk and not at risk for maladjustment reported similar intentions to comply with
      treatment (P > 0.05). Cognitive risk factors moderated negative associations
      found between distress and compliance intentions. Higher anxiety was associated
      with lower compliance intentions for patients with lower helplessness cognitions
      (beta = -0.45, P = 0.01) and men with higher acceptance cognitions (beta = -0.60;
      P = 0.03), but not for patients with higher helplessness cognitions (beta = 0.25,
      P = 0.13) and men with lower acceptance cognitions (beta = 0.38; P = 0.21).
      Higher depression was associated with lower compliance intentions for patients
      with higher helplessness cognitions (beta = -0.33, P = 0.02), but not for
      patients with lower helplessness cognitions (beta = 0.19, P = 0.30). LIMITATIONS,
      REASONS FOR CAUTION: Few men participated and thus only medium-to-large effect
      sizes could be detected for them. Forty-eight percent of participants were
      recruited online and this could have resulted in higher rates of patients at
      risk. WIDER IMPLICATIONS OF THE FINDINGS: The SCREENIVF is not useful to identify
      patients at risk for non-compliance. However, the clinic staff should be aware
      that patients who score high on helplessness cognitions and low on acceptance may
      need additional decisional aid to make autonomous and satisfying decisions about
      uptake of treatment. The Portuguese version of the SCREENIVF is valid and
      reliable and can be used with women undergoing any type of fertility treatment.
      STUDY FUNDING/ COMPETING INTEREST(S): S.G. received a postdoctoral fellowship
      from the Portuguese Foundation for Science and Technology (FCT
      SFRH/BPD/63063/2009). There are no conflicts of interest to declare.

PMID- 24287819
TI  - Dopamine in human follicular fluid is associated with cellular uptake and
      metabolism-dependent generation of reactive oxygen species in granulosa cells:
      implications for physiology and pathology.
AB  - STUDY QUESTION: Is the neurotransmitter dopamine (DA) in the human ovary involved
      in the generation of reactive oxygen species (ROS)? SUMMARY ANSWER: Human ovarian
      follicular fluid contains DA, which causes the generation of ROS in cultured
      human granulosa cells (GCs), and alterations of DA levels in follicular fluid and
      DA uptake/metabolism in GCs in patients with polycystic ovary syndrome (PCOS) are
      linked to increased levels of ROS. WHAT IS KNOWN ALREADY: DA is an important
      neurotransmitter in the brain, and the metabolism of DA results in the generation
      of ROS. DA was detected in human ovarian homogenates, but whether it is present
      in follicular fluid and plays a role in the follicle is not known. STUDY DESIGN,
      SIZE AND DURATION: We used human follicular fluid from patients undergoing in
      vitro fertilization (IVF), GCs from patients with or without PCOS and also
      employed mathematical modeling to investigate the presence of DA and its effects
      on ROS. PARTICIPANTS/MATERIALS, SETTING AND METHODS: DA in follicular fluid and
      GCs was determined by enzyme-linked immunosorbent assay. GC viability, apoptosis
      and generation of ROS were monitored in GCs upon addition of DA. Inhibitors of DA
      uptake and metabolism, an antioxidant and DA receptor agonists, were used to
      study cellular uptake and the mechanism of DA-induced ROS generation. Human GCs
      were examined for the presence and abundance of transcripts of the DA transporter
      (DAT; SLC6A3), the DA-metabolizing enzymes monoamine oxidases A/B (MAO-A/B) and
      catechol-O-methyltransferase and the vesicular monoamine transporter. A
      computational model was developed to describe and predict DA-induced ROS
      generation in human GCs. MAIN RESULTS AND ROLE OF CHANCE: We found DA in
      follicular fluid of ovulatory follicles of the human ovary and in GCs. DAT and
      MAO-A/B, which are expressed by GCs, are prerequisites for a DA receptor
      independent generation of ROS in GCs. Blockers of DAT and MAO-A/B, as well as an
      antioxidant, prevented the generation of ROS (P < 0.05). Agonists of DA receptors
      (D1 and D2) did not induce ROS. DA, in the concentration range found in
      follicular fluid, did not induce apoptosis of cultured GCs. Computational
      modeling suggested, however, that ROS levels in GCs depend on the concentrations
      of DA and on the cellular uptake and metabolism. In PCOS-derived follicular
      fluid, the levels of DA were higher (P < 0.05) in GCs, the transcript levels of
      DAT and MAO-A/B in GCs were 2-fold higher (P < 0.05) and the DA-induced ROS
      levels were found to be more than 4-fold increased (P < 0.05) compared with non
      PCOS cells. Furthermore, DA at a high concentration induced apoptosis in PCOS
      derived GCs. LIMITATIONS, REASONS FOR CAUTION: While the results in IVF-derived
      follicular fluid and in GCs reveal for the first time the presence of DA in the
      human follicular compartment, functions of DA could only be studied in IVF
      derived GCs, which can be viewed as a cellular model for the periovulatory
      follicular phase. The full functional importance of DA-induced ROS in small
      follicles and other compartments of the ovary, especially in PCOS samples,
      remains to be shown. WIDER IMPLICATIONS OF THE FINDINGS: The results identify DA
      as a factor in the human ovary, which, via ROS generation, could play a role in
      ovarian physiology and pathology. The results obtained in samples from women with
      PCOS suggest the involvement of DA, acting via ROS, in this condition. STUDY
      FUNDING/COMPETING INTERESTS: This work was supported by a grant from DFG
      MA1080/17-3 and in part MA1080/19-1. There are no competing interests.

PMID- 24287820
TI  - First trimester size charts of embryonic brain structures.
AB  - STUDY QUESTION: Can reliable size charts of human embryonic brain structures be
      created from three-dimensional ultrasound (3D-US) visualizations? SUMMARY ANSWER:
      Reliable size charts of human embryonic brain structures can be created from high
      quality images. WHAT IS KNOWN ALREADY: Previous studies on the visualization of
      both the cavities and the walls of the brain compartments were performed using 2D
      US, 3D-US or invasive intrauterine sonography. However, the walls of the
      diencephalon, mesencephalon and telencephalon have not been measured non
      invasively before. Last-decade improvements in transvaginal ultrasound techniques
      allow a better visualization and offer the tools to measure these human embryonic
      brain structures with precision. STUDY DESIGN, SIZE, DURATION: This study is
      embedded in a prospective periconceptional cohort study. A total of 141
      pregnancies were included before the sixth week of gestation and were monitored
      until delivery to assess complications and adverse outcomes.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: For the analysis of embryonic growth,
      596 3D-US scans encompassing the entire embryo were obtained from 106 singleton
      non-malformed live birth pregnancies between 7(+0) and 12(+6) weeks' gestational
      age (GA). Using 4D View (3D software) the measured embryonic brain structures
      comprised thickness of the diencephalon, mesencephalon and telencephalon, and the
      total diameter of the diencephalon and mesencephalon. MAIN RESULTS AND THE ROLE
      OF CHANCE: Of 596 3D scans, 161 (27%) high-quality scans of 79 pregnancies were
      eligible for analysis. The reliability of all embryonic brain structure
      measurements, based on the intra-class correlation coefficients (ICCs) (all above
      0.98), was excellent. Bland-Altman plots showed moderate agreement for
      measurements of the telencephalon, but for all other measurements the agreement
      was good. Size charts were constructed according to crown-rump length (CRL).
      LIMITATIONS, REASONS FOR CAUTION: The percentage of high-quality scans suitable
      for analysis of these brain structures was low (27%). WIDER IMPLICATIONS OF THE
      FINDINGS:  The size charts of human embryonic brain structures can be used to
      study normal and abnormal development of brain development in future. Also, the
      effects of periconceptional maternal exposures, such as folic acid supplement use
      and smoking, on human embryonic brain development can be a topic of future
      research. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the
      Department of Obstetrics and Gynaecology of the Erasmus University Medical
      Center. M.G. was supported by an additional grant from the Sophia Foundation for
      Medical Research (SSWO grant number 644). No competing interests are declared.

PMID- 24287821
TI  - Quality of care in an IVF programme from a patient's perspective: development of
      a validated instrument.
AB  - STUDY QUESTION: Is it possible to develop a trustworthy instrument to evaluate
      the patient's perspective on fertility care and to document fully all
      methodological steps, including validation? SUMMARY ANSWER: A validated
      instrument has been developed for both women and men undergoing assisted
      reproduction to monitor the quality of care on a regular basis, similar to live
      birth rates and other effectiveness data. WHAT IS KNOWN ALREADY?: Within
      fertility care, several instruments have been developed, but many have
      significant methodological problems and few have been validated. Most instruments
      focus exclusively on women and no questionnaires have been directed at women and
      men separately. STUDY DESIGN, SIZE AND DURATION: The questionnaire specific to
      IVF treatments (QPP-IVF) is based on the theoretical foundation of the validated
      general instrument, quality of care from patients perspective (QPP), for both
      women and men. The QPP-IVF was developed and validated by quantitative methods. A
      two-centre study ran between September 2011 and May 2012. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: In all, 655 women and men participated. The measurements
      consisted of two kinds of evaluations: the rating of perceived reality of care
      and the rating of the subjective importance of various aspects of treatment. The
      questionnaire consisted of 43 items for women and 42 items for men. An
      exploratory factor analysis was performed for women for all items of subjective
      importance. Eigenvalue, explained variance and factor loading are given for each
      factor. Internal consistency of subscales was assessed by Cronbach's alpha, item
      discriminant validity and percentage scaling success. For external validity, a
      correlation with fertility quality of life (FertiQoL) was performed and for
      reliability, a test-retest analysis was carried out. Sensitivity analyses were
      performed by known-group analyses. All significance tests were two sided and
      conducted at the 5% significance level. MAIN RESULTS AND THE ROLE OF CHANCE: The
      QPP-IVF instrument, divided into four dimensions, seemed a valid and reliable way
      of measuring the quality of care from a patient's perspective, for both women and
      men. The item-scaling test confirmed 10 underlying factors, with scaling success
      in all subscales and Cronbach's alpha >0.70 for women in almost all subscales. It
      was somewhat lower for men but still acceptable. The external validity was
      acceptable, with significant correlation between QPP-IVF and FertiQoL. The test
      retest analysis confirmed that QPP-IVF was a stable instrument, with intra-class
      correlation coefficients from 0.74 to 0.89 for women. Sensitivity analyses
      indicated a sensitive instrument. LIMITATIONS, REASON FOR CAUTION: The response
      rate to the questionnaire was 67.5%. Although considered acceptable in
      questionnaire studies, this response level might introduce a certain risk of
      selection bias. The questionnaire was developed and validated only in Sweden.
      WIDER IMPLICATIONS OF THE FINDINGS: The QPP-IVF may be of use for purposes of
      quality improvement and national comparisons. Future studies should focus on
      establishing the QPP-IVF as a valuable instrument for measuring the quality of
      care outside Sweden. STUDY FUNDING/COMPETING INTEREST: The study was supported by
      the LUA/ALF agreement at Sahlgrenska University Hospital, Gothenburg, Sweden and
      by Hjalmar Svensson's Research Foundation. None of the authors declared any
      conflict of interests.

PMID- 24287822
TI  - Diverse influences of androgen-disrupting chemicals on immune responses mounted
      by macrophages.
AB  - Androgen-disrupting chemicals (ADCs) can alter male sexual development. Although
      the effects of ADCs on hormone disruption have been studied, their influence on
      the immune response is not fully understood. To investigate the effects of ADCs
      on innate immunity, we tested eight candidate ADCs for their influence on
      macrophages by measuring nitric oxide (NO) production and cell viability. Our
      results showed that treatment with a mixture of lipopolysaccharide and
      hexachlorobenzene increased NO production in RAW 264.7 cells, a murine macrophage
      cell line. In contrast, compared to exposure to a negative control, exposure to
      di-2-ethylhexyl adipate (DEHA), benzylbutyl phthalate (BBP), testosterone (TTT),
      or permethrin decreased NO production. DEHA, BBP, and TTT inhibited NO production
      in an inducible nitric oxide synthase-dependent manner. Treatment with bisphenol
      A (BPA), nonylphenol (NNP), or tributyltin chloride (TBTC) reduced NO production
      and induced cell death. While BPA induced RAW 264.7 cell death through apoptosis,
      NNP and TBTC caused cell death through necrosis. These results offer insights
      into the influences of ADCs on the innate immune system. 

PMID- 24287823
TI  - Effect of IL-15 and natural killer cells on osteoclasts and osteoblasts in a
      mouse coculture.
AB  - This study analyzes the effect of interleukin-15 (IL-15) on osteoclast formation
      using a coculture of mouse osteoblasts and bone marrow cells (BMCs) stimulated
      with prostaglandin E2 (PGE2), which both have important role in rheumatoid
      arthritis (RA) and periodontal disease (PD). BMCs isolate lacking T (BM(T-)) or
      NK (BM(NK-)) cells, BMCs with no cells removed (BM(T+NK+)), purified NK cells,
      and purified T cells were each cocultured with osteoblasts in the presence or
      absence of PGE2 and/or IL-15. The number of both osteoclasts and osteoblasts was
      decreased by IL-15 in a dose-dependent manner in BM(T+NK+), BM(T-). However, the
      reductions were improved in BM(NK-). The expression of caspase3 in osteoblasts
      cocultured with NK cells was increased in a dose-dependent manner by IL-15. IL-15
      stimulates apoptosis of osteoblasts via activation of NK cells. Since osteoblasts
      have an important role in bone formation, IL-15 may be an inflammatory bone
      destructive factor in RA and PD. 

PMID- 24287824
TI  - Only the best is good enough.

PMID- 24287825
TI  - [Improved prenatal diagnosis?].

PMID- 24287826
TI  - [Centralization of the pelvic reservoir surgery].

PMID- 24287827
TI  - [Electroconvulsive therapy out of control?].

PMID- 24287828
TI  - [Questionable criticism of electroconvulsive therapy].

PMID- 24287829
TI  - [R. Fosse replies].

PMID- 24287831
TI  - [Dirty games around the introduction of grades].

PMID- 24287832
TI  - [New guidelines for head injuries].

PMID- 24287835
TI  - [Medical students' attitudes towards legalisation of euthanasia and physician
      assisted suicide].
AB  - BACKGROUND: We wished to investigate prevailing attitudes among future doctors
      regarding legalisation of euthanasia and physician-assisted suicide. This issue
      is important, since any legalisation of these practices would confer a completely
      new role on doctors. MATERIAL AND METHOD: Attitudes were identified with the aid
      of a questionnaire-based survey among medical students in their 5th and 6th year
      of study in the four Norwegian medical schools. RESULTS: Altogether 531 students
      responded (59.5% of all students in these cohorts). Of these, 102 (19%) were of
      the opinion that euthanasia should be legalised in the case of terminal illness,
      164 (31%) responded that physician-assisted suicide should be permitted for this
      indication, while 145 (28%) did not know. A minority of the respondents would
      permit euthanasia and physician-assisted suicide in other situations. Women and
      those who reported that religion was important to them were less positive than
      men to permitting euthanasia or physician-assisted suicide. INTERPRETATION: In
      most of the situations described, the majority of the students in this survey
      rejected legalisation. Opinions are more divided in the case of terminal illness,
      since a larger proportion is in favour of legalisation and more respondents are
      undecided.

PMID- 24287836
TI  - Currarino syndrome at Rikshospitalet 1961-2012.
AB  - BACKGROUND: Currarino syndrome is a rare hereditary condition with constipation
      as the main symptom. The typical patient has a combination of sacral, anorectal,
      intraspinal and presacral anomalies. Familial cases most often have a mutation in
      the MNX1 gene. The majority of Norwegian Currarino patients are treated at
      Rikshospitalet. This article gives an account of 50 years of experience with the
      condition. MATERIAL AND METHOD: The study is based on the medical records of
      patients with Currarino syndrome, as well as some first-degree relatives, from
      the period 1961-2012. We recorded the results of mutation analysis, X-ray of the
      sacrum, and ultrasound, MRI and/or CT scans, as well as the treatments
      administered. RESULTS: We treated 29 patients over the period in question, and in
      addition identified seven healthy relatives with a mutation in MNX1 and one
      relative with a pathognomonic sacral anomaly. There were 15 familial and 14
      sporadic cases. Fourteen familial cases and one of the sporadic cases were shown
      to have a mutation in the MNX1 gene. Phenotypic variation was pronounced, and we
      saw no obvious correlation between genotype and phenotype. Twenty-six of the
      patients had constipation and 15 underwent a colostomy. Fourteen patients
      required neurosurgical and seven urogenital interventions. No patients had
      malignant disease. INTERPRETATION: Patients with Currarino syndrome have a highly
      variable clinical presentation with constipation as the main problem. In patients
      with a familial syndrome, a mutation in the MNX1 gene can be expected.

PMID- 24287837
TI  - Umbilical cord clamping at birth--practice in Norwegian maternity wards.
AB  - BACKGROUND: The timing and practice used for umbilical cord clamping of neonates
      are controversial internationally as well as in Norway. We therefore wished to
      investigate routines and practices for umbilical cord clamping of neonates in
      Norway. MATERIAL AND METHOD: A web-based questionnaire was sent to heads of
      departments of all maternity wards in Norway (n = 52). They were asked about
      their practice with regard to umbilical cord clamping of neonates and whether
      written routines had been prepared for this purpose. We defined early umbilical
      cord clamping as immediate or within 30 seconds and late clamping as >= 1 minute
      or not until pulsation in the umbilical cord had ceased. RESULTS: Fifty (96%) of
      the maternity institutions returned a completed questionnaire. Twelve
      institutions (24%) reported to clamp the umbilical cord of full-term neonates
      early, and 38 (76%) reported to practise late clamping. Nineteen maternity wards
      (38%) followed written routines for umbilical cord clamping of full-term
      neonates, and among these, early umbilical cord clamping was practised in nine
      (47%). In the 31 maternity wards that had no written routines, early umbilical
      cord clamping was practised in three (10%). Twenty-seven of the maternity wards
      reported that the child is placed on the maternal abdomen before clamping of the
      umbilical cord, 14 reported that the child commonly is held below the introitus
      before umbilical cord clamping, and the rest did not report any consistent
      practice. INTERPRETATION: There is wide variation in the practice for umbilical
      cord clamping in Norwegian maternity wards, many of which have no written
      guidelines. We argue that national guidelines for umbilical cord clamping of
      neonates should be established.

PMID- 24287838
TI  - Influenza vaccine--for whom?

PMID- 24287839
TI  - [Images of thought are my sleeping pills].

PMID- 24287840
TI  - [Sleep].

PMID- 24287841
TI  - [Pruritus sese exhibiendi].

PMID- 24287843
TI  - [Scandinavian guidelines for the acute management of adult patients with minimal,
      mild, or moderate head injuries].
AB  - BACKGROUND In 2000, the Scandinavian Neurotrauma Committee (SNC) published
      evidence-based guidelines for the management of minimal, mild or moderate head
      injuries. Since then, considerable new evidence has emerged on the clinical use
      of these guidelines and on the radiation risks associated with computer
      tomographic (CT) examinations. The SNC has recently published updated
      Scandinavian guidelines. Here we present the Norwegian version of the updated
      guidelines with emphasis on the professional recommendations and the reasons the
      new guidelines were necessary, plus comments from the Norwegian authors.MATERIALS
      AND METHODS A task force appointed by the SNC compiled recommendations based on a
      systematic, evidence-based review. These recommendations were revised through
      consensus in the SNC and through consultation with relevant clinical
      experts.RESULTS A blood test of the brain injury biomarker S100B is for the first
      time recommended as an initial diagnostic measure for mild head injury patients
      with low risk. Of these patients, CT examination is only recommended for those
      who show a pathologically elevated S100B. CT examination is still the recommended
      routine for moderate head injury patients and for mild head injury patients with
      medium to high risk. An updated information sheet on head injuries has also been
      compiled for patients and their relatives.CONCLUSION The SNC recommends the
      implementation of these guidelines in Norway. 

PMID- 24287848
TI  - Construction of transplastomic lettuce (Lactuca sativa) dominantly producing
      astaxanthin fatty acid esters and detailed chemical analysis of generated
      carotenoids.
AB  - The plastid genome of lettuce (Lactuca sativa L.) cv. Berkeley was site
      specifically modified with the addition of three transgenes, which encoded
      beta,beta-carotenoid 3,3'-hydroxylase (CrtZ) and beta,beta-carotenoid 4,4'
      ketolase (4,4'-oxygenase; CrtW) from a marine bacterium Brevundimonas sp. strain
      SD212, and isopentenyl diphosphate isomerase from a marine bacterium Paracoccus
      sp. strain N81106. Constructed transplastomic lettuce plants were able to grow on
      soil at a growth rate similar to that of non-transformed lettuce cv. Berkeley and
      generate flowers and seeds. The germination ratio of the lettuce transformants
      (T0) (98.8%) was higher than that of non-transformed lettuce (93.1 %). The
      transplastomic lettuce (T1) leaves produced the astaxanthin fatty acid (myristate
      or palmitate) diester (49.2% of total carotenoids), astaxanthin monoester
      (18.2%), and the free forms of astaxanthin (10.0%) and the other ketocarotenoids
      (17.5%), which indicated that artificial ketocarotenoids corresponded to 94.9% of
      total carotenoids (230 MUg/g fresh weight). Native carotenoids were there
      lactucaxanthin (3.8%) and lutein (1.3 %) only. This is the first report to
      structurally identify the astaxanthin esters biosynthesized in transgenic or
      transplastomic plants producing astaxanthin. The singlet oxygen-quenching
      activity of the total carotenoids extracted from the transplastomic leaves was
      similar to that of astaxanthin (mostly esterified) from the green algae
      Haematococcus pluvialis.

PMID- 24287849
TI  - Effects of habitual anger on employees' behavior during organizational change.
AB  - Organizational change is a particularly emotional event for those being
      confronted with it. Anger is a frequently experienced emotion under these
      conditions. This study analyses the influence of employees' habitual anger
      reactions on their reported behavior during organizational change. It was
      explored whether anger reactions conducive to recovering or increasing individual
      well-being will enhance the likelihood of functional change behavior.
      Dysfunctional regulation strategies in terms of individual well-being are
      expected to decrease the likelihood of functional change behavior-mediated by the
      commitment to change. Four hundred and twelve employees of different
      organizations in Luxembourg undergoing organizational change participated in the
      study. Findings indicate that the anger regulation strategy venting, and humor
      increase the likelihood of deviant resistance to change. Downplaying the
      incident's negative impact and feedback increase the likelihood of active support
      for change. The mediating effect of commitment to change has been found for humor
      and submission. The empirical findings suggest that a differentiated
      conceptualization of resistance to change is required. Specific implications for
      practical change management and for future research are discussed. 

PMID- 24287851
TI  - The changing epidemiology of Kunjin virus in Australia.
AB  - West Nile virus (WNV) is a mosquito-borne virus responsible for outbreaks of
      viral encephalitis in humans and horses, with particularly virulent strains
      causing recent outbreaks of disease in Eastern Europe, the Middle East and North
      America. A strain of WNV, Kunjin (WNVKUN), is endemic in northern Australia and
      infection with this virus is generally asymptomatic. However in early 2011, an
      unprecedented outbreak of encephalitis in horses occurred in south-eastern
      Australia, resulting in mortality in approximately 10%-15% of infected horses. A
      WNV-like virus (WNVNSW2011) was isolated and found to be most closely related to
      the indigenous WNVKUN, rather than other exotic WNV strains. Furthermore, at
      least two amino acid changes associated with increased virulence of the North
      American New York 99 strain (WNVNY99) compared to the prototype WNVKUN were
      present in the WNVNSW2011 sequence. This review summarizes our current
      understanding of WNVKUN and how the epidemiology and ecology of this virus has
      changed. Analysis of virulence determinants of contemporary WNVKUN isolates will
      provide clues on where virulent strains have emerged in Australia. A better
      understanding of the changing ecology and epidemiology associated with the
      emergence of virulent strains is essential to prepare for future outbreaks of WNV
      disease in Australia. 

PMID- 24287850
TI  - Escherichia coli in Europe: an overview.
AB  - Escherichia coli remains one of the most frequent causes of several common
      bacterial infections in humans and animals. E. coli is the prominent cause of
      enteritis, urinary tract infection, septicaemia and other clinical infections,
      such as neonatal meningitis. E. coli is also prominently associated with
      diarrhoea in pet and farm animals. The therapeutic treatment of E. coli
      infections is threatened by the emergence of antimicrobial resistance. The
      prevalence of multidrug-resistant E. coli strains is increasing worldwide
      principally due to the spread of mobile genetic elements, such as plasmids. The
      rise of multidrug-resistant strains of E. coli also occurs in Europe. Therefore,
      the spread of resistance in E. coli is an increasing public health concern in
      European countries. This paper summarizes the current status of E. coli strains
      clinically relevant in European countries. Furthermore, therapeutic interventions
      and strategies to prevent and control infections are presented and discussed. The
      article also provides an overview of the current knowledge concerning promising
      alternative therapies against E. coli diseases. 

PMID- 24287852
TI  - Indoor and outdoor monitoring of volatile organic compounds in school buildings:
      indicators based on health risk assessment to single out critical issues.
AB  - Children are more sensitive to pollutants than adults and yet they spend large
      amounts of time in school environments where they are exposed to unknown levels
      of indoor pollutants. This study investigated the concentrations of the most
      abundant volatile organic compounds (VOCs) in eight naturally ventilated school
      buildings in Italy. The schools were chosen to include areas with different
      urbanization and traffic density characteristics in order to gather a more
      diverse picture of exposure risks in the different areas of the city. VOCs were
      sampled for one week in the presence/absence of pupils using diffusive samplers
      suitable for thermal desorption inside three classrooms at each school. The
      samples were then analyzed with thermal desorption-gas chromatography-mass
      spectrometry (TD-GC-MS). In addition, outdoor measurements were carried out in
      the yard at each school. VOC identification and quantification, and
      indoor/outdoor concentration plots were used to identify pollutant sources. While
      some classrooms were found to have very low VOC levels, others had a significant
      indoor contribution or a prevalent outdoor contribution. High concentrations of
      terpenes were found in all monitored classrooms: a-pinene and limonene were in
      the range of 6.55-34.18 ug/m3 and 11.11-25.42 ug/m3 respectively. Outdoor
      concentrations were lower than indoors for each monitored school. Indicators
      based on health risk assessment for chronic health effects associated with VOCs
      (either carcinogenic or non-carcinogenic) were proposed to rank sites according
      to their hazard level. 

PMID- 24287853
TI  - Foodborne Campylobacter: infections, metabolism, pathogenesis and reservoirs.
AB  - Campylobacter species are a leading cause of bacterial-derived foodborne
      illnesses worldwide. The emergence of this bacterial group as a significant
      causative agent of human disease and their propensity to carry antibiotic
      resistance elements that allows them to resist antibacterial therapy make them a
      serious public health threat. Campylobacter jejuni and Campylobacter coli are
      considered to be the most important enteropathogens of this genus and their
      ability to colonize and survive in a wide variety of animal species and habitats
      make them extremely difficult to control. This article reviews the historical and
      emerging importance of this bacterial group and addresses aspects of the human
      infections they cause, their metabolism and pathogenesis, and their natural
      reservoirs in order to address the need for appropriate food safety regulations
      and interventions. 

PMID- 24287854
TI  - Factor structure of early smoking experiences and associations with smoking
      behavior: valence or sensitivity model?
AB  - The Early Smoking Experience (ESE) questionnaire is the most widely used
      questionnaire to assess initial subjective experiences of cigarette smoking.
      However, its factor structure is not clearly defined and can be perceived from
      two main standpoints: valence, or positive and negative experiences, and
      sensitivity to nicotine. This article explores the ESE's factor structure and
      determines which standpoint was more relevant. It compares two groups of young
      Swiss men (German- and French-speaking). We examined baseline data on 3,368
      tobacco users from a representative sample in the ongoing Cohort Study on
      Substance Use Risk Factors (C-SURF). ESE, continued tobacco use, weekly smoking
      and nicotine dependence were assessed. Exploratory structural equation modeling
      (ESEM) and structural equation modeling (SEM) were performed. ESEM clearly
      distinguished positive experiences from negative experiences, but negative
      experiences were divided in experiences related to dizziness and experiences
      related to irritations. SEM underlined the reinforcing effects of positive
      experiences, but also of experiences related to dizziness on nicotine dependence
      and weekly smoking. The best ESE structure for predictive accuracy of experiences
      on smoking behavior was a compromise between the valence and sensitivity
      standpoints, which showed clinical relevance. 

PMID- 24287855
TI  - Assessing weather effects on dengue disease in Malaysia.
AB  - The number of dengue cases has been increasing on a global level in recent years,
      and particularly so in Malaysia, yet little is known about the effects of weather
      for identifying the short-term risk of dengue for the population. The aim of this
      paper is to estimate the weather effects on dengue disease accounting for non
      linear temporal effects in Selangor, Kuala Lumpur and Putrajaya, Malaysia, from
      2008 to 2010. We selected the weather parameters with a Poisson generalized
      additive model, and then assessed the effects of minimum temperature, bi-weekly
      accumulated rainfall and wind speed on dengue cases using a distributed non
      linear lag model while adjusting for trend, day-of-week and week of the year. We
      found that the relative risk of dengue cases is positively associated with
      increased minimum temperature at a cumulative percentage change of 11.92% (95%
      CI: 4.41-32.19), from 25.4  degrees C to 26.5  degrees C, with the highest effect
      delayed by 51 days. Increasing bi-weekly accumulated rainfall had a positively
      strong effect on dengue cases at a cumulative percentage change of 21.45% (95%
      CI: 8.96, 51.37), from 215 mm to 302 mm, with the highest effect delayed by 26-28
      days. The wind speed is negatively associated with dengue cases. The estimated
      lagged effects can be adapted in the dengue early warning system to assist in
      vector control and prevention plan. 

PMID- 24287856
TI  - Mouse models of mutations and variations in autism spectrum disorder-associated
      genes: mice expressing Caps2/Cadps2 copy number and alternative splicing
      variants.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by
      disturbances in interpersonal relationships and behavior. Although the prevalence
      of autism is high, effective treatments have not yet been identified. Recently,
      genome-wide association studies have identified many mutations or variations
      associated with ASD risk on many chromosome loci and genes. Identification of the
      biological roles of these mutations or variations is necessary to identify the
      mechanisms underlying ASD pathogenesis and to develop clinical treatments. At
      present, mice harboring genetic modifications of ASD-associated gene candidates
      are the best animal models to analyze hereditary factors involved in autism. In
      this report, the biological significance of ASD-associated genes is discussed by
      examining the phenotypes of mouse models with ASD-associated mutations or
      variations in mouse homologs, with a focus on mice harboring genetic
      modifications of the Caps2/Cadps2 (Ca2+-dependent activator protein for secretion
      2) gene. 

PMID- 24287857
TI  - Issues to consider when measuring and applying socioeconomic position
      quantitatively in immigrant health research.
AB  - The relationship between migration and health is complex, yet, immigrant-related
      inequalities in health are largely influenced by socioeconomic position. Drawing
      upon previous findings, this paper discusses issues to consider when measuring
      and applying socioeconomic position in quantitative immigrant health research.
      When measuring socioeconomic position, it is important to be aware of four
      aspects: (1) there is a lack of clarity about how socioeconomic position should
      be measured; (2) different types of socioeconomic position may be relevant to
      immigrants compared with the native-born population; (3) choices of measures of
      socioeconomic position in quantitative analyses often rely on data availability;
      and (4) different measures of socioeconomic position have different effects in
      population groups. Therefore, caution should be used in the collection,
      presentation, analyses, and interpretation of data and researchers need to
      display their proposed conceptual models and data limitations as well as apply
      different approaches for analyses. 

PMID- 24287858
TI  - Vector contact rates on Eastern bluebird nestlings do not indicate West Nile
      virus transmission in Henrico County, Virginia, USA.
AB  - Sensitive indicators of spatial and temporal variation in vector-host contact
      rates are critical to understanding the transmission and eventual prevention of
      arboviruses such as West Nile virus (WNV). Monitoring vector contact rates on
      particularly susceptible and perhaps more exposed avian nestlings may provide an
      advanced indication of local WNV amplification. To test this hypothesis we
      monitored WNV infection and vector contact rates among nestlings occupying nest
      boxes (primarily Eastern bluebirds; Sialia sialis, Turdidae) across Henrico
      County, Virginia, USA, from May to August 2012. Observed host-seeking rates were
      temporally variable and associated with absolute vector and host abundances.
      Despite substantial effort to monitor WNV among nestlings and mosquitoes, we did
      not detect the presence of WNV in these populations. Generally low vector
      nestling host contact rates combined with the negative WNV infection data suggest
      that monitoring transmission parameters among nestling Eastern bluebirds in
      Henrico County, Virginia, USA may not be a sensitive indicator of WNV activity. 

PMID- 24287859
TI  - Monitoring street-level spatial-temporal variations of carbon monoxide in urban
      settings using a wireless sensor network (WSN) framework.
AB  - Air pollution has become a severe environmental problem due to urbanization and
      heavy traffic. Monitoring street-level air quality is an important issue, but
      most official monitoring stations are installed to monitor large-scale air
      quality conditions, and their limited spatial resolution cannot reflect the
      detailed variations in air quality that may be induced by traffic jams. By
      deploying wireless sensors on crossroads and main roads, this study established a
      pilot framework for a wireless sensor network (WSN)-based real-time monitoring
      system to understand street-level spatial-temporal changes of carbon monoxide
      (CO) in urban settings. The system consists of two major components. The first
      component is the deployment of wireless sensors. We deployed 44 sensor nodes, 40
      transmitter nodes and four gateway nodes in this study. Each sensor node includes
      a signal processing module, a CO sensor and a wireless communication module. In
      order to capture realistic human exposure to traffic pollutants, all sensors were
      deployed at a height of 1.5 m on lampposts and traffic signs. The study area
      covers a total length of 1.5 km of Keelung Road in Taipei City. The other
      component is a map-based monitoring platform for sensor data visualization and
      manipulation in time and space. Using intensive real-time street-level monitoring
      framework, we compared the spatial-temporal patterns of air pollution in
      different time periods. Our results capture four CO concentration peaks
      throughout the day at the location, which was located along an arterial and
      nearby traffic sign. The hourly average could reach 5.3 ppm from 5:00 pm to 7:00
      pm due to the traffic congestion. The proposed WSN-based framework captures
      detailed ground information and potential risk of human exposure to traffic
      related air pollution. It also provides street-level insights into real-time
      monitoring for further early warning of air pollution and urban environmental
      management. 

PMID- 24287860
TI  - The influence of domestic overload on the association between job strain and
      ambulatory blood pressure among female nursing workers.
AB  - Evidence suggests that the workplace plays an important etiologic role in blood
      pressure (BP) alterations. Associations in female samples are controversial, and
      the domestic environment is hypothesized to be an important factor in this
      relationship. This study assessed the association between job strain and BP
      within a sample of female nursing workers, considering the potential role of
      domestic overload. A cross-sectional study was conducted in a group of 175
      daytime workers who wore an ambulatory BP monitor for 24 h during a working day.
      Mean systolic and diastolic BP were calculated. Job strain was evaluated using
      the Demand-Control Model. Domestic overload was based on the level of
      responsibility in relation to four household tasks and on the number of
      beneficiaries. After adjustments no significant association between high job
      strain and BP was detected. Stratified analyses revealed that women exposed to
      both domestic overload and high job strain had higher systolic BP at home. These
      results indicate a possible interaction between domestic overload and job strain
      on BP levels and revealed the importance of domestic work, which is rarely
      considered in studies of female workers. 

PMID- 24287861
TI  - Impact and cost-effectiveness of a comprehensive Schistosomiasis japonica control
      program in the Poyang Lake region of China.
AB  - Schistosomiasis japonica remains a significant public-health problem in China.
      This study evaluated cost-effectiveness of a comprehensive schistosomiasis
      control program (2003-2006). The comprehensive control program was implemented in
      Zhangjia and Jianwu (cases); while standard interventions continued in Koutou and
      Xiajia (controls). Incurred costs were documented and the schistosomiasis
      comprehensive impact index (SCI) and cost-effectiveness ratio (Comprehensive
      Control Program Cost/SCI) were applied. In 2003, prevalence of Schistosoma
      japonicum infection was 11.3% (Zhangjia), 6.7% (Jianwu), 6.5% (Koutou), and 8.0%
      (Xiajia). In 2006, the comprehensive control program in Zhangjia and Jianwu
      reduced infection to 1.6% and 0.6%, respectively; while Koutou and Xiajia had a
      schistosomiasis prevalence of 3.2% and 13.0%, respectively. The year-by-year SCIs
      in Zhangjia were 0.28, 105.25, and 47.58, with an overall increase in cost
      effectiveness ratio of 374.9%-544.8%. The SCIs in Jianwu were 16.21, 52.95, and
      149.58, with increase in cost-effectiveness of 226.7%-1,149.4%. Investment in
      Koutou and Xiajia remained static (US$10,000 unit cost). The comprehensive
      control program implemented in the two case villages reduced median prevalence of
      schistosomiasis 8.5-fold. Further, the cost effectiveness ratio demonstrated that
      the comprehensive control program was 170% (Zhangjia) and 922.7% (Jianwu) more
      cost-effective. This work clearly shows the improvements in both cost and disease
      prevention effectiveness that a comprehensive control program-approach has on
      schistosomiasis infection prevalence. 

PMID- 24287862
TI  - Impact of traumatic dental injury on the quality of life of Brazilian preschool
      children.
AB  - This study aimed to assess the impact of traumatic dental injury (TDI) on the
      quality of life of preschoolers and their families. A cross-sectional study was
      carried out, with a sample of 814 children, aged three to five years old, in
      Campina Grande, Brazil. Parents/caregivers were asked to complete the Brazilian
      Early Childhood Oral Health Impact Scale and a questionnaire on socio-demographic
      data. Oral examinations of the children were performed by three previously
      calibrated dentists. Bivariate and multiple Poisson regression analyses were
      performed (alpha = 5%). The prevalence of negative impact from oral conditions on
      quality of life was 31.1% among the children and 24.7% among the families. TDI
      was not associated with a negative impact on quality of life. Parent/caregiver's
      assessment of the child's oral health (PR = 1.210; 95% CI: 1.027-1.426) and
      history of toothache (PR = 4.997; 95% CI: 2.943-8.493) remained in the final
      model for the child section, whereas only a history of toothache (PR = 2.791; 95%
      CI: 1.801-4.325) remained in the final model for the family section. TDI exerted
      no negative impact on quality of life in the present sample. A history of
      toothache was the only variable associated with a negative impact on the quality
      of life of the preschoolers and their families. 

PMID- 24287864
TI  - Crossing the telemedicine chasm: have the U.S. barriers to widespread adoption of
      telemedicine been significantly reduced?
AB  - Barriers have challenged widespread telemedicine adoption by health care
      organizations for 40 years. These barriers have been technological, financial,
      and legal and have also involved business strategy and human resources. The
      article canvasses recent trends-events and activities in each of these areas as
      well as US health reform activities that might help to break down these barriers.
      The key to telemedicine success in the future is to view it as an integral part
      of health care services and not as a stand-alone project. Telemedicine must move
      from experimental and separate to integrated and equivalent to other health
      services within health care organizations. Furthermore, telemedicine serves as
      vital connective tissue for expanding health care organization networks. 

PMID- 24287865
TI  - Mucosal immunology: Bacteria get T(Reg) cells into shape.

PMID- 24287866
TI  - Enhanced visible-light photocatalytic activity of plasmonic Ag and graphene co
      modified Bi2WO6 nanosheets.
AB  - Photocatalytic degradation of pollutants in water has received much attention due
      to increasing environmental problems. In this study, a visible-light-driven
      plasmonic silver-graphene-bismuth tungsten (Ag-G-Bi2WO6) composite photocatalyst
      was prepared. Firstly, the graphite oxide (GO)-Bi2WO6 composite was prepared
      using a hydrothermal process, followed by a chemical reduction process using
      ethyl glycol (EG) as the reducing agent to form the G-Bi2WO6 composite. Then, Ag
      nanoparticles (NPs) were loaded onto the G-Bi2WO6 composite using a simple
      photochemical reduction process under xenon lamp irradiation to form the Ag-G
      Bi2WO6 composite. The prepared samples were characterized using X-ray
      diffraction, transmission electron microscopy, nitrogen adsorption-desorption
      isotherm, UV-visible diffuse reflectance spectroscopy and electrochemical
      impedance spectroscopy. The photocatalytic activities of the prepared samples
      were evaluated by the photocatalytic degradation of rhodamine B (RhB) aqueous
      solution at ambient temperature under visible-light irradiation. The results
      showed that the photocatalytic activity of Bi2WO6 was significantly enhanced by
      the loading of Ag and graphene. The high photocatalytic activity is attributed
      predominantly to the hybridization of the surface plasmonic resonance (SPR)
      effect of Ag NPs and the specific electronics effect of graphene on the Bi2WO6
      surface, thus enhancing the generation and separation of photogenerated charge
      carriers of Bi2WO6. Meanwhile, the excellent adsorption capacity of graphene also
      contributes to the enhancement of photocatalytic activity. This work highlights
      the design and preparation of new photocatalysts using plasmonic Ag and graphene
      as cocatalyst. 

PMID- 24287863
TI  - Occupational pesticide exposures and respiratory health.
AB  - Pesticides have been widely used to control pest and pest-related diseases in
      agriculture, fishery, forestry and the food industry. In this review, we identify
      a number of respiratory symptoms and diseases that have been associated with
      occupational pesticide exposures. Impaired lung function has also been observed
      among people occupationally exposed to pesticides. There was strong evidence for
      an association between occupational pesticide exposure and asthma, especially in
      agricultural occupations. In addition, we found suggestive evidence for a link
      between occupational pesticide exposure and chronic bronchitis or COPD. There was
      inconclusive evidence for the association between occupational pesticide exposure
      and lung cancer. Better control of pesticide uses and enforcement of safety
      behaviors, such as using personal protection equipment (PPE) in the workplace,
      are critical for reducing the risk of developing pesticide-related symptoms and
      diseases. Educational training programs focusing on basic safety precautions and
      proper uses of personal protection equipment (PPE) are possible interventions
      that could be used to control the respiratory diseases associated with pesticide
      exposure in occupational setting. 

PMID- 24287867
TI  - Downregulation of c-Kit/MITF-M in graying hair of juvenile poliosis.

PMID- 24287868
TI  - Localisation of the SMC loading complex Nipbl/Mau2 during mammalian meiotic
      prophase I.
AB  - Evidence from lower eukaryotes suggests that the chromosomal associations of all
      the structural maintenance of chromosome (SMC) complexes, cohesin, condensin and
      Smc5/6, are influenced by the Nipbl/Mau2 heterodimer. Whether this function is
      conserved in mammals is currently not known. During mammalian meiosis, very
      different localisation patterns have been reported for the SMC complexes, and the
      localisation of Nipbl/Mau2 has just recently started to be investigated. Here, we
      show that Nipbl/Mau2 binds on chromosomal axes from zygotene to mid-pachytene in
      germ cells of both sexes. In spermatocytes, Nipbl/Mau2 then relocalises to
      chromocenters, whereas in oocytes it remains bound to chromosomal axes throughout
      prophase to dictyate arrest. The localisation pattern of Nipbl/Mau2, together
      with those seen for cohesin, condensin and Smc5/6 subunits, is consistent with a
      role as a loading factor for cohesin and condensin I, but not for Smc5/6. We also
      demonstrate that Nipbl/Mau2 localises next to Rad51 and gammaH2AX foci. NIPBL
      gene deficiencies are associated with the Cornelia de Lange syndrome in humans,
      and we find that haploinsufficiency of the orthologous mouse gene results in an
      altered distribution of double-strand breaks marked by gammaH2AX during prophase
      I. However, this is insufficient to result in major meiotic malfunctions, and the
      chromosomal associations of the synaptonemal complex proteins and the three SMC
      complexes appear cytologically indistinguishable in wild-type and Nipbl (+/-)
      spermatocytes. 

PMID- 24287869
TI  - Normal patterns of 18F-FDG appendiceal uptake in children.
AB  - BACKGROUND: Prior to interpreting PET/CT, it is crucial to understand the normal
      biodistribution of fluorodeoxyglucose (FDG). It is also important to realize that
      the normal biodistribution can vary between adults and children. Although many
      studies have defined normal patterns of pediatric FDG uptake in structures like
      the thymus, brown fat and bone marrow, patterns of normal pediatric bowel
      activity, specifically uptake within the appendix, have not been well described.
      Active lymphoid tissue has increased FDG uptake when compared with inactive
      tissue. Since children have more active lymphoid tissue than adults, and because
      the appendix contains aggregated lymphoid tissue, we postulated that appendiceal
      uptake may be increased in pediatric patients. OBJECTIVE: To define the normal
      level of appendiceal FDG activity in children by evaluating a series of
      consecutive FDG PET/CT scans performed for other indications. MATERIALS AND
      METHODS: After obtaining IRB approval, we retrospectively reviewed 128
      consecutive whole-body pediatric FDG PET/CT examinations obtained for a variety
      of clinical indications. CT scans on which the appendix could not be visualized
      were excluded from analysis. CT scans on which the appendix could be visualized
      were evaluated for underlying appendiceal pathology. Studies with appendiceal or
      periappendiceal pathology by CT criteria were excluded. A region of interest
      (ROI) was placed over a portion of each appendix and appendiceal maximum
      standardized uptake value (SUVmax) was calculated. If an adjacent loop of bowel
      activity interfered with accurate measurements of the appendix SUVmax, the scan
      was excluded from the analysis. A chart review was performed on patients with
      elevated appendiceal SUVmax values to ensure that the patients did not have
      clinical symptomatology suggestive of acute appendicitis. When the appendix or a
      portion of the appendix could be visualized and accurately measured, the SUVmax
      was determined. SUVmax of the appendix was compared to the SUVmax of normal liver
      and ratios were recorded. RESULTS: A total of 128 scans were reviewed, patient
      ages 1 month to 21 years (mean age: 11.6 years). Thirty-one scans were excluded
      because of inability to visualize the appendix on CT. No scans were excluded for
      appendiceal/periappendiceal pathology on CT or chart review. No scans had to be
      excluded for inability to obtain an accurate SUVmax measurement because
      measurements were calculated on portions of the appendix separate from adjacent
      bowel using small ROIs. Maximum appendiceal SUVs ranged from 0.5 to 9.4 (mean:
      2.2) with an appendix-to-liver background ratio ranging from 0.3 to 3.1 (mean:
      1.1). CONCLUSION: FDG uptake in the appendix is typically similar to that of
      background activity. However, slight variations in appendiceal FDG uptake do
      occur, which should not be misinterpreted as pathological.

PMID- 24287870
TI  - Roseomonas sediminicola sp. nov., isolated from fresh water.
AB  - A Gram-stain negative, strictly aerobic, non-motile, non-spore-forming, and rod
      shaped bacterial strain designated FW-3(T) was isolated from fresh water and its
      taxonomic position was investigated by using a polyphasic approach. Strain FW
      3(T) was found to grow at 10-37  degrees C and at pH 7.0 in the absence of NaCl
      on nutrient agar. On the basis of 16S rRNA gene sequence similarity, strain FW
      3(T) was shown to belong to the family Acetobacteraceae and to be related to
      Roseomonas lacus TH-G33(T) (97.2 % sequence similarity) and Roseomonas terrae DS
      48(T) (96.4 %). The G+C content of the genomic DNA was determined to be 68.0 %.
      The major menaquinone was determined to be Q-10 and the major fatty acids were
      identified as summed feature 7 (comprising C18:1 omega9c/omega12t/omega7c as
      defined by the MIDI system; 55.4 %), and C18:1 2OH (29.8 %). DNA and
      chemotaxonomic data supported the affiliation of strain FW-3(T) to the genus
      Roseomonas. Strain FW-3(T) could be differentiated genotypically and
      phenotypically from the recognized species of the genus Roseomonas. The novel
      isolate therefore represents a novel species, for which the name Roseomonas
      sediminicola sp. nov. is proposed, with the type strain FW-3(T) (=KACC 16616(T) =
      JCM 18210(T)). 

PMID- 24287872
TI  - Reactivity of a fac-ReCl(alpha-diimine)(CO)3 complex with an NAD+ model ligand
      toward CO2 reduction.
AB  - The reactivity of a rhenium complex containing an NAD(+) model ligand was
      examined toward photochemical formation of the corresponding NADH-like dihydro
      form of the complex and electrochemical CO2 reduction. The hydricity of the NADH
      like complex was estimated by a thermodynamic cycle and reaction with Ph3C(+). 

PMID- 24287871
TI  - PPARgamma modulates vascular smooth muscle cell phenotype via a protein kinase G
      dependent pathway and reduces neointimal hyperplasia after vascular injury.
AB  - Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to
      vascular injury such as angioplasty. Protein kinase G (PKG) has an important role
      in the process of VSMC phenotype switching. In this study, we examined whether
      rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist,
      could modulate VSMC phenotype through the PKG pathway to reduce neointimal
      hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone
      inhibited the phenotype change of VSMCs from a contractile to a synthetic form.
      The platelet-derived growth factor (PDGF)-induced reduction of PKG level was
      reversed by rosiglitazone treatment, resulting in increased PKG activity. This
      increased activity of PKG resulted in phosphorylation of vasodilator-stimulated
      phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs.
      Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or
      cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that
      rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the
      PKG promoter showed that the activation of PKG by rosiglitazone was mediated by
      the increased binding of Sp1 on the promoter region of PKG. In vivo experiments
      showed that rosiglitazone significantly inhibited neointimal formation after
      balloon injury. Immunohistochemistry staining for calponin and thrombospondin
      showed that this effect of rosiglitazone was mediated by modulating VSMC
      phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of
      VSMC phenotype, which is regulated by PKG. This activation of PKG by
      rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These
      results provide important mechanistic insight into the cardiovascular-protective
      effect of PPARgamma. 

PMID- 24287873
TI  - The effect of regioisomerism on the coordination chemistry and CEST properties of
      lanthanide(III) NB-DOTA-tetraamide chelates.
AB  - Chemical exchange saturation transfer (CEST) offers many advantages as a method
      of generating contrast in magnetic resonance images. However, many of the
      exogenous agents currently under investigation suffer from detection limits that
      are still somewhat short of what can be achieved with more traditional Gd(3+)
      agents. To remedy this limitation we have undertaken an investigation of Ln(3+)
      DOTA-tetraamide chelates (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid) that have unusually rigid ligand structures: the nitrobenzyl
      derivatives of DOTA-tetraamides with (2-phenylethyl)amide substituents. In this
      report we examine the effect of incorporating hydrophobic amide substituents on
      water exchange and CEST. The ligand systems chosen afforded a total of three CEST
      active isomeric square antiprismatic chelates; each of these chelates was found
      to have different water exchange and CEST characteristics. The position of a
      nitrobenzyl substituent on the macrocyclic ring strongly influenced the way in
      which the chelate and Ln(3+) coordination cage distorted. These differential
      distortions were found to affect the rate of water proton exchange in the
      chelates. But, by far the greatest effect arose from altering the position of the
      hydrophobic amide substituent, which, when forced upwards around the water
      binding site, caused a substantial reduction in the rate of water proton
      exchange. Such slow water proton exchange afforded a chelate that was 4.5 times
      more effective as a CEST agent than its isomeric counterparts in dry acetonitrile
      and at low temperatures and very low presaturation powers.

PMID- 24287875
TI  - Could serum nitrate and nitrite levels possibly predict hepatorenal syndrome in
      hepatitis C virus-related liver cirrhosis?
AB  - PURPOSE: This study aimed to determine whether serum levels of nitric oxide
      metabolites (nitrates and nitrites) correlate with renal dysfunction in patients
      with liver cirrhosis and, moreover, to assess nitric oxide metabolite (NOx) power
      for predicting hepatorenal syndrome (HRS) in such patients. METHODS: Among
      patients admitted to the Tropical Medicine Department, Ain Shams University
      Hospital, a total of 60 patients with chronic hepatitis C-related liver cirrhosis
      were included in this study. Patients were divided into three groups. Group I
      included 20 patients with compensated liver cirrhosis (CLC). Group II included 20
      patients with decompensated liver cirrhosis (DLC). Group III included 20 patients
      with decompensated liver cirrhosis and HRS. Twenty healthy subjects with no
      clinical or laboratory evidence of liver disease were enrolled as a control group
      (group IV). RESULTS: Patients with HRS had a higher mean nitrite levels followed
      by DLC, then CLC, and then controls. The sensitivity and specificity of NO
      metabolites (nitrites) were 100 % and 93.3 %, respectively, with accuracy of 95 %
      at cutoff value of 387 MUmol/L for diagnosing patients with HRS. There was a
      highly significant statistical difference between patients positive and negative
      for nitrites as regards renal profile (p = 0.000). CONCLUSION: A strong relation
      between nitrite cutoff value and renal dysfunction in liver cirrhosis has been
      found. Also, patients with HRS had higher mean serum nitrite levels than
      decompensated liver cirrhosis or compensated liver cirrhosis, raising the
      possibility of using nitrate and nitrite levels as a predictor for HRS in HCV
      related liver cirrhosis.

PMID- 24287874
TI  - Mitochondria are the primary target in the induction of apoptosis by chiral
      ruthenium(II) polypyridyl complexes in cancer cells.
AB  - A series of novel chiral ruthenium(II) polypyridyl complexes (Delta-Ru1, Lambda
      Ru1, Delta-Ru2, Lambda-Ru2, Delta-Ru3, Lambda-Ru3) were synthesized and evaluated
      to determine their antiproliferative activities. Colocalization, inductively
      coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay studies showed that these ruthenium(II)
      complexes accumulated preferentially in the mitochondria and exhibited
      cytotoxicity against various cancer cells in vitro. The complex Delta-Ru1 is of
      particular interest because it was found to have half-maximal inhibitory
      concentrations comparable to those of cisplatin and better activity than
      cisplatin against a cisplatin-resistant cell line, A549-CP/R. Delta-Ru1 induced
      alterations in the mitochondrial membrane potential and triggered intrinsic
      mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of
      Bcl-2 family members and the activation of caspases. Taken together, these data
      suggest that Delta-Ru1 may be a novel mitochondria-targeting anticancer agent. 

PMID- 24287876
TI  - Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth,
      Survival, and Invasion Through Inhibition of NFkappaB Signaling.
AB  - Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in
      South American medicine. A recent study showed that Pao extract repressed
      androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao
      extract asserts its anticancer effects on metastatic castration-resistant
      prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a
      dose- and time-dependent manner, through induction of apoptosis and cell cycle
      arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and
      repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the
      upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL, and
      XIAP expression, which were associated with the cleavage of PARP protein.
      Moreover, Pao extract treatment blocked PC3 cell migration and invasion.
      Mechanistically, Pao extract suppressed phosphorylation levels of AKT and
      NFkappaB/p65, NFkappaB DNA binding activity, and luciferase reporter activity.
      Pao inhibited TNFalpha-induced relocation of NFkappaB/p65 to the nucleus,
      NFkappaB/p65 transcription activity, and MMP9 activity as shown by zymography.
      Consistently, NFkappaB/p65 downstream targets involved in proliferation (Cyclin
      D1), survival (Bcl-2, Bcl-xL, and XIAP), and metastasis (VEGFa, MMP9, and
      GROalpha/CXCL1) were also downregulated by Pao extract. Finally, forced
      expression of NFkappaB/p65 reversed the growth inhibitory effect of Pao extract.
      Overall, Pao extract induced cell growth arrest, apoptosis, partially through
      inhibiting NFkappaB activation in prostate cancer cells. These data suggest that
      Pao extract may be beneficial for protection against CRPC. 

PMID- 24287877
TI  - Integrating porphyrin nanoparticles into a 2D graphene matrix for free-standing
      nanohybrid films with enhanced visible-light photocatalytic activity.
AB  - Organic nanostructures in terms of porphyrin building blocks have shown great
      potential in visible-light photocatalytic applications because of their optical,
      electrical, and catalytic properties. Graphenes are known to provide a high
      quality two-dimensional (2D) support for inorganic semiconductor nanostructures
      to increase the adsorption capability of the photocatalysts and an electron
      transfer medium with attractive potential to enhance photogenerated charge
      separation. A combination of porphyrin nanostructures with graphene sheets,
      particularly in the form of free-standing films, is highly desirable due to its
      photocatalysing feasibility and convenience. Toward this aim, we demonstrate a
      facile method to integrate porphyrin (meso-tetra(p-hydroxyphenyl)porphyrin, p
      THPP) nanoparticles (NPs) into macroscopic graphene (reduced graphene oxide, rGO)
      films through vacuum filtration of the co-colloids of graphene oxide (GO) and p
      THPP nanoparticles (NPs) followed by gaseous reduction. The obtained p-THPP/rGO
      nanohybrid film exhibits enhanced visible-light photocatalytic activity compared
      to each moiety of the hybrid, and this photocatalyst can be easily separated and
      recycled for successive use with excellent stability. The results show that this
      facile fabrication of the p-THPP/rGO nanohybrid film makes it available for high
      performance optoelectronic applications, as well as for device integration. 

PMID- 24287878
TI  - Impacts of autistic behaviors, emotional and behavioral problems on parenting
      stress in caregivers of children with autism.
AB  - This study examined the effects of autistic behaviors and individual emotional
      and behavioral problems on parenting stress in caregivers of children with
      autism. Caregivers were interviewed with the Childhood Autism Rating Scale and
      completed the Strength and Difficulties Questionnaire and the Parenting Stress
      Index Short Form. Results revealed that caregivers of children with mild/moderate
      autistic behavior problems perceived lower parenting stress than did those of
      children with no or severe problems. In addition, prosocial behaviors and conduct
      problems respectively predicted stress in the parent-child relationship and child
      related stress. The findings can provide guidance in evaluations and
      interventions with a focus on mitigating parenting stress in caregivers of
      children with autism. 

PMID- 24287879
TI  - Broadband behavior rating scales as screeners for autism?
AB  - In order to start providing important early intervention services to preschoolers
      and toddlers with autism, those children first need to be identified. Despite the
      availability of specialized autism assessment instruments, there is a need for
      effective screeners at the early childhood level. Three broadband behavior rating
      scales were evaluated in this study to determine if any of the scales on the
      instruments could adequately distinguish between children with autism from other
      clinically referred children. There were four scales from two instruments that
      resulted in mean scores outside the average range and had statistically
      significant differences. However, the small mean score differences and analyses
      of sensitivity and specificity suggest those scales have limited practical
      usefulness when used by clinicians. 

PMID- 24287881
TI  - Sulforaphane-rich broccoli sprout extract attenuates nasal allergic response to
      diesel exhaust particles.
AB  - The generation of oxidative stress by ambient air pollution particles contributes
      to the development of allergic sensitization and asthma, as demonstrated by
      intranasal challenge with well-characterized diesel exhaust particle (DEP)
      suspensions in humans. This effect is due to the presence of redox active organic
      chemicals in DEP, and can be suppressed by antioxidants and inducers of phase II
      enzymes in animals. In this communication, we determined whether the
      administration of a standardized broccoli sprout extract (BSE), which contains a
      reproducible amount of the sulforaphane (SFN) precursor, glucoraphanin, could be
      used to suppress the nasal inflammatory response in human subjects challenged
      with 300 MUg of an aqueous DEP suspension (equivalent to daily PM exposure levels
      on a Los Angeles freeway). SFN is capable of inducing an antioxidant and phase II
      response via activation of the nuclear transcription factor (erythroid-derived 2)
      like 2 (Nrf2). Previous studies have shown that 70-90% SFN delivered by BSE is
      absorbed, metabolized, and excreted in humans. An initial intranasal challenge
      with DEP in 29 human subjects was used to characterize the magnitude of the
      inflammatory response. Following a 4 week washout, a BSE that delivers a
      reproducible and standardized dose of 100 MUmol SFN in mango juice was
      administered daily for four days. The nasal DEP challenge was repeated and lavage
      fluid collected to perform white blood cell (WBC) counts. The average nasal WBC
      increased by 66% over the initial screening levels and by 85% over the control
      levels 24 hours after DEP exposure. However, total cell counts decreased by 54%
      when DEP challenge was preceded by daily BSE administration for 4 days (p <
      0.001). Since the SFN dose in these studies is equivalent to the consumption of
      100-200 g broccoli, our study demonstrates the potential preventive and
      therapeutic potential of broccoli or broccoli sprouts rich in glucoraphanin for
      reducing the impact of particulate pollution on allergic disease and asthma. 

PMID- 24287880
TI  - Engagement in vocational activities promotes behavioral development for adults
      with autism spectrum disorders.
AB  - This study examined the bidirectional relations over time between behavioral
      functioning (autism symptoms, maladaptive behaviors, activities of daily living)
      and vocational/educational activities of adults with autism spectrum disorders
      (ASD). Participants were 153 adults with ASD (M age = 30.2 years) who were part
      of a larger longitudinal study. Data were collected at two time points separated
      by 5.5 years. Cross-lag models were used, which accounted for stability over time
      while testing both directions of cross-lagged effects. Results suggested that
      greater vocational independence and engagement was related to subsequent
      reductions in autism symptoms and maladaptive behaviors, and improvements in
      activities of daily living. Relations between earlier behavioral variables
      (symptoms, behaviors, and activities of daily living) and later vocational
      independence were not statistically significant. 

PMID- 24287882
TI  - Sleep disturbance in adults with cancer: a systematic review of evidence for best
      practices in assessment and management for clinical practice.
AB  - Sleep disturbance is prevalent in cancer with detrimental effects on health
      outcomes. Sleep problems are seldom identified or addressed in cancer practice.
      The purpose of this review was to identify the evidence base for the assessment
      and management of cancer-related sleep disturbance (insomnia and insomnia
      syndrome) for oncology practice. The search of the health literature included
      grey literature data sources and empirical databases from June 2004 to June 2012.
      The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses,
      psychologists, primary care physicians, oncologists, physicians specialized in
      sleep disturbances, researchers and guideline methodologists to develop clinical
      practice recommendations for pan-Canadian use reported in a separate paper. Three
      clinical practice guidelines and 12 randomized, controlled trials were identified
      as the main source of evidence. Additional guidelines and systematic reviews were
      also reviewed for evidence-based recommendations on the assessment and management
      of insomnia not necessarily in cancer. A need to routinely screen for sleep
      disturbances was identified and the randomized, controlled trial (RCT) evidence
      suggests benefits for cognitive behavioural therapy for improving sleep quality
      in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater
      recognition in clinical practice and in future research.

PMID- 24287884
TI  - Renal transplantation through a modified non-muscle-cutting Pfannenstiel
      incision.
AB  - AIM: To assess the feasibility of performing a renal transplant operation through
      a modified non-muscle-cutting Pfannenstiel incision (MFI). MATERIALS AND METHODS:
      Renal transplantation with MFI was performed in 20 men with a body mass index
      (BMI) of less than 25 and five women with a BMI of less than 27. The parameters
      assessed were incision length, operative time, postoperative pain score by visual
      analogue score, wound complication, graft-related complications, eGFR at 3
      months, and surgical scar satisfaction score. The results were compared with a
      BMI-matched cohort of patients who had a conventional hockey stick incision.
      Statistical analyses were done by Chi-square test and Student's t test. RESULTS:
      There was a significant decrease in mean bed preparation time, mean time for
      closure, and mean incision length in patients with MFI. In MFI group, the mean
      surgical satisfaction score was significantly more. There was no significant
      difference between the groups on all other aspects. CONCLUSION: In the era of
      minimally invasive surgery, MFI technique could challenge the role of
      laparoscopic and robotic surgery in renal transplantation. Our study shows that
      the technique is successful in carefully selected patients with low BMI.

PMID- 24287883
TI  - Keratinocytes produce IL-6 in response to desmoglein 1 cleavage by Staphylococcus
      aureus exfoliative toxin A.
AB  - Many skin infections are caused by Staphylococcus aureus, a bacterial pathogen
      that produces virulence factors associated with these conditions such as
      exfoliative toxins A and B (ETA, ETB) and the leukotoxin Panton-Valentine
      leukocidin (PVL). Herein, we examine the potential of skin-infecting S. aureus to
      produce virulence factors and their impact on the local immune response. Toxin
      gene profiles were generated from 188 S. aureus isolated as single infecting
      organisms from skin lesions and demonstrated a higher potential to express ETA,
      ETB, and PVL than community isolates (p < 0.001). Within the study isolate group,
      the prevalence of genes encoding PVL was higher among methicillin-resistant S.
      aureus (MRSA; n = 49), while genes encoding ETs were more prevalent in
      methicillin-susceptible S. aureus (MSSA; n = 139). When lesion-associated white
      blood cell (WBC) counts were dichotomized into high- or low-WBC-count-associated
      bacteria, the gene for ETA was found to be associated with a low WBC count among
      MSSA (p = 0.001). The ETA-induced mouse model of staphylococcal scalded skin
      syndrome was used to investigate the link between ETA and cytokine production.
      Elevated IL-6 levels in the serum and increased expression of IL-6 mRNA in the
      skin were detected in response to ETA exposure. These findings were recapitulated
      in vitro using primary human keratinocytes. Thus, S. aureus may influence the
      local immune response via ETA cleavage of desmoglein 1 and the induction of
      cutaneous IL-6 expression.

PMID- 24287885
TI  - Protective effect of doxycycline on germinal epithelial loss caused by a high-fat
      diet.
AB  - INTRODUCTION: A high-fat diet and male obesity are aspects associated with
      germinal epithelial alterations and male infertility. Some reports have shown
      that certain tetracyclines can protect the germinal epithelium from toxic drugs.
      The aim of the present study design was to evaluate the possible effect of
      doxycycline on testicular germ cells in individuals fed a Western diet
      (atherogenic), using a murine model. METHODS: Two groups of male mice (BALB/c)
      were fed a high-fat Western diet (HFD). One of these two groups was given
      doxycycline at a dose of 10 mg/kg/day (HFD+Dox). A third group was fed a standard
      rodent diet (SD group). After 6 months, the mice were euthanized and morphologic
      and histopathologic analyses were performed. RESULTS: Germinal epithelial height
      was similar between the SD group (54 MUm) and the HFD+Dox group (53 MUm) (p =
      0.26), and it was significantly reduced in the HFD group (47 MUm) (p = 0.0001).
      The degree of germinal epithelial loss (DGEL) was significantly lower in the SD
      (10) and HFD+Dox (12.5) groups than in the HFD group (30) (p = 0.0001 and =0.007,
      respectively). There were no differences in the DGEL between the SD and HFD+Dox
      groups (p = 0.42). CONCLUSIONS: Doxycycline administration was shown to prevent
      germinal epithelial loss in the testes of mice fed a high-fat diet. Future
      studies are necessary to evaluate the clinical usefulness of doxycycline or its
      analogs in persons with a habitual high-fat diet.

PMID- 24287886
TI  - Comparative genetics of warfarin resistance.
AB  - Warfarin and other 4-hydroxycoumarin-based oral anticoagulants targeting vitamin
      K 2,3-epoxide reductase complex subunit 1 (VKORC1) are administered to humans,
      mice and rats with different purposes in mind - to act as pesticides in high
      dosage baits for killing rodents, but also to save lives when administered in low
      dosages as antithrombotic drugs in humans. However, high-dosage warfarin used to
      control rodent populations has resulted in numerous mutations causing warfarin
      resistance. Currently, six single missense mutations in mice, 12 distinct
      missense mutations in rats, as well as compound heterozygous or homozygous
      mutations with up to six distinct missense mutations per Vkorc1 allele have been
      described. Warfarin resistance missense mutations for human VKORC1 have also been
      found world-wide, but differ characteristically from those in rodents. In humans,
      26 distinct mutations have been characterized, but occur only rarely either in
      heterozygous or, even rarer, in homozygous form. In this review, we summarize the
      known VKORC1 missense mutations causing warfarin and other 4-hydroxycoumarin drug
      resistance, identify genomics databases as new sources of data, explore possible
      underlying genetic mechanisms, and summarize similarities and differences between
      warfarin resistant VKORC1 variants in humans and rodents. 

PMID- 24287887
TI  - In-situ device integration of large-area patterned organic nanowire arrays for
      high-performance optical sensors.
AB  - Single-crystalline organic nanowires (NWs) are important building blocks for
      future low-cost and efficient nano-optoelectronic devices due to their
      extraordinary properties. However, it remains a critical challenge to achieve
      large-scale organic NW array assembly and device integration. Herein, we
      demonstrate a feasible one-step method for large-area patterned growth of cross
      aligned single-crystalline organic NW arrays and their in-situ device integration
      for optical image sensors. The integrated image sensor circuitry contained a 10 *
      10 pixel array in an area of 1.3 * 1.3 mm(2), showing high spatial resolution,
      excellent stability and reproducibility. More importantly, 100% of the pixels
      successfully operated at a high response speed and relatively small pixel-to
      pixel variation. The high yield and high spatial resolution of the operational
      pixels, along with the high integration level of the device, clearly demonstrate
      the great potential of the one-step organic NW array growth and device
      construction approach for large-scale optoelectronic device integration.

PMID- 24287888
TI  - Influence of ionizing dopants on charge transport in organic semiconductors.
AB  - Ionizing chemical dopants are widely used in organic semiconductors to enhance
      the charge transport properties by increasing the number of mobile charge
      carriers. However, together with mobile charges, chemical doping produces anion
      cation pairs in the organic matrix. In this work we use experimental and
      computational analysis to study the influence of these ionic species on the
      charge transport. We show that the anion-cation pairs introduced upon doping have
      a detrimental, doping-level dependent effect on charge mobility. For doping
      levels of 0.02-0.05% molar ratio with respect to the molecular organic
      semiconductor, the increase in conductivity from the extra mobile charges is
      partially cancelled by a reduction in charge mobility from traps introduced by
      the anion-cation pairs. As the doping concentration increases, anion-cation pairs
      start to overlap, resulting in a comparatively smoother potential landscape,
      which increases the charge mobility to values closer to the undoped
      semiconductor. This result has a significant, practical impact, as it shows the
      need to dope at or slightly above a threshold level, which depends on the
      specific host-dopant combination. 

PMID- 24287889
TI  - Causes and timing of delayed bleeding after oral surgery.
AB  - OBJECTIVES: This study examines a cohort of patients who suffered bleeding
      requiring hemostatic intervention after oral surgery. The reasons for bleeding
      and the interval between surgery and onset of bleeding are investigated.
      MATERIALS AND METHODS: Between 1998 and 2009, 1,819 cases were eligible for this
      retrospective study. Factors (independent parameters) influencing the interval
      (dependent variable) were analyzed using negative binomial count regression
      models (NegBin II). The significance of each regressor's effect was tested using
      Wald's test and the total effect using likelihood ratio test. RESULTS: Of the
      patients examined, 1,101 (60.1 %) did not take anticoagulants, 394 (21.5 %) took
      phenprocoumon, 233 (12.7 %) took acetylsalicylic acid, 33 (1.8 %) took
      clopidogrel, 17 (0.9 %) took more than one anticoagulant, and 78 (4.3 %) had a
      congenital blood disorder. After simple tooth extraction, 95.3 % suffered
      bleeding; 69.7 % of extractions were performed in the molar region. Later that
      day of surgery, 66.0 % of all patients showed bleeding. The bleeding interval was
      significantly prolonged by anticoagulant therapy with phenprocoumon, by
      congenital clotting disorders. CONCLUSIONS: Normal tooth extractions are
      underestimated for their risk for postoperative bleeding, especially in the molar
      region. Anticoagulant therapy or congenital blood disorders present oral surgeons
      with a further challenge. CLINICAL RELEVANCE: Performing surgery before midday
      allows surgeons managing postoperative bleeding themselves for a better patient
      satisfaction. Intensified information about correct postoperative behavior is
      crucial. Prolonged blood coagulation should intensify follow-up checks. Patients
      with congenital blood disorders and patients at high risk for bleeding with the
      need for substitution of platelets or clotting factors should receive inpatient
      care. More potent, local applicable coagulant agents are required for these
      patients.

PMID- 24287890
TI  - High-resolution tomography study of the porosity of three restorative resin
      composites.
AB  - OBJECTIVES: The aim of this study was to analyze the porosity of three
      photopolymerizable resin composites: one high-viscous resin composite (FiltekTM
      P60(r), 3 MTM ESPETM), one moderate-viscosity resin composite (Grandio(r),
      VOCOTM), and one low-viscous resin composite (FiltekTM Supreme XTE(r), 3 MTM
      ESPETM). MATERIALS AND METHODS: A total of 36 cylindrical samples with a height
      of 2 mm and a diameter of 2 mm were prepared using PTFE molds. Eighteen cylinders
      were prepared by two incremental applications of 1 mm into the molds, then
      polymerized (group 1). For the other 18 samples (group 2), the first increment
      was polymerized before the second addition was made. The average porosity
      percentage and the average porosity volume were evaluated by high-resolution
      tomography (Nanotom M(r) - Phoenix X-Ray(TM), Wunstorf, Germany). The impact of
      incremental applications in terms of porosity was also evaluated. RESULTS:
      Irrespective of the protocol used, the low viscous material presented an average
      porosity percentage and an average porosity volume significantly greater than
      those of the other materials. Incremental application (group 2 samples) led to an
      increase in the average porosity percentage and volume irrespective of the
      material compared to the group 1 samples. CONCLUSIONS: High-resolution tomography
      appeared to be a particularly suitable tool for studying the porosity of resin
      composites. The viscosity and the handling of these materials seemed to be
      influential factors on their porosity. CLINICAL RELEVANCE: The presence of
      porosities in dental resin composites remains an objective reality, especially
      with low-viscous resin composites. Since the intrinsic porosity of the materials
      can be neither controlled nor modified by the operator, rigorous and iterative
      clinical protocols still remain the best way to limit inclusion of porosities in
      the resin composites.

PMID- 24287891
TI  - In vivo performance of the VistaProof fluorescence-based camera for detection of
      occlusal lesions.
AB  - OBJECTIVES: The aim of this study was to evaluate the in-vivo performance of the
      VistaProof fluorescence-based camera (VP) on occlusal surfaces. METHODS: The
      study was approved by the ethics committee and informed consent was given by the
      participants. The study included 306 unrestored permanent teeth of 26 patients.
      The occlusal surfaces of the teeth were examined visually using International
      Caries Detection and Assessment System (ICDAS) criteria. Then, digital images of
      the surfaces were made using the VP. The actual depth of the lesions was assessed
      using radiographs and/or clinically by opening the lesion when appropriate.
      Correlation between all methods was assessed using Spearman's rank correlation
      coefficient (r s ). Sensitivity (SE) and specificity (SP) were calculated at D1
      (enamel lesions) and D3-(dentine caries) diagnostic threshold and area under the
      ROC curve (AUC) were assessed. RESULTS: Significant positive correlation was
      found between ICDAS, VP measurements and the reference standard (r s 0.46-0.71, p
      < 0.01). SE and SP were at D1-diagnostic threshold level 92.3 and 41.1 %,
      respectively. At D3-diagnostic threshold, SE was 25.9 % and SP 97.9 %. The
      diagnostic performance (AUC) was 0.82 (D1) and 0.85 (D3). Combination of VP
      measurements with ICDAS showed the SE value of 74.1 % at D3-diagnostic threshold.
      CONCLUSION: The VP showed good diagnostic performance. The combination of VP
      measurements with ICDAS improved the SE in detecting dentine lesions.

PMID- 24287892
TI  - Characterization of the Z lineage Major histocompatability complex class I genes
      in zebrafish.
AB  - Zebrafish (Danio rerio) are a valuable model for studying immunity, infection,
      and hematopoietic disease and have recently been employed for transplantation
      assays. However, the lack of syngeneic zebrafish creates challenges with
      identifying immune-matched individuals. The MHC class I genes, which mediate
      allogeneic recognition in mammals, have been grouped into three broad lineages in
      zebrafish: the classical U genes on chromosome 19, the Z genes which have been
      reported to map to chromosome 1, and the L genes that map to multiple loci.
      Transplantations between individual zebrafish that are matched at the U locus
      fail to consistently engraft suggesting that additional loci contribute to
      allogeneic recognition. Although two full-length zebrafish Z transcripts have
      been described, the genomic organization and diversity of these genes have not
      been reported. Herein we define ten Z genes on chromosomes 1 and 3 and on an
      unplaced genomic scaffold. We report that neither of the Z transcripts previously
      described match the current genome assembly and classify these transcripts as
      additional gene loci. We characterize full-length transcripts for 9 of these 12
      genes. We demonstrate a high level of expression variation of the Z genes between
      individual zebrafish suggestive of haplotypic variation. We report low level
      sequence variation for individual Z genes between individual zebrafish reflecting
      a possible nonclassical function, although these molecules may still contribute
      to allogeneic recognition. Finally, we present a gene nomenclature system for the
      Z genes consistent with MHC nomenclature in other species and with the zebrafish
      gene nomenclature guidelines. 

PMID- 24287893
TI  - Microwave absorption properties of core double-shell FeCo/C/BaTiO3
      nanocomposites.
AB  - Microwave absorption properties of core double-shell FeCo/C/(x)BaTiO3
      nanocomposites were investigated in the 1-18 GHz frequency range. High resolution
      transmission electron microscopy studies reveal the core double-shell type
      nanocomposite with FeCo nanoparticles as the center, while carbon and BaTiO3 are
      the inside and the outside shells, respectively. Enhanced relative permittivity
      made the core double-shell FeCo/C/(x)BaTiO3 nanocomposites with better
      electromagnetic impedance matching than that of a FeCo/C and BaTiO3 mixture.
      Reflection loss (RL) values of FeCo/C/(20 wt%)BaTiO3-paraffin composite are
      almost double those of the FeCo/C-paraffin composite at the absorbent thickness
      from 2 to 7.5 mm due to enhanced interfacial effects. The RL value of the
      FeCo/C/(20 wt%)BaTiO3-paraffin composite is -41.7 dB at 11.3 GHz at the absorbent
      thickness of 2 mm and a broad absorption bandwidth of 5.1 GHz (RL values
      exceeding -10 dB) covers the 9.4-14.5 GHz frequency range.

PMID- 24287894
TI  - Environmental and developmental origins of ovarian reserve.
AB  - BACKGROUND Oocyte number is established early in life before a gradual loss of
      this ovarian reserve during reproductive life until oocyte availability becomes
      limiting at the menopause. Although there is a large genetic component to the
      ovarian reserve achieved before birth, other influences including the maternal
      endocrine and nutritional milieu, and environmental factors may represent
      important developmental determinants. Environmental and nutritional factors may
      also modify the downward trajectory of ovarian reserve in adult life. The
      combination of these early and later life influences has the potential to lead to
      diminished ovarian reserve, compromising fertility in later reproductive years
      and altering age at natural menopause. METHODS Literature searches of the ISI Web
      of Knowledge database were carried out using the main terms 'ovarian reserve' and
      'menopause AND age' in conjunction with a range of other terms encompassing a
      variety of factors with potential effects on ovarian reserve. The various
      searches were inspected manually and the relevant papers selected for critical
      analysis and interpretation. RESULTS Evidence was identified supporting the view
      that elevated prenatal androgens have an adverse effect on the early
      establishment of ovarian reserve, although the implications for ovarian reserve
      in the polycystic ovary syndrome (which may also be programmed through prenatal
      androgen exposure) remain uncertain. Recent evidence is cited suggesting that
      effects of maternal nutrient restriction on ovarian reserve may also involve
      changes in prenatal androgen exposure. A general rationale is developed through
      examination of evidence which emphasizes the roles of the aryl hydrocarbon
      receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve
      modulation. Because of their similarity to the natural ligands, many
      environmental compounds have the ability to bind to these receptors (albeit at
      lower affinities) and thereby have the potential to influence either the initial
      setting of ovarian reserve during development or the trajectory of ovarian
      reserve during adult life. For example, exposure to compounds in cigarette smoke
      may accelerate loss of ovarian reserve in smokers leading to diminished ovarian
      reserve, earlier age at last child and earlier menopause. Socioenocomic factors
      are clearly associated with age at natural menopause, with correlations with
      economic status and education level. However, such effects in western societies
      are in general small, and the underlying mechanisms remain unclear. CONCLUSIONS
      Exposure to many environmental compounds, particularly to those that leach from
      plastics and other synthetic materials, is commonplace in modern societies to the
      extent that many are found at measurable concentrations in body fluids within
      most of the population. Relating fluid levels of individual compounds to
      parameters reflecting ovarian reserve in selected populations appears to be an
      effective way forward and, indeed, some early-stage findings do show some cause
      for concern. There is a pressing need for the development of practical advice
      enabling women to minimize their intake of AHR/ER ligands, perhaps through
      dietary/cosmetic choices or improved food packaging. 

PMID- 24287895
TI  - Epigenetic regulation of ASC/TMS1 expression: potential role in apoptosis and
      inflammasome function.
AB  - Cloning studies have revealed that the apoptosis-associated speck-like protein
      possessing a caspase-recruiting domain (ASC) and the target of methylation
      induced silencing-1 (TMS) are identical proteins. ASC/TMS1 is a bipartite adaptor
      protein containing the N-terminal pyrin domain and the C-terminal caspase
      recruitment domain. There is abundant literature on ASC/TMS1, mostly under the
      name TMS1, in the epigenetic regulation of apoptosis and carcinogenesis, whereas
      the abbreviation ASC has been adopted from studies on the assembly of
      inflammasomes and stimulation of inflammation. There is substantial literature
      emphasizing that there are common aspects in the regulation of apoptosis and
      inflammation, which may be related to the function of ASC/TMS1. The region of the
      transcription start site of ASC/TMS1 gene contains a 600-bp-long CpG island that
      is highly methylated and the transcription of ASC/TMS1 is repressed in several
      cancers. However, it is not known whether the ASC/TMS1-dependent epigenetic
      regulation controls the inflammasome functions and moreover whether this
      regulation has any role in the inflammation-mediated carcinogenesis or in the
      pathogenesis of age-related degenerative diseases. We will examine the mechanisms
      involved in the epigenetic regulation of ASC/TMS1 as well as their significance
      in the coordination of apoptosis and inflammasome functions. We will also review
      the role of aberrant methylation of ASC/TMS1 promoter in the function of
      inflammasomes, a major host defense system, in cellular housekeeping and
      carcinogenesis. 

PMID- 24287897
TI  - Re: Adherence to NICE guidelines for new glaucoma referrals.

PMID- 24287898
TI  - Inaccuracy of ROP screening data in National Neonatal Audit Programme report.

PMID- 24287896
TI  - Signaling pathways and the cerebral cavernous malformations proteins: lessons
      from structural biology.
AB  - Cerebral cavernous malformations (CCM) are neurovascular dysplasias that result
      in mulberry-shaped lesions predominantly located in brain and spinal tissues.
      Mutations in three genes are associated with CCM. These genes encode for the
      proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations
      1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3
      (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell
      death 10 (CCM3/PDCD10). There have been many significant recent advances in our
      understanding of the structure and function of these proteins, as well as in
      their roles in cellular signaling. Here, we provide an update on the current
      knowledge of the structure of the CCM proteins and their functions within
      cellular signaling, particularly in cellular adhesion complexes and signaling
      cascades. We go on to discuss subcellular localization of the CCM proteins, the
      formation and regulation of the CCM complex signaling platform, and current
      progress towards targeted therapy for CCM disease. Recent structural studies have
      begun to shed new light on CCM protein function, and we focus here on how these
      studies have helped inform the current understanding of these roles and how they
      may aid future studies into both CCM-related biology and disease mechanisms. 

PMID- 24287899
TI  - IgE reactivity to Acarus siro extract in Korean dust mite allergic patients.
AB  - Although specific IgE to the storage mite Acarus siro is often detected, there
      are no detailed studies on IgE reactivity to A. siro in Korea. This study was
      undertaken to investigate the cross-reactivity to the mite species
      Dermatophagoides pteronyssinus, Dermatophagoides farinae, Tyrophagus
      putrescentiae, and A. siro in Korean mite allergic patients. Specific IgE values
      were determined for the four mite species and a competitive inhibition test was
      performed for mite extracts using the ImmunoCAP system. The IgE value to D.
      farinae was the highest among the four mite species tested. There was a strong
      correlation in the IgE value between house dust mites (D. pteronyssinus and D.
      farinae) and between storage mites (A. siro and T. putrescentiae). IgE reactivity
      to A. siro was inhibited by D. farinae and T. putrescentiae extract.
      Dermatophagoides farinae extract was the strongest inhibitor of IgE binding to A.
      siro extract, indicating that IgE reactivity to A. siro extract is a cross
      reaction caused by sensitization to D. farinae. Strong IgE reactive components
      were observed in D. farinae and T. putrescentiae extract by SDS-PAGE and IgE
      immunoblotting. However, no strong IgE-binding component was observed for A.
      siro. Dermatophagoides farinae is the main source of mite allergens that cause
      sensitization in Korea. Serum IgE from some of the house dust mite-sensitized
      patients showed positive responses to storage mite allergens by cross-reaction.
      Therefore, it is necessary to pay special attention to the diagnosis of mite
      allergies.

PMID- 24287900
TI  - Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma
      cells.
AB  - Autophagy, a self-defense mechanism, has been found to be associated with drug
      resistance in hepatocellular carcinoma (HCC). Our study was designed to
      investigate the role and related mechanisms of autophagy in matrine-induced
      apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by
      flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity
      and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming
      assay were used to assess the effect of matrine on growth and proliferation of
      HCC cells. Autophagic flux in HCC cells was analyzed using the expression of
      LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron
      microscopy. Moreover, regarding to the associated mechanisms, the effects of
      matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were
      studied. Our results showed that: (1) both autophagy and apoptosis could be
      induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine
      and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be
      enhanced in a caspase-dependent manner; and (3) autophagy was induced via
      inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion,
      inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma
      cells. 

PMID- 24287901
TI  - The homeobox only protein homeobox (HOPX) and colorectal cancer.
AB  - The HOP (homeobox only protein) homeobox (HOPX) is most closely related to the
      homeobox protein that contains a homeobox-like domain but lacks certain conserved
      residues required for DNA binding. Here, we review the current understanding of
      HOPX in the progression of colorectal cancer (CRC). HOPX was initially reported
      as a differentiation marker and is expressed in various normal tissues. In the
      colon, HOPX is expressed uniquely in the quiescent stem cell, +4, and in
      differentiated mucosal cells of the colon. HOPX expression is markedly suppressed
      in a subset of cancers, mainly in an epigenetic manner. CRC may include separate
      entities which are differentially characterized by HOPX expression from a
      prognostic point of view. HOPX itself can regulate epigenetics, and defective
      expression of HOPX can result in loss of tumor suppressive function and
      differentiation phenotype. These findings indicate that HOPX may be both a
      central regulator of epigenetic dynamics and a critical determinant for
      differentiation in human cells. HOPX downstream targets were identified in CRC
      cell lines and hold promise as candidates for therapeutic targets of CRC, such as
      EphA2 or AP-1. Further analysis will elucidate and confirm the precise role of
      such proteins in CRC progression. 

PMID- 24287902
TI  - Screening of peptide ligands for pyrroloquinoline quinone glucose dehydrogenase
      using antagonistic template-based biopanning.
AB  - We have developed a novel method, antagonistic template-based biopanning, for
      screening peptide ligands specifically recognizing local tertiary protein
      structures. We chose water-soluble pyrroloquinoline quinone (PQQ) glucose
      dehydrogenase (GDH-B) as a model enzyme for this screening. Two GDH-B mutants
      were constructed as antagonistic templates; these have some point mutations to
      induce disruption of local tertiary structures within the loop regions that are
      located at near glucose-binding pocket. Using phage display, we selected 12-mer
      peptides that specifically bound to wild-type GDH-B but not to the antagonistic
      templates. Consequently, a peptide ligand showing inhibitory activity against GDH
      B was obtained. These results demonstrate that the antagonistic template-based
      biopanning is useful for screening peptide ligands recognizing the specific local
      tertiary structure of proteins. 

PMID- 24287903
TI  - Synthesis of 1,4-bis(phenylethynyl)benzenes and their application as blue phase
      liquid crystal composition.
AB  - A number of 1,4-bis(phenylethynyl)benzene derivatives (BPEBs) and their analogues
      with different numbers of side-substitute fluorine atoms on benzene rings, and
      alkyl chains, ethoxyl groups, fluorine atoms and trifluoromethyl groups as the
      end groups have been synthesized. The effects of the different substituents on
      their properties such as thermal behavior of melting point and clearing point,
      the temperature of nematic phase, optical anisotropy and dielectric anisotropy
      have been well investigated, and it has been found that some BPEBs have a wide
      range of the nematic phase temperature with high optical anisotropy (Deltan) and
      acceptable dielectric anisotropy (Deltaepsilon), which have been applied as the
      crucial compositions to constitute a liquid crystal mixture having the properties
      of Deltaepsilon=29.0 and Deltan=0.283 at 25  degrees C. With the addition of the
      chiral dopant to the obtained liquid crystal mixture, blue phase liquid crystal
      with a blue phase temperature range of 8  degrees C has been achieved.

PMID- 24287905
TI  - An exploratory evaluation of tyrosine hydroxylase inhibition in planaria as a
      model for parkinsonism.
AB  - Planaria are the simplest organisms with bilateral symmetry and a central nervous
      system (CNS) with cephalization; therefore, they could be useful as model
      organisms to investigate mechanistic aspects of parkinsonism and to screen
      potential therapeutic agents. Taking advantage of the organism's anti-tropism
      towards light, we measured a significantly reduced locomotor velocity in planaria
      after exposure to 3-iodo-L-tyrosine, an inhibitor of tyrosine hydroxylase that is
      an enzyme catalyzing the first and rate-limiting step in the biosynthesis of
      catecholamines. A simple semi-automatic assay using videotaped experiments and
      subsequent evaluation by tracking software was also implemented to increase
      throughput. The dopaminergic regulation of locomotor velocity was confirmed by
      bromocriptine, a drug whose mechanisms of action to treat Parkinson's disease is
      believed to be through the stimulation of nerves that control movement. 

PMID- 24287904
TI  - Mevalonate kinase deficiency and neuroinflammation: balance between apoptosis and
      pyroptosis.
AB  - Mevalonic aciduria, a rare autosomal recessive disease, represents the most
      severe form of the periodic fever, known as Mevalonate Kinase Deficiency. This
      disease is caused by the mutation of the MVK gene, which codes for the enzyme
      mevalonate kinase, along the cholesterol pathway. Mevalonic aciduria patients
      show recurrent fever episodes with associated inflammatory symptoms, severe
      neurologic impairments, or death, in early childhood. The typical
      neurodegeneration occurring in mevalonic aciduria is linked both to the intrinsic
      apoptosis pathway (caspase-3 and -9), which is triggered by mitochondrial damage,
      and to pyroptosis (caspase-1). These cell death mechanisms seem to be also
      related to the assembly of the inflammasome, which may, in turn, activate pro
      inflammatory cytokines and chemokines. Thus, this particular molecular platform
      may play a crucial role in neuroinflammation mechanisms. Nowadays, a specific
      therapy is still lacking and the pathogenic mechanisms involving
      neuroinflammation and neuronal dysfunction have not yet been completely
      understood, making mevalonic aciduria an orphan drug disease. This review aims to
      analyze the relationship among neuroinflammation, mitochondrial damage,
      programmed cell death, and neurodegeneration. Targeting inflammation and
      degeneration in the central nervous system might help identify promising
      treatment approaches for mevalonic aciduria or other diseases in which these
      mechanisms are involved. 

PMID- 24287906
TI  - The EPS matrix as an adaptive bastion for biofilms: introduction to special
      issue.

PMID- 24287907
TI  - The effect of carbon monoxide Co-adsorption on Ni-catalysed water dissociation.
AB  - The effect of carbon monoxide (CO) co-adsorption on the dissociation of water on
      the Ni(111) surface has been studied using density functional theory. The
      structures of the adsorbed water molecule and of the transition state are changed
      by the presence of the CO molecule. The water O-H bond that is closest to the CO
      is lengthened compared to the structure in the absence of the CO, and the
      breaking O-H bond in the transition state structure has a larger imaginary
      frequency in the presence of CO. In addition, the distances between the Ni
      surface and H2O reactant and OH and H products decrease in the presence of the
      CO. The changes in structures and vibrational frequencies lead to a reaction
      energy that is 0.17 eV less exothermic in the presence of the CO, and an
      activation barrier that is 0.12 eV larger in the presence of the CO. At 463 K the
      water dissociation rate constant is an order of magnitude smaller in the presence
      of the CO. This reveals that far fewer water molecules will dissociate in the
      presence of CO under reaction conditions that are typical for the water-gas-shift
      reaction. 

PMID- 24287908
TI  - Self/co-assembling peptide, EAR8-II, as a potential carrier for a hydrophobic
      anticancer drug pirarubicin (THP)--characterization and in-vitro delivery.
AB  - A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the
      hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit
      advantages from two previously introduced peptides, AAP8 and EAK16-II, in their
      self/co-assembly. This peptide is short, simple, and inexpensive to synthesize,
      while possessing a low critical assembly concentration (CAC). The choice of
      alanine (A) residues in the peptide sequence provides moderate hydrophobic
      interactions, causing a minimal degree of aggregation, compared with other more
      hydrophobic residues. EAR8-II is an ionic-complementary peptide, similar to EAK16
      II, can self/co-assemble with hydrophobic compounds such as THP, and forms a
      stable fibular nanostructure in aqueous solution. Physiochemical properties and
      cellular activities of the EAR8-II and THP complexes were evaluated and show
      dependency on the peptide-to-drug ratio. The complex at the peptide-to-drug mass
      ratio of 5:1 provides a stable solution, uniform nanostructure, and highly
      effective anticancer activity against various cancer cell lines. This work forms
      the basis for detailed studies on EAR8-II and THP formulations in vitro and in
      vivo, for future development of peptide-based delivery systems for hydrophobic
      anticancer drugs. 

PMID- 24287909
TI  - Biological significance of calbindin-D9k within duodenal epithelium.
AB  - Calbindin-D9k (CaBP-9k) binds calcium with high affinity and regulates the
      distribution of free calcium in the cytoplasm. The expression of CaBP-9k is
      detected primarily in intestine that is vitamin D target tissue, and accumulates
      in the enterocytes of the duodenal villi. These enterocytes are the clearest
      example of vitamin D responsive cells, and the presence of CaBP-9k within them
      accentuates calcium absorption mediated by active transcellular calcium
      transport. It has been well established that the expression of CaBP-9k is
      mediated with vitamin D response element on its promoter and it regulates the
      amount of intracellular calcium in order to prevent cell death from reaching the
      toxicity of free calcium. There is now little doubt that glucocorticoid also
      decreases CaBP-9k expression in duodenal epithelial cells. In addition, it was
      reported that the level of CaBP-9k gene in enterocytes is increased in pregnancy
      when the plasma estradiol concentration is generally associated with a
      concomitant increase. Although calcium homeostasis was not disturbed in mice
      lacking the CaBP-9k gene, we found that CaBP-9k has a buffering role of free
      calcium in the cytosolic environment beyond that of calcium transfer. To expand
      our knowledge of the biological functions of CaBP-9k, our research has focused on
      defining the biological significance of intracellular CaBP-9k. Our findings
      suggest that the CaBP-9k gene is involved in compensatory induction of other
      calcium transporter genes in duodenal epithelial cells. This article summarizes
      the findings from recent studies on the expression and the functions of CaBP-9k
      in the small intestine. 

PMID- 24287910
TI  - Does the neuroprotective role of anandamide display diurnal variations?
AB  - The endocannabinoid system is a component of the neuroprotective mechanisms that
      an organism displays after traumatic brain injury (TBI). A diurnal variation in
      several components of this system has been reported. This variation may influence
      the recovery and survival rate after TBI. We have previously reported that the
      recovery and survival rate of rats is higher if TBI occurs at 1:00 than at 13:00.
      This could be explained by a diurnal variation of the endocannabinoid system.
      Here, we describe the effects of anandamide administration in rats prior to the
      induction of TBI at two different times of the day: 1:00 and 13:00. We found that
      anandamide reduced the neurological damage at both times. Nevertheless, its
      effects on bleeding, survival, food intake, and body weight were dependent on the
      time of TBI. In addition, we analyzed the diurnal variation of the expression of
      the cannabinoid receptors CB1R and CB2R in the cerebral cortex of both control
      rats and rats subjected to TBI. We found that CB1R protein was expressed more
      during the day, whereas its mRNA level was higher during the night. We did not
      find a diurnal variation for the CB2R. In addition, we also found that TBI
      increased CB1R and CB2R in the contralateral hemisphere and disrupted the CB1R
      diurnal cycle. 

PMID- 24287911
TI  - Modification of pectin and hemicellulose polysaccharides in relation to aril
      breakdown of harvested longan fruit.
AB  - To investigate the modification of cell wall polysaccharides in relation to aril
      breakdown in harvested longan fruit, three pectin fractions (WSP, water soluble
      pectin; CSP, CDTA-soluble pectin; ASP, alkali soluble pectin) and one
      hemicellulose fraction (4 M KOH-SHC, 4 M KOH-soluble hemicellulose) were
      extracted, and their contents, monosaccharide compositions and molecular weights
      were evaluated. As aril breakdown intensified, CSP content increased while ASP
      and 4 M KOH-SHC contents decreased, suggesting the solubilization and conversion
      of cell wall components. Furthermore, the molar percentage of arabinose (Ara), as
      the main component of the side-chains, decreased largely in CSP and ASP while
      that of rhamnose (Rha), as branch point for the attachment of neutral sugar side
      chains, increased during aril breakdown. Analysis of (Ara+Gal)/Rha ratio showed
      that the depolymerization of CSP and ASP happened predominantly in side-chains
      formed of Ara residues. For 4 M KOH-SHC, more backbones were depolymerized during
      aril breakdown. Moreover, it was found that the molecular weights of CSP, ASP and
      4 M KOH-SHC polysaccharides tended to decrease as aril breakdown intensified.
      These results suggest that both enhanced depolymerization and structural
      modifications of polysaccharides in the CSP, ASP and 4 M KOH-SHC fractions might
      be responsible for aril breakdown of harvested longan fruit.

PMID- 24287912
TI  - Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues.
AB  - Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range
      of pharmacological properties. Resveratrol is also known as a good
      chemopreventive agent for inhibiting carcinogenesis processes that target
      kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total
      of 19 analogues with an amide moiety were synthesized and the cytotoxic effects
      of the analogues on a series of human cancer cell lines are reported. Three
      compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145
      (IC50=16.68 uM), colon cancer HT-29 (IC50=7.51 uM) and breast cancer MCF-7
      (IC50=21.24 uM), respectively, which are comparable with vinblastine. The
      resveratrol analogues were synthesized using the Heck method.

PMID- 24287913
TI  - Regenerative medicine for epilepsy: from basic research to clinical application.
AB  - Epilepsy is a chronic neurological disorder, which presents with various forms of
      seizures. Traditional treatments, including medication using antiepileptic drugs,
      remain the treatment of choice for epilepsy. Recent development in surgical
      techniques and approaches has improved treatment outcomes. However, several
      epileptic patients still suffer from intractable seizures despite the advent of
      the multimodality of therapies. In this article, we initially provide an overview
      of clinical presentation of epilepsy then describe clinically relevant animal
      models of epilepsy. Subsequently, we discuss the concepts of regenerative
      medicine including cell therapy, neuroprotective agents, and electrical
      stimulation, which are reviewed within the context of our data. 

PMID- 24287915
TI  - Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced
      melanogenesis.
AB  - Melanin is responsible for skin color and plays a major role in defending against
      harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is
      responsible for the critical steps of melanogenesis, including the rate-limiting
      step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting
      agents are thought to be based on the ability of a given agent to inhibit the
      activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and
      its glycoside, salidroside, are active components of Rhodiola rosea, and in our
      preliminary study we found that Rhodiola rosea extract inhibited melanogenesis.
      In this study, we examined the effects of tyrosol and its analogues on melanin
      synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4
      hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2
      hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in
      melanin content and inhibition of tyrosinase activity as well as its expression.
      Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7)
      suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3
      hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited alpha
      MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did
      not affect MITF and TRP-2 expression. Furthermore, we found that the cell
      viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic
      acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and
      salidroside (11) at concentrations below 0.5 mM were higher than 90%. The
      compounds exhibited metal-coordinating interactions with copper ion in molecular
      docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic
      acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are
      potential hypopigmenting agents. 

PMID- 24287914
TI  - Role of Sam68 in post-transcriptional gene regulation.
AB  - The STAR family of proteins links signaling pathways to various aspects of post
      transcriptional regulation and processing of RNAs. Sam68 belongs to this class of
      heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain
      containing family of RNA-binding proteins that also contains some domains
      predicted to bind critical components in signal transduction pathways. In
      response to phosphorylation and other post-transcriptional modifications, Sam68
      has been shown to have the ability to link signal transduction pathways to
      downstream effects regulating RNA metabolism, including transcription,
      alternative splicing or RNA transport. In addition to its function as a docking
      protein in some signaling pathways, this prototypic STAR protein has been
      identified to have a nuclear localization and to take part in the formation of
      both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies
      and stress granules. Coupling with other proteins and RNA targets, Sam68 may play
      a role in the regulation of differential expression and mRNA processing and
      translation according to internal and external signals, thus mediating important
      physiological functions, such as cell death, proliferation or cell
      differentiation. 

PMID- 24287916
TI  - Bone morphogenetic protein-7 ameliorates cerebral ischemia and reperfusion injury
      via inhibiting oxidative stress and neuronal apoptosis.
AB  - Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) is
      neuroprotective against cerebral ischemia/reperfusion (IR) injury. The present
      study was undertaken to determine the molecular mechanisms involved in this
      effect. Adult male Wistar rats were subjected to 2 h of transient middle cerebral
      artery occlusion (MCAO), followed by 24 h of reperfusion. BMP-7 (10-4 g/kg) or
      vehicle was infused into rats at the onset of reperfusion via the tail vein.
      Neurological deficits, infarct volume, histopathological changes, oxidative
      stress-related biochemical parameters, neuronal apoptosis, and apoptosis-related
      proteins were assessed. BMP-7 significantly improved neurological and
      histological deficits, reduced the infarct volume, and decreased apoptotic cells
      after cerebral ischemia. BMP-7 also markedly enhanced the activities of
      antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH
      PX), and reduced the level of malondialdehyde (MDA) in IR rats. In addition,
      Western blot analysis indicated that BMP-7 prevented cytochrome c release,
      inhibited activation of caspase-3, caspase-9 and caspase-8. Our data suggested
      that BMP-7 has protective effects against cerebral IR injury in rats, and the
      neuroprotective effects may be attributed to attenuating oxidative stress and
      inhibiting neuronal apoptosis. 

PMID- 24287917
TI  - Genetic diversity and conservation of the Prespa trout in the Balkans.
AB  - The Balkans are known to have a high level of biodiversity and endemism. No less
      than 15 taxa have been recorded in salmonids of the Salmo genus. Among them, the
      Prespa trout is found in only four river systems flowing into Lake Macro Prespa,
      three in the Former Yugoslav Republic of Macedonia and one in Greece. This is the
      first comprehensive survey of all streams located within the Macro Prespa Basin,
      encompassing the whole taxon range. A large genetic sample of 536 Prespa trout
      was collected mainly between 2005 and 2007. The sampling included 59 individuals
      from the Golema river system, 93 from the Kranska, 260 from the Brajcinska, 119
      from the Agios Germanos, and five individuals from the lake itself. These
      specimens were analyzed with six microsatellite markers and by sequencing the
      mitochondrial control region. Nuclear data were examined through multidimensional
      analysis and assignment tests. Five clusters were detected by assignment: Golema,
      Kranska, Brajcinska upstream, Rzanska Brajcinska tributary and Brajcinska
      downstream. Most of these river systems thus hosted differentiated Prespa trout
      populations (with past gene flows likely dating before the construction of dams),
      except Agios Germanos, which was found to be composed of 5% to 32% of each
      cluster. Among the five trout individuals from the lake, four originated from
      Kranska River and one was admixed. Supported parsimonious hypotheses are proposed
      to explain these specificities. Conservation of this endemic taxon should take
      these results into account. No translocation should be performed between
      different tributaries of the lake and preservation of the Brajcinska populations
      should address the upstream-downstream differentiation described. 

PMID- 24287919
TI  - Application of DNA machine in amplified DNA detection.
AB  - A DNA machine finds its application to construct an enzyme-free, label-free, cost
      effective and novel approach for amplified DNA detection. The present approach is
      endowed with high sensitivity and selectivity. A detection limit as low as 0.2 nM
      was obtained by practical measurement. 

PMID- 24287918
TI  - Up-regulation of mRNA ventricular PRNP prion protein gene expression in air
      pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose
      regulated protein 78, and nanosized particles.
AB  - Mexico City Metropolitan Area children and young adults exposed to high
      concentrations of air pollutants including fine and ultrafine particulate matter
      (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome
      activation with a differential right and left ventricular expression of key
      inflammatory genes and inflammasomes. We investigated the mRNA expression levels
      of the prion protein gene PRNP, which plays an important role in the protection
      against oxidative stress and metal toxicity, and the glucose regulated protein
      78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular
      autopsy samples from 30 children and young adults age 19.97 +/- 6.8 years with a
      lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy
      and transmission electron microscopy studies were carried out in human
      ventricles, and electron microscopy studies were also done in 5 young, highly
      exposed Mexico City dogs. There was significant left ventricular PRNP and bi
      ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls.
      PRNP up-regulation in the left ventricle was significantly different from the
      right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78
      correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells,
      numerous nanosized particles in myocardial ER and in abnormal mitochondria
      characterized the highly exposed ventricles. Early and sustained cardiac ER
      stress could result in detrimental irreversible consequences in urban children,
      and while highly complex systems maintain myocardial homeostasis, failure to
      compensate for chronic myocardial inflammation, oxidative and ER stress, and
      particles damaging myocardial organelles may prime the development of
      pathophysiological cardiovascular states in young urbanites. Nanosized PM could
      play a key cardiac myocyte toxicity role. 

PMID- 24287920
TI  - Enhanced luminescence of CaMoO4:Eu by core@shell formation and its hyperthermia
      study after hybrid formation with Fe3O4: cytotoxicity assessment on human liver
      cancer cells and mesenchymal stem cells.
AB  - Highly water dispersible Eu3+ doped CaMoO4 nanoparticles (core) covered by CaMoO4
      (shell) have been prepared using the polyol method. Significant enhancement in
      luminescence intensity by core@shell formation is observed due to the decrease of
      non-radiative rate arising from surface/defect of particles. Effect of 266 nm
      laser excitation (Mo-O charge transfer band) on the asymmetric ratio (A21 =
      intensity ratio of electric to magnetic dipole transitions) has been studied and
      compared with a xenon lamp source. Luminescence intensity increases with the
      increase of power at 532 nm laser excitation. In order to explore materials,
      which can show dual functionalities such as luminescence as well as magnetic
      properties (magnetization of ~14.2 emu g-1), water dispersible Fe3O4-CaMoO4:Eu
      hybrid magnetic nanoparticles (MN) have been prepared. This shows good heating
      ability up to ~42  degrees C (hyperthermia) and luminescence in the red region
      (~612 nm), which is in a biological window (optical imaging). Biocompatibility of
      the synthesized Fe3O4-CaMoO4:Eu hybrid magnetic nanoparticles has been evaluated
      in vitro by assessing their cytotoxicity on human liver cancer cells (HepG2
      cells) and hTERT cells using the MTT assay and fluorescent microscopy studies.

PMID- 24287921
TI  - A non-mosaic isodicentric Y chromosome resulting from breakage and fusion at the
      Yq pseudo-autosomal region in a fetus.
AB  - The dicentric Y chromosomes are the most commonly found in the structural
      aberration of Y chromosome. If the dicentric chromosome has completely symmetric
      arms, it is considered an isodicentric chromosome. The sites of breakage and
      fusion at Yp and Yq are variable, but breakage and fusion at the pseudo-autosomal
      region has never been reported. Herein we reported identification de novo
      isodicentric (Yq12) in a fetus. The fusion occurred at Yq pseudo-autosomal region
      very close the telomere and resulted in duplication of Y chromosome. The baby was
      grossly normal at birth. In conclusion, isodicentric Y chromosome could result
      from breakage and fusion at the Yq pseudo-autosomal region. 

PMID- 24287922
TI  - Ginsenoside Rg1 decreases neurofibrillary tangles accumulation in retina by
      regulating activities of neprilysin and PKA in retinal cells of AD mice model.
AB  - Neurofibrillary tangles (NFTs) are the major component of senile plaques in the
      brains of patients with Alzheimer's disease (AD). However, the mechanism causing
      NFTs accumulation in AD patients' retina is also elusive. Thus, we investigated
      the effects of ginsenoside Rg1 on NFTs accumulation in retinal pigment epithelial
      (RPE) cells isolated form double transgenic APP/PS1 mice model. NFTs amounts in
      culture supernatants were examined by enzyme-linked immunosorbent assay. Activity
      and mRNA transcription of enzymes and proteins that regulate NFTs accumulation
      were examined by activity assay and reverse transcription PCR. The expression of
      neprilysin (NEP) and neutral endopeptidase (PKA) were detected by western blot
      assay. Rg1 significantly decreased NFTs accumulation in isolated RPE cells.
      Activity of NEP was significantly increased, and activity of PKA was
      significantly decreased in cell lysates of Rg1-feeding APP/PS1 mice compared with
      non-Rg1-feeding mice. mRNA level of NEP was significantly higher and mRNA level
      of PKA was significantly lower in cells of Rg1-feeding mice than nonfeeding mice.
      The phosphorylation of tau at Thr231, Thr205, and Ser396 were significantly
      decreased in RPE of Rg1-feeding APP/PS1 mice compared with the non-Rg1-feeding
      mice. Rg1 decreased the NFTs production in RPE cell of APP/PS1 mice by modulating
      the expression and activity of NEP and PKA, which perform the function through
      downregulating the phosphorylation of tau protein. 

PMID- 24287923
TI  - Comparative genomic sequence analysis between a standard challenge strain and a
      vaccine strain of duck enteritis virus in China.
AB  - Here, we present the complete genomic sequence of the Chinese standard challenge
      strain (CSC) of duck enteritis virus (DEV), which was isolated in China in 1962.
      The DEV CSC genome is 162,131 bp long and contains 78 predicted open reading
      frames (ORFs). Comparison of the genomic sequences of DEV CSC and DEV live
      vaccine strain K at passage 63 (DEV K p63) revealed that the DEV CSC genome is
      4,040 bp longer than the DEV K p63 genome, mainly because of 3,513-bp and 528-bp
      insertions at the 5' and 3' ends of the unique long segment, respectively. At the
      nucleotide level, 63 of the 76 ORFs in the DEV CSC genome were 100 % identical to
      the ORFs in the DEV K p63 genome. Two ORFs (UL56 and US10) had frameshift
      mutations in the C-terminal regions, while LORF5 was unique to the DEV K p63
      genome. It is difficult to assign attenuated virulence to changes in specific
      genes. However, the complete DEV CSC genome will further advance our
      understanding of the genes involved in virulence and evolution. The DEV CSC
      genome sequence has been deposited in GenBank under accession number JQ673560.

PMID- 24287924
TI  - Molecular characterization and phylogenetic study of velogenic Newcastle disease
      virus isolates in Iran.
AB  - The pathogenicity and genetic characterizations of six Newcastle disease virus
      (NDV) isolates obtained from chicken farms in six different regions in Iran were
      carried out using conventional and molecular techniques. Based on the
      pathogenicity indices (MDT, ICPI, and IVPI), all of these isolates were found to
      be velogenic (highly virulent) strains. A sequence analysis of the full-length
      mRNA encoding the fusion glycoprotein precursor (F0) of the NDV's fusion proteins
      F1 and F2 in these six isolates showed the presence of point mutations in form of
      nucleic acid substitutions at positions 82((C->T)), 83((T->C)), 736((A->G)), and
      1,633((G->A)). However, the nucleic acid residues at positions 330-347 of the
      precursor F0 gene, corresponding to the cleavage site of the F0 protein, were
      found to have remained conserved among the six NDV isolates. A phylogenetic
      comparison between the six Iranian isolates and the NDVs whose F0 gene sequences
      were previously deposited in GenBank Database showed that all of the newly
      characterized Iranian NDV isolates belonged to genotype VII.

PMID- 24287925
TI  - Characteristics of rib cartilage calcification in Asian patients.
AB  - IMPORTANCE Rib cartilage from the sixth, seventh, and eighth ribs offers a long
      cartilaginous curvature, making the material reliable for grafting. Calcification
      of cartilage causes unexpected absorption, difficult manipulation, and donor site
      morbidity. Most studies of calcification were performed in Western countries.
      OBJECTIVE To investigate the incidence, degree, and pattern of rib cartilage
      calcification in Asian patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective
      study of computed tomographic scans of the chest in 120 patients (60 male and 60
      female). The incidence, degree, and pattern of cartilage calcification of the
      sixth through eighth ribs were noted. The patients were stratified into 6 age
      groups, and 20 patients (10 male and 10 female) were selected for each group. The
      degree of calcification was assessed as 0%, 1% to 25%, 26% to 50%, 51% to 75%,
      and 76% to 100%. Meaningful calcification was defined as 26% or greater. The
      pattern of calcification was classified as marginal, granular, and central.
      EXPOSURE Computed tomographic scans of the chest. MAIN OUTCOMES AND MEASURES
      Degree of calcification, presence of meaningful calcification, and calcification
      pattern. RESULTS Overall, 50.8% of cartilage was calcified, and female patients
      showed more frequent calcification than male patients (59.4% vs 42.2% [P <
      .001]). Calcification rates of the sixth and seventh rib cartilage were higher
      than those of the eighth rib cartilage in all age groups except teenagers, who
      had a similar rate for all 3 ribs. Calcification of the sixth and seventh rib
      cartilage significantly increased with age. A meaningful calcification rate was
      very low in males younger than 60 years, whereas the rate was relatively higher
      in females than males for all age groups. Males predominantly had the marginal
      type of calcification, whereas females predominantly had a granular type. The
      rate and pattern of calcification had no relationship to age. CONCLUSIONS AND
      RELEVANCE In Asian patients, males younger than 60 years show a very low
      incidence of calcification, whereas females 30 years or older show a relatively
      high incidence of meaningful calcification. Asian females also show a
      predominantly granular or central pattern of calcification that may hinder proper
      harvest and incision of the rib cartilage. These differences in the incidence and
      pattern of rib cartilage calcification need appropriate preoperative attention.

PMID- 24287926
TI  - The DNA-forming properties of 6-selenoguanine.
AB  - We present here an exhaustive characterization of the structure and properties of
      6-selenoguanine, an isoster of guanine, and the impact of its introduction in
      DNA. This study reports the results of state-of-the-art quantum mechanical
      calculations and atomistic molecular dynamics simulations carried out to shed
      light on the impact of the replacement of guanine (G) by 6-selenoguanine (SeG) in
      different forms of DNA. The results point out that the G -> SeG substitution
      leads to stable DNA duplex, antiparallel triplex and G-quadruplex structures,
      though local distortions are also found. These structural changes affect the
      thermodynamic stability of the mutation leading to a clear destabilization for
      all studied systems. Interestingly, the lowest effect has been found when the
      mutation was placed in the triplex-forming oligonucleotide strand in a reverse
      Hoogsteen orientation, which favours the antiparallel triplex formation regarding
      the G-tetraplex formation. Detailed QM studies strongly suggest that SeG impacts
      the HOMO-LUMO gap and accordingly the transfer properties of DNA, opening the way
      to modulate the conductivity properties of non-natural DNAs. 

PMID- 24287927
TI  - Influence of N- and/or C-terminal regions on activity, expression,
      characteristics and structure of lipase from Geobacillus sp. 95.
AB  - GD-95 lipase from Geobacillus sp. strain 95 and its modified variants lacking N
      terminal signal peptide and/or 10 or 20 C-terminal amino acids were successfully
      cloned, expressed and purified. To our knowledge, GD-95 lipase precursor (Pre-GD
      95) is the first Geobacillus lipase possessing more than 80% lipolytic activity
      at 5  degrees C. It has maximum activity at 55  degrees C and displays a broad pH
      activity range. GD-95 lipase was shown to hydrolyze p-NP dodecanoate, tricaprylin
      and canola oil better than other analyzed substrates. Structural and sequence
      alignments of bacterial lipases and GD-95 lipase revealed that the C-terminus
      forms an alpha helix, which is a conserved structure in lipases from Pseudomonas,
      Clostridium or Staphylococcus bacteria. This work demonstrates that 10 and 20 C
      terminal amino acids of GD-95 lipase significantly affect stability and other
      physicochemical properties of this enzyme, which has never been reported before
      and can help create lipases with more specific properties for industrial
      application. GD-95 lipase and its modified variants GD-95-10 can be successfully
      applied to biofuel production, in leather and pulp industries, for the production
      of cosmetics or perfumes. These lipases are potential biocatalysts in processes,
      which require extreme conditions: low or high temperature, strongly acidic or
      alkaline environment and various organic solvents.

PMID- 24287929
TI  - Correlation between plasma miR-122 expression and liver injury induced by
      hepatectomy.
AB  - OBJECTIVE: This study aimed to define the correlation between microRNA-122 (miR
      122) expression and hepatectomy-induced liver injury in patients with
      hepatocellular carcinoma (HCC). METHODS: Plasma miR-122 expression in patients
      with HCC and healthy age-matched controls was determined, and correlated with
      plasma alanine transaminase activity (ALT) and bilirubin levels preoperatively
      and on days 1 and 7 postoperation. Correlations between plasma miR-122 and
      clinicopathological characteristics at 1 day postoperation were also determined.
      RESULTS: This study included 80 patients with HCC and 80 controls. Baseline
      expression of miR-122 mRNA and ALT in patients with HCC was significantly higher
      than in controls. MiR-122 expression correlated with ALT and bilirubin levels
      preoperatively and on days 1 and 7 postoperatively. In patients with HCC who
      received a block of the first hepatic portal during surgery and those with
      excised tumour size >5 cm, plasma miR-122 expression was significantly increased
      on day 1 postoperatively, compared with expression levels in those who did not
      receive a block and those with smaller tumours. CONCLUSIONS: Plasma miR-122
      expression is correlated with hepatectomy-induced liver injury in patients with
      HCC. Increase in miR-122 expression could be used as an index of such injury
      before and after hepatectomy in these patients.

PMID- 24287930
TI  - Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene
      polymorphisms in Chinese patients.
AB  - OBJECTIVE: To investigate the prevalence and implication of cytochrome P450,
      family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide
      reductase complex, subunit 1 (VKORC1)-1639 G > A polymorphisms in Chinese
      patients receiving warfarin therapy. METHODS: Chinese Han patients requiring oral
      warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2,
      *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international
      normalized ratios (INRs) and warfarin maintenance dose were investigated.
      RESULTS: Out of 101 patients, there were no significant differences in fourth-day
      INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and
      CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher
      fourth-day INR (1.87 +/- 0.14) than those with the VKORC1-1639 AG genotype (1.32
      +/- 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA
      genotype (2.40 +/- 0.70 mg/day) was significantly lower than for patients with
      the VKORC1-1639 AG genotype (4.83 +/- 0.70 mg/day). CONCLUSIONS: Unlike Caucasian
      populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the
      dominant genetic factors associated with warfarin response variability.

PMID- 24287931
TI  - Development and characterization of a recombinant infectious bronchitis virus
      expressing the ectodomain region of S1 gene of H120 strain.
AB  - Infectious bronchitis (IB), caused by infectious bronchitis virus (IBV), is a
      highly contagious chicken disease, and can lead to serious economic losses in
      poultry enterprises. The continual introduction of new IBV serotypes requires
      alternative strategies for the production of timely and safe vaccines against the
      emergence of variants. Modification of the IBV genome using reverse genetics is
      one way to generate recombinant IBVs as the candidates of new IBV vaccines. In
      this study, the recombinant IBV is developed by replacing the ectodomain region
      of the S1 gene of the IBV Beaudette strain with the corresponding fragment from
      H120 strain, designated as rBeau-H120(S1e). In Vero cells, the virus proliferates
      as its parental virus and can cause syncytium formation. The peak titer would
      reach 10(5.9) 50% (median) tissue culture infective dose/mL at 24 h post
      infection. After inoculation of chickens with the recombinant virus, it
      demonstrated that rBeau-H120(S1e) remained nonpathogenic and was restricted in
      its replication in vivo. Protection studies showed that vaccination with rBeau
      H120 (S1e) at 7-day after hatch provided 80% rate of immune protection against
      challenge with 10(3) 50% embryos infection dose of the virulent IBV M41 strain.
      These results indicate that rBeau-H120 (S1e) has the potential to be an
      alternative vaccine against IBV based on excellent propagation property and
      immunogenicity. This finding might help in providing further information that
      replacement of the ectodomain fragment of the IBV Beaudette S1 gene with that
      from a present field strain is promising for IBV vaccine development.

PMID- 24287932
TI  - Functional rigidity of a methane biofilter during the temporal microbial
      succession.
AB  - Temporal microbial succession was investigated in relation to the performance of
      a methane biofilter. A laboratory-scale biofilter packed with perlite was
      operated for 108 days, without a deliberate biomass control. The system
      performance was stable over the period with a mean elimination capacity of 1,563
      g m(-3) day(-1), despite a temporal deterioration (45-56 days). Ribosomal-tag
      pyrosequencing showed that bacterial communities at days 14-28 were distinct from
      those of days 68-108. The accumulation of nonviable substances strongly coincided
      with the community change (R (2) > 0.97). Rhodobacter, Hydrogenophaga, and
      Methylomonas were dominated in the earlier period, while Methylocaldum and
      Methylococcus were abundant in the later period. The methanotrophic proportion
      gradually increased to 41 %, and type I methanotrophs became predominant over
      time. However, community structure and methanotrophic population density stably
      retained over time, allowing the system to keep the similar performance.
      Therefore, the perlite biofilter system was functionally rigid against the
      temporal microbial succession.

PMID- 24287933
TI  - Monitoring bacterial growth using tunable resistive pulse sensing with a pore
      based technique.
AB  - A novel bacterial growth monitoring method using a tunable resistive pulse sensor
      (TRPS) system is introduced in this study for accurate and sensitive measurement
      of cell size and cell concentration simultaneously. Two model bacterial strains,
      Bacillus subtilis str.168 (BSU168) and Escherichia coli str.DH5alpha (DH5alpha),
      were chosen for benchmarking the growth-monitoring performance of the system.
      Results showed that the technique of TRPS is sensitive and accurate relative to
      widely used methods, with a lower detection limit of cell concentration
      measurement of 5 * 105 cells/ml; at the same time, the mean coefficient of
      variation from TRPS was within 2 %. The growth of BSU168 and DH5alpha in liquid
      cultures was studied by TRPS, optical density (OD), and colony plating. Compared
      to OD measurement, TRPS-measured concentration correlates better with colony
      plating (R = 0.85 vs. R = 0.72), which is often regarded as the gold standard of
      cell concentration determination. General agreement was also observed by
      comparing TRPS-derived cell volume measurements and those determined from
      microscopy. We have demonstrated that TRPS is a reliable method for bacterial
      growth monitoring, where the study of both cell volume and cell concentration are
      needed to provide further details about the physical aspects of cell dynamics in
      real time.

PMID- 24287934
TI  - Enhanced production of polyhydroxyalkanoates (PHAs) from beechwood xylan by
      recombinant Escherichia coli.
AB  - Microbial conversion of plant biomass to value-added products is an attractive
      option to address the impacts of petroleum dependency. In this study, a bacterial
      system was developed that can hydrolyze xylan and utilize xylan-derived xylose
      for growth and production of polyhydroxyalkanoates (PHAs). A beta-xylosidase and
      an endoxylanase were engineered into a P(LA-co-3HB)-producing Escherichia coli
      strain to obtain a xylanolytic strain. Although PHA production yields using xylan
      as sole carbon source were minimal, when the xylan-based media was supplemented
      with a single sugar (xylose or arabinose) to permit the accumulation of xylan
      derived xylose in the media, PHA production yields increased up to 18-fold when
      compared to xylan-based production, and increased by 37 % when compared to
      production from single sugar sources alone. 1H-Nuclear magnetic resonance (NMR)
      analysis shows higher accumulation of xylan-derived xylose in the media when
      xylan was supplemented with arabinose to prevent xylose uptake by catabolite
      repression. 1H-NMR, gel permeation chromatography, and differential scanning
      calorimetry analyses corroborate that the polymers maintain physical properties
      regardless of the carbon source. This study demonstrates that accumulation of
      biomass-derived sugars in the media prior to their uptake by microbes is an
      important aspect to enhance PHA production when using plant biomass as feedstock.

PMID- 24287935
TI  - Bifidobacteria: their impact on gut microbiota composition and their applications
      as probiotics in infants.
AB  - This review is aimed at describing the most recent advances in the gut microbiota
      composition of newborns and infants with a particular emphasis on bifidobacteria.
      The newborn gut microbiota is quite unstable, whereas after weaning, it becomes
      more stable and gets closer to the typical adult microbiota. The newborn and
      infant gut microbiota composition is impaired in several enteric and non-enteric
      pathologies. The core of this review is the description of the most recent
      documented applications of bifidobacteria to newborns and infants for their
      prevention and treatment. Acute diarrhea is the most studied disease for which
      bifidobacteria are applied with great success, Bifidobacterium longum and
      Bifidobacterium breve being the most applied species. Moreover, the most recent
      updates in the use of bifidobacteria for the prevention and treatment of
      pathologies typical of newborns, such as necrotizing enterocolitis, colics, and
      streptococcal infections, are presented. In addition, a number of not strictly
      enteric pathologies have in recent years evidenced a strict correlation with an
      aberrant gut microbiota in infants, in particular showing a reduced level of
      bifidobacteria. These diseases represent new potential opportunities for
      probiotic applications. Among them, allergic diseases, celiac disease, obesity,
      and neurologic diseases are described in this review. The preliminary use of
      bifidobacteria in in vitro systems and animal models is summarized as well as
      preliminary in vivo studies. Only after validation of the results via human
      clinical trials will the potentiality of bifidobacteria in the prevention and
      cure of these pathologies be definitely assessed. 

PMID- 24287936
TI  - Synthesis, purification and mass spectrometric characterisation of a fluorescent
      Au9@BSA nanocluster and its enzymatic digestion by trypsin.
AB  - Nanoclusters of noble metals like Ag and Au have attracted great attention as
      they form a missing link between isolated metal atoms and nanoparticles. Their
      particular properties like luminescence in the visible range and nontoxicity make
      them attractive for bioimaging and biolabelling purposes, especially with use of
      proteins as stabilising agents. In this context, this study intends the synthesis
      of a specific Au nanocluster covered by bovine serum albumin (BSA). It is shown
      that size-exclusion chromatography is feasible for the purification and isolation
      of the nanocluster. A mass spectrometric characterisation, preferably by ESI-MS,
      indicates the presence of an Au9@BSA nanocluster. Enzymatic digestion of the
      nanocluster with trypsin results in a significant increase of the fluorescence
      intensity at 650 and 710 nm, whereas complementary MALDI-MS studies are presented
      for the identification of generated peptides and show a distinctive pattern in
      comparison to the pure protein. It can be concluded that Au9@BSA might be, in
      future, an interesting candidate for in vitro studies of protease activities. 

PMID- 24287937
TI  - Long-term oral therapy with valganciclovir in patients with Posner-Schlossman
      syndrome.
AB  - BACKGROUND: To assess the short-term and long-term efficacy of oral therapy with
      valganciclovir in patients with Posner-Schlossman Syndrome (PSS). METHODS: This
      is a retrospective observational study on 11 patients with PSS treated with
      valganciclovir. The PSS was diagnosed clinically on the basis of recurrent
      episodes of anterior uveitis associated with attacks of elevated intraocular
      pressure (IOP). All patients who did not respond to aciclovir, or whose
      cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) analysis of the aqueous
      humour was positive, were treated with valganciclovir (Valcyte(r)). Initially,
      the drug was given 900 mg twice daily for 3 weeks, followed by 450 mg twice daily
      for a mean period of 20 months (range 10-46 months). RESULTS: Eleven patients
      with mean age of 44 years were included in this study. Four of 11 patients were
      working in a sanitary profession. Before initiation of valgancicloivir therapy,
      the highest IOP was 68 mmHg (mean 45 mmHg +/-9 mmHg). In the first week of
      treatment, the IOP decreased significantly (mean 16 mmHg +/-10 mmHg) and
      maintained stability during the entire treatment period. In seven of 11 (63.6 %)
      patients, valganciclovir led to resolution of inflammatory activity and stable
      IOP. In six patients, the therapy could be discontinued after a mean of 14
      months. However, two patients had a recurrence after discontinuation of
      valganciclovir treatment. No side effects of therapy were observed. CONCLUSIONS:
      Long-term oral therapy with valganciclovir seems to lower the recurrence rate in
      patients with clinically diagnosed PSS.

PMID- 24287938
TI  - The clinical features, management and prognostic effects of pathological
      fractures in a multicenter series of 373 patients with diffuse large B-cell
      lymphoma of the bone.
AB  - BACKGROUND: Pathological fractures (PFs) occur in 10%-20% of patients with
      diffuse large B-cell lymphoma (DLBCL) of the bone. The clinical features and the
      effects of this severe complication on management and prognosis have not been
      previously analyzed in a large series. PATIENTS AND METHODS: The effects of PF on
      management and prognosis were reviewed in an international retrospective series
      of 373 patients with newly diagnosed bone DLBCL, comparing 78 patients with PF at
      presentation (group 'PF-BL') and 295 patients without PF ('controls'). RESULTS:
      At a median follow-up of 53 months (range 3-246), PF-BL patients exhibited lower
      rates of overall response (ORR, 78% versus 85%; P = 0.17), 5-year progression
      free survival (PFS, 53 +/- 6% versus 61 +/- 3%; P = 0.02) and 5-year overall
      survival (OS, 54 +/- 6% versus 68 +/- 3%, P = 0.008) than controls. Initial
      surgical stabilization of the PF did not change therapeutic outcome (5-year OS:
      45 +/- 9% versus 54 +/- 10%; P = 0.20). PF-BL patients referred to irradiation of
      the fractured bone before chemotherapy exhibited a significantly poorer outcome
      than patients managed with the inverse sequence (ORR: 52% versus 92%, P = 0.0005;
      5-year OS: 22 +/- 14% versus 64 +/- 9%, P = 0.007). Multivariate analysis
      confirmed the independent association between PF and worse survival and the
      negative effect of radiotherapy as initial therapy. CONCLUSION: Fracture is an
      independent, adverse prognostic event in patients with bone DLBCL. Anthracycline
      based chemotherapy followed by radiotherapy seems to be the better treatment
      sequence. Initial fracture stabilization does not seem to improve outcome; it
      should be used to improve patient's quality of life only if chemotherapy delays
      can be avoided.

PMID- 24287939
TI  - Prognostic factors for recurrence after conservative treatment in a series of 119
      patients with stage I serous borderline tumors of the ovary.
AB  - BACKGROUND: The aim of this study was to evaluate prognostic factors for
      recurrence after conservative treatment of a large series of 'apparent' stage I
      serous borderline ovarian tumors (SBOTs). PATIENTS AND METHODS: A review of 119
      patients treated conservatively between 2000 and 2009 with follow-up data. All
      pathological slides were reviewed by the same expert pathologist. Prognostic
      factors for recurrence were studied (age, histological subtypes and surgical
      procedure). RESULTS: Conservative surgical procedures were: unilateral cystectomy
      (n = 43, 36%); unilateral adnexectomy (UA; n = 50, 42%); bilateral cystectomies
      (n = 11, 9%) and UA + contralateral cystectomy (n = 15, 13%). Stromal
      microinvasion and/or a micropapillary pattern was present in 21 (18%) and 13
      (11%) patients, respectively. With a median follow-up of 45 months, 38 (32%)
      patients relapsed (10 also had peritoneal disease in the form of noninvasive
      implants at the first recurrence). In 2 of these 38 patients, progression-to
      invasive disease occurred at the second and third relapse (one patient died to
      the recurrence). Three prognostic factors for recurrence were identified in the
      univariate analysis: a young age (< or >30 years old), the type of conservative
      treatment (adnexectomy versus cystectomy) and tumor bilaterality. In the
      multivariate analysis, only age remained statistically significant. CONCLUSION:
      In this series (the largest reported, to date, on recurrences after the
      conservative management of stage I SBOT), the risk of relapse was not related to
      tumor histological subtypes (micropapillary and stromal microinvasion) nor to the
      use of complete staging surgery. Invasive recurrences were very rare in stage I
      SBOT, but did occur. A young age, tumor bilaterality and the use of a cystectomy
      were identified as risk factors for recurrence, suggesting that management of
      fertility preservation (particularly in very young patients) should be associated
      with a meticulously conducted follow-up.

PMID- 24287941
TI  - Involvement of caspase-2 activation in aurora kinase inhibitor-induced cell death
      in axin-expressing L929 cells.
AB  - Axin is a multifunctional protein that participates in many cellular events
      including Wnt signaling and cell fate determination. Aurora kinase inhibitor
      (AKI)-induced cell death and cell membrane rupture is facilitated in L929 cells
      expressing axin (L-axin cells) through the activation of poly ADP-ribose
      polymerase (PARP). We observed that caspase-2 activity is required for AKI
      induced cell death. Inhibition of caspase-2 activity suppressed AKI-induced PARP
      activation and mitochondrial dysfunction, resulting in a decrease in AKI-induced
      cell death. When an axin mutant deleted for the glycogen synthase kinase 3beta
      (GSK3beta)-binding domain was expressed in L929 cells (L-DeltaGSK cells), AKI
      induced caspase-2 activation and cell death decreased. AKI treatment reduced the
      expression of a 32-kDa caspase-2 splicing variant (caspase-2S) in most L-axin
      cells, but not in L-DeltaGSK cells. These results suggest that AKI-induced
      caspase-2 activation in L-axin cells might be due to a decrease in the expression
      of caspase-2S, which inhibits caspase-2 activity. In addition, AKI treatment
      failed to activate caspase-8 and treatment with necrostatin inhibited AKI-induced
      cell death in L-axin cells, suggesting that the absence of caspase-8 activation
      might favor necrotic cell death. Axin expression may facilitate AKI-induced
      caspase-2 activation followed by activation of PARP and initiation of the
      necrotic cell death pathway. 

PMID- 24287940
TI  - A comparative study of five centrally acting drugs on the pharmacological
      treatment of obesity.
AB  - CONTEXT: No long-term studies have compared centrally acting drugs for treating
      obesity. OBJECTIVE: To compare the efficacy and safety of diethylpropion (DEP),
      fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in
      promoting weight loss. DESIGN AND SETTING: A prospective, randomized, placebo
      (PCB)-controlled study conducted at a single academic institution. PATIENTS: A
      total of 174 obese premenopausal women. INTERVENTION: Participants randomly
      received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30),
      FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity
      were encouraged. MAIN OUTCOME MEASURES: The primary endpoints were changes in
      body weight and the proportion of women who achieved at least 5% weight loss by
      week 52 in the intent-to-treat population. Other measurements included
      anthropometry, safety, metabolic and cardiovascular parameters. RESULTS: Weight
      loss was greater than PCB (-3.1+/-4.3 kg) with DEP (-10.0+/-6.4 kg; P<0.001), SIB
      (-9.5+/-5.9 kg; P<0.001), FEN (-7.8+/-6.9 kg; P<0.01) and MZD (-7.4+/-4.9 kg;
      P<0.01) but not with FXT (-2.5+/-4.1 kg). Ten (33.3%) women lost?5% of their
      initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%;
      P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and
      10 (35.5%) with FXT. Each medically treated group experienced more adverse events
      compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent
      with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and
      irritability occurred more frequently with DEP and FEN (P=0.02). Significant
      improvements in the depression and anxiety scores, binge-eating episodes and
      quality of life correlated with weight loss. CONCLUSION: The centrally acting
      drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss
      in obese premenopausal women, with a satisfactory benefit-risk profile.

PMID- 24287942
TI  - Critical success factors for physical activity promotion through community
      partnerships.
AB  - OBJECTIVES: To define key factors of effective evidence-based policy
      implementation for physical activity promotion by use of a partnership approach.
      METHODS: Using Parent and Harvey's model for sport and physical activity
      community-based partnerships, we defined determinants of implementation based on
      13 face-to-face interviews with network organisations and 39 telephone interviews
      with partner organisations. Furthermore, two quantitative data-sets (n = 991 and
      n = 965) were used to measure implementation. RESULTS: In total, nine variables
      were found to influence implementation. Personal contact was the most powerful
      variable since its presence contributed to success while its absence led to a
      negative outcome. Four contributed directly to success: political motive, absence
      of a metropolis, high commitment and more qualified staff. Four others resulted
      in a less successful implementation: absence of positive merger effects, exposure
      motive and governance, and dispersed leadership. CONCLUSIONS: Community networks
      are a promising instrument for the implementation of evidence-based policies.
      However, determinants of both formation and management of partnerships influence
      the implementation success. During partnership formation, special attention
      should be given to partnership motives while social skills are of utmost
      importance for the management.

PMID- 24287943
TI  - First detection of OXA-24 carbapenemase-producing Acinetobacter baumannii
      isolates in Bulgaria.
AB  - This report describes the first identification of OXA-24 carbapenemase-producing
      Acinetobacter baumannii isolates from Bulgaria. According to national
      surveillance data A. baumannii along with Pseudomonas aeruginosa are the most
      troublesome microorganisms in hospital environment with high rates of acquired
      carbapenem resistance. In the present study real-time multiplex PCR was performed
      to identify the most common carbapenemase genes in 15 non-duplicate carbapenem
      resistant A. baumannii isolates collected in 2012. The results showed lack of
      KPC, GES, VIM, IMP-type enzymes. Four A. baumannii isolates tested positive by
      PCR for the acquired OXA-24 together with the intrinsic OXA-51 carbapenemase. OXA
      24 and OXA-23 were determined as co-existent in one isolate. Two isolates were
      identified with OXA-23 in addition to the OXA-51 carbapenemase. 

PMID- 24287944
TI  - A feeding strategy for incorporation of canola derived medium-chain-length
      monomers into the PHA produced by wild-type Cupriavidus necator.
AB  - The aim of this study was to increase the density of wild type Cupriavidus
      necator H16 biomass grown on fructose in order to produce sufficient copolymer of
      short-chain-length (scl) and medium-chain-length (mcl) polyhydroxyalkanoate (PHA)
      from canola oil for mechanical testing of the PHA. Initial batch cultivation on
      fructose was followed by exponential feeding of fructose at a predetermined MU to
      achieve 44.4 g biomass/l containing only 20 % w/w of polyhydroxybutyrate (PHB)
      with a Y(x/fructose) of 0.44 g/g. In a third stage, canola oil was added under N
      limited conditions to produce 92 g/l of biomass with 48 % w/w scl-mcl PHA. Using
      known standards, the PHA composition was confirmed by GC-MS analysis as 99.81 % 3
      hydroxybutyrate, 0.06 % 3-hydroxyvalerate, 0.09 % 3-hydroxyhexanoate and 0.04 % 3
      hydroxyoctanoate. The melting temperature (179  degrees C), crystallinity (54 %),
      tensile stress (25.1 Mpa) and Young's modulus (698 Mpa) for a PHB standard
      decreased to 176  degrees C, 52 %, 19.1 and 443 Mpa respectively for C. necator
      PHA produced in the 3-stage process.

PMID- 24287945
TI  - On the effect of the nature of the bridge on oxidative or reductive photoinduced
      electron transfer in donor-bridge-acceptor systems.
AB  - Photoinduced electron transfer is a topical issue in chemistry. In multicomponent
      donor-bridge-acceptor systems, electron transfer is usually discussed within the
      frame of superexchange theory, which takes into account electronic coupling
      mediated by virtual states involving bridge orbitals. However, the schematization
      used for superexchange in thermal electron transfer processes is not suitable to
      immediately understand some intriguing aspects of photoinduced charge separation
      and recombination processes, which are only uncovered by analyzing the virtual
      states involved in forward and backward excited-state electron transfer. In
      particular, for oxidative photoinduced electron transfer, a low-energy virtual
      state which cannot mediate the forward charge separation can efficiently mediate
      charge recombination via the hole-transfer superexchange route, whereas for
      reductive photoinduced electron transfer, a low-energy virtual state which cannot
      mediate the forward process can efficiently mediate charge recombination via
      electron-transfer superexchange. As a consequence, to obtain long-lived charge
      separated states upon oxidative photoinduced electron transfer in donor-bridge
      acceptor systems it is preferable to avoid easy-to-oxidize bridges, whereas easy
      to-reduce bridges should better be avoided in reductive photoinduced charge
      separation. These considerations, exemplified by the analysis of some literature
      cases, can be useful hints for the design of long-lived charge-separated states. 

PMID- 24287946
TI  - Phenolic responses of mountain crowberry (Empetrum nigrum ssp. hermaphroditum) to
      global climate change are compound specific and depend on grazing by reindeer
      (Rangifer tarandus).
AB  - Mountain crowberry (Empetrum nigrum ssp. hermaphroditum) is a keystone species in
      northern ecosystems and exerts important ecosystem-level effects through high
      concentrations of phenolic metabolites. It has not been investigated how
      crowberry phenolics will respond to global climate change. In the tundra, grazing
      by reindeer (Rangifer tarandus) affects vegetation and soil nutrient
      availability, but almost nothing is known about the interactions between grazing
      and global climate change on plant phenolics. We performed a factorial warming
      and fertilization experiment in a tundra ecosystem under light grazing and heavy
      grazing and analyzed individual foliar phenolics and crowberry abundance.
      Crowberry was more abundant under light grazing than heavy grazing. Although
      phenolic concentrations did not differ between grazing intensities, responses of
      crowberry abundance and phenolic concentrations to warming varied significantly
      depending on grazing intensity. Under light grazing, warming increased crowberry
      abundance and the concentration of stilbenes, but decreased e.g., the
      concentrations of flavonols, condensed tannins, and batatasin-III, resulting in
      no change in total phenolics. Under heavy grazing, warming did not affect
      crowberry abundance, and induced a weak but consistent decrease among the
      different phenolic compound groups, resulting in a net decrease in total
      phenolics. Our results show that the different phenolic compound groups may show
      varying or even opposing responses to warming in the tundra at different levels
      of grazing intensity. Even when plant phenolic concentrations do not directly
      respond to grazing, grazers may have a key control over plant responses to
      changes in the abiotic environment, reflecting multiple adaptive purposes of
      plant phenolics and complex interactions between the biotic and the abiotic
      factors. 

PMID- 24287947
TI  - Reduced expression of Slit2 in renal cell carcinoma.
AB  - Slit2, initially identified as an important axon guidance molecule in the nervous
      system, was suggested to be involved in multiple cellular processes. Recently,
      Slit2 was reported to function as a potential tumor suppressor in diverse tumors.
      In this study, we systematically analyzed the expression level of Slit2 in renal
      cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2
      mRNA and protein expression were significantly down-regulated in renal cell
      carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was
      methylated in two renal carcinoma cell lines. Pharmacologic demethylation
      dramatically induced Slit2 expression in cancer cell lines with weak expression
      of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation
      existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation
      was observed in 8 out of 38 patients (21.1 %), which was well correlated with the
      down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor
      suppressor in RCC, which is down-regulated in RCC partially due to promoter
      methylation.

PMID- 24287948
TI  - Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han
      population.
AB  - Glioma is the most common type of primary brain malignancy in adults. The anti
      apoptotic protein B-cell lymphoma 2 (BCL2) has been implicated in the
      pathogenesis of glioma. This study aimed to evaluate the potential association
      between BCL2-938C>A genetic polymorphism and glioma susceptibility. This case
      control study was conducted in Chinese Han populations consisting of 248 glioma
      cases and 252 cancer-free controls. The BCL2-938C>A genetic polymorphism was
      detected by the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data
      suggested that the genotype/allele of BCL2-938C>A polymorphism were statistically
      associated with the increased risk of glioma where the risk of glioma for
      genotype AA or allele A is significantly higher than wild genotype CC (odds ratio
      (OR) = 2.23, 95% confidence interval (CI) 1.21-4.10, p = 0.009) or allele C (OR =
      1.39, 95% CI 1.06-1.82, p = 0.016), respectively. In addition, the BCL2-938AA
      genotype was significantly more common in patients with glioblastoma and in
      patients with grade IV glioma. Our findings indicate that the BCL2-938C>A
      polymorphism is associated with the susceptibility to glioma in Chinese Han
      populations and might be used as molecular markers for evaluating glioma risk.

PMID- 24287949
TI  - Anti-hepatoma cells function of luteolin through inducing apoptosis and cell
      cycle arrest.
AB  - The aim of this study is to explore the apoptotic induction and cell cycle arrest
      function of luteolin on the liver cancer cells and the related mechanism. The
      liver cancer cell line SMMC-7721, BEL-7402, and normal liver cells HL-7702 were
      treated with different concentrations of luteolin. Cell proliferation ability was
      tested. Morphological changes of the apoptotic cells were observed under inverted
      fluorescence microscope after Hoechst33342 staining. We investigated the effect
      of luteolin on cell cycling and apoptosis with flow cytometry. The mitochondrial
      membrane potential changes were analyzed after JC-1 staining. Caspases-3 and Bcl
      2 family proteins expression were analyzed by real-time PCR. Cell proliferation
      of SMMC-7721 and BEL-7402 were inhibited by luteolin, and the inhibition was dose
      time-dependent. Luteolin could arrest the cells at G1/S stage, reduce
      mitochondrial membrane potential, and induce higher apoptosis rate and the
      typical apoptotic morphological changes of the liver carcinoma cells. Q-RT-PCR
      results also showed that luteolin increased Bax and caspase-3 expression
      significantly and upregulated Bcl-2 expression in a dose-dependent manner in
      liver carcinoma cells. However, the normal liver cells HL-7702 was almost not
      affected by luteolin treatment. Luteolin can inhibit SMMC-7721 and BEL-7402 cell
      proliferation in a time- and dose-dependent manner. And the mechanism maybe
      through arresting cell cycle at phase G1/S, enhancing Bax level, reducing anti
      apoptotic protein Bcl-2 level, resulting in activating caspase-3 enzyme and
      decrease of mitochondrial membrane potential, and finally leading to cell
      apoptosis. 

PMID- 24287950
TI  - Association of RECQL5 gene polymorphisms and osteosarcoma in a Chinese Han
      population.
AB  - Despite the knowledge on many genetic variants present in osteosarcoma, the
      complexity of this disease precludes placing its biology into a simple conceptual
      framework. RECQL is a DNA helicase involved in DNA mismatch repair and has been
      reported to be associated with many human cancers. We aimed to investigate the
      association of RECQL genetic polymorphism with osteosarcoma in a Chinese
      population. We selected three polymorphisms of the RECQL5 gene (rs820196,
      rs820200, and rs4789223) in the present study. TaqMan method was utilized for
      genotyping these three SNPs in 212 patients with osteosarcoma and 240 age- and
      sex-matched noncancer controls. In our study, we found that CC genotype in
      rs820196 (17.5 vs 8.3%, P = 0.005) and AA genotype in rs4789223 (21.7 vs 14.2, P
      < 0.001) were more frequent in osteosarcoma group compared to the control group,
      respectively. We also found that the C allele of rs820196 (OR = 1.492, 95% CI
      1.138 ~ 1.951; P = 0.004) and A allele of rs4789223 (OR = 1.767, 95% CI: 1.354 ~
      2.301; P < 0.001) were common in the osteosarcoma patients than those in the
      control subjects, respectively. Haplotype analysis showed that TTA (OR = 3.469,
      95% CI 1.798 ~ 6.695; P < 0.001) was associated with increased risk for
      osteosarcoma. However, the TTG (OR = 0.578, 95% CI 0.442 ~ 0.756) was associated
      with decreased risk for osteosarcoma. Our results suggested that RECQL5 genetic
      polymorphisms were associated with osteosarcoma in a Chinese population.

PMID- 24287952
TI  - Data mining approaches to high-throughput crystal structure and compound
      prediction.
AB  - Predicting unknown inorganic compounds and their crystal structure is a critical
      step of high-throughput computational materials design and discovery. One way to
      achieve efficient compound prediction is to use data mining or machine learning
      methods. In this chapter we present a few algorithms for data mining compound
      prediction and their applications to different materials discovery problems. In
      particular, the patterns or correlations governing phase stability for
      experimental or computational inorganic compound databases are statistically
      learned and used to build probabilistic or regression models to identify novel
      compounds and their crystal structures. The stability of those compound
      candidates is then assessed using ab initio techniques. Finally, we report a few
      cases where data mining driven computational predictions were experimentally
      confirmed through inorganic synthesis. 

PMID- 24287951
TI  - Lack of association between MTHFD1 G401A polymorphism and ovarian cancer
      susceptibility.
AB  - Published studies on the association between methylenetetrahydrofolate
      dehydrogenase 1 (MTHFD1) G401A polymorphism and ovarian cancer risk have yielded
      conflicting results. In order to derive a more precise estimation of the
      relationship between G401A polymorphism and ovarian cancer risk, the present meta
      analysis was performed. All eligible studies on G401A polymorphism and ovarian
      cancer risk were collected from the PubMed and the Cochrane Library. Statistical
      analyses were performed by Review Manage 5.0 and Stata 11.0. Our analysis
      suggested that G401A polymorphism was not associated with ovarian cancer risk
      when using additive (odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.34
      2.20, P < 0.0001), recessive (OR = 1.46, 95% CI = 1.21-1.77, P < 0.0001),
      dominant (OR = 1.36, 95% CI = 1.10-1.69, P = 0.004), and allelic models (OR =
      1.30, 95% CI = 1.15-1.47, P < 0.0001) to analyze the data. This meta-analysis
      suggests that G401A polymorphism might not be a risk factor for ovarian cancer
      risk. However, further well-designed studies are required to confirm our
      findings.

PMID- 24287953
TI  - Aortic valve replacement within an unexpected porcelain aorta: the sutureless
      valve option.
AB  - Four patients referred for surgical treatment of aortic stenosis presented an
      unexpected extremely calcified (porcelain) ascending aorta at the intraoperative
      epiaortic ultrasonography scanning. In each patient, replacement of the aortic
      valve was successfully performed using a sutureless implantable bioprosthesis
      during a short period of hypothermic circulatory arrest. In the era of
      transcatheter aortic valve implantation procedures, the sutureless valve may be a
      valuable option for surgical units that do not dispose of transcatheter
      technology or a hybrid operative theatre. 

PMID- 24287954
TI  - Spontaneous regression of thymic epithelial tumours.
AB  - We herein report the cases of 3 patients with thymic epithelial tumours,
      including two thymomas and a carcinoma, where the tumours spontaneously regressed
      in size. The patients were all female ranging in age from 32 to 43 years. During
      1 or 2 months without any treatment, the tumours regressed by 25-59% in size. The
      pleural effusion observed in 2 patients also disappeared during the same period.
      Pathological examinations revealed areas of necrosis or cystic changes within the
      two thymomas. Among the patients with thymic epithelial tumours, the existence of
      this rare disease entity must be recognized. 

PMID- 24287955
TI  - Shellfish toxins targeting voltage-gated sodium channels.
AB  - Voltage-gated sodium channels (VGSCs) play a central role in the generation and
      propagation of action potentials in excitable neurons and other cells and are
      targeted by commonly used local anesthetics, antiarrhythmics, and
      anticonvulsants. They are also common targets of neurotoxins including shellfish
      toxins. Shellfish toxins are a variety of toxic secondary metabolites produced by
      prokaryotic cyanobacteria and eukaryotic dinoflagellates in both marine and fresh
      water systems, which can accumulate in marine animals via the food chain.
      Consumption of shellfish toxin-contaminated seafood may result in potentially
      fatal human shellfish poisoning. This article provides an overview of the
      structure, bioactivity, and pharmacology of shellfish toxins that act on VGSCs,
      along with a brief discussion on their pharmaceutical potential for pain
      management. 

PMID- 24287956
TI  - Toxic c17-sphinganine analogue mycotoxin, contaminating tunisian mussels, causes
      flaccid paralysis in rodents.
AB  - Severe toxicity was detected in mussels from Bizerte Lagoon (Northern Tunisia)
      using routine mouse bioassays for detecting diarrheic and paralytic toxins not
      associated to classical phytoplankton blooming. The atypical toxicity was
      characterized by rapid mouse death. The aim of the present work was to understand
      the basis of such toxicity. Bioassay-guided chromatographic separation and mass
      spectrometry were used to detect and characterize the fraction responsible for
      mussels' toxicity. Only a C17-sphinganine analog mycotoxin (C17-SAMT), with a
      molecular mass of 287.289 Da, was found in contaminated shellfish. The doses of
      C17-SAMT that were lethal to 50% of mice were 750 and 150 MUg/kg following
      intraperitoneal and intracerebroventricular injections, respectively, and 900
      MUg/kg following oral administration. The macroscopic general aspect of cultures
      and the morphological characteristics of the strains isolated from mussels
      revealed that the toxicity episodes were associated to the presence of marine
      microfungi (Fusarium sp., Aspergillus sp. and Trichoderma sp.) in contaminated
      samples. The major in vivo effect of C17-SAMT on the mouse neuromuscular system
      was a dose- and time-dependent decrease of compound muscle action potential
      amplitude and an increased excitability threshold. In vitro, C17-SAMT caused a
      dose- and time-dependent block of directly- and indirectly-elicited isometric
      contraction of isolated mouse hemidiaphragms. 

PMID- 24287957
TI  - The oldest known communal latrines provide evidence of gregarism in Triassic
      megaherbivores.
AB  - Defecation in communal latrines is a common behaviour of extant mammals widely
      distributed among megaherbivores. This behaviour has key social functions with
      important biological and ecological implications. Herbivore communal latrines are
      only documented among mammals and their fossil record is exceptionally restricted
      to the late Cenozoic. Here we report the discovery of several massive coprolite
      associations in the Middle-Late Triassic of the Chanares Formation, Argentina,
      which represent fossil communal latrines based on a high areal density, small
      areal extension and taphonomic attributes. Several lines of evidence (size,
      morphology, abundance and coprofabrics) and their association with
      kannemeyeriiform dicynodonts indicate that these large synapsids produced the
      communal latrines and had a gregarious behaviour comparable to that of extant
      megaherbivores. This is the first evidence of megaherbivore communal latrines in
      non-mammal vertebrates, indicating that this mammal-type behaviour was present in
      distant relatives of mammals, and predates its previous oldest record by 220 Mya.

PMID- 24287958
TI  - Adenoidectomy as an adjuvant to primary tympanostomy tube placement: a systematic
      review and meta-analysis.
AB  - IMPORTANCE: Adenoidectomy at initial tympanostomy tube placement (TT) may reduce
      the rate of repeated surgery for otitis media. OBJECTIVE: To assess the
      effectiveness of primary adenoidectomy as an adjuvant to TT (Ad + TT) compared
      with TT alone. DATA SOURCES: PubMed and EMBASE electronic databases were searched
      with no publication year restrictions beyond those of the individual databases.
      STUDY SELECTION: Articles that compared outcomes of children having undergone
      primary Ad + TT with children having undergone TT alone for middle ear disease.
      DATA EXTRACTION: Medical literature addressing Ad + TT was systematically
      reviewed. Data extracted included study design, age of children, and follow-up
      time frame. Level of evidence was assessed, and data were pooled where possible.
      MAIN OUTCOMES AND MEASURES: Proportion of children requiring repeated TT (r-TT).
      Secondary outcomes included proportion of children with recurrent acute otitis
      media (RAOM), otitis media with effusion (OME), otorrhea, or any combination of
      the 3. RESULTS: Fifteen articles met inclusion criteria. Ten studies (n = 71,353)
      reported that primary Ad + TT decreased the risk of r-TT or risk of RAOM, OME, or
      otorrhea compared with TT alone. Four studies (n = 538) reported no difference
      between Ad + TT groups compared with TT-only groups in the prevention of r-TT or
      of RAOM, OME, or otorrhea. Despite significant heterogeneity, limited meta
      analysis and pooling of data revealed that the estimated rate of r-TT for
      children undergoing primary adenoidectomy was 17.2% (95% CI, 12.2%-22.2%) vs
      31.8% (95% CI, 23.9%-39.8%) for children undergoing primary TT only. When
      stratified by age younger than 4 years, the protective effects of adenoidectomy
      were diminished. CONCLUSIONS AND RELEVANCE: The current evidence suggests that
      primary Ad + TT may be superior to TT only in decreasing the risk of r-TT and the
      risk of RAOM, OME, or otorrhea. Limitations include heterogeneity of the source
      data, with the predominance of retrospective data as well as studies with older
      children supporting the superiority of adjuvant adenoidectomy. The practice of Ad
      + TT may decrease the risk of repeated surgery in children older than 4 years.

PMID- 24287959
TI  - Patellar calcar: MRI appearance of a previously undescribed anatomical entity.
AB  - OBJECTIVE: The femoral calcar is a constant anatomical structure within the
      proximal femur representing a condensation of bone trabeculae. It is our
      impression that a similar structure is present within the patella. The purpose of
      this retrospective study was to define the prevalence, appearance, location, and
      configuration of the patellar calcar on MRI examinations. MATERIALS AND METHODS:
      One hundred consecutive unenhanced knee MRIs were retrospectively reviewed by two
      readers who were blinded to the clinical indication. The patellar calcar was
      defined as a dark signaling, linear or curvilinear structure subjacent to the
      patellar articular surface. If present, the patellar calcar was assigned to a
      "well seen," "moderately well seen," or "faintly seen" category. Location of the
      calcar within the patella, orientation, configuration, and thickness were
      recorded. Confounding variables, such as marrow edema, patellar chondromalacia,
      bipartite patella, or postoperative changes were also recorded. RESULTS: The
      patellar calcar was visualized in 81 out of 100 (81 %) MRIs. When detected, the
      calcar was well seen in 20 out of 81 (25 %), moderately well seen in 35 out of 81
      (43 %), and faintly seen in 26 out of 81 (32 %). The anteroposterior width of the
      calcar measured at its thickest segment was: < 1 mm in 43 out of 81 (53 %), 1 mm
      in 28 out of 81 (35 %), and >1 mm in 10 out of 81 (12 %). CONCLUSION: The
      patellar calcar was seen in the majority of knee MRIs and had a consistent
      imaging appearance. The calcar may be obscured by degenerative arthrosis of the
      patella and rarely may mimic patellar stress fracture or osteochondritis
      dissecans. Radiologists and clinicians should be familiar with this normal
      anatomical structure.

PMID- 24287960
TI  - Considerations on the calculation of fractions of cardiovascular disease
      attributable to psychosocial work factors : comment on: Niedhammer I, Sultan
      Taieb H, Chastang JF, Vermeylen G, Parent-Thirion A. Fractions of cardiovascular
      diseases and mental disorders attributable to psychosocial work factors in 31
      countries in Europe.

PMID- 24287961
TI  - Response to the letter to the editor by Latza et al.: Indirect evaluation of
      attributable fractions for psychosocial work exposures: a difficult research
      area.

PMID- 24287962
TI  - Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and
      psychological variables.
AB  - This retrospective study investigated, in two cohorts of subjects living in
      Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC),
      the variables related to diagnostic delay ascribable to the patient, with
      particular reference to the cognitive and psychological ones. A total of 156
      patients with OSCC (mean age: 62 years, M/F: 2.39?1) were recruited at the
      Universities of Palermo and Naples. Risk factors related to patient delay
      included: sociodemographic, health-related, cognitive and psychological
      variables. The analysis was conducted by considering two different delay ranges:
      dichotomous (<=1 month vs. >1 month) and polytomous (<1 month, 1-3 months, >3
      months) delay. Data were investigated by univariate and multivariate analyses and
      a P value <=0.05 was considered statistically significant. For both delay
      measurements, the most relevant variables were: 'Personal experience of cancer'
      (dichotomous delay: P=0.05, odds ratio (OR)=0.33, 95% confidence interval
      (CI)=0.11-0.99; polytomous delay: P=0.006, Chi-square=10.224) and 'Unawareness'
      (dichotomous delay: P<0.01, OR=4.96, 95% CI=2.16-11.37; polytomous delay:
      P=0.087, Chi-square=4.77). Also 'Denial' (P<0.01, OR=6.84, 95% CI=2.31-20.24) and
      'Knowledge of cancer' (P=0.079, Chi-square=8.359) were found to be statistically
      significant both for dichotomous and for polytomous categorization of delay,
      respectively. The findings of this study indicated that, in the investigated
      cohorts, the knowledge about cancer issues is strongly linked to the patient
      delay. Educational interventions on the Mediterranean population are necessary in
      order to increase the patient awareness and to emphasize his/her key role in
      early diagnosis of OSCC. 

PMID- 24287963
TI  - Australian gay men's satisfaction with sexual agreements: the roles of
      relationship quality, jealousy, and monogamy attitudes.
AB  - This study examined whether relationship quality, dispositional jealousy, and
      attitudes towards monogamy were associated with gay men's satisfaction with the
      agreements they have in their relationships about extra-dyadic sex. Three types
      of sexual agreement were examined: closed (no extra-dyadic sex is allowed),
      monogamish (extra-dyadic sex is allowed only when both members of the couple are
      present), and open (extra-dyadic sex is allowed). Results from a 2010 survey of
      772 gay men in relationships indicated that sexual agreement satisfaction was
      positively associated with levels of intimacy and commitment for all three types
      of sexual agreement, but was differentially associated with sexual satisfaction
      within the relationship, jealousy, and monogamy attitudes as a function of sexual
      agreement type. Mean levels of sexual satisfaction, jealousy, and monogamy
      attitudes also differed between types of agreement. These findings provided
      preliminary evidence that sexual agreement satisfaction may be influenced by
      different factors depending on the type of agreement, which has useful
      implications for professionals with gay male clients experiencing dissatisfaction
      with their agreement or with their relationship more generally. 

PMID- 24287964
TI  - Response to Bayesian advice for gaydar-based picking up: commentary on Lyons,
      Lynch, Brewer, and Bruno (2013) by Ploderl.

PMID- 24287965
TI  - What's love got to do with it? Examinations of emotional perceptions and sexual
      behaviors among gay and bisexual men in the United States.
AB  - Men who have sex with men (MSM) continue to be disproportionately impacted by
      STIs and HIV. In addition to traditional risk factors, increasing attention has
      been given to the potential role of affective components of a sexual encounter,
      including mood state. To date, no study has described sexual behaviors engaged in
      by those who report being in love (or not) during a given sexual event. Internet
      based survey data were collected from 24,787 gay and bisexual men who were
      members of online websites facilitating social or sexual interactions with other
      men. Measures included sociodemographics, recent sexual behavior history, sexual
      event characteristics, and perceptions of "love" with men's most recent male
      sexual partner. Participants' mean age was 39.2 years; ethnicities included white
      (84.6 %), Latino (6.4 %), and African American (3.6 %). Nearly all men (91 %)
      were matched by presence (I love him/he loves me), absence (I don't love him/he
      doesn't love me), or uncertainty (I don't know if I do/I don't know if he does)
      of love with their most recent sexual partner. Men who reported love for their
      partner and believed their partner loved them were significantly more likely to
      have engaged in behaviors such as cuddling and kissing on the mouth. Differences
      were also seen in regard to love and men's reports of anal intercourse and oral
      sex. Findings highlight differences in sexual behaviors based on perceptions of
      love and suggest the need to further explore how these differences influence
      sexual health.

PMID- 24287966
TI  - Between a reactant rock and a solvent hard place--molecular corrals guide
      aromatic substitutions.
AB  - A novel reaction mechanism is presented for an ortho-magnesium carboxylate driven
      aromatic nucleophilic substitution in naphthoic acids, supported by high-level
      density functional theory. Results show that the rate-determining aspects involve
      an R-group transfer from a Grignard reagent Mg-atom to the C1-atom on a
      naphthalene ring. This transfer is moderated by a molecular corral comprised of
      two solvent THF molecules and the naphthoic acid, which collectively marshal the
      R-group into position. The CAM-B3LYP method was employed together with the all
      electron DZVP basis set. Solvent was treated using an implicit dielectric
      continuum (PCM method) and IDSCRF atomic-radii. Further evolved solvent models
      were also investigated, consisting of explicit solvating particles forming a
      primary solvation layer framing the reaction center. Reaction barriers obtained
      are in close agreement with experimental trends, with R-group substituent
      identity tempering repulsion with the molecular corral, in-turn modulating the
      free-energy barriers. Partitioning of the dynamic bases of entropy contribution
      to free-energy was central to the successful experimental-theoretical synergy. 

PMID- 24287967
TI  - Large pore mesostructured cellular silica foam coated magnetic oxide composites
      with multilamellar vesicle shells for adsorption.
AB  - Herein, large pore mesostructured cellular silica foam coated magnetic oxide
      composites (MO@MCFs) with multilamellar vesicle shells (MO@MLVs) were obtained,
      which exhibited a large pore (>10 nm), strong magnetic response (38 emu g(-1)),
      excellent protein adsorption and slow drug-release capacity. 

PMID- 24287968
TI  - A ratiometric and colorimetric luminescent thermometer over a wide temperature
      range based on a lanthanide coordination polymer.
AB  - A lanthanide coordination polymer Tb0.957Eu0.043cpda was synthesized as a
      ratiometric and colorimetric luminescent thermometer. The high triplet excited
      state energy of a linker enables Tb0.957Eu0.043cpda to detect and visualize
      temperature over a wide range from cryogenic to room temperature (40-300 K). 

PMID- 24287969
TI  - Benefit of second catheter angiography in patients with nontraumatic
      subarachnoidal hemorrhage.
AB  - PURPOSE: This study aimed to determine the yield of repetitive catheter
      angiography (digital subtraction angiography (DSA)) for the detection of
      causative vascular lesions in patients with nontraumatic subarachnoidal
      hemorrhage (SAH) and negative initial DSA. We hypothesize that a second DSA might
      be helpful to detect an initially occult bleeding source. METHODS: We
      retrospectively evaluated 649 patients with acute SAH and invasive catheter
      angiographies between 2004 and 2012. In 90 SAH patients initial imaging was
      negative concerning a causative bleeding source. A total of 113 repetitive DSA
      were performed. Two neuroradiologists reanalyzed the initial imaging and the
      result of the reangiography independently. RESULTS: In 4/90 patients (4.5 %)
      bleeding source was first detected in the second or third DSA. In all other
      patients, no causative vascular lesion was found. Reasons for the initially false
      negative diagnostics were one dissecting aneurysm and thrombosis of three
      aneurysms within the acute phase of SAH. CONCLUSIONS: Repetitive DSA revealed the
      cause of SAH in 4.5 % of the cases. These findings have a therapeutic and
      prognostic impact. We think that at least a second DSA should be part of
      diagnostic work-up in patients with SAH and missing bleeding source, even
      considering the risk of an additional invasive angiography itself.

PMID- 24287970
TI  - An interview with Molly S Shoichet. Developing biomaterials and mobilizing
      resources for assaults on some of the most devastating medical problems by Myron
      Spector.

PMID- 24287971
TI  - Fluorescence and HPLC Detection of Hydroxyl Radical by a Rhodamine-Nitroxide
      Probe and its Application in Cell Imaging.
AB  - A rhodamine nitroxide probe was designed to detect the hydroxyl radical (.OH),
      which presented high selectivity for .OH over other reactive oxygen species (ROS)
      and linear fluorescence response to .OH produced by Fenton reaction. The product
      was detected by HPLC-MS, indicating that the main product of the reaction was O
      methylhydroxylamine and the product peak areas measured by HPLC-UV/vis and HPLC
      FLD both enhanced proportionally with the increase of .OH concentration. The
      application of the probe in biological system was explored to trace the
      production of .OH in cells under oxidative stress condition induced by rotenone
      which can inhibit the mitochondria respiratory chain complex I and we found that
      appropriate rotenone may induce the normal human liver cells (L02) and human
      hepatoma cells (HepG2) to produce .OH at different degrees. 

PMID- 24287972
TI  - Interaction of Sulfadiazine with Model Water Soluble Proteins: A Combined
      Fluorescence Spectroscopic and Molecular Modeling Approach.
AB  - The binding behavior of antibacterial drug sulfadiazine (SDZ) with water soluble
      globular proteins like bovine as well as human serum albumin (BSA and HSA,
      respectively) and lysozyme (LYS) was monitored by fluorescence titration and
      molecular docking calculations. The experimental data reveal that the quenching
      of the intrinsic protein fluorescence in presence of SDZ is due to the strong
      interaction in the drug binding site of the respective proteins. The Stern-Volmer
      plot shows positive deviation at higher quencher concentration for all the
      proteins and was explained in terms of a sphere of action model. The calculated
      fluorophore-quencher distances vary within 4 ~ 11 A in different cases.
      Fluorescence experiments at different temperature indicate thermodynamically
      favorable binding of SDZ with the proteins with apparently strong association
      constant (~10(4)-10(5) M(-1)) and negative free energy of interaction within the
      range of -26.0 ~ -36.8 kJ mol(-1). The experimental findings are in good
      agreement with the respective parameters obtained from best energy ranked
      molecular docking calculation results of SDZ with all the three proteins. 

PMID- 24287973
TI  - Overlap of Doxycycline Fluorescence with that of the Redox-Sensitive
      Intracellular Reporter roGFP.
AB  - Tetracycline-inducible systems allow for either suppression or induction of
      transgene expression to facilitate studies of cell physiology. Doxycycline is a
      preferred inducer for these gene expression systems due to its membrane
      permeability; however, the heterocyclic structure of doxycycline exhibits
      fluorogenic properties that can potentially bias measurement of other
      fluorochromes. Thus the simultaneous use of tetracycline-inducible systems and
      fluorescent proteins as reporter genes or as intracellular biosensors may lead to
      potentially confounding results. Herein, using cells which co-express the
      ratiometric redox sensitive intracellular reporter, roGFP, and a tetracycline
      inducible reporter plasmid encoding the reporter gene, mCherry, as a model
      system, we describe the overlapping intracellular fluorescent signals between
      doxycycline and commonly used intracellular fluorescent probes. In our cells, the
      addition of doxycycline to cells caused a dose- and time-dependent increase in
      cell fluorescence with 405 nm excitation which overlapped with that of the
      oxidized configuration of roGFP. Incubating cells in concentrations of
      doxycycline less than 1 MUg/mL and removing doxycycline from the media 60 min
      before performing experiments eliminated fluorescence interference while still
      maintaining maximal reporter transgene activation. 

PMID- 24287974
TI  - Off-on Fluorescent Sensor from On-off Sensor: Exploiting Silver Nanoparticles
      Influence on the Organic Fluorophore Fluorescence.
AB  - Turn-off fluorescence of organic fluorophore, 2-{[4-(2H-Naphtho[1,2
      d][1,2,3]triazol-2-yl)-phenyl]carboxylic acid (NTPC), with metal ions (Fe(3+),
      Cu(2+), Pb(2+)) was converted into turn-on fluorescent sensor for biologically
      important Zn(2+), Cu(2+) and Fe(3+) metal ions in aqueous solution at ppb level
      by exploiting strong fluorescence quenching phenomena of metal nanoparticles when
      organic fluorophores assembled in the vicinity of metallic surface. Amino acid
      attached phenolic ligands (L) were used as reducing as well as functional capping
      agents in the synthesis of silver nanoparticles (AgNPs). The hydrogen bonding
      functionality of L facilitated the assembling of NTPC in the vicinity of metallic
      surfaces that leads to complete quenching of NTPC fluorescence. The strong and
      selective coordination of L with metal ions (Zn(2+), Cu(2+) and Fe(3+)) separates
      the NTPC from the AgNPs surface that turn-on the NTPC fluorescence. HR-TEM and
      absorption studies confirm the metal coordination with L and separation of NTPC
      from the AgNPs surface. Mn(2+) showed selective red shifting of NTPC fluorescence
      after 12 h with all sample. Effects of different amino acid attached phenolic
      ligands were explored in the metal ion sensitivity and selectivity. This approach
      demonstrates the multifunctional utility of metal NPs in the development of turn
      on fluorescence sensor for paramagnetic heavy metal ions in aqueous solution. ?

PMID- 24287975
TI  - A commentary on the relationship between head injury and facial trauma: a case
      control study.

PMID- 24287976
TI  - Effect of platelet-rich plasma on bone regeneration after removal of cysts and
      benign tumours of the jaws.
AB  - INTRODUCTION: Platelets are involved in regeneration at sites of pathology, apart
      from their role in clotting. A preparation composed mainly of platelets (platelet
      rich plasma gel) applied to sites of bony pathology, after surgical treatment of
      lesions, may hasten bone regeneration. MATERIALS AND METHODS: An autologous
      platelet-rich plasma (PRP) gel was prepared using a standardized technique,
      without using thrombin clot accelerator, and applied to surgical site in six
      patients of study group. Five patients were enrolled as controls, in whom PRP gel
      was not used. The differences in the occurrence of radiographic changes between
      the study and control group at 6, 12, 18 and 24 weeks after surgery were analysed
      with chi-square test. Intragroup radiographic changes, i.e. within the study and
      control groups occurring over the 24 weeks of follow-up, were analysed with
      Friedman test. RESULTS: A trend towards more rapid healing was observed in the
      study group at 6, 12, 18 and 24 weeks. However, these differences between the
      study and control group were not statistically significant. Both the study and
      control group demonstrated significant healing changes over the 24 weeks of
      follow-up. CONCLUSIONS: It is possible to prepare platelet-rich plasma gel
      without using thrombin clot accelerator. PRP, as prepared and applied to surgical
      sites in this study, was not observed to significantly enhance bone regeneration.
      All surgical sites, both in the PRP and control group, showed significant healing
      changes over 6 months.

PMID- 24287978
TI  - Nanoscale mechanics by tomographic contact resonance atomic force microscopy.
AB  - We report on quantifiable depth-dependent contact resonance AFM (CR-AFM)
      measurements over polystyrene-polypropylene (PS-PP) blends to detail surface and
      sub-surface features in terms of elastic modulus and mechanical dissipation. The
      depth-dependences of the measured parameters were analyzed to generate cross
      sectional images of tomographic reconstructions. Through a suitable normalization
      of the measured contact stiffness and indentation depth, the depth-dependence of
      the contact stiffness was analyzed by linear fits to obtain the elastic moduli of
      the materials probed. Besides elastic moduli, the contributions of adhesive
      forces (short-range versus long-range) to contact on each material were
      determined without a priori assumptions. The adhesion analysis was complemented
      by an unambiguous identification of distinct viscous responses during adhesion
      and in-contact deformation from the dissipated power during indentation. 

PMID- 24287977
TI  - Upregulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in
      mouse brain microvascular endothelial cells.
AB  - Endothelin-1 (ET-1), a proinflammatory mediator, is elevated in the regions of
      several brain inflammatory disorders, implying that ET-1 may contribute to
      inflammatory responses. The deleterious effects of ET-1 on brain endothelial
      cells may aggravate brain inflammation mediated through the upregulation of
      cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) system. However, the signaling
      mechanisms underlying ET-1-induced COX-2 expression in mouse brain microvascular
      endothelial cells (bEnd.3 cells) remain unclear. Herein, we investigated the
      effects of Ca2+-dependent protein kinases on ET-1-induced COX-2 expression and
      PGE2 release in bEnd.3 cells. The data obtained with Western blotting, reverse
      transcription PCR, and intracellular Ca2+ analyses showed that ET-1-induced COX-2
      expression was mediated through phosphatidylinositol-phospholipase C (PI-PLC) and
      phosphatidylcholine-phospholipase C (PC-PLC)/Ca2+-dependent activation of protein
      kinase C-alpha (PKC-alpha) and calmodulin kinase II (CaMKII) cascades. Next, we
      demonstrated that ET-1 stimulated intracellular Ca2+ increase, phoshorylation of
      PKC-alpha, CaMKII, and mitogen-activated protein kinases (MAPKs) (ERK1/2, p38
      MAPK, and JNK1/2) and then activated the activating transcription factor 2
      (ATF2)/activator protein 1 (AP-1) via Gq/i protein-coupled ETB receptors.
      Moreover, the data of chromatin immunoprecipitation and promoter reporter assay
      demonstrated that the activated ATF2/AP-1 and p300 bound to its corresponding
      binding sites within COX-2 promoter, thereby turning on COX-2 gene transcription.
      Finally, upregulation of COX-2 by ET-1 promoted PGE2 biosynthesis and release in
      these cells. Taken together, these results demonstrate that in bEnd.3 cells, Ca2+
      dependent PKC-alpha and CaMKII linking to MAPKs, ATF2/AP-1, and p300 cascade is
      essential for ET-1-induced COX-2 upregulation. Understanding the mechanisms of
      COX-2/PGE2 system upregulated by ET-1 on brain microvascular endothelial cells
      may provide rational therapeutic interventions for brain injury and inflammatory
      diseases.

PMID- 24287979
TI  - Are the long term results of a high-flex total knee replacement affected by the
      range of flexion?
AB  - PURPOSE: The purpose of this study was to examine the effect of deep flexion on
      the long-term durability of a high-flex ceramic implant in total knee
      arthroplasty. METHODS: Five hundred and five consecutive knees replaced with a Bi
      Surface knee system (Kyocera Medical, Osaka, Japan) were divided into two groups
      according to the range of flexion by 135 degrees  postoperatively. Comparison of
      implant durability was made between the high- and low-flexion groups after a
      minimum ten year follow-up. RESULTS: With revision for any surgery as the end
      point, the survival rates at ten years were 95.5% and 96.2% in the high- and low
      flexion group, respectively (p = 0.63). With revision for mechanical failure as
      the end point, survival rates were 98.7% and 98.5%, respectively (p = 0.94).
      CONCLUSION: Implant survival rate was similar for both groups. Deep flexion
      seemed not to affect long-term durability.

PMID- 24287980
TI  - Particulate cartilage under bioreactor-induced compression and shear.
AB  - PURPOSE: Our aim was to explore the effect of varying in vitro culture conditions
      on general chondrogenesis of minced cartilage (MC) fragments. METHODS: Minced,
      fibrin-associated, bovine articular cartilage fragments were cultured in vitro
      within polyurethane scaffold rings. Constructs were maintained either free
      swelling for two or four weeks (control), underwent direct mechanical knee-joint
      specific bioreactor-induced dynamic compression and shear, or they were
      maintained free swelling for two weeks followed by two weeks of bioreactor
      stimulation. Samples were collected for glycosaminoglycan (GAG)/DNA
      quantification; collagen type I, collagen type II, aggrecan, cartilage oligomeric
      matrix protein (COMP), proteoglycan-4 (PRG-4) messenger RNA (mRNA) analysis;
      histology and immunohistochemistry. RESULTS: Cellular outgrowth and neomatrix
      formation was successfully accomplished among all groups. GAG/DNA and collagen
      type I mRNA were not different between groups; chondrogenic genes collagen type
      II, aggrecan and COMP revealed a significant downregulation among free-swelling
      constructs over time (week two through week four). Mechanical loading was able to
      maintain chondrogenic expression with significantly stronger expression at long
      term time points (four weeks) in comparison with four-week control. Histology and
      immunohistochemistry revealed that bioreactor culture induced stronger cellular
      outgrowth than free-swelling constructs. However, weaker collagen type II and
      aggrecan expression with an increased collagen type I expression was noted among
      this outgrowth neotissue. CONCLUSIONS: The method of MC culture is feasible under
      in vitro free-swelling and dynamic loading conditions, simulating in vivo
      posttransplantation. Mechanical stimulation significantly provokes cellular
      outgrowth and long-term chondrogenic maturation at the mRNA level, whereas
      histology depicts immature neotissue where typical cartilage matrix is expected.

PMID- 24287981
TI  - Precipitation of hydroxyapatite on electrospun polycaprolactone/aloe vera/silk
      fibroin nanofibrous scaffolds for bone tissue engineering.
AB  - Advances in electrospun nanofibres with bioactive materials have enhanced the
      scope of fabricating biomimetic scaffolds for tissue engineering. The present
      research focuses on fabrication of polycaprolactone/aloe vera/silk fibroin
      nanofibrous scaffolds by electrospinning followed by hydroxyapatite deposition by
      calcium-phosphate dipping method for bone tissue engineering. Morphology,
      composition, hydrophilicity and mechanical properties of polycaprolactone/aloe
      vera/silk fibroin-hydroxyapatite nanofibrous scaffolds along with controls
      polycaprolactone and polycaprolactone/aloe vera/silk fibroin nanofibrous
      scaffolds were examined by field emission scanning electron microscopy, Fourier
      transform infrared spectroscopy, contact angle and tensile tests, respectively.
      Adipose-derived stem cells cultured on polycaprolactone/aloe vera/silk fibroin
      hydroxyapatite nanofibrous scaffolds displayed highest cell proliferation,
      increased osteogenic markers expression (alkaline phosphatase and osteocalcin),
      osteogenic differentiation and increased mineralization in comparison with
      polycaprolactone control. The obtained results indicate that
      polycaprolactone/aloe vera/silk fibroin-hydroxyapatite nanofibrous scaffolds have
      appropriate physico-chemical and biological properties to be used as biomimetic
      scaffolds for bone tissue regeneration.

PMID- 24287982
TI  - A novel combination of nano-scaffolds with micro-scaffolds to mimic
      extracellularmatrices improve osteogenesis.
AB  - To improve bone engineering for clinical applications, we coupled nanofiber
      peptide hydrogel to nano-hydroxyapatite/collagen to form a bioactive scaffold
      (cnHAC) that mimics extracellular matrices. In comparison to nano
      hydroxyapatite/collagen, we found that cnHAC promoted cell adhesion and
      spreading, and DNA content measurements, alkaline phosphatase activity assays,
      and reverse transcriptase-polymerase chain reaction analyses of osteogenic gene
      expression showed that cnHAC significantly improved cellular attachment,
      proliferation, and osteogenic differentiation in vitro (P < 0.05). In vivo models
      based on rat calvarial implants showed that cnHAC significantly enhanced bone
      regeneration (P < 0.05). In conclusion, we demonstrated that novel cnHAC
      scaffolds could potentially facilitate future bone regenerative medicine.

PMID- 24287983
TI  - Specific ultraviolet-C irradiation energy for functionalization of titanium
      surface to increase osteoblastic cellular attachment.
AB  - PURPOSE: The objective of this in vitro study was to examine the influence of the
      total energy of ultraviolet-C preirradiation on the number and morphology of
      osteoblastic cells attached to turned or acid-etched titanium surfaces, and
      physicochemical properties of the surface. MATERIALS AND METHODS: Rat bone marrow
      derived osteoblasts were incubated with turned or acid-etched titanium disks
      preirradiated with ultraviolet-C at 1 or 3 mW/cm(2), resulting in total energies
      of 10, 100, 250, 400, 500, 600, 750, or 1000 J/cm(2). Osteoblast attachment to
      the surface was evaluated using the WST-1 assay. Physicochemical changes of the
      titanium were evaluated by measuring water wettability and X-ray photoelectron
      spectroscopy analysis. RESULTS: Number of attached cells was greater on turned or
      acid-etched surface preirradiated with 500 or 750 J/cm(2) of 3 mW/cm(2)
      ultraviolet-C than on the nonirradiated surface, respectively. However, the
      further irradiation energy did not increase the numbers on both types of the
      surfaces. These phenomena were also seen on the surfaces preirradiated at
      different ultraviolet-C intensities. Ultraviolet-C irradiation induced
      superhydrophilicity on both types of surface even with the less irradiation
      energy. The amount of carbon on ultraviolet-C preirradiated titanium surfaces
      decreased gradually with an increase in the total irradiation energy. CONCLUSION:
      Specific ultraviolet-C energy used to irradiate turned or acid-etched surfaces
      increased the number of osteoblastic cells attached to each of the surface. This
      was canceled by overirradiation, despite maintenance of both the acquired
      superhydrophilicity and the accompanying reduction in carbon on each surface.

PMID- 24287984
TI  - General approach for introduction of various chemical labels in specific RNA
      locations based on insertion of amino linkers.
AB  - Introduction of reporter groups at designed RNA sites is a widely accepted
      approach to gain information about the molecular environment of RNAs in their
      complexes with other biopolymers formed during various cellular processes. A
      general approach to obtain RNAs bearing diverse reporter groups at designed
      locations is based on site-specific insertion of groups containing primary
      aliphatic amine functions (amino linkers) with their subsequent selective
      derivatization by appropriate chemicals. This article is a brief review on
      methods for site-specific introduction of amino linkers in different RNAs. These
      methods comprise: (i) incorporation of a nucleoside carrying an amino-linker or a
      function that can be substituted with it into oligoribonucleotides in the course
      of their chemical synthesis; (ii) assembly of amino linker-containing RNAs from
      short synthetic fragments via their ligation; (iii) synthesis of amino linker
      modified RNAs using T7 RNA polymerase; (iv) insertion of amino linkers into
      unmodified RNAs at functional groups of a certain type such as the 5'-phosphates
      and N7 of guanosine residues and (v) introduction of an amino linker into long
      highly structured RNAs exploiting an approach based on sequence-specific
      modification of nucleic acids. Particular reporter groups used for derivatization
      of amino linker-containing RNAs together with types of RNA derivatives obtained
      and fields of their application are presented. 

PMID- 24287986
TI  - Three new ursane-type triterpenoids from the stems of Saprosma merrillii.
AB  - Three new ursane-type triterpenoids, 3alpha,6alpha,30-trihydroxy-ursan-28-oic
      acid (1), 3alpha,30-dihydroxy-6-oxo-ursan-28-oic acid (2) and
      3alpha,6alpha,7alpha,30-tetrahydroxy-ursan-28-oic acid (3), together with one
      known triterpenoid, betulinic acid (4), one known anthraquinone, 1,7-dihydroxy-2
      methylanthraquinone (5), four known phenols, 1,3,5-trimethoxybenzene (6), p
      hydroxybenzoic acid (7), syringic acid (8), isovanillin (9), two steroids,
      sitosterol (10) and daucosterol (11), were isolated from the ethanol extract of
      the stems of S. merrillii. Their structures were elucidated on the basis of
      physical and spectral techniques, besides comparison with literature data.
      Compounds 1-3 showed inhibitory activities against the A549, HEPG2, and B16F10
      cell lines. 

PMID- 24287987
TI  - Facile creation of 3-substituted-3-hydroxy-2-oxindoles by arginine-catalyzed
      aldol reactions of alpha,beta-unsaturated ketones with isatins.
AB  - An efficient approach for the synthesis of 3-substituted-3-hydroxy-2-oxindoles
      has been achieved via an aldol reaction of alpha,beta-unsaturated ketones and
      isatins using arginine as an organocatalyst. A range of 3-substituted-3-hydroxy-2
      oxindoles were obtained in moderate to high (up to 99%) yields. These 3
      substituted-3-hydroxy-2-oxindoles with an additional enone moiety provide an
      opportunity for further elaboration of the products and for potentially
      interesting biological activities. In addition, the formation of 3-substituted-3
      hydroxy-2-oxindole 3a was confirmed by X-ray crystallography. The possible
      reaction mechanism reveals that the reaction proceeds via a double action
      process. 

PMID- 24287985
TI  - Cytochrome P450 family 1 inhibitors and structure-activity relationships.
AB  - With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s,
      thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and
      1B1) have been identified and studied. Generally, planar polycyclic molecules
      such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are
      considered to potentially be effective inhibitors of these enzymes, however, the
      details of the structure-activity relationships and selectivity of these
      inhibitors are still ambiguous. In this review, we thoroughly discuss the
      selectivity of many representative P450 family 1 inhibitors reported in the past
      20 years through a meta-analysis. 

PMID- 24287988
TI  - Ultrasound-promoted one-pot, four-component synthesis of pyridin-2(1H)-one
      derivatives.
AB  - An efficient one-pot synthesis of 1,6-diamino-2-oxo-1,2,3,4-tetrahydro- pyridine
      3,5-dicarbonitrile derivatives by four-component piperidine-catalyzed reactions
      of a ketone, malononitrile, ethyl cyanoacetate and hydrazine hydrate under
      ultrasound irradiation is described. This method provides several advantages such
      as shorter reaction times, excellent yields, and a simple workup procedure. 

PMID- 24287989
TI  - Perfluoroalkanesulfonamide organocatalysts for asymmetric conjugate additions of
      branched aldehydes to vinyl sulfones.
AB  - Asymmetric conjugate additions of branched aldehydes to vinyl sulfones promoted
      by sulfonamide organocatalyst 6 or 7 have been developed, allowing facile
      synthesis of the corresponding adducts with all-carbon quaternary stereocenters
      in excellent yields with up to 95% ee. 

PMID- 24287990
TI  - Evaluation of sulfated polysaccharides from the brown seaweed Dictyopteris justii
      as antioxidant agents and as inhibitors of the formation of calcium oxalate
      crystals.
AB  - Oxalate crystals and other types of crystals are the cause of urolithiasis, and
      these are related to oxidative stress. The search for new compounds with
      antioxidant qualities and inhibitors of these crystal formations is therefore
      necessary. In this study, we extracted four sulfated polysaccharides, a
      fucoglucoxyloglucuronan (DJ-0.3v), a heterofucan (DJ-0.4v), and two glucans (DJ
      0.5v and DJ-1.2v), from the marine alga Dictyopteris justii. The presence of
      sulfated polysaccharides was confirmed by chemical analysis and FT-IR. All the
      sulfated polysaccharides presented antioxidant activity under different
      conditions in some of the in vitro tests and inhibited the formation of calcium
      oxalate crystals. Fucan DJ-0.4v was the polysaccharide that showed the best
      antioxidant activity and was one of the best inhibitors of the crystallization of
      calcium oxalate. Glucan DJ-0.5v was the second most potent inhibitor of the
      formation of oxalate crystals, as it stabilized dehydrated oxalate crystals (less
      aggressive form), preventing them from transforming into monohydrate crystals
      (more aggressive form). The obtained data lead us to propose that these sulfated
      polysaccharides are promising agents for use in the treatment of urolithiasis. 

PMID- 24287991
TI  - Insights into structure-activity relationships of somatostatin analogs containing
      mesitylalanine.
AB  - The non-natural amino acid mesitylalanine (2,4,6-trimethyl-L-phenylalanine; Msa)
      has an electron-richer and a more conformationally restricted side-chain than
      that of its natural phenylalanine counterpart. Taking these properties into
      account, we have synthesized ten somatostatin analogs containing Msa residues in
      different key positions to modify the intrinsic conformational flexibility of the
      natural hormone. We have measured the binding affinity of these analogs and
      correlated it with the main conformations they populate in solution. NMR and
      computational analysis revealed that analogs containing one Msa residue were
      conformationally more restricted than somatostatin under similar experimental
      conditions. Furthermore, we were able to characterize the presence of a hairpin
      at the pharmacophore region and a non-covalent interaction between aromatic
      residues 6 and 11. In all cases, the inclusion of a D-Trp in the eighth position
      further stabilized the main conformation. Some of these peptides bound
      selectively to one or two somatostatin receptors with similar or even higher
      affinity than the natural hormone. However, we also found that multiple
      incorporations of Msa residues increased the life span of the peptides in serum
      but with a loss of conformational rigidity and binding affinity. 

PMID- 24287992
TI  - Astataricusones A-D and astataricusol A, five new anti-HBV shionane-type
      triterpenes from Aster tataricus L. f.
AB  - Five new shionane-type triterpenes, astataricusones A-D (compounds 1-4) and
      astataricusol A (5), together with one known shionane-type triterpene 6 were
      obtained from the roots and rhizomes of Aster tataricus L. f. Their structures
      were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The
      absolute configurations of 1 and 4 was determined by single crystal X-ray
      diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg
      secretion with an IC50 value of 23.5 MUM, while 2 and 6 showed inhibitory
      activities on HBeAg secretion with IC50 values of 18.6 and 40.5 MUM, and
      cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 MUM,
      respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA
      replication with IC50 values of 2.7 and 30.7 MUM, respectively. 

PMID- 24287993
TI  - Nutraceutical value of black cherry Prunus serotina Ehrh. fruits: antioxidant and
      antihypertensive properties.
AB  - In Mexico black cherry (Prunus serotina Ehrh.) fruits are consumed fresh, dried
      or prepared in jam. Considering the evidence that has linked intake of fruits and
      vegetables rich in polyphenols to cardiovascular risk reduction, the aim of this
      study was to characterize the phenolic profile of black cherry fruits and to
      determine their antioxidant, vasorelaxant and antihypertensive effects. The
      proximate composition and mineral contents of these fruits were also assessed.
      Black cherry fruits possess a high content of phenolic compounds and display a
      significant antioxidant capacity. High-performance liquid chromatography/mass
      spectrometric analysis indicated that hyperoside, anthocyanins and chlorogenic
      acid were the main phenolic compounds found in these fruits. The black cherry
      aqueous extract elicited a concentration-dependent relaxation of aortic rings and
      induced a significant reduction on systolic blood pressure in L-NAME induced
      hypertensive rats after four weeks of treatment. Proximate analysis showed that
      black cherry fruits have high sugar, protein, and potassium contents. The results
      derived from this study indicate that black cherry fruits contain phenolic
      compounds which elicit significant antioxidant and antihypertensive effects.
      These findings suggest that these fruits might be considered as functional foods
      useful for the prevention and treatment of cardiovascular diseases. 

PMID- 24287994
TI  - Liposomal encapsulation enhances in vivo near infrared imaging of exposed
      phosphatidylserine in a mouse glioma model.
AB  - We have previously demonstrated that exposed phosphatidylserine (PS) on tumor
      vascular endothelial cells is highly tumor specific, and development of the PS
      targeted near infrared (NIR) optical probe enables successful in vivo optical
      imaging of U87 gliomas in a mouse model. Liposomes have been widely used as a
      nanovector for delivery of chemotherapeutics and imaging contrast agents due to
      their high payload and longer circulation time. In the current study, we have
      fabricated PS-targeted liposomal nanoprobes encapsulating a NIR dye, IRDye(r)
      800CW, aiming to enhance PS-targeted tumor imaging. Hydrophilic 800CW dye was
      packed into the core of polyethylene glycol (PEG)-coated liposomes functionalized
      with F(ab')2 fragments of PGN635, a fully human monoclonal antibody that binds
      PS. As expected, in vivo dynamic NIR imaging revealed significantly improved
      tumor/normal contrast (TNR = 20 +/- 3; p < 0.01) of subcutaneous U87 gliomas in
      mice after injection of the liposomal nanoprobes. Markedly enhanced TNR was
      observed after the tumors were irradiated to increase PS exposure (TNR = 48 +/-
      6; p < 0.05). Intriguingly, the liposomal nanoprobes, PGN-L-800CW showed distinct
      biodistribution and pharmacokinetics compared to the 800CW-PGN probes used in our
      previous study. Our data further suggest the usefulness of PS-targeted imaging
      probes for sensitive tumor detection and the potential of utilizing liposomal
      platform for glioma theranostics. 

PMID- 24287995
TI  - Bio-activity and dereplication-based discovery of ophiobolins and other fungal
      secondary metabolites targeting leukemia cells.
AB  - The purpose of this study was to identify and characterize fungal natural
      products (NPs) with in vitro bioactivity towards leukemia cells. We based our
      screening on a combined analytical and bio-guided approach of LC-DAD-HRMS
      dereplication, explorative solid-phase extraction (E-SPE), and a co-culture
      platform of CLL and stromal cells. A total of 289 fungal extracts were screened
      and we tracked the activity to single compounds in seven of the most active
      extracts. The novel ophiobolin U was isolated together with the known ophiobolins
      C, H, K as well as 6-epiophiobolins G, K and N from three fungal strains in the
      Aspergillus section Usti. Ophiobolins A, B, C and K displayed bioactivity towards
      leukemia cells with induction of apoptosis at nanomolar concentrations. The
      remaining ophiobolins were mainly inactive or only slightly active at micromolar
      concentrations. Dereplication of those ophiobolin derivatives possessing
      different activity in combination with structural analysis allowed a correlation
      of the chemical structure and conformation with the extent of bioactivity,
      identifying the hydroxy group at C3 and an aldehyde at C21, as well as the A/B
      cis ring structure, as indispensible for the strong activity of the ophiobolins.
      The known compounds penicillic acid, viridicatumtoxin, calbistrin A, brefeldin A,
      emestrin A, and neosolaniol monoacetate were identified from the extracts and
      also found generally cytotoxic. 

PMID- 24287996
TI  - Anti- and pro-lipase activity of selected medicinal, herbal and aquatic plants,
      and structure elucidation of an anti-lipase compound.
AB  - Plants that help in slowing down the digestion of triacylglycerols (TAGs) in the
      pancreas and small intestine of humans play an important role in the reduction of
      obesity. On the other hand, there may be plants or plant parts that stimulate
      intestinal lipolytic activity, thus contributing to greater TAG assimilation. The
      aim of this study was to evaluate the aqueous methanolic extracts of ninety eight
      (98) medicinal, herbal and aquatic plant materials from Malaysia for their effect
      on porcine pancreatic lipase (PPL) activity and to identify the structure of an
      anti-lipase compound from one of the sources. The degree of inhibition was also
      quantified as relative to orlistat activity against PPL (orlistat equivalents).
      Results revealed that while 19.4% of the extracts were found to have anti-lipase
      activity >=80%, 12% were actually found to promote PPL activity. Twenty two
      percent (22.4%) exhibited moderate inhibition (41%-80%) and 2% were neutral
      toward PPL activity. The ripe fruit of Averrhoa carambola and the leaves of
      Archidendron jiringa (Jack) I.C Nielsen L. (jering), Cynometra cauliflora (nam
      nam) and Aleurites moluccana (L.) Willd (candle nut/buah keras) had the highest
      (100%) anti-lipase activity and are equivalent to 0.11 ug orlistat/mL. Plants
      that stimulated lipase activity included Pimpinella anisum L. (aniseed/jintan
      manis), activating the enzyme by 186.5%. Kaempferol 3-O-rhamnoside was isolated
      from the ethyl acetate fraction of C. cauliflora leaves and found to be an active
      lipase inhibitor. The structure was elucidated using 1H-NMR, 13C-NMR and 2D-NMR
      analyses. 

PMID- 24287997
TI  - Traditional Korean East Asian medicines and herbal formulations for cognitive
      impairment.
AB  - Hanbang, the Traditional Korean Medicine (TKM), is an inseparable component of
      Korean culture both within the country, and further afield. Korean traditional
      herbs have been used medicinally to treat sickness and injury for thousands of
      years. Oriental medicine reflects our ancestor's wisdom and experience, and as
      the elderly population in Korea is rapidly increasing, so is the importance of
      their health problems. The proportion of the population who are over 65 years of
      age is expected to increase to 24.3% by 2031. Cognitive impairment is common with
      increasing age, and efforts are made to retain and restore the cognition ability
      of the elderly. Herbal materials have been considered for this purpose because of
      their low adverse effects and their cognitive-enhancing or anti-dementia
      activities. Herbal materials are reported to contain several active compounds
      that have effects on cognitive function. Here, we enumerate evidence linking TKMs
      which have shown benefits in memory improvements. Moreover, we have also listed
      Korean herbal formulations which have been the subject of scientific reports
      relating to memory improvement. 

PMID- 24287998
TI  - Two-year variations of phenolics, flavonoids and antioxidant contents in acacia
      honey.
AB  - Honey is a good source of several important chemical compounds and antioxidants
      and is harvested throughout the year. However, no study has determined how their
      contents change over the years. The aim of the present research was to
      investigate the changes in the phenolics, flavonoids and antioxidant properties,
      as well as other physicochemical properties, of Malaysian acacia honey collected
      during different months during a two year period. The DPPH (1,1-diphenyl-2
      picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods were used to
      determine the total antioxidant activity of the honey samples. Generally, honey
      samples collected in the beginning and the middle of the year tended to have
      higher sugar content, which may be attributed to its high acidic nature and low
      moisture content. There was a gradual increase in the phenolic content of the
      acacia honey samples collected between September 2010 and December 2010. The
      honey sample collected at the beginning of the year (January) showed the highest
      color intensity and was dark amber in color. It also contained the highest
      concentration of phenolic compounds (341.67 +/- 2.94 mg(gallic acid)/kg), the
      highest flavonoid content (113.06 +/- 6.18 mg(catechin)/kg) and the highest
      percentage of DPPH inhibition and the highest FRAP value, confirming its high
      antioxidant potential. There was a positive correlation between DPPH and total
      phenolic content, suggesting that phenolic compounds are the strongest
      contributing factor to the radical scavenging activity of Malaysian acacia
      honeys. Overall, our results indicated that there were significant seasonal
      variations in the antioxidant potentials of honey over the two year period and
      the time of honey collection affects its physicochemical properties. Therefore,
      acacia honey from Malaysia should ideally be collected during the dry season,
      particularly in the months of January, May and June.

PMID- 24287999
TI  - Design and synthesis of arylthiophene-2-carbaldehydes via Suzuki-Miyaura
      reactions and their biological evaluation.
AB  - A series of various novel 4-arylthiophene-2-carbaldehyde compounds were
      synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling
      with different arylboronic pinacol esters/acids. The synthesized products were
      screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO)
      scavenging capabilities and interestingly, almost all products turned out to have
      good activities. 3-(5-Formyl-thiophene-3-yl)-5-(trifloromethyl)benzonitrile (2d)
      revealed excellent antibacterial activity, showing an IC50 value of 29.7 ug/mL
      against Pseudomonas aeruginosa, compared to the standard drug streptomycin with
      an IC50 value 35.2 ug/mL and was also found to be the best NO scavenger, with an
      IC50 value of 45.6 ug/mL. Moreover, 4-(3-chloro-4-fluoro-phenyl)thiophene-2
      carbaldehyde (2i) exhibited a superior haemolytic action and an outstanding
      urease inhibition, showing an IC50 value of 27.1 ug/mL. 

PMID- 24288000
TI  - Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y
      cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein
      expression.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      progressive loss of dopaminergic (DA) neurons at the substantia nigra.
      Mitochondrial dysfunction is involved in the mechanism of cell damage in
      Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a dopamine analog which
      specifically damages dopaminergic neurons. Baicalein has been previously reported
      to have potential in the treatment of PD. The purpose of the present study was to
      investigate the mechanism of action of baicalein against 6-OHDA injury in SH-SY5Y
      cells. The results showed that baicalein significantly alleviated alterations of
      mitochondrial redox activity and mitochondrial membrane potential induced by 6
      OHDA in a dose-dependent manner in SH-SY5Y cells compared with vehicle group.
      Futhermore, baicalein decreased the production of ROS and upregulated the DJ-1
      protein expression in SH-SY5Y cells. In addition, baicalein also inhibited ROS
      production and lipid peroxidation (IC50 = 6.32 +/- 0.03 MUM) in rat brain
      mitochondia. In summary, the underlying mechanisms of baicalein against 6-OHDA
      induced mitochondrial dysfunction may involve inhibition of mitochondrial
      oxidation and upregulation of DJ-1 protein expression. 

PMID- 24288001
TI  - Examination of the potential for adaptive chirality of the nitrogen chiral center
      in aza-aspartame.
AB  - The potential for dynamic chirality of an azapeptide nitrogen was examined by
      substitution of nitrogen for the alpha-carbon of the aspartate residue in the
      sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet
      and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be
      indicative of a low isomerization barrier for nitrogen chirality inter
      conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and
      peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the
      solid state; however, the aza-residue chiral center was considerably flattened
      relative to its natural amino acid counterpart. On tasting, the authors
      considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter
      sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in
      the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of
      which may interfere with recognition by taste receptors. 

PMID- 24288002
TI  - OxymaPure/DIC: an efficient reagent for the synthesis of a novel series of 4-[2
      (2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives.
AB  - OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for
      use in the carbodiimide (DIC) approach for the synthesis of a novel series of
      alpha-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl
      amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or
      carbodiimide alone in terms of purity and yield. The title compounds were
      synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was
      reacted with 4-aminobenzoic acid under conventional heating as well as microwave
      irradiation to afford 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid. This
      alpha-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as
      a coupling reagent to afford 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl
      amino acid ester derivatives in excellent yield and purity. The synthesized
      compounds were characterized using FT-IR, NMR, and elemental analysis. 

PMID- 24288003
TI  - G-quadruplexes as sensing probes.
AB  - Guanine-rich sequences of DNA are able to create tetrastranded structures known
      as G-quadruplexes; they are formed by the stacking of planar G-quartets composed
      of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as
      ligands for metal ions and aptamers for various molecules. Interestingly, the G
      quadruplexes form a complex with anionic porphyrin hemin and exhibit peroxidase
      like activity. This review focuses on overview of sensing techniques based on G
      quadruplex complexes with anionic porphyrins for detection of various analytes,
      including metal ions such as K+, Ca2+, Ag+, Hg2+, Cu2+, Pb2+, Sr2+, organic
      molecules, nucleic acids, and proteins. Principles of G-quadruplex-based
      detection methods involve DNA conformational change caused by the presence of
      analyte which leads to a decrease or an increase in peroxidase activity,
      fluorescence, or electrochemical signal of the used probe. The advantages of
      various detection techniques are also discussed. 

PMID- 24288004
TI  - Primary surgery vs primary sclerotherapy for head and neck lymphatic
      malformations.
AB  - IMPORTANCE: The optimal treatment for head and neck lymphatic malformations (LMs)
      is unknown. To our knowledge, this is the first head-to-head comparison of
      primary surgery and sclerotherapy for this condition. OBJECTIVE: To compare
      surgery and sclerotherapy as initial treatment for head and neck LMs. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective cohort study including patients in 2
      pediatric vascular anomaly programs receiving treatment for head and neck LMs.
      INTERVENTIONS: Primary surgery or primary sclerotherapy and any subsequent
      therapy within 1 year. MAIN OUTCOMES AND MEASURES: Treatment effectiveness was
      measured by (1) need for further therapy after first treatment and within 1 year
      and (2) change in Cologne Disease Score (CDS). Resource utilization was reflected
      by total intervention number, hospital and intensive care unit (ICU) days, and
      tracheostomy placement. RESULTS: A total of 174 patients were studied. Their mean
      (SD) age at presentation was 4.2 (4.7) years; 45.1% were female. The initial
      treatment was surgery in 55.8%, sclerotherapy in 35.1%, and other interventions
      in 9.1%. The LM stage ranged from 1 to 5, with similar distributions (P = .15)
      across initial treatment types; 31.2% of LMs were macrocystic, 34.8% were
      microcystic, and 33.9% were mixed, with similar distributions across treatment
      types. Patients receiving sclerotherapy had worse pretreatment CDS subscores for
      respiration, nutrition, and speech (all P <= .02). In univariate analysis,
      initial surgery and initial sclerotherapy had similar effectiveness after the
      first intervention (P = .21) and at 1 year (P = .30). In multivariate analysis
      controlling for lesion stage and type, initial surgery and sclerotherapy did not
      differ in effectiveness after the first intervention (P = .28) or at 1 year (P =
      .97). Total CDS and subscale changes were similar between treatment types except
      for the nutrition subscale. Treatment type did not predict total number of
      interventions (P = .64), total hospital days (P = .34), total ICU days (P = .59),
      or higher likelihood of subsequent tracheostomy (P = .36). Higher LM stage
      predicted more hospital and ICU days and higher likelihood of tracheostomy (all P
      <= .02). CONCLUSIONS AND RELEVANCE: In this multisite comparison, initial surgery
      and sclerotherapy for head and neck LMs were similar in effectiveness and
      resource utilization. Higher stage predicted greater resource utilization.

PMID- 24288005
TI  - Mobility enhancement of SnO2 nanowire transistors gated with a nanogranular SiO2
      solid electrolyte.
AB  - Field-effect transistors (FETs) based on semiconducting nanowires are the most
      fundamental electronic elements for exploring charge transport as well as
      possible applications in functional nanoelectronics. Here, we report the effect
      of different gate dielectrics on the electrical performance of SnO2 nanowire
      FETs. By using solid-electrolytes with large electric-double-layer (EDL)
      capacitance as gate dielectrics, both low-voltage operation and high gating
      efficiency can be obtained. Electrical transport measurements indicate that the
      nanowire FETs gated by solid-electrolytes show improved electrical performances
      in terms of on-current, sub-threshold swing, and mobility, in comparison to those
      gated by traditional thermally grown dielectrics. The observed performance
      improvement is possibly due to the reduction of the contact-resistance and the
      Schottky barrier at the semiconductor/metal junctions. 

PMID- 24288006
TI  - Sleep duration and body mass index in children and adolescents with and without
      obstructive sleep apnea.
AB  - PURPOSE: The prevalence of pediatric obesity and short sleep duration has
      simultaneously increased in recent decades. Sleep plays a critical role in
      metabolic and endocrine regulation and insufficient sleep has been shown to be
      associated with changes in metabolism. Obesity, a major risk factor for
      obstructive sleep apnea (OSA), has been also associated with metabolic
      dysregulation. Despite this, no study investigating short sleep and obesity has
      addressed the potential confounder of OSA. The aim of this study was to
      investigate the association between short sleep duration and obesity in children
      with and without OSA. METHODS: In this retrospective study, 306 children who
      underwent polysomnography between January and December 2010 were included. A
      diagnosis of OSA was made if the apnea/hypopnea index on polysomnography is >=1.
      Typical sleep times were obtained by parental report. Short sleep duration was
      defined as a reduction of >1 h from the minimum total sleep time (TST)
      recommended for age from the National Sleep Foundation (NSF). RESULTS: Overall,
      32% were obese, 39.5% had short sleep duration, and 78% had OSA. Children with
      OSA had a similar frequency of short sleep duration than those without (39.6 vs.
      42.4%, p = 0.950). In children with short sleep duration, the odds ratio for
      obesity was 2.5 (95% CI 1.3-4.9; p = 0.009) compared to children with TST within
      normal limits even after accounting for the presence of OSA. CONCLUSION: A
      parental history of total sleep duration of only 1 h less than recommended per
      age by the NSF is associated with a higher risk for obesity in children
      independently of the presence of OSA.

PMID- 24288007
TI  - Flt3L dependence helps define an uncharacterized subset of murine cutaneous
      dendritic cells.
AB  - Skin-derived dendritic cells (DCs) are potent antigen-presenting cells with
      critical roles in both adaptive immunity and tolerance to self. Skin DCs carry
      antigens and constitutively migrate to the skin-draining lymph nodes (LNs). In
      mice, Langerin-CD11b- dermal DCs are a low-frequency, heterogeneous, migratory DC
      subset that traffics to LNs (Langerin-CD11b- migDCs). Here, we build on the
      observation that Langerin-CD11b- migDCs are Fms-like tyrosine kinase 3 ligand
      (Flt3L) dependent and strongly Flt3L responsive, which may relate them to
      classical DCs. Examination of DC capture of FITC from painted skin, DC isolation
      from skin explant culture, and from the skin of CCR7 knockout mice, which
      accumulate migDCs, demonstrate these cells are cutaneous residents. Langerin
      CD11b- Flt3L-responsive DCs are largely CD24(+) and CX3CR1(low) and can be
      depleted from Zbtb46-DTR mice, suggesting classical DC lineage. Langerin-CD11b-
      migDCs present antigen with equal efficiency to other DC subsets ex vivo,
      including classical CD8alpha cDCs and Langerin+CD103+ dermal DCs. Finally,
      transcriptome analysis suggests a close relationship with other skin DCs, and a
      lineage relationship with other classical DCs. This work demonstrates that
      Langerin- CD11b- dermal DCs, a previously overlooked cell subset, may be an
      important contributor to the cutaneous immune environment. 

PMID- 24288008
TI  - A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic
      neoplasms.
AB  - The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant
      proportion of melanomas, and PI3K pathway activation in combination with
      constitutively active mitogen-activated protein kinase signaling shows
      synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor
      suppressor function for the lipid phosphatase inositol polyphosphate 4
      phosphatase type II (INPP4B) has been described in breast and prostate cancers,
      with impact on PI3K signaling output. Given the importance of PI3K pathway
      activity for melanoma formation and growth, we aimed to assess the role of INPP4B
      in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B
      expression is an event correlating with tumor progression in melanocytic
      neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and
      exerts a tumor suppressor effect, impacting the proliferative, invasive, and
      tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic
      neoplasms may therefore have potential as a biomarker for disease progression and
      as a modulator for the prediction of treatment outcome. 

PMID- 24288009
TI  - Heterologous expression of Arabidopsis ABF4 gene in potato enhances tuberization
      through ABA-GA crosstalk regulation.
AB  - Potato (Solanum tuberosum L.) tuberization is regulated by many signals, such as
      abscisic acid (ABA), sucrose and gibberellic acid (GA). ABA and sucrose are
      positive modulators, while GA is an inhibitor of the process. ABF (ABRE-binding
      factor) proteins are transcription factors involved in ABA and stress signaling.
      Previously, we reported that S. tuberosum StABF1 could mediate the ABA effects on
      tuberization. The aim of the present study was to evaluate the potential use of
      ABF genes to enhance tuberization and to determine the molecular mechanism
      involved. For this purpose, transgenic potato plants expressing the Arabidopsis
      ABF4 or ABF2 genes were generated, and their tuberization capacity and response
      to tuberization-related signals were analyzed in vitro. The results indicate that
      both ABF4 and ABF2 proteins positively regulate potato tuber induction; however,
      only ABF4 expression significantly increases the number and weight of the tubers
      obtained, without stunting growth. ABF4 and ABF2 transgenic plants exhibit ABA
      hypersensitivity during tuberization, accompanied by a GA-deficient phenotype.
      ABF4 expression triggers a significant rise in ABA levels in stolons under tuber
      inducing conditions as compared with wild-type plants and a transcriptional
      deregulation of GA metabolism genes. Our results demonstrate that Arabidopsis
      ABF4 functions in potato ABA-GA signaling crosstalk during tuberization by
      regulating the expression of ABA- and GA-metabolism genes. ABF4 gene might be a
      potential tool to increase tuber production, since its heterologous expression in
      potato enhances tuber induction without affecting plant growth. 

PMID- 24288010
TI  - Is a policy of watch and wait after a complete response following neoadjuvant
      treatment for locally advanced rectal adenocarcinoma justified? Should we reset
      the limit?

PMID- 24288011
TI  - Management of rectosigmoid obstruction due to severe bowel endometriosis.
AB  - Bowel obstruction is a rare complication of intestinal endometriosis. The aim of
      this work was to evaluate outcomes after colorectal resection for bowel
      obstruction due to endometriosis. Of 720 patients who underwent colorectal
      resection for bowel endometriosis, 12 (1.7 %) presented with bowel obstruction.
      Preoperative work-up, management, perioperative and long-term outcomes were
      analyzed. All lesions were localized in the rectosigmoid tract. All patients
      underwent colorectal resection, which was carried out laparoscopically in 4 (33
      %). Rate of low or ultra-low colorectal anastomoses was 83 %. Four patients (33
      %) required blood transfusions. Two patients developed rectovaginal fistulas.
      After a median follow-up of 38 months, there were no cases of disease recurrence
      and dyschezia improved in 75 % of patients. Bowel endometriosis should be
      considered in the differential diagnosis of young women with bowel obstruction.
      Despite challenging operations, colorectal resections are associated with good
      outcomes.

PMID- 24288012
TI  - Quality indicators for the primary care of osteoarthritis: a systematic review.
AB  - OBJECTIVE: To identify valid and feasible quality indicators for the primary care
      of osteoarthritis (OA). DESIGN: Systematic review and narrative synthesis. DATA
      SOURCES: Electronic reference databases (MEDLINE, EMBASE, CINAHL, HMIC,
      PsychINFO), quality indicator repositories, subject experts. ELIGIBILITY
      CRITERIA: Eligible articles referred to adults with OA, focused on development or
      implementation of quality indicators, and relevant to UK primary care. An English
      language restriction was used. The date range for the search was January 2000 to
      August 2013. The majority of OA management guidance has been published within
      this time frame. DATA EXTRACTION: Relevant studies were quality assessed using
      previous quality indicator methodology. Two reviewers independently extracted
      data. Articles were assessed through the Outcome Measures in Rheumatology filter;
      indicators were mapped to management guidance for OA in adults. A narrative
      synthesis was used to combine the indicators within themes. RESULTS: 10,853
      articles were identified from the search; 32 were included in the review. Fifteen
      indicators were considered valid and feasible for implementation in primary care;
      these related to assessment non-pharmacological and pharmacological management.
      Another 10 indicators were considered less feasible, in various aspects of
      assessment and management. A small number of recommendations had no published
      corresponding quality indicator, such as use of topical non-steroidal anti
      inflammatory drugs. No negative ('do not do') indicators were identified.
      CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There are well-developed, feasible
      indicators of quality of care for OA which could be implemented in primary care.
      Their use would assist the audit and quality improvement for this common and
      frequently disabling condition.

PMID- 24288013
TI  - Methotrexate polyglutamates in erythrocytes are associated with lower disease
      activity in juvenile idiopathic arthritis patients.
AB  - OBJECTIVE: To determine association of erythrocyte methotrexate polyglutamates
      (MTX-PG) with disease activity and adverse effects in a prospective juvenile
      idiopathic arthritis (JIA) cohort. METHODS: One hundred and thirteen JIA patients
      were followed from MTX start until 12 months. Erythrocyte MTX-PGs with 1-5
      glutamate residues were measured at 3 months with tandem mass spectrometry. The
      outcomes were Juvenile Arthritis Disease Activity Score (JADAS)-27 and adverse
      effects. To determine associations of MTX-PGs with JADAS-27 at 3 months and
      during 1 year of MTX treatment, linear regression and linear mixed-model analyses
      were used. To determine associations of MTX-PGs with adverse effects during 1
      year of MTX treatment, logistic regression was used. Analyses were corrected for
      JADAS-27 at baseline and co-medication. RESULTS: Median JADAS-27 decreased from
      12.7 (IQR: 7.8-18.2) at baseline to 2.9 (IQR: 0.1-6.5) at 12 months. Higher
      concentrations of MTX-PG3 (beta: -0.006, p=0.005), MTX-PG4 (beta: -0.015,
      p=0.004), MTX-PG5 (beta: -0.051, p=0.011) and MTX-PG3-5 (beta: -0.004, p=0.003)
      were associated with lower disease activity at 3 months. Higher concentrations of
      MTX-PG3 (beta: -0.005, p=0.028), MTX-PG4 (beta: -0.014, p=0.014), MTX-PG5 (beta: 
      0.049, p=0.023) and MTX-PG3-5 (beta: -0.004, p=0.018) were associated with lower
      disease activity over 1 year. None of the MTX-PGs was associated with adverse
      effects. CONCLUSIONS: In the first prospective study in JIA, long-chain MTX-PGs
      were associated with lower JADAS-27 at 3 months and during 1 year of MTX
      treatment. Erythrocyte MTX-PG could be a plausible candidate for therapeutic drug
      monitoring of MTX in JIA.

PMID- 24288014
TI  - Discontinuation of adalimumab after achieving remission in patients with
      established rheumatoid arthritis: 1-year outcome of the HONOR study.
AB  - OBJECTIVES: To investigate the possibility of discontinuing adalimumab (ADA) for
      1 year without flaring (DAS28-erythrocyte sedimentation rate (ESR) >=3.2), and to
      identify factors enabling established patients with rheumatoid arthritis (RA) to
      remain ADA-free. METHODS: Of 197 RA patients treated with ADA+methotrexate (MTX),
      75 patients who met the ADA-free criteria (steroid-free and sustained DAS28-ESR
      remission for 6 months with stable MTX doses) were studied for 1 year. RESULTS:
      The mean disease duration and DAS28-ESR score in 75 patients was 7.5 years and
      5.1 at baseline, respectively. The proportion of patients who sustained DAS28-ESR
      <2.6 (48%) and DAS28-ESR <3.2 (62%) for 1 year were significantly lower in the
      ADA discontinuation group than in the ADA continuation group; however, in
      patients with deep remission (DAS28-ESR <=1.98) identified by receiver operating
      characteristics analysis following logistic analysis, these rates increased to
      68% and 79%, respectively, with no significant difference between both groups.
      Remarkably, ADA readministration to patients with flare was effective in
      returning DAS28-ESR to <3.2 within 6 months in 90% and 9 months in 100% patients;
      among the patients who sustained DAS28-ESR <3.2 during ADA discontinuation, 100%
      remained in structural remission and 94% in functional remission. CONCLUSIONS:
      The possibility of remaining ADA-free for 1 year was demonstrated in established
      patients with RA with outcomes that ADA can be discontinued without flaring in
      79% patients with deep remission, with similar rates in the ADA continuation
      group, and showed no functional or structural damage in patients with DAS28-ESR
      <3.2. ADA readministration to patients with flare during ADA discontinuation was
      effective.

PMID- 24288015
TI  - Characterization of a biodegradable coralline hydroxyapatite/calcium carbonate
      composite and its clinical implementation.
AB  - A partially converted, biodegradable coralline hydroxyapatite/calcium carbonate
      (CHACC) composite comprising a coral calcium carbonate scaffold enveloped by a
      thin layer of hydroxyapatite was used in the present study. The CHACC was
      characterized using powder x-ray diffraction, scanning electron microscopy and
      energy dispersive x-ray spectroscopy. The ability of the CHACC to promote
      conductive osteogenesis was assessed in vitro using human mesenchymal stem cells
      (hMSCs) and in vivo using an immunodeficient mouse model. The clinical
      performance of CHACC as a bone substitute to fill voids caused by excision of
      bone tumours was also observed in 16 patients. The CHACC was found to consist of
      two overlapping layers both morphologically and chemically. Hydroxyapatite formed
      a thin layer of nanocrystals on the surface and a thick rough crystal layer of
      around 30 um in thickness enveloping the rock-like core calcium carbonate
      exoskeletal architecture. hMSCs cultured on CHACC in osteogenic medium
      demonstrated significant osteogenic differentiation. After subcutaneous
      implantation of CHACC incorporating osteogenically differentiated hMSCs and an
      anti-resorptive agent, risedronate, into an immunodeficient mouse model, bone
      formation was observed on the surface of the implants. Clinical application of
      CHACC alone in 16 patients for bone augmentation after tumour removal showed that
      after implantation, visible callus formation was observed at one month and
      clinical bone healing achieved at four months. The majority of the implanted
      CHACC was degraded in 18-24 months. In conclusion, CHACC appears to be an
      excellent biodegradable bone graft material. It biointegrates with the host, is
      osteoconductive, biodegradable and can be an attractive alternative to autogenous
      grafts. 

PMID- 24288016
TI  - Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin.
AB  - This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based
      on rapid electrochemical detection. The chemical warfare agent Sarin (C4H10FO2P,
      O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that
      induces rapid respiratory depression, seizures and death within minutes of
      inhalation. As purified Sarin is colourless, odourless, water soluble and a
      easily disseminated nerve agent, it has been used as a weapon in terrorist or
      military attacks. To ascertain whether potable water supplies have been
      adulterated with this extremely potent poison, an inexpensive, sensitive and easy
      to use portable test kit would be of interest to first responders investigating
      such attacks. We report here an amperometric-based approach for detecting trace
      amounts of Sarin in water samples using a screen-printed electrode (SPE)
      integrated in a microfluidic chip. Enzymatic inhibition was obtained by exposing
      the immobilised biosensor in the microfluidic platform to Sarin in water samples.
      With the aid of cobalt phthalocyanine modified SPE, the device could detect Sarin
      at part-per-billion levels with concentration as low as 1 nM. The detection
      method reported here represents a significant improvement over the
      authors'previous optical-based detection method.

PMID- 24288017
TI  - Sinapinic acid-directed synthesis of gold nanoclusters and their application to
      quantitative matrix-assisted laser desorption/ionization mass spectrometry.
AB  - Core etching of gold nanoparticles (AuNPs) into smaller-sized clusters is a
      classic method for fabricating gold nanoclusters (AuNCs). The top down-based
      synthesis of AuNCs includes two steps: (i) reducing the Au(3+) precursor solution
      to generate AuNPs in the presence of protecting ligands and (ii) core etching of
      the formed AuNPs into the AuNCs via ligand exchange. For the first time, this
      paper describes a one-step approach for preparing AuNCs using a top down
      approach. The sinapinic acid (SA)-induced formation of the AuNCs involved a three
      step reaction process. First, large AuNPs (>200 nm) were quickly formed after
      mixing SA and the Au(3+) precursor solution. Second, excess SA molecules self
      assembled on the NP surface, and large AuNPs were etched to small AuNPs via
      electrostatic repulsion between the neighboring SA molecules. Finally, SA-induced
      core etching of the AuNPs resulted in the formation of the AuNCs within 70 min.
      Furthermore, we showed that the presence of the AuNCs in SA was capable of
      suppressing crystal growth and eliminating the coffee-ring effect. Thus, proteins
      can be successfully quantified using the SA-AuNCs as matrices for matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. Compared with using
      SA as matrices, the SA-AuNCs offered substantial advantages for improving shot-to
      shot reproducibility and enhancing the ionization efficiency of proteins. 

PMID- 24288018
TI  - Scrapheap challenge: a novel bulk-bone metabarcoding method to investigate
      ancient DNA in faunal assemblages.
AB  - Highly fragmented and morphologically indistinct fossil bone is common in
      archaeological and paleontological deposits but unfortunately it is of little use
      in compiling faunal assemblages. The development of a cost-effective methodology
      to taxonomically identify bulk bone is therefore a key challenge. Here, an
      ancient DNA methodology using high-throughput sequencing is developed to survey
      and analyse thousands of archaeological bones from southwest Australia. Fossils
      were collectively ground together depending on which of fifteen stratigraphical
      layers they were excavated from. By generating fifteen synthetic blends of bulk
      bone powder, each corresponding to a chronologically distinct layer, samples
      could be collectively analysed in an efficient manner. A diverse range of taxa,
      including endemic, extirpated and hitherto unrecorded taxa, dating back to
      c.46,000 years BP was characterized. The method is a novel, cost-effective use
      for unidentifiable bone fragments and a powerful molecular tool for surveying
      fossils that otherwise end up on the taxonomic "scrapheap". 

PMID- 24288019
TI  - Effect of vocal fold injection of cidofovir and bevacizumab in a porcine model.
AB  - IMPORTANCE: Recurrent respiratory papillomatosis (RRP) is a common and often
      chronic disorder. Intralaryngeal bevacizumab has gained recent interest as an
      adjuvant therapy for RRP. However, no histologic model has been published
      describing the effects of bevacizumab on the vocal fold. OBJECTIVE: To
      investigate the histologic effects of bevacizumab injections into the vocal fold
      and compare these findings with those for cidofovir and saline control
      injections. DESIGN AND SETTING: In vivo animal study involving eighteen 1-year
      old Yorkshire crossbreed pigs, with a blinded review of pathologic findings
      conducted in a veterinary research laboratory. INTERVENTIONS: The pigs were
      randomly divided into six study groups receiving 2.5 or 5.0 mg of cidofovir or
      bevacizumab alone or in combination. Each pig received an injection of 0.5 mL of
      the test drug in the right vocal fold and 0.5 mL of saline in the left vocal
      fold. These injections were performed 4 times during the course of 8 weeks. One
      pig from each group was killed humanely and the larynges harvested 2 weeks after
      the last injection. The remaining pigs were killed 4 months after the last
      injection on the remaining pigs. The vocal folds were fixed and stained with
      hematoxylin-eosin and trichrome and reviewed for histologic changes by 3 blinded
      pathologists. MAIN OUTCOMES AND MEASURES: Histologic changes to the vocal folds.
      RESULTS: Minimal inflammation, edema, and atypia were found in all treatment
      groups. No appreciable histologic differences were found among the 3 treatment
      groups and their controls. No difference was seen in the vocal folds that were
      harvested late (4 months) vs early (2 weeks) after last injection. No fibrosis
      was found in any of the specimens. CONCLUSIONS AND RELEVANCE: No histologic
      evidence suggests that intralaryngeal cidofovir or bevacizumab alone or in
      combination resulted in significant changes to the porcine vocal fold. Future
      studies may build on this model to test higher dosages and/or may combine
      injections with potassium titanyl phosphate laser therapy.

PMID- 24288020
TI  - Five-week use of a monopivot centrifugal blood pump as a right ventricular assist
      device in severe dilated cardiomyopathy.
AB  - Right heart failure is a critical complication in patients requiring mechanical
      ventricular support. However, it is often difficult to provide adequate right
      ventricular support in the acute phase. A 41-year-old woman diagnosed with
      dilated cardiomyopathy with severe right heart failure underwent implantation of
      a paracorporeal pulsatile left ventricular assist device (LVAD, Nipro
      Corporation, Tokyo, Japan) and a MERA monopivot centrifugal pump (Senko Medical
      Instrument Manufacturing Co., Ltd., Tokyo, Japan) as a right ventricular assist
      device (RVAD). The patient developed ischemic enteritis 3 weeks after surgery,
      necessitating fasting and reversal of anticoagulation therapy. A target
      international normalized ratio of 1.5 was selected, and aspirin administration
      was discontinued. Following recovery without thromboembolic events, the patient
      failed the RVAD discontinuation test. Five weeks after surgery, the monopivot
      centrifugal pump was exchanged for a pulsatile pump. No thrombus was evident on
      the centrifugal pump. The patient was undergoing cardiac rehabilitation at the
      time of this writing and awaiting heart transplantation.

PMID- 24288021
TI  - Social support and networks: cardiovascular responses following recall on
      immigration stress among Chinese Americans.
AB  - Social support has been shown to act as a buffer for cardiovascular responses to
      stress. However, little is known about how social support and networks are
      related to cardiovascular responses to immigration stress recall. The current
      study evaluated the impact of structural and functional support on cardiovascular
      reaction following immigrant stress recall provocation as well as the moderation
      effect of interdependent self-construal among first-generation Chinese
      immigrants. One hundred fifty Chinese immigrants were recruited in the New York
      Chinatown area. Participants completed questionnaires assessing their levels of
      social support and networks, and interdependent self-construal. Following
      adaptation, participants recalled a recent post-immigration stress-provoking
      situation. Cardiovascular measures were taken during adaptation, stressor task,
      and recovery period. Hierarchical multiple regression analysis was performed.
      Social network size and type, as well as perceived emotional support were
      positively predictive of systolic blood pressure (SBP) reactivity changes.
      Instrumental support seeking was a positive predictor of SBP and diastolic blood
      pressure (DBP) reactivity. The moderation effect between instrumental support
      seeking and interdependent self-construal were significantly predictive of DBP
      reactivity and recovery, suggesting that perceptions about themselves in relation
      to others is a crucial factor for determining whether support seeking is
      beneficial or not. Social support was not a direct buffer on cardiovascular
      responses to stress among Chinese immigrants. Chinese values of interdependence
      and collectivism may partly explain the disconfirming results. Still, when
      interdependent self-construal was taken into account, Chinese immigrants who had
      less interdependent self-construal, but solicited more instrumental support, had
      faster adaptation to stress over the long term. 

PMID- 24288023
TI  - Performance of short food questions to assess aspects of the dietary intake of
      Australian children.
AB  - Single dietary questions are used as a rapid method of monitoring diet. The aim
      of this investigation was to assess the performance of questions to measure
      population group intake compared to the mean of two 24-h recalls. Data from the
      Australian National Children's Nutrition and Physical Activity Survey 2007 was
      used (n = 4487). Children reported their intake on three questions relating to
      usual serves of fruit, vegetables and type of milk. Age, gender and body weight
      status were assessed as modifiers of the relationship between methods. There was
      a stepwise increase in fruit and vegetable intake (p < 0.001) measured by recall
      when grouped by response category of the short question. By recall, fruit
      consumption decreased with age (F = 12.92, p < 0.001) but this trend was not
      detectable from the short question (F = 2.31, p = 0.075). The difference in fruit
      intake between methods was greatest for obese children. Almost 85% of children
      who consumed whole milk by short question consumed mainly whole fat milk by
      recall, but agreement was lower for other milk types. Saturated fat and volume of
      milk was highest in whole milk consumers. Ease of administration suggests that
      short questions, at least for some aspects of diet, are a useful method to
      monitor population intakes for children. 

PMID- 24288022
TI  - Amino acid profiles in term and preterm human milk through lactation: a
      systematic review.
AB  - Amino acid profile is a key aspect of human milk (HM) protein quality. We report
      a systematic review of total amino acid (TAA) and free amino acid (FAA) profiles,
      in term and preterm HM derived from 13 and 19 countries, respectively. Of the 83
      studies that were critically reviewed, 26 studies with 3774 subjects were
      summarized for TAA profiles, while 22 studies with 4747 subjects were reviewed
      for FAA. Effects of gestational age, lactation stage, and geographical region
      were analyzed by Analysis of Variance. Data on total nitrogen (TN) and TAA
      composition revealed general inter-study consistency, whereas FAA concentrations
      varied among studies. TN and all TAA declined in the first two months of
      lactation and then remained relatively unchanged. In contrast, the FAA glutamic
      acid and glutamine increased, peaked around three to six months, and then
      declined. Some significant differences were observed for TAA and FAA, based on
      gestational age and region. Most regional TAA and FAA data were derived from Asia
      and Europe, while information from Africa was scant. This systematic review
      represents a useful evaluation of the amino acid composition of human milk, which
      is valuable for the assessment of protein quality of breast milk substitutes. 

PMID- 24288024
TI  - Vitamin B(12) and folic acid imbalance modifies NK cytotoxicity, lymphocytes B
      and lymphoprolipheration in aged rats.
AB  - Different vitamin B12 and folic acid concentrations could exacerbate the immune
      response. The aim was to evaluate different dietary folic acid and vitamin B12
      levels on the immune response in aged rats. Male Sprague Dawley aged rats were
      assigned to three folic acid groups (deficient, control, supplemented) each in
      absence of vitamin B12 for 30 days. Several parameters of innate and acquired
      immune responses were measured. Serum and hepatic folate levels increased
      according to folic acid dietary level, while vitamin B12 levels decreased. There
      was a significant decrease in natural killer cell-mediated cytotoxicity in the
      spleen for the vitamin B12 deficient diet and folic acid control diet groups.
      Significant changes in CD45 lymphocyte subsets were also observed according to
      dietary imbalance. Lymphoproliferative response to concanavalin A and
      phytohemagglutinin did not differ significantly between groups. The spleen
      response to lipopolysaccharide increased significantly, but was unmodified for
      the other organs. An imbalance between dietary vitamin B12 and folic acid
      concentrations alters some immunological parameters in aged rats. Therefore, the
      ratio between folate and vitamin B12 could be as important as their absolute
      dietary concentrations. 

PMID- 24288026
TI  - Problems and challenges to adaptation of gluten free diet by Indian patients with
      celiac disease.
AB  - Celiac disease is emerging in India and has become a public health problem.
      Almost 6-8 million Indians are estimated to have celiac disease. While there is a
      large pool of patients with celiac disease in India, until now, only a fraction
      of them have been diagnosed. With increasing awareness about celiac disease
      amongst health care providers and the general population, a massive increase in
      the number of patients with celiac disease is expected now and in the subsequent
      decade in India. While the number of patients with celiac disease is increasing,
      the country's preparedness towards the emerging epidemic of this disease is
      minimal. There are a number of issues, which requires urgent attention. Some of
      the key issues include increased awareness amongst health care professionals and
      the general public about the disease and its management, team-based management of
      patients with celiac disease, proper counseling and supervision of patients,
      training of dietitians in the management of patients with celiac disease,
      industrial production of reliable and affordable gluten-free food, and food
      labeling for gluten contents. 

PMID- 24288025
TI  - Mammalian metabolism of beta-carotene: gaps in knowledge.
AB  - beta-carotene is the most abundant provitamin A carotenoid in human diet and
      tissues. It exerts a number of beneficial functions in mammals, including humans,
      owing to its ability to generate vitamin A as well as to emerging crucial
      signaling functions of its metabolites. Even though beta-carotene is generally
      considered a safer form of vitamin A due to its highly regulated intestinal
      absorption, detrimental effects have also been ascribed to its intake, at least
      under specific circumstances. A better understanding of the metabolism of beta
      carotene is still needed to unequivocally discriminate the conditions under which
      it may exert beneficial or detrimental effects on human health and thus to enable
      the formulation of dietary recommendations adequate for different groups of
      individuals and populations worldwide. Here we provide a general overview of the
      metabolism of this vitamin A precursor in mammals with the aim of identifying the
      gaps in knowledge that call for immediate attention. We highlight the main
      questions that remain to be answered in regards to the cleavage, uptake,
      extracellular and intracellular transport of beta-carotene as well as the
      interactions between the metabolism of beta-carotene and that of other
      macronutrients such as lipids. 

PMID- 24288027
TI  - Calcium-alkali syndrome in the modern era.
AB  - The ingestion of calcium, along with alkali, results in a well-described triad of
      hypercalcemia, metabolic alkalosis, and renal insufficiency. Over time, the
      epidemiology and root cause of the syndrome have shifted, such that the disorder,
      originally called the milk-alkali syndrome, is now better described as the
      calcium-alkali syndrome. The calcium-alkali syndrome is an important cause of
      morbidity that may be on the rise, an unintended consequence of shifts in calcium
      and vitamin D intake in segments of the population. We review the pathophysiology
      of the calcium-alkali syndrome. 

PMID- 24288028
TI  - Phenolic composition, antioxidant activity and anti-adipogenic effect of hot
      water extract from safflower (Carthamus tinctorius L.) seed.
AB  - This study was to evaluate the phenolic content and composition of Carthamus
      tinctorius L. seed extract (CSE) and to further assess its antioxidant and anti
      adipogenic activities using various radical scavenging systems and 3T3-L1 cells.
      Our results show that the total phenolic and flavonoid contents of CSE were 126.0
      +/- 2.4 mg GAE/g and 62.2 +/- 1.9 mg QE/g, respectively. The major phenolic
      compounds in CSE was (-)-epigallocatechin (109.62 mg/g), with a 4-hydroxy
      benzhydrazide derivative and gallocatechin present at 18.28 mg/g and 17.02 mg/g,
      respectively. CSE exhibited remarkable radical scavenging activities, FRAP
      (ferric reducing antioxidant power) and reducing power in a dose-dependent
      manner. Moreover, the oxygen radical absorbance capacity (ORAC) value of CSE (0.1
      mg/mL) was 62.9 +/- 4.7 MUM TE (trolox equivalent)/g. During adipogenesis, CSE
      significantly inhibited fat accumulation in 3T3-L1 cells compared with control
      cells. Overall, these results indicate that CSE might be a valuable source of
      bioactive compounds that impart functional food and natural antioxidant
      properties. 

PMID- 24288029
TI  - Multiplex PCR to detect the genes encoding naturally occurring oxacillinases in
      Acinetobacter spp.
AB  - OBJECTIVES: Bacteria of the genus Acinetobacter are increasingly being isolated
      in hospitals and are recognized as emerging nosocomial pathogens. Species
      identification is difficult and there is a need for simple molecular methods to
      differentiate between the species. Naturally occurring oxacillinase genes
      (blaOXA) have been identified in several Acinetobacter species and their
      detection by PCR can aid in species identification. The aim of this study was to
      develop a multiplex PCR to identify intrinsic blaOXA genes (i.e. bla(OXA-134
      like), bla(OXA-211-like), bla(OXA-213-like), bla(OXA-214-like) and bla(OXA-228
      like)) from Acinetobacter spp. for use as a tool for rapid species
      identification. METHODS: Primers were designed to selectively amplify internal
      fragments of intrinsic blaOXA from Acinetobacter lwoffii/Acinetobacter schindleri
      (bla(OXA-134-like)), Acinetobacter johnsonii (bla(OXA-211-like)), Acinetobacter
      calcoaceticus (bla(OXA-213-like)), Acinetobacter haemolyticus (bla(OXA-214-like))
      and Acinetobacter bereziniae (bla(OXA-228-like)). Multiplex PCR was performed in
      a total of 100 Acinetobacter isolates. Flanking primers were designed for each
      blaOXA subgroup and products were sequenced. RESULTS: All A. lwoffii, A.
      schindleri, A. johnsonii, A. calcoaceticus, A. haemolyticus and A. bereziniae
      isolates were positive for their species-specific amplicons while other
      Acinetobacter species were negative. Thirty blaOXA novel variants were
      identified; the majority of these (21/30) were from A. calcoaceticus. ISAba11 was
      found upstream of bla(OXA-214) in four A. haemolyticus isolates, but was not
      associated with carbapenem resistance. CONCLUSIONS: This multiplex PCR
      specifically detected each of the five different blaOXA subgroups. Therefore,
      this method has the potential to aid in the identification of these species and
      monitor the spread of these genes into other Acinetobacter species.

PMID- 24288030
TI  - Resistance to third-generation cephalosporins in human non-typhoidal Salmonella
      enterica isolates from England and Wales, 2010-12.
AB  - OBJECTIVES: To identify the mechanism(s) underlying cefotaxime resistance in 118
      of 21,641 (0.55%) non-typhoidal Salmonella enterica isolates collected from
      humans throughout England and Wales from January 2010 to September 2012. METHODS:
      Non-duplicate isolates (n = 118) resistant to cefotaxime (MICs >1 mg/L) were
      screened by PCR for genes encoding CTX-M extended-spectrum beta-lactamases
      (ESBLs) and associated ISEcp1-like elements, and for genes encoding acquired
      AmpC, SHV, TEM, VEB, PER and GES beta-lactamases. Sequencing was used to identify
      specific alleles in selected isolates. Carbapenem resistance was sought by
      ertapenem disc screening. RESULTS: Seventy-nine isolates (0.37% of all referred
      S. enterica) produced ESBLs, 37 isolates (0.17%) produced CMY-type AmpC enzymes,
      and 1 isolate had both enzyme types; the mechanism of cefotaxime resistance in 3
      isolates could not be identified. Group 1 CTX-M genes were identified in 57
      isolates belonging to 22 serotypes, with CTX-M-1 (n = 11), -15 (n = 9) and -55/57
      (n = 8) the most prevalent alleles among the 29 (51%) investigated. CTX-M-2 (n =
      5), -14 (n = 5), -8 (n = 1) and -65 (n = 1) were also identified. TEM-52 was
      identified in two isolates and SHV-12 in seven isolates. There was no evidence of
      carbapenem resistance. ESBL and AmpC genes were detected in both domestically
      acquired and travel-associated salmonellae. Eighty-nine isolates (75%) were
      multidrug resistant (resistant to at least three antimicrobial classes) and 42
      (36%) had decreased susceptibility to ciprofloxacin (MICs 0.25-1 mg/L), with a
      further 13 (11%) isolates resistant (MICs >1 mg/L). CONCLUSIONS: The prevalence
      of CTX-M and acquired AmpC genes in human non-typhoidal S. enterica from England
      and Wales is still low, but has increased from 0.03% in 2001-03 to 0.49% in 2010
      12. Resistance to third-generation cephalosporins requires monitoring as it may
      reduce therapeutic options.

PMID- 24288031
TI  - A unified framework for the comparison of treatments with ordinal responses.
AB  - Different latent variable models have been used to analyze ordinal categorical
      data which can be conceptualized as manifestations of an unobserved continuous
      variable. In this paper, we propose a unified framework based on a general latent
      variable model for the comparison of treatments with ordinal responses. The
      latent variable model is built upon the location-scale family and is rich enough
      to include many important existing models for analyzing ordinal categorical
      variables, including the proportional odds model, the ordered probit-type model,
      and the proportional hazards model. A flexible estimation procedure is proposed
      for the identification and estimation of the general latent variable model, which
      allows for the location and scale parameters to be freely estimated. The
      framework advances the existing methods by enabling many other popular models for
      analyzing continuous variables to be used to analyze ordinal categorical data,
      thus allowing for important statistical inferences such as location and/or
      dispersion comparisons among treatments to be conveniently drawn. Analysis on
      real data sets is used to illustrate the proposed methods. 

PMID- 24288032
TI  - Clinical and ultrasonographic measurement of liver size in normal children.
AB  - OBJECTIVES: To measure the normal range of dimensions of liver in children of
      various age groups and to compare the liver measurement obtained by palpation
      percussion, auscultation and ultrasonography. METHODS: This was a cross-sectional
      comparative study in which 500 normal (weight for height between +/- 2 SD of WHO
      standards for children aged less than 5 y and BMI between +/- 2 SD of WHO
      standards for children aged more than 5 y) children (0-15 y) divided in 5 age
      groups (100 in each age group). Subjects were enroled from normal hospital
      delivery neonates, children visiting immunization and well baby clinics, children
      visiting outpatient and inpatient department with minor illnesses and healthy
      school children. RESULTS: The normal range of dimensions of liver in children
      were estimated and percentile tables of liver size were established. Though the
      measurements obtained by clinical methods were significantly (P < 0.001) lower
      than those obtained by ultrasonography, there was a strong correlation between
      clinical and ultrasonographic measurement. Palpation-percussion method could
      estimate the liver size within +/- 1.0 cm of what was obtained by ultrasonography
      in 88 % of cases. In more than half of the study children (54.2 %), this
      estimation was within +/- 0.5 cm. CONCLUSIONS: Clinical methods of liver span
      estimation strongly correlate with ultrasonographic measurement. The performance
      of palpation-percussion method is better than that of auscultation. Clinical
      methods should continue to be used for the estimation of liver size.

PMID- 24288033
TI  - Recurrence of Angelman syndrome in siblings: challenges in genetic counseling.
AB  - The authors report a rare occurrence of two siblings with Angelman syndrome.
      Their karyotype revealed monosomy of chromosome 15 and a derivative chromosome 1
      leading to Angelman syndrome. Their mother was a balanced translocation carrier
      involving chromosomes 1p and 15p. In her subsequent pregnancy, prenatal karyotype
      analysis was offered and the fetus was unaffected. 

PMID- 24288034
TI  - Structure-property relationship of anilino-squaraines in organic solar cells.
AB  - Soluble molecular semiconductors are a promising alternative to semiconducting
      polymers in the field of organic photovoltaics. Here, three custom-made symmetric
      1,3-bis(N,N-alkylated-2,6-dihydroxy-anilino)squaraines containing systematic
      variations in their molecular structures are compared regarding their
      applicability as donor materials in bulk-heterojunction solar cells. The terminal
      substitution pattern of the squaraines is varied from cyclic over linear to
      branched including a stereogenic center. Single crystal structures are
      determined, and, in the case of chiral squaraine, unusual formation of
      stereoisomer co-crystals is revealed. The thin film absorbance spectra show
      characteristic signatures of H- and J-bands or hint at the formation of
      tautomers. The general feasibility of these model compounds for photovoltaic
      applications is studied by light-induced electron spin resonance spectroscopy.
      The impact of the different molecular substitution patterns on aggregation
      behavior and, consequently, their optoelectronic solid state properties including
      charge carrier mobility and finally the solar cell performance are investigated. 

PMID- 24288036
TI  - Experiencing extinction within a task makes nonextinguished information learned
      within a different task context-dependent.
AB  - In two experiments with rats, we analyzed the effect of experiencing extinction
      in one task on the context specificity of a new association learned within a
      different task. Rats were trained to run in a runway for water in Task 1, and
      received taste aversion conditioning in Task 2 (the tasks were reversed in Exp.
      2). Half of the rats received conditioning and extinction of Task 1 in Context A,
      whereas the other half received no extinction. Then all animals received training
      in the alternate task in Context B, prior to testing in Context C. When they were
      tested in Context C, Task 2 performance was attenuated if Task 1 had been
      extinguished prior to Task 2. These results are similar to those we have reported
      in humans, and consistent with the idea that extinction prompts attention to
      contexts, regardless of whether or not the contexts were involved in extinction. 

PMID- 24288035
TI  - Treatment of cognitive, psychiatric, and affective disorders associated with
      Parkinson's disease.
AB  - Neuropsychiatric symptoms are common in Parkinson's disease (PD) and add
      significantly to the burden of disease. These symptoms are most commonly part of
      the disease spectrum owing to pathological changes within relevant brain regions.
      Neuropsychiatric problems include disorders of cognition, ranging from mild
      cognitive impairment to dementia, psychotic symptoms, including, most commonly,
      well-formed visual hallucinations and paranoid delusions, and mood disorders,
      such as depression and anxiety. The other common cause of neuropsychiatric
      problem is secondary to use of dopaminergic drugs. Some PD patients may develop
      behavioral disorders, including impulse control disorders (ICDs) and addictive
      symptoms. Psychosis can be due to a mixture of underlying pathology, with
      triggering or worsening of symptoms with changes to PD medications. Currently,
      management of these disorders primarily uses therapies developed for general
      psychiatry and cognitive neurology, rather than specifically for PD. However,
      significant adverse effects, such as worsening of the motor symptoms of PD, can
      limit use of some drug therapies. Identification of drug-induced symptoms, such
      as ICDs, enables withdrawal of the offending drug as the principal management
      strategy. Research is ongoing in an effort to develop more specific therapies for
      PD-related neuropsychiatric symptoms. 

PMID- 24288037
TI  - Dietary triheptanoin rescues oligodendrocyte loss, dysmyelination and motor
      function in the nur7 mouse model of Canavan disease.
AB  - The inherited pediatric leukodystrophy Canavan disease is characterized by
      dysmyelination and severe spongiform degeneration, and is currently refractory to
      treatment. A definitive understanding of core disease mechanisms is lacking, but
      pathology is believed to result at least in part compromised fatty acid synthesis
      during myelination. Recent evidence generated in an animal model suggests that
      the breakdown of N-acetylaspartate metabolism in CD results in a heightened
      coupling of fatty acid synthesis to oligodendrocyte oxidative metabolism during
      the early stages of myelination, thereby causing acute oxidative stress. We
      present here the results of a dietary intervention designed to support oxidative
      integrity during developmental myelination in the nur7 mouse model of Canavan
      disease. Provision of the odd carbon triglyceride triheptanoin to neonatal nur7
      mice reduced oxidative stress, promoted long-term oligodendrocyte survival, and
      increased myelin in the brain. Improvements in oligodendrocyte survival and
      myelination were associated with a highly significant reduction in spongiform
      degeneration and improved motor function in triheptanoin treated mice. Initiation
      of triheptanoin treatment in older animals resulted in markedly more modest
      effects on these same pathological indices, indicating a window of therapeutic
      intervention that corresponds with developmental myelination. These results
      support the targeting of oxidative integrity at early stages of Canavan disease,
      and provide a foundation for the clinical development of a non-invasive dietary
      triheptanoin treatment regimen. 

PMID- 24288039
TI  - Base-free hydrogen generation from methanol using a bi-catalytic system.
AB  - A bi-catalytic system, in which Ru-MACHO-BH and Ru(H)2(dppe)2 interact in a
      synergistic manner, was developed for the base-free dehydrogenation of methanol.
      A total TON > 4200 was obtained with only trace amounts of CO contamination (<8
      ppm) in the produced gas. 

PMID- 24288038
TI  - Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for
      diagnosis and management.
AB  - Abetalipoproteinemia (ABL; OMIM 200100) and homozygous hypobetalipoproteinemia
      (HHBL; OMIM 107730) are rare diseases characterized by hypocholesterolemia and
      malabsorption of lipid-soluble vitamins leading to retinal degeneration,
      neuropathy and coagulopathy. Hepatic steatosis is also common. The root cause of
      both disorders is improper packaging and secretion of apolipoprotein (apo) B
      containing lipoprotein particles due to mutations either in both alleles of the
      MTP (alias MTTP) gene encoding microsomal triglyceride transfer protein (MTP) or
      both alleles of the APOB gene itself in the case of ABL and HHBL, respectively.
      Clinical diagnosis is based on signs and symptoms, acanthocytosis on blood smear,
      and virtually absent apo B-containing lipoproteins, including chylomicrons, very
      low density lipoprotein and low density lipoprotein. Obligate heterozygote
      parents of ABL patients usually have normal lipids consistent with autosomal
      recessive inheritance, while heterozygous parents of HHBL patients typically have
      half normal levels of apo B-containing lipoproteins consistent with autosomal co
      dominant inheritance. Definitive diagnosis involves sequencing the MTP and APOB
      genes, for which >30 and >60 mutations have been described for ABL and HHBL,
      respectively. Follow-up includes monitoring for ophthalmologic, neurologic,
      hematologic, and hepatic complications, as well as compliance with treatment.
      Investigations include lipid profile, serum transaminases, markers for lipid
      soluble vitamins, and periodic instrumental assessment of ocular and neurological
      function. Mainstays of treatment include adherence to a low-fat diet, and
      supplementation with essential fatty acids and high oral doses of fat soluble
      vitamins. Prognosis is variable, but early diagnosis and strict adherence to
      treatment can recover normal neurological function and halt disease progression. 

PMID- 24288040
TI  - Germination and root elongation bioassays in six different plant species for
      testing Ni contamination in soil.
AB  - In vitro short-term chronic phytotoxicity germination and root elongation test
      were applied to test the effects of nickel (Ni) in seed germination and root
      elongation in six plants species: Cucumis sativus (Cucurbitaceae), Lepidium
      sativum and Brassica nigra (Brassicaceae), Trifolium alexandrinum and Medicago
      sativa (Fabaceae), Phacelia tanacetifolia (Boraginaceae). A naturally Ni rich
      soil was used to compare the results obtained. Unlike root elongation,
      germination was not affected by Ni in any of the six species tested. EC50 values,
      calculated on the root elongation, showed that Ni toxicity decreases in the
      following order: P. tanacetifolia > B. nigra > C. sativus > L. sativum > M.
      sativa > T. alexandrinum. The test conducted using soil elutriate revealed a
      significantly lower effect in both seed germination and root elongation when
      compared to the results obtained using untreated soil. Conversely, the test
      performed on soil confirmed the high sensitivity of C. sativus, P. tanacetifolia
      and L. sativum to Ni.

PMID- 24288042
TI  - Anti-HCV RNA Aptamers Targeting the Genomic cis-Acting Replication Element.
AB  - Hepatitis C virus (HCV) replication is dependent on the existence of several
      highly conserved functional genomic RNA domains. The cis-acting replication
      element (CRE), located within the 3' end of the NS5B coding region of the HCV
      genome, has been shown essential for efficient viral replication. Its sequence
      and structural features determine its involvement in functional interactions with
      viral RNA-dependent RNA polymerase and distant RNA domains of the viral genome.
      This work reports the use of an in vitro selection strategy to select aptamer RNA
      molecules against the complete HCV-CRE. After six selection cycles, five
      potential target sites were identified within this domain. Inhibition assays
      using a sample of representative aptamers showed that the selected RNAs
      significantly inhibit the replication (>80%) of a subgenomic HCV replicon in Huh
      7 cell cultures. These results highlight the potential of aptamer RNA molecules
      as therapeutic antiviral agents. 

PMID- 24288041
TI  - New strategies to develop novel pain therapies: addressing thermoreceptors from
      different points of view.
AB  - One approach to develop successful pain therapies is the modulation of
      dysfunctional ion channels that contribute to the detection of thermal,
      mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs,
      promote the sensitization and activation of primary sensory neurons known as
      nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have
      validated these channels as therapeutic targets for pain intervention. Several
      thermoTRP modulators have progressed towards clinical development, although most
      failed because of the appearance of unpredicted side effects. Thus, there is yet
      a need to develop novel channel modulators with improved therapeutic index. Here,
      we review the current state-of-the art and illustrate new pharmacological
      paradigms based on TRPV1 that include: (i) the identification of activity
      dependent modulators of this thermoTRP channel; (ii) the design of allosteric
      modulators that interfere with protein-protein interaction involved in the
      functional coupling of stimulus sensing and gate opening; and (iii) the
      development of compounds that abrogate the inflammation-mediated increase of
      receptor expression in the neuronal surface. These new sites of action represent
      novel strategies to modulate pathologically active TRPV1, while minimizing an
      effect on the TRPV1 subpopulation involved in physiological and protective roles,
      thus increasing their potential therapeutic use. 

PMID- 24288043
TI  - Potential Use of Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel
      Carriers for siRNA.
AB  - Cyclodextrin (CyD)-based nanoparticles and polyamidoamine (PAMAM) starburst
      dendrimers (dendrimers) are used as novel carriers for DNA and RNA. Recently,
      small interfering RNA (siRNA) complex with beta-CyD-containing polycations (CDP)
      having adamantine-PEG or adamantine-PEG-transferrin underwent a phase I study for
      treatment of solid tumors. Multifunctional dendrimers can be used for a wide
      range of biomedical applications, including the interaction and intracellular
      delivery of DNA and RNA. The present review will address the latest developments
      in dendrimer conjugates with cyclodextrins for siRNA delivery including the novel
      sustained release system. 

PMID- 24288044
TI  - 89Zr-Radiolabeled Trastuzumab Imaging in Orthotopic and Metastatic Breast Tumors.
AB  - The human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in 20
      30% of breast cancers and is associated with tumor growth, angiogenesis, and
      development of distant metastases. Trastuzumab, an anti-HER2 monoclonal antibody,
      is used for the treatment of HER2 positive breast cancer and clinical efficacy of
      this agent is dependent on HER2 expression. Targeted PET imaging of HER2 with
      radiolabeled trastuzumab may be used to determine HER2 expression levels and
      guide therapy selection. The purpose of the current study was to evaluate a
      facile 89Zr-trastuzumab preparation method that can be efficiently applied for
      clinical grade production. Also, relative HER2 expression levels in orthotopic
      and metastatic breast cancer models were assessed by PET imaging using the 89Zr
      trastuzumab produced by this simpler method. 

PMID- 24288046
TI  - Survey about tolerance of the AS03-adjuvanted H1N1 influenza vaccine in children
      with rheumatic diseases.
AB  - The objective of this study is to evaluate complications and changes in health
      status (disease activity and flare) in response to the AS03-adjuvanted H1N1
      vaccine in children with rheumatic diseases. We conducted a nationwide survey
      addressing paediatric rheumatology sites who participated in the national
      paediatric rheumatology database. Ninety patients were documented-38 % under
      treatment with biologicals-of whom 18 % suffered from complications (10 % local
      and 8 % systemic) with no relevant changes in median disease activity or flare
      rate during 4 weeks following the vaccination. The adjuvanted H1N1 influenza
      vaccine seems to be adequately tolerated in children with rheumatic diseases. 

PMID- 24288045
TI  - DNA methylation as clinically useful biomarkers-light at the end of the tunnel.
AB  - A recent expansion of our knowledge about epigenetic changes strongly suggests
      that epigenetic rather than genetic features better reflect disease development,
      and consequently, can become more conclusive biomarkers for the detection and
      diagnosis of different diseases. In this paper we will concentrate on the current
      advances in DNA methylation studies that demonstrate a direct link between
      abnormal DNA methylation and a disease. This link can be used to develop
      diagnostic biomarkers that will precisely identify a particular disease. It also
      appears that disease-specific DNA methylation patterns undergo unique changes in
      response to treatment with a particular drug, thus raising the possibility of DNA
      methylation-based biomarkers for the monitoring of treatment efficacy, for
      prediction of response to treatment, and for the prognosis of outcome. While
      biomarkers for oncology are the most obvious applications, other fields of
      medicine are likely to benefit as well. This potential is demonstrated by DNA
      methylation-based biomarkers for neurological and psychiatric diseases. A special
      requirement for a biomarker is the possibility of longitudinal testing. In this
      regard cell-free circulating DNA from blood is especially interesting because it
      carries methylation markers specific for a particular disease. Although only a
      few DNA methylation-based biomarkers have attained clinical relevance, the
      ongoing efforts to decipher disease-specific methylation patterns are likely to
      produce additional biomarkers for detection, diagnosis, and monitoring of
      different diseases in the near future. 

PMID- 24288047
TI  - Gender differences in Iranian patients with ankylosing spondylitis.
AB  - Inequalities in features and severity of ankylosing spondylitis (AS) have been
      noticed between men and women, suggesting a possible influence of gender on
      disease phenotypes. Comparing disease features and characterization of gender
      differences in clinical features and medications could help elucidate the
      potential influence of gender on the severity of AS in patients. This study aims
      to assess the influence of gender on disease patterns in Iranian patients with
      AS. Three hundred and twenty patients diagnosed with primary AS were assessed for
      demographic variables, clinical manifestations, HLA status, disease severity,
      functional capacities, quality of life, and treatment status. Sixty-seven women
      and 253 men were included corresponding to a male to female ratio of 3.78:1. Both
      groups were similar regarding ethnicity, positive family history, and juvenile
      onset AS. HLA-B27 was more frequent among males (78.3 vs. 55.2%; p < 0.001).
      There was a higher proportion of female patients with overall enthesitis (p <
      0.05). Extra-articular manifestations and treatment modalities presented similar
      frequencies in both genders. No difference in gender-associated diagnostic delays
      was observed. Female disease was at least as severe as male disease, and in some
      aspects, females presented with more severe disease. Despite a relatively similar
      disease profile, we observed a higher rate of enthesitis among women. Together
      with the equally high rate of disease activity indices in both genders, these
      findings indicate an overall longer delay to diagnosis in our country. Early
      detection and specialized care would be of great practical importance.

PMID- 24288048
TI  - Choosing a fellow or fellowship: a survey of pediatric otolaryngologists.
AB  - IMPORTANCE: The numbers of pediatric otolaryngology fellowship programs and
      applicants have increased over the past 5 years. However, the qualities desired
      in programs and applicants have not been explored. OBJECTIVE: To determine the
      factors that fellowship program directors and applicants believe to be most
      important in choosing a fellow and the factors most important to fellowship
      applicants in choosing a program. DESIGN, SETTING, AND PARTICIPANTS: Cohort study
      using an anonymous online survey of 2012 pediatric otolaryngology fellowship
      program directors and applicants. Respondents were asked to rank a list of 10
      qualities from most to least important for judging the strength of a fellowship
      applicant. Applicants also assessed the importance of factors in choosing a
      fellowship. MAIN OUTCOMES AND MEASURES: Rank of each factor by members of each
      group. RESULTS: Thirty-two of 47 applicants (68%) and 15 of 31 fellowship
      directors (48%) completed the survey. For applicants, the most important factors
      when choosing a fellowship program were gaining strong experience in airway
      management and otology, faculty reputation, and location, whereas Accreditation
      Council for Graduate Medical Education (ACGME) accreditation, fellowship
      longevity, and salary were less important. For choosing an applicant, applicants
      indicated that the interview, prior applicant knowledge (trusted recommendation),
      and letters of recommendation, sequentially, should be given the greatest weight.
      Directors reported that they used the same top 3 factors to rank applicants, but
      knowledge or trusted recommendation of the applicant ranked first. Applicants who
      successfully matched interviewed at (mean, 9.5 vs 3.0; P = .003), applied at
      (mean, 11.6 vs 4.3; P = .02), and ranked (mean, 8.3 vs 2.3; P < .001) more
      fellowship programs than those who did not. United States Medical Licensing
      Examination scores higher than 230 and AOmegaA membership status did not
      significantly affect fellowship match. CONCLUSIONS AND RELEVANCE: Personal
      knowledge or a trusted colleague's recommendation may be the most important
      determinant when pediatric otolaryngology fellowship programs choose an
      applicant. When fellows choose a program, the opportunity to gain surgical
      experience in both otology and airway management is crucial, but ACGME
      accreditation status seems less important. Successful applicants ranked and
      interviewed at more fellowship programs than nonmatching applicants.

PMID- 24288049
TI  - Relationships between uterus and eggs in cestodes from different taxa, as
      revealed by scanning electron microscopy.
AB  - Uterine organization and interaction with developing eggs in Tetrabothrius
      erostris (Tetrabothriidea), Nippotaenia mogurndae (Nippotaeniidea), Arostrilepis
      tenuicirrosa, and Monocercus arionis (Cyclophyllidea), cestodes belonging to
      three different orders, were investigated by scanning electron microscopy. The
      interactions were traced from sexually mature to gravid proglottids for all
      species. Pieces of evidence of interactions among these species include specific
      tight contacts between microlamellae of the uterine epithelium and the egg
      capsule, networks of fibrils between eggs and uterus, or numerous branched
      diverticula of the uterine wall that surround eggs or combinations of these. The
      contacts between uterine epithelium and eggs take place in mature and post-mature
      proglottids, at a period of development when eggs are newly formed and the
      embryos are rapidly developing. The eggs grow and develop actively in tight
      contact with the uterine wall. The maximum diameter of eggs increases 1.5-2 times
      (or 3.5-4 times in M. arionis) during development. In all species, the intimate
      contacts between uterus and eggs have weakened or disappeared by the time the
      proglottids have become gravid. The association between uterus and eggs thus
      appears as strong evidence of active trophic interaction (or matrotrophy) between
      the parent organism and developing eggs. 

PMID- 24288051
TI  - Laurel leaf extracts for honeybee pest and disease management: antimicrobial,
      microsporicidal, and acaricidal activity.
AB  - A diverse set of parasites and pathogens affects productivity and survival of
      Apis mellifera honeybees. In beekeeping, traditional control by antibiotics and
      molecules of synthesis has caused problems with contamination and resistant
      pathogens. In this research, different Laurus nobilis extracts are tested against
      the main honeybee pests through an integrated point of view. In vivo effects on
      bee survival are also evaluated. The ethanol extract showed minimal inhibitory
      concentration (MIC) values of 208 to 416 MUg/mL, having the best antimicrobial
      effect on Paenibacillus larvae among all substances tested. Similarly, this leaf
      extract showed a significant antiparasitic activity on Varroa destructor, killing
      50 % of mites 24 h after a 30-s exposure, and on Nosema ceranae, inhibiting the
      spore development in the midgut of adult bees ingesting 1 * 10(4) MUg/mL of
      extract solution. Both ethanol extract and volatile extracts (essential oil,
      hydrolate, and its main component) did not cause lethal effects on adult
      honeybees. Thus, the absence of topical and oral toxicity of the ethanol extract
      on bees and the strong antimicrobial, microsporicidal, and miticidal effects
      registered in this study place this laurel extract as a promising integrated
      treatment of bee diseases and stimulates the search for other bioactive
      phytochemicals from plants.

PMID- 24288050
TI  - The Gyrodactylus (Monogenea, Gyrodactylidae) parasite fauna of freshwater sand
      gobies (Teleostei, Gobioidei) in their centre of endemism, with description of
      seven new species.
AB  - While Gobioidei comprises showcases of (adaptive) radiation, the scientific
      interest they yielded did not ensure full understanding of goby biodiversity.
      Even in a well-studied region like Europe, wide knowledge gaps remain. Sand
      gobies represent one of the few clades whose monogenean parasites have been
      thoroughly studied. However, in the Balkans, part of the sand gobies' centre of
      endemism, these parasites were unstudied. We focus on Greek and Croatian
      freshwater gobies. From five sand goby species, the first parasites are reported,
      describing seven new Gyrodactylus species. Economidichthys pygmaeus harbours
      Gyrodactylus benedeni sp. n. and Gyrodactylus dorlodoti sp. n. Its congener E.
      trichonis hosts G. meelkopae sp. n. Knipowitschia milleri was found to host G.
      charon sp. n., K. thessala is infected by G. bios sp. n., and K. croatica by G.
      douglasadamsi sp. n. and G. hellemansi sp. n. Gyrodactylus bubyri was found on
      its type host K. caucasica. A diverse parasite fauna is expected for a region
      known for its biodiversity and endemism. The contribution of parasites to species
      richness in such hotspots is overlooked. The observed species richness per host
      is rather low compared to the better-studied eastern Atlantic sand gobies. Host
      vicariance is considered to mediate parasite specificity in this fauna. Some new
      flatworm species display unique morphological features, such as the remarkable
      size of the marginal hook sickle proper compared to its foot in the
      Economidichthys parasites, or a characteristically kinked marginal hook sickle in
      G. douglasadamsi sp. n. These features reflect their hosts' endemism in the
      Balkans.

PMID- 24288052
TI  - Adult of Dirofilaria repens in a dog with recurrent multiple subcutaneous nodular
      lesions.
AB  - Subcutaneous dirofilariosis is a zoonosis parasitizing the dog, transmitted by
      Culicidae mosquitoes. An increasing number of new cases have been reported both
      in dogs and in humans all over the world. The aim of this work was to describe an
      uncommon case of recurrent multiple subcutaneous nodules by Dirofilaria repens in
      a 2-year-old dog. Surgical excision of two nodules on both hind limbs revealed a
      single thread-like live nematode and multiple parasite fragments, respectively.
      The parasite was morphologically identified as an adult female of D. repens.
      Haematoxylin-eosin tissue sections of nodules revealed a diffuse pyogranulomatous
      angiocentric dermatitis with an intense eosinophilic infiltrate throughout the
      dermis. One month post-surgery, a new nodular lesion was detected on the right
      thigh and resolved spontaneously in a few weeks. During the following 3 months,
      two other nodules were briefly noted both on the right hip and on the left side
      of the chest. The dog was periodically treated with milbemycin oxime and
      praziquantel, starting a week before the appearance of the first nodule.
      Microfilariae were not detected neither in the bloodstream nor in fine-needle
      aspirates at any time, and the diagnosis was made only after surgery.
      Practitioners should consider dirofilariosis in the differential diagnosis of
      subcutaneous swellings, especially if they have a recurrent behaviour, previously
      described in humans but not in dogs.

PMID- 24288053
TI  - Acaricidal activity of extract of Artemisia absinthium against Rhipicephalus
      sanguineus of dogs.
AB  - The objective of the study was to evaluate the in vitro efficacy of different
      concentrations of chloroform extract obtained from the aerial parts of Artemisia
      absinthium in comparison to amitraz on adults, eggs and larvae of the dog tick
      Rhipicephalus sanguineus using the adult immersion test (AIT), egg hatchability
      test (EHT) and larval packet test (LPT), respectively. Five concentrations of the
      extract (1.25, 2.5, 5, 10 and 20 %) with three replications for each
      concentration were used in all the bioassays. A control group was established
      (water + dimethylsulphoxide) together with a positive control group (amitraz),
      with three repetitions each. In AIT, the mortality rates were 0.0, 13.3, 16.7,
      33.3 and 93.3 % in concentrations of 1.25, 2.5, 5, 10 and 20 %, respectively, and
      the variation was significant (p=0.0151). The LC50 (CI) and LC95 (CI) values were
      calculated as 8.793 % (8.217-9.408) and 34.59 % (29.71-40.26), respectively. The
      egg production was reduced by 6.6, 6.6, 18.3, 42.5 and 85.1 % in the
      concentrations of 1.25, 2.5, 5, 10 and 20 %, respectively, and it was
      statistically significant (p=0.0274). In EHT, hatching was completely inhibited
      at 5, 10 and 20 % displaying 100 % ovicidal action while at the concentrations of
      1.25 and 2.5 %, the inhibition rates were 20 and 60 %, respectively. In LPT, the
      extract caused 100 % mortality of larvae in the concentrations of 5, 10 and 20 %
      after 24 h while at the concentrations of 1.25 and 2.5 %, the mortality rates
      were 54.3 and 96.7 %, respectively. The LC50 (CI) and LC95 (CI) values were
      determined to be 1.11 % (1.099-1.121) and 2.37 % (2.328-2.423), respectively. The
      results show that the extract of A. absinthium has acaricidal properties and
      could be useful in controlling R. sanguineus which is an efficient vector of
      pathogens both in dogs and humans.

PMID- 24288054
TI  - Relationship between self-reported disability and functional capacity in patients
      with whiplash associated disorder.
AB  - PURPOSE: Patients with chronic Whiplash Associated Disorders (WAD) report
      symptoms and disability. Neither the relationship between self-reported
      disability and functional capacity, nor its predictors have been investigated in
      patients with WAD. This was the purpose of this study. METHOD: This was a cross
      sectional study. Participants were patients with WAD on sick leave. Self-reported
      disability was assessed with the Neck Disability Index (NDI). Functional capacity
      was assessed with a six-item neck functional capacity evaluation (FCE).
      Correlation coefficients were used to express the relationship between NDI (total
      and items) and FCE. Multivariate linear regression analyses were performed to
      identify independent predictors of NDI and FCE. RESULTS: Forty patients were
      measured, of whom 18 (45 %) were male. Mean age was 33 years, median duration of
      complaints was 12 months, and 75 % had a pending insurance claim. Correlations
      between NDI and FCE tests varied from -0.39 to -0.70. Independent predictors of
      NDI were pain intensity and a pending claim, explaining 43 % of the variance.
      independent predictors of fce were ndi, gender, and pain intensity, explaining 20
      55 % of the variance. CONCLUSIONS: Self-reported disability and functional
      capacity are related but different. Both can part be predicted by pain intensity.
      A pending claim can predict higher self-reported disability. Both constructs are
      complementary and are recommended to determine disability in patients with WAD
      comprehensively.

PMID- 24288055
TI  - Direct detection of ultralow trace amounts of isocyanates in air using a
      fluorescent conjugated polymer.
AB  - A fluorescence sensory polymer containing the pentiptycene and
      tetraphenylethylene units linked by acetylene was synthesized for direct
      detection of isocyanates in air. Eight industrially available aliphatic and
      aromatic isocyanates were tested. The polymer film shows a rapid fluorescence
      quenching response to any type of isocyanates with a ppt level of detection
      limit, which is much lower than the permissible exposure limit of 5 ppb. 

PMID- 24288056
TI  - SOX7: from a developmental regulator to an emerging tumor suppressor.
AB  - SOX7 belongs to the SOX (SRY-related HMG-box) family of transcription factors
      that have been shown to regulate multiple biological processes, such as
      hematopoiesis, vasculogenesis and cardiogenesis during embryonic development.
      Recent studies indicate that several SOX family members play important roles in
      tumorigenesis. In this review, we introduce SOX7 gene and protein structures, and
      discuss its expression and functional role in cancer development and progression.
      SOX7 is frequently downregulated in many human cancers and its reduced expression
      correlates with poor prognoses of several cancers. Functional studies reveal many
      tumor suppressive properties of SOX7 in prostate, colon, lung, and breast
      cancers. To date, although a few target genes of SOX7 have been identified, SOX7
      mediated gene expression has not been investigated in a cancer-relevant context.
      Our recent studies not only for the first time demonstrate a tumor suppressive
      role of SOX7 in a xenograft mouse model, but also unravel that many genes
      regulating cell death, growth and apoptosis are affected by SOX7, strongly
      supporting a pivotal role of SOX7 in tumorigenesis. Thus, currently available
      data clearly indicate a tumor suppressive role of SOX7, but the mechanisms
      underlying its gene expression and tumor suppressive activity remain
      undetermined. The research of SOX7 in cancers remains a fertile area to be
      explored.

PMID- 24288057
TI  - Adaptive response of poplar (Populus nigra L.) after prolonged Cd exposure
      period.
AB  - An outdoor pot experiment was designed to study the changes of growth parameters,
      accumulation, and distribution of Cd in poplar (Populus nigra L.) during a
      prolonged exposure period (growing period of 17 months including three harvest
      points), allowing the consideration of time effects and prolonged adaptation to
      Cd stress. Simultaneously, changes to the antioxidant system in roots and leaves
      were monitored. It was demonstrated that poplar could adapt to the Cd
      contaminated soils after prolonged exposure. Total Cd accumulation in the aerial
      parts of poplar, due to high biomass production and acceptable Cd accumulation
      parameters, implies that the tested poplar species could be a good candidate for
      Cd phytoextraction application as well as could be used as phytostabilizer of Cd
      in heavily polluted soil. Furthermore, the activity of the antioxidant machinery
      displays both a tissue- and exposure-specific response pattern to different Cd
      treatments, indicating that strict regulation of the antioxidant defense system
      is required for the adaptive response of poplar. In addition, this report
      highlights the importance of prolonged exposure studies of physiological
      responses of plants, especially for long-life-cycle woody species under heavy
      metal stress, since some misleading conclusions could be reached after shorter
      time periods.

PMID- 24288059
TI  - Using Bayesian optimization method and FLEXPART tracer model to evaluate CO
      emission in East China in springtime.
AB  - Carbon monoxide (CO) is of great interest as a restriction factor for pollutants
      related to incomplete combustions. This study attempted to evaluate CO emission
      in East China using the analytical Bayesian inverse method and observations at
      Mount Hua in springtime. The mixing ratio of CO at the receptor was calculated
      using 5-day source-receptor relationship (SRR) simulated by a Lagrangian Particle
      Dispersion Model (FLEXPART) and CO emission flux. The stability of the inversion
      solution was evaluated on the basis of repeated random sampling simulations. The
      inversion results demonstrated that there were two city cluster regions (the
      Beijing-Tianjin-Hebei region and the low reaches of the Yangtze River Delta)
      where the difference between a priori (Intercontinental Chemical Transport
      Experiment-Phase B, INTEX-B) and a posteriori was statistically significant and
      the a priori might underestimate the CO emission flux by 37 %. A correction
      factor (a posteriori/a priori) of 1.26 was suggested for CO emission in China in
      spring. The spatial distribution and magnitude of the CO emission flux were
      comparable to the latest regional emission inventory in Asia (REAS2.0).
      Nevertheless, further evaluation is still necessary in view of the larger
      uncertainties for both the analytical inversion and the bottom-up statistical
      approaches.

PMID- 24288060
TI  - Phosphorus-31 nuclear magnetic resonance assignments of biogenic phosphorus
      compounds in sediment of an artificial Fuyangxin River, China.
AB  - River eutrophication could drastically influence the phosphorus (P) in the water
      and sediment. To understand the biogenic-P species, distribution and
      bioconversion, five sediment samples were collected from an artificial river, and
      analyzed by phosphorus-31 nuclear magnetic resonance ((31)P-NMR). The P pollution
      in the water and sediment were both severe. The average concentrations of total P
      (TP) and solution reactive phosphorus in the water were 3.0 and 2.6 mg L(-1),
      respectively, which surpass grade V of the national quality standard (China) and
      should not be used for any purpose. The river sediments accumulated significant
      inorganic phosphorus (Pi) and organic phosphorus (Po); in the P fractionation,
      the rank order of the P fractions was as follows: Ca-P > NaOH-Pi > Res-P > KCl-P
      > NaOH-Po, with average relative proportions of 25.1:16.8:6.6:1.7:1:0. Six P
      compounds were detected in the NaOH-EDTA extract by (31)P-NMR. Mono-P (8.96-29.58
      %) was the dominant forms of biogenic-P, and other smaller fractions of biogenic
      P were also observed, including pyro-P (0.22-0.86 %), DNA-P (0.75-2.03 %), phon-P
      (0-1.57 %), and lipids-P (0-2.66 %). The TP and biogenic-P decreased along the
      direction of flows, with their average relative proportions
      7.97:1.20:1.49:1.00:1.00 and 40.87:2.34:3.46:1.60:1 from the upstream to
      downstream, respectively. The concentration and species of Po in NaOH-Po were
      lower than found in (31)P-NMR analysis in this research. Thus, the use of 0.25 M
      NaOH and 50 mM EDTA extracts and solution (31)P-NMR analysis was a more accurate
      method for quantifying biogenic-P in the river sediments than P fractionation.

PMID- 24288061
TI  - Response of the cyanobacterium Microcystis flos-aquae to levofloxacin.
AB  - The effects of levofloxacin (LEV) on Microcystis flos-aquae and its mechanism
      were investigated by determining the responses of some parameters of M. flos
      aquae to LEV stress, including growth inhibition ratio, chlorophyll a content,
      superoxide dismutase (SOD) and catalase (CAT) activities, malondialdehyde (MDA)
      content, F v/F 0 and F v/F m, etc. The results indicated that LEV at 0.001-0.1
      MUg L(-1) could stimulate the growth of M. flos-aquae and increase the
      chlorophyll a content but did not induce a significant increase in the activity
      of antioxidant enzymes (SOD and CAT) and the content of MDA. When the LEV
      concentration exceeds 10 MUg L(-1), the growth of M. flos-aquae could be
      significantly inhibited (the highest inhibition ratio can be up to 88.38 % at 100
      MUg L(-1)) and chlorophyll a content, SOD and CAT activities, and MDA content
      also significantly decreased in a concentration-dependent manner, indicating that
      high concentrations of LEV caused a severe oxidative stress on algal cells,
      resulting in a large number of reactive oxygen species produced in algal cells
      and thereby inhibiting the growth of algae. At the same time, the F v/F m and F
      v/F 0 values of M. flos-aquae decreased significantly with both exposure time and
      increasing test concentration of LEV, showing that the process of photosynthesis
      was inhibited.

PMID- 24288062
TI  - Chromium exposure among children from an electronic waste recycling town of
      China.
AB  - Guiyu is one of the most heavily chromium-polluted areas in China due to the
      numerous informal electronic waste (e-waste) recycling activities. A 3-year
      (2004, 2006, and 2008) independent cross-sectional study on blood chromium (BCr)
      levels of 711 children from Guiyu and a control area was investigated.
      Questionnaire completed by parents/guardians was used to assess the risk factors
      of chromium (Cr) exposure, while physical examination, for the year 2008 only,
      was used to evaluate the effects of long-term exposure to Cr on child physical
      development. Children living in Guiyu had significantly higher BCr levels
      compared with those living in Chendian at the same period from 2004 to 2008 (P <
      0.001). The predominant risk factors related to elevated child BCr levels
      included the use of house as a family workshop, parent involved in e-waste
      recycling, and child residence in Guiyu. Children's weight and chest
      circumferences in group with high exposure to Cr (upper quartile) were higher
      than in the low-exposure group (P < 0.01), although the difference was less
      significant for boys between the two groups (P < 0.05). The results suggest that
      elevated child BCr in Guiyu due to informal e-waste recycling activities might be
      threatening the health of children, with implications on physical growth and
      development.

PMID- 24288063
TI  - Compaction stimulates denitrification in an urban park soil using 15N tracing
      technique.
AB  - Soils in urban areas are subjected to compaction with accelerating urbanization.
      The effects of anthropogenic compaction on urban soil denitrification are largely
      unknown. We conducted a study on an urban park soil to investigate how compaction
      impacts denitrification. By using (15)N labeling method and acetylene inhibition
      technique, we performed three coherent incubation experiments to quantify
      denitrification in compacted soil under both aerobic and anaerobic conditions.
      Uncompacted soil was set as the control treatment. When monitoring soil
      incubation without extra substrate, higher nitrous oxide (N2O) flux and
      denitrification enzyme activity were observed in the compacted soil than in the
      uncompacted soil. In aerobic incubation with the addition of K(15)NO3, N2O
      production in the compacted soil reached 10.11 ng N h(-1) g(-1) as compared to
      0.02 ng N h(-1) g(-1) in the uncompacted soil. Denitrification contributed 96 %
      of the emitted N2O in the compacted soil and 36 % of the emitted N2O in the
      uncompacted soil; total denitrification rate was higher in the compacted soil (up
      to 79.35 ng N h(-1) g(-1)) than in the uncompacted soil (0.11 ng N h(-1) g(-1)).
      Under anaerobic incubation with the addition of K(15)NO3, no statistical
      difference in total N losses and (15)N-(N2O+N2) flux between the uncompacted soil
      and the compacted soil was detected. Compaction promoted soil denitrification and
      may impact urban N biogeochemical cycling.

PMID- 24288064
TI  - Road traffic impact on urban water quality: a step towards integrated traffic,
      air and stormwater modelling.
AB  - Methods for simulating air pollution due to road traffic and the associated
      effects on stormwater runoff quality in an urban environment are examined with
      particular emphasis on the integration of the various simulation models into a
      consistent modelling chain. To that end, the models for traffic, pollutant
      emissions, atmospheric dispersion and deposition, and stormwater contamination
      are reviewed. The present study focuses on the implementation of a modelling
      chain for an actual urban case study, which is the contamination of water runoff
      by cadmium (Cd), lead (Pb), and zinc (Zn) in the Grigny urban catchment near
      Paris, France. First, traffic emissions are calculated with traffic inputs using
      the COPERT4 methodology. Next, the atmospheric dispersion of pollutants is
      simulated with the Polyphemus line source model and pollutant deposition fluxes
      in different subcatchment areas are calculated. Finally, the SWMM water quantity
      and quality model is used to estimate the concentrations of pollutants in
      stormwater runoff. The simulation results are compared to mass flow rates and
      concentrations of Cd, Pb and Zn measured at the catchment outlet. The
      contribution of local traffic to stormwater contamination is estimated to be
      significant for Pb and, to a lesser extent, for Zn and Cd; however, Pb is most
      likely overestimated due to outdated emissions factors. The results demonstrate
      the importance of treating distributed traffic emissions from major roadways
      explicitly since the impact of these sources on concentrations in the catchment
      outlet is underestimated when those traffic emissions are spatially averaged over
      the catchment area. 

PMID- 24288065
TI  - Human health risk assessment based on trace metals in suspended air particulates,
      surface dust, and floor dust from e-waste recycling workshops in Hong Kong,
      China.
AB  - This study investigated health risks exerted on electronic waste (e-waste)
      recycling workers exposed to cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb),
      nickel (Ni), mercury (Hg), and zinc (Zn) in Hong Kong. E-waste recycling
      workshops were classified into eight working areas: 1 = office, 2 = repair, 3 =
      dismantling, 4 = storage, 5 = desoldering, 6 = loading, 7 = cable shredding, and
      8 = chemical waste. The aforementioned metal concentrations were analyzed in
      suspended air particulates, surface dust and floor dust collected from the above
      study areas in five workshops. Elevated Pb levels were measured in dismantling
      and desoldering areas (582 and 486 MUg/100 cm(2) in surface and 3,610 and 19,172
      mg/kg in floor dust, respectively). Blood lead levels of 10 and 39.5 MUg/dl were
      estimated using United States Environmental Protection Agency's Adult Lead Model
      as a result of exposure to the floor dust from these two areas. Human health risk
      assessments were conducted to evaluate cancer and noncancer risks resulting from
      exposure to floor dust through the combined pathways of ingestion, dermal
      contact, and inhalation. Findings indicated that workers may be exposed to cancer
      risks above the acceptable range at 147 in a million at the 95th percentile in
      the dismantling area. Workers should be informed of associated risks to safeguard
      their health.

PMID- 24288066
TI  - Heavy metal contents in water, sediment and fish in a karst aquatic ecosystem of
      the Plitvice Lakes National Park (Croatia).
AB  - An evaluation of the quality status of the pristine karst, tufa depositing
      aquatic environment of the Plitvice Lakes National Park based on the analysis of
      heavy (ecotoxic) metals was examined for the first time. Analyses of trace metals
      in water, sediment and fish (Salmo trutta, Oncorhynchus mykiss, Squalius
      cephalus) samples were conducted either by stripping voltammetry (Zn, Cd, Pb and
      Cu) or cold vapour atomic absorption spectrometry (Hg). The concentration of
      dissolved trace metals in water was very low revealing a pristine aquatic
      environment (averages were, in ng/L: 258 (Zn), 10.9 (Cd), 11.7 (Pb), 115 (Cu) and
      1.22 (Hg)). Slightly enhanced concentrations of Cd (up to 50 ng/L) and Zn (up to
      900 ng/L) were found in two main water springs and are considered as of natural
      origin. Observed downstream decrease in concentration of Cd, Zn and Cu in both
      water and sediments is a consequence of the self-purification process governed by
      the formation and settling of authigenic calcite. Anthropogenic pressure was
      spotted only in the Kozjak Lake: Hg concentrations in sediments were found to be
      up to four times higher than the baseline value, while at two locations, Pb
      concentrations exceeded even a probable effect concentration. The increase of Hg
      and Pb was not reflected on their levels in the fish tissues; however,
      significant correlations were found between Cd level in fish tissues (liver and
      muscle) and in the water/sediment compartments, while only partial correlations
      were estimated for Zn and Cu. A high discrepancy between values of potentially
      bioavailable metal fraction estimated by different modelling programs/models
      raised the question about the usefulness of these data as a parameter in
      understanding/relating the metal uptake and their levels in aquatic organism. The
      aquatic environment of the Plitvice Lakes National Park is characterized, in
      general, as a clean ecosystem.

PMID- 24288067
TI  - Understanding the formation of colloidal mercury in acidic wastewater with high
      concentration of chloride ions by electrocapillary curves.
AB  - Acidic wastewater with high concentration of chloride ions was generated from
      washing elemental mercury (Hg(0)) existed in the roast flue gas by water. This
      process was simulated by mercury drops entering the electrolytes with its
      composition changed according to the characteristics of acidic wastewater.
      Electrocapillary curves of different electrolytes were determined by dropping
      mercury electrode to explore the formation mechanism of colloidal mercury in
      acidic wastewater. The changes of zeta (zeta) potentials were also obtained. The
      results indicate that chloride ions have a great impact on the formation of
      colloidal mercury. Thermodynamic calculation demonstrated that the main mercury
      species in acidic wastewater were HgCl2 (aq), HgCl3 (-), and HgCl4 (2-).
      Moreover, the model of colloidal mercury structure in acidic wastewater was
      established. Based on the changes of Gibbs free energy for ions passing through
      stern layer and metallic bond theory, it can be inferred that HgCl4 (2-) was
      preferentially over-adsorbed on the mercury interface by the weak pi chemical
      bond, and then positive charge ions such as heavy metal ions and H(+) were
      adsorbed due to the electrostatic force; thus, the colloidal mercury was formed.

PMID- 24288068
TI  - Arsenic removal from contaminated groundwater by membrane-integrated hybrid
      plant: optimization and control using Visual Basic platform.
AB  - A simulation software (ARRPA) has been developed in Microsoft Visual Basic
      platform for optimization and control of a novel membrane-integrated arsenic
      separation plant in the backdrop of absence of such software. The user-friendly,
      menu-driven software is based on a dynamic linearized mathematical model,
      developed for the hybrid treatment scheme. The model captures the chemical
      kinetics in the pre-treating chemical reactor and the separation and transport
      phenomena involved in nanofiltration. The software has been validated through
      extensive experimental investigations. The agreement between the outputs from
      computer simulation program and the experimental findings are excellent and
      consistent under varying operating conditions reflecting high degree of accuracy
      and reliability of the software. High values of the overall correlation
      coefficient (R (2) = 0.989) and Willmott d-index (0.989) are indicators of the
      capability of the software in analyzing performance of the plant. The software
      permits pre-analysis, manipulation of input data, helps in optimization and
      exhibits performance of an integrated plant visually on a graphical platform.
      Performance analysis of the whole system as well as the individual units is
      possible using the tool. The software first of its kind in its domain and in the
      well-known Microsoft Excel environment is likely to be very useful in successful
      design, optimization and operation of an advanced hybrid treatment plant for
      removal of arsenic from contaminated groundwater.

PMID- 24288069
TI  - The future of human-landscape interactions: drawing on the past, anticipating the
      future.

PMID- 24288070
TI  - High resolution mass spectrometry based techniques at the crossroads of metabolic
      pathways.
AB  - The metabolome is the set of small molecular mass compounds found in biological
      media, and metabolomics, which refers to as the analysis of metabolome in a given
      biological condition, deals with the large scale detection and quantification of
      metabolites in biological media. It is a data driven and multidisciplinary
      approach combining analytical chemistry for data acquisition, and biostatistics,
      informatics and biochemistry for mining and interpretation of these data. Since
      the middle of the 2000s, high resolution mass spectrometry is widely used in
      metabolomics, mainly because the detection and identification of metabolites are
      improved compared to low resolution instruments. As the field of HRMS is quickly
      and permanently evolving, the aim of this work is to review its use in different
      aspects of metabolomics, including data acquisition, metabolite annotation,
      identification and quantification. At last, we would like to show that, thanks to
      their versatility, HRMS instruments are the most appropriate to achieve optimal
      metabolome coverage, at the border of other omics fields such as lipidomics and
      glycomics.

PMID- 24288071
TI  - Relationships within aphids Cinara (Cupressobium) (Hemiptera) based on
      mitochondrial and nuclear DNA sequences.
AB  - The relationships between Cinara (Cupressobium) aphids inhabiting woody parts and
      leaves of conifers belonging to Cupressaceae have been studied using a
      mitochondrial gene (COI) and a nuclear gene (EF1-alpha). Based on the COI
      sequences, genetic distances between species ranged from 5.6 % between Cinara
      (C.) tujafilina (del Guercio) and Cinara (C.) juniperi (De Geer) to 10.5 %
      between C. (C.) tujafilina and Cinara (C.) mordvilkoi (Pasek). Genetic distances
      among EF1-alpha sequences were lower and showed from 0.1 % between C. cupressi
      and C. juniperi to 2.3 % between C. tujafilina and C. mordvilkoi. Molecular
      phylogenetic trees were constructed using the Bayesian inference (BI)
      phylogenetic analysis and maximum parsimony (MP) criterion. Phylogenetic trees
      obtained based on COI and EF1-alpha marker genes created two sister clades. Our
      results indicate that Cinara (Cupressobium) are a monophyletic group of aphids.
      Phylogenetic relationships amongst Cupressobium aphids do not result from the
      association with the host plant, but from the feeding site on the host plant or
      an ability to change the microhabitat on the plant. As closely related species
      inhabit similar microhabitats on different host plants, it suggests that the host
      switching is the main mode of speciation in this subgenus. 

PMID- 24288072
TI  - Composite interval mapping and mixed models reveal QTL associated with
      performance and carcass traits on chicken chromosomes 1, 3, and 4.
AB  - Interval mapping (IM) implemented in QTL Express or GridQTL is widely used, but
      presents some limitations, such as restriction to a fixed model, risk of mapping
      two QTL when there may be only one and no discrimination of two or more QTL using
      both cofactors located on the same and other chromosomes. These limitations were
      overcome with composite interval mapping (CIM). We reported QTL associated with
      performance and carcass traits on chicken chromosomes 1, 3, and 4 through
      implementation of CIM and analysis of phenotypic data using mixed models. Thirty
      four microsatellite markers were used to genotype 360 F2 chickens from crosses
      between males from a layer line and females from a broiler line. Sixteen QTL were
      mapped using CIM and 14 QTL with IM. Furthermore, of those 30 QTL, six were
      mapped only when CIM was used: for body weight at 35 days (first and third peaks
      on GGA4), body weight at 41 days (GGA1B and second peak on GGA4), and weights of
      back and legs (both on GGA4). Three new regions had evidence for QTL presence:
      one on GGA1B associated with feed intake 35-41 d at 404 cM (LEI0107-ADL0183) and
      two on GGA4 associated with weight of back at 163 cM (LEI0076-MCW0240) and weight
      gain 35-41 d, feed efficiency 35-41 d and weight of legs at 241 cM (LEI0085
      MCW0174). We dissected one more linked QTL on GGA4, where three QTL for BW35 and
      two QTL for BW41 were mapped. Therefore, these new regions mapped here need
      further investigations using high-density SNP to confirm these QTL and identify
      candidate genes associated with those traits. 

PMID- 24288074
TI  - Probing the neural basis of superstition.
AB  - Despite much evidence questioning its validity, superstitious belief continues to
      be rooted in the human mind. We used functional MRI to directly compare
      participants' neural responses to monetary attractiveness with their responses to
      the value of an auspicious date. We found that the right middle/superior frontal
      gyrus showed greater deactivation whenever an auspicious-based choice was made
      and that the contrast between the auspicious-based and economics-based choices
      was negatively correlated with the participants' rated wedding date-related
      superstitious belief, suggesting that a specific brain region carries decision
      signals which contribute to making decisions based on superstition and may be
      able to account for individual differences in superstitious behavior. The present
      investigation helps to reveal how the brain handles superstition. 

PMID- 24288075
TI  - Building synthetic cellular organization.
AB  - The elaborate spatial organization of cells enhances, restricts, and regulates
      protein-protein interactions. However, the biological significance of this
      organization has been difficult to study without ways of directly perturbing it.
      We highlight synthetic biology tools for engineering novel cellular organization,
      describing how they have been, and can be, used to advance cell biology. 

PMID- 24288076
TI  - A modified quadrant method for describing the femoral tunnel aperture positions
      in ACL reconstruction using two-view plain radiographs.
AB  - PURPOSE: A modified quadrant method was developed for description of femoral
      tunnel aperture positions on the sagittal plane after double-bundle anterior
      cruciate ligament (ACL) reconstruction, which can be measured by using two-view
      radiographs. The purpose of the study is to provide a new measurement method and
      to evaluate the reproducibility and accuracy of the method. METHODS: Forty-one
      patients who had undergone a double-bundle ACL reconstruction were investigated.
      Two-view plain radiographs, a 45-degree-flexion posterior-anterior standing
      (Rosenberg) and a lateral view, were taken at 1 year postoperatively, and the
      femoral tunnel positions were measured. Intra- and inter-observer reproducibility
      was calculated by means of intra-class correlation coefficient (ICC). Also, the
      accuracy of the method was evaluated by comparing the measurement from three
      dimensional computed tomography (3D-CT). RESULTS: Intra-observer reproducibility
      was excellent (ICC > 0.9). Inter-observer reproducibility of antero-medial (AM)
      tunnel position was almost perfect (ICC > 0.8) and that of postero-lateral (PL)
      tunnel was substantial (ICC > 0.7). The accuracy of the method was assessed by
      comparing the measurement from 3D-CT and was found to be almost perfect (ICC >
      0.8). With the modified quadrant method, the average height of AM and PL tunnels
      were 17.8 and 44.4 %, respectively, and the depth of AM and PL tunnels were 25.5
      and 36.7 %, respectively. CONCLUSIONS: A modified quadrant method was found to
      have acceptable reproducibility and accuracy. The method is useful for describing
      the femoral tunnel aperture positions in ACL reconstruction because of its
      easiness and simplicity. By using this method, it is possible to analyse the
      femoral tunnel position even in the cases without CT analysis. LEVEL OF EVIDENCE:
      IV.

PMID- 24288077
TI  - Less anterior knee pain with a routine lateral release in total knee arthroplasty
      without patellar resurfacing: a prospective, randomized study.
AB  - PURPOSE: Anterior knee pain is a major cause of complaint in total knee
      arthroplasty (TKA) without patellar resurfacing. The concept of improved patellar
      tracking and decreased retropatellar contact pressure for lateral retinacular
      release theoretically suggests that patients with lateral retinacular release in
      TKA would achieve a lower incidence of anterior knee pain when compared without
      lateral retinacular release. We sought to determine (1) whether those patients
      who received a routine lateral retinacular release in TKA would attain lower
      incidence of anterior knee pain as compared to patients who received TKA without
      lateral retinacular release and (2) whether lateral retinacular release would
      increase the lateral retinacular release-related complications. METHODS: A total
      of 148 patients who underwent TKA with the use of the Gemini MK II mobile bearing
      were randomized to receive either routine lateral retinacular release
      (intervention group) or not (control group). Patients were assessed by the visual
      analogue scale for anterior knee pain, the Knee Society clinical scoring system
      of knee score and function score, and patellar score for clinical function.
      Patients' satisfaction and lateral retinacular release-related complications were
      also evaluated. RESULTS: The overall incidence of anterior knee pain in the
      intervention group at 18 months follow-up was 5.6%, while that of the control
      group was 20.6% (p = 0.009). No statistical difference was detected between the
      two groups in terms of lateral retinacular release-related complications (n.s.),
      patients' satisfaction (n.s.), knee score (n.s.), function score (n.s.), and
      patellar score (n.s.) at 18 months follow-up. CONCLUSION: The present study
      suggests that routine lateral retinacular release can reduce anterior knee pain
      and does not increase lateral retinacular release-related complications, in TKA
      with the use of the Gemini MK II mobile bearing without patellar resurfacing.
      LEVEL OF EVIDENCE: Therapeutic, Level I.

PMID- 24288078
TI  - Prickles, latex, and tolerance in the endemic Hawaiian prickly poppy (Argemone
      glauca): variation between populations, across ontogeny, and in response to
      abiotic factors.
AB  - Covariance among plant defense traits is predicted to occur both within and among
      plant species, potentially leading to characteristic defense syndromes. I
      examined patterns of variation in prickle density, latex exudation, and tolerance
      in order to assess whether traits varied between populations, across plant
      ontogeny, and as phenotypic plasticity in response to water and light limitation
      and physical damage using the endemic Hawaiian prickly poppy, Argemone glauca, as
      a model system. Plants produced copious latex, had extremely variable prickle
      densities, and were generally tolerant of 50% defoliation. However, expression
      patterns differed among defense traits. Prickle density was consistent across
      ontogeny and was not induced by either water limitation or mechanical damage, but
      was significantly induced under high light conditions. In contrast, latex
      exudation increased significantly across ontogeny and was reduced by water
      limitation, but had no response to mechanical damage or light. Prickles, latex,
      and tolerance differed considerably between populations, suggesting different
      evolutionary histories for these populations. These disparate patterns indicate
      that latex and prickles are unlinked within A. glauca, potentially as a result of
      differences in their function, and providing little evidence that they jointly
      function as a defense syndrome. Moreover, this study provides the first
      description patterns of variation for multiple defense traits in an island
      endemic, and high levels of prickles, latex, and tolerance suggest that A. glauca
      is well defended against herbivores. Future research in the field will provide
      additional insights into the functional ecology of these traits in A. glauca.

PMID- 24288079
TI  - Innate threat-sensitive foraging: black-tailed deer remain more fearful of wolf
      than of the less dangerous black bear even after 100 years of wolf absence.
AB  - Anti-predator behaviors often entail foraging costs, and thus prey response to
      predator cues should be adjusted to the level of risk (threat-sensitive
      foraging). Simultaneously dangerous predators (with high hunting success) should
      engender the evolution of innate predator recognition and appropriate anti
      predator behaviors that are effective even upon the first encounter with the
      predator. The above leads to the prediction that prey might respond more strongly
      to cues of dangerous predators that are absent, than to cues of less dangerous
      predators that are actually present. In an applied context this would predict an
      immediate and stronger response of ungulates to the return of top predators such
      as wolves (Canis lupus) in many parts of Europe and North America than to
      current, less threatening, mesopredators. We investigated the existence of innate
      threat-sensitive foraging in black-tailed deer. We took advantage of a quasi
      experimental situation where deer had not experienced wolf predation for ca. 100
      years, and were only potentially exposed to black bears (Ursus americanus). We
      tested the response of deer to the urine of wolf (dangerous) and black bear (less
      dangerous). Our results support the hypothesis of innate threat-sensitive
      foraging with clear increased passive avoidance and olfactory investigation of
      cues from wolf, and surprisingly none to black bear. Prey which have previously
      evolved under high risk of predation by wolves may react strongly to the return
      of wolf cues in their environments thanks to innate responses retained during the
      period of predator absence, and this could be the source of far stronger non
      consumptive effects of the predator guild than currently observed.

PMID- 24288080
TI  - Overlap in nitrogen sources and redistribution of nitrogen between trees and
      grasses in a semi-arid savanna.
AB  - A key question in savanna ecology is how trees and grasses coexist under N
      limitation. We used N stable isotopes and N content to study N source
      partitioning across seasons from trees and associated grasses in a semi-arid
      savanna. We also used (15)N tracer additions to investigate possible
      redistribution of N by trees to grasses. Foliar stable N isotope ratio
      (delta(15)N) values were consistent with trees and grasses using mycorrhiza
      supplied N in all seasons except in the wet season when they switched to
      microbially fixed N. The dependence of trees and grasses on mineralized soil N
      seemed highly unlikely based on seasonal variation in mineralization rates in the
      Kruger Park region. Remarkably, foliar delta(15)N values were similar for all
      three tree species differing in the potential for N fixation through nodulation.
      The tracer experiment showed that N was redistributed by trees to understory
      grasses in all seasons. Our results suggest that the redistribution of N from
      trees to grasses and uptake of N was independent of water redistribution.
      Although there is overlap of N sources between trees and grasses, dependence on
      biological sources of N coupled with redistribution of subsoil N by trees may
      contribute to the coexistence of trees and grasses in semi-arid savannas. 

PMID- 24288082
TI  - Return to the operating room after resident-performed cataract surgery.

PMID- 24288083
TI  - Phototherapy effect on the muscular activity of regular physical activity
      practitioners.
AB  - Clinical investigations have demonstrated the effectiveness of phototherapy on
      the muscle activity. The aim of this study was to investigate the effect of low
      level laser therapy (LLLT) on the tibialis anterior muscle of regular physical
      activity practitioners by electromyographic, biomechanical, and biochemical
      (lactate) analysis. Double-blind controlled clinical trials were conducted with
      12 healthy females, regular physical activity practitioners, between 18 and 30
      years. The LLLT application (780 nm, 30 mW, 0.81 J/point, beam area of 0.2 cm(2),
      27 s, ~ 29 points) in the tibialis anterior muscle occurred after the
      delimitation of the points on every 4 cm(2) was held. It was observed that (a) a
      significant torque increase (p < 0.05) post-LLLT compared to the values after
      placebo therapy at the beginning of resistance exercise, (b) both muscle torque
      (isokinetic) and median frequency (EMG) showed a faster decay of the signals
      collected after placebo and laser treatment when compared to control values, (c)
      no significant change in torque in the strength test of five repetitions, (d) a
      significant muscle activity decrease (p < 0.05) after laser therapy compared to
      control values, and (e) an increase in lactate levels post-LLLT (p < 0.05) after
      30 min of exercise. It is concluded that the LLLT increased the muscle torque at
      the beginning of the exercise and maintained the levels of lactate after
      resistance exercise. Therefore, the LLLT with the parameters used in this study
      can be utilized in rehabilitation to improve muscle performance in elite
      athletes.

PMID- 24288084
TI  - TRPV1 Antagonists and Chronic Pain: Beyond Thermal Perception.
AB  - In the last decade, considerable evidence as accumulated to support the
      development of Transient Receptor Potential Vanilloid 1 (TRPV1) antagonists for
      the treatment of various chronic pain conditions. Whereas there is a widely
      accepted rationale for the development of TRPV1 antagonists for the treatment of
      various inflammatory pain conditions, their development for indications of
      chronic pain, where conditions of tactical, mechanical and spontaneous pain
      predominate, is less clear. Preclinical localization and expression studies
      provide a firm foundation for the use of molecules targeting TRPV1 for conditions
      of bone pain, osteoarthritis and neuropathic pain. Selective TRPV1 antagonists
      weakly attenuate tactile and mechanical hypersensivity and are partially
      effective for behavioral and electrophysiological endpoints that incorporate
      aspects of spontaneous pain. While initial studies with TRPV1 antagonist in
      normal human subjects indicate a loss of warm thermal perception, clinical
      studies assessing allelic variants suggests that TRPV1 may mediate other sensory
      modalities under certain conditions. The focus of this review is to summarize the
      current perspectives of TRPV1 for the treatment of conditions beyond those with a
      primary thermal sensitivity. 

PMID- 24288085
TI  - Genetic and Phenotypic Analyses of a Papaver somniferum T-DNA Insertional Mutant
      with Altered Alkaloid Composition.
AB  - The in vitro shoot culture of a T-DNA insertional mutant of Papaver somniferum L.
      established by the infection of Agrobacterium rhizogenes MAFF03-01724 accumulated
      thebaine instead of morphine as a major opium alkaloid. To develop a non-narcotic
      opium poppy and to gain insight into its genetic background, we have transplanted
      this mutant to soil, and analyzed its alkaloid content along with the manner of
      inheritance of T-DNA insertion loci among its selfed progenies. In the
      transplanted T0 primary mutant, the opium (latex) was found to be rich in
      thebaine (16.3% of dried opium) by HPLC analysis. The analyses on T-DNA insertion
      loci by inverse PCR, adaptor-ligation PCR, and quantitative real-time PCR
      revealed that as many as 18 copies of T-DNAs were integrated into a poppy genome
      in a highly complicated manner. The number of copies of T-DNAs was decreased to
      seven in the selected T3 progenies, in which the average thebaine content was 2.4
      fold that of the wild type plant. This may indicate that the high thebaine
      phenotype was increasingly stabilized as the number of T-DNA copies was
      decreased. In addition, by reverse transcription PCR analysis on selected
      morphine biosynthetic genes, the expression of codeine 6-O-demethylase was
      clearly shown to be diminished in the T0 in vitro shoot culture, which can be
      considered as one of the key factors of altered alkaloid composition. 

PMID- 24288086
TI  - Concerns regarding the use of dabigatran for stroke prevention in atrial
      fibrillation.
AB  - Dabigatran is an oral thrombin inhibitor which has been approved in several
      countries as an alternative to vitamin-K-antagonists for the prevention of stroke
      or embolism in atrial fibrillation patients. Dabigatran is introduced into
      clinical practice, although many issues regarding this drug are still unclear,
      like laboratory monitoring, use in elderly patients, drug- and food-interactions
      and use in patients with renal insufficiency. Additionally, there is no antidote
      for dabigatran. Thus, aim of the present review is to give an overview of
      concerns and unresolved issues concerning dabigatran. 

PMID- 24288087
TI  - Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6
      methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET.
AB  - Phosphodiesterase 10A (PDE10A) is a key enzyme of intracellular signal
      transduction which is involved in the regulation of neurotransmission. The
      molecular imaging of PDE10A by PET is expected to allow a better understanding of
      physiological and pathological processes related to PDE10A expression and
      function in the brain. The aim of this study was to develop a new 18F-labeled
      PDE10A ligand based on a 6,7-dimethoxy-4-pyrrolidinylquinazoline and to evaluate
      its properties in biodistribution studies. Nucleophilic substitution of the 7
      tosyloxy-analogue led to the 7-[18F]fluoroethoxy-derivative [18F]IV with
      radiochemical yields of 25% +/- 9% (n = 9), high radiochemical purity of >=99%
      and specific activities of 110-1,100 GBq/MUmol. [18F]IV showed moderate PDE10A
      affinity (KD,PDE10A = 14 nM) and high metabolic stability in the brain of female
      CD-1 mice, wherein the radioligand entered rapidly with a peak uptake of 2.3%
      ID/g in striatum at 5 min p.i. However, ex vivo autoradiographic and in vivo
      blocking studies revealed no target specific accumulation and demonstrated
      [18F]IV to be inapplicable for imaging PDE10A with PET. 

PMID- 24288088
TI  - Effects of Scrophularia ningpoensis Hemsl. on Inhibition of Proliferation,
      Apoptosis Induction and NF-kappaB Signaling of Immortalized and Cancer Cell
      Lines.
AB  - Scrophularia ningpoensis has been used in China for centuries as a herbal tea to
      treat various diseases. Based on the numerous animal studies on its
      pharmaceutical effects and the long time clinical experiences, we studied the
      molecular and cellular mechanism underlying the bioactivity of aqueous extract of
      Scrophularia and its isolated compounds. Seven isolated compounds, unlike
      Scrophularia extract, failed to induce cytotoxicity on HaCaT cells, but their
      combination improved the effect of extract. Tumor cell line selectivity was not
      observed, when we studied its cytotoxic effect on melanoma cell lines. The
      apoptotic and anti-inflammatory effects of Scrophularia extract have been
      demonstrated on HaCaT cells. The extract induced those effects potentially
      through affecting the MAPK pathway and inhibition of the NF-kappaB pathway,
      Microarray-based bioinformatical analyses on the compound acetoside from
      Scrophularia revealed a gene expression profile which confirmed our findings with
      the extract on proliferation inhibition, anti-inflammation and apoptosis. With
      DNA alkylation as major proposed mechanism of action, we assume acetoside as one
      of the active compounds in Scrophularia. 

PMID- 24288090
TI  - Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA
      Microcapsules for Oral Delivery: Preparation and in Vitro Characterization.
AB  - Probiotics possess potential therapeutic and preventative effects for various
      diseases and metabolic disorders. One important limitation for the oral delivery
      of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT)
      which challenge bacterial viability and activity. One proposed method to surpass
      this obstacle is the use of microencapsulation to improve the delivery of
      bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L
      lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB
      5221 and characterize its enzymatic activity and viability through a simulated
      GIT. This specific strain, in previous research, was characterized for its
      inherent ferulic acid esterase (FAE) activity which could prove beneficial in the
      development of a therapeutic for the treatment and prevention of cancers and
      metabolic disorders. Our findings demonstrate that the APA microcapsule does not
      slow the mass transfer of substrate into and that of the FA product out of the
      microcapsule, while also not impairing bacterial cell viability. The use of
      simulated gastrointestinal conditions led to a significant 2.5 log difference in
      viability between the free (1.10 * 104 +/- 1.00 * 103 cfu/mL) and the
      microencapsulated (5.50 * 106 +/- 1.00 * 105 cfu/mL) L. fermentum NCIMB 5221
      following exposure. The work presented here suggests that APA microencapsulation
      can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a
      FAE-active probiotic strain. 

PMID- 24288091
TI  - Discrepant thyroid function test results in a 44-year-old man.

PMID- 24288092
TI  - Commentary.

PMID- 24288089
TI  - Structure based antibody-like peptidomimetics.
AB  - Biologics such as monoclonal antibodies (mAb) and soluble receptors represent new
      classes of therapeutic agents for treatment of several diseases. High affinity
      and high specificity biologics can be utilized for variety of clinical purposes.
      Monoclonal antibodies have been used as diagnostic agents when coupled with
      radionuclide, immune modulatory agents or in the treatment of cancers. Among
      other limitations of using large molecules for therapy the actual cost of
      biologics has become an issue. There is an effort among chemists and biologists
      to reduce the size of biologics which includes monoclonal antibodies and
      receptors without a reduction of biological efficacy. Single chain antibody,
      camel antibodies, Fv fragments are examples of this type of deconstructive
      process. Small high-affinity peptides have been identified using phage screening.
      Our laboratory used a structure-based approach to develop small-size
      peptidomimetics from the three-dimensional structure of proteins with
      immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived
      either from the receptor or their cognate ligand mimics the functions of the
      parental macromolecule. These constrained peptides not only provide a platform
      for developing small molecule drugs, but also provide insight into the atomic
      features of protein-protein interactions. A general overview of the reduction of
      monoclonal antibodies to small exocyclic peptide and its prospects as a useful
      diagnostic and as a drug in the treatment of cancer are discussed. 

PMID- 24288093
TI  - Commentary.

PMID- 24288094
TI  - An elderly man with a calcified brain.

PMID- 24288098
TI  - Synthesis of porous, hollow metal MCO(3) (M=Mn, Co, Ca) microstructures and
      adsorption properties thereof.
AB  - Porous, hollow metal carbonate microstructures show many unique properties, and
      are attractive for various applications. Herein, we report the first
      demonstration of a general strategy to synthesize hollow metal carbonate
      structures, including porous MnCO3 hollow cubics, porous CoCO3 hollow rhombuses
      and porous CaCO3 hollow capsules. For example, the porous, hollow MnCO3
      microcubes show larger Brunauer-Emmett-Teller (BET) surface areas of 359.5 m(2) 
      g(-1) , which is much larger than that of solid MnCO3 microcubics (i.e., 12.03
      m(2)  g(-1) ). As a proof of concept, these porous MnCO3 hollow microcubes were
      applied to water treatment and exhibited an excellent ability to remove organic
      pollutants in waste water owing to their hollow structure and large specific
      surface area. 

PMID- 24288099
TI  - Hemorrhage in cerebral fat embolisms in a cat model using triolein dependent on
      the physical properties of triolein.
AB  - PURPOSE: Hemorrhage is a finding of clinical fat embolism syndrome. The purpose
      of the present study was to evaluate the occurrence of hemorrhage in the cat
      brain by SW MR imaging after infusion of triolein as a bolus or as an emulsion
      into the carotid artery. MATERIALS AND METHODS: Twenty-two cats were divided into
      two groups according to the type of triolein infused: group 1 (n = 11) was
      infused with a 0.1 ml triolein bolus, group 2 (n = 11) with triolein emulsion
      containing 0.1 ml triolein in 20 ml saline. SW imaging was performed before and
      after triolein infusion (at 2 h, 1 and 4 days). After MR imaging on day 4, cats
      were sacrificed and brains were immediately excised. Hemorrhage was evaluated
      using H&E staining. RESULTS: Hemorrhage was observed in eight cats in group 1, in
      no cats in group 2. Hemorrhage on SW images was found to correspond with light
      microscopy. CONCLUSIONS: SW images revealed hemorrhage in lesion hemispheres
      infused with triolein bolus. However, there was no evidence of hemorrhage infused
      with emulsified triolein. Thus, the occurrence of hemorrhage in cerebral fat
      embolism may depend on fat status.

PMID- 24288100
TI  - Ectomesenchymal chondromyxoid tumour of the posterior tongue.
AB  - Ectomesenchymal chondromyxoid tumor (ECMT) is a rare benign neoplasm arising in
      the tongue. With only 45 cases reported in the literature, there are several
      unique features defining this lesion. Firstly, almost all patients present with
      an asymptomatic slow growing mass on the anterior dorsum of the tongue. At the
      microscopic level, it is recognizable as a well-circumscribed unencapsulated
      proliferation of uniform round to fusiform cells embedded in a chondromyxoid
      matrix. Lastly, the immunohistochemistry profile is characterised by positivity
      for glial fibrillary acidic protein and frequent positivity for S-100 and
      cytokeratins. We report a case of a mass located on the posterior dorsum of the
      tongue and meeting the aforementioned morphological and immunohistochemical
      criteria of ECMT. 

PMID- 24288101
TI  - [Personality traits in patients with migraine: a multi-centre study using the
      Salamanca screening questionnaire].
AB  - INTRODUCTION: Psychiatric comorbidity is frequent in cases of migraine and
      research has focused more on that related to affective disorders and anxiety than
      to personality traits. AIMS: To study the presence of personality traits in
      persons with migraine and how they are related with the presence of chronic
      migraine or medication abuse. PATIENTS AND METHODS: Patients attended
      consecutively in five centres were evaluated. The 22 questions in the Salamanca
      screening questionnaire were used to explore 11 personality traits classified in
      three groups. Data were obtained concerning demographic characteristics and the
      impact of migraine. RESULTS: The sample used in the study included 164 patients
      (134 females and 30 males), with a mean age of 36.6 +/- 12.5 years (range: 18-78
      years). In most patients, the impact of migraine was high. The personality traits
      that appeared most frequently were: anxious (53.7%), anankastic (44.5%),
      histrionic (40.9%) and dependent (32.9%). The risk of chronic migraine was higher
      in patients with the anankastic trait (relative risk = 2.06; confidence interval
      at 95% = 1.07-3.94; p = 0.027). CONCLUSIONS: Some of the personality traits that
      can be detected with the Salamanca questionnaire are very common in patients with
      migraine. In our series, the anankastic trait is related with the presence of
      chronic migraine.

PMID- 24288102
TI  - [Effects of combined aerobic and resistance training on cognition following
      stroke: a systematic review].
AB  - INTRODUCTION: Stroke is one of the main causes of disability. Physical activity
      has shown a benefit in the physical rehabilitation of these patients. However,
      its role improving cognitive function has not been studied by far. AIM: To review
      studies that evaluate the impact of physical activity on cognitive recovery after
      stroke. PATIENTS AND METHODS: We searched in CENTRAL, Medline and ISI Web of
      Knowledge, for studies that analyzed the effect of a physical intervention (both
      aerobic or resistance exercise) on cognition following stroke. RESULTS: Five
      studies were identified (93 patients). Studies show a wide heterogeneity in the
      tests used for cognitive assessment and also in exercise protocols. Identified
      studies support a positive impact of aerobic exercise on cognition. The two
      latest published studies (50 patients) have specifically evaluated the impact of
      combined aerobic and resistance training on cognition. The results suggest that
      the addition of resistance training may improve overall cognitive function and
      particularly executive function. CONCLUSIONS: Physical activity constitutes a
      promising strategy to improve cognitive function following stroke. Larger
      clinical trials and homogeneity in both exercise protocols and cognitive
      assessment instruments are needed.

PMID- 24288103
TI  - [Frontal variant of Alzheimer's disease. Two pathologically confirmed cases and a
      literature review].
AB  - INTRODUCTION: Alzheimer's disease (AD) is the most frequent degenerative dementia
      in our setting. In most patients the initial manifestations of the disease
      consist in a selective and progressive compromise of memory. Yet, it is not a
      homogeneous process and in some cases the mode of presentation can be atypical.
      The presentation of AD in the form of an early disorder affecting personality,
      behaviour and the executive functions has been called the frontal variant of AD.
      In our case, its definitive diagnosis was only possible by means of a
      histological analysis, given the fact that the applicable clinical criteria were
      then insufficient to reach a diagnosis of this atypical form of AD. CASE REPORTS:
      We report the cases of two patients, one female and one male aged 60 and 52
      respectively, who presented a progressive picture of cognitive impairment with
      initial involvement of the executive functions and personality changes, together
      with mood disorders. As a result, the initial diagnosis was one of probable
      frontotemporal dementia. However, in both cases, the autopsy revealed data
      consistent with a diagnosis of AD, with a distribution of the pathology that
      essentially affected the frontal lobes. CONCLUSIONS: AD has a heterogeneous form
      of presentation, which can give rise to errors in its initial diagnosis, since
      current clinical criteria do not take this clinical variability sufficiently into
      account. We therefore consider it important to pay attention to the atypical
      forms of AD with the aim of developing new diagnostic methods that allow AD to be
      distinguished from other degenerative processes.

PMID- 24288104
TI  - [Rizatriptan: experience after 15 years of clinical use].
AB  - We review the development of rizatriptan, one of the seven 5-HT1B/1D agonists
      available for the symptomatic treatment of migraine, emphasizing the most
      relevant contributions carried out from our country. Rizatriptan has shown the
      quickest onset of action, both in controlled studies and in the different
      metaanalyses, which translates in high efficacy levels at two hours. Its
      tolerability and safety profile is similar to that of the other compounds in this
      pharmacological group. Postlaunching studies have shown that its high efficacy
      leads to pharmacoeconomic savings and to a robust preference and satisfaction by
      the patient for this triptan. Its efficacy is improved with an early use within
      migraine attacks and recent data have shown also efficacy in adolescents. This
      global profile places rizatriptan as a triptan of first choice for any kind of
      migraine attacks. 

PMID- 24288105
TI  - [Genetic, environmental, and epigenetic contribution to the susceptibility to
      autism spectrum disorders].
AB  - INTRODUCTION: Autism spectrum disorders (ASD) are common and complex
      neuropsychiatric disorders in which multiple factors may contribute to the
      phenotype. AIM: To review current knowledge about possible risk factors for ASD.
      DEVELOPMENT: Medline, OMIM and Ensembl databases were searched for possible risk
      factors, disease and gene information. CONCLUSIONS: There is genetic
      heterogeneity and probably different modes of transmission in ASD. In addition,
      many cases are related with non-inherited de novo mutations or uncommon alleles
      with a large effect. The general heritability in these disorders may be lower
      than previously reported. Some fraction of it may be explained by relatively
      common alleles that tend to have a small effect. To some extent, susceptibility
      alleles may have a different influence on the phenotype depending on other
      genetic or non-genetic factors. Non-genetic factors in the perinatal and
      postnatal period, including epigenetics, the age of the father and possibly the
      age of grandparents at conception may be relevant for ASD. The mechanisms
      involved in the etiology of ASD may be related with synaptic development and
      connectivity, neurotransmission, signaling, neuroplasticity, and gene expression.
      Different methods have contributed to understand the etiology of ASD. Linkage and
      association studies are not appropriate for ASD cases with de novo mutations with
      a strong effect. The observed increase in ASD prevalence may be related not only
      with more awareness, changing diagnostic criteria, and environmental exposures,
      but also with epigenetic changes, and an increasing number of de novo mutations.

PMID- 24288107
TI  - [Juvenile Alpers disease].

PMID- 24288108
TI  - [Facts, values, duties... and neurons].

PMID- 24288109
TI  - Intravascular large B cell lymphoma presenting as cholecystitis: diagnostic
      challenges persist.

PMID- 24288110
TI  - Relapsing bloodstream infections during treatment of acute leukemia.
AB  - Acute leukemia (AL) patients may experience more than one episode of bloodstream
      infection (BSI) caused by the same pathogen during the entire chemotherapy
      program. In order to identify factors influencing BSI recurrence (R-BSI) during
      subsequent phases of treatment, we analyzed all BSIs occurring to consecutively
      treated AL patients during a period of active epidemiologic surveillance at our
      institution between 2004 and 2011. Two hundred and fifty BSIs were observed in
      138 patients receiving more than 1 cycle of chemotherapy. BSI due to the same
      pathogen recurred in 39/138 (28.3 %) patients. Gram-negative rods (GNRs)
      accounted for 59.6 % and Gram-positive cocci (GPCs) for 34.4 % of BSI. Four
      pathogens were involved in R-BSI: Escherichia coli, Pseudomonas aeruginosa,
      coagulase-negative staphylococci, and Streptococcus viridans. GNRs were
      significantly more frequent among R-BSI compared to non-relapsing BSI (nR-BSI)
      [69/94 (73.4 %) vs 70/156 (50.6 %), p < 0.0001]; in particular, E. coli accounted
      for 67 % of R-BSI vs 32.1 % of nR-BSI (p < 0.0001). Receiving more than four
      chemotherapy courses and having an extended spectrum beta-lactamase (ESBL)
      producing E. coli BSI at any time of treatment were significantly associated to R
      BSI. A trend toward a higher mortality among R-BSI patients in comparison with nR
      BSI was observed (17.9 and 7.1 %, respectively, p = 0.12). Among AL patients, R
      BSI is a frequent phenomenon, which may contribute to the shift of epidemiology
      toward GNR and to a higher mortality. This should significantly impact the
      strategies of antibiotic prophylaxis and treatment in patients with AL. 

PMID- 24288112
TI  - Entropy-driven lectin-recognition of multivalent glycovesicles.
AB  - Multivalent glycovesicle recognition over lectin layers emphasizes effects on the
      dynamic lateral fluidity of glycoside clusters upon multivalent binding at the
      bilayer surface and vice versa. 

PMID- 24288113
TI  - Double network bacterial cellulose hydrogel to build a biology-device interface.
AB  - Establishing a biology-device interface might enable the interaction between
      microelectronics and biotechnology. In this study, electroactive hydrogels have
      been produced using bacterial cellulose (BC) and conducting polymer (CP)
      deposited on the BC hydrogel surface to cover the BC fibers. The structures of
      these composites thus have double networks, one of which is a layer of
      electroactive hydrogels combined with BC and CP. The electroconductivity provides
      the composites with capabilities for voltage and current response, and the BC
      hydrogel layer provides good biocompatibility, biodegradability, bioadhesion and
      mass transport properties. Such a system might allow selective biological
      functions such as molecular recognition and specific catalysis and also for
      probing the detailed genetic and molecular mechanisms of life. A BC-CP composite
      hydrogel could then lead to a biology-device interface. Cyclic voltammetry and
      electrochemical impedance spectroscopy (EIS) are used here to study the composite
      hydrogels' electroactive property. BC-PAni and BC-PPy respond to voltage changes.
      This provides a mechanism to amplify electrochemical signals for analysis or
      detection. BC hydrogels were found to be able to support the growth, spreading
      and migration of human normal skin fibroblasts without causing any cytotoxic
      effect on the cells in the cell culture. These double network BC-CP hydrogels are
      biphasic Janus hydrogels which integrate electroactivity with biocompatibility,
      and might provide a biology-device interface to produce implantable devices for
      personalized and regenerative medicine. 

PMID- 24288114
TI  - Weight and urinary incontinence: the missing links.
AB  - Excessive weight is an established and potent risk factor for urinary
      incontinence (UI) among women of all ages. Although few would doubt that weight
      plays a role in UI, there are still many uncertainties regarding weight as a risk
      factor. It must be clarified whether body mass index (BMI) is a better estimate
      than weight, waist circumference, or waist-hip ratio. It is not clear how the
      distribution of weight affects UI. Does being overweight due to heavy muscles,
      edema, or pregnancy lead to UI or only being overweight due to adiposity? It is
      unclear for how long a person's overweight must persist to lead to UI. We do not
      know whether weight is an appropriate measure of exposure or whether the
      association between weight and UI is confounded by socioeconomic status, diet,
      disease, or weight-related hormonal changes. This article summarizes knowledge
      gaps on the association between weight and UI. 

PMID- 24288111
TI  - The pathogenic relevance of the prognostic markers CD38 and CD49d in chronic
      lymphocytic leukemia.
AB  - The interactions of chronic lymphocytic leukemia cells with the microenvironment
      in secondary lymphoid tissues and the bone marrow are known to promote CLL cell
      survival and proliferation. CD38 and CD49d are both independent prognostic risk
      parameters in CLL with important roles in shaping these interactions. Both are
      reported to influence CLL cell trafficking between blood and lymphoid organs as
      well as their survival and proliferation within the lymphoid organs, thereby
      impacting the pathophysiology of the disease. The expression of CD38 and CD49d is
      associated in the majority of cases, and they exist as part of macromolecular
      complexes. Here, we review the current evidence for the individual and associated
      contributions of these molecules to CLL pathophysiology. 

PMID- 24288115
TI  - Transurethral incision of the bladder neck improves voiding efficiency in female
      patients with detrusor underactivity.
AB  - INTRODUCTION AND HYPOTHESIS: Detrusor underactivity (DU) is a common urologic
      problem and usually presents with urine retention or large postvoid residual
      (PVR). Medical treatment of DU does not always achieve satisfactory results. We
      report the surgical outcomes of transurethral incision of the bladder neck (TUI
      BN) in women with DU and urine retention. METHODS: A total 31 woman with DU in
      whom medical treatment failed underwent TUI-BN and were retrospectively studied.
      Surgical outcome was determined by postoperative urodynamic studies and clinical
      presentation. Patients with postoperative voiding efficiency of >67% had
      excellent outcomes, those with 33-66% had moderate results, and those with <33%
      had poor surgical outcomes. RESULT: PVR, voiding efficiency, and maximum urinary
      flow rate (Qmax) significantly improved after TUI-BN. PVR decreased by 56.3%
      overall. Intermittent catheterization was needed in 27 patients before surgery
      and in only seven after TUI-BN. There were 14 (45.2%), 11 (35.5%), and six
      (19.3%) patients with excellent, moderate, and poor surgical outcomes,
      respectively. Baseline urodynamic parameters, age, and etiologies did not impact
      surgical outcome. Three patients developed transient urinary incontinence, and
      one developed vesicovaginal fistula after TUI-BN. CONCLUSION: TUI-BN is an
      effective procedure to improve PVR, Qmax, and voiding efficiency in women with DU
      and urine retention. The procedure is safe and effective, even in patients with
      medical treatment failure, those with large PVR at baseline, and those with
      different etiologies.

PMID- 24288116
TI  - Human ortholog of a plant salicylic acid receptor found in SK-N-SH cell line.
AB  - Our previous studies have described the purification and characterization of a
      novel plant NAD(P)-reductase like protein (RL) from the thermogenic appendix of
      the Sauromatum guttatum inflorescence. RL is mainly located in cytoplasm of
      thermogenic plants and it can act like a bistable switch. It adopts a compact
      conformation during heat-production and a more expanded conformation when heat is
      not generated. Addition of salicylic acid, a natural thermogenic inducer, at
      picomolar concentration to a solution of purified RL induced a discontinuous
      volume phase transition in which the volume of RL in the oligomeric form expanded
      and shrunk repeatedly every 4-5 min. In the present study using ESI-MS analysis
      we have demonstrated the existence of RL in the human SK-N-SH cell line and in
      mouse brain tissue. The molecular mass of human RL is in the same range as of its
      plant counterpart, 34,140 +/- 34 Da. The charge state distribution of the human
      RL is identical to its plant counterpart from the Sauromatum appendix during heat
      production. Human RL was present in the compact state when it was purified from
      the SK-N-SH cell line When these cells were treated with salicylic acid (10 MUM)
      a shift to a much more compact conformation was observed. It seems that the
      potential of RL to respond to salicylic acid was conserved. These results may
      reveal the existence of a thermoregulation system that is evolutionarily
      conserved and is operating by conformational changes. This discovery may also
      represent an opportunity for a better understanding of some of the diverse
      functions of salicylic acid and aspirin in plants and humans. 

PMID- 24288117
TI  - Physico-chemical characterization and biological response of Labeo rohita-derived
      hydroxyapatite scaffold.
AB  - The chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite
      (HAp) biomaterials. Thermogravimetric and differential thermal analyses of fish
      scale materials reveal the different phase changes with temperature and find out
      the suitable calcination temperatures. The composition and structures of wet ball
      milled calcined HAp powders are characterized by Fourier transform infrared
      spectroscopy, X-ray diffraction, field emission scanning electron microscopy,
      transmission electron microscopy, energy dispersive X-ray analysis (EDX). The EDX
      as well as chemical analysis of fish scale-derived apatite materials confirms
      that the Ca/P ratio is 1.71. The compressive stress, hardness and porosity have
      been evaluated on sintered HAp biomaterials. The cell attachment on HAp surfaces,
      cytotoxicity evaluation and MTT assay, which are carried out in RAW macrophage
      like cell line media demonstrate good biocompatibility. The histological analysis
      also supports the bioaffinity of processed HAp biomaterials in Wistar rat model
      for investigating the contact reaction and stability at the artificial or natural
      prosthesis interface. 

PMID- 24288118
TI  - Probing the intracellular glutathione redox potential by in-cell NMR
      spectroscopy.
AB  - Non-invasive and real-time analysis of cellular redox processes has been greatly
      hampered by lack of suitable measurement techniques. Here we describe an in-cell
      nuclear magnetic resonance (NMR) based method for measuring the intracellular
      glutathione redox potential by direct and quantitative measurement of
      isotopically labeled glutathione introduced exogenously into living yeast. By
      using this approach, perturbations in the cellular glutathione redox homeostasis
      were also monitored as yeast cells were subjected to oxidative stress. 

PMID- 24288119
TI  - Toxic effect in the lungs of rats after inhalation exposure to benzalkonium
      chloride.
AB  - BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC)
      toxic to microorganisms. Inhalation is one of the major possible routes of human
      exposure to BAC. MATERIALS AND METHODS: Experiments were performed on female
      Wistar rats. The rats were exposed to aerosol of BAC water solution at the target
      concentration of 0 (control group) and 35 mg/m(3) for 5 days (6 h/day) and, after
      a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the
      target concentration of 0 (control group) and 35 mg/m3 for 6 h. RESULTS: Compared
      to the controls, the animals exposed to BAC aerosol were characterized by lower
      food intake and their body weight was significantly smaller. As regards BAC
      exposed group, a significant increase was noted in relative lung mass, total
      protein concentration, and MIP-2 in BALF both directly after the termination of
      the exposure and 18 h afterwards. Significantly higher IL-6 and IgE
      concentrations in BALF and a decrease in the CC16 concentration in BALF were
      found in the exposed group immediately after the exposure. The leukocyte count in
      BALF was significantly higher in the animals exposed to BAC aerosol compared to
      the controls. In the lungs of rats exposed to BAC the following effects were
      observed: minimal perivascular, interstitial edema, focal aggregates of alveolar
      macrophages, interstitial mononuclear cell infiltrations, thickened alveolar
      septa and marginal lipoproteinosis. CONCLUSION: Inhalation of BAC induced a
      strong inflammatory response and a damage to the blood-air barrier. Reduced
      concentrations of CC16, which is an immunosuppressive and anti-inflammatory
      protein, in combination with increased IgE concentrations in BALF may be
      indicative of the immuno-inflammatory response in the animals exposed to BAC
      aerosol by inhalation. Histopathological examinations of tissue samples from the
      BAC-exposed rats revealed a number of pathological changes found only in the
      lungs.

PMID- 24288120
TI  - Adeno-associated virus-mediated expression of recombinant CBD-HepII polypeptide
      of human fibronectin inhibits metastasis of breast cancer.
AB  - CH50, a recombinant CBD-HepII polypeptide of human fibronectin, was shown to
      suppress tumor metastasis in murine hepatocarcinoma and melanoma models. However,
      the effect of CH50 on human cancer cells is still not clear. Here we evaluated
      the efficiency of CH50 delivered by recombinant adeno-associated virus (rAAV)
      vector for breast cancer treatment. Infection of the two human breast cancer cell
      line MDA-MB-231 and MDA-MB-468 with a rAAV2 vector encoding CH50 resulted in
      secretion of soluble CH50. In vitro rAAV-CH50 transduction inhibited adhesion to
      ECM molecules, and transwell migration and invasion of breast cancer cells
      induced by fibronectin. In both breast cancer cells, rAAV-CH50 targeted
      alphaVbeta3 signaling, namely inhibited the expression of alphaVbeta3, the
      activation of FAK, the upregulation of cdc2, and the production and activation of
      MMP-9 by ECM molecules stimulation. rAAV-mediated tail vein transfusion and
      stable expression of CH50 in the liver resulted in the long-term presence of CH50
      in sera of nude mice. Sustained CH50 expression mediated by rAAV vector
      suppressed the growth and spontaneous metastasis of orthotopic breast cancer
      xenograft, experimental metastasis of circulating breast cancer cells, and
      improved the long-term survival of breast tumor-bearing mice. These findings
      suggest for the first time that rAAV-CH50 gene therapy may present a novel and
      promising strategy for treatment against metastatic breast cancer. 

PMID- 24288122
TI  - Prognostic role of microRNA polymorphisms in patients with advanced esophageal
      squamous cell carcinoma receiving platinum-based chemotherapy.
AB  - PURPOSE: MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and
      prognosis. The aim of this study was to evaluate the effects of miRNA
      polymorphisms on clinical outcomes in patients with advanced esophageal squamous
      cell carcinoma (ESCC) treated with platinum-based chemotherapy. METHODS: Five
      polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR
      125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with
      advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes
      and drug response, toxicity, and overall survival were analyzed. RESULTS: miR
      146a rs2910164 was significantly associated with an increased risk of severe
      hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171
      0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a
      rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 %
      CI 1.112-2.165, P = 0.010; HR = 2.171, 95 % CI 1.173-4.017, P = 0.014,
      respectively]. Combined analysis revealed a 4.073-fold increased risk of death in
      patients carrying two unfavorable genotypes (P = 0.002). CONCLUSIONS: Taken
      together, these findings indicate that miRNA polymorphisms may predict prognosis
      in advanced ESCC patients receiving platinum-based chemotherapy.

PMID- 24288121
TI  - E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and
      irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung
      cancer.
AB  - PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by
      topoisomerase 2 inhibitors was assessed in a randomized phase II study in
      extensive-stage small-cell lung cancer (SCLC). METHODS: Patients with previously
      untreated extensive-stage SCLC with measurable disease, ECOG performance status
      of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan
      (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20
      mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of
      irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by
      etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle. RESULTS:
      We enrolled 140 patients and randomized 66 eligible patients to each arm. Only
      54.5 % of all patients completed the planned maximum 6 cycles. There were grade
      >=3 treatment-related adverse events in approximately 70 % of the patients on
      both arms including 6 treatment-related grade 5 events. The overall response
      rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A
      and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median
      progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5
      months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 %
      CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B.
      CONCLUSION: Sequential administration of topoisomerase inhibitors did not improve
      on the historical efficacy of standard platinum-doublet chemotherapy for
      extensive-stage SCLC.

PMID- 24288124
TI  - Recovering hidden quanta of Cu(2+)-doped ZnS quantum dots in reductive
      environment.
AB  - We report that photoluminescence of doped quantum dots (Qdots)-which was
      otherwise lost in the oxidized form of the dopant-could be recovered in chemical
      or cellular reducing environment. For example, as-synthesized Cu(2+)-doped zinc
      sulfide (ZnS) Qdots in water medium showed weak emission with a peak at 420 nm,
      following excitation with UV light (320 nm). However, addition of reducing agent
      led to the appearance of green emission with a peak at 540 nm and with quantum
      yield as high as 10%, in addition to the weak peak now appearing as a shoulder.
      The emission disappeared in the presence of an oxidizing agent or with time under
      ambient conditions. X-Ray photoelectron spectroscopic (XPS) and electron spin
      resonance (ESR) measurements suggested the presence of Cu(2+) in the as
      synthesized Qdots, while formation of its reduced form was indicated (by ESR
      results) following treatment with a reducing agent. Transmission electron
      microscopy (TEM) and X-ray diffraction (XRD) studies confirmed the formation of
      ZnS nanocrystals, the size and shape of which did not undergo any change in the
      presence of a reducing or oxidizing agent. Nanoparticulate forms of the Qdots and
      chitosan (a biopolymer) composite exhibited similar emission characteristics.
      Interestingly, when mammalian cancer cells or non-cancerous cells were treated
      with the composite nanoparticles (NPs), characteristic green fluorescence was
      observed. Further, the intensity of the fluorescence diminished when the cells
      were treated later with pyrogallol-a known reactive oxygen species generator.
      Overall, the results indicated a new way of probing the reducing nature of
      mammalian cells using the emission properties of the Qdot based on the redox
      state of its dopant. 

PMID- 24288123
TI  - New whole-body multimodality imaging of gastric cancer peritoneal metastasis
      combining fluorescence imaging with ICG-labeled antibody and MRI in mice.
AB  - BACKGROUND: Peritoneal metastasis is the most frequent pattern of recurrence
      after curative surgery for gastric cancer. However, such a recurrence is
      difficult to detect by conventional computed tomography (CT) and magnetic
      resonance imaging (MRI) at an early stage. To improve the sensitivity and
      specificity of diagnostic imaging for peritoneal metastasis, we developed a new
      type of multimodality imaging combining fluorescence imaging with near-infrared
      fluorophore (NIR)-labeled antibodies and MRI. METHODS: Dual optical imaging of
      peritoneal metastasis was carried out using luciferase-tagged gastric cancer cell
      lines and XenoLight CF750 or indocyanine green (ICG)-labeled anti-human epidermal
      growth factor receptor (EGFR) or CEA antibody as a probe in mice with Ivis in
      vivo imaging system. RESULTS: This whole-body fluorescent imaging system
      sensitively detected metastatic foci <1 mm in diameter in the peritoneal cavity
      noninvasively. Fluorescence imaging proved to be specific because the
      fluorescence signal was abolished by blocking with excess unlabeled antibody.
      Although this fluorescence imaging had higher sensitivity for detection of small
      sized peritoneal metastases than MRI, it proved difficult to accurately determine
      organ distribution of the metastasis. We thus developed a multimodality imaging
      system by the fusion of the three-dimensional fluorescence image with the MRI
      image and demonstrated its improved diagnostic accuracy over either method alone.
      CONCLUSION: The present results suggest that multimodality imaging consisting of
      fluorescence imaging with NIR-labeled EGFR or CEA antibody and MRI allows
      sensitive, specific, and anatomically accurate detection of peritoneal metastasis
      noninvasively at an early stage.

PMID- 24288125
TI  - Female second-year undergraduate medical students' attitudes towards research at
      the College of Medicine, Alfaisal University: a Saudi Arabian perspective.
AB  - There is a rapidly increasing movement towards integrating scientific research
      training into undergraduate medical education. The aim of this study was to
      explore the perceived attitudes of female second-year undergraduate medical
      students towards research at the College of Medicine, Alfaisal University, Saudi
      Arabia, as well as to explore if any differences exist between students with and
      without previous research experiences. An online, anonymous, cross-sectional,
      self-rating survey was administered. A two-tailed Mann-Whitney U test was used to
      compare the mean 5-point Likert scale responses between students with and without
      previous research experiences. Sixty-one students (61/81) participated in the
      survey with a 75.3 % response rate. Nineteen participants (31.1 %) had previous
      research experiences. Overall, all students demonstrated positive attitudes
      towards undergraduate research. There were significant statistical differences in
      the means of attitudes towards undergraduate research between students with
      versus without previous research experiences in regards to the following
      statements: 'my adequate possession of research knowledge and skills promotes
      participation in future research activities' (3.4 vs. 2.9; p < 0.02), 'I will
      participate in scientific research activities throughout my undergraduate medical
      education' (3.7 vs. 3.1; p < 0.00), and 'I have no interest at all in scientific
      research' (1.6 vs. 2.4; p < 0.01). Previous exposure to scientific research
      experiences promotes more positive attitudes towards scientific research. 

PMID- 24288126
TI  - Students as teachers: the value of peer-led teaching.

PMID- 24288127
TI  - The effect of a daily quiz (TOPday) on self-confidence, enthusiasm, and test
      results for biomechanics.
AB  - Many students in Biomedical Sciences have difficulty understanding biomechanics.
      In a second-year course, biomechanics is taught in the first week and examined at
      the end of the fourth week. Knowledge is retained longer if the subject material
      is repeated. However, how does one encourage students to repeat the subject
      matter? For this study, we developed 'two opportunities to practice per day
      (TOPday)', consisting of multiple-choice questions on biomechanics with immediate
      feedback, which were sent via e-mail. We investigated the effect of TOPday on
      self-confidence, enthusiasm, and test results for biomechanics. All second-year
      students (n = 95) received a TOPday of biomechanics on every regular course day
      with increasing difficulty during the course. At the end of the course, a non
      anonymous questionnaire was conducted. The students were asked how many TOPday
      questions they completed (0-6 questions [group A]; 7-18 questions [group B]; 19
      24 questions [group C]). Other questions included the appreciation for TOPday,
      and increase (no/yes) in self-confidence and enthusiasm for biomechanics. Seventy
      eight students participated in the examination and completed the questionnaire.
      The appreciation for TOPday in group A (n = 14), B (n = 23) and C (n = 41) was
      7.0 (95 % CI 6.5-7.5), 7.4 (95 % CI 7.0-7.8), and 7.9 (95 % CI 7.6-8.1),
      respectively (p < 0.01 between A and C). Of the students who actively
      participated (B and C), 91 and 80 % reported an increase in their self-confidence
      and enthusiasm, respectively, for biomechanics due to TOPday. In addition, they
      had a higher test result for biomechanics (p < 0.01) compared with those who did
      not actively participate (A). In conclusion, the teaching method 'TOPday' seems
      an effective way to encourage students to repeat the subject material, with the
      extra advantage that students are stimulated to keep on practising for the
      examination. The appreciation was high and there was a positive association
      between active participation, on the one hand, and self-confidence, enthusiasm,
      and test results for biomechanics on the other. 

PMID- 24288128
TI  - Re-evaluation of the predictive score for 6-month graft survival in living donor
      liver transplantation in the modern era.
AB  - The limitations of donor age, graft size, and the Model for End-Stage Liver
      Disease (MELD) score have not been apparent in living donor liver transplantation
      (LDLT). Our team developed a formula for predicting graft survival after LDLT;
      the formula includes the graft weight, donor age, MELD score, and portosystemic
      shunt status. The aims of this study were to re-evaluate the reliability of our
      formula and to assess whether our modified treatment strategy has improved 6
      month graft survival. Two hundred seventeen patients were allocated into 2
      groups: patients with predictive scores >= 1.30 (n = 162) and patients with
      predictive scores < 1.30 (n = 55). The latter group was also divided into
      subgroups of patients with scores of 1.15 to 1.30 (n = 37) and patients with
      scores < 1.15 (n = 18). Survival rates for patients with scores < 1.30 were
      significantly worse than rates for patients with scores >= 1.30 (P = 0.006).
      Survival rates for patients with scores < 1.15 were significantly worse than
      rates for patients with scores of 1.15 to <1.30 (P < 0.001). A multivariate
      analysis showed that a predictive score < 1.15 (odds ratio = 7.87, P = 0.006) and
      a body mass index >= 30 kg/m(2) (odds ratio = 13.3, P < 0.001) were independent
      risk factors for 6-month graft mortality. In conclusion, predictive scores
      reliably predict 6-month graft survival and could allow a widening of the safe
      ranges for donor ages and graft sizes.

PMID- 24288129
TI  - Curcumin promotes exosomes/microvesicles secretion that attenuates lysosomal
      cholesterol traffic impairment.
AB  - SCOPE: Exosomes/microvesicles are originated from multivesicular bodies that
      allow the secretion of endolysosome components out of the cell. In the present
      work, we investigated the effects of curcumin, a polyphenol, on
      exosomes/microvesicles secretion in different cells lines, using U18666A as a
      model of intracellular cholesterol trafficking impairment. METHODS AND RESULTS:
      In both HepG2 hepatocarcinoma cells and THP-1 differentiated macrophages,
      treatment with curcumin affected the size and the localization of
      endosome/lysosomes accumulated by U18666A, and reduced the cholesterol cell
      content. To ascertain the mechanism, we analyzed the incubation medium. Curcumin
      stimulated the release of cholesterol and the lysosomal beta-hexosaminidase
      enzyme, as well as the exosome markers, flotillin-2 and CD63. Electron microscopy
      studies demonstrated the presence of small vesicles similar to
      exosomes/microvesicles in the secretion fluid. These vesicles harbored CD63 on
      their surface, indicative of their endolysosomal origin. These effects of
      curcumin were particularly intense in cells treated with U18666A. CONCLUSION:
      These findings indicate that curcumin ameliorates the U18666A-induced
      endolysosomal cholesterol accumulation by shuttling cholesterol and presumably
      other lipids out of the cell via exosomes/microvesicles secretion. This action
      may contribute to the potential of curcumin in the treatment of lysosomal storage
      diseases.

PMID- 24288130
TI  - Identification and distribution of rRNH1, a gene upregulated after spinal cord
      primary neuron injury.
AB  - Our previous study identified and characterized one differentially expressed
      gene, Rattus norvegicus ribonuclease/angiogenin inhibitor 1 (rRNH1).
      Transcriptional activity of lots of genes involves in spinal cord injury (SCI)
      and regeneration, but the mechanisms remain unknown. In the present study, we
      analyzed the sequences of rRNH1 and examined the expression pattern of rRNH1 in
      different adult rat tissues. We found the sequences of rRNH1 show high homology
      to Homo sapiens ribonuclease/angiogenin inhibitor 1; it encoded a protein of 461
      amino acid residues and contained 13 leucine-rich repeat motifs. Using real-time
      quantitative PCR (q-PCR), rRNH1 mRNA was widely expressed in adult rat tissues,
      especially in the central nervous system. Moreover, rRNH1 protein was found to be
      upregulated after SCI. Although the precise function of rRNH1 is unknown, its
      unique expression pattern and upregulation after SCI suggest that rRNH1 might be
      involved in the succeeding injury and/or regeneration processes of injured spinal
      cord. All these data make rRNH1 a new interesting start to study the mechanisms
      of SCI and neuron regeneration. 

PMID- 24288131
TI  - Peroxisome proliferator-activated receptor gamma regulates genes involved in
      insulin/insulin-like growth factor signaling and lipid metabolism during
      adipogenesis through functionally distinct enhancer classes.
AB  - The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is a
      transcription factor whose expression is induced during adipogenesis and that is
      required for the acquisition and control of mature adipocyte functions. Indeed,
      PPAR induces the expression of genes involved in lipid synthesis and storage
      through enhancers activated during adipocyte differentiation. Here, we show that
      PPAR also binds to enhancers already active in preadipocytes as evidenced by an
      active chromatin state including lower DNA methylation levels despite higher CpG
      content. These constitutive enhancers are linked to genes involved in the
      insulin/insulin-like growth factor signaling pathway that are transcriptionally
      induced during adipogenesis but to a lower extent than lipid metabolism genes,
      because of stronger basal expression levels in preadipocytes. This is consistent
      with the sequential involvement of hormonal sensitivity and lipid handling during
      adipocyte maturation and correlates with the chromatin structure dynamics at
      constitutive and activated enhancers. Interestingly, constitutive enhancers are
      evolutionary conserved and can be activated in other tissues, in contrast to
      enhancers controlling lipid handling genes whose activation is more restricted to
      adipocytes. Thus, PPAR utilizes both broadly active and cell type-specific
      enhancers to modulate the dynamic range of activation of genes involved in the
      adipogenic process.

PMID- 24288132
TI  - Novel mechanism of positive versus negative regulation by thyroid hormone
      receptor beta1 (TRbeta1) identified by genome-wide profiling of binding sites in
      mouse liver.
AB  - Triiodothyronine (T3) regulates key metabolic processes in the liver through the
      thyroid hormone receptor, TRbeta1. However, the number of known target genes
      directly regulated by TRbeta1 is limited, and the mechanisms by which positive
      and especially negative transcriptional regulation occur are not well understood.
      To characterize the TRbeta1 cistrome in vivo, we expressed a biotinylated TRbeta1
      in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRbeta1
      targets, and correlated these data with gene expression changes. As with other
      nuclear receptors, the majority of TRbeta1 binding sites were not in proximal
      promoters but in the gene body of known genes. Remarkably, T3 can dictate changes
      in TRbeta1 binding, with strong correlation to T3-induced gene expression
      changes, suggesting that differential TRbeta1 binding regulates transcriptional
      outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at
      binding sites where T3 induced an increase or decrease in TRbeta1 binding,
      respectively, leading to either positive or negative regulation by T3. Taken
      together, the results of this study provide new insights into the mechanisms of
      transcriptional regulation by TRbeta1 in vivo. 

PMID- 24288134
TI  - Dopamine and Cu+/2+ can induce oligomerization of alpha-synuclein in the absence
      of oxygen: Two types of oligomerization mechanisms for alpha-synuclein and
      related cell toxicity studies.
AB  - alpha-Synuclein oligomers can induce neurotoxicity and are implicated in
      Parkinson's disease etiology and disease progression. Many studies have reported
      alpha-synuclein oligomerization by dopamine (DA) and transition metal ions, but
      few studies provide insight into joint influences of DA and Cu2+ . In this study,
      DA and Cu2+ were coadministered aerobically to measure alpha-synuclein
      oligomerization under these conditions. In the presence of oxygen, DA induced
      alpha-synuclein oligomerization in a dose-dependent manner. Cu+/2+ did not effect
      oligomerization in such a manner in the presence of DA. By electrophoresis, Cu2+
      was found easily to induce oligomerization with DA. This implies that
      oligomerization invoked by DA is reversible in the presence of Cu2+, which
      appears to be mediated by noncovalent bond interactions. In the absence of
      oxygen, DA induced less oligomerization of alpha-synuclein, whereas DA/Cu2+
      induced aerobic-level amounts of oligomers, suggesting that DA/Cu2+ induces
      oligomerization independent of oxygen concentration. Radical species were
      detected through electron paramagnetic resonance (EPR) spectroscopic analysis
      arising from coincubation of DA/Cu2+ with alpha-synuclein. Redox reactions
      induced by DA/Cu2+ were observed in multimer regions of alpha-synuclein oligomers
      through NBT assay. Cellular toxicity results confirm that, for normal and hypoxic
      conditions, copper or DA/Cu2+ can induce cell death, which may arise from copper
      redox chemistry. From these results, we propose that DA and DA/Cu2+ induce
      different mechanisms of alpha-synuclein oligomerization, cross-linking with
      noncovalent (or reversible covalent) bonding vs. likely radical-mediated covalent
      modification.

PMID- 24288133
TI  - Anterior-posterior regionalized gene expression in the Ciona notochord.
AB  - BACKGROUND: In the simple ascidian chordate Ciona, the signaling pathways and
      gene regulatory networks giving rise to initial notochord induction are largely
      understood and the mechanisms of notochord morphogenesis are being systematically
      elucidated. The notochord has generally been thought of as a non
      compartmentalized or regionalized organ that is not finely patterned at the level
      of gene expression. Quantitative imaging methods have recently shown, however,
      that notochord cell size, shape, and behavior vary consistently along the
      anterior-posterior (AP) axis. RESULTS: Here we screen candidate genes by whole
      mount in situ hybridization for potential AP asymmetry. We identify 4 genes that
      show non-uniform expression in the notochord. Ezrin/radixin/moesin (ERM) is
      expressed more strongly in the secondary notochord lineage than the primary. CTGF
      is expressed stochastically in a subset of notochord cells. A novel calmodulin
      like gene (BCamL) is expressed more strongly at both the anterior and posterior
      tips of the notochord. A TGF-beta ortholog is expressed in a gradient from
      posterior to anterior. The asymmetries in ERM, BCamL, and TGF-beta expression are
      evident even before the notochord cells have intercalated into a single-file
      column. CONCLUSIONS: We conclude that the Ciona notochord is not a homogeneous
      tissue but instead shows distinct patterns of regionalized gene expression.

PMID- 24288135
TI  - Serum ferritin and nutritional status: insights from an eating disorders clinic
      population.
AB  - OBJECTIVE: To determine the relationship between serum ferritin and malnutrition
      in newly assessed patients at a paediatric eating disorders clinic. DESIGN: This
      was a prospectively assessed clinical cohort study. SETTING: Intake assessment
      clinic of a tertiary eating disorders service for children and adolescents.
      METHODS: Clinical, anthropometric and laboratory features of children and
      adolescents were systematically measured. The relationship of serum ferritin to
      other clinical, anthropometric and laboratory measures was determined using
      linear regression. RESULTS: A total of 121 female patients aged 9.5-17.6 years
      were included, with body mass index (BMI) z score -5.7 to 1.9 (median -1.3).
      Using multiple regression, serum ferritin was inversely associated with BMI z
      score (regression coefficient (beta)=-0.234, 95% CI -0.413 to -0.055) and serum
      insulin-like growth factor 1 (IGF-1) (beta=-0.476, 95% CI -0.884 to -0.068) and
      positively associated with alanine aminotransferase (beta=0.357, 95% CI 0.055 to
      0.659, controlling for age, pubertal stage and serum iron). CONCLUSIONS: In
      malnourished adolescents with eating disorders increased serum ferritin is
      associated with lower BMI z score and serum IGF-1.

PMID- 24288136
TI  - Persistent neck pain in a girl: Klippel-Feil syndrome.

PMID- 24288137
TI  - Group B streptococci in milk and neonatal colonisation.

PMID- 24288138
TI  - Self-assembled selenium monolayers: from nanotechnology to materials science and
      adaptive catalysis.
AB  - Self-assembled monolayers (SAMs) of selenium have emerged into a rapidly
      developing field of nanotechnology with several promising opportunities in
      materials chemistry and catalysis. Comparison between sulfur-based self-assembled
      monolayers and newly developed selenium-based monolayers reveal outstanding
      complimentary features on surface chemistry and highlighted the key role of the
      headgroup element. Diverse structural properties and reactivity of organosulfur
      and organoselenium groups on the surface provide flexible frameworks to create
      new generations of materials and adaptive catalysts with unprecedented
      selectivity. Important practical utility of adaptive catalytic systems deals with
      development of sustainable technologies and industrial processes based on natural
      resources. Independent development of nanotechnology, materials science and
      catalysis has led to the discovery of common fundamental principles of the
      surface chemistry of chalcogen compounds. 

PMID- 24288139
TI  - Confinement has no effect on visual space perception: The results of the Mars-500
      experiment.
AB  - People confined to a closed space live in a visual environment that differs from
      a natural open-space environment in several respects. The view is restricted to
      no more than a few meters, and nearby objects cannot be perceived relative to the
      position of a horizon. Thus, one might expect to find changes in visual space
      perception as a consequence of the prolonged experience of confinement. The
      subjects in our experimental study were participants of the Mars-500 project and
      spent nearly a year and a half isolated from the outside world during a simulated
      mission to Mars. The participants were presented with a battery of computer-based
      psychophysical tests examining their performance on various 3-D perception tasks,
      and we monitored changes in their perceptual performance throughout their
      confinement. Contrary to our expectations, no serious effect of the confinement
      on the crewmembers' 3-D perception was observed in any experiment. Several
      interpretations of these findings are discussed, including the possibilities that
      (1) the crewmembers' 3-D perception really did not change significantly, (2)
      changes in 3-D perception were manifested in the precision rather than the
      accuracy of perceptual judgments, and/or (3) the experimental conditions and the
      group sample were problematic.

PMID- 24288141
TI  - Flow of suspensions of carbon nanotubes carrying phase change materials through
      microchannels and heat transfer enhancement.
AB  - This work explores the potential of nano-encapsulated phase change materials
      (PCMs) in applications related to microelectronics cooling. PCMs (wax or meso
      erythritol) were encapsulated in carbon nanotubes (CNTs) by a method of self
      sustained diffusion at room temperature and pressure. These nano-encapsulated wax
      nanoparticles alone allowed heat removal over a relatively wide range of
      temperatures (different waxes have melting temperatures in the range 40-80 
      degrees C). On the other hand, nano-encapsulated meso-erythritol nanoparticles
      allowed heat removal in the range 118-120  degrees C. The combination of these
      two PCMs (wax and meso-erythritol) could extend the temperature range to 40-120 
      degrees C, when both types of nanoparticles (wax and meso-erythritol
      intercalated) would be suspended in the same carrier fluid (an oil). The
      nanoparticles possess a short response time of the order of 10(-7) s. Such nano
      encapsulation can also prevent the PCM from sticking to the wall. In this work,
      experiments with wax-intercalated CNTs, stable aqueous suspensions of CNTs with
      concentrations up to 3 wt% with and without nano-encapsulated wax were prepared
      using a surfactant sodium dodecyl benzene sulfonate (NaDDBS). These suspensions
      were pumped through two channels of 603 MUm or 1803 MUm in diameter subjected to
      a constant heat flux at the wall. It was found that the presence of the
      surfactant in CNT suspensions results in a pseudo-slip at the channel wall which
      enhances the flow rate at a fixed pressure drop. When aqueous solutions of the
      surfactant were employed (with no CNTs added), the enhanced convection alone was
      responsible for a ~2  degrees C reduction in temperature in comparison with pure
      water flows. When CNTs with nano-encapsulated wax were added, an additional ~1.90
      degrees C reduction in temperature due to the PCM fusion was observed when using
      3 wt% CNT suspensions. In addition, suspensions of meso-erythritol-intercalated
      CNTs in alpha-olefin oil were used as coolants in flows through the 1803 MUm
      diameter microchannel. These suspensions (1.5 wt% CNT) revealed a temperature
      reduction due to the PCM fusion of up to 3.2  degrees C, and a fusion temperature
      in the range 118-120  degrees C. 

PMID- 24288140
TI  - A CTD-Pfizer collaboration: manual curation of 88,000 scientific articles text
      mined for drug-disease and drug-phenotype interactions.
AB  - Improving the prediction of chemical toxicity is a goal common to both
      environmental health research and pharmaceutical drug development. To improve
      safety detection assays, it is critical to have a reference set of molecules with
      well-defined toxicity annotations for training and validation purposes. Here, we
      describe a collaboration between safety researchers at Pfizer and the research
      team at the Comparative Toxicogenomics Database (CTD) to text mine and manually
      review a collection of 88,629 articles relating over 1,200 pharmaceutical drugs
      to their potential involvement in cardiovascular, neurological, renal and hepatic
      toxicity. In 1 year, CTD biocurators curated 254,173 toxicogenomic interactions
      (152,173 chemical-disease, 58,572 chemical-gene, 5,345 gene-disease and 38,083
      phenotype interactions). All chemical-gene-disease interactions are fully
      integrated with public CTD, and phenotype interactions can be downloaded. We
      describe Pfizer's text-mining process to collate the articles, and CTD's curation
      strategy, performance metrics, enhanced data content and new module to curate
      phenotype information. As well, we show how data integration can connect
      phenotypes to diseases. This curation can be leveraged for information about
      toxic endpoints important to drug safety and help develop testable hypotheses for
      drug-disease events. The availability of these detailed, contextualized, high
      quality annotations curated from seven decades' worth of the scientific
      literature should help facilitate new mechanistic screening assays for
      pharmaceutical compound survival. This unique partnership demonstrates the
      importance of resource sharing and collaboration between public and private
      entities and underscores the complementary needs of the environmental health
      science and pharmaceutical communities. Database URL: http://ctdbase.org/

PMID- 24288142
TI  - A microgel construction kit for bioorthogonal encapsulation and pH-controlled
      release of living cells.
AB  - pH-Cleavable cell-laden microgels with excellent long-term viabilities were
      fabricated by combining bioorthogonal strain-promoted azide-alkyne cycloaddition
      (SPAAC) and droplet-based microfluidics. Poly(ethylene glycol)dicyclooctyne and
      dendritic poly(glycerol azide) served as bioinert hydrogel precursors. Azide
      conjugation was performed using different substituted acid-labile benzacetal
      linkers that allowed precise control of the microgel degradation kinetics in the
      interesting pH range between 4.5 and 7.4. By this means, a pH-controlled release
      of the encapsulated cells was achieved upon demand with no effect on cell
      viability and spreading. As a result, the microgel particles can be used for
      temporary cell encapsulation, allowing the cells to be studied and manipulated
      during the encapsulation and then be isolated and harvested by decomposition of
      the microgel scaffolds. 

PMID- 24288143
TI  - Mandibulofacial dysostosis (Treacher-Collins syndrome) in the fetus: novel
      association with Pectus carinatum in a molecularly confirmed case and review of
      the fetal phenotype.
AB  - BACKGROUND: Treacher Collins syndrome is the most common mandibulofacial
      dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected
      fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case
      of perinatal death or pregnancy termination. METHODS: We describe the
      ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected
      fetus, and review the clinical, prenatal, and postmortem findings in 15
      previously reported fetal and perinatal cases. RESULTS: A nearly complete
      spectrum of the typical facial characteristics can be present by the early second
      trimester of gestation, including subtle defects such as lower eyelid colobomas.
      Mandibular hypoplasia and bilateral auricle defects were constant findings in the
      affected fetal population. Downslanting palpebral fissures were the second more
      common feature, followed by midface hypoplasia, polyhydramnios, and ocular
      defects. Association with Pierre Robin sequence was common (38%) in the reviewed
      series. Previously unreported pectus carinatum was noted in our case bearing a
      heterozygous TCOF1 mutation. Other unique reported findings include salivary
      gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all
      in molecularly unconfirmed cases. CONCLUSION: Treacher Collins syndrome can be
      prenatally detected by ultrasound and should be included in the wide range of
      genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses
      tend to have a more severe phenotype than living patients. The reported
      association of Treacher Collins syndrome type 1 with pectus carinatum expands the
      phenotype, provides information on genotype-phenotype correlation, and suggests
      possible pathogenetic interactions between neural crest cell disorders and the
      formation of the sternum that merit investigation.

PMID- 24288145
TI  - Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).
AB  - BACKGROUND: There has been renewal of interest in the use of prophylactic
      antibiotics to reduce the frequency of exacerbations and improve quality of life
      in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether
      or not regular treatment of COPD patients with prophylactic antibiotics reduces
      exacerbations or affects quality of life. SEARCH METHODS: We searched the
      Cochrane Airways Group Trials Register and bibliographies of relevant studies.
      The latest literature search was August 2013. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) that compared prophylactic antibiotics with placebo in
      patients with COPD. DATA COLLECTION AND ANALYSIS: We used the standard methods of
      The Cochrane Collaboration. Data were extracted and analysed by two independent
      review authors. MAIN RESULTS: Seven RCTs involving 3170 patients were included in
      this systematic review. All studies were published between 2001 and 2011. Five
      studies were of continuous antibiotics and two studies were of intermittent
      antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics
      investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin.
      Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin
      is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study
      duration varied from three months to 36 months and all used intention-to-treat
      analysis. Most of the results were of moderate quality. The risk of bias of the
      included studies was generally low, and we did not downgrade the quality of
      evidence for risk of bias.The trials recruited participants with a mean age of 66
      years and with at least a moderate severity of COPD. Three trials included
      participants with frequent exacerbations and two trials recruited participants
      requiring systemic steroids or antibiotics, or both, or who were at the end stage
      of their disease and required oxygen.The primary outcomes for this review were
      the number of exacerbations and quality of life.With use of continuous
      prophylactic antibiotics the number of patients experiencing an exacerbation was
      reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3
      studies, 1262 participants, high quality). This represented a reduction from 69%
      of participants in the control group compared to 54% in the treatment group (95%
      CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb)
      was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced
      with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58
      to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in
      the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study,
      1149 participants, moderate quality) and the test for interaction showed that
      this result was significantly different from the effect on exacerbations with
      continuous antibiotics.There was a statistically significant improvement in
      quality of life with both continuous and pulsed antibiotic treatment but this was
      smaller than the four unit improvement that is regarded as being clinically
      significant (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants,
      moderate quality).Neither pulsed nor continuous antibiotics showed a significant
      effect on the secondary outcomes of frequency of hospital admissions, change in
      lung function, serious adverse events or all-cause mortality (moderate quality
      evidence).The adverse events that were recorded varied among the trials depending
      on the different antibiotics used. Azithromycin was associated with a significant
      hearing loss in the treatment group. The moxifloxacin pulsed study reported a
      significantly higher number of adverse events in the treatment arm due to the
      marked increase in gastrointestinal adverse events (P < 0.001). Some adverse
      events that led to drug discontinuation, such as development of long QTc or
      tinnitus, were not significantly more frequent in the treatment group than the
      placebo group but pose important considerations in clinical practice.The
      development of antibiotic resistance in the community is of major concern. One
      study found newly colonised patients to have higher rates of antibiotic
      resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at
      initiation of therapy rapidly became resistant with the quinolone treatment.
      AUTHORS' CONCLUSIONS: Use of continuous prophylactic antibiotics results in a
      clinically significant benefit in reducing exacerbations in COPD patients. All
      trials of continuous antibiotics used macrolides hence the noted benefit applies
      only to the use of continuous macrolide antibiotics. The impact of pulsed
      antibiotics remains uncertain and requires further research.The trials in this
      review included patients who were frequent exacerbators and needed treatment with
      antibiotics or systemic steroids, or who were on supplemental oxygen. There were
      also older individuals with a mean age of 66 years. The results of these trials
      apply only to the group of patients who were studied in these trials and may not
      be generalisable to other groups.Because of concerns about antibiotic resistance
      and specific adverse effects, consideration of prophylactic antibiotic use should
      be mindful of the balance between benefits to individual patients and the
      potential harms to society created by antibiotic overuse.

PMID- 24288146
TI  - [In Process Citation].

PMID- 24288144
TI  - Maternal caffeine consumption and small for gestational age births: results from
      a population-based case-control study.
AB  - Caffeine is consumed in various forms during pregnancy, has increased half-life
      during pregnancy and crosses the placental barrier. Small for gestational age
      (SGA) is an important perinatal outcome and has been associated with long term
      complications. We examined the association between maternal caffeine intake and
      SGA using National Birth Defects Prevention Study data. Non-malformed live born
      infants with an estimated date of delivery from 1997-2007 (n = 7,943) were
      included in this analysis. Maternal caffeine exposure was examined as total
      caffeine intake and individual caffeinated beverage type (coffee, tea, and soda);
      sex-, race/ethnic-, and parity-specific growth curves were constructed to
      estimate SGA births. Crude and adjusted odds ratios (aORs) and 95% confidence
      intervals were estimated using unconditional logistic regression. Interaction
      with caffeine exposures was assessed for maternal smoking, vasoconstrictor
      medication use, and folic acid. Six hundred forty-eight infants (8.2%) were found
      to be SGA in this analysis. Increasing aORs were observed for increasing intakes
      of total caffeine and for each caffeinated beverage with aORs (adjusting for
      maternal education, high blood pressure, and smoking) ranging from 1.3 to 2.1 for
      the highest intake categories (300+ mg/day total caffeine and 3+ servings/day for
      each beverage type). Little indication of additive interaction by maternal
      smoking, vasoconstrictor medication use, or folic acid intake was observed. We
      observed an increase in SGA births for mothers with higher caffeine intake,
      particularly for those consuming 300+ mg of caffeine per day. Increased aORs were
      also observed for tea intake but were more attenuated for coffee and soda intake.

PMID- 24288147
TI  - Prevention and surgical management of postburn contractures of the hand.
AB  - In addition to burn surgeons, skilled nurses, and therapists, hand surgeons are a
      key part of the multidisciplinary team caring for patients following thermal
      injury to the hand. Despite appropriate initial treatment and compressive
      therapy, contractures are common after deep burn. The most common and
      functionally limiting are web space and hand contractures. Web space contractures
      can be managed with excision followed by local soft tissue rearrangement or skin
      grafting. The classic burn claw hand deformity includes extension contracture of
      the metacarpophalangeal joints and flexion contractures of the proximal
      interphalangeal joints. The mainstay of management of these postburn contractures
      includes complete surgical release of scar tissue and replacement by full
      thickness skin graft. In cases in which scar contracture release results in major
      exposure of the tendons or joints, distant tissue transfer is required. This
      review focuses on prevention and management of late sequelae of thermal injury to
      the hand focusing on contractures of the webspaces and hand. 

PMID- 24288148
TI  - An intelligent nanotheranostic agent for targeting, redox-responsive ultrasound
      imaging, and imaging-guided high-intensity focused ultrasound synergistic
      therapy.
AB  - A novel multifunctional nanotheranostic agent with targeting, redox-responsive
      ultrasound imaging and ultrasound imaging-guided high-intensity focused
      ultrasound (HIFU) therapy (MSNC-PEG-HA(SS)-PFH, abbreviated as MPH(SS)-PFH)
      capabilities is developed. The redox-responsive guest molecule release and
      ultrasound imaging functions can be both integrated in such a "smart" theranostic
      agent, which is accomplished by the redox-triggered transition from the
      crosslinking state to retrocrosslinking state of the grafted polyethylene glycol
      disulfide hyaluronic acid molecules on the particle surface when reaching a
      reducing environment in vitro. More importantly, under the tailored ultrasound
      imaging guiding, in vivo Hela tumor-bearing nude mice can be thoroughly and
      spatial-accurately ablated during HIFU therapy, due to the targeted accumulation,
      responsive ultrasound imaging guidance and the synergistic ablation functions of
      nanotheranostic agent MPH(SS)-PFH in the tumors. This novel multifunctional nano
      platform can serve as a promising candidate for further studies on oncology
      therapy, due to its high stability, responsive and indicative ultrasound imaging
      of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under
      ultrasound-guidance.

PMID- 24288149
TI  - Cardiovascular ATIP (Angiotensin receptor type 2 interacting protein) expression
      in mouse development.
AB  - BACKGROUND: ATIPs (Angiotensin receptor type 2 [AT2] interacting proteins) are
      described as AT2 interacting protein variants, whereas their expression and
      functions during development are not known yet. RESULTS: Here, we provide a
      detailed expression pattern of ATIP variants during mouse development by
      visualizing Mtus1 promotor activity, Mtus1 RNA, and subsequent ATIP protein
      expression. ATIPs are strongly expressed in the developing cardiovascular system,
      including the vascular plexus of the yolk sac and the fetal vascular part of the
      placenta. Moreover, ATIP is expressed spatially distinct during eye and limb bud
      development, and in later stages in lung and nervous system. The three murine
      ATIP isoforms are expressed in a distinct manner, whereupon isoform 1 and 4 are
      correlated to cardiovascular, lung, and limb bud development and isoform 3 is
      restricted to brain and eye development. Interestingly, Mtus1 expression is not
      necessarily correlated to Agtr2 expression, suggesting novel but yet unknown
      functions for ATIP, independent of AT2 signaling. CONCLUSIONS: ATIPs seem to be
      mainly involved in the developmental regulation of the cardiovascular system and
      may act in different AT2-dependent and -independent manners. Hence, these results
      deliver valuable information to further elucidate the different functions of
      ATIPs in the processes of mammalian development.

PMID- 24288151
TI  - Transport, electrochemical and thermophysical properties of two N-donor
      functionalised ionic liquids.
AB  - Two N-donor-functionalised ionic liquids (ILs), 1-ethyl-1,4-dimethylpiperazinium
      bis(trifluoromethylsulfonyl)amide (1) and 1-(2-dimethylaminoethyl)
      dimethylethylammonium bis(trifluoromethylsulfonyl)amide (2), were synthesised and
      their electrochemical and transport properties measured. The data were compared
      with the benchmark system, N-butyl-N-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)amide (3). Marked differences in thermal and
      electrochemical stability were observed between the two tertiary-amine
      functionalised salts and the non-functionalised benchmark. The former are up to
      170 K and 2 V less stable than the structural counterpart lacking a tertiary
      amine function. The ion self-diffusion coefficients (Di ) and molar
      conductivities (Lambda) are higher for the IL with an open-chain cation (2) than
      that with a cyclic cation (1), but less than that with a non-functionalised,
      heterocyclic cation (3). The viscosities (eta) show the opposite behaviour. The
      Walden [Lambda[proportionality](1/eta)(t) ] and Stokes-Einstein [Di
      /T)[proportionality](1/eta)(t) ] exponents, t, are very similar for the three
      salts, 0.93-0.98 (+/-0.05); that is, the self-diffusion coefficients and
      conductivity are set by eta. The Di for 1 and 2 are the same, within experimental
      error, at the same viscosity, whereas Lambda for 1 is approximately 13% higher
      than that of 2. The diffusion and molar conductivity data are consistent, with a
      slope of 0.98+/-0.05 for a plot of ln(LambdaT) against ln(D+ +D- ). The Nernst
      Einstein deviation parameters (Delta) are such that the mean of the two like-ion
      VCCs is greater than that of the unlike ions. The values of Delta are 0.31, 0.36
      and 0.42 for 3, 1 and 2, respectively, as is typical for ILs, but there is some
      subtlety in the ion interactions given 2 has the largest value. The distinct
      diffusion coefficients (DDC) follow the order D(d)__ < D(d)++ < D(d)+_, as is
      common for [Tf2N](-) salts. The ion motions are not correlated as in an
      electrolyte solution: instead, there is greater anti-correlation between the
      velocities of a given anion and the overall ensemble of anions in comparison to
      those for the cationic analogue, the anti-correlation for the velocities of which
      is in turn greater than that for a given ion and the ensemble of oppositely
      charged ions, an observation that is due to the requirement for the conservation
      of momentum in the system. The DDC also show fractional SE behaviour with t~0.95.

PMID- 24288150
TI  - Shindigs, brunches, and rodeos: the neural basis of event words.
AB  - Events (e.g., "running" or "eating") constitute a basic type within human
      cognition and human language. We asked whether thinking about events, as compared
      to other conceptual categories, depends on partially independent neural circuits.
      Indirect evidence for this hypothesis comes from previous studies showing
      elevated posterior temporal responses to verbs, which typically label events.
      Neural responses to verbs could, however, be driven either by their grammatical
      or by their semantic properties. In the present experiment, we separated the
      effects of grammatical class (verb vs. noun) and semantic category (event vs.
      object) by measuring neural responses to event nouns (e.g., "the hurricane").
      Participants rated the semantic relatedness of event nouns, as well as of two
      categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the
      acorn")-and three categories of verbs-manner of motion (e.g., "to roll"),
      emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has
      previously been observed, we found larger responses to verbs than to object nouns
      in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially,
      we also found that the LMTG responds more to event than to object nouns. These
      data suggest that part of the posterior lateral temporal response to verbs is
      driven by their semantic properties. By contrast, a more superior region, at the
      junction of the temporal and parietal cortices, responded more to verbs than to
      all nouns, irrespective of their semantic category. We concluded that the neural
      mechanisms engaged when thinking about event and object categories are partially
      dissociable. 

PMID- 24288152
TI  - Synthesis of five- and six-coordinate tris(pentafluoroethyl)fluorosilicates.
AB  - The research area of perfluoroalkylsilanes is still in its infancy. Although
      there are already many examples of difluorotriorganylsilicates, the first example
      of a completely characterized trifluorotriorganylsilicate is presented, the
      dianion [Si(C2 F5 )3 F3 ](2-) . The strongly electron-withdrawing influence of
      the pentafluoroethyl groups appears to be a fundamental cause of the stability of
      this compound. This dianion is also the first structurally characterized example
      of a tris(pentafluoroethyl)silicon compound. The synthesis and complete
      characterization of [PPh4 ]2 [Si(C2 F5 )3 F3 ] and [PPh4 ][Si(C2 F5 )3 F2 ] along
      with the precursor [H(OEt2 )2 ][Si(C2 F5 )3 F2 ] was achieved from SiCl4 and LiC2
      F5 . 

PMID- 24288153
TI  - Isolation and characterization of mesenchymal stem cells derived from fetal
      bovine liver.
AB  - Bovine liver-derived mesenchymal stem cells (bLMSCs) were isolated from the liver
      tissue of 4-6 months old fetal calf, and then characterized by immunofluorescence
      and RT-PCR. We found that primary bLMSCs could be subcultured to 44 passages, the
      total culture time in vitro was 192 days. The results of surface antigen
      detection showed that bBMSCs expressed CD29, CD44, CD73, CD90, CD106 and CD166
      but not expressed endothelial cells and hematopoietic cells specific marker CD34,
      CD45 and BLA-DR. The results of growth kinetics, colony-forming cell assay and
      cell cycle analysis indicated that the fetal bovine LMSCs had good proliferation
      ability in vitro. The cells from passages 7 were successfully induced to
      differentiate into osteoblasts, adipocytes and chondrocytes. The results indicate
      the potential for multi-lineage differentiation of bLMSCs that may represent an
      ideal candidate for cellular transplantation therapy.

PMID- 24288154
TI  - Endometrial resection and ablation versus hysterectomy for heavy menstrual
      bleeding.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB), which includes both menorrhagia and
      metrorrhagia, is an important cause of ill health in women. Surgical treatment of
      HMB often follows failed or ineffective medical therapy. The definitive treatment
      is hysterectomy, but this is a major surgical procedure with significant physical
      and emotional complications, as well as social and economic costs. Several less
      invasive surgical techniques (e.g. transcervical resection of the endometrium
      (TCRE), laser approaches) and various methods of endometrial ablation have been
      developed with the purpose of improving menstrual symptoms by removing or
      ablating the entire thickness of the endometrium. OBJECTIVES: The objective of
      this review is to compare the effectiveness, acceptability and safety of
      techniques of endometrial destruction by any means versus hysterectomy by any
      means for the treatment of heavy menstrual bleeding. SEARCH METHODS: Electronic
      searches for relevant randomised controlled trials (RCTs) targeted but were not
      limited to the following: the Cochrane Menstrual Disorders and Subfertility Group
      Register of Trials, MEDLINE, EMBASE, PsycINFO and the Cochrane CENTRAL register
      of trials. Attempts were made to identify trials by examining citation lists of
      review articles and guidelines and by performing handsearching. Searches were
      performed in 2007, 2008 and 2013. SELECTION CRITERIA: Included in the review were
      any RCTs that compared techniques of endometrial destruction by any means with
      hysterectomy by any means for the treatment of heavy menstrual bleeding in
      premenopausal women. DATA COLLECTION AND ANALYSIS: Two review authors
      independently searched for studies, extracted data and assessed risk of bias.
      Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for
      continuous outcomes were estimated from the data. Outcomes analysed included
      improvement in menstrual blood loss, satisfaction, change in quality of life,
      duration of surgery and hospital stay, time to return to work, adverse events and
      requirements for repeat surgery due to failure of the initial surgical treatment.
      MAIN RESULTS: Eight RCTs that fulfilled the inclusion criteria for this review
      were identified. For two trials, the review authors identified multiple
      publications that assessed different outcomes at different postoperative time
      points for the same women.An advantage in favour of hysterectomy compared with
      endometrial ablation was observed in various measures of improvement in bleeding
      symptoms and satisfaction rates. A slightly lower proportion of women who
      underwent endometrial ablation perceived improvement in bleeding symptoms at one
      year (RR 0.89, 95% confidence interval (CI) 0.85 to 0.93, four studies, 650
      women, I(2) = 31%), at two years (RR 0.92, 95% CI 0.86 to 0.99, two studies, 292
      women, I(2) = 53%) and at four years (RR 0.93, 95% CI 0.88 to 0.99, two studies,
      237 women, I(2) = 79%). The same group of women also showed improvement in
      pictorial blood loss assessment chart (PBAC) score at one year (MD 24.40, 95% CI
      16.01 to 32.79, one study, 68 women) and at two years (MD 44.00, 95% CI 36.09 to
      51.91, one study, 68 women). Repeat surgery resulting from failure of the initial
      treatment was more likely to be needed after endometrial ablation than after
      hysterectomy at one year (RR 14.9, 95% CI 5.2 to 42.6, six studies, 887 women,
      I(2) = 0%), at two years (RR 23.4, 95% CI 8.3 to 65.8, six studies, 930 women,
      I(2) = 0%), at three years (RR 11.1, 95% CI 1.5 to 80.1, one study, 172 women)
      and at four years (RR 36.4, 95% CI 5.1 to 259.2, one study, 197 women). Most
      adverse events, both major and minor, were significantly more likely after
      hysterectomy during hospital stay. Women who had a hysterectomy were more likely
      to experience sepsis (RR 0.2, 95% CI 0.1 to 0.3, four studies, 621 women, I(2) =
      62%), blood transfusion (RR 0.2, 95% CI 0.1 to 0.6, four studies, 751 women, I(2)
      = 0%), pyrexia (RR 0.2, 95% CI 0.1 to 0.4, three studies, 605 women, I(2) = 66%),
      vault haematoma (RR 0.1, 95% CI 0.04 to 0.3, five studies, 858 women, I(2) = 0%)
      and wound haematoma (RR 0.03, 95% CI 0.00 to 0.5, one study, 202 women) before
      hospital discharge. After discharge from hospital, the only difference that was
      reported for this group was a higher rate of infection (RR 0.2, 95% CI 0.1 to
      0.5, one study, 172 women).For some outcomes (such as a woman's perception of
      bleeding and proportion of women requiring further surgery for HMB), a low GRADE
      score was generated, suggesting that further research in these areas is likely to
      change the estimates. AUTHORS' CONCLUSIONS: Endometrial resection and ablation
      offers an alternative to hysterectomy as a surgical treatment for heavy menstrual
      bleeding. Both procedures are effective, and satisfaction rates are high.
      Although hysterectomy is associated with longer operating time (particularly for
      the laparoscopic route), a longer recovery period and higher rates of
      postoperative complications, it offers permanent relief from heavy menstrual
      bleeding. The initial cost of endometrial destruction is significantly lower than
      that of hysterectomy, but, because retreatment is often necessary, the cost
      difference narrows over time.

PMID- 24288155
TI  - Functional and evolutionary aspects of axial stability in euarchontans and other
      mammals.
AB  - The presence of a stable thoracolumbar region, found in many arboreal mammals, is
      considered advantageous for bridging and cantilevering between discontinuous
      branches. However, no study has directly explored the link between osteological
      features cited as enhancing axial stability and the frequency of cantilevering
      and bridging behaviors in a terminal branch environment. To fill this gap, we
      collected metric data on costal and vertebral morphology of primate and
      nonprimate mammals known to cantilever and bridge frequently and those that do
      not. We also quantified the frequency and duration of cantilevering and bridging
      behaviors using experimental setups for species that have been reported to show
      differences in use of small branches and back anatomy (Caluromys philander, Loris
      tardigradus, Monodelphis domestica, and Cheirogaleus medius). Phylogenetically
      corrected principal component analysis reveals that taxa employing frequent
      bridging and cantilevering (C. philander and lorises) also exhibit reduced
      intervertebral and intercostal spaces, which can serve to increase thoracolumbar
      stability, when compared to closely related species (M. domestica and C. medius).
      We observed C. philander cantilevering and bridging significantly more often than
      M. domestica, which never cantilevered or crossed any arboreal gaps. Although no
      difference in the frequency of cantilevering was observed between L. tardigradus
      and C. medius, the duration of cantilevering bouts was significantly greater in
      L. tardigradus. These data suggest that osteological features promoting axial
      rigidity may be part of a morpho-behavioral complex that increases stability in
      mammals moving and foraging in a terminal branch environment.

PMID- 24288156
TI  - In vitro analysis of the antibacterial effect of nanohydroxyapatite-ZnO
      composites.
AB  - Hydroxyapatite (HA) is a biocompatible and bioactive synthetic material for
      biomedical applications as it binds to bone and enhances bone tissue formation.
      Particularly, nanophased HA can mimic the dimensions of constituent components of
      natural tissues; can modulate enhanced osteoblast adhesion and resorption with
      long-term functionality of tissue engineered implants. However, HA does not
      inhibit bacteria from adhering onto its surface, and this has implications in the
      bone healing process required for patient recovery, since infection can lead to
      the implant failure. In the present work a composite that combines the favorable
      biological characteristics of nanohydroxyapatite (nanoHA) and, simultaneously,
      possesses antimicrobial activity as expressed by ZnO was synthesized. To
      determine whether the size of ZnO particles was playing an important role in
      inhibiting bacterial growth, ZnO particle of different sizes (from the microscale
      down to the nanoscale) and concentration were incorporated into nanoHA and
      tested. The composite samples were characterized by SEM, FT-IR, XRD, XPS and zeta
      potential. The antibacterial activity of the composites was investigated, as well
      as the biofilm formation, using both Gram-positive (Staphylococcus aureus) and
      Gram-negative (Escherichia coli) microorganisms. The characterization revealed
      that ZnO particles were dispersed homogeneously within the nanoHA matrix. The
      composites antibacterial activity increased with decreasing ZnO particle size and
      increasing concentration. Biofilm formation tests revealed that the nanoHA-ZnO
      composites exhibit a strong effect against the common pathogens S. aureus and E.
      coli.

PMID- 24288157
TI  - Adjuvant antiarrhythmic therapy in patients with implantable cardioverter
      defibrillators.
AB  - The risk of sudden cardiac death from ventricular fibrillation or ventricular
      tachycardia in patients with cardiomyopathy related to structural heart disease
      has been favorably impacted by the wide adaptation of implantable cardioverter
      defibrillators (ICDs) for both primary and secondary prevention. Unfortunately,
      after ICD implantation both appropriate and inappropriate ICD therapies are
      common. ICD shocks in particular can have significant effects on quality of life
      and disease-related morbidity and mortality. While not indicated for primary
      prevention of ICD therapies, beta-blockers and antiarrhythmic drugs are a
      cornerstone for secondary prevention of them. This review will summarize our
      current understanding of adjuvant antiarrhythmic drug therapy in ICD patients.
      The review will also discuss the roles of nonantiarrhythmic drug approaches that
      are used in isolation and in combination with antiarrhythmic drugs to reduce
      subsequent risk of ICD shocks. 

PMID- 24288158
TI  - Preconcentration of organochlorine pesticides in aqueous samples by dispersive
      liquid-liquid microextraction based on solidification of floating organic drop
      after SPE with multiwalled carbon nanotubes.
AB  - SPE joined with dispersive liquid-liquid microextraction based on solidification
      of floating organic drop (DLLME-SFO) as a novel technique combined with GC with
      electron-capture detection has been developed as a preconcentration technique for
      the determination of organochlorine pesticides (OCPs) in water samples. Aqueous
      samples were loaded onto multiwalled carbon nanotubes as sorbent. After the
      elution of the desired compounds from the sorbent by using acetone, the DLLME-SFO
      technique was performed on the obtained solution. Variables affecting the
      performance of both steps such as sample solution flow rate, breakthrough volume,
      type and volume of the elution, type and volume of extraction solvent and salt
      addition were studied and optimized. The new method provided an ultra enrichment
      factor (8280-28221) for nine OCPs. The calibration curves were linear in the
      range of 0.5-1000 ng/L, and the LODs ranged from 0.1-0.39 ng/L. The RSD, for 0.01
      MUg/L of OCPs, was in the range of 1.39-13.50% (n = 7). The recoveries of method
      in water samples were 70-113%. 

PMID- 24288159
TI  - Characterizing bias in population genetic inferences from low-coverage sequencing
      data.
AB  - The site frequency spectrum (SFS) is of primary interest in population genetic
      studies, because the SFS compresses variation data into a simple summary from
      which many population genetic inferences can proceed. However, inferring the SFS
      from sequencing data is challenging because genotype calls from sequencing data
      are often inaccurate due to high error rates and if not accounted for, this
      genotype uncertainty can lead to serious bias in downstream analysis based on the
      inferred SFS. Here, we compare two approaches to estimate the SFS from sequencing
      data: one approach infers individual genotypes from aligned sequencing reads and
      then estimates the SFS based on the inferred genotypes (call-based approach) and
      the other approach directly estimates the SFS from aligned sequencing reads by
      maximum likelihood (direct estimation approach). We find that the SFS estimated
      by the direct estimation approach is unbiased even at low coverage, whereas the
      SFS by the call-based approach becomes biased as coverage decreases. The
      direction of the bias in the call-based approach depends on the pipeline to infer
      genotypes. Estimating genotypes by pooling individuals in a sample (multisample
      calling) results in underestimation of the number of rare variants, whereas
      estimating genotypes in each individual and merging them later (single-sample
      calling) leads to overestimation of rare variants. We characterize the impact of
      these biases on downstream analyses, such as demographic parameter estimation and
      genome-wide selection scans. Our work highlights that depending on the pipeline
      used to infer the SFS, one can reach different conclusions in population genetic
      inference with the same data set. Thus, careful attention to the analysis
      pipeline and SFS estimation procedures is vital for population genetic
      inferences. 

PMID- 24288161
TI  - Human-specific hypomethylation of CENPJ, a key brain size regulator.
AB  - Both the enlarged brain and concurrent highly developed cognitive skills are
      often seen as distinctive characteristics that set humans apart from other
      primates. Despite this obvious differentiation, the genetic mechanisms that
      underlie such human-specific traits are not clearly understood. In particular,
      whether epigenetic regulations may play a key role in human brain evolution
      remain elusive. In this study, we used bisulfite sequencing to compare the
      methylation patterns of four known genes that regulate brain size (ASPM,
      CDK5RAP2, CENPJ, and MCPH1) in the prefrontal cortex among several primate
      species spanning the major lineages of primates (i.e., humans, great apes, lesser
      apes, and Old World monkeys). The results showed a human-specific hypomethylation
      in the 5' UTR of CENPJ in the brain, where methylation levels among humans are
      only about one-third of those found among nonhuman primates. Similar methylation
      patterns were also detected in liver, kidney, and heart tissues, although the
      between-species differences were much less pronounced than those in the brain.
      Further in vitro methylation assays indicated that the methylation status of the
      CENPJ promoter could influence its expression. We also detected a large
      difference in CENPJ expression in the human and nonhuman primate brains of both
      adult individuals and throughout the major stages of fetal brain development. The
      hypomethylation and comparatively high expression of CENPJ in the central nervous
      system of humans suggest that a human-specific--and likely heritable--epigenetic
      modification likely occurred during human evolution, potentially leading to a
      much larger neural progenitor pool during human brain development, which may have
      eventually contributed to the dramatically enlarged brain and highly developed
      cognitive abilities associated with humans.

PMID- 24288162
TI  - Differential localization of NT-3 and TrpM5 in glomeruli of the olfactory bulb of
      mice.
AB  - Olfactory sensory neurons that express transient receptor potential channel M5
      (TrpM5) or neurotrophin-3 (NT-3) project to defined clusters of glomeruli
      situated ventrally in the main olfactory bulb. Using genetically labeled mice, we
      investigated whether expression of NT-3-driven betagal and TrpM5-driven GFP
      marked overlapping sets of glomeruli and whether expression of these markers was
      coordinated. Our results indicate that these markers largely characterize
      independent sets of olfactory sensory neuron axons and glomeruli. Further, in
      glomeruli in which both TrpM5-GFP and NT-3-betagal labeled axons occur, they are
      expressed independently. The nature of staining for these two markers also
      differs within glomeruli. Within each labeled TrpM5-positive glomerulus, the
      level of TrpM5-GFP expression was similar throughout the glomerular neuropil. In
      contrast, NT-3-driven betagal expression levels are heterogeneous even within
      heavily labeled glomeruli. In addition, a population of very small TrpM5-GFP
      positive glomeruli is apparent while no similar populations of NT-3-betagal
      glomeruli are evident. Taken together, these data suggest that TrpM5 and NT-3
      characterize two largely independent receptor populations both conveying odorant
      information to the ventral olfactory bulb.

PMID- 24288163
TI  - A formulation of cell surviving fraction after radiation exposure.
AB  - Local energy transfer from electrons generated in biotissues that are exposed to
      ionizing radiation is fundamental to cell damage. Our aim in this investigation
      was to quantify the probability of cell mortality associated with the damage by
      electrons and the repair processes in the cell nucleus, envisaging a new
      interpretation of the cell surviving fraction (SF). We introduced a SF formula
      for cells exposed to X-rays, which is given as a linear combination of the
      Poisson distributions about the number of long-lived lesions per nucleus and
      their "non-lethal probabilities", to show the non-linearity of log SF as a
      function of dose. The model selection was rated by a statistical index, Akaike's
      information criterion (AIC). It was shown that the new formula is suitable for
      describing cell survival and explicitly takes account of the non-lethality in
      damage-processing pathways of the cells. 

PMID- 24288164
TI  - Employer attitudes towards the work inclusion of people with disability.
AB  - BACKGROUND: This study examines the importance of work in life of people with
      disability and then focuses on employer attitudes towards these people. In the
      light of Stone and Colella's model, the study examines the employer attitudes and
      the role of variables such as type of disability, employer experience in the
      hiring of persons with disabilities, the description of hypothetical hirees with
      disabilities, the ways in which employers evaluate work performance and social
      acceptability, and the work tasks that they consider appropriate for workers with
      disability. METHOD: Eighty employers were randomly assigned to standard condition
      (candidates with disability were presented by referring to the disability they
      presented) or positive condition (candidates were presented with reference to
      their strengths). RESULTS: It was found that the type of disability and its
      presentation influence employer attitudes. In addition, realistic and
      conventional tasks were considered appropriate for hirees with disabilities.
      CONCLUSIONS: Implications were discussed.

PMID- 24288165
TI  - Additional mandibles of Rangwapithecus gordoni, an early Miocene catarrhine from
      the Tinderet localities of Western Kenya.
AB  - Two catarrhine mandibles and five isolated teeth have been discovered from Early
      Miocene localities in Western Kenya. One mandible comes from the well-known
      locality of Songhor whereas the other is from a newly discovered locality, Lower
      Kapurtay, located near Songhor. The mandibles both can clearly be assigned to the
      species Rangwapithecus gordoni based on molar morphology, which is unique among
      Early Miocene catarrhines. The isolated specimens can be assigned to
      Rangwapithecus based on their similarities in morphology to the homologues
      preserved in the two mandibles. These specimens provide important new information
      about the dentognathic morphology of Rangwapithecus, which is described in
      detail. The mandible from Songhor (KNM-SO 22228) represents the first definitive
      female mandible of Rangwapithecus. The Lower Kapurtay mandible (KNM-KT 31234)
      appears to be male but is much smaller than another recently described male
      mandible of this species (KNM-SO 17500) and the type maxilla (KNM-SO 700). These
      specimens enable a reassessment of the attributions of all other mandibles and
      isolated lower teeth of Rangwapithecus, and we present a complete hypodigm of the
      mandibular and lower dental material for the species. Finally, we provide some
      additions to the diagnosis of Rangwapithecus gordoni based on previously unknown
      morphology.

PMID- 24288166
TI  - Pt-Pd-Co trimetallic alloy network nanostructures with superior electrocatalytic
      activity towards the oxygen reduction reaction.
AB  - Pt alloy nanostructures show great promise as electrocatalysts for the oxygen
      reduction reaction (ORR) in fuel cell cathodes. Herein, three-dimensional (3D) Pt
      Pd-Co trimetallic network nanostructures (TNNs) with a high degree of alloying
      are synthesized through a room temperature wet chemical synthetic method by using
      K2 PtCl4 /K3 Co(CN)6 -K2 PdCl4 /K3 Co(CN)6 mixed cyanogels as the reaction
      precursor in the absence of surfactants and templates. The size, morphology, and
      surface composition of the Pt-Pd-Co TNNs are investigated by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), selected-area electron
      diffraction (SAED), energy dispersive spectroscopy (EDS), EDS mapping, X-ray
      diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The 3D backbone
      structure, solid nature, and trimetallic properties of the mixed cyanogels are
      responsible for the 3D structure and high degree of alloying of the as-prepared
      products. Compared with commercially available Pt black, the Pt-Pd-Co TNNs
      exhibit superior electrocatalytic activity and stability towards the ORR, which
      is ascribed to their unique 3D structure, low hydroxyl surface coverage and alloy
      properties. 

PMID- 24288167
TI  - Blocked bacteria escape by ATRP grafting of a PMMA shell on PVA microparticles.
AB  - This paper reports on the preparation and characterization of living composites
      consisting of poly(vinylalcohol) (PVA) hydrogel microparticles with living
      bacteria and a shell of poly(methyl methacrylate) (PMMA). The grafting of the
      PMMA shell is accomplished in the presence of living bacteria by surface
      polymerization of PMMA using atom transfer radical polymerization (ATRP). The
      PMMA shell prevents the uncontrolled bacterial escape from the hydrogel
      microparticles, which otherwise marks a major problem of these composites. The
      encapsulation of microparticles with living bacteria by PMMA retards bacteria
      escape upon contact to water for >20 d. The functionality of the PMMA shell is
      proven both by the release of fluorescein in buffer and an altered release time
      of bacteria in buffer solution.

PMID- 24288168
TI  - Gold-catalyzed heterogeneous aerobic dehydrogenative amination of alpha,beta
      unsaturated aldehydes to enaminals.
AB  - Although enaminals (beta-enaminals) are very important compounds and have been
      utilized as useful synthons for various important compounds, they have been
      synthesized through non-green and/or limited procedures until now. Herein, we
      have successfully developed a green synthetic procedure using a heterogeneous
      catalyst. In the presence of gold nanoparticles supported on manganese-oxide
      based octahedral molecular sieves OMS-2 (Au/OMS-2), dehydrogenative amination of
      alpha,beta-unsaturated aldehydes with amines proceeded efficiently, with the
      corresponding enaminals isolated in moderate to high yields (50-97 %). The
      catalysis was truly heterogeneous, and Au/OMS-2 could be reused. Furthermore, the
      formal Wacker-type oxidation of alpha,beta-unsaturated aldehydes to enaminones
      has been realized. 

PMID- 24288169
TI  - Degradable thiol-acrylate hydrogels as tunable matrices for three-dimensional
      hepatic culture.
AB  - A degradable poly(ethylene glycol)-diacrylate (PEGDA) hydrogel system was
      developed using simple macromer formulations and visible light initiated thiol
      acrylate photopolymerization. In addition to PEGDA, other components in this
      gelation system include eosin-Y as a photo-sensitizer, bi-functional thiol
      (dithiothreitol, DTT) as a dual-purpose co-initiator and cross-linker, and N
      vinylpyrrolidone (NVP) as a co-monomer. Gelation was achieved through a mixed
      mode step-chain growth polymerization mechanism under bright visible light
      exposure. Increasing photo-sensitizer or NVP concentrations accelerated photo
      crosslinking and increased final gel stiffness. Increasing bi-functional thiol
      content in the prepolymer solution only increased gel stiffness to some degree.
      As the concentration of thiol surpassed certain range, thiol-mediated chain
      transfer events caused thiol-acrylate gels to form with lower degree of cross
      linking. Pendant peptide, such as integrin ligand RGDS, was more effectively
      immobilized in the network via a thiol-acrylate reaction (using thiol-bearing
      peptide Ac-CRGDS. Underline indicates cross-linkable motif) than through homo
      polymerization of acrylated peptide (e.g., acryl-RGDS). The incorporation of
      pendant peptide comes with the expense of a lower degree of gel cross-linking,
      which was rectified by increasing co-monomer NVP content. Without the use of any
      readily degradable macromer, these visible light initiated mixed-mode cross
      linked hydrogels degraded hydrolytically due to the formation of thiol-ether
      ester bonds following thiol-acrylate reactions. An exponential growth
      relationship was identified between the hydrolytic degradation rate and
      bifunctional thiol content in the prepolymer solution. Finally, we evaluated the
      cytocompatibility of these mixed-mode cross-linked degradable hydrogels using in
      situ encapsulation of hepatocellular carcinoma Huh7 cells. Encapsulated Huh7
      cells remained alive and proliferated as time to form cell clusters. The addition
      of NVP at a higher concentration (0.3%) did not affect Huh7 cell viability but
      resulted in reduction of cell metabolic activity, which was accompanied by an
      elevated urea secretion from the encapsulated cells.

PMID- 24288170
TI  - The effect of miRNA-122 in regulating fat deposition in a cell line model.
AB  - Accumulating evidence supports the role of miR-122 in fatty liver disease. We
      investigated miR-122 expression in a steatotic hepatocyte model, the effect of
      miR-122 over-expression and inhibition in the pathogenesis. Human hepatic cell
      line L02 was induced with oleic acid to establish the steatotic hepatocyte model.
      Intracellular lipid content was observed with laser scanning confocal microscope
      (LSCM), and triglyceride content was determined with kits. Total RNA was
      extracted and reversely transcribed into cDNA. miR-122 expression was measured
      using qRT-PCR. Subsequently, miR-122 mimic and miR-122 inhibitor were transfected
      into steatotic hepatocytes to observe their effect on intracellular lipid
      content. The lipid fluorescence intensity and triglyceride content within the
      steatotic hepatocytes were significantly higher than those in normal control
      (860.01 +/- 26.52 vs. 257.77 +/- 29.69 and 3.47 +/- 0.12 vs. 1.85 +/- 0.02 at 24
      h) (P < 0.01). miR-122 expression in steatotic hepatocytes was down-regulated
      compared with that in control (2-DeltaCt value: 0.0286 +/- 0.0078 vs. 0.0075 +/-
      0.0012) (P ? 0.01). After transfection, miR-122 expression (2-DeltaCt value) in
      the miR-122 mimic group increased 2.96-fold compared with that in control, and
      its lipid fluorescence intensity was significantly lower than that in control
      (790.92 +/- 46.72 vs. 1,022.16 +/- 49.66) (P < 0.01). Nevertheless, miR-122
      expression decreased 3.45-fold in the miR-122 inhibitor group compared with that
      in control, and its fluorescence intensity was significantly higher than that in
      control (1,386.49 +/- 40.34 vs 1,022.16 +/- 49.66)(P ? 0.01). We concluded that
      miR-122 was down-regulated in steatotic hepatocytes model. The pathogenesis of
      hepatocyte steatosis was enhanced by miR-122 mimic and reduced with miR-122
      inhibitor.

PMID- 24288171
TI  - Grammatical context constrains lexical competition in spoken word recognition.
AB  - When perceiving spoken language, listeners must match the incoming acoustic
      phonetic input to lexical representations in memory. Models that quantify this
      process propose that the input activates multiple lexical representations in
      parallel and that these activated representations compete for recognition (Weber
      & Scharenborg, 2012). In two experiments, we assessed how grammatically
      constraining contexts alter the process of lexical competition. The results
      suggest that grammatical context constrains the lexical candidates that are
      activated to grammatically appropriate competitors. Stimulus words with little
      competition from items of the same grammatical class benefit more from the
      addition of grammatical context than do words with more within-class competition.
      The results provide evidence that top-down contextual information is integrated
      in the early stages of word recognition. We propose adding a grammatical class
      level of analysis to existing models of word recognition to account for these
      findings. 

PMID- 24288172
TI  - Promoting factors of physical and mental development in early infancy: a
      comparison of preterm delivery/low birth weight infants and term infants.
AB  - OBJECTIVE: The aim of this study was to assess correlations between various
      factors and the physical and mental development of 4-month-old infants using a
      multi-faceted evaluation approach. METHODS: A total of 1,402 self-administered
      questionnaires were distributed to consenting mothers of infants who had
      undergone a 4-month health checkup in Hiroshima prefecture, Japan. The
      questionnaires included items from the Japan Child and Family Research Institute
      Child Rearing Support Questionnaire and the KIDS type A test. Of the 421
      completed questionnaires on mother-child pairs that were returned, 318 met the
      inclusion criteria and were eligible for further analysis. RESULTS: Comparison
      between infants in a preterm delivery or low birth weight (LBW) group (preterm
      and/or LBW group; n = 31) and a term delivery appropriate-weight for date (AFD)
      infant group (term AFD group; n =287) revealed that the preterm and/or LBW group
      had significantly higher mother child-rearing anxiety and difficult baby scores,
      along with significantly lower infant development and motor skill scores. Within
      the term AFD group, infants of primiparous mothers had significantly higher
      scores for motor skill and sociability with adults than those of multiparous
      mothers. Language comprehension scores were significantly higher in infants that
      were exclusively breast-fed than those formula-fed or combined breast-fed and
      formula-fed. Verbalization scores of infants whose mothers worked were
      significantly higher than those of infants whose mothers did not work. Infants
      with siblings aged <4 years exhibited significantly lower scores for motor
      skills, verbalization, and sociability with adults than infants without siblings
      or with siblings aged at least 5 years. In particular, we found that a mother's
      child-rearing anxiety was related to many areas of infant development.
      CONCLUSIONS: Evaluating the absence or presence of such factors and conducting
      preventive treatment could promote healthy infant development.

PMID- 24288174
TI  - Risk of venous thrombosis varies with different types of combined oral
      contraceptives.

PMID- 24288175
TI  - Tranexamic acid reduces surgical bleeding: does one size fit all?

PMID- 24288173
TI  - Subcortical connections of area V4 in the macaque.
AB  - Area V4 has numerous, topographically organized connections with multiple
      cortical areas, some of which are important for spatially organized visual
      processing, and others which seem important for spatial attention. Although the
      topographic organization of V4's connections with other cortical areas has been
      established, the detailed topography of its connections with subcortical areas is
      unclear. We therefore injected retrograde and anterograde tracers in different
      topographical regions of V4 in nine macaques to determine the organization of its
      subcortical connections. The injection sites included representations ranging
      from the fovea to far peripheral eccentricities in both the upper and lower
      visual fields. The topographically organized connections of V4 included
      bidirectional connections with four subdivisions of the pulvinar, two
      subdivisions of the claustrum, and the interlaminar portions of the lateral
      geniculate nucleus, and efferent projections to the superficial and intermediate
      layers of the superior colliculus, the thalamic reticular nucleus, and the
      caudate nucleus. All of these structures have a possible role in spatial
      attention. The nontopographic, or converging, connections included bidirectional
      connections with the lateral nucleus of the amygdala, afferent inputs from the
      dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus
      basalis of Meynert, and efferent projections to the putamen. Any role of these
      structures in attention may be less spatially specific.

PMID- 24288176
TI  - Palladium-catalyzed ortho-selective C-H deuteration of arenes: evidence for
      superior reactivity of weakly coordinated palladacycles.
AB  - We disclose a protocol for the palladium-catalyzed ortho-selective C-H
      deuteration of arenes. Phenylacetic acids and benzoic acids are suitable
      substrates for this reaction. This reaction offers a catalytic route to ortho
      deuterated phenylacetic acids and benzoic acids and demonstrates the sharp
      difference in reactivity of palladacycle intermediates held together by weak and
      strong coordination.

PMID- 24288177
TI  - Synthesis and photophysics of a new family of fluorescent 9-alkyl-substituted
      xanthenones.
AB  - 9-Alkyl xanthenones with different aliphatic pendant groups have been easily
      prepared by means of nucleophilic addition of the corresponding Grignard
      derivative to a tert-butyldimethylsilyl ether (TBDMS)-protected 3,6-dihydroxy
      xanthenone. The photophysical behavior of the new dyes has been explored by using
      absorption, steady-state-, and time-resolved fluorescence measurements. We
      determined the equilibrium constants, visible spectral characteristics,
      fluorescence quantum yield, and decay times. Remarkably, they retain similar
      fluorescent properties of fluorescein including the characteristic phosphate
      mediated excited-state proton-transfer (ESPT) reaction. 6-Hydroxy-9-isopropyl-3H
      xanthen-3-one (5) was investigated in living cells; it presented a good
      permeability and efficient accumulation inside the cytosol. For the first time,
      we reported that the requirement of an aryl group at C-9 is no longer needed and
      new fluorescent sensors can be therefore easily developed. 

PMID- 24288179
TI  - MicroRNA-590 promotes cervical cancer cell growth and invasion by targeting CHL1.
AB  - MicroRNAs (miRNAs) may function as oncogenes or tumor suppressors. Here, we
      identified that miR-590-5p was up-regulated in human cervical cancer. Over
      expression of miR-590-5p promoted cervical cancer cell growth, cell cycle and
      invasion via Growth curve, Colony formation, FACS and Transwell assays in HeLa
      and C33A cell lines. Subsequently, CHL1 was identified as a potential miR-590-5p
      target by bioinformatics analysis. Moreover, we showed that CHL1 was negatively
      regulated by miR-590-5p at the posttranscriptional level, via a specific target
      site within the 3'UTR by luciferase reporter assay. Furthermore, the mRNA and
      protein levels of CHL1 in cervical cancer cells were downregulated by miR-590-5p.
      And we identified the cell phenotype altered by miR-590-5p can be rescued by over
      expression of CHL1. Therefore, our findings suggest that miR-590-5p acts as an
      oncogene by targeting the CHL1 gene and promotes cervical cancer proliferation.
      The findings of this study contribute to current understanding of the functions
      of miR-590-5p in cervical cancer.

PMID- 24288178
TI  - In vivo baseline measurements of hip joint range of motion in suspensory and
      nonsuspensory anthropoids.
AB  - Hominoids and atelines are known to use suspensory behaviors and are assumed to
      possess greater hip joint mobility than nonsuspensory monkeys, particularly for
      range of abduction. This assumption has greatly influenced how extant and fossil
      primate hip joint morphology has been interpreted, despite the fact that there
      are no data available on hip mobility in hominoids or Ateles. This study uses in
      vivo measurements to test the hypothesis that suspensory anthropoids have
      significantly greater ranges of hip joint mobility than nonsuspensory
      anthropoids. Passive hip joint mobility was measured on a large sample of
      anesthetized captive anthropoids (nonhuman hominids = 43, hylobatids = 6,
      cercopithecids = 43, Ateles = 6, and Cebus = 6). Angular and linear data were
      collected using goniometers and tape measures. Range of motion (ROM) data were
      analyzed for significant differences by locomotor group using ANOVA and
      phylogenetic regression. The data demonstrate that suspensory anthropoids are
      capable of significantly greater hip abduction and external rotation. Degree of
      flexion and internal rotation were not larger in the suspensory primates,
      indicating that suspension is not associated with a global increase in hip
      mobility. Future work should consider the role of external rotation in abduction
      ability, how the physical position of the distal limb segments are influenced by
      differences in ROM proximally, as well as focus on bony and soft tissue
      differences that enable or restrict abduction and external rotation at the
      anthropoid hip joint.

PMID- 24288180
TI  - Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase
      positive, advanced non-small cell lung cancer.
AB  - Crizotinib (Xalkori((r))) is an orally active, small molecule inhibitor of
      multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c
      Met/hepatocyte growth factor receptor and c-ros oncogene 1. In the EU, crizotinib
      has been conditionally approved for the treatment of adults with previously
      treated, ALK-positive, advanced non-small cell lung cancer (NSCLC). This approval
      has been based on objective response rate and tolerability data from two ongoing
      phase I/II studies (PROFILE 1001 and PROFILE 1005); these results have been
      substantiated and extended by findings from an ongoing phase III study (PROFILE
      1007) in patients with ALK-positive, advanced NSCLC who had received one prior
      platinum-based regimen. Those treated with crizotinib experienced significant
      improvements in progression-free survival, objective response rate, lung cancer
      symptoms and global quality of life, as compared with those treated with standard
      second-line chemotherapy (pemetrexed or docetaxel). The relative survival benefit
      with crizotinib is unclear, however, as the data are still immature and likely to
      be confounded by the high cross-over rate among chemotherapy recipients.
      Crizotinib treatment was generally well tolerated in the three PROFILE studies,
      with liver transaminase elevations and neutropenia being the most common grade 3
      or 4 adverse events. Crizotinib is the standard of care in terms of the treatment
      of patients with ALK-positive, advanced NSCLC; while the current EU approval is
      for second (or subsequent)-line use only, the first-line use of the drug is being
      evaluated in ongoing phase III studies. Key issues relating to the use of
      crizotinib in clinical practice include identifying the small subset of eligible
      patients, the almost inevitable development of resistance and the high cost of
      treatment. 

PMID- 24288181
TI  - In vivo monoubiquitination of anaplerotic phosphoenolpyruvate carboxylase occurs
      at Lys624 in germinating sorghum seeds.
AB  - Phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) is an important cytosolic
      regulatory enzyme that plays a pivotal role in numerous physiological processes
      in plants, including seed development and germination. Previous studies
      demonstrated the occurrence of immunoreactive PEPC polypeptides of ~110 kDa and
      107 kDa (p110 and p107, respectively) on immunoblots of clarified extracts of
      germinating sorghum (Sorghum bicolor) seeds. In order to establish the
      biochemical basis for this observation, a 460 kDa PEPC heterotetramer composed of
      an equivalent ratio of p110 and p107 subunits was purified to near homogeneity
      from the germinated seeds. Mass spectrometry established that p110 and p107 are
      both encoded by the same plant-type PEPC gene (CP21), but that p107 was in vivo
      monoubiquitinated at Lys624 to form p110. This residue is absolutely conserved in
      vascular plant PEPCs and is proximal to a PEP-binding/catalytic domain. Anti
      ubiquitin IgG immunodetected p110 but not p107, whereas incubation with a
      deubiquitinating enzyme (USP-2 core) efficiently converted p110 into p107, while
      relieving the enzyme's feedback inhibition by L-malate. Partial PEPC
      monoubiquitination was also detected during sorghum seed development. It is
      apparent that monoubiquitination at Lys624 is opposed to phosphorylation at Ser7
      in terms of regulating the catalytic activity of sorghum seed PEPC. PEPC
      monoubiquitination is hypothesized to fine-tune anaplerotic carbon flux according
      to the cell's immediate physiological requirements for tricarboxylic acid cycle
      intermediates needed in support of biosynthesis and carbon-nitrogen interactions.

PMID- 24288183
TI  - Silicon-oxygen double bonds: a stable silanone with a trigonal-planar coordinated
      silicon center.
AB  - Si?O in a complex: The first silanone that is stable at room temperature (3) is
      reported. The two-step synthesis involves carbonylation of the silylidyne complex
      1 to give the chromiosilylene 2, followed by oxidation of 2 with N2 O. Silanone 3
      features a polar, short Si?O bond (1.526(3) A) to a trigonal-planar-coordinated
      silicon center and reacts with water to give the dihydroxysilyl complex. 

PMID- 24288182
TI  - Dual regulation of cytosolic ascorbate peroxidase (APX) by tyrosine nitration and
      S-nitrosylation.
AB  - Post-translational modifications (PTMs) mediated by nitric oxide (NO)-derived
      molecules have become a new area of research, as they can modulate the function
      of target proteins. Proteomic data have shown that ascorbate peroxidase (APX) is
      one of the potential targets of PTMs mediated by NO-derived molecules. Using
      recombinant pea cytosolic APX, the impact of peroxynitrite (ONOO-) and S
      nitrosoglutathione (GSNO), which are known to mediate protein nitration and S
      nitrosylation processes, respectively, was analysed. While peroxynitrite inhibits
      APX activity, GSNO enhances its enzymatic activity. Mass spectrometric analysis
      of the nitrated APX enabled the determination that Tyr5 and Tyr235 were
      exclusively nitrated to 3-nitrotyrosine by peroxynitrite. Residue Cys32 was
      identified by the biotin switch method as S-nitrosylated. The location of these
      residues on the structure of pea APX reveals that Tyr235 is found at the bottom
      of the pocket where the haem group is enclosed, whereas Cys32 is at the ascorbate
      binding site. Pea plants grown under saline (150 mM NaCl) stress showed an
      enhancement of both APX activity and S-nitrosylated APX, as well as an increase
      of H2O2, NO, and S-nitrosothiol (SNO) content that can justify the induction of
      the APX activity. The results provide new insight into the molecular mechanism of
      the regulation of APX which can be both inactivated by irreversible nitration and
      activated by reversible S-nitrosylation.

PMID- 24288184
TI  - Polycaprolactone/oligomer compound scaffolds for cardiac tissue engineering.
AB  - Polycaprolactone (PCL), a synthetic biocompatible and biodegradable polymer
      generally used as a scaffold material for tissue engineering applications. The
      high stiffness and hydrophobicity of the PCL fiber mesh does not provide
      significant cell attachment and proliferation in cardiac tissue engineering.
      Towards this goal, the study focused on a compound of PCL and oligomer hydrogel
      [Bisphenol A ethoxylated dimethacrylate (BPAEDMA)] processed into electrospun
      nanofibrous scaffolds. The composition, morphology and mechanical properties of
      the compound scaffolds, composed of varying ratios of PCL and hydrogel were
      characterized by scanning electron microscopy, infrared spectroscopy and dynamic
      mechanical analyzer. The elastic modulus of PCL/BPAEDMA nanofibrous scaffolds was
      shown to be varying the BPAEDMA weight fraction and was decreased by increasing
      the BPAEDMA weight fraction. Compound fiber meshes containing 75 wt % BPAEDMA
      oligomer hydrogel exhibited lower modulus (3.55 MPa) and contact angle of 25(o) .
      Rabbit cardiac cells cultured for 10 days on these PCL/BPAEDMA compound
      nanofibrous scaffolds remained viable and expressed cardiac troponin and alpha
      actinin proteins for the normal functioning of myocardium. Cell adhesion and
      proliferations were significantly increased on compound fiber meshes containing
      75 wt % BPAEDMA, when compared with other nanofibrous scaffolds. The results
      observed that the produced PCL/BPAEDMA compound nanofibrous scaffolds promote
      cell adhesion, proliferation and normal functioning of cardiac cells to
      clinically beneficial levels, relevant for cardiac tissue engineering.

PMID- 24288185
TI  - DCX-expressing cells in the vicinity of the hypothalamic neurogenic niche: a
      comparative study between mouse, sheep, and human tissues.
AB  - Neural stem and precursor cells persist postnatally throughout adulthood and are
      capable of responding to numerous endogenous and exogenous signals by modifying
      their proliferation and differentiation. Whereas adult neurogenesis has been
      extensively studied in the dentate gyrus of the hippocampal formation and in the
      subventricular zone adjacent to the wall of the lateral ventricles, we and others
      have recently reported constitutive adult neurogenesis in other brain structures,
      including the hypothalamus. In this study, we used immunohistochemistry to study
      the expression of the neuroblast marker doublecortin (DCX), and compared its
      expression pattern in adult ovine, mouse, and human hypothalamic tissues. Our
      results indicate that DCX-positive cells resembling immature and developing
      neurons occur in a wide range of hypothalamic nuclei in all three species,
      although with different distribution patterns. In addition, the morphology of DCX
      positive cells varied depending on their location. DCX-positive cells near the
      third ventricle had the morphology of very immature neuroblasts, a round shape
      with no processes, whereas those located deeper in the parenchyma such as in the
      ventromedial nucleus were fusiform and showed a bipolar morphology. Extending
      this observation, we showed that among the cohort of immature neurons entering
      the ventromedial nucleus, some appeared to undergo maturation, as revealed by the
      partial colocalization of DCX with markers of more mature neurons, e.g., human
      neuronal protein C and D (HuC/D). This study provides further confirmation of the
      existence of an adult hypothalamic neurogenic niche and argues for the potential
      existence of a migratory path within the hypothalamus.

PMID- 24288187
TI  - The associations among dark personalities and sexual tactics across different
      scenarios.
AB  - Although malevolent individuals may be willing to use any tactic necessary to
      obtain sex, not all antagonistic traits will predict coercion or coaxing in all
      situations. A sample of 447 adult men, collected in two waves, reported their
      intentions to engage in coercion or coaxing of hypothetical targets. Study 1
      provided three hypothetical scenarios that result in sexual rejection: (a) an
      expensive date, (b) a stranger, and (c) a relationship partner, and Study 2
      provided the same scenarios, and three additional scenarios: (d) a rival's
      partner, (e) a bet, and (f) a powerful person. A Structural Equations Model
      indicated that a common antagonistic factor, indicated by Social Dominance and
      the Dark Triad traits of psychopathy, narcissism, and Machiavellianism, predicted
      coaxing across all situations, whereas only psychopathy predicted coercion across
      all situations. In addition, narcissism accounted for additional variance in
      coaxing when rejected by an expensive date. These findings suggest that across
      the different scenarios, psychopathy is primarily associated with coercive
      tactics and the common malevolent core among the traits is associated with
      coaxing tactics. 

PMID- 24288186
TI  - Detection of protein S-sulfhydration by a tag-switch technique.
AB  - Protein S-sulfhydration (forming -S-SH adducts from cysteine residues) is a newly
      defined oxidative posttranslational modification and plays an important role in
      H2 S-mediated signaling pathways. In this study we report the first selective,
      "tag-switch" method which can directly label protein S-sulfhydrated residues by
      forming stable thioether conjugates. Furthermore we demonstrate that H2 S alone
      cannot lead to S-sulfhydration and that the two possible physiological mechanisms
      include reaction with protein sulfenic acids (P-SOH) or the involvement of metal
      centers which would facilitate the oxidation of H2 S to HS(.) . 

PMID- 24288188
TI  - To tell or not to tell? factors influencing young people's informal disclosures
      of child sexual abuse.
AB  - The aim was to understand the factors influencing informal disclosure of child
      sexual abuse experiences, taking account of dynamics operating prior to, during,
      and following disclosure. In-depth semi-structured interviews were conducted with
      22 young people who experienced child sexual abuse and 14 parents. Grounded
      theory methodology informed the study. The key factors identified as influencing
      the disclosure process included being believed, being asked, shame/self-blame,
      concern for self and others, and peer influence. Many young people both wanted to
      tell and did not want to tell. Fear of not being believed; being asked questions
      about their well-being; feeling ashamed of what happened and blaming themselves
      for the abuse, for not telling, and for the consequences of disclosure; concern
      for how both disclosure and nondisclosure would impact on themselves and others;
      and being supported by and yet pressurized by peers to tell an adult, all
      illustrate the complex intrapersonal and interpersonal dynamics reflecting the
      conflict inherent in the disclosure process. These findings build on previous
      studies that emphasize the dialogic and interpersonal dynamics in the disclosure
      process. Both intrapersonal and interpersonal influencing factors need to be
      taken account of in designing interventions aimed at helping children tell. The
      importance of asking young people about their psychological well-being and the
      role of peer relationships are highlighted as key to how we can help young people
      tell. 

PMID- 24288189
TI  - Professionals' perceptions of support resources for battered immigrant women:
      chronicle of an anticipated failure.
AB  - The aim of this study was to explore the experience of service providers in Spain
      regarding their daily professional encounters with battered immigrant women and
      their perception of this group's help-seeking process and the eventual
      abandonment of the same. Twenty-nine in-depth interviews and four focus group
      discussions were conducted with a total of 43 professionals involved in providing
      support to battered immigrant women. We interviewed social workers,
      psychologists, intercultural mediators, judges, lawyers, and public health
      professionals from Spain. Through qualitative content analysis, four categories
      emerged: (a) frustration with the victim's decision to abandon the help-seeking
      process, (b) ambivalent positions regarding differences between immigrant and
      Spanish women, (c) difficulties in the migratory process that may hinder the help
      seeking process, and (d) criticisms regarding the inefficiency of existing
      resources. The four categories were cross-cut by an overarching theme: helping
      immigrant women not to abandon the help-seeking process as a chronicle of
      anticipated failure. The main reasons that emerged for abandoning the help
      seeking process involved structural factors such as economic dependence, loss of
      social support after leaving their country of origin, and limited knowledge about
      available resources. The professionals perceived their encounters with battered
      immigrant women to be frustrating and unproductive because they felt that they
      had few resources to back them up. They felt that despite the existence of public
      policies targeting intimate partner violence (IPV) and immigration in Spain, the
      resources dedicated to tackling gender-based violence were insufficient to meet
      battered immigrant women's needs. Professionals should be trained both in the
      problem of IPV and in providing support to the immigrant population. 

PMID- 24288190
TI  - Secondary traumatic stress and disruptions to interpersonal functioning among
      mental health therapists.
AB  - Disruptions within interpersonal relationships are often cited as a symptom of
      secondary traumatic stress (STS) and vicarious trauma among mental health
      therapists. However, the primary evidence to support these claims is based on
      theoretical explanations and limited descriptive data. The current study sought
      to test the theoretical model of STS and to extend prior research by directly
      measuring interpersonal and sexual disruptions and their association with STS
      symptomology. The study hypothesized that mental health therapists with higher
      levels of intrusion, avoidance, and arousal symptoms would also report
      disruptions in their interpersonal relationships. A total of 320 licensed mental
      health therapists completed the online study questionnaire. Results of the
      current study were mixed. Higher levels of STS symptoms showed a significant
      association with lower relationship satisfaction, lower social intimacy, less use
      of constructive communication patterns, and more use of avoidance communication
      and demand-withdrawal communication patterns. These relationships remained after
      controlling for gender, years of counseling experience, and exposure level to
      trauma clients. However, no association was found between STS, sexual activity
      interest, and sexual relationship satisfaction. Implications of these findings
      are reviewed. 

PMID- 24288192
TI  - Consequences of intimate partner violence against women on under-five child
      mortality in Bangladesh.
AB  - It is well established that intimate partner violence (IPV) against women
      adversely affects maternal morbidity and mortality. But a limited number of
      studies were found in the literature regarding the association between IPV and
      under-five child mortality. In this article, using Bangladesh Demographic and
      Health Survey (BDHS) 2007 data, we examined the effect of IPV on under-five child
      mortality. A product-limit approach was used for bivariate survival analysis, and
      Cox proportional hazard multiple regression models were used to investigate the
      effect of IPV controlling potential confounders. In bivariate analysis, the
      variables exposure to IPV, mother's age at birth, mother's education, residence
      type, division, number of children, wealth index, occupation, access to media,
      and decision autonomy were found to be potential risk factors for child
      mortality. Results indicated that women exposed to IPV were more likely to
      experience under-five child mortality compared with women not exposed. The
      unadjusted hazard ratio for IPV was 1.21 (95% confidence interval [CI] = [1.09,
      1.35]) with p value < .01, whereas it was 1.16 (95% CI = [1.04, 1.29]) with p
      value < .01 and 1.13 (95% CI = [1.01, 1.26]) with p value < .05 in two adjusted
      models. These results implied that IPV against women is a problem not only for
      women but also for their children's survival. 

PMID- 24288191
TI  - The relationship between assault and physical health complaints in a sample of
      female drinkers: roles of avoidant coping and alcohol use.
AB  - Trauma exposure and PTSD are associated with poorer physical health.
      Psychological and behavioral mechanisms may help account for this relationship.
      In this study, we tested avoidant coping and alcohol use as mediators of the
      relationship between trauma exposure, PTSD, and self-reported physical health
      complaints in female drinkers. In 827 college women, we compared three groups:
      women with no trauma history, women with a sexual assault but no PTSD, and women
      with a sexual assault and PTSD, on avoidant coping, alcohol use, and physical
      health complaints. We found that PTSD was positively associated with alcohol use
      and that PTSD and trauma exposure were associated with increased avoidant coping.
      We also found that avoidant coping mediated the relationship between trauma,
      PTSD, and physical health complaints. Alcohol use did not predict physical health
      but was associated with PTSD. These results suggest that in female college
      students, coping may be more critical in the PTSD/physical health relationship
      than alcohol and have implications for targeting coping in young trauma-exposed
      women to improve physical health. 

PMID- 24288193
TI  - Religiosity and violence among adolescents in the United States: findings from
      the national survey on drug use and health 2006-2010.
AB  - There is a pressing need to develop a more nuanced understanding of the
      relationships between particular expressions of religiosity and the various
      manifestations of violence among youth. This study examines these relationships
      among adolescents in the general population as well as across racial/ethnic,
      gender, and family income differences. Using a nationally representative sample
      of adolescents (N = 90,202) from the National Survey on Drug Use and Health (2006
      2010), logistic regression is used to examine the relationships between
      religiosity and violence. Results indicate that multiple components of adolescent
      religiosity are associated with the decreased likelihood of fighting, group
      fighting, and, to a lesser extent, violent attacks. A number of noteworthy
      differences were identified across race/ethnicity, gender, and family income.
      Findings from this investigation shed light on the relationship between
      particular facets of religiosity and violence that may be useful for violence
      prevention organizations seeking to integrate religious components into
      intervention efforts. 

PMID- 24288194
TI  - Can anisotropic exchange be reliably calculated using density functional methods?
      A case study on trinuclear Mn(III)-M(III)-Mn(III) (M=Fe, Ru, and Os)
      cyanometalate single-molecule magnets.
AB  - Density functional studies have been performed on a set of trinuclear single
      molecule magnets (SMMs) of general formula [{Mn2(5-Br
      salen)2(MeOH)2}M(CN)6](NEt4) (M=Fe(III) (1), Ru(III) (2) and Os(III) (3); 5
      Brsalen=N,N'-ethylenebis(5-bromosalicylidene)iminato anion). We have computed the
      orbital-dependent exchange interaction for all three complexes for the first time
      using DFT and complete active space self-consistent field (CASSCF) methods. DFT
      calculations yield the anisotropic exchange as J(xixi)=3.5 cm(-1) for 1;
      J(xixi)=12.1 cm(-1), J(zetazeta)=-6.9 cm(-1) and J(etaeta)=-14 cm(-1) for 2; and
      J(xixi)=23.7 cm(-1) and J(zetazeta) =-11.1 cm(-1) for 3. The computed values are
      in agreement with the experimental report, and this suggests that the established
      methodology can be used to compute the anisotropic exchange in larger clusters.
      Our calculations reiterate the fact that the exchange is described by a three
      axis anisotropic exchange for complexes 2 and 3 as evidenced by the experiments.
      A stronger exchange coupling as we move down the periodic table from 3d to 5d is
      reproduced by our calculations, and the origin of this enhancement in the
      exchange interaction has been probed by using molecular orbital analysis. The
      electronic origin of different types of exchange observed in this series is found
      to be related to the energy difference between possible degenerate pairs and the
      nature of orbital interactions. By computing the exchange interaction, the single
      ion anisotropy of Mn(III) and zero-field splitting of the S=9/2 ground state of
      complexes 1-3 using CASSCF and/or DFT methods, we have attempted to shed light on
      the issue of anisotropic exchange and the barrier height for the magnetisation
      reversal in SMMs. Comprehensive magneto-structural correlations have been
      developed to offer clues on how to further enhance the barrier height in this
      class of SMMs.

PMID- 24288197
TI  - Catheter-related urinary tract infection: practical management in the elderly.
AB  - From 5-10% of elderly residents of long-term care facilities require chronic
      indwelling catheters for management of urine voiding. These residents are always
      bacteriuric, because of biofilm formation along the catheter, and experience
      increased morbidity associated with urinary tract infection. A wide variety of
      bacteria or yeast species are isolated. Occasional episodes of symptomatic
      infection may be accompanied by localizing genitourinary findings. However, when
      fever is present and there are no localizing findings, symptomatic infection is a
      diagnosis of exclusion. Many of these episodes are not from a urinary source, so
      critical clinical evaluation is always necessary. A urine specimen for culture
      should be obtained from patients with symptomatic infection prior to institution
      of antimicrobial therapy. When the catheter has been present for 2 weeks or
      longer, it should be replaced and the urine specimen collected through the new
      catheter. This provides a specimen of bladder urine without biofilm
      contamination, and catheter replacement also improves clinical outcomes.
      Treatment algorithms with a goal of limiting inappropriate treatment of
      asymptomatic bacteriuria have been developed. Empiric antimicrobial therapy
      should be avoided when possible. Guidelines for prevention of catheter-acquired
      urinary infection should be followed. The most important of these is to avoid use
      of a urinary catheter whenever possible and, when there is no longer an
      indication for the catheter, to remove it promptly.

PMID- 24288198
TI  - Cytoplasmic PML: from molecular regulation to biological functions.
AB  - The tumor suppressor promyelocytic leukemia protein (PML) is predominantly
      localized in the nucleus, where it is essential for the formation and
      stabilization of the PML nuclear bodies (PML-NBs). PML-NBs are involved in the
      regulation of numerous cellular functions, such as tumorigenesis, DNA damage and
      antiviral responses. Despite its nuclear localization, a small portion of PML has
      been found in the cytoplasm. A number of studies recently demonstrated that the
      cytoplasmic PML (cPML) has diverse functions in many cellular processes including
      tumorigenesis, metabolism, antiviral responses, cell cycle regulation, and
      laminopothies. In this prospective, we will summarize the current viewpoints on
      the regulation and biological significance of cPML and discuss the important
      questions that still need to be further answered.

PMID- 24288199
TI  - Inhibition of rhBMP-2-induced ALP activity by intracellular delivery of SMURF1 in
      murine calvarial preosteoblast cells.
AB  - Intracellular protein delivery is a novel tool for functional analysis of protein
      inside a cell. Several protein delivery reagents with diverse mechanisms have
      been developed and are commercially available. In this study, we focused on the
      inhibitory effect of intracellular delivery of SMAD ubiquitination regulation
      factor 1 (SMURF1) on the recombinant human bone morphogenetic protein-2 (rhBMP-2)
      signaling pathway. First, three commercially available reagents for intracellular
      delivery (BioPORTER((r)), PULSin((r)), and Xfect(TM)) were tested in a murine
      preosteoblast cell line, MC3T3-E1.4. The biocompatibility of these reagents was
      examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium assay and the cellular uptake and delivery efficiency
      were determined with FITC-antibody and beta-galactosidase (beta-gal),
      respectively. BioPORTER((r)) provided the best results and was, therefore, chosen
      for the second aspect of our study: intracellular SMURF1 delivery.
      SMURF1/BioPORTER((r)) complexes were applied to cells prior to rhBMP-2
      application. The outcome data suggest intracellular SMURF1 delivery in MC3T3-E1.4
      cells significantly inhibited alkaline phosphatase upregulation. This outcome may
      be useful to off-targets effects of rhBMP-2.

PMID- 24288200
TI  - Total synthesis of pectenotoxin-2.
AB  - Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal,
      which is not stabilized by an anomeric effect. The selective construction of the
      non-anomeric spiroacetal has been a major problem in the synthesis of PTX2.
      Described herein is the stereoselective total synthesis of PTX2 via the
      isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of
      PTX2b was achieved by a simple process including sulfone-mediated assembly of
      spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing
      olefin metathesis. Finally, the selective construction of PTX2 was accomplished
      by the early termination of a dynamic transition process to equilibrium in the
      acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c
      (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic
      compounds against HepG2 and Caco2 cancer cells showed a potency of the order:
      PTX2?PTX2b>PTX2c.

PMID- 24288201
TI  - Brief, personality-targeted, teacher-delivered CBT interventions reduce
      depression, anxiety and conduct disorder symptoms in high-risk adolescents.

PMID- 24288202
TI  - Review: one in seven homicides worldwide is perpetrated by an intimate partner.

PMID- 24288203
TI  - Evaluation of capecitabine and oxaliplatin administered prior to and then
      concomitant to radiotherapy in high risk locally advanced rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Systemic failure remains a predominant issue in
      locally advanced rectal cancer (LARC). A new strategy using capecitabine and
      oxaliplatin (XELOX regimen) administered prior to and then concomitant to
      radiotherapy for high risk LARC is developed in our practice. The aim of the
      present study was to evaluate the short-term efficacy and toxicities of this
      strategy. METHODS: Patients were treated with one cycle XELOX regimen
      (oxaliplatin 130 mg/m(2) on day 1 with capecitabine 1,000 mg/m(2) twice daily for
      14 days every 3 weeks), followed by chemoradiation (50 Gy over 5 weeks) with
      modified XELOX regimen (oxaliplatin dose reduction to 100 mg/m(2)), and total
      mesorectal excision. Tumor response, toxicities, and surgical complications were
      recorded. RESULTS: Forty-two patients treated with the strategy were identified.
      All patients completed planned dose of induction chemotherapy and concurrent
      chemoradiotherapy. Grade 3 toxicities were thrombocytopenia (4.8%), diarrhea
      (7.1%), proctitis (4.8%), and radiation dermatitis (7.1%). Five patients (12.5%)
      developed postoperative complications. Pathologic complete response (pCR) and
      nearly pCR were achieved in 7 (15.0%) and 13 patients (35.0%). CONCLUSIONS: The
      preliminary results suggest that induction chemotherapy followed by
      chemoradiotherapy with capecitabine and oxaliplatin in LARC is well tolerated.
      The strategy achieves favorable short term outcome in terms of pCR and nearly pCR
      rate, which warrants further investigation.

PMID- 24288204
TI  - Synthesis of highly pH-responsive glucose poly(orthoester).
AB  - pH-Responsive polymers have great potential in biomedical applications, including
      the selective delivery of preloaded drugs to tissues with low pH values. These
      polymers usually contain acid-labile linkages such as esters and acetals/ketals.
      However, these linkages are only mildly pH-responsive with relatively long half
      lives (t1/2 ). Orthoester linkages are more acid-labile, but current methods
      suffer from synthetic challenges and are limited to the availability of monomers.
      To address these limitations, a sugar poly(orthoester) was synthesized as a
      highly pH-responsive polymer. The synthesis was achieved by using 2,3,4-tri-O
      acetyl-alpha-D-glucopyranosyl bromide as a difunctional AB monomer and tetra-n
      butylammonium iodide (TBAI) as an effective promoter. Under optimal conditions,
      polymers with molecular weights of 6.9 kDa were synthesized in a polycondensation
      manner. The synthesized glucose poly(orthoester), wherein all sugar units were
      connected through orthoester linkages, was highly pH-responsive with a half-life
      of 0.9, 0.6, and 0.2 hours at pH 6, 5, and 4, respectively. 

PMID- 24288205
TI  - Asymmetric alpha-hydroxylation of a lactone with vinylogous pyridone by using a
      guanidine-urea bifunctional organocatalyst: catalytic enantioselective synthesis
      of a key intermediate for (20S)-camptothecin analogues.
AB  - We have developed a catalytic asymmetric synthesis of (S)-4-ethyl-6,6
      (ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,10(4H)dione (5
      a), a synthetic intermediate for (20S)-camptothecin analogues. A key step in this
      synthesis is an asymmetric alpha-hydroxylation of a lactone with a vinylogous
      pyridone structure (8 a) by using a guanidine-urea bifunctional organocatalyst.
      The present oxidation was successfully applied to the synthesis of C20-modified
      derivatives of (+)-C20-desethylbenzylcamptothecin (13). 

PMID- 24288206
TI  - In situ facile synthesis of Ru-based core-shell nanoparticles supported on carbon
      black and their high catalytic activity in the dehydrogenation of amine-boranes.
AB  - Well-dispersed core-shell Ru@M (M=Co, Ni, Fe) nanoparticles (NPs) supported on
      carbon black have been synthesized via a facile in situ one-step procedure under
      ambient condition. Core-shell Ru@Co NPs were synthesized and characterized for
      the first time. The as-synthesized Ru@Co and Ru@Ni NPs exhibit superior catalytic
      activity in the hydrolysis of ammonia borane compared with their monometallic and
      alloy counterparts. The Ru@Co/C NPs are the most reactive, with a turnover
      frequency (TOF) value of 320 (mol H 2 min(-1)) molRu (-1) and activation energy
      (Ea) of 21.16 kJ mol(-1). Ru@Ni/C NPs are the next most active, whereas Ru@Fe/C
      NPs are almost inactive. Additionally, the as-synthesized NPs supported on carbon
      black exhibit higher catalytic activity than catalysts on other conventional
      supports, such as SiO2 and gamma-Al2O3.

PMID- 24288207
TI  - Cost effectiveness of the new pneumococcal vaccines: a systematic review of
      European studies.
AB  - INTRODUCTION: Diseases caused by Streptococcus pneumoniae (pneumococcus) are a
      major global public health problem. Despite their importance, information on the
      burden of the different pneumococcal diseases is limited and estimates vary
      widely. OBJECTIVE AND METHODS: We critically reviewed the full economic
      evaluations (FEEs) on the new pneumococcal conjugate vaccines (PCVs) conducted in
      the European Union (EU) to assess their potential contribution to public decision
      making. We selected the FEEs focussed on PCV-10 and PCV-13 and published in
      English from January 2007 until June 2013. We screened the selected articles to
      assess their main methodological features using a common checklist composed of
      epidemiological, clinical and economic items. RESULTS: All the ten studies
      selected were based on modelling and the time horizon was always long term. Two
      studies focused on adults, the remaining eight on infants. Only one study based
      herd immunity on national data, eight used foreign data or modelling and the last
      did not consider it. National prices and tariffs were claimed to be sources for
      unit costs in all studies; however, half of them assumed price parity when one
      vaccine was not yet marketed, and the figures varied within the countries where
      more than one study was conducted. Conclusions supported the economic utility of
      pneumococcal vaccination in all studies, raising some concern only in (i) the
      independent study, which found that PCV-13 was borderline cost effective, and
      (ii) the study sponsored by both manufacturers, which estimated an incremental
      ratio slightly above the national threshold for both PCV-10 and PCV-13.
      CONCLUSION: The European studies we analysed are mostly based on weak sources of
      data. Because of the limited information on vaccine effectiveness and lack of
      epidemiological and economic data, the need for extensive recourse to assumptions
      leads to great within- and between-study variability generated by authors'
      choices.

PMID- 24288209
TI  - Why should regulators consider using patient preferences in benefit-risk
      assessment?

PMID- 24288208
TI  - Cost effectiveness of a 21-gene recurrence score assay versus Canadian clinical
      practice in post-menopausal women with early-stage estrogen or progesterone
      receptor-positive, axillary lymph-node positive breast cancer.
AB  - BACKGROUND: A 21-gene recurrence score (RS) assay provides a method of guiding
      treatment decisions in women with early-stage breast cancer (ESBC). We
      investigated the cost effectiveness of using the RS assay versus current clinical
      practice (CCP) in post-menopausal women with estrogen- or progesterone-receptor
      positive, one to three positive axillary lymph-node ESBC from the perspective of
      the Canadian public healthcare system. METHODS: We developed a decision analytic
      model to project the lifetime clinical and economic consequences of ESBC. We
      assumed that the RS assay would classify patients among risk levels (low,
      intermediate and high) and corresponding adjuvant treatment regimens. The model
      was parameterized using 7-year follow-up data from the Manitoba Cancer Registry,
      cost data from Manitoba Health administrative databases and secondary sources.
      Costs are presented in 2012 Canadian dollars, and future costs and benefits were
      discounted at 5 %. RESULTS: In the base case analysis, the RS assay compared with
      CCP led to an increase of 0.08 quality-adjusted life-year (QALY) and an increase
      in cost of Can$36.2 per person, resulting in an incremental cost-effectiveness
      ratio (ICER) of Can$464/QALY gained. The ICER was most sensitive to the
      proportion of women classified to intermediate risk by the RS assay who received
      adjuvant chemotherapy, and absolute risk of relapse among patients receiving the
      RS assay. CONCLUSIONS: The RS assay is likely to be cost effective in the
      Canadian healthcare system. Field evaluations of the assay in this patient
      population will help reduce uncertainty in clinical guidelines for intermediate
      range RS-assay values and specific disease outcomes by the RS assay, which are
      important drivers of ICER.

PMID- 24288210
TI  - Scaffolding for challenging environments: materials selection for tissue
      engineered intestine.
AB  - Novel therapies are crucially needed for short bowel syndrome. One potential
      therapy is the production of tissue engineered intestine (TEI). The intestinal
      environment presents significant challenges to the selection of appropriate
      material for tissue engineering scaffolds. Our goal was to characterize different
      scaffold materials to downselect to that best suited for TEI production. To
      investigate this, various tubular scaffolds were implanted into the peritoneal
      cavity of adult rats and harvested at multiple time-points. Harvested scaffolds
      were examined histologically and subjected to degradation studies and mechanical
      evaluation. We found that poly(glycolic acid) (PGA)-nanofiber and PGA-macrofiber
      scaffolds exhibited early robust tissue infiltration. Poly(E-caprolactone) (PCL)
      nanofiber, poly(l-lactic acid) (PLLA)-nanofiber, poly(d-lactic acid-co-glycolic
      acid) (PDLGA)-nanofiber and polyurethane (PU)-nanofiber experienced slower tissue
      infiltration. Poly(E-caprolactone-co-lactic acid) (PLC) nanofiber had poor tissue
      infiltration. Significant weight loss was observed in PGA-nanofiber (92.2%), PGA
      macrofiber (67.6%), and PDLGA-nanofiber (76.9%) scaffolds. Individual fibers were
      no longer seen by scanning electron microscopy in PLC-nanofiber and PGA-nanofiber
      scaffolds after 1 week, PGA-macrofiber scaffolds after 2 weeks, and PDLGA
      nanofiber scaffolds after 4 weeks. In conclusion, PGA-macrofiber and PDLGA appear
      to be the most appropriate materials choices as TEI scaffolds due to their
      biocompatibility and degradation. Future experiments will confirm these results
      by analyzing cell-seeded scaffolds in vitro and in vivo.

PMID- 24288212
TI  - "Batch" kinetics in flow: online IR analysis and continuous control.
AB  - Currently, kinetic data is either collected under steady-state conditions in flow
      or by generating time-series data in batch. Batch experiments are generally
      considered to be more suitable for the generation of kinetic data because of the
      ability to collect data from many time points in a single experiment. Now, a
      method that rapidly generates time-series reaction data from flow reactors by
      continuously manipulating the flow rate and reaction temperature has been
      developed. This approach makes use of inline IR analysis and an automated
      microreactor system, which allowed for rapid and tight control of the operating
      conditions. The conversion/residence time profiles at several temperatures were
      used to fit parameters to a kinetic model. This method requires significantly
      less time and a smaller amount of starting material compared to one-at-a-time
      flow experiments, and thus allows for the rapid generation of kinetic data. 

PMID- 24288211
TI  - CCN2 as a novel molecule supporting energy metabolism of chondrocytes.
AB  - CCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes
      both chondrocytic differentiation and proliferation through its matricellular
      interaction with a number of extracellular biomolecules. This apparently
      contradictory functional property of CCN2 suggests its certain role in basic
      cellular activities such as energy metabolism, which is required for both
      proliferation and differentiation. Comparative metabolomic analysis of costal
      chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired
      metabolism in the latter. Among the numerous metabolites analyzed, stable
      reduction in the intracellular level of ATP, GTP, CTP, or UTP was observed,
      indicating a profound role of CCN2 in energy metabolism. Particularly, the
      cellular level of ATP was decreased by more than 50% in the Ccn2-null
      chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured Ccn2-null
      chondrocytes partly redeemed the cellular ATP level attenuated by Ccn2 deletion.
      Next, in order to investigate the mechanistic background that mediates the
      reduction in ATP level in these Ccn2-null chondrocytes, we performed
      transcriptome analysis. As a result, several metabolism-associated genes were
      found to have been up-regulated or down-regulated in the mutant mice. Up
      regulation of a number of ribosomal protein genes was observed upon Ccn2
      deletion, whereas a few genes required for aerobic and anaerobic ATP production
      were down-regulated in the Ccn2-null chondrocytes. Among such genes, reduction in
      the expression of the enolase 1 gene was of particular note. These findings
      uncover a novel functional role of CCN2 as a metabolic supporter in the growth
      plate chondrocytes, which is required for skeletogenesis in mammals.

PMID- 24288214
TI  - Catalytic ammonia synthesis in homogeneous solution--biomimetic at last?

PMID- 24288213
TI  - Introducing advanced clinical reasoning to an adult learning disability service.
AB  - The advanced clinical reasoning approach is widely adopted in speech and language
      therapy practice. This article reports on the introduction of the approach across
      a multidisciplinary adult learning disability service and staff reports on the
      impact of this initiative. Staff in the service were offered training in the
      approach. Staff completed pre-course questionnaires, immediate post-course
      evaluations of the training and questionnaires a year after initial training.
      Semi-structured interviews took place with three team managers a year after the
      training. Staff and team managers reported that the training had a positive
      impact on their practice. All respondents demonstrated confidence in the use of
      the advanced clinical reasoning terminology and a clear understanding of the
      nature of duty of care and clinical risk. Enhanced knowledge about caseloads and
      greater confidence in managing episodes of care were reported by staff and team
      managers to have resulted in a more efficient and effective service. 

PMID- 24288215
TI  - Computer vision-based analysis of foods: a non-destructive colour measurement
      tool to monitor quality and safety.
AB  - Computer vision-based image analysis has been widely used in food industry to
      monitor food quality. It allows low-cost and non-contact measurements of colour
      to be performed. In this paper, two computer vision-based image analysis
      approaches are discussed to extract mean colour or featured colour information
      from the digital images of foods. These types of information may be of particular
      importance as colour indicates certain chemical changes or physical properties in
      foods. As exemplified here, the mean CIE a* value or browning ratio determined by
      means of computer vision-based image analysis algorithms can be correlated with
      acrylamide content of potato chips or cookies. Or, porosity index as an important
      physical property of breadcrumb can be calculated easily. In this respect,
      computer vision-based image analysis provides a useful tool for automatic
      inspection of food products in a manufacturing line, and it can be actively
      involved in the decision-making process where rapid quality/safety evaluation is
      needed.

PMID- 24288216
TI  - Improved glucose-neopentyl glycol (GNG) amphiphiles for membrane protein
      solubilization and stabilization.
AB  - Membrane proteins are inherently amphipathic and undergo dynamic conformational
      changes for proper function within native membranes. Maintaining the functional
      structures of these biomacromolecules in aqueous media is necessary for
      structural studies but difficult to achieve with currently available tools, thus
      necessitating the development of novel agents with favorable properties. This
      study introduces several new glucose-neopentyl glycol (GNG) amphiphiles and
      reveals some agents that display favorable behaviors for the solubilization and
      stabilization of a large, multi-subunit membrane protein assembly. Furthermore, a
      detergent structure-property relationship that could serve as a useful guideline
      for the design of novel amphiphiles is discussed. 

PMID- 24288217
TI  - Rhodium-catalyzed directed sulfenylation of arene C-H bonds.
AB  - The rhodium-catalyzed intermolecular direct C-H thiolation of arenes with aryl
      and alkyl disulfides was developed for the first time to provide a convenient
      route to aryl thioethers. This strategy is compatible with many different
      directing groups and exhibits excellent functional group tolerance. More
      significantly, mono- or dithiolation can be selectively achieved, thus providing
      a straightforward way for selective preparation of aryl thioethers and
      dithioethers.

PMID- 24288218
TI  - The field effect in Barrett's esophagus: can we use it for screening and
      surveillance?

PMID- 24288219
TI  - Long-term outcome of endoscopic resection of superficial adenocarcinoma of the
      esophagogastric junction.
AB  - BACKGROUND AND STUDY AIM: Endoscopic resection has been favored for the
      management of intramucosal adenocarcinoma of the esophagogastric junction (AEGJ)
      over standard treatment with surgical resection. Several previous studies have
      reported only short-term outcomes. The aim of the present study was to report the
      long-term follow-up and outcomes of endoscopic submucosal dissection (ESD), a
      representative endoscopic resection method, for the management of superficial
      AEGJ. PATIENTS AND METHODS: A retrospective cohort study included 53 consecutive
      patients with superficial AEGJ who underwent ESD between 2001 and 2007 at the
      National Cancer Center Hospital, Tokyo, Japan. Rates of overall survival,
      recurrence-free survival, and cause-specific survival of patients with AEGJ after
      endoscopic resection were analyzed. RESULTS: The 5-year overall, recurrence-free,
      and cause-specific survival rates in the 53 patients were 94.2%, 92.3% and 96.1%,
      respectively. The median follow-up was 6.1 years. En bloc, R0, and curative
      resection rates were 100 %, 79 %, 68 %, respectively. In 36 patients with
      curative resection, the cause-specific survival rate was 100 % and no recurrence
      or metastases were detected. In 17 patients with non-curative resection,
      recurrence was found in three patients (17 %); two of the three patients died of
      their disease whilst one patient received chemotherapy. CONCLUSIONS: Superficial
      AEGJ can be well controlled by ESD when curative resection is achieved.

PMID- 24288220
TI  - In vitro evaluation of the radial and axial force of self-expanding esophageal
      stents.
AB  - BACKGROUND AND STUDY AIMS: Technological innovation in esophageal stent design
      has progressed over the past decades, but the association between the mechanical
      properties of stent design and clinical outcome is still poorly understood. In
      this study the radial force and axial force of currently available stent designs
      were evaluated using an in vitro testing model. METHODS: A total of 10 partially
      and fully covered self-expanding metal stents (SEMSs), a self-expanding plastic
      stent (SEPS), and an uncovered biodegradable stent were evaluated. Radial force
      and axial force were measured using a radial force measurement machine (RX500)
      and a force gauge in an oven at 37 degrees C. RESULTS: A wide range of radial
      force measurements were observed between the different stent designs, ranging
      from 4 to 83 N at 15  mm expansion. All braided nitinol stents displayed
      comparable mechanical characteristics with a relatively low radial force (<150 N)
      that gradually decreased to 0 N during expansion, whereas plastic and metal
      stents that were constructed in a nonbraided manner displayed an initially high
      radial force (>300 N) followed by a steep decline to 0 N during expansion.
      Conversely, peak axial force was relatively high for braided nitinol SEMSs (>1.5
      N), whereas nonbraided SEMSs showed a much lower peak axial force (<1.5 N). Based
      on radial and axial force data, five groups of stents with comparable mechanical
      properties could be distinguished. CONCLUSIONS: All currently available stents
      have a characteristic radial and axial force pattern, which may aid in the
      understanding of the occurrence of specific symptoms and complications after
      stent placement. Nonetheless, the overall clinical behavior of a stent is
      probably more complex and cannot be explained by these factors alone.

PMID- 24288221
TI  - Endoscopic plastic stenting for bile duct stones: stent changing on demand or
      every 3 months. A prospective comparison study.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biliary sphincterotomy and stone removal is
      the standard of care for choledocholithiasis, with a success rate of > 90%. For
      stones <= 25 mm diameter, mechanical lithotripsy, extracorporeal shock wave
      lithotripsy, electrohydraulic lithotripsy, and laser lithotripsy can be used. In
      the case of failure, the next step is surgery. In elderly patients and in
      patients with an elevated surgical risk, stenting is the only treatment modality.
      In these cases the aim is to avoid the onset of acute obstructive cholangitis.
      The aim of the current study was to evaluate the best management of plastic
      stents in patients with biliary duct stones who were unfit for surgery and in
      whom previous endoscopic therapy had failed. METHODS: Patients who were high
      surgical risks and in whom stone clearance was not possible due to the number and
      sizes of stones were included. Between March 2008 and September 2010 all patients
      were treated with endoscopic plastic biliary stenting at four tertiary care
      referral centers in Italy. Patients were randomly assigned to two groups: in
      Group A (n=39) plastic stents were changed every 3 months or sooner if symptoms
      appeared; in Group B plastic stents were changed on demand at the onset of
      symptoms, and ultrasonography and blood samples were performed every 3 months to
      check for signs of cholestasis and inflammation. The primary outcome was the rate
      of cholangitis. The secondary outcome was the rate of stone clearance after a
      period of stenting. RESULTS: A total of 78 patients were included in the study
      (43 M/35F; mean age 76 years). Acute cholangitis occurred in 3 patients from
      Group A and in 14 patients from Group B (P=0.03). Mortality related to
      cholangitis occurred in one patient from Group A and three patients from Group B
      (P=n.s.). The mean follow-up was 13.5 months (range 2-23). Stone clearance after
      long term stenting occurred in 24 patients from Group A (61.5 %) and in 21
      patients from group B (53.8%) (P=n.s.). CONCLUSIONS: In patients with bile duct
      stones who were treated with biliary plastic stents, the best stent management to
      avoid cholangitis was stent changing at defined intervals (every 3 months in the
      current study). The data confirmed that plastic biliary stenting may decrease
      stone size with a high percentage of subsequent total stone clearance.

PMID- 24288222
TI  - Clinical outcomes of rectal neuroendocrine tumors <= 10 mm following endoscopic
      resection.
AB  - BACKGROUND AND STUDY AIMS: This study was conducted to determine the clinical
      outcome of rectal neuroendocrine tumors (NETs)<= 10 mm following conventional
      endoscopic resection. PATIENTS AND METHODS: A total of 107 patients who underwent
      conventional endoscopic treatment for rectal NETs (median size 5.0 mm [range 1.0
      10.0]) were followed up for a median of 31 months (range 13-121). The following
      data were analyzed: lesion characteristics, clinical outcomes, and histological
      features determined using tissue microarray analysis (TMA), including the mitotic
      count and the Ki-67 index. RESULTS: En bloc removal was achieved for all tumors,
      and the complete resection rate was 49.5% (53/107). Resection margin status was
      indeterminate in 37 patients (34.6%) and positive in 17 (15.9%). Rectal NETs in
      71 patients demonstrated a score of <=2 % on the Ki-67 index and<2 for mitotic
      count on TMA. In another 28 tumors that did not undergo TMA, the mitotic count
      was 0-1 per 10 high-power fields. Neither recurrence nor metastasis was noted
      during the follow-up period following resection. CONCLUSIONS: Rectal NETs (<=10
      mm in size) appear to demonstrate benign behavior based on the mitotic count and
      the Ki-67 index. These results suggest that the outcome of rectal NETs (<=10 mm
      in size) following conventional endoscopic resection might be comparatively
      excellent, regardless of the resection margin status. However, long term follow
      up data are required to confirm this.

PMID- 24288223
TI  - Polyp resection - lessons learned.

PMID- 24288224
TI  - UEG Week 2013 highlights: putting endoscopy into perspective.
AB  - The 21st United European Gastroenterology (UEG) Week was held in Berlin in
      October 2013 and presented the opportunity for those interested in
      gastrointestinal endoscopy to learn of recent developments and research trends
      from all over the world. This report highlights oral presentations of the most
      important and exciting topics in gastrointestinal endoscopy and reviews them in
      the context of current knowledge. 

PMID- 24288225
TI  - Prevalence of flat lesions in a large screening population and their role in
      colonoscopy quality improvement.

PMID- 24288226
TI  - Reply to Chiu et al. And Lasa et al.

PMID- 24288227
TI  - Flat lesion detection as a surrogate for colonoscopy quality.

PMID- 24288229
TI  - Liquid crystal chemical sensors that cells can wear.

PMID- 24288230
TI  - Total synthesis of (+/-)-gephyrotoxin by amide-selective reductive nucleophilic
      addition.
AB  - A chemoselective approach for the total synthesis of (+/-)-gephyrotoxin has been
      developed. The key to success was the utilization of N-methoxyamides, which
      enabled the direct coupling of the amide with an aldehyde and selective reductive
      nucleophilic addition to the amide in the presence of a variety of sensitive and
      electrophilic functional groups, such as a methyl ester. This chemoselective
      approach minimized the use of protecting-group manipulations and redox reactions,
      which resulted in the most concise and efficient total synthesis of (+/-)
      gephyrotoxin described to date. 

PMID- 24288231
TI  - Impact of imidacloprid on Daphnia magna under different food quality regimes.
AB  - Aquatic ecosystems are characterized by fluctuating conditions that have direct
      effects on aquatic communities but also indirect influences such as changing the
      toxicity of chemicals. Because the effect of food quality on pesticide toxicity
      has rarely been studied, in the present study Daphnia magna juveniles supplied
      with 4 different food quality levels were exposed to a range of imidacloprid
      concentrations for 21 d. Food quality was expressed as carbon:phosphorus ratios
      of algae Pseudokirchneriella subcapitata (C:P 35, C:P 240, C:P 400, and C:P
      1300). Survival, growth rates, and reproduction of D. magna were monitored, and
      the combined effects of imidacloprid exposure and the phosphorus content of algae
      were analyzed. A stronger effect on survival was observed at the P-deficient diet
      (C:P 1300), confirmed by lower 10% effect concentration (EC10) values at days 7,
      9, 15, and 21 compared with diets with higher phosphorus contents. Similarly, the
      growth rate was reduced when D. magna were supplied with algae of low phosphorus
      content at imidacloprid exposure conditions. The highest reproductive output was
      observed for D. magna fed the optimal phosphorus diet (C:P 240), both at control
      and exposed conditions. Poor food quality increased the sensitivity of nontarget
      species to pesticide exposure, potentially leading to an underestimation of
      adverse effects on aquatic communities in the field.

PMID- 24288232
TI  - Amine-catalyzed direct photoarylation of unactivated arenes.
AB  - Constructing biaryls through direct aromatic C-H functionalization of unactivated
      arenes has become a popular topic in organic chemistry. Many efficient methods
      have been developed. In this Communication, a direct arylation of unactivated
      arenes with a broad range of aryl iodides is reported. This reaction proceeds
      through a new type of amine-catalyzed single electron transfer initiated radical
      coupling procedure to form biaryls in high yields under UV irradiation at room
      temperature. Only 20 mol% of TMEDA is used as the catalyst. No other additives
      are required for this transformation, thus avoiding the use of toxic transition
      metal catalysts, strong bases, or large amounts of other organic additives. This
      greener protocol provides a new strategy to achieve direct aromatic C-H
      functionalization and offers a new example of cost-effective and environmentally
      benign access to biaryls.

PMID- 24288233
TI  - Effects of nanoporous alumina on inflammatory cell response.
AB  - The present study focuses on the effects of nanoscale porosity on inflammatory
      response in vitro and in vivo. Nanoporous alumina membranes with different pore
      sizes, 20 and 200 nm in diameter, were used. We first evaluated cell/alumina
      interactions in vitro by observing adhesion, proliferation, and activation of a
      murine fibroblast and a macrophage cell line. To investigate the chronic
      inflammatory response, the membranes were implanted subcutaneously in mice for 2
      weeks. Cell recruitment to the site of implantation was determined by histology
      and the production of cytokines was measured by protein array analysis. Both in
      vitro and in vivo studies showed that 200 nm pores induced a stronger
      inflammatory response as compared to the alumina with 20 nm pores. This was
      observed by an increase in macrophage activation in vitro as well as higher cell
      recruitment and generation of proinflammatory cytokines around the alumina with
      200 nm pores, in vivo. Our results suggest that nanofeatures can be modulated in
      order to control the inflammatory response to implants.

PMID- 24288234
TI  - Association of protein expression in isolated milk epithelial cells and cis-9,
      trans-11 conjugated linoleic acid proportions in milk from dairy cows.
AB  - BACKGROUND: The effects of the individual variation among dairy cows on the
      synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) are still not well
      characterised. Therefore, the protein expression profiles of isolated milk
      epithelial cells (MECs) were detected by two-dimensional electrophoresis and
      their correlation with the various proportion of cis-9, trans-11 CLA were
      evaluated. RESULTS: Although animals were offered the same diet, the proportion
      of cis-9, trans-11 CLA in group High (1.02 +/- 0.10%) was twice as high as that
      in group Low (0.59 +/- 0.14%) (P < 0.05). MECs with the characteristics of native
      epithelial cells were successfully isolated from the milk and these cells had no
      obvious RNA degradation or were hardly contaminated with leucocytes or blood red
      cells. Moreover, the protein expression pattern of cathelicidin 5 in isolated
      MECs was positive, whereas annexin I (confirmed by real-time polymerase chain
      reaction), ZW10 interactor and kappa-casein were negatively related to the
      proportion of cis-9, trans-11 CLA in the milk fat. CONCLUSION: The varied
      individual content of cis-9, trans-11 CLA in cows may be associated with annexin
      I. These findings may provide some theoretical basis for studies concerning the
      effects of the individual variation among dairy cows of the synthesis of cis-9,
      trans-11 CLA. (c) 2013 Society of Chemical Industry.

PMID- 24288235
TI  - Rhodium-catalyzed annulative coupling of 3-phenylthiophenes with alkynes
      involving double C-H bond cleavages.
AB  - Double C?H bond activation took place efficiently upon treatment of 3
      phenylthiophenes with alkynes in the presence of a rhodium catalyst and a copper
      salt oxidant to form the corresponding naphthothiophene derivatives.
      Dehydrogenative coupling with alkenes was also found to occur on the phenyl
      moiety rather than the thiophene ring. These reactions provide straightforward
      synthetic methods for pi-conjugated molecules involving a thiophene unit from
      readily available, simple building blocks. 

PMID- 24288236
TI  - Guinness molecules: identifying lowest-energy structures.

PMID- 24288237
TI  - The sleep effects of tiagabine on the first night of treatment predict post
      traumatic stress disorder response at three weeks.
AB  - INTRODUCTION: We sought to test the hypothesis that improvements in sleep might
      mediate treatment-related improvements in daytime symptoms of post-traumatic
      stress disorder (PTSD). We evaluated whether changes in sleep occurring on the
      first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor)
      administration predicted subsequent PTSD response. METHODS: This was an open
      label three-week polysomnographic (PSG) study of nightly treatment with tiagabine
      dosing from 2-12 mg including 20 adults with PTSD with >=30 min of self-reported
      and PSG wake time after sleep onset (WASO). RESULTS: A treatment night 1 decrease
      in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted
      for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the
      primary outcome measure (p<0.001). Increased night 1 SWS also accounted for 91%
      of the variance in Work/School Impairment and 45% of the variance in Social Life
      Impairment as measured with the Sheehan Disability Scale (p<0.001). These
      relationships were much stronger correlates of three-week outcome than three-week
      sleep effects. CONCLUSIONS: The initial sleep response to tiagabine may mediate
      or be an indicator of the subsequent PTSD response. The findings highlight the
      importance of sleep maintenance and SWS in the treatment of PTSD and also suggest
      a potential relationship between SWS and daytime function.

PMID- 24288238
TI  - The impact of comorbid body dysmorphic disorder on the response to sequential
      pharmacological trials for obsessive-compulsive disorder.
AB  - Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD)
      on the response to sequential pharmacological trials in adult obsessive
      compulsive disorder (OCD) patients. The sequential trial initially involved
      fluoxetine monotherapy followed by one of three randomized, add-on strategies:
      placebo, clomipramine or quetiapine. We included 138 patients in the initial
      phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks.
      We invited 70 non-responders to participate in the add-on trial; as 54 accepted,
      we allocated 18 to each treatment group and followed them for an additional 12
      weeks. To evaluate the combined effects of sex, age, age at onset, initial
      severity, type of augmentation and BDD on the response to sequential treatments,
      we constructed a model using generalized estimating equations (GEE). Of the 39
      patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD
      BDD patients were less likely to be classified as responders than the OCD-non-BDD
      patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not
      significantly associated with a worse response to sequential treatments (z-robust
      = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment
      strategies for OCD did not survive when the analyses were controlled for other
      clinical characteristics. 

PMID- 24288239
TI  - Sorption and desorption of alcohol sulfate surfactants in an agricultural soil.
AB  - Alcohol sulfates are one of the most important types of commercial anionic
      surfactants and may pose serious environmental problems. The present study
      examines the sorption behavior of alcohol sulfates in an agricultural soil using
      a batch reactor and column experiments. Kinetics and equilibrium isotherms of the
      sorption and desorption processes of the following alcohol sulfate homologues
      have been determined: AS-C12, AS-C14, AS-C16 , and AS-C18. Sorption and
      desorption occurred rapidly, and equilibrium was achieved in approximately 1 h.
      The sorbed mass percentages were 35.1% AS-C12 , 67.2% AS-C14 , and 100% for both
      AS-C16 and AS-C18. A pseudo-first-order kinetic model provided an adequate fit of
      data. Sorption and desorption equilibrium data were fitted into 1) a linear
      model, with r(2) values in the ranges 0.712 to 0.988 and 0.736 to 0.983,
      respectively, and 2) a Freundlich model, with r(2) values in the ranges 0.956 to
      0.991 and 0.891 to 0.981, respectively. Continuous-flow experiments in soil
      columns were carried out to obtain the breakthrough curves for each compound. The
      present study provides basic theoretical concepts and key parameters for
      developing mathematical models that simulate the migration of alcohol sulfate
      into agricultural soils.

PMID- 24288240
TI  - Graphene-supported ultrafine metal nanoparticles encapsulated by mesoporous
      silica: robust catalysts for oxidation and reduction reactions.
AB  - Graphene nanosheet-supported ultrafine metal nanoparticles encapsulated by thin
      mesoporous SiO2 layers were prepared and used as robust catalysts with high
      catalytic activity and excellent high-temperature stability. The catalysts can be
      recycled and reused in many gas- and solution-phase reactions, and their high
      catalytic activity can be fully recovered by high-temperature regeneration,
      should they be deactivated by feedstock poisoning. In addition to the large
      surface area provided by the graphene support, the enhanced catalytic performance
      is also attributed to the mesoporous SiO2 layers, which not only stabilize the
      ultrafine metal nanoparticles, but also prevent the aggregation of the graphene
      nanosheets. The synthetic strategy can be extended to other metals, such as Pd
      and Ru, for preparing robust catalysts for various reactions. 

PMID- 24288241
TI  - Mortality of non-participants in cervical screening: Register-based cohort study.
AB  - The selective uptake of screening by healthy participants and its impact on the
      evaluation of screening effectiveness in non-randomized studies have been
      discussed, but hardly studied. We quantified excess mortality among cervical
      screening non-participants compared to participants. Based on Danish healthcare
      registers, we determined women's participation in cervical screening in 1990-1993
      (one screening round) and 1990-1997 (two screening rounds). Women were followed
      until end of 2010. We computed hazard ratios (HR) comparing non-participants' and
      participants' risk of death, and analyzed the impact of age, calendar period of
      screening evaluation, screening intensity, length of follow-up and cause of
      death. After one screening round, the 17-year HR of death in non-participants was
      1.61 (95% CI: 1.59-1.63), with an increasing trend over calendar time. After two
      rounds, regular non-participants had a HR of 2.09 (95% CI: 2.05-2.14) compared to
      regular participants. The HR for human papillomavirus (HPV)-related cancers other
      than cervical cancer was 3.80 (95% CI: 2.67-5.41). Younger women, whose coverage
      rates were higher, had higher all-cause mortality HRs. Women screened more
      frequently than recommended had the same mortality as those screened as
      recommended. Acute illness did not seem to be a major reason for non
      participation, as the excess risk of death was not higher in the first years
      following screening evaluation. Non-participants in cervical screening had
      substantially higher all-cause mortality than participants, and a particularly
      increased risk of HPV-related causes of death. These results indicate that
      improper control for the selective uptake of cervical screening may result in
      overestimating its effectiveness.

PMID- 24288242
TI  - [Psychological performance diagnostics].

PMID- 24288243
TI  - Seminal, clinical and colour-Doppler ultrasound correlations of prostatitis-like
      symptoms in males of infertile couples.
AB  - 'Prostatitis-like symptoms' (PLS) are a cluster of bothersome conditions defined
      as 'perineal and/or ejaculatory pain or discomfort and National Institutes of
      Health-Chronic Prostatitis Symptom Index (NIH-CPSI) pain subdomain score >=4'
      (Nickel's criteria). PLS may originate from the prostate or from other portions
      of the male genital tract. Although PLS could be associated with 'prostatitis',
      they should not be confused. The NIH-CPSI is considered the gold-standard for
      assessing PLS severity. Although previous studies investigated the impact of
      prostatitis, vesiculitis or epididymitis on semen parameters, correlations
      between their related symptoms and seminal or scrotal/transrectal colour-Doppler
      ultrasound (CDU) characteristics have not been carefully determined. And no
      previous study evaluated the CDU features of PLS in infertile men. This study was
      aimed at investigating possible associations among NIH-CPSI (total and subdomain)
      scores and PLS, with seminal, clinical and scrotal/transrectal CDU parameters in
      a cohort of males of infertile couples. PLS of 400 men (35.8 +/- 7.2 years) with
      a suspected male factor were assessed by the NIH-CPSI. All patients underwent,
      during the same day, semen analysis, seminal plasma interleukin 8 (sIL-8, a
      marker of male genital tract inflammation), biochemical evaluation, urine/seminal
      cultures, scrotal/transrectal CDU. PLS was detected in 39 (9.8%) subjects. After
      adjusting for age, waist and total testosterone (TT), no association among NIH
      CPSI (total or subdomain) scores or PLS and sperm parameters was observed.
      However, we found a positive association with current positive urine and/or
      seminal cultures, sIL-8 levels and CDU features suggestive of inflammation of the
      epididymis, seminal vesicles, prostate, but not of the testis. The aforementioned
      significant associations of PLS were further confirmed by comparing PLS patients
      with age-, waist- and TT-matched PLS-free patients (1 : 3 ratio). In conclusion,
      NIH-CPSI scores and PLS evaluated in males of infertile couples, are not related
      to sperm parameters, but mainly to clinical and CDU signs of
      infection/inflammation. 

PMID- 24288244
TI  - Purification and characterization of peroxidase from avocado (Persea americana
      Mill, cv. Hass).
AB  - BACKGROUND: Avocado (Persea americana Mill, cv. Hass) fruit ranks tenth in terms
      of the most important products for Mexico. Avocado products are quite unstable
      due to the presence of oxidative enzymes such as polyphenol oxidase and
      peroxidase. The present study is to characterize the activity of purified avocado
      peroxidase from avocado in order to ascertain the biochemical and kinetic
      properties and their inhibition conditions. RESULTS: Purification was performed
      by Sephacryl S 200 HR gel filtration chromatography and its estimated molecular
      weight was 40 kDa. The zymogram showed an isoelectric point of 4.7. Six
      substrates were tested in order to ascertain the affinity of the enzyme for these
      substrates. The purified peroxidase was found to have low Km (0.296 mM) and high
      catalytic efficiency (2688 mM(-1) s(-1)) using 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid), optimum activity being reached at 51
      degrees C, pH 3.8. The addition of dithiothreitol, beta-mercaptoethanol, ascorbic
      acid, sodium azide, L-cysteine and Tween-20 had high inhibitory effects, while
      metals ions such as Cu(+), Fe(2+) and Mn(2+) had weak inhibitory activity on
      purified avocado peroxidase. CONCLUSION: The purified avocado peroxidase exhibits
      high inhibition (Ki = 0.37 uM) with 1.97 uM n-propyl gallate using ABTS as
      substrate at 51 degrees C, pH 3.8 for 10 min.

PMID- 24288245
TI  - Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of
      beta amyloid expression in SHSY5YAPP+ cells through PPARgamma involvement.
AB  - The amyloidogenic cascade is regarded as a key factor at the basis of Alzheimer's
      disease (AD) pathogenesis. The aberrant cleavage of amyloid precursor protein
      (APP) induces an increased production and a subsequent aggregation of beta
      amyloid (Abeta) peptide in limbic and association cortices. As a result, altered
      neuronal homeostasis and oxidative injury provoke tangle formation with
      consequent neuronal loss. Cannabidiol (CBD), a Cannabis derivative devoid of
      psychotropic effects, has attracted much attention because it may beneficially
      interfere with several Abeta-triggered neurodegenerative pathways, even though
      the mechanism responsible for such actions remains unknown. In the present
      research, the role of CBD was investigated as a possible modulating compound of
      APP processing in SHSY5Y(APP+) neurons. In addition, the putative involvement of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) was explored as a
      candidate molecular site responsible for CBD actions. Results indicated the CBD
      capability to induce the ubiquitination of APP protein which led to a substantial
      decrease in APP full length protein levels in SHSY5Y(APP+) with the consequent
      decrease in Abeta production. Moreover, CBD promoted an increased survival of
      SHSY5Y(APP+) neurons, by reducing their long-term apoptotic rate. Obtained
      results also showed that all, here observed, CBD effects were dependent on the
      selective activation of PPARgamma.

PMID- 24288246
TI  - Surface functionalized mesoporous silica nanoparticles with natural proteins for
      reduced immunotoxicity.
AB  - Mesoporous silica nanoparticles (MSNs) present themselves as one of the most
      promising nano-carriers for drug delivery. To reduce their immunotoxicities, in
      this study, natural proteins of gelatin (Gel), bovine serum albumin (BSA), and
      lysozyme (Lys) were employed as end-caps of MSNs by using succinic anhydride as
      an intermediate linker, thus leading to fabrication of MSNs/protein
      nanocomposites, respectively. Furthermore, combined techniques of SEM, TEM, FTIR,
      and zeta potential instruments were utilized to monitor the construction
      processes of MSNs/protein nanocomposites, respectively. Finally, the
      immunotoxicities of those nanocomposites to macrophage cells (RAW264.7 cells)
      were investigated in detail, i.e., cell morphology, cell viability, nitric oxide
      (NO) production, reactive oxygen species (ROS), and acid phosphatase activity
      (ACP) as well as inflammation cytokine expressions (tumor necrosis factor-alpha
      and interleukin-1beta). All results suggest that macrophages were activated after
      uptaking nanoparticles of SiO2 and MSNs, which subsequently induced severe
      inflammation responses in vitro. In contrast, the inflammation responses of MSNs
      nanocomposites were reduced dramatically after end-capping with those natural
      proteins. Overall, this study accumulates knowledge for the development of MSNs
      based drug delivery systems with reduced immunotoxicity.

PMID- 24288247
TI  - Late pregnancy use of selective serotonin reuptake inhibitors and serotonin and
      norepinephrine reuptake inhibitors is associated with increased risk of
      postpartum haemorrhage.

PMID- 24288248
TI  - Pregnancy obesity is associated with increased rates of all-cause mortality and
      cardiovascular hospital admissions in adult offspring.

PMID- 24288249
TI  - Gestational diabetes: higher animal protein intake during pregnancy is associated
      with increased risk, and higher vegetable protein intake with decreased risk.

PMID- 24288250
TI  - Available evidence suggests women with false-positive mammograms less likely to
      return for screening.

PMID- 24288251
TI  - Are acute and chronic saltwater fish studies required for plant protection and
      biocidal product active substance risk assessment?
AB  - The acute and chronic toxicity of chemicals to fish is routinely assessed using
      fish acute and early life stage (ELS) test results, usually with freshwater
      species. Under some regulations with certain substances, however, data on
      saltwater species may also be required. Evidence from earlier studies suggests
      that saltwater fish species are generally no more sensitive than freshwater
      species and that when they are more sensitive to a substance the difference in
      sensitivity is usually less than a factor of 10. However, most of these studies
      concentrated on acute lethal toxicity results for a wide range of substances and
      across a range of taxonomic groups. In the present study, the authors compare
      freshwater and saltwater acute median lethal concentration (LC50) and chronic ELS
      no-observed-effect concentration (NOEC) results from standardized regulatory
      studies specifically for fish species exposed to the same plant protection or
      biocidal product active substances to determine the value of testing in both
      freshwater and saltwater fish. The results suggest that, in most cases, use of a
      freshwater fish 96-h LC50 or longer-term ELS NOEC should be sufficient to protect
      saltwater species. In a small number of cases (12%), saltwater ELS NOECs were
      more sensitive by a factor >10, although differences in sensitivity were not
      consistent for this small number of substances when 96-h LC50 and longer-term ELS
      NOECs were compared. It is debatable whether such a low probability merits the
      additional animal use required to run saltwater fish tests, especially when
      onshore contaminants released to estuaries and coastal environments are likely to
      be diluted many-fold when compared with concentrations found in freshwaters.

PMID- 24288252
TI  - Production of N3 upon photolysis of solid nitrogen at 3 K with synchrotron
      radiation.
AB  - The photodissociation of gaseous molecular nitrogen has been investigated
      intensively, but the corresponding knowledge in a solid phase is lacking.
      Irradiation of pure solid nitrogen at 3 K with vacuum-ultraviolet light from a
      synchrotron produced infrared absorption lines of product l-N3 at 1657.8 and
      1652.6 cm(-1). The threshold wavelength to generate l-N3 was determined to be
      (143.7+/-1.8) nm, corresponding to an energy of (8.63+/-0.11) eV. Quantum
      chemical calculations support the formation of l-N3 from the reaction N2 +N2,
      possibly through an activated complex l-N4 upon photoexcitation with energy above
      8.63 eV. The results provide a possible application to an understanding of the
      nitrogen cycle in astronomical environments.

PMID- 24288253
TI  - Structure of a complex formed by a protein and a helical aromatic oligoamide
      foldamer at 2.1 A resolution.
AB  - In the search of molecules that could recognize sizeable areas of protein
      surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized
      on solid phase. The foldamers comprise three to five monomers carrying various
      proteinogenic side chains, and exist as racemic mixtures of interconverting right
      handed and left-handed helices. Functionalization of the foldamers by a nanomolar
      ligand of human carbonic anhydrase II (HCA) ensured that they would be held in
      close proximity to the protein surface. Foldamer-protein interactions were
      screened by circular dichroism (CD). One foldamer displayed intense CD bands
      indicating that a preferred helix handedness is induced upon interacting with the
      protein surface. The crystal structure of the complex between this foldamer and
      HCA could be resolved at 2.1 A resolution and revealed a number of unanticipated
      protein-foldamer, foldamer-foldamer, and protein-protein interactions.

PMID- 24288254
TI  - Should repeated TESE be performed following a failed TESE in men with Klinefelter
      Syndrome?
AB  - The main goal of this study was to evaluate the success rate of repeated
      Testicular Sperm Extraction (TESE) in Klinefelter Syndrome (KS). Eighteen
      patients with the diagnosis of KS who had undergone micro TESE previously were re
      evaluated between May 2007 and May 2012. Testes were measured and testicular
      volume was calculated by orchidometer and by scrotal ultrasonography in all
      patients All patients underwent repeated micro TESE. Serum follicle stimulating
      hormone (FSH), luteinizing hormone (LH), testosterone levels and testicular
      volume of the patients with and without successful sperm retrieval were compared
      statistically. A p value of less than 0.05 was considered statistically
      significant. The mean age of the patients was 30.3 years. The mean testicular
      volume was 2.08 and 2.1 mL for right and left testes respectively. The
      comparisons of serum FSH, LH, testosterone levels and testicular volume between
      patients with and without successful sperm retrieval did not show any significant
      difference. Three of the 18 patients who underwent repeated micro TESE, had
      successful sperm retrieval and repeated TESE failed in 15 patients. Three
      patients with successful sperm retrieval underwent intracytoplasmic sperm
      injection using retrieved testicular spermatozoa. Two embryos for each patient
      which were determined as healthy were transferred to the wives of the patients.
      Pregnancy occured in one of them and a healthy female infant was born. We
      conclude that consideration and hope must be given for a repeated micro TESE in
      patients with KS, even with a minimal chance of success. 

PMID- 24288255
TI  - Biodegradable mulch performed comparably to polyethylene in high tunnel tomato
      (Solanum lycopersicum L.) production.
AB  - BACKGROUND: High tunnels in the cool climate of north western Washington state
      improve the growing environment for crops otherwise suited to warmer climates.
      Biodegradable mulch may improve the sustainability of high tunnel vegetable
      production if it performs comparably to polyethylene. Four biodegradable mulch
      treatments (BioAgri, BioTelo, WeedGuardPlus and SB-PLA-10/11/12) were compared to
      black polyethylene and bare ground in high tunnels and open field settings to
      assess the impact of production system and mulch treatment on weed control,
      tomato yield, and fruit quality. RESULTS: Fewer weeds grew in high tunnels than
      in the open field. High tunnels increased total and marketable fruit yields and
      increased individual fruit weight. High tunnel production increased juice content
      and pH of tomato fruit, but decreased total soluble solids, titratable acidity,
      and total phenolics compared to the open field. All mulch treatments except SB
      PLA-10 controlled weeds. BioAgri, BioTelo and polyethylene increased total yields
      by 20%, though marketability was reduced 14% compared to bare ground and
      WeedGuardPlus treatments. CONCLUSION: High tunnels can improve tomato yield and
      affect fruit quality in north western Washington. Biodegradable plastic mulches
      performed comparably to polyethylene in weed control, tomato yield, and fruit
      quality and may, therefore, improve the sustainability of high tunnel vegetable
      production.

PMID- 24288257
TI  - [Transfer of Preventive Interventions into Health Care Provision].
AB  - Successful transfer of evidence based prevention programs and interventions in
      health care is a precondition for improvement of public health. The BMBF research
      focus on prevention contained substantial transfer experiences that have been
      analysed. As a result, a set up of a new research focus including specific
      methodology was recommended. The paper summarizes the KNP transfer results. 

PMID- 24288256
TI  - Commonality and differences of methylation signatures in the plasma of patients
      with pancreatic cancer and colorectal cancer.
AB  - Profiling of DNA methylation status of specific genes is a way to screen for
      colorectal cancer (CRC) and pancreatic cancer (PC) in blood. The commonality of
      methylation status of cancer-related tumor suppressor genes between CRC and PC is
      largely unknown. Methylation status of 56 cancer-related genes was compared in
      plasma of patients in the following cohorts: CRC, PC and healthy controls. Cross
      validation determined the best model by area under ROC curve (AUC) to
      differentiate cancer methylation profiles from controls. Optimal preferential
      gene methylation signatures were derived to differentiate either cancer (CRC or
      PC) from controls. For CRC alone, a three gene signature (CYCD2, HIC and VHL) had
      an AUC 0.9310, sensitivity (Sens) = 0.826, specificity (Spec) = 0.9383. For PC
      alone, an optimal signature consisted of five genes (VHL, MYF3, TMS, GPC3 and
      SRBC), AUC 0.848; Sens = 0.807, Spec = 0.666. Combined PC and CRC signature or
      "combined cancer signature" was derived to differentiate either CRC and PC from
      controls (MDR1, SRBC, VHL, MUC2, RB1, SYK and GPC3) AUC = 0.8177, Sens = 0.6316
      Spec = 0.840. In a validation cohort, N = 10 CRC patients, the optimal CRC
      signature (CYCD2, HIC and VHL) had AUC 0.900. In all derived signatures (CRC, PC
      and combined cancer signature) the optimal panel used preferential VHL
      methylation. In conclusion, CRC and PC differ in specific genes methylated in
      plasma other than VHL. Preferential methylation of VHL is shared in the optimal
      signature for CRC alone, PC alone and combined PC and CRC. Future investigations
      may identify additional methylation markers informative for the presence of both
      CRC and PC.

PMID- 24288258
TI  - [Can Peers Achieve Access to Socially Burdened Families? Evaluation Results of
      the Programme 'Community Mothers in Berlin-Kreuzberg'].
AB  - This study evaluated a setting-based programme whose goal was to promote the
      healthy upbringing of children in a disadvantaged district through the
      empowerment of mothers. Women from the neighbourhood were trained as community
      mothers (CM) to impart their knowledge in home visitations to other mothers. 67
      CMs were trained. They gained access to 118 families via home visits and to 191
      families in single contacts. Information and support resulted in positive changes
      in all families available for interviews (n=44). The families also gained access
      to the professional help system. 

PMID- 24288259
TI  - Layer-by-layer assembly of silica nanoparticles on 3D fibrous scaffolds:
      enhancement of osteoblast cell adhesion, proliferation, and differentiation.
AB  - Silica nanoparticles were applied onto the fiber surface of an interbonded three
      dimensional polycaprolactone fibrous tissue scaffold by an electrostatic layer-by
      layer self-assembly technique. The nanoparticle layer was found to improve the
      fiber wettability and surface roughness. Osteoblast cells were cultured on the
      fibrous scaffolds to evaluate the biological compatibility. The silica
      nanoparticle coated scaffold showed enhanced cell attachment, proliferation, and
      alkaline phosphatase activities. The overall results suggested that interbonded
      fibrous scaffold with silica nanoparticulate coating could be a promising
      scaffolding candidate for various applications in bone repair and regeneration.

PMID- 24288260
TI  - Assessment of ischemic penumbra in patients with hyperacute stroke using amide
      proton transfer (APT) chemical exchange saturation transfer (CEST) MRI.
AB  - Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton
      transfer (APT) MRI has shown promise in animal studies for the prediction of
      infarction risk in ischemic tissue. Here, APT MRI was translated to patients with
      acute stroke (1-24 h post-symptom onset), and assessments of APT contrast,
      perfusion, diffusion, disability and final infarct volume (23-92 days post
      stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute
      onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with
      diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery
      (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were
      calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening)
      and final infarct volume. On average (mean +/- standard deviation), control white
      matter APT values (asymmetry, 0.019 +/- 0.005; Lorentzian, 0.045 +/- 0.006) were
      not significantly different (p > 0.05) from APT values in normal-appearing white
      matter (NAWM) of patients (asymmetry, 0.022 +/- 0.003; Lorentzian, 0.048 +/-
      0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT
      effects compared with NAWM. Representative cases are presented, whereby the APT
      contrast is compared quantitatively with contrast from other imaging modalities.
      The findings vary between patients; in some patients, a trend for a reduction in
      the APT signal in the final infarct region compared with at-risk tissue was
      observed, consistent with tissue acidosis. However, in other patients, no
      relationship was observed in the infarct core and final infarct volume. Larger
      clinical studies, in combination with focused efforts on sequence development at
      clinically available field strengths (e.g. 3.0 T), are necessary to fully
      understand the potential of APT imaging for guiding the hyperacute management of
      patients.

PMID- 24288261
TI  - Combination pharmacotherapy to prevent cardiovascular disease: present status and
      challenges.
AB  - Combination pills containing aspirin, multiple blood pressure (BP) lowering
      drugs, and a statin have demonstrated safety, substantial risk factor reductions,
      and improved medication adherence in the prevention of cardiovascular disease
      (CVD). The individual medications in combination pills are already recommended
      for use together in secondary CVD prevention. Therefore, current information on
      their pharmacokinetics, impact on the risk factors, and tolerability should be
      sufficient to persuade regulators and clinicians to use fixed-dose combination
      pills in high-risk individuals, such as in secondary prevention. Long-term use of
      these medicines, in a polypill or otherwise, is expected to reduce CVD risk by at
      least 50-60% in such groups. This risk reduction needs confirmation in
      prospective randomized trials for populations for whom concomitant use of the
      medications is not currently recommended (e.g. primary prevention). Given their
      additive benefits, the combined estimated relative risk reduction (RRR) in CVD
      from both lifestyle modification and a combination pill is expected to be 70-80%.
      The first of several barriers to the widespread use of combination therapy in CVD
      prevention is physician reluctance to use combination pills. This reluctance may
      originate from the belief that lifestyle modification should take precedence, and
      that medications should be introduced one drug at a time, instead of regarding
      combination pills and lifestyle modification as complementary and additive.
      Second, widespread availability of combination pills is also impeded by the
      reluctance of large pharmaceutical companies to invest in development of novel co
      formulations of generic (or 'mature') drugs. A business model based on 'mass
      approaches' to drug production, packaging, marketing, and distribution could make
      the combination pill available at an affordable price, while at the same time
      providing a viable profit for the manufacturers. A third barrier is regulatory
      approval for novel multidrug combination pills, as there are few precedents for
      the approval of combination products with four or more components for CVD.
      Acceptance of combination therapy in other settings suggests that with concerted
      efforts by academics, international health agencies, research funding bodies,
      governments, regulators, and pharmaceutical manufacturers, combination pills for
      prevention of CVD in those with disease or at high risk (e.g. those with multiple
      risk factors) can be made available worldwide at affordable prices. It is
      anticipated that widespread use of combination pills with lifestyle modifications
      can lead to substantial risk reductions (as much as an 80% estimated RRR) in CVD.
      Heath care systems need to deploy these strategies widely, effectively, and
      efficiently. If implemented, these strategies could avoid several millions of
      fatal and non-fatal CVD events every year worldwide. 

PMID- 24288262
TI  - Enzymatic interconversion of isomorphic fluorescent nucleosides: adenosine
      deaminase transforms an adenosine analogue into an inosine analogue.

PMID- 24288263
TI  - Interactive effects of lambda-cyhalothrin, soil moisture, and temperature on
      Folsomia candida and Sinella curviseta (Collembola).
AB  - The authors investigated whether and how 2 environmental factors could influence
      the toxicity of a pyrethroid to 2 representatives of an important group of soil
      organisms. The impacts of different temperatures (20  degrees C and 26  degrees
      C) and soil moisture levels (30%, 50%, and 70% of water holding capacity) were
      investigated in combination with the insecticide lambda-cyhalothrin on the
      reproduction success of Folsomia candida and Sinella curviseta in a full
      factorial design. Testing was based on the standard collembolan reproduction test
      (Organisation for Economic Co-operation and Development, guideline 232) following
      an effect concentration design. The results showed an effect of environmental and
      chemical factors on the number of juveniles of these animals. Particularly in dry
      soil, the reproduction of both species was reduced, while higher soil moisture
      levels influenced the number of juveniles positively compared with the middle
      soil moisture level. In general, however, higher soil moisture led to increased
      sensitivity to lambda-cyhalothrin. In both organisms, temperature affected the
      toxicity of the pesticide but in different directions: high temperature led to
      higher toxicity in F. candida but to lower toxicity in S. curviseta.

PMID- 24288264
TI  - Utility of P16 expression and Ki-67 proliferation index in ASCUS and ASC-H pap
      tests.
AB  - Current cervical screening uses a combination of cytology and high-risk human
      papillomavirus (HR-HPV) analysis in cases of atypical squamous cells of
      undetermined significance (ASCUS) and atypical squamous cells cannot exclude high
      grade intraepithelial lesion (ASC-H). These diagnoses are subject to
      interobserver variability and HR-HPV analysis can be limited by sampling
      inadequacy. This study correlates immunoexpression of P16 and Ki-67 in residual
      cervicovaginal material against cytology category and HR-HPV status. Eighteen pap
      tests were selected: 8 ASCUS, 4 ASC-H, and 6 controls (2 LSIL and 4 HSIL). Digene
      Hybrid Capture II test was used to detect HR-HPV. The cytospins were stained for
      P16/Ki-67. Pap tests, P16, Ki-67, HR-HPV result and available biopsies were
      correlated. P16 expression correlated with HR-HPV status in 15/17 cases.
      Discordant cases (1 ASCUS and 1 ASC-H) were +P16/-HR-HPV. Ki-67 correlated with
      HR-HPV in 8/15 cases. Discordant cases were +HR-HPV/- Ki-67 (HSIL, LSIL, and ASC
      H one each), and -HR-HPV/+Ki-67 (3 ASCUS, 1 LSIL, 1 ASC-H). Two cases were +
      P16/+ Ki-67/- HR-HPV. None were - P16/- Ki-67/+ HR-HPV. Histologic follow-up in
      13 cases varied from benign to CIN III. Two cases of +P16/ - Ki-67/- HR-HPV had
      benign cervical biopcies. Although a small sample size, our findings show a
      utility for adjunct P16/ Ki-67 in addition to HR-HPV testing in cases of squamous
      atypia when HR-HPVs are non-detected due to low DNA copies, or missed lesions in
      cervical biopsies.

PMID- 24288266
TI  - Structure-property relationship of regenerated spider silk protein
      nano/microfibrous scaffold fabricated by electrospinning.
AB  - The regenerated Araneus ventricosus spider dragline silk protein fibrous scaffold
      with moderate strength and flexibility was fabricated by electrospinning and post
      treatment with 90 vol % acetone. The effect of collection method on the
      morphology of regenerated spider silk protein (RSSP) fibrous scaffold, the
      effects of the post treatment solvents and their concentrations on the molecular
      conformation, crystallinity and mechanical properties were studied. The results
      show that the morphology was affected by the solvent used in the coagulation
      bath. The molecular conformation, crystallinity and mechanical property of this
      scaffold were strongly affected by the kind of post treatment solvent and
      slightly influenced by its concentration when it was higher than 50 vol %. The
      degradation rate of this scaffold was very slow and resulting in little pH change
      of the degradation medium within 5 months. PC 12 cells were cultured on the
      electrospun RSSP fibrous scaffold and in its extraction fluid to examine the
      changes of PC 12 cells after different times of culture. The results show that
      the electrospun RSSP fibrous scaffold had good biocompatibility with PC 12 cells.

PMID- 24288267
TI  - Disposition of midazolam in asphyxiated neonates receiving therapeutic
      hypothermia--a pilot study.
AB  - Moderate hypothermia has become an established therapy for asphyxiated neonates.
      Midazolam is a frequently used sedative for this indication, although it has
      never been investigated how therapeutic hypothermia and asphyxia influence
      midazolam metabolism in neonates.9 asphyxiated newborns were treated with whole
      body hypothermia of 32-34 degrees C for 72 h and all of them received continuous
      midazolam infusion for sedation. Serum concentrations of midazolam and its
      metabolites 1-hydroxy-midazolam and 4-hydroxy-midazolam were measured during
      hypothermia and the rewarming period. Renal and hepatic parameters were assessed
      to take into account the influence of asphyxia related renal or hepatic
      impairment.We found a high interindividual variability of serum midazolam
      concentrations in asphyxiated neonates with therapeutic hypothermia; median
      midazolam concentration was 369.3 ng/ml (minimum 36.6; maximum 3 218.6 ng/ml).
      The population pharmacokinetic model revealed a midazolam clearance of 2.57
      ml/kg/min, comparable to midazolam clearances observed in normothermic critically
      ill neonates. However, midazolam clearance was significantly decreased in
      patients with asphyxia related renal and hepatic impairment.It seems that
      isolated hypothermia does not significantly influence midazolam metabolism.
      However, neonates with asphyxia related hepatic and renal impairment are at risk
      of generating unexpectedly high serum midazolam concentrations. In addition
      pronounced interindividual variability of midazolam metabolism may contribute to
      dangerously high midazolam concentrations.

PMID- 24288265
TI  - Design, synthesis, and biological evaluation of (S)-valine thiazole-derived
      cyclic and noncyclic peptidomimetic oligomers as modulators of human P
      glycoprotein (ABCB1).
AB  - Multidrug resistance caused by ATP binding cassette transporter P-glycoprotein (P
      gp) through extrusion of anticancer drugs from the cells is a major cause of
      failure in cancer chemotherapy. Previously, selenazole-containing cyclic peptides
      were reported as P-gp inhibitors and were also used for co-crystallization with
      mouse P-gp, which has 87 % homology to human P-gp. It has been reported that
      human P-gp can simultaneously accommodate two to three moderately sized molecules
      at the drug binding pocket. Our in silico analysis, based on the homology model
      of human P-gp, spurred our efforts to investigate the optimal size of (S)-valine
      derived thiazole units that can be accommodated at the drug binding pocket.
      Towards this goal, we synthesized varying lengths of linear and cyclic
      derivatives of (S)-valine-derived thiazole units to investigate the optimal size,
      lipophilicity, and structural form (linear or cyclic) of valine-derived thiazole
      peptides that can be accommodated in the P-gp binding pocket and affects its
      activity, previously an unexplored concept. Among these oligomers, lipophilic
      linear (13) and cyclic trimer (17) derivatives of QZ59S-SSS were found to be the
      most and equally potent inhibitors of human P-gp (IC50 =1.5 MUM). As the cyclic
      trimer and linear trimer compounds are equipotent, future studies should focus on
      noncyclic counterparts of cyclic peptides maintaining linear trimer length. A
      binding model of the linear trimer 13 within the drug binding site on the
      homology model of human P-gp represents an opportunity for future optimization,
      specifically replacing valine and thiazole groups in the noncyclic form.

PMID- 24288268
TI  - Human alpha1beta3gamma2L gamma-aminobutyric acid type A receptors: High-level
      production and purification in a functional state.
AB  - Gamma-aminobutyric acid type A receptors (GABA(A)Rs) are the most important
      inhibitory chloride ion channels in the central nervous system and are major
      targets for a wide variety of drugs. The subunit compositions of GABA(A)Rs
      determine their function and pharmacological profile. GABAA Rs are
      heteropentamers of subunits, and (alpha1)2 (beta3)2 (gamma2L)1 is a common
      subtype. Biochemical and biophysical studies of GABA(A)Rs require larger
      quantities of receptors of defined subunit composition than are currently
      available. We previously reported high-level production of active human
      alpha1beta3 GABA(A)R using tetracycline-inducible stable HEK293 cells. Here we
      extend the strategy to receptors containing three different subunits. We
      constructed a stable tetracycline-inducible HEK293-TetR cell line expressing
      human (N)-FLAG-alpha1beta3gamma2L-(C)-(GGS)3 GK-1D4 GABA(A)R. These cells
      achieved expression levels of 70-90 pmol [(3)H]muscimol binding sites/15-cm plate
      at a specific activity of 15-30 pmol/mg of membrane protein. Incorporation of the
      gamma2 subunit was confirmed by the ratio of [(3)H]flunitrazepam to
      [(3)H]muscimol binding sites and sensitivity of GABA-induced currents to
      benzodiazepines and zinc. The alpha1beta3gamma2L GABA(A)Rs were solubilized in
      dodecyl-D-maltoside, purified by anti-FLAG affinity chromatography and
      reconstituted in CHAPS/asolectin at an overall yield of ~ 30%. Typical
      purifications yielded 1.0-1.5 nmoles of [(3)H]muscimol binding sites/60 plates.
      Receptors with similar properties could be purified by 1D4 affinity
      chromatography with lower overall yield. The composition of the purified,
      reconstituted receptors was confirmed by ligand binding, Western blot, and
      proteomics. Allosteric interactions between etomidate and [(3)H]muscimol binding
      were maintained in the purified state.

PMID- 24288269
TI  - Effect of split foliar fertilisation on the quality and quantity of active
      constituents in saffron (Crocus sativus L.).
AB  - BACKGROUND: Saffron (Crocus sativus L.) is one of the most expensive medicinal
      and aromatic plants in the world. Due to the excessive application of chemical
      fertilisers in saffron farms and alkalinity of most cultivated soils, split
      foliar fertilisation has been suggested. The primary goal of this study was to
      propose split foliar fertilisation as a technique in increasing the quality and
      quantity of active constituents in saffron. HPLC analysis was used to quantify
      the most important saffron components; crocins (colour), picrocrocin (taste), and
      safranal (odour). This study was carried out in Kashmar, Iran, to determine the
      effect of split foliar fertilisations on quality and quantity of saffron in 2011
      and 2012. A split-plot design experiment based on randomised complete block with
      three replications was conducted to examine three fertiliser types in three
      regimes for split foliar fertilisation. RESULTS: Statistical analysis showed that
      split foliar fertilisation and the fertiliser type significantly increased
      saffron yield, number of flowers and crocin; whereas it decreased the picrocrocin
      and safranal content of the saffron stigmas (P < 0.05). CONCLUSION: Overall,
      split foliar fertilisation increased saffron yield and colour but decreased the
      taste and the odour of saffron.

PMID- 24288270
TI  - The chemistry of cyborgs--interfacing technical devices with organisms.
AB  - The term "cyborg" refers to a cybernetic organism, which characterizes the
      chimera of a living organism and a machine. Owing to the widespread application
      of intracorporeal medical devices, cyborgs are no longer exclusively a subject of
      science fiction novels, but technically they already exist in our society. In
      this review, we briefly summarize the development of modern prosthetics and the
      evolution of brain-machine interfaces, and discuss the latest technical
      developments of implantable devices, in particular, biocompatible integrated
      electronics and microfluidics used for communication and control of living
      organisms. Recent examples of animal cyborgs and their relevance to fundamental
      and applied biomedical research and bioethics in this novel and exciting field at
      the crossroads of chemistry, biomedicine, and the engineering sciences are
      presented. 

PMID- 24288272
TI  - The covalent bioconjugate of multiwalled carbon nanotube and amino-modified
      linearized plasmid DNA for gene delivery.
AB  - Carbon nanotubes (CNTs) are allotropes of carbon, which have unique physical,
      mechanical, and electronic properties. Among various biomedical applications,
      CNTs also attract interest as nonviral gene delivery systems. Functionalization
      of CNTs with cationic groups enables delivery of negatively charged DNA into
      cells. In contrast to this well-known strategy for DNA delivery, our approach
      included the covalent attachment of linearized plasmid DNA to carboxylated
      multiwalled CNTs (MWCNTs). Carboxyl groups were introduced onto MWCNTs by
      oxidative treatment, and then the carboxyl groups were activated by 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC). The whole pQE-70 vector including the
      gene encoding green fluorescent protein (GFP) was subjected to polymerase chain
      reaction (PCR) using the modified nucleotide N6-(6-Amino)hexyl-2'-deoxyadenosine
      5'-triphosphate. Hence, free amino groups were introduced onto the linearized
      plasmid. Covalent bonding between the amino-modified plasmid DNA and the
      carboxylated MWCNTs was achieved via EDC chemistry. The resulting bioconjugate
      was successfully transformed into chemically competent Escherichia coli cells,
      without necessity of a heat-shock step at 42 degrees C. The presence of Ca(2+) in
      transformation medium was required to neutralize the electrostatic repulsion
      between DNA and negatively charged outer layer of E. coli. The transformants,
      which were able to express GFP were inspected manually on ampicillin agar plates.
      Our study represents a novelty with respect to other noncovalent CNT gene
      delivery systems. Considering the interest for delivery of linear DNA fragments,
      our study could give insights into further studies.

PMID- 24288273
TI  - Passive sampling methods for contaminated sediments: practical guidance for
      selection, calibration, and implementation.
AB  - This article provides practical guidance on the use of passive sampling methods
      (PSMs) that target the freely dissolved concentration (Cfree ) for improved
      exposure assessment of hydrophobic organic chemicals in sediments. Primary
      considerations for selecting a PSM for a specific application include clear
      delineation of measurement goals for Cfree , whether laboratory-based "ex situ"
      and/or field-based "in situ" application is desired, and ultimately which PSM is
      best-suited to fulfill the measurement objectives. Guidelines for proper
      calibration and validation of PSMs, including use of provisional values for
      polymer-water partition coefficients, determination of equilibrium status, and
      confirmation of nondepletive measurement conditions are defined. A hypothetical
      example is described to illustrate how the measurement of Cfree afforded by PSMs
      reduces uncertainty in assessing narcotic toxicity for sediments contaminated
      with polycyclic aromatic hydrocarbons. The article concludes with a discussion of
      future research that will improve the quality and robustness of Cfree
      measurements using PSMs, providing a sound scientific basis to support risk
      assessment and contaminated sediment management decisions.

PMID- 24288274
TI  - Systemic administration of Rosmarinus officinalis attenuates the inflammatory
      response induced by carrageenan in the mouse model of pleurisy.
AB  - Rosmarinus officinalis, also named rosemary, is a native plant from the
      Mediterranean region that is useful for the treatment of inflammatory diseases.
      Studies using experimental models and/or in vitro tests have shown the important
      biological effects of rosemary. In this context, the mechanism of the anti
      inflammatory activity of rosemary must be investigated to support the discovery
      of new substances with anti-inflammatory effects. The aim of the present study
      was to investigate the anti-inflammatory effects of crude extract oil free
      obtained from the leaves of rosemary in an animal model of inflammation, thus
      evaluating its medicinal use for the treatment of inflammatory conditions. Also
      its ethanol, hexane, and ethyl acetate fractions, as well as its isolated
      compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for
      the in vivo experiments. The effect of this herb on the inhibition of the
      leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities,
      nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression
      was determined. The crude extract and its derived fractions, in addition to its
      isolated compounds, inhibited leukocytes and decreased exudation and
      myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate
      and interleukin 17A levels and mRNA expression, besides increasing interleukin 10
      levels and mRNA expression. Rosemary showed important anti-inflammatory activity
      by inhibiting leukocytes and decreasing exudation. These effects were associated
      with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine
      deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti
      inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory
      properties of rosemary and validates its use in folk medicine to treat
      inflammatory diseases such as rheumatism and asthma. 

PMID- 24288275
TI  - Antidiarrhoeal evaluation of root extract, its bioactive fraction, and
      lupinifolin isolated from Eriosema chinense.
AB  - The roots of the plant Eriosema chinense are traditionally used by the tribal
      people of North East India for treatment of diarrhoea. Therefore, the present
      investigation was undertaken to scientifically validate the traditional claim
      that these roots have an antidiarrhoeal effect. Ethanol extract along with three
      fractions, ethyl acetate, chloroform, and hexane, as well as isolated lupinifolin
      from the chloroform fraction, were screened for the normal faecal excretion rate
      and castor oil-induced diarrhoea model. The results demonstrated a significant (p
      < 0.05) reduction in normal faecal output at ethanol extract 400, chloroform
      fraction 100, chloroform fraction 200, and lupinifolin 10 mg/kg p. o. after the
      3rd, 5th, and 7th hours of treatment. Also, the same dose level of ethanol
      extract, chloroform fraction, and lupinifolin depicted maximum protection from
      diarrhoea in the castor oil-induced diarrhoea model showing a ceiling effect at
      chloroform fraction 100 mg/kg p. o. Ethanol extract at 400, its bioactive
      fraction chloroform fraction at 100, and lupinifolin at 10 mg/kg p. o.
      significantly inhibited peristaltic index, intestinal fluid volume, and PGE2
      induced enteropooling. They also restored alterations in biochemical parameters
      such as nitric oxide, total carbohydrates, protein, DNA, superoxide dismutase,
      catalase, and lipid peroxidation. The ethanol extract, chloroform fraction, and
      lupinifolin demonstrated a significant recovery from Na+ and K+ loss and a
      pronounced antibacterial activity against bacterial strains mainly implicated in
      diarrhoea. Phytochemical analysis revealed the ethanol extract and chloroform
      fraction to be highly rich in flavonoids, phenols, alkaloids, and tannin
      contents, whereas lupinifolin (a prenylated flavanone), isolated and quantified
      by HPTLC for the first time, was found to comprise 6.480 % and 6.718 % (w/w) of
      the ethanol extract and chloroform fraction, respectively. The antidiarrhoeal
      activity of the chloroform fraction was found to be the highest, followed by
      those of the ethanol extract and lupinifolin, which may be due to the presence of
      lupinifolin along with other phytoconstituents. Thus, the study scientifically
      validated the antidiarrhoeal potential of the roots from E. chinense, which may
      be attributed to antimotility- and antisecretory-type effects with a potential
      antibacterial activity.

PMID- 24288277
TI  - Nanoparticles of well-defined 4-arm stars made using nanoreactors in water.
AB  - In this work, the use of a nanoreactor is demonstrated to rapidly prepare
      monodisperse polymer nanoparticles in water-based dispersion consisting of 4-arm
      star polymer via the R-group RAFT approach. It is shown that by heating a
      nanoparticle assembler above its lower critical solution temperature (LCST),
      stabilized nanoparticles are formed that act as a template for the 4-arm star
      RAFT-mediated polymerization of styrene. Monodisperse nanoparticles of size
      (between 40 and 90 nm) containing monodisperse polymer of desired molecular
      weight (30-95 k) are obtained with little star-star coupling due to
      compartmentalization. The nanoreactor technique allows independent control over
      the size and molecular weight with a 4-arm star topology. 

PMID- 24288276
TI  - In vitro antiparasitic activity and chemical composition of the essential oil
      obtained from the fruits of Piper cubeba.
AB  - Protozoans of the trypanosomatid family cause the neglected tropical diseases
      leishmaniasis and trypanosomiasis, for which few drugs are available. In this
      context our group has recently reported that the essential oil obtained by steam
      distillation of the fruits of Piper cubeba is active against Schistosoma mansoni.
      Therefore, we have investigated the in vitro effects of the essential oil against
      the trypomastigote and amastigote forms of Trypanosoma cruzi isolated from an
      LLCMK2 cell line culture and the promastigote forms of Leishmania amazonensis.
      The in vitro activity of the essential oil against trypomastigotes of T. cruzi
      increased upon rising concentrations, giving IC50 values of 45.5 and 87.9 ug . mL
      1 against trypomastigotes and amastigotes, respectively. The essential oil was
      not active against L. amazonensis, since it displayed lyses of only 24 % at 400
      ug . mL-1, and an IC50 of 326.5 ug . mL-1. Therefore, the essential oil should be
      further investigated to determine the compounds responsible for the observed
      activities, as well as its mechanism of action.

PMID- 24288278
TI  - Proteomic identification of p38 MAP kinase substrates using in vitro
      phosphorylation.
AB  - Protein phosphorylation is a major mechanism that regulates many basic cellular
      processes. Identification and characterization of substrates for a given protein
      kinase can lead to a better understanding of signal transduction pathways.
      However, it is still difficult to efficiently identify substrates for protein
      kinases. Here, we propose an integrated proteomic approach consisting of in vitro
      dephosphorylation and phosphorylation, phosphoprotein enrichment, and 2D-DIGE.
      Phosphatase treatment significantly reduced the complexity of the
      phosphoproteome, which enabled us to efficiently identify the substrates. We
      employed p38 mitogen-activated protein kinase (p38 MAP kinase) as a model kinase
      and identified 23 novel candidate substrates for this kinase. Seven selected
      candidates were phosphorylated by p38 MAP kinase in vitro and in p38 MAP kinase
      activated cells. This proteomic approach can be applied to any protein kinase,
      allowing global identification of novel substrates. 

PMID- 24288283
TI  - Fluorescence color change of aggregation-induced emission of 4-[bis(4
      methylphenyl)amino]benzaldehyde.
AB  - Together we shine: Fluorescence color change of 4-[bis(4
      methylphenyl)amino]benzaldehyde (BMABA) could be induced by vigorous stirring and
      heating of the suspension. This is attributed to a morphological change of the
      particles from an amorphous state to a crystalline state; therefore, BMABA is
      identified as a new aggregation-induced emission material. 

PMID- 24288284
TI  - Excited-state dynamics of the 2-methylallyl radical.
AB  - Radically exciting! The excited-state dynamics of the 2-methylallyl radical are
      studied by time-resolved photoionization. The radical, which is relevant for
      combustion processes, is generated by pyrolysis from the corresponding bromide.
      The lifetime of the electronically excited B state was measured to be 14 ps and
      shorter. 

PMID- 24288285
TI  - Strain-engineered modulation on the electronic properties of phosphorous-doped
      ZnO.
AB  - The modulation of strain on the electronic properties of ZnO:P is investigated by
      density functional theory calculations. The variation of formation energy (E(f))
      and band structure with strains ranging from -0.1 to 0.1 are considered. Although
      both the conduction band minimum (CBM) and the valence band maximum of ZnO are
      antibonding states, the CBM is more sensitive to strain, reducing the band gap
      with an increase in strain. P-substituted O (PO) defects show poor p-type
      conductivity due to a smaller E(f) and lower lying acceptor levels as a
      consequence of lattice expansion. The E(f) of P-substituted Zn (PZn) defects
      decreases under tension, owing to the release of strong repulsive stress induced
      by excess electrons from PZn. The donor energy band of PZn broadens under tensile
      strain, which benefits n-type conductivity. For Zn vacancies (VZn) and PZn-2VZn
      complexes, the distances between the O atoms around VZn are so large that
      repulsive and attractive interactions become weak, which results in an easy
      release of the strain. We herein present for the first time that the E(f) values
      of VZn and PZn-2VZn complexes decrease under both tension and compression, or in
      the high-pressure rock-salt phase. Under a strain of 0.1 the PZn-2VZn complex
      shows the smallest E(f). Under -0.07 strain the wurtzite/rock-salt phase
      transition occurs and the direct band gap becomes an indirect one. The variation
      of band structures in the rock-salt phase is similar to that in the wurtzite
      phase. Consequently, the p-type conductivity of ZnO:P can be improved with an
      increase in solubility of PZn-2VZn or VZn defects.

PMID- 24288286
TI  - The Viedma deracemization of racemic conglomerate mixtures as a paradigm of
      spontaneous mirror symmetry breaking in aggregation and polymerization.
AB  - Simulations of a chemical kinetics model, based on the free-energy relationships
      of classical primary nucleation theory, show that the deracemization phenomenon
      in systems of achiral or fast racemizing compounds yielding enantiopure crystals
      as the more stable solid phase is a true spontaneous mirror symmetry breaking
      process (SMSB). That is, the achievement of a stationary chiral state is more
      stable than the racemic one. The model translates the free-energy relationships
      determined by the existence of a critical size cluster to a chemical kinetics
      model, in which the consideration of forward and backward reaction rate constants
      avoids the misuse of network parameters that violate thermodynamic constraints
      (microreversibility principle), which would lead to apparent in silico SMSB. The
      model provides qualitative agreement for deracemizations by mechanical attrition
      of visible crystals, as well as for those obtained under temperature gradients.
      The analysis of the effect of the system parameters to obtain a SMSB scenario
      shows that the network possesses the principal characteristics of SMSB networks:
      1) an enantioselective autocatalytic stage, corresponding to the non-linear
      kinetics of enantioselective (homochiral) cluster-to-cluster growth, and 2) the
      mutual inhibition step originating in the backward flow of chiral clusters
      towards smaller achiral clusters, or even to a racemizing monomer. The
      application of such a SMSB kinetic model to enantioselective polymerizations and
      to chiral biopolymers is discussed. 

PMID- 24288287
TI  - The two faces of hydrogen-bond strength on triple AAA-DDD arrays.
AB  - Systems that are connected through multiple hydrogen bonds are the cornerstone of
      molecular recognition processes in biology, and they are increasingly being
      employed in supramolecular chemistry, specifically in molecular self-assembly
      processes. For this reason, the effects of different substituents (NO2, CN, F,
      Cl, Br, OCH3 and NH2) on the electronic structure, and consequently on the
      magnitude of hydrogen bonds in triple AAA-DDD arrays (A=acceptor, D=donor) were
      evaluated in the light of topological [electron localization function (ELF) and
      quantum theory of atoms in molecules (QTAIM)], energetic [Su-Li energy
      decomposition analysis (EDA) and natural bond orbital analysis (NBO)], and
      geometrical analysis. The results based on local H-bond descriptors (geometries,
      QTAIM, ELF, and NBO) indicate that substitutions with electron-withdrawing groups
      on the AAA module tend to strengthen, whereas electron-donating substituents tend
      to weaken the covalent character of the AAA-DDD intermolecular H-bonds, and also
      indicate that the magnitude of the effect is dependent on the position of
      substitution. In contrast, Su-Li EDA results show an opposite behavior when
      compared to local H-bond descriptors, indicating that electron-donating
      substituents tend to increase the magnitude of H-bonds in AAA-DDD arrays, and
      thus suggesting that the use of local H-bond descriptors describes the nature of
      H bonds only partially, not providing enough insight about the strength of such H
      bonds.

PMID- 24288288
TI  - Continuous-flow oxidative cyanation of primary and secondary amines using singlet
      oxygen.
AB  - Primary and secondary amines can be rapidly and quantitatively oxidized to the
      corresponding imines by singlet oxygen. This reactive form of oxygen was produced
      using a variable-temperature continuous-flow LED-photoreactor with a catalytic
      amount of tetraphenylporphyrin as the sensitizer. alpha-Aminonitriles were
      obtained in good to excellent yields when trimethylsilyl cyanide served as an in
      situ imine trap. At 25 degrees C, primary amines were found to undergo oxidative
      coupling prior to cyanide addition and yielded secondary alpha-aminonitriles.
      Primary alpha-aminonitriles were synthesized from the corresponding primary
      amines for the first time, by an oxidative Strecker reaction at -50  degrees C.
      This atom-economic and protecting-group-free pathway provides a route to racemic
      amino acids, which was exemplified by the synthesis of tert-leucine hydrochloride
      from neopentylamine. 

PMID- 24288289
TI  - Optically pure, monodisperse cis-oligodiacetylenes: aggregation- induced
      chirality enhancement.
AB  - Conformational changes in the conjugated backbone of poly- and oligodiacetylenes
      (PDAs and ODAs) play an important role in determining the electronic properties
      of these compounds. At the same time, conformational changes can also result in a
      folded structure that shows helical chirality. Using d-camphor as a chiral
      building block, we have designed a high-yielding, iterative synthesis of
      monodisperse, optically pure cis-oligodiacetylenes (ODAs). cis-ODAs up to the
      tridecamer have been formed, which is the longest monodisperse cis-ODA reported
      to date. UV/Vis spectroscopy suggests a large effective conjugation length in
      THF, likely the result of a linear, planar conformation in this solvent. High
      resolution STM/AFM measurements of the nonamer cast from THF onto HOPG show a
      linear structure. In iPrOH, circular dichroism (CD) spectra suggest the formation
      of chiral aggregates for ODAs with at least nine d-camphor units, based on a
      strong CD response.

PMID- 24288290
TI  - Anti HSV-1 flavonoid derivatives tethered with houttuynin from Houttuynia
      cordata.
AB  - This paper reports the phytochemical investigation of the 50% aq. EtOH extract of
      Houttuynia cordata, an effective TCM and functional food in China, which led to
      the isolation of 17 flavonoids including four new ones. The four new compounds
      were flavonoid derivatives tethered with houttuynin (3-oxododecanal). Each of the
      new compounds was obtained as a pair of inseparable diasteriomeric epimers due to
      the chiral carbon of hemiketal at C-3". This phenomenon is rooted in the ring
      chain tautomerism of the hemiketal functional group in solution, which was proved
      by dynamic NMR experiments. The new compounds 1-4 displayed inhibitory activities
      against herpes simplex virus 1, with respective IC50 values of 38.46, 14.10,
      62.00 and 70.76 uM, which was associated with the medicinal functions of H.
      cordata.

PMID- 24288291
TI  - Secondary metabolites from Eupenicillium parvum and their in vitro binding
      affinity for human opioid and cannabinoid receptors.
AB  - Phytochemical investigation of the soil microfungus Eupenicillum parvum led to
      the isolation of two new compounds: a chromone derivative euparvione (1) and a
      new mycophenolic derivative euparvilactone (2), as well as thirteen known
      compounds. The structures of the new compounds were elucidated by means of
      extensive IR, NMR, and MS data and by comparison of data reported in the
      literature. The structure of the known compound 6 was confirmed by X-ray
      crystallography. Several isolated compounds were evaluated for in vitro binding
      assays using opioid receptors (subtypes delta, kappa, and u) and cannabinoid
      receptors (CB1 and CB2). Compound 10 displayed the best selective u-opioid
      receptor and CB1 receptor binding affinities showing values of 47% and 52% at a
      10 uM concentration, respectively. These findings provide insight into the
      potential therapeutic utility of this class of compounds.

PMID- 24288292
TI  - Antiallergic effects of pigments isolated from green sea urchin
      (Strongylocentrotus droebachiensis) shells.
AB  - This study was undertaken to evaluate possible antiallergic effects of an extract
      of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells.
      Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes
      allergic conjunctivitis, and rabbit local skin irritation. The extract
      significantly reduced, in a dose-dependent manner, the histamine-induced
      contractions of the isolated guinea pig ileum with ID50 =1.2 ug/mL (in
      equivalents of spinochrome B), had an inhibitory effect on the model of ocular
      allergic inflammation surpassing the reference drug olopatadine, and did not show
      any irritating effect in rabbits. The extract predominantly contained polyhydroxy
      1,4-naphthoquinone which would be responsible for the pharmacological activity.
      The active compounds of the extract were evaluated in silico with molecular
      docking. Molecular docking into H1R receptor structures obtained from molecular
      dynamic simulations showed that all spinochrome derivatives bind to the receptor
      active site, but spinochrome monomers fit better to it. The results of the
      present study suggest possibilities for the development of new agents for
      treating allergic diseases on the base of pigments from sea urchins shells.

PMID- 24288293
TI  - Caffeoylated phenylpropanoid glycosides from Brandisia hancei inhibit advanced
      glycation end product formation and aldose reductase in vitro and vessel dilation
      in larval zebrafish in vivo.
AB  - In our continuing efforts to identify effective naturally sourced agents for
      diabetic complications, five caffeoylated phenylpropanoid glycosides, acteoside
      (1), isoacteoside (2), poliumoside (3), brandioside (4), and pheliposide (5) were
      isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These
      isolates (1-5) were subjected to an in vitro bioassay evaluating their inhibitory
      activity on advanced glycation end product formation and rat lens aldose
      reductase activity. All tested compounds exhibited significant inhibition of
      advanced glycation end product formation with IC50 values of 4.6-25.7 uM,
      compared with those of aminoguanidine (IC50=1,056 uM) and quercetin (IC50=28.4
      uM) as positive controls. In the rat lens aldose reductase assay, acteoside,
      isoacteoside, and poliumoside exhibited greater inhibitory effects on rat lens
      aldose reductase with IC50 values of 0.83, 0.83, and 0.85 uM, respectively, than
      those of the positive controls, 3,3-tetramethyleneglutaric acid (IC50=4.03 uM)
      and quercetin (IC50=7.2 uM). In addition, the effect of acteoside on the dilation
      of hyaloid-retinal vessels induced by high glucose in larval zebrafish was
      investigated. Acteoside reduced the diameters of high glucose-induced hyaloid
      retinal vessels by 69% at 10 uM and 81% at 20 uM, compared to the high glucose
      treated control group. These results suggest that B. hancei and its active
      components might be beneficial in the treatment and prevention of diabetic
      vascular complications.

PMID- 24288294
TI  - Bioactive benzofuran neolignans from Aristolochia fordiana.
AB  - Six new benzofuran neolignans (1-6) were isolated from the EtOAc-soluble fraction
      of the aerial part of Aristolochia fordiana, together with twelve known analogues
      (7-18). The structures of the isolated compounds were elucidated by spectroscopic
      methods. All isolates were evaluated for their inhibitory effects on nitric oxide
      production in lipopolysaccaride-activated RAW264.7 macrophages and for their
      cytotoxic activities on three human cancer cell lines. Compound 2 showed
      significant nitric oxide production inhibitory activity with an IC50 value of
      10.00 uM, while compound 16 exhibited cytotoxic activity with an IC50 value of
      11.9 uM against MG-63 and compound 18 of 9.15 uM against HepG2 cell lines,
      respectively.

PMID- 24288296
TI  - Phthalocyanine-based organometallic nanocages: properties and gas storage.
AB  - Phthalocyanine (Pc) molecules are well-known flexible structural units for 1D
      nanotubes and 2D nanosheets. First-principles calculations combined with grand
      canonical Monte Carlo simulations are used to obtain the geometries, electronic
      structures, optical properties, and hydrogen-storage capacities of nanocages
      consisting of six Pc molecules with six Mg or Ca atoms. The primitive Pc cage has
      Th symmetry with twofold degeneracy in the highest occupied molecular orbital
      (HOMO), and threefold degeneracy in the lowest unoccupied molecular orbital
      (LUMO); the corresponding HOMO-LUMO gap is found to be 0.97 eV. The MgPc and CaPc
      cages have Oh symmetry with a HOMO-LUMO gap of 1.24 and 1.13 eV, respectively.
      Optical absorption spectra suggest that the Pc-based cages can absorb infrared
      light, which is different from the visible-light absorption in Pc molecules. We
      further show that the excess uptake of hydrogen on MgPc and CaPc cages at 298 K
      and 100 bar (1 bar=0.1 MPa) is about 3.49 and 4.74 wt%, respectively. The present
      study provides new insight into Pc-based nanostructures with potential
      applications.

PMID- 24288295
TI  - Passive sampling methods for contaminated sediments: scientific rationale
      supporting use of freely dissolved concentrations.
AB  - Passive sampling methods (PSMs) allow the quantification of the freely dissolved
      concentration (Cfree ) of an organic contaminant even in complex matrices such as
      sediments. Cfree is directly related to a contaminant's chemical activity, which
      drives spontaneous processes including diffusive uptake into benthic organisms
      and exchange with the overlying water column. Consequently, Cfree provides a more
      relevant dose metric than total sediment concentration. Recent developments in
      PSMs have significantly improved our ability to reliably measure even very low
      levels of Cfree . Application of PSMs in sediments is preferably conducted in the
      equilibrium regime, where freely dissolved concentrations in the sediment are
      well-linked to the measured concentration in the sampler via analyte-specific
      partition ratios. The equilibrium condition can then be assured by measuring a
      time series or a single time point using passive samplers with different surface
      to volume ratios. Sampling in the kinetic regime is also possible and generally
      involves the application of performance reference compounds for the calibration.
      Based on previous research on hydrophobic organic contaminants, it is concluded
      that Cfree allows a direct assessment of 1) contaminant exchange and equilibrium
      status between sediment and overlying water, 2) benthic bioaccumulation, and 3)
      potential toxicity to benthic organisms. Thus, the use of PSMs to measure Cfree
      provides an improved basis for the mechanistic understanding of fate and
      transport processes in sediments and has the potential to significantly improve
      risk assessment and management of contaminated sediments.

PMID- 24288297
TI  - Rhodium-catalyzed ketone methylation using methanol under mild conditions:
      formation of alpha-branched products.
AB  - The rhodium-catalyzed methylation of ketones has been accomplished using methanol
      as the methylating agent and the hydrogen-borrowing method. The sequence is
      notable for the relatively low temperatures that are required and for the ability
      of the reaction system to form alpha-branched products with ease. Doubly
      alkylated ketones can be prepared from methyl ketones and two different alcohols
      by using a sequential one-pot iridium- and rhodium-catalyzed process. 

PMID- 24288298
TI  - A set of genetically diverged Saccharomyces cerevisiae strains with markerless
      deletions of multiple auxotrophic genes.
AB  - Genome analysis of over 70 Saccharomyces strains revealed the existence of five
      groups of genetically diverged S. cerevisiae wild-type isolates, which feature
      distinct genetic backgrounds and reflect the natural diversity existing among the
      species. The strains originated from different geographical and ecological niches
      (Malaysian, West African, North American, Wine/European and Sake) and represent
      clean, non-mosaic lineages of S. cerevisiae, meaning that their genomes differ
      essentially by monomorphic and private SNPs. In this study, one representative
      strain for each of the five S. cerevisiae clean lineages was selected and mutated
      for several auxotroph genes by clean markerless deletions, so that all dominant
      markers remained available for further genetic manipulations. A set of 50 strains
      was assembled, including eight haploid and two diploid strains for each lineage.
      These strains carry different combinations of leu2?0, lys2?0, met15?0, ura3?0
      and/or ura3?::KanMX-barcoded deletions with marker configurations resembling that
      of the BY series, which will allow large-scale crossing with existing deletion
      collections. This new set of genetically tractable strains provides a powerful
      tool kit to explore the impact of natural variation on complex biological
      processes.

PMID- 24288299
TI  - Inbreeding is associated with lower 2D: 4D digit ratio.
AB  - OBJECTIVES: While consanguineous marriage has been shown to result in a small
      increase in risk of recessive Mendelian disorders among offspring, far less
      research has been conducted on the effects of inbreeding on complex traits. These
      effects, thought to result from increased developmental instability due to loss
      of heterozygosity, are expected to be found more pervasively than rare recessive
      Mendelian traits and are expected to result in increased developmental noise.
      Here, we test for a direct effect of inbreeding on 2D : 4D, a putative indicator
      of prenatal hormonal environment. METHODS: We compared the 2D : 4D ratios of 122
      male and 108 female consanguineous (children of first cousin marriages) high
      school and university students to those of 142 male and 122 females controls.
      RESULTS: Across hands and sex, consanguineous parentage was consistently
      associated with lower, more masculine-typical, digit ratios. Digit ratios were
      1.3-1.9 times more variable among the consanguineous group than the control
      group. While socio-economic status cannot explain the effects seen in our data,
      we found that lower, more masculinized, digit ratios were associated with lower
      family income. CONCLUSIONS: Our results suggest that consanguineous marriages are
      associated with a fetal environment that influences morphological development and
      may have associated behavioral sequelae.

PMID- 24288301
TI  - Research integrity in China.

PMID- 24288306
TI  - Space science. Chinese mission ushers in new era of lunar exploration.

PMID- 24288300
TI  - Occupational sun exposure and risk of melanoma according to anatomical site.
AB  - Although sunburn and intermittent sun exposures are associated with increased
      melanoma risk, most studies have found null or inverse associations between
      occupational (more continuous pattern) sun exposure and melanoma risk. The
      association of melanoma with occupational sun exposure may differ according to
      anatomical site, with some studies finding a positive association with melanoma
      on the head and neck. We examined the association between occupational sun
      exposure (self-reported weekday sun exposure) and melanoma risk according to
      anatomical site, using data from two multicentre population-based case-control
      studies: the Australian Melanoma Family Study (588 cases, 472 controls) and the
      Genes, Environment and Melanoma study (GEM; 1079 cases, 2,181 controls).
      Unconditional logistic regression was used to estimate odds ratios (OR) and their
      95% confidence intervals, adjusting for potential confounders. Occupational sun
      exposure was not positively associated with melanoma risk overall or at different
      body sites in both studies. The GEM study found inverse associations between
      occupational sun exposure and melanoma on the head and neck [OR for highest vs.
      lowest quartile: 0.56, 95% confidence intervals (CI) 0.36-0.86, ptrend 0.02], and
      between the proportion of total sun exposure occurring on weekdays and melanoma
      on the upper limbs (OR for highest vs. lowest quartile: 0.66, 95% CI 0.42-1.02,
      ptrend 0.03). Our results suggest that occupational sun exposure does not
      increase risk of melanoma, even of melanomas situated on the head and neck. This
      finding seemed not to be due to negative confounding of occupational sun exposure
      by weekend sun. 

PMID- 24288307
TI  - Climatology. Clues to supertyphoon's ferocity found in the western Pacific.

PMID- 24288308
TI  - Cancer. Cholesterol forges link between obesity and breast cancer.

PMID- 24288309
TI  - Newsmaker interview: Geoffrey Ling. DARPA aims to rebuild brains. Interview by
      Emily Underwood.

PMID- 24288310
TI  - Science education. New head of advocacy group plans to 'fight the good fight'.

PMID- 24288311
TI  - Public health. Tense vigil in China as nasty flu virus stirs back to life.

PMID- 24288312
TI  - The life force.

PMID- 24288313
TI  - China's publication bazaar.

PMID- 24288314
TI  - An aura of legitimacy.

PMID- 24288315
TI  - The more parasites, the better?

PMID- 24288316
TI  - Open data: crediting a culture of cooperation.

PMID- 24288317
TI  - Open data: a sustainable model.

PMID- 24288318
TI  - Ethics tests for trials.

PMID- 24288319
TI  - Space law. International cooperation on human lunar heritage.

PMID- 24288320
TI  - Astronomy. Calibrating asteroid impact.

PMID- 24288321
TI  - Evolution. Protein expression under pressure.

PMID- 24288322
TI  - Chemistry. Abundant metals give precious hydrogenation performance.

PMID- 24288323
TI  - Engineering. Devices for low-resource health care.

PMID- 24288324
TI  - Microbiology. Genomes from metagenomics.

PMID- 24288325
TI  - Retrospective. Fred Sherman (1932-2013).

PMID- 24288326
TI  - IBI series winner. Exploring the evolution of human mate preference.

PMID- 24288327
TI  - Nanoscale Fe2O3-based catalysts for selective hydrogenation of nitroarenes to
      anilines.
AB  - Production of anilines--key intermediates for the fine chemical, agrochemical,
      and pharmaceutical industries--relies on precious metal catalysts that
      selectively hydrogenate aryl nitro groups in the presence of other easily
      reducible functionalities. Herein, we report convenient and stable iron oxide
      (Fe2O3)-based catalysts as a more earth-abundant alternative for this
      transformation. Pyrolysis of iron-phenanthroline complexes on carbon furnishes a
      unique structure in which the active Fe2O3 particles are surrounded by a nitrogen
      doped carbon layer. Highly selective hydrogenation of numerous structurally
      diverse nitroarenes (more than 80 examples) proceeded in good to excellent yield
      under industrially viable conditions.

PMID- 24288328
TI  - Cobalt precursors for high-throughput discovery of base metal asymmetric alkene
      hydrogenation catalysts.
AB  - Asymmetric hydrogenation of alkenes is one of the most widely used methods for
      the preparation of single enantiomer compounds, especially in the pharmaceutical
      and agrochemical industries. For more than four decades, precious metal complexes
      containing rhodium, iridium, and ruthenium have been predominantly used as
      catalysts. Here, we report rapid evaluation of libraries of chiral phosphine
      ligands with a set of simple cobalt precursors. From these studies, base metal
      precatalysts have been discovered for the hydrogenation of functionalized and
      unfunctionalized olefins with high enantiomeric excesses, demonstrating the
      potential utility of more earth-abundant metals in asymmetric hydrogenation. 

PMID- 24288329
TI  - Amine(imine)diphosphine iron catalysts for asymmetric transfer hydrogenation of
      ketones and imines.
AB  - A rational approach is needed to design hydrogenation catalysts that make use of
      Earth-abundant elements to replace the rare elements such as ruthenium, rhodium,
      and palladium that are traditionally used. Here, we validate a prior mechanistic
      hypothesis that partially saturated amine(imine)diphosphine ligands (P-NH-N-P)
      activate iron to catalyze the asymmetric reduction of the polar bonds of ketones
      and imines to valuable enantiopure alcohols and amines, with isopropanol as the
      hydrogen donor, at turnover frequencies as high as 200 per second at 28 degrees
      C. We present a direct synthetic approach to enantiopure ligands of this type
      that takes advantage of the iron(lI) ion as a template. The catalytic mechanism
      is elucidated by the spectroscopic detection of iron hydride and amide
      intermediates. 

PMID- 24288330
TI  - Imaging the absolute configuration of a chiral epoxide in the gas phase.
AB  - In chemistry and biology, chirality, or handedness, refers to molecules that
      exist in two spatial configurations that are incongruent mirror images of one
      another. Almost all biologically active molecules are chiral, and the correct
      determination of their absolute configuration is essential for the understanding
      and the development of processes involving chiral molecules. Anomalous x-ray
      diffraction and vibrational optical activity measurements are broadly used to
      determine absolute configurations of solid or liquid samples. Determining
      absolute configurations of chiral molecules in the gas phase is still a
      formidable challenge. Here we demonstrate the determination of the absolute
      configuration of isotopically labeled (R,R)-2,3-dideuterooxirane by foil-induced
      Coulomb explosion imaging of individual molecules. Our technique provides
      unambiguous and direct access to the absolute configuration of small gas-phase
      species, including ions and molecular fragments. 

PMID- 24288331
TI  - Hepatitis C virus E2 envelope glycoprotein core structure.
AB  - Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis,
      liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and
      E2 mediate fusion and entry into host cells and are the primary targets of the
      humoral immune response. The crystal structure of the E2 core bound to broadly
      neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture
      composed of a central immunoglobulin-fold beta sandwich flanked by two additional
      protein layers. The CD81 receptor binding site was identified by electron
      microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The
      x-ray and electron microscopy E2 structures differ markedly from predictions of
      an extended, three-domain, class II fusion protein fold and therefore provide
      valuable information for HCV drug and vaccine design. 

PMID- 24288332
TI  - 27-Hydroxycholesterol links hypercholesterolemia and breast cancer
      pathophysiology.
AB  - Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast
      cancers and is associated with a decreased response of tumors to endocrine
      therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite
      of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER
      dependent growth and LXR-dependent metastasis in mouse models of breast cancer.
      The effects of cholesterol on tumor pathology required its conversion to 27HC by
      the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1
      inhibitors. In human breast cancer specimens, CYP27A1 expression levels
      correlated with tumor grade. In high-grade tumors, both tumor cells and tumor
      associated macrophages exhibited high expression levels of the enzyme. Thus,
      lowering circulating cholesterol levels or interfering with its conversion to
      27HC may be a useful strategy to prevent and/or treat breast cancer. 

PMID- 24288333
TI  - Nonenzymatic template-directed RNA synthesis inside model protocells.
AB  - Efforts to recreate a prebiotically plausible protocell, in which RNA replication
      occurs within a fatty acid vesicle, have been stalled by the destabilizing effect
      of Mg(2+) on fatty acid membranes. Here we report that the presence of citrate
      protects fatty acid membranes from the disruptive effects of high Mg(2+) ion
      concentrations while allowing RNA copying to proceed, while also protecting
      single-stranded RNA from Mg(2+)-catalyzed degradation. This combination of
      properties has allowed us to demonstrate the chemical copying of RNA templates
      inside fatty acid vesicles, which in turn allows for an increase in copying
      efficiency by bathing the vesicles in a continuously refreshed solution of
      activated nucleotides. 

PMID- 24288334
TI  - Phycobilisomes supply excitations to both photosystems in a megacomplex in
      cyanobacteria.
AB  - In photosynthetic organisms, photons are captured by light-harvesting antenna
      complexes, and energy is transferred to reaction centers where photochemical
      reactions take place. We describe here the isolation and characterization of a
      fully functional megacomplex composed of a phycobilisome antenna complex and
      photosystems I and II from the cyanobacterium Synechocystis PCC 6803. A
      combination of in vivo protein cross-linking, mass spectrometry, and time
      resolved spectroscopy indicates that the megacomplex is organized to facilitate
      energy transfer but not intercomplex electron transfer, which requires diffusible
      intermediates and the cytochrome b6f complex. The organization provides a basis
      for understanding how phycobilisomes transfer excitation energy to reaction
      centers and how the energy balance of two photosystems is achieved, allowing the
      organism to adapt to varying ecophysiological conditions. 

PMID- 24288335
TI  - Long-distance integration of nuclear ERK signaling triggered by activation of a
      few dendritic spines.
AB  - The late phase of long-term potentiation (LTP) at glutamatergic synapses, which
      is thought to underlie long-lasting memory, requires gene transcription in the
      nucleus. However, the mechanism by which signaling initiated at synapses is
      transmitted into the nucleus to induce transcription has remained elusive. Here,
      we found that induction of LTP in only three to seven dendritic spines in rat CA1
      pyramidal neurons was sufficient to activate extracellular signal-regulated
      kinase (ERK) in the nucleus and regulate downstream transcription factors.
      Signaling from individual spines was integrated over a wide range of time (>30
      minutes) and space (>80 micrometers). Spatially dispersed inputs over multiple
      branches activated nuclear ERK much more efficiently than clustered inputs over
      one branch. Thus, biochemical signals from individual dendritic spines exert
      profound effects on nuclear signaling. 

PMID- 24288336
TI  - Neural activity in human hippocampal formation reveals the spatial context of
      retrieved memories.
AB  - In many species, spatial navigation is supported by a network of place cells that
      exhibit increased firing whenever an animal is in a certain region of an
      environment. Does this neural representation of location form part of the
      spatiotemporal context into which episodic memories are encoded? We recorded
      medial temporal lobe neuronal activity as epilepsy patients performed a hybrid
      spatial and episodic memory task. We identified place-responsive cells active
      during virtual navigation and then asked whether the same cells activated during
      the subsequent recall of navigation-related memories without actual navigation.
      Place-responsive cell activity was reinstated during episodic memory retrieval.
      Neuronal firing during the retrieval of each memory was similar to the activity
      that represented the locations in the environment where the memory was initially
      encoded. 

PMID- 24288337
TI  - Though they may be unaware, newlyweds implicitly know whether their marriage will
      be satisfying.
AB  - For decades, social psychological theories have posited that the automatic
      processes captured by implicit measures have implications for social outcomes.
      Yet few studies have demonstrated any long-term implications of automatic
      processes, and some scholars have begun to question the relevance and even the
      validity of these theories. At baseline of our longitudinal study, 135 newlywed
      couples (270 individuals) completed an explicit measure of their conscious
      attitudes toward their relationship and an implicit measure of their automatic
      attitudes toward their partner. They then reported their marital satisfaction
      every 6 months for the next 4 years. We found no correlation between spouses'
      automatic and conscious attitudes, which suggests that spouses were unaware of
      their automatic attitudes. Further, spouses' automatic attitudes, not their
      conscious ones, predicted changes in their marital satisfaction, such that
      spouses with more positive automatic attitudes were less likely to experience
      declines in marital satisfaction over time. 

PMID- 24288339
TI  - Tubulointerstitial nephritis in systemic lupus erythematosus: innocent bystander
      or ominous presage.
AB  - SLE-associated tubulointerstitial injury (SLE TIN) is increasingly recognized in
      two forms, i.e., secondary and primary. The secondary form coexists with lupus
      glomerulonephritis, whereas the primary form develops against the background of
      no or mild glomerular or vascular involvement. Secondary SLE TIN is frequent, but
      its frequency and severity correlate with the class of the associated lupus
      glomerulonephritis (GN), being almost universal in Class IV lupus GN and less
      frequent in GN of other classes. Although the presence of underlying GN may mask
      its clinical manifestation, secondary SLE TIN has a major prognostic implication
      for the renal outcome. Yet, SLE TIN is not factored in the current therapy
      focused International Society of Nephrology/Renal Pathology Society schema of
      renal lupus classification, and its management remains to be elucidated. The
      pathogenesis of secondary SLE TIN is either immunologic, i.e., the
      tubulointerstitial injury being mediated by SLE-related immunologic mechanisms
      akin to those responsible for lupus GN; or non-immunologic, i.e., a nonspecific
      tubulointerstitial injury secondary to any type of advanced glomerular lesion,
      regardless of etiology. Primary SLE TIN is rare with about 15 reported cases. It
      has a rather uniform and distinctive clinical manifestation including acute
      kidney injury with no or mild proteinuria. It responds well to steroid and
      usually carries a good prognosis. Its pathogenesis is almost certain immunologic,
      with immunoglobulin/complement deposits along the tubular basement membrane in
      each reported case. In spite of these profound clinical implications, the current
      review underlies a limited knowledge on the pathobiology of SLE TIN.

PMID- 24288340
TI  - Regional analgesia for video-assisted thoracic surgery: a systematic review.
AB  - Video-assisted thoracic surgery (VATS) is emerging as the standard surgical
      procedure for both minor and major oncological lung surgery. Thoracic epidural
      analgesia (TEA) and paravertebral block (PVB) are established analgesic golden
      standards for open surgery such as thoracotomy; however, there is no gold
      standard for regional analgesia for VATS. This systematic review aimed to assess
      different regional techniques with regard to effect on acute postoperative pain
      following VATS, with emphasis on VATS lobectomy. The systematic review of PubMed,
      The Cochrane Library and Embase databases yielded 1542 unique abstracts; 17
      articles were included for qualitative assessment, of which three were studies on
      VATS lobectomy. The analgesic techniques included TEA, multilevel and single PVB,
      paravertebral catheter, intercostal catheter, interpleural infusion and long
      thoracic nerve block. Overall, the studies were heterogeneous with small numbers
      of participants. In comparative studies, TEA and especially PVB showed some
      effect on pain scores, but were often compared with an inferior analgesic
      treatment. Other techniques showed no unequivocal results. No clear gold standard
      for regional analgesia for VATS could be demonstrated, but a guide of factors to
      include in future studies on regional analgesia for VATS is presented. 

PMID- 24288341
TI  - Ruptured saphenous vein graft aneurysm.
AB  - Ruptured saphenous vein graft (SVG) aneurysm is a rare source of significant
      morbidity and mortality. SVG is a common technique of coronary artery bypass
      grafting (CABG), but vein graft aneurysm and ruptured SVG aneurysm have not
      received the required attention as only few case reports exist. We present the
      case of a 50-year old man with ruptured vein graft aneurysm who had significant
      postoperative complications following surgery, and outline some
      preventive/management strategies. 

PMID- 24288338
TI  - The innate growth bistability and fitness landscapes of antibiotic-resistant
      bacteria.
AB  - To predict the emergence of antibiotic resistance, quantitative relations must be
      established between the fitness of drug-resistant organisms and the molecular
      mechanisms conferring resistance. These relations are often unknown and may
      depend on the state of bacterial growth. To bridge this gap, we have investigated
      Escherichia coli strains expressing resistance to translation-inhibiting
      antibiotics. We show that resistance expression and drug inhibition are linked in
      a positive feedback loop arising from an innate, global effect of drug-inhibited
      growth on gene expression. A quantitative model of bacterial growth based on this
      innate feedback accurately predicts the rich phenomena observed: a plateau-shaped
      fitness landscape, with an abrupt drop in the growth rates of cultures at a
      threshold drug concentration, and the coexistence of growing and nongrowing
      populations, that is, growth bistability, below the threshold. 

PMID- 24288342
TI  - The impact of race and postoperative atrial fibrillation on operative mortality
      after elective coronary artery bypass grafting.
AB  - OBJECTIVE: Black patients are less likely to develop postoperative atrial
      fibrillation (POAF) following coronary artery bypass grafting (CABG) than whites.
      However, the influence of race and POAF on operative mortality has not been
      examined. The objective of this study was to determine the influence of race and
      POAF on operative mortality after CABG. METHODS: Patients undergoing elective
      CABG between 1992 and 2011 were included. Operative mortality was compared
      between patients with and those without new-onset POAF by race. Relative risk
      (RR) and 95% confidence intervals (CI) were computed using Poisson (robust
      variance estimates) and log-binomial regression models. RESULTS: A total of 1215
      (23%) patients developed POAF (white n=1060; black n=155) following CABG
      (N=5387). Operative mortality differed by POAF status within race category (white
      POAF: adjusted RR=1.4, 95% CI=0.86-2.2; black POAF: adjusted RR=5.0, 95% CI=1.9
      13; Pinteraction=0.0016). Black POAF patients had a 2-fold increased risk of
      operative death compared with white POAF patients (Padjusted=0.052). CONCLUSION:
      POAF was observed to be a stronger predictor of operative mortality in black
      compared with white patients undergoing elective CABG.

PMID- 24288343
TI  - Finding the optimal balance between extending limits and achieving outcomes.

PMID- 24288344
TI  - Regional risk assessment of the Puyallup River Watershed and the evaluation of
      low impact development in meeting management goals.
AB  - The Relative Risk Model (RRM) is a tool used to calculate and assess the
      likelihood of effects to endpoints when multiple stressors occur in complex
      ecological systems. In this study, a Bayesian network was used to calculate
      relative risk and estimate uncertainty (BN-RRM) in the Puyallup River Watershed.
      First, we calculated the risk of prespawn mortality of coho salmon. Second, we
      evaluated the effect of low impact development (LID) as a means to reduce risk.
      Prespawner mortality in coho salmon within the Puyallup watershed was the
      endpoint selected for this study. A conceptual model showing causal pathways
      between stressors and endpoints was created to show where linkages exist. A
      relative risk gradient was found throughout the watershed. The lowest risk was
      found in risk regions with the least urban development, and the greatest risk of
      prespawner mortality was found in the highly urbanized risk regions with the
      largest amounts of impervious surface. LID did reduce risk but only when
      implemented at high intensities within the urban watersheds. The structure of the
      BN-RRM also provides a framework for water quality- and quantity-related
      endpoints within this and other watersheds. The framework is also useful for
      evaluating different strategies for remediation or restoration activities. The
      adaptability of using BNs for a relative risk assessment provides opportunities
      for the model to be adapted for other watersheds in the Puget Sound and Salish
      Sea region.

PMID- 24288345
TI  - Transoral robotic surgery vs transoral laser microsurgery for resection of
      supraglottic cancer: a pilot surgery.
AB  - BACKGROUND: Transoral laser microsurgery (TLM) is a mature approach to
      supraglottic cancer, while transoral robotic surgery (TORS) is emerging. The
      present study compared these approaches. METHODS: The first 10 patients (2002
      2005) given TLM were compared with the first 10 (2007-2011) given TORS for cT1-3
      cN0-cN2c supraglottic cancer. RESULTS: A feeding tube was used in four TLM and
      seven TORS patients. Margins were more often positive, but operating times
      shorter, in TORS. All 10 TORS patients are without evidence of disease, but only
      six TLM patients remain disease-free after much longer follow-up. TORS was
      considerably less uncomfortable and fatiguing for the surgeon. CONCLUSIONS: TORS
      seems as safe and effective as TLM. Shorter TORS operating times are probably
      attributable to prior experience with TLM. For laryngeal exposure, length of tube
      placement and margin evaluability, TLM was superior; however, this may change as
      TORS develops and transoral robotic instruments are optimized.

PMID- 24288346
TI  - Oocyte quality in mice is affected by a mycotoxin-contaminated diet.
AB  - Mycotoxins, such as deoxynivalenol (DON), zearalenone (ZEN), and aflatoxin (AF),
      are commonly found in many food commodities and may impair the growth and
      reproductive efficiency of animals and humans. We investigated the effects of a
      mycotoxin-contaminated diet on mouse oocyte quality. Maize contaminated with DON
      (3.875 mg/kg), ZEN (1,897 MUg/kg), and AF (806 MUg/kg) was incorporated into a
      mouse diet at three different levels (0, 15, and 30% w/w). After 4 weeks, ovarian
      and germinal vesicle oocyte indices decreased in mycotoxin-fed mice. Oocytes from
      these mice exhibited low developmental competence with reduced germinal vesicle
      breakdown and polar body extrusion rates. Embryo developmental competence also
      showed a similar pattern, and the majority of embryos could not develop to the
      morula stage. Actin expression was also reduced in both the oocyte cortex and
      cytoplasm, which was accompanied by decreased expression of the actin nucleation
      factors profilin-1 and mDia1. Moreover, a large percentage of oocytes derived
      from mice that were fed a mycotoxin-contaminated diet exhibited aberrant spindle
      morphology, a loss of the cortical granule-free domain, and abnormal
      mitochondrial distributions, which further supported the decreased oocyte
      quality. Thus, our results demonstrate that mycotoxins are toxic to the mouse
      reproductive system by affecting oocyte quality.

PMID- 24288348
TI  - Lineage determination in acute leukemias.

PMID- 24288347
TI  - Bacteria-triggered release of antimicrobial agents.
AB  - Medical devices employed in healthcare practice are often susceptible to
      microbial contamination. Pathogenic bacteria may attach themselves to device
      surfaces of catheters or implants by formation of chemically complex biofilms,
      which may be the direct cause of device failure. Extracellular bacterial lipases
      are particularly abundant at sites of infection. Herein it is shown how active or
      proactive compounds attached to polymeric surfaces using lipase-sensitive
      linkages, such as fatty acid esters or anhydrides, may be released in response to
      infection. Proof-of-concept of the responsive material is demonstrated by the
      bacteria-triggered release of antibiotics to control bacterial populations and
      signaling molecules to modulate quorum sensing. The self-regulating system
      provides the basis for the development of device-relevant polymeric materials,
      which only release antibiotics in dependency of the titer of bacteria surrounding
      the medical device. 

PMID- 24288349
TI  - Immunohistochemical evaluation of EGFR expression in lip squamous cell carcinoma.
      Correlation with clinicopathological characteristics.
AB  - BACKGROUND: The majority of lip cancer is the squamous cell carcinoma (SCC) type
      that exhibits clinical and biological characteristics intermediate between skin
      and oral SCC. The aim of this study was to assess the impact of epidermal growth
      factor receptor (EGFR) expression on prognosis of lip squamous cell carcinoma
      (LSCC) and to relate it with clinicopathological features. The role of EGFR
      expression as a possible therapeutic target was also discussed. METHODS: A series
      of 55 patients with LSCC was analyzed. EGFR expression was determined by
      standardized immunohistochemistry (pharmDx assay) and evaluated by both manual
      and automated image analysis (ACIS III). The Kappa statistic test was used to
      evaluate the concordance of manual and automated scores. EGFR results were
      correlated with clinicopathologic characteristics. Statistical differences
      between proportions were determined by the chi-squared test (with linear-by
      linear correction where appropriate). The Mann-Whitney and the Kruskal-Wallis
      test were employed for comparison of continuous variables. RESULTS: Correlation
      between manual and automated score was obtained in 50/55 cases (90.9%). EGFR
      expression was absent or weak in 14 cases (25.5%); borderline (2+) in 20 cases
      (36.4%) and positive (3+) in 21 cases (38.2%). Significant relationships were
      found between EGFR expression and tumour ulceration (p=0.022) and tumour
      thickness (p=0.002) and width (p=0.021). CONCLUSIONS: Our results revealed EGFR
      high expression in LSCC and its relationship with bad prognosis criteria (tumour
      size and ulceration).

PMID- 24288350
TI  - Selective turn-on fluorescence assay of 6-thioguanine by using harmine-modified
      silver nanoparticles.
AB  - This article reports on a novel fluorescence resonance energy transfer (FRET)
      system between harmine and silver nanoparticles (AgNPs), in which harmine acts as
      the donor and AgNPs act as the acceptor. As a result of FRET, harmine
      fluorescence is quenched efficiently with a corresponding Stern-Volmer constant
      of 3.61 * 10(11)  L/mol. It was found that upon addition of the anticancer drug,
      6-thioguanine (6-TG), the fluorescence was recovered due to the competitive
      adsorption of this compound onto AgNPs. Based on this effect, a selective turn-on
      fluorescence sensor was developed for the determination of 6-TG. Under optimum
      conditions, the enhanced fluorescence intensity displays a linear relationship
      with the concentration of 6-TG in the range 1.5 * 10(-8) -7.5 * 10(-7)  M with a
      detection limit of 9.7 nM. The developed method was applied to the determination
      of this drug in a pharmaceutical preparation and human plasma samples.

PMID- 24288351
TI  - Transoral robotic surgery of the parapharyngeal space: a case series and
      systematic review.
AB  - BACKGROUND: The purpose of this study was to evaluate the current use of
      transoral robotic surgery (TORS) in the treatment of parapharyngeal space (PPS)
      neoplasms through a case series and systematic analysis. METHODS: A case series
      review of 4 patients was combined with a PubMed, Web of Science, and Scopus
      search that identified 82 reports. Fifty-three articles remained after screening
      for duplicates, finally, 8 reports with adequate patient data were included.
      Statistical analyses and graphical representations were performed with Microsoft
      Excel (Redmond, WA) and GraphPad Prism software (La Jolla, CA). RESULTS: Forty
      four patients had TORS resection of PPS neoplasms. Overall, mean length of stay
      was 3.0 days with mean time to oral diet of 1.0 day. There were no recurrences
      but there was a mean follow-up time of only 18.5 months. Twenty-nine of these
      neoplasms (65.9%) were pleomorphic adenomas of which 7 (24%) had unintended
      capsule violation or tumor fragmentation during surgery and 2 patients had
      pharyngeal dehiscence that was managed conservatively. There were no
      neurovascular complications. CONCLUSION: TORS is a viable approach to resection
      of neoplasms of the PPS with minimal surgical morbidity. However, further long
      term evaluation, especially for pleomorphic adenomas, is needed to define patient
      selection and the role of TORS for PPS salivary gland neoplasms.

PMID- 24288352
TI  - Anatomical feasibility of transferring the obturator and genitofemoral nerves to
      repair lumbosacral plexus nerve root avulsion injuries.
AB  - Nerve transfer is a valid surgical procedure for restoring lower-extremity
      function after lumbosacral plexus nerve root avulsion. We determined the
      anatomical feasibility of transferring the obturator and genitofemoral nerves for
      this purpose. The obturator, genitofemoral and femoral nerves, and the S1 and S2
      nerve roots on both sides were exposed in 10 cadaver specimens. We traced all
      nerves to their origins. The lengths of the obturator and genitofemoral nerves
      were measured from their origins to their exits from the abdominal cavity. The
      transverse and longitudinal diameters of all nerves were measured. Specimens were
      obtained to determine the total number of myelinated fibers in each nerve. The
      proximal part of the left obturator nerve was anastomosed with the distal part of
      the right femoral nerve, between the vertebrae and the peritoneum, with an
      overlap of 2-3 cm. Similarly, the proximal parts of the right obturator and
      genitofemoral nerves were anastomosed with the ipsilateral S1 and S2 nerve roots,
      respectively, with an overlap of 2-4 cm. The obturator nerve contained
      approximately one-third of the number of fibers (4,300-7,800) presenting in the
      femoral nerve (13,500-21,000). Similarly, the number of fibers found in the S1
      nerve root was in the range 5,200-8,900. The genitofemoral nerve contained
      approximately half the number of fibers (3,000-4,500) presenting in the S2 nerve
      root (4,600-8,400). The obturator and genitofemoral nerves could be suitable
      donor nerves for repairing lumbosacral plexus nerve root avulsion.

PMID- 24288353
TI  - Asymptomatic deep vein thrombosis in patients undergoing screening duplex
      ultrasonography.
AB  - BACKGROUND: Because of concerns for propagating clots into pulmonary emboli by
      the placement of pneumatic compression boots (PCBs), the standard of care at our
      institution was to perform a duplex Doppler ultrasound with compression (DUSC)
      before applying PCBs. We sought to determine the rate of asymptomatic preexisting
      deep vein thrombosis (DVT) in hospitalized patients who underwent DUSC before
      PCB. METHODS: We evaluated consecutive patients who underwent lower extremity
      DUSC within 48 hours of admission. All patients were assessed for DVT risk
      factors using the American College of Chest Physicians' criteria (American
      College of Chest Physicians Conference on Antithrombotic/Thrombolytic Therapy:
      Evidence-Based Guidelines, 9th Edition). A t test, Wilcoxon rank sum test, and
      chi(2) or Fisher exact test were used to compare patients characteristics
      according to DVT status. Logistic regression was used to determine the importance
      of each risk factor on the risk of DVT. RESULTS: DUSC was performed during 1136
      hospitalizations; 1071 patients were included in the dataset. Of those, 19
      patients (1.8%) had asymptomatic DVT and had at least 1 risk factor; 16 (84.2%)
      had more than 1 risk factor. The only risk factors that were statistically
      significant were ambulatory dysfunction and thromboembolic disease history.
      CONCLUSION: Few patients have asymptomatic DVT upon admission; all of these
      patients have at least 1 predisposing risk factor. There appears to be no need
      for DUSC prior to initiation of PCBs. DUSC evaluation for DVT may be of value if
      there is a history of previous DVT, ambulatory dysfunction, or more than 3 risk
      factors, as the information may change therapeutic approaches.

PMID- 24288354
TI  - Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view.
AB  - OBJECTIVE: To assess the pharmacogenetic potential of FSH for infertility
      treatment. DESIGN: Review of the literature and genomic databases. METHODS:
      Single-nucleotide polymorphism (SNP) assessed: rs6166 (c.2039A>G, p.N680S),
      rs6165 (c.919A>G, p.T307A), rs1394205 (c.-29G>A) in FSHR, and rs10835638 (c.
      211G>T) in FSHB. Literature search via PubMed. Blast analysis of genomic
      information available in the NCBI nucleotide database. Comparison of allele
      frequency and haplotype distribution using the http://spsmart.cesga.estool.
      RESULTS: All these SNPs appear first in Homo, result in reduced FSH action, and
      are present with variable frequencies and combinations worldwide. Stringent
      clinical studies demonstrate that the FSHR genotype influences serum FSH levels
      and gonadal response in both sexes. Serum FSH levels depend on the -211G>T SNP,
      influencing transcriptional activity of the FSHB promoter. Genotypes reducing FSH
      action are overrepresented in infertile subjects. CONCLUSIONS: Although the
      clinical relevance of the FSHR polymorphisms alone is limited, the combination of
      FSHR and FSHB genotypes has a much stronger impact than either one alone in both
      sexes. About 20% of people are carriers of the alleles associated with lower
      serum FSH levels/reduced FSHR expression or activity, possibly less favorable for
      reproduction. Prospective studies need to investigate whether stratification of
      infertile patients according to their FSHR-FSHB genotypes improves clinical
      efficacy of FSH treatment compared with the current, naive approach. A relative
      enrichment of less favorable FSHR-FSHB genotypes may be related to changes in
      human reproductive strategies and be a marker of some health-related advantage at
      the cost of reduced fertility.

PMID- 24288355
TI  - The prevalence and predictors of active brown adipose tissue in Chinese adults.
AB  - OBJECTIVE: Previous studies have shown that active brown adipose tissue (BAT) is
      present in adults and may play important roles in the regulation of energy
      homeostasis. However, nearly every study has been carried out in patients
      undergoing scanning for cancer surveillance (CS), whose metabolism and BAT
      activity may not reflect those of healthy individuals. The objective of this
      study was to investigate the prevalence and predictors of active BAT in Chinese
      adults, particularly in healthy individuals. DESIGN: A total of 31,088
      consecutive subjects aged >=18 years who had undergone positron emission
      tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this
      study. METHODS: We measured BAT activity via (18)F-fluorodeoxyglucose PET/CT in
      subjects who had undergone scanning for either a routine medical checkup (MC) or
      CS in Shanghai. Then, we investigated the predictors of active BAT, particularly
      in healthy individuals. RESULTS: In both groups, the prevalence of BAT was higher
      in women than in men. Using a multivariate logistic analysis, we found age, sex,
      BMI, and high thyroid glucose uptake to be significant predictors of BAT activity
      in the MC group. Similarly, we found age, sex, and BMI to be significant
      predictors of BAT activity, but not thyroid high glucose uptake, in the CS group.
      CONCLUSIONS: In Chinese adults, BAT activity inversely correlates with BMI and
      thyroid high glucose uptake, which reinforces the central role of brown fat in
      adult metabolism and provides clues to a potential means for treating the
      metabolic syndrome.

PMID- 24288356
TI  - Impact of extent of parotid resection on postoperative wound complications: a
      prospective study.
AB  - BACKGROUND: Sialocele and salivary fistula are common complications after
      parotidectomy. The purpose of the present study was to investigate whether extent
      of parotidectomy influences the incidence of these complications. METHODS: We
      conducted a prospective study of 66 consecutive parotidectomies. Cases undergoing
      skin or bone resection or flap reconstruction were excluded. Patients were
      divided into 2 groups based on extent of surgery: group 1 (extracapsular
      dissection or partial superficial parotidectomy); and group 2 (superficial
      parotidectomy or more extensive resection). The incidence of postoperative
      sialocele, salivary fistula, and facial weakness was studied. RESULTS: Eleven
      patients (16.7%) developed a sialocele, and 4 (6.1%) developed a salivary
      fistula. Group 1 had a significantly higher incidence of wound complications (p =
      .008), but a significantly lower incidence of facial weakness (p = .004).
      CONCLUSION: Less extensive parotid resection seems to be associated with a higher
      incidence of postoperative sialocele and salivary fistula, but is also associated
      with less postoperative facial nerve dysfunction.

PMID- 24288357
TI  - Using structural-nested models to estimate the effect of cluster-level adherence
      on individual-level outcomes with a three-armed cluster-randomized trial.
AB  - Much attention has been paid to estimating the causal effect of adherence to a
      randomized protocol using instrumental variables to adjust for unmeasured
      confounding. Researchers tend to use the instrumental variable within one of the
      three main frameworks: regression with an endogenous variable, principal
      stratification, or structural-nested modeling. We found in our literature review
      that even in simple settings, causal interpretations of analyses with endogenous
      regressors can be ambiguous or rely on a strong assumption that can be difficult
      to interpret. Principal stratification and structural-nested modeling are
      alternative frameworks that render unambiguous causal interpretations based on
      assumptions that are, arguably, easier to interpret. Our interest stems from a
      wish to estimate the effect of cluster-level adherence on individual-level binary
      outcomes with a three-armed cluster-randomized trial and polytomous adherence.
      Principal stratification approaches to this problem are quite challenging because
      of the sheer number of principal strata involved. Therefore, we developed a
      structural-nested modeling approach and, in the process, extended the methodology
      to accommodate cluster-randomized trials with unequal probability of selecting
      individuals. Furthermore, we developed a method to implement the approach with
      relatively simple programming. The approach works quite well, but when the
      structural-nested model does not fit the data, there is no solution to the
      estimating equation. We investigate the performance of the approach using
      simulated data, and we also use the approach to estimate the effect on pupil
      absence of school-level adherence to a randomized water, sanitation, and hygiene
      intervention in western Kenya.

PMID- 24288358
TI  - Modeling human epilepsy by TALEN targeting of mouse sodium channel Scn8a.
AB  - To evaluate the efficiency of TALEN technology for introducing mutations into the
      mouse genome we targeted Scn8a, a member of a multigene family with nine closely
      related paralogs. Our goal was to generate a model of early onset epileptic
      encephalopathy by introduction of the Scn8a missense mutation p.Asn1768Asp. We
      used a pair of TALENs that were highly active in transfected cells. The targeting
      template for homologous recombination contained a 4 kb genomic fragment.
      Microinjection of TALENs with the targeting construct into the pronucleus of 350
      fertilized mouse eggs generated 67 live-born potential founders, of which 5 were
      heterozygous for the pathogenic mutation, a yield of 7% correctly targeted mice.
      Twenty-four mice carried one or two Scn8a indels, including 12 frameshift
      mutations and the novel amino acid deletion p.Asn1759del. Nine off-site mutations
      in the paralogs sodium channel genes Scn5a and Scn4a were identified. The data
      demonstrate the feasibility and efficiency of targeting members of multigene
      families using TALENs. The Scn8a(tm) (1768DMm) mouse model will be useful for
      investigation of the pathogenesis and therapy of early onset seizure disorders.

PMID- 24288359
TI  - Vacuum phenomenon: Clinical relevance.
AB  - Vacuum phenomenon (VP) is an anatomical entity of potential confusion in the
      diagnosis and evaluation of joint pathology. Observation of this phenomenon has
      been demonstrated on basic radiographs, computed tomography, and magnetic
      resonance imaging. Although VP is most often associated with degenerative joint
      disease, it is observed with other pathologies. Two problematic scenarios can
      occur: a false-positive diagnosis of serious pathology instead of benign VP and a
      false-negative diagnosis of benign VP with a more serious underlying process
      Despite this potential for confusion, criteria for distinguishing VP from other
      causes of joint pain and for evaluating a suspected case of VP have not been
      fully established. We reviewed the literature to determine underlying mechanism,
      symptomology, associated pathologies, and clinical importance of VP. The
      formation of VP can be explained by gas solubility, pressure-volume
      relationships, and human physiology. CT, GRE-MRI, and multipositional views are
      the best imaging studies to view VP. Although most cases of VP are benign, it can
      be associated with clinical signs and symptoms. VP outside the spine is an
      underreported finding on imaging studies. VP should be on the differential
      diagnosis for joint pain, especially in the elderly. We have proposed criteria
      for diagnosing VP and generated a basic algorithm for its workup. Underreporting
      of this phenomenon shows a lack of awareness of VP on the part of physicians. By
      identifying true anatomic VP, we can prevent harm from suboptimal treatment of
      patients.

PMID- 24288360
TI  - Analysis of an electromagnetic tube placement device versus a self-advancing
      nasal jejunal device for postpyloric feeding tube placement.
AB  - BACKGROUND: Initiation of enteral feeding is an important part of the best
      practice model for critically ill patients. Although nasogastric feeding is
      appropriate for the majority of patients requiring short-term nutrition support,
      certain patients benefit greatly from postpyloric feeding. OBJECTIVE: To
      determine which of 2 specialized enteral tube systems achieved postpyloric
      placement on initial insertion attempt most efficiently. DESIGN: Retrospective
      study comparing the Tiger 2 tube (T2T) and Cortrak Enteral Access System (C-EAS).
      SETTING: Academic medical center, mixed intensive care unit (ICU). PATIENTS: All
      patients admitted to the ICU between 2009 and 2013 who had either a C-EAS or T2T
      placed. MEASUREMENTS: Success rate for postpyloric placement, congruency of real
      time tube placement with x-ray confirmation for C-EAS, and complication rates.
      RESULTS: Seventy-one T2T and 74 C-EAS patients were included. The T2T was
      postpyloric 62% (44/71) of attempted placements. C-EAS was postpyloric 43%
      (32/74) of attempted placements (P = 0.03). C-EAS tracings accurately reflected
      chest x-ray findings 83% and 82% for postpyloric and non-postpyloric insertion,
      respectively. During the entire study period, no adverse events were recorded.
      CONCLUSION: Our institution evaluated 2 different systems designed to ensure
      postpyloric placement of a small bore feeding tube. No literature exists directly
      comparing the 2 systems. Our retrospective review, although limited, showed that
      the T2T was more effective at postpyloric placement on first attempt. Although 1
      benefit of the C-EAS system may be real-time visualization, our practice showed
      this system to be user dependent, which likely led to less success with
      postpyloric placement.

PMID- 24288362
TI  - Proprotein convertase subtilisin/kexin type 9: a plausible link between serum
      resistin levels and cardiovascular events.

PMID- 24288361
TI  - Racial and economic disparities in transplant outcomes: the not-so-hidden
      morbidities.

PMID- 24288363
TI  - Relationship between oxidized LDL, IgM, and IgG autoantibodies to ox-LDL levels
      with recurrent cardiovascular events in Swedish patients with previous myocardial
      infarction.
AB  - We determined whether plasma levels of circulating oxidized low-density
      lipoprotein (LDL; E06), immunoglobulin (Ig) G, and IgM autoantibodies binding to
      malonyldialdehyde-modified LDL (MDA-LDL) may predict cardiovascular events
      (CVEs). Patients (n=123) with a previous myocardial infarction (MI) were
      included. The primary end point was defined as any of the following:
      cardiovascular death from any cause, nonfatal reinfarction or stroke,
      percutaneous coronary intervention, coronary artery bypass grafting, and
      hospitalization due to angina pectoris. There were 43 CVEs during the follow-up
      period of 8.4+/-3.5 years. There was no significant difference in the levels of
      E06 and MDA-LDL IgG between the CVE and the event-free group. However, MDA-LDL
      IgM levels were significantly lower in patients in the CVE group (9524+/-6326
      relative light unit [RLU]) compared with the event-free (10,975+/-5398 RLU) group
      (P=.04). In conclusion, levels of MDA-LDL IgM were associated with an increased
      risk of CVE in patients with a previous MI.

PMID- 24288364
TI  - Combining rosuvastatin with angiotensin-receptor blockers of different PPARgamma
      activating capacity: effects on high-density lipoprotein subfractions and
      associated enzymes.
AB  - The effects of combining angiotensin-receptor blockers of different peroxisome
      proliferator-activated receptor gamma-activating capacity with rosuvastatin on
      high-density lipoprotein (HDL) subfractions and associated enzymes in patients
      with mixed dyslipidemia, hypertension, and prediabetes were assessed. Patients (n
      = 151) were randomly allocated to rosuvastatin (10 mg/d) plus telmisartan 80 mg/d
      (RT group, n = 52) or irbesartan 300 mg/d (RI group, n = 48) or olmesartan 20
      mg/d (RO group, n = 51). Total and intermediate HDL cholesterol (HDL-C) levels
      did not change in any group. Large HDL-C increased, while small HDL-C decreased
      significantly in all the groups (P = not significant between the groups). The
      mass of HDL lipoprotein-associated phospholipase A2 (HDL-Lp-PLA2) and the
      activities of paraoxonase 1 remained unchanged in all the groups. However, HDL-Lp
      PLA2 activity increased only in the RT group (+21.4%; P < .01 vs baseline) and
      did not change in the RI (-4.3%; P = .005 vs RT group) and RO (+3.2%; P = .01 vs
      RT) groups. In conclusion, only the combination of rosuvastatin with telmisartan
      increased the possibly antiatherosclerotic HDL-Lp-PLA2 activity. 

PMID- 24288365
TI  - Is being an elderly woman a risk factor for worse outcomes after percutaneous
      coronary intervention? A large cohort study from one center.
AB  - It has remained undefined whether the combination of being elderly (ie, >75 years
      old) and female is a risk factor for worse outcomes after percutaneous coronary
      intervention (PCI). A total of 29 211 consecutive patients who underwent PCI were
      analyzed. Kaplan-Meier estimated 3-year rate of cardiac death was significantly
      higher in elderly females in comparison with all other groups (P < .05). Using
      Cox proportional hazard models, being an elderly female was a significant risk
      factor for cardiac death and cardiac death/MI in comparison with being a young
      female, OR (95% CI): 2.53 (1.15-5.59), 2.26 (1.27-4.03), or young male, OR (95%
      CI): 2.22 (1.26-3.91), 2.25 (1.44-3.51); however, it was not a significant risk
      factor in comparison with being elderly male, OR (95% CI): 1.30 (0.97-1.71),
      1.21(0.94-1.55). Elderly females had worse outcomes after PCI therapy than other
      gender and age groups, but being an elderly female was not an independent risk
      factor for worse PCI outcomes. 

PMID- 24288366
TI  - Underserved patients' perspectives on patient-centered primary care: does the
      patient-centered medical home model meet their needs?
AB  - The patient-centered medical home (PCMH) has gained significant interest as a
      delivery system model that can improve health care quality while reducing costs.
      This study uses focus groups to investigate underserved, chronically ill
      patients' preferences for care and develops a patient-centered framework of
      priorities. Seven major priorities were identified: (a) communication and
      partnership, (b) affordable care, (c) coordinated care, (d) personal
      responsibility, (e) accessible care, (f) education and support resources, and (g)
      the essential role of nonphysician providers in supporting their care. Using the
      framework, we analyzed the PCMH joint principals as developed by U.S. medical
      societies to identify where the PCMH model could be improved to better meet the
      needs of these patients. Four of the seven patient priorities were identified as
      not present in or supported by current PCMH joint principles. The study discusses
      how the PCMH model can better address the needs of low-income, disadvantaged
      patients. 

PMID- 24288367
TI  - Establishment of active chromatin structure at enhancer elements by mixed-lineage
      leukemia 1 to initiate estrogen-dependent gene expression.
AB  - A number of genome-wide analyses have revealed that estrogen receptor alpha
      binding to and regulation of its target genes correlate with binding of FOXA1, a
      pioneer factor, to nearby DNA sites in MCF-7 breast cancer cells. The enhancer
      element-specific histone H3K4me1/2 mark is enriched at the specific FOXA1/ERalpha
      recruitment sites in chromatin, but the mechanism by which these enhancer marks
      are established in chromatin before hormone treatment is unclear. Here, we show
      that mixed-lineage leukemia 1 (MLL1) protein is a key determinant that maintains
      permissive chromatin structure of the TFF1 enhancer region. MLL1 occupies the
      TFF1 enhancer region and methylates H3K4 before hormone stimulation. In vitro,
      MLL1 binds directly to the CpG-rich region of the TFF1 enhancer, and its binding
      is dependent on hypomethylation of DNA. Furthermore, the depletion of MLL1 in MCF
      7 cells results in a dramatic decrease of chromatin accessibility and recruitment
      of FOXA1 and ERalpha to the enhancer element. Our study defines the mechanism by
      which MLL1 nucleates histone H3K4 methylation marks in CpG-enriched regions to
      maintain permissive chromatin architecture and allow FOXA1 and estrogen receptor
      alpha binding to transcriptional regulatory sites in breast cancer cells. 

PMID- 24288368
TI  - Ribosomal Database Project: data and tools for high throughput rRNA analysis.
AB  - Ribosomal Database Project (RDP; http://rdp.cme.msu.edu/) provides the research
      community with aligned and annotated rRNA gene sequence data, along with tools to
      allow researchers to analyze their own rRNA gene sequences in the RDP framework.
      RDP data and tools are utilized in fields as diverse as human health, microbial
      ecology, environmental microbiology, nucleic acid chemistry, taxonomy and
      phylogenetics. In addition to aligned and annotated collections of bacterial and
      archaeal small subunit rRNA genes, RDP now includes a collection of fungal large
      subunit rRNA genes. RDP tools, including Classifier and Aligner, have been
      updated to work with this new fungal collection. The use of high-throughput
      sequencing to characterize environmental microbial populations has exploded in
      the past several years, and as sequence technologies have improved, the sizes of
      environmental datasets have increased. With release 11, RDP is providing an
      expanded set of tools to facilitate analysis of high-throughput data, including
      both single-stranded and paired-end reads. In addition, most tools are now
      available as open source packages for download and local use by researchers with
      high-volume needs or who would like to develop custom analysis pipelines. 

PMID- 24288369
TI  - Mapping Hfq-RNA interaction surfaces using tryptophan fluorescence quenching.
AB  - Hfq is a posttranscriptional riboregulator and RNA chaperone that binds small
      RNAs and target mRNAs to effect their annealing and message-specific regulation
      in response to environmental stressors. Structures of Hfq-RNA complexes indicate
      that U-rich sequences prefer the proximal face and A-rich sequences the distal
      face; however, the Hfq-binding sites of most RNAs are unknown. Here, we present
      an Hfq-RNA mapping approach that uses single tryptophan-substituted Hfq proteins,
      all of which retain the wild-type Hfq structure, and tryptophan fluorescence
      quenching (TFQ) by proximal RNA binding. TFQ properly identified the respective
      distal and proximal binding of A15 and U6 RNA to Gram-negative Escherichia coli
      (Ec) Hfq and the distal face binding of (AA)3A, (AU)3A and (AC)3A to Gram
      positive Staphylococcus aureus (Sa) Hfq. The inability of (GU)3G to bind the
      distal face of Sa Hfq reveals the (R-L)n binding motif is a more restrictive (A
      L)n binding motif. Remarkably Hfq from Gram-positive Listeria monocytogenes (Lm)
      binds (GU)3G on its proximal face. TFQ experiments also revealed the Ec Hfq (A-R
      N)n distal face-binding motif should be redefined as an (A-A-N)n binding motif.
      TFQ data also demonstrated that the 5'-untranslated region of hfq mRNA binds both
      the proximal and distal faces of Ec Hfq and the unstructured C-terminus. 

PMID- 24288370
TI  - Genetic robustness and functional evolution of gene duplicates.
AB  - Gene duplications are a major source of evolutionary innovations. Understanding
      the functional divergence of duplicates and their role in genetic robustness is
      an important challenge in biology. Previously, analyses of genetic robustness
      were primarily focused on duplicates essentiality and epistasis in several
      laboratory conditions. In this study, we use several quantitative data sets to
      understand compensatory interactions between Saccharomyces cerevisiae duplicates
      that are likely to be relevant in natural biological populations. We find that,
      owing to their high functional load, close duplicates are unlikely to provide
      substantial backup in the context of large natural populations. Interestingly, as
      duplicates diverge from each other, their overall functional load is reduced. At
      intermediate divergence distances the quantitative decrease in fitness due to
      removal of one duplicate becomes smaller. At these distances, yeast duplicates
      display more balanced functional loads and their transcriptional control becomes
      significantly more complex. As yeast duplicates diverge beyond 70% sequence
      identity, their ability to compensate for each other becomes similar to that of
      random pairs of singletons. 

PMID- 24288371
TI  - Pfam: the protein families database.
AB  - Pfam, available via servers in the UK (http://pfam.sanger.ac.uk/) and the USA
      (http://pfam.janelia.org/), is a widely used database of protein families,
      containing 14 831 manually curated entries in the current release, version 27.0.
      Since the last update article 2 years ago, we have generated 1182 new families
      and maintained sequence coverage of the UniProt Knowledgebase (UniProtKB) at
      nearly 80%, despite a 50% increase in the size of the underlying sequence
      database. Since our 2012 article describing Pfam, we have also undertaken a
      comprehensive review of the features that are provided by Pfam over and above the
      basic family data. For each feature, we determined the relevance, computational
      burden, usage statistics and the functionality of the feature in a website
      context. As a consequence of this review, we have removed some features, enhanced
      others and developed new ones to meet the changing demands of computational
      biology. Here, we describe the changes to Pfam content. Notably, we now provide
      family alignments based on four different representative proteome sequence data
      sets and a new interactive DNA search interface. We also discuss the mapping
      between Pfam and known 3D structures. 

PMID- 24288372
TI  - Quantifying the role of steric constraints in nucleosome positioning.
AB  - Statistical positioning, the localization of nucleosomes packed against a fixed
      barrier, is conjectured to explain the array of well-positioned nucleosomes at
      the 5' end of genes, but the extent and precise implications of statistical
      positioning in vivo are unclear. We examine this hypothesis quantitatively and
      generalize the idea to include moving barriers as well as nucleosomes actively
      packed against a barrier. Early experiments noted a similarity between the
      nucleosome profile aligned and averaged across genes and that predicted by
      statistical positioning; however, we demonstrate that aligning random nucleosomes
      also generates the same profile, calling the previous interpretation into
      question. New rigorous results reformulate statistical positioning as predictions
      on the variance structure of nucleosome locations in individual genes. In
      particular, a quantity termed the variance gradient, describing the change in
      variance between adjacent nucleosomes, is tested against recent high-throughput
      nucleosome sequencing data. Constant variance gradients provide support for
      generalized statistical positioning in ~ 50% of long genes. Genes that deviate
      from predictions have high nucleosome turnover and cell-to-cell gene expression
      variability. The observed variance gradient suggests an effective nucleosome size
      of 158 bp, instead of the commonly perceived 147 bp. Our analyses thus clarify
      the role of statistical positioning in vivo.

PMID- 24288373
TI  - Collaboration between CpG sites is needed for stable somatic inheritance of DNA
      methylation states.
AB  - Inheritance of 5-methyl cytosine modification of CpG (CG/CG) DNA sequences is
      needed to maintain early developmental decisions in vertebrates. The standard
      inheritance model treats CpGs as independent, with methylated CpGs maintained by
      efficient methylation of hemimethylated CpGs produced after DNA replication, and
      unmethylated CpGs maintained by an absence of de novo methylation. By stochastic
      simulations of CpG islands over multiple cell cycles and systematic sampling of
      reaction parameters, we show that the standard model is inconsistent with many
      experimental observations. In contrast, dynamic collaboration between CpGs can
      provide strong error-tolerant somatic inheritance of both hypermethylated and
      hypomethylated states of a cluster of CpGs, reproducing observed stable bimodal
      methylation patterns. Known recruitment of methylating enzymes by methylated CpGs
      could provide the necessary collaboration, but we predict that recruitment of
      demethylating enzymes by unmethylated CpGs strengthens inheritance and allows CpG
      islands to remain hypomethylated within a sea of hypermethylation. 

PMID- 24288374
TI  - Discrimination between thermodynamic models of cis-regulation using transcription
      factor occupancy data.
AB  - Many studies have identified binding preferences for transcription factors (TFs),
      but few have yielded predictive models of how combinations of transcription
      factor binding sites generate specific levels of gene expression. Synthetic
      promoters have emerged as powerful tools for generating quantitative data to
      parameterize models of combinatorial cis-regulation. We sought to improve the
      accuracy of such models by quantifying the occupancy of TFs on synthetic
      promoters in vivo and incorporating these data into statistical thermodynamic
      models of cis-regulation. Using chromatin immunoprecipitation-seq, we measured
      the occupancy of Gcn4 and Cbf1 in synthetic promoter libraries composed of
      binding sites for Gcn4, Cbf1, Met31/Met32 and Nrg1. We measured the occupancy of
      these two TFs and the expression levels of all promoters in two growth
      conditions. Models parameterized using only expression data predicted expression
      but failed to identify several interactions between TFs. In contrast, models
      parameterized with occupancy and expression data predicted expression data, and
      also revealed Gcn4 self-cooperativity and a negative interaction between Gcn4 and
      Nrg1. Occupancy data also allowed us to distinguish between competing regulatory
      mechanisms for the factor Gcn4. Our framework for combining occupancy and
      expression data produces predictive models that better reflect the mechanisms
      underlying combinatorial cis-regulation of gene expression. 

PMID- 24288375
TI  - Spatio-temporal requirements for transposable element piRNA-mediated silencing
      during Drosophila oogenesis.
AB  - During Drosophila oogenesis, transposable element (TE) repression involves the
      Piwi-interacting RNA (piRNA) pathway which ensures genome integrity for the next
      generation. We developed a transgenic model to study repression of the Idefix
      retrotransposon in the germline. Using a candidate gene KD-approach, we
      identified differences in the spatio-temporal requirements of the piRNA pathway
      components for piRNA-mediated silencing. Some of them (Aub, Vasa, Spn-E) are
      necessary in very early stages of oogenesis within the germarium and appear to be
      less important for efficient TE silencing thereafter. Others (Piwi, Ago3, Mael)
      are required at all stages of oogenesis. Moreover, during early oogenesis, in the
      dividing cysts within the germarium, Idefix anti-sense transgenes escape host
      control, and this is associated with very low piwi expression. Silencing of P
      element-based transgenes is also strongly weakened in these cysts. This region,
      termed the 'Piwiless pocket' or Pilp, may ensure that new TE insertions occur and
      are transmitted to the next generation, thereby contributing to genome dynamics.
      In contrast, piRNA-mediated silencing is strong in germline stem cells in which
      TE mobilization is tightly repressed ensuring the continued production of viable
      germline cysts. 

PMID- 24288376
TI  - PDBe: Protein Data Bank in Europe.
AB  - The Protein Data Bank in Europe (pdbe.org) is a founding member of the Worldwide
      PDB consortium (wwPDB; wwpdb.org) and as such is actively engaged in the
      deposition, annotation, remediation and dissemination of macromolecular structure
      data through the single global archive for such data, the PDB. Similarly, PDBe is
      a member of the EMDataBank organisation (emdatabank.org), which manages the EMDB
      archive for electron microscopy data. PDBe also develops tools that help the
      biomedical science community to make effective use of the data in the PDB and
      EMDB for their research. Here we describe new or improved services, including
      updated SIFTS mappings to other bioinformatics resources, a new browser for the
      PDB archive based on Gene Ontology (GO) annotation, updates to the analysis of
      Nuclear Magnetic Resonance-derived structures, redesigned search and browse
      interfaces, and new or updated visualisation and validation tools for EMDB
      entries. 

PMID- 24288377
TI  - Recent updates and developments to plant genome size databases.
AB  - Two plant genome size databases have been recently updated and/or extended: the
      Plant DNA C-values database (http://data.kew.org/cvalues), and GSAD, the Genome
      Size in Asteraceae database (http://www.asteraceaegenomesize.com). While the
      first provides information on nuclear DNA contents across land plants and some
      algal groups, the second is focused on one of the largest and most economically
      important angiosperm families, Asteraceae. Genome size data have numerous
      applications: they can be used in comparative studies on genome evolution, or as
      a tool to appraise the cost of whole-genome sequencing programs. The growing
      interest in genome size and increasing rate of data accumulation has necessitated
      the continued update of these databases. Currently, the Plant DNA C-values
      database (Release 6.0, Dec. 2012) contains data for 8510 species, while GSAD has
      1219 species (Release 2.0, June 2013), representing increases of 17 and 51%,
      respectively, in the number of species with genome size data, compared with
      previous releases. Here we provide overviews of the most recent releases of each
      database, and outline new features of GSAD. The latter include (i) a tool to
      visually compare genome size data between species, (ii) the option to export data
      and (iii) a webpage containing information about flow cytometry protocols. 

PMID- 24288379
TI  - Mechanical work performed by individual limbs of transfemoral amputees during
      step-to-step transitions: Effect of walking velocity.
AB  - The greater metabolic demand during the gait of people with a transfemoral
      amputation limits their autonomy and walking velocity. Major modifications of the
      kinematic and kinetic patterns of transfemoral amputee gait quantified using gait
      analysis may explain their greater energy cost. Donelan et al. proposed a method
      called the individual limb method to explore the relationships between the gait
      biomechanics and metabolic cost. In the present study, we applied this method to
      quantify mechanical work performed by the affected and intact limbs of
      transfemoral amputees. We compared a cohort of six active unilateral transfemoral
      amputees to a control group of six asymptomatic subjects. Compared to the control
      group, we found that there was significantly less mechanical work produced by the
      affected leg and significantly more work performed by the unaffected leg during
      the step-to-step transition. We also found that this mechanical work increased
      with walking velocity; the increase was less pronounced for the affected leg and
      substantial for the unaffected leg. Finally, we observed that the lesser work
      produced by the affected leg was linked to the increase in the hip flexion moment
      during the late stance phase, which is necessary for initiating knee flexion in
      the affected leg. It is possible to quantify the mechanical work performed during
      gait by people with a transfemoral amputation, using the individual limb method
      and conventional gait laboratory equipment. The method provides information that
      is useful for prosthetic fitting and rehabilitation. 

PMID- 24288378
TI  - Intramolecular binding mode of the C-terminus of Escherichia coli single-stranded
      DNA binding protein determined by nuclear magnetic resonance spectroscopy.
AB  - Single-stranded DNA (ssDNA) binding protein (SSB) is an essential protein to
      protect ssDNA and recruit specific ssDNA-processing proteins. Escherichia coli
      SSB forms a tetramer at neutral pH, comprising a structurally well-defined ssDNA
      binding domain (OB-domain) and a disordered C-terminal domain (C-domain) of ~ 64
      amino acid residues. The C-terminal eight-residue segment of SSB (C-peptide) has
      been shown to interact with the OB-domain, but crystal structures failed to
      reveal any electron density of the C-peptide. Here we show that SSB forms a
      monomer at pH 3.4, which is suitable for studies by high-resolution nuclear
      magnetic resonance (NMR) spectroscopy. The OB-domain retains its 3D structure in
      the monomer, and the C-peptide is shown by nuclear Overhauser effects and
      lanthanide-induced pseudocontact shifts to bind to the OB-domain at a site that
      harbors ssDNA in the crystal structure of the SSB-ssDNA complex. (15)N relaxation
      data demonstrate high flexibility of the polypeptide segment linking the C
      peptide to the OB-domain and somewhat increased flexibility of the C-peptide
      compared with the OB-domain, suggesting that the C-peptide either retains high
      mobility in the bound state or is in a fast equilibrium with an unbound state.

PMID- 24288380
TI  - Case formulation and management using pattern-based formulation (PBF)
      methodology: clinical case 1.
AB  - OBJECTIVE: A tool for psychiatric case formulation known as pattern-based
      formulation (PBF) has been recently introduced. This paper presents an
      application of this methodology in formulating and managing complex clinical
      cases. METHOD: The symptomatology of the clinical presentation has been parsed
      into individual clinical phenomena and interpreted by selecting explanatory
      models. RESULTS: The clinical presentation demonstrates how PBF has been used as
      a clinical tool to guide clinicians' thinking, that takes a structured approach
      to manage multiple issues using a broad range of management strategies. In doing
      so, the paper also introduces a number of patterns related to the observed
      clinical phenomena that can be re-used as explanatory models when formulating
      other clinical cases. CONCLUSION: It is expected that this paper will assist
      clinicians, and particularly trainees, to better understand PBF methodology and
      apply it to improve their formulation skills.

PMID- 24288381
TI  - Nosocomial suicide.
AB  - OBJECTIVE AND METHOD: To consider the possibility that adverse aspects of
      psychiatric hospitalisation may precipitate suicide contributing significantly to
      the increased rate of suicide among inpatients, given little has been published
      about this. RESULTS AND CONCLUSIONS: It is likely that psychiatric
      hospitalisation itself contributes to some inpatient suicides. This has
      significant implications for the delivery of inpatient psychiatric care.

PMID- 24288382
TI  - Somatoform disorders in patients with chronic pain.
AB  - OBJECTIVE: To assess the frequency and characteristics of somatoform disorders in
      patients with chronic pain. METHOD: The study took place in the psychiatric
      outpatient clinic of a rehabilitation hospital. Participants were interviewed
      using the World Health Organization Somatoform Disorders Schedule (WHO-SDS)
      version 2.0. Thirty new and 30 current attendees to the clinic were interviewed
      following referral by pain medicine specialists. RESULTS: Somatoform disorders
      were commonly co-morbid with chronic pain in the study population. Persistent
      somatoform pain disorder (PSPD) was the commonest somatoform disorder. There was
      a significant difference between women and men suffering from somatic autonomic
      dysfunction (SAD). CONCLUSIONS: The findings of this study confirm that
      somatoform disorders are common co-morbid diagnoses in patients with chronic
      pain. Combining psychological treatments with medication, appropriate physical
      treatments and attending to social issues, may indeed improve the well-being of
      such patients.

PMID- 24288383
TI  - Baptism by conference: an effective Royal Australian and New Zealand College of
      Psychiatrists recruitment tool?
AB  - OBJECTIVE: To explore common barriers medical students perceive to choosing
      psychiatry as a medical specialty as reflected in existing literature and the
      authors' own experiences and whether funding student attendance of a Royal
      Australian and New Zealand College of Psychiatrists Congress serves to overcome
      some of these perceptions. CONCLUSIONS: Common barriers to selecting psychiatry
      as a career include stigma due primarily to lack of information about this
      specialty; concerns about personal safety; concerns about losing clinical skills
      and fear of burn-out. Bursaries funding student attendance to the Royal
      Australian and New Zealand College of Psychiatrists 2013 Congress were an
      excellent initiative that gave students a panoramic view of the variety of fields
      within the specialty and exposure to current debates and research, as well as the
      chance to discuss various subspecialties with keynote speakers and other
      professionals working in these areas. Undertaking more outreach activities and on
      campus information sessions targeting final year students may help to further
      combat misperceptions and improve recruitment.

PMID- 24288384
TI  - The art and science of using routine outcome measurement in mental health
      benchmarking.
AB  - OBJECTIVE: To report and critique the application of routine outcome measurement
      data when benchmarking Australian mental health services. METHOD: The experience
      of the authors as participants and facilitators of benchmarking activities is
      augmented by a review of the literature regarding mental health benchmarking in
      Australia. RESULTS: Although the published literature is limited, in practice,
      routine outcome measures, in particular the Health of the National Outcomes
      Scales (HoNOS) family of measures, are used in a variety of benchmarking
      activities. Use in exploring similarities and differences in consumers between
      services and the outcomes of care are illustrated. This requires the rigour of
      science in data management and interpretation, supplemented by the art that comes
      from clinical experience, a desire to reflect on clinical practice and the
      flexibility to use incomplete data to explore clinical practice. CONCLUSIONS:
      Routine outcome measurement data can be used in a variety of ways to support
      mental health benchmarking. With the increasing sophistication of information
      development in mental health, the opportunity to become involved in benchmarking
      will continue to increase. The techniques used during benchmarking and the
      insights gathered may prove useful to support reflection on practice by
      psychiatrists and other senior mental health clinicians.

PMID- 24288385
TI  - Correlation of ELISA optical density with clinical diagnosis of heparin-induced
      thrombocytopenia: a retrospective study of 104 patients with positive anti
      PF4/heparin ELISA.
AB  - BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) for antiplatelet factor 4
      (anti-PF4)/heparin antibodies is expressed in terms of optical density (OD).
      Previous studies have shown correlation between OD and heparin-induced
      thrombocytopenia (HIT) diagnosis. However, these were mainly laboratory based.
      OBJECTIVE: Retrospective correlation of clinical HIT to ELISA OD.
      PATIENTS/METHODS: We conducted a retrospective study involving 104 patients with
      a positive ELISA for anti-PF4/heparin antibodies between 2008 and May 2012. For
      each patient, a clinical diagnosis was adjudicated based on different features
      including "4T scores," laboratory results, and a 3-month clinical follow-up.
      RESULTS: In this study, 28.8% of the patients were HIT positive, and 71.2% HIT
      negative. Patients with positive diagnosis had significantly higher mean OD (2.15
      +/- 0.76 vs 0.83 +/- 0.62). Patients with OD <1.0 only had 3.4% positive
      diagnosis versus 45.5% for OD 1.0 to 2.0 and 78% for >2.0 units. CONCLUSION: This
      study is a clinical confirmation that ELISA OD results are correlated with the
      probability of a clinical diagnosis of HIT.

PMID- 24288386
TI  - Compositional differences in commercially available prothrombin complex
      concentrates.
AB  - Prothrombin complex concentrates (PCCs) are used in the management of bleeding
      complications with conventional oral anticoagulant drugs. Since the activation of
      these complexes results in the generation of factor Xa and IIa, these agents may
      potentially neutralize the newly developed Xa and thrombin inhibitors. Although
      the potency of these agents is defined in units that represent the level of
      factor IX (FIX), other factors including factor II, VII, and X are also present.
      Protein C, protein S, and protein Z are also present. The purpose of this study
      is to compare the compositional differences in the currently available PCCs along
      with the older agents. Measurement of compositional parameters including protein
      and FIX, mass spectrometric analysis of the native and activated PCCs, Western
      blotting studies on the native and activated PCCs for the activation products
      including thrombin, and their effect on blood and plasma coagulation parameters
      were carried out. 

PMID- 24288387
TI  - Treatment of skin and soft tissue infections in a pediatric observation unit.
AB  - OBJECTIVES: To report the success rate of observation unit (OU) treatment of
      pediatric skin and soft tissue infections (SSTIs) and to see if we could identify
      variables at the time of initial evaluation that predicted successful OU
      treatment. METHODS: A retrospective review of children less than 18 years of age
      admitted for SSTI treatment to our OU from the emergency department between
      January 2003 and June 2009. RESULTS: On records review, 853 patients matched
      eligibility criteria; median age was 5.2 years (interquartile range = 2.5-9
      years). Of the 853 patients, 597 (70.0%) met the primary outcome criteria of
      successful OU discharge within 26 hours. Secondary analysis revealed that 82% of
      the patients achieved successful discharge from the OU within 48 hours. Although
      some laboratory variables demonstrated statistical association with success, none
      achieved a combination of high sensitivity and specificity to predict OU failure.
      OU success rates varied by location. Dental and face infections and those of the
      extremities or multiple sites demonstrated OU success rates higher than 65%,
      while infection of the groin, buttocks, trunk, or neck had success rates between
      24% (neck) and 60% (groin). In multivariate analysis, only 3 variables remained
      significant. Unfavorable location was most strongly associated with OU failure,
      followed by C-reactive protein > 4 and then by erythrocyte sedimentation rate >
      20. CONCLUSIONS: Our findings suggest that successful OU treatment is possible in
      a large group of patients needing hospitalization for SSTIs. Consideration of
      infection location may assist the emergency department clinician in determining
      the most appropriate unit for admission.

PMID- 24288388
TI  - Timing of head circumference measurement in newborns.
AB  - AIM: The objective of this study is to compare head circumferences (HCs) measured
      on the day of delivery and on the third day after delivery. METHOD: A total of
      499 children born in the maternity department were recruited for the study. HC
      was measured in centimeters immediately after birth and on the third day after
      delivery. RESULTS: There are statistically significant differences between HC at
      the time of birth and on the third day. Presentation and method of delivery were
      significantly associated with differences in HC. For presentation, we found that
      breech newborns more commonly have smaller HC on day 3 measurements (P = .001).
      For method of delivery, we found that cesarean sections also were more commonly
      associated with having smaller HC on day 3 measurement (P = .02). CONCLUSION:
      Measuring HC on the third day is more clinically valuable because much of the
      effects of molding and birth injuries will have subsided in most newborns.

PMID- 24288389
TI  - Topographic variation of choroidal and retinal thicknesses at the macula in
      healthy adults.
AB  - BACKGROUND/AIMS: To determine the topographic variation of macular choroidal and
      retinal thicknesses (RTs) in normal eyes and their relationship with refractive
      error. METHODS: Spectral domain optical coherence tomography with enhanced depth
      imaging was performed on 124 healthy participants using a standardised imaging
      protocol. Manual segmentation of choroidal boundaries was performed by trained
      graders, and mean choroidal thickness (CT) was compared with mean RT in
      corresponding sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS)
      grid. RESULTS: Mean central subfield CT was 322.2 um. The choroid was thickest at
      the temporal and superior sectors (323.1-338.1 um), followed by inferior sectors
      (314.0-321.8 um), and thinnest at the nasal sectors (232.8-287.8 um). In
      contrast, the retina was thicker nasally (343.4 um) and thinner temporally (287.1
      um). CT was thickest among emmetropes in all ETDRS subfields and became thinner
      progressively among low, moderate and high myopes (p<0.001). The variation of
      both choroidal and RTs among refractive error groups resulted in different
      topographic patterns at the macula. CONCLUSION: There is significant topographic
      variation of choroidal and RTs at different regions of the macula, with
      progressive change of choroidal thickness in all sectors based on the refractive
      status of the eye.

PMID- 24288390
TI  - Conjunctival keratoacanthoma.
AB  - An 83-year-old man presented with a 1-month history of a rapidly enlarging
      conjunctival mass. On examination, slit lamp biomicroscopy revealed a leukoplakic
      tumour at the temporal limbus. The lesion was excised with cryotherapy
      application to the limbus and conjunctival margins. Histopathology revealed a
      keratoacanthoma (KA). KA typically occurs on sun-exposed areas of the skin.
      Conjunctival KA is very rare, and differentiation between conventional squamous
      cell carcinoma (SCCA) and KA can be challenging. The present case highlights the
      indication for excisional surgery in patients with conjunctival KA using the no
      touch technique, cryotherapy, amniotic membrane and the histopathological
      differentiation between KA and SCCA. 

PMID- 24288391
TI  - Response to the letter by Huisingh and McGewin: Cluster of Urrets-Zavalia
      syndrome: a sequel of toxic anterior segment syndrome.

PMID- 24288392
TI  - Innovations in 3D printing: a 3D overview from optics to organs.
AB  - 3D printing is a method of manufacturing in which materials, such as plastic or
      metal, are deposited onto one another in layers to produce a three dimensional
      object, such as a pair of eye glasses or other 3D objects. This process contrasts
      with traditional ink-based printers which produce a two dimensional object (ink
      on paper). To date, 3D printing has primarily been used in engineering to create
      engineering prototypes. However, recent advances in printing materials have now
      enabled 3D printers to make objects that are comparable with traditionally
      manufactured items. In contrast with conventional printers, 3D printing has the
      potential to enable mass customisation of goods on a large scale and has
      relevance in medicine including ophthalmology. 3D printing has already been
      proved viable in several medical applications including the manufacture of
      eyeglasses, custom prosthetic devices and dental implants. In this review, we
      discuss the potential for 3D printing to revolutionise manufacturing in the same
      way as the printing press revolutionised conventional printing. The applications
      and limitations of 3D printing are discussed; the production process is
      demonstrated by producing a set of eyeglass frames from 3D blueprints. 

PMID- 24288393
TI  - Protection of corneal epithelial stem cells prevents ultraviolet A damage during
      corneal collagen cross-linking treatment for keratoconus.
AB  - BACKGROUND/AIMS: Cross-linking of the cornea is usually carried out at a young
      age as a treatment to manage ectasia. The corneal limbal region contains delicate
      long-lived stem cells, which could potentially be deleteriously affected by
      Ultraviolet A (UV-A) radiation. Damage to these stem cells may not demonstrate as
      a clinical problem for many years subsequent to cross-linking treatment. UV-A
      radiation is known to have potential mutagenic effects upon mammalian DNA and can
      result in cancer. METHODS: Cultured corneal epithelial cells and ex vivo corneal
      tissue were treated with the standard clinical cross-linking protocol for UV-A
      irradiation. 8-hydroxydeoxyguansoine (8-OHdG) and cyclin-dependent kinase
      inhibitor genes (CDKN1A and CDKN2A) were assayed as markers of DNA damage using
      immunohistochemistry, ELISA and quantitative real time PCR. RESULTS: Staining of
      treated limbal tissue demonstrated the presence of 8-OHdG within p63 positive
      basal limbal cells. Levels of 8-OHdG and CDKN1A mRNA were found to be
      significantly increased in cultured corneal epithelial cells and limbal
      epithelial cells but no increase was demonstrated with the use of a polymethyl
      methylacrylate protective cover. CONCLUSIONS: This study provides evidence that
      oxidative nuclear DNA damage can occur through cross-linking in layers of corneal
      epithelial cells at the limbus and that this can be easily prevented by covering
      the limbus.

PMID- 24288394
TI  - Direct comparison of spectral-domain and swept-source OCT in the measurement of
      choroidal thickness in normal eyes.
AB  - OBJECTIVE: To compare spectral-domain optic coherence tomography (SD-OCT) and
      swept-source OCT (SS-OCT) in the study of choroidal thickness (CT) in healthy
      eyes. METHODS: Prospective, cross-sectional, single-centre study. 82 healthy eyes
      of 46 patients were included. In a single session, Topcon 3D-2000 SD-OCT and 1050
      nm SS-OCT prototype devices were used to perform OCT scans using a single line
      protocol. Two masked investigators independently, manually determined 13 CT
      measurements consisting of one subfoveal (SFCT), and six measurements on either
      side of the fovea (nasal and temporal) taken every 500 microns apart. The mean CT
      (MCT) was the mean average of these 13 measurements. RESULTS: SD-OCT was able to
      reproducibly measure the CT in 74.4% of eyes vs 100% with SS-OCT (p<0.05;
      Fisher's Exact test). In those eyes measured by both systems, mean SFCT was 279.4
      +/- 96.9 MUm (range, 84-506) with SD-OCT vs 285.7 +/- 88.9 MUm (range 130-527)
      with SS-OCT (p=0.11; Student's t test paired data). Mean MCT was 243.8 +/- 78.8
      MUm (range 103.6-433.2) with SD-OCT vs 242.2 +/- 81.8 MUm (range 97.6-459) with
      SS-OCT (p=0.64; Student's t test paired data). The difference in SFCT and MCT was
      not statistically significant between both devices. Intraclass correlation
      coefficient was higher than 0.9 interobserver and interdevice measurements. SFCT
      Bland-Altman plots showed 95% interobserver measurement agreement within +/-34
      for SD-OCT, +/-22 for SS-OCT and +/-60 MUm intersystems. CONCLUSIONS: SS-OCT
      permitted accurate identification of the choroido-scleral border in 100% of
      normal eyes, suggesting that SS-OCT was the superior modality for the measurement
      of CT.

PMID- 24288395
TI  - Effects of combination therapy with olmesartan and azelnidipine on serum
      osteoprotegerin in patients with hypertension.
AB  - BACKGROUND: Vascular calcification is a potent predictor of plaque instability
      and cardiac events. Osteoprotegerin (OPG), well-known vascular calcification
      mediator, is a signaling molecule involved in bone remodeling, which has been
      implicated in the regulation of vascular calcification and atherogenesis. The
      purpose of this study was to compare the combination treatments of
      olmesartan/azelnidipine and olmesartan/diuretics on serum bone-related markers in
      patients with essential hypertension. METHODS AND RESULTS: A total of 48 patients
      with hypertension treated with 20 mg olmesartan were randomized to receive
      combination treatment with 16 mg azelnidipine (O/A group) or diuretics (1 mg
      indapamide; O/D group) for 12 months. Osteoprotegerin, matrix metalloproteinase 2
      (MMP-2), and high-sensitive CRP (hs-CRP) were measured after 3 and 12 months of
      treatment. Cardio-ankle vascular index (CAVI) was measured as the arterial
      stiffness using a VaSera CAVI instrument at the same time points. In both groups,
      the systolic and diastolic blood pressure reduction is similar. Serum OPG, MMP-2,
      and hs-CRP were significantly decreased at 12 months in the O/A group (P < .05),
      while there were no significant reductions in the O/D group. CAVI was
      significantly improved at 12 months in both the treatment groups. The improvement
      in CAVI was significantly greater in the O/A group than in the O/D group.
      CONCLUSION: Azelnidipine, but not indapamide, combined with olmesartan, improved
      arterial stiffness and were associated with significant decrease in OPG, MMP-2,
      and hs-CRP concentrations. These results suggest that the beneficial effects of
      the combination treatments of olmesartan/azelnidipine on arterial stiffness are
      mediated by alteration in bone-remodeling and inflammatory markers.

PMID- 24288396
TI  - Reduction of early reperfusion injury with the mitochondria-targeting peptide
      bendavia.
AB  - We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced
      infarction and no-reflow across several experimental models. The purpose of this
      study was to determine the therapeutic timing and mechanism of action that
      underlie Bendavia's cytoprotective property. In rabbits exposed to in vivo
      ischemia/reperfusion (30/180 min), Bendavia administered 20 minutes prior to
      reperfusion (0.05 mg/kg/h, intravenously) reduced myocardial infarct size by ~50%
      when administered for either 1 or 3 hours of reperfusion. However, when Bendavia
      perfusion began just 10 minutes after the onset of reperfusion, the protection
      against infarction and no-reflow was completely lost, indicating that the
      mechanism of protection is occurring early in reperfusion. Experiments in
      isolated mouse liver mitochondria found no discernible effect of Bendavia on
      blocking the permeability transition pore, and studies in isolated heart
      mitochondria showed no effect of Bendavia on respiratory rates. As Bendavia
      significantly lowered reactive oxygen species (ROS) levels in isolated heart
      mitochondria, the ROS-scavenging capacity of Bendavia was compared to well-known
      ROS scavengers using in vitro (cell-free) systems that enzymatically generate
      ROS. Across doses ranging from 1 nmol/L to 1 mmol/L, Bendavia showed no
      discernible ROS-scavenging properties, clearly differentiating itself from
      prototypical scavengers. In conclusion, Bendavia is a promising candidate to
      reduce cardiac injury when present at the onset of reperfusion but not after
      reperfusion has already commenced. Given that both infarction and no-reflow are
      related to increased cellular ROS, Bendavia's protective mechanism of action
      likely involves reduced ROS generation (as opposed to augmented scavenging) by
      endothelial and myocyte mitochondria. 

PMID- 24288397
TI  - Gadoxetic acid-enhanced MRI for T-staging of gallbladder carcinoma: emphasis on
      liver invasion.
AB  - OBJECTIVE: To evaluate the diagnostic performance of gadoxetic acid-enhanced MRI
      with an emphasis on the usefulness of the hepatobiliary phase (HBP) in T-staging
      of gallbladder carcinoma. METHODS: 66 patients with surgically confirmed
      gallbladder carcinoma underwent MRI. Two radiologists independently reviewed two
      sets of gadoxetic acid-enhanced MRI without and with the HBP. Local tumour spread
      was evaluated according to T-staging, and the results were compared with
      pathological findings. The diagnostic performance of two image sets to
      differentiate each T-stage was compared. RESULTS: The sensitivities of MRI with
      the HBP to differentiate T1 vs >= T2 lesions, <= T2 vs >= T3 lesions and <= T3 vs
      T4 lesions were 96.3%, 85.7% and 100% for Observer 1 and 92.6%, 95.2% and 100%
      for Observer 2, respectively (p<0.0001). By adding the HBP, the sensitivities to
      differentiate <= T2 vs >= T3 lesions were increased from 66.7% to 85.7% for
      Observer 1 and from 81.0% to 95.2% for Observer 2, although there was no
      significant difference (p>0.05). The overall accuracies for T-staging were
      increased from 80.3% to 86.4% for Observer 1, a statistically significant degree
      (p=0.046), and from 83.8% to 87.9% for Observer 2 (p>0.05). The k-value for the
      two observers indicated excellent agreement. CONCLUSION: Gadoxetic acid-enhanced
      MRI provided acceptable diagnostic performance for T-staging of gallbladder
      carcinoma. Addition of the HBP aids in the detection of liver invasion. ADVANCES
      IN KNOWLEDGE: In the T-staging of gallbladder carcinoma, gadoxetic acid-enhanced
      MRI with the HBP may enhance detection of liver invasion.

PMID- 24288398
TI  - Paediatric post-septal and pre-septal cellulitis: 10 years' experience at a
      tertiary-level children's hospital.
AB  - OBJECTIVE: To assess the incidence and complications of pre-septal (pre-SC) and
      post-septal (post-SC) cellulitis over 10 years. Pre-SC and post-SC are also known
      as periorbital and orbital cellulitis, respectively. METHODS: Retrospective
      analysis of CT scans. Data included the presence of pre-SC and post-SC, paranasal
      sinus disease (PNS) and complications. RESULTS: Among 125 patients scanned for
      these suspected diagnoses, 67 had both pre-SC and post-SC, 37 had pre-SC and 4
      had post-SC; there were 17 normal scans. 110 patients had PNS. 68/71 (96%)
      patients with post-SC had PNS. Post-SC complications included orbital and/or
      subperiosteal abscess (50/71: 30 medial orbital, 10 superomedial, 3 lateral, 2
      anteromedial, 2 inferomedial, 1 superior, 1 anterosuperior and 1 not specified),
      cavernous sinus thrombosis (CST) (1), superior ophthalmic vein (SOV) thrombosis
      (4) and subdural frontal empyema (2); 1 patient had SOV and CST and subdural
      empyema. CONCLUSION: 71/125 (57%) patients had post-SC. 50/125 (40%) patients
      imaged for pre-SC/post-SC had orbital abscess; 44/50 (88%) of these involved the
      medial orbit. Patients can develop solely superior or inferior abscesses that are
      difficult to identify by axial imaging alone, hence coronal reformatted imaging
      is essential. 5/125 (4%) patients developed major complications
      (SOV/CST/empyema), hence imaging review of the head and cavernous sinus region is
      essential. A diagnosis of post-SC on CT should alert the radiologist because this
      diagnosis can be associated with an increased incidence (5/71, 7%) of
      complications. ADVANCES IN KNOWLEDGE: We recommend that all patients with a
      suspected diagnosis of post-SC should undergo CT scan (post-contrast orbits and
      post-contrast head, with multiplanar reformats and a careful review of the SOV
      and the cavernous sinus). Particular attention should be paid to exclude
      intracranial complications including subdural empyema and cerebral abscess. As
      soon as a diagnosis of post-SC is made, in addition to informing the referring
      clinical team, urgent opinion should be sought from ear, nose and throat (ENT),
      neurology and ophthalmology with a view to urgently drain of the paranasal
      sinuses'.

PMID- 24288399
TI  - Particle therapy using carbon ions or protons as a definitive therapy for
      patients with primary sacral chordoma.
AB  - OBJECTIVE: This study retrospectively evaluated the efficacy and toxicity of
      particle therapy using carbon ions or protons for primary sacral chordomas.
      METHODS: We evaluated 23 patients with primary sacral chordoma treated with
      carbon ion therapy (CIT) or proton therapy (PT) between July 2005 and June 2011
      at the Hyogo Ion Beam Medical Center, Hyogo, Japan. The median patient age was 72
      years. 14 patients were treated with 70.4 Gy equivalents (GyE) in 16 fractions
      and 9 were treated with 70.4 GyE in 32 fractions. CIT was used for 16 patients,
      and PT was used for 7 patients. RESULTS: The median follow-up period was 38
      months. At 3 years, local control (LC), overall survival (OS) and progression
      free survival (PFS) for all patients were 94%, 83% and 68%, respectively. The log
      rank test revealed that male sex was significantly related to better PFS
      (p=0.029). No other factors, including dose fractionation and ion type, were
      significant for LC, OS or PFS. In nine patients, >= Grade 3 acute dermatitis was
      observed, and >= Grade 3 late toxicities were observed in nine patients. The 32
      fraction protocol reduced severe toxicities in both the acute and late phases
      compared with the 16-fraction protocol. CONCLUSION: Particle therapy for patients
      with sacral chordoma showed favourable LC and OS. Severe toxicities were
      successfully reduced by modifying the dose fractionation and treatment planning
      in the later treatment era. Thus, this therapeutic modality should be considered
      useful and safe. ADVANCES IN KNOWLEDGE: This is the first study including both
      CIT and PT for sacral chordomas.

PMID- 24288400
TI  - Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and
      children: from research into clinical practice.
AB  - Although post-mortem MRI (PMMR) was proposed as an alternative to conventional
      autopsy more than a decade ago, the lack of systematic validation has limited its
      clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with
      ancillary investigations has now been shown to be as accurate as conventional
      autopsy in foetuses, newborns and infants and is particularly useful for
      cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR
      provides a permanent three-dimensional auditable record, with accurate estimation
      of internal organ volumes. MIA is becoming highly acceptable to parents and
      professionals, and there is widespread political support and public interest in
      its clinical implementation in the UK. In the short to medium term, it is
      desirable that a supraregional network of specialist centres should be
      established to provide this service within the current National Health Service
      framework. 

PMID- 24288401
TI  - Evaluation of internal target volume in patients undergoing image-guided
      intensity modulated adjuvant radiation for gastric cancers.
AB  - OBJECTIVE: To evaluate three-dimensional (3D) displacements of gastric remnant
      during adjuvant radiation. METHODS: From January 2011 to September 2012, patients
      undergoing adjuvant image-guided intensity-modulated radiation on tomotherapy
      were included. Megavoltage CT (MVCT) data sets from daily treatment were
      coregistered with Day 1 MVCT. Residual stomach remnant was delineated on the data
      set, while the remaining were blinded to previous day contours. Gastric volume
      and centre of mass (COM) were determined for all data sets. The 3D deviation of
      COM was calculated for each fraction. Mean 3D and standard deviation (SD) were
      calculated for each patient and study population, and a 95% confidence interval
      (CI) was determined. Also, systematic and random errors for patient population
      and internal target volume (ITV) margin were calculated using the van Herk
      formula. RESULTS: There were 119 images available for 15 patients. Mean volume of
      remnant was 319 cm(3) (146-454 cm(3)). Gastric remnant expanded in different
      directions with no specific directional expansion. Average deviations in
      mediolateral, superoinferior and anteroposterior directions were 9 mm (3-25 mm;
      SD, 5 mm), 6 mm (3-16 mm; SD, 4 mm) and 5 mm (1-10 mm; SD, 3 mm), respectively,
      with 95% CI of 18, 15 and 11 mm, and ITV margins of 19.2, 13.5 and 7.8 mm,
      respectively. CONCLUSION: There is large variation in gastric remnant volume
      during the course of radiation. Large displacements observed in the present study
      necessitate the need to investigate adaptive techniques for optimizing intensity
      modulated radiotherapy (IMRT) delivery. ADVANCES IN KNOWLEDGE: An adaptive
      strategy needs to be developed to optimize IMRT delivery for adjuvant gastric
      irradiation.

PMID- 24288402
TI  - Co-registration of cone beam CT and planning CT in head and neck IMRT dose
      estimation: a feasible adaptive radiotherapy strategy.
AB  - OBJECTIVE: To investigate if cone beam CT (CBCT) can be used to estimate the
      delivered dose in head and neck intensity-modulated radiotherapy (IMRT). METHODS:
      15 patients (10 without replan and 5 with replan) were identified
      retrospectively. Weekly CBCT was co-registered with original planning CT.
      Original high-dose clinical target volume (CTV1), low-dose CTV (CTV2), brainstem,
      spinal cord, parotids and external body contours were copied to each CBCT and
      modified to account for anatomical changes. Corresponding planning target volumes
      (PTVs) and planning organ-at-risk volumes were created. The original plan was
      applied and calculated using modified per-treatment volumes on the original CT.
      Percentage volumetric, cumulative (planned dose delivered prior to CBCT +
      adaptive dose delivered after CBCT) and actual delivered (summation of weekly
      adaptive doses) dosimetric differences between each per-treatment and original
      plan were calculated. RESULTS: There was greater volumetric change in the
      parotids with an average weekly difference of between -4.1% and -27.0% compared
      with the CTVs/PTVs (-1.8% to -5.0%). The average weekly cumulative dosimetric
      differences were as follows: CTV/PTV (range, -3.0% to 2.2%), ipsilateral parotid
      volume receiving >=26 Gy (V26) (range, 0.5-3.2%) and contralateral V26 (range,
      1.9-6.3%). In patients who required replan, the average volumetric reductions
      were greater: CTV1 (-2.5%), CTV2 (-6.9%), PTV1 (-4.7%), PTV2 (-11.5%),
      ipsilateral (-10.4%) and contralateral parotids (-12.1%), but did not result in
      significant dosimetric changes. CONCLUSION: The dosimetric changes during head
      and neck simultaneous integrated boost IMRT do not necessitate adaptive
      radiotherapy in most patients. ADVANCES IN KNOWLEDGE: Our study shows that CBCT
      could be used for dose estimation during head and neck IMRT.

PMID- 24288403
TI  - MRI in necrotizing fasciitis of the extremities.
AB  - Necrotizing fasciitis is a life-threatening soft-tissue infection of bacterial
      origin, which involves mainly the deep fascia. Early recognition of this
      condition may be hampered by the uncommon nature of the disease and non
      specificity of initial clinical signs and symptoms in less fulminant cases,
      making the role of imaging important. MRI is the most useful imaging modality in
      the diagnosis of necrotizing fasciitis. The presence of thick (>3 mm)
      hyperintense signal in the deep fascia (particularly intermuscular fascia) on fat
      suppressed T2 weighted or short tau inversion-recovery images is an important
      marker for necrotizing fasciitis. Contrast enhancement of the thickened necrotic
      fascia can be variable, with a mixed-pattern of enhancement being more commonly
      encountered. Involvement of multiple musculofascial compartments increases the
      likelihood of necrotizing fasciitis. It is important to remember that T2
      hyperintense signal in the deep fascia is not specific to necrotizing fasciitis
      and can also be seen in cases such as non-infective inflammatory fasciitis or
      muscle tear. In this pictorial essay, we aim to review the MRI findings in
      necrotizing fasciitis, discuss its limitations and pitfalls and identify
      differentiating features from non-necrotizing soft-tissue infections, such as
      cellulitis and infective myositis/pyomyositis, conditions which may clinically
      mimic necrotizing fasciitis.

PMID- 24288404
TI  - The TRIMming on an erythroid repressor complex.

PMID- 24288405
TI  - No immunosurveillance in human IL-10R deficiency.

PMID- 24288406
TI  - Clearing the path for MPN therapy monitoring.

PMID- 24288407
TI  - Causal role for JAK2 V617F in thrombosis.

PMID- 24288408
TI  - Bad (or good) things come in small packages.

PMID- 24288409
TI  - CXCL1 excess stops neutrophils in their tracks.

PMID- 24288410
TI  - Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective
      prophylaxis?

PMID- 24288411
TI  - MYSM1 is mutated in a family with transient transfusion-dependent anemia, mild
      thrombocytopenia, and low NK- and B-cell counts.

PMID- 24288412
TI  - Rare complete loss of function provides insight into a pleiotropic genome-wide
      association study locus.

PMID- 24288413
TI  - Time-dependent degradation and tissue factor addition mask the ability of
      platelet polyphosphates in activating factor XII-mediated coagulation.

PMID- 24288415
TI  - Logistic Regression with Multiple Random Effects: A Simulation Study of
      Estimation Methods and Statistical Packages.
AB  - Several statistical packages are capable of estimating generalized linear mixed
      models and these packages provide one or more of three estimation methods:
      penalized quasi-likelihood, Laplace, and Gauss-Hermite. Many studies have
      investigated these methods' performance for the mixed-effects logistic regression
      model. However, the authors focused on models with one or two random effects and
      assumed a simple covariance structure between them, which may not be realistic.
      When there are multiple correlated random effects in a model, the computation
      becomes intensive, and often an algorithm fails to converge. Moreover, in our
      analysis of smoking status and exposure to anti-tobacco advertisements, we have
      observed that when a model included multiple random effects, parameter estimates
      varied considerably from one statistical package to another even when using the
      same estimation method. This article presents a comprehensive review of the
      advantages and disadvantages of each estimation method. In addition, we compare
      the performances of the three methods across statistical packages via simulation,
      which involves two- and three-level logistic regression models with at least
      three correlated random effects. We apply our findings to a real dataset. Our
      results suggest that two packages-SAS GLIMMIX Laplace and SuperMix Gaussian
      quadrature-perform well in terms of accuracy, precision, convergence rates, and
      computing speed. We also discuss the strengths and weaknesses of the two packages
      in regard to sample sizes.

PMID- 24288416
TI  - Glycosyl Thioimidates as Versatile Building Blocks for Organic Synthesis.
AB  - This review discusses the synthesis and application of glycosyl thioimidates in
      chemical glycosylation and oligosaccharide assembly. Although glycosyl
      thioimidates include a broad range of compounds, the discussion herein centers on
      S-benzothiazolyl (SBaz), S-benzoxazolyl (SBox), S-thiazolinyl (STaz), and S
      benzimidazolyl (SBiz) glycosides. These heterocyclic moieties have recently
      emerged as excellent anomeric leaving groups that express unique characteristics
      for highly diastereoselective glycosylation and help to provide the streamlined
      access to oligosaccharides.

PMID- 24288417
TI  - GENDER AND THE HEALTH BENEFITS OF EDUCATION.
AB  - Does education improve health more for one sex than the other? We develop a
      theory of resource substitution which implies that education improves health more
      for women than men. Data from a 1995 survey of U.S. adults with follow-ups in
      1998 and 2001 support the hypothesis. Physical impairment decreases more for
      women than for men as the level of education increases. The gender gap in
      impairment essentially disappears among people with a college degree. Latent
      growth SEM vectors also show that among the college educated, men's and women's
      life course patterns of physical impairment do not differ significantly.

PMID- 24288419
TI  - Multiscale Community Blockmodel for Network Exploration.
AB  - Real world networks exhibit a complex set of phenomena such as underlying
      hierarchical organization, multiscale interaction, and varying topologies of
      communities. Most existing methods do not adequately capture the intrinsic
      interplay among such phenomena. We propose a nonparametric Multiscale Community
      Blockmodel (MSCB) to model the generation of hierarchies in social communities,
      selective membership of actors to subsets of these communities, and the resultant
      networks due to within- and cross-community interactions. By using the nested
      Chinese Restaurant Process, our model automatically infers the hierarchy
      structure from the data. We develop a collapsed Gibbs sampling algorithm for
      posterior inference, conduct extensive validation using synthetic networks, and
      demonstrate the utility of our model in real-world datasets such as predator-prey
      networks and citation networks.

PMID- 24288418
TI  - An Empirical Analysis of the Impact of Recruitment Patterns on RDS Estimates
      among a Socially Ordered Population of Female Sex Workers in China.
AB  - Respondent-driven sampling (RDS) is a method for recruiting "hidden" populations
      through a network-based, chain and peer referral process. RDS recruits hidden
      populations more effectively than other sampling methods and promises to generate
      unbiased estimates of their characteristics. RDS's faithful representation of
      hidden populations relies on the validity of core assumptions regarding the
      unobserved referral process. With empirical recruitment data from an RDS study of
      female sex workers (FSWs) in Shanghai, we assess the RDS assumption that
      participants recruit nonpreferentially from among their network alters. We also
      present a bootstrap method for constructing the confidence intervals around RDS
      estimates. This approach uniquely incorporates real-world features of the
      population under study (e.g., the sample's observed branching structure). We then
      extend this approach to approximate the distribution of RDS estimates under
      various peer recruitment scenarios consistent with the data as a means to
      quantify the impact of recruitment bias and of rejection bias on the RDS
      estimates. We find that the hierarchical social organization of FSWs leads to
      recruitment biases by constraining RDS recruitment across social classes and
      introducing bias in the RDS estimates.

PMID- 24288420
TI  - A Semiparametric Change-Point Regression Model for Longitudinal Observations.
AB  - Many longitudinal studies involve relating an outcome process to a set of
      possibly time-varying covariates, giving rise to the usual regression models for
      longitudinal data. When the purpose of the study is to investigate the covariate
      effects when experimental environment undergoes abrupt changes or to locate the
      periods with different levels of covariate effects, a simple and easy-to
      interpret approach is to introduce change-points in regression coefficients. In
      this connection, we propose a semiparametric change-point regression model, in
      which the error process (stochastic component) is nonparametric and the baseline
      mean function (functional part) is completely unspecified, the observation times
      are allowed to be subject-specific, and the number, locations and magnitudes of
      change-points are unknown and need to be estimated. We further develop an
      estimation procedure which combines the recent advance in semiparametric analysis
      based on counting process argument and multiple change-points inference, and
      discuss its large sample properties, including consistency and asymptotic
      normality, under suitable regularity conditions. Simulation results show that the
      proposed methods work well under a variety of scenarios. An application to a real
      data set is also given.

PMID- 24288421
TI  - A nonparametric spatial model for periodontal data with non-random missingness.
AB  - Periodontal disease progression is often quantified by clinical attachment level
      (CAL) defined as the distance down a tooth's root that is detached from the
      surrounding bone. Measured at 6 locations per tooth throughout the mouth
      (excluding the molars), it gives rise to a dependent data set-up. These data are
      often reduced to a one-number summary, such as the whole mouth average or the
      number of observations greater than a threshold, to be used as the response in a
      regression to identify important covariates related to the current state of a
      subject's periodontal health. Rather than a simple one-number summary, we set
      forward to analyze all available CAL data for each subject, exploiting the
      presence of spatial dependence, non-stationarity, and non-normality. Also, many
      subjects have a considerable proportion of missing teeth which cannot be
      considered missing at random because periodontal disease is the leading cause of
      adult tooth loss. Under a Bayesian paradigm, we propose a nonparametric flexible
      spatial (joint) model of observed CAL and the location of missing tooth via
      kernel convolution methods, incorporating the aforementioned features of CAL data
      under a unified framework. Application of this methodology to a data set
      recording the periodontal health of an African-American population, as well as
      simulation studies reveal the gain in model fit and inference, and provides a new
      perspective into unraveling covariate-response relationships in presence of
      complexities posed by these data.

PMID- 24288422
TI  - The Nonlinear Relationship between Education and Mortality: An Examination of
      Cohort, Race/Ethnic, and Gender Differences.
AB  - Researchers investigating the relationship between education and mortality in
      industrialized countries have consistently shown that higher levels of education
      are associated with decreased mortality risk. The shape of the education
      mortality relationship and how it varies by demographic group have been examined
      less frequently. Using the U.S. National Health Interview Survey-Linked Mortality
      Files, which link the 1986 through 2004 NHIS to the National Death Index through
      2006, we examine the shape of the education-mortality curve by cohort,
      race/ethnicity, and gender. Whereas traditional regression models assume a
      constrained functional form for the dependence of education and mortality, in
      most cases semiparametric models allow us to more accurately describe how the
      association varies by cohort, both between and within race/ethnic and gender
      subpopulations. Notably, we find significant changes over time in both the shape
      and the magnitude of the education-mortality gradient across cohorts of women and
      white men, but little change among younger cohorts of black men. Such insights
      into demographic patterns in education and mortality can ultimately help increase
      life expectancies.

PMID- 24288423
TI  - Solid-State Densification of Spun-Cast Self-Assembled Monolayers for Use in Ultra
      Thin Hybrid Dielectrics.
AB  - Ultra-thin self-assembled monolayer (SAM)-oxide hybrid dielectrics have gained
      significant interest for their application in low-voltage organic thin film
      transistors (OTFTs). A [8-(11-phenoxy-undecyloxy)-octyl]phosphonic acid (PhO-19
      PA) SAM on ultrathin AlOx (2.5 nm) has been developed to significantly enhance
      the dielectric performance of inorganic oxides through reduction of leakage
      current while maintaining similar capacitance to the underlying oxide structure.
      Rapid processing of this SAM in ambient conditions is achieved by spin coating,
      however, as-cast monolayer density is not sufficient for dielectric applications.
      Thermal annealing of a bulk spun-cast PhO-19-PA molecular film is explored as a
      mechanism for SAM densification. SAM density, or surface coverage, and order are
      examined as a function of annealing temperature. These SAM characteristics are
      probed through atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), and near edge X-ray absorption fine structure spectroscopy (NEXAFS). It is
      found that at temperatures sufficient to melt the as-cast bulk molecular film,
      SAM densification is achieved; leading to a rapid processing technique for high
      performance SAM-oxide hybrid dielectric systems utilizing a single wet processing
      step. To demonstrate low-voltage devices based on this hybrid dielectric (with
      leakage current density of 7.7*10-8 A cm-2 and capacitance density of 0.62 uF cm
      2 at 3 V), pentacene thin-film transistors (OTFTs) are fabricated and yield sub 2
      V operation and charge carrier mobilites of up to 1.1 cm2 V-1 s-1.

PMID- 24288424
TI  - Association of TAP gene polymorphisms and risk of cervical intraepithelial
      neoplasia.
AB  - BACKGROUND: Transporter associated with antigen processing (TAP) is responsible
      for peptide loading onto class I major histocompatibility complex (MHC-I)
      molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and
      contributes to successful eradication of HPV. TAP polymorphisms could have an
      important impact on the course of HPV infection. OBJECTIVE: The aim of this study
      is to evaluate the association between five TAP gene polymorphisms and the risk
      of CIN. Methods. This case-control study investigated five common TAP
      polymorphisms in TAP1 (1341 and 2254) and TAP2 (1135, 1693, and 1993) in 616
      women with CIN and 206 controls. Associations between gene polymorphisms and risk
      of CIN were analysed by univariate and multivariable models. The combined effect
      of the five TAP gene polymorphisms on the risk for CIN was investigated by
      haplotype analysis. RESULTS: No significant difference in genotype distribution
      of the five TAP polymorphisms was observed in women with CIN and controls.
      Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP
      polymorphisms t1135-t1341-t1693-t1993-t2254) had a significantly lower risk for
      CIN, compared to women with the haplotype wt-wt-wt-wt-wt (P = 0.006; OR 0.5 [0.35
      0.84]). CONCLUSION: Identification of this haplotype combination could be used to
      identify women, less susceptible for development of CIN following HPV infection.

PMID- 24288425
TI  - Micropapillary pattern at the invasive front and its association with
      unresectable colorectal carcinomas.
AB  - Unresectable colorectal carcinomas (CRCs) as considered incurable even if the
      primary tumors and the metastatic ones can undergo resection are correlated with
      poor prognosis. We evaluated the association between micropapillary pattern at
      the invasive front and unresectable CRCs. Thirty-four out of 264 (12.9%) CRC
      patients with stages III and IV were unresectable cases. The patients with
      unresectable CRCs had significantly worse survival than those with resectable
      CRCs (P < 0.001). Micropapillary pattern was evident in 12 (4.5%) out of 264
      cases. This pattern was observed in 6 of 34 (17.6%) unresectable CRCs and in 6 of
      230 (2.6%) resectable cases (P = 0.002). Unresectable CRCs revealed more
      frequently deeper invasion (odds ratio (OR), 1.175; 95% confidence interval (CI),
      1.113-1.241), lymph node metastasis (OR, 2.356; 95% CI, 1.132-4.905), and
      presence of micropapillary pattern at the invasive front (OR, 8.000; 95% CI,
      2.415-26.504) as compared to resectable cases. By multivariable logistic
      regression analysis, only micropapillary pattern was shown to be an independent
      predictor of unresectable CRCs (OR, 9.451; 95% CI, 2.468-36.196; P < 0.001). In
      conclusion, micropapillary pattern at the invasive front is associated with
      unresectable CRCs, and detection of it could help identify unresectable CRC
      cases. 

PMID- 24288426
TI  - The salivary beta-HEX A% index as an excellent marker of periodontitis in smoking
      alcohol-dependent persons.
AB  - BACKGROUND: Severe periodontitis leading to tooth loss is found in 5-15% of most
      populations worldwide. AIM: The applicability of salivary beta -hexosaminidase
      (beta-HEX A%, percentage of beta-HEX A isoenzyme to total beta-HEX) and beta-HEX
      B% (beta-HEX B/beta-HEX) indexes was investigated as a possible marker of
      periodontitis. METHODS: Thirty three alcohol-dependent smokers (AS) and 32
      healthy controls (C) were enrolled in the study. The activity of beta-HEX was
      measured spectrophotometrically. RESULTS: beta-HEX A% was significantly higher
      and beta-HEX B% was lower in AS than in C group. We found a significant
      correlation between beta-HEX A% and gingival index (GI) and an inverse
      correlation between beta-HEX A% and salivary flow (SF), in all groups. Salivary
      beta-HEX A% index in smoking alcoholics at 0.23 had excellent sensitivity (96%)
      and specificity (91%); the AUC for beta-HEX A% was high (0.937). There were no
      correlations between amount/duration-time of alcohol drinking/smoking and beta
      HEX A% or beta-HEX B%. We found significant correlations between the time period
      of denture wearing and GI, papilla bleeding index (PBI), and decayed missing
      filled teeth index (DMFT) and between GI and the amount of smoked cigarettes per
      day. CONCLUSION: Bad periodontal state was most likely due to the nicotine
      dependence. Salivary beta-HEX A% is a promising excellent marker for the
      diagnosis of periodontitis.

PMID- 24288427
TI  - Mutation of NPM1 and FLT3 genes in acute myeloid leukemia and their association
      with clinical and immunophenotypic features.
AB  - BACKGROUND: Mutations in NPM1 and FLT3 genes represent the most frequent genetic
      alterations and important diagnostic and prognostic indicators in patients with
      acute myeloid leukemia (AML). OBJECTIVE: We investigated the prevalence and
      clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo
      AML including adults and children. RESULTS: NPM1 mutation was found in 21% and
      FLT3 mutation in 25% of the AML patients. Thirteen (8%) samples were positive for
      both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher
      frequency of NPM1 mutation than children (25.8% versus 8.8%; P = 0.02). Further,
      NPM1 mutation was found to be more frequent in patients above 45 years of age (P
      = 0.02). NPM1 mutation was significantly associated with higher platelet count (P
      = 0.05) and absence of hepatosplenomegaly (P = 0.01), while FLT3/ITD mutation was
      associated with higher white blood count (P = 0.01). Immunophenotypically, NPM1
      mutation was associated with the lack of CD34 (P < 0.001) and HLD-DR expression
      (P < 0.001), while FLT3/ITD mutation was positively associated with the
      expression of CD7 (P = 0.04). No correlation was found between NPM1 mutation and
      fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely
      associated with AML/ETO fusion gene (P = 0.04). CONCLUSIONS: The results suggest
      that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD
      mutations present further insight into the molecular mechanism of leukemogenesis.

PMID- 24288428
TI  - Rapid and inexpensive screening of genomic copy number variations using a novel
      quantitative fluorescent PCR method.
AB  - Detection of human microdeletion and microduplication syndromes poses significant
      burden on public healthcare systems in developing countries. With genome-wide
      diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches
      are preferred. However, their reproducibility depends on equally efficient
      amplification using a number of target and control primers. To address this, the
      recently described technique called Microdeletion/Microduplication Quantitative
      Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by
      quantifying DNA amplification in an internally controlled PCR reaction. Here, we
      confirm its utility in the detection of eight human microdeletion syndromes,
      including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with
      100% sensitivity and 100% specificity. We present selection, design, and
      performance evaluation of detection primers using variety of approaches. We
      conclude that MQF-PCR is an easily adaptable method for detection of human
      pathological chromosomal aberrations. 

PMID- 24288429
TI  - Are breast cancer molecular classes predictive of survival in patients with long
      follow-up?
AB  - In this study we investigate the clinical outcomes of 305 breast cancer (BC)
      patients, aged 55 years or younger, with long follow-up and according to
      intrinsic subtypes. The cohort included 151 lymph node negative (LN-) and 154
      lymph node positive (LN+) patients. Luminal A tumors were mainly LN-, well
      differentiated, and of stage I; among them AR was an indicator of good prognosis.
      Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and
      nodal metastases as well as higher proliferation status and stage. Among luminal
      tumors, those PR positive and vimentin negative showed a longer survival. HER2
      positive nonluminal and TN patients showed a poorer outcome, with BC-specific
      death mostly occurring within 5 and 10 years. Only luminal tumor patients
      underwent BC death over 10 years. When patients were divided in to LN- and LN+ no
      differences in survival were observed in the luminal subgroups. LN- patients have
      good survival even after 20 years of follow-up (about 75%), while for LN+
      patients survival at 20 years (around 40%) was comparable to HER2-positive
      nonluminal and TN groups. In conclusion, in our experience ER-positive breast
      tumors are better divided by classical clinical stage than molecular
      classification, and they need longer clinical follow-up especially in cases with
      lymph node involvement.

PMID- 24288430
TI  - Is human papillomavirus associated with prostate cancer survival?
AB  - The role of human papillomavirus (HPV) in prostate carcinogenesis is highly
      controversial: some studies suggest a positive association between HPV infection
      and an increased risk of prostate cancer (PCa), whereas others do not reveal any
      correlation. In this study, we investigated the prognostic impact of HPV
      infection on survival in 150 primary PCa patients. One hundred twelve (74.67%)
      patients had positive expression of HPV E7 protein, which was evaluated in tumour
      tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV
      infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV
      positive cancer patients showed worse overall survival (OS) (median 4.59 years)
      compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate
      analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading (P = 0.002),
      and HPV status (P = 0.034) were independent prognostic factors for OS. In our
      cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an
      association between HPV infection and PCa survival. In the debate about the
      oncogenic activity of HPV in PCa, our results further confirm the need for
      additional studies to clarify the possible role of HPV in prostate
      carcinogenesis.

PMID- 24288431
TI  - Serum levels of selected Th17 and Th22 cytokines in psoriatic patients.
AB  - INTRODUCTION: Psoriasis is a T cell-mediated inflammatory disease in which
      pathogenesis T helper (Th) lymphocytes (Th1, Th17, and Th22) play an important
      role. The aim of the study was to assess the serum levels of some cytokines
      involved in the Th17 and Th22 responses in psoriatic patients. MATERIAL AND
      METHODS: The study comprised 60 psoriatic patients and 30 healthy controls. In
      the serum collected from psoriatic patients and healthy controls, the
      concentrations of IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 were examined with
      ELISA kits. Severity of psoriatic skin lesions was assessed by means of PASI,
      BSA, and PGA scores. RESULTS: IL-6, IL-20, and IL-22 concentrations were
      significantly higher in psoriatic patients in comparison with the control group.
      The positive correlations between the concentrations of IL-22 and IL-20 and
      severity of psoriasis assessed with PASI and BSA scores as well as IL-17 and PASI
      score were found. There was also a positive correlation between IL-23 and IL-17
      concentrations. CONCLUSIONS: Results of the conducted studies suggest that Th22
      response may contribute to the skin and systemic inflammatory disease in
      psoriasis. It seems that early identification of soluble biomarkers and
      initiation of well-matched treatment may prevent exacerbation and progression of
      psoriasis.

PMID- 24288432
TI  - Association of a FGFR-4 gene polymorphism with bronchopulmonary dysplasia and
      neonatal respiratory distress.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common chronic lung
      disease of premature birth, characterized by impaired alveolar development and
      inflammation. Pathomechanisms contributing to BPD are poorly understood. However,
      it is assumed that genetic factors predispose to BPD and other pulmonary diseases
      of preterm neonates, such as neonatal respiratory distress syndrome (RDS). For
      association studies, genes upregulated during alveolarization are major
      candidates for genetic analysis, for example, matrix metalloproteinases (MMPs)
      and fibroblast growth factors (FGFs) and their receptors (FGFR). OBJECTIVE:
      Determining genetic risk variants in a Caucasian population of premature neonates
      with BPD and RDS. Methods. We genotyped 27 polymorphisms within 14 candidate
      genes via restriction fragment length polymorphism (RFLP): MMP-1, -2, -9, and 
      12, -16, FGF receptors 2 and 4, FGF-2, -3, -4, -7, and -18, Signal-Regulatory
      Protein alpha (SIRPA) and Thyroid Transcription Factor-1 (TTF-1). RESULTS: Five
      single nucleotide polymorphisms (SNPs) in MMP-9, MMP-12, FGFR-4, FGF-3, and FGF-7
      are associated (P < 0.05) with RDS, defined as surfactant application within the
      first 24 hours after birth. One of them, in FGFR-4 (rs1966265), is associated
      with both RDS (P = 0.003) and BPD (P = 0.023). CONCLUSION: rs1966265 in FGF
      receptor 4 is a possible genetic key variant in alveolar diseases of preterm
      newborns.

PMID- 24288433
TI  - Association of functional VKORC1 promoter polymorphism with occurrence and
      clinical aspects of ischemic stroke in a Greek population.
AB  - Genetic factors are considered to play an important role in determining the
      susceptibility to the occurrence, clinical course, and functional outcome of an
      acute ischemic stroke (IS). Undercarboxylation of specific vitamin K-dependent
      proteins, due to genetic polymorphisms of VKORC1, can affect both vascular
      calcification and thrombogenicity. We sought to determine the association of
      VKORC1 -1639G > A polymorphism with IS incidence, age of onset, severity of
      disease, and functional outcome after an acute IS. VKORC1 -1639G > A polymorphism
      was determined in 145 consecutive patients with first ever IS and 145 age- and
      sex-matched control subjects of Greek Caucasian origin using PCR-RFLP. Stroke
      severity and functional outcome were assessed on admission and at one month after
      stroke, respectively. Frequency of VKORC1 -1639G > A genotypes did not differ
      between IS patients and controls (OR = 1.12, P = 0.51). Moreover, carriage of the
      A allele was not associated with age of stroke onset, severity of disease
      (Scandinavian stroke scale score 32.2 versus 32.9, resp., P = 0.96), or poor
      outcome at 1 month post-stroke (52.9 versus 64.4%, resp., P = 0.31). In
      conclusion, VKORC1 -1639G > A polymorphism is not a genetic determinant of IS
      occurrence, age of onset, severity, or functional outcome of disease in a Greek
      population. 

PMID- 24288434
TI  - The Pursuit of Happiness in China: Individualism, Collectivism, and Subjective
      Well-Being during China's Economic and Social Transformation*
AB  - This paper examines the consequences of China's dramatic socioeconomic and
      political transformations for individual subjective well-being (SWB) from 1990 to
      2007. Although many still consider China to be a collectivist country, and some
      scholars have argued that collectivist factors would be important predictors of
      individual well-being in such a context, our analysis demonstrates that the
      Chinese are increasingly prioritizing individualist factors in assessments of
      their own happiness and life satisfaction thus substantiating descriptions of
      their society as increasingly individualistic. While the vast majority of quality
      of life studies have focused on Westerners, this study contributes findings from
      the unique cultural context of China. Moreover, concentration on this particular
      period in Chinese history offers insight into the relationship between SWB and
      rapid socioeconomic and political change.

PMID- 24288436
TI  - Is Markhamia lutea's abundance determined by animal foraging?
AB  - Understanding the determinants of tropical forest tree richness and spatial
      distribution is a central goal of forest ecology; however, the role of
      herbivorous mammals has received little attention. Here we explore the potential
      for red colobus monkeys (Procolobus rufomitratus) to influence the abundance of
      Markhamia lutea trees in a tropical forest by feeding extensively on the tree's
      flowers, such that this tree population is not able to regularly set fruit. Using
      14 years of data from Kibale National Park, Uganda, we quantify M. lutea flower
      and fruit production. Similarly, using 21 years of data, we quantify temporal
      changes in the abundance of stems in size classes from 1 m tall and above. Our
      analyses demonstrate that M. lutea is rarely able to produce fruit and that this
      corresponds to a general decline in its abundance across all size classes.
      Moreover, using 7 years of feeding records, we demonstrate that red colobus feed
      on M. lutea, consuming large amounts of leaf and flower buds whenever they were
      available, suggesting that this behavior limits fruit production. Therefore, we
      suggest that red colobus are presently important for structuring the distribution
      and abundance of M. lutea in Kibale. This dynamic raises the intriguing question
      of how a large M. lutea population was able to originally establish. There is no
      evidence of a change in red colobus population size; however, if this old-growth
      forest is in a non-equilibrium state, M. lutea may have become established when
      red colobus ate a different diet.

PMID- 24288437
TI  - Examining the Quality of Adolescent-Parent Relationships Among Chilean Families.
AB  - The purpose of this study was to examine if adolescents reports of warm and harsh
      parenting practices by their mothers and fathers varied as a function of
      demographic, youth and their mothers or mother figures' individual and family
      characteristics. Data are from 707 community-dwelling adolescents (mean age=14,
      SD=1.4) and their mothers or mother figures in Santiago, Chile. Having a warmer
      relationship with both parents was inversely associated with the adolescents' age
      and positively associated with adolescents' family involvement and parental
      monitoring. Both mothers' and fathers' harsh parenting were positively associated
      with adolescent externalizing behaviors and being male and inversely associated
      with youth autonomy and family involvement. These findings suggest that net of
      adolescent developmental emancipation and adolescent behavioral problems,
      positive relationships with parents, especially fathers, may be nurtured through
      parental monitoring and creation of an interactive family environment, and can
      help to foster positive developmental outcomes.

PMID- 24288435
TI  - Are Internet use and video-game-playing addictive behaviors? Biological, clinical
      and public health implications for youths and adults.
AB  - Internet use and video-game playing are experiencing rapid growth among both
      youth and adult populations. Research suggests that a minority of users
      experience symptoms traditionally associated with substance-related addictions.
      Mental health professionals, policy makers and the general public continue to
      debate the issue of Internet addiction (IA) and problematic video-game playing
      (PVG). This review identifies existing studies into the clinical and biological
      characteristics of these disorders that may help guide decisions as to whether or
      not IA and PVG should be grouped together with substance use disorders (SUDs).

PMID- 24288438
TI  - Multibody graph transformations and analysis: Part I: Tree topology systems.
AB  - This two-part paper uses graph transformation methods to develop methods for
      partitioning, aggregating, and constraint embedding for multibody systems. This
      first part focuses on tree-topology systems and reviews the key notion of spatial
      kernel operator (SKO) models for such systems. It develops systematic and
      rigorous techniques for partitioning SKO models in terms of the SKO models of the
      component subsystems based on the path-induced property of the component
      subgraphs. It shows that the sparsity structure of key matrix operators and the
      mass matrix for the multibody system can be described using partitioning
      transformations. Subsequently, the notions of node contractions and subgraph
      aggregation and their role in coarsening graphs are discussed. It is shown that
      the tree property of a graph is preserved after subgraph aggregation if and only
      if the subgraph satisfies an aggregation condition. These graph theory ideas are
      used to develop SKO models for the aggregated tree multibody systems.

PMID- 24288439
TI  - The influence of oral bacteria on epithelial cell migration in vitro.
AB  - Oral ulcerations often arise as a side effect from chemo- and radiation therapy.
      In a previous clinical study, Porphyromonas gingivalis was identified as a
      positive predictor for oral ulcerations after hematopoetic stem cell
      transplantation, possibly incriminating P. gingivalis in delayed healing of the
      ulcerations. Therefore, it was tested whether P. gingivalis and its secreted
      products could inhibit the migration of oral epithelial cells in an in vitro
      scratch assay. To compare, the oral bacteria Prevotella nigrescens, Prevotella
      intermedia, Tannerella forsythia, and Streptococcus mitis were included. A
      standardized scratch was made in a confluent layer of human oral epithelial
      cells. The epithelial cells were challenged with bacterial cells and with medium
      containing secretions of these bacteria. Closure of the scratch was measured
      after 17 h using a phase contrast microscope. P. gingivalis, P. nigrescens, and
      secretions of P. gingivalis strongly inhibited cell migration. A challenge with
      1000 heat-killed bacteria versus 1 epithelial cell resulted in a relative closure
      of the scratch of 25% for P. gingivalis and 20% for P. nigrescens. Weaker
      inhibitory effects were found for the other bacteria. The results confirmed our
      hypothesis that the oral bacteria may be involved in delayed wound healing. 

PMID- 24288440
TI  - Regulation of regenerative periodontal healing by NAMPT.
AB  - Periodontitis is an inflammatory disease characterized by destruction of the
      tooth-supporting tissues. Obese individuals have an increased risk of
      periodontitis, and elevated circulating levels of nicotinamide
      phosphoribosyltransferase (NAMPT) may be a pathomechanistic link between both
      diseases. Recently, increased levels of NAMPT have also been found in patients
      with periodontitis, irrespective of the presence of obesity. This in vitro study
      sought to examine the effects of NAMPT on the regenerative capacity of human
      periodontal ligament (PDL) cells and, thereby, periodontal healing. PDL cells
      treated with enamel matrix derivative (EMD), which was used to mimic regenerative
      healing conditions in vitro, were grown in the presence and absence of NAMPT for
      up to 14 d. EMD stimulated significantly (P < 0.05) the expression of growth
      factors and their receptors, matrix molecules, osteogenesis-associated factors,
      and wound closure and calcium accumulation. In the presence of NAMPT, all these
      stimulatory effects were significantly (P < 0.05) reduced. In conclusion, the
      beneficial effects of EMD on a number of PDL cell functions critical for
      periodontal regeneration are counteracted by NAMPT. Enhanced levels of NAMPT, as
      found in obesity and periodontal inflammation, may compromise the regenerative
      capacity of PDL cells and, thereby, periodontal healing in the presence of EMD. 

PMID- 24288441
TI  - Inflammation and pharmacological treatment in diabetic retinopathy.
AB  - Diabetic retinopathy (DR), the most common microvascular complication of diabetes
      mellitus, is estimated to be the leading cause of new blindness in the working
      population of developed countries. Primary interventions such as intensive
      glycemic control, strict blood pressure regulation, and lipid-modifying therapy
      as well as local ocular treatment (laser photocoagulation and pars plana
      vitrectomy) can significantly reduce the risk of retinopathy occurrence and
      progression. Considering the limitations of current DR treatments development of
      new therapeutic strategies, it becomes necessary to focus on pharmacological
      treatment. Currently, there is increasing evidence that inflammatory processes
      have a considerable role in the pathogenesis of DR with multiple studies showing
      an association of various systemic as well as local (vitreous and aqueous fluid)
      inflammatory factors and the progression of DR. Since inflammation is identified
      as a relevant mechanism, significant effort has been directed to the development
      of new concepts for the prevention and treatment of DR acting on the inflammatory
      processes and the use of pharmacological agents with anti-inflammatory effect.
      Inhibiting the inflammatory pathway could be an appealing treatment option for DR
      in future practices, and as further prospective randomized clinical trials
      accumulate data, the role and guidelines of anti-inflammatory pharmacologic
      treatments will become clearer. 

PMID- 24288442
TI  - Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte
      via promoting AMPK phosphorylation.
AB  - OBJECTIVE: Pigment epithelium-derived factor (PEDF) plays an important role in
      obesity-induced insulin resistance (IR). The study aims to investigate the effect
      of metformin, a widely used agent to improve IR, on PEDF production both in vivo
      and in vitro. METHODS: SD rats were divided into normal control group, high fat
      group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic
      clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and
      HepG2 cells were established and then treated with metformin and inhibitor of AMP
      activated protein kinase (AMPK). RESULTS: In vivo, the HF group showed increased
      serum PEDF which is negatively correlated with insulin sensitivity, while the MET
      group revealed decreased serum PEDF and downregulated PEDF expression in fat and
      liver, concomitant with significantly improved IR. In vitro, the IR cells showed
      enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion
      and expression, accompanied with increased glucose uptake. Metformin stimulated
      AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when
      combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated.
      CONCLUSIONS: Metformin inhibits the expression and secretion of PEDF in fat and
      liver via promoting AMPK phosphorylation, which is closely associated with IR
      improvement.

PMID- 24288444
TI  - Interleukin-16 polymorphism is associated with an increased risk of ischemic
      stroke.
AB  - Clinical and experimental data have demonstrated that inflammation plays
      fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16)
      is identified as a proinflammatory cytokine that is a key element in the ischemic
      cascade after cerebral ischemia. We aimed to examine the relationship between the
      IL-16 polymorphisms and the risk of ischemic stroke in a Chinese population. A
      total of 198 patients with ischemic stroke and 236 controls were genotyped using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      DNA sequencing method. We found that the rs11556218TG genotype and G allele of IL
      16 were associated with significantly increased risks of ischemic stroke (TG
      versus TT, adjusted OR = 1.88; 95% CI, 1.15-3.07; G versus T, adjusted OR = 1.54;
      95% CI, 1.05-2.27, resp.). However, there were no significant differences in the
      genotype and allele frequencies of IL-16 rs4778889 T/C and rs4072111 C/T
      polymorphisms between the two groups, even after stratification analyses by age,
      gender, and the presence or absence of hypertension, diabetes mellitus,
      hypercholesterolemia, and hypertriglyceridemia. These findings indicate that the
      IL-16 polymorphism may be related to the etiology of ischemic stroke in the
      Chinese population. 

PMID- 24288443
TI  - Alteration of energy substrates and ROS production in diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy is initiated by alterations in energy substrates. Despite
      excess of plasma glucose and lipids, the diabetic heart almost exclusively
      depends on fatty acid degradation. Glycolytic enzymes and transporters are
      impaired by fatty acid metabolism, leading to accumulation of glucose
      derivatives. However, fatty acid oxidation yields lower ATP production per mole
      of oxygen than glucose, causing mitochondrial uncoupling and decreased energy
      efficiency. In addition, the oxidation of fatty acids can saturate and cause
      their deposition in the cytosol, where they deviate to induce toxic metabolites
      or gene expression by nuclear-receptor interaction. Hyperglycemia, the fatty acid
      oxidation pathway, and the cytosolic storage of fatty acid and glucose/fatty acid
      derivatives are major inducers of reactive oxygen species. However, the presence
      of these species can be essential for physiological responses in the diabetic
      myocardium. 

PMID- 24288447
TI  - On Kolmogorov Asymptotics of Estimators of the Misclassification Error Rate in
      Linear Discriminant Analysis.
AB  - We provide a fundamental theorem that can be used in conjunction with Kolmogorov
      asymptotic conditions to derive the first moments of well-known estimators of the
      actual error rate in linear discriminant analysis of a multivariate Gaussian
      model under the assumption of a common known covariance matrix. The estimators
      studied in this paper are plug-in and smoothed resubstitution error estimators,
      both of which have not been studied before under Kolmogorov asymptotic
      conditions. As a result of this work, we present an optimal smoothing parameter
      that makes the smoothed resubstitution an unbiased estimator of the true error.
      For the sake of completeness, we further show how to utilize the presented
      fundamental theorem to achieve several previously reported results, namely the
      first moment of the resubstitution estimator and the actual error rate. We
      provide numerical examples to show the accuracy of the succeeding finite sample
      approximations in situations where the number of dimensions is comparable or even
      larger than the sample size.

PMID- 24288446
TI  - Inflammation and macular oedema after pars plana vitrectomy.
AB  - Cystoid macular oedema (CMO) is a major cause of reduced vision following
      intraocular surgery. Although the aetiology of CMO is not completely clarified,
      intraocular inflammation is known to play a major role in its development. The
      macula may develop cytotoxic oedema when the primary lesion and fluid
      accumulation occur in the parenchymatous cells (intracellular oedema) or
      vasogenic oedema when the primary defect occurs in the blood-retinal barrier and
      leads to extracellular fluid accumulation (extracellular oedema). We report on
      the mechanisms of CMO formation after pars plana vitrectomy and associated
      surgical procedures and discuss possible therapeutic approaches. 

PMID- 24288448
TI  - The role of beliefs in sexual behavior of adolescents: Development and validation
      of an Adolescent Sexual Expectancies Scale (ASEXS).
AB  - This paper reports on the development and psychometric properties of the
      Adolescent Sexual Expectancies Scale (ASEXS). Data were obtained from three
      annual longitudinal surveys of youth aged 10 - 17 at the first administration (N
      = 932 at Wave 3). Confirmatory factor analyses indicated that four correlated
      factors corresponding to Social Risk, Social Benefit, Health Risk, and Pleasure
      adequately represented the expectancy items. High alpha coefficients and
      stability across survey waves indicated good internal and test-retest reliability
      for these factors. Latent variable autoregressive analyses indicated that Social
      Risk expectancies predicted changes in sexual behavior over the course of the
      study. Multi-group analyses established that the measurement and predictive
      models were equivalent for males and females and across age groups. The ASEXS
      provides researchers with a useful measure for examining adolescents' expectancy
      beliefs about the consequences of sexual behavior.

PMID- 24288449
TI  - Aversive Peer Experiences on Social Networking Sites: Development of the Social
      Networking-Peer Experiences Questionnaire (SN-PEQ).
AB  - Cyber victimization is an important research area; yet, little is known about
      aversive peer experiences on social networking sites (SNSs), which are used
      extensively by youth and host complex social exchanges. Across samples of
      adolescents (n=216) and young adults (n=214), we developed the Social Networking
      Peer Experiences Questionnaire (SN-PEQ), and examined its psychometric
      properties, distinctiveness from traditional peer victimization, and associations
      with internalized distress. The SN-PEQ demonstrated strong factorial invariance
      and a single factor structure that was distinct from other forms of peer
      victimization. Negative SNS experiences were associated with youths' symptoms of
      social anxiety and depression, even when controlling for traditional peer
      victimization. Findings highlight the importance of examining the effects of
      aversive peer experiences that occur via social media.

PMID- 24288450
TI  - Measurement Properties of the Motivation for Youth Treatment Scale with a
      Residential Group Home Population.

PMID- 24288451
TI  - A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological
      Studies.
AB  - We present an innovative microfluidic approach to transcranial delivery of small
      quantities of drugs in brief time pulses for neurobiological studies. The
      approach is based on a two-stage process of consecutive drug dispensing and
      delivery, demonstrated by a device featuring a fully planar design in which the
      microfluidic components are integrated in a single layer. This 2-D configuration
      offers ease in device fabrication and is compatible to diverse actuation schemes.
      A compliance-based and normally closed check valve is used to couple the
      microchannels that are responsible for drug dispensing and delivery. Brief
      pneumatic pressure pulses are used to mobilize buffer and drug solutions, which
      are injected via a cannula into brain tissue. Thus, the device can potentially
      allow transcranial drug delivery and can also be potentially extended to enable
      transdermal drug delivery. We have characterized the device by measuring the
      dispensed and delivered volumes under varying pneumatic driving pressures and
      pulse durations, the standby diffusive leakage, and the repeatability in the
      delivery of multiple pulses of drug solutions. Results demonstrate that the
      device is capable of accurately dispensing and delivering drug solutions 5 to 70
      nL in volume within time pulses as brief as 50 ms, with negligible diffusive drug
      leakage over a practically relevant time scale. Furthermore, testing of pulsatile
      drug delivery into intact mouse brain tissue has been performed to demonstrate
      the potential application of the device to neurobiology.

PMID- 24288452
TI  - A Pilot Study Characterizing Real Time Exposures to Particulate Matter and Carbon
      Monoxide from Cookstove Related Woodsmoke in Rural Peru.
AB  - Nearly half of the world's population is exposed to household air pollution (HAP)
      due to long hours spent in close proximity to unvented cooking fires. We aimed to
      use PM2.5 and CO measurements to characterize exposure to cookstove generated
      woodsmoke in real time among control (n=10) and intervention (n=9) households in
      San Marcos, Cajamarca Region, Peru. Real time personal particulate matter with an
      aerodynamic diameter <=2.5 um (PM2.5), and personal and kitchen carbon monoxide
      (CO) samples were taken. Control households used a number of stoves including
      open fire and chimney stoves while intervention households used study-promoted
      chimney stoves. Measurements were categorized into lunch (9am - 1pm) and dinner
      (3pm - 7pm) periods, where applicable, to adjust for a wide range of sampling
      periods (2.8- 13.1hrs). During the 4-h time periods, mean personal PM2.5
      exposures were correlated with personal CO exposures during lunch (r=0.67 p=0.024
      n=11) and dinner (r=0.72 p=0.0011 n=17) in all study households. Personal PM2.5
      exposures and kitchen CO concentrations were also correlated during lunch (r=0.76
      p=0.018 n=9) and dinner (r=0.60 p=0.018 n=15). CO may be a useful indicator of PM
      during 4-h time scales measured in real time, particularly during high woodsmoke
      exposures, particularly during residential biomass cooking.

PMID- 24288453
TI  - Transformation of common wheat (Triticum aestivum L.) with avenin-like b gene
      improves flour mixing properties.
AB  - Avenin-like b proteins may contribute to the viscoelastic properties of wheat
      dough via inter-chain disulphide bonds, due to their rich cysteine residues. In
      order to clarify the effect of the avenin-like b proteins on the functional
      properties of wheat flour, the functional and biochemical properties of wheat
      flour were analyzed in three transgenic wheat lines overexpressing the avenin
      like b gene using the sodium dodecyl sulfate sedimentation (SDSS) test, Mixograph
      and size exclusion-high performance liquid chromatography (SE-HPLC) analysis. The
      results of the SDSS test and Mixograph analysis demonstrated that the
      overexpression of avenin-like b proteins in transgenic lines led to significantly
      increased SDSS volume and improved flour mixing properties. The results of SE
      HPLC analysis of the gluten proteins in wheat flour demonstrated that the
      improvement in transgenic line flour properties was associated with the increased
      proportion of large polymeric proteins due to the incorporation of overexpressed
      avenin-like b proteins into the glutenin polymers. These results could help to
      understand the influence and mechanism of avenin-like b proteins on the
      functional properties of wheat flour.

PMID- 24288454
TI  - Measuring social integration in a pilot randomized controlled trial of critical
      time: intervention-task shifting in Latin America.
AB  - Global mental health movements increasingly highlight the importance of social
      integration for individuals living with severe mental illnesses. However, this
      important individual-level outcome is rarely measured in programs. As part of
      RedeAmericas, a pilot regional randomized controlled trial of critical time
      intervention - task shifting - will be conducted, which includes social
      integration as an outcome measure. It is a time-limited care coordination model
      to enhance continuity of support for people with severe mental illness during
      critical periods of transition. Given the challenges of measuring social
      integration, particularly for a multi-country study with unique cultural
      contexts, this paper has described the measurement approach used to create a
      composite measure that uses items from disability and quality of life instruments
      in addition to other key items.

PMID- 24288455
TI  - The COPE Intervention for Caregivers of Patients with Heart Failure: An Adapted
      Intervention.

PMID- 24288456
TI  - Resource efficient hardware architecture for fast computation of running max/min
      filters.
AB  - Running max/min filters on rectangular kernels are widely used in many digital
      signal and image processing applications. Filtering with a k * k kernel requires
      of k(2) - 1 comparisons per sample for a direct implementation; thus, performance
      scales expensively with the kernel size k. Faster computations can be achieved by
      kernel decomposition and using constant time one-dimensional algorithms on custom
      hardware. This paper presents a hardware architecture for real-time computation
      of running max/min filters based on the van Herk/Gil-Werman (HGW) algorithm. The
      proposed architecture design uses less computation and memory resources than
      previously reported architectures when targeted to Field Programmable Gate Array
      (FPGA) devices. Implementation results show that the architecture is able to
      compute max/min filters, on 1024 * 1024 images with up to 255 * 255 kernels, in
      around 8.4 milliseconds, 120 frames per second, at a clock frequency of 250 MHz.
      The implementation is highly scalable for the kernel size with good
      performance/area tradeoff suitable for embedded applications. The applicability
      of the architecture is shown for local adaptive image thresholding.

PMID- 24288457
TI  - A new and environmentally friendly route for preparation of carbon microspheres
      from wheat straw.
AB  - The reactions were performed to synthesize carbon materials using wheat straw
      powder as raw material. The wheat straw powder was first hydrolyzed at the
      absence of a catalyst at 190  degrees C for 1 h, then the hydrolyzate solution
      was used as carbon source to prepare carbon materials via hydrothermal
      carbonization at 180  degrees C in the absence of a catalyst for 8 h. The
      influence of solid-liquid-ratio of wheat straw to water on the morphology of the
      product was investigated. The samples were examined by a scanning electron
      microscope and Fourier transform infrared spectroscopy. The results show that the
      product was carbon microspheres with a large number of O-H, CHO, and other
      functional groups, and the diameters of carbon microspheres noticeably depended
      on the solid-liquid ratio. When the solid-liquid ratio was 1 : 60, the diameters
      of carbon microspheres were in the range of 100 to 300 nm when the solid-liquid
      ratio was 1 : 40, carbon microspheres with larger and more uniform diameters
      mostly about 250 nm were obtained, and when the solid-liquid-ratio was 1 : 20,
      there were more larger carbon microspheres with diameters about 800 nm in the
      product and the surface of these carbon microspheres is smoother, whereas; the
      uniformity of the product deteriorates.

PMID- 24288458
TI  - On harmonic meromorphic functions associated with basic hypergeometric functions.
AB  - By making use of basic hypergeometric functions, a class of complex harmonic
      meromorphic functions with positive coefficients is introduced. We obtain some
      properties such as coefficient inequality, growth theorems, and extreme points. 

PMID- 24288459
TI  - Perinatal palliative care: barriers and attitudes of neonatologists and nurses in
      Poland.
AB  - OBJECTIVE: To identify barriers and personnel attitudes towards realization of
      palliative care principles in neonatological units. STUDY DESIGN: An anonymous
      questionnaire was posted to all heads of departments and head nurses of all the
      27 neonatological units in the Lodz area. RESULTS: We received 46 (85%)
      questionnaires. Final analysis comprised 42 properly filled-in questionnaires (by
      22 doctors and 20 nurses). In case of prenatal diagnosis of a lethal defect,
      77.27% of doctors and 65% of nurses opted for informing the mother also about the
      possibility of pregnancy continuation and organization of palliative care after
      delivery. Most of respondents accepted conditions for abortion pointed by the
      Polish law. The most common barriers pointed out by both groups were insufficient
      knowledge of the personnel on palliative medicine and family preference for life
      sustaining treatment. CONCLUSIONS: Understanding attitudes of personnel towards
      palliative care and identification of barriers are a starting point for future
      efforts to improve the system of neonatological care.

PMID- 24288460
TI  - Advancement perforator cheek flap for aesthetic one-stage reconstruction of
      postoncological extended split-thickness defects of the nasal sidewall.
AB  - Aesthetic reconstruction of soft tissue nasal sidewall loss has an important
      influence on the appearance of the nose. The unique character of this subunit and
      the complex relationships with a number of different facial or nasal subunits
      make the excision of large tumors difficult to manage. Numerous techniques are
      described in the literature, but a primary reconstruction with a final good
      result is not often possible. The authors develop an advancement cheek flap for
      an aesthetic one-stage reconstruction of postoncological extended nasal sidewall
      defects. Between January 2009 and July 2012, 16 patients (mean age, 63.3 yr)
      underwent excision of skin tumors of nasal sidewall and immediate reconstruction
      with an advancement cheek flap nourished by perforators from the transverse
      facial branch of the superficial temporal artery. The tumors were excised with
      0.4-0.6 cm lateral margins and defects size ranged from 2.6 * 2.6 cm to 3.5 * 5
      cm. Oncological radicality was obtained in all cases. The aesthetic results were
      excellent in all patients. No scar revision was needed. The authors' advancement
      cheek flap can be considered the first choice for reconstruction of split
      thickness defect of nasal sidewall larger than 2.5 cm because it reestablishes in
      one stage the nasal contour detail.

PMID- 24288461
TI  - Phase transition in long-range percolation on bipartite hierarchical lattices.
AB  - We propose a family of bipartite hierarchical lattice of order N governed by a
      pair of parameters l and gamma. We study long-range percolation on the bipartite
      hierarchical lattice where any edge (running between vertices of unlike
      bipartition sets) of length k is present with probability p k = 1 - exp(
      alphabeta (-k)), independently of all other edges. The parameter alpha is the
      percolation parameter, while beta describes the long-range nature of the model.
      The model exhibits a nontrivial phase transition in the sense that a critical
      value alpha c [Symbol: see text] (0, infinity) if and only if l >= 1, 1 <= gamma
      <= N - 1, and beta [Symbol: see text] (N, N (2)). Moreover, the infinite
      component is unique when alpha > alpha c .

PMID- 24288462
TI  - The paradox role of regulatory T cells in ischemic stroke.
AB  - The underlying mechanism of ischemic stroke is not completely known. Regulatory T
      cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological
      process of ischemic stroke. However, there is also controversy over the role of
      Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a
      heated discussion recently. In this paper, we reviewed the current lines of
      evidence to describe the full view of Tregs in stroke. We would like to introduce
      the basic concepts of Tregs and then discuss their paradox function in ischemic
      stroke. On one side, Tregs could protect brain against ischemic injury via
      modulating the inflammation process. On the other side, they exaggerated the
      insult by causing microvascular dysfunction. They also interfered with the
      neurological function recovery. In addition, the reasons for this paradox role
      would be discussed in the review and the prospective of the clinical application
      of Tregs was also included. In conclusion, Tregs contributed to the outcome of
      ischemic stroke, while more lines of evidence are needed to understand how Tregs
      regulate the immune system and influence the outcome of stroke. 

PMID- 24288463
TI  - Mitochondrial quality control: decommissioning power plants in neurodegenerative
      diseases.
AB  - The cell has an intricate quality control system to protect its mitochondria from
      oxidative stress. This surveillance system is multi-tiered and comprises
      molecules that are present inside the mitochondria, in the cytosol, and in other
      organelles like the nucleus and endoplasmic reticulum. These molecules cross talk
      with each other and protect the mitochondria from oxidative stress. Oxidative
      stress is a fundamental part of early disease pathogenesis of neurodegenerative
      diseases. These disorders also damage the cellular quality control machinery that
      protects the cell against oxidative stress. This exacerbates the oxidative damage
      and causes extensive neuronal cell death that is characteristic of
      neurodegeneration. 

PMID- 24288464
TI  - Comparison analysis of coal biodesulfurization and coal's pyrite bioleaching with
      Acidithiobacillus ferrooxidans.
AB  - Acidithiobacillus ferrooxidans (A. ferrooxidans) was applied in coal
      biodesulfurization and coal's pyrite bioleaching. The result showed that A.
      ferrooxidans had significantly promoted the biodesulfurization of coal and
      bioleaching of coal's pyrite. After 16 days of processing, the total sulfur
      removal rate of coal was 50.6%, and among them the removal of pyritic sulfur was
      up to 69.9%. On the contrary, after 12 days of processing, the coal's pyrite
      bioleaching rate was 72.0%. SEM micrographs showed that the major pyrite forms in
      coal were massive and veinlets. It seems that the bacteria took priority to
      remove the massive pyrite. The sulfur relative contents analysis from XANES
      showed that the elemental sulfur (28.32%) and jarosite (18.99%) were accumulated
      in the biotreated residual coal. However, XRD and XANES spectra of residual
      pyrite indicated that the sulfur components were mainly composed of pyrite
      (49.34%) and elemental sulfur (50.72%) but no other sulfur contents were
      detected. Based on the present results, we speculated that the pyrite forms in
      coal might affect sulfur biooxidation process. 

PMID- 24288465
TI  - Behaviour of plate anchorage in plate-reinforced composite coupling beams.
AB  - As a new alternative design, plate-reinforced composite (PRC) coupling beam
      achieves enhanced strength and ductility by embedding a vertical steel plate into
      a conventionally reinforced concrete (RC) coupling beam. Based on a nonlinear
      finite element model developed in the authors' previous study, a parametric study
      presented in this paper has been carried out to investigate the influence of
      several key parameters on the overall performance of PRC coupling beams. The
      effects of steel plate geometry, span-to-depth ratio of beams, and steel
      reinforcement ratios at beam spans and in wall regions are quantified. It is
      found that the anchorage length of the steel plate is primarily controlled by the
      span-to-depth ratio of the beam. Based on the numerical results, a design curve
      is proposed for determining the anchorage length of the steel plate. The load
      carrying capacity of short PRC coupling beams with high steel ratio is found to
      be controlled by the steel ratio of wall piers. The maximum shear stress of PRC
      coupling beams should be limited to 15 MPa.

PMID- 24288466
TI  - Comparison of VIDAS and radioimmunoassay methods for measurement of cortisol
      concentration in bovine serum.
AB  - Radioimmunoassay (RIA) is the "gold standard" method for evaluation of serum
      cortisol concentration. The VIDAS cortisol test is an enzyme-linked fluorescent
      assay designed for the MiniVidas system. The aim of this study was to compare the
      VIDAS method with RIA for measurement of bovine serum cortisol concentration.
      Cortisol concentrations were evaluated in 40 cows using both VIDAS and RIA
      methods, the latter as the reference method. A paired Student's t-test, Pearson's
      correlation analysis, Bland-Altman plot, and Deming regression analysis were used
      to compare the two methods. There was no statistically significant difference
      between mean serum cortisol concentrations measured by VIDAS or RIA methods (P =
      0.6570). Both methods were able to detect significant differences in mean low and
      high cortisol concentrations (P < 0.00014 RIA and P < 0.0016 VIDAS). The
      correlation coefficient was low, but a Bland-Altman plot and Deming regression
      analysis show neither constant nor proportional error. The VIDAS method produced
      slightly higher values than RIA, but the difference was small and in no case did
      the mean value move the normal range. Results suggest that VIDAS method is
      suitable for the determination of bovine serum cortisol concentration in studies
      of large numbers of animals. 

PMID- 24288467
TI  - Identification of urban leprosy clusters.
AB  - Overpopulation of urban areas results from constant migrations that cause
      disordered urban growth, constituting clusters defined as sets of people or
      activities concentrated in relatively small physical spaces that often involve
      precarious conditions. Aim. Using residential grouping, the aim was to identify
      possible clusters of individuals in Sao Jose do Rio Preto, Sao Paulo, Brazil, who
      have or have had leprosy. Methods. A population-based, descriptive, ecological
      study using the MapInfo and CrimeStat techniques, geoprocessing, and space-time
      analysis evaluated the location of 425 people treated for leprosy between 1998
      and 2010. Clusters were defined as concentrations of at least 8 people with
      leprosy; a distance of up to 300 meters between residences was adopted.
      Additionally, the year of starting treatment and the clinical forms of the
      disease were analyzed. Results. Ninety-eight (23.1%) of 425 geocoded cases were
      located within one of ten clusters identified in this study, and 129 cases
      (30.3%) were in the region of a second-order cluster, an area considered of high
      risk for the disease. Conclusion. This study identified ten clusters of leprosy
      cases in the city and identified an area of high risk for the appearance of new
      cases of the disease. 

PMID- 24288469
TI  - Histology and ultrastructure of transitional changes in skin morphology in the
      juvenile and adult four-striped mouse (Rhabdomys pumilio).
AB  - The four-striped mouse has a grey to brown coloured coat with four characteristic
      dark stripes interspersed with three lighter stripes running along its back. The
      histological differences in the skin of the juvenile and adult mouse were
      investigated by Haematoxylin and Eosin and Masson Trichrome staining, while
      melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide
      staining. The ultrastructure of the juvenile skin, hair follicles, and
      melanocytes was also explored. In both the juvenile and adult four-striped mouse,
      pigment-containing cells were observed in the dermis and were homogeneously
      dispersed throughout this layer. Apart from these cells, the histology of the
      skin of the adult four-striped mouse was similar to normal mammalian skin. In the
      juvenile four-striped mouse, abundant hair follicles of varying sizes were
      observed in the dermis and hypodermis, while hair follicles of similar size were
      only present in the dermis of adult four-striped mouse. Ultrastructural analysis
      of juvenile hair follicles revealed that the arrangement and differentiation of
      cellular layers were typical of a mammal. This study therefore provides unique
      transition pattern in the four-striped mouse skin morphology different from the
      textbook description of the normal mammalian skin. 

PMID- 24288468
TI  - Targeting apoptosis pathways in cancer with alantolactone and isoalantolactone.
AB  - Alantolactone and isoalantolactone, main bioactive compounds that are present in
      many medicinal plants such as Inula helenium, L. Inula japonica, Aucklandia
      lappa, Inula racemosa, and Radix inulae, have been found to have various
      pharmacological actions including anti-inflammatory, antimicrobial, and
      anticancer properties, with no significant toxicity. Recently, the anticancer
      activity of alantolactone and isoalantolactone has been extensively investigated.
      Here, our aim is to review their natural sources and their anticancer activity
      with specific emphasis on mechanism of actions, by which these compounds act on
      apoptosis pathways. Based on the literature and also on our previous results,
      alantolactone and isoalantolactone induce apoptosis by targeting multiple
      cellular signaling pathways that are frequently deregulated in cancers and
      suggest that their simultaneous targeting by these compounds could result in
      efficacious and selective killing of cancer cells. This review suggests that
      alantolactone and isoalantolactone are potential promising anticancer candidates,
      but additional studies and clinical trials are required to determine their
      specific intracellular sites of actions and derivative targets in order to fully
      understand the mechanisms of therapeutic effects to further validate in cancer
      chemotherapy. 

PMID- 24288470
TI  - Intranuclear crosstalk between extracellular regulated kinase1/2 and signal
      transducer and activator of transcription 3 regulates JEG-3 choriocarcinoma cell
      invasion and proliferation.
AB  - Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via
      leukemia inhibitory factor- (LIF-) induced activation of signal transducer and
      activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at
      its ser727 binding site, possible crosstalk with intracellular MAPK signaling,
      and their functional implications are the object of the present investigation.
      JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the
      specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p
      STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per
      Western blot. Immunocytochemistry confirmed results, but also pinpointed the
      location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was
      studied with a colorimetric ELISA-based assay. Cell viability and invasion
      capability were assessed by MTS and Matrigel assays. Our results demonstrate that
      LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly
      increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness
      are enhanced after LIF stimulation and ERK1/2 blockage. In contrast,
      proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The
      findings herein show that blocking ERK1/2 increases LIF-induced STAT3
      phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk,
      which leads to enhanced invasiveness and reduced proliferation. 

PMID- 24288471
TI  - Renin and the IGFII/M6P receptor system in cardiac biology.
AB  - Nonenzymatic cardiac activities of renin are well described during the last years
      and contribute either to cardiac-specific effects of the renin-angiotensin
      aldosterone-system (RAAS) or to the pharmacological effects of RAAS inhibition.
      The interaction of renin with insulin-like growth factor II/mannose-6-phosphate
      (IGFII/M6P) receptors participates in nonclassical renin effects and contributes
      to cardiac remodelling caused by RAAS activation. The current findings suggest an
      important role for renin IGFII/M6P receptor interaction in cardiac adaptation to
      stress and support the idea that excessive accumulation of renin during
      inhibition of RAAS directly contributes to blood pressure-independent effects of
      these pharmacological interventions. It becomes a challenge for future studies
      focussing on chronic hypertension or myocardial infarction to comprise regulatory
      adaptations of the kidney, the main source of plasma renin and prorenin, because
      they directly contribute to key steps in regulation of cardiac (mal)adaptation
      via IGFII/M6P receptors. This receptor system is part of peptide/receptor
      interactions that modifies and possibly limits adverse remodelling effects caused
      by angiotensin II. Evaluation of interactions of renin with other pro
      hypertrophic agonists is required to decide whether this receptor may become a
      target of pharmacological intervention. 

PMID- 24288472
TI  - Intelligence deficits in Chinese patients with brain tumor: the impact of tumor
      resection.
AB  - BACKGROUND: Intelligence is much important for brain tumor patients after their
      operation, while the reports about surgical related intelligence deficits are not
      frequent. It is not only theoretically important but also meaningful for clinical
      practice. METHODS: Wechsler Adult Intelligence Scale was employed to evaluate the
      intelligence of 103 patients with intracranial tumor and to compare the
      intelligence quotient (IQ), verbal IQ (VIQ), and performance IQ (PIQ) between the
      intracerebral and extracerebral subgroups. RESULTS: Although preoperative
      intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found
      to have any significant difference between the intracerebral and extracerebral
      subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate
      postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral
      subgroup, but an improvement of VIQ in the right intracerebral subgroup.
      Pituitary adenoma resection exerted no effect on intelligence. In addition, age,
      years of education, and tumor size were found to play important roles.
      CONCLUSIONS: Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor
      resection can deteriorate IQ and PIQ. However, right intracerebral tumor
      resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection
      performs no effect on intelligence.

PMID- 24288473
TI  - Application of potential phosphate-solubilizing bacteria and organic acids on
      phosphate solubilization from phosphate rock in aerobic rice.
AB  - A study was conducted at Universiti Putra Malaysia to determine the effect of
      phosphate-solubilizing bacteria (PSB) and organic acids (oxalic & malic) on
      phosphate (P) solubilization from phosphate rock (PR) and growth of aerobic rice.
      Four rates of each organic acid (0, 10, 20, and 30 mM), and PSB strain (Bacillus
      sp.) were applied to aerobic rice. Total bacterial populations, amount of P
      solubilization, P uptake, soil pH, and root morphology were determined. The
      results of the study showed significantly high P solubilization in PSB with
      organic acid treatments. Among the two organic acids, oxalic acid was found more
      effective compared to malic acid. Application of oxalic acid at 20 mM along with
      PSB16 significantly increased soluble soil P (28.39 mg kg(-1)), plant P uptake
      (0.78 P pot(-1)), and plant biomass (33.26 mg). Addition of organic acids with
      PSB and PR had no influence on soil pH during the planting period. A higher
      bacterial population was found in rhizosphere (8.78 log10 cfu g(-1)) compared to
      the nonrhizosphere and endosphere regions. The application of organic acids along
      with PSB enhanced soluble P in the soil solution, improved root growth, and
      increased plant biomass of aerobic rice seedlings without affecting soil pH.

PMID- 24288474
TI  - Structural properties of liquid SiC during rapid solidification.
AB  - The rapid solidification of liquid silicon carbide (SiC) is studied by molecular
      dynamic simulation using the Tersoff potential. The structural properties of
      liquid and amorphous SiC are analyzed by the radial distribution function,
      angular distribution function, coordination number, and visualization technology.
      Results show that both heteronuclear and homonuclear bonds exist and no atomic
      segregation occurs during solidification. The bond angles of silicon and carbon
      atoms are distributed at around 109 degrees  and 120 degrees , respectively, and
      the average coordination number is <4. Threefold carbon atoms and fourfold
      silicon atoms are linked together by six typical structures and ultimately form a
      random network of amorphous structure. The simulated results help understand the
      structural properties of liquid and amorphous SiC, as well as other similar
      semiconductor alloys. 

PMID- 24288475
TI  - Synthesis and biological evaluation of 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl
      4-[(alkoxycarbonyl)amino]benzoates.
AB  - A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4
      [(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar
      compounds have been described as potential antimycobacterials, primary in vitro
      screening of the synthesized carbamates was also performed against two
      mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4
      (butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4
      methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride,
      and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4
      (butoxycarbonylamino)benzoate hydrochloride showed higher activity against M.
      avium subsp. paratuberculosis and M. intracellulare than the standards
      ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective
      compounds was performed using the human monocytic leukaemia THP-1 cell line.
      Compounds with predicted amphiphilic properties were also tested for their
      effects on the rate of photosynthetic electron transport (PET) in spinach
      (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly
      stimulated the rate of PET, indicating that the compounds can induce
      conformational changes in thylakoid membranes resulting in an increase of their
      permeability and so causing uncoupling of phosphorylation from electron
      transport. 

PMID- 24288476
TI  - On the differential diagnosis of anxious from nonanxious major depression by
      means of the Hamilton Scales.
AB  - OBJECTIVE: Anxious major depressive disorder (A-MDD) is differentially diagnosed
      from nonanxious MDD (NA-MDD) as MDD with a cut-off score >= 7 on the HAM-D
      anxiety-somatization factor (ASF). We investigated whether additional HAM-D items
      discriminate A-MDD from NA-MDD. Moreover, we tested the validity of ASF criterion
      against HAM-A, gold standard of anxiety severity assessment. METHODS: 164
      consecutive female middle-aged inpatients, diagnosed as A-MDD (n = 92) or NA-MDD
      (n = 72) by the normative HAM-A score for moderate-to-severe anxiety (>= 25),
      were compared regarding 17-item HAM-D scores. The validity of ASF >= 7 criterion
      was assessed by receiver-operating characteristics (ROC) analysis. RESULTS: We
      found medium and large effect size differences between A-MDD and NA-MDD patients
      in only four out of the six ASF items, as well as in three further HAM-D items,
      namely, those of agitation, middle insomnia, and delayed insomnia. Furthermore,
      the ASF cut-off score >= 9 provided the optimal trade-off between sensitivity and
      specificity for the differential diagnosis between A-MDD and NA-MDD. CONCLUSION:
      Additional HAM-D items, beyond those of ASF, discriminate A-MDD from NA-MDD. The
      ASF >= 7 criterion inflates false positives. A cut-off point >= 9 provides the
      best trade-off between sensitivity and specificity of the ASF criterion, at least
      in female middle-aged inpatients.

PMID- 24288477
TI  - A retrospective chart review of treatment seeking middle aged individuals at a
      tertiary care substance use disorder treatment centre in North Part of India over
      five successive years: findings from drug abuse monitoring system.
AB  - Adolescents and young adults continue to remain the main focus of attention with
      regards to substance use related problems. There has been a limited focus on
      illicit substance use among middle aged and elderly population. The current study
      explored the changing trends of substance use among treatment seeking middle aged
      individuals (aged 40-60 years) at a tertiary level drug dependence treatment
      centre. The questionnaire used to gather information for the study is a 19-item
      structured questionnaire. It includes information on various sociodemographic
      variables, "current," and "ever" use of substance. Information is also collected
      on variables related to high risk injecting drug use and HIV status of the
      individuals. There has been consistent increase in the population of treatment
      seekers over five years. Over the five-year period, the absolute percentage
      increase in treatment seeking population is approximately 21%. Polysubstance use
      was found to increase significantly over five-study years (P(Trend) = 0.007).

PMID- 24288478
TI  - Optical properties of polypropylene upon recycling.
AB  - In the last few years there has been an increasing interest in the possibility of
      recycling polymeric materials, using physical recycling. However, is it well
      known that polymers experience a depletion of all the properties upon recycling.
      These effects have been widely characterized in the literature for what concerns
      the mechanical or rheological properties. The changes of optical properties after
      recycling have been much less studied, even if, especially in food packaging,
      optical characteristics (above all the opacity) are of extreme importance, and
      thus it is quite significant to assess the effect of recycling on these
      properties. In this work, the influence of recycling steps on the opacity of
      films of a commercial grade of isotactic polypropylene (i-PP) was studied. The
      material was extruded several times to mimic the effect of recycling procedures.
      After extrusion, films were obtained by cooling samples of material at different
      cooling rates. The opacity of the obtained films was then measured and related to
      their crystallinity and morphology. It was found that opacity generally increases
      on increasing the amount of alpha phase and for the same amount of alpha phase on
      increasing the size of the spherulites. 

PMID- 24288479
TI  - Transport model of underground sediment in soils.
AB  - Studies about sediment erosion were mainly concentrated on the river channel
      sediment, the terrestrial sediment, and the underground sediment. The transport
      process of underground sediment is studied in the paper. The concept of the flush
      potential sediment is founded. The transport equation with stable saturated
      seepage is set up, and the relations between the flush potential sediment and
      water sediment are discussed. Flushing of underground sediment begins with small
      particles, and large particles will be taken away later. The pore ratio of the
      soil increases gradually. The flow ultimately becomes direct water seepage, and
      the sediment concentration at the same position in the water decreases over time.
      The concentration of maximal flushing potential sediment decreases along the
      path. The underground sediment flushing model reflects the flushing mechanism of
      underground sediment. 

PMID- 24288480
TI  - Generation of mature Nalpha-terminal acetylated thymosin alpha 1 by cleavage of
      recombinant prothymosin alpha.
AB  - N(alpha)-terminal acetylation of peptides plays an important biological role but
      is rarely observed in prokaryotes. N(alpha)-terminal acetylated thymosin alpha1
      (Talpha1), a 28-amino-acid peptide, is an immune modifier that has been used in
      the clinic to treat hepatitis B and C virus (HBV/HCV) infections. We previously
      documented N(alpha)-terminal acetylation of recombinant prothymosin alpha
      (ProTalpha) in E. coli. Here we present a method for production of N(alpha)
      acetylated Talpha1 from recombinant ProTalpha. The recombinant ProTalpha was
      cleaved by human legumain expressed in Pichia pastoris to release Talpha1 in
      vitro. The N(alpha)-acetylated Talpha1 peptide was subsequently purified by
      reverse phase and cation exchange chromatography. Mass spectrometry indicated
      that the molecular mass of recombinant N(alpha)-acetylated Talpha1 was 3108.79
      in, which is identical to the mass of N(alpha)-acetylated Talpha1 produced by
      total chemical synthesis. This mass corresponded to the nonacetylated Talpha1
      mass with a 42 Da increment. The retention time of recombinant N(alpha)
      acetylated Talpha1 and chemosynthetic N(alpha)-acetylated Talpha1 were both 15.4
      min in RP-high performance liquid chromatography (HPLC). These data support the
      use of an E. coli expression system for the production of recombinant human
      N(alpha)-acetylated Talpha1 and also will provide the basis for the preparation
      of recombinant acetylated peptides in E. coli.

PMID- 24288481
TI  - Pathology survey on a captive-bred colony of the Mexican Goodeid, nearly extinct
      in the wild, Zoogoneticus tequila (Webb & Miller 1998).
AB  - The Mexican Goodeid, Zoogoneticus tequila, is considered nearly extinct in the
      wild and it is maintained in captivity by the nonprofit international "Goodeid
      Working Group." The unique Italian colony has produced about 180 fish so far. The
      observable diseases were registered and some fish were submitted, immediately
      after spontaneous death, to necroscopic and histopathologic exams. Encountered
      diseases included the following: 7 cases of scoliosis (2 males and 5 females); 2
      fish with a similar congenital deviation of ocular axis; 1 adult male with left
      corneal opacity, presumably of traumatic origin; 1 female fish with a large
      subocular fluid-filled sac, histologically referable to a lymphatic cyst,
      similarly to the eye sacs of a Goldfish variety (Carassius auratus) called bubble
      eye; and 1 female fish with recurrent abdominal distension consequent to distal
      bowel dilation and thinning, associated with complete mucosal atrophy, and
      comparable to intestinal pseudo-obstruction syndromes described in humans and
      various animal species. The absence of infectious or parasitic diseases, as well
      as the low incidence of diseases potentially related to environmental alterations
      or nutritional disorders such as spinal deformities, suggests the adequacy of
      breeding management techniques of Z. tequila for its conservation and
      reintroduction in to the original habitat in the near future. 

PMID- 24288482
TI  - Correlates of and barriers to the utilization of health services for delivery in
      South Asia and Sub-Saharan Africa.
AB  - The high maternal and neonatal mortality rates in South Asia and Sub-Saharan
      Africa can be attributed to the lack of access and utilization of health services
      for delivery. Data from the Demographic and Health Surveys conducted in
      Bangladesh, India, Pakistan, Kenya, Nigeria, and Tanzania show that more than
      half of the births in these countries were delivered outside a health facility.
      Institutional delivery was closely associated with educational level, family
      wealth, place of residence, and women's media exposure status, but it was not
      influenced by women's work status and their roles in decision-making (with the
      exception of Nigeria). Controlling for other variables, higher parity and younger
      women were less likely to use a health facility for delivery. Within each
      country, the poorer, less educated and rural women had higher unmet need for
      maternal care services. Service related factors (accessibility in terms of cost
      and distance) and sociocultural factors (e.g., did not perceive the need for the
      services and objections from husband and family) also posed as barriers to
      institutional delivery. The paper concludes with some suggestions to increase
      institutional delivery. 

PMID- 24288483
TI  - Unsupervised performance evaluation strategy for bridge superstructure based on
      fuzzy clustering and field data.
AB  - Performance evaluation of a bridge is critical for determining the optimal
      maintenance strategy. An unsupervised bridge superstructure state assessment
      method is proposed in this paper based on fuzzy clustering and bridge field
      measured data. Firstly, the evaluation index system of bridge is constructed.
      Secondly, a certain number of bridge health monitoring data are selected as
      clustering samples to obtain the fuzzy similarity matrix and fuzzy equivalent
      matrix. Finally, different thresholds are selected to form dynamic clustering
      maps and determine the best classification based on statistic analysis. The
      clustering result is regarded as a sample base, and the bridge state can be
      evaluated by calculating the fuzzy nearness between the unknown bridge state data
      and the sample base. Nanping Bridge in Jilin Province is selected as the
      engineering project to verify the effectiveness of the proposed method. 

PMID- 24288484
TI  - A ternary catalytic system for the room temperature Suzuki-Miyaura reaction in
      water.
AB  - The formation of Pd(0) in the absence of any classical reducing agent in a medium
      containing Mg(2+)/Al(3+) layered double hydroxide (LDH) and N,N-dimethylformamide
      was evidenced. XRD analysis showed the presence of crystalline phases of
      palladium in the Pd/LDH composite. Suzuki-Miyaura reactions in aqueous medium
      were carried out at room temperature, and good yields were obtained with
      bromoarenes and iodoarenes using the ternary system LDH-Pd-CD (cyclodextrin) as
      catalyst. 

PMID- 24288485
TI  - Enhancing the dyeability of polypropylene fibers by melt blending with
      polyethylene terephthalate.
AB  - Attempts were made to modify polypropylene fibers by melt blending with
      polyethylene terephthalate in order to enhance the dyeability of the resultant
      fiber. Five blends of polypropylene/polyethylene terephthalate/compatibilizer
      were prepared and subsequently spun into fibers. Three disperse dyes were used to
      dye such modified fibers at boiling and 130  degrees C. The dyeing performance of
      the blend fibers, as well as the morphological, chemical, thermal, and mechanical
      properties, of the corresponding blends was characterized by means of
      spectrophotometry, polarized optical microscopy, scanning electron microscopy
      (SEM), FT-IR spectroscopy, differential scanning calorimetry (DSC), and tensile
      testing.

PMID- 24288486
TI  - Multiple myeloma and kidney disease.
AB  - Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to
      treatments differs considerably among patients because of high heterogeneity of
      MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and
      treatment-related mortality and morbidity are higher in MM patients with CKD than
      in patients with normal renal function. Recent advances in diagnostic tests,
      chemotherapy agents, and dialysis techniques are providing clinicians with novel
      approaches for the management of MM patients with CKD. Once reversible factors,
      such as hypercalcemia, have been corrected, the most common cause of severe acute
      kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which
      results from very high circulating concentrations of monoclonal immunoglobulin
      free light chains (FLC). In the setting of AKI, an early reduction of serum FLC
      concentration is related to kidney function recovery. The combination of extended
      high cutoff hemodialysis and chemotherapy results in sustained reductions in
      serum FLC concentration in the majority of patients and a high rate of
      independence from dialysis. 

PMID- 24288487
TI  - Influence of febrile neutropenia period on plasma viscosity at malignancy.
AB  - Cancer, chemotherapy, and infections all together make changes in blood rheology
      and may affect the defense mechanisms by changing the thrombocyte function and
      endothelial cell. We have examined changes of blood rheology on plasma viscosity
      to put on probable following criteria for starting the treatment of febrile
      neutropenia immediately. A total of 27 postchemotherapy patients (16 males and 11
      females) with febrile neutropenia diagnosed according to international guidelines
      have been included into the study. The plasma viscosity of the patients whose
      febrile neutropenia has been successfully treated was also measured to assess the
      impact of the duration of neutropenia on viscosity. The plasma viscosities of the
      patients were significantly higher during neutropenic episode than in
      nonneutropenic state (P = 0.006) except for alkaline phosphatase. All study
      parameters, particularly acute phase reactants, were statistically similar during
      both states. In the correlation of analysis with study parameters and stages,
      significant correlation was not observed between plasma viscosity alteration and
      leukocyte-neutrophil alteration, also other study parameters. We have
      demonstrated significantly elevated plasma viscosity in our patients during
      febrile neutropenic episode. Despite normal values of various parameters known to
      trigger plasma viscosity, particularly fibrinogen, it can be easily argued that
      the main mechanism may be the endothelial injury during infectious process and
      immune response mediated microcirculatory blood flow alterations. 

PMID- 24288488
TI  - Immigrant health inequalities in the United States: use of eight major national
      data systems.
AB  - Eight major federal data systems, including the National Vital Statistics System
      (NVSS), National Health Interview Survey (NHIS), National Survey of Children's
      Health, National Longitudinal Mortality Study, and American Community Survey,
      were used to examine health differentials between immigrants and the US-born
      across the life course. Survival and logistic regression, prevalence, and age
      adjusted death rates were used to examine differentials. Although these data
      systems vary considerably in their coverage of health and behavioral
      characteristics, ethnic-immigrant groups, and time periods, they all serve as
      important research databases for understanding the health of US immigrants. The
      NVSS and NHIS, the two most important data systems, include a wide range of
      health variables and many racial/ethnic and immigrant groups. Immigrants live 3.4
      years longer than the US-born, with a life expectancy ranging from 83.0 years for
      Asian/Pacific Islander immigrants to 69.2 years for US-born blacks. Overall,
      immigrants have better infant, child, and adult health and lower disability and
      mortality rates than the US-born, with immigrant health patterns varying across
      racial/ethnic groups. Immigrant children and adults, however, fare substantially
      worse than the US-born in health insurance coverage and access to preventive
      health services. Suggestions and new directions are offered for improvements in
      health monitoring and for strengthening and developing databases for immigrant
      health assessment in the USA. 

PMID- 24288489
TI  - A higher tidal volume may be used for athletes according to measured FVC.
AB  - We investigated whether professional athletes may require higher tidal volume (Tv
      ) during mechanical ventilation hypothesizing that they have significantly higher
      "normal" lung volumes compared to what was predicted and to nonathletes. Measured
      and predicted spirometric values were recorded in both athletes and nonathletes
      using a Spirovit SP-1 spirometer (Schiller, Switzerland). Normal Tv (6 mL/kg of
      predicted body weight) was calculated as a percentage of measured and predicted
      forced vital capacity (FVC) and the difference (delta) was used to calculate the
      additional Tv required using the equation: New Tv(TvN) = Tv + (Tv * delta).
      Professional athletes had significantly higher FVC compared to what was predicted
      (by 9% in females and 10% in males) and to nonathletes. They may also require a
      Tv of 6.6 mL/kg for males and 6.5 mL/kg for females during mechanical
      ventilation. Nonathletes may require a T v of 5.8 +/- 0.1 mL/kg and 6.3 +/- 0.1
      mL/kg for males and females, respectively. Our findings show that athletes may
      require additional Tv of 10% (0.6/6 mL/kg) for males and 8.3% (0.5/6 mL/kg) for
      females during general anesthesia and critical care which needs to be further
      investigated and tested.

PMID- 24288490
TI  - Parametric appraisal of process parameters for adhesion of plasma sprayed
      nanostructured YSZ coatings using Taguchi experimental design.
AB  - This paper presents the application of the Taguchi experimental design in
      developing nanostructured yittria stabilized zirconia (YSZ) coatings by plasma
      spraying process. This paper depicts dependence of adhesion strength of as
      sprayed nanostructured YSZ coatings on various process parameters, and effect of
      those process parameters on performance output has been studied using Taguchi's
      L16 orthogonal array design. Particle velocities prior to impacting the
      substrate, stand-off-distance, and particle temperature are found to be the most
      significant parameter affecting the bond strength. To achieve retention of
      nanostructure, molten state of nanoagglomerates (temperature and velocity) has
      been monitored using particle diagnostics tool. Maximum adhesion strength of
      40.56 MPa has been experimentally found out by selecting optimum levels of
      selected factors. The enhanced bond strength of nano-YSZ coating may be
      attributed to higher interfacial toughness due to cracks being interrupted by
      adherent nanozones.

PMID- 24288491
TI  - Involvement of MAPKs and PLC pathways in modulation of pacemaking activity by So
      Cheong-Ryong-Tang in interstitial cells of Cajal from murine small intestine.
AB  - PURPOSE: Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate
      slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the
      effects of Socheongryong-Tang (SCRT) in ICCs from mouse's small intestine.
      METHODS: The whole-cell patch-clamp configuration was used to record membrane
      potentials from cultured ICCs. Intracellular Ca(2+) ([Ca(2+)]i) increase was
      studied in cultured ICCs using fura-2 AM. RESULTS: ICCs generated pacemaker
      potentials in mouse's small intestine. SCRT produced membrane depolarization in
      current clamp mode. Y25130 (5-HT3 receptor antagonist) and RS39604 (5-HT4
      receptor antagonist) blocked SCRT-induced membrane depolarizations, whereas
      SB269970 (5-HT7 receptor antagonist) did not. When GDP- beta -S (1 mM) was in the
      pipette solution, SCRT did not induce the membrane depolarizations. [Ca(2+)]i
      analysis showed that SCRT increased [Ca(2+)]i. In the presence of PD98059 (p42/44
      MAPK inhibitor), SCRT did not produce membrane depolarizations. In addition,
      SB203580 (p38 MAPK inhibitor) and JNK inhibitors blocked the depolarizations by
      SCRT in pacemaker potentials. Furthermore, the membrane depolarizations by SCRT
      were not inhibited by U-73122, an active phospholipase C (PLC) inhibitor, but by
      U-73343, an inactive PLC inhibitor. CONCLUSION: These results suggest that SCRT
      might affect GI motility by the modulation of pacemaker activity through MAPKs
      and PLC pathways in the ICCs.

PMID- 24288492
TI  - Number size distribution of ambient particles in a typical urban site: the first
      Polish assessment based on long-term (9 months) measurements.
AB  - This work presents results from the long-term measurements of particle number
      carried out at an urban background station in Zabrze, Poland. Ambient particles
      with aerodynamic diameters of between 28 nm and 10 MU m were investigated by
      means of a DEKATI thirteen-stage electrical low pressure impactor (ELPI). The
      particle number-size distribution was bimodal, whilst its density function had
      the local maxima in the aerodynamic diameter intervals 0.056-0.095 MU m and 0.157
      0.263 MU m. The average particle number in winter was nearly twice as high as in
      summer. The greatest number concentrations in winter were those of the particles
      with diameters of between 0.617 and 2.41 MU m, that is, the anthropogenic
      particles from fossil fuel combustion. Approximately 99% of the particles
      observed in Zabrze had aerodynamic diameters <= 1 MU m-they may have originated
      from the combustion of biomass, liquid, and gaseous fuels in domestic stoves or
      in car engines. The daily variation of particle number was similar for both
      seasons-the highest values were observed in the morning (traffic rush hour) and
      in the afternoon/late evening (traffic and house heating emissions). An
      additional maximum (0.028-0.056 MU m) observed in the early afternoon in summer
      was due to the intensive formation of new PM particles from gas precursors.

PMID- 24288494
TI  - Efficacy of low-level laser therapy in the management of tinnitus due to noise
      induced hearing loss: a double-blind randomized clinical trial.
AB  - Background. Several remedial modalities for the treatment of tinnitus have been
      proposed, but an effective standard treatment is still to be confirmed. In the
      present study, we aimed to evaluate the effect of low-level laser therapy on
      tinnitus accompanied by noise-induced hearing loss. Methods. This was a double
      blind randomized clinical trial on subjects suffering from tinnitus accompanied
      by noise-induced hearing loss. The study intervention was 20 sessions of low
      level laser therapy every other day, 20 minutes each session. Tinnitus was
      assessed by three methods (visual analog scale, tinnitus handicap inventory, and
      tinnitus loudness) at baseline, immediately and 3 months after the intervention.
      Results. All subjects were male workers with age range of 30-51 years. The mean
      tinnitus duration was 1.85 +/- 0.78 years. All three measurement methods have
      shown improved values after laser therapy compared with the placebo both
      immediately and 3 months after treatment. Laser therapy revealed a U-shaped
      efficacy throughout the course of follow-up. Nonresponse rate of the intervention
      was 57% and 70% in the two assessment time points, respectively. Conclusion. This
      study found low-level laser therapy to be effective in alleviating tinnitus in
      patients with noise-induced hearing loss, although this effect has faded after 3
      months of follow-up. This trial is registered with the Australian New Zealand
      clinical trials registry with identifier ACTRN12612000455864). 

PMID- 24288495
TI  - Reestablishment of ischemia-reperfusion liver injury by N-acetylcysteine
      administration prior to a preconditioning iron protocol.
AB  - The role of iron (Fe)-induced prooxidant status in Fe preconditioning against
      ischemia (1 h)-reperfusion (20 h) induced liver injury was assessed using N
      acetylcysteine (NAC) (1 g/kg) before Fe (50 mg/kg), given to male Sprague Dawley
      rats on alternate days during 10 days. IR significantly increased serum aspartate
      transaminase (AST) and alanine transaminase (ALT) levels, with drastic changes in
      liver histology, hepatic glutathione depletion, and nuclear factor-kappaB (NF
      kappaB) p65 diminution (P < 0.05) (ELISA). Fe-induced liver oxidative stress, as
      evidenced by higher protein carbonyl/glutathione content ratios (P < 0.05) at
      days 11 and 12 after treatment, was abolished by NAC. Under these conditions,
      short-term Fe administration exerted significant protection against IR liver
      injury, as shown by 85% and 60% decreases in IR-induced serum AST and ALT (P <
      0.05), respectively, and normalization of hepatic histology, glutathione levels,
      and NF-kappaB activation, changes that were suppressed by NAC administration
      prior to Fe. Results of this study indicate that NAC administration prior to an
      iron protocol reestablishes IR liver injury, supporting the role of Fe-induced
      transient oxidative stress in hepatoprotection and its potential clinical
      application.

PMID- 24288496
TI  - Positive solutions of advanced differential systems.
AB  - We study asymptotic behavior of solutions of general advanced differential
      systems y(t) = F(t, y(t)), where F : Omega -> [Symbol: see text] (n) is a
      continuous quasi-bounded functional which satisfies a local Lipschitz condition
      with respect to the second argument and Omega is a subset in [Symbol: see text] *
      C(r)(n), C(r)(n) := C([0, r], [Symbol: see text] (n)), y t [Symbol: see
      text]C(r)(n), and y t (theta) = y(t + theta), theta [Symbol: see text] [0, r]. A
      monotone iterative method is proposed to prove the existence of a solution
      defined for t -> infinity with the graph coordinates lying between graph
      coordinates of two (lower and upper) auxiliary vector functions. This result is
      applied to scalar advanced linear differential equations. Criteria of existence
      of positive solutions are given and their asymptotic behavior is discussed.

PMID- 24288493
TI  - Periprosthetic joint infections: clinical and bench research.
AB  - Prosthetic joint infection is a devastating complication with high morbidity and
      substantial cost. The incidence is low but probably underestimated. Despite a
      significant basic and clinical research in this field, many questions concerning
      the definition of prosthetic infection as well the diagnosis and the management
      of these infections remained unanswered. We review the current literature about
      the new diagnostic methods, the management and the prevention of prosthetic joint
      infections. 

PMID- 24288497
TI  - Cytotoxic and apoptotic effects of different extracts of Artemisia turanica
      Krasch. on K562 and HL-60 cell lines.
AB  - Artemisia is an important genus of Iranian flora. Cytotoxic activities for some
      species of the genus have already been reported. In this study, we have
      investigated the cytotoxic effects of n-hexane, CH2Cl2, EtOAc, EtOH, and EtOH/H2O
      (1:1) extracts of A. turanica Krasch. on two human leukemic cancer cell lines
      (K562 and HL-60) and J774 as normal cells using alamarBlue (resazurin) assay. PI
      staining of the fragmented DNA and western blot analysis were used to evaluate
      the possible apoptotic effect of the extract. The CH2Cl2 extract of A. turanica
      showed the most antiproliferative effect on cancer cells among all tested
      extracts with IC50 values of 69 and 104 MU g/mL on K562 and HL-60 cells,
      respectively, whereas the normal cells were not affected significantly by this
      extract. Sub-G1 peak in the flow cytometry histogram of the cells treated with
      CH2Cl2 extract of A. turanica and cleavage of PARP protein confirmed the
      induction of apoptosis with CH2Cl2 extract. Taken together, the findings of the
      present work suggest the anticancer potential of CH2Cl2 extract of A. turanica on
      human leukemic cancer cell lines.

PMID- 24288498
TI  - Dendrimers as carriers for siRNA delivery and gene silencing: a review.
AB  - RNA interference (RNAi) was first literaturally reported in 1998 and has become
      rapidly a promising tool for therapeutic applications in gene therapy. In a
      typical RNAi process, small interfering RNAs (siRNA) are used to specifically
      downregulate the expression of the targeted gene, known as the term "gene
      silencing." One key point for successful gene silencing is to employ a safe and
      efficient siRNA delivery system. In this context, dendrimers are emerging as
      potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have
      attracted intense interest since their emanating research in the 1980s and are
      extensively studied as efficient DNA delivery vectors in gene transfer
      applications, due to their unique features based on the well-defined and
      multivalent structures. Knowing that DNA and RNA possess a similar structure in
      terms of nucleic acid framework and the electronegative nature, one can also use
      the excellent DNA delivery properties of dendrimers to develop effective siRNA
      delivery systems. In this review, the development of dendrimer-based siRNA
      delivery vectors is summarized, focusing on the vector features (siRNA delivery
      efficiency, cytotoxicity, etc.) of different types of dendrimers and the related
      investigations on structure-activity relationship to promote safe and efficient
      siRNA delivery system. 

PMID- 24288499
TI  - Acute mesenteric ischemia after cardiac surgery: an analysis of 52 patients.
AB  - OBJECTIVE: Acute mesenteric ischemia (AMI) is a rare but serious complication
      after cardiac surgery. The aim of this retrospective study was to evaluate the
      incidence, outcome, and perioperative risk factors of AMI in the patients
      undergoing elective cardiac surgery. METHODS: From January 2005 to May 2013, all
      patients who underwent cardiac surgery were screened for participation, and
      patients with registered gastrointestinal complications were retrospectively
      reviewed. Univariate analyses were performed. RESULTS: The study included 6013
      patients, of which 52 (0.86%) patients suffered from AMI, 35 (67%) of whom died.
      The control group (150 patients) was randomly chosen from among cases undergoing
      cardiopulmonary bypass (CPB). Preoperative parameters including age (P = 0.03),
      renal insufficiency (P = 0.004), peripheral vascular disease (P = 0.04),
      preoperative inotropic support (P < 0.001), poor left ventricular ejection
      fraction (P = 0.002), cardiogenic shock (P = 0.003), and preoperative intra
      aortic balloon pump (IABP) support (P = 0.05) revealed significantly higher
      levels in the AMI group. Among intra- and postoperative parameters, CPB time (P <
      0.001), dialysis (P = 0.04), inotropic support (P = 0.007), prolonged ventilator
      time (P < 0.001), and IABP support (P = 0.007) appeared significantly higher in
      the AMI group than the control group. CONCLUSIONS: Prompt diagnosis and early
      treatment should be initiated as early as possible in any patient suspected of
      AMI, leading to dramatic reduction in the mortality rate.

PMID- 24288500
TI  - Investigation of the presence of biofilms in chronic suppurative otitis media,
      nonsuppurative otitis media, and chronic otitis media with cholesteatoma by
      scanning electron microscopy.
AB  - OBJECTIVE: Biofilms have been shown to play a major role in the pathogenesis of
      otolaryngologic infections. However, very limited studies have been undertaken to
      demonstrate the presence of biofilms in tissues from patients with chronic otitis
      media (COM) with or without cholesteatoma. Our objective is to study the presence
      of biofilms in humans with chronic suppurative and nonsuppurative otitis media
      and cholesteatoma. Study Design. In all, 102 tissue specimens (middle ear,
      mastoid tissue, and ossicle samples) were collected during surgery from 34
      patients. METHODS: The samples were processed for the investigation of biofilms
      by scanning electron microscopy (SEM). RESULTS: Our research supports the
      hypothesis in which biofilms are involved in chronic suppurative otitis media,
      cholesteatoma, and, to a lesser degree, chronic nonsuppurative otitis media.
      There were higher rates in hypertrophic and granulated tissue samples than in
      normal mucosa. In addition, the presence of biofilms was significantly higher in
      the middle ear mucosa compared with the mastoid and ossicle samples. CONCLUSION:
      In the clinic, the careful use of topical or systemic antimicrobials is
      essential, and, during surgery, hypertrophic tissue must be carefully removed
      from normal tissue.

PMID- 24288501
TI  - Oxygen uptake in maximal effort constant rate and interval running.
AB  - This study investigated differences in average VO2 of maximal effort interval
      running to maximal effort constant rate running at lactate threshold matched for
      time. The average VO2 and distance covered of 10 recreational male runners
      (VO2max: 4158 +/- 390 mL . min(-1)) were compared between a maximal effort
      constant-rate run at lactate threshold (CRLT), a maximal effort interval run
      (INT) consisting of 2 min at VO2max speed with 2 minutes at 50% of VO2 repeated 5
      times, and a run at the average speed sustained during the interval run (CR
      submax). Data are presented as mean and 95% confidence intervals. The average VO2
      for INT, 3451 (3269-3633) mL . min(-1), 83% VO2max, was not significantly
      different to CRLT, 3464 (3285-3643) mL . min(-1), 84% VO2max, but both were
      significantly higher than CR sub-max, 3464 (3285-3643) mL . min(-1), 76% VO2max.
      The distance covered was significantly greater in CLRT, 4431 (4202-3731) metres,
      compared to INT and CR sub-max, 4070 (3831-4309) metres. The novel finding was
      that a 20-minute maximal effort constant rate run uses similar amounts of oxygen
      as a 20-minute maximal effort interval run despite the greater distance covered
      in the maximal effort constant-rate run.

PMID- 24288502
TI  - A review of data fusion techniques.
AB  - The integration of data and knowledge from several sources is known as data
      fusion. This paper summarizes the state of the data fusion field and describes
      the most relevant studies. We first enumerate and explain different
      classification schemes for data fusion. Then, the most common algorithms are
      reviewed. These methods and algorithms are presented using three different
      categories: (i) data association, (ii) state estimation, and (iii) decision
      fusion. 

PMID- 24288503
TI  - Alum catalyzed simple, efficient, and green synthesis of 2-[3-amino-5-methyl-5
      (pyridin-3-yl)-1,5-dihydro-4H-1,2,4-triazol-4-yl]propanoic acid derivatives in
      aqueous media.
AB  - Alum (KAl(SO4)2 . 12H2O) is an inexpensive, efficient, and nontoxic catalyst used
      for the synthesis of 2-[3-amino-5-methyl-5-(pyridin-3-yl)-1,5-dihydro-4H-1,2,4
      triazol-4-yl]propanoic acid derivatives in aqueous media by the reaction of 3
      acetyl pyridine (1), amino acids (2)/(6), and thiosemicarbazide (4) at 80 
      degrees C. This methodology offers significant improvements for the synthesis of
      products with regards to the yield of products, simplicity in operation, and
      green aspects by avoiding toxic catalysts which uphold the motto of green
      chemistry. Synthesized compounds have been characterized by FT-IR, (13)C NMR, and
      (1)HNMR spectroscopy.

PMID- 24288504
TI  - Smart caching based on mobile agent of power WebGIS platform.
AB  - Power information construction is developing towards intensive, platform,
      distributed direction with the expansion of power grid and improvement of
      information technology. In order to meet the trend, power WebGIS was designed and
      developed. In this paper, we first discuss the architecture and functionality of
      power WebGIS, and then we study caching technology in detail, which contains
      dynamic display cache model, caching structure based on mobile agent, and cache
      data model. We have designed experiments of different data capacity to contrast
      performance between WebGIS with the proposed caching model and traditional
      WebGIS. The experimental results showed that, with the same hardware environment,
      the response time of WebGIS with and without caching model increased as data
      capacity growing, while the larger the data was, the higher the performance of
      WebGIS with proposed caching model improved. 

PMID- 24288505
TI  - The determination of six ionophore coccidiostats in feed by liquid chromatography
      with postcolumn derivatisation and spectrofotometric/fluorescence detection.
AB  - The control of levels of anticoccidial feed additives in targeted feeds plays an
      important role in the assurance of efficiency of animal treatment, prevention of
      drug resistance, and food safety. The robust and labour-efficient method for the
      simultaneous determination of six ionophore coccidiostats (lasalocid,
      maduramicin, monensin, narasin, salinomycin, and semduramicin) in targeted feed
      has been developed. Properly grinded and homogenized feed sample was spiked with
      internal standard (monesin methyl ester) and extracted with methanol. The extract
      was analysed with reversed phase HPLC without any further purification. The
      separation of the analytes with conventional C18 and core-shell columns was
      compared. Lasalocid was analysed with fluorescence detection, whereas other
      ionophores were detected with UV-Vis detector after derivatisation with vanillin
      in the presence of sulfuric acid. Fortified samples and targeted feeds at
      authorized levels were used for method validation. Recovery was in the range of
      85-110%, depending on the analyte. The within-laboratory reproducibility did not
      exceed the target value from Horwitz equation. The results of the proficiency
      tests (z-scores in the range of -1.0 to 1.9) confirmed the reliability of the
      developed protocol. 

PMID- 24288506
TI  - Some new algebraic and topological properties of the Minkowski inverse in the
      Minkowski space.
AB  - We introduce some new algebraic and topological properties of the Minkowski
      inverse A([Symbol: see text) of an arbitrary matrix A[Symbol: see text] M m,n
      (including singular and rectangular) in a Minkowski space MU. Furthermore, we
      show that the Minkowski inverse A ([Symbol: see text]) in a Minkowski space and
      the Moore-Penrose inverse A(+) in a Hilbert space are different in many
      properties such as the existence, continuity, norm, and SVD. New conditions of
      the Minkowski inverse are also given. These conditions are related to the
      existence, continuity, and reverse order law. Finally, a new representation of
      the Minkowski inverse A ([Symbol: see text]) is also derived.

PMID- 24288507
TI  - A clustering protocol for wireless sensor networks based on energy potential
      field.
AB  - It is the core issue of researching that how to prolong the lifetime of wireless
      sensor network. The purpose of this paper is to illustrate a clustering protocol
      LEACH-PF, which is a multihop routing algorithm with energy potential field of
      divided clusters. In LEACH-PF, the network is divided into a number of
      subnetworks and each subnetwork has a cluster head. These clusters construct an
      intercluster routing tree according to the potential difference of different
      equipotential fields. The other member nodes of the subnetworks communicate with
      their cluster head directly, so as to complete regional coverage. The results of
      simulation show that LEACH-PF can reduce energy consumption of the network
      effectively and prolong the network lifetime. 

PMID- 24288508
TI  - Static and dynamic electronic (hyper)polarizabilities of dimethylnaphthalene
      isomers: characterization of spatial contributions by density analysis.
AB  - Static and frequency-dependent electronic (hyper)polarizabilities of the
      dimethylnaphthalene (DMN) isomers were computed in vacuum using the Coulomb
      attenuating Density Functional Theory method. The nonlinear optical Second
      Harmonic Generation (SHG) and Electro-Optical Pockels Effect (EOPE) were
      investigated at the characteristic Nd:YAG laser wavelength of 1064 nm. The
      response electric properties especially the longitudinal polarizability,
      polarizability anisotropy, and first-order hyperpolarizability are significantly
      affected by the position of the methyl groups. The SHG and EOPE techniques can be
      potentially useful to discriminate the alpha,alpha-DMN isomers (2,6-DMN < 2,7-DMN
      < 2,3-DMN) as well as the beta,beta-DMN isomers (1,5-DMN < 1,4-DMN < 1,8-DMN).
      The (hyper)polarizability differences among the investigated DMNs were elucidated
      through density analysis calculations. The predicted polarizabilities exhibit
      good linear relationships with the experimental first-order biomass-normalized
      rate coefficient, a physicochemical property connected to the rates of
      biodegradation processes of polycyclic aromatic hydrocarbons.

PMID- 24288509
TI  - Nutritional composition and antioxidant properties of Cucumis dipsaceus Ehrenb.
      ex Spach leaf.
AB  - The leaf of C. dipsaceus was evaluated for its nutritional and antioxidant
      properties. From the present investigation, significant amount of almost all
      essential amino acids and important minerals were quantified. Low levels of
      trypsin inhibitory units, phenolics, and tannins content were found as
      antinutritional content. Further, hot water extract of C. dipsaceus showed good
      activity especially in ABTS(+), metal chelating, nitric oxide, and DPPH assays.
      Hence, the results conclude that C. dipsaceus could be a valuable nutraceutical
      supplement to the human diet. 

PMID- 24288510
TI  - Association between cysticercosis and neoplasia: a study based on autopsy
      findings.
AB  - Chronic infections including the cysticercosis induce inflammatory cells to
      produce free radicals and synthesize carcinogenic toxins. The cells with genetic
      mutations proliferate in a disorganized manner, leading to the development of
      neoplasia. The aim of the present study was to demonstrate the relation between
      cysticercosis and neoplasia. Patients autopsied were divided into 4 groups:
      patients with neoplasia and cysticercosis (NC), patients with neoplasia only
      (NN), patients with cysticercosis only (CC), and patients without neoplasia or
      cysticercosis (WW). Of 2012 autopsy reports analyzed, 0.4 showed NC. In groups CC
      and NC, the most common location of the parasite was the brain. There was a
      predominance of three or more cysticerci in groups NC and CC. In the NC group,
      all had malignant neoplasms, and was predominance of benign neoplasm in NN group.
      The digestive system was the most frequent neoplasia. By calculating odds ratio,
      rate of neoplasia in patients with cysticercosis was 0.74. In conclusion, the
      demographic profile of patients with cysticercosis and neoplasia is similar to
      that of patients with cysticercosis alone. The incidence of cysticercosis and
      neoplasia was greater in older patients suggesting that immunosenescence may
      contribute to development of neoplasia promoted by cysticercosis. 

PMID- 24288511
TI  - Association of psoriasis severity with serum prolactin, thyroid hormones, and
      cortisol before and after treatment.
AB  - BACKGROUND: Prolactin (PRL) level is proposed to be associated with the severity
      of psoriasis although the previous studies reported different results. OBJECTIVE:
      To find the association between PRL levels and severity of psoriasis before and
      after treatment. In addition, we aimed to find a difference in prolactin, thyroid
      stimulating hormone (TSH), thyroid hormones (T3 and T4), and cortisol levels
      between patients with psoriasis and normal controls. METHODS: First, the levels
      of hormones were measured in 30 patients with psoriasis and 30 matched controls.
      The severity was assessed by psoriasis area and severity index (PASI). Then,
      patients were treated, and PASI was assessed every week until achieving PASI-75
      response. At this time, the hormones were measured again and compared to the
      baseline. RESULTS: No statistical significant difference was observed in the mean
      PRL, T3, T4, TSH, and cortisol levels between cases and controls. Comparing to
      the baseline, a significant decrease in PRL levels and a significant increase in
      T3 and serum cortisol levels were observed after treatment (P < 0.05), while the
      changes in other hormones were not significant. CONCLUSION: After treatment, PRL
      significantly decreased, and T3 and cortisol levels significantly increased. No
      correlation between hormone levels and improvement of PASI score existed.

PMID- 24288512
TI  - Efficacy of memantine, donepezil, or their association in moderate-severe
      Alzheimer's disease: a review of clinical trials.
AB  - BACKGROUND: Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and
      memantine are licensed for symptomatic treatment of mild-moderate and moderate
      severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I
      donepezil were licensed in the USA for moderate-severe AD, and the association
      AChE/ChE-Is plus memantine was proposed for AD at this stage. OBJECTIVES: This
      paper has reviewed evidence from clinical trials of the effectiveness of
      memantine, donepezil, or the two drugs in association in managing moderate-severe
      AD. METHOD: Double-blind, placebo-controlled randomized trials (RCTs) using
      memantine or donepezil alone or in association versus placebo in moderate-severe
      AD were reviewed. Analysis done in January 2013 considered the years 2007-2012.
      RESULTS AND CONCLUSION: Only 83 of the 941 papers selected were considered
      relevant, and only 13 met the criterion of "adequacy and representativeness."
      Memantine and donepezil lead to improvements in moderate-to-severe AD and the
      choice between the compounds should be based on their contraindications more than
      on disease severity. No evidence was found of advantages of the association of
      memantine-donepezil. The heterogeneity of conditions explored by RCTs, the
      relatively short time of observation (24-52 weeks), and the different cognitive
      assessment tools used did not allow comparing properly different trials.

PMID- 24288513
TI  - Echocardiographic assessment of cardiac structural and functional indices in
      broiler chickens treated with silver nanoparticles.
AB  - 270 Ross broiler chickens of twenty days old were housed in 18-floor pens in a
      completely randomized design with six treatment groups and three replicate groups
      and fifteen chicks per each pen. The treatment groups (1-6) consisted of 0, 10,
      20, 30, 50, and 70 ppm of nanocide in drinking water, respectively. At 26 days of
      age, 3 chickens were selected randomly for echocardiography using a 7.5 MHz
      linear probe, and the left ventricular internal diameter at the end of diastole
      (LVIDd), left ventricular internal diameter at the end of systole (LVIDs), left
      ventricular fractional shortening (LVFS), ejection fraction (EF), stroke volume
      (SV), interventricular septum thickness at the end of systole (IVSTs), and
      interventricular septum thickness at the end of diastole (IVSTd) were evaluated.
      LVIDd and LVIDs in group six were of higher rate than other groups and showed
      statistically significant differences with groups two, three, and four (P <
      0.05). LVFS, percentage of EF, and IVSTd were minimum in group six and had
      significant difference with other groups (P < 0.05). The results of this study
      showed that prescription of high dosage of nanocide leads to cardiovascular
      problems with decrease in myocardial contractility and increase in the internal
      diameter of left ventricle.

PMID- 24288514
TI  - Population studies and carrageenan properties in eight Gigartinales (Rhodophyta)
      from Western Coast of Portugal.
AB  - Eight carrageenophytes, representing seven genera and three families of
      Gigartinales (Florideophyceae), were studied for 15 months. The reproductive
      status, dry weight, and carrageenan content have been followed by a monthly
      random sampling. The highest carrageenan yields were found in Chondracanthus
      acicularis (61.1%), Gigartina pistillata (59.7%), and Chondracanthus teedei var.
      lusitanicus (58.0%). Species of Cystocloniaceae family produces predominantly
      iota-carrageenans; Gigartinaceae family produces hybrid kappa-iota carrageenans
      (gametophytic plants) and lambda-family carrageenans (sporophytic plants);
      Phyllophoraceae family produces kappa-iota-hybrid carrageenans. Quadrate
      destructive sampling method was used to determine the biomass and line transect.
      Quadrate nondestructive sampling method, applied along a perpendicular transect
      to the shoreline, was used to calculate the carrageenophytes cover in two
      periods: autumn/winter and spring/summer. The highest cover and biomass were
      found in Chondrus crispus (3.75%-570 g/m(2)), Chondracanthus acicularis (3.45%-99
      g/m(2)), Chondracanthus teedei var. lusitanicus (2.45%-207.5 g/m(2)), and
      Mastocarpus stellatus (2.02%-520 g/m(2)).

PMID- 24288515
TI  - Certain subclasses of analytic functions with complex order.
AB  - Two new subclasses of analytic functions of complex order are introduced. Apart
      from establishing coefficient bounds for these classes, we establish inclusion
      relationships involving (n-delta) neighborhoods of analytic functions with
      negative coefficients belonging to these subclasses. 

PMID- 24288516
TI  - A planar-dimensions machine vision measurement method based on lens distortion
      correction.
AB  - Lens distortion practically presents in a real optical imaging system causing
      nonuniform geometric distortion in the images and gives rise to additional errors
      in the vision measurement. In this paper, a planar-dimensions vision measurement
      method is proposed by improving camera calibration, in which the lens distortion
      is corrected on the pixel plane of image. The method can be divided into three
      steps: firstly, the feature points, only in the small central region of the
      image, are used to get a more accurate perspective projection model; secondly,
      rather than defining a uniform model, the smoothing spline function is used to
      describe the lens distortion in the measurement region of image, and two
      correction functions can be obtained by fitting two deviation surfaces; finally,
      a measurement method for planar dimensions is proposed, in which accurate
      magnification factor of imaging system can be obtained by using the correction
      functions. The effectiveness of the method is demonstrated by applying the
      proposed method to the test of measuring shaft diameter. Experimental data prove
      that the accurate planar-dimensions measurements can be performed using the
      proposed method even if images are deformed by lens distortion. 

PMID- 24288517
TI  - Risk factors associated with the occurrence of the second-litter syndrome in sows
      in southeastern Mexico.
AB  - The objective was to estimate the incidence of and to determine the effect of
      some risk factors on the decrease of litter size at parity 2 of sows in three
      commercial farms in Yucatan, Mexico. Data on 8,592 farrowing records of 4,296
      sows were analyzed using a binomial logistic regression procedure. The model
      included the fixed effect of farm (1, 2, and 3), year of farrowing (2003-2011),
      season of farrowing (dry, rainy, and windy), number of pigs born alive at first
      parity (<9, 9-10, 11-12, and >12 piglets), lactation length (<18, 18-24, and >24
      days), and weaning to conception intervals (<4, 4-11, and >11 days). Fifty-five
      point eight percent of all sows presented a reduced or similar litter size at
      parity 2. The odds of decrease in the second litter size were 1.56 and 2.01 for
      farms 2 and 3, respectively. Higher odds were found for sows farrowing during the
      rainy and dry seasons (1.20 and 1.24, resp.) and for sows with large litters at
      parity 1 (>12 piglets, odds = 33.2). Sows with weaning to conception intervals <4
      days and between 4 and 11 days had higher odds of a decrease in the second litter
      (1.78 and 2.74 pigs, resp.). 

PMID- 24288518
TI  - The vertebral column, ribs, and sternum of the African giant rat (Cricetomys
      gambianus waterhouse).
AB  - Examined bones were obtained from eight adult African giant rats, Cricetomys
      gambianus Waterhouse. Animals used had an average body mass of 730.00 +/- 41.91
      gm and body length of 67.20 +/- 0.05 cm. The vertebral formula was found to be
      C7, T13, L6, S4, Ca31-36. The lowest and highest points of the cervicothoracic
      curvature were at C5 and T2, respectively. The spinous process of the axis was
      the largest in the cervical group while others were sharp and pointed. The
      greatest diameter of the vertebral canal was at the atlas (0.8 cm) and the lowest
      at the caudal sacral bones (2 mm). The diameter of the vertebral foramen was the
      largest at C1 and the smallest at the S4; the foramina were negligibly indistinct
      caudal to the sacral vertebrae. There were 13 pairs of ribs. The first seven
      pairs were sternal, and six pairs were asternal of which the last 2-3 pairs were
      floating ribs. The sternum was composed of deltoid-shaped manubrium sterni, four
      sternebrae, and a slender processus xiphoideus. No sex-related differences were
      observed. The vertebral column is adapted for strong muscular attachment and
      actions helping the rodent suited for speed, agility, dexterity, and strength
      which might enable it to overpower prey and escape predation.

PMID- 24288519
TI  - On the stability of one-dimensional wave equation.
AB  - We prove the generalized Hyers-Ulam stability of the one-dimensional wave
      equation, u(tt) = c(2)u(xx), in a class of twice continuously differentiable
      functions.

PMID- 24288520
TI  - Clinical implications of Girdin protein expression in glioma.
AB  - OBJECTIVE: To investigate the expression status of Girdin in glioma and the
      relationship between Girdin expression and the biological behavior of glioma.
      MATERIALS AND METHODS: The expression status of Girdin in glioma from 560 cases
      was evaluated by RT-PCR, Western Blot and immunohistochemistry. The relationship
      between Girdin expression and clinic-pathological parameters as well as prognosis
      was also studied. RESULTS: The expression of Girdin in high grade glioma was
      significantly higher than low grade glioma. After universal analysis, the
      expression of Girdin protein is closely related to KPS score, extent of
      resection, Ki67 and WHO grade, but it was not related to sex and age. Finally,
      extent of resection, Ki67 and WHO grade were indentified to be related to the
      Girdin protein expression in logistic regression. Interestingly, we found that
      the expression of Girdin is significantly related to the distant metastasis of
      glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO
      grade as well as Girdin were observed to be independent prognostic factors.
      CONCLUSIONS: Girdin is differential expressed in the glioma patients and closely
      related to the biological behavior of Glioma. Finally, Girdin was found to be a
      strong predictor for the post-operative prognosis.

PMID- 24288521
TI  - Addressing Health Disparities among Men: Demographic, Behavioral and Clinical
      Characteristics of Men who have Sex with Men Living in Puerto Rico.
AB  - The objective of this study was to compare sociodemographic, behavioral and
      clinical characteristics associated with HIV among Men who have sex with Men
      (MSM) and men who have sex with women (MSW) in Puerto Rico. Data from a
      population-based cross-sectional study in PR (2005-2008) was analyzed.
      Descriptive statistics were used to describe the study sample and bivariate
      analyses were performed to identify differences of sociodemographic, behavioral
      and clinical characteristics between MSM and MSW. Exact logistic regression
      models adjusting for age were constructed for each risk behavior associated to
      MSM in bivariate analysis. Of the 674 men interviewed, 6.1% (n=41) reported ever
      having sex with men. Age-adjusted logistic regression models indicated that MSM
      were significantly more likely than MSW to have first sexual intercourse before
      the age of 15 (POR=2.6; 95%CI= 1.3, 5.3) and have at least 10 lifetime sex
      partners (POR=2.8; 95%CI= 1.4,5.9). Also, MSM were significantly more likely to
      report lifetime use of marihuana (POR=2.7; 95%CI= 1.3,5.8), cocaine (POR=2.5;
      95%CI= 1.2,5.0), amphetamines (POR=3.8; 95%CI= 1.4,9.2) and sedatives or
      tranquilizers (POR=3.3; 95%CI= 1.4,7.2). Also, MSM were 13 times more likely to
      be HIV seropositive as compared to MSW (POR=13.3; 95%CI=1.7,102.0). In this
      population-based sample of men living in Puerto Rico, self-reported same-sex
      behavior is strongly associated with HIV, and other behavioral factors associated
      with HIV. Future targeted research is still necessary for the development of
      intervention programs among MSM in Puerto Rico.

PMID- 24288523
TI  - Measurement of intervertebral cervical motion by means of dynamic x-ray image
      processing and data interpolation.
AB  - Accurate measurement of intervertebral kinematics of the cervical spine can
      support the diagnosis of widespread diseases related to neck pain, such as
      chronic whiplash dysfunction, arthritis, and segmental degeneration. The natural
      inaccessibility of the spine, its complex anatomy, and the small range of motion
      only permit concise measurement in vivo. Low dose X-ray fluoroscopy allows time
      continuous screening of cervical spine during patient's spontaneous motion. To
      obtain accurate motion measurements, each vertebra was tracked by means of image
      processing along a sequence of radiographic images. To obtain a time-continuous
      representation of motion and to reduce noise in the experimental data, smoothing
      spline interpolation was used. Estimation of intervertebral motion for cervical
      segments was obtained by processing patient's fluoroscopic sequence;
      intervertebral angle and displacement and the instantaneous centre of rotation
      were computed. The RMS value of fitting errors resulted in about 0.2 degree for
      rotation and 0.2 mm for displacements. 

PMID- 24288522
TI  - The Neuropsychopharmacology of Pathological Gambling.
AB  - Pathological gambling (PG) is an impulse control disorder with prevalence
      estimates in the range of 0.2-2% in the general population. PG can significantly
      impact one's ability to function as it may negatively influence social,
      financial, and occupational aspects of life. Historically, PG has received
      relatively little attention from researchers and clinicians, and few treatments,
      particularly pharmacological, have been both validated and widely employed. Given
      the clinical relevance of PG, it is important that researchers examine
      pharmacological and behavioral treatments for their safety and efficacy and that
      clinicians use empirically validated therapies. Multiple neurochemicals,
      including serotonin, dopamine, norepinephrine, and opioids, and related
      neurocircuitry, particularly ventral cortico-striatal pathways, have been
      implicated in PG. The neurobiological rationale for therapies, particularly
      pharmacological ones, is reviewed with a perspective on the generation of
      improved prevention and treatment strategies for PG.

PMID- 24288524
TI  - PPARgamma-Dependent Control of Renin Expression: Molecular Mechanisms and
      Pathophysiological Relevance.
AB  - During the last years accumulating evidence demonstrated that the nuclear
      receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates
      the expression of renin gene and thus the overall renin production. This review
      summarizes the current knowledge of the transcriptional control of the renin gene
      by PPARgamma received from variety of models ranging from cell culture to
      transgenic animals. The molecular mechanisms of the PPARgamma action on renin are
      particularly interesting because they are featured by two newly described
      characteristics: one of them is the recently identified PPARgamma target sequence
      Pal3 which is specific for the human renin gene and mediates exceptionally high
      sensitivity to transactivation; the other is the potentiating effect of PPARgamma
      on the cAMP signaling in the renin-producing cells. Furthermore, I discuss the
      need for generating of additional transgenic animal models which are more
      appropriate with regard to the role of the PPARgamma-dependent regulation of the
      renin gene expression in human diseases such as arterial hypertension and
      metabolic syndrome. 

PMID- 24288525
TI  - Polymorphisms in PPAR Genes (PPARD, PPARG, and PPARGC1A) and the Risk of Chronic
      Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study.
AB  - Chronic kidney disease (CKD) is well known as a strong risk factor for both end
      stage renal disease and cardiovascular disease. To clarify the association of
      polymorphisms in the PPAR genes (PPARD, PPARG, and PPARGC1A) with the risk of CKD
      in Japanese, we examined this association among the Japanese subjects using the
      cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort)
      Study. The subjects for this analysis were 3,285 men and women, aged 35-69 years,
      selected from J-MICC Study participants; genotyping was conducted by multiplex
      polymerase chain reaction-based Invader assay. The prevalence of CKD was
      determined for CKD stages 3-5 (defined as eGFR < 60 ml/min/1.73 m(2)).
      Participants with CKD accounted for 17.3% of the study population. When those
      with PPARD T-842C T/T were defined as reference, those with PPARD T-842C T/C and
      C/C demonstrated the OR for CKD of 1.26 (95%CI 1.04-1.53) and 1.31 (95%CI 0.83
      2.06), respectively. There were no significant associations between the
      polymorphisms in other PPAR genes and the risk of CKD. The present study found a
      significantly increased risk of CKD in those with the C allele of PPARD T-842C,
      which may suggest the possibility of personalized risk estimation of this life
      limiting disease in the near future. 

PMID- 24288526
TI  - Wt-1 Expression Linked to Nitric Oxide Availability during Neonatal Obstructive
      Nephropathy.
AB  - The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a
      transcriptional activator or repressor depending on the cellular or chromosomal
      context. The wt-1 regulates the expression of a large number of genes that have a
      critical role in kidney development. Congenital obstructive nephropathy disrupts
      normal renal development and causes chronic progressive interstitial fibrosis,
      which contributes to renal growth arrest, ultimately leading to chronic renal
      failure. Wt-1 is downregulated during congenital obstructive nephropathy, leading
      to apoptosis. Of great interest, nitric oxide bioavailability associated with
      heat shock protein 70 (Hsp70) interaction may modulate wt-1 mRNA expression,
      preventing obstruction-induced cell death during neonatal unilateral ureteral
      obstruction. Moreover, recent genetic researches have allowed characterization of
      many of the complex interactions among the individual components cited, but the
      realization of new biochemical, molecular, and functional experiments as proposed
      in our and other research labs allows us to establish a deeper level of
      commitment among proteins involved and the potential pathogenic consequences of
      their imbalance. 

PMID- 24288527
TI  - Damage of stone baskets by endourologic lithotripters: a laboratory study of 5
      lithotripters and 4 basket types.
AB  - Background. In some cases, the ureteral stone is simultaneously stabilized by a
      stone basket when endourologic lithotripsy is performed. This stabilization can
      be either on purpose or by accident. By accident means that an impaction in the
      ureter occurs by an extraction of a stone with a basket. A stabilization on
      purpose means to avoid a retropulsion of the stone into the kidney during
      lithotripsy. At this part of the operation, stone baskets have been frequently
      damaged. This severing of wires can lead to ureteral trauma because of hook
      formation. Material and Methods. In a laboratory setting, the time and the pulse
      numbers were measured until breaking the wires from four different nitinol stone
      baskets by using five different lithotripsy devices. The endpoint was gross
      visibledamage to the wire and loss of electric conduction. Results. The Ho:YAG
      laser and the ultrasonic device were able to destroy almost all the wires. The
      ballistic devices and the electrohydraulic device were able to destroy thin
      wires. Conclusion. The operating surgeon should know the risk of damagefor every
      lithotripter. The Ho:YAG-laser and the ultrasonic device should be classified as
      dangerous for the basket wire with all adverse effects to the patient. 

PMID- 24288528
TI  - Higher prostate weight is inversely associated with Gleason score upgrading in
      radical prostatectomy specimens.
AB  - Background. Protective factors against Gleason upgrading and its impact on
      outcomes after surgery warrant better definition. Patients and Methods.
      Consecutive 343 patients were categorized at biopsy (BGS) and prostatectomy (PGS)
      as Gleason score, <=6, 7, and >=8; 94 patients (27.4%) had PSA recurrence, mean
      followup 80.2 months (median 99). Independent predictors of Gleason upgrading
      (logistic regression) and disease-free survival (DFS) (Kaplan-Meier, log-rank)
      were determined. Results. Gleason discordance was 45.7% (37.32% upgrading and
      8.45% downgrading). Upgrading risk decreased by 2.4% for each 1 g of prostate
      weight increment, while it increased by 10.2% for every 1 ng/mL of PSA, 72.0% for
      every 0.1 unity of PSA density and was 21 times higher for those with BGS 7.
      Gleason upgrading showed increased clinical stage (P = 0.019), higher tumor
      extent (P = 0.009), extraprostatic extension (P = 0.04), positive surgical
      margins (P < 0.001), seminal vesicle invasion (P = 0.003), less "insignificant"
      tumors (P < 0.001), and also worse DFS, chi (2) = 4.28, df = 1, P = 0.039.
      However, when setting the final Gleason score (BGS <=6 to PGS 7 versus BGS 7 to
      PGS 7), avoiding allocation bias, DFS impact is not confirmed, chi (2) = 0.40, df
      = 1, P = 0.530.Conclusions. Gleason upgrading is substantial and confers worse
      outcomes. Prostate weight is inversely related to upgrading and its protective
      effect warrants further evaluation. 

PMID- 24288529
TI  - Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor- kappa B Ligand,
      and Subclinical Atherosclerosis in Children and Adolescents with Type 1 Diabetes
      Mellitus.
AB  - Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the
      osteoprotegerin/receptor activator of nuclear factor- kappa B ligand (OPG/RANKL)
      system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects
      and Methods. Fifty six T1DM patients (mean +/- SD age: 12.0 +/- 2.7 years,
      diabetes duration: 5.42 +/- 2.87 years and HbA1c: 8.0 +/- 1.5%) and 28 healthy
      matched controls, were studied with anthropometric and laboratory measurements,
      including serum OPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric,
      laboratory, and cIMT measurements were similar between T1DM youngsters and
      controls. However patients with longer diabetes duration (>/7.0 years) had
      indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P 0.072) and triglyceride
      levels than the rest of the patients (93.7 vs 64.6 mg/dl, P 0.025). Both in the
      total study population (beta 0.418, P 0.027) and among T1DM patients separately
      (beta 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was
      further associated with OPG in both groups (beta -0.335, P 0.003 and beta -0.356,
      P 0.008 respectively), while sRANKL levels were not associated with any factor.
      Conclusions. BMI was the strongest independent predictor of cIMT among the whole
      population, and especially in diabetics, suggesting a possible synergistic effect
      of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly
      associated with circulating OPG, but the causes of this association remain
      unclear. 

PMID- 24288530
TI  - Trends in prevalence, awareness, treatment, and control of diabetes mellitus in
      mainland china from 1979 to 2012.
AB  - Diabetes mellitus (DM) is one of the primary causes of premature death and
      disability worldwide. We performed a systematic review and meta-analysis of the
      published literature regarding the trends in prevalence, awareness, treatment,
      and control of diabetes mellitus in mainland China. PUBMED, EMBASE, Chinese
      Biomedical Database, China National Infrastructure database, Chinese Wan Fang
      database, and Chongqing VIP database were searched. Fifty-six eligible studies
      were included. Increasing trends in the prevalence, treatment, and control of
      diabetes in mainland China from 1979 to 2012 were observed. The pooled
      prevalence, awareness, treatment, and control of diabetes mellitus were 6.41%,
      45.81%, 42.54%, and 20.87%, respectively. A higher prevalence of diabetes
      mellitus was found in urban (7.48%, 95%CI = 5.45~9.50) than rural (6.53%, 95%CI =
      4.30~8.76) areas. Furthermore, an increasing chronological tendency was shown in
      different subgroups of age with regard to the prevalence of diabetes. A higher
      awareness of DM was found in urban (44.25%, 95%CI = 32.60~55.90) than rural
      (34.27%, 95%CI = 21.00~47.54) populations, and no significant differences were
      found in the treatment, and control of diabetes among the subgroups stratified by
      gender and location. From 1979 to 2012, the prevalence, treatment, and control of
      diabetes mellitus increased; nevertheless, there was no obvious improvement in
      the awareness of diabetes. 

PMID- 24288532
TI  - Elucidating the interacting domains of chandipura virus nucleocapsid protein.
AB  - The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in
      viral life cycle, besides being an important structural component of the virion
      through proper organization of its interactions with other viral proteins. In a
      recent study, the authors had mapped the associations among CHPV proteins and
      shown that N protein interacts with four of the viral proteins: N, phosphoprotein
      (P), matrix protein (M), and glycoprotein (G). The present study aimed to
      distinguish the regions of CHPV N protein responsible for its interactions with
      other viral proteins. In this direction, we have generated the structure of CHPV
      N protein by homology modeling using SWISS-MODEL workspace and Accelrys Discovery
      Studio client 2.55 and mapped the domains of N protein using PiSQRD. The
      interactions of N protein fragments with other proteins were determined by ZDOCK
      rigid-body docking method and validated by yeast two-hybrid and ELISA. The study
      revealed a unique binding site, comprising of amino acids 1-30 at the N terminus
      of the nucleocapsid protein (N1) that is instrumental in its interactions with N,
      P, M, and G proteins. It was also observed that N2 associates with N and G
      proteins while N3 interacts with N, P, and M proteins. 

PMID- 24288531
TI  - Obesity-related metabolic syndrome: mechanisms of sympathetic overactivity.
AB  - The prevalence of the metabolic syndrome has increased worldwide over the past
      few years. Sympathetic nervous system overactivity is a key mechanism leading to
      hypertension in patients with the metabolic syndrome. Sympathetic activation can
      be triggered by reflex mechanisms as arterial baroreceptor impairment, by
      metabolic factors as insulin resistance, and by dysregulated adipokine production
      and secretion from visceral fat with a mainly permissive role of leptin and
      antagonist role of adiponectin. Chronic sympathetic nervous system overactivity
      contributes to a further decline of insulin sensitivity and creates a vicious
      circle that may contribute to the development of hypertension and of the
      metabolic syndrome and favor cardiovascular and kidney disease. Selective renal
      denervation is an emerging area of interest in the clinical management of obesity
      related hypertension. This review focuses on current understanding of some
      mechanisms through which sympathetic overactivity may be interlaced to the
      metabolic syndrome, with particular regard to the role of insulin resistance and
      of some adipokines. 

PMID- 24288533
TI  - A proposed model for infant and child oral health promotion in India.
AB  - Dental caries is an increasing burden in the developing countries. A proper
      budgetary allocation for treating dental diseases in an enormous population such
      as India is impractical, where resources are inadequate for major health
      challenges such as malnutrition and gastrointestinal and respiratory infections
      in children. An integrated, directed population approach targeting children is
      much needed. The existing machinery of successful public health campaigns such as
      the "Pulse Polio" and the "Mid-Day-Meals Scheme" of the Government of India can
      be used for oral health promotion for children. India has about 300 dental
      colleges and countrywide branches of the Indian Dental Association that can
      provide manpower for the program. An innovative, large-scale "Fit for School"
      program in Philippines is a model for an integrated approach for children's
      health and has proved to be cost-effective and viable. A model for oral health
      promotion in infants and children of India, combining age-specific initiatives
      for health education, nutrition, hygiene, and fluoride use, is proposed. The
      model could be implemented to evaluate the oral health status of children,
      knowledge and knowledge gain of the community health workers, and acceptability
      and sustainability of the preventive programs (fluoride varnish and preschool and
      school tooth brushing) pragmatically. 

PMID- 24288534
TI  - Isolation and screening of polyhydroxyalkanoates producing bacteria from pulp,
      paper, and cardboard industry wastes.
AB  - Background. Polyhydroxyalkanoates (PHAs) are storage materials that accumulate by
      various bacteria as energy and carbon reserve materials. They are biodegradable,
      environmentally friendly, and also biocompatible bioplastics. Unlike
      petrochemical-based plastics that take several decades to fully degrade, PHAs can
      be completely degraded within a year by variety of microorganisms into CO2 and
      water. In the present study, we aim to utilize pulp, paper, and cardboard
      industry sludge and waste water for the isolation and screening of
      polyhydroxyalkanoates (PHAs) accumulating bacteria and production of cost
      effective PHB using cardboard industry waste water. Results. A total of 42
      isolates showed black-blue coloration when stained with Sudan black B, a
      preliminary screening agent for lipophilic compounds, and a total of 15 isolates
      showed positive result with Nile blue A staining, a more specific dye for PHA
      granules. The isolates NAP11 and NAC1 showed maximum PHA production 79.27% and
      77.63% with polymer concentration of 5.236 g/L and 4.042 g/L with cardboard
      industry waste water. Both of the selected isolates, NAP11 and NAC1, were
      classified up to genus level by studying their morphological and biochemical
      characteristics and were found to be Enterococcus sp., Brevundimonas sp. and,
      respectively. Conclusion. The isolates Enterococcus sp. NAP11 and Brevundimonas
      sp. NAC1 can be considered as good candidates for industrial production of PHB
      from cardboard industry waste water. We are reporting for the first time the use
      of cardboard industry waste water as a cultivation medium for the PHB production.

PMID- 24288535
TI  - Modulation of vascular cell function by bim expression.
AB  - Apoptosis of vascular cells, including pericytes and endothelial cells,
      contributes to disease pathogenesis in which vascular rarefaction plays a central
      role. Bim is a proapoptotic protein that modulates not only apoptosis but also
      cellular functions such as migration and extracellular matrix (ECM) protein
      expression. Endothelial cells and pericytes each make a unique contribution to
      vascular formation and function although the details require further delineation.
      Here we set out to determine the cell autonomous impact of Bim expression on
      retinal endothelial cell and pericyte function using cells prepared from Bim
      deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased
      production of ECM proteins, proliferation, migration, adhesion, and VEGF
      expression but, a decreased eNOS expression and nitric oxide production. In
      contrast, pericyte proliferation decreased in the absence of Bim while migration,
      adhesion, and VEGF expression were increased. In addition, we demonstrated that
      the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-)
      pericytes diminished their capillary morphogenesis. Thus, our data further
      emphasizes the importance of vascular cell autonomous regulatory mechanisms in
      modulation of vascular function. 

PMID- 24288536
TI  - Management of adenovirus in children after allogeneic hematopoietic stem cell
      transplantation.
AB  - Adenovirus (ADV) can cause significant morbidity and mortality in children
      following haematopoietic stem cell transplantation (HSCT), with an incidence of
      up to 27% and notable associated morbidity and mortality. T-cell depleted grafts
      and severe lymphopenia are major risk factors for the development of adenovirus
      disease after HSCT. Current antiviral treatments are at best virostatic and may
      have significant side effects. Adoptive transfer of donor-derived virus-specific
      T cells has been shown to be an effective strategy for the prevention and
      treatment of ADV infection after HSCT. Here we review progress in the field and
      present a pathway for the management of adenovirus in the posttransplant setting.

PMID- 24288537
TI  - Prognostic significance of serum free light chains in chronic lymphocytic
      leukemia.
AB  - Background. Serum free light chains (sFLC), the most commonly detected
      paraprotein in CLL, were recently proposed as useful tools for the
      prognostication of CLL patients. Objective. To investigate the prognostic
      implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients'
      series. Patients and Methods. We studied 143 CLL patients of which 18 were
      symptomatic and needed treatment, while 37 became symptomatic during follow-up.
      Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively.
      Median patients' followup was 32 months (range 4-228). Results. Increased
      involved (restricted) sFLC (iFLC) was found in 42% of patients, while the
      summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC
      values as well as those of summated FLC above 60 were related to shorter time to
      treatment (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and
      P = 0.003, resp.). They also correlated with beta 2-microglobulin (P = 0.009 and
      P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P <
      0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and
      with the presence of beta symptoms (P = 0.004 for summated sFLC). Conclusion. We
      confirmed the prognostic significance of sFLC in CLL regarding both time to
      treatment and survival and showed their relationship with other parameters. 

PMID- 24288538
TI  - Acinetobacter baumannii: Role in Blood Stream Infection in Neonatal Unit, Dr.
      Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
AB  - Acinetobacter baumannii (A. baumannii) is Gram-negative coccobacilli that has
      emerged as a nosocomial pathogen. Several reports in Indonesia showed the
      continuous presence of A. baumannii. This study aimed to determine the incidence
      of A. baumannii bacteremia in neonates in the Neonatal Unit Dr. Cipto
      Mangunkusumo Hospital (RSCM), Jakarta, Indonesia, and assess its role in blood
      stream infection using antibiogram and genotyping by pulsed-field gel
      electrophoresis (PFGE). Subjects were neonates with clinical sepsis. Blood
      specimens from the neonates and samples of suspected environment within the
      Neonatal Unit were cultivated. Antimicrobial resistance profiles were classified
      for analysis purpose. A. baumannii isolates were genotyped by PFGE to determine
      their similarity. A total of 24 A. baumannii were isolated from 80 neonates and
      the environment during this period of study. Seven isolates from the neonates
      showed multiple antimicrobial resistance (MDR), and 82% (n = 17) of the
      environment isolates were also MDR. Antibiotype "d" seemed to be predominant
      (62.5%). PFGE analysis showed a very close genetic relationship between the
      patients and environment isolates (Dice coefficient 0.8-1.0). We concluded that a
      mode of transmission of environmental microbes to patients was present in the
      Neonatal Unit of RSCM and thus needed to be overcome. 

PMID- 24288539
TI  - Salmonella in liquid eggs and other foods in fukuoka prefecture, Japan.
AB  - The study aimed to evaluate the prevalence of Salmonella in retail and wholesale
      foods in Fukuoka Prefecture, Japan. A total of 2,021 samples collected between
      1999 and 2010 were tested using a culture method. Samples consisted of liquid
      eggs (n = 30), meat (beef and pork) (n = 781), offal (n = 69), processed meats (n
      = 2), seafood (n = 232), processed seafood (dried fish) (n = 76), vegetables (n =
      481), processed vegetables (n = 87), fruits (n = 167), and herbs (n = 96) from
      574 outlets and wholesale agents in 15 areas (five samples were undocumented
      regarding outlets). Overall, liquid egg showed significantly (P < 0.001) higher
      frequencies of Salmonella contamination (13.3%) than beef (1/423, 0.2%) and pork
      (3/235, 1.3%). Salmonella enterica subsp. enterica serovar Enteritidis, the most
      common serovar as a human pathogen, were isolated from two liquid egg samples. No
      Salmonella were isolated from seafood and vegetable-related samples including
      seed sprouts (n = 261). In conclusion, liquid egg is a significant Salmonella
      vehicle, showing a need to continue the vaccination of chickens to prevent S.
      Enteritidis contamination in Japanese eggs. Moreover, further study is needed to
      evaluate Salmonella contamination in seed sprouts with more sampling from
      retailers there. 

PMID- 24288540
TI  - Capability and limitations of recent diagnostic criteria for autoimmune
      pancreatitis.
AB  - Because a diagnostic serological marker is unavailable, autoimmune pancreatitis
      (AIP) is diagnosed based on unique features. The diagnostic capabilities and
      potential limitations of four sets of diagnostic criteria for AIP (Japanese
      diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international
      consensus diagnostic criteria (ICDC)) were compared among 85 patients who were
      diagnosed AIP according to at least one of the four sets. AIP was diagnosed in
      87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian,
      ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and
      2 AIP independently and show high sensitivity for diagnosis of AIP. However, as
      the ICDC are rather complex, diagnostic criteria for AIP should perhaps be
      revised and tailored to each country based on the ICDC. 

PMID- 24288541
TI  - The utility of outcome measures in total knee replacement surgery.
AB  - Total knee replacement (TKR) is the mainstay of treatment for people with end
      stage knee OA among suitably "fit" candidates. As a high cost, high volume
      procedure with a worldwide demand that continues to grow it has become
      increasingly popular to measure response to surgery. While the majority who
      undergo TKR report improvements in pain and function following surgery, a
      significant proportion of patients report dissatisfaction with surgery as a
      result of ongoing pain or poor function. Poor outcomes of TKR require care that
      imposes on already overburdened health systems. Accurate and meaningful capture
      and interpretation of outcome data are imperative for appropriate patient
      selection, informing those at risk, and for developing strategies to mitigate the
      risk of poor results and dissatisfaction. The ways in which TKR outcomes are
      captured and analysed, the level of follow-up, the types of outcome measures
      used, and the timing of their application vary considerably within the
      literature. With this in mind, we reviewed four of the most commonly used joint
      specific outcome measures in TKR. We report on the utility, strengths, and
      limitations of the Oxford knee score (OKS), knee injury and osteoarthritis
      outcome score (KOOS), Western Ontario and McMaster Universities osteoarthritis
      index (WOMAC), and knee society clinical rating system (KSS). 

PMID- 24288542
TI  - Obesity and the Endometrium: Adipocyte-Secreted Proinflammatory TNF alpha
      Cytokine Enhances the Proliferation of Human Endometrial Glandular Cells.
AB  - Obesity, a state of chronic inflammation, is associated with poor fertility and
      low implantation rates and is a well-documented risk factor for endometrial
      cancer. Adipokines, such as tumor necrosis factor alpha, play an important role
      in initiation of endometrial cancer. The aim of this study is to evaluate in
      vitro effects of human adipocyte cells (SW872) on growth of endometrial glandular
      epithelial cells (EGE). Methods. We measured cell proliferation and expression of
      cell-growth proteins-proliferating cell nuclear antigen, cyclin D1, cyclin
      dependent kinase-1, and apoptotic markers (BCL-2 and BAK) in human EGE cells
      cocultured with SW872 cells. EGE cells were also evaluated in SW872-conditioned
      media neutralized with anti-TNF alpha antibody. Results. A significant increase
      in EGE cell proliferation was observed in both SW872-conditioned media and in
      coculture (P < 0.05). We observed an upregulation of proliferation markers PCNA,
      cyclin D1, CDK-1, and BCL-2 and decrease in BAK (P < 0.05). Neutralization of
      SW872-conditioned media using anti-TNF alpha antibodies reversed EGE cell
      proliferation as indicated by BCL-2 expression. Conclusions. Adipocytes have
      potent proliferative paracrine effect on EGE cells which may be, in part,
      mediated via TNF alpha . Further understanding of the role of obesity in
      endometrial carcinogenesis should lead to better preventative and therapeutic
      strategies. 

PMID- 24288543
TI  - The Effect of Ethnicity on 2D and 3D Frontomaxillary Facial Angle Measurement in
      the First Trimester.
AB  - Objectives. To determine the existence and extent of ethnic differences in 2D or
      3D fetal frontomaxillary facial angle (FMFA) measurements. Methods. During
      routine 11-14 weeks nuchal translucency screening undertaken in a private
      ultrasound practice in Sydney, Australia, 2D images and 3D volumes of the fetal
      profile were collected from consenting patients. FMFA was measured on a frozen 2D
      ultrasound image in the appropriate plane and, after a delay of at least 48
      hours, was also measured on the reconstructed 3D ultrasound volume offline.
      Results. Overall 416 patients were included in the study; 220 Caucasian, 108
      north Asian, 36 east Asian and 52 south Asian patients. Caucasians had
      significantly lower median FMFA measurements than Asians in both 2D (2.2 degrees
      ; P < 0.001) and 3D (3.4 degrees ; P < 0.001) images. Median 2D measurements were
      significantly higher than 3D measurements in the Caucasian and south Asian groups
      (P < 0.001 and P = 0.04), but not in north and east Asian groups (P = 0.08 and P
      = 0.41). Conclusions. Significant ethnic variations in both 2D and 3D FMFA
      measurements exist. These differences may indicate the need to establish ethnic
      specific reference ranges for both 2D and 3D imaging. 

PMID- 24288544
TI  - A rare case presentation of a perforated giant sigmoid diverticulum.
AB  - Giant sigmoid diverticulum (GSD) is a rare complication of diverticulosis. These
      lesions arise from herniations of the mucosa through the muscle wall which
      progressively enlarge with colonic gas to become large air-filled cysts evident
      on plain X-ray and CT scans. We present a rare case of a 72-year-old female
      presenting with abdominal distention, abdominal tenderness, and fever who
      developed a type 1 giant sigmoid diverticulum (pseudodiverticulum) that
      subsequently formed an intra-abdominal abscess and an accompanying type 2
      diverticulum as well. The patient was treated with surgical resection of the
      diverticulum with a primary anastomosis and abscess drainage. The patient's
      postoperative course was uneventful. This case helps to support the need for the
      consideration of GSD in patients aged 60 and older with a history of
      diverticulosis and presenting with abdominal discomfort and distension. 

PMID- 24288545
TI  - DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem
      Cells: Implications for Their Genomic Stability?
AB  - Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous
      diseases. A major problem for MSC therapeutic use is represented by the very low
      amount of MSCs which can be isolated from different tissues; thus ex vivo
      expansion is indispensable. Long-term culture, however, is associated with
      extensive morphological and functional changes of MSCs. In addition, the concern
      that they may accumulate stochastic mutations which lead the risk of malignant
      transformation still remains. Overall, the genome of human MSCs (hMSCs) appears
      to be apparently stable throughout culture, though transient clonal aneuploidies
      have been detected. Particular attention should be given to the use of low-oxygen
      environment in order to increase the proliferative capacity of hMSCs, since data
      on the effect of hypoxic culture conditions on genomic stability are few and
      contradictory. Furthermore, specific and reproducible epigenetic changes were
      acquired by hMSCs during ex vivo expansion, which may be connected and trigger
      all the biological changes observed. In this review we address current issues on
      long-term culture of hMSCs with a 360-degree view, starting from the genomic
      profiles and back, looking for an epigenetic interpretation of their genetic
      stability. 

PMID- 24288546
TI  - Adiponectin deficiency blunts hypoxia-induced mobilization and homing of
      circulating angiogenic cells.
AB  - Aim. We investigated the effects of adiponectin deficiency on circulating
      angiogenic cell (CAC) mobilization, homing, and neovascularization in the setting
      of acute myocardial infarction (AMI). Methods & Results. AMI was induced in wild
      type (WT) (n = 10) and adiponectin knockout (Adipoq (-/-)) mice (n = 7). One week
      after AMI, bone marrow (BM) concentration and mobilization of Sca-1(+) and Lin(
      )Sca-1(+) progenitor cells (PCs) were markedly attenuated under Adipoq (-/-)
      conditions, as assessed by flow cytometry. The mRNA expression of HIF-1-dependent
      chemotactic factors, such as Cxcl12 (P = 0.005) and Ccl5 (P = 0.025), and
      vascular adhesion molecules, such as Icam1 (P = 0.010), and Vcam1 (P = 0.014),
      was significantly lower in the infarction border zone of Adipoq (-/-) mice.
      Histologically, Adipoq (-/-) mice evidenced a decrease in neovascularization
      capacity in the infarction border zone (P < 0.001). Overall, capillary density
      was positively correlated with Sca-1(+) PC numbers in BM (P = 0.01) and
      peripheral blood (PB) (P = 0.005) and with the expression of the homing factors
      Cxcl12 (P = 0.013), Icam1 (P = 0.034) and Vcam1 (P = 0.014). Conclusions.
      Adiponectin deficiency reduced the BM reserve and mobilization capacity of CACs,
      attenuated the expression of hypoxia-induced chemokines and vascular adhesion
      molecules, and impaired the neovascularization capacity one week after AMI. 

PMID- 24288547
TI  - Kidney and urinary tract involvement in kawasaki disease.
AB  - Kawasaki disease (KD) is a systemic vasculitis and can develop multiple organ
      injuries including kidney and urinary tract involvement. These disorders include
      pyuria, prerenal acute kidney injury (AKI), renal AKI caused by
      tubulointerstitial nephritis (TIN), hemolytic uremic syndrome (HUS), and immune
      complex mediated nephropathy, renal AKI associated with either Kawasaki disease
      shock syndrome or unknown causes, acute nephritic syndrome (ANS), nephrotic
      syndrome (NS), renal tubular abnormalities, renal abnormalities in imaging
      studies, and renal artery lesions (aneurysms and stenosis). Pyuria is common in
      KD and originates from the urethra and/or the kidney. TIN with AKI and renal
      tubular abnormalities probably result from renal parenchymal inflammation caused
      by T-cell activation. HUS and renal artery lesions are caused by vascular
      endothelial injuries resulting from vasculitis. Some patients with ANS have
      immunological abnormalities associated with immune-complex formation.
      Nephromegaly and renal parenchymal inflammatory foci are detected frequently in
      patients with KD by renal ultrasonography and renal scintigraphy, respectively.
      Although the precise pathogenesis of KD is not completely understood, renal
      vasculitis, immune-complex mediated kidney injuries, or T-cell immune-regulatory
      abnormalities have been proposed as possible mechanisms for the development of
      kidney and urinary tract injuries. 

PMID- 24288548
TI  - Total chemical synthesis of a heterodimeric interchain bis-lactam-linked Peptide:
      application to an analogue of human insulin-like Peptide 3.
AB  - Nonreducible cystine isosteres represent important peptide design elements in
      that they can maintain a near-native tertiary conformation of the peptide while
      simultaneously extending the in vitro and in vivo half-life of the biomolecule.
      Examples of these cystine mimics include dicarba, diselenide, thioether,
      triazole, and lactam bridges. Each has unique physicochemical properties that
      impact upon the resulting peptide conformation. Each also requires specific
      conditions for its formation via chemical peptide synthesis protocols. While the
      preparation of peptides containing two lactam bonds within a peptide is
      technically possible and reported by others, to date there has been no report of
      the chemical synthesis of a heterodimeric peptide linked by two lactam bonds. To
      examine the feasibility of such an assembly, judicious use of a complementary
      combination of amine and acid protecting groups together with nonfragment-based,
      total stepwise solid phase peptide synthesis led to the successful preparation of
      an analogue of the model peptide, insulin-like peptide 3 (INSL3), in which both
      of the interchain disulfide bonds were replaced with a lactam bond. An analogue
      containing a single disulfide-substituted interchain lactam bond was also
      prepared. Both INSL3 analogues retained significant cognate RXFP2 receptor
      binding affinity. 

PMID- 24288550
TI  - Pollutants source control and health effects.

PMID- 24288549
TI  - Adiponectin, Leptin, and Resistin in Asthma: Basic Mechanisms through Population
      Studies.
AB  - Adipokines, factors produced by adipose tissue, may be proinflammatory (such as
      leptin and resistin) or anti-inflammatory (such as adiponectin). Effects of these
      adipokines on the lungs have the potential to evoke or exacerbate asthma. This
      review summarizes basic mechanistic data through population-based and clinical
      studies addressing the potential role of adipokines in asthma. Augmenting
      circulating concentrations of adiponectin attenuates allergic airway inflammation
      and airway hyperresponsiveness in mice. Murine data is supported by human data
      that suggest that low serum adiponectin is associated with greater risk for
      asthma among women and peripubertal girls. Further, higher serum total
      adiponectin may be associated with lower clinical asthma severity among children
      and women with asthma. In contrast, exogenous administration of leptin results in
      augmented allergic airway hyperresponsiveness in mice. Alveolar macrophages
      obtained from obese asthmatics are uniquely sensitive to leptin in terms of their
      potential to augment inflammation. Consistent with this basic mechanistic data,
      epidemiologic studies demonstrate that higher serum leptin is associated with
      greater asthma prevalence and/or severity and that these associations may be
      stronger among women, postpubertal girls, and prepubertal boys. The role of
      adipokines in asthma is still evolving, and it is not currently known whether
      modulation of adipokines may be helpful in asthma prevention or treatment. 

PMID- 24288551
TI  - Correlation between the frequency of Th17 cell and the expression of microRNA-206
      in patients with dermatomyositis.
AB  - It was reported that IL-17 had been detected in the inflammatory infiltrates of
      patients with DM (dermatomyositis). In this study, we investigated the frequency
      of Th17 cells and the expression of microRNA-206 (miR-206) in DM patients.
      Firstly, we observed that the frequency of Th17 cells and the expression of
      transcription factors were increased significantly in the PBMCs of DM patients.
      Secondly, we found that there was a positive correlation between the percentages
      of Th17 cells and serum level of CK in DM patients. And the serum concentrations
      of IL-6, IL-1beta, TGF-beta, and IL-23, the important cytokines of Th17
      differentiation, were increased in DM patients. It was predicted that Kruppel
      like factor 4 (KLF4) is one of the multiple targets of miR-206. We detected the
      expression of miR-206 in DM patients, and it was decreased in the serum and PBMCs
      of DM patients. The augmented expression of KLF is accompanied by the attenuated
      expression of miR-206. Furthermore, a negative correlation between the
      percentages of Th17 cells and the expression of miR-206 in DM patients has been
      found. Taken together, these findings suggest the attenuated expression of miR
      206, and the augmented frequency of Th17 cells in DM patients.

PMID- 24288552
TI  - Induction of Th17 lymphocytes and Treg cells by monocyte-derived dendritic cells
      in patients with rheumatoid arthritis and systemic lupus erythematosus.
AB  - Dendritic cells (DCs) have a key role in the regulation of immune response. We
      herein explored, in patients with inflammatory diseases, the role of monocyte
      derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg)
      lymphocytes. Peripheral blood was obtained from thirty-five patients with
      rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and
      twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or
      tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10)
      conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We
      detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and
      IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs
      from SLE patients also released high levels of IL-6/IL-23, it did not show an
      increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients
      with RA and SLE generated under the engagement of PSGL-1, showed a defective
      capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE,
      when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs
      from patients with rheumatic inflammatory disease show an aberrant function that
      may have an important role in the pathogenesis of these conditions. 

PMID- 24288553
TI  - Overexpression of HIF-2alpha, TWIST, and CXCR4 is associated with lymph node
      metastasis in papillary thyroid carcinoma.
AB  - This study aimed to examine HIF-2alpha, TWIST, and CXCR4 expression in papillary
      thyroid carcinoma (PTC) and assesses the association of their expression with
      clinicopathological indicators. HIF-2alpha, TWIST, and CXCR4 protein expression
      in 129 PTCs, 61 nodular hyperplasia, and 118 normal thyroid tissue specimens was
      analyzed using immunohistochemistry. The protein expression levels of these three
      molecules were upregulated in PTCs. High protein expression of HIF-2alpha, TWIST,
      and CXCR4 was significantly correlated with lymph node metastasis (LNM) (P <
      0.001). Furthermore, HIF-2alpha, TWIST, and CXCR4 protein expression was
      correlated with one another. Concomitant high expression of these molecules had
      stronger correlation with LNM than did each alone (P = 0.032 for HIF
      2alpha/TWIST, P < 0.001 for HIF-2alpha/CXCR4, P = 0.018 for TWIST/CXCR4, and P <
      0.001 for HIF-2alpha/TWIST/CXCR4). Additionally, HIF-2alpha, TWIST, and CXCR4
      mRNA expression were assessed in 30 PTCs, 10 nodular hyperplasia, and 10 normal
      thyroid tissue specimens using real-time RT-PCR. TWIST and CXCR4 mRNA expression
      levels were up-regulated in PTCs, and high mRNA expression of TWIST and CXCR4 was
      significantly correlated with LNM (P = 0.005 and P = 0.010, resp.). These results
      demonstrated that the evaluation of HIF-2alpha, TWIST, and CXCR4 expression in
      PTC may be useful in predicting the risk of LNM.

PMID- 24288554
TI  - CD8 knockout mice are protected from challenge by vaccination with WR201, a live
      attenuated mutant of Brucella melitensis.
AB  - CD8+ T cells have been reported to play an important role in defense against B.
      abortus infection in mouse models. In the present report, we use CD8 knockout
      mice to further elucidate the role of these cells in protection from B.
      melitensis infection. Mice were immunized orally by administration of B.
      melitensis WR201, a purine auxotrophic attenuated vaccine strain, then challenged
      intranasally with B. melitensis 16M. In some experiments, persistence of WR201 in
      the spleens of CD8 knockout mice was slightly longer than that in the spleens of
      normal mice. However, development of anti-LPS serum antibody, antigen-induced
      production of gamma-interferon (IFN-gamma) by immune splenic lymphocytes,
      protection against intranasal challenge, and recovery of nonimmunized animals
      from intranasal challenge were similar between normal and knockout animals.
      Further, primary Brucella infection was not exacerbated in perforin knockout and
      Fas-deficient mice and these animals' anti-Brucella immune responses were
      indistinguishable from those of normal mice. These results indicate that CD8+ T
      cells do not play an essential role as either cytotoxic cells or IFN-gamma
      producers, yet they do participate in a specific immune response to immunization
      and challenge in this murine model of B. melitensis infection.

PMID- 24288556
TI  - Standardized versus Individualized Acupuncture for Chronic Low Back Pain: A
      Randomized Controlled Trial.
AB  - We aimed to compare the effectiveness of standardized and individualized
      acupuncture treatment in patients with chronic low back pain. A single-center
      randomized controlled single-blind trial was performed in a general medical
      practice in Germany run by a Chinese-born medical doctor trained in western and
      Chinese medicine. One hundred and fifty outpatients with chronic low back pain
      were randomly allocated to two groups (78 standardized and 72 individualized
      acupuncture). Patients received either standardized acupuncture or individualized
      acupuncture. Treatment encompassed between 10 and 15 treatments based on
      individual symptoms with two treatments per week. The main outcome measure was
      the area under the curve (AUC) summarizing eight weeks of daily rated pain
      severity measured with a visual analogue scale (0 mm = no pain, 100 mm = worst
      imaginable pain). No significant differences between groups were observed for the
      AUC (individualized acupuncture mean: 1768.7 (95% CI, 1460.4; 2077.1);
      standardized acupuncture 1482.9 (1177.2; 1788.7); group difference, 285.8 (-33.9;
      605.5) P = 0.080). In this single-center trial, individualized acupuncture was
      not superior to standardized acupuncture for patients suffering from chronic
      pain. As a next step, a multicenter noninferiority study should be performed to
      investigate whether standardised acupuncture treatment for chronic low back pain
      might be applicable in a broader usual care setting. This trial is registered
      with ClinicalTrials.gov NCT00758017. 

PMID- 24288555
TI  - BCG and BCG/DNAhsp65 vaccinations promote protective effects without deleterious
      consequences for experimental autoimmune encephalomyelitis.
AB  - A prime-boost strategy conserving BCG is considered the most promising vaccine to
      control tuberculosis. A boost with a DNA vaccine containing the mycobacterial
      gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against
      experimental tuberculosis. However, anti-hsp65 immunity could worsen an
      autoimmune disease due to molecular mimicry. In this investigation, we evaluated
      the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental
      autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized
      with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE
      induction and were daily evaluated for weight loss and clinical score. They were
      euthanized during recovery phase to assess immune response and inflammatory
      infiltration at the central nervous system. Previous immunization did not
      aggravate or accelerate clinical score or weight loss. In addition, this
      procedure clearly decreased inflammation in the brain. BCG immunization modulated
      the host immune response by triggering a significant reduction in IL-10 and IFN
      gamma levels induced by myelin basic protein. These data indicated that
      vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not
      trigger a deleterious effect on EAE evolution.

PMID- 24288557
TI  - Spiritually and religiously integrated group psychotherapy: a systematic
      literature review.
AB  - WE SYSTEMATICALLY REVIEWED THE RESEARCH LITERATURE ON SPIRITUALLY AND RELIGIOUSLY
      INTEGRATED GROUP PSYCHOTHERAPY TO ANSWER THE FOLLOWING THREE QUESTIONS: first,
      how are spirituality and religiosity defined; second, how are spiritual and
      religious factors characterized and integrated into group psychotherapy; and,
      third, what is the outcome of the group psychotherapies? We searched in two
      databases: PsycINFO and PubMed. Inclusion and exclusion criteria and checklists
      from standardized assessment tools were applied to the research literature.
      Qualitative and quantitative papers were included. In total, 8 articles were
      considered eligible for the review. Findings from the evaluation suggested that
      the concepts of spirituality and religiosity were poorly conceptualized and the
      way in which spiritual and religious factors were integrated into such group
      psychotherapies, which distinguished it from other types of group
      psychotherapies, was not fully conceptualized or understood either. However,
      clear and delimited conceptualization of spiritual and religious factors is
      crucial in order to be able to conclude the direct influences of spiritual or
      religious factors on outcomes. Implications for spiritually or religiously
      integrated group psychotherapy and conducting research in this field are
      propounded. 

PMID- 24288558
TI  - Ethanol Extract of Lepidium apetalum Seed Elicits Contractile Response and
      Attenuates Atrial Natriuretic Peptide Secretion in Beating Rabbit Atria.
AB  - The seeds of Lepidium apetalum Willdenow (called "Tinglizi" in China and
      "Jungryukza" in Korea) have been used to discharge phlegm and improve dropsy in
      Oriental medicine. The present study investigated the effects of ethanol extract
      of the seeds of Lepidium apetalum (ELA) on atrial dynamics and atrial natriuretic
      peptide (ANP) secretion in beating rabbit atria. ELA increased atrial stroke
      volume, pulse pressure, and cAMP efflux, concomitantly attenuating ANP secretion
      in a dose-dependent manner. ELA-induced increases in atrial stroke volume, pulse
      pressure, and cAMP levels and decrease in ANP secretion were not inhibited by
      pretreatment with staurosporine, a nonspecific protein kinase inhibitor, or
      diltiazem and verapamil, the L-type Ca(2+) channel blockers, respectively.
      Helveticoside, a well-known digitalis-like cardiac glycosidic constituent of ELA,
      also increased atrial dynamics, including stroke volume and pulse pressure,
      without changing cAMP efflux and ANP secretion, and the effects of helveticoside
      were not inhibited by pretreatment with staurosporine, diltiazem, and verapamil.
      These results suggest that the ELA-induced positive inotropic activity in beating
      rabbit atria might, at least partly, be due to the digitalis-like activity of
      helveticoside rather than an increase in cAMP efflux. 

PMID- 24288559
TI  - Inhibition of Acute Phase Inflammation by Laminaria japonica through Regulation
      of iNOS-NF- kappa B Pathway.
AB  - Laminaria japonica has been frequently used as food supplements in many of the
      Asian countries and as a drug in traditional oriental medicine. This research
      investigated the effects of Laminaria japonica extract (LJE) on acute phase
      inflammation in a carrageenan-induced paw edema model, as assessed by
      histomorphometric and immunohistochemical analyses. The effect of LJE was also
      evaluated in Raw264.7 cells stimulated with lipopolysaccharide (LPS) in the
      aspect of the inhibition of nitric oxide (NO), prostaglandin E2 (PGE2), and
      proinflammatory cytokines production. NO, PGE2, tumor necrosis factor (TNF)-
      alpha , interleukin-1 beta , and interleukin-6 contents were assayed by ELISA,
      and inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expressions were
      determined by western blot analyses. In rats, LJE treatment inhibited carrageenan
      induced paw edema formation and infiltration of inflammatory cells in H&E
      staining. LJE treatment prevented the ability of LPS to increase the levels of
      iNOS and COX-2 protein in a concentration-dependent manner. Consistently, LJE
      suppressed the production of TNF- alpha , interleukin-1 beta , and interleukin-6.
      Treatment of the cells with LJE caused inhibition of inhibitor of kappa B alpha
      phosphorylation induced by LPS, suggesting LJE repression of nuclear factor-
      kappa B activity by LPS. In conclusion, this study shown here may be of help to
      understand the action mechanism of LJE and the anti-inflammatory use of L.
      japonica. 

PMID- 24288560
TI  - Relationships between Pathological Patterns and Quality of Life: Pathway
      Analysis.
AB  - Purpose. The purpose of our study was to examine the relationships between
      pathological patterns and self-rated quality of life (QoL). Methods. A total of
      426 Korean subjects participated in this study (male : female = 154 : 272). The
      subjects were asked to complete Yin Deficiency (YD), Qi Deficiency (QD), Food
      Stagnation (FS), Blood Stasis (BS), Phlegm, and Seven Emotions Impairment (SEI)
      pattern Questionnaires and the General Health Questionnaire (GHQ). We formed a
      pathway model consisting of pathological patterns and QoL questionnaire scores
      and examined which pathological patterns resulted in decreased QoL using path
      analysis. Results. Our pathway model had satisfactory fitness levels (GFI =
      0.975, NFI = 0.984, and CFI = 0.984) and showed that Phlegm and SEI patterns
      directly resulted in decreased QoL, whereas QD, YD, FD, and BS indirectly
      resulted in decreased QoL. The pathway model suggested that the severity or stage
      of decreased QoL may be estimated by pathological patterns: QD and YD patterns
      are associated with the early stage; FS and BS patterns are associated with the
      middle stage; Phlegm and SEI are associated with the later stage of decreased
      QoL. Conclusion. Our results suggest that pathological patterns directly or
      indirectly affect decreases in QoL. 

PMID- 24288561
TI  - Rubi Fructus (Rubus coreanus) Inhibits Differentiation to Adipocytes in 3T3-L1
      Cells.
AB  - Rubi Fructus (RF) is known to exert several pharmacological effects including
      antitumor, antioxidant, and anti-inflammatory activities. However, its
      antiobesity effect has not been reported yet. This study was focused on the
      antidifferentiation effect of RF extract on 3T3-L1 preadipocytes. When 3T3-L1
      preadipocytes were differentiating into adipocytes, 10-100  MU g/mL of RF was
      added. Next, the lipid contents were quantified by Oil Red O staining. RF
      significantly reduced lipid accumulation and downregulated the expression of
      peroxisome proliferator-activated receptor gamma (PPAR gamma ), CCAAT0-enhancer
      binding proteins alpha (C/EBP alpha ), adipocyte fatty acid-binding protein 2
      (aP2), resistin, and adiponectin in ways that were concentration dependent.
      Moreover, RF markedly upregulated liver kinase B1 and AMP-activated protein
      kinase (AMPK). Interestingly, pretreatment with AMPK alpha siRNA and RF
      downregulated the expression of PPAR gamma and C/EBP alpha protein as well as the
      adipocyte differentiation. Our study shows that RF is capable of inhibiting the
      differentiation of 3T3-L1 adipocytes through the modulation of PPAR gamma , C/EBP
      alpha , and AMPK, suggesting that it has a potential for therapeutic application
      in the treatment or prevention of obesity. 

PMID- 24288562
TI  - Effect of low-level laser stimulation on EEG power in normal subjects with closed
      eyes.
AB  - In a previous study, we found that the low-level laser (LLL) stimulation at the
      palm with a frequency of 10 Hz was able to induce significant brain activation in
      normal subjects with opened eyes. However, the electroencephalography (EEG)
      changes to LLL stimulation in subjects with closed eyes have not been studied. In
      the present study, the laser array stimulator was applied to deliver insensible
      laser stimulations to the palm of the tested subjects with closed eyes (the laser
      group). The EEG activities before, during, and after the laser stimulation were
      collected. The EEG amplitude powers of each EEG frequency band at 19 locations
      were calculated. These power data were then analyzed by SPSS software using
      repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced
      decrease in the EEG power in alpha-bandwidth during laser simulation and then
      less decrease in the EEG power in delta-bandwidth in normal subjects with laser
      stimulation. The EEG power in beta-bandwidth in the right occipital area also
      decreased significantly in the laser group. We suggest that LLL stimulation might
      be conducive to falling into sleep in patients with sleep problems. 

PMID- 24288563
TI  - Investigation into the influence of physician for treatment based on syndrome
      differentiation.
AB  - Background. The characteristics of treatment based on syndrome differentiation
      (TBSD) cause great challenges to evaluate the effectiveness of the clinical
      methods. Objectives. This paper aims to evaluate the influence of physician to
      personalized medicine in the process of TBSD. Methods. We performed a randomized,
      triple-blind trial involving patients of primary insomnia treated by 3 physicians
      individually and independently. The patients (n = 30) were randomly assigned to
      receive treatments by the 3 physicians for every visit. However, they always
      received the treatment, respectively, prescribed by the physician at the first
      visit. The primary outcome was evaluated, respectively, by the Pittsburgh Sleep
      Quality Index (PSQI) and the TCM symptoms measuring scale. The clinical practices
      of the physicians were recorded at every visit including diagnostic information,
      syndrome differentiation, treating principles, and prescriptions. Results. All
      patients in the 3 groups (30 patients) showed significant improvements (>66%)
      according to the PSQI and TCM symptoms measuring scale. Conclusion. The results
      indicate that although with comparable effectiveness, there exist significant
      differences in syndrome differentiation, the treating principles, and the
      prescriptions of the approaches used by the 3 physicians. This means that the
      physician should be considered as an important factor for individualized medicine
      and the related TCM clinical research. 

PMID- 24288564
TI  - A systematic review and meta-analysis of qigong for the fibromyalgia syndrome.
AB  - Objectives. The fibromyalgia syndrome (FMS) is a chronic condition with only few
      evidence-based complementary and alternative therapies available. This paper
      presents a systematic review and meta-analysis of the effectiveness of Qigong for
      fibromyalgia syndrome. Methods. The PubMed/MEDLINE, Cochrane Library, Embase,
      PsycINFO, and Cambase databases were screened in December 2012 to identify
      randomized controlled trials comparing Qigong to control interventions. Major
      outcome measures were pain and quality of life; and secondary outcomes included
      sleep quality, fatigue, depression, and safety. Standardized mean differences
      (SMD) and 95% confidence intervals were calculated. Results. Seven trials were
      located with a total of 395 FMS patients. Analyses revealed low quality evidence
      for short-term improvement of pain, quality of life, and sleep quality and very
      low quality evidence for improvement of fatigue after Qigong for FMS, when
      compared to usual care. No evidence was found for superiority of Qigong compared
      to active treatments. No serious adverse events were reported. Discussion. This
      systematic review found that Qigong may be a useful approach for FMS patients.
      According to the quality of evidence, only a weak recommendation for Qigong can
      be made at this point. Further high quality RCTs are required for the conclusive
      judgment of its long-term effects. 

PMID- 24288565
TI  - Secular, Spiritual, and Religious Existential Concerns of Women with Ovarian
      Cancer during Final Diagnostics and Start of Treatment.
AB  - Introduction. This paper deals with secular, spiritual, and religious existential
      concerns during severe illness. Materials and Methods. Qualitative research
      interviews were made before and after surgery with women who underwent final
      diagnostics, surgery, and chemotherapy for ovarian cancer. By applying a
      phenomenological-hermeneutic text interpretation methodology the findings were
      systematically identified, placed into meaning structures, interpreted, and
      critically discussed. Results. The analysis offered insight into the complexity
      of challenges and personal development over time in being a woman with ovarian
      cancer during her first treatment period. Although the women experienced their
      health to be seriously threatened, they also felt hope, will, and courage. The
      diagnostic procedures and treatment had comprehensive impact on their lives.
      However, hope and spirituality were important resources of comfort and meaning.
      Conclusion. Hope and courage to face life represent significant personal
      resources that are created not only in the interplay between body and mind but
      also between patients and their healthcare professionals. The women dealt with
      this in a dialectical manner, so that hope and despair could be present
      simultaneously. In this process secular, spiritual, and religious existential
      meaning orientations assisted the women in creating new narratives and obtain new
      orientations in life. 

PMID- 24288566
TI  - Subtoxic Levels of Apigenin Inhibit Expression and Secretion of VEGF by Uveal
      Melanoma Cells via Suppression of ERK1/2 and PI3K/Akt Pathways.
AB  - The effects of apigenin on the expression of VEGF in uveal melanoma cells have
      not been reported. We studied this effect and relevant signaling pathways in two
      human uveal melanoma cell lines (SP6.5 and C918). ELISA assay revealed that the
      constitutive secretion of VEGF by uveal melanoma cells was 21-fold higher than
      that in normal uveal melanocytes. Apigenin at subtoxic levels (1-5  MU M)
      significantly suppressed the secretion of VEGF in a dose- and time-dependent
      manner in melanoma cells. VEGF levels in the conditioned culture media from SP6.5
      and C918 cell lines treated with 5  MU M apigenin for 24 h reduced to 29% and 21%
      of those in cells not treated with apigenin, respectively. RT-PCR analysis found
      that apigenin also decreased the expression of VEGF mRNA in melanoma cells. ELISA
      study of various signal pathways showed that apigenin significantly decreased
      phosphorylated Akt and ERK1/2 but increased phosphorylated JNK1/2 and p38 MAPK
      levels in melanoma cells. PI3K/Akt or ERK1/2 inhibitors significantly decreased,
      but JNK1/2 and p38 MAPK inhibitors did not influence the secretion of VEGF by
      melanoma cells, suggesting that apigenin suppresses the secretion of VEGF mainly
      through the inhibition of PI3K/Akt and ERK1/2 pathways. 

PMID- 24288568
TI  - The Medicinal Values of Culinary-Medicinal Royal Sun Mushroom (Agaricus blazei
      Murrill).
AB  - Agaricus blazei Murrill (ABM), a mushroom native to Brazil, is a basidiomycete
      brown fungus, which is popularly known as "Cogumelo do Sol" in Brazil or
      "Himematsutake" in Japan, and there has been a prominent increase in the use of
      ABM for therapeutic and medicinal purposes. ABM is useful against a variety of
      diseases like cancer, tumor, chronic hepatitis, diabetes, atherosclerosis,
      hypercholesterolemia, and so on. In this review, we demonstrated various
      pharmacological effects of ABM, so that we can use different effects of ABM
      against different diseases and provide reference for the study of ABM in the
      future. 

PMID- 24288569
TI  - Network-based biomarkers for cold coagulation blood stasis syndrome and the
      therapeutic effects of shaofu zhuyu decoction in rats.
AB  - In this study, the reverse docking methodology was applied to predict the action
      targets and pathways of Shaofu Zhuyu decoction (SFZYD) bioactive ingredients.
      Furthermore, Traditional Chinese Medicine (TCM) cold coagulation blood stasis
      (CCBS) syndrome was induced in female Sprague-Dawley rats with an ice-water bath
      and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic
      approach was used to evaluate changes in the metabolic profiles and to analyze
      the pharmacological mechanism of SFZYD actions. Twenty-three potential protein
      targets and 15 pathways were discovered, respectively; among these, pathways are
      associated with inflammation and immunological stress, hormone metabolism,
      coagulation function, and glycometabolism. There were also changes in the levels
      of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous
      metabolites were identified. Furthermore, the relative quantities of 6 endogenous
      metabolites in the plasma and 5 in the urine were significantly affected by SFZYD
      (P < 0.05). The pharmacological mechanism of SFZYD was partially associated with
      glycerophospholipid metabolism and pentose and glucuronate interconversions. In
      conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water
      and epinephrine was complex and related to multiple metabolic pathways. SFZYD did
      regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used
      for the clinical treatment of CCBS syndrome. 

PMID- 24288570
TI  - Diet and nutrition in cancer survivorship and palliative care.
AB  - The primary goal of palliative cancer care is typically to relieve suffering and
      improve quality of life. Most approaches to diet in this setting have focused
      only on eating as many calories as possible to avoid cachexia. However, as the
      concept of palliative care has evolved to include all aspects of cancer
      survivorship and not just end of life care, there is an increasing need to
      thoughtfully consider diet and nutrition approaches that can impact not only
      quality of life but overall health outcomes and perhaps even positively affect
      cancer recurrence and progression. In this regard, there has been a recent
      emphasis in the literature on nutrition and cancer as an important factor in both
      quality of life and in the pathophysiology of cancer. Hence, the primary purpose
      of this paper is to review the current data on diet and nutrition as it pertains
      to a wide range of cancer patients in the palliative care setting. 

PMID- 24288572
TI  - Traditional chinese medicine tang-luo-ning ameliorates sciatic nerve injuries in
      streptozotocin-induced diabetic rats.
AB  - Diabetic peripheral neuropathy (DPN) is a common microvascular complication of
      diabetes associated with high disability rate and low quality of life. Tang-Luo
      Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN.
      To illustrate the underlying neural protection mechanisms of TLN, the effect of
      TLN on electrophysiology and sciatic nerve morphology was investigated in a model
      of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor
      nerve conduction velocity and digital sensory nerve conduction velocity were
      reduced in DPN and were significantly improved by TLN or alpha -lipoic acid at 10
      and 20 weeks after streptozotocin injection. It was demonstrated that TLN
      intervention for 20 weeks significantly alleviated pathological injury as well as
      increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA
      expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and
      mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel
      therapeutic properties of TLN to promote Schwann cell survival may offer a
      promising alternative medicine for the patients to delay the progression of DPN.
      The underlying mechanism may be that TLN exerts neural protection effect after
      sciatic nerve injury through Nrg1/ErbB2->Erk/Bad Schwann cell survival signaling
      pathway. 

PMID- 24288571
TI  - Effects and mechanisms of chinese herbal medicine in ameliorating myocardial
      ischemia-reperfusion injury.
AB  - Myocardial ischemia-reperfusion (MIR) injury is a major contributor to the
      morbidity and mortality associated with coronary artery disease, which accounts
      for approximately 450,000 deaths a year in the United States alone. Chinese
      herbal medicine, especially combined herbal formulations, has been widely used in
      traditional Chinese medicine for the treatment of myocardial infarction for
      hundreds of years. While the efficacy of Chinese herbal medicine is well
      documented, the underlying molecular mechanisms remain elusive. In this review,
      we highlight recent studies which are focused on elucidating the cellular and
      molecular mechanisms using extracted compounds, single herbs, or herbal
      formulations in experimental settings. These studies represent recent efforts to
      bridge the gap between the enigma of ancient Chinese herbal medicine and the
      concepts of modern cell and molecular biology in the treatment of myocardial
      infarction. 

PMID- 24288573
TI  - The application of computer musculoskeletal modeling and simulation to
      investigate compressive tibiofemoral force and muscle functions in obese
      children.
AB  - This study aimed to utilize musculoskeletal modelling and simulation to
      investigate the compressive tibiofemoral force and individual muscle function in
      obese children. We generated a 3D muscle-driven simulation of eight obese and
      eight normal-weight boys walking at their self-selected speed. The compressive
      tibiofemoral force and individual muscle contribution to the support and
      progression accelerations of center of mass (COM) were computed for each
      participant based on the subject-specific model. The simulated results were
      verified by comparing them to the experimental kinematics and EMG data. We found
      a linear relationship between the average self-selected speed and the normalized
      peak compressive tibiofemoral force (R (2) = 0.611). The activity of the
      quadriceps contributed the most to the peak compressive tibiofemoral force during
      the stance phase. Obese children and nonobese children use similar muscles to
      support and accelerate the body COM, but nonobese children had significantly
      greater contributions of individual muscles. The obese children may therefore
      adopt a compensation strategy to avoid increasing joint loads and muscle
      requirements during walking. The absolute compressive tibiofemoral force and
      muscle forces were still greater in obese children. The long-term biomechanical
      adaptations of the musculoskeletal system to accommodate the excess body weight
      during walking are a concern. 

PMID- 24288574
TI  - Determination of fetal state from cardiotocogram using LS-SVM with particle swarm
      optimization and binary decision tree.
AB  - We use least squares support vector machine (LS-SVM) utilizing a binary decision
      tree for classification of cardiotocogram to determine the fetal state. The
      parameters of LS-SVM are optimized by particle swarm optimization. The robustness
      of the method is examined by running 10-fold cross-validation. The performance of
      the method is evaluated in terms of overall classification accuracy.
      Additionally, receiver operation characteristic analysis and cobweb
      representation are presented in order to analyze and visualize the performance of
      the method. Experimental results demonstrate that the proposed method achieves a
      remarkable classification accuracy rate of 91.62%. 

PMID- 24288575
TI  - Robust joint analysis with data fusion in two-stage quantitative trait genome
      wide association studies.
AB  - Genome-wide association studies (GWASs) in identifying the disease-associated
      genetic variants have been proved to be a great pioneering work. Two-stage design
      and analysis are often adopted in GWASs. Considering the genetic model
      uncertainty, many robust procedures have been proposed and applied in GWASs.
      However, the existing approaches mostly focused on binary traits, and few work
      has been done on continuous (quantitative) traits, since the statistical
      significance of these robust tests is difficult to calculate. In this paper, we
      develop a powerful F-statistic-based robust joint analysis method for
      quantitative traits using the combined raw data from both stages in the framework
      of two-staged GWASs. Explicit expressions are obtained to calculate the
      statistical significance and power. We show using simulations that the proposed
      method is substantially more robust than the F-test based on the additive model
      when the underlying genetic model is unknown. An example for rheumatic arthritis
      (RA) is used for illustration. 

PMID- 24288576
TI  - Complex codon usage pattern and compositional features of retroviruses.
AB  - Retroviruses infect a wide range of organisms including humans. Among them, HIV
      1, which causes AIDS, has now become a major threat for world health. Some of
      these viruses are also potential gene transfer vectors. In this study, the
      patterns of synonymous codon usage in retroviruses have been studied through
      multivariate statistical methods on ORFs sequences from the available 56
      retroviruses. The principal determinant for evolution of the codon usage pattern
      in retroviruses seemed to be the compositional constraints, while selection for
      translation of the viral genes plays a secondary role. This was further supported
      by multivariate analysis on relative synonymous codon usage. Thus, it seems that
      mutational bias might have dominated role over translational selection in shaping
      the codon usage of retroviruses. Codon adaptation index was used to identify
      translationally optimal codons among genes from retroviruses. The comparative
      analysis of the preferred and optimal codons among different retroviral groups
      revealed that four codons GAA, AAA, AGA, and GGA were significantly more frequent
      in most of the retroviral genes inspite of some differences. Cluster analysis
      also revealed that phylogenetically related groups of retroviruses have probably
      evolved their codon usage in a concerted manner under the influence of their
      nucleotide composition. 

PMID- 24288577
TI  - Application of genetic algorithm for discovery of core effective formulae in TCM
      clinical data.
AB  - Research on core and effective formulae (CEF) does not only summarize traditional
      Chinese medicine (TCM) treatment experience, it also helps to reveal the
      underlying knowledge in the formulation of a TCM prescription. In this paper, CEF
      discovery from tumor clinical data is discussed. The concepts of confidence,
      support, and effectiveness of the CEF are defined. Genetic algorithm (GA) is
      applied to find the CEF from a lung cancer dataset with 595 records from 161
      patients. The results had 9 CEF with positive fitness values with 15 distinct
      herbs. The CEF have all had relative high average confidence and support. A herb
      herb network was constructed and it shows that all the herbs in CEF are core
      herbs. The dataset was divided into CEF group and non-CEF group. The effective
      proportions of former group are significantly greater than those of latter group.
      A Synergy index (SI) was defined to evaluate the interaction between two herbs.
      There were 4 pairs of herbs with high SI values to indicate the synergy between
      the herbs. All the results agreed with the TCM theory, which demonstrates the
      feasibility of our approach. 

PMID- 24288578
TI  - Adolescent Resilience: Promotive Factors That Inform Prevention.
AB  - Resilience theory provides a framework for studying and understanding how some
      youths overcome risk exposure and guides the development of interventions for
      prevention using a strengths-based approach. In this article, we describe basic
      concepts of the theory, such as promotive factors, and distinguish assets and
      resources that help youths overcome the negative effects of risk exposure. We
      also present three models of resilience theory-compensatory, protective, and
      challenge-and review empirical research on three promotive factors-ethnic
      identity, social support, and prosocial involvement-that include individual,
      family, and community levels of analysis and have modifiable qualities for
      informing interventions. Finally, we present examples of how research findings
      from the three promotive factors can be translated into interventions to enhance
      youth development.

PMID- 24288579
TI  - Comparison of bottom-up proteomic approaches for LC-MS analysis of complex
      proteomes.
AB  - Discovery-based proteomic studies aim to answer important biological questions by
      identifying as many proteins as possible. In order to accomplish this lofty goal,
      an effort must be placed on determining an optimal workflow that maximizes
      protein identifications. In this study, we compare protein extraction, digestion
      and fractionation methods for bottom-up proteomics using a human colon cancer
      cell line as our model system. Four different buffers for protein extraction, two
      digestion approaches, as well as three sample fractionation methods were
      evaluated in order to determine an accessible workflow that gives maximal protein
      identifications. Samples comparing these workflows were analyzed via UPLC paired
      with tandem MS on a Q-Exactive mass spectrometer. Our goal is to determine an
      optimal workflow to enable users to maximize protein identifications. Our results
      show that an increased number of confident protein identifications are attained
      with a filter-aided digestion approach as compared to an in-solution digestion.
      Overall SDS-PAGE fractionation leads to higher numbers of identifications than
      SCX SpinTip and reverse phased cartridge platforms. The novel aspect of this work
      is the comparison of two readily available, offline platforms for fractionation
      in reference to a traditional technique, SDS-PAGE.

PMID- 24288580
TI  - Clinicians' Use of Personality Disorder Models within a Particular Treatment
      Setting: A Longitudinal Comparison of Temporal Consistency and Clinical Utility.
AB  - An active line of current investigation is how the five-factor model (FFM) of
      personality disorder might be applied by clinicians and particularly, how
      clinically useful this model is in comparison to the existing nomenclature. The
      current study is the first to investigate the temporal consistency of clinicians'
      application of the FFM and the DSM-IV-TR to their own patients. Results indicated
      that FFM ratings were relatively stable over six-months of treatment, supporting
      their use by clinicians, but also indexed potentially important clinical changes.
      Additionally, ratings of utility provided by the clinicians suggested that the
      FFM was more useful for clinical decision making than was the DSM-IV-TR model. We
      understand the clinical utility findings within the context of previous research
      indicating that the FFM is most useful among patients who are not prototypic for
      a personality disorder.

PMID- 24288581
TI  - A Public Health Approach to Improving the Lives of Adult Learners: Introduction
      to the Special Issue on Adult Literacy Interventions.
AB  - Addressing the literacy needs of adult basic and secondary education learners
      must form a core part of a broader public health effort to increase educational
      and health outcomes for these individuals and their families. Adult learners
      constitute a significant proportion of the overall adult U.S. population and a
      proportion that impacts, directly and indirectly, on the physical and economic
      health of millions of families and society writ large. Enhancing the literacy
      skills of low literate adults has proven difficult, hampered by the relative
      dearth of research data on struggling adult learners and effective intervention
      approaches, the contextual challenges of delivering intensive interventions,
      limited personal and systemic resources, and competing demands on learners' time.
      We propose a systems level view of adult low-literacy as one that holds promise
      and provides a basic framework for providing coordinated, comprehensive, and
      integrated services, but that requires additional research to support. Informed
      and coordinated efforts with the pre-kindergarten to twelfth grade education
      system and health and labor services sectors is needed if we are to improve the
      lives of these adults and their families.

PMID- 24288582
TI  - Punctal plugs versus artificial tears for treating dry eye: a comparative
      observation of their effects on contrast sensitivity.
AB  - This study aimed to compare the effects of treatment with punctal plugs versus
      artificial tears on visual function and tear film stability for dry eye. A total
      of 56 consecutive eyes of 28 dry eye patients observed at our clinic from May to
      October in 2009 were divided into two groups. One group (32 eyes of 16 patients)
      was treated with artificial tears, and punctal plugs were used in the other group
      (24 eyes of 12 patients). A questionnaire was used in these patients before
      treatment and was repeated 2 weeks after treatment. Fluorescent staining for tear
      film break-up time (BUT), the Schirmer test I (STI), and contrast sensitivity was
      performed at the same time. The questionnaire indicated that all patients
      complained about the uncomfortable symptoms associated with dry eye. These
      symptoms were relieved after the application of artificial tears or punctal
      plugs, and there was no significant difference between these two groups. We found
      that the corneal fluorescent staining disappeared after treatment. The BUT was
      improved significantly after treatment in both groups, but the improvement was
      greater in patients who received punctal plugs than those that received
      artificial tears. There was no remarkable change in the STI in the artificial
      tears group, but a significant change was observed in the punctal plugs group.
      The contrast sensitivities were greatly improved in simulated daylight, night,
      and glare disability conditions after treatment with artificial tears and punctal
      plugs. However, the changes in contrast sensitivity did not significantly differ
      between groups. Both artificial tears and punctal plugs relieved dry eye
      symptoms, repaired corneal lesions, enhanced tear film stability, and improved
      contrast sensitivity. Punctal plugs could improve tear film stability and
      elongate the BUT better than artificial tears. 

PMID- 24288583
TI  - The natural stilbenoid piceatannol decreases activity and accelerates apoptosis
      of human neutrophils: involvement of protein kinase C.
AB  - Neutrophils are able to release cytotoxic substances and inflammatory mediators,
      which, along with their delayed apoptosis, have a potential to maintain permanent
      inflammation. Therefore, treatment of diseases associated with chronic
      inflammation should be focused on neutrophils; formation of reactive oxygen
      species and apoptosis of these cells represent two promising targets for
      pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has
      the ability to reduce the toxic action of neutrophils. This substance decreased
      the amount of oxidants produced by neutrophils both extra- and intracellularly.
      Radicals formed within neutrophils (fulfilling a regulatory role) were reduced to
      a lesser extent than extracellular oxidants, potentially dangerous for host
      tissues. Moreover, piceatannol did not affect the phosphorylation of p40(phox)-a
      component of NADPH oxidase, responsible for the assembly of functional oxidase in
      intracellular (granular) membranes. The stilbenoid tested elevated the percentage
      of early apoptotic neutrophils, inhibited the activity of protein kinase C (PKC)
      the main regulatory enzyme in neutrophils, and reduced phosphorylation of PKC
      isoforms alpha , beta II, and delta on their catalytic region. The results
      indicated that piceatannol may be useful as a complementary medicine in states
      associated with persisting neutrophil activation and with oxidative damage of
      tissues.

PMID- 24288584
TI  - Quercetin induces mitochondrial biogenesis through activation of HO-1 in HepG2
      cells.
AB  - The regeneration of mitochondria by regulated biogenesis plays an important
      homeostatic role in cells and tissues and furthermore may provide an adaptive
      mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon
      monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells.
      Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO
      1/CO system. This study focused on the mechanism by which the natural antioxidant
      quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that
      quercetin treatment induced expression of mitochondrial biogenesis activators
      (PGC-1 alpha , NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in
      HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the
      effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory
      effects of quercetin on mitochondrial biogenesis could be recapitulated in vivo
      in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti
      inflammatory effect in the liver of mice treated with LPS and prevented
      impairment of mitochondrial biogenesis by LPS in vivo. These salutary effects of
      quercetin in vivo were also antagonized by SnPP. Thus, our results suggest that
      quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system in
      vitro and in vivo. The beneficial effects of quercetin may provide a therapeutic
      basis in inflammatory diseases and sepsis. 

PMID- 24288585
TI  - Effects of endothelial progenitor cell-derived microvesicles on
      hypoxia/reoxygenation-induced endothelial dysfunction and apoptosis.
AB  - Oxidative stress-induced endothelial dysfunction plays a key role in
      ischemia/reperfusion injury. Recent evidence indicates that endothelial
      progenitor cell-derived microvesicles (EPC-MVs) can promote angiogenesis of
      endothelial cells (ECs). Here, we investigated the potential effects of EPC-MVs
      on hypoxia/reoxygenation (H/R) injury in human brain microvascular ECs (hb-ECs).
      MVs were prepared from EPCs cultured in a serum deprivation (SD) medium (starving
      stress, sEPC-MVs) or SD medium containing tumor necrosis factor- alpha (TNFalpha)
      (apoptotic stress, aEPC-MVs). H/R injury model of hb-ECs was produced by 6 hr
      hypoxia (1% O2) and 24 hr reoxygenation. The H/R hb-ECs were co-cultured with EPC
      MVs. Results showed that (1) H/R hb-ECs were dysfunctional and coupled with
      increased apoptosis and ROS overproduction; (2) under two different conditions,
      EPCs displayed remarkable difference in caspase 3 and miR126 expression, which
      were carried by the corresponsive EPC-MVs; (3) functionally, sEPC-MVs had
      beneficial effects on H/R hb-ECs, whereas aEPC-MVs had detrimental effects; (4)
      the diverse effects of sEPC-MVs and aEPC-MVs were associated with the changes in
      miR126 and eNOS expression and were abolished by PI3K inhibitor. In conclusion,
      sEPCs-MVs and aEPC-MVs are functionally different on hb-EC apoptosis and
      dysfunction via their carried RNAs associated with ROS production and
      PI3K/eNOS/NO pathway.

PMID- 24288586
TI  - Analysis of House Dust and Children's Hair for Pesticides: A Comparison of
      Markers of Ongoing Pesticide Exposure in Children.
AB  - BACKGROUND/AIM: The long term study of the adverse effects of pesticides on child
      neuro development requires monitoring not only of initial, but ongoing pesticide
      exposure. Our aim was to compare house dust and children's hair as environmental
      and biological markers of ongoing pesticide exposure in children. DESIGN/METHODS:
      In a continuing NIH study on the adverse effects of prenatal pesticide exposure
      on child neurodevelopment, ongoing pesticide exposure after birth was measured in
      swept house dust and hair in the children at 4 years of age for propoxur and
      pyrethroids (transfluthrin, bioallethrin, cyfluthrin and cypermethrin) by gas
      chromatography/mass spectrometry. The prevalence and concentration of pesticides
      in the two matrices were compared. RESULTS: Prevalence of propoxur was higher in
      hair compared to house dust (p<0.001) whereas prevalence of the pyrethroids was
      higher (p<0.001) in house dust. The overall concentrations of the pyrethroids
      were also higher (p<0.007) in house dust compared to hair. There was a
      significant (p<0.001) correlation between dust and hair for bioallethrin and
      cypermethrin. CONCLUSIONS: Ongoing exposure of children to environmental
      pesticides is sensitively detected by analysis of children's hair and house dust.
      However, prevalence of propoxur was higher in hair compared to swept house dust,
      but the opposite was found for the pyrethroids. Thus, both matrices should be
      analyzed. There was a significant (p<0.001) correlation between house dust and
      hair for bioallethrin and cypermethrin.

PMID- 24288587
TI  - Lipid-Coated Nanoscale Coordination Polymers for Targeted Delivery of Antifolates
      to Cancer Cells.
AB  - Nanoscale coordination polymers (NCPs) have been demonstrated as an interesting
      platform for drug delivery, as they possess many advantages over small-molecule
      chemotherapeutics, such as high payloads, lower systemic toxicity, tunability,
      and enhanced tumor uptake. Existing formulations for the delivery of methotrexate
      (MTX), an antifolate cancer drug, have very low drug loadings. Herein, we report
      the incorporation of MTX as a building block in an NCP formulation with
      exceptionally high drug loadings (up to 79.1 wt%) and the selective delivery of
      the NCP to cancer cells. Encapsulation of the NCP in a functionalized lipid
      bilayer allows for targeted delivery and controlled release to cancer cells. A
      phosphor can be doped into the NCPs for monitoring particle uptake by optical
      imaging. The lipid-coated and anisamide-targeted NCPs have superior in vitro
      efficacy against acute lymphoblastic leukemia cells when compared to free drug.

PMID- 24288588
TI  - Nitric oxide-flux dependent bacterial adhesion and viability at fibrinogen-coated
      surfaces.
AB  - Nitric oxide (NO) is an endogenous antibacterial agent produced by immune cells
      in response to pathogens. Herein, the NO fluxes necessary to reduce bacterial
      adhesion of different bacteria (S. aureus, methicillin-resistant S. aureus, S.
      epidermidis, E. faecalis, E. coli, and P. aeruginosa) were investigated to
      ascertain the sensitivity of these bacteria to NO. S-nitrosothiol NO donor
      modified xerogels were selected as a model NO-release surface due to their
      extended NO-release kinetics relative to other NO donor systems. The xerogels
      were coated with poly(vinyl chloride) (PVC) to achieve consistent surface energy
      between NO-releasing and control substrates. Fibrinogen was pre-adsorbed to these
      materials to more accurately mimic conditions encountered in blood and promote
      bacteria adhesion. Nitric oxide fluxes ranging from 20-50 pmol cm-2 s-1
      universally inhibited the bacterial adhesion by >80% for each strain studied.
      Maximum bacteria killing activity (reduced viability by 85-98%) was observed at
      the greatest NO payload (1700 nmol cm-2).

PMID- 24288589
TI  - Bismuth@US-tubes as a Potential Contrast Agent for X-ray Imaging Applications.
AB  - The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single
      walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have
      been characterized by high-resolution transmission electron microscopy (HR-TEM),
      energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X
      ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have
      been used for intracellular labeling of pig bone marrow-derived mesenchymal stem
      cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular
      imaging for the first time. The relatively high contrast is achieved with low
      bismuth loading (2.66% by weight) within the US-tubes and without compromising
      cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two
      fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV
      CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times
      greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any
      clinical iodinated contrast agent (CA) at the same concentration. Our findings
      suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT
      agent for stem cell labeling and possibly in vivo tracking.

PMID- 24288590
TI  - Towards dynamical network biomarkers in neuromodulation of episodic migraine.
AB  - Computational methods have complemented experimental and clinical neurosciences
      and led to improvements in our understanding of the nervous systems in health and
      disease. In parallel, neuromodulation in form of electric and magnetic
      stimulation is gaining increasing acceptance in chronic and intractable diseases.
      In this paper, we firstly explore the relevant state of the art in fusion of both
      developments towards translational computational neuroscience. Then, we propose a
      strategy to employ the new theoretical concept of dynamical network biomarkers
      (DNB) in episodic manifestations of chronic disorders. In particular, as a first
      example, we introduce the use of computational models in migraine and illustrate
      on the basis of this example the potential of DNB as early-warning signals for
      neuromodulation in episodic migraine.

PMID- 24288591
TI  - Neutrophil gelatinase-associated lipocalin in kidney transplantation is an early
      marker of graft dysfunction and is associated with one-year renal function.
AB  - Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as
      potential early marker of delayed graft function (DGF) following kidney
      transplantation (KTx). We conducted a prospective study in 40 consecutive KTx
      recipients to evaluate serial changes of uNGAL within the first week after KTx
      and assess its performance in predicting DGF (dialysis requirement during initial
      posttransplant week) and graft function throughout first year. Urine samples were
      collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable
      regression models, receiver-operating characteristic (ROC), and areas under ROC
      curves were used. At all-time points, mean uNGAL levels were significantly higher
      in patients developing DGF (n = 18). Shortly after KTx (3-6 h), uNGAL values were
      higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time
      of 4.1 years) and rose further in following days, contrasting with prompt
      function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC =
      0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and
      similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that
      uNGAL levels at days 4 and 7 were strongly associated with one-year serum
      creatinine. Urinary NGAL is an early marker of graft injury and is independently
      associated with dialysis requirement within one week after KTx and one-year graft
      function. 

PMID- 24288592
TI  - Circulating CD4(+)CD28null T Cells May Increase the Risk of an Atherosclerotic
      Vascular Event Shortly after Kidney Transplantation.
AB  - Proinflammatory CD4(+) T cells without the costimulatory molecule CD28
      (CD4(+)CD28null T cells) are expanded in patients with end-stage renal disease
      (ESRD) and associated with atherosclerotic vascular events (AVE). In a
      prospective study, the number of circulating CD4(+)CD28null T cells was
      established in 295 ESRD patients prior to receiving a kidney allograft. Within
      the first year after transplantation, an AVE occurred in 20 patients. Univariate
      analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1,
      P < 0.001), age (HR 1.04, P = 0.02), dyslipidaemia (HR 8.8, P = 0.004), and the %
      of CD4(+)CD28null T cells (HR 1.04 per % increase, 95% CI 1.00-1.09, P = 0.01)
      were significantly associated with the occurrence of a posttransplantation AVE.
      In a multivariate analysis, only CVDpos remained a significant risk factor with a
      significant and positive interaction between the terms CVDpos and the % of
      CD4(+)CD28null T cells (HR 1.05, 95% CI 1.03-1.11, P < 0.001). Within the CVDpos
      group, the incidence of an AVE was 13% in the lowest tertile compared to 25% in
      the highest tertile of % of CD4(+)CD28null T cells. In conclusion, the presence
      of circulating CD4(+)CD28null T cells is associated with an increased risk for a
      cardiovascular event shortly after kidney transplantation. 

PMID- 24288593
TI  - RNA Interference Targeting Connective Tissue Growth Factor Inhibits the
      Transforming Growth Factor- beta 2 Induced Proliferation in Human Tenon Capsule
      Fibroblasts.
AB  - Purpose. This study was to determine the effect of CTGF-small interfering RNA
      (siRNA) on TGF- beta 2-induced proliferation in human Tenon capsule fibroblasts
      (HTFs). Methods. HTFs were transfected with four of CTGF-siRNAs separately for
      screening of gene silencing efficacy that was determined by transcript level
      measured by quantitative real-time PCR (qRT-PCR). Recombinant TGF- beta 2 was
      added into the culture to stimulate the proliferation of HTFs. The gene silencing
      efficacy of the siRNAs was evaluated by qRT-PCR and immunofluorescence of CTGF
      transcript and protein levels. The viability of HTFs was determined by cell
      counting kit-8 (CCK-8). FCM was used to assess cell cycle after CTGF-siRNA
      transfection. Results. The expression of CTGF and proliferation of HTFs were
      increased significantly by TGF- beta 2 stimulation. The transfection of CTGF
      siRNA abolished the upregulation of CTGF and cell proliferation induced by TGF-
      beta 2. The analysis of cell cycle indicated that CTGF-siRNA treatment stimulated
      cells from S phase to G0/G1 phase in comparison with the inverse physiologic
      function of TGF- beta 2. Conclusion. CTGF targeting siRNA could effectively
      suppress the expression of CTGF and attenuate the proliferation of HTFs. The
      siRNA approach may provide a therapeutic option for eliminating filtration bleb
      scarring after glaucoma filtration surgery (GFS). 

PMID- 24288594
TI  - Three-Dimensional Multidetector CT for Anatomic Evaluation of Orbital Tumors.
AB  - Intricate resection and complex reconstructive procedures often required for
      primary and metastatic orbital tumors are facilitated by accurate imaging. A
      three-dimensional (3D) image can be reconstructed from source axial multidetector
      computed tomography (MDCT) images to visualize orbital tumors. To assess the
      utility of 3D images in this setting, the 3D images were reconstructed
      retrospectively for 20 patients with an orbital tumor and compared to two
      dimensional (2D) orthogonal MDCT studies. Both types of images were assessed for
      their capacity to show the bony orbital walls and foramina, extraocular muscles,
      and optic nerve in the orbit contralateral to the tumor and, in the affected
      orbit, the extent of the tumor and its relationship to normal orbital contents
      and associated bone destruction. 3D imaging is most informative when axial images
      are acquired at 1.25 mm collimation. The optic nerve, extraocular muscles, and
      well-circumscribed orbital tumors were well visualized on 3D images. On 3D
      imaging, tumor-associated destruction of the lateral and superior orbital walls
      was fairly well demonstrated and that of the inferior and medial walls was not.
      The 3D images provide the surgeon with a comprehensive view of well-circumscribed
      orbital tumors and its relationship to extraocular muscles, exiting foramina, and
      the superior and lateral walls. 

PMID- 24288595
TI  - Immobilization of DNA aptamers on polyester cloth for antigen detection by dot
      blot immunoenzymatic assay (aptablot).
AB  - A simple dot blot immunoenzymatic assay system was developed using polyester
      cloth coated with an oligo-DNA aptamer to provide a high-affinity macroporous
      surface for the efficient capture of a model protein analyte (thrombin) in
      complex sample matrices such as foods. Bound thrombin was detected
      immunoenzymatically using a peroxidase-linked antithrombin antibody and a
      chromogenic substrate. A unique feature of this approach, which we have termed
      "aptablot," is the facile immobilization of DNA aptamers on the polyester surface
      by cross-linking with a brief exposure to ultraviolet light, and the simple assay
      format obviating the need for specialized instruments. The assay principle
      described herein should be broadly applicable to many situations where analytes
      must be detected in complex samples, with the main limiting factor being the
      availability of suitable DNA aptamers. 

PMID- 24288596
TI  - Genetic and Adverse Health Outcome Associations with Treatment Resistant
      Hypertension in GenHAT.
AB  - Treatment resistant hypertension (TRH) is defined as uncontrolled hypertension
      (HTN) despite the use of >=3 antihypertensive medication classes or controlled
      HTN while treated with >=4 antihypertensive medication classes. Risk factors for
      TRH include increasing age, diminished kidney function, higher body mass index,
      diabetes, and African American (AA) race. Importantly, previous studies suggest a
      genetic role in TRH, although the genetics of TRH are largely understudied. With
      2203 treatment resistant cases and 2354 treatment responsive controls (36% AA)
      from the Genetics of Hypertension Associated Treatment Study (GenHAT), we
      assessed the association of 78 candidate gene polymorphisms with TRH status using
      logistic regression. After stratifying by race and adjusting for potential
      confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051)
      statistically significantly associated with TRH among white participants. The Met
      allele of rs699 and the G allele of rs5051 were positively associated with TRH:
      OR = 1.27 (1.12-1.44), P = 0.0001, and OR = 1.36 (1.20-1.53), P < 0.0001,
      respectively. There was no similar association among AA participants (race
      interaction P = 0.0004 for rs699 and P = 0.0001 for rs5051). This research
      contributes to our understanding of the genetic basis of TRH, and further genetic
      studies of TRH may help reach the goal of better clinical outcomes for
      hypertensive patients. 

PMID- 24288598
TI  - Clinical spectrum of propionic acidaemia.
AB  - Objectives. To evaluate the clinical features, physical findings, diagnosis, and
      laboratory parameters of the patients with propionic acidaemia (PA). Methods. The
      records of diagnosed cases of propionic acidaemia were reviewed, retrospectively.
      Results. Twenty-six patients with PA had 133 admissions. The majority (85%) of
      the patients exhibited clinical manifestations in the 1st week of life. Regarding
      clinical features, lethargy, fever, poor feeding, vomiting, dehydration, muscular
      hypotonia, respiratory symptoms, encephalopathy, disturbance of tone and
      reflexes, and malnutrition were observed in 51-92% admissions. Metabolic crises,
      respiratory diseases, hyperammonaemia, metabolic acidosis, hypoalbuminaemia, and
      hypocalcaemia were observed in 30-96% admissions. Pancytopenia, ketonuria,
      hypoproteinemia, hypoglycaemia, and mildly disturbed liver enzymes were found in
      12-41% admissions. Generalised brain oedema was detected in 17% and cerebral
      atrophy in 25% admissions. Gender-wise odd ratio analysis showed value of 1.9 for
      lethargy, 1.99 for respiratory diseases, 0.55 for anaemia, and 1.82 for
      hypocalcaemia. Conclusion. Propionic acidaemia usually presents with wide
      spectrum of clinical features and disturbances of laboratory parameters in early
      neonatal age. It is associated with significant complications which deteriorate
      the patients' quality of life. Perhaps with early diagnosis of the disease and in
      time intervention, these may be preventable. 

PMID- 24288597
TI  - Immobilization technologies in probiotic food production.
AB  - Various supports and immobilization/encapsulation techniques have been proposed
      and tested for application in functional food production. In the present review,
      the use of probiotic microorganisms for the production of novel foods is
      discussed, while the benefits and criteria of using probiotic cultures are
      analyzed. Subsequently, immobilization/encapsulation applications in the food
      industry aiming at the prolongation of cell viability are described together with
      an evaluation of their potential future impact, which is also highlighted and
      assessed. 

PMID- 24288599
TI  - Serum iron status of under-five children with sickle cell anaemia in lagos,
      Nigeria.
AB  - Background. Iron status in patients with sickle cell anaemia is a matter of
      continuing investigation. Objective. This paper aims to determine the serum iron
      status of under-five, sickle cell anaemia patients. Methods. The study spanned
      from December 2009 to February 2010 at the Consultant Outpatient Clinics
      involving 97 HbSS subjects and 97 age- and sex-matched HbAA controls. Biochemical
      iron status was assayed in subjects and controls. Results. Age range of the
      children was seven months to five years, with a mean of 30.6 (+/-15.97) months.
      Irrespective of gender, mean serum iron values were higher in HbAA controls than
      their HbSS counterparts but the observed difference was not significant (P =
      0.299 and 0.111, resp.). The mean total iron binding capacity values of males and
      females were also not significantly different for sickle cell anaemia subjects
      and controls (P > 0.05). Males and females with HbAA had significantly lower
      serum ferritin when compared with their HbSS counterparts. Irrespective of
      gender, mean transferrin saturation was lower in HbSS subjects but the difference
      was not statistically significant (P > 0.05). Conclusion. Children with sickle
      cell anaemia have higher serum ferritin than controls, implying relatively higher
      iron content in the reticuloendothelial cells. 

PMID- 24288600
TI  - Excessive daytime sleepiness and epilepsy: a systematic review.
AB  - Background. Sleep complaints are common in patients with epilepsy (PWE).
      Excessive daytime sleepiness (EDS) is one of the most reported complaints and its
      impact is still a matter of debate. Objective. Evaluate the relationship between
      EDS and epilepsy, with emphasis on prevalence, assessment, and causes. Methods. A
      systematic review on PubMed database in the last 10 years (2002 to 2012). The
      search returned 53 articles and 34 were considered relevant. After citation
      analysis, 3 more articles were included. Results. Most studies were cross
      sectional and questionnaire based. 14 papers addressed EDS as the primary
      endpoint. 14 adult and 3 children studies used subjective and objective analysis
      as methodology. The number of studies increased throughout the decade, with 21 in
      the last 5 years. Adult studies represent almost three times the number of
      children studies. EDS prevalence in PWE varies from 10 to 47.5%. Prevalence was
      higher in developing countries. Conclusion. EDS seems to be related more
      frequently to undiagnosed sleep disorders than to epilepsy-related factors, and
      although it affects the quality of life of PWE, it can be improved by treating
      comorbid primary sleep disorders. 

PMID- 24288601
TI  - Surgical treatment of pediatric epileptic encephalopathies.
AB  - Pediatric epileptiform encephalopathies are a group of neurologically devastating
      disorders related to uncontrolled ictal and interictal epileptic activity, with a
      poor prognosis. Despite the number of pharmacological options for treatment of
      epilepsy, many of these patients are drug resistant. For these patients with
      uncontrolled epilepsy, motor and/or neuropsychological deterioration is common.
      To prevent these secondary consequences, surgery is often considered as either a
      curative or a palliative option. Magnetic resonance imaging to look for epileptic
      lesions that may be surgically treated is an essential part of the workup for
      these patients. Many surgical procedures for the treatment of epileptiform
      encephalopathies have been reported in the literature. In this paper the evidence
      for these procedures for the treatment of pediatric epileptiform encephalopathies
      is reviewed. 

PMID- 24288602
TI  - Temporal lobe resective surgery for medically intractable epilepsy: a review of
      complications and side effects.
AB  - Object. It is widely accepted that temporal resective surgery represents an
      efficacious treatment option for patients with epilepsy of temporal origin. The
      meticulous knowledge of the potential complications, associated with temporal
      resective procedures, is of paramount importance. In our current study, we
      attempt to review the pertinent literature for summating the complications of
      temporal resective procedures for epilepsy. Method. A PubMed search was performed
      with the following terms: "behavioral," "cognitive," "complication," "deficit,"
      "disorder," "epilepsy," "hemianopia," "hemianopsia," "hemorrhage," "lobectomy,"
      "medial," "memory," "mesial," "neurobehavioral," "neurocognitive,"
      "neuropsychological," "psychological," "psychiatric," "quadranopia,"
      "quadranopsia," "resective," "side effect," "surgery," "temporal," "temporal
      lobe," and "visual field." Results. There were six pediatric, three mixed
      population, and eleven adult surgical series examining the incidence rates of
      procedure-related complications. The reported mortality rates varied between 0%
      and 3.5%, although the vast majority of the published series reported no
      mortality. The cumulative morbidity rates ranged between 3.2% and 88%.
      Conclusions. Temporal resective surgery for epilepsy is a safe treatment
      modality. The reported morbidity rates demonstrate a wide variation. Accurate
      detection and frank reporting of any surgical, neurological, cognitive, and/or
      psychological complications are of paramount importance for maximizing the safety
      and improving the patients' overall outcome. 

PMID- 24288603
TI  - Circulating cytokines and histological liver damage in chronic hepatitis B
      infection.
AB  - Each phase of hepatitis B infection stimulates distinct viral kinetics and host
      immune responses resulting in liver damage and hepatic fibrosis. Our objective
      has been to correlate host inflammatory immune response including circulating Th1
      and Th2 cytokines in patients with chronic hepatitis B infection with liver
      histopathology. Sixty-four patients with chronic hepatitis B without previous
      treatment were recruited. The liver histology and histological activity index
      were assessed for various degrees of necroinflammation and hepatic fibrosis. We
      determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and
      18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64
      (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma
      were significantly correlated with degrees of necroinflammation (r = 0.34, r =
      0.38, resp.; P < 0.05). Moreover, TNF-alpha was significantly correlated with
      degrees of fibrosis (r = 0.35; P < 0.05), and IL-10 and TNF-alpha were
      significantly correlated with significant fibrosis (r = 0.39, r = 0.35, resp.; P
      < 0.05). These correlations were found in the HBeAg negative group as opposed to
      the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10
      and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10
      and TNF-alpha were correlated with significant fibrosis. 

PMID- 24288604
TI  - Risk perception and risk communication for training women apprentice welders: a
      challenge for public health nursing.
AB  - This research has aimed to identify the perceptions of women apprentice welders
      about physical, chemical, biological, and physiological risk factors to which
      they are exposed and evaluate the identification of health disorders self
      reported for women apprentice welders before and after implementation of a
      nursing socioenvironmental intervention. A quantitative study was performed with
      27 women apprentice welders (first phase) and before and after an intervention
      with 18 women (second phase) in Southern Brazil in 2011. The data were analysed
      using SPSS 19.0. The participants identified the following risk types: physical
      (96.2%), chemical (96.2%), physiological (88.8%), and biological (62.9%). The
      results show a significant difference of the pre- and posttest averages for the
      musculoskeletal system and a posttest average increase for the integumentary,
      respiratory, and auditory system. A correlation of the women apprentices' ages
      and the identification of health disorders were made. It was understood that the
      perception of women apprentices regarding a particular set of occupational risks
      is essential for public health nursing to develop an effective risk communication
      as a positive tool for teaching and learning. 

PMID- 24288605
TI  - Regulation of vascular function on posttranscriptional level.
AB  - Posttranscriptional control of gene expression is crucial for regulating
      plurality of proteins and functional plasticity of the proteome under
      (patho)physiologic conditions. Alternative splicing as well as micro (mi)RNA
      mediated mechanisms play an important role for the regulation of protein
      expression on posttranscriptional level. Both alternative splicing and miRNAs
      were shown to influence cardiovascular functions, such as endothelial
      thrombogenicity and the vascular tone, by regulating the expression of several
      vascular proteins and their isoforms, such as Tissue Factor (TF) or the
      endothelial nitric oxide synthase (eNOS). This review will summarize and discuss
      the latest findings on the (patho)physiologic role of alternative splicing
      processes as well as of miRNAs on modulation of vascular functions, such as
      coagulation, thrombosis, and regulation of the vascular tone. 

PMID- 24288606
TI  - The Role of Cardiopulmonary Exercise Test in IPF Prognosis.
AB  - Background. In IPF, defects in lung mechanics and gas exchange manifest with
      exercise limitation due to dyspnea, the most prominent and disabling symptom.
      Aim. To evaluate the role of exercise testing through the 6MWT (6-minute walk
      test) and CPET (cardiopulmonary exercise testing) in the survival of patients
      with IPF. Methods. This is a prospective, observational study evaluating in 25
      patients the relationship between exercise variables through both the 6MWT and
      CPET and survival. Results. By the end of the observational period 17 patients
      were alive (33% mortality). Observation ranged from 9 to 64 months. VE/VCO2 slope
      (slope of relation between minute ventilation and CO2 production), VO2 peak/kg
      (peak oxygen consumption/kg), VE/VCO2 ratio at anaerobic threshold, 6MWT
      distance, desaturation, and DLCO% were significant predictors of survival while
      VE/VCO2 slope and VO2 peak/kg had the strongest correlation with outcome. The
      optimal model for mortality risk estimation was VO2 peak/kg + DLCO% combined.
      Furthermore, VE/VCO2 slope and VO2 peak/kg were correlated with distance and
      desaturation during the 6MWT. Conclusion. The integration of oxygen consumption
      and diffusing capacity proved to be a reliable predictor of survival because both
      variables reflect major underlying physiologic determinants of exercise
      limitation. 

PMID- 24288607
TI  - The Relationship between Comprehension of Figurative Language by Japanese
      Children with High Functioning Autism Spectrum Disorders and College Freshmen's
      Assessment of Its Conventionality of Usage.
AB  - Unlike their English-speaking counterparts, Japanese children with high
      functioning autism spectrum disorders (HFASDs) perform as well as typically
      developing (TD) children in comprehending metaphor, despite lacking 1st order
      theory of mind (ToM) reasoning. Additionally, although Japanese sarcasm and
      "indirect reproach" appear theoretically to need 2nd order ToM reasoning, HFASD
      children without this comprehended these forms of language as well as TD
      children. To attempt to explain this contradiction, we asked college freshmen to
      evaluate the strangeness (unconventionality) of these types of figurative
      language. We aimed to test the hypothesis that metaphor, sarcasm, and "indirect
      reproach" might be evaluated as more conventional than irony, which children with
      HFASDs do not comprehend as well as those with attention deficit hyperactivity
      disorder. The results for irony, metaphor, and "indirect reproach" supported the
      hypothesis, while those for sarcasm did not. Sarcasm is comprehended by HFASDs
      children as well as by TD children despite being evaluated as highly
      unconventional. This contradiction is discussed from a self-in-relation-to-other
      perspective. We postulate that a new explanation of disabilities of figurative
      language comprehension in children with HFASDs is needed instead of relying on a
      single cognitive process. 

PMID- 24288608
TI  - Cognitive training for schizophrenia in developing countries: a pilot trial in
      Brazil.
AB  - Cognitive deficits in schizophrenia can massively impact functionality and
      quality of life, furthering the importance of cognitive training. Despite the
      development of the field in Europe and in the United States, no programmes have
      been developed and tested in developing countries. Different cultural
      backgrounds, budget restrictions, and other difficulties may render treatment
      packages created in high income countries difficult for adoption by developing
      nations. We performed a pilot double-blind, randomized, controlled trial in order
      to investigate the efficacy and feasibility of an attention and memory training
      programme specially created in a developing nation. The intervention used simple,
      widely available materials, required minimal infrastructure, and was conducted in
      groups. The sample included seventeen stable Brazilians with schizophrenia.
      Sessions were conducted weekly during five months. The cognitive training group
      showed significant improvements in inhibitory control and set-shifting over time.
      Both groups showed improvements in symptoms, processing speed, selective
      attention, executive function, and long-term visual memory. Improvements were
      found in the control group in long-term verbal memory and concentration. Our
      findings reinforce the idea that cognitive training in schizophrenia can be
      constructed using simple resources and infrastructure, facilitating its adoption
      by developing countries, and it may improve cognition. 

PMID- 24288609
TI  - Satisfaction with Life of Schizophrenia Outpatients and Their Caregivers:
      Differences between Patients with and without Self-Reported Sleep Complaints.
AB  - Patients with schizophrenia often present sleep complaints, but its relationship
      with general satisfaction with life (SWL) and burden for caregivers has been
      understudied. We aimed to assess the differences in SWL between patients with and
      without self-reported sleep disturbances and that of their caregivers. In a
      noninterventional study, 811 schizophrenia adult outpatients were screened for
      their subjective perception of having (or not) sleep disturbances and evaluated
      with the Brief Psychiatric Rating Scale (BPRS) and the Pittsburgh Sleep Quality
      Index (PSQI). Patients self-reporting sleep disturbances were significantly more
      symptomatic (P < 0.001), presented significantly worse family support (P =
      0.0236), and self-reported worse SWL in all domains. Caregivers of patients with
      schizophrenia self-reporting sleep disturbances also reported worse SWL in all
      domains, as compared to caregivers of patients without subjective sleep
      disturbances. Patient and caregivers' SWL was significantly correlated to
      patients' quality of sleep (P < 0.0001 for all domains). Patient' and caregivers'
      SWL was negatively affected by patients' poor quality of sleep. We found that
      patients self-reporting sleep disturbances showed greater symptom severity, worse
      quality of sleep, worse SWL, and less caregiver support. SWL was also worse for
      caregivers of patients with schizophrenia reporting sleep disturbances. 

PMID- 24288610
TI  - The transcriptomics of secondary growth and wood formation in conifers.
AB  - In the last years, forestry scientists have adapted genomics and next-generation
      sequencing (NGS) technologies to the search for candidate genes related to the
      transcriptomics of secondary growth and wood formation in several tree species.
      Gymnosperms, in particular, the conifers, are ecologically and economically
      important, namely, for the production of wood and other forestry end products.
      Until very recently, no whole genome sequencing of a conifer genome was
      available. Due to the gradual improvement of the NGS technologies and inherent
      bioinformatics tools, two draft assemblies of the whole genomes sequence of Picea
      abies and Picea glauca arose in the current year. These draft genome assemblies
      will bring new insights about the structure, content, and evolution of the
      conifer genomes. Furthermore, new directions in the forestry, breeding and
      research of conifers will be discussed in the following. The identification of
      genes associated with the xylem transcriptome and the knowledge of their
      regulatory mechanisms will provide less time-consuming breeding cycles and a high
      accuracy for the selection of traits related to wood production and quality. 

PMID- 24288611
TI  - Communication and the emergence of collective behavior in living organisms: a
      quantum approach.
AB  - Intermolecular interactions within living organisms have been found to occur not
      as individual independent events but as a part of a collective array of
      interconnected events. The problem of the emergence of this collective dynamics
      and of the correlated biocommunication therefore arises. In the present paper we
      review the proposals given within the paradigm of modern molecular biology and
      those given by some holistic approaches to biology. In recent times, the
      collective behavior of ensembles of microscopic units (atoms/molecules) has been
      addressed in the conceptual framework of Quantum Field Theory. The possibility of
      producing physical states where all the components of the ensemble move in unison
      has been recognized. In such cases, electromagnetic fields trapped within the
      ensemble appear. In the present paper we present a scheme based on Quantum Field
      Theory where molecules are able to move in phase-correlated unison among them and
      with a self-produced electromagnetic field. Experimental corroboration of this
      scheme is presented. Some consequences for future biological developments are
      discussed. 

PMID- 24288612
TI  - Impact of endothelial microparticles on coagulation, inflammation, and
      angiogenesis in age-related vascular diseases.
AB  - Endothelial microparticles (EMPs) are complex vesicular structures that originate
      from plasma membranes of activated or apoptotic endothelial cells. EMPs play a
      significant role in vascular function by altering the processes of inflammation,
      coagulation, and angiogenesis, and they are key players in the pathogenesis of
      several vascular diseases. Circulating EMPs are increased in many age-related
      vascular diseases such as coronary artery disease, peripheral vascular disease,
      cerebral ischemia, and congestive heart failure. Their elevation in plasma has
      been considered as both a biomarker and bioactive effector of vascular damage and
      a target for vascular diseases. This review focuses on the pleiotropic roles of
      EMPs and the mechanisms that trigger their formation, particularly the
      involvement of decreased estrogen levels, thrombin, and PAI-1 as major factors
      that induce EMPs in age-related vascular diseases. 

PMID- 24288614
TI  - Open and arthroscopic surgical anatomy of the ankle.
AB  - Ankle-related complaints are among the most commonly encountered problems for
      musculoskeletal clinicians. Ankle pathology is widely variable, including, but
      not limited to, fractures, deformity, infection, oncologic diseases,
      neuromuscular conditions, and arthritis. While nonoperative management with
      activity modification, bracing and/or shoe modifications, and medications is
      usually indicated as first line of treatment, surgical intervention may become
      necessary. A thorough understanding of the complex anatomy and biomechanics of
      the ankle, and in particular, the potential neurovascular structures that may be
      encountered, is important to reduce complications and obtain good surgical
      outcomes. The purpose of this review is to discuss the most common open and
      arthroscopic exposures to the ankle with a focus on surgically relevant anatomy
      for each approach. 

PMID- 24288613
TI  - The Contribution of Resting State Networks to the Study of Cortical
      Reorganization in MS.
AB  - Resting State fMRI (RS-fMRI) represents an emerging and powerful tool to explore
      brain functional connectivity (FC) changes associated with neurologic disorders.
      Compared to activation/task-related fMRI, RS-fMRI has the advantages that (i)
      BOLD fMRI signals are self-generated and independent of subject's performance
      during the task and (ii) a single dataset is sufficient to extract a set of RS
      networks (RSNs) that allows to explore whole brain FC. According to these
      features RS-fMRI appears particularly suitable for the study of FC changes
      related to multiple sclerosis (MS). In the present review we will first give a
      brief description of RS-fMRI methodology and then an overview of most relevant
      studies conducted so far in MS by using this approach. The most interesting
      results, in particular, regard the default-mode network (DMN), whose FC changes
      have been correlated with cognitive status of MS patients, and the visual RSN (V
      RSN) whose FC changes have been correlated with visual recovery after optic
      neuritis. The executive control network (ECN), the lateralized frontoparietal
      network (FPN), and the sensory motor network (SMN) have also been investigated in
      MS, showing significant FC rearrangements. All together, RS-fMRI studies
      conducted so far in MS suggest that prominent RS-FC changes can be detected in
      many RSNs and correlate with clinical and/or structural MRI measures. Future RS
      fMRI studies will further clarify the dynamics and clinical impact of RSNs
      changes in MS. 

PMID- 24288615
TI  - Inhibition of Angiogenesis In Vitro by Chebulagic Acid: A COX-LOX Dual Inhibitor.
AB  - Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is
      regulated by several endogenous factors which may stimulate or inhibit the new
      blood vessel growth. Besides these endogenous factors, several exogenous factors
      including some natural compounds are known to modulate angiogenesis. Angiogenesis
      being a potential target for drugs against a number of pathological conditions,
      search for compounds from natural sources that can affect angiogenesis is of
      great interest. The objective of our present study was to understand the effect
      of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of
      Terminalia chebula Retz., on angiogenesis. The model systems used were rat aortic
      rings and human umbilical vein endothelial cells. The results showed that
      chebulagic acid exerts an antiangiogenic effect. This was evidenced from
      decreased sprouting in rat aortic rings and decrease in biochemical markers in
      endothelial cells treated with chebulagic acid. It downregulated the production
      of CD31, E-selectin, and vascular endothelial growth factor in human umbilical
      vein endothelial cells in culture (HUVEC). Further studies to understand the
      molecular mechanism of action of chebulagic acid revealed that CA exerts its anti
      angiogenic effect by modulating VE cadherin-beta catenin signalling in human
      umbilical vein endothelial cells. 

PMID- 24288616
TI  - Assessment of a low-cost ultrasound pericardiocentesis model.
AB  - Introduction. The use of ultrasound during resuscitation is emphasized in the
      latest European resuscitation council guidelines of 2013 to identify treatable
      conditions such as pericardial tamponade. The recommended standard treatment of
      tamponade in various guidelines is pericardiocentesis. As ultrasound guidance
      lowers the complication rates and increases the patient's safety,
      pericardiocentesis should be performed under ultrasound guidance. Acute care
      physicians actually need to train emergency pericardiocentesis. Methods. We
      describe in detail a pericardiocentesis ultrasound model, using materials at a
      cost of about 60 euros. During training courses of focused echocardiography n =
      67, participants tested the phantom and completed a 16-item questionnaire,
      assessing the model using a visual analogue scale (VAS). Results. Eleven of
      fourteen questions were answered with a mean VAS score higher than 60% and thus
      regarded as showing the strengths of the model. Unrealistically outer appearance
      and heart shape were rated as weakness of the model. A total mean VAS score of
      all questions of 63% showed that participants gained confidence for further
      interventions. Conclusions. Our low-cost pericardiocentesis model, which can be
      easily constructed, may serve as an effective training tool of ultrasound-guided
      pericardiocentesis for acute and critical care physicians. 

PMID- 24288617
TI  - Comparison of GlideScope Videolaryngoscopy to Direct Laryngoscopy for Intubation
      of a Pediatric Simulator by Novice Physicians.
AB  - Objective. To compare novice clinicians' performance using GlideScope
      videolaryngoscopy (GVL) to direct laryngoscopy (DL). Methods. This was a
      prospective, randomized crossover study. Incoming pediatric interns intubated
      pediatric simulators in four normal and difficult airway scenarios with GVL and
      DL. Primary outcomes included time to intubation and rate of successful
      intubation. Interns rated their satisfaction of the devices and chose the
      preferred device. Results. Twenty-five interns were included. In the normal
      airway scenario, there were no differences in mean time for intubation with GVL
      or DL (61.4 versus 67.4 seconds, P = NS) or number of successful intubations (19
      versus 18, P = NS). In the difficult airway scenario, interns took longer to
      intubate with GVL than DL (87.7 versus 61.3 seconds, P = 0.018), but there were
      no differences in successful intubations (14 versus 15, P = NS). There was a
      trend towards higher satisfaction for GVL than DL (7.3 versus 6.4, P = NS), and
      GVL was chosen as the preferred device by a majority of interns (17/25, 68%).
      Conclusions. For novice clinicians, GVL does not improve time to intubation or
      intubation success rates in a pediatric simulator model of normal and difficult
      airway scenarios. Still, these novice clinicians overall preferred GVL. 

PMID- 24288618
TI  - Rapid infusion rituximab for maintenance therapy: is it feasible?
AB  - Rituximab is an anti-CD-20 monoclonal antibody used in the management of
      lymphoproliferative disorders. The use of maintenance rituximab has improved
      progression free survival and overall survival in follicular lymphomas. Although
      rapid rituximab infusions have been studied extensively, there is little data on
      the use of rapid infusions during maintenance therapy for low grade lymphomas.
      The primary objective of this retrospective analysis was to evaluate the
      incidence of Grade 3 and 4 toxicities with maintenance rapid infusion rituximab
      according to the Common Terminology Criteria for Adverse Events version 4 (CTC v.
      4). Secondary objectives included evaluating all grade infusion related adverse
      events and correlation of adverse events with varying schedules of rituximab
      maintenance therapy. All patients who received rapid infusion rituximab as
      maintenance therapy for low grade lymphoma between December 2007 and November
      2011 were included. Rapid rituximab infusions were administered over 90 minutes.
      Demographic, laboratory and clinical data were collected. A total of 109 patients
      received 647 rapid rituximab infusions. Three patients experienced an adverse
      reaction which resulted in one grade 1 infusion reaction and three grade 3
      infusion reactions. No patients required hospitalization. All 3 patients received
      pharmacological and/or supportive care to relieve symptoms associated with the
      reaction. 

PMID- 24288619
TI  - Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in
      Asthmatic Children.
AB  - Rationale. The sleep-related factors that modulate the nocturnal worsening of
      asthma in children are poorly understood. This study addressed the hypothesis
      that asthmatic children have a REM sleep-related vulnerability trait that is
      independent of OSA. Methods. We conducted a retrospective cross-sectional
      analysis of pulse-oximetry signals obtained during REM and NREM sleep in control
      and asthmatic children (n = 134). Asthma classification was based on
      preestablished clinical criteria. Multivariate linear regression model was built
      to control for potential confounders (significance level P <= 0.05). Results. Our
      data demonstrated that (1) baseline nocturnal respiratory parameters were not
      significantly different in asthmatic versus control children, (2) the maximal %
      of SaO2 desaturation during REM, but not during NREM, was significantly higher in
      asthmatic children, and (3) multivariate analysis revealed that the association
      between asthma and REM-related maximal % SaO2 desaturation was independent of
      demographic variables. Conclusion. These results demonstrate that children with
      asthma have a REM-related vulnerability trait that impacts oxygenation
      independently of OSA. Further research is needed to delineate the REM sleep
      neurobiological mechanisms that modulate the phenotypical expression of nocturnal
      asthma in children. 

PMID- 24288620
TI  - Survival and Prognostic Factors for AIDS and Non-AIDS Patients with Non-Hodgkin's
      Lymphoma in Bahia, Brazil: A Retrospective Cohort Study.
AB  - Despite the benefits of HAART, HIV-infected patients are increasingly affected by
      different malignancies. We compared a 5-year-period survival time and prognostic
      factors for HIV-1-infected individuals diagnosed with non-Hodgkin lymphomas (NHL)
      in a nested case-control study, with non-HIV-infected individuals in Salvador,
      Brazil. Survival time and prognostic factors were compared to HIV-negative
      patients. 31 cases (versus 63 controls) had a significantly more advanced NHL at
      diagnosis and lower mean CD4 count (26 cells/mm(3)) than controls. Mean overall
      survival (OS) was 35.8 versus 75.4 months, for cases and controls, respectively
      (P < 0.001), while mean event-free survival time (EFS) was 34.5 months for cases,
      versus 68.8 for controls (P = 0.002). Higher IPI, increased LDH levels, bone
      marrow infiltration, lower absolute lymphocyte counts (<1,000 cells/mm(3)), and
      type B symptoms were associated with a shorter survival time for cases. Although
      patients without poorer prognostic factors at baseline had an OS comparable to
      controls, the mean CD4 cell count for cases was similar for patients with
      favorable and nonfavorable response to therapy. Our findings suggest that HIV-1
      infection is significantly associated with a shorter survival time for patients
      with NHL, independently of other predictive factors and of disease stage. 

PMID- 24288621
TI  - An evaluation of the effects of the transobturator tape procedure on sexual
      satisfaction in women with stress urinary incontinence using the libido scoring
      system.
AB  - Introduction and Hypothesis. Most women experience automatic urine leakage in
      their lifetimes. SUI is the most common type in women. Suburethral slings have
      become a standard surgical procedure for the treatment of stress urinary
      incontinence when conservative therapy failed. The treatment of stress urinary
      incontinence by suburethral sling may improve body image by reducing urinary
      leakage and may improve sexual satisfaction. Methods. A total of 59 sexually
      active patients were included in the study and underwent a TOT outside-in
      procedure. The LSS was applied in all patients by self-completion of
      questionnaires preoperatively and 6 months after the operation. General pleasure
      with the operation was measured by visual analogue score (VAS). Pre- and
      postoperative scores were recorded and analyzed using SPSS 11.5. Results. Two
      parameters of the LSS, orgasm and who starts the sexual activity, increased at a
      statistically significant rate. Conclusion. Sexual satisfaction and desire have
      partially improved after the TOT procedure. 

PMID- 24288622
TI  - The afferent visual pathway: designing a structural-functional paradigm of
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a disease of the central nervous system (CNS) believed
      to arise from a dysfunctional immune-mediated response in a genetically
      susceptible host. The actual cause of MS is not known, and there is ongoing
      debate about whether this CNS disorder is predominantly an inflammatory versus a
      degenerative condition. The afferent visual pathway (AVP) is frequently involved
      in MS, such that one in every five individuals affected presents with acute optic
      neuritis (ON). As a functionally eloquent system, the AVP is amenable to
      interrogation with highly reliable and reproducible tests that can be used to
      define a structural-functional paradigm of CNS injury. The AVP has numerous
      unique advantages as a clinical model of MS. In this review, the parameters and
      merits of the AVP model are highlighted. Moreover, the roles the AVP model may
      play in elucidating mechanisms of brain injury and repair in MS are described. 

PMID- 24288623
TI  - Profile of cognitive complaints in vascular mild cognitive impairment and mild
      cognitive impairment.
AB  - Objective. Vascular mild cognitive impairment (VaMCI) is differentiated from mild
      cognitive impairment (MCI) by the presence of vascular events such as stroke or
      small vessel disease. Typically, MCI and VaMCI patients present with subjective
      complaints regarding cognition; however, little is known about the specific
      nature of these complaints. We aimed to create a profile of subjective cognitive
      complaints in MCI and VaMCI patients with similar levels of objective cognitive
      performance. Methods. Twenty MCI and twenty VaMCI patients were recruited from a
      Memory Disorders Clinic in Toronto. Subjective cognitive complaints were assessed
      and categorized using the Neuropsychological Impairment Scale. Results. MCI and
      VaMCI patients achieved similar scores on measures of objective cognitive
      function (P > 0.100). However, the VaMCI group had more subjective complaints
      than the MCI group (P = 0.050), particularly in the critical items, cognitive
      efficiency, memory, and verbal learning domains of the Neuropsychological
      Impairment Scale. Conclusions. Our findings support the idea that VaMCI and MCI
      differ in their clinical profiles, independent of neuroimaging. VaMCI patients
      have significantly more subjective cognitive complaints and may be exhibiting
      particular deficits in memory, verbal learning, and cognitive efficiency. Our
      findings promote the need for further research into VaMCI-specific cognitive
      deficits. 

PMID- 24288624
TI  - The plasma membrane Ca2+-ATPase2 (PMCA2) is involved in the regulation of
      Purkinje cell dendritic growth in cerebellar organotypic slice cultures.
AB  - Purkinje cells are the principal neurons of the cerebellar cortex and have an
      extensive and elaborate dendritic tree. Chronic activation of type I metabotropic
      glutamate receptors inhibits Purkinje cell dendritic growth in organotypic
      cerebellar slice cultures. This effect is mediated by calcium influx through P/Q
      type and T-type Ca(2+) channels. We have now studied the role of the plasma
      membrane Ca(2+)-ATPase2 (PMCA2), a major calcium extrusion pump, for Purkinje
      cell dendritic development. We found that PMCA2 is strongly expressed in the
      plasma membrane and dendritic spines of Purkinje cells in organotypic slice
      cultures compatible with a role for controlling the local dendritic calcium
      equilibrium. Inhibition of PMCA2 activity by carboxyeosin resulted in a moderate
      reduction of Purkinje cell dendritic tree size indicating that the extrusion of
      calcium by PMCA2 is important for maintaining the dendritic calcium concentration
      and controlling dendritic growth. When inhibition of PMCA2 was combined with
      stimulation of type I metabotropic glutamate receptors, it partially rescued
      dendritic morphology. This protection can be explained by a compensatory
      inactivation of voltage-gated calcium channels in Purkinje cells after PMCA2
      inhibition. Our results demonstrate that PMCA2 activity is an important regulator
      of the dendritic calcium equilibrium controlling Purkinje cell dendritic growth. 

PMID- 24288625
TI  - Cross-modal plasticity results in increased inhibition in primary auditory
      cortical areas.
AB  - Loss of sensory input from peripheral organ damage, sensory deprivation, or brain
      damage can result in adaptive or maladaptive changes in sensory cortex. In
      previous research, we found that auditory cortical tuning and tonotopy were
      impaired by cross-modal invasion of visual inputs. Sensory deprivation is
      typically associated with a loss of inhibition. To determine whether inhibitory
      plasticity is responsible for this process, we measured pre- and postsynaptic
      changes in inhibitory connectivity in ferret auditory cortex (AC) after cross
      modal plasticity. We found that blocking GABAA receptors increased responsiveness
      and broadened sound frequency tuning in the cross-modal group more than in the
      normal group. Furthermore, expression levels of glutamic acid decarboxylase (GAD)
      protein were increased in the cross-modal group. We also found that blocking
      inhibition unmasked visual responses of some auditory neurons in cross-modal AC.
      Overall, our data suggest a role for increased inhibition in reducing the
      effectiveness of the abnormal visual inputs and argue that decreased inhibition
      is not responsible for compromised auditory cortical function after cross-modal
      invasion. Our findings imply that inhibitory plasticity may play a role in
      reorganizing sensory cortex after cross-modal invasion, suggesting clinical
      strategies for recovery after brain injury or sensory deprivation. 

PMID- 24288626
TI  - Microglial ion channels as potential targets for neuroprotection in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a chronic, degenerative neurological disorder that is
      estimated to affect at least 1 million individuals in the USA and over 10 million
      worldwide. It is thought that the loss of neurons and development of inclusion
      bodies occur gradually over decades until they progress to the point where ~60%
      of the dopamine neurons are lost and patients present with motor dysfunction. At
      present, it is not clear what causes this progression, and there are no current
      therapies that have been successful in preventing PD progression. Although there
      are many hypotheses regarding the mechanism of PD progression, neuroinflammation
      may be a major contributor to PD pathogenesis. Indeed, activated microglia and
      subsequent neuroinflammation have been consistently associated with the
      pathogenesis of PD. Thus, interference with this process could provide a means of
      neuroprotection in PD. This review will discuss the potential of targeting
      microglia to reduce neuroinflammation in PD. Further, we discuss the potential of
      microglial ion channels to serve as novel targets for neuroprotection in PD. 

PMID- 24288628
TI  - Phaeochromocytoma crisis: two cases of undiagnosed phaeochromocytoma presenting
      after elective nonrelated surgical procedures.
AB  - Phaeochromocytoma is a catecholamine producing tumour and an uncommon cause of
      hypertension. We present two cases of relatively asymptomatic individuals, in
      which previously undiagnosed phaeochromocytoma was unmasked by elective
      nonadrenal surgical procedures, manifesting as postoperative hypertensive crisis
      and subsequent cardiogenic shock. The initial management in intensive care is
      discussed, in addition to the clinical and biochemical diagnostic challenges
      present. Successful adrenalectomy was performed in each case. 

PMID- 24288627
TI  - Managing inflammation after spinal cord injury through manipulation of macrophage
      function.
AB  - Spinal cord injury (SCI) triggers inflammation with activation of innate immune
      responses that contribute to secondary injury including oligodendrocyte
      apoptosis, demyelination, axonal degeneration, and neuronal death. Macrophage
      activation, accumulation, and persistent inflammation occur in SCI. Macrophages
      are heterogeneous cells with extensive functional plasticity and have the
      capacity to switch phenotypes by factors present in the inflammatory
      microenvironment of the injured spinal cord. This review will discuss the role of
      different polarized macrophages and the potential effect of macrophage-based
      therapies for SCI. 

PMID- 24288629
TI  - Iatrogenic Left Main Bronchus Injury following Atraumatic Double Lumen
      Endotracheal Tube Placement.
AB  - Tracheobronchial disruption is an uncommon but severe complication of double
      lumen endotracheal tube placement. The physical properties of a double lumen tube
      (large external diameter and length) make tracheobronchial injury more common
      than that associated with smaller single lumen endotracheal tubes. Here we
      present the case of an iatrogenic left main bronchus injury caused by placement
      of a double lumen tube in an otherwise unremarkable airway. 

PMID- 24288630
TI  - Hutchinson-gilford progeria syndrome: a rare genetic disorder.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare pediatric genetic syndrome
      with incidence of one per eight million live births. The disorder is
      characterised by premature aging, generally leading to death at approximately
      13.4 years of age. This is a follow-up study of a 9-year-old male with clinical
      and radiographic features highly suggestive of HGPS and presented here with
      description of differential diagnosis and dental consideration. This is the first
      case report of HGPS which showed pectus carinatum structure of chest. 

PMID- 24288631
TI  - Intraoral adult rhabdomyoma: a case report.
AB  - A case of adult rhabdomyoma is reported. The lesion is a rare benign tumor of
      skeletal muscle origin which occurs predominantly in the head and neck region. In
      the present case, the clinical diagnosis favored a benign salivary gland tumor.
      Histologically, the tumor was composed of large round, oval, and polygonal cells
      of varying size with abundant pale, eosinophilic, fine, granular cytoplasm with
      peripherally located nuclei. Immunohistochemically, the lesion was positive for
      muscle-specific actin, smooth muscle actin, desmin, S100 protein, and Masson's
      trichrome. Electron microscopic examination confirmed the presence of numerous
      myofibrils. The lesion was treated by surgical resection. The clinical,
      histological, immunohistochemical, and ultrastructural features are discussed in
      this study. 

PMID- 24288632
TI  - Mixed medullary-follicular carcinoma of the thyroid.
AB  - Introduction. Mixed medullary-follicular thyroid carcinoma is an uncommon tumor
      that consists of both follicular and parafollicular cells. Case. We report a 43
      year-old woman with a palpable mass in the right side of the neck. Fine needle
      aspiration suggested a diagnosis of high grade anaplastic carcinoma that has been
      associated with papillary features. Total thyroidectomy was done in which
      histopathological examination showed diagnosis of medullary carcinoma.
      Immunohistochemical staining was positive for chromogranin, calcitonin, and
      thyroglobulin in tumoral cells. Conclusion. Mixed medullary-follicular thyroid
      carcinoma is a rare tumor. Diagnosis of these tumors with fine needle aspiration
      is very difficult and may lead to misdiagnosis. It is necessary to correlate the
      cytological finding with serum calcitonin and thyroglobulin. Also immunostaining
      for calcitonin and thyroglobulin confirms diagnosis. 

PMID- 24288633
TI  - Monitoring Patient Improvement Parameters following Pasireotide Treatment in
      Cushing's Disease.
AB  - Cushing's disease (CD) is a disorder in which chronic excess adrenocorticotropic
      hormone production is associated with multiple comorbidities and diminished
      quality of life. Postsurgical monitoring is important, and newer therapies are
      available for the management of surgical failure or disease recurrence. In this
      clinical case, we illustrate the importance of the nursing role in long-term
      management of CD, particularly as nurses may be the first point of contact for
      patients with CD. Alertness to disease signs and symptoms is crucial for timely
      diagnosis and improved outcomes. Successful therapy for CD requires careful
      monitoring of hormonal control, metabolic parameters, and therapy complications.
      Ongoing management requires lifelong monitoring of metabolic parameters, of side
      effects of treatment, and of signs of disease recurrence. Appropriate referrals
      may be required to facilitate overall outcomes and patient wellbeing. This
      patient was enrolled in a Phase III trial that was registered in the USA with
      clinicaltrial.gov. 

PMID- 24288634
TI  - Extensive growth of an anaplastic meningioma.
AB  - We present the case of a 30-year-old male patient with an almost complete
      destruction of the calvarial bone through an anaplastic meningioma diagnosed in
      line with dizziness. Neuroimaging revealed an extensive growing, contrast
      enhancing lesion expanding at the supra- and infratentorial convexity,
      infiltrating and destroying large parts of the skull, and infiltrating the skin.
      Due to progressive ataxia and dysarthria with proven tumor growth in the
      posterior fossa in the continuing course, parts of the tumor were resected. A
      surgical procedure with the aim of complete tumor resection in a curative manner
      was not possible. Six months after the first operation, due to a new tumor
      progression, most extensive tumor resection was performed. Due to the aggressive
      and destructive growth with a high rate of recurrence and tendency of metastases,
      anaplastic meningiomas can be termed as malignant tumors. The extrinsic growth
      masks the tumor until they reach a size, which makes these tumors almost
      unresectable. In the best case scenarios, the five-year survival is about 50%.
      With the presented case, we would like to show the aggressive behavior of
      anaplastic meningiomas in a very illustrative way. Chemotherapy, radiotherapy,
      and surgery reach their limits in this tumor entity. 

PMID- 24288635
TI  - Bilateral ectopic hypoplastic uteri attached to bilateral pelvic sidewalls in a
      21-year-old patient with primary amenorrhea: the first published report.
AB  - Mullerian duct anomalies (MDAs) encompass a group of anatomical malformations
      resulting from defective development, fusion, migration, or resorption of
      Mullerian (paramesonephric) ducts during embryonic life. Herein, we report the
      first case of an exceedingly uncommon MDA (bilateral ectopic hypoplastic uteri
      attached to bilateral pelvic sidewalls) in a 21-year-old woman who was referred
      to our tertiary care center as a case of primary amenorrhea for workup and
      further management. 

PMID- 24288636
TI  - Renal leiomyosarcoma: a diagnostic challenge.
AB  - Renal leiomyosarcoma is a very rare tumor that clinically and radiographically
      mimics more common renal malignancies. The infrequency of the condition makes it
      very difficult to diagnose. A 70-year-old male smoker presented with months of
      hematuria, right-sided flank pain, and weight loss. Imaging revealed a 3.8
      centimeter renal mass that had characteristics similar to renal cell carcinoma.
      Initial biopsy of the mass was negative for malignancy. Two months later,
      subsequent imaging revealed what appeared to be metastatic bone lesions. Again, a
      biopsy of one of the lesions was negative for malignancy. Subsequent ureteral
      pyeloscopy, ureteroscopic renal pelvis biopsy, and brush cytology were negative
      for malignancy as well. The decision was made to perform nephrectomy for the
      removal of the mass. Pathologic analysis revealed renal leiomyosarcoma. This case
      illustrates the difficulty in diagnosing renal leiomyosarcoma. Repeated
      pathologic sampling was negative because of the tumor heterogeneity. Prompt
      diagnosis and treatment are very significant as surgical resection at an early
      stage offers the best prognosis. 

PMID- 24288637
TI  - Canthaxanthin retinopathy with visual loss: a case report and review.
AB  - Canthaxanthin is a naturally occurring chemical, which is most commonly utilized
      as a colorant for food and dyes or a skin bronzing agent. Its most prevalent
      impact on human health is canthaxanthin retinopathy, which appears as
      birefringent, yellow to red crystals surrounding the macula. This occurs with
      increasing, dose-dependent exposure. Generally, patients remain asymptomatic and
      findings may only be evident on funduscopic examination. Cessation of
      canthaxanthin ingestion appears to reverse the retinopathy, but the time until
      crystal disappearance is variable. Despite a usually favorable outcome, long
      standing visual changes may occur. We report a case of an 84-year-old woman with
      significant visual loss secondary to canthaxanthin retinopathy that ultimately
      improved upon cessation of the drug. 

PMID- 24288638
TI  - Gas gangrene in orthopaedic patients.
AB  - Clostridial myonecrosis is most often seen in settings of trauma, surgery,
      malignancy, and other underlying immunocompromised conditions. Since 1953 cases
      of gas gangrene have been reported in orthopaedic patients including open
      fractures, closed fractures, and orthopaedic surgeries. We present a case of 55
      year-old obese woman who developed rapidly progressive gas gangrene in her right
      leg accompanied by tibial plateau fracture without skin lacerations. She was
      diagnosed with clostridial myonecrosis and above-the-knee amputation was carried
      out. This patient made full recovery within three weeks of the initial episode.
      We identified a total of 50 cases of gas gangrene in orthopaedic patients.
      Several factors, if available, were analyzed for each case: age, cause of injury,
      fracture location, pathogen, and outcome. Based on our case report and the
      literature review, emergency clinicians should be aware of this severe and
      potentially fatal infectious disease and should not delay treatment or prompt
      orthopedic surgery consultation. 

PMID- 24288639
TI  - Recurrent vocal fold paralysis and parsonage-turner syndrome.
AB  - Background. Parsonage-Turner syndrome, or neuralgic amyotrophy (NA), is an acute
      brachial plexus neuritis that typically presents with unilateral shoulder pain
      and amyotrophy but also can affect other peripheral nerves, including the
      recurrent laryngeal nerve. Idiopathic vocal fold paralysis (VFP) represents
      approximately 12% of the VFP cases and recurrence is extremely rare. Methods and
      Results. We report a man with isolated recurrent unilateral right VFP and a
      diagnosis of NA years before. Conclusions. We emphasize that shoulder pain and
      amyotrophy should be inquired in any patient suffering from inexplicable
      dysphonia, and Parsonage-Turner syndrome should be considered in the differential
      diagnosis of idiopathic VFP. 

PMID- 24288640
TI  - Spontaneous bilateral meningoencephalocoeles of the temporal bones.
AB  - Spontaneous tegmen tympani defects are rare with even rarer bilateral cases. The
      symptoms are nonspecific; hence, a high index of suspicion is required to prevent
      serious intracranial complications. We present a case of spontaneous bilateral
      tegmen tympani defects with associated meningoencephalocoeles in a 54-year-old
      male who presented with the signs and symptoms of severe meningitis. After
      careful workup which included a lumbar puncture, CT and MRI scans, both defects
      were repaired using a middle fossa approach. The patient made an uneventful
      recovery with complete cessation of otorrhoea and improvement in his hearing. 

PMID- 24288641
TI  - An unusual case of rapidly progressive hyperbilirubinemia.
AB  - We present an unusual case of hyperbilirubinemia with rapid early progression
      leading to bilirubin encephalopathy in a term neonate. Despite early recognition
      and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL
      at 32 hours of life. Prior to an emergent exchange transfusion, the patient's
      diagnostic evaluation was significant for Coombs-negative microangiopathic
      hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of
      ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding
      diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman
      syndrome. This rare disease is often misdiagnosed, especially in the newborn
      period. 

PMID- 24288642
TI  - Complications of bezoar in children: what is new?
AB  - A bezoar is a mass found trapped in the gastrointestinal system. The condition
      may be associated with pica, especially in developmentally retarded children.
      Clinical manifestations are usually nonspecific. Endoscopic diagnosis and removal
      of the foreign materials is often indicated. Occasionally, severe complications
      may occur. We report two cases to illustrate the clinical features and
      complications in these children. In the first case, a reliable history was not
      obtained in the developmentally delayed girl which precluded prompt diagnosis,
      but the grossly dilated stomach on plain abdominal radiograph gave clues to an
      underlying insidious mechanical obstruction of upper gastrointestinal tract. In
      the second case of a normal child, the unrelenting symptoms and weight loss
      prompt further investigations which revealed the diagnosis. Literature on
      pediatric bezoar is reviewed. Oesophagoduodenoscopy is the investigation of
      choice for diagnostic confirmation, but surgical facilities must be available to
      deal with acute complications. 

PMID- 24288643
TI  - Foot Skin Ischemic Necrosis following Heel Prick in a Newborn.
AB  - There are only a few reports on side effects after heel prick in neonates
      although heel prick has been performed all over the world for many years. The
      medicine staff had obtained only a drop of blood by pricking the baby's heel
      using a lancet without compressing the heel or foot to measure his blood glucose
      level 3 hours after birth. However he developed a severe and hemorrhagic skin
      reaction on his entire left foot, beginning 30 minutes after obtaining the drop
      of blood by pricking the baby's heel using a lancet. The lesion, which was
      treated with topical mupirocin and povidone-iodine solution daily, slowly
      decreased in size and had almost fully resolved within 3 weeks. He was healthy
      and 9 months old at the time of writing this paper. We herein report a case of
      foot skin ischemic necrosis following heel prick in a newborn. To our knowledge
      this patient is the first case of foot skin ischemic necrosis due to heel prick
      in newborns. 

PMID- 24288644
TI  - Lymphoepithelioma-like carcinoma of the lung: an unusual case and literature
      review.
AB  - We described a case of lymphoepithelioma-like carcinoma (LELC) of the lung of a
      65-year-old man with initial symptoms of intermittent chest pain and mild
      shortness of breath for 2 weeks. A right-lung mass was noted on chest computed
      tomography (CT) scan and was proved histopathologically as LELC of lung after
      video-assisted thorascopic lobectomy. He was successfully treated with lobectomy
      with postoperative adjuvant chemotherapy and is alive without signs of recurrence
      for 36 months after the diagnosis. It is important for clinicians, pathologists,
      and radiologists to understand the clinical, pathological, and radiological
      presentations of this neoplasm to avoid improper clinical decision making and
      misdiagnosis. 

PMID- 24288645
TI  - Small Bowel Perforation due to Gossypiboma Caused Acute Abdomen.
AB  - Gossypiboma, an infrequent surgical complication, is a mass lesion due to a
      retained surgical sponge surrounded by foreign body reaction. In this case
      report, we describe gossypiboma in the abdominal cavity which was detected 14
      months after the hysterectomy due to acute abdominal pain. Gossypiboma was
      diagnosed by computed tomography (CT). The CT findings were a rounded mass with a
      dense central part and an enhancing wall. In explorative laparotomy, small bowel
      loops were seen to be perforated due to inflammation of long standing
      gossypiboma. Jejunal resection with end-to-end anastomosis was performed. The
      patient was discharged whithout complication. This case was presented to point to
      retained foreign body (RFB) complications and we believed that the possibility of
      a retained foreign body should be considered in the differential diagnosis of who
      had previous surgery and complained of pain, infection, or palpable mass. 

PMID- 24288646
TI  - Successful removal of metal objects causing penile strangulation by a silk
      winding method.
AB  - Penile strangulation is a challenge to urologists. The decompression of the penis
      is required to prevent long-term complications. Metal objects are difficult to
      remove. Cutting is the most common method described. Appropriate cutting tools
      may be difficult to obtain, and the process may be time-consuming with the
      possibility of iatrogenic penile injury. In this paper, we will present a simple
      method to remove such objects by use a silk winding method and subcutaneous
      puncture. 

PMID- 24288647
TI  - Bilateral synchronous granulomatous orchitis in a patient with erectile
      disfunction: clinical and pathologic study of the case.
AB  - A 50-year-old male patient presented with erectile failure and loss of libido. In
      the physical examination, there were stone-hard indurations in his bilateral
      testes. The ultrasonographic study demonstrated multiple hypoechoic areas in the
      testes and normal epididymis. Since the lesion was presumed as malignancy,
      bilateral inguinal exploration was performed and intraoperative frozen biopsies
      were studied and diagnosed as inflammatory process. Nevertheless, we decided to
      perform left orchiectomy to a deeper histopathologic analysis which revealed
      granulomatous orchitis, mastocytosis, and severe depletion of Leydig cells at the
      testicular interstitium. Differential diagnosis between testicular tumor and
      granulomatous orchitis is very difficult in any examination except by
      histological findings. Bilateral cases of this pathology are relatively rare, but
      it is necessary to distinguish them from the testicular tumor before surgical
      intervention to avoid an unnecessary orchiectomy. 

PMID- 24288648
TI  - Tumor seeding of percutaneous nephrostomy tract from urothelial carcinoma of the
      kidney.
AB  - Urothelial carcinoma (UC) of the renal pelvis has been rarely shown to
      metastasize to the skin. Tumor seeding from iatrogenic procedures is a source of
      spreading of UC to the skin. We herein present a case of primary UC of the renal
      pelvis with spreading to the skin from a percutaneous nephrostomy tract. 

PMID- 24288649
TI  - Distribution and antimicrobial susceptibility pattern of bacterial pathogens
      causing urinary tract infection in urban community of meerut city, India.
AB  - Urinary tract infection is one of the common infections in the Indian community.
      Distribution and susceptibility of UTI-causing pathogens change according to time
      and place. This study was conducted to determine the distribution and
      antimicrobial susceptibility of uropathogens in the Indian community as well as
      to determine the effect of gender and age on the etiology of bacterial
      uropathogens. Clean catch midstream urine samples were collected from 288
      patients of the age ranging from 15 to >=48 years. Antimicrobial susceptibility
      was performed on all isolated bacteria by Kirby Bauer's disc diffusion method.
      The multiple antibiotic resistance (MAR) index of each antibiotic was calculated.
      The UTI prevalence was 53.82% in patients; however, the prevalence was
      significantly higher in females than in males (females: 73.57%; males: 35.14%; P
      = 0.000). Females within the age group of 26-36 years and elderly males of >=48
      years showed higher prevalence of UTI. Gram negative bacteria (90.32%) were found
      in high prevalence than Gram positive (9.68%). Escherichia coli (42.58%) was the
      most prevalent gram negative isolate. Nitrofurantoin (78.71%) was found the most
      resistant drug among all uropathogens. Tested carbapenems were found the most
      susceptible drug against isolated uropathogens which showed 92.26% and 84.52%
      susceptibility, respectively. 

PMID- 24288650
TI  - Role of copper and cholesterol association in the neurodegenerative process.
AB  - Age is one of the main factors involved in the development of neurological
      illnesses, in particular, Alzheimer, and it is widely held that the rapid aging
      of the world population is accompanied by a rise in the prevalence and incidence
      of Alzheimer disease. However, evidence from recent decades indicates that Cu and
      Cho overload are emerging causative factors in neurodegeneration, a hypothesis
      that has been partially investigated in experimental models. The link between
      these two variables and the onset of Alzheimer disease has opened up interesting
      new possibilities requiring more in-depth analysis. The aim of the present study
      was therefore to investigate the effect of the association of Cu + Cho (CuCho) as
      a possible synergistic factor in the development of an Alzheimer-like pathology
      in Wistar rats. We measured total- and nonceruloplasmin-bound Cu and Cho (free
      and sterified) contents in plasma and brain zones (cortex and hippocampus),
      markers of oxidative stress damage, inflammation, and programmed cell death
      (caspase-3 and calpain isoforms). The ratio beta-amyloid (1-42)/(1-40) was
      determined in plasma and brain as neurodegenerative biomarker. An evaluation of
      visuospatial memory (Barnes maze test) was also performed. The results
      demonstrate the establishment of a prooxidative and proinflammatory environment
      after CuCho treatment, hallmarked by increased TBARS, protein carbonyls, and
      nitrite plus nitrate levels in plasma and brain zones (cortex and hippocampus)
      with a consequent increase in the activity of calpains and no significant changes
      in caspase-3. A simultaneous increase in the plasma A beta 1-42/A beta 1-40 ratio
      was found. Furthermore, a slight but noticeable change in visuospatial memory was
      observed in rats treated with CuCho. We conclude that our model could reflect an
      initial stage of neurodegeneration in which Cu and Cho interact with one another
      to exacerbate neurological damage. 

PMID- 24288651
TI  - Virtual screening and biological evaluation of piperazine derivatives as human
      acetylcholinesterase inhibitors.
AB  - The piperazine derivatives have been shown to inhibit human acetylcholinesterase.
      Virtual screening by molecular docking of piperazine derivatives 1-(1,4
      benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4
      benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4
      benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral
      anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2
      carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4
      benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic
      site or catalytic site with hydrogen bond. All the derivatives have differed in
      number of H-bonds and hydrophobic interactions. The peripheral anionic site
      interacting molecules have proven to be potential therapeutics in inhibiting
      amyloid peptides aggregation in Alzheimer's disease. All the piperazine
      derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4
      benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value. 

PMID- 24288652
TI  - Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the
      Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a
      Recombinant between B and O Alleles.
AB  - The human ABO blood group gene consists of three main alleles (A, B, and O) that
      encode a glycosyltransferase. The A and B alleles differ by two critical amino
      acids in exon 7, and the major O allele has a single nucleotide deletion
      (Delta261) in exon 6. Previous evolutionary studies have revealed that the A
      allele is the most ancient, B allele diverged from the A allele with two critical
      amino acid substitutions in exon 7, and the major O allele diverged from the A
      allele with Delta261 in exon 6. However, a recent phylogenetic network analysis
      study showed that the A allele of humans emerged through a recombination between
      the B and O alleles. In the previous study, a restricted dataset from only two
      populations was used. In this study, therefore, we used a large single nucleotide
      polymorphism (SNP) dataset from the HapMap Project. The results indicated that
      the A101-A201-O09 haplogroup was a recombinant lineage between the B and O
      haplotypes, containing the intact exon 6 from the B allele and the two critical A
      type sites in exon 7 from the major O allele. Its recombination point was assumed
      to be located just behind Delta261 in exon 6. 

PMID- 24288653
TI  - Nanohydroxyapatite application to osteoporosis management.
AB  - Hydroxyapatite is chemically related to the inorganic component of bone matrix as
      a complex structure with the formula of Ca10(OH)2(PO4)6. Previous studies have
      reported the application of microsized hydroxyapatite to bone regeneration, but
      the result is not satisfied. The limitation comes from the size of
      hydroxyapatite. In addition, the duration of treatment is very long. The
      advantages of hydroxyapatite nanocrystal are the osteoconduction, bioresorption,
      and contact in close distance. Crystal in osteoporotic bone is calcium phosphate
      hydroxide with the chemical formula of Ca10(OH)2(PO4)6. Crystal of normal bone is
      sodium calcium hydrogen carbonate phosphate hydrate with the chemical formula of
      Ca8H2(PO4)6 .H2O-NaHCO3-H2O. The recent development is applying nanobiology
      approach to hydroxyapatite. This is based on the concept that the mineral atoms
      arranged in a crystal structure of hydroxyapatite can be substituted or
      incorporated by the other mineral atoms. In conclusion, the basic elements of
      hydroxyapatite crystals, composed of atomic minerals in a certain geometric
      pattern, and their relationship to the bone cell biological activity have opened
      opportunities for hydroxyapatite crystals supplement application on osteoporosis.
      Understanding of the characteristics of bone hydroxyapatite crystals as well as
      the behavior of mineral atom in the substitution will have a better impact on the
      management of osteoporosis. 

PMID- 24288654
TI  - Copper-Catalyzed Carboxylation of Aryl Iodides with Carbon Dioxide.
AB  - A method for carboxylation of aryl iodides with carbon dioxide has been
      developed. The reaction employs low loadings of copper iodide/TMEDA or DMEDA
      catalyst, 1 atm of CO2, DMSO or DMA solvent, and proceeds at 25-70  degrees C.
      Good functional group tolerance is observed, with ester, bromide, chloride,
      fluoride, ether, hydroxy, amino, and ketone functionalities tolerated.
      Additionally, hindered aryl iodides such as iodomesitylene can also be
      carboxylated.

PMID- 24288655
TI  - Fatigue and Sleep Disturbance Related to Perceived Stress in Chinese HIV-Positive
      Individuals: A Mixed Methods Study.
AB  - BACKGROUND: Few studies of HIV+ individuals in China have examined the
      associations between HIV-related stress with sleep disturbance and fatigue, which
      are common complaints among people living with HIV/AIDS (PLWHA). We carried out
      this study to examine the relationships among perceived stress, sleep
      disturbance, and fatigue in PLWHA in China. METHODS: A mixed methods study design
      was used during data collection in Shanghai, China, from December 2009 to March
      2010. Qualitative in-depth interviews were conducted with 19 HIV+ females.
      Additionally, cross-sectional audio computer-assisted self-interviews (ACASI)
      were conducted to collect quantitative data from a convenience sample of 107 HIV+
      patients (84% were male) including the following scales: 1) Perceived Stress
      Scale for PLWHA, 2) General Sleep Disturbance Scale, and 3) Fatigue Scale.
      RESULTS: The major themes that emerged from the in-depth interviews were around
      life stress with HIV, sleep disturbance, and fatigue. Participants presented
      varying amounts of stress around worrying about whether to disclose their
      diagnosis and whether they might transmit the disease to their family. In
      addition, in the cross-sectional data, 40% of the participants reported
      clinically significant sleep disturbances (GSDS > 3) with an average of 3 nights
      of disturbed sleep in the past week (M=2.87, SD=1.21) and moderate fatigue
      severity (M=5.24, SD=2.27). In mediation analyses, the data suggests that the
      relationship between perceived stress and fatigue was largely (53%) mediated
      through sleep disturbance. CONCLUSIONS: Chinese PLWHA described how stress had
      caused them to become sleepless and fatigued. The quantitative data also
      demonstrated significant levels of sleep disturbance and fatigue, where were due
      to perceived stress with HIV disease. A systematic self-management intervention
      to decrease perceived stress should be designed and implemented in mental health
      resource-limited settings such as China in order to reduce sleep disturbance and
      fatigue.

PMID- 24288656
TI  - Negative Affective Features in 516 Cases of First Psychotic Disorder Episodes:
      Relationship to Suicidal Risk.
AB  - OBJECTIVES: Plausible candidates of psychopathological phenomena that may
      associate with or anticipate suicidal risk, include negative affects, including
      admixtures of dysphoria, depression and anxiety described mainly in nonpsychotic
      disorders. We ascertained the distribution of such affective features in various
      first-episode psychotic disorders and correlated these and other clinical and
      antecedent features with intake suicidal status. METHODS: We evaluated 516 adult
      subjects in first-lifetime episodes of various DSM-IV-TR psychotic disorders.
      Blinded, protocol-guided, assessments of clinical features ascertained in SCID
      examinations, self- and family reports and clinical records supported analyses of
      associations of suicide attempts at first-psychotic episodes with antecedent and
      intake clinical characteristics, including negative affects and diagnoses, using
      standard bivariate and multivariate methods. RESULTS: Negative affective features
      in various combinations were prevalent (90%) and at >75% in both affective and
      nonaffective psychotic disorders; anxious depression was most common (22%). We
      identified antecedent and intake clinical factors preliminarily associated with
      suicide attempts. Factors remaining independently associated in multivariate
      logistic modelling (ranked by OR) were: (a) prior suicide attempt, (b) prior
      aggressive assault, (c) bipolar-mixed state or psychotic major depression
      diagnosis, (d) prior dysphoria, (e) intake dysphoric-anxiousdepression, (f) prior
      impulsivity, (g) previous affective instability, (h) previous nonpsychotic
      depression, (i) previous decline in vital drive, and (j) prior sleep
      disturbances. CONCLUSIONS: Various types and combinations of negative affective
      features (especially anxious depression with and without dysphoria) were
      prevalent across nonaffective as well as affective first psychotic episodes and
      strongly associated with suicide attempts. These findings extend previous
      observations in nonpsychotic disorders.

PMID- 24288657
TI  - Identification of putative ortholog gene blocks involved in gestant and lactating
      mammary gland development: a rodent cross-species microarray transcriptomics
      approach.
AB  - The mammary gland (MG) undergoes functional and metabolic changes during the
      transition from pregnancy to lactation, possibly by regulation of conserved
      genes. The objective was to elucidate orthologous genes, chromosome clusters and
      putative conserved transcriptional modules during MG development. We analyzed
      expression of 22,000 transcripts using murine microarrays and RNA samples of MG
      from virgin, pregnant, and lactating rats by cross-species hybridization. We
      identified 521 transcripts differentially expressed; upregulated in early (78%)
      and midpregnancy (89%) and early lactation (64%), but downregulated in mid
      lactation (61%). Putative orthologous genes were identified. We mapped the
      altered genes to orthologous chromosomal locations in human and mouse. Eighteen
      sets of conserved genes associated with key cellular functions were revealed and
      conserved transcription factor binding site search entailed possible coregulation
      among all eight block sets of genes. This study demonstrates that the use of
      heterologous array hybridization for screening of orthologous gene expression
      from rat revealed sets of conserved genes arranged in chromosomal order
      implicated in signaling pathways and functional ontology. Results demonstrate the
      utilization power of comparative genomics and prove the feasibility of using
      rodent microarrays to identification of putative coexpressed orthologous genes
      involved in the control of human mammary gland development. 

PMID- 24288658
TI  - Double-blind acupuncture needle: a potential tool to investigate the nature of
      pain and pleasure.
AB  - BACKGROUND: Most of our knowledge about similarities in the neural processing of
      painful and pleasant sensations in the brain derives from studying each
      phenomenon separately. Patients often feel pain induced by acupuncture, which is
      noxious stimulation having the symbolic message of the cure, as pleasant.
      OBJECTIVES: We investigated whether the double-blind acupuncture needles are
      potential tool to investigate coinciding pain and pleasant events. METHODS:
      Participants were 109 healthy acupuncture students. An acupuncturist applied the
      double-blind placebo and the matching penetrating needle at bilateral forearm of
      each subject, one needle on each side of the arm. We asked the subjects to rate
      the pain associated with needle application and its unpleasantness or
      pleasantness on a visual analogue scale. RESULTS: Of 65 penetrating needle
      applications that elicited pain, 29 (45%) subjects did not describe the pain as
      being unpleasant, and interestingly, 18 (28%) subjects described the needle
      insertion as pleasant. There was no significant difference in reported pain
      intensity between penetrating needles elicited pain that elicited a pleasant
      sensation and those that elicited an unpleasant sensation (P = 0.34).
      CONCLUSIONS: The double-blind acupuncture needles can be a potential tool for
      investigating the concomitant hedonic (pleasure) experience of pain.

PMID- 24288659
TI  - The forensiX evidence collection tube and its impact on DNA preservation and
      recovery.
AB  - Biological samples are vulnerable to degradation from the time they are collected
      until they are analysed at the laboratory. Biological contaminants, such as
      bacteria, fungi, and enzymes, as well as environmental factors, such as sunlight,
      heat, and humidity, can increase the rate of DNA degradation. Currently, DNA
      samples are normally dried or frozen to limit their degradation prior to their
      arrival at the laboratory. In this study, the effect of the sample drying rate on
      DNA preservation was investigated, as well as a comparison between drying and
      freezing methods. The drying performances of two commercially available DNA
      collection tools (swab and drying tube) with different drying rates were
      evaluated. The swabs were used to collect human saliva, placed into the drying
      tubes, and stored in a controlled environment at 25 degrees C and 60% relative
      humidity, or frozen at -20 degrees C, for 2 weeks. Swabs that were stored in fast
      sample drying tubes yielded 95% recoverable DNA, whereas swabs stored in tubes
      with slower sample drying rates yielded only 12% recoverable DNA; saliva stored
      in a microtube at -20 degrees C was used as a control. Thus, DNA sampling tools
      that offer rapid drying can significantly improve the preservation of DNA
      collected on a swab, increasing the quantity of DNA available for subsequent
      analysis. 

PMID- 24288660
TI  - A pipeline with multiplex reverse transcription polymerase chain reaction and
      microarray for screening of chromosomal translocations in leukemia.
AB  - Chromosome rearrangements and fusion genes present major portion of
      leukemogenesis and contribute to leukemic subtypes. It is practical and helpful
      to detect the fusion genes in clinic diagnosis of leukemia. Present application
      of reverse transcription polymerase chain reaction (RT-PCR) method to detect the
      fusion gene transcripts is effective, but time- and labor-consuming. To set up a
      simple and rapid system, we established a method that combined multiplex RT-PCR
      and microarray. We selected 15 clinically most frequently observed chromosomal
      rearrangements generating more than 50 fusion gene variants. Chimeric reverse
      primers and chimeric PCR primers containing both gene-specific and universal
      sequences were applied in the procedure of multiplex RT-PCR, and then the PCR
      products hybridized with a designed microarray. With this approach, among 200
      clinic samples, 63 samples were detected to have gene rearrangements. All the
      detected fusion genes positive and negative were validated with RT-PCR and Sanger
      sequencing. Our data suggested that the RT-PCR-microarray pipeline could screen
      15 partner gene pairs simultaneously at the same accuracy of the fusion gene
      detection with regular RT-PCR. The pipeline showed effectiveness in multiple
      fusion genes screening in clinic samples. 

PMID- 24288661
TI  - Alpha-lipoic acid attenuates renal injury in rats with obstructive nephropathy.
AB  - This study was established to determine the possible protective effects of alpha
      lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive
      nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral
      ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was
      injected intraperitoneally 2 days before UUO induction and continued afterward
      for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming
      growth factor-1 (TGF-beta1), and histological changes were evaluated at the end
      of the experiment. Obstruction of the ureter resulted in renal dysfunction as
      indicated by significant increases in blood urea nitrogen and serum creatinine.
      Nonobstructed contralateral kidneys in all groups examined did not show any
      morphological or biochemical alterations. In untreated UUO group, the obstructed
      kidney developed marked hydronephrosis, leukocyte infiltration, and severe
      interstitial fibrosis. These functional and structural changes were associated
      with significant increases in tissue levels of malondialdehyde, nitric oxide, and
      TGF- beta 1 but decreases in reduced glutathione and total antioxidant capacity.
      Pretreatment with ALA significantly minimized all the changes elicited by
      ureteral obstruction. These findings demonstrate that ALA supplementation
      attenuates renal injury in rats with obstructive nephropathy and further suggest
      that oxidative stress inhibition is likely to be involved in the beneficial
      effects of this compound.

PMID- 24288662
TI  - Phytochemicals content, antioxidant activity and acetylcholinesterase inhibition
      properties of indigenous Garcinia parvifolia fruit.
AB  - Garcinia parvifolia belongs to the same family as mangosteen (Garcinia
      mangostana), which is known locally in Sabah as "asam kandis" or cherry
      mangosteen. The present study was conducted to determine the phytochemicals
      content (total phenolic, flavonoid, anthocyanin, and carotenoid content) and
      antioxidant and acetylcholinesterase inhibition activity of the flesh and peel of
      G. parvifolia. All samples were freeze-dried and extracted using 80% methanol and
      distilled water. For the 80% methanol extract, the flesh of G. parvifolia
      displayed higher phenolic and flavonoid contents than the peel, with values of
      7.2 +/- 0.3 mg gallic acid equivalent (GAE)/g and 5.9 +/- 0.1 mg rutin equivalent
      (RU)/g, respectively. Anthocyanins were detected in the peel part of G.
      parvifolia but absent in the flesh. The peel of G. parvifolia displayed higher
      total carotenoid content as compared to the flesh part with the values of 17.0 +/
      0.3 and 3.0 +/- 0.0 mg beta-carotene equivalents (BC)/100 g, respectively. The
      free-radical scavenging, ferric reducing, and acetylcholinesterase inhibition
      effect of the flesh were higher as compared to the peel in both extracts. These
      findings suggested that the edible part of G. parvifolia fruit has a potential as
      a natural source of antioxidant and anti-Alzheimer's agents.

PMID- 24288663
TI  - Rapid induction of aldosterone synthesis in cultured neonatal rat cardiomyocytes
      under high glucose conditions.
AB  - In addition to classical adrenal cortical biosynthetic pathway, there is
      increasing evidence that aldosterone is produced in extra-adrenal tissues.
      Although we previously reported aldosterone production in the heart, the concept
      of cardiac aldosterone synthesis remains controversial. This is partly due to
      lack of established experimental models representing aldosterone synthase
      (CYP11B2) expression in robustly reproducible fashion. We herein investigated
      suitable conditions in neonatal rat cardiomyocytes (NRCMs) culture system
      producing CYP11B2 with considerable efficacy. NRCMs were cultured with various
      glucose doses for 2-24 hours. CYP11B2 mRNA expression and aldosterone
      concentrations secreted from NRCMs were determined using real-time PCR and enzyme
      immunoassay, respectively. We found that suitable conditions for CYP11B2
      induction included four-hour incubation with high glucose conditions. Under these
      particular conditions, CYP11B2 expression, in accordance with aldosterone
      secretion, was significantly increased compared to those observed in the cells
      cultured under standard-glucose condition. Angiotensin II receptor blocker
      partially inhibited this CYP11B2 induction, suggesting that there is local renin
      angiotensin-aldosterone system activation under high glucose conditions. The
      suitable conditions for CYP11B2 induction in NRCMs culture system are now
      clarified: high-glucose conditions with relatively brief period of culture
      promote CYP11B2 expression in cardiomyocytes. The current system will help to
      accelerate further progress in research on cardiac tissue aldosterone synthesis. 

PMID- 24288664
TI  - A posteriori comparison of natural and surgical destabilization models of canine
      osteoarthritis.
AB  - For many years Canis familiaris, the domestic dog, has drawn particular interest
      as a model of osteoarthritis (OA). Here, we optimized the dog model of
      experimental OA induced by cranial cruciate ligament sectioning. The usefulness
      of noninvasive complementary outcome measures, such as gait analysis for the limb
      function and magnetic resonance imaging for structural changes, was demonstrated
      in this model. Relationships were established between the functional impairment
      and the severity of structural changes including the measurement of cartilage
      thinning. In the dog model of naturally occurring OA, excellent test-retest
      reliability was denoted for the measurement of the limb function. A criterion to
      identify clinically meaningful responders to therapy was determined for privately
      owned dogs undergoing clinical trials. In addition, the recording of
      accelerometer-based duration of locomotor activity showed strong and
      complementary agreement with the biomechanical limb function. The translation
      potential of these models to the human OA condition is underlined. A preclinical
      testing protocol which combines the dog model of experimental OA induced by
      cranial cruciate ligament transection and the Dog model of naturally occurring OA
      offers the opportunity to further investigate the structural and functional
      benefits of disease-modifying strategies. Ultimately, a better prediction of
      outcomes for human clinical trials would be brought. 

PMID- 24288665
TI  - Enabling large-scale biomedical analysis in the cloud.
AB  - Recent progress in high-throughput instrumentations has led to an astonishing
      growth in both volume and complexity of biomedical data collected from various
      sources. The planet-size data brings serious challenges to the storage and
      computing technologies. Cloud computing is an alternative to crack the nut
      because it gives concurrent consideration to enable storage and high-performance
      computing on large-scale data. This work briefly introduces the data intensive
      computing system and summarizes existing cloud-based resources in bioinformatics.
      These developments and applications would facilitate biomedical research to make
      the vast amount of diversification data meaningful and usable. 

PMID- 24288666
TI  - Levels of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and
      organochlorine pesticides in various tissues of white-backed vulture in India.
AB  - This study provides information on the current status of contamination by
      polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and
      organochlorine pesticides (OCPs) in the tissues of endangered White-backed
      Vulture Gyps bengalensis in India. Chemical analyses revealed detectable amounts
      of PAHs, PCBs, and OCPs. Concentration ranges of ? PAHs, ? PCBs, and ? OCPs in
      tissues were 60-2037 ng/g, 30-5790 ng/g, and 3.2-5836 ng/g wet weight,
      respectively. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE)
      concentrations ranged from below detectable level to 599 ng/g wet weight,
      representing more than 90% of the total dichlorodiphenyltrichloroethane (DDT).
      Among the various OCPs analyzed, p,p'-DDE was detected most frequently. All the
      contaminants recorded show higher accumulation in liver than other tissues.
      Levels of contaminants measured in the tissues of vulture are comparable with the
      levels documented in a number of avian species and are lower than those reported
      to have caused deleterious effects. Although no threat is expected from the
      current level of contamination, the presence of varying levels of contaminants
      and their additive or synergistic toxicity is a cause of concern to vultures.
      Values reported in this study can serve as guideline for future research. 

PMID- 24288667
TI  - PSF knockdown enhances apoptosis via downregulation of LC3B in human colon cancer
      cells.
AB  - Our previous study demonstrated that PTB-associated splicing factor (PSF) is an
      important regulator of cell death and plays critical roles in the survival and
      growth of colon cancer cells. However, the molecular mechanism that activates
      these downstream signaling events remains unknown. To address this issue, we
      investigated the effects of PSF knockdown in two different colon cancer cell
      lines, DLD-1 and HT-29. We found that knockdown of PSF markedly decreased the
      autophagic molecule LC3B in DLD-1 cells but not in HT-29 cells. Furthermore, DLD
      1 cells were more susceptible to PSF knockdown-induced cell growth inhibition and
      apoptosis than HT-29 cells. This susceptibility is probably a result of LC3B
      inhibition, given the known relationship between autophagy and apoptosis. C3B is
      associated with a number of physiological processes, including cell growth and
      apoptotic cell death. Our results suggest that autophagy is inhibited by PSF
      knockdown and that apoptosis and cell growth inhibition may act together to
      mediate the PSF-LC3B signaling pathway. Furthermore, we found that the peroxisome
      proliferator-activated receptor gamma (PPARgamma)-PSF complex induced LC3B
      downregulation in DLD-1 cells. The results of this study identify a new
      physiological role for the PSF-LC3B axis as a potential endogenous modulator of
      colon cancer treatment.

PMID- 24288668
TI  - Selecting summary statistics in approximate Bayesian computation for calibrating
      stochastic models.
AB  - Approximate Bayesian computation (ABC) is an approach for using measurement data
      to calibrate stochastic computer models, which are common in biology
      applications. ABC is becoming the "go-to" option when the data and/or parameter
      dimension is large because it relies on user-chosen summary statistics rather
      than the full data and is therefore computationally feasible. One technical
      challenge with ABC is that the quality of the approximation to the posterior
      distribution of model parameters depends on the user-chosen summary statistics.
      In this paper, the user requirement to choose effective summary statistics in
      order to accurately estimate the posterior distribution of model parameters is
      investigated and illustrated by example, using a model and corresponding real
      data of mitochondrial DNA population dynamics. We show that for some choices of
      summary statistics, the posterior distribution of model parameters is closely
      approximated and for other choices of summary statistics, the posterior
      distribution is not closely approximated. A strategy to choose effective summary
      statistics is suggested in cases where the stochastic computer model can be run
      at many trial parameter settings, as in the example. 

PMID- 24288669
TI  - Transplantation of autologous minced bladder mucosa for a one-step reconstruction
      of a tissue engineered bladder conduit.
AB  - Surgical intervention is sometimes needed to create a conduit from the abdominal
      wall to the bladder for self-catheterization. We developed a method for tissue
      engineering a conduit for bladder emptying without in vitro cell culturing as a
      one-step procedure. In a porcine animal model bladder, wall tissue was excised
      and the mucosa was minced to small particles. The particles were attached to a
      tube in a 1 : 3 expansion rate with fibrin glue and transplanted back by
      attaching the tube to the bladder and through the abdominal wall. Sham served as
      controls. After 4-5 weeks, conduits were assessed in respect to macroscopic and
      microscopic appearance in 6 pigs. Two pigs underwent radiology before
      termination. Gross examination revealed a patent conduit with an opening to the
      bladder. Histology and immunostaining showed a multilayered transitional
      uroepithelium in all cases. Up to 89% of the luminal surface area was
      neoepithelialized but with a loose attachment to the submucosa. No epithelium was
      found in control animals. CT imaging revealed a patent channel that could be used
      for filling and emptying the bladder. Animals that experienced surgical
      complications did not form conduits. Minced autologous bladder mucosa can be
      transplanted around a tubular mold to create a conduit to the urinary bladder
      without in vitro culturing. 

PMID- 24288670
TI  - Circulating microRNAs and kallikreins before and after radical prostatectomy: are
      they really prostate cancer markers?
AB  - The aim of our study was to monitor serum levels of two miRNAs (miR-21 and miR
      141) and three KLKs (hK3/PSA, hK11, and hK13) before and 1, 5, and 30 days after
      radical prostatectomy, in order to characterize their fluctuations after surgery.
      38 patients with prostate cancer were included. miR-21 and miR-141 were
      quantified through real-time PCR, while ELISA assays were used to quantify hK3
      (PSA), hK11, and hK13. Both miR-21 and miR-141 showed a significant increase at
      the 5th postoperative day, after which a gradual return to the preoperative
      levels was recorded. These findings suggest that miR-21 and miR-141 could be
      involved in postsurgical inflammatory processes and that radical prostatectomy
      does not seem to alter their circulating levels. Postoperative serum kallikreins
      showed a significant decrease, highlighting the potential usefulness of
      kallikreins apart from PSA as potential prostate cancer markers. 

PMID- 24288671
TI  - The predictive value of interim and final [18F] fluorodeoxyglucose positron
      emission tomography after rituximab-chemotherapy in the treatment of non
      Hodgkin's lymphoma: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to determine the prognostic
      value of interim and final FDG-PET in major histotypes of B-cell NHL patients
      treated with rituximab containing-chemotherapy. METHODS: We searched for articles
      published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated
      to deal with the impact on progression and survival. The log hazard ratios (HR)
      and their variances were estimated. RESULTS: A PubMed and Scopus review of
      published trials identified 13 studies of Progression-free survival (PFS) and
      overall survival (OS) which were set as the main outcome measures. The combined
      HRs of I-PET for PFS and OS in DLBCL were 4.4 (P = 0.11) and 3.99 (P = 0.46),
      respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P =
      0.39) and 6.75 (P = 0.92), respectively. Regarding to non-DLBCL with F-PET, the
      combined HRs of F-PET for PFS and OS were 4.05 (P = 0.79) and 5.1 (P = 0.51),
      respectively. No publication bias existed. CONCLUSION: In DLBCL, both I-PET and F
      PET can be performed for survival and progression analysis. But in other B-cell
      subtypes such as follicular lymphoma (FL) and mantle cell lymphoma (MCL), it
      would be necessary to perform F-PET for predictive purposes.

PMID- 24288672
TI  - NSOM/QD-based visualization of GM1 serving as platforms for TCR/CD3 mediated T
      cell activation.
AB  - Direct molecular imaging of nanoscale relationship between T-cell receptor
      complexes (TCR/CD3) and gangliosidosis GM1 before and after T-cell activation has
      not been reported. In this study, we made use of our expertise of near-field
      scanning optical microscopy(NSOM)/immune-labeling quantum dots- (QD-)based dual
      color imaging system to visualize nanoscale profiles for distribution and
      organization of TCR/CD3, GM1, as well as their nanospatial relationship and their
      correlation with PKC theta signaling cascade during T-cell activation.
      Interestingly, after anti-CD3/anti-CD28 Ab co-stimulation, both TCR/CD3 and GM1
      were clustered to form nanodomains; moreover, all of TCR/CD3 nanodomains were
      colocalized with GM1 nanodomains, indicating that the formation of GM1
      nanodomains was greatly correlated with TCR/CD3 mediated signaling. Specially,
      while T-cells were pretreated with PKC theta signaling inhibitor rottlerin to
      suppress IL-2 cytokine production, no visible TCR/CD3 nanodomains appeared while
      a lot of GM1 nanodomains were still observed. However, while T-cells are
      pretreated with PKCalpha beta signaling inhibitor GO6976 to suppress calcium
      dependent manner, all of TCR/CD3 nanodomains were still colocalized with GM1
      nanodomains. These findings possibly support the notion that the formation of GM1
      nanodomains indeed serves as platforms for the recruitment of TCR/CD3
      nanodomains, and TCR/CD3 nanodomains are required for PKCtheta signaling cascades
      and T-cell activation.

PMID- 24288673
TI  - Transcriptome profile analysis of sugarcane responses to Sporisorium scitaminea
      infection using Solexa sequencing technology.
AB  - To understand the molecular basis of sugarcane-smut interaction, it is important
      to identify sugarcane genes that respond to the pathogen attack. High-throughput
      tag-sequencing (tag-seq) analysis by Solexa technology was performed on sugarcane
      infected with Sporisorium scitaminea, which should have massively increased the
      amount of data available for transcriptome profile analysis. After mapping to
      sugarcane EST databases in NCBI, we obtained 2015 differentially expressed genes,
      of which 1125 were upregulated and 890 downregulated by infection. Gene ontology
      (GO) analysis revealed that the differentially expressed genes involve in many
      cellular processes. Pathway analysis revealed that metabolic pathways and
      ribosome function are significantly affected, where upregulation of expression
      dominates over downregulation. Differential expression of three candidate genes
      involved in MAP kinase signaling pathway, ScBAK1 (GenBank Accession number:
      KC857629), ScMapkk (GenBank Accession number: KC857627), and ScGloI (GenBank
      Accession number: KC857628), was confirmed by reverse transcription polymerase
      chain reaction (RT-PCR). Real-time quantitative PCR (qRT-PCR) analysis concluded
      that the expression of these genes were all up-regulated after the infection of
      S. scitaminea and may play a role in pathogen response in sugarcane. The present
      study provides insights into the molecular mechanism of sugarcane defense to S.
      scitaminea infection, leading to a more comprehensive understanding of sugarcane
      smut interaction. 

PMID- 24288674
TI  - Gsk-3beta inhibitors mimic the cardioprotection mediated by ischemic pre- and
      postconditioning in hypertensive rats.
AB  - The aim of this study was to examine the effects of GSK-3 beta inhibitors
      compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated
      hearts were submitted to the following protocols: IC: 45 min global ischemia (GI)
      and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to
      45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other
      hearts received lithium chloride (LiCl) or indirubin-3'-monoxime,5-iodo-(IMI) as
      GSK-3 beta inhibitors. All interventions reduced the infarct size observed in IC
      group. The expressions of P-GSK-3 beta and P-Akt decreased in IC and were
      restored after PRE, POS, and GSK-3 beta inhibitors treatments. An increase of
      cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content
      observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An
      increase of P-GSK-3 beta /VDAC physical association and a partial recovery of
      mitochondrial permeability were also detected after interventions. These data
      show that, in SHR hearts, GSK-3 beta inhibitors mimic the cardioprotection
      afforded by PRE and POS and suggest that a decrease in mitochondrial permeability
      mediated by P-GSK-3 beta /VDAC interaction is a crucial event. 

PMID- 24288675
TI  - Citrus flavanones affect hepatic fatty acid oxidation in rats by acting as
      prooxidant agents.
AB  - Citrus flavonoids have a wide range of biological activities and positive health
      effects on mammalian cells because of their antioxidant properties. However, they
      also act as prooxidants and thus may interfere with metabolic pathways. The
      purpose of this work was to evaluate the effects of three citrus flavanones,
      hesperidin, hesperetin, and naringenin, on several parameters linked to fatty
      acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When
      exogenous octanoate was used as substrate, hesperetin and naringenin reduced the
      mitochondrial NADH/NAD+ ratio and stimulated the citric acid cycle without
      significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation
      from endogenous sources was evaluated, hesperetin and naringenin strongly reduced
      the mitochondrial NADH/NAD+ ratio. They also inhibited both oxygen uptake and
      ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand,
      had little to no effect on these parameters. These results confirm the hypothesis
      that citrus flavanones are able to induce a more oxidised state in liver cells,
      altering parameters related to hepatic fatty acid oxidation. The prooxidant
      effect is most likely a consequence of the ability of these substances to oxidise
      NADH upon production of phenoxyl radicals in the presence of peroxidases and
      hydrogen peroxide.

PMID- 24288676
TI  - Mass production of early-stage bone-marrow-derived mesenchymal stem cells of rat
      using gelatin-coated matrix.
AB  - Although preparation of early-stage bone-marrow-derived mesenchymal stem cells
      (BM-MSCs) is critical for successful cell transplantation therapy, no culture
      system offers a sufficient number of early-stage BM-MSCs for cell
      transplantation. Accordingly, we developed a culture system capable of producing
      a large number of early-stage BM-MSCs by using gelatin-coated matrix. The
      greatest retrieval and proliferation rates of the earliest-stage rat BM-MSCs were
      detected in bone-marrow-derived cells cultured on 1% (wt/v) gelatin-coated
      matrix, which showed significantly greater colony forming unit-fibroblast number,
      diameter, and total cell number. Moreover, continuous culture of the earliest
      stage BM-MSCs on 1% (wt/v) gelatin-coated matrix resulted in a maximum of 21.2 +/
      2.7 fold increase in the cumulative total number of early-stage BM-MSCs at
      passage 5. BM-MSCs generated in large quantities due to a reduced doubling time
      and an increased yield of cell population in S/G2/M phase showed typical
      fibroblast-like morphology and no significant differences in BM-MSC-related
      surface marker expression and differentiation potential, except for an increased
      ratio of differentiation into a neurogenic lineage. The use of gelatin-coated
      matrix in the retrieval and culture of BM-MSCs contributes greatly to the
      effective isolation and mass production of early-stage BM-MSCs. 

PMID- 24288677
TI  - Salamander-derived, human-optimized nAG protein suppresses collagen synthesis and
      increases collagen degradation in primary human fibroblasts.
AB  - Unlike humans, salamanders regrow their amputated limbs. Regeneration depends on
      the presence of regenerating axons which upregulate the expression of newt
      anterior gradient (nAG) protein. We had the hypothesis that nAG might have an
      inhibitory effect on collagen production since excessive collagen production
      results in scarring, which is a major enemy to regeneration. nAG gene was
      designed, synthesized, and cloned. The cloned vector was then transfected into
      primary human fibroblasts. The results showed that the expression of nAG protein
      in primary human fibroblast cells suppresses the expression of collagen I and
      III, with or without TGF- beta 1 stimulation. This suppression is due to a dual
      effect of nAG both by decreasing collagen synthesis and by increasing collagen
      degradation. Furthermore, nAG had an inhibitory effect on proliferation of
      transfected fibroblasts. It was concluded that nAG suppresses collagen through
      multiple effects. 

PMID- 24288678
TI  - Crocus sativus L. (saffron) stigma aqueous extract induces apoptosis in alveolar
      human lung cancer cells through caspase-dependent pathways activation.
AB  - Worldwide, lung cancer is the most common form of cancer. Saffron has been used
      in folk medicine for centuries. We investigated the potential of saffron to
      induce cytotoxic and apoptotic effects in lung cancer cells (A549). We also
      examined the caspase-dependent pathways activation of saffron-induced apoptosis
      against the A549 cells. A549 cells were incubated with different concentrations
      of saffron extract; then cell morphological changes, cell viability, and
      apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V
      and propidium iodide, and flow cytometric analysis, respectively. Activated
      caspases were detected by treatment of saffron in lung cancer cells using
      fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549
      cells were decreased after treatment with saffron in a dose- and time-dependent
      manner. The percentage of apoptotic cells increased with saffron concentrations.
      Saffron induced morphological changes, decreased percentage of viable cells, and
      induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate
      caspase pathways. The levels of caspases involved in saffron-induced apoptosis in
      the A549 cells indicating caspase-dependent pathway were induced by saffron. The
      anticancer activity of the aqueous extract of saffron could be attributed partly
      to its inhibition of the cell proliferation and induction of apoptosis in cancer
      cells through caspase-dependent pathways activation. 

PMID- 24288680
TI  - A light-field-based method to adjust on-axis rounded leaf end MLC position to
      predict off-axis MLC penumbra region dosimetric performance in a radiation
      therapy planning system.
AB  - PURPOSE: An analytical and experimental study of split shape dose calculation
      correction by adjusting the position of the on-axis round leaf end position is
      presented. We use on-axis corrected results to predict off-axis penumbra region
      dosimetric performance in an intensity-modulated radiation therapy treatment
      planning system. MATERIALS AND METHODS: The precise light-field edge position
      (X(tang.p)) was derived from the on-axis 50% dose position created by using the
      nominal light field for geometric and mathematical manipulation. Leaf position
      (X(mlc.p)) could be derived from X(tang.p) by defining in the treatment planning
      system for monitor unit calculation. On-axis offset (correction) could be
      obtained from the position corresponding to 50% of the central axis dose minus
      the X(mlc.p) position. The off-axis 50% dose position can then be derived from
      the on-axis 50% dose position. RESULTS: The monitor unit calculation of the split
      shape using the on-axis rounded leaf end MLC penumbra region could provide an
      under-or overdose of 7.5% per millimeter without an offset correction. When using
      the on-axis rounded leaf end offset correction to predict the off-axis dose, the
      difference between the off- and on-axis 50% dose position is within +/-1.5 mm.
      CONCLUSIONS: It is possible to achieve a dose calculation within 0.5% error for
      an adjusted MLC leaf edge location in the treatment planning system with careful
      measurement and an accurate on-axis offset correction. Dose calculations located
      at an off-axis spilt shape region should be used carefully due to noncorrectable
      errors which were found to be up to 10%.

PMID- 24288679
TI  - Human induced pluripotent stem cells from basic research to potential clinical
      applications in cancer.
AB  - The human induced pluripotent stem cells (hiPSCs) are derived from a direct
      reprogramming of human somatic cells to a pluripotent stage through ectopic
      expression of specific transcription factors. These cells have two important
      properties, which are the self-renewal capacity and the ability to differentiate
      into any cell type of the human body. So, the discovery of hiPSCs opens new
      opportunities in biomedical sciences, since these cells may be useful for
      understanding the mechanisms of diseases in the production of new diseases
      models, in drug development/drug toxicity tests, gene therapies, and cell
      replacement therapies. However, the hiPSCs technology has limitations including
      the potential for the development of genetic and epigenetic abnormalities leading
      to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress
      in the application of new strategies with the aim to enable an efficient
      production of high-quality of hiPSCs for safety and efficacy, necessary to the
      future application for clinical practice. In this review, we show the recent
      advances in hiPSCs' basic research and some potential clinical applications
      focusing on cancer. We also present the importance of the use of statistical
      methods to evaluate the possible validation for the hiPSCs for future therapeutic
      use toward personalized cell therapies. 

PMID- 24288681
TI  - Preparation and characterization of a gastric floating dosage form of
      capecitabine.
AB  - Gastrointestinal disturbances, such as nausea and vomiting, are considered
      amongst the main adverse effects associated with oral anticancer drugs due to
      their fast release in the gastrointestinal tract (GIT). Sustained release
      formulations with proper release profiles can overcome some side effects of
      conventional formulations. The current study was designed to prepare sustained
      release tablets of Capecitabine, which is approved by the Food and Drug
      Administration (FDA) for the treatment of advanced breast cancer, using
      hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium
      bicarbonate. Tablets were prepared using the wet granulation method and
      characterized such that floating lag time, total floating time, hardness,
      friability, drug content, weight uniformity, and in vitro drug release were
      investigated. The sustained release tablets showed good hardness and passed the
      friability test. The tablets' floating lag time was determined to be 30-200
      seconds, and it floated more than 24 hours and released the drug for 24 hours.
      Then, the stability test was done and compared with the initial samples. In
      conclusion, by adjusting the right ratios of the excipients including release
      retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and
      sodium bicarbonate, sustained release Capecitabine floating tablet was
      formulated. 

PMID- 24288682
TI  - 5-lipoxygenase deficiency reduces acetaminophen-induced hepatotoxicity and
      lethality.
AB  - 5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is
      involved in inflammation. At present, the participation of 5-LO in acetaminophen
      (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO
      deficient (5-LO-/-) mice and background wild type mice were challenged with APAP
      (0.3-6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage
      recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP
      induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next
      experiments. APAP induced LTB4 production in the liver, the primary target organ
      in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented
      reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP
      induced lethality, increase of plasma levels of aspartate aminotransferase and
      alanine aminotransferase, liver cytokine (IL-1beta, TNF-alpha , IFN- gamma, and
      IL-10), superoxide anion, and thiobarbituric acid reactive substances production,
      myeloperoxidase and N-acetyl-beta-D-glucosaminidase activity, Nrf2 and gp91(phox)
      mRNA expression, and decrease of reduced glutathione and antioxidant capacity
      measured by 2,2'-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were
      prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency
      resulted in reduced mortality due to reduced liver inflammatory and oxidative
      damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality
      and liver inflammatory/oxidative damage.

PMID- 24288683
TI  - Abacus training modulates the neural correlates of exact and approximate
      calculations in Chinese children: an fMRI study.
AB  - Exact (EX) and approximate (AP) calculations rely on distinct neural circuits.
      However, the training effect on the neural correlates of EX and AP calculations
      is largely unknown, especially for the AP calculation. Abacus-based mental
      calculation (AMC) is a particular arithmetic skill that can be acquired by long
      term abacus training. The present study investigated whether and how the abacus
      training modulates the neural correlates of EX and AP calculations by functional
      magnetic resonance imaging (fMRI). Neural activations were measured in 20 abacus
      trained and 19 nontrained Chinese children during AP and EX calculation tasks.
      Our results demonstrated that: (1) in nontrained children, similar neural regions
      were activated in both tasks, while the size of activated regions was larger in
      AP than those in the EX; (2) in abacus-trained children, no significant
      difference was found between these two tasks; (3) more visuospatial areas were
      activated in abacus-trained children under the EX task compared to the
      nontrained. These results suggested that more visuospatial strategies were used
      by the nontrained children in the AP task compared to the EX; abacus-trained
      children adopted a similar strategy in both tasks; after long-term abacus
      training, children were more inclined to apply a visuospatial strategy during
      processing EX calculations. 

PMID- 24288684
TI  - Classifying human voices by using hybrid SFX time-series preprocessing and
      ensemble feature selection.
AB  - Voice biometrics is one kind of physiological characteristics whose voice is
      different for each individual person. Due to this uniqueness, voice
      classification has found useful applications in classifying speakers' gender,
      mother tongue or ethnicity (accent), emotion states, identity verification,
      verbal command control, and so forth. In this paper, we adopt a new preprocessing
      method named Statistical Feature Extraction (SFX) for extracting important
      features in training a classification model, based on piecewise transformation
      treating an audio waveform as a time-series. Using SFX we can faithfully remodel
      statistical characteristics of the time-series; together with spectral analysis,
      a substantial amount of features are extracted in combination. An ensemble is
      utilized in selecting only the influential features to be used in classification
      model induction. We focus on the comparison of effects of various popular data
      mining algorithms on multiple datasets. Our experiment consists of classification
      tests over four typical categories of human voice data, namely, Female and Male,
      Emotional Speech, Speaker Identification, and Language Recognition. The
      experiments yield encouraging results supporting the fact that heuristically
      choosing significant features from both time and frequency domains indeed
      produces better performance in voice classification than traditional signal
      processing techniques alone, like wavelets and LPC-to-CC. 

PMID- 24288685
TI  - Low pH environmental stress inhibits LPS and LTA-stimulated proinflammatory
      cytokine production in rat alveolar macrophages.
AB  - Gastric aspiration increases the risks for developing secondary bacterial
      pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs) is
      an important mechanism in initiating innate immune host response. Effects of low
      pH stress, a critical component of aspiration pathogenesis, on the PRR pathways
      were examined, specifically toll-like receptor-2 (TLR2) and TLR4, using isolated
      rat alveolar macrophages (aMOs). We assessed the ability of aMOs after brief
      exposure to acidified saline to elaborate proinflammatory cytokines in response
      to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation, known
      ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA
      mediated cytokine release (CINC-1, MIP-2, TNF-alpha, MCP-1, and IFN-beta). LPS
      and LTA increased intracellular Ca2+ concentrations while Ca2+ chelation by BAPTA
      decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of
      low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated
      responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae
      clearance following acid aspiration. In conclusion, low pH stress inhibits
      antibacterial cytokine response of aMOs due to impaired TLR2 (MyD88 pathway) and
      TLR4 signaling (MyD88 and TRIF pathways). The role of Ca2+ in low pH stress
      induced signaling is complex but appears to be distinct between LPS- and LTA
      mediated responses.

PMID- 24288686
TI  - An investigation of vocal tract characteristics for acoustic discrimination of
      pathological voices.
AB  - This paper investigates the effectiveness of measures related to vocal tract
      characteristics in classifying normal and pathological speech. Unlike
      conventional approaches that mainly focus on features related to the vocal
      source, vocal tract characteristics are examined to determine if interaction
      effects between vocal folds and the vocal tract can be used to detect
      pathological speech. Especially, this paper examines features related to formant
      frequencies to see if vocal tract characteristics are affected by the nature of
      the vocal fold-related pathology. To test this hypothesis, stationary fragments
      of vowel /aa/ produced by 223 normal subjects, 472 vocal fold polyp subjects, and
      195 unilateral vocal cord paralysis subjects are analyzed. Based on the acoustic
      articulatory relationships, phonation for pathological subjects is found to be
      associated with measures correlated with a raised tongue body or an advanced
      tongue root. Vocal tract-related features are also found to be statistically
      significant from the Kruskal-Wallis test in distinguishing normal and
      pathological speech. Classification results demonstrate that combining the
      formant measurements with vocal fold-related features results in improved
      performance in differentiating vocal pathologies including vocal polyps and
      unilateral vocal cord paralysis, which suggests that measures related to vocal
      tract characteristics may provide additional information in diagnosing vocal
      disorders. 

PMID- 24288687
TI  - Rikkunshito, a Japanese kampo medicine, ameliorates decreased feeding behavior
      via ghrelin and serotonin 2B receptor signaling in a novelty stress murine model.
AB  - We investigated the effects of rikkunshito (RKT), a ghrelin signal enhancer, on
      the decrease in food intake after exposure to novelty stress in mice. RKT
      administration (500 mg/kg, per os) improved the decrease in 6 h cumulative food
      intake. In control mice, the plasma acylated ghrelin levels significantly
      increased by 24 h fasting. In contrast, the acylated ghrelin levels did not
      increase by fasting in mice exposed to the novelty stress. RKT administration to
      the novelty stress mice showed a significant increase in the acylated ghrelin
      levels compared with that in the distilled-water-treated control mice. Food
      intake after administering serotonin 2B (5-HT(2B)) receptor antagonists was
      evaluated to clarify the role of 5-HT(2B) receptor activation in the decrease in
      feeding behavior after novelty stress. SB215505 and SB204741, 5-HT(2B) receptor
      antagonists, significantly improved the decrease in food intake after exposure to
      novelty stress. A component of RKT, isoliquiritigenin, prevented the decrease in
      6 h cumulative food intake. Isoliquiritigenin showed 5-HT(2B) receptor
      antagonistic activity in vitro. In conclusion, the results suggested that RKT
      improves the decrease in food intake after novelty stress probably via 5-HT(2B)
      receptor antagonism of isoliquiritigenin contained in RKT.

PMID- 24288688
TI  - Microfluidics for synthesis of peptide-based PET tracers.
AB  - Positron emission tomography (PET) is a powerful noninvasive tool for acquisition
      of the physiological parameters in human and animals with the help of PET
      tracers. Among all the PET tracers, radiolabeled peptides have been widely
      explored for cancer-related receptor imaging due to their high affinity and
      specificity to receptors. But radiochemistry procedures for production of peptide
      based PET tracers are usually complex, which makes large-scale clinical studies
      relatively challenging. New radiolabeling technologies which could simplify
      synthesis and purification procedures, are extremely needed. Over the last
      decade, microfluidics and lab-on-a-chip (LOC) technology have boomed as powerful
      tools in the field of organic chemistry, which potentially provide significant
      help to the PET chemistry. In this minireview, microfluidic radiolabeling
      technology is described and its application for synthesis of peptide-based PET
      tracers is summarized and discussed. 

PMID- 24288689
TI  - Predictors of delayed antiretroviral therapy initiation, mortality, and loss to
      followup in HIV infected patients eligible for HIV treatment: data from an HIV
      cohort study in India.
AB  - Studies from Sub-Saharan Africa have shown that a substantial number of HIV
      patients eligible for antiretroviral therapy (ART) do not start treatment.
      However, data from other low- or middle-income countries are scarce. In this
      study, we describe the outcomes of 4105 HIV patients who became ART eligible from
      January 2007 to November 2011 in an HIV cohort study in India. After three years
      of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3%
      were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4
      count, longer duration of pre-ART care, belonging to a disadvantaged community,
      being widowed, and not living near a town were associated with delayed ART
      initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter
      duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and
      age >45 years were associated with mortality. Being homeless, being single, not
      living near a town, having a CD4 count <150 cells/MUL, and shorter duration of
      pre-ART care were associated with loss to followup. These results highlight the
      need to improve the timely initiation of ART in HIV programmes in India,
      especially in ART eligible patients with tuberculosis, low CD4 counts, living in
      rural areas, or having a low socioeconomic status.

PMID- 24288690
TI  - Animal models of diabetes and its associated complications.

PMID- 24288691
TI  - Analysis of cardiopulmonary stress during endoscopy: is unsedated transnasal
      esophagogastroduodenoscopy appropriate for elderly patients?
AB  - BACKGROUND: Transnasal esophagogastroduodenoscopy (EGD) without sedation has been
      reported to be safe and tolerable. It has recently been used widely in Japan for
      the detection of upper gastrointestinal disease. Alternatively, transoral
      examination using a thin endoscope has also been reported to be highly tolerable.
      OBJECTIVE: To examine the cardiocirculatory effects of transoral versus
      transnasal EGD in an attempt to determine the most suitable endoscopic methods
      for patients >=75 years of age. METHODS: Subjects who underwent monitoring of
      respiratory and circulatory dynamics without sedation during endoscopic screening
      examinations were enrolled at the New Ooe Hospital (Kyoto, Japan) between April
      2008 and March 2009. A total of 165 patients (age >=75 years) provided written
      informed consent and were investigated in the present study. Patients were
      randomly divided into three subgroups: UO group--thin endoscope; SO group-
      standard endoscope; and UT group--transnasal EGD. Percutaneous arterial blood
      oxygen saturation, heart rate and blood pressure were evaluated just before EGD
      and at five time points during EGD. After transnasal EGD, patients who had
      previously been examined using transoral EGD with a standard endoscope were asked
      about preferences for their next examination. RESULTS: There were no statistical
      differences in the characteristics among the groups. Percutaneous oxygen
      saturation in the UT group showed a transient drop compared with the SO and UO
      groups at the beginning of the endoscopic procedure. Heart rate showed no
      significant differences among the SO, UO and UT groups; Systolic blood pressure
      in the UO group was lower immediately after insertion compared with the SO and UT
      groups. The rate pressure product in the UO group was comparable with that in the
      UT group during endoscopy, and the SO group showed a continuously higher level
      than the UO and UT groups. More than one-half (54.4%) of patients were 'willing
      to choose transnasal EGD for next examination'. CONCLUSIONS: For elderly
      patients, unsedated transnasal EGD failed to show an advantage over unsedated
      standard endoscopy. Transoral thin EGD was estimated to be safe and tolerable.

PMID- 24288692
TI  - Outcomes of pediatric laparoscopic fundoplication: a critical review of the
      literature.
AB  - BACKGROUND/OBJECTIVE: Laparoscopic fundoplication for gastroesophageal reflux
      disease (GERD) is one of the most common procedures performed in children. A
      critical literature review was performed to evaluate the level and quality of
      evidence supporting the efficacy of this procedure. METHODS: Systematic reviews
      of the EMBASE, PubMed and CENTRAL databases were conducted to retrieve all
      articles published over a 15-year period (1996 to 2010) reporting medium- to long
      term outcomes (minimum six months follow-up) of laparoscopic fundoplication for
      the treatment of pediatric GERD. Articles were critically appraised using the
      Newcastle-Ottawa quality assessment scale and the Cochrane risk of bias
      assessment tool. Extracted outcomes included GERD recurrence, need for
      reoperation, postoperative morbidity and mortality. RESULTS: A total of 5302
      articles were retrieved. Thirty-six studies met inclusion and exclusion criteria,
      including five prospective (level 2b), four retrospective comparative (level 3b)
      and 27 case series (level 4). No studies compared laparoscopic fundoplication
      with medical treatment. Thirty-six per cent of studies did not describe the
      symptoms used to suspect GERD; 11% did not disclose the diagnostic modalities
      used; and 41% did not report the findings of diagnostic modalities. Only 17% of
      studies provided a definition of recurrence, and only 14% attempted to control
      for confounding variables. The follow-up intervals were inconsistently reported,
      ranging between two months and nine years. Significant heterogeneity among
      studies limited the ability to pool outcomes. Mean (+/- SD) recurrence rates
      varied between 0% and 48+/-19.6% of patients. Reoperation was required in 0.69+/
      0.95% to 17.7+/-8.4% of patients. Mortality ranged between 0% and 24+/-16.7%.
      CONCLUSION: The level and quality of the evidence supporting laparoscopic
      fundoplication are extremely poor. Higher-quality data are required before the
      procedure can be considered to be an effective intervention in the treatment of
      pediatric GERD.

PMID- 24288693
TI  - Third-generation cephalosporin-resistant spontaneous bacterial peritonitis: a
      single-centre experience and summary of existing studies.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is the most prevalent
      bacterial infection in patients with cirrhosis. Although studies from Europe have
      reported significant rates of resistance to third-generation cephalosporins,
      there are limited SBP-specific data from centres in North America. OBJECTIVE: To
      evaluate the prevalence of, predictors for and clinical impact of third
      generation cephalosporin-resistant SBP at a Canadian tertiary care centre, and to
      summarize the data in the context of the existing literature. METHODS: SBP
      patients treated with both antibiotics and albumin therapy at a Canadian tertiary
      care hospital between 2003 and 2011 were retrospectively identified. Multivariate
      logistic regression was used to determine independent predictors of third
      generation cephalosporin resistance and mortality. RESULTS: In 192 patients, 25%
      of infections were nosocomial. Forty per cent (77 of 192) of infections were
      culture positive; of these, 19% (15 of 77) were resistant to third-generation
      cephalosporins. The prevalence of cephalosporin resistance was 8% with community
      acquired infections, 17% with health care-associated infections and 41% with
      nosocomial acquisition. Nosocomial acquisition of infection was the only
      predictor of resistance to third-generation cephalosporins (OR 4.0 [95% CI 1.04
      to 15.2]). Thirty-day mortality censored for liver transplantation was 27% (50 of
      184). In the 77 culture-positive patients, resistance to third-generation
      cephalosporins (OR 5.3 [1.3 to 22]) and the Model for End-stage Live Disease
      score (OR 1.14 [1.04 to 1.24]) were independent predictors of 30-day mortality.
      CONCLUSIONS: Third-generation cephalosporin-resistant SBP is a common diagnosis
      and has an effect on clinical outcomes. In an attempt to reduce the mortality
      associated with resistance to empirical therapy, high-risk subgroups should
      receive broader empirical antibiotic coverage.

PMID- 24288694
TI  - Follow-up of participants in the Canadian Association of Gastroenterology
      Scholars' Program, 2006 to 2012.
AB  - The Canadian Association of Gastroenterology (CAG) Scholars' Program (previously
      known as the Bright Lights Course) is designed to encourage trainees to consider
      a subspecialty career in gastroenterology. A formal analysis of the Scholars'
      Program performed in 2007 revealed that 82% of participants invited to the
      program pursued or were planning to pursue a career in gastroenterology. The
      positive results are consistent with the CAG's strategic plan of developing "the
      next generation of gastroenterology clinical practitioners, researchers,
      educators, and leaders" and to "attract, train, and retain the best and the
      brightest to gastroenterology". The present study was a follow-up analysis of
      participants in the Scholars' Program between 2006 and 2012. Although 93.1% of
      participants had an interest in gastroenterology before attending the Scholars'
      Program, the majority (68.7%) reported a greater interest in gastroenterology
      after the program. Similar to the study from 2007, the present study again
      illustrates the importance and success of the Scholars' Program in generating
      interest and retaining candidates in gastroenterology.

PMID- 24288695
TI  - Comparing outcomes of donation after cardiac death versus donation after brain
      death in liver transplant recipients with hepatitis C: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Liver transplantation (LT) using organs donated after cardiac death
      (DCD) is increasing due, in large part, to a shortage of organs. The outcome of
      using DCD organs in recipients with hepatits C virus (HCV) infection remains
      unclear due to the limited experience and number of publications addressing this
      issue. OBJECTIVE: To evaluate the clinical outcomes of DCD versus donation after
      brain death (DBD) in HCV-positive patients undergoing LT. METHODS: Studies
      comparing DCD versus DBD LT in HCV-positive patients were identified based on
      systematic searches of seven electronic databases and multiple sources of gray
      literature. RESULTS: The search identified 58 citations, including three studies,
      with 324 patients meeting eligibility criteria. The use of DCD livers was
      associated with a significantly higher risk of primary nonfunction (RR 5.49 [95%
      CI 1.53 to 19.64]; P=0.009; I2=0%), while not associated with a significantly
      different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I2=51%), graft
      survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I2=34%), rate of recurrence of
      severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I2=84%),
      retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84];
      P=0.25; I2=44%), and biliary complications. CONCLUSIONS: While the literature and
      quality of studies assessing DCD versus DBD grafts are limited, there was
      significantly more primary nonfunction and a trend toward decreased graft
      survival, but no significant difference in biliary complications or recipient
      mortality rates between DCD and DBD LT in patients with HCV infection. There is
      insufficient literature on the topic to draw any definitive conclusions.

PMID- 24288696
TI  - Granulomatous lymphocytic interstitial lung disease in infancy.
AB  - The authors report a case involving a child with chronic respiratory symptoms,
      who did not respond to conventional treatment. Low serum immunoglobin levels and
      pathological findings on lung biopsy revealed an unusual diagnosis for his age
      group. A specific treatment led to clinical improvement. 

PMID- 24288697
TI  - The respiratory presentation of severe combined immunodeficiency in two Mennonite
      children at a tertiary centre highlighting the importance of recognizing this
      pediatric emergency.
AB  - Severe combined immunodeficiency (SCID) is considered to be a pediatric
      emergency, with respiratory distress being the most common presenting symptom.
      The authors present two cases of SCID in children <4 months of age with
      respiratory distress at a tertiary care centre due to a recently described
      homozygous CD3 delta mutation found only in the Mexican Mennonite population.
      Failure to respond to broad-spectrum antibiotics prompted investigation for
      possible SCID. Bronchial alveolar lavage fluid from both patients grew
      Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta
      gene is believed to be important in T cell differentiation and maturation. The
      present article reminds pediatricians and pediatric respirologists that the key
      to diagnosing SCID is to have a high index of suspicion if there is poor response
      to conventional therapies. 

PMID- 24288698
TI  - Sleep laboratory test referrals in Canada: sleep apnea rapid response survey.
AB  - BACKGROUND: An estimated 5.4 million Canadian adults have been diagnosed with
      sleep apnea or are at high risk of experiencing obstructive sleep apnea (OSA).
      There are no recent Canadian data regarding access to and predictors of referral
      for diagnostic testing in these populations. METHODS: The Sleep Apnea Rapid
      Response survey sampled 8647 Canadian adults and captured information about risk,
      testing, diagnosis and treatment of sleep apnea. Predictors of sleep laboratory
      test referrals were assessed using log-linked binomial regression modelling.
      Information regarding sleep testing facilities was updated at the provincial and
      regional levels. RESULTS: Approximately 76.8% (95% CI 70.1% to 83.6%) of adult
      Canadians with sleep apnea and 5.1% (95% CI 3.4% to 6.7%) of those at high risk
      for OSA reported being referred to a sleep laboratory. Significant predictors of
      sleep laboratory referral in the general population were male sex, middle age,
      overweight or obese, a chronic condition, having a regular medical doctor and
      reporting symptoms of sleep apnea. Region of residence was also a predictor of
      reported sleep laboratory referral, with individuals from Ontario being more
      likely to report being referred to a sleep laboratory versus individuals from
      other regions. CONCLUSION: Individuals reporting risk factors and symptoms
      associated with OSA were more likely to report a sleep laboratory testing
      referral compared with those without risk factors or symptoms. However, Canada's
      diagnostic sleep laboratory testing capacity varies across regions and is
      believed to be inadequate given the number of individuals at high risk for OSA
      who did not report testing referral.

PMID- 24288699
TI  - Use of a level 3 portable monitor for the diagnosis and management of sleep
      disordered breathing in an inpatient tertiary care setting.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) may impact the course of medical
      illness among hospitalized patients. Access to testing during hospitalization to
      assess this may be limited by wait times for laboratory polysomnography. Level 3
      portable monitoring (PM) may provide an alternative. OBJECTIVE: To assess the
      rate of technically adequate studies, diagnostic information obtained and impact
      on patient management of inpatient PM studies performed for SDB. METHODS: A
      retrospective review of 114 PM (Embletta, Natus Inc, Canada) records from the
      past two years was performed. Studies were ordered by pulmonologists, initiated
      by respiratory therapists and performed unattended on inpatient units. Admitting
      diagnoses, indication for sleep study, diagnostic information obtained from
      recordings and change in clinical management subsequent to PM were determined
      from medical charts. RESULTS: Of 114 studies reviewed, 99 (87%) met predetermined
      criteria for adequate signal quality and duration. Five studies could not be
      interpreted due to inadequate data, yielding an overall success rate of 83% (94
      of 114). Of 86 studies performed for diagnosis, clinical and PM data supported a
      new diagnosis of SDB in 55 patients, of which 23 (42%) were started on positive
      pressure therapy. Thirteen PM studies were performed during SDB treatment. All
      were technically adequate and six of 13 demonstrated new or persistent SDB.
      Results from PM testing informed clinical management during hospitalization in 70
      (61%) cases. CONCLUSION: Unattended level 3 PM studies are technically feasible
      in hospitalized patients and may provide information that influences clinical
      management.

PMID- 24288701
TI  - PSA screening: the USPSTF got it wrong.

PMID- 24288700
TI  - Identification and validation of nebulized aerosol devices for sputum induction.
AB  - BACKGROUND: Induced sputum cell counts are a noninvasive and reliable method for
      evaluating the presence, type and degree of airway inflammation in patients with
      asthma. Currently, standard nebulizer devices used for sputum induction in
      multiple patients are labelled as single-patient devices by the manufacturer,
      which conflicts with infection prevention and control requirements. As such,
      these devices cannot feasibly be used in a clinical sputum induction program.
      Therefore, there is a need to identify alternative nebulizer devices that are
      either disposable or labelled for multipatient use. OBJECTIVE: To apply validated
      rigorous, scientific testing methods to identify and validate commercially
      available nebulizer devices appropriate for use in a clinical sputum induction
      program. METHODS: Measurement of nebulized aerosol output and size for the
      selected nebulizer designs followed robust International Organization for
      Standardization methods. Sputum induction using two of these nebulizers was
      successfully performed on 10 healthy adult subjects. The cytotechnologist
      performing sputum cell counts was blinded to the type of nebulizer used. RESULTS:
      The studied nebulizers had variable aerosol outputs. The AeroNeb Solo (Aerogen,
      Ireland), Omron NE-U17 (Omron, Japan) and EASYneb II (Flaem Nuova, Italy) systems
      were found to have similar measurements of aerosol size. There was no significant
      difference in induced sputum cell results between the AeroNeb Solo and EASYneb II
      devices. DISCUSSION: There is a need for rigorous, scientific evaluation of
      nebulizer devices for clinical applications, including sputum induction, for
      measurement of cell counts. CONCLUSION: The present study was the most
      comprehensive analysis of different nebulizer devices for sputum induction to
      measure cell counts, and provides a framework for appropriate evaluation of
      nebulizer devices for induced sputum testing.

PMID- 24288702
TI  - PSA screening: the USPSTF got it right.

PMID- 24288703
TI  - An instructive tale about "hamburgers".

PMID- 24288704
TI  - Readers weigh in on venous ulcer treatment.

PMID- 24288705
TI  - Readers weigh in on venous ulcer treatment.

PMID- 24288706
TI  - Author response: Venous ulcer treatment.

PMID- 24288707
TI  - A practical guide to community-acquired MRSA.
AB  - As the number of CA-MRSA skin and soft tissue infections continues to grow, it's
      important to know which patients are at greatest risk and which evidence-based
      treatment protocols to turn to when needed. 

PMID- 24288708
TI  - Mammography at age 40? A risk-based strategy.
AB  - Breast cancer screening starting at age 40 continues to be controversial. Breast
      density--established with a baseline mammogram--is a key factor in the authors'
      algorithmic approach.

PMID- 24288709
TI  - Fecal incontinence: help for patients who suffer silently.
AB  - Once you've identified patients with this embarrassing condition, achieving
      optimal outcomes hinges on your familiarity with advances like sacral nerve
      stimulation. 

PMID- 24288710
TI  - PURLs: Is self-swabbing for STIs a good idea?

PMID- 24288711
TI  - An incidental finding.
AB  - Pruritic patches on the patient's trunk and extremities prompted his visit, but
      it was the "birthmark" on his back that was far more worrisome. 

PMID- 24288712
TI  - Clinical inquiry: How do antidepressants affect sexual function?

PMID- 24288713
TI  - Clinical inquiry: Do oral contraceptives carry a significant risk of stroke for
      women with migraines?

PMID- 24288714
TI  - PURLs: Should you screen for postpartum depression?

PMID- 24288715
TI  - Open field behavior and the state of the thymus and adrenal glands in rats after
      exposure to stress and elevation of blood level of autoantibodies to dopamine and
      glutamate.
AB  - Blood level of autoantibodies to dopamine and glutamate in rats increased in 4
      weeks after exposure to stress. Under these conditions, active animals
      demonstrated decreased motor and exploratory activity in the open field, while in
      passive animals, only the number of explored objects decreased. The increase in
      blood level of autoantibodies to dopamine and glutamate in rats exposed to stress
      was followed by an increase in the adrenal gland weight in active animals and
      thymus weight in passive animals. The increased blood level of autoantibodies to
      dopamine and glutamate in rats exposed to stress reflects the development of the
      long-term stress-induced response. 

PMID- 24288716
TI  - Effects of electric stimulation of the hunger center in the lateral hypothalamus
      on slow electric activity and spike activity of fundal and antral stomach muscles
      in rabbits under conditions of hunger and satiation.
AB  - In chronic experiments on rabbits, the effect of electric stimulation of the
      hunger center in the lateral hypothalamus on myoelectric activity of the fundal
      and antral parts of the stomach was studied under conditions of hunger and
      satiation in the absence of food. Stimulation of the lateral hypothalamus in
      rabbits subjected to 24-h food deprivation and in previously fed rabbits produced
      incessant seeking behavior, which was followed by reorganization of the structure
      of temporal organization of slow wave electric activity of muscles of the stomach
      body and antrum specific for hungry and satiated animals. Increased hunger
      motivation during electric stimulation of the lateral hypothalamus manifested in
      the structure of temporal organization of slow wave electric activity of the
      stomach body and antrum muscles in rabbits subjected to 24-h food deprivation in
      the replacement of bimodal distribution of slow wave periods to a trimodal type
      typical of 2-day deprivation, while transition from satiation to hunger caused by
      electric stimulation of the lateral hypothalamus was associated with a shift from
      monomodal distributions of slow wave periods to a bimodal type typical of 24-h
      deprivation. Reorganization of the structure of temporal organization of slow
      wave electric activity of the stomach body and antrum muscles during electric
      stimulation of the lateral hypothalamus was determined by descending inhibitory
      influences of food motivational excitation on activity of the myogenic pacemaker
      of the lesser curvature of the stomach. 

PMID- 24288717
TI  - Role of nitric oxide in responses of pial arterial vessels to low-intensity red
      laser irradiation.
AB  - The responses of rat pial vessels to red laser irradiation can be mediated by NO.
      NO mainly affects major arteries and did not contribute to reactivity of small
      pial arteries and precortical arterioles.

PMID- 24288718
TI  - Effects of preliminary hypokinetic stress on sensitivity of the bone marrow to
      the hypoplastic effect of exogenous glucocorticoid.
AB  - We studied the cell composition and free radical oxidation in the bone marrow of
      white outbred rats after hypokinetic stress (24 and 72 h) and the effects of
      exogenous glucocorticoid triamcinolone acetonide (2 mg/kg; injected 24 h after
      hypokinesia); the measurements were performed in 96 h after drug administration.
      The hypoplastic effect of the glucocorticoid after 24-h hypokinesia was observed
      against the background of reduced free radical oxidation. In animals subjected to
      3-day hypokinesia, the resistance of the bone marrow to the hypoplastic effect of
      this drug was accompanied by activation of free radical processes. 

PMID- 24288719
TI  - Comparative characteristics of the cytochemical status of peritoneal and alveolar
      macrophages in the progeny of female rats with experimental liver disease.
AB  - The effects of experimental maternal chronic liver disease (induced by injection
      of hepatotropic toxin D(+)-galactosamine hydrochloride) on cytochemical activity
      of peritoneal and alveolar macrophages of the progeny were studied at different
      stages of postnatal development. Maternal hepatobiliary disease caused a
      reduction of the functional activity of macrophageal cells in the progeny, which
      manifested by inhibition of the lysosomal and peroxidase activities and low level
      of acid phosphatase. 

PMID- 24288720
TI  - Effects of antibodies to glutamate on focal penicillin-induced epileptic
      activity.
AB  - The effects of intranasal pretreatment with antibodies against glutamate on focal
      penicillin-induced epileptic activity were studied by recording
      electrocorticogram in non-anesthetized freely moving male Wistar rats.
      Anticonvulsant effects of intranasal administration of anti-glutamate antibodies
      (300 MUg/kg) 1 h before application of penicillin (30,000 U/ml) on the
      sensorimotor cortex was demonstrated: the latency of ictal discharges increased
      and their frequency decreased.

PMID- 24288721
TI  - Characteristics of circadian rhythm of blood pressure during long-term
      hypertension development in SHR rats.
AB  - The specific features of circadian rhythm of BP were investigated in freely
      moving male SHR rats using telemetry monitoring technique. BP was recorded in the
      abdominal aorta according to 24-h/4-month schedule. The data were obtained from
      22, 26, 30, 34, and 38-week-old animals. Normotensive Wistar rats (22 weeks)
      served as the control. It was found that the mean 24-h, daytime, and nighttime
      systolic and diastolic BP in hypertensive rats significantly surpassed the
      control throughout the observation period and practically did not change during
      prolonged hypertension. Some prognostically negative changes in the circadian
      rhythm of the basic hemodynamics system parameters appeared with time. For
      instance, the maximum 24-h systolic BP significantly increased in comparison with
      the initial level. 

PMID- 24288722
TI  - Role of epithelial sodium channel in the realization of homeostatic effects of
      aldosterone on the volume of principal cells of cortical collecting ducts in rats
      after hypoosmotic stress.
AB  - The mechanism of aldosterone effects (10 nM) on the volume of the principal cells
      of cortical collecting ducts after hypoosmotic stress (280/140 mOsm/kg) was
      studied using fluorescence microscopy. The experiments with intracellular
      fluorescent dye calcein showed that aldosterone significantly decreases the
      amplitude and rate of increase in principal cell volume during hypoosmotic
      stress. Epithelial sodium channel blocker amiloride (10(-5)M) significantly
      attenuated the effects of aldosterone on the amplitude and rate of changes in
      cell volume. The obtained data attest to the contribution of epithelial sodium
      channel to the realization of rapid non-genomic effects of aldosterone on the
      amplitude and rate of changes in volume of the principal cells of cortical
      collecting ducts in rat kidney after hypoosmotic stress. 

PMID- 24288723
TI  - Histoenzymological characteristics of the heart conduction system: comparative
      study with left or right ventricle afterload.
AB  - Histoenzymological changes, indicating inhibition of the main metabolic
      processes, were found in the conduction cardiomyocytes of the left ventricle and
      ventricular septum in experimental stenosis of the aorta. The histoenzymological
      changes in the conduction system of both ventricles and ventricular septum were
      similar in experimental stenosis of the pulmonary artery and indicated primarily
      activation of glycolysis. The histoenzymological profile of conduction
      cardiomyocytes differed little in cases when the increase of the pressure load
      was complicated or not complicated by the development of heart failure,
      particularly in pulmonary artery stenosis. The histoenzymological changes in the
      conduction system in response to increased afterload differed significantly from
      those in the contractile myocardium and correlated with the level of cellular
      functional activity and sensitivity to the regulatory and alterative exposure.
      These data attest to minor role of metabolic shifts in conduction cell injuries
      with increasing afterload, primarily, of the right ventricle. 

PMID- 24288724
TI  - Production of active oxygen species by blood phagocytes of pregnant women and
      their newborns with intrauterine infection.
AB  - We studied the relationship between changes in the maternal and newborn
      granulocyte functions under conditions of infection risk and realization. Women
      with normal gestation and their healthy newborns, pregnant women with a high risk
      of infection and their newborns, healthy or with intrauterine infection, were
      examined. Changes in the active oxygen species-dependent phagocytosis system were
      found in the blood of risk group patients. An inverse relationship between the
      parameters venous and umbilical cord blood was detected indicating a relationship
      between changes in functional activities of maternal and newborn granulocytes.
      The percentage of CD11b(+)cells in venous and umbilical cord blood strictly
      correlated with the percent of cells that phagocytosed FITC-labeled E. coli.
      Deviations in the generation of active oxygen species in phagocytosis seemed to
      be related to the expression of surface receptors in the risk groups. 

PMID- 24288725
TI  - Analysis of biochemical changes in rat erythrocytes induced by long-term
      simvastatin treatment.
AB  - Analysis of metabolic changes in rat erythrocytes against the background of long
      term simvastatin treatment revealed an increase in glycolysis metabolite
      concentrations and glucose-6-phosphate dehydrogenase activity and oppositely
      directed shifts in antioxidant defense enzyme activities. It was demonstrated
      that hypoxia and imbalance in the antioxidant enzyme system contribute to the
      development of side effects of statins. 

PMID- 24288726
TI  - Comparison of specific activity of granulocytopoiesis stimulators after treatment
      with cytostatics with different mechanisms of action.
AB  - We compared hemostimulating effects of glyciram, pantohematogen, granulocytic
      CSF, and D-glucuronic acid preparation on the granulocytic lineage hemopoiesis
      suppressed by cyclophosphamide or 5-fluorouracil. The effects hemostimulators
      against the background of 5-fluorouracil treatment were less pronounced that
      during cyclophosphamide treatment. 

PMID- 24288727
TI  - Effects of drugs on exercise performance.
AB  - The effects of 15 preparations with general tonic, antioxidant, and antihypoxant
      activities on exercise performance of laboratory rats were studied in the forced
      swimming test. The best recovery and improvement of exercise performance was
      recorded after a single intragastric dose of schizandrin and acyzol. These drugs
      stimulated an increase in the parameters in control animals by 86 and 72%
      (exercise performance recovery) and by 33 and 51% (exercise performance
      improvement). 

PMID- 24288728
TI  - Effects of naltrexone on firing activity of rat cortex neurons and its
      interactions with ethanol.
AB  - Naltrexone dose-dependently decreased neuron firing rate in the rat frontal
      cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration.
      Microelectrophoretic applications of naltrexone reduced the excitatory neuronal
      response of neurons to low doses of ethanol (electroosmotic application) and
      potentiated depression of firing activity induced by ethanol in high doses. We
      concluded that opioid peptides take part in generation of spontaneous neuronal
      activity in the frontal cortex and neuronal excitation caused by ethanol in low
      doses. Naltrexone acts as a synergist of ethanol in its depressive effect on
      cortical neurons. 

PMID- 24288729
TI  - Study of hepatoprotective effects of xymedon.
AB  - Xymedon (1-(beta-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine), a
      regeneratory and wound-healing drug, exhibited hepatoprotective activity in
      laboratory animals with experimental toxic hepatitis. Oral drug reduced the
      severity of toxic involvement of the liver induced by CCl4 and reduced animal
      mortality. Xymedon promoted recovery of the blood biochemical parameters
      characterizing the liver status.

PMID- 24288730
TI  - Methodological aspects of optimizing the choice of plants for creation of new
      drugs.
AB  - An integrative systemic model of pharmacological reaction to a phytopreparation
      was created as a result of conceptual structurization of facts and formalization
      of causal relations. The use of the new methodological approach to the choice,
      primary screening, and profound studies of plants for prospective addition
      thereof to the list of officinal medicinal plants was studied. Use of modern
      information technologies makes it possible to minimize the labor and time
      consumption and to carry out automated search, studies of new plant objects, and
      creation on this base of drugs with scientifically valid therapeutic efficiency. 

PMID- 24288731
TI  - Effect of BMP-2 protein on the count and osteogenic properties of multipotent
      stromal cells and expression of cytokine genes in primary cultures of bone marrow
      and spleen cells from CBA mice immunized with bacterial antigens.
AB  - We studied the effect of BMP-2 added to the culture medium on osteogenic and
      proliferative properties of multipotent stromal cells (MSC) and on the expression
      of cytokine genes induced by immunization of experimental animals with bacterial
      antigens. It is shown that the presence of BMP-2 in the culture medium stimulates
      proliferation of bone marrow MSC and especially spleen MSC (which was seen from
      enlargement of MSC colonies); improves the efficiency of MSC cloning; increases
      osteogenic activity of mouse bone marrow MSC; induces osteogenic differentiation
      of splenic MSC (osteogenesis is normally not observed in the spleen); reduces the
      number of macrophages in cultures; inhibits synthesis of mRNA for proinflammatory
      cytokines (IL-1beta, IL-6, IL-8, TNF-alpha) that typically occurs in cultures of
      the bone marrow and spleen from animals immunized with S. typhimurium or group A
      streptococcus antigens. Bearing in mind that proinflammatory cytokines negatively
      affect osteogenic activity of the bone marrow, we can hypothesize that BMP-2 not
      only stimulates osteogenesis, but also provides optimal conditions for its
      realization by suppressing the expression of genes encoding these cytokines. 

PMID- 24288732
TI  - In vitro study of phenotypical characteristics of BCG granuloma macrophages over
      the course of granuloma development.
AB  - Structural and immunophenotypical characteristics of macrophages, associated with
      their polarization in the M1 and M2 directions of differentiation and activation,
      were studied in different morphological types of BCG granulomas by the expression
      of GM-CSF, IFN-gamma, and FGFb cytokines and CD36 and CD16/32 differentiation
      clusters. The proportion of IFN-gamma and FGFb macrophage subpopulations changed
      over the course of granuloma formation, which led to accumulation of FGFb
      macrophages in the granulomas. These data indicated that the formation of
      macrophage granulomas and their subsequent transformation into epithelioid-cell
      granulomas were associated with dynamic quantitative changes in the
      subpopulations of macrophages with the morphofunctional characteristics of M1 and
      M2 phenotypes, determining the antibacterial and destructive potential of
      granulomas. These data are useful for understanding the contribution of
      functional polarization of macrophages to the pathogenesis of tuberculous
      infection and, presumably, its complications. 

PMID- 24288733
TI  - Effects of experimental desynchronosis on the organs of immune system in WAG and
      ISIAH rats.
AB  - We studied the influence of abnormal illumination regimen on cell composition of
      the central and peripheral organs of the immune system in ISIAH rats and control
      WAG rats. In ISIAH rats, 24-h illumination for 14 days led to more pronounced
      inhibition of cell proliferation and differentiation in the thymus and more
      pronounced decrease in splenocyte proliferation and T and B cell counts in the
      spleen in comparison with WAG rats; however, the level of antigen-presenting
      cells in the spleen of ISIAH increased. We concluded that ISIAH rats are more
      sensitive to abnormal illumination regimen than WAG rats. Twenty-four-hour
      illumination was associated with impairments of central differentiation of T
      cells and activation of systemic inflammation followed by impairment of
      differentiation regulation, which can aggravate metabolic dysfunctions in these
      animals. 

PMID- 24288734
TI  - In vitro expression of IL-1alpha, GM-CSF, and TNF-alpha by multinucleated
      macrophages from BCG-infected mice.
AB  - Peritoneal cells from intact and BCG-infected mice were explanted in vitro. In
      these cultures, multinucleated macrophages in different number of nuclei were
      formed. The intensity of multinucleated cell formation was higher in cultures
      from BCG-infected mice. Increasing role of amitosis in the formation of
      multinucleated macrophages with relatively high number of nuclei was noted with
      presumable domination of cell fusion mechanism. Relatively high level of IL
      1alpha expression was noted only in the population of binucleated macrophages of
      BCG-infected mice in comparison with mononuclear cells. It was found macrophages
      from BCG-infected mice demonstrate a kind of "lineage commitment" towards
      multinucleated cells, which manifested in culture in initially high and
      increasing (with increasing the number of nuclei in cells) expression of
      granulocyte-macrophage CSF and TNF-alpha as well as initially high amitotic
      activity of macrophages.

PMID- 24288735
TI  - Expression profile of inflammatory breast cancer.
AB  - Inflammatory breast cancer is characterized by high malignancy, early and rapid
      lymphogenic and hematogenic metastasizing, and high mortality. The diagnosis of
      this form of cancer is based fully on the clinical criteria. Whole transcriptome
      analysis of tumor tissue specimens from patients with inflammatory breast cancer
      detected 137 differentially expressed mRNA (17 genes with low expression and 120
      with high expression). Genes involved in the organization of inflammatory
      process, chemotaxis, and transcription regulation were active in the process of
      pathogenesis of inflammatory breast cancer. 

PMID- 24288736
TI  - Study of antitumor activity of antibodies to TNF-alpha on Walker carcinosarcoma
      model.
AB  - The effect of release-active antibodies to TNF-alpha (Artrofoon) on the
      development of Walker carcinosarcoma 256 was studied in Wistar rats. Intragastric
      dose of this drug significantly inhibited the growth of tumor node (55%
      inhibition of tumor growth), but less effectively than the reference drug
      cyclophosphamide (80%). The studied drug significantly prolonged animal' lifespan
      (+97%) and its efficiency in this respect was comparable to that of
      cyclophosphamide (+96%). 

PMID- 24288737
TI  - Role of xenobiotic metabolism enzyme gene polymorphism in the formation of
      chemotherapy resistance in patients with chronic lymphoproliferative diseases.
AB  - Enzymes of the cytochrome P450 and GSTP1 families play a pivotal role in the
      metabolism of a wide variety of antitumor drugs and polymorphisms of genes
      encoding for metabolizing enzymes can affect drug efficacy and toxicity. We
      studied the associations between functionally significant gene polymorphisms
      CYP2C8, CYP2C9, CYP2C19, CYP3A5, and GSTP1 and clinical response to chemotherapy
      in patients with chronic lymphoproliferative diseases. Significant correlations
      with chemotherapy resistance were observed for CYP2C8 3 (OR=7.05; CI 95%=1.76
      29.55) and CYP2C9 2 polymorphisms (OR=4.1; CI 95%=1.03-16.81). No significant
      association between chemotherapy resistance and other examined polymorphisms were
      found.

PMID- 24288738
TI  - Changes in the retina in induced hypoestrogenia (according to optical coherent
      tomography data).
AB  - Ultrastructural changes in the retina under conditions of experimental
      hypoestrogenia were studied. Hypoestrogenic status was induced in female rabbits
      by extirpation of both uterine horns with appendages. Clinical status of the eyes
      was evaluated after 9 months by ophthalmoscopy and optical coherent tomography.
      Changes in the retinal layers under conditions of experimental estrogenia were
      detected: thickened retinal pigmented epithelium layer, a lesser layer of nerve
      fibrils, and thinning of the choriocapillary layer. A relationship between
      thinning of the choroid and thickening of the pigmented epithelium of the retina
      was detected. 

PMID- 24288739
TI  - Analysis of purine metabolites in maternal serum for evaluating the risk of
      gestosis.
AB  - Metabolome analysis of the serum from pregnant patients aimed at detection of low
      molecular-weight biomarkers of gestation process disorders indicated a
      relationship between the metabolic profile of maternal serum and risk of
      gestosis. In women with pre-eclampsia or preterm delivery, analysis of serum
      purine metabolites revealed changes in the metabolite concentrations, associated
      with pregnancy complications. 

PMID- 24288740
TI  - Effect of gold nanoparticles coated with plasma components on ADP-induced
      platelet aggregation.
AB  - We studied the effect of gold nanospheres coated with components of autologous
      blood plasma on ADP-induced platelet aggregation. Gold nanoparticles in the
      chosen concentration range (5-40 MUM) and particle size (5-30 nm) with or without
      coating produced no activating effect on platelet aggregation caused by
      aggregation inductor ADP in all applied doses (1.6, 2.0, and 5.0 MUM).
      Nanoparticles with a diameter of >60 nm inhibited platelet aggregation. These
      findings and published data confirm the biological safety of gold nanoparticles
      for targeted delivery of drugs and phototherapy.

PMID- 24288741
TI  - Stimulatory effect of volatile urinary components from intact mice on the
      proliferative activity of splenic lymphoid tissue in irradiated animals.
AB  - Immunohistochemical and morphometric analyses have demonstrated long-distance
      stimulatory effects of the natural volatile components of the urine of intact
      mice on the proliferation of splenic lymphocytes in mice exposed to a single
      total gamma-irradiation in a dose of 1 Gy. These results are in line with the
      data on stimulation of the humoral immune response to thymus-dependent antigen in
      irradiated mice exposed to urine specimens of intact animals. 

PMID- 24288742
TI  - Structural changes in the myocardium and serum lipid spectrum in experimental
      hypercholesterolemia and hypothyroidism.
AB  - We studied the peculiarities of lipid spectrum of the blood and structural
      reorganization of the myocardium in experimental hypercholesterolemia with and
      without hypothyroidism. It was found that alimentary hypercholesterolemia
      accompanied by elevated total cholesterol, LDL, HDL, and triglyceride
      concentrations led to a decrease in body weight, heart weight, number of
      cardiomyocytes in the heart and induced pronounced lytic changes in
      cardiomyocytes, circulation disorders (sludge syndrome, echinocytosis of
      erythrocytes, lymphostasis), diffuse fibrosis of the stroma, and appearance of
      foam cells among diffuse mononuclear infiltrate cells. The combination of
      hypercholesterolemia with hypothyroid status caused more pronounced changes in
      the lipid spectrum and atherogenic index and more pronounced lytic and
      necrobiotic changes in cardiomyocytes. These findings suggest that elevated
      cholesterol concentrations in the blood, especially against the background of
      suppressed thyroid function, can directly induce considerable damage to
      cardiomyocytes, intramural vessels, and erythrocytes without the development of
      myocardial ischemia and in the absence of atherosclerotic plaques. 

PMID- 24288743
TI  - Histophysiology of the immune system of Wistar rats at delayed terms after
      ovariectomy.
AB  - We studied histophysiological changes in organs of the immune system, liver, and
      lungs of Wistar rats at delayed terms after ovariectomy. On day 52 after surgical
      castration leading to a decrease in estradiol, progesterone, and testosterone
      levels, activation of the immune system was revealed characterized by stage I
      accidental thymus involution, while pulp depletion in the spleen, and enhanced IL
      2 and IFN-gamma production. We also observed small-droplet degeneration of
      hepatocytes and reactive changes in the lungs manifested in increased number of
      neutrophils in the interalveolar septa. 

PMID- 24288744
TI  - Effects of low-dose dichlorodiphenyltrichloroethane on the morphology and
      function of rat thymus.
AB  - The effect of low-dose dichlorodiphenyltrichloroethane on the function of the
      immune system is a serious problem because of wide use of this pollutant. We
      studied the morphological and functional changes in the thymus of rats receiving
      low-dose dichlorodiphenyltrichloroethane for 6 and 10 weeks. Histological studies
      detected changes characterized by lymphocyte and reticuloepitheliocyte death,
      progressing with increase of dichlorodiphenyltrichloroethane dose, and a decrease
      of the thymocyte proliferative activity. The results of comparative analysis of
      changes in the thymuses of rats in experimental and control groups during
      different periods of the study indicated that low-dose
      dichlorodiphenyltrichloroethane promoted earlier onset of age-specific involution
      and caused a dose-dependent acceleration of these changes. 

PMID- 24288745
TI  - Effect of peripheral D2 dopamine receptor antagonist domperidone on metabolism,
      feeding behavior, and locomotor activity of rats.
AB  - We studied the possibility of activation of the central dopaminergic system
      compartment by modulating activity of D2 dopamine receptors in the
      gastrointestinal tract with domperidone, an antagonist not crossing the blood
      brain barrier. Intragastric administration of 0.1 mg/kg domperidone to rats was
      followed by a significant decrease in feeding behavior and stimulation of basal
      metabolism, but had no effect on locomotor activity of animals in a Phenomaster
      system. These effects are typical of psychostimulant agents that stimulate
      dopamine release from nerve endings in the nucleus accumbens and some regions of
      the brain cortex. Our results indicate that physiological functions associated
      with activity of the central dopaminergic system can be modulated through
      peripheral dopamine receptors.

PMID- 24288746
TI  - Age-related peculiarities of inotropic response of rat myocardium to selective
      block of M1-cholinoreceptors.
AB  - In vitro effect of M1-cholinoreceptor blockade on the cardiac inotropic function
      was examined in rats aging 1, 3, 6, 8, and 20 weeks. In 1- and 3-week old rat
      pups, the sympathetic control of the heart has not developed, the age of 7-8
      weeks being pubertal. Adult 20-week rats were used as the controls. In rats of
      all age groups, preliminary blockade of M1-cholinoreceptors did not prevent the
      inhibitory effect of carbacholine on contractility of the atrial and ventricular
      myocardium. The inhibitory effect of pirenzepine on the contractile force of
      ventricular myocardium was revealed in 6-week rats. 

PMID- 24288747
TI  - Effect of prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)
      cyanopyrrolidine on activity of proline-specific peptidases in brain structures
      of rats with experimental MPTP-induced depressive syndrome.
AB  - A noncompetitive synthetic inhibitor of prolyl endopeptidase benzyloxycarbonyl
      methionyl-2(S)-cyanopyrrolidine (1.0 mg/kg intraperitoneally for 2 weeks)
      prevented the increase in activity of prolyl endopeptidase in the frontal cortex,
      striatum, and hypothalamus and activation of dipeptidyl peptidase IV in the
      frontal cortex of rats with experimental dopamine deficiency-dependent depressive
      syndrome caused by administration of proneurotoxin MPTP (2 weeks). Our results
      suggest that the antidepressive effect of prolyl endopeptidase inhibitor is at
      least partly related to prevention of enzyme activation in the frontal cortex.
      The antistress effect of this substance can be associated with prevention of
      enzyme activation in the hypothalamus. 

PMID- 24288748
TI  - Correlation between antibodies to gonadotropin-releasing hormone and reproductive
      disorders in humans.
AB  - Antibodies (IgG) to gonadotropin-releasing hormone were measured by ELISA in
      blood serum of women with miscarriage and men with infertility. Spontaneous
      production of antibodies to gonadotropin-releasing hormone was observed during
      miscarriage and male infertility: the mean level of antibodies in these groups
      was higher than in healthy women and men (p<0.0001). ROC-analysis showed that
      test for IgG to gonadotropin-releasing hormone has high sensitivity, specificity,
      and AUC (more that 70%, 90%, and 0.8, respectively). Thus, the presence of
      antibodies to gonadotropin-releasing hormone was associated with impairments of
      human reproductive function. 

PMID- 24288749
TI  - Lipid spectrum in patients with atherosclerosis of various localizations.
AB  - Variants of dyslipidemias were studied in 78 patients with atherosclerosis of
      various localizations. We also studied HDL content and atherogenic index, which
      served as a predictor of polyvascular disease. Depending on localization
      atherosclerosis had specific features. Type II of dyslipidemia was typical for
      multifocal and coronary atherosclerosis, type IV was typical for brachiocephalic
      arteries. 

PMID- 24288750
TI  - Role of NF-kappaB-dependent signaling in the realization of growth potential of
      mesenchymal progenitor cells in vitro.
AB  - Signal pathways of realization of growth potential of mesenchymal progenitor
      cells related to transcription factor NF-kappaB were studied in vitro. NF-kappaB
      was found to participate in the proliferation and differentiation of progenitor
      elements that can be blocked by its specific inhibitor oridonin. NF-kappaB
      inhibitor aurothiomalate had no effect on the functions of fibroblastic CFU. 

PMID- 24288751
TI  - Bezafibrate causes depression of the immune response and increases the
      sensitivity to endotoxin in association with low level of HDL and PPARalpha
      activity in hypertensive ISIAH rats.
AB  - We studied the effect of bezafibrate on hepatic PPARalpha activity and immune
      parameters in hypertensive ISIAH rats in comparison with normotensive WAG rats
      under conditions of LPS treatment. Bezafibrate increased activity of PPARalpha in
      WAG rats, but not in ISIAH rats. As differentiated from WAG rats, bezafibrate
      produced a potent effect on the content of T cell subpopulations in the thymus
      and spleen of ISIAH rats. Administration of LPS after injection of bezafibrate
      caused death of 50% ISIAH animals (but not WAG rats), which was associated with
      low level of HDL cholesterol and increased triglyceride content. Our results
      suggest that the hypolipidemic treatment (e.g., bezafibrate) can increase the
      severity of complications in patients with infectious and inflammatory diseases
      in association with low level of HDL.

PMID- 24288752
TI  - Changes in contractile activity of the large intestine in rabbits during the
      poststress period before and after blockade of muscarinic and nicotinic
      receptors.
AB  - The rabbits were exposed twice to stress, fixation to a frame in the supine
      position, for 60 min. Contractile activity of all portions of the large intestine
      was shown to increase significantly during the poststress period. These changes
      were not observed under conditions of blockade of muscarinic and nicotinic
      receptors. This state can be considered as dyskinesia impairing large intestinal
      transit of chyme. 

PMID- 24288753
TI  - CYP2E1 gene promoter polymorphism -1293G>C increases the risk of essential
      hypertension in men with alcohol abuse.
AB  - We studied the association between of cytochrome P450 2E1 (CYP2E1) gene
      polymorphism and risk of essential hypertension development depending on alcohol
      drinking habit in unrelated men in Russian population (patients with essential
      hypertension and healthy volunteers). All participants were genotyped for four
      CYP2E1 gene polymorphisms -1293G>C (rs3813867), -1053C>T (rs2031920), 7632T>A
      (rs6413432), and 9896C>G (rs2070676) by PCR and restriction analysis. We found
      statistically significant associations between -1293C allele (OR=5.04, 95%
      CI=1.23-20.70, p=0.03) and -1293GC genotype (OR=5.36, 95% CI=1.28-22.50, p=0.03)
      with increased risk of essential hypertension in men. Stratified analysis on
      alcohol drinking habit showed that the presence of -1293C allele (OR=6.82, 95%
      CI=1.12-41.70, p=0.04) and -1293GC genotype (OR=7.61, 95% CI=1.2-48.4, p=0.03) in
      men with alcohol abuse increases the risk of essential hypertension. The obtained
      data suggest that excessive alcohol consumption and increased induction of
      cytochrome in the carriers of -1293C allele of CYP2E1 gene lead to generation of
      highly reactive free radical oxidation products. These processes induced
      oxidative stress and endothelial induction, which served as the pathogenetic
      basis for essential hypertension.

PMID- 24288754
TI  - Apolipoprotein A-I as a carrier of lipopolysaccharide into rat hepatocytes.
AB  - Apolipoprotein A-I-mediated transport of LPS into isolated rat hepatocytes was
      demonstrated by means of fluorescent microscopy and spectrofluorometry. The
      efficiency of intracellular endotoxin transport in a complex with apolipoprotein
      A-I significantly exceeded the absorption of LPS without this carrier. Our
      results suggest that the mechanism of the anti-inflammatory effect of HDL and
      apolipoprotein A-I can be related to alternative pathway for metabolic
      degradation of this endotoxin with the involvement of lipoprotein receptors. 

PMID- 24288755
TI  - Biodistribution of rhenium cluster complex K4[Re6S8(CN)6] in the body of
      laboratory rats.
AB  - We studied the biodistribution of luminescent octahedral rhenium cluster complex
      K4[Re6S8(CN)6], a promising agent for photodynamic therapy. It was shown that
      rhenium complex [Re6S8(CN)6](4-)is mainly accumulated in the liver, the central
      organ of metabolism, and can be excreted by the kidneys. The cluster complex was
      also accumulated in the spleen in significant amount, which makes it a promising
      agent for creation of preparations for diagnostics and treatment of
      lymphoproliferative disorders. The mean lethal dose of the cluster complex was
      0.38 g/kg. 

PMID- 24288756
TI  - Energy metabolism and biochemical features of adipose tissues in ICR mice after
      long-term calorie-restricted diet.
AB  - Long-term calorie-restricted diet (8 weeks, 60% of control food intake) was
      followed by an increase in thermogenic activity of interscapular brown fat. The
      relative amount of DNA and protein and the rate of oxygen consumption increased
      and tissue-specific marker of brown fat (uncoupling protein UCP1) appeared in
      significantly reduced deep-pink abdominal adipose tissue. 

PMID- 24288757
TI  - Effect of cation type and concentration of nitrates on neurological disorders
      during experimental cerebral ischemia.
AB  - Experiments were performed on the model of ischemic stroke due to bilateral
      occlusion of the carotid arteries. Nitrates had various effects on the dynamics
      of neurological disorders and mortality rate of Wistar rats, which depended on
      the cation type and concentration. 

PMID- 24288758
TI  - Effects on alimentary high-fat diet on thiol disulfide homeostasis in rats.
AB  - The effects of high-fat diet on the thiol disulfide homeostasis of rats were
      evaluated by activities of glutathione redox system functioning in the blood and
      liver. A short-term (30 days) high-fat diet inhibited activities of glutathione
      dependent enzymes. High-fat loading for 90 days promoted the development of a
      compensatory response of the glutathione redox system and restoration of the
      thiol disulfide homeostasis. The compensatory processes in the glutathione system
      failed on day 180 of alimentary loading because of redox imbalance in the thiol
      disulfide metabolism. 

PMID- 24288759
TI  - A method of low-temperature storing of agarose slides with lysed cells.
AB  - A method has been developed for a long-term low-temperature storage (-10 to -15
      degrees C) of the agarose slides with nucleoids (lysed eukaryotic cells). After
      lysis of agarose-immobilized cells, the slides were incubated for 30 min in
      phosphate buffer with 50% glycerol and 100 mM EDTA, thereupon they were stored in
      a freezer at -10 to -15 degrees C. After long-term storage, the slides were re
      incubated for 30 min in lysing solution. The measurements of the baseline and in
      vitro induced DNA damage in nucleoids of the human and mouse leukocytes, which
      had been stored in agarose slides at low temperature, showed that DNA damage
      level determined after a 40-day storage did not significantly differ from that of
      the fresh slides. The advanced storage method is simple and reliable; it opens
      the way to avoid cryopreservation of the biological samples and to process little
      by little a great number of the identically prepared slides.

PMID- 24288760
TI  - On the mechanism of anti-ischemic effects of afobazole.
AB  - The anti-ischemic effect of synthetic and pharmacologically tested anxiolytic
      afobazole (10 mg/kg intravenously) was studied on anesthetized rats with acute
      endocardial ischemia caused by isoproterenol infusion (20 mg/kg/min). A calcium
      antagonist verapamil (1 mg/kg intravenously) belonging to the group of phenyl
      alkyl amine derivatives was used as the reference drug. Afobazole and verapamil
      were shown to exhibit anti-ischemic activity in this experimental model, which
      was seen from significant decrease in ST segment depression on ECG. The
      neuroprotective effect of afobazole is to a great extent related to its affinity
      for sigma1 receptors. Therefore, a special series was performed to evaluate the
      anti-ischemic effect of afobazole after blockade of these receptors with
      haloperidol (0.5 mg/kg intravenously). Afobazole exhibited no anti-ischemic
      activity under these conditions. sigma1 receptor blockade had no effect on anti
      ischemic activity of verapamil. Our results suggest that the agonistic effect of
      afobazole on sigma1 receptors in cardiomyocytes contributes to anti-ischemic
      activity of this agent.

PMID- 24288761
TI  - Polymeric complexes of isonicotinic acid hydrazide with antituberculosis effects.
AB  - We studied the effects of an analogue of isonicotinic acid hydrazide on the
      treatment course of experimental tuberculosis. Complex analysis has demonstrated
      the efficiency of isonicotinic acid hydrazide immobilized on a carrier that
      consisted of water-soluble cation-active analogue of chitosan (N
      chlorohydroxypropyl chitosan) in a complex with cobalt ions in the therapy of
      experimental tuberculosis. Immunostimulating activity of the polymeric metal
      complex was revealed. The obtained data can be used for the development of highly
      effective methods for tuberculosis treatment. 

PMID- 24288762
TI  - Effects of flavonoid-containing preparation Extralife on hydrogen peroxide
      production and functioning of mitochondrial ATP-dependent potassium channel.
AB  - Extralife, a Pentaphylloides fruticos extract, in concentrations of 0.005-10
      MUg/ml dose-dependently increased H2O2 production in rat heart mitochondria in
      the presence of respiration substrates. Extralife decreased ATP-induced
      accumulation of H2O2 related to inhibition of mitochondrial ATP-dependent
      potassium channel. This effect was observed only at low doses of the adaptogen
      (0.05-3 MUg/ml). High doses of the substance (5-10 MUg/ml) did not abolish ATP
      dependent production of H2O2 and increased the rate of H2O2 generation by the
      mitochondria. We concluded that Extralife in trace concentrations could activate
      mitochondrial ATP-dependent potassium channel and decrease H2O2 accumulation in
      the mitochondria.

PMID- 24288763
TI  - Single intravenous injection of coenzyme Q10 protects the myocardium after
      irreversible ischemia.
AB  - Experiments were performed on the model of irreversible myocardial ischemia in
      Wistar rats. Coenzyme Q10 was injected intravenously 10 min after coronary artery
      occlusion. On day 21 after myocardial infarction the content of coenzyme Q10 in
      the left ventricle, liver, and plasma from animals of the treatment group was
      higher than that in untreated rats by 23, 1042, and 87%, respectively (p<0.05).
      The area of the necrotic zone was lower, and postinfarction hypertrophy of the
      left ventricle was less pronounced in coenzyme-receiving rats. Right ventricular
      hypertrophy did not develop in these animals. These rats were characterized by
      greater stroke volume (by 24.6%, p<0.05), stroke work (by 34.9%), cardiac output
      (by 37.8%, p<0.05), ejection fraction (by 35.7%, p<0.05), and contractility (by
      22.5%, p<0.05), but lower end-diastolic pressure (by 25.8%, p<0.05) than
      untreated animals. These data indicate that the development of parenteral
      ubiquinone preparations holds much promise for urgent therapy of acute
      cardiovascular disorders.

PMID- 24288764
TI  - Antithrombogenic activity of antioxidant compounds.
AB  - Antithrombotic activities of enoxifol, a new antioxidant with antiaggregant
      activity demonstrated in vitro and in vivo, and antioxidant mexidol were compared
      on the rat model of arterial thrombosis induced by application of 50% ferric
      chloride. Acetylsalicylic acid (antiaggregant) served as the reference drug. All
      drugs exhibited dose-dependent antithrombotic activity. Enoxifol was more
      effective than mexidol, both drugs being more active than the reference drug
      (acetylsalicylic acid). Taking into account the pathogenesis of the thrombosis in
      this experimental model, we can hypothesize that the pronounced antithrombotic
      effect of enoxifol was due to its antiaggregant and antioxidant activities. 

PMID- 24288765
TI  - Lipid imbalance in individuals predisposed to rheumatoid arthritis: possible
      relationship with common infections.
AB  - Lipid balance was studied in female patients with late rheumatoid arthritis,
      their healthy female relatives liable to autoimmune diseases, and healthy women
      without family history of autoimmune diseases. Previous studies showed that the
      relatives of patients with rheumatoid arthritis suffered from frequent stubborn
      common infections, which prompted us to analyze the relationship between lipid
      metabolism and the infectious syndrome parameters. Blood serum and cells were
      collected for analysis when females had no clinical symptoms of infections (in
      all groups) or laboratory signs of inflammatory process (in the relatives and
      controls). Proatherogenic shifts in serum lipid composition presumably associated
      with frequent lasting infections were detected in individuals liable to
      rheumatoid arthritis development. Elevated cholesterol content in mononuclear
      leukocytes in this group could lead, in turn, to dysfunctions of these cells and
      augment the defects of anti-infection defense. The parameters of lipid balance in
      patients with late rheumatoid arthritis were close to the age-specific norm. 

PMID- 24288766
TI  - Immunomodulating effect of ethyl pyruvate on nonsyngenic transplanted tumor in
      mice.
AB  - Indolamine-2,3-dioxygenase, a tryptophan-catabolizing enzyme, creates local
      conditions suppressing immune lymphocytes. Expression of this enzyme in tumors
      protects them from immune mechanisms, while its inhibition partially reduces
      tumor immunoresistance. This effect is attained by multiple subcutaneous or
      intraperitoneal injections of ethyl pyruvate, an indolamine-2,3-dioxygenase
      inhibitor. Experiments on mouse nonsyngenic tumor have demonstrated the
      immunomodulating effect of chronic oral ethyl pyruvate administered with drinking
      water.

PMID- 24288767
TI  - Effects of multiwalled carbon nanotubes received orally during 6 days on the
      gastrointestinal tract.
AB  - The effects of multiwalled carbon nanotubes on epitheliocytes of different
      compartments of the gastrointestinal tract and urothelium of different
      compartments of the renal nephron were studied in CBA mice. The nanotubes
      affected mouse gastrointestinal mucosa and renal urothelium. The cell reaction in
      the macula densa of the renal distal tubules and the immune system reaction to
      oral nanotubes were detected. A possible effect of nanotubes administered orally
      on the renal filtration function was hypothesized. 

PMID- 24288768
TI  - Signs of cell-cell interactions in sarcoma 45 tissue under conditions of
      antitumor effect caused by injection of magnetite nanoparticles.
AB  - Changes in transplanted sarcoma 45 tissue in outbred albino rats with tumor
      regression under the effect of magnetite nanoparticles (magnetic fluid) were
      studied by light and electron microscopy. The ultrastructure and cell death types
      in regressing tumors and signs of cell-cell interactions with participation of
      macrophages, lymphocytes, neutrophils, and degranulating mast cells were
      described. Some possible mechanisms of a pronounced antitumor activity of
      magnetite nanoparticles were discussed. 

PMID- 24288769
TI  - Immunohistochemical study of alpha- and beta-cell distribution in human
      pancreatic Langerhans islets of various types.
AB  - Various types of insulin- and glucagon-containing endocrine cell distribution
      were found by double staining with antibodies to insulin and glucagon in the
      pancreatic autopsy material from subjects without carbohydrate metabolism
      disorders. The cell composition of the islets and their morphogenetic maturity
      depended on the vascularization degree. Insulin-containing cells predominated in
      small clusters of endocrine cells and in islets with few capillaries, while
      glucagon predominated in large islets with rich vascularization. A scheme of
      development and differentiation of Langerhans islets in the adult human pancreas
      was presented. 

PMID- 24288770
TI  - Paleoamygdala and biogenic amines: effect of gender factor and sex steroid
      content on their content and metabolism.
AB  - The content of biogenic amines and their metabolism in the ancient part of the
      amygdala (paleoamygdala) differ in male and female rats and depended on the phase
      of the estrous cycle. 

PMID- 24288772
TI  - Experimental study of the diagnostic potentialities of bioimpedance measurement
      in acute intestinal obstruction.
AB  - The dynamics of impedance values of the small and large intestine, parietal
      peritoneum, and greater omentum was analyzed during different periods of
      experimental acute intestinal obstruction. The impedance was below the normal,
      which indicated progressive microcirculatory disorders and necrosis of the
      intestinal wall. The histomorphological picture of healing of anastomoses created
      after resection of the intestine with consideration for bioimpedance values and
      of anastomoses created after resection of the intestine in a priori viable
      tissues virtually did not differ. 

PMID- 24288771
TI  - Memory disorders in rats after impairment of the dorsal hippocampal CA3 field
      with kainic acid.
AB  - We studied the possibility of conditioning of food-procuring response in animals
      after impairment of the dorsal hippocampal region with kainic acid. Histological
      studies of brain sections showed that the greater part of dorsal hippocampal CA3
      pyramidal neurons were lyzed in 2 weeks after kainic acid microinjection into the
      hippocampus. Morphological signs of necrosis were found in CA2 and CA4 neurons at
      the interface with CA3 field. Preinjection of anti-inflammatory cytokine IL-10
      virtually did not prevent neuronal death. Damage to the hippocampus impaired
      learning of experimental animals and they required more attempts for reliable
      performance of the skill than the controls. Short-term memory of experimental
      rats was retained, which was proven by the results of single-day training. It was
      hypothesized that memory dysfunctions in animals after damage to the dorsal
      hippocampal CA3 field and to the hippocampus in general are determined by
      impaired transition of short-term into long-term memory. 

PMID- 24288773
TI  - Mass-spectrometric monitoring of anesthesia adequacy.
AB  - Anesthesia adequacy was assessed with mass-spectrometric method by monitoring the
      ratio of mass concentrations of end-tidal CO2 and inhaled O2 in every respiratory
      cycle during surgery. For real-time monitoring, we used a mass spectrometer with
      electron ionization connected to the respiratory contour of inhalation anesthesia
      machine. The study has demonstrated advantages of the novel method in real-time
      assessment of adequacy of the total intravenous anesthesia.

PMID- 24288774
TI  - Experimental reproduction of stages of the respiratory distress syndrome.
AB  - The authors present a method for experimental reproduction of stages of the acute
      respiratory distress syndrome development, including the initial stage - acute
      pulmonary injury. Concentrated neutrophil transmitters served as the factor
      triggering the development of the process. The adequacy of the model was
      confirmed by the clear-cut morphological stages of the process. The possibility
      of reproducing the syndrome by injection of concentrated neutrophil transmitters
      confirmed their leading role in impairment of the alveolar capillary membrane. 

PMID- 24288775
TI  - Estimation of efficiency of solvent-detergent method for virus inactivation in
      the technology of immunoglobulin production on the model of duck hepatitis B
      virus.
AB  - The virucidal action of solvent tributyl phosphate and detergent sodium cholate
      used in the production of immunoglobulin for inactivation of viruses with lipid
      envelope was studied on the model of duck hepatitis B virus. PCR analysis
      revealed no significant decrease in duck hepatitis B virus DNA concentrations
      after treatment with solvent/detergent. At the same time, in vivo experiments
      showed that treatment of duck hepatitis B virus with tributyl phosphate
      (concentration >0.15%) and sodium cholate (concentration >0.1%) at 37 degrees C
      for 6 h or longer completely inactivated this model virus added to immunoglobulin
      solution in concentration 5 log ID50. Duck hepatitis B virus appears to be one of
      the most acceptable model viruses for validation of virus inactivating
      technologies in manufacturing human plasma preparations. 

PMID- 24288776
TI  - Optimal aging through research. Abstracts of the 66th Annual Meeting of
      Gerontological Society of America. November 20-24, 2013. New Orleans, Louisiana,
      USA.

PMID- 24288777
TI  - Abstracts of the British Thoracic Society Winter Meeting.. December 4-6, 2013.
      London, United Kingdom.

PMID- 24288778
TI  - Editorial: an inaugural message for the IEEE Journal of Biomedical and Health
      Informatics.

PMID- 24288779
TI  - Abstracts of Advances in Inflammatory Bowel Diseases Crohn's & Colitis
      Foundation's Clinical & Research Conference. December 12-14, Hollywood, Florida,
      USA.

PMID- 24288780
TI  - Synthesis, analytical analysis, and medicinal aspect of novel benzimidazoles and
      their metal complexes.
AB  - Benzimidazole and their metal analogs that can act as multimodal agent and have
      non-peptidic CCK-B receptor antagonist were synthesized and characterized on the
      basis of spectroscopic techniques such as FT-IR, NMR, FAB-MS and also evaluated
      for biologic efficacy. The ligands showed binding to most of the organs, known to
      express CCK receptors in biodistribution studies. Cholecystokinin (CCK1 and CCK2)
      receptor binding affinities of these analogs (IC50) are 0.802 +/- 0.007 for
      compound C and 0.326 +/- 0.012 for compound D in rat pancreatic acini. These
      studies have provided a new template for further development of novel agents for
      various related diseases.

PMID- 24288781
TI  - Abstracts of the 11th Annual Meeting of the Japanese Society of Medical Oncology.
      August 29-31, 2013. Sendai, Japan.

PMID- 24288782
TI  - Response to "A new exercise central hemodynamics paradigm: time for reflection or
      expansion"?

PMID- 24288783
TI  - Response to "Does atrial fibrillation affect the automated oscillometric blood
      pressure measurement"?

PMID- 24288784
TI  - Response to "Are aldosterone levels inappropriately low in preeclampsia"?

PMID- 24288785
TI  - Reply: To PMID 23665729.

PMID- 24288786
TI  - NZNO professional services manager Susanne Trim responds.

PMID- 24288787
TI  - Ex-president guilty of professional misconduct.

PMID- 24288788
TI  - Shared regulatory body unlikely.

PMID- 24288789
TI  - Promoting Maori nursing clinical leadership.

PMID- 24288790
TI  - Legislative changes 'bad for nurses and patients'.

PMID- 24288791
TI  - Equal pay decision a 'turning point'.

PMID- 24288792
TI  - DHB stopworks raise awareness.

PMID- 24288793
TI  - Primary health care: Te Rau Kokiri ratified.

PMID- 24288794
TI  - Aged care: mediation underway at Ranfurly.

PMID- 24288795
TI  - Disillusioned graduate.

PMID- 24288797
TI  - E-health for better communication.

PMID- 24288798
TI  - An overview of the aged care workforce supplement.

PMID- 24288800
TI  - Delayed cord clamping benefits babies.

PMID- 24288799
TI  - Painkillers a potential health risk.

PMID- 24288801
TI  - The due diligence on the ESRD payment cut.

PMID- 24288802
TI  - Reflections.

PMID- 24288803
TI  - [Presenteeism: attending work while sick].

PMID- 24288804
TI  - The American Academy of Orthopaedic Surgeons evidence-based guideline on:
      treatment of osteoarthritis of the knee, 2nd edition.

PMID- 24288805
TI  - Contemporary management of metastatic bone disease: tips and tools of the trade
      for general practitioners.

PMID- 24288806
TI  - Ultrastructure of the sexually dimorphic tarsal glands and tegumental glands in
      gonyleptoid harvestmen (Opiliones, Laniatores).
AB  - In at least four closely related families of the diverse harvestmen lineage
      Gonyleptoidea, males may possess sexually dimorphic tarsal glands in the swollen
      tarsomeres of the basitarsus and/or metatarsus of leg I. The first histological
      and ultrastructural examination of the sexually dimorphic tarsal glands in leg I
      focused only on Manaosbiidae. In this study, we examine the morphology and
      ultrastructure of the sexually dimorphic glands, and their associated glandular
      openings, found in the basitarsus and/or metatarsus of leg I of males
      representing Cosmetidae, Gonyleptidae, and Cranaidae (glandular openings only).
      In cosmetids and gonyleptids, the tarsal glands are made up of 20-60 glandular
      units that form distinct groups within the prolateral and retrolateral half of
      the tarsomere. Each glandular unit consists of a pair of terminal secretory
      cells, an intercalary cell wrapped around the receiving canal, and a canal cell
      tightly wrapped around the length of the conducting canal. Cosmetidae,
      Gonyleptidae, and Cranaidae exhibit remarkably similar tarsal glands and gland
      openings although the location of the glands in the leg differs slightly among
      them. Males of these three families exhibit markedly different glands and
      glandular openings compared to males of the family Manaosbiidae. The sexually
      dimorphic tarsal glands may provide an important morphological character for
      determining phylogenetic relationships among gonyleptoid families. Finally, we
      provide morphological and ultrastructural data for the common tegumental glands.
      These data indicate that the sexually dimorphic tarsal glands are strikingly
      similar to, and may possibly be derived from, the tegumental glands.

PMID- 24288807
TI  - Rita Levi-Montalcini: the story of an uncommon intellect and spirit.

PMID- 24288808
TI  - Looking at the future with Rita.
AB  - This paper on Rita Levi-Montalcini (1909-2012), who received in 1986 the Nobel
      Prize in Physiology or Medicine for the discovery of nerve growth factor, focuses
      on aspects of her advocacy and her commitment to education in which she has been
      especially active in the last part of her long life. With passionate confidence
      on the capabilities of the aging brain (together with severe admonition against
      the pursuit of immortality), she encouraged contributions of senior citizens to
      the society. Always projected into the future, with enduring faith in the
      potential of young individuals, in education as a key to development, in the
      capabilities of women, in the importance of gender equality, Rita established in
      2001 the Rita Levi-Montalcini Foundation for the education of African women. Her
      legacy on engagement for a better 'global village' should not be forgotten by the
      neuroscience community.

PMID- 24288809
TI  - PhiC31 integrase-mediated genomic integration and stable gene expression in the
      mouse mammary gland after gene electrotransfer.
AB  - BACKGROUND: PhiC31 integrase is capable of conferring long-term transgene
      expression in various transfected tissues in vivo. In the present study, we
      investigated the activity of phiC31 integrase in mouse mammary glands. METHODS:
      The normal mouse mammary epithelial cell line HC11 was transfected with FuGENE(r)
      HD Transfection Reagent (Roche Diagnostics, Shanghai, China). Transfection of the
      mouse mammary gland in vivo was performed by electrotransfer. Transgene
      expression was detected by western blotting and an enzyme-linked immunosorbent
      assay. Genomic integration and integration at mpsL1 was confirmed by a nested
      polymerase chain reaction. RESULTS: An optimal electrotransfer protocol for the
      lactating mouse mammary gland was attained through investigation of different
      voltages and pulse durations. PhiC31 integrase mediated site-specific transgene
      integration in HC11 cells and the mouse mammary gland. In addition, the site
      specific integration occurred efficiently at the 'hot spot' mpsL1. Co-delivery of
      PhiC31 integrase enhanced and prolonged transgene expression in the mouse mammary
      gland. CONCLUSIONS: The results obtained in the present study show that the use
      of phiC31 integrase is a feasible and efficient method for high and stable
      transgene expression in the mouse mammary gland.

PMID- 24288810
TI  - Retraction notice to "Two novel bioactive glucosinolates from broccoli (Brassica
      oleracea L. var. italica) florets" [Bioorg. Med. Chem. Lett. 22 (2012) 5555
      5558].

PMID- 24288811
TI  - Vitamin D: key to muscle and bone strength, independence.  A deficiency in
      vitamin D could impair your mobility and activities of daily living.

PMID- 24288812
TI  - Aspirin protects some hearts better than others. It's in the genes. A biomarker
      can predict a person's response to this potentially lifesaving medication.

PMID- 24288813
TI  - High fat levels in muscles, liver, blood, and bone marrow linked to poor bone
      health.  But a healthy weight and healthy diet can help stave off bone loss,
      osteoporosis.

PMID- 24288814
TI  - Control blood sugar levels to reduce risk of Alzheimer's.  Lifestyle
      modifications--diet and exercise--can help manage blood glucose.

PMID- 24288815
TI  - Breakthrough in ER+ breast cancer.  Specific gene's shutdown is detectable in
      blood; indicates cancer cell vulnerability, thus enabling earlier treatment.

PMID- 24288816
TI  - My lower back causes me a great deal of pain. Are there any non-pharmaceutical
      ways to deal with this? I'm afraid of becoming addicted to painkillers.

PMID- 24288817
TI  - I'm basically chained to my desk and computer all day long.  Do you have any tips
      on how I can break up all the sitting during the course of the day?

PMID- 24288818
TI  - My mother suffers from hearing impairment; does this put her at greater risk for
      Alzheimer's disease?

PMID- 24288819
TI  - Is there such a thing as too low a cholesterol level?

PMID- 24288820
TI  - When it comes to fats, what should I look for on an ingredients list?

PMID- 24288821
TI  - [Risk and sex factor on suicide among substance use disorder patients].

PMID- 24288822
TI  - [Current status and future prospect on molecular imaging for diagnosis and
      therapy].

PMID- 24288823
TI  - Authors' response.

PMID- 24288824
TI  - The authors respond.

PMID- 24288825
TI  - Diversity in veterinary  medicine.

PMID- 24288827
TI  - Horse head count: Kentucky survey helps state gauge impact of equine industry.

PMID- 24288826
TI  - Best in show: breeder and veterinarian cherished for building important
      connections.

PMID- 24288828
TI  - Heartworm preventive resistance is real.

PMID- 24288829
TI  - Saving pets through education: Dr. Stephen L. Jones is the 2013-2016 American
      Heartworm Society president.

PMID- 24288830
TI  - Investigations ongoing in dog illnesses, deaths.

PMID- 24288831
TI  - AHA certification covers nearly 1 billion farm animals.

PMID- 24288832
TI  - Assay to help identify PED-infected pigs.

PMID- 24288833
TI  - Cell, organ biotechnology center opening in Texas.

PMID- 24288834
TI  - In reply.

PMID- 24288835
TI  - [A tumor of the pancreatic head developing 7 years after the treatment of
      malignant lymphoma].

PMID- 24288836
TI  - Authors' reply.

PMID- 24288837
TI  - Authors' reply.

PMID- 24288838
TI  - Ventricular assist devices.

PMID- 24288839
TI  - Alpha omega alpha and scholarship.

PMID- 24288840
TI  - Wet dust.

PMID- 24288841
TI  - Yes, I can. Learning to cope with death.

PMID- 24288842
TI  - Food fight.

PMID- 24288843
TI  - Running toward the fire: empathy and ethics in medical education.

PMID- 24288844
TI  - Who killed lab rounds?

PMID- 24288845
TI  - Moving forward through collaboration, coordination, and communication.

PMID- 24288846
TI  - Mexican-American children's perspectives: neighborhood characteristics and
      physical activity in Texas-Mexico border colonias.
AB  - The qualitative study described in this article investigated perceptions about
      environmental factors influencing physical activity (PA) among children from
      underserved neighborhoods known as colonias in the U.S.-Mexico border. Ten focus
      groups were conducted with 67 Mexican-American colonia children ages 8 to 13
      living in one of the poorest border counties in the U.S. Analyses indicated that
      PA among children was influenced by neighborhood characteristics, including
      litter, speeding cars, unleashed dogs, and dark streets. The children also
      underlined intrapersonal and social environmental factors. Findings may inform
      policy makers and public health professionals about ways to promote PA among
      underserved children through urban planning and programs focusing on PA
      supportive infrastructure, neighborhood safety, and family- and home-based
      physical activities.

PMID- 24288847
TI  - Physical conditions of a house and their effects on measured radon levels: data
      from Hillsborough Township, New Jersey, 2010-2011.
AB  - Concentrations of radon in homes are thought to be dependent on several factors,
      including the presence of certain physical conditions of the house that act as
      entry points for this colorless, odorless gas. Drains and sump pits are currently
      sealed as part of radon mitigation, but doing so may cause drainage problems and
      mold. The authors attempted to determine if specific attributes and physical
      conditions of homes are associated with measured residential concentrations of
      radon. Radon tests were conducted in 96 participating homes in rural Hillsborough
      Township, New Jersey, November 2010-February 2011. Samplers were placed and a
      walk-through survey was conducted. Test devices were analyzed by a New Jersey
      certified radon testing laboratory and results compared to survey data. Overall,
      50% of houses with a perimeter drain and 30% of houses with a sump pit exceeded
      the New Jersey and federal radon action level of 4.0 picocuries per liter, and
      47% of homes with both a sump and a perimeter "French" drain exceeded this action
      level. The authors' results suggested certain physical conditions act as pathways
      allowing radon entry into homes. Results could be used by local and state
      agencies to start local initiatives, e.g., increased testing or to seal these
      components as partial mitigation.

PMID- 24288848
TI  - Residential carbon monoxide (CO) poisoning risks: correlates of observed CO alarm
      use in urban households.
AB  - The authors conducted a household survey and observation to assess carbon
      monoxide (CO) knowledge and risks as well as prevalence of CO alarms in an urban
      community prior to the enactment of a mandatory ordinance requiring CO alarms in
      one U.S. city. From July to December 2009, household surveys and observations
      were completed in 603 residences. Participants were mostly African-American
      (61%), women (70%), 25-54 years in age (66%), and with a high school education or
      less (51%). Most homes visited contained CO-producing appliances, including gas
      stoves (86%), gas furnaces (82%), and gas water heaters (79%). Participants'
      overall mean percentage correct knowledge score was 57%. CO alarms were reported
      by 33% of participants and observed among 28% of households. Low rates of CO
      knowledge and CO alarm ownership, combined with high rates of CO-producing
      sources in homes, suggests the need for widespread campaigns to promote CO
      alarms. Recommendations are also made to integrate the lessons learned from the
      public health community's experience promoting smoke alarms.

PMID- 24288849
TI  - Multilevel analysis of childhood nonviral gastroenteritis associated with
      environmental risk factors in Quebec, 1999-2006.
AB  - Childhood nonviral gastroenteritis is a priority for various public health
      authorities. Given that waterborne transmission is sometimes incriminated during
      investigation of gastroenteritis outbreaks, the authors hypothesized that
      watershed characteristics may influence the occurrence of this disease and could
      contribute additional insights for better prevention and control. The study
      described here aimed to investigate watershed characteristics in relation to
      nonviral gastroenteritis and specifically three bacterial and parasitic forms of
      childhood gastroenteritis to assess their relative importance in the province of
      Quebec, Canada. Information on children aged 0-4 years with bacterial or
      parasitic enteric infections reported through ongoing surveillance between 1999
      and 2006 in the province of Quebec was collected. Factors measured at the
      municipal and watershed levels were analyzed using multilevel models with a
      Poisson distribution and log link function. Childhood nonviral gastroenteritis,
      giardiasis, and campylobacteriosis were positively associated with small
      ruminants and cattle density. Childhood salmonellosis was positively associated
      with cattle density. Also, childhood campylobacteriosis incidence was positively
      associated with larger watershed agricultural surface. In addition to local
      agroenvironmental factors, this analysis revealed an important watershed effect.

PMID- 24288850
TI  - The emergency response program at the Agency for Toxic Substances and Disease
      Registry.
AB  - As part of our continuing effort to highlight innovative approaches to improving
      the health and environment of communities, the Journal is pleased to publish a
      bimonthly column from the U.S. Agency for Toxic Substances and Disease Registry
      (ATSDR). The ATSDR, based in Atlanta, Georgia, is a federal public health agency
      of the U.S. Department of Health and Human Services and shares a common office of
      the Director with the National Center for Environmental Health at the Centers for
      Disease Control and Prevention (CDC). ATSDR serves the public by using the best
      science, taking responsive public health actions, and providing trusted health
      information to prevent harmful exposures and diseases related to toxic
      substances. The purpose of this column is to inform readers of ATSDR's activities
      and initiatives to better understand the relationship between exposure to
      hazardous substances in the environment and their impact on human health and how
      to protect public health. We believe that the column will provide a valuable
      resource to our readership by helping to make known the considerable resources
      and expertise that ATSDR has available to assist communities, states, and others
      to assure good environmental health practice for all is served.

PMID- 24288851
TI  - Culture shift: strengthening the role of environmental health in public health
      performance improvement efforts.
AB  - NEHA strives to provide up-to-date and relevant information on environmental
      health and to build partnerships in the profession. In pursuit of these goals, we
      feature a column from the Environmental Health Services Branch (EHSB) of the
      Centers for Disease Control and Prevention (CDC) in every issue of theJournal. In
      this column, EHSB and guest authors from across CDC will highlight a variety of
      concerns, opportunities, challenges, and successes that we all share in
      environmental public health. EHSB's objective is to strengthen the role of state,
      local, tribal, and national environmental health programs and professionals to
      anticipate, identify, and respond to adverse environmental exposures and the
      consequences of these exposures for human health.

PMID- 24288852
TI  - 2013 environmental health legislation.
AB  - The NEHA Government Affairs program has a long and productive association with
      the National Conference of State Legislatures (NCSL). The organizations have
      worked together on any number of legislative and policy areas that directly
      impact the environmental health profession. One of the keys to the successes of
      the NEHA/NCSL collaboration has been the recognition of the fact that often some
      of the most significant legislation and policy initiatives related to
      environmental public health occur in state legislatures. The states have, in a
      very real sense, been the innovators in developing new programs and practices. In
      recognition of this fact, we have asked NCSL to provide occasional overviews of
      state environmental public health legislative activity, covering topics that are
      of the most pressing public concern. Doug Farquhar, program director for NCSI's
      Environmental Health Program, has worked with NCSL since 1990. Mr. Farquhar
      directs development, management, and research for the Environmental Health
      Program. These projects encompass consultation and policy analysis of state and
      federal policies and statutes, regulations, and programs regarding environmental
      and related topics for state legislatures and administrative programs. Amy Ellis
      is a law clerk for NCSL within the Environment, Energy, and Transportation Group.
      As a law clerk she has researched a wide variety of environmental health
      policies. She is expected to obtain her JD from the University of Colorado Law
      School in 2015.

PMID- 24288853
TI  - By 2030 over 50% of colleges will collapse: part 1.

PMID- 24288854
TI  - New perspectives on environmental health: the approval of new definitions.

PMID- 24288855
TI  - Francis effect needs to be a long-term reality.

PMID- 24288856
TI  - Francis sparks rise in nurse posts.

PMID- 24288857
TI  - Friends and family test omits to tell us what needs to be fixed.

PMID- 24288858
TI  - Newly qualified nurses must be supported so we don't lose them.

PMID- 24288859
TI  - Audit of missed or delayed antimicrobial drugs.
AB  - Although the National Patient Safety Agency published a Rapid Response Report on
      reducing harm resulting from omitted or delayed medication in 2010, omitted doses
      continue to occur frequently. The Francis report raised awareness of the problem
      and its potential impact on care. This article discusses the findings from a
      multicentre point-incident collaborative audit, focused on antimicrobials. We
      reviewed records from 6,062 patients prescribed 21,825 doses of antimicrobials;
      13% were affected by omitted doses. Some doses are omitted in patients' best
      interests, but organisations need to identify those that occur for no acceptable
      reason and target them as a priority. We need national initiatives, strong local
      nursing leadership and multidisciplinary engagement to support a range of
      targeted interventions to achieve effective, sustained improvements. The tools
      developed from this study may help others to begin tackling this issue.

PMID- 24288860
TI  - Confidence in leadership among the newly qualified.
AB  - The Francis report highlighted the importance of strong leadership from health
      professionals but it is unclear how prepared those who are newly qualified feel
      to take on a leadership role. We aimed to assess the confidence of newly
      qualified health professionals working in the West Midlands in the different
      competencies of the NHS Leadership Framework. Most respondents felt confident in
      their abilities to demonstrate personal qualities and work with others, but less
      so at managing or improving services or setting direction.

PMID- 24288861
TI  - Managing acute asthma in primary care.
AB  - Asthma is a common inflammatory condition affecting the airways. Many people with
      it fail to achieve a satisfactory level of control and, consequently, have
      recurrent acute exacerbations. These can occur due to allergen exposure, viral
      infections or for no identifiable reason. Guidelines categorise exacerbations
      into three categories, from moderate to life threatening. Prompt assessment and
      treatment using bronchodilators and corticosteroids are essential, as is follow
      up to identify and manage factors that may have contributed to the exacerbation.
      This article discusses guidelines on the management and causes of acute
      exacerbations, and follow-up care that should be provided.

PMID- 24288862
TI  - Use of exhaled nitric oxide in asthma care.
AB  - Nitric oxide in exhaled breath is a biomarker of continuing inflammatory process
      in the airways, and its measurement can be used to predict responsiveness to
      steroid treatment in patients with asthma. This article describes the range of
      uses of exhaled nitric oxide measurements in respiratory care, particularly in
      primary care settings, and reviews evidence on this non-invasive test.

PMID- 24288863
TI  - 60 seconds with Jenny Wright.

PMID- 24288864
TI  - Putting a stop to paralysis.

PMID- 24288865
TI  - Commitment is essential every day.

PMID- 24288866
TI  - Reflections.

PMID- 24288867
TI  - New AHS staffing models cause for concern.

PMID- 24288868
TI  - RN pride takes a hit at renewal.

PMID- 24288869
TI  - Informatics is considered a core competency for safe clinical practice.

PMID- 24288870
TI  - Physician assistants in the workplace.

PMID- 24288871
TI  - Managing overfill during preparation and delivery of intravenous medications.

PMID- 24288872
TI  - The nurse who changed my treatment.

PMID- 24288873
TI  - Volunteer nurse brings new life to old lessons.

PMID- 24288874
TI  - Managing dis rup tive behaviour in the health-care workplace.

PMID- 24288875
TI  - Call to ARMS: recent measles outbreak reminds us of the importance of
      immunizations.
AB  - As health advisories go, the one this past summer released by the Public Health
      Agency of Canada went by largely unnoticed. Issued in July, the advisory alerted
      Canadians to the identification of nearly 30 cases of measles across six
      different provinces-including Alberta. Most of those cases were travel related,
      and involved travelers bringing measles back with them to Canada. A few small
      news articles followed, but by August most people had forgotten all about it.
      Except for experts and epidemiologists, who recognize that outbreaks like these
      should remind everyone that measles is not only poised for a resurgence, but
      already gaining headway in some parts of the world. And that's exactly why RNs
      and NPs should be encouraging more people to take vaccinations seriously.

PMID- 24288876
TI  - Supporting nursing educators to improve retention. Red Deer College introduces
      faculty navigators.

PMID- 24288877
TI  - Closing perspectives: what's in it for you?

PMID- 24288878
TI  - Consenting to pediatric critical care research: understanding the perspective of
      parents.
AB  - Pediatric clinical research is dependent on obtaining consentfrom the parents or
      legal guardian of eligible patients. Little is known about parents' perspectives
      and the process by which they make the decision to enroll their child in a
      pediatric critical care trial. OBJECTIVE: To describe the experience of
      parents/legal guardians who consented or declined consent for their child to be
      enrolled in a pediatric critical care research study. Factors that influenced
      parents' decisions and suggestions for improving and modifying the consent
      process were explored. METHOD: This study used a qualitative descriptive research
      design. Seven semi-structured qualitative interviews were conducted with parents
      who had given or declined consent for their child to participate in a clinical
      research study while their child was in a pediatric critical care unit in one of
      two Canadian pediatric teaching hospitals. Parents were interviewed within 48
      hours of their child's transfer from the PICU to a hospital ward unit. The
      interviews were audio recorded, transcribed, and analyzed using a content
      analysis method. RESULTS: Parental decision-making related to research consent in
      the context of pediatric critical care is influenced by specific characteristics
      of the consent encounter (timing, location, and information), parent (emotional
      state, decision-making style, familiarity with environment, past experience, and
      personal motivation), child (condition and response to pain/needles) and study
      (risk, method, burden, and benefit). Parents identified that the timing and ways
      in which they received information during the consent encounter could be
      improved. CONCLUSION: Pediatric critical care researchers can improve the
      parental consent encounter experience by considering how parents perceive the
      approach to consent for a research trial for their child to balance the need to
      support parents with the need for participants in pediatric critical care
      research trials.

PMID- 24288879
TI  - The evolution of the dental practice.

PMID- 24288880
TI  - Congratulations on the March/April PDJ.

PMID- 24288881
TI  - Odontomas: A review of diagnosis, classification, and challenges.

PMID- 24288882
TI  - [Masculine and feminine].

PMID- 24288883
TI  - [We must fight against stereotypes from a young age in order to give our children
      the greatest career choices possible].

PMID- 24288884
TI  - [The question of gender in nursing].
AB  - The question of gender in the nursing profession. The proportion of men in
      nursing has varied over the centuries. However, nursing training was only opened
      up to men after the Second World War. This article reflects on the influence of
      gender and the place of men in nursing care from yesterday to today.

PMID- 24288885
TI  - [Grouping of nurses: gender diversity or the neutralization of gender?].
AB  - Professional nurses' group: towards gender diversity or the neutralisation of
      gender? The nursing profession is essentially feminine. It is interesting to
      listen to what professionals, and particularly women, have to say about the
      question. Different opinions emerge and conclusions are established. The first
      step is awareness.

PMID- 24288886
TI  - [Male and female nurses, do they differ in care?].
AB  - Male and female nurses, how does the care they provide differ? While male and
      female nurses recognise the influence of their gender on their professional
      practices, these differences correspond to existing cultural representations.
      They can be lessened through experience and practices become enriched with new
      ways of providing care. Is care more a female domain? Do the men who join this
      profession have different ways of providing care than women? This article offers
      an ethnological approach through a research master's thesis.

PMID- 24288887
TI  - [Men in nursing].
AB  - Men in nursing. Gender diversity in teams is usually welcomed both by women and
      men. However, it is not always synonymous with synergy and male nurses would like
      to rid themselves of certain stereotypes. Four male nurses share their experience
      of working within predominantly female teams.

PMID- 24288888
TI  - [Private practice, a sector that attracts male nurses].
AB  - Private practice, a sector which attracts male nurses. Although the proportion of
      women and men within the nursing profession remains stable, the representation of
      male nurses in private practice has been increasing steadily since 2002 which
      raises certain questions. This article attempts to explain this phenomenon.

PMID- 24288889
TI  - [Nurse anesthetist for the French emergency medical services].
AB  - Nurse anaesthetist for the French emergency medical services. Emmanuel Dinot is a
      nurse anaesthetist for the emergency medical services in Yvelines, France.
      Fascinated by the management of emergency situations in non-hospital settings, he
      paints the portrait of a nursing context where teamwork, rigour, technical
      expertise and flexibility in spite of stress increase the efficiency of care.

PMID- 24288890
TI  - [Cooperation protocols, terms and repercussions].
AB  - Cooperation protocols, terms and repercussions. When regulating the health
      sector, legislators are faced with the persistent problem of managing a
      structural shortage of people and means while they are unable to offer new
      resources. One solution is to allow professionals to carry out procedures which,
      under the regulations, are the responsibility of others. A look at the
      repercussions of cooperation protocols for healthcare professionals.

PMID- 24288891
TI  - [What patients think of patient education].
AB  - What patients think of therapeutic education. Therapeutic education for patients
      has proven beneficial in the management of many chronic diseases. At the Marie
      Madeleine hospital centre in Forbach, France, where a therapeutic education unit
      has been in place since 2006, a satisfaction survey undertaken in a group of
      patients with heart failure shows areas for improvement.

PMID- 24288892
TI  - [Palliative care of bowel obstruction with peritoneal cancer].
AB  - Palliative care of bowel obstruction with peritoneal carcinosis. Bowel
      obstruction is a frequent cancer complication. It can be treated at home,
      particularly by private and registered nurses. Various medicated treatments seek
      to relieve the symptoms, which include pain, vomiting and hypersecretion.

PMID- 24288893
TI  - [A hospital stay without bedsores].
AB  - A hospital stay without bedsores. The skin of elderly people is thin and fragile.
      After extended bed-rest, the skin's resources are rapidly depleted. The risk of
      bedsores becomes imminent. But a high-quality multi-disciplinary partnership can
      prevent bedsores in elderly patients with multiple illnesses. Example around a
      clinical case.

PMID- 24288895
TI  - A new hospital building project.

PMID- 24288894
TI  - [Music as mediation in a home for adolescents].
AB  - Music as mediation in a home for adolescents. At the H6pital Cochin
      homeforadolescents in Paris, therapeutic workshops give young hospital patients
      the opportunity to express themselves outside of the daily care environment. Just
      like the cultural workshops, the music workshop enhances the well-being of these
      adolescents in difficulty. Experience sharing.

PMID- 24288896
TI  - [Nursing care of blunt abdominal and pelvic trauma].

PMID- 24288898
TI  - [Training for nursing assessment].

PMID- 24288897
TI  - [Fighting malnutrition with better communication].

PMID- 24288899
TI  - [Peripherally inserted central catheterization].

PMID- 24288900
TI  - [Iron deficiency anemia without a source of bleeding. A diagnostic mosaic].

PMID- 24288901
TI  - [For every patient a good word: with the rural physician on house calls].

PMID- 24288902
TI  - [Patient escape].

PMID- 24288903
TI  - [Physician's skepticism at a marathon run].

PMID- 24288904
TI  - [Migrants and extended stay vacationers. How do I manage prescription requests
      above quarterly needs].

PMID- 24288905
TI  - [Geriatric basic assessment. Must we repeat this for EBM 2013?].

PMID- 24288906
TI  - [Impending crisis in ambulatory care. Against the errors of the corporate
      system].

PMID- 24288907
TI  - [Infection emergency: life threatening danger of Pneumococcus and co].

PMID- 24288908
TI  - [Pneumococcal vaccines for adults: which age groups should be vaccinated - and
      with what?].

PMID- 24288909
TI  - [Naturopathy consultation. Venous insufficiency].

PMID- 24288910
TI  - [Your patient needs antithrombotic drugs, 8. Which thrombosis prevention for
      tumor patients?].

PMID- 24288911
TI  - [Tormenting skin condition urticaria: what is causing the hives?].

PMID- 24288912
TI  - [Post-traumatic stress disorder in every 5th patient. Psychological trauma on the
      intensive care unit].

PMID- 24288913
TI  - [Nobel Prize for cell biologists. An intricate sophisticated system against chaos
      inside the cell].

PMID- 24288914
TI  - [Nocturnal leg calf cramps. What are the therapy options?].

PMID- 24288915
TI  - [Conjunctival hemorrhage. Acute manifestation benign, long-term alarming].

PMID- 24288916
TI  - [Restrictive transfusion strategy in upper gastrointestinal hemorrhage].

PMID- 24288917
TI  - [Selenium supplement does not protect against heart diseases].

PMID- 24288918
TI  - [With a dog heart disease patients live longer].

PMID- 24288919
TI  - [In acute exacerbated COPD steroids last over 5 days].

PMID- 24288920
TI  - [Emergency physician interventions in a gambling casino declined since the
      smoking ban].

PMID- 24288921
TI  - [High protein intake or many carbohydrates for weight loss?].

PMID- 24288922
TI  - [Hypersexual disorder].

PMID- 24288923
TI  - [Leishmaniasis].

PMID- 24288924
TI  - [Interventional cardiology - what's hot and new?].

PMID- 24288925
TI  - [Manual medicine applied at the cervical spine: do we have to be afraid of
      vertebral artery dissection?].

PMID- 24288926
TI  - [Migraine in adolescence].

PMID- 24288927
TI  - [Diabetic foot: how to avoid therapeutic mistakes].

PMID- 24288928
TI  - [Controlling sore throat pain and inflammation are the most important therapy
      goals].

PMID- 24288929
TI  - [Angina pectoris. Ranolazine is effective in myocardial ischemia therapy].

PMID- 24288930
TI  - [St.John's wort extract prescribed with foresight].

PMID- 24288931
TI  - Special investigation: overseas recruitment Trusts forced seek staff road.

PMID- 24288932
TI  - All nurses need to know how to give health improvement advice.

PMID- 24288933
TI  - Accepting a real-term pay cut is accepting an assault on nursing.

PMID- 24288934
TI  - Display staffing levels to show importance placed on safe care.

PMID- 24288935
TI  - Innovation:CBT-based support groups for postnatal depression.
AB  - Postnatal depression can have serious implications for mother/child bonding and
      damage relationships between parents. Approaches to treat it need to overcome
      barriers that have led to high attrition in some group or clinic-based postnatal
      depression treatment studies. This retrospective evaluation explored the benefits
      of offering postnatally depressed mothers group support based on cognitive
      behavioural therapy. It helped to improve women's self-esteem and self-worth and
      to make them feel safe and supported.

PMID- 24288936
TI  - Varicose veins: diagnosis and management.
AB  - Varicose veins affect up to one-third of the UK population. Many health
      professionals are therefore likely to come into contact with patients who have
      venous disease and need to understand how to assess, manage and treat this
      condition. This article discusses the updated guidelines from the National
      Institute for Health and Care Excellence on how health professionals can best
      treat patients who present with varicose veins.

PMID- 24288937
TI  - Effects of complementary therapies in cancer care.
AB  - Evaluating practice is central to any NHS service. Evidence-based approaches are
      essential to ensure that services are run effectively, develop according to need
      and continue to be commissioned. A complementary therapies service was introduced
      at Whipps Cross University Hospital for patients with cancer and palliative care
      needs. The service was evaluated using an evaluation tool. Findings from the
      evaluation covered symptom management, wellbeing and therapeutic modalities. It
      is important to undertake individualised qualitative Complemenevaluations as well
      as quantitative studies.

PMID- 24288939
TI  - 60 seconds with Martin Steggall.

PMID- 24288938
TI  - Motivational interviewing and HIV drug adherence.
AB  - Despite advances in HIV treatment, adherence rates remain low, with only around
      50-70% of those who should be taking antiretroviral therapy fully concordant with
      the treatment regimen. This article explores why this might be. It analyses the
      literature on motivational interviewing, and its effectiveness in improving
      patient adherence to antiretroviral therapy in the treatment of HIV.

PMID- 24288940
TI  - Nurses without borders.

PMID- 24288941
TI  - Using mindfulness to secure a job.

PMID- 24288942
TI  - Enteric pathogens and reactive arthritis: a systematic review of Campylobacter,
      salmonella and Shigella-associated reactive arthritis.
AB  - Reactive arthritis (ReA) is a spondyloarthropathic disorder characterized by
      inflammation of the joints and tissues occurring after gastrointestinal or
      genitourinary infections. Diagnostic criteria for ReA do not exist and,
      therefore, it is subject to clinical opinion resulting in cases with a wide range
      of symptoms and definitions. Using standardized diagnostic criteria, we conducted
      a systematic literature review to establish the global incidence of ReA for each
      of the three most commonly-associated enteric pathogens: Campylobacter,
      Salmonella, and Shigella. The weighted mean incidence of reactive arthritis was
      9, 12, and 12 cases per 1,000 cases of Campylobacter, Salmonella and Shigella
      infections respectively. To our knowledge, this is the first systematic review of
      worldwide data that use well-defined criteria to characterize diarrhoea
      associated ReA. This information will aid in determining the burden of disease
      and act as a planning tool for public-health programmes.

PMID- 24288943
TI  - Pulmonary tuberculosis in severely-malnourished or HIV-infected children with
      pneumonia: a review.
AB  - Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely
      malnourished and HIV-positive children has received very little attention,
      although this is very important in the management of pneumonia in children living
      in communities where TB is highly endemic. Our aim was to identify confirmed TB
      in children with acute pneumonia and HIV infection and/or severe acute
      malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the
      WHO median, or presence of nutritional oedema). We conducted a literature search,
      using PubMed and Web of Science in April 2013 for the period from January 1974
      through April 2013. We included only those studies that reported confirmed TB
      identified by acid fast bacilli (AFB) through smear microscopy, or by culture
      positive specimens from children with acute pneumonia and SAM and/or HIV
      infection. The specimens were collected either from induced sputum (IS), or
      gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung
      aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or
      patchy consolidation and/or clinical evidence of severe/ very severe pneumonia
      according to the WHO criteria of acute respiratory infection. A total of 17
      studies met our search criteria but 6 were relevant for our review. Eleven
      studies were excluded as those did not assess the HIV status of the children or
      specify the nutritional status of the children with acute pneumonia and TB. We
      identified only 747 under-five children from the six relevant studies that
      determined a tubercular aetiology of acute pneumonia in children with SAM and/or
      positive HIV status. Three studies were reported from South Africa and one each
      from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were
      enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified
      with active TB respectively, with a total of 93 (12%) children with active TB.
      Among 610 HIV-infected children in three studies from South Africa and 137 SAM
      children from other studies, 64 (10%) and 29 (21%) isolates of M. tuberculosis
      were identified respectively. Children from South Africa were infected with HIV
      without specification of their nutritional status whereas children from other
      countries had SAM but without indication of their HIV status. Our review of the
      existing data suggests that pulmonary tuberculosis may be more common than it is
      generally suspected in children with acute pneumonia and SAM, or HIV infection.
      Because of the scarcity of data, there is an urgent need to investigate PTB as
      one of the potential aetiologies of acute pneumonia in these children in a
      carefully-conducted larger study, especially outside Africa.

PMID- 24288944
TI  - Distribution of vibrio species in shellfish and water samples collected from the
      atlantic coastline of south-east Nigeria.
AB  - Crayfish, lobster, and sea-water samples collected from five fishing islands on
      the Atlantic coast-Bight of Biafra (Bonny)-belonging to Ibaka Local Government
      Area of Akwa-Ibom State of Nigeria were bacteriologically evaluated on
      thiosulphate citrate bile-salt sucrose (TCBS) agar for Vibrio load and
      pathotypes. Mean log10 Vibrio counts of 7.64+/-2.78 cfu/g (in crayfish), 5.07+/
      3.21 cfu/g (in lobster), and 3.06+/-2.27 cfu/mL (in sea-water) were obtained in
      rainy season (June-July) while counts in the dry season (November-December) were
      6.25+/-1.93 cfu/g, 5.99+/-1.54 cfu/g, and 3.84+/-1.78 cfu/mL respectively. The
      physicochemical measurements (temperature, pH, and total dissolved solutes) of
      the sea-water did not vary significantly in the two seasons across all five
      islands. Vibrio species isolated were Vibrio cholerae (both O1 and non-O1
      serotypes), V parahaemolyticus, V vulnificus, V mimicus, and V fluvialis. Both
      Ogawa and Inaba subtypes of V cholerae O1 serotype were found. In addition, the
      Hikojima subtype, which had not been previously reported in the region, was
      isolated in two samples. The results show that these Vibrio species are endemic
      in the area.

PMID- 24288945
TI  - Caretakers' perception towards using zinc to treat childhood diarrhoea in rural
      western Kenya.
AB  - Zinc treatment for diarrhoea can shorten the course and prevent future episodes
      among children worldwide. However, knowledge and acceptability of zinc among
      African mothers is unknown. We identified children aged 3 to 59 months, who had
      diarrhoea within the last three months and participated in a home-based zinc
      treatment study in rural Kenya. Caretakers of these children were enrolled in two
      groups; zinc-users and non-users. A structured questionnaire was administered to
      all caretakers, inquiring about knowledge and appropriate use of zinc. Questions
      on how much the caretakers were willing to pay for zinc were asked. Proportions
      were compared using Mantel-Haenszel test, and medians were compared using
      Wilcoxon Rank Sum test. Among 109 enrolled caretakers, 73 (67%) used zinc, and 36
      (33%) did not. Sixty-four (88%) caretakers in zinc-user group reported
      satisfaction with zinc treatment. Caretakers in the zinc-user group more often
      correctly identified appropriate zinc treatment (98%-100%) than did those in the
      non-user group (64-72%, p<0.001). Caretakers in the zinc-user group answered more
      questions about zinc correctly or favourably (median 10 of 11) compared to those
      in the non-user group (median 6.3 of 11, p<0.001). Caretakers in the zinc-user
      group were willing to pay more for a course of zinc in the future than those in
      the non-user group (median US$ 0.26, p<0.001). Caretakers of children given zinc
      recently had favourable impressions on the therapy and were willing to pay for it
      in the future. Active promotion of zinc treatment in clinics and communities in
      Africa could lead to greater knowledge, acceptance, and demand for zinc.

PMID- 24288946
TI  - Eating habits and body-weights of students of the university of belgrade, serbia:
      a cross-sectional study.
AB  - The purpose of this survey was to quantify the prevalence of overweight and
      obesity among a sample of students in Belgrade University, Serbia and to describe
      their main eating habits. A total of 1,624 questionnaire responses were analyzed
      (response rate 97.3%). The students were recruited during mandatory annual check
      ups in April-June 2009. All subjects completed the questionnaire; height (in cm)
      and weight (in km) were measured by two physicians. Results were assessed
      statistically. Almost every fourth male student was overweight. Strikingly, 15%
      of female students were underweight. Highly-significant difference was found
      between average body mass index (BMI) of male and female students (F=317.8,
      p=0.001). Students' BMI did not correlate with average family income or with the
      frequency of taking breakfast (p=-0.064, p=0.152 for males and p=0.034, p=0.282
      for females respectively). There is a growing demand for global health strategies
      which would encourage healthy body-image and figure; thus, these initiatives
      should mobilize the society on a national and international level.

PMID- 24288947
TI  - TV viewing, independent of physical activity and obesogenic foods, increases
      overweight and obesity in adolescents.
AB  - The aim of this study was to estimate the prevalence of overweight and obesity
      (OAO) and associated risk factors in a representative sample of students aged 11
      20 years in Urmia, Iran. In this population-based cross-sectional study, a
      multistage random cluster-sampling method was used, through which 2,498 students
      were selected. OAO were defined based on criteria set by the US Center for Health
      Statistics in collaboration with the US Center for Chronic Disease Prevention and
      Health Promotion under the Centers for Disease Control and Prevention (CDC). OAO
      risk factors were assessed using a questionnaire containing questions about TV
      viewing, nutrition, physical activities (PA), social and economic factors.
      Contents of the questionnaire were validated by calculating the content validity
      ratio (CVR) and content validity index (CVI), based on the responses elicited
      from 15 experts. Reliability of the questionnaire was obtained from a test and re
      test of the questionnaire completed by 15 students. To analyze the data, x2-test,
      t-test, and multiple logistic regression analysis were conducted. The prevalence
      of OAO was found to be 14.1% among the 11-20 years old students of junior and
      senior high schools. The results of multiple logistic regression analysis
      indicated that the educational level of mothers, type of school, and the time
      spent on viewing TV were associated with an increased risk of OAO while
      obesogenic foods and PA had no effect on the frequency of OAO [Odds ratio (OR)
      for the time spent on watching TV one hour more than usual equals 1.27 at
      p=0.001]. The direct correlation between TV viewing and OAO, which is independent
      of PA and obesogenic foods, needs to be carefully investigated through randomized
      clinical trials and cohort studies.

PMID- 24288949
TI  - Malnutrition among 3 to 5 years old children in Baghdad city, Iraq: a cross
      sectional study.
AB  - The unstable geopolitical situation in Iraq since 2003 still affects the health
      of people, especially children. Several factors may indirectly affect a child's
      nutritional status. The main aim of this study was to identify factors
      contributing to malnutrition among 3 to 5 years old children in Baghdad city,
      Iraq. Two hundred twenty children aged 3 to 5 years were chosen randomly from
      four kindergartens in Baghdad city according to the cross-sectional design. The
      nutritional status of the children was assessed using a weight-for-age z-score
      based on the World Health Organization 2007 cutoff points, in which any child
      with a z-score of <-2 is considered to be malnourished. The overall prevalence
      rate of underweight children was 18.2%. There was no significant difference in
      the prevalence rate between males and females (p=0.797). However, the percentage
      of underweight children was slightly higher among females (18.9%) compared to
      males (17.6%). There was no association between parents' educational level or
      employment status and childhood malnutrition. There was no association between a
      family's movement from their house and childhood malnutrition (p=0.322). Living
      in an unsafe neighbourhood and having a family member killed during the past five
      years were significantly associated with childhood malnutrition (p=0.016 and
      0.018 respectively). Childhood malnutrition is still a public-health concern in
      Baghdad city, especially after the war of 2003. Malnutrition is significantly
      associated with living in unsafe neighbourhoods and at least one family member
      having been killed during the past five years.

PMID- 24288948
TI  - Protective effect of fish oil supplementation on DNA damage induced by cigarette
      smoking.
AB  - The study examined the influence of fish oil (FO) supplementation on serum 8
      hydroxy-2'-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and
      total antioxidant capacity (TAC) among male cigarette smokers. This double-blind,
      placebo-controlled randomized study was conducted among healthy cigarette smokers
      (n=40) who were part of a larger prospective cohort study. Twenty smokers were
      randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers
      received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood
      samples before and after the intervention. Serum 8-OHdG significantly decreased
      (p=0.001) and TAC increased (p<0.001) after 3 months of treatment with FO.
      Between baseline and endline, the difference in 8-OHdG significantly correlated
      with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The
      study provides evidence that FO supplementation can modify decreased antioxidants
      and increased oxidative DNA damage in cigarette smokers.

PMID- 24288950
TI  - Food insecurity and its sociodemographic correlates among Afghan immigrants in
      Iran.
AB  - The study determined the prevalence of food insecurity and its sociodemographic
      determinants among Afghan immigrants in two major cities of Iran. This cross
      sectional study was conducted on a sample of 310 adult females from immigrant
      Afghan households in Tehran (n=155) and Mashhad (n=155), who were recruited
      through multistage sampling. Data were collected through face-to-face interviews,
      using a questionnaire. Food security was measured by a locally-adapted Household
      Food Insecurity Access Scale. More than 60% suffered from moderate-to-severe food
      insecurity, 37% were mildly food-insecure while about 23% were food-secure. Food
      insecurity was significantly more prevalent in female-headed households,
      households whose head and spouse had lower level of education, belonged to the
      Sunni sect, and those with illegal residential status, unemployment/low job
      status, not owning their house, low socioeconomic status (SES), and living in
      Mashhad. Prevalence of food insecurity was relatively high among Afghan
      immigrants in Iran. This calls for the need to develop community food security
      strategies for ensuring their short- and long-term health.

PMID- 24288951
TI  - Screening utility, local perceptions, and care-seeking for reported jaundeesh
      among respondents lacking signs of icterus in rural Bangladesh.
AB  - In rural Bangladesh, acute viral hepatitis presents a significant burden on the
      public-health system. As part of the formative work for a large epidemiologic
      study of hepatitis E in rural Bangladesh, we sought to identify local terms that
      could be used for population-based screening of acute viral hepatitis.
      Exploration of the local term jaundeesh for screening utility identified a high
      burden of reported jaundeesh among individuals without symptoms of icterus.
      Recognizing that local perceptions of illness may differ from biomedical
      definitions of disease, we also sought to characterize the perceived aetiology,
      care-seeking patterns, diagnostic symptoms, and treatments for reported jaundeesh
      in the absence of icteric symptoms to inform future population-based studies on
      reported morbidities. We conducted a cross-sectional survey among 1,441 randomly
      selected subjects to identify the prevalence of reported jaundeesh and to test
      the validity of this local term to detect signs of icterus. To characterize the
      perceived aetiology and care-seeking patterns for jaundeesh among the majority of
      respondents, we conducted in-depth interviews with 100 respondents who self
      reported jaundeesh but lacked clinical signs of icterus. To describe diagnostic
      symptoms and treatments, in-depth interviews were also performed with 25 kabirajs
      or traditional faith healers commonly visited for jaundeesh. Of the 1,441
      randomly-selected participants, one-fourth (n=361) reported jaundeesh, with only
      a third (n=122) reporting yellow eyes or skin, representative of icterus;
      Jaundeesh had a positive predictive value of 34% for detection of yellow eyes or
      skin. Anicteric patients with reported jaundeesh perceived their illnesses to
      result from humoral imbalances, most commonly treated by amulets, ritual
      handwashing, and bathing with herbal medicines. Jaundeesh patients primarily
      sought folk and spiritual remedies from informal care providers, with only 19%
      visiting allopathic care providers. Although the local term jaundeesh appeared to
      have limited epidemiologic utility to screen for acute symptomatic viral
      hepatitis, this term described a syndrome perceived to occur frequently in this
      population. Future population-based studies conducting surveillance for acute
      hepatitis should use caution in the use and interpretation of self-reported
      jaundeesh. Further study of jaundeesh may provide insight into the appropriate
      public-health response to this syndrome.

PMID- 24288952
TI  - Abortion clients of a public-sector clinic and a non-governmental organization
      clinic in Nepal.
AB  - This paper investigates similarities and differences between abortion clients of
      a public-sector clinic and a non-governmental organization (NGO) clinic in Nepal.
      In 2010, a survey of 1,172 women was conducted in two highly-attended abortion
      clinics in Kathmandu-one public-sector clinic and another operated by an NGO.
      Data on the sociodemographic characteristics of clients, their fertility
      preferences, and use of contraceptives were analyzed. Similarities and
      differences between the two groups of clients were examined by either chi-square
      or t-test. The clients of the two clinics were similar with respect to age
      (27.3+/-5.7 years), education (26.5% had no education), and number of living
      children (1.88+/-1.08). They differed with regard to contraceptive practice, the
      circumstances resulting in unintended pregnancy, and future fertility
      preferences. Just over 50% clients of the public and 35% clients of the NGO
      clinic reported use of contraceptives surrounding the time of unintended
      pregnancy. The groups also differed in the contraceptive methods used and in
      reasons for not using any method. The NGO clinic contributed principally to
      expanding the availability of and access to abortion services.

PMID- 24288953
TI  - Body mass index, waist-circumference and cardiovascular disease risk factors in
      Iranian adults: Isfahan healthy heart program.
AB  - Considering the main effect of obesity on chronic non-communicable diseases, this
      study was performed to assess the association between body mass index (BMI),
      waist-circumference (WC), cardio-metabolic risk factors and to corroborate
      whether either or both BMI and WC are independently associated with the risk
      factors in a sample of Iranian adults. This cross-sectional study was performed
      on data from baseline survey of Isfahan Healthy Heart Program (IHHP). The study
      was done on 12,514 randomly-selected adults in Isfahan, Najafabad and Arak
      counties in 2000-2001. Ages of the subjects were recorded. Fasting blood glucose
      (FBG), 2-hour post-load glucose (2hpp), serum lipids, systolic and diastolic
      blood pressure (SBP and DBP), BMI, WC, smoking status, and total daily physical
      activity were determined. Increase in BMI and WC had a significant positive
      relation with the mean of FBG, 2hpp, SBP, DBP, serum lipids, except for HDL-C
      (p<0.001 for all). After adjustment for age, smoking, physical activity,
      socioeconomic status (SES), and BMI, the highest odds ratio (OR) (95% CI) for
      diabetes mellitus (DM) according to WC was 3.13 (1.93-5.08) and 1.99 (1.15-3.44)
      in women and men respectively. Moreover, the highest ORs based on BMI with
      adjustment for age, smoking, physical activity, SES, and WC were for
      dyslipidaemia (DLP) [1.97 (1.58-2.45) in women and 2.96 (2.41-3.63) in men]. The
      use of BMI or WC alone in the models caused to enhance all ORs. When both BMI and
      WC were entered in the model, the ORs for all risk factors, in men, according to
      BMI, were more compared to WC. However, in women, ORs for DM and hypertension
      (HTN) in WC quartiles were more than in BMI quartiles. BMI is the better
      predictor of DM, HTN, and DLP in men compared to WC. Conversely, in women, WC is
      a superior predictor than BMI, particularly for DM and HTN. Furthermore, the
      measurement of both WC and BMI in Iranian adults may be a better predictor of
      traditional risk factors of CVDs compared to BMI or WC alone.

PMID- 24288954
TI  - Association between maternal anaemia and postpartum depression in an urban sample
      of pregnant women in Iran.
AB  - The aim of this prospective study was to determine the relationship between
      anaemia during pregnancy and postpartum depression. Two hundred eighty-one non
      anaemic mothers with singleton and low-risk pregnancy and no history of
      antidepressant-use were studied. Demographic and reproductive data at week 20
      were obtained. Mothers were followed up and haemoglobin (Hb) was checked at
      delivery. Iranian version of Edinburgh Postpartum Depression Scale (EPDS) was
      completed 4-6 weeks after delivery. Mean age of the mothers was 26.6+/-4 years.
      The prevalence of postpartum depression according to EPDS was 5.5%. Binary
      logistic regression analysis showed that Hb <11 g/dL at delivery would increase
      the chance of postpartum depression (OR 4.64; 95% CI 1.33-16.08). The results
      show that diagnosis and treatment of physiologic factors, especially anaemia,
      would reduce the risk of postpartum depression.

PMID- 24288955
TI  - Fever of unknown origin attributable to haematocolpos infected with Salmonella
      enterica Serotypetyphi resistant to nalidixic acid: a case report.
AB  - The prevalence of nalidixic acid-resistant Salmonella Typhi (NARST) infection is
      increasing worldwide. We are reporting an unusual case of infected haematocolpos
      presenting as urinary obstruction in a patient with fever of unknown origin
      (FUO). This case report highlights the importance of quinolone-resistant typhoid
      fever in the differential diagnosis of any acute febrile illness in countries,
      like India, where Salmonella infection is endemic.

PMID- 24288956
TI  - Characterization of extended-spectrum beta-lactamase-producing clinical isolates
      of Shigella flexneri.

PMID- 24288957
TI  - Highly-resistant E. coli as a common cause of paediatric diarrhoea in India.

PMID- 24288958
TI  - [Proposal of remission criteria for IgA nephropathy].

PMID- 24288959
TI  - [Preface : for the special issue of "kidney and lipid"].

PMID- 24288960
TI  - [WCN2013 satellite symposium "kidney and lipids" Report of the WCN2013 satellite
      symposium"kidney and lipids"].

PMID- 24288961
TI  - [Epidemiology of dyslipidemia in CKD].

PMID- 24288962
TI  - [Clinical practice guidelines for the management of dyslipidemia in chronic
      kidney disease].

PMID- 24288963
TI  - [Abnormal lipoprotein metabolism in CKD].

PMID- 24288964
TI  - [Impact of dyslipidemia on the onset and progression of diabetic complications].

PMID- 24288965
TI  - [Clinical significance of treatment for dyslipidemia in CKD].

PMID- 24288966
TI  - [Effect of statins on renal function].

PMID- 24288967
TI  - [Nephrotic syndrome and LDL apheresis].

PMID- 24288968
TI  - [New evolution in lipoprotein glomerulopathy].

PMID- 24288969
TI  - [Nutrient intake and dietary habit in pediatric, adolescent, and young adult
      kidney transplant recipients].
AB  - AIM: Dietary advice by dietitians based on various factors of nutrient intake and
      dietary habit is important for preventing postoperative complications in adult
      kidney transplant recipients, but little is known about whether such advice is
      also important for pediatric, adolescent, and young adult kidney transplant
      recipients. The purpose of this study was to examine the nutrient intake profiles
      and dietary habits of these recipients and to ascertain the need for dietary
      advice by dietitians. SUBJECTS AND METHODS: This study involved 22 kidney
      transplant recipients with an estimated glomerular filtration rate> or =60
      mL/min/1.73 m2 with no dietary restrictions. Nutrient intake was measured using a
      food frequency questionnaire based on food groups and evaluated using the
      reference values given in the Dietary Reference Intakes for Japanese (DRIs-J)for
      2010 and the daily average intake of the National Health and Nutrition Survey
      Japan, 2010. RESULTS: The mean age of the patients at the time of enrollment was
      17.6+/-4.4 years(8.7 28.5 years). Energy and carbohydrate intakes were below the
      DRIs-J reference value in 18 patients(81.8 %), and the ratio of total fat to
      total energy was above the DRIs-J reference value in 20 patients(90.9 %). Vitamin
      B, vitamin B6, magnesium, and zinc intakes were below the DRIs-J reference value
      in all patients (100 %). Food group intakes that were less than 75 % of the
      values reported in the National Health and Nutrition Survey Japan were pulses and
      algae in 18 patients(81.8 %), green and yellow vegetables in 14 patients(63.6 %),
      other vegetables in 19 patients(86.4 %), and nuts and seeds in 16 patients(72.7
      %). CONCLUSION: This study suggests that dietary advice by dietitians is
      necessary for pediatric, adolescent, and young adult kidney transplant recipients
      to improve their nutrient intake and dietary habits.

PMID- 24288970
TI  - [Complete remission of repeated recurrent membranous nephropathy after non
      myeloablative allogeneic peripheral blood stem cell transplantation].
AB  - A 64-year-old man with treatment-related myelodysplastic syndrome (MDS) underwent
      non-myeloablative allogeneic peripheral blood stem cell transplantation from a
      fully HLA-matched sibling. Seven months after transplantation, he suffered from
      nephrotic syndrome (proteinuria 16.67 g/day) around two weeks atter tapering
      tacrolimus (TAC) for the prophylaxis of graft-versus-host disease(GVHD). A renal
      biopsy revealed membranous nephropathy (Stage I ). Treatment with prednisolone
      (PSL), starting with 50 mg daily, resulted in incomplete remission type I.
      Although remission was maintained for 7 months, nephrotic syndrome recurred
      (proteinuria 7.81 g/day)after tapering PSL(5 mg/day) (18 months after
      transplantation). His PSL dose was increased again to 50 mg daily, and
      proteinuria improved again. Two weeks after discontinuation of TAC as it was
      suspected of worsening his renal function, proteinuria increased again to 6.37
      g/day (21.5 months after transplantation). After administration of cyclosporin A
      (CsA) (30 mg/day) instead of TAC, proteinuria re-improved and complete remission
      of nephrotic syndrome was achieved. In this case, nephrotic syndrome worsened
      twice just after tapering or discontinuing immunosuppressive medication, and
      reinforcement of immunosuppression was effective in improving proteinuria. As
      hematopoietic cell transplantation (HCT) is an increasingly common treatment
      worldwide, the opportunities to see patients with nephrotic syndrome after HCT
      are also increasing. Our case serves as a reference to manage the recurrence of
      nephrotic syndrome after HCT.

PMID- 24288971
TI  - [Case of serious HIV-associated nephropathy resulting in the introduction of
      hemodialysis].
AB  - A previously healthy 46-year-old black man visited the other hospital because of
      fever, appetite loss and nausea. Renal dysfunction, liver injury, and a highly
      markedly elevated LDH level were found. Abdominal CT demonstrated enlarged liver,
      spleen, kidney and lymph nodes. Human immunodeficiency virus (HIV) was
      serologically positive. His serum BUN, creatinine and potassium were 74.9 mg/dL,
      11.78 mg/dL, and 5.6 mEq/L, respectively. After admission, anuria persisted and
      the progression of renal failure continued despite various treatment methods,
      necessitating the introduction of maintenance hemodialysis(HD). A kidney biopsy
      was performed to confirm classical HIV-associated nephropathy (HIVAN).
      Antiretroviral therapy (ART) was started. Although urine was transiently
      excreted, HD could not be discontinued. It has been reported that HIVAN is too
      difficult to treat and that kidney dysfunction seldom recovers. HIVAN is well
      known to occur frequently in black HIV-infected patients. However, in Japan,
      there have been only a few reports describing patients with serious HIVAN and
      renal failure necessitating HD. We present here a very rare case with HIVAN, with
      reference to some recent findings.

PMID- 24288972
TI  - [Case of pseudohypercreatininemia associated with monoclonal IgM gammopathy].
AB  - An 80-year-old man with well controlled hypertension for eight years and
      monoclonal IgM gammopathy was referred to our hospital in May 2010 due to
      persistent elevation of serum creatinine(s-Cr). At our hospital, urine and blood
      tests showed no abnormal findings as BUN and Cr were 15.0 mg/dL and 0.91 mg/dL,
      respectively. In contrast the referring hospital had obtained values of 10.4
      mg/dL and 4.8 mg/dL, respectively. This discrepancy was replicated when s-Cr was
      measured in another sample from this patient using the enzyme assay kits employed
      by the referring hospital and our hospital. High-performance liquid
      chromatography (HPLC), which is the standard method for measuring s-Cr, gave a
      value in the normal range. After removing high molecular weight proteins (>3,000
      D)from the serum sample, the s-Cr levels measured with the respective kits were
      similar. Since elevation of s-Cr was linked to that of IgM at the referring
      hospital, we diagnosed the patient as having pseudohypercreatininemia with
      monoclonal IgM gammopathy.

PMID- 24288973
TI  - [PUF passive air sampling of polycyclic aromatic hydrocarbons in atmosphere of
      the Yangtze River Delta, China: spatio-temporal distribution and potential
      sources].
AB  - Atmosphere is regarded to be an important media in the environmental pollution
      research area. Passive air sampling was one of the effective complementary
      sampling techniques for the active high volume air sampler in recent decades. A
      regional scale investigation on the atmospheric polycyclic aromatic hydrocarbons
      (PAHs) was conducted in the Yangtze River Delta (YRD). Polyurethane foam based
      passive air samplers were used to collect the atmospheric PAHs from 31 sampling
      sites in this area. PAHs concentrations ranged from 10.1 ng x m(-1) to 367 ng x
      m(-3) in this study. The annual average concentration of benzo [a] pyrene (BaP)
      reached 2.25 ng x m(-3), which was two times higher exceeding the national
      standard, GB 3095-2012. The atmospheric PAHs during four seasons decreased in the
      following order: autumn > winter > spring > summer. Larger BaP excessive areas
      were found in autumn and winter than other seasons. Moreover, an obvious emission
      of BaP was confirmed during the winter time. Traffic related petroleum
      combustion, coal and biomass burning, and coke oven were identified as potential
      sources of atmospheric PAHs, contributing 38.1%, 42.4%, and 19.5%, respectively.

PMID- 24288974
TI  - [Quantitative analysis of nitrate in atmospheric particulates PM2.5 with Fourier
      transform infrared spectroscopy].
AB  - Airborne fine particulate matter PM2.5 as one of composite core pollutants of air
      pollution is concerned and NO as one of the main components of water-soluble ions
      has an important impact on precipitation and human health, so searching a method
      of rapid and reliable detection is an important work. According to advantages of
      the Fourier transform infrared spectroscopy technology, the infrared spectrum of
      NO3- in NH4NO3 was compared with PM2.5 by a sampling method of making film. The
      result shows that their spectra are consistent with each other. A range of
      infrared spectra of different masses of NO3- were measured and the absorbance was
      fitted with mass, correlation and mass range of which are 0.994 8 and 7.82-73.78
      microg, respectively. According to the corresponding relationship of mass between
      solution and sample film, the FTIR of the sample film was measured directly and
      mass concentrations of NO3- in a month (between 2012-03-20 and 2012-04-20) of
      Hefei area are listed and the average is 4.1713 microg x m(-3).

PMID- 24288975
TI  - [Study on contribution factor to atmospheric .OH by O3, HONO, HCHO and H2O2 in
      spring at Mangdang Mountain, Fujian Province].
AB  - The observation was conducted in Mangdang Mountain, Nanping, Fujian Province in
      the spring of 2009. Ozone, HONO, HCHO and H2O2 which are regarded as the sources
      of .OH and other atmospheric components were measured. Mixing ratios of O3, HCHO,
      HONO and H2O2 were determined to be 4.96 x 10(-8), 3.97 x 10(-10), 2. 53 x 10(
      10) and 1.18 x 10(10) respectively, which were lower than the previous
      observation at the rural areas in Northern China. Using CMAQ, the contribution
      factors to the .OH of O3, HCHO, HONO, and H2O2 were calculated to be 57.0%, 7.7%,
      34.9% and 0.4% respectively. The photolysis of O3 was the most important source
      of OH radicals in the atmosphere. The contribution factors of O3, HCHO, and H2O2
      had a single peak during 12:00-13:00 local time. For HONO, the contribution
      factor showed fluctuations during the daytime, unlike the human living
      environment in which it peaked in the morning.

PMID- 24288976
TI  - [A review on current situations of steroid estrogen in the water system].
AB  - Steroid estrogens are a group of biologically active endocrine disruptors. An
      extremely low level of steroid estrogens is sufficient to result in reproduction
      and behavior disorders, and larval mutation of both human being and animals. The
      ecological and environmental effects of steroid estrogens should be more direct
      on organisms in water system as compared with those in other environment systems.
      Therefore, in this paper we reviewed the physical and chemical properties of some
      frequently-used steroid estrogens, and their contamination status, origins and
      transfers in water system, so as to provide a theoretical basis for developing
      estrogen removal strategies.

PMID- 24288977
TI  - [A study on the veterinary antibiotics contamination in groundwater of Jiaxing].
AB  - Liquid chromatography and tandem mass (LC-MS/MS) followed with solid-phase
      extraction (SPE) was developed for simultaneously determining four classes
      (tetracyclines, quinolones, macrolides and sulfonamides) of ten commonly used
      veterinary antibiotics in groundwater of Jiaxing city, an important pig breeding
      base in the Yangtze River Delta region. Samples were taken from 10 typical rural
      river sections and 21 main urban river sections. Results revealed severe
      pollution existed in the rural river environment. The total concentration of ten
      antibiotics was as high as 65.6-467.0 ng x L(-1), among which tetracyclines and
      sulfonamides respectively ranged in 40.8-253.0 ng x L(-1) and undetected (nd)-
      165.0 ng x L(-1), macrolides and quinolones respectively ranged in 3.1-14.68 ng x
      L(-1) and nd-14.54 ng x L(-1). By comparison, the pollution level in urban rivers
      was much lower. The total concentration of ten antibiotics ranged in 20.1 ng x L(
      1) to 61.2 ng x L(-1), among with tetracyclines varied from undetected to 44.0 ng
      x L(-1), while sulfonamides, macrolides and quinolones were respectively below
      2.7 ng x L(-1), 6.3 ng x L(-1) and 21.6 ng x L(-1).

PMID- 24288978
TI  - [Contamination characteristics of short-chain chlorinated paraffins in edible
      fish of Shanghai].
AB  - According to the local habit of eating fish, in a total of 68 samples, 8 kinds of
      different trophic levels of edible fish collected in Shanghai were determined in
      terms of concentration and distribution profile of short chain chlorinated
      paraffin (SCCPs) in muscles to investigate the pollution status of SCCPs in
      edible fish from the Yangtze River Delta region. The results indicated that the
      concentrations (dw) of SCCPs in edible fish were in the range of 36-801 ng x g(
      1). With the increase in carbon chain length, the concentration of SCCPs
      decreased. In addition, lower chlorinated (Cl6-Cl8) and shorter chain (Cl10, C11)
      congeners were the dominant chlorine and carbon homologues groups, respectively,
      contributing a total relative abundance of 61.46%-82.50% to the total abundance
      of SCCPs. The levels of SCCPs in fish of Shanghai were in the medium level
      worldwide, and the distribution pattern was in line with those of the domestic
      and foreign studies.

PMID- 24288979
TI  - [Detection of endotoxin activity in water environment and analysis of influence
      factors for TAL assay].
AB  - Endotoxins, derived from cell walls of most Gram-negative bacteria and some
      cyanobacteria, are common pyrogen and highly immunogenic molecules, and related
      to many diseases. In this paper, a detection method for endotoxin activity in
      water environment using kinetic-turbid assay of Tachypleus Amebocyte Lysate (TAL)
      was established, the influence of pH and salts on TAL assay was investigated.
      Results showed that it was favorable for TAL assay in the pH range of 6.0-8.4, at
      low pHs, inhibition results were observed and opposite results were obtained at
      high pHs. The pH should be adjusted by Tris-HCl (pH = 7.4) buffer before the
      endotoxin detection. No significant interference was shown in the detection of
      water containing NaCl, Na2SO4, CaCl2, MgCl2 and KCl with a concentration of less
      than 50 mg x L(-1), however, the inhibition occurred at the concentration up to
      1000-10,000 mg x L(-1). Only 2. 5 mg x L(-1) of FeCl, Fe2(SO4)3, AlCl3 and Al2
      (SO4)3 caused significant inhibition. Endotoxin activities of ultrapure water,
      tap water and recreational water were detected by TAL assay, and their endotoxin
      activities were < 0.06 EU x mL(-1), 0.46 EU x mL(-1) and 432. 68 EU x mL(-1),
      respectively.

PMID- 24288980
TI  - [Cellular response of freshwater green algae to the toxicity of tetracycline
      antibiotics].
AB  - Tetracycline antibiotics are a group of antibiotics which has been extensively
      used in most countries and are also the most widely used veterinary drugs and
      food additives in aquaculture and livestock industries of China. Because the
      substances are poorly adsorbed in the gut of animals and are only partially
      eliminated in sewage treatment plants, the antibiotics and their metabolites
      reach surface water where they may affect the aquatic organisms and human health.
      Herein, using green algae as test organisms, we studied the effects of
      tetracycline (TC), chlortetracycline (CTC) and deoxyteracycline (DC) on the cell
      permeability and growth inhibition of Chlorella pyrenoidosa and Scenedesmus
      obliquus. After 96 h of antibiotics exposure, the permeability of the cell
      membranes of both algae was decreased in the entire concentration range of
      doxycycline and was increased after exposure to a low concentration of
      tetracycline and chlortetracycline, then was decreased with the increase of the
      two antibiotics concentrations. The growth inhibiting effects of these three
      antibiotics on Chlorella pyrenoidosa and Scenedesmus obliquus were in an order of
      DC > TC > CTC. The ecotoxic response of Scenedesmus obliquus to tetracycline
      antibiotics was more sensitive than Chlorella pyrenoidosa.

PMID- 24288981
TI  - [Illumination's effect on the growth and nitrate reductase activity of typical
      red-tide algae in the East China Sea].
AB  - Two typical red-tide algae, Skeletonema costatum and Prorocentrum donghaiense
      were selected as studied objects. The nitrate reductase activity (NRA) and the
      growth of the two algae under different illuminations through incubation
      experiment were studied. The illumination condition was consistent with in situ.
      Results showed that P. donghaiense and S. costatum could grow normally in the
      solar radiation ranged from 30-60 W x m(-2), and the growth curve was "S" type.
      However, when solar radiation was below 9 W x m(-2), the two alga could hardly
      grow. In the range of 0-60 W x m(-2), three parameters (NRAmax, micro(max), Bf)
      increased with the increasing of light intensity, indicating that the light
      intensity can influence the grow of alga indirectly through influencing the
      nitrate reductase activity. The micro(max) and NRAmax in unite volume of
      Skeletonema costatum were higher than those of Prorocentrum donghaiense,
      indicating that Skeletonema costatum can better utilize the nitrate than
      Prorocentrum donghaiense.

PMID- 24288982
TI  - [Compare the growth of Enteromorpha prolifera under different nutrient
      conditions].
AB  - Enteromorpha prolifera (E. prolifera) tides have erupted frequently in the Yellow
      Sea and brought serious environmental problems to coastal sea since 2007. In
      order to research the influence of nutrients on E. prolifera growth, mesocosm
      experiments were carried out in the Yellow Sea in May 2012. There were 12
      mesocosms, including 9 different experimental conditions. It shows that the
      uptake ability of nutrients and the growth of E. prolifera are strong. The growth
      rate of E. prolifera reaches 82% when the nutrient level is appropriate, while
      the rate could also keep around 10% even under low nutrient conditions. When
      phosphate level is appropriate, high dissolved inorganic nitrogen (DIN)
      concentration could promote the growth of E. prolifera. Sufficient and continuous
      nutrient supplement is the material basis for outbreak of E. prolifera green
      tide. Through analyzing the amount of nutrient uptake by E. prolifera, the
      production of organics by photosynthesis could be estimated, which has a strong
      linear relationship with the increased of wet weight of E. prolifera.

PMID- 24288983
TI  - [Phytoplankton pigment patterns and community structure in the Yangtze Estuary
      and its adjacent areas].
AB  - Three cruises were carried out in the Yangtze Estuary and its adjacent areas in
      May, November, June during 2009-2010. The spatial variations of phytoplankton
      community structure were investigated based on RP-HPLC analysis of pigments and
      CHEMTAX processing of the pigment data. 21 kinds of pigments were detected, among
      which chlorophyll a, peridinin, fucoxanthin, 19'-butanoyloxyfucoxanthin, 19'
      hexanoyloxyfucoxanthin, chlorophyll b, diadinoxanthin, alloxanthin and zeaxanthin
      were the major pigments in the Yangtze Estuary and its adjacent areas.
      Chlorophyll a was the most abundant in all pigments, followed by fuxoxanthin.
      Other pigments generally contributed a minor proportion to the total pigments.
      High concentrations of fucoxanthin and peridinin were observed in May 2009 and
      June 2010, indicating blooms of diatoms and dinoflagellates. The results showed
      that the composition and distribution of phytoplankton pigments were influenced
      by environmental factors. The phytoplankton community, as determined by biomarker
      pigment concentration using HPLC and CHEMTAX, was composed mainly of diatoms,
      dinoflagellates, cryptophytes, chlorophytes, cyanobacteria, prymnesiophytes,
      chrysophytes and prasinophytes. The dominant algal groups were diatoms,
      dinoflagellates and chlorophytes in May 2009. The phytoplankton community was
      characterized by high contribution of diatoms in November 2009. Diatoms,
      dinoflagellates and cryptophytes accounted for 62.5% of chlorophyll a in June
      2010, and the relative abundance of cyanobacteria was higher in this cruise. The
      spatial variations of phytoplankton community structure featured distinct
      regionality. Diatoms, chlorophytes and cryptophytes were the main groups in the
      inshore waters, and the abundances of prymnesiophytes, chrysophytes and
      cyanobacteria were increasing from inshore to the open sea.

PMID- 24288984
TI  - [Genetic diversity of picoeukaryotic phytoplankton in the lakes along the middle
      lower reaches of the Yangtze River].
AB  - The genetic diversity of picoeukaryotic phytoplankton in the 30 lakes along the
      middle-lower reaches of the Yangtze River was studied using flow cytometry
      combined with terminal restriction fragment length polymorphism (T-RFLP). The
      objectives of this study were to confirm the variance in the genetic diversity of
      picoeukaryotic phytoplankton among the lakes and to reveal its main affecting
      factors. Though the lakes investigated tended to or already were eutrophic, T
      RFLP profiles of 18S rRNA gene fragments from picoeukaryotic phytoplankton showed
      high diversity. There were altogether 197 T-RFs detected from the lakes that we
      investigated, with 89 of them obtained in less than 3 lakes. Cluster analysis
      indicated their similarity was lower than 80%. Shannon-wiener diversity index
      showed that mesotrophic lakes contained more diverse picoeukaryotic phytoplankton
      community than eutrophic lakes. The canonical correspondence analysis revealed
      that the concentration of the total nitrogen had the most important impact on the
      picoeukaryotic phytoplankton communities (P =0. 006). The results showed that the
      genetic diversity of picoeukaryotic phytoplankton in the lakes were of great
      environmental heterogeneity and closely related to the trophic status. Two CCA
      axes can only explain 10.0% of the total variance in picoeukaryotic phytoplankton
      composition, suggesting that the evolution of picoeukaryotic phytoplankton was
      probably connected to the top-down manipulation as well.

PMID- 24288985
TI  - [Studies on seasonal variation and sources of nitrogen and phosphorus in a canyon
      reservoir used as water source].
AB  - According to a continuous survey on Shibianyu Reservoir located north of the
      Qinling Mountains which lasted for about one and a half years and a simulation
      study in laboratory, conclusions were drawn as follows. The average
      concentrations of total nitrogen (TN) and total phosphorus (TP) were 2. 67 mg x
      L(-1) and 0.04 mg x L(-1), respectively, and the highest values were recorded in
      the high flow period followed by the median water period, while the lowest values
      were found in the dry period. The reservoir was in severe eutrophication and the
      content of chlorophyll a and algal cell density reached 50 mg x m(-3) and 10,000
      x 10(4) cells x L(-1), respectively. The yearly input and output of TN was
      respectively 203.1 t and 181.3 t, while the yearly input and output of TP was
      respectively 4. 2 t and 4.1 t. Exogenous pollution accounted for more than 90% of
      the total load. The sediment in reservoir showed an accumulation tendency all
      year round and the net annual accumulation of TN and TP was 20.2 t and 0. 8 t,
      respectively. The key of controlling reservoir pollution is to control the
      endogenous pollution.

PMID- 24288986
TI  - [Characteristics of sediment phosphorus in the Jiulong River-Reservoir system and
      its ecological significance].
AB  - Sediment phosphorus (P) content and component ratio from 16 sites along the North
      Jiulong River-reservoir system were analyzed using the Standard Measurement and
      Test (SMT) procedure. The spatial pattern and characteristics of sediment P and
      its ecological significance in the Jiulong River-reservoir system were examined
      in combination with water measurement and watershed information. Total P content
      in sediments ranged from 387 to 2092 mg x kg(-1) with an average of 1032 mg x kg(
      1). Inorganic phosphorus (IP) dominated P in sediment, accounting for 48%-98% of
      TP, and Fe/Al-bound phosphorus (Fe/Al-P) took 43%-99% of IP. The spatial pattern
      of sediment showed that TP and Fe/Al-P were higher in upstream and lower in
      downstream, corresponding to the spatial variation of surface water P and land
      based loads from animal waste, human waste and fertilizer loss. Spatial variation
      of TP in sediment was controlled by Fe/AI-P along the North Jiulong River. The P
      rich sediment with a great release potential due to the high ratio of Fe/ Al-P,
      the typical spatial pattern, and the lower N/P ratio observed in upstream water
      (where phytoplankton growth tends to be weakly limited by phosphorus), are likely
      to explain the fact that algal blooms first appear in the upstream and then
      spread to downstream reservoirs along the North Jiulong River. Present findings
      concerning sediment P characteristics indicate an important regulating effect and
      the ecological significance on the process of algal blooms in the Jiulong River.

PMID- 24288987
TI  - [Variation of nitrogen during the high suspended sediments concentration water
      supply in an artificial shallow lake].
AB  - The effect of water quality and suspended sediments in the process of water
      supply is of an increasing concern recently in an artificial shallow lake. The
      water supply from the Yellow River to Dongchang Lake happened on April 23rd to
      25th, 2012. The synchronous monitoring of flow velocity, suspended sediment
      concentration, dissolved nitrogen and particulate nitrogen concentration was
      conducted during the three days in five monitoring sites of the longitudinal
      profile from inlet to outlet. The spatio-temporal variation of nitrogen and the
      relationship between nitrogen concentration and suspended sediment concentration
      was analyzed. Moreover, the analysis of different nitrogen forms in surface water
      and bottom sediment was also made in the whole lake before and after the water
      supply. Results showed that the process of water supplement had an obvious effect
      on flow velocities and suspended sediment concentrations around the inlet area.
      The influence area was a limited scope. The spatial distribution of nitrogen
      presented a certain concentration gradient along the flow direction. Around the
      water inlet, concentrations of all nitrogen forms in water and bottom sediment
      was higher than those in other lake zones. The amplitude of variation of all
      nitrogen concentrations in surface water, suspended sediments showed a decreasing
      trend from water inlet to outlet. And concentrations of total dissolved and
      particulate nitrogen increased at different ratios after water supply in the
      lake. Total particulate nitrogen concentration increase was higher. It revealed
      the water supply of the Yellow River had a great influence on lake water. The
      dissolved nitrogen was the main nitrogen form in water supply. The ratio of total
      dissolved nitrogen to particulate nitrogen was 7.3 : 1. Nitrate was the primary
      form in dissolved nitrogen, and ammonium was the primary form in particulate
      nitrogen, respectively. The correlation between concentration of suspended
      sediments and ammonium, total nitrogen were notable during te water supply, the
      correlation coefficient were 0.868 and 0.876. Ammonium was mainly influenced by
      water supply and adsorption and precipitation of suspended sediments. However,
      the concentration of nitrate was not influenced. Organic nitrogen was the main
      form in bottom sediment. It meant that the Yellow River water and suspended
      sediments were the input sources of nitrogen to Dongehang Lake.

PMID- 24288988
TI  - [Limestone and pyrite-limestone constructed wetlands for treating river water].
AB  - Polluted river water was treated with limestone and pyrite-limestone subsurface
      horizontal constructed wetlands. The aims were to know the performance of two
      wetlands on removal of common pollutants, especially nitrogen and phosphorus, and
      analyze the actions of these minerals. The relationship between hydraulic
      retention time and purification performance of two constructed wetlands was
      studied. The optimal hydraulic retention time for pollutant removal was about 3
      d, The average removal efficiency of COD, TN and TP were 51%, 70% and 95%,
      respectively. With same influent and hydraulic loading, the average removal
      efficiency of COD, NH4+ -N, TN and TP were 53.93%, 82.13%, 66%, 50.9%, and
      51.66%, 77.43%, 72.06%, 97.35% for limestone and pyrite-limestone constructed
      wetlands, respectively. There were few differences between limestone and pyrite
      limestone wetlands on COD removal, but the nitrogen and phosphorus removal of
      pyrite-limestone constructed wetland was higher than that of limestone
      constructed wetland. The phosphorus removal of pyrite-limestone wetland was more
      efficiency and stable, not affected by temperature.

PMID- 24288989
TI  - [Dynamics of carbon, nitrogen and phosphorus storage of three dominant marsh
      plants in Hangzhou Bay coastal wetland].
AB  - Salt marshes perform important ecosystem functions in carbon, nitrogen and
      phosphorus recycling. The plant biomass, content and pools of C, N and P were
      measured seasonally in three marsh species Phragmites australis, Spartina
      alterniflora and Scirpus mariquezer in Hangzhou Bay coastal wetland for the
      dynamics of C, N and P storage. The results showed that seasonal variation of
      aboveground biomass displayed a unimodal curve. The seasonal variability of plant
      OC content in the aboveground part of the plants was not significant, while the
      TN and TP content decreased significantly from spring to winter. The seasonal
      variability of plant C, N and P pools was significant. And there was a
      significant relationship between plant C/N/P pools and biomass. The pools among
      plant species were significantly different. S. mariqueter had the lowest C/N/P
      pools. TN pool in the aboveground part of P. australis was higher than that of S.
      aterniflora, but its TP pool was lower than that of S. alterniflora, and there
      was no significant difference for OC pools between P. australis and S.
      alterniflora. C fixation of the three marsh species was 380%, 376% and 55.5% of
      the average C fixation of terrestrial vegetations in China, and 463%, 458% and
      67.7% of the average C fixation of terrestrial vegetations of the world.
      Considering the purification capacity of N and P, July would be the best harvest
      time of the study area for three plants. And the harvest of S. alterniflora could
      remove the biggest amount of P, since P was a limiting nutrient for phytoplankton
      growth. In conclusion, the marsh plants had strong C fixation and N/P
      purification ability.

PMID- 24288990
TI  - [Dissolved organic matter release of Zizania caduciflora and Phragmites australis
      from Lake Dianchi].
AB  - Ground dry leaves of two emerged macrophytes Zinania Caduciflora and Phragmites
      australis from Lake Dianchi were soaked in distilled water in laboratory to track
      their DOM release process. The results showed that: (1) during soaking,
      concentration of DOM which was released to the overlying water by the two species
      increased at first, then decreased and increased again at last. Concentrations of
      DOC, DON, and DOP released by both species reached their peaks at the 8th, 8th,
      and 24th hour, respectively; (2) the two species showed the same DOM release
      trend, i.e., release rates and intensities of DOC, DON, and DOP by both species
      reached the peaks at the 8th hour, and for both of them, the release rates and
      intensities of DOC, DON, and DOP at the 8th hour followed the order of DOC > DON
      > DOP; (3) the SUVA254 value obtained by the UV-visible spectroscopy increased at
      first and then decreased; (4) Fourier transform infrared (FT-IR) spectroscopy
      showed that the characteristic peak -OH disappeared during the decomposition
      process; (5) intensity of the humic-acid fluorescence peak as showed by the 3D
      EEM fluorescence intensity (F/DOC) increased along with degradation.

PMID- 24288991
TI  - [Influence of tap water treatment on perfluorinated compounds residue in the
      dissolved phase].
AB  - To study the perfluorinated compounds (PFCs) residues through water treatments
      including flocculation, sedimentation, sand filtration, ozonation with activated
      carbon and chlorination, as well as the seasonal variation of PFCs in the raw
      water of waterworks, 13 PFCs species in the dissolved phase of raw water,
      finished water, as well as the water samples after flocculation, sedimentation,
      sand filtration, and ozonation with activated carbon filtration were measured by
      the high performance liquid chromatography-tandem mass spectrometry combined with
      solid phase extraction. Results indicated that sigma PFCs residue in water was
      higher in spring and summer than that in fall and winter. The vast majority of
      PFCs in samples were of short and medium chains (C < or = 10), and
      perfluorooctane sulfonate was the most typical residue species. Among the five
      water treatment stages, sedimentation, sand filtration and ozonation with
      activated carbon filtration can remove PFCs, while flocculation and chlorination
      significantly raise the levels of short- (C < or = 6) and medium-chain (10 > or =
      C > or = 7) PFCs, respectively, causing sigma PFCs increase in finished water by
      10%-44% compared to raw water. However, the PFCs residues in finished water are
      still far below their limit values, posing no threat against human health.

PMID- 24288992
TI  - [Study on chlorinated disinfection byproducts and the relevant health risk in tap
      water of J City].
AB  - J City lies in the downstream of Taihu Lake and its water source was micro
      polluted by the well-developed industry and agriculture inside the city and in
      the upper stream. Tap water of J City is characterized as high concentrations of
      organics and ammonia nitrogen, and chlorinated disinfection byproducts (CDBPs),
      which has drawn many public concerns for the health risk. Tap water was sampled
      in May, August, October of 2012 and January of 2013. Four trihalomethanes (THMs)
      and five haloacetic acids (HAAs) were determined with the gas chromatography.
      Results revealed that THMs accounted for 88.1% of the sum of THMs and HAAs, with
      higher concentrations in May, August and January (39.34, 50.37 and 28.02 microg x
      L(-1), respectively) while obviously lower in October (19.19 microg x L(-1)),
      which were significantly higher than that of HAAs (2.58-4.02 microg x L(-1)).
      After boiled for three minutes, THMs were removed over 92.3% but HAAs were
      largely increased. The health risk of CDBPs was then calculated based on the
      health risk assessment model recommended by the USEPA. The health risk caused by
      carcinogenic CDBPs was within a range of 3.1 x 10(-6) - 7. 3 x 10(-6) in the tap
      water, all over the recommended level of 1 x 10(-6), but after boiled, the value
      significantly decreased to 7.9 x 10(-7), which is below the recommended level.
      The health risk caused by non-carcinogenic CDBPs absolutely increased from 2.1 x
      10(-11) to 3.4 x 10(-9) after boiled, which is below the reference value of 10(
      5).

PMID- 24288993
TI  - [Effect of the change in sulphate and dissolved oxygen mass concentration on
      metal release in old cast iron distribution pipes].
AB  - To understand the processes of corrosion by-product release and the consequent
      "red water" problems caused by the variation of water chemical composition in
      drinking water distribution system, the effect of sulphate and dissolved oxygen
      (DO) concentration on total iron release in corroded old iron pipe sections
      historically transporting groundwater was investigated in laboratory using small
      scale pipe section reactors. The release behaviors of some low-level metals, such
      as Mn, As, Cr, Cu, Zn and Ni, in the process of iron release were also monitored.
      The results showed that the total iron and Mn release increased significantly
      with the increase of sulphate concentration, and apparent red water occurred when
      sulphate concentration was above 400 mg x L(-1). With the increase of sulfate
      concentration, the effluent concentrations of As, Cr, Cu, Zn and Ni also
      increased obviously, however, the effluent concentrations of these metals were
      lower than the influent concentrations under most circumstances, which indicated
      that adsorption of these metals by pipe corrosion scales occurred. Increasing DO
      within a certain range could significantly inhibit the iron release.

PMID- 24288994
TI  - [Research on low-level Hg(II) removal from water by the heavy metal capturing
      agent].
AB  - Treatment of mercury containing wastewater using conventional approach is
      considered to be difficult to bring down its concentration to meet the discharge
      standard. In this study, we utilized dithiocarbamate (DTCR-2), 2,4,6
      trimercaptotriazine(TMT-18B), Na2S and Ca(OH)2+ as the advanced treatment agents
      to remove low-level Hg2+ from water. Due to its better treatment effect, DTCR-2
      was finally chosen as the most ideal option. The influence of pH value, dosage of
      DTCR-2, reaction time, initial Hg2+ concentration as well as other heavy metal
      ions on the Hg2+ removal were studied. The results showed that DTCR-2 had high
      removal efficiency under the following conditions: 100 microg x L(-1) of initial
      Hg2+ concentration, pH 8.0, 1.0 times stoichiometric ratio of DTCR-2 dosage and
      10 min of reaction time, leading to 41.36 microg x L(-1) of residual Hg2+
      concentration which was below the national discharge standard (50 microg x L(
      1)). Moreover, three heavy metal ions including Cd2+, Pb2+ and Cu2+, inhibited
      the DTCR-2 capturing capacity towards Hg2+ and the inhibition effects followed
      this order: Cu2+ > Pb2+ > Cd2+, while Zn2+ promoted the Hg2+ removal. From this
      study, we could provide theoretical support for process design to deal with
      wastewater containing low mercury concentration using DTCR-2.

PMID- 24288995
TI  - [Coagulation characteristics of polyferric chloride-poly (epichlorohydrin
      dimethylamine) composite flocculant for simulated water treatment].
AB  - Polyferric chloride (PFC) and poly (epichlorohydrin-dimethylamine) [P(EPI-DMA)]
      were applied as raw materials to prepare a novel inorganic-organic flocculant
      [PFC-P(EPI-DMA)] with various intrinsic viscosities (eta), basicity (B, OH/Fe
      molar ratio), and organic component fractions [omega(E)]. The PFC-P(EPI-DMA)
      prepared was then evaluated for the coagulation treatment of synthetic active
      dying wastewater and simulated ground water. Effects of B, and omega (E) on the
      Fe speciation distribution and coagulation performance of PFC-P(EPI-DMA) were
      comparatively examined as a function of coagulant dosage. The coagulation
      mechanism of PFC-P(EPI-DMA) was also discussed in this paper. Experimental
      results indicated the interaction effect of PFC and P (EPI-DMA) component in
      composite PFC-P (EPI-DMA). The effective Fe speciation content of PFC-EPI-DMA
      decreased with increasing omega(E), while it was maximized when eta = 850 mPa x
      As B value increased gradually, the Fe(b) concentration initially increased and
      then decreased, but the Fe(c) concentration kept continuously increasing. To some
      extent, higher eta and lower B value was favorable for the improvement of
      coagulation performance for coagulation treatment of both synthetic dyeing
      wastewater and simulated ground water. The omega (E) influence on the coagulation
      performance of PFC-P(EPI-DMA) was related to the treatment target. Both charge
      neutralization and adsorption bridging effect played roles in the coagulation
      process of the composite PFC-P(EPI-DMA).

PMID- 24288996
TI  - [Microstructure morphology and flocculation mechanism of the decolorizing
      flocculant poly-aluminum (III)-magnesium (II)-sulfate].
AB  - Crystal structures and morphologic characteristics of poly-aluminum (III)
      magnesium (II)-sulfate (PMAS) were discussed using X-radial diffraction and
      infrared spectrogram and the flocculation mechanism was explored here based on
      comparisons between decolorization effect of landfill leachate secondary effluent
      and the system Zeta potential. The results indicated that PMAS was a kind of
      macromolecular composite polymer of aluminum and magnesium based on -OH bonding.
      The flocculation mechanism of PMAS was mainly charge neutralization and co
      precipitation netting. Charge neutralization was the main mechanism at low dose.
      Its flocculation behaviors were different along with different pH of wastewater
      at high doses, namely, it was mainly charge neutralization at low pH and co
      precipitation netting at high pH and both of them work together at neutral
      condition.

PMID- 24288997
TI  - [Efficient degradation of tetrabromobisphenol A in water by co-doped FiFeO3].
AB  - Co-doped BiFeO3 was synthesized by the sol-gel method and used as a catalyst of
      persulfate (PMS) for the degradation of tetrabromobisphenol A (TBBPA). The
      effects of the amount of oxidizing agent, catalyst dosage, and the content of
      doped Co on the degradation of TBBPA were investigated. Under the optimized
      conditions (doping level of Co to Fe 0.1, dosage 0.5 g x L(-1), PMS concentration
      2.5 mmol x L(-1)), the degradation removal of TBBPA within 60 min achieved more
      than 95%. Catalyst activity showed only a little loss after 4 recycles, and
      atomic absorption spectrometry (AAS) result showed that few Co ions were leached
      (0.27% of total Co). The catalyst can be recycled with magnet which shows a good
      application prospect in the wastewater treatment.

PMID- 24288998
TI  - [Preparation bimetallic heterogeneous Fenton-like catalyst as sepiolite supported
      and its surface chemical characterization].
AB  - The reactive brilliant blue was chosen as the probe pollutant. Fe(NO3)3
      concentration, MnSO4 concentration, urea concentration, water bath temperature,
      calcined temperature and time were as influencing factors, the process parameters
      of homogeneous precipitation method was optimized for the preparation of
      bimetallic heterogeneous Fenton-like catalyst as modified sepiolite supported. At
      the same time, surface chemical characteristics of catalyst were analyzed by SEM,
      FTIR and XRD. Results showed that: with increasing iron ion concentrations, the
      active ingredient of the catalyst increased. Adding small amount of manganese ion
      could inhibit the growth of Fe2O3 diameter and increase the activity of the
      catalyst. Urea concentration was increased, so that the higher the urea
      concentration, the higher rate of formation of crystal gains, was conducive to
      generate small and uniform particles. The optimal conditions were found for
      preparing bimetallic heterogeneous Fenton-like catalyst by Box-Behnken
      experiment, which were as follows: concentration of Fe(NO3)3, MnSO4 and urea were
      0.18 mol x L(-1), 0.05 mol x L(-1) and 1.0 mol x L(-1), respectively. The dosage
      of the modified sepiolite was 40 g x L(-1) and water bath temperature was 100
      degrees C. Additionally, the catalyst was calcined at 370 degrees C for 3 h. The
      SEM showed that the sepiolite was an a-type sepiolite, which could be used as a
      well catalyst support. The infrared spectrum presented the bend vibrations of the
      Fe-O stretch vibration. The XRD patterns of the catalysts showed the
      characteristic diffraction peaks of alpha-Fe2O3, and gamma-Fe2O3.

PMID- 24288999
TI  - [Nitrite denitrification characteristics with redox mediator].
AB  - This study optimized the nitrite degradation conditions and explored the
      characteristics of nitrite degradation with redox mediators and nitrite
      denitrifying bacteria. The results suggested that the optimal condition of
      nitrite denitrification was 35 degrees C, pH = 8.0, sodium succinate as the
      carbon source, the C/N rate of 4 and the initial nitrite concentration of 100 mg
      x L(-1); the optimal AQS concentration was 0. 16 mmol x L(-1); ORP values
      stabilized around -400 mV to -500 mV with AQS, which were lower than that of
      controls during the denitrification process; the pH changed with nitrite removal
      and stabilized at 9 to 10; through the analysis of denitrifying intermediate
      metabolites, the impact of AQS on nitrite denitrifying process presumably not
      only played a coenzyme CoQ role but also accelerated the cytochrome transfer
      electronic process. This study provides the optimal parameters for practical
      application of the nitrite biodegradation with redox mediator.

PMID- 24289000
TI  - [Advanced nitrogen removal using innovative denitrification biofilter with
      sustained-release carbon source material].
AB  - An innovative denitrification biofilter was developed with polycaprolactone (PCL)
      as the carbon source and biofilm carrier. The performance of nitrogen removal was
      investigated with biologically treated effluent from secondary clarifier, and the
      results indicated that a maximum TN removal efficiency of 98.9% was achieved
      under the following conditions: influent total nitrogen (TN) concentration 30.0
      mg x L(-1), denitrification load 54.0 mg (L x h)(-1), operating temperature 20. 1
      22.0 degrees C, hydraulic retention time 0. 5 h; the total organic carbon (TOC)
      in effluent was 6.5-8.4 mg x L(-1), which was increased by 2.0-3.0 mg x L(-1)
      compared with that in the influent; the suspended solids (SS) concentration was
      less than 4.0 mg x L(-1) during operation; nearly 84.2% of the total released
      organic carbon which was used as electron donor in the denitrification process,
      was derived in the presence of microbes. The surface of the PCL pellets was
      observed by scanning electron microscope (SEM), it was shown that thick biofilm
      was formed on the surface of pellets, and the main microbial species were
      Bacillus and Trichobacteria.

PMID- 24289001
TI  - [N2O production in nitrogen removal by micro-expansion of granular sludge].
AB  - Controlled low dissolved oxygen (DO) in a sequencing batch reactor (SBR) was used
      to study the realization of micro-expansion of aerobic granular sludge, and the
      removal efficiency of COD and NH4+ -N as well as the production of the greenhouse
      gas N2O by the micro-expansion of granular sludge was investigated. The results
      showed that under the condition of low dissolved oxygen micro-expansion of sludge
      could be achieved, and the sludge volume index (SVI) was mostly in the range of
      150-250 mL x g(-1). The micro-expansion of granular sludge did not have
      significant influence on the removal of COD and NH4+ -N. The COD removal rate
      increased from 89.45% to 90.99%, the NH4+ -N removal rate decreased from 77.29%
      to 68.29%, and the nitrification rate dropped from 38.95 x 10(-3) mg (g x min)(
      1) to 33.46 x 10(-3) mg x (g x min)(-1). The micro-expansion of granular sludge
      had a big influence on the production of N2O, and the N2O production by the micro
      expanded granular sludge was 2.42 mg x m(-3), which was 1.26 times of the N2O
      production of the granular sludge without micro-expansion. The N2O release rate
      in the micro-expanded granular sludge increased from 3.63 x 10(-3) mg x (L x
      min)(-1) to 4.72 x 10(-3) mg x (L x min)(-1).

PMID- 24289002
TI  - [Sludge dewaterability with combined conditioning using Fenton's reagent and
      CPAM].
AB  - The moisture of sludge significantly influenced its dewaterability and the
      disposal cost. Cationic polyacrylamide (CPAM) and Fenton's reagent were
      investigated for sludge dewatering with separate and combined conditioning.
      Several parameters were used to evaluate the dewatering performance and to
      analyze the conditioning mechanism, such as cake moisture, soluble COD, protein
      and polysaccharide contents in supernatant and sludge particle size. The results
      indicated that favorable dewaterability was achieved when the sludge was
      conditioned at higher CPAM degrees, and sludge dewatering ability was further
      improved at acidic conditions. In Fenton reaction, higher H2O2 dosages enhanced
      the dewatering performance of sludge. Combined conditioning using Fenton's
      reagent and CPAM led to considerable improved sludge dewaterability. At the
      optimized dosages of FeSO4 (2 g x L(-1)) and H2O2 (6 g x L(-1)), the sludge
      moisture declined to 76.7% from 85.5% (raw sludge), while a moisture as low as
      74.8% was obtained by combined conditioning using CPAM (3 kg x t(-1)). Sludge
      particle size went down and the specific surface area grew bigger after Fenton
      reaction. As a result of disintegration of extracellular polymeric substances
      (EPS), the adsorbed and intrinsic water were released from microorganisms and
      sludge flocs. CPAM addition remarkably promoted the coagulating and flocculating
      of dispersed flocs. Sludge particle size changed from 35.16 microm to 50.50
      microm, and the specific surface area declined from 0.39 m2 x g(-1) to 0.20 m2 x
      g(-1). The combined conditioning using Fenton's reagent and CPAM was proved to be
      more effective in improving sludge dewaterability, compared with the separate
      conditioning.

PMID- 24289003
TI  - [Kinetic characteristics of high-rate ANAMMOX granules].
AB  - The high-rate ANAMMOX granules (HAG) were cultivated in an ANAMMOX upflow
      anaerobic sludge blanket (UASB) reactor. The kinetic characteristics of the HAG
      were investigated through batch tests, using flocculent ANAMMOX sludge (FAS) as a
      control. The results suggested that the specific ANAMMOX activity (SAA) of the
      HAG reached as high as 2.63 kg x (kg x d)(-1), which was 2.5 times of that of
      FAS. The half saturation constants for ammonium and nitrite of the HAG were 17 mg
      x L(-1) and 19 mg x L(-1), respectively, both were lower than those of the FAS.
      The half inhibition constants of ammonium, free ammonia and nitrite were
      11,679,505 and 735 mg x L(-1), respectively, which were far higher than the
      corresponding values of the FAS. The better kinetic performance of the HAG
      contributed to the successful competition of substrates under tough conditions,
      which was helpful for the novel biomass supplementation process for enhancement
      of the ANAMMOX performance.

PMID- 24289004
TI  - [Monitoring nitrogen deposition on temperate grassland in Inner Mongolia].
AB  - Nitrogen deposition on temperate steppe was monitored from November 2011 to
      October 2012 in Taipusi County, Inner Mongolia. The dry deposition of gaseous
      nitrogen compounds was calculated based on online-monitored atmospheric
      concentrations of NH3 and NO2 and dry deposition velocity simulated by CMAQ
      model. The wet deposition, dry deposition of particle, and throughfall deposition
      were also estimated by collecting rainfall, dust fall, and throughfall samples
      and the chemical analysis of NH4+ and NO3-concentrations. Results showed that the
      total deposition of nitrogen was up to 3.43 g x (m2 x a)(-1), which might be
      harmful to the ecosystem. The wet deposition accounted for about 44% of the total
      deposition, while dry deposition of gases and particle accounted for 38% and 18%,
      respectively. Since the deposition contributed more than wet deposition, a great
      attention should be paid on dry deposition monitoring. However, the very simple
      method for total deposition monitoring based on throughfall seemed not suitable
      for grassland because the monitored throughfall deposition was much lower than
      the total deposition. In addition, reduced nitrogen (NH4+ and NH3) contributed to
      71% of the total deposition, while oxidation nitrogen (NO3- and NO2) was only
      29%. Therefore, NH3 emission reduction should be considered as important as
      nitrogen oxides (NO3x) for controlling nitrogen deposition.

PMID- 24289005
TI  - [Non-point loads of soluble cadmium by in situ field experiment with different
      landuses, in central Hunan province mining area].
AB  - Non-point source loads of heavy metals from contaminated soil has increasingly
      become the major cause of heavy metal concentrations of rivers and lakes
      surpassed the limitation value, while only few studies had focused on
      quantitative monitoring of soil heavy metal transportation to water, in situ
      field conditions. As reported, agricultural farmland heavy metal contamination
      was the major contamination problem, especially for cadmium (Cd) pollution in
      middle and downstream of Xiangjiang River. This study selected the typical Cd
      polluted agricultural watershed for a case study, three typical landuse types of
      rice, dry farmland and unused grassland with three replicate quadrates were
      carried out for natural rainfall runoff hydrology processes monitoring, from 2011
      2012. Results showed that, precipitation pH value increased from spring to
      summer, soluble Cd concentration of spring runoff was significantly higher than
      that of summer rainfall runoff, which presented an obviously seasonal
      heterogeneity and had a negative correlation with rainfall pH value, and rainfall
      pH value can obviously impact soil soluble Cd transportation into surface runoff
      charge. In the same rainfall event, soluble Cd concentration and non-point load
      of rice were significantly lower than those of dry land and unused grassland,
      while no obviously seasonal trend was found for non-point load of Cd from three
      typical landuse types because of the rainfall depth variance, which needs more
      researches and concerns in the future. These results can provide valuable data
      and scientific supports for watershed scale's heavy metal non-point source load
      quantitative estimation and water environment management and water quality
      diagnosis and early warning.

PMID- 24289006
TI  - [Heavy metal speciation and stability in the sediment of Lihu Lake].
AB  - The spatial occurrence characteristics of the speciation of Cr, Ni, Cu, Zn, As,
      Cd, Hg and Pb in sediments of the lake body and river mouths of Lihu Lake were
      studied. Meanwhile, combined with the spatial distribution of metals in
      interstitial water, the stability and bio-availability of various forms of
      studied metals were discussed. The results showed that metals in interstitial
      water and extractable metals in surface sediments both had obvious spatial
      heterogeneity, and the metal contents in retreated fishery district were lower.
      High value areas of Cr, Cu and Zn distributed in belt along Baojie Bridge and
      Lihu Lake Bridge, and the high value areas of Ni, As, Cd, Hg distributed in
      sector extending from river mouths to the lake body. Most metals mainly existed
      in residue state except for Cd, Cu and Ni, the extractable content of which
      respectively accounted for 71.02%, 54.79% and 50.62% of the total content. The
      stability of eight studied metals was in the order of Cr > Pb > Hg > As > Cu > Ni
      > Zn > Cd. Cd and Zn were unstable in most studied sites, so there was higher
      risk of quick desorption and release. Toxicity assessment of interstitial water
      showed that the tested metals would not pose acute toxicity for aquatic
      ecosystem, but Hg and Pb in some districts, especially in the river mouths, might
      pose chronic toxicity for the benthonic organisms.

PMID- 24289007
TI  - [Analysis and evaluation of heavy metals along the Chaohe River in Miyun County].
AB  - In order to explore the heavy metal concentrations in soils surrounding the
      Chaohe River, 15 soil samples were collected along the Chaohe River. Results show
      that average concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, Zn are 7.94, 0.16,
      127.71, 38.45, 0.22, 45.97, 21.98, 81.06 microg x g(-1), respectively. The mean
      concentrations of 15 samples for most heavy metals are higher than the background
      values of Beijing soil except Pb. Compared to the heavy metal concentrations in
      the soil of Shanghai Huangpu River water resource area, the mean concentrations
      of Cr, Cu and Ni are higher and concentrations of other heavy metals are at a
      moderate level. Geo-accumulation index method was used to evaluate the pollution
      status of different heavy metals. Results show that the pollution of Cr and Hg is
      moderate. The pollution of Cu and Ni is between no to moderate. There is no
      pollution of As, Cd, Pb and Zn in the study area. Ecological risk index method
      was also used to evaluate the ecological impact. Results show that the pollution
      level of Hg is strong and Cu is medium. Other heavy metals are at a slight
      pollution level. The samplings region as a whole is at a medium ecological
      pollution level. In a word, Hg, Cr, Ni, and Cu need to be controlled.

PMID- 24289008
TI  - [Magnetic properties of topsoils in typical industrial belt along the Yellow
      River in arid regions in northwest China and their environmental significance].
AB  - We have carried out environmental magnetic investigation on topsoil samples of
      two industrial cities Wuhai and Shizuishan along the Yellow River in the arid
      regions in northwest China. The concentration, type, magnetic grain sizes of the
      magnetic minerals and the environmental significance were discussed. The results
      showed that the main magnetic grain sizes were multi-domain (MD) and pseudo
      single domain (PSD). The concentration and grain sizes of magnetic minerals
      showed differences in different functional zones. In industrial zone, the
      concentration was higher and the grain size was coarser, while there were
      obviously fewer and finer magnetic minerals in agricultural zone and raw coal
      zone. Environmental magnetic measurements were efficient to monitor pollution
      caused by burned fossil fuel, but were not sensitive to unburned fuel. X,, SIRM
      and SOFT were effective indicators to reflect urban soil pollution. Environmental
      magnetism method was found to be an important way to monitor and evaluate soil
      pollution in a city.

PMID- 24289009
TI  - [Study on composite stabilization of arsenic (As) contaminated soil].
AB  - Since the contaminated soil may contain various kinds of heavy metals, use of
      single chemical reagent leads to poor remediation and high cost. In this study,
      soil containing As, Zn, Cd was sampled, and different reagents were selected to
      carry out the rapid stabilization of contaminated soil. The TCLP (toxicity
      characteristic leaching procedure) was used to evaluate the leachate toxicity of
      heavy metals and the results indicated that calcium-containing, sulphur
      containing and iron-containing reagents had good performance in reducing the
      metal mobility. The stabilization efficiency of the six reagents tested ranked in
      the order of CaO > Na2S > organic sulfur > Chitosan > FeSO4 > (C2H5)2NCS2Na. Two
      types of reagents (six reagents) were combined based on the target properties of
      different reagents and the stabilization efficiency was evaluated and analyzed.
      The results indicated that the composite reagents had higher stabilization
      efficiency: the efficiency of 3% FeSO4 + 5% CaO was 81.7%, 97.2% and 68.2% for
      As, Cd and Zn, respectively, and the efficiency of 3% CaO + 5% organic sulfur was
      76.6%, 95.7% and 93.8% for these three metals, respectively. Speciation analysis
      was carried out in this study and the results suggested that it was the change of
      metals from the exchangeable state to the reduction (for inorganic reagent) or
      oxidation state (for organic reagent) that caused the soil stabilization and the
      degree of change determined the stabilization efficiency.

PMID- 24289010
TI  - [Heavy metal contents and enrichment characteristics of dominant plants in a lead
      zinc tailings in Xiashuiwan of Hunan Province].
AB  - The key of phytoremediation was researches and selecting of dominant species in
      the lead-zinc tailings. This assay analyzed the amount of heavy metals, and the
      enrichment and transporting features of heavy metals, such as Pb, Zn, Cu, Cd and
      Mn, in the dominant species in the district, and then we can select the pioneer
      plants for ecosystem restoration of the area. Results showed that there were 40
      species of higher plants, which belonged to 40 chasses and 22 families in the
      area. And we selected 15 dominant species by heavy metals. Among these dominant
      species, the content of Pb in Ficus tikoua was 4. 01 times higher than that in
      other plants, the transfer factor (TF) was 3.91, and bioaccumulation factor (BCF)
      was 14.4. The capability of TF and BCF of Ficus zikoua was high, so Ficus tikoua
      had potentials in phytoremediation of heavy metals in polluted area and its
      enrichment capability of Pb was worth for the further research. Apart from Ficus
      zikoua, other 14 kinds of dominant plants had a better tolerance in metal
      pollution in tailings, and they can be used as pioneer plants of ecological
      rehabilitation in lead-zinc tailings in Xiashuiwan.

PMID- 24289011
TI  - [Comparison of soil fertility among open-pit mine reclaimed lands in Antaibao
      regenerated with different vegetation types].
AB  - Re-vegetation is mainly applied into regeneration in opencast mine to improve the
      soil quality. It is very important to choose feasible vegetation types for soil
      restoration. In this study, three typical forest restoration types were studied
      at Antaibao mine, namely, Medicago sativa, mixed forests Pinus taebelaefolius
      Robinia pseudoacacia-Caragana korshinskii and Elaeagnus angustifolia-Robinia
      pseudoacacia-Caragana korshinskii-Hipophae rhamnoides, to determine the nutrient
      contents and enzyme activities in different soil layers. The results showed that
      re-vegetation markedly increased soil nutrient contents and the enzyme activities
      during the restoration process. The nutrient content of soil in the P.
      taebelaefolius-R. pseudoacacia-C. korshinskii mixed forest field was
      significantly higher than those in other plots. It was found that the soil of the
      P. taebelaefolius-R. pseudoacacia-C. korshinskii mixed forest had the highest
      integrated fertility index values. In conclusion, the restoration effects of the
      P. zaebelaefolius-R. pseudoacacia-C. Korshinskii mixed forest was better than
      that of E. angustifolia-R. pseudoacacia-C. korshinskii-H. rhamnoides, while M.
      sativa grassland had the least effect.

PMID- 24289012
TI  - [Biodegradation of triphenyltin and its effect on Klebsiella pneumoniae].
AB  - To investigate the pathway and mechanism of triphenyltin (TPhT) biodegradation by
      Klebsiella pneumoniae, and the effects of TPhT on cells during the degradation
      process, the alteration of carbon utilization ability of the strain after dealing
      with different concentrations of TPhT was studied by the Biolog method, and the
      degradation pathway of TPhT was explored by GC-MS and X-ray photoelectron
      spectroscopy (XPS). After degradation for 2 h, the nutrient utilization capacity
      of K. pneumoniae was significantly improved by 1 mg x L(-1) TPhT. Atomic force
      microscope observation found that exposure to TPhT changed the cellular
      morphology, inducing the apoptosis of some cells, but most of the cells still
      maintained intact and had smooth cell wall. The efficiencies of TPhT removal by
      intracellular enzyme were up to 66.0% within 120 h, which demonstrated that
      endoenzyme was more effective than the intact cells. The results of GC-MS and XPS
      revealed that during the biodegradation process, TPhT was transformed to
      diphenyltin, monophenyltin and finally inorganic tin.

PMID- 24289013
TI  - [Isolation and degradation characteristics of dichloromethane-degradation
      bacterial strain by Methylobacterium rhodesianum H13].
AB  - A dichloromethane-degrading bacterium Methylobacterium rhodesianum H13 which
      utilized the DCM as the sole carbon and energy source was isolated. According to
      the research, M. rhodesianum H13 could completely degrade 5 mmol x L(-1) DCM in
      23 h with the initial cell concentration of 0.82 mg x L(-1), pH 7.0, 30 degrees
      C, and the cell yield rate was about 0.136 g x g(-1) DCM. With the degradation of
      DCM, Cl- concentration gradually raised (the release of Cl- concentration was
      about 2 times higher as the DCM), pH value dropped to 6.75, and the solution was
      weakly acidic. Temperature, pH, DCM concentration, Cl- concentration and other
      factors were investigated through the shake flask experiments, and the optimal
      conditions for DCM degradation were: temperature 30 degrees C, pH 7.0. The study
      also indicated that 5 mmol x L(-1) of DCM was the optimum concentration for M.
      rhodesianum H13 and high levels of DCM could inhibit the degradation. The
      research has an important application value for the DCM environmental pollution.

PMID- 24289014
TI  - [Effect of different primers on microbial community of activated sludge].
AB  - The aim of this study was to investigate the effect of different primers in PCR
      DGGE and PCR-RFLP on the analysis of microbial community in activated sludge. 8
      pairs of primers were chosen to amplify the variable region of 16S rDNA for PCR
      DGGE analysis, while 11 pairs of primers were used to amplify the total length of
      16S rDNA for PCR-RFLP analysis. The effect of different primers on the analysis
      of microbial community in activated sludge was determined by electrophoresis
      analysis of the PCR products. The microbial community of the activated sludge was
      different when different primers were used. For PCR-DGGE analysis, the primers
      B341F/B534R had good amplification results and the bands were excessive; while
      for PCR-RFLP, the primers 27f/8f and 1500R had good amplification results and the
      bands digested by the two enzymes had the highest diversity. The primers
      B341F/B534R and 27f/8f/ 1500R were relatively good for PCR-DGGE and PCR-RFLP,
      respectively, in the analysis of microbial community in activated sludge.

PMID- 24289015
TI  - [Reaction of SO2 over CaAl mixed oxides derived from hydrotalcites samples].
AB  - Series of CaAl hydrotalcite-like compounds were synthesized by co-precipitation,
      and the oxides were obtained after being calcined at 800 degrees C. XRD, BET, DTG
      and TPD were taken to characterize the physicochemical properties of samples, and
      reactions of SO2 over samples were studied. Results show that precursors were
      homogeneous and well crystallographic, and after being calcined with taking off
      the interlayer hydroxyls, water and anion, forming CaO and (CaO)x(Al2O3)y, and
      the Ca element enhances the thermal stability, Ca3AI-LDO has the largest surface
      area, the highest pore volume and the most basic center, the saturation capacity
      was 0. 29 g x g(-1) at 700 degrees C.

PMID- 24289016
TI  - [Optimization for MSW logistics of new Xicheng and new Dongcheng districts in
      Beijing based on the maximum capacity of transfer stations].
AB  - It is necessary to achieve the optimization for MSW logistics based on the new
      Xicheng (combining the former Xicheng and the former Xuanwu districts) and the
      new Dongcheng (combining the former Dongcheng and the former Chongwen districts)
      districts of Beijing. Based on the analysis of current MSW logistics system,
      transfer station's processing capacity and the terminal treatment facilities'
      conditions of the four former districts and other districts, a MSW logistics
      system was built by GIS methods considering transregional treatment. This article
      analyzes the MSW material balance of current and new logistics systems. Results
      show that the optimization scheme could reduce the MSW collection distance of the
      new Xicheng and the new Dongcheng by 9.3 x 10(5) km x a(-1), reduced by 10%
      compared with current logistics. Under the new logistics solution, considering
      transregional treatment, can reduce landfill treatment of untreated MSW about
      28.3%. If the construction of three incineration plants finished based on the new
      logistics, the system's optimal ratio of incineration: biochemical treatment:
      landfill can reach 3.8 : 4.5 : 1.7 compared with 1 : 4.8 : 4.2, which is the
      ratio of current MSW logistics. The ratio of the amount of incineration:
      biochemical treatment: landfill approximately reach 4 : 3 : 3 which is the target
      for 2015. The research results are benefit in increasing MSW utilization and
      reduction rate of the new Dongcheng and Xicheng districts and nearby districts.

PMID- 24289017
TI  - [Application of multiple lines of evidence analysis technology in the assessment
      of sites contaminated by heavy metals].
AB  - A multiple lines of evidence analysis technology was applied to assess whether
      sites were contaminated by heavy metals (HMs). Firstly, the baseline upper limit
      concentration for As and Cr6+ were derived for the two investigated sites based
      on the analysis of the relative cumulative probability plots of the two metals
      and their spatial distribution in the soil. The results indicated that the
      baseline upper limit concentrations for As and Cr6+ at site 1 were 29. 8 mg x kg(
      1) and 76. 1 mg x kg(-1), respectively, which were much higher than those
      reported for the local area by others. But at site 2, the baseline upper limit
      concentrations for As and Cr6+ were 10.6 mg x kg(-1) and 33 mg x kg(-1),
      respectively, which were only a little higher than the reported values. Taken the
      derived baseline concentrations as the assessment criteria, both sites were
      contaminated by the heavy metals to some degree, which is consistent with the
      site historical activities review results and element correlation analysis
      results. At site 1, the As concentration in 3.8% samples exceeded the derived
      baseline concentration, while the Cr6+ concentration in 6.0% samples exceeded the
      baseline concentration. At site 2, only the concentration of As in 5.2% samples
      exceeded the derived baseline value. All the above exceeding rates were much
      lower than those based on the reported baseline values, which were 77.7% and
      96.7% for As and Cr6+ at site 1, respectively and 41.9% for As at site 2. The
      difference indicates that for a specific site, the baseline concentrations for
      heavy metals reported in literatures should not be directly applied as the
      criteria to assess whether the site is contaminated or not, which may cause the
      results to lose the objectivity and leading to the misallocation of lots of rare
      resource to remediate soil that maybe not contaminated.

PMID- 24289018
TI  - [Heavy metals and their sources in outdoor settled dusts in different function
      areas of cities].
AB  - To study the distribution of heavy metals in outdoor settled dusts in different
      functional areas, based on the literature published, we described the difference
      in heavy metal accumulation in functional areas and their sources by comparing
      and analyzing the data of heavy metal concentrations in some capital cities. The
      results showed that industrial area had the highest heavy metal concentration,
      followed in descending order by residential area and commercial area, and
      finally, traffic area. The levels of Zn and Pb in the four functional areas
      showed higher spatial variability, while there was little difference in Cu and Cd
      levels. Compared to the heavy metal concentration in urban soils, industrial area
      appeared heavily accumulated and traffic area appeared lighter accumulated with
      heavy metals, while there was little difference among other three functional
      areas expect industrial area. The accumulation of Cd in the four functional areas
      showed the lowest spatial variability.

PMID- 24289019
TI  - [Study on distribution characteristics and potential ecological risk of soil
      heavy metals in the Yellow River beach region in Kaifeng City].
AB  - The distributions, soil environment status and potential ecological risk of heavy
      metals were studied in beach soil of returning the cropland into Yellow River
      beach region in Kaifeng by the Nemerows and Hakansons methods. The results showed
      that (1) as Among the average contents of the five heavy metals Pb, Cr, Hg, As
      and Cd, the highest was the average content of Cr, and the lowest was the average
      content of Pb and Hg. In addition to Hg, the coefficients of variation of other
      heavy metals were relatively small, indicating that the content of heavy metals
      was quite different at different sites, and to some extent, relecting that Hg, As
      and Pb were the major elements polluting the soil, among which, Pb pollution was
      the pollution with universality. There was little difference in the contents of
      Cr and Cd from village to village the coefficient of variation was small, and the
      contents were below the national standard level. (2) There was significant
      difference in the spatial distribution of soil heavy metal elements in the upper,
      the middle and lower sections of the study area. The upper section was clean, the
      middle section was slightly polluted, and the lower section was enriched with
      pollutants. (3) The distribution of heavy metals in the beach region inside and
      outside the levees of Yellow River was closely related to the distribution of the
      residential regions. In the upper section of the beach region (southwest), the
      population was large and the contents of heavy metals were high. The contents of
      heavy metals were lower in the near river zone than outside the levees of Yellow
      River. And the heavy metal contents in the middle and lower section were higher
      than those outside the levees of Yellow River, while the lower section
      (northwest) showed a tendency of pollution enrichment. (4) In the view of the
      average individual potential ecological risk index of heavy metals (E(r)i), the
      potential ecological risk of Hg reached intense levels, and the potential
      ecological risk of Pb's contribution to the integrated risk was 50.5%, which was
      the heavy metal with highest ecological risks. Cd and Pb had a moderate
      ecological risk, while As and Cr had minor ecological risk. Ecological hazards of
      heavy metals ranked in the ascending order of Hg > Pb > As > Cd > Cr. (5) The
      ecological hazard of the heavy metals was ranked in the order Hg > Cd > As > Pb >
      Cr. Based on the potential ecological risk level corresponding to the RI values,
      it was shown that there was moderate potential ecological risks of heavy metals
      in the Yellow River beach region in Kaifeng.

PMID- 24289020
TI  - [Study on pollution evaluation of heavy metal in surface soil of the original
      site of Qingdao North Station].
AB  - The determination of pollution extent and health risk assessment are the premise
      of heavy metal contaminated site remediation. The content of Cu, Cr, Pb, Cd, Zn,
      Ni in Qingdao North Station was detected, and the correlation of the 6 kinds of
      heavy metal content was analyzed. The pollution extent in excess of background
      values was characterized by anthropogenic influence multiple, and the pollution
      of heavy metal in soil was evaluated using geoaccumulation index and a new method
      which connects geoaccumulation index with Nemero index. Finally, human health
      risk assessment was carried out with health risk assessment model for heavy metal
      content. The results showed that Qingdao North Station soil were polluted by
      heavy metals. Six heavy metal pollution levels were: Cd > Cu > Ni > Pb > Cr > Zn,
      and Cd had reached the severity pollution level, Cu and Ni followed by, Cr, Pb
      and Zn were in minor pollution level. The order of coefficient variation in all
      heavy metals was: Cd > Ni > Cr > Zn > Pb > Cu. Within the study area soil heavy
      metal distribution was different, but overall discrepancy was small. The order of
      non-cancer hazards of heavy metals in soil was Cr > Pb > Cu > Ni > Cd > Zn, and
      the order of carcinogen risks of heavy metals was Ni > Cd. The non-cancer hazard
      and carcinogen risks values of metals were both lower than that their threshold
      values. They were not the direct threats to human health.

PMID- 24289021
TI  - [Distribution characteristics and ecological risk of Pb in soils at a lead
      battery plant].
AB  - Soil samples were collected from 18 sites at a relocated lead accumulator factory
      in the Southwest region, China. Among the 15 sample sites, profile soil samples
      at 0-20 cm, 20-40 cm and 40-60 cm were taken. Soil lead contents were analyzed by
      inductively coupled plasma-optical emission spectroscopy (ICP-OES).
      Characteristics of Pb in topsoil and soil profiles collected from different
      sampling sites were discussed. Results showed that: (1) The total Pb contents in
      topsoil (0-20 cm) ranged from 18.18 to 52,332.50 mg x kg(-1). The maximum content
      greatly exceeded the national standard (HJ 350-2007). The Pb concentration in
      different workshops followed a decreasing order: the fourth workshop > the second
      workshop > waste lead storage pit > sewage works > the third workshop > the fifth
      workshop > the first workshop > the original fourth workshop > the packing
      workshop > the office area. (2) Results of profile distribution showed that soil
      depth had no significant effect on Pb content. Lead can be highly accumulated at
      different depths of the soil, which was quite different from natural soils. (3)
      Hakanson's potential ecological risk index evaluation showed that there was
      widespread ecological risk in the soil of the plant, and serious ecological risk
      existed in some workshops where a large number of lead was enriched. Therefore,
      the site must be restored in order to reuse it.

PMID- 24289022
TI  - [Effect of lead on soil quality and human health around a lead smeltery].
AB  - In order to disclose soil pollution caused by lead (Pb) smeltery and its human
      health risks, this study investigated Pb concentrations in farmland soil, hair
      and blood of residents surrounding a Pb smeltery in Henan Province, and discussed
      the rationality of estimation of the health protection zone from the Pb smeltery.
      It was found that the Pb concentrations in blood of children living in both M and
      Y villages exceeded the international Pb poisoning diagnostic criteria. The
      highest Pb concentration in blood was 491 microg x L(-1), with the percentages of
      mild, medium and severe Pb poisoning reaching 52.5%, 42.5% and 5.0%,
      respectively. Pb concentrations in hair of children living in Y village were in
      excess of the related standard, with the highest being 156 mg x kg(-1), and the
      average value 2.9 times of that in hair of adults. In terms of Pb in soil, Pb
      concentrations in 66.7% of the topsoils (0-20 cm) around the smeltery exceeded
      Grade II (350 mg x kg(-1), pH > 7.5) of the National Soil Environmental Quality
      Standard (GB 15618-1995), with the highest reaching up to 1687 mg x kg(-1). The
      severe soil pollution may have played a role in children's health issues in the
      villages surrounding the smeltery. Therefore, more attention should be paid to
      the scientific estimation of health protection zone from Pb smeltery and the
      remediation of heavy-metal contaminated soil in the surrounding areas.

PMID- 24289023
TI  - [Distribution characteristics of lead in different particle size fractions of
      surface soil of a lead-acid battery factory contaminated site].
AB  - In this research, six topsoil samples (0-20 cm) were collected in the heavy-metal
      lead contaminated soil of one lead battery factory in south-west China as
      research object, which were later divided into seven particle size fractions, and
      analyzed for the lead concentration as well as the correlation between the lead
      concentration and the organic matter content. The result showed that five soil
      samples were contaminated with lead with different pollution levels, and there
      were two different trends in the changes of lead concentration as of the change
      of soil particle size. The lead concentration of the three samples from sewage
      treatment workshop, the workshop A and the workshop B, showed a first declining
      and then ascending trend with the decreasing particle size. The lead
      concentration of the soil samples of the packing workshop and the former
      production workshop A showed a decreasing trend when the particle size decreased.
      The lead concentration and the organic matter content showed a positive linear
      correlation (R2 = 0.8232). Soil organic matter has the ability of lead
      enrichment, and the ability declines with the decreasing particle size. Soil
      texture may be an important factor for the interaction between soil organic
      matter and lead distribution.

PMID- 24289024
TI  - [Research on the application of in-situ biological stabilization solidification
      technology in chromium contaminated site management].
AB  - In-situ biological stabilization solidification (SS) technology is an effective
      ground water risk control method for chromium contaminated sites. Through on-site
      engineering test, this paper has preliminarily validated the remediation effect
      of in-situ SS method on a southern chromium contaminated site. The engineering
      test site has an area of approximately 600 m2, and is located at the upstream of
      the contaminated area. Due to the severe contamination of chromium, the total
      chromium concentration reached up to 11,850 mg x kg(-1), while the hexavalent
      chromium concentration reached up to 349 mg x kg(-1), and the most severely
      contaminated soil had a depth of -0.5 - -2 m. Variations in hexavalent chromium
      and total chromium concentration in groundwater were observed through the
      injection of reducing agents and microbial regulators into the injection wells in
      the test site, and through the monitoring analysis at different time and
      different depth under the action of the injection agents. Results of the
      engineering test showed that the on-site SS technology significantly changed the
      chromium speciation in soil and then reduced the migration of chromium, thus the
      groundwater risk was reduced. The injected agents had a good effect of hexavalent
      chromium remediation in groundwater within the effective range of the injection
      wells, and the SS rate of hexavalent chromium into trivalent chromium reached 94%
      99.9%, the SS rate of total chromium fixation reached 83.9%-99.8%. The test
      results are of significant reference value for the remediation of contaminated
      sites with features of shallow groundwater depth and soil mainly consisting of
      silty clay and sandy clay.

PMID- 24289025
TI  - [Research on the effect and technique of remediation for multi-metal contaminated
      tailing soils].
AB  - Soil samples were collected from compound polluted tailings to analyze the
      contents of total heavy metals and their speciation in the soil. Laboratory batch
      tests were conducted to examine the effects of distilled water and different
      concentrations of oxalic acid, citric acid, acetic acid, HNO3 and EDTA on the
      removal of heavy metals from the polluted soils. The suitable eluent and its
      optimal conditions including liquid to soil ratio, reaction time and washing
      number were also optimized, and the total toxicity reduction index was proposed
      to evaluate the effect of the eluent on the remediation of polluted soil. The
      results showed that Cd and Pb were the most abundant heavy metals in the soil,
      reaching 52.2 mg x kg(-1) and 4836.5 m x kg(-1), respectively. There was
      significant difference in the removal efficiency for different heavy metals. Cr
      had a maximum removal efficiency of 2.7%, while the maximum Cd and Pb removal
      efficiency was both about 60%. Distilled water had little removal efficiency for
      heavy metals, with less than 0.1% removal rate; the heavy metal removal
      efficiency of oxalic acid and acetic acid was also quite low; EDTA in 0.1 mol x
      L(-1) was selected as the suitable eluent for the polluted soil. Evaluation of
      the total toxicity reduction index and the cost suggested that EDTA should be
      used with a liquid to soil ratio of 6:1, a reaction time of 3 h and 2 washings.

PMID- 24289026
TI  - [Analysis of washing efficiency and change in lead speciation in lead
      contaminated soil of a battery factory].
AB  - Lead-contaminated soil with different pollution load in a lead battery factory in
      the southwest of China was chosen as the research object, the lead content and
      speciation were analyzed, and different washing agents were screened. The lead
      washing efficiency and lead speciation were analyzed under different pH
      conditions, and the soil of different particle size was washed using different
      duration to determine the best washing time. The results showed that the soil of
      sites A and B in the factory was severely contaminated, the lead concentration
      reaching 15,703.22 mg x kg(-1) and 1747.78 mg x kg(-1), respectively, and the
      proportion of the active-state lead was relatively high, while the residue state
      accounted for only 17.32%, 11.64%, 14.6% and 10.2%. EDTA and hydrochloric acid
      showed the best extraction effect in the 5 washing agents tested, which included
      EDTA, hydrochloric acid, citric acid, rhamnolipid and SDS. Cleaning under acidic
      conditions could not only effectively extract the total amount of lead but also
      effectively reduce the environmental risk of active-state lead. pH 4-7 was
      suggested as the most appropriate condition. The cleaning effect of coarse sand
      and fine sand was good, while for washing powder clay, it is better to improve
      the process, with the optimal washing time determined as 240 min.

PMID- 24289027
TI  - [Remediation efficiency of lead-contaminated soil at an industrial site by
      ultrasonic-assisted chemical extraction].
AB  - This research chose five lead-contaminated sites of a lead-acid battery factory
      to analyze the speciation distribution and concentration of lead. Under the same
      conditions (0.1 mol x L(-1) EDTA,30 min, 25 degrees C), the removal effect of
      heavy metal was compared between ultrasonic-assisted chemical extraction (UCE)
      and conventional chemical extraction ( CCE), and the variation of lead speciation
      was further explored. The results showed that the lead removal efficiency of UCE
      was significantly better than CCE. The lead removal efficiency of WS, A, B, C and
      BZ was 10.06%, 48.29%, 48.69%, 53.28% and 36.26% under CCE. While the removal
      efficiency of the UCE was 22.42%, 69.31%, 71.00%, 74.49% and 71.58%, with the
      average efficiency higher by 22%. By comparing the speciation distribution of the
      two washing methods, it was found that the acid extractable content maintained or
      decreased after UCE, whereas it showed an increasing trend after CCE. The
      reduction effect of the reducible was as high as 98% by UCE. UCE also showed a
      more efficient reduction effect of the organic matter-sulfite bounded form and
      the residual form. Hence, it is feasible to improve the washing efficiency of
      heavy metal contained in soil by conducting the cleaning process with the help of
      ultrasonic wave, which is a simple and fast mean to remove lead from contaminated
      sites.

PMID- 24289028
TI  - [Parameters optimization and cleaning efficiency evaluation of attrition
      scrubbing remediation of Pb-contaminated soil].
AB  - Attrition scrubbing was used to remediate lead contaminated-site soil, and the
      main purpose was to remove fine particles and lead contaminants from the surface
      of sand. The optimal parameters of attrition scrubbing were determined by
      orthogonal experiment, and three soil samples with different lead concentration
      were subjected to attrition scrubbing experiments. The results showed that the
      optimal scrubbing parameters were: a solid ratio of 70% dry matter, a temperature
      of 25 degrees C, an attrition time of 30 min, and an attrition speed of 1200 r x
      min(-1). Before attrition scrubbing, the screening and analysis of soil showed
      that in all three soil samples, lead was mainly enriched on sand and fine
      particles, and the distribution of lead was highly correlated to the organic
      matter. After attrition scrubbing, the washing efficiency of the original state
      lead contaminated sand soil in triplicates was 67.61%, 31.71% and 41.01%,
      respectively, which indicates that attrition scrubbing can remove part of the
      fine soil and lead contaminants from the surface of sand, to accomplish the
      purpose of pollutants enrichment. Scanning electron microscopy (SEM) analysis
      showed that the sand surface became smooth after attrition scrubbing. The results
      above show that attrition scrubbing has a good washing effect for the remediation
      of lead contaminated sand soil.

PMID- 24289029
TI  - [Adsorption of Cd2+ on biochar from aqueous solution].
AB  - Biomass-based materials such as biochar have a good performance in heavy metal
      adsorption. The adsorption of Cd2+ on biochar converted from cotton straw was
      studied. Adsorption isotherm, kinetics and effect factors such as temperature, pH
      and ionic strength were investigated. The adsorption of Cd2+ on biochar can be
      fitted by the Freundlich isotherm better than the Langmuir isotherm. The maximum
      adsorption amounts of Cd2+ at different temperatures were 9.738 mg x g(-1)
      (288.15 K), 10.14 mg x g(-1) (298.15 K), 10.40 mg x g(-1) (308.15 K) and 10.71 mg
      x g(-1) (318.15 K), respectively. The free energies AG(theta) were from -8.346 kJ
      x mol(-1) to -10.276 kJ x mol(-1) at different temperatures, indicating that the
      adsorption of Cd2+ onto biochar is spontaneous and is an endothermic process. The
      adsorption process can reach equilibrium within 40 minutes and can be fitted by
      the pseudo second order kinetic model. pH showed a significant effect on the
      adsorption of Cd2+ on biochar in the range of 2-8. The adsorption amount of Cd2+
      on biochar shows a reducing trend with the increasing ionic strength.

PMID- 24289030
TI  - [Effect of inorganic amendments on the stabilization of heavy metals in
      contaminated soils].
AB  - Effects of single and mixed inorganic amendments on the stabilization of heavy
      metals in contaminated soils were investigated. Significant synergistic effects
      on the stabilization of Zn and Cu were observed with the mixed inorganic
      amendments of KH2PO4 and Ca(OH)2 in the laboratory test. In the field test, the
      stabilization ratios of Zn, Cu and Cd were 41.8%, 28.2% and 48.4%, respectively,
      with the dosage of 0.5 kg x m(-2). The growth of peanut was inhibited by the
      addition of the inorganic amendments. Meanwhile, the uptake of heavy metals was
      reduced in peanut.

PMID- 24289033
TI  - Acute exertional rhabdomyolysis.
AB  - The patient was a 21-year-old man who was serving in the military. He was
      evaluated by an orthopaedic surgeon for a chief complaint of severe pain in both
      lower extremities that began 2 days prior after performing repetitive, vigorous
      squatting exercises. Due to concern over acute exertional rhabdomyolysis,
      laboratory testing, scintigraphy, and magnetic resonance imaging were completed.
      The laboratory results and the findings seen on diagnostic imaging were
      consistent with rhabdomyolysis.

PMID- 24289031
TI  - Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11
      using the free-living nematode Caenorhabditis elegans.
AB  - With the problem of parasitic nematode drug resistance increasing, vaccine
      development offers an alternative sustainable control approach. For some
      parasitic nematodes, native extracts enriched for specific proteins are highly
      protective. However, recombinant forms of these proteins have failed to replicate
      this protection. This is thought to be due to differences in glycosylation and/or
      conformation between native and recombinant proteins. We have exploited the free
      living nematode Caenorhabditis elegans to examine its suitability as an
      alternative system for recombinant expression of parasitic nematode vaccine
      candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein,
      which is enriched in a gut membrane fraction capable of inducing significant
      protection against this important ovine gastrointestinal nematode. We show that
      H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass
      spectrometry identifies similar di- and tri-fucosylated structures to those on
      native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some
      glycan structural differences were observed, such as lack of LDNF. Serum antibody
      to native H11 binds to C. elegans recombinant H11 and most of the antibody to
      rH11 or native H11 is directed to glycan moieties. Despite these similarities, no
      reduction in worm burden or faecal egg count was observed following immunisation
      of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest
      that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to
      the protective effect of H11 and that additional components present in native H11
      enriched extract are likely required for enhancing the antibody response
      necessary for protection. 

PMID- 24289034
TI  - Fracture of the lateral femoral condyle.
AB  - The patient was a 25-year-old man who was currently enrolled in a military basic
      training program. He was evaluated by a physical therapist in a direct-access
      capacity for a chief complaint of right knee pain and swelling after his knee
      buckled and gave way during a training exercise on an obstacle course. The
      patient was evaluated by the physical therapist 2 days after his injury. Because
      the patient was unable to bear weight on his right lower extremity or flex his
      right knee to 90 degrees , the physical therapist ordered radiographs of the
      right knee, which demonstrated a fracture of the lateral femoral condyle
      posteriorly.

PMID- 24289035
TI  - December 2013 letter to the editor-in-chief.

PMID- 24289036
TI  - Response.

PMID- 24289038
TI  - Distribution of octenylsuccinic substituents in modified A and B polymorph starch
      granules.
AB  - The octenylsuccinic (OS) substituent distribution in octenylsuccinic anhydride
      (OSA)-modified normal maize and potato starches with different degrees of
      subsititution (DS) was studied using confocal laser scanning microscopy (CLSM)
      and surface gelatinization. The remaining non-gelatinized portions of starch
      granules after removal of surface-gelatinized starch (remaining granules) were
      studied with light microscopy, scanning electron microscopy, Fourier transform
      infrared spectroscopy (FTIR), and the level of succinylation. Results showed that
      greater proportions of the OS groups were present at the periphery than at the
      core of the granules. However, the granular interior of OS maize starch has
      higher fluorescent intensity than that of OS potato starch, as shown by CLSM. The
      DS of OS maize starch degraded less than that of OS potato starch under the same
      degree of gelatinization. In addition, the characteristic peaks of the remaining
      OS maize granules in the FTIR were more protruding than that of the OS potato
      granules after 50% chemical surface gelatinization. The results implied that
      maize starch displayed much more homogeneous OSA reaction pattern when compared
      to potato starch. With the special architectures (pinholes and channels) of
      maize, it is easier to change the location of OS groups than with potato starch
      by changing reaction conditions or starch pretreatments. 

PMID- 24289039
TI  - Coarse-grained model for colloidal protein interactions, B(22), and protein
      cluster formation.
AB  - Reversible protein cluster formation is an important initial step in the
      processes of native and non-native protein aggregation, but involves relatively
      long time and length scales for detailed atomistic simulations and extensive
      mapping of free energy landscapes. A coarse-grained (CG) model is presented to
      semiquantitatively characterize the thermodynamics and key configurations
      involved in the landscape for protein oligomerization, as well as experimental
      measures of interactions such as the osmotic second virial coefficient (B22).
      Based on earlier work (Gruenberger et al., J. Phys. Chem. B 2013, 117, 763), this
      CG model treats proteins as rigid bodies composed of one bead per amino acid,
      with each amino acid having specific parameters for its size, hydrophobicity, and
      charge. The net interactions are a combination of steric repulsions, short-range
      attractions, and screened long-range charge-charge interactions. Model
      parametrization was done by fitting simulation results against experimental value
      of B22 as a function of solution ionic strength for alpha-chymotrypsinogen A and
      gammaD-Crystallin (gD-Crys). The CG model is applied to characterize the pairwise
      interactions and dimerization of gD-Crys and the dependence on temperature,
      protein concentration, and ionic strength. The results illustrate that at
      experimentally relevant conditions where stable dimers do not form, the entropic
      contributions are predominant in the free-energy of protein cluster formation and
      colloidal protein interactions, arguing against interpretations that treat B22
      primarily from energetic considerations alone. Additionally, the results suggest
      that electrostatic interactions help to modulate the population of the different
      stable configurations for protein nearest-neighbor pairs, while short-range
      attractions determine the relative orientations of proteins within these
      configurations. Finally, simulation results are combined with Principal Component
      Analysis to identify those amino-acids/surface patches that form interprotein
      contacts at conditions that favor dimerization of gD-Crys. The resulting regions
      agree with previously found aggregation-prone sites, as well as suggesting new
      ones that may be important. 

PMID- 24289041
TI  - Infant atopic eczema and subsequent attention-deficit/hyperactivity disorder--a
      prospective birth cohort study.
AB  - BACKGROUND: Comorbidity between childhood atopic eczema (AE) and attention
      deficit/hyperactivity disorder (ADHD) has been observed, but temporal
      relationships remain unclear. METHODS: We analyzed data of a population-based,
      prospective birth cohort study among 770 children included at baseline in
      2000/2001 with follow-up up to age 11. Information on age at diagnosis of AE,
      rhinoconjunctivitis, and ADHD was obtained by questionnaires administered to
      parents and for AE also to caring physicians. Adjusted relative risks (aRR) with
      95% confidence intervals (95% CI) were modeled with a modified Poisson
      regression. RESULTS: Early AE up to age 4 yr was reported for 14.8% of the
      children by the parents and for 26.0% by the physicians with only fair agreement
      between these reports (kappa = 0.36). Based on parental reports, the association
      of early AE with early ADHD was strong (aRR: 5.17, 95% CI: 2.18; 12.28), but
      absent for late ADHD [aRR: 0.50 (0.13; 2.02)]. The association of late AE with
      late ADHD [aRR: 3.03 (0.75; 12.29)] was not statistically significant. This
      pattern was independent of the presence of rhinoconjunctivitis. CONCLUSIONS: The
      observed comorbidity between AE and ADHD may indicate vulnerability to develop
      ADHD symptoms in response to AE symptoms or through a common underlying
      mechanism. This vulnerability seems to decrease with time since AE onset and may
      be greater in early life. These temporal relationships should be considered in
      future research investigating mechanisms linking both diseases and in clinical
      efforts to screen for and prevent ADHD symptoms in children with AE.

PMID- 24289040
TI  - Hyperoxia increases the elastic modulus of alveolar epithelial cells through Rho
      kinase.
AB  - Patients with acute lung injury are administered high concentrations of oxygen
      during mechanical ventilation, and while both hyperoxia and mechanical
      ventilation are necessary, each can independently cause additional injury.
      However, the precise mechanisms that lead to injury are not well understood. We
      hypothesized that alveolar epithelial cells may be more susceptible to injury
      caused by mechanical ventilation because hyperoxia causes cells to be stiffer due
      to increased filamentous actin (f-actin) formation via the GTPase RhoA and its
      effecter Rho kinase (ROCK). We examined cytoskeletal structures in cultured
      murine lung alveolar epithelial cells (MLE-12) under normoxic and hyperoxic (48
      h) conditions. We also measured cell elasticity (E) using an atomic force
      microscope in the indenter mode. Hyperoxia caused increased f-actin stress fibers
      and bundle formation, an increase in g- and f-actin, an increase in nuclear area
      and a decrease in nuclear height, and cells became stiffer (higher E). Treatment
      with an inhibitor (Y-27632) of ROCK significantly decreased E and prevented the
      cytoskeletal changes, while it did not influence the nuclear height and area. Pre
      exposure of cells to hyperoxia promoted detachment when cells were subsequently
      stretched cyclically, but the ROCK inhibitor prevented this effect. Hyperoxia
      caused thickening of vinculin focal adhesion plaques, and inhibition of ROCK
      reduced the formation of distinct focal adhesion plaques. Phosphorylation of
      focal adhesion kinase was significantly reduced by both hyperoxia and treatment
      with Y-27632. Hyperoxia caused increased cell stiffness and promoted cell
      detachment during stretch. These effects were ameliorated by inhibition of ROCK.

PMID- 24289043
TI  - A novel TiO2 tape for fabricating dye-sensitized solar cells on universal
      conductive substrates.
AB  - The present paper describes a new method for manufacturing large scale, stable,
      transportable, and designable nanostructured porous TiO2 tapes on various
      substrates for use in photoelectrochemical cells. The method involves
      predeposition of TiO2 strips on the fluorine doped tin oxide (FTO) glass by
      screen-printing method, peeling off TiO2 strips from the substrate by a novel
      laser-assisted lift-off technique, sintering the formed TiO2 tapes at 500 
      degrees C for 15 min, and compressing the sintered TiO2 tapes on different
      conductive substrates with a low pressure rolling press to form mechanically
      stable, electrically conducting, porous nanostructured TiO2 electrodes at room
      temperature. Photoelectrochemical characteristics of the resulted electrodes are
      presented. Dye-sensitized solar cells (DSSCs) with the as-fabricated TiO2
      photoanodes on PET-ITO and FTO glass achieved a conversion efficiency of 4.2% and
      6.2%, respectively. The potential use of this new manufacturing method in future
      DSSC applications is discussed. 

PMID- 24289042
TI  - Infections in children with down syndrome and acute myeloid leukemia: a report
      from the Canadian infections in AML research group.
AB  - BACKGROUND: Children with Down syndrome (DS) are at high risk of infectious
      toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols
      optimized in children without DS. Our objective was to determine if children with
      DS and acute myeloid leukemia (AML) have a different risk of infection when
      treated with chemotherapy protocols developed for children with DS compared to
      AML treatment protocols developed for children without DS. METHODS: We conducted
      a retrospective, population-based cohort study that included DS children <= 18
      years of age with de novo, non-M3 AML diagnosed between January 1995 and December
      2004, and treated at 15 Canadian centers. Patients were monitored for infection
      from initiation of AML treatment until recovery from the last cycle of
      chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse,
      persistent disease or death (whichever occurred first). Trained research
      associates abstracted all information from each site. RESULTS: There were 31
      children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were
      treated according to a DS-specific protocol while 20 were treated with non-DS
      specific protocols. A total of 157 courses of chemotherapy were delivered.
      Microbiologically documented sterile site infection occurred in 11.9% and 14.3%
      of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was
      rare and there were no infection-related deaths. In multiple regression,
      treatment with a DS-specific protocol was independently associated with a
      reduction in microbiologically documented sterile site infection (adjusted odds
      ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and
      clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031)
      but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231). CONCLUSIONS:
      Our study suggests that children with DS do not experience excessive infectious
      toxicity during treatment for AML compared to children without DS. Incorporation
      of DS-specific AML treatment protocols is associated with a more favorable
      infection profile for children with DS-AML.

PMID- 24289044
TI  - Triple reuptake inhibitors: a patent review (2006 - 2012).
AB  - INTRODUCTION: The dysfunctions of three very important monoamine
      neurotransmitters, serotonin (5-HT), norepinephrine (NE) and dopamine (DA), are
      associated with some of important CNS diseases such as depression; developing the
      triple reuptake inhibitors (TRIs) that can rebalance 5-HT, NE and DA through the
      inhibition of the monoamine reuptake transporters will lead to a more effective
      and safer antidepressant. AREAS COVERED: This article reviews past 7 years'
      advances in the development of TRIs; a patent review (2006 - 2012), covering the
      discovery of new chemical entities, and development status of leading TRI
      clinical candidates. EXPERT OPINION: The development of TRIs has several
      challenges, including discovering a "single" agent that has the activities
      against all three monoamine reuptake transporters SERT, NET and DAT. More
      important is that the agent must have a "right ratio" to be safer and better
      tolerated for the treatment of depression. The TRIs can potentially be used for
      the treatment of other CNS diseases, such as pain, Parkinson's and attention
      deficit hyperactivity disorder (ADHD), depending on ratios of SERT, NET and DAT.

PMID- 24289045
TI  - Assessing responsiveness of health care services within a health insurance scheme
      in Nigeria: users' perspectives.
AB  - BACKGROUND: Responsiveness of health care services in low and middle income
      countries has been given little attention. Despite being introduced over a decade
      ago in many developing countries, national health insurance schemes have yet to
      be evaluated in terms of responsiveness of health care services. Although this
      responsiveness has been evaluated in many developed countries, it has rarely been
      done in developing countries. The concept of responsiveness is multi-dimensional
      and can be measured across various domains including prompt attention, dignity,
      communication, autonomy, choice of provider, quality of facilities,
      confidentiality and access to family support. This study examines the insured
      users' perspectives of their health care services' responsiveness. METHODS: This
      retrospective, cross-sectional survey took place between October 2010 and March
      2011. The study used a modified out-patient questionnaire from a responsiveness
      survey designed by the World Health Organization (WHO). Seven hundred and ninety
      six (796) enrolees, insured for more than one year in Kaduna State-Nigeria, were
      interviewed. Generalized ordered logistic regression was used to identify factors
      that influenced the users' perspectives on responsiveness to health services and
      quantify their effects. RESULTS: Communication (55.4%), dignity (54.1%), and
      quality of facilities (52.0%) were rated as "extremely important" responsiveness
      domains. Users were particularly contented with quality of facilities (42.8%),
      dignity (42.3%), and choice of provider (40.7%). Enrolees indicated lower
      contentment on all other domains. Type of facility, gender, referral, duration of
      enrolment, educational status, income level, and type of marital status were most
      related with responsiveness domains. CONCLUSIONS: Assessing the responsiveness of
      health care services within the NHIS is valuable in investigating the scheme's
      implementation. The domains of autonomy, communication and prompt attention were
      identified as priority areas for action to improve this responsiveness. For the
      Nigerian context, we suggest that health care providers in the NHIS should pay
      attention to these domains, and the associated characteristics of users, when
      delivering health care services to their clients. Policy makers, and the
      insurance regulatory agency, should consider the reform strategies of monitoring
      and quality assurance which focus on the domains of responsiveness to lessen the
      gap between users' expectations and their experiences with health services.

PMID- 24289046
TI  - Monitoring the rumen pectinolytic bacteria Treponema saccharophilum using real
      time PCR.
AB  - Treponema saccharophilum is a pectinolytic bacterium isolated from the bovine
      rumen. The abundance of this bacterium has not been well determined, reflecting
      the lack of a reliable and accurate detection method. To develop a rapid method
      for monitoring T. saccharophilum, we performed pyrosequencing of genomic DNA
      isolated from rumen microbiota to explore the 16S rRNA gene sequences of T.
      saccharophilum candidates. Species-specific primers were designed based on
      fifteen sequences of partial 16S rRNA genes generated through pyrosequencing with
      97% or higher similarity with T. saccharophilum DSM2985 along with sequence from
      type strain. The relative abundance of T. saccharophilum was quantified in both
      in vitro and in vivo rumen systems with varied pectin-containing forages using
      real-time PCR. There was a clear association of T. saccharophilum with alfalfa
      hay, which contains more pectin than Chinese wild rye hay or corn stover. The
      relative abundance of T. saccharophilum was as high as 0.58% in vivo, comparable
      with the population density of other common rumen bacteria. It is recognized that
      T. saccharophilum plays an important role in pectin digestion in the rumen. 

PMID- 24289048
TI  - Why the results of the American College of Surgeons Oncology Group Z0011 Trial
      are so important.

PMID- 24289047
TI  - Development and characterization of microsatellite markers for Morus spp. and
      assessment of their transferability to other closely related species.
AB  - BACKGROUND: Adoption of genomics based breeding has emerged as a promising
      approach for achieving comprehensive crop improvement. Such an approach is more
      relevant in the case of perennial species like mulberry. However, unavailability
      of genomic resources of co-dominant marker systems has been the major constraint
      for adopting molecular breeding to achieve genetic enhancement of Mulberry. The
      goal of this study was to develop and characterize a large number of locus
      specific genic and genomic SSR markers which can be effectively used for
      molecular characterization of mulberry species/genotypes. RESULT: We analyzed a
      total of 3485 DNA sequences including genomic and expressed sequences (ESTs) of
      mulberry (Morus alba L.) genome. We identified 358 sequences to develop
      appropriate microsatellite primer pairs representing 222 genomic and 136 EST
      regions. Primers amplifying locus specific regions of Dudia white (a genotype of
      Morus alba L), were identified and 137 genomic and 51 genic SSR markers were
      standardized. A two pronged strategy was adopted to assess the applicability of
      these SSR markers using mulberry species and genotypes along with a few closely
      related species belonging to the family Moraceae viz., Ficus, Fig and Jackfruit.
      While 100% of these markers amplified specific loci on the mulberry genome, 79%
      were transferable to other related species indicating the robustness of these
      markers and the potential they hold in analyzing the molecular and genetic
      diversity among mulberry germplasm as well as other related species. The inherent
      ability of these markers in detecting heterozygosity combined with a high average
      polymorphic information content (PIC) of 0.559 ranging between 0.076 and 0.943
      clearly demonstrates their potential as genomic resources in diversity analysis.
      The dissimilarity coefficient determined based on Neighbor joining method,
      revealed that the markers were successful in segregating the mulberry species,
      genotypes and other related species into distinct clusters. CONCLUSION: We report
      a total of 188 genomic and genic SSR markers in Morus alba L. A large proportion
      of these markers (164) were polymorphic both among mulberry species and
      genotypes. A substantial number of these markers (149) were also transferable to
      other related species like Ficus, Fig and Jackfruit. The extent of polymorphism
      revealed and the ability to detect heterozygosity among the cross pollinated
      mulberry species and genotypes render these markers an invaluable genomic
      resource that can be utilized in assessing molecular diversity as well as in QTL
      mapping and subsequently mulberry crop improvement through MAS.

PMID- 24289049
TI  - Medicine in small doses.

PMID- 24289051
TI  - Relevance of the American College of Surgeons Oncology Group Z0011 Trial to
      breast cancer in the Australian setting.
AB  - BACKGROUND: Conventional wisdom suggests that a patient with a positive sentinel
      node requires a completion axillary clearance to obtain full staging and durable
      regional control. However, this dictum has been challenged by the recent American
      College of Surgeons Oncology Group Z0011 Trial demonstrating that women with node
      positive breast cancer who underwent sentinel node biopsy only, and were treated
      with breast conserving surgery and radiation, had equivalent locoregional
      recurrence and survival rates to those who had a completion axillary clearance.
      The aim of our study was to determine what the clinical impact of the Z0011
      findings might be if patients were managed according to the Z0011 criteria in an
      Australian teaching hospital setting. METHODS: We performed a retrospective
      review, using prospectively collected data, of all female patients with breast
      cancer assessed at the Westmead Breast Cancer Institute in 2010 and identified
      the subgroup who would potentially have fulfilled all Z0011 criteria. The
      characteristics and management of this group were compared with node-positive and
      to mastectomy patient subgroups. RESULTS: A total of 280 patients with invasive
      breast cancer were identified. Twenty-six patients satisfied all Z0011 criteria,
      representing 9.3% of all patients and 21.5% of node-positive patients. Twenty-two
      (84.6%) patients had a subsequent axillary clearance, with six (27.3%) having
      additional positive nodes. CONCLUSIONS: The Z0011 study is relevant to 9.3% of
      all breast cancer patients and 21.5% of node-positive breast cancer patients
      treated in a major Australian teaching hospital.

PMID- 24289050
TI  - Paintings from the Cushing/Whitney Library of Yale University: the Eleventh
      Kenneth Fitzpatrick Russell Memorial Lecture - 2012.
AB  - In the early years of the introduction of Christianity into China, one American
      medical missionary distinguished himself by his kindness and generosity towards
      the Chinese people, and also by his surgical prowess. Peter Parker (1804-1888)
      was a graduate from the Yale University Medical School and was also an ordained
      minister. He came to the south China city of Canton (now called Guangzhou) in
      1834, built a hospital, treated the patients without charge and also groomed
      medical apprentices to help him in his work. He so impressed a Chinese artist,
      Lam Qua (1801-1860) that Lam offered to paint in oil, without charge, some of the
      unusual patients of Parker. Parker stayed in China until 1857. Altogether, there
      are about 109 paintings. More than 80 of them are in the Harvey Cushing/John Hay
      Whitney Medical Historical Library of the Yale University Medical School, New
      Haven, and 23 of them are in Guy's Hospital, London. A description of some of the
      paintings, together with accounts of Parker and Lam are discussed. 

PMID- 24289052
TI  - Mass lesions in right fifth toe in a dialysis patient: which surgery?

PMID- 24289053
TI  - Perineal small bowel evisceration following blunt abdominal trauma.

PMID- 24289054
TI  - 'Pantaloon' diaphragmatic hernia masquerading as a paraoesophageal hiatal hernia.

PMID- 24289055
TI  - Bouveret's syndrome: gastric outlet obstruction caused by a gallstone.

PMID- 24289056
TI  - Herpes reactivation after injection of dermal fillers.

PMID- 24289058
TI  - Trends in anemia management in US hemodialysis patients 2004-2010.
AB  - BACKGROUND: There have been major changes in the management of anemia in US
      hemodialysis patients in recent years. We sought to determine the influence of
      clinical trial results, safety regulations, and changes in reimbursement policy
      on practice. METHODS: We examined indicators of anemia management among incident
      and prevalent hemodialysis patients from a medium-sized dialysis provider over
      three time periods: (1) 2004 to 2006 (2) 2007 to 2009, and (3) 2010. Trends
      across the three time periods were compared using generalized estimating
      equations. RESULTS: Prior to 2007, the median proportion of patients with monthly
      hemoglobin >12 g/dL for patients on dialysis 0 to 3, 4 to 6 and 7 to 18 months,
      respectively, was 42%, 55% and 46% declined to 41%, 54%, and 40% after 2007, and
      declined more sharply in 2010 to 34%, 41%, and 30%. Median weekly Epoeitin alpha
      doses over the same periods were 18,000, 12,400, and 9,100 units before 2007;
      remained relatively unchanged from 2007 to 2009; and decreased sharply in the
      patients 3-6 and 6-18 months on dialysis to 10,200 and 7,800 units, respectively
      in 2010. Iron doses, serum ferritin, and transferrin saturation levels increased
      over time with more pronounced increases in 2010. CONCLUSION: Modest changes in
      anemia management occurred between 2007 and 2009, followed by more dramatic
      changes in 2010. Studies are needed to examine the effects of declining
      erythropoietin use and hemoglobin levels and increasing intravenous iron use on
      quality of life, transplantation rates, infection rates and survival.

PMID- 24289060
TI  - Fit in 50 years: participation in high school sports best predicts one's physical
      activity after age 70.
AB  - BACKGROUND: The health benefits of physical activity are widely established,
      including decreased risk for disease and improved mental well-being. Yet many
      children, adolescents, and adults do not meet the minimum recommendations
      specified in current public health guidelines and physical activity is known to
      decrease during the life course. The aim of this study was to identify background
      or personality characteristics that predict whether a healthy 25 year-old would
      become a physically active 75 year-old. This could have powerful implications for
      targeting physical activity and health interventions. METHOD: A unique data set
      was collected of 712 healthy United States males who passed a rigorous physical
      exam in the 1940s and who were surveyed 50 years later (in 2000). Their physical
      activity level after 50 years was correlated and regressed across a wide number
      of demographic, behavioral, and personality variables from when they were 50
      years younger. Data was analyzed in 2012. RESULTS: In contrast to prior beliefs,
      self-rated personality profile as a young man had little predictive influence on
      later-life physical activity. Instead, the single strongest predictor of later
      life physical activity was whether he played a varsity sport in high school, and
      this was also related to fewer self-reported visits to the doctor. CONCLUSION:
      Encouraging systematic or frequent physical activity at a young age - whether
      through school sports or club opportunities - might be the best investment in
      long-term activeness. This is relevant at a time when funding for many sports
      programs is being eliminated and play time is being replaced with screen time.

PMID- 24289061
TI  - Simulation training in obstetric practice.

PMID- 24289059
TI  - Protocol for the New Medicine Service Study: a randomized controlled trial and
      economic evaluation with qualitative appraisal comparing the effectiveness and
      cost effectiveness of the New Medicine Service in community pharmacies in
      England.
AB  - BACKGROUND: Medication non-adherence is considered an important cause of
      morbidity and mortality in primary care. This study aims to determine the
      effectiveness, cost effectiveness and acceptability of a complex intervention
      delivered by community pharmacists, the New Medicine Service (NMS), compared with
      current practice in reducing non-adherence to, and problems with, newly
      prescribed medicines for chronic conditions. METHODS/DESIGN: Research subject
      group: patients aged 14 years and above presenting in a community pharmacy for a
      newly prescribed medicine for asthma/chronic obstructive pulmonary disease
      (COPD); hypertension; type 2 diabetes or anticoagulant/antiplatelet agents in two
      geographical regions in England. DESIGN: parallel group patient-level pragmatic
      randomized controlled trial. INTERVENTIONS: patients randomized to either: (i)
      current practice; or (ii) NMS intervention comprising pharmacist-delivered
      support for a newly prescribed medicine. PRIMARY OUTCOMES: proportion of adherent
      patients at six, ten and 26 weeks from the date of presenting their prescriptions
      at the pharmacy; cost effectiveness of the intervention versus current practice
      at 10 weeks and 26 weeks; in-depth qualitative understanding of the
      operationalization of NMS in pharmacies. SECONDARY OUTCOMES: impact of NMS on:
      patients' understanding of their medicines, pharmacovigilance, interprofessional
      and patient-professional relationships and experiences of service users and
      stakeholders.Economic analysis: Trial-based economic analysis (cost per extra
      adherent patient) and long-term modeling of costs and health effects (cost per
      quality-adjusted-life-year) will be conducted from the perspective of National
      Health Service (NHS) England, comparing NMS with current practice.Qualitative
      analysis: a qualitative study of NMS implementation in different community
      settings, how organizational influences affect NMS delivery, patterns of NMS
      consultations and experiences of professionals and patients participating in NMS,
      and patients receiving current practice. SAMPLE SIZE: 250 patients in each
      treatment arm would provide at least 80% power (two-tailed alpha of 0.05) to
      demonstrate a reduction in patient-reported non-adherence from 20% to 10% in the
      NMS arm compared with current practice, assuming a 20% drop-out rate. DISCUSSION:
      At the time of submission of this article, 58 community pharmacies have been
      recruited and the interventions are being delivered. Analysis has not yet been
      undertaken. TRIAL REGISTRATION: Current controlled trials: ISRCTN23560818.
      Clinical Trials US (clinicaltrials.gov): NCT01635361.

PMID- 24289062
TI  - The conundrum of eclampsia and fitness to drive.
AB  - BACKGROUND: Australian Fitness to Drive guidelines suggest that anyone who has
      had a seizure of any kind in the context of a 'metabolic' disorder should avoid
      driving for a period of 6 months. The special case of eclampsia is not mentioned.
      AIMS: In this study, we aimed to assess what advice healthcare professionals
      involved in the peripartum care of women provide to women who have an eclamptic
      seizure, what investigations they would conduct to exclude other causes of
      seizures and their level of awareness of whether eclampsia was addressed in the
      Australian Fitness to Drive guidelines. MATERIALS AND METHODS: A survey of 165
      healthcare professionals attending the 2012 Society of Obstetric Medicine of
      Australia and New Zealand annual scientific meeting. Participants included
      registered nurses, midwives, consultant obstetricians, consultant physicians,
      doctors in training and others, interested in medical disorders of pregnancy.
      RESULTS: One hundred and nine conference attendees completed the survey (response
      rate 66.1%). 58 respondents (53.2%) had cared for 5 or more women with peripartum
      seizures, and 23 respondents (21.1%) had cared for 10 or more women with
      peripartum seizures. 46 respondents (42.2%) had never considered the issue of
      driving after an eclamptic seizure. For those who had considered the issue,
      advice ranged from no restriction (n = 5, 4.6%), no driving for 1-2 weeks (n =
      14, 12.8%), no driving for 3 months (n = 20, 18.4%) or no driving for 6 months (n
      = 6, 5.5%). CONCLUSIONS: Many healthcare professionals caring for women with
      peripartum seizures have not considered issues relating to fitness to drive after
      an eclamptic seizure. There is a wide range of advice provided. Better
      prospective data are required regarding the risk of subsequent seizure after
      eclampsia, to inform clear fitness to drive guidelines.

PMID- 24289063
TI  - Is colposcopy necessary at twelve months after large loop excision of the
      transformation zone? A clinical audit.
AB  - OBJECTIVE: The purpose of this study was to review outcomes from LLETZ (large
      loop excision of the transformation zone) procedures carried out for high-grade
      cervical intraepithelial neoplasia (CIN), in particular findings at colposcopy,
      cytology and HR-HPV(high-risk human papilloma virus) result to assess whether
      colposcopy provides any additional information in the management of women at 12
      months. METHODS: We retrospectively analysed 252 patients who had a LLETZ
      procedure for a HSIL (high-grade squamous intraepithelial lesion) between January
      2005 and December 2010. RESULTS: Eighty per cent of women who had a LLETZ
      procedure for HSIL were reviewed in our colposcopy clinic at 12 months after the
      procedure. Colposcopy at 12 months after LLETZ was documented as unsatisfactory
      for 30% of these women. The sensitivity of colposcopy at 12 months after LLETZ
      was 0.47, and the specificity was 0.95. CONCLUSION: Colposcopy examination is an
      insensitive tool for detection of persisting HPV-related change after excision of
      high-grade CIN. Its usefulness to investigate persistent or recurrent HSIL is
      further reduced by the high rate of unsatisfactory colposcopy examinations after
      a LLETZ procedure. Papanicolaou smear and HRHPV tests may be adequate follow-up
      at 12 months after LLETZ for women at low risk of recurrence of HSIL.

PMID- 24289064
TI  - Uterine necrosis after B-Lynch suture in a classical caesarean section.

PMID- 24289065
TI  - Re: Fasting blood glucose predicts response to extended-release metformin in
      gestational diabetes mellitus by Corbould A, Swinton F, Radford A, Campbell,
      McBeath S, Dennis A. Aust N Z J Obstet Gynaecol 2013; 53: 125-129.

PMID- 24289066
TI  - Re: Fasting blood glucose predicts response to extended-release metformin in
      gestational diabetes mellitus by Corbould A, Swinton F, Radford A, Campbell,
      McBeath S, Dennis A. Aust N Z J Obstet Gynaecol 2013; 53: 125-129.

PMID- 24289068
TI  - Cardiomyocyte culture - an update on the in vitro cardiovascular model and future
      challenges.
AB  - The success of any work with isolated cardiomyocytes depends on the
      reproducibility of cell isolation, because the cells do not divide. To date,
      there is no suitable in vitro model to study human adult cardiac cell biology.
      Although embryonic stem cells and induced pluripotent stem cells are able to
      differentiate into cardiomyocytes in vitro, the efficiency of this process is
      low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac
      surgical waste or, alternatively, from fetal heart tissue is another option.
      However, to overcome various issues related to human tissue usage, especially
      ethical concerns, researchers use large- and small-animal models to study cardiac
      pathophysiology. A simple model to study the changes at the cellular level is
      cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have
      their own advantages and drawbacks, alternative strategies have been developed in
      the last two decades to minimise animal usage and interspecies differences. This
      review discusses the use of freshly isolated murine cardiomyocytes and
      cardiomyocyte alternatives for use in cardiac disease models and other related
      studies. 

PMID- 24289069
TI  - Assessment of arterial stiffness using applanation tonometry.
AB  - Augmentation index (AIx) and pulse wave velocity (PWV) assess functional and
      structural aspects of the vascular wall and are independent markers of
      cardiovascular morbidity and mortality. Like blood pressure, many factors,
      genetic, structural, and physiological, affect AIx and PWV. AIx and PWV can be
      assessed noninvasively using applanation tonometry. The technique is simple, but
      comes with a number of practical and technical limitations that have not been
      well documented and (or) explored. This review considers pulse wave analysis in
      the context of cardiovascular disease, and considers its limitations. Data are
      presented indicating that the placement of the probe is critical, and that the
      amplitude of the obtained signal is related to the variability in measurements.
      On a more theoretical note, issues are discussed regarding the applied transfer
      functions that are built in the devices to assess central AIx from peripheral
      waveforms. Altogether, PWV and its analysis are useful additions to the arsenal
      of parameters that can be used to assess vascular health and to estimate vascular
      risk. Yet, our analysis underscores the necessity for precise operating
      procedures, and calls for transparency regarding the applied transfer functions
      of commercial devices. 

PMID- 24289070
TI  - Co-agonist of glucagon and GLP-1 reduces cholesterol and improves insulin
      sensitivity independent of its effect on appetite and body weight in diet-induced
      obese C57 mice.
AB  - Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors reduce
      body weight without inducing hyperglycemia in rodents. However, the effect of a
      co-agonist on insulin sensitivity and lipid metabolism has not been thoroughly
      assessed. Diet-induced obese (DIO) mice received 0.5 mg.kg(-1) of co-agonist or
      2.5 mg.kg(-1) of glucagon or 8 MUg.kg(-1) of exendin-4 by subcutaneous route,
      twice daily, for 28 days. A separate group of mice was pair-fed to the co-agonist
      treated group for 28 days. Co-agonist treatment reduced food intake and reduced
      body weight up to 28 days. In addition, it reduced leptin levels and increased
      fibroblast growth factor 21 (FGF21) levels in plasma, when compared with control
      and pair-fed groups. Co-agonist treatment decreased triglyceride levels in serum
      and liver and reduced serum cholesterol, mainly due to reduction in low-density
      lipoprotein (LDL) cholesterol. These changes were not seen with pair-fed
      controls. Co-agonist treatment improved glucose tolerance and increased insulin
      sensitivity, as observed during glucose and insulin-tolerance test,
      hyperinsulinemic clamp, and reduced gluconeogenesis, as observed in pyruvate
      tolerance test. The effects on insulin sensitivity and lipid levels are mostly
      independent of the food intake or body weight lowering effect of the co-agonist. 

PMID- 24289071
TI  - Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in
      vitro and in vivo.
AB  - Geraniin has previously been reported to possess extensive biological activity.
      In this study, we reported that geraniin is an inhibitor of tumor activity in
      vitro and in vivo. Geraniin suppressed the proliferation of A549 cells in a dose-
      and time-dependent manner. Geraniin arrested the cell cycle in the S phase and
      induced a significant accumulation of reactive oxygen species (ROS), as well as
      an increased percentage of cells with mitochondrial membrane potential (MMP)
      disruption. Western blot analysis showed that geraniin inhibited Bcl-2 expression
      and induced Bax expression to disintegrate the outer mitochondrial membrane and
      cause cytochrome c release. Mitochondrial cytochrome c release was associated
      with the activation of caspase-9 and caspase-3 cascades. Additionally, geraniin
      resulted in tumor growth inhibition in A549 xenografts. Our results indicate
      cytotoxic activity of geraniin towards cancer cells in vitro and in vivo. 

PMID- 24289072
TI  - Prolonged AMP-activated protein kinase induction impairs vascular functions.
AB  - AMP-activated protein kinase (AMPK) is a regulator of cellular metabolism and is
      involved in the pathogenesis of several diseases, including type 2 diabetes and
      cardiovascular diseases. Data showing the effects of AMPK on vasculature are
      controversial. Therefore, the aim of this study was to determine the impact of
      prolonged AMPK activation on vascular functions. For this purpose we have
      examined the role of AMPK in endothelium-dependent and -independent relaxation
      and vascular contractions. For this, we incubated thoracic aortic rings, from
      rats, with AMPK activator 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside
      (AICAR, 500 MUmol/L or 2 mmol/L) in the presence or absence of AMPK inhibitor
      compound C (10 MUmol/L). Next, cumulative dose-response curves to acetylcholine
      (ACh) (10(-9)-10(-4) mol/L), nitroglycerine (NG) (10(-9)-3 * 10(-5) mol/L), and
      noradrenaline (NA) (10(-9)-10(-4) mol/L) were obtained. Endothelial nitric oxide
      synthase (eNOS) protein expression was determined. Our results show that
      endothelium-dependent relaxation was inhibited after AICAR treatment, and that
      this effect was reversed by AMPK inhibition. Moreover, AICAR enhanced the
      contractile response to NA and caused a decrease in eNOS protein expression. In
      conclusion, prolonged AMPK induction causes endothelial impairment, possibly via
      increased degradation and (or) reduced expression of eNOS. 

PMID- 24289073
TI  - Intraluminal hyperglycaemia causes conduit and resistance artery dilatation and
      inhibits vascular autoregulation in the anaesthetised pig.
AB  - The effect of intraluminal hyperglycaemia was investigated in the iliac artery of
      11 anaesthetised pigs. Following isolation of a test segment, hyperglycaemic
      blood (40 mmol.L(-1)) caused a significant dilatation of the artery of 167 +/-
      208 MUm (mean +/- SD; n = 6, P = 0.031). Dilatations were reduced by N(G)-nitro-l
      arginine methyl esther (250 MUg.mL(-1)) from 145 +/- 199 to 38 +/- 5 MUm), but
      this was not statistically significant (n = 6, P = 0.18). Intra-arterial
      infusions of d-glucose (20-40 mmol.L(-1).min(-1)), during graded constrictions,
      caused statistically significant increases in blood flow (n = 11, P = 0.0013).
      Vasodilatation was confirmed by measurements of the ratio of immediate pressure
      steps to flow steps (?P/?F) during the graded obstruction experiments, showing a
      decrease in instantaneous vascular resistance from a control of 0.62 +/- 0.30 to
      0.33 +/- 0.34 mm Hg.mL(-1).min(-1) (n = 7, P = 0.016). Autoregulation was
      assessed from the slopes of the plots of steady-state flow versus pressure. There
      were significant increases in the slope from 2.32 +/- 1.03 to 5.88 +/- 5.60
      mL.min(-1).(mm Hg)(-1) (n = 7, P = 0.0078), indicating significant impairment of
      autoregulation. In conclusion, luminal hyperglycaemia relaxes both arterial and
      resistance vessel smooth muscle. 

PMID- 24289074
TI  - Protective functions of peroxiredoxin-1 against cytokine-induced MIN6 pancreatic
      beta-cell line death.
AB  - Pancreatic beta-cells play a crucial role in glucose homeostasis, and the failure
      of these cells to function results in the development of type 1 diabetes (T1D).
      The MIN6 cell line, which closely resembles pancreatic beta-cells, was used to
      unravel the relationship between pancreatic beta-cell function and the
      antioxidant enzyme PRX-1. PRX-1 was knocked down in MIN6 cells using a shPRX-1
      lentiviral construct, and a mixture of inflammatory cytokines was administered to
      challenge the MIN6 cells. Nitric oxide (NO) production and inducible NO synthase
      (iNOS) expression were elevated in shPRX-1 compared with the control. Also, shPRX
      1 transduced cells showed higher levels of NF-kappaB nuclear translocation,
      suggesting that PRX-1 has a regulatory role in NF-kappaB nuclear translocation
      and iNOS expression. In correlation with NO levels, decreased anti-apoptotic gene
      Bcl-xl level and elevated pro-apoptotic gene Bim levels were observed in shPRX-1
      cells compared with scramble, and cell viability decreased accordingly. A rescue
      experiment was performed subsequently using an iNOS inhibitor to confirm NO as
      the cause of cell death. Overall, the results of this study suggest possible
      protective roles of the antioxidant enzyme PRX-1 in the insulinoma cell line MIN6
      and possibly in pancreatic beta-cells under T1D conditions. 

PMID- 24289075
TI  - Resveratrol attenuates left ventricular remodeling in old rats with COPD induced
      by cigarette smoke exposure and LPS instillation.
AB  - The objective of this study was to investigate left cardiac damage and the
      cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old
      were divided into three groups: control (CTL), smoking and lipopolysaccharides
      (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology,
      oxidative stress, and apoptosis index were measured. Expression of myocardial
      SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and
      Western blot detection. The heart weight-body weight ratio (LVW/BW) increased in
      the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of
      fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS
      group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group,
      which could be inhibited by resveratrol. Resveratrol significantly increased the
      activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde
      (MDA) level in the SM/LPS-Res group. There was a significant decrease in the
      extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the
      SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the
      SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and
      left ventricular remodeling and enhanced the decreased expression of SIRT1 in
      hearts of old rats with emphysema and thus might be a therapeutic modality for
      cardiac injury complicated in chronic obstructive pulmonary disease (COPD).

PMID- 24289076
TI  - Modulation of thioacetamide-induced liver fibrosis/cirrhosis by sildenafil
      treatment.
AB  - Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment
      of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it
      promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis
      has long been speculated, where the 2 are believed to progress together. In this
      study, the ability of sildenafil (10 mg.(kg body mass)(-1), orally, once daily)
      to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by
      thioacetamide injection (200 mg.kg(-1), intraperitoneal (i.p.), 3 times.week(-1))
      in male Sprague-Dawley rats has been investigated. Sildenafil administration,
      either to prevent or to reverse liver fibrosis/cirrhosis significantly improved
      the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn,
      hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic
      mediator transforming growth factor beta1. In co-ordination with such
      improvement, fibrosis grades declined and fibrosis retracted. Herein, the
      observed results provide evidence for the potential therapeutic efficacy of
      sildenafil as an antifibrotic agent. 

PMID- 24289077
TI  - Vinpocetine protects liver against ischemia-reperfusion injury.
AB  - Hepatic ischemia-reperfusion (IR) injury is a clinical problem that leads to
      cellular damage and organ dysfunction mediated mainly via production of reactive
      oxygen species and inflammatory cytokines. Vinpocetine has long been used in
      cerebrovascular disorders. This study aimed to explore the protective effect of
      vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping
      the common hepatic artery and portal vein for 30 min followed by 30 min of
      reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH)
      activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver
      histopathology were assessed. IR resulted in marked histopathology changes in
      liver tissues coupled with elevations in serum transaminases and liver LDH
      activities. IR also increased the production of liver lipid peroxides, nitric
      oxide, and inflammatory cytokines interleukin-1beta and interleukin-6, in
      parallel with a reduction in reduced glutathione and interleukin-10 in the liver.
      Pretreatment with vinpocetine protected against liver IR-induced injury, in a
      dose-dependent manner, as evidenced by the attenuation of oxidative stress as
      well as inflammatory and liver injury biomarkers. The effects of vinpocetine were
      comparable with that of curcumin, a natural antioxidant, and could be attributed
      to its antioxidant and anti-inflammatory properties. 

PMID- 24289078
TI  - Modulation of arginine and asymmetric dimethylarginine concentrations in liver
      and plasma by exogenous hydrogen sulfide in LPS-induced endotoxemia.
AB  - Plasma levels of asymmetric dimethylarginine (ADMA) are known to be elevated
      under pathological conditions, but reports on intracellular ADMA levels are
      scarce. In this study, we investigated whether lipopolysaccharide (LPS)-induced
      endotoxemia alters the intra- and extra-cellular partition of l-arginine and
      ADMA. The effect of H2S pretreatment was also researched. Wistar rats were given
      sodium hydrogen sulfide (NaHS, 1 mg.(kg body mass)(-1)) one hour before the LPS
      injections (20 mg.kg(-1)). Six hours after the LPS treatment, the animals were
      sacrificed. Myeloperoxidase (MPO) and dimethylarginine dimethylaminohydrolase
      (DDAH) activities and levels of hypoxia-inducible factor (HIF)-1alpha were
      measured in the liver. ADMA and arginine levels were determined using HPLC. LPS
      injection caused liver injury, as evidenced by the activities of alanine
      transaminase, aspartate transaminase, and arginase. LPS increased l-arginine
      content and decreased DDAH activity in the rat liver. MPO activity and HIF-1alpha
      levels indicated inflammation and hypoxia. Despite the accumulation of ADMA in
      the plasma, the level remained unchanged in the liver. NaHS pretreatment restored
      both the DDAH activity and intracellular l-arginine levels. It is concluded that
      increased H2S generation has a potency to restore hepatic l-arginine levels and
      ADMA handling in endotoxemia. Extra- and intra-cellular partitions of ADMA seem
      to depend on transport proteins as well as the DDAH activity. 

PMID- 24289079
TI  - Grape seed and skin extract mitigates heart and liver oxidative damage induced by
      a high-fat diet in the rat: gender dependency.
AB  - Obesity is a public health problem contributing to morbidity and mortality from
      metabolic syndrome. It has long been recognized that there is a gender dependency
      in several obesity-related health risks. Using a high fat diet (HFD) to induce
      obesity in Wistar rats, we studied the gender dependency of fat-induced oxidative
      stress in the heart and liver, with a special emphasis on the distribution of
      transition metals, as well as the protective effects of grape seed and skin
      extract (GSSE). HFD induced obesity in both male and female rats, characterized
      by increased body weight as well as relative liver mass in both genders, and
      increased relative heart mass in the males only. HFD also provoked the
      accumulation of triglycerides and total cholesterol into the male hearts, and
      into the livers of both genders. HFD induced oxidative stress in the male hearts
      and also in the livers of both genders. Furthermore, HFD affected cardiac levels
      of copper in the males, and hepatic levels of copper and zinc in both genders,
      whereas HFD affected free iron in the male hearts and female livers,
      specifically. In conclusion, HFD treatment altered transition metal homeostasis
      more drastically in the male heart than in the female liver, and GSSE efficiently
      protected these organs against fat-induced disturbances, regardless of gender. 

PMID- 24289080
TI  - Local insulin application on the carotid artery inhibits neointima formation.
AB  - Anti-mitogenic agents currently used to prevent restenosis in drug-eluting stents
      delay re-endothelialization. Delayed re-endothelialization is now considered as
      the main cause of late stent thrombosis with drug-eluting stents, which
      emphasizes the need for new treatments. We have shown that systemic insulin
      treatment decreases neointimal growth and accelerates re-endothelialization after
      arterial injury in a rat model of restenosis. However, systemic insulin treatment
      cannot be given to non-diabetic individuals because of the risk of hypoglycemia.
      Thus, we investigated whether local insulin treatment is also effective in
      reducing neointimal growth after arterial injury. Rats were given local vehicle
      or local insulin delivered via Pluronic gel applied around the carotid artery
      immediately following balloon injury. Plasma glucose and systemic insulin levels
      were not affected by local insulin treatment. Insulin decreased intimal area at
      28 days (P < 0.05) and also inhibited vascular smooth muscle cell migration by
      60% at 4 days (P < 0.05). NPH (a longer-lasting insulin) also decreased
      neointimal area. These results indicate that local insulin treatment can lead to
      decreased restenosis, suggesting a protective vascular effect of insulin in vivo
      and that local insulin treatment, possibly via insulin-eluting stents, may be
      clinically relevant. 

PMID- 24289081
TI  - Calcium paradox induces apoptosis in the isolated perfused Rana ridibunda heart:
      involvement of p38-MAPK and calpain.
AB  - "Calcium paradox" as a term describes the deleterious effects conferred to a
      heart perfused with a calcium-free solution followed by repletion, including loss
      of mechanical activity and sarcomere disruption. Given that the signaling
      mechanisms triggered by calcium paradox remain elusive, in the present study, we
      tried to investigate them in the isolated perfused heart from Rana ridibunda.
      Calcium paradox was found to markedly activate members of the MAPKs (p43-ERK,
      JNKs, p38-MAPK). In addition to lactate dehydrogenase (LDH) release in the
      perfusate (indicative of necrosis), we also confirmed the occurrence of apoptosis
      by using the TUNEL assay and identifying poly(ADP-ribose) polymerase (PARP)
      fragmentation and upregulated Bax expression. Furthermore, using MDL28170 (a
      selective calpain inhibitor), a role for this protease was revealed. In addition,
      various divalent cations were shown to exert a protective effect against the
      calcium paradox. Interestingly, SB203580, a p38-MAPK inhibitor, alleviated
      calcium-paradox-conferred apoptosis. This result indicates that p38-MAPK plays a
      pro-apoptotic role, contributing to the resulting myocardial dysfunction and cell
      death. To our knowledge, this is the first time that the calcium paradox has been
      shown to induce apoptosis in amphibians, with p38-MAPK and calpain playing
      significant roles. 

PMID- 24289082
TI  - Impaired chemoreflex sensitivity during septic shock induced by cecal ligation
      and perforation.
AB  - In this study, we sought to determine the effects produced by cecal ligation and
      perforation (CLP) on the autonomic responses to the activation of peripheral
      chemoreflexes in conscious rats. The peripheral chemoreflex was activated with
      potassium cyanide (KCN; 40 MUg.(0.1 mL)(-1); intravenous injection (i.v.)) in
      male Wistar rats 3, 6, 12, and 24 h after CLP or sham surgery. The mean arterial
      pressure (MAP), heart rate (HR), and respiratory frequency (fR) were recorded
      simultaneously. CLP surgery reduced the baseline MAP when compared with the sham
      animals. In the animals of the sham group, the autonomic responses to KCN
      produced increases in MAP and fR as well as a decrease in HR. However, 12 and 24
      h after CLP surgery, the autonomic responses to KCN were attenuated. The
      restoration of MAP by i.v. injected l-NAME or phenylephrine did not restore the
      autonomic response to KCN in rats subjected to CLP. These data show that septic
      shock induced by CLP compromised the autonomic responses to peripheral
      chemoreflex activation in conscious rats, suggesting that an important regulatory
      mechanism is impaired during the course of this condition. 

PMID- 24289083
TI  - Blockage of hERG current and the disruption of trafficking as induced by
      roxithromycin.
AB  - Roxithromycin is an oral macrolide antibiotic agent that has been repeatedly
      reported to provoke excessive prolongation of the Q-T interval and torsades de
      pointes in clinical settings. To investigate the mechanisms underlying the
      arrhythmogenic side effects of roxithromycin, we studied the molecular mechanisms
      of roxithromycin on human ether-a-go-go-related gene (hERG) K(+) channels
      expressed in human embryonic kidney (HEK293) cells. Roxithromycin was found to
      inhibit wild-type (WT) hERG currents in a concentration-dependent manner with a
      half-maximum block concentration (IC50) of 55.8 +/- 9.1 MUmol/L. S6 residue hERG
      mutants (Y652A and F656C) showed reduced levels of hERG current blockage
      attributable to roxithromycin. Roxithromycin also inhibited the trafficking of
      hERG protein to the cell membrane, as confirmed by Western blot analysis and
      confocal microscopy. These findings indicate that roxithromycin may cause
      acquired long-QT syndrome via direct inhibition of hERG current and by disruption
      of hERG protein trafficking. Mutations in drug-binding sites (Y652A or F656C) of
      the hERG channel were found to attenuate hERG current blockage by roxithromycin,
      but did not significantly alter the disruption of trafficking. 

PMID- 24289084
TI  - Atypical antipsychotics such as risperidone, but not paliperidone, worsen
      vascular endothelial function via upregulation of adhesion molecules VCAM-1, ICAM
      1, and E-selectin in diabetic rats.
AB  - Schizophrenia doubles the odds of diabetes, and atypical antipsychotics (AAPs)
      also increase risk of diabetes. Indeed, little is known about the effects of AAPs
      on vascular dysfunctions associated with diabetes. This study aimed to determine
      the effects of risperidone (RISP) and paliperidone (PALI) on the vascular
      function of diabetic rats. Diabetes was induced by feeding with a high-fat diet
      followed by the administration of streptozotocin (35 mg.(kg body mass)(-1), by
      intraperitoneal injection). Rats received RISP or PALI (1.25 mg.kg(-1).d(-1), per
      os) for 3 weeks. Endothelium-dependent relaxation, systolic blood pressure, lipid
      profile, insulin resistance, and adhesion molecules, vascular cell-adhesion
      molecule-1 (VCAM-1), intracellular-adhesion-molecule-1 (ICAM-1), and E-selectin
      were investigated. RISP significantly worsened the impaired endothelium-dependent
      relaxation of diabetic aortic rings with upregulation of the adhesion molecules
      VCAM-1, ICAM-1, and E-selectin, and proinflammatory cytokines MPC-1 and TNF
      alpha. RISP augmented the metabolic dysfunctions and reduced insulin sensitivity
      in the insulin tolerance test as well as HOMA-IR. PALI produced insignificant
      effects on vascular and metabolic aberrations. Our results suggest that RISP, but
      not PALI, aggravates the metabolic abnormalities and vascular dysfunction
      associated with diabetes, which may be mediated by upregulation of VCAM-1, ICAM
      1, and E-selectin. Nevertheless, future investigation for the possible mechanisms
      underlying the difference noticed between the 2 AAPs is warranted. 

PMID- 24289085
TI  - Cluster of erythrocyte band 3: a potential molecular target of exhaustive
      exercise-induced dysfunction of erythrocyte deformability.
AB  - The aim of this study is to explore the effect of exhaustive exercise on
      erythrocyte band 3 (SLC4A1; EB3). The association between the alterations of EB3
      and red blood cell (RBC) deformability induced by exercise-induced dysfunction
      has been investigated. Rats were divided among 2 groups: (i) control (C), and
      (ii) exercise exhausted (E). RBC deformability was investigated in the rats in
      the exhaustive exercise and control groups. Erythrocytes from the control and
      exercise-exhausted groups were evaluated for the expression of erythrocyte band 3
      through immunoblotting and immunofluorescence studies. Exhaustive exercise led to
      significant increments in the levels of clustering of erythrocyte band 3 along
      with the conjugation of membrane proteins to form high-molecular-weight complexes
      (P < 0.05). Under shear stresses, RBC deformability was found to decline
      significantly in the exhaustive exercise groups compared with the control group.
      These data suggest that the RBC dysfunction observed during exercise-induced
      oxidative stress could be associated with alterations in the structure and
      function of erythrocyte band 3, which in turn leads to dysfunction in the
      rheological properties of RBCs. These results provide further insight into
      erythrocyte damage induced by exhaustive exercise. 

PMID- 24289086
TI  - Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice.
AB  - Early growth response-1 one gene (Egr-1), one of the immediate early response
      genes, plays an important role in the adaptive response of the myocardium to
      hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on
      cardiac function. Egr-1 knock-out (Egr-1(-/-)) homozygous mice were employed to
      evaluate the electrophysiological and molecular properties of left ventricular
      cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium
      measurements, real-time PCR, and Western blot. Action potential was prolonged and
      diastolic potential was positive-shifted in VCMs isolated from Egr-1(-/-) mice,
      in comparison with those from their wild-type (WT) littermates. The calcium
      content of the sarcoplasmic reticulum was reduced and the decay time for steady
      state calcium transient slowed down. Serca2, Ryr, L-type Ca(2+)-channel, and PLB
      mRNA expression were reduced in Egr-1(-/-) mice compared with the controls.
      Moreover, Serca2 protein was reduced, while the amount of Ncx1 protein was
      increased in Egr-1(-/-) hearts compared with those of the WT littermates.
      Furthermore, genes involved in heart development (GATA-4, TGF-beta) and in Egr-1
      regulation (Nab1, Nab2) were down regulated in Egr-1(-/-) mice. These results
      suggest that Egr-1 plays a pivotal role in regulating excitation-contraction
      coupling in cardiac myocytes. 

PMID- 24289087
TI  - Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374,
      and determination of its possible mechanisms.
AB  - This study was carried out to determine the antinociceptive activity of a novel
      synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl
      5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of
      the opioid, vanilloid, glutamate, and nitric oxide - cyclic guanosine
      monophosphate (NO/cGMP) systems in modulating the observed antinociception.
      ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally
      to mice 60 mins prior to exposure to various antinociceptive assays. From the
      results obtained, ASH21374 exhibited significant (P < 0.05) antinociceptive
      activity in the abdominal constriction, hot-plate, and formalin tests that was
      comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively.
      ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre
      treatment with 5 mg/kg naloxone significantly (P < 0.05) inhibited the activity
      in all assays, while pretreatment with 10 mg/kg beta-funaltraxamine, 1 mg/kg
      naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P < 0.05) reversed the
      activity in the abdominal constriction test. l-Arginine, N(G)-nitro-l-arginine
      methyl esters (l-NAME), methylene blue, and their combinations, failed to inhibit
      the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated
      antinociceptive activities on the peripheral and central nervous systems,
      mediated through the activation of opioid receptors, inhibition of the
      glutamatergic system, and attenuation of vanilloid-mediated nociceptive
      transmission. Further studies have been planned to determine the pharmacological
      potential of ASH21374. 

PMID- 24289088
TI  - Loss of hepatic aryl hydrocarbon receptor protein in adrenalectomized rats does
      not involve altered levels of the receptor's cytoplasmic chaperones.
AB  - The aryl hydrocarbon receptor (AHR) plays physiological roles and mediates
      adaptive and toxic responses to environmental pollutants. Adrenalectomized rats
      display decreased hepatic AHR protein levels, with no change in mRNA, and
      selectively impaired induction of cytochrome P450 1B1. This is similar to
      reported phenotypes for mice with hepatocyte-specific conditional deletion of AHR
      interacting protein (AIP), a chaperone protein of the cytoplasmic AHR complex. In
      this study, we demonstrated that adrenalectomy (ADX) and acute dexamethasone
      (DEX) treatment do not alter hepatic AIP mRNA or protein levels. Also, hepatic
      protein levels of the 90 kDa heat shock protein and p23 were not altered by ADX
      or acute DEX treatment. These results suggest that the loss of rat hepatic AHR
      protein following ADX cannot be explained by changes in the levels of the
      receptor's cytoplasmic chaperone proteins. 

PMID- 24289090
TI  - The eye contact effect in request and emblematic hand gestures.
AB  - Request and emblematic gestures, despite being both communicative gestures, do
      differ in terms of social valence. Indeed, only the former are used to
      initiate/maintain/terminate an actual interaction. If such a difference is at
      stake, a relevant social cue, i.e. eye contact, should have different impacts on
      the neuronal underpinnings of the two types of gesture. We measured blood oxygen
      level-dependent signals, using functional magnetic resonance imaging, while
      participants watched videos of an actor, either blindfolded or not, performing
      emblems, request gestures, or meaningless control movements. A left-lateralized
      network was more activated by both types of communicative gestures than by
      meaningless movements, regardless of the accessibility of the actor's eyes.
      Strikingly, when eye contact was taken into account as a factor, a right
      lateralized network was more strongly activated by emblematic gestures performed
      by the non-blindfolded actor than by those performed by the blindfolded actor.
      Such modulation possibly reflects the integration of information conveyed by the
      eyes with the representation of emblems. Conversely, a wider right-lateralized
      network was more strongly activated by request gestures performed by the
      blindfolded than by those performed by the non-blindfolded actor. This probably
      reflects the effect of the conflict between the observed action and its
      associated contextual information, in which relevant social cues are missing. 

PMID- 24289089
TI  - Th17 cells favor inflammatory responses while inhibiting type I collagen
      deposition by dermal fibroblasts: differential effects in healthy and systemic
      sclerosis fibroblasts.
AB  - INTRODUCTION: T helper (Th)-17 cells are increased in systemic sclerosis (SSc).
      We therefore assessed whether Th17 cells could modulate the inflammatory and
      fibrotic responses in dermal fibroblasts from healthy donors (HD) and SSc
      individuals. METHODS: Fibroblasts were obtained from 14 SSc and 8 HD skin
      biopsies. Th17 clones were generated from healthy peripheral blood upon
      enrichment of CC chemokine receptor (CCR)-4/CCR6/CD161 expressing cells. Their
      cytokine production was assessed by flow cytometry and multiplex beads
      immunoassay. Fibroblast production of monocyte chemoattractant protein (MCP)-1,
      interleukin (IL)-8, matrix metalloproteinase (MMP)-1, tissue inhibitor of
      metalloproteinase (TIMP)-1, MMP-2 and type-I collagen was quantified by enzyme
      linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), and changes in
      their transcription levels assessed by real-time PCR. Intracellular signals were
      dissected by western blot and the use of pharmacological inhibitors. IL-17A,
      tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) blocking reagents
      were used to assess the specificity of the observed effects. RESULTS: IL-17A
      increased MCP-1, IL-8 and MMP-1 production in a dose-dependent manner while
      having no effect on type I collagen in HD and SSc fibroblasts both at protein and
      mRNA levels. Nuclear factor-kappa B (NF-kappaB) and p38 were preferentially
      involved in the induction of MCP-1 and IL-8, while MMP-1 was most dependent on c
      Jun N-terminal kinase (JNK). Supernatants of activated Th17 clones largely
      enhanced MCP-1, IL-8 and MMP-1 while strongly inhibiting collagen production. Of
      note, the production of MCP-1 and IL-8 was higher, while collagen inhibition was
      lower in SSc compared to HD fibroblasts. The Th17 clone supernatant effects were
      mostly dependent on additive/synergistic activities between IL-17A, TNF and in
      part IFN-gamma. Importantly, the inhibition of type I collagen production induced
      by the Th17 clone supernatants was completely abrogated by blockade of IL-17A,
      TNF and IFN-gamma mostly in SSc fibroblasts, revealing an intrinsic resistance to
      inhibitory signals in SSc. CONCLUSIONS: Our findings demonstrate that in vitro
      Th17 cells elicit pro-inflammatory responses while restraining collagen
      production. Thus, the increased Th17 cell number observed in SSc may impact on
      the inflammatory component of the disease simultaneously potentially providing a
      protective role against fibrosis.

PMID- 24289091
TI  - Classical cardiovascular disease risk factors associate with vascular function
      and morphology in rheumatoid arthritis: a six-year prospective study.
AB  - INTRODUCTION: Patients with rheumatoid arthritis (RA) are at an increased risk
      for cardiovascular disease (CVD). An early manifestation of CVD is endothelial
      dysfunction which can lead to functional and morphological vascular
      abnormalities. Classical CVD risk factors and inflammation are both implicated in
      causing endothelial dysfunction in RA. The objective of the present study was to
      examine the effect of baseline inflammation, cumulative inflammation, and
      classical CVD risk factors on the vasculature following a six-year follow-up
      period. METHODS: A total of 201 RA patients (155 females, median age (25th to
      75th percentile): 61 years (53 to 67)) were examined at baseline (2006) for
      presence of classical CVD risk factors and determination of inflammation using C
      reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up
      (2012) patients underwent assessments of microvascular and macrovascular
      endothelium-dependent and endothelium-independent function, along with assessment
      of carotid atherosclerosis. The CRP and ESR were recorded from the baseline study
      visit to the follow-up visit for each patient to calculate cumulative
      inflammatory burden. RESULTS: Classical CVD risk factors, but not RA disease
      related inflammation, predicted microvascular endothelium-dependent and
      endothelium-independent function, macrovascular endothelium-independent function
      and carotid atherosclerosis. These findings were similar in a sub-group of
      patients free from CVD, and not receiving non-steroidal anti-inflammatory drugs,
      cyclooxygenase 2 inhibitors or biologics. Cumulative inflammation was not
      associated with microvascular and macrovascular endothelial function, but a weak
      association was apparent between area under the curve for CRP and carotid
      atherosclerosis. CONCLUSIONS: Classical CVD risk factors may be better long-term
      predictors of vascular function and morphology than systemic disease-related
      inflammation in patients with RA. Further studies are needed to confirm if
      assessments of vascular function and morphology are predictive of long-term CV
      outcomes in RA.

PMID- 24289092
TI  - An unusual delayed complication of paraffin self-injection for penile girth
      augmentation.
AB  - BACKGROUND: Penile self-injection of various oils is still carried out among
      Eastern Europe people for penile girth augmentation despite the potential
      destructive complications of this practice are well known. Penile reactions to
      such foreign bodies include scarring, abscess formation, ulceration, and even
      Fournier's gangrene; voiding problems due to mineral oil self-injection have been
      reported only once. To our knowledge, we describe the first case of paraffin self
      injection for penile girth augmentation presenting with acute urinary retention.
      CASE PRESENTATION: A 27-year-old Romanian man presented with severe penile pain
      and acute urinary retention five years after having practiced repeated penile
      self-injections of paraffin for penile girth augmentation. The penile shaft was
      massively enlarged, fibrotic and phymotic; urethral catheterization failed due to
      severe stricture of the proximal pendulum urethra. The patients refused placement
      of a suprapubic catheter and underwent immediate penile surgical exploration. The
      scarred tissue between dartos and Buck's fascia and a fibrotic ring occluding the
      urethra were removed and the penile skin reconstructed. Pathology confirmed the
      diagnosis of paraffinoma. The patient resumed normal voiding immediately after
      catheter removal on second postoperative day; he was very pleased with cosmetic,
      sexual and voiding results at six weeks, six months and 1 year follow-up.
      CONCLUSIONS: The present report describes a novel complication of penile self
      injection for penile girth augmentation. Because of the increasing number of
      patients seeking penile augmentation, physicians dealing with sexual medicine
      should pay more attention to such request to prevent the use of non medical
      treatments that can turn into medical disasters.

PMID- 24289093
TI  - The impact of knowledge about diabetes, resilience and depression on glycemic
      control: a cross-sectional study among adolescents and young adults with type 1
      diabetes.
AB  - BACKGROUND: The purpose of this study is to evaluate the relationship between
      glycemic control and the factors of knowledge about diabetes, resilience,
      depression and anxiety among Brazilian adolescents and young adults with type 1
      diabetes. METHODS: This cross-sectional study included 85 adolescents and young
      adults with type 1 diabetes, aged between 11-22 years, with an average age of
      17.7 +/- 3.72 years. Glycemic control degree was evaluated through HbA1c. To
      assess psychosocial factors, the following questionnaires were used: resilience
      (Resilience Scale, RS) and anxiety and depression (Hospital Anxiety and
      Depression Scale, HADS). The Diabetes Knowledge Assessment Scale (DKNA) was used
      to assess knowledge about diabetes. RESULTS: Significant correlations were found
      between HbA1c and resilience, anxiety and depression. Multiple linear regression
      analysis revealed that the only variable which presented significant association
      with the value of HbA1c was depression. CONCLUSIONS: Depression has a significant
      association with higher HbA1c levels, as demonstrated in a regression analysis.
      The results suggest that depression, anxiety and resilience should be considered
      in the design of a multidisciplinary approach to type 1 diabetes, as these
      factors were significantly correlated with glycemic control. Glycemic control was
      not correlated with knowledge of diabetes, suggesting that theoretical or
      practical understanding of this disease is not by itself significantly associated
      with appropriate glycemic control (HbA1c = 7.5%).

PMID- 24289095
TI  - Delivery of HIV care during the 2007 post-election crisis in Kenya: a case study
      analyzing the response of the Academic Model Providing Access to Healthcare
      (AMPATH) program.
AB  - BACKGROUND: Widespread violence followed the 2007 presidential elections in Kenya
      resulting in the deaths of a reported 1,133 people and the displacement of
      approximately 660,000 others. At the time of the crisis the United States Agency
      for International Development-Academic Model Providing Access to Healthcare
      (USAID-AMPATH) Partnership was operating 17 primary HIV clinics in western Kenya
      and treating 59,437 HIV positive patients (23,437 on antiretroviral therapy
      (ART)). METHODS: This case study examines AMPATH's provision of care and
      maintenance of patients on ART throughout the period of disruption. This was
      accomplished by implementing immediate interventions including rapid information
      dissemination through the media, emergency hotlines and community liaisons;
      organization of a Crisis Response leadership team; the prompt assembly of
      multidisciplinary teams to address patient care, including psychological support
      staff (in clinics and in camps for internally displaced persons (IDP)); and the
      use of the AMPATH Medical Records System to identify patients on ART who had
      missed clinic appointments. RESULTS: These interventions resulted in the opening
      of all AMPATH clinics within five days of their scheduled post-holiday opening
      dates, 23,949 patient visits in January 2008 (23,259 previously scheduled),
      uninterrupted availability of antiretrovirals at all clinics, treatment of 1,420
      HIV patients in IDP camps, distribution of basic provisions, mobilization of
      outreach services to locate missing AMPATH patients and delivery of psychosocial
      support to 300 staff members and 632 patients in IDP camps. CONCLUSION: Key
      lessons learned in maintaining the delivery of HIV care in a crisis situation
      include the importance of advance planning to develop programs that can function
      during a crisis, an emphasis on a rapid programmatic response, the ability of
      clinics to function autonomously, patient knowledge of their disease, the use of
      community and patient networks, addressing staff needs and developing effective
      patient tracking systems.

PMID- 24289096
TI  - What could a strengthened right to health bring to the post-2015 health
      development agenda?: interrogating the role of the minimum core concept in
      advancing essential global health needs.
AB  - BACKGROUND: Global health institutions increasingly recognize that the right to
      health should guide the formulation of replacement goals for the Millennium
      Development Goals, which expire in 2015. However, the right to health's
      contribution is undercut by the principle of progressive realization, which links
      provision of health services to available resources, permitting states to deny
      even basic levels of health coverage domestically and allowing international
      assistance for health to remain entirely discretionary. DISCUSSION: To prevent
      progressive realization from undermining both domestic and international
      responsibilities towards health, international human rights law institutions
      developed the idea of non-derogable "minimum core" obligations to provide
      essential health services. While minimum core obligations have enjoyed some
      uptake in human rights practice and scholarship, their definition in
      international law fails to specify which health services should fall within their
      scope, or to specify wealthy country obligations to assist poorer countries.
      These definitional gaps undercut the capacity of minimum core obligations to
      protect essential health needs against inaction, austerity and illegitimate trade
      offs in both domestic and global action. If the right to health is to effectively
      advance essential global health needs in these contexts, weaknesses within the
      minimum core concept must be resolved through innovative research on social,
      political and legal conceptualizations of essential health needs. SUMMARY: We
      believe that if the minimum core concept is strengthened in these ways, it will
      produce a more feasible and grounded conception of legally prioritized health
      needs that could assist in advancing health equity, including by providing a
      framework rooted in legal obligations to guide the formulation of new health
      development goals, providing a baseline of essential health services to be
      protected as a matter of right against governmental claims of scarcity and
      inadequate international assistance, and empowering civil society to claim
      fulfillment of their essential health needs from domestic and global decision
      makers.

PMID- 24289094
TI  - Different evolutionary trends of swine H1N2 influenza viruses in Italy compared
      to European viruses.
AB  - European H1N2 swine influenza viruses (EU H1N2SIVs) arose from multiple
      reassortment events among human H1N1, human H3N2, and avian influenza viruses. We
      investigated the evolutionary dynamics of 53 Italian H1N2 strains by comparing
      them with EU H1N2 SIVs. Hemagglutinin (HA) phylogeny revealed Italian strains
      fell into four groups: Group A and B (41 strains) had a human H1 similar to EU
      H1N2SIVs, which probably originated in 1986. However Group B (38 strains) formed
      a subgroup that had a two-amino acid deletion at positions 146/147 in HA. Group C
      (11 strains) contained an avian H1 that probably originated in 1996, and Group D
      (1 strain) had an H1 characteristic of the 2009 pandemic strain. Neuraminidase
      (NA) phylogeny suggested a series of genomic reassortments had occurred. Group A
      had an N2 that originated from human H3N2 in the late 1970s. Group B had
      different human N2 that most likely arose from a reassortment with the more
      recent human H3N2 virus, which probably occurred in 2000. Group C had an avian
      like H1 combined with an N2 gene from one of EU H1N2SIVs, EU H3N2SIVs or Human
      H3N2. Group D was part of the EU H3N2SIVs clade. Although selection pressure for
      HA and NA was low, several positively selected sites were identified in both
      proteins, some of which were antigenic, suggesting selection influenced the
      evolution of SIV. The data highlight different evolutionary trends between
      European viruses and currently circulating Italian B strains and show the
      establishment of reassortant strains involving human viruses in Italian pigs.

PMID- 24289097
TI  - The reproductive strategy of a pollinator-limited Himalayan plant, Incarvillea
      mairei (Bignoniaceae).
AB  - BACKGROUND: Plants may adapt to alpine habitats by specialization in the
      reproductive strategy and functional aspects of their flowers and pollination
      systems. Alpine habitats reduce the opportunities for cross-pollination in a
      relatively high proportion of alpine plant species, and self-pollination may be
      favored in these adverse conditions. Here, we investigated the mating system and
      pollination of Incarvillea mairei, a perennial Himalayan herb typically found at
      altitudes between 3000 and 4500 m. RESULTS: Analyses of floral morphology,
      observation of plant-pollinator interactions, and hand pollination experiments
      were conducted in three natural populations. Outcrossing rates and effective
      numbers of pollen donors were assessed in 45 open-pollinated families by using
      progeny analysis based on seven microsatellite markers. Incarvillea mairei
      displayed a set of apparently specialized floral traits, the stigma is sensitive
      to touch and close immediately and its reopening allows a second opportunity for
      the receipt of pollen. The species is fully self-compatible but employs a
      predominantly outcrossing mating system according to parentage analysis (tm >
      0.9). Fruit set was low (26.3%), whereas seed set was high (67.2%), indicating
      that this species suffers pollinator limitation. Its main effective pollinator
      was Halictus sp., and visitation frequency was low. CONCLUSIONS: Floral features
      such as having a sensitive stigma and anther-prongs, in conjunction with
      pollinator behavior, function together contributing to a set of unique
      reproductive adaptations that enhance outcrossing success. The increased floral
      longevity and high pollination efficiency operated as compensatory mechanisms to
      counteract low pollinator visitation frequency.

PMID- 24289098
TI  - Cognition is only minimally impaired in Spinocerebellar ataxia type 14 (SCA14): a
      neuropsychological study of ten Norwegian subjects compared to intrafamilial
      controls and population norm.
AB  - BACKGROUND: There is an increasing awareness of the role of the cerebellum not
      only in motor, but also in cognitive and emotional functions. Spinocerebellar
      ataxia type 14 (SCA14) is an autosomal dominant hereditary ataxia characterized
      by a relatively pure cerebellar phenotype. Cognitive impairment has been reported
      in studies with phenotype descriptions of SCA14, but previous studies have been
      small without control groups, and no homogeneous and systematic test panel has
      been used. The objective of this study was to thoroughly characterize the
      neuropsychological profile in ten Norwegian SCA14 subjects compared to unaffected
      family members and population norm data. METHODS: Ten SCA14 subjects and ten
      intrafamilial unaffected age- and education-matched controls from two Norwegian
      families were included. The unaffected intrafamilial controls included six first
      degree relatives, two second degree relatives, and two spouses. General
      intellectual ability, memory, visuoperceptive skills, psychomotor speed,
      executive functions, depression and anxiety were examined using internationally
      standardized tests, with minimal need for manual response to avoid motor bias.
      RESULTS: No significant cognitive deficit was found in SCA14 subjects compared to
      intrafamilial controls. Verbal IQ, verbal executive function and psychomotor
      speed tended to be reduced in affected subjects, but previously reported non
      verbal executive dysfunction was not confirmed in this study. CONCLUSION: Only
      subtle cognitive impairment was found in SCA14 affected subjects. The current
      findings do not confirm earlier reports of cognitive dysfunction in SCA14, but
      does shows a mild impairment in specific verbal executive functions. Genotypic
      differences may partly account for this discrepancy, and further studies on
      larger materials are needed to verify the findings.

PMID- 24289099
TI  - Effectiveness and cost effectiveness of guided online treatment for patients with
      major depressive disorder on a waiting list for psychotherapy: study protocol of
      a randomized controlled trial.
AB  - BACKGROUND: Depressive disorders are highly prevalent and result in negative
      consequences for both patients and society. It is therefore important that these
      disorders are treated adequately. However, due to increased demand for mental
      healthcare and subsequent increased costs, it would be desirable to reduce costs
      associated with major depressive disorder while maintaining or improving the
      quality of care within the healthcare system. Introducing evidence-based online
      self-help interventions in mental healthcare might be the way to maintain
      clinical effects while minimizing costs by reducing the number of face-to-face
      sessions. This study aims to evaluate the clinical and economical effects of a
      guided online self-help intervention when offered to patients with major
      depressive disorder on a waiting list for psychotherapy in specialized mental
      health centers (MHCs). METHODS: Patients at mental health centers identified with
      a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)
      diagnosis of major depression who are awaiting face-to-face treatment are studied
      in a randomized controlled trial. During this waiting list period, patients are
      randomized and either (1) receive an internet-based guided self-help treatment or
      (2) receive a self-help book. The 5-week internet-based guided self-help
      intervention and the self-help booklet are based on problem solving treatment.
      After the intervention, patients are allowed to start regular face-to-face
      treatment at MHCs. Costs and effects are measured at baseline, after the
      intervention at 6 to 8 weeks, 6 months and 12 months. The primary outcome measure
      is symptoms of depression. Secondary outcome measures are diagnosis of
      depression, number of face-to-face sessions, absence of work and healthcare
      uptake in general. Additional outcome measures are anxiety, insomnia, quality of
      life and mastery. DISCUSSION: This study evaluates the effectiveness and cost
      effectiveness of internet-based guided self-help in patients at specialized
      mental health centers. The aim is to demonstrate whether the introduction of
      internet-based self-help interventions in regular mental healthcare for
      depressive disorders can maintain clinical effects and reduce costs. Strengths
      and limitations of this study are discussed. TRIAL REGISTRATION: Netherlands
      Trial Register NTR2824.

PMID- 24289100
TI  - Correlates of consistent condom use among men who have sex with men recruited
      through the Internet in Huzhou city: a cross-sectional survey.
AB  - BACKGROUND: There is growing evidence that men who have sex with men (MSM) are
      currently a group at high risk of HIV infection in China. Our study aims to know
      the factors affecting consistent condom use among MSM recruited through the
      internet in Huzhou city. METHODS: An anonymous cross-sectional study was
      conducted by recruiting 410 MSM living in Huzhou city via the Internet. The socio
      demographic profiles (age, education level, employment status, etc.) and sexual
      risk behaviors of the respondents were investigated. Bivariate logistic
      regression analyses were performed to compare the differences between consistent
      condom users and inconsistent condom users. Variables with significant bivariate
      between groups' differences were used as candidate variables in a stepwise
      multivariate logistic regression model. All statistical analyses were performed
      using SPSS for Windows 17.0, and a p value < 0.05 was considered to be
      statistically significant. RESULTS: According to their condom use, sixty-eight
      respondents were classified into two groups. One is consistent condom users, and
      the other is inconsistent condom users. Multivariate logistic regression showed
      that respondents who had a comprehensive knowledge of HIV (OR = 4.08, 95% CI:
      1.85-8.99), who had sex with male sex workers (OR = 15.30, 95% CI: 5.89-39.75)
      and who had not drunk alcohol before sex (OR = 3.10, 95% CI: 1.38-6.95) were more
      likely to be consistent condom users. CONCLUSIONS: Consistent condom use among
      MSM was associated with comprehensive knowledge of HIV and a lack of alcohol use
      before sexual contact. As a result, reducing alcohol consumption and enhancing
      education regarding the risks of HIV among sexually active MSM would be effective
      in preventing of HIV transmission.

PMID- 24289101
TI  - B lymphocytes and B-cell activating factor promote collagen and profibrotic
      markers expression by dermal fibroblasts in systemic sclerosis.
AB  - INTRODUCTION: B lymphocytes might play a pathogenic role in dermal fibrosis in
      systemic sclerosis (SSc). B-cell activating factor (BAFF), a key cytokine for B
      cell activation, is increased in the serum and the skin of patients with SSc.
      However, the ability of B cells directly to stimulate dermal fibroblasts and the
      role of BAFF are not fully understood. We therefore investigated the involvement
      of B cells and BAFF in the expression of collagen and profibrotic markers by
      dermal fibroblasts. METHODS: Cocultures of blood B cells from healthy blood
      donors and normal or SSc dermal fibroblasts stimulated with anti-IgM and BAFF
      were performed. Alpha-SMA, TIMP1, MMP9, COL1A1, COL1A2, and COL3A1 mRNA
      expression were determined by quantitative RT-PCR. Soluble collagen, BAFF, IL-6,
      IL-1beta, TGF-beta1, and CCL2 protein secretion were assessed. RESULTS: Coculture
      of blood B cells and dermal fibroblasts isolated from SSc patients induced IL-6,
      TGF-beta1, CCL2, and collagen secretion, as well as Alpha-SMA, TIMP1, and MMP9
      expression in dermal fibroblasts. Transwell assays demonstrated that this
      induction was dependent on cell-cell contact. Addition of anti-IgM and BAFF to
      the coculture increased IL-6, CCL2, TGF-beta1, and collagen secretion. B cell-
      and BAFF-induced collagen secretion was highly reduced by anti-TGF-beta1
      antibodies. CONCLUSIONS: Our results showed for the first time a direct role of B
      cells on the production of collagen by dermal fibroblasts, which is further
      enhanced by BAFF. Thus, these results demonstrate a new pathogenic role of B
      cells and BAFF in fibrosis and systemic sclerosis.

PMID- 24289102
TI  - Interstitial lung disease associated with Equine Infectious Anemia Virus
      infection in horses.
AB  - EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by
      haematophagous insects or needle punctures. Other routes of transmission have
      been poorly explored. We evaluated the potential of EIAV (Equine Infectious
      Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs
      from 77 EIAV seropositive horses have been collected in Romania and France. Three
      types of lesions have been scored on paraffin-embedded lungs: lymphocyte
      infiltration, bronchiolar inflammation, and thickness of the alveolar septa.
      Expression of the p26 EIAV capsid (CA) protein has been evaluated by
      immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses
      displayed a mild inflammation around the bronchioles, 22% had a moderate
      inflammation with inflammatory cells inside the wall and epithelial bronchiolar
      hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of
      the bronchiolar epithelium and accumulation of smooth muscle cells within the
      pulmonary parenchyma. Changes in the thickness of the alveolar septa were also
      present. Expression of EIAV capsid has been evidenced in macrophages, endothelial
      as well as in alveolar and bronchiolar epithelial cells, as determined by their
      morphology and localization. To summarize, we found lesions of interstitial lung
      disease similar to that observed during other lentiviral infections such as FIV
      in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid
      in lung epithelial cells suggests that EIAV might be responsible for the broncho
      interstitial damages observed.

PMID- 24289103
TI  - GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer.
AB  - INTRODUCTION: Tamoxifen is widely used to treat hormone-dependent breast cancer,
      but its therapeutic benefit is limited by the development of drug resistance.
      Here, we investigated the role of estrogen G-protein coupled receptor 30 (GPR30)
      on Tamoxifen resistance in breast cancer. METHODS: Primary tumors (PTs) of breast
      cancer and corresponding metastases (MTs) were used to evaluate the expression of
      GPR30 and epidermal growth factor receptor (EGFR) immunohistochemically.
      Tamoxifen-resistant (TAM-R) subclones derived from parent MCF-7 cells were used
      to investigate the role of GPR30 in the development of tamoxifen resistance,
      using MTT assay, western blot, RT-PCR, immunofluorescence, ELISA and flow
      cytometry. TAM-R xenografts were established to assess anti-tumor effects of
      combination therapy with GPR30 antagonist G15 plus 4-hydroxytamoxifen (Tam),
      using tumor volume measurement and Terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL). RESULTS: In 53 human breast cancer specimens, GPR30
      expression in MTs increased compared to matched PTs; in MTs, the expression
      patterns of GPR30 and EGFR were closely related. Compared to parent MCF-7 cells,
      TAM-R cells had greater growth responses to 17beta-estradiol (E2), GPR30 agonist
      G1 and Tam, and significantly higher activation of Mitogen-activated protein
      (MAP) kinases; but this increased activity was abolished by G15 or AG1478. In TAM
      R cells, GPR30 cell-surface translocation facilitated crosstalk with EGFR, and
      reduced cAMP generation, attenuating inhibition of EGFR signaling. Combination
      therapy both promoted apoptosis in TAM-R cells and decreased drug-resistant tumor
      progression. CONCLUSIONS: Long-term endocrine treatment facilitates the
      translocation of GPR30 to cell surfaces, which interferes with the EGFR signaling
      pathway; GPR30 also attenuates the inhibition of MAP kinases. These factors
      contribute to tamoxifen resistance development in breast cancer. Combination
      therapy with GPR30 inhibitors and tamoxifen may provide a new therapeutic option
      for drug-resistant breast cancer.

PMID- 24289104
TI  - Relationships between perioperative physical activity and urinary incontinence
      after radical prostatectomy: an observational study.
AB  - BACKGROUND: Higher physical activity levels are continence-protective in non
      prostate cancer populations. Primary aims of this study were to investigate
      changes in physical activity levels over the perioperative period in patients
      having radical prostatectomy, and relationships between perioperative physical
      activity levels and post-prostatectomy urinary incontinence. METHODS: A
      prospective analysis of patients having radical prostatectomy and receiving
      perioperative physiotherapy including pelvic floor muscle training and physical
      activity prescription (n = 33). Physical activity levels were measured using the
      International Physical Activity Questionnaire and/or the SenseWear Pro3 Armband
      at four timepoints: before preoperative physiotherapy, the week before surgery,
      and 3 and 6 weeks postoperatively. Urinary incontinence was measured at 3 and 6
      weeks postoperatively using a 24-hour pad test and the International Consultation
      on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ). RESULTS:
      Physical activity levels changed significantly over the perioperative period (p <
      0.001). At 6 weeks postoperatively, physical activity levels did not differ
      significantly from baseline (p = 0.181), but remained significantly lower than
      the week before surgery (p = 0.002). There was no significant interaction effect
      between preoperative physical activity category and time on the 24-hour pad test
      (p = 0.726) or ICIQ (p = 0.608). Nor were there any significant correlations
      between physical activity levels and the 24-hour pad test and ICIQ at 3 or 6
      weeks postoperatively. CONCLUSIONS: This study provides novel data on
      perioperative physical activity levels for patients having radical prostatectomy.
      There was no relationship between perioperative physical activity levels and post
      prostatectomy urinary incontinence, although participants had high overall
      preoperative physical activity levels and low overall urinary incontinence.

PMID- 24289105
TI  - Reticulocyte-prone malaria parasites predominantly invade CD71hi immature cells:
      implications for the development of an in vitro culture for Plasmodium vivax.
AB  - BACKGROUND: The lack of a continuous in vitro culture system for blood stages of
      malarial parasites with a unique tropism for reticulocytes, such as Plasmodium
      vivax and the Plasmodium yoelii 17X reticulocyte-prone strain, hinders research
      in these organisms. The maturation of reticulocytes into erythrocytes is a
      complex process involving the selective removal of membrane proteins such as the
      transferrin receptor, CD71. In order to advance in the characterization of
      infected cells during experimental infections of BALB/c mice with P. yoelii 17X,
      CD71 expression in erythroid cells (TER119+) was assessed and in vitro culture of
      P. yoelii 17X was attempted by adding reticulocytes highly expressing CD71.
      METHODS: BALB/c mice were infected with P. yoelii 17X-GFP transgenic parasites
      and erythroid cells (TER119+) were analysed in blood, spleen and bone marrow
      cells. TER119, CD71 and GFP expression was assessed at different points post
      infection by flow cytometry. Moreover, in vitro culture of P. yoelli 17X was
      attempted by adding red blood cells (RBCs) from mice with a pyruvate kinase
      deficiency, which contain high percentages of CD71hi cells in peripheral blood as
      compared to healthy animals. RESULTS: A predominance of erythroid cells lacking
      expression of CD71 (CD71-) was observed in peripheral blood and spleen in normal
      and infected animals up to ten days post-infection (pi). At ten days pi, however,
      a dramatic temporal switch to erythroid cells highly expressing CD71 (CD71hi) was
      observed in the spleen and at day 15 pi in peripheral blood of the infected
      cells. A distribution of erythroid cells expressing differently CD71 was noticed
      in the bone marrow. Yet, similar to peripheral blood and spleen, a predominance
      of CD71hi cells was observed at 15 days pi. Remarkably, CD71hi cells were the
      cells predominantly infected in these organs as well as in peripheral blood.
      Attempts were thus made to culture in vitro the P. yoelli 17X strain by adding
      RBCs from pyruvate kinase-deficient mice containing high percentages of CD71hi
      cells in peripheral blood. CONCLUSIONS: The parasite preference for immature
      cells that are rare in normal peripheral blood could have important implications
      for the development of an in vitro culture system for P. vivax.

PMID- 24289106
TI  - Flavonoid-based pH-responsive hydrogels as carrier of unstable drugs in oxidative
      conditions.
AB  - In this study, pH-responsive hydrogels, synthesized by the coupling reaction of
      polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward
      the GI tract. The presence of polyphenolic moieties in the network gives the
      polymers properties suitable for the release of unstable drugs in oxidative
      conditions. The characterization of the hydrogels is obtained by means of
      morphological and physico-chemical analyses, antioxidant assays and evaluation of
      the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal
      (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro
      release studies of folic acid and thiamine, two model drugs easily degraded by
      oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide
      treatment, respectively. Results show that catechin-based carriers are able to
      control the release of drugs at different pH values, giving a remarkable
      improvement in the stability of the therapeutics. 

PMID- 24289107
TI  - Identification of pharmacogenomic markers of clinical efficacy in a dose-dense
      therapy regimen (R-CHOP14) in diffuse large B-cell lymphoma.
AB  - About 60% of patients with diffuse large B-cell lymphoma (DLBCL) may be cured by
      primary chemotherapy with an R-CHOP (rituximab, cyclophosphamide, doxorubicin,
      vincristine, prednisone) regimen. Most of the rest will die of the disease,
      mainly due to the occurrence of tumor drug resistance. Many efforts have been
      made to explain the molecular mechanisms of drug resistance in patients with
      cancer, including those with DLBCL. This exploratory study was designed to
      correlate the mRNA expression levels of candidate genes mainly involved in the
      doxorubicin pathway (ABCB1, GSTP1, TOPO2alpha, BCL2, PKCbetaII) with the outcome
      of 54 patients with DLBCL undergoing a dose-dense R-CHOP regimen. After
      multivariate analysis, high GSTP1 (p = 0.003) and TOPO2alpha (p = 0.02) gene
      expressions were associated with shorter overall survival and progression-free
      survival, respectively, suggesting that these genes may represent an unfavorable
      prognostic factor in the case of R-CHOP treatment. These biomarkers may be useful
      for selecting patients eligible for personalized chemotherapy after validation in
      an independent set.

PMID- 24289108
TI  - Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation
      of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic
      phase.
AB  - Asian patients with chronic myeloid leukemia (CML) tend to have different
      characteristics compared with patients from other regions, including younger age
      and smaller body size. The phase 3, open-label, randomized DASISION trial
      (NCT00481247), comparing dasatinib 100 mg once daily (QD) (n = 259) with imatinib
      400 mg QD (n = 260) in newly diagnosed chronic phase CML (CML-CP), included a
      sizeable East Asian population (n = 60: dasatinib; n = 48: imatinib). In East
      Asian patients, dasatinib showed favorable 24-month rates of major molecular
      response (68% vs. 50% for imatinib) and complete cytogenetic response (92% vs.
      88%), and more patients achieved BCR-ABL1 transcript levels <= 10% at 3 months
      with dasatinib (91% vs. 69%), similar to the overall population. Relative to non
      East Asian patients, the incidence of rash, fluid-related events and grade 3/4
      neutropenia and thrombocytopenia appeared to be higher in East Asians, regardless
      of treatment. Pharmacokinetic analysis revealed statistically non-significant
      increased dasatinib exposure among East Asian patients. Results support the use
      of dasatinib 100 mg QD as first-line CML treatment in both East Asian and non
      East Asian patients.

PMID- 24289109
TI  - Cell surface phenotype profiles distinguish stable and progressive chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is clinically heterogeneous. While some
      patients have indolent disease for many years, 20-30% will progress and
      ultimately die of their disease. CLL may be classified by the Rai or Binet
      staging system, mutational status of the immunoglobulin variable heavy-chain gene
      (IGVH), ZAP-70 overexpression, cytogenetic abnormalities (13q-, + 12, 11q-, 17p-)
      and expression of several cell surface antigens (CD38, CD49d) that correlate with
      risk of disease progression. However, none of these markers identify all cases of
      CLL at risk. In a recent review, we summarized those CD antigens known to
      correlate with the prognosis of CLL. The present study has identified surface
      profiles of CD antigens that distinguish clinically progressive CLL from slow
      progressive and stable CLL. Using an extended DotScan(TM) CLL antibody microarray
      (Version 3; 182 CD antibodies), and with refined analysis of purified CD19 + B
      cells, the following 27 CD antigens were differentially abundant for progressive
      CLL: CD11a, CD11b, CD11c, CD18, CD19, CD20 (two epitopes), CD21, CD22, CD23,
      CD24, CD25, CD38, CD40, CD43, CD45, CD45RA, CD52, CD69, CD81, CD84, CD98, CD102,
      CD148, CD180, CD196 and CD270. The extensive surface profiles obtained provide
      disease signatures with an accuracy of 79.2%, a sensitivity of 83.9% and a
      specificity of 72.5% that could provide the basis for a rapid test to triage
      patients with CLL according to probability of clinical progression and potential
      earlier requirement for treatment.

PMID- 24289110
TI  - Correlation between mass transfer coefficient kLa and relevant operating
      parameters in cylindrical disposable shaken bioreactors on a bench-to-pilot
      scale.
AB  - BACKGROUND: Among disposable bioreactor systems, cylindrical orbitally shaken
      bioreactors show important advantages. They provide a well-defined hydrodynamic
      flow combined with excellent mixing and oxygen transfer for mammalian and plant
      cell cultivations. Since there is no known universal correlation between the
      volumetric mass transfer coefficient for oxygen kLa and relevant operating
      parameters in such bioreactor systems, the aim of this current study is to
      experimentally determine a universal kLa correlation. RESULTS: A Respiration
      Activity Monitoring System (RAMOS) was used to measure kLa values in cylindrical
      disposable shaken bioreactors and Buckingham's pi-Theorem was applied to define a
      dimensionless equation for kLa. In this way, a scale- and volume-independent kLa
      correlation was developed and validated in bioreactors with volumes from 2 L to
      200 L. The final correlation was used to calculate cultivation parameters at
      different scales to allow a sufficient oxygen supply of tobacco BY-2 cell
      suspension cultures. CONCLUSION: The resulting equation can be universally
      applied to calculate the mass transfer coefficient for any of seven relevant
      cultivation parameters such as the reactor diameter, the shaking frequency, the
      filling volume, the viscosity, the oxygen diffusion coefficient, the
      gravitational acceleration or the shaking diameter within an accuracy range of +/
      30%. To our knowledge, this is the first kLa correlation that has been defined
      and validated for the cited bioreactor system on a bench-to-pilot scale.

PMID- 24289111
TI  - Process evaluation of the Teamplay parenting intervention pilot: implications for
      recruitment, retention and course refinement.
AB  - BACKGROUND: Parenting programs could provide effective routes to increasing
      children's physical activity and reducing screen-viewing. Many studies have
      reported difficulties in recruiting and retaining families in group parenting
      interventions. This paper uses qualitative data from the Teamplay feasibility
      trial to examine parents' views on recruitment, attendance and course refinement.
      METHODS: Semi-structured interviews were conducted with 16 intervention and 10
      control group parents of 6-8 year old children. Topics discussed with the
      intervention group included parents' views on the recruitment, structure, content
      and delivery of the course. Topics discussed with the control group included
      recruitment and randomization. Interviews were digitally recorded, transcribed
      and thematically analyzed. RESULTS: Many parents in both the intervention and
      control group reported that they joined the study because they had been thinking
      about ways to improve their parenting skills, getting ideas on how to change
      behavior, or had been actively looking for a parenting course but with little
      success in enrolling on one. Both intervention and control group parents reported
      that the initial promotional materials and indicative course topics resonated
      with their experiences and represented a possible solution to parenting
      challenges. Participants reported that the course leaders played an important
      role in helping them to feel comfortable during the first session, engaging
      anxious parents and putting parents at ease. The most commonly reported reason
      for parents returning to the course after an absence was because they wanted to
      learn new information. The majority of parents reported that they formed good
      relationships with the other parents in the group. An empathetic interaction
      style in which leaders accommodated parent's busy lives appeared to impact
      positively on course attendance. CONCLUSIONS: The data presented indicate that a
      face-to-face recruitment campaign which built trust and emphasized how the
      program was relevant to families positively affected recruitment in Teamplay.
      Parents found the parenting component of the intervention attractive and, once
      recruited, attendance was facilitated by enjoyable sessions, empathetic leaders
      and support from fellow participants. Overall, data suggest that the Teamplay
      recruitment and retention approaches were successful and with small refinements
      could be effectively used in a larger trial.

PMID- 24289112
TI  - Detection of Brucella abortus DNA and RNA in different stages of development of
      the sucking louse Haematopinus tuberculatus.
AB  - BACKGROUND: Brucellosis is considered the world's most widespread zoonotic
      infection. It causes abortion and sterility in livestock leading to serious
      economic losses and has even more serious medical impact in humans, since it can
      be a trigger to more than 500,000 infections per year worldwide. The aim of this
      study was to evaluate the role of Haematopinus tuberculatus, a louse that can
      parasitize several ruminants, as a new host of brucellosis. Louse specimens were
      collected from seropositive and seronegative water buffaloes and divided in 3
      developmental stages: adults, nymphs and nits. All samples were separately
      screened for Brucella spp. DNA and RNA detection by Real Time PCR. In particular,
      primers and probes potentially targeting the 16S rRNA and the Brucella Cell
      Surface 31 kDalton Protein (bcsp31) genes were used for Real Time PCR and buffalo
      beta actin was used as a housekeeping gene to quantify host DNA in the sample. A
      known amount of B. abortus purified DNA was utilized for standard curve
      preparation and the target DNA amount was divided by the housekeeping gene amount
      to obtain a normalized target value. A further molecular characterization was
      performed for Brucella strain typing and genotyping by the Bruce-ladder, AMOS-PCR
      and MLVA assays. Data were statistically analysed by ANOVA. RESULTS: Brucella
      abortus DNA and RNA were detected in all developmental stages of the louse,
      suggesting the presence of viable bacteria. Data obtained by MLVA
      characterization support this finding, since the strains present in animals and
      the relative parasites were not always identical, suggesting bacterial
      replication. Furthermore, the detection of Brucella DNA and RNA in nits samples
      demonstrate, for the first time, a trans-ovarial transmission of the bacterium
      into the louse. CONCLUSIONS: These findings identified H. tuberculatus as a new
      host of brucellosis. Further studies are needed to establish the role of this
      louse in the epidemiology of the disease, such as vector or reservoir.

PMID- 24289113
TI  - Friendship networks and physical activity and sedentary behavior among youth: a
      systematized review.
AB  - BACKGROUND: Low levels of physical activity and increased participation in
      sedentary leisure-time activities are two important obesity-risk behaviors that
      impact the health of today's youth. Friend's health behaviors have been shown to
      influence individual health behaviors; however, current evidence on the specific
      role of friendship networks in relation to levels of physical activity and
      sedentary behavior is limited. The purpose of this review was to summarize
      evidence on friendship networks and both physical activity and sedentary behavior
      among children and adolescents. METHOD: After a search of seven scientific
      databases and reference scans, a total of thirteen articles were eligible for
      inclusion. All assessed the association between friendship networks and physical
      activity, while three also assessed sedentary behavior. RESULTS: Overall, higher
      levels of physical activity among friends are associated with higher levels of
      physical activity of the individual. Longitudinal studies reveal that an
      individual's level of physical activity changes to reflect his/her friends'
      higher level of physical activity. Boys tend to be influenced by their friendship
      network to a greater extent than girls. There is mixed evidence surrounding a
      friend's sedentary behavior and individual sedentary behavior. CONCLUSION:
      Friends' physical activity level appears to have a significant influence on
      individual's physical activity level. Evidence surrounding sedentary behavior is
      limited and mixed. Results from this review could inform effective public health
      interventions that harness the influence of friends to increase physical activity
      levels among children and adolescents.

PMID- 24289114
TI  - Self-(in)compatibility genotypes of Moroccan apricots indicate differences and
      similarities in the crop history of European and North African apricot germplasm.
AB  - BACKGROUND: Allelic diversity of the S-locus is attributed to the genetic
      relationships among genotypes and sexual reproduction strategy. In otherwise self
      incompatible Prunus species, the emergence of loss-of-function in S-haplotypes
      has resulted in self-compatibility. This information may allow following major
      stages of crop history. The genetic diversity in the S-locus of local apricots
      (Prunus armeniaca L.) from different oasis ecosystems in Morocco and the
      comparison of the occurrence and frequency of S-alleles with other regions may
      allow testing the validity of previous theories on the origin and dissemination
      of North African apricots. RESULTS: The S-genotypes of 55 Moroccan apricot
      accessions were determined, resulting in 37 self-compatible genotypes, from which
      33 were homozygotes for self-compatibility. SC was the most frequent S-allele in
      this germplasm, followed by S13, S7, S11, S2, S20, S8, and S6. New approaches
      (CAPS or allele-specific PCR) were designed for a reliable verification of the
      rare or unexpected alleles. The frequency and distribution of the S-alleles
      differed among the oases. Some of these alleles, S8, S11, S13 and S20, were
      formerly detected only in the Irano Caucasian germplasm and are not present in
      Europe. CONCLUSIONS: Our data supports the Irano-Caucasian origin of the Moroccan
      apricots and their original introduction by Phoenicians and Arabs through the
      North African shore. North Africa seems to have preserved much higher variability
      of apricot as compared with Europe. The loss of genetic diversity in apricot
      might be explained by the occurrence of self-compatibility and the length of time
      that apricot has spent with this breeding system in an environment without its
      wild relatives, such as the Moroccan oases or Central Europe.

PMID- 24289115
TI  - LncRNA DQ786243 affects Treg related CREB and Foxp3 expression in Crohn's
      disease.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have different functions in cells.
      They work as signals, decoys, guides, and scaffolds. Altered lncRNA levels can
      affect the expression of gene products. There are seldom studies on the role of
      lncRNAs in inflammatory bowel disease (IBD). RESULTS: Quantitative RT-PCR showed
      that DQ786243 was significantly overexpressed in clinical active CD patients
      compared with clinical inactive CD patients (P = 0.0118) or healthy controls (P =
      0.002). CREB was also more highly expressed in active CD than in inactive CD (P =
      0.0034) or controls (P = 0.0241). Foxp3 was interestingly lower in inactive CD
      than in active CD (P = 0.0317) or controls (P = 0.0103), but there were no
      apparent differences between active CD and controls. CRP was well correlated with
      DQ786243 (r = 0.489, P = 0.034), CREB (r = 0.500, P = 0.029) and Foxp3 (r =
      0.546, P = 0.016). At 48 hours after DQ786243 transfection, qRT-PCR showed both
      CREB (P = 0.017) and Foxp3 (P = 0.046) had an increased mRNA expression in Jurkat
      cells. Western blot showed the same pattern. After DQ786243 transfection, CREB
      phosphorylation ratio (p-CREB/t-CREB) was increased (P = 0.0043). CONCLUSION:
      DQ786243 can be related with severity of CD. It can affect the expression of CREB
      and Foxp3 through which regulates the function of Treg. CREB itself seems not the
      mediator of DQ786243 to up-regulate Foxp3. The phosphorylation of CREB might play
      a more important role in the process.

PMID- 24289117
TI  - A proposed grading system for standardizing tumor consistency of intracranial
      meningiomas.
AB  - OBJECT: Tumor consistency plays an important and underrecognized role in the
      surgeon's ability to resect meningiomas, especially with evolving trends toward
      minimally invasive and keyhole surgical approaches. Aside from descriptors such
      as "hard" or "soft," no objective criteria exist for grading, studying, and
      conveying the consistency of meningiomas. METHODS: The authors designed a
      practical 5-point scale for intraoperative grading of meningiomas based on the
      surgeon's ability to internally debulk the tumor and on the subsequent resistance
      to folding of the tumor capsule. Tumor consistency grades and features are as
      follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft
      tumor, internal debulking mostly with suction, and remaining fibrous strands
      resected with easily folded capsule; 3) average consistency, tumor cannot be
      freely suctioned and requires mechanical debulking, and the capsule then folds
      with relative ease; 4) firm tumor, high degree of mechanical debulking required,
      and capsule remains difficult to fold; and 5) extremely firm, calcified tumor,
      approaches density of bone, and capsule does not fold. Additional grading
      categories included tumor heterogeneity (with minimum and maximum consistency
      scores) and a 3-point vascularity score. This grading system was prospectively
      assessed in 50 consecutive patients undergoing craniotomy for meningioma
      resection by 2 surgeons in an independent fashion. Grading scores were subjected
      to a linear weighted kappa analysis for interuser reliability. RESULTS: Fifty
      patients (100 scores) were included in the analysis. The mean maximal tumor
      diameter was 4.3 cm. The distribution of overall tumor consistency scores was as
      follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%.
      Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous
      tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of
      grades. The kappa analysis score for overall tumor consistency grade was 0.87 (SE
      0.06, 95% CI 0.76-0.99), with 90% user agreement. Kappa analysis scores for
      minimum and maximum grades of tumor regions were 0.69 (agreement 72%) and 0.75
      (agreement 78%), respectively. The kappa analysis score for tumor vascularity
      grading was 0.56 (agreement 76%). Overall consistency did not correlate with
      patient age, tumor location, or tumor size. A higher tumor vascularity grade was
      associated with a larger tumor diameter (p = 0.045) and with skull base location
      (p = 0.02). CONCLUSIONS: The proposed grading system provides a reliable,
      practical, and objective assessment of meningioma consistency and facilitates
      communication among providers. This system also accounts for heterogeneity in
      tumor consistency. With the proposed scale, meningioma consistency can be
      standardized as groundwork for future studies relating to surgical outcomes,
      predictability of consistency and vascularity using neuroimaging techniques, and
      effectiveness of various surgical instruments.

PMID- 24289116
TI  - A novel risk score to predict 1-year functional outcome after intracerebral
      hemorrhage and comparison with existing scores.
AB  - INTRODUCTION: Spontaneous intracerebral hemorrhage (ICH) is one of leading causes
      of mortality and morbidity worldwide. Several predictive models have been
      developed for ICH; however, none of them have been consistently used in routine
      clinical practice or clinical research. In the study, we aimed to develop and
      validate a risk score for predicting 1-year functional outcome after ICH (ICH
      Functional Outcome Score, ICH-FOS). Furthermore, we compared discrimination of
      the ICH-FOS and 8 existing ICH scores with regard to 30-day, 3-month, 6-month,
      and 1-year functional outcome and mortality after ICH. METHODS: The ICH-FOS was
      developed based on the China National Stroke Registry, in which eligible patients
      were randomly divided into derivation (60%) and validation (40%) cohorts. Poor
      functional outcome was defined as modified Rankin Scale score (mRS) >=3 at 1 year
      after ICH. Multivariable logistic regression was performed to determine
      independent predictors, and beta-coefficients were used to generate scoring
      system of the ICH-FOS. The area under the receiver operating characteristic curve
      (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model
      discrimination and calibration. RESULTS: The overall 1-year poor functional
      outcome (mRS >= 3) was 46.7% and 44.9% in the derivation (n = 1,953) and
      validation (n = 1,302) cohorts, respectively. A 16-point ICH-FOS was developed
      from the set of independent predictors of 1-year poor functional outcome after
      ICH including age (P < 0.001), admission National Institutes of Health Stroke
      Scale score (P < 0.001), Glasgow Coma Scale score (P < 0.001), blood glucose (P =
      0.002), ICH location (P < 0.001), hematoma volume (P < 0.001), and
      intraventricular extension (P < 0.001). The ICH-FOS showed good discrimination
      (AUROC) in the derivation (0.836, 95% CI: 0.819-0.854) and validation (0.830, 95%
      CI: 0.808-0.852) cohorts. The ICH-FOS was well calibrated (Hosmer-Lemeshow test)
      in the derivation (P = 0.42) and validation (P = 0.39) cohort. When compared to 8
      prior ICH scores, the ICH-FOS showed significantly better discrimination with
      regard to 1-year functional outcome and mortality after ICH (all P < 0.0001).
      Meanwhile, the ICH-FOS also demonstrated either comparable or significantly
      better discrimination for poor functional outcome and mortality at 30-day, 3
      month, and 6-month after ICH. CONCLUSION: The ICH-FOS is a valid clinical grading
      scale for 1-year functional outcome after ICH. Further validation of the ICH-FOS
      in different populations is needed.

PMID- 24289118
TI  - Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort.
AB  - OBJECT: Tumors of the cerebellopontine angle (CPA) have always proven difficult
      for neurosurgeons to optimally manage. Studies investigating the natural history
      and treatment of vestibular schwannomas have dominated the literature in this
      regard. Distinguishing meningiomas from schwannomas in this location carries
      particular importance as each tumor type has certain prognostic and surgical
      considerations. In this study, the authors have characterized the outcomes of 34
      patients surgically treated for CPA meningiomas and have investigated various
      factors that may affect postoperative neurological function. METHODS: The medical
      records of patients with CPA meningiomas who underwent surgery from 2005 to 2013
      at the Duke University Health System were reviewed. Various patient, clinical,
      and tumor data were gathered from the medical records including patient
      demographics, pre- and postoperative neurological examinations, duration of
      symptoms, procedural details, tumor pathology and size, and treatment
      characteristics. Differences in continuous variables were then analyzed using the
      Student t-test while categorical variables were evaluated using the chi-square
      test. RESULTS: A total of 34 patients underwent surgical treatment for CPA
      meningiomas during the 8-year period. Jugular foramen invasion was seen in 17.6%
      of tumors, with nearly half (41.2%) extending into the internal acoustic canal.
      The most common presenting symptom was hearing loss (58.8%), followed by headache
      (52.9%) and facial numbness/pain (50.0%). The most common cranial nerve (CN)
      affected was CN X (11.8%), followed by CNs VI and VII (5.9%). Postoperatively, no
      patients experienced a decrease in hearing, with only 5.9% of patients
      experiencing facial nerve palsies. Patients with tumors larger than 3 cm had a
      significantly higher incidence of permanent CN deficits than those with smaller
      tumors (45.5% vs 5.9%, respectively; p = 0.011). Also, tumor extension into the
      jugular foramen was associated with the occurrence of lower CN deficits, none of
      which occurred in tumors without jugular foramen invasion. Internal acoustic
      canal tumor extension was not seen to be associated with postoperative
      complications or CN deficits. CONCLUSIONS: Meningiomas of the CPA are challenging
      lesions to treat surgically. However, the risk of facial palsy and hearing loss
      is significantly lower when compared with vestibular schwannomas. Novel methods
      for preoperative differentiation are needed to appropriately counsel patients on
      surgical risks. Also, due to the significant potential for neurological deficits,
      further studies are needed to investigate the utility of radiotherapy for these
      lesions.

PMID- 24289119
TI  - Petroclival meningiomas: an update on surgical approaches, decision making, and
      treatment results.
AB  - OBJECT: Petroclival meningiomas remain a formidable challenge for neurosurgeons
      because of their location deep within the skull base and proximity to eloquent
      neurovascular structures. Various skull base approaches have been used in their
      treatment, and deciding which is the optimal one remains controversial. Attempts
      at achieving gross- or near-total resections are associated with an increased
      rate of morbidity and mortality. As adjunctive treatment options such as
      stereotactic radiosurgery have been developed and become widely available, there
      has been a trend toward accepting subtotal resections in an effort to minimize
      neurological morbidity. This paper reviews a recent series of patients with
      petroclival meningiomas and highlights current management trends and important
      considerations useful in surgical decision making. METHODS: The records of
      patients with large (> 3 cm) petroclival meningiomas surgically treated by the
      senior author over the past 5 years were reviewed. The clinical results are
      presented as examples of the surgical approaches available for approaching these
      tumors, and treatment options are reviewed. RESULTS: Of 196 meningiomas
      surgically treated during the study period, 8 lesions in 8 patients met the study
      criteria. Overall clinical results were excellent, with no death or major
      morbidity. Intracranial gross- or near-total resection (Simpson Grade 1, 2, or 3)
      was achieved in 5 patients (67%). New cranial nerve deficits occurred in 3
      patients (37%) and were more common in patients in whom a subtotal resection was
      performed (2 of 3 cases). A variety of surgical approaches were used. Important
      considerations determining the best approach include the location of the tumor
      relative to the internal auditory canal, the presence of preoperative hearing
      loss, and the location of the tumor relative to the tentorium. CONCLUSIONS:
      Achieving gross- or near-total resections of large petroclival meningiomas
      remains achievable and should be the primary goal of surgical treatment. A
      retrosigmoid craniotomy remains a workhorse surgical approach for most
      petroclival tumors of any size. Tumors that are medial to the internal auditory
      canal and span both middle and posterior cranial fossae are often best treated
      with a combined transpetrosal approach, which is especially true if there is a
      preoperative hearing deficit.

PMID- 24289120
TI  - The far-lateral approach for foramen magnum meningiomas.
AB  - Foramen magnum meningiomas (FMMs) are slow growing, most often intradural and
      extramedullary tumors that pose significant challenges to the skull base
      neurosurgeon. The indolent clinical course of FMMs and their insidious onset of
      symptoms are important factors that contribute to delayed diagnosis and relative
      large size at the time of presentation. Symptoms are often produced by
      compression of surrounding structures (such as the medulla oblongata, upper
      cervical spinal cord, lower cranial nerves, and vertebral artery) within a
      critically confined space. Since the initial pathological description of a FMM in
      1872, various surgical approaches have been described with the aim of achieving
      radical tumor resection. The surgical treatment of FMMs has evolved considerably
      over the last 4 decades due to the progress in microsurgical techniques and
      development of a multitude of skull base approaches. Posterior and posterolateral
      FMMs can be safely resected via a standard midline suboccipital approach.
      However, controversy still exits regarding the optimal management of anterior or
      anterolateral lesions. Independently of technical variations and the degree of
      bone removal, all modern surgical approaches to the lower clivus and anterior
      foramen magnum derive from the posterolateral (or far-lateral) craniotomy
      originally described by Roberto Heros and Bernard George. This paper is a review
      of the surgical management of FMMs, with emphasis on the far-lateral approach and
      its variations. Clinical presentation, imaging findings, important
      neuroanatomical correlations, recurrence rates, and outcomes are discussed. 

PMID- 24289121
TI  - Extracranial ligation of ethmoidal arteries before resection of giant olfactory
      groove or planum sphenoidale meningiomas: 3 illustrative cases with a review of
      the literature on surgical techniques.
AB  - OBJECT: There are several surgical techniques for reducing blood loss-open
      surgical and endoscopic-prior to resection of giant anterior skull base
      meningiomas, especially when preoperative embolization is risky or not
      technically feasible. The authors present examples of an institutional experience
      using surgical ligation of the anterior and posterior ethmoidal arteries
      producing persistent tumor blush in partially embolized tumors. METHODS: The
      authors identified 12 patients who underwent extracranial surgical ligation of
      ethmoidal arteries through either a transcaruncular or a Lynch approach. Of
      these, 3 patients had giant olfactory groove or planum sphenoidale meningiomas.
      After approval from the institution privacy officer, the authors studied the
      medical records and imaging data of these 3 patients, with special attention to
      surgical technique and outcome. The variations of ethmoidal artery foramina
      pertaining to this surgical approach were studied using preserved human skulls
      from the Hamann-Todd Osteological Collection at the Museum of Natural History,
      Cleveland, Ohio. RESULTS: The extracranial ligation was performed successfully
      for control of the ethmoidal arteries prior to resection of hypervascular giant
      anterior skull base meningiomas. The surgical anatomy and landmarks for ethmoidal
      arteries were reviewed in anthropology specimens and available literature with
      reference to described surgical techniques. CONCLUSIONS: Extracranial surgical
      ligation of anterior, and often posterior, ethmoidal arteries prior to resection
      of large olfactory groove or planum sphenoidale meningiomas provides a safe and
      feasible option for control of these vessels prior to either open or endoscopic
      resection of nonembolized or partially embolized tumors.

PMID- 24289122
TI  - Patterns of recurrence after stereotactic radiosurgery for treatment of
      meningiomas.
AB  - OBJECT: The purpose of this study was to evaluate patterns of failure after
      stereotactic radiosurgery (SRS) for meningiomas and factors that may influence
      these outcomes. METHODS: Based on a retrospective chart review, 279 patients were
      treated with SRS for meningiomas between January 1999 and March 2011 at Wake
      Forest Baptist Health. Disease progression was determined using serial imaging,
      with a minimum follow-up of 6 months (median 34.2 months). RESULTS: The median
      margin dose was 12.0 Gy (range 8.8-20 Gy). Local control rates for WHO Grade I
      tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade
      II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and
      5 years, respectively. Tumors without pathological grading had local control
      rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local
      recurrences, 63.1% were classified as marginal (within 2 cm of treatment field).
      The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%,
      respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for
      Grade II/III tumors. Tumors without pathological grading had distant failure
      rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon
      analysis revealed that multifocal disease (p < 0.001) and high-grade histology
      (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence.
      Additionally, male sex was a significant predictor of distant recurrence (p =
      0.04). Multivariate analysis also showed that doses greater than or equal to 12
      Gy were associated with improved local control (p = 0.015). CONCLUSIONS: In this
      patient series, 12 Gy was the minimum sufficient margin dose for the treatment of
      meningiomas. Male sex is a risk factor for distant failure, whereas high-grade
      histology and multifocal disease are risk factors for local failure.

PMID- 24289123
TI  - Atypical meningiomas: is postoperative radiotherapy indicated?
AB  - OBJECT: The role of postoperative radiation therapy after surgery for atypical
      meningiomas remains controversial. In this retrospective cohort study, the
      authors examine the recurrence rates for atypical meningiomas after resection
      (with or without adjuvant radiotherapy) and identify which factors were
      associated with recurrence. METHODS: Of 90 patients with atypical meningiomas who
      underwent surgery between 1999 and 2009, 71 (79%) underwent gross-total resection
      (GTR) and 19 (21%) underwent subtotal resection (STR); 31 patients received
      adjuvant radiotherapy. All tumors were pathology-confirmed WHO Grade II atypical
      meningiomas. Univariate and multivariate analyses were performed to identify
      factors associated with recurrence-free survival. RESULTS: Among 90 patients, 17
      developed tumor recurrence (81% recurrence-free survival at 5 years). In the
      overall group, adjuvant radiotherapy reduced the recurrence rate to 9% from 19%
      at 5 years (p = 0.048). After STR, adjuvant radiotherapy significantly reduced
      recurrence from 91% to 20% (p = 0.0016). However, after GTR, adjuvant
      radiotherapy did not significantly reduce the recurrence rate (16.7% without
      radiation therapy vs 11.8% with radiation therapy) (p = 1.00). Five factors
      independently predictive of tumor recurrence included mitotic index, sheeting,
      necrosis, nonuse of radiation therapy, and STR. Further recursive partitioning
      analysis showed significant increases in risk for patients older than 55 years
      with mitoses and sheeting. CONCLUSIONS: Adjuvant radiotherapy was effective at
      lowering recurrence rates in patients after STR but delivered no significant
      improvement in patients after GTR. Given that rates after GTR were similar with
      or without adjuvant radiotherapy, close observation without postoperative
      radiation therapy may be a viable option for these patients. Patients older than
      55 years and those with mitoses noted during pathological examination had a
      significant risk of recurrence after GTR; for these patients, postoperative
      radiotherapy is recommended.

PMID- 24289124
TI  - The role of radiosurgery in the management of WHO Grade II and III intracranial
      meningiomas.
AB  - OBJECT: WHO Grade II and III intracranial meningiomas are uncommon, but they
      portend a significantly worse prognosis than their benign Grade I counterparts.
      The mainstay of current management is resection to obtain cytoreduction and
      histological tissue diagnosis. The timing and benefit of postoperative
      fractionated external beam radiation therapy and stereotactic radiosurgery remain
      controversial. The authors review the stereotactic radiosurgery outcomes for
      Grade II and III meningiomas. METHODS: A comprehensive literature search was
      performed using PubMed to identify all radiosurgery series reporting the
      treatment outcomes for Grade II and III meningiomas. Case reports and case series
      involving fewer than 10 patients were excluded. RESULTS: From 1998 to 2013, 19
      radiosurgery series were published in which 647 Grade II and III meningiomas were
      treated. Median tumor volumes were 2.2-14.6 cm(3). The median margin doses were
      14-21 Gy, although generally the margin doses for Grade II meningiomas were 16-20
      Gy and the margin doses for Grade III meningiomas were 18-22 Gy. The median 5
      year PFS was 59% for Grade II tumors and 13% for Grade III tumors, which may have
      been affected by patient age, prior radiation therapy, tumor volume, and
      radiosurgical dose and timing. The median complication rate following
      radiosurgery was 8%. CONCLUSIONS: The current data for radiosurgery suggest that
      it has a role in the management of residual or recurrent Grade II and III
      meningiomas. However, better studies are needed to fully define this role. Due to
      the relatively low prevalence of these tumors, it is unlikely that prospective
      studies will be feasible. As such, well-designed retrospective analyses may
      improve our understanding of the effect of radiosurgery on tumor recurrence and
      patient survival and the incidence and impact of treatment-induced complications.

PMID- 24289125
TI  - Controversies in the role of preoperative embolization in meningioma management.
AB  - The role of preoperative embolization in meningioma management remains
      controversial, even though 4 decades have passed since it was first described. It
      has been shown to offer benefits such as decreased blood loss and "softening of
      the tumor" during subsequent resection. However, the actual benefits remain
      unclear, and the potential harm of an additional procedure along with the cost of
      embolization have limited its use to a small proportion of the meningiomas
      treated. In this article the authors retrospectively reviewed their experience
      with preoperative embolization of meningiomas over the previous 6 years (March
      2007-March 2013). In addition, they performed a MEDLINE search using a
      combination of the terms "meningioma," "preoperative," and "embolization" to
      analyze the indications, embolizing agents, timing, and complications reported
      during preoperative embolization of meningiomas. In this retrospective review, 18
      cases (female/male ratio 12:6) were identified in which endovascular embolization
      was used prior to resection of an intracranial meningioma. Craniotomy for tumor
      resection was performed within 4 days after endovascular embolization in all
      cases, with an average time to surgery of 1.9 days. The average duration of
      surgery was 4 hours and 18 minutes, and the average blood loss was 574 ml, with a
      range of 300-1000 ml. Complications following endovascular therapy were
      identified in 3 (16.7%) of 18 cases, including one each of transient hemiparesis,
      permanent hemiparesis, and tumor swelling. The literature review returned 15
      articles consisting of a study population greater than 25 patients. No randomized
      controlled study was found. The use of small polyvinyl alcohol particles (45-150
      MUm) is more effective in preoperative devascularization than larger particles
      (150-250 MUm), but is criticized due to the higher risk of complications such as
      cranial nerve palsies and postprocedural hemorrhage. Time to surgery after
      embolization is inconsistently reported across the articles, and conclusions on
      the appropriate timing of surgery could not be drawn. The overall complication
      rate reported after treatment with preoperative meningioma embolization ranges
      from as high as 21% in some of the older literature to approximately 6% in recent
      literature describing treatment with newer embolization techniques. The evidence
      in the literature supporting the use of preoperative meningioma embolization is
      mainly from case series, and represents Level III evidence. Due to the lack of
      randomized controlled clinical trials, it is difficult to draw any significant
      conclusions on the overall usefulness of preoperative embolization during the
      management of meningiomas to consider it a standard practice. 

PMID- 24289126
TI  - Recent developments in chemotherapy for meningiomas: a review.
AB  - OBJECT: Currently, few medical options exist for refractory and
      atypical/anaplastic meningiomas. New developments in chemotherapeutic options for
      meningiomas have been explored over the past decade. The authors review these
      recent developments, with an emphasis on emerging avenues for therapy, clinical
      efficacy, and adverse effects. METHODS: A review of the literature was performed
      to identify any studies exploring recent medical and chemotherapeutic agents that
      have been or are currently being tested for meningiomas. RESULTS: from included
      preclinical and human clinical trials were reviewed and summarized. RESULTS:
      Current guidelines recommend only 3 drugs that can be used to treat patients with
      refractory and highgrade meningiomas: hydroxyurea, interferon-alpha 2B, and
      Sandostatin long-acting release. Recent developments in the medical treatment of
      meningiomas have been made across a variety of pharmacological classes, including
      cytotoxic agents, hormonal agents, immunomodulators, and targeted agents toward a
      variety of growth factors and their signaling cascades. Promising avenues of
      therapy that are being evaluated for efficacy and safety include antagonists of
      platelet-derived growth factor receptor, epidermal growth factor receptor,
      vascular endothelial growth factor receptor, and mammalian target of rapamycin.
      Because malignant transformation in meningiomas is likely to be mediated by
      numerous processes interacting via a complex matrix of signals, combination
      therapies affecting multiple molecular targets are currently being explored and
      hold significant promise as adjuvant therapy options. CONCLUSIONS: Improved
      understanding of the molecular mechanisms driving meningioma tumorigenesis and
      malignant transformation has resulted in the targeted development of more
      specific agents for chemotherapeutic intervention in patients with nonresectable,
      aggressive, and malignant meningiomas.

PMID- 24289127
TI  - Peritumoral brain edema in intracranial meningiomas: the emergence of vascular
      endothelial growth factor-directed therapy.
AB  - Meningioma is the second most common type of adult intracranial neoplasm. A
      substantial subset of patients present with peritumoral brain edema (PTBE), which
      can cause significant morbidity via mass effect, complicate surgical management,
      and impact the safety of stereotactic radiosurgery. Recent studies suggest a
      close relationship between vascular endothelial growth factor-A (VEGF-A)
      expression and PTBE development in meningiomas. The authors performed a
      systematic review of the literature on the pathogenesis of PTBE in meningiomas,
      the effectiveness of steroid therapy, the role played by VEGF-A, and the current
      clinical evidence for antiangiogenic therapy to treat peritumoral brain edema.
      Mounting evidence suggests VEGF-A is secreted directly by meningioma cells to
      induce angiogenesis and edemagenesis of tumoral as well as peritumoral brain
      tissue. The VEGF-A cascade results in recruitment of cerebral-pial vessels and
      disruption of the tumor-brain barrier, which appear to be requisite for VEGF-A to
      have an edemagenic effect. Results of preliminary clinical studies suggest VEGF
      directed therapy has modest activity against recurrent and progressive meningioma
      growth but can alleviate PTBE in some patients. A comprehensive understanding of
      the VEGF-A pathway and its modulators may hold the key to an effective
      therapeutic approach to treating PTBE associated with meningiomas. Further
      clinical trials with larger patient cohorts and longer follow-up periods are
      warranted to confirm the efficacy of VEGF-directed therapy. 

PMID- 24289128
TI  - Genomic and transcriptome analysis revealing an oncogenic functional module in
      meningiomas.
AB  - OBJECT: Meningiomas are among the most common primary adult brain tumors.
      Although typically benign, roughly 2%-5% display malignant pathological features.
      The key molecular pathways involved in malignant transformation remain to be
      determined. METHODS: Illumina expression microarrays were used to assess gene
      expression levels, and Illumina single-nucleotide polymorphism arrays were used
      to identify copy number variants in benign, atypical, and malignant meningiomas
      (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression
      data sets generated on Affymetrix microarrays (n = 68, including 6 malignant
      ones; n = 56, including 3 malignant ones). A weighted gene coexpression network
      approach was used to identify coexpression modules associated with malignancy.
      RESULTS: At the genomic level, malignant meningiomas had more chromosomal losses
      than atypical and benign meningiomas, with average length of 528, 203, and 34
      megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one
      of the primary chromosomal level abnormalities in all subtypes of meningiomas. At
      the transcriptome level, the authors identified 23 coexpression modules from the
      weighted gene coexpression network. Gene functional enrichment analysis
      highlighted a module with 356 genes that was highly related to tumorigenesis.
      Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were
      oncogenic in other cancers such as leukemia. A putative meningioma tumor
      suppressor MN1 was also identified in this module with differential expression
      between malignant and benign meningiomas. CONCLUSIONS: The authors' genomic and
      transcriptome analysis of meningiomas provides novel insights into the molecular
      pathways involved in malignant transformation of meningiomas, with implications
      for molecular heterogeneity of the disease.

PMID- 24289129
TI  - Current standing and frontiers of gene therapy for meningiomas.
AB  - Meningiomas are among the most common intracranial tumors. The treatment of
      choice for these lesions is complete resection, but in 50% of cases it is not
      achieved due to tumor location and/or surgical morbidities. Moreover, benign
      meningiomas have high recurrence rates of up to 32% in long-term follow-up.
      Molecular analyses have begun to uncover the genetics behind meningiomas, giving
      rise to potential genetics-based treatments, including gene therapy. The authors
      performed a literature review on the most relevant genes associated with
      meningiomas and both current and potential gene therapy strategies to treat these
      tumors. Wild-type NF2 gene insertion, oncolytic viruses, and transfer of
      silencing RNA have all shown promising results both in vitro and in mice. These
      strategies have decreased meningioma cell growth, proliferation, and
      angiogenesis. However, no clinical trial has been done to date. Future research
      and trials in gene insertion, selective inhibition of oncogenes, and the use of
      oncolytic viruses, among other potential treatment approaches, may shape the
      future of meningioma management. 

PMID- 24289130
TI  - A review of epigenetic and gene expression alterations associated with
      intracranial meningiomas.
AB  - OBJECT: A more comprehensive understanding of the epigenetic abnormalities
      associated with meningioma tumorigenesis, growth, and invasion may provide useful
      targets for molecular classification and development of targeted therapies for
      meningiomas. METHODS: The authors performed a review of the current literature to
      identify the epigenetic modifications associated with the formation and/or
      progression of meningiomas. RESULTS: Several epigenomic alterations, mainly
      pertaining to DNA methylation, have been associated with meningiomas.
      Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2
      (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with
      the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2,
      and TGF-beta epigenetic modifications allow either upregulation or downregulation
      of critical pathways for meningioma development, progression, and recurrence.
      CONCLUSIONS: Genome-wide methylation profiling demonstrated that global
      hypomethylation correlates with tumor grades and severity. Identification of
      additional epigenetic changes, such as histone modification and higher-order
      chromosomal structure, may allow for a more thorough understanding of
      tumorigenesis and enable future individualized treatment strategies for
      meningiomas.

PMID- 24289131
TI  - Endoscopic extended transsphenoidal resection of tuberculum sellae meningiomas:
      nuances of neurosurgical technique.
AB  - Over the past decade, advances in endoscopic microsurgical techniques have
      resulted in an increasingly aggressive endonasal approach to tumors of the
      midline skull base. Meningiomas of the tuberculum sellae are often closely
      associated with cerebrovascular structures, and their removal has traditionally
      required a transcranial approach. An endonasal approach offers many advantages,
      including early tumor devascularization and tumor debulking (without manipulation
      of the optic apparatus), direct access to the medial optic canal, and a minimal
      access corridor. Although recent articles have focused on techniques for reaching
      and approaching the area of the pathology (how to get there), the authors of this
      report discuss the technical nuances of endoscopic microsurgery when the operator
      is already "there." They describe their 6-step technique for endoscopic skull
      base bone removal, tumor dissection/resection, and closure. They also augment
      their description with elaborate illustrations. 

PMID- 24289132
TI  - Technical nuances in the management of tuberculum sellae and diaphragma sellae
      meningiomas.
AB  - OBJECT: Tuberculum sellae meningiomas (TSMs) and diaphragma sellae meningiomas
      (DSMs) are challenging lesions to treat due to their proximity to neurovascular
      structures. METHODS: The authors reviewed the medical records of patients who
      underwent surgical excision of TSMs and DSMs from 1990 to 2013. They also
      describe the technical strategies used to minimize injury to the optic apparatus,
      vascular structures, and pituitary stalk. RESULTS: Twenty-four patients with TSM
      and 6 patients with DSM were included in the study. Seventy percent of the tumors
      were large (>= 5 cm). The pterional approach was employed in most cases. Optic
      canal involvement was observed in 4 patients. Twenty-one patients (70%) had
      visual dysfunction before surgery. At follow-up (median 18 months), visual
      improvement was noted in 10 (47.6%) of 21 patients. Gross-total excision was
      achieved in 22 patients (91.6%) with TSM and 5 (83.3%) with DSM. At last follow
      up, 28 patients (93.3%) had a Glasgow Outcome Scale score of 5. There were no
      deaths in this series. CONCLUSIONS: Tuberculum and diaphragma sellae meningiomas
      present a unique subset of tumors due to their location. They can be safely
      excised with minimal morbidity and mortality using microsurgical techniques.
      Attention to technical details during surgery leads to greater respectability and
      superior visual outcome.

PMID- 24289133
TI  - The treatment of cavernous sinus meningiomas: evolution of a modern approach.
AB  - Cavernous sinus meningiomas (CSMs) are challenging lesions for the skull base
      neurosurgeon to manage given their close association with cranial nerves II-VI
      and the internal carotid artery. In the 1980s and early 1990s, with advancements
      in microsurgical techniques, increasing knowledge of the relevant microsurgical
      neuroanatomy, and the advent of advanced skull base surgical approaches, the
      treatment of CSMs involved attempts at gross-total resection (GTR). Initial
      fervor for a surgical cure waned, however, as skull base neurosurgeons
      demonstrated the limits of complete resection in this region, the ongoing issue
      of potential tumor recurrences, and the unacceptably high cranial nerve and
      vascular morbidity associated with this strategy. The advent of radiosurgery and
      its documented success for tumor growth control and limited morbidity in
      cavernous lesions has helped to shift the treatment goals for CSMs from GTR to
      tumor control and symptom relief while minimizing treatment- and lesion
      associated morbidity. The authors review the relevant microanatomy of the
      cavernous sinus with anatomical and radiographic correlates, as well as the
      various treatment options. A modernized, multimodality treatment algorithm to
      guide management of these lesions is proposed. 

PMID- 24289134
TI  - Management of meningiomas involving the transverse or sigmoid sinus.
AB  - Meningiomas that invade the transverse or sigmoid sinuses are uncommon tumors
      that are challenging to treat surgically. Although the risk of recurrence is
      associated with the extent of resection, complete removal of meningiomas in these
      locations must be balanced with avoidance of venous outflow obstruction, which
      could cause venous infarction and significant neurological consequences. When a
      meningioma occludes a venous sinus completely, gross-total resection of the
      intravascular portion is commonly performed. When the tumor invades but does not
      completely obliterate a major venous sinus, however, opinions differ on whether
      to accept a subtotal resection or to open the sinus, perform a complete
      resection, and reconstruct the venous outflow tract. In this paper, the authors
      review the different strategies used to treat these lesions and provide
      illustrative case examples. 

PMID- 24289135
TI  - Meningiomas.

PMID- 24289137
TI  - Distinctive patterns of epigenetic marks are associated with promoter regions of
      mouse LINE-1 and LTR retrotransposons.
AB  - BACKGROUND: The long terminal repeat (LTR) retrotransposons and the non-LTR
      retrotransposons (LINE-1 or L1) make up more than one-third of the mouse genome.
      Because of their abundance, the retrotransposons are the major players in genomic
      structure and function. While much attention has been focused on the biology of
      retrotransposons, little is known about the chromatin structure of these elements
      or the potential role of epigenetic marks on the regulation of retrotransposon
      expression. FINDINGS: Using sequential chromatin immunoprecipitation analysis, we
      analyzed the cohabitation of several post-translational histone modifications in
      the promoter regions of mouse L1 and LTR retrotransposons. We show here that the
      variant histone H2A.Z selectively present in L1 promoters. Notably, H2A.Z and
      trimethylated histone H3 (H3K9me3) co-localize in the same genomic location of
      the L1 promoter along with heterochromatin-binding protein HP1alpha. In contrast,
      MmERV and intracisternal A-particle (IAP) classes of LTR promoters are enriched
      with core histone H2A and heterochromatic trimethylated histone H4 (H4K20me3).
      These distinctive patterns of chromatin modifications are relatively consistent
      irrespective of cell type. CONCLUSIONS: Chromatin structure regulates the
      expression of retrotransposons. LINE-1 elements are associated with H2A.Z and
      HP1alpha-containing constitutive heterochromatin, while the LTR elements are
      enriched with H2A and the H4K20me3-type of facultative heterochromatin. Our
      findings demonstrate that different epigenetic mechanisms operate in the mouse
      genome to silence different classes of retrotransposons.

PMID- 24289136
TI  - Reproducibility and accuracy of optic nerve sheath diameter assessment using
      ultrasound compared to magnetic resonance imaging.
AB  - BACKGROUND: Quantification of the optic nerve sheath diameter (ONSD) by
      transbulbar sonography is a promising non-invasive technique for the detection of
      altered intracranial pressure. In order to establish this method as follow-up
      tool in diseases with intracranial hyper- or hypotension scan-rescan
      reproducibility and accuracy need to be systematically investigated. METHODS: The
      right ONSD of 15 healthy volunteers (mean age 24.5 +/- 0.8 years) were measured
      by both transbulbar sonography (9 - 3 MHz) and 3 Tesla MRI (half-Fourier
      acquisition single-shot turbo spin-echo sequences, HASTE) 3 and 5 mm behind
      papilla. All volunteers underwent repeated ultrasound and MRI examinations in
      order to assess scan-rescan reproducibility and accuracy. Moreover, inter- and
      intra-observer variabilities were calculated for both techniques. RESULTS: Scan
      rescan reproducibility was robust for ONSD quantification by sonography and MRI
      at both depths (r > 0.75, p <= 0.001, mean differences < 2%). Comparing
      ultrasound- and MRI-derived ONSD values, we found acceptable agreement between
      both methods for measurements at a depth of 3 mm (r = 0.72, p = 0.002, mean
      difference < 5%). Further analyses revealed good inter- and intra-observer
      reliability for sonographic measurements 3 mm behind the papilla and for MRI at 3
      and 5 mm (r > 0.82, p < 0.001, mean differences < 5%). CONCLUSIONS: Sonographic
      ONSD quantification 3 mm behind the papilla can be performed with good
      reproducibility, measurement accuracy and observer agreement. Thus, our findings
      emphasize the feasibility of this technique as a non-invasive bedside tool for
      longitudinal ONSD measurements.

PMID- 24289138
TI  - Severe hematuria after transurethral electrocoagulation in a patient with an
      arteriovesical fistula.
AB  - BACKGROUND: Arteriovesical fistulas are extremely rare. Only eleven cases were
      previously reported in the literature. They can occur iatrogenically,
      traumatically or spontaneously. CASE PRESENTATION: We report an unusual case of a
      62-year-old woman with arteriovesical fistula that developed fatal hematuria
      after transurethral electrocoagulation. Computed tomography (CT) and selective
      angiography revealed a pseudoaneurysm of the right superior vesical artery with
      arteriovesical fistula formation, which was managed by transarterial
      embolization. CONCLUSIONS: Contrast enhanced CT or CT angiography should be
      performed when a pulsatile hemorrhage is revealed during cystoscopy. Therapeutic
      vesical arterial embolization should be considered as a safe and effective
      procedure for arteriovesical fistulas. Transurethral electrocoagulation may cause
      severe hematuria for pulsatile bladder bleeding in patients with pelvic vascular
      malformation.

PMID- 24289139
TI  - Paramagnetic metal ions in pulsed ESR distance distribution measurements.
AB  - The use of pulsed electron spin resonance (ESR) to measure interspin distance
      distributions has advanced biophysical research. The three major techniques that
      use pulsed ESR are relaxation rate based distance measurements, double quantum
      coherence (DQC), and double electron electron resonance (DEER). Among these
      methods, the DEER technique has become particularly popular largely because it is
      easy to implement on commercial instruments and because programs are available to
      analyze experimental data. Researchers have widely used DEER to measure the
      structure and conformational dynamics of molecules labeled with the
      methanethiosulfonate spin label (MTSSL). Recently, researchers have exploited
      endogenously bound paramagnetic metal ions as spin probes as a way to determine
      structural constraints in metalloproteins. In this context Cu(2+) has served as a
      useful paramagnetic metal probe at X-band for DEER based distance measurements.
      Sample preparation is simple, and a coordinated-Cu(2+) ion offers limited spatial
      flexibility, making it an attractive probe for DEER experiments. On the other
      hand, Cu(2+) has a broad absorption ESR spectrum at low temperature, which leads
      to two potential complications. First, the Cu(2+)-based DEER time domain data has
      lower signal to noise ratio compared with MTSSL. Second, accurate distance
      distribution analysis often requires high-quality experimental data at different
      external magnetic fields or with different frequency offsets. In this Account, we
      summarize characteristics of Cu(2+)-based DEER distance distribution measurements
      and data analysis methods. We highlight a novel application of such measurements
      in a protein-DNA complex to identify the metal ion binding site and to elucidate
      its chemical mechanism of function. We also survey the progress of research on
      other metal ions in high frequency DEER experiments. 

PMID- 24289140
TI  - Evaluation of antibacterial and anti-inflammatory activities of less polar
      ginsenosides produced from polar ginsenosides by heat-transformation.
AB  - Ginsenosides are the major active constituents in both white and red American
      ginseng (AG), and their pharmacological effects on central nervous,
      cardiovascular, and endocrine systems have been well elucidated. However, the
      anti-Propionibacterium acnes (P. acnes) activity of them is still unknown. In
      this study, 5 ginsenosides enriched fractions were obtained from the total
      ginsenosides extract of AG roots (TAG) by resin adsorption and heat
      transformation. Resin purification decreased the total polyphenol (TP) content in
      the fractions. However, heat treatment increased the TP content and induced
      extensive conversion of the polar ginsenosides (Rg1, Re, Rb1, Rc, Rb2, Rd, and
      Gyp XVII) to less polar compounds (Rg2, Rg3, Rg6/F4, Rs3, and Rg5/Rk1). Only the
      heat-treated fraction from 65% methanol elution of the HP-20 column (HPHF) showed
      antibacterial activity against P. acnes (ATCC11827, MIC, 128 MUg/mL; ATCC6919
      MIC, 64 MUg/mL), S. epidermidis (MIC, 4100 MUg/mL) and S. aureus (MIC, 15000
      MUg/mL). In the anti-inflammatory activity assay, 10 MUg/mL of HPHF significantly
      (P < 0.05) inhibited NO production in LPS-stimulated RAW264.7 cells. These
      results suggest that less polar ginsenosides enriched fraction HPHF obtained from
      AG might be useful to develop new types of antibacterial substances and new skin
      care cosmetics for acne prevention and therapy. 

PMID- 24289141
TI  - Switching from oral risperidone to flexibly dosed oral paliperidone extended
      release: core symptoms, satisfaction, and quality of life in patients with stable
      but symptomatic schizophrenia: the RISPALI study.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate the effects of
      switching from oral risperidone to flexibly dosed oral paliperidone extended
      release (ER) in Brazilian adults with schizophrenia because of lack of efficacy,
      intolerability, or nonadherence after a minimum trial of 30 days on adequate
      (labeled) doses of oral risperidone, according to individual clinical judgment.
      RESEARCH DESIGN AND METHODS: Subjects with Positive and Negative Syndrome Scale
      total scores above 78, and/or intolerable adverse effects, with risperidone
      received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52
      (extension phase) weeks. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov
      identifier: NCT01010776. RESULTS: The intent-to-treat (efficacy) populations
      comprised 213 subjects in the main phase and 159 in the extension phase. Of 213
      subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from
      risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%)
      because of tolerability issues, according to individual clinical judgment.
      Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy
      endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4
      weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints,
      function improved from baseline to the first post-baseline visit (week 4) and
      remained significantly improved compared to baseline at each visit for
      paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported
      herein mainly for 26 and 52 weeks compared to baseline. Significant improvements
      from baseline were observed for the Positive and Negative Syndrome Scale total
      score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and
      personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER
      also significantly improved health-related quality of life (Short-Form 36) from
      baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks
      and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly
      improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh
      Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity
      (Clinical Global Impression-Severity; p < 0.0001 at each visit vs. baseline).
      Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of
      subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the
      extension phase); increased body weight (10.7% and 12.6%, respectively); and
      anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or
      moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment
      or interruption; and 3) decreased in frequency from the main to the extension
      phase. CONCLUSIONS: Oral paliperidone ER is a rational treatment alternative for
      patients with schizophrenia whose antipsychotic regimens are switched because of
      unsuccessful treatment with oral risperidone according to individual clinical
      judgment. Study limitations included the open-label study design, lack of
      placebo, and use of subjective clinical judgment to determine lack of efficacy,
      intolerability, or nonadherence with oral risperidone.

PMID- 24289142
TI  - Haemoglobin levels for population from Gambo, a rural area of Ethiopia, and their
      association with anaemia and malaria.
AB  - BACKGROUND: Knowledge of appropriate reference intervals is critical not only to
      provide optimal clinical care, but also to enrol populations in medical research.
      The aim of this study was to generate normal ranges of laboratory values for
      haemoglobin among healthy Ethiopian adults and children and to determine if
      anaemia is a possible indicator of malaria in women and children in this area of
      Ethiopia. METHODS: This study was carried out from January 2008 to May 2010. The
      reference sample population with malaria-negative consisted of 454 individuals,
      divided women, men and children. The malaria-infected sample population consisted
      of 117 individuals. The reference ranges were based on the guidelines from the
      Clinical and Laboratory Standards Institute. Haemoglobin concentration was
      determined by Hemo-Control EKF Diagnostic Analyser on whole blood. Testing for
      malaria-positive and negative infection was done by microscopy and by PCR.
      RESULTS: The lower limits for adult haemoglobin range obtained from this
      population were slightly higher than those derived from other African
      populations, but were equal to those established by other studies in Ethiopia and
      the World Health Organization (WHO). Regarding children, the minimum values were
      lower than those obtained from different African populations and those
      established by WHO. The malaria-negative group had anaemia in 35.6% of cases and
      in the malaria-positive group in 70.9%. There was a stronger, statistically
      significant association between anaemia and malaria-positive samples than between
      anaemia and malaria-negative samples in women and both groups of children.
      CONCLUSIONS: The results from this study are a contribution in the definition of
      the haemoglobin parameters in African populations, which could be taken as
      standards for interpretation of laboratory results. The haemoglobin indices in
      adults from Gambo tended to be higher than other African populations and in
      children were lower than other studies in Africa. The results also suggest that
      anaemia is not useful as a supportive diagnostic criterion to monitor and
      evaluate malaria in women and children from Ethiopia, because a 29.1% of malaria
      cases will be not detected, because of not having anaemia.

PMID- 24289143
TI  - QM/MM calculations reveal the different nature of the interaction of two
      carborane-based sulfamide inhibitors of human carbonic anhydrase II.
AB  - The crystal structures of two novel carborane-sulfamide inhibitors in the complex
      with human carbonic anhydrase II (hCAII) have been studied using QM/MM
      calculations. Even though both complexes possess the strongly interacting
      sulfamide...zinc ion motif, the calculations have revealed the different nature
      of binding of the carborane parts of the inhibitors. The neutral closo-carborane
      cage was bound to hCAII mainly via dispersion interactions and formed only very
      weak dihydrogen bonds. On the contrary, the monoanionic nido cage interacted with
      the protein mainly via electrostatic interactions. It formed short and strong
      dihydrogen bonds (stabilization of up to 4.2 kcal/mol; H...H distances of 1.7 A)
      with the polar hydrogen of protein NH2 groups. This type of binding is unique
      among all of the classical organic and inorganic inhibitors of hCAII. Virtual
      glycine scanning allowed us to identify the amino-acid side chains, which made
      important contributions to ligand-binding energies. In summary, using QM/MM
      calculations, we have provided a detailed understanding of the differences
      between the interactions of two carborane sulfamides, identified the amino acids
      of hCAII with which they interact, and thus paved the way for the computer-aided
      rational design of selective boron-cluster-containing hCAII inhibitors. 

PMID- 24289144
TI  - Bayesian analysis of time-series data under case-crossover designs: posterior
      equivalence and inference.
AB  - Case-crossover designs are widely used to study short-term exposure effects on
      the risk of acute adverse health events. While the frequentist literature on this
      topic is vast, there is no Bayesian work in this general area. The contribution
      of this paper is twofold. First, the paper establishes Bayesian equivalence
      results that require characterization of the set of priors under which the
      posterior distributions of the risk ratio parameters based on a case-crossover
      and time-series analysis are identical. Second, the paper studies inferential
      issues under case-crossover designs in a Bayesian framework. Traditionally, a
      conditional logistic regression is used for inference on risk-ratio parameters in
      case-crossover studies. We consider instead a more general full likelihood-based
      approach which makes less restrictive assumptions on the risk functions.
      Formulation of a full likelihood leads to growth in the number of parameters
      proportional to the sample size. We propose a semi-parametric Bayesian approach
      using a Dirichlet process prior to handle the random nuisance parameters that
      appear in a full likelihood formulation. We carry out a simulation study to
      compare the Bayesian methods based on full and conditional likelihood with the
      standard frequentist approaches for case-crossover and time-series analysis. The
      proposed methods are illustrated through the Detroit Asthma Morbidity, Air
      Quality and Traffic study, which examines the association between acute asthma
      risk and ambient air pollutant concentrations. 

PMID- 24289145
TI  - Ectomycorrhizal fungal traits reflect environmental conditions along a coastal
      California edaphic gradient.
AB  - Multispecies mutualisms, such as the association between trees and
      ectomycorrhizal fungi, are often shaped by environmental context. Here, we
      explored the functional mechanisms underlying this environmental filtering. Using
      a single population of Pinus muricata (Bishop pine) growing along a strong
      edaphic gradient, we examined how environmental stress affected ectomycorrhizal
      fungi. The gradient spans c. 400000 years of soil age, and reduced nutrient
      availability and increased water stress dwarf trees on older sites. Fungal
      community composition shifted with nutrient and water availability and with the
      stature of the P. muricata host trees. Not only did pygmy trees host a
      taxonomically different fungal subset as compared to nonpygmy trees, but
      associated fungal communities also differed in life history strategies: trees in
      more stressful conditions hosted fungi with more carbon-intensive foraging
      strategies. Our results indicate a link between environmental controls of host
      nutritional status and turnover in the ectomycorrhizal fungal community. The
      transition to more energy-intensive strategies under nutrient stress may allow
      for close recycling of recalcitrant nutrient pools within the root zone and
      facilitate transport of nutrients and water over long distances. These results
      highlight the value of life history data to understanding the mechanistic
      underpinnings of species distributions.

PMID- 24289147
TI  - Sequence and organization of complete mitochondrial genome of the firefly,
      Aquatica leii (Coleoptera: Lampyridae).
AB  - The firefly Aquatica leii (Coleoptera: Lampyridae) is widely distributed in
      China. In this study, we sequenced and characterized the first complete
      mitochondrial genome of the firefly from the subfamily Luciolinae. The circular
      genome of 16,856 bp in length contains 13 protein-coding genes, 22 transfer RNA
      genes, 2 ribosomal RNA genes and a non-coding AT-rich region. Overall base
      composition of the genome is 42.28% A, 34.80% T, 13.91% C and 9.01% G, with an AT
      bias of 77.08%. All protein-coding genes start with an ATN codon, and terminate
      with the typical stop codon TAA, TAG or a single T. The non-coding AT-rich region
      is unusually long (2239 bp), containing six 113 bp tandem repeats and a
      microsatellite-like (TA)7 element. The genome sequence is useful for studying the
      evolution of sexual signaling and many ecological specializations in fireflies.

PMID- 24289146
TI  - Inter- and intra-laboratory comparison of a multibiodosimetric approach to triage
      in a simulated, large scale radiation emergency.
AB  - PURPOSE: The European Union's Seventh Framework Programme-funded project 'Multi
      disciplinary biodosimetric tools to manage high scale radiological casualties'
      (MULTIBIODOSE) has developed a multiparametric approach to radiation
      biodosimetry, with a particular emphasis on triage of large numbers of
      potentially exposed individuals following accidental exposures. In November 2012,
      an emergency exercise took place which tested the capabilities of the
      MULTIBIODOSE project partners. The exercise described here had a dual purpose:
      Intercomparison of (i) three biodosimetric assays, and (ii) the capabilities of
      the seven laboratories, with regards to provision of triage status for suspected
      radiation exposed individuals. MATERIALS AND METHODS: Three biological dosimetry
      tools - the dicentric, micronucleus and gamma-H2AX (the phosphorylated form of
      member X of histone H2A, in response to DNA double-strand breaks) foci assays -
      were tested, in addition to provision of the triage status results (low exposure:
      < 1 Gy; medium exposure: 1-2 Gy; high exposure: > 2 Gy) by the MULTIBIODOSE
      software. The exercise was run in two modes: An initial triage categorisation of
      samples (based on the first dose estimates for each assay received from each
      laboratory) followed by collation of the full set of estimated doses (all the
      results from all modes of each assay carried out by the participating
      laboratories) calculated using as many modes of operation as possible of the
      different assays developed during the project. Simulated acute whole body and
      partial body exposures were included. RESULTS: The results of the initial triage
      categorisation and the full comparison of assays and methods within and between
      laboratories are presented here. CONCLUSIONS: The data demonstrate that the
      MULTIBIODOSE approach of applying multiparametric tools to radiation emergencies
      is valid and effective.

PMID- 24289148
TI  - The complete mitochondrial genome sequence of Chinese lizard gudgeon (Saurogobio
      dabryi).
AB  - The complete mitochondrial genome of Saurogobio dabryi is 16,604 bp in length
      with 55.88% AT content, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA
      genes, and 1 control region. The termination-associated sequence and six
      conserved sequence blocks were also identified. Compared all protein-coding genes
      and whole genome sequence with four species, Saurogobio dabryi has higher
      similarity with Gobio gobio than others. The mitogenome sequence of Saurogobio
      dabryi would play an important role in population structure and conservation
      genetic studies. 

PMID- 24289150
TI  - The puzzled low prevalence of atopic dermatitis in kindergarten children in
      Romania.

PMID- 24289149
TI  - PCR detects bands consistent with the expression of receptors associated with
      pruritus in canine dorsal root ganglia.
AB  - BACKGROUND: Various mediators are involved in the induction of itch, i.e.
      pruritus; however, the in vivo pharmacology of pruritus seems to be different in
      distinct species, and little is known about receptors that are involved in the
      induction of itch in dogs. The species differences in the mediation of pruritus
      might be explained by species differences in receptor expression in the sensory
      nerves, including the dorsal root ganglia (DRG). HYPOTHESIS/OBJECTIVES: The aim
      of the study was to analyse the expression of receptors for various mediators of
      pruritus in canine DRG. METHODS: Dorsal root ganglia of 14 dogs, which were
      euthanized for reasons not related to this study, were analysed. Multiple DRG per
      dog were dissected and, after homogenization of the DRG tissues, total RNA was
      isolated, reverse transcribed to complementary DNA and amplified with custom
      synthesized primers. RESULTS: The following receptors were found in canine DRG:
      transient receptor potential cation channel subfamily V member 1, tachykinin
      receptor 1, Toll-like receptor 7, endothelin receptor type A, opioid receptors
      MU1 and kappa1, histamine H1 -H4 receptors and the interleukin-31 receptor
      complex. CONCLUSIONS AND CLINICAL IMPORTANCE: PCR analysis detected bands
      consistent with the expression of receptors associated with pruritus in canine
      DRG.

PMID- 24289151
TI  - Association between neighborhood deprivation and fruits and vegetables
      consumption and leisure-time physical activity: a cross-sectional multilevel
      analysis.
AB  - BACKGROUND: Most studies of the association between neighborhood socioeconomic
      deprivation and individual lifestyles leading to cardiovascular disease focused
      on a single cardiovascular risk factor. The concomitant assessment of more than
      one risk factor may provide clues to specific mechanisms linking neighborhood
      disadvantage to individual lifestyles. We investigated the association of
      neighborhood deprivation with fruits and vegetables consumption and leisure-time
      physical activity in adults living in an urban center in Portugal. METHODS: In
      1999-2003, we assembled a random sample of 2081 adult residents in the city of
      Porto. Data on sociodemographic characteristics were collected by trained
      interviewers using structured questionnaires. Fruits and vegetables consumption
      was estimated using a validated 82-item semiquantitative food frequency
      questionnaire covering the previous year and expressed in portions per day.
      Physical activity was evaluated using a questionnaire exploring leisure-time
      activities over the previous year and expressed in metabolic equivalents
      (MET).minute/day. Self-reported address was used to place individuals in
      neighborhoods. Neighborhoods' socioeconomic characterization was based on
      aggregated data at the census block level provided by the 2001 National Census.
      Latent class analysis models were used to identify three discrete socioeconomic
      classes of neighborhoods. Random effects models with random intercepts at the
      neighborhood level were used to explore clustering and contextual effects of
      neighborhood deprivation on each of the outcomes. RESULTS: We found evidence of
      neighborhood clustering of fruits and vegetables consumption and leisure-time
      physical activity that persisted after adjustment for neighborhood deprivation
      only among women. Women living in the most deprived neighborhoods presented a
      consumption increase of 0.43 (95% CI: -0.033 to 0.89) portions of fruits and
      vegetables per day and a decrease in leisure-time physical activity of 47.8 (95%
      CI: -91.8 to 1.41) MET.minute/day, when compared to those living in the most
      affluent neighborhoods. Among men, no contextual neighborhood deprivation effects
      were observed. CONCLUSION: Overall, neighborhood deprivation had a small effect
      on the consumption of fruits and vegetables and leisure-time physical activity.
      Neighborhood factors other than socioeconomic deprivation may still impact on the
      studied outcomes among women. This study provides relevant information for the
      design of interventions directed to neighborhood characteristics in the
      prevention of cardiovascular diseases.

PMID- 24289153
TI  - Habits, rituals, and addiction: an inquiry into substance abuse in older persons.
AB  - Older people enter the final phases of their lives with well-established habits
      and rituals, some of which might be or become substance abuse. This inquiry
      focused on the relationship between habits, rituals, and the compulsive addictive
      behaviours evident in older persons' substance abuse. Habits and rituals,
      examined as adaptive and limiting functions in older persons, revealed changes in
      autonomy, social inclusion, and emotional responses to such changes as older
      persons experience declining energy reserves and physical debilities. Older
      persons' ebbing sense of control and passionate responses to change illustrate
      the perennial struggle between the will and emotions when habits and rituals
      transform to compulsive addictive behaviours. Two concepts, germane to this
      struggle both in older persons' addictive behaviours and nurses' response,
      emerged from this inquiry: temperance, a balance between the will's freely chosen
      actions and passionate desire, and discipline, the means to achieve such balance.
      The focused attention demanded in discipline can be realized in spiritual
      exercises and daily care of the soul. Disciplined actions engage the older
      persons' imaginative capacities to manage and abandon the self in goals
      consistent with end-of-life issues: meaningful fulfillment of human potential and
      the need for daily joy and pleasure in living the final years. 

PMID- 24289152
TI  - Platelet-activating factor downregulates the expression of liver X receptor-alpha
      and its target genes in human neutrophils.
AB  - Liver X receptors (LXRs) are ligand-activated members of the nuclear receptor
      superfamily that regulate the expression of genes involved in lipid metabolism
      and inflammation, although their role in inflammation and immunity is less well
      known. It has been reported that oxysterols/LXRs may act as anti-inflammatory
      molecules, although opposite actions have also been reported. In this study, we
      investigated the effect of platelet-activating factor (PAF), a proinflammatory
      molecule, on LXRalpha signalling in human neutrophils. We found that PAF exerted
      an inhibitory effect on mRNA expression of TO901317-induced LXRalpha, ATP-binding
      cassette transporter A1, ATP-binding cassette transporter G1, and sterol response
      element binding protein 1c. This negative action was mediated by the PAF
      receptor, and was dependent on the release of reactive oxygen species elicited by
      PAF, as it was enhanced by pro-oxidant treatment and reversed by antioxidants.
      Current data also support the idea that PAF induces phosphorylation of the
      LXRalpha molecule in an extracellular signal-regulated kinase 1/2-mediated
      fashion. These results suggest that a possible mechanism by which PAF exerts its
      proinflammatory effect is through the downregulation of LXRalpha and its related
      genes, which supports the notion that LXRalpha ligands exert a modulatory role in
      the neutrophil-mediated inflammatory response.

PMID- 24289154
TI  - Special issue from the 20th International Symposium on Alcohol Fuels (ISAF 2013):
      alcohol fuels enabling sustainable future development.
AB  - This Editorial introduces a special issue from the 20th International Symposium
      on Alcohol Fuels (ISAF 2013) on alcohol fuels enabling sustainable future
      development. 

PMID- 24289155
TI  - Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity
      in patients with compensated chronic hepatitis B.
AB  - BACKGROUND AND AIM: Due to known limitations of liver biopsy, reliable non
      invasive serum biomarkers for chronic liver diseases are needed. We performed
      serum peptidomics for such investigation in compensated chronic hepatitis B (CHB)
      patients. METHODS: Liquid chromatography combined with tandem mass spectrometry
      (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40
      CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification
      from differentially expressed peptides in a validation set of sera from 86 CHB
      patients was done with multiple reaction monitoring (MRM). RESULTS: 21
      differentially represented peptide peaks were found through LC-MS/MS. Ion pairs
      generated from eleven of these peptides (m/z < 800) were quantified by MRM.
      Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7,
      459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase
      (DAK) fragment, decreased from mild to advanced stages of fibrosis or
      inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of
      five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus
      S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation
      grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0
      2). The diagnostic power of these models provides improved sensitivity and
      specificity for predicting disease progression as compared to aspartate
      aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum
      DAK protein. CONCLUSIONS: The peptide fragment (m/z 520.3) of DAK is a promising
      biomarker to guide timing of antiviral treatment and to avoid liver biopsy in
      compensated CHB patients.

PMID- 24289156
TI  - B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis
      and subsequent infections in ICU patients.
AB  - INTRODUCTION: Sepsis is a deadly inflammatory condition that often leads to an
      immune suppressed state; however, the events leading to this state remain poorly
      understood. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor
      shown to effectively inhibit CD4+ T-cell function. Therefore, our objectives were
      to determine: 1) if lymphocyte BTLA expression was altered in critically ill
      patients and experimentally induced septic mice, 2) whether augmented CD4+ T-cell
      BTLA expression was associated with poor septic patient outcomes, and 3) if BTLA
      expression affected the CD4+ T-cell apoptotic cell loss observed in the lymphoid
      organs of septic mice. METHODS: Changes in CD4+ lymphocyte BTLA expression were
      compared with morbid event development in critically ill ICU patients (11 septic
      and 28 systemic inflammatory response syndrome subjects). Wild type and BTLA gene
      deficient mice were utilized to evaluate the expression and role of BTLA in
      septic lymphocyte apoptotic cell loss. RESULTS: The observed septic ICU patients
      had a significantly higher percentage of peripheral blood BTLA+ CD4+ lymphocytes
      compared with critically ill non-septic individuals. Moreover, the non-septic
      patients with CD4+ T-cells that were greater than 80% BTLA+  were more
      susceptible to developing nosocomial infections. Additionally, in general,
      critically ill patients with CD4+ T-cells that were greater than 80% BTLA+  had
      longer hospital stays. Comparatively, circulating CD4+ T-cell and B-cell BTLA
      expression increased in septic mice, which associated with the increased septic
      loss of these cells. Finally, the loss of these cells and cellular apoptosis
      induction in primary and secondary lymphoid organs were reversed in BTLA
      deficient mice. CONCLUSIONS: An increased BTLA+ CD4+ lymphocyte frequency in the
      observed critically ill non-septic patients was associated with a subsequent
      infection; therefore, BTLA may act as a biomarker to help determine nosocomial
      infection development. Additionally, BTLA expression contributed to primary and
      secondary lymphoid organ apoptotic cell loss in experimentally septic mice; thus,
      BTLA-induced apoptotic lymphocyte loss may be a mechanism for increased
      nosocomial infection risk in critically ill patients. This study had a relatively
      small human subject cohort; therefore, we feel these findings warrant future
      studies evaluating the use of BTLA as a critically ill patient nosocomial
      infection biomarker.

PMID- 24289157
TI  - Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing
      ventilator-associated pneumonia after cardiac surgery: an observational study.
AB  - BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) is a
      challenge, particularly after cardiac surgery. The use of biological markers of
      infection has been suggested to improve the accuracy of VAP diagnosis. We aimed
      to evaluate the usefulness of soluble triggering receptor expressed on myeloid
      cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. METHODS: This
      was a prospective observational cohort study of children with congenital heart
      disease admitted to the pediatric intensive care unit (PICU) after surgery and
      who remained intubated and mechanically ventilated for at least 24 hours
      postoperatively. VAP was defined by the 2007 Centers for Disease Control and
      Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and
      exhaled ventilator condensate (EVC) were collected daily, starting immediately
      after surgery until the fifth postoperative day or until extubation for
      measurement of sTREM-1. RESULTS: Thirty patients were included, 16 with VAP.
      Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment
      for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of
      cardiopulmonary bypass were not significantly diferent in patients with and
      without VAP. However, time on mechanical ventilation and length of stay in the
      PICU and in the hospital were significantly longer in the VAP group. Serum and
      mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group,
      12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all
      but two patients in the non-VAP group over the study period (p = 0.0013)
      (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative
      predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29).
      CONCLUSION: Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP
      after cardiac surgery.

PMID- 24289159
TI  - Formation of norisoprenoid flavor compounds in carrot (Daucus carota L.) roots:
      characterization of a cyclic-specific carotenoid cleavage dioxygenase 1 gene.
AB  - Carotenoids are isoprenoid pigments that upon oxidative cleavage lead to the
      production of norisoprenoids that have profound effect on flavor and aromas of
      agricultural products. The biosynthetic pathway to norisoprenoids in carrots
      (Daucus carota L.) is still largely unknown. We found the volatile norisoprenoids
      farnesylacetone, alpha-ionone, and beta-ionone accumulated in Nairobi, Rothild,
      and Purple Haze cultivars but not in Yellowstone and Creme de Lite in a pattern
      reflecting their carotenoid content. A cDNA encoding a protein with carotenoid
      cleavage dioxygenase activity, DcCCD1, was identified in carrot and was
      overexpressed in Escherichia coli strains previously engineered to produce
      different carotenoids. The recombinant DcCCD1 enzyme cleaves cyclic carotenes to
      generate alpha- and beta-ionone. No cleavage products were found when DcCCD1 was
      co-expressed in E. coli strains accumulating non-cyclic carotenoids, such as
      phytoene or lycopene. Our results suggest a role for DcCCD1 in carrot flavor
      biosynthesis.

PMID- 24289158
TI  - wKinMut: an integrated tool for the analysis and interpretation of mutations in
      human protein kinases.
AB  - BACKGROUND: Protein kinases are involved in relevant physiological functions and
      a broad number of mutations in this superfamily have been reported in the
      literature to affect protein function and stability. Unfortunately, the
      exploration of the consequences on the phenotypes of each individual mutation
      remains a considerable challenge. RESULTS: The wKinMut web-server offers direct
      prediction of the potential pathogenicity of the mutations from a number of
      methods, including our recently developed prediction method based on the
      combination of information from a range of diverse sources, including
      physicochemical properties and functional annotations from FireDB and Swissprot
      and kinase-specific characteristics such as the membership to specific kinase
      groups, the annotation with disease-associated GO terms or the occurrence of the
      mutation in PFAM domains, and the relevance of the residues in determining kinase
      subfamily specificity from S3Det. This predictor yields interesting results that
      compare favourably with other methods in the field when applied to protein
      kinases.Together with the predictions, wKinMut offers a number of integrated
      services for the analysis of mutations. These include: the classification of the
      kinase, information about associations of the kinase with other proteins
      extracted from iHop, the mapping of the mutations onto PDB structures,
      pathogenicity records from a number of databases and the classification of
      mutations in large-scale cancer studies. Importantly, wKinMut is connected with
      the SNP2L system that extracts mentions of mutations directly from the
      literature, and therefore increases the possibilities of finding interesting
      functional information associated to the studied mutations. CONCLUSIONS: wKinMut
      facilitates the exploration of the information available about individual
      mutations by integrating prediction approaches with the automatic extraction of
      information from the literature (text mining) and several state-of-the-art
      databases.wKinMut has been used during the last year for the analysis of the
      consequences of mutations in the context of a number of cancer genome projects,
      including the recent analysis of Chronic Lymphocytic Leukemia cases and is
      publicly available at http://wkinmut.bioinfo.cnio.es.

PMID- 24289160
TI  - New alkaloids from Aconitum taipaicum and their cytotoxic activities.
AB  - Three new aconitine-type C19-diterpenoid alkaloids, taipeinines A-C (1-3), were
      isolated from the roots of Aconitum taipaicum. The chemical structures of these
      three compounds were established as (1alpha,6alpha,8alpha,14alpha,16alpha)-20
      ethyl-8,14-dihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-aconitane (1),
      (1alpha,6alpha,8alpha,14alpha,16beta)-20-ethyl-8,14-dihydroxy-1,6,16-trimethoxy-4
      (methoxymethyl)-aconitane (2) and (1alpha,6alpha,8alpha,14alpha,16alpha)-20-ethyl
      1,8,14-trihydroxy-6,16-dimethoxy-4-(methoxymethyl)-aconitane (3), respectively,
      on the basis of spectroscopic analyses, mainly MS, 1D and 2D NMR. The cytotoxic
      activities of these compounds were also assayed, and the results were quite
      impressive. 

PMID- 24289161
TI  - Qualitative study of presumptive treatment of childhood malaria in third tier
      tertiary hospitals in southeast Nigeria: a focus group and in-depth study.
AB  - BACKGROUND: Presumptive treatment of childhood-malaria (PTCM) is common in
      Nigeria. Delayed laboratory result is blamed, with little attention on patients'
      and providers' roles. This study aimed to determine patient, provider and
      laboratory attributes that sustain PTCM in Nigeria. METHODS: Data collection was
      from focus-group discussions for parents/guardians, and in-depth interviews
      involving providers and laboratory scientists in two tertiary hospitals. RESULTS:
      All parents/guardians agreed to a malaria test. Majority accepted to come back
      later for full treatment, provided that some treatment was commenced. Majority
      affirmed that their interests are on their children's improvement.The providers
      practice presumptive treatment of childhood malaria, for the following reasons:
      (1) malaria is endemic and should be suspected and treated; (2) microscopy takes
      two days to be available and parents want immediate treatment for their children,
      thus delay may lead to self-medication; (3) relying on results for decision to
      treat creates an impression of incompetence; (4) rapid diagnostic test kits
      (RDTs) are not available in the consulting rooms and there is doubt about their
      reliability; (5) patients have already wasted time before being reviewed, so
      wasting more time on investigation is not advisable; (6) withhold of malaria
      treatment may be feasible in suspected uncomplicated malaria, but if severe, then
      anti-malarial treatment has to start immediately.Interviews of laboratory
      scientists showed that (1) malaria microscopy test cannot be urgent; it is done
      in batches and takes 24 hours to be ready; (2) a request of malaria test with
      other investigations on the same form, contributes to the delay; (3) RDTs are
      unavailable in the facilities. CONCLUSIONS: Provision of RDTs is the only
      feasible means to treatment of confirmed malaria at the time healthcare providers
      review a patient on day zero. In facilities that depend on microscopy; a common
      practice in resource poor countries, healthcare providers can depend on parental
      willingness to return later for full medication, to commence adjunctive care with
      antipyretics and multivitamins for uncomplicated malaria. In complicated malaria,
      supportive care - intravenous fluids, blood transfusion, oxygen therapy - can be
      commenced while awaiting the inclusion of anti-malarial drugs when the diagnosis
      of malaria is confirmed.

PMID- 24289162
TI  - Accurate identification of deamidated peptides in global proteomics using a
      quadrupole orbitrap mass spectrometer.
AB  - Deamidation of asparagine and glutamine residues is a common post-translational
      modification. Researchers often rely on mass spectrometric based proteomic
      techniques for the identification of these post-translational sites. Mass
      spectral analysis of deamidated peptides is complicated and often misassigned due
      to overlapping (13)C peak of the amidated form with the deamidated monoisotopic
      peak; these two peaks are only separated by 19.34 mDa. For proper assignment, it
      is inherently important to use a mass spectrometer with high mass measurement
      accuracy and high resolving power. Herein, mouse brain tissue lysate was prepared
      using filter-aided sample preparation (FASP) method and Stage Tip fractionation
      followed by analysis on a nanoLC coupled with a quadrupole orbitrap (Q-Exactive)
      mass spectrometer to accurately identify more than 5400 proteins. Mass spectral
      data was processed using MASCOT and ProteoIQ for accurate identification of
      peptides and proteins. MASCOT search values for precursor and MS/MS mass
      tolerances were investigated, and it was determined that data searched with
      greater than 5 ppm precursor mass tolerance resulted in the misassignment of
      deamidated peptides. Peptides that were identified with a mass measurement
      accuracy of +/-5 ppm were correctly assigned. 

PMID- 24289163
TI  - C-terminal in Sp1-like artificial zinc-finger proteins plays crucial roles in
      determining their DNA binding affinity.
AB  - BACKGROUND: It is well known that the C-terminal zinc-finger-3 in transcription
      factor Sp1 contributes more than the N-terminal zinc-finger-1 in determining
      Sp1's DNA binding capacity. Sp1-like artificial poly-zinc-finger proteins (ZFPs)
      are powerful biotechnological tools for gene-specific recognization and
      manipulation. It is important to understand whether the C-terminal fingers in the
      Sp1-like artificial ZFPs remain crucial for their DNA binding ability. Recently,
      a set of p16 promoter-specific seven-ZFPs (7ZFPs) has been constructed to
      reactivate the expression of methylation-silenced p16. These 7ZFPs contain one N
      terminal three-zinc-finger domain of Sp1 (3ZF), two Sp1-like two-zinc-finger
      domains derived from the Sp1 finger-2 and finger-3 (2ZF) in the middle and C
      terminal regions. RESULTS: In the present study, sets of variants for several
      representative 7ZFPs with the p16-binding affinity were further constructed. This
      was accomplished through finger replacements and key amino acid mutations in the
      N-terminal fingers, C-terminal fingers, and linker peptide, respectively. Their
      p16-binding activity was analysed using gel mobility shift assays. Results showed
      that the motif replacement or a key amino acid mutation (S > R) at position +2 of
      the alpha-helix in the C-terminal 2ZF domain completely abolished their p16
      binding affinity. Deletion of three amino acids in a consensus linker (TGEKP >
      TG) between finger-7 and the 6 * Histidine-tag in the C-terminal also
      dramatically abolished their binding affinity. In contrast, the replacement of
      the finger-3 in the N-terminal 3ZF domain did not affect their binding affinity,
      but decreased their binding stability. CONCLUSIONS: Altogether, the present study
      show that the C-terminal region may play crucial roles in determining the DNA
      binding affinity of Sp1-like artificial ZFPs.

PMID- 24289164
TI  - Bacterial diversity assessed by cultivation-based techniques shows predominance
      of Staphylococccus species on coins collected in Lisbon and Casablanca.
AB  - Money is usually considered a source of infections, yet survival of bacteria on
      dry metal surfaces is limited. The aim of this work was to assess the bacterial
      numbers and diversity on coins collected in Casablanca and Lisbon as these two
      cities, on different continents and only 585 km apart, have diverse cultural
      habitats, but have similar climate. A cultivation-based characterisation of the
      bacterial community showed that a relatively low number of cells per area of coin
      were found on both Moroccan Dirhams and Euros (0.014 and 0.125 colony-forming
      units (CFU) mm(-2) , respectively). Most of the bacterial isolates were located
      near the rim of the coins, and coins collected in Europe contained more CFU/area
      of coin. Coins collected in Europe and transported in pockets presented a higher
      number of bacterial isolates (maximum 0.125 CFU mm(-2) ) than coins transported
      in wallets (maximum 0.042 CFU mm(-2) ), regardless of the gender of the person
      transporting them, suggesting that temperature and moisture might be key
      parameters for bacterial survival on metallic coins. Bacterial diversity was
      higher for coins collected in Casablanca relative to coins collected in Lisbon,
      and there was no evidence that it was dependent on the gender of the person
      transporting the coins or the place of transport (pockets or wallets). Curiously,
      the percentage of Staphylococcus strains was 44% of the total isolates on both
      currencies.

PMID- 24289165
TI  - The panorama of animal leptospirosis in Rio de Janeiro, Brazil, regarding the
      seroepidemiology of the infection in tropical regions.
AB  - BACKGROUND: Leptospirosis is an important disease caused by various serovars of
      Leptospira sp. It can affect humans as well as domestic and wild animals;
      therefore, it has importance for public health, animal production, and wild
      species. The aim of this paper is to discuss the epidemiology of animal
      leptospirosis in Rio de Janeiro, Brazil, as a possible model for other tropical
      regions. In several studies conducted in the last 20 years, a total of 47 rats,
      120 dogs, 875 cows, 695 horses, 1,343 goats, 308 sheep and 351 pigs from all
      regions of the state, in addition to 107 wild mammals and 73 golden-lion tamarins
      were tested (MAT) for anti-Leptospira antibodies. RESULTS: Seroreactivity was
      frequent in all studied species, confirming that the infection is endemic in Rio
      de Janeiro. Serogroups Icterohaemorrhagiae and Sejroe were the most prevalent in
      urban and rural scenarios, respectively. This paper reviews the current knowledge
      on animal leptospirosis in Rio de Janeiro and describes important differences
      between urban versus rural cycles of the infection in various species.
      CONCLUSION: Identification of the prevailing serogroups and their reservoirs is
      essential for understanding agent-host-environment interactions under tropical
      conditions.

PMID- 24289167
TI  - Atomic structure of quantum gold nanowires: quantification of the lattice strain.
AB  - Theoretical studies exist to compute the atomic arrangement in gold nanowires and
      the influence on their electronic behavior with decreasing diameter. Experimental
      studies, e.g., by transmission electron microscopy, on chemically synthesized
      ultrafine wires are however lacking owing to the unavailability of suitable
      protocols for sample preparation and the stability of the wires under electron
      beam irradiation. In this work, we present an atomic scale structural
      investigation on quantum single crystalline gold nanowires of 2 nm diameter,
      chemically prepared on a carbon film grid. Using low dose aberration-corrected
      high resolution (S)TEM, we observe an inhomogeneous strain distribution in the
      crystal, largely concentrated at the twin boundaries and the surface along with
      the presence of facets and surface steps leading to a noncircular cross section
      of the wires. These structural aspects are critical inputs needed to determine
      their unique electronic character and their potential as a suitable catalyst
      material. Furthermore, electron-beam-induced structural changes at the atomic
      scale, having implications on their mechanical behavior and their suitability as
      interconnects, are discussed. 

PMID- 24289166
TI  - Does epilepsy in multiplex autism pedigrees define a different subgroup in terms
      of clinical characteristics and genetic risk?
AB  - BACKGROUND: Autism spectrum disorders (ASD) and epilepsy frequently occur
      together. Prevalence rates are variable, and have been attributed to age, gender,
      comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors.
      Recent studies have suggested disparate clinical and genetic settings depending
      on simplex or multiplex autism. The aim of this study was to assess: 1) the
      prevalence of epilepsy in multiplex autism and its association with genetic and
      non-genetic risk factors of major effect, intellectual disability and gender; and
      2) whether autism and epilepsy cosegregate within multiplex autism families.
      METHODS: We extracted from the Autism Genetic Resource Exchange (AGRE) database
      (n = 3,818 children from 1,264 families) all families with relevant medical data
      (n = 664 children from 290 families). The sample included 478 children with ASD
      and 186 siblings without ASD. We analyzed the following variables: seizures,
      genetic and non-genetic risk factors, gender, and cognitive functioning as
      assessed by Raven's Colored Progressive Matrices (RCPM) and Vineland Adaptive
      Behavior Scales (VABS). RESULTS: The prevalence of epilepsy was 12.8% in cases
      with ASD and 2.2% in siblings without ASD (P <10-5). With each RCPM or VABS
      measure, the risk of epilepsy in multiplex autism was significantly associated
      with intellectual disability, but not with gender. Identified risk factors
      (genetic or non-genetic) of autism tended to be significantly associated with
      epilepsy (P = 0.052). When children with prematurity, pre- or perinatal insult,
      or cerebral palsy were excluded, a genetic risk factor was reported for 6/59
      (10.2%) of children with epilepsy and 12/395 (3.0%) of children without epilepsy
      (P = 0.002). Finally, using a permutation test, there was significant evidence
      that the epilepsy phenotype co-segregated within families (P <10-4). CONCLUSIONS:
      Epilepsy in multiplex autism may define a different subgroup in terms of clinical
      characteristics and genetic risk.

PMID- 24289169
TI  - Mutations of codon 2085 in the helicase domain of ATRX are recurrent and cause
      ATRX syndrome.

PMID- 24289168
TI  - Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.
AB  - BACKGROUND: Diabetes in pregnancy carries an increased risk of adverse pregnancy
      outcomes for both the mother and foetus, but it also provides an excellent early
      opportunity for intervention in the life course for both mother and baby. In the
      context of the escalating epidemic of chronic diseases among Indigenous
      Australians, it is vital that this risk is reduced as early as possible in the
      life course of the individual. The aims of the PANDORA Study are to: (i)
      accurately assess rates of diabetes in pregnancy in the Northern Territory (NT)
      of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess
      demographic, clinical, biochemical, anthropometric, socioeconomic and early life
      development factors that may contribute to key maternal and neonatal birth
      outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post
      partum clinical outcomes for both the mothers and their babies. METHODS/DESIGN:
      Eligible participants are all NT women with diabetes in pregnancy aged 16 years
      and over. Information collected includes: standard antenatal clinical
      information, diagnosis and management of diabetes in pregnancy, socio-economic
      status, standard clinical birth information (delivery, gestational age, birth
      weight, adverse antenatal and birth outcomes). Cord blood is collected at the
      time of delivery and detailed neonatal anthropometric measurements performed
      within 72 hours of birth. Information will also be collected regarding maternal
      post-partum glucose tolerance and cardio-metabolic risk factor status,
      breastfeeding and growth of the baby up to 2 years post-partum in the first
      instance. DISCUSSION: This study will accurately document rates and outcomes of
      diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous
      Australian population. The results of this study should contribute to policy and
      clinical guidelines with the goal of reducing the future risk of obesity and
      diabetes in both mothers and their offspring.

PMID- 24289170
TI  - A benefit-risk analysis of natalizumab in the treatment of patients with multiple
      sclerosis when considering the risk of progressive multifocal
      leukoencephalopathy.
AB  - BACKGROUND: Natalizumab is a highly effective treatment for patients with
      relapsing-remitting multiple sclerosis (RRMS). Treatment with natalizumab has
      been associated with progressive multifocal leukoencephalopathy (PML), a rare yet
      serious disease of the brain. Published studies have quantified the PML risk by
      the presence of anti-JC virus antibodies, previous immunosuppressant use, and
      duration of natalizumab treatment. OBJECTIVES: The aim of this analysis was to
      evaluate the net benefits and risks for patients with RRMS receiving natalizumab
      treatment compared with fingolimod, interferon-beta, and no treatment across PML
      risk sub-groups. RESEARCH DESIGN AND METHODS: Based on previously validated MS
      model structures, a Markov cohort model was developed to assess the impact of
      treatment on quality-adjusted life years (QALYs). Natalizumab-treated patients
      were classified by PML risk sub-groups and analysed separately for short-term (2
      years) and long-term (20 years) time horizons. MAIN OUTCOME MEASURES: Main
      outcome measures included total QALYs by PML risk sub-group and the increase in
      PML risk associated with natalizumab treatment which offsets the quality of life
      benefit of comparator treatments. RESULTS: Results showed higher QALYs with
      natalizumab versus all other comparators across PML risk sub-groups over both
      time horizons. For the QALYs of natalizumab to equal the QALYs of fingolimod,
      interferon-beta, and no treatment, the risk of PML would have to increase 4.6
      84.2 times, 24.0-444.3 times, and 5.7-106.1 times, respectively (short term), and
      1.4-123.4 times, 1.5-138.3 times, and 2.2-193.7 times, respectively (long term).
      CONCLUSION: This study shows that natalizumab generates the most net health
      benefits in terms of quality-adjusted life years compared with fingolimod,
      interferon-beta, or no treatment, even when the risk of natalizumab-associated
      PML is taken into consideration. This study is limited by the availability of
      published data around natalizumab-associated PML, as well as the constraints of
      the model used to conduct the analysis.

PMID- 24289171
TI  - Single-molecule enzymology a la Michaelis-Menten.
AB  - Over the past 100 years, deterministic rate equations have been successfully used
      to infer enzyme-catalysed reaction mechanisms and to estimate rate constants from
      reaction kinetics experiments conducted in vitro. In recent years, sophisticated
      experimental techniques have been developed that begin to allow the measurement
      of enzyme-catalysed and other biopolymer-mediated reactions inside single cells
      at the single-molecule level. Time-course data obtained using these methods are
      considerably noisy because molecule numbers within cells are typically quite
      small. As a consequence, the interpretation and analysis of single-cell data
      requires stochastic methods, rather than deterministic rate equations. Here, we
      concisely review both experimental and theoretical techniques that enable single
      molecule analysis, with particular emphasis on the major developments in the
      field of theoretical stochastic enzyme kinetics, from its inception in the mid
      20th century to its modern-day status. We discuss the differences between
      stochastic and deterministic rate equation models, how these depend on enzyme
      molecule numbers and substrate inflow into the reaction compartment, and how
      estimation of rate constants from single-cell data is possible using recently
      developed stochastic approaches.

PMID- 24289172
TI  - A closer look at the FTEM framework. Response to "More of the same? Comment on
      'An integrated framework for the optimisation of sport and athlete development: a
      practitioner approach'".
AB  - The Foundations, Talent, Elite and Mastery (FTEM) framework was designed through
      the lens of a world leading high-performance sport agency to assist sporting
      stakeholders operationalise and research their whole of sport development
      pathways (Gulbin, J. P., Croser, M. J., Morley, E. J., & Weissensteiner, J. R.
      (2013). An integrated framework for the optimisation of sport and athlete
      development: A practitioner approach. Journal of Sport Sciences, 31, 1319-1331).
      In response to the commentary by MacNamara and Collins (2013) (Journal of Sports
      Sciences, doi:10.1080/02640414.2013. 855805), it was possible to document many
      inaccurate, false and misleading statements based on inattentive reading of the
      original article. We reinforce that: FTEM is a holistic framework of sport and
      athlete development and not a surrogate for a talent identification ( TID) model;
      bio-psycho-social components of development are liberally embedded throughout the
      FTEM framework; and the combined research and applied insights of development
      practitioners provide strong ecological validity for the consideration of
      stakeholders looking to explore applied approaches to athlete pathway management.

PMID- 24289173
TI  - Distractable titanium cages versus PEEK cages versus iliac crest bone grafts for
      the replacement of cervical vertebrae.
AB  - OBJECTIVE: To analyse the advantages and disadvantages of distractable titanium
      cages, polyether-etherketone cages, and iliac crest bone graft for the
      replacement of cervical vertebral bodies (VBR). METHODS: The clinical and
      radiological results of 32 patients who underwent cervical corpectomy for the
      decompression of the spinal canal were retrospectively analysed and discussed.
      RESULTS: For the vertebral body replacement the authors used distractable
      titanium cages (n = 6), PEEK cages (n = 19), and iliac crest bone graft (n = 7).
      The neurological outcomes according to postoperative JOA scores did not show
      significant differences between the three groups. PEEK cages showed a high rate
      of secondary subsidence (32%). DISCUSSION: Despite the risk of donor site
      morbidity the authors recommend iliac crest bone graft as primary choice for VBR
      because of its excellent fusion rate and its cost effectiveness. For revision
      cases we recommend titanium cages.

PMID- 24289174
TI  - Educational drama can be helpful in the management of asthmatic adolescents.

PMID- 24289175
TI  - Disulfide by Design 2.0: a web-based tool for disulfide engineering in proteins.
AB  - BACKGROUND: Disulfide engineering is an important biotechnological tool that has
      advanced a wide range of research. The introduction of novel disulfide bonds into
      proteins has been used extensively to improve protein stability, modify
      functional characteristics, and to assist in the study of protein dynamics.
      Successful use of this technology is greatly enhanced by software that can
      predict pairs of residues that will likely form a disulfide bond if mutated to
      cysteines. RESULTS: We had previously developed and distributed software for this
      purpose: Disulfide by Design (DbD). The original DbD program has been widely
      used; however, it has a number of limitations including a Windows platform
      dependency. Here, we introduce Disulfide by Design 2.0 (DbD2), a web-based,
      platform-independent application that significantly extends functionality,
      visualization, and analysis capabilities beyond the original program. Among the
      enhancements to the software is the ability to analyze the B-factor of protein
      regions involved in predicted disulfide bonds. Importantly, this feature
      facilitates the identification of potential disulfides that are not only likely
      to form but are also expected to provide improved thermal stability to the
      protein. CONCLUSIONS: DbD2 provides platform-independent access and significantly
      extends the original functionality of DbD. A web server hosting DbD2 is provided
      at http://cptweb.cpt.wayne.edu/DbD2/.

PMID- 24289176
TI  - Ultrasound-assisted extraction of stilbenoids from grape stems.
AB  - A new method for fast determination of stilbenoids from grape stems was
      developed. Ultrasound-assisted extraction was applied prior to chromatographic
      determination of stilbenoids in the extracts, and the stability of stilbenoids
      under extraction conditions was checked. A fractional experimental design was
      developed to analyze the influence on the extraction process of seven different
      extraction variables: temperature, ultrasound amplitude, ultrasonic cycle
      duration, ultrasonic probe type, time, sample-solvent ratio, and solvent
      (mixtures of ethanol and water). The most important variables for the recovery of
      major stilbenoids were studied and the final conditions optimized. With this new
      method, the main stilbenoids found in grape stems can be extracted in 15 min,
      using 75  degrees C as the extraction temperature and 80% ethanol as the
      extraction solvent, and no cleaning step with organic solvent is needed. The
      optimized method allowed for the analysis of stilbenoid content from 22 grape
      stem samples, many of them analyzed for the first time. 

PMID- 24289177
TI  - The changing burden of malaria and association with vector control interventions
      in Zambia using district-level surveillance data, 2006-2011.
AB  - BACKGROUND: Malaria control was strengthened in Zambia over the past decade. The
      two primary interventions for vector control are indoor residual spraying (IRS)
      and long-lasting insecticide-treated nets (LLINs). Using passive malaria
      surveillance data collected from 2006 to 2011 through the Zambian District Health
      Information System, the associations between increased coverage with LLINs and
      IRS and the burden of malaria in Zambia were evaluated. METHODS: National passive
      malaria surveillance data from 2006 to 2011 were analysed. A district-level,
      random-effects model with Poisson regression was used to explore the association
      between malaria cases and coverage with LLINs and IRS. Malaria cases and LLINs
      and IRS coverage were mapped to visualize spatiotemporal variation in malaria for
      each year. RESULTS: From 2006-2011, 24.6 million LLINs were distributed and 6.4
      million houses were sprayed with insecticide. Coverage with LLINs was not
      uniformly distributed over the study period and IRS was targeted to central and
      southern districts where malaria transmission was low. LLIN coverage was
      associated with a reduction in malaria cases, although an increase in the number
      of malaria cases was reported in some districts over the study period. A high
      burden of malaria persisted in north-eastern Zambia, whereas a reduction in the
      number of reported malaria cases was observed in western and southern Zambia.
      CONCLUSION: Enhanced and targeted interventions in north-eastern Zambia where the
      burden of malaria remains high, as well as efforts to sustain low malaria
      transmission in the south-west, will be necessary for Zambia to achieve the
      national goal of being malaria free by 2030.

PMID- 24289180
TI  - Body image and eating patterns among adolescents.
AB  - BACKGROUND: Data on the association between body self-perception and eating
      patterns among adolescents are scarce. This study assessed the association
      between body image and eating patterns among normal-weight, overweight and obese
      adolescents. METHODS: A cross-sectional survey (n = 1231; 12-17 years old) was
      carried out in the Balearic Islands, Spain. Anthropometry, body image, socio
      economic determinants, and food consumption were studied. RESULTS: Fifty-one
      percent of boys and sixty percent of girls that wished to be thinner had less
      than or equal to 3 eating occasions per day. Overfat girls that wish to be
      thinner skipped breakfast more frequently than normal-fat girls. Overfat boys and
      girls that wished a thinner body reported lower consumption of several food
      groups than normal-fat adolescents and overfat boys satisfied with their own body
      image (i.e. breakfast cereals, pasta and rice dishes, other oils and fats, high
      fat foods, soft drinks and chocolates in boys; and dairy products and chocolates
      in girls).A restriction of Western diet foods and energy intake was associated
      with a wish to be thinner among overfat adolescents. CONCLUSIONS: Many overfat
      boys were satisfied with their body image while practically all overfat girls
      reported wishing a thinner body. Meal patterns and food consumption were
      associated with body dissatisfaction and overfat status among adolescents.

PMID- 24289181
TI  - Patient perspective on the management of atrial fibrillation in five European
      countries.
AB  - BACKGROUND: Long-term management of chronic conditions, such as atrial
      fibrillation (AF), require frequent interactions with the healthcare systems. The
      multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was
      conducted to investigate patient satisfaction with AF management in different of
      five European healthcare systems at a time of changing treatment paradigms for
      stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS:
      Adults (>18 years) were recruited at random from the total populations of France,
      Germany, Italy, Spain and the UK using a randomized telephone dialling system. At
      least 300 respondents per country reporting to have a diagnosis of AF or
      receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm
      disturbance completed a structured telephone interview. RESULTS: Most respondents
      were satisfied with their treatment for AF over the previous 12 months, with
      85.5% (n = 1289) rating their care as good or better. Suboptimal clinical
      practices, however, were identified in several key areas. Coordination of primary
      and secondary care and a lack of patient engagement and support were particular
      issues, especially for those patients likely to have extensive contact with their
      healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for
      management of AF, most patients with AF were satisfied with their care, but for a
      greater proportion of patients, some aspects are unsatisfactory. Patient-centred
      surveys, such as the EUPS-AF, are crucial for understanding the factors that
      contribute to patient satisfaction and compliance with long-term treatment for
      chronic conditions.

PMID- 24289182
TI  - Gender-specific differences in severely injured patients between 2002 and 2011:
      data analysis with matched-pair analysis.
AB  - INTRODUCTION: Previous studies reported divergent results concerning the effect
      of gender on patient outcome after severe injury. Results suggest that women have
      better outcomes because they have lower rates of sepsis and multi-organ failure.
      The objective of this analysis was to study gender differences in a Level 1
      trauma center in Germany. METHODS: Patients who were admitted to hospital between
      2002 and 2011 with an Injury Severity Score (ISS) >=16 were included. Data were
      collected from the Trauma Registry of the German Society for Trauma Surgery and
      from hospital records. The effects of gender on a variety of parameters were
      investigated. To eliminate the influence of differences in ISS, an analysis of
      groups with similar ISS was performed. Also, a matched-pair analysis of 422
      patients was performed. RESULTS: A total of 962 patients met the inclusion
      criteria. The mortality rate was lower in male patients (25.4% versus 36.59%).
      Female patients had more severe head injuries, received less fluid volume and had
      a lower rate of sepsis. Men were more frequently involved in motorcycle accidents
      and sustained more penetrating trauma. Women were more frequently involved in
      pedestrian accidents and sustained more falls from under 3 m. The effects of
      gender were reduced when the data were analyzed by matching ISS. The mortality
      rate was significantly different in the ISS 26 to 35 group but in mostly all
      groups, the mortality rate was higher in women. In the matched-pair analysis, the
      rate of sepsis and the length of the ICU stay were significantly lower in women
      and the mortality rate showed no significant difference (28.1% for male patients
      versus 33.01% for female patients). Women died after an average of 5.22 days, and
      men died after an average of 9.02 days. CONCLUSIONS: Gender-based differences in
      patient outcome after severe trauma were observed in this study. Women are more
      likely to die in the first days after trauma. Upon extended hospital stay, women
      had a better survival rate because they had a lower rate of sepsis. No
      significant differences in mortality rate could be found, but there was a trend
      towards a higher rate in female patients.

PMID- 24289183
TI  - Management of hepatitis B in pregnant women and infants: a multicentre audit from
      four London hospitals.
AB  - BACKGROUND: Pregnant women with hepatitis B virus (HBV) infection can transmit
      the infection to their infants, screening of patients and appropriate
      interventions reduce vertical transmission. This audit was conducted to assess
      adherence to the national guidelines for management of HBV infection in
      pregnancy. METHODS: A retrospective audit was conducted on pregnant women
      diagnosed with hepatitis B on screening in antenatal clinics, across four
      hospitals in London over 2 years (2009-2010). Data was collected from antenatal
      records and discharge summaries using a standard audit form. The outcomes
      measured included HBV serological markers, HBV DNA, detection of other blood
      borne viruses and referral to hepatology services, administration of active and
      passive prophylaxis to infants at birth. Descriptive statistics are presented.
      Proportions were compared using the chi2 test and 95% confidence intervals (CI)
      were calculated for prevalence estimates. Analyses were conducted using STATA 12.
      RESULTS: HBsAg was detected in 1.05% (n = 401, 95% CI 0.95-1.16) of women
      attending an antenatal appointment, 12% (n = 48) of the women were at a high risk
      of vertical transmission (HBe Ag positive or antiHBe and HBeAg negative or HBV
      DNA >106 IU/ml). Only 62% (n = 248) women were referred to hepatology or
      specialist clinics and 29% (n = 13) of women of high infectivity were on
      antiviral agents. Testing for hepatitis C and delta virus was suboptimal. 75% (n
      = 36) of the infants at a high risk of acquisition of HBV received both active
      and passive prophylaxis. CONCLUSION: In certain sectors of London, implementation
      of the pathway for management of women with hepatitis B and their infants is
      suboptimal. National guidelines should be followed and improved intersectorial
      sharing of information is needed to reduce the risk of women of high infectivity
      being lost to follow up.

PMID- 24289184
TI  - Objective sampling design in a highly heterogeneous landscape - characterizing
      environmental determinants of malaria vector distribution in French Guiana, in
      the Amazonian region.
AB  - BACKGROUND: Sampling design is a key issue when establishing species inventories
      and characterizing habitats within highly heterogeneous landscapes. Sampling
      efforts in such environments may be constrained and many field studies only rely
      on subjective and/or qualitative approaches to design collection strategy. The
      region of Cacao, in French Guiana, provides an excellent study site to understand
      the presence and abundance of Anopheles mosquitoes, their species dynamics and
      the transmission risk of malaria across various environments. We propose an
      objective methodology to define a stratified sampling design. Following thorough
      environmental characterization, a factorial analysis of mixed groups allows the
      data to be reduced and non-collinear principal components to be identified while
      balancing the influences of the different environmental factors. Such components
      defined new variables which could then be used in a robust k-means clustering
      procedure. Then, we identified five clusters that corresponded to our sampling
      strata and selected sampling sites in each stratum. RESULTS: We validated our
      method by comparing the species overlap of entomological collections from
      selected sites and the environmental similarities of the same sites. The Morisita
      index was significantly correlated (Pearson linear correlation) with
      environmental similarity based on i) the balanced environmental variable groups
      considered jointly (p = 0.001) and ii) land cover/use (p-value << 0.001). The
      Jaccard index was significantly correlated with land cover/use-based
      environmental similarity (p-value = 0.001). CONCLUSIONS: The results validate our
      sampling approach. Land cover/use maps (based on high spatial resolution
      satellite images) were shown to be particularly useful when studying the
      presence, density and diversity of Anopheles mosquitoes at local scales and in
      very heterogeneous landscapes.

PMID- 24289185
TI  - Role of caspase-9 in the effector caspases and genome expressions, and growth of
      bovine skeletal myoblasts.
AB  - Caspase-9 has been reported as the key regulator of apoptosis, however, its role
      in skeletal myoblast development and molecular involvements during cell growth
      still remains unknown. The current study aimed to present the key role of caspase
      9 in the expressions of apoptotic caspases and genome, and cell viability during
      myoblast growth using RNA interference mediated silencing. Three small
      interference RNA sequences (siRNAs) targeting caspase-9 gene was designed and
      ligated into pSilencer plasmid vector to construct shRNA expression constructs.
      Cells were transfected with the constructs for 48 h. Results indicated that all
      three siRNAs could silence the caspase-9 mRNA expression significantly.
      Particularly, the mRNA expression level of caspase-9 in the cells transfected by
      shRNA1, shRNA2 and shRNA3 constructs were reduced by 37.85%, 68.20% and 58.14%,
      respectively. Suppression of caspase-9 led to the significant increases in the
      mRNA and protein expressions of effector caspase-3, whereas the reduction in mRNA
      and protein expressions of caspase-7. The microarray results showed that the
      suppression of caspase-9 resulted in significant upregulations of cell
      proliferation-, adhesion-, growth-, development- and division-regulating genes,
      whereas the reduction in the expressions of cell death program- and stress
      response-regulating genes. Furthermore, cell viability was significantly
      increased following the transfection. These data suggest that caspase-9 could
      play an important role in the control of cell growth, and knockdown of caspase-9
      may have genuine potential in the treatment of skeletal muscle atrophy. 

PMID- 24289186
TI  - Clusters of reaction rates and concentrations in protein networks such as the
      phosphotransferase system.
AB  - To understand the functioning of living cells, it is often helpful or even
      necessary to exploit inherent timescale disparities and focus on long-term
      dynamic behaviour. In the present study, we explore this type of behaviour for
      the biochemical network of the phosphotransferase system. We show that, during
      the slow phase that follows a fast initial transient, the network reaction rates
      are partitioned into clusters corresponding to connected parts of the reaction
      network. Rates within any of these clusters assume essentially the same value:
      differences within each cluster are vastly smaller than that from one cluster to
      another. This rate clustering induces an analogous clustering of the reactive
      compounds: only the molecular concentrations on the interface between these
      clusters are produced and consumed at substantially different rates and hence
      change considerably during the slow phase. The remaining concentrations
      essentially assume their steady-state values already by the end of the transient
      phase. Further, we find that this clustering phenomenon occurs for a large number
      of parameter values and also for models with different topologies; to each of
      these models, there corresponds a particular network partitioning. Our results
      show that, in spite of its complexity, the phosphotransferase system tends to
      behave in a rather simple (yet versatile) way. The persistence of clustering for
      the perturbed models we examined suggests that it is likely to be encountered in
      various environmental conditions, as well as in other signal transduction
      pathways with network structures similar to that of the phosphotransferase
      system. 

PMID- 24289187
TI  - Evaluation of the impact of fetal fibronectin test implementation on hospital
      admissions for preterm labour in Ontario: a multiple baseline time-series design.
AB  - OBJECTIVE: To determine the impact of a health system-wide fetal fibronectin
      (fFN) testing programme on the rates of hospital admission for preterm labour
      (PTL). DESIGN: Multiple baseline time-series design. SETTING: Canadian province
      of Ontario. POPULATION: A retrospective population-based cohort of antepartum and
      delivered obstetrical admissions in all Ontario hospitals between 1 April 2002
      and 31 March 2010. METHODS: International Classification of Diseases codes in a
      health system-wide hospital administrative database were used to identify the
      study population and define the outcome measure. An aggregate time series of
      monthly rates of hospital admissions for PTL was analysed using segmented
      regression models after aligning the fFN test implementation date for each
      institution. MAIN OUTCOME MEASURE: Rate of obstetrical hospital admission for
      PTL. RESULTS: Estimated rates of hospital admission for PTL following fFN
      implementation were lower than predicted had pre-implementation trends prevailed.
      The reduction in the rate was modest, but statistically significant, when
      estimated at 12 months following fFN implementation (-0.96 hospital admissions
      for PTL per 100 preterm births; 95% confidence interval [CI], -1.02 to -0.90, P =
      0.04). The statistically significant reduction was sustained at 24 and 36 months
      following implementation. CONCLUSIONS: Using a robust quasi-experimental study
      design to overcome confounding as a result of underlying secular trends or
      concurrent interventions, we found evidence of a small but statistically
      significant reduction in the health system-level rate of hospital admissions for
      PTL following implementation of fFN testing in a large Canadian province.

PMID- 24289188
TI  - 'Cradle cap' in puppies?

PMID- 24289190
TI  - Combined surgical and radiosurgical treatment for a symptomatic cervical
      metastasis in a case of malignant paraganglioma: a case report.
AB  - BACKGROUND: Paragangliomas of the head and neck are rare tumors. Moreover,
      malignant paragangliomas of the cervical spine are extremely rare. Currently, the
      combination of curative surgical resection and secondary adjuvant radiotherapy is
      the gold standard for treating symptomatic malignant paragangliomas. However,
      traditional treatments for malignant paraganglioma remain unsuccessful. The
      purpose of this study is to report an exceedingly rare case involving cervical
      metastasis of a malignant paraganglioma. CASE PRESENTATION: In this case report,
      we present a case involving a 72-year-old male with a history of paraganglioma of
      the neck. He had been experiencing bilateral shoulder pain, neck pain and
      weakness in the upper extremities for more than six months. Magnetic resonance
      imaging of the cervical spine revealed a metastasis at C4 with severe vertebral
      body destruction. To avoid serious complications associated with surgical
      resection, CyberKnife(r) radiosurgery (Accuray, Inc., Sunnyvale, CA, USA) was
      performed on the parapharyngeal and cervical lesions. A secondary surgery, which
      involved a posterior laminectomy at C3-6 and posterior fusion at C1-T1, was
      performed two weeks after the radiosurgery. A histological examination of the
      surgical specimen demonstrated a malignant paraganglioma. The patient regained
      strength in all extremities in the postoperative field, and his pain was
      dramatically reduced. A magnetic resonance imaging study performed three months
      after the surgery showed a reduced tumor size and spinal cord decompression.
      CONCLUSION: This case study is the first report of a patient with symptomatic
      cervical metastasis of a malignant paraganglioma treated with a combination of
      radiosurgery and posterior spinal surgery. Although the optimal treatment for
      these conditions remains unclear, concomitant treatment with radiosurgery and
      reconstructive surgery appeared to be both safe and effective in this challenging
      case.

PMID- 24289189
TI  - Guideline clinical nutrition in patients with stroke.
AB  - Stroke is regularly accompanied by dysphagia and other factors associated with
      decreased nutritional intake. Dysphagia with aspiration pneumonia and
      insufficient nutritional intake lead to worse outcome after stroke.This guideline
      is the first chapter of the guideline "Clinical Nutrition in Neurology" of the
      German Society for Clinical Nutrition (DGEM) which itself is one part of a
      comprehensive guideline about all areas of Clinical Nutrition. The thirty-one
      recommendations of the guideline are based on a systematic literature search and
      review, last updated December 31, 2011. All recommendations were discussed and
      consented at several consensus conferences with the entire DGEM guideline group.
      The recommendations underline the importance of an early screening and assessment
      of dysphagia and give advice for an evidence based and comprehensive nutritional
      management to avoid aspiration, malnutrition and dehydration. 

PMID- 24289191
TI  - More of the same? Comment on "An integrated framework for the optimisation of
      sport and athlete development: a practitioner approach".
AB  - Gulbin and colleagues (Gulbin, J. P., Croser, M. J., Morley, E. J., &
      Weissensteiner, J. R. (2013). An integrated framework for the optimisation of
      sport and athlete development: A practitioner approach. Journal of Sports
      Sciences) present a new sport and athlete development framework that evolved from
      empirical observations from working with the Australian Institute of Sport. The
      FTEM (Foundations, Talent, Elite, Mastery) framework is proposed to integrate
      general and specialised phases of development for participants within the active
      lifestyle, sport participation and sport excellence pathways. A number of issues
      concerning the FTEM framework are presented. We also propose the need to move
      beyond prescriptive models of talent identification and development towards a
      consideration of features of best practice and process markers of development
      together with robust guidelines about the implementation of these in applied
      practice.

PMID- 24289192
TI  - Acetylcholine esterase antibodies on BiOI nanoflakes/TiO2 nanoparticles
      electrode: a case of application for general photoelectrochemical enzymatic
      analysis.
AB  - To date, almost all the established photoelectrochemical (PEC) enzymatic
      biosensors require the surface-confinement procedure to immobilize enzyme as
      biorecogniton element for probing various analytes of interest. This Letter
      develops a novel example without such necessity. Specifically, we first prepared
      a BiOI nanoflakes (NFs)/TiO2 nanoparticles (NPs) p-n heterojunction as the
      photoelectrode, on the basis of which acetylcholine esterase (AChE) antibody was
      introduced via the bridging of protein A. In such a system, enzyme could keep its
      optimal state in the solution if in the absence of inhibitor; otherwise, the
      degree of enzyme inhibition would correlate closely with the concentration of
      inhibitor. After immunoreaction between AChE and its antibody, the inhibitor
      concentration could then be determined by the biocatalytic reaction-controlled
      PEC response. Integrated with other enzyme-based biosystems, this simple
      configuration could serve as a general method for assaying enzyme inhibition or
      activities. 

PMID- 24289194
TI  - Febrile and gynecological infections during pregnancy are associated with a
      greater risk of childhood eczema.
AB  - BACKGROUND: Mounting evidence suggests that fetal exposures may exert long-term
      effects on the function of the skin and of the immune system. This study aimed at
      assessing whether maternal complications during pregnancy are associated with an
      increased risk of eczema during childhood. METHODS: The associations between
      hypertension/preeclampsia, febrile infections, or gynecological infections during
      pregnancy and the occurrence of childhood eczema were studied in a population (n
      = 3907) of children, aged 3-14 yrs, living in Italy. Their parents filled in a
      standardized questionnaire about the presence of children's eczema and the events
      that occurred during pregnancy, birth, and the first year of the child's life.
      RESULTS: 7.7%, 3.8%, and 6.1% of the pregnancies were complicated by
      hypertension/preeclampsia, febrile infections, and gynecological infections,
      respectively. The prevalence of eczema was significantly higher in children born
      to mothers who had experienced febrile (35.5% vs. 22.0%; p < 0.001) or
      gynecological infections (35.3% vs. 21.6%; p < 0.001) compared with those born to
      mothers who had not suffered from that specific pregnancy complication, while
      hypertension/preeclampsia was not significantly associated with childhood eczema.
      After adjusting for potential confounders, the risk of eczema was significantly
      higher in children born to mothers who reported febrile infections during the 1st
      trimester (OR: 2.32; 95% CI: 1.11-4.82) and gynecological infections during the
      3rd trimester of pregnancy (OR: 2.73; 95% CI:1.73-4.31). CONCLUSIONS: Fetal
      exposure to febrile and gynecological infections might enhance the risk of eczema
      in the offspring, especially when occurring in specific trimesters of pregnancy.
      These findings suggest that febrile and gynecological infections might interfere
      with fetal and perinatal programming of the immune function and skin through
      different mechanisms.

PMID- 24289193
TI  - Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates
      acute respiratory distress syndrome from health.
AB  - Acute respiratory distress syndrome (ARDS) remains a significant hazard to human
      health and is clinically challenging because there are no prognostic biomarkers
      and no effective pharmacotherapy. The lung compartment metabolome may detail the
      status of the local environment that could be useful in ARDS biomarker discovery
      and the identification of drug target opportunities. However, neither the utility
      of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the
      optimal analytical platform for metabolite identification is established. To
      address this, we undertook a study to compare metabolites in BALF samples from
      patients with ARDS and healthy controls using a newly developed liquid
      chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics.
      Following initial testing of three different high-performance liquid
      chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and
      hydrophilic interaction chromatography (HILIC) were the most informative
      chromatographic methods because they yielded the most and highest quality data.
      Following confirmation of metabolite identification, statistical analysis
      resulted in 37 differentiating metabolites in the BALF of ARDS compared with
      health across both analytical platforms. Pathway analysis revealed networks
      associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid
      biosynthesis, phospholipids, and purine metabolism in the ARDS BALF. The
      complementary analytical platforms of RPLC and HILIC-LC generated informative,
      insightful metabolomics data of the ARDS lung environment. 

PMID- 24289195
TI  - Extremely rare coincidence of non-radiographic axial spondyloarthropathy HLA-B27
      positive and Stiff Person Syndrome--rheumatologist point of view.
AB  - Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder
      characterized by progressive stiffness and rigidity of truncal muscles
      accompanied with co-contraction of agonist-antagonist muscles. Our 51-year-old
      female patient was presented for the first time to physiatrists in 2006 and
      diagnosed with axial-spondyloarthropathy (SpA) HLA-B27 positive. SPS was
      diagnosed 7 years after initial symptoms. SPS should be taken into consideration
      in HLA-B27 positive patients if stiffness of paravertebral and abdominal muscles
      progresses during SpA therapy. 

PMID- 24289196
TI  - Incidence of full-thickness rotator cuff tear after subacromial corticosteroid
      injection: a 12-week prospective study.
AB  - INTRODUCTION: Rotator cuff tears (RCT) are a common source of shoulder pain, with
      an incidence ranging between 5% and 40%. The influence of corticosteroid
      injections on the incidence of RCT remains unknown. The aim of this study was to
      estimate the incidence of full-thickness RCT 12 weeks after a subacromial
      corticosteroid injection in patients with shoulder pain. PATIENTS AND METHOD: We
      made a prospective, open-label study in patients with unilateral painful shoulder
      without previous local corticosteroid injection. Ultrasound assessments were made
      at the first (baseline) and last (Week 12) visits by an experienced radiologist.
      A rheumatologist did the clinical examination. Patients with full-thickness RCT
      at the first visit were excluded. All patients received a subacromial injection
      of triamcinolone acetate 40 mg. RESULTS: One hundred and two patients with
      shoulder pain were initially evaluated: 49 (48%) were excluded due to full
      thickness RCT on ultrasound assessment. Therefore, 53 patients completed the
      study (34 female, mean age 60.8 years, mean time of evolution 9.6 months). In the
      first ultrasound evaluation, 24 patients (45.3%) had a partial-thickness tear. At
      12 weeks after the corticosteroid injection, 9 (17%) patients developed full
      thickness RCT, 66.6% of which occurred in patients with previous partial
      thickness RCT. Corticosteroid injection significantly improved symptoms (p =
      0.0001 for pain VAS score) and range of motion (p = 0.002 for forward elevation
      and external rotation). CONCLUSIONS: Seventeen percent of patients with shoulder
      pain suffered a full-thickness RCT 12 weeks after subacromial corticosteroid
      injection. Corticosteroid injection is highly effective in improving clinical
      symptoms of rotator cuff tendinopathy at 12 weeks.

PMID- 24289197
TI  - A nationwide survey on the epidemiology and clinical features of eosinophilic
      granulomatosis with polyangiitis (Churg-Strauss) in Japan.
AB  - OBJECTIVE: We conducted a cross-sectional nationwide survey to determine
      eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) prevalence
      and clinical features in Japan. METHODS: Data for EGPA patients in 2008 were
      collected from 1,564 hospitals. In total, 965 patients were reported from 365
      departments. In a second survey, clinical data for 473 patients were obtained.
      RESULTS: We estimated that 1,866 (95% CI: 1,640-2,092) patients have EGPA in
      Japan (prevalence, 17.8/1,000,000). Of the 473 patients in the second survey, 315
      fulfilled American College of Rheumatology (ACR) criteria or Lanham's criteria
      for EGPA. The mean age (+/- SD) of the 315 at onset was 55 +/- 14 years, male to
      female ratio 1:2. 93% of patients had neurological manifestations, which were the
      organ system most frequently involved. Among 277 patients tested for
      myeloperoxidase (MPO)-/p anti-neutrophil cytoplasmic antibody (ANCA), 139 (50%)
      were positive, while only 6 of 238 were positive for proteinase3 (PR3)-/cANCA.
      MPO-ANCA-positive patients had renal involvement, mucous membrane or
      ophthalmological symptoms, and ENT symptoms more frequently, whereas cutaneous
      lesions and cardiovascular involvement were less common. CONCLUSION: The
      prevalence of EGPA and the frequency of MPO-/p-ANCA-positivity in Japanese EGPA
      patients were mostly similar to those of Western countries. However, female
      predominance and a high frequency of neurological manifestations characterized
      Japanese patients.

PMID- 24289198
TI  - A case of angioimmunoblastic T-cell lymphoma with high serum VEGF preceded by
      RS3PE syndrome.
AB  - We report the case of a 76-year-old man diagnosed with angioimmunoblastic T-cell
      lymphoma (AITL) with high serum vascular endothelial growth factor (VEGF)
      preceded by Remitting seronegative symmetrical synovitis with pitting edema
      syndrome. He suffered respiratory discomfort caused by large amounts of pleural
      effusion. Interestingly, changes in serum VEGF measured over time were similar to
      changes in pleural effusion. Whether VEGF is related to the pathological
      condition of AITL is a very important question. 

PMID- 24289199
TI  - The first case of adult-onset PFAPA syndrome in Japan.
AB  - A 26-year-old woman presented with fever and pharyngitis. She previously
      experienced four periodic febrile episodes at 30- to 40-day intervals. We
      suspected periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)
      syndrome, and prescribed predisolone, thereby her fever rapidly subsided. Her
      febrile episodes improved after daily cimetidine treatment. Genetic testing
      results of genomic DNA for periodic fever syndromes were negative, although she
      was heterozygous for p.Glu148Gln variation in MEFV, supporting the diagnosis of
      PFAPA syndrome. 

PMID- 24289200
TI  - Ultrasonography predicts achievement of Boolean remission after DAS28-based
      clinical remission of rheumatoid arthritis.
AB  - OBJECTIVES: To determine whether ultrasonography (US) predicts Boolean remission
      in rheumatoid arthritis (RA) patients who had achieved disease activity score in
      28 joints (DAS28)-based remission criteria. METHODS: Thirty-one RA patients in
      DAS28-based clinical remission were recruited. US semiquantitatively determined
      Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and
      all metacarpophalangeals and proximal interphalangeals. Total GS score and total
      PD score were calculated as the sum of individual scores for each joint. RESULTS:
      Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean
      remission criteria at the end of study. Both total GS and total PD scores at
      baseline were significantly lower in Boolean remission group than non-remission
      group. There was no significant difference in other baseline parameters,
      including duration of disease, duration of remission, mTSS, and disease activity
      composite parameters between the two groups. Among the factors for Boolean
      remission criteria at 2 years, patient global assessment score was associated
      with total GS score at the entry, while swollen joint count was related to total
      PD score. CONCLUSIONS: Null or low grade of GS and PD findings in US are
      associated with achieving Boolean remission. Thus, US is essential for assessment
      and prediction of "deeper remission" of RA.

PMID- 24289201
TI  - Therapeutic effects of sunitinib, one of the anti-angiogenetic drugs, in a murine
      arthritis.
AB  - OBJECTIVES: The purpose of this study was to confirm the inhibitory effects of
      sunitinib, an angiogenesis inhibitor that targets tyrosine kinases of vascular
      endothelial growth factor receptor (VEGFR) family and platelet-derived growth
      factor receptor (PDGFR) family, on arthritis in mice with type II collagen
      induced arthritis (CIA). METHODS: Sunitinib at a concentration of 30 or 60
      mg/kg/day was intraperitoneally administered to mice with CIA. We compared the
      changes in arthritis score over time, pathological score, bone density, and
      microvascular density in synovial membrane between the vehicle and treatment
      groups. RESULTS: In the sunitinib-treated groups, the arthritis score decreased
      in a dose-dependent manner in comparison with that in the vehicle group.
      Furthermore, improvement in the pathological score, inhibitory tendency of loss
      in the bone density, and a decrease in the synovial microvascular density were
      also observed in the sunitinib-treated groups. CONCLUSIONS: Sunitinib remarkably
      inhibited arthritis, particularly synovial angiogenesis in a murine CIA model.
      This compound may be useful for treating arthritis.

PMID- 24289202
TI  - A new flavonol glycoside and biological activities of Adenanthera pavonina L.
      leaves.
AB  - Adenanthera pavonina is a plant belonging to family Fabaceae. The 95% ethanol
      extract (EtOH) of the dried powdered leaves of the plant and successive extracts
      with solvents of increasing polarities were prepared. Fractionation of the
      successive aqueous EtOH extract on polyamide column and purification of the
      isolated compounds on Sephadex LH20 led to the isolation of a new methoxy
      flavonol glycoside named as quercetin 3-O-alpha-dirhamnopyranosyl-(1''' -> 2",1""
      -> 6")-beta-glucopyranoside-4'-methoxy (1), as well as kaempferol-3-O-alpha
      dirhamnopyranosyl-(1''' -> 2",1"" -> 6")-beta-glucopyranoside (2), isovitexin
      (3), quercetin-3-O-rhamnopyranosyl(1''' -> 4")-beta-glucopyranoside (4),
      quercetin-3-O-beta-glucopranoside-4'-O-rhamnopyranoside (5), kaempferol-3-O-alpha
      rhamnopyranosyl(1''' -> 2")-beta-glucopyranoside (6), quercetin-3-O
      rhamnopyranosyl(1''' -> 2")-beta-glucopyranoside (7), quercetin-3-O-beta
      glucopyranoside (8), kaempferol (9) and quercetin (10). Structures of the
      isolated compounds were established by spectroscopic analysis. Antioxidant
      activities of EtOH extract, successive extracts and compounds 1 and 2 were
      evaluated. The ethyl acetate (EtOAc) extract and EtOH extract showed 62.67% and
      49.30% free radical scavenging activity, respectively. Cytotoxic activities of
      the EtOH extract and compounds (1) and (2) were evaluated. The EtOH extract
      showed a significant cytotoxic activity against Hep G-2 (IC50 = 2.50 MUg) as
      compared with cisplatin (IC50>10 MUg).

PMID- 24289203
TI  - Nutritional knowledge as a determinant of vitamin and mineral supplementation
      during pregnancy.
AB  - BACKGROUND: Pregnancy is a critical period for both woman and baby from a
      nutritional perspective. Nutritional education is considered an important tool
      for promoting a healthy lifestyle, but has not been studied as a determinant for
      maternal use of supplements during pregnancy, especially in Romania, where
      evidence about pregnancy and nutrition is scarce. This study aimed to evaluate
      the relationship between nutritional knowledge and the use of folic acid, iron
      and multivitamin supplements during pregnancy and to assess the influence of
      socio-demographic factors and prenatal care. METHODS: We conducted a cross
      sectional study on a sample of 400 pregnant women admitted to the Cuza-Voda
      Obstetrics and Gynaecology Clinical Hospital in Iasi, Romania, during August
      September 2010. We collected self-reported data regarding socio-demographic
      characteristics, number of prenatal check-ups and the use of folic acid, iron and
      multivitamin supplements during pregnancy. We assessed nutritional knowledge
      using a standardized questionnaire divided into three sections: general
      nutritional recommendations for pregnant women; the roles of nutrients; and
      sources of nutrients. We used logistic regression to analyse the associations
      between these factors. RESULTS: The prevalence of the use of supplements during
      pregnancy was 48% for folic acid, 45.3% for iron and 68% for multivitamins. Above
      average nutritional knowledge was independently associated with the use of folic
      acid (aOR, 4.7; 95% CI, 1.6-13.8), iron (aOR, 2.6; 95% CI, 1.2-5.7) and
      multivitamins (aOR, 2.8; 95% CI, 1.2-6.8). The use of folic acid was
      independently associated with a higher level of formal education (aOR, 5.2; 95%
      CI, 2.1-12.8) and an early start in prenatal care (aOR, 3.4; 95% CI, 1.0-11.1).
      Women with a higher education (aOR, 2.3; 95% CI, 1.1-4.9), more than 10 prenatal
      visits (aOR, 7.2; 95% CI, 3.4-15.0) and those who received advice on
      breastfeeding (aOR, 2.0; 95% CI, 1.1-3.5) were more likely to use iron during
      pregnancy. Similar results were found when analysing the contributing factors for
      the use of multivitamins: more than 12 years of schooling (aOR, 3.4; 95% CI, 1.4
      7.9) and appropriate prenatal care (aOR, 9.4; 95% CI, 4.5-19.5). CONCLUSIONS:
      Level of nutritional knowledge has a strong independent association with the use
      of supplements during pregnancy.

PMID- 24289204
TI  - Modules identification in protein structures: the topological and geometrical
      solutions.
AB  - The identification of modules in protein structures has major relevance in
      structural biology, with consequences in protein stability and functional
      classification, adding new perspectives in drug design. In this work, we present
      the comparison between a topological (spectral clustering) and a geometrical (k
      means) approach to module identification, in the frame of a multiscale analysis
      of the protein architecture principles. The global consistency of an adjacency
      matrix based technique (spectral clustering) and a method based on full rank
      geometrical information (k-means) give a proof-of-concept of the relevance of
      protein contact networks in structure determination. The peculiar "small-world"
      character of protein contact graphs is established as well, pointing to average
      shortest path as a mesoscopic crucial variable to maximize the efficiency of
      within-molecule signal transmission. The specific nature of protein architecture
      indicates topological approach as the most proper one to highlight protein
      functional domains, and two new representations linking sequence and topological
      role of aminoacids are demonstrated to be of use for protein structural analysis.
      Here we present a case study regarding azurin, a small copper protein implied in
      the Pseudomonas aeruginosa respiratory chain. Its pocket molecular shape and its
      electron transfer function have challenged the method, highlighting its
      potentiality to catch jointly the structure and function features of protein
      structures through their decomposition into modules. 

PMID- 24289205
TI  - Severe pan-uveitis in a patient treated with vemurafenib for metastatic melanoma.
AB  - BACKGROUND: Vemurafenib, an inhibitor of genetically activated BRAF, is now
      commonly prescribed for metastatic melanoma harboring a BRAF mutation. Reports on
      side effects have focused on cutaneous complications. We here present a case of a
      severe pan-uveitis associated with vemurafenib use. CASE PRESENTATION: A 63-year
      old female was treated with the BRAF inhibitor vemurafenib for metastatic
      melanoma. After seven weeks of treatment, she developed near-complete visual loss
      in the course of a few days, as a result of severe uveitis. Vemurafenib had to be
      discontinued and systemic and topical corticosteroids were initiated. The visual
      symptoms improved slowly, however the cerebral metastases progressed and the
      patient died from her disease. CONCLUSION: Treatment with vemurafenib has become
      an important component of standard clinical care for patients with metastatic
      melanoma. In addition, it is one of the best examples of genotype-directed
      therapy. This case illustrates that vemurafenib-induced uveitis can develop fast
      and be slow to resolve. Awareness of this potentially severe side effect is of
      major importance to oncologists and aggressive treatment should be considered.

PMID- 24289206
TI  - Association between systemic hemodynamics and septic acute kidney injury in
      critically ill patients: a retrospective observational study.
AB  - INTRODUCTION: The role of systemic hemodynamics in the pathogenesis of septic
      acute kidney injury (AKI) has received little attention. The purpose of this
      study was to investigate the association between systemic hemodynamics and new or
      persistent of AKI in severe sepsis. METHODS: A retrospective study between 2006
      and 2010 was performed in a surgical ICU in a teaching hospital. AKI was defined
      as development (new AKI) or persistent AKI during the five days following
      admission based on the Acute Kidney Injury Network (AKIN) criteria. We studied
      the association between the following hemodynamic targets within 24 hours of
      admission and AKI: central venous pressure (CVP), cardiac output (CO), mean
      arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen
      saturation (ScvO2) or mixed venous oxygen saturation (SvO2). RESULTS: This study
      included 137 ICU septic patients. Of these, 69 had new or persistent AKI. AKI
      patients had a higher Simplified Acute Physiology Score (SAPS II) (57 (46 to 67)
      vs. 45 (33 to 52), P < 0.001) and higher mortality (38% vs. 15%, P = 0.003) than
      those with no AKI or improving AKI. MAP, ScvO2 and CO were not significantly
      different between groups. Patients with AKI had lower DAP and higher CVP (P =
      0.0003). The CVP value was associated with the risk of developing new or
      persistent AKI even after adjustment for fluid balance and positive end
      expiratory pressure (PEEP) level (OR = 1.22 (1.08 to 1.39), P = 0.002). A linear
      relationship between CVP and the risk of new or persistent AKI was observed.
      CONCLUSIONS: We observed no association between most systemic hemodynamic
      parameters and AKI in septic patients. Association between elevated CVP and AKI
      suggests a role of venous congestion in the development of AKI. The paradigm that
      targeting high CVP may reduce occurrence of AKI should probably be revised.
      Furthermore, DAP should be considered as a potential important hemodynamic target
      for the kidney.

PMID- 24289207
TI  - The Netherlands Cohort Study-Meat Investigation Cohort; a population-based cohort
      over-represented with vegetarians, pescetarians and low meat consumers.
AB  - BACKGROUND: Vegetarian diets have been associated with lower risk of chronic
      disease, but little is known about the health effects of low meat diets and the
      reliability of self-reported vegetarian status. We aimed to establish an
      analytical cohort over-represented with vegetarians, pescetarians and 1 day/week
      meat consumers, and to describe their lifestyle and dietary characteristics. In
      addition, we were able to compare self-reported vegetarians with vegetarians
      whose status has been confirmed by their response on the extensive food frequency
      questionnaire (FFQ). STUDY METHODS: Embedded within the Netherlands Cohort Study
      (n = 120,852; including 1150 self-reported vegetarians), the NLCS-Meat
      Investigation Cohort (NLCS-MIC) was defined by combining all FFQ-confirmed
      vegetarians (n = 702), pescetarians (n = 394), and 1 day/week meat consumers (n =
      1,396) from the total cohort with a random sample of 2-5 days/week- and 6-7
      days/week meat consumers (n = 2,965 and 5,648, respectively). RESULTS:
      Vegetarians, pescetarians, and 1 day/week meat consumers had more favorable
      dietary intakes (e.g., higher fiber/vegetables) and lifestyle characteristics
      (e.g. lower smoking rates) compared to regular meat consumers in both sexes.
      Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat
      consumers. 75% of vegetarians with a prevalent cancer at baseline had changed to
      this diet after diagnosis. 50% of self-reported vegetarians reported meat or fish
      consumption on the FFQ. Although the misclassification that occurred in terms of
      diet and lifestyle when merely relying on self-reporting was relatively small,
      the impact on associations with disease risk remains to be studied. CONCLUSION:
      We established an analytical cohort over-represented with persons at the lower
      end of the meat consumption spectrum which should facilitate prospective studies
      of major cancers and causes of death using >=20.3 years of follow-up.

PMID- 24289210
TI  - Chewing ability, nutritional status and quality of life.
AB  - In the literature, most researchers evaluate individuals' nutritional status and
      chewing ability by types of foods chosen or blood test. However, most of previous
      researches enrolled small sample size and the results might be influenced by
      personal preference of foods as well as the individuals' response to invasive
      examination. In this study, researchers assessed individuals' nutritional status
      and chewing ability with non-invasive test and excluded the personal preference
      of foods. This study had two aims: first, to explore associations between chewing
      ability, edentulous or dentulous, self-perceived oral health and individuals'
      nutritional status and quality of life; second, to assess whether the association
      proposed by Locker's model is valid. This study used the database of Phase I
      'Publicly-funded Denture Installation Plan for the Elderly' of Kaohsiung City
      Government. Nine hundred and fifty-four subjects aged 65 years and older
      completed the questionnaires for data analysis. The research results supported
      and verified the theoretical model proposed by Locker. Individual's chewing
      ability associated significantly with his/her nutritional status and quality of
      life. The results demonstrated that better chewing ability of the elderly leads
      to better nutritional status and quality of life. The appropriateness of the
      indicators and measurements of individual's chewing ability and nutritional
      status used in this study has been evaluated and presented. These indicators and
      measurements are suggested to be generally used for clinical or research
      application on future-related issues. Consequently, the maintenance or
      improvement in the chewing ability of the elderly is extremely beneficial to
      healthy ageing.

PMID- 24289208
TI  - Association between smoking status and the parameters of vascular structure and
      function in adults: results from the EVIDENT study.
AB  - BACKGROUND: The present study analyses the relation between smoking status and
      the parameters used to assess vascular structure and function. METHODS: This
      cross-sectional, multi-centre study involved a random sample of 1553 participants
      from the EVIDENT study. MEASUREMENTS: The smoking status, peripheral augmentation
      index and ankle-brachial index were measured in all participants. In a small
      subset of the main population (265 participants), the carotid intima-media
      thickness and pulse wave velocity were also measured. RESULTS: After controlling
      for the effect of age, sex and other risk factors, present smokers have higher
      values of carotid intima-media thickness (p = 0.011). Along the same lines,
      current smokers have higher values of pulse wave velocity and lower mean values
      of ankle-brachial index but without statistical significance in both cases.
      CONCLUSIONS: Among the parameters of vascular structure and function analysed,
      only the IMT shows association with the smoking status, after adjusting for
      confounders.

PMID- 24289211
TI  - Low cost labeling with highlighter ink efficiently visualizes developing blood
      vessels in avian and mouse embryos.
AB  - To understand how blood vessels form to establish the intricate network during
      vertebrate development, it is helpful if one can visualize the vasculature in
      embryos. We here describe a novel labeling method using highlighter ink, easily
      obtained in stationery stores with a low cost, to visualize embryo-wide
      vasculatures in avian and mice. We tested 50 different highlighters for
      fluorescent microscopy with filter sets equipped in a standard fluorescent
      microscope. The yellow and violet inks yielded fluorescent signals specifically
      detected by the filters used for green fluorescent protein (GFP) and red
      fluorescent protein (RFP) detections, respectively. When the ink solution was
      infused into chicken/quail and mouse embryos, vasculatures including large
      vessels and capillaries were labeled both in living and fixed embryos. Ink
      infused embryos were further subjected to histological sections, and double
      stained with antibodies including QH-1 (quail), alpha smooth muscle actin
      (alphaSMA), and PECAM-1 (mouse), revealing that the endothelial cells were
      specifically labeled by the infused highlighter ink. Highlighter-labeled signals
      were detected with a resolution comparable to or higher than signals of
      fluorescein isothiocyanate (FITC)-lectin and Rhodamine-dextran, conventionally
      used for angiography. Furthermore, macroconfocal microscopic analyses with ink
      infused embryos visualized fine vascular structures of both embryo proper and
      extra-embryonic plexus in a Z-stack image of 2400 MUm thick with a markedly high
      resolution. Together, the low cost highlighter ink serves as an alternative
      reagent useful for visualization of blood vessels in developing avian and mouse
      embryos and possibly in other animals. 

PMID- 24289209
TI  - Suppression of anoikis in human intestinal epithelial cells: differentiation
      state-selective roles of alpha2beta1, alpha3beta1, alpha5beta1, and alpha6beta4
      integrins.
AB  - BACKGROUND: Regulation of anoikis in human intestinal epithelial cells (IECs)
      implicates differentiation state-specific mechanisms. Human IECs express distinct
      repertoires of integrins according to their state of differentiation. Therefore,
      we investigated whether alpha2beta1, alpha3beta1, alpha5beta1, and alpha6beta4
      integrins perform differentiation state-specific roles in the suppression of IEC
      anoikis. RESULTS: Human (HIEC, Caco-2/15) IECs were exposed to specific
      antibodies that block the binding activity of integrin subunits (alpha2, alpha3,
      alpha5, alpha6, beta1 or beta4) to verify whether or not their inhibition induced
      anoikis. The knockdown of alpha6 was also performed by shRNA. Additionally,
      apoptosis/anoikis was induced by pharmacological inhibition of Fak (PF573228) or
      Src (PP2). Anoikis/apoptosis was assayed by DNA laddering, ISEL, and/or caspase
      activity (CASP-8, -9, or -3). Activation levels of Fak and Src, as well as
      functional Fak-Src interactions, were also assessed. We report herein that
      differentiated IECs exhibit a greater sensitivity to anoikis than
      undifferentiated ones. This involves an earlier onset of anoikis when kept in
      suspension, as well as significantly greater contributions from beta1 and beta4
      integrins in the suppression of anoikis in differentiated cells, and functional
      distinctions between beta1 and beta4 integrins in engaging both Fak and Src, or
      Src only, respectively. Likewise, Fak performs significantly greater
      contributions in the suppression of anoikis in differentiated cells.
      Additionally, we show that alpha2beta1 and alpha5beta1 suppress anoikis in
      undifferentiated cells, whereas alpha3beta1 does so in differentiated ones.
      Furthermore, we provide evidence that alpha6beta4 contributes to the suppression
      of anoikis in a primarily alpha6 subunit-dependent manner in undifferentiated
      cells, whereas this same integrin in differentiated cells performs significantly
      greater contributions in anoikis suppression than its undifferentiated state
      counterpart, in addition to doing so through a dependence on both of its
      subunits. CONCLUSIONS: Our findings indicate that the suppression of human IEC
      anoikis implicates differentiation state-selective repertoires of integrins,
      which in turn results into distinctions in anoikis regulation, and sensitivity,
      between undifferentiated and differentiated IECs. These data further the
      functional understanding of the concept that the suppression of anoikis is
      subjected to cell differentiation state-selective mechanisms.

PMID- 24289212
TI  - Describing antimicrobial use and reported treatment efficacy in Ontario swine
      using the Ontario Swine Veterinary-based Surveillance program.
AB  - BACKGROUND: The objective of this work was to retrospectively assess records
      received through the Ontario Swine Veterinary-based Surveillance program July
      2007 - July 2009 to describe and assess relationships between reported treatment
      failure, antimicrobial use, diagnosis and body system affected. RESULTS:
      Antimicrobial use occurred in 676 records, 80.4% of all records recording
      treatment (840). The most commonly used antimicrobials were penicillin (34.9%),
      tetracyclines (10.7%) and ceftiofur (7.8%), and the use of multiple
      antimicrobials occurred in 141/676 records (20.9%). A multi-level logistic
      regression model was built to describe the probability of reported treatment
      failure. The odds of reported treatment failure were significantly reduced if the
      record indicated that the gastro-intestinal (GI) system was affected, as compared
      to all other body systems (p < 0.05). In contrast, the odds of reported treatment
      failure increased by 1.98 times if two antimicrobials were used as compared to
      one antimicrobial (p = 0.009) and by 6.52 times if three or more antimicrobials
      were used as compared to one antimicrobial (p = 0.005). No significant increase
      in reported treatment failure was seen between the use of two antimicrobials and
      three or more antimicrobials. No other antimicrobials were significantly
      associated with reported treatment failure after controlling for body system and
      the number of antimicrobials used. CONCLUSIONS: Failure of antimicrobial
      treatment is more likely to occur in non-GI conditions, as compared to GI
      conditions and the use of multiple antimicrobial products is also associated with
      an increased probability of antimicrobial treatment failure. The authors suggest
      that a more preventative approach to herd health should be taken in order to
      reduce antimicrobial inputs on-farm, including improved immunity via vaccination,
      management and biosecurity strategies. Furthermore, improved immunity may be
      viewed as a form of antimicrobial stewardship to the industry by reducing
      required antimicrobial inputs and consequently, reduced selection pressure for
      AMR.

PMID- 24289213
TI  - Pathological risk factors in upper urinary tract cancer.
AB  - AIMS: To evaluate pathological factors for prognosis, intravesical recurrence and
      distant metastasis of upper urinary tract cancer. METHODS: This clinical study
      included 105 patients with renal pelvic and ureteral cancer who were treated at
      the Kochi Medical School Hospital between 1982 and 2008. Of these patients, 90
      who underwent nephroureterectomy were analyzed for pathological risk factors
      using uni- and multivariate analysis. RESULTS: The mean follow-up period of the
      105 patients was 53 months. The disease-specific survival rates were 70% and 62%
      at 3 and 5 years. Twenty-three patients (23%) developed intravesical recurrence,
      and the mean and median times to recurrence were 18.8 and 9.2 months,
      respectively. Seventeen patients (19%) had distant metastasis, and the mean and
      median times to distant metastasis were 25.2 and 25.3 months, respectively.
      Multivariate analysis identified the pathological grade as an independent risk
      factor for prognosis (P = 0.031), age (>=67 years) and tumor diameter (>=3 cm) as
      independent risk factors for intravesical recurrence (P = 0.007 and 0.003,
      respectively), and the pathological grade (G1,2 vs G3) and lymphatic invasion as
      independent risk factors for distant metastasis (P = 0.006 and 0.003,
      respectively). CONCLUSION: Patients with higher-grade upper urinary tract cancer
      show a poor prognosis, and often develop distant metastasis, suggesting the need
      for careful postoperative follow-up. Those with lymphatic invasion or tumors of 3
      cm or more in diameter frequently develop intravesical recurrence and distant
      metastasis, respectively, indicating the need for strict follow-up.

PMID- 24289214
TI  - Water-dispersible TiO2 nanoparticles via a biphasic solvothermal reaction method.
AB  - A biphasic solvothermal reaction method has been used for the synthesis of TiO2
      nanoparticles (NPs). In this method, hydrolysis and nucleation occur at the
      interface of organic phase (titanium (IV) n-propoxide and stearic acid dissolved
      in toluene) and water phase (tert-butylamine dissolved in water) resulting in the
      nucleation of the stearic acid-capped TiO2 NPs. These NPs are hydrophilic due to
      hydrophobic stearic acid ligands and could be dispersed in toluene, but not in
      water. These stearic acid-capped TiO2 NPs were surface-modified with 2,3
      dimercaptosuccinic acid (DMSA) in order to make them water soluble. The resultant
      TiO2 NPs were easily redispersed in water without any noticeable aggregation. The
      Rietveld profile fitting of X-ray diffraction (XRD) pattern of the TiO2 NPs
      revealed highly crystalline anatase structure. The average crystallite size of
      TiO2 NPs was calculated to be 6.89 nm, which agrees with TEM results. These
      results have important implications for the use of TiO2 in biomedical,
      environmental, and industrial applications. 

PMID- 24289215
TI  - Exercise intervention in breast cancer patients with aromatase inhibitor
      associated arthralgia: a pilot study.
AB  - Aromatase inhibitors (AIs) block estrogen synthesis and are commonly used as
      adjuvant treatments for breast cancer patients. A common side effect is joint
      pain. This was a pilot study to examine implementation of an exercise program in
      reducing joint pain and improving quality of life (QoL) and functional
      performance in breast cancer patients treated with AIs. Twenty-six participants
      completed an 8-week, home-based program that combined upper and lower body
      resistance exercises with self-selected aerobic exercises. We measured: (1)
      anthropometry (2) functional performance (grip strength, biceps curl to
      exhaustion, and sit-to-stand and cardiovascular endurance (3-min step test).
      Joint pain and QoL were assessed using self-administered surveys. Participants
      reported a significantly lower number of painful joints, an improvement in QoL
      and a reduction in depressive symptoms. Significant improvements in grip
      strength, biceps curl, and sit-to-stand (by 14%, 51% and 15% respectively) were
      also observed. However, we found no significant changes in cardiovascular
      endurance or in anthropometric measures. An 8-week, home-based exercise program
      may provide potential benefit to the breast cancer patients undergoing AI
      treatment by reducing joint pain, improving functional performance and QoL, and
      reducing depressive symptoms. Further studies are needed to confirm these
      results. 

PMID- 24289216
TI  - A comparison of intramuscular diamorphine and intramuscular pethidine for labour
      analgesia: a two-centre randomised blinded controlled trial.
AB  - OBJECTIVE: Intramuscular (i.m.) pethidine is used worldwide for labour analgesia
      and i.m. diamorphine usage has increased in the UK in the last 15 years. This
      trial aims to ascertain the relative efficacy and adverse effects of diamorphine
      and pethidine for labour pain. DESIGN: Prospective, parallel-arm randomised
      controlled trial with blinding of participants, care-givers and outcome
      assessors. SETTING: Maternity units in two District General Hospitals in the UK.
      POPULATION: After written informed consent, 484 women were randomised and
      recruited (244 diamorphine, 240 pethidine). Inclusion criteria included women 16
      years or older, established labour, singleton pregnancy, 37-42 weeks of gestation
      and weight 60-120 kg. METHODS: On request of i.m. analgesia, participants
      received either 150 mg pethidine or 7.5 mg diamorphine based on computer
      generated block randomisation. MAIN OUTCOME MEASURES: Maternal-reduction in pain
      intensity from baseline (10-cm visual analogue scale) at 60 minutes and over the
      3-hour period after drug administration. Neonatal-requirement for resuscitation
      and Apgar score at 1 minute. RESULTS: Diamorphine provided modestly improved pain
      relief at 60 minutes, mean difference 1 cm (95% confidence interval [CI] 0.5
      1.5), and over the 3 hours, mean difference 0.7 cm (95% CI 0.3-1.1). However,
      average length of labour in women receiving diamorphine was 82 minutes longer
      (95% CI 39-124) and therefore they experienced more pain overall. There were no
      statistically significant differences in primary neonatal outcomes. CONCLUSIONS:
      There is a modest difference between the analgesia provided by diamorphine or
      pethidine for labour analgesia but diamorphine is associated with significantly
      longer labours.

PMID- 24289217
TI  - DNA capture and next-generation sequencing can recover whole mitochondrial
      genomes from highly degraded samples for human identification.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) typing can be a useful aid for identifying
      people from compromised samples when nuclear DNA is too damaged, degraded or
      below detection thresholds for routine short tandem repeat (STR)-based analysis.
      Standard mtDNA typing, focused on PCR amplicon sequencing of the control region
      (HVS I and HVS II), is limited by the resolving power of this short sequence,
      which misses up to 70% of the variation present in the mtDNA genome. METHODS: We
      used in-solution hybridisation-based DNA capture (using DNA capture probes
      prepared from modern human mtDNA) to recover mtDNA from post-mortem human remains
      in which the majority of DNA is both highly fragmented (<100 base pairs in
      length) and chemically damaged. The method 'immortalises' the finite quantities
      of DNA in valuable extracts as DNA libraries, which is followed by the targeted
      enrichment of endogenous mtDNA sequences and characterisation by next-generation
      sequencing (NGS). RESULTS: We sequenced whole mitochondrial genomes for human
      identification from samples where standard nuclear STR typing produced only
      partial profiles or demonstrably failed and/or where standard mtDNA hypervariable
      region sequences lacked resolving power. Multiple rounds of enrichment can
      substantially improve coverage and sequencing depth of mtDNA genomes from highly
      degraded samples. The application of this method has led to the reliable
      mitochondrial sequencing of human skeletal remains from unidentified World War
      Two (WWII) casualties approximately 70 years old and from archaeological remains
      (up to 2,500 years old). CONCLUSIONS: This approach has potential applications in
      forensic science, historical human identification cases, archived medical
      samples, kinship analysis and population studies. In particular the methodology
      can be applied to any case, involving human or non-human species, where whole
      mitochondrial genome sequences are required to provide the highest level of
      maternal lineage discrimination. Multiple rounds of in-solution hybridisation
      based DNA capture can retrieve whole mitochondrial genome sequences from even the
      most challenging samples.

PMID- 24289218
TI  - Peripartum cardiomyopathy: ten year experience at a tertiary care hospital in
      Pakistan.
AB  - BACKGROUND: There is very little literature regarding peripartum cardiomyopathy
      from the Asian countries. We conducted this study to determine demographic
      details, clinical presentations, complications and recovery of left ventricular
      (LV) systolic function in peripartum cardiomyopathy (PPCMP) patients of Pakistani
      origin. METHOD: A ten year retrospective case series of PPCMP was conducted at
      the Aga Khan University Hospital. Patients were also followed up for six months
      after presentation, with special regard to improvement in the LV function.
      RESULTS: Total 45 patients were included, 25 (55.5%) primigravida and 8 (17.7%)
      gravida 2 and the remaining 12 (26.6%) were multigravida. Fourteen patients
      (31.1%) presented during pregnancy and 31 (68.8%) after delivery. All patients
      presented with CHF and three (6.6%) were complicated with ventricular tachycardia
      (VT) at presentation. LV systolic dysfunction was present in 39 (86.66%) patients
      and RV dysfunction in 15 (33.3%) patients. Two patients had LV clot and
      thromboembolic stroke occurred in another 4 patients. All patients received
      standard treatment except three patients who had asthma and could not be given
      beta blockers. Echocardiogram was repeated after 6 month and in 32 (71.1%)
      patients LV functions recovered to normal. RV function improved in all except 2
      (4.4%) patients. All patients were discharged in stable condition. CONCLUSION:
      Significant numbers of PPCMP patients, who had severe LV dysfunction at
      presentation recovered their LV functions at six month follow up.

PMID- 24289219
TI  - Effects of combined exercise training on immunological, physical and biochemical
      parameters in individuals with HIV/AIDS.
AB  - The practice of exercise has shown to be beneficial to quality of life of
      individuals with HIV/AIDS. Thus, the present study analysed the effects of a
      combined exercise training in persons living with HIV/AIDS. Ten participants
      participated in the present study. The following variables were analysed: viral
      load and cell counts for TCD4+/TCD8; maximal oxygen consumption (VO2max); total
      mass, absolute fat mass, relative fat mass, absolute lean mass, relative lean
      mass and body mass index; fasting glycaemia, fasting insulinaemia, homeostatic
      model assessment (HOMA) index (insulin resistance - homeostatic model assessment
      (IR-HOMA)); total cholesterol, triglycerides, high-density lipoprotein (HDL),
      very low-density lipoprotein (VLDL), low-density lipoprotein (LDL); superoxide
      dismutase, catalase, glutathione peroxidase activities; thiobarbituric acid
      reactive substances. The combined exercise training consisted of resistance
      exercises plus aerobic training (60 min . session(-1), three times per week,
      during 20 weeks). The number of TCD4+ cells, absolute lean mass and relative lean
      mass, muscle strength for the 45 degrees  leg press, seated row and triceps
      extension, HDL-c levels as well as VO2max increased post-training. The activity
      of superoxide dismutase, catalase, glutathione peroxidase enzymes and
      thiobarbituric acid reactive substances levels were diminished post-training.
      Finally, it can be concluded that combined exercise training is able to change
      positively several variables related to health of individuals with HIV/AIDS,
      mainly the immune system as well as antioxidant mechanisms re-establishment.

PMID- 24289220
TI  - Land-use and land-management change: relationships with earthworm and fungi
      communities and soil structural properties.
AB  - BACKGROUND: Change in land use and management can impact massively on soil
      ecosystems. Ecosystem engineers and other functional biodiversity in soils can be
      influenced directly by such change and this in turn can affect key soil
      functions. Here, we employ meta-analysis to provide a quantitative assessment of
      the effects of changes in land use and land management across a range of
      successional/extensification transitions (conventional arable -> no or reduced
      tillage -> grassland -> wooded land) on community metrics for two functionally
      important soil taxa, earthworms and fungi. An analysis of the relationships
      between community change and soil structural properties was also included.
      RESULTS: Meta-analysis highlighted a consistent trend of increased earthworm and
      fungal community abundances and complexity following transitions to lower
      intensity and later successional land uses. The greatest changes were seen for
      early stage transitions, such as introduction of reduced tillage regimes and
      conversion to grassland from arable land. Not all changes, however, result in
      positive effects on the assessed community metrics. For example, whether woodland
      conversion positively or negatively affects community size and complexity depends
      on woodland type and, potentially, the changes in soil properties, such as pH,
      that may occur during conversion. Alterations in soil communities tended to
      facilitate subsequent changes in soil structure and hydrology. For example,
      increasing earthworm abundances and functional group composition were shown to be
      positively correlated with water infiltration rate (dependent on tillage regime
      and habitat characteristics); while positive changes in fungal biomass measures
      were positively associated with soil microaggregate stability. CONCLUSIONS: These
      findings raise the potential to manage landscapes to increase ecosystem service
      provision from soil biota in relation to regulation of soil structure and water
      flow.

PMID- 24289222
TI  - Researching with young people as participants: issues in recruitment.
AB  - Abstract An essential element of human research is the successful recruitment of
      participants. Many researchers appear to be able to recruit participants quickly
      and without significant issues, while other researchers have more challenges.
      This paper presents some issues encountered when recruiting participants for a
      phenomenological research project on the lived experiences of young people aged
      16-24 years, with type 1 diabetes living in a rural setting. Insights and
      strategies are presented to assist researchers when recruiting young people to
      their research.

PMID- 24289221
TI  - Femtosecond dynamics of short-range protein electron transfer in flavodoxin.
AB  - Intraprotein electron transfer (ET) in flavoproteins is important for
      understanding the correlation of their redox, configuration, and reactivity at
      the active site. Here, we used oxidized flavodoxin as a model system and report
      our complete characterization of a photoinduced redox cycle from the initial
      charge separation in 135-340 fs to subsequent charge recombination in 0.95-1.6 ps
      and to the final cooling relaxation of the product(s) in 2.5-4.3 ps. With 11
      mutations at the active site, we observed that these ultrafast ET dynamics, much
      faster than active-site relaxation, mainly depend on the reduction potentials of
      the electron donors with minor changes caused by mutations, reflecting a highly
      localized ET reaction between the stacked donor and acceptor at a van der Waals
      distance and leading to a gas-phase type of bimolecular ET reaction confined in
      the active-site nanospace. Significantly, these ultrafast ET reactions ensure our
      direct observation of vibrationally excited reaction product(s), suggesting that
      the back ET barrier is effectively reduced because of the decrease in the total
      free energy in the Marcus inverted region, leading to the accelerated charge
      recombination. Such vibrationally coupled charge recombination should be a
      general feature of flavoproteins with similar configurations and interactions
      between the cofactor flavin and neighboring aromatic residues. 

PMID- 24289223
TI  - Rheological changes and kinetics of water uptake by poly(ionic liquid)-based thin
      films.
AB  - Water uptake by thin films composed of the poly(ionic liquid)
      poly[diallyldimethylammonium bis(trifluoromethanesulfonyl)imide] (PDDATf2N) and
      the ionic liquid N,N-butylmethylpyrrolidinium bis(trifluoromethanesulfonyl)imide
      (Pyr1.4Tf2N) was studied with a quartz crystal microbalance with dissipation. The
      data obtained for films with different compositions during the passage of dry and
      wet N2 flow through the films were simulated with the Kevin-Voigt viscoelastic
      model for assessment of the mass of uptake water as well as the viscoelastic
      parameters. Our results show that the ionic liquid acts as a plasticizer,
      reducing the rigidity of the film and decreasing the capacity of water uptake.
      Introduction to a Li salt (LiTf2N) increases the water uptake capacity and also
      affects both elastic and viscous parameters due to aggregation among the ions
      from the ionic liquid and Li(+). However, due to the preferable interaction of
      Li(+) ions with water molecules, these aggregates are broken when the film is
      hydrated. In short, the presence of water in such films affects their mechanical
      properties, which can reflect in their performances as solid state electrolytes
      and ion-conducting membranes for electrochemical applications. 

PMID- 24289224
TI  - The relationship between pruritus and the clinical signs of psoriasis in patients
      receiving tofacitinib.
AB  - OBJECTIVE: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated
      for psoriasis. This study assessed the relationship between pruritus and clinical
      signs of psoriasis (assessed by Physician's Global Assessment [PGA]) in patients
      with moderate-to-severe chronic plaque psoriasis receiving tofacitinib. METHODS:
      In this 16-week (12-week treatment period, 4-week observation period), double
      blind, placebo-controlled, phase IIb study (NCT00678210), 197 patients were
      randomized to tofacitinib 2, 5 or 15 mg BID, or placebo. Pruritus was patient
      assessed using the Itch Severity Score (ISS), a 0-10 (10=worst itching) rating
      scale recorded daily from baseline to week 2 and at study visits. Mediation
      modeling was used to determine relationships between ISS (average score weeks 2
      12), PGA (average score weeks 2-12) and treatment groups. RESULTS: Mediation
      analysis showed that 70.2-80.5% (p<0.001 versus placebo) of tofacitinib's effect
      on pruritus was direct, and mostly independent of improvements in erythema,
      induration and scaling. ISS measurements had acceptable test-retest reliability.
      Correlation analyses with clinical outcomes supported the validity of the ISS as
      a pruritus measure. CONCLUSIONS: Tofacitinib has a direct, beneficial effect on
      patient-reported pruritus independent from improvements in clinician-reported
      psoriasis severity signs. The ISS demonstrated favorable psychometric
      characteristics, supporting its use as a pruritus assessment tool.

PMID- 24289225
TI  - Acute chorea in a child receiving second dose of human papilloma virus vaccine.

PMID- 24289226
TI  - Exploring cultural differences in feedback processes and perceived
      instructiveness during clerkships: replicating a Dutch study in Indonesia.
AB  - CONTEXT: Cultural differences between countries may entail differences in
      feedback processes. AIMS: By replicating a Dutch study in Indonesia, we analysed
      whether differences in processes influenced the perceived instructiveness of
      feedback. METHODS: Over a two-week period, Indonesian students (n = 215) recorded
      feedback moments during clerkships, noting who provided the feedback, whether the
      feedback was based on observations, who initiated the feedback, and its perceived
      instructiveness. Data were compared with the earlier Dutch study and analysed
      with chi(2) tests, t-tests and multilevel techniques. Cultural differences were
      explored using Hofstede's Model, with Indonesia and the Netherlands differing on
      "power distance" and "individualism." RESULTS: Perceived instructiveness of
      feedback did not differ significantly between both countries. However,
      significant differences were found in feedback provider, observation and
      initiative. Indonesian students perceived feedback as more instructive if
      provided by specialists and initiated jointly by the supervisor and student
      (betaresidents = -0.201, p < 0.001 and betajoint = 0.193, p = 0.001). Dutch
      students appreciated feedback more when it was based on observation. CONCLUSIONS:
      We obtained empirical evidence that one model of feedback does not necessarily
      translate to another culture. Further research is necessary to unravel other
      possible influences of culture in implementing feedback procedures in different
      countries.

PMID- 24289227
TI  - Effect of breastfeeding promotion interventions on cost-effectiveness of
      rotavirus immunization in Indonesia.
AB  - BACKGROUND: Rotavirus infection has been reported to be responsible for the
      majority of severe diarrhea in children under-5-years-old in Indonesia. Breast
      milk is considered to give protection against rotavirus infection. Increasing
      breastfeeding promotion programs could be an alternative target to reduce the
      incidence of rotavirus diarrhea. This study aims to investigate the effect of
      breastfeeding promotion interventions on cost-effectiveness of rotavirus
      immunization in Indonesia, focusing on breastfeeding education and support
      interventions. METHODS: An age-structured cohort model was developed for the 2011
      Indonesia birth cohort. We compared four interventions in scenarios: (i) base
      case (I0) reflecting the current situation for the population of under-5-years
      old, (ii) with an additional breastfeeding education intervention (I1), (iii)
      with a support intervention on initiation and duration (I2) and (iv) with both of
      these two interventions combined (I3). The model applied a 5-years time horizon,
      with 1 month analytical cycles for children less than 1 year of age and annually
      thereafter. Monte Carlo simulations were used to examine the economic
      acceptability and affordability of rotavirus vaccination. RESULTS: Rotavirus
      immunization would effectively reduce severe cases of rotavirus during the first
      5 years of a child's life even assuming various breastfeeding promotion
      interventions. The total yearly vaccine cost would amount to US$ 64 million under
      the market vaccine price. Cost-effectiveness would increase to US$ 153 per
      quality-adjusted-life-year (societal perspective) with an optimal breastfeeding
      promotion intervention. Obviously, this is much lower than the 2011 Gross
      Domestic Product (GDP) per capita of US$ 3,495. Affordability results showed that
      at the market vaccine price, rotavirus vaccination could be affordable for the
      Indonesian health system. CONCLUSIONS: Rotavirus immunization would be a highly
      cost-effective public health intervention for Indonesia even under various
      breastfeeding promotion interventions based on the WHO's criteria for cost
      effectiveness in universal immunization.

PMID- 24289228
TI  - Sharing chemical relationships does not reveal structures.
AB  - In this study, we propose a new, secure method of sharing useful chemical
      information from small-molecule libraries, without revealing the structures of
      the libraries' molecules. Our method shares the relationship between molecules
      rather than structural descriptors. This is an important advance because, over
      the past few years, several groups have developed and published new methods of
      analyzing small-molecule screening data. These methods include advanced hit
      picking protocols, promiscuous active filters, economic optimization algorithms,
      and screening visualizations, which can identify patterns in the data that might
      otherwise be overlooked. Application of these methods to private data requires
      finding strategies for sharing useful chemical data without revealing chemical
      structures. This problem has been examined in the context of ADME prediction
      models, with results from information theory suggesting it is impossible to share
      useful chemical information without revealing structures. In contrast, we present
      a new strategy for encoding the relationships between molecules instead of their
      structures, based on anonymized scaffold networks and trees, that safely shares
      enough chemical information to be useful in analyzing chemical data, while also
      sufficiently blinding structures from discovery. We present the details of this
      encoding, an analysis of the usefulness of the information it conveys, and the
      security of the structures it encodes. This approach makes it possible to share
      data across institutions, and may securely enable collaborative analysis that can
      yield insight into both specific projects and screening technology as a whole. 

PMID- 24289229
TI  - Breast cancers with high DSS1 expression that potentially maintains BRCA2
      stability have poor prognosis in the relapse-free survival.
AB  - BACKGROUND: Genetic BRCA2 insufficiency is associated with breast cancer
      development; however, in sporadic breast cancer cases, high BRCA2 expression is
      paradoxically correlated with poor prognosis. Because DSS1, a mammalian component
      of the transcription/RNA export complex, is known to stabilize BRCA2, we
      investigated how the expression of DSS1 is associated with clinical parameters in
      breast cancers. METHODS: DSS1 mRNA and p53 protein were examined by RT-PCR and
      immunohistochemical staining of breast cancer specimens to classify DSS1(high)
      and DSS1(low) or p53(high) and p53(low) groups. Patient survival was compared
      using Kaplan-Meier method. DSS1(high) or DSS1(low) breast cancer cells were
      prepared by retroviral cDNA transfection or DSS1 siRNA on proliferation, cell
      cycle progression, and survival by flow cytometric analyses with or without anti
      cancer drugs. RESULTS: In comparison to patients with low levels of DSS1, high
      DSS1 patients showed a poorer prognosis, with respect to relapse-free survival
      period. The effect of DSS1 was examined in breast cancer cells in vitro. DSS1
      high-expression reduces the susceptibility of MCF7 cells to DNA-damaging drugs,
      as observed in cell cycle and apoptosis analyses. DSS1 knockdown, however,
      increased the susceptibility to the DNA-damaging drugs camptothecin and etoposide
      and caused early apoptosis in p53 wild type MCF7 and p53-insufficient MDA-MB-231
      cells. DSS1 knockdown suppresses the proliferation of drug-resistant MDA-MB-231
      breast cancer cells, particularly effectively in combination with DNA-damaging
      agents. CONCLUSION: Breast cancers with high DSS1 expression have worse prognosis
      and shorter relapse-free survival times. DSS1 is necessary to rescue cells from
      DNA damage, but high DSS1 expression increases drug resistance. We suggest that
      DSS1 expression could be a useful marker for drug resistance in breast cancers,
      and DSS1 knockdown can induce tumor apoptosis when used in combination with DNA
      damaging drugs.

PMID- 24289231
TI  - Knowledge brokers, companions, and navigators: a qualitative examination of
      informal caregivers' roles in medical tourism.
AB  - INTRODUCTION: Many studies examining the phenomena of medical tourism have
      identified health equity issues associated with this global health services
      practice. However, there is a notable lack of attention in this existing research
      to the informal care provided by the friends and family members who typically
      accompany medical tourists abroad. To date, researchers have not examined the
      care roles filled by informal caregivers travelling with medical tourists. In
      this article, we fill this gap by examining these informal caregivers and the
      roles they take on towards supporting medical tourists' health and wellbeing.
      METHODS: We conducted 21 interviews with International Patient Coordinators
      (IPCs) working at medical tourism hospitals across ten countries. IPCs work
      closely with informal caregivers as providers of non-medical personal assistance,
      and can therefore offer broad insight on caregiver roles. The interviews were
      coded and analyzed thematically. RESULTS: Three roles emerged: knowledge broker,
      companion, and navigator. As knowledge brokers, caregivers facilitate the
      transfer of information between the medical tourist and formal health care
      providers as well as other staff members at medical tourism facilities. The
      companion role involves providing medical tourists with physical and emotional
      care. Meanwhile, responsibilities associated with handling documents and
      coordinating often complex journeys are part of the navigation role. CONCLUSIONS:
      This is the first study to examine informal caregiving roles in medical tourism.
      Many of the roles identified are similar to those of conventional informal
      caregivers while others are specific to the transnational context. We conclude
      that these roles make informal caregivers an integral part of the larger
      phenomenon of medical tourism. We further contend that examining the roles taken
      on by a heretofore-unconsidered medical tourism stakeholder group sheds valuable
      insight into how this industry operates and that such knowledge is necessary in
      order to respond to the health equity debates that surround this particular
      global health services practice.

PMID- 24289232
TI  - Reliability of team-based self-monitoring in critical events: a pilot study.
AB  - BACKGROUND: Teamwork is a critical component during critical events. Assessment
      is mandatory for remediation and to target training programmes for observed
      performance gaps. METHODS: The primary purpose was to test the feasibility of
      team-based self-monitoring of crisis resource management with a validated
      teamwork assessment tool. A secondary purpose was to assess item-specific
      reliability and content validity in order to develop a modified context-optimised
      assessment tool.We conducted a prospective, single-centre study to assess team
      based self-monitoring of teamwork after in-situ inter-professional simulated
      critical events by comparison with an assessment by observers. The Mayo High
      Performance Teamwork Scale (MHPTS) was used as the assessment tool with
      evaluation of internal consistency, item-specific consensus estimates for
      agreement between participating teams and observers, and content validity.
      RESULTS: 105 participants and 58 observers completed the MHPTS after a total of
      16 simulated critical events over 8 months. Summative internal consistency of the
      MHPTS calculated as Cronbach's alpha was acceptable with 0.712 for observers and
      0.710 for participants. Overall consensus estimates for dichotomous data
      (agreement/non-agreement) was 0.62 (Cohen's kappa; IQ-range 0.31-0.87). 6/16
      items had excellent (kappa > 0.8) and 3/16 good reliability (kappa > 0.6). Short
      questions concerning easy to observe behaviours were more likely to be reliable.
      The MHPTS was modified using a threshold for good reliability of kappa > 0.6. The
      result is a 9 item self-assessment tool (TeamMonitor) with a calculated median
      kappa of 0.86 (IQ-range: 0.67-1.0) and good content validity. CONCLUSIONS: Team
      based self-monitoring with the MHPTS to assess team performance during simulated
      critical events is feasible. A context-based modification of the tool is
      achievable with good internal consistency and content validity. Further studies
      are needed to investigate if team-based self-monitoring may be used as part of a
      programme of assessment to target training programmes for observed performance
      gaps.

PMID- 24289230
TI  - Optimal dosing of antibiotics in critically ill patients by using
      continuous/extended infusions: a systematic review and meta-analysis.
AB  - INTRODUCTION: The aim of this study was to determine whether using
      pharmacodynamic-based dosing of antimicrobials, such as extended/continuous
      infusions, in critically ill patients is associated with improved outcomes as
      compared with traditional dosing methods. METHODS: We searched Medline,
      HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception
      to September 2013 without language restrictions for studies comparing the use of
      extended/continuous infusions with traditional dosing. Two authors independently
      selected studies, extracted data on methodology and outcomes, and performed
      quality assessment. Meta-analyses were performed by using random-effects models.
      RESULTS: Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782
      patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria.
      Compared with traditional non-pharmacodynamic-based dosing, RCTs of
      continuous/extended infusions significantly reduced clinical failure rates
      (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02)
      and intensive care unit length of stay (mean difference, -1.5; 95% CI, -2.8 to 
      0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P =
      0.38). No significant between-trial heterogeneity was found for these analyses
      (I2 = 0). Reduced mortality rates almost achieved statistical significance when
      the results of all included studies (RCTs and cohort studies) were pooled (RR,
      0.83; 95% CI, 0.69 to 1.00; P = 0.054). CONCLUSIONS: Pooled results from small
      RCTs suggest reduced clinical failure rates and intensive care unit length-of
      stay when using continuous/extended infusions of antibiotics in critically ill
      patients. Reduced mortality rates almost achieved statistical significance when
      the results of RCTs were combined with cohort studies. These results support the
      conduct of adequately powered RCTs to define better the utility of
      continuous/extended infusions in the era of antibiotic resistance.

PMID- 24289233
TI  - The prognosis of patients with lung cancer admitted to the medical intensive care
      unit.
AB  - AIMS: Lung cancer remains the leading cause of cancer mortality worldwide.
      Despite their poor prognosis, patients with lung cancer are increasingly being
      admitted to the medical intensive care unit (MICU) for treatment of critical
      illnesses. The aim of this study was to assess the outcome of patients with lung
      cancer who are admitted to an MICU and to identify the measurable predictors of
      their MICU outcome. METHODS: We conducted retrospective analysis on 97 patients
      with lung cancer admitted to the MICU between 2007 and 2011. RESULTS: The mean
      age +/- standard deviation was 71.8 +/- 6.8 years. Of the 97 patients (82 male),
      73 patients (75%) had non-small cell lung cancer stage IIIB, IV and 24 patients
      (25%) had small cell lung cancer. The intensive care unit mortality and in
      hospital mortality rates were 53.6 and 61.8%. The main reasons for MICU admission
      were pneumonia (n = 51) and complication of cancer management (n = 45). The
      predictors of poor MICU outcome were history of diabetes mellitus (P = 0.028),
      Acute Physiology and Chronic Health Evaluation II score (P = 0.018), need for
      mechanical ventilation (P = 0.014), use of vasoactive agents (P < 0.0001), the
      presence of acute renal failure (P < 0.0001) and presence of multiorgan failure
      (P < 0.0001). CONCLUSIONS: We found that in-hospital mortality was not influenced
      by age, sex or performance status score of patients with lung cancer but
      increased with the severity of organ failure at MICU admission.

PMID- 24289234
TI  - The relationship between lingual and hypoglossal nerve function and quality of
      life in head and neck cancer.
AB  - Sensorimotor impairment of the tongue has the potential to affect speech and
      swallowing. The purpose of this study was to critically examine the effects of
      nerve preservation and reinnervation after reconstruction of the base of tongue
      on patient-perceived outcomes of quality of life (QoL) related to speech and
      swallowing through completion of the EORTC QLQ-H&N35 standardised questionnaire.
      Thirty participants with a diagnosis of base of tongue cancer underwent primary
      resection and reconstruction with a radial forearm free flap, which may or may
      not have included nerve repair to the lingual nerve, hypoglossal nerve or both.
      Eight QoL domains sensitive to changes in motor and sensory nerve function were
      included in the analysis. Transected lingual and hypoglossal nerves were
      associated with difficulty in swallowing, social eating, dry mouth and social
      contact. There were fewer problems reported when these nerves were either
      repaired or left intact. There were no significant differences between patient
      nerve status and QoL outcomes for speech, sticky saliva and use of feeding tubes.
      This study was the first to examine the impact of sensory or motor nerve
      transection and reconstruction on health-related QoL outcomes.

PMID- 24289235
TI  - Influence of hole shape/size on the growth of site-selective quantum dots.
AB  - : The number of quantum dots which nucleate at a certain place has to be
      controllable for device integration. It was shown that the number of quantum dots
      per nucleation site depends on the size of the hole in the substrate, but other
      dimensions of the nucleation site are vague. We report on the influence of hole
      shape on site-selectively grown InAs quantum dots (QDs) by molecular beam
      epitaxy. Dry etching of the GaAs wafers was used because of its high anisotropic
      etching characteristic. Therefore, it was possible to verify the influence of
      several hole shape parameters on the subsequent QD growth independently. We show
      that the nucleation of these QDs depends on several properties of the hole,
      namely its surface area, aspect ratio of the surface area, and depth. Especially,
      the aspect ratio shows a big influence on the number of nucleating QDs per site.
      With knowledge of these dependencies, it is possible to influence the number of
      QDs per site and also its distribution. 

PMID- 24289236
TI  - A study on ovine pneumonic pasteurellosis: isolation and identification of
      Pasteurellae and their antibiogram susceptibility pattern in Haramaya District,
      Eastern Hararghe, Ethiopia.
AB  - BACKGROUND: Sheep constitute the second major component of livestock in Ethiopia.
      However, efficient utilization of this potential resource is hampered by
      combination of health problems, poor management and feed shortage. Haramaya
      district is one of the remote settings in Ethiopia where information about the
      livestock disease is not well documented. Hence this study was conducted to
      determine the causative agents and their antimicrobial susceptibility pattern of
      bacterial Pasteurella isolates among pneumonic ovine in Haramaya district,
      Eastern Hararghe, Ethiopia. RESULTS: Out of 256 samples examined, Pasteurella was
      isolated in 64 (25%), of which 38 (59.4%) were from lungs and 26 (40.6%) were
      from nasal cavities. 87.5% of the isolates were Mannheimia haemolytica and 12.5%
      were Pasteurella multocida. All of the isolates from the lungs were Mannheimia
      haemolytica whereas 69% of the isolates from nasals cavities were Mannheimia
      haemolytica. Age and body temperature were significantly associated with
      Pasteurella isolates from clinic (P < 0.05). Despite diverse in the site of
      origins, the isolates exhibited uniformity in sensitivity to a majority of the
      antibacterial agents. The most effective drug was Cholramphenicol (100%) followed
      by Sulfamethoxazole (89.1%) and Tetracycline (84.4%). Both species were
      completely resistant to Gentamycin and Vancomycin. CONCLUSION: Mannheimia
      haemolytica is the most common cause of ovine pneumonic pasteurellosis in the
      study area. The isolates were susceptible to limited antimicrobial agents.
      Therefore, the antimicrobial susceptibility test should be conducted before
      treatment, except for critical cases.

PMID- 24289238
TI  - Angiotensin II receptor antagonists in acute coronary syndromes.
AB  - BACKGROUND: It is well known that inappropriate or exaggerated activity of the
      renin-angiotensin system might contribute to the development of systemic
      hypertension with consequent organ injury and associated increased risk of acute
      cardiovascular (CV) diseases. This review will discuss evidence form basic
      research and clinical studies, investigating the efficacy of angiotensin II
      receptor blockers (ARBs) in the management of acute coronary syndromes (ACS).
      MATERIALS AND METHODS: This narrative review is based on the material found on
      MEDLINE and PubMed up to June 2013. We looked for the terms 'angiotensin, AT1
      receptor, ACE inhibitors' in combination with 'acute coronary syndromes, acute
      myocardial infarction, pathophysiology'. RESULTS: Preclinical studies showed
      relevant protective effects of ARBs to reduce adverse cardiac remodelling in
      animal models of acute cardiac ischaemia. However, although recommended in
      Consensus guidelines as a good alternative to angiotensin-converting enzyme
      inhibitors (ACEIs), clinical studies did not confirm a superior efficacy of the
      ARBs as compared to ACEIs. As a matter of fact for some authors, these drugs
      might potentially have deleterious effects increasing the CV risk. CONCLUSIONS:
      Emerging evidence from clinical trials suggests that the use of ARBs in ACS might
      be controversial, and caution should be used for their clinical use to replace
      ACEIs in ACS.

PMID- 24289239
TI  - Early application of percutaneous vertebroplasty reduces pain without affecting
      peripheral blood stem cell (PBSC) collection and transplant in newly diagnosed
      multiple myeloma (MM) patients.
AB  - Vertebral fractures occur in over 60% of newly diagnosed multiple myeloma (MM)
      patients and can cause pain, disability and poor quality of life. Antimyeloma
      therapy can lead to symptoms improvement, but these effects can take time to be
      perceived. Application of radiotherapy prior to peripheral blood stem cells
      (PBSC) mobilisation can impair stem cell collection. Percutaneous vertebroplasty
      has been proposed as a suitable option to rapidly relieve bone pain from
      vertebral fractures in MM patients, but, little is known about the effects of
      this procedure on subsequent PBSC mobilisation, collection and transplant.
      Eighteen patients (10M/8F, median age 64.5 years) with untreated MM and painful
      vertebral lesions underwent vertebroplasty prior to proceed to the planned
      transplant program at our Institution. Forty-one procedures were performed at C2
      L5 levels, eight patients were treated at >=2 levels. Ninety-five per cent of the
      cases obtained a complete or optimal pain control. All the patients successfully
      mobilised PBSC (median CD34+ cells = 10.8 * 10(6) /kg) and underwent autologous
      PBSC transplant; both polymorphonucleates and platelets recovery averaged 11
      days. Our data seem to suggest that percutaneous vertebroplasty is useful in
      newly diagnosed MM patients with painful vertebral fractures as it allows rapid
      and durable achievement of pain control, without interfering with further
      treatment. 

PMID- 24289240
TI  - Does aspartic acid racemization constrain the depth limit of the subsurface
      biosphere?
AB  - Previous studies of the subsurface biosphere have deduced average cellular
      doubling times of hundreds to thousands of years based upon geochemical models.
      We have directly constrained the in situ average cellular protein turnover or
      doubling times for metabolically active micro-organisms based on cellular amino
      acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic
      acid racemization rate. Application of this method to planktonic microbial
      communities collected from deep fractures in South Africa yielded maximum
      cellular amino acid turnover times of ~89 years for 1 km depth and 27  degrees C
      and 1-2 years for 3 km depth and 54  degrees C. The latter turnover times are
      much shorter than previously estimated cellular turnover times based upon
      geochemical arguments. The aspartic acid racemization rate at higher temperatures
      yields cellular protein doubling times that are consistent with the survival
      times of hyperthermophilic strains and predicts that at temperatures of 85 
      degrees C, cells must replace proteins every couple of days to maintain enzymatic
      activity. Such a high maintenance requirement may be the principal limit on the
      abundance of living micro-organisms in the deep, hot subsurface biosphere, as
      well as a potential limit on their activity. The measurement of the D/L of
      aspartic acid in biological samples is a potentially powerful tool for deep,
      fractured continental and oceanic crustal settings where geochemical models of
      carbon turnover times are poorly constrained. Experimental observations on the
      racemization rates of aspartic acid in living thermophiles and hyperthermophiles
      could test this hypothesis. The development of corrections for cell wall peptides
      and spores will be required, however, to improve the accuracy of these estimates
      for environmental samples. 

PMID- 24289242
TI  - Diagnostic accuracy of 64-MDCT angiography in the preoperative evaluation of
      renal vessels and compared with laparotomy findings in living donor kidney.
AB  - INTRODUCTION: Multidetector-row computed tomography (MDCT) angiography is a
      reliable technique in preoperative renal anatomy evaluation in live renal donors.
      OBJECTIVES: To investigate the accuracy of early arterial phase findings and
      compares them with intraoperative findings. METHODS: In this prospective study,
      100 potential live donors undergoing preoperative MDCT and nephrectomy during
      2010-2013 were included. The examination was performed with a 64-detector scanner
      including early arterial and venous phase. MDCT angiography started by bolus
      tracking and venous phase was acquired 9 s after arterial phase. Anatomical
      findings and vein and artery attenuation values were recorded and arterial phase
      findings were compared with intraoperative findings. RESULTS: All anatomical
      findings reported by MDCT in early arterial phase were confirmed by
      intraoperative findings with sensitivity of 100%. Right renal vein was
      supernumerary in 17 cases and left renal vein was circumaortic in 3 and
      retroaortic in 5 cases. Renal arteries had early branching in 13, two arteries in
      12 and accessory in 8 cases. Vein and artery attenuation values had significant
      difference between early arterial and venous phase (p < 0.001). CONCLUSION: Early
      arterial phase has similar results to venous phase in preoperative evaluation and
      intraoperative findings and could be used alone to reduce radiation dose.

PMID- 24289241
TI  - Embryonic neurogenesis in Pseudopallene sp. (Arthropoda, Pycnogonida) includes
      two subsequent phases with similarities to different arthropod groups.
AB  - BACKGROUND: Studies on early neurogenesis have had considerable impact on the
      discussion of the phylogenetic relationships of arthropods, having revealed
      striking similarities and differences between the major lineages. In Hexapoda and
      crustaceans, neurogenesis involves the neuroblast, a type of neural stem cell. In
      each hemi-segment, a set of neuroblasts produces neural cells by repeated
      asymmetrical and interiorly directed divisions. In Euchelicerata and Myriapoda,
      neurogenesis lacks neural stem cells, featuring instead direct immigration of
      neural cell groups from fixed sites in the neuroectoderm. Accordingly, neural
      stem cells were hitherto assumed to be an evolutionary novelty of the Tetraconata
      (Hexapoda + crustaceans). To further test this hypothesis, we investigated
      neurogenesis in Pycnogonida, or sea spiders, a group of marine arthropods with
      close affinities to euchelicerates. RESULTS: We studied neurogenesis during
      embryonic development of Pseudopallene sp. (Callipallenidae), using fluorescent
      histochemical staining and immunolabelling. Embryonic neurogenesis has two
      phases. The first phase shows notable similarities to euchelicerates and
      myriapods. These include i) the lack of morphologically different cell types in
      the neuroectoderm; ii) the formation of transiently identifiable, stereotypically
      arranged cell internalization sites; iii) immigration of predominantly post
      mitotic ganglion cells; and iv) restriction of tangentially oriented cell
      proliferation to the apical cell layer. However, in the second phase, the
      formation of a central invagination in each hemi-neuromere is accompanied by the
      differentiation of apical neural stem cells. The latter grow in size, show high
      mitotic activity and an asymmetrical division mode. A marked increase of ganglion
      cell numbers follows their differentiation. Directly basal to the neural stem
      cells, an additional type of intermediate neural precursor is found. CONCLUSIONS:
      Embryonic neurogenesis of Pseudopallene sp. combines features of central nervous
      system development that have been hitherto described separately in different
      arthropod taxa. The two-phase character of pycnogonid neurogenesis calls for a
      thorough reinvestigation of other non-model arthropods over the entire course of
      neurogenesis. With the currently available data, a common origin of pycnogonid
      neural stem cells and tetraconate neuroblasts remains unresolved. To acknowledge
      this, we present two possible scenarios on the evolution of arthropod
      neurogenesis, whereby Myriapoda play a key role in the resolution of this issue.

PMID- 24289243
TI  - Array data extractor (ADE): a LabVIEW program to extract and merge gene array
      data.
AB  - BACKGROUND: Large data sets from gene expression array studies are publicly
      available offering information highly valuable for research across many
      disciplines ranging from fundamental to clinical research. Highly advanced
      bioinformatics tools have been made available to researchers, but a demand for
      user-friendly software allowing researchers to quickly extract expression
      information for multiple genes from multiple studies persists. FINDINGS: Here, we
      present a user-friendly LabVIEW program to automatically extract gene expression
      data for a list of genes from multiple normalized microarray datasets.
      Functionality was tested for 288 class A G protein-coupled receptors (GPCRs) and
      expression data from 12 studies comparing normal and diseased human hearts.
      Results confirmed known regulation of a beta 1 adrenergic receptor and further
      indicate novel research targets. CONCLUSIONS: Although existing software allows
      for complex data analyses, the LabVIEW based program presented here, "Array Data
      Extractor (ADE)", provides users with a tool to retrieve meaningful information
      from multiple normalized gene expression datasets in a fast and easy way.
      Further, the graphical programming language used in LabVIEW allows applying
      changes to the program without the need of advanced programming knowledge.

PMID- 24289244
TI  - A comparative study of low-fluence 1064-nm Q-switched Nd:YAG laser with or
      without chemical peeling using Jessner's solution in melasma patients.
AB  - BACKGROUND: Although low-fluence 1064-nm Q-switched Nd:YAG laser (QSNYL) is
      widely used for the treatment of melasma, multiple treatments are necessary for
      clinical improvement. Superficial chemical peeling using Jessner's solution has
      been used for treatment of melasma conventionally. OBJECTIVES: To evaluate the
      additional therapeutic effect and adverse effects of Jessner's peel when combined
      with 1064-nm QSNYL for melasma patients in a double-blind, placebo-controlled
      design. METHODS: Total of 52 patients were included. Patients who received 10
      sessions of 1064-nm QSNYL plus chemical peeling with placebo (group A) in a two
      week interval and those who received 10 sessions of 1064-nm QSNYL plus chemical
      peeling with Jessner's solution (group B) in a two-week interval were analyzed.
      Responses were evaluated using the Melasma Area and Severity Index (MASI) score,
      physician's global assessment (PGA) and subjective self-assessment. RESULTS: At 8
      weeks, the mean MASI score decreased from 8.68 +/- 4.06 to 8.60 +/- 3.88 in group
      A and from 8.98 +/- 3.72 to 7.13 +/- 2.57 in group B, showing a significant
      difference (p < 0.001). But at 20 weeks, there was no significant difference on
      reduction of MASI, self-assessment and PGA between the two groups. No serious
      adverse effects were reported with the additional Jessner's peeling. CONCLUSION:
      This study suggests Jessner's peel is a safe and effective method in the early
      course of treatment for melasma when combined with low-fluence 1064-nm Q-switched
      Nd:YAG laser.

PMID- 24289245
TI  - Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined
      pituitary hormone deficiency.
AB  - BACKGROUND: The complex process of development of the pituitary gland is
      regulated by a number of signalling molecules and transcription factors.
      Mutations in these factors have been identified in rare cases of congenital
      hypopituitarism but for most subjects with combined pituitary hormone deficiency
      (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect
      induction and growth of the pituitary primordium and thus represent plausible
      candidates for mutational screening of patients with CPHD. METHODS: We sequenced
      BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic
      variants were genotyped in 1046 healthy subjects. Additionally, potential
      functional relevance for most promising variants has been assessed by
      phylogenetic analyses and prediction of effects on protein structure. RESULTS:
      Sequencing revealed two novel variants and confirmed 30 previously known
      polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses
      indicated that these variants map within strongly conserved gene regions, there
      was no direct support for their impact on protein structure when applying
      predictive bioinformatics tools. CONCLUSIONS: A mutation in the BMP4 coding
      region resulting in an amino acid exchange (p.Arg300Pro) appeared most
      interesting among the identified variants. Further functional analyses are
      required to ultimately map the relevance of these novel variants in CPHD.

PMID- 24289247
TI  - Preparation and self-assembly behavior of beta-sheet peptide-inserted amphiphilic
      block copolymer as a useful polymeric surfactant.
AB  - A hybridization of structurally regulated biopolymers and conventional synthetic
      polymers offers promising opportunities to design novel polymeric nanomaterials.
      In this study, we newly prepared an amphiphilic triblock copolymer with beta
      sheet forming peptide as a central block, polystyrene-block-tetra(leucine)-block
      poly(ethylene glycol) (PS-L4-PEG), by combining the solid phase peptide synthesis
      with the atom transfer radical polymerization (ATRP). On the basis of several
      morphological and structural analyses using atomic force microscopy, transmission
      electron microscopy, FTIR spectroscopy, and contact angle measurement, the PS-L4
      PEG was found to form PEG-shell spherical and/or elliptical vesicles with a
      diameter of 30-100 nm in aqueous medium. By contrast, the PS-L4-PEG self
      assembled into PS-shell spherical aggregates in toluene, which is good solvent
      for both PEG and PS. In both cases, the central peptide formed a beta-sheet
      network in the nanoassemblies. Furthermore, the PS-L4-PEG was found to stabilize
      a water-in-oil emulsion remarkably in comparison with the PS-PEG diblock
      copolymer, demonstrating the potential of this peptide-polymer hybrid as a useful
      polymeric surfactant. 

PMID- 24289246
TI  - FGF-FGFR signaling mediated through glycosaminoglycans in microtiter plate and
      cell-based microarray platforms.
AB  - Fibroblast growth factor (FGF) signals cell growth through its interaction with a
      fibroblast growth factor receptor (FGFR) and a glycosaminoglycn (GAG) coreceptor.
      Here, we examine the signaling of five different FGFs (1, 2, 6, 8, and 8b)
      through FGFR3c. A small library of GAG and GAG-derivative coreceptors are
      screened to understand better the structure-activity relationship of these
      coreceptors on signaling. Initially, data were collected in a microtiter plate
      well-based cell proliferation assay. In an effort to reduce reagent requirements
      and improve assay throughput, a cell-based microarray platform was developed. In
      this cell-based microarray, FGFR3c-expressing cells were printed in alginate
      hydrogel droplets of ~30 nL and incubated with FGF and GAG. Heparin was the most
      effective GAG coreceptor for all FGFs studied. Other GAGs, such as 2-O-desulfated
      heparin and chondroitin sulfate B, were also effective coreceptors. Signaling by
      FGF 8 and FGF 8b showed the widest tolerance for coreceptor structure. Finally,
      this on-chip cell-based microarray provides comparable data to a microtiter plate
      well-based assay, demonstrating that the coreceptor assay can be converted into a
      high-throughput assay. 

PMID- 24289248
TI  - Environmental factors independently associated with the first episode of wheezing
      among children.

PMID- 24289249
TI  - Classifier ensemble based on feature selection and diversity measures for
      predicting the affinity of A(2B) adenosine receptor antagonists.
AB  - A(2B) adenosine receptor antagonists may be beneficial in treating diseases like
      asthma, diabetes, diabetic retinopathy, and certain cancers. This has stimulated
      research for the development of potent ligands for this subtype, based on
      quantitative structure-affinity relationships. In this work, a new ensemble
      machine learning algorithm is proposed for classification and prediction of the
      ligand-binding affinity of A(2B) adenosine receptor antagonists. This algorithm
      is based on the training of different classifier models with multiple training
      sets (composed of the same compounds but represented by diverse features). The k
      nearest neighbor, decision trees, neural networks, and support vector machines
      were used as single classifiers. To select the base classifiers for combining
      into the ensemble, several diversity measures were employed. The final
      multiclassifier prediction results were computed from the output obtained by
      using a combination of selected base classifiers output, by utilizing different
      mathematical functions including the following: majority vote, maximum and
      average probability. In this work, 10-fold cross- and external validation were
      used. The strategy led to the following results: i) the single classifiers,
      together with previous features selections, resulted in good overall accuracy,
      ii) a comparison between single classifiers, and their combinations in the
      multiclassifier model, showed that using our ensemble gave a better performance
      than the single classifier model, and iii) our multiclassifier model performed
      better than the most widely used multiclassifier models in the literature. The
      results and statistical analysis demonstrated the supremacy of our
      multiclassifier approach for predicting the affinity of A(2B) adenosine receptor
      antagonists, and it can be used to develop other QSAR models.

PMID- 24289250
TI  - Invasively-treated incidence of lower extremity peripheral arterial disease and
      associated factors in Taiwan: 2000-2011 nationwide hospitalized data analysis.
AB  - BACKGROUND: Lower extremity (LE) peripheral artery disease (PAD), which is
      associated with a reduced quality of life and increased mortality from
      atherosclerotic cardio-/cerebro-vascular occlusion, is a significant public
      health problem, especial for an aging society such as that of Taiwan. METHODS:
      Specific datasets of the 2000-2011 nationwide inpatient databases were analyzed.
      Two inclusion criteria, including one of the major diagnosis codes of PAD and one
      of three categorical invasive treatments of LE PAD, were used consecutively to
      select cases diagnosed as LE PAD and receiving invasive treatment. The
      epidemiology of invasively-treated PAD in Taiwan was estimated, and the
      influences of potential confounders on these invasively-treated methods were
      evaluated. RESULTS: In general, the invasively-treated incidence of PAD in Taiwan
      doubled, from 3.73/10,000 (in 2000) to 7.48/10,000 (in 2011). On average, the
      total direct medical cost of one hospitalized and invasively-treated PAD case
      ranged from $US 4,600 to $US 5,900. The annual cases of bypass surgery for the
      PAD cases averaged 1,000 and the cases for limb amputation ranged from 4,100 to
      5,100 annually. However, the number of percutaneous transluminal angioplasty
      (PTA) procedures remarkably increased by 15 times, from 600/year to 9,100/year,
      from 2000 to 2011. 51.3% of all the enrolled cases were treated with limb
      amputations, and female, young and middle-aged people (30-65 years of age), DM
      patients and those on a low income had a tendency to undergo amputation due to
      PAD. 37.6% of all the enrolled cases were treated with PTAs related to
      hypertension, cardiovascular disease, hyperlipidemia and catastrophic Illness. 2
      year PTA failure rates of 22.13%, 11.91% and 10.61% were noted among the first
      (2000-2001), second (2004-2005) and the third (2008-2009) cohort groups,
      respectively. CONCLUSIONS: In Taiwan, a gender difference and age and period
      effects on the invasively-treated incidence of LE PAD were observed. Female,
      young and middle-aged people (30-50 and 50-65 years of age), DM patients and
      those on a low income had a tendency to undergo amputation. The number of PTA
      procedures remarkably increased, but the 2-year failure rate of PTAs reduced from
      2000 to 2011.

PMID- 24289251
TI  - Influence of standardized patient body habitus on undergraduate student
      performance in an Objective Structured Clinical Examination.
AB  - PURPOSE: Previous studies have shown that the standardized patient's (SP) gender
      may affect student performance in an Objective Structured Clinical Examination
      (OSCE). The aim of this study is to investigate the influence of the SPs' body
      habitus on students' performance in an OSCE counseling station. METHODS: Four
      equally trained female SPs, with either a normal or an obese BMI participated in
      an OSCE counseling station for cardiovascular risk factors. Ninety-two, second
      year medical students were randomly assigned to one of the SPs. Station scores
      were compared and student behavior and opinion regarding the influence of their
      SP's body habitus on their performance was assessed. RESULTS: There was no
      difference in mean exam scores for students interacting with SPs with a normal
      BMI versus increased BMI (14.9 +/- 2.2 versus 14.01 +/- 2.2/20 respectively, p =
      0.06). Additionally, almost all students gave advice about healthy diets (93.5%
      versus 95.7%) with no specificity regarding the BMI of the SP. CONCLUSIONS: The
      body habitus of the SP did not significantly affect students' performance in an
      undergraduate OSCE about cardiovascular risk factors, suggesting that students at
      that level may primarily focus on gaining points the diagnostic checklist without
      considering SPs as real patients.

PMID- 24289252
TI  - The novel myxofibrosarcoma cell line MUG-Myx1 expresses a tumourigenic stem-like
      cell population with high aldehyde dehydrogenase 1 activity.
AB  - BACKGROUND: Myxofibrosarcoma comprises a spectrum of malignant neoplasms
      withprominent myxoid stromata, cellular pleomorphism, and distinct curvilinear
      vascular patterns. These neoplasms mainly affect patients in the sixth to eighth
      decades of life and the overall 5-year survival rate is 60-70%. METHODS: After
      the establishment of the novel myxofibrosarcoma cell lines MUG-Myx1, cells were
      characterized using short tandem repeat (STR), copy number variation (CNV), and
      genotype/loss-of-heterozygosity (LOH) analyses. The growth behaviour of the cells
      was analyzed with the xCELLigence system and an MTS assay. The tumourigenicity of
      MUG-Myx1 was proved in NOD/SCID mice. Additionally, a stem-like cell population
      with high enzymatic activity of aldehyde dehydrogenase 1 (ALDH1(high)) was
      isolated for the first time from myxofibrosarcoma cells using the Aldefluor(r)
      assay followed by FACS analysis. RESULTS: The frozen primary parental tumour
      tissue and the MUG-Myx1 cell line showed the same STR profile at the markers
      D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO,
      Penta D, Amelogenin, D8S1179, TPOX, and FGY. Typically, myxofibrosarcoma gain
      and/or amplification was mapped to 7p21.3-q31.1, q31.1-q31.33, q33-q36.2, p21.3,
      p21.2, p14.1-q11.23, q31.33-q33, p21.2-p14.1, q11.23-q21.3, q36.2-q36.3, which,
      respectively are known to harbour tumour-associated genes, including TIF, BRAF,
      MLL3, SMO, and MET. Typically an LOH for myxofibrosarcoma on chr5 q21 was found.
      In addition, MUG-Myx1 ALDH1(high) cells showed an upregulation of the ABC
      transporter ABCB1 and ABCG2; higher c-Myc, E-cadherin and SOX-2 expression; and a
      higher potential for tumourigenicity and proliferation levels. CONCLUSION: The
      new myxofibrosarcoma cell line MUG-Myx1 was established to enrich the bank of
      publicly available cell lines, with respect to providing comprehensive genetic
      and epigenetic characterization. Furthermore, because of their tumourigenicity,
      the cell line is also suitable for in vivo experiments.

PMID- 24289254
TI  - 'Becoming a species by becoming a pest' or how two maize pests of the genus
      Ostrinia possibly evolved through parallel ecological speciation events.
AB  - New agricultural pest species attacking introduced crops may evolve from pre
      existing local herbivores by ecological speciation, thereby becoming a species by
      becoming a pest. We compare the evolutionary pathways by which two maize pests
      (the Asian and the European corn borers, ACB and ECB) in the genus Ostrinia
      (Lepidoptera, Crambidae) probably diverged from an ancestral species close to the
      current Adzuki bean borer (ABB). We typed larval Ostrinia populations collected
      on maize and dicotyledons across China and eastern Siberia, at microsatellite and
      mitochondrial loci. We found only two clusters: one on maize (as expected) and a
      single one on dicotyledons despite differences in male mid-tibia morphology,
      suggesting that all individuals from dicotyledons belonged to the ABB. We found
      evidence for migrants and hybrids on both host plant types. Hybrids suggest that
      field reproductive isolation is incomplete between ACB and ABB. Interestingly, a
      few individuals with an 'ABB-like' microsatellite profile collected on
      dicotyledons had 'ACB' mtDNA rather than 'ABB-like' mtDNA, whereas the reverse
      was never found on maize. This suggests asymmetrical gene flow directed from the
      ACB towards the ABB. Hybrids and backcrosses in all directions were obtained in
      no-choice tests. In laboratory conditions, they survived as well as parental
      strain individuals. In Xinjiang, we found ACB and ECB in sympatry, but no
      hybrids. Altogether, our results suggest that reproductive isolation between ACB
      and ABB is incomplete and mostly prezygotic. This points to ecological speciation
      as a possible evolutionary scenario, as previously found for ECB and ABB in
      Europe.

PMID- 24289253
TI  - Prenatal exposure to cooking gas and respiratory health in infants is modified by
      tobacco smoke exposure and diet in the INMA birth cohort study.
AB  - BACKGROUND: Studies that have evaluated the association between exposure to gas
      appliances emissions at home with respiratory health in children obtained
      heterogeneous and limited results. The aim of this study is to analyze the
      association between the use of gas cooking at home during pregnancy and
      respiratory problems in children during their first year of life. METHODS: In the
      years 2003 through 2008 pregnant women were enrolled in 4 Spanish areas and
      visited in different age-points following a common protocol. Outcomes studied
      (from a questionnaire) were any episode of lower respiratory tract infection
      (LRTI), wheezing, persistent cough, chestiness and otitis. The association
      between exposure to gas cooking at home and respiratory outcomes was assessed
      using logistic regression and adjusting by confounding variables. Some potential
      effect modifiers (i.e. smoking, fruit and vegetables consumption) were examined.
      RESULTS: Among the 2003 children included in the study, a total of 731 (36.6%)
      had a LRTI episode, 693 (34.6%) experienced wheezing, 302 (15.5%) a persistent
      cough, 939 (47.4%) chestiness and 620 (31.2%) had an episode of otitis during
      their first year of life. Gas cookers were present in 45.5% of homes. Exposure to
      gas cooking in homes was not associated with respiratory outcomes Odds Ratios
      (OR) were close to 1 and not statistically significant. However, a positive
      association was found for otitis among infants whose mothers reported low intakes
      of fruit and vegetables during pregnancy [OR (95% CI) = 1.38 (1.01-1.9)] and also
      wheezing and chestiness were associated with gas cookers among those children
      whose mothers smoked during pregnancy. CONCLUSIONS: In susceptible subjects
      (those whose mothers smoke and consumed below average fruit and vegetables) we
      found an association between exposure to gas cooking during pregnancy and risk of
      wheezing, chestiness and otitis during the first year of life. But more research
      is needed regarding not only gas cooking and respiratory health but also the
      possible effect modifier role of diet and tobacco.

PMID- 24289255
TI  - Antireflective grassy surface on glass substrates with self-masked dry etching.
AB  - Although recently developed bio-inspired nanostructures exhibit superior optic
      performance, their practical applications are limited due to cost issues. We
      present highly transparent glasses with grassy surface fabricated with self
      masked dry etch process. Simultaneously generated nanoclusters during reactive
      ion etch process with simple gas mixture (i.e., CF4/O2) enables lithography-free,
      one-step nanostructure fabrication. The resulting grassy surfaces, composed of
      tapered subwavelength structures, exhibit antireflective (AR) properties in 300
      to 1,800-nm wavelength ranges as well as improved hydrophilicity for antifogging.
      Rigorous coupled-wave analysis calculation provides design guidelines for AR
      surface on glass substrates. 

PMID- 24289256
TI  - Surgical resection and long-term survival outcome for non-small cell lung cancer:
      a comparison of Victorian population-based studies spanning a decade.
AB  - AIM: A survey of management of lung cancer diagnosed in Victoria in 2003 was
      commissioned by the Victorian Cooperative Oncology Group to identify gaps in the
      management of this disease. Results from a similar survey in 1993 were available
      to identify differences in the disease, management and outcomes. This paper
      details results of the surgically managed subset within the larger study.
      METHODS: All patients diagnosed with lung cancer in the first 6 months of 2003
      were identified from the Victorian Cancer Registry. Registry research staff
      completed a detailed questionnaire using primary source documents from hospitals
      and consulting rooms. The survey data were then de-identified with respect to
      patient and treating clinician prior to statistical analysis by the
      investigators. RESULTS: From eligible cases identified, non-small cell lung
      cancer was confirmed in 655 cases with a minimum of 6 years of follow-up.
      Thoracotomy was performed in 145 cases (22%), but only 130 received the intended
      resection. Compared with 1993, significant differences were increased use of
      preoperative positron emission tomography (PET) scanning (79% vs 0%), relatively
      fewer resections (20% vs 25%), lower pneumonectomy rate (14% vs 25%) and higher
      sub-lobar resection rate (22% vs 11%). The 30-day mortality remained below 2%.
      Positive resection margin (21%) and abandoned resection rates (10%) were much
      higher than expected. Overall 5-year survival was 42%, unchanged from 1993.
      CONCLUSION: Irrespective of widespread introduction of PET scanning, thoracotomy
      without resection was common. While operative mortality and overall survival were
      well within benchmark standards, futile thoracotomy and positive resection margin
      rates were unacceptably high.

PMID- 24289257
TI  - Adjusting for measurement error in baseline prognostic biomarkers included in a
      time-to-event analysis: a joint modelling approach.
AB  - BACKGROUND: Methodological development of joint models of longitudinal and
      survival data has been rapid in recent years; however, their full potential in
      applied settings are yet to be fully explored. We describe a novel use of a
      specific association structure, linking the two component models through the
      subject specific intercept, and thus extend joint models to account for
      measurement error in a biomarker, even when only the baseline value of the
      biomarker is of interest. This is a common occurrence in registry data sources,
      where often repeated measurements exist but are simply ignored. METHODS: The
      proposed specification is evaluated through simulation and applied to data from
      the General Practice Research Database, investigating the association between
      baseline Systolic Blood Pressure (SBP) and the time-to-stroke in a cohort of
      obese patients with type 2 diabetes mellitus. RESULTS: By directly modelling the
      longitudinal component we reduce bias in the hazard ratio for the effect of
      baseline SBP on the time-to-stroke, showing the large potential to improve on
      previous prognostic models which use only observed baseline biomarker values.
      CONCLUSIONS: The joint modelling of longitudinal and survival data is a valid
      approach to account for measurement error in the analysis of a repeatedly
      measured biomarker and a time-to-event. User friendly Stata software is provided.

PMID- 24289259
TI  - Chromatin signatures at transcriptional start sites separate two equally
      populated yet distinct classes of intergenic long noncoding RNAs.
AB  - BACKGROUND: Mammalian transcriptomes contain thousands of long noncoding RNAs
      (lncRNAs). Some lncRNAs originate from intragenic enhancers which, when active,
      behave as alternative promoters producing transcripts that are processed using
      the canonical signals of their host gene. We have followed up this observation by
      analyzing intergenic lncRNAs to determine the extent to which they might also
      originate from intergenic enhancers. RESULTS: We integrated high-resolution maps
      of transcriptional initiation and transcription to annotate a conservative set of
      intergenic lncRNAs expressed in mouse erythroblasts. We subclassified intergenic
      lncRNAs according to chromatin status at transcriptional initiation regions,
      defined by relative levels of histone H3K4 mono- and trimethylation. These
      transcripts are almost evenly divided between those arising from enhancer
      associated (elncRNA) or promoter-associated (plncRNA) elements. These two classes
      of 5' capped and polyadenylated RNA transcripts are indistinguishable with regard
      to their length, number of exons or transcriptional orientation relative to their
      closest neighboring gene. Nevertheless, elncRNAs are more tissue-restricted, less
      highly expressed and less well conserved during evolution. Of considerable
      interest, we found that expression of elncRNAs, but not plncRNAs, is associated
      with enhanced expression of neighboring protein-coding genes during
      erythropoiesis. CONCLUSIONS: We have determined globally the sites of initiation
      of intergenic lncRNAs in erythroid cells, allowing us to distinguish two
      similarly abundant classes of transcripts. Different correlations between the
      levels of elncRNAs, plncRNAs and expression of neighboring genes suggest that
      functional lncRNAs from the two classes may play contrasting roles in regulating
      the transcript abundance of local or distal loci.

PMID- 24289260
TI  - "Nonmedical" prescription opioid use in North America: a call for priority
      action.
AB  - Nearly four years after the United States Congress heralded a "decade of pain
      control and research", chronic pain remains a mounting public health concern
      worldwide. The escalating prevalence of chronic pain in recent years has been
      paralleled by a rise in prescription opioid availability, misuse, and associated
      human and social costs. However, national monitoring surveys in the U.S. and
      Canada currently fail to differentiate between prescription opioid misuse for the
      purposes of euphoria versus pain or withdrawal management. Furthermore, there is
      a lack of evidence-based guidelines for pain management among high-risk
      individuals, and a glaring lack of education for practitioners in the areas of
      pain and addiction medicine. Herein we propose multiple avenues for intervention
      and research in order to mitigate the individual, social and structural problems
      related to undertreated pain and prescription opioid misuse. 

PMID- 24289258
TI  - Functional imaging in lung cancer.
AB  - Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An
      increasing awareness on smoking cessation as an important mean to reduce lung
      cancer incidence and mortality, an increasing number of therapy options and a
      steady focus on early diagnosis and adequate staging have resulted in a modestly
      improved survival. For early diagnosis and precise staging, imaging, especially
      positron emission tomography combined with CT (PET/CT), plays an important role.
      Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT)
      and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results
      within this field. The purpose of this review is to provide the reader with a
      brief and balanced introduction to these three functional imaging modalities and
      their current or potential application in the care of patients with lung cancer. 

PMID- 24289261
TI  - Is combined use of SSRIs and NSAIDs associated with an increased risk of starting
      peptic ulcer treatment?

PMID- 24289262
TI  - CA 125 levels and left ventricular function in patients with end-stage renal
      disease on maintenance hemodialysis.
AB  - PURPOSE: The aim of this study was to analyze associations between serum cancer
      antigen 125 (CA 125) levels and left ventricular (LV) function in patients with
      end-stage renal disease on maintenance hemodialysis (HD). METHODS: CA 125 levels,
      pro-brain natriuretic peptide (pro-BNP) and biochemical parameters were measured,
      and echocardiography was performed for 110 patients and 47 healthy controls.
      RESULTS: The mean CA 125 level in patients, 38.78 +/- 35.48 U/mL, was
      significantly higher than that found in healthy controls (9.20 +/- 4.55 U/mL; p =
      0.003). Patients with elevated CA 125 levels (n = 40) had significantly lower
      levels of albumin and reduced relative wall thickness, LV ejection fraction (EF)
      and fractional shortening but significantly higher levels of pro-BNP and a
      greater left ventricular end-diastolic diameter (LVEDd) and -systolic diameter
      (LVESd). CA 125 levels were positively correlated with pro-BNP (r = 0.596, p <
      0.05) and C-reactive protein (CRP) levels (r = 0.439, p < 0.05), as well as LVEDd
      (r = 0.599, p < 0.001), LVESd (r = 0.750, p < 0.001) and LV mass index (r =
      0.378, p < 0.05). In contrast, serum CA 125 levels were negatively correlated
      with albumin (r = -0.513, p < 0.05) and hemoglobin (r = -0.475, p < 0.05) as well
      as the EF (r = -0.878, p < 0.0001). A depressed EF (beta = -1.121, p < 0.0001)
      and increased CRP levels (beta = 0.247, p = 0.035) were independent predictors of
      high CA 125 levels in the whole group in the multivariate-model. CONCLUSIONS: Our
      study is the first to demonstrate an association between serum CA 125 levels and
      LV systolic dysfunction via inflammation in patients on maintenance HD.

PMID- 24289264
TI  - Age-specific locomotor response to nicotine in yellow and mottled yellow A(vy)/a
      mice.
AB  - BACKGROUND: Most Agouti viable yellow (Avy) mice display constitutive expression
      of agouti protein, which acts as an inverse agonist at the melanocortin receptor
      4 (Mc4r), resulting in adult-onset obesity as well as an altered sensitivity to
      some drugs of abuse. We investigated the influence of excessive agouti expression
      on open-field locomotor response to daily 0.5 mg/kg (-)-freebase nicotine
      injections in 27 early adolescent and 27 young adult male Avy/a and a/a mice, and
      assessed the effects of nicotine administration (0.5 mg/kg) followed by open
      field testing on serum corticosterone levels in a separate group of 25 young
      adult male Avy/a and a/a mice. FINDINGS: Young adult Avy/a mice displayed
      pronounced nicotine-induced hypolocomotion (a 24% reduction in distance traveled)
      compared to their a/a littermates. Early adolescent Avy/a mice did not differ
      from their a/a littermates or saline-matched controls in locomotion following
      nicotine administration. Young adult Avy/a mice also displayed increased
      thigmotaxis (a 5% increase in time spent outside the center of the apparatus) on
      the first day of nicotine administration as compared to saline-matched controls,
      while a/a mice did not. An increase in serum corticosterone levels 20 minutes
      after nicotine injection in a separate group of young adult male mice (n = 25)
      was proportionally similar between Avy/a and a/a mice. CONCLUSIONS: Overall, the
      results suggest an age- and epigenotype- or genotype-specific response to
      nicotine administration in young adult male Avy/a mice. It appears the Avy/a
      locomotor and thigmotaxic responses to acute nicotine administration are not
      mediated solely by hypothalamic-pituitary-adrenal (HPA) axis stimulation.

PMID- 24289263
TI  - Brain white matter microstructure alterations in adolescent rhesus monkeys
      exposed to early life stress: associations with high cortisol during infancy.
AB  - BACKGROUND: Early adverse experiences, especially those involving disruption of
      the mother-infant relationship, are detrimental for proper socioemotional
      development in primates. Humans with histories of childhood maltreatment are at
      high risk for developing psychopathologies including depression, anxiety,
      substance abuse, and behavioral disorders. However, the underlying
      neurodevelopmental alterations are not well understood. Here we used a nonhuman
      primate animal model of infant maltreatment to study the long-term effects of
      this early life stress on brain white matter integrity during adolescence, its
      behavioral correlates, and the relationship with early levels of stress hormones.
      METHODS: Diffusion tensor imaging and tract based spatial statistics were used to
      investigate white matter integrity in 9 maltreated and 10 control animals during
      adolescence. Basal plasma cortisol levels collected at one month of age (when
      abuse rates were highest) were correlated with white matter integrity in regions
      with group differences. Total aggression was also measured and correlated with
      white matter integrity. RESULTS: We found significant reductions in white matter
      structural integrity (measured as fractional anisotropy) in the corpus callosum,
      occipital white matter, external medullary lamina, as well as in the brainstem of
      adolescent rhesus monkeys that experienced maternal infant maltreatment. In most
      regions showing fractional anisotropy reductions, opposite effects were detected
      in radial diffusivity, without changes in axial diffusivity, suggesting that the
      alterations in tract integrity likely involve reduced myelin. Moreover, in most
      regions showing reduced white matter integrity, this was associated with elevated
      plasma cortisol levels early in life, which was significantly higher in
      maltreated than in control infants. Reduced fractional anisotropy in occipital
      white matter was also associated with increased social aggression. CONCLUSIONS:
      These findings highlight the long-term impact of infant maltreatment on brain
      white matter structural integrity, particularly in tracts involved in visual
      processing, emotional regulation, and somatosensory and motor integration. They
      also suggest a relationship between elevations in stress hormones detected in
      maltreated animals during infancy and long-term brain white matter structural
      effects.

PMID- 24289266
TI  - Usage patterns and adverse experiences in traditional Korean medicine: results of
      a survey in South Korea.
AB  - BACKGROUND: Although traditional medicine (TM) in South Korea is included in the
      national health care system, it is considered complementary and alternative
      medicine (CAM), and not mainstream medicine. Therefore, the lack of statistical
      data regarding the usage and adverse experiences of traditional Korean medicine
      (TKM) makes difficult to understand the current status of TM. In this study, we
      aimed to report usage patterns and adverse experiences on TKM targeting consumers
      in South Korea. METHODS: A total of 2000 consumers participated in the survey on
      usage and adverse experiences in 2008. Among the 2,000 participants, 915 (45.8%)
      had taken herbal medicine or received traditional medicinal therapies; these
      individuals were further surveyed on the internet or in an interview. RESULTS:
      The usage rate was higher among women and among patients in their 30s. Of the
      total TKM usage, acupuncture accounted for 36.7%, and herbal medicine accounted
      for 13.4%. Regarding the frequency of use of TKM, 73.8% of patients reported
      using TM less than 5 times in 1 year. Of the 915 respondents, 8.2% of individuals
      had some type of adverse experience resulting from TKM. Adverse experiences were
      primarily caused by acupuncture and herbal medicines, and they primarily involved
      diseases of the digestive system and skin. The incidence of adverse experiences
      was less than 3.7% for acupuncture and 3.8% for herbal medicine. Overall, the
      incidence rate of adverse experiences for TKM for the entire population was 0.04
      per 10,000 individuals. CONCLUSIONS: The medical usage and occurrence of adverse
      events on TKM should be surveyed periodically, and the statistical trends should
      be analysed. The disparity between the survey results for traditional herbal
      medicines and medical practices, and those for the national pharmacovigilance
      system or academic reports of adverse experiences should be examined. The
      national pharmacovigilance system must be improved to compensate for the
      disparities. Policies and regulations are required to enhance the reporting of
      adverse experiences not only for herbal medicines but also for traditional
      medicinal therapies.

PMID- 24289265
TI  - Construction of high-density genetic linkage maps for orange-spotted grouper
      Epinephelus coioides using multiplexed shotgun genotyping.
AB  - BACKGROUND: Orange-spotted grouper, Epinephelus coioides, is one of the most
      valuable fish species in China. Commercial production of orange-spotted grouper
      could be increased by developing higher growth rates and improving commercially
      important traits. Information on genetic markers associated with quantitative
      trait loci (QTL) can be used in breeding programs to identify and select
      individuals carrying desired traits. A high-density genetic linkage map is the
      basis for QTL study, and multiplexed shotgun genotyping (MSG) facilitates the
      development of single nucleotide polymorphisms (SNPs) and genotyping. In this
      study, the first high-density genetic linkage maps for groupers were generated on
      the basis of the MSG method. RESULTS: The sex-averaged map contained a total of
      4,608 SNPs, which spanned 1581.7 cM, with a mean distance between SNPs of 0.34
      cM. The 4,608 SNPs were located in 2,849 unique locations on the linkage map,
      with an average inter-location space at 0.56 cM. There were 2,516 SNPs on the
      female map, and the number of unique locus was 1,902. However, the male map
      contained more numbers of SNP (2,939) and unique locations (2,005). The total
      length of the female and male maps was 1,370.9 and 1,335.5 cM, respectively.
      CONCLUSIONS: The high-resolution genetic linkage maps will be very useful for QTL
      analyses and marker-assisted selection (MAS) for economically important traits in
      molecular breeding of the orange-spotted grouper.

PMID- 24289267
TI  - Egg yolk: an unusual trigger of food protein-induced enterocolitis syndrome.

PMID- 24289268
TI  - Long-lasting response to electrochemotherapy in melanoma patients with cutaneous
      metastasis.
AB  - BACKGROUND: Treatment of early and multiple cutaneous unresectable recurrences is
      a major therapeutic problem with around 80% of patients relapsing within 5 years.
      For lesions refractory to elective treatments, electrochemotherapy (ECT)
      involving electroporation combined with antineoplastic drug treatment appears to
      be a new potential option. This study was undertaken to analyze the short- and
      long-term responses of lesions treated with ECT with intravenous injection of
      bleomycin in melanoma patients with in-transit disease or distant cutaneous
      metastases. METHODS: Between June 2007 and September 2012, 60 patients with
      relapsed and refractory cutaneous melanoma metastases or in-transit disease
      underwent 100 courses of ECT with intravenous injection of bleomycin. Response to
      treatment was evaluated three months after ECT. A long-lasting response was
      defined as no cutaneous or in-transit relapse after a minimum of six months.
      RESULTS: Three months after ECT, a complete response was observed in 29 patients
      (48.4%), a partial response in 23 patients (38.3%) and no change or progressive
      disease in 8 patients (13.3%). The objective response rate of all treated lesions
      was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long
      lasting response after one ECT session and were disease-free after a mean
      duration of follow-up of 27.5 months. CONCLUSIONS: The favorable outcome obtained
      in the present study demonstrates that ECT is a reliable, and effective procedure
      that provides long-term benefit in terms of curative and palliative treatment for
      unresectable cutaneous lesions without adversely impacting the quality of life of
      patients.

PMID- 24289269
TI  - Parvovirus B19 at the culprit coronary stenosis predicts outcome after stenting.
AB  - BACKGROUND: Parvovirus (PV) B19 DNA is detected in endothelial cells and may
      cause endothelial dysfunction, which is involved in in-stent restenosis. We aimed
      at performing an exploratory analysis that evaluated if PVB19 DNA at the culprit
      coronary stenosis would be associated with an increased rate of major adverse
      cardiac events (MACE) after coronary stenting. MATERIALS AND METHODS: Consecutive
      patients undergoing stent implantation for stable or unstable coronary artery
      disease were enroled. Serology for PVB19 infection and presence of DNA for PVB19
      on balloons used for predilatation were assessed in all patients. MACE rate, as a
      composite of cardiac death, myocardial infarction (MI) or clinically driven
      target lesion revascularization (TLR) was obtained at 24 month follow-up.
      Adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for
      variables associated with MACE. RESULTS: One hundred and nine patients [age 66 +/
      10, male sex 89 (82%)] were enroled. At 24-month follow-up, 18 patients
      experienced a MACE. Two patients (2%) experienced MI, while 16 patients (15%)
      experienced clinically driven TLR. At multiple Cox regression analysis, the
      presence of PVB19 DNA on the balloon and the use of bare-metal stents were
      independent predictors of MACE [HR 3.30, 95% CI (1.12-10.08), P = 0.03 and HR
      4.19, 95% CI (1.60-10.94), P = 0.003]. CONCLUSIONS: PVB19 DNA detected on the
      balloon used for dilatation of coronary stenosis before stent implantation is
      associated with MACE rate at follow-up, mainly due to clinically driven TLR. The
      results of this exploratory analysis should be confirmed in a larger population.

PMID- 24289270
TI  - Natalizumab for multiple sclerosis: appraising risk versus benefit, a seemingly
      demanding tango.
AB  - INTRODUCTION: Natalizumab is a highly effective monoclonal antibody used for the
      treatment of multiple sclerosis (MS). It reduces relapses, delays the onset of
      disease progression and improves disease outcomes in relapsing-remitting MS.
      However, treatment with natalizumab is associated with progressive multifocal
      leukoencephalopathy (PML), a severe opportunistic brain infection with John
      Cunningham virus. AREAS COVERED: In this review, we discuss the mechanism of
      action, results of pivotal studies, clinical use and adverse effects associated
      with natalizumab therapy with emphasis on PML. A risk stratification strategy to
      optimize natalizumab therapy is included. This review also summarizes the
      alternative and upcoming therapies available for the treatment of MS. EXPERT
      OPINION: Natalizumab is a very effective therapy for MS and has shown tremendous
      results in reducing the disease activity and improving patients' quality of life.
      Serious adverse effect such as PML warrant extreme caution and heightened
      clinical vigilance while prescribing the drug. If used with prudence, the drug
      can be instrumental in treatment of patients with inadequate response to the
      first-line medications.

PMID- 24289272
TI  - Propranolol for the treatment of infantile haemangiomas: our experience with 44
      patients.
AB  - Propranolol is an effective, safe treatment for complicated infantile
      haemangiomas (IH). We evaluated all patients (n = 44) with IH treated with
      propranolol in our department. Of the 44 patients who were begun on propranolol
      therapy, 26 patients have completed the treatment to date and all had a good
      response. The mean duration of treatment was 45.7 weeks. Four patients developed
      rebound growth of their IH, which responded to the reintroduction of propranolol.
      Two patients with PHACES (posterior fossa malformations, haemangiomas, arterial
      anomalies, coarctation of the aorta/cardiac abnormalities, eye anomalies and
      sternal defects/supraumbilical raphe) syndrome were treated with lower than
      standard doses, because of concern about possible cerebrovascular compromise.
      Adverse effects were minor in most patients. Three patients discontinued
      propranolol because of vomiting, wheeze, and hypoglycaemia, respectively. Our
      duration of treatment was longer than that of other series, and may be due to our
      group having higher rates of hypotension, recorded in 27.3% of patients,
      precluding an increase in propranolol dose. Our experience supports that
      propranolol is an effective first-line agent for complicated IH.

PMID- 24289271
TI  - A systematic review of heterosexual anal intercourse and its role in the
      transmission of HIV and other sexually transmitted infections in Papua New
      Guinea.
AB  - BACKGROUND: Papua New Guinea (PNG) has a high burden of sexually transmitted
      infections (STIs) and the highest adult HIV prevalence in the Pacific region.
      Despite this burden of disease, heterosexual anal intercourse (HAI) has rarely
      been considered. Given the increasing number of, and interest in, behavioural
      surveys in PNG and the changing nature of PNG's HIV epidemic, it is timely to
      conduct a systematic review of HAI in PNG order to improve sexual health.
      METHODS: We performed a systematic review of HAI in PNG as reported in peer
      reviewed and non-peer-reviewed publications for the period 1950-May 2012. The
      search strategy identified 475 publications. After screening by geographical
      location, topic and methodology, we identified 23 publications for full text
      review, following which 13 publications were included in the final review. Using
      data from the review, we performed a risk equation analysis to demonstrate the
      potential impact of HAI on HIV acquisition and incidence in PNG. RESULTS: There
      is a paucity of well-informed behavioural research on HAI in PNG. Inconsistency
      in key questions on HAI made it impossible to conduct a meta-analysis. The data
      available on HAI shows that it is practiced in all geographical areas and among
      all populations. Of those who reported HAI, rates varied from as low as 8% to as
      high as 77% depending on the recall period and partner type. Condom use during
      HAI was consistently low. Our risk equation analysis indicates that even if only
      20% of females engage in HAI, and only 10% of sex acts involve HAI, the total
      number of new HIV infections among females would be 40% greater than if vaginal
      intercourse only occurred. CONCLUSIONS: Our findings of indicate that HAI may be
      an important driver of the HIV epidemic in PNG. In order to improve the sexual
      health of Papua New Guineans, efforts are required to improve behavioural
      surveillance of HAI as well as develop national HIV/STI programing and policy to
      better address the risks associated with unprotected HAI.

PMID- 24289273
TI  - Gene-environment interaction effects on lung function- a genome-wide association
      study within the Framingham heart study.
AB  - BACKGROUND: Previous studies in occupational exposure and lung function have
      focused only on the main effect of occupational exposure or genetics on lung
      function. Some disease-susceptible genes may be missed due to their low marginal
      effects, despite potential involvement in the disease process through
      interactions with the environment. Through comprehensive genome-wide gene
      environment interaction studies, we can uncover these susceptibility genes. Our
      objective in this study was to explore gene by occupational exposure interaction
      effects on lung function using both the individual SNPs approach and the genetic
      network approach. METHODS: The study population comprised the Offspring Cohort
      and the Third Generation from the Framingham Heart Study. We used forced
      expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity
      (FVC) as outcomes. Occupational exposures were classified using a population
      specific job exposure matrix. We performed genome-wide gene-environment
      interaction analysis, using the Affymetrix 550 K mapping array for genotyping. A
      linear regression-based generalized estimating equation was applied to account
      for within-family relatedness. Network analysis was conducted using results from
      single-nucleotide polymorphism (SNP)-level analyses and from gene expression
      study results. RESULTS: There were 4,785 participants in total. SNP-level
      analysis and network analysis identified SNP rs9931086 (P(interaction) =1.16 *
      10(-7)) in gene SLC38A8, which may significantly modify the effects of
      occupational exposure on FEV1. Genes identified from the network analysis
      included CTLA-4, HDAC, and PPAR-alpha. CONCLUSIONS: Our study implies that SNP
      rs9931086 in SLC38A8 and genes CTLA-4, HDAC, and PPAR-alpha, which are related to
      inflammatory processes, may modify the effect of occupational exposure on lung
      function.

PMID- 24289274
TI  - SCISSORS: practical considerations.
AB  - Molecular similarity has been effectively applied to many problems in
      cheminformatics and computational drug discovery, but modern methods can be
      prohibitively expensive for large-scale applications. The SCISSORS method rapidly
      approximates measures of pairwise molecular similarity such as ROCS and LINGO
      Tanimotos, acting as a filter to quickly reduce the size of a problem. We report
      an in-depth analysis of SCISSORS performance, including a mapping of the SCISSORS
      error distribution, benchmarking, and investigation of several algorithmic
      modifications. We show that SCISSORS can accurately predict multiconformer
      similarity and suggest a method for estimating optimal SCISSORS parameters in a
      data set-specific manner. These results are a useful resource for researchers
      seeking to incorporate SCISSORS into molecular similarity applications. 

PMID- 24289275
TI  - Versatile pattern generation of periodic, high aspect ratio Si nanostructure
      arrays with sub-50-nm resolution on a wafer scale.
AB  - We report on a method of fabricating variable patterns of periodic, high aspect
      ratio silicon nanostructures with sub-50-nm resolution on a wafer scale. The
      approach marries step-and-repeat nanoimprint lithography (NIL) and metal
      catalyzed electroless etching (MCEE), enabling near perfectly ordered Si
      nanostructure arrays of user-defined patterns to be controllably and rapidly
      generated on a wafer scale. Periodic features possessing circular, hexagonal, and
      rectangular cross-sections with lateral dimensions down to sub-50 nm, in
      hexagonal or square array configurations and high array packing densities up to
      5.13 * 107 structures/mm2 not achievable by conventional UV photolithography are
      fabricated using this top-down approach. By suitably tuning the duration of
      catalytic etching, variable aspect ratio Si nanostructures can be formed. As the
      etched Si pattern depends largely on the NIL mould which is patterned by electron
      beam lithography (EBL), the technique can be used to form patterns not possible
      with self-assembly methods, nanosphere, and interference lithography for
      replication on a wafer scale. Good chemical resistance of the nanoimprinted mask
      and adhesion to the Si substrate facilitate good pattern transfer and preserve
      the smooth top surface morphology of the Si nanostructures as shown in TEM. This
      approach is suitable for generating Si nanostructures of controlled dimensions
      and patterns, with high aspect ratio on a wafer level suitable for semiconductor
      device production. 

PMID- 24289276
TI  - CO2 absorption and sequestration as various polymorphs of CaCO3 using sterically
      hindered amine.
AB  - One aspect of the attempt to restrain global warming is the reduction of the
      levels of atmospheric CO2 produced by fossil fuel power systems. This study
      attempted to develop a method that reduces CO2 emissions by investigating the
      absorption of CO2 into sterically hindered amine 2-amino-2-methyl-1-propanol
      (AMP), the acceleration of the absorption rate by using the enzyme carbonic
      anhydrase (CA), and the conversion of the absorption product to stable
      carbonates. CO2 absorbed by AMP is converted via a zwitterion mechanism to
      bicarbonate species; the presence of these anions was confirmed with (1)H and
      (13)C NMR spectral analysis. The catalytic efficiency (kcat/Km), CO2 absorption
      capacities, and enthalpy changes (DeltaHabs) of aqueous AMP in the presence or
      absence of CA were found to be 2.61 * 10(6) or 1.35 * 10(2) M(-1) s(-1), 0.97 or
      0.96 mol/mol, and -69 or -67 kJ/mol, respectively. The carbonation of AMP
      absorbed CO2 was performed by using various Ca(2+) sources, viz., CaCl2 (CAC),
      Ca(OOCCH3)2 (CAA), and Ca(OOCCH2CH3)2 (CAP), to obtain various polymorphs of
      CaCO3. The yields of CaCO3 from the Ca(2+) sources were found in the order CAP >
      CAA > CAC as a result of the effects of the corresponding anions. CAC produces
      pure rhombohedral calcite, and CAA and CAP produce the unusual phase
      transformation of calcite to spherical vaterite crystals. Thus, AMP in
      combination with CAA and CAP can be used as a CO2 absorbent and buffering agent
      for the sequestration of CO2 in porous CaCO3. 

PMID- 24289277
TI  - Quantitative summaries of treatment effect estimates obtained with network meta
      analysis of survival curves to inform decision-making.
AB  - BACKGROUND: Increasingly, network meta-analysis (NMA) of published survival data
      are based on parametric survival curves as opposed to reported hazard ratios to
      avoid relying on the proportional hazards assumption. If a Bayesian framework is
      used for the NMA, rank probabilities associated with the alternative treatments
      can be obtained, which directly support decision-making. In the context of
      survival analysis multiple treatment effect measures are available to inform the
      rank probabilities. METHODS: A fractional polynomial NMA of overall survival in
      advanced melanoma was performed as an illustrative example. Rank probabilities
      were calculated and presented for the following effect measures: 1) median
      survival; 2) expected survival; 3) mean survival at the follow-up time point of
      the trial with the shortest follow-up; 4) hazard or hazard ratio over time; 5)
      cumulative hazard or survival proportions over time; and 6) mean survival at
      subsequent time points. The advantages and disadvantages of the alternative
      measures were discussed. RESULTS: Since hazard and survival estimates may vary
      over time for the compared interventions, calculations of rank probabilities for
      an NMA of survival curves may depend on the effect measure. With methods 1-3 rank
      probabilities do not vary over time, which are easier to understand and
      communicate than rank probabilities that vary over time as obtained with methods
      4-6. However, rank probabilities based on methods 4-6 provide useful information
      regarding the relative treatment effects over time. CONCLUSIONS: Different
      approaches to summarize results of a NMA of survival curves with rank
      probabilities have pros and cons. Rank probabilities of treatment effects over
      time provide a more transparent and informative approach to help guide decision
      making than single rank probabilities based on collapsed measures, such as median
      survival or expected survival. Rank probabilities based on survival proportions
      are the most intuitive and straightforward to communicate, but alternatives based
      on the hazard function or mean survival over time may also be useful.

PMID- 24289278
TI  - Early handling attenuates enhancement of glucocorticoid receptors in the
      prefrontal cortex in an animal model of post-traumatic stress disorder.
AB  - BACKGROUND: Changes in glucocorticoid receptors (GRs) have been implicated in the
      pathogenesis of stress related psychiatric disorders such as depression and post
      traumatic stress disorder (PTSD). Abnormal adaptation of the stress-response
      system following traumatic stress can lead to an altered hypothalamic-pituitary
      adrenal axis that may contribute to PTSD development. Indeed, elevated GR
      expression in the hippocampus and prefrontal cortex linked to PTSD-like
      characteristics have been reported in the validated animal model of PTSD, single
      prolonged stress. These findings implicate increased levels of GRs in the
      development of post-traumatic psychopathology and suggest that exploration of GR
      targeted interventions may have potential for PTSD prevention. Early handling
      during the neonatal phase alters GR expression and is proposed to confer
      resilience to stress. We therefore examined the effects of combined early
      handling and single prolonged stress treatments on GR expression. METHODS: Timed
      pregnant dams gave birth to pups that were subjected to early handling (n = 11)
      or control (n = 13) procedures during the neonatal phase. At postnatal day 45
      animals underwent single prolonged stress or a control procedure. Rats were
      euthanized one day later and GR levels were assayed using western blot
      electrophoresis. RESULTS: Single prolonged stress exposure enhanced GR expression
      in the hippocampus and prefrontal cortex. Early handling treatment protected
      against single prolonged stress-induced enhancement of GR expression in the
      prefrontal cortex, but not in the hippocampus. CONCLUSIONS: These data are a
      first step in highlighting the importance of targeting GR systems in
      prevention/resilience and may suggest that preventive strategies targeting GR
      upregulation might be particularly effective when prefrontal rather than
      hippocampal GRs are the target.

PMID- 24289279
TI  - Radioactive iodine treatment for node negative papillary thyroid cancer with
      capsular invasion only: Results of a large retrospective study.
AB  - AIM: With thyroid carcinoma the decision to use radioactive iodine (RAI) ablation
      depends on the risk of poor outcomes. Although extrathyroid extension (ETE) is
      well known as a risk of poor outcomes for papillary thyroid carcinoma (PTC), the
      definition of minimal ETE is too broad, as it encompasses both microscopic
      invasion of the thyroid capsule (capsular invasion [CI]) and macroscopic invasion
      of the sternothyroid muscle. METHODS: We conducted a retrospective study to
      analyze the prognostic benefit of RAI ablation according to the presence of CI in
      a consecutive series of patients with PTC between October 1997 and December 2008.
      We studied two groups of patients, including those who received RAI (group I, n =
      121) and those who did not (group II, n = 108). During follow-up, we assessed the
      locoregional recurrence of all patients. RESULTS: There were no statistically
      significant difference between the groups regarding locoregional recurrence at
      follow-up (13.2% for group I vs 9.3% for group II, P = 0.441). The association
      between RAI and locoregional recurrence in PTC patients with CI remained
      insignificant after adjusting for potential confounders, such as age, tumor size,
      sex, lymphatic invasion, vascular invasion and tumor multiplicity (P = 0.409,
      hazard ratio = 0.698, 95% confidence interval, 0.298-1.639). CONCLUSIONS: This
      retrospective study suggests that RAI treatment is not associated with less
      locoregional recurrence in PTC patients who only demonstrate CI, although further
      prospective studies are required to confirm these findings.

PMID- 24289280
TI  - A cross-sectional study of public attitudes towards safer drug use practices in
      British Columbia, Canada.
AB  - BACKGROUND: Harm reduction programs are often vulnerable to political and vocal
      opposition despite documented evidence of their effectiveness and economic
      benefit. It is not well understood if opponents to harm reduction represent the
      general public's attitudes. OBJECTIVE: To understand the attitudes of the people
      of British Columbia (BC) towards various harm reduction strategies and services,
      and factors associated with support for harm reduction. METHODS: A random-digit
      dialing telephone survey assessing attitudes towards various harm reduction
      strategies was administered to British Columbians in August 2011 (n = 2000). We
      compared the level of support for general harm reduction by sex, age, education
      level, and area of residence (Health Authority region) (chi2). Multivariate
      logistic regression was used to assess odds of support for harm reduction.
      RESULTS: Overall support for general harm reduction among participants was 76%;
      needle distribution 72%; needle distribution in one's local community 65%; and
      safer inhalation equipment distribution 52%. In the multivariate analysis, those
      with significantly lower odds of supporting harm reduction were male, older, had
      equal or less than high school education or completed a certificate/diploma
      program, and resided in the Fraser Health Authority region. The Health Authority
      region with a municipality that has introduced a bylaw prohibiting the
      implementation of harm reduction services was found to have 69% support for harm
      reduction. Another Health Authority region with a municipality that closed a long
      standing needle distribution site was found to have over 78% support. CONCLUSION:
      In contrast to some local policies, our results show the British Columbians
      surveyed in our study support harm reduction. It is unclear whether policy makers
      are swayed by a vocal minority or block harm reduction activities for other
      reasons. Tailoring messages towards segments of the public less likely to support
      harm reduction, as well civic policy-makers and the media, may help to reduce
      stigma and gain support for harm reduction services designed to protect and
      improve the health of the individual and the public.

PMID- 24289281
TI  - Effect of the Bologna bachelor degree on considerations of medical students to
      interrupt or terminate their medical training.
AB  - BACKGROUND: The bachelor-master system potentially enables medical students to
      stop or temporary interrupt their training after obtaining a bachelor degree. A
      survey at the time of introduction of this two-cycle model in Dutch medical
      education showed little interest among students in these possibilities. AIMS: To
      investigate students' considerations to stop or pause now that this model is well
      established. METHODS: Questionnaires were sent to 314 second year and 348 third
      year bachelor students and 256 first year master students at University Medical
      Center Utrecht. RESULTS: Response rates were 33.4% for the second year and 42.0%
      for the third year bachelor students and 48.8% for the master students. Of all
      these students, one to three percent seriously considered a permanent stop. Of
      the bachelor students, about one quarter seriously considered a temporary stop
      after finishing the bachelor program. Of the master students, one in seven
      indicated that they did take a break at that opportunity. CONCLUSIONS: Awarding
      the bachelor degree does not particularly encourage students to discontinue their
      medical study. Our results are comparable to the results of the survey at the
      time of the introduction of the bachelor-master system, which supports our
      previous conclusion.

PMID- 24289283
TI  - Hand-held health records for individuals with intellectual disability: a
      systematic review.
AB  - BACKGROUND: Hand-held health records (HHHRs) aim to empower individuals with
      intellectual disability (ID) and improve the communication between all those
      involved in their health care. HHHRs can be used to identify additional health
      needs and contribute to improved treatment for individuals with ID. This review
      summarises evidence concerning the use of HHHRs with individuals with ID.
      METHODS: Systematic searching of electronic databases and email contact with
      established researchers in the field were used to identify relevant articles
      related to the use of HHHRs among individuals with ID. RESULTS: Seven articles
      were identified and included for review. Studies involved the development,
      evaluation, acceptability and facilitators and barriers of implementation of
      HHHRs. HHHRs did not lead to improved short-term healthcare activity, but did
      lead to more discussion about health problems, increased health-related knowledge
      and awareness of personal health issues. CONCLUSIONS: HHHRs are well accepted
      among users with ID. However, no short-term benefits were found and future
      research needs to examine the long-term effects of HHHRs.

PMID- 24289284
TI  - Advice provided by health professionals regarding precautionary allergen
      labelling.

PMID- 24289282
TI  - Positron emission tomography of the vulnerable atherosclerotic plaque in man--a
      contemporary review.
AB  - Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD).
      It is the leading cause of morbidity and mortality in the Western world today and
      is set to become the prevailing disease and major cause of death worldwide by
      2020. In the 1950s surgical intervention was introduced to treat symptomatic
      patients with high-grade carotid artery stenosis due to atherosclerosis--a
      procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic
      plaque from the affected carotid artery of these patients, CEA is beneficial by
      preventing subsequent ipsilateral ischemic stroke. However, it is known that
      patients with low to intermediate artery stenosis may still experience ischemic
      events, leading clinicians to consider plaque composition as an important feature
      of atherosclerosis. Today molecular imaging can be used for characterization,
      visualization and quantification of cellular and subcellular physiological
      processes as they take place in vivo; using this technology we can obtain
      valuable information on atherosclerostic plaque composition. Applying molecular
      imaging clinically to atherosclerotic disease therefore has the potential to
      identify atherosclerotic plaques vulnerable to rupture. This could prove to be an
      important tool for the selection of patients for CEA surgery in a health system
      increasingly focused on individualized treatment. This review focuses on current
      advances and future developments of in vivo atherosclerosis PET imaging in man.

PMID- 24289285
TI  - Pneumocystis pneumonia induced by treatment with low-dose tacrolimus and
      methylprednisolone in a patient with rheumatoid arthritis: a case report.
AB  - BACKGROUND: Tacrolimus is an immunosuppressive drug used to prevent acute
      rejection following organ transplantation and to treat autoimmune disease.
      Tacrolimus is usually prescribed in such situation at a dose of 3.0 mg/day.
      Pneumocystis pneumonia induced by this dose of tacrolimus has been reported in
      many cases; however, we encountered a rare case of Pneumocystis pneumonia induced
      by low-dose tacrolimus and methylprednisolone. CASE PRESENTATION: We herein
      report the case of an 82-year-old Asian Japanese female with rheumatoid arthritis
      and Pneumocystis pneumonia who was being treated with low-dose tacrolimus and low
      dose methylprednisolone therapy. She was diagnosed with rheumatoid arthritis at
      52 years of age and was administered oral low-dose methylprednisolone and
      salazosulfapyridine. Her condition had been stable under this treatment for 30
      years. However, her arthralgia worsened three months before admission. The
      salazosulfapyridine was changed to tacrolimus (0.5 mg/day) by her physician, and
      her arthralgia almost completely disappeared. She was admitted to our hospital
      for Pseudomonas pneumonia, and her symptoms improved almost completely with
      intravenous ceftazidime therapy. However, on the 14th day of admission, she
      developed acute respiratory failure due to Pneumocystis pneumonia and died on the
      17th day of admission in spite of adequate treatment. CONCLUSION: Our report
      highlights the importance of providing prompt prevention, diagnosis and treatment
      of Pneumocystis pneumonia in rheumatoid arthritis patients under tacrolimus and
      low-dose methylprednisolone therapy.

PMID- 24289288
TI  - Linking manipulative experiments to field data to test the dilution effect.
AB  - The dilution effect, the hypothesis that biodiversity reduces disease risk, has
      received support in many systems. However, few dilution effect studies have
      linked mechanistic experiments to field patterns to establish both causality and
      ecological relevance. We conducted a series of laboratory experiments and tested
      the dilution effect hypothesis in an amphibian-Batrachochytrium dendrobatidis
      (Bd) system and tested for consistency between our laboratory experiments and
      field patterns of amphibian species richness, host identity and Bd prevalence. In
      our laboratory experiments, we show that tadpoles can filter feed Bd zoospores
      and that the degree of suspension feeding was positively associated with their
      dilution potential. The obligate suspension feeder, Gastrophryne carolinensis,
      generally diluted the risk of chytridiomycosis for tadpoles of Bufo terrestris
      and Hyla cinerea, whereas tadpoles of B. terrestris (an obligate benthos feeder)
      generally amplified infections for the other species. In addition, G.
      carolinensis reduced Bd abundance on H. cinerea more so in the presence than
      absence of B. terrestris and B. terrestris amplified Bd abundance on H. cinerea
      more so in the absence than presence of G. carolinensis. Also, when ignoring
      species identity, species richness was a significant negative predictor of Bd
      abundance. In our analysis of field data, the presence of Bufo spp. and
      Gastrophryne spp. were significant positive and negative predictors of Bd
      prevalence, respectively, even after controlling for climate, vegetation,
      anthropogenic factors (human footprint), species richness and sampling effort.
      These patterns of dilution and amplification supported our laboratory findings,
      demonstrating that the results are likely ecologically relevant. The results from
      our laboratory and field data support the dilution effect hypothesis and also
      suggest that dilution and amplification are predictable based on host traits. Our
      study is among the first to link manipulative experiments, in which a potential
      dilution mechanism is supported, with analyses of field data on species richness,
      host identity, spatial autocorrelation and disease prevalence.

PMID- 24289286
TI  - Transcriptome and proteome quantification of a tumor model provides novel
      insights into post-transcriptional gene regulation.
AB  - BACKGROUND: Genome-wide transcriptome analyses have given systems-level insights
      into gene regulatory networks. Due to the limited depth of quantitative
      proteomics, however, our understanding of post-transcriptional gene regulation
      and its effects on protein-complex stoichiometry are lagging behind. RESULTS:
      Here, we employ deep sequencing and the isobaric tag for relative and absolute
      quantification (iTRAQ) technology to determine transcript and protein expression
      changes of a Drosophila brain tumor model at near genome-wide resolution. In
      total, we quantify more than 6,200 tissue-specific proteins, corresponding to
      about 70% of all transcribed protein-coding genes. Using our integrated data set,
      we demonstrate that post-transcriptional gene regulation varies considerably with
      biological function and is surprisingly high for genes regulating transcription.
      We combine our quantitative data with protein-protein interaction data and show
      that post-transcriptional mechanisms significantly enhance co-regulation of
      protein-complex subunits beyond transcriptional co-regulation. Interestingly, our
      results suggest that only about 11% of the annotated Drosophila protein complexes
      are co-regulated in the brain. Finally, we refine the composition of some of
      these core protein complexes by analyzing the co-regulation of potential
      subunits. CONCLUSIONS: Our comprehensive transcriptome and proteome data provide
      a valuable resource for quantitative biology and offer novel insights into
      understanding post-transcriptional gene regulation in a tumor model.

PMID- 24289287
TI  - Genome-wide analysis of coordinated transcript abundance during seed development
      in different Brassica rapa morphotypes.
AB  - BACKGROUND: Brassica seeds are important as basic units of plant growth and
      sources of vegetable oil. Seed development is regulated by many dynamic metabolic
      processes controlled by complex networks of spatially and temporally expressed
      genes. We conducted a global microarray gene co-expression analysis by measuring
      transcript abundance of developing seeds from two diverse B. rapa morphotypes: a
      pak choi (leafy-type) and a yellow sarson (oil-type), and two of their doubled
      haploid (DH) progenies, (1) to study the timing of metabolic processes in
      developing seeds, (2) to explore the major transcriptional differences in
      developing seeds of the two morphotypes, and (3) to identify the optimum stage
      for a genetical genomics study in B. rapa seed. RESULTS: Seed developmental
      stages were similar in developing seeds of pak choi and yellow sarson of B. rapa;
      however, the colour of embryo and seed coat differed among these two morphotypes.
      In this study, most transcriptional changes occurred between 25 and 35 DAP, which
      shows that the timing of seed developmental processes in B. rapa is at later
      developmental stages than in the related species B. napus. Using a Weighted Gene
      Co-expression Network Analysis (WGCNA), we identified 47 "gene modules", of which
      27 showed a significant association with temporal and/or genotypic variation. An
      additional hierarchical cluster analysis identified broad spectra of gene
      expression patterns during seed development. The predominant variation in gene
      expression was according to developmental stages rather than morphotype
      differences. Since lipids are the major storage compounds of Brassica seeds, we
      investigated in more detail the regulation of lipid metabolism. Four co-regulated
      gene clusters were identified with 17 putative cis-regulatory elements predicted
      in their 1000 bp upstream region, either specific or common to different lipid
      metabolic pathways. CONCLUSIONS: This is the first study of genome-wide profiling
      of transcript abundance during seed development in B. rapa. The identification of
      key physiological events, major expression patterns, and putative cis-regulatory
      elements provides useful information to construct gene regulatory networks in B.
      rapa developing seeds and provides a starting point for a genetical genomics
      study of seed quality traits.

PMID- 24289289
TI  - Shear flow controlled morphological polydispersity of amphiphilic ABA triblock
      copolymer vesicles.
AB  - Self-assembled polymeric aggregates are generally polydisperse in morphology due
      to the existence of many metastable states in the system. This shortcoming
      becomes a bottleneck for preparing high quality self-assembled polymeric
      materials. An important concern is the possibility of controlling morphological
      polydispersity through the modulation of the metastable states. In this study,
      both simulative and experimental results show that the metastable states can be
      modulated. As a typical example, the morphological polydispersity of amphiphilic
      ABA triblock copolymer vesicles have been successfully controlled by shear flow.
      A higher shear rate results in more uniform and smaller vesicles. However, if the
      shear rate is extremely high, small spheres and short rods can be observed. These
      findings not only give a deeper insight into the metastable behavior of self
      assembled polymeric aggregates but also provide a new strategy for improving the
      uniformity of vesicles. 

PMID- 24289291
TI  - Ranking COMMPS chemical substances by an improved POT/RLE approach.
AB  - The combined monitoring-based and modeling-based priority setting (COMMPS)
      provides a procedure for the identification of priority hazardous substances
      outlined in the Working Document (ENV/191000/01 of January 16, 2001). This
      procedure is based on scoring a set of criteria which individually make
      substances more or less hazardous. The way scores are weighted and combined has
      been established by a panel of experts. Different authors outlined how such a
      procedure might be affected by subjectiveness of judgment, and alternative
      solutions based on partial order theory (POT) and random linear extensions (RLE)
      have been suggested. This method consists of generating a set of RLE and of
      averaging the rank given to each substance, so that a total order could be
      determined. Any POT/RLE approach must face the issue of covering as much as
      possible the space of linear extensions that, in the case of the 85 substances
      considered by COMMPS, becomes extremely large, and an exhaustive generation of
      linear extension is not feasible. Therefore, having a faster algorithm would help
      to consider a larger number of linear extensions in a given time frame. In this
      paper, we discuss this problem, and we outline a possible solution. 

PMID- 24289290
TI  - Profiling of phenolic compounds and their antioxidant and anticancer activities
      in pandan (Pandanus amaryllifolius Roxb.) extracts from different locations of
      Malaysia.
AB  - BACKGROUND: Phytochemicals and antioxidants from plant sources are of increasing
      interest to consumers because of their roles in the maintenance of human health.
      Most of the secondary metabolites of herbs are used in a number of pharmaceutical
      products. METHODS: Secondary metabolites composition and content of five
      flavonoids and three phenolic acids were evaluated and determined in Pandanus
      amaryllifolius extracts from three different locations of Malaysia by RP-HPLC;
      Total phenolic and total flavonoid content were determined using Folin-Ciocalteau
      and aluminum chloride colorimetric assay; The antioxidant activity of the
      extracts was determined by the ferric reducing antioxidant potential (FRAP) assay
      and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. MTT (3-(4,5-Dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) Assay was employed to screen anticancer
      activity of extracts against MCF-7 cancer cell line. RESULTS: Highest value of
      total flavonoids (TF) and total phenolics (TP) was observed in pandan extract
      from Bachok locattion (1.87 mg/g DW and 6.72 mg/g DW) followed by Klang (1.32
      mg/g DW; 5.07 mg/g DW) and Pontian (1.12 mg/g DW; 4.88 mg/g DW). Rutin just
      detected from Bachok location with value of 0.082 mg/g DW. High content of
      epicatechin (0.035 mg/g DW) and naringin (0.325 mg/g DW) were observed from
      Bachok location while, highest content of catechin (0.613 mg/g DW) and kaempferol
      (0.278 mg/g DW) was observed in pandan extract from Klang location. The extract
      of pandan from Bachok exhibited highest value of gallic acid (0.423 mg/g DW) and
      cinnamic acid (0.084 mg/g DW). Ferrulic acid just detected from pandan extract of
      Bachok location with concentration of 0.281 mg/g DW. Between studied locations
      Bachok exhibited highest value of DPPH (64.27%) and FRAP (517.2 MUm of Fe (II)/g)
      activity followed by Klang (52.16%; 448.6 MUm of Fe (II)/g) and Pontian (50.10%;
      314.8 MUm of Fe (II)/g). The preliminary screening showed pandan extracts from 3
      locations possessed anticancer promoting activity against MCF-7 cell line, with
      78.3%, 70.5% and 67.4% inhibition rate, respectively. Maximum MCF-7cell line
      inhibition was observed in pandan extract from Bachok location. CONCLUSIONS: The
      samples collected from the North (Bachok) exhibited the highest TP, TF
      antioxidant and anticancer activity while those from the Southern portion
      (Pontian) appeared to have the lowest content of TP, TF and antioxidant activity.

PMID- 24289292
TI  - A novel splice-site mutation in the AAGAB gene segregates with hereditary
      punctate palmoplantar keratoderma and congenital dysplasia of the hip in a large
      family.
AB  - BACKGROUND: Palmoplantar keratoderma punctata (PPKP) is a heterogeneous group of
      disorders characterized by hyperkeratotic papules occurring over the palms and
      soles during adolescence. PPKP type 1, also known as PPKP Buschke-Fischer-Brauer
      type, was recently found to result from mutations in the AAGAB gene, encoding the
      p34 protein. PPKP type 1 is usually not associated with extracutaneous features.
      AIM: To investigate a large family in which PPKP1 was present in association with
      congenital dysplasia of the hip (CDH). METHODS: A combination of direct
      sequencing of candidate genes and reverse-transcription PCR was used to identify
      the molecular basis underlying the clinical features displayed by the patients.
      RESULTS: Direct sequencing showed a novel intronic mutation in AAGAB, which was
      found to cosegregate with PPKP and CDH throughout the family. The mutation was
      found to result in aberrant RNA splicing, leading to exon 4 skipping.
      CONCLUSIONS: This observation suggests either the existence of a CDH-associated
      gene in the vicinity of AAGAB, or a hitherto unrecognized role for p34 during
      skeletal development.

PMID- 24289293
TI  - Current evaluation of alemtuzumab in multiple sclerosis.
AB  - INTRODUCTION: Alemtuzumab is a humanized IgG1 kappa monoclonal antibody approved
      for treatment of B-cell chronic lymphocytic leukemia. This cytolytic antibody is
      directed against CD52 and depletes lymphocytes, with monocytes, macrophages,
      natural killer cells and a subpopulation of granulocytes being affected to a much
      lesser degree. Alemtuzumab is currently under review to treat relapsing multiple
      sclerosis (MS) in the United States, based on positive Phase II and Phase III
      trials in both treatment-naive and treated relapsing MS patients. There was
      excellent efficacy in suppressing both clinical and neuroimaging disease
      activities. In these trials, the comparator arm was not placebo, but high dose
      frequently dosed subcutaneous interferon beta 1a. Alemtuzumab has recently been
      approved by the European authorities for active relapsing MS, in essence as a
      first-line agent. It produces long-standing effects, consistent with an induction
      agent. Efficacy will have to be weighed against risk of adverse effects, which
      include autoimmune disorders and infection. Alemtuzumab joins an increasingly
      crowded market, and will add to the complexity of treating MS. AREAS COVERED:
      This review will discuss alemtuzumab as a therapy for MS, reviewing PubMed for
      clinical trials, publications and presentations at international meetings. It
      will focus on a United States market perspective. EXPERT OPINION: Alemtuzumab
      offers induction strategy for very active relapsing MS patients who have failed
      conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab
      use is likely to be restricted to specialized MS centers, with long-term
      monitoring to determine the true risk for adverse effects.

PMID- 24289294
TI  - Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial
      cells exposed to airborne ZnO nanoparticles at the air-liquid interface.
AB  - Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach
      the alveolar region. Accumulating observations support a role for zinc oxide
      (ZnO) NP dissolution in toxicity, but the majority of in-vitro studies were
      conducted in cells exposed to NPs in growth media, where large doses of dissolved
      ions are shed into the exposure solution. To determine the precise intracellular
      accumulation dynamics and fate of zinc ions (Zn(2+)) shed by airborne NPs in the
      cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at
      the air-liquid interface (ALI). Using a fluorescent indicator for Zn(2+),
      together with organelle-specific fluorescent proteins, we quantified Zn(2+) in
      single cells and organelles over time. We found that at the ALI, intracellular
      Zn(2+) values peaked 3 h post exposure and decayed to normal values by 12 h,
      while in submerged cultures, intracellular Zn(2+) values continued to increase
      over time. The lowest toxic NP dose at the ALI generated peak intracellular
      Zn(2+) values that were nearly three-folds lower than the peak values generated
      by the lowest toxic dose of NPs in submerged cultures, and eight-folds lower than
      the peak values generated by the lowest toxic dose of ZnSO4 or Zn(2+). At the
      ALI, the majority of intracellular Zn(2+) was found in endosomes and lysosomes as
      early as 1 h post exposure. In contrast, the majority of intracellular Zn(2+)
      following exposures to ZnSO4 was found in other larger vesicles, with less than
      10% in endosomes and lysosomes. Together, our observations indicate that low but
      critical levels of intracellular Zn(2+) have to be reached, concentrated
      specifically in endosomes and lysosomes, for toxicity to occur, and point to the
      focal dissolution of the NPs in the cellular environment and the accumulation of
      the ions specifically in endosomes and lysosomes as the processes underlying the
      potent toxicity of airborne ZnO NPs. 

PMID- 24289295
TI  - Implementation strategies: recommendations for specifying and reporting.
AB  - Implementation strategies have unparalleled importance in implementation science,
      as they constitute the 'how to' component of changing healthcare practice. Yet,
      implementation researchers and other stakeholders are not able to fully utilize
      the findings of studies focusing on implementation strategies because they are
      often inconsistently labelled and poorly described, are rarely justified
      theoretically, lack operational definitions or manuals to guide their use, and
      are part of 'packaged' approaches whose specific elements are poorly understood.
      We address the challenges of specifying and reporting implementation strategies
      encountered by researchers who design, conduct, and report research on
      implementation strategies. Specifically, we propose guidelines for naming,
      defining, and operationalizing implementation strategies in terms of seven
      dimensions: actor, the action, action targets, temporality, dose, implementation
      outcomes addressed, and theoretical justification. Ultimately, implementation
      strategies cannot be used in practice or tested in research without a full
      description of their components and how they should be used. As with all
      intervention research, their descriptions must be precise enough to enable
      measurement and 'reproducibility.' We propose these recommendations to improve
      the reporting of implementation strategies in research studies and to stimulate
      further identification of elements pertinent to implementation strategies that
      should be included in reporting guidelines for implementation strategies. 

PMID- 24289296
TI  - Predictors of validity and reliability of a physical activity record in
      adolescents.
AB  - BACKGROUND: Poor to moderate validity of self-reported physical activity
      instruments is commonly observed in young people in low- and middle-income
      countries. However, the reasons for such low validity have not been examined in
      detail. We tested the validity of a self-administered daily physical activity
      record in adolescents and assessed if personal characteristics or the convenience
      level of reporting physical activity modified the validity estimates. METHODS:
      The study comprised a total of 302 adolescents from an urban and rural area in
      Ecuador. Validity was evaluated by comparing the record with accelerometer
      recordings for seven consecutive days. Test-retest reliability was examined by
      comparing registrations from two records administered three weeks apart. Time
      spent on sedentary (SED), low (LPA), moderate (MPA) and vigorous (VPA) intensity
      physical activity was estimated. Bland Altman plots were used to evaluate
      measurement agreement. We assessed if age, sex, urban or rural setting,
      anthropometry and convenience of completing the record explained differences in
      validity estimates using a linear mixed model. RESULTS: Although the record
      provided higher estimates for SED and VPA and lower estimates for LPA and MPA
      compared to the accelerometer, it showed an overall fair measurement agreement
      for validity. There was modest reliability for assessing physical activity in
      each intensity level. Validity was associated with adolescents' personal
      characteristics: sex (SED: P=0.007; LPA: P=0.001; VPA: P=0.009) and setting (LPA:
      P=0.000; MPA: P=0.047). Reliability was associated with the convenience of
      completing the physical activity record for LPA (low convenience: P=0.014; high
      convenience: P=0.045). CONCLUSIONS: The physical activity record provided
      acceptable estimates for reliability and validity on a group level. Sex and
      setting were associated with validity estimates, whereas convenience to fill out
      the record was associated with better reliability estimates for LPA. This
      tendency of improved reliability estimates for adolescents reporting higher
      convenience merits further consideration.

PMID- 24289297
TI  - Phytochemical, toxicological and antimicrobial evaluation of Lawsonia inermis
      extracts against clinical isolates of pathogenic bacteria.
AB  - BACKGROUND: The emerging resistance of pathogen against the currently available
      antimicrobial agents demands the search of new antimicrobial agents. The use of
      medicinal plants as natural substitute is the paramount area of research to
      overwhelm the drug resistance of infectious agents. Scientists have not made
      enough effort on the evaluation of safety of medicinal plant yet. METHODS: In the
      present study antimicrobial activity of Lawsonia inermis is investigated against
      clinical isolates of seven bacteria including four Gram negative (Escherichia
      coli, Salmonella typhi, Klebsiella spp., Shigella sonnei) and three Gram positive
      (Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis) using disc
      diffusion method. Four types of Lawsonia inermis extracts were prepared using
      methanol, chloroform, acetone and water as extraction solvents, while DMSO
      (Dimethyl sulfoxide) and water as dissolution solvents. The rate and extent of
      bacterial killing was estimated by time-kill kinetic assay at 1* MIC of each
      bacterial isolate. The overall safety of Lawsonia inermis extracts was assessed
      in mice. RESULTS: Lawsonia inermis displayed noteworthy antimicrobial activity
      against both gram positive and gram negative bacterial strains used in the study.
      The minimum value of MIC for different bacterial strains ranged from 2.31 mg/ml
      to 9.27 mg/ml. At 1x MIC of each bacterial isolate, 3log10 decrease in CFU was
      recorded after 6 hours of drug exposure and no growth was observed in almost all
      tested bacteria after 24 hours of exposure. No sign of toxidrome were observed
      during in vivo toxicity evaluation in mice at 300 mg/kg concentration.
      CONCLUSION: In conclusion, the present study provides the scientific rational for
      medicinal use of Lawsonia inermis. The use of Lawsonia inermis extracts is of
      great significance as substitute antimicrobial agent in therapeutics.

PMID- 24289299
TI  - Epithelium percentage estimation facilitates epithelial quantitative protein
      measurement in tissue specimens.
AB  - BACKGROUND: The rapid advancement of high-throughput tools for quantitative
      measurement of proteins has demonstrated the potential for the identification of
      proteins associated with cancer. However, the quantitative results on cancer
      tissue specimens are usually confounded by tissue heterogeneity, e.g. regions
      with cancer usually have significantly higher epithelium content yet lower
      stromal content. OBJECTIVE: It is therefore necessary to develop a tool to
      facilitate the interpretation of the results of protein measurements in tissue
      specimens. METHODS: Epithelial cell adhesion molecule (EpCAM) and cathepsin L
      (CTSL) are two epithelial proteins whose expressions in normal and tumorous
      prostate tissues were confirmed by measuring staining intensity with
      immunohistochemical staining (IHC). The expressions of these proteins were
      measured by ELISA in protein extracts from OCT embedded frozen prostate tissues.
      To eliminate the influence of tissue heterogeneity on epithelial protein
      quantification measured by ELISA, a color-based segmentation method was developed
      in-house for estimation of epithelium content using H&E histology slides from the
      same prostate tissues and the estimated epithelium percentage was used to
      normalize the ELISA results. The epithelium contents of the same slides were also
      estimated by a pathologist and used to normalize the ELISA results. The computer
      based results were compared with the pathologist's reading. RESULTS: We found
      that both EpCAM and CTSL levels, measured by ELISA assays itself, were greatly
      affected by epithelium content in the tissue specimens. Without adjusting for
      epithelium percentage, both EpCAM and CTSL levels appeared significantly higher
      in tumor tissues than normal tissues with a p value less than 0.001. However,
      after normalization by the epithelium percentage, ELISA measurements of both
      EpCAM and CTSL were in agreement with IHC staining results, showing a significant
      increase only in EpCAM with no difference in CTSL expression in cancer tissues.
      These results were obtained with normalization by both the computer estimated and
      pathologist estimated epithelium percentage. CONCLUSIONS: Our results show that
      estimation of tissue epithelium percentage using our color-based segmentation
      method correlates well with pathologists' estimation of tissue epithelium
      percentages. The epithelium contents estimated by color-based segmentation may be
      useful in immuno-based analysis or clinical proteomic analysis of tumor proteins.
      The codes used for epithelium estimation as well as the micrographs with
      estimated epithelium content are available online.

PMID- 24289298
TI  - Essential literature for the chiropractic profession: a survey of chiropractic
      research leaders.
AB  - BACKGROUND: Evidence-based clinical practice (EBCP) is an accepted practice for
      informed clinical decision making in mainstream health care professions. EBCP
      augments clinical experience and can have far reaching effects in education,
      policy, reimbursement and clinical management. The proliferation of published
      research can be overwhelming-finding a mechanism to identify literature that is
      essential for practitioners and students is desirable. The purpose of this study
      was to survey leaders in the chiropractic profession on their opinions of
      essential literature for doctors of chiropractic, faculty, and students to read
      or reference. METHODS: Deployment of an IRB exempted survey occurred with 68
      academic and research leaders using SurveyMonkey(r). Individuals were solicited
      via e-mail in August of 2011; the study closed in October of 2011. RESULTS: Forty
      three (43) individuals consented to participate; seventeen (17) contributed at
      least one article of importance. A total of 41 unique articles were reported. Of
      the six articles contributed more than once, one article was reported 6 times,
      and 5 were reported twice. CONCLUSIONS: A manageable list of relevant literature
      was created. Shortcomings of methods were identified, and improvements for
      continued implementation are suggested. A wide variety of articles were reported
      as "essential" knowledge; annual or bi-annual surveys would be helpful for the
      profession.

PMID- 24289300
TI  - Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a
      case-control study in Japanese women.
AB  - BACKGROUND: Lifestyle factors, including food and nutrition, physical activity,
      body composition and reproductive factors, and single nucleotide polymorphisms
      (SNPs) are associated with breast cancer risk, but few studies of these factors
      have been performed in the Japanese population. Thus, the goals of this study
      were to validate the association between reported SNPs and breast cancer risk in
      the Japanese population and to evaluate the effects of SNP genotypes and
      lifestyle factors on breast cancer risk. METHODS: A case-control study in 472
      patients and 464 controls was conducted from December 2010 to November 2011.
      Lifestyle was examined using a self-administered questionnaire. We analyzed 16
      breast cancer-associated SNPs based on previous GWAS or candidate-gene
      association studies. Age or multivariate-adjusted odds ratios (OR) and 95%
      confidence intervals (95% CI) were estimated from logistic regression analyses.
      RESULTS: High BMI and current or former smoking were significantly associated
      with an increased breast cancer risk, while intake of meat, mushrooms, yellow and
      green vegetables, coffee, and green tea, current leisure-time exercise, and
      education were significantly associated with a decreased risk. Three SNPs were
      significantly associated with a breast cancer risk in multivariate analysis:
      rs2046210 (per allele OR=1.37 [95% CI: 1.11-1.70]), rs3757318 (OR=1.33[1.05
      1.69]), and rs3803662 (OR=1.28 [1.07-1.55]). In 2046210 risk allele carriers,
      leisure-time exercise was associated with a significantly decreased risk for
      breast cancer, whereas current smoking and high BMI were associated with a
      significantly decreased risk in non-risk allele carriers. CONCLUSION: In Japanese
      women, rs2046210 and 3757318 located near the ESR1 gene are associated with a
      risk of breast cancer, as in other Asian women. However, our findings suggest
      that exercise can decrease this risk in allele carriers.

PMID- 24289301
TI  - In vitro precision of fit of computer-aided designed and computer-aided
      manufactured titanium screw-retained fixed dental prostheses before and after
      ceramic veneering.
AB  - OBJECTIVE: To compare the precision of fit of full-arch implant-supported screw
      retained computer-aided designed and computer-aided manufactured (CAD/CAM)
      titanium-fixed dental prostheses (FDP) before and after veneering. The null
      hypothesis was that there is no difference in vertical microgap values between
      pure titanium frameworks and FDPs after porcelain firing. MATERIALS AND METHODS:
      Five CAD/CAM titanium grade IV frameworks for a screw-retained 10-unit implant
      supported reconstruction on six implants (FDI tooth positions 15, 13, 11, 21, 23,
      25) were fabricated after digitizing the implant platforms and the cuspid
      supporting framework resin pattern with a laser scanner (CARES((r)) Scan CS2;
      Institut Straumann AG, Basel, Switzerland). A bonder, an opaquer, three layers of
      porcelain, and one layer of glaze were applied (Vita Titankeramik) and fired
      according to the manufacturer's preheating and fire cycle instructions at 400-800
      degrees C. The one-screw test (implant 25 screw-retained) was applied before and
      after veneering of the FDPs to assess the vertical microgap between implant and
      framework platform with a scanning electron microscope. The mean microgap was
      calculated from interproximal and buccal values. Statistical comparison was
      performed with non-parametric tests. RESULTS: All vertical microgaps were
      clinically acceptable with values <90 MUm. No statistically significant pairwise
      difference (P = 0.98) was observed between the relative effects of vertical
      microgap of unveneered (median 19 MUm; 95% CI 13-35 MUm) and veneered FDPs (20
      MUm; 13-31 MUm), providing support for the null-hypothesis. Analysis within the
      groups showed significantly different values between the five implants of the
      FDPs before (P = 0.044) and after veneering (P = 0.020), while a monotonous trend
      of increasing values from implant 23 (closest position to screw-retained implant
      25) to 15 (most distant implant) could not be observed (P = 0.169, P = 0.270).
      CONCLUSIONS: Full-arch CAD/CAM titanium screw-retained frameworks have a high
      accuracy. Porcelain firing procedure had no impact on the precision of fit of the
      final FDPs. All implant microgap measurements of each FDP showed clinically
      acceptable vertical misfit values before and after veneering. Thus, the results
      do not only show accurate performance of the milling and firing but show also a
      reproducible scanning and designing process.

PMID- 24289302
TI  - Comparative transcriptome analysis of tomato (Solanum lycopersicum) in response
      to exogenous abscisic acid.
AB  - BACKGROUND: Abscisic acid (ABA) can regulate the expressions of many stress
      responsive genes in plants. However, in defense responses to pathogens, mounting
      evidence suggests that ABA plays variable roles. Little information exists about
      genome-wide gene expression in ABA responses in tomato (Solanum lycopersicum L.),
      a model fruit crop plant. RESULTS: Global transcriptome profiles of tomato leaf
      responses to exogenous ABA were generated using Illumina RNA-sequencing. More
      than 173 million base pair reads were mapped onto the tomato reference genome and
      the expression pattern differences between treated and control leaves were
      assessed. In total, 50,616 transcripts were generated. Among them, 42,583 were
      functionally annotated in the NCBI non-redundant database and 47,877 in the
      tomato genome reference. Additionally, 31,107 transcripts were categorized into
      57 functional groups based on Gene Ontology terms, and 14,371 were assigned to
      310 Kyoto Encyclopedia of Genes and Genomes pathways. In both the ABA treatment
      and control samples, 39,671 transcripts were available to analyze their
      expressions, of which 21,712 (54.73%) responded to exogenous ABA. Of these
      transcripts, 2,787 were significantly differently expressed genes (DEGs). Many
      known and novel ABA-induced and -repressed genes were found. Exogenous ABA can
      influence the ABA signaling pathway with PYR/PYL/RCARs-PP2Cs-SnRK2s as the
      center. Eighteen PYL genes were detected. A large number of genes related to
      various transcription factors, heat shock proteins, pathogen resistance, and the
      salicylic acid, jasmonic acid, and ethylene signaling pathways were up-regulated
      by exogenous ABA. CONCLUSIONS: The results indicated that ABA has the potential
      to improve pathogen-resistance and abiotic stress tolerance in tomato. This study
      presents the global expression analysis of ABA-regulated transcripts in tomato
      and provides a robust database for investigating the functions of genes induced
      by ABA.

PMID- 24289304
TI  - How many days of accelerometer monitoring predict weekly physical activity
      behaviour in obese youth?
AB  - The aim of this study was to determine the type and the number of accelerometer
      monitoring days needed to predict weekly sedentary behaviour and physical
      activity in obese youth. Fifty-three obese youth wore a triaxial accelerometer
      for 7 days to measure physical activity in free-living conditions. Analyses of
      variance for repeated measures, Intraclass coefficient (ICC) and regression
      linear analyses were used. Obese youth spent significantly less time in physical
      activity on weekends or free days compared with school days. ICC analyses
      indicated a minimum of 2 days is needed to estimate physical activity behaviour.
      ICC were 0.80 between weekly physical activity and weekdays and 0.92 between
      physical activity and weekend days. The model has to include a weekday and a
      weekend day. Using any combination of one weekday and one weekend day, the
      percentage of variance explained is >90%. Results indicate that 2 days of
      monitoring are needed to estimate the weekly physical activity behaviour in obese
      youth with an accelerometer. Our results also showed the importance of taking
      into consideration school day versus free day and weekday versus weekend day in
      assessing physical activity in obese youth.

PMID- 24289303
TI  - Patient reported barriers and facilitators to using a self-management booklet for
      hip and knee osteoarthritis in primary care: results of a qualitative interview
      study.
AB  - BACKGROUND: To enhance guideline-based non-surgical management of hip or knee
      osteoarthritis (OA), a multidisciplinary, stepped-care strategy has been
      implemented in primary care in a region of the Netherlands. To facilitate this
      implementation, the self-management booklet "Care for Osteoarthritis" was
      developed and introduced. The aim of the booklet was to educate patients about
      OA, to enhance the patient's active role in the treatment course, and to improve
      the communication with health care providers. To successfully introduce the
      booklet on a large scale we assessed barriers and facilitators for patients to
      using this booklet. METHODS: Seventeen primary care patients with hip or knee OA
      who received the self-management booklet participated in this qualitative study
      using semi-structured interviews. Purposive sampling was used to ensure diversity
      of the patients' view about the booklet. The interviews were transcribed verbatim
      and analysed using a thematic analysis approach. RESULTS: Three core themes with
      patient perceived barriers and facilitators to use the booklet emerged from the
      interviews: 1) the role of health care providers, 2) the patient's perceptions
      about OA and its manageability, and 3) the patient's perceptions about the
      usefulness of the booklet and patient's information needs. Regarding the first
      theme, a barrier was the lack of encouragement from health care providers to use
      the booklet in the treatment course of OA. Moreover, patients had doubts
      concerning the health care providers' endorsement of non-surgical treatment for
      OA. Barriers from the second theme were: thinking that OA is not treatable or
      that being pro-active during the treatment course is not important. In contrast,
      being convinced about the importance of an active participation in the treatment
      course was a facilitator. Third, patients' perceptions about the usefulness of
      the booklet and patients' information needs were both identified as barriers as
      well as facilitators for booklet use. CONCLUSIONS: This study contributes to the
      understanding of patient perceived barriers and facilitators to use a self
      management booklet in the treatment course of OA. The results offer practical
      starting points to tailor the implementation activities of the booklet nationwide
      and to introduce comparable educational tools in OA primary care or in other
      chronic diseases.

PMID- 24289305
TI  - Structure-based evaluation of C5 derivatives in the catechol diether series
      targeting HIV-1 reverse transcriptase.
AB  - Using a computationally driven approach, a class of inhibitors with picomolar
      potency known as the catechol diethers were developed targeting the non
      nucleoside-binding pocket of HIV-1 reverse transcriptase. Computational studies
      suggested that halogen-bonding interactions between the C5 substituent of the
      inhibitor and backbone carbonyl of conserved residue Pro95 might be important.
      While the recently reported crystal structures of the reverse transcriptase
      complexes confirmed the interactions with the non-nucleoside-binding pocket, they
      revealed the lack of a halogen-bonding interaction with Pro95. To understand the
      effects of substituents at the C5 position, we determined additional crystal
      structures with 5-Br and 5-H derivatives. Using comparative structural analysis,
      we identified several conformations of the ethoxy uracil dependent on the
      strength of a van der Waals interaction with the Cgamma of Pro95 and the C5
      substitution. The 5-Cl and 5-F derivatives position the ethoxy uracil to make
      more hydrogen bonds, whereas the larger 5-Br and smaller 5-H position the ethoxy
      uracil to make fewer hydrogen bonds. EC50 values correlate with the trends
      observed in the crystal structures. The influence of C5 substitutions on the
      ethoxy uracil conformation may have strategic value, as future derivatives can
      possibly be modulated to gain additional hydrogen-bonding interactions with
      resistant variants of reverse transcriptase. 

PMID- 24289306
TI  - Aromatic and hydrophobic surfaces of wood-derived biochar enhance perchlorate
      adsorption via hydrogen bonding to oxygen-containing organic groups.
AB  - The pH-dependent adsorption of perchlorate (ClO4(-)) by wood-derived biochars
      produced at 200-700  degrees C (referred as FB200-FB700) was investigated to
      probe the anion retention mechanisms of biochars and to identify the interactions
      of water and biochar. ClO4(-) adsorption was controlled by the surface polarities
      and structural compositions of the organic components of biochars, rather than
      their inorganic mineral components. FB500-FB700 biochars with low polarity and
      high aromaticity displayed a superior ClO4(-) adsorption capacity, but which was
      affected by solution pH. Besides electrostatic interaction, hydrogen bonding to
      oxygen-containing groups on biochars was proposed the dominant force for
      perchlorate adsorption, which led to the maximum adsorption occurring near pHIEP,
      where surface charge equals zero. The dissociation of these surface oxygen
      containing groups was monitored by zeta potential curves, which indicated that
      the H-bonds donors on biochar surface for ClO4(-) binding were changed from -COOH
      (ClO4(-)...HOOC-) and -OH (ClO4(-)...HO-) to -OH alone with an increase in pH.
      The H-bond force was strengthened by the condensed aromatic surfaces, since high
      temperature biochars provided a hydrophobic microenvironment to accommodate
      weakly hydrated perchlorate and facilitated the H-bonds for ClO4(-) binding to
      functional groups by the large pi subunit of their aromatic substrate. Lastly,
      the batch and column tests of ClO4(-) adsorption showed that biochars like FB700
      are effective adsorbents for anion pollutant removal via H-bonding interaction. 

PMID- 24289307
TI  - Prognostic accuracy of clinicians for back, neck and shoulder patients in routine
      practice.
AB  - BACKGROUND: Chronicity amongst musculoskeletal patients remains a considerable
      burden and predicting outcomes in these patients has proven difficult. Although a
      large number of studies have investigated a range of predictors of outcome few
      have looked at the practitioners' ability to discern those that improve from
      those most likely to fail to improve. This study aimed to investigate the ability
      of chiropractors to predict patient outcomes. METHODS: Prediction and outcome
      data were collected from 440 consecutive patients with back, neck or shoulder
      pain accepted for chiropractic care within 5 linked private practices.Predictions
      by chiropractors were compared to patient outcomes as measured by Bournemouth
      Questionnaire (BQ) scores, pain NRS scores and patient global impression of
      change (PGIC) collected at 4 and 12 weeks following the initial consultation.
      RESULTS: Overall, chiropractors appear unable to accurately predict poor outcomes
      in their patients particularly in the longer term. Although some conditions
      (neck) faired a little better in some cases with some trends in short term pain
      scores being associated with the clinicians prediction, this was marginal.
      Subgrouping by practitioners or duration did not improve the performance of these
      predictions CONCLUSIONS: Chiropractors generally fail to reliably predict poor
      treatment outcome of patients at initial consultation.

PMID- 24289309
TI  - Spontaneously regressing papules and nodules with alarming histology.

PMID- 24289308
TI  - An analysis of segmentation dynamics throughout embryogenesis in the centipede
      Strigamia maritima.
AB  - BACKGROUND: Most segmented animals add segments sequentially as the animal grows.
      In vertebrates, segment patterning depends on oscillations of gene expression
      coordinated as travelling waves in the posterior, unsegmented mesoderm. Recently,
      waves of segmentation gene expression have been clearly documented in insects.
      However, it remains unclear whether cyclic gene activity is widespread across
      arthropods, and possibly ancestral among segmented animals. Previous studies have
      suggested that a segmentation oscillator may exist in Strigamia, an arthropod
      only distantly related to insects, but further evidence is needed to document
      this. RESULTS: Using the genes even skipped and Delta as representative of genes
      involved in segment patterning in insects and in vertebrates, respectively, we
      have carried out a detailed analysis of the spatio-temporal dynamics of gene
      expression throughout the process of segment patterning in Strigamia. We show
      that a segmentation clock is involved in segment formation: most segments are
      generated by cycles of dynamic gene activity that generate a pattern of double
      segment periodicity, which is only later resolved to the definitive single
      segment pattern. However, not all segments are generated by this process. The
      most posterior segments are added individually from a localized sub-terminal area
      of the embryo, without prior pair-rule patterning. CONCLUSIONS: Our data suggest
      that dynamic patterning of gene expression may be widespread among the
      arthropods, but that a single network of segmentation genes can generate either
      oscillatory behavior at pair-rule periodicity or direct single segment
      patterning, at different stages of embryogenesis.

PMID- 24289310
TI  - Gold nanoparticles interfere with sperm functionality by membrane adsorption
      without penetration.
AB  - Abstract To examine gold nanoparticle reprotoxicity, bovine spermatozoa were
      challenged with ligand-free or oligonucleotide-conjugated gold nanoparticles
      synthesized purely without any surfactants by laser ablation. Sperm motility
      declined at nanoparticle mass dose of 10 ug/ml (corresponding to ~14 000
      nanoparticles per sperm cell) regardless of surface modification. Sperm
      morphology and viability remained unimpaired at all concentrations. Transmission
      electron microscopy showed an modification dependant attachment of nanoparticles
      to the cell membrane of spermatozoa, but provided no evidence for nanoparticle
      entrance into sperm cells. A molecular examination revealed a reduction of free
      thiol residues on the cell membrane after nanoparticle exposure, which could
      explain the decrease in sperm motility. Sperm fertilising ability decreased after
      exposure to 10 ug/ml of ligand-free nanoparticles indicating that agglomerated
      ligand-free nanoparticles interfere with membrane properties necessary for
      fertilisation. In conclusion, nanoparticles may impair key sperm functions solely
      by interacting with the sperm surface membrane. 

PMID- 24289311
TI  - Successful treatment of suprasellar tumors associated with poor brain blood
      perfusion by severe intracranial arterial stenosis: two case reports.
AB  - BACKGROUND: Treatment strategy to prevent perioperative cerebral infarction in
      patients with asymptomatic severe stenosis of the internal carotid artery is not
      fully established. CASE PRESENTATION: Two patients were treated for skull base
      tumor in the presence of severe stenosis of the internal carotid artery,
      unilateral in one patient and bilateral in the other patient. Both patients were
      asymptomatic but had reduced vascular reserve capacity. The extended
      transsphenoidal approach was planned avoiding the low perfusion pressure region,
      with only conventional methods of maintaining blood pressure and PaCO2 rather
      than performing prophylactic vascular reconstruction surgery, and successful
      tumor removals were achieved without causing further neurological or radiological
      deficits. CONCLUSION: If the surgical route is planned to avoid the distribution
      of stenotic vessels and low perfusion pressure, prophylactic vascular
      reconstruction surgery would be unnecessary. Although more experiences based on
      sub-classified etiology for internal carotid artery stenosis are required,
      various types of operations including intracranial-extracranial vascular surgery
      might be justified based on this principle.

PMID- 24289312
TI  - CBCT-based volumetric and dosimetric variation evaluation of volumetric modulated
      arc radiotherapy in the treatment of nasopharyngeal cancer patients.
AB  - OBJECTIVE: To investigate the anatomic and dosimetric variations of volumetric
      modulated arc therapy (VMAT) in the treatment of nasopharyngeal cancer (NPC)
      patients based on weekly cone beam CT (CBCT). MATERIALS AND METHODS: Ten NPC
      patients treated by VMAT with weekly CBCT for setup corrections were reviewed
      retrospectively. Deformed volumes of targets and organs at risk (OARs) in the
      CBCT were compared with those in the planning CT. Delivered doses were
      recalculated based on weekly CBCT and compared with the planned doses. RESULTS:
      No significant volumetric changes on targets, brainstem, and spinal cord were
      observed. The average volumes of right and left parotid measured from the fifth
      CBCT were about 4.4 and 4.5 cm3 less than those from the first CBCT,
      respectively. There were no significant dose differences between average planned
      and delivered doses for targets, brainstem and spinal cord. For right parotid,
      the delivered mean dose was 10.5 cGy higher (p = 0.004) than the planned value
      per fraction, and the V26 and V32 increased by 7.5% (p = 0.002) and 7.4% (p =
      0.01), respectively. For the left parotid, the D50 (dose to the 50% volume) was
      8.8 cGy higher (p = 0.03) than the planned values per fraction, and the V26
      increased by 8.8% (p = 0.002). CONCLUSION: Weekly CBCTs were applied directly to
      study the continuous volume changes and resulting dosimetric variations of
      targets and OARs for NPC patients undergoing VMAT. Significant volumetric and
      dosimetric variations were observed for parotids. Replanning after 30 Gy will
      benefit the protection on parotids.

PMID- 24289314
TI  - Phylogenetically related and ecologically similar carnivores harbour similar
      parasite assemblages.
AB  - Most parasites infect multiple hosts, but what factors determine the range of
      hosts a given parasite can infect? Understanding the broad scale determinants of
      parasite distributions across host lineages is important for predicting pathogen
      emergence in new hosts and for estimating pathogen diversity in understudied host
      species. In this study, we used a new data set on 793 parasite species reported
      from free-ranging populations of 64 carnivore species to examine the factors that
      influence parasite sharing between host species. Our results showed that
      parasites are more commonly shared between phylogenetically related host species
      pairs. Additionally, host species with higher similarity in biological traits and
      greater geographic range overlap were also more likely to share parasite species.
      Of three measures of phylogenetic relatedness considered here, the number
      divergence events that separated host species pairs most strongly influenced the
      likelihood of parasite sharing. We also showed that viruses and helminths tend to
      infect carnivore hosts within more restricted phylogenetic ranges than expected
      by chance. Overall, our results underscore the importance of host evolutionary
      history in determining parasite host range, even when simultaneously considering
      other factors such as host ecology and geographic distribution. 

PMID- 24289313
TI  - TGM3, a candidate tumor suppressor gene, contributes to human head and neck
      cancer.
AB  - BACKGROUND: In our previous study using oligonucleotide microarrays, we revealed
      that transglutaminase 3 (TGM3) was remarkably down-regulated in head and neck
      cancer (HNC). However, the potential of TGM3 as a useful biomarker or molecular
      target for HNC is unclear. METHODS: The transcriptional and post-translational
      status of TGM3 in HNC cell lines and specimens was detected using real-time PCR
      and western blot analysis. Bisulfate-treated DNA sequencing was used to analyze
      the molecular mechanism of TGM3 gene silencing. In addition, the effects of TGM3
      on the proliferation, colony formation and induction of apoptosis in vitro and
      tumorigenicity in vivo were investigated through exogenous expression of TGM3 in
      HNC cells. Immunohistochemistry was used to evaluate TGM3 expression in large HNC
      samples. RESULTS: TGM3 was down-regulated in HNC samples and cell lines (P <
      0.0001). The hypermethylation of a promoter CpG island was one of the mechanisms
      of silencing the TGM3 gene in HNC. Exogenous expression of TGM3 in HNC cells
      could inhibit the proliferation and enhance the apoptosis of HNC cells in vitro
      and suppress tumor growth in vivo. In addition, TGM3 protein levels were strongly
      associated with the pathological differentiation of HNC tissues (P = 0.0037).
      Survival analysis revealed that low TGM3 expression was associated with worse
      overall survival (P = 0.0002), and TGM3 expression level was an independent
      predictor in patients with HNC. CONCLUSIONS: The studies prove that TGM3, as a
      candidate tumor suppressor, contributes to the carcinogenesis and development of
      HNC and may serve as a useful biomarker for patients with HNC.

PMID- 24289315
TI  - Benzocaine complexation with p-sulfonic acid calix[n]arene: experimental ((1) H
      NMR) and theoretical approaches.
AB  - The aim of this work was to study the interaction between the local anesthetic
      benzocaine and p-sulfonic acid calix[n]arenes using NMR and theoretical
      calculations and to assess the effects of complexation on cytotoxicity of
      benzocaine. The architectures of the complexes were proposed according to (1) H
      NMR data (Job plot, binding constants, and ROESY) indicating details on the
      insertion of benzocaine in the cavity of the calix[n]arenes. The proposed
      inclusion compounds were optimized using the PM3 semiempirical method, and the
      electronic plus nuclear repulsion energy contributions were performed at the DFT
      level using the PBE exchange/correlation functional and the 6-311G(d) basis set.
      The remarkable agreement between experimental and theoretical approaches adds
      support to their use in the structural characterization of the inclusion
      complexes. In vitro cytotoxic tests showed that complexation intensifies the
      intrinsic toxicity of benzocaine, possibly by increasing the water solubility of
      the anesthetic and favoring its partitioning inside of biomembranes. 

PMID- 24289316
TI  - Diet and exercise effects on aerobic fitness and body composition in seriously
      mentally ill adults.
AB  - Low exercise capacity and high obesity levels are the main characteristics of
      people with serious mental illness (SMI). We conducted a pilot study on the
      effects of a 3-month exercise and dietary intervention on the aerobic capacity
      and body composition of obese adults with SMI taking Olanzapine, a second
      generation antipsychotic medication known to induce weight increments. Fifty
      adults with SMI (15 males and 35 females) followed a 3-month weight loss
      intervention programme based on exercise and diet. Pre- and post-intervention, a
      submaximal [Formula: see text]O2 exercise test was performed in order to assess
      [Formula: see text]O2max anthropometric and body composition measurements were
      also performed. All participants were obese (body mass index (BMI): 33.61 +/-
      0.91 kg/m(2)). Pre- and post-intervention, a submaximal [Formula: see text]O2
      exercise test on the treadmill was performed in order to assess [Formula: see
      text]O2max anthropometric and body composition measurements were also performed.
      Significant reductions in body weight, BMI, body fat and waist circumference were
      found from pre to post (p < 0.01). [Formula: see text]O2max was significantly
      improved in both genders (males: pre: 30.63 +/- 2.06 vs. post: 33.19 +/- 1.77
      ml(.)kg(-1) min(-1), females: pre: 25.93 +/- 1.01 vs. post: 29.51 +/- 1.06
      ml(.)kg(-1) min(-1), p < 0.01). A significant correlation was found between the
      change in [Formula: see text]O2max and the change in body weight and BMI (p <
      0.05). Multiple regression analysis revealed that the relative change in
      [Formula: see text]O2max explained approximately 26% of the variance in the
      changes for both BMI (p = 0.07) and body weight (p = 0.06). A treatment of
      exercise and diet improves the aerobic capacity and body composition of obese
      adults with SMI, despite the use of Olanzapine.

PMID- 24289317
TI  - Observation of single electron transport via multiple quantum states of a silicon
      quantum dot at room temperature.
AB  - Single electron transport through multiple quantum levels is realized in a Si
      quantum-dot device at room-temperature conditions. The energy spacing of more
      than triple the omnipresent thermal energy is obtained from an extremely small
      ellipsoidal Si quantum dot, and high charge stability is attained through a
      construction of the gate-all-around structure. These properties may move us a
      step closer to practical applications of quantum devices at elevated
      temperatures. An in-depth analysis on the transport behavior and quantum
      structure is presented. 

PMID- 24289318
TI  - Where should we operate on the preterm neonate?
AB  - The ideal venue for neonatal surgical procedures has been the subject of a
      contentious debate between the leading pediatric hospitals throughout the world.
      Bias toward the location of neonatal surgery tends to be based on institutional
      practices. The following opposing viewpoints from two leading pediatric
      institutions in the United Kingdom and the United States highlight the relevant
      issues. 

PMID- 24289319
TI  - Adenosine-to-inosine RNA editing and human disease.
AB  - A-to-I RNA editing is a post-transcriptional modification that converts
      adenosines to inosines in both coding and noncoding RNA transcripts. It is
      catalyzed by ADAR (adenosine deaminase acting on RNA) enzymes, which exist
      throughout the body but are most prevalent in the central nervous system.
      Inosines exhibit properties that are most similar to those of guanosines. As a
      result, ADAR-mediated editing can post-transcriptionally alter codons, introduce
      or remove splice sites, or affect the base pairing of the RNA molecule with
      itself or with other RNAs. A-to-I editing is a mechanism that regulates and
      diversifies the transcriptome, but the full biological significance of ADARs is
      not understood. ADARs are highly conserved across vertebrates and are essential
      for normal development in mammals. Aberrant ADAR activity has been associated
      with a wide range of human diseases, including cancer, neurological disorders,
      metabolic diseases, viral infections and autoimmune disorders. ADARs have been
      shown to contribute to disease pathologies by editing of glutamate receptors,
      editing of serotonin receptors, mutations in ADAR genes, and by other mechanisms,
      including recently identified regulatory roles in microRNA processing. Advances
      in research into many of these diseases may depend on an improved understanding
      of the biological functions of ADARs. Here, we review recent studies
      investigating connections between ADAR-mediated RNA editing and human diseases. 

PMID- 24289320
TI  - Content analysis of medical students' seminars: a unique method of analyzing
      clinical thinking.
AB  - BACKGROUND: The study of communication skills of Asian medical students during
      structured Problem-based Learning (PBL) seminars represented a unique opportunity
      to assess their critical thinking development. This study reports the first
      application of the health education technology, content analysis (CA), to a
      Japanese web-based seminar (webinar). METHODS: The authors assigned twelve
      randomly selected medical students from two universities and two clinical
      instructors to two virtual classrooms for four PBL structured tutoring sessions
      that were audio-video captured for CA. Both of the instructors were US-trained
      physicians. This analysis consisted of coding the students' verbal comments into
      seven types, ranging from trivial to advanced knowledge integration comments that
      served as a proxy for clinical thinking. RESULTS: The most basic level of verbal
      simple responses accounted for a majority (85%) of the total students' verbal
      comments. Only 15% of the students' comments represented more advanced types of
      critical thinking. The male students responded more than the female students;
      male students attending University 2 responded more than male students from
      University 1. The total mean students' verbal response time for the four sessions
      with the male instructor was 6.9%; total mean students' verbal response time for
      the four sessions with the female instructor was 19% (p < 0.05). CONCLUSIONS:
      This report is the first to describe the application of CA to a multi-university
      real time audio and video PBL medical student clinical training webinar in two
      Japanese medical schools. These results are preliminary, mostly limited by a
      small sample size (n = 12) and limited time frame (four sessions). CA technology
      has the potential to improve clinical thinking for medical students. This report
      may stimulate improvements for implementation.

PMID- 24289321
TI  - Associations between occupational indicators and total, work-based and leisure
      time sitting: a cross-sectional study.
AB  - BACKGROUND: A better understanding of how occupational indicators (e.g. job type,
      doing shift-work, hours worked, physical demand) influence sitting time will aid
      in the design of more effective health behaviour interventions. The aim of the
      study was to examine the associations between several occupational indicators and
      total, occupational and leisure-time sitting. METHODS: Cross-sectional self
      report data was collected in November 2011 from 1194 participants through a
      telephone interview in regional Queensland, Australia (response rate was 51.9%).
      The Workforce Sitting Questionnaire was used to measure sitting time. Multiple
      logistic regression was applied to examine associations between sitting time and
      occupational indicators. RESULTS: Of all participants 77.9% were employed full
      time, 72.7% had white-collar jobs, 35.7% were engaged in shift-work, 39.5% had
      physically demanding jobs, and 53.2% had high total sitting time (>8 hours a
      day). Those in physically demanding and blue-collar occupations were less likely
      to report high total (physically demanding: OR = 0.41,95% CI = 0.29-0.58; blue
      collar: OR = 0.55,95% CI = 0.37-0.82) and occupational (physically demanding: OR
      = 0.26,95% CI = 0.14-0.24; blue-collar: OR = 0.32,95% CI = 0.21-0.49) sitting
      time compared to those in physically undemanding and white-collar occupations
      respectively. Working more than 8 hours per day was inversely associated with
      high leisure-time sitting (OR = 0.44,95% CI = 0.29-0.68). No evidence for
      'compensation' effects, where lower occupational sitting is compensated with
      higher leisure-time sitting, was found. CONCLUSIONS: Behaviour change
      interventions are needed to reduce sitting time as a means to prevent chronic
      disease. Workplace initiatives to reduce sitting time may be particularly
      important among individuals employed in white-collar and physical undemanding
      occupations, although other intervention strategies targeting leisure-time
      sitting are also required.

PMID- 24289322
TI  - Regional difference in sebum production by androgen susceptibility in human
      facial skin.
AB  - Androgens are important hormones that influence sebum production from the
      sebaceous glands. Human facial skin can be categorized as T- and U-zones, which
      are areas with high and low levels of sebum secretion, respectively. This study
      was performed to investigate whether there are topographical differences in
      androgen receptor (AR) expression related to regional variations in facial sebum
      secretion. The results of in vivo analysis indicated a statistically significant
      increase in AR expression in the sebaceous gland T-zones compared with the U
      zones. In vitro experiments using human primary sebocytes also yielded similar
      results, with higher levels of AR protein and mRNA expression in T-zones. The
      results of this study suggested that differences in androgen susceptibility may
      be an important factor influencing regional differences in sebum production in
      human facial skin. 

PMID- 24289323
TI  - Economical and accurate protocol for calculating hydrogen-bond-acceptor
      strengths.
AB  - A series of density functional/basis set combinations and second-order Moller
      Plesset calculations have been used to test their ability to reproduce the trends
      observed experimentally for the strengths of hydrogen-bond acceptors in order to
      identify computationally efficient techniques for routine use in the
      computational drug-design process. The effects of functionals, basis sets,
      counterpoise corrections, and constraints on the optimized geometries were tested
      and analyzed, and recommendations (M06-2X/cc-pVDZ and X3LYP/cc-pVDZ with single
      point counterpoise corrections or X3LYP/aug-cc-pVDZ without counterpoise) were
      made for suitable moderately high-throughput techniques. 

PMID- 24289324
TI  - Parents' and clinicians' views of an interactive booklet about respiratory tract
      infections in children: a qualitative process evaluation of the EQUIP randomised
      controlled trial.
AB  - BACKGROUND: 'When should I worry?' is an interactive booklet for parents of
      children presenting with respiratory tract infections (RTIs) in primary care and
      associated training for clinicians. A randomised controlled trial (the EQUIP
      study) demonstrated that this intervention reduced antibiotic prescribing and
      future consulting intentions. The aims of this qualitative process evaluation
      were to understand how acceptable the intervention was to clinicians and parents,
      how it was implemented, the mechanisms for any observed effects, and contextual
      factors that could have influenced its effects. METHODS: Semi-structured
      interviews were conducted with 20 parents and 13 clinicians who participated in
      the trial. Interviews were audio-recorded and transcribed verbatim. Data were
      analysed using a framework approach, which involved five stages; familiarisation,
      development of a thematic framework, indexing, charting, and interpretation.
      RESULTS: Most parents and clinicians reported that the 'When should I worry'
      interactive booklet (and online training for clinicians) was easy to use and
      valuable. Information on recognising signs of serious illness and the usual
      duration of illness were most valued. The interactive use of the booklet during
      consultations was considered to be important, but this did not always happen.
      Clinicians reported lack of time, lack of familiarity with using the booklet, and
      difficulty in modifying their treatment plan/style of consultation as barriers to
      use. Increased knowledge and confidence amongst clinicians and patients were seen
      as key components that contributed to the reductions in antibiotic prescribing
      and intention to consult seen in the trial. This was particularly pertinent in a
      context where decisions about the safe and appropriate management of childhood
      RTIs were viewed as complex and parents reported frequently receiving
      inconsistent messages. CONCLUSIONS: The 'When should I worry' booklet, which is
      effective in reducing antibiotic prescribing, has high acceptability for
      clinicians and parents, helps address gaps in knowledge, increases confidence,
      and provides a consistent message. However, it is not always implemented as
      intended. Plans for wider implementation of the intervention in health care
      settings would need to address clinician-related barriers to implementation.
      TRIAL REGISTRATION: ISRCTN46104365.

PMID- 24289326
TI  - A new germline mutation in KIT associated with diffuse cutaneous mastocytosis in
      a Chinese family.
AB  - Diffuse cutaneous mastocytosis (DCM) is an extremely rare disease characterized
      by massive proliferation of mast cells infiltrating the entire skin. We report a
      Chinese family with indolent DCM, and detection of a new germline KIT mutation
      located in the fifth immunoglobulin-like loop of the KIT protein, which probably
      results in a gain-of-function effect and consequent overactivation of mast cells.
      Our report expands the knowledge of correlations between the genotype of KIT
      mutations and the phenotype of DCM. 

PMID- 24289325
TI  - Morphogenesis-regulated localization of protein kinase A to genomic sites in
      Candida albicans.
AB  - BACKGROUND: The human fungal pathogen Candida albicans is able to undergo
      morphogenesis from a yeast to a hyphal growth form. Protein kinase A (PKA)
      isoforms Tpk1 and Tpk2 promote hyphal growth in a signalling pathway via the
      transcription factor Efg1. RESULTS: C. albicans strains producing epitope-tagged
      Tpk1 or Tpk2 were used in genome-wide chromatin immunoprecipitation on chip (ChIP
      chip) to reveal genomic binding sites. During yeast growth, both PKA isoforms
      were situated primarily within ORFs but moved to promoter regions shortly after
      hyphal induction. Binding sequences for Tpk2 greatly exceeded Tpk1 sites and did
      not coincide with binding of the PKA regulatory subunit Bcy1. Consensus binding
      sequences for Tpk2 within ORFs included ACCAC and CAGCA motifs that appeared to
      bias codon usage within the binding regions. Promoter residency of Tpk2
      correlated with the transcript level of the corresponding gene during hyphal
      morphogenesis and occurred near Efg1 binding sites, mainly on genes encoding
      regulators of morphogenesis. CONCLUSIONS: PKA isoforms change their genomic
      binding sites from ORF to promoter regions during yeast-hyphal morphogenesis.
      Tpk2 binds preferentially to promoters of genes encoding regulators of cellular
      morphogenesis.

PMID- 24289327
TI  - Denosumab in osteoporosis.
AB  - INTRODUCTION: Denosumab is a fully human monoclonal antibody against the receptor
      activator of nuclear factor kappa-B ligand. It is an antiresorptive agent that
      reduces osteoclastogenesis. AREAS COVERED: This drug evaluation reviews denosumab
      for use in osteoporosis. Denosumab has been shown to improve bone mineral density
      (BMD) and to reduce the incidence of new vertebral, hip and nonvertebral
      fractures in postmenopausal women. It prevents bone loss and reduces vertebral
      fracture risk in men with nonmetastatic prostate cancer who are receiving
      androgen deprivation therapy. It has also been shown to improve BMD in men with
      osteoporosis unrelated to androgen deprivation therapy. Safety concerns include
      infections, cancer, skin reactions, cardiovascular disease, hypocalcemia,
      osteonecrosis of the jaw and atypical femur fractures. EXPERT OPINION: Although
      bisphosphonates are typically preferred as initial therapy for osteoporosis,
      denosumab could be used as initial therapy in select patients at high risk for
      fracture, including older patients who have difficulty with the dosing
      requirements of oral bisphosphonates, patients who are intolerant of or
      unresponsive to other therapies, and in those with impaired renal function.
      Additional data is needed to address issues regarding treatment duration and
      discontinuation, as well as to provide more information regarding denosumab's
      efficacy and safety.

PMID- 24289329
TI  - Aluminum affects heterogeneous Fe(III) (Hydr)oxide nucleation, growth, and
      ostwald ripening.
AB  - Heterogeneous coprecipitation of iron and aluminum oxides is an important process
      for pollutant immobilization and removal in natural and engineered aqueous
      environments. Here, using a synchrotron-based small-angle X-ray scattering
      technique, we studied heterogeneous nucleation and growth of Fe(III) (hydr)oxide
      on quartz under conditions found in acid mine drainage (at pH = 3.7 +/- 0.2,
      [Fe(3+)] = 10(-4) M) with different initial aqueous Al/Fe ratios (0:1, 1:1, and
      5:1). Interestingly, although the atomic ratios of Al/Fe in the newly formed
      Fe(III) (hydr)oxide precipitates were less than 1%, the in situ particle size and
      volume evolutions of the precipitates on quartz were significantly influenced by
      aqueous Al/Fe ratios. At the end of the 3 h experiments, with aqueous Al/Fe
      ratios of 0:1, 1:1, and 5:1, the average radii of gyration of particles on quartz
      were 5.7 +/- 0.3, 4.6 +/- 0.1, and 3.7 +/- 0.3 nm, respectively, and the ratio of
      total particle volumes on quartz was 1.7:3.4:1.0. The Fe(III) (hydr)oxide
      precipitates were poorly crystallized, and were positively charged in all
      solutions. In the presence of Al(3+), Al(3+) adsorption onto quartz changed the
      surface charge of quartz from negative to positive, which caused the slower
      heterogeneous growth of Fe(III) (hydr)oxide on quartz. Furthermore, Al affected
      the amount of water included in the Fe(III) (hydr)oxides, which can influence
      their adsorption capacity. This study yielded important information usable for
      pollutant removal not only in natural environments, but also in engineered water
      treatment processes. 

PMID- 24289328
TI  - Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based
      diagnosis of colorectal cancer.
AB  - BACKGROUND: DNA methylation is a well-known epigenetic mechanism involved in
      epigenetic gene regulation. Several genes were reported hypermethylated in CRC,
      althought no gene marker was proven to be individually of sufficient sensitivity
      or specificity in routine clinical practice. Here, we identified novel epigenetic
      markers and assessed their combined use for diagnostic accuracy. METHODS: We used
      methylation arrays on samples from several effluents to characterize methylation
      profiles in CRC samples and controls, as established by colonoscopy and pathology
      findings, and selected two differentially methylated candidate epigenetic genes
      (NPY, PENK). To this gene panel we added WIF, on the basis of being reported in
      literature as silenced by promoter hypermethylation in several cancers, including
      CRC. We measured their methylation degrees by quantitative multiplex-methylation
      specific PCR (QM-MSP) on 15 paired carcinomas and adjacent non-cancerous
      colorectal tissues and we subsequently performed a clinical validation on two
      different series of 266 serums, subdivided in 32 CRC, 26 polyps, 47 other cancers
      and 161 with normal colonoscopy. We assessed the results by receiver operating
      characteristic curve (ROC), using cumulative methylation index (CMI) as variable
      threshold. RESULTS: We obtained CRC detection on tissues with both sensitivity
      and specificity of 100%. On serum CRC samples, we obtained
      sensitivity/specificity values of, e.g., 87%/80%, 78%/90% and 59%/95%, and
      negative predictive value/positive predictive value figures of 97%/47%, 95%/61%
      and 92%/70%. On serum samples from other cancers we obtained
      sensitivity/specificity of, e.g, 89%/25%, 43%/80% and 28%/91%. CONCLUSIONS: We
      showed the potential of NPY, PENK, and WIF1 as combined epigenetic markers for
      CRC diagnosis, both in tissue and serum and tested their use as serum biomarkers
      in other cancers. We optimized a QM-MSP for simultaneously quantifying their
      methylation levels. Our assay can be an effective blood test for patients where
      CRC risk is present but difficult to assess (e.g. mild symptoms with no CRC
      family history) and who would therefore not necessarily choose to go for further
      examination. This panel of markers, if validated, can also be a cost effective
      screening tool for the detection of asymptomatic cancer patients for colonoscopy.

PMID- 24289330
TI  - FoxO3a modulation and promotion of apoptosis by interferon-alpha2b in rat
      preneoplastic liver.
AB  - BACKGROUND: FoxO3a, a member of the FOXO family of transcription factors, is
      expressed in adult liver and modulates the expression of genes involved in
      apoptosis. FoxO3a is post-translationally regulated, negatively by PI3K/Akt and
      MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we
      have demonstrated that interferon-alpha2b (IFN-alpha2b) induces apoptosis of
      hepatic preneoplastic foci through the production of reactive oxygen species
      (ROS). AIMS: To investigate the post-translational signal events triggered by the
      oxidative stress induced by IFN-alpha2b and the modulation of FoxO3a
      transcriptional activity during these events in rat preneoplastic liver. METHODS:
      Adult male Wistar rats were subjected to a two-phase model of
      hepatocarcinogenesis. A group of animals received IFN-alpha2b and another group
      received IFN-alpha2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid
      peroxidation, immunohistochemistry, immunoblotting, co-immunoprecipitation and
      sqRT-PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a,
      beta-catenin and PUMA in the IFN-alpha2b-mediated apoptotic mechanism. RESULTS:
      In vivo IFN-alpha2b treatment induced endogenous production of ROS which
      activated JNK. IFN-alpha2b blocked the activation of Akt and Erk, avoiding FoxO3a
      activity repression. Activated JNK was responsible for the nuclear translocation
      and transcriptional activity of FoxO3a which positively modulated the expression
      of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the
      nuclear beta-catenin associated to TCF, inhibiting the canonical Wnt signalling
      pathway. CONCLUSIONS: The data presented here propose a model in which in vivo
      IFN-alpha2b treatment induces nuclear translocation and transcriptional activity
      of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic
      preneoplastic foci.

PMID- 24289331
TI  - Studying nanoparticle interaction with human placenta: Festina lente!

PMID- 24289332
TI  - Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2
      enriched electrolyzed water.
AB  - Recent studies have revealed the biological effects of H2 in suppressing organ
      injuries due to acute inflammation and oxidative stress. Dahl salt-sensitive (SS)
      rats naturally develop elevated blood pressure (BP) and kidney injury with aging.
      The present study examined the effect of long-term supplementation of H2 in
      drinking water on age-related changes.Four-week-old male Dahl SS rats were fed 3
      types of water (n = 30 each) for up to 48 weeks: filtered water (FW), water with
      a high H2 content (492.5 ppb) obtained with water electrolysis (EW), or
      dehydrogenated EW (DW). Animals were subjected to histological analysis at 16,
      24, and 48 weeks.The FW group showed progressive BP elevation and increases in
      albuminuria and cardiac remodeling during the course of treatment.
      Histologically, there were significant changes as a function of aging, i.e.,
      glomerular sclerosis with tubulointerstitial fibrosis in the kidney, and
      increased cardiomyocyte diameter with interstitial fibrosis in the heart at 48
      weeks. These changes were related to the enhanced inflammation and oxidative
      stress in the respective organs. However, there were no striking differences in
      BP among the groups, despite histological alterations in the EW group being
      significantly decreased when compared to FW and DW in both organs, with
      concurrently lower oxidative stress and inflammatory markers at 48 weeks.
      CONCLUSION: Long-term ad libitum consumption of H2-enriched electrolyzed water
      can ameliorate the processes of kidney injury and cardiac remodeling with aging
      in Dahl SS rats by suppressing, at least partly, elevated inflammation and
      oxidative stress.

PMID- 24289333
TI  - Opening a can of centipedes: new insights into mechanisms of body segmentation.
AB  - The search for a common developmental genetic mechanism of body segmentation
      appears to become more difficult, and more interesting, as new segmented
      organisms are added to the roster. Recent work in this journal by Brena and Akam
      on segmentation of the geophilomorph centipede Strigamia maritima, an arthropod
      distantly related to the standard insect models, contains developmental and
      evolutionary surprises that highlight the importance of a wider sampling of
      phyla.See research article: http://www.biomedcentral.com/1741-7007/11/112. 

PMID- 24289334
TI  - Communication: Thermodynamic analysis of critical conditions of polymer
      adsorption.
AB  - Polymer adsorption to solid surfaces is a ubiquitous phenomenon, which has
      attracted long-lasting attention. Dependent on the competition between the
      polymer-solid adsorption and polymer-solvent solvation interactions, a chain may
      assume either 3d solvated conformation when adsorption is weak or 2d adsorbed
      conformation when adsorption is strong. The transition between these
      conformations occurring upon variation of adsorption strength is quite sharp, and
      in the limit of "infinite" chain length, can be treated as a critical phenomenon.
      We suggest a novel thermodynamic definition of the critical conditions of polymer
      adsorption from the equality of incremental chemical potentials of adsorbed and
      free chains. We show with the example of freely jointed Lennard-Jones chains
      tethered to an adsorbing surface that this new definition provides a link between
      thermodynamic and geometrical features of adsorbed chains and is in line with
      classical scaling relationships for the fraction of adsorbed monomers, chain
      radii of gyration, and free energy. 

PMID- 24289335
TI  - Communication: Benzene dimer--the free energy landscape.
AB  - Establishing the relative orientation of the two benzene molecules in the dimer
      has remained an enigmatic challenge. Consensus has narrowed the choice of
      structures to either a T-shape, that may be tilted, or a parallel displaced
      arrangement, but the relatively small energy differences makes identifying the
      global minimum difficult. Here we report an ab initio Car-Parrinello Molecular
      Dynamics based metadynamics computation of the free-energy landscape of the
      benzene dimer. Our calculations show that although competing structures may be
      isoenergetic, free energy always favors a tilted T-shape geometry at all
      temperatures where the bound benzene dimer exist. 

PMID- 24289336
TI  - Communication: An accurate global potential energy surface for the ground
      electronic state of ozone.
AB  - We report a new full-dimensional and global potential energy surface (PES) for
      the O + O2 -> O3 ozone forming reaction based on explicitly correlated
      multireference configuration interaction (MRCI-F12) data. It extends our previous
      [R. Dawes, P. Lolur, J. Ma, and H. Guo, J. Chem. Phys. 135, 081102 (2011)]
      dynamically weighted multistate MRCI calculations of the asymptotic region which
      showed the widely found submerged reef along the minimum energy path to be the
      spurious result of an avoided crossing with an excited state. A spin-orbit
      correction was added and the PES tends asymptotically to the recently developed
      long-range electrostatic model of Lepers et al. [J. Chem. Phys. 137, 234305
      (2012)]. This PES features: (1) excellent equilibrium structural parameters, (2)
      good agreement with experimental vibrational levels, (3) accurate dissociation
      energy, and (4) most-notably, a transition region without a spurious reef. The
      new PES is expected to allow insight into the still unresolved issues surrounding
      the kinetics, dynamics, and isotope signature of ozone. 

PMID- 24289337
TI  - Communication: Enhanced oxygen reduction reaction and its underlying mechanism in
      Pd-Ir-Co trimetallic alloys.
AB  - Based on a combined density functional theory and experimental study, we present
      that the electrochemical activity of Pd3Co alloy catalysts toward oxygen
      reduction reaction (ORR) can be enhanced by adding a small amount of Ir. While Ir
      tends to favorably exist in the subsurface layers, the underlying Ir atoms are
      found to cause a substantial modification in the surface electronic structure. As
      a consequence, we find that the activation barriers of O/OH hydrogenation
      reactions are noticeably lowered, which would be mainly responsible for the
      enhanced ORR activity. Furthermore, our study suggests that the presence of Ir in
      the near-surface region can suppress Co out-diffusion from the Pd3Co substrate,
      thereby improving the durability of Pd-Ir-Co catalysts. We also discuss the
      relative roles played by Ir and Co in enhancing the ORR activity relative to
      monometallic Pd catalysts.

PMID- 24289338
TI  - Comparison between Gaussian-type orbitals and plane wave ab initio density
      functional theory modeling of layer silicates: talc [Mg3Si4O10(OH)2] as model
      system.
AB  - The quantum chemical characterization of solid state systems is conducted with
      many different approaches, among which the adoption of periodic boundary
      conditions to deal with three-dimensional infinite condensed systems. This
      method, coupled to the Density Functional Theory (DFT), has been proved
      successful in simulating a huge variety of solids. Only in relatively recent
      years this ab initio quantum-mechanic approach has been used for the
      investigation of layer silicate structures and minerals. In the present work, a
      systematic comparison of different DFT functionals (GGA-PBEsol and hybrid B3LYP)
      and basis sets (plane waves and all-electron Gaussian-type orbitals) on the
      geometry, energy, and phonon properties of a model layer silicate, talc
      [Mg3Si4O10(OH)2], is presented. Long range dispersion is taken into account by
      DFT+D method. Results are in agreement with experimental data reported in
      literature, with minimal deviation given by the GTO/B3LYP-D* method regarding
      both axial lattice parameters and interaction energy and by PW/PBE-D for the unit
      cell volume and angular values. All the considered methods adequately describe
      the experimental talc infrared spectrum.

PMID- 24289339
TI  - Multi-component symmetry-projected approach for molecular ground state
      correlations.
AB  - The symmetry-projected Hartree-Fock ansatz for the electronic structure problem
      can efficiently account for static correlation in molecules, yet it is often
      unable to describe dynamic correlation in a balanced manner. Here, we consider a
      multi-component, systematically improvable approach, that accounts for all ground
      state correlations. Our approach is based on linear combinations of symmetry
      projected configurations built out of a set of non-orthogonal, variationally
      optimized determinants. The resulting wavefunction preserves the symmetries of
      the original Hamiltonian even though it is written as a superposition of deformed
      (broken-symmetry) determinants. We show how short expansions of this kind can
      provide a very accurate description of the electronic structure of simple
      chemical systems such as the nitrogen and the water molecules, along the entire
      dissociation profile. In addition, we apply this multi-component symmetry
      projected approach to provide an accurate interconversion profile among the
      peroxo and bis(MU-oxo) forms of [Cu2O2](2+), comparable to other state-of-the-art
      quantum chemical methods. 

PMID- 24289340
TI  - Permutation invariant polynomial neural network approach to fitting potential
      energy surfaces. II. Four-atom systems.
AB  - A rigorous, general, and simple method to fit global and permutation invariant
      potential energy surfaces (PESs) using neural networks (NNs) is discussed. This
      so-called permutation invariant polynomial neural network (PIP-NN) method imposes
      permutation symmetry by using in its input a set of symmetry functions based on
      PIPs. For systems with more than three atoms, it is shown that the number of
      symmetry functions in the input vector needs to be larger than the number of
      internal coordinates in order to include both the primary and secondary invariant
      polynomials. This PIP-NN method is successfully demonstrated in three atom
      triatomic reactive systems, resulting in full-dimensional global PESs with
      average errors on the order of meV. These PESs are used in full-dimensional
      quantum dynamical calculations. 

PMID- 24289341
TI  - On the ground state calculation of a many-body system using a self-consistent
      basis and quasi-Monte Carlo: an application to water hexamer.
AB  - Given a quantum many-body system, the Self-Consistent Phonons (SCP) method
      provides an optimal harmonic approximation by minimizing the free energy. In
      particular, the SCP estimate for the vibrational ground state (zero temperature)
      appears to be surprisingly accurate. We explore the possibility of going beyond
      the SCP approximation by considering the system Hamiltonian evaluated in the
      harmonic eigenbasis of the SCP Hamiltonian. It appears that the SCP ground state
      is already uncoupled to all singly- and doubly-excited basis functions. So, in
      order to improve the SCP result at least triply-excited states must be included,
      which then reduces the error in the ground state estimate substantially. For a
      multidimensional system two numerical challenges arise, namely, evaluation of the
      potential energy matrix elements in the harmonic basis, and handling and
      diagonalizing the resulting Hamiltonian matrix, whose size grows rapidly with the
      dimensionality of the system. Using the example of water hexamer we demonstrate
      that such calculation is feasible, i.e., constructing and diagonalizing the
      Hamiltonian matrix in a triply-excited SCP basis, without any additional
      assumptions or approximations. Our results indicate particularly that the ground
      state energy differences between different isomers (e.g., cage and prism) of
      water hexamer are already quite accurate within the SCP approximation. 

PMID- 24289342
TI  - Charge asymmetry in rovibrationally excited HD+ determined using explicitly
      correlated all-particle Gaussian functions.
AB  - Very accurate non-Born-Oppenheimer quantum-mechanical calculations are performed
      to determine the average values of the interparticle distances and the proton
      deuteron density function for the rovibrationally excited HD(+) ion. The states
      corresponding to excitations to all bound vibrational states (v = 0, ..., 22) and
      simultaneously excited to the first excited rotational state (N = 1) are
      considered. To describe each state up to 8000 explicitly correlated all-particle
      Gaussian functions are used. The nonlinear parameters of the Gaussians are
      variationally optimized using a procedure that employs the analytical energy
      gradient determined with respect to these parameters. The results show an
      increasing asymmetry in the electron distribution with the vibrational excitation
      as the electron density shifts towards deuteron and away from the proton.

PMID- 24289343
TI  - Flexible nuclear screening approximation to the two-electron spin-orbit coupling
      based on ab initio parameterization.
AB  - The derivation, implementation, and validation of a new approximation to the two
      electron spin-orbit coupling (SOC) terms is reported. The approximation, referred
      to as flexible nuclear screening spin-orbit, is based on the effective one
      electron spin-orbit operator and accounts for two-electron SOC effects by
      screening nuclear charges. A highly flexible scheme for the nuclear screening is
      developed, mainly using parameterization based on ab initio atomic SOC
      calculations. Tabulated screening parameters are provided for contracted and
      primitive Gaussian-type basis functions of the ANO-RCC basis set for elements
      from H to Cm. The strategy for their adaptation to any other Gaussian basis set
      is presented and validated. A model to correct for the effect of splitting of
      transition metal d orbitals on their SOC matrix elements is introduced. The
      method is applied to a representative set of molecules, and compared to exact
      treatment and other approximative approaches at the same level of relativistic
      theory. The calculated SOC matrix elements are in very good agreement with their
      "exact" values; deviation below 1% is observed on average. The presented
      approximation is considered to be generally applicable, simple to implement,
      highly efficient, and accurate. 

PMID- 24289344
TI  - Automatic computer procedure for generating exact and analytical kinetic energy
      operators based on the polyspherical approach: general formulation and removal of
      singularities.
AB  - We present new techniques for an automatic computation of the kinetic energy
      operator in analytical form. These techniques are based on the use of the
      polyspherical approach and are extended to take into account Cartesian
      coordinates as well. An automatic procedure is developed where analytical
      expressions are obtained by symbolic calculations. This procedure is a full
      generalization of the one presented in Ndong et al., [J. Chem. Phys. 136, 034107
      (2012)]. The correctness of the new implementation is analyzed by comparison with
      results obtained from the TNUM program. We give several illustrations that could
      be useful for users of the code. In particular, we discuss some cyclic compounds
      which are important in photochemistry. Among others, we show that choosing a well
      adapted parameterization and decomposition into subsystems can allow one to avoid
      singularities in the kinetic energy operator. We also discuss a relation between
      polyspherical and Z-matrix coordinates: this comparison could be helpful for
      building an interface between the new code and a quantum chemistry package. 

PMID- 24289345
TI  - Origin of parameter degeneracy and molecular shape relationships in geometric
      flow calculations of solvation free energies.
AB  - Implicit solvent models are important tools for calculating solvation free
      energies for chemical and biophysical studies since they require fewer
      computational resources but can achieve accuracy comparable to that of explicit
      solvent models. In past papers, geometric flow-based solvation models have been
      established for solvation analysis of small and large compounds. In the present
      work, the use of realistic experiment-based parameter choices for the geometric
      flow models is studied. We find that the experimental parameters of solvent
      internal pressure p = 172 MPa and surface tension gamma = 72 mN/m produce
      solvation free energies within 1 RT of the global minimum root-mean-squared
      deviation from experimental data over the expanded set. Our results demonstrate
      that experimental values can be used for geometric flow solvent model parameters,
      thus eliminating the need for additional parameterization. We also examine the
      correlations between optimal values of p and gamma which are strongly anti
      correlated. Geometric analysis of the small molecule test set shows that these
      results are inter-connected with an approximately linear relationship between
      area and volume in the range of molecular sizes spanned by the data set. In spite
      of this considerable degeneracy between the surface tension and pressure terms in
      the model, both terms are important for the broader applicability of the model. 

PMID- 24289346
TI  - Stochastic thermodynamics of fluctuating density fields: non-equilibrium free
      energy differences under coarse-graining.
AB  - We discuss the stochastic thermodynamics of systems that are described by a time
      dependent density field, for example, simple liquids and colloidal suspensions.
      For a time-dependent change of external parameters, we show that the Jarzynski
      relation connecting work with the change of free energy holds if the time
      evolution of the density follows the Kawasaki-Dean equation. Specifically, we
      study the work distributions for the compression and expansion of a two
      dimensional colloidal model suspension implementing a practical coarse-graining
      scheme of the microscopic particle positions. We demonstrate that even if coarse
      grained dynamics and density functional do not match, the fluctuation relations
      for the work still hold albeit for a different, apparent, change of free energy. 

PMID- 24289347
TI  - Orbital-optimized density cumulant functional theory.
AB  - In density cumulant functional theory (DCFT) the electronic energy is evaluated
      from the one-particle density matrix and two-particle density cumulant,
      circumventing the computation of the wavefunction. To achieve this, the one
      particle density matrix is decomposed exactly into the mean-field (idempotent)
      and correlation components. While the latter can be entirely derived from the
      density cumulant, the former must be obtained by choosing a specific set of
      orbitals. In the original DCFT formulation [W. Kutzelnigg, J. Chem. Phys. 125,
      171101 (2006)] the orbitals were determined by diagonalizing the effective Fock
      operator, which introduces partial orbital relaxation. Here we present a new
      orbital-optimized formulation of DCFT where the energy is variationally minimized
      with respect to orbital rotations. This introduces important energy contributions
      and significantly improves the description of the dynamic correlation. In
      addition, it greatly simplifies the computation of analytic gradients, for which
      expressions are also presented. We offer a perturbative analysis of the new
      orbital stationarity conditions and benchmark their performance for a variety of
      chemical systems. 

PMID- 24289348
TI  - Hydrogen evolution from water through metal sulfide reactions.
AB  - Transition metal sulfides play an important catalytic role in many chemical
      reactions. In this work, we have conducted a careful computational study of the
      structures, electronic states, and reactivity of metal sulfide cluster anions
      M2S(X)(-) (M = Mo and W, X = 4-6) using density functional theory. Detailed
      structural analysis shows that these metal sulfide anions have ground state
      isomers with two bridging sulfide bonds, notably different in some cases from the
      corresponding oxides with the same stoichiometry. The chemical reactivity of
      these metal sulfide anions with water has also been carried out. After a thorough
      search on the reactive potential energy surface, we propose several competitive,
      energetically favorable, reaction pathways that lead to the evolution of
      hydrogen. Selectivity in the initial water addition and subsequent hydrogen
      migration are found to be the key steps in all the proposed reaction channels.
      Initial adsorption of water is most favored involving a terminal metal sulfur
      bond in Mo2S4(-) isomers whereas the most preferred orientation for water
      addition involves a bridging metal sulfur bond in the case of W2S4(-) and M2S5(-)
      isomers. In all the lowest energy H2 elimination steps, the interacting hydrogen
      atoms involve a metal hydride and a metal hydroxide (or thiol) group. We have
      also observed a higher energy reaction channel where the interacting hydrogen
      atoms in the H2 elimination step involve a thiol (-SH) and a hydroxyl (-OH)
      group. For all the reaction pathways, the Mo sulfide reactions involve a higher
      barrier than the corresponding W analogues. We observe for both metals that
      reactions of M2S4(-) and M2S5(-) clusters with water to liberate H2 are
      exothermic and involve modest free energy barriers. However, the reaction of
      water with M2S6(-) is highly endothermic with a considerable barrier due to
      saturation of the local bonding environment.

PMID- 24289349
TI  - Matrix isolation infrared spectroscopic and theoretical study of 1,1,1-trifluoro
      2-chloroethane (HCFC-133a).
AB  - The molecular structure and infrared spectrum of the atmospheric pollutant 1,1,1
      trifluoro-2-chloroethane (HCFC-133a; CF3CH2Cl) in the ground electronic state
      were characterized experimentally and theoretically. Excited state calculations
      (at the CASSCF, MR-CISD, and MR-CISD+Q levels) have also been performed in the
      range up to ~9.8 eV. The theoretical calculations show the existence of one
      (staggered) conformer, which has been identified spectroscopically for the
      monomeric compound isolated in cryogenic (~10 K) argon and xenon matrices. The
      observed infrared spectra of the matrix-isolated HCFC-133a were interpreted with
      the aid of MP2/aug-cc-pVTZ calculations and normal coordinate analysis, which
      allowed a detailed assignment of the observed spectra to be carried out,
      including identification of bands due to different isotopologues ((35)Cl and
      (37)Cl containing molecules). The calculated energies of the several excited
      states along with the values of oscillator strengths and previous results
      obtained for CFCs and HCFCs suggest that the previously reported photolyses of
      the title compound at 147 and 123.6 nm [T. Ichimura, A. W. Kirk, and E. Tschuikow
      Roux, J. Phys. Chem. 81, 1153 (1977)] are likely to be initiated in the n-4s and
      n-4p Rydberg states, respectively.

PMID- 24289350
TI  - Environmental effects on noble-gas hydrides: HXeBr, HXeCCH, and HXeH in noble-gas
      and molecular matrices.
AB  - Noble-gas hydrides HNgY (Ng is a noble-gas atom and Y is an electronegative
      group) are sensitive probes of local environment due to their relatively weak
      bonding and large dipole moments. We experimentally studied HXeBr in Ar, Kr, and
      N2 matrices, HXeCCH in Ne and N2 matrices, and HXeH in an N2 matrix. These are
      the first observations of noble-gas hydrides in an N2 matrix. An N2 matrix
      strongly increases the H-Xe stretching frequency of HXeBr and HXeCCH with respect
      to a Ne matrix, which is presumably due to a strong interaction between the HNgY
      dipole moment and quadrupole moments of the surrounding lattice N2 molecules. The
      spectral shift of HXeBr in an N2 matrix is similar to that in a CO2 matrix, which
      is a rather unexpected result because the quadrupole moment of CO2 is about three
      times as large as that of N2. The H-Xe stretching frequencies of HXeBr and HXeCCH
      in noble-gas matrices show a trend of nu(Ne) < nu(Xe) < nu(Kr) < nu(Ar), which is
      a non-monotonous function of the dielectric constants of the noble-gas solids.
      The MP2(full) calculations of HXeBr and HXeCCH with the polarizable continuum
      model as well as the CCSD(T) calculations of the HXeBr...Ng and HXeCCH...Ng (Ng =
      Ne, Ar, Kr, and Xe) complexes cannot fully explain the experimental observations.
      It is concluded that more sophisticated computational models should be used to
      describe these experimental findings.

PMID- 24289351
TI  - Rotational relaxation of CS by collision with ortho- and para-H2 molecules.
AB  - Quantum mechanical investigation of the rotationally inelastic collisions of CS
      with ortho- and para-H2 molecules is reported. The new global four-dimensional
      potential energy surface presented in our recent work is used. Close coupling
      scattering calculations are performed in the rigid rotor approximation for ortho-
      and para-H2 colliding with CS in the j = 0-15 rotational levels and for collision
      energies ranging from 10(-2) to 10(3) cm(-1). The cross sections and rate
      coefficients for selected rotational transitions of CS are compared with the ones
      previously reported for the collision of CS with He. The largest discrepancies
      are observed at low collision energy, below 1 cm(-1). Above 10 cm(-1), the
      approximation using the square root of the relative mass of the colliders to
      calculate the cross sections between a molecule and H2 from the data available
      with (4)He is found to be a good qualitative approximation. The rate coefficients
      calculated with the electron gas model for the He-CS system show more discrepancy
      with our accurate results. However, scaling up these rates by a factor of 2 gives
      a qualitative agreement. 

PMID- 24289352
TI  - A global ab initio potential energy surface for the X2A' ground state of the Si +
      OH -> SiO + H reaction.
AB  - We report the first global potential energy surface (PES) for the X(2)A' ground
      electronic state of the Si((3)P) + OH(X(2)Pi) -> SiO(X(1)Sigmag(+)) + H((2)S)
      reaction. The PES is based on a large number of ab initio energies obtained from
      multireference configuration interaction calculations plus Davidson correction
      (MRCI+Q) using basis sets of quadruple zeta quality. Corrections were applied to
      the ab initio energies in the reactant channel allowing a proper description of
      long-range interactions between Si((3)P) and OH(X(2)Pi). An analytical
      representation of the global PES has been developed by means of the reproducing
      kernel Hilbert space method. The reaction is found barrierless. Two minima,
      corresponding to the SiOH and HSiO isomers, and six saddle points, among which
      the isomerization transition state, have been characterized on the PES. The
      vibrational spectra of the SiOH/HSiO radicals have been computed from second
      order perturbation theory and quantum dynamics methods. The structural,
      energetic, and spectroscopic properties of the two isomers are in good agreement
      with experimental data and previous high quality calculations.

PMID- 24289353
TI  - Correlation between oxygen adsorption energy and electronic structure of
      transition metal macrocyclic complexes.
AB  - Oxygen adsorption energy is directly relevant to the catalytic activity of
      electrocatalysts for oxygen reduction reaction (ORR). In this study, we
      established the correlation between the O2 adsorption energy and the electronic
      structure of transition metal macrocyclic complexes which exhibit activity for
      ORR. To this end, we have predicted the molecular and electronic structures of a
      series of transition metal macrocyclic complexes with planar N4 chelation, as
      well as the molecular and electronic structures for the O2 adsorption on these
      macrocyclic molecules, using the density functional theory calculation method. We
      found that the calculated adsorption energy of O2 on the transition metal
      macrocyclic complexes was linearly related to the average position (relative to
      the lowest unoccupied molecular orbital of the macrocyclic complexes) of the non
      bonding d orbitals (d(z(2)), d(xy), d(xz), and d(yz)) which belong to the central
      transition metal atom. Importantly, our results suggest that varying the energy
      level of the non-bonding d orbitals through changing the central transition metal
      atom and/or peripheral ligand groups could be an effective way to tuning their O2
      adsorption energy for enhancing the ORR activity of transition metal macrocyclic
      complex catalysts.

PMID- 24289354
TI  - Electronic structural and magnetic properties of Mn5Ge3 clusters.
AB  - Theoretical understanding of the stability, ferromagnetism, and spin polarization
      of Mn5Ge3 clusters has been performed by using the density functional theory with
      generalized gradient approximation for exchange and correlation. The magnetic
      moments and magnetic anisotropy energy (MAE) have been calculated for both bulk
      and clusters, and the enhanced magnetic moment as well as the enlarged MAE have
      been identified in clusters. The most attractive achievement is that Mn5Ge3
      clusters show a fine half-metallic character with large energy scales. The
      present results may have important implications for potential applications of
      small Mn5Ge3 clusters as both emerging spintronics and next-generation data
      storage technologies. 

PMID- 24289355
TI  - Theoretical rotation-vibration spectrum of thioformaldehyde.
AB  - We present a variational calculation of the first comprehensive T = 300 K
      rovibrational line list for thioformaldehyde, H2CS. It covers 41,809
      rovibrational levels for states up to J(max) = 30 with vibrational band origins
      up to 5000 cm(-1) and provides the energies and line intensities for 547,926
      transitions from the ground vibrational state to these levels. It is based on our
      previously reported accurate ab initio potential energy surface and a newly
      calculated ab initio dipole moment surface. Minor empirical adjustments are made
      to the ab initio equilibrium geometry to reduce systematic errors in the
      predicted intra-band rotational energy levels. The rovibrational energy levels
      and transition intensities are computed variationally by using the methods
      implemented in the computer program TROVE. Transition wavelengths and intensities
      are found to be in excellent agreement with the available experimental data. The
      present calculations correctly reproduce the observed resonance effects, such as
      intensity borrowing, thus reflecting the high accuracy of the underlying ab
      initio surfaces. We report a detailed analysis of several vibrational bands,
      especially those complicated by strong Coriolis coupling, to facilitate future
      laboratory assignments.

PMID- 24289356
TI  - Low-energy positron scattering from gas-phase tetrahydrofuran: a quantum
      treatment of the dynamics and a comparison with experiments.
AB  - In this paper we report new quantum calculations of the dynamics for low-energy
      positrons interacting with gaseous molecules of tetrahydrofuran. The new quantum
      scattering cross sections are differential and integral cross sections at
      collision energies between 1.0 and 25.0 eV and include a careful treatment of the
      additional effects on the scattering process brought about by the permanent
      dipole moment of the target molecule. The present results are compared with an
      extensive range of measured data, both for the angular distributions and for the
      elastic integral cross sections and agree remarkably well with all findings. The
      new calculated quantities reported here also show the importance of correcting
      the experimental integral cross sections for the angular discrimination in the
      forward direction. 

PMID- 24289357
TI  - Photoabsorption spectrum of helium trimer cation--theoretical modeling.
AB  - The photoabsorption spectrum of He3(+) is calculated for two semiempirical models
      of intracluster interactions and compared with available experimental data
      reported in the middle UV range [H. Haberland and B. von Issendorff, J. Chem.
      Phys. 102, 8773 (1995)]. Nuclear delocalization effects are investigated via
      several approaches comprising quantum samplings using either exact or approximate
      (harmonic) nuclear wavefunctions, as well as classical samplings based on the
      Monte Carlo methodology. Good agreement with the experiment is achieved for the
      model by Knowles et al., [Mol. Phys. 85, 243 (1995); Mol. Phys. 87, 827 (1996)]
      whereas the model by Calvo et al., [J. Chem. Phys. 135, 124308 (2011)] exhibits
      non-negligible deviations from the experiment. Predictions of far UV absorption
      spectrum of He3(+), for which no experimental data are presently available, are
      reported for both models and compared to each other as well as to the
      photoabsorption spectrum of He2(+). A simple semiempirical point-charge
      approximation for calculating transition probabilities is shown to perform well
      for He3(+).

PMID- 24289358
TI  - Distributions of methyl group rotational barriers in polycrystalline organic
      solids.
AB  - We bring together solid state (1)H spin-lattice relaxation rate measurements,
      scanning electron microscopy, single crystal X-ray diffraction, and electronic
      structure calculations for two methyl substituted organic compounds to
      investigate methyl group (CH3) rotational dynamics in the solid state. Methyl
      group rotational barrier heights are computed using electronic structure
      calculations, both in isolated molecules and in molecular clusters mimicking a
      perfect single crystal environment. The calculations are performed on suitable
      clusters built from the X-ray diffraction studies. These calculations allow for
      an estimate of the intramolecular and the intermolecular contributions to the
      barrier heights. The (1)H relaxation measurements, on the other hand, are
      performed with polycrystalline samples which have been investigated with scanning
      electron microscopy. The (1)H relaxation measurements are best fitted with a
      distribution of activation energies for methyl group rotation and we propose,
      based on the scanning electron microscopy images, that this distribution arises
      from molecules near crystallite surfaces or near other crystal imperfections
      (vacancies, dislocations, etc.). An activation energy characterizing this
      distribution is compared with a barrier height determined from the electronic
      structure calculations and a consistent model for methyl group rotation is
      developed. The compounds are 1,6-dimethylphenanthrene and 1,8
      dimethylphenanthrene and the methyl group barriers being discussed and compared
      are in the 2-12 kJ mol(-1) range.

PMID- 24289360
TI  - Fragile to strong crossover at the Widom line in supercooled aqueous solutions of
      NaCl.
AB  - We study by molecular dynamics simulations the dynamical properties of an aqueous
      solution of NaCl at a concentration of 0.67 mol/kg upon supercooling. In a
      previous study of the same ionic solution, we have located the liquid-liquid
      critical point (LLCP) and determined the Widom line connected to the liquid
      liquid transition. We present here the results obtained from the study of the
      self-intermediate scattering function in a large range of temperatures and
      densities approaching the LLCP. The structural relaxation is in agreement with
      the mode coupling theory (MCT) in the region of mild supercooling. In the deeper
      supercooled region the alpha-relaxation time as function of temperature deviates
      from the MCT power law prediction showing a crossover from a fragile to a strong
      behavior. This crossover is found upon crossing the Widom line. The same trend
      was found in bulk water upon supercooling and it appears almost unchanged by the
      interaction with ions apart from a shift in the thermodynamic plane toward lower
      pressures and higher temperatures. These results show that the phenomenology of
      supercooled water transfers from bulk to solution where the study of the
      supercooled region is experimentally less difficult. 

PMID- 24289359
TI  - Mass and charge transport in 1-alkyl-3-methylimidazolium triflate ionic liquids.
AB  - Temperature-dependent transport properties in ionic liquids, such as the ionic
      conductivity and fluidity, are often characterized empirically through equations
      that require multiple adjustable fitting parameters in order to adequately
      describe the data. These fitting parameters offer no insight into the molecular
      level mechanism of transport. Here the temperature dependence of these transport
      properties in 1-alkyl-3-methylimidazolium triflate ionic liquids is explained
      using the compensated Arrhenius formalism (CAF), where the conductivity or
      fluidity assumes an Arrhenius-like form that also contains a dipole density
      dependence in the exponential prefactor. The resulting CAF activation energies
      for conductivity and fluidity are much higher than those obtained from polar
      organic liquids and electrolytes. The CAF very accurately describes the
      temperature dependence of both conductivity and fluidity using only system
      properties (i.e., density and activation energy). These results imply that the
      transport mechanism in molten salts is very similar to that in polar organic
      liquids and electrolytes. 

PMID- 24289361
TI  - Anomalous temperature dependence of the vibrational lifetime of the OD stretch
      vibration in ice and liquid water.
AB  - The temperature dependence of the vibrational T1 lifetime of the OD stretch
      vibration of HDO in H2O ice was measured with femtosecond mid-IR pump-probe
      spectroscopy. We found an increase of T1 from 480 +/- 40 fs at 25 K to 860 +/- 60
      fs at 265 K. These lifetimes are remarkably shorter than the vibrational lifetime
      of the OD stretch vibration of HDO in H2O in the liquid phase, which has a value
      of 1.7 +/- 0.1 ps at 274 K and increases to 2.24 +/- 0.09 at 343 K. The observed
      temperature dependence of T1 can be well explained from a relaxation mechanism in
      which the OD vibration relaxes via energy transfer to the bend-libration
      combination tones of H2O and HDO. 

PMID- 24289362
TI  - Instantaneous normal mode analysis for intermolecular and intramolecular
      vibrations of water from atomic point of view.
AB  - By exploiting the instantaneous normal mode (INM) analysis for models of flexible
      molecules, we investigate intermolecular and intramolecular vibrations of water
      from the atomic point of view. With two flexible SPC/E models, our investigations
      include three aspects about their INM spectra, which are separated into the
      unstable, intermolecular, bending, and stretching bands. First, the O- and H-atom
      contributions in the four INM bands are calculated and their stable INM spectra
      are compared with the power spectra of the atomic velocity autocorrelation
      functions. The unstable and intermolecular bands of the flexible models are also
      compared with those of the SPC/E model of rigid molecules. Second, we formulate
      the inverse participation ratio (IPR) of the INMs, respectively, for the O- and H
      atom and molecule. With the IPRs, the numbers of the three species participated
      in the INMs are estimated so that the localization characters of the INMs in each
      band are studied. Further, by the ratio of the IPR of the H atom to that of the O
      atom, we explore the number of involved OH bond per molecule participated in the
      INMs. Third, by classifying simulated molecules into subensembles according to
      the geometry of their local environments or their H-bond configurations, we
      examine the local-structure effects on the bending and stretching INM bands. All
      of our results are verified to be insensible to the definition of H-bond. Our
      conclusions about the intermolecular and intramolecular vibrations in water are
      given.

PMID- 24289363
TI  - Interfacial oxygen under TiO2 supported Au clusters revealed by a genetic
      algorithm search.
AB  - We present a density functional theory study of the oxidation of 1D periodic rods
      supported along the [001] direction on the rutile TiO2(110) surface. The study
      shows evidence for an oxidation of the interface between the supported Au and the
      TiO2 crystal. The added O atoms adsorb at the 5f-Ti atoms in the through under
      the Au rod and are stabilized by charge transfer from the nearest Au atoms.
      Despite an extensive search, we find no low energy barrier pathways for CO
      oxidation involving CO adsorbed on Au and O at the perimeter of the Au/TiO2
      interface. This is in part attributed the weak adsorption of CO on cationic Au at
      the perimeter. 

PMID- 24289364
TI  - Epitaxial growth of graphene on 6H-silicon carbide substrate by simulated
      annealing method.
AB  - We grew graphene epitaxially on 6H-SiC(0001) substrate by the simulated annealing
      method. The mechanisms that govern the growth process were investigated by
      testing two empirical potentials, namely, the widely used Tersoff potential [J.
      Tersoff, Phys. Rev. B 39, 5566 (1989)] and its more refined version published
      years later by Erhart and Albe [Phys. Rev. B 71, 035211 (2005)]. Upon contrasting
      the results obtained by these two potentials, we found that the potential
      proposed by Erhart and Albe is generally more physical and realistic, since the
      annealing temperature at which the graphene structure just coming into view at
      approximately 1200 K is unambiguously predicted and close to the experimentally
      observed pit formation at 1298 K within which the graphene nucleates. We
      evaluated the reasonableness of our layers of graphene by calculating carbon
      carbon (i) average bond-length, (ii) binding energy, and (iii) pair correlation
      function. Also, we compared with related experiments the various distance of
      separation parameters between the overlaid layers of graphene and substrate
      surface. 

PMID- 24289365
TI  - Long-range ordered nanodomains of grafted electroactive molecules.
AB  - We demonstrate the capability to build zero and one-dimensional electroactive
      molecular nanostructures ordered over a macroscopic scale and stable under
      ambient conditions. To realize these arrays, we use the selective grafting of
      functionalized thiols (juglon and terthiophene based) on a self-organized
      metallic template. The nanoscale patterning of the molecular conductance is
      demonstrated and analyzed by scanning tunneling spectroscopy. Finally, the
      influence of the nanostructuring on electro-chemical properties is measured,
      paving the way to an all-bottom-up fabrication of nanostructured templates for
      nanosciences. 

PMID- 24289366
TI  - Atomistic force field for alumina fit to density functional theory.
AB  - We present a force field for bulk alumina (Al2O3), which has been parametrized by
      fitting the energies, forces, and stresses of a large database of reference
      configurations to those calculated with density functional theory (DFT). We use a
      functional form that is simpler and computationally more efficient than some
      existing models of alumina parametrized by a similar technique. Nevertheless, we
      demonstrate an accuracy of our potential that is comparable to those existing
      models and to DFT. We present calculations of crystal structures and energies,
      elastic constants, phonon spectra, thermal expansion, and point defect formation
      energies. 

PMID- 24289367
TI  - Fluctuation theory of single-walled carbon nanotube formation.
AB  - In the framework of classical fluctuation theory an analytical formula is derived
      for the reversible work of formation of just detached carbon cap on the surface
      of catalyst nanoparticle (NP). This cap is considered as single walled carbon
      nanotube (SWCNT) formation center. The work of cap formation depends on the
      source carbon chemical potential MUC. Using the derived formula for this work an
      expression for the rate of SWCNT formation is determined. From this expression
      the SWCNT diameter distributions can be obtained. The obtained distributions have
      sharp maxima. It is found that the modal SWCNT diameter d(m) increases weakly
      with MUC being in the narrow window of 1.0 < d(m) < 1.8 nm when changing the
      source carbon chemical potential in a wide range. The determined diameter
      distributions proved to be in a good agreement with the typical values of the
      SWCNT diameters as experimentally measured in the chemical vapor deposition
      process. The increase of d(m) is accompanied by the increase of the distribution
      width Deltad. The selectivity d(m)/Deltad is a function of MUC, the higher values
      of MUC the worse selectivity is observed. Although the value of the SWCNT
      formation rate I cannot be calculated precisely the relationship between I and
      the system parameters, such as the NP radius R(S), can be obtained. This
      relationship is derived for the solid-liquid-solid system. To determine the
      function I(R(S)) for nanotubes of a certain diameter d, formulas for
      catalyst/amorphous carbon mutual solubilities as functions of NP radius are
      derived in the framework of the rigorous Gibbs theory of interface. Using the
      derived formulas an expression giving the dependence I(R(S)) is obtained. The
      expression predicts an increase of I with the radius R(S). The estimations
      carried out for the metal/carbon interface surface tension of 1000 mN/m show that
      the SWCNT formation rate increases by a few orders of magnitude with the radius
      increase from 1 to 10 nm.

PMID- 24289368
TI  - A hybrid kinetic Monte Carlo method for simulating silicon films grown by plasma
      enhanced chemical vapor deposition.
AB  - We present a powerful kinetic Monte Carlo (KMC) algorithm that allows one to
      simulate the growth of nanocrystalline silicon by plasma enhanced chemical vapor
      deposition (PECVD) for film thicknesses as large as several hundreds of
      monolayers. Our method combines a standard n-fold KMC algorithm with an efficient
      Markovian random walk scheme accounting for the surface diffusive processes of
      the species involved in PECVD. These processes are extremely fast compared to
      chemical reactions, thus in a brute application of the KMC method more than 99%
      of the computational time is spent in monitoring them. Our method decouples the
      treatment of these events from the rest of the reactions in a systematic way,
      thereby dramatically increasing the efficiency of the corresponding KMC
      algorithm. It is also making use of a very rich kinetic model which includes 5
      species (H, SiH3, SiH2, SiH, and Si2H5) that participate in 29 reactions. We have
      applied the new method in simulations of silicon growth under several conditions
      (in particular, silane fraction in the gas mixture), including those usually
      realized in actual PECVD technologies. This has allowed us to directly compare
      against available experimental data for the growth rate, the mesoscale
      morphology, and the chemical composition of the deposited film as a function of
      dilution ratio. 

PMID- 24289369
TI  - Strain-induced orbital polarization and multiple phase transitions in Ba2MnWO6
      from first principles.
AB  - Electronic structures of double perovskite Ba2MnWO6 with epitaxial strain are
      explored by using methods based on density functional theory. An in-plane
      compressive strain is found not only resulting in a semiconductor-metal
      transition (SMT), but also altering the magnetic structures, from different kinds
      of antiferromagnetic to ferromagnetic orders. Orbital polarization and different
      orbital occupancies of Mn d(z(2)) and d(x(2)-y(2)) states, induced by the
      epitaxial strain, are employed to understand the SMT. The rich magnetic phase
      transitions are rationalized by a magnetic stabilization mechanism. Our results
      show that many technological applications may be carried out in the material with
      the control of epitaxial strain.

PMID- 24289370
TI  - Capacitance enhancement via electrode patterning.
AB  - The necessity of increasing the energy density in electric double layer
      capacitors to meet current demand is fueling fundamental and applied research
      alike. We report here molecular dynamics simulation results for aqueous
      electrolytes near model electrodes. Particular focus is on the effect of
      electrode patterning on the structure of interfacial electrolytes, and on the
      potential drop between the solid electrodes and the bulk electrolytes. The latter
      is estimated by numerically integrating the Poisson equation using the charge
      densities due to water and ions accumulated near the interface as input. We
      considered uniform and patterned electrodes, both positively and negatively
      charged. The uniformly charged electrodes are modeled as graphite. The patterned
      ones are obtained by removing carbon atoms from the top-most graphene layer,
      yielding nanoscopic squares and stripes patterns. For simplicity, the patterned
      electrodes are effectively simulated as insulators (the charge remains localized
      on the top-most layer of carbon atoms). Our simulations show that the patterns
      alter the structure of water and the accumulation of ions at the liquid-solid
      interfaces. Using aqueous NaCl solutions, we found that while the capacitance
      calculated for three positively charged electrodes did not change much, that
      calculated for the negatively charged electrodes significantly increased upon
      patterning. We find that both water structure and orientation, as well as ion
      accumulation affect the capacitance. As electrode patterning affects differently
      water structure and ion accumulation, it might be possible to observe ion
      specific effects. These results could be useful for advancing our understanding
      of electric double layer capacitors, capacitive desalination processes, as well
      as of fundamental interfacial electrolytes properties. 

PMID- 24289371
TI  - Van der Waals density functional study of the structural and electronic
      properties of La-doped phenanthrene.
AB  - By the first principle calculations based on the van der Waals density functional
      theory, we study the crystal structures and electronic properties of La-doped
      phenanthrene. Two stable atomic geometries of La1phenanthrene are obtained by
      relaxation of atomic positions from various initial structures. The structure-I
      is a metal with two energy bands crossing the Fermi level, while the structure-II
      displays a semiconducting state with an energy gap of 0.15 eV, which has an
      energy gain of 0.42 eV per unit cell compared to the structure-I. The most
      striking feature of La1phenanthrene is that La 5d electrons make a significant
      contribution to the total density of state around the Fermi level, which is
      distinct from potassium doped phenanthrene and picene. Our findings provide an
      important foundation for the understanding of superconductivity in La-doped
      phenanthrene.

PMID- 24289372
TI  - Formation of ordered films of axially bridged aluminum phthalocyanine
      [(tBu)4PcAl]2O via magnetic field-induced reaction.
AB  - The MU-(oxo)bis[tetra-tert-butylphthalocyaninato] aluminum(III) [(tBu)4PcAl]2O
      films with the crystallites oriented preferably in one direction were obtained
      via chemical transformation of tetra-tert-butylsubstituted chloroaluminum(III)
      phthalocyanine (tBu)4PcAlCl film upon its annealing in magnetic field. A
      comparative analysis of the influence of post-deposition annealing process
      without and under applied magnetic field of 1 T, on the orientation and
      morphology of (tBu)4PcAlCl and [(tBu)4PcAl]2O films, has been carried out by the
      methods of UV-vis, Infrared and Raman spectroscopies, XRD as well as atomic force
      microscopy. The formation of [(tBu)4PcAl]2O films with elongated crystallites
      having preferential orientation was observed upon heating of the films in
      magnetic field while annealing without magnetic field under the same conditions
      does not demonstrate any effect on the structure and morphology of these films.
      The reasons of the sensitivity of this reaction to the presence of such magnetic
      field is discussed and studied by electronic paramagnetic resonance spectroscopy.

PMID- 24289373
TI  - Polarization of positronium in amorphous polar polymers: a case study.
AB  - The features of positronium in an amorphous copolymer (polyvinyl acetate-crotonic
      acid) in a range of temperatures including the glass transition were investigated
      by means of positron annihilation lifetime spectroscopy. In particular, para
      positronium lifetime was found to be longer than in a vacuum and to decrease with
      the temperature. This was attributed to the electron density at the positron
      (contact density), which is lower than in vacuo due to the presence of polar
      groups in the copolymer. A three quantum yield experiment confirmed the lifetime
      results. 

PMID- 24289374
TI  - A picture of dilute solution behavior of polymers through polyelectrolyte
      simulation.
AB  - A Monte Carlo (MC) study is made of the persistence length q and the binary
      cluster integral beta (or the excluded-volume strength B) for polyelectrolytes by
      the use of the discrete Kratky-Porod wormlike chain with hard-core-effective
      Debye-Huckel electrostatic pair potentials. The quantity q is determined from the
      initial decay rate of the bond correlation function after preliminary
      confirmation of the validity of this procedure using the chain with Lennard-Jones
      pair potentials. The quantity B is determined from the mean-square radius of
      gyration along with q by the use of the quasi-two-parameter (QTP) excluded-volume
      theory. They are evaluated for two model cases of polyelectrolytes, sodium
      hyaluronate as an example of semiflexible polymers and poly(sodium 4
      styrenesulfonate) as a typical example of flexible polymers, both in aqueous
      sodium chloride. The behavior of MC data so obtained for q and B as functions of
      added salt concentration c is examined in detail, comparing them with the Odijk
      Skolnick-Fixman theory of q and the Fixman-Skolnick (FS) theory of B and also
      with literature experimental data. In particular, the MC values of B are in
      almost complete agreement with the FS theory for large c, although the latter
      still overestimates B somewhat for small c. The values of B themselves and also
      the validity of the QTP theory in general are discussed in comparison with the
      case of nonionic polymers.

PMID- 24289375
TI  - Cross-over between central and non-central conservative effective forces in a
      modulated colloidal fluid.
AB  - We study by Monte Carlo simulations the effective forces between two particles
      dispersed in a two-dimensional colloidal fluid, modulated in one direction by a
      spatially periodic external potential. When the modulation strength exceeds the
      strength of interaction between the dispersed and dispersing particles, the
      anisotropic effective forces, show cross-over between central and non-central
      nature, although the effective forces remain conservative. The non-central nature
      of the effective forces depends on the orientation of the separation vector
      between the dispersed particles with respect to the modulation direction. 

PMID- 24289376
TI  - Simulation study on the structure of rod-coil-rod triblock copolymer and
      nanoparticle mixture within slit.
AB  - Self-assembly structures of rod-coil-rod ABA triblock copolymer and nanoparticle
      mixture within a slit are simulated by dissipative particle dynamics method.
      Results show that the structures are dependent on the rigidity of the rod block
      ktheta, the interaction between the rod block and slit a(wA), the fraction of rod
      block f(A), and the slit height H. With an increase in ktheta, we observe a
      transition from parallel lamellae to hexagonal cylinders. While with the increase
      in a(wA), the parallel lamellae at small ktheta and hexagonal cylinders at large
      ktheta change to perpendicular lamellae at large a(wA) close to a(As). At last,
      we present a phase diagram of structure with respect to f(A) and H at large
      ktheta.

PMID- 24289377
TI  - Cluster-continuum quantum mechanical models to guide the choice of anions for
      Li(+)-conducting ionomers.
AB  - A quantum-mechanical investigation on Li poly(ethylene oxide)-based ionomers was
      performed in the cluster-continuum solvation model (CCM) that includes specific
      solvation in the first shell surrounding the cation, all surrounded by a
      polarizable continuum. A four-state model, including a free Li cation, Li(+)
      anion pair, triple ion, and quadrupole was used to represent the states of Li(+)
      within the ionomer in the CCM. The relative energy of each state was calculated
      for Li(+) with various anions, with dimethyl ether representing the ether oxygen
      solvation. The population distribution of Li(+) ions among states was estimated
      by applying Boltzmann statistics to the CCM energies. Entropy difference
      estimates are needed for populations to better match the true ionomer system. The
      total entropy change is considered to consist of four contributions:
      translational, rotational, electrostatic, and solvent immobilization entropies.
      The population of ion states is reported as a function of Bjerrum length divided
      by ion-pair separation with/without entropy considered to investigate the
      transition between states. Predicted concentrations of Li(+)-conducting states
      (free Li(+) and positive triple ions) are compared among a series of anions to
      indicate favorable features for design of an optimal Li(+)-conducting ionomer;
      the perfluorotetraphenylborate anion maximizes the conducting positive triple ion
      population among the series of anions considered.

PMID- 24289378
TI  - Calorimetric study of phase transitions in ocylcyanobiphenyl-barium titanate
      nanoparticle dispersions.
AB  - High-resolution ac-calorimetry is reported on the weakly first-order isotropic to
      nematic (I-N) and the continuous nematic to smectic-A (N-SmA) phase transitions
      in the liquid crystal octylcyanobiphenyl (8CB) doped with a ferroelectric
      nanoparticle barium titanate, BaTiO3 (BT). Measurements were performed as a
      function of BT concentration and over a wide temperature range well above and
      below the two transitions. From the thermal scans of all samples (having BT mass
      fraction phi(m) = 0.001 to 0.014 and pure 8CB), both the I-N and the N-SmA
      transitions evolve in character. Specifically, there appears an unusual change of
      the I-N specific heat peak shape on heating as phi(m) increases. Both the
      transitions shift to lower temperature at a different rate for
      phi(m)<phi(m)(c)=0.002 as compared to that for phi(m)>phi(m)(c). The effective
      transition enthalpies are essentially constant and similar to that seen in the
      bulk. Using a simple geometric model, the mean distance between the BT particles
      at the cross-over phi(m)(c) is found to be x(c)~3 MUm, which is consistent with
      an estimated surface extrapolation length b for the nematic director. This
      suggests that the low phi(m) regime is dominated by an impurity/disorder effect
      while for phi(m)>phi(m)(c) the mean distance is small enough for the LC to
      mediate coupling between the BT ferroelectric nanoparticles.

PMID- 24289379
TI  - Human aquaporin 4 gating dynamics under and after nanosecond-scale static and
      alternating electric-field impulses: a molecular dynamics study of field effects
      and relaxation.
AB  - Water self-diffusion and the dipolar response of the selectivity filter within
      human aquaporin 4 have been studied using molecular dynamics (MD) simulations in
      the absence and presence of pulses of external static and alternating electric
      fields. The pulses were approximately 50 and 100 ns in duration and 0.0065 V/A in
      (r.m.s.) intensity and were either static or else 2.45 or 100 GHz in frequency
      and applied both along and perpendicular to the channels. In addition, the
      relaxation of the aquaporin, water self-diffusion and gating dynamics following
      cessation of the impulses was studied. In previous work it was determined that
      switches in the dihedral angle of the selectivity filter led to boosting of water
      permeation events within the channels, in the presence of identical external
      static and alternating electric fields, although applied continuously. Here the
      application of field impulses (and subsequently, upon removal) has shown that it
      is the dipolar orientation of the histidine-201 residue in the selectivity filter
      which governs the dihedral angle, and hence influences water self-diffusion; this
      constitutes an appropriate order parameter. The dipolar response of this residue
      to the applied field leads to the adoption of four distinct states, which we
      modelled as time-homogeneous Markov jump processes, and may be distinguished in
      the potential of mean force (PMF) as a function of the dipolar orientation of
      histidine-201. The observations of enhanced "dipolar flipping" of H201 serve to
      explain increased levels of water self-diffusion within aquaporin channels
      during, and immediately following, field impulses, although the level of
      statistical certainty here is lower. Given the appreciable size of the energy
      barriers evident in PMFs computed directly from deterministic MD (whether in the
      absence or presence of external fields), metadynamics calculations were
      undertaken to explore the free-energy landscape of histidine-201 orientation with
      greater accuracy and precision. These indicate that electric fields do alter the
      free-energy profile of the H201 side-chain orientation, wherein a perturbation of
      the symmetric bimodal state evident in the zero-field case is observed. These
      effects are dependent on the field intensities.

PMID- 24289380
TI  - On the physics of multidrug efflux through a biomolecular complex.
AB  - Insertion and release of a solute into and from a vessel comprising biopolymers
      is a fundamental function in a biological system. A typical example is found in a
      multidrug efflux transporter. "Multidrug efflux" signifies that solutes such as
      drug molecules with diverse properties can be handled. In our view, the mechanism
      of the multidrug efflux is not chemically specific but rather has to be based on
      a physical factor. In earlier works, we showed that the spatial distribution of
      the solute-vessel potential of mean force (PMF) induced by the solvent plays
      imperative roles in the insertion/release process. The PMF can be decomposed into
      the energetic and entropic components. The entropic component, which originates
      from the translational displacement of solvent molecules, is rather insensitive
      to the solute-solvent and vessel inner surface-solvent affinities. This feature
      is not shared with the energetic component. When the vessel inner surface is
      neither solvophobic nor solvophilic, the solvents within the vessel cavity and in
      the bulk offer almost the same environment to any solute with solvophobicity or
      solvophilicity, and the energetic component becomes much smaller than the
      entropic component (i.e., the latter predominates over the former). Our idea is
      that the multidrug efflux can be realized if the insertion/release process is
      accomplished by the entropic component exhibiting the insensitivity to the solute
      properties. However, we have recently argued that the entropic release of the
      solute is not feasible as long as the vessel geometry is fixed. Here we consider
      a model of TolC, a cylindrical vessel possessing an entrance at one end and an
      exit at the other end for the solute. The spatial distribution of the PMF is
      calculated by employing the three-dimensional integral equation theory with rigid
      body models in which the constituents interact only through hard-body potentials.
      Since the behavior of these models is purely entropic in origin, our analysis is
      focused on the entropic component. We show that the entropically inserted solute
      can be released by a continuous variation of the vessel geometry which forms a
      time-dependent entropic force continuing to accelerate the solute motion to the
      exit. Solutes with a wide range of sizes are entropically released using the same
      vessel-geometry variation. The results obtained are fairly general and also
      applicable to the efflux pump protein AcrB and ATP-binding cassette transporter.

PMID- 24289383
TI  - New multiplexed all solid state pulser for high power wide aperture kinetically
      enhanced copper vapor laser.
AB  - A novel multiplexed scheme is demonstrated to combine two or more pulsed solid
      state pulsers of moderate capabilities. Pulse power supply comprising of two
      solid state pulsers of ~6 kW rating each in multiplexed mode with common magnetic
      pulse compression stage was demonstrated and optimized for operating with a wide
      aperture kinetically enhanced copper vapor laser. Using this new configuration,
      the multiplexed pulsed power supply was capable of operating efficiently at net
      repetition-rate of ~13 kHz, 12 kW (wall plug average power), 18-20 kV discharge
      voltage and pulse rise-time of ~80 ns. The laser under multiplexed configuration
      delivered un-interrupted output power of about ~80 W with scope of further
      increase in laser output power in excess of 100 W.

PMID- 24289382
TI  - Off-resonance energy absorption in a linear Paul trap due to mass selective
      resonant quenching.
AB  - Linear Paul traps (LPT) are used in many experimental studies such as mass
      spectrometry, atom-ion collisions, and ion-molecule reactions. Mass selective
      resonant quenching (MSRQ) is implemented in LPT either to identify a charged
      particle's mass or to remove unwanted ions from a controlled experimental
      environment. In the latter case, MSRQ can introduce undesired heating to co
      trapped ions of different mass, whose secular motion is off resonance with the
      quenching ac field, which we call off-resonance energy absorption (OREA). We
      present simulations and experimental evidence that show that the OREA increases
      exponentially with the number of ions loaded into the trap and with the amplitude
      of the off-resonance external ac field. 

PMID- 24289381
TI  - Invited review article: Methods for imaging weak-phase objects in electron
      microscopy.
AB  - Contrast has traditionally been produced in electron-microscopy of weak phase
      objects by simply defocusing the objective lens. There now is renewed interest,
      however, in using devices that apply a uniform quarter-wave phase shift to the
      scattered electrons relative to the unscattered beam, or that generate in-focus
      image contrast in some other way. Renewed activity in making an electron-optical
      equivalent of the familiar "phase-contrast" light microscope is based in part on
      the improved possibilities that are now available for device microfabrication.
      There is also a better understanding that it is important to take full advantage
      of contrast that can be had at low spatial frequency when imaging large,
      macromolecular objects. In addition, a number of conceptually new phase-plate
      designs have been proposed, thus increasing the number of options that are
      available for development. The advantages, disadvantages, and current status of
      each of these options is now compared and contrasted. Experimental results that
      are, indeed, superior to what can be accomplished with defocus-based phase
      contrast have been obtained recently with two different designs of phase-contrast
      aperture. Nevertheless, extensive work also has shown that fabrication of such
      devices is inconsistent, and that their working lifetime is short. The main
      limitation, in fact, appears to be electrostatic charging of any device that is
      placed into the electron diffraction pattern. The challenge in fabricating phase
      plates that are practical to use for routine work in electron microscopy thus may
      be more in the area of materials science than in the area of electron optics. 

PMID- 24289384
TI  - Optical-fiber frequency domain interferometer with nanometer resolution and
      centimeter measuring range.
AB  - A new optical-fiber frequency domain interferometer (OFDI) device for accurate
      measurement of the absolute distance between two stationary objects, with
      centimeter measuring range and nanometer resolution, has been developed. Its
      working principle and on-line data processing method were elaborated. The new
      OFDI instrument was constructed all with currently available commercial
      communication products. It adopted the wide-spectrum amplified spontaneous
      emission light as the light source and optical-fiber tip as the test probe. Since
      this device consists of only fibers or fiber coupled components, it is very
      compact, convenient to operate, and easy to carry. By measuring the single-step
      length of a translation stage and the thickness of standard gauge blocks, its
      ability in implementing nanometer resolution and centimeter measuring range on
      line measurements was validated. 

PMID- 24289385
TI  - Supercontinuum spatial modulation spectroscopy: detection and noise limitations.
AB  - Supercontinuum spatial modulation spectroscopy is a facile tool for conducting
      single molecule/particle extinction spectroscopy throughout the visible and near
      infrared (420-1100 nm). The technique's capabilities are benchmarked using
      individual Au nanoparticles (NPs) as a standard since they are well studied and
      display a prominent plasmon resonance in the visible. Extinction spectra of
      individual Au NPs with diameters (d) ranging from d ~ 8 to 40 nm are resolved
      with extinction cross sections (sigma(ext)) of sigma(ext) ~ 1 * 10(-13)-1 * 10(
      11) cm(2). Corresponding signal-to-noise ratios range from ~30 to ~1400. The
      technique's limit of detection is determined to be 4.3 * 10(-14) cm(2) (4.3
      nm(2)). To showcase supercontinuum spatial modulation spectroscopy's broader
      applicability, extinction spectra are acquired for other model systems, such as
      individual single-walled carbon nanotubes (SWCNTs) and CdSe nanowires. We show
      for the first time extinction spectra of individual (8,3) and (6,5) SWCNTs. For
      both chiralities, their E11 [(8,3) 1.30 eV (952 nm); (6,5) 1.26 eV (986 nm)] and
      E22 [(8,3) 1.86 eV (667 nm); (6,5) 2.19 eV (567 nm)] excitonic resonances are
      seen with corresponding cross sections of sigma(ext) ~ 10(-13) cm(2) MUm(-1).

PMID- 24289386
TI  - A multi purpose source chamber at the PLEIADES beamline at SOLEIL for
      spectroscopic studies of isolated species: cold molecules, clusters, and
      nanoparticles.
AB  - This paper describes the philosophy and design goals regarding the construction
      of a versatile sample environment: a source capable of producing beams of atoms,
      molecules, clusters, and nanoparticles in view of studying their interaction with
      short wavelength (vacuum ultraviolet and x-ray) synchrotron radiation. In the
      design, specific care has been taken of (a) the use standard components, (b)
      ensuring modularity, i.e., that swiftly switching between different experimental
      configurations was possible. To demonstrate the efficiency of the design, proof
      of-principle experiments have been conducted by recording x-ray absorption and
      photoelectron spectra from isolated nanoparticles (SiO2) and free mixed clusters
      (Ar/Xe). The results from those experiments are showcased and briefly discussed. 

PMID- 24289387
TI  - New method for measuring time-resolved spectra of lanthanide emission using
      square-wave excitation.
AB  - A method using modulated continuous wave (CW) visible laser to measure time
      resolved fluorescence spectra of trivalent rare-earth ions has been developed.
      Electro-optic modulator was used to modulate the CW pumping laser with a rise
      time of 2 MUs. CW Nd(3+) lasers were used as examples to present the method.
      Upconversion dynamic process of Ho(3+) was studied utilizing a 532 nm CW laser.
      Quantum cutting dynamic process from Tb(3+) to Yb(3+) was analyzed by a 473 nm CW
      laser. This method can be applied to any CW laser such as He-Ne laser, Ar(+)
      laser, Kr(+) laser, Ti:sapphire laser, etc. 

PMID- 24289388
TI  - Reaction cell for in situ soft x-ray absorption spectroscopy and resonant
      inelastic x-ray scattering measurements of heterogeneous catalysis up to 1 atm
      and 250  degrees C.
AB  - We present a novel in situ reaction cell for heterogeneous catalysis monitored in
      situ by x-ray absorption spectroscopy (XAS) and resonant inelastic x-ray
      scattering (RIXS). The reaction can be carried out at a total pressure up to 1
      atm, a regime that has not been accessible to comparable in situ techniques and
      thus closes the pressure gap to many industrial standard conditions. Two
      alternate catalyst geometries were tested: (A) a thin film evaporated directly
      onto an x-ray transparent membrane with a flowing reaction gas mixture behind it
      or (B) a powder placed behind both the membrane and a gap of flowing reaction gas
      mixture. To illustrate the working principle and feasibility of our reaction cell
      setup we have chosen ethylene epoxidation over a silver catalyst as a test case.
      The evolution of incorporated oxygen species was monitored by total
      electron/fluorescence yield O K-XAS as well as O K-RIXS, which is a powerful
      method to separate contributions from inequivalent sites. We find that our method
      can reliably detect transient species that exist during catalytic reaction
      conditions that are hardly accessible using other spectroscopic methods. 

PMID- 24289389
TI  - Depth-resolved confocal micro-Raman spectroscopy for characterizing GaN-based
      light emitting diode structures.
AB  - In this work, we demonstrate that depth-resolved confocal micro-Raman
      spectroscopy can be used to characterize the active layer of GaN-based LEDs. By
      taking the depth compression effect due to refraction index mismatch into
      account, the axial profiles of Raman peak intensities from the GaN capping layer
      toward the sapphire substrate can correctly match the LED structural dimension
      and allow the identification of unique Raman feature originated from the 0.3 MUm
      thick active layer of the studied LED. The strain variation in different sample
      depths can also be quantified by measuring the Raman shift of GaN A1(LO) and
      E2(high) phonon peaks. The capability of identifying the phonon structure of
      buried LED active layer and depth-resolving the strain distribution of LED
      structure makes this technique a potential optical and remote tool for in
      operando investigation of the electronic and structural properties of nitride
      based LEDs. 

PMID- 24289390
TI  - Production of energetic neutral particles and low energy electrons from four
      anode rods ion source.
AB  - The factors affecting the energetic neutral current, the low energy electron
      current, and the positive ion current emerging from a four-anode-rods ion source
      have been studied using argon gas. The neutral and electron current were measured
      using a simple, new technique. It was found that the energetic neutral current
      and the electron current depend on the positive ion current and the gas pressure.
      The ratio of the neutral and electron current to the positive ion current
      increases by increasing the gas pressure. Also it was found that at a pressure
      equal to 9 * 10(-4) mmHg, the ratio of the neutral to the positive ion current
      reaches 2.34 while the ratio of the electron current to the positive ion current
      reaches 1.7. 

PMID- 24289391
TI  - Compton scattering for spectroscopic detection of ultra-fast, high flux, broad
      energy range X-rays.
AB  - Compton side-scattering has been used to simultaneously downshift the energy of
      keV to MeV energy range photons while attenuating their flux to enable single
      shot, spectrally resolved, measurements of high flux X-ray sources to be
      undertaken. To demonstrate the technique a 1 mm thick pixelated cadmium telluride
      detector has been used to measure spectra of Compton side-scattered radiation
      from a Cobalt-60 laboratory source and a high flux, high peak brilliance X-ray
      source of betatron radiation from a laser-plasma wakefield accelerator. 

PMID- 24289392
TI  - Precision phase control for the radio frequency system of K500 superconducting
      cyclotron at Variable Energy Cyclotron Centre, Kolkata.
AB  - Variable Energy Cyclotron Centre (VECC) has commissioned K500 Superconducting
      cyclotron (SCC) based on MSU and Texas A&M university cyclotrons. The radio
      frequency (RF) system of SCC has been commissioned with the stringent requirement
      of various RF parameters. The three-phase RF system of Superconducting cyclotron
      has been developed in the frequency range 9-27 MHz with amplitude and phase
      stability of 100 ppm and +/-0.1 degrees , respectively. The phase control system
      has the option to change the relative phase difference between any two RF
      cavities and maintain the phase stability within +/-0.1 degrees  during round-the
      clock cyclotron operation. The said precision phase loop consists of both
      analogue In-phase/Quadrature modulator to achieve faster response and also Direct
      Digital Synthesis based phase shifter to achieve wide dynamic range as well. This
      paper discusses detail insights into the various issues of phase control for the
      K500 SCC at VECC, Kolkata. 

PMID- 24289393
TI  - The external Q factor of a dual-feed coupling for superconducting radio frequency
      cavities: theoretical and experimental studies.
AB  - We propose a theoretical model based on network analysis to study the external
      quality factor (Q factor) of dual-feed coupling for superconducting radio
      frequency (SRF) cavities. Specifically, we apply our model to the dual-feed 704
      MHz half-cell SRF gun for Brookhaven National Laboratory's prototype Energy
      Recovery Linac (ERL). The calculations show that the external Q factor of this
      dual-feed system is adjustable from 10(4) to 10(9) provided that the adjustment
      range of a phase shifter covers 0 degrees -360 degrees . With a period of 360
      degrees , the external Q factor of the coupling system changes periodically with
      the phase difference between the two coupling arms. When the RF phase of both
      coupling arms is adjusted simultaneously in the same direction, the external Q
      factor of the system also changes periodically, but with a period of 180 degrees
      . 

PMID- 24289394
TI  - A real-time intercepting beam-profile monitor for a medical cyclotron.
AB  - There is a lack of real-time continuous beam-diagnostic tools for medical
      cyclotrons due to high power deposition during proton irradiation. To overcome
      this limitation, we have developed a profile monitor that is capable of providing
      continuous feedback about beam shape and current in real time while it is
      inserted in the beam path. This enables users to optimize the beam profile and
      observe fluctuations in the beam over time with periodic insertion of the
      monitor. 

PMID- 24289396
TI  - An initial measurement of a fast neutral spectrum for ion cyclotron range of
      frequency heated plasma using two-channel compact neutral particle analyzers in
      KSTAR.
AB  - The accurate measurement of fast neutral particles from high energy ion tails is
      very important since it is a measure of ion cyclotron range of frequency (ICRF)
      or neutral beam (NB) ion heating. In KSTAR, fast neutral measurements have been
      carried out using a compact neutral particle analyzer based on the silicon photo
      diode since 2010. As a result, the fast neutral spectrum was observed consistent
      with the ion temperature, diamagnetic energy, and neutron flux in 2011. However,
      there was fast neutral count beyond the injected neutral beam energy in NB-only
      heating. Since it is difficult to expect the count unless the temperature is high
      enough to diffuse the fast ions beyond the beam energy it was required to
      identify what it is. During the 2012 campaign, the two-channel diode detectors
      with and without a particle stopper were used to distinguish fast neutral counts
      and other counts by a hard X-ray or neutrons. As a result, it was confirmed that
      the high energy component beyond the beam energy originated from a hard X-ray or
      neutrons. Finally, it was observed that faster neutrals are generated by ICRF
      heating and enhanced by electron cyclotron heating compared to NB-only heating. 

PMID- 24289395
TI  - Development of electron cyclotron emission imaging system on the HL-2A tokamak.
AB  - A 2D electron cyclotron emission imaging (ECEI) system has been developed for
      measurement of electron temperature fluctuations in the HL-2A tokamak. It is
      comprised of a front-end 24 channel heterodyne imaging array with a tunable RF
      range spanning 75-110 GHz, and a set of back-end ECEI electronics that together
      generate 24 * 8 = 192 channel images of the 2nd harmonic X-mode electron
      cyclotron emission from the HL-2A plasma. The simulated performance of the local
      oscillator (LO) optics and radio frequency (RF) optics is presented, together
      with the laboratory characterization results. The Gaussian beams from the LO
      optics are observed to properly cover the entire detector array. The ECE signals
      from the plasma are mixed with the LO signal in the array box, then delivered to
      the electronics system by low-loss microwave cables, and finally to the
      digitizers. The ECEI system can achieve temporal resolutions of ~MUs, and spatial
      resolutions of 1 cm (radially) and 2 cm (poloidally).

PMID- 24289397
TI  - High sensitive vectorial B-probe for low frequency plasma waves.
AB  - A miniaturized multidimensional magnetic probe is developed for application in a
      low-temperature plasma environment. A very high sensitivity for low-frequency
      magnetic field fluctuations with constant phase run, a very good signal-to-noise
      ratio combined with an efficient electrostatic pickup rejection, renders the
      probe superior compared with any commercial solution. A two-step calibration
      allows for absolute measurement of amplitude and direction of magnetic field
      fluctuations. The excellent probe performance is demonstrated by measurements of
      the parallel current pattern of coherent electrostatic drift wave modes in the
      VINETA (versatile instrument for studies on nonlinearity, electromagnetism,
      turbulence, and applications) experiment. 

PMID- 24289398
TI  - Scanning probe image wizard: a toolbox for automated scanning probe microscopy
      data analysis.
AB  - We describe SPIW (scanning probe image wizard), a new image processing toolbox
      for SPM (scanning probe microscope) images. SPIW can be used to automate many
      aspects of SPM data analysis, even for images with surface contamination and step
      edges present. Specialised routines are available for images with atomic or
      molecular resolution to improve image visualisation and generate statistical data
      on surface structure. 

PMID- 24289399
TI  - Development of an adaptable coherent x-ray diffraction microscope with the
      emphasis on imaging hydrated specimens.
AB  - This paper describes the development of a versatile coherent x-ray diffraction
      microscope capable of imaging biological specimens in solution. The microscope is
      a flexible platform accommodating various conditions, from low vacuum (10(-2) Pa)
      to helium gas filled ambient pressure. This flexibility greatly expands the
      application area, from in situ materials science to biology systems in their
      native state, by significantly relaxing restrictions to the sample environment.
      The coherent diffraction microscope has been used successfully to image a yeast
      cell immersed in buffer solution. We believe that the design of this coherent
      diffraction microscope can be directly adapted to various platforms such as table
      top soft x-ray laser, synchrotron x-ray sources, and x-ray free electron laser
      with minor relevant adjustments. 

PMID- 24289400
TI  - A high-stability scanning tunneling microscope achieved by an isolated tiny
      scanner with low voltage imaging capability.
AB  - We present a novel homebuilt scanning tunneling microscope (STM) with high
      quality atomic resolution. It is equipped with a small but powerful GeckoDrive
      piezoelectric motor which drives a miniature and detachable scanning part to
      implement coarse approach. The scanning part is a tiny piezoelectric tube scanner
      (industry type: PZT-8, whose d31 coefficient is one of the lowest) housed in a
      slightly bigger polished sapphire tube, which is riding on and spring clamped
      against the knife edges of a tungsten slot. The STM so constructed shows low back
      lashing and drifting and high repeatability and immunity to external vibrations.
      These are confirmed by its low imaging voltages, low distortions in the spiral
      scanned images, and high atomic resolution quality even when the STM is placed on
      the ground of the fifth floor without any external or internal vibration
      isolation devices. 

PMID- 24289401
TI  - Mechanical-plowing-based high-speed patterning on hard material via advanced
      control and ultrasonic probe vibration.
AB  - In this paper, we present a high-speed direct pattern fabrication on hard
      materials (e.g., a tungsten-coated quartz substrate) via mechanical plowing.
      Compared to other probe-based nanolithography techniques based on chemical-
      and/or physical-reactions (e.g., the Dip-pen technique), mechanical plowing is
      meritorious for its low cost, ease of process control, and capability of working
      with a wide variety of materials beyond conductive and/or soft materials.
      However, direct patterning on hard material faces two daunting challenges. First,
      the patterning throughput is ultimately hindered by the "writing" (plowing)
      speed, which, in turn, is limited by the adverse effects that can be
      excited/induced during high-speed, and/or large-range plowing, including the
      vibrational dynamics of the actuation system (the piezoelectric actuator, the
      cantilever, and the mechanical fixture connecting the cantilever to the
      actuator), the dynamic cross-axis coupling between different axes of motion, and
      the hysteresis and the drift effects related to the piezoelectric actuators.
      Secondly, it is very challenging to directly pattern on ultra-hard materials via
      plowing. Even with a diamond probe, the line depth of the pattern via continuous
      plowing on ultra-hard materials such as tungsten, is still rather small (<0.5
      nm), particularly when the "writing" speed becomes high. To overcome these two
      challenges, we propose to utilize a novel iterative learning control technique to
      achieve precision tracking of the desired pattern during high-speed, large-range
      plowing, and introduce ultrasonic vibration of the probe in the normal (vertical)
      direction during the plowing process to enable direct patterning on ultra hard
      materials. The proposed approach was implemented to directly fabricate patterns
      on a mask with tungsten coating and quartz substrate. The experimental results
      demonstrated that a large-size pattern of four grooves (20 MUm in length with 300
      nm spacing between lines) can be fabricated at a high speed of ~5 mm/s, with the
      line width and the line depth at ~95 nm and 2 nm, respectively. A fine pattern of
      the word "NANO" is also fabricated at the speed of ~5 mm/s.

PMID- 24289402
TI  - Actuation of atomic force microscopy microcantilevers using contact acoustic
      nonlinearities.
AB  - A new method of actuating atomic force microscopy (AFM) cantilevers is proposed
      in which a high frequency (>5 MHz) wave modulated by a lower frequency (~300 kHz)
      wave passes through a contact acoustic nonlinearity at the contact interface
      between the actuator and the cantilever chip. The nonlinearity converts the high
      frequency, modulated signal to a low frequency drive signal suitable for
      actuation of tapping-mode AFM probes. The higher harmonic content of this signal
      is filtered out mechanically by the cantilever transfer function, providing for
      clean output. A custom probe holder was designed and constructed using rapid
      prototyping technologies and off-the-shelf components and was interfaced with an
      Asylum Research MFP-3D AFM, which was then used to evaluate the performance
      characteristics with respect to standard hardware and linear actuation
      techniques. Using a carrier frequency of 14.19 MHz, it was observed that the
      cantilever output was cleaner with this actuation technique and added no
      significant noise to the system. This setup, without any optimization, was
      determined to have an actuation bandwidth on the order of 10 MHz, suitable for
      high speed imaging applications. Using this method, an image was taken that
      demonstrates the viability of the technique and is compared favorably to images
      taken with a standard AFM setup.

PMID- 24289403
TI  - Accurate spring constant calibration for very stiff atomic force microscopy
      cantilevers.
AB  - There are many atomic force microscopy (AFM) applications that rely on
      quantifying the force between the AFM cantilever tip and the sample. The AFM does
      not explicitly measure force, however, so in such cases knowledge of the
      cantilever stiffness is required. In most cases, the forces of interest are very
      small, thus compliant cantilevers are used. A number of methods have been
      developed that are well suited to measuring low stiffness values. However, in
      some cases a cantilever with much greater stiffness is required. Thus, a direct,
      traceable method for calibrating very stiff (approximately 200 N/m) cantilevers
      is presented here. The method uses an instrumented and calibrated nanoindenter to
      determine the stiffness of a reference cantilever. This reference cantilever is
      then used to measure the stiffness of a number of AFM test cantilevers. This
      method is shown to have much smaller uncertainty than previously proposed
      methods. An example application to fracture testing of nanoscale silicon beam
      specimens is included. 

PMID- 24289404
TI  - A high-speed vertical optical trap for the mechanical testing of living cells at
      piconewton forces.
AB  - Although atomic force microscopy is often the method of choice to probe the
      mechanical response of (sub)micrometer sized biomaterials, the lowest force that
      can be reliably controlled is limited to ~0.1 nN. For soft biological samples,
      like cells, such forces can already lead to a strain large enough to enter the
      non-elastic deformation regime. To be able to investigate the response of single
      cells at lower forces we developed a vertical optical trap. The force can be
      controlled down to single piconewtons and most of the advantages of atomic force
      microscopy are maintained, such as the symmetrical application of forces at a
      wide range of loading rates. Typical consequences of moving the focus in the
      vertical direction, like the interferometric effect between the bead and the
      coverslip and a shift of focus, were quantified and found to have negligible
      effects on our measurements. With a fast responding force feedback loop we can
      achieve deformation rates as high as 50 MUm/s, which allow the investigation of
      the elastic and viscous components of very soft samples. The potential of the
      vertical optical trap is demonstrated by measuring the linearity of the response
      of single cells at very low forces and a high bandwidth of deformation rates.

PMID- 24289405
TI  - Spear-anvil point-contact spectroscopy in pulsed magnetic fields.
AB  - We describe a new design and experimental technique for point-contact
      spectroscopy in non-destructive pulsed magnetic fields up to 70 T. Point-contact
      spectroscopy uses a quasi-dc four-point measurement of the current and voltage
      across a spear-anvil point-contact. The contact resistance could be adjusted over
      three orders of magnitude by a built-in fine pitch threaded screw. The first
      measurements using this set-up were performed on both single-crystalline and
      exfoliated graphite samples in a 150 ms, pulse length 70 T coil at 4.2 K and
      reproduced the well known point-contact spectrum of graphite and showed evidence
      for a developing high field excitation above 35 T, the onset field of the charge
      density wave instability in graphite.

PMID- 24289406
TI  - A compact system for generating extreme pressures and temperatures: an
      application of laser-heated diamond anvil cell to inelastic X-ray scattering.
AB  - A compact system for generating extreme pressures and temperatures was developed
      for versatile experiments based on laser-heated diamond anvil cell technique.
      This system has been used for inelastic X-ray scattering measurements for iron. 

PMID- 24289407
TI  - Compact ultrahigh vacuum sample environments for x-ray nanobeam diffraction and
      imaging.
AB  - X-ray nanobeams present the opportunity to obtain structural insight in materials
      with small volumes or nanoscale heterogeneity. The effective spatial resolution
      of the information derived from nanobeam techniques depends on the stability and
      precision with which the relative position of the x-ray optics and sample can be
      controlled. Nanobeam techniques include diffraction, imaging, and coherent
      scattering, with applications throughout materials science and condensed matter
      physics. Sample positioning is a significant mechanical challenge for x-ray
      instrumentation providing vacuum or controlled gas environments at elevated
      temperatures. Such environments often have masses that are too large for
      nanopositioners capable of the required positional accuracy of the order of a
      small fraction of the x-ray spot size. Similarly, the need to place x-ray optics
      as close as 1 cm to the sample places a constraint on the overall size of the
      sample environment. We illustrate a solution to the mechanical challenge in which
      compact ion-pumped ultrahigh vacuum chambers with masses of 1-2 kg are integrated
      with nanopositioners. The overall size of the environment is sufficiently small
      to allow their use with zone-plate focusing optics. We describe the design of
      sample environments for elevated-temperature nanobeam diffraction experiments
      demonstrate in situ diffraction, reflectivity, and scanning nanobeam imaging of
      the ripening of Au crystallites on Si substrates. 

PMID- 24289408
TI  - A multi-stage image charge detector made from printed circuit boards.
AB  - We present the first reported instance of an image-charge detector for charged
      particles in which detection elements are patterned onto printed circuit boards.
      In contrast to conventional techniques involving separately machined and
      positioned segments of metal tubing, this technique is much simpler to assemble,
      align, and connect to electrical wiring, with no loss in sensitivity. The
      performance of single-stage and 5-stage charge detectors is demonstrated using
      electrospray-charged, micrometer-size polystyrene spheres. Both velocity and
      charge of each particle are measured. Multiple detection stages--which require no
      extra effort to pattern or setup compared with a single stage--result in an
      ensemble averaging effect, improving the detection limit over what can be
      achieved with a single-stage detector. A comparison is made between the printed
      circuit board detector and a conventional tubular charge detector and found to be
      statistically equivalent. These results demonstrate and illustrate that devices
      for detection, analysis, and/or manipulation of charged particles and ions can be
      made using printed circuit boards rather than using separately fabricated metal
      electrodes.

PMID- 24289410
TI  - A portable, stable and precise laser differential refractometer.
AB  - In this work, we present a portable laser differential refractometer with real
      time detection and high precision based on the Snell's law and a 2f-2f optical
      design. The 2f-2f configuration solves a traditional position drifting problem of
      the laser beam and enhances the signal stability, where a small pinhole is
      illuminated by the laser light and imaged to the detector by lens placed in the
      middle between the detector and the pinhole. However, it also leads to a larger
      dimension of the instrument, limiting its applications and its sensitivity that
      is proportional to the optical path. Therefore, for a portable device on the
      basis of the 2f-2f design, a combination of a mirror and a lens was developed to
      minimize the optical path without affecting the 2f-2f design. Our simple and
      compact design reaches a resolution of 10(-6) refractive index units (RIU).
      Moreover, the dimension of such a modified differential refractometer is
      significantly reduced to be portable. Owing to its real-time detection speed and
      high precision, this newly developed refractometer is particularly attractive
      when it is used as an independent and ultra-sensitive detector in many research
      and industrial applications wherein there is a time-dependent concentration
      change, e.g., the concentration determination, quality control, and study of
      kinetic processes in solution, including adsorption, sedimentation, and
      dissolution, to name few but not limited. 

PMID- 24289409
TI  - An optics-based variable-temperature assay system for characterizing
      thermodynamics of biomolecular reactions on solid support.
AB  - A biological state is equilibrium of multiple concurrent biomolecular reactions.
      The relative importance of these reactions depends on physiological temperature
      typically between 10  degrees C and 50  degrees C. Experimentally the temperature
      dependence of binding reaction constants reveals thermodynamics and thus details
      of these biomolecular processes. We developed a variable-temperature opto-fluidic
      system for real-time measurement of multiple (400-10,000) biomolecular binding
      reactions on solid supports from 10  degrees C to 60  degrees C within +/-0.1 
      degrees C. We illustrate the performance of this system with investigation of
      binding reactions of plant lectins (carbohydrate-binding proteins) with 24
      synthetic glycans (i.e., carbohydrates). We found that the lectin-glycan
      reactions in general can be enthalpy-driven, entropy-driven, or both, and water
      molecules play critical roles in the thermodynamics of these reactions.

PMID- 24289411
TI  - Effusive molecular beam-sampled Knudsen flow reactor coupled to vacuum
      ultraviolet single photon ionization mass spectrometry using an external free
      radical source.
AB  - A new apparatus using vacuum ultraviolet single photon ionization mass
      spectrometry (VUV SPIMS) of an effusive molecular beam emanating from a Knudsen
      flow reactor is described. It was designed to study free radical-molecule
      kinetics over a significant temperature range (300-630 K). Its salient features
      are: (1) external free radical source, (2) counterpropagating molecular beam and
      diffuse VUV photon beam meeting in a crossed-beam ion source of a quadrupole mass
      spectrometer with perpendicular ion extraction, (3) analog detection of the
      photocurrent of the free radical molecular cation, and (4) possibility of
      detecting both free radicals and closed shell species in the same apparatus and
      under identical reaction conditions owing to the presence of photoelectrons
      generated by the photoelectric effect of the used VUV-photons. The measured
      thermal molecular beam-to-background ratio was 6.35 +/- 0.39 for Ar and 10.86 +/-
      1.59 for i-C4H10 at 300 K, a factor of 2.52 and 1.50 smaller, respectively, than
      predicted from basic gas-dynamic considerations. Operating parameters as well as
      the performance of key elements of the instrument are presented and discussed.
      Coupled to an external free radical source a steady-state specific exit flow of
      1.6 * 10(11) and 5.0 * 10(11) molecule s(-1) cm(-3) of C2H5(?) (ethyl) and t
      C4H9(?) (t-butyl) free radicals have been detected using VUV SPIMS at their
      molecular ion m/z 29 and 57, respectively, at 300 K.

PMID- 24289412
TI  - Enhanced data consistency of a portable gait measurement system.
AB  - A gait measurement system is a useful tool for rehabilitation applications. Such
      a system is used to conduct gait experiments in large workplaces such as
      laboratories where gait measurement equipment can be permanently installed.
      However, a gait measurement system should be portable if it is to be used in
      clinics or community centers for aged people. In a portable gait measurement
      system, the workspace is limited and landmarks on a subject may not be visible to
      the cameras during experiments. Thus, we propose a virtual-marker function to
      obtain positions of unseen landmarks for maintaining data consistency. This work
      develops a portable clinical gait measurement system consisting of lightweight
      motion capture devices, force plates, and a walkway assembled from plywood
      boards. We evaluated the portable clinic gait system with 11 normal subjects in
      three consecutive days in a limited experimental space. Results of gait analysis
      based on the verification of within-day and between-day coefficients of multiple
      correlations show that the proposed portable gait system is reliable. 

PMID- 24289413
TI  - High resolution autofocus for spatial temporal biomedical research.
AB  - Maintaining focus has been a critical but challenging issue in optical
      microscopy, particularly for microscopic imaging systems currently used in
      biomedical research. During live cell imaging, environmental temperature
      fluctuations and other factors contribute to the unavoidable focus drift. For
      single molecular imaging and super resolution, focus drift can be significant
      even over short durations. The current commercial and experimental solutions are
      either optically complicated, expensive, or with limited axial resolution. Here,
      we present a simple autofocus solution based on low cost solid state laser and
      imaging sensor. By improving the optical train design and using real-time data
      analysis, improvement in axial resolution by approximately two orders of
      magnitudes over the focal depth of microscope objectives can be achieved. This
      solution has been tested for prolonged live cell imaging for fast ramping up in
      environmental chamber temperature and large daily swing in room temperature. In
      addition, this system can be used to spatial-temporally measure the surface for
      three-dimensional cell culture and tissue engineering, with flexibility that
      exceeds commercially available systems. 

PMID- 24289414
TI  - Apparatus for simulating dynamic interactions between the spinal cord and soft
      coupled intradural implants.
AB  - We have designed, built, and tested an apparatus used for investigating the
      biomechanical response of a novel intradural spinal cord stimulator to the
      simulated physiological movement of the spinal cord within the thecal sac. In
      this apparatus, the rostral-caudal displacements of an anthropomorphic spinal
      cord surrogate can be controlled with a resolution of approximately 0.1% of a
      target value for up to 10(7) lateral movement cycles occurring at a repetition
      rate of 2 Hz. Using this system, we have been able to determine that the
      restoring force of the stimulator's suspension system works in concert with the
      frictional coupling between the electrode array and the surrogate to overcome the
      0.42 MUN inertial force associated with the lateral motion of the array. The
      result is a positional stability of the array on the surrogate (in air) of better
      than 0.2 mm over ~500,000 movement cycles. Design modifications that might lead
      to improved physiological performance are discussed.

PMID- 24289417
TI  - Radio-transparent multi-layer insulation for radiowave receivers.
AB  - In the field of radiowave detection, enlarging the receiver aperture to enhance
      the amount of light detected is essential for greater scientific achievements.
      One challenge in using radio transmittable apertures is keeping the detectors
      cool. This is because transparency to thermal radiation above the radio frequency
      range increases the thermal load. In shielding from thermal radiation, a general
      strategy is to install thermal filters in the light path between aperture and
      detectors. However, there is difficulty in fabricating metal mesh filters of
      large diameters. It is also difficult to maintain large diameter absorptive-type
      filters in cold because of their limited thermal conductance. A technology that
      maintains cold conditions while allowing larger apertures has been long-awaited.
      We propose radio-transparent multi-layer insulation (RT-MLI) composed from a set
      of stacked insulating layers. The insulator is transparent to radio frequencies,
      but not transparent to infrared radiation. The basic idea for cooling is similar
      to conventional multi-layer insulation. It leads to a reduction in thermal
      radiation while maintaining a uniform surface temperature. The advantage of this
      technique over other filter types is that no thermal links are required. As
      insulator material, we used foamed polystyrene; its low index of refraction makes
      an anti-reflection coating unnecessary. We measured the basic performance of RT
      MLI to confirm that thermal loads are lowered with more layers. We also confirmed
      that our RT-MLI has high transmittance to radiowaves, but blocks infrared
      radiation. For example, RT-MLI with 12 layers has a transmittance greater than
      95% (lower than 1%) below 200 GHz (above 4 THz). We demonstrated its effects in a
      system with absorptive-type filters, where aperture diameters were 200 mm. Low
      temperatures were successfully maintained for the filters. We conclude that this
      technology significantly enhances the cooling of radiowave receivers, and is
      particularly suitable for large-aperture systems. This technology is expected to
      be applicable to various fields, including radio astronomy, geo-environmental
      assessment, and radar systems. 

PMID- 24289416
TI  - Compact low resolution spectrograph, an imaging and long slit spectrograph for
      robotic telescopes.
AB  - The COmpact LOw REsolution Spectrograph (COLORES) is a compact and lightweight
      (13 kg) f/8 imaging spectrograph designed for robotic telescopes, now installed
      and operating on the TELMA, a rapid-slewing 60 cm telescope of the BOOTES-2
      observatory in Malaga (Spain). COLORES is a multi-mode instrument that enables
      the observer to seamlessly switch between low-dispersion spectroscopy and direct
      imaging modes during an observation. In this paper, we describe the instrument
      and its development, from the initial scientific requirements through the optical
      design process to final configuration with theoretical performance calculations.
      The mechanical and electronic design is described, methods of calibration are
      discussed and early laboratory and scientific results are shown.

PMID- 24289415
TI  - Uniaxial cell stretching device for live-cell imaging of mechanosensitive
      cellular functions.
AB  - External mechanical stretch plays an important role in regulating cellular
      behaviors through intracellular mechanosensitive and mechanotransductive
      machineries such as the F-actin cytoskeleton (CSK) structures and focal adhesions
      (FAs) anchoring the F-actin CSK to the extracellular environment. Studying the
      mechanoresponsive behaviors of the F-actin CSK and FAs in response to cell
      stretch has great importance for further understanding mechanotransduction and
      mechanobiology. In this work, we developed a novel cell stretching device
      combining dynamic directional cell stretch with in situ subcellular live-cell
      imaging. Using a cam and follower mechanism and applying a standard mathematical
      model for cam design, we generated different dynamic stretch outputs. By
      examining stretch-mediated FA dynamics under step-function static stretch and the
      realignment of cell morphology and the F-actin CSK under cyclic stretch, we
      demonstrated successful applications of our cell stretching device for
      mechanobiology studies where external stretch plays an important role in
      regulating subcellular molecular dynamics and cellular phenotypes. 

PMID- 24289418
TI  - Triaxial testing system for pressure core analysis using image processing
      technique.
AB  - In this study, a newly developed innovative triaxial testing system to
      investigate strength, deformation behavior, and/or permeability of gas hydrate
      bearing-sediments in deep sea is described. Transport of the pressure core from
      the storage chamber to the interior of the sealing sleeve of a triaxial cell
      without depressurization was achieved. An image processing technique was used to
      capture the motion and local deformation of a specimen in a transparent acrylic
      triaxial pressure cell and digital photographs were obtained at each strain level
      during the compression test. The material strength was successfully measured and
      the failure mode was evaluated under high confining and pore water pressures.

PMID- 24289419
TI  - Theoretical and experimental analysis of a linear accelerator endowed with single
      feed coupler with movable short-circuit.
AB  - The front-end injection systems of the FERMI@Elettra linac produce high
      brightness electron beams that define the performance of the Free Electron Laser.
      The photoinjector mainly consists of the radiofrequency (rf) gun and of two S
      band rf structures which accelerate the beam. Accelerating structures endowed
      with a single feed coupler cause deflection and degradation of the electron beam
      properties, due to the asymmetry of the electromagnetic field. In this paper, a
      new type of single feed structure with movable short-circuit is proposed. It has
      the advantage of having only one waveguide input, but we propose a novel design
      where the dipolar component is reduced. Moreover, the racetrack geometry allows
      to reduce the quadrupolar component. This paper presents the microwave design and
      the analysis of the particle motion inside the linac. A prototype has been
      machined at the Elettra facility to verify the new coupler design and the rf
      field has been measured by adopting the bead-pull method. The results are here
      presented, showing good agreement with the expectations.

PMID- 24289420
TI  - A TE01 mode generator for testing high power transmission devices.
AB  - To verify the performance of high power waveguide transmission devices such as
      the miter bend, the waveguide taper, and the quasi-optical mode converter by the
      low power measurement, a TE01 mode generator, converts the rectangular waveguide
      TE10 mode into the cylindrical waveguide TE01 mode, for Ka-band is designed,
      fabricated, and measured. The proposed generator consists of a TE10 to TE20
      rectangular waveguide mode converter and a rectangular TE20 to circular TE01 mode
      converter. The converting process in each section is analyzed and the working
      principles are discussed. Two prototypes are built and tested. The back-to-back
      transmission measured results agree well with the numerical calculations. The
      measured optimum transmissions are 97% with a 1-dB bandwidth from 29.2 GHz to
      31.6 GHz. The angle-independent transmissions demonstrate high mode purity and
      the presence of TE01 mode confirmed by the far-field measurement. The proposed
      mode generator features high conversion efficiency, high mode purity, and
      moderate broad bandwidth. 

PMID- 24289421
TI  - Microwave resonances in dielectric samples probed in Corbino geometry: simulation
      and experiment.
AB  - The Corbino approach, where the sample of interest terminates a coaxial cable, is
      a well-established method for microwave spectroscopy. If the sample is dielectric
      and if the probe geometry basically forms a conductive cavity, this combination
      can sustain well-defined microwave resonances that are detrimental for broadband
      measurements. Here, we present detailed simulations and measurements to
      investigate the resonance frequencies as a function of sample and probe size and
      of sample permittivity. This allows a quantitative optimization to increase the
      frequency of the lowest-lying resonance. 

PMID- 24289422
TI  - Improvement of vibration energy harvesters through a two-stage design: power
      production at single frequency excitation.
AB  - A vibration harvester is usually designed to work in resonance responding to
      source vibration. Many existing types of harvesters use a single mechanical
      resonator to amplify the excitation vibrations. However, these harvesters are
      inherently limited in the amount of power that they can produce, due to their
      design, particularly in the limited number of design parameters. In our study, we
      propose a two-stage design to improve a harvester's performance both in power
      production and in bandwidth widening. In this paper, we demonstrate that a two
      stage design can increase the power production when the device is intended to
      operate under a single frequency excitation. Harvester parameters are optimized
      to provide maximum power production. Power production comparisons between single
      stage and two-stage harvesters are made through numerical simulation and
      experiments. 

PMID- 24289423
TI  - A compact bipolar pulse-forming network-Marx generator based on pulse
      transformers.
AB  - A compact bipolar pulse-forming network (PFN)-Marx generator based on pulse
      transformers is presented in this paper. The high-voltage generator consisted of
      two sets of pulse transformers, 6 stages of PFNs with ceramic capacitors, a
      switch unit, and a matched load. The design is characterized by the bipolar pulse
      charging scheme and the compact structure of the PFN-Marx. The scheme of bipolar
      charging by pulse transformers increased the withstand voltage of the ceramic
      capacitors in the PFNs and decreased the number of the gas gap switches. The
      compact structure of the PFN-Marx was aimed at reducing the parasitic inductance
      in the generator. When the charging voltage on the PFNs was 35 kV, the matched
      resistive load of 48 Omega could deliver a high-voltage pulse with an amplitude
      of 100 kV. The full width at half maximum of the load pulse was 173 ns, and its
      rise time was less than 15 ns. 

PMID- 24289424
TI  - Research of an electromagnetically actuated spark gap switch.
AB  - As an important part of pulsed power systems, high-voltage and high-current
      triggered spark gap switch and its trigger system are expected to achieve a
      compact structure. In this paper, a high-voltage, high-current, and compact
      electromagnetically actuated spark gap switch is put forward, and it can be
      applied as a part of an intense electron-beam accelerator (IEBA). A 24 V DC power
      supply is used to trigger the switch. The characteristics of the switch were
      measured for N2 when the gas pressure is 0.10-0.30 MPa. The experimental results
      showed that the voltage/pressure (V/p) curve of the switch was linear
      relationship. The operating ranges of the switch were 21%-96%, 21%-95%, 21%-95%,
      19%-95%, 17%-95%, and 16%-96% of the switch's self-breakdown voltage when the gas
      pressures were 0.10, 0.14, 0.18, 0.22, 0.26, and 0.30 MPa, respectively. The
      switch and its trigger system worked steadily and reliably with a peak voltage of
      30 kV, a peak current of 60 kA in the IEBA when the pressure of N2 in the switch
      was 0.30 MPa.

PMID- 24289425
TI  - Sub-picowatt/kelvin resistive thermometry for probing nanoscale thermal
      transport.
AB  - Advanced instrumentation in thermometry holds the key for experimentally probing
      fundamental heat transfer physics. However, instrumentation with simultaneously
      high thermometry resolution and low parasitic heat conduction is still not
      available today. Here we report a resistive thermometry scheme with ~50 MUK
      temperature resolution and ~0.25 pW/K thermal conductance resolution, which is
      achieved through schemes using both modulated heating and common mode noise
      rejection. The suspended devices used herein have been specifically designed to
      possess short thermal time constants and minimal attenuation effects associated
      with the modulated heating current. Furthermore, we have systematically
      characterized the parasitic background heat conductance, which is shown to be
      significantly reduced using the new device design and can be effectively
      eliminated using a "canceling" scheme. Our results pave the way for probing
      fundamental nanoscale thermal transport processes using a general scheme based on
      resistive thermometry.

PMID- 24289426
TI  - Spectral decomposition of phosphorescence decays.
AB  - In phosphor thermometry, the fitting of decay curves is a key task in the robust
      and precise determination of temperatures. These decays are generally assumed to
      be mono-exponential in certain temporal boundaries, where fitting is performed.
      The present study suggests a multi-exponential method to determine the spectral
      distribution in terms of decay times in order to analyze phosphorescence decays
      and thereby complement the mono-exponential analysis. Therefore, two methods of
      choice are compared and verified using simulated data in the presence of noise.
      Addtionally, this spectral decomposition is applied to the thermographic phosphor
      Mg4FGeO6 : Mn and reveals changes in the exponential distributions of decay times
      upon a change of the excitation laser energy. 

PMID- 24289427
TI  - A method for testing the integrated thermal resistance of thermoelectric modules.
AB  - The integrated thermal resistance (ITR) of thermoelectric modules (TEMs) is an
      important parameter that represents the thermal-conduction of ceramic substrates,
      copper conducting strips, and welding material used in the TEM as well as the
      thermal contact resistances between different materials. In this study, an
      accurate and practical test method is proposed for the ITR of TEMs according to
      thermoelectric heat transfer theory and the equivalent characteristics of heat
      flux through the cold and hot sides of TEMs in an open-circuit situation. By
      using such measurements and comparisons, it is verified that the measured ITR
      value in our mode is accurate and reliable. In particular this method accurately
      predicts the actual operating conditions of TEMs, in which TEMs are under certain
      mechanical pressure. It effectively solves the problem of thermal resistance
      extraction from operating TEMs and is of great significance in their analysis and
      optimization. 

PMID- 24289428
TI  - Study of cross-shaped ultrasonic array sensor applied to partial discharge
      location in transformer oil.
AB  - A conformal combined sensor is designed and it is used in Partial Discharge (PD)
      location experiments in transformer oil. The sensor includes a cross-shaped
      ultrasonic phased array of 13 elements and an ultra-high-frequency (UHF)
      electromagnetic rectangle array of 2 * 2 elements. Virtual expansion with high
      order cumulants, the ultrasonic array can achieve the effect of array with 61
      elements. This greatly improves the aperture and direction sharpness of original
      array and reduces the cost of follow-up hardware. With the cross-shaped
      ultrasonic array, the results of PD location experiments are precise and the
      maximum error of the direction of arrival (DOA) is less than 5 degrees . 

PMID- 24289429
TI  - Absolute distance sensing by two laser optical interferometry.
AB  - We have developed a method for absolute distance sensing by two laser optical
      interferometry. A particularity of this technique is that a target distance is
      determined in absolute and is no longer limited to within an ambiguity range
      affecting usually multiple wavelength interferometers. We implemented the
      technique in a low-finesse Fabry-Perot miniature fiber based interferometer. We
      used two diode lasers, both operating in the 1550 nm wavelength range. The
      wavelength difference is chosen to create a 25 MUm long periodic beating
      interferometric pattern allowing a nanometer precise position measurement but
      limited to within an ambiguity range of 25 MUm. The ambiguity is then eliminated
      by scanning one of the wavelengths over a small range (3.4 nm). We measured
      absolute distances in the sub-meter range and this with just few nanometer
      repeatability.

PMID- 24289430
TI  - Inverse compensation for hysteresis in piezoelectric actuator using an asymmetric
      rate-dependent model.
AB  - This paper presents a modified Bouc-Wen model for asymmetric rate-dependent
      hysteresis in piezoelectric actuator. On this basis, we develop a new digital
      inverse controller with a simple structure cascaded in the feedforward path for
      piezoelectric actuator. In order to eliminate modeling errors and parameter
      uncertainties, the developed inverse controller is combined with a feedback loop
      to establish a hybrid control scheme. In our experiments, the proposed model
      together with the developed hybrid control scheme has shown significantly reduced
      tracking errors caused by asymmetric rate-dependent hysteresis in piezoelectric
      actuator. 

PMID- 24289431
TI  - Generalized lock-in amplifier for precision measurement of high frequency
      signals.
AB  - We herein formulate the concept of a generalized lock-in amplifier for the
      precision measurement of high frequency signals based on digital cavities.
      Accurate measurement of signals higher than 200 MHz using the generalized lock-in
      is demonstrated. The technique is compared with a traditional lock-in and its
      advantages and limitations are discussed. We also briefly point out how the
      generalized lock-in can be used for precision measurement of giga-hertz signals
      by using parallel processing of the digitized signals. 

PMID- 24289432
TI  - Methods for quantifying the influences of pressure and temperature variation on
      metal hydride reaction rates measured under isochoric conditions.
AB  - Analysis techniques for determining gas-solid reaction rates from gas sorption
      measurements obtained under non-constant pressure and temperature conditions
      often neglect temporal variations in these quantities. Depending on the materials
      in question, this can lead to significant variations in the measured reaction
      rates. In this work, we present two new analysis techniques for comparison
      between various kinetic models and isochoric gas measurement data obtained under
      varying temperature and pressure conditions in a high pressure Sievert system. We
      introduce the integral pressure dependence method and the temperature dependence
      factor as means of correcting for experimental variations, improving model
      measurement fidelity, and quantifying the effect that such variations can have on
      measured reaction rates. We use measurements of hydrogen absorption in LaNi5 and
      TiCrMn to demonstrate the effect of each of these methods and show that their use
      can provide quantitative improvements in interpretation of kinetics measurements.

PMID- 24289433
TI  - Optimal design and experiment of a three-axis out-of-plane nano positioning stage
      using a new compact bridge-type displacement amplifier.
AB  - This paper presents the development of a new compact three-axis compliant stage
      employing piezoelectric actuators and a new flexure structure. A proposed stage
      works out-of-plane (Z, thetax, thetay) direction. The stage consists of 4
      amplification flexures mounted piezoelectric actuators. New structure of flexure
      reduces height and enhances dynamic performance of stage. To certify excellent
      performance of the stage, comparison accomplished between conventional
      amplification flexure and new compact bridge type flexure. Modeling and optimal
      design of new type nano positioning stage performed. The optimal design is
      executed on the geometric parameters of the proposed flexure structure using
      Sequential Quadratic Programming. Experiments are carried out to verify the
      static and dynamic performance of the stage. The proposed out-of-plane nano
      positioning stage has a Z-directional motion range 190 MUm and a thetax, thetay
      directional motion range +/-2 mrad. The resolution of the stage is 4 nm, 40 nrad,
      and 40 nrad in the Z-, thetax-, and thetay-directional motions, respectively. The
      size of stage is 150 * 150 * 30 mm(3). 

PMID- 24289434
TI  - A simple constrained uniaxial tensile apparatus for in situ investigation of film
      stretching processing.
AB  - A simple constrained uniaxial tensile apparatus was designed and constructed to
      obtain stress-strain curve during stretching and subsequent structural evolution
      of polymeric films. Stretch is carried out through two motor driven clamps in the
      machine direction and scissor-like clamps in the transverse direction keeping the
      sample width constant. The force information during film stretching process is
      recorded by a tension sensor and structural evolution can be obtained by in situ
      X-ray scattering technique. All parameters related to film stretching
      manufacturing, such as temperature, draw ratio, and stretching speed can be set
      independently, making the apparatus an effective method to explore the
      relationship between processing parameters and structure. 

PMID- 24289435
TI  - Robofurnace: a semi-automated laboratory chemical vapor deposition system for
      high-throughput nanomaterial synthesis and process discovery.
AB  - Laboratory research and development on new materials, such as nanostructured thin
      films, often utilizes manual equipment such as tube furnaces due to its
      relatively low cost and ease of setup. However, these systems can be prone to
      inconsistent outcomes due to variations in standard operating procedures and
      limitations in performance such as heating and cooling rates restrict the
      parameter space that can be explored. Perhaps more importantly, maximization of
      research throughput and the successful and efficient translation of materials
      processing knowledge to production-scale systems, relies on the attainment of
      consistent outcomes. In response to this need, we present a semi-automated lab
      scale chemical vapor deposition (CVD) furnace system, called "Robofurnace."
      Robofurnace is an automated CVD system built around a standard tube furnace,
      which automates sample insertion and removal and uses motion of the furnace to
      achieve rapid heating and cooling. The system has a 10-sample magazine and
      motorized transfer arm, which isolates the samples from the lab atmosphere and
      enables highly repeatable placement of the sample within the tube. The system is
      designed to enable continuous operation of the CVD reactor, with asynchronous
      loading/unloading of samples. To demonstrate its performance, Robofurnace is used
      to develop a rapid CVD recipe for carbon nanotube (CNT) forest growth, achieving
      a 10-fold improvement in CNT forest mass density compared to a benchmark recipe
      using a manual tube furnace. In the long run, multiple systems like Robofurnace
      may be linked to share data among laboratories by methods such as Twitter. Our
      hope is Robofurnace and like automation will enable machine learning to optimize
      and discover relationships in complex material synthesis processes. 

PMID- 24289436
TI  - Measuring non-condensable gases in steam.
AB  - In surgery, medical devices that are used should be sterilized. To obtain surface
      steam sterilization conditions, not only in the sterilizer chamber itself but
      also in the loads to be sterilized, the amount of non-condensable gases (NCGs),
      for instance air, should be very low. Even rather small fractions of NCGs (below
      1%) seriously hamper steam penetration in porous materials or devices with hollow
      channels (e.g., endoscopes). A recently developed instrument which might detect
      the presence of residual NCGs in a reliable and reproducible way is the 3M(TM)
      Electronic Test System (ETS). In this paper, a physical model is presented that
      describes the behavior of this instrument. This model has been validated by
      experiments in which known fractions of NCGs were introduced in a sterilizer
      chamber in which an ETS was placed. Despite several approximations made in the
      model, a good agreement is found between the model predictions and the
      experimental results. The basic principle of the ETS, measuring the heat transfer
      by condensation on a cooled surface, permits a very sensitive detection of NCGs
      in harsh environments like water vapor at high temperatures and pressures. Our
      model may serve to develop adapted and optimized versions of this instrument for
      use outside the field of sterilization, e.g., in heat exchangers based on steam
      condensation.

PMID- 24289437
TI  - Characterization of multi-dye pressure-sensitive microbeads.
AB  - The response times of pressure-sensitive particles to passing shockwaves were
      measured to investigate their ability to accurately determine pressure changes in
      unsteady flows. The particles tested were loaded with novel pressure-sensitive
      dyes such as Pt (II) meso-tetra(pentafluorophenyl)porphine, Pt(II)
      octaethylporphine, bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2
      carboxypyridyl))iridium III, and iridium(III) bis(4-phenylthieno[3,2-c]
      pyridinato-N,C2')acetylacetonate. For this work, porous silicon dioxide pressure
      sensitive beads (PSBeads) were used. Two synthetic procedures were used to
      fabricate the particles. In the first, a one-step method loaded dyes during the
      synthesis of microbeads, in the second a two-step method synthesized the
      microbeads first, then loaded the dyes. The shock tube facility was used to
      measure the response times of microbeads to fast pressure jumps. The study
      involved testing multiple luminophors loaded in microbeads with various size
      distributions. Response times for the silica-based microbeads ranged between 26
      MUs and 462 MUs (at 90% of the amplitude response), which are much faster than
      previously reported polystyrene-based microbead response times, which range from
      507 MUs to 1582 MUs (at 90% of the amplitude response) [F. Kimura, M. Rodriguez,
      J. McCann, B. Carlson, D. Dabiri, G. Khalil, J. B. Callis, Y. Xia, and M.
      Gouterman, "Development and characterization of fast responding pressure
      sensitive microspheres," Rev. Sci. Instrum. 79, 074102 (2008)]. 

PMID- 24289438
TI  - Simulation-guided optimization of small-angle analyzer geometry in the neutron
      backscattering spectrometer SPHERES.
AB  - The resolution of neutron backscattering spectrometers deteriorates at small
      scattering angles where analyzers deviate from exact backscattering. By reducing
      the azimuth angle range of the analyzers, the resolution can be improved with
      little loss of peak intensity. Measurements at the spectrometer SPHERES are in
      excellent agreement with simulations, which proves the dominance of geometric
      effects. 

PMID- 24289439
TI  - Reconfigurable acquisition system with integrated optics for a portable flow
      cytometer.
AB  - Portable and inexpensive scientific instruments that are capable of performing
      point of care diagnostics are needed for applications such as disease detection
      and diagnosis in resource-poor settings, for water quality and food supply
      monitoring, and for biosurveillance activities in autonomous vehicles. In this
      paper, we describe the development of a compact flow cytometer built from three
      separate, customizable, and interchangeable modules. The instrument as configured
      in this work is being developed specifically for the detection of selected
      Centers for Disease Control (CDC) category B biothreat agents through a bead
      based assay: E. coli O157:H7, Salmonella, Listeria, and Shigella. It has two
      color excitation, three-color fluorescence and light scattering detection,
      embedded electronics, and capillary based flow. However, these attributes can be
      easily modified for other applications such as cluster of differentiation 4 (CD4)
      counting. Proof of concept is demonstrated through a 6-plex bead assay with the
      results compared to a commercially available benchtop-sized instrument. 

PMID- 24289440
TI  - A temperature dependent screening tool for high throughput thermoelectric
      characterization of combinatorial films.
AB  - Combinatorial metrology has evolved as a useful approach to rapidly determine the
      composition-structure-property relationships for solid solution systems in a far
      more efficient way than the traditional one composition at a time approach. The
      success of this method applied in thermoelectric (TE) research relies on
      screening tools to evaluate the TE properties for a combinatorial library. We
      report here on a thermoelectric screening tool capable of performing temperature
      dependent measurement of the Seebeck coefficient and electrical resistivity from
      300 K to 800 K. The validity of the apparatus is demonstrated by screening the
      power factor of a filled skutterudite combinatorial film at room temperature and
      at elevated temperatures as well. The accuracy of the measurement is verified
      using the low temperature Seebeck coefficient Standard Reference Material (NIST
      SRM 3451) and a heavily doped SiGe specimen for high temperature comparison.
      Several important parameters, such as measurement atmosphere, film substrate, and
      probe configuration, are identified that directly affect the Seebeck coefficient
      measurement in this and other similar apparatus. 

PMID- 24289441
TI  - A two degree of freedom micro-gripper with grasping and rotating functions for
      optical fibers assembling.
AB  - In this paper, a two degree of freedom flexure-based micro-gripper is proposed
      and applied in the complicated assembling process of optical fibers. The design
      concept is modeled on the manipulation of human fingers. Therefore, the two tips
      of micro-gripper, just like human fingers, can easily grasp the optical fiber
      with a controllable force and precisely rotate it by the rubbing operation. In
      addition, some sensors installed on the micro-gripper can enhance the operating
      accuracy. In the developing process, pseudo-rigid-body model method and virtual
      work principle are employed to conduct theoretical design. Then the obtained
      theoretical model is validated and optimized by the finite element analysis.
      Fabrication of the micro-gripper adopts wire electro discharge machining
      technology and material of aluminum alloy (AL-7075). Experimental studies are
      carried out on the prototype to further validate the performance of micro
      gripper. Experimental results indicate that the developed micro-gripper can well
      satisfy the requirements of our mission, which also means that it can be widely
      used in micro-manipulation field. 

PMID- 24289442
TI  - Note: Production of a mercury beam with an electron cyclotron resonance ion
      source.
AB  - An electron cyclotron resonance ion source has been utilized to produce mercury
      beams with intensities of 4.5 eMUA of (202)Hg(29+) and 3.0 eMUA of (202)Hg(31+)
      from natural abundance mercury metal. The production technique relies on the
      evaporation of liquid mercury into the source plasma vacuum region and utilizes
      elemental mercury instead of a volatile organic compound as the neutral feed
      material. 

PMID- 24289443
TI  - Note: Design and development of an integrated three-dimensional scanner for
      atomic force microscopy.
AB  - A compact scanning head for the Atomic Force Microscope (AFM) greatly enhances
      the portability of AFM and facilitates easy integration with other tools. This
      paper reports the design and development of a three-dimensional (3D) scanner
      integrated into an AFM micro-probe. The scanner is realized by means of a novel
      design for the AFM probe along with a magnetic actuation system. The integrated
      scanner, the actuation system, and their associated mechanical mounts are
      fabricated and evaluated. The experimentally calibrated actuation ranges are
      shown to be over 1 MUm along all the three axes. 

PMID- 24289444
TI  - Note: Compact, two-dimension translatable slit aperture.
AB  - A compact, light-weight, two-dimension translatable slit aperture is described.
      The slit dimensions are scalable, allowing for wide application. With all metal
      construction, the device would be suitable for high temperature degassing and
      vacuum compatible. Alternatively, the main structure may be printed using a 3D
      printer for rapid prototyping and/or lighter weight. The precision of the slit
      movement is 0.014 mm.

PMID- 24289445
TI  - Note: Near infrared spectral and transient measurements of PbS quantum dots
      luminescence.
AB  - We describe an experimental setup for the characterization of luminescence from
      nanostructures. The setup is intended for steady-state and time-resolved
      luminescence measurements in the near-infrared region. The setup allows us to
      study spectral luminescence properties in the spectral range of 0.8-2.0 MUm with
      high spectral resolution and kinetic luminescence properties between 0.8 and 1.7
      MUm with a time resolution of 3 ns. The capabilities of the system are
      illustrated by taking luminescence measurements from PbS quantum dots. We
      established the size dependencies of the optical properties of the PbS quantum
      dots over a wide spectral range. Finally, the energy transfer process was studied
      with a high temporal and spectral resolution. 

PMID- 24289446
TI  - Note: Electrical modeling and characterization of voltage gradient in liquid
      crystal microlenses.
AB  - In this work, a novel equivalent electric circuit for modeling liquid crystal
      microlenses is proposed. This model is focused on explaining a lens behavior at
      the micrometric scale, using its manufacturing parameters. It suggests an
      approach to predict the solution of the voltage gradient distribution across a
      microlens. An interesting feature of the model is that it provides an analytical
      solution for microlenses with modal and hole-patterned electrode schemes, by a
      simple software tool. The model flexibility allows lens designers to apply
      complex waveform signals with different harmonics. The voltage distribution has
      been tested. The simulated and measured voltage profiles are fairly in agreement.

PMID- 24289447
TI  - Note: A simple model for thermal management in solenoids.
AB  - We describe a model of the dynamical temperature evolution in a solenoid winding.
      A simple finite element analysis is calibrated by accurately measuring the
      thermally induced resistance change of the solenoid, thus obviating the need for
      accurate knowledge of the mean thermal conductivity of the windings. The model
      predicts quasi thermal runaway for relatively modest current increases from the
      normal operating conditions. We demonstrate the application of this model to
      determine the maximum current that can be safely applied to solenoids used for
      helium spin-echo measurements. 

PMID- 24289448
TI  - Note: Characteristic beam parameter for the line electron gun.
AB  - We have optimized the beam parameters of line source electron gun using Stanford
      Linear Accelerator Centre electron beam trajectory program (EGUN), utilizing
      electrostatic focusing only. We measured minimum beam diameter as 0.5 mm that
      corresponds to power density of 68.9 kW/cm(2) at 13.5 mm in the post-anode region
      which is more than two-fold (33 kW/cm(2)), of the previously reported results.
      The gun was operated for the validation of the theoretical results and found in
      good agreement. The gun is now without any magnetic and electrostatic focusing
      thus much simpler and more powerful.

PMID- 24289452
TI  - Cattle movements and trypanosomes: restocking efforts and the spread of
      Trypanosoma brucei rhodesiense sleeping sickness in post-conflict Uganda.
AB  - BACKGROUND: The northwards spread of acute T. b. rhodesiense sleeping sickness in
      Uganda has been linked to cattle movements associated with restocking following
      the end to military conflict in 2006. This study examined the number of cattle
      traded from T. b. rhodesiense endemic districts, the prevalence of the parasite
      in cattle being traded and the level of trypanocidal treatment at livestock
      markets. METHODS: Between 2008 and 2009 interviews were carried out with
      government veterinarians from 20 districts in Uganda, 18 restocking organisations
      and numerous livestock traders and veterinarians. Direct observations, a review
      of movement permit records (2006 to 2008) and blood sampling of cattle (n = 1758)
      for detection of parasites were also conducted at 10 livestock markets in T. b.
      rhodesiense endemic districts. RESULTS: Records available from 8 out of 47
      identified markets showed that 39.5% (5,238/13,267) of the inter-district cattle
      trade between mid-2006 and mid-2008 involved movement from endemic areas to
      pathogen-free districts. PCR analysis showed a prevalence of 17.5% T. brucei s.l.
      (n = 307/1758 [95% CI: 15.7-19.2]) and 1.5% T. b. rhodesiense (n = 26/1758 [95%
      CI: 0.9-2.0]) from these same markets. In a two-year period, between late-2006 to
      late-2008, an estimated 72,321 to 86,785 cattle (57, 857 by 18 restocking
      organisations and 10,214 to 24,679 by private traders) were imported into seven
      pathogen-free northern districts, including districts that were endemic for T. b.
      gambiense. Between 281 and 1,302 of these cattle were likely to have carried T.
      b. rhodesiense. While governmental organisations predominantly adhered to
      trypanocidal treatment, most Non-Governmental Organisations (NGOs) and private
      traders did not. Inadequate market infrastructure, poor awareness, the need for
      payment for drug treatments, and the difficulty in enforcing a policy of
      treatment at point of sale contributed to non-compliance. CONCLUSION: With
      increasing private trade, preventing the spread of Rhodesian sleeping sickness in
      Uganda requires government support to ensure mandatory trypanocidal treatment at
      livestock markets, investment in market infrastructure and possible drug subsidy.
      Mapping the northern reaches of T. b. rhodesiense in livestock and preparation of
      risk assessments for cattle trading could mitigate future outbreaks.

PMID- 24289454
TI  - Occurrence of NDL-PCBs, DL-PCBs, PCDD/Fs, lead and cadmium in feed and in rainbow
      trout (Oncorhynchus mykiss) farmed in Italy.
AB  - The safety of farmed rainbow trout (Oncorhynchus mykiss) is correlated with the
      quality of the production process. Polychlorinated biphenyls (PCBs), dioxins
      (polychlorinated dibenzodioxins and furans - PCDD/Fs), and heavy metals such as
      lead and cadmium were investigated because they can represent a risk for the
      consumer. The levels of these compounds in water, feed and specimens of trout
      farmed with two different feeds (A and B) were assessed. Their accumulation in
      muscle of A and B trout was evaluated and their dependence on the levels of feed
      contamination was considered. The results showed a widespread contamination in
      feed and in the examined trout, although lower than the European Union limits.
      For all compounds, concentrations in the farming waters were always < LOQs. Mean
      concentrations of NDL-PCBs in the A feed were significantly higher than in the B
      feed, except for PCBs 52 and 28. DL-PCB and PCDD/F concentrations were
      significantly higher in A feed. Lead and cadmium mean concentrations in A feed
      were 0.26 +/- 0.01 and 0.1013 +/- 0.0009 ug g(-1), respectively; and in B feed
      were 0.10 +/- 0.01 and 0.0855 +/- 0.0078 ug g(-1), respectively. The results
      showed that intakes for ?DL-PCB + ?PCDD/F ranged from 4.4% to 12% of the TDI, and
      for Pb and Cd from 1.9% to 2.7% and from 0.3% to 0.4% of the TDI, respectively.

PMID- 24289455
TI  - Association of angiotensin converting enzyme gene insertion/deletion polymorphism
      and familial hypercholesterolemia in the Saudi population.
AB  - BACKGROUND: The study of the association between genotype and phenotype is of
      great importance for the prediction of multiple diseases and pathophysiological
      conditions. The relationship between angiotensin converting enzyme (ACE)
      Insertion/Deletion (I/D) polymorphism and Familial Hypercholesterolemia (FH) has
      been not fully investigated in all the ethnicities. In this study we sought to
      determine the frequency of I/D polymorphism genotypes of ACE gene in Saudi
      patients with FH. RESULTS: This is a case-control study carried out purely in
      Saudi population. Genomic DNA was isolated from 128 subjects who have
      participated in this study. ACE gene I/D polymorphism was analyzed by polymerase
      chain reaction in 64 FH cases and 64 healthy controls. There was no statistically
      significant difference between the groups with respect to genotype distribution.
      Furthermore, we did not find any significant difference in the frequency of ACE
      I/D polymorphism in FH subjects when stratified by gender (p = 0.43). CONCLUSION:
      Our data suggest that ACE gene I/D polymorphism examined in this study has no
      role in predicting the occurrence and diagnosis of FH.

PMID- 24289453
TI  - WSES guidelines for emergency repair of complicated abdominal wall hernias.
AB  - Emergency repair of complicated abdominal hernias is associated with poor
      prognosis and a high rate of post-operative complications.A World Society of
      Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013,
      during the 2nd Congress of the World Society of Emergency Surgery with the goal
      of defining recommendations for emergency repair of abdominal wall hernias in
      adults. This document represents the executive summary of the consensus
      conference approved by a WSES expert panel. 

PMID- 24289456
TI  - Quality in Acute Stroke Care (QASC): process evaluation of an intervention to
      improve the management of fever, hyperglycemia, and swallowing dysfunction
      following acute stroke.
AB  - BACKGROUND: Our randomized controlled trial of a multifaceted evidence-based
      intervention for improving the inpatient management of fever, hyperglycemia, and
      swallowing dysfunction in the first three-days following stroke improved outcomes
      at 90 days by 15%. We designed a quantitative process evaluation to further
      explain and illuminate this finding. METHODS: Blinded retrospective medical
      record audits were undertaken for patients from 19 stroke units prior to and
      following the implementation of three multidisciplinary evidence-based protocols
      (supported by team-building workshops, and site-based education and support) for
      the management of fever (temperature >=37.5 degrees C), hyperglycemia (glucose
      >11 mmol/l), and swallowing dysfunction in intervention stroke units. RESULTS:
      Data from 1804 patients (718 preintervention; 1086 postintervention) showed that
      significantly more patients admitted to hospitals allocated to the intervention
      group received care according to the fever (n = 186 of 603, 31% vs. n = 74 of
      483, 15%, P < 0.001), hyperglycemia (n = 22 of 603, 3.7% vs. n = 3 of 483, 0.6%,
      P = 0.01), and swallowing dysfunction protocols (n = 241 of 603, 40% vs. n = 19
      of 483, 4.0%, P <= 0.001). Significantly more patients in these intervention
      stroke units received four-hourly temperature monitoring (n = 222 of 603, 37% vs.
      n = 90 of 483, 19%, P < 0.001) and six-hourly glucose monitoring (194 of 603, 32%
      vs. 46 of 483, 9.5%, P < 0.001) within 72 hours of admission to a stroke unit,
      and a swallowing screen (242 of 522, 46% vs. 24 of 350, 6.8%, P <= 0.0001) within
      the first 24 hours of admission to hospital. There was no difference between the
      groups in the treatment of patients with fever with paracetamol (22 of 105, 21%
      vs. 38 of 131, 29%, P = 0.78) or their hyperglycemia with insulin (40 of 100, 40%
      vs. 17 of 57, 30%, P = 0.49). INTERPRETATION: Our intervention resulted in better
      protocol adherence in intervention stroke units, which explains our main trial
      findings of improved patient 90-day outcomes. Although monitoring practices
      significantly improved, there was no difference between the groups in the
      treatment of fever and hyperglycemia following acute stroke. A significant link
      between improved treatment practices and improved outcomes would have explained
      further the success of our intervention, and we are still unable to explain
      definitively the large improvements in death and dependency found in the main
      trial results. One potential explanation is that improved monitoring may have led
      to better overall surveillance of deteriorating patients and faster initiation of
      treatments not measured as part of the main trial.

PMID- 24289457
TI  - Niche filtering rather than partitioning shapes the structure of temperate forest
      ant communities.
AB  - An ever-increasing number of studies use tools from community phylogenetics to
      infer the processes underlying the assembly of communities. However, very few
      studies simultaneously use experimental approaches to characterize the ecological
      niches of species and directly assess the importance of these structuring
      processes. In this study, we developed an experimental approach for quantifying
      the use of four types of food resources and three habitat templets in temperate
      forest ant assemblages. We then used null models to assess whether niches
      overlapped more or less than expected by chance. Finally, we integrated
      comparative phylogenetic methods with experimental data on niche use to assess
      the degree of phylogenetic signal in several key components of the niche. We
      found that niche filtering, rather than partitioning, was the predominant
      structuring force. Niche filtering resulted from conservatism in habitat niches
      in evolutionary time and limitations in the availability of food resources in
      ecological time. Our study thus supports the idea that similarities in niches
      among species, rather than the differences, drive the assembly of ant
      communities. 

PMID- 24289458
TI  - Neglected increases in rural road traffic mortality in China: findings based on
      health data from 2005 to 2010.
AB  - BACKGROUND: Recent changes in rural road traffic mortality have not been examined
      in China although rural residents were reported as having greater risk of road
      traffic injury than urban residents. We aimed to examine changes in urban and
      rural road traffic mortality rates between 2005 and 2010 in China. METHODS:
      Mortality rates came from the publicly available health data of the Ministry of
      Health-Vital Registration System that is based on a national representative
      sample (about 10% of total population), including 41 surveillance points in urban
      areas (15 large cities and 21 middle/small cities) and 85 surveillance points in
      rural areas. The causes of deaths were coded using the Tenth International
      Classification of Diseases (ICD-10). Linear regression was used to test the
      statistical significance of changes in mortality rates. We calculated the percent
      change in rates to quantify the change between 2005 and 2010, which was
      calculated as regression coefficient * 100 * 5 divided by the rate in 2005.
      RESULTS: In rural areas, road traffic mortality increased by 70%, changing from
      13.3 per 100,000 population in 2005 to 22.7 per 100,000 population in 2010. In
      contrast, the road traffic mortality merely increased by 4% in the study time
      period, rising from 13.1 to 13.9 per 100,000 population in urban areas. Both the
      increases in road traffic mortality from motor vehicle crashes and from non-motor
      vehicle crashes were larger in rural areas than in urban areas (106% vs. 4%; 29%
      vs. 3%). CONCLUSION: The tremendous increase in road traffic mortality in rural
      areas calls for urgent actions to reduce road traffic injuries to motor vehicle
      occupants, motorcyclists, bicyclists and pedestrians in in rural areas.

PMID- 24289459
TI  - Undergraduate medical education in general practice/family medicine throughout
      Europe - a descriptive study.
AB  - BACKGROUND: It is increasingly becoming evident that a strong primary health care
      system is more likely to provide better population health, more equity in health
      throughout the population, and better use of economic resources, compared to
      systems that are oriented towards specialty care. Developing and maintaining a
      strong and sustainable primary health care requires that a substantial part of
      graduating doctors go into primary care. This in turn requires that general
      practice/family medicine (GP/FM) strongly influences the curricula in medical
      schools. In the present paper we aim at describing the extent of GP/FM teaching
      in medical schools throughout Europe, checking for the presence of GP/FM
      curricula and clinical teaching in GP offices. METHODS: A brief questionnaire was
      e-mailed to GP/FM or other professors at European medical universities. RESULTS:
      259 out of 400 existing universities in 39 European countries responded to our
      questionnaire. Out of these, 35 (13.5%) reported to have no GP/FM curriculum.
      These 35 medical faculties were located in 12 different European countries. In
      addition, 15 of the medical schools where a GP/FM curriculum did exist, reported
      that this curriculum did not include any clinical component (n = 5), or that the
      clinical part of the course was very brief - less than one week, mostly only a
      few hours (n = 10). In total, 50 universities (19%) thus had no or a very brief
      GP/FM curriculum. These were mainly located in the Eastern or Southern European
      regions. CONCLUSION: It is still possible to graduate from European medical
      universities without having been exposed to a GP/FM curriculum. The European
      Academy of Teachers in General Practice (EURACT) will launch efforts to change
      this situation.

PMID- 24289460
TI  - Clinical utility of the functional independence measure for assessment of
      patients with Alzheimer's disease and vascular dementia.
AB  - AIM: The aim of this study was to investigate the clinical utility of the
      Functional Independence Measure (FIM), and especially FIM-Cognition (FIM-C)
      scores, in patients with Alzheimer's disease (AD) and vascular dementia (VaD),
      and to determine the influence of behavioural and psychological symptoms of
      dementia (BPSD) on FIM-C scores. METHODS: This was a cross-sectional survey of 37
      AD and 40 VaD patients. Cognitive function was assessed with the Cognitive
      Abilities Screening Instrument. Activities of daily living were evaluated with
      the FIM and the Barthel Index. BPSD were assessed with the Behavioural Pathology
      in Alzheimer's Disease Frequency Weighted Severity Scale. RESULTS: For both
      groups, Spearman's correlations were found between FIM-Motor and Barthel Index
      scores and between FIM-C and Mini Mental State Examination scores. Each FIM-C
      subscore was correlated with Cognitive Abilities Screening Instrument scores in
      both groups, except for the FIM-C Social interaction subscore in VaD. VaD
      patients showing Activity Disturbance and Aggressiveness on the Behavioural
      Pathology in Alzheimer's Disease Frequency Weighted Severity Scale had
      significantly lower FIM-C Memory and Social interaction subscores than those
      without BPSD. CONCLUSION: The results suggest that the FIM-Motor and FIM-C scales
      are useful measures of physical and cognitive disabilities in patients with AD
      and VaD. The FIM-C profile of AD may reflect global cognitive function, while
      that of VaD may be more influenced by BPSD.

PMID- 24289461
TI  - Brain-derived neurotrophic factor Val66Met polymorphism and cognitive function in
      persons with cardiovascular disease.
AB  - AIM: Cognitive impairment is common among persons with cardiovascular disease
      (CVD), and several potential aetiological mechanisms have been described,
      including contributions of genetic markers such as variations in the brain
      derived neurotrophic (BDNF) gene. This current study examined the associations of
      BDNF genotype with cognitive function among individuals with CVD. METHODS: This
      study included 110 participants with CVD who completed a comprehensive
      neuropsychological battery that assessed global cognitive function,
      attention/executive function, memory, language, and visuospatial abilities. All
      participants also underwent blood draw to provide a DNA sample that was used to
      determine BDNF genotype. Carriers of either one or two copies of the methionine
      allele of BDNF were categorized into one group (n = 33); non-carriers were
      categorized into a second group (n = 77). RESULTS: After adjustment for
      demographic and medical characteristics, hierarchical regression analyses
      revealed persons with one or more methionine alleles displayed better performance
      than valine/valine individuals for attention/executive function (beta = 0.22, P =
      0.047) and memory (beta = 0.25, P = 0.03), as well as a trend for language (beta
      = 0.19, P = 0.08) and visuospatial abilities (beta = 0.21, P = 0.06).
      CONCLUSIONS: BDNF Val66Met had little impact on cognitive functioning in a sample
      of older adults with CVD, and significant findings contradicted that predicted by
      past work. Future work is much needed to clarify the mechanisms of these
      findings, particularly studies examining both circulating BDNF levels and genetic
      variation in the BDNF gene and cognitive function over time.

PMID- 24289462
TI  - Daytime sleepiness: a risk factor for poor social engagement among the elderly.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      social engagement and daytime sleepiness among aged residents of a veterans'
      housing facility in Taiwan. METHODS: A total of 597 men were enrolled in this
      cross-sectional study. Each subject was assessed with the Resident Assessment
      Instrument-Minimum Data Set, Geriatric Depression Scale, Pittsburgh Sleep Quality
      Index, and Mini-Mental State Examination. Social engagement was measured with the
      Index of Social Engagement (ISE), and daytime sleepiness was defined according to
      the relevant Pittsburgh Sleep Quality Index subcomponent. Subjects were divided
      into two groups according to their ISE levels. A multivariate logistic regression
      model was used to examine the association between ISE and other variables.
      RESULTS: The sample's mean age was 80.8 +/- 5.0 years (range: 65-99 years). Mean
      ISE score was 1.5 +/- 1.3 (range 0-5), with 52% of participants reporting poor
      social engagement (ISE = 0-1). Mean Pittsburgh Sleep Quality Index global score
      was 5.6 +/- 3.6 (range: 0-18), and 31% of participants reported daytime
      sleepiness. The analysis was adjusted for level of depression, cognitive
      impairment, dependence in activities of daily life, unsettled relationships, and
      illiteracy. After adjustment, daytime sleepiness was found to be independently
      associated with subjects' level of social engagement (odds ratio: 2.5; 95%
      confidence interval: 1.7-3.8; P < 0.001). CONCLUSIONS: Daytime sleepiness and
      poor social engagement are common among aged residents of a veterans' housing
      facility. Subjects experiencing daytime sleepiness but not poor general sleep
      quality were at increased risk of poor social engagement. The clinical care of
      older residents must focus on improving daytime sleepiness to enhance their
      social engagement.

PMID- 24289464
TI  - Mental illness and a high-risk, elderly Japanese population: characteristic
      differences related to gender and residential location.
AB  - PURPOSE: Examining the sociodemographic determinants of psychological distress is
      important in identifying specific subgroups in need of further intervention.
      However, there are few studies focusing on older populations and on the role of
      gender or location of residence. To try to clarify characteristics of a
      population at high risk for mental illness, we examined the sociodemographic
      determinants of psychological distress in older adults living in three different
      locations. METHODS: A mail survey was used to collect data on levels of
      psychological distress and sociodemographic characteristics from a population
      based sample of 1894 older adults who lived in Bunkyo (urban setting), Fuchu
      (suburban setting) and Oyama (rural setting) in Japan (aged 65-74 years, 51.3%
      men). Psychological distress level was measured based on Kessler's six-item
      psychological distress scale (K6) and dichotomized into two groups with a cut-off
      score of 5 (0-4 or 5-24). Multiple logistic regression analyses were used to
      examine the associations between sociodemographic factors, specifically gender
      and location of residence, and psychological distress levels. RESULTS: The
      variables of older age, living in Bunkyo, living in Oyama and living alone were
      significantly associated with high psychological distress. Although these
      associations were observed in men, no associations were observed in women.
      Location-specific analyses showed significant associations between
      sociodemographic and psychological distress among men living in Oyama, but not
      among those in Bunkyo or Fuchu. CONCLUSIONS: Sociodemographic factors were
      significantly correlated with psychological distress, particularly among older
      men in rural areas. Characteristics of a population at high risk for mental
      illness may vary based on gender and location of residence. Health promotion
      initiatives for older adults may be more effective if they take these demographic
      factors into account.

PMID- 24289463
TI  - Stressful life events and neuroticism as predictors of late-life versus early
      life depression.
AB  - BACKGROUND: The occurrence of depression in younger adults is related to the
      combination of long-standing factors such as personality traits (neuroticism) and
      more acute factors such as the subjective impact of stressful life events.
      Whether an increase in physical illnesses changes these associations in old age
      depression remains a matter of debate. METHODS: We compared 79 outpatients with
      major depression and 102 never-depressed controls; subjects included both young
      (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included
      the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative
      Illness Rating Scale. Logistic regression models analyzed the association between
      depression and subjective impact of stressful life events while controlling for
      neuroticism and physical illness. RESULTS: Patients and controls experienced the
      same number of stressful life events in the past 12 months. However, in contrast
      to the controls, patients associated the events with a subjective negative
      emotional impact. Negative stress impact and levels of neuroticism, but not
      physical illness, significantly predicted depression in young age. In old age,
      negative stress impact was weakly associated with depression. In this age group,
      depressive illness was also determined by physical illness burden and
      neuroticism. CONCLUSIONS: Our data suggest that the subjective impact of life
      stressors, although rated as of the same magnitude, plays a less important role
      in accounting for depression in older age compared to young age. They also
      indicate an increasing weight of physical illness burden in the prediction of
      depression occurrence in old age.

PMID- 24289465
TI  - Clinical features of late-onset schizophrenia in Japan: comparison with early
      onset cases.
AB  - BACKGROUND: Although the fourth edition of the Diagnostic and Statistical Manual
      of Mental Disorders abandoned the use of the specifier 'late-onset', a
      considerable number of studies have reported clinical characteristics of late
      onset schizophrenia. Still, only limited research has been conducted on late
      onset schizophrenia, especially in Asian countries. In this epidemiological
      study, the clinical characteristics of late-onset schizophrenia were examined in
      comparison with early-onset schizophrenia. METHODS: All patients with
      schizophrenia admitted to the psychiatric ward of Jichi Medical University
      Hospital between 1 April 1993 and 31 March 2006 were divided into two groups
      according to age at first onset: >=40 years (late-onset group) and <40 years
      (early-onset group). The sex ratio, presence or absence of depression,
      schizophrenia subtype, premorbid character, marital history, and employment
      history at first onset were compared between the two groups. RESULTS: Of the 316
      patients with schizophrenia identified, 38 patients were assigned to the late
      onset group and 278 patients to the early-onset group. Mean age at onset was 23.9
      +/- 8.2 years for all men and 28.0 +/- 13.5 years for all women. The late-onset
      group was characterized by more women, more paranoid type, more depressive
      symptoms, less introverted premorbid character, better premorbid adaptation and
      less neuroleptics. CONCLUSION: The characteristics of late-onset schizophrenia in
      Japan are in line those reported previously.

PMID- 24289466
TI  - Levodopa treatment and mood fluctuation in dementia with Lewy bodies: a case
      report.
AB  - L-3,4-dihydroxyphenylalanine (L-dopa) has been the gold standard for
      pharmacotherapy for parkinsonism in patients with dementia with Lewy bodies
      (DLB). While L-dopa treatment is related to visual hallucinations, its
      relationship to mood fluctuation in DLB is poorly understood. Herein, we report
      the improvement of behavioural and psychological symptoms of dementia through the
      adjustment of L-dopa treatment in a 78-year-old woman with probable DLB. Her
      marked mood swings were improved by changing L-dopa administration from three to
      five times per day while maintaining the same total daily dosage. This
      observation suggests that there may be an association between plasmatic L-dopa
      levels and mood fluctuation in patients with DLB. This pharmacological approach
      may be useful in the management of behavioural and psychological symptoms of
      dementia without the use of antipsychotic agents to avoid severe neuroleptic
      sensitivity, which is one of the suggestive clinical features in the Third
      Consortium on DLB clinical criteria. 

PMID- 24289467
TI  - Senile onset frontotemporal lobar degeneration with TAR-DNA binding protein 43
      proteinopathy primarily presenting with wasteful habits.
AB  - We present an autopsied case of a senile Japanese woman with sporadic
      frontotemporal lobar degeneration (FTLD) presenting as frontotemporal dementia.
      Disease onset was at the age of 70 and presented as a behaviour disorder,
      particularly involving wasteful habits. The patient had repeated incidents of
      making expensive purchases and then had difficulty making payments. Following
      these symptoms, she showed other changes of character such as lethargy and
      apathy. She gradually showed signs of parkinsonism including rigidity and
      bradykinesia, and in the terminal stage, an akinetic mutism state with
      quadriplegia in flexion was observed. Head magnetic resonance imaging revealed
      severe frontotemporal lobe atrophy with severe lateral ventricular dilatation and
      frontal white matter degeneration. At autopsy, the brain weighed 930 g and the
      frontotemporal cerebral cortex showed neuron loss with gliosis, tissue
      rarefaction and spongiform change, particularly in the superficial layers.
      Pathologic degeneration was more severe in the anterior portion of the frontal
      lobe with extensive white matter degeneration. Immunostaining for phosphorylated
      TAR-DNA binding protein 43 (TDP-43) revealed numerous neuronal cytoplasmic
      inclusions and extensive short dystrophic neuritis, particularly in the
      frontotemporal cortex. Many TDP-43-positive cytoplasmic inclusions were also
      observed in the dentate gyrus of the hippocampus. The patient was pathologically
      diagnosed with FTLD with TDP-43-positive inclusions (FTLD-TDP) without motor
      neuron disease. The immunohistochemical findings corresponded to type A of the
      FTLD-TDP pathology classification system. 

PMID- 24289468
TI  - Predicting drug-target interactions using probabilistic matrix factorization.
AB  - Quantitative analysis of known drug-target interactions emerged in recent years
      as a useful approach for drug repurposing and assessing side effects. In the
      present study, we present a method that uses probabilistic matrix factorization
      (PMF) for this purpose, which is particularly useful for analyzing large
      interaction networks. DrugBank drugs clustered based on PMF latent variables show
      phenotypic similarity even in the absence of 3D shape similarity. Benchmarking
      computations show that the method outperforms those recently introduced provided
      that the input data set of known interactions is sufficiently large--which is the
      case for enzymes and ion channels, but not for G-protein coupled receptors
      (GPCRs) and nuclear receptors. Runs performed on DrugBank after hiding 70% of
      known interactions show that, on average, 88 of the top 100 predictions hit the
      hidden interactions. De novo predictions permit us to identify new potential
      interactions. Drug-target pairs implicated in neurobiological disorders are
      overrepresented among de novo predictions.

PMID- 24289469
TI  - Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow
      transplantation correlate with failure of engraftment.
AB  - BACKGROUND: The development of genetically modified pigs, which lack the
      expression of alpha 1-3 galactosyl transferase, (GalT-KO pigs) has facilitated
      the xenogeneic transplantation of porcine organs and tissues into primates by
      avoiding hyperacute rejection due to pre-existing antibodies against the Gal
      epitope. However, antibodies against other antigens (anti-non-Gal antibodies),
      are found at varying levels in the pre-transplant sera of most primates. We have
      previously found that baboons with high levels of pre-transplant anti-non-Gal
      IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft
      following pig-to-baboon bone marrow transplantation (Xenotransplantation, 17,
      2010 and 300). Two baboons with low levels of pre-transplant anti-non-Gal IgG,
      conditioned with the same regimen, showed porcine bone marrow progenitors at 28
      days following transplantation, suggesting engraftment. These baboons also showed
      evidence of donor-specific hyporesponsiveness. This observation led us to
      investigate the hypothesis that selecting for baboon recipients with low pre
      transplant anti-non-Gal IgG levels might improve engraftment levels following
      GalT-KO pig-to-baboon bone marrow transplantation. METHODS: Five baboons, with
      low pre-transplant anti-non-Gal IgG levels, received transplantation of bone
      marrow cells (1-5 * 10(9) /kg of recipient weight) from GalT-KO pigs. They
      received a non-myeloablative conditioning regimen consisting of low-dose total
      body irradiation (TBI) (150 cGy), thymic irradiation (700 cGy), anti-thymocyte
      globulin (ATG), and tacrolimus. In addition, two baboons received Rituximab and
      Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using
      GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR
      on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal
      antibody levels were assessed by serum binding toward GalT-KO PBMC using flow
      cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and
      baboon-specific antibodies and baboon anti-pig cellular responses were assessed
      by mixed lymphocyte reactions (MLR). RESULTS: As previously reported, two of five
      baboons demonstrated detectable bone marrow engraftment at 4 weeks after
      transplantation. Engraftment was associated with lack of an increase in anti-non
      Gal IgG levels as well as cellular hyporesponsiveness toward pig. Three
      subsequent baboons with similarly low levels of pre-existing anti-non-Gal IgG
      showed no engraftment and an increase in anti-non-Gal IgG antibody levels
      following transplantation. Peripheral macrochimerism was only seen for a few days
      following transplantation regardless of antibody development. CONCLUSIONS:
      Selecting for baboon recipients with low levels of pre-transplant anti-non-Gal
      IgG did not ensure bone marrow engraftment. Failure to engraft was associated
      with an increase in anti-non-Gal IgG levels following transplantation. These
      results suggest that anti-non-Gal-IgG is likely involved in early bone marrow
      rejection and that successful strategies for combating anti-non-Gal IgG
      development may allow better engraftment. Since engraftment was only low and
      transient regardless of antibody development, innate immune, or species
      compatibility mechanisms will likely also need to be addressed to achieve long
      term engraftment.

PMID- 24289471
TI  - Xenotransplantation literature update, September-October 2013.

PMID- 24289470
TI  - Human cytokines activate JAK-STAT signaling pathway in porcine ocular tissue.
AB  - BACKGROUND: The JAK/STAT (Janus Tyrosine Kinase, Signal Transducers and
      Activators of Transcription) pathway is associated with cytokine or growth factor
      receptors and it is critical for growth control, developmental regulation and
      homeostasis. The use of porcine ocular cells as putative xenotransplants appears
      theoretically possible. The aim of this study was to investigate the response of
      various porcine ocular cells in vitro to human cytokines in regard to the
      activation of JAK-STAT signaling pathways. METHODS: Porcine lens epithelial
      cells, pigmented iris epithelial cells and pigmented ciliary body cells were used
      in this study. These cells were isolated from freshly enucleated porcine eyes by
      enzymatic digestion. Cultured cells between passages 3-8 were used in all
      experiments. Electromobility shift assay (EMSA), proliferation assay,
      immunofluorescence staining and flow cytometry were used to evaluate the JAK-STAT
      signaling pathway in these cells. RESULTS: JAK/STAT signaling pathways could be
      activated in porcine pigmented epithelial ciliary body cells, in pigmented iris
      epithelial cells and in lens epithelial cells in response to porcine and human
      interferons and cytokines. All cells showed very strong STAT1 activation upon
      stimulation with porcine interferon-gamma. Porcine ocular cells also respond to
      human cytokines; IFN-alpha induced strong activation of STAT1 in EMSA, flow
      cytometry and immunofluorescence experiments whereas activation of STAT3 was less
      strong in EMSA, but strong in flow cytometry and immunofluorescence. Human
      recombinant IL-6 activated STAT3 and human IL-4 activated STAT6. With the help of
      immunofluorescence assay and flow cytometry we observed nuclear localization of
      STAT proteins after activation of porcine ocular cells with cytokines and
      interferons. Human IFN-alpha had an inhibitory effect on porcine ocular cells in
      proliferation assays. CONCLUSION: Our study demonstrated that some types of human
      cytokines and interferon activate intracellular JAK-STAT signaling pathways in
      porcine ocular cells. We hypothesize that direct stimulation of the JAK-STAT
      pathway in porcine cells in response to human cytokines will lead to
      complications or failure, if pig-to-human ocular tissue xenotransplantation were
      to be carried out. For successful xenotransplantation among other obstacles there
      must be new approaches developed to regulate signaling pathways.

PMID- 24289472
TI  - The clinicopathological significance and relationship of Gli1, MDM2 and p53
      expression in resectable pancreatic cancer.
AB  - AIMS: To study the expression of Gli1, MDM2 and p53 for clinical significance in
      pancreatic cancer (PC), and their functional relationship in regulating the
      biological behaviour of PC cells. METHODS AND RESULTS: Immunohistochemistry
      showed that the expression of Gli1, MDM2 and p53 was much higher in 57 cases of
      PC than in paired normal pancreatic tissues, and was positively associated with
      tumour UICC stage and T stage (P < 0.05). Patients with expression of Gli1 only
      or coexpression of Gli1 and MDM2 had significantly worse overall survival than
      patients with negative expression (P < 0.05). RNA interference showed that p53
      knockdown increased the protein level of Gli1 but decreased the level of MDM2,
      and enhanced cell invasion and migration in wild-type p53 Capan-2 cells; whereas
      Gli1 or MDM2 knockdown did not change p53 expression, but decreased the protein
      level of MDM2 or Gli1, respectively, and inhibited cell invasion and migration in
      mutant p53 PANC-1 cells. CONCLUSIONS: Overexpression of Gli1, MDM2 and mutant p53
      contributes to the development and progression of PC, and plays an important role
      in predicting PC patients' prognosis. Moreover, we report a positive association
      between Gli1 and MDM2 in PC cells, but their relationship with p53 is dependent
      on wild-type or mutant p53 status.

PMID- 24289473
TI  - A survey of preventive measures used and their impact on central line-associated
      bloodstream infections (CLABSI) in intensive care units (SPIN-BACC).
AB  - BACKGROUND: The Quebec central line-associated bloodstream infections (CLABSI) in
      intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates
      in most ICUs. Given the surveillance trends observed in recent years, we aimed to
      determine what preventive measures have been implemented, if compliance to
      measures was monitored and its impact on CLABSI incidence rates. METHODS: All
      hospitals participating in the Quebec healthcare-associated infections
      surveillance program (SPIN-BACC - n = 48) received a 77-question survey about
      preventive measures implemented and monitored in their ICU. The questionnaire was
      validated for construct, content, face validity, and reliability. We used Poisson
      regression to measure the association between compliance monitoring to preventive
      measures and CLABSI rates. RESULTS: Forty-two (88%) eligible hospitals completed
      the survey. Two components from the maximum barrier precautions were used less
      optimally: cap (88%) and full sterile body drape (71%). Preventive measures
      reported included daily review of catheter need (79%) and evaluation of insertion
      site for the presence of inflammation (90%). Two hospitals rewired lines even if
      an infection was suspected or documented.In adult ICUs, there was a statistically
      significant greater decrease in CLABSI rates in ICUs that monitored compliance to
      preventive insertion measures, after adjusting for teaching status and the number
      of hospital beds (p = 0.036). CONCLUSIONS: Hospitals participating to the SPIN
      BACC program follow recommendations for CLABSI prevention, but only a minority
      locally monitor their application. Compliance monitoring of preventive measures
      for catheter insertion was associated with a decrease in CLABSI incidence rates.

PMID- 24289475
TI  - Cross-Cultural Psychometric Assessment of the Leeds Assessment of Neuropathic
      Symptoms and Signs (LANSS) Pain Scale in the Portuguese Population.
AB  - BACKGROUND: Chronic pain is a well-known phenomenon. The differential diagnosis
      between neuropathic and nociceptive pain syndromes is a challenge. Consequently,
      assessment instruments that can distinguish between these conditions in a
      standardized way are of the utmost importance. The Leeds Assessment of
      Neuropathic Symptoms and Signs (LANSS) is a screening tool developed to identify
      chronic neuropathic pain. The aim of this study was the Portuguese language
      translation, linguistic adaptation of the LANSS pain scale, its semantic
      validation, internal consistency, temporal stability, as well its validity and
      discriminative power. METHODS: LANSS Portuguese version scale was applied to 165
      consecutive patients attending the pain clinic: 103 fulfilled the clinical
      criteria for the diagnosis of pain of neuropathic origin and the remaining 62
      fulfilled the criteria for nociceptive pain. RESULTS: The scale proved to be an
      internally consistent (Cronbach's alpha = 0.78) and reliable instrument with good
      test-retest stability (r = 0.7; P < 0.001). However, its validity and specificity
      with a cutoff point of >= 12, for differentiating patients with neuropathic pain
      from those with non-neuropathic pain, had 89% sensitivity, 74% specificity,
      positive predictive value of 85%, and negative predictive value of 81%.
      CONCLUSIONS: The Portuguese LANSS version pain scale properties lead us to the
      conclusion that such a cross-cultural version is a reliable and valid instrument
      for the differentiation of this type of pain. Its usage is recommended.

PMID- 24289474
TI  - Analysis of porcine adipose tissue transcriptome reveals differences in de novo
      fatty acid synthesis in pigs with divergent muscle fatty acid composition.
AB  - BACKGROUND: In pigs, adipose tissue is one of the principal organs involved in
      the regulation of lipid metabolism. It is particularly involved in the overall
      fatty acid synthesis with consequences in other lipid-target organs such as
      muscles and the liver. With this in mind, we have used massive, parallel high
      throughput sequencing technologies to characterize the porcine adipose tissue
      transcriptome architecture in six Iberian x Landrace crossbred pigs showing
      extreme phenotypes for intramuscular fatty acid composition (three per group).
      RESULTS: High-throughput RNA sequencing was used to generate a whole
      characterization of adipose tissue (backfat) transcriptome. A total of 4,130
      putative unannotated protein-coding sequences were identified in the 20% of reads
      which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were
      represented by interspersed repeats, SINEs being the most abundant elements.
      Differential expression analyses identified 396 candidate genes among divergent
      animals for intramuscular fatty acid composition. Sixty-two percent of these
      genes (247/396) presented higher expression in the group of pigs with higher
      content of intramuscular SFA and MUFA, while the remaining 149 showed higher
      expression in the group with higher content of PUFA. Pathway analysis related
      these genes to biological functions and canonical pathways controlling lipid and
      fatty acid metabolisms. In concordance with the phenotypic classification of
      animals, the major metabolic pathway differentially modulated between groups was
      de novo lipogenesis, the group with more PUFA being the one that showed lower
      expression of lipogenic genes. CONCLUSIONS: These results will help in the
      identification of genetic variants at loci that affect fatty acid composition
      traits. The implications of these results range from the improvement of porcine
      meat quality traits to the application of the pig as an animal model of human
      metabolic diseases.

PMID- 24289476
TI  - Competitive Fe(II)-Zn(II) uptake on a synthetic montmorillonite.
AB  - The interaction of Fe(II) with clay minerals is of particular relevance in global
      geochemical processes controlling metal and nutrient cycles and the fate of
      contaminants. In this context, the influence of competitive sorption effects
      between Fe(II) and other relevant transition metals on their uptake
      characteristics and mobility remains an important issue. Macroscopic sorption
      experiments combined with surface complexation modeling and extended X-ray
      absorption fine structure (EXAFS) spectroscopy were applied to elucidate
      competitive sorption processes between divalent Fe and Zn at the clay mineral
      water interface. Sorption isotherms were measured on a synthetic iron-free
      montmorillonite (IFM) under anoxic conditions (O2 <0.1 ppm) for the combinations
      of Zn(II)/Fe(II) and Fe(II)/Zn(II), where the former metal in each pair
      represents the trace metal (<10(-7) M) and the latter the competing metal at
      higher concentrations (10(-7) to 10(-3) M). Results of the batch sorption and
      EXAFS measurements indicated that Fe(II) is competing with trace Zn(II) for the
      same type of strong sites if Fe(II) is present in excess, whereas no competition
      between trace Fe(II) and Zn(II) was observed if Zn(II) is present at high
      concentrations. The noncompetitive behavior suggests the existence of sorption
      sites which have a higher affinity for Fe(III), where surface-induced oxidation
      of the sorbed Fe(II) to Fe(III) occurred, and which are not accessible for
      Zn(II). The understanding of this competitive uptake mechanism between Fe(II) and
      Zn(II) is of great importance to assess the bioavailability and mobility of
      transition metals in the natural environment. 

PMID- 24289477
TI  - Brain metastasis from hepatocellular carcinoma: the role of surgery as a
      prognostic factor.
AB  - BACKGROUND: The incidence of brain metastasis from hepatocellular carcinoma (HCC)
      is expected to increase as a result of prolonged survival due to the recent
      advances in HCC treatment. However, there is no definite treatment strategy for
      brain metastasis from HCC mainly due to its rarity and dismal prognosis. To
      provide helpful recommendations in treatment of brain metastasis from HCC, the
      authors aimed to identify prognostic factors that influence survival rates with a
      review of the recently published data. METHODS: Thirty-three cases of brain
      metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC
      patients and reviewed retrospectively in terms of clinical and radiological
      features. RESULTS: Median overall survival time after diagnosis of brain
      metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-,
      6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival
      of the patients treated with surgical resection or surgical resection followed by
      whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was
      longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or
      GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of
      patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p<0.001).
      Child-Pugh's classification A group had a longer median survival time than Child
      Pugh's classification B or C group (14.4 weeks vs 8.4 weeks, p=0.038). RPA class
      I & II group had also a longer median survival time than RPA class III group did
      (13.4 weeks vs 2.4 weeks, p=0.001). Surgical resection (hazard ratio [HR] 0.23,
      95% CI 0.08-0.66, p=0.006) and good liver function at the time of brain
      metastasis (HR 0.25, 95% CI 0.09-0.69, p=0.007) were found to be the powerful
      prognostic factors for favorable survival in the multivariate analysis. In
      addition, presence of intratumoral hemorrhage was a statistically significant
      prognostic factor for survival. CONCLUSION: Although HCC patients with brain
      metastasis showed a very dismal prognosis, surgical intervention was shown to
      lead to relative prolongation of the survival time, especially in those with
      preserved hepatic function.

PMID- 24289478
TI  - Getting to the heart of intraflagellar transport using Trypanosoma and
      Chlamydomonas models: the strength is in their differences.
AB  - Cilia and flagella perform diverse roles in motility and sensory perception, and
      defects in their construction or their function are responsible for human genetic
      diseases termed ciliopathies. Cilia and flagella construction relies on
      intraflagellar transport (IFT), the bi-directional movement of 'trains' composed
      of protein complexes found between axoneme microtubules and the flagellum
      membrane. Although extensive information about IFT components and their mode of
      action were discovered in the green algae Chlamydomonas reinhardtii, other model
      organisms have revealed further insights about IFT. This is the case of
      Trypanosoma brucei, a flagellated protist responsible for sleeping sickness that
      is turning out to be an emerging model for studying IFT. In this article, we
      review different aspects of IFT, based on studies of Chlamydomonas and
      Trypanosoma. Data available from both models are examined to ask challenging
      questions about IFT such as the initiation of flagellum construction, the setting
      up of IFT and the mode of formation of IFT trains, and their remodeling at the
      tip as well as their recycling at the base. Another outstanding question is the
      individual role played by the multiple IFT proteins. The use of different models,
      bringing their specific biological and experimental advantages, will be
      invaluable in order to obtain a global understanding of IFT. 

PMID- 24289480
TI  - [Fluorescence in situ hybridization on histologic sections].
AB  - I-FISH (fluorescence in situ hybridization on interphasic nuclei) represents a
      laboratory method linking morphological investigations (histological sections of
      formaldehyde fixed and paraffin embedded tissues) with molecular techniques
      (sequence specificity of nucleic acids bases for a certain locus). I-FISH is
      relatively undemanding for a laboratory workout, but offering a lot of important
      information about the investigated cells. Within a scope of pathology departments
      I-FISH is utilized mostly in diagnostics of neoplasms. I-FISH is helpful in
      detecting gene copy numbers (amplifications or deletions), and, importantly, in
      establishing copy numbers of individual chromosomes (polysomies or monosomies),
      chromosomal breaks and translocations. At present, I-FISH is used not only for
      diagnosis and estimation of prognosis, but also as a method to qualify a patient
      for a targeted biological therapy. Because demands on investigation of solid
      tumors keep raising I-FISH becomes a part of routine investigations. The aim of
      this paper is to summarize principles and the utility of I-FISH and to help the
      interested readers in finding a basic orientation in this laboratory method.

PMID- 24289481
TI  - [Laser capture microdissection and its practical applications].
AB  - Laser capture microdissection is a relatively young method used both in
      biomedical sciences as in other studies of animal and vegetable tissues and
      cells. Current human medicine and its methods of investigation are based on both
      current established processes, and simultaneously there are new experimental
      approaches from molecular biology tested. In this context it is highly desirable
      that the studied tissue is homogenous and representative population of cells. For
      this purposes at the late 80s the method of laser capture microdissection (LCM)
      has been developed, the first publication dealing with this method was released
      even in 1996. In current databases of literature we are able to find hundreds of
      papers focused on LCM such a method or as a part of methodic approach of
      experiments whose results led to the improved knowledge of genetic and proteomic
      nature of various diseases. This knowledge is of great promise for successful
      targeted therapy in the future.

PMID- 24289479
TI  - Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain
      inflammation via regulation of the function of microglia/macrophages after
      intracerebral hemorrhage in mice.
AB  - BACKGROUND: Microglia/macrophages are known to play important roles in initiating
      brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell
      immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical
      part in several inflammatory diseases through regulation of both adaptive and
      innate immune responses. Tim-3 can be expressed by microglia/macrophages and
      regulates their function in the innate immune response. However, the effect of
      Tim-3 on inflammatory responses following ICH is unclear. METHODS: In this study,
      we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and brain water
      content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days
      post-ICH in wild type (WT) ICH and Tim-3-/- ICH mice. The numbers of Tim-3
      positive cells,astrocytes, neutrophils and microglia/macrophages were detected
      using immunofluorescence staining. Cytokines were measured by ELISA. Double
      immunofluorescence labeling was performed to identify the cellular source of Tim
      3 expression. Mouse neurological deficit scores were assessed through animal
      behavior. RESULTS: Expression of Tim-3 increased early in mouse peri-hematomal
      brain tissue after autologous blood injection, peaked at day 1, and was
      positively correlated with the concentrations of TNF-alpha, IL-1beta, and brain
      water content. Tim-3 was predominantly expressed in microglia/macrophages.
      Compared with WT mice, Tim-3-/- mice had reduced ICH-induced brain inflammation
      with decreased TNF-alpha and IL-1beta, cerebral edema and neurological deficit
      scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The
      number of activated microglia/macrophages in Tim-3-/- ICH mice was much lower
      than that in WT ICH mice. CONCLUSIONS: Our findings demonstrate that Tim-3 plays
      an important role in brain inflammation after ICH, and may be a potential
      treatment target.

PMID- 24289482
TI  - [Immunophenotypization by means of flow cytometry in pathology].
AB  - Flow cytometry represents a modern analytical method useful for an assessment of
      selected cellular subpopulations in suspension (peripheral blood, aspirate of
      bone marrow, liquid fluid etc. and also in suspensions prepared from non-fixed
      solid tumors) in clinical and research laboratories. The method provides
      information on numerous surface or intracellular markers of the analyzed elements
      at the same time. The usage of fluorescent monoclonal antibodies against surface
      or intracellular antigens associated with specific type of cells (T-lymphocytes,
      B-lymphocytes etc.), with their developmental stage, or with monoclonality (for
      example antibodies against light chains of immunoglobulins), are the most
      valuable for the clinical practice. The most important application of flow
      cytometry in pathology has remained in hematologic malignancies, where this fast
      and exact method provides, practically in a real time, crucial information for
      correct diagnosis as well as for the choice of optimal therapy, and subsequently
      for assessing the effect of the therapy.

PMID- 24289483
TI  - [Minimal residual disease - detection possibilities in haematological and non
      haematological malignancies].
AB  - Minimal residual disease (MRD) monitoring is of a great importance for the
      patients and often determines their future therapy. At present, MRD detection in
      patients suffering from hematologic malignancies is included in most of treatment
      protocols. However, it appears that the MRD detection, sometimes described as
      circulating tumor cells or minimal disseminated disease, is important in patients
      with solid tumors as well. Molecular MRD monitoring principles include detection
      of specific DNA, RNA or protein markers of tumour cells, which are not present in
      bone marrow and/or peripheral blood cells. High specificity and sensitivity of
      this specific molecular tumour marker is necessary. Quantitative MRD monitoring
      by means of molecular methods can determine the decrease or increase of MRD
      level. In this review, we describe different molecular methods used, an overview
      on their advantages, limitations, and the sample quality and processing
      requirements. A summary of molecular markers employed in hematological and non
      hematological diseases is also presented.

PMID- 24289484
TI  - Mucinous carcinoma (non-intestinal type) arising in the ovarian mature cystic
      teratoma - a case report.
AB  - Somatic malignant transformation in mature cystic teratoma is a rare phenomenon
      of a malignancy of differentiated tissue structures of any stem line. The authors
      present a case of a 38-year-old female with mature cystic teratoma of both
      ovaries and with mucinous adenocarcinoma arising from endodermal germ line in the
      right ovary, showing immunohistochemical features of non-intestinal
      differentiation. At the time of diagnosis the tumour metastasized to the pelvic
      and retroperitoneal lymph nodes. The patient was treated with three lines of
      chemotherapy and died after 15 months with signs of massive progression into the
      retroperitoneal, mediastinal and cervical lymph nodes, retroperitoneum, duodenal
      wall and peritoneal cavity. Somatic malignant transformation in mature cystic
      teratoma is associated with poor prognosis. The most important prognostic factor
      is tumour stage at the time of diagnosis.

PMID- 24289485
TI  - Eosinophilic dysplasia of the cervix associated with HPV 6 infection - case
      report and review of the literature.
AB  - Eosinophilic dysplasia of the cervix is recently described unusual and somewhat
      obscure dysplastic lesion of squamous epithelium. We present histological
      features of a lesion in 41 years old woman. It was composed of cells with
      brightly eosinophilic cytoplasm contoured by a sharp and slightly broader
      cytoplasmic membrane, lacking maturation, with mild increase in nuclear
      cytoplasmic ratio, slight chromatin clumping and uneven mild nuclear clearing.
      Electronmicroscopic study showed mild crevices of the nuclear membrane in some
      dysplastic cells. Tissue in situ hybridization study confirmed the presence of
      HPV 6 in the form of patchy dotted pattern of integrated type.
      Immunohistochemistry revealed diffuse positive expression of antigen p16,
      extraordinarily in this case focally sparing basal part of the epithelium.
      Underestimation of this lesion can be avoided by paying attention to strong
      eosinophilia of the cytoplasm and sharp cellular contouring of the examined
      epithelium in routine hematoxylin-eosin staining.

PMID- 24289486
TI  - [How to improve the histopathological diagnosis of hepatocellular benign
      affections (adenoma versus focal nodular hyperplasia) in daily practice?].
AB  - Adenomas of the liver and focal nodular hyperplasia (FNH) are benign
      hepatocellular affection and their distinguishing in a needle biopsy sample and
      sometimes also in a surgical specimen causes often a problem. Although it might
      seem that the differentiation of the benign conditions is of a low value for the
      clinicians and also for the patients, the opposite is true. The risk of life
      threatening bleeding and risk of the malignant transformation of adenomas leads
      to request accurate diagnosis of these conditions. New genetic methods followed
      by immunohistochemical detection of several antigens enables more accurate
      distinction not only of the two main groups of FNH and adenomas, but allows also
      to distinguish subsets of adenomas with varying risk of malignant transformation.
      Therefore, to determine the subtype of adenoma represents now essential part of a
      biopsy diagnosis. Identification of the subsets of adenomas allows an
      individualized treatment with resection in high-risk forms and, on the other
      hand, allows avoiding liver resection in the case of small liver mass with a low
      risk of malignant transformation.

PMID- 24289487
TI  - Bridging the gap between research and practice in a clinical and training
      network: Aigle's program.
AB  - The aim of this article is to share our experience at the Aigle Foundation in
      fostering research that can conducted by (or in collaboration with) clinicians
      within a specific type of naturalistic setting-one that not only provides
      psychological services but also trains psychotherapists. After presenting the
      structure of Aigle and the implementation of its scientific-practitioner
      philosophy, we describe some of the research that has been conducted with our
      network of clinicians and the benefits of connecting clinical practice and
      academic work. We then discuss some of the obstacles that we have encountered in
      conducting such studies, as well as a number of strategies that we adopted in
      attempting to address these challenges. We end this article by briefly describing
      the current state of our practice-research network, and by offering some
      recommendations to facilitate the conduct of research by and for clinicians.

PMID- 24289488
TI  - Mapping the FACT-G cancer-specific quality of life instrument to the EQ-5D and SF
      6D.
AB  - OBJECTIVE: To help facilitate economic evaluations of oncology treatments, we
      mapped responses on cancer-specific instrument to generic preference-based
      measures. METHODS: Cancer patients (n = 367) completed one cancer-specific
      instrument, the FACT-G, and two preference-based measures, the EQ-5D and SF-6D.
      Responses were randomly divided to form development (n = 184) and cross
      validation (n = 183) samples. Relationships between the instruments were
      estimated using ordinary least squares (OLS), generalized linear models (GLM),
      and censored least absolute deviations (CLAD) regression approaches. The
      performance of each model was assessed in terms of how well the responses to the
      cancer-specific instrument predicted EQ-5D and SF-6D utilities using mean
      absolute error (MAE) and root mean squared error (RMSE). RESULTS: Physical,
      functional, and emotional well-being domain scores of the FACT-G best explained
      the EQ-5D and SF-6D. In terms of accuracy of prediction as measured in RMSE, the
      CLAD model performed best for the EQ-5D (RMSE = 0.095) whereas the GLM model
      performed best for the SF-6D (RMSE = 0.061). The GLM predicted SF-6D scores
      matched the observed values more closely than the CLAD and OLS. CONCLUSION: Our
      results demonstrate that the estimation of both EQ-5D and SF-6D utility indices
      using the FACT-G responses can be achieved. The CLAD model for the EQ-5D and the
      GLM model for the SF-6D are recommended. Thus, it is possible to estimate quality
      adjusted life years for economic evaluation from studies where only cancer
      specific instrument have been administered.

PMID- 24289489
TI  - Prevalence of gastrointestinal nematodes and Fasciola hepatica in sheep in the
      northwest of Spain: relation to climatic conditions and/or man-made environmental
      modifications.
AB  - BACKGROUND: In the present study we studied and updated the prevalence of the
      infections caused by gastrointestinal nematodes (GIN) and Fasciola hepatica in
      grazing sheep in the northwest (NW) of Spain for the last six years (2006-2011),
      and its relationship with the current climatic conditions. METHODS: We analyzed
      faecal samples from 110 flocks located in four different provinces of the
      Autonomous Community of Castilla y Leon: 76.4% of them were situated in Leon,
      12.7% in Zamora, 9.1% in Palencia and 1.8% in Valladolid. RESULTS: The prevalence
      of GIN was 100% and the mean of eggs per gram (epg) in faeces was 237.2 (+/-
      375.9) per flock. Regarding climatic conditions, we found a direct relationship
      between the GIN infection level and the maximum humidity (p<0.05) but inverse
      with the degree of solar radiation (p<0.05). The prevalence of fasciolosis was
      59.3%, with a mean epg of 17.5 (+/- 33.9) per flock; these values were correlated
      with the minimum humidity and precipitations (p<0.05). Comparing our results in
      Leon with previous studies during the early 1990s, the mean epg of GIN was
      increased slightly (134.3 epg); regarding fasciolosis, the prevalence rose
      significantly, from 26.7% to 60.5%. Since the 1990s we observed that the maximum
      temperature is nowadays 0.45 degrees C higher (17.0 degrees C) and the minimum
      0.5 degrees C lower (5.2 degrees C); the rainfall values were very similar in
      both decades but at the present time the humidity is higher (75.9%). CONCLUSIONS:
      We found that the prevalence of GIN and F. hepatica infections was directly
      influenced by the humidity and also by precipitations in the case of F. hepatica.
      Comparing the current prevalence with studies carried out in the same area for
      the early 1990s, we observed that nowadays the mean epg of GIN is higher with a
      possible cause being the differences in climatic conditions depending on the
      sampling year. Regarding F. hepatica infection, its prevalence rose significantly
      probably favoured by an increase in irrigated areas in the area of study.

PMID- 24289490
TI  - Comparison of tutored group with tutorless group in problem-based mixed learning
      sessions: a randomized cross-matched study.
AB  - BACKGROUND: Problem-based learning (PBL) involves discussions among students who
      resolve loosely-structured problems to facilitate learning. In the PBL
      curriculum, faculty tutors are employed as facilitators for small groups of
      students. Because of lack of time and staff shortage, the effectiveness of
      tutorless PBL has been discussed as an alternate option. METHODS: Sessions in
      which tutored and tutorless PBL groups are mixed were presented by 1st-year
      medical students, who experienced both tutored and tutorless groups alternately
      in the two sessions of a year. To examine the effectiveness of tutored and
      tutorless PBL, written examination scores (WES) and self-contentment scores (SCS)
      were statistically analysed. RESULTS: WES averages did not significantly differ
      between the tutored and tutorless groups; however, a significantly greater
      variation was observed in WES in the tutorless group. SCS averages tended to be
      higher in the tutored PBL than in tutorless PBL groups. CONCLUSIONS: Students in
      these tutorless PBL groups performed well in their written examinations, whereas
      those in the tutored PBL groups, achieved this and reported better self
      contentment with their learning experience. Tutorless PBL sessions were
      considered to be comparable to tutored PBL sessions at least in the early stages.

PMID- 24289491
TI  - MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.
AB  - Expression profiling of microRNAs in melanoma lesional skin biopsies compared
      with normal donor skin biopsies, as well as melanoma cell lines compared with
      normal melanocytes, revealed that hsa-miR-206 was down-regulated in melanoma (
      75.4-fold, P = 1.7 * 10(-4)). MiR-206 has been implicated in a large number of
      cancers, including breast, lung, colorectal, ovarian, and prostate cancers;
      however, its role in tumor development remains largely unknown, its biologic
      function is poorly characterized, and its targets affecting cancer cells are
      largely unknown. MiR-206 reduced growth and migration/invasion of multiple
      melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4,
      Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3'UTR
      reporter gene assays revealed that miR-206 inhibited translation of CDK4, Cyclin
      D1, and Cyclin C. Additionally, hsa-miR-206 transfection induced G1 arrest in
      multiple melanoma cell lines. These observations support hsa-miR-206 as a tumor
      suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR-206
      targets.

PMID- 24289492
TI  - Secondary prevention of osteoporosis in non-neck of femur fragility fractures: is
      it value for money? A retrospective, prospective and cross-sectional cohort
      study.
AB  - BACKGROUND: Osteoporosis is one of the commonest bone diseases in which bone
      fragility is increased. Over 300,000 patients present to hospitals in the UK with
      fragility fractures each year, with medical and social care costs - most of which
      relate to hip fracture care - at around L2 billion. The number of these fractures
      rises by 2% a year. The 30 days mortality is 10% and 30% at 1 year. The purpose
      of this study is to review the current practice according to NICE and BOA
      guidelines of secondary prevention of osteoporosis and to suggest changes to
      these guidelines. METHODS: Patients over 50 years old admitted as inpatients to
      our facility with non-neck-of-femur (NOF) fragility fractures in March and
      September 2008 were studied. Retrospectively (March), looking for risk factors
      and if treated or not, then prospectively (September), after introducing the new
      trauma admission sheet. Also cross-sectional study was performed by comparing the
      services provided for NOF and non-NOF fragility fractures in September. Two
      sample t test is used to compare between percentages. RESULTS: Twenty-nine
      percent of fragility fractures are non-NOF fractures with a mean age of 70 years,
      while the remaining 71% are NOF fractures with a mean age of 80 years. There is a
      great difference in the care provided to these patients: non-NOF fragility
      fractures got less attention for assessment of osteoporosis (25%) and obtained
      less interest in investigations by medical staff (11%) and, finally, less
      intentions to treat osteoporosis (35%), compared to NOF fractures in which 35% of
      cases were assessed, 47% were investigated and 71% were treated for osteoporosis.
      Twenty-five percent of NOF fracture patients were found to have previous
      fragility fractures in the preceding years, while only 6% were on osteoporosis
      treatment before the fracture. CONCLUSION: Osteoporosis (a new epidemic) is the
      most common disease of the bone and its incidence is rising rapidly as the
      population ages. Though treatable, it is often left untreated. We believe that
      treating patients with non-NOF fragility fractures from osteoporosis before
      proceeding to NOF fractures would improve their quality of life and reduce the
      burden on hospital services and funding.

PMID- 24289493
TI  - How diverse are diversity assessment methods? A comparative analysis and
      benchmarking of molecular descriptor space.
AB  - Chemical diversity is a widely applied approach to select structurally diverse
      subsets of molecules, often with the objective of maximizing the number of hits
      in biological screening. While many methods exist in the area, few systematic
      comparisons using current descriptors in particular with the objective of
      assessing diversity in bioactivity space have been published, and this shortage
      is what the current study is aiming to address. In this work, 13 widely used
      molecular descriptors were compared, including fingerprint-based descriptors
      (ECFP4, FCFP4, MACCS keys), pharmacophore-based descriptors (TAT, TAD, TGT, TGD,
      GpiDAPH3), shape-based descriptors (rapid overlay of chemical structures (ROCS)
      and principal moments of inertia (PMI)), a connectivity-matrix-based descriptor
      (BCUT), physicochemical-property-based descriptors (prop2D), and a more recently
      introduced molecular descriptor type (namely, "Bayes Affinity Fingerprints"). We
      assessed both the similar behavior of the descriptors in assessing the diversity
      of chemical libraries, and their ability to select compounds from libraries that
      are diverse in bioactivity space, which is a property of much practical relevance
      in screening library design. This is particularly evident, given that many future
      targets to be screened are not known in advance, but that the library should
      still maximize the likelihood of containing bioactive matter also for future
      screening campaigns. Overall, our results showed that descriptors based on atom
      topology (i.e., fingerprint-based descriptors and pharmacophore-based
      descriptors) correlate well in rank-ordering compounds, both within and between
      descriptor types. On the other hand, shape-based descriptors such as ROCS and PMI
      showed weak correlation with the other descriptors utilized in this study,
      demonstrating significantly different behavior. We then applied eight of the
      molecular descriptors compared in this study to sample a diverse subset of sample
      compounds (4%) from an initial population of 2587 compounds, covering the 25
      largest human activity classes from ChEMBL and measured the coverage of activity
      classes by the subsets. Here, it was found that "Bayes Affinity Fingerprints"
      achieved an average coverage of 92% of activity classes. Using the descriptors
      ECFP4, GpiDAPH3, TGT, and random sampling, 91%, 84%, 84%, and 84% of the activity
      classes were represented in the selected compounds respectively, followed by
      BCUT, prop2D, MACCS, and PMI (in order of decreasing performance). In addition,
      we were able to show that there is no visible correlation between compound
      diversity in PMI space and in bioactivity space, despite frequent utilization of
      PMI plots to this end. To summarize, in this work, we assessed which descriptors
      select compounds with high coverage of bioactivity space, and can hence be used
      for diverse compound selection for biological screening. In cases where multiple
      descriptors are to be used for diversity selection, this work describes which
      descriptors behave complementarily, and can hence be used jointly to focus on
      different aspects of diversity in chemical space. 

PMID- 24289494
TI  - Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine
      attacks. A review of new drugs and new administration forms of established drugs.
AB  - INTRODUCTION: The development of sumatriptan, more than 20 years ago, added
      substantially to the characterization of 5-hydroxytryptamine (5-HT) receptors and
      their relevance to acute migraine therapy. Recently, 5-HT1F receptor agonists,
      with no vascular effects, have shown efficacy in the treatment of migraines.
      AREAS COVERED: This evaluation reviews the recent advances in acute migraine
      therapy targeting the 5-HT receptor. Specifically, the authors review the
      pharmacokinetics, pharmacodynamics, clinical efficacy and safety of 5-HT1F
      receptor agonists and new formulations of sumatriptan and dihydroergotamine
      (DHE). EXPERT OPINION: Lasmiditan, a non-vascular acting 5-HT1F receptor agonist,
      is effective in migraine but causes central nervous system-related adverse
      events, which may considerably limit its clinical use. The efficacy of
      transdermal sumatriptan is too low for general use in migraine. Intranasal
      sumatriptan powder could be a step forward compared with oral sumatriptan, but
      comparative trials are needed. Orally inhaled DHE has a very quick systemic
      absorption but the onset of effect in migraine is relatively slow with a maximum
      effect after 2 h. In contrast, orally inhaled DHE results in a low incidence of
      recurrence. None of these reviewed treatments are likely to fulfill patients'
      expectations, and the advancement of acute migraine drugs should likely depend on
      different mechanisms from current 5-HT-related drugs.

PMID- 24289495
TI  - Empowerment, partner's behaviours and intimate partner physical violence among
      married women in Uganda.
AB  - BACKGROUND: There is dearth of knowledge and research about the role of
      empowerment, partners' behaviours and intimate partner physical violence (IPPV)
      among married women in Uganda. This paper examined the influence of women's
      empowerment and partners' behaviours on IPPV among married women in Uganda.
      METHODS: The 2011 Uganda Demographic and Health Survey data were used, selecting
      a weighted sample of 1,307 women in union considered for the domestic violence
      module. Cross tabulations (chi-square tests) and multivariate logistic
      regressions were used to identify factors associated with IPPV. RESULTS: The
      prevalence of IPPV among women in union in Uganda is still high (41%). Women's
      occupation was the only measure of empowerment that was significantly associated
      with IPPV, where women in professional employment were less likely to experience
      IPPV. Women from wealthy households were less likely to experience IPPV. IPPV was
      more likely to be reported by women who had ever had children and witnessed
      parental IPPV. IPPV was also more likely to be reported by women whose husbands
      or partners: accused them of unfaithfulness, did not permit them to meet female
      friends, insisted on knowing their whereabouts and sometimes or often got drunk.
      Women who were afraid their partners were also more likely to report IPPV.
      CONCLUSION: In the Ugandan context, women's empowerment as assessed by the UDHS
      has limited mitigating effect on IPPV in the face of partners' negative
      behaviours and history of witnessing parental violence.

PMID- 24289499
TI  - CaCO3 precipitation, transport and sensing in porous media with in situ
      generation of reactants.
AB  - Ureolytically driven calcite precipitation is a promising approach for inducing
      subsurface mineral precipitation, but engineered application requires the ability
      to control and predict precipitate distribution. To study the coupling between
      reactant transport and precipitate distribution, columns with defined zones of
      immobilized urease were used to examine the distribution of calcium carbonate
      precipitation along the flow path, at two different initial flow rates. As
      expected, with slower flow precipitate was concentrated toward the upstream end
      of the enzyme zone and with higher flow the solid was more uniformly distributed
      over the enzyme zone. Under constant hydraulic head conditions the flow rate
      decreased as precipitates decreased porosity and permeability. The
      hydrolysis/precipitation zone was expected to become compressed in the upstream
      direction. However, apparent reductions in the urea hydrolysis rate and changes
      in the distribution of enzyme activity, possibly due to CaCO3 precipitate
      hindering urea transport to the enzyme, or enzyme mobilization, mitigated
      reaction zone compression. Co-injected strontium was expected to be sequestered
      by coprecipitation with CaCO3, but the results suggested that coprecipitation was
      not an effective sequestration mechanism in this system. In addition, spectral
      induced polarization (SIP) was used to monitor the spatial and temporal evolution
      of the reaction zone. 

PMID- 24289496
TI  - Epidemiology of bloodstream infections in patients with acute myeloid leukemia
      undergoing levofloxacin prophylaxis.
AB  - BACKGROUND: Infections are a common cause of morbidity and mortality in patients
      with acute myeloid leukemia (AML). The evidence for efficacy of antibiotic
      prophylaxis in reducing the mortality rates and the incidence of bacterial
      infections was also reported by a systematic review published by Cochrane in
      2012. The objective of our study was to report the incidence and the etiology of
      bloodstream infections in patients with AML undergoing levofloxacin prophylaxis
      during neutropenic episodes. METHODS: This was a retrospective study of patients
      with diagnosis of AML during 2001-2007. RESULTS: A total of 81 patients were
      included in the study. Two hundred and ninetyone neutropenic episodes were
      studied, of which 181 were febrile. Bacteria isolated from blood cultures were
      mostly Gram-positives during the induction (80%) and Gram-negatives during the
      consolidation (72.4%) phases of chemotherapy. Resistance to ciprofloxacin was
      found in 78.9% of isolated E. coli and it was higher during consolidation and
      higher than the hospital rate. The production of extended spectrum betalactamases
      (ESBL) in E. coli strains was reported in 12.1%, below the reported hospital rate
      during the study period. CONCLUSIONS: Regular microbiology surveillance is needed
      to better understand the impact of levofloxacin prophylaxis in neutropenic
      patients. Our study shows that Gram-positive bacteria are predominant during the
      induction phase of chemotherapy and Gram-negatives during the consolidation. The
      rate of fluoroquinolone resistance in the latter setting, even higher than the
      hospital rate, may suggest to reconsider levofloxacin prophylaxis.

PMID- 24289500
TI  - Treatment of neuropathic pain with the capsaicin 8% patch: is pretreatment with
      lidocaine necessary?
AB  - The capsaicin 8% patch can effectively treat neuropathic pain, but application
      can cause discomfort or a burning sensation. Until March 2013, it was recommended
      that patients be pretreated with a topical anesthetic, for example lidocaine,
      before capsaicin patch application. However, speculation existed over the need
      for pretreatment and its effectiveness in alleviating treatment-associated
      discomfort. This article compares tolerability to and efficacy of the capsaicin
      patch in pretreated and non-pretreated patients. All patients received a single
      capsaicin patch application. Pretreated patients received a lidocaine plaster
      before and intravenous lidocaine and metamizole infusions during capsaicin patch
      application. Pain levels, assessed using a Numeric Rating Scale (NRS), were used
      to determine tolerability and efficacy. All patients (pretreated n = 32; non
      pretreated n = 26) completed 100% of the intended capsaicin patch application
      duration. At the time of capsaicin patch removal, 69% of pretreated and 88% of
      non-pretreated patients reported an NRS score increase, which returned to
      baseline by 6 hours post-treatment. There was no significant difference in mean
      NRS score between patient groups at any time during or after capsaicin patch
      treatment. Response was similar between patient groups; capsaicin patch treatment
      provided rapid and significant pain reductions that were sustained over 12 weeks.
      The same proportion of pretreated and non-pretreated patients reported
      willingness to receive retreatment with the capsaicin patch. This analysis shows
      that the capsaicin 8% patch is generally tolerable, and the small discomfort
      associated with patch application is short-lived. Lidocaine pretreatment does not
      have a significant effect on tolerability, efficacy, or patient willingness to
      receive retreatment.

PMID- 24289501
TI  - Newborn care practices at home and in health facilities in 4 regions of Ethiopia.
AB  - BACKGROUND: Ethiopia is one of the ten countries with the highest number of
      neonatal deaths globally, and only 1 in 10 women deliver with a skilled
      attendant. Promotion of essential newborn care practices is one strategy for
      improving newborn health outcomes that can be delivered in communities as well as
      facilities. This article describes newborn care practices reported by recently
      delivered women (RDWs) in four regions of Ethiopia. METHODS: We conducted a
      household survey with two-stage cluster sampling to assess newborn care practices
      among women who delivered a live baby in the period 1 to 7 months prior to data
      collection. RESULTS: The majority of women made one antenatal care (ANC) visit to
      a health facility, although less than half made four or more visits and women
      were most likely to deliver their babies at home. About one-fifth of RDWs in this
      survey had contact with Health Extension Workers (HEWS) during ANC, but
      nurse/midwives were the most common providers, and few women had postnatal
      contact with any health provider. Common beneficial newborn care practices
      included exclusive breastfeeding (87.6%), wrapping the baby before delivery of
      the placenta (82.3%), and dry cord care (65.2%). Practices contrary to WHO
      recommendations that were reported in this population of recent mothers include
      bathing during the first 24 hours of life (74.7%), application of butter and
      other substances to the cord (19.9%), and discarding of colostrum milk (44.5%).
      The results suggest that there are not large differences for most essential
      newborn care indicators between facility and home deliveries, with the exception
      of delayed bathing and skin-to-skin care. CONCLUSIONS: Improving newborn care and
      newborn health outcomes in Ethiopia will likely require a multifaceted approach.
      Given low facility delivery rates, community-based promotion of preventive
      newborn care practices, which has been effective in other settings, is an
      important strategy. For this strategy to be successful, the coverage of
      counseling delivered by HEWs and other community volunteers should be increased.

PMID- 24289503
TI  - Starch solutions in Australia: the empire strikes back.

PMID- 24289504
TI  - Is maintenance fluid therapy in need of maintenance?

PMID- 24289505
TI  - Can social media bridge the gap between research and practice?

PMID- 24289506
TI  - Intensive care unit mobility practices in Australia and New Zealand: a point
      prevalence study.
AB  - OBJECTIVES: To develop a comprehensive set of items describing physiotherapy
      mobilisation practices for critically ill patients, and to document current
      practices in intensive care units in Australia and New Zealand, focusing on
      patients having > 48 hours of mechanical ventilation. DESIGN: Prospective,
      observational, multicentre, single-day, point prevalence study. PARTICIPANTS AND
      SETTING: All patients in 38 Australian and New Zealand ICUs at 10 am on one of
      three designated days in 2009 and 2010. MAIN OUTCOME MEASURES: Demographic data,
      admission diagnosis and mobilisation practices that had occurred in the previous
      24 hours. RESULTS: 514 patients were enrolled, with 498 complete datasets. Mean
      age was 59.2 years (SD, 16.7 years) and 45% were mechanically ventilated.
      Mobilisation activities were classified into five categories that were not
      mutually exclusive: 140 patients (28%) completed an in-bed exercise regimen, 93
      (19%) sat over the side of the bed, 182 (37%) sat out of bed, 124 (25%) stood and
      89 (18%) walked. Predefined adverse events occurred on 24 occasions (5%). No
      patient requiring mechanical ventilation sat out of bed or walked. On the study
      day, 391 patients had been in ICU for > 48 hours. There were 384 complete
      datasets available for analysis and, of these, 332 patients (86%) were not
      walked. Of those not walked, 76 (23%) were in the ICU for >= 7 days. CONCLUSION:
      Patient mobilisation was shown to be low in a single-day point prevalence study.
      Future observational studies are required to confirm the results.

PMID- 24289507
TI  - Missed medical emergency team activations: tracking decisions and outcomes in
      practice.
AB  - BACKGROUND: Despite extensive work to improve early recognition of and response
      to abnormal vital signs, a failure or delay in response to clinical deterioration
      by activating a medical emergency team (MET) can affect patient safety.
      OBJECTIVES: To determine incidence, management and outcomes of patients having
      vital signs fulfilling MET call criteria during their entire admission, and to
      compare baseline characteristics and outcomes of patients who fulfilled MET call
      criteria with patients who did not. DESIGN: A retrospective chart audit was
      conducted in a private Melbourne hospital. All patients hospitalised for >= 24
      hours in general wards and discharged in the 7-day study period were included.
      Medical records were reviewed for all patients who fulfilled MET criteria to
      assess escalation of care. RESULTS: Of the sample (N = 568), 82 patients (14%)
      had one or more documented vital signs fulfilling MET criteria. Hospital length
      of stay (LOS) for these patients was twice that of those who did not (8.6 days
      versus 4.3 days; P < 0.001). Medical patients were more likely to meet MET
      criteria than surgical patients (P = 0.03), and there were no significant
      differences for sex or between elective and emergency admissions. In the 79
      patients not reviewed by the MET, the primary nurse escalated care for 36
      patients (46%). Nurses independently initiated treatment for 23 of these patients
      (64%) and when unable to, they referred the patient for medical review (36%).
      Presence of MET criteria had resolved within 1 hour for 37 patients (45%) who
      fulfilled criteria. CONCLUSIONS: Despite one in seven patients fulfilling MET
      criteria, MET activation occurred infrequently. The presence of MET criteria was
      associated with a doubling of the hospital LOS. Escalation of care in response to
      detection of MET criteria fulfillment was variable. Further research tracking
      patient management is needed to understand the decision-making process that
      occurs in the presence of clinical deterioration.

PMID- 24289502
TI  - Neurovascular unit dysfunction with blood-brain barrier hyperpermeability
      contributes to major depressive disorder: a review of clinical and experimental
      evidence.
AB  - About one-third of people with major depressive disorder (MDD) fail at least two
      antidepressant drug trials at 1 year. Together with clinical and experimental
      evidence indicating that the pathophysiology of MDD is multifactorial, this
      observation underscores the importance of elucidating mechanisms beyond
      monoaminergic dysregulation that can contribute to the genesis and persistence of
      MDD. Oxidative stress and neuroinflammation are mechanistically linked to the
      presence of neurovascular dysfunction with blood-brain barrier (BBB)
      hyperpermeability in selected neurological disorders, such as stroke, epilepsy,
      multiple sclerosis, traumatic brain injury, and Alzheimer's disease. In contrast
      to other major psychiatric disorders, MDD is frequently comorbid with such
      neurological disorders and constitutes an independent risk factor for morbidity
      and mortality in disorders characterized by vascular endothelial dysfunction
      (cardiovascular disease and diabetes mellitus). Oxidative stress and
      neuroinflammation are implicated in the neurobiology of MDD. More recent evidence
      links neurovascular dysfunction with BBB hyperpermeability to MDD without
      neurological comorbidity. We review this emerging literature and present a
      theoretical integration between these abnormalities to those involving oxidative
      stress and neuroinflammation in MDD. We discuss our hypothesis that alterations
      in endothelial nitric oxide levels and endothelial nitric oxide synthase
      uncoupling are central mechanistic links in this regard. Understanding the
      contribution of neurovascular dysfunction with BBB hyperpermeability to the
      pathophysiology of MDD may help to identify novel therapeutic and preventative
      approaches.

PMID- 24289509
TI  - Statistical analysis plan for the HEAT trial: a multicentre randomised placebo
      controlled trial of intravenous paracetamol in intensive care unit patients with
      fever and infection.
AB  - BACKGROUND AND OBJECTIVE: We describe the statistical analysis plan (SAP) for the
      Permissive Hyperthermia through Avoidance of Paracetamol in Known or Suspected
      Infection in the Intensive Care Unit (HEAT) trial, a 700-patient, prospective,
      randomised, Phase 2b, multicentre, double-blind, parallel-groups, placebo
      controlled trial of paracetamol administration for the treatment of fever in
      critically ill patients with known or suspected infection. METHODS: The data
      fields described are those outlined in the study protocol published previously.
      We describe the plan for the presentation and comparison of baseline
      characteristics, process measures and outcomes. We describe baseline
      characteristics, and define and categorise trial outcomes according to their
      assigned importance. RESULTS AND CONCLUSIONS: We developed an SAP for the HEAT
      trial, and produced a mock Consolidated Standards of Reporting Trials diagram and
      tables. Our prespecified SAP accords with high-quality standards of internal
      validity and should minimise future analysis bias.

PMID- 24289508
TI  - Mortality of rapid response team patients in Australia: a multicentre study.
AB  - BACKGROUND: Most studies of the rapid response team (RRT) investigate the effect
      of introducing an RRT on outcomes of all hospitalised patients. Less information
      exists on RRT patient epidemiology, or changes in RRT call numbers with time.
      OBJECTIVES: To estimate the inhospital mortality of patients subject to RRT
      review, the proportion of inhospital deaths reviewed by the RRT, and changes in
      annual RRT call numbers with time. METHOD: Retrospective observational study in
      adult RRT equipped Australian hospitals for up to 10 years (2000-2009).
      PARTICIPANTS AND OUTCOME MEASURES: Thirty-four per cent (35/102) of the
      Australian adult RRT-equipped hospitals provided annual hospital admissions and
      deaths, intensive care unit admissions and RRT calls. They also provided the
      number of patients reviewed by the RRT and the number of inhospital deaths in
      such patients. RESULTS: Over the study period, there were 4.91 million hospital
      admissions, 196 488 ICU admissions and 99 377 RRT calls. Most data arose from
      Victoria, New South Wales and Western Australia, and from public tertiary
      hospitals. Among the 27 hospitals contributing at least 4 years of data, annual
      RRT calls per 1000 admissions was higher in the last year compared with the first
      year of data submission in 23 hospitals (range of increase, 11.9%- 777.4%;
      median, 90%; interquartile range, 40%-180%). In the remaining four hospitals,
      annual RRT calls per 1000 admissions were lower in the last year compared with
      the first year (range of decrease, - 5.5% to - 29.8%). Among the 70 924 RRT
      patients for whom the outcome was known, there were 17 260 deaths (24.3%). We
      calculate that the RRT reviewed 17 260 of 79 476 patients (21.7%) who died in
      hospital over the study period. In the 2008-09 financial year, there were 18 800
      RRT calls for at least 14 743 patients. CONCLUSIONS: Annual RRT calls are
      increasing in many Australian hospitals, and now affect more than 14 700 patients
      annually. Inhospital mortality of RRT patients is about 25%, and about 20% of
      patients who die in hospital are reviewed by the RRT. Further research is needed
      to understand the reason for the high inhospital mortality of RRT patients.

PMID- 24289511
TI  - Sodium administration in critically ill patients in Australia and New Zealand: a
      multicentre point prevalence study.
AB  - BACKGROUND: Inadvertent sodium administration in excess of recommended daily
      requirements has been reported during routine care of critically ill patients.
      AIM: To determine the amount and sources of sodium administered in Australian and
      New Zealand intensive care units. DESIGN, SETTING AND PARTICIPANTS: Prospective,
      observational, single-day, point prevalence survey conducted in 46 Australian and
      New Zealand ICUs on 21 September 2011. All patients present in ICU at 10 am and
      not receiving an oral diet on the study day were evaluated. Demographic data, ICU
      admission diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II
      score and sources of sodium administration over the study day were recorded.
      RESULTS: 356 patients (64% male) were enrolled. Mean (SD) age and weight were
      58.5 years (18.0 years) and 81.6 kg (24.0 kg), respectively. Mean ICU admission
      APACHE II score was 20 (SD, 8). Overall median (interquartile range [IQR]) sodium
      administration was 224.5 mmol (IQR, 144.9-367.6 mmol), or 2.8 mmol/kg (IQR, 1.6
      4.7 mmol/kg). Among patients who were on Day 2-10 of their ICU admission on the
      study day, sodium sources and amounts administered were: i) maintenance or
      replacement intravenous (IV) infusions, 69.3mmol; 30.9% of all sodium sources;
      ii) IV fluid boluses, 36.5 mmol; 16.3%; iii) IV drug boluses, 27.6 mmol; 12.3%;
      iv) enteral nutrition, 26.5 mmol; 11.8%; v) IV drug infusions, 19.3 mmol; 8.6%;
      vi) IV flushes, 16.6mmol; 7.4%; vii) blood products, 13.5 mmol; 6%; viii) IV
      antimicrobials, 11.2mmol; 5%; and ix) parenteral nutrition, 4.3 mmol; 1.9%.
      Factors associated with sodium administration were site (P = 0.04), age (P <
      0.001), administered fluid (P = 0.03) and day of ICU stay (P = 0.01) (multiple
      linear regression). CONCLUSION: This point prevalence study suggests that sodium
      administration in excess of recommended daily requirements may be common in
      Australia and New Zealand ICUs. The main sodium source was IV maintenance fluids,
      followed by fluid boluses and drug boluses.

PMID- 24289513
TI  - The Protocolised Management in Sepsis (ProMISe) trial statistical analysis plan.
AB  - BACKGROUND: The Protocolised Management in Sepsis (ProMISe) trial is an open,
      multicentre, randomised controlled trial (RCT) of the clinical effectiveness and
      cost-effectiveness of early, goal directed, protocolised resuscitation compared
      with usual resuscitation for patients presenting to emergency departments (EDs)
      in the United Kingdom with early signs of severe sepsis or septic shock. The
      rationale for the ProMISe trial derives from a single-centre United States RCT
      that reported a reduction in hospital mortality from 46.5% to 30.5%. OBJECTIVE:
      To describe the proposed statistical analyses for the evaluation of clinical
      effectiveness for the ProMISe trial. It is important to complete this plan before
      inspecting the data, and before completion of two related international studies,
      so that post-hoc, data-derived decisions are avoided. METHODS: The primary and
      secondary outcomes were defined precisely, and the approach to safety monitoring
      and data collection summarised, with a description of the planned statistical
      analyses including prespecified subgroup and secondary analyses. RESULTS: The
      primary outcome is all-cause mortality at 90 days. The primary analysis will be
      reported as a relative risk and absolute risk reduction and tested with the
      Fisher exact test. Prespecified subgroup analyses will be based on age, baseline
      Medical Emergency Department Sepsis score, baseline Sequential Organ Failure
      Assessment score, and time from ED presentation to randomisation. Secondary
      analyses include adjustment for baseline covariates, estimation of learning curve
      effects and adjustment for noncompliance. CONCLUSION: In keeping with best
      practice, we have developed a statistical analysis plan for the ProMISe trial and
      place it in the public domain before inspecting data from the trial.

PMID- 24289510
TI  - Oxygen therapy in non-intubated adult intensive care patients: a point prevalence
      study.
AB  - BACKGROUND: Oxygen is commonly administered to intensive care unit patients.
      Although there is knowledge of how oxygen is administered to mechanically
      ventilated patients, there are few data about its use in non-intubated ICU
      patients. OBJECTIVE: To describe how oxygen therapy is prescribed, administered
      and monitored for non-intubated patients in New Zealand and Australian ICUs.
      DESIGN, PARTICIPANTS AND SETTING: Prospective, observational, binational,
      multicentre, 1-day point prevalence study of all adult patients in 40 New Zealand
      and Australian ICUs at 10 am on a study day. MAIN OUTCOME MEASURES: We collected
      patient demographic data, 28-day mortality and details of oxygen therapy (oxygen
      therapy prescription, oxygen delivery device use and oxygen saturation targets).
      RESULTS: We audited 506 patients, of whom 178 (35.2%) were not intubated but
      receiving oxygen therapy; 59.5% were men. Their mean age was 57.3 years (SD, 18.8
      years), mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was
      16.2 (SD, 7.3) and 47.2% were admitted after surgery. Most patients (66%)
      received oxygen via simple nasal cannulae, and patients also received oxygen via
      open face mask, nasal high-flow and noninvasive ventilation. A documented
      prescription for oxygen therapy was in place for 24.4% of patients, and we
      considered 7% to be complete and comprehensive. CONCLUSIONS: Oxygen therapy is
      commonly administered to non-intubated adult patients in New Zealand and
      Australian ICUs. Most patients received oxygen by simple nasal cannulae, and
      oxygen therapy prescriptions were often absent or incomplete. We advise
      continuing education to ensure that oxygen is prescribed, administered and
      documented correctly.

PMID- 24289514
TI  - Intensive care unit occupancy after introduction of the emergency department 4
      hour discharge rule at a tertiary referral hospital in Western Australia.
AB  - BACKGROUND: The 4-hour rule has been introduced in Western Australia, requiring
      that emergency department (ED) patients be admitted to hospital or discharged
      from the ED within 4 hours of presentation. We hypothesised that this rule might
      have been associated with changes in medical emergency team (MET) calls and
      intensive care unit exit bed block. METHODS: Hospital databases were examined to
      determine compliance with the 4-hour rule, the effect on ICU exit bed block, and
      the number of MET calls, in 2008 (before introduction of the 4-hour rule) and
      2011 (after introduction of the 4-hour rule). We also measured background ICU and
      hospital activity in 2008 and 2011. RESULTS: Monthly compliance with the 4-hour
      rule ranged from 35%-46% in 2008 to 64%-75% in 2011 (P < 0.0001). There was a
      marked increase in bed block days for patients in the ICU between 2008 (before
      introduction of the 4-hour rule) and 2011 (after introduction of the 4-hour rule)
      (P = 0.05). The increase in ICU bed block-days could not be explained by a
      difference in ICU occupancy, as there was a reduction in ICU bed-days between
      2008 and 2011 (P = 0.014). There was a reduction in hospital mortality rate
      between 2008 and 2011 (P < 0.001). There was no significant increase in the
      number of MET calls from 2008 to 2011 (P = 0.221). Hospital activity
      (separations) increased from 2008 to 2011 (P < 0.0001). DISCUSSION: The
      introduction of the 4-hour rule was associated with increased exit block from the
      ICU, but not with increased MET calls to attend to unstable or deteriorating ward
      patients. Introduction of the 4-hour rule was associated with a small reduction
      in hospital mortality.

PMID- 24289512
TI  - Protocolized Care for Early Septic Shock (ProCESS) statistical analysis plan.
AB  - BACKGROUND: The Protocolized Care for Early Septic Shock study is a randomised,
      multicentre, prospective, three-arm, parallel-group trial of alternative
      resuscitation strategies for early septic shock. OBJECTIVE: To state our analysis
      plan for trial data. METHODS: Our plan is to guide data collection and analysis
      using pre-existing definitions and testing, with local consensus-based efforts
      where needed. We examine protocolised care (two experimental approaches) and
      compare this to usual "wild type" care. RESULTS: Our plan is to address three
      aims (clinical efficacy, biology of illness and recovery, and costs and cost
      effectiveness) and four hypotheses, and we specify rules for handling data and
      determining outcomes. CONCLUSION: By using measures to maintain study conduct and
      analysis rigour, we hope to improve understanding of early septic shock
      resuscitation and care of patients.

PMID- 24289515
TI  - Near-infrared spectroscopy of the thenar eminence to estimate forearm blood flow.
AB  - BACKGROUND: Near-infrared spectroscopy of the thenar eminence (NIRSth) can be
      used at the bedside to assess tissue oxygenation (StO2), the reperfusion response
      to ischaemia and the tissue haemoglobin index (THI). Its ability to estimate
      forearm blood flow (FBF) has not previously been assessed. OBJECTIVES: We aimed
      to test whether short-lived venous occlusion-induced changes in NIRSth-derived
      THI (DeltaTHI/ minute) correlate with strain gauge plethysmography (SGP)
      measurements. METHODS: We measured FBF in nine volunteers with SGP by venous
      occlusion, while estimating DeltaTHI. Measurements were obtained in two forearm
      positions (elevated and horizontal) at baseline and during induced hyperaemia.
      RESULTS: We performed 246 paired measurements at rest and after occlusion-induced
      hyperaemia. At rest, mean SGP-estimated FBF was 3.5-3.6 mL/dL/minute at baseline,
      compared with 12.9-13.6 mL/dL/minute during hyperaemia. At rest, DeltaTHI was 6.1
      8.2/minute, compared with 29.7-32.5/minute during hyperaemia. DeltaTHI was a
      significant predictor of SGP FBF (P < 0.01), with stronger correlation during
      hyperaemia (P < 0.01). An equation was developed to convert DeltaTHI/minute into
      FBF at mL/dL/minute (FBF = 0.362 DeltaTHI/minute + 0.864). CONCLUSIONS: NIRSth
      can be used to estimate FBF. Given its portability and its ability to also
      measure StO2 and vascular reactivity, NIRSth can assist in providing a
      comprehensive bedside assessment of the forearm circulation in critically ill
      patients.

PMID- 24289516
TI  - Assessment of the distribution and professional roles of the new Fellows of the
      College of Intensive Care Medicine of Australia and New Zealand.

PMID- 24289517
TI  - Patient comfort in the intensive care unit: a multicentre, binational point
      prevalence study of analgesia, sedation and delirium management.

PMID- 24289518
TI  - Valproic acid reduces neuritic plaque formation and improves learning deficits in
      APP(Swe) /PS1(A246E) transgenic mice via preventing the prenatal hypoxia-induced
      down-regulation of neprilysin.
AB  - AIMS: Previously, we have documented that prenatal hypoxia can aggravate the
      cognitive impairment and Alzheimer's disease (AD) neuropathology in APP(Swe)
      /PS1(A246E) (APP/PS1) transgenic mice, and valproic acid (VPA) can prevent
      hypoxia-induced down-regulation of beta-amyloid (Abeta) degradation enzyme
      neprilysin (NEP) in primary neurons. In this study, we have investigated the
      molecular mechanisms of VPA's anti-AD effects and found that VPA can reduce the
      prenatal hypoxia-induced neuritic plaque formation and improve the learning
      deficits in the AD mouse model. METHODS: The pregnant APP/PS1 transgenic mice
      were exposed in a hypobaric chamber. Neuritic plaque staining, Morris water maze,
      and enzyme-linked immunosorbent assay (ELISA) were used to detect the effects of
      VPA on Abeta neuropathology, learning, and memory. Chromatin immunoprecipitation
      (ChIP) assays and real-time PCR (RT-PCR) were used to determine the effect of VPA
      on the histone3 acetylation (H3-Ace). RESULTS: We found that VPA can inhibit
      neuritic plaque formation and improve the learning and memory in the prenatal
      hypoxic APP/PS1 transgenic mice. In addition, VPA treatment can decrease the
      soluble and insoluble Abeta42 levels and increase the NEP expression via up
      regulation of H3-Ace in the APP/PS1 transgenic mice. CONCLUSION: Valproic acid is
      able to attenuate the prenatal hypoxia-induced Abeta neuropathology and learning
      and memory deficits via inhibiting the activation of histone deacetylase 1
      (HDAC1), preventing the decrease in H3-Ace in the NEP promoter regions and
      reducing the down-regulation of NEP.

PMID- 24289519
TI  - Prognostic and predictive value of Phospho-p44/42 and pAKT in HER2-positive
      locally advanced breast cancer patients treated with anthracycline-based
      neoadjuvant chemotherapy.
AB  - BACKGROUND: To evaluate the predictive and prognostic value of various molecular
      factors associated with the Ras/MAPK and PI3K/Akt signaling pathways in HER2
      positive locally advanced breast cancer patients treated with anthracycline-based
      neoadjuvant chemotherapy (NAC). METHODS: A total of 113 patients were recruited
      in this retrospective study. Core needle biopsies and excision samples were
      assessed through immunohistochemistry for various biomarkers, including IGF-1R,
      Phospho-p44/42, Ki67, pAKT, PTEN, p27, and cyclinD1. The changes in these
      biomarkers after NAC and their predictive and prognostic values were
      investigated. RESULTS: Significant decreases in Ki67, Phospho-p44/42, and pAKT
      expression were observed after treatment (30.7% vs. 18.1%, 36.4% vs. 18.9%, and
      35.1% vs. 16.4%, respectively). The decreases in Phospho-p44/42, pAKT, and Ki67
      expression were strongly associated with the response to anthracycline treatment
      (P = 0.027, P = 0.031, and P = 0.008, respectively). In a multivariate survival
      analysis, Phospho-p44/42 expression after neoadjuvant chemotherapy and lymph node
      status were significant independent prognostic factors of both relapse-free
      survival and overall survival. CONCLUSIONS: Reductions in Ki-67, Phospho-p44/42,
      and pAKT expression are related to the clinical response to anthracycline-based
      NAC in HER2-positive breast cancer patients. High pAKT expression prior to NAC
      had a better clinical response. Phospho-p44/42 expression and lymph node status
      after NAC could be useful for determining relapse-free survival and overall
      survival.

PMID- 24289520
TI  - Impact of repeated ivermectin treatments against onchocerciasis on the
      transmission of loiasis: an entomologic evaluation in central Cameroon.
AB  - BACKGROUND: Annual community-directed treatment with ivermectin (CDTI) have been
      carried out since 1999 in the Lekie division (central region of Cameroon where
      most cases of Loa-related post ivermectin severe adverse events were reported) as
      part of the joined activities of the African Programme for Onchocerciasis Control
      (APOC) and Mectizan(r) Donation Program (MDP). As large-scale administration of
      ivermetine was demonstrated to be an efficient means to control loiasis
      transmission, it was hypothesized that CDTI would have lowered or halted the
      transmission of Loa loa in the Lekie division after 13 years of annual drug
      administration, indicating a possible reduction in the occurrence of Loa-related
      post-ivermectin severe adverse events. METHODS: A 4-month entomologic study was
      carried out from March to June 2012 in the Lekie division to evaluate the impact
      of 13 years of CDTI on the transmission of L. loa whose baseline data were
      recorded in 1999-2000. RESULTS: There was a significant reduction in the
      infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000
      to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR)
      (percentage of flies harboring head L3 larvae), potential infective rate (PIR)
      (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average
      L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per
      potentially infective fly) for both C. silacea and C. dimidiata were not
      significantly different between the two investigation periods. The biting density
      (BD) was almost three-fold higher in 2012 for C. silacea but not for C.
      dimidiata. The transmission potential (TP) which is a function of the BD, was
      higher in the present study than in the baseline investigation for each species.
      CONCLUSION: The infection rate remaining high, the high TP and the stability
      observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that
      transmission of L. loa is still active. This is an indication that the risk of
      occurrence of severe adverse events such as fatal encephalopathies is still
      present, especially for heavily microfilaria-loaded people taken ivermectin for
      the first time.

PMID- 24289521
TI  - The impact of preparatory activities on medical school selection outcomes: a
      cross-sectional survey of applicants to the University of Adelaide Medical School
      in 2007.
AB  - BACKGROUND: Selection into medical school is highly competitive with more
      applicants than places. Little is known about the preparation that applicants
      undertake for this high stakes process. The study aims to determine what
      preparatory activities applicants undertake and what difficulties they encounter
      for each stage of the application process to medical school and in particular
      what impact these have on the outcome. METHODS: A cross-sectional survey of 1097
      applicants who applied for a place in the University of Adelaide Medical School
      in 2007 and participated in the UMAT (Undergraduate Medicine and Health Sciences
      Admission Test) and oral assessment components of the selection process. The main
      outcome measures were an offer of an interview and offer of a place in the
      medical school and were analysed using logistic regression. RESULTS: The odds of
      a successful outcome increased with each additional preparatory activity
      undertaken for the UMAT (odds ratio 1.22, 95% confidence interval 1.11 to 1.33; P
      < 0.001) and the oral assessment (1.36, 1.19 to 1.55; P < 0.001) stage of
      selection. The UMAT preparatory activities associated with the offer of an
      interview were attendance of a training course by a private organisation (1.75,
      1.35 to 2.27: P < 0.001), use of online services of a private organisation (1.58,
      1.23 to 2.04; P < 0.001), and familiarising oneself with the process (1.52, 1.15
      to 2.00; p = 0.021). The oral assessment activities associated with an offer of a
      place included refining and learning a personal resume (9.73, 2.97 to 31.88; P <
      0.001) and learning about the course structure (2.05, 1.29 to 3.26; P =
      0.022).For the UMAT, applicants who found difficulties with learning for this
      type of test (0.47, 0.35 to 0.63: P < 0.001), with the timing of UMAT in terms of
      school exams (0.48, 0.5 to 0.66; P < 0.001) and with the inability to convey
      personal skills with the UMAT (0.67, 0.52 to 0.86; P = 0.026) were significantly
      less likely to be offered an interview. CONCLUSIONS: Medical schools make an
      enormous effort to undertake a selection process that is fair and equitable and
      which selects students most appropriate for medical school and the course they
      provide. Our results indicate that performance in the selection processes can be
      improved by training. However, if these preparatory activities may be limited to
      those who can access them, the playing field is not even and increasing equity of
      access to medical schools will not be achieved.

PMID- 24289522
TI  - [Gunshot wounds caused by non-lethal ammunition on the porcine model post
      mortem].
AB  - In this article we focus on the effects of so called non-lethal ammunition. We
      studied possible mechanism of firearm injury formation as a consequence of using
      firearm on the body, to present a more comprehensive material in wound
      ballistics. We pointed out possible actions of a projectile causes on human,
      respectively other animal organisms, as well as to a manner in which an injury is
      caused by rifles or shotguns using non-lethal ammunition with rubber projectiles.
      In the experiment, we have focused on macroscopic analysis of the tissue
      penetrated by a rubber projectile fired from a long firearm and pump-action
      shotgun while focusing on the anatomical-morphological analysis of entry wounds
      to determine the effectiveness respectively, the wounding potential of the
      projectile. The results of the experiment based on the macroscopic analysis of
      entry wounds, cavities and exit wounds, show that when a rubber projectile
      penetrates the body it causes loss of the tissue (i.e. the minus effect) and
      mechanical disruption of the tissue similar to lethal projectile. Based on the
      measures and ballistic computations we concluded that in specific cases, like for
      example in a close range hit, a penetration of vital organs can cause serious or
      even lethal injuries.

PMID- 24289523
TI  - Vertebral artery aneurysm rupture: an autopsy case.
AB  - Vertebral artery aneurysm rupture is a rare cause of sudden death. The presented
      case was 31-year-old woman who was found dead in her bedroom. Family members
      stated that she had history of one year duration childhood epilepsy treatment.
      Autopsy investigation revealed 5 mm in diameter aneurysm, ruptured in 1 mm area,
      localized on the trunk of the right vertebral artery. We described an autopsy
      case of sudden unexpected death due to ruptured vertebral artery aneurysm.

PMID- 24289524
TI  - Death due to traumatic tracheo-brachiocephalic artery fistula: an autopsy case.
AB  - Tracheo-brachiocephalic artery fistulas were rarely reported lesions often
      described in cases with tracheostomy procedures. Reported case was 26 year-old
      male drainage worker, trapped under the stony soil while excavating drainage
      canal. Rescue operation was performed, but he was reached dead. Provincial
      prosecutor mandated autopsy after crime scene investigation. Autopsy examination
      revealed traumatically formed tracheo-brachiocephalic fistula. We aimed to report
      an intersting case of traumatic tracheo-brachiocephalic artery fistula identified
      in forensic autopsy.

PMID- 24289525
TI  - Xylene; a useful marker for agricultural products ingestion.
AB  - Here we report about a case of malathion (an organophosphate insecticide)
      ingestion. Headspace analysis of stomach content provided useful information for
      screening of toxic chemicals. We should pay attention to solvents used in
      commercial industrial products.

PMID- 24289526
TI  - Aortic arch blunt injury in front-seat passenger.
AB  - Aortic arch blunt injury has highly lethal nature. Because the physical
      examination findings are subtle, immediate medical evaluation is very important.
      The case was a 72-year-old woman. Massive haemorrhage in the left haemotorax,
      contusion area in the left lung and a traumatic transection of the distal aortic
      arch was observed during autopsy. We described intersting autopsy case of aortic
      arch blunt injury.

PMID- 24289527
TI  - A report on the Global Open Water Swimming (GOWS) Conference, Cork, Ireland, 12th
      October 2013.
AB  - The third Global Open Water Swimming Conference was for the first time held in
      Europe. Researchers, swim pioneers and leading marathon swimmers came together to
      present research related to the water environment, pioneer swims, young and old
      marathon swimmers and human physiology. 

PMID- 24289528
TI  - Acceptability of long-acting, progestin-only contraception in Europe: a two-year
      prospective, non-interventional study.
AB  - OBJECTIVES To compare two-year continuation rates and user satisfaction with the
      levonorgestrel releasing-intrauterine system (LNG-IUS) and the etonogestrel
      releasing-subdermal implant (ENG implant) in women in Europe. METHODS This
      prospective, non-interventional study was undertaken at 72 sites in France (n =
      61), Great Britain (n = 2), Ireland (n = 3) and Slovakia (n = 6). Women opting to
      switch their method of contraception to the LNG-IUS or the ENG implant were
      followed-up over 24 months to document continuation and satisfaction with their
      chosen contraceptive method. Reasons for discontinuation were documented. RESULTS
      The data analysed were based on 363 women (LNG-IUS [n = 247] and ENG implant [n =
      116]), aged 20 to 45 years, with at least one follow-up visit after contraceptive
      placement. The documented cumulative continuation rate was 82% in the LNG-IUS
      group and 67% in the ENG implant group at 24 months. The documented
      discontinuation rates were 13% and 17%, respectively. Bleeding problems were
      cited as reason for discontinuation in 4% and 11% of women in the LNG-IUS and ENG
      implant groups, respectively. CONCLUSIONS The LNG-IUS is associated with higher
      continuation rates and user satisfaction than the ENG implant in this study of
      women in Europe, though the groups were not similar in all respects. Bleeding
      problems with the ENG implant account for most of the reasons for discontinuing
      its use.

PMID- 24289529
TI  - Translational profiling in childhood acute lymphoblastic leukemia: no evidence
      for glucocorticoid regulation of mRNA translation.
AB  - BACKGROUND: Glucocorticoids (GCs) are natural stress induced steroid hormones
      causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are
      the central component in the treatment of lymphoid malignancies, in particular
      childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating
      gene transcription, which has been intensively studied by us and others. GC
      control of mRNA translation has also been reported but has never been assessed
      systematically. In this study we investigate the effect of GCs on mRNA
      translation on a genome-wide scale. RESULTS: Childhood T- (CCRF-CEM) and
      precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational
      profiling", a technique combining sucrose-gradient fractionation followed by
      Affymetrix Exon microarray analysis of mRNA from different fractions, to assess
      the translational efficiency of the expressed genes. Analysis of GC regulation in
      ribosome-bound fractions versus transcriptional regulation revealed no
      significant differences, i.e., GC did not entail a significant shift between
      ribosomal bound and unbound mRNAs. CONCLUSIONS: In the present study we analyzed
      for the first time possible effects of GC on the translational efficiency of
      expressed genes in two chALL model systems employing whole genome polysome
      profiling. Our results did not reveal significant differences in translational
      efficiency of expressed genes thereby arguing against a potential widespread
      regulatory effect of GCs on translation at least in the investigated in vitro
      systems.

PMID- 24289530
TI  - Insights on the facet specific adsorption of amino acids and peptides toward
      platinum.
AB  - Engineering shape-controlled bionanomaterials requires comprehensive
      understanding of interactions between biomolecules and inorganic surfaces. We
      explore the origin of facet-selective binding of peptides adsorbed onto Pt(100)
      and Pt(111) crystallographic planes. Using molecular dynamics simulations, we
      show that upon adsorption the peptides adopt a predictable conformation. We
      compute the binding energies of the amino acids constituting two adhesion
      peptides for Pt, S7, and T7 and demonstrate that peptides' surface recognition
      behavior that makes them unique among populations originates from differential
      adsorption of their building blocks. We find that the degree of peptide binding
      is mainly due to polar amino acids and the molecular architecture of the peptides
      close to the Pt facets. Our analysis is a first step in the prediction of
      enhanced affinity between inorganic materials and a peptides, toward the
      synthesis of novel nanomaterials with programmable shape, structure, and
      properties. 

PMID- 24289531
TI  - A cross-sectional study of low physical fitness, self-rated fitness and
      psychosocial factors in a sample of Finnish 18- to 64-year-old men.
AB  - BACKGROUND: The biological risk factors of inactivity and poor cardiorespiratory
      fitness are well established. However, risk groups are hard to reach and they may
      have misperceptions of their need for change. This study explored self-ratings of
      physical fitness (PF) and the relationship between objectively estimated physical
      fitness (PFI) and psychosocial factors among Finnish men of working-age. METHODS:
      Cross-sectional data on 899 Finnish men (aged 18-64) were collected in 2011.
      Health- related physical fitness was evaluated with a physical fitness index
      calculated from the results of selected fitness tests. The men were subsequently
      classified into three groups: low, moderate and high PFI. Psychosocial factors
      and self-rated fitness were elicited in the questionnaire. The data were analysed
      with crosstabulations, chi square-test and logistic regression analysis. RESULTS:
      One-fifth of the participants had low PFI. Forty-five per cent of the low-fit
      middle-aged (35-49 years) men self-reported poor PF, while 80 per cent of the
      younger (18-34 years) low-fit men self-reported moderate or good PF. The health
      benefits and recommended dose of physical activity were well known in all the PFI
      categories. The low-fit men were health conscious, but lacked adequate exercise
      skills, self-efficacy and social support. However, logistic regressions revealed
      that, in the younger men, likelihood of better knowledge was not related to
      higher PFI. Among the 50-to-64-year-old men, high PFI was not associated with a
      higher social support. CONCLUSIONS: Poor exercise skills, self-efficacy and
      social support were related to low PFI. Physical activity promotion for low-fit
      men should take into account age differences in the relationship between
      psychosocial factors and physical fitness. Thus, new and effective ways to
      establish social support and motivation for physical activity among low-fit men
      in all working-age groups are needed. Further research is also warranted on
      whether estimation of PFI could be used as a practical health counselling tool.

PMID- 24289532
TI  - HPV clearance in postpartum period of HIV-positive and negative women: a
      prospective follow-up study.
AB  - BACKGROUND: HPV persistence is a key determinant of cervical carcinogenesis. The
      influence of postpartum on HPV clearance has been debated. This study aimed to
      assess HPV clearance in later pregnancy and postpartum among HIV-positive and
      negative women. METHODS: We conducted a follow-up study with 151 HPV-positive
      women coinfected with HIV, in 2007-2010. After baseline assessment, all women
      were retested for HPV infection using PCR in later pregnancy and after delivery.
      Multivariable logistic regressions assessed the putative association of
      covariates with HPV status in between each one of the successive visits. RESULTS:
      Seventy-one women (47%) have eliminated HPV between the baseline visit and their
      second or third visits. HIV-positive women took a significantly longer time (7.0
      +/- 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 +/- 3.0
      months). HPV clearance was significantly more likely to take place after delivery
      than during pregnancy (84.5% x 15.5%). CONCLUSIONS: Both HIV-positive and
      negative women presented a significant reduction in HPV infection during the
      postpartum period. HIV-positive status was found to be associated with a longer
      period of time to clear HPV infection in pregnant women.

PMID- 24289534
TI  - Synthesis of coffinite, USiO4, and structural investigations of UxTh(1-x)SiO4
      solid solutions.
AB  - The miscibility behavior of the USiO4-ThSiO4 system was investigated. The end
      members and 10 solid solutions UxTh(1-x)SiO4 with x = 0.12-0.92 were successfully
      synthesized, without formation of other secondary uranium or thorium phases.
      Lattice parameters of the solid solutions evidently follow Vegard's Law.
      Investigation of the local structure with EXAFS reveals small differences between
      the U and Th environment attributed to different atomic radii of the metal atoms
      but no implications for a miscibility gap. The data provided confirm complete
      miscibility for the system USiO4-ThSiO4. The structure of the end members was
      studied in detail with XRD and discussed with special regard to the oxygen
      positions and the often neglected Si-O bond length. USiO4 could be obtained
      without UO2 impurities and the lattice parameters derived from Rietveld
      refinement as c = 6.2606(3) A and a = 6.9841(3) A. The Si-O distance in USiO4
      appears to be 1.64 A, which is more reasonable than earlier reported values. 

PMID- 24289533
TI  - Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody
      enhances the antitumor immunity of interferon-alpha gene therapy for pancreatic
      cancer.
AB  - We have reported that interferon (IFN)-alpha can attack cancer cells by multiple
      antitumor mechanisms including the induction of direct cancer cell death and the
      enhancement of an immune response in several pancreatic cancer models. However,
      an immunotolerant microenvironment in the tumors is often responsible for the
      failure of the cancer immunotherapy. Here we examined whether the suppression of
      regulatory T cells (Tregs) within tumors can enhance an antitumor immunity
      induced by an intratumoral IFN-alpha gene transfer. First we showed that an
      intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF
      receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the
      function of Tregs, significantly inhibited subcutaneous tumor growth in a murine
      pancreatic cancer model. The anti-GITR mAb was then combined with the
      intratumoral injection of the IFN-alpha-adenovirus vector. The treatment with the
      antibody synergistically augmented the antitumor effect of IFN-alpha gene therapy
      not only in the vector-injected tumors but also in the vector-uninjected tumors.
      Immunostaining showed that the anti-GITR mAb decreased Foxp3(+) cells
      infiltrating in the tumors, while the intratumoral IFN-alpha gene transfer
      increased CD4(+) and CD8(+) T cells in the tumors. Therefore, the combination
      therapy strongly inclined the immune balance of the tumor microenvironment in an
      antitumor direction, leading to a marked systemic antitumor effect. The CCR5
      expression on Tregs was downregulated in the antibody-treated mice, which may
      explain the decrease of tumor-infiltrating Tregs. The combination of Treg
      suppression by GITR mAb and the tumor immunity induction by IFN-alpha gene
      therapy could be a promising therapeutic strategy for pancreatic cancer. 

PMID- 24289535
TI  - Active trachoma two years after three rounds of azithromycin mass treatment in
      Cheha District Gurage Zone, Southern Ethiopia.
AB  - BACKGROUND: Azithromycin mass distribution was given to residents of Gurage zone
      Cheha district in 2004, 2005 and 2006 for three consecutive years with more than
      90% coverage. The effect of treatment in the study community was not yet
      determined. The present study was therefore designed to assess the effect of
      azithromycin on the prevalence of active trachoma two years after three rounds of
      mass treatment of the community at Cheha district, Gurage zone. METHODS: A
      multistage stratified cluster random survey was employed to determine the
      prevalence of active trachoma among children aged 1 to 9. Selected children were
      examined for trachoma using the simplified WHO grading system and their
      households were assessed for trachoma risk factors. RESULTS: This survey
      demonstrated that the prevalence of active trachoma in the study community was
      22.8% (95% CI 18.24% - 27.36%) that was lower than that of Southern Nations,
      Nationalities, and People's Regional prevalence (33.2%) in 2006. Only 27.6% (95%
      CI 25.7% - 30.1%) of the study population had a safe and clean water supply,
      whereas 42.7% (95% CI 39.8% - 46.2%) of the visited households had simple pit
      latrines. CONCLUSION: This survey demonstrated that despite repeated mass oral
      azithromycin distributions, the prevalence of active trachoma was still high.
      Therefore, the other components of the SAFE strategy such as fly control program,
      improving the water sources, measures to improve face washing and construction of
      utilizable latrines that are being implemented through the health extension
      package have to be integrated with mass azithromycin treatment to eliminate
      active trachoma in the district.

PMID- 24289536
TI  - Recent breeding history of dog breeds in Sweden: modest rates of inbreeding,
      extensive loss of genetic diversity and lack of correlation between inbreeding
      and health.
AB  - One problem in modern dogs is a high occurrence of physical diseases, defects and
      disorders. Many breeds exhibit physical problems that affect individual dogs
      throughout life. A potential cause of these problems is inbreeding that is known
      to reduce the viability of individuals. We investigated the possible correlation
      between recent inbreeding and health problems in dogs and used studbook data from
      26 breeds provided by the Swedish Kennel Club for this purpose. The pedigrees
      date back to the mid-20th century and comprise 5-10 generations and 1 000-50 000
      individuals per pedigree over our study period of 1980-2010. We compared levels
      of inbreeding and loss of genetic variation measured in relation to the number of
      founding animals during this period in the investigated dog breeds that we
      classified as 'healthy' (11 breeds) or 'unhealthy' (15) based on statistics on
      the extent of veterinary care obtained from Sweden's four largest insurance
      companies for pets. We found extensive loss of genetic variation and moderate
      levels of recent inbreeding in all breeds examined, but no strong indication of a
      difference in these parameters between healthy versus unhealthy breeds over this
      period. Thus, recent breeding history with respect to rate of inbreeding does not
      appear to be a main cause of poor health in the investigated dog breeds in
      Sweden. We identified both strengths and weaknesses of the dog pedigree data
      important to consider in future work of monitoring and conserving genetic
      diversity of dog breeds. 

PMID- 24289537
TI  - Activation of microglia induces symptoms of Parkinson's disease in wild-type, but
      not in IL-1 knockout mice.
AB  - BACKGROUND: Parkinson's disease (PD) is an age-related progressive
      neurodegenerative disorder caused by selective loss of dopaminergic neurons from
      the substantia nigra (SN) to the striatum. The initial factor that triggers
      neurodegeneration is unknown; however, inflammation has been demonstrated to be
      significantly involved in the progression of PD. The present study was designed
      to investigate the role of the pro-inflammatory cytokine interleukin-1 (IL-1) in
      the activation of microglia and the decline of motor function using IL-1 knockout
      (KO) mice. METHODS: Lipopolysaccharide (LPS) was stereotaxically injected into
      the SN of mice brains as a single dose or a daily dose for 5 days (5 mg/2
      ml/injection, bilaterally). Animal behavior was assessed with the rotarod test at
      2 hr and 8, 15 and 22 days after the final LPS injection. RESULTS: LPS treatment
      induced the activation of microglia, as demonstrated by production of IL-1beta
      and tumor necrosis factor (TNF) alpha as well as a change in microglial
      morphology. The number of cells immunoreactive for 4-hydroxynonenal (4HNE) and
      nitrotyrosine (NT), which are markers for oxidative insults, increased in the SN,
      and impairment of motor function was observed after the subacute LPS treatment.
      Cell death and aggregation of alpha-synuclein were observed 21 and 30 days after
      the final LPS injection, respectively. Behavioral deficits were observed in wild
      type and TNFalpha KO mice, but IL-1 KO mice behaved normally. Tyrosine
      hydroxylase (TH) gene expression was attenuated by LPS treatment in wild-type and
      TNFalpha KO mice but not in IL-1 KO mice. CONCLUSIONS: The subacute injection of
      LPS into the SN induces PD-like pathogenesis and symptoms in mice that mimic the
      progressive changes of PD including the aggregation of alpha-synuclein. LPS
      induced dysfunction of motor performance was accompanied by the reduced gene
      expression of TH. These findings suggest that activation of microglia by LPS
      causes functional changes such as dopaminergic neuron attenuation in an IL-1
      dependent manner, resulting in PD-like behavioral impairment.

PMID- 24289538
TI  - Simvastatin exerts antiamnesic effect in Abeta25-35 -injected mice.
AB  - AIM AND METHODS: Simvastatin (SV) is reported to improve cognition and slow the
      progression of Alzheimer's disease (AD). This study explored the mechanisms
      underlying the antiamnesic effect of SV in AD using behavior tests, histological
      examination, western blot analysis, and electrophysiological recording technique
      in AD model mice created by intracerebroventricular injection (i.c.v.) of Abeta25
      35 . RESULTS: Chronic administration of SV (40 mg/kg/day) for 11 days after
      Abeta25-35 -injection ameliorated the impairment of acquisition performance and
      probe trail test in Morris water maze task and alternation behavior in Y maze
      task in Abeta25-35 -mice. Abeta25-35 -induced apoptosis of hippocampal CA1
      pyramidal cells and Abeta25-35 -impaired high-frequency stimulation (HFS)
      dependent long-term potentiation (LTP) induction in hippocampal Schaffer
      collaterale-CA1 synapse were rescued by SV-treatment. SV prevented Abeta25-35 
      inhibited protein kinase B (Akt) and extracellular signal-related kinase-2 (ERK2)
      phosphorylation, which was sensitive to alpha7 nicotinic acetylcholine receptor
      (alpha7nAChR) antagonist MLA. SV-induced neuroprotection was attenuated by MLA or
      phosphatidylinositol-3-kinase (PI3K) antagonist LY294002. SV-rescued LTP
      induction was blocked by alpha7nAChR, PI3K or MAPK/ERK kinase (MEK) antagonist.
      Finally, the antiamnesia of SV in Abeta25-35 -mice was attenuated by blockage of
      SV-induced neuroprotection or SV-rescued LTP induction. CONCLUSION: The
      antiamnesia of SV in Abeta25-35 -mice depends on its neuroprotection and synaptic
      plasticity improvement.

PMID- 24289539
TI  - The prevalence of diagnosed opioid abuse in commercial and Medicare managed care
      populations.
AB  - PURPOSE: To measure the prevalence of diagnosed opioid abuse and prescription
      opioid use in a multistate managed care organization. METHODS: This retrospective
      claims data analysis reviewed the prevalence of diagnosed opioid abuse and the
      parallel prevalence of prescription opioid use in half-year intervals for
      commercial and Medicare members enrolled with Humana Inc., from January 1, 2008
      to June 30, 2010. Diagnosis of opioid abuse was defined by >= 1 medical claim
      with any of the following ICD-9-CM codes: 304.0 *, 304.7 *, 305.5 *, 965.0 *,
      excluding 965.01, and opioid use was defined by >= 1 filled prescription for an
      opioid. The prevalence of opioid abuse was defined by the number of members with
      an opioid abuse diagnosis, divided by the number of members enrolled in each 6
      month interval. RESULTS: The 6-month prevalence of diagnosed opioid abuse
      increased from 0.84 to 1.15 among commercial and from 3.17 to 6.35 among Medicare
      members, per 1,000. In contrast, there was no marked increase in prescription
      opioid use during the same time period (118.0 to 114.8 for commercial members,
      240.6 to 256.9 for Medicare members, per 1,000). The prevalence of diagnosed
      opioid abuse was highest among members younger than 65 years for both genders in
      commercial (18- to 34-year-olds) and Medicare (35- to 54-year-olds) populations.
      CONCLUSIONS: Despite a stable rate of prescription opioid use among the observed
      population, the prevalence of diagnosed opioid abuse is increasing, particularly
      in the Medicare population.

PMID- 24289540
TI  - Evaluation of occupational performance and pain intensity: before and after back
      surgery and rehabilitation.
AB  - OBJECTIVE: The study had a descriptive, longitudinal design and evaluated
      occupational performance and pain intensity in daily occupations for patients
      with low back pain (LBP), assessed preoperatively, and at six and 12 months after
      surgery and rehabilitation. METHODS: Patients were assessed by surgeons and
      occupational therapists (OTs) to determine whether surgery was required. The OTs
      used the Assessment of Pain and Occupational Performance (POP) instrument. The
      POP measures 36 occupations in two dimensions: occupational performance and pain
      intensity. Patients with specific LBP (n = 97) were included. RESULTS:
      Preoperatively, 23 occupations showed lower performance and "severe pain". At six
      months, 27 occupations were performed "without restriction" (p = n.s. - < 0.001)
      and without pain or with "mild pain" (p < 0.001). A comparison of preoperative
      values with those at 12 months showed that 35 occupations were significantly
      changed on both scales, and 31 occupations were performed "without restriction"
      (p < 0.01-< 0.001) and "without pain" (p < 0.001). CONCLUSIONS: The results
      indicate significant improvements between baseline, six months, and 12 months.
      Moreover, when occupational performance and pain intensity were separately
      identified, it was shown that patients had regained their performance at an
      ordinary level without pain. This underlines the added value of differentiating
      between disability and pain.

PMID- 24289542
TI  - Animal derived products may conflict with religious patients' beliefs.
AB  - BACKGROUND: Implants and drugs with animal and human derived content are widely
      used in medicine and surgery, but information regarding ingredients is rarely
      obtainable by health practitioners. A religious perspective concerning the use of
      animal and human derived drug ingredients has not thoroughly been investigated.
      The purpose of this study was to clarify which parts of the medical and surgical
      treatments offered in western world-hospitals that conflicts with believers of
      major religions. METHODS: Religious and spiritual leaders of the six largest
      religions worldwide (18 branches) were contacted. A standardised questionnaire
      was sent out regarding their position on the use of human and animal derived
      products in medical and surgical treatments. RESULTS: Of the 18 contacted
      religious branches, 10 replied representing the 6 largest religions worldwide.
      Hindus and Sikhs did not approve of the use of bovine or porcine derived
      products, and Muslims did not accept the use of porcine derived drugs, dressings
      or implants. Christians (including Jehovah's Witnesses), Jews and Buddhists
      accepted the use of all animal and human derived products. However, all religions
      accepted the use of all these products in case of an emergency and only if
      alternatives were not available. CONCLUSIONS: The views here suggest that
      religious codes conflict with some treatment regimens. It is crucial to obtain
      informed consent from patients for the use of drugs and implants with animal or
      human derived content. However, information on the origin of ingredients in drugs
      is not always available to health practitioners.

PMID- 24289541
TI  - Identification of novel antimicrobial resistance genes from microbiota on retail
      spinach.
AB  - BACKGROUND: Drug resistance genes and their mobile genetic elements are
      frequently identified from environmental saprophytic organisms. It is widely
      accepted that the use of antibiotics in animal husbandry selects for drug
      resistant microorganisms, which are then spread from the farm environment to
      humans through the consumption of contaminated food products. We wished to
      identify novel drug resistance genes from microbial communities on retail food
      products. Here, we chose to study the microbial communities on retail spinach
      because it is commonly eaten raw and has previously been associated with
      outbreaks of bacterial infections. RESULTS: We created metagenomic plasmid
      libraries from microbiota isolated from retail spinach samples. We identified
      five unique plasmids that increased resistance to antimicrobial drugs in the E.
      coli host. These plasmids were identified in E. coli that grew on plates that
      contained ampicillin (pAMP), aztreonam (pAZT), ciprofloxacin (pCIP), trimethoprim
      (pTRM), and trimethoprim-sulfamethoxazole (pSXT). We identified open reading
      frames with similarity to known classes of drug resistance genes in the DNA
      inserts of all 5 plasmids. These drug resistance genes conferred resistance to
      fluoroquinolones, cephalosporins, and trimethoprim, which are classes of
      antimicrobial drugs frequently used to treat human Gram negative bacterial
      infections. These results show that novel drug resistance genes are found in
      microbiota on retail produce items. CONCLUSIONS: Here we show that microbiota of
      retail spinach contains DNA sequences previously unidentified as conferring
      antibiotic resistance. Many of these novel sequences show similarity to genes
      found in species of bacteria, which have previously been identified as commensal
      or saprophytic bacteria found on plants. We showed that these resistance genes
      are capable of conferring clinically relevant levels of resistance to
      antimicrobial agents. Food saprophytes may serve as an important reservoir for
      new drug-resistance determinants in human pathogens.

PMID- 24289543
TI  - Do the different reasons for lactation discontinuation have similar impact on
      future breast problems?
AB  - BACKGROUND: Breast feeding is considered to be mutually beneficial for both
      mothers and infants, though the effect of lactation problems on development of
      breast lesions (whether benign or malignant) is not clear. OBJECTIVES: This study
      was conducted to identify possible relations between lactation problems and
      benign and malignant breast disease. MATERIALS AND METHODS: 308 patients referred
      to two referral breast clinics in Tehran, the capital city of IR Iran, between
      January 2008 and January 2011, were recruited. They were interviewed by a
      standard questionnaire regarding breast feeding problems. The study population
      was classified in 3 major groups; breast feeding without any problem,
      unwillingness to breast feed according to whether mothers' preference not to feed
      or some breast problems like mastitis, and finally insufficient milk that caused
      the mothers to feed their babies with formula. RESULTS: Recruiting binary
      logistic regression method, mother's unwillingness to feed her child by breast
      milk, and also breast problems such as mastitis and abscess during lactation
      period showed significant relation with both benign and malignant breast diseases
      (p value<0.01). Surprisingly, inadequate milk was not associated with any of
      these conditions. CONCLUSIONS: We concluded that lactation problems which involve
      normal milk drainage from the breast may play an important role in whether the
      mother wll subsequently develope both benign and malignant pathologies. In
      contrast in the situation that the production of the milk is not sufficient and
      there are no intentional or unintentional problems in drainage of the produced
      milk, future problems would not be more common.

PMID- 24289544
TI  - Dietary non-nutritive factors in targeting of regulatory molecules in colorectal
      cancer: an update.
AB  - Colorectal cancer (CRC), a complex multi-step process involving progressive
      disruption of homeostatic mechanisms controlling intestinal epithelial
      proliferation/inflammation, differentiation, and programmed cell death, is the
      third most common malignant neoplasm worldwide. A number of promising targets
      such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related
      factor 2 (Nrf2), Wnt/beta-catenin, Notch and apoptotic signaling have been
      identified by researchers as useful targets to prevent or therapeutically inhibit
      colon cancer development. In this review article, we aimed to explore the current
      targets available to eliminate colon cancer with an update of dietary and non
      nutritional compounds that could be of potential use for interaction with
      regulatory molecules to prevent CRC. 

PMID- 24289545
TI  - Herbal remedies for combating irradiation: a green anti-irradiation approach.
AB  - Plants play important roles in human life not only as suppliers of oxygen but
      also as a fundamental resource to sustain the human race on this earthly plane.
      Plants also play a major role in our nutrition by converting energy from the sun
      during photosynthesis. In addition, plants have been used extensively in
      traditional medicine since time immemorial. Information in the biomedical
      literature has indicated that many natural herbs have been investigated for their
      efficacy against lethal irradiation. Pharmacological studies by various groups of
      investigators have shown that natural herbs possess significant radioprotective
      activity. In view of the immense medicinal importance of natural product based
      radioprotective agents, this review aims at compiling all currently available
      information on radioprotective agents from medicinal plants and herbs, especially
      the evaluation methods and mechanisms of action. In this review we particularly
      emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action
      and toxicology. We also describe modern techniques for evaluating herbal samples
      as radioprotective agents. The usage of herbal remedies for combating lethal
      irradiation is a green anti- irradiation approach for the betterment of human
      beings without high cost, side effects and toxicity. 

PMID- 24289546
TI  - Epidemiology of oral cancer in Asia in the past decade--an update (2000-2012).
AB  - The prevalence of oral cancers (OC) is high in Asian countries, especially in
      South and Southeast Asia. Asian distinct cultural practices such as betel-quid
      chewing, and varying patterns of tobacco and alcohol use are important risk
      factors that predispose to cancer of the oral cavity. The aim of this review is
      to provide an update on epidemiology of OC between 2000 and 2012. A literature
      search for this review was conducted on Medline for articles on OC from Asian
      countries. Some of the articles were also hand searched using Google. High
      incidence rates were reported from developing nations like India, Pakistan,
      Bangladesh, Taiwan and Sri Lanka. While an increasing trend has been observed in
      Pakistan, Taiwan and Thailand, a decreasing trend is seen in Philippines and Sri
      Lanka. The mean age of occurrence of cancer in different parts of oral cavity is
      usually between 51-55 years in most countries. The tongue is the leading site
      among oral cancers in India. The next most common sites in Asian countries
      include the buccal mucosa and gingiva. The 5 year survival rate has been low for
      OC, despite improvements in diagnosis and treatment. Tobacco chewing, smoking and
      alcohol are the main reasons for the increasing incidence rates. Low
      socioeconomic status and diet low in nutritional value lacking vegetables and
      fruits contribute towards the risk. In addition, viral infections, such as HPV
      and poor oral hygiene, are other important risk factors. Hence, it is important
      to control OC by screening for early diagnosis and controlling tobacco and
      alcohol use. It is also necessary to have cancer surveillance at the national
      level to collect and utilise data for cancer prevention and control programs. 

PMID- 24289547
TI  - Cancer stem cells in head and neck squamous cell carcinoma: a review.
AB  - Research indicates that a small population of cancer cells is highly tumorigenic,
      endowed with the capacity for self-renewal, and has the ability to differentiate
      into cells that constitute the bulk of tumors. These cells are considered the
      "drivers" of the tumorigenic process in some tumor types, and have been named
      cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be
      involved in the process leading to the acquisition of stemness by epithelial
      tumor cells. Through this process, cells acquire an invasive phenotype that may
      contribute to tumor recurrence and metastasis. CSC have been identified in human
      head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and
      CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer
      stem cells reside primarily in perivascular niches in the invasive fronts where
      endothelial-cell initiated events contribute to their survival and function.
      Clinically, CSC enrichment has been shown to be enhanced in recurrent disease,
      treatment failure and metastasis. CSC represent a novel target of study given
      their slow growth and innate mechanisms conferring treatment resistance. Further
      understanding of their unique phenotype may reveal potential molecular targets to
      improve therapeutic and survival outcomes in patients with HNSCC. Here, we
      discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with
      a focus on the impact of these cells on head and neck tumor progression,
      metastasis and recurrence due to treatment failure. 

PMID- 24289548
TI  - Endometriosis, leiomyoma and adenomyosis: the risk of gynecologic malignancy.
AB  - The aim of this review article was to evaluate the relationship and the possible
      etiological mechanisms between endometriosis, leiomyoma (LM) and adenomyosis and
      gynecological cancers, such as ovarian and endometrial cancer and leiomyosarcoma
      (LMS). MEDLINE was searched for all articles written in the English literature
      from July 1966 to May 2013. Reports were collected systematically and all the
      references were also reviewed. Malignant transformation of gynecologic benign
      diseases such as endometriosis, adenomyosis and LM to ovarian and endometrial
      cancer remains unclear. Hormonal factors, inflammation, familial predisposition,
      genetic alterations, growth factors, diet, altered immune system, environmental
      factors and oxidative stress may be causative factors in carcinogenesis. Early
      menarche, low parity, late menopause and infertility have also been implicated in
      the pathogenesis of these cancers. Ovarian cancers and endometriosis have been
      shown to have common genetic alterations such as loss of heterozygosity (LOH),
      PTEN, p53, ARID1A mutations. MicroRNAs have also been implicated in malignant
      transformation. Inflammation releases proinflammatory cytokines, and activates
      tumor associated macrophages (TAMS) and nuclear factor kappa b (NF-KB) signaling
      pathways that promote genetic mutations and carcinogenesis. MED12 mutations in LM
      and smooth muscle tumors of undetermined malignant potential (STUMP) may
      contribute to malignant transformation to LMS. A hyperestrogenic state may be
      shared in common with pathogenesis of adenomyosis, LM and endometrial cancer.
      However, the effect of these benign gynecologic diseases on endometrial cancer
      should be studied in detail. This review study indicates that endometriosis, LM,
      adenomyosis may be associated with increased risk of gynecological cancers such
      as endometrial and ovarian cancers. The patients who have these gynecological
      benign diseases should be counseled about the future risks of developing cancer.
      Further studies are needed to investigate the relationship between STUMPs, LMS
      and LM and characteristics and outcome endometrial carcinoma in adenomyotic
      patients. 

PMID- 24289549
TI  - Biotransformation, a promising technology for anti-cancer drug development.
AB  - With the high morbidity and mortality caused by cancer, finding new and more
      effective anti-cancer drugs is very urgent. In current research,
      biotransformation plays a vital role in the research and development of cancer
      drugs and has obtained some achievements. In this review, we have summarized four
      applications as follows: to exploit novel anti-cancer drugs, to improve existing
      anti-cancer drugs, to broaden limited anti-cancer drug resources and to
      investigate correlative mechanisms. Three different groups of important anti
      cancer compounds were assessed to clarify the current practical applications of
      biotransformation in the development of anti-cancer drugs. 

PMID- 24289550
TI  - Genes and SNPs associated with non-hereditary and hereditary colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is the third most common cancer in both men and
      women in the world and the second leading cause of cancer-related deaths. The
      incidence of colorectal cancer has increased in Iran in the past three decades
      and is now considered as a serious problem for our society. This cancer has two
      types hereditary and non-hereditary, 80% of cases being the latter. Considering
      that the relationship between SNPs with diseases is a concern, many researchers
      believed that they offer valuable markers for identifying genes responsible for
      susceptibility to common diseases. In some cases, they are direct causes of human
      disease. One SNP can increase risk of cancer, but when considering the rate of
      overlap and frequency of DNA repair pathways, it might be expected that SNP alone
      cannot affect the final result of cancer, although several SNPs together can
      exert a significant influence. Therefore identification of these SNPs is very
      important. The most important loci which include mutations are: MLH1, MSH2, PMS2,
      APC, MUTYH, SMAD7, STK11, XRCC3, DNMT1, MTHFR, Exo1, XRCC1 and VDR. Presence of
      SNPs in these genes decreases or increases risk of colorectal cancer. MATERIALS
      AND METHODS: In this article we reviewed the Genes and SNPs associated with non
      hereditary and hereditary of colorectal cancer that recently were reported from
      candidate gene y, meta-analysis and GWAS studies. RESULTS: As with other cancers,
      colorectal cancer is associated with SNPs in gene loci. Generally, by exploring
      SNPs, it is feasible to predict the risk of developing colorectal cancer and thus
      establishing proper preventive measures. CONCLUSIONS: SNPs of genes associated
      with colorectal cancer can be used as a marker SNP panel as a potential tool for
      improving cancer diagnosis and treatment planning.

PMID- 24289551
TI  - Prognostic involvement of nucleophosmin mutations in acute myeloid leaukemia.
AB  - Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a
      molecular chaperone and is mostly found in nucleoli. NPM also involved in the
      maturation of preribosomes and duplication of centrosomes. Furthermore, it is
      also active in control and regulation of the ARF-p53 tumor suppressor pathway. A
      high rate of incidence and prognostic involvement is reported by various authors
      in AML patients. In AML it behaves as a favorable prognostic marker. NPM
      mutations are more frequently associated with normal-karyotype AML and are
      usually absent in patients having abnormal or poor cytogenetic. NPM mutations are
      not frequent in other hematopoietic tumors .Two main types of mutations have been
      described to date. Both of these cause abnormal cytoplasmic localization of NPM1.
      Their high incidence rate in normal karyoptype and their favorable nature make
      those mutations hot spot or front face mutations which should be checked before
      treatment starts. 

PMID- 24289552
TI  - Incidence and mortality from mucosal head and neck cancers amongst Australian
      states and territories: what it means for the northern territory.
AB  - Mucosal head and neck cancers are squamous cell carcinomas that develop in the
      upper-aero digestive epithelium. Together they constitute the sixth most common
      cancer with an estimated 900,000 new cases and 350,000 deaths each year reported
      worldwide. The risk factors are tobacco, alcohol and human papillomavirus (HPV).
      Our research team initially reported a high incidence rate of HNC in the
      indigenous population of the Northern Territory. Mortality rates also vary in the
      Australian States and Territories, with particularly high mortality observed in
      the Northern Territory. There is a paucity of incidence studies of HNC for the
      Australian States and Territories. Therefore this review primarily focuses on
      variation in incidence and mortality iacross the country and highlights
      specifically the high incidence and mortality in the Northern Territory.
      Attention is also given to sex-specific incidence and mortality rates. 

PMID- 24289553
TI  - Epidemiology, major risk factors and genetic predisposition for breast cancer in
      the Pakistani population.
AB  - Occurrence of breast cancer is related to genetic as well as cultural,
      environmental and life-style factors. Variations in diversity of these factors
      among different ethnic groups and geographical areas emphasize the immense need
      for studies in all racial-ethnic populations. The incidence of breast cancer in
      Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that
      in neighboring countries like Iran and India, accounting for 34.6% of female
      cancers. The Pakistani population is deficient in information regarding breast
      cancer etiology and epidemiology, but efforts done so far had suggested
      consanguinity as a major risk factor for frequent mutations leading to breast
      cancer and has also shed light on genetic origins in different ethnic groups
      within Pakistan. World-wide research efforts on different ethnicities have
      enhanced our understanding of genetic predisposition to breast cancer but despite
      these discoveries, 75% of the familial risk of breast cancer remains unexplained,
      highlighting the fact that the majority of breast cancer susceptibility genes
      remain unidentified. For this purpose Pakistani population provides a strong
      genetic pool to elucidate the genetic etiology of breast cancer because of cousin
      marriages. In this review, we describe the known breast cancer predisposition
      factors found in the local Pakistani population and the epidemiological research
      work done to emphasize the importance of exploring factors/variants contributing
      to breast cance, in order to prevent, cure and decrease its incidence in our
      country. 

PMID- 24289554
TI  - Radiation-induced Cochlea hair cell death: mechanisms and protection.
AB  - Cochlea hair cell death is regarded to be responsible for the radiation-induced
      sensorineural hearing loss (SNHL), which is one of the principal complications of
      radiotherapy (RT) for head and neck cancers. In this mini- review, we focus on
      the current progresses trying to unravel mechanisms of radiation-induced hair
      cell death and find out possible protection. P53, reactive oxygen species (ROS)
      and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the
      processes leading to radiation hair cell death. Potential protectants, such as
      amifostine, N-acetylcysteine (NAC) and epicatechin (EC) , are claimed to be
      effective at reducing radiation- inducedhair cell death. The RT dosage, selection
      and application of concurrent chemotherapy should be pre- examined in order to
      minimize the damage to cochlea hair cells. 

PMID- 24289555
TI  - Involvement of EBV-encoded BART-miRNAs and dysregulated cellular miRNAs in
      nasopharyngeal carcinoma genesis.
AB  - The definite molecular mechanisms underlying the genesis of nasopharyngeal
      carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding
      RNAs which are implicated in cell proliferation, apoptosis, and even
      carcinogenesis through negatively regulating gene expression post
      transcriptionally. EBV was the first human virus found to express miRNAs. EBV
      encoded BART-miRNAs and dysregulated cellular miRNAs are involved in
      carcinogenesis of NPC by interfering in the expression of viral and host cell
      genes related to immune responses and perturbing signal pathways of
      proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy
      sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular
      miRNAs will provide new insights concerning the complicated gene regulated
      network and shed light on novel strategies for the diagnosis, therapy and
      prognosis of NPC. 

PMID- 24289556
TI  - Targeting SHCBP1 inhibits cell proliferation in human hepatocellular carcinoma
      cells.
AB  - Src homology 2 domain containing (SHC) is a proto-oncogene which mediates cell
      proliferation and carcinogenesis in human carcinomas. Here, the SHC SH2-domain
      binding protein 1 (SHCBP1) was first established to be up-regulated in human
      hepatocellular carcinoma (HCC) tissues by array-base comparative genome
      hybridization (aCGH). Meanwhile, we examine and verify it by quantitative real
      time PCR and western blot. Our current data show that SHCBP1 was up-regulated in
      HCC tissues. Overexpression of SHCBP1 could significantly promote HCC cell
      proliferation, survival and colony formation in HCC cell lines. Furthermore,
      knockdown of SHCBP1 induced cell cycle delay and suppressed cell proliferation.
      Furthermore, SHCBP1 could regulate the expression of activate extracellular
      signal-regulated kinase 1/2 (ERK1/2) and cyclin D1. Together, our findings
      indicate that SHCBP1 may contribute to human hepatocellular carcinoma by
      promoting cell proliferation and may serve as a molecular target of cancer
      therapy. 

PMID- 24289557
TI  - Clinical significance of soluble major histocompatibility complex class I chain
      related a in renal cell carcinoma patients.
AB  - OBJECTIVE: Major histocompatibility complex class I chain-related A (MICA) is a
      stress-inducible glycoprotein that can be shed as a soluble protein. This study
      was conducted to determine the expression of MICA in renal cell carcinoma (RCC)
      and examine the clinical relevance of soluble MICA (sMICA) in this disease.
      METHODS: Immunohistochemistry and real-time PCR analyses were performed to assess
      the expression of MICA in 48 pairs of RCC and adjacent normal renal tissues.
      Serum levels of sMICA were measured in 48 RCC patients, 12 patients with benign
      renal tumors, and 20 healthy individuals. The correlations between sMICA levels
      and clinicopathological parameters were analyzed and the diagnostic performance
      of sMICA in RCC was evaluated. RESULTS: RCCs exhibited elevated expression of
      MICA compared to adjacent normal tissues. Serum concentrations of sMICA were
      significantly greater in RCC patients (348.5 +/- 32.5 pg/ml) than those with
      benign disease (289.3 +/- 30.4 pg/ml) and healthy controls (168.4 +/- 43.2 pg/ml)
      and significantly correlated with advanced tumor stage, lymph node metastasis,
      distant metastasis, vascular invasion, and higher histological grade. Using a cut
      off point of 250 pg/ml, sMICA demonstrated a specificity and sensitivity of 63.2%
      and 75.6%, respectively, in distinguishing between RCC and benign renal tumors.
      CONCLUSION: MICA expression is upregulated in RCC and increased serum sMICA
      levels predict aggressive tumor behavior. However, the applicability of sMICA
      alone is limited in distinguishing RCC from benign renal tumors.

PMID- 24289558
TI  - Lifestyle factors including diet and leukemia development: a case-control study
      from Mumbai, India.
AB  - In India, among males, leukemia rates vary across the country. The present
      unmatched hospital-based case- control study conducted at Tata Memorial Hospital
      included subjects registered between the years 1997-99. There were 246 leukemia
      cases and 1,383 normal controls. Data on demographics, lifestyle, diet and
      occupation history were recorded. Cigarette (OR=2.1) and bidi smoking (OR=3.4)
      showed excess risk for leukemia. Odds ratios were 3.9 for fish-eaters, 0.40 for
      chilli eaters, 1.5 for milk drinkers and 0.60 for coffee drinkers, compared to
      non-drinkers/eaters. However, neither exposure to use of pesticides nor cotton
      dust showed any excess risk for leukemia. 

PMID- 24289559
TI  - Triptolide inhibits histone methyltransferase EZH2 and modulates the expression
      of its target genes in prostate cancer cells.
AB  - The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical
      roles in prostate cancer (PCa) development and is a potential target for PCa
      treatment. Triptolide possesses anti-tumor activity, but it is unknown whether
      its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a
      target for Triptolide in PCa cells. Our data showed that Triptolide suppressed
      PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2
      attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide
      treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2,
      CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA
      levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the
      PCa cell growth inhibition mediated by Triptolide might be associated with
      downregulation of EZH2 expression and the subsequent modulation of target genes. 

PMID- 24289560
TI  - Lack of association of BRCA1 and BRCA2 variants with breast cancer in an ethnic
      population of Saudi Arabia, an emerging high-risk area.
AB  - Incidence of breast cancer shows geographical variation, even within areas of
      ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of
      breast cancer in its unexplored ethnic populations over the past few years. We
      aimed at determining whether any association exists between single nucleotide
      polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer
      associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time
      Polymerase chain reaction genotyping assays were used to determine the frequency
      of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a
      group of 100 breast cancer patients and unaffected age matched controls of Saudi
      Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2
      studied variant show any significant association with the disease. This study
      failed to find any role of the concerned variants in breast cancer either as risk
      or as prognostic factors. The small number of patients registered was one of the
      limitations of this study. In summary, comparison of mutation profile with other
      ethnic populations and regions reflected both differences and similarities
      indicating co-exposure to a unique set of risk factors. The differences could be
      due to exposure to particular environmental carcinogens; different lifestyle,
      reproductive pattern; dietary or cultural practices of Saudi Arabian women that
      need further investigations. 

PMID- 24289561
TI  - Expression characteristics of proteins of the insulin-like growth factor axis in
      non-small cell lung cancer patients with preexisting type 2 diabetes mellitus.
AB  - BACKGROUND: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and
      mortality of patients with some cancers. Insulin like growth factor (IGF) and
      insulin receptor (IR) signaling axes play important roles in both cancer and
      diabetes development. We aimed to explore the expression characteristics of
      proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with
      preexisting T2DM. METHODS: Fifty-five NSCLC patients with preexisting T2DM were
      retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio.
      The expression of proteins in IGF/IR axis was detected by immunohistochemical
      staining. Clinicopathological data were collected to analyze their relationship
      with the protein expression. RESULTS: Both IGF 1 receptor (IGF-1R) and insulin
      receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM
      group, compared with those without T2DM. The high expression of IGF-1R and IRS-2
      were found to be negatively associated with lymph node metastases and T staging
      in the T2DM group, respectively, and IRS-2 expression was also found more in the
      subgroup whose T2DM duration was more than 4 years. No difference was detected in
      the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or
      without T2DM. CONCLUSION: Our study found higher expression of IGF-1R and IRS-2
      proteins in NSCLC patients with preexisting T2DM, and that there was an
      association with early stage NSCLC, which suggested that IGF signaling may play
      an important early event in development of NSCLC associated with diabetes.

PMID- 24289562
TI  - Comparison of male and female breast cancer incidence and mortality trends in
      Central Serbia.
AB  - BACKGROUND: To compare breast cancer incidence and mortality trends in Central
      Serbia between males and females in the period 1999-2009. MATERIALS AND METHODS:
      In this descriptive study, mortality data were obtained from the National
      Statistics Institute and morbidity data were derived from Institute of Public
      Health of Serbia for the period of interest. RESULTS: Breast cancer is a leading
      cancer in the female population of Central Serbia, whereas in male population it
      is not on the list of 10 leading localizations, concerning both incidence as well
      as mortality. In the period 1999-2009 the average standardized incidence rates of
      breast cancer were 60.5/100,000 in women and 1.4/100,000 in men, while average
      standardized mortality rates were 20.4/100,000 and 0.4/100,000. The average
      standardized incidence and mortality rates were about 45 times higher in females
      than males. Male breast cancer comprises approximately 2.1% of all breast cancer
      cases. The average age-specific mortality and incidence rates increased with age
      in both sexes. In the observed period standardized mortality rates of breast
      cancer increased significantly only in men (y=0.320+0.021?, p=0.044).
      CONCLUSIONS: The increase of breast cancer incidence in both sexes and mortality
      in men, indicate an urgent need for Serbian health professionals to apply
      existing cancer control and preventive measures. Male breast cancer is more
      present than in other world regions, with an outstanding increase of mortality,
      which demands a timely identification (screening) and adequate treatment. A
      national policy including mammography should be considered in the light of the
      newest findings.

PMID- 24289563
TI  - PKC?-dependent activation of the ubiquitin proteasome system is responsible for
      high glucose-induced human breast cancer MCF-7 cell proliferation, migration and
      invasion.
AB  - Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer
      development over the past decades. However, the mechanism underlying this
      contribution is poorly understood. In this study, we determined that high glucose
      enhanced proteasome activity was accompanied by enhanced proliferation, migration
      and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7
      cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose
      induced MCF-7 cell growth and invasion. Furthermore, high glucose increased
      protein kinase C delta (PKC?)-phosphorylation. Administration of the specific
      PKC? inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth
      and invasion. In addition, PKC? inhibition by both rottlerin and PKC? shRNA
      significantly suppressed high glucose-induced proteasome activity. Our results
      suggest that PKC?-dependent ubiquitin proteasome system activation plays an
      important role in high glucose- induced breast cancer cell growth and metastasis.

PMID- 24289564
TI  - Changes in the attitudes and behavior of relatives of breast cancer patients
      concerning cancer prevention and screening.
AB  - BACKGROUND: Changes in the attitudes and behavior of relatives of breast cancer
      patients concerning cancer prevention and screening after diagnosis in a loved
      one were evaluated. MATERIALS AND METHODS: Forty-three questions were used to
      collect data from the relatives of the breast cancer patients who had been living
      with their relatives for at least one year. RESULTS: The study group was composed
      of 171 female relatives (median age: 43, range: 17-82 yr). After the patients
      were diagnosed with breast cancer, changes in the attitudes and behavior of their
      relatives toward the prevention and screening of cancer were evident in 78
      (45.6%) of the study participants (e.g. eating habits, quit or reduced smoking ,
      exercise habits). In addition, it was noted that some characteristics of the
      relatives had different effects on different attitudes and behavior. CONCLUSIONS:
      Awareness on breast cancer among the relatives of breast cancer patients is
      useful for the management of health and social problems that can be seen in these
      individuals. At the same time, this information could help countries determine
      whether their actual level of healthcare for early cancer diagnosis, prevention,
      and screening are adequate.

PMID- 24289565
TI  - Clinical observation of whole brain radiotherapy concomitant with targeted
      therapy for brain metastasis in non-small cell lung cancer patients with
      chemotherapy failure.
AB  - OBJECTIVE: To investigate the clinical effects of whole brain radiotherapy
      concomitant with targeted therapy for brain metastasis in non-small cell lung
      cancer (NSCLC) patients with chemotherapy failure. MATERIALS AND METHODS: Of the
      157 NSCLC patients with chemotherapy failure followed by brain metastasis
      admitted in our hospital from January 2009 to August 2012, the combination group
      (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy
      while the radiotherapy group (92 cases) were given whole brain radiotherapy only.
      Short-term effects were evaluated based on the increased MRI in brain 1 month
      after whole brain radiotherapy. Intracranial hypertension responses,
      hematological toxicity reactions and clinical effects of both groups were
      observed. RESULTS: There were more adverse reactions in the combination group
      than in radiotherapy group, but no significant differences were observed between
      the two groups in response rate (RR) and disease control rate (DCR) (P>0.05).
      Medium progression free survival (PFS), medium overall survival (OS) and 1-year
      survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while
      in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%,
      respectively, which indicated that there were significant differences in PFS and
      OS between the two groups (P<0.05). Additionally, RPA grading of each factor in
      the combination group was a risk factor closely related with survival, with
      medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months,
      and OS being 3.6 months and 6.3 months, respectively. CONCLUSIONS: Whole brain
      radiotherapy concomitant with target therapy is favorable for adverse reaction
      tolerance and clinical effects, being superior in treating brain metastasis in
      NSCLC patients with chemotherapy failure and thus deserves to be widely applied
      in the clinic.

PMID- 24289566
TI  - Teratoma formation in immunocompetent mice after syngeneic and allogeneic
      implantation of germline capable mouse embryonic stem cells.
AB  - BACKGROUND: Embryonic stem cells (ESCs) have the potential to form teratomas when
      implanted into immunodeficient mice, but data in immunocompetent mice are
      limited. We therefore investigated teratoma formation after implantation of three
      different mouse ESC (mESC) lines into immunocompetent mice. MATERIALS AND
      METHODS: BALB/c mice were injected with three highly germline competent mESCs
      (129Sv, BALB/c and C57BL/6) subcutaneously or under the kidney capsule. After 4
      weeks, mice were euthanized and examined histologically for teratoma development.
      The incidence, size and composition of teratomas were compared using Pearson Chi
      square, t-test for dependent variables, one-way analysis of variance and the
      nonparametric Kruskal- Wallis analysis of variance and median test. RESULTS:
      Teratomas developed from all three cell lines. The incidence of formation was
      significantly higher under the kidney capsule compared to subcutaneous site and
      occurred in both allogeneic and syngeneic mice. Overall, the size of teratoma was
      largest with the 129Sv cell line and under the kidney capsule. Diverse embryonic
      stem cell-derived tissues, belonging to the three embryonic germ layers, were
      encountered, reflecting the pluripotency of embryonic stem cells. Most commonly
      represented tissues were nervous tissue, keratinizing stratified squamous
      epithelium (ectoderm), smooth muscle, striated muscle, cartilage, bone
      (mesoderm), and glandular tissue in the form of gut- and respiratory-like
      epithelia (endoderm). CONCLUSIONS: ESCs can form teratomas in immunocompetent
      mice and, therefore, removal of undifferentiated ESC is a pre-requisite for a
      safe use of ESC in cell-based therapies. In addition the genetic relationship of
      the origin of the cell lines to the ability to transplant plays a major role.

PMID- 24289567
TI  - DNMT3a rs1550117 polymorphism association with increased risk of Helicobacter
      pylori infection.
AB  - BACKGROUND: DNA methyltransferase-3a (DNMT3a) plays significant roles in
      embryogenesis and the generation of aberrant methylation in carcinogenesis. This
      study aimed to investigate associations between single nucleotide polymorphisms
      (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric
      atrophy and gastric cancer. METHODS: The subjects comprised 447 patients with
      gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls.
      Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman
      assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by
      tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were
      calculated by multivariate logistic regression. RESULTS: Among healthy controls,
      risk of H.pylori infection was significantly higher in subjects with the
      rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08,
      (95%CI: 1.02-4.32)]. However, no significant correlation was found between the
      two SNPs and risk of developing gastric atrophy or gastric cancer. In addition,
      no increase in DNMT3a expression was observed in the gastric cancer with H.pylori
      infection. CONCLUSIONS: This study revealed that DNMT3a rs1550117 polymorphism is
      significantly associated with an increased risk of H. pylori infection, but did
      not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to
      either gastric atrophy or gastric cancer. The biological roles of DNMT3a
      polymorphisms require further investigation.

PMID- 24289568
TI  - Anticancer activity of Petroselinum sativum seed extracts on MCF-7 human breast
      cancer cells.
AB  - Pharmacological and preventive properties of Petroselinum sativum seed extracts
      are well known, but the anticancer activity of alcoholic extracts and oil of
      Petroselinum sativum seeds on human breast cancer cells have not been explored so
      far. Therefore, the present study was designed to investigate the cytotoxic
      activities of these extracts against MCF-7 cells. Cells were exposed to 10 to
      1000 MUg/ml of alcoholic seed extract (PSA) and seed oil (PSO) of Petroselinum
      sativum for 24 h. Post-treatment, percent cell viability was studied by 3-(4, 5
      dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red
      uptake (NRU) assays, and cellular morphology by phase contrast inverted
      microscopy. The results showed that PSA and PSO significantly reduced cell
      viability, and altered the cellular morphology of MCF-7 cells in a concentration
      dependent manner. Concentrations of 50 MUg/ml and above of PSA and 100 MUg/ml and
      above of PSO were found to be cytotoxic in MCF-7 cells. Cell viability at 50,
      100, 250, 500 and 1000 MUg/ml of PSA was recorded as 81%, 57%, 33%, 8% and 5%,
      respectively, whereas at 100, 250, 500, and 1000 MUg/ml of PSO values were 90%,
      78%, 62%, and 8%, respectively by MTT assay. MCF-7 cells exposed to 250, 500 and
      1000 MUg/ml of PSA and PSO lost their typical morphology and appeared smaller in
      size. The data revealed that the treatment with PSA and PSO of Petroselinum
      sativum induced cell death in MCF-7 cells. 

PMID- 24289569
TI  - Involvement of cdc25c in cell cycle alteration of a radioresistant lung cancer
      cell line established with fractionated ionizing radiation.
AB  - Cancer patients often suffer from local tumor recurrence after radiation therapy.
      Cell cycling, an intricate sequence of events which guarantees high genomic
      fidelity, has been suggested to affect DNA damage responses and eventual
      radioresistant characteristics of cancer cells. Here, we established a
      radioresistant lung cancer cell line, A549R , by exposing the parental A549 cells
      to repeated gamma-ray irradiation with a total dose of 60 Gy. The
      radiosensitivity of A549 and A549R was confirmed using colony formation assays.
      We then focused on examination of the cell cycle distribution between A549 and
      A549R and found that the proportion of cells in the radioresistant S phase
      increased, whereas that in the radiosensitive G1 phase decreased. When A549 and
      A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle
      redistribution suggested that G2-M cell cycle arrest plays a predominant role in
      mediating radioresistance. In order to further explore the possible mechanisms
      behind the cell cycle related radioresistance, we examined the expression of
      Cdc25 proteins which orchestrate cell cycle transitions. The results showed that
      expression of Cdc25c increased accompanied by the decrease of Cdc25a and we
      proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a,
      determines the radioresistance of cells. 

PMID- 24289570
TI  - Improved detection of metastases by step sectioning and immuno-histochemical
      staining of axillary sentinel nodes in patients with breast carcinoma.
AB  - BACKGROUND: The object of this study was to examine whether a new protocol
      including step-sectioning and immunohistochemistry (IHC) staining of axillary
      sentinel nodes (SN) would lead to detection of more metastases in patients with
      breast cancer. MATERIALS AND METHODS: Sixty-nine tumor free sentinel lymph nodes
      were examined. Step frozen sectioning was performed on formalin fixed SN and
      stained both by hematoxylin and eosin (H and E) and cytokeratin markers using
      IHC. Any tumoral cell in IHC stained slides were considered as a positive result.
      Metastases up to 0.2 mm were considered as isolated tumor cells and 0.2 up to 2
      mm as micrometastasis. RESULTS: Mean age of the patients was 48.7+/-12.2 years.
      Step sectioning of the SN revealed 11 involved by metastasis which was
      statistically significant (p<0.001). Furthermore, 15 (21.7%) of the patients
      revealed positive results in IHC staining for pan-CK marker and this was also
      statistically significant (p=0.001). Ten patients had tumoral involvement in
      lymph nodes harvested from axillary dissection and 4 out of 15 lymph nodes with
      positive result for CK marker were isolated tumor cells. However, 4 of 10
      patients with tumor positive lymph nodes in axillary dissection were negative for
      CK marker and in contrast 6 of the pan-CK positive SN were in patients with tumor
      free axillary lymph nodes. CONCLUSIONS: Both IHC and step sectioning improve the
      detection rate of metastases. Considering the similar power of these two methods,
      we recommend using either IHC staining or step sectioning for better evaluation
      of harvested SNs.

PMID- 24289571
TI  - Prognostic role of C-reactive protein in gastric cancer: a meta-analysis.
AB  - BACKGROUND: A number of studies have investigated the association between
      increased pretreatment serum C-reactive protein (CRP) levels and the prognosis of
      gastric cancer. However, due to the inconsistent results, whether the serum CRP
      level can be a prognostic factor in primary gastric cancer remains controversial.
      METHODS: We searched Medline, PubMed, Embase and the Cochrane Central Register of
      Controlled Trials for relevant high-quality reports. A meta-analysis was carried
      out using the included studies to assess the association between pretreatment
      serum CRP level and overall survival (OS) in patients with gastric cancer.
      Correlation analyses were conducted to evaluate the relationship between serum
      CRP and tumor characteristics such as tumor node metastasis (TNM) stage and
      recurrence. RESULTS: Twelve reports involving 2,597 patients with gastric cancer
      were included. Primary meta-analysis indicated a significant association between
      elevated CRP level and poor OS (HR 1.77, 95% CI 1.56-2.00). Subgroup analyses
      showed no single factor could alter the primary results when we divided the
      included studies by "number of patients", "max follow-up period", "TNM stage",
      "treatment" and "cut-off value". Correlation analyses showed that serum CRP level
      was significantly related to TNM stage (OR 2.96, 95% CI 2.22-3.93) and tumor
      recurrence (OR 1.81, 95% CI 1.21-2.71). CONCLUSIONS: We demonstrated that
      increased pretreatment serum CRP level (>=10mg/L) was significantly associated
      with poor prognosis in gastric cancer patients, either in early or advanced
      stages.

PMID- 24289572
TI  - Evidence of multimeric forms of HSP70 with phosphorylation on serine and tyrosine
      residues--implications for roles of HSP70 in detection of GI cancers.
AB  - BACKGROUND: Heat-shock protein70 (HSP70) are intracellular protein chaperones,
      with emerging evidence of their association with various diseases. We have
      previously reported significantly elevated plasma-HSP70 (pHSP70) in pancreatic
      cancer. Current methods of pHSP70 isolation are ELISA-based which lack
      specificity due to cross-reactivity by similarities in the amino-acid sequence in
      regions of the protein backbone resulting in overestimated HSP70 value. MATERIALS
      AND METHODS: This study was undertaken to develop a methodology to capture all
      isoforms of pHSP70, while further defining their tyrosine and serine
      phosphorylation status. RESULTS: The methodology included gel electrophoresis on
      centrifuged supernatant obtained from plasma incubated with HSP70 antibody
      coupled beads. After blocking non-specific binding sites, blots were
      immunostained with monoclonal-antibody specific for human-HSP70, phosphoserine
      and phosphotyrosine. CONCLUSIONS: Our novel immunocapture approach has distinct
      advantages over the commercially available methods of pHSP70 quantification by
      allowing isolation of molecular aggregates of HSP70 with additional ability to
      precisely distinguish phosphorylation state of HSP70 molecules at serine and
      tyrosine residues.

PMID- 24289573
TI  - Golgi phosphoprotein 2 down-regulates the Th1 response in human gastric cancer
      cells by suppressing IL-12A.
AB  - Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of
      diseases. Its biological function is not clear, particularly in gastric cancer.
      To investigate the role of GOLPH2 in human gastric cancer, and determine its
      effect on the Th1 lymphocyte response, its expression and that of IL-12A were
      measured by real-time PCR and immunohistochemistry. The relationship between
      GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1
      lymphocyte response was investigated with an in vitro co-culture system. The
      results showed that in human gastric cancer, the expression of GOLPH2 was
      significantly higher and the expression of IL-12A was lower than in normal
      gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were
      negatively correlated. In addition, obvious down-regulation of the Th1 response
      was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells
      over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and
      inhibited the expression of TNF-alpha and IFN-gamma. The results indicated that
      GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric
      cancer, and this might provide a target for the prevention and treatment. 

PMID- 24289574
TI  - Clearance of cervical human papillomavirus infection by topical application of
      curcumin and curcumin containing polyherbal cream: a phase II randomized
      controlled study.
AB  - Curcumin and curcumin containing polyherbal preparations have demonstrated anti
      microbial and anti- viral properties in pre-clinical studies. Till date no
      therapeutic intervention has been proved to be effective and safe in clearing
      established cervical human papillomavirus (HPV) infection. The present study
      evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of
      curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to
      eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA
      test by PCR. HPV positive women without high grade cervical neoplasias (N=287)
      were randomized to four intervention arms to be treated with vaginal Basant
      cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal
      capsules respectively. All subjects were instructed to use one application of the
      assigned formulation daily for 30 consecutive days except during menstruation and
      recalled within seven days of the last application for repeat HPV test, cytology
      and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher
      than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance
      (81.3%) than placebo though the difference was not statistically significant.
      Vaginal irritation and itching, mostly mild to moderate, was significantly higher
      after Basant application. No serious adverse events were noted. 

PMID- 24289575
TI  - The XRCC1 Arg399Gln genetic polymorphism contributes to hepatocellular carcinoma
      susceptibility: an updated meta-analysis.
AB  - The potential correlation of X-ray repair cross-complementing group 1 (XRCC1)
      Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is
      ambiguous. Taking account of inconsistent results of previous meta-analyses and
      new emerging literatures, we conducted a meta-analysis covering 15 case-control
      datasets to evaluate the relationship. Relevant studies from Medline, Embase and
      CNKI were retrieved. A fixed- effect model or a random-effect model, depending on
      between-study heterogeneity, were applied to estimate the association between
      XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds
      ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy
      Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in
      this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was
      significantly associated with HCC susceptibility in a homozygote model as well as
      in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281,
      p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271,
      p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar
      results were also observed on stratification analysis by ethnicity (A/G vs. A/A,
      OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371,
      p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to
      HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was
      found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes
      to HCC susceptibility. Due to the lack of studies in Western countries, further
      large-sample and rigorous studies are needed to validate the findings. 

PMID- 24289576
TI  - Differences in health promoting lifestyle behavior of health management students
      based upon early diagnosis coverage in a cancer course.
AB  - BACKGROUND: This is a descriptive study to determine whether coursework that is
      focused on early diagnosis in cancer makes a difference in self-reported health
      promoting lifestyle behavior of students who study health management. MATERIALS
      AND METHODS: The population of the study consisted of a sample of 104 students
      enrolled in the Department of Health Management at the Faculty of Health in
      Kirikkale University in Turkey. Forty- eight students enrolled in a course called
      "Early Diagnosis of Cancer" and fifty-six did not take this course. Demographic
      information was collected and the "Health Promotion Life-Style Profile (HPLP) "
      was used to collect health promotion data. Frequency and descriptive statistics
      including one-way ANOVA, Mann-Whitney U test, Kruskal Wallis tests were used to
      evaluate data. RESULTS: The HPLP mean score of the students was found to be
      127.5+/-17.45. The highest mean score was observed for self-fulfillment and
      health responsibility, while the lowest was for diet and exercise sub-scales. It
      was found that certain variables were effective in developing health promoting
      lifestyle behaviors such as choosing this job voluntarily, working status of
      father and participation in social activity (p<0.05). In conclusion, it was found
      that the students had moderate levels of health promoting lifestyle behavior and
      they should be supported in terms of diet and exercise.

PMID- 24289577
TI  - Clinicopathological features and prognosis of gastroenteropancreatic
      neuroendocrine tumors: analysis from a single-institution.
AB  - BACKGROUND: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the
      most common type of neuroendocrine neoplasm. We summarized data in our centre to
      investigate the clinicopathological features, diagnostic methods, therapeutic
      approaches and prognosis for this neoplasm to increase knowledge of this disease
      in Asian populations. METHOD: A total of 122 patients treated at Sun Yet-san
      Memorial Hospital of Sun Yat-sen University between January 2000 and December
      2011 were analyzed retrospectively. RESULTS: Pancreas was the most common site of
      involvement (65/122, 53.3%); this disease has no special symptoms; positive rates
      of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%,
      respectively. The positive rate of Syn had statistical difference among the three
      grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3
      tumors, and Chi-square test showed that higher grading was correlated with worse
      prognosis (chi2=32.825, P=0.0001). A total of 32 patients presented with distant
      metastasis, and 8 cases emerged during following up. Cox proportional hazards
      regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis
      (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable
      prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate
      of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. CONCLUSIONS:
      The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the
      last 12 years. All grades of these diseases metastasize readily, and further
      research regarding the treatment of patients after radical surgery is needed to
      prolong disease-free survival.

PMID- 24289578
TI  - Fenugreek induced apoptosis in breast cancer MCF-7 cells mediated independently
      by fas receptor change.
AB  - Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to
      treat disorders like diabetes, high cholesterol, wounds, inflammation,
      gastrointestinal ailments, and it is believed to have anti-tumor properties,
      although the mechanisms for the activity remain to be elucidated. In this study,
      we prepared a methanol extract from Fenugreek whole plants and investigated the
      mechanism involved in its growth-inhibitory effect on MCF- 7 human breast cancer
      cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue
      exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR
      assays inducing activities, in the presence of FME at 65 MUg/mL for 24 and 48
      hours. FME induced apoptosis was mediated by the death receptor pathway as
      demonstrated by the increased level of Fas receptor expression after FME
      treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53,
      FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent
      manner. In summary, these data demonstrate that at least 90% of FME induced
      apoptosis in breast cell is mediated by Fas receptor-independently of either
      FADD, Caspase 8 or 3, as well as p53 interdependently. 

PMID- 24289579
TI  - High mobility group box 1 protein is methylated and transported to cytoplasm in
      clear cell renal cell carcinoma.
AB  - BACKGROUND: The high mobility group box 1 (HMGB1) protein is a widespread nuclear
      protein present in most cell types. It typically locates in the nucleus and
      functions as a nuclear cofactor in transcription regulation. However, HMGB1 can
      also localize in the cytoplasm and be released into extracellular matrix, where
      it plays critical roles in carcinogenesis and inflammation. However, it remains
      elusive whether HMGB1 is relocated to cytoplasm in clear cell renal cell
      carcinoma (ccRCC). METHODS: Nuclear and cytoplasmic proteins were extracted by
      different protocols from 20 ccRCC samples and corresponding adjacent renal
      tissues. Western blotting and immunohistochemistry were used to identify the
      expression of HMGB1 in ccRCC. To elucidate the potential mechanism of HMGB1
      cytoplasmic translocation, HMGB1 proteins were enriched by immunoprecipitation
      and analyzed by mass spectrometry (MS). RESULTS: The HMGB1 protein was
      overexpressed and partially localized in cytoplasm in ccRCC samples (12/20, 60%,
      p<0.05). Immunohistochemistry results indicated that ccRCC of high nuclear grade
      possess more HMGB1 relocation than those with low grade (p<0.05). Methylation of
      HMGB1 at lysine 112 in ccRCC was detected by MS. Bioinformatics analysis showed
      that post-translational modification might affect the binding ability to DNA and
      mediate its translocation. CONCLUSION: Relocation of HMGB1 to cytoplasm was
      confirmed in ccRCC. Methylation of HMGB1 at lysine 112 might the redistribution
      of this cofactor protein.

PMID- 24289581
TI  - Glaucocalyxin A activates FasL and induces apoptosis through activation of the
      JNK pathway in human breast cancer cells.
AB  - THis study was conducted to analyze the molecular mechanisms responsible for anti
      proliferation effects of glaucocalyxin A in cultured MCF-7 and Hs578T breast
      cancer cells. The concentration that reduced cell viability to 50% (IC50) after
      72 h treatment was derived and potential molecular mechanisms of anti
      proliferation using the IC50 were investigated as changes in cell cycle arrest
      and apoptosis. Gene and protein expression changes related to apoptosis were
      investigated by semi-quantitative RT-PCR and western blotting, respectively.
      Involvement of phosphorylated mitogen-activated protein kinases and JNK signaling
      in regulation of these molecules was characterized by western blotting. Cell
      viability decreased in a concentration-dependent manner and the IC50 was
      determined as 1 MUM in MCF-7 and 4 MUM in Hs578T cell. Subsequently, we
      demonstrated that the GLA-induced MCF-7 and Hst578T cell death was due to cell
      cycle arrest at the G2/M transition and was associated with activation of the c
      jun N-terminal kinase (JNK) pathway. We conclude that GLA has the potential to
      inhibit the proliferation of human breast cancer cells through the JNK pathway
      and suggest its application forthe effective therapy for patients with breast
      cancer. 

PMID- 24289580
TI  - Curcumin conjugates induce apoptosis via a mitochondrion dependent pathway in MCF
      7 and MDA-MB-231 cell lines.
AB  - In order to enhance the bioavailability of curcumin its conjugates with piperic
      acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls,
      the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of
      synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. IC50
      values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were
      found to be comparable with that of curcumin. Both conjugates induced chromatin
      condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7
      cells induced apoptosis initiating loss of mitochondrial membrane potential
      (Deltapsim) followed by inhibition of translocation of transcription factor NF-kB
      and release of Cytochrome-C. Reactive oxygen species (ROS) production was
      evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/ Bclxl
      was observed, suggesting permeablization of mitochondrial membrane leading to the
      release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a
      hallmark for apoptosis was monitored by TUNEL as well as agrose gel
      electrophoresis. Thus, it was proven that conjugation does not affect the
      therapeutic potential of parent molecule in vitro, while these could work in vivo
      as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these
      molecules under in vivo conditions is a further scope of this study. 

PMID- 24289582
TI  - Disease free survival among molecular subtypes of early stage breast cancer
      between 2001 and 2010 in Iran.
AB  - BACKGROUND: Breast cancer is the most common cancer among women. Molecular
      subtypes are important in determining prognosis. This study evaluated five-year
      disease-free survival among four molecular subtypes in patients with early stages
      of breast cancer. MATERIALS AND METHODS: In this retrospective descriptive
      analytical study, information on patients with breast cancer between 2001-2010
      was evaluated. Five hundred ninety two patients in the early stages of breast
      cancer (stages 1 and 2) were selected to undergo anthracycline-based
      chemotherapy. Relapse, death or absence (censor) were considered as the end of
      the study. Patients based on ER, PR and HER-2 expression were divided into four
      subtypes (luminal A, luminal B, HER-2 enriched and triple negative). Information
      based upon questionnaire was analysed. To show the patients survival rate, life
      table and Kaplan-Meyer methods were used, and for comparing mean survival among
      different groups, the Log-Rank test was utilized. RESULTS: Mean age at diagnosis
      was 47.9+/-9.6. Out of the 592 patients, 586 were female (99%) and 6 were male
      (1%). Considering breast cancer molecular subtypes, 361 patients were in the
      luminal A group (61%), 49 patients in the luminal B group (8.3%), 48 patients in
      the HER-2 enriched group (8.1%) and 134 in the triple negative group (22.6%).
      Mean disease-free survival was 53.7 months overall, 55.4 months for the luminal A
      group, 48.3 months for the luminal B group, 43 months for the HER-2enriched group
      and 54.6 months for the triple negatives. Disease free survival differed
      significantly among the molecular subtypes (p value=0.0001). CONCLUSIONS: The
      best disease-free survival rate was among the luminal A subgroup and the worst
      disease-free survival rate was among the HER-2 enriched subgroup. Disease free
      survival rate in the HER-2 positive groups (luminal B and HER-2 enriched) was
      worse than the HER-2 negative groups (luminal A and triple negative).

PMID- 24289583
TI  - Oncologist perspectives on breast cancer screening in India- results from a
      qualitative study in Andhra Pradesh.
AB  - BACKGROUND: It is important to understand the perceptions of oncologists to
      understand the comprehensive picture of clinical presentation of breast cancer.
      In the absence of clear evidence, clinical practice involving patients of breast
      cancer in India should provide insights into stages of breast cancer with which
      women present to their clinics and mode of screening of breast cancer prevalent
      in Andhra Pradesh. MATERIALS AND METHODS: A qualitative study was conducted to
      understand the perceptions of oncologists regarding clinical presentation of
      breast cancer, stages at which women present to clinics, and mode of screening of
      breast cancer prevalent in Andhra Pradesh. In-depth interviews (IDI) were
      conducted with ten practising oncologists from various public and private cancer
      hospitals in Hyderabad city to understand their perspectives on breast cancer and
      screening. The data were triangulated to draw inferences suitable for the current
      public Health scenario. RESULTS: Late presentation was indicated as the most
      important cause of decreased survival among women. Most women present at Stage 3
      and 4 when there is no opportunity for surgical intervention. The results
      indicate that there is a huge gap in awareness about breast cancer, especially in
      rural areas and among poor socioeconomic groups. Even despite knowledge, most
      women delay in reporting due to reasons like fear, embarrassment, cost,
      ignorance, negligence, and easy going attitude. CONCLUSIONS: It is important to
      improve awareness about breast cancer and screening methods for promoting early
      screening. The study inferred that it would be beneficial to establish cancer
      registries in rural areas. Also, the policymakers need to make key decisions
      which among three methods (breast self examination (BSE), clinical breast
      examination and mammography) can best be used as a screening tool and how to
      successfully implement population wide screening program to prevent mortality and
      morbidity from breast cancer in India.

PMID- 24289584
TI  - Multiple cytotoxic factors involved in IL-21 enhanced antitumor function of CIK
      cells signaled through STAT-3 and STAT5b pathways.
AB  - BACKGROUND/OBJECTIVES: Maintenance of cellular function in culture is vital for
      transfer and development following adoptive immunotherapy. Dual properties of IL
      21 in activating T cells and reducing activation induced cell death led us to
      explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic
      potential of CIK cells. METHOD: CIK cells cultured from PBMCs of healthy subjects
      were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells
      were measured. To elucidate the mechanism of action of IL-21, mRNA expression of
      cytotoxic factors was assessed by RT-PCR and protein expression of significantly
      important cytotoxic factors and cytokine secretion were determined through flow
      cytometry and ELISA. Western blotting was performed to check the involvement of
      the JAK/STAT pathway following stimulation. RESULTS: We found that IL-21 did not
      enhance in vitro proliferation of CIK cells, but did increase the number of cells
      expressing the CD3+/ CD56+ phenotype. Cytotoxic potential was increased with
      corresponding increase in perforin (0.9831+/-0.1265 to 0.7592+/-0.1457), granzyme
      B (0.4084+/-0.1589 to 0.7319+/-0.1639) and FasL (0.4015+/-0.2842 to 0.7381+/
      0.2568). Interferon gamma and TNF-alpha were noted to increase (25.8+/-6.1 ng/L
      to 56.0+/-2.3 ng/L; and 5.64+/-0.61 MUg/L to 15.14+/-0.93 MUg/L, respectively)
      while no significant differences were observed in the expression of granzyme A,
      TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through
      the STAT-3 and STAT- 5b signaling pathway in the CIK cell pool. CONCLUSION: IL-21
      enhances cytotoxic potential of CIK cells through increasing expression of
      perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the
      activation of STAT-3 and STAT-5b proteins.

PMID- 24289585
TI  - Association of a VDR gene polymorphism with risk of colorectal cancer in Kashmir.
AB  - Roles of the vitamin D receptor in etiology of cancers, including colorectal
      cancer, have been repeatedly stressed in different parts of the world. A case
      control study aimed to evaluate the relationship between the two was therefore
      initiated in Kashmir, known both for its increasing incidence of gastrointestinal
      cancers and deficiency of micro-nutrients especially vitamin D. The study
      included a total of 617 subjects (312 colorectal cancer cases and 305 controls),
      with sampling carried out over a period of 5 years. DNA samples from the blood of
      the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a
      1.3 fold increased risk among individuals homozygous for f variants as compared
      to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our
      study also showed statistically significant results when dwelling and tumor
      location characteristics were stratified with Fok I polymorphism, all of which
      suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

PMID- 24289586
TI  - Role of DNA repair-related gene polymorphisms in susceptibility to risk of
      prostate cancer.
AB  - AIM: We assessed the association between genetic variants of XPG, XPA, XPD, CSB,
      XPC and CCNH in the nucleotide excision repair (NER) pathway and risk of prostate
      cancer. METHODS: We genotyped the XPG, XPA, XPD, CSB, XPC and CCNH polymorphisms
      by a 384-well plate format on the MassARRAY(r) platform. Multivariate logistical
      regression analysis was used to assess the associations between the six gene
      polymorphisms and risk of prostate cancer. RESULTS: Individuals carrying the XPG
      rs229614 TT (OR=2.01, 95%CI=1.35-3.27) genotype and T allele (OR=1.73, 95%CI=1.37
      2.57) were moderately significantly associated with a higher risk of prostate
      cancer. Subjects with XPD rs13181 G allele had a marginally increased risk of
      prostate cancer, with adjusted OR(95%CI) of 1.53 (1.04-2.37). Moreover,
      individuals carrying with CSB rs2228526 GG genotype (OR=2.05, 95% CI=1.23-3.52)
      and G allele (OR=1.56, 95%CI=1.17-2.05) were associated with a higher increased
      risk of prostate cancer. The combination genotype of XPG rs2296147 T and CSB
      rs2228526 G allele had accumulative effect on the risk of this cancer, with an OR
      (95% CI) of 2.23(1.37-3.59). CONCLUSIONS: Our study indicates that XPG rs2296147
      and CSB rs2228526 polymorphisms are significantly associated with increased risk
      of prostate cancer, and that combination of XPG rs2296147 T allele and CSB
      rs2228526 G allele is strongly associated with an increased risk.

PMID- 24289587
TI  - HPV genotyping linear assay test comparison in cervical cancer patients:
      implications for HPV prevalence and molecular epidemiology in a limited-resource
      area in Bandung, Indonesia.
AB  - BACKGROUND: Persistent infection with high risk human papillomavirus (hrHPV) is
      strongly associated with cervical cancer. Normal cervical cells may also harbor
      hrHPV, and detection of early hrHPV infection may minimize risk of cervical
      cancer development. This study aimed to compare two commercial HPV genotyping
      assays that may affordable for early screening in a limited-resource setting in
      Bandung, Indonesia. MATERIALS AND METHODS: DNA from cervical biopsies with
      histologically confirmed as squamous cell cervical cacinoma were HPV genotyped by
      Linear Assay 1 (Roche Diagnostics, Mannheim, Germany) or Linear Assay 2 (Digene
      HPV Genotyping RH Test, Qiagen Gaithersburg, MD). In a subset of samples of each
      group, HPV genotype results were then compared. RESULTS: Of 28 samples genotyped
      by linear assay 1, 22 (78.6%) demonstrated multiple infections with HPV-16 and
      other hrHPV types 18, 45 and/or 52. In another set of 38 samples genotyped by
      linear assay 2, 28 (68.4%) were mostly single infections by hrHPV type 16 or 18.
      Interestingly, 4 samples that had been tested by both kits showed discordant
      results. CONCLUSIONS: In a limited-resource area such as in Indonesia, country
      with a high prevalence of HPV infection a reliable cervical screening test in
      general population for early hrHPV detection is needed. Geographical variation in
      HPV genotyping result might have impacts for HPV prevalence and molecular
      epidemiology as the distribution in HPV genotypes should give clear information
      to assess the impact of HPV prophylactic vaccines.

PMID- 24289588
TI  - Blocking Bcl-2 leads to autophagy activation and cell death of the HEPG2 liver
      cancer cell line.
AB  - BACKGROUND: Apoptosis may be induced after Bcl-2 expression is inhibited in
      proliferative cancer cells. This study focused on the effect of autophagy
      activation by ABT737 on anti-tumor effects of epirubicin. METHODS: Cytotoxic
      effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay
      and cell apoptosis through flow cytometry. Mitochondrial membrane potential was
      measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used
      to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1,
      apoptotic or autophagy related proteins, was detected by Western blotting.
      RESULTS: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose
      and time-dependent manner. Both ABT737 and epirubicin alone could induce cell
      apoptosis with a reduction in mitochondrial membrane potential as well as
      increased apoptotic protein expression. Further increase of apoptosis was
      detected when HepG2 cells were co- treated with ABT373 and epirubicin.
      Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate
      cell autophagy with elevated autophagosome formation, increased expression of
      autophagy related proteins and LC3 fluorescent puncta. CONCLUSIONS: ABT737
      influences cancer cells through both apoptotic and autophagic mechanisms, and
      ABT737 may enhance the effects of epirubicin on HepG2 cells by activating
      autophagy and inducing apoptosis.

PMID- 24289589
TI  - Sulforaphane inhibits growth of human breast cancer cells and augments the
      therapeutic index of the chemotherapeutic drug, gemcitabine.
AB  - Phytochemicals are among the natural chemopreventive agents with most potential
      for delaying, blocking or reversing the initiation and promotional events of
      carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer
      related death. One such promising chemopreventive agent which has attracted
      considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti
      diabetic, and anti-microbial properties. The present study was undertaken to
      assess effect of SFN alone and in combination with a chemotherapeutic agent,
      gemcitabine, on the proliferative potential of MCF-7 cells by cell viability
      assay and authenticated the results by nuclear morphological examination. Further
      we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these
      cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose-
      and time-dependent manner via an apoptotic mode of cell death. In addition, a
      combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth
      inhibition in a synergistic manner with a combination index (CI) <1. Notably, SFN
      was found to significantly downregulate the expression of Bcl-2, an anti
      apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent
      manner. These results indicate that SFN induces apoptosis and anti-inflammatory
      effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The
      combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and
      minimize the toxicity to normal cells. Taken together, SFN may be a potent anti
      cancer agent for breast cancer treatment. 

PMID- 24289590
TI  - Genotype distribution and behavioral risk factor analysis of human papillomavirus
      infection in Uyghur women.
AB  - We investigated the distribution of HPV genotypes in Uyghur women in Xinjiang
      region of China, and behavioral factors which could predispose them to HPV
      infection. In this cross-sectional study, women aged 15-59 years were recruited
      by cluster sampling method in Yutian region in 2009. Liquid-based cytology
      samples were analyzed centrally for HPV genotype with a linear array detector.
      Univariate and multivariate logistic regression analyses were performed to
      identify behavioral risk factors for HPV infection. A total of 883 Uyghur women
      were recruited successfully. The prevalence of high-risk HPV and low-risk HPV
      were 7.25% and 1.58%, respectively; the most common HPVs were HPV16, 51, 31, 39
      and 58. We found that age of first sexual intercourse was a strong predictor for
      HPV infection (odds ratio of 4.01 for <= 15 years versus >=25). Having sexual
      partners >= 3 was the second predictor (OR 3.69, 95% CI 2.24-7.16). Cleaning the
      vagina after sex showed an increased risk of HPV infection (OR 2.72; 95% CI 1.98
      5.13); Using the condom showed protective factors for HPV infection (OR 0.36;
      95%CI0.12-0.53). HPV16, 51, 31, 39 and 58 were the priority types; the age of
      first sexual intercourse was identified as a major risk factor for HPV infection.
      Other notable risks were number of sexual partners and cleaning the vagina after
      sex. Changing these behavioral risk factors could help to reduce the occurrence
      of cervical cancer in this population. 

PMID- 24289591
TI  - Study protocol for the most effective recall method in a cervical cancer
      screening program in Klang, Malaysia.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among Malaysian
      women with an ASR of 17.9 and a mortality rate of 5.6 per 100,000 population in
      2008 (GLOBOCAN, 2008). The 5 year prevalence was estimated to be 14.5 per 100,000
      population. As the second most common cancer affecting productive females,
      cervical cancer imposes an impact to the socioeconomic aspect of the country.
      However, the poor uptake of cervical cancer screening is a major problem in
      detecting early pre-cancerous lesions and thus, delay in initiating treatment for
      cervical cancer. Realizing the urgency to increase the uptake of PAP smear,
      besides enhancing the promotion of PAP smear screening for women above 35 years
      old, the call-recall system for pap smear screening had been piloted in one of
      the suburban districts which aimed to improve regular participation of women for
      cervical and breast cancer screening. This is of public health importance as
      identifying the best feasible option to increase patient's respond to participate
      in the screening program effectively in our setting will be helpful in
      implementing an organized regular population based screening program tailored to
      our setting. The pilot program of cervical cancer screening in Klang was an
      opportunity to assess different options in recalling patients for a repeat pap
      smear to increase their participation and adherence to the program. METHODS AND
      RESULTS: This was a population based randomized control trial. Women aged 20-65
      years in the population that matched the inclusion and exclusion criteria were re
      called for a repeat smear. There are four different intervention groups; letter,
      registered letters, short messages services (SMS) and phone calls where 250
      subjects were recruited into each group. Samples were generated randomly from the
      same population in Klang into four different groups. The first group received a
      recall letter for a repeat smear similar to the one that has been given during
      the first invitation. The intervention groups were either be given a registered
      letter, an SMS or a phone call to re-call them. The socio-demographic data of the
      patients who came for uptake were collected for further analysis. All the groups
      were followed up after 8 weeks to assess their compliance to the recall.
      CONCLUSIONS: The study will provide recommendations about the most effective
      methods for recall in a population based pap smear screening program on two
      outcomes: i) patients response; ii) uptake for repeat pap smear.

PMID- 24289592
TI  - Lack of association of three common polymorphisms in toll-like receptors (TLRs),
      TLR2+597T>C, +1350C>T and Arg753Gln with cancer risk: a meta-analysis.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) occurring in Toll-like
      receptors (TLRs) may contribute to cancer risk. Many polymorphisms of TLR2 have
      been studied for associations, but the findings are conflicting.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 14 studies to
      confirm the association between TLR2+597T>C (rs3804099), +1350C>T (rs3804100) and
      Arg753Gln (rs5743708) polymorphisms and cancer risk. Odds ratio (OR) and 95%
      confidence intervals (95% CI) were used to assess the strength of associations.
      There was no significant association between TLR2+597T>C and cancer risk in the
      codominant models (CC vs. TT: OR = 1.01, 95%CI = 0.86-1.17, Pheterogeneity =
      0.148; CT vs. TT: OR = 0.92, 95%CI = 0.69-1.23, Pheterogeneity < 0.001), the
      recessive model (CC vs. CT+TT: OR = 0.86, 95%CI = 0.67-1.10, Pheterogeneity =
      0.007) , the dominant model (CC+CT vs. TT: OR = 0.93, 95%CI = 0.76-1.15,
      Pheterogeneity = 0.001) and the allele model (C vs. T: OR = 0.93, 95%CI = 0.81
      1.08, Pheterogeneity = 0.019). Similarly, no significant associations between
      TLR2+1350C>T, Arg753Gln polymorphisms and cancer risk were found. However, in the
      sub-group analysis of ethnicities, the trend of pooled ORs in Asians was opposite
      to Caucasians. CONCLUSIONS: The present meta-analysis suggests that TLR2+597T>C
      (rs3804099), +1350C>T (rs3804100) and Arg753Gln (rs5743708) polymorphisms are not
      associated with cancer risk.

PMID- 24289593
TI  - Breast cancer risk and early diagnosis applications in Turkish women aged 50 and
      over.
AB  - BACKGROUND: The aim of the study was to determine breast cancer risk and early
      diagnosis applications in women aged >=50. MATERIALS AND METHODS: This cross
      sectional, descriptive field study focused on a population of 4,815 in
      Mansurog?lu with a 55.1% participation rate in screening. In the study, body mass
      index (BMI) was also evaluated in the calculation of breast cancer risk by the
      Breast Cancer Risk Assessment Tool (BCRA) (also called the "Gail Risk Assessment
      Tool") . The interviewers had a three-hour training provided by the researchers,
      during which interactive training methods were used and applications were
      supported with role-plays. RESULTS: The mean age of the women participating in
      the study was 60.1+/-8.80. Of these women, 57.3% were in the 50-59 age group,
      71.7% were married, 57.3% were primary school graduates and 61.7% were
      housewives. Breast-cancer development rate was 7.4% in the women participating in
      the study. When they were evaluated according to their relationship with those
      with breast cancer, it was determined that 73.0% of them had first- degree
      relatives with breast cancer. According to the assessment based on the Gail
      method, the women's breast cancer development risk within the next 5 years was
      17.6%, whereas their calculated lifetime risk was found to be as low as 0.2%.
      Statistically significant differences (P=0.000) were determined between
      performing BSE - CBE and socio-demographic factors. CONCLUSIONS: It was
      determined that 17.6% of the participants had breast cancer risk. There was no
      statistically significant difference between the women with and without breast
      cancer risk in terms of early diagnosis practices, which can be regarded as a
      remarkable finding. It was planned to provide training about the early diagnosis
      and treatment of breast cancer for people with high-risk scores, and to conduct
      population-based breast cancer screening programs.

PMID- 24289594
TI  - Overexpression of Semaphorin4D indicates poor prognosis and prompts monocyte
      differentiation toward M2 macrophages in epithelial ovarian cancer.
AB  - Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be
      closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs).
      However, the function and expression of SEMA4D in the EOC microenvironment has
      yet to be clarified in detail. In this study, we confirmed that overexpression of
      SEMA4D in primary tumors and ascites was related to low differentiation, platinum
      resistance and a refractory status (P<0.05), while high M2 macrophage count and
      percentage were evident in EOC patients with advanced FIGO stage and platinum
      resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent
      assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The
      data showed correlations of SEMA4D expression and M2 macrophage counts in primary
      tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05).
      In the Cox proportional hazard mode, SEMA4D expression was an independent
      indicator of overall survival (OS) and progression-free survival (PFS) for EOC
      patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines
      (SKOV3, A2780, and SW626) and their supernatants were found than that in a human
      primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT
      PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood
      monocytes (MOs) tended towards the M2-polarized macrophage phenotype (CD163high)
      in vitro after human recombined soluble SEMA4D protein stimulation. These
      findings suggest that SEMA4D might possibly serve as a reliable tool for early
      and accurate prediction of EOC poor prognosis and could playan important role in
      promoting tumor dissemination and metastasis in the EOC microenvironment. Thus
      SEMA4D and its role in macrophage polarization in EOC warrants further study. 

PMID- 24289595
TI  - Cohort analysis of incidence/mortality of liver cancer in Japan through logistic
      curve fitting.
AB  - Incidence/mortality of liver cancer follow logistic curves because there is a
      limit reflecting the prevalence of hepatitis virus carriers in the cohort. The
      author fitted logistic curves to incidence/mortality data covering the nine five
      year cohorts born in 1911-1955 of both sexes. Goodness-of-fit of logistic curves
      was sufficiently precise to be used for future predictions. Younger cohorts born
      in 1936 or later were predicted to show constant decline in incidence/mortality
      in the future. The male cohort born in 1931-35 showed an elevated
      incidence/mortality of liver cancer early in their lives supporting the previous
      claim that this particular cohort had suffered massive HCV infection due to
      nation-wide drug abuse in the 1950s. Declining case-fatality observed in younger
      cohorts suggested improved treatment of liver cancer. This study demonstrated
      that incidence/mortality of liver cancer follow logistic curves and fitted
      logistic formulae can be used for future prediction. Given the predicted decline
      of incidence/mortality in younger cohorts, liver cancer is likely to be lost to
      history in the not-so-distant future. 

PMID- 24289596
TI  - Dihydroartemisinine enhances dictamnine-induced apoptosis via a caspase dependent
      pathway in human lung adenocarcinoma A549 cells.
AB  - Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon,
      and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer
      activity on various tumour cell lines. This report explores the molecular
      mechanisms by which Dic treatment and combination treatment with DHA and Dic
      cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced
      concentration- and time-dependent cell death. FCM analysis showed that Dic
      induced S phase cell cycle arrest at low concentration and cell apoptosis at high
      concentration in which loss of mitochondrial membrane potential (Deltapsimm) was
      not involved. In addition, inhibition of caspase-3 using the specific inhibitor,
      z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced
      caspase-3-independent apoptosis. Combination treatment with DHA and Dic
      dramatically increased the apoptotic cell death compared to Dic alone.
      Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic
      co-induced apoptosis, implying that caspase-3 plays an important role in Dic and
      DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase
      cell cycle arrest at low concentration and cell apoptosis at high concentration
      in which mitochondria and caspase were not involved and DHA enhanced Dic induced
      A549 cell apoptosis via a caspase-dependent pathway. 

PMID- 24289597
TI  - Is the phone call the most effective method for recall in cervical cancer
      screening?--results from a randomised control trial.
AB  - OBJECTIVE: To compare the effectiveness of different methods of recall for repeat
      Pap smear among women who had normal smears in the previous screening. DESIGN:
      Prospective randomized controlled study. SETTING: All community clinics in Klang
      under the Ministry of Health Malaysia. PARTICIPANTS: Women of Klang who attended
      cervical screening and had a normal Pap smear in the previous year, and were due
      for a repeat smear were recruited and randomly assigned to four different methods
      of recall for repeat smear. INTERVENTION: The recall methods given to the women
      to remind them for a repeat smear were either by postal letter, registered
      letter, short message by phone (SMS) or phone call. MAIN OUTCOME MEASURES: Number
      and percentage of women who responded to the recall within 8 weeks after they had
      received the recall, irrespective whether they had Pap test conducted. Also the
      numbers of women in each recall method that came for repeat Pap smear. RESULTS:
      The rates of recall messages reaching the women when using letter, registered
      letter, SMS and phone calls were 79%, 87%, 66% and 68%, respectively. However,
      the positive responses to recall by letter, registered letter, phone messages and
      telephone call were 23.9%, 23.0%, 32.9% and 50.9%, respectively (p<0.05).
      Furthermore, more women who received recall by phone call had been screened
      (p<0.05) compared to those who received recall by postal letter (OR=2.38, CI=1.56
      3.62). CONCLUSION: Both the usual way of sending letters and registered letters
      had higher chances of reaching patients compared to using phone either for
      sending messages or calling. The response to the recall method and uptake of
      repeat smear, however, were highest via phone call, indicating the importance of
      direct communication.

PMID- 24289598
TI  - Effects of garlic oil on pancreatic cancer cells.
AB  - BACKGROUND: To investigate the preventive and therapeutic potential of garlic oil
      on human pancreatic carcinoma cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects
      of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and
      PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry
      (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium
      iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were
      observed under transmission electron microscopy (TEM) after treatment with garlic
      oil at low inhibitory concentrations (2.5 MUM and 10 MUM) for 24 hours. RESULTS:
      Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited
      in the first 24 hours with the MTT assay. The inhibition effect was more
      significant after 48 hours. When cells were exposed to garlic oil at higher
      concentrations, an early change of the apoptotic tendency was detected by FCM and
      TEM. CONCLUSION: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1,
      and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell
      cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by
      garlic oil in a dose and time dependent manner in vitro.

PMID- 24289599
TI  - Cyclamen exerts cytotoxicity in solid tumor cell lines: a step toward new
      anticancer agents?
AB  - Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer
      properties and whether cyclamen extract induces any cytotoxicity in solid cancer
      cell lines have not been thoroughly investigated previously. Therefore we
      examined cytotoxic effects on cervical cancer, HeLa, and non small cell lung
      cancer cell, H1299, lines. Cyclamen extract induced cellular death of both HeLa
      and H1299 cells in a dose dependent manner. We also analyzed the capacity of
      cyclamen extract to induce apoptosis by the TUNEL method. Here, we for the first
      time report that the extract of Cyclamen coum, an endemic plant for Turkey, can
      induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply
      that cyclamen extract can be further analyzed to potentially find novel
      anticancer compounds. 

PMID- 24289600
TI  - MicroRNA-101 inhibits cell proliferation, invasion, and promotes apoptosis by
      regulating cyclooxygenase-2 in Hela cervical carcinoma cells.
AB  - AIM: Although aberrant miRNA expression has been documented, altered miR-101
      expression in cervical cancer and its carcinogenic effects and mechanisms remain
      unexplored. The aim of our study was to investigate the role of miR-101
      alteration in cervical carcinogenesis. METHODS: Expression of miR-101 was
      examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela
      cells. After modulating miR-101 expression using miR-101 mimics, cell growth,
      apoptosis and proliferation, and migration were tested separately by MTT or flow
      cytometry and cell wound healing assay and protein expression was detected by qRT
      PCR. The expression of COX-2 in Hela cell was also examined by
      immunohistochemical staining and the correlation with miR-101 expression was
      analysed. RESULTS: The miR-101 demonstrated significantly low expression in Hela
      cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR
      101 expression remarkably influenced cell proliferation, cycling and apoptosis:
      1) The expression of microRNA-101 tended to increase after transfection; 2)
      Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate
      being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P <0.05);
      3) The miR-101 negatively regulates cell migration and invasion, scratch results
      being lower (42.7um+/-2um) than that observed pre-transfection (181.4 um+/-2 um);
      4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX
      2 protein, which was negatively correlated with miR-101 expression. CONCLUSIONS:
      Overexpression of miR-101 has obvious inhibitory effects on cell proliferation,
      migration and invasion. Thus reduced miR-101 expression could participate in the
      development of cervical cancer at least partly through loss of inhibition of
      target gene COX-2, which probably occurs in a relative late phase of
      carcinogenesis. Our data suggest an important role of miR-101 in the molecular
      etiology of cancer and indicate potential application of miR-101 in cancer
      therapy.

PMID- 24289601
TI  - Mexican breast cancer research output, 2003-2012.
AB  - The objetive of this study was to explore a bibliometric approach to
      quantitatively assess current research trends with regard to breast cancer in
      Mexico. Articles were analyzed by scientific output and research performances of
      individuals, institutes, and collaborative countries with Mexico. Data were
      retrieved from the Web of Science database from 2003 to 2012; this was searched
      using different terms related to breast cancer, including "breast cancer",
      "mammary ductal carcinoma" and "breast tumour". Data were then extracted from
      each file, transferred to Excel charts and visualised as diagrams. A total of 256
      articles were retrieved. The institutions with the majority of publications were
      the National Autonomous University of Mexico (22.3%), the National Institute of
      Cancerology (21.9%), and Social Security Mexican Institute (20.3%); clinical
      observation studies were the dominant investigation type (64%), and the main
      types of research were metabolics (24.2%) and pathology (21.5%). This article
      demonstrates the usefulness of bibliometrics to address key evaluation questions
      and to establish priorities, define future areas of research, and develop breast
      cancer control strategies in Mexico. 

PMID- 24289602
TI  - Roles of mTOR and p-mTOR in gastrointestinal stromal tumors.
AB  - OBJECTIVE: This study aimed to examine the relationship between expression of
      mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in
      the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and
      relatiuonships with clinical factors. METHODS: Immunohistochemistry was used to
      detect the expression of the associated proteins mTOR, p-mTOR, and
      phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40
      cases of gastrointestinal stromal tumors, with division into a very low and low
      risk group as well as a moderate and high risk group. RESULTS: The positive rate
      of mTOR and p-mTOR was significantly increased in the moderate and high risk
      group compared with the very low and low risk group. The difference was
      statistically significant (P<0.05). When grouped according to size, the positive
      mTOR expression rate exhibited a statistical difference (P<0.05), which was
      significantly increased in the group of tumors larger than 5 cm. The difference
      in the positive mTOR and p-mTOR expression rate exhibit no statistical
      significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05).
      CONCLUSION: The different expressions of mTOR and p-mTOR in the signal
      transduction pathway of gastrointestinal stromal tumor in the different degree-of
      risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway
      serve an important function in the occurrence and development of gastrointestinal
      stromal tumors.

PMID- 24289603
TI  - Investigation of ICAM-1 and beta3 integrin gene variations in patients with brain
      tumors.
AB  - BACKGROUND: Primary brain tumors constitute a small percent of all malignant
      cancers, but their etiology remains poorly understood. beta3 integrin (ITGB3) has
      been recognized to play influential roles in angiogenesis, tumor growth and
      metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein
      important for tumor invasion and angiogenesis. The aim of this study was to
      investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be
      associated with brain cancer development and progression in a Turkish population.
      Our study is the first to our knowledge to investigate the relationship between
      brain tumor risk and ICAM-1 and beta3 integrin gene polymorphisms. MATERIALS AND
      METHODS: The study covered 92 patients with primary brain tumors and 92 age
      matched healthy control subjects. Evaluation of beta3 integrin (Leu33Pro
      (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms
      was performed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). RESULTS: According to results of our research, the A
      allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for
      primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele
      of ICAM-1 R241G was statistically significant in patients with brain tumors
      classified as glioma (p<0.001). When allele and genotype distributions of ICAM- 1
      K469E, ICAM-1 R241G and beta3 integrin Leu33Pro gene polymorphisms were evaluated
      with age, sex, and smoking, there were no statistically significant differences.
      Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918)
      and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients
      as compared with controls (p=0.001; p=0.036 respectively). CONCLUSIONS: This
      study provides the first evidence that ICAM-1 R241G SNP significantly contributes
      to the risk of primary brain tumors in a Turkish population. In addition, our
      results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective
      effects against the development of brain cancer.

PMID- 24289604
TI  - Endometrial Intraepithelial Neoplasia (EIN) in endometrial biopsy specimens
      categorized by the 1994 World Health Organization classification for endometrial
      hyperplasia.
AB  - Our study is to determine the presence of endometrial intraepithelial neoplasia
      (EIN) in endometrial biopsy specimens classified by the 1994 World Health
      Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy
      specimens that were stained with hematoxylin and eosin (HE) were examined and
      categorized by the WHO 1994 criteria and for the presence of EIN as defined by
      the International Endometrial Collaborative Group. beta-catenin expression was
      examined by immunohistochemistry. A total of 474 cases of HE stained endometrial
      biopsy tissues were reviewed. There were 379 cases of simple endometrial
      hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex
      endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia.
      Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were
      classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple
      endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6
      (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical
      endometrial hyperplasia. EIN was associated with a higher rate of beta-catenin
      positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%,
      respectively, P < 0.001), but a lower rate than endometrial adenocarcinoma (72%
      vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, high beta
      catenin expression was noted in the cell membranes, whereas in EIN and
      endometrial adenocarcinoma high expression was noted in the cytoplasm. In
      conclusion, EIN is more accurate than the WHO classification for the diagnosis of
      precancerous lesions of the endometrium. 

PMID- 24289605
TI  - No relationship between the amount of DNA damage and the level of hMLH1 and
      RASSF1A gene expression in bladder cancer cells treated with cisplatin and
      gemcitabine.
AB  - Tumor response to antineoplastic drugs is not always predictable. This is also
      true for bladder carcinoma, a highly recurrent neoplasia. Currently, the
      combination of cisplatin and gemcitabine is well accepted as a standard protocol
      for treating bladder carcinoma. However, in some cases, this treatment protocol
      causes harmful side effects. Therefore, we investigated the roles of the genes
      TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the
      mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine
      treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type
      TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated
      whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53
      status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A
      and hMLH1 expression in the two cell lines. Increased DNA damage was observed in
      both cell lines after treatment with cisplatin or gemcitabine and with the two
      drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A
      expression and hypermethylation of its promoter were observed before and after
      treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated
      to methylation status, was observed in RT4 cells after treatment with cisplatin
      or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells,
      hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the
      three treatment protocols were genotoxic, independent of TP53 status. However,
      cisplatin was the most effective, causing the highest level of DNA damage in both
      wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in
      both cell lines. Furthermore, no relationship was observed between the amount of
      DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other
      alternative pathways might be involved in cisplatin and gemcitabine genotoxicity
      in these two bladder cancer cell lines. 

PMID- 24289606
TI  - Clinical features and survival analysis of very young (age<35) breast cancer
      patients.
AB  - OBJECTIVES: To compare the clinicalpathological features and prognosis between
      premenopausal breast cancer patients aged of <35 and >=35 years old. METHODS: The
      clinical data and survival status of 1498 cases premenopausal operable breast
      cancer treated in our hospital from 2002.1 to 2004. 12 were collected, 118 cases
      were aged <35. They were divided into 4 groups: Luminal A, Luminal B, HER2
      positive, Triple-negative. The disease free survival (DFS) and overall survival
      (OS) were identified. RESULTS: The 5-year DFS and OS rates were significantly
      lower in age<35 than in age>=35 patients. In the Luminal B, HER2-positive, Triple
      negative group, the 5-year recurrence risk was higher in age<35 than in age>=35
      patients, and age<35 patients' 5-year death risk was higher only in Luminal B,
      Triple-negative group. Regardless of whether lymph node involved, age<35 patients
      had a bad prognosis in both DFS and OS. CONCLUSIONS: Compared with premenopausal
      age >=35 breast cancer, age<35 patients had a worse outcome.

PMID- 24289607
TI  - Risk factors for cholangiocarcinoma in the lower part of Northeast Thailand: a
      hospital-based case-control study.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) is the most common cancer in Northeast
      Thailand. It is also a crucial health problem for Thai people. Various risk
      factors for CCA have been identified in the upper part of Northeast Thailand, but
      no similar studies of risk factors have been conducted in the lower parts of the
      region. This study aimed to investigate factors associated with CCA in the
      resident population. MATERIALS AND METHODS: A hospital-based case-control study
      was conducted during 2009-2012 with the recruitment of 123 CCA cases and 123 non
      CCA patient controls, matched for sex, age and residential area. Information was
      collected by interview with a structured questionnaire. Blood samples were
      collected for assays of anti-OV antibodies. Associations between various personal
      factors, dietary habits, family history, the presence of anti-OV antibodies and
      CCA were analyzed using multiple conditional logistic regression. RESULTS:
      Patients who consumed raw meat (beef, pork) and alcoholic beverages >=3 times per
      week had a higher risk of CCA than non-consumers (ORadj=4.33; 95%CI=1.14-16.35
      and ORadj=2.13; 95%CI=1.00-4.55, respectively). Patients who had a family history
      of cancer had a higher risk than those who did not (ORadj=4.34; 95%CI=1.80
      10.43). Also, patients who had anti-OV antibodies (AU>23.337) had a higher risk
      than those whose anti-OV antibodies were below the cut-off (AU<=23.34)
      (ORadj=3.09; 95%CI=1.04-9.16). CONCLUSIONS: As is the case in the upper part of
      Northeast Thailand, OV infection is a crucial risk factor for CCA in people who
      live in lower part of the region. Similarly, a family history of cancer and the
      consumption of alcohol are risk factors for CCA.

PMID- 24289608
TI  - Association between genetic polymorphism of xrcc1 gene and risk of Glioma in ?
      Chinese population.
AB  - BACKGROUND: Gliomas are the most common type of primary brain tumor in adults,
      and the X-ray repair complementing group 1 gene (XRCC1) is an important candidate
      gene influencing its risk. The objective of this study was to detect the
      influence of XRCC1 genetic polymorphisms on glioma risk. MATERIALS AND METHODS: A
      total of 629 glioma patients and 641 cancer-free subjects were enrolled in this
      case-control study. The genotypes of the c.1471G>A genetic polymorphism were
      determined by created restriction site-polymerase chain reaction (CRS-PCR) and
      DNA sequencing methods. The influence of the XRCC1 genetic polymorphism on glioma
      risk was evaluated by association analysis. RESULTS: Our data indicated that the
      alleles/genotype of this genetic variant was statistically associated with glioma
      risk. The AA genotype was statistically associated with the increased risk of
      glioma compared to the GG wild genotype (odds ratios (OR) = 1.89, 95% CI 1.25
      2.87, P = 0.003). The allele-A may contribute to increased the susceptibility to
      glioma (OR = 1.23, 95% CI 1.04-1.46, P = 0.017). CONCLUSIONS: These preliminary
      findings indicate that the c.1471G>A genetic polymorphism of XRCC1 has the
      potential to influence glioma susceptibility, and might be used as molecular
      marker for assessing glioma risk.

PMID- 24289609
TI  - Risk factors of breast cancer in kyzylorda oblast of Kazakhstan: a case-control
      study.
AB  - BACKGROUND: Breast cancer in Kazakhstan and its Kyzylorda oblast is the most
      prevalent cancer in women and features increasing trends of incidence. The aim of
      study was to reveal risk factors for breast cancer among women of Kyzylorda
      oblast of Kazakhstan. MATERIALS AND METHODS: A hospital-based case-control study
      was conducted at Kyzylorda oblast Oncology Center, including 114 cases of breast
      cancer and 196 controls. Binary logistic regression analysis was performed.
      RESULTS: Social and behavioral risk factors for breast cancer were evaluated,
      among which unfavorable living conditions, chronic stress, unilateral
      breastfeeding, breastfeeding less than 3 months and over 2 years, abortions, and
      hereditary predisposition were found to be related with increased breast cancer
      risk. Breastfeeding for 6-24 months was found to be protective. CONCLUSIONS: The
      findings may have significant impact on activity planning aimed towards breast
      cancer reduction among women in Kazakhstan.

PMID- 24289610
TI  - Pin1 promoter rs2233678 and rs2233679 polymorphisms in cancer: a meta-analysis.
AB  - PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed
      phosphorylation, PIN1 plays an important role in cell transformation and
      oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678
      and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control
      studies were conducted to investigate the association between PIN1 gene rs2233678
      and rs2233679 polymorphism and cancer risk. However, published data are still
      conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469
      controls from 9 studies and attempted to assess the susceptibility of PIN1 gene
      polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were estimated to assess the relationship. All
      analyses were performed using Stata software. Our results suggested that
      rs2233678 represented a protective factor in overall analysis (CC vs GG: OR=
      0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant
      model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI:
      0.623-0.867) and especially for squamous cell carcinoma of the head and neck,
      lung cancer and breast cancer in Asians and Caucasians. The rs2233679
      polymorphism was significantly associated with decreased cancer risk in overall
      analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893,
      95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and
      especially in Asians. In conclusion, our meta-analysis suggested that -842G>C
      (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for
      cancer risks. Further prospective research with larger numbers of worldwide
      participants is warranted to draw comprehensive and firm conclusions. 

PMID- 24289611
TI  - In silico design of discontinuous peptides representative of B and T-cell
      epitopes from HER2-ECD as potential novel cancer peptide vaccines.
AB  - At present, the most common cause of cancer-related death in women is breast
      cancer. In a large proportion of breast cancers, there is the overexpression of
      human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa
      growth factor glycoprotein, also known as the first tumor-associated antigen for
      different types of breast cancers. Moreover, HER2 is an appropriate cell-surface
      specific antigen for passive immunotherapy, which relies on the repeated
      application of monoclonal antibodies that are transferred to the patient.
      However, vaccination is preferable because it would stimulate a patient's own
      immune system to actively respond to a disease. In the current study, several
      bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP
      was used to predict peptides from HER2 ECD subdomain III in the form of
      discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web
      servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were
      used to identify class-I and II MHC peptides. In this way, PEPOP selected 12
      discontinuous peptides from the 3D structure of the HER2 ECD subdomain III.
      Furthermore, T-cell epitope prediction analyses identified four peptides
      containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell
      epitopes. This work is the only study to our knowledge focusing on design of in
      silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that
      contain epitopes for both B and T-cells. These findings based on bioinformatics
      analyses may be used in vaccine design and cancer therapy; saving time and
      minimizing the number of tests needed to select the best possible epitopes. 

PMID- 24289612
TI  - Radix tetrastigma hemsleyani flavone induces apoptosis in human lung carcinoma
      a549 cells by modulating the MAPK pathway.
AB  - Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb
      for its detoxification and anti-inflammation activity. Recently, several studies
      have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell
      lines. However, the mechanisms are not completely understood yet. In this study
      we investigated the potential effects of RTHF on growth and apoptosis in human
      lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated
      with RTHF at various concentrations for different times. In vitro the MTT assay
      showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose-
      and time- dependent manner. Cell morphological changes observed by inverted
      microscope and Hoechst33258 methods were compared with apoptotic changes observed
      by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed
      significant increase in the treatment group over the control group (P<0.01).
      Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins
      were detected by Western blotting. The results showed that RTHF up-regulated the
      Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose- dependent
      manner. Expression of p-p38 increased, p-ERK decreased significantly and that of
      p-JNK was little changed in the RTHF group when compared with the control group.
      These results suggest that RTHF might exert anti-growth and apoptosis activity
      against lung cancer A549 cells through activation of caspases and Bcl-2 family
      proteins and the MAPK pathway, therefore presenting as a promising therapeutic
      agent for the treatment of lung cancer. 

PMID- 24289614
TI  - Nausea and vomiting after transcatheter arterial chemoembolization for
      hepatocellular carcinoma: incidence and risk factor analysis.
AB  - BACKGROUND: Nausea and vomiting after transcatheter arterial chemoembolization
      (TACE) for hepatocellular carcinoma (HCC) are common in clinical practice, but
      few studies have reported the incidence and risk factors of such events.
      OBJECTIVE: The purpose of this study was to analyze the incidence and risk
      factors of nausea and vomiting after TACE for HCC. METHODS: This study was a
      single-center retrospective analysis of a prospectively maintained database.
      Between May 2010 and October 2012, 150 patients with HCC were analyzed for
      incidence and preprocedural risk factors. RESULTS: The incidence of
      postembolization nausea and vomiting was 38.8% and 20.9%, respectively, in
      patients with HCC. Patients who developed nausea had lower levels (<100 IU/L) of
      serum alkaline phosphatase (ALP) compared to those without nausea (123.04 +/-
      69.38 vs. 167.41 +/- 138.95, respectively, p=0.044). Female gender correlated to
      a higher incidence of nausea as well (p=0.024). Patients who developed vomiting,
      compared to those who did not, also had lower levels (<100 IU/L) of serum ALP
      (112.52 +/- 62.63 vs. 160.10 +/- 127.80, respectively, p=0.010), and serum
      alanine transferase (ALT) (35.61 +/- 22.87 vs. 44.97 +/- 29.62, respectively,
      p=0.045). There were no statistical significances in the incidences of nausea and
      vomiting between male patients over 50 years old and female patients who have
      entered menopause (p=0.051 and p=0.409, respectively). Multivariate analysis by
      logistic regression analysis demonstrated that female gender and ALP>100 IU/L
      were the most independent predictive factors of postembolization nausea (odds
      ratio (OR): 3.271, 95% CI: 1.176-9.103, p=0.023 and OR: 0.447, 95% CI: 0.216
      0.927, p=0.030, respectively). ALP>100 IU/L was also the most independent
      predictive risk factor of postembolization vomiting (OR: 0.389, 95% CI: 0.159
      0.952, p=0.039). CONCLUSIONS: Postembolizaiton nausea and vomiting are common in
      patients with HCC. Recognition of the risk factors presented above before TACE is
      important for early detection and proper management of postembolization nausea
      and vomiting. Nevertheless, future studies are required.

PMID- 24289613
TI  - Plan dose evaluation of three dimensional conformal radiotherapy planning (3D
      CRT) of nasopharyngeal carcinoma (NPC): experience of a tertiary care University
      Hospital in Pakistan.
AB  - BACKGROUND: Radiation therapy is the mainstay of treatment for nasopharyngeal
      carcinoma. Importance of tumor coverage and challenges posed by its unique and
      critical location are well evident. Therefore we aimed to evaluate our radiation
      treatment plan through dose volume histograms (DVHs) to find planning target
      volume (PTV) dose coverage and factors affecting it. MATERIALS AND METHODS: This
      retrospective study covered 45 histologically proven nasopharyngeal cancer
      patients who were treated with definitive 3D-CRT and chemotherapy between Feb
      2006 to March 2013 at the Department of Oncology, Section Radiation Oncology ,Aga
      Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of
      shrinking field (phases), PTV volume in different phases and its coverage by the
      95% isodose lines, along with influencing factors. RESULTS: There were 36 males
      (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was
      the most common stage followed by stage III (31.1). Eighty six point six-percent
      received induction, 95.5% received concurrent and 22.2% received adjuvant
      chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to
      clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean
      dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point
      eight-percent patients completed their treatment in three phases while 62.2%
      required four to five phases. Mean volume for PTV3 was 247.8 cm3 (50-644.3), PTV4
      173.8 cm3 (26.5-345.1) and PTV5 119.6 cm3 (18.9-246.1) and PTV volume coverage by
      95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage,
      intracranial extension and tumor volume >200 cm3 were found to be important
      factors associated with decreased PTV coverage by 95% isodose line. CONCLUSIONS:
      3D CRT results in adequate PTV dose coverage by 95% isodose line. However
      advanced T stage, intracranial extension and large target volume require more
      advanced techniques like IMRT for appropriate PTV coverage.

PMID- 24289615
TI  - Anti-cell proliferative and anti-angiogenic potential of andrographolide during
      7,12- dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.
AB  - Our aim was to explore anti-cell proliferative and anti-angiogenic potential of
      andrographolide by analyzing the expression pattern of cell proliferative (PCNA,
      Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene
      (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a
      week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral
      tumors which were histopathologically diagnosed as well differentiated squamous
      cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies
      revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of
      hamsters treated with DMBA alone. Oral administration of andrographolide at a
      dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the
      histological abnormalities but also down regulated the expression of PCNA, VEGF
      and Cyclin D1. The results of the present study suggest that andrographolide
      suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA
      through its anti-cell proliferative and anti-angiogenic potential. 

PMID- 24289616
TI  - ANXA2 regulates the behavior of SGC-7901 cells.
AB  - ANXA2, a member of the annexin family, is overexpressed and plays important roles
      in tumor development. However, the significance of ANXA2 expression in gastric
      carcinoma has not been clarified.To elucidate its roles in growth of gastric
      cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA,
      then cell proliferation, cell cycling, apoptosis and motility were determined by
      MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay,
      respectively. To further assess the behavior of ANXA2 deleted SGC- 7901 cells,
      changes of microstructures were observed under fluorescence microscopy, laser
      scanning confocal microscopy and electron microscopy. We found that inhibition of
      ANXA2 expression caused cell proliferation to decrease significantly with G1
      arrest, motility to be reduced with changes in pseudopodia/filopodia structure
      and F-actin and beta-tubulin expression, and apoptosis to be enhanced albeit
      without significance. At the same time, ANXA2 deletion resulted in fewer
      pseudopodia/filopodia, non-stained areas were increased, contact inhibition among
      cells reappeared, and expression of F-actin and beta-tubulin was decreased, with
      induction of polymerized disassembled forms. Taken together, these data suggest
      that ANXA2 overexpression is important to maintain the malignancy of cancer
      cells, and this member of the annexin family has potential to be considered as a
      target for the gene therapy of gastric carcinoma. 

PMID- 24289617
TI  - Clinicopathologic and demographic evaluation of triple- negative breast cancer
      patients among a turkish patient population: a single center experience.
AB  - BACKGROUND: To evaluate the clinicopathologic and demographic characteristics of
      triple-negative breast cancer (TNBC) patients and to determine differences from
      non-triple-negative cases. MATERIALS AND METHODS: A detailed review of the
      medical records of 882 breast cancer (BC) patients was conducted to obtain
      information regarding age, menopausal status, height and weight at the time of
      diagnosis, presence of diabetes or hypertension, and pathologic characteristics
      of the tumor (tumor size, lymph node status, histologic grade, ER status, PR
      status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a
      value of >=30 was considered as indicative of obesity. RESULTS: 14.9% (n=132) of
      the patients had TNBC. There was no difference among the patients in terms of
      median age, comorbid conditions and menopausal status. The proportion of
      medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in
      the triple-negative (TN) group, while invasive lobular histology was more
      frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3)
      tumors were more frequent in the triple-negative group (p<0.001). The rate of p53
      mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two
      groups were similar in terms of LN metastasis. In the NTN group, the rate of
      patients with BMI >=30 was 53% among postmenopausal patients, while it was 36%
      among premenopausal women, and the difference was statistically significant
      (p<0.001). No significant difference was observed in terms of BMI between
      postmenopausal and premenopausal patients in the TN group (p=0.08). CONCLUSIONS:
      TNBC rates and clinicopathologic characteristics of the Turkish patient
      population were consistent with the data from Europe and America. However, no
      relationship between obesity and TNBC was observed in our study. The association
      between TNBC and obesity needs to be evaluated in a larger patient population.

PMID- 24289618
TI  - Prediction models for solitary pulmonary nodules based on curvelet textural
      features and clinical parameters.
AB  - Lung cancer, one of the leading causes of cancer-related deaths, usually appears
      as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked
      eye. In this paper, curvelet-based textural features and clinical parameters are
      used with three prediction models [a multilevel model, a least absolute shrinkage
      and selection operator (LASSO) regression method, and a support vector machine
      (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality
      reduction of the original curvelet-based textural features was achieved using
      principal component analysis. In addition, non-conditional logistical regression
      was used to find clinical predictors among demographic parameters and
      morphological features. The results showed that, combined with 11 clinical
      predictors, the accuracy rates using 12 principal components were higher than
      those using the original curvelet-based textural features. To evaluate the
      models, 10-fold cross validation and back substitution were applied. The results
      obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and
      0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it
      was found that using curvelet-based textural features after dimensionality
      reduction and using clinical predictors, the highest accuracy rate was achieved
      with SVM. The method may be used as an auxiliary tool to differentiate between
      benign and malignant SPNs in CT images. 

PMID- 24289619
TI  - Matrix metalloproteinase-2 (-1306 c>t) promoter polymorphism and risk of
      colorectal cancer in the Saudi population.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic
      activity against matrix proteins, particularly basement membrane constituents. A
      single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter
      site (CCACC box), results in strikingly lower promoter activity with the T
      allele. In the present study, we investigated whether this MMP-2 genetic
      polymorphism might be associated with susceptibility to colorectal cancer (CRC)
      in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC
      patients and 4 different cancer cell lines. MATERIALS AND METHODS: TaqMan allele
      discrimination assays and DNA sequencing techniques were used to investigate the
      C-1306T SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls.
      The MMP-2 gene expression level was also determined in 12 colon cancer tissue
      samples collected from unrelated patients and histologically normal tissues
      distant from tumor margins. RESULTS AND CONCLUSIONS: The MMP-2 C-1306T SNP in the
      promoter region was associated with CRC in our Saudi population and the MMP-2
      gene expression level was found to be 10 times higher in CRC patients. The MMP-2
      C-1306T SNP is significantly associated with CRC in the Saudi population and this
      finding suggested that MMP-2 variants might help predict CRC progression risk
      among Saudis. We propose that analysis of this gene polymorphism could assist in
      identification of patient subgroups at risk of a poor disease outcome.

PMID- 24289620
TI  - Incidence, survival and prevalence of esophageal and gastric cancer in Linzhou
      city from 2003 to 2009.
AB  - This study describes recent trends in incidence, survival and prevalence of
      subgroups of esophageal and gastric cancer in Linzhou city between 2003 and 2009.
      Data of esophageal and gastric cancer for the period of interest were extracted
      from the Linzhou Cancer Registry. Using information on tumor morphology or
      anatomical site, data were divided into six groups; esophageal squamous cell
      carcinoma, esophageal adenocarcinoma, other and unspecified types of esophageal
      cancer, and cardia, non-cardia, and unspecified anatomical site of stomach
      cancer. Incidence, survival and prevalence rates for each of the six cancer
      groups were calculated. The majority of esophageal cancers were squamous cell
      carcinomas (82%). Cardiac cancer was the major gastric cancer group (64%). The
      incidence of esophageal squamous cell carcinoma and gastric cardiac cancer
      increased between 2003 and 2009. Both esophageal and gastric cancer had a higher
      incidence in males compared with females. Overall survival was poor in all sub
      groups with 1 year survival ranging from 45.9 to 65.6% and 5 year survival
      ranging from 14.7 to 30.5%. Prevalence of esophageal squamous cell carcinoma and
      gastric cardiac cancer was high (accounting for 80% overall). An increased focus
      on prevention and early diagnosis, especially in esophageal squamous cell
      carcinoma and gastric cardiac cancer, is required. 

PMID- 24289621
TI  - Comparison of population based cancer incidence rates among Circassians, Chechans
      and Arabs in Jordan (1996-2005).
AB  - BACKGROUND: Cancer is a complex disease caused by multiple factors, both genetic
      and environmental. It is a major health concern worldwide, in the Middle East and
      in Jordan specifically and the fourth most common killer in the Middle East.
      HYPOTHESIS: The relative genetic homogeneity of the Circassian and Chechan
      populations in Jordan results in incidences of cancer that differ from the
      general Jordanian population, who are mostly Arabs. MATERIALS AND METHODS:
      National Cancer Registry data were obtained for the years 1996-2005 The Chechen
      and Circassian cancer cases were identified and cancer registry data were divided
      into three populations. Crude rates were calculated based on the number of cancer
      cases and estimated populations. RESULTS: Breast cancer is the most common cancer
      type constituting about one third of female cancers in all three populations.
      Higher crude rates are observed in the Circassian and Chechen populations than in
      the Arab Jordanian population. The rate ratios (95%CI) in Circassians and
      Chechens with respect to the Arab Jordanian population are 2.1 (1.48, 2.72) and
      1.81 (1.16, 2.85), respectively. Lung cancer is the most common cancer in male
      Arab Jordanians and Chechens with crude rates of 4.2 and 8.0 per 100,000
      respectively. The male to female ratio in these two populations in respective
      order are 5:1 and 7:1. The lung cancer crude rate in Circassians is 6.5 per
      100,000 with a male to female ratio of only 1.6:1. The colorectal cancer crude
      rates in Arab Jordanians and Chechens are similar at 6.2 and 6.0 per 100,000,
      respectively, while that in Circassians is twice as high. CONCLUSIONS:
      Considerable ethnic variation exists for cancer incidence rates in Jordan. The
      included inbred and selected populations offer an ideal situation for
      investigating genetic factors involved in various cancer types.

PMID- 24289622
TI  - Factors affecting breast cancer screening behavior in Japan--assessment using the
      health belief model and conjoint analysis.
AB  - BACKGROUND: Japanese women in their 40s or older have been encouraged to attend
      breast cancer screening. However, the breast cancer screening rate in Japan is
      not as high as in Europe and the United States. The aim of this study was to
      identify psychological and personal characteristics of women concerning their
      participation in breast cancer screening using the Health Belief Model (HBM). In
      addition, the attributes of screening more easily accepted by participants were
      analyzed by conjoint analysis. MATERIALS AND METHODS: In this cross sectional
      study of 3,200 age 20-69 women, data were collected by an anonymous
      questionnaire. Questions were based on HBM and personal characteristics, and
      included attitudes on hypothetical screening attributes. Data of women aged 40-69
      were analyzed by logistic regression and conjoint analysis to clarify the factors
      affecting their participation in breast cancer screening. RESULTS: Among
      responses collected from 1,280 women of age 20-69, the replies of 993 women of
      age 40-69 were used in the analysis. Regarding the psychological characteristics
      based on HBM, the odds ratios were significantly higher in "importance of cancer
      screening" (95%CI: 1.21-2.47) and "benefits of cancer screening" (95%CI: 1.09
      2.49), whereas the odds ratio was significantly lower in "barriers to
      participation before cancer screening" (95%CI: 0.27-0.51). Conjoint analysis
      revealed that the respondents, overall, preferred screening to be low cost and by
      female staff members. Furthermore, it was also clarified that attributes of
      screening dominant in decision-making were influenced by the employment status
      and the type of medical insurance of the women. CONCLUSIONS: In order to increase
      participation in breast cancer screening, it is necessary to disseminate accurate
      knowledge on cancer screening and to reduce barriers to participation. In
      addition, the attributes of screening more easily accepted were inexpensive,
      provided by female staff, executed in a hospital and finished in a short time.

PMID- 24289623
TI  - High incidence of benign brain meningiomas among Iranian- born Jews in Israel may
      be linked to both hereditary and environmental factors.
AB  - BACKGROUND: Following research demonstrating an increased risk for meningiomas in
      the Jewish population of Shiraz (Iran) we conducted a cohort analysis of
      meningiomas among Jews originating in Iran and residing in Israel. MATERIALS AND
      METHODS: We use the population-based registry data of the Israeli National Cancer
      Registry (INCR) for the main analysis. All benign meningioma cases diagnosed in
      Israel from January 2000 to the end of 2009 were included. Patients that were
      born in Iran, Iraq, Turkey, Bulgaria and Greece were used for the analysis,
      whereby we calculated adjusted incidence rates per 100,000 people and computed
      standardized incidence ratios (SIRs) comparing the Iranian-born to each of the
      three other groups. RESULTS: Iranian-born Jews had statistically significant
      higher meningioma rates rates compared to other Jews originating in Balkan
      states: 1.46 fold compared to Turkish Jews and 1.86 fold compared to the Bulgaria
      Greece group. There was a small increase in risk for the Iranian born group
      compared to those who were born in Iraq (1.06, not significant). CONCLUSIONS:
      Higher rates of meningiomas were seen in Jews originating in Iran that are living
      in Israel as compared to rates in neighboring countries of origin. These
      differences can be in part attributed to early life environmental exposures in
      Iran but probably in larger amount are due to genetic and hereditary factors in a
      closed community like the Iranian Jews. Some support for this conclusion was also
      found in other published research.

PMID- 24289624
TI  - Determining the knowledge of women and their attitudes regarding gynecological
      cancer prevention.
AB  - The current study determines the knowledge of female course attendees of the
      "Municipality Cultural Center for Women", located in the city center of Sivas,
      Turkey, and their attitudes regarding gynecological cancer prevention. The
      participants of the study include 497 women attending one of the two Municipality
      Cultural Centers situated in the city center of Sivas. In this study, the sample
      was not selected; all participants were encompassed within the scope of our
      research. A total of 418 female course attendees who volunteered to participate
      in the research were identified as the sample. The data were collected during the
      months March-June 2011, by a questionnaire developed by the researchers. To
      compare the distribution of the collected data "Anova", "two independent t test
      examples" and "chi square test" were used. The research indicates that 45.1% of
      the women had had gynecological examination as a consequence of a physical
      disorder. The reason for 54.9% of the women to have gynecological examination is
      to have been scanned to check for gynecological cancer, 51.2% had a pap smear
      test. Some 34.9% of them had obtained information about cervical cancer, 39.7%
      via radio, television or internet and 36.3% from a doctor. Age, education level
      and marital status of the women participating in this study demonstrated
      statistically significant correlations (p<0.05) with gynecological examination
      and undergoing a pap smear test. 

PMID- 24289625
TI  - Pulmonary lobectomy combined with pulmonary arterioplasty by complete video
      assisted thoracic surgery in patients with lung cancer.
AB  - OBJECTIVE: To explore the feasibility of pulmonary lobectomy combined with
      pulmonary arterioplasty by complete video-assisted thoracic surgery (VATS) in
      patients with lung cancer, and summarize its surgical methods. MATERIALS AND
      METHODS: Twenty-one patients with lung cancer in Beijing Chest Hospital
      Affiliated to Capital Medical University from Feb., 2010 to Jun., 2013 were
      selected, males and females accounting for 15 and 6 cases, respectively. Ten
      underwent right upper lobectomy, 5 right lower lobectomy, 4 left upper lobectomy
      (in which left upper sleeve lobectomy was conducted for 2) and 2 left lower
      lobectomy. At the same time, local resection of pulmonary arterioplasty was
      performed for 12 patients, and sleeve resection of pulmonary arterioplasty for 9.
      RESULTS: Twenty-one patients recovered well after surgery. Thoracic drainage tube
      was maintained for 3-8 days, with an average of 4.9 days, and hospital stays were
      8-15 days, with an average of 11 days. There were no deaths in the perioperative
      period, and the complications like pulmonary embolism, bronchopleural fistula,
      chest infection and pulmonary atelectasis did not occur after surgery.
      CONCLUSIONS: Performance of pulmonary lobectomy and pulmonary arterioplasty
      together by complete VATS is a safe and effective surgical method, which can
      expand the indications of patients with lung cancer undergoing thoracoscopic
      pulmonary lobectomy, and make more patients profit from such minimally invasive
      treatment.

PMID- 24289626
TI  - Increase in the rate of HPV positive oropharyngeal cancers during 1996-2011 in a
      case study in Turkey.
AB  - BACKGROUND: Primary aim of this study is to assess whether or not there is an
      increase at rate of HPV positive oropharyngeal cancers during 1996-2011 in
      Turkey, for comparison with prior reports from Western countries. MATERIALS AND
      METHODS: A total of 138 newly diagnosed patients with oropharyngeal cancer were
      identified, 39 of which had no primary tumor specimen available and 18 patients
      with invalid HPV status, therefore HPV status for remaining 81 patients was
      evaluated. The presence and type of HPV DNA were determined with formalin- fixed
      paraffin embedded specimens, using an HPV DNA-based multiplex PCR assay.
      Associations between HPV status and clinicopathological characteristics were
      evaluated using a two-sample t-test for the continuous variables and the
      categorical variables were compared by chi-square test. Overall survival (OS)
      periods were calculated with Kaplan-Meier method. RESULTS: The proportion of HPV
      positive cancer has continued to increase during 2004-2011 as compared with 1996
      2003. Notably, 33% (6/18) of the cases were HPV-positive in 1996-1999, 43% (9/21)
      in 2000-2003, 55% (11/20) in 2004-2007 and 70% (16/23) in 2008-2011. Thus, when
      we compared the results obtained during the 2004-2011with results of 1996-2003
      period, we found that increase at HPV-positivity ratio was statistically
      significant (38% vs 64% p=0.012). CONCLUSIONS: This study demonstrated that HPV
      positive oropharyngeal cancers are increasing in Turkish patients as in the
      Western world.

PMID- 24289627
TI  - Comparative serum proteomic analysis of serum diagnosis proteins of colorectal
      cancer based on magnetic bead separation and maldi-tof mass spectrometry.
AB  - BACKGROUND: At present, the diagnosis of colorectal cancer (CRC) requires a
      colorectal biopsy which is an invasive procedure. We undertook this pilot study
      to develop an alternative method and potential new biomarkers for diagnosis, and
      validated a set of well-integrated tools called ClinProt to investigate the serum
      peptidome in CRC patients. METHODS: Fasting blood samples from 67 patients
      diagnosed with CRC by histological diagnosis, 55 patients diagnosed with
      colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division
      was into a model construction group and an external validation group randomly.
      The present work focused on serum proteomic analysis of model construction group
      by ClinProt Kit combined with mass spectrometry. This approach allowed
      construction of a peptide pattern able to differentiate the studied populations.
      An external validation group was used to verify the diagnostic capability of the
      peptidome pattern blindly. An immunoassay method was used to determine serum CEA
      of CRC and controls. RESULTS: The results showed 59 differential peptide peaks in
      CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to
      set up the classification models. Four of the identified peaks at m/z 797, 810,
      4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of
      100% (> CEA, P < 0. 05). Furthermore, the peptidome patterns could differentiate
      the validation group with high accuracy close to 100%. CONCLUSIONS: Our results
      showed that proteomic analysis of serum with MALDI-TOF MS is a fast and
      reproducible approach, which may provide a novel approach to screening for CRC.

PMID- 24289628
TI  - Awareness and knowledge about human papillomavirus infection and vaccination
      among women in UAE.
AB  - BACKGROUND: Cervical cancer is the second commonest female cancer worldwide. The
      50-55 cases of cervical cancer are reported annually in the UAE. There is a
      scarcity of data from Middle Eastern region regarding knowledge and attitude of
      women towards HPV infection, cervical cancer prevention and HPV vaccine. The aim
      of our study was to assess the knowledge of women regarding HPV infection and
      vaccine in UAE. MATERIALS AND METHODS: A cross-sectional survey of 640 women aged
      18-50 years was conducted in Al-Ain district in UAE using convenience sampling.
      Women with previous diagnosis of cervical cancer, non- residents of UAE, younger
      than 18 or older than 50 years of age and those unable to speak Arabic or English
      were excluded from the study. Logistic regression analysis was performed to
      assess the association of HPV knowledge with independent factors like age,
      education etc. RESULTS: Only 29% of our sampled women have ever heard of HPV
      infection. Only 15.3% women recognized it as STI. Only about 22% women have also
      heard of the HPV vaccine. Three quarter of the women in our study thought that
      cervical cancer can be prevented. About 28% recognized vaccine as a preventive
      measure against cervical cancer. Age (AOR 1.049, 95%CI 1.02-1.08) and husband's
      level of education were found to be significant (p value 0.015) after adjusting
      for women's age. CONCLUSIONS: The knowledge of HPV infection and vaccine is low
      in the UAE. Few women recognized HPV as sexually transmitted infection.
      Increasing age and husband's education are associated with better knowledge of
      HPV infection.

PMID- 24289630
TI  - Impact of PSA and DRE on histologic findings at prostate biopsy in Turkish men
      over 75 years of age.
AB  - Prostate specidic antigen (PSA) and digital rectal examination (DRE) are the
      known predictive factors for positive prostate biopsies differing according to
      the age, region and race. There have been only very limited studies about the
      impact of PSA on histological findings at prostate biopsy in Turkey. The aim of
      this study was to evaluate the impact of PSA and clinical stage on histologic
      findings of prostate biopsy in men older than 75 years of age as a first study in
      the Turkish population. A total of 1,645 consecutive prostate biopsies were
      included, with 194 men aged 75 or older. Cancer was identified in 104 patients
      (53.6%). Of the 104 positive biopsies, Gleason scores were less than 7 in 53
      (49%) patients, 7 or greater in 51 (51%) patients. Positive prostate biopsies
      were significantly correlated with advanced age (p=0.0001), abnormal DRE
      (p=0.0001) and raised PSA (p=0.0001). The prostate volume was significantly
      correlated with advanced age especially in prostate cancer patients over 75
      years, compared with those under 75 (p=0.0001). These results are useful for
      counseling men older than 75 years for prostate cancer detection. However, PCa
      screening decisions are currently based on urologist judgment and detection of
      latent asymptomatic disease is an important concern regarding costs,
      overdiagnosis, overtreatment and quality of life (QOL) for men aged 75 years and
      older. Healthy old patients with a long life expectancy need to be carefully
      evaluated for eligibility for PCa screening. 

PMID- 24289629
TI  - Prognostic significance of interactions between ER alpha and ER beta and lymph
      node status in breast cancer cases.
AB  - OBJECTIVE: Both estrogen receptors, ER alpha (ERalpha) and ER beta (ERbeta), are
      expressed in 50-70% of breast cancer cases. The role of ERalpha as a prognostic
      marker in breast cancer has been well established as its expression is negative
      correlated with tumor size and lymph node metastasis. ERbeta is also a favorable
      prognostic predictor although this is less well documented than for ERalpha.
      MATERIALS AND METHODS: To explore whether ERs independently or together might
      influence clinical outcome in breast cancer, the correlation between the ERs with
      the clinicopathological features was analyzed in 84 patients. RESULTS: ERalpha
      expression negatively correlated with tumor stage (r=-0.246, p=0.028) and tended
      to be negatively correlated with lymph node status (r=-0.156, p=0.168) and tumor
      size (r=-0.246, p=0.099). Also, ERbeta was negatively correlated with nodal
      status (r=-0.243, p=0.028), as was coexpression of ERalpha and ERbeta (p=0.043,
      OR=0.194, 95% CI= 0.040- 0.953). CONCLUSION: Coexpression of ERs might serve as
      an indicator of good prognosis in breast cancer patients.

PMID- 24289631
TI  - Genomic screening for targets regulated by berberine in breast cancer cells.
AB  - Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer
      activities. However, the underlying molecular mechanisms are still not completely
      understood. In the current study, we investigated the effects of berberine on
      cell growth, colony formation, cell cycle distribution, and whether it improved
      the anticancer efficiency of cisplatin and doxorubicin in human breast cancer
      estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-)
      MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell
      growth and colony formation in the two cell lines, berberine in combination with
      cisplatin exerting synergistic growth inhibitory effects. Accompanied by
      decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231
      cells. To provide a more detailed understanding of the mechanisms of action of
      berberine, we performed genome-wide expression profiling of berberine-treated
      cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes
      regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology
      (GO) analysis identified that many of the target genes were involved in
      regulation of the cell cycle, cell migration, apoptosis, and drug responses. To
      confirm the microarray data, qPCR analysis was conducted for 10 selected genes
      based on previously reported associations with breast cancer and GO analysis. In
      conclusion, berberine exhibits inhibitory effects on breast cancer cells
      proliferation, which is likely mediated by alteration of gene expression
      profiles. 

PMID- 24289632
TI  - Relationship between Social Network and Stage of Adoption of Gastric Cancer
      Screening among the Korean Population.
AB  - Few studies have examined the relationship between social support and stages of
      adoption of cancer screening. Here we investigated associations between both
      structural and functional aspects of social support and stages of adoption of
      gastric cancer screening in the general population of Korea. The study population
      was derived from the 2011 Korean National Cancer Screening Survey (KNCSS), an
      annual cross-sectional survey that uses nationally representative random sampling
      to investigate cancer screening rates. Data were analyzed from 3,477 randomly
      selected respondents aged 40-74 years. Respondents were classified according to
      their stage of adoption of gastric cancer screening: precontemplation (13.2%),
      contemplation (18.0%), action/maintenance (56.1%), relapse risk (8.5%), and
      relapse stage (4.1%). Respondents with larger social networks were more likely to
      be in the contemplation/action/maintenance, or the relapse risk/relapse stages
      versus the precontemplation stage (OR=1.91, 95%CI: 1.52-2.91; p for tend=0.025).
      Emotional and instrumental supports were not associated with any stage of
      adoption of gastric cancer screening. However, respondents who reported receiving
      sufficient informational support were more likely to be in the relapse
      risk/relapse stages versus the precontemplation, or the
      contemplation/action/maintenance stage (p for trend=0.016). Interventions
      involving interactions between social network members could play an important
      role in increasing participation in gastric cancer screening. 

PMID- 24289633
TI  - The DNA repair gene ERCC6 rs1917799 polymorphism is associated with gastric
      cancer risk in Chinese.
AB  - OBJECTIVE: Excision repair cross-complementing group 6 (ERCC6) is a major
      component of the nucleotide excision repair pathway that plays an important role
      in maintaining genomic stability and integrity. Several recent studies suggested
      a link of ERCC6 polymorphisms with susceptibility to various cancers. However,
      the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive.
      In this sex- and age- matched case-control study including 402 GC cases and 804
      cancer-free controls, we aimed to investigate the association between a
      potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory
      region and GC risk. METHODS: The genotypes of rs1917799 were determined by
      Sequenom MassARRAY platform and the status of Helicobacter pylori infection was
      detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95%
      confidential interval (CI) were calculated by logistic regression analysis.
      RESULTS: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype
      was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08,
      P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated
      a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01
      1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT:
      adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted
      OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended
      to be enhanced by H. pylori infection, smoking and drinking, but their
      interaction effects on GC risk did not reach statistical significance.
      CONCLUSIONS: ERCC6 rs1917799 GG genotype might be associated with increased GC
      risk in Chinese, especially in males.

PMID- 24289634
TI  - Does beta-blocker therapy improve the survival of patients with metastatic non
      small cell lung cancer?
AB  - AIM: To determine whether beta-blockers (BBs) improve the overall survival (OS)
      of patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: The medical charts of 107 patients with metastatic NSCLC were
      retrospectively assessed. Thirty-five patients (BB group) using BBs during
      chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not
      use BBs following the diagnosis of NSCLC. The histological tumor subtype,
      performance status (ECOG), age, gender, smoking status, comorbidities, other
      medications and chemotherapeutics that were received in any line of treatment
      were recorded. We compared the overall survival (OS) of the patients in the BB
      and C groups. RESULTS: The mean age of the patients was 61 years (range 42-81
      years) and all patients were administered CT. The BB group was more likely to
      have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared
      with the C group, as expected. The mean follow-up time was 17.8 months (range 1
      102 months) for the entire group. The most commonly prescribed BB agent was
      metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients
      had died. In the univariate analysis the median overall survival (OS) was 19.25
      (+/-2.87) months (95%CI: 13.62-24.88) in the BB group and 13.20 (+/-2.37) months
      (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on
      survival disappeared in the multivariate analysis. CONCLUSIONS: The use of BBs
      during CT may be associated with an improved OS for patients with metastatic
      NSCLC.

PMID- 24289635
TI  - Effect of Embelin on TRAIL receptor 2 mAb-induced apoptosis of TRAIL-resistant
      A549 non-small cell lung cancer cells.
AB  - INTRODUCTION: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive
      to tumor necrosis factor- related apoptosis-inducing ligand (TRAIL) -based
      therapy. This study was conducted to examine the effect of embelin on the
      sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal
      antibodies and to investigate the potential mechanisms. MATERIALS AND METHODS:
      A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell
      viability was measured using ATPlite assay and apoptosis rates were determined by
      flow cytometry with AnnexinV-FITC and propidium iodide staining, with the
      expression levels of proteins analyzed by Western blotting. RESULTS: The cell
      survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM
      embelin were 81.5+/-1.57% and 61.7+/-2.84%, respectively. Their combined use
      markedly decreased cell viability in A549 cells to 28.1+/-1.97% (P<0.05). The
      general caspase inhibitor Z-VAD- FMK could inhibit the embelin-enhanced
      sensitivity of A549 cells to TRAILR2 mAb (75.97+/-3.17%)(P<0.05). Both flow
      cytometry and cell morphological analysis showed that embelin was able to
      increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin
      and TRAILR2 mAb augmented the activation of initiator caspases and effector
      caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and
      decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with
      embelin+TRAILR2 mAb. CONCLUSIONS: Embelin could enhance TRAIL-induced apoptosis
      in A549 cells. The synergistic effect of the combination treatment might be due
      to modulation of multiple components in the TRAIL receptor-mediated apoptotic
      signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.

PMID- 24289636
TI  - Which endometrial pathologies need intraoperative frozen sections?
AB  - BACKGROUND: Endometrial cancers are the most common gynecologic cancers.
      Endometrial sampling is a preferred procedure for diagnosis of the endometrial
      pathology. It is performed routinely in many clinics prior to surgery in order to
      exclude an endometrial malignancy. We aimed to investigate the accuracy of
      endometrial sampling in the diagnosis of endometrial pathologies and which
      findings need intra-operative frozen sections. MATERIALS AND METHODS: Three
      hundred nine women applying to a university hospital and undergoing endometrial
      sampling and hysterectomy between 2010 and 2012 were included to this
      retrospective study. Data were retrieved from patient files and pathology
      archives. RESULTS: There was 17 patients with malignancy but endometrial sampling
      could detect this in only 10 of them. The endometrial sampling sensitivity and
      specificity of detecting cancer were 58.8% and 100%, with negative and positive
      predictive values of 97.6%, and 100%, respectively. In 7 patients, the
      endometrial sampling failed to detect malignancy; 4 of these patients had a
      preoperative diagnosis of complex atypical endometrial hyperplasia and 2 patients
      had a post-menopausal endometrial polyps and 1 with simple endometrial
      hyperplasia. CONCLUSIONS: There is an increased risk of malignancy in post
      menopausal women especially with endometrial polyps and complex atypia
      hyperplasia. Endometrial sampling is a good choice for the diagnosis of
      endometrial pathologies. However, the diagnosis should be confirmed by frozen
      section in patients with post-menopausal endometrial polyps and complex atypia
      hyperplasia.

PMID- 24289637
TI  - Association between p53 Arg72Pro polymorphism and the risk of human
      papillomavirus-related head and neck squamous cell carcinoma: a meta-analysis.
AB  - This study aimed to investigate the association between p53 Arg72Pro polymorphism
      and the risk of human papillomavirus (HPV)-related head and neck squamous cell
      carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched
      for relevant studies until May 30, 2013. Relevant studies were selected and data
      were extracted by two independent authors. Overall, subgroup, and sensitivity
      analyses were then conducted using the Comprehensive Meta- Analysis v2.2
      software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) =
      1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis
      results indicated no association between p53 Arg72Pro polymorphism and the risk
      of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval
      (CI) = 0.70-1.98; for Arg/Pro vs. Arg/ Arg, OR = 1.25, 95% CI = 0.97-1.72; and
      for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta
      analysis results were supported by subgroup and sensitivity analysis results. In
      conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection
      related HNSCC rather than a susceptibility gene polymorphism. 

PMID- 24289638
TI  - Determination of HER2 gene amplification in breast cancer using dual-color silver
      enhanced in situ hybridization (dc- SISH) and comparison with fluorescence ISH
      (FISH).
AB  - BACKGROUND: The two basic methods that are currently accepted to identify the
      HER2 status are immunohistochemistry and flyorescence in situ hybridization
      (FISH) . The aim of this study was to perform the dual-color silver in situ
      hybridization (dc-SISH) technique as an alternative to FISH. MATERIALS AND
      METHODS: A total of 40 invasive breast carcinoma cases were assessed for HER2
      gene amplification by FISH and dual- color SISH. RESULTS: Significant correlation
      was found in the HER2 expression results obtained with the two approaches
      (p=0.001, p<0.05). The concordance rate was 92.3%. CONCLUSIONS: Foutine practical
      use of the dc-SISH method, which is much easier to apply, score, and evaluate,
      has many advantages. HER2 and CEN17 status can be evaluated simultaneously with
      the newly developed "Dual-Color Probe". All these specifications and the reliable
      results obtained support the widespread use of SISH technique in clinical
      practice.

PMID- 24289639
TI  - Establishment of paclitaxel-resistant breast cancer cell line and nude mice
      models, and underlying multidrug resistance mechanisms in vitro and in vivo.
AB  - BACKGROUND: Breast cancer is a common malignant tumor which affects health of
      women and multidrug resistance (MDR) is one of the main factors leading to
      failure of chemotherapy. This study was conducted to establish paclitaxel
      resistant breast cancer cell line and nude mice models to explore underlying
      mechanisms of MDR. METHODS: The breast cancer drug-sensitive cell line MCF-7 (MCF
      7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant
      cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by
      MTT assay. Changes of cell morphology and ultrastructure were examined by optical
      and electron microscopy. The cell cycle distribution was determined by flow
      cytometry. Furthermore, expression of proteins related to breast cancer
      occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were
      injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were
      observed after paclitaxel treatment. In addition, proteins involved breast cancer
      and MDR were detected by immunohistochemistry. RESULTS: Compared to MCF-7/S, MCF
      7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged
      doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure.
      Estrogen receptor (ER) expression was low in drug resistant cells and tumors
      while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was
      up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and
      glutathione-S-transferase-pi (GST-pi) involved in the MDR phenotype of resistant
      cells and tumors were all overexpressed. CONCLUSION: The underlying MDR mechanism
      of breast cancer may involve increased expression of P-gp, LRP and GST-pi.

PMID- 24289640
TI  - Dental practitioners self reported performance of tobacco cessation counseling
      interventions: a cross sectional study.
AB  - BACKGROUND: The objective of the study was to determine the knowledge, attitude
      and behaviors of the practicing dentists regarding tobacco cessation counseling
      (TCC) in Chhattisgarh state and also the barriers that prevent them from doing
      so. MATERIALS AND METHODS: The study was conducted among dental practitioners of
      Raipur district, Chhattisgarh state (India). The sampling frame was registration
      with the State Dental Council and practicing in Raipur district. A questionnaire
      was personally administered and the practitioners were given explanations
      regarding how to complete it. Only descriptive statistics were calculated (SPSS
      version 16 for Windows). RESULTS: Based on the responding dentists' self reports,
      76% were not confident in TCC, 48% did not assume TCC to be their responsibility,
      17% considered that it might have a negative impact on their clinical practice,
      whereas 24% considered it might take away precious time from their practice, 25%
      considered TCC by dentists to be effective to a considerable extent and 80%
      considered TCC activities are not effective due to lack of formal training, 69%
      considered dental clinics as an appropriate place for TCC but 82% thought there
      must be separate TCC centre and 100% of the dentists wanted TCC training to be a
      part of practice and that it should be included in dental curriculum. Some 95% of
      them were of the view that tobacco products should be banned in India and 86%
      responded that health professionals must refrain from tobacco habits so to act as
      role models for society. CONCLUSIONS: Dental professionals must expand their
      armamentarium to include TCC strategies in their clinical practice. The dental
      institutions should include TCC in the curriculum and the dental professionals at
      the primary and the community health care level should also be trained in TCC to
      treat tobacco dependence.

PMID- 24289641
TI  - Geometric optimization of a mathematical model of radiofrequency ablation in
      hepatic carcinoma.
AB  - Radio frequency ablation (RFA) is an effective means of achieving local control
      of liver cancer. It is a particularly suitable mode of therapy for small and
      favorably located tumors. However, local progression rates are substantially
      higher for large tumors (>3.0 cm). In the current study, we report on a
      mathematical model based on geometric optimization to treat large liver tumors. A
      database of mathematical models relevant to the configuration of liver cancer was
      also established. The specific placement of electrodes and the frequency of
      ablation were also optimized. In addition, three types of liver cancer lesion
      were simulated by computer guidance incorporating mathematical models. This
      approach can be expected to provide a more effective and rationale mechanism for
      employing RFA in the therapy of hepatic carcinoma. 

PMID- 24289642
TI  - Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol
      on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene.
AB  - BACKGROUND: Phytochemical compounds are emerging as a new generation of
      anticancer agents with limited toxicity in cancer patients. The purpose of this
      study was to investigate the potential effcts of thymoquinone, caffeic acid
      phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress
      parameters, mRNA expression levels of proteins and survival of lung cancer cells
      in Vitro. MATERIALS AND METHODS: The A549 cell line was treated with
      benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE),
      benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ).
      Inflammatory markers, oxidative stress parameters, mRNA expression levels of
      apoptotic and anti-apoptotic proteins and cell viability were assessed and
      results were compared among study groups. RESULTS: TQ treatment up-regulated Bax
      and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ
      also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl
      2. All three agents decreased the expression of cyclin D and increased the
      expression of p21. However, the most significant up-regulation of p21 expression
      was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1
      and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and
      IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly
      decreased when compared with the control group (p=0.004). CONCLUSIONS: Our
      results revealed up-regulation of the key upstream signaling factors, which
      ultimately cause increase in their regulatory p53 levels affecting the induction
      of G2/M cell cycle arrest and apoptosis. Overall these results provide
      mechanistic insights for understanding the molecular basis and utility of the
      anti-tumor activity of TQ, RES and CAPE.

PMID- 24289643
TI  - CCNG2 suppressor biological effects on thyroid cancer cell through promotion of
      CDK2 degradation.
AB  - This study aimed to analyze the expression and clinical significance of cyclin G2
      (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression
      in a cell line. Immunohistochemistry and Western blotting were used to analyze
      CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to
      allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and
      empty vectors were transfected into the thyroid cancer K1 cell line. Reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting were
      applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle
      were also conducted to assess the influence of up-regulated expression of CCNG2
      on K1 cell biology. The level of CCNG2 protein expression was found to be
      significantly lower in thyroid cancer tissue than normal tissues (P<0.05).
      Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was
      respectively found to be significantly lower than in normal tissues (P<0.05),
      correlating with lymph node metastasis, clinic stage and histological grade
      (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression
      correlated significantly with poor overall survival time on Kaplan-Meier analysis
      (P<0.05). The results for biological functions showed that K1 cell transfected
      CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases,
      and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1
      cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid
      cancer and correlated significantly lymph node metastasis, clinic stage,
      histological grade and poor overall survival, suggesting that CCNG2 may play
      important roles as a negative regulator in thyroid cancer K1 cells by promoting
      degradation of CDK2. 

PMID- 24289644
TI  - Knowledge and attitudes toward palliative terminal cancer care among Thai
      generalists.
AB  - BACKGROUND: Our objective was to determine the knowledge and attitudes of Thai
      generalists (general physicians) toward palliative terminal cancer care (PC) in a
      primary care setting. MATERIALS AND METHODS: We performed a cross-sectional
      descriptive survey using a self-administered questionnaire. The total number of
      completed and returned questionnaires was 63, giving a 56% response rate. Data
      analysis was based on these (Cronbach's alpha=0.82) and percentages and mean
      values were assessed using the Fisher's exact test to determine the correlation
      of variables. RESULTS: Overall, attitude and knowledge levels were slightly
      satisfactory. Results indicated that general physicians had moderate scores in
      both attitudes (84.1%) and knowledge (55.7%) regarding palliative terminal cancer
      care. However, they had insufficient knowledge regarding truth telling, pain
      control and management with morphine, emergency management in terminal cancer
      care and treatment of fluid intake in terminal stages. Attitude and knowledge
      scores were statistically correlated (p=0.036). Knowledge scores were further
      positively associated with being taught palliative care in their medical
      curriculum (p=0.042). CONCLUSIONS: Formal education in palliative care and
      development of palliative care services are very much needed in Thailand to
      provide holistic care to terminally ill patients.

PMID- 24289645
TI  - Profile of lung cancer in kuwait.
AB  - BACKGROUND: Lung cancer is the most frequent cancer in males and the fourth most
      frequent site in females, worldwide. This study is the first to explore the
      profile of lung cancer in Kuwait. MATERIALS AND METHODS: Cases of primary lung
      cancer (Kuwaiti) in Kuwait cancer Registry (KCR) were grouped in 4 periods (10
      years each) from 1970-2009. Epidemiological measures; age standardized incidence
      rate (ASIR) with 95% confidence intervals (CI), Standardized rate ratio (SRR) and
      Cumulative risk and Forecasting to year 2020-2029 used for analysis. RESULTS:
      Between years, 2000-2009 lung cancer ranked the 4th and the 9th most frequent
      cancer in males and females respectively. M:F ratio 1:3. Mean age at diagnosis
      (95%CI) was 65.2 (63.9-66.4) years. The estimated risk of developing lung cancer
      before the age of 75 years in males is 1.8% (1/56), and 0.6 (1/167) in females.
      The ASIR for male cases was 11.7, 17.1, 17.0, 14.0 cases/100,000 population in
      the seventies, eighties, nineties and in 2000-2009 respectively. Female ASIR was
      2.3, 8.4, 5.1, 4.4 cases/100,000 population in the same duration. Lung cancer is
      the leading cause cancer death in males 168 (14.2%) and the fifth cause of death
      due to cancer in females accounting for 6.1% of all cancer deaths. The ASMR
      (95%CI) was 8.1 (6.6-10.0) deaths/100,000 population and 2.8 (1.3-4.3)
      deaths/100,000 population in males and females respectively. The estimated
      Mortality to incidence Ratio was 0.6. CONCLUSIONS: The incidence of lung cancer
      between years 2000-2009 is not different from that reported in the seventies. KCR
      is expecting the number of lung cancer cases to increase.

PMID- 24289646
TI  - Homogeneity in case/control numbers and north Indian caste criteria in cervical
      cancer/female urology genetic- studies at a premier medical research institute in
      lucknow, India.
AB  - Cervical cancer has emerged as a major public health problem in Lucknow and New
      York in the 21st century. Cancer genetic studies are essential to
      identify/stratify disease-susceptible individuals in a population-based cohort.
      Sample size homogeneity and North Indian caste in female urology genetic-studies
      are significant issues in meaningful interpretation of data. A review of
      scientific literature using Pubmed database was conducted, including an
      assessment of cervical cancer genetic studies conducted as part of the author's
      doctoral dissertation at a premier Lucknow-based medical research Institute.
      Sample size numbers and caste criteria in the North Indian cohort (N<=400
      subjects) were evaluated with homogeneity in the sample cohort data set(s).
      Subgroup caste-stratification of North Indian cohort is equally essential, for
      instance, Brahmin (e.g. Pandey), Vaishya (e.g. Mittal), Rajput (e.g. Singh) and
      Kshudra (e.g. Yadav) during the conception and design of genetics-based studies.
      Sample size homogeneity in histopathologically confirmed case and control numbers
      and caste-based stratification in a North Indian cohort is essential in single
      nucleotide polymorphism (SNP) studies in cervical cancer susceptible populations
      to draw more definitive conclusions. 

PMID- 24289647
TI  - Challenges to promoting population-based cancer registration in Iran: a workshop
      report.
AB  - In December 2011, the Cancer Research Centre of the Cancer Institute of Iran
      sponsored a 3-day workshop on "Cancer Registration Principle and Challenges in
      Iran", which convened cancer registry experts. The objectives of the workshop
      were: to introduce standard cancer registration, to review the policy and
      procedure of cancer registration in Iran, and to review the best practices in the
      cancer registries in Iran. Challenges to cancer registration were discussed and
      recommendations were developed. The workshop was evaluated by participants for
      better organization of subsequent workshops. The objective of publication of this
      report is that based on Cancer in 5 Continents, many low- or middle-income
      countries do not meet the criteria for a standard population-based cancer
      registry (PBCR); on the other hand cancer is the most important cause of
      mortality and the essential part of any cancer control program is the cancer
      registry. Therefore this report focuses on problems and challenges of PBCR and
      provides recommendations which might help other developing countries to decrease
      their PBCR defects. 

PMID- 24289648
TI  - Poverty does not limit tobacco consumption among tribal populations: evidence
      from Central India.

PMID- 24289649
TI  - Risk factors for musculoskeletal pain amongst nurses in Estonia: a cross
      sectional study.
AB  - BACKGROUND: Routine statistics indicate a high frequency of work-related
      musculoskeletal disorders in Estonia. We aimed to describe the prevalence of
      musculoskeletal pain (MSP) amongst Estonian nurses, and to explore associations
      with personal characteristics and occupational risk factors. METHODS: As a part
      of an international investigation (the Cultural and Psychosocial Influences on
      Disability (CUPID) study), a cross-sectional survey was carried out amongst
      registered nurses at Tartu University Hospital, focusing on pain at six
      anatomical sites (low back, neck, shoulder, elbow, wrist/hand and knee) lasting
      for more than a day during the past year and past month. Associations with
      regional and multi-site (>=2 anatomical sites) pain were analysed by logistic
      regression. RESULTS: Analysis was based on 221 female nurses (response rate 57%).
      The overall prevalence of MSP was 84% in the past year and 69% in the past month.
      The prevalence of multi-site pain was 60% in the past year and 40% in the past
      month. Low back, neck and knee were the sites most commonly painful. Pain in the
      past year tended to be more frequent at older ages, and with higher emotional
      exhaustion, and at most sites, with poor self-rated health, and reported distress
      from somatic symptoms. Multi-site pain was also significantly associated with
      older age and tendency to somatise. CONCLUSIONS: The prevalence of MSP among
      Estonian nurses is high. Psychological risk factors such as somatising tendency
      have an important impact. However, none of the risk factors examined seems likely
      to explain the high frequency of work-related musculoskeletal disorders in
      Estonia.

PMID- 24289650
TI  - Double-duty caregivers: healthcare professionals juggling employment and informal
      caregiving. A survey on personal health and work experiences.
AB  - AIMS: This study compared the work-related experiences and personal health status
      of double-duty caregivers with those of caregivers who do not provide informal
      care to a family member or close friend in need. BACKGROUND: The interest in
      providing informal care alongside employment is growing. However, little
      attention has been paid to the dual role of the healthcare professional who also
      has caregiving responsibilities for a needy person in his/her private situation.
      It is important to study the negative and positive consequences of this
      combination of professional and family care giving. DESIGN: A cross-sectional
      study. METHODS: In 2011, we distributed a digital questionnaire to employees with
      a professional care function working at a healthcare organization in the
      Netherlands. Descriptive statistics, analyses of covariance and tests of
      linearity were performed. RESULTS: Analyses of variance demonstrated that as
      professional healthcare workers provide more hours of informal care in their
      private lives, their mental and physical health significantly worsens, while
      their need for recovery increases. Also, statistical significant increases were
      seen for emotional exhaustion, presenteeism and negative experiences with Work
      Home and Home-Work Interferences. Remarkably, positive Home-Work Interference
      increased significantly with increasing hours of informal care. Double-duty
      caregivers appeared to be equally motivated and satisfied with their work as
      their co-workers. No differences were seen with respect to absenteeism.
      CONCLUSION: Double-duty caregivers prove to be employees who are at risk of
      developing symptoms of overload. This finding calls for special attention, with
      long-term solutions at both legislative and organizational level.

PMID- 24289651
TI  - Incarceration is associated with used syringe lending among active injection drug
      users with detectable plasma HIV-1 RNA: a longitudinal analysis.
AB  - BACKGROUND: Informed by recent studies demonstrating the central role of plasma
      HIV-1 RNA viral load (VL) on HIV transmission, interventions to employ HIV
      antiretroviral treatment as prevention (TasP) are underway. To optimize these
      efforts, evidence is needed to identify factors associated with both non
      suppressed VL and HIV risk behaviours. Thus, we sought to assess the possible
      role played by exposure to correctional facilities on VL non-suppression and used
      syringe lending among HIV-seropositive people who use injection drugs (PWID).
      METHODS: We used data from the ACCESS study, a community-recruited prospective
      cohort. We used longitudinal multivariate mixed-effects analyses to estimate the
      relationship between incarceration and plasma HIV-1 RNA > 500 copies/mL among
      antiretroviral therapy (ART)-exposed active PWID and, during periods of non
      suppression, the relationship between incarceration and used syringe lending.
      RESULTS: Between May 1996 and March 2012, 657 ART-exposed PWID were recruited.
      Incarceration was independently associated with higher odds of VL non-suppression
      (Adjusted Odds Ratio [AOR] = 1.54, 95% Confidence Interval [95% CI]: 1.10, 2.16).
      In a separate multivariate model restricted to periods of VL non-suppression,
      incarceration was independently associated with lending used syringes (AOR =
      1.81, 95% CI: 1.03, 3.18). CONCLUSIONS: The current findings demonstrate that
      incarceration is associated with used syringe lending among active PWID with
      detectable plasma HIV-1 RNA. Our results provide a possible pathway for the
      commonly observed association between incarceration and increased risk of HIV
      transmission. Our results suggest that alternatives to incarceration of non
      violent PWID and evidence-based combination HIV prevention interventions for PWID
      within correctional facilities are urgently needed.

PMID- 24289652
TI  - Diagnosis and treatment of solid pseudopapillary tumor of the pancreas:
      experience of one single institution from Turkey.
AB  - BACKGROUND: Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely
      rare epithelial tumor of low malignant potential. SPN accounts for less than 1%
      to 2% of exocrine pancreatic tumors. The aim of this study is to report our
      experience with SPN of the pancreas. It includes a summary of the current
      literature to provide a reference for the management of this rare clinical
      entity. METHODS: A retrospective analysis was performed of all patients diagnosed
      and treated for SPN in our hospital over the past 15 years (1998 to 2013). A
      database of the characteristics of these patients was developed, including age,
      gender, tumor location and size, treatment, and histopathological and
      immunohistochemical features. RESULTS: During this time period, 255 patients with
      pancreatic malignancy (which does not include ampulla vateri, distal choledocal
      and duodenal tumor) were admitted to our department, only 10 of whom were
      diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient
      was a man (10%). Their median age was 38.8 years (range 18 to 71). The most
      common symptoms were abdominal pain and dullness. Seven patients (70%) presented
      with abdominal pain or abdominal dullness and three patient (30%) were
      asymptomatic with the diagnosis made by an incidental finding on routine
      examination. Abdominal computed tomography and/or magnetic resonance imaging
      showed the typical features of solid pseudopapillary neoplasm in six (60%) of the
      patients. Four patients underwent distal pancreatectomy with splenectomy, one
      patient underwent a total mass excision, and one patient underwent total
      pancreatic resection. Two required extended distal pancreatectomy with
      splenectomy. Two underwent spleen-preserving distal pancreatectomy. CONCLUSIONS:
      SPN is a rare neoplasm that primarily affects young women. The prognosis is
      favorable even in the presence of distant metastasis. Although surgical resection
      is generally curative, a close follow-up is advised in order to diagnose a local
      recurrence or distant metastasis and choose the proper therapeutic option for the
      patient.

PMID- 24289653
TI  - Laminoplasty versus laminectomy for multi-level cervical spondylotic myelopathy:
      a systematic review of the literature.
AB  - BACKGROUND: There is considerable controversy as to which posterior technique is
      best for the treatment of multi-level cervical spondylotic myelopathy. The aim of
      this study was to compare the clinical and radiographic results and complications
      of laminoplasty (LAMP) and laminectomy (LAMT) in the treatment of multi-level
      cervical spondylotic myelopathy. METHODS: We reviewed and analyzed papers
      published from January 1966 and June 2013 regarding the comparison of LAMP and
      LAMT for multi-level cervical spondylotic myelopathy. Statistical comparisons
      were made when appropriate. RESULTS: Fifteen studies were included in this
      systematic review. There was no significant difference in the incidence of
      surgical complications between LAMP and LAMT. Compared to conventional LAMT and
      skip LAMT, postoperative ROM was more limited in LAMP, but this was still
      superior to postoperative ROM following LAMT with fusion. Postoperative kyphosis
      occurred in 8/180 (4.44%) in LAMP and 13/205 (6.34%) in LAMT, whereas no cases of
      kyphosis were reported for skip LAMT. Skip LAMT appears to have better clinical
      outcomes than LAMP, while the outcome was similar between LAMP and LAMT with
      fusion. CONCLUSIONS: Based on these results, a claim of superiority for
      laminoplasty or laminectomy was not justified. In deciding between the two
      procedures, the risks of surgical and neurological complications, and radiologic
      and clinical outcome, must be taken into consideration if both options are
      available in multi-level cervical spondylotic myelopathy.

PMID- 24289654
TI  - Clinical experience with modified Miccoli's endoscopic thyroidectomy for
      treatment of thyroid carcinoma in 86 cases.
AB  - BACKGROUND: The main purpose of this study was to assess the feasibility and
      relevant applying techniques of total thyroidectomy for thyroid carcinoma with a
      modified Miccoli's approach. METHODS: Eighty-six patients with thyroid carcinoma
      consecutively received radical operation from October 2007 to June 2012. A cavity
      above the gland was constructed by a modified suspension method using the
      suspension retractor with suction catheter after the pathway making. Eighty-six
      cases underwent the modified Miccoli's endoscopic thyroidectomy using the
      ultrasonic scalpel and the space maintain-regulating device. Level VI lymph node
      dissection was performed using the method of inspection pit. RESULTS: All the
      procedures were completed successfully. The average detection rate of level VI
      lymph nodes, the average time of thyroidectomy and lymph nodes dissection were
      7.27 +/- 3.99 pieces per case, 51.32 +/- 13.35 min, and 38.43 +/- 15.24 min,
      respectively. With regard to postoperative complications, there were three cases
      of delayed transient hoarseness, two patients with transient numbness of hands
      and feet, one subject with chylous fistula, and no hemorrhage. CONCLUSION: Total
      thyroidectomy for thyroid carcinoma can be safely performed with the modified
      Miccoli's approach by using ultrasonic scalpel and the space maintain-regulating
      device. Application of these adaptive reforms can obviously reduce the
      difficulties in manipulation and have the advantages of minimal incisions, good
      cosmetic results, less bleeding, shorter hospital stay, and fewer complications.

PMID- 24289655
TI  - Clinical pharmacology review of escitalopram for the treatment of depression.
AB  - INTRODUCTION: Depression is a serious and debilitating psychiatric condition with
      serious societal health and economic implications. Escitalopram , the S
      enantiomer of racemic citalopram, is an effective treatment for major depressive
      disorder. AREAS COVERED: This review covers the clinical pharmacology of
      escitalopram, with emphasis on regulatory approval. Its pharmacokinetics,
      pharmacodynamics and clinical efficacy for major depressive disorder are
      evaluated, along with data regarding safety and tolerability. EXPERT OPINION:
      Drug development of escitalopram was heavily guided by prior approval of
      citalopram. Select safety and efficacy studies for escitalopram in combination
      with supportive evidence from the results of prior citalopram studies allowed for
      regulatory approval for acute and maintenance claims in both adults and
      adolescents, while minimizing burden on the sponsor. Escitalopram has been shown
      to have better efficacy and safety profile than other selective serotonin
      reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs,
      including racemic citalopram. The first generic escitalopram was approved in
      2012, along with Abbreviated New Drug Applications. The associated cost savings
      have helped reduce the burden of weighing the benefits of escitalopram over less
      expensive alternatives.

PMID- 24289656
TI  - Ultra low concentration deltamethrin loaded patch development and evaluation of
      its repellency against dengue vector Aedes (S) albopictus.
AB  - BACKGROUND: Mosquito repellents and emanators confer protection against mosquito
      bites through spatial action of emanated vapours which are released into the
      adjoining environment. Synthetic insecticides released into the environment in
      ultra low volume vapour phase deter the mosquitoes from biting humans in a
      protected space. METHODS: Formulation patches were prepared using the solvent
      evaporation method over a backing membrane and using Dibutylphthalate (DBT) as a
      plasticizer. The effect of formulation variables on the deltamethrin release from
      the patch matrices were studied under accelerated conditions, whereas, HPLC was
      used for quantitative estimation of deltamethrin. The prepared patch formulations
      were subjected to physicochemical studies, such as, deltamethrin content,
      thickness, weight variation, percent moisture content, moisture uptake, surface
      area and surface pH determination. Deltamethrin-polymer interaction and
      compatibility was ascertained using DSC and FT-IR, while surface morphology and
      deltamethrin distribution in the patch were studied using SEM technique.
      Repellent activity of the patch formulations was evaluated against Ae. albopictus
      mosquitoes. RESULTS: Blends of polymeric combinations of polyvinylpyrrolidone
      (PVP) and ethyl-cellulose (EC) with admixture of deltamethrin provided prolonged
      repellent activity against Ae. albopictus mosquitoes. Physicochemical
      characterisation indicated the suitability of deltamethrin patch formulation with
      the polymeric combinations of PVP and EC. Patches were very effective against
      laboratory reared Ae. albopictus mosquitoes. No significant difference was
      observed between the performance of test patches and commercially available
      repellent cream Mosqshield(r). CONCLUSION: Deltamethrin loaded patches provided
      effective repellency against Ae. albopictus mosquitoes. The study emphasised that
      deltamethrin released to the environment in low concentration could be an
      excellent spatial repellent against hematophagous mosquitoes.

PMID- 24289657
TI  - Internet information on xerostomia: what should patients expect?
AB  - OBJECTIVE: To assess the qualitative standards of the information distributed via
      the Internet regarding xerostomia. MATERIALS AND METHODS: A comprehensive
      electronic search was performed for 'xerostomia' and 'dry mouth' separately using
      four search engines. The first 30 results from each search term-engine
      combination were pooled for analysis. After excluding promotional product sites,
      discussion groups, video feeds, scientific articles, non-operative sources, sites
      with denied direct access through password requirement, non-English language
      domains, and online medical dictionaries, 50 Web pages were evaluated in terms of
      readability, accessibility, usability, and reliability using recommended research
      methodology the Flesch Reading Ease Score and the LIDA instrument. Author and
      information details were also recorded. RESULTS: The results revealed a variable
      quality of the available Internet information on xerostomia. The Web sites
      required advanced reading skills, while LIDA scores for accessibility, usability,
      and reliability ranged from medium to low with average scores extending from
      29.1% to 81.3%. CONCLUSIONS: The quality of information about xerostomia among
      Web sources presents high variability. The existing discrepancy should be
      alleviated by referring patients to evidence-based education materials on the
      Internet. Improvement in xerostomia information e-resources will contribute to a
      more advanced quality in oral health care.

PMID- 24289658
TI  - Antibody persistence 1 year after pandemic H1N1 2009 influenza vaccination and
      immunogenicity of subsequent seasonal influenza vaccine among adult organ
      transplant patients.
AB  - We investigated the antibody persistence in solid organ transplant (SOT)
      recipients 1 year after immunization with two doses of monovalent AS03-adjuvanted
      influenza A(H1N1)pdm09 vaccine. We also assessed the boosting effect of the
      seasonal trivalent inactivated vaccine 2010 (TIV/10) that contained the influenza
      A(H1N1)pdm09 strain. A total of 49 SOT recipients and 11 healthy controls were
      included. After a blood sample was obtained to assess the persistent immunity,
      one dose of TIV/10 was administered and another blood sample was collected 1
      month after vaccination. A(H1N1)pdm09 antibodies were measured using a
      haemagglutination inhibition assay. The percentage of SOT recipients with
      protective titres decreased between 1 month and 10-14 months after the monovalent
      influenza A(H1N1)pdm09 vaccination, from 79% (n = 38) to 47% (n = 23) (P = 0.02).
      The corresponding numbers for the control group were 100% and 63%, respectively
      (P = 0.008). After the TIV/10 boosting dose, the number of SOT recipients with
      protective titres increased from 47% (n = 23) to 71% (n = 35) (P = 0.2). All the
      controls reached a protective titre level. The median titre rise was
      significantly higher among controls when compared to SOT recipients (P = 0.0036).
      No rejection or adverse events were seen. The results show an obvious need for
      vaccine boosting doses in the SOT patients.

PMID- 24289659
TI  - Developmental trajectories of schizotypal personality disorder-like behavioural
      manifestations: a two-year longitudinal prospective study of college students.
AB  - BACKGROUND: Previous evidence has shown that schizotypal personality disorder
      (SPD) is part of the schizophrenia spectrum. Few studies have examined latent
      classes in the developmental trajectories of SPD features over time in
      individuals with SPD features. METHODS: We adopted a longitudinal prospective
      study design to follow up a cohort of 660 college students during a two-year
      period. Participants' SPD-like symptoms and psychosocial function were measured
      by a comprehensive set of questionnaires that covered SPD features and cognitive,
      emotional, and psychosocial functions. Latent class growth analysis was used to
      examine the trajectory classes. RESULTS: Three trajectory classes were
      identified: a low, a medium, and a high SPD features group. Participants in the
      low group reported few SPD features and their symptoms declined over time. The
      medium group students had more SPD features than the low group and these symptoms
      stabilized during the follow up period. Participants in the high group reported
      the most SPD features and their symptoms increased over time. The three groups
      differed in paranoid thoughts, psychological distress, neurocognition function,
      and emotional expression over time. Results of multivariate regression analysis
      suggested that paranoid thoughts, emotional experience and prospective memory
      were predictors of social functioning in the high SPD feature group. CONCLUSIONS:
      Our findings suggest that individuals with SPD features may be delineated into
      different developmental subgroups and these subgroups differ significantly in
      psychosocial function. Delusions, emotion, and prospective memory may be
      important features to consider in early diagnosis and interventions for
      individuals predisposed to SPD and schizophrenia.

PMID- 24289661
TI  - Development of a sensitive and specific qPCR assay in conjunction with propidium
      monoazide for enhanced detection of live Salmonella spp. in food.
AB  - BACKGROUND: Although a variety of methodologies are available for detection of
      Salmonella, sensitive, specific, and efficient methods are urgently needed for
      differentiation of live Salmonella cells from dead cells in food and
      environmental samples. Propidium monoazide (PMA) can preferentially penetrate the
      compromised membranes of dead cells and inhibit their DNA amplification, however,
      such inhibition has been reported to be incomplete by some studies. In the
      present study, we report an efficient qPCR assay targeting a conserved region of
      the invA gene of Salmonella in conjunction with PMA treatment for detection of
      DNA from live Salmonella cells in food samples. RESULTS: We investigated the
      relationship between amplicon length and inhibitory effect of PMA treatment to
      prevent DNA amplification from dead cells while allowing for DNA amplification
      from live cells, and found that the two factors are well correlated with each
      other. An amplicon that is 130 bp in length was determined to be optimal for PMA
      treatment and was selected for further PMA-qPCR assay development. A PMA-qPCR
      assay was established by utilizing this amplicon and adopting a modified PMA
      treatment procedure. The PMA-qPCR assay provided excellent inhibition of DNA
      amplification from dead cells (a 17-CT-value, or 128,000-fold reduction) while
      only a slight DNA amplification difference (0.5 CT value) was noted between the
      PMA-treated and untreated live cells. This assay has been validated through
      stringent inclusivity and exclusivity studies using a large number of (n = 167)
      Salmonella, including all strains of SARA and SARB collections, and non
      Salmonella strains (n = 36). This PMA-qPCR assay is capable of detecting live
      Salmonella cells in live/dead cell mixtures, or 30 CFU/g live Salmonella cells
      from enriched spiked spinach samples as early as 4 h. CONCLUSIONS: A 130-bp
      amplicon in invA gene was demonstrated to be optimal for PMA treatment for
      selective detection of live Salmonella cells by PCR. This PMA-qPCR assay provides
      a sensitive, specific, and efficient method for detecting live Salmonella cells
      in foods and environmental samples and may have an impact on the accurate
      microbiological monitoring of Salmonella in foods and environment samples.

PMID- 24289662
TI  - Factors promoting a successful return to work: from an employer and employee
      perspective.
AB  - OBJECTIVE: Efforts have been made to explain the inability to return to work
      (RTW) due to employees' chronic musculoskeletal pain. Knowledge of factors
      facilitating the RTW process is however still limited. Based on the experiences
      of employees and employers, this study aims to identify factors promoting a
      successful return process for persons with chronic musculoskeletal pain. METHODS:
      The findings from interviews, involving six employees with musculoskeletal pain,
      and five employers with various work experience, were analysed by Giorgi's
      phenomenological analysis through four stages. RESULTS: The major themes
      underlying the employees' comments for a successful RTW were identifying and
      mobilizing their personal resources, adapting a balanced daily life, and
      requiring a positive dialogue with family and their employer, while the employers
      underlined the need for a helpful adjustment at work and how they wanted to
      become more involved in the rehabilitation process. CONCLUSIONS: In conclusion
      our findings underline the need for extended collaboration between the employees,
      employer, and rehabilitation staff, and should encourage occupational therapists
      to direct even more of their expertise towards the situation at the workplace.

PMID- 24289660
TI  - Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV
      associated neuroinflammation?
AB  - Human immunodeficiency virus type 1 (HIV) continues to be one of the most
      prevalent global health afflictions to date. The advent and introduction of
      combined antiretroviral therapy (cART) has made a significant impact on the
      course of infection. However, as patients are living longer, many HIV-associated
      illnesses are becoming prevalent among the infected population, especially those
      associated with chronic inflammation. Consistently, HIV-associated
      neuroinflammation is believed to be a major catalyst in the development of HIV
      associated neurocognitive disorders (HAND), which are estimated to persist in
      approximately 50% of infected individuals regardless of cART. This dramatically
      underscores the need to develop effective adjunctive therapies capable of
      controlling this aspect of the disease, which are currently lacking.We previously
      demonstrated that the inflammatory mediator soluble CD40 ligand (sCD40L) is
      elevated in both the plasma and cerebrospinal fluid of cognitively impaired
      infected individuals compared to their non-impaired infected counterparts. Our
      group, and others have recently demonstrated that there is an increasing role for
      this inflammatory mediator in the pathogenesis of HIV-associated
      neuroinflammation, thereby identifying this molecule as a potential therapeutic
      target for the management of HAND. Platelets are the major source of circulating
      sCD40L, and these small cells are increasingly implicated in a multitude of
      inflammatory disorders, including those common during HIV infection. Thus,
      antiplatelet therapies that minimize the release of platelet-derived inflammatory
      mediators such as sCD40L are an innovative, non-traditional approach for the
      treatment of HIV-associated neuroinflammation, with the potential to benefit
      other HIV-associated illnesses. 

PMID- 24289663
TI  - Silica-associated connective tissue syndrome with acquired hemophilia (Factor
      VIII inhibitor), presenting with life-threatening bleed.

PMID- 24289664
TI  - TpBGL2 codes for a Tetrapisispora phaffii killer toxin active against wine
      spoilage yeasts.
AB  - Tetrapisispora phaffii produces a killer toxin known as Kpkt that has extensive
      anti-Hanseniaspora/Kloeckera activity under winemaking conditions. Kpkt has a
      beta-glucanase activity and induces ultrastructural modifications in the cell
      wall of sensitive strains, with a higher specific cytocidal activity and a
      selective action towards target yeast cells. In this study, a two-step PCR-based
      approach was used to isolate the gene coding beta-glucanase of T. phaffii.
      Initially, a fragment of the open reading frame was isolated by degenerate PCR,
      with primers designed on the NH2 -terminal sequence of the protein and on
      conserved motifs of Bgl2p of Saccharomyces cerevisiae and Candida albicans.
      Subsequently, the entire sequence of the gene was obtained by inverse PCR. blast
      analyses of TpBGL2 highlight high identity with homologous genes in other yeast
      species, in which TpBGL2p shows no killer activity. However, gene disruption
      resulted in complete loss of the glucanase activity and the killer phenotype,
      thus confirming that TpBgl2p has a killer activity. 

PMID- 24289665
TI  - Development of a cost effective three-dimensional posture analysis tool: validity
      and reliability.
AB  - BACKGROUND: The lack of clear understanding of the association between sitting
      posture and adolescent musculoskeletal pain, might reflect invalid and/or
      unreliable posture measurement instruments. The psychometric properties of any
      new measurement instrument should be demonstrated prior to use for research or
      clinical purposes. This paper describes psychometric testing of a new three
      dimensional (3D), portable, non-invasive posture analysis tool (3D-PAT), from
      sequential studies using a mannequin and high school students. METHODS: The first
      study compared the 3D-(X-, Y- and Z-) coordinates of reflective markers placed on
      a mannequin using the 3D-PAT, and the Vicon motion analysis system. This study
      also tested the reliability of taking repeated measures of the 3D-coordinates of
      the reflective markers. The second study determined the concurrent validity and
      test-retest reliability of the 3D-PAT measurements of nine sitting postural
      angles of high school students undertaking a standard computing task. In both
      studies, concordance correlation coefficients and Intraclass correlation
      coefficients described test-retest reliability, whilst Pearson product moment
      correlation coefficients and Bland-Altman plots demonstrated concurrent validity.
      RESULTS: The 3D-PAT provides reliable and valid 3D measurements of five of the
      nine postural angles i.e. head flexion, neck flexion, cranio-cervical angle,
      trunk flexion and head lateral bending in adolescents undertaking a standard
      task. CONCLUSIONS: The 3D-PAT is appropriate for research and clinical settings
      to measure five upper quadrant postural angles in three dimensions. As a
      measurement instrument it can provide further understanding of the relationship
      between sitting posture, changes to sitting posture and adolescent
      musculoskeletal pain.

PMID- 24289666
TI  - Turn-over rate of academic faculty at the College of Health Sciences, Addis Ababa
      University: a 20-year analysis (1991 to 2011).
AB  - BACKGROUND: Faculty turn-over affects both workers and organizations. Turnover of
      faculty and researchers is increasing alarmingly and costing the universities and
      the country at large. Fast turnover of health professionals from the health
      system and from academic institutions has recently received substantial attention
      from both academia and health sector managers. This paper calculates the faculty
      turnover rate at the College of Health Sciences of Addis Ababa University during
      the period of September 1991 to August 2011. METHODS: The study was conducted at
      the College of Health Sciences, Addis Ababa University. Retrospective analysis of
      employee records was done. All records of the faculty that were working in the
      College during the 20-year period, starting from September 1991 to August 2011
      were retrospectively reviewed. Data were collected from the employee records
      accessed from the College's human resources database and supplemented by payroll
      sheets and different reports. A structured checklist was used to extract the
      required data from the database. The crude turnover rate for academic faculty was
      calculated. RESULTS: Within the 20-year period of September 1991 to August 2011,
      a total of 120 faculty members left. The overall turn-over rate was 92.8 %. The
      rate in the most recent five years (172 %) is 8.5 times higher than the rate for
      the first five years (20 %). The average retention period before the termination
      of an employment contract was 4.9 years. The top five departments where
      employment contracts were relatively higher include: Nursing 15 (15.6 %),
      Internal Medicine 12 (12.5%), Public Health 10 (10.4%), Pediatrics 9 (9.4%) and
      Surgery 9 (9.4%). About two thirds (66.6%) of the faculty who were leaving were
      at the ranks of assistant professorship and above. CONCLUSION: This study
      revealed that outflow of faculty has been continuously increasing in the period
      reviewed. This implies that the College had been losing highly skilled
      professionals with considerably higher costs in monetary terms. In this regard,
      an urgent response is required to retain or significantly decrease the outflow of
      faculty. Different motivation and retention mechanisms should be identified and
      implemented. Various modalities of faculty development programs should also be
      initiated.

PMID- 24289667
TI  - Development of an educational cartoon to prevent worm infections in Chinese
      schoolchildren.
AB  - BACKGROUND: With more than two billion people infected worldwide, soil
      transmitted helminths (STH) are the most widespread infections. To date, STH
      control efforts rely predominantly on recurrent mass drug administration (MDA),
      which does not prevent reinfection. Additional public health measures including
      novel health educational tools are required for more sustained integrated control
      of STH. We describe the development of an educational cartoon video (The Magic
      Glasses) targeting STH infections in Chinese schoolchildren and its pilot testing
      in China.We applied an extensive community-based mixed methods approach involving
      input from the target group of 9-10 year old schoolchildren and key informants,
      such as teachers, doctors and parents, in order to identify potential STH
      infection risks in the study area and to formulate key messages for the cartoon.
      The development of the educational cartoon included three major steps: formative
      research, production, and pilot testing and revision. RESULTS: We found that most
      adults and approximately 50% of the schoolchildren were aware of roundworm
      (Ascaris) infection, but knowledge of transmission, prevention and treatment of
      STH was poor. Observations in the study area showed that unhygienic food
      practices, such as eating raw and unwashed fruit or playing in vegetable gardens
      previously fertilised with human faeces, posed major STH infection risks.
      CONCLUSIONS: It was crucial to assess the intellectual, emotional, social and
      cultural background of the target population prior to video production in order
      to integrate the key messages of the cartoon into everyday situations. Overall,
      our strategy for the development of the cartoon and its incorporation into a
      health education package proved successful, and we provide a summary of
      recommendations for the development of future educational videos based on our
      experiences in China.

PMID- 24289668
TI  - A data mining approach for grouping and analyzing trajectories of care using
      claim data: the example of breast cancer.
AB  - BACKGROUND: With the increasing burden of chronic diseases, analyzing and
      understanding trajectories of care is essential for efficient planning and fair
      allocation of resources. We propose an approach based on mining claim data to
      support the exploration of trajectories of care. METHODS: A clustering of
      trajectories of care for breast cancer was performed with Formal Concept
      Analysis. We exported Data from the French national casemix system, covering all
      inpatient admissions in the country. Patients admitted for breast cancer surgery
      in 2009 were selected and their trajectory of care was recomposed with all
      hospitalizations occuring within one year after surgery. The main diagnoses of
      hospitalizations were used to produce morbidity profiles. Cumulative hospital
      costs were computed for each profile. RESULTS: 57,552 patients were automatically
      grouped into 19 classes. The resulting profiles were clinically meaningful and
      economically relevant. The mean cost per trajectory was 9,600?. Severe conditions
      were generally associated with higher costs. The lowest costs (6,957?) were
      observed for patients with in situ carcinoma of the breast, the highest for
      patients hospitalized for palliative care (26,139?). CONCLUSIONS: Formal Concept
      Analysis can be applied on claim data to produce an automatic classification of
      care trajectories. This flexible approach takes advantages of routinely collected
      data and can be used to setup cost-of-illness studies.

PMID- 24289669
TI  - Optimal strategies for estimating the average fidelity of quantum gates.
AB  - We show that the minimum experimental effort to estimate the average error of a
      quantum gate scales as 2(n) for n qubits and requires classical computational
      resources ~n(2)2(3n) when no specific assumptions on the gate can be made. This
      represents a reduction by 2(n) compared to the best currently available protocol,
      Monte Carlo characterization. The reduction comes at the price of either having
      to prepare entangled input states or obtaining bounds rather than the average
      fidelity itself. It is achieved by applying Monte Carlo sampling to so-called 2
      designs or two classical fidelities. For the specific case of Clifford gates, the
      original version of Monte Carlo characterization based on the channel-state
      isomorphism remains an optimal choice. We provide a classification of the
      available efficient strategies to determine the average gate error in terms of
      the number of required experimental settings, average number of actual
      measurements, and classical computational resources.

PMID- 24289670
TI  - Beyond spectral homodyne detection: complete quantum measurement of spectral
      modes of light.
AB  - Spectral homodyne detection, a widely used technique for measuring quantum
      properties of light beams, cannot retrieve all the information needed to
      reconstruct the quantum state of spectral field modes. We show that full quantum
      state reconstruction can be achieved with the alternative measurement technique
      of resonator detection. We experimentally demonstrate this difference by
      engineering a quantum state with features that go undetected by homodyne
      detection but are clearly revealed by resonator detection. 

PMID- 24289671
TI  - Quantum self-correction in the 3D cubic code model.
AB  - A big open question in the quantum information theory concerns the feasibility of
      a self-correcting quantum memory. A quantum state recorded in such memory can be
      stored reliably for a macroscopic time without need for active error correction,
      if the memory is in contact with a cold enough thermal bath. Here we report
      analytic and numerical evidence for self-correcting behavior in the quantum spin
      lattice model known as the 3D cubic code. We prove that its memory time is at
      least L(cbeta), where L is the lattice size, beta is the inverse temperature of
      the bath, and c>0 is a constant coefficient. However, this bound applies only if
      the lattice size L does not exceed a critical value which grows exponentially
      with beta. In that sense, the model can be called a partially self-correcting
      memory. We also report a Monte Carlo simulation indicating that our analytic
      bounds on the memory time are tight up to constant coefficients. To model the
      readout step we introduce a new decoding algorithm, which can be implemented
      efficiently for any topological stabilizer code. A longer version of this work
      can be found in Bravyi and Haah, arXiv:1112.3252.

PMID- 24289672
TI  - Proton kinetic effects and turbulent energy cascade rate in the solar wind.
AB  - The first observed connection between kinetic instabilities driven by proton
      temperature anisotropy and estimated energy cascade rates in the turbulent solar
      wind is reported using measurements from the Wind spacecraft at 1 AU. We find
      enhanced cascade rates are concentrated along the boundaries of the (beta?,
      T?/T?) plane, which includes regions theoretically unstable to the mirror and
      firehose instabilities. A strong correlation is observed between the estimated
      cascade rate and kinetic effects such as temperature anisotropy and plasma
      heating, resulting in protons 5-6 times hotter and 70%-90% more anisotropic than
      under typical isotropic plasma conditions. These results offer new insights into
      kinetic processes in a turbulent regime.

PMID- 24289673
TI  - Real-time dynamics of string breaking.
AB  - We study the real-time dynamics of string breaking in quantum electrodynamics in
      one spatial dimension. A two-stage process with a clear separation of time and
      energy scales for the fermion-antifermion pair creation and subsequent charge
      separation leading to the screening of external charges is found. Going away from
      the traditional setup of external static charges, we establish the phenomenon of
      multiple string breaking by considering dynamical charges flying apart. 

PMID- 24289674
TI  - Universality of abrupt holographic quenches.
AB  - We make an analytic investigation of rapid quenches of relevant operators in d
      dimensional holographic conformal field theories, which admit a dual gravity
      description. We uncover a universal scaling behavior in the response of the
      system, which depends only on the conformal dimension of the quenched operator in
      the vicinity of the ultraviolet fixed point of the theory. Unless the amplitude
      of the quench is scaled appropriately, the work done on a system during the
      quench diverges in the limit of abrupt quenches for operators with dimension
      (d/2)<=Delta<d. 

PMID- 24289675
TI  - Higgs Boson pair production at next-to-next-to-leading order in QCD.
AB  - We compute the next-to-next-to-leading order QCD corrections for standard model
      Higgs boson pair production inclusive cross section at hadron colliders within
      the large top-mass approximation. We provide numerical results for the LHC,
      finding that the corrections are large, resulting in an increase of O(20%) with
      respect to the next-to-leading order result at c.m. energy sqrt[sH]=14  TeV. We
      observe a substantial reduction in the scale dependence, with overlap between the
      current and previous order prediction. All our results are normalized using the
      full top- and bottom-mass dependence at leading order. We also provide analytical
      expressions for the K factors as a function of sH.

PMID- 24289678
TI  - Is there a flavor hierarchy in the deconfinement transition of QCD?
AB  - We present possible indications for flavor separation during the QCD crossover
      transition based on continuum extrapolated lattice QCD calculations of higher
      order susceptibilities. We base our findings on flavor-specific quantities in the
      light and strange quark sector. We propose a possible experimental verification
      of our prediction, based on the measurement of higher order moments of identified
      particle multiplicities. Since all our calculations are performed at zero
      baryochemical potential, these results are of particular relevance for the heavy
      ion program at the LHC. 

PMID- 24289679
TI  - Braiding of atomic majorana fermions in wire networks and implementation of the
      Deutsch-Jozsa algorithm.
AB  - We propose an efficient protocol for braiding Majorana fermions realized as edge
      states in atomic wire networks, and demonstrate its robustness against
      experimentally relevant errors. The braiding of two Majorana fermions located on
      one side of two adjacent wires requires only a few local operations on this side
      which can be implemented using local site addressing available in current
      experiments with cold atoms and molecules. Based on this protocol we provide an
      experimentally feasible implementation of the Deutsch-Jozsa algorithm for two
      qubits in a topologically protected way. 

PMID- 24289680
TI  - Femtojoule-scale all-optical latching and modulation via cavity nonlinear optics.
AB  - We experimentally characterize Hopf bifurcation phenomena at femtojoule energy
      scales in a multiatom cavity quantum electrodynamical (cavity QED) system and
      demonstrate how such behaviors can be exploited in the design of all-optical
      memory and modulation devices. The data are analyzed by using a semiclassical
      model that explicitly treats heterogeneous coupling of atoms to the cavity mode.
      Our results highlight the interest of cavity QED systems for ultralow power
      photonic signal processing as well as for fundamental studies of mesoscopic
      nonlinear dynamics. 

PMID- 24289681
TI  - Time delay in the recoiling valence photoemission of ar endohedrally confined in
      C60.
AB  - The effects of confinement and electron correlations on the relative time delay
      between the 3s and 3p photoemissions of Ar confined endohedrally in C60 are
      investigated using the time-dependent local density approximation--a method that
      is also found to mostly agree with recent time delay measurements between the 3s
      and 3p subshells in atomic Ar. At energies in the neighborhood of 3p Cooper
      minimum, correlations with C60 electrons are found to induce opposite temporal
      effects in the emission of Ar 3p hybridized symmetrically versus that of Ar 3p
      hybridized antisymmetrically with C60. A recoil-type interaction model mediated
      by the confinement is found to best describe the phenomenon.

PMID- 24289682
TI  - Ultracold hydrogen atoms: a versatile coolant to produce ultracold molecules.
AB  - We show theoretically that ultracold hydrogen atoms have very favorable
      properties for sympathetic cooling of molecules to microkelvin temperatures. We
      calculate the potential energy surfaces for spin-polarized interactions of H
      atoms with the prototype molecules NH(3Sigma-) and OH(2Pi) and show that they are
      shallow (50 to 80  cm(-1)) and only weakly anisotropic. We carry out quantum
      collision calculations on H+NH and H+OH and show that the ratio of elastic to
      inelastic cross sections is high enough to allow sympathetic cooling from
      temperatures well over 1 K for NH and around 250 mK for OH.

PMID- 24289683
TI  - Excitation with effective subcycle laser pulses.
AB  - We have used laser pulses with a temporally shaped polarization to demonstrate
      the multiphoton excitation of the xenon 5g state within a subcycle of a laser
      pulse. Our polarization gated laser pulses are composed of circularly polarized
      sections at the leading and trailing edges of the pulse and of an experimentally
      defined linearly polarized central part. Only the linear part (the gate) of the
      pulse can excite neutral xenon in the 5g state. The transition cannot be driven
      with circularly polarized light because the number of photons needed would cause
      a violation of selection rules for the change of the magnetic quantum number. We
      show that the linearly polarized central part can be reduced to a subcycle pulse.
      This allows us to study excitation with an effective pulse as short as 2.3 fs at
      800 nm. Electron imaging spectroscopy has been used to visualize the presence of
      excited states as a function of the pulse duration of the gate. 

PMID- 24289684
TI  - New light shed on charge transfer in fundamental H+ + H2 collisions.
AB  - There is no consensus on the magnitude and shape of the charge transfer cross
      section in low-energy H+ + H2 collisions, in spite of the fundamental importance
      of these collisions. Experiments have thus been carried out in the energy range
      15<=E<=5000  eV. The measurements invalidate previous recommended data for E<=200
      eV and confirm the existence of a local maximum around 45 eV, which was
      predicted theoretically. Additionally, vibrationally resolved cross sections
      allow us to investigate the evolution of the underlying charge transfer mechanism
      as a function of E.

PMID- 24289685
TI  - Narrow optical homogeneous linewidths in rare earth doped nanocrystals.
AB  - A homogeneous linewidth of 85.6+/-4.4  kHz is reported in 60 nm Eu3+ doped Y2O3
      nanocrystals at 1.3 K. This linewidth was measured by two-pulse photon echoes on
      highly scattering powders using heterodyne detection. Spectral diffusion was also
      investigated by three-pulse photon echoes and resulted in a limited broadening of
      the homogenous linewidth of about 250 kHz over 120  MUs. Compared to achievable
      Rabi frequencies, in the range of several MHz, these values show that rare earth
      doped nanocrystals can be useful for applications in optical quantum information
      processing.

PMID- 24289686
TI  - Controlling the flow of light using the inhomogeneous effective gauge field that
      emerges from dynamic modulation.
AB  - We show that the effective gauge field for photons provides a versatile platform
      for controlling the flow of light. As an example we consider a photonic resonator
      lattice where the coupling strength between nearest neighbor resonators are
      harmonically modulated. By choosing different spatial distributions of the
      modulation phases, and hence imposing different inhomogeneous effective magnetic
      field configurations, we numerically demonstrate a wide variety of propagation
      effects including negative refraction, one-way mirror, and on- and off-axis
      focusing. Since the effective gauge field is imposed dynamically after a
      structure is constructed, our work points to the importance of the temporal
      degree of freedom for controlling the spatial flow of light. 

PMID- 24289687
TI  - Nonlinear surface-plasmon whispering-gallery modes in metallic nanowire cavities.
AB  - We demonstrate that the surface second-harmonic generation can lead to the
      formation of nonlinear plasmonic whispering-gallery modes (WGMs) in microcavities
      made of metallic nanowires. Since these WGMs are excited by induced surface
      nonlinear dipoles, they can be generated even when they are not coupled to the
      radiation continuum. Consequently, the quality factor of these nonlinear modes
      can be as large as the theoretical limit imposed by the optical losses in the
      metal. Remarkably, our theoretical analysis shows that nonlinear plasmonic WGMs
      are characterized by fractional azimuthal modal numbers. This suggests that the
      plasmonic cavities investigated here can be used to generate multicolor optical
      fields with fractional angular momentum. Applications to plasmonic sensors are
      also discussed. 

PMID- 24289676
TI  - Direct measurement of the total decay width of the top quark.
AB  - We present a measurement of the total decay width of the top quark using events
      with top-antitop quark pair candidates reconstructed in the final state with one
      charged lepton and four or more hadronic jets. We use the full Tevatron run II
      data set of sqrt[s]=1.96  TeV proton-antiproton collisions recorded by the CDF II
      detector. The top quark mass and the mass of the hadronically decaying W boson
      are reconstructed for each event and compared with distributions derived from
      simulated signal and background samples to extract the top quark width (Gammatop)
      and the energy scale of the calorimeter jets with in situ calibration. For a top
      quark mass Mtop=172.5  GeV/c2, we find 1.10<Gammatop<4.05  GeV at 68% confidence
      level, which is in agreement with the standard model expectation of 1.3 GeV and
      is the most precise direct measurement of the top quark width to date.

PMID- 24289688
TI  - Multiplicity of singular synchronous states in the Kuramoto model of coupled
      oscillators.
AB  - We study the Kuramoto model of globally coupled oscillators with a biharmonic
      coupling function. We develop an analytic self-consistency approach to find
      stationary synchronous states in the thermodynamic limit and demonstrate that
      there is a huge multiplicity of such states, which differ microscopically in the
      distributions of locked phases. These synchronous regimes already exist prior to
      the linear instability transition of the fully asynchronous state. In the
      presence of white Gaussian noise, the multiplicity is lifted, but the dependence
      of the order parameters on coupling constants remains nontrivial. 

PMID- 24289689
TI  - Ultrasonically encoded photoacoustic flowgraphy in biological tissue.
AB  - Blood flow speed is an important functional parameter. Doppler ultrasound
      flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of
      millimeters per second) in deep tissue. To address this challenge, we developed
      ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal
      tagging with photoacoustic imaging. Focused ultrasound generates a confined heat
      source in acoustically absorptive fluid. Thermal waves propagate with the flow
      and are directly visualized in pseudo color using photoacoustic computed
      tomography. The Doppler shift is employed to calculate the flow speed. This
      method requires only acoustic and optical absorption, and thus is applicable to
      continuous fluid. A blood flow speed as low as 0.24  mm.s(-1)} was successfully
      measured. Deep blood flow imaging was experimentally demonstrated under 5-mm
      thick chicken breast tissue.

PMID- 24289690
TI  - Critical magnetic field strength for suppression of the Richtmyer-Meshkov
      instability in plasmas.
AB  - The critical strength of a magnetic field required for the suppression of the
      Richtmyer-Meshkov instability (RMI) is investigated numerically by using a two
      dimensional single-mode analysis. For the cases of magnetohydrodynamic parallel
      shocks, the RMI can be stabilized as a result of the extraction of vorticity from
      the interface. A useful formula describing a critical condition for
      magnetohydrodynamic RMI is introduced and is successfully confirmed by direct
      numerical simulations. The critical field strength is found to be largely
      dependent on the Mach number of the incident shock. If the shock is strong
      enough, even low-beta plasmas can be subject to the growth of the RMI. 

PMID- 24289691
TI  - Turbulence-driven bootstrap current in low-collisionality tokamaks.
AB  - Neoclassical bootstrap current is expected to provide a significant fraction of
      the equilibrium plasma current in tokamak reactors. Here we report a novel
      mechanism through which a bootstrap current may be driven even in a collisionless
      plasma. In analogy with the neoclassical mechanism, in which the collisional
      equilibrium established between trapped and passing electrons produces a steady
      state current, we show that resonant scattering of electrons by drift wave
      microturbulence provides an additional means of determining the equilibrium
      between trapped and passing electrons and thus driving a bootstrap current.
      Employing a linearized Fokker-Planck collision operator, the plasma current in
      the presence of both collisions and resonant electron scattering is computed,
      allowing for the relative strength of these two mechanisms to be quantified as a
      function of collisionality and fluctuation amplitude. 

PMID- 24289692
TI  - Nanosecond pulses in a THz gyrotron oscillator operating in a mode-locked self
      consistent Q-switch regime.
AB  - An experimental study of a nanosecond pulsed regime in a THz gyrotron oscillator
      operating in a self-consistent Q-switch regime has been carried out. The gyrotron
      is operated in the TE(7,2) transverse mode radiating at a frequency of 260.5 GHz.
      The 5 W nanosecond pulses are obtained in a self-consistent Q-switch regime in
      which the cavity diffraction quality factor dynamically varies by nearly 2 orders
      of magnitude on a subnanosecond time scale via the nonlinear interaction of
      different mode-locked frequency-equidistant sidebands. The experimental results
      are in good agreement with numerical simulations performed with the TWANG code
      based on a slow time scale formulation of the self-consistent time-dependent
      nonlinear wave particle interaction equations.

PMID- 24289693
TI  - Experimental realization of Josephson junctions for an atom SQUID.
AB  - We report the creation of a pair of Josephson junctions on a toroidal dilute gas
      Bose-Einstein condensate (BEC), a configuration that is the cold atom analog of
      the well-known dc superconducting quantum interference device (SQUID). We observe
      Josephson effects, measure the critical current of the junctions, and find
      dynamic behavior that is in good agreement with the simple Josephson equations
      for a tunnel junction with the ideal sinusoidal current-phase relation expected
      for the parameters of the experiment. The junctions and toroidal trap are created
      with the painted potential, a time-averaged optical dipole potential technique
      which will allow scaling to more complex BEC circuit geometries than the single
      atom-SQUID case reported here. Since rotation plays the same role in the atom
      SQUID as magnetic field does in the dc SQUID magnetometer, the device has
      potential as a compact rotation sensor. 

PMID- 24289677
TI  - Nuclear modification of psi', chic, and J/psi production in d+Au collisions at
      sqrt[s(NN)]=200  GeV.
AB  - We present results for three charmonia states (psi', chic, and J/psi) in d+Au
      collisions at |y|<0.35 and sqrt[s(NN)]=200  GeV. We find that the modification of
      the psi' yield relative to that of the J/psi scales approximately with charged
      particle multiplicity at midrapidity across p+A, d+Au, and A+A results from the
      Super Proton Synchrotron and the Relativistic Heavy Ion Collider. In large-impact
      parameter collisions we observe a similar suppression for the psi' and J/psi,
      while in small-impact-parameter collisions the more weakly bound psi' is more
      strongly suppressed. Owing to the short time spent traversing the Au nucleus, the
      larger psi' suppression in central events is not explained by an increase of the
      nuclear absorption owing to meson formation time effects.

PMID- 24289694
TI  - XYZ quantum Heisenberg models with p-orbital bosons.
AB  - We demonstrate how the spin-1/2 XYZ quantum Heisenberg model can be realized with
      bosonic atoms loaded in the p band of an optical lattice in the Mott regime. The
      combination of Bose statistics and the symmetry of the p-orbital wave functions
      leads to a nonintegrable Heisenberg model with antiferromagnetic couplings.
      Moreover, the sign and relative strength of the couplings characterizing the
      model are shown to be experimentally tunable. We display the rich phase diagram
      in the one-dimensional case and discuss finite size effects relevant for trapped
      systems. Finally, experimental issues related to preparation, manipulation,
      detection, and imperfections are considered. 

PMID- 24289695
TI  - Phase space crystals: a new way to create a quasienergy band structure.
AB  - A novel way to create a band structure of the quasienergy spectrum for driven
      systems is proposed based on the discrete symmetry in phase space. The system,
      e.g., an ion or ultracold atom trapped in a potential, shows no spatial
      periodicity, but it is driven by a time-dependent field coupling highly
      nonlinearly to one of its degrees of freedom (e.g., ~q(n)). The band structure in
      quasienergy arises as a consequence of the n-fold discrete periodicity in phase
      space induced by this driving field. We propose an explicit model to realize such
      a phase space crystal and analyze its band structure in the frame of a tight
      binding approximation. The phase space crystal opens new ways to engineer energy
      band structures, with the added advantage that its properties can be changed in
      situ by tuning the driving field's parameters.

PMID- 24289696
TI  - Thermal transport into graphene through nanoscopic contacts.
AB  - Superior thermal conductivity of graphene is frequently reported and used to
      justify its technical relevance for ultimately scaled devices. However, this
      extraordinary property is size dependent, and understanding of graphene's thermal
      properties in the quasiballistic thermal transport regime is lacking. To overcome
      this limitation, we directly probe local heat transfer into graphene by high
      resolution scanning thermal microscopy on amorphous silicon oxide (SiO2) and
      crystalline silicon carbide (SiC). We quantify thickness-dependent thermal
      resistance modulations at sub-10-nm lateral resolution and thermal sensitivity
      for the individual atomic layers. On SiO2, we observe a decrease of thermal
      resistance with increasing number of graphene layers. We attribute this trend to
      the spreading of heat using the thickness dependence of graphene's thermal
      conductivity. On SiC, the heated tip-sample contact is scaled below the phonon
      mean free path of both the graphene and its supporting substrate. Consistently,
      we find the thermal interface resistances of the graphene top and bottom contacts
      dominating thermal transport.

PMID- 24289697
TI  - Titration of Ce3+ ions in the CeO2(111) surface by Au adatoms.
AB  - The role of surface and subsurface O vacancies for gold adsorption on crystalline
      CeO2(111) films has been investigated by scanning tunneling microscopy and
      density functional theory. Whereas surface vacancies serve as deep traps for the
      Au atoms, subsurface defects promote the formation of characteristic Au pairs
      with a mean atom distance of two ceria lattice constants (7.6 A). Hybrid density
      functional theory calculations reveal that the pair formation arises from a
      titration of the two Ce3+ ions generated by a single O vacancy. The Au-Ce3+ bond
      forms due to a strain effect, as the associated charge transfer from the spacious
      Ce3+ into the adgold enables a substantial relaxation of the ceria lattice. Also
      the experimentally determined Au-pair length is reproduced in the calculations,
      as we find a Ce3+-Ce3+ spacing of two ceria lattice parameters to be
      energetically preferred. Single Au atoms can thus be taken as position markers
      for Ce3+ ion pairs in the surface, providing unique information on electron
      localization phenomena in reduced ceria.

PMID- 24289698
TI  - Non-Fermi-liquid and topological states with strong spin-orbit coupling.
AB  - We argue that a class of strongly spin-orbit-coupled materials, including some
      pyrochlore iridates and the inverted band gap semiconductor HgTe, may be
      described by a minimal model consisting of the Luttinger Hamiltonian supplemented
      by Coulomb interactions, a problem studied by Abrikosov and collaborators. It
      contains twofold degenerate conduction and valence bands touching quadratically
      at the zone center. Using modern renormalization group methods, we update and
      extend Abrikosov's classic work and show that interactions induce a quantum
      critical non-Fermi-liquid phase, stable provided time-reversal and cubic
      symmetries are maintained. We determine the universal power-law exponents
      describing various observables in this Luttinger-Abrikosov-Beneslavskii state,
      which include conductivity, specific heat, nonlinear susceptibility, and the
      magnetic Gruneisen number. Furthermore, we determine the phase diagram in the
      presence of cubic and/or time-reversal symmetry breaking perturbations, which
      includes a topological insulator and Weyl semimetal phases. Many of these phases
      possess an extraordinarily large anomalous Hall effect, with the Hall
      conductivity scaling sublinearly with magnetization sigma(xy)~M0.51.

PMID- 24289699
TI  - Emergence of domains and nonlinear transport in the zero-resistance state.
AB  - We study transport in the domain state, the so-called zero-resistance state, that
      emerges in a two-dimensional electron system in which the combined action of
      microwave radiation and magnetic field produces a negative absolute conductivity.
      We show that the voltage-biased system has a rich phase diagram in the system
      size and voltage plane, with second- and first-order transitions between the
      domain and homogeneous states for small and large voltages, respectively. We find
      the residual negative dissipative resistance in the stable domain state. 

PMID- 24289700
TI  - Self-organized topological state with Majorana fermions.
AB  - Most physical systems known to date tend to resist entering the topological phase
      and must be fine-tuned to reach that phase. Here, we introduce a system in which
      a key dynamical parameter adjusts itself in response to the changing external
      conditions so that the ground state naturally favors the topological phase. The
      system consists of a quantum wire formed of individual magnetic atoms placed on
      the surface of an ordinary s-wave superconductor. It realizes the Kitaev paradigm
      of topological superconductivity when the wave vector characterizing the emergent
      spin helix dynamically self-tunes to support the topological phase. We call this
      phenomenon a self-organized topological state. 

PMID- 24289701
TI  - Experimental evidence of hidden topological surface states in PbBi4Te7.
AB  - A topological surface state that is protected physically under the Bi2Te3-like
      five-layer block has been revealed on the Pb-based topological insulator (TI)
      PbBi4Te7 by bulk sensitive angle-resolved photoelectron spectroscopy (ARPES).
      Furthermore, conservation of the spin polarization of the hidden topological
      surface states is directly confirmed by bulk-sensitive spin ARPES observation.
      This finding paves the way to realize the real spintronics devices by TIs that
      are operable in the real environment.

PMID- 24289702
TI  - Multiband superconductivity of heavy electrons in a TlNi2Se2 single crystal.
AB  - We have made the first observation of superconductivity in TlNi2Se2 at T(C)=3.7 
      K, and it appears to involve heavy electrons with an effective mass m*=(14
      20)m(b), as inferred from the normal-state electronic specific heat and the upper
      critical field, H(C2)(T). We found that the zero-field electronic specific-heat
      data, C(es)(T) (0.5  K<=T<3.7  K) in the superconducting state can be fitted with
      a two-gap BCS model, indicating that TlNi2Se2 seems to be a multiband
      superconductor, which is consistent with the band calculation for the
      isostructural KNi2S2. It is also found that the electronic specific-heat
      coefficient in the mixed state gammaN(H) exhibits a H(1/2) behavior, which is
      considered as a common feature of the d-wave superconductors. TlNi2Se2, as a d
      electron system with heavy electron superconductivity, may be a bridge between
      cuprate- or iron-based and conventional heavy-fermion superconductors.

PMID- 24289703
TI  - Measurement of a double neutron-spin resonance and an anisotropic energy gap for
      underdoped superconducting NaFe0.985Co0.015As using inelastic neutron scattering.
AB  - We use inelastic neutron scattering to show that superconductivity in electron
      underdoped NaFe0.985Co0.015As induces a dispersive sharp resonance near
      E(r1)=3.25  meV and a broad dispersionless mode at E(r2)=6  meV. However, similar
      measurements on overdoped superconducting NaFe0.935Co0.045As find only a single
      sharp resonance at E(r)=7  meV. We connect these results with the observations of
      angle-resolved photoemission spectroscopy that the superconducting gaps in the
      electron Fermi pockets are anisotropic in the underdoped material but become
      isotropic in the overdoped case. Our analysis indicates that both the double
      neutron spin resonances and gap anisotropy originate from the orbital dependence
      of the superconducting pairing in the iron pnictides. Our discovery also shows
      the importance of the inelastic neutron scattering in detecting the multiorbital
      superconducting gap structures of iron pnictides.

PMID- 24289704
TI  - Proposed method for tunneling spectroscopy with ohmic dissipation using resistive
      electrodes: a possible Majorana filter.
AB  - We propose a scheme to distinguish zero-energy peaks due to Majorana from those
      due to other effects at finite temperature by simply replacing the normal
      metallic lead with a resistive lead (large R~kOmega) in the tunneling
      spectroscopy. The dissipation effects due to the large resistance change the
      tunneling conductance significantly in different ways. The Majorana peak remains
      increase as temperature decreases G~T(2r-1) for r=e2R/h<1/2. The zero-energy peak
      due to other effects splits into two peaks at finite temperature and the
      conductance at zero voltage bias varies with temperature by a power law. The
      dissipative tunneling with a Majorana mode belongs to the same universal class as
      the unstable critical point of the case with a non-Majorana mode.

PMID- 24289705
TI  - Amplitude fluctuations driven by the density of electron pairs within nanosize
      granular structures inside strongly disordered superconductors: evidence for a
      shell-like effect.
AB  - Motivated by the recent observation of the shell effect in a nanoscale pure
      superconductor by Bose et al. [Nat. Mater. 9, 550 (2010)], we explore the
      possible shell-like effect in a strongly disordered superconductor as it is known
      to produce nanosize superconducting puddles (SPs). We find a remarkable change in
      the texture of the pairing amplitudes that is responsible for forming the SP,
      upon monotonic tuning of the average electron density, <n>, and keeping the
      disorder landscape unaltered. Both the spatially averaged pairing amplitude and
      the quasiparticle excitation gap oscillate with <n>. This oscillation is due to a
      rapid change in the low-lying quasiparticle energy spectra and thereby a change
      in the shapes and positions of the SPs. We establish a correlation between the
      formation of SPs and the shell-like effect. The experimental consequences of our
      theory are also discussed.

PMID- 24289706
TI  - Coexistence of cluster spin glass and superconductivity in Ba(Fe(1-x)Co(x))2As2
      for 0.060<=x<=0.071.
AB  - We present 75As nuclear magnetic resonance data from measurements of a series of
      Ba(Fe(1-x)Co(x))2As2 crystals with 0.00<=x<=0.075 that reveals the coexistence of
      frozen antiferromagnetic domains and superconductivity for 0.060<=x<=0.071.
      Although bulk probes reveal no long range antiferromagnetic order beyond x=0.06,
      we find that the local spin dynamics reveal no qualitative change across this
      transition. The characteristic domain sizes vary by more than an order of
      magnitude, reaching a maximum variation at x=0.06. This inhomogeneous glassy
      dynamics may be an intrinsic response to the competition between
      superconductivity and antiferromagnetism in this system.

PMID- 24289707
TI  - Spread of correlations in long-range interacting quantum systems.
AB  - The nonequilibrium response of a quantum many-body system defines its fundamental
      transport properties and how initially localized quantum information spreads.
      However, for long-range-interacting quantum systems little is known. We address
      this issue by analyzing a local quantum quench in the long-range Ising model in a
      transverse field, where interactions decay as a variable power law with distance
      ?r(-alpha), alpha>0. Using complementary numerical and analytical techniques, we
      identify three dynamical regimes: short-range-like with an emerging light cone
      for alpha>2, weakly long range for 1<alpha<2 without a clear light cone but with
      a finite propagation speed of almost all excitations, and fully nonlocal for
      alpha<1 with instantaneous transmission of correlations. This last regime breaks
      generalized Lieb-Robinson bounds and thus locality. Numerical calculation of the
      entanglement spectrum demonstrates that the usual picture of propagating
      quasiparticles remains valid, allowing an intuitive interpretation of our
      findings via divergences of quasiparticle velocities. Our results may be tested
      in state-of-the-art trapped-ion experiments.

PMID- 24289708
TI  - Feedback-enhanced parametric squeezing of mechanical motion.
AB  - We present a single-quadrature feedback scheme able to overcome the conventional
      3 dB limit on parametric squeezing. The method is experimentally demonstrated in
      a micromechanical system based on a cantilever with a magnetic tip. The
      cantilever is detected at low temperature by a SQUID susceptometer, while
      parametric pumping is obtained by modulating the magnetic field gradient at twice
      the cantilever frequency. A maximum squeezing of 11.5 dB and 11.3 dB is observed,
      respectively, in the response to a sinusoidal test signal and in the
      thermomechanical noise. So far, the maximum squeezing factor is limited only by
      the maximum achievable parametric modulation. The proposed technique might be
      used to squeeze one quadrature of a mechanical resonator below the quantum noise
      level, even without the need for a quantum limited detector. 

PMID- 24289709
TI  - Loss of collective motion in swarming bacteria undergoing stress.
AB  - The collective motion of Bacillus subtilis in the presence of a photosensitizer
      is disrupted by reactive oxygen species when exposed to light of sufficient
      dosages and is partially recovered when light irradiation is suspended. The
      transition from a highly collective to a more random motion is modeled using an
      improved self-propelled model with alignment rule. The increment in noise level
      describes the enhanced uncertainty in the motion of swarming bacteria under
      stress as observed experimentally. 

PMID- 24289711
TI  - Glassy states in asymmetric mixtures of soft and hard colloids.
AB  - By employing rheological experiments, mode coupling theory, and computer
      simulations based on realistic coarse-grained models, we investigate the effects
      of small, hard colloids on the glassy states formed by large, soft colloids.
      Multiarm star polymers mimic hard and soft colloids by appropriately varying the
      number and size of their arms. The addition of hard colloids leads, depending on
      their concentration, to either melting of the soft glass or the emergence of two
      distinct glassy states. We explain our findings by depletion of the colloids
      adjacent to the stars, which leads to an arrested phase separation when the
      repulsive glass line meets the demixing binodal. The parameter-free agreement
      between experiment, theory, and simulations suggests the generic nature of our
      results and opens the route for designing soft-hard colloidal composites with
      tunable rheology. 

PMID- 24289710
TI  - Bursts of active transport in living cells.
AB  - We show, using a large new data set, that the temporally resolved speed of active
      cargo transport in living cells follows a scaling law over several decades of
      time and length. The statistical regularities display a time-averaged shape that
      we interpret to reflect stress buildup, followed by rapid release. The scaling
      power law agrees quantitatively with those reported in inanimate systems (jammed
      colloids and granular media, and magnetic Barkhausen noise), suggesting a common
      origin in pushing through a crowded environment in a weak force regime. The
      implied regulation of the speed of active cellular transport due to environmental
      obstruction results in bursts of speed and acceleration. These findings extend
      the classical notion of molecular crowding. 

PMID- 24289712
TI  - Casting light on the darkening of colors in historical paintings.
AB  - The degradation of colors in historical paintings affects our cultural heritage
      in both museums and archeological sites. Despite intensive experimental studies,
      the origin of darkening of one of the most ancient pigments known to humankind,
      vermilion (alpha-HgS), remains unexplained. Here, by combining many-body
      theoretical spectroscopy and high-resolution microscopic x-ray diffraction, we
      clarify the composition of the damaged paint work and demonstrate possible
      physicochemical processes, induced by illumination and exposure to humidity and
      air, that cause photoactivation of the original pigment and the degradation of
      the secondary minerals. The results suggest a new path for the darkening process
      which was never considered by previous studies and prompt a critical examination
      of their findings. 

PMID- 24289713
TI  - Comment on "Effects of particle shape on growth dynamics at edges of evaporating
      drops of colloidal suspensions".

PMID- 24289714
TI  - Yunker et al. reply.

PMID- 24289716
TI  - Retraction notice: Odanacatib for the treatment of postmenopausal osteoporosis.

PMID- 24289715
TI  - A pilot randomized controlled trial to increase smoking cessation by maintaining
      National Health Service Stop Smoking Service attendance.
AB  - OBJECTIVES: The National Health Service (NHS) Stop Smoking Service (SSS) is an
      extremely cost-effective method of enabling smoking cessation. However, the SSS
      is only used by a minority of smokers. Developing interventions to maintain
      service attendance may help to increase the number of quitters. This study pilots
      an intervention aimed at maintaining attendance by (1) increasing motivation to
      attend through a booklet providing evidence of service effectiveness and (2)
      strengthening the link between motivation to attend and attendance through
      forming an implementation intention. DESIGN: A factorial randomized controlled
      trial. METHODS: A total of 160 newly enrolled smokers at the Surrey NHS SSS were
      recruited and randomly assigned to one of four conditions: (1) standard care
      (SC), (2) SC + effectiveness booklet, (3) SC + implementation intention, and (4)
      SC + effectiveness booklet + implementation intention. The outcome measures
      included attendance at the SSS and the 4-week quit rate. RESULTS: The booklet
      increased service attendance (OR = 2.93, p < .01, 95% CI = 1.45-5.93; Number
      Needed to Treat = 3.3) but had no impact on the 4-week quit rate (OR = 1.55, 95%
      CI = 0.75-3.21). Forming an implementation intention had no impact on service
      attendance or the 4-week quit rate. Attending the service was associated with a
      higher 4-week quit rate (rho = 87.52, p < .001). CONCLUSIONS: Presenting
      information about the effectiveness of the service improved service attendance. A
      larger trial now needs to evaluate whether this intervention can also increase
      the quit rate. STATEMENT OF CONTRIBUTION: What is already known on this subject?
      The NHS Stop Smoking Service is an effective yet underused method of enabling
      smoking cessation. Low uptake levels may be due to smokers' misconception that
      the service will not improve their chances of quitting successfully. Improving
      smokers' perceptions of service efficacy may be valuable for maintaining service
      attendance, and subsequently improving smoking cessation levels in the United
      Kingdom. What does this study add? This pilot randomized controlled trial is the
      first to target service attendance rather than cessation levels. The results
      demonstrate that providing evidence of service efficacy in a simple icon array
      format can significantly improve service attendance.

PMID- 24289717
TI  - Novel rescue procedure for inferior vena cava reconstruction in living-donor
      liver transplantation using a vascular graft recovered 25 h after donors'
      circulatory death and systematic review.
AB  - Liver transplantation is a lifesaving treatment for patients suffering from end
      stage liver disease. Rarely, acute congestion of the inferior vena cava (IVC) is
      being encountered because of tumor compression. MELD allocation does not reflect
      severity of this condition because of lack of organ failure. Herein, a patient is
      being presented undergoing urgent living-donor liver transplantation (LDLT) with
      IVC reconstruction for a fast-growing hepatic epithelioid hemangioendothelioma
      (HEH). IVC reconstruction using a venous graft recovered from a 25-h after
      circulatory-death prior transplantation became necessary to compensate severe
      venous congestion. Additionally, a systematic review of the literature searching
      MEDLINE/PubMed was performed. Protocol and eligibility criteria were specified in
      advance and registered at the PROSPERO registry (CRD42013004827). Published
      literature of IVC reconstruction in LDLT was selected. Two reports describing IVC
      reconstruction with cryopreserved IVC grafts and one IVC reconstruction using a
      deceased after-circulatory-death-donor IVC graft were included. Follow-up was at
      12 and 13 months, respectively. Regarding the graft recovery in the setting of
      living-related donation, this graft remained patent during the nine-month follow
      up period. This is the first report on the use of a venous graft from a
      circulatory-death-donor, not eligible for whole organ recovery. We demonstrate in
      this study the feasibility of using a size and blood-group-compatible IVC graft
      from a cold-stored donor, which can solve the problem of urgent IVC
      reconstruction in patients undergoing LDLT.

PMID- 24289718
TI  - Urban lymphatic filariasis in the metropolis of Dar es Salaam, Tanzania.
AB  - BACKGROUND: The last decades have seen a considerable increase in urbanization in
      Sub-Saharan Africa, and it is estimated that over 50% of the population will live
      in urban areas by 2040. Rapid growth of cities combined with limited economic
      resources often result in informal settlements and slums with favorable
      conditions for proliferation of vectors of lymphatic filariasis (LF). In Dar es
      Salaam, which has grown more than 30 times in population during the past 55 years
      (4.4 million inhabitants in 2012), previous surveys have indicated high
      prevalences of LF. This study investigated epidemiological aspects of LF in Dar
      es Salaam, as a background for planning and implementation of control. METHODS:
      Six sites with varying distance from the city center (3-30 km) and covering
      different population densities, socioeconomic characteristics, and water,
      sewerage and sanitary facilities were selected for the study. Pupils from one
      public primary school at each site were screened for circulating filarial antigen
      (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure
      to transmission). Community members were examined for CFA, microfilariae and
      chronic manifestations. Structured questionnaires were administered to pupils and
      heads of community households, and vector surveys were carried out in selected
      households. RESULTS: The study indicated that a tremendous decrease in the burden
      of LF infection had occurred, despite haphazard urbanisation. Contributing
      factors may be urban malaria control targeting Anopheles vectors, short survival
      time of the numerous Culex quinquefasciatus vectors in the urban environment,
      widespread use of bed nets and other mosquito proofing measures, and mass drug
      administration (MDA) in 2006 and 2007. Although the level of ongoing transmission
      was low, the burden of chronic LF disease was still high. CONCLUSIONS: The
      development has so far been promising, but continued efforts are necessary to
      ensure elimination of LF as a public health problem. These will include improving
      the awareness of people about the role of mosquitoes in transmission of LF, more
      thorough implementation of environmental sanitation to reduce Cx.
      quinquefasciatus breeding, continued MDA to high-risk areas, and set-up of
      programmes for management of chronic LF disease.

PMID- 24289719
TI  - Surgical trials and trial registers: a cross-sectional study of randomized
      controlled trials published in journals requiring trial registration in the
      author instructions.
AB  - BACKGROUND: Trial registration and the reporting of trial results are essential
      to increase transparency in clinical research. Although both have been strongly
      promoted in recent years, it remains unclear whether they have been successfully
      implemented in surgery and surgery-related disciplines. In this cross-sectional
      study, we assessed whether randomized controlled trials (RCTs) published in
      surgery journals requiring trial registration in their author instructions were
      indeed registered, and whether the study results of registered RCTs had been
      submitted to the trial register and were thus publicly available. METHODS: The
      ten highest ranked surgery journals requiring trial registration by impact factor
      (Journal Citation Reports, JCR, 2011) were chosen. We then searched MEDLINE (in
      PubMed) for RCTs published in the selected journals between 1 June 2012 and 31
      December 2012. Any trials recruiting participants before 2004 were excluded
      because the International Committee of Medical Journal Editors (ICMJE) first
      proposed trial registration in 2004. We then searched the World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to
      assess whether the identified RCTs were indeed registered and whether the results
      of the registered RCTs were available in the register. RESULTS: The search
      retrieved 588 citations. Four hundred and sixty references were excluded in the
      first screening. A further 25 were excluded after full-text screening. A total of
      103 RCTs were finally included. Eighty-five of these RCTs (83%) could be found
      via the ICTRP. For 7 of 59 (12%) RCTs, which were registered on
      ClinicalTrials.gov, summary study data had been posted in the results database.
      CONCLUSIONS: Although still not fully implemented, trial registration in surgery
      has gained momentum. In general, however, the submission of summary study data to
      ClinicalTrials.gov remains poor.

PMID- 24289720
TI  - Surgical techniques and results of the pulmonary artery reconstruction for
      patients with central non-small cell lung cancer.
AB  - BACKGROUND: It is difficult to achieve a margin-negative resection (R0) for non
      small cell lung cancer (NSCLC) patients with infiltration of the pulmonary
      artery. We report our experience of the pulmonary artery reconstruction with
      regard to long-term survival. METHODS: Clinical records of 118 patients with
      NSCLC who underwent partial or circumferential pulmonary artery resection during
      a 21-year period were reviewed retrospectively. Techniques and survival outcomes
      were analyzed. RESULTS: We performed 22 pulmonary artery sleeve resections, 51
      reconstructions by autologous pericardial patch, 36 tangential resections, 3 left
      main pulmonary artery (PA) angioplasties during pneumonectomy without
      cardiopulmonary bypass, and 6 by only preserving the apical and anterior (1(st))
      branch of pulmonary arterial trunk. In 41 patients, bronchial sleeve resection
      was associated; in 7 cases, superior vena cava reconstruction was also required.
      Thirty-one patients received induction therapy. Thirteen patients had stage IB
      disease, 41 stage II, 53 IIIA, and 11 IIIB. Ninety-three patients had squamous
      cell carcinoma, 22 adenocarcinoma, 2 mixed and 1 large cell carcinoma. Negative
      vascular margins were achieved in all. 5 positive bronchial margins were due to
      limited lung function. The analysis of 118 cases yielded follow-up data in 94
      cases. The mean follow-up was 70 months (range 1-156 months). There was no in
      hospital death, and the overall 5-year survival was 50.2%. Five-year survivals
      for stages I and II versus III were 63.9% versus 37.0% (p = 0.0059). Multivariate
      analysis yielded non-squamous cell carcinoma, stage III and patch pulmonary
      arterioplasty as negative prognosis factors. PA reconstruction associated with
      bronchial sleeve resection was the positive prognostic factor. CONCLUSIONS:
      Pulmonary artery resection and reconstruction is feasible and safe, with
      favorable long-term survival. Our results support this technique as an effective
      alternative to selected patients with infiltration of the pulmonary artery, such
      as stage I and II and those who proved down-staged from stage III. Accurate
      preoperative evaluation, precise and suitable surgical techniques are crucial to
      achieve good results. Only preserving the anterior and apical pulmonary arteries
      and reconstruction of the main pulmonary artery by using the artery conduit
      technique without cardiopulmonary bypass in association with left pneumonectomy
      can be performed successfully. Postoperative anticoagulation is unnecessary.

PMID- 24289721
TI  - Functional social support, psychological capital, and depressive and anxiety
      symptoms among people living with HIV/AIDS employed full-time.
AB  - BACKGROUND: Psychological distress (e.g., depression and anxiety) has been
      regarded as the main cause of leaving work for people living with HIV/AIDS
      (PLWHA) in workplaces. This study aims to explore the associations of functional
      social support (FSS) and psychological capital (PC) with depressive and anxiety
      symptoms among PLWHA employed full-time. METHODS: This cross-sectional study was
      performed in Liaoning, China, during the period of December 2010-April 2011. The
      Center for Epidemiologic Studies Depression Scale, the Zung Self-Rating Anxiety
      Scale, the Duke-UNC Functional Social Support Questionnaire, and the
      Psychological Capital Questionnaire were completed by PLWHA employed full-time.
      Structural equation modeling was used to test the proposed relationships between
      variables. Asymptotic and resampling strategies were performed to explore the
      mediating roles of PC and its components (self-efficacy, hope, optimism,
      resilience). RESULTS: Of 320 participants surveyed, 66.3% had depressive
      symptoms, and 45.6% had anxiety symptoms. Significant negative associations of
      FSS and PC with depressive and anxiety symptoms were revealed. PC (a*b = -0.209,
      BCa 95% CI: -0.293, -0.137, p < 0.05), hope (a*b = -0.103, BCa 95% CI: -0.192, 
      0.034, p < 0.05), and optimism (a*b = -0.047, BCa 95% CI: -0.106, -0.008, p <
      0.05) significantly mediated the association between FSS and depressive symptoms.
      PC (a*b = -0.151, BCa 95% CI: -0.224, -0.095, p < 0.05) and self-efficacy (a*b = 
      0.080, BCa 95% CI: -0.158, -0.012, p < 0.05) significantly mediated the FSS
      anxiety symptoms association. CONCLUSIONS: FSS and PC could help reduce
      depressive and anxiety symptoms among PLWHA employed full-time. PC fully mediates
      the associations of FSS with depressive and anxiety symptoms. In addition to
      enhancing FSS, PC development could be included in the prevention and treatment
      strategies for depressive and anxiety symptoms targeted at PLWHA employed full
      time.

PMID- 24289722
TI  - Added value of Gd-EOB-DTPA-enhanced Hepatobiliary phase MR imaging in evaluation
      of focal solid hepatic lesions.
AB  - BACKGROUND: Correct characterization of focal solid hepatic lesions has always
      been a challenge and is of great diagnostic and therapeutic relevance. The
      purpose of this study was to determine the added value of hepatobiliary phase
      images in Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for
      differentiating focal solid hepatic lesions. METHODS: In this retrospective trial
      84 consecutive patients underwent Gd-EOB-DTPA-enhanced MR examinations. MRI was
      conducted for 64 patients with malignant focal hepatic lesions (34 hepatocellular
      carcinoma (HCC), 30 metastases) and for 20 patients with benign hepatic lesions
      (14 focal nodular hyperplasia (FNH), 3 adenoma, 3 hemangioma). Five radiologists
      independently reviewed three sets of MR images by means of a 5-point confidence
      scale from score 1 (definitely benign) to score 5 (definitely malignant): set 1:
      unenhanced images; set 2: unenhanced and Gd-EOB-DTPA-enhanced dynamic images; set
      3: hepatobiliary phase images in addition to set 2. Accuracy was assessed by the
      alternative free-response receiver operating characteristic curve (Az) and the
      index of diagnostic performance was calculated. RESULTS: Diagnostic accuracy was
      significantly improved by the addition of Gd-EOB-DTPA-enhanced dynamic images: Az
      in set 1 was 0.708 and 0.833 in set 2 (P = 0.0002). The addition of hepatobiliary
      phase images increased the Az value to 0.941 in set 3 (set 3 vs set 2, P <
      0.0001; set 3 vs set 1, P < 0.0001). The index of diagnostic performance was
      lowest in set 1 (45%), improved in set 2 (71%), and highest in set 3 (94%).
      CONCLUSIONS: Hepatobiliary phase images obtained after Gd-EOB-DTPA-enhanced
      dynamic MRI improve the differentiation of focal solid hepatic lesions.

PMID- 24289723
TI  - Evaluation of health-related physical fitness parameters and association analysis
      with depression, anxiety, and quality of life in patients with fibromyalgia.
AB  - AIM: The purpose of this study was to investigate the physical fitness parameters
      (maximal aerobic capacity, muscle strength and flexibility), daily physical
      activity, resting metabolic rate (RMR), pulmonary function tests (PFTs), body
      composition, depression, anxiety and health-related quality of life (HRQoL)
      changes as well as the associations among these parameters in patients with
      fibromyalgia and to compare them with healthy controls. METHODS: Thirty-nine
      women with fibromyalgia and 40 controls were included in this study. Physical
      measurements, HRQoL questionnaire, Beck Depression Inventory (BDI) score and Beck
      Anxiety Inventory (BAI) score were applied to all participants. RESULTS: Maximal
      aerobic capacity, trunk flexibility, daily step numbers, total energy
      expenditure, RMR and PFT values were not significantly different between the
      patients and the controls. Fibromyalgia patients had higher daily moderate
      activity times, active energy expenditure values, and BDI and BAI scores, while
      their lower handgrip strength and back-leg strength values and Short-form health
      survey (SF)-36 scores were comparable to controls. Handgrip strength and back-leg
      strength values showed moderately positive correlations with SF-36 scores (total,
      physical health, mental health) and moderately negative correlations with BDI and
      BAI scores in patients with fibromyalgia. CONCLUSION: Our results suggested that
      muscle strength, HRQoL, depression and anxiety symptomatology were impaired in
      fibromyalgia patients compared to healthy controls. Low muscle strength is
      related to reduced HRQoL and increased depression and anxiety symptomatology in
      patients with fibromyalgia. Also we suggest that performing daily exercises,
      including aerobic and strength training, as part of one's lifestyle may have
      beneficial effects in fibromyalgia patients.

PMID- 24289724
TI  - Leptospiral extracellular matrix adhesins as mediators of pathogen-host
      interactions.
AB  - Leptospirosis is been considered an important infectious disease that affects
      humans and animals worldwide. This review summarizes our current knowledge of
      bacterial attachment to extracellular matrix (ECM) components and discusses the
      possible role of these interactions for leptospiral pathogenesis. Leptospiral
      proteins show different binding specificity for ECM molecules: some are exclusive
      laminin-binding proteins (Lsa24/LfhA/LenA, Lsa27), while others have broader
      spectrum binding profiles (LigB, Lsa21, LipL53). These proteins may play a
      primary role in the colonization of host tissues. Moreover, there are
      multifunctional proteins that exhibit binding activities toward a number of
      target proteins including plasminogen/plasmin and regulators of the complement
      system, and as such, might also act in bacterial dissemination and immune evasion
      processes. Many ECM-interacting proteins are recognized by human leptospirosis
      serum samples indicating their expression during infection. This compilation of
      data should enhance our understanding of the molecular mechanisms of leptospiral
      pathogenesis.

PMID- 24289727
TI  - Serelaxin: new investigational treatment in acute heart failure.
AB  - Over the last decade several pharmacological approaches for acute heart failure
      have been introduced, however, no drastic change in the medical management apart
      from device-dependent therapy was observed. Essentially vasodilators and
      diuretics as primary therapy in acute heart failure was discussed and encouraged
      in the guidelines but no breakthrough in the treatment of acute heart failure was
      achieved. More recently, clinical trials of relaxin and its recombinant form,
      i.e., serelaxin in patients with acute heart failure demonstrated a significant
      clinical improvement with favorable safety and tolerability profile in
      symptomatic heart failure patients. This report reviews the potential beneficial
      effects and role of serelaxin in the setting of acute heart failure. 

PMID- 24289725
TI  - Culture dependent and independent analysis of bacterial communities associated
      with commercial salad leaf vegetables.
AB  - BACKGROUND: Plants harbor a diverse bacterial community, both as epiphytes on the
      plant surface and as endophytes within plant tissue. While some plant-associated
      bacteria act as plant pathogens or promote plant growth, others may be human
      pathogens. The aim of the current study was to determine the bacterial community
      composition of organic and conventionally grown leafy salad vegetables at the
      point of consumption using both culture-dependent and culture-independent
      methods. RESULTS: Total culturable bacteria on salad vegetables ranged from 8.0 *
      10(3) to 5.5 * 10(8) CFU g(-1). The number of culturable endophytic bacteria from
      surface sterilized plants was significantly lower, ranging from 2.2 * 10(3) to
      5.8 * 10(5) CFU g(-1). Cultured isolates belonged to six major bacterial phyla,
      and included representatives of Pseudomonas, Pantoea, Chryseobacterium, and
      Flavobacterium. Eleven different phyla and subphyla were identified by culture
      independent pyrosequencing, with Gammaproteobacteria, Betaproteobacteria, and
      Bacteroidetes being the most dominant lineages. Other bacterial lineages
      identified (e.g. Firmicutes, Alphaproteobacteria, Acidobacteria, and
      Actinobacteria) typically represented less than 1% of sequences obtained. At the
      genus level, sequences classified as Pseudomonas were identified in all samples
      and this was often the most prevalent genus. Ralstonia sequences made up a
      greater portion of the community in surface sterilized than non-surface
      sterilized samples, indicating that it was largely endophytic, while
      Acinetobacter sequences appeared to be primarily associated with the leaf
      surface. Analysis of molecular variance indicated there were no significant
      differences in bacterial community composition between organic versus
      conventionally grown, or surface-sterilized versus non-sterilized leaf
      vegetables. While culture-independent pyrosequencing identified significantly
      more bacterial taxa, the dominant taxa from pyrosequence data were also detected
      by traditional culture-dependent methods. CONCLUSIONS: The use of pyrosequencing
      allowed for the identification of low abundance bacteria in leaf salad vegetables
      not detected by culture-dependent methods. The presence of a range of bacterial
      populations as endophytes presents an interesting phenomenon as these
      microorganisms cannot be removed by washing and are thus ingested during salad
      consumption.

PMID- 24289726
TI  - Murine analogues of etanercept and of F8-IL10 inhibit the progression of collagen
      induced arthritis in the mouse.
AB  - INTRODUCTION: Etanercept is a fusion protein consisting of the soluble portion of
      the p75-tumor necrosis factor receptor (TNFR) and the Fc fragment of human IgG1,
      which is often used for the treatment of patients with rheumatoid arthritis. F8
      IL10 is a human immunocytokine based on the F8 antibody and interleukin-10, which
      is currently being investigated in rheumatoid arthritis with promising clinical
      results. We have aimed at expressing murine versions of these two fusion
      proteins, in order to assess their pharmaceutical performance in the collagen
      induced model of rheumatoid arthritis in the mouse. METHODS: Two fusion proteins
      (termed muTNFR-Fc and F8-muIL10) were cloned, expressed in chinese hamster ovary
      (CHO) cells, purified and characterized. Biological activity of muTNFR-Fc was
      assessed by its ability to inhibit TNF-induced killing of mouse fibroblasts,
      while F8-muIL10 was characterized in terms of muIL10 activity, of binding
      affinity to the cognate antigen of F8, the alternatively-spliced EDA domain of
      fibronectin, by quantitative biodistribution analysis and in vivo imaging. The
      therapeutic activity of both fusion proteins was investigated in a collagen
      induced mouse model of arthritis. Mouse plasma was analyzed for anti-drug
      antibody formation and cytokine levels were determined by bead-based multiplex
      technology. The association of F8-IL10 proteins with blood cells was studied in a
      centrifugation assay with radiolabeled protein. RESULTS: Both fusion proteins
      exhibited excellent purity and full biological activity in vitro. In addition, F8
      muIL10 was able to localize on newly-formed blood vessels in vivo. When used in a
      murine model of arthritis, the two proteins inhibited arthritis progression. The
      activity of muTNFR-Fc was tested alone and in combination with F8-huIL10. The
      chimeric version of F8-IL10 was not better then the fully human fusion protein
      and showed similar generation of mouse anti-fusion protein antibodies. Incubation
      studies of F8-muIL10 and F8-huIL10 with blood revealed that only the fully human
      fusion protein is not associated with cellular components at concentrations as
      low as 0.2 MUg/ml, thus facilitating its extravasation from blood vessels.
      CONCLUSIONS: The described products may represent useful research tools for the
      study of the anti-arthritic properties of TNF blockade and of IL10-based
      immunocytokines in syngeneic immunocompetent models of arthritis.

PMID- 24289728
TI  - The meaning of activity and participation in everyday life when living with hand
      osteoarthritis.
AB  - OBJECTIVE: The aim of this paper is, first, to advance the understanding of
      participation and its relationship to activity; second, to add to discussions or
      understandings of the ICF by contributing an empirically derived understanding of
      participation and its relationship to activity connected to the conduct of
      everyday life in people with hand osteoarthritis (hand OA). METHODS: Semi
      structured interviews were carried out with 31 men and women living with hand OA
      because existing research on this group and the challenges they encounter in
      their everyday life is sparse. The analytical process was inspired by
      Interpretive Phenomenological Analysis and informed by critical psychology and
      social practice theory as interpretive frameworks. RESULTS: Our empirical
      findings indicate that persons with hand OA experience participation restrictions
      in their everyday lives and activity limitations as aspects of participation.
      This indicates that activity and participation are experienced as interrelated
      across social contexts. CONCLUSIONS: Participation in everyday life seems
      complex: what to participate in, how to participate and with whom seem of
      importance for subjective meaning-making. Implications are discussed in relation
      to methodology, the empirical findings, and clinical practice.

PMID- 24289729
TI  - Motivations for inadequate persistence with disease modifying anti-rheumatic
      drugs in early rheumatoid arthritis: the patient's perspective.
AB  - BACKGROUND: Knowledge of factors that contribute to non-persistence with disease
      modifying anti-rheumatic drugs (NP) is essential to improve rheumatoid arthritis
      (RA) outcomes. Aims of the study were to investigate patient's motivations and
      risk factors for NP in a cohort of early RA patients. METHODS: Up to September
      2012, data from 149 patients, who had at least 1 year of follow-up, at least one
      drug indication, and at least 2 consecutive six-months-apart rheumatic
      evaluations that included assessment of compliance were reviewed. NP and
      patient's motivations of NP were evaluated according to a questionnaire. NP was
      defined when patients referred that they had completely stop RA medication,
      "Sometimes", "Almost always" or "Always". Patients had to pay for their
      medication.Descriptive statistics and logistic regression models were used.
      Statistical significance was set at a p value of less than 0.05. The study was
      approved by the internal review board. RESULTS: Up to cut-off, 715 questionnaires
      were applied to 149 patients, who had follow-up of 58.7 +/- 27.9 months and were
      indicated 2.4 +/- 0.7 DMARDs/patient/follow-up.Patients were most frequently
      female (88.6%), middle-aged ([mean +/- SD] age of 38.5 +/- 12.8 years) with lower
      middle/lower socio-economic status (87.9%) and scholarship of 11 +/- 3.9
      years.Ninety-nine (66.4%) patients were NP and filled 330 questionnaires.
      Multivariate analysis showed that years of formal education (OR: 1.12, 95% CI:
      1.1-1.24, p = 0.03), perception of at least some difficulty to find arthritis
      medication (OR: 5.68, 95% CI: 2.48-13, p = 0.000) and perception that arthritis
      medication is expensive (OR: 5.27, 95% CI: 2.1-13.84, p = 0.001) at the first
      evaluation of patient's compliance were all predictors of NP.Among the 99 NP
      patients, 25 (25.3%) were recurrent-NP and accumulated more disease activity. The
      combination of both reasons of NP ("Because it was not available at the
      drugstore" and "Because the medication is very expensive") when selected at the
      first evaluation of compliance was the only variable to predict recurrent NP, OR:
      4.8, 95% CI: 1.1-20.8, p = 0.04. CONCLUSIONS: Health systems should provide
      (first line) treatment for RA as a strategy to improve compliance with therapy
      and clinical outcomes, particularly in vulnerable populations.

PMID- 24289730
TI  - Impact of audiovisual method in educating children facing dental avulsion.
AB  - INTRODUCTION: Dental trauma is a major problem in oral health in childhood
      especially if the result is a tooth avulsion. Subsequently, an appropriate
      management is essential to preserve the avulsed tooth. AIM: The goal of this
      study is to evaluate the knowledge of children concerning dental trauma and to
      highlight the importance of audio and visual methods in educating viewers in the
      management of such accident. MATERIALS AND METHODS: Three hundred and forty four
      children, aged between 8 and 11 years old, participated in this study. Half of
      them answered a questionnaire about the management of a tooth avulsion. Then,
      they watch an educational movie played by a speaker. Three months later, they
      answer the same questionnaire. The remaining 172 children are divided into two
      equal groups A and B. Group A watches the movie, and group B listens to the story
      and answers the same questionnaire. One more time, both groups watch the film and
      listen to its verbal interpretation, then both answer the same questionnaire
      again. The answers are analyzed. RESULTS: Before watching the movie, 4 of 172
      children answer correctly the question related to the conservation of the avulsed
      tooth. Three months after watching the movie, the correct answers increase to 52.
      For the second part of the study, after audiovisual information, the full score
      in group A increases from 20 to 58, and in group B from 49 to 67. CONCLUSION: The
      study highlights the importance of audiovisual method in transmitting an
      educational message and improving the knowledge of a large 'target audience'.

PMID- 24289731
TI  - Usability testing of ANSWER: a web-based methotrexate decision aid for patients
      with rheumatoid arthritis.
AB  - BACKGROUND: Decision aids are evidence-based tools designed to inform people of
      the potential benefit and harm of treatment options, clarify their preferences
      and provide a shared decision-making structure for discussion at a clinic visit.
      For patients with rheumatoid arthritis (RA) who are considering methotrexate, we
      have developed a web-based patient decision aid called the ANSWER (Animated, Self
      serve, Web-based Research Tool). This study aimed to: 1) assess the usability of
      the ANSWER prototype; 2) identify strengths and limitations of the ANSWER from
      the patient's perspective. METHODS: The ANSWER prototype consisted of: 1) six
      animated patient stories and narrated information on the evidence of methotrexate
      for RA; 2) interactive questionnaires to clarify patients' treatment preferences.
      Eligible participants for the usability test were patients with RA who had been
      prescribed methotrexate. They were asked to verbalize their thoughts (i.e., think
      aloud) while using the ANSWER, and to complete the System Usability Scale (SUS)
      to assess overall usability (range = 0-100; higher = more user friendly).
      Participants were audiotaped and observed, and field notes were taken. The
      testing continued until no new modifiable issues were found. We used descriptive
      statistics to summarize participant characteristics and the SUS scores. Content
      analysis was used to identified usability issues and navigation problems.
      RESULTS: 15 patients participated in the usability testing. The majority were
      aged 50 or over and were university/college graduates (n = 8, 53.4%). On average
      they took 56 minutes (SD = 34.8) to complete the tool. The mean SUS score was
      81.2 (SD = 13.5). Content analysis of audiotapes and field notes revealed four
      categories of modifiable usability issues: 1) information delivery (i.e., clarity
      of the information and presentation style); 2) navigation control (i.e.,
      difficulties in recognizing and using the navigation control buttons); 3) layout
      (i.e., position of the videos, text, diagrams and navigation buttons); 4)
      aesthetic (i.e., the colour, look and feel of the online tool). CONCLUSIONS:
      Although the SUS score indicated high usability before and after major
      modification, findings from the think-aloud sessions illustrated areas that
      required further refinement. Our results highlight the importance of formative
      evaluation in usability testing.

PMID- 24289732
TI  - Photochemical electronic doping of colloidal CdSe nanocrystals.
AB  - A method for electronic doping of colloidal CdSe nanocrystals (NCs) is reported.
      Anaerobic photoexcitation of CdSe NCs in the presence of a borohydride hole
      quencher, Li[Et3BH], yields colloidal n-type CdSe NCs possessing extra conduction
      band electrons compensated by cations deposited by the hydride hole quencher. The
      photodoped NCs possess excellent optical quality and display the key
      spectroscopic signatures associated with NC n-doping, including a bleach at the
      absorption edge, appearance of a new IR absorption band, and Auger quenching of
      the excitonic photoluminescence. Although stable under anaerobic conditions,
      these spectroscopic changes are all reversed completely upon exposure of the n
      doped NCs to air. Chemical titration of the added electrons confirms previous
      correlations between absorption bleach and electron accumulation and provides a
      means of quantifying the extent of electron trapping in some NCs. The generality
      of this photodoping method is demonstrated by initial results on colloidal CdE (E
      = S, Te) NCs as well as on CdSe quantum dot films. 

PMID- 24289733
TI  - The history of the elimination of lymphatic filariasis in China.
AB  - China used to be one of the most heavily endemic countries for lymphatic
      filariasis (LF) in the world. There were 864 endemic counties/cities in 16
      provinces/autonomous regions/municipalities (P/A/M) with a total population of
      330 million at risk of infection. Since the founding of the People's Republic of
      China in 1949, the Chinese Government has designated the control of the disease
      to be a top priority. Due to decades of sustained efforts, close cooperation
      related to LF control among government departments, and active participation of
      endemic populations, an all-round campaign for prevention and control has been
      carried out vigorously and successfully. Over many years, great achievements have
      been made through persistent endeavors of Chinese scientists and disease control
      workers. The ultimate goal to eliminate LF in the country was achieved in 2006. 

PMID- 24289734
TI  - Highchair philosophers: the impact of seating context-dependent exploration on
      children's naming biases.
AB  - We examine developmental interactions between context, exploration, and word
      learning. Infants show an understanding of how nonsolid substances are
      categorized that does not reliably transfer to learning how these categories are
      named in laboratory tasks. We argue that what infants learn about naming nonsolid
      substances is contextually bound - most nonsolids that toddlers are familiar with
      are foods and thus, typically experienced when sitting in a highchair. We asked
      whether 16-month-old children's naming of nonsolids would improve if they were
      tested in that typical context. Children tested in the highchair demonstrated
      better understanding of how nonsolids are named. Furthermore, context-based
      differences in exploration drove differences in the properties attended to in
      real-time. We discuss what implications this context-dependency has for
      understanding the development of an ontological distinction between solids and
      nonsolids. Together, these results demonstrate a developmental cascade between
      context, exploration, and word learning. 

PMID- 24289735
TI  - Sofosbuvir for the treatment of hepatitis C virus.
AB  - INTRODUCTION: The current treatment for hepatitis C virus (HCV) genotype 1
      chronic infection is the addition of direct-acting antivirals (DAAs) with a
      protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG
      IFN) and ribavirin (RBV) regimen. In 2014, sofosbuvir, simeprevir and faldaprevir
      may be available, each in combination with PEG-IFN/RBV triple therapy. All the
      HCV enzymes are essential for HCV replication, and are potential drug discovery
      targets. Therefore, DAAs with different viral targets, including NS3 protease
      inhibitors, nucleoside/nucleotide analogue and nonnucleoside inhibitors of the
      RNA-dependent RNA polymerase, and NS5A replication complex inhibitors are under
      development. AREAS COVERED: Interestingly, several IFN-free Phase III trials are
      ongoing with promising results. Among DAAs, sofosbuvir is a potent HCV-specific
      nucleotide analog (chain terminator). The aim of this article is to review
      sofosbuvir data, in particular Phase III trials. EXPERT OPINION: Sofosbuvir has a
      high barrier to resistance with no virologic breakthrough to date. It has a pan
      genotypic activity (even though lower rates of response for genotype 3). So far,
      no safety signal in preclinical/clinical studies has been observed with this
      compound. It is given orally, once daily, without food effect. Sofosbuvir will
      first be available in association with PEG-IFN/RBV. Sofosbuvir appears to be a
      key compound and a backbone for future IFN free treatment regimen.

PMID- 24289737
TI  - Audit of cholesterol management among primary care patients in rural southern
      Italy.
AB  - INTRODUCTION: There has not yet been an audit of achievement rates of therapeutic
      targets for cholesterol management in the rural Italian primary care setting. The
      purpose of this study was to measure the percentage of patients with
      hypercholesterolaemia in a rural primary care setting in southern Italy, classify
      their risk category and measure the proportions of those patients who achieved
      optimal cholesterol levels according to the Adult Treatment Panel III guidelines.
      METHODS: The audit was completed using records from 1 January 2005 to 31 December
      2007. An electronic search key was entered into the electronic clinical records
      of 10 family doctors in a rural area of southern Italy for subjects with a
      diagnosis of or being treated for hypercholesterolaemia. A total of 194
      hypercholesterolaemic patients were randomly selected from a cohort of patients
      registered with these family doctors. The low density lipoprotein cholesterol
      (LDL-C) target level was 100 mg/dL (2.6 mmol/L) in patients with existing
      cardiovascular disease, 130 mg/dL (3.3 mmol/L) for patients with &#8805;2 risk
      factors, and 160 mg/dL (4.1 mmol/L) for all other patients. The results regarding
      the efficacy of the therapy were categorised as follows: (1) on target, LDL-C
      lower or equal to levels of affiliated class; (2) poor control, 1-30 mg/dL (0.03
      0.78 mmol/L) above the target level of LDL-C; (3) very poor control, &#8805;31
      mg/dL (&#8805;0.8 mmol/L) above the LDL-C target level. RESULTS: The average age
      of the hypercholesterolaemic patients included in the study was 62.0 +/- 9.0
      years; 55% were males, 30% were smokers, 71.3% suffered from hypertension, 46.3%
      had diabetes, 39.9% were obese and 31.9% had a family history of coronary
      disease. There were 114 subjects in Class I (personal history of coronary
      disease, cardiovascular risk &#8805; 20, diabetes mellitus) LDL-C target level.
      Of these patients, 24.6% were at target, 30.7% had poor control and 44.7% had
      very poor control. A total of 42.3% of the subjects examined with the score
      system adopted by the Italian Heart Project showed levels of cardiovascular risk
      between 5% and 19% and were not eligible for a free prescription of lipid
      lowering drugs. CONCLUSIONS: These data suggest that cholesterol management in
      this rural area is not always optimal in patients with high cardiovascular risk.
      Italian healthcare regulation seems to be a barrier to drug prescription and it
      may influence optimal LDL-C control.

PMID- 24289736
TI  - A prospective, randomized, placebo-controlled, double-blind, multicenter study of
      the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial):
      study protocol.
AB  - BACKGROUND: Cardiovascular complications are the leading cause of mortality and
      morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by
      mutations in the gene that encodes fibrillin-1. There are approximately 18,000
      patients in the UK with MFS. Current treatment includes careful follow-up, beta
      blockers, and prophylactic surgical intervention; however, there is no known
      treatment which effectively prevents the rate of aortic dilatation in MFS.
      Preclinical, neonatal, and pediatric studies have indicated that angiotensin
      receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial
      will investigate the effects of irbesartan on aortic dilatation in Marfan
      syndrome. METHODS/DESIGN: The Aortic Irbesartan Marfan Study (AIMS) is an
      investigator-led, prospective, randomized, placebo-controlled, double-blind,
      phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490
      clinically confirmed MFS patients (aged >=6 to <=40 years) using the revised
      Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo.
      Aortic root dilatation will be measured by transthoracic echocardiography at
      baseline and annually thereafter. The primary outcome is the absolute change in
      aortic root diameter per year measured by echocardiography. The follow-up period
      will be a minimum of 36 months with an expected mean follow-up period of 48
      months. DISCUSSION: This is the first clinical trial to evaluate the ARB
      irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS.
      Not only will this provide useful information on the safety and efficacy of ARBs
      in MFS, it will also provide a rationale basis for potentially lifesaving therapy
      for MFS patients. TRIAL REGISTRATION: ISRCTN, 90011794.

PMID- 24289738
TI  - Evaluation of 6 years of confidential unit exclusion at the Belgian Red Cross
      Flanders Blood Service.
AB  - BACKGROUND AND OBJECTIVES: The effectiveness of the confidential unit exclusion
      (CUE) as a safety measure to the blood supply is debated. We therefore
      investigated the usefulness of CUE in our donor population. METHODS: Data of CUE
      use, donor deferrals due to different degrees of sexual or blood exposure and
      data of confirmed positive transfusion-transmissible infection (TTI) markers were
      analyzed for the study period January 1, 2004 to December 31, 2009. RESULTS: The
      CUE user tended to be of young age, male and first time donor whereas the CUE non
      responder was more likely to be older, first time donor without a clear sex
      predilection. CUE had low sensitivity (0.33%) and low positive predictive value
      (0.02%) in detecting TTI marker positive donations. Of 46 incident cases, one
      donor designated his pre-conversion donation as CUE positive. 29.6% of the donors
      deferred due to reported sex or intravenous drug related risk factors on the
      donor history questionnaire had ticked 'I do practice risk behavior' on the CUE
      form. Deferrals for all sexual or blood-blood contact related risk factors were
      19.2 times higher among CUE positive donors than among CUE negative donors (95%
      CI, 18.5-19.9). CONCLUSION: Although CUE use is associated with higher rates of
      TTI risk, CUE has low efficiency to detect window period donations. Moreover,
      misuse results in a significant loss of units. Our data indicate a low risk
      perception among donors, hence efforts should focus on improving donor knowledge
      of and on donor's responsibility to disclose TTI risk.

PMID- 24289739
TI  - Hyperosmotic response of streptococcus mutans: from microscopic physiology to
      transcriptomic profile.
AB  - BACKGROUND: Oral streptococci metabolize carbohydrate to produce organic acids,
      which not only decrease the environmental pH, but also increase osmolality of
      dental plaque fluid due to tooth demineralization and consequent calcium and
      phosphate accumulation. Despite these unfavorable environmental changes, the
      bacteria continue to thrive. The aim of this study was to obtain a global view on
      strategies taken by Streptococcus mutans to deal with physiologically relevant
      elevated osmolality, and perseveres within a cariogenic dental plaque. RESULTS:
      We investigated phenotypic change of S. mutans biofilm upon hyperosmotic
      challenge. We found that the hyperosmotic condition was able to initiate S.
      mutans biofilm dispersal by reducing both microbial content and extracellular
      polysaccharides matrix. We then used whole-genome microarray with quantitative RT
      PCR validation to systemically investigate the underlying molecular machineries
      of this bacterium in response to the hyperosmotic stimuli. Among those identified
      40 deferentially regulated genes, down-regulation of gtfB and comC were believed
      to be responsible for the observed biofilm dispersal. Further analysis of
      microarray data showed significant up-regulation of genes and pathways involved
      in carbohydrate metabolism. Specific genes involved in heat shock response and
      acid tolerance were also upregulated, indicating potential cross-talk between
      hyperosmotic and other environmental stress. CONCLUSIONS: Hyperosmotic condition
      induces significant stress response on S. mutans at both phenotypic and
      transcriptomic levels. In the meantime, it may take full advantage of these
      environmental stimuli to better fit the fluctuating environments within oral
      cavity, and thus emerges as numeric-predominant bacterium under cariogenic
      conditions.

PMID- 24289741
TI  - Bone marrow edema syndrome of the hip: analysis of 10 cases.

PMID- 24289740
TI  - Cluster randomized controlled trial of a psycho-educational intervention for
      people with a family history of depression for use in general practice.
AB  - BACKGROUND: The strongest risk factor for depression is having a family history
      of the condition. Many individuals with a family history of depression are
      concerned about their personal risk for depression and report unmet educational
      and psychological support needs. No supportive and/or educational interventions
      are currently available that target this group of individuals. In this study we
      will develop and evaluate the first online psycho-educational intervention
      targeted to individuals with a family history of depression. Genetic risk
      information and evidence-rated information on preventive strategies for
      depression will be provided to such individuals in a general practice setting.
      The intervention will also incorporate a risk assessment tool. The content and
      delivery of the intervention will be pilot-tested. METHODS/DESIGN: The proposed
      intervention will be evaluated in the general practitioner (GPs) setting, using a
      cluster randomized controlled trial. GP practices will be randomized to provide
      either access to the online, targeted psycho-educational intervention or brief
      generic information about depression (control) to eligible patients. Eligibility
      criteria include having at least one first-degree relative with either major
      depressive disorder (MDD) or bipolar disorder (BD). The primary outcome measure
      is 'intention to adopt, or actual adoption of, risk-reducing strategies'.
      Secondary outcome measures include: depression symptoms, perceived stigma of
      depression, knowledge of risk factors for development of depression and risk
      reducing strategies, and perceived risk of developing depression or having a
      recurrence of family history. Over the course of the study, participants will
      complete online questionnaires at three time points: at baseline, and two weeks
      and six months after receiving the intervention or control condition. DISCUSSION:
      This novel psycho-educational intervention will provide individuals with a family
      history of depression with information on evidence-based strategies for the
      prevention of depression, thus, we hypothesize, enabling them to make appropriate
      lifestyle choices and implement behaviors designed to reduce their risk for
      depression. The online psycho-educational intervention will also provide a model
      for similar interventions aimed at individuals at increased familial risk for
      other psychiatric disorders. TRIAL REGISTRATION: The study is registered with the
      Australian and New Zealand Clinical Trials Group (Registration no:
      ACTRN12613000402741).

PMID- 24289742
TI  - Transcription factors spt3 and spt8 are associated with conidiation, mycelium
      growth, and pathogenicity in Fusarium graminearum.
AB  - Fusarium graminearum (teleomorph: Gibberella zeae), the dominant pathogen of
      Fusarium head blight (FHB) on wheat, can cause substantial economic losses. The
      Spt-Ada-Gcn5-acetyltransferase (SAGA) transcription coactivator plays multiple
      roles in regulating transcription because of the presence of functionally
      independent modules of subunits within the complex. The transcription factors
      spt3 and spt8 are components of the SAGA complex and they are important in yeasts
      and filamentous fungi including F. graminearum. In this study, we identified
      Fgspt3 and Fgspt8, homologs of Saccharomyces cerevisiae spt3 and spt8 from F.
      graminearum using the blastp program. The aim of the present study was to
      investigate the functions of Fgspt3 and Fgspt8 in F. graminearum. The deletion
      mutants grew significantly more slowly than the wild-type parent and did not
      produce conidia. Expression of the sporulation-related genes FgFlbC and FgRen1
      were significantly down-regulated in the mutants. The mutants exhibited no sexual
      reproduction on infected wheat kernels and a 90% decrease in virulence on wheat.
      Pigment formation was also greatly altered in the mutants. All of the defects
      were restored by genetic complementation of the mutant with wild-type Fgspt3 and
      Fgspt8 genes. Overall, Fgspt3 and Fgspt8 are essential genes in F. graminearum.

PMID- 24289743
TI  - Nitrite activation to nitric oxide via one-fold protonation of iron(II)-O,O
      nitrito complex: relevance to the nitrite reductase activity of deoxyhemoglobin
      and deoxyhemerythrin.
AB  - The reversible transformations [(Bim)3Fe(kappa(2)-O2N)][BF4] (3) <->
      [(Bim)3Fe(NO)(kappa(1)-ONO)][BF4]2 (4) were demonstrated and characterized.
      Transformation of O,O-nitrito-containing complex 3 into [(Bim)3Fe(MU-O)(MU
      OAc)Fe(Bim)3](3+) (5) along with the release of NO and H2O triggered by 1 equiv
      of AcOH implicates that nitrite-to-nitric oxide conversion occurs, in contrast to
      two protons needed to trigger nitrite reduction producing NO observed in the
      protonation of [Fe(II)-nitro] complexes.

PMID- 24289745
TI  - Progressive alveolar echinococcosis after discontinuation of anthelmintic
      therapy.
AB  - We report a case of a female patient with alveolar echinococcosis (AE) who
      presented with progressive pulmonary and hepatic lesions and had a fatal outcome.
      AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago
      and treated successfully with albendazole and stereotactic gamma knife therapy.
      Due to severe hair loss albendazole was stopped 14 years before presentation.
      Lesions had remained stable in imaging studies for at least 11 years, but then
      had started to progress. Lifelong anthelmintic maintenance therapy and regular
      follow-up may therefore be crucial in order to prevent such a dramatic clinical
      course. 

PMID- 24289744
TI  - Glycophenotyping of osteoarthritic cartilage and chondrocytes by RT-qPCR, mass
      spectrometry, histochemistry with plant/human lectins and lectin localization
      with a glycoprotein.
AB  - INTRODUCTION: This study aimed to characterize the glycophenotype of
      osteoarthritic cartilage and human chondrocytes. METHODS: Articular knee
      cartilage was obtained from nine osteoarthritis (OA) patients. mRNA levels for 27
      glycosyltransferases were analyzed in OA chondrocytes using RT-qPCR.
      Additionally, N- and O-glycans were quantified using mass-spectrometry.
      Histologically, two cartilage areas with Mankin scores (MS) either <= 4 or >= 9
      were selected from each patient representing areas of mild and severe OA,
      respectively. Tissue sections were stained with (1) a selected panel of plant
      lectins for probing into the OA glycophenotype, (2) the human lectins galectins-1
      and -3, and (3) the glycoprotein asialofetuin (ASF) for visualizing beta
      galactoside-specific endogenous lectins. RESULTS: We found that OA chondrocytes
      expressed oligomannosidic structures as well as non-, mono- and disialylated
      complex-type N-glycans, and core 2 O-glycans. Reflecting B4GALNT3 mRNA presence
      in OA chondrocytes, LacdiNAc-terminated structures were detected. Staining
      profiles for plant and human lectins were dependent on the grade of cartilage
      degeneration, and ASF-positive cells were observed in significantly higher rates
      in areas of severe degeneration. CONCLUSIONS: In summary, distinct aspects of the
      glycome in OA cartilage are altered with progressing degeneration. In particular,
      the alterations measured by galectin-3 and the pan-galectin sensor ASF encourage
      detailed studies of galectin functionality in OA.

PMID- 24289746
TI  - Indoxyl sulfate promotes apoptosis in cultured osteoblast cells.
AB  - BACKGROUND: Indoxyl sulfate (IS), an organic anion uremic toxin, promotes the
      progression of renal dysfunction. Some studies have suggested that IS inhibits
      osteoclast differentiation and suppresses parathyroid hormone (PTH)-stimulated
      intracellular cAMP production, decreases PTH receptor expression, and induces
      oxidative stress in primary mouse calvaria osteoblast cell culture. However, the
      direct effects of IS on osteoblast apoptosis have not been fully evaluated.
      Hence, we investigated whether IS acts as a bone toxin by studying whether IS
      induces apoptosis and inhibits differentiation in the cultured osteoblast cell
      line MC3T3-E1. METHODS: We assessed the direct effect of IS on osteoblast
      differentiation and apoptosis in the MC3T3-E1 cell line. We examined caspase-3/7
      activity, apoptosis-related proteins, free radical production, alkaline
      phosphatase activity, and mRNA expression of type 1 collagen and osteonectin.
      Furthermore, we investigated the uptake of IS via organic anion transport (OAT).
      RESULTS: We found that IS increased caspase activity and induced apoptosis.
      Production of free radicals increased depending on the concentration of IS.
      Furthermore, IS inhibited the expression of mRNA type 1 collagen and osteonectin
      and alkaline phosphatase activity. The expression of OAT, which is known to
      mediate the cellular uptake of IS, was detected in in the MC3T3-E1 cell line. The
      inhibition of OAT improved cell viability and suppressed the production of
      reactive oxygen species. These results suggest that IS is transported in MC3T3-E1
      cells via OAT, which causes oxidative stress to inhibit osteoblast
      differentiation. CONCLUSIONS: IS acts as a bone toxin by inhibiting osteoblast
      differentiation and inducing apoptosis.

PMID- 24289747
TI  - Access to the US Department of Veterans Affairs health system: self-reported
      barriers to care among returnees of Operations Enduring Freedom and Iraqi
      Freedom.
AB  - BACKGROUND: The U.S. Department of Veterans Affairs (VA) implemented the
      Polytrauma System of Care to meet the health care needs of military and veterans
      with multiple injuries returning from combat operations in Afghanistan and Iraq.
      Studies are needed to systematically assess barriers to use of comprehensive and
      exclusive VA healthcare services from the perspective of veterans with polytrauma
      and with other complex health outcomes following their service in Afghanistan and
      Iraq. These perspectives can inform policy with regard to the optimal delivery of
      care to returning veterans. METHODS: We studied combat veterans (n = 359) from
      two polytrauma rehabilitation centers using structured clinical interviews and
      qualitative open-ended questions, augmented with data collected from electronic
      health records. Our outcomes included several measures of exclusive utilization
      of VA care with our primary exposure as reported access barriers to care.
      RESULTS: Nearly two thirds of the veterans reported one or more barriers to their
      exclusive use of VA healthcare services. These barriers predicted differences in
      exclusive use of VA healthcare services. Experiencing any barriers doubled the
      returnees' odds of not using VA exclusively, the geographic distance to VA
      barrier resulted in a 7 fold increase in the returnees odds of not using VA, and
      reporting a wait time barrier doubled the returnee's odds of not using VA. There
      were no striking differences in access barriers for veterans with polytrauma
      compared to other returning veterans, suggesting the barriers may be uniform
      barriers that predict differences in using the VA exclusively for health care.
      CONCLUSIONS: This study provides an initial description of utilization of VA
      polytrauma rehabilitation and other medical care for veteran returnees from all
      military services who were involved in combat operations in Afghanistan or Iraq.
      Our findings indicate that these veterans reported important stigmatization and
      barriers to receiving services exclusively from the VA, including mutable health
      delivery system factors.

PMID- 24289748
TI  - Does the revised cardiac risk index predict cardiac complications following
      elective lung resection?
AB  - BACKGROUND: Revised Cardiac Risk Index (RCRI) score and Thoracic Revised Cardiac
      Risk Index (ThRCRI) score were developed to predict the risks of postoperative
      major cardiac complications in generic surgical population and thoracic surgery
      respectively. This study aims to determine the accuracy of these scores in
      predicting the risk of developing cardiac complications including atrial
      arrhythmias after lung resection surgery in adults. METHODS: We studied 703
      patients undergoing lung resection surgery in a tertiary thoracic surgery centre.
      Observed outcome measures of postoperative cardiac morbidity and mortality were
      compared against those predicted by risk. RESULTS: Postoperative major cardiac
      complications and supraventricular arrhythmias occurred in 4.8% of patients. Both
      index scores had poor discriminative ability for predicting postoperative cardiac
      complications with an area under receiver operating characteristic (ROC) curve of
      0.59 (95% CI 0.51-0.67) for the RCRI score and 0.57 (95% CI 0.49-0.66) for the
      ThRCRI score. CONCLUSIONS: In our cohort, RCRI and ThRCRI scores failed to
      accurately predict the risk of cardiac complications in patients undergoing
      elective resection of lung cancer. The British Thoracic Society (BTS)
      recommendation to seek a cardiology referral for all asymptomatic pre-operative
      lung resection patients with > 3 RCRI risk factors is thus unlikely to be of
      clinical benefit.

PMID- 24289749
TI  - The effect of cervical cerclage on pregnancy outcomes in women following
      conization.
AB  - OBJECTIVES: To determine the effect of cervical cerclage on obstetrical
      complications and perinatal outcomes of patients following conization. DESIGN: A
      retrospective population based cohort study. SETTING: Tertiary academic medical
      center that covers all the deliveries of the region. POPULATION: All patients
      with previous cervical conization who delivered between the years 1994-2011.
      METHODS: A retrospective population based study. MAIN OUTCOME MEASURES: The
      effect of cerclage placement on the rate of preterm birth. RESULTS: During the
      study period there were 109 deliveries of patients following a cervical
      conization. Cervical cerclage was placed in 22 deliveries that served as the
      study group and the rest (n = 87) served as the comparison group. The rate of
      early preterm delivery (PTD;  <34 weeks) was significantly higher in women who
      had a cerclage. In a logistic regression model, cerclage was found to be an
      independent risk factor for early PTD. CONCLUSION: Cerclage is an independent
      risk factor for early PTD In patients who had a conization due to CIN.

PMID- 24289750
TI  - Varicella zoster: an update on current treatment options and future perspectives.
AB  - INTRODUCTION: Varicella zoster virus is a highly contagious virus that causes a
      primary infection known as varicella (chickenpox) that may reactivate years later
      to cause herpes zoster (HZ or shingles). After shingles heal, patients may
      develop post-herpetic neuralgia (PHN), neuropathic pain syndrome that can cause
      significant suffering for years and is often refractory to treatment. AREAS
      COVERED: The wide range of treatment and management options for varicella, HZ and
      PHN are reviewed and discussed. PubMed was the database used for the literature
      search. EXPERT OPINION: Antiviral therapy effectively treats acute varicella and
      HZ. However, PHN is still difficult to manage, especially with the numerous
      treatment measures that do not work consistently in all patients. The best
      approach is to prevent the complication from occurring in the first place by
      preventing HZ with the HZ vaccine, which have decreased the burden of illness
      caused by VZ and the incidence of HZ. Unlike the varicella vaccine, the uptake
      for the HZ vaccine is very low and thereby more patients over the age of 50 years
      should be encouraged to receive the vaccine to reduce the risk of developing HZ.
      Initiating treatment with gabapentin and antiviral concomitantly as soon as the
      rash develops may reduce the severity of complications but there is a lack of
      data showing these medications preventing the development of PHN.

PMID- 24289751
TI  - A community-based intervention for primary prevention of cardiovascular diseases
      in the slums of Nairobi: the SCALE UP study protocol for a prospective quasi
      experimental community-based trial.
AB  - BACKGROUND: The burden of cardiovascular disease is rising in sub-Saharan Africa
      with hypertension being the main risk factor. However, context-specific evidence
      on effective interventions for primary prevention of cardiovascular diseases in
      resource-poor settings is limited. This study aims to evaluate the feasibility
      and cost-effectiveness of one such intervention--the "Sustainable model for
      cardiovascular health by adjusting lifestyle and treatment with economic
      perspective in settings of urban poverty". METHODS/DESIGN:  DESIGN: A prospective
      quasi-experimental community-based intervention study. SETTING: Two slum
      settlements (Korogocho and Viwandani) in Nairobi, Kenya. STUDY POPULATION: Adults
      aged 35 years and above in the two communities. INTERVENTION: The intervention
      community (Korogocho) will be exposed to an intervention package for primary
      prevention of cardiovascular disease that comprises awareness campaigns,
      household screening for cardiovascular diseases risk factors, and referral and
      treatment of people with high cardiovascular diseases risk at a primary health
      clinic. The control community (Viwandani) will continue accessing the usual
      standard of care for primary prevention of cardiovascular diseases in Kenya.
      DATA: Demographic and socioeconomic data; anthropometric and clinical
      measurements including blood pressure. Population-based data will be collected at
      the baseline and endline--12 months after implementing the intervention. These
      data will be collected from a random sample of 1,610 adults aged 35 years and
      above in the intervention and control sites at both baseline and endline.
      Additionally, operational (including cost) and clinic-based data will be
      collected on an ongoing basis. MAIN OUTCOMES: (1) A positive difference in the
      change in the proportion of the intervention versus control study populations
      that are at moderate or high risk of cardiovascular disease; (2) a difference in
      the change in mean systolic blood pressure in the intervention versus control
      study populations; (3) the net cost of the complete intervention package per
      disability-adjusted life year gained. ANALYSIS: Primary outcomes comparing pre-
      and post-, and operational data will be analyzed descriptively and "impact" of
      the intervention will be calculated using double-difference methods. We will also
      conduct a cost-effectiveness analysis of the intervention using World Health
      Organization guidelines. DISCUSSION: The outcomes of the study will be
      disseminated to local policy makers and health planners. TRIAL REGISTRATION:
      Current controlled trials ISRCTN84424579.

PMID- 24289752
TI  - Traumatic dental injury in permanent teeth of young patients attended at the
      federal University of Rio de Janeiro, Brazil.
AB  - BACKGROUND/AIM: Risk factors for dental trauma, such as gender and age, have not
      been studied in much detail in the past. So, this study was to determine the
      frequency of Traumatic dental injuries (TDI) and the association of gender and
      age with the different types of injuries in permanent teeth of patients treated
      at the Dental Trauma Surveillance Center, Federal University of Rio de Janeiro,
      Brazil. MATERIAL AND METHODS: Data from records of 1022 patients were evaluated,
      and patients with TDI in permanent teeth were included and descriptively
      analyzed. The Chi-squared test and logistic regression were also used (P <=
      0.05). RESULTS: A total of 352 (34.4%) records from patients (mean age 9.29 +/-
      1.97) with 676 affected permanent teeth were included in the final sample.
      Children (55.7%) have a higher frequency of TDI than adolescents (42.9%). Falls
      (54.3%) was the most common cause, and the street (37.5%) was the most frequent
      place of occurrence. Enamel and dentin fracture without pulp exposure (69.2%) was
      the most common TDI for both genders (P = 0.16). Avulsion (29.2%) was the most
      frequent injury to supportive tissues for both genders; however, this was more
      numerous in girls (P < 0.001). Intrusive luxation was more common in boys (P =
      0.01). According to logistic regression, intrusive luxation affects girls less
      (OR = 0.394; IC = 0.178-0.875) than boys, while girls have more chance of
      suffering from avulsion (OR = 1.912; IC = 1.197-3.055) and avulsion was less
      frequent in children (OR = 0.588; IC = 0.373-0.928). CONCLUSIONS: Enamel and
      dentin fractures without pulp exposure and avulsion were the most common TDI.
      Gender (female) and age (adolescent) were considered risk factors for the
      occurrence of avulsion. However, male gender was a risk factor for the occurrence
      of intrusive luxation. So public health policies and educational programs aimed
      at prevention need to be developed, and the differences among groups should be
      respected.

PMID- 24289753
TI  - Penile size in healthy Nigerian newborns: country-based reference values and
      international comparisons.
AB  - AIM: To establish normal reference values for penile size in Nigerian newborn
      boys and to compare those values with standards from other populations. METHODS:
      A total number of 261 healthy newborn boys delivered at gestational ages of 28
      weeks or more were enrolled in the study. Penile lengths and widths were measured
      within 72 h of birth. RESULTS: The mean (+/-SD) penile length in the 261 Nigerian
      males studied was 3.4 +/- 0.48 cm, while the mean mid-shaft diameter was 1.2 +/-
      0.14 cm. Compared with data from other populations, Nigerian newborn boys had
      similar penile sizes to those reported for US Caucasian boys (mean 3.4 cm), but
      significantly greater penile sizes than those reported for boys from China and
      Hong Kong (mean 3.0 and 3.1 cm, respectively; both p < 0.001). There was a
      slight, but significant, difference in size between Nigerian and Malaysian boys,
      with Malaysian boys having greater penile sizes (mean 3.5 cm; p < 0.05).
      CONCLUSION: A Nigerian newborn with a penile length of <2.39 cm can be considered
      to have a micropenis.

PMID- 24289754
TI  - Self-determination and older people--a concept analysis.
AB  - BACKGROUND: Self-determination has emerged as an important concept within health
      care, used to emphasize clients' control and independence as they participate in
      rehabilitation. To strengthen clients' self-determination is a central aim in
      occupational therapy. However, there is a lack of a clear definition of self
      determination concerning community-dwelling older people. The definition should
      be flexible in different contexts, such as cultural. OBJECTIVE: To define and
      clarify the concept of self-determination in relation to community-dwelling frail
      older people. METHOD: Walker & Avant's analysis procedure was carried out to
      identify textual attributes to the concept of self-determination, supplemented by
      a content analysis of 21 articles that were used to define and further justify
      the textual attributes. RESULTS: Self-determination was used in diverse contexts
      for community-dwelling older people, concerning: decision-making in everyday
      life, professionals' views, health, and legal/ethical rights. Different textual
      attributes were identified, to propose a conceptual definition of self
      determination in relation to community-dwelling frail older people: A process in
      which a person has control and legal/ethical rights, and has the knowledge and
      ability to make a decision of his/her own free choice. PRINCIPAL CONCLUSION: This
      concept analysis has contributed to clarifying the concept for the convenience of
      research with community-dwelling frail older people.

PMID- 24289755
TI  - Morphological aspects of myocardial bridges.
AB  - Although some myocardial bridges can be asymptomatic, their presence often causes
      coronary disease either through direct compression of the "tunnel" segment or
      through stimulation and accelerated development of atherosclerosis in the segment
      proximally to the myocardial bridge. The studied material contained 30 human
      hearts received from the Department of Anatomy. The hearts were preserved 3 to 5
      days in 10% formalin solution. Thereafter, the fatty tissue was removed and
      arterial blood vessels prepared by careful dissection with special reference to
      the presence of the myocardial bridges. Length and thickness of the bridges were
      measured by the precise electronic caliper. The angle between the myocardial
      bridge fibre axis and other axis of the crossed blood vessel was measured by a
      goniometer. The presence of the bridges was confirmed in 53.33% of the researched
      material, most frequently (43.33%) above the anterior interventricular branch.
      The mean length of the bridges was 14.64 +/- 9.03 mm and the mean thickness was
      1.23 +/- 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel
      at the angle of 10-90 degrees. The results obtained on a limited sample suggest
      that the muscular index of myocardial bridge is the highest for bridges located
      on RIA, but that the difference is not significant in relation to bridges located
      on other branches. The results obtained suggest that bridges located on other
      branches, not only those on RIA, could have a great contractive power and,
      consequently, a great compressive force, which would be exerted on the wall of a
      crossed blood vessel.

PMID- 24289756
TI  - The protective effect of diosmin on hepatic ischemia reperfusion injury: an
      experimental study.
AB  - Liver ischemia reperfusion injury (IRI) is an important pathologic process
      leading to bodily systemic effects and liver injury. Our study aimed to
      investigate the protective effects of diosmin, a phlebotrophic drug with
      antioxidant and anti-inflammatory effects, in a liver IRI model. Forty rats were
      divided into 4 groups. Sham group, control group (ischemia-reperfusion),
      intraoperative treatment group, and preoperative treatment group. Ischemia
      reperfusion model was formed by clamping hepatic pedicle for a 60 minute of
      ischemia followed by liver reperfusion for another 90 minutes. Superoxide
      dismutase (SOD) and catalase (CAT) were measured as antioaxidant enzymes in the
      liver tissues, and malondialdehyde (MDA) as oxidative stress marker, xanthine
      oxidase (XO) as an oxidant enzyme and glutathione peroxidase (GSH-Px) as
      antioaxidant enzyme were measured in the liver tissues and the plasma samples.
      Hepatic function tests were lower in treatment groups than control group (p<0.001
      for ALT and AST). Plasma XO and MDA levels were lower in treatment groups than
      control group, but plasma GSH-Px levels were higher (p<0.05 for all). Tissue MDA
      levels were lower in treatment groups than control group, but tissue GSH-Px, SOD,
      CAT and XO levels were higher (p<0.05 for MDA and p<0.001 for others). Samples in
      control group histopathologically showed morphologic abnormalities specific to
      ischemia reperfusion. It has been found that both preoperative and intraoperative
      diosmin treatment decreases cellular damage and protects cells from toxic effects
      in liver IRI. As a conclusion, diosmin may be used as a protective agent against
      IRI in elective and emergent liver surgical operations.

PMID- 24289757
TI  - B-type natriuretic peptide and adiponectin releases in rat model of myocardial
      damage induced by isoproterenol administration.
AB  - B-type natriuretic peptide (BNP) and adiponectin play important role in the
      cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum
      levels followed by isoproterenol (ISO) administration to rats and explored the
      relationship between them. Cardiac troponin I (cTnI) blood level was used as
      biochemical evidence of myocardial damage development. Adult male Wistar rats
      (average body weight 273.33 +/- 21.63 g) were distributed into groups: control
      group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous
      single dose 100 mg/kg of rat body weight). ISO group was divided into two groups
      according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2
      hours after ISO administration); ISO II (n=6; 4 hours after ISO administration).
      Blood for determination of parameters was taken from rat abdominal aorta. BNP,
      adiponectin and cTnI were determined by ELISA method. Data were statistically
      analysed by using SPSS version 13 computer program. P value less 0.05 was
      considered statistically significant. Blood BNP and adiponectin were lower at 2
      hours after ISO administration in comparison with control group (p=0.004 for BNP
      and p=0.174 for adiponectin). Four hours after ISO administration, we have noted
      significant elevation of both parameters compared to ISO I group (p=0.004 for
      BNP; p=0.02 for adiponectin). Test of correlation have showed significant
      relation between their blood levels during experimental period (rho=0.577;
      p=0.01). BNP and adiponectin are not simple indicators of myocardial damage
      development. They have possible associated and additive effects in cardiovascular
      homeostasis regulation.

PMID- 24289758
TI  - Immunoregulatory cytokines and chronic tonsillitis.
AB  - The purposes of the present study were to determine the distribution of cells
      producing cytokines: tumor necrosis factor alpha (TNF-alpha) and interleukin 6
      (IL-6) in different morphological sections of tonsils in patients with tonsillar
      hypertrophy (TH) and recurrent tonsillitis (RT), to analyze the level of
      production of these cytokines in TH and RT and evaluate the potential of
      peripheral blood lymphocytes for production of interferon-gamma (IFN-gamma) and
      interleukin 4 (IL-4). Analyzed materials consisted of the tonsils after
      tonsillectomy and blood taken from patients right before tonsillectomy (study
      group) and blood taken from healthy donors (control group).We used histological
      and immunohistochemical method, morphometric methods for the quantification of
      TNF-alpha and IL- 6 producing cells and immunological methods for determining the
      concentration of IFN-gamma and IL-4. Most of TNF-alpha producing cells are
      settled in the subepithelial region (55%). Numerical density of TNF-alpha
      producing cells in the crypt epithelium, subepithelial and interfollicular region
      was significantly higher in RT compared with TH. The concentration of IFN-gamma
      is three times higher in RT then in TH. After the stimulation of peripheral blood
      lymphocytes in culture there was no significant increase in concentrations of IL-
      4. The index of stimulation of IFN-gamma was the highest in the RT, and of IL- 4
      in TH. The production of Th1-type cytokines (TNF-alpha and IFN-gamma) is higher
      in RT compared with TH. In both forms of tonsillitis, production of Th1-type
      cytokines is higher in relation to the production of Th2-type cytokines (IL-6 and
      IL-4). 

PMID- 24289759
TI  - Morphometric measurements of the cranium in congenital bilateral blind males and
      females.
AB  - Cranium dimensions differ according to racial, geopraphic, ethnic and nutritional
      factors. This study will shed light on the question: "Is there a difference in
      the cranial distances measured between congenital bilateral blind people and
      healthy individuals?" Nine anthropometric measures were performed on the brain
      MRI midsagittally obtained from male and female congenital bilateral blinds. The
      anthropometric measures taken included the glabella-opisthocranion, nasion-dorsum
      sellae, dorsum sellae- opisthocranion, nasion-basion, nasion-opisthion, basion
      opisthion, prosthion-basion, basion-vertex and the clival angle. In addition, the
      supratentorial and infratentorial areas were calculated. Glabella-opisthocranion,
      nasion-dorsum sellae, nasion-basion, prosthion-basion and clival angle were found
      to be smaller in the congenital bilateral blind females compared to the healthy
      group, but these results were not statistically significant. Whereas, other
      measures out of the basion-opisthion were found to be smaller in the congenital
      bilateral blind males than in the healthy subjects. Of these results, the
      distance between glabella-opisthocranion, nasion-dorsum sellae and nasion-basion
      was significantly smaller compared to the measurements taken from the healthy
      male group. The infratentorial area was significantly smaller in congenital blind
      male subjects and the supratentorial area was significantly larger in congenital
      blind female subjects. This study has revealed that the cranium dimensions of
      congenital blind people are to different from normal individuals. The most
      significant difference was in the distance of the nasion-dorsum sellae. The
      region anterior to the basion and dorsum sellae was prominently smaller. The
      infratentorial area was significantly smaller in congenital blind male subjects
      and the supratentorial area was significantly larger in congenital blind female
      subjects.

PMID- 24289760
TI  - Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH,
      and NO in a rat model of pentylenetetrazole-induced epileptic seizure.
AB  - Epilepsy is one of the most common neurological disorders, characterized by
      recurrent seizures, which may increase the content of reactive oxygen and
      nitrogen species. The objective of this study was to investigate the effects of
      Neuropeptide Y on oxidative and nitrosative balance and brain-derived
      neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant
      drug) in the hippocampus of Wistar rats. Three groups of seven rats were treated
      intraperitoneally as follows: group 1 (saline + saline) 1 ml saline, group 2
      (salin + Pentylenetetrazole) 1 ml saline 30 min before Pentylenetetrazole; and
      group 3 (Neuropeptide Y + Pentylenetetrazole) 60 MUg/kg Neuropeptide Y 30 min
      before 60 mg/kg Pentylenetetrazole. After 24 h, the animals were euthanized by
      decapitation. Hippocampus were isolated to evaluate the malondialdehyde,
      glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three
      rat groups. The results of this study demonstrated that while intraperitoneally
      administered neuropeptide Y did not result in a statistically significant
      difference in BDNF levels, its administration caused a statistically significant
      decrease in malondialdehyde and nitric oxide levels and an increase in
      glutathione levels in rats with pentylenetetrazole-induced epileptic seizure.
      Neuropeptide Y were able to reduce nitroxidative damage induced by
      pentylenetetrazole in the hippocampus of Wistar rats.

PMID- 24289761
TI  - Sexual function improvement in association with serum leptin level elevation in
      patients with premature ejaculation following sertraline treatment: a preliminary
      observation.
AB  - The objective of our work was to evaluate the effect of sertraline hydrochloride
      on serum levels of leptin and sexual function in patients with premature
      ejaculation (PE). A total of 124 patients with a history of PE at least 6 months,
      aged 20-50 years, were treated with sertraline hydrochloride. One hundred and
      four age-matched normal males without a history of PE were included control
      subjects and were untreated. Before and after the 8 week experiment, sexual
      performance parameters including the intravaginal ejaculation latency time (IELT)
      and the Chinese premature ejaculation index (CIPE) were collected from both PE
      patients and control subjects through a questionnaire survey and analyzed. Serum
      levels of leptin were measured. Correlations of serum leptin with Body Mass Index
      (BMI) were analyzed. Before sertraline treatment, serum levels of leptin were
      significantly higher (32.9 vs 8.8 MUg/L, p<0.001) but IELT and CIPE score were
      significantly lower (54 vs 590, p <0.001; 8.7 vs 22.3, p <0.0001) in PE patients
      than control subjects. After 8 weeks of treatment with sertraline, serum levels
      of leptinl in PE patients were decreased markedly to 8.0 MUg/L, which was not
      significantly different from the levels in control subjects (p >0.05); and IELT
      and CIPE score in PE patients were increased to the values similar to those in
      control subjects. The sensitivity and specificity values were 87.5% and 96.3% for
      leptin as a diagnosis target. These observations suggest sertraline as a
      selective serotonin reuptake inhibitor may offer an effective option for treating
      premature ejaculation.

PMID- 24289762
TI  - Assessment of the consistency among three drug compendia in listing and ranking
      of drug-drug interactions.
AB  - Inconsistent information about drug-drug interactions can cause variations in
      prescribing, and possibly increase the incidence of morbidity and mortality. The
      aim of this study was to assess whether there is an inconsistency in drug-drug
      interaction listing and ranking in three authoritative, freely accessible online
      drug information sources: The British National Formulary; The Compendium about
      Drugs Licensed for Use in the United Kingdom (the Electronic Medicines
      Compendium) and the Compendium about Drugs Licensed for Use in the United States
      (the DailyMed). Information on drug-drug interactions for thirty drugs which have
      a high or medium potential for interactions have been selected for analysis. In
      total, 1971 drug-drug interactions were listed in all three drug information
      sources, of these 992 were ranked as the interactions with the potential of
      clinical significance. Comparative analysis identified that 63.98% of
      interactions were listed in only one drug information source, and 66.63% of
      interactions were ranked in only one drug information source. Only 15.12% listed
      and 11.19% ranked interactions were identified in all three information sources.
      Intraclass correlation coefficient indicated a weak correlation among the three
      drug information sources in listing (0.366), as well as in ranking drug
      interactions (0.467). This study showed inconsistency of information on drug-drug
      interaction for the selected drugs in three authoritative, freely accessible
      online drug information sources. The application of a uniform methodology in
      assessment of information, and then the presentation of information in a
      standardized format is required to prevent and adequately manage drug-drug
      interactions.

PMID- 24289763
TI  - The utility of procollagen type 1 N-terminal propeptide for the bone status
      assessment in postmenopausal women.
AB  - The utility of procollagen type 1 N-terminal propeptide (P1NP) in the management
      of metabolic bone diseases remains a subject of debate since the reference ranges
      are not rigorously established and fail to account for many of the preanalytical
      variables. We aimed to establish reference intervals for P1NP level in healthy
      and osteoporotic postmenopausal females stratified by age, body mass index and
      menopausal duration. We also aimed to assess the relationship between P1NP and
      BMD. This cross-sectional study enrolled 183 postmenopausal females who were
      divided in osteoporosis group (N=93) and control group (N=90) with preserved bone
      mass based on BMD assessed by DXA. In the osteoporosis group median P1NP was
      significantly higher (51.7 ng / mL; 95%CI 43.2-53.7) compared to control group
      (38.9 ng/mL; 95%CI 34.2-43.9)(p<0.01). After controlling for age, BMI and years
      since menopause, there was significant inverse association between BMD and P1NP
      at the femoral neck (r=-0.18), total hip (r=-0.207) and lumbar spine (r=-0.236).
      There was no significant difference in P1NP concentration across quartiles of age
      in postmenopausal females. P1NP was significantly lower in obese postmenopausal
      females with preserved bone mass compared to normal weight and overweight females
      in control and in osteoporosis group. In conclusion, we showed that P1NP is
      inversely associated with BMD even after controlling for age, BMI and years since
      menopause. Although, P1NP is significantly higher in postmenopausal females with
      osteoporosis compared to postmenopausal females with preserved bone mass its low
      specificity does not warrant its utility is diagnosing osteoporosis.

PMID- 24289764
TI  - Investigation of in-vitro susceptibility of multidrug-resistant Acinetobacter
      baumannii strains isolated from clinical specimens to tigecycline.
AB  - The management of infections due to A. baumannii is difficult because of rapidly
      developing resistance, however, tigecycline, a glycylcycline antimicrobial, is in
      use for several years. In the present study, it was aimed to determine the
      susceptibility rates of A. baumannii to tigecycline. A total of 90 A. baumanni
      isolates were tested using three methods such as disk diffusion, broth
      microdilution, and E-test. The MIC50 and MIC90 values and the MIC range were
      found as 2 ug/ml, 4 ug/ml, and 0.1-8 ug/ml by microdilution; and 2 ug/ml, 6
      ug/ml, and 0.1-12 ug/ml by E-test, respectively. There were a few major errors as
      well as the minor rates were all high as between 35.7%-46.7%. The accuracy rates
      between the methods were low as 53.3% (48/90) between disk diffusion and E-test,
      51.1% (46/90) between disk diffusion and microdilution, and 60.0% (54/90) between
      E-test and microdilution. In the ROC curve analysis, an inhibition zone diameter
      of susceptibility breakpoint of 21.5 mm had sensitivity between 68.8%-88.9%;
      specificity between 81.9%-87.9%; and accuracy between 80.0%-83.33%. An analysis
      based on EUCAST's non-species breakpoints, the MIC tests showed higher accuracy
      with a rate of 96.7%, however, performance of disk diffusion got worse as lower
      than 25%. In conclusion, we showed that the reliability of the methods even did
      not remain as high as the past. Our study presented that none of three methods
      revealed reliable results in determination of susceptibility of A. baumanni to
      tigecycline, so the clinical response should be followed up carefully in such
      cases.

PMID- 24289765
TI  - BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7
      cells.
AB  - Gene expressionis controlled by epigenetic mechanisms including histone
      methylation. Osteoclasts are bone-resorptive cells that differentiate from
      hematopoietic-precursor cells by receptor activator of nuclear factor-kappaB
      ligand (RANKL) stimulation. Although BIX01294, a specific inhibitor of G9a, which
      works as a histone H3 lysine 9 (H3K9) methyltransferase, reportedly changes
      cellular differentiational stage, its effect on osteoclast differentiation is
      unclear. In this study, the effects of BIX01294 on osteoclast differentiation
      were examined. Here, we showed that BIX01294 dose-dependently reduced RANKL
      induced tartrate-resistant acid phosphatase positive multinuclear osteoclast-like
      cell differentiation from murine macrophage-like Raw264.7 cells. During
      differentiation, growth rates reduced only less than 14% of those of cells
      stimulated with RANKL alone by BIX01294 treatment. Moreover, western blot
      analysis showed that BIX01294 reduced RANKL-induced carbonic anhydrase II and
      cathepsin K production and decreased RANKL-induced nuclear factor of activated T
      cell c1, a master regulatory transcription factor, production during osteoclast
      differentiation. These results suggest that BIX01294 suppresses RANKL-induced
      osteoclast differentiation. This is the first report about the effect of BIX01294
      on osteoclast differentiation.

PMID- 24289766
TI  - Safety reporting on implantation of autologous adipose tissue-derived stem cells
      with platelet-rich plasma into human articular joints.
AB  - BACKGROUND: Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem
      cells (MSCs), have great potential as therapeutic agents in regenerative
      medicine. Numerous animal studies have documented the multipotency of ADSCs,
      showing their capabilities to differentiate into tissues such as muscle, bone,
      cartilage, and tendon. However, the safety of autologous ADSC injections into
      human joints is only beginning to be understood and the data are lacking.
      METHODS: Between 2009 and 2010, 91 patients were treated with autologous ADSCs
      with platelet-rich plasma (PRP) for various orthopedic conditions. Stem cells in
      the form of stromal vascular fraction (SVF) were injected with PRP into various
      joints (n = 100). All patients were followed for symptom improvement with visual
      analog score (VAS) at one month and three months. Approximately one third of the
      patients were followed up with third month magnetic resonance imaging (MRI) of
      the injected sites. All patients were followed up by telephone questionnaires
      every six months for up to 30 months. RESULTS: The mean follow-up time for all
      patients was 26.62 +/- 0.32 months. The follow-up time for patients who were
      treated in 2009 and early 2010 was close to three years. The relative mean VAS of
      patients at the end of one month follow-up was 6.55 +/- 0.32, and at the end of
      three months follow-up was 4.43 +/- 0.41. Post-procedure MRIs performed on one
      third of the patients at three months failed to demonstrate any tumor formation
      at the implant sites. Further, no tumor formation was reported in telephone long
      term follow-ups. However, swelling of injected joints was common and was thought
      to be associated with death of stem cells. Also, tenosinovitis and tendonitis in
      elderly patients, all of which were either self-limited or were remedied with
      simple therapeutic measures, were common as well. CONCLUSIONS: Using both MRI
      tracking and telephone follow ups in 100 joints in 91 patients treated, no
      neoplastic complications were detected at any ADSC implantation sites. Based on
      our longitudinal cohort, the autologous and uncultured ADSCs/PRP therapy in the
      form of SVF could be considered to be safe when used as percutaneous local
      injections.

PMID- 24289767
TI  - Occupational airborne contact dermatitis from benzodiazepines and other drugs.
AB  - BACKGROUND: Healthcare workers (or relatives) crushing drug tablets for patients
      with difficulties in swallowing are at risk of developing sensitization via
      airborne exposure. Tetrazepam, in particular, is increasingly being described as
      an important occupational allergen in this regard, although other drugs are also
      involved. OBJECTIVES: To identify the allergenic culprits in 4 patients, namely 2
      nurses, 1 pharmacy assistant, and 1 spouse, who all regularly crushed tablets of
      systemic drugs and presented with severe airborne dermatitis. METHODS: The
      patients were patch tested with all of the drugs that they handled, as well as
      with potential cross-sensitizing molecules. RESULTS: All 4 patients reacted to
      tetrazepam and other benzodiazepines, some of which they had not previously come
      into contact with, which favours cross-reactivity rather than concomitant
      sensitization. These patients also had positive reactions to several other non
      structurally related drugs for which, in some cases, there was no history of
      exposure. CONCLUSIONS: Subjects having to crush drugs, in either an occupational
      or a non-occupational context, and who present with dermatitis suspected of being
      airborne-induced, should be patch tested with all contacted medicaments, as well
      as with possible cross-reacting molecules. Prevention by the use of crushing
      devices and protective measures (gloves and masks) when medications are handled
      should be advised.

PMID- 24289768
TI  - Chronic rhinosinusitis: the unrecognized epidemic.

PMID- 24289769
TI  - Are the smoking-induced diseases an acquired form of cystic fibrosis?

PMID- 24289770
TI  - Studying outcomes that matter to patients and families: quality of life after
      intracerebral hemorrhage.

PMID- 24289771
TI  - Hypoxia, receptor for advanced glycation end products, and cystic fibrosis: a
      pathway to chronic inflammation?

PMID- 24289772
TI  - Human rhinovirus, wheezing illness, and the primary prevention of childhood
      asthma.

PMID- 24289773
TI  - A 14-year-old female with fixed airflow obstruction.

PMID- 24289774
TI  - Phosphodiesterase inhibitors in chronic obstructive pulmonary disease.

PMID- 24289775
TI  - GOLD Executive Summary.

PMID- 24289776
TI  - Comorbidities and chronic obstructive pulmonary disease: is there a place for
      lung fibrosis?

PMID- 24289777
TI  - Feasibility and ethics.

PMID- 24289778
TI  - Reply: Comorbidities and chronic obstructive pulmonary disease: is there a place
      for lung fibrosis?

PMID- 24289779
TI  - Reply: Feasibility and ethics.

PMID- 24289780
TI  - Vitamin C should be tested against exercise-induced bronchoconstriction.

PMID- 24289781
TI  - Surrogate consent for genetic testing, the reconsent process, and consent for
      long-term outcomes in acute respiratory distress syndrome trials.

PMID- 24289782
TI  - A familial syndrome of pulmonary nontuberculous mycobacteria infections.

PMID- 24289783
TI  - Basic research funding by philanthropic organizations: a case in point.

PMID- 24289786
TI  - Chronic expanding hematoma of the lung.

PMID- 24289787
TI  - Reversible insertion of carbenes into ruthenium-silicon bonds.
AB  - The five-coordinate carbene complexes [Ru{kappaP,P,Si-Si(Me)(C6H4-2
      PiPr2)2}Cl(?CHR)] (2, R = Ph; 3, R = SiMe3), analogues of the Grubbs catalyst,
      were prepared from the dimer [Ru(MU-Cl){kappaP,P,Si-Si(Me)(C6H4-2-PiPr2)2}]2 (1)
      and the corresponding diazoalkane N2CHR. The particular structural features that
      result from the presence of a strongly trans directing silyl group at the pincer
      ligand of these complexes are discussed on the basis of NMR information and the
      crystal structure of the vinylidene analogue [Ru{kappaP,P,Si-Si(Me)(C6H4-2
      PiPr2)2}Cl(?C?CHPh)] (4), which was also obtained from 1 and phenylacetylene. The
      reactions of 3 with reagents such as P(OMe)3, CO, NCMe, and K(acac) illustrate
      that the first response of these carbene complexes to an increase of the
      coordination number around ruthenium is the insertion of the carbene ligand into
      the Ru-Si bond. These reactions also indicate that the insertion process is
      reversible and allows typical transformations of carbene ligands such as C-H
      functionalizations via carbene insertion (in the acac ligand) or the formation of
      ketene from CO. In addition, the reactions of 3 with terminal alkynes such as
      phenylacetylene or 3,3-dimethyl-1-butyne show that the inserted carbenes can also
      undergo reactions typical of metal-bound alkyls such as alkyne insertion and C-H
      reductive elimination. 

PMID- 24289788
TI  - Angiotensin II potentiates zinc-induced cortical neuronal death by acting on
      angiotensin II type 2 receptor.
AB  - BACKGROUND: The angiotensin system has several non-vascular functions in the
      central nervous system. For instance, inhibition of the brain angiotensin system
      results in a reduction in neuronal death following acute brain injury such as
      ischemia and intracerebral hemorrhage, even under conditions of constant blood
      pressure. Since endogenous zinc has been implicated as a key mediator of ischemic
      neuronal death, we investigated the possibility that the angiotensin system
      affects the outcome of zinc-triggered neuronal death in cortical cell cultures.
      RESULTS: Exposure of cortical cultures containing neurons and astrocytes to 300
      MUM zinc for 15 min induced submaximal death in both types of cells.
      Interestingly, addition of angiotensin II significantly enhanced the zinc
      triggered neuronal death, while leaving astrocytic cell death relatively
      unchanged. Both type 1 and 2 angiotensin II receptors (AT1R and AT2R,
      respectively) were expressed in neurons as well as astrocytes. Zinc neurotoxicity
      was substantially attenuated by PD123319, a specific inhibitor of AT2R, and
      augmented by CGP42112, a selective activator of AT2R, indicating a critical role
      for this receptor subtype in the augmentation of neuronal cell death.Because zinc
      toxicity occurs largely through oxidative stress, the levels of superoxides in
      zinc-treated neurons were assessed by DCF fluorescence microscopy. Combined
      treatment with zinc and angiotensin II substantially increased the levels of
      superoxides in neurons compared to those induced by zinc alone. This increase in
      oxidative stress by angiotensin II was completely blocked by the addition of
      PD123319. Finally, since zinc-induced oxidative stress may be caused by induction
      and/or activation of NADPH oxidase, the activation status of Rac and the level of
      the NADPH oxidase subunit p67phox were measured. Angiotensin II markedly
      increased Rac activity and the levels of p67phox in zinc-treated neurons and
      astrocytes in a PD123319-dependent manner. CONCLUSION: The present study shows
      that the angiotensin system, especially that involving AT2R, may have an
      oxidative injury-potentiating effect via augmentation of the activity of NADPH
      oxidase. Hence, blockade of angiotensin signaling cascades in the brain may prove
      useful in protecting against the oxidative neuronal death that is likely to occur
      in acute brain injury.

PMID- 24289789
TI  - Characterization of pure cultures isolated from sulfamethoxazole-acclimated
      activated sludge with respect to taxonomic identification and sulfamethoxazole
      biodegradation potential.
AB  - BACKGROUND: Sulfamethoxazole (SMX, sulfonamide antibiotic) biodegradation by
      activated sludge communities (ASC) is still only partly understood. The present
      work is focusing on nine different bacteria species capable of SMX biodegradation
      that were isolated from SMX-acclimated ASC. RESULTS: Initially 110 pure cultures,
      isolated from activated sludge, were screened by UV-absorbance measurements (UV
      AM) for their SMX biodegradation potential. Identification via almost complete
      16S rRNA gene sequencing revealed five Pseudomonas spp., one Brevundimonas sp.,
      one Variovorax sp. and two Microbacterium spp.. Thus seven species belonged to
      the phylum Proteobacteria and two to Actinobacteria. These cultures were
      subsequently incubated in media containing 10 mg L(-1) SMX and different
      concentrations of carbon (sodium-acetate) and nitrogen (ammonium-nitrate).
      Different biodegradation patterns were revealed with respect to media composition
      and bacterial species. Biodegradation, validated by LC-UV measurements to verify
      UV-AM, occurred very fast with 2.5 mg L(-1) d(-1) SMX being biodegraded in all
      pure cultures in, for UV-AM modified, R2A-UV medium under aerobic conditions and
      room temperature. However, reduced and different biodegradation rates were
      observed for setups with SMX provided as co-substrate together with a
      carbon/nitrogen source at a ratio of DOC:N - 33:1 with rates ranging from 1.25 to
      2.5 mg L(-1) d(-1). CONCLUSIONS: Media containing only SMX as carbon and nitrogen
      source proved the organisms' ability to use SMX as sole nutrient source where
      biodegradation rates decreased to 1.0 - 1.7 mg L(-1) d-(1). The different
      taxonomically identified species showed specific biodegradation rates and
      behaviours at various nutrient conditions. Readily degradable energy sources seem
      to be crucial for efficient SMX biodegradation.

PMID- 24289790
TI  - Influence of FTO variants on obesity, inflammation and cardiovascular disease
      risk biomarkers in Spanish children: a case-control multicentre study.
AB  - BACKGROUND: Variants in the FTO gene have been associated with obesity in
      children, but this association has not been shown with other biomarkers. We
      assessed the association of 52 FTO polymorphisms, spanning the whole gene, with
      obesity and estimated the influence of these polymorphisms on anthropometric,
      clinical and metabolic parameters as well as inflammation and cardiovascular
      disease (CVD) risk biomarkers among Spanish children. METHODS: A multicentre case
      control study was conducted in 534 children (292 obese and 242 with normal-BMI).
      Anthropometric, clinical, metabolic, inflammation and CVD risk markers were
      compared using the Student's t-test for unpaired samples. The genotype relative
      risk was assessed by comparing the obese and normal-BMI group, calculating the
      odds ratio. The association of each SNP with phenotypic parameters was analysed
      using either logistic or linear regression analysis. RESULTS: All anthropometric,
      clinical and metabolic factors as well as inflammatory and CVD risk biomarkers
      were higher in the obese than in the normal-BMI group, except adiponectin and HDL
      c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show
      difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333)
      were positively associated with obesity and in linkage disequilibrium between
      each other; the haplotype including the risk alleles of these polymorphisms
      showed a high risk for obesity. The rs8061518 was negatively associated with
      obesity and the haplotype including this SNP and rs3826169, rs17818902 and
      rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was
      associated with weight, diastolic blood pressure, insulin, homeostatic model
      assessment of insulin resistance, leptin, and active plasminogen inhibitor
      activator-1 after sex and age adjustment; however, after an additional BMI
      adjustment, this polymorphism remained associated only with leptin. CONCLUSIONS:
      We validated the previous reported association of genetic variability in intron 1
      of the FTO gene with the risk of obesity and found no association with other
      related traits in this region of the gene. We have observed strong statistical
      evidence for an association of rs8061518 in intron 3 of the gene with decreased
      risk of obesity and low concentration of leptin.

PMID- 24289791
TI  - Porphyromonas gingivalis C-terminal signal peptidase PG0026 and HagA interact
      with outer membrane protein PG27/LptO.
AB  - Outer membrane protein PG27 is essential for secretion/maturation of conserved C
      terminal domain (CTD) proteins such as gingipains, HagA, and PG0026. To determine
      the binding partner(s) of PG27, we used a Porphyromonas gingivalis mutant strain,
      83K48, which expressed functional histidine-tagged PG27. Purification of
      histidine-tagged PG27 from 83K48 found that 136-kDa and 264-kDa proteins
      accompanied histidine-tagged PG27. Mass spectrometry revealed the 136-kDa protein
      and 264-kDa protein to be PG0026 and PG1837 (HagA), respectively. PG0026 is a C
      terminal signal peptidase which cleaves the CTDs of other CTD proteins. A cross
      linking and a native electrophoresis studies suggested the interaction between
      histidine-tagged PG27 and HagA and the interaction between histidine-tagged PG27
      and PG0026. We constructed Porphyromonas gingivalis gene disrupting mutants, and
      characterized them. PG0026 was required for the full activities of gingipains,
      whereas HagA was not. A mutation disrupting PG0026 affected localization of PG27,
      but a mutation disrupting PG1837 showed little effect on the expression and
      localizations of PG27 and PG0026. To determine the functional role of HagA, we
      used PG1837-disruptant 83K54 which expressed functional histidine-tagged PG27.
      Histidine-tagged PG27 in 83K54 was co-purified with not only PG0026 but also
      several contaminated proteins. These results suggest that PG0026 interacts with
      PG27 in the absence of HagA, and that the binding state of a PG27-PG0026 complex
      was affected and stabilized by HagA. Taken together, these data suggest that
      secreted PG0026 anchors to the cell by interacting with PG27, is stabilized by
      HagA, and functions in processing of other CTD proteins such as gingipains. 

PMID- 24289792
TI  - Impact of extracellular matrix derived from osteoarthritis subchondral bone
      osteoblasts on osteocytes: role of integrinbeta1 and focal adhesion kinase
      signaling cues.
AB  - INTRODUCTION: Our recent study indicated that subchondral bone pathogenesis in
      osteoarthritis (OA) is associated with osteocyte morphology and phenotypic
      abnormalities. However, the mechanism underlying this abnormality needs to be
      identified. In this study we investigated the effect of extracellular matrix
      (ECM) produced from normal and OA bone on osteocytic cells function. METHODS: De
      cellularized matrices, resembling the bone provisional ECM secreted from primary
      human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as
      a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4
      osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by
      confocal microscopy, scanning electron microscopy (SEM), cell attachment assays,
      zymography, apoptosis assays, qRT-PCR and western blotting. The role of
      integrinbeta1 and focal adhesion kinase (FAK) signaling pathways during these
      interactions were monitored using appropriate blocking antibodies. RESULTS: The
      ECM produced by OA SBOs contained less mineral content, showed altered
      organization of matrix proteins and matrix structure compared with the matrices
      produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM
      resulted in a decrease of integrinbeta1 expression and the de-activation of FAK
      cell signaling pathway, which subsequently affected the initial osteocytic cell's
      attachment and functions including morphological abnormalities of cytoskeletal
      structures, focal adhesions, increased apoptosis, altered osteocyte specific gene
      expression and increased Matrix metalloproteinases (MMP-2) and -9 expression.
      CONCLUSION: This study provides new insights in understanding how altered OA bone
      matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in
      OA pathogenesis.

PMID- 24289794
TI  - Participation and performance trends of East-African runners in Swiss half
      marathons and marathons held between 2000 and 2010.
AB  - BACKGROUND: This study examined the changes in participation, performance and age
      of East African runners competing in half-marathons and marathons held in
      Switzerland between 2000 and 2010. METHODS: Race times, sex, age and origin of
      East African versus Non-African finishers of half-marathon and marathon finishers
      were analyzed. RESULTS: Across time, the number of Kenyan and Ethiopian finishers
      remained stable (P > 0.05) while the number of Non-African finishers increased
      for both women and men in both half-marathons and marathons (P < 0.05). In half
      marathons, the top ten African women (71 +/- 1.4 min) and top three (62.3 +/- 0.6
      min) and top ten (62.8 +/- 0.4 min) African men were faster than their Non
      African counterparts (P < 0.05). In marathons, however, there was no difference
      in race times between the top three African men (130.0 +/- 0.0 min) and women
      (151.7 +/- 2.5 min) compared to Non-African men (129.0 +/- 1.0 min) and women
      (150.7 +/- 1.2 min) (P > 0.05). In half-marathons and marathons was no difference
      in age between the best Non-African and the best African runners (P > 0.05).
      CONCLUSIONS: During the last decade in Switzerland, the participation of Kenyan
      and Ethiopian runners in half- and full- marathons remained stable. In marathons
      there was no difference in age and performance between the top African and the
      top Non-African runners. Regarding half-marathons, the top African runners were
      faster but not younger than the top Non-African runners. Future insight should be
      gained by comparing the present results with participation, performance and age
      trends for East African runners competing in marathons held in larger countries.

PMID- 24289793
TI  - Propensity for social interaction predicts nicotine-reinforced behaviors in
      outbred rats.
AB  - Social and genetic factors can influence smoking behavior. Using olfactogustatory
      stimuli as the sensory cue for intravenous nicotine self-administration (SA), we
      previously showed that social learning of nicotine contingent odor cue prevented
      rats from developing conditioned taste aversion and allowed them to instead
      establish stable nicotine SA. We hypothesized that genetic factors influenced
      socially acquired nicotine SA. A heterogeneous stock (HS; N/NIH) of outbred rats
      was trained to self-administer nicotine using the social learning protocol. Both
      male and female HS rats acquired nicotine SA, but females self-administered more
      nicotine than males. After extinction, the context previously paired with
      nicotine SA, in conjunction with socially transmitted drug cues, was sufficient
      to cause reinstatement of drug-seeking behavior. Wide variation in both nicotine
      intake and reinstatement was observed. Using multiple regression analysis, we
      found that measures of social interaction were significant predictors of nicotine
      intake and reinstatement of drug seeking in both males and females. Furthermore,
      measures of depression were predictors of nicotine intake in both males and
      females, anxiety was a predictor only in males and response to novelty was a
      predictor only in females. In males, measures of both depression and anxiety
      predicted nicotine reinstatement. Together, these data supported the ideas that
      genetically determined propensities for emotional and social phenotypes are
      significant determinants for nicotine-reinforced behavior, and that the HS rat is
      a suitable tool for dissecting genetic mechanisms that may underlie the
      interaction between social behavior, anxiety, depression and smoking. 

PMID- 24289795
TI  - Double esophageal duplication cysts, with ectopic gastric mucosa: a case report.
AB  - Esophageal duplication cyst (EDC) is a congenital malformation of the posterior
      primitive foregut, which mainly occurs in the thoracic esophagus. Here, we
      describe a 3-year-old Han Chinese boy afflicted with intermittent fever of acute
      onset and dry cough. Thoracic computed tomography revealed an 10 cm * 5.4 cm *
      5.8 cm oval-shaped, cyst-like tumor located in the extrapleural space, extending
      along the right paravertebral gutter and compressing the trachea forward. An
      additional small-sized, oval-shaped cyst was identified in the posterior
      mediastinum, between the esophagus and the spinal column, at the T1 level. During
      open thoracotomy, under general anesthesia, an opaque, thick-walled, esophageal
      cyst was revealed not to be in communication with the esophageal lumen or the
      trachea. This cyst was subsequently resected in an en bloc manner. The small (1
      cm) esophageal cyst was left untreated based on a "wait-and-see" policy.
      Histological analysis showed that the resected cyst was walled by hyperplastic,
      fibrous tissues and locally lined with gastric mucosa inherent glands. This
      finding was consistent with a diagnosis of EDC, with ectopic gastric mucosa. The
      respiratory tract symptoms resolved immediately after the operation. Computed
      tomography obtained at the 6-month follow-up showed that no disease, residual or
      recurrence, was present after the resection of the large-sized cyst, and the
      small-sized cyst remained unchanged in size.

PMID- 24289796
TI  - Oxytocin administered during labor and breast-feeding: a retrospective cohort
      study.
AB  - OBJECTIVE: The relationship between labor physiology and the onset of lactation
      leads to assess the potential correlation between oxytocin administration during
      labor and duration of breast-feeding. METHODS: This study was designed as a
      retrospective cohort study where patients given synthetic oxytocin during labor
      induction were considered as the exposed cohort, and patients not given oxytocin
      formed the non-exposed cohort. Four hundred of the 7465 children born at our
      maternity during 2006 were randomly selected. Information about breast-feeding
      was available for 316 of these children. Eventual confounding or adjustment
      factors were analyzed using stratified and multivariate analysis. RESULTS:
      Oxytocin was used for delivery of 189 (59.8%) newborns, multiplying the risk of
      bottle-feeding by 1.451 (95% CI 1.28-1.63). The best-fit regression model of
      oxytocin use effect on bottle-feeding included sex and gestational age of the
      newborn. The use of oxytocin also multiplies the risk of breast-feeding
      withdrawal at 3 months by 2.29 (95% CI 1.41-3.74). This effect is confounded by
      maternal age, being higher for mothers under 27 years. CONCLUSION: Oxytocin
      administration during labor had some impact on both onset and duration of breast
      feeding, particularly in mothers under 27 years of age and newborns delivered at
      term. Clinical Study registered at U.S. NIH, ID: NCT01951040.

PMID- 24289797
TI  - Cannabis use and involuntary admission may mediate long-term adherence in first
      episode psychosis patients: a prospective longitudinal study.
AB  - BACKGROUND: This study aimed to examine factors associated with treatment
      adherence in first-episode psychosis (FEP) patients followed up over 8 years,
      especially involuntary first admission and stopping cannabis use. METHODS: This
      prospective, longitudinal study of FEP patients collected data on symptoms,
      adherence, functioning, and substance use. Adherence to treatment was the main
      outcome variable and was categorized as 'good' or 'bad'. Cannabis use during
      follow-up was stratified as continued use, stopped use, and never used. Bivariate
      and logistic regression models identified factors significantly associated with
      adherence and changes in adherence over the 8-year follow-up period. RESULTS: Of
      the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission,
      74.4% bad adherence, and 52% cannabis use. Good adherence at baseline was
      associated with Global Assessment of Functioning score (p = 0.019), Hamilton
      Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001).
      Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always
      good, 25% improved from bad to good. Among the improved adherence group, 95.7%
      had involuntary first admission and 38.9% stopped cannabis use. In the subgroup
      of patients with bad adherence at baseline, involuntary first admission and
      quitting cannabis use during follow up were associated with improved adherence.
      CONCLUSIONS: The long-term association between treatment adherence and type of
      first admission and cannabis use in FEP patients suggest targets for intervention
      to improve clinical outcomes.

PMID- 24289798
TI  - Real teams and their effect on the quality of care in nursing homes.
AB  - BACKGROUND: Use of teams has shown to be an important factor for organizational
      performance. However, research has shown that a team has to meet certain criteria
      and operate in a certain way to realize the potential benefits of team
      organizing. There are few studies that have examined how teams operate in the
      nursing home sector and their effect on quality of care. This study investigates
      the relationship between teams that meet an academic definition of the team
      concept and quality of care in nursing homes. METHODS: A cross-sectional survey
      of forty nursing home wards throughout Norway was used to collect the data. Five
      sources of data were utilized to test our research question: (1) self-report
      questionnaires to 444 employees, (2) interviews with 40 ward managers, (3) self
      report questionnaires to 40 ward managers, (4) telephone interviews with 378
      relatives, and (5) 900 hours of field observations. Use of teams in nursing home
      wards was assessed by field observations and by interviews with ward mangers.
      Quality of care was assessed by data from surveys and interviews with relatives
      and staff and through field observations. All data were aggregated to the ward
      level and two-level analyses were used to assess the relationships. RESULTS: The
      multi-level analyses showed that teams - as operationalized in the present study 
      were significantly positively related to two out of the three quality of care
      indices when controlled for ward size, days of sick leave and care level. One
      significant interaction effect was found between teams and days of sick leave,
      implying that the effect of teams decreased with higher numbers of days of sick
      leave. CONCLUSIONS: The results suggest that teams are related to higher levels
      of quality of care in nursing homes. However, the study shows that there is a
      substantial difference between real, functional teams that meet an academic
      definition of the concept and quasi teams, the latter having a significantly
      lower effect on quality of care. Hence, nursing home leaders, directors and ward
      leaders should be aware of the substantial differences betweens dysfunctional -
      or quasi - teams and real teams, and encourage the development of real functional
      teams to take advantage of the potential benefits of team organizing.

PMID- 24289800
TI  - Emerging antiretroviral drugs.
AB  - INTRODUCTION: The potency, tolerability and convenience of antiretroviral agents
      have all significantly improved over the past years, making lifelong HIV therapy
      easier. However, several specific needs are still unmet, including low daily pill
      burden, friendly metabolic profile, lack of (or few) drug interactions and high
      resistance barrier. AREAS COVERED: Updated summary of evidence-based information
      about the efficacy and safety of the most recently approved or forthcoming
      antiretroviral agents is provided. All data on antiretrovirals in the most
      advanced development stages available in peer-reviewed journals or presented at
      international meetings has been reviewed. EXPERT OPINION: Dolutegravir displays
      greater barrier to resistance and requires simpler administration than other
      currently existing drugs within the same class. Newer pharmacoenhancers (i.e.,
      cobicistat), CCR5 antagonists (i.e., cenicriviroc) and nucleotide prodrugs (i.e.,
      tenofovir alafenamide fumarate) show promising results and will expand the
      current HIV armamentarium. The development of newer once-daily, single-tablet
      coformulations will further improve drug adherence and maximize the success of
      antiretroviral therapy.

PMID- 24289799
TI  - Platelet-rich plasma (PRP) in chronic epicondylitis: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Tendinopathy is a difficult problem to manage and can result in
      significant patient morbidity. Currently, the clinical use of platelet-rich
      plasma (PRP) in painful tendons is widespread but its efficacy remains
      controversial. METHODS/DESIGN: This study is a single-center, randomized double
      blind controlled trial. Eighty patients will be allocated to have ultrasound (US)
      guided needling combined with a leukocyte-depleted (that is, pure) PRP or
      lidocaine each alternate week for a total of two interventions. Outcome data will
      be collected before intervention, and at 6 weeks, 3, 6, and 12 months after
      intervention. MAIN OUTCOME MEASURE: Changes in pain and activity levels, as
      assessed by Disabilities of the Arm, Shoulder and Hand (DASH-E, Spanish version)
      score, at 6 months. We will compare the percentage of patients in each group that
      achieve a successful treatment defined as a reduction of at least 25% in the DASH
      E score. Secondary outcome measures include changes in DASH-E at 3 and 12 months,
      changes in pain as assessed by the visual analogue scale (VAS) at the 6-week, 3-,
      6-, and 12-month follow-up, changes in sonographic features and neovascularity,
      and percentage of patients in each group with adverse reactions at 3, 6, and 12
      months. DISCUSSION: The results of this study will provide insights into the
      effect of pure PRP in tendon and may contribute to identifying the best protocol
      for PRP application in tendinopathies. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01945528.

PMID- 24289801
TI  - Carers' express positive views on the acceptability, efficacy and safety of
      buccal midazolam for paediatric status epilepticus.
AB  - AIM: Buccal midazolam has emerged as an effective alternative to rectal diazepam
      in the management of paediatric status epilepticus. This study aimed to identify
      carers' views on the safety, efficacy and acceptability of buccal midazolam in
      the management of this common neurological emergency. METHODS: Community-based,
      face-to-face interviews were carried out with 34 carers to evaluate the
      effectiveness, adverse effects and convenience of buccal midazolam as a rescue
      treatment for prolonged seizures. All children received 2.5 to 10 mg of
      Epistatus, a proprietary oral solution (10 mg/mL). We evaluated therapeutic
      success, time taken for seizures to cease and the need to attend the emergency
      department, together with the development of side effects, namely respiratory
      depression and sedation. RESULTS: Most of the families (91%) found that buccal
      midazolam was always, or usually, effective in stopping seizures and it prevented
      hospital admission in 65% of cases. The majority (96%) of those who had used both
      buccal midazolam and rectal diazepam preferred the former as it was easier to
      administer, more socially acceptable and did not sedate the child as much.
      CONCLUSION: Carers felt that buccal midazolam was an effective, safe and more
      acceptable alternative to rectal diazepam in the management of paediatric status
      epilepticus.

PMID- 24289802
TI  - Influence of chemical degradation on the surface properties of nano restorative
      materials.
AB  - OBJECTIVES: The aim of this in vitro study was to investigate the effect of
      chemical degradation on the surface roughness (Ra) and hardness (Knoop hardness
      number [KHN]) of nano restorative materials. METHODS: Disc-shaped specimens (5-mm
      diameter; 2-mm thick) of Filtek Z350 and TPH Spectrum composites and the Vitremer
      and Ketac Nano light-curing glass ionomer cements were prepared according to the
      manufacturers' instructions. After 24 hours, polishing procedures were performed
      and initial measurements of Ra and KHN were taken. The specimens were divided
      into 12 groups (n=10) according to material and storage media: artificial saliva,
      orange juice, and Coca-Cola. After 30 days of storage, the specimens were
      reevaluated for Ra and KHN. The pH values of the storage media were measured
      weekly. Data were tested for significant differences by repeated-measures three
      way analysis of variance and Tukey tests (p<0.05). RESULTS: Composites were found
      to present lower roughness values and higher hardness values than the ionomeric
      materials under all storage conditions. After degradation, the KHN of all
      experimental samples decreased significantly, while the Ra of the ionomeric
      materials increased, depending on the media, with a markedly negative impact of
      Coca-Cola and orange juice. There was no difference among the storage media for
      Filtek Z350 with regard to the KHN values. Nanofillers did not show any influence
      on the roughness and hardness of resin-modified glass ionomer cements and resin
      composites concerning their degradation resistance.

PMID- 24289805
TI  - rs3827440, a nonsynonymous single nucleotide polymorphism within GPR174 gene in X
      chromosome, is associated with Graves' disease in Polish Caucasian population.
AB  - Recently Chu et al. conducted a two-stage genome wide association study in
      Chinese that identified a novel X-linked Graves' disease (GD) susceptibility
      marker at rs3827440 - a nonsynonymous (P162S) nucleotide transition (519C<T)
      within G protein-coupled receptor 174 (GPR174) gene. We aimed to replicate this
      finding in Caucasians. Using the TaqMan approach we typed rs3827440 in 560 GD
      patients from Warsaw and 196 patients from Gliwice as well as ethically matched
      controls (N = 748, N = 198, respectively). We found an association of the
      rs3827440 T allele with GD using both an allelic and genotype comparison [odds
      ratio (OR) = 1.19, 95% confidence interval (CI): 1.03-1.38, P = 0.021; OR=1.32,
      95% CI: 1.03-1.69, P = 0.03, respectively]. There was no difference in
      distribution of rs3827440 alleles/genotypes vs gender, tobacco smoking,
      ophthalmopathy or age at disease onset. Also, no statistically significant
      differences were observed after stratifying patients for DRB1*03- or GD
      associated variants in CTLA4 or TSHR genes. Our study provides the first
      replication in a Caucasian population of the association between GD and rs3827440
      originally reported among Chinese. Our results also validate statistical
      methodology used by Chu et al. to detect associations with X-linked markers.

PMID- 24289806
TI  - Orthopaedic Disorders in Myotonic Dystrophy Type 1: descriptive clinical study of
      21 patients.
AB  - BACKGROUND: Myotonic Dystrophy Type 1 (DM1) is the most common form of hereditary
      myopathy presenting in adults. This autosomal-dominant systemic disorder is
      caused by a CTG repeat, demonstrating various symptoms. A mild, classic and
      congenital form can be distinguished. Often the quality of life is reduced by
      orthopaedic problems, such as muscle weakness, contractures, foot or spinal
      deformities, which limit patients' mobility.The aim of our study was to gather
      information about the orthopaedic impairments in patients with DM1 in order to
      improve the medical care of patients, affected by this rare disease. METHODS: A
      retrospective clinical study was carried out including 21 patients (11 male and
      10 female), all diagnosed with DM1 by genetic testing. All patients were seen
      during our special consultations for neuromuscular diseases, during which
      patients were interviewed and examined. We also reviewed surgery reports of our
      hospitalized patients. RESULTS: We observed several orthopaedic impairments:
      spinal deformities (scoliosis, hyperkyphosis, rigid spine), contractures (of the
      upper extremities and the lower extremities), foot deformities (equinus
      deformity, club foot, pes cavus, pes planovalgus, pes cavovarus, claw toes) and
      fractures.Five patients were affected by pulmonary diseases (obstructive airway
      diseases, restrictive lung dysfunctions). Twelve patients were affected by
      cardiac disorders (congenital heart defects, valvular heart defects, conduction
      disturbances, pulmonary hypertension, cardiomyopathy).Our patients received
      conservative therapy (physiotherapy, logopaedic therapy, ergotherapy) and we
      prescribed orthopaedic technical devices (orthopaedic custom-made shoes, insoles,
      lower and upper leg orthoses, wheelchair, Rehab Buggy). We performed surgery for
      spinal and foot deformities: the scoliosis of one patient was stabilized and
      seven patients underwent surgery for correction of foot deformities. CONCLUSIONS:
      An orthopaedic involvement in DM1 patients should not be underestimated. The most
      common orthopaedic impairments are contractures, foot deformities and spinal
      deformities. Contractures are typically located distally in the lower
      extremities, but can also occur in the hip or shoulder joints. Foot deformities
      could be treated with orthopaedic custom-made shoes, orthoses or insoles. Surgery
      is indicated for severe foot deformities or contractures.

PMID- 24289808
TI  - The effect of arginine on oral biofilm communities.
AB  - Alkali production by oral bacteria via the arginine deiminase system (ADS)
      increases the pH of oral biofilms and reduces the risk for development of carious
      lesions. This study tested the hypothesis that increased availability of arginine
      in the oral environment through an exogenous source enhances the ADS activity
      levels in saliva and dental plaque. Saliva and supra-gingival plaque samples were
      collected from 19 caries-free (CF) individuals (DMFT = 0) and 19 caries-active
      (CA) individuals (DMFT >= 2) before and after treatment, which comprised the use
      of a fluoride-free toothpaste containing 1.5% arginine, or a regular fluoride
      containing toothpaste twice daily for 4 weeks. ADS activity was measured by
      quantification of ammonia produced from arginine by oral samples at baseline,
      after washout period, 4 weeks of treatment, and 2 weeks post-treatment. Higher
      ADS activity levels were observed in plaque samples from CF compared to those of
      CA individuals (P = 0.048) at baseline. The use of the arginine toothpaste
      significantly increased ADS activity in plaque of CA individuals (P = 0.026). The
      plaque microbial profiles of CA treated with the arginine toothpaste showed a
      shift in bacterial composition to a healthier community, more similar to that of
      CF individuals. Thus, an anti-caries effect may be expected from arginine
      containing formulations due in large part to the enhancement of ADS activity
      levels and potential favorable modification to the composition of the oral
      microbiome. 

PMID- 24289807
TI  - A critical role for STIM1 in filopodial calcium entry and axon guidance.
AB  - BACKGROUND: Stromal interaction molecule 1 (STIM1), a Ca2+ sensor in the
      endoplasmic reticulum, regulates store-operated Ca2+ entry (SOCE) that is
      essential for Ca2+ homeostasis in many types of cells. However, if and how STIM1
      and SOCE function in nerve growth cones during axon guidance remains to be
      elucidated. RESULTS: We report that STIM1 and transient receptor potential
      channel 1 (TRPC1)-dependent SOCE operates in Xenopus spinal growth cones to
      regulate Ca2+ signaling and guidance responses. We found that STIM1 works
      together with TRPC1 to mediate SOCE within growth cones and filopodia. In
      particular, STIM1/TRPC1-dependent SOCE was found to mediate oscillatory
      filopodial Ca2+ transients in the growth cone. Disruption of STIM1 function
      abolished filopodial Ca2+ transients and impaired Ca2+-dependent attractive
      responses of Xenopus growth cones to netrin-1. Finally, interference with STIM1
      function was found to disrupt midline axon guidance of commissural interneurons
      in the developing Xenopus spinal cord in vivo. CONCLUSIONS: Our data demonstrate
      that STIM1/TRPC1-dependent SOCE plays an essential role in generating
      spatiotemporal Ca2+ signals that mediate guidance responses of nerve growth
      cones.

PMID- 24289809
TI  - Prevalence and correlates of medication non-adherence among kidney transplant
      recipients more than 6 months post-transplant: a cross-sectional study.
AB  - BACKGROUND: Among kidney transplant recipients, non-adherence with
      immunosuppressive medications frequently precedes allograft loss. We sought to
      determine the prevalence and correlates of medication non-adherence among kidney
      transplant recipients. METHODS: We performed a single-center, cross-sectional
      study of kidney transplant recipients who were at least 6 months post-transplant.
      We measured self-reported adherence using the Immunosuppressive Therapy Adherence
      Scale (ITAS, which is scored from 0 to 12, where higher scores indicate increased
      adherence) and barriers to adherence using the Immunosuppressive Therapy Barriers
      Scale (ITBS). We also used validated scales to measure perceived stress, health
      literacy, anxiety, depression, and interpersonal support. RESULTS: The 252
      patients included in the study were 59.9% male, 27.0% Black, and at a median of
      2.9 years post-transplant (interquartile range [IQR] 1.4-5.8). On the ITAS, 59.1%
      scored a perfect 12, 26.6% scored 10-11, and 14.3% scored 0-9. In univariate
      models, non-adherence (defined as ITAS score <=9) was significantly associated
      with increased scores on scales for perceived stress (OR 1.12, 95% CI 1.01-1.25)
      and depression (OR 1.14, 95% CI 1.02-1.28), and with more self-reported barriers
      to adherence on the ITBS (OR 1.15, 95% CI 1.08-1.22). After adjusting for
      sociodemographic factors, stress and depression were not associated with non
      adherence. Higher scores on the ITBS (corresponding to more self-described
      barriers to adherence) were associated with lower scores on the ITAS (P < 0.001).
      Several individual barriers were associated with non-adherence. CONCLUSIONS:
      Among prevalent kidney transplant recipients, a minority is non-adherent.
      Practical barriers to adherence may serve as promising targets for future
      interventions.

PMID- 24289811
TI  - The consequences of malnutrition following discharge from rehabilitation to the
      community: a systematic review of current evidence in older adults.
AB  - BACKGROUND: The prevalence of malnutrition in the rehabilitation setting is
      estimated to be 30-50%, with older adults at higher nutritional risk.
      Malnutrition also exists in the community setting, where 10-30% of adults are
      malnourished; however, the relationship between the two settings has been little
      explored. The present study aimed to determine the association between
      malnutrition in older adults admitted for rehabilitation and nutrition status,
      functional status, quality of life, institutionalisation, acute care admissions
      and mortality once discharged to the community. METHODS: Six electronic databases
      were searched for relevant publications (1990-2013) using controlled vocabulary.
      Longitudinal papers were included in which older adults (>=65 years) were
      admitted for rehabilitation if nutrition assessment was performed during
      admission with relevant outcomes measured following discharge to the community.
      RESULTS: Five observational studies were eligible for review which had similar
      populations. The five reviews comprised 1020 participants in total and, once
      discharged, follow-up ranged from immediate to 26 months. Malnutrition during
      rehabilitation was negatively associated with physical function and quality of
      life, and positively associated with risk of institutionalisation,
      hospitalisation and mortality. Although these studies were of high quality and
      strength, the overall contribution to the evidence is limited as a result of the
      small number of heterogenic studies. No intervention studies were identified.
      CONCLUSIONS: Malnutrition in older adults admitted for rehabilitation has a
      negative effect on functional recovery and quality of life following discharge to
      the community. This review highlights an evidence gap along the continuum of care
      for malnourished older adults, where further observational and intervention
      research is needed following discharge from rehabilitation to the community.

PMID- 24289812
TI  - Three-component [2+2+1] cross-cyclotrimerization of carboryne, unactivated
      alkene, and trimethylsilylalkyne co-mediated by Zr and Ni.
AB  - A three-component [2+2+1] cross-cyclotrimerization of carboryne, alkene, and
      trimethylsilylalkyne has been achieved under the cooperative action of zirconium
      and nickel, leading to the synthesis of a series of dihydrofulvenocarboranes. The
      bulkiness of the alkyne and phosphine ligand plays a key role in the selective
      formation of the products. 

PMID- 24289810
TI  - A high-throughput virus-induced gene silencing protocol identifies genes involved
      in multi-stress tolerance.
AB  - BACKGROUND: Understanding the function of a particular gene under various
      stresses is important for engineering plants for broad-spectrum stress tolerance.
      Although virus-induced gene silencing (VIGS) has been used to characterize genes
      involved in abiotic stress tolerance, currently available gene silencing and
      stress imposition methodology at the whole plant level is not suitable for high
      throughput functional analyses of genes. This demands a robust and reliable
      methodology for characterizing genes involved in abiotic and multi-stress
      tolerance. RESULTS: Our methodology employs VIGS-based gene silencing in leaf
      disks combined with simple stress imposition and effect quantification
      methodologies for easy and faster characterization of genes involved in abiotic
      and multi-stress tolerance. By subjecting leaf disks from gene-silenced plants to
      various abiotic stresses and inoculating silenced plants with various pathogens,
      we show the involvement of several genes for multi-stress tolerance. In addition,
      we demonstrate that VIGS can be used to characterize genes involved in
      thermotolerance. Our results also showed the functional relevance of NtEDS1 in
      abiotic stress, NbRBX1 and NbCTR1 in oxidative stress; NtRAR1 and NtNPR1 in
      salinity stress; NbSOS1 and NbHSP101 in biotic stress; and NtEDS1, NbETR1,
      NbWRKY2 and NbMYC2 in thermotolerance. CONCLUSIONS: In addition to widening the
      application of VIGS, we developed a robust, easy and high-throughput methodology
      for functional characterization of genes involved in multi-stress tolerance.

PMID- 24289813
TI  - Reverse halo sign on chest imaging in a renal transplant recipient.
AB  - Without proper treatment, the mortality of pulmonary mucormycosis is nearly 100%.
      Although the diagnosis is often made histologically, it can be suspected when
      patients have a reverse halo sign on computed tomography (CT) of the chest, along
      with the right clinical findings. We describe the case of a woman 7 months post
      renal transplant who presented with fevers, malaise, and chest pain. Her chest CT
      revealed a round, focal area of ground-glass attenuation surrounded by a complete
      rim of consolidation in the left upper lobe, consistent with the reverse halo
      sign. Pulmonary mucormycosis was diagnosed by transbronchial lung biopsy. She was
      successfully treated with combined medical and surgical therapies. In the context
      of this case, we provide a brief review of the diagnosis of pulmonary
      mucormycosis, with a focus on radiographic and pathologic findings.

PMID- 24289815
TI  - How health professionals conceive and construct interprofessional practice in
      rural settings: a qualitative study.
AB  - BACKGROUND: Although interprofessional practice (IPP) offers the potential to
      enhance rural health services and provide support to rural clinicians, IPP may
      itself be problematic due to workforce limitations and service fragmentation.
      Differing socioeconomic and geographic characteristics of rural communities means
      that the way that IPP occurs in rural contexts will necessarily differ from that
      occurring in metropolitan contexts. The aim of this study was to investigate the
      factors contributing to effective IPP in rural contexts, to examine how IPP
      happens and to identify barriers and enablers. METHODS: Using Realistic
      Evaluation as a framework, semi-structured interviews were conducted with health
      professionals in a range of rural healthcare contexts in NSW, Australia.
      Independent thematic analysis was undertaken by individual research team members,
      which was then integrated through consensus to achieve a qualitative description
      of rural IPP practice. RESULTS: There was clear evidence of diversity and
      complexity associated with IPP in the rural settings that was supported by
      descriptions of collaborative integrated practice. There were instances where IPP
      doesn't and could happen. There were a number of characteristics identified that
      significantly impacted on IPP including the presence of a shared philosophical
      position and valuing of IPP and recognition of the benefits, funding to support
      IPP, pivotal roles, proximity and workforce resources. CONCLUSIONS: The nature of
      IPP in rural contexts is diverse and determined by a number of critical factors.
      This study goes some of the way towards unravelling the complexity of IPP in
      rural contexts, highlighting the strong motivating factors that drive IPP.
      However, it has also identified significant structural and relational barriers
      related to workload, workforce, entrenched hierarchies and ways of working and
      service fragmentation. Further research is required to explicate the mechanisms
      that drive successful IPP across a range of diverse rural contexts in order to
      inform the implementation of robust flexible strategies that will support
      sustainable models of rural IPP.

PMID- 24289814
TI  - Genetic variation within the Chrna7 gene modulates nicotine reward-like
      phenotypes in mice.
AB  - Mortality from tobacco smoking remains the leading cause of preventable death in
      the world, yet current cessation therapies are only modestly successful,
      suggesting new molecular targets are needed. Genetic analysis of gene expression
      and behavior identified Chrna7 as potentially modulating nicotine place
      conditioning in the BXD panel of inbred mice. We used gene targeting and
      pharmacological tools to confirm the role of Chrna7 in nicotine conditioned place
      preference (CPP). To identify molecular events downstream of Chrna7 that may
      modulate nicotine preference, we performed microarray analysis of alpha7 knock
      out (KO) and wild-type (WT) nucleus accumbens (NAc) tissue, followed by
      confirmation with quantitative polymerase chain reaction (PCR) and
      immunoblotting. In the BXD panel, we found a putative cis expression quantitative
      trait loci (eQTL) for Chrna7 in NAc that correlated inversely to nicotine CPP. We
      observed that gain-of-function alpha7 mice did not display nicotine preference at
      any dose tested, whereas conversely, alpha7 KO mice demonstrated nicotine place
      preference at a dose below that routinely required to produce preference. In B6
      mice, the alpha7 nicotinic acetylcholine receptor (nAChR)-selective agonist, PHA
      543613, dose-dependently blocked nicotine CPP, which was restored using the
      alpha7 nAChR-selective antagonist, methyllycaconitine citrate (MLA). Our genomic
      studies implicated a messenger RNA (mRNA) co-expression network regulated by
      Chrna7 in NAc. Mice lacking Chrna7 demonstrate increased insulin signaling in the
      NAc, which may modulate nicotine place preference. Our studies provide novel
      targets for future work on development of more effective therapeutic approaches
      to counteract the rewarding properties of nicotine for smoking cessation. 

PMID- 24289816
TI  - The dynamic pipeline: hydraulic capacitance and xylem hydraulic safety in four
      tall conifer species.
AB  - Recent work has suggested that plants differ in their relative reliance on
      structural avoidance of embolism versus maintenance of the xylem water column
      through dynamic traits such as capacitance, but we still know little about how
      and why species differ along this continuum. It is even less clear how or if
      different parts of a plant vary along this spectrum. Here we examined how traits
      such as hydraulic conductivity or conductance, xylem vulnerability curves, and
      capacitance differ in trunks, large- and small-diameter branches, and foliated
      shoots of four species of co-occurring conifers. We found striking similarities
      among species in most traits, but large differences among plant parts.
      Vulnerability to embolism was high in shoots, low in small- and large-diameter
      branches, and high again in the trunks. Safety margins, defined as the pressure
      causing 50% loss of hydraulic conductivity or conductance minus the midday water
      potential, were large in small-diameter branches, small in trunks and negative in
      shoots. Sapwood capacitance increased with stem diameter, and was correlated with
      stem vulnerability, wood density and latewood proportion. Capacitive release of
      water is a dynamic aspect of plant hydraulics that is integral to maintenance of
      long-distance water transport. 

PMID- 24289817
TI  - Voluntary contraction of the tensor tympani muscle and its audiometric effects.
AB  - BACKGROUND: The tensor tympani muscle is the largest muscle within the middle
      ear. Its voluntary contraction is a very unusual event. Only a few papers have
      documented its audiometric effects. OBJECTIVE: To report an unusual case of
      voluntary tensor tympani muscle contraction and describe its audiometric effects.
      CASE REPORT: A 27-year-old man, who presented complaining of voluntarily evoked
      bilateral tinnitus, was found to be able to voluntarily contract the tensor
      tympani muscle in both ears simultaneously. Audiograms were performed under
      conditions of rest and maximal contraction of the tensor tympani muscle. The most
      remarkable effects were conductive hearing loss at lower frequencies and an
      increase in middle-ear impedance. CONCLUSION: The importance of the tensor
      tympani muscle in middle-ear physiology remains unclear. It has been related to
      the attenuation of sounds produced during the mastication process. Voluntary
      control over the tensor tympani muscle is an extremely rare event. However, an
      understanding of the potential audiometric effects of its contraction could aid
      the diagnosis of hearing disorders.

PMID- 24289818
TI  - Antipsychotic agents screened as human carbonic anhydrase I and II inhibitors.
AB  - The antipsychotic drugs currently used to treat schizophrenia can be divided into
      two distinct classes, typical and atypical antipsychotics. Many drug molecules
      are enzyme inhibitors that bind reversibly or irreversibly to their target
      through intermolecular interactions. That's why enzyme inhibition studies are an
      important issue for drug design and biochemical applications. In this study, in
      vitro inhibition effect of some antipsychotic drugs on the purified carbonic
      anhydrase (CA) I and II isoenzymes were investigated by using CO2 as a substrate.
      CA I and II were purified from human erythrocytes by a simple one step procedure
      using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The results showed
      that all the drugs inhibited the cytosolic carbonic anhydrases enzyme activity in
      a concentration-dependent fashion. Among the studied drugs, aripiprazole and
      pramipexole were found to be the most active one for hCA I (IC50: 3.64 and 5.37
      MUM) and hCA II (IC50: 4.16 and 4.81 MUM) activity, respectively.

PMID- 24289819
TI  - Growth cone-specific functions of XMAP215 in restricting microtubule dynamics and
      promoting axonal outgrowth.
AB  - BACKGROUND: Microtubule (MT) regulators play essential roles in multiple aspects
      of neural development. In vitro reconstitution assays have established that the
      XMAP215/Dis1/TOG family of MT regulators function as MT 'plus-end-tracking
      proteins' (+TIPs) that act as processive polymerases to drive MT growth in all
      eukaryotes, but few studies have examined their functions in vivo. In this study,
      we use quantitative analysis of high-resolution live imaging to examine the
      function of XMAP215 in embryonic Xenopus laevis neurons. RESULTS: Here, we show
      that XMAP215 is required for persistent axon outgrowth in vivo and ex vivo by
      preventing actomyosin-mediated axon retraction. Moreover, we discover that the
      effect of XMAP215 function on MT behavior depends on cell type and context. While
      partial knockdown leads to slower MT plus-end velocities in most cell types, it
      results in a surprising increase in MT plus-end velocities selective to growth
      cones. We investigate this further by using MT speckle microscopy to determine
      that differences in overall MT translocation are a major contributor of the
      velocity change within the growth cone. We also find that growth cone MT
      trajectories in the XMAP215 knockdown (KD) lack the constrained co-linearity that
      normally results from MT-F-actin interactions. CONCLUSIONS: Collectively, our
      findings reveal unexpected functions for XMAP215 in axon outgrowth and growth
      cone MT dynamics. Not only does XMAP215 balance actomyosin-mediated axon
      retraction, but it also affects growth cone MT translocation rates and MT
      trajectory colinearity, all of which depend on regulated linkages to F-actin.
      Thus, our analysis suggests that XMAP215 functions as more than a simple MT
      polymerase, and that in both axon and growth cone, XMAP215 contributes to the
      coupling between MTs and F-actin. This indicates that the function and regulation
      of XMAP215 may be significantly more complicated than previously appreciated, and
      points to the importance of future investigations of XMAP215 function during MT
      and F-actin interactions.

PMID- 24289821
TI  - Clinical and regulatory implications of active run-in phases in long-term studies
      for bipolar disorder.
AB  - OBJECTIVE: The integration of new treatments into the market and routine clinical
      practice should be dependent on robustness of evidence from randomised controlled
      trials (RCTs). We assessed study designs of long-term studies for bipolar
      disorder of all second-generation antipsychotics (SGAs) submitted to the Food and
      Drug Administration (FDA) and the completeness of evidence submitted to the
      regulatory agency. METHOD: Systematic review of double-blind RCTs comparing SGAs
      with placebo or active drugs in adults. FDA website and electronic databases were
      searched until July 2013. RESULTS: Six placebo-controlled trials comparing
      aripiprazole, olanzapine, quetiapine and ziprasidone were found in the FDA
      website. Electronic searches found four additional RCTs about aripiprazole,
      olanzapine or quetiapine. All RCTs (either submitted to FDA or not) selected
      patients who responded to acute treatment to increase the treatment effect
      observed in the long-term phase (enrichment design). By contrast, in the
      prescribing information sheets for all SGAs, the reported indication was
      'maintenance treatment of bipolar disorder'. CONCLUSION: Extrapolation of results
      from enrichment studies to the more general population of patients should be
      carried out cautiously because average treatment benefits are likely to be less
      in unselected patients. Clear guidance for regulatory submission of RCTs is
      needed.

PMID- 24289822
TI  - The latest pharmacotherapy options for type 1 diabetes.
AB  - INTRODUCTION: Pharmacotherapy of type 1 diabetes (T1D) is mainly restricted to
      insulin treatment. Insulin analogues have replaced human insulin sometimes
      without reason. A broader approach is needed. AREAS COVERED: Insulin and insulin
      analogues, but also other available hormone therapies and drugs, based on
      literature in PubMed are included in this study. EXPERT OPINION: At diagnosis,
      T1D patients should, when resources allow, participate in clinical trials aiming
      at preservation of beta cell function, for example, with combination therapies
      involving auto-antigen/s. In very young children insulin pump is recommended,
      when enough resources for ALL patients; in older patients pump or multiple
      insulin therapy is recommended. Human insulin still has a place, with insulin
      analogues on special indications. Patients with pronounced insulin resistance
      might need Metformin, and Glitazones need more studies. Incretins, for example,
      GLP-1 may be of interest in patients with residual C-peptide. Amylin will
      probably be restricted to highly motivated patients. IGF-1 also requires more
      studies. C-peptide may be a hormone, probably part of future treatment.
      Glucosoxidase inhibitors might be considered in obese patients. Whether drugs
      increasing glucosuria will be of clinical value in T1D remains to be shown. In
      summary, insulin replacement is not enough for several patients. A broader
      pharmacotherapy is needed, at onset, and later when metabolic control needs
      improvement.

PMID- 24289820
TI  - Amyloid beta-protein oligomers and Alzheimer's disease.
AB  - The oligomer cascade hypothesis, which states that oligomers are the initiating
      pathologic agents in Alzheimer's disease, has all but supplanted the amyloid
      cascade hypothesis, which suggested that fibers were the key etiologic agents in
      Alzheimer's disease. We review here the results of in vivo, in vitro and in
      silico studies of amyloid beta-protein oligomers, and discuss important caveats
      that should be considered in the evaluation of these results. This article is
      divided into four sections that mirror the main approaches used in the field to
      better understand oligomers: (1) attempts to locate and examine oligomers in vivo
      in situ; that is, without removing these species from their environment; (2)
      studies involving oligomers extracted from human or animal tissues and the
      subsequent characterization of their properties ex vivo; (3) studies of oligomers
      that have been produced synthetically and studied using a reductionist approach
      in relatively simple in vitro biophysical systems; and (4) computational studies
      of oligomers in silico. These multiple orthogonal approaches have revealed much
      about the molecular and cell biology of amyloid beta-protein. However, as
      informative as these approaches have been, the amyloid beta-protein oligomer
      system remains enigmatic. 

PMID- 24289823
TI  - The impact of real-time 3d imaging by ultra-high speed optical coherence
      tomography in urothelial carcinoma.
AB  - BACKGROUND: Optical coherence tomography (OCT) has become a promising diagnostic
      tool in many medical fields. In particular, noninvasive real-time optical biopsy
      of internal organs is one of the most attractive applications of OCT, enabling in
      situ diagnosis of carcinoma at an early stage. We used an ultra-high speed OCT
      system for real-time three-dimensional (3D) imaging of three excised specimens of
      advanced urothelial carcinoma (UC) and investigated the association of the images
      with results from histopathological examination. CASE PRESENTATIONS: Case 1 was a
      69-year-old man underwent radical cystectomy for muscle-invasive UC (pT2). Case 2
      was a 53-year-old man underwent laparoscopic nephroureterectomy and partial
      cystectomy for left ureter carcinoma (pT2) and case 3 was a 77-year-old woman
      underwent radical cystectomy for advanced bladder carcinoma (pT3b). Real-time 3D
      OCT images of normal bladder wall and ureter showed three layers, including the
      urothelium, lamina propria, and muscularis layer. In contrast, normal structure
      was not seen in the muscle-invasive UC area or the scar tissue area. CONCLUSIONS:
      This study highlighted a new diagnostic method with potential application for UC
      diagnosis. We will investigate more cases in the future and expect improvement in
      the diagnosing efficiency of carcinoma in situ or organ-confined muscle-invasive
      cancer by cystoscopy or ureteroscopy with ultra-high speed OCT.

PMID- 24289824
TI  - Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis,
      experimental validation and clinical significance.
AB  - BACKGROUND: The diagnostic and prognostic value of microRNA (miRNA) expression
      aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied
      extensively in recent years. However, differences in measurement platforms and
      lab protocols as well as small sample sizes can render gene expression levels
      incomparable. METHODS: A comprehensive meta-review of published studies in PDAC
      that compared the miRNA expression profiles of PDAC tissues and paired
      neighbouring noncancerous pancreatic tissues was performed to determine candidate
      miRNA biomarkers for PDAC. Both a miRNA vote-counting strategy and a recently
      published Robust Rank Aggregation method were employed. In this review, a total
      of 538 tumour and 206 noncancerous control samples were included. RESULTS: We
      identified a statistically significant miRNA meta-signature of seven up- and
      three down-regulated miRNAs. The experimental validation results showed that the
      miRNA expression levels were in accordance with the meta-signature. The results
      from the vote-counting strategy were consistent with those from the Robust Rank
      Aggregation method. The experimental validation confirmed that the statistically
      unique profiles identified by the meta-review approach could discriminate PDAC
      tissues from paired nonmalignant pancreatic tissues. In a cohort of 70 patients,
      the high expression of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-31
      (p=0.039, HR=2.735; 95% CI=1.317-6.426), the low expression of miR-375 (p=0.022,
      HR=2.337; 95% CI=1.431-5.066) were associated with poor overall survival
      following resection, independent of clinical covariates. CONCLUSIONS: The
      identified miRNAs may be used to develop a panel of diagnostic and prognostic
      biomarkers for PDAC with sufficient sensitivity and specificity for use in a
      clinical setting.

PMID- 24289825
TI  - Safety and patients' satisfaction of transcutaneous supraorbital neurostimulation
      (tSNS) with the Cefaly(r) device in headache treatment: a survey of 2,313
      headache sufferers in the general population.
AB  - BACKGROUND: Transcutaneous supraorbital nerve stimulation (tSNS) with the
      Cefaly(r) device was recently found superior to sham stimulation for episodic
      migraine prevention in a randomized trial. Its safety and efficiency in larger
      cohorts of headache sufferers in the general population remain to be
      determined.The objective of this study was to assess the satisfaction with the
      Cefaly(r) device in 2,313 headache sufferers who rented the device for a 40-day
      trial period via Internet. METHODS: Only subjects using specific anti-migraine
      drugs, and thus most likely suffering from migraine, were included in the survey.
      Adverse events (AEs) and willingness to continue tSNS were monitored via phone
      interviews after the trial period. A built-in software allowed monitoring the
      total duration of use and hence compliance in subjects who returned the device to
      the manufacturer after the trial period. RESULTS: After a testing period of 58.2
      days on average, 46.6% of the 2,313 renters were not satisfied and returned the
      device, but the compliance check showed that they used it only for 48.6% of the
      recommended time. The remaining 54.4% of subjects were satisfied with the tSNS
      treatment and willing to purchase the device. Ninety-nine subjects out of the
      2,313 (4.3%) reported one or more AEs, but none of them was serious. The most
      frequent AEs were local pain/intolerance to paresthesia (47 subjects, i.e.
      2.03%), arousal changes (mostly sleepiness/fatigue, sometimes insomnia, 19
      subjects, i.e. 0.82%), headache after the stimulation (12 subjects, i.e. 0.52%).
      A transient local skin allergy was seen in 2 subjects, i.e. 0.09%. CONCLUSIONS:
      This survey of 2,313 headache sufferers in the general population confirms that
      tSNS with is a safe and well-tolerated treatment for migraine headaches that
      provides satisfaction to a majority of patients who tested it for 40 days. Only
      4.3% of subjects reported AEs, all of them were minor and fully reversible.

PMID- 24289826
TI  - Cutting through the complexity: the role of brain-derived neurotrophic factor in
      post-traumatic epilepsy (Commentary on Gill et al.).

PMID- 24289827
TI  - Central nesfatin-1 influences the excitability of ghrelin-responsive gastric
      distension neurons in the arcuate nucleus and reduces gastric motility in rats.
AB  - Although the novel satiety peptide nesfatin-1 has been shown to regulate gastric
      motility, the underlying mechanisms have yet to be elucidated. The study aimed to
      explore the effects of nesfatin-1 on ghrelin-responsive gastric distension (GD)
      neurons in the arcuate nucleus (Arc), and potential regulation mechanisms of
      gastric motility by the paraventricular nucleus (PVN). Single-unit discharges in
      the Arc were recorded extracellularly, and gastric motility in conscious rats was
      monitored during the administration of nesfatin-1 to the Arc or electrical
      stimulation of the PVN. Retrograde tracing and fluo-immunohistochemistry staining
      were used to determine NUCB2/nesfatin-1 neuronal projections. Nesfatin-1
      inhibited most of the ghrelin-responsive GD-excitatory neurons, but excited
      ghrelin-responsive GD-inhibitory neurons in the Arc. Gastric motility was
      significantly reduced by nesfatin-1 administration to the Arc in a dose-dependent
      manner. The firing activity in the Arc and changes to gastric motility were
      partly reduced by SHU9119, an antagonist of melanocortin 3/4 receptors.
      Electrical stimulation of PVN excited most of the ghrelin-responsive GD neurons
      in the Arc and promoted gastric motility. Nonetheless, pretreatment with an anti
      NUCB2/nesfatin-1 antibody in the Arc further increased the firing rate of most of
      the ghrelin-responsive GD-excitatory neurons and decreased the ghrelin-responsive
      GD-inhibitory neurons following electrical stimulation of the PVN. Gastric
      motility was enhanced by pretreatment with an anti-NUCB2/nesfatin-1 antibody in
      the Arc following PVN stimulation. Furthermore, NUCB2/nesfatin-1/fluorogold
      double-labeled neurons were detected in the PVN. These results suggest that
      nesfatin-1 could serve as an inhibitory factor in the Arc to regulate gastric
      motility via the melanocortin pathway. The PVN could be involved in the
      regulation of the Arc in gastric activity. 

PMID- 24289828
TI  - Infusion of autologous bone marrow mononuclear cells leads to transient reduction
      in proteinuria in treatment refractory patients with Idiopathic membranous
      nephropathy.
AB  - BACKGROUND: The current treatment options for idiopathic membranous nephropathy
      (IMN) carry significant toxicity. In this prospective, observational pilot study,
      we used single time infusion of bone marrow derived autologous mononuclear cells
      (MNCs) in adult patients with treatment refractory IMN. METHODS: Twelve patients
      of biopsy proven IMN who had failed a cyclical 6-month regimen of steroid and
      cyclophosphamide were enrolled in the study. Bone-marrow was harvested from the
      iliac crest and underwent processing to isolate MNCs. Cells were counted and
      subjected to viability testing before being infused through a peripheral vein on
      the same day. After the infusion, subjects were followed up monthly for the next
      six months. Supportive treatment including angiotensin antagonists and statins
      was continued throughout the study period. RESULT: The proteinuria, serum albumin
      and creatinine values at entry were 2.97 +/- 0.6 gm/1.73 m2/d, 2.27 +/- 1.1 gm/l
      and 0.9 +/- 0.8 mg/dl respectively. There was a reduction in proteinuria (p <
      0.0001), and increase in serum albumin (p = 0.001) at 1 month, with 64% of the
      subjects showing >50% reduction in proteinuria. However, the response was ill
      sustained. At 6 months, only 2 patients had >50% reduction. Serum creatinine
      remained stable throughout the study period. No infusion related side effects
      were noted. CONCLUSION: Autologous mononuclear cell infusion leads to transitory
      reduction in proteinuria and improvement in serum albumin in treatment refractory
      IMN. This effect, however, is transient. Whether this can be overcome by repeated
      infusion of cultured mesenchymal cells needs to be investigated.

PMID- 24289829
TI  - Prolonged respiratory viral shedding in transplant patients.
AB  - Respiratory viral infections are frequent causes of morbidity in transplant
      patients. We screened symptomatic adult transplant recipients for respiratory
      viruses in a cohort of patients attending a referral medical center in Brazil.
      The duration of viral shedding and the prevalence of viral codetections were also
      determined. During a 1-year period (2011-2012), swabs were obtained from 50
      patients. An in-house polymerase chain reaction panel designed to detect 10
      viruses was used. Viruses were identified in 19 (38%) patients, particularly
      parainfluenza III (32%) and the respiratory syncytial virus (20%); multiple
      viruses were identified in 26% of patients. Prolonged viral shedding was observed
      with 60% of individuals excreting viruses for >10 days. The clinical and
      epidemiologic relevance of prolonged viral shedding remains to be determined.

PMID- 24289830
TI  - The rice OsV4 encoding a novel pentatricopeptide repeat protein is required for
      chloroplast development during the early leaf stage under cold stress.
AB  - Pentatricopeptide repeat (PPR) proteins, characterized by tandem arrays of a 35
      amino acid motif, have been suggested to play central and broad roles in
      modulating the expression of organelle genes in plants. However, the molecular
      mechanisms of most rice PPR genes remains unclear. In this paper, we isolated and
      characterized a temperature-conditional virescent mutant, OsV4, in rice (Oryza
      sativa cultivar Jiahua1 (WT, japonica rice variety)). The mutant displays albino
      phenotype and abnormal chloroplasts at the three leaf stage, which gradually
      turns green after the four leaf stage at a low temperature (20  degrees C). But
      the mutant always develops green leaves and well-developed chloroplasts at a high
      temperature (32  degrees C). Genetic and molecular analyses uncovered that OsV4
      encodes a novel chloroplast-targeted PPR protein including four PPR motifs.
      Further investigations show that the mutant phenotype is associated with changes
      in chlorophyll content and chloroplast development. The OsV4 transcripts only
      accumulate to high levels in young leaves, indicating that its expression is
      tissue-specific. In addition, transcript levels of some ribosomal components and
      plastid-encoded polymerase-dependent genes are dramatically reduced in the albino
      mutants grown at 20  degrees C. These findings suggest that OsV4 plays an
      important role during early chloroplast development under cold stress in rice.

PMID- 24289831
TI  - Type 2 diabetes patients' preferences and willingness to pay for lifestyle
      programs: a discrete choice experiment.
AB  - BACKGROUND: Participation rates of lifestyle programs among type 2 diabetes
      mellitus (T2DM) patients are less than optimal around the globe. Whereas research
      shows notable delays in the development of the disease among lifestyle program
      participants. Very little is known about the relative importance of barriers for
      participation as well as the willingness of T2DM patients to pay for
      participation in such programs. The aim of this study was to identify the
      preferences of T2DM patients with regard to lifestyle programs and to calculate
      participants' willingness to pay (WTP) as well as to estimate the potential
      participation rates of lifestyle programs. METHODS: A Discrete Choice Experiment
      (DCE) questionnaire assessing five different lifestyle program attributes was
      distributed among 1250 Dutch adults aged 35-65 years with T2DM, 391
      questionnaires (31%) were returned and included in the analysis. The relative
      importance of the program attributes (i.e., meal plan, physical activity (PA)
      schedule, consultation structure, expected program outcome and out-of-pocket
      costs) was determined using panel-mixed logit models. Based on the retrieved
      attribute estimates, patients' WTP and potential participation rates were
      determined. RESULTS: The out-of-pocket costs (beta = -0.75, P < .001),
      consultation structure (beta = -0.46, P < .001) and expected outcome (beta =0.72,
      P < .001) were the most important factors for respondents when deciding whether
      to participate in a lifestyle program. Respondents were willing to pay ?128 per
      year for individual instead of group consultation and ?97 per year for 10
      kilograms anticipated weight loss. Potential participation rates for different
      lifestyle-program scenarios ranged between 48.5% and 62.4%. CONCLUSIONS: When
      deciding whether to participate in a lifestyle program, T2DM patients are mostly
      driven by low levels of out-of-pocket costs. Thereafter, they prefer individual
      consultation and high levels of anticipated outcomes with respect to weight loss.

PMID- 24289832
TI  - Patient initiated clinics for patients with chronic or recurrent conditions
      managed in secondary care: a systematic review of patient reported outcomes and
      patient and clinician satisfaction.
AB  - BACKGROUND: The cost to the NHS of missed or inappropriate hospital appointments
      is considerable. Alternative methods of appointment scheduling might be more
      flexible to patients' needs without jeopardising health and service quality. The
      objective was to systematically review evidence of patient initiated clinics in
      secondary care on patient reported outcomes among patients with chronic/recurrent
      conditions. METHODS: Seven databases were searched from inception to June 2013.
      Hand searching of included studies references was also conducted. Studies
      comparing the effects of patient initiated clinics with traditional consultant
      led clinics in secondary care for patients with long term chronic or recurrent
      diseases on health related quality of life and/or patient satisfaction were
      included. Data was extracted by one reviewer and checked by a second. Results
      were synthesised narratively. RESULTS: Seven studies were included in the review,
      these covered a total of 1,655 participants across three conditions: breast
      cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting
      was variable. Results showed no significant differences between the intervention
      and control groups for psychological and health related quality of life outcomes
      indicating no evidence of harm. Some patients reported significantly more
      satisfaction using patient-initiated clinics than usual care (p < 0.001).
      CONCLUSIONS: The results show potential for patient initiated clinics to result
      in greater patient and clinician satisfaction. The patient-consultant
      relationship appeared to play an important part in patient satisfaction and
      should be considered an important area of future research as should the presence
      or absence of a guidebook to aid self-management. Patient initiated clinics fit
      the models of care suggested by policy makers and so further research into long
      term outcomes for patients and service use in this area of practice is both
      relevant and timely.

PMID- 24289835
TI  - New insights into multiple sclerosis and advances in multiple sclerosis
      spasticity management.

PMID- 24289833
TI  - Predicting risk of mortality in dialysis patients: a retrospective cohort study
      evaluating the prognostic value of a simple chest X-ray.
AB  - BACKGROUND: Clinical outcomes of dialysis patients are variable, and improved
      knowledge of prognosis would inform decisions regarding patient management. We
      assessed the value of simple, chest X-ray derived measures of cardiac size
      (cardiothoracic ratio (CTR)) and vascular calcification (Aortic Arch
      Calcification (AAC)), in predicting death and improving multivariable prognostic
      models in a prevalent cohort of hemodialysis patients. METHODS: Eight hundred and
      twenty-four dialysis patients with one or more postero-anterior (PA) chest X-ray
      were included in the study. Using a validated calcification score, the AAC was
      graded from 0 to 3. Cox proportional hazards models were used to assess the
      association between AAC score, CTR, and mortality. AAC was treated as a
      categorical variable with 4 levels (0,1,2, or 3). Age, race, diabetes, and heart
      failure were adjusted for in the multivariable analysis. The criterion for
      statistical significance was p<0.05. RESULTS: The median CTR of the sample was
      0.53 [IQR=0.48,0.58] with calcification scores as follows: 0 (54%), 1 (24%), 2
      (17%), and 3 (5%). Of 824 patients, 152 (18%) died during follow-up. Age, sex,
      race, duration of dialysis, diabetes, heart failure, ischemic heart disease and
      baseline serum creatinine and phosphate were included in a base Cox model. Both
      CTR (HR 1.78[1.40,2.27] per 0.1 unit change), area under the curve
      (AUC)=0.60[0.55,0.65], and AAC (AAC 3 vs 0 HR 4.35[2.38,7.66], AAC 2 vs 0 HR
      2.22[1.41,3.49], AAC 1 vs 0 HR 2.43[1.64,3.61]), AUC=0.63[0.58,0.68]) were
      associated with death in univariate Cox analysis. CTR remained significant after
      adjustment for base model variables (adjusted HR 1.46[1.11,1.92]), but did not
      increase the AUC of the base model (0.71[0.66,0.76] vs. 0.71[0.66,0.76]) and did
      not improve net reclassification performance (NRI=0). AAC also remained
      significant on multivariable analysis, but did not improve net reclassification
      (NRI=0). All ranges were based on 95% confidence intervals. CONCLUSIONS: Neither
      CTR nor AAC assessed on chest x-ray improved prediction of mortality in this
      prevalent cohort of dialysis patients. Our data do not support the clinical
      utility of X-ray measures of cardiac size and vascular calcification for the
      purpose of mortality prediction in prevalent hemodialysis patients. More advanced
      imaging techniques may be needed to improve prognostication in this population.

PMID- 24289834
TI  - Characteristics and management of congenital esophageal stenosis: findings from a
      multicenter study.
AB  - BACKGROUND: Congenital esophageal stenosis (CES) is a rare condition frequently
      associated with esophageal atresia (EA). There are limited data from small series
      about the presentation, treatment, and outcomes of CES. METHODS: Medical records
      of all patients with CES included in the French Network on Esophageal
      Malformations and Congenital Diseases were reviewed retrospectively with regard
      to diagnosis, treatment, and outcome. RESULTS: Over 18 years, 61 patients (30
      boys) had CES, and 29 (47%) of these patients also had EA. The mean age at
      diagnosis was 24 months (1 day to 14 years) and was younger in patients with CES
      and EA than in those with isolated CES (7 vs. 126 months, p < 0.05). Twenty-one
      of the 61 patients with CES had no clinical symptoms: in three patients, the
      findings were incidental, and in 18 of the 29 patients with associated EA, CES
      was diagnosed at the time of surgical repair of EA or during a postoperative
      systematic esophageal barium study. In the 40 other patients, at diagnosis, 50%
      presented with dysphasia, 40% with vomiting, 50% with food impaction, and 42%
      with respiratory symptoms. Diagnosis of CES was confirmed by esophageal barium
      study (56/61) and/or esophageal endoscopy (50/61). Sixteen patients had
      tracheobronchial remnants (TBR), 40 had fibromuscular stenosis (FMS), and five
      had membrane stenosis (MS). Thirty-four patients (56%) were treated by dilation
      only (13/34 remained asymptomatic at follow-up); 15 patients were treated by
      dilation but required later surgery because of failure (4/15 remained
      asymptomatic at follow-up); and nine patients had a primary surgical intervention
      (4/9 were asymptomatic at follow-up). Dilation was complicated by esophageal
      perforation in two patients (3.4%). At follow-up, dysphagia remained in 36%
      (21/58) of patients, but the incidence did not differ between the EA and the
      isolated CS groups (10/29 vs. 7/32, p = 0.27). CONCLUSIONS: CS diagnosis can be
      delayed when associated with EA. Dilation may be effective for treating patients
      with FMS and MS, but surgical repair is often required for those with TBR. Our
      results show clearly that, regardless of the therapeutic option, dysphagia occurs
      frequently, and patients with CES should be followed over the long term.

PMID- 24289836
TI  - Environmental factors in multiple sclerosis.
AB  - Although genetic susceptibility explains the clustering of multiple sclerosis
      (MS) cases within families, the changes in MS risk that occur with migration can
      be explained only by changes in the environment. The strongest known risk factor
      for MS is infection with Epstein-Barr virus (EBV). Compared with uninfected
      individuals, the hazard of developing MS is approximately 15-fold higher among
      individuals infected with EBV in childhood and about 30-fold higher among those
      infected with EBV in adolescence or later in life. Although the mechanisms
      underlying this association remain unclear, the data provide strong evidence of a
      causal relation between EBV infection and MS risk. Relevant aspects of MS
      epidemiology beyond genetics are not explained by EBV involvement, however,
      implying the involvement of other factors. Modifiable factors for MS risk include
      smoking and childhood obesity. Increased risk of MS in individuals with vitamin D
      insufficiency has been proposed to explain the strong latitude gradient in MS
      prevalence. Results of case-control studies that relied on prevalent MS cases
      have been mixed, however, and potentially influenced by selection and recall
      biases. In a recent case-control study of individuals presenting with a first
      demyelinating episode, higher levels of vitamin D, sun exposure or actinic damage
      were found to be associated with reduced MS risk. Two longitudinal studies have
      thus far been completed. In the first, based on assessment of vitamin D intake
      from diet and supplements, the risk of MS was found to be 30% lower among women
      in the highest quintile compared with those in the lowest quintile. In the second
      study, conducted among young adults in the US military, vitamin D status was
      assessed by averaging multiple season-adjusted measures of 25-hydroxyvitamin D
      (25[OH]D). During an average of 5 years' follow-up, MS risk among healthy young
      adults with serum levels of 25(OH) vitamin D >100 nmol/l was about 60% lower than
      in individuals of the same age and sex with serum 25(OH) vitamin D levels <100
      nmol/l. If confirmed, these findings suggest that a high proportion of MS cases
      could be effectively prevented by vitamin D supplementation. Furthermore, there
      is growing evidence that vitamin D insufficiency is a risk factor for conversion
      from clinically isolated syndrome to MS and for MS progression. Both prevention
      and treatment trials with vitamin D are needed to confirm these findings and to
      determine optimal levels of vitamin D. 

PMID- 24289837
TI  - Decoding multiple sclerosis: an update on genomics and future directions.
AB  - A wealth of data confirms that genetic variation is an important determinant of
      multiple sclerosis (MS) risk. Population, family and molecular studies provide
      strong empirical support for a polygenic model of inheritance, driven primarily
      by allelic variants relatively common in the general population. The major
      histocompatibility complex (MHC) in chromosome 6p21.3 represents by far the
      strongest MS susceptibility locus genome-wide and was unambiguously identified in
      all studied populations. The primary signal arises from the HLA-DRB1 gene in the
      Class II segment of the locus, with hierarchical allelic and haplotypic effects.
      Independent protective signals in the telomeric Class I region of the locus have
      been described as well. Over the last 6 years, large multicenter DNA collections
      have thrived and the development of new laboratory and analytical approaches has
      matured at a remarkable pace, allowing pursuit of comprehensive 'agnostic' genome
      wide association studies to identify and characterise the non-MHC genetic
      component of MS. Taken together, the results have provided unambiguous evidence
      for the association of over 100 non-MHC loci with disease susceptibility. Follow
      up experiments refined some of the association signals (IL2RA and CD58),
      identified gene-gene interactions (HLA-DRB1/EVI5) and revealed mechanistic
      insights into the functional consequences of the identified gene variants, most
      notably an increase in the soluble to membrane-bound ratio for IL-7, IL-2 and TNF
      receptors and a tyrosine-protein kinase 2-mediated immune deviation. These
      results significantly broaden our understanding of disease pathogenesis and
      permit, for the first time, modeling an individual's disease risk within the
      context of his or her familial history. Progress in identifying additional risk
      alleles is likely to be rapid in the near future. Although the effect of any
      given predisposing variant is modest, the possibility exists that multifaceted
      gene-gene and/or gene-environment interactions could substantially increase the
      contribution of some variants to the overall genetic risk. In addition,
      susceptibility genes may be subject to epigenetic modifications, which greatly
      increase the complexity of MS inheritance. Despite these remarkable advances, the
      knowledge of MS genetics remains incomplete. For example, a key but unresolved
      question is whether genetic variants influence disease trajectory. Ongoing
      efforts to fully characterize the repertoire of genes that predispose to MS and
      modulate its presentation is discussed. Functional characterization of even a
      moderate genetic effect on MS pathogenesis by a known gene or group of genes can
      assist in elucidating fundamental mechanisms of disease expression and yield
      important therapeutic opportunities. 

PMID- 24289838
TI  - Measuring symptoms and wellness in the multiple sclerosis patient: issues in
      measurement.
AB  - Appropriate measurement of any state of health or disease depends on several
      factors. First and foremost is the scientific question to be answered, which can
      range from basic science to clinical processes to societal impact. Questions
      primarily address either the current state of the patient or are designed to
      measure change over time. Although it is sometimes possible to accomplish both
      objectives with one set of questions, this can be difficult and may not be
      appropriate. Questions must be designed appropriately to ensure reliability of
      the answer, validity of the concept being measured and the sensitivity or
      responsiveness of the measure to change. It is also becoming standard to evaluate
      all parameters for the clinical (or scientific) relevance of the measured value
      or change in value over time. The design of a measurement tool must consider the
      type of data to be collected, the difficulties in collecting complete data and
      the plan for data analysis. Ever-increasing computing power has provided novel
      approaches to analysis allowing for a broader range of measurement instruments.
      This review examines some important basic principles of measurement and considers
      issues as they apply to examples of measures used for patients with
      multisymptomatic illnesses such as multiple sclerosis, with a particular focus on
      application of the spasticity 0-10 Numerical Rating Scale and its correlation
      with the Patient Global Impression of Change scale. 

PMID- 24289839
TI  - Present and future of fMRI in multiple sclerosis.
AB  - Studies with functional MRI (fMRI) of the motor, visual and cognitive networks
      have consistently demonstrated functional cortical changes in the major multiple
      sclerosis (MS) clinical phenotypes. Compared with healthy subjects, these fMRI
      modifications are characterized by an altered recruitment of regions normally
      devoted to the performance of a given task, recruitment of additional areas,
      different resting state activity and disrupted connectivity. Studies that applied
      fMRI longitudinally have shown that such abnormalities vary over the course of
      the disease, not only after an acute relapse but also in clinically stable
      patients. fMRI and structural MRI abnormalities of the MS brain are correlated.
      Movement- and cognitive-associated fMRI changes were found to correlate with the
      amount of damage to brain normal-appearing white and gray matter and to the
      spinal cord. This suggests that, at least in some phases of the disease,
      increased recruitment of 'critical' central nervous system regions might
      contribute to limiting the functional impact of MS-related injury. fMRI has
      recently been applied to the assessment of functional modifications in the
      cervical cord of patients with MS. Evidence to date shows that cervical cord fMRI
      can reliably identify regions involved with tactile and proprioceptive
      stimulation in MS patients and different clinical phenotypes. As shown in brain
      studies, these investigations have detected increased recruitment in MS patients
      compared with healthy controls. At present, fMRI is a useful research tool, and
      reliable analysis and display methods have been developed. Future perspectives
      include development of fMRI paradigms for patients with MS-related disability and
      application of this technique in longitudinal studies to define the temporal
      evolution of functional cortical changes in different MS phenotypes as well as
      the effects of various therapeutic approaches on central nervous system
      plasticity.

PMID- 24289840
TI  - Health economic evaluation: why? When? How?
AB  - Advances in research and better understanding of the pathophysiology of diseases
      have resulted in an increase in the number of available health interventions that
      compete for finite public resources. Explicit choices must therefore be made
      about funding. 

PMID- 24289841
TI  - Can we optimize our teams? Multidisciplinary care for multiple sclerosis.
AB  - Established in 2003, the multiple sclerosis (MS) regional hospital network in the
      Auvergne area of France links not only neurologists but also many other
      specialists (e.g., urologists, ophthalmologists) and more than 400 other allied
      healthcare professionals (including physiotherapists, nurses, occupational
      therapists) involved in the care of patients with MS. This multidisciplinary
      network aims to improve quality of care for an estimated 1600 + MS patients in
      the Auvergne region through numerous training courses and medical support
      programs. The initiative is supported by the regional regulatory authority and
      receives public funding from the Auvergne regional state health insurance office.
      The Auvergne MS network has facilitated improvements in quality of care by
      coordinating patient care in the proximal vicinity of the patient's home and has
      provided useful information about MS epidemiology (incidence and prevalence) in
      the region. Using a multidisciplinary approach, the Auvergne MS network has
      explored other avenues of domiciliary-based care to seek improvements in the
      patient-centered management of MS. These include: access to high-dose
      methylprednisolone in the home, ensuring appropriate supervision and support;
      participation in national clinical research programs coordinated from hospital
      centers of excellence; provision of multidisciplinary clinic services where
      healthcare professionals across different disciplines can attend to the patient
      on the same day in the same center of care; development of individual and group
      based cognitive therapy programs; educational programs focusing on the management
      of fatigue and cognitive impairment associated with MS; and educational programs
      focusing on optimal use of immunomodulating agents in MS patients. 

PMID- 24289842
TI  - Multiple sclerosis spasticity epidemiology--key publications.
AB  - Summary of key publications presented at the poster session of the MS Experts'
      Summit. 

PMID- 24289843
TI  - Multiple sclerosis spasticity management--key publications.

PMID- 24289844
TI  - Advances in the management of multiple sclerosis spasticity: experiences from
      recent studies and everyday clinical practice.
AB  - Although spasticity of varying severity affects up to 80% of patients with
      multiple sclerosis (MS) during the course of their disease, the symptom is often
      overlooked and undertreated. Despite the availability of oral antispasticity
      treatments (baclofen, tizanidine and others), approximately one-third of MS
      patients in Europe and the USA experience moderate or severe nonfocalized
      spasticity. At present, a thorough clinical evaluation of MS-related spasticity
      that takes into account the patient's own perception of spasms, spasticity
      related pain and other associated symptoms is not common in daily neurological
      practice. Some of the usual spasticity scales, such as the Ashworth and modified
      Ashworth scales, reflect the observer's measurement of spasticity at a particular
      point in time. Herbal (smoked) cannabis has long been recognized as a possible
      option for relief of spasticity and neuropathic pain, but pertinent concerns
      about psychoactive effects and addiction risk have prevented its common use. An
      innovative method of benefiting from the mode of action of cannabinoids while
      limiting their drawbacks is to reduce peak plasma levels of 9-delta
      tetrahydrocannabinol and counteract psychoactivity with higher than naturally
      occurring proportions of a second cannabinoid, cannabidiol. Sativex(r) oromucosal
      spray (1:1 ratio of 9-delta-tetrahydrocannabinol/cannabidiol) has recently been
      approved in a number of EU countries and elsewhere for use in patients with MS
      related spasticity who are resistant to treatment with other antispasticity
      medications. In clinical trials, Sativex provided initial relief of spasticity
      symptoms within the first 4 weeks of treatment (trial period) in up to about half
      of patients resistant to other available oral antispasticity medications and
      demonstrated clinically significant improvement in spasticity (30% or higher
      reduction from baseline) in three-quarters of the initial responders. Adverse
      events were limited mainly to mild or moderate cases of somnolence and dizziness.
      Under everyday clinical practice conditions, Sativex at a mean daily dose of <7
      sprays/day, was shown to relieve spasticity in about 70% of patients previously
      resistant to treatment. Clear improvements were also noted in associated symptoms
      such as sleep disturbances, bladder problems, loss of mobility and cramps. In
      large observational studies, >80% of patients reported no adverse events with the
      use of Sativex and interim data from safety registries in the UK and Spain
      indicate a low risk for serious adverse drug reactions. Follow-up studies in
      Sativex responders support continued benefit without the need to increase doses
      for at least 1 year. Sativex appears to be a promising solution for a meaningful
      proportion of patients with MS-related spasticity who have inadequate response to
      current antispasticity medications. 

PMID- 24289845
TI  - Advances in the management of multiple sclerosis spasticity: multiple sclerosis
      spasticity guidelines.
AB  - Symptomatic therapy of multiple sclerosis (MS) is an important part of a
      comprehensive treatment plan that aims to improve patients' quality of life. In
      the current era of medical progress, several factors have led to the development
      of guidelines for MS management. There is continued need for an evidence-based
      approach supported by high-quality data from controlled clinical trials. Most
      healthcare systems require this approach and include it in the reimbursement
      process. Guidelines are usually committed by national or continental neurological
      societies. The Spanish Society of Neurology demyelinating diseases working group
      has developed a consensus document on spasticity in patients with MS. MS experts
      from the group used the metaplan method to sum up the most important
      recommendations about spasticity for inclusion in the guidance. Recommendations
      were classified according to the Scottish Intercollegiate Guidelines Network
      system and approved by all members of the group. In Germany, the guideline panel
      of the German Neurological Society endorsed the national competence network for
      multiple sclerosis (Krankheitsbezogenes Kompetenznetz Multiple Sklerose) to
      update the existing recommendations. The most recent fifth edition of the
      guidelines (dated April 2012) now also includes recommendations for treatment of
      key symptoms such as spasticity. More than 30 MS neurologists contributed to the
      new edition reflecting the need for broad expertise. After a first round in which
      key topics were defined, a web-based decision process was undertaken to further
      develop individual topics such as symptomatic therapy. The draft manuscript was
      reviewed once again by the group prior to submission to the official review
      process. The aims of spasticity treatment are to improve mobility and dexterity,
      achieve physiological movement patterns, reduce pain, facilitate nursing measures
      and avoid complications such as contractures. Representative antispasticity
      medications include baclofen, tizanidine, gabapentin, dantrolene, tolperisone,
      benzodiazepines and Sativex(r) oromucosal spray. Botulinum toxin and intrathecal
      baclofen may also be required in selected cases. Plans are currently in motion to
      develop next-level European guidelines through a concerted approach coordinated
      by the European Federation of Neurological Societies. 

PMID- 24289846
TI  - Clinical case reviews in multiple sclerosis spasticity: experiences from around
      Europe.
AB  - Spasticity is one of the main symptoms associated with multiple sclerosis (MS).
      Epidemiological studies indicate that approximately two-thirds of MS patients
      experience spasticity and, in a relevant proportion of this group, spasticity is
      moderate to severe. Yet, spasticity remains largely undertreated. The most
      commonly used oral antispasticity agents (e.g., baclofen, tizanidine, gabapentin)
      generally do not reduce spasticity adequately at dosages that are well tolerated
      by patients. This review of MS spasticity cases from around Europe presents
      current knowledge of considerations for administration of a new agent
      (tetrahydrocannabinol/cannabidiol-based nabiximols [Sativex(r)] oromucosal spray)
      for management of MS spasticity, with the aim of ensuring appropriate and optimal
      use for best outcomes. Assessment of the European clinical experience is intended
      to provide a better understanding of the prescribing regulations for MS
      spasticity treatments, facilitate identification of suitable candidate patients
      for Sativex and increase awareness of alternative management approaches for MS
      related spasticity. 

PMID- 24289847
TI  - Changing our culture to advance patient safety: the 2013 AANS Presidential
      Address.
AB  - "Changing our culture to advance patient safety" served as the theme of the 81st
      Annual Meeting of the American Association of Neurological Surgeons and is an
      issue of personal importance to the author. To improve outcomes for patients and
      prevent avoidable surgical errors, neurosurgeons must change the culture that
      currently exists in the operating room so that safety concerns are of the utmost
      importance and that each member of the care team has a personal sense of
      accountability. Doing this will involve implementing and consistently applying
      systems-based strategies to ensure an adequate level of safeguards; improving
      communication with all members of the care team and dismantling authority
      gradients; and maintaining a well-trained and well-rested workforce. 

PMID- 24289850
TI  - Aldosterone testing: evaluation of a novel automated immunoassay.
AB  - Aldosterone levels are increased in primary aldosteronism (PA) and might be
      triggered in several cardiovascular disorders. The aim of our study was to assess
      the analytical validity of a novel automated aldosterone immunoassay. Method
      comparison was also performed with a reference radioimmunoassay. We report for
      the first time the analytical validity of the LIAISON(r) aldosterone automated
      immunoassay. Such automated assay might therefore facilitate the screening of PA
      and risk stratification of cardiovascular diseases.

PMID- 24289851
TI  - Chain reaction mechanism in hydrogen/fluorine combustion.
AB  - Vibrationally excited species have been considered to play significant roles in
      H2/F2 reaction systems. In the present study, in order to obtain further
      understanding of the chain reaction mechanism in the combustion of mixtures
      containing H2 and F2, burning velocities for H2/F2/O2/N2 flames were measured and
      compared to that obtained from kinetic simulations using a detailed kinetic
      model, which involves the vibrationally excited species, HF(nu) and H2(nu), and
      the chain-branching reactions, HF(nu > 2) + F2 = HF + F + F (R1) and H2(nu = 1) +
      F2 = HF + H + F (R2). The results indicated that reaction R1 is not responsible
      for chain branching, whereas reaction R2 plays a dominant role in the chain
      reaction mechanism. The kinetic model reproduced the experimental burning
      velocities with the presumed rate constant of k2 = 6.6 * 10(-10) exp(-59 kJ mol(
      1)/RT) cm(3) s(-1) for R2. The suggested chain-branching reaction was also
      investigated by quantum chemical calculations at the MRCI-F12+CV+Q/cc-pCVQZ-F12
      level of theory. 

PMID- 24289849
TI  - The inhibitory role of Mir-29 in growth of breast cancer cells.
AB  - Mir-29 microRNA families are involved in regulation of various types of cancers.
      Although Mir-29 was shown to play an inhibitory role in tumorigenesis, the role
      of Mir-29 in breast cancer still remains obscure. In this study, we showed that
      Mir-29a is the dominant isoform in its family in mammary cells and expression of
      Mir-29a was down-regulated in different types of breast cancers. Furthermore,
      over-expression of Mir-29a resulted in significant slower growth of breast cancer
      cells and caused higher percentage of cells at G0/G1 phase. Consistent with this
      over-expression data, knockdown of Mir-29a in normal mammary cells lead to higher
      cell growth rate, and higher percentage of cells entering S phase. We further
      found that Mir-29a negatively regulated expression of B-Myb, which is a
      transcription factor associated with tumorigenesis. The protein levels of Cyclin
      A2 and D1 are consistent with the protein level of B-Myb. Taken together, our
      data suggests Mir-29a plays an important role in inhibiting growth of breast
      cancer cells and arresting cells at G0/G1 phase. Our data also suggests that Mir
      29a may suppress tumor growth through down-regulating B-Myb. 

PMID- 24289848
TI  - Beyond pain in fibromyalgia: insights into the symptom of fatigue.
AB  - Fatigue is a disabling, multifaceted symptom that is highly prevalent and
      stubbornly persistent. Although fatigue is a frequent complaint among patients
      with fibromyalgia, it has not received the same attention as pain. Reasons for
      this include lack of standardized nomenclature to communicate about fatigue, lack
      of evidence-based guidelines for fatigue assessment, and a deficiency in
      effective treatment strategies. Fatigue does not occur in isolation; rather, it
      is present concurrently in varying severity with other fibromyalgia symptoms such
      as chronic widespread pain, unrefreshing sleep, anxiety, depression, cognitive
      difficulties, and so on. Survey-based and preliminary mechanistic studies
      indicate that multiple symptoms feed into fatigue and it may be associated with a
      variety of physiological mechanisms. Therefore, fatigue assessment in clinical
      and research settings must consider this multi-dimensionality. While no clinical
      trial to date has specifically targeted fatigue, randomized controlled trials,
      systematic reviews, and meta-analyses indicate that treatment modalities studied
      in the context of other fibromyalgia symptoms could also improve fatigue. The
      Outcome Measures in Rheumatology (OMERACT) Fibromyalgia Working Group and the
      Patient Reported Outcomes Measurement Information System (PROMIS) have been
      instrumental in propelling the study of fatigue in fibromyalgia to the forefront.
      The ongoing efforts by PROMIS to develop a brief fibromyalgia-specific fatigue
      measure for use in clinical and research settings will help define fatigue, allow
      for better assessment, and advance our understanding of fatigue.

PMID- 24289853
TI  - Re: validation of a cell-cycle progression gene panel to improve risk
      stratification in a contemporary prostatectomy cohort.

PMID- 24289852
TI  - Depression is more than the sum score of its parts: individual DSM symptoms have
      different risk factors.
AB  - BACKGROUND: For diagnostic purposes, the nine symptoms that compose the DSM-5
      criteria for major depressive disorder (MDD) are assumed to be interchangeable
      indicators of one underlying disorder, implying that they should all have similar
      risk factors. The present study investigates this hypothesis, using a population
      cohort that shifts from low to elevated depression levels. METHOD: We assessed
      the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire;
      PHQ-9) and seven depression risk factors (personal and family MDD history, sex,
      childhood stress, neuroticism, work hours, and stressful life events) in a
      longitudinal study of medical interns prior to and throughout internship (n =
      1289). We tested whether risk factors varied across symptoms, and whether a
      latent disease model could account for heterogeneity between symptoms. RESULTS:
      All MDD symptoms increased significantly during residency training. Four risk
      factors predicted increases in unique subsets of PHQ-9 symptoms over time
      (depression history, childhood stress, sex, and stressful life events), whereas
      neuroticism and work hours predicted increases in all symptoms, albeit to varying
      magnitudes. MDD family history did not predict increases in any symptom. The
      strong heterogeneity of associations persisted after controlling for a latent
      depression factor. CONCLUSIONS: The influence of risk factors varies
      substantially across DSM depression criterion symptoms. As symptoms are
      etiologically heterogeneous, considering individual symptoms in addition to
      depression diagnosis might offer important insights obfuscated by symptom sum
      scores.

PMID- 24289854
TI  - Re: overdiagnosis and overtreatment in cancer: an opportunity for improvement.

PMID- 24289855
TI  - Re: use of advanced treatment technologies among men at low risk of dying from
      prostate cancer.

PMID- 24289856
TI  - Re: long-term outcomes of patients with lymph node metastasis treated with
      radical prostatectomy without adjuvant androgen-deprivation therapy.

PMID- 24289857
TI  - Re: clinical efficacy, safety and tolerability of collagenase clostridium
      histolyticum for the treatment of peyronie disease in 2 large double-blind,
      randomized, placebo controlled phase 3 studies.

PMID- 24289858
TI  - Re: the impact of mechanical bowel preparation on postoperative complications for
      patients undergoing cystectomy and urinary diversion.

PMID- 24289859
TI  - MicroRNA-183 suppresses retinoblastoma cell growth, invasion and migration by
      targeting LRP6.
AB  - Our study demonstrates the downregulation of microRNA-183 (miR-183) in
      retinoblastoma (RB) tissues and RB cell lines compared with normal retinal
      tissues. The ectopic expression of miR-183 in the RB cell lines Y79, SO-RB50 and
      WERI-RB1 suppresses cell viability, migration and invasion. Furthermore, the Wnt
      co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) was
      identified as a new target of miR-183, and restoration of the expression of LRP6
      rescues the effects induced by miR-183 in RB cells. These results indicate that
      miR-183 targets and downregulates LRP6 in the growth, migration and invasion of
      RB cells.

PMID- 24289860
TI  - A network approach to response inhibition: dissociating functional connectivity
      of neural components involved in action restraint and action cancellation.
AB  - The ability to inhibit action tendencies is vital for adaptive human behaviour.
      Various paradigms are supposed to assess action inhibition and are often used
      interchangeably. However, these paradigms are based on different
      conceptualizations (action restraint vs. action cancellation) and the question
      arises as to what extent different conceptualizations of inhibitory processing
      are mirrored in a distinct neural activation pattern. We used functional magnetic
      resonance imaging to investigate the neural correlates of action restraint vs.
      action cancellation. Analyses of local activity changes as well as network
      connectivity measures revealed a strong overlap of activation within a common
      action inhibition network including inferior frontal, pre-supplementary motor and
      thalamic brain areas as well as the anterior cingulate cortex. Furthermore, our
      findings pointed to additional neural networks that are distinct for action
      restraint (i.e. right superior frontal gyrus, left middle frontal gyrus, and
      bilateral anterior cingulate cortex) and action cancellation (i.e. right middle
      frontal gyrus, posterior cingulate cortex, and parietal regions). Our
      connectivity analyses showed that different inhibitory modalities largely relied
      on a task-independent global inhibition network within the brain. Furthermore,
      they suggested that the conceptually distinct inhibitory aspects of action
      restraint vs. action cancellation also activated additional specific brain
      regions in a task-dependent manner. This has implications for the choice of tasks
      in an empirical setting, but is also relevant for various clinical contexts in
      which inhibition deficits are considered a diagnostic feature. 

PMID- 24289862
TI  - The Portuguese adaptation of the Gudjonsson Suggestibility Scale (GSS1) in a
      sample of inmates.
AB  - This paper comprises two studies which address the validity of the Portuguese
      adaptation of the Gudjonsson Suggestibility Scale, GSS1. In study 1, the means
      and standard deviations for the suggestibility results of a sample of Portuguese
      inmates (N=40, Mage=37.5 years, SD=8.1) were compared to those of a sample of
      Icelandic inmates (Gudjonsson, 1997; Gudjonsson & Sigurdsson, 1996). Portuguese
      inmates' results were in line with the original results. In study 2, the means
      and standard deviations for the suggestibility results of the sample of
      Portuguese inmates were compared to those of a general Portuguese population
      sample (N=57, Mage=36.1 years, SD=12.7). The forensic sample obtained
      significantly higher scores in suggestibility measures than the general
      population sample. ANOVA confirmed that the increased suggestibility in the
      inmates sample was due to the limited memory capacity of this latter group. Given
      that the results of both studies 1 and 2 are in keeping with the author's
      original results (Gudjonsson, 1997), this may be regarded as a confirmation of
      the validity of the Portuguese GSS1.

PMID- 24289863
TI  - When benefitting a patient increases the risk for harm for third persons - the
      case of treating pedophilic Parkinsonian patients with deep brain stimulation.
AB  - This paper investigates the question whether it is ethically justified to treat
      Parkinsonian patients with known or suspected pedophilia with deep brain
      stimulation - given increasing evidence that this treatment might cause impulse
      control disorders, disinhibition, and hypersexuality. This specific question is
      not as exotic as it looks at a first glance. First, the same issue is raised for
      all other types of sexual orientation or behavior which imply a high risk for
      harming other persons, e.g. sexual sadism. Second, there are also several
      (psychotropic) drugs as well as legal and illegal leisure drugs which bear severe
      risks for other persons. We show that Beauchamp and Childress' biomedical ethics
      fails to derive a veto against medical interventions which produce risks for
      third persons by making the patients dangerous to others. Therefore, our case
      discussion reveals a blind spot of the ethics of principles. Although the first
      intuition might be to forbid the application of deep brain stimulation to
      pedophilic patients, we argue against such a simple way out, since in some
      patients the reduction of dopaminergic drugs allowed by deep brain stimulation of
      the nucleus subthalamicus improves impulsive control disorders, including
      hypersexuality. Therefore, we propose a strategy consisting of three steps: (1)
      risk assessment, (2) shared decision-making, and (3) risk management and
      safeguards. 

PMID- 24289861
TI  - Viral subversion of nucleocytoplasmic trafficking.
AB  - Trafficking of proteins and RNA into and out of the nucleus occurs through the
      nuclear pore complex (NPC). Because of its critical function in many cellular
      processes, the NPC and transport factors are common targets of several viruses
      that disrupt key constituents of the machinery to facilitate viral replication.
      Many viruses such as poliovirus and severe acute respiratory syndrome (SARS)
      virus inhibit protein import into the nucleus, whereas viruses such as influenza
      A virus target and disrupt host mRNA nuclear export. Current evidence indicates
      that these viruses may employ such strategies to avert the host immune response.
      Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate
      transport of viral RNAs. As viral proteins interact with key regulators of the
      host nuclear transport machinery, viruses have served as invaluable tools of
      discovery that led to the identification of novel constituents of nuclear
      transport pathways. This review explores the importance of nucleocytoplasmic
      trafficking to viral pathogenesis as these studies revealed new antiviral
      therapeutic strategies and exposed previously unknown cellular mechanisms.
      Further understanding of nuclear transport pathways will determine whether such
      therapeutics will be useful treatments for important human pathogens. 

PMID- 24289865
TI  - The maintenance of pulp health 17 years after root fracture in a maxillary
      incisor illustrating the diagnostic benefits of cone bean computed tomography.
AB  - AIM: To demonstrate the maintenance of pulp health in a tooth with a fractured
      root without any complications or endodontic treatment and the advantage of cone
      bean computed tomography (CBCT) compared with traditional radiographs in the
      diagnosis of root fractures. SUMMARY: The horizontal fracture of a maxillary
      central incisor is described that was an incidental finding on a routine
      radiographic examination 17 years after trauma. The tooth was asymptomatic. Intra
      oral radiography revealed a complicated multiple root fracture with separation of
      the root fragments, which was not confirmed by CBCT. This case report illustrates
      spontaneous healing of root fracture and the reparative potential in the area of
      root fracture including preservation of pulp health and also demonstrates that
      CBCT is a more reliable imaging technique than conventional radiographs regarding
      root fracture diagnosis. KEY LEARNING POINTS: The dental pulp is characterized by
      the ability to heal spontaneously in cases of root fracture. CBCT has advantages
      in diagnosing root fractures over intra-oral radiographs. CBCT should be employed
      with caution due to its increased radiation dose compared with periapical
      radiography.

PMID- 24289864
TI  - Pathways systematically associated to Hirschsprung's disease.
AB  - Despite it has been reported that several loci are involved in Hirschsprung's
      disease, the molecular basis of the disease remains yet essentially unknown. The
      study of collective properties of modules of functionally-related genes provides
      an efficient and sensitive statistical framework that can overcome sample size
      limitations in the study of rare diseases. Here, we present the extension of a
      previous study of a Spanish series of HSCR trios to an international cohort of
      162 HSCR trios to validate the generality of the underlying functional basis of
      the Hirschsprung's disease mechanisms previously found. The Pathway-Based
      Analysis (PBA) confirms a strong association of gene ontology (GO) modules
      related to signal transduction and its regulation, enteric nervous system (ENS)
      formation and other processes related to the disease. In addition, network
      analysis recovers sub-networks significantly associated to the disease, which
      contain genes related to the same functionalities, thus providing an independent
      validation of these findings. The functional profiles of association obtained for
      patients populations from different countries were compared to each other. While
      gene associations were different at each series, the main functional associations
      were identical in all the five populations. These observations would also explain
      the reported low reproducibility of associations of individual disease genes
      across populations. 

PMID- 24289866
TI  - Association between healthcare water systems and Pseudomonas aeruginosa
      infections: a rapid systematic review.
AB  - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen with a particular
      propensity to cause disease in the immunocompromised. Water systems have been
      reported to contribute to P. aeruginosa transmission in healthcare settings. AIM:
      To systematically assess the evidence that healthcare water systems are
      associated with P. aeruginosa infection; to review aspects of design that can
      increase their potential to act as a reservoir; and to compare the efficacy of
      strategies for eradicating contamination and preventing infection. METHODS: A
      rapid review methodology with a three-step search strategy was used to identify
      published studies. Scientific advisors were used to identify unpublished studies.
      FINDINGS: Twenty-five relevant studies were included. There was plausible
      evidence of transmission of P. aeruginosa from water systems to patients and vice
      versa, although no direct evidence to explain the exact mode of transfer. Two
      studies provided plausible evidence for effective interventions: point-of-use
      filters and increasing chlorine disinfection. Non-touch taps and aspects of water
      system design were identified as probable risk factors for P. aeruginosa biofilm
      formation and subsequent transmission to patients. Poor hand hygiene or
      compliance with contact precautions were identified as potential contributory
      factors; plausible evidence to confirm this was not available. CONCLUSIONS: Water
      systems can act as a source of P. aeruginosa infection in healthcare settings,
      although the route of transmission is unclear. Contamination appears to be
      confined to the distal ends of a water system and can persist for prolonged
      periods. Further studies are required to establish effective methods of
      preventing transmission and eradicating P. aeruginosa from plumbing systems.

PMID- 24289867
TI  - Seminal PDC-109 protein vis-a-vis cholesterol content and freezability of buffalo
      spermatozoa.
AB  - Advancements in reproductive technologies have shown seminal plasma (SP) as a
      nutritive-protective medium for spermatozoa metabolism, function and transport.
      At the same time quality variables and thus freezability of spermatozoa are
      influenced by SP proteins originating from male reproductive tract. One such
      protein, viz. PDC-109 is reported to influence freezability of spermatozoa in
      cattle. Thus the present investigation was designed to evaluate effect of seminal
      PDC-109 protein concentration on post-thaw cholesterol content and semen quality
      variables (SQP) as an indicator of membrane integrity and freezability,
      respectively of buffalo spermatozoa. Ejaculates (n=42) selected on the basis of
      mass activity and individual motility were divided into three parts, first part
      for SP proteins isolation, second for cholesterol estimation and third part was
      cryo-preserved to evaluate freezability based on post-thaw SQP, viz. individual
      progressive motility, viability and acrosome integrity of spermatozoa. A total of
      28 (66.7%) and 14 (33.3%) ejaculates from four bulls were found as freezable or
      non-freezable, respectively. Though total seminal plasma protein (TSPP)
      concentration was found similar in freezable and non-freezable ejaculates, the
      heparin binding proteins (HBP) content in non-freezable semen was greater
      (P<0.01) than freezable ejaculates. There was a similar trend for the PDC-109
      protein content in respective ejaculates. Cholesterol content of spermatozoa and
      SQP were greater (P<0.05 and 0.01, respectively) in freezable as compared to non
      freezable ejaculates of each bull at post-thaw stage. This study showed that
      concentrations of HBP and PDC-109 in non-freezable semen might be responsible for
      greater cryo-damage reflecting in poor freezability of buffalo spermatozoa. 

PMID- 24289868
TI  - Validation of a recombinant human bactericidal/permeability-increasing protein
      (hBPI) expression vector using murine mammary gland tumor cells and the early
      development of hBPI transgenic goat embryos.
AB  - Human bactericidal/permeability-increasing protein (hBPI) is the only
      antibacterial peptide which acts against both gram-negative bacteria and
      neutralizes endotoxins in human polymorphonuclear neutrophils; therefore, hBPI is
      of great value in clinical applications. In the study, we constructed a hBPI
      expression vector (pBC1-Loxp-Neo-Loxp-hBPI) containing the full-length hBPI
      coding sequence which could be specifically expressed in the mammary gland. To
      validate the function of the vector, in vitro cultured C127 (mouse mammary
      Carcinoma Cells) were transfected with the vector, and the transgenic cell clones
      were selected to express hBPI by hormone induction. The mRNA and protein
      expression of hBPI showed that the constructed vector was effective and suitable
      for future application in producing mammary gland bioreactor. Then, female and
      male goat fibroblasts were transfected with the vector, and two male and two
      female transgenic clonal cell lines were obtained. Using the transgenic cell
      lines as nuclear donors for somatic cell nuclear transfer, the reconstructed goat
      embryos produced from all four clones could develop to blastocysts in vitro. In
      conclusion, we constructed and validated an efficient mammary gland-specific hBPI
      expression vector, pBC1-Loxp-Neo-Loxp-hBPI, and transgenic hBPI goat embryos were
      successfully produced, laying foundations for future production of recombinant
      hBPI in goat mammary gland. 

PMID- 24289869
TI  - [The transformation of cardiology in the twentieth century].

PMID- 24289870
TI  - Influence of osteotomy procedure and surgical experience on early complications
      after orthognathic surgery in the mandible.
AB  - INTRODUCTION: This study evaluated the influence of osteotomy procedure and
      surgical experience on early complication rates following orthognathic surgery in
      the mandible. MATERIALS AND METHODS: In a retrospective study, patients who
      underwent a mandibular osteotomy (Obwegeser-Dal Pont (ODP) and Hunsuk-Epker (HE))
      were included. Incidence of "bad splits", "bleeding episodes", "delayed wound
      healing", "failed osteosynthesis" and "nerve lesions" at 2 months post
      operatively were recorded. Surgical experience was classified as: beginner (<10),
      intermediate (10-40) and expert (>40). Complications were correlated to the
      surgical approach and the experience level of the surgeon. RESULTS: 400 patients
      were included. 200 underwent a bimaxillary approach. 186 patients were operated
      using the ODP technique, 214 according to HE. Multivariate analysis confirmed
      significantly more unwanted fractures and bleeding events for ODP when compared
      to HE (p = 0.28, p = 0.003). Experienced surgeons had more osteosynthesis
      failures (0.047) and significantly more nerve lesions than the other groups (p =
      0.01). DISCUSSION: The HE osteotomy showed a more reliable fracture mechanism
      with less relevant bleeding episodes. Differences between the surgeons of varying
      training status were marginal with exception of a higher rate of osteosynthesis
      failure and temporary hypoesthesia in the experienced group.

PMID- 24289871
TI  - Ultracision Harmonic Scalpel in oral and oropharyngeal cancer resection.
AB  - OBJECTIVE: The aim of this prospective study was to evaluate the benefits and
      risks when using an Ultracision Harmonic Scalpel in the surgical treatment of
      oral and oropharyngeal carcinomas. STUDY DESIGN: Prospective non-randomized.
      SETTING: Clinica Otorinolaringoiatrica, Azienda Ospedaliero-Universitaria.
      Trieste, Italy. SUBJECTS AND METHODS: In this study, conducted from April 2008 to
      August 2010, 36 consecutive patients underwent resection of oral or oropharyngeal
      carcinoma and lateral lymphadenectomy using the Ultracision Harmonic Scalpel.
      Evaluation criteria included length of the surgical procedure, intraoperative
      blood loss, quantity of neck drainage on the first, second and third
      postoperative days, postoperative complications, and a subjective assessment of
      postoperative pain and lymphatic oedema of the neck. Results were compared with
      previous surgical procedures carried out between May 2006 and March 2008 using
      cold knife and bipolar haemostasis (n = 36) when the Harmonic Scalpel was not
      available. RESULTS: In patients treated with the Harmonic Scalpel, operating time
      was significantly reduced, both for resection of the carcinoma and the lateral
      lymphadenectomy. Intraoperative blood loss and neck drainage on the first and
      second postoperative days were significantly less and pain scores were
      significantly lower than in the cold knife group. No postoperative complications
      were noted in the Harmonic Scalpel group. The only disadvantage noted in the
      Harmonic Scalpel group was the high incidence of lymphatic oedema of the neck.
      CONCLUSIONS: Use of the Harmonic Scalpel during resection of oral cancer and
      lateral lymphadenectomy is safe and confers some advantages over conventional
      methods.

PMID- 24289872
TI  - Development of the Greek version of the University of Washington quality of life
      questionnaire for patients with head and neck cancer.
AB  - The University of Washington quality of life (UW-QOL) questionnaire, created in
      1993 to evaluate health related quality of life, has been widely used in English
      speaking populations and translated and validated in other languages. The aim of
      the present study was to carefully translate and psychometrically validate the UW
      QOL questionnaire in Greek. The revised version of the questionnaire was obtained
      by forward and backward translation of the original English version, according to
      internationally accepted guidelines. Validation was performed in 120 patients
      with head and neck cancer treated in a Greek Anticancer Institute in Athens,
      during their follow-up visits. Eligible patients completed the Greek version of
      the questionnaire and two other previously validated quality of life
      questionnaires (EORTC QLQ H&N35 and C-30). Related data and the patients'
      demographics were extracted from the patient's notes. Strong internal consistency
      (mean Cronbach alpha value of 0.83) was shown, with good construct validity.
      Statistically significant differences were noted between tumour staging and
      treatment modality and global quality of life. Strong correlation was shown
      between previously validated EORTC questionnaires and the translated UW-QOL
      questionnaire. In conclusion, the Greek version of the UW-QOL questionnaire
      appears to be culturally appropriate and psychometrically valid.

PMID- 24289873
TI  - Histopathological grading systems and their relationship with clinical parameters
      in lower lip squamous cell carcinoma.
AB  - The objective of this study was to evaluate the histopathological grade of
      malignancy in a series of lower lip squamous cell carcinomas (LLSCCs) using three
      histopathological grading systems (invasive front grading system, World Health
      Organization (WHO) grading system, and histological risk assessment), and to
      correlate this with clinical parameters (tumour size/extent, regional lymph node
      metastasis, and clinical stage). Haematoxylin-eosin-stained histological sections
      obtained from 59 cases of LLSCC were analyzed by light microscopy. Grading of the
      invasive tumour front showed a significant association between low grade of
      malignancy and the absence of regional lymph node metastasis (P=0.030) and
      initial clinical stage (P=0.043). No significant associations were observed
      between the clinical parameters analyzed and the WHO system (P>0.05). Using the
      risk assessment, a highly significant association was observed between the risk
      score and regional lymph node metastasis (P=0.004) and clinical stage (P=0.002).
      In addition, the lymphocytic infiltrate was significantly associated with
      regional lymph node metastasis (P=0.017) and clinical stage (P=0.040). The
      results of the present study suggest that, among the histopathological grading
      systems evaluated, the histological risk assessment is the best option to predict
      the biological behaviour of LLSCCs.

PMID- 24289874
TI  - Progression in attenuating myocardial reperfusion injury: an overview.
AB  - Reperfusion by means of percutaneous coronary intervention or thrombolytic
      therapy is the most effective treatment for acute myocardial infarction, markedly
      reducing mortality and morbidity. Reperfusion however induces necrotic and
      apoptotic damages to cardiomyocytes, that were viable prior to reperfusion, a
      process called lethal reperfusion injury. This process, consisting of many single
      processes, may be responsible of up to half of the final infarct size. A myriad
      of therapies as an adjunct to reperfusion have been studied with the purpose to
      attenuate reperfusion injury. The majority of these studies have been
      disappointing or contradicting, but recent proof-of-concept trials show that
      reperfusion injury still is a legitimate target. This overview will discuss these
      trials, the progression in attenuating myocardial reperfusion injury, promising
      therapies, and future perspectives. 

PMID- 24289875
TI  - Physical activity: from epidemiological evidence to individualized patient
      management.
AB  - BACKGROUND: Physical activity (PA), physical fitness (PF), and even a few
      sedentary behaviors (SB) are strongly and independently linked to improved
      survival rate. However, key questions remain: what are the physiological
      interrelationships between SB, PA, and PF? How should we differently emphasize
      promoting PA, increasing PF with exercise, and decreasing SB among other
      prevention measures? What are the interrelationships of both PA and SB levels
      with drug treatment efficacy? METHODS: To address these questions we developed an
      integrated patient-centric model combining physiology with epidemiological
      evidence to characterize the individual risk attached to PA level, PF, and SB.
      Epidemiological data were collected by extensive literature review. RESULTS: Nine
      meta-analyses, 198 cohort studies (3.8 million people), and 13 controlled trials
      were reviewed. 1. A high level of SB induces chronic stress and increases the
      risk of both chronic disease and mortality. 2. Vigorous PA increases PF and
      physiological reserve, thereby improving survival rate. This effect is not
      mediated by improved traditional risk factors. The risk for most individuals is a
      mix of high SB, low to mild PA, and low to mild PF. This model can improve the
      individualized prescription of PA modalities. Furthermore, the benefit of
      treatments such as statins or beta-blockers can be cancelled out if a decrease in
      PA or an increase in SB is induced by drug related side effects. CONCLUSIONS: To
      improve patient management both types of therapeutic interventions and dose
      should be carefully chosen for each individual in order to maintain/increase PA
      level while decreasing SB.

PMID- 24289876
TI  - Contemporary clinical outcomes of patients treated with or without rotational
      coronary atherectomy--an analysis of the UK central cardiac audit database.
AB  - INTRODUCTION: Rotational atherectomy (RA) is widely used for treating calcified
      coronary lesions. Clinical data however remain limited. METHODS: We assessed
      outcome and survival among patients undergoing percutaneous coronary intervention
      (PCI) with or without RA in the UK between September 2007 and March 2011.
      RESULTS: Data from 221,669 percutaneous coronary intervention (PCI) procedures
      were analysed; 2152 patients (0.97%) underwent RA (RA+); the remainder underwent
      conventional PCI (RA-). RA+ patients were older (71.7+/-9.6 vs. 64.1+/-12.8 year;
      p<0.001), and had a higher incidence of diabetes (26.4% vs. 18.0%; p<0.001),
      hypertension, (61.9% vs. 49.4%; p<0.001), peripheral vascular disease (9.9% vs.
      4.2%, p<0.001), cerebrovascular disease (5.5% vs. 3.4%, p<0.001), renal
      impairment (3.4% vs. 1.5%, p<0.001) and poor left ventricular function (11.4% vs.
      4.3%,p<0.001). Procedural success was lower among RA+ patients (90.3% vs 94.6%;
      p<0.001) and procedural complications were more frequent (9.7% vs 5.4%; p<0.001).
      After 2.4+/-1.2 years follow-up, unadjusted Cox proportional hazard modeling
      demonstrated poorer survival for RA+ patients (HR 2.21, 95%CI 1.97-2.49;
      p<0.0001). This disadvantage remained after adjustment for adverse variables (HR
      1.26, 95%CI 1.11-1.44; p=0.0004) and following propensity analysis. There was
      evidence however of improved survival for RA+ patients with left main stem
      disease (HR 0.52, 95%CI 0.35-0.75, p<0.0001), and peripheral vascular disease (HR
      0.65, 95%CI 0.43-0.98, p<0.0005). CONCLUSIONS: Rotational atherectomy was
      undertaken in patients with higher pre-procedural risk. Medium term survival was
      worse among patients undergoing rotational atherectomy, and this survival
      disadvantage remained after correction for available adverse factors. Rotational
      atherectomy however remains clinically useful for patients with calcified
      coronary lesions.

PMID- 24289878
TI  - Dimensional structure and course of post-traumatic stress symptomatology in World
      Trade Center responders.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) in response to the World Trade
      Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent
      and persistent health conditions among both professional (e.g. police) and non
      traditional (e.g. construction worker) WTC responders, even several years after
      9/11. However, little is known about the dimensionality and natural course of WTC
      related PTSD symptomatology in these populations. METHOD: Data were analysed from
      10 835 WTC responders, including 4035 police and 6800 non-traditional responders
      who were evaluated as part of the WTC Health Program, a clinic network in the New
      York area established by the National Institute for Occupational Safety and
      Health. Confirmatory factor analyses (CFAs) were used to evaluate structural
      models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL)
      panel regressions were used to examine the prospective interrelationships among
      PTSD symptom clusters at 3, 6 and 8 years after 9/11. RESULTS: CFAs suggested
      that five stable symptom clusters best represent PTSD symptom dimensionality in
      both police and non-traditional WTC responders. This five-factor model was also
      invariant over time with respect to factor loadings and structural parameters,
      thereby demonstrating its longitudinal stability. ARCL panel regression analyses
      revealed that hyperarousal symptoms had a prominent role in predicting other
      symptom clusters of PTSD, with anxious arousal symptoms primarily driving re
      experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional
      numbing symptoms over time. CONCLUSIONS: Results of this study suggest that
      disaster-related PTSD symptomatology in WTC responders is best represented by
      five symptom dimensions. Anxious arousal symptoms, which are characterized by
      hypervigilance and exaggerated startle, may primarily drive re-experiencing
      symptoms, while dysphoric arousal symptoms, which are characterized by sleep
      disturbance, irritability/anger and concentration difficulties, may primarily
      drive emotional numbing symptoms over time. These results underscore the
      importance of assessment, monitoring and early intervention of hyperarousal
      symptoms in WTC and other disaster responders.

PMID- 24289880
TI  - PARP inhibitors: current status and implications for anticancer therapeutics.
AB  - Poly(ADP-ribose) polymerases (PARPs) comprise of a large family of 17 proteins
      encoded by various genes which participate in genome maintenance, apoptosis,
      inflammatory responses and the regulation of gene expression programs. PARP
      inhibitors, as therapeutic agents, come into play acting on both PARP 1 and PARP
      2. These drugs seem to target tumor cells in a moment of vulnerability when they
      are undergoing DNA repair. In the past few years this class of anti-cancer drug
      has been discovered to show a promising niche in the clinic. 

PMID- 24289881
TI  - The effects of discharge to an intermediate care unit after a critical illness: a
      5-year cohort study.
AB  - PURPOSE: The impact of the intermediate care unit (IMCU) on post-intensive care
      unit (ICU) outcomes is controversial. MATERIALS AND METHODS: We analyzed
      admissions from January 2003 to December 2008 from a mixed ICU in a teaching
      hospital in Brazil with a high patient-to-nurse ratio (3.5:1 on the ICU, 11:1 on
      the IMCU, 20-25:1 on the ward). A retrospective propensity-matched analysis was
      performed with data from 690 patients who were discharged after at least 3 days
      of ICU stay. RESULTS: Of the 690 patients, 160 (23%) were discharged to the IMCU.
      A total of 399 propensity-matched patients were compared: 298 were discharged to
      the ward and 101 were discharged to the IMCU. Ninety-day mortality rate was
      similar between the IMCU and ward patients (22% vs 18%, respectively, P = .37),
      as was the unplanned ICU readmission rate (P = .63). In a multivariate logistic
      regression, discharge to the IMCU had no effect on the 90-day mortality rate (P =
      .27). CONCLUSIONS: In a resource-limited setting with a high patient-to-nurse
      ratio, discharge to IMCU had no impact on 90-day mortality rate and on unplanned
      readmission rate. The impact of discharge to the IMCU on the outcome for
      critically ill patients should be evaluated in further studies.

PMID- 24289879
TI  - Crystal structures of highly specific phosphinic tripeptide enantiomers in
      complex with the angiotensin-I converting enzyme.
AB  - Human somatic angiotensin-I converting enzyme (ACE) is a zinc-dependent
      dipeptidyl carboxypeptidase and a central component of the renin angiotensin
      aldosterone system (RAAS). Its involvement in the modulation of physiological
      actions of peptide hormones has positioned ACE as an important therapeutic target
      for the treatment of hypertension and cardiovascular disorders. Here, we report
      the crystal structures of the two catalytic domains of human ACE (N- and C-) in
      complex with FI, the S enantiomer of the phosphinic ACE/ECE-1 (endothelin
      converting enzyme) dual inhibitor FII, to a resolution of 1.91 and 1.85 A,
      respectively. In addition, we have determined the structure of AnCE (an ACE
      homologue from Drosophila melanogaster) in complex with both isomers. The
      inhibitor FI (S configuration) can adapt to the active site of ACE catalytic
      domains and shows key differences in its binding mechanism mostly through the
      reorientation of the isoxazole phenyl side group at the P1' position compared
      with FII (R configuration). Differences in binding are also observed between FI
      and FII in complex with AnCE. Thus, the new structures of the ACE-inhibitor
      complexes presented here provide useful information for further exploration of
      ACE inhibitor pharmacophores involving phosphinic peptides and illustrate the
      role of chirality in enhancing drug specificity.

PMID- 24289882
TI  - Characterizing critical care physician staffing in rural America: a description
      of Iowa intensive care unit staffing.
AB  - PURPOSE: This study aimed to characterize intensive care unit (ICU) physician
      staffing patterns in a predominantly rural state. MATERIALS AND METHODS: A
      prospective telephone survey of ICU nurse managers in all Iowa hospitals with an
      ICU was conducted. RESULTS: Of 122 Iowa hospitals, 64 ICUs in 58 (48%) hospitals
      were identified, and 46 (72%) responded to the survey. Most ICUs (96%) used an
      open admission model and cared for undifferentiated medical and surgical patients
      (88%), and only 27% of open ICUs required critical care or pulmonary consultation
      for admitted patients. Most (59%) Iowa ICUs had a critical care physician or
      pulmonologist available, and high-intensity staffing was practiced in 30% of
      ICUs. Most physicians identified as practicing critical care (63%) were not board
      certified in critical care. Critical care physicians were available in a minority
      of hospitals routinely for inpatient intubation and cardiac arrest management
      (29% and 10%, respectively), and emergency physicians and other practitioners
      commonly responded to emergencies throughout the hospital. CONCLUSIONS: Many Iowa
      hospitals have ICUs, and staffing patterns in Iowa ICUs mirror closely national
      staffing practices. Most ICUs are multispecialty, open ICUs in community
      hospitals. These factors should inform training and resource allocation for
      intensivists in rural states.

PMID- 24289883
TI  - Prediction models of prevalent radiographic vertebral fractures among older men.
AB  - No studies have compared how well different prediction models discriminate older
      men who have a radiographic prevalent vertebral fracture (PVFx) from those who do
      not. We used area under receiver operating characteristic curves and a net
      reclassification index to compare how well regression-derived prediction models
      and nonregression prediction tools identify PVFx among men age >=65 yr with
      femoral neck T-score of -1.0 or less enrolled in the Osteoporotic Fractures in
      Men Study. The area under receiver operating characteristic for a model with age,
      bone mineral density, and historical height loss (HHL) was 0.682 compared with
      0.692 for a complex model with age, bone mineral density, HHL, prior non-spine
      fracture, body mass index, back pain, grip strength, smoking, and glucocorticoid
      use (p values for difference in 5 bootstrapped samples 0.14-0.92). This complex
      model, using a cutpoint prevalence of 5%, correctly reclassified only a net 5.7%
      (p = 0.13) of men as having or not having a PVFx compared with a simple criteria
      list (age >= 80 yr, HHL >4 cm, or glucocorticoid use). In conclusion, simple
      criteria identify older men with PVFx and regression-based models. Future
      research to identify additional risk factors that more accurately identify older
      men with PVFx is needed.

PMID- 24289886
TI  - Influenza vaccinations: older adults' decision-making process.
AB  - The purpose of this study was to explore the self-perceived influences among
      older adults in deciding whether to take or not take the seasonal influenza
      vaccine. Thirty-one receivers and six non-receivers (aged 67-91) participated in
      six focus groups in London, Ontario. The focus group meetings lasted
      approximately 60 minutes, were digitally audio-recorded, and transcribed
      verbatim. Inductive content analysis was performed to analyse the transcripts.
      The major facilitators of taking the vaccine were recommendations by, and trust
      in, health professionals, and a belief in vaccine efficacy. The major barriers
      were a fear of adverse reactions and the belief in resilience of an older adult.
      The Canadian Public Health Agency and allied health professionals should educate
      older adults in accurate influenza symptoms, vaccine efficacy, and populations at
      risk for contracting influenza. Focus should be given on correcting
      misconceptions about adverse events.

PMID- 24289885
TI  - Immune activation promotes depression 1 month after diffuse brain injury: a role
      for primed microglia.
AB  - BACKGROUND: Traumatic brain injury (TBI) is associated with a higher incidence of
      depression. The majority of individuals who suffer a TBI are juveniles and young
      adults, and thus, the risk of a lifetime of depressive complications is a
      significant concern. The etiology of increased TBI-associated depression is
      unclear but may be inflammatory-related with increased brain sensitivity to
      secondary inflammatory challenges (e.g., stressors, infection, and injury).
      METHODS: Adult male BALB/c mice received a sham (n = 52) or midline fluid
      percussion injury (TBI; n = 57). Neuroinflammation, motor coordination (rotarod),
      and depressive behaviors (social withdrawal, immobility in the tail suspension
      test, and anhedonia) were assessed 4 hours, 24 hours, 72 hours, 7 days, or 30
      days later. Moreover, 30 days after surgery, sham and TBI mice received a
      peripheral injection of saline or lipopolysaccharide (LPS) and microglia
      activation and behavior were determined. RESULTS: Diffuse TBI caused
      inflammation, peripheral cell recruitment, and microglia activation immediately
      after injury coinciding with motor coordination deficits. These transient events
      resolved within 7 days. Nonetheless, 30 days post-TBI a population of deramified
      and major histocompatibility complex II(+) (primed) microglia were detected.
      After a peripheral LPS challenge, the inflammatory cytokine response in primed
      microglia of TBI mice was exaggerated compared with microglia of controls.
      Furthermore, this LPS-induced microglia reactivity 30 days after TBI was
      associated with the onset of depressive-like behavior. CONCLUSIONS: These results
      implicate a primed and immune-reactive microglial population as a possible
      triggering mechanism for the development of depressive complications after TBI.

PMID- 24289884
TI  - Sex differences in corticotropin-releasing factor receptor-1 action within the
      dorsal raphe nucleus in stress responsivity.
AB  - BACKGROUND: Women are twice as likely as men to suffer from stress-related
      affective disorders. Corticotropin-releasing factor (CRF) is an important link
      between stress and mood, in part through its signaling in the serotonergic dorsal
      raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of
      numerous clinical trials but has not yet been proven efficacious. We hypothesized
      that sex differences in CRFr1 modulation of DR circuits might be key determinants
      in predicting therapeutic responses and affective disorder vulnerability.
      METHODS: Male and female mice received DR infusions of the CRFr1 antagonist, NBI
      35965, or CRF and were evaluated for stress responsivity. Sex differences in
      indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR
      were examined. Whole-cell patch-clamp electrophysiology assessed sex differences
      in serotonin neuron membrane characteristics and responsivity to CRF. RESULTS:
      Males showed robust behavioral and hypothalamic-pituitary-adrenal axis responses
      to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive.
      Sex differences were also found for both CRF-induced DR cFos and CRFr1 co
      localization throughout the DR. Electrophysiologically, female serotonergic
      neurons showed blunted membrane excitability and divergent inhibitory
      postsynaptic current responses to CRF application. CONCLUSIONS: These studies
      demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted
      female responses to NBI 35965 and CRF suggest unique stress modulation of the DR.
      These sex differences might underlie affective disorder vulnerability and
      differential sensitivity to pharmacologic treatments developed to target the CRF
      system, thereby contributing to a current lack of CRFr1 antagonist efficacy in
      clinical trials.

PMID- 24289887
TI  - Safety and efficacy of recombinant human erythropoietin treatment of non-motor
      symptoms in Parkinson's disease.
AB  - BACKGROUND: Numerous animal studies and clinical trials have demonstrated that
      erythropoietin (EPO) has therapeutic effects in ischemic and degenerative
      diseases. However, few clinical trials have investigated the effect of EPO in
      Parkinson's disease (PD) patients. This study was an exploratory pilot study to
      investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor
      symptoms (NMS) in PD patients. METHODS: A total of 26 PD patients at the Hanyang
      University Hospital were enrolled in the study. The participants were randomly
      assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously
      (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated
      using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), the NMS Scale
      (NMSS) and the 39-Item Parkinson's Disease Questionnaire (PDQ-39). [(18)F] N-(3
      fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) photon
      emission tomography (PET) scanning was performed on each participant at baseline
      and again after 12 months. RESULTS: The rhEPO administration significantly
      improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects
      motor function, did not change significantly after the rhEPO treatment. With the
      NMSS, the domains of cardiovascular autonomic function, sleep/fatigue,
      mood/cognition and attention/memory showed significant changes. None of the
      participants experienced any serious adverse effects. DISCUSSION: We found that
      rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic
      refractory NMS, such as cardiovascular autonomic dysfunction and cognition,
      showed improvement after the administration of rhEPO. Our results suggest that
      rhEPO might be a good candidate for the treatment of NMS in PD patients.

PMID- 24289888
TI  - The coexistence of well- and ill-being in persons with multiple sclerosis, their
      caregivers and health professionals.
AB  - BACKGROUND: Studies on emotional distress and health-related quality of life
      (HRQOL) broadened the traditional bio-medical focus in MS research, but little
      attention was paid to general well-being indicators. OBJECTIVE: To investigate
      for the first time both ill-being and well-being dimensions in persons with MS
      (PwMSs), caregivers and health professionals, in relation to both health and life
      in general. METHODS: A multi-center study assessed participants' depression (Beck
      Depression Inventory-II), HRQOL (Short Form-36), psychological well-being
      (Psychological Well-Being Scales), optimal experience (Flow Questionnaire), life
      satisfaction (Satisfaction with Life Scale), hedonic balance (Positive Affect and
      Negative Affect Schedule). Demographic and clinical information was also
      gathered. RESULTS: Overall, 71 PwMSs, 71 caregivers and 26 professionals were
      enrolled (N=168). Compared to healthy populations, PwMSs reported higher
      depression, lower HRQOL and lower general well-being; caregivers presented higher
      depression and lower general well-being; professionals reported the best ill- and
      well-being profiles. However, after controlling for demographic differences in
      age and education, hierarchical regressions highlighted that, though PwMSs
      reported higher depression and lower HRQOL than caregivers and professionals,
      their general well-being substantially leveled off. CONCLUSIONS: Well-being
      coexists with ill-being. It can counterbalance the negative effects of disease or
      caregiving, and its measurement could complement and support medical
      intervention.

PMID- 24289889
TI  - Clinical features in Guillain-Barre syndrome with anti-Gal-C antibody.
AB  - INTRODUCTION: Guillain-Barre syndrome (GBS) has often been associated with
      antibodies to glycolipids, such as galactocerebroside (Gal-C), a component of
      myelin. Whether patients who have GBS with anti-Gal-C antibody (Gal-C-GBS) more
      often have demyelinating neuropathy or axonal neuropathy remains controversial.
      Their clinical features have also been unestablished. METHODS: We enrolled 47
      patients with Gal-C-GBS. Their clinical and electrophysiological data were
      retrospectively reviewed and compared to 119 patients with GBS without anti-Gal-C
      antibody (non-Gal-C-GBS). RESULTS: Demyelinating polyneuropathy occurred 4 times
      more frequently than axonal polyneuropathy in patients with Gal-C-GBS, but
      without statistical significance compared to patients with non-Gal-C-GBS (2.2:1).
      Patients with Gal-C-GBS had more frequent sensory deficits, autonomic
      involvements, and antecedent Mycoplasma pneumoniae (MP) infection than patients
      with non-Gal-C-GBS. CONCLUSIONS: This is the largest study clarifying the
      clinical and electrophysiological findings that more frequent sensory deficits,
      autonomic involvements, and antecedent MP infection are associated with Gal-C
      GBS.

PMID- 24289890
TI  - Quantitative analysis of brainstem atrophy on magnetic resonance imaging in
      chronic progressive neuro-Behcet's disease.
AB  - OBJECTIVES: To examine whether quantitative analysis of the brainstem areas on
      magnetic resonance imaging (MRI) scans is useful for diagnosis as well as
      evaluation of disease activity in chronic progressive neuro-Behcet's disease
      (CPNB). METHODS: MRI scans in patients with acute neuro-Behcet's disease (ANB) (n
      = 10), CPNB (n = 10), Behcet's disease with neurological manifestations non
      attributable to NB (non-NB) (n = 8), and control patients with non-inflammatory
      neurological diseases (NID) (n = 10) were studied. The areas of midbrain
      tegmentum and pons were measured on mid-sagittal sections of T1-weighted images
      of MRI using software NIH Image J ver.1.45. RESULTS: The areas of midbrain
      tegmentum as well as those of pons were significantly decreased in CPNB compared
      with those in the other three groups. On receiver operating characteristic (ROC)
      analysis, the sensitivity and specificity of the areas of brainstem combining
      midbrain tegmentum and pons for diagnosis of CPNB against non-CPNB (ANB+non-NB)
      were 80.0% and 94.4%, respectively, at cut-off value of 614.9 mm(2). Brainstem
      atrophy progressed most markedly during the first 2 years during the course of
      CPNB. Moreover, the progression rate of atrophy was closely correlated with the
      elevation of cerebrospinal fluid interleukin-6. CONCLUSION: These results
      indicate that quantitative analysis of the brainstem areas on MRI scans is
      effective for diagnosis as well as for evaluation of the disease activity in
      CPNB. Moreover, it is suggested that an appropriate therapeutic intervention to
      reduce CSF IL-6 would be required as early as possible upon diagnosis of CPNB.

PMID- 24289891
TI  - Comfort from suicidal cognition in recurrently depressed patients.
AB  - BACKGROUND: Previous research has suggested that some individuals may obtain
      comfort from their suicidal cognitions. METHOD: This study explored clinical
      variables associated with comfort from suicidal cognition using a newly developed
      5 item measure in 217 patients with a history of recurrent depression and
      suicidality, of whom 98 were followed up to at least one relapse to depression
      and reported data on suicidal ideation during the follow-up phase. RESULTS:
      Results indicated that a minority of patients, around 15%, reported experiencing
      comfort from suicidal cognitions and that comfort was associated with several
      markers of a more severe clinical profile including both worst ever prior
      suicidal ideation and worst suicidal ideation over a 12 month follow-up period.
      LIMITATIONS: Few patients self-harmed during the follow-up period preventing an
      examination of associations between comfort and repetition of self-harm.
      CONCLUSIONS: These results, although preliminary, suggest that future theoretical
      and clinical research would benefit from further consideration of the concept of
      comfort from suicidal thinking.

PMID- 24289892
TI  - A randomized, double-blind, clinical trial comparing the efficacy and safety of
      Crocus sativus L. with fluoxetine for improving mild to moderate depression in
      post percutaneous coronary intervention patients.
AB  - OBJECTIVE: A significant correlation exists between coronary artery diseases and
      depression. The aim of this trial was to compare the efficacy and safety of
      saffron versus fluoxetine in improving depressive symptoms of patients who were
      suffering from depression after performing percutaneous coronary intervention
      (PCI). METHODS: In this randomized double-blind parallel-group study, 40 patients
      with a diagnosis of mild to moderate depression who had undergone PCI in the last
      six months were randomized to receive either fluoexetine (40mg/day) or saffron
      (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton
      depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were
      systemically recorded. RESULTS: By the study endpoint, no significant difference
      was detected between two groups in reduction of HDRS scores (P=0.62). Remission
      and response rates were not significantly different as well (P=1.00 and P=0.67;
      respectively). There was no significant difference between two groups in the
      frequency of adverse events during this trial. LIMITATIONS: Relatively small
      sample size and short observational period were the major limitations of this
      study. CONCLUSION: Short-term therapy with saffron capsules showed the same
      antidepressant efficacy compared with fluoxetine in patients with a prior history
      of PCI who were suffering from depression.

PMID- 24289893
TI  - Endometrial injury may increase the clinical pregnancy rate in normoresponders
      undergoing long agonist protocol ICSI cycles with single embryo transfer.
AB  - OBJECTIVE: To investigate the effect of endometrial injury on the clinical
      pregnancy rate in normoresponders undergoing long agonist protocol
      intracytoplasmic sperm injection (ICSI) cycles with single embryo transfer. STUDY
      DESIGN: Prospective case-control study. METHODS: One hundred and eighteen women
      (age <35 years, normoresponders with Grade I or II embryos for transfer) were
      included. Women in the intervention group (n=56) underwent endometrial biopsy on
      Day 3 of the menstrual cycle following downregulation. Women in the control group
      (n=62) did not undergo endometrial biopsy. RESULTS: The clinical and
      embryological characteristics were comparable in the two groups, and no
      significant difference was found in the fertilization rates (66.32% in the
      intervention group vs. 70.23% in the control group). The clinical pregnancy rate
      was 48.2% in the intervention group and 29.0% in the control group (p=0.025).
      Endometrial injury may increase the clinical pregnancy rate (odds ratio 2.27).
      The 'take home baby' rates were 33.9% and 17.7% in the intervention and control
      groups, respectively (p=0.035). CONCLUSION: Assisted reproductive technology
      treatment that is preceded by endometrial injury may increase the clinical
      pregnancy rate in women undergoing long agonist protocol ICSI cycles with single
      embryo transfer.

PMID- 24289894
TI  - Effects of olive mill wastewater physico-chemical treatments on polyphenol
      abatement and Italian ryegrass (Lolium multiflorum Lam.) germinability.
AB  - Direct spreading on agricultural lands may represent an environmentally friendly
      disposal method and a possible use of water and nutrients from olive mill
      wastewaters (OMWs). However, the agronomic use of OMWs is limited, among others
      by polyphenols, which exert phytotoxic effects. Activated charcoal (AC) has been
      recognized as a very effective agent for polyphenol abatement, as it enables an
      irreversible process of phenol adsorption. Addition of calcium hydroxide
      (Ca(OH)2) has also been described as a cheap and effective method in polyphenols
      abatement. However, the effects of Ca(OH)2 addition to OMW on seed germination
      are unclear. In this paper, the effects of AC and/or Ca(OH)2 on OMW polyphenols
      abatement, and Lolium multiflorum seed germination have been investigated. The
      highest polyphenols removal, approximately 95%, was observed when 80 g L(-1) of
      AC was added to OMWs (the maximum dose in this investigation). The addition of
      Ca(OH)2 not only improved the effectiveness of the AC treatment but also resulted
      in a significant rise in Lolium seed germination at the highest AC doses (60 and
      80 g L(-1)). Considering the high salinity (7300 MUS cm(-1)) of these
      wastewaters, low quantities of Ca(OH)2 may also exert a protective effect on soil
      structure counteracting the sodium-induced dispersion through the binding action
      of calcium cation on clays and organic matter. 

PMID- 24289895
TI  - Fractal dimension and mandibular cortical width in normal and osteoporotic men
      and women.
AB  - OBJECTIVE: To verify whether fractal dimensions (FD) on the mandibular trabecular
      and cortical bone and mandibular cortical width (MCW) differ between patients
      with normal bone mineral density (BMD) and osteoporosis. STUDY DESIGN: In this
      retrospective study, 133 dental panoramic radiographs from men aged >60 years and
      postmenopausal women with a bone densitometry report of the lumbar spine and hip
      classified as either normal or osteoporotic were selected. Fractal dimensions of
      five standardized trabecular and cortical mandibular regions of interest and
      mandibular cortical width were measured on the panoramic radiographs by an
      experienced oral radiologist, blinded to the densitometric diagnosis. The
      following statistical analyses were performed: ANOVA and a forward logistic
      stepwise regression to verify associations between dental panoramic measurements
      and the densitometric diagnosis. P values less than .05 indicated statistical
      significance. MAIN OUTCOME MEASURES: Fractal dimension and mandibular cortical
      width. RESULTS: Differences were found in the FD values on mandibular cortical
      bone and MCW between patients with normal BMD and with osteoporosis, but not in
      the FD values of trabecular bone. The odds of having lower mean values of MCW and
      FD on cortical bone were 2.16, 3125 and 1005 times in osteoporotic patients,
      respectively, compared with patients with normal BMD. CONCLUSION: The values of
      FD analysis on mandibular cortical bone and MCW were lower in women with
      osteoporosis. A well-adjusted logistic regression model showed that cortical bone
      measurements might be considered as auxiliary tools to referring patients for DXA
      exam.

PMID- 24289896
TI  - Predictive outcomes of revision total hip replacement--a consecutive series of
      1176 patients with a minimum 10-year follow-up.
AB  - The burden of revision total hip replacement (THR) surgery is increasing. With an
      increasing life expectancy and younger age of primary surgery this trend is set
      to continue. There are few data on the long-term outcome of revision THR. This
      retrospective study of 1176 consecutive revision THRs with a minimum 10-year
      follow-up from a University Teaching Hospital was undertaken to review implant
      survival and patient reported outcomes. Mean follow-up was 11 years with implant
      survival at 10 years of 82% (CI: 80-85). Implant survival varied between 58%
      (unexplained pain) to 84% (aseptic loosening) depending on the indication for
      revision surgery. Positive predictors of survival were age greater than 70 at the
      time of surgery (p=0.011), revision for aseptic loosening (p<0.01) and revision
      of both components or just the acetabular component (p<0.01). At the last review,
      mean Oxford Hip Score (OHS) was 34 (SD: 11.3) and 92% of the living patients with
      unrevised hips were satisfied with the outcome of revision surgery. This long
      term study has demonstrated that positive predictors of survival and outcome of
      revision THR surgery are age greater than 70 years, revision for aseptic
      loosening and component revision. This should aid surgeons in their counselling
      of patients prior to surgery. 

PMID- 24289897
TI  - Psychosocial interventions in perimenopausal and postmenopausal women: a
      systematic review of randomised and non-randomised trials and non-controlled
      studies.
AB  - Women's care during perimenopause and postmenopause is taking new paths to help
      women cope with both somatic manifestations and changes related to psychological
      and social factors. An updated, systematic review was conducted on non
      pharmacological psychosocial interventions with regard to peri- and
      postmenopause. Several databases complemented with reference lists and reviews
      were used to perform a literature search of any relevant article. Studies were
      selected if they included psychoeducational programmes, health education and
      promotion and cognitive-behavioural techniques applied to peri- or postmenopausal
      women, independently of study design, main outcomes and intervention comparators.
      A total of 33 reports and 3 relevant reviews published between 1987 and 2013 were
      included. Psychosocial options are promising intervention options for self
      management and self-care, as they provide multiple benefits with no side effects.
      Moreover, these options are recommended for women in clinical, subclinical and
      asymptomatic groups, as they offer women the agency and skills necessary to
      manage and relieve menopausal symptoms, as well as provide information and
      alternatives to prevent menopausal symptoms and to have a more positive
      experience during these life stages. These options do more than reduce distress
      and complaints, as they allow women in any condition to enjoy enhanced health,
      well-being and quality of life. Moreover, these options are accompanied by
      important cost reductions in pharmaceutical investment and healthcare.
      Nevertheless, several issues remain controversial or have scarcely been
      investigated, and additional high-quality research should address these issues
      properly in the future. Despite these limitations and the weaknesses of the
      review, the findings of this review are interesting and positive. Thus, we
      encourage women-focused institutions and policies (e.g., healthcare centres,
      public organisations and women's associations) to offer psychosocial
      interventions to peri- and postmenopausal women within a comprehensive healthcare
      paradigm. 

PMID- 24289898
TI  - Diagnostic value of parasternal pulmonary artery short-axis view for the
      anomalous origin of the left coronary artery from the pulmonary artery.
AB  - OBJECTIVE: To evaluate the diagnostic value of parasternal pulmonary artery (PA)
      short-axis view for the anomalous origin of left coronary artery (LCA) from the
      pulmonary artery by echocardiography. METHODS: A total of 13 patients (3 boys)
      aged from 2 months to 12 years were enrolled. Transthoracic echocardiography,
      including cross-sectional imaging and color Doppler flow imaging, were performed,
      and their diagnoses were confirmed by operation. RESULTS: Among the 13 patients,
      7 had LCA originated from the left posterior wall of PA, 2 from the posterior
      wall, and 4 from the right posterior wall. The PA short-axis view could visualize
      the anomalous origin of the LCA from left posterior or posterior wall of PA
      clearly. The LCA and aortic wall were overlapping at 3-4 o'clock at PA short-axis
      view in the patients with LCA originating from the right posterior wall of PA. It
      was similar with the image of the LCA originating from the aorta. But the blood
      flow was opposite to that of LCA with normal origin. CONCLUSIONS: The parasternal
      PA short-axis view is a good view to visualize the anomalous origin of the LCA.

PMID- 24289899
TI  - Coded excitation of ultrasonic guided waves in long bone fracture assessment.
AB  - Ultrasonic guided wave (GW) assessment of long bone fracture have conventionally
      been based on pulse excitation. However, the high attenuation during propagation
      diminishes the amplitude of received GWs and results in low signal-to-noise ratio
      (SNR). The Barker code (BC) excitation and the optimal binary code (OBC)
      excitation were utilized in this study to overcome this limitation. Both
      simulations and in vitro experiments were performed on the fractured cortical
      bone plate model, and measured signals from both the BC and OBC excitations were
      decoded using the finite impulse response least squares inverse filter (FIR-LSIF)
      and then compared with sine pulse (SP) excited signals. The results suggest the
      efficiency of coded excitation for amplitude and SNR improvement. Furthermore,
      time-frequency representation (TFR) analysis was applied to experimental signals;
      with increasing fracture depth, energy transformation between predominate GW
      modes A1 and S2 was confirmed. These results show the potential of using BC and
      OBC excitations to evaluate the depth of long bone fracture. 

PMID- 24289900
TI  - Bolt axial stress measurement based on a mode-converted ultrasound method using
      an electromagnetic acoustic transducer.
AB  - A method is proposed to measure the stress on a tightened bolt using an
      electromagnetic acoustic transducer (EMAT). A shear wave is generated by the
      EMAT, and a longitudinal wave is obtained from the reflection of the shear wave
      due to the mode conversion. The ray paths of the longitudinal and the shear wave
      are analyzed, and the relationship between the bolt axial stress and the ratio of
      time of flight between two mode waves is then formulated. Based on the above
      outcomes, an EMAT is developed to measure the bolt axial stress without loosening
      the bolt, which is required in the conventional EMAT test method. The
      experimental results from the measurement of the bolt tension show that the shear
      and the mode-converted longitudinal waves can be received successfully, and the
      ratio of the times of flight of the shear and the mode-converted longitudinal
      waves is linearly proportional to the bolt axial tension. The non-contact
      characteristic of EMAT eliminates the effect of the couplant and also makes the
      measurement more convenient than the measurement performed using the
      piezoelectric transducer. This method provides a promising way to measure the
      stress on tightened bolts. 

PMID- 24289901
TI  - Metastatic castration resistant prostate cancer: current strategies of management
      in the Middle East.
AB  - Although most patients with prostate cancer respond to initial androgen
      deprivation therapy, progression to castration-resistant prostate cancer (CRPC)
      is almost inevitable. In 2004, the docetaxel/prednisone regimen was approved for
      the management of patients with metastatic CRPC, becoming the standard first-line
      therapy. Recent advances have also led to an unprecedented number of approved new
      drugs; thus, providing several treatment options for patients with metastatic
      CRPC. Five new drugs have received US Food and Drug Administration-approval
      between 2010 and 2012: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a
      novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis
      inhibitor; enzalutamide, a novel androgen receptor inhibitor; and denosumab, a
      bone-targeting agent. Such drugs are either already marketed or about to be
      marketed in the Middle East. Data supporting the approval of each of these agents
      are described in this review, as are recent approaches to the treatment of
      metastatic CRPC. 

PMID- 24289902
TI  - Chemoradiation and brachytherapy in extrahepatic bile duct carcinoma.
AB  - BACKGROUND: To explore the role of radiotherapy in the extrahepatic bile duct
      carcinoma, and to understand if and when radiotherapy could be effective for this
      group of patients. METHODS: A systematic review of recently published literature
      was completed. Recent studies using radiotherapy with survival data, resection
      rates and quality of life data have been analyzed. RESULTS: There are no
      randomized trials regarding the treatment of extrahepatic cholangiocarcinoma. The
      bulk of available studies suggest that in some cases radio-chemotherapy can be
      used as adjuvant therapy. Radiotherapy could also have a role in unresectable
      cholangiocarcinoma: external radiotherapy or intraluminal brachytherapy--alone or
      in combination--could improve the outcome in selected patients. Finally,
      radiotherapy, and in particular intraluminal brachytherapy, could be used as a
      palliative treatment to improve the quality of life and in controlling symptoms.
      CONCLUSION: The role of radiotherapy in extrahepatic cholangiocarcinoma remains
      undefined due to the lack of randomized trials or otherwise properly controlled
      studies.

PMID- 24289903
TI  - Long-term growth and general health for the tiniest or most immature infants.
AB  - Given the improving survival rates of extremely preterm (EP, gestational age <28
      weeks) infants, there is a need to understand their general growth and health
      outcomes not only in childhood, but also into adulthood. EP children are shorter
      and lighter compared with term children at term-equivalent age; with time, the
      weight disadvantage diminishes but the height disadvantage remains relatively
      unchanged. EP children and young adults also have higher rates of reported health
      concerns, medical conditions and visual impairment. Hospital readmissions are
      higher in early childhood, mostly attributed to respiratory illness. Individuals
      born EP have reduced bone health and are at increased risk for metabolic
      disorders. Increased rates of conditions such as diabetes or pathological
      fractures are not reported in the literature, although follow-up studies so far
      have only tracked EP individuals into young adulthood. Consequently, health care
      utilization and costs are increased in EP children and young adults. A thorough
      knowledge of the health risks related to EP birth is essential in planning
      surveillance and intervention strategies to optimize their health and wellbeing.
      Despite the increased risk of health problems, EP young adults generally report
      their quality of life to be similar to that reported in their term counterparts. 

PMID- 24289904
TI  - Long-term outcome for the tiniest or most immature babies: survival rates.
AB  - This article focuses on the survival rates of the most immature babies considered
      viable from around the world. It discusses the various factors in terms of
      definition, inclusion criteria and policy which can result in marked differences
      in the apparent rates of delivery (all births), live birth, admission to neonatal
      intensive care and ultimately survival seen between otherwise similar countries,
      different regions of the same country, and even adjacent hospitals. Such
      variation in approach can result in major differences in reported survival and
      consequentially have large effects on apparent rates of adverse long-term
      outcome. 

PMID- 24289905
TI  - Functional outcomes of very premature infants into adulthood.
AB  - The outcomes of very low birth weight survivors born in the early post-neonatal
      intensive care era have now been reported to young adulthood in several
      longitudinal cohort studies, and more recently from large Scandinavian national
      databases. The latter reports corroborate the findings that despite disabilities,
      a significant majority of very low birth weight survivors are leading productive
      lives, and are functioning better than expected. This is reassuring, but there
      are still concerns about future psychopathology, cardiovascular and metabolic
      problems as they approach middle age. Although these findings may not be directly
      applicable to the current survivors of modern neonatal intensive care, they do
      provide a yardstick by which to project the outcomes of future survivors until
      more contemporaneous data are available. 

PMID- 24289906
TI  - The future of imaging biomarkers in radiologic practice: proceedings of the
      thirteenth annual ACR Forum.
AB  - The 2013 ACR Forum focused on the emerging field of imaging biomarkers and how
      best to integrate imaging biomarkers into clinical practice, promote research
      into imaging biomarkers, and leverage advances in bioinformatics. The
      recommendations generated from the Forum seek to inform ACR leadership on the
      best strategies to pursue to ensure that radiologists secure a preeminent role in
      the new era of precision and personalized medicine. 

PMID- 24289907
TI  - Abuse of methylphenidate in Germany: data from spontaneous reports of adverse
      drug reactions.
AB  - To retrieve insights into abuse/dependence of methylphenidate (MPH) in Germany, a
      query of a pharmacovigilance database was performed (observation interval: 1993
      until 2012). From 1190 reports of any ADR related to MPH, n=23 (2%) cases of MPH
      abuse were identified (mean age 29 years; male sex 78%; mean daily MPH-dosage 111
      +/- 126.6 mg). As oral application was predominant (70%), the majority of
      reported cases of MPH abuse might be due to pharmacologic neuroenhancement.

PMID- 24289908
TI  - Lack of association between brain-derived neurotrophic factor Val66Met
      polymorphism and aggressive behavior in schizophrenia.
AB  - We investigated the association of the Val66Met gene polymorphism in the Brain
      Derived Neurotrophic Factor (BDNF) gene with aggressive behavior among Southern
      Han Chinese schizophrenia patients. We used polymerase chain reaction-restriction
      fragment length polymorphism to determine the genotypes and the Modified Overt
      Aggression Scale (MOAS) to measure aggressive behavior. No significant
      differences in genotype or allele distribution of Val66Met were identified
      between aggressive and non-aggressive schizophrenia patients. 

PMID- 24289909
TI  - Haplotype analysis of the DISC1 Ser704Cys variant in Japanese suicide completers.
AB  - The present study investigated the genetic association of the disrupted-in
      schizophrenia 1 (DISC1) gene with suicide using 398 Japanese completed suicides
      and 511 healthy controls. The functional Ser704Cys variant of DISC1 was nominally
      associated with completed suicide. Enhanced evidence of association was observed
      in a multi-marker sliding window haplotype analysis (the lowest p=0.002). These
      findings warrant further studies with a larger sample size to confirm the
      association of DISC1 with suicide. 

PMID- 24289910
TI  - Improving repeatability of setting volume origin and coordinate system for 3D
      gait analysis.
AB  - This study investigated the variability arising from replacement of different
      calibration objects. A new calibration object (L-Frame) was instigated which
      consisted of four markers screwed into fixed positions in the floor, to ensure
      consistency between replacements. The variability of a healthy subject's joint
      moments from replacement of different calibration objects (5 marker wand and L
      Frame) was compared to the subject's stride-to-stride repeatability (SSR).
      Overall the L-Frame calibration object demonstrated the least amount of variation
      during object replacement for both sagittal and coronal joint moments. In
      particular for the coronal ankle moment the 5 marker wand positioned at the end
      of the force-plate alignment had a variability of 81% of SSR, while the L-Frame
      showed only 3% of SSR. Utilising the L-Frame to set the volume origin and global
      coordinate system achieved the most consistent results, which is important for
      assuring reliable measurements during 3-Dimensional Gait Analysis (3DGA). 

PMID- 24289911
TI  - Fluorescence-enhanced robotic radical prostatectomy using real-time
      lymphangiography and tissue marking with percutaneous injection of unconjugated
      indocyanine green: the initial clinical experience in 50 patients.
AB  - BACKGROUND: Pilot studies have demonstrated the utility of indocyanine green
      (ICG) sentinel lymphadenectomy for prostate cancer. Prior work has used ICG with
      radiocontrast agents injected at a separate procedure and relied on assistant
      controlled fluorescence systems, making the technique costly and cumbersome.
      OBJECTIVE: To describe the initial optimization and feasibility of fluorescence
      enhanced robotic radical prostatectomy (FERRP) using real-time injection of ICG
      for tissue marking and identification of sentinel lymphatic drainage visualized
      by a fully integrated surgeon-controlled system. DESIGN, SETTING, AND
      PARTICIPANTS: Patients with clinically localized prostate cancer at a tertiary
      referral center were offered FERRP. Ten patients participated in a pilot arm in
      which ICG dosing and injection technique were optimized. Fifty consecutive
      patients then underwent FERRP. SURGICAL PROCEDURE: After development of the space
      of Retzius, 0.4 ml of a 2.5 mg/ml ICG solution were injected into each lobe of
      the prostate using a robotically guided percutaneous needle. After ICG was
      allowed to travel through the pelvic lymphatics, lymphadenectomy was performed
      from the endopelvic fascia to the aortic bifurcation. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Parameters describing the time course of tissue
      fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic
      packets containing fluorescent nodes were considered sentinel. RESULTS AND
      LIMITATIONS: Percutaneous, robotic-guided ICG injection proved superior to
      cystoscope or transrectal delivery. Tissue marking was achieved in all patients,
      positively identifying the prostate with uniform fluorescence relative to the
      obturator nerve, seminal vesicles, vas deferens, and neurovascular pedicles at a
      mean time of 10 min postinjection. Sentinel nodes were identified in 76% of
      patients at a mean time of 30 min postinjection and had 100% sensitivity, 75.4%
      specificity, 14.6% positive predictive value, and 100% negative predictive value
      for the detection of nodal metastasis. CONCLUSIONS: FERRP is safe, feasible, and
      allows for reliable prostate tissue marking and identification of sentinel
      lymphatic drainage in the majority of patients. ICG sentinel nodes are highly
      sensitive but relatively nonspecific for the detection of nodal metastasis.

PMID- 24289912
TI  - Distribution and risk factors of Trichomonas vaginalis infection in England: an
      epidemiological study using electronic health records from sexually transmitted
      infection clinics, 2009-2011.
AB  - We used data from the Genitourinary Medicine Clinic Activity Dataset (GUMCAD)
      over a 3-year period (2009-2011) to investigate the distribution and risk factors
      of Trichomonas vaginalis infection in England. Socio-demographic and clinical
      risk factors associated with a diagnosis of T. vaginalis were explored using
      multivariable logistic regression. Rates of T. vaginalis infection were highest
      in London and the West Midlands. For men and women, T. vaginalis infection was
      significantly associated with: older age compared to those aged 20-24 years, non
      white ethnicity (in particular black Caribbean and black 'other' ethnic groups),
      and birth in the Caribbean vs. birth in the UK. Current gonorrhoea or chlamydia
      infection was associated with a diagnosis of T. vaginalis in women. Further
      research is required to assess the public health impact and cost-effectiveness of
      introducing targeted screening for women at high risk of infection in areas of
      higher prevalence.

PMID- 24289913
TI  - Validation and calibration of the activPALTM for estimating METs and physical
      activity in 4-6 year olds.
AB  - OBJECTIVES: Examine the predictive validity of the activPALTM metabolic
      equivalents equation, develop an activPALTM threshold value to define moderate-to
      vigorous-intensity physical activities, and examine the classification accuracy
      of the developed moderate-to vigorous-intensity physical activities threshold
      value in 4- to 6-year-old children. DESIGN: A sample of forty 4- to 6-year-old
      children from the Illawarra region in New South Wales, Australia were included in
      data analysis. METHODS: Participants completed a ~ 150-min room calorimeter
      protocol involving age-appropriate sedentary behaviors, light-intensity physical
      activities and moderate-to vigorous-intensity physical activities. activPALTM
      accelerometer counts were collected over 15s epochs. Energy expenditure measured
      by room calorimetry and direct observation were used as the criterion measure.
      Predicted metabolic equivalents were calculated using the activPALTM metabolic
      equivalents equation (activPALTM software version 5.8.0). Predictive validity was
      evaluated using dependent-samples t-tests. Participants were randomly allocated
      into two groups to develop and cross-validate an intensity threshold for moderate
      to vigorous-intensity physical activities. Receiver operating characteristic
      curve analysis was used to determine moderate-to vigorous-intensity physical
      activities threshold. The classification accuracy of the developed threshold was
      cross-validated using sensitivity, specificity, and area under the receiver
      operating characteristic-curve. RESULTS: The activPALTM metabolic equivalents
      equation significantly overestimated metabolic equivalents during sedentary
      behaviors and significantly underestimated metabolic equivalents for light
      intensity physical activities, moderate-to vigorous-intensity physical activities
      and total metabolic equivalents compared to measured metabolic equivalents (all
      P<0.001). The developed threshold of >=1418 counts per 15s resulted in good
      classification accuracy for moderate-to vigorous-intensity physical activities.
      CONCLUSION: The current activPALTM metabolic equivalents equation requires
      further development before it can be used to accurately estimate metabolic
      equivalents in preschoolers. The developed threshold exhibited acceptable
      classification accuracy for moderate-to vigorous-intensity physical activities;
      however studies cross-validating this moderate-to vigorous-intensity physical
      activities threshold in free-living preschool-aged children are recommended.

PMID- 24289914
TI  - Cataract surgery in patients with Fuchs' endothelial corneal dystrophy: when to
      consider a triple procedure.
AB  - PURPOSE: To ascertain preoperative and intraoperative factors that predict the
      need for endothelial keratoplasty (EK) in patients with Fuchs' endothelial
      corneal dystrophy (FECD) undergoing cataract surgery. DESIGN: Prospective,
      observational cohort study. PARTICIPANTS: Eighty-nine patients (89 eyes) with
      FECD who require cataract surgery. METHODS: One month before cataract surgery, we
      assessed best-corrected visual acuity, contrast sensitivity, straylight,
      keratometry, ultrasonic pachymetry, intraocular pressure, 7 corneal features of
      FECD and cataract density at slit-lamp examination, and corneal backscatter using
      in vivo confocal microscopy (IVCM; Confoscan 4, NIDEK Technologies, Padova,
      Italy). After surgery, measurements were repeated at 1, 2, and 12 months. We used
      stepwise binary logistic regression analysis to evaluate 30 preoperative and 5
      intraoperative parameters for their ability to predict the postoperative need for
      EK. Receiver operating characteristic (ROC) curves of the predictive factors were
      used to identify their optimal cutoff points. MAIN OUTCOME MEASURES: Central
      corneal thickness (CCT) and backscatter at the basal epithelial cell layer (EV).
      RESULTS: After cataract surgery, 35 (39%) of 89 eyes underwent EK to restore
      vision. Of all preoperative and intraoperative parameters, only CCT and EV were
      identified as significant factors, predictive of the need for EK. The area under
      the ROC curve of EV was significantly higher than that of CCT (P = 0.003),
      whereas a combination of both factors in a linear discriminant function did not
      improve the predictive value (P = 0.66). As optimal cutoff points, we chose 1894
      scatter units for EV and 630 MUm for CCT. Both cutoff points correspond with a
      specificity of 94% and represent sensitivity of 63% for EV and 40% for CCT.
      CONCLUSIONS: Backscatter at the basal epithelial cell layer measured by IVCM
      predicts the need for EK after cataract surgery in patients with FECD. As an
      indicator for the corneal hydration state, the EV improves patient selection for
      combined cataract surgery and EK. In deciding whether to perform a triple
      procedure, CCT remains a less effective, but adequate, alternative. Regardless of
      the predictive factor used, a tailor-made approach is recommended accounting for
      individuals' expectations.

PMID- 24289915
TI  - Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of
      the OPUS-1 phase 3 study.
AB  - PURPOSE: To assess the efficacy and safety of lifitegrast ophthalmic solution
      5.0% compared with placebo in subjects with dry eye disease. DESIGN: Prospective,
      randomized, double-masked, placebo-controlled, parallel arm, multicenter clinical
      trial. PARTICIPANTS: A total of 588 adult subjects with dry eye disease. METHODS:
      Eligible subjects were randomized 1:1 to receive topically administered
      lifitegrast (5.0%) or placebo (vehicle) twice daily for 84 days after a 14-day
      open-label placebo run-in period. After enrollment (day 0), subjects were
      evaluated at days 14, 42, and 84. Key objective (fluorescein and lissamine
      staining scores [Ora scales]) and subjective (Ocular Surface Disease Index
      [OSDI], 7-item visual analog scale, and ocular discomfort score [Ora scale])
      measures were assessed at all visits. MAIN OUTCOME MEASURES: The primary
      objective efficacy measure (sign) was mean change from baseline inferior corneal
      staining score (ICSS) at day 84. The co-primary subjective efficacy measure
      (symptom) was the mean change from baseline in the visual-related function
      subscale score of the Ocular Surface Disease Index (VR-OSDI). Supportive measures
      included corneal fluorescein scores (superior, central, total region) and
      conjunctival lissamine scores (nasal, temporal, total region) and symptom scores
      at day 84. RESULTS: The study met the primary objective efficacy ICSS end point
      in demonstrating superiority of lifitegrast compared with placebo (P = 0.0007).
      Lifitegrast significantly reduced corneal fluorescein staining (superior, P =
      0.0392; total cornea, P = 0.0148) and conjunctival lissamine staining (nasal, P =
      0.0039; total conjunctiva, P = 0.0086) at day 84 versus placebo. Significant (P <
      0.05) improvements in nasal and total lissamine scores were observed at day 14
      and maintained through day 84. The study did not meet the co-primary subjective
      VR-OSDI measure (P = 0.7894). However, significant improvements were observed at
      day 84 in ocular discomfort (P = 0.0273) and eye dryness (P = 0.0291), the most
      common and severe symptoms reported at baseline in both groups. There were no
      unanticipated or serious ocular adverse events (AEs). The most frequent reported
      ocular AEs were transient intermittent instillation site symptoms (irritation,
      discomfort) primarily on the initial lifitegrast dose at day 0. CONCLUSIONS:
      Lifitegrast ophthalmic solution 5.0% significantly reduced corneal fluorescein
      and conjunctival lissamine staining and improved symptoms of ocular discomfort
      and eye dryness compared with placebo when administered twice daily over 84 days.

PMID- 24289916
TI  - Discriminant value of custom ocular response analyzer waveform derivatives in
      keratoconus.
AB  - PURPOSE: To evaluate the performance of corneal hysteresis (CH), corneal
      resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA)
      variables in distinguishing keratoconus (KC) from the nondiseased state. DESIGN:
      Retrospective case series. PARTICIPANTS: Fifty-four eyes of 27 unaffected
      patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de
      Janeiro, Brazil. METHODS: Sixteen candidate variables were derived from exported
      ORA signals to characterize putative indicators of biomechanical behavior. Area
      under the receiver operating characteristic curve (AUC) and the Z statistic were
      used to compare diagnostic performance. MAIN OUTCOME MEASURES: Discriminant value
      of standard and derived ORA variables as measured by AUC. RESULTS: Fifteen of 16
      candidate variables performed significantly better than chance (AUC, >0.5) at
      discriminating KC. Diagnostic performance was greatest for a custom variable
      related to the depth of deformation as defined by the minimum applanation signal
      intensity during corneal deformation (concavity(min); mean AUC +/- standard
      error, 0.985 +/- 0.002) and a new measure incorporating the pressure-deformation
      relationship of the entire response cycle (hysteresis loop area, 0.967 +/-
      0.002). Z statistics assessing the discriminative value of each of the top 5
      variables demonstrated superiority to CH (AUC, 0.862 +/- 0.002). Concavity(min)
      had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity,
      91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated
      the most consistent relationships to KC severity. CONCLUSIONS: Investigator
      derived ORA variables related to the depth of deformation and the pressure
      deformation relationship demonstrated very high test accuracy for detecting the
      presence of KC. Beyond their diagnostic value, the candidate variables described
      in this report provide mechanistic insight into the nature of the ORA signal and
      the characteristic changes in corneal dynamics associated with KC.

PMID- 24289917
TI  - Predicting progression of glaucoma from rates of frequency doubling technology
      perimetry change.
AB  - PURPOSE: To evaluate the ability of longitudinal frequency doubling technology
      (FDT) to predict the development of glaucomatous visual field loss on standard
      automated perimetry (SAP) in glaucoma suspects. DESIGN: Prospective,
      observational cohort study. PARTICIPANTS: The study included 587 eyes of 367
      patients with suspected glaucoma at baseline selected from the Diagnostic
      Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma
      Evaluation Study (ADAGES). These eyes had an average of 6.7 +/- 1.9 FDT tests
      during a mean follow-up time of 73.1 +/- 28.0 months. METHODS: Glaucoma suspects
      had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of
      glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline.
      Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed
      within 6 months of SAP testing. The study end point was the development of 3
      consecutive abnormal SAP test results. Joint longitudinal survival models were
      used to evaluate the ability of rates of FDT pattern standard deviation (PSD)
      change to predict the development of visual field loss on SAP, adjusting for
      confounding variables (baseline age, mean IOP, corneal thickness, and follow-up
      measurements of SAP PSD). MAIN OUTCOME MEASURES: The R(2) index was used to
      evaluate and compare the predictive abilities of the model containing
      longitudinal FDT PSD data with the model containing only baseline data. RESULTS:
      Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up.
      The mean rate of FDT PSD change in eyes that developed SAP visual field loss was
      0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT
      PSD and slopes of FDT PSD change were significantly predictive of progression,
      with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04
      1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04),
      respectively. The longitudinal model performed significantly better than the
      baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24),
      respectively. CONCLUSIONS: Rates of FDT PSD change were highly predictive of the
      development of SAP visual field loss in glaucoma suspects. This finding suggests
      that longitudinal FDT evaluation may be useful for risk stratification of
      patients with suspected glaucoma.

PMID- 24289919
TI  - Achieving target refraction after cataract surgery.
AB  - PURPOSE: To evaluate the difference between target and actual refraction after
      phacoemulsification and intraocular lens implantation at an academic teaching
      institution's Comprehensive Ophthalmology Service. DESIGN: Retrospective study.
      PARTICIPANTS: We examined 1275 eye surgeries for this study. METHODS: All
      consecutive cataract surgeries were included if they were performed by an
      attending or resident surgeon from January through December 2010. Postoperative
      refractions were compared with preoperative target refractions. Patients were
      excluded if they did not have a preoperative target refraction documented or if
      they did not have a recorded postoperative manifest refraction within 90 days.
      MAIN OUTCOME MEASURES: The main outcome measure was percentage of cases achieving
      a postoperative spherical equivalent +/- 1.0 diopter (D) of target spherical
      equivalent. RESULTS: We performed 1368 cataract surgeries from January through
      December of 2010. Of these, 1275 (93%) had sufficient information for analysis.
      Of the included cases, 94% (1196 of 1275) achieved +/- 1.0 D of target refraction
      by 90 days after cataract surgery. CONCLUSIONS: This paper establishes a new
      benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of
      target refraction after cataract surgery. The refractive outcomes after cataract
      surgery at this academic teaching institution were higher than average
      international benchmarks.

PMID- 24289918
TI  - En face enhanced-depth swept-source optical coherence tomography features of
      chronic central serous chorioretinopathy.
AB  - OBJECTIVE: To characterize en face features of the retinal pigment epithelium
      (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR)
      using a high-speed, enhanced-depth swept-source optical coherence tomography (SS
      OCT) prototype. DESIGN: Consecutive patients with chronic CSCR were prospectively
      examined with SS-OCT. PARTICIPANTS: Fifteen eyes of 13 patients. METHODS: Three
      dimensional 6*6 mm macular cube raster scans were obtained with SS-OCT operating
      at 1050 nm wavelength and 100000 A-lines/sec with 6 MUm axial resolution.
      Segmentation of the RPE generated a reference surface; en face SS-OCT images of
      the RPE and choroid were extracted at varying depths every 3.5 MUm (1 pixel).
      Abnormal features were characterized by systematic analysis of multimodal fundus
      imaging, including color photographs, fundus autofluorescence, fluorescein
      angiography, and indocyanine-green angiography (ICGA). MAIN OUTCOME MEASURES: En
      face SS-OCT morphology of the RPE and individual choroidal layers. RESULTS: En
      face SS-OCT imaging at the RPE level revealed absence of signal corresponding to
      RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the
      choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At
      the level of Sattler's layer, en face SS-OCT documented focal choroidal dilation
      in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At
      the level of Haller's layer, these same features were observed in 3 of 15 eyes
      (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these
      choroidal vascular abnormalities were seen just below areas of RPE abnormalities.
      In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS
      OCT features corresponded to the neovascular lesions. CONCLUSIONS: High-speed,
      enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of
      pathologic features of the RPE and choroid in eyes with chronic CSCR not usually
      appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems
      to be a useful tool in the identification of CNV without the use of angiography.
      This in vivo documentation of the RPE and choroidal vasculature at variable
      depths may help elucidate the pathophysiology of disease and can contribute to
      the diagnosis and management of chronic CSCR.

PMID- 24289921
TI  - Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and
      enhancer fidelity.
AB  - H3K27me3 is deposited at promoters by the preferential association of Polycomb
      repressive complex 2 (PRC2) with CpG-rich DNA elements regulating development by
      repressing gene transcription. H3K27 is also present in mono- and dimethylated
      states; however, the functional roles of H3K27me1 and H3K27me2 deposition remain
      poorly characterized. Here, we show that PRC2 activity is not only associated
      with H3K27me3 but also regulates all forms of H3K27 methylation in a spatially
      defined manner, contributing to different genomic functions in mouse embryonic
      stem cells. H3K27me1 accumulates within transcribed genes, promotes
      transcription, and is regulated by Setd2-dependent H3K36me3 deposition.
      Contrarily, H3K27me2 is present on approximately 70% of total histone H3 and is
      distributed in large chromatin domains, exerting protective functions by
      preventing firing of non-cell-type-specific enhancers. Considering that only 5%
      10% of deregulated genes in PRC2-deficient cells are direct H3K27me3 targets, our
      data support an active role for all H3K27 methylated forms in regulating
      transcription and determining cell identity.

PMID- 24289920
TI  - Systemic complement inhibition with eculizumab for geographic atrophy in age
      related macular degeneration: the COMPLETE study.
AB  - PURPOSE: To evaluate the effect of eculizumab, a systemic inhibitor of complement
      component (C5), on the growth of geographic atrophy (GA) in patients with age
      related macular degeneration (AMD). DESIGN: Prospective, double-masked,
      randomized clinical trial. PARTICIPANTS: Patients with GA measuring from 1.25 to
      18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS:
      Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6
      months. In the eculizumab treatment arm, the first 10 patients received a low
      dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until
      week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly
      for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group
      was infused with saline. Patients were observed off treatment for an additional
      26 weeks. Both normal-luminance and low-luminance visual acuities were measured
      throughout the study, and the low-luminance deficits were calculated as the
      difference between the letter scores. MAIN OUTCOME MEASURES: Change in area of GA
      at 26 weeks. RESULTS: Thirty eyes of 30 patients were enrolled. Eighteen fellow
      eyes also met inclusion criteria and were analyzed as a secondary endpoint. For
      the 30 study eyes, mean square root of GA area measurements +/- standard
      deviation at baseline were 2.55 +/- 0.94 and 2.02 +/- 0.74 mm in the eculizumab
      and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean
      of 0.19 +/- 0.12 and 0.18 +/- 0.15 mm in the eculizumab and placebo groups,
      respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37
      +/- 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 +/- 0.21 mm in
      the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet
      AMD. No drug-related adverse events were identified. CONCLUSIONS: Systemic
      complement inhibition with eculizumab was well tolerated through 6 months but did
      not decrease the growth rate of GA significantly. However, there was a
      statistically significant correlation between the low-luminance deficit at
      baseline and the progression of GA over 6 months.

PMID- 24289923
TI  - The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation.
AB  - The breast and ovarian cancer-specific tumor suppressor BRCA1, along with its
      heterodimer partner BRCA1-associated RING domain protein (BARD1), plays important
      roles in DNA repair, centrosome regulation, and transcription. To explore further
      functions of BRCA1/BARD1, we performed mass spectrometry analysis and identified
      Obg-like ATPase 1 (OLA1) as a protein that interacts with the carboxy-terminal
      region of BARD1. OLA1 directly bound to the amino-terminal region of BRCA1 and
      gamma-tubulin. OLA1 localized to centrosomes in interphase and to the spindle
      pole in mitotic phase, and its knockdown resulted in centrosome amplification and
      the activation of microtubule aster formation. OLA1 with a mutation observed in
      breast cancer cell line, E168Q, failed to bind BRCA1 and rescue the OLA1
      knockdown-induced centrosome amplification. BRCA1 variant I42V also abrogated the
      binding of BRCA1 to OLA1. These findings suggest that OLA1 plays an important
      role in centrosome regulation together with BRCA1. 

PMID- 24289922
TI  - The DNA replication program is altered at the FMR1 locus in fragile X embryonic
      stem cells.
AB  - Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene
      that appears to occur during oogenesis and during early embryogenesis. One model
      proposes that repeat instability depends on the replication fork direction
      through the repeats such that (CNG)n hairpin-like structures form, causing DNA
      polymerase to stall and slip. Examining DNA replication fork progression on
      single DNA molecules at the endogenous FMR1 locus revealed that replication forks
      stall at CGG repeats in human cells. Furthermore, replication profiles of FXS
      human embryonic stem cells (hESCs) compared to nonaffected hESCs showed that fork
      direction through the repeats is altered at the FMR1 locus in FXS hESCs, such
      that predominantly the CCG strand serves as the lagging-strand template. This is
      due to the absence of replication initiation that would typically occur upstream
      of FMR1, suggesting that altered replication origin usage combined with fork
      stalling promotes repeat instability during early embryonic development. 

PMID- 24289931
TI  - Targeted Behavioral Therapy for childhood generalized anxiety disorder: a time
      series analysis of changes in anxiety and sleep.
AB  - This study examined the efficacy of Targeted Behavioral Therapy (TBT), a newly
      developed intervention targeting features of childhood generalized anxiety
      disorder (GAD). Using a time-series design, 4 children (7-12 years) with primary
      GAD were treated with TBT, which includes sleep improvement strategies,
      systematic desensitization for reducing intolerance of uncertainty, and in vivo
      exposures for anxiety. Diagnostic interviews and questionnaires were administered
      at baseline, post-treatment and 3 months follow-up. Anxiety symptoms and sleep
      characteristics/problems were rated weekly during a 4-week baseline and 14-weeks
      of treatment. Two children remitted at post-treatment and no child had a GAD
      diagnosis at follow-up. Child but not parent report revealed improvements in both
      worry and sleep. Despite improvements from pre- to post-assessment, considerable
      symptom fluctuation observed during the baseline period preclude conclusion that
      symptom changes are specifically attributable to the course of treatment.
      Overall, preliminary support is provided for the efficacy of TBT for childhood
      GAD. 

PMID- 24289924
TI  - Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA
      damage response.
AB  - While p53 activation has long been studied, the mechanisms by which its targets
      genes are restored to their preactivation state are less clear. We report here
      that TAF1 phosphorylates p53 at Thr55, leading to dissociation of p53 from the
      p21 promoter and inactivation of transcription late in the DNA damage response.
      We further show that cellular ATP level might act as a molecular switch for Thr55
      phosphorylation on the p21 promoter, indicating that TAF1 is a cellular ATP
      sensor. Upon DNA damage, cells undergo PARP-1-dependent ATP depletion, which is
      correlated with reduced TAF1 kinase activity and Thr55 phosphorylation, resulting
      in p21 activation. As cellular ATP levels recover, TAF1 is able to phosphorylate
      p53 on Thr55, which leads to dissociation of p53 from the p21 promoter. ChIP
      sequencing analysis reveals p53 dissociates from promoters genome wide as cells
      recover from DNA damage, suggesting the general nature of this mechanism.

PMID- 24289932
TI  - Remediation of 1,2,3-trichlorobenzene contaminated soil using a combined thermal
      desorption-molten salt oxidation reactor system.
AB  - A combined thermal desorption (TD)-molten salt oxidation (MSO) reactor system was
      applied to remediate the 1,2,3-trichlorobenzene (1,2,3-TCB) contaminated soil.
      The TD reactor was used to enrich the contaminant from soil, and its
      dechlorination of the contaminant was achieved in the MSO reactor. The optimum
      operating conditions of TD, and the effects of MSO reactor temperatures, additive
      amounts of the TCB on destruction and removal efficiency (DRE) of TCB and
      chlorine retention efficiency (CRE) were investigated. The reaction mechanism and
      pathway were proposed as well. The combined system could remediate the
      contaminated soil at a large scale of concentration from 5 to 25gkg(-1), and the
      DRE and CRE reached more than 99% and 95%, respectively, at temperatures above
      850 degrees C. The reaction emissions included C6H6, CH4, CO and CO2, and
      chlorinated species were not detected. It was found that a little increase in the
      temperature can considerably reduce the emission of C6H6, CH4, and CO, while the
      CO2 level increased. 

PMID- 24289933
TI  - Occupational exposure to solid chemical agents in biomass-fired power plants and
      associated health effects.
AB  - Occupational exposure to aluminium, arsenic, lead, cadmium, and manganese can
      increase the risk of numerous neurophysiological changes in workers, and may lead
      to conditions resembling Parkinson's and Alzheimer's disease. However, although
      the health hazard aspect of these agents has been examined, biomass-fired power
      plant workers' exposure to them remains a neglected issue. The purpose of this
      study was to measure maintenance and ash removal workers' multiple exposures to
      inhalable dust, metals, and crystalline silica during their work tasks in biomass
      fired power plants. Maintenance and ash removal workers were exposed to high
      inhalable dust concentrations inside biomass-fired boilers. The median air
      inhalable dust concentration in workers' breathing zones were 33 mg m(-3) and 120
      mg m(-3) in ash removal and maintenance tasks, respectively. The median
      concentration of manganese (0.31 mg m(-3)) exceeded the occupational exposure
      limit in worker's breathing zone samples in maintenance tasks. The most evident
      exposure-associated health risk from multiple exposures to metals was that of
      cancer, followed by central nervous system disorders, lower respiratory tract
      irritation, and finally upper respiratory tract irritation. To avoid the above
      mentioned health effects, powered air respirators with ABEK+P3 cartridges and
      carbon monoxide gas detectors are recommended as the minimum requirement for
      these work tasks. A compressed air breathing apparatus is the best form of
      protection for the most demanding work phases inside boilers in biomass-fired
      power plants.

PMID- 24289934
TI  - Comments on the scoring guideline of the personal and social performance scale
      (PSP).

PMID- 24289935
TI  - Towards a sociology of health and healthcare.

PMID- 24289936
TI  - The pandemic subject: Canadian pandemic plans and communicating with the public
      about an influenza pandemic.
AB  - In this paper, I examine the goals for pandemic public communication as outlined
      in two Canadian plans for pandemic planning and infection control. I critique
      these strategies by drawing on Foucault's notions of governmentality and
      biopower. My argument is that the public health communication campaign goals
      reviewed rest upon a particular conceptualization of health in the context of
      pandemic planning as an individual/family duty, and that scientific/medical
      expert knowledge is most appropriate for guiding pandemic planning. This study
      contributes to a sociological understanding of how pandemic preparedness and
      infection control are represented in Canadian pandemic plans, how public health
      shapes pandemic communication messages in Canada, and the implications of those
      messages for subjectivity and notions of citizenship. 

PMID- 24289937
TI  - [Territorial translation of the National Health and Nutrition Program in Midi
      Pyrenees, France].
AB  - Inspired by the Hygienist Movement, which associates good health with regular,
      moderate exercise, the National Health and Nutrition Program identifies a lack of
      physical activity as a risk factor for many chronic diseases. As such, the
      Program encourages people to take care of their bodies by inciting a moral
      obligation to develop a physically active lifestyle and follow a healthy diet.
      With the overall goal of improving the health of the population by acting on
      nutrition, the Program focuses on primary prevention, screening and early
      treatment of conditions like heart disease, cancer, obesity, osteoporosis and
      diabetes. As an incentive program developed in keeping with the biopolitical
      views of the 1970s that saw education as an alternative means to hospitals for
      achieving good health, the Program is also a good public action tool for
      controlling costs. 

PMID- 24289938
TI  - [Linguistic minorities in Canada and health].
AB  - Official language minorities (Francophones outside of Quebec and Anglophones in
      Quebec) make up about 6.4% of the Canadian population. Even though the Canadian
      constitution gives legal equality status to French and English, there is still
      room to ask if this equality is maintained in the health sector. In other words,
      do Francophone and Anglophone communities of Canada have the same health profiles
      regardless of their minority or majority status? Do they have access to the same
      health services and in the same conditions? The objective of this paper is to
      identify the health issues associated with belonging to a linguistic minority.
      Our research allows us to highlight the social and health disparities that can be
      attributed to belonging to a minority. In the Canadian context, which has two
      official languages, an equitable health policy will have to take into
      consideration language as a determinant of health. 

PMID- 24289939
TI  - Beyond 'run, knit and relax': can health promotion in Canada advance the social
      determinants of health agenda?
AB  - Can health promotion in Canada effectively respond to the challenge of reducing
      health inequities presented by the WHO Commission on Social Determinants of
      Health? Against a background of failure to take seriously issues of social
      structure, I focus in particular on treatments of stress and its effects on
      health, and on the destructive congruence of Canadian health promotion
      initiatives with the neoliberal "individualization" of responsibility for (ill)
      health. I suggest that the necessary reinvention of the health promotion
      enterprise is possible, but implausible. 

PMID- 24289940
TI  - [Adaptability of physicians offering primary care to the poor: social competency
      revisited].
AB  - This paper attempts to go deeper into the topic of social competency of
      physicians who provide primary care to populations living in poverty in Montreal.
      Adaptability as well as the ability to tailor practices according to patient
      expectations, needs and capabilities were found to be important in the
      development of the concept of social competency. The case of paternalism is used
      to demonstrate how a historically and socially contested medical approach is
      readapted by players in certain contexts in order to better meet patient
      expectations. This paper presents data collected in a qualitative study
      comprising 25 semi-supervised interviews with physicians recognized by their
      peers as having developed exemplary practices in Montreal's impoverished
      neighbourhoods. 

PMID- 24289941
TI  - Standards and stories: the interactional work of informed choice in Ontario
      midwifery care.
AB  - This paper uses a discourse-rhetorical approach to analyze how Ontario midwives
      and their clients interactionally accomplish the healthcare communicative process
      of "informed choice." Working with four excerpts from recorded visits between
      Ontario midwives and women, the analysis focuses on the discursive rendering
      during informed choice conversations of two contrasting kinds of evidence -
      professional standards and story-telling - related to potential interventions
      during labour. We draw on the concepts of discursive hybridity (Sarangi and
      Roberts 1999) and recontextualization (Linell 1998; Sarangi 1998) to trace the
      complex and creative ways in which the conversational participants reconstruct
      the meanings of these evidentiary sources to address their particular care
      contexts. This analysis shows how, though very different in their forms, both
      modes of evidence function as hybrid and flexible discursive resources that
      perform both instrumental and social-relational healthcare work.

PMID- 24289942
TI  - Home healthcare and family responsibility: a critical discourse analysis of talk
      and text.
AB  - This paper addresses how families' roles and responsibility for care are
      constructed within home health (in contrast to the responsibility of home
      health). A discourse analysis informed by a critical theoretical approach was
      used to analyze qualitative interviews with 13 home health managers and clinical
      leaders in British Columbia, alongside home care documents. When referring to
      family involvement, there was an emphasis on the importance of supporting a
      client's choice to stay at home. Government and agency documents describe family
      members as primary providers, with home health having a supplementary role.
      Agencies seek to avoid "substituting" for family care. Family responsibility is
      characterized as having both moral and structural value. Nonetheless, some
      participants advocated flexibility and recognized potential caregiving
      challenges. Data provide examples of how agency expectations are communicated to
      clients and families and become embedded within practice and policy. Findings are
      viewed within the broader organizational context as representing the
      "responsibilization" of support. 

PMID- 24289943
TI  - Lifestyle as a health risk for family caregivers with least life satisfaction, in
      home-based post-stroke caring.
AB  - Our purpose was to clarify that caregiving roles represent a situation of risk
      for the health of family caregivers, in home-based caring two years after
      cerebrovascular disease. Our aim was to determine the social and emotional
      repercussions of the event on family caregivers. Family caregivers living at home
      with stroke survivors were identified by a national survey. The Life Satisfaction
      (LS) national indicator for Luxembourg is 7.9/10, while in Canada it stands at
      7.7. Caregivers with a LS level <= 7 were more likely to care for survivors
      affected by motor, sensory and memory neurological impairments. For a great
      majority, these impairments led to serious upheaval among families, and for
      spouses it was "a drama." For family caregivers with a least life satisfaction,
      their lifestyle poses a real health risk for the public health system. 

PMID- 24289944
TI  - Sharing bodies: the impact of the biomedical model of pregnancy on women's
      embodied experiences of the transition to motherhood.
AB  - This paper explores how a medicalized view of pregnancy shapes the process of
      pregnant embodiment and women's experiences postpartum. Analyzing interviews with
      42 pregnant women and new mothers, I show that while women's experiences of
      pregnant embodiment are shaped by biomedical notions of pregnancy, women also
      bring new meaning to the biomedical guidelines. Women view pregnancy as a process
      of sharing their bodies with their children, and they continue to share their
      bodies with their newborns during the postpartum period. I conclude the paper by
      reflecting on the role of the body in shaping our understanding of medicalized
      phenomena. 

PMID- 24289945
TI  - Comparing approaches to integrating refugee and asylum-seeking healthcare
      professionals in Canada and the UK.
AB  - In this paper, we examine barriers to the integration of refugee doctors and
      nurses in Canada and the United Kingdom. Key obstacles impeding the integration
      of internationally trained health professionals are well documented, but less
      attention has been paid to the integration of refugee health professionals,
      particularly in Canada. Based on documentary analysis and semi-structured
      interviews with 46 Canadian and 34 UK stakeholders, our research shows that there
      are no simple solutions to mitigating the core obstacles that prohibit the
      professional integration of refugee doctors and nurses into host countries. The
      targeted approach adopted in parts of the UK does provide some promising
      practices for Canada, which has yet to develop policies and initiatives specific
      to health professional refugees. This study is intended to contribute to our
      understanding of how immigration and health human resources policies have shaped
      the economic integration of refugee healthcare professionals in the UK and Canada
      in distinct ways. 

PMID- 24289946
TI  - Exploring stigma by association among front-line care providers serving sex
      workers.
AB  - Stigma by association, also referred to as "courtesy stigma," involves public
      disapproval evoked as a consequence of associating with stigmatized persons.
      While a small number of sociological studies have shown how stigma by association
      limits the social support and social opportunities available to family members,
      there is a paucity of research examining this phenomenon among the large network
      of persons who provide health and social services to stigmatized groups. This
      paper presents results from a primarily qualitative study of the work-place
      experiences of a purposive sample of staff from an organization providing
      services to sex workers. The findings suggest that stigma by association has an
      impact on staff health because it shapes both the workplace environment as well
      as staff perceptions of others' support. At the same time, it is evident that
      some staff, owing to their more advantaged social location, are better able to
      manage courtesy stigma than others. 

PMID- 24289947
TI  - Utilization of health resources in South Asian, Chinese and white patients with
      diabetes mellitus.
AB  - AIMS: We sought to determine whether there are differences in health resource
      utilization among South Asian (SA), Chinese and White patients with newly
      diagnosed diabetes mellitus. METHODS: We used province-wide administrative data
      from British Columbia, Canada (1997-2006) to determine proportion of patients
      with >=2 visits/year for all outpatient and family physician (FP) visits,
      proportion of patients with at least one annual visit to specialists,
      ophthalmology/optometry and hospital admissions by ethnic group. RESULTS: There
      were 9529 South Asian, 14,084 Chinese and 143,630 White patients with newly
      diagnosed diabetes in the study. Over 90% of each of the ethnic groups visited
      their FP >=2 visits/year. Chinese patients were less likely to visit FP,
      ophthalmology/optometrists and specialists compared to White patients. SA
      patients had fewer ophthalmology/optometry visits compared to White populations.
      White patients had higher rates of hospitalization. CONCLUSION: Although all
      groups had high proportion of patients with appropriate frequency of FP visits,
      other aspects of health care utilization varied significantly by ethnicity.

PMID- 24289948
TI  - Evaluating the environmental impact of artificial sweeteners: a study of their
      distributions, photodegradation and toxicities.
AB  - While having a long tradition as safe food additives, artificial sweeteners are a
      newly recognized class of environmental contaminants due to their extreme
      persistence and ubiquitous occurrence in various aquatic ecosystems. Resistant to
      wastewater treatment processes, they are continuously introduced into the water
      environments. To date however, their environmental behavior, fate as well as long
      term ecotoxicological contributions in our water resources still remain largely
      unknown. As a first step in the comprehensive study of artificial sweeteners,
      this work elucidates the geographical/seasonal/hydrological interactions of
      acesulfame, cyclamate, saccharin and sucralose in an open coast system at an
      estuarine/marine junction. Higher occurrence of acesulfame (seasonal average:
      0.22 MUg L(-1)) and sucralose (0.05 MUg L(-1)) was found in summer while
      saccharin (0.11  MUg L(-1)) and cyclamate (0.10 MUg L(-1)) were predominantly
      detected in winter. Seasonal observations of the four sweeteners suggest strong
      connections with the variable chemical resistance among different sweeteners. Our
      photodegradation investigation further projected the potential impact of
      persistent acesulfame and sucralose compounds under prolonged exposure to
      intensive solar irradiation. Real-time observation by UPLC-ESI/MS of the
      degradation profile in both sweeteners illustrated that formation of new photo by
      products under prolonged UV irradiation is highly viable. Interestingly, two
      groups of kinetically behaved photodegradates were identified for acesulfame, one
      of which was at least six times more persistent than the parent compound. For the
      first time, acute toxicity for the degradates of both sweeteners were arbitrarily
      measured, revealing photo-enhancement factors of 575 and 17.1 for acesulfame and
      sucralose, respectively. Direct comparison of photodegradation results suggests
      that the phototoxicity of acesulfame degradation products may impact aquatic
      ecosystems. In an attempt to neutralize this prolonged environmental threat, the
      feasibility of UV/TiO2 as an effective mineralization process in wastewater
      treatment was evaluated for both sweeteners. Under an environmental and technical
      relevant condition, a >84% removal rate recorded within 30 min and complete
      photomineralization was achieved within 2 h and delivering the best cost
      efficiency comparing to existing removal methods. A compilation of distribution,
      degradation, toxicity and attenuation results presented in this paper will go
      through critical discussions to explore some current issues and to pinpoint
      solutions for a better control in the emergent contamination of artificial
      sweeteners. 

PMID- 24289949
TI  - Efficacy of single-chamber microbial fuel cells for removal of cadmium and zinc
      with simultaneous electricity production.
AB  - Simultaneous high power generation (3.6 W/m(2)) and high Cd (90%) and Zn (97%)
      removal efficiencies were demonstrated in a single chamber air-cathode microbial
      fuel cell (MFC). The maximum tolerable concentrations (MTCs) were estimated as
      200 MUM for Cd and 400 MUM for Zn. Increasing the concentrations of Cd to 300 MUM
      and Zn to 500 MUM resulted in voltage drops by 71 and 74%, respectively. Feeding
      the MFCs with incrementally increased Cd and Zn concentrations resulted in much
      slower reduction in voltage output. Biosorption and sulfides precipitation are
      the major mechanisms for the heavy metal removal in the MFCs. 

PMID- 24289950
TI  - Effect of oxidant exposure on the release of intracellular microcystin, MIB, and
      geosmin from three cyanobacteria species.
AB  - The release of intracellular microcystin-LR (MC-LR), 2-methylisoborneol (MIB),
      and geosmin was investigated after the oxidation of three cyanobacteria
      (Microcystis aeruginosa (MA), Oscillatoria sp. (OSC), and Lyngbya sp. (LYN)).
      During the oxidation of 200,000 cells/mL of MA, release of intracellular MC-LR
      exceeded the World Health Organization (WHO) guideline of 1 MUg/L during the
      lowest oxidant exposures (CT) tested: ozone (0 mg-min/L, below the ozone demand),
      chlorine (<40 mg-min/L), chlorine dioxide (<560 mg-min/L), and chloramine (<640
      mg-min/L). As the CT increased, ozone, chlorine, and chlorine dioxide were able
      to oxidize the released MC-LR. During the oxidation of OSC (2800 cells/mL) and
      LYN (1600 cells/mL), release of intracellular MIB and geosmin exceeded reported
      threshold odor values after exposure to chlorine, chlorine dioxide, and
      chloramine, which have low reactivity with these taste and odor compounds. Ozone
      oxidation of OSC yielded an increase in MIB concentration at lower exposures
      (<=2.9 mg-min/L), likely due to insufficient oxidation by hydroxyl radicals. The
      release of intracellular organic matter (IOM) was also measured to determine the
      potential of bulk measurements to act as a surrogate for cyanotoxins and
      metabolite release. In all cases, the dissolved organic carbon (DOC) release was
      less than 0.25 mgC/L, which lacked the sensitivity to indicate the release of MC
      LR, MIB, or geosmin. The fluorescence index proved to be a more sensitive
      indicator of intracellular organic matter release than DOC for MA. These results
      illustrate that toxic or odorous compounds may be released from cyanobacteria
      cells during oxidation processes with minimal changes in the DOC concentration. 

PMID- 24289951
TI  - It's a dog's life.

PMID- 24289952
TI  - [Post-traumatic transiliac hernia].

PMID- 24289953
TI  - [Ethics, new ways of dying and organ donation].

PMID- 24289954
TI  - A new thoracic interfascial plane block as anesthesia for difficult weaning due
      to ribcage pain in critically ill patients.

PMID- 24289955
TI  - The role of aquatic ecosystems as reservoirs of antibiotic resistance.
AB  - Although antibiotic resistance has become a major threat to human health
      worldwide, this phenomenon has been largely overlooked in studies in
      environmental settings. Aquatic environments may provide an ideal setting for the
      acquisition and dissemination of antibiotic resistance, because they are
      frequently impacted by anthropogenic activities. This review focuses primarily on
      the emergence and dissemination of antibiotic resistance in the aquatic
      environment, with a special emphasis on the role of antibiotic resistance genes. 

PMID- 24289956
TI  - Diagnostic value of IgG4 Indices in IgG4-related hypertrophic pachymeningitis.
AB  - Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on
      meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are
      lacking. Here, we determined whether IgG4 intrathecal production could
      distinguish IgG4-HP from other disorders presenting with HP (OHP). In patients
      with IgG4-HP, the median CSF IgG4 concentration, IgG4 Index and IgG4Loc were
      significantly higher than in both controls and OHP. CSF IgG4 levels higher than
      2.27mg/dL identified 100% of IgG4-HP and 5% of OHP. An IgG4Loc cut-off of 0.47
      identified 100% of IgG4-HP and no cases of OHP. Our results support CSF IgG4
      quantification and IgG4 Indices as alternatives to meningeal biopsy for the
      diagnosis of IgG4-HP when this procedure is contraindicated or uninformative. 

PMID- 24289957
TI  - A case of fulminant neuromyelitis optica presenting with destructive lesions in
      whole-brain.

PMID- 24289958
TI  - Non-motor symptoms in patients with Parkinson's disease by using self-reported
      and clinician-administered questionnaires.

PMID- 24289959
TI  - The hypouricemiant effect of leflunomide.

PMID- 24289960
TI  - A severe Whipple disease with an immune reconstitution inflammatory syndrome: an
      additional case of thalidomide efficiency.
AB  - We report the case of a 38-year-old man who presented with severe diarrhea,
      weight loss of 10 kg, ankles paresthesia and severe motor weakness in the left
      fibular nerve territory after introduction of azathioprine and corticosteroid for
      proteinuria. Coloscopy and gastroscopy revealed a typical aspect of Whipple
      disease (WD), associated with both positive PAS staining and specific
      immunohistochemistry. T. whipplei PCR results were positive in blood, faeces,
      saliva and duodenal biopsy specimens. Diagnosis of WD with systemic
      manifestations was retained and doxycycline plus hydroxychloroquine therapy were
      started. This treatment improved joint pain, and skin and intestinal symptoms.
      One month later, our patient presented with fever and an important inflammatory
      syndrome (CRP 150 mg/dL and 16.8 10(9)/L leukocytes), while no infection was
      found despite a thorough review. We concluded it was an immune reconstitution
      inflammatory syndrome (IRIS). Manifestations persisted despite increasing
      corticosteroids and thalidomide (200 mg/day) was introduced with good efficacy on
      these symptoms. WD may be revealed by non-specific symptoms such as weight loss
      or arthralgia, but also by many other misleading signs. Our observation
      illustrates the highly polymorphic clinical presentation of WD, and the
      diagnostic difficulties that may arise. This is also a new report of thalidomide
      effectiveness in IRIS in WD.

PMID- 24289961
TI  - Sarcoidosis induced by TNFalpha antagonists. Comments about the article by Vigne
      et al. (Joint Bone Spine 2013;80:104-7).

PMID- 24289962
TI  - HTLV-1-associated arthropathy treated with anti-TNF-alpha agent.
AB  - Human T cell leukemia virus type 1 or HTLV-1 infection is a public health problem
      in endemic regions like Japan, Central America or Africa. Although the majority
      of HTLV-1 carriers remain asymptomatic throughout their lives, some patients
      could develop neurological disorder, inflammatory arthropathy also called HTLV-1
      associated arthropathy or T-cell malignancy, the adult T-cell leukemia/lymphoma
      or ATL with a very poor prognosis. Described to be very close to rheumatoid
      arthritis, HTLV-1-associated arthropathy patients have few or no response to the
      first line therapy with corticosteroids and disease modifying antirheumatic drugs
      or DMARDs. The use of anti-TNF-alpha agents in these patients is an interesting
      alternative but asks the question of risk of developing an adult T-Cell
      leukemia/lymphoma. We reported an exceptional case of a smoldering ATL patient
      with an HTLV-1-associated arthropathy, refractory to corticosteroid, DMARDs and
      rituximab therapy, treated successfully with etanercept, without progression to
      aggressive ATL after 5 years. 

PMID- 24289963
TI  - Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a
      population-based case-control study.
AB  - Few population-based data are available on factors associated with pneumonic and
      ulceroglandular type B tularaemia. We conducted a case-control study during a
      large epidemic in 2000. Laboratory-confirmed case patients were identified
      through active surveillance and matched control subjects (age, sex, residency)
      from the national population information system. Data were collected using a self
      administered questionnaire. A conditional logistic regression model addressing
      missing data with Bayesian full-likelihood modelling included 227 case patients
      and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9.2,
      95% confidence interval (CI) 4.4-22, population-attributable risk (PAR) 82%] and
      farming activities (aOR 4.3, 95% CI 2.5-7.2, PAR 32%) were independently
      associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR
      6.6, 95% CI 1.9-25.4, PAR 48%) was associated with pneumonic tularaemia. Although
      the bulk of tularaemia type B disease burden is attributable to mosquito bites,
      risk factors for ulceroglandular and pneumonic forms of tularaemia are different,
      enabling targeting of prevention efforts accordingly.

PMID- 24289964
TI  - From the Editor-in-Chief.

PMID- 24289965
TI  - The Bone and Joint Decade (BJD) initiative: how did Kuwait perform?
AB  - BACKGROUND: The World Health Organization proclaimed the period between 2000 and
      2010 as the Bone and Joint Decade (BJD). The BJD initiative set out to raise
      awareness regarding increasing incidence of musculoskeletal (MSK) conditions. The
      objective of this study was to assess the degree to which the BJD goals were met
      in Kuwait. METHODS: A gap analysis methodology was used to identify differences
      between the ideal state, defined as achieving the BJD goals, and the current
      state, defined as the extent to which BJD goals were achieved. RESULTS: Our gap
      analysis indicated that the majority of the BJD targets were not met in Kuwait;
      however, given the rising assumed incidence and prevalence of MSK disorders in
      Kuwait, it is critical to outline mechanisms for moving forward. CONCLUSIONS: The
      BJD goals are reachable in Kuwait. Attaining them requires a strong and
      sustainable commitment at many levels of government, provider organizations and
      the research community.

PMID- 24289966
TI  - Preventing malnutrition in children under two (PM2A): a case study in the food
      insecure context of South Sudan.
AB  - Prevention of malnutrition for children under two (PM2A) is a new approach being
      used by the United States Agency for International Development (USAID). Since
      2010, PM2A has been adopted on a widespread basis in food assistance programs
      with the aim of preventing chronic malnutrition (stunting) in non-emergency
      settings. This case study uses mixed methods to document household food sources,
      insecurity and ration receipt within the context of a multi-year health and
      nutrition program implemented in South Sudan. Evidence from the program, which
      included a PM2A component in addition to health, empowerment and household
      agricultural interventions, indicates that household food security remained poor
      despite ration receipt. While PM2A is a relatively new strategy and efforts are
      under way to evaluate outcomes, more evidence is needed to determine the
      appropriateness of the PM2A approach in highly food insecure contexts and to
      establish the range of contexts in which PM2A is a choice approach for food
      assistance programs. 

PMID- 24289967
TI  - Factors influencing motivation and retention of primary healthcare workers in the
      rural areas of Oyo State, Nigeria.
AB  - BACKGROUND: Limited data exist on retention of primary healthcare (PHC) staff in
      rural areas, crippling the already fragile healthcare systems in Nigeria. This
      study investigated why PHC staff would or would not want to work in rural areas
      and how they could be retained. METHODS: Four hundred and twelve (412) health
      workers and caregivers, and 21 key informants were interviewed in Ona-Ara LGA.
      Logistic regression statistics was used to analyse quantitative data and
      narrative for qualitative data. RESULTS: There was no significant factor
      influencing health workers' unwillingness to work in rural areas and,
      relationship between their demographic characteristics and perceived reasons to
      do so. Combined factors influencing PHC workers' willingness to work in rural
      areas influenced use of PHC. CONCLUSION: Financial and non-financial incentives
      are responsible for workers' motivation to work in rural areas. The mal
      distribution of health facilities and health workers between urban and rural
      areas must be addressed.

PMID- 24289968
TI  - Does health insurance ensure equitable health outcomes? An analysis of hospital
      services usage in urban India.
AB  - In this paper, we examine the relationship between socio-economic status (SES)
      and the usage of in-patient services, and analyze the impact of introducing
      health insurance in India - a major developing country with poor health outcomes.
      In contrast to results of similar works undertaken for developed countries, our
      results reveal that the positive relation between usage of in-patient services
      and SES persists even in the presence of health insurance. This implies that
      health insurance is unable to eliminate the inequities in accessing healthcare
      services that stem from disparities in SES. In fact, insurance aggravates
      inequity in the healthcare market. The study is based on unit-level data from the
      2005-06 Morbidity and Health Care Survey undertaken by National Sample Survey
      Organization. 

PMID- 24289969
TI  - Modulatory effect of neoadjuvant chemotherapy on biomarkers expression;
      assessment by digital image analysis and relationship to residual cancer burden
      in patients with invasive breast cancer.
AB  - The use of digital imaging techniques for biomarker assessment has gained
      recognition as a valid tool for clinical use. In this study, we used image
      analysis for evaluation of estrogen receptor (ER), progesterone receptor (PR),
      human epidermal growth factor receptor (HER2), Ki-67 index, and p53 in 172
      patients with invasive breast cancer treated with neoadjuvant chemotherapy and
      compared it with an untreated group (100 cases). We also examined the
      relationship between biomarker expression and the extent of residual disease
      using the Web-based MD Anderson residual cancer burden (RCB) calculator. Residual
      disease was classified as RCB 0/I, II, and III corresponding to complete/near
      complete response, moderate, and extensive residual disease, respectively.
      Overall change in ER, PR, and HER2 status in the treated group was seen in 9.02%
      (P = .0148), 18.4% (P = .011), and 12.0% (P = .0042), respectively. Change in
      HER2 status, positive to negative and negative to positive, occurred in 27.2% and
      7.0%, respectively. The group with RCB 0/I was frequently younger (P = .0057) and
      showed higher ER(-) status (P = .0316), lower ER scores (P = .0103), higher Ki-67
      index (P = .0008), and p53 (P = .0055) compared with those with RCB II and III.
      Pathologic tumor stage (P = .0072), lumpectomy versus mastectomy (P = .0048), and
      p53 expression (P = .0190) were independent predictors of recurrence-free
      survival. The RCB categories (P = .0003) and tumor grade (P = .0049) were
      independent predictors of overall survival. This is the first study to conduct a
      comprehensive analysis of biomarkers in neoadjuvant chemotherapy-treated patients
      versus an untreated group using the digital image analysis method. We have
      demonstrated for the first time the relationship between RCB, tumor biomarkers
      expression, and clinical outcome. 

PMID- 24289970
TI  - Activating transcription factor 2 in mesenchymal tumors.
AB  - Activating transcription factor 2 (ATF2) is a member of activator protein 1
      superfamily, which can heterodimerize with other transcription factors regulating
      cell differentiation and survival. ATF2 assembles into a complex with the
      synovial sarcoma translocation, chromosome 18 (SS18)-synovial sarcoma, X
      breakpoint (SSX) fusion oncoprotein, and the transducin-like enhancer of split 1
      (TLE1) corepressor, driving oncogenesis in synovial sarcoma. The fusion
      oncoproteins in many other translocation-associated sarcomas incorporate
      transcription factors from the ATF/cAMP response element binding or E26 families,
      which potentially form heterodimers with ATF2 to regulate transcription. ATF2 may
      therefore play an important role in the oncogenesis of many mesenchymal tumors,
      but as yet, little is known about its protein expression in patient specimens.
      Herein we perform immunohistochemical analyses using a validated specific
      antibody for ATF2 expression and intracellular localization on a cohort of 594
      malignant and 207 benign mesenchymal tumors representing 47 diagnostic entities.
      Melanoma served as a positive control for nuclear and cytoplasmic staining. High
      nuclear ATF2 expression was mainly observed in translocation-associated and/or
      spindle cell sarcomas including synovial sarcoma, desmoplastic small round cell
      tumor, endometrial stromal sarcoma, gastrointestinal stromal tumor, malignant
      peripheral nerve sheath tumor, and solitary fibrous tumor. Cytoplasmic ATF2
      expression was less frequently seen than nuclear expression in malignant
      mesenchymal tumors. Benign mesenchymal tumors mostly showed much lower nuclear
      and cytoplasmic ATF2 expression. 

PMID- 24289971
TI  - Mononeuritis multiplex with tumefactive cellular infiltration in a patient with
      reactive lymphoid hyperplasia with increased immunoglobulin G4-positive cells.
AB  - We describe a 54-year-old man with mononeuritis multiplex and reactive lymphoid
      hyperplasia with increased immunoglobulin G4 (IgG4)-positive cells. Asymmetrical
      numbness and weakness had advanced stepwise for 6 years. Serum immunoglobulin G,
      IgG4, and immunoglobulin E levels were elevated, whereas M protein was not
      detected. Chest and abdominal computed tomography showed generalized
      lymphadenopathy. Inguinal lymph node biopsy revealed expansion of the
      interfollicular area with infiltration of IgG4-positive cells, of which the
      absolute number was greater than 100 per high-power field, and the percentage of
      IgG4+/immunoglobulin G+ plasma cells was 33%. Sural nerve biopsy disclosed axonal
      neuropathy with tumefactive lymphoid infiltrate in epineurium, but IgG4-positve
      plasma cells and fibrosis were not detected. Symptoms and laboratory data were
      improved with oral glucocorticoid therapy at a dose of 0.6 mg/kg per day.
      Although the causal mechanisms of neuropathy should be determined in future
      studies, peripheral nerve involvement may occur in patients with reactive
      lymphoid hyperplasia with increased IgG4-positive cells. 

PMID- 24289972
TI  - Histologic grading based on counting poorly differentiated clusters in
      preoperative biopsy predicts nodal involvement and pTNM stage in colorectal
      cancer patients.
AB  - Histologic grading is commonly assessed in colorectal cancer preoperative
      biopsies. Nevertheless, its clinical impact is limited by low interobserver
      reproducibility and poor concordance with grading found in the final resection
      specimen. In the present study, we aimed to investigate the reproducibility,
      accuracy, and predictive value on lymph node status or pTNM stage of a novel
      grading system based on the number of poorly differentiated clusters in
      colorectal cancer preoperative endoscopic biopsies. Grading based on counting
      poorly differentiated clusters was assessed in 163 colorectal cancer endoscopic
      biopsies and corresponding surgical specimens. With this system, 152 biopsies
      could be graded with good interobserver agreement (kappa = 0.735). In comparison
      with the surgical specimens, 75% of colorectal cancers were correctly graded in
      the biopsy, and 81% of poorly differentiated colorectal cancers were identified
      at initial biopsy. High poorly differentiated clusters grade in the biopsy was
      significantly associated with nodal metastasis, high pTNM stage (P < .0001), or
      histologic features suggestive of more aggressive behavior (tumor budding,
      perineural invasion, vascular invasion, and infiltrating tumor border) in the
      surgical specimen. Furthermore, this system identified colorectal cancer with
      nodal involvement or high pTNM stage with a 78% positive predictive value and 71%
      and 69% negative predictive values, respectively. Our findings suggest that a
      grading system based on the quantification of poorly differentiated clusters is
      feasible in most colorectal cancer endoscopic biopsies. In view of its good
      reproducibility, accuracy, and predictive value on the anatomical extent of the
      disease, it may be taken into account for decision-making in colorectal cancer
      treatment. 

PMID- 24289973
TI  - Should blood donors be routinely screened for glucose-6-phosphate dehydrogenase
      deficiency? A systematic review of clinical studies focusing on patients
      transfused with glucose-6-phosphate dehydrogenase-deficient red cells.
AB  - The risk factors associated with the use of glucose-6-phosphate dehydrogenase
      (G6PD)-deficient blood in transfusion have not yet been well established.
      Therefore, the aim of this review was to evaluate whether whole blood from
      healthy G6PD-deficient donors is safe to use for transfusion. The study undertook
      a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and
      CINHAL, with no date restriction up to March 2013, as well as those included in
      articles' reference lists and those included in Google Scholar. Inclusion
      criteria required that studies be randomized controlled trials, case controls,
      case reports, or prospective clinical series. Data were extracted following the
      Preferred Reporting Items for Systematic Reviews using a previously piloted form,
      which included fields for study design, population under study, sample size,
      study results, limitations, conclusions, and recommendations. The initial search
      identified 663 potentially relevant articles, of which only 13 studies met the
      inclusion criteria. The reported effects of G6PD-deficient transfused blood on
      neonates and children appear to be more deleterious than effects reported on
      adult patients. In most cases, the rise of total serum bilirubin was abnormal in
      infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after
      transfusion. All studies on neonates and children, except one, recommended a
      routine screening for G6PD deficiency for this at-risk subpopulation because
      their immature hepatic function potentially makes them less able to handle any
      excess bilirubin load. It is difficult to make firm clinical conclusions and
      recommendations given the equivocal results, the lack of standardized evaluation
      methods to categorize red blood cell units as G6PD deficient (some of which are
      questionable), and the limited methodological quality and low quality of
      evidence. Notwithstanding these limitations, based on our review of the available
      literature, there is little to suggest that G6PD-deficient individuals should be
      excluded from donating red blood cells, although transfusions of such blood may
      potentially have negative impacts on premature neonates or patients who need
      repeated transfusions, and thus, for this group, screening for G6PD deficiency
      may be appropriate. 

PMID- 24289974
TI  - VitaminA, E, and D deficiencies in tunisian very low birth weight neonates:
      prevalence and risk factors.
AB  - BACKGROUND: Preterm neonates are at high risk of vitamin deficiencies, which may
      expose them to increased morbidity and mortality. This study aimed to determine
      the prevalence and risk factors for vitamin A, E, and D deficiencies in Tunisian
      very low birth weight (VLBW) neonates. METHODS: A total of 607 VLBW and 300 term
      neonates were included in the study. Plasma vitamins A and E were assessed by
      high performance liquid chromatography and vitamin D was assessed by
      radioimmunoassay. RESULTS: Prevalence of vitamin A, E, and D deficiencies were
      dramatically elevated in VLBW neonates and were significantly higher than term
      neonates (75.9% vs. 63.3%; 71.3% vs. 55.5%; and 65.2% vs. 40.4%, respectively).
      In VLBW neonates, the prevalence of vitamin deficiencies was significantly higher
      in lower classes of gestational age and birth weight. Vitamin E deficiency was
      associated with pre-eclampsia [odds ratio (OR) (95% confidence interval, 95% CI),
      1.56 (1.01-2.44); p < 0.01] and gestational diabetes [4.01 (1.05-17.0); p <
      0.01]. Vitamin D deficiency was associated with twin pregnancy [OR (95% CI), 2.66
      (1.33-5.35); p < 0.01] and pre-eclampsia [2.89 (1.36-6.40); p < 0.01].
      CONCLUSION: Vitamin A, E, and D deficiencies are very common in Tunisian VLBW
      neonates and are associated with pre-eclampsia. Improved nutritional and health
      support for pregnant women and high dose vitamins A, E, and D supplementation in
      VLBW neonates are strongly required in Tunisia.

PMID- 24289975
TI  - Histological chorioamnionitis and neonatal outcome in preterm infants.

PMID- 24289976
TI  - The difference between temperate and tropical saltwater species' acute
      sensitivity to chemicals is relatively small.
AB  - Due to a lack of saltwater toxicity data in tropical regions, toxicity data
      generated from temperate or cold water species endemic to North America and
      Europe are often adopted to derive water quality guidelines (WQG) for protecting
      tropical saltwater species. If chemical toxicity to most saltwater organisms
      increases with water temperature, the use of temperate species data and
      associated WQG may result in under-protection to tropical species. Given the
      differences in species composition and environmental attributes between tropical
      and temperate saltwater ecosystems, there are conceivable uncertainties in such
      'temperate-to-tropic' extrapolations. This study aims to compare temperate and
      tropical saltwater species' acute sensitivity to 11 chemicals through a
      comprehensive meta-analysis, by comparing species sensitivity distributions
      (SSDs) between the two groups. A 10 percentile hazardous concentration (HC10) is
      derived from each SSD, and then a temperate-to-tropic HC10 ratio is computed for
      each chemical. Our results demonstrate that temperate and tropical saltwater
      species display significantly different sensitivity towards all test chemicals
      except cadmium, although such differences are small with the HC10 ratios ranging
      from 0.094 (un-ionised ammonia) to 2.190 (pentachlorophenol) only. Temperate
      species are more sensitive to un-ionised ammonia, chromium, lead, nickel and
      tributyltin, whereas tropical species are more sensitive to copper, mercury,
      zinc, phenol and pentachlorophenol. Through comparison of a limited number of
      taxon-specific SSDs, we observe that there is a general decline in chemical
      sensitivity from algae to crustaceans, molluscs and then fishes. Following a
      statistical analysis of the results, we recommend an extrapolation factor of two
      for deriving tropical WQG from temperate information. 

PMID- 24289977
TI  - Photodegradation of sulfapyridine under simulated sunlight irradiation: kinetics,
      mechanism and toxicity evolvement.
AB  - In this study, the photoinduced degradation of sulfapyridine (SPY) was
      investigated under simulated light irradiation (lambda>200nm). The effect of pH
      and main water constituents including nitrate ion, bicarbonate, dissolved organic
      matter (DOM) and iron(III) on the photodegradation was explored. SPY was
      effectively removed in aqueous solution at pH 8 under UV-vis irradiation, with
      removal efficiency of 100% within 120min. DOM and iron(III) had retarding
      influence on the SPY removal, whereas nitrate ion and bicarbonate did not show
      any obvious effect. Under UV-vis irradiation, the formation of singlet oxygen
      ((1)O2) accelerated the SPY photodegradation and the contribution of indirect
      photolysis due to reaction with (1)O2 was up to 42%. The transformation products
      of SPY were identified by HPLC-MS and the possible photoreaction pathways were
      proposed. It showed that photoinduced hydrolysis, photo-oxidation via (1)O2 and
      desulfonation were the main degradation ways for SPY decomposition. Toxicity
      assays by Vibrio fischeri proved that the transformation products were more toxic
      than the parent compound. 

PMID- 24289978
TI  - Analysis of anthelmintics in surface water by ultra high performance liquid
      chromatography coupled to quadrupole linear ion trap tandem mass spectrometry.
AB  - A method based on ultra high performance liquid chromatography coupled to
      quadrupole linear ion trap mass spectrometry (UHPLC-QqLIT-MS) has been developed
      to investigate occurrence of 10 anthelmintic drugs from different structural
      groups (moxidectin, flubendazole, fenbendazole, levamisol, mebendazole,
      oxibendazole, albendazole, triclabendazole, febantel and praziquantel) in surface
      water. Analytes were pre-concentrated by solid phase extraction (SPE) using
      hydrophilic-lipophilic polymeric based sorbent. Quantification of investigated
      analytes was done using deuterated compounds as internal standards in order to
      minimize matrix effect. Analyte recoveries from spiked samples at two
      concentration levels were above 75% for most of the analytes. The main advantages
      of developed method are fast separation using UHPLC and therefore short analysis
      time, combined with good sensitivity which is demonstrated by low ngL(-1)
      detection limits. The developed method was applied for analysis of anthelmintics
      in the Llobregat River (NE Spain) and its main tributaries (rivers Anoia and
      Cardener). Eight out of ten anthelmintics were detected in all analyzed samples
      with the concentrations in low ngL(-1) level. The method fills the gap on
      analytical methodologies for determination of anthelmintic drugs in the
      environment. 

PMID- 24289979
TI  - Effect of organic matter and calcium carbonate on behaviors of cadmium adsorption
      desorption on/from purple paddy soils.
AB  - Batch experiments and sequential extraction analysis were employed to investigate
      the effects of soil organic matter and CaCO3 on the adsorption and desorption of
      cadmium (Cd(2+)) onto and from two purple paddy soils, an acidic purple paddy
      soil (APPS) and a calcareous purple paddy soil (CPPS). The Cd(2+) adsorption
      isotherms on both soils could be well-described by the Langmuir and Freundlich
      equations. CPPS had a higher capacity and a stronger affinity for Cd(2+)
      adsorption compared with APPS. The adsorption process of Cd(2+) on APPS was
      dominated by electrostatic attractions, whereas the adsorption mechanism varied
      depending on the Cd(2+) concentrations in equilibrium solutions on CPPS. At low
      equilibrium concentrations, the adsorption process was primarily specific
      adsorption, but nonspecific adsorption dominated at high equilibrium
      concentrations. Removal of organic matter decreased the amount of Cd(2+)
      adsorption on both of the soils, slightly affected the Cd(2+) desorption rate and
      exchangeable Cd (EXC-Cd) in APPS and increased the desorption rate and EXC-Cd in
      CPPS, suggesting that the effect of organic matter on Cd(2+) adsorption
      desorption depends on the soils. CPPS and APPS containing CaCO3 exhibited higher
      adsorption amounts but lower desorption rates and lower proportions of EXC-Cd
      than those of their corresponding soils without CaCO3, demonstrating that CaCO3
      played an important role in Cd(2+) specific adsorption on soil. The changes in
      the thermodynamic parameters, including free energy (DeltaG(0)), enthalpy
      (DeltaH(0)) and entropy (DeltaS(0)), as evaluated by the Van't Hoff equations,
      indicated that the adsorption was a spontaneous and endothermic process with the
      primary interaction forces of dipole interactions and hydrogen bonds on APPS,
      whereas both physical and chemical interactions dominated the adsorption on CPPS.

PMID- 24289980
TI  - Effects of condensed organic matter on PCBs bioavailability in juvenile swine, an
      animal model for young children.
AB  - The exposure assessment of polychlorinated biphenyls (PCBs) contaminated soils is
      a critical issue in terms of human health, especially since little reliable
      information on transfer of PCBs to humans via involuntary soil ingestion is
      available. Indeed, young children with their hand-to-mouth activity may be
      exposed to contaminated soils. The current study addresses the impact of soil
      organic matter (OM) condensation on bioavailability of sequestrated NDL-PCBs.
      Three artificial soils (ASs) were prepared according to OECD guideline 207. One
      standard soil (SS), devoid of OM, and two amended versions of this SS with fulvic
      acid (FA) or activated carbon (AC) were prepared to obtain 1% organic mass. This
      study involved fourteen juvenile male swine as a digestive physiology model of
      young children. Animals were randomly distributed into 4 contaminated groups (3
      replicates) and a control one (2 replicates). During 10d, the piglets were fed AS
      or a corn oil spiked with 19200 ng of Aroclor 1254 per g of dry matter (6000 ng
      g(-1) of NDL-PCBs) to achieve an exposure dose of 1200 ng NDL-PCBskg(-1) of body
      weight per day. After 10d of oral exposure, NDL-PCBs in adipose tissue, liver and
      muscles were analyzed by GC-MS, after extraction and purification. Two distinct
      groups of treatments were found: on the one hand oil, SS and FA, on the other
      hand C and AC. This study highlights that condensed OM (AC) strongly reduces
      bioavailability whereas the less condensed one (FA) does not seem to have a
      significant effect. This result has to be considered as a first major step for
      further relative bioavailability studies involving mixture of different humic
      substances.

PMID- 24289981
TI  - Effects of plant growth-promoting bacteria isolated from copper tailings on
      plants in sterilized and non-sterilized tailings.
AB  - Ten strains of Cu-tolerant bacteria with potential plant growth-promoting ability
      were isolated by selecting strains with the ability to use 1-aminocyclopropane-1
      carboxylate as a sole nitrogen source (designated ACC-B) or fix nitrogen
      (designated FLN-B) originating from the rhizosphere of plants growing on copper
      tailings. All 10 strains proved to have intrinsic ability to produce indole
      acetic acid and siderophores, and most of them could mobilize insoluble
      phosphate. In addition, a greenhouse study showed that ACC-B, FLN-B and a mixture
      of both had similar, potent ability to stimulate growth of Pennisetum purpureum,
      Medicago sativa and Oenothera erythrosepala plants grown on sterilized tailings.
      For instance, above-ground biomass of P. purpureum was 278-357% greater after 60d
      growth on sterilized tailings in their presence. They could also significantly
      promote the growth of the plants grown on non-sterilized tailings, though the
      growth-promoting effects were much weaker. So, strategies for using of the plant
      growth-promoting bacteria in the practice of phytoremediation deserve further
      studies to get higher growth-promoting efficiency. 

PMID- 24289982
TI  - Biochar as a sorbent for contaminant management in soil and water: a review.
AB  - Biochar is a stable carbon-rich by-product synthesized through
      pyrolysis/carbonization of plant- and animal-based biomass. An increasing
      interest in the beneficial application of biochar has opened up multidisciplinary
      areas for science and engineering. The potential biochar applications include
      carbon sequestration, soil fertility improvement, pollution remediation, and
      agricultural by-product/waste recycling. The key parameters controlling its
      properties include pyrolysis temperature, residence time, heat transfer rate, and
      feedstock type. The efficacy of biochar in contaminant management depends on its
      surface area, pore size distribution and ion-exchange capacity. Physical
      architecture and molecular composition of biochar could be critical for practical
      application to soil and water. Relatively high pyrolysis temperatures generally
      produce biochars that are effective in the sorption of organic contaminants by
      increasing surface area, microporosity, and hydrophobicity; whereas the biochars
      obtained at low temperatures are more suitable for removing inorganic/polar
      organic contaminants by oxygen-containing functional groups, electrostatic
      attraction, and precipitation. However, due to complexity of soil-water system in
      nature, the effectiveness of biochars on remediation of various organic/inorganic
      contaminants is still uncertain. In this review, a succinct overview of current
      biochar use as a sorbent for contaminant management in soil and water is
      summarized and discussed. 

PMID- 24289983
TI  - The relation between cognitive and motor performance and their relevance for
      children's transition to school: a latent variable approach.
AB  - Both theoretically and empirically there is a continuous interest in
      understanding the specific relation between cognitive and motor development in
      childhood. In the present longitudinal study including three measurement points,
      this relation was targeted. At the beginning of the study, the participating
      children were 5-6-year-olds. By assessing participants' fine motor skills, their
      executive functioning, and their non-verbal intelligence, their cross-sectional
      and cross-lagged interrelations were examined. Additionally, performance in these
      three areas was used to predict early school achievement (in terms of
      mathematics, reading, and spelling) at the end of participants' first grade.
      Correlational analyses and structural equation modeling revealed that fine motor
      skills, non-verbal intelligence and executive functioning were significantly
      interrelated. Both fine motor skills and intelligence had significant links to
      later school achievement. However, when executive functioning was additionally
      included into the prediction of early academic achievement, fine motor skills and
      non-verbal intelligence were no longer significantly associated with later school
      performance suggesting that executive functioning plays an important role for the
      motor-cognitive performance link. 

PMID- 24289984
TI  - The Supraspinatus and the Deltoid - not just two arm elevators.
AB  - BACKGROUND: The debate on the clinical and functional role of the Supraspinatus
      in relation to the Deltoid necessitates experimental assessment of their
      contributions to arm elevation. Our goal was to evaluate the responses of both
      muscles to increased elevation moment loading. METHODS: Twenty-three healthy
      volunteers applied 30N elevation forces at the proximal and distal humerus,
      resulting in small and large glenohumeral elevation moment tasks. The responses
      of the Deltoid and Supraspinatus were recorded with surface and fine-wire
      electromyography, quantified by (EMGdistal-EMGproximal), and normalized by the
      summed activations (EMGdistal+EMGproximal) to RMuscle ratios. RESULTS: Deltoid
      activity increased with large elevation moment loading (RDE=.11, 95%-CI [.06
      .16]). Surprisingly, there was no significant average increase in Supraspinatus
      activation (RSSp=.06, 95%-CI [-.08 to .20]) and its response was significantly
      more variable (Levene's test, F=11.7, p<.001). There was an inverse association
      between the responses (beta=-1.02, 95%-CI [-2.37 to .32]), indicating a potential
      complementary function of the Supraspinatus to the Deltoid. CONCLUSION: The
      Deltoid contributes to the glenohumeral elevation moment, but the contribution of
      the Supraspinatus is variable. We speculate there is inter-individual or intra
      muscular function variability for the Supraspinatus, which may be related to the
      frequently reported variations in symptoms and treatment outcome of Supraspinatus
      pathologies.

PMID- 24289985
TI  - Postural leaning direction challenges the manifestation of tendon vibration
      responses at the ankle joint.
AB  - In this study, we examined the interaction between central and peripheral
      proprioceptive afferent pathways by applying ankle tendon vibration during
      postural leaning in different directions. Twenty young participants stood for 60s
      over the midline of two adjacent force platforms in (a) neutral stance
      distributing Body Weight (BW) equally between the platforms, (b) forward leaning
      transferring 80% of BW to the front platform and (c) backward leaning
      transferring 80% of BW to the rear platform. Participants controlled the degree
      of leaning by receiving on-line visual feedback of BW distribution matched to a
      target line. Vibration (80Hz, 1.5-1.8mm) was applied over the Achilles or
      tibialis anterior tendon during the middle 20s of standing. This induced a
      postural shift towards the vibration side and an increase in the variability of
      the BW distribution that was greater in backward compared to forward leaning. EMG
      responses to tendon vibration were independent of the leaning direction.
      Antagonistic activity also increased in response to vibration, the amplitude of
      this increase however was direction dependent. These results favor the hypothesis
      about the central co-modulation of the vibration evoked proprioceptive inflow
      based on postural and visual feedback rather than muscle tension constraints. 

PMID- 24289986
TI  - Learning and transfer in motor-respiratory coordination.
AB  - Motor-respiratory coordination occurs naturally during exercise, but the number
      of coordination patterns performed between movement and breathing is limited. We
      investigated whether participants could acquire novel ratios (either 5:2 or 5:3).
      To examine complex temporal relationships between movement and breathing, we used
      lagged return plots that were produced by graphing relative phase against
      relative phase after a time delay. By the end of practice, participants performed
      5:2 consistently and performed 5:3 using more stable ratios (3:2 and 2:1). Lagged
      return plots revealed that 5:3 learners harnessed the stable inphase and
      antiphase patterns to stabilize the required ratio. That strategy resulted in the
      performance of smaller-integer ratios in the production of 5:3 but not 5:2.
      Despite those differences, there was positive transfer to unpracticed ratios that
      was similar in both learning conditions. The time series analysis of lagged
      return plots revealed differences in ratio performance at transfer. Ratios whose
      component frequencies were farther apart, like 7:2, were performed consistently,
      while ratios whose component frequencies were more similar, like 5:4, elicited
      attraction to inphase and antiphase. The implication is that participants can
      combine more stable chunks of rhythmic behavior to produce more complex ratios. 

PMID- 24289988
TI  - PGJ2 restores RA sensitivity in melanoma cells by decreasing PRAME and EZH2.

PMID- 24289987
TI  - Reprint of: policy decisions on endocrine disruptors should be based on science
      across disciplines: a response to Dietrich et al.

PMID- 24289989
TI  - Dienogest inhibits nerve growth factor expression induced by tumor necrosis
      factor-alpha or interleukin-1beta.
AB  - OBJECTIVE: Dienogest (DNG), a selective P receptor (PR) agonist, is used to treat
      endometriosis. To investigate whether DNG affects nerve growth factor (NGF)
      expression, we stimulated human endometrial epithelial cells (hEECs) with
      inflammatory cytokines. DESIGN: Prospective basic research study using
      immortalized hEEC lines. SETTING: Development Research, Mochida Pharmaceutical
      Co., Ltd., Japan. PATIENT(S): None. INTERVENTION(S): Not applicable. MAIN OUTCOME
      MEASURE(S): In immortalized hEECs, NGF production induced by tumor necrosis
      factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta) was evaluated in the
      presence or absence of the synthetic progestin DNG or endogenous P. The NGF
      messenger RNA (mRNA) and protein were measured using real-time reverse
      transcriptase-polymerase chain reaction (PCR) and ELISA, respectively. The NGF
      bioactivity in the culture medium was measured by assaying neurite outgrowth of
      PC-12 cells. RESULT(S): Tumor necrosis factor-alpha and IL-1beta induced NGF mRNA
      and protein and increased NGF bioactivity in the culture medium. These activities
      were inhibited by DNG in a hEEC line that stably expresses PR. In contrast, in an
      hEEC line that constitutively expresses faint levels of PR, no inhibitory effect
      of DNG on NGF mRNA was detected. The NGF mRNA was also inhibited in hEEC lines
      that express only PR-A or only PR-B. CONCLUSION(S): Nerve growth factor is one of
      the key mediators that generates the pain associated with endometriosis.
      Dienogest inhibits NGF expression through PR-A and PR-B in hEEC, which may
      contribute to the pharmacological mechanisms of how DNG relieves pain in
      endometriosis.

PMID- 24289990
TI  - Placebo effect in fertility: advantageous or false advertisement?

PMID- 24289991
TI  - Evaluation of the transvaginal resection of low-segment cesarean scar ectopic
      pregnancies.
AB  - OBJECTIVE: To evaluate the transvaginal approach for exogenous cesarean scar
      ectopic pregnancy (CSEP) lesion resection, according to our experience. DESIGN:
      Retrospective study. SETTING: University hospital. PATIENT(S): Twenty-three
      patients with confirmed exogenous CSEP treated with transvaginal resection of the
      lesions at the Shengjing Hospital of China Medical University. INTERVENTION(S):
      Lesion resection by the transvaginal approach. MAIN OUTCOME MEASURE(S): Surgery
      time, intraoperative blood loss, postoperative drainage volume, and average days
      of postoperative hospitalization were compared between the transvaginal procedure
      group and the transabdominal procedure group. RESULT(S): Significant differences
      were found. No significant differences were found in the drop of serum hCG level
      after 48 hours and the postoperative recurrence rate between the two groups. The
      rate of successful treatment was 96%. CONCLUSION(S): The transvaginal approach
      for exogenous CSEP lesion resection possesses many advantages. In the hands of a
      skilled surgeon it can readily address the treatment problems posed by an
      exogenous CSEP without imposing an increase in surgical risk or technical
      difficulty.

PMID- 24289992
TI  - Uterus-sparing operative treatment for adenomyosis.
AB  - OBJECTIVE: To review systematically the literature on uterus-sparing surgical
      treatment options for adenomyosis. DESIGN: Systematic literature review. SETTING:
      Tertiary academic center. PATIENT(S): Women with histologically proven
      adenomyosis treated with uterus-sparing surgical techniques. INTERVENTION(S):
      Conservative uterine-sparing surgery for adenomyosis classified as (1) complete
      excision of adenomyosis, (2) cytoreductive surgery or incomplete removal of the
      lesion, or (3) nonexcisional techniques, with studies selected if women with
      adenomyosis were treated surgically without performing hysterectomy. MAIN OUTCOME
      MEASURE(S): The cure rate after interventional strategies, the rate of symptom
      (dysmenorrhea and menorrhagia) control, and pregnancy rate in each group of
      intervention. RESULT(S): A quality assessment tool was used to assess the
      scientific value of each study. In total, 64 studies dealing with 1,049 patients
      were identified. After complete excision, the dysmenorrhea reduction, menorrhagia
      control, and pregnancy rate were 82.0%, 68.8%, and 60.5%, respectively. After
      partial excision, the dysmenorrhea reduction, menorrhagia control, and pregnancy
      rate were 81.8%, 50.0%, and 46.9%, respectively. CONCLUSION(S): Uterine-sparing
      operative treatment of adenomyosis and its variants appear to be feasible and
      efficacious. Well-designed, comparative studies are urgently needed to answer the
      multiple questions arising from this intriguing intervention.

PMID- 24289993
TI  - Are skin scar characteristics associated with the degree of pelvic adhesions at
      laparoscopy?
AB  - OBJECTIVE: To investigate whether individual or a combination of abdominal
      surgical scar characteristics can predict the severity and extent of intra
      abdominal adhesions. DESIGN: A prospective cohort study. SETTING: A tertiary
      referral center in the United Kingdom. PATIENT(S): One hundred women who had
      previously undergone abdominopelvic surgery and were undergoing an elective
      laparoscopic gynecologic operations. INTERVENTION(S): Abdominal scars were
      evaluated preoperatively using the modified Manchester Scar Questionnaire
      Adhesions were assessed intraoperatively and compared with the cutaneous
      findings. MAIN OUTCOME MEASURE(S): Presence and severity of intra-abdominal
      adhesions. RESULT(S): Of 100 women recruited into this study, 71 (71%) women were
      found to have intra-abdominal Aadhesions, and 29 (29%) had no adhesions. Women
      who had more than one abdominal scar, a palpable scar, and/or a longer scar were
      most likely to have pelvic adhesions during the current surgery. Women with the
      highest mean scar scores also had a greater total adhesion score. CONCLUSION(S):
      Adhesions are a common postoperative consequence of open or laparoscopic surgery.
      Skin scar characteristics are associated with the presence and degree of pelvic
      adhesions. Future studies should examine whether these characteristics can be
      used as a preoperative predictive tool to facilitate surgical decision-making and
      elective operating room organization.

PMID- 24289995
TI  - Reply of the authors.

PMID- 24289994
TI  - Identifying women with indicators of subfertility in a statewide population
      database: operationalizing the missing link in assisted reproductive technology
      research.
AB  - OBJECTIVE: To identify a group of deliveries to mothers with indicators of
      subfertility (SUBFERTILITY). DESIGN: Longitudinal cohort study. SETTING:
      Hospital. PATIENT(S): A total of 334,152 deliveries to Massachusetts mothers in a
      Massachusetts hospital between July 1, 2004, and December 31, 2008.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Subfertility was defined by an
      indication on a current or past birth certificate or hospital utilization data of
      infertility or assisted reproductive technology (ART) cycle before index delivery
      and no indication of ART use with index delivery. RESULT(S): Initially, 12,367
      deliveries met the inclusion criteria for SUBFERTILITY (8,019 from birth
      certificates, 2,777 from hospital data, 1,571 from prior ART treatment). Removing
      deliveries from more than one data source resulted in 10,764 unique deliveries.
      Removing deliveries resulting from ART treatments left 6,238 deliveries in the
      SUBFERTILITY category. Demographic analysis indicated that deliveries in
      SUBFERTILITY were more similar to those in the ART population than to those in
      the fertile population. CONCLUSION(S): We have demonstrated the feasibility of
      using existing population-based linked public health data sets to identify
      SUBFERTILITY deliveries, and we have used ART data to distinguish ART and
      SUBFERTILITY births. The SUBFERTILITY category can serve as a comparison group of
      subfertile patients for studies of ART delivery and longitudinal health outcomes.

PMID- 24289996
TI  - Consumer-friendly reporting of in vitro fertilization outcomes.

PMID- 24289997
TI  - Reply of the author.

PMID- 24289998
TI  - Does progesterone elevation compromise pregnancy rates in high responders?
      Insufficient evidence to draw a conclusion.

PMID- 24289999
TI  - Superoxide dismutase-loaded biodegradable nanoparticles targeted with a follicle
      stimulating hormone peptide protect Sertoli cells from oxidative stress.
AB  - OBJECTIVE: To evaluate targeted superoxide dismutase (SOD)-loaded biodegradable
      nanoparticles' (NPs) ability to protect Sertoli cells from hydrogen peroxide
      (H2O2)-induced oxidative stress. DESIGN: Cell culture controlled experimental
      study. SETTING: Research laboratory. CELLS: Mouse testis Sertoli cells (TM4).
      INTERVENTIONS: Sertoli cells were exposed to 0-200 MUg/mL plain media,
      unconjugated NPs, or FSH peptide-conjugated NPs for 2 or 24 hours to assess
      uptake. Next, Sertoli cells were exposed to 0-50 mmol H2O2 with 0-1 mg/mL
      unconjugated SOD-loaded NPs, FSH-conjugated SOD-loaded NPs, or equivalent units
      of SOD in solution as a control for 2-6 hours to assess influence on cell
      survival after oxidative stress. MAIN OUTCOME MEASURE(S): Cell viability, flow
      cytometry, and microscopy. RESULT(S): FSH peptide targeting improved uptake of
      NPs by Sertoli cells. FSH-conjugated SOD-NPs significantly protected Sertoli
      cells at 6 hours of H2O2--induced oxidative stress, with 100% survival with FSH
      conjugated SOD-NPs compared with unconjugated SOD-NPs (45%) or SOD in solution
      (36%). CONCLUSION(S): Conjugation of NPs with FSH peptide improves cellular
      uptake and survival when SOD-loaded NPs are coincubated with Sertoli cells
      undergoing oxidative stress. This study represents a step toward developing NPs
      for the targeted treatment of testicular oxidative stress.

PMID- 24290000
TI  - Decline of serum antimullerian hormone levels after laparoscopic ovarian
      cystectomy in endometrioma and other benign cysts: a prospective cohort study.
AB  - OBJECTIVE: To identify the most important factor in predicting ovarian reserve
      after laparoscopic ovarian cystectomy and to evaluate whether there is any
      difference in the postoperative decline of ovarian reserve between women with
      endometrioma and those with other benign ovarian cysts. DESIGN: Prospective
      cohort study. SETTING: University hospital. PATIENT(S): A total of 100 women who
      had undergone laparoscopic ovarian cystectomy for endometrioma (n = 68) or other
      benign ovarian cysts (n = 32). INTERVENTION(S): Serum antimullerian hormone (AMH)
      levels measured by enzyme immunoassay preoperatively and at 3 months after
      surgery. MAIN OUTCOME MEASURE(S): Rate of AMH decline after surgery and follicle
      numbers retained in cystectomy specimens. RESULT(S): Serum AMH levels were
      obviously decreased at 3 months after the surgery (4.97 +/- 2.83 vs. 3.33 +/-
      2.08 ng/mL, mean +/- standard deviation). Adjusting for several parameters, we
      could see that bilaterality of the ovarian cyst was the only significant factor
      in predicting the rate of postoperative decline of AMH levels. The rate of AMH
      decline did not differ between the endometrioma group and the other benign
      ovarian cyst group. CONCLUSION(S): Bilaterality of the ovarian cyst is the only
      significant factor in predicting the rate of decline of AMH level after
      laparoscopic ovarian cystectomy. The rate of decline of AMH levels after surgery
      was similar between the endometrioma group and the other benign ovarian cyst
      group.

PMID- 24290001
TI  - Controversy over the use of fresh versus frozen-thawed sperm for in vitro
      fertilization-intracytoplasmic sperm injection.

PMID- 24290002
TI  - High-intensity focused ultrasound for potential treatment of polycystic ovary
      syndrome: toward a noninvasive surgery.
AB  - OBJECTIVE: To investigate the feasibility of using high-intensity focused
      ultrasound (HIFU), under dual-mode ultrasound arrays (DMUAs) guidance, to induce
      localized thermal damage inside ovaries without damage to the ovarian surface.
      DESIGN: Laboratory feasibility study. SETTING: University-based laboratory.
      ANIMAL(S): Ex vivo canine and bovine ovaries. INTERVENTION(S): DMUA-guided HIFU.
      MAIN OUTCOME MEASURE(S): Detection of ovarian damage by ultrasound imaging, gross
      pathology, and histology. RESULT(S): It is feasible to induce localized thermal
      damage inside ovaries without damage to the ovarian surface. DMUA provided
      sensitive imaging feedback regarding the anatomy of the treated ovaries and the
      ablation process. Different ablation protocols were tested, and thermal damage
      within the treated ovaries was histologically characterized. CONCLUSION(S): The
      absence of damage to the ovarian surface may eliminate many of the complications
      linked to current laparoscopic ovarian drilling (LOD) techniques. HIFU may be
      used as a less traumatic tool to perform LOD.

PMID- 24290003
TI  - Effect of oxygen tensions on the proliferation and angiogenesis of endometriosis
      heterograft in severe combined immunodeficiency mice.
AB  - OBJECTIVE: To investigate the effects of oxygen on the proliferation and
      angiogenesis of endometriosis in vivo. DESIGN: Animal studies. SETTING: Animal
      research facility. ANIMAL(S): Thirty-six female severe combined immunodeficiency
      (SCID) mice, implanted with eutopic endometrium from seven endometriosis
      patients. INTERVENTION(S): Human eutopic endometrial tissues were randomized to
      normoxia, hyperoxia, or hypoxia pretreatment and were subcutaneously implanted
      into estrogen-treated ovariectomized SCID mice. MAIN OUTCOME MEASURE(S): The
      growth and quality of the implants were measured, and the expression of
      proliferation- and angiogenesis-associated markers (i.e., Ki67, CD31, vascular
      endothelial growth factor, and hypoxia-inducible factor-1alpha) were assessed
      using immunohistochemistry and Western blot analyses. RESULT(S): The growth
      curves of the implants were distinct with different oxygen pretreatments. The
      growth of the implants of the hypoxia group was significantly increased compared
      with the normoxia group, but the growth of the implants of the hyperoxia group
      was significantly decreased compared with the normoxia group. Microscopic
      examination indicated that lesions with hyperplastic cylindrical glandular
      epithelium were surrounded by the endometrial stroma in the hypoxia group, but
      the glandular epithelium was partially depauperate in the hyperoxia group. The
      expression of Ki67, CD31, vascular endothelial growth factor, and hypoxia
      inducible factor-1alpha in the hypoxia-pretreated implants was significantly
      higher compared with the hyperoxia or normoxia groups. CONCLUSION(S): Oxygen can
      alter the growth patterns of endometriosis implants in a SCID mouse model.
      Hypoxia pretreatment promoted the proliferation and angiogenesis of
      endometriosis, whereas hyperoxia pretreatment exhibited the opposite effect.

PMID- 24290004
TI  - An audit of the use of an opiate sparing, multimodal analgesic regime in children
      with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing
      adenotonsillectomy.
AB  - OBJECTIVES: Children with Sleep Disordered Breathing/Obstructive Sleep Apnoea
      have an increased incidence of respiratory complications following
      adenotonsillectomy. This may be partly related to an increase in sensitivity to
      opiates. An audit of such cases undergoing adenotonsillectomy was performed with
      the following aims: METHODS: All patients had Sleep Disordered
      Breathing/Obstructive Sleep Apnoea confirmed preoperatively by Overnight Oximetry
      Studies. Oximetry data was expressed as the lowest recorded saturation (SpO2 Low
      %) and number of significant desaturations (see text) per hour (ODI4%). Case
      notes and oximetry studies were scrutinized for relevant perioperative
      anaesthetic and analgesic data, risk factors and complications. RESULTS: The
      overall incidence of major and minor respiratory complications was low (1.6% and
      27% respectively). Children who suffered any complication were more likely to be
      younger (p=0.0078), have a lower SpO2 Low (p=0.004) and higher ODI4% (p=<0.0001).
      Multiple logistic regression showed ODI4% to be the best predictor of a potential
      respiratory complication (p=0.0032). An ODI4% of >8 may be the best cut off point
      in predicting complications (AUC=0.78, sensitivity=0.90) but it showed a poor
      specificity (0.57). Primary/secondary haemorrhage occurred in 0.4%/1.2%
      respectively and postoperative nausea and vomiting in 4.4%. CONCLUSIONS: A low
      dose opiate-based, multi modal analgesic regime appears to be effective and safe
      in children with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing
      adenotonsillectomy.

PMID- 24290005
TI  - Anesthesia mumps resulting in temporary facial nerve paralysis after the auditory
      brainstem implantation in a 3-year-old child.
AB  - An acute transient sialadenitis of the major salivary glands in the early
      postoperative period is called 'anesthesia mumps'. It has been reported in
      different surgical procedures especially in neurosurgical procedures. Anesthesia
      mumps develops very fast after the extubation period but it usually regresses
      with no sequelae within a few hours. However, sometimes serious complication can
      occur such as respiratory distress. In this report, we present a 3-year-old girl
      with an anesthesia mumps and facial palsy occurring after successful auditory
      brainstem implantation and we discuss the cause and the management of this rare
      complication in this report. 

PMID- 24290006
TI  - Empirical validation of Polish guidelines for the management of acute
      streptococcal pharyngitis in children.
AB  - OBJECTIVE: Group A Streptococcus (GAS) pharyngitis is currently the only commonly
      occurring form of acute pharyngitis for which antibiotic therapy is definitely
      indicated. Polish guidelines advocate the use of modified Centor score (MCS) to
      assess the probability of GAS pharyngitis. They advise performing throat culture
      or rapid antigen detection test (RADT) in children with score 2-3 in MCS and
      treating with antibiotic only those in whom GAS was detected. Negative RADT
      results should be confirmed by culture. In children with score 4, the guidelines
      allow to introduce empiric antibiotic therapy. Phenoxymethyl penicillin is
      recommended as a drug of choice to treat GAS pharyngitis. The aim of our study
      was to evaluate the accuracy of strategy recommended by Polish guidelines in
      identifying those children with acute pharyngitis who require antibiotic
      treatment. Hence, diagnostic values of score 4 in MCS and RADT were assessed
      using throat culture as a reference standard. Phenoxymethyl penicillin efficacy
      in GAS eradication and prevention of post-streptococcal complications were
      estimated as well. METHODS: Ninety children between 2 and 15 years of age with
      acute pharyngitis symptoms suggesting GAS etiology (MCS >= 2), participated in
      our study. At the initial visit MCS was evaluated and two throat swabs were
      collected to perform RADT and culture. In children with GAS pharyngitis treated
      with penicillin, microbiological cure was assessed by performing two control
      throat cultures. Next, children were under observation for 3 months. RESULTS:
      Positive predictive value of score 4 in MCS turned out to be 48.05% (95% CI: 36.5
      59.7%). RADT sensitivity, specificity and diagnostic accuracy proved to be 100%,
      96%, and 98%, respectively. GAS eradication rate in children treated with
      penicillin turned out to be 92.5%. No post-streptococcal sequelae occurred in any
      child in 3-month observation. CONCLUSIONS: Empiric antibiotic therapy in children
      with score 4 in MCS will result in significant overtreatment of those with
      nonstreptococcal pharyngitis. New generation RADT diagnostic value in GAS
      detection proved to be equivalent to that of culture, which obviates the need of
      backup culture in children with negative RADT results. Phenoxymethyl penicillin
      revealed high eradication efficacy and proved to prevent post-streptococcal
      sequelae in children with acute GAS pharyngitis.

PMID- 24290007
TI  - [Ethics in medical journals.]
AB  - The title of this reflection evokes several contents that may encompass from
      ethics in research; fraud in science; ethics in medical advertising and relations
      between sponsors and science; and, finally, papers related to ethic content. This
      paper is limited to the ethic responsibilities of the medical writers or
      "scriptwriters."

PMID- 24290008
TI  - [Levels of state-trait anxiety between mothers and fathers who have children in
      an intensive care unit.]
AB  - Background: when there is a child patient in the family, it is frequent that
      parents get upset. Anxiety in the mother and father could be different depending
      on the way each one lives the critical situation of the child patient. The
      purpose was to measure levels of anxiety in fathers and mothers who had a
      hospitalized child in an intensive care unit. Methods: the State-Trait Anxiety
      Inventory (STAI) was applied to a group of 50 pairs of parents who had a
      hospitalized child in the intensive care unit in a pediatric hospital. A no
      probabilistic intentional sample was used. Differences between groups were
      analyzed by Student's t test. Results: no significant differences were obtained
      between mothers and fathers for both state-anxiety and trait-anxiety. Significant
      differences were obtained intra-groups between both kinds of anxiety.
      Conclusions: having a child who is chronically sick or hospitalized for intensive
      therapy causes similar levels of anxiety in both parents. Anxiety is
      significantly increased in both parents when their child is hospitalized in an
      intensive therapy unit.

PMID- 24290009
TI  - [Hirschsprung's disease: the immunohistochemistry as ancillary method for the
      diagnosis.]
AB  - Background: the confirmatory diagnosis of Hirschsprung's disease is made by
      histopathological study. However, this procedure is limited with only hematoxylin
      and eosin staining, especially in biopsies of premature babies or when non-expert
      pathologists make the evaluation. The immunohistochemistry from ganglia cell
      calretinin has been used to reduce the risk of misdiagnosis. Our objective was to
      show the benefits of this antibody in diagnosis of Hirschsprung's disease in
      biopsy specimens. Methods: we evaluated patients with histopathological diagnosis
      of Hirschsprung's disease made by hematoxylin and eosin staining. We determined
      if there was enough paraffin block for immunohistochemistry with two markers:
      calretinin and neurofilaments. Three controls of autopsy of children under 3
      years of age with other diagnosis were included. Results: of a total of 48 cases
      with histopathological diagnosis of Hirschsprung's disease only 13 had adequate
      tissue for immunohistochemistry. The immunohistochemistry confirmed the diagnosis
      in nine cases. In the other four cases there were initial misdiagnosis due to
      evidence of calretinin (ganglion cells) and, thus, Hirschsprung's disease was
      discarded. Conclusions: the use of immunohistochemistry allows confirming the
      diagnosis of Hirschsprung's disease and reduce the risk of a false-positive
      result with only hematoxylin and eosin staining.

PMID- 24290010
TI  - [Learning styles in medical residents and their professors of a pediatric
      hospital.]
AB  - Background: the learning styles are cognitive, emotional, and psychological
      characteristics, which function as relatively stable indicators of how teachers
      and students perceive, interact, and respond to their learning environments.
      Knowing students' styles allows teachers to have tools to improve medical
      education. Our objective was to identify learning styles in pediatric residents
      and professors from a pediatric hospital. Methods: a learning styles
      questionnaire was applied to residents and theirs professors; data was analyzed
      in SPSS 12 software. Results: the dominant learning style in pediatric residents
      was reflexive and for professors was theoretical. There wasn't any difference
      between sexes or between medical or surgical specialities. There was more
      correlation between professors and residents when there was an increase in
      training time. Conclusions: the learning styles between professors and residents
      are different, especially at the beginning of the medical specialty courses;
      that's why it is necessary to realize a confrontation between the students'
      learning styles and teaching methods used by professors to improve significant
      learning. To know learning styles gives residents an important alternative to
      find a better study strategy.

PMID- 24290011
TI  - [Neonatal morbidity and hospital mortality of preterm triplets.]
AB  - Background: multiple gestations have caused an increase in vulnerable preterm
      births. Our objective was to analyze neonatal morbidity and mortality in preterm
      triplets. Methods: we analyzed a cohort of 30 triplets in an obstetrics and
      gynecology hospital. Data were obtained during pregnancy, childbirth and neonatal
      period: birth order, sex, weight, height, malformations, advanced resuscitation,
      assisted ventilation, intraventricular hemorrhage, necrotizing enterocolitis,
      sepsis, pulmonary hypertension, bronchopulmonary dysplasia, days of
      hospitalization, and death. Results: 90 infants were analyzed. There was an
      omphalopagus con-joined twins case; 42 (70 %) had between 30-33 weeks and six
      between 24-29; 19 (21 %) had low weight for gestational age, and 18 (30 %) had a
      major malformation; 27 % required ventilatory support, 33 % sepsis, 32 %
      necrotizing enterocolitis, 21 % pulmonary hypertension, 14 % bronchopulmonary
      dysplasia and 2 % intraventricular hemorrhage, without statistically significant
      differences related to the order, presentation at birth, sex and number of
      placentas and amniotic sacs. Eight 24-week triplets died, four over 28 weeks, and
      a siamese (p = 38). There was no difference in hospital days between triplets.
      Conclusions: the triplets mortality is low and mainly associated with extreme
      prematurity, intrauterine growth restriction and sepsis.

PMID- 24290012
TI  - [Risk factors associated to the epidemic outbreak of dengue virus infection.]
AB  - Objective: to identify the risk factors associated to the epidemic of dengue
      virus infections occurred at Queretaro, Mexico. Methods: a case-control study was
      carried out on 49 cases and 49 controls. The data included: age, sex, residency,
      schooling, occupation, clinical data, sources infected with Aedes aegypti,
      travelling, source of waters, and protection to water recipients. The protection
      to door and windows was investigated. chi2 test and odds ratio were estimated.
      Results: the age group of 20-39 years was the most affected and women
      predominated. The Satellite area contributed with 38 cases (77.1 %). The absence
      of mosquito nettings on windows had an OR = 1.8, and ignorance of preventive
      activities had an OR = 2.8, while the use of insecticides (OR = 0.30) and
      mosquito repellents (OR = 0.54) were protective factors. Conclusions: the
      epidemic outbreak in Queretaro confirmed that Aedes aegypti has adapted to
      greater heights. This fact should alert to the sanitary authorities to face the
      possibility of an epidemic outbreak with great affectation among population.

PMID- 24290013
TI  - [About the paper "Warning signs and symptoms on obstetric care..."]

PMID- 24290014
TI  - [Answer to comments about the paper "Warning signs and symptoms on obstetric
      care..."]

PMID- 24290015
TI  - [Hemophilia.]
AB  - Hemophilia is a genetic disease in which the clinical manifestation is mainly the
      presence of hemorrhage. There are two known types of hemophilia: hemophilia A and
      B, which have a deficiency of factor VIII or IX clotting, respectively. The
      intensity of bleeding in hemophilia depends on the plasma levels of factor VIII
      or IX and has traditionally been classified as mild (> 5 % activity), moderate (1
      5 % activity) and severe (< 1 % activity). In laboratory tests, isolated
      prolongation of activated partial thromboplastin time (aPTT) can be found, but it
      is necessary to determine the plasma levels of factor VIII or IX to establish the
      diagnosis of hemophilia A or B. The treating of this disease involves replacing
      exogenous factor VIII or IX concentrates. Gene therapy could be an option in the
      future to achieve the cure of the disease. Complications of hemophilia are the
      risk of transfusion-associated infections, pseudotumor hemophilic, hemophilic
      arthropathy and the presence of serum inhibitors.

PMID- 24290016
TI  - [Chromosomal instability in carcinogenesis of cervical cancer.]
AB  - In order to spot common chromosomal imbalances in early and late lesions of
      cervical cancer that might be used as progression biomarkers, we made a search of
      literature in PubMed from 1996 to 2011. The medical subject headings employed
      were chromosomal alterations, loss of heterozygosis, cervical cancer, cervical
      tumorigenesis, chromosomal aberrations, cervical intraepithelial neoplasm and low
      grade squamous intraepithelial lesion. The common chromosomal imbalances were
      gains in 8q24 (77.7 %), 20q13 (66.9 %), 3q26 (47.1 %), Xp22 (43.8 %), and 5p15
      (60 %), principally. On the other hand, integration of the high-risk human
      papillomavirus genome into the host chromosome has been associated with the
      development of neoplasia, but the chromosomal imbalances seem to precede and
      promote such integration. Chromosomal imbalances in 8q24, 20q13, 3q21-26 and 5p15
      Xp22, determined by fluorescent in situ hybridization assay or comparative
      genomic hybridization assay for early detection of the presence of high-risk
      human papillomavirus, are promising markers of cervical cancer progression.

PMID- 24290017
TI  - [Historical notes about scientific research in the Instituto Mexicano del Seguro
      Social.]
AB  - Medical research in the Instituto Mexicano del Seguro Social has been considered
      one of the most important in this country for quality and quantity. Thanks to the
      work and leadership of Benito Coquet, who initiated the building of the National
      Medical Center in 1961, and the work of two pillars of research, Luis Castelazo
      and Bernardo Sepulveda, the Institute successfully improved scientific research.
      In the years that followed, the Institute fostered the professionalization of
      research, the creation of research units in different areas of science, the
      incorporation of consolidated groups of researchers, the relationship with other
      institutions, the incorporation to the Sistema Nacional de Investigadores, the
      editing of a journal to expose outside the work done within the Institute, and
      the formation of a trust to raise funds for financing. Thanks to all that,
      institutional research strengthened in all lines, and it was placed first, at
      certain times, at the national level.

PMID- 24290018
TI  - [From clinical judgment to linear regression model.]
AB  - When we think about mathematical models, such as linear regression model, we
      think that these terms are only used by those engaged in research, a notion that
      is far from the truth. Legendre described the first mathematical model in 1805,
      and Galton introduced the formal term in 1886. Linear regression is one of the
      most commonly used regression models in clinical practice. It is useful to
      predict or show the relationship between two or more variables as long as the
      dependent variable is quantitative and has normal distribution. Stated in another
      way, the regression is used to predict a measure based on the knowledge of at
      least one other variable. Linear regression has as it's first objective to
      determine the slope or inclination of the regression line: Y = a + bx, where "a"
      is the intercept or regression constant and it is equivalent to "Y" value when
      "X" equals 0 and "b" (also called slope) indicates the increase or decrease that
      occurs when the variable "x" increases or decreases in one unit. In the
      regression line, "b" is called regression coefficient. The coefficient of
      determination (R2) indicates the importance of independent variables in the
      outcome.

PMID- 24290019
TI  - [Laparoscopic cholecystectomy with three-port and 25 millimeters long incision.]
AB  - Background: three-port and 25 mm total incision laparoscopic cholecystectomy has
      shown benefits compared to conventional laparoscopy. The aim was to examine the
      safety and feasibility of this technique. Methods: a three-port laparoscopic
      cholecystectomy trial was conducted through Cinvestav metasearcher, Seriunam and
      Rencis. The eligibility criteria were: three port laparoscopic cholecystectomy,
      25 mm total incision, and score = 17 on Data Review System. Trials which employed
      instruments smaller than 5 mm in diameter were excluded. The comparative
      variables were documented and results obtained in the selected trials were
      described. Results: four trials were selected, comprising 1767 cases (1329
      females and 438 males), average age was 44.3 years. Chronic cholecystitis was
      documented in 84.3 %, and acute cholecystitis in 14.7 %. Average surgical time
      was 54.5 minutes. An additional port was required in 4.8 % and 1.4 % was
      converted to open technique. Bile duct injury was presented in 0.11 %. The
      success rate was 94.9 %. Conclusions: three port and 25 mm total incision in
      laparoscopic cholecystectomy is safe and feasible.

PMID- 24290020
TI  - [Hemophilia camps.]
AB  - We reported the experience of hemophilia camps which was accomplished with
      patients from hospitals of the Instituto Mexicano del Seguro Social. The aim was
      to prepare the families and patients regarding the disease treatment, in order to
      promote the self sufficiency and to know the impact of the program on the course
      of the disease. Surveys were applied about treatment items and personal opinions
      were collected. The results of the national hemophilia camp were: group of 56
      patients, average 14 years, 2 % women, 51 % severe hemophilia and 43 % had
      hemophilic brothers. Benefits: patients increased their knowledge about earlier
      bleeding identification and the self-infusion method; they became aware on their
      responsibility in self care, timely treatment and duties at home. Hemophilia
      camps with patients are an option for attitude change before disease
      complications. Social network creation and the increase in self-sufficiency are
      other benefits.

PMID- 24290021
TI  - [Six-minute walk test in children with neuromuscular disease.]
AB  - Background: neuromuscular diseases affect the motor unit. When they evolve,
      respiratory complications are common; the six-minute walk test plays an important
      role in the assessment of functional capacity. Methods: prospective, transversal,
      descriptive and observational study. We studied seven children with a variety of
      neuromuscular diseases and spontaneous ambulation. We tested their lung function,
      and administered a six-minute walk test and a test of respiratory muscle strength
      to these children. Results: the age was 9.8 +/- 2.4 years. All patients were
      males. Forced vital capacity decreased in three patients (42.8 %), forced
      expiratory volume during the first second (2.04 +/- 1.4 L) and peak expiratory
      flow (4.33 +/- 3.3 L/s) were normal. The maximum strength of respiratory muscles
      was less than 60 % of predicted values. The distance covered in the six-minute
      walk test was lower when compared with healthy controls (29.9 %). Conclusions:
      the six-minute walk test can be a useful tool in early stages of this disease,
      since it is easy to perform and well tolerated by the patients.

PMID- 24290022
TI  - [Adverse events in patients from a pediatric hospital.]
AB  - Background: detection of adverse events is part of the safety management in
      hospitalized patients. The objective of this study was to describe the incidence
      of adverse events that occurred in a pediatric hospital. Methods: cross-sectional
      study of the adverse events occurred in a pediatric hospital from 2007 to 2009.
      Factors associated with their developmental causes were identified. The
      statistical analysis was descriptive and bivariate, with contingency tables to
      estimate the relationship between those factors. A p value = 0.05 was considered
      significant. Results: a total of 177 adverse events were registered. When they
      began, human factor occurred in 23 cases (13 %, OR = 1.41, p = 0.001),
      organizational factor was present in 71 cases (40 %, OR = 1.91, p = 0.236) and
      technical factor in 46 cases (26 %, OR = 0.87, p = 0.01). Blows or bruises from
      falls as a result of adverse events occurred in 71 cases (40 %, 95 % CI = 64-78).
      Conclusions: we found 1.84 events per 100 hospital discharges during the study
      period. The fall of patients ranked first of the adverse events identified.

PMID- 24290023
TI  - [Deep vein thrombosis prophylaxis.]
AB  - Background: despite the proven effectiveness of preventive therapy for deep vein
      thrombosis, a significant proportion of patients at risk for thromboembolism do
      not receive prophylaxis during hospitalization. Our objective was to determine
      the adherence to thrombosis prophylaxis guidelines in a general hospital as a
      quality control strategy. Methods: a random audit of clinical charts was
      conducted at the Tijuana General Hospital, Baja California, Mexico, to determine
      the degree of adherence to deep vein thrombosis prophylaxis guidelines. The
      instrument used was the Caprini's checklist for thrombosis risk assessment in
      adult patients. Results: the sample included 300 patient charts; 182 (60.7 %)
      were surgical patients and 118 were medical patients. Forty six patients (15.3 %)
      received deep vein thrombosis pharmacologic prophylaxis; 27.1 % of medical
      patients received deep vein thrombosis prophylaxis versus 8.3 % of surgical
      patients (p < 0.0001). Conclusions: our results show that adherence to DVT
      prophylaxis at our hospital is extremely low. Only 15.3 % of our patients at risk
      received treatment, and even patients with very high risk received treatment in
      less than 25 % of the cases. We have implemented strategies to increase
      compliance with clinical guidelines.

PMID- 24290024
TI  - [Use of collagen-polyvinylpirrolidone in the treatment of Parry-Romberg
      syndrome.]
AB  - Background: Parry-Romberg syndrome is characterized by the presence of
      progressive hemifacial atrophy that affects the growth and development of
      structures on one side of the face. Our objective was to introduce collagen
      polyvinylpirrolidone as a new therapeutic option for Parry-Romberg syndrome in
      two clinical cases. Clinical cases: two women, aging 56 and 28 years old, with
      facial hypocrhomic lesions, and right and left fronto-malar sunken area
      respectively, treated with topic steroids + penicilamina, fat grafts and silicone
      implants without improvement. We used collagen-polyvinylpirrolidone and they
      showed improvement: after six months there were not clinical or esthetical
      complications. Conclusions: collagen-polivinilpirrolidone could be a new
      therapeutic option for Parry-Romberg syndrome with good clinical and esthetical
      results. It is easy to apply and it has few side effects and without
      complications.

PMID- 24290025
TI  - [Merkel cell carcinoma experience in a reference medical center.]
AB  - Background: Merkel cell carcinoma is a rare tumor that occurs on areas exposed to
      ultraviolet light. It is usually asymptomatic and it is diagnosed late often. The
      treatment is surgical, associated with adjuvant radiotherapy. The objective was
      to present the experience in the management of Merkel cell carcinoma in a
      reference medical center. Methods: all patients with Merkel cell carcinoma
      treated at the Instituto de Investigaciones Medico-Biologicas of the Universidad
      Veracruzana during the period 2008 to 2011 were studied. Sex, age, evolution
      time, tumor localization, size, metastases and treatment were analyzed. Results:
      of 3217 patients treated, three cases were Merkel cell carcinoma (0.09 %), their
      age was 52.1 +/- 14.17, male predominance of 66.67 %; the evolution time was of
      29.66 +/- 35.36 months; the tumour localization was on inguinal region, anterior
      chest and left arm; the noodle size was of 6.0 +/- 5.19 cm; two patients had
      lymph node metastases. In two cases, resection and lymphadenectomy were
      performed. They all received radiation therapy and chemotherapy in one case.
      Histologically the medium variant predominated; immunohistochemistry was positive
      in the three cases. One patient died ten months after the study was done.
      Conclusions: our experience is similar with others authors, Merkel cell carcinoma
      is a rare tumor, usually diagnosed late, and it has poor survival.

PMID- 24290026
TI  - [Clinical practice guideline. Diagnosis and treatment of dyslipidemia.]
AB  - Non-communicable diseases are a public health problem in Mexico. Coronary heart
      disease and diabetes mellitus are the first and second cause of death in the
      country, followed by thrombotic cerebrovascular events. Cardiovascular diseases
      are the leading cause of death; one primary risk factor is hypercholesterolemia.
      The detection and treatment of lipid abnormalities is the key to the prevention
      and management of chronic non-communicable diseases. Two nationally
      representative surveys have shown that lipid abnormalities are the most common
      risk factors in Mexican adults. The purpose of this guide is to provide a basis
      for identifying dyslipidemia in a timely manner, and to systematize the criteria
      for diagnosis and treatment in the first and second level of care.

PMID- 24290027
TI  - Assessment of quadriceps muscle weakness in patients after total knee
      arthroplasty and total hip arthroplasty: methodological issues.
AB  - The aim of this exploratory study was to verify whether the evaluation of
      quadriceps muscle weakness is influenced by the testing modality (isometric vs.
      isokinetic vs. isoinertial) and by the calculation method (within-subject vs.
      between-subject comparisons) in patients 4-8months after total knee arthroplasty
      (TKA, n=29) and total hip arthroplasty (THA, n=30), and in healthy controls
      (n=19). Maximal quadriceps strength was evaluated as (1) the maximal voluntary
      contraction (MVC) torque during an isometric contraction, (2) the peak torque
      during an isokinetic contraction, and (3) the one repetition maximum (1-RM) load
      during an isoinertial contraction. Muscle weakness was calculated as the
      difference between the involved and the uninvolved side (within-subject
      comparison) and as the difference between the involved side of patients and
      controls (between-subject comparison). Muscle weakness estimates were not
      significantly affected by the calculation method (within-subject vs. between
      subject; P>0.05), whereas a significant main effect of testing modality (P<0.05)
      was observed. Isometric MVC torque provided smaller weakness estimates than
      isokinetic peak torque (P=0.06) and isoinertial 1-RM load (P=0.008), and the
      clinical occurrence of weakness (proportion of patients with large strength
      deficits) was also lower for MVC torque. These results have important
      implications for the evaluation of quadriceps muscle weakness in TKA and THA
      patients 4-8months after surgery. 

PMID- 24290028
TI  - [Post-splenectomy complications in primary immune thrombocytopenia. Literature
      review and preventive measures].
AB  - Management of primary immune thrombocytopenia (ITP) has changed, and clinical
      practice broadens the use of thrombopoietin receptor agonists and anti-CD20
      antibody as options for second-line therapy, as alternative to splenectomy.
      Splenectomy remains a successful, definitive curative treatment. The purpose of
      this review about the complications of the splenectomy, in the context of ITP, is
      to increase the awareness of clinicians towards the preventive measures, which
      are often not correctly applied.

PMID- 24290029
TI  - [Agranulocytosis and vasculitis in a cocaine addict: levamisole, the hidden
      culprit].
AB  - INTRODUCTION: Adulterants are compounds added to street drugs to increase profits
      for the seller. Levamisole, a veterinary antihelminthic agent, has become the
      most common adulterant of cocaine. The prevalence of levamisole in samples of
      cocaine is increasing. Levamisole can lead to neutropenia and to a dramatic
      vasculopathy and even vasculitis of small and medium-size blood vessels. CASE
      REPORT: We here reported the first French case of levamisole related toxicity,
      due to cocaine use in a 50-year-old man, revealed by fever and agranulocytosis,
      high titters of antineutrophil cytoplasmic antibodies (ANCA), anticoagulant and
      positive Coombs tests. Outcome was slowly favorable with exposition withdrawal.
      CONCLUSION: Clinicians should be aware that agranulocytosis or vasculitis or
      vasculopathy could be related to levamisole toxicity in individuals who use
      cocaine.

PMID- 24290030
TI  - [Neurological manifestations of Behcet's disease].
AB  - Neurological manifestations of Behcet's disease (BD) occur in 5.3 to more than
      50% of patients. They are divided into two major forms: "parenchymal" lesions,
      which include mainly meningoencephalitis as opposed to "extra-parenchymal"
      lesions (i.e. cerebral venous thrombosis and arterial aneurysms). Myelitis or
      peripheral neuropathy is exceptional. The neuro-Behcet syndrome (NBS) should be
      considered in the setting of neurological manifestations, particularly headache
      and pyramidal signs, in a young man diagnosed with BD. However, its recognition
      may be difficult when neurological manifestations are the presenting features of
      BD (one third of cases), and requires a thorough knowledge of clinical
      manifestations and morphological lesions. Thus, parenchymal NB lesions
      classically exhibit inflammatory characteristics on MRI and are located at the
      meso-diencephalic junction and in the brainstem, rarely with a supratentorial
      extension. Meningitis is not systematically associated, and may be absent in
      about 30% of cases. The pathogenesis of these lesions is incompletely understood,
      but inflammatory infiltrates include mainly neutrophils and activated T cells
      (mainly Th17). Differential diagnoses include infectious diseases (herpes,
      listeria, tuberculosis), and inflammatory diseases (i.e. multiple sclerosis and
      sarcoidosis). A prompt recognition of NBS should lead to initiate adequate
      therapies in order to limit the risk of sequelae, relapses or death. 

PMID- 24290032
TI  - Inflammation changes the expression of leukotriene receptors in porcine uteri.
AB  - Leukotrienes (LTs) are important as pro-inflammatory mediators to the innate
      immune response, inflammation, and allergy. Although it is known that
      inflammation of the uterus in gilts leads to an increase in LTB4 and LTC4
      synthesis, researchers lack knowledge regarding the expression of LT receptors in
      the inflamed uterus. The aim of this experiment was to determine the levels of
      cysteinyl LT receptors type 1 (CysLT(1)R) and type 2 (CysLT(2)R), as well as of
      LTB4 receptor type 1 (LTB4R1) mRNA and protein expression, and the cellular
      localization of these receptors in the inflamed porcine uterus. On Day 3 of the
      estrous cycle (Day 0 of the study), 50 ml of either saline or Escherichia coli
      suspension (109 colony-forming units/ml) was injected into each uterine horn.
      Injections of bacteria increased CysLT(1)R mRNA levels in the endometrium on Days
      8 and 16 of the study and in the myometrium on Day 16, as well as the CysLT(1)R
      protein level in the endometrium on Day 8. In the inflamed uteri, CysLT(2)R mRNA
      levels in the myometrium were increased on Days 8 and 16; however, the protein
      levels of this receptor decreased in the endometrium (Day 16) and myometrium (Day
      8). After bacterial treatment, LTB4R1 mRNA and protein levels in the endometrium
      on Day 8, and LTB4R1 mRNA levels in the myometrium on Days 8 and 16 were found to
      have increased. Data obtained show that inflammation of porcine uteri changes the
      expression of LT receptors, suggesting their importance in the
      course/consequences of uterine inflammation.

PMID- 24290031
TI  - Long noncoding RNAs: fresh perspectives into the RNA world.
AB  - Large-scale mapping of transcriptomes has revealed significant levels of
      transcriptional activity within both unannotated and annotated regions of the
      genome. Interestingly, many of the novel transcripts demonstrate tissue-specific
      expression and some level of sequence conservation across species, but most have
      low protein-coding potential. Here, we describe progress in identifying and
      characterizing long noncoding RNAs (lncRNAs) and review how these transcripts
      interact with other biological molecules to regulate diverse cellular processes.
      We also preview emerging techniques that will help advance the discovery and
      characterization of novel transcripts. Finally, we discuss the role of lncRNAs in
      disease and therapeutics. 

PMID- 24290033
TI  - Phenotypic characterisation of immune cell infiltrates in testicular germ cell
      neoplasia.
AB  - Immune cells often infiltrate testicular germ cell neoplasms, including pre
      invasive carcinoma in situ (CIS), but the significance of this phenomenon remains
      unknown. The composition and distribution of infiltrating immune cells were
      examined by immunohistochemistry in testis samples with CIS and overt seminoma,
      in comparison to biopsies from infertile men without neoplasia. The composition
      of immune cells was similar across all the groups studied. Macrophages, CD8+ and
      CD45R0+ T lymphocytes constituted the majority of infiltrates, B lymphocytes were
      present in an intermediate proportion and very few CD4+ and FoxP3+ T cells were
      detected. HLA-I antigen was more abundant in Sertoli cells in tubules containing
      CIS than in those with normal spermatogenesis. This study showed a phenotypically
      comparable composition of infiltrating immune cells independently of the presence
      of neoplasia, suggesting the absence of active immune surveillance in testicular
      germ cell cancer.

PMID- 24290034
TI  - The impact of oral cryotherapy and oral and gastrointestinal mucositis after
      autologous stem cell transplantation.

PMID- 24290035
TI  - Febrile neutropenia risk assessment tool: improving clinical outcomes for
      oncology patients.
AB  - PURPOSE: To develop, implement and evaluate the effectiveness of a nurse-led risk
      assessment tool to reduce the incidence of febrile neutropenia (FN) and evaluate
      the nurse's role in FN risk assessment in a hospital-based oncology unit. METHODS
      AND SAMPLE: A FN risk assessment tool was developed, implemented and evaluated. A
      comparative prospective observational chart review was undertaken to evaluate the
      tool. Clinical data were collected from 459 patients' records from August 2008
      through July 2009. Patients had no intervention during the first six months (n =
      233). Patients in the following six months (n = 226) had the FN risk assessment
      completed and appropriate granulocyte-colony stimulating factor prescribed. A
      self-questionnaire was utilised to evaluate the nurses' role in FN risk
      assessment. KEY RESULTS: The incidence of FN was reduced by 52% (p = 0.02).
      Hospital days, dose reductions and treatment delays were reduced. Nurses felt
      they were the most appropriate person to carry out the assessment. CONCLUSIONS:
      Through consistent risk assessment, nurses could determine which patients were at
      high risk of developing FN leading to significant reduction in life-threatening
      infections, hospitalisations, dose reductions and delays. Nurses can be confident
      and competent in decision-making to reduce life-threatening infections through
      the use of an FN risk assessment tool.

PMID- 24290036
TI  - To the Editor: Molecular epidemiology of toxigenic Clostridium difficile isolates
      in Korea.

PMID- 24290037
TI  - Depression screening in patients with coronary heart disease: does the evidence
      matter?

PMID- 24290038
TI  - A systematic review and meta-analysis of mindfulness-based stress reduction for
      the fibromyalgia syndrome.
AB  - OBJECTIVES: This paper presents a systematic review and meta-analysis of the
      effectiveness of mindfulness-based stress reduction (MBSR) for FMS. METHODS: The
      PubMed/MEDLINE, Cochrane Library, EMBASE, PsychINFO and CAMBASE databases were
      screened in September 2013 to identify randomized and non-randomized controlled
      trials comparing MBSR to control interventions. Major outcome measures were
      quality of life and pain; secondary outcomes included sleep quality, fatigue,
      depression and safety. Standardized mean differences and 95% confidence intervals
      were calculated. RESULTS: Six trials were located with a total of 674 FMS
      patients. Analyses revealed low quality evidence for short-term improvement of
      quality of life (SMD=-0.35; 95% CI -0.57 to -0.12; P=0.002) and pain (SMD=-0.23;
      95% CI -0.46 to -0.01; P=0.04) after MBSR, when compared to usual care; and for
      short-term improvement of quality of life (SMD=-0.32; 95% CI -0.59 to -0.04;
      P=0.02) and pain (SMD=-0.44; 95% CI -0.73 to -0.16; P=0.002) after MBSR, when
      compared to active control interventions. Effects were not robust against bias.
      No evidence was further found for secondary outcomes or long-term effects of
      MBSR. Safety data were not reported in any trial. CONCLUSIONS: This systematic
      review found that MBSR might be a useful approach for FMS patients. According to
      the quality of evidence only a weak recommendation for MBSR can be made at this
      point. Further high quality RCTs are required for a conclusive judgment of its
      effects.

PMID- 24290040
TI  - Depression, not anxiety, is independently associated with 5-year hospitalizations
      and mortality in patients with ischemic heart disease.
AB  - OBJECTIVE: The objective of the current study was to examine whether depression
      and anxiety are independently associated with 5-year cardiac-related
      hospitalizations and all-cause mortality in patients with ischemic heart disease
      (IHD). METHODS: Patients treated for MI, angina, or ischemic heart failure
      (N=610) were recruited from Holbaek Hospital, Denmark. All patients completed the
      Hospital Anxiety and Depression Scale (HADS) in December 2005. Data regarding
      patient characteristics at baseline, and hospitalizations and deaths during
      follow-up were collected from Danish population-based registers. Cox and negative
      binomial regression analyses were performed to examine the relationship between
      depression, anxiety and the endpoints. RESULTS: At baseline, 71 (11.6%) patients
      reported depression and 120 (19.7%) reported anxiety. Models including both
      depression and anxiety showed that depression was independently associated with
      time to first cardiac-related hospitalization, cumulative number and length of
      cardiac-related hospitalizations, and all-cause mortality, while anxiety was only
      associated with the total length of hospitalizations (all p-values <.05). After
      adding sociodemographic and clinical factors, depression remained associated with
      the number (incidence rate ratio (IRR)=2.00, 95% confidence interval (CI): 1.44
      2.77) and length of cardiac-related hospitalizations (IRR=3.69, 95% CI: 2.75
      4.96), and all-cause mortality (hazard ratio (HR)=2.12, 95% CI: 1.13-3.96). The
      associations between depression and time to first hospitalization and between
      anxiety and length of stay were eliminated. CONCLUSIONS: The current study showed
      that depression, and not anxiety, is associated with the number and length of
      cardiac-related hospitalizations and all-cause mortality in IHD patients,
      independent of traditional risk factors. In order to improve health outcomes,
      better awareness and treatment of depression in IHD patients are crucial.

PMID- 24290039
TI  - Depression, anxiety, and prevalent diabetes in the Chinese population: findings
      from the China Kadoorie Biobank of 0.5 million people.
AB  - OBJECTIVE: Despite previous investigation, uncertainty remains about the nature
      of the associations of major depression (MD) with type 2 diabetes mellitus
      (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety
      disorder (GAD) for T2DM. METHODS: Cross-sectional data from the China Kadoorie
      Biobank Study, a sample of approximately 500,000 adults from 10 geographically
      defined regions of China, were analyzed. Past year MD and GAD were assessed using
      the Composite International Diagnostic Inventory. T2DM was defined as either
      having self-reported physician diagnosis of diabetes at age 30 or later
      ("clinically-identified" cases) or having a non-fasting blood glucose>=11.1mmol/L
      or fasting blood glucose>=7.0mmol/L but no prior diagnosis of diabetes ("screen
      detected" cases). Logistic regression was used to assess the relationship between
      MD and GAD with clinically-identified and screen-detected T2DM, adjusting for
      demographic characteristics and health behaviors. RESULTS: The prevalence of T2DM
      was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was
      significantly associated with clinically-identified T2DM (odds ratio [OR]: 1.75,
      95% confidence interval (CI): 1.47-2.08), but not with screen-detected T2DM (OR:
      1.18, 95% CI: 0.92-1.51). GAD was associated with clinically-identified (OR:
      2.14, 95% CI: 1.60-2.88) and modestly associated with screen-detected (OR: 1.44,
      95% CI: 0.99-2.08) T2DM. The relationship between MD and GAD with T2DM was
      moderated by obesity. CONCLUSION: MD is associated with clinically-identified,
      but not screen-detected T2DM. GAD is associated with both clinically-identified
      and screen-detected T2DM. The relationship between MD and T2DM is strongest among
      those who are not obese.

PMID- 24290041
TI  - Assessing Bodily Preoccupations is sufficient: clinically effective screening for
      hypochondriasis.
AB  - OBJECTIVE: Hypochondriasis is a persistent psychiatric disorder and is associated
      with increased utilisation of health care services. However, effective
      psychiatric consultation interventions and CBT treatments are available. In the
      present study, we provide evidence of clinically effective screening for
      hypochondriasis. We describe the clinically effective identification of patients
      with a high probability of suffering from hypochondriasis. This identification is
      achieved by means of two brief standardised screening instruments, namely the
      Bodily Preoccupation (BP) Scale with 3 items and the Whiteley-7 (WI-7) with 7
      items. METHODS: Both the BP scale and the WI-7 were examined in a sample of 228
      participants (72 with hypochondriasis, 80 with anxiety disorders and 76 healthy
      controls) in a large psychotherapy outpatients' unit, applying the DSM-IV
      criteria. Cut-off values for the BP scale and the WI-7 were computed to identify
      patients with a high probability of suffering from hypochondriasis. Additionally,
      other self-report symptom severity scales were completed in order to examine
      discriminant and convergent validity. Data was collected from June 2010 to March
      2013. RESULTS: The BP scale and the WI-7 discriminated significantly between
      patients with hypochondriasis and those with an anxiety disorder (d=2.42 and
      d=2.34). Cut-off values for these two screening scales could be provided, thus
      identifying patients with a high probability of suffering from hypochondriasis.
      CONCLUSIONS: In order to reduce costs, the BP scale or the WI-7 should be applied
      in medical or primary care settings, to screen for patients with a high
      probability of hypochondriasis and to transfer them to further assessment and
      effective treatment.

PMID- 24290042
TI  - Longitudinal course of insomnia: age-related differences in subjective sleepiness
      and vigilance performance in a population-based sample.
AB  - OBJECTIVE: The present study utilized a population-based sample investigating the
      following aims: (1) compare the longitudinal course of insomnia in middle-aged
      and older adults and (2) examine age-related differences on subjective complaint
      and objective performance in middle-aged and older adults based on the course of
      insomnia. METHODS: 1657 middle-aged adults (48.16% male, mean age=55.35+/
      4.03years) and 405 older adults (48.40% male, mean age=70.13+/-3.88years) from
      the Korean Genome and Epidemiology Study (KoGES) were classified into 4 groups -
      no insomnia (NI), single episode insomnia (SEI), remitted persistent insomnia (PI
      R), and ongoing persistent insomnia (PI-O) based on their course of insomnia over
      5 time points spaced two years apart. Their performance on the psychomotor
      vigilance task (PVT) and subjective daytime sleepiness were compared across
      different insomnia groups, and the results were compared between middle-aged
      adults and older adults. RESULTS: Analysis of covariance indicated that
      subjective daytime sleepiness was significantly different across the insomnia
      groups in middle-aged adults based on insomnia group (P=<.0001), but, did not
      affect objective vigilance performance. In contrast, older adults displayed
      significantly different PVT response time, but not daytime sleepiness, based on
      insomnia group (P=0.03). CONCLUSION: Insomnia impacts psychomotor performance and
      subjective sleepiness differently, based on age group. There may be underlying
      processes associated with the aging that amplifies the impact of insomnia on
      vigilance performance, yet lessens perceived sleepiness in older adults.

PMID- 24290043
TI  - Sleep and psychological health during early recovery from critical illness: an
      observational study.
AB  - INTRODUCTION: Intensive care patients often report sleep disruption in ICU and
      during recovery from critical illness. OBJECTIVES: To assess: (i) patients' self
      reported sleep quality in ICU, on the hospital ward after transfer from ICU and
      two and six months after hospital discharge; (ii) whether patients who report
      sleep disruption in ICU continue to report sleep disruption in recovery and (iii)
      whether prehospital insomnia, experiences in intensive care, quality of life and
      psychological health are associated with sleep disruption six months after
      hospital discharge. METHODS: Patients completed self-report measures on sleep
      quality at five time points: prior to hospitalization, in ICU, the hospital ward,
      two months and six months after hospital discharge, their intensive care
      experiences two months after discharge and psychological health and quality of
      life six months after discharge. RESULTS: Patients (n=222) were aged (mean+/-SD)
      57.2+/-17.2years, 35% female, had mean ICU stay of 5+/-6days and BMI of 26+/-5.
      Over half the participants (57%) reported poor sleep at six months; for 10% this
      was at all time points after ICU admission. Prehospitalization insomnia
      (p=.0005), sleep quality on the ward (p=.006), anxiety (p=.002), and mental
      (p=.0005) and physical health (p=.0005) were independently associated with poorer
      sleep quality in survivors six months after ICU treatment. CONCLUSIONS: Sleep is
      a significant issue for more than half of survivors 6months after ICU treatment.
      Some influencing factors, such as hospital sleep quality, anxiety, physical
      health and mental health, are potentially modifiable and should be targeted in
      recovery programs.

PMID- 24290044
TI  - Longitudinal relationships of insomnia, nightmares, and PTSD severity in recent
      combat veterans.
AB  - OBJECTIVE: This observational, longitudinal study of veterans with recent combat
      exposure describes the prevalence, severity and associations of posttraumatic
      stress disorder (PTSD), insomnia, and nightmares over time. METHODS: Eighty
      recent combat veterans recruited from Veterans Health Administration primary care
      settings met inclusion criteria including hazardous alcohol use and at least
      subthreshold PTSD. Insomnia status and nightmare status were assigned based on
      the Insomnia Severity Index total score and the PTSD Checklist nightmare item,
      respectively. Participants were re-assessed six months following their baseline
      assessment. Analyses of variance compared insomnia and nightmare groups on PTSD,
      depression, and alcohol use severity. Analyses of covariance (controlling for
      baseline differences) examined whether insomnia and/or nightmares were associated
      with the clinical course of PTSD. Persistence of conditions was also examined.
      RESULTS: At baseline, 74% presented with insomnia and 61% endorsed distressing
      nightmares. Insomnia was associated with significantly higher PTSD and depression
      severity at both baseline and six months. The presence of nightmares was
      associated with significantly higher PTSD severity at both time points and with
      depression severity at baseline only. Despite decreases in PTSD and depression
      severity, insomnia severity was relatively unchanged after six months. The
      prevalence and severity of nightmare complaints diminished modestly over time.
      CONCLUSION: Among this sample of recent combat veterans, insomnia and nightmares
      were each strongly associated with the severity of both PTSD and depressive
      symptoms. Over time, insomnia in particular did not appear to resolve
      spontaneously and was associated with ongoing PTSD. Addressing insomnia early,
      therefore, may be a strategy to alter the course of PTSD.

PMID- 24290045
TI  - Relationships between sleep disturbances and gastroesophageal reflux disease in
      Asian sleep clinic referrals.
AB  - OBJECTIVE: Studies on the association between gastroesophageal reflux disease
      (GERD) and sleep apnea syndrome (SAS) have reported conflicting results, and
      attention has not been paid to the relationship between GERD and other sleep
      disorders. The aim of the study was to evaluate the relationship between GERD and
      various aspects of sleep disturbances. METHODS: A total of 564 subjects who were
      referred to a sleep laboratory were enrolled in the study. They underwent
      nocturnal polysomnography (NPSG), and they were asked to complete a GERD
      questionnaire. The questionnaire consisted of 14 items, and included questions on
      seven reflux symptoms, namely, heartburn, acid regurgitation, chest pain,
      hoarseness, globus sensation, coughing and epigastric soreness. Subjects
      reporting heartburn or acid regurgitation at least once a week were classified as
      having GERD. RESULTS: Among 564 participants, 51 subjects (9.0%) were diagnosed
      as having GERD. GERD patients had higher scores in Beck depression inventory
      (p<.01), Epworth sleepiness scale (p=.03), Pittsburg sleep quality index (p<.01),
      more spontaneous arousals in NPSG, and more alcohol consumption than non-GERD
      patients. There was no association between presence of GERD, SAS-related
      variables, and body mass index (BMI). GERD was significantly associated with poor
      sleep quality (adjusted OR, 3.5; 95% CI, 1.3-9.3) and depressed mood (adjusted
      OR, 2.8; 95% CI, 1.5-5.3). CONCLUSION: Poor subjective sleep and depressive
      symptoms are associated with the presence of GERD with no association between
      SAS, BMI and GERD. In managing patients with GERD, psychiatric and sleep symptoms
      need to be evaluated and appropriately treated.

PMID- 24290046
TI  - Psychometric evaluation of the revised Illness Perception Questionnaire (IPQ-R)
      in cancer patients: confirmatory factor analysis and Rasch analysis.
AB  - OBJECTIVE: To provide new insights into the psychometrics of the revised Illness
      Perception Questionnaire (IPQ-R) in cancer patients. To undertake, for the first
      time using data from breast, colorectal and prostate cancer patients, a
      confirmatory factor analysis (CFA) to assess the validity of the IPQ-R's core
      seven-factor structure. Also, for the first time in any illness group, to
      undertake Rasch analysis to explore the extent to which the IPQ-R factors form
      unidimensional scales, with linear measurement properties and no Differential
      Item Functioning (DIF). METHODS: Patients with potentially curable breast,
      colorectal or prostate cancer, within 6months post-diagnosis, completed the IPQ-R
      online (N=531). CFA was conducted, including multi-sample analysis, and for each
      IPQ-R factor fit to the Rasch model was assessed by examining, amongst other
      things, item fit, DIF and unidimensionality. RESULTS: The CFA showed a moderate
      fit of the data to the IPQ-R model, and stability across diagnosis, although fit
      was significantly improved following the removal of selected items. All seven
      factors achieved fit to the Rasch model, and exhibited unidimensionality and
      minimal DIF, although in most cases this was after some item rescoring and/or
      deletion. In both analyses, IPQ-R items 12, 18 and 24 were indicated as
      misfitting and removed. CONCLUSION: Given the rigorous standard of Rasch
      measurement, and the generic nature of the IPQ-R, it stood up well to the demands
      of the Rasch model in this study. Importantly, the results show that with some
      relatively minor, pragmatic modifications the IPQ-R could possess Rasch-standard
      measurement in cancer patients.

PMID- 24290047
TI  - Development and validity of the Patient-centred COPD Questionnaire (PCQ).
AB  - OBJECTIVE: COPD-guidelines recommend regular evaluation of both the degree of
      airway obstruction and health-status to provide adequate treatment. Numerous
      health-status questionnaires have been developed of which the 'Clinical-COPD
      Questionnaire' and the 'COPD-Assessment-Test' are best known; although highly
      recommended, both have several limitations regarding structure, content, and/or
      methodological qualities. In the present study a new COPD-specific instrument was
      developed to measure impairment: the 'Patient-centred-COPD-Questionnaire' (PCQ).
      METHODS: Six focus groups with COPD patients and (lung) health care providers
      from primary, secondary and tertiary (rehabilitation) care were formed to discuss
      aspects of COPD most relevant to patients' daily lives. Eighty candidate items
      were derived for explorative factor analyses (EFA) to test their psychometric
      properties (study I, n=541). These resulted in an 18-item scale that was further
      explored by confirmatory factor analyses (CFA) and construct and concurrent
      validity assessment (study II, n=412). RESULTS: EFA in study I suggested a
      reliable three component solution ('shortness of breath', 'acceptance of COPD'
      and 'confidence in care'). In study II this model was confirmed with CFA, and
      significant and clinically relevant correlations were found between the PCQ
      subscales, and other COPD specific and general health questionnaires.
      Furthermore, multivariate analyses of covariance revealed that more severely ill
      patients reported more impairment. CONCLUSIONS: The PCQ is a questionnaire with
      three dimensions to assess the impact of COPD on daily life that is easy to
      complete. For the first time, a dimension referring to 'confidence in care' is
      included in a tool that assesses COPD-related impairment.

PMID- 24290048
TI  - Effect of Type D personality on medication adherence in early adolescents with
      asthma.
AB  - OBJECTIVE: Medication adherence for daily preventive asthma medication is
      especially low during adolescence. In the present study, we aimed to test whether
      Type D personality (both as a category and with its constituent components
      (negative affectivity: NA and social inhibition: SI) separately and in
      interaction) predicts medication adherence of early adolescents with asthma.
      METHODS: In a prospective study, 188 early adolescents with asthma who were
      prescribed daily preventive asthma medication completed questionnaires on Type D
      personality, medication adherence, socio-demographic and clinical information,
      and depressive symptoms in the Spring/Summer of 2011 (T1) and again 12months
      later (T2). Multiple regression analyses, controlling for demographic and
      clinical information and for depressive symptoms, were conducted to test whether
      Type D personality (either as a categorical or dimensional construct) predicted
      changes in medication adherence over time. RESULTS: Adherence was significantly
      lower at T2 than at T1 and this decrease was predicted by the categorical
      construct of Type D personality. Analyses of the two separate dimensions NA and
      SI and their interaction showed that higher scores on NA at T1 predicted more
      decrease in adherence over time. Neither SI nor the interaction between NA and SI
      predicted changes in adherence. CONCLUSION: This is the first study to test the
      relationship between Type D personality and medication adherence in adolescents.
      Although categorical Type D personality predicts mediation adherence of
      adolescent with asthma over time, dimensional analyses suggest that this is due
      to negative affectivity only, and not to the combination of negative affectivity
      and social inhibition.

PMID- 24290049
TI  - Serotonin transporter availability in the midbrain and perceived social support
      in healthy volunteers.
AB  - OBJECTIVE: Serotonin modulates human behavior and emotion. Recent evidence
      implies that a higher level of serotonergic activity could be associated with a
      higher level of perceived social support. This study aimed to examine the
      correlation between serotonin transporter (SERT) availability and perceived
      social support scores in healthy volunteers. METHODS: 111 healthy participants,
      50 males and 61 females, were enrolled from the community and completed the
      Measurement of Support Function questionnaire. Single photon emission computed
      tomography (SPECT) with [(123)I] ADAM was performed to examine SERT availability.
      RESULTS: Perceived social support was positively correlated with SERT
      availability (Spearman's rho=0.29, p<0.01; chi(2)=7.57, p<0.01), particularly in
      males (Spearman's rho=0.37, p<0 .01; chi(2)=11.77, p<0.01). Censored regressions
      indicated that these associations are not influenced by a ceiling effect and
      remained significant after controlling the effect of age. CONCLUSIONS: This
      result confirmed the correlation between perceived social support and central
      serotonergic activity. However, this correlation was present only in males.

PMID- 24290050
TI  - First annual scientific meeting of the EAPM Cambridge 2013: conference report.

PMID- 24290051
TI  - A commentary on: Somatic Symptom Disorder: an important change in DSM.

PMID- 24290052
TI  - Tradeoffs between validity and utility in the diagnosis of Somatic Symptom
      Disorder.

PMID- 24290053
TI  - The Somatic Symptom Disorder in DSM 5 risks mislabelling people with major
      medical diseases as mentally ill.

PMID- 24290054
TI  - Diagnosis of Somatic Symptom Disorder requires clinical judgment.

PMID- 24290055
TI  - Differentiating pericardial recesses from mediastinal adenopathy: potential
      pitfalls in oncological imaging.
AB  - In oncological imaging, staging with computed tomography (CT) is widely used to
      determine treatment. Misinterpretation of fluid in pericardial recesses as
      mediastinal adenopathy can lead to inaccurate clinical staging and inappropriate
      management. In this review, we describe normal pericardial anatomy and illustrate
      imaging features to differentiate fluid in pericardial sinuses and recesses from
      mediastinal adenopathy. 

PMID- 24290056
TI  - Using an alternate light source to detect electrically singed feathers and hair
      in a forensic setting.
AB  - Mortality due to electrical injury in wildlife may occur in the form of lightning
      strike or power line contact. Evidence of electrical contact may be grossly
      obvious, with extensive singeing, curling, and blackening of feathers, fur, or
      skin. Occasionally, changes may be subtle, owing to lower current or reduced
      conductivity, making a definitive diagnosis of electrocution more difficult. We
      describe the use of an alternate light source in the examination of cases of
      lightning strike and power line contact in wildlife, and the enhanced detection
      of changes due to electrical currents in the hair and feathers of affected
      animals. Subtle changes in the wing feathers of 12 snow geese and 1 wolf that
      were struck by separate lightning events were made obvious by the use of an
      alternate light source. Similarly, this technique can be used to strengthen the
      evidence for power line exposure in birds. 

PMID- 24290057
TI  - Ultrasonic degradation of N-di and trihydroxy benzoyl chitosans and its effects
      on antioxidant activity.
AB  - Modified chitosans with 3,4-dihydroxy benzoyl groups (CS-DHBA) and 3,4,5
      trihydroxy benzoyl groups (CS-THBA) were synthesized and their chemical
      structures were determined by Fourier transform infrared (FT-IR) and (1)H nuclear
      magnetic resonance ((1)H NMR) spectroscopy. Then, ultrasonic degradation of CS,
      CS-DHBA and CS-THBA in 1% acetic acid solution was investigated. The kinetics
      studies of degradation were followed by gel permeation chromatography (GPC). The
      results indicated that the weight-average molecular weight of chitosan decreased
      obviously after ultrasound treatment, but molecular weights of CS-DHBA and CS
      THBA decreased slowly with increasing sonication time. Degradation kinetics model
      based on 1/Mt-1/M0=kt was used to estimate the degradation rate constant. It was
      found that the rates of degradation of CS-DHBA and CS-THBA are lower than CS, and
      follow the order: CS4>CS8>CS12>CS-THBA4>CS-THBA8 ~ CS-DHBA4>CS-THBA12>CS-DHBA8>CS
      DHBA12. The antioxidant activity of the CS, CS-DHBA and CS-THBA before and after
      sonication was investigated by the radical scavenging activity method using 1,1
      diphenyl-2-picrylhydrazyl (DPPH). The DPPH scavenging free radical capacity of CS
      THBA and CS-DHBA increased up to 89% and 74% respectively, when the concentration
      reached 6 MUg/ml. The ultrasonic treatment of CS-DHBA and CS-THBA after 30 min
      decreased the DPPH free radical scavenging activity but ultrasonic treatment of
      CS increased the DPPH free radical scavenging activity.

PMID- 24290058
TI  - Expression of New York esophageal squamous cell carcinoma-1 in primary and
      metastatic melanoma.
AB  - New York esophageal squamous cell carcinoma-1 (NY-ESO-1), a cancer testis
      antigen, is an ideal target for adoptive cell transfer immunotherapy. Evidence
      from several clinical trials in melanoma and other malignancies shows the
      potential value of targeting the NY-ESO-1 antigen in immune-based therapy of
      metastatic tumors. However, the incidence of NY-ESO-1 expression in metastatic
      melanoma is unknown, and thus, it is unclear how many patients might benefit from
      this therapy. In this study, we analyzed NY-ESO-1 expression in 222 melanoma
      specimens, including 16 primary and 206 metastatic tumors. Our results support
      previous findings showing higher expression of NY-ESO-1 in metastatic (58/206;
      28.2%) versus primary (0/16) tumors. In addition, our results show that the
      epithelioid subtype of melanoma has the highest incidence of NY-ESO-1 expression.
      These findings provide evidence of the value of this specific adoptive cell
      transfer therapy for the treatment of metastatic melanoma. 

PMID- 24290059
TI  - Predictors of unknown HIV serostatus at the time of labor and delivery in
      Kampala, Uganda.
AB  - OBJECTIVE: To determine factors associated with an unknown HIV serostatus among
      pregnant women admitted in labor to Mulago Hospital, Kampala, Uganda. METHODS: In
      total, 665 pregnant women admitted to Mulago Hospital were interviewed about
      their sociodemographic characteristics, obstetric history, access to prenatal
      care, fears regarding HIV testing, and knowledge about modes of mother-to-child
      transmission (MTCT). Knowledge of the HIV serostatus was assessed by self-report
      and verified by prenatal card review. RESULTS: The prevalence of unknown HIV
      serostatus at the time of labor was 27.1%. Factors associated with an unknown HIV
      serostatus included high parity (odds ratio [OR] 1.9; 95% confidence interval
      [CI], 1.16-3.14), preterm delivery (OR 2.60; 95% CI, 1.06-6.34), prenatal care at
      a private clinic (OR 12.87; 95% CI, 5.68-29.14), residence more than 5 km from
      the nearest prenatal clinic (OR 2.86; 95% CI, 1.18-17.9), high knowledge about
      MTCT (OR 0.25; 95% CI, 0.07-0.86), and fears related to disclosing the test
      result to the partner (OR 3.60; 95% CI, 1.84-7.06). CONCLUSION: The high
      prevalence of unknown HIV serostatus among women in labor highlights the need to
      improve accessibility to HIV testing services early during pregnancy to be able
      to take advantage of antiretroviral therapy.

PMID- 24290060
TI  - Activity of linezolid-containing regimens against multidrug-resistant
      tuberculosis in mice.
AB  - The objective of the present study was to compare the activities of regimens
      containing linezolid (LZD) with those not containing LZD against Mycobacterium
      tuberculosis infection in mice. The three regimens excluding LZD selected in this
      study are often used in practice against multidrug-resistant tuberculosis (MDR
      TB). When LZD was added to these MDR-TB regimens, the combinations were
      significantly more active after 2 months of therapy with regard to lung CFU
      reductions. The activity of LZD-containing regimens was greater than the World
      Health Organization's standard first-line regimen of
      rifampicin+isoniazid+pyrazinamide. In particular, when LZD was included in the
      combination levofloxacin+amikacin+para-aminosalicylic
      acid+pyrazinamide+clofazimine, culture negativity of the lungs was reached after
      2 months of treatment in every case. In addition, the serum levels of interleukin
      10 and interferon-gamma of mice were determined and were found not to be
      surrogate markers of bacterial clearance. 

PMID- 24290061
TI  - Dammarane triterpenes from the leaves of Panax ginseng enhance cellular immunity.
AB  - In our search for immune stimulating materials from natural source, bioassay
      guided fractionation of a methanol extract of Panax ginseng leaves led to the
      isolation of three dammarane triterpenes (1-3), including two previously unknown
      compounds 27-demethyl-(E,E)-20(22),23-dien-3beta,6alpha,12beta-trihydroxydammar
      25-one (1) and 3beta,20(S)-dihydroxydammar-24-en-12beta,23beta-epoxy-20-O-beta-D
      glucopyranoside (2). Their structures were elucidated on the basis of
      spectroscopic methods, chemical transformation, and by the comparison with those
      of literature data. Compounds 1-3 significantly increased interleukin-12
      expression in LPS-activated mouse peritoneal macrophage at a concentration of 100
      ng/mL. Furthermore, compound 1 strongly increased the Th1 response-mediated
      cytokine IL-2, and decreased Th2 response-mediated cytokines IL-4 and IL-6
      expression at 100 ng/mL on ConA-activated splenocytes. This study indicated that
      compound 1 showed a better effect on cellular immunity, and provided new chemical
      entities as promising lead compounds for the treatment of cellular immunity
      related diseases.

PMID- 24290063
TI  - From NMDA receptor antagonists to discovery of selective sigma2 receptor ligands.
AB  - Following previous studies focused on the search for new molecules targeting
      GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin
      1-yl)ethanone derivatives has been synthesized by using Microwave Assisted
      Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target
      effects we also tested their affinity towards sigma receptors. Binding assay
      revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1
      yl)ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a
      and 6a were efficient and selective ligands toward sigma2 receptor (Ki values of
      10nM and 20 nM, respectively). Thus, in this case the discovery of new sigma2
      receptor selective ligands was an unexpected result emerging from the screening
      of cross-activity against other CNS receptors.

PMID- 24290062
TI  - Small molecule inhibitors of anthrax lethal factor toxin.
AB  - This manuscript describes the preparation of new small molecule inhibitors of
      Bacillus anthracis lethal factor. Our starting point was the symmetrical, bis
      quinolinyl compound 1 (NSC 12155). Optimization of one half of this molecule led
      to new LF inhibitors that were desymmetrized to afford more drug-like compounds. 

PMID- 24290064
TI  - Synthesis and pharmacological characterization of 1-benzyl-4-aminoindole-based
      thyroid hormone receptor beta agonists.
AB  - A series of 1-benzylindole-based TRbeta agonists were prepared and evaluated.
      Compounds 11b' and 11c' were found to have cholesterol-lowering in a rat model
      with marginal effects on cardiac function and HPT axis. The present work
      illustrates the potential use of indoles as inner ring isosteres. 

PMID- 24290066
TI  - Traumatic bile duct neuroma developing in a remnant choledochal cyst.

PMID- 24290065
TI  - Modeling in vitro inhibition of butyrylcholinesterase using molecular docking,
      multi-linear regression and artificial neural network approaches.
AB  - Butyrylcholinesterase (BChE) has been an important protein used for development
      of anti-cocaine medication. Through computational design, BChE mutants with ~2000
      fold improved catalytic efficiency against cocaine have been discovered in our
      lab. To study drug-enzyme interaction it is important to build mathematical model
      to predict molecular inhibitory activity against BChE. This report presents a
      neural network (NN) QSAR study, compared with multi-linear regression (MLR) and
      molecular docking, on a set of 93 small molecules that act as inhibitors of BChE
      by use of the inhibitory activities (pIC50 values) of the molecules as target
      values. The statistical results for the linear model built from docking generated
      energy descriptors were: r(2)=0.67, rmsd=0.87, q(2)=0.65 and loormsd=0.90; the
      statistical results for the ligand-based MLR model were: r(2)=0.89, rmsd=0.51,
      q(2)=0.85 and loormsd=0.58; the statistical results for the ligand-based NN model
      were the best: r(2)=0.95, rmsd=0.33, q(2)=0.90 and loormsd=0.48, demonstrating
      that the NN is powerful in analysis of a set of complicated data. As BChE is also
      an established drug target to develop new treatment for Alzheimer's disease (AD).
      The developed QSAR models provide tools for rationalizing identification of
      potential BChE inhibitors or selection of compounds for synthesis in the
      discovery of novel effective inhibitors of BChE in the future.

PMID- 24290067
TI  - Uterine artery rupture during the second stage of labor.

PMID- 24290068
TI  - A meta-analysis of reverse breech extraction to deliver a deeply impacted head
      during cesarean delivery.
AB  - BACKGROUND: During cesarean delivery, extracting a deeply impacted head is a real
      challenge for obstetricians. OBJECTIVES: To compare selected maternal and fetal
      outcome indicators of the "pull" (reverse breech extraction) and "push" methods
      for impacted fetal head extraction during cesarean delivery. SEARCH STRATEGY: A
      computer-based search of the Medline, Cochrane library, and HINARI databases.
      SELECTION CRITERIA: Studies that compared the maternal and perinatal outcomes of
      the push and pull methods for impacted fetal head extraction during cesarean
      delivery were included. DATA COLLECTION AND ANALYSIS: A meta-analysis of Mantel
      Haenszel odds ratios and standardized mean differences from 11 randomized
      comparative and retrospective cohort studies was performed. MAIN RESULTS: In the
      pooled analysis, the risk of uterine incision extension was more than 8 times
      higher with the push method than with the pull method. Blood loss and operation
      time were also increased with the push method, and this method was associated
      with more perinatal deaths and admissions to the neonatal intensive care unit.
      The risk of wound infection was not significantly different between the 2
      methods. CONCLUSIONS: The present meta-analysis demonstrated marked reductions in
      uterine incision extension, blood loss, and operation time with reverse breech
      extraction.

PMID- 24290069
TI  - Retention of endothelial progenitor cells in bone marrow in a murine model of
      endogenous tissue plasminogen activator (tPA) deficiency in response to critical
      limb ischemia.
AB  - BACKGROUND: This study tested the hypothesis that tissue plasminogen activator
      (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization
      from bone marrow to circulation in murine critical limb ischemia (CLI) by
      ligating the left femoral artery. METHODS: Wild-type (C57BL/6) (n=40) mice were
      equally divided into group 1A (sham control), group 2A (CLI), group 3A [control
      tPA (4.0 mg/kg)] and group 4A [CLI-tPA (intravenously at 3 h after CLI)].
      Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group
      1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], and group
      4B (CLI-tPA). RESULTS: The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+,
      CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A,
      respectively (all p<0.01), and were reversed after tPA treatment (3B vs. 3A or 4B
      vs. 4A, p>0.05) at 6 h and 18 h post-CLI. Levels of these biomarkers decreased
      again 14 days after CLI in tPA(-/-) mice compared to those in wild-type between
      the respective groups (all p<0.01). Laser Doppler flowmetry showed a higher ratio
      of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14
      after CLI (all p<0.05). Angiogenesis at protein (CXCR4, SDF-1alpha, VEGF) and
      cellular (CXCR4+, SDF-1alpha+, and CD31+ cells) levels was highest in animals
      with CLI-tPA, significantly higher in mice with CLI only than in sham controls
      for both wild-type and tPA(-/-) mice (p<0.01). CONCLUSION: tPA played an
      essential role in augmenting circulating EPCs, angiogenesis, and blood flow in
      the ischemic limb in a murine model.

PMID- 24290070
TI  - Worldwide patterns of ischemic heart disease mortality from 1980 to 2010.
AB  - BACKGROUND: The trends in the IHD mortality rates vary widely across countries,
      reflecting the heterogeneity in the variation of the exposure to the main risk
      factors and in the access to different management strategies among settings. We
      aimed to identify model-based patterns in the time trends in IHD mortality in 50
      countries from the five continents, between 1980 and 2010. METHODS AND RESULTS:
      Mixed models were used to identify time trends in age-standardized mortality
      rates (ASMR) (age group 35+years; world standard population), all including
      random terms for intercept, slope, quadratic and cubic. Model-based clustering
      was used to identify the patterns. We identified five main patterns of IHD
      mortality trends in the last three decades, similar for men and women. Pattern 1
      had the highest ASMR and pattern 2 exhibited the most pronounced decrease in ASMR
      during the entire study period. Pattern 3 was characterized by an initial
      increase in ASMR, followed by a sharp decline. Countries in pattern 4 had the
      lowest ASMR throughout the study period. It was further divided into patterns 4a
      (consistent decrease in ASMR throughout the period of analysis) and 4b (less
      pronounced declines and highest rates observed mostly between 1996 and 2004).
      There was no correspondence between the geographic or economical grouping of the
      analyzed countries and the patterns found in this study. CONCLUSIONS: Our study
      yielded a new framework for the description, interpretation and prediction of IHD
      mortality trends worldwide.

PMID- 24290071
TI  - Fever after primary percutaneous coronary intervention in ST-segment elevation
      myocardial infarction is associated with adverse outcomes.
AB  - BACKGROUND: Fever is a common finding after primary percutaneous coronary
      intervention (PPCI) in patients with ST-segment elevation myocardial infarction
      (STEMI). However, its prognostic value is not validated yet. OBJECTIVES: This
      study sought to evaluate the impact of fever after PPCI in STEMI on adverse
      clinical outcomes. METHODS: Five hundred fourteen consecutive patients who
      underwent PPCI due to STEMI were enrolled. Body temperature (BT) was checked
      every 6 h for 5 days after PPCI. Patients were divided into two groups according
      to the highest quartile of peak BT; peak BT<=37.6  degrees C (control group) and
      peak BT>37.6  degrees C (fever group). Rates of 1-year major adverse
      cardiovascular events (MACE; death, myocardial infarction, any revascularization)
      were compared. RESULTS: The prevalence of fever group (peak BT>37.6  degrees C)
      was 24.7% (127/514). White blood cell count, highly sensitive C-reactive protein
      and serum cardiac troponin I level were higher in fever group than control group
      (12,162+/-4199/MUL vs. 10,614+/-3773/MUL, p<0.001; 22.9+/-49.4 mg/L vs. 7.4+/-2.5
      mg/L, p=0.001, 16.7+/-36.9 ng/dl vs. 8.70+/-26.2 ng/dl, p=0.027, respectively).
      The frequency of a history of previous myocardial infarction and left ventricular
      ejection fraction was lower in fever group (0.0% vs. 4.7%, p=0.010; 47+/-8 % vs.
      49+/-9 %, p=0.002, respectively). There was no significant difference in
      angiographic characteristics between 2 groups. 1-year MACE rates were higher in
      fever group (11.0% vs. 4.7%, p=0.010). Multivariate analysis revealed fever (OR
      2.358, 95% CI 1.113-4.998, p=0.025), diabetes mellitus as risk factor (2.227,
      1.031-4.812, 0.042), and left anterior descending artery as infarct related
      artery (2.443, 1.114-5.361, 0.026) as independent predictors for 1-year MACE.
      CONCLUSIONS: Fever after PPCI in patients with STEMI is frequently developed and
      it can predict adverse clinical outcome.

PMID- 24290072
TI  - Inverted left atrial appendage.

PMID- 24290073
TI  - Analysis of antimicrobial consumption and cost in a teaching hospital.
AB  - BACKGROUND: The aim of this study is to compare the periods before and after the
      intervention applied using the ATC/DDD method in order to ascertain the rational
      use of antibiotics in a newly established hospital. METHOD: The appropriateness
      of the hospital's antibiotic use, consumption rates and the costs were calculated
      and compared with other hospitals. Based on these data, an intervention has been
      planned in order to raise the quality of antibiotic use. The periods before and
      after the intervention were compared. Between 16 May 2011 and 23 May 2012, data
      were collected from all hospital units by the infectious diseases specialists and
      a point prevalence survey was conducted. Anatomical therapeutic chemical
      classification and the defined daily dose (DDD) methodology were used to
      calculate the antibiotic consumption. RESULTS: On two specific days in 2011 and
      2012, 194 out of 307 patients (63.2%) and 224 out of 412 patients (54.4%)
      received antibiotic treatment, respectively. In 2011 and 2012, the percentage of
      appropriate antibiotic use was 51% and 64.3%, respectively. Both in 2011 and
      2012, inappropriate antibiotic use was found to be significantly higher in
      surgical clinics in comparison to the internal diseases clinics and the ICU. This
      was caused by the high rates of inappropriate perioperative antimicrobial
      prophylaxis observed in surgical clinics. During both years, approximately one
      third of the antibiotics were prescribed for the purposes of perioperative
      prophylaxis, while 88.5% and 43.7% of these, respectively, were inappropriate and
      unnecessary. Cephalosporins, fluoroquinolones, combinations of penicillins
      (including beta-lactamase inhibitors) and carbapenems were the most frequently
      prescribed antibiotics during the study periods. The mean total antibiotic
      consumption was 93.6 DDD/100 bed-days and 63.1 DDD/100 bed-days, respectively.
      The cost of total antibacterial consumption was ? 7901.33 for all the patients (?
      40.72 per infected patient) and ? 6500.26 (? 29.01 per infected patient),
      respectively. CONCLUSION: Each hospital should follow and assess their antibiotic
      use expressed in DDD in order to compare their antibiotic use with national and
      international hospitals (WHO, 2009 [14]).

PMID- 24290074
TI  - Risk factors of mortality among dengue patients admitted to a tertiary care
      setting in Kerala, India.
AB  - Dengue is one of the most serious and rapidly emerging tropical mosquito-borne
      diseases. The state of Kerala in India is hyperendemic for the disease and is one
      of the leading states in the reporting of deaths due to dengue. As primary
      prevention of dengue has had limited success, the prevention of mortality through
      the identification of risk factors and efficient patient management is of utmost
      importance. Hence, a record-based case control study was conducted in the Medical
      College Hospital in Thiruvananthapuram to identify the risk factors of mortality
      in patients admitted with dengue. Dengue patients over 40years of age were 9.3
      times (95% CI; 1.9-44.4) more likely to die compared with younger patients. The
      clinical features associated with mortality from dengue were altered sensorium
      (odds ratio (OR) - 156, 95% CI; 12.575-1935.197), abnormal reflexes (OR - 8.5,
      95% CI; 1.833-39.421) and edema (OR - 13.22, 95% CI; 2.651-65.951). Mortality was
      also higher in those patients with co-morbidities such as diabetes mellitus (OR -
      26, 95% CI; 2.47-273.674) and hypertension (OR - 44, 95% CI; 6.23-315.499). The
      independent predictors of mortality were altered sensorium and hypertension.
      Dengue fever patients with these clinical features and those who are elderly
      should be more rigorously monitored and promptly referred from lower settings
      when required to reduce mortality. 

PMID- 24290075
TI  - A case of Bardet-Biedl syndrome complicated with intracranial hypertension in a
      Japanese child.
AB  - Bardet-Biedl syndrome (BBS) is a rare heterogeneous autosomal recessive disorder
      characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity,
      hypogonadism, learning disability, and renal anomaly that are caused by ciliary
      dysfunction. 16 genes have been associated with the BBS phenotype. Although
      recent pathophysiological studies using animal models have shown that ciliary
      dysfunction may induce hydrocephalus, there have been no reports of BBS with
      intracranial hypertension. We here describe a 9-year-old Japanese girl who was
      diagnosed as having BBS and later received renal transplantation due to chronic
      renal failure. She also exhibited intracranial hypertension, including
      papilledema and increased intrathecal pressure (260-300 mmH2O), but her brain
      magnetic resonance imaging was normal. No genetic abnormalities were detected by
      DNA chip analysis or exome sequencing. Her papilledema improved following
      administration of acetazolamide. This is the first report of a case of BBS
      complicated with intracranial hypertension and its treatment.

PMID- 24290076
TI  - Retropatellar fat pad-derived stem cells from older osteoarthritic patients have
      lesser differentiation capacity and expression of stemness genes.
AB  - BACKGROUND AIMS: The use of retropatellar fat pad-derived mesenchymal stromal
      cells (RFMSCs) for cell-based therapy, particularly for cartilage repair, has
      been reported by several investigators in recent years. However, the effects of
      the donor's age and medical condition on the characteristics of RFMSCs have not
      been well established. The aim of this study was to determine whether age and
      medical condition can reduce the multipotential of stem cells isolated from the
      retropatellar fat pad. METHODS: The RFMSCs were isolated from patients with
      osteoarthritic knee cartilage (degenerative group; 40-60 years old) and compared
      with patients without degenerative knee disease (young group; <40 years old) in
      terms of their growth kinetics, immunophenotype, differentiation ability and
      stemness gene expression. RESULTS: Data showed that RFMSCs from both groups have
      similar growth kinetics and immunophenotype profile at passage 3. However, RFMSCs
      from the degenerative group showed lower adipogenic, osteogenic and chondrogenic
      differentiation ability compared with RFMSCs derived from the young group. The
      stemness gene expression level of RFMSCs derived from the degenerative group was
      lower than that in the young group. RFMSCs from both groups met the minimum
      criteria of mesenchymal stromal cells and have the potential for cartilage
      regeneration. However, RFMSCs from the degenerative group showed lower
      regeneration capability. CONCLUSIONS: These results indicate that older age and
      osteoarthritic condition did affect the multipotential of stem cells derived from
      the retropatellar fat pad under the current prescribed condition. More studies
      will be conducted to clarify whether the age or medical condition contributed
      more to the loss of differentiation capacity and stemness gene expression of
      RFMSCs.

PMID- 24290077
TI  - Interference with AMPA receptor endocytosis: effects on behavioural and
      neurochemical correlates of amphetamine sensitization in male rats.
AB  - BACKGROUND: Behavioural sensitization has been linked to drug craving in both
      clinical and preclinical studies of addiction. Increased motor activity is
      accompanied by enhanced dopamine (DA) release, particularly in the nucleus
      accumbens (NAcc). The neural bases of sensitization are linked to alterations in
      synaptic connections that also underlie learning and memory. The present study
      uses an "interference" peptide, Tat-GluA2(3Y), that blocks long-term depression
      (LTD) at glutamatergic synapses by disrupting the endocytosis of alpha- amino-3
      hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), to explore the
      role of this form of synaptic plasticity in the induction and maintenance of
      sensitization. METHODS: Rats were given 5 injections of d-amphetamine (d-AMPH,
      1.0 mg/kg, intraperitoneal) every second day. Tat-GluA2(3Y), was administered by
      2 different routes (intravenously and intracerebrally to the ventral tegmental
      area [VTA] or to the NAcc) before each injection of d-AMPH. After a 14-day drug
      free period, expression of behavioural sensitization was evoked by a challenge
      injection of d-AMPH (0.5 mg/kg, intraperitoneal). Dopamine efflux in the NAcc was
      measured by high-pressure liquid chromatography with electrochemical detection
      analyses of brain dialysates on days 1, 9 and 24 of the intravenous peptide
      experiment. RESULTS: Systemic administration of Tat-GluA2(3Y) during the
      induction phase blocked maintenance of behavioural sensitization and attenuated
      the maintenance of neurochemical sensitization. Intra-VTA infusion of Tat
      GluA2(3Y) before each administration of d-AMPH did not affect induction, but
      inhibited maintenance and subsequent expression of sensitization, whereas intra
      NAcc infusion of the peptide did not affect induction or maintenance of
      sensitization. LIMITATIONS: The relevance of behavioural sensitization in rodents
      is related to the development of craving and does not provide direct measures of
      drug reinforcement. CONCLUSION: These findings confirm that drug-induced
      neuroplasticity is labile and may be subject to disruption at a time when long
      lasting associations between drug reward and contextual stimuli are formed.
      Furthermore, the unique ability of Tat-GluA2(3Y) to block maintenance of
      behavioural sensitization implicates LTD in the consolidation of essential
      associative memories. Tat-GluA2(3Y) has the unique ability to disrupt functional
      neuroadaptations triggered by repeated psychostimulant exposure and therefore may
      protect against the development of craving and drug seeking behaviours.

PMID- 24290078
TI  - Association between maternal behavior in infancy and adult mental health: a 30
      year prospective study.
AB  - BACKGROUND: Existing theories suggest that the mother-infant relationship has a
      potentially significant effect on long-term adult mental health, but there are
      few empirical data to support this view. Even fewer prior studies have examined
      the specific dynamics of the mother-infant relationship and their association
      with adult mental health. METHODS: A total of 1752 inner-city infants born
      between 1960 and 1965 were followed prospectively as a part of the Collaborative
      Perinatal Project (CPP) and the Johns Hopkins Pathways to Adulthood Study.
      Multiple observations of development and an extensive adult interview were
      performed. Maternal behavior was observed and systematically rated at the
      infant's 4-month pediatric neurological evaluation and at 8 months by a
      developmental psychologist. Factor analysis was used to organize the maternal
      behavior variables into different types of dysfunctional mother-infant
      relationships. Adult mental health was assessed at the follow-up interview, when
      the infant had reached the age of 27-33 years, by the General Health
      Questionnaire (GHQ) and self-perception of current mental health. RESULTS: There
      was a significant association between unsupportive maternal behavior at 8 months
      and subsequent poor adult mental health (Fisher's exact test, p=0.026). There was
      no association between overly involved maternal behavior and poor mental health
      as an adult. After adjustment for potential confounding variables, the elevated
      rates of poor adult mental health in children of mothers who exhibited
      unsupportive maternal behavior at 8 months persisted (OR=1.41 [95% CI=1.00-1.97],
      p<0.05). CONCLUSION: Infants who experience unsupportive maternal behavior at 8
      months have an increased risk for developing psychological sequelae later in
      life.

PMID- 24290080
TI  - World War II-related post-traumatic stress disorder and breast cancer risk among
      Israeli women: a case-control study.
AB  - BACKGROUND: Several studies have suggested that post-traumatic stress disorder
      (PTSD) is related to adverse health outcomes. There are limited data on PTSD and
      cancer, which has a long latency period. We investigated the association between
      World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among
      Jewish WWII survivors and examined whether this association was modified by
      exposure to hunger during WWII. METHODS: We compared 65 BC patients diagnosed in
      2005 through 2010 to 200 population-based controls who were members of various
      organizations for Jewish WWII survivors in Israel. All participants were born in
      Europe, lived at least six months under Nazi rule during WWII, and immigrated to
      Israel after the war. We estimated PTSD using the PTSD Inventory and applied
      logistic regression models to estimate the association between WWII-related PTSD
      and BC, adjusting for potential confounders. RESULTS: We observed a linear
      association between WWII-related PTSD and BC risk. This association remained
      significant following adjustment for potential confounders, including obesity,
      alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and
      total number of traumatic life events (OR = 2.89, 95% CI = 1.14-7.31). However,
      the level of hunger exposure during WWII modified this effect significantly.
      CONCLUSIONS: These findings suggest an independent association between WWII
      related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by
      hunger, a novel finding. Future research is needed to further explore these
      findings.

PMID- 24290079
TI  - Psychopathology in bariatric surgery candidates: a review of studies using
      structured diagnostic interviews.
AB  - Psychiatric disorders are not uncommon among severely obese patients who present
      for bariatric surgery. This paper (1) reviews the results of the published
      studies using the structured interviews to assess psychopathology in bariatric
      surgery candidates; (2) compares the prevalence rates of psychiatric disorders
      across these studies with the data from other population samples; and (3)
      assesses whether sociodemographic variables appear to affect these prevalence
      rates. We searched online resources, PubMed, PsychINFO and reference lists of all
      the relevant articles to provide an overview of evidence so far and highlight
      some details in the assessment and comparisons of different samples in different
      countries. The prevalence estimates in the non-treatment obese group did not
      appear to differ substantially from the general population group in the US or the
      Italian population samples, although they were relatively higher for the German
      population. However, the rates of psychopathology in the bariatric surgery
      candidates were considerably higher than the other two population groups in all
      the samples. Overall, the most common category of lifetime Axis I disorders in
      all the studies was affective disorders, with anxiety disorders being the most
      common category of current Axis I disorders. Certain demographic characteristics
      are also associated with higher rates of psychopathology, such as, female gender,
      low socioeconomic status, higher BMI. Overall, methodological and
      sociodemographic differences make these studies difficult to compare and these
      differences should be taken into account when interpreting the results. 

PMID- 24290081
TI  - Relative effect of socio-economic status on the health-related quality of life in
      type 2 diabetic patients in Iran.
AB  - INTRODUCTION AND AIMS: Type II diabetes mellitus (T2DM) is a progressing epidemic
      and a major cause of mortality and morbidity worldwide. The quality of life (QoL)
      of diabetic patients has been strongly influenced by socioeconomic status (SES)
      in developed countries. Therefore, the QoL improvement is considered to be a
      major goal in diabetes control program. In this context, there is no reliable
      evidence for developing countries. In this study, the relative association of SES
      with health-related quality of life (HRQoL) was assessed in patients with T2DM in
      Iran. METHOD: The "Cost estimation of Type 2 Diabetes in Iran" was used for
      secondary data analysis. The socio-economic status has been assessed by
      Categorical principal component analysis (CATPCA) techniques and HRQoL, using EQ
      5D Visual Analog Scale, modified for digit preferences. Age, gender, education,
      occupation, SES, marital status, residency, education (T2DM related), diagnostic
      methods, number of annual care, type of treatment and Duration of disease
      awareness were used as independent variables in the multivariable linear
      regression model. Statistical analysis was performed using Stata software version
      11.2. RESULTS: The response rate was 88.6%. Out of 3472 patients, 2128 were
      female and about 78.7% were from urban areas. All variables associated with T2DM
      were significant at the level of 0.05 except, the type of treatment, residency
      and education. Standardized regression coefficient for SES was estimated as 0.106
      (p-value<0.0001). CONCLUSION: It seems that the SES of households in developing
      countries has a meaningful effect on the HRQoL of patients with T2DM as well as
      developed countries.

PMID- 24290082
TI  - Pregnancy complications, mental health-related problems and type 2 diabetes
      mellitus in Malaysian women.
AB  - AIMS: The aim of this study was to investigate the association between pregnancy
      complications, mental health-related problems, and type 2 diabetes mellitus
      (T2DM) in Malaysian women. MATERIALS AND METHODS: A case-control study of women
      with T2DM (n=160) matched by age range to controls without T2DM (n=160). Data
      were collected in the Negeri Sembilan and PutraJaya regions in Malaysia, from two
      hospital outpatient clinics, PutraJaya Hospital and Tuanku Jaa'far Hospital
      Seremban, and one health clinic at Seremban. Validated, interviewer-administered
      questionnaires were used to obtain the data. The unadjusted and adjusted
      estimates were calculated using the Mantel-Haenszel method. RESULTS: Neither
      depression (RR 0.74, 95% CI: 0.39-1.41) nor anxiety (RR 1.00, 95% CI: 0.53-1.88)
      symptoms increased the risk of T2DM significantly. However, gestational diabetes
      (RR 1.35, 95% CI: 1.02-1.79), and >=3 pregnancies (RR 1.39, 95% CI: 1.08-1.79)
      were significant risk factors for the development of T2DM. T2DM was not a
      significant risk factor for either depression (RR 1.26, 95% CI: 0.91-1.74) or
      anxiety symptoms (RR 1.13, 95% CI: 0.59-2.19). CONCLUSION: In this study, T2DM is
      not a significant risk factor for depression and anxiety; similarly, neither are
      depression and anxiety significant risk factors for T2DM. Although prevalence of
      depression and anxiety is not alarming, the findings reported here should alert
      clinicians to screen and treat anxiety and depression in people with diabetes and
      also note the importance of monitoring women with complications in pregnancy for
      risk of later T2DM.

PMID- 24290083
TI  - Determinants of plasma triglyceride levels in a multiethnic working class
      Caribbean population: effect of ethnicity, diet and obesity.
AB  - AIMS: Objective of the study is to identify the predictors of plasma
      triglycerides. MATERIALS AND METHODS: A stratified random sample of university
      staff categories underwent measurements of anthropometry, blood pressure, and
      fasting blood glucose, insulin, lipids, CRP and homocysteine. Dietary intakes
      were assessed using duplicate 24h recalls. HOMA-IR was calculated. Stepwise,
      multivariate regression analysis was performed with TAG as the dependent
      variable. RESULTS: The sample (n=251) was 55% females with a mean age of 44.9+/
      9.7 years. African ancestry comprised 43%, followed South Asian 30% and mixed
      ethnicity 27%. Prevalence of obesity was 19.4%, insulin resistance 22.7% and
      metabolic syndrome 21.6%. Males had significantly higher (p<0.01) triglycerides
      and VLDL and lower HDL than females. Africans had significantly lower
      triglycerides and cholesterol than South Asians and Mix. Triglycerides were
      significantly (p<0.01) correlated with glucose, cholesterol, insulin, CRP,
      systolic, diastolic blood pressure, WC, BMI, age and components of MS. Glucose,
      cholesterol, insulin and total energy intake predicted TAG, to varying extents,
      in all participants (R(2)=45.1%), males (R(2)=40.3%), females (R(2)=56.0%),
      Africans (R(2)=35.0%), TSA (R(2)=31.5%) and mix (R(2)=51.0%). CONCLUSIONS:
      Africans have lower triglycerides and cholesterol than South Asians and mix.
      Major predictors of triglycerides were fasting glucose and cholesterol
      independent of gender and ethnicity.

PMID- 24290084
TI  - Study of serum insulin levels in patients of euglycemic essential hypertension: a
      cross sectional study in North Indian population.
AB  - OBJECTIVE: Essential hypertension is associated with multiple metabolic
      abnormalities, among them one of the most important is hyperinsulinemia.
      Hyperinsulinemia has been suggested as being responsible for the increased
      arterial pressure in patients with essential hypertension. But this is
      contradicted by the finding that all patients of essential hypertension are not
      hyperinsulinemic. The present study was conducted to explore the hypothesis that
      hyperinsulinemia plays a pathogenic role in hypertension in euglycemic North
      Indian population. METHODS AND MATERIALS: 120 subjects were studied (60
      hypertensive and 60 normotensive). Blood pressure, fasting insulin levels, lipid
      profile and BMI were calculated for both the groups. Statistical analysis was
      done using online statistical software freely at www.openepi.com. RESULTS:
      Hypertensive subjects were characterized by increased fasting insulin levels
      (16.77+/-7.62 vs. 8.84+/-2.04MUIU/ml, p<0.01), increased BMI (p<0.01) and
      dyslipidemia, i.e. increased total cholesterol, high serum triglycerides, high
      LDL-C and low HDL-C with p<0.01. There was a positive correlation of fasting
      insulin levels with BMI, total cholesterol and LDL-C (p<0.01) and a negative
      correlation with HDL-C (p<0.05). However, serum insulin levels showed a non
      significant correlation with mean systolic and mean diastolic blood pressure
      (p>0.05). CONCLUSIONS: Our study showed a significant increase in serum insulin
      levels in hypertensive patients thereby supporting a possible pathogenic role of
      insulin resistance in onset of hypertension even when the fasting blood sugar is
      within normal limits.

PMID- 24290085
TI  - Feto-maternal outcomes in women with and without gestational diabetes mellitus
      according to the International Association of Diabetes and Pregnancy Study Groups
      (IADPSG) diagnostic criteria.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is responsible for majority of
      pregnancies complicated with diabetes mellitus. Both the screening (universal vs.
      selective) and the diagnostic criteria of GDM has been the subject of
      considerable controversy. METHODS: This prospective cohort study was undertaken
      at Pondicherry Institute of Medical Sciences, Puducherry from August 2011 to July
      2012. All the patients attending antenatal clinic underwent oral glucose
      tolerance test (OGTT) with 75g of anhydrous glucose between 24 and 32 weeks of
      gestation. Those patients diagnosed as GDM according to IADPSG diagnostic
      criteria were treated with diet and physical activity with or without insulin.
      All the antenatal and perinatal outcomes were noted. RESULTS: The prevalence of
      GDM in our study was 27% (83/304). Out of all the GDM patients, 87% (72/83) cases
      were diagnosed by raised FBS alone or with other two values. A significant family
      history of diabetes mellitus was found among GDM mothers compared to non-GDM
      group (10.8% vs. 3.6%, p=0.01). Insulin was required only in 8 patients for
      glycemic control. The GDM patients delivered at significantly lower gestational
      age (p=0.02) with more antenatal complications (25% vs. 12%, p=0.02). Among
      neonatal outcomes, there was a significant difference only in the need for NICU
      admission>24h between GDM and non-GDM groups (p=0.02). CONCLUSION: The prevalence
      of GDM increases with universal screening using IADPSG diagnostic criteria in
      India. The antenatal complications are present in up to one fourth of these
      patients.

PMID- 24290086
TI  - Defining a cutoff point for vitamin D deficiency based on insulin resistance in
      children.
AB  - BACKGROUND: Vitamin D deficiency is a common worldwide problem. Low levels of
      serum 25-hydroxy vitamin D [25(OH)D], as a marker of vitamin D deficiency, have
      been linked to a wide field of health problems, including metabolic diseases such
      as insulin resistance, type 1 and type 2 DM. There is no universal definition for
      cutoff value of vitamin D deficiency and it seems that it varies in different
      populations. OBJECTIVE: Most previous studies have used a start rise of PTH as a
      criteria to detect threshold of serum 25(OH)D, However, the aim of this study was
      to determine a cutoff point of serum 25(OH)D for vitamin D deficiency based on
      HOMA-IR. MATERIALS AND METHODS: Two hundred and ninety seven healthy children
      (aged 7-11 years) were enrolled. Serum 25(OH)D and PTH were measured and HOMA-IR
      was calculated. The ROC curve was utilized to obtain a cutoff of vitamin D
      deficiency based on HOMA-IR. RESULTS: 25(OH)D concentrations were inversely
      correlated with HOMA-IR levels (Spearman's r=-0.14, p=0.016). Serum 25(OH)D
      cutoff point was 11.6ng/mL (29nmol/L) in relation with HOMA-IR >2.1. By using
      this cutoff value, the prevalence of vitamin D deficiency was 43.4% in this study
      population of healthy children. CONCLUSION: We found that serum 25(OH)D levels
      are inversely associated with insulin resistance. These results suggest that in
      MetS patients it may benefit to determine cutoff value of 25(OH)D levels based on
      HOMA-IR.

PMID- 24290087
TI  - Synergy of iron, high sensitivity C-reactive protein and ceruloplasmin with
      oxidative stress in non-diabetic normo-tensive South Indian obese men.
AB  - BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis
      of obesity and its related complications. Previous studies have suggested a
      potential link between obesity and altered iron metabolism. The present study was
      designed to evaluate iron, C-reactive protein, ceruloplasmin and oxidative stress
      and their association, if any, in non-diabetic normo-tensive South Indian obese
      men. METHODS: 30 obese men and 30 age-matched males with normal body weight were
      recruited in the study. Serum iron, copper, ceruloplasmin, high sensitivity C
      reactive protein (hs-CRP), malondialdehyde, protein carbonyl, total oxidant
      status and total antioxidant status were estimated in all the subjects. RESULTS:
      Serum iron, ceruloplasmin, high sensitivity C-reactive protein (hs-CRP),
      malondialdehyde (MDA), protein carbonyl and total oxidant status were
      significantly increased and total antioxidant status was significantly reduced in
      obese men, compared to controls. Linear regression analysis shows highly
      significant positive association of iron with hs-CRP. CONCLUSION: The data from
      the present study concludes that oxidative stress parameters, hs-CRP, iron and
      ceruloplasmin were significantly elevated in obese Indian men, suggesting they
      are more prone to develop cardiovascular disease, than age-matched men with
      normal body weight.

PMID- 24290088
TI  - Prevalence of the metabolic syndrome and its correlation with the cardiovascular
      health status in stroke- and ischemic heart disease-free Ecuadorian
      natives/mestizos aged >=40 years living in Atahualpa: a population-based study.
AB  - AIMS: Epidemiologic studies assessing cardiovascular risk factors affecting a
      given population may prove cost-effective to reduce the burden of cardiovascular
      diseases in the developing world. We evaluated the prevalence of the metabolic
      syndrome in Atahualpa, a village representative of rural coastal Ecuador.
      METHODS: Prevalence of the metabolic syndrome and its correlation with the
      cardiovascular (CVH) status was assessed in a door-to-door survey performed in
      stroke- and ischemic heart disease-free Ecuadorian native/mestizos aged >=40
      years. RESULTS: The metabolic syndrome was diagnosed in 288 (55.7%) out of 517
      persons. Worst individual components were: increased waist circumference (75%),
      increased fasting glucose (68.1%) and high blood pressure (56.5%). Prevalence of
      individual components of this condition varied according to age, gender,
      education, and alcohol intake. However, no differences were found in the odds for
      having the metabolic syndrome when persons were stratified according to these
      parameters. A poor CVH status was found in 80.2% persons with and in 55.9%
      without the metabolic syndrome (p<0.0001). CONCLUSIONS: Prevalence of the
      metabolic syndrome in Atahualpa is high. Most persons with the metabolic syndrome
      also have a poor CVH status. However, sizable subsets only have either the
      metabolic syndrome or a poor CVH status. Stratification of cardiovascular risk
      according to whether the person has both, one, or none of these two sets of risk
      factors would be of value to evaluate if the metabolic syndrome, a poor CVH
      status or the combination of both, better predict the occurrence of vascular
      outcomes in the long-term follow-up.

PMID- 24290089
TI  - Efficacy of liraglutide as a follow-up therapy after resolution of glucotoxicity
      with intensive insulin therapy.
AB  - OBJECTIVE: To assess the utility of liraglutide, a GLP-1 receptor agonist, as
      additional therapy following resolution of glucotoxicity with insulin therapy.
      METHODS: The subjects were 13 Japanese patients with short-duration type 2
      diabetes mellitus (2.0 +/- 2.1 years). At first, treatment with insulin therapy
      consisted of bolus insulin before each meal and basal insulin at bed time
      commenced to improve every preprandial glucose levels below 130 mg/dL. Then,
      insulin therapy was replaced with liraglutide monotherapy in case in which 50% or
      more self-monitoring of blood glucose (SMBG) tests revealed preprandial glucose
      levels of less than 130 mg/dL at least for one month. Liraglutide dosing was
      initiated at 0.3 mg/day and increased in weekly or biweekly increments of 0.3
      mg/day, to the maximum permissible dose (in Japan) of 0.9 mg/day. The
      participants were treated with liraglutide for 24 weeks. RESULTS: The average
      insulin therapy period was 13.2 +/- 5.4 weeks, and insulin therapy significantly
      improved HbA1c values from 12.4% +/- 1.6% to 6.8% +/- 0.9% (P < 0.05). After
      improvement of hyperglycemia with insulin therapy and switching to liraglutide
      monotherapy for 24 weeks, HbA1c values remained constant (6.2% +/- 1.0% at week
      24) and the rates of hypoglycemic episodes significantly decreased (P < 0.05).
      CONCLUSIONS: These data suggest that liraglutide is proposed as an alternative
      follow-up therapy subsequent to eliminate glucotoxicity with insulin therapy.

PMID- 24290090
TI  - The relationship of metabolic syndrome and constitutional medicine for the
      prediction of cardiovascular disease.
AB  - The concept of Sasang Constitutional Medicine (SCM) has been in existence in
      Traditional Korean Medicine for more than 100 years. SCM consists of 4 different
      types; So-Eum (SE), So-Yang (SY), Tae-Eum (TE), and Tae-Yang (TY). In Western
      medicine, it is more like stratifying individuals according to phenotypic
      expression. It is of great importance that the Sasang constitution type be
      evaluated accurately and recognized by the medical communities for prevention,
      early diagnosis and treatment of cardiovascular diseases (CVD). SUBJECTS AND
      METHODS: From the Ansung-Ansan prospective cohort study, 10,038 participants were
      recruited from years 2001-2002. Of 10,038 original participants, 3022 subjects
      underwent Sasang Constitutional Type (SCT) evaluation. The Cox proportional
      hazard model was used to predict CVD during the ten year follow-up period.
      RESULTS: Of 3022 participants, SCT classified into 364 (12%) SE, 1053 (34.8%) SY,
      1605 (53.1%) TE, and no TY. Three hundred seventy nine (16%) newly developed CVD
      during the following period, yielding 10-year cumulative incidence of 160/1000
      person. The frequency of CVD within three SCT without metabolic syndrome (MetS)
      shows 13.4% in SE, 13.6% in SY, and 14.3% in TE, respectively (p=NS). The CVD
      events were significantly different among the types when MetS was present. The
      demographic and clinical characteristics revealed the TE group was significantly
      older, more obese, higher blood pressure, glucose values, and lipid profiles
      levels. The frequency of MetS and type 2 diabetes mellitus (T2DM) was also higher
      in TE type than either SE and SY types (all p<0.001). The Cox proportional hazard
      analysis revealed age, female gender, rural residence, higher ALT level, and
      lower beta-cell function remain as an independent risk factor, as well as SY with
      MetS (RR=1.838 (95% CI 1.23-2.74), p=0.003). Furthermore, 10 year CVD survival
      rate was 86.4% in no MetS group, 83.4% in TE, 79.6% in SE, and 76.4% in SY all
      with MetS (p<0.001). CONCLUSIONS: The findings from this study suggest MetS
      increases risk for CVD in certain physical conditions like SY type. Therefore, we
      would like to suggest that SCT is a strong indicator for CVD.

PMID- 24290091
TI  - Assessment of serum leptin and resistin levels in association with the metabolic
      risk factors of pre- and post-menopausal rural women in South India.
AB  - OBJECTIVES: Menopausal status is related with weight gain, abnormal lipid and
      glucose metabolism leading to metabolic syndrome susceptibility. The aim of this
      study is to determine circulating serum leptin and resistin levels and to
      correlate these levels in relationship with the metabolic factors in pre- and
      post-menopausal women. METHODS: A cross-sectional study has been carried out for
      34 subjects who were in post-menopause and 31 subjects who had regular
      menstruation in south Indian rural women. Anthropometric indices, blood pressure,
      fasting blood sugar (FBS), fasting lipid profile, fasting leptin and resistin
      levels were measured. RESULTS: In a total of 65 subjects, the mean age of pre
      menopausal group was 38.65+/-6.21 and that of post-menopausal group was 55.32+/
      6.32. Fasting serum leptin level was increased considerably in post-menopausal
      women when compared to pre-menopausal women (P=0.018). Resistin has no
      significant relationship with metabolic factors except Body Mass Index (BMI) in
      both the groups. Triglycerides and FBS were lower in pre-menopausal group when
      compared to post-menopausal group (P<0.001). Leptin was well correlated with BMI
      in pre-menopausal women (r(2)=0.7120, P<0.0001) as well as post-menopausal women
      (r(2)=0.2470, P=0.0028). Leptin also had significant correlation with FBS in both
      pre (r(2)=0.1373, P=0.0402) and post-menopausal women (r(2)=0.2141, P=0.0401).
      Systolic blood pressure was positively associated with the leptin levels in post
      menopausal women (P<0.001). CONCLUSION: Leptin was found to have significant
      association with metabolic factors when compared to resistin in pre- and post
      menopausal women and there is no doubt that association of BMI and FBS elevates
      the level of leptin in both the category.

PMID- 24290092
TI  - Serum levels of TNF-alpha in peripheral neuropathy patients and its correlation
      with nerve conduction velocity in type 2 diabetes mellitus.
AB  - OBJECTIVE: To compare serum levels of TNF-alpha in patients of peripheral
      neuropathy and patients without neuropathy in type 2 diabetes mellitus. MATERIAL
      AND METHODS: This cross sectional study was conducted in diagnosed type 2
      diabetes mellitus patients. They were divided in groups, Group I (n=37) with
      clinically detectable diabetic peripheral neuropathy of shorter duration and
      Group II (n=27) with clinically detectable diabetic peripheral neuropathy of
      longer duration. They were compared with patients without clinical neuropathy
      (n=22), clinical diagnosis was based on neuropathy symptom score (NSS) and
      neuropathy disability score (NDS) for signs. Blood samples were collected for
      baseline investigations and estimation of serum TNF-alpha. Nerve conduction
      velocity was measured in both upper and lower limbs. Median, Ulnar, Common
      Peroneal and Posterior Tibial nerves were selected for motor nerve conduction
      study and Median and Sural nerves were selected for sensory nerve conduction
      study. RESULTS: The comparisons were done between various clinical and
      biochemical parameters in clinically detectable and undetectable peripheral
      neuropathy groups of type 2 diabetes mellitus. The study showed raised serum
      levels of TNF-alpha in peripheral neuropathy patients and significant correlation
      with nerve conduction velocity. CONCLUSION: High level of TNF-alpha in serum of
      T2DM patients with neuropathy shows possible contribution in development of
      neuropathy. Due to its independent association this cytokine might be used as
      biomarker for diabetic peripheral neuropathy.

PMID- 24290093
TI  - Pioglitazone--do we really need it to manage type 2 diabetes?
AB  - Over the last few years a number of important drugs like rofecoxib,
      rosiglitazone, gatifloxacin (in diabetics) have lost their position in disease
      management. The newest controversy revolves around Pioglitazone, a
      thiozolidindione, which improves insulin sensitivity and is reputed to have
      cardioprotective actions, but is riddled with several controversies related to
      weight gain, distal fractures of long bones, recent reports of bladder cancer and
      others. There are now new groups of drugs, which have been introduced with
      stringent FDA approval. These include DPP-4 inhibitors, GLP-1 analogues and
      bromocriptine (old wine in a new bottle). Early in 2013 we are also looking at
      the launch of another new agent - SGLT-2 inhibitors. These newer agents are
      associated with not only a significant glucose lowering effect but also positive
      extra-glycaemic benefits principally in the areas of hypoglycaemia and weight
      gain. This raises a very important question - do we really need such a
      controversial agent when such a plethora of agents are available to us with
      possibly better metabolic profile than pioglitazone? This review addresses this
      highly contentious area dissecting the pros and cons as we see it. 

PMID- 24290094
TI  - Diabetes and cancer: a 2013 synopsis.
AB  - Diabetes, in particular type 2 diabetes, and cancer are two diseases that appear
      to be associated. Numerous epidemiological studies indicate indeed that diabetes
      increases the incidence of several tumors. Chronic hyperglycemia and/or insulin
      resistance with compensatory hyperinsulinemia could account for the association.
      On the other hand, the interpretation of the link between diabetes and cancer
      could be influenced by therapeutical interferences. Considering all these data
      together, cancer should be considered as a "new potential complication" of
      diabetes and integrated in the follow-up of diabetic subjects. 

PMID- 24290095
TI  - Microwave ablation of osteoid osteomas using dynamic MR imaging for early
      treatment assessment: preliminary experience.
AB  - PURPOSE: To evaluate the efficacy of microwave ablation for osteoid osteomas by
      using dynamic contrast-enhanced magnetic resonance (MR) imaging in early
      treatment assessment. MATERIALS AND METHODS: Ten patients (two female, eight
      male; mean age, 28 y; range, 16-47 y) presenting with osteoid osteomas were
      treated between June 2010 and December 2012 with the use of computed tomography
      (CT)-guided microwave ablation. Osteoid osteomas were found at the femoral neck
      (n = 4), tibia (n = 3), calcaneus (n = 1), navicular bone (n = 1), and dorsal rib
      (n = 1). Dynamic contrast-enhanced MR imaging at 3.0 T was performed 1 day before
      microwave ablation and again after ablation. The procedure was considered
      successful if the signal intensity (SI) of the lesion on MR imaging decreased by
      at least 50% and the patient was pain-free within 1 week of intervention.
      RESULTS: All patients were pain-free within 1 week after microwave ablation and
      remained so during the 6 months of follow-up. No major or minor complications
      developed. On average, SI of the lesions decreased by 75% (range, 55.5%-89.1%)
      after treatment. The difference in lesion SI before versus after ablation was
      significant by t test (P < .0001; confidence interval, 120.26-174.96) and
      Wilcoxon test (P = .0020). CONCLUSIONS: Microwave ablation treatment of osteoid
      osteoma was highly successful, without any complications observed. Dynamic
      contrast-enhanced MR imaging is a useful tool for diagnosing osteoid osteoma and
      evaluating treatment.

PMID- 24290096
TI  - Percutaneous interventions in failing "necklace" hemodialysis grafts: long-term
      outcomes.
AB  - PURPOSE: To determine primary and secondary patency after percutaneous
      interventions for malfunctioning anterior chest wall ("necklace") arteriovenous
      grafts (AVGs) for hemodialysis. MATERIALS AND METHODS: Records of six consecutive
      patients with subclavian artery-to-contralateral subclavian vein necklace AVGs
      were reviewed. Patients underwent 34 procedures, including 28 balloon
      angioplasties, 24 pharmacomechanical thrombolyses, and six stent placements.
      Patency intervals after graft placement and after first intervention were
      calculated. RESULTS: After 3 months, primary and secondary patency rates were 33%
      (two of six grafts) and 67% (four of six grafts), respectively. At 12 months,
      primary and secondary patency rates were 17% (one of six grafts) and 50% (three
      of six grafts), respectively. Median and mean primary patency times were 49 and
      374 days, and median and mean secondary patency times were 293 and 575 days,
      respectively. The anatomic success rate of percutaneous interventions in
      malfunctioning AVGs was 97% (33 of 34 cases). At 3 years after implantation, the
      graft patency rate was 57% (four of seven grafts). CONCLUSIONS: Percutaneous
      interventions were effective at maintaining patency in failing necklace AVGs.
      However, their primary and secondary patency were inferior to those cited in
      extremity AVG guidelines set forth by the Society of Interventional Radiology.

PMID- 24290097
TI  - Radiofrequency ablation of hepatic cysts: evaluation of therapeutic efficacy.
AB  - PURPOSE: To evaluate therapeutic efficacy of radiofrequency (RF) ablation for
      treatment of hepatic cysts with the use of a single cooled electrode after
      aspiration of the cyst contents. MATERIALS AND METHODS: Fourteen hepatic cysts
      (mean diameter, 7.8 cm; range, 3.7-12.7 cm) in 14 patients treated by RF ablation
      during a 3-year period were retrospectively reviewed. RF ablation was performed
      after aspiration of the cyst contents until a cyst measured no more 3 cm in
      diameter. The volumes of each cyst on computed tomography (CT) were measured
      before and after RF ablation, and volume reduction rates were calculated.
      RESULTS: Follow-up CT was performed a mean of 437 days after RF ablation (range,
      32-1,326 d). One cyst was surgically removed because of regrowth. Nine had a
      volume reduction rate greater than 75%. Eight of nine cysts 8.5 cm in diameter or
      smaller markedly decreased in volume (mean reduction rate, 93.6%; range, 76.8%
      100%). Cysts 8.5-12.0 cm in diameter (n = 4) showed a 61.7% reduction rate
      (range, 26.0%-98.8%). The mean volume reduction rate was 83.5% (range, 8.1%-100%)
      in the nine cysts with less than 10 mL of residual fluid after aspiration,
      compared with 43.2% in the five cysts with more than 10 mL of residual fluid. The
      volume reduction rate was 34.4% in septated cysts after aspiration, in contrast
      to 83.0% in nonseptated cysts. There were no major complications from RF
      ablation. CONCLUSIONS: RF ablation may be effective for the treatment of benign
      hepatic cysts and may be considered as an alternative to conventional
      sclerotherapy or surgery.

PMID- 24290098
TI  - Arterial portography during transarterial chemoembolization: still a necessity in
      the age of contrast-enhanced cross-sectional imaging?
AB  - PURPOSE: To evaluate the necessity of arterial portography (AP) if a patent
      portal vein is seen on imaging before transarterial chemoembolization. MATERIALS
      AND METHODS: All patients who underwent transarterial chemoembolization between
      January 2004 and July 2011 were retrospectively recruited. The study included 131
      patients (100 men, 31 women) undergoing 243 transarterial chemoembolization
      procedures. AP was performed during 93 procedures. The mean time interval between
      imaging performed before transarterial chemoembolization and the transarterial
      chemoembolization procedure was 46.5 days (range, 0-161 d). RESULTS: AP did not
      detect any new cases of portal vein thrombosis (PVT) when imaging performed
      transarterial chemoembolization showed a patent portal vein. Imaging performed
      after transarterial chemoembolization revealed one main PVT, one left PVT
      extending into the main portal vein, two left PVT, and one right PVT. When
      imaging performed before transarterial chemoembolization showed a patent portal
      vein and AP was omitted, imaging performed after transarterial chemoembolization
      showed one case of main PVT, two right PVT, and two left PVT. In both groups,
      there was no significant difference in mortality (P = .673) or morbidity (P =
      .581) related to transarterial chemoembolization. CONCLUSIONS: AP is unnecessary
      if transarterial chemoembolization is performed within a reasonable time frame
      following computed tomography or magnetic resonance imaging that showed a patent
      portal vein. Omitting AP potentially reduces contrast material and radiation
      burden to both the patient and the operator.

PMID- 24290099
TI  - Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma
      with portal vein invasion: safety, efficacy, and prognostic factors.
AB  - PURPOSE: To evaluate the safety and efficacy of transarterial chemoembolization
      and to identify the prognostic factors associated with survival in patients with
      hepatocellular carcinoma (HCC) and portal vein (PV) invasion. MATERIALS AND
      METHODS: From January 2006 to March 2012, 50 patients with HCC invading into the
      PV (Barcelona Clinic Liver Cancer stage C) were treated with transarterial
      chemoembolization. The parenchymal tumor and PV tumor were confirmed by
      multidetector computed tomography (CT) and angiography. There were 14 patients
      with right PV tumor, 12 patients with left PV tumor, and 24 patients with main PV
      tumor. The response was evaluated by multidetector CT using Response Evaluation
      Criteria in Solid Tumors. Patients with residual tumors received repeated
      transarterial chemoembolization every 6-8 weeks unless the patients achieved
      complete remission or developed contraindications. RESULTS: The median survival
      period of the entire group was 6.2 months (range, 1.7-50.9 mo), and the overall
      response rate was 42% (21 of 50 patients). The 6-month, 12-month, 24-month, and
      36-month survival rates were 54%, 22%, 10%, and 8%. There were no instances of 30
      day mortality or acute liver failure related to transarterial chemoembolization.
      The median survival of the 21 responders was 10.5 months, and the median survival
      of the 29 nonresponders was 5.5 months (P < .001). In both univariate and
      multivariate analyses, only the response to transarterial chemoembolization
      (hazard ratio = 0.25, P < .001) and the absence of ascites (hazard ratio = 0.24,
      P = .01) were significant prognostic factors. CONCLUSIONS: Transarterial
      chemoembolization is a safe and effective treatment for HCC with major PV
      invasion. The response to transarterial chemoembolization and the ascites status
      were the most significant predictive factors for prolonged survival.

PMID- 24290101
TI  - Hexabromocyclododecanes in crucian carp and sediment from the major rivers in
      Korea.
AB  - The concentration of hexabromocyclododecanes (HBCDs) was measured in crucian carp
      muscles and eggs and in surrounding sediments collected from the 3 major rivers
      in Korea. HBCDs were detected in all carp and sediment samples, indicating
      widespread contamination of this area by HBCD flame retardants. The ?HBCD (sum of
      alpha-, beta-, and gamma-HBCDs) concentrations ranged from 0.19 to 13 ng g(-1)dry
      wt in sediments, 1.7 to 7.2 ng g(-1)lipid wt in carp eggs, and 4.8 to 6.6 ng g(
      1)lipid wt in the muscle of carp. The alpha-diastereomer predominated in the
      crucian carp and gamma-diastereomer predominated in sediments, accounting for 76%
      and 77% to the ?HBCD, respectively. The ?HBCD concentrations in carp and sediment
      samples collected along the rivers were higher than those in samples collected
      from an isolated pond, suggesting that the rivers are likely contaminated by
      HBCDs from the upstream or the environment surrounding the rivers. The
      diastereomer ratios in carp were different from those in commercial mixtures due
      to the enrichment of alpha-diastereomer in carp. The origin of this transition,
      however, is yet not known, since various transformation processes can lead to a
      change from the diastereomer ratio in commercial mixtures to that observed in the
      environment.

PMID- 24290103
TI  - Intestinal permeability of oxytetracycline from chitosan-montmorillonite
      nanocomposites.
AB  - A nanocomposite based on chitosan and montmorillonite was developed as carrier to
      improve oral bioavailability of oxytetracycline. The nanocomposite was prepared
      by simple solid-liquid interaction and loaded with the drug. The loaded
      nanocomposite was characterized by X-ray powder diffraction, thermal analysis,
      FTIR spectroscopy and zeta potential. Caco-2 cell cultures were used to evaluate
      in vitro cytotoxicity and drug permeation. Confocal laser scanning microscopy was
      also performed to evaluate the eventual entrapment of drug into the Caco-2 cells.
      Results showed that the nanocomposite was internalized into the cells and
      effectively enhanced drug permeation, being also biocompatible towards Caco-2
      cells. 

PMID- 24290102
TI  - Nanoemulsification of pseudo-ceramide by molecular association with
      mannosylerythritol lipid.
AB  - Ceramide molecules in water-based solutions readily attract each other to form
      molecular crystals, which seriously hampers to diversify their formulations. This
      paper describes a facile method that allows fabrication of stable ceramide
      emulsions through an effective molecular association with a lipid having an
      asymmetric molecular geometry. The lipid considered in this study is
      mannosylerythritol lipid (MEL). MEL is specialized in having a unique molecular
      structure containing sugar alcohol erythritol as a hydrophilic part and two alkyl
      chains with different number of carbons as hydrophobic moieties. Our particular
      interest has been focused on experimentally demonstrating how MEL interacts with
      pseudo-ceramide molecules by observing phase properties, emulsion morphology, and
      suspension stability. The pseudo-ceramide emulsions prepared with MEL show
      remarkably improved dispersion stability without either formation of molecular
      crystals or changes in particle sizes even after storing them for a long time.
      This suggests that MEL readily associates with the pseudo-ceramide due to the
      hydrophobic interaction, while it makes a break in the continuity of the
      molecular assembly of the pseudo-ceramide molecules themselves due to the
      geometric hindrance coming from MEL's asymmetric molecular structure.

PMID- 24290100
TI  - "Frontal systems" behaviors in comorbid human immunodeficiency virus infection
      and methamphetamine dependency.
AB  - Human immunodeficiency virus (HIV) infection and methamphetamine (MA) dependence
      are associated with neural injury preferentially involving frontostriatal
      circuits. Little is known, however, about how these commonly comorbid conditions
      impact behavioral presentations typically associated with frontal systems
      dysfunction. Our sample comprised 47 HIV-uninfected/MA-nondependent; 25 HIV
      uninfected/MA-dependent; 36 HIV-infected/MA-nondependent; and 28 HIV-infected/MA
      dependent subjects. Participants completed self-report measures of "frontal
      systems" behaviors, including impulsivity/disinhibition, sensation-seeking, and
      apathy. They also underwent comprehensive neurocognitive and neuropsychiatric
      assessments that allowed for detailed characterization of neurocognitive deficits
      and comorbid/premorbid conditions, including lifetime Mood and Substance Use
      Disorders, Attention-Deficit/Hyperactivity Disorder, and Antisocial Personality
      Disorder. Multivariable regression models adjusting for potential confounds
      (i.e., demographics and comorbid/premorbid conditions) showed that MA dependence
      was independently associated with increased impulsivity/disinhibition, sensation
      seeking and apathy, and HIV infection with greater apathy. However, we did not
      see synergistic/additive effects of HIV and MA on frontal systems behaviors.
      Global neurocognitive impairment was relatively independent of the frontal
      systems behaviors, which is consistent with the view that these constructs may
      have relatively separable biopsychosocial underpinnings. Future research should
      explore whether both neurocognitive impairment and frontal systems behaviors may
      independently contribute to everyday functioning outcomes relevant to HIV and MA.

PMID- 24290104
TI  - Development of functional biointerfaces by surface modification of
      polydimethylsiloxane with bioactive chlorogenic acid.
AB  - The effect of physicochemical surface properties and chemical structure on the
      attachment and viability of bacteria and mammalian cells has been extensively
      studied for the development of biologically relevant applications. In this study,
      we report a new approach that uses chlorogenic acid (CA) to modify the surface
      wettability, anti-bacterial activity and cell adhesion properties of
      polydimethylsiloxane (PDMS). The chemical structure of the surface was obtained
      by X-ray photoelectron spectroscopy (XPS), the roughness was measured by atomic
      force microscopy (AFM), and the water contact angle was evaluated for PDMS
      substrates both before and after CA modification. Molecular modelling showed that
      the modification was predominately driven by van der Waals and electrostatic
      interactions. The exposed quinic-acid moiety improved the hydrophilicity of CA
      modified PDMS substrates. The adhesion and viability of E. coli and HeLa cells
      were investigated using fluorescence and phase contrast microscopy. Few viable
      bacterial cells were found on CA-coated PDMS surfaces compared with unmodified
      PDMS surfaces. Moreover, HeLa cells exhibited enhanced adhesion and increased
      spreading on the modified PDMS surface. Thus, CA-coated PDMS surfaces reduced the
      ratio of viable bacterial cells and increased the adhesion of HeLa cells. These
      results contribute to the purposeful design of anti-bacterial surfaces for
      medical device use.

PMID- 24290105
TI  - Medicine and its discontents.

PMID- 24290106
TI  - Optimizing the health of mothers, infants, and communities through research.

PMID- 24290107
TI  - Physical activity and cardiovascular risk: 10 metabolic equivalents or bust.

PMID- 24290108
TI  - The phantom limb of the triple aim.

PMID- 24290109
TI  - Physician satisfaction and burnout at different career stages.
AB  - OBJECTIVE: To explore the work lives, professional satisfaction, and burnout of
      US physicians by career stage and differences across sexes, specialties, and
      practice setting. PARTICIPANTS AND METHODS: We conducted a cross-sectional study
      that involved a large sample of US physicians from all specialty disciplines in
      June 2011. The survey included the Maslach Burnout Inventory and items that
      explored professional life and career satisfaction. Physicians who had been in
      practice 10 years or less, 11 to 20 years, and 21 years or more were considered
      to be in early, middle, and late career, respectively. RESULTS: Early career
      physicians had the lowest satisfaction with overall career choice (being a
      physician), the highest frequency of work-home conflicts, and the highest rates
      of depersonalization (all P<.001). Physicians in middle career worked more hours,
      took more overnight calls, had the lowest satisfaction with their specialty
      choice and their work-life balance, and had the highest rates of emotional
      exhaustion and burnout (all P<.001). Middle career physicians were most likely to
      plan to leave the practice of medicine for reasons other than retirement in the
      next 24 months (4.8%, 12.5%, and 5.2% for early, middle, and late career,
      respectively). The challenges of middle career were observed in both men and
      women and across specialties and practice types. CONCLUSION: Burnout,
      satisfaction, and other professional challenges for physicians vary by career
      stage. Middle career appears to be a particularly challenging time for
      physicians. Efforts to promote career satisfaction, reduce burnout, and
      facilitate retention need to be expanded beyond early career interventions and
      may need to be tailored by career stage.

PMID- 24290110
TI  - Maternal inactivity: 45-year trends in mothers' use of time.
AB  - OBJECTIVE: To examine 45-year trends in time use and physical activity energy
      expenditure (PAEE) in a nationally representative sample of US mothers.
      PARTICIPANTS AND METHODS: We quantified time allocation to physical activity
      (PA), sedentary behaviors (SED), and PAEE from 1965 to 2010 in mothers with older
      children (MOC) (>5 to <=18 years) and mothers with younger children (MYC) (<=5
      years). Physical activity was the sum of time allocated to housework, child care,
      laundry, food preparation, postmeal cleanup, and exercise. Sedentary behavior was
      the sum of time spent in a vehicle and using screen-based media. Physical
      activity energy expenditure was calculated using body weights from national
      surveys and metabolic equivalents. RESULTS: From 1965 to 2010, the time allocated
      to PA decreased by 11.1 h/wk (from 32.0 to 20.9 h/wk) in MOC and by 13.9 h/wk
      (from 43.6 to 29.7 h/wk) in MYC. The time spent in SED increased by 7.0 h/wk in
      MOC (from 17.7 to 24.7 h/wk) and increased by 5.7 h/wk in MYC (from 17.0 to 22.7
      h/wk). Physical activity energy expenditure decreased by 1237.6 kcal/wk (176.8
      kcal/d) in MOC (from 5835.3 to 4597.7 kcal/wk), and in MYC, PAEE decreased by
      1572.5 kcal/wk (224.6 kcal/d), from 7690.5 to 6118.0 kcal/wk. CONCLUSION: There
      was a significant reallocation of time by mothers from PA (eg, housework) to SED
      (eg, watching television) between 1965 and 2010. Given the essential role of PA
      for health and the potential for the intergenerational transmission of obesity
      and obesogenic behaviors, these results suggest that maternal inactivity may be
      an important target for the primary prevention of chronic noncommunicable
      diseases and obesity.

PMID- 24290111
TI  - Maternal vitamin D supplementation to improve the vitamin D status of breast-fed
      infants: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether a single monthly supplement is as effective as a
      daily maternal supplement in increasing breast milk vitamin D to achieve vitamin
      D sufficiency in their infants. PATIENTS AND METHODS: Forty mothers with
      exclusively breast-fed infants were randomized to receive oral cholecalciferol
      (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast
      milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was
      obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July
      29, 2011. RESULTS: In mothers given daily cholecalciferol, concentrations of
      serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL,
      respectively, from day 3 through 28. In mothers given the single dose, serum and
      breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1
      before rapidly declining. Maternal milk and serum cholecalciferol concentrations
      were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration
      increased from 17+/-13 to 39+/-6 ng/mL in the single-dose group and from 16+/-12
      to 39+/-12 ng/mL in the daily-dose group (P=.88). All infants achieved serum 25
      hydroxyvitamin D concentrations of more than 20 ng/mL. CONCLUSION: Either single
      dose or daily-dose cholecalciferol supplementation of mothers provided breast
      milk concentrations that result in vitamin D sufficiency in breast-fed infants.
      CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01240265.

PMID- 24290112
TI  - Supervised exercise-based intervention to prevent excessive gestational weight
      gain: a randomized controlled trial.
AB  - OBJECTIVE: To study the effect on maternal weight gain of a supervised light- to
      moderate-intensity exercise-based intervention performed from the ninth week of
      pregnancy. PARTICIPANTS AND METHODS: A total of 962 healthy pregnant women were
      randomly assigned to a standard care or exercise intervention group conducted
      between September 1, 2007, and January 31, 2011. The intervention included light-
      to moderate-intensity aerobic and resistance exercises performed 3 days a week
      (50-55 minutes per session). Excessive gestational weight gain was calculated on
      the basis of the 2009 Institute of Medicine (IOM) recommendations. Gestational
      body weight gain was calculated on the basis of the weight measured at the first
      prenatal visit (fifth to sixth weeks of gestation) and weight measured at the
      last visit to the clinic before delivery. Women were categorized into normal
      weight or overweight or obese. RESULTS: Women in the intervention group gained
      less weight (adjusted mean difference, 1.039 kg; 95% CI, 0.534-1.545 kg; P<.001)
      and were less likely to gain weight above the IOM recommendations (odds ratio,
      0.625; 95% CI, 0.461-0.847) compared with those in the standard care group. The
      main treatment effects according to body mass index category were that normal
      weight women in the intervention group gained less weight (adjusted mean
      difference, 1.393 kg; 95% CI, 0.813-1.972 kg; P<.001) and were less likely to
      gain weight above the IOM recommendations (odds ratio, 0.508; 95% CI, 0.334
      0.774) than normal weight women who received standard care. No significant
      treatment effect was observed in overweight or obese women. CONCLUSION:
      Supervised exercise of light to moderate intensity can be used to prevent
      excessive gestational weight gain, especially in normal weight women. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01790347.

PMID- 24290113
TI  - Validation of a novel protocol for calculating estimated energy requirements and
      average daily physical activity ratio for the US population: 2005-2006.
AB  - OBJECTIVE: To validate the PAR protocol, a novel method for calculating
      population-level estimated energy requirements (EERs) and average physical
      activity ratio (APAR), in a nationally representative sample of US adults.
      METHODS: Estimates of EER and APAR values were calculated via a factorial
      equation from a nationally representative sample of 2597 adults aged 20 and 74
      years (US National Health and Nutrition Examination Survey; data collected
      between January 1, 2005, and December 31, 2006). Validation of the PAR protocol
      derived EER (EER(PAR)) values was performed via comparison with values from the
      Institute of Medicine EER equations (EER(IOM)). RESULTS: The correlation between
      EER(PAR) and EER(IOM) was high (0.98; P<.001). The difference between EER(PAR)
      and EER(IOM) values ranged from 40 kcal/d (1.2% higher than EER(IOM)) in obese
      (body mass index [BMI] >=30) men to 148 kcal/d (5.7% higher) in obese women. The
      2005-2006 EERs for the US population were 2940 kcal/d for men and 2275 kcal/d for
      women and ranged from 3230 kcal/d in obese (BMI >=30) men to 2026 kcal/d in
      normal weight (BMI <25) women. There were significant inverse relationships
      between APAR and both obesity and age. For men and women, the APAR values were
      1.53 and 1.52, respectively. Obese men and women had lower APAR values than
      normal weight individuals (P1/4.023 and P1/4.015, respectively) [corrected], and
      younger individuals had higher APAR values than older individuals (P<.001).
      CONCLUSION: The PAR protocol is an accurate method for deriving nationally
      representative estimates of EER and APAR values. These descriptive data provide
      novel quantitative baseline values for future investigations into associations of
      physical activity and health.

PMID- 24290114
TI  - Characteristics and outcomes of patients who achieve high workload (>=10
      metabolic equivalents) during treadmill exercise echocardiography.
AB  - OBJECTIVE: To determine the frequency and prognostic significance of abnormal
      exercise echocardiographic results for patients achieving a workload of 10 or
      more metabolic equivalents during treadmill exercise echocardiography. PATIENTS
      AND METHODS: Patients who underwent treadmill exercise echocardiography from
      November 1, 2003, through December 31, 2008, and exercised for 9 or more minutes
      using the Bruce protocol (N=7236) were included. Clinical and exercise
      echocardiographic characteristics and outcomes were evaluated. Variables
      associated with abnormal exercise echocardiographic results and mortality were
      identified. RESULTS: Exercise echocardiographic results were positive for
      ischemia in 862 patients (12%). Extensive ischemia developed in 265 patients
      (4%). For patients with normal exercise echocardiographic results, all-cause and
      cardiovascular mortality rates were 0.30% and 0.05% per person-year of follow-up,
      respectively. For patients who had extensive ischemia, all-cause and
      cardiovascular mortality rates were 0.84% and 0.25% per person-year of follow-up,
      respectively. Patients at highest risk were those who had extensive and severe
      regional wall motion abnormalities at rest (n=58), and their all-cause and
      cardiovascular mortality rates were 2.65% and 0.76% per person-year of follow-up.
      Exercise echocardiographic variables did not identify sizable patient subgroups
      at risk for death and did not provide incremental prognostic information (C
      statistic was 0.74 compared with 0.73 for the clinical plus exercise
      electrocardiography model). CONCLUSION: Patients achieving a workload of 10 or
      more metabolic equivalents during treadmill exercise testing do not often have
      extensive ischemic abnormalities on exercise echocardiography. Although exercise
      echocardiographic results provide some prognostic information, it is not of
      incremental value for these patients, whose short-term and medium-term prognosis
      is excellent.

PMID- 24290116
TI  - Use of functional aerobic capacity based on stress testing to predict outcomes in
      normal, overweight, and obese patients.
AB  - OBJECTIVE: To determine the poorly studied relationship between functional
      aerobic capacity (FAC) as measured by treadmill stress testing and mortality in
      normal, overweight, and obese patients. PATIENTS AND METHODS: Patients were
      identified retrospectively from the stress testing database at Mayo Clinic in
      Rochester, Minnesota. We selected 5328 male nonsmokers (mean +/- SD age, 51.8+/
      11.5 years) without baseline cardiovascular disease who were referred for
      treadmill exercise testing between January 1, 1986, and December 31, 1991, and
      classified them by body mass index (BMI) into normal-weight (18.5-24.9 kg/m(2)),
      overweight (25.0-29.9 kg/m(2)), and obese (>=30 kg/m(2)) categories. Functional
      aerobic capacity was assessed by maximal exercise test results based on age- and
      sex-specific metabolic equivalents, and patients were stratified into fitness
      quintiles. Cox proportional hazards analysis was used to determine the
      relationship of all-cause mortality to fitness in each BMI category. RESULTS:
      There were 322 deaths during 14 years of follow-up. After adjustment for age and
      exercise confounders, FAC predicted mortality in the 3 BMI groups. Hazard ratios
      for FAC less than 80% of predicted vs a reference group with normal BMI and
      fitness (FAC >=100%) were 1.754 (95% CI, 0.874-3.522), 1.962 (1.356-2.837), and
      1.518 (1.056-2.182) for the normal, overweight, and obese groups, respectively.
      The CIs of the hazard ratios overlapped with no statistically significant
      differences (P>.05). CONCLUSION: A significant increase in mortality occurs with
      FAC below 80% of predicted for overweight and obese subjects and below 70% for
      normal weight subjects. Our results suggest that clinicians need not adjust the
      standard for low fitness in obese patients.

PMID- 24290117
TI  - Physical activity, quality of life, and burnout among physician trainees: the
      effect of a team-based, incentivized exercise program.
AB  - OBJECTIVE: To prospectively study the effects of an incentivized exercise program
      on physical activity (PA), quality of life (QOL), and burnout among residents and
      fellows (RFs) in a large academic medical center. PARTICIPANTS AND METHODS: In
      January 2011, all RFs at Mayo Clinic in Rochester, Minnesota (N=1060), were
      invited to participate in an elective, team-based, 12-week, incentivized exercise
      program. Both participants and nonparticipants had access to the same
      institutional exercise facilities. Regardless of participation, all RFs were
      invited to complete baseline and follow-up (3-month) assessments of PA, QOL, and
      burnout. RESULTS: Of the 628 RFs who completed the baseline survey (59%), only
      194 (31%) met the US Department of Health and Human Services recommendations for
      PA. Median reported QOL was 70 on a scale of 1 to 100, and 182 (29%) reported at
      least weekly burnout symptoms. A total of 245 individuals (23%) enrolled in the
      exercise program. No significant differences were found between program
      participants and nonparticipants with regard to baseline demographic
      characteristics, medical training level, PA, QOL, or burnout. At study
      completion, program participants were more likely than nonparticipants to meet
      the Department of Health and Human Services recommendations for exercise (48% vs
      23%; P<.001). Quality of life was higher in program participants than in
      nonparticipants (median, 75 vs 68; P<.001). Burnout was lower in participants
      than in nonparticipants, although the difference was not statistically
      significant (24% vs 29%; P=.17). CONCLUSION: A team-based, incentivized exercise
      program engaged 23% of RFs at our institution. After the program, participants
      had higher PA and QOL than nonparticipants who had equal exercise facility
      access. Residents and fellows may be much more sedentary than previously
      reported.

PMID- 24290115
TI  - Protective role of resting heart rate on all-cause and cardiovascular disease
      mortality.
AB  - OBJECTIVE: To study the protective role of lower resting heart rate (RHR) in
      cardiovascular disease (CVD) and all-cause mortality. PATIENTS AND METHODS:
      Patients (n=53,322) who received a baseline medical examination between January
      1, 1974, and December 31, 2002, were recruited from the Cooper Clinic, Dallas,
      Texas. They completed a medical questionnaire and underwent clinical evaluation.
      Patients with CVD or cancer or who had less than 1 year of mortality follow-up
      were excluded from the study. Relative risks and 95% CIs for all-cause and CVD
      mortality across RHR categories were estimated using Cox proportional hazards
      models. RESULTS: Highest cardiorespiratory fitness with lower mortality was found
      in individuals with an RHR of less than 60 beats/min. Similarly, patients with a
      higher RHR (>=80 beats/min) were at greater risk for CVD and all-cause mortality
      compared with an RHR of less than 60 beats/min. This analysis was followed by
      stratification of the data by hypertension, where hypertensive individuals with
      high RHRs (>=80 beats/min) were found to be at greater risk for CVD and all-cause
      mortality compared with those with hypertension and lower RHRs (<60 beats/min).
      In addition, unfit individuals with high RHRs had the greatest risk of CVD and
      all-cause mortality. The unfit with low RHR group had a similar risk for CVD and
      all-cause mortality as the fit with high RHR group. CONCLUSION: Lower
      cardiorespiratory fitness levels and higher RHRs are linked to greater CVD and
      all-cause mortality.

PMID- 24290118
TI  - Increasing the dose of varenicline in patients who do not respond to the standard
      dose.
AB  - Varenicline is a partial agonist of alpha4beta2 nicotinic acetylcholine
      receptors. It is effective at dosages of 2 mg/d for 12 weeks, but not for all
      smokers. It is possible that increasing the dose can increase the drug efficacy.
      We reviewed the clinical records of consecutive smokers who had been treated in 2
      smoking cessation services with varenicline at doses of 3 mg/d. In all cases, the
      treatment program consisted of a combination of behavioral therapy and drug
      treatment. Varenicline was prescribed at a standard dosage for 8 weeks. After 8
      weeks of treatment, the dose was increased to 3 mg/d if patients tolerated
      varenicline well and continued smoking or, in spite of not smoking, if they
      experienced severe withdrawal symptoms. The sample included 73 patients, of whom
      52 continued to smoke at 8 weeks and 21 stopped smoking but reported severe
      withdrawal discomfort. Carbon monoxide-validated continuous abstinence rates from
      week 9 to week 24 were 40% and 48% in these 2 subgroups, respectively. The
      increase in dosage was associated with adverse events in 22 patients (30%). These
      were mostly mild and included nausea, vomiting, abnormal dreams, and insomnia.
      Only 2 patients discontinued treatment (both because of nausea and vomiting).
      Thus, we conclude that increasing the varenicline dose in smokers who do not
      respond to the standard dose after 8 weeks of treatment is associated with
      limited adverse events and high success rates. 

PMID- 24290120
TI  - The epidemiology of skin and skin-related diseases: a review of population-based
      studies performed by using the Rochester Epidemiology Project.
AB  - In Olmsted County, Minnesota, population-based epidemiologic research studies are
      possible because of a unique medical records linkage system, the Rochester
      Epidemiology Project (REP), which has been in place for almost half a century. We
      present a summary of epidemiologic data describing the incidence of skin diseases
      derived from the REP. Since 1966, more than 2000 articles have been published by
      the REP team. Each published article was reviewed by both authors in conjunction
      with the REP team to select all articles that described the incidence of skin and
      selected skin-related diseases. Collectively, these reports suggested that the
      incidence of most of the studied skin diseases has increased over the decades. 

PMID- 24290119
TI  - Physical activity promotion in the health care system.
AB  - Physical activity (PA) and exercise training (ET) have great potential in the
      prevention, management, and rehabilitation of a variety of diseases, but this
      potential has not been fully realized in clinical practice. The health care
      system (HCS) could do much more to support patients in increasing their PA and
      ET. However, counseling on ET is not used widely by the HCS owing partly to
      attitudes but mainly to practical obstacles. Extensive searches of MEDLINE, the
      Cochrane Library, the Database of Abstracts of Reviews of Effects, and
      ScienceDirect for literature published between January 1, 2000, and January 31,
      2013, provided data to assess the critical characteristics of ET counseling. The
      evidence reveals that especially brief ET counseling is an efficient, effective,
      and cost-effective means to increase PA and ET and to bring considerable clinical
      benefits to various patient groups. Furthermore, it can be practiced as part of
      the routine work of the HCS. However, there is a need and feasible means to
      increase the use and improve the quality of ET counseling. To include PA and ET
      promotion as important means of comprehensive health care and disease management,
      a fundamental change is needed. Because exercise is medicine, it should be seen
      and dealt with in the same ways as pharmaceuticals and other medical
      interventions regarding the basic and continuing education and training of health
      care personnel and processes to assess its needs and to prescribe and deliver it,
      to reimburse the services related to it, and to fund research on its efficacy,
      effectiveness, feasibility, and interactions and comparability with other
      preventive, therapeutic, and rehabilitative modalities. This change requires
      credible, strong, and skillful advocacy inside the medical community and the HCS.

PMID- 24290121
TI  - Human immunodeficiency virus: what primary care clinicians need to know.
AB  - Human immunodeficiency virus (HIV) has evolved from an illness that consistently
      led to death to a chronic disease that can be medically managed. Primary care
      clinicians can provide beneficial care to the individual patient and potentially
      decrease the transmission of HIV to others through appropriate HIV screening and
      recognition of clinical clues to both chronic and acute HIV. Most patients who
      take combination antiretroviral therapy experience immune reconstitution and
      resume normal lives. These patients benefit from the care of an experienced
      primary care clinician in addition to a clinician with HIV expertise. Primary
      care clinicians have expertise providing preventive care, including counseling
      regarding healthier lifestyle choices and managing cardiovascular risk factors,
      osteoporosis, hypertension, and diabetes, all of which have become increasingly
      important for individuals with HIV as they age. This article reviews the many
      important roles of primary care clinicians with regard to the HIV epidemic and
      care of patients with HIV. 

PMID- 24290122
TI  - 69-year-old woman with ascites, hypoxia, and weight loss.

PMID- 24290123
TI  - Regenerative nanomedicine for vision restoration.
AB  - Herein, we discuss recent applications of nanotechnology to ophthalmology,
      including nanoparticles for drug, gene, and trophic factor delivery; regenerative
      medicine (in the areas of optogenetics and optic nerve regeneration); and
      diagnostics (eg, minimally invasive biometric monitoring). Specific applications
      for the management of choroidal neovascularization, retinal neovascularization,
      oxidative damage, optic nerve damage, and retinal degenerative disease are
      considered. Nanotechnology will play an important role in early- and late-stage
      interventions in the management of blinding diseases. 

PMID- 24290124
TI  - Factors affecting the association of coffee consumption with all-cause and
      cardiovascular disease mortality.

PMID- 24290125
TI  - Coffee consumption and all-cause mortality: it may be premature to advise
      limiting coffee consumption in younger nonsmokers.

PMID- 24290126
TI  - Heavy coffee drinking and age-dependent all-cause mortality.

PMID- 24290127
TI  - Importance of sleep disorders in assessing the association between coffee
      consumption and all-cause mortality.

PMID- 24290128
TI  - In reply--Association of coffee consumption with all-cause and cardiovascular
      disease mortality.

PMID- 24290129
TI  - 23-year-old man with fever and a sore thumb.

PMID- 24290130
TI  - Absent response of intracranial melanoma metastases harboring BRAF V600E sequence
      variation to vemurafenib.

PMID- 24290131
TI  - Seeing is not always believing: congenital insensitivity to pain with anhidrosis
      mimicking leprosy.

PMID- 24290132
TI  - Alois Alzheimer--Alzheimer disease.

PMID- 24290134
TI  - Quantification of photocatalytic oxygenation of human blood.
AB  - Photocatalytic oxygenation of human blood is an emerging concept based on the
      principle of photocatalytic splitting of water into oxygen and hydrogen. This
      communication reports: (i) a design of a photocatalytic cell (PC) that separates
      the blood from UV (incident) radiation source, (ii) a pH, temperature and flow
      controlled circuit designed for quantifying the oxygenation of human blood by
      photocatalysis and (iii) measuring the current efficacy of ITO/TiO2 nano thin
      films in oxygenating human blood in a dynamic circuit in real time. The average
      increase in oxygen saturation was around 5% above baseline compared to control
      (p<0.0005). We believe this is one of the first attempts to quantify
      photocatalytic oxygenation of human blood under controlled conditions. 

PMID- 24290135
TI  - A novel methodology for generating 3D finite element models of the hip from 2D
      radiographs.
AB  - Finite element (FE) modelling has been proposed as a tool for estimating fracture
      risk and patient-specific FE models are commonly based on computed tomography
      (CT). Here, we present a novel method to automatically create personalised 3D
      models from standard 2D hip radiographs. A set of geometrical parameters of the
      femur were determined from seven a-p hip radiographs and compared to the 3D
      femoral shape obtained from CT as training material; the error in reconstructing
      the 3D model from the 2D radiographs was assessed. Using the geometry parameters
      as the input, the 3D shape of another 21 femora was built and meshed, separating
      a cortical and trabecular compartment. The material properties were derived from
      the homogeneity index assessed by texture analysis of the radiographs, with focus
      on the principal tensile and compressive trabecular systems. The ability of these
      FE models to predict failure load as determined by experimental biomechanical
      testing was evaluated and compared to the predictive ability of DXA. The average
      reconstruction error of the 3D models was 1.77 mm (+/-1.17 mm), with the error
      being smallest in the femoral head and neck, and greatest in the trochanter. The
      correlation of the FE predicted failure load with the experimental failure load
      was r(2)=64% for the reconstruction FE model, which was significantly better
      (p<0.05) than that for DXA (r(2)=24%). This novel method for automatically
      constructing a patient-specific 3D finite element model from standard 2D
      radiographs shows encouraging results in estimating patient-specific failure
      loads.

PMID- 24290136
TI  - Descending aorta subject-specific one-dimensional model validated against in vivo
      data.
AB  - The aorta plays a major role in the cardiovascular system and its function and
      structure are primarily affected by aging, eating habits, life style and other
      cardiovascular risk factors, inducing increased stiffness which is associated
      with cardiovascular and cerebral morbi-mortality. Our objective was to develop
      and validate a robust subject-specific one-dimensional wave propagation numerical
      model of the descending aorta. This model with a cross-sectional area, velocity
      and pressure formulation is built using geometric and hemodynamic data measured
      on a specific person and is validated against in vivo data acquired on the same
      subject at three distinct anatomical locations along the thoracic aorta. We
      studied seven healthy volunteers, who underwent carotid applanation tonometry and
      aortic cardiovascular magnetic resonance (CMR). Responses of our model in terms
      of changes in central pressure waveform with arterial alterations were consistent
      with previously described physiological knowledge. Quantitative validation
      averaged over the three descending aortic locations and the seven subjects
      provided low rms errors (given in percentage of the maximal clinical value)
      between simulated and CMR data, i.e. area: 10+/-6%, velocity: 11+/-3%, flow rate:
      9+/-3%. Finally, we also found low rms (5+/-2%) when comparing simulated pressure
      in the proximal aortic location against tonometric carotid pressure curves. In
      conclusion, this simple model performs similar to more complex models of the
      entire systemic arterial tree at a fraction of the cost, and could be of major
      usefulness in the non-invasive and local estimation of proximal biomechanical and
      hemodynamic indices. 

PMID- 24290137
TI  - Biomechanical properties of native and tissue engineered heart valve constructs.
AB  - Due to the increasing number of heart valve diseases, there is an urgent clinical
      need for off-the-shelf tissue engineered heart valves. While significant progress
      has been made toward improving the design and performance of both mechanical and
      tissue engineered heart valves (TEHVs), a human implantable, functional, and
      viable TEHV has remained elusive. In animal studies so far, the implanted TEHVs
      have failed to survive more than a few months after transplantation due to
      insufficient mechanical properties. Therefore, the success of future heart valve
      tissue engineering approaches depends on the ability of the TEHV to mimic and
      maintain the functional and mechanical properties of the native heart valves.
      However, aside from some tensile quasistatic data and flexural or bending
      properties, detailed mechanical properties such as dynamic fatigue, creep
      behavior, and viscoelastic properties of heart valves are still poorly
      understood. The need for better understanding and more detailed characterization
      of mechanical properties of tissue engineered, as well as native heart valve
      constructs is thus evident. In the current review we aim to present an overview
      of the current understanding of the mechanical properties of human and common
      animal model heart valves. The relevant data on both native and tissue engineered
      heart valve constructs have been compiled and analyzed to help in defining the
      target ranges for mechanical properties of TEHV constructs, particularly for the
      aortic and the pulmonary valves. We conclude with a summary of perspectives on
      the future work on better understanding of the mechanical properties of TEHV
      constructs. 

PMID- 24290138
TI  - Changes in the interfacial shear resistance of disc annulus fibrosus from genipin
      crosslinking.
AB  - Crosslinking soft tissue has become more common in tissue engineering
      applications, and recent studies have demonstrated that soft tissue mechanical
      behavior can be directly altered through crosslinking. Using a recently reported
      test method that shears adjacent disc lamella, the effect of genipin crosslinking
      on interlamellar shear resistance was studied using in vitro bovine disc annulus.
      Specimens of adjacent lamella were dissected from four discs taken from three
      fresh frozen bovine tails. These specimens were paired and soaked in either 50 mM
      EPPS Phosphate (ph9) with 20 mM genipin at 37  degrees C for 4 h or in 50 mM EPPS
      Phosphate (ph9) of which twelve specimens (6 per treatment) were successfully
      tested and analyzed. Crosslinked specimens were noted to have significantly
      higher yield force per width (59%), peak force per width (70%), and resilience
      (69%) compared to sham treated controls, supporting the hypothesis that genipin
      crosslinking increases the resistance to interlamellar shear of the annulus
      interface. Additionally, a possible dependency may exist between the
      interlamellar shear strength and neighboring lamella because of the bridging
      fiber network previously described by other investigators.

PMID- 24290139
TI  - Atomic force microscopy to investigate spatial patterns of response to
      interleukin-1beta in engineered cartilage tissue elasticity.
AB  - Atomic force microscopy (AFM) has been proposed as a tool to evaluate the
      structural and mechanical properties of cartilage tissue. Here, we aimed at
      assessing whether AFM can be employed to quantify spatially resolved elastic
      response of tissue engineered cartilage (TEC) to short exposure to IL-1beta, thus
      mimicking the initially inflammatory implantation site. TEC generated by 14 days
      of pellet-culture of expanded human chondrocytes was left untreated (ctr) or
      exposed to IL-1beta for 3 days. TEC pellets were then cut in halves that were
      glued on a Petri dish. Profiles of elasticity were obtained by sampling with a
      nanometer sized, pyramidal indenting tip, with 200um step resolution, the freshly
      exposed surfaces along selected directions. Replicate TECs were analyzed
      biochemically and histologically. GAG contents and elasticity of pellets
      decreased (1.4- and 2.6-fold, respectively, p<0.05) following IL-1beta
      stimulation. Tissue quality was evaluated by scoring histological pictures taken
      at 200MUm intervals, using the Bern-score grading system. At each distance,
      scores of ctr TEC were higher than those IL-1beta treated, with the largest
      differences between the two groups observed in the central regions. Consistent
      with the histological results, elasticity of IL-1beta-treated TEC was lower than
      in ctr pellets (up to 3.4-fold at 200MUm from the center). IL-1beta treated but
      not ctr TEC was intensely stained for MMP-13 and DIPEN (cryptic fragment of
      aggrecan) especially in the central regions. The findings indicate the potential
      of AFM to investigate structure/function relationships in TEC and to perform
      tests aimed at predicting the functionality of TEC upon implantation. 

PMID- 24290140
TI  - Structure and function of the CSL-KyoT2 corepressor complex: a negative regulator
      of Notch signaling.
AB  - Notch refers to a highly conserved cell-to-cell signaling pathway with essential
      roles in embryonic development and tissue maintenance. Dysfunctional signaling
      causes human disease, highlighting the importance of pathway regulation. Notch
      signaling ultimately results in the activation of target genes, which is
      regulated by the nuclear effector CSL (CBF-1/RBP-J, Su(H), Lag-1). CSL dually
      functions as an activator and a repressor of transcription through differential
      interactions with coactivator or corepressor proteins, respectively. Although the
      structures of CSL-coactivator complexes have been determined, the structures of
      CSL-corepressor complexes are unknown. Here, using a combination of structural,
      biophysical, and cellular approaches, we characterize the structure and function
      of CSL in complex with the corepressor KyoT2. Collectively, our studies provide
      molecular insights into how KyoT2 binds CSL with high affinity and competes with
      coactivators, such as Notch, for binding CSL. These studies are important for
      understanding how CSL functions as both an activator and a repressor of
      transcription of Notch target genes. 

PMID- 24290141
TI  - Structural basis of the autophagy-related LC3/Atg13 LIR complex: recognition and
      interaction mechanism.
AB  - Autophagy is a bulk degradation pathway that removes cytosolic materials to
      maintain cellular homeostasis. The autophagy-related gene 13 (Atg13) and
      microtubule associate protein 1 light chain 3 (LC3) proteins are required for
      autophagosome formation. We demonstrate that each of the human LC3 isoforms
      (LC3A, LC3B, and LC3C) interacts with Atg13 via the LC3 interacting region (LIR)
      of Atg13. Using X-ray crystallography, we solved the macromolecular structures of
      LC3A and LC3C, along with the complex structures of the LC3 isoforms with the
      Atg13 LIR. Together, our structural and binding analyses reveal that the side
      chain of Lys49 of LC3 acts as a gatekeeper to regulate binding of the LIR. We
      verified this observation by mutation of Lys49 in LC3A, which significantly
      reduces LC3A positive puncta formation in cultured cells. Our results suggest
      that specific affinity of the LC3 isoforms to the Atg13 LIR is required for
      proper autophagosome formation. 

PMID- 24290142
TI  - Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary
      tumor and pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor.
      Little data are available on positron emission tomographic/computed tomographic
      (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic
      characteristics of SPT using F-18-FDG PET/CT and compared the results with those
      of pancreatic ductal adenocarcinoma. METHODS: We retrospectively reviewed the
      records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT
      patients had primary tumors and 1 patient had metastatic SPT. Maximum
      standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV),
      total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were
      evaluated. Mann-Whitney U test between pancreatic SPT and ductal adenocarcinoma
      was performed. In addition, age, gender and tumor size-adjusted analysis of
      covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma.
      RESULTS: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly
      higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly
      correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver
      and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and
      after PET/CT had suggested the presence of pancreatic SPT. CONCLUSION: We
      recommend that SPT be considered when a solid pancreatic mass with increased FDG
      metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting
      subtle metastases of SPT.

PMID- 24290143
TI  - Changing monsoon patterns, snow and glacial melt, its impacts and adaptation
      options in northern India: synthesis.
AB  - This paper gives a synthesis of this special issue on the sensitivity to climate
      change of the main bio-physical processes in the Hindukush-Karakoram-Himalayas.
      It also describes the impacts on the water resources with a special focus on the
      Ganges. Consequences of changes in water resources and possible adaptation
      measures for different sectors are discussed. 

PMID- 24290144
TI  - Soundscape in the sustainable living environment: A cross-cultural comparison
      between the UK and Taiwan.
AB  - This study examines the effects of cultural factors on the evaluation of acoustic
      quality of residential areas, within the context of general environmental
      conditions. A comparative study was carried out between the UK and Taiwan,
      through questionnaire surveys at three stages, namely in selected residential
      areas, with respondents in their place of work/study, and using a web-based
      survey, respectively. This study reveals the importance of considering cultural
      factors, as well as their living experiences. This is reflected by the
      significant differences between the two cultures in a number of aspects,
      including choosing and evaluating living environment, noise noticeability,
      annoyance and sleep disturbance, activities, and sound preference. It is
      interesting to note the factor 'quiet' is an important consideration compared to
      other factors, in both the UK and Taiwan. 

PMID- 24290145
TI  - Application of stochastic approach based on Monte Carlo (MC) simulation for life
      cycle inventory (LCI) to the steel process chain: case study.
AB  - The purpose of the paper is to present the results of application of stochastic
      approach based on Monte Carlo (MC) simulation for life cycle inventory (LCI) data
      of Mittal Steel Poland (MSP) complex in Krakow, Poland. In order to assess the
      uncertainty, the software CrystalBall(r) (CB), which is associated with
      Microsoft(r) Excel spreadsheet model, is used. The framework of the study was
      originally carried out for 2005. The total production of steel, coke, pig iron,
      sinter, slabs from continuous steel casting (CSC), sheets from hot rolling mill
      (HRM) and blast furnace gas, collected in 2005 from MSP was analyzed and used for
      MC simulation of the LCI model. In order to describe random nature of all main
      products used in this study, normal distribution has been applied. The results of
      the simulation (10,000 trials) performed with the use of CB consist of frequency
      charts and statistical reports. The results of this study can be used as the
      first step in performing a full LCA analysis in the steel industry. Further, it
      is concluded that the stochastic approach is a powerful method for quantifying
      parameter uncertainty in LCA/LCI studies and it can be applied to any steel
      industry. The results obtained from this study can help practitioners and
      decision-makers in the steel production management. 

PMID- 24290146
TI  - Tempo effects may distort the interpretation of trends in life expectancy.
AB  - OBJECTIVES: Recently, a new interpretation problem of trends in period life
      expectancy has been discussed in the demographic literature. The so-called tempo
      effects arise if large numbers of deaths are suddenly postponed. In such
      conditions, the life table inflates longevity gains in the population because it
      weights avoided deaths with the full remaining life expectancy. This article
      explains how such effects occur and indicates their relevance using an
      illustrative example. STUDY DESIGN AND SETTING: Data of East and West Germany
      from the Human Mortality Database for the years 1990-2009 were used. We simulated
      a scenario that contrasts the observed life expectancy in West and East Germany
      with an alternative one based on the assumption of short-term postponements of
      deaths. RESULTS: Our example demonstrates that if tempo effects have distorted
      changes in life expectancy, the pace of improvement in underlying mortality
      conditions could be over- and underestimated. CONCLUSION: We recommend that the
      assumptions of the life table, in this case about the remaining life expectancy
      of avoided deaths, are carefully evaluated in all applications. Interdisciplinary
      efforts to develop models to detect and quantify tempo effects from life
      expectancy calculations should be put on the research agenda.

PMID- 24290147
TI  - Adjudication-related processes are underreported and lack standardization in
      clinical trials of venous thromboembolism: a systematic review.
AB  - OBJECTIVES: Although the use of an adjudication committee (AC) for outcomes is
      recommended in randomized controlled trials, there are limited data on the
      process of adjudication. We therefore aimed to assess whether the reporting of
      the adjudication process in venous thromboembolism (VTE) trials meets existing
      quality standards and which characteristics of trials influence the use of an AC.
      STUDY DESIGN AND SETTING: We systematically searched MEDLINE and the Cochrane
      Library from January 1, 2003, to June 1, 2012, for randomized controlled trials
      on VTE. We abstracted information about characteristics and quality of trials and
      reporting of adjudication processes. We used stepwise backward logistic
      regression model to identify trial characteristics independently associated with
      the use of an AC. RESULTS: We included 161 trials. Of these, 68.9% (111 of 161)
      reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used
      independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication
      decision was reached within the AC, and 4.5% (5 of 111) reported on whether the
      reliability of adjudication was assessed. In multivariate analyses, multicenter
      trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a
      data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary
      outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC.
      Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open
      label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC.
      CONCLUSION: Recommended processes of adjudication are underreported and lack
      standardization in VTE-related clinical trials. The use of an AC varies
      substantially by trial characteristics.

PMID- 24290148
TI  - Reducing questionnaire length did not improve physician response rate: a
      randomized trial.
AB  - OBJECTIVES: To examine the effect of reducing questionnaire length on the
      response rate in a physician survey. STUDY DESIGN AND SETTING: A postal four
      double-page questionnaire on end-of-life decision making was sent to a random
      sample of 1,100 general practitioners, 400 elderly care physicians, and 500
      medical specialists. Another random sample of 500 medical specialists received a
      shorter questionnaire of two double pages. After 3 months and one reminder, all
      nonresponding physicians received an even shorter questionnaire of one double
      page. RESULTS: Total response was 64% (1,456 of 2,269 eligible respondents).
      Response rate of medical specialists for the four double-page questionnaire was
      equal to that of the two double-page questionnaire (190 and 191 questionnaires
      were returned, respectively). The total response rate increased from 53% to 64%
      after sending a short one double-page questionnaire (1,203-1,456 respondents).
      CONCLUSION: The results of our study suggest that reducing the length of a long
      questionnaire in a physician survey does not necessarily improve response rate.
      To improve response rate and gather more information, researchers could decide to
      send a drastically shortened version of the questionnaire to nonresponders.

PMID- 24290149
TI  - Response to van den Bruel and Perera: the comprehensive diagnostic study: a new
      solution to old problems?

PMID- 24290150
TI  - The comprehensive diagnostic study is suggested as a design to model the
      diagnostic process.
AB  - OBJECTIVES: The classical diagnostic cross-sectional study has a focus on one
      disease only. Generalist clinicians, however, are confronted with a wide range of
      diagnoses. We propose the "comprehensive diagnostic study design" to evaluate
      diagnostic tests regarding more than one disease outcome. STUDY DESIGN AND
      SETTING: We present the secondary analysis of a data set obtained from patients
      presenting with chest pain in primary care. Participating clinicians recorded 42
      items of the history and physical examination. Diagnostic outcomes were reviewed
      by an independent panel after 6-month follow-up (n = 710 complete cases). We used
      Shannon entropy as a measure of uncertainty before and after testing. Four
      different analytical strategies modeling specific clinical ways of reasoning were
      evaluated. RESULTS: Although the "global entropy" strategy reduced entropy most,
      it is unlikely to be of clinical use because of its complexity. "Inductive" and
      "fixed-set" strategies turned out to be efficient requiring a small amount of
      data only. The "deductive" procedure resulted in the smallest reduction of
      entropy. CONCLUSION: We suggest that the comprehensive diagnostic study design is
      a feasible and valid option to improve our understanding of the diagnostic
      process. It is also promising as a justification for clinical recommendations.

PMID- 24290151
TI  - The comprehensive diagnostic study: a new solution to old problems?

PMID- 24290152
TI  - [Usefulness of procalcitonin for prescribing of antibiotics and suspicion of
      bacteremia in the emergency department].

PMID- 24290153
TI  - [Acute renal damage due to N-acetyl-sulphadiazine crystals. An avoidable
      complication?].

PMID- 24290154
TI  - [Follow-up of newborns with hypoxic-ischaemic encephalopathy].
AB  - Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy
      reduces the number of neonates who die or have permanent neurological deficits.
      Although this therapy is now standard of care, neonatal hypoxic-ischaemic
      encephalopathy still has a significant impact on the child's neurodevelopment and
      quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled
      in multidisciplinary follow-up programs in order to detect impairments, to
      initiate early intervention, and to provide counselling and support for families.
      This article describes the main neurodevelopmental outcomes after term neonatal
      hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on
      the infant's clinical condition and other prognostic indicators, mainly neonatal
      neuroimaging. Other aspects, such as palliative care and medico-legal issues, are
      also briefly discussed. 

PMID- 24290155
TI  - [Heat stroke related to the use of topiramate. The importance of prevention].
AB  - Heat stroke is the most severe pathology related to heat. It is defined as an
      increase in core body temperature accompanied by signs of neurological
      dysfunction. In the absence of an early treatment, it has a very high mortality
      rate. Topiramate is a well known drug widely used in epilepsy treatment and
      migraine prevention. Oligohydrosis has been described amongst topiramate side
      effects, favouring the risk of hyperthermia and heatstroke. We present the case
      of a patient who developed heat stroke due to physical exercise while under
      topiramate treatment. 

PMID- 24290156
TI  - [Amyoplasia congenita].

PMID- 24290157
TI  - [Do we believe our recommendations on vitamin D in infants?].

PMID- 24290158
TI  - Imaging apathy in Alzheimer's disease.

PMID- 24290159
TI  - Development of the PHASES score for prediction of risk of rupture of intracranial
      aneurysms: a pooled analysis of six prospective cohort studies.
AB  - BACKGROUND: The decision of whether to treat incidental intracranial saccular
      aneurysms is complicated by limitations in current knowledge of their natural
      history. We combined individual patient data from prospective cohort studies to
      determine predictors of aneurysm rupture and to construct a risk prediction chart
      to estimate 5-year aneurysm rupture risk by risk factor status. METHODS: We did a
      systematic review and pooled analysis of individual patient data from 8382
      participants in six prospective cohort studies with subarachnoid haemorrhage as
      outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and
      assessed predictors with Cox proportional-hazard regression analysis. FINDINGS:
      Rupture occurred in 230 patients during 29,166 person-years of follow-up. The
      mean observed 1-year risk of aneurysm rupture was 1.4% (95% CI 1.1-1.6) and the 5
      year risk was 3.4% (2.9-4.0). Predictors were age, hypertension, history of
      subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical
      region. In study populations from North America and European countries other than
      Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0.25%
      in individuals younger than 70 years without vascular risk factors with a small
      sized (<7 mm) internal carotid artery aneurysm, to more than 15% in patients aged
      70 years or older with hypertension, a history of subarachnoid haemorrhage, and a
      giant-sized (>20 mm) posterior circulation aneurysm. By comparison with
      populations from North America and European countries other than Finland, Finnish
      people had a 3.6-times increased risk of aneurysm rupture and Japanese people a
      2.8-times increased risk. INTERPRETATION: The PHASES score is an easily
      applicable aid for prediction of the risk of rupture of incidental intracranial
      aneurysms. FUNDING: Netherlands Organisation for Health Research and Development.

PMID- 24290160
TI  - Intracranial aneurysms: individualising the risk of rupture.

PMID- 24290161
TI  - Controversial Liverpool care pathway withdrawn in the United Kingdom after
      official government review.

PMID- 24290162
TI  - Health-related quality of life in Swedish pediatric burn patients and
      associations with burn and family characteristics.
AB  - Although many children with burns recover well and have a satisfying quality of
      life after the burn, some children do not adjust as well. Health-related quality
      of life (HRQoL) focuses on the impact health status has on quality of life. The
      aim of this study was to assess HRQoL with the American Burn Association/Shriners
      Hospitals for Children Burn Outcomes Questionnaire (BOQ) in a nationwide Swedish
      sample of children with burns 0.3-9.0 years after injury. Participants were
      parents (n=109) of children aged up to 18 years at the time of investigation who
      were treated at the Linkoping or Uppsala Burn Center between 2000 and 2008. The
      majority of children did not have limitations in physical function and they did
      not seem to experience much pain. However, there were indications of psychosocial
      problems. Parents of preschool children reported most problems with the
      children's behavior and family disruption, whereas parents of children aged 5-18
      years reported most problems with appearance and emotional health. There were
      mainly burn-related variables associated with suboptimal HRQoL in children aged 5
      18 years, while family-related variables did not contribute as much. 

PMID- 24290163
TI  - Higher consumption of sugar-sweetened soft drinks increases the risk of
      hyperuricemia in Korean population: The Korean Multi-Rural Communities Cohort
      Study.
AB  - OBJECTIVE: The clinical implication of sugar-sweetened soft drinks on the risk of
      hyperuricemia has increased, especially in Western population studies. The aim of
      this study is to clarify the association between sugar-sweetened soft drinks and
      fruit drinks made from oranges and apples and the risk of hyperuricemia in the
      Korean Multi-Rural Communities Cohort. METHODS: A total of 9400 subjects were
      enrolled in the Korean Multi-Rural Communities Cohort Study, and a cross
      sectional analysis was performed. Five quintiles (Q1-Q5) according to consumption
      of soft drinks and other fruit/fruit juices were classified and then categorized
      into three groups (Q1-Q3, Q4, and Q5) to assess the risk of hyperuricemia.
      Information on dietary intake was collected by well-trained interviewers using
      validated food frequency questionnaires. RESULTS: Higher consumption of sugar
      sweetened soft drinks (Q5) increased the risk of hyperuricemia in males (adjusted
      OR = 1.35, 95% CI: 1.07-1.71) with a linear trend (p for trend = 0.01) and in
      females (adjusted OR = 1.40, 95% CI: 1.03-1.90) with no linear trend (p for trend
      = 0.09), compared to lower consumption (Q1-Q3). However, there were no
      significant differences of serum uric acid level according to the three
      categories of soft drink consumption, Q1-Q3, Q3, and Q5, in males (p = 0.21) or
      in females (p = 0.16), whereas all subjects showed statistical significance of
      serum uric acid level within the categories (p < 0.001). Estimated amount of soft
      drink intake was associated with serum uric acid level in males (beta = 0.001; p
      = 0.01) but not in females (beta = 0.0005; p = 0.10). CONCLUSION: Higher
      consumption of sugar-sweetened soft drinks increased the risk of hyperuricemia in
      the Korean population, showing a differential linear trend for hyperuricemia
      according to gender.

PMID- 24290164
TI  - Colistimethate sodium powder and tobramycin powder for inhalation for the
      treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis:
      systematic review and economic model.
AB  - BACKGROUND: Cystic fibrosis (CF) is an inherited condition characterised by the
      abnormal transport of chloride ions across transporting epithelia. This leads to
      the production of thick sticky mucus in the lungs, pancreas, liver, intestine and
      reproductive tract, and an increase in the salt content in sweat. Among other
      problems, people with CF experience recurrent respiratory infections and have
      difficulties digesting food. CF affects over 9000 individuals in the UK. CF
      shortens life expectancy and adversely affects quality of life. In 2010, CF was
      recorded as the cause of 103 deaths in England and Wales. OBJECTIVE: To evaluate
      the clinical effectiveness and cost-effectiveness of colistimethate sodium dry
      powder for inhalation (DPI) (Colobreathe((r)), Forest Laboratories) and
      tobramycin DPI (TOBI Podhaler((r)), Novartis Pharmaceuticals) for the treatment
      of Pseudomonas aeruginosa lung infection in CF. DATA SOURCES: Electronic
      databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process &
      Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), Web of Science,
      Conference Proceedings Citation Index (CPCI) and Bioscience Information Service
      (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished
      studies, and bibliographies of relevant systematic reviews and the manufacturers'
      submissions were also hand-searched. REVIEW METHODS: A systematic review of the
      clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and
      tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF
      was conducted. Existing economic evidence within the literature was reviewed and
      a de novo health economic model was also developed. RESULTS: Three randomised
      controlled trials (RCTs) were included in the clinical effectiveness review. Both
      colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to
      nebulised tobramycin for the outcome forced expiratory volume in first second
      percentage predicted (FEV1%). It was not possible to draw any firm conclusions as
      to the relative efficacy of colistimethate sodium DPI compared with tobramycin
      DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer
      quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the
      incremental discounted lifetime cost of tobramycin DPI compared with nebulised
      tobramycin, it highly unlikely that tobramycin DPI has an incremental cost
      effectiveness ratio that is better than L30,000 per QALY gained. LIMITATION: The
      uncertainty surrounding the short-term evidence base inevitably results in
      uncertainty surrounding the long-term clinical effectiveness and cost
      effectiveness of colistimethate sodium DPI. CONCLUSIONS: Both DPI formulations
      have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%.
      The results of these trials should be interpreted with caution owing to the means
      by which the results were analysed, the length of follow-up, and concerns about
      the ability of FEV1% to accurately represent changes in lung health. Although the
      increase in QALYs is expected to be lower with colistimethate sodium DPI than
      with nebulised tobramycin, a price for this intervention had not been agreed at
      the time of the assessment. Depending on the price of colistimethate sodium DPI,
      this results either in a situation whereby colistimethate sodium DPI is dominated
      by nebulised tobramycin or in one whereby the incremental cost-effectiveness of
      nebulised tobramycin compared with colistimethate sodium DPI is in the range of
      L24,000-277,000 per QALY gained. The economic analysis also suggests that, given
      its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of <
      L30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess
      the longer-term (>= 12 months) efficacy of colistimethate sodium DPI and
      tobramycin DPI in comparison with nebulised treatments would be beneficial. Such
      a study should include the direct assessment of HRQoL using a relevant preference
      based instrument. Future studies should ensure that the European Medicines Agency
      guidelines are adhered to. In addition, high-quality research concerning the
      relationship between forced expiratory volume in first second % (FEV1%) predicted
      or other measures of lung function and survival/health-related quality of life
      (HRQoL) would be useful. STUDY REGISTRATION: PROSPERO CRD42011001350. FUNDING:
      The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 24290165
TI  - Extracellular adenosine 5'-triphosphate and lipopolysaccharide induce interleukin
      1beta release in canine blood.
AB  - Binding of extracellular adenosine 5'-triphosphate (ATP) or lipopolysaccharide
      (LPS) to the damage-associated molecular pattern receptor P2X7 or the pathogen
      associated molecular pattern receptor Toll-like receptor (TLR)4, respectively,
      can induce the release of the pleiotropic cytokine interleukin (IL)-1beta in
      humans and mice. However, the release of IL-1beta in dogs remains poorly defined.
      Using a canine IL-1beta enzyme-linked immunosorbent assay, this study
      investigated whether ATP or LPS could induce IL-1beta release in a canine blood
      based assay. Short-term incubations (30 min) with ATP induced IL-1beta release in
      LPS-primed canine blood, and this process could be near-completely impaired by
      the P2X7 antagonist, A438079. In contrast, ATP failed to induce IL-1beta release
      from blood not primed with LPS. ATP-induced IL-1beta release was observed with
      LPS-primed blood from eight different pedigrees or cross breeds. Long-term
      incubations (24h) with LPS induced IL-1beta release in canine blood in a
      concentration-dependent manner. This process was not altered by co-incubation
      with A438079. LPS-induced IL-1beta release was observed with blood from 10
      different pedigrees or cross breeds. These results demonstrate that both
      extracellular ATP and LPS can induce IL-1beta release in dogs, and that ATP- but
      not LPS-induced IL-1beta release in blood is dependent on P2X7 activation. These
      findings support the role of both P2X7 and TLR4 in IL-1beta release in dogs.

PMID- 24290166
TI  - Right ventricular plasticity in a porcine model of chronic pressure overload.
AB  - BACKGROUND: Ventricular-arterial coupling is a measure of the relationship
      between ventricular contractility and afterload. We sought to determine the
      relationship between ventricular-arterial coupling and right ventricular (RV)
      remodeling in a novel porcine model of progressive pulmonary hypertension (PH).
      METHODS: Chronic PH was induced in pigs by ligation of the left pulmonary artery
      (PA) followed by 5 weekly injections of cyanoacrylate to progressively obstruct
      the right lower lobe arteries (PH group, n = 10). At 6 weeks, 5 PH animals
      underwent reperfusion of the left lung through conduit anastomosis to decrease RV
      afterload, whereas 5 other animals received no treatment. Five sham-operated
      piglets were used as controls. RV function was assessed using echocardiography
      and conductance catheterization. RV gene expression of beta-myosin heavy chain
      (beta-MHC) and B-type natriuretic peptide (BNP) were quantified by polymerase
      chain reaction. RESULTS: At 6 weeks, compared with controls, the PH group had
      higher mean PA pressure (32 +/- 6 vs 14 +/- 2 mm Hg, p < 0.01). The increase in
      RV elastance was insufficient to compensate for the increase in pulmonary
      arterial elastance in the PH group and altered ventricular-arterial coupling
      occurred (0.65 +/- 0.16 vs 1.28 +/- 0.14, p < 0.01). The degree of ventricular
      arterial uncoupling was related to RV enlargement and systolic dysfunction.
      Ventricular-arterial uncoupling and increased RV mass index were associated with
      up-regulation of beta-MHC and BNP expression. CONCLUSIONS: Ventricular-arterial
      coupling is closely associated with ventricular remodeling and systolic function
      as well as contractile and BNP gene expression. Dynamic changes in myosin
      expression may determine RV work efficiency in PH.

PMID- 24290167
TI  - Evolving experience with explantation from Berlin Heart EXCOR ventricular assist
      device support in children.

PMID- 24290169
TI  - The courage to push: donors and recipients.

PMID- 24290168
TI  - A novel link between G6PD deficiency and hemolysis in patients with continuous
      flow left ventricular assist devices.

PMID- 24290171
TI  - Editorial on "segmented flow and curtain flow chromatography: overcoming the wall
      effect and heterogeneous bed structures" by R.A. Shalliker and H. Ritchie.

PMID- 24290170
TI  - Analysis of mixtures of fatty acids and fatty alcohols in fermentation broth.
AB  - Microbial production of fatty acids and fatty alcohols has attracted increasing
      concerns because of energy crisis and environmental impact of fossil fuels.
      Therefore, simple and efficient methods for the extraction and quantification of
      these compounds become necessary. In this study, a high-performance liquid
      chromatography-refractive index detection (HPLC-RID) method was developed for the
      simultaneous quantification of fatty acids and fatty alcohols in these samples.
      The optimum chromatographic conditions are C18 column eluted with
      methanol:water:acetic acid (90:9.9:0.1, v/v/v); column temperature, 26 degrees C;
      flow rate, 1.0mL/min. Calibration curves of all selected analytes showed good
      linearity (r(2)>=0.9989). The intra-day and inter-day relative standard
      deviations (RSDs) of the 10 compounds were less than 4.46% and 5.38%,
      respectively, which indicated that the method had good repeatability and
      precision. Besides, a method for simultaneous extraction of fatty acids and fatty
      alcohols from fermentation broth was optimized by orthogonal design. The optimal
      extraction conditions were as follows: solvent, ethyl acetate; solvent to sample
      ratio, 0.5:1; rotation speed, 2min at 260rpm; extraction temperature, 10 degrees
      C. This study provides simple and fast methods to simultaneously extract and
      quantify fatty acids and fatty alcohols for the first time. It will be useful for
      the study of microbial production of these products. 

PMID- 24290172
TI  - Mixed hemimicelles solid-phase extraction based on ionic liquid-coated Fe3O4/SiO2
      nanoparticles for the determination of flavonoids in bio-matrix samples coupled
      with high performance liquid chromatography.
AB  - A novel magnetic solid-phase extraction (MSPE) method based on mixed hemimicelles
      of room temperature ionic liquids (RTILs) coated Fe3O4/SiO2 nanoparticles (NPs)
      was developed for simultaneous extraction of trace amounts of flavonoids in bio
      matrix samples. A comparative study on the use of RTILs (C16mimBr) and CTAB
      coated Fe3O4/SiO2 NPs as sorbents was presented. Owing to bigger adsorption
      amounts for analytes, RTILs-coated Fe3O4/SiO2 NPs was selected as MSPE materials
      and three analytes luteolin, quercetin and kaempferol can be quantitatively
      extracted and simultaneously determined coupled with high performance liquid
      chromatography (HPLC) in urine samples. No interferences were caused by proteins
      or endogenous compounds. Good linearity (R(2)>0.9993) for all calibration curves
      was obtained, and the limits of detection (LOD) for luteolin, quercetin and
      kaempferol were 0.10 ng/mL, 0.50 ng/mL and 0.20 ng/mL in urine samples,
      respectively. Satisfactory recoveries (93.5-97.6%, 90.1-95.4% and 93.3-96.6% for
      luteolin, quercetin and kaempferol) in biological matrices were achieved. It was
      notable that while using a small amount of Fe3O4/SiO2 NPs (4.0 mg) and C16mimBr
      (1.0 mg), satisfactory preconcentration factors and extraction recoveries for the
      three flavonoids were obtained. To the best of our knowledge, this is the first
      time a mixed hemimicelles MSPE method based on RTILs and Fe3O4/SiO2 NPs magnetic
      separation has ever been used for pretreatment of complex biological samples.

PMID- 24290173
TI  - Ultrasound-assisted extraction and quantitation of oils from Syzygium aromaticum
      flower bud (clove) with supercritical carbon dioxide.
AB  - This study evaluated ultrasound-assisted supercritical carbon dioxide (USC-CO2)
      extraction for determining the extraction yields of oils and the contents of
      eugenol, beta-caryophyllene, eugenyl acetate and alpha-humulene from clove buds.
      Compared to traditional SC-CO2 extraction, USC-CO2 extraction might provide a
      13.5% increase in the extraction yield for the oil while utilizing less severe
      operating parameters, such as temperature, pressure, CO2 flow rate and the time
      consumed by the process. Our results were comparable to those obtained using the
      heat reflux extraction method, though the yield was improved by 20.8% using USC
      CO2. In kinetic studies, the USC-CO2 extraction of clove oil followed second
      order kinetics. The activation energy for the oil extraction was 76.56kJ/mol. The
      USC-CO2 procedure facilitated the use of mild extraction conditions, improved
      extraction efficiency and the quality of products and is a potential method for
      industry. 

PMID- 24290174
TI  - High-throughput and sensitive screening of compounds with deoxyribonucleic acid
      binding activity by a high-performance liquid chromatography-tandem mass
      spectrometry-fluorescence detection technique using palmatine as a fluorescence
      probe.
AB  - A high-throughput biochemical detection method based on the combination of high
      performance liquid chromatography (HPLC), multiple-stage mass spectrometry
      (MS(n)) and DNA-binding activity assay was developed and validated for the
      simultaneous screening and identification of DNA-binding compounds in complex
      samples. Palmatine was used as a sensitive, nontoxic and environmentally friendly
      DNA fluorescence probe. HPLC fingerprints, ultraviolet absorption spectra, MS(n)
      fragments of components, and DNA-binding activity profiles could be
      simultaneously recorded during real-time analysis. Using the proposed method, 25
      compounds were identified from Lophatherum gracile Brongn extracts, of which 18
      were novel compounds first identified in these extracts. Nineteen compounds
      showed DNA-binding activity, most of which were flavone glycosides, with distinct
      dose-effect and structure-activity relationships. The method was validated and
      was proven to have a good linearity in the range of concentrations used in the
      study. The limit of detection was 0.2020nmol. Our study indicated that the
      proposed method was sensitive, accurate, precise and reliable to be used for
      simultaneous screening and identification of DNA-binding compounds in complex
      samples. 

PMID- 24290175
TI  - Influence of gait speed on the control of mediolateral dynamic stability during
      gait initiation.
AB  - This study investigated the influence of gait speed on the control of
      mediolateral dynamic stability during gait initiation. Thirteen healthy young
      adults initiated gait at three self-selected speeds: Slow, Normal and Fast. The
      results indicated that the duration of anticipatory postural adjustments (APA)
      decreased from Slow to Fast, i.e. the time allocated to propel the centre of mass
      (COM) towards the stance-leg side was shortened. Likely as an attempt at
      compensation, the peak of the anticipatory centre of pressure (COP) shift
      increased. However, COP compensation was not fully efficient since the results
      indicated that the mediolateral COM shift towards the stance-leg side at swing
      foot-off decreased with gait speed. Consequently, the COM shift towards the swing
      leg side at swing heel-contact increased from Slow to Fast, indicating that the
      mediolateral COM fall during step execution increased as gait speed rose.
      However, this increased COM fall was compensated by greater step width so that
      the margin of stability (the distance between the base-of-support boundary and
      the mediolateral component of the "extrapolated centre of mass") at heel-contact
      remained unchanged across the speed conditions. Furthermore, a positive
      correlation between the mediolateral extrapolated COM position at heel-contact
      and step width was found, indicating that the greater the mediolateral COM fall,
      the greater the step width. Globally, these results suggest that mediolateral APA
      and step width are modulated with gait speed so as to maintain equivalent
      mediolateral dynamical stability at the time of swing heel-contact. 

PMID- 24290176
TI  - Flow-perfusion interferes with chondrogenic and hypertrophic matrix production by
      mesenchymal stem cells.
AB  - Flow-perfusion is being promoted as a way to grow tissue-engineered cartilage in
      vitro. Yet, there is a concern that flow-perfusion may induce unwanted mechanical
      effects on chondrogenesis and terminal differentiation. Therefore, the aim of
      this study is to evaluate the effect of fluid flow on chondrogenesis and
      chondrocyte hypertrophy of MSCs in a well-established pellet culture model. Human
      MSC pellets were mounted into 3D-printed porous scaffolds in basic chondrogenic
      differentiation medium, containing TGF-beta2. Constructs were then allowed to
      form cartilaginous matrix for 18 days, before they were transferred to a custom
      built flow-perfusion system. A continuous flow of 1.22ml min(-1) was applied to
      the constructs for 10 days. Controls were maintained under static culture
      conditions. To evaluate chondrogenic and hypertrophic differentiation, RNA was
      isolated at day 20 and 28 and histology, immunohistochemistry and western blot
      analyses were performed after 28 days of culture. Abundant matrix was formed in
      the constructs, but production of chondrogenic and hypertrophic matrix components
      was affected by flow-perfusion. Although gene expression levels of the (late)
      hypertrophic and osteogenic marker osteocalcin increased by flow-perfusion, this
      did not result in more collagen type X protein deposition. Decreased GAG release,
      in combination with diminished collagen II staining, indicates reduced
      chondrogenesis in response to flow-perfusion. Caution should thus be taken when
      applying flow-perfusion to cultures to improve nutrient diffusion. Although we
      show that it is possible to influence the differentiation of chondrogenic
      differentiated MSCs by flow-perfusion, effects are inconsistent and strongly
      donor-dependent.

PMID- 24290177
TI  - Finite element analysis of customized reconstruction plates for mandibular
      continuity defect therapy.
AB  - Large mandibular continuity defects pose a significant challenge in oral
      maxillofacial surgery. One solution to this problem is to use computer-guided
      surgical planning and additive manufacturing technology to produce patient
      specific reconstruction plates. However, when designing customized plates, it is
      important to assess potential biomechanical responses that may vary substantially
      depending on the size and geometry of the defect. The aim of this study was to
      assess the design of two customized plates using finite element method (FEM).
      These plates were designed for the reconstruction of the lower left mandibles of
      two ameloblastoma cases (patient 1/plate 1 and patient 2/plate 2) with large bone
      resections differing in both geometry and size. Simulations revealed maximum von
      Mises stresses of 63 MPa and 108 MPa in plates 1 and 2, and 65 MPa and 190 MPa in
      the fixation screws of patients 1 and 2. The equivalent strain induced in the
      bone at the screw-bone interface reached maximum values of 2739 micro-strain for
      patient 1 and 19,575 micro-strain for patient 2. The results demonstrate the
      influence of design on the stresses induced in the plate and screw bodies. Of
      particular note, however, are the differences in the induced strains.
      Unphysiologically high strains in bone adjacent to screws can cause micro-damage
      leading to bone resorption. This can adversely affect the anchoring capabilities
      of the screws. Thus, while custom plates offer optimal anatomical fit, attention
      should be paid to the expected physiological forces on the plates and the induced
      stresses and strains in the plate-screw-bone assembly.

PMID- 24290178
TI  - Two-leg alternate loading model--a different approach to biomechanical
      investigations of fixation methods of the injured pelvic ring with focus on the
      pubic symphysis.
AB  - The dorsal component of the pelvic ring is considered to be the most essential
      element for the stability of the pelvic ring. None of the current biomechanical
      set-ups include the effect of shear stresses by alternating loads that the pelvic
      ring has to withstand during walking. We hypothesize that a biomechanical test
      set-up with two-leg alternate loading will lead to stress imitation at the pubic
      symphysis that are more similar to existing strains than other test set-ups, and
      would, therefore, be more adequate for biomechanical testing of fixation methods.
      A new biomechanical two-leg standing test set-up with an alternate pelvic loading
      was constructed and was validated with six human pelvises from fresh frozen
      cadavers. Three-dimensional motion tracking was performed. The specimens were
      subjected to a non-destructive quasi-static test and a non-destructive cyclic
      test with progressive load amplitude from 170 N to 340 N over 1000 cycles. The
      initial rotational 'range of motion' and 'mean displacement' around the vertical
      axis for a pre-load of 170 N was about 0.3 degrees  and 0.2 degrees ,
      respectively, increasing by 0.1-0.2 degrees  at a load of 340 N. The rotation
      around the vertical axis and the translation along the frontal horizontal axis
      confirmed the stability of the pubic symphysis. The rate of ascend of
      displacements decreased, once the rotation reached 1 degrees  or the translation
      reached 1mm. The current biomechanical test set-up was compared with previous
      clinical findings, and the method was found valid for measuring inter-segmentary
      movements at the pubic symphysis.

PMID- 24290179
TI  - [Compliance with antiretroviral therapy in HIV-infected adolescents in
      Brazzaville, Congo].

PMID- 24290180
TI  - [Acute osteomyelitis of the clavicle in the newborn infant: a case report].
AB  - Acute osteomyelitis of the clavicle accounts for less than 3% of osteomyelitis
      cases, with its usual location in the middle third. It may be hematogenous, due
      to contiguity, or secondary to catheterization of the subclavian vein or neck
      surgery. The diagnosis is often delayed, and clinical symptoms may simulate
      obstetric brachial plexus palsy in young children. We report a new case of
      osteomyelitis of the clavicle in a 30-day-old newborn. 

PMID- 24290181
TI  - [Autonomic regulation and bradycardia during the neonatal period].
AB  - The high frequency of bradycardia observed during the neonatal period requires
      cardiac monitoring but also understanding its intrinsic mechanisms, including
      responsiveness of the autonomic nervous system (ANS). Heart rate variability and
      spontaneous baroreflex analysis can help understand the autonomic dysregulation
      of cardiorespiratory control, possibly responsible for sudden infant death. In
      clinical neonatology practice, neonatal bradycardia does not warrant continuation
      of monitoring if it remains isolated, asymptomatic, and short (<10 s), followed
      by a rapid cardiac acceleration indicating an adapted sympathetic response.
      Further evaluation of ANS responsiveness is possible for newborns including
      analyzing the complexity of the heart rate and respiratory variability. This
      allows better targeting children with high risk after discharge. The real-time
      evaluation of autonomic regulation could become a valuable tool in clinical
      practice. 

PMID- 24290182
TI  - [Neonatal cervical artery dissection secondary to birth trauma].
AB  - Cervical artery dissection is rare in the neonatal period and is most often
      caused by birth injury during dystocic labor. The severity of this pathology is
      due to the possibility of serious neurological complications. We report a case of
      a male newborn who was born vaginally after shoulder dystocia. The extraction was
      difficult, resulting in a fracture of the right humerus. On the second day of
      life, the child presented generalized clonic convulsions. Computed tomography of
      the brain showed an ischemic stroke in the territory of the right middle cerebral
      artery, the territory of the right posterior cerebral artery, and the right
      lenticulostriate and capsular regions. Doppler ultrasonography and magnetic
      resonance angiography showed bilateral carotid artery thrombosis and dissection
      at the left common carotid artery and its two branches and the right vertebral
      artery. We discuss the mechanisms of this pathology and we emphasize preventive
      measures. 

PMID- 24290183
TI  - [Adolescents consulting at the pediatric emergency room for psychological or
      psychiatric reasons].
AB  - INTRODUCTION: The number of pediatric emergency consultations for psychological
      or psychiatric reasons continues to rise, raising the question of the adequacy of
      existing facilities. Our aim was therefore to identify and characterize a
      population of adolescents consulting at the pediatric emergency unit at Rouen
      university hospital. METHODS: This study was conducted from 1 January to 31
      December 2006. We distinguished three types of variables in adolescents
      consulting at the pediatric emergency unit. The main objective was to describe
      the profile and requirements of these young patients and their subsequent care
      management as compared to that of other studies. RESULTS: Of the 400 patients
      consulting over 12years of age, 69% were female and the average age was
      13.8years. These cases were mainly attempted suicide in girls and conduct
      disorder in boys; hospitalization was at the request of the family. These
      consultations were directly linked to the school calendar and 70% required
      hospitalization. DISCUSSION: We both analyzed and compared the results of this
      study to those of other studies to propose solutions to improve the care of these
      young patients.

PMID- 24290185
TI  - [Neonatal suppurative parotidis: a case report and review of the literature].
AB  - Suppurative parotidis is an uncommon disease in newborns, with limited
      information available on its pathogenesis and management: approximately 50 cases
      have been reported in the literature. Diagnosis is based on clinical signs. The
      predominant organism is Staphylococcus aureus. The administration of empiric
      antimicrobial therapy is an essential part of the management in very young
      patients. Prognosis is good and recurrence of the disease is unusual. We describe
      a 21-day-old newborn who presented with fever and unilateral swelling of the
      parotid region, and provide a literature review.

PMID- 24290186
TI  - [Liability of the pediatrician and court reporting of child abuse].

PMID- 24290187
TI  - [Feeding practices in 6-to-24-month-old children in Yaounde, Cameroon:
      relationship with their nutritional status].
AB  - INTRODUCTION: Shifting from breastfeeding to solid food is known as the
      complementary feeding period. When complementary feeding is inadequate,
      malnutrition results in most cases. These practices differ depending on cultural
      and religious backgrounds as well as geographical location. Ruel and Menon
      studied the relationship between feeding practices during diversification and
      nutritional status of children at 6 and 36 months, using a score called the
      Infant and Child Feeding Index (ICFI). This ICFI scored feeding practices such as
      breastfeeding, bottle-feeding, food diversity, and meal frequency, which has
      never been studied in Cameroon. OBJECTIVE: The aim of this study was to describe
      actual feeding practices in children in our context as well as to investigate
      their relationship with children's nutritional status. PATIENTS AND METHODS: We
      carried out a cross-sectional study throughout the month of January 2011 at the
      Chantal-Biya Foundation. Mothers completed a questionnaire on how their infants
      were fed at birth, the initiation of complementary food, and feeding practices
      for the 3 days before the survey. The children's anthropometric parameters were
      noted. All mothers coming for vaccination or vitamin A supplementation for their
      children aged between 6 and 24 months were enrolled in the study. RESULTS: We
      enrolled 197 mothers and their infants. Breastfeeding was the main feeding method
      at birth, but was exclusive until 6 months for only 15 % of the infants. Three
      quarter of nursing mothers started adding complementary food at age 4-6 months,
      using pap. Half of the children did not receive animal products, fruits, or
      vegetables. When applying the ICFI to these practices, it appeared that the
      various diversification practices scored less than 8 for 50% of the population. A
      positive association was noted between the ICFI and nutritional status, as
      expressed by height-of-age Z-score (HAZ) and the weight-for-age Z-score (WAZ).
      CONCLUSION: We concluded that the codified feeding practices with respect to Ruel
      and Menon's ICFI are associated with the nutritional status of children between 6
      and 24 months in Yaounde, Cameroon.

PMID- 24290188
TI  - [Septic cavernous sinus thrombosis following ethmoiditis: a case report].
AB  - Acute ethmoiditis is a rare infection of ethmoidal cells. The pathognomonic sign
      is an edema of the internal corner of the eye. Imaging may be necessary to verify
      the absence of orbital or endocranial complications. Thrombophlebitis of the
      cavernous sinus is a serious complication of this infectious process. We report
      the case of an 11-year-old boy who presented with ethmoiditis complicated with
      thrombophlebitis of the cavernous sinus, with right hemiplegia and left Bell
      palsy sequelae. Early diagnosis of this disorder and urgent therapy are
      essential. Treatment is based on the antibiotic therapy. 

PMID- 24290189
TI  - [Asthma: an epithelial disease?].

PMID- 24290190
TI  - [Renal candidal bezoar: case report and review of the literature].
AB  - Candida infection is a relatively common hematogenous nosocomial infection in
      immunocompromised patients. However, renal disease remains unusual. The mode of
      presentation in the case reported herein was lumbar pain with fever and
      hydronephrosis of the left kidney due to a fungal bezoar in the renal pelvis.
      Clinical and biological suspicion of this disease must quickly lead to ultrasound
      examination to confirm the diagnosis. 

PMID- 24290191
TI  - Disintegration rate, gamma-ray emission probabilities and metastable half-life
      measurements of 67Ga.
AB  - The procedure for determining the (67)Ga disintegration rate by a primary method
      is described. The proposed triple 4pibeta-gamma coincidence system consists of a
      thin window gas-flow 4pi proportional counter (PC) coupled to a NaI(Tl)
      scintillator and a HPGe crystal. Independent pulse height and occurrence time
      information is provided for the three detector outputs by means of a Software
      Coincidence System. Separate spectrometry measurements with a n-type reversed
      electrode coaxial Ge detector (REGe) were performed for obtaining gamma-ray
      emission probabilities per decay. Accurate values of disintegration rate, gamma
      ray emission probabilities and the metastable half-life were achieved. 

PMID- 24290193
TI  - The domestication and evolutionary ecology of apples.
AB  - The cultivated apple is a major fruit crop in temperate zones. Its wild
      relatives, distributed across temperate Eurasia and growing in diverse habitats,
      represent potentially useful sources of diversity for apple breeding. We review
      here the most recent findings on the genetics and ecology of apple domestication
      and its impact on wild apples. Genetic analyses have revealed a Central Asian
      origin for cultivated apple, together with an unexpectedly large secondary
      contribution from the European crabapple. Wild apple species display strong
      population structures and high levels of introgression from domesticated apple,
      and this may threaten their genetic integrity. Recent research has revealed a
      major role of hybridization in the domestication of the cultivated apple and has
      highlighted the value of apple as an ideal model for unraveling adaptive
      diversification processes in perennial fruit crops. We discuss the implications
      of this knowledge for apple breeding and for the conservation of wild apples. 

PMID- 24290192
TI  - Ldb1 complexes: the new master regulators of erythroid gene transcription.
AB  - Elucidation of the genetic pathways that control red blood cell development has
      been a central goal of erythropoiesis research over the past decade. Notably,
      data from several recent studies have provided new insights into the regulation
      of erythroid gene transcription. Transcription profiling demonstrates that
      erythropoiesis is mainly controlled by a small group of lineage-restricted
      transcription factors [Gata binding protein 1 (Gata1), T cell acute lymphocytic
      leukemia 1 protein (Tal1), and Erythroid Kruppel-like factor (EKLF; henceforth
      referred to as Klf1)]. Binding-site mapping using ChIP-Seq indicates that most
      DNA-bound Gata1 and Tal1 proteins are contained within higher order complexes
      (Ldb1 complexes) that include the nuclear adapters Ldb1 and Lmo2. Ldb1 complexes
      regulate Klf1, and Ldb1 complex-binding sites frequently colocalize with Klf1 at
      erythroid genes and cis-regulatory elements, indicating strong functional synergy
      between Gata1, Tal1, and Klf1. Together with new data demonstrating that Ldb1 can
      mediate long-range promoter-enhancer interactions, these findings provide a
      foundation for the first comprehensive models of the global regulation of
      erythroid gene transcription. 

PMID- 24290195
TI  - Women's perceptions of social support during labour: development, reliability and
      validity of the Birth Companion Support Questionnaire.
AB  - OBJECTIVE: to develop and test the reliability and validity of a research
      instrument to measure women's perceptions of social support provided during
      labour by at least one lay birth companion. DESIGN: a cross-sectional study was
      carried out from April 2009 to February 2010. SETTING: non-tertiary hospital in
      the outer western region of Brisbane, Australia. PARTICIPANTS: six registered
      midwives and 10 postnatal women reviewed the instrument. The instrument was then
      completed by 293 inpatient women who had experienced a vaginal birth.
      MEASUREMENTS AND FINDINGS: the Birth Companion Support Questionnaire (BCSQ) was
      developed and its reliability and validity were evaluated in this study. An
      exploratory factor analysis was performed on the final instrument using principal
      component analysis with an oblique (Promax) rotation. This process suggested two
      subscales: emotional support and tangible support. The questionnaire was found to
      be reliable and valid for use in midwifery research. KEY CONCLUSIONS: the BCSQ is
      an appropriate instrument to measure women's perceptions of lay birth companion
      support during labour. IMPLICATIONS FOR PRACTICE: this is the first rigorous
      study to develop and test a measure of social support in labour which is critical
      at a time when policy makers and health planners need to consider the needs of
      birthing women and their network of support friends and family.

PMID- 24290194
TI  - Diarylheptanoids from the bark of black alder inhibit the growth of sensitive and
      multi-drug resistant non-small cell lung carcinoma cells.
AB  - An extended study of minor diarylheptanoids from the bark of black alder has
      resulted in the isolation of twenty diarylheptanoids, ten of which have not
      previously been reported (14-18, 20-24). The structures and configurations of all
      compounds were elucidated by NMR, HRESIMS, UV, IR, and CD. The anti-cancer
      potency of twenty diarylheptanoids and four previously isolated compounds (7, 10,
      12, 13) was investigated in human non-small cell lung carcinoma cell lines
      (sensitive and multi-drug resistant variants) as well as in normal human
      keratinocytes. Diarylheptanoids with a p-coumaroyl group, 14 and 18,
      platyphylloside (1), platyphyllonol-5-O-beta-D-xylopyranoside (2), alnuside B (4)
      and hirsutenone (9) exhibited strong anti-cancer activity, considerably higher
      than diarylheptanoid curcumin, which served as a positive control. Compounds 4,
      9, 14, and 18 displayed significant selectivity towards the cancer cells.
      Structure/activity analysis of twenty-four closely related diarylheptanoids
      revealed a high dependence of cytotoxic action on the presence of a carbonyl
      group at C-3. Substitution of a heptane chain on C-5 and a number of hydroxyl
      groups in the aromatic rings also emerged as a significant structural feature
      that influenced their cytotoxic potential.

PMID- 24290196
TI  - The experiences of women who quit smoking during pregnancy and how they dealt
      with their spouses' continued smoking.
AB  - OBJECTIVE: to explore how pregnant women in Taiwan dealt with their spouses who
      continued to smoke and with passive smoking during their own process of quitting
      and abstaining. DESIGN: a qualitative study using an oral history approach. Data
      were collected via tape-recorded open-ended interviews. All interviews were
      transcribed verbatim. Data were analysed using narrative analysis. SETTING: the
      homes of the participant women living in the district of a regional hospital of
      eastern Taiwan. PARTICIPANTS: a purposive sample of 10 Taiwanese women who had
      quit smoking while pregnant was recruited at 1-3 months following the birth of
      their infants. FINDINGS: five major themes emerged: (1) the women coping with
      tobacco addiction on their own, (2) creating a non-smoking section or environment
      at home, (3) dealing with passive smoking, (4) conflict over the wife's
      sensitivity to her spouse's residual tobacco smell, and (5) allowing the husband
      to continue smoking to avoid conflicts. KEY CONCLUSIONS: the pregnant women were
      expected by their spouses to quit smoking, yet the husbands continued to smoke.
      Women had to struggle to quit smoking on their own. The findings from this study
      support the need to listen to pregnant women's stories, as this is paramount to
      understanding their experiences of tobacco-use reduction and cessation, and for
      developing gender appropriate interventions to support their efforts.
      IMPLICATIONS FOR PRACTICE: health care providers should encourage and help
      pregnant women who are willing to quit smoking. This help could be more family
      centred instead of focusing on the pregnant women alone, and therefore involve
      educating the spouse to support his wife.

PMID- 24290197
TI  - Being alone in silence - mothers' experiences upon confirmation of their baby's
      death in utero.
AB  - OBJECTIVE: to explore mothers' experiences of the confirmation of ultrasound
      examination results and how they were told that their baby had died in-utero.
      DESIGN: in-depth interviews. SETTING: Sweden. PARTICIPANTS: 26 mothers of
      stillborn babies. MEASUREMENT: narratives were analysed using a qualitative
      content analysis with an inductive approach. FINDINGS: the mothers experienced
      that silence prevailed during the entire process of confirming the ultrasound
      results. Typically all present in the ultrasound room were concentrating and
      focusing on what they observed on the screen, no one spoke to the mother. The
      mothers had an instinctive feeling that their baby might be dead based on what
      they observed on the ultrasound screen and on their interpretation of the body
      language of the clinicians and midwives. Some mothers reported a time delay in
      receiving information about their baby's death. Experiencing uncertainty about
      the information received was also noticed. CONCLUSION: mothers emphasised an
      awareness of silence and feelings of being completely alone while being told of
      the baby's death. IMPLICATION FOR PRACTICE: the prevalence of silence during an
      ultrasound examination may in certain cases cause further psychological trauma
      for the mother of a stillborn baby. One way to move forward given these results
      may be to provide obstetric personnel sufficient training on how difficult
      information might be more effectively and sensitively provided in the face of an
      adverse pregnancy outcome.

PMID- 24290198
TI  - Applicability of the prehospital termination of resuscitation rule in an area
      dense with hospitals in Tokyo: a single-center, retrospective, observational
      study: is the pre hospital TOR rule applicable in Tokyo?
AB  - BACKGROUND: It is unclear whether the prehospital termination of resuscitation
      (TOR) rule is applicable in specific situations such as in areas extremely dense
      with hospitals. OBJECTIVES: The objective of the study is to assess whether the
      prehospital TOR rule is applicable in the emergency medical services system in
      Japan, specifically, in an area dense with hospitals in Tokyo. METHODS: This
      study was a retrospective, observational analysis of a cohort of adult out-of
      hospital cardiopulmonary arrest (OHCA) patients who were transported to the
      University of Tokyo Hospital from April 1, 2009, to March 31, 2011. RESULTS:
      During the study period, 189 adult OHCA patients were enrolled. Of the 189
      patients, 108 patients met the prehospital TOR rule. The outcomes were
      significantly worse in the prehospital TOR rule-positive group than in the
      prehospital TOR-negative group, with 0.9% vs 11.1% of patients, respectively,
      surviving until discharge (relative risk [RR], 1.11; 95% confidence interval
      [CI], 1.03-1.21; P = .0020) and 0.0% vs 7.4% of patients, respectively,
      discharged with a favorable neurologic outcome (RR, 1.08; 95% CI, 1.02-1.15; P =
      .0040). The prehospital TOR rule had a positive predictive value (PPV) of 99.1%
      (95% CI, 96.3-99.8) and a specificity of 90.0% (95% CI, 60.5-98.2) for death and
      a PPV of 100.0% (95% CI, 97.9-100.0) and a specificity of 100.0% (95% CI, 61.7
      100.0) for an unfavorable neurologic outcome. CONCLUSIONS: This study suggested
      that the prehospital TOR rule predicted unfavorable outcomes even in an area
      dense with hospitals in Tokyo and might be helpful for identifying the OHCA
      patients for whom resuscitation efforts would be fruitless.

PMID- 24290199
TI  - MR cholangiopancreatography of the pancreas and biliary system: a review of the
      current applications.
AB  - MR cholangiopancreatography (MRCP) is still a rapidly evolving technique, but it
      has been already accepted as clinically useful and is widely used to evaluate
      biliary or pancreatic diseases. The advantages of this technique are that it does
      not use contrast media or ionizing radiation, it is noninvasive and complication
      free, and the examination is relatively short. MRCP has high sensitivity and
      specificity for diagnosing biliary dilatation and for determining the site and
      cause of stenosis. With further improvements of hardware and technique, MRCP is
      expected to replace diagnostic endoscopic retrograde cholangiopancreatography to
      examine the biliary and pancreatic ducts in the near future. The other
      applications include evaluation of primary sclerosing cholangitis, stenosis after
      liver transplantation, and bilioenteric anastomoses. This article reviews the
      current applications of MRCP in the evaluation of the pancreas and the biliary
      system. 

PMID- 24290200
TI  - Imaging biliary strictures--a pictorial review.
AB  - The diagnosis of biliary diseases may be delayed or missed because of an
      unpredictable clinical course and presentation. Some biliary diseases carry the
      risk of morbidity and mortality and are difficult to treat. The purpose of this
      article is to revisit the various causes and the appearances of biliary
      strictures on different imaging modalities and to emphasize the role of magnetic
      resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP)
      in their evaluation compared with endoscopic retrograde cholangiopancreatography.
      MRI with MRCP is advantageous to endoscopic retrograde cholangiopancreatography
      for being a 1-stop shop to provide biliary, soft tissue, and vascular information
      that is helpful for planning intervention or surgery. Thus it serves as a superb
      imaging modality for the evaluation of biliary strictures. 

PMID- 24290201
TI  - Endovascular embolization: review of currently available embolization agents.
AB  - Percutaneous vascular embolization is one of the major applications of
      interventional radiology. A wide variety of embolization agents are currently
      available for clinical use. The interventional radiologist needs to be up to date
      with the newer and different types of embolic agents available along with their
      biopharmaceutical characteristics, strengths, and weaknesses that have been
      reviewed. For the purpose of this review, we have classified embolization agents
      into mechanical occlusion devices, particulate agents, and liquid agents, with
      some degree of overlap between some of the agents. 

PMID- 24290202
TI  - Saddle nose: classification and therapeutic management.
AB  - INTRODUCTION: The understanding and treatment of saddle nose have always been a
      surgical challenge. The authors propose a three-stage classification of this
      deformity as well as a treatment strategy adapted to each case. MATERIALS AND
      METHODS: A retrospective study was carried out on 25 patients with saddle nose.
      After defining the three stages of saddle nose: minimal, moderate and major, the
      authors describe the treatment protocol adopted for each stage. RESULTS: This
      series comprised 3 cases of minimal saddle nose, 17 cases of moderate saddle nose
      and 5 cases of major saddle nose. Minimal saddle nose was treated by
      extracorporeal rhinoplasty, an inverted U-shaped conchal graft was used to treat
      moderate saddle nose, and costal cartilage was used to reconstruct major saddle
      nose. Surgical approaches varied according to the technique adopted. Surgical
      revision was never required. CONCLUSION: Saddle nose is a classical condition in
      facial reconstructive surgery. The proposed treatment strategy is based on
      detailed analysis of the clinical signs, resulting in a graduated solution
      adapted to each clinical case according to the severity of the deformity.

PMID- 24290203
TI  - Reducing dietary protein in dairy cow diets: implications for nitrogen
      utilization, milk production, welfare and fertility.
AB  - In light of increasing global protein prices and with the need to reduce
      environmental impact of contemporary systems of milk production, the current
      review seeks to assess the feasibility of reducing levels of dietary CP in dairy
      cow diets. At CP levels between 140 and 220 g/kg DM there is a strong positive
      relationship between CP concentration and dry matter intake (DMI). However, such
      effects are modest and reductions in DMI when dietary CP is below 180 g/kg DM can
      be at least partially offset by improving the digestibility and amino acid
      profile of the undegradable protein (UDP) component of the diet or by increasing
      rumen fermentable energy. Level and balance of intestinally absorbable amino
      acids, in particular methionine and lysine, may become limiting at lower CP
      concentrations. In general the amino acid composition of microbial protein is
      superior to that of UDP, so that dietary strategies that aim to promote microbial
      protein synthesis in the rumen may go some way to correcting for amino acid
      imbalances in low CP diets. For example, reducing the level of NDF, while
      increasing the proportion of starch, can lead to improvements in nitrogen (N)
      utilisation as great as that achieved by reducing dietary CP to below 150 g/kg. A
      systematic review and meta-analysis of responses to rumen protected forms of
      methionine and lysine was conducted for early/mid lactation cows fed diets
      containing ?150 g CP/kg DM. This analysis revealed a small but significant
      (P=0.002) increase in milk protein yield when cows were supplemented with these
      rumen protected amino acids. Variation in milk and milk protein yield responses
      between studies was not random but due to differences in diet composition between
      studies. Cows fed low CP diets can respond to supplemental methionine and lysine
      so long as DMI is not limiting, metabolisable protein (MP) is not grossly
      deficient and other amino acids such as histidine and leucine do not become rate
      limiting. Whereas excess dietary protein can impair reproduction and can
      contribute to lameness, there is no evidence to indicate that reducing dietary CP
      levels to around 140 to 150 g CP/kg DM will have any detrimental effect on either
      cow fertility or health. Contemporary models that estimate MP requirements of
      dairy cows may require refinement and further validation in order to predict
      responses with low CP diets. 

PMID- 24290204
TI  - Synaptic encoding of fear extinction in mPFC-amygdala circuits.
AB  - Retrieval of fear extinction memory is associated with increased firing of
      neurons in the medial prefrontal cortex (mPFC). It is unknown, however, how
      extinction learning-induced changes in mPFC activity are relayed to target
      structures in the amygdala, resulting in diminished fear responses. Here, we show
      that fear extinction decreases the efficacy of excitatory synaptic transmission
      in projections from the mPFC to the basolateral nucleus of the amygdala (BLA),
      whereas inhibitory responses are not altered. In contrast, synaptic strength at
      direct mPFC inputs to intercalated neurons remains unchanged after extinction.
      Moreover, priming stimulation of mPFC projections induced heterosynaptic
      inhibition in auditory cortical inputs to the BLA. These synaptic mechanisms
      could contribute to the encoding of extinction memory by diminishing the ability
      of projections from the mPFC to drive BLA activity while retaining the ability of
      intercalated neurons to inhibit the output nuclei of the amygdala. 

PMID- 24290206
TI  - Effects of integrating hip movements into bridge exercises on electromyographic
      activities of selected trunk muscles in healthy individuals.
AB  - This study aimed to identify the electromyographic (EMG) effects in selected
      trunk muscles after incorporating hip movement into bridging exercise. Twenty-six
      healthy adults (13 men and 13 women) volunteered for this experiment. EMG data (%
      maximum voluntary isometric contraction) were recorded from the rectus abdominis
      (RA), obliquus internus (OI), erector spinae (ES), and multifidus (MF) muscles of
      the dominant side while the subjects performed 3 types of bridging exercise,
      including bridging alone (Bridging 1), bridging with unilateral hip movements
      (Bridging 2), and bridging with bilateral hip movements (Bridging 3) in a sling
      suspension system. The RA and OI showed greater EMG activity during Bridging 2
      and 3 compared to Bridging 1, with the greatest OI activity during Bridging 3 (p
      < 0.05), and the activity of the MF appeared to be greater during Bridging 3 than
      during Bridging 1 and 2 (p < 0.05). Furthermore, the OI/RA and MF/ES ratios were
      significantly higher for Bridging 2 (OI/RA = 1.89 +/- 1.41; MF/ES = 1.03 +/-
      0.19) and Bridging 3 (OI/RA = 2.34 +/- 1.86; MF/ES = 1.03 +/- 0.15) than Bridging
      1 (IO/RA = 1.35 +/- 0.92; MF/ES = 0.98 +/- 0.16). The OI/RA ratio was
      significantly higher for Bridging 3 than for Bridging 2. Based on these results,
      adding hip abduction and adduction, particularly bilateral movements, could be a
      useful method to enhance OI and MF EMG activity and their activities relative to
      global muscles during bridging exercise.

PMID- 24290205
TI  - Supervised calibration relies on the multisensory percept.
AB  - Multisensory plasticity enables us to dynamically adapt sensory cues to one
      another and to the environment. Without external feedback, "unsupervised"
      multisensory calibration reduces cue conflict in a manner largely independent of
      cue reliability. But environmental feedback regarding cue accuracy ("supervised")
      also affects calibration. Here we measured the combined influence of cue accuracy
      and cue reliability on supervised multisensory calibration, using discrepant
      visual and vestibular motion stimuli. When the less reliable cue was inaccurate,
      it alone got calibrated. However, when the more reliable cue was inaccurate, cues
      were yoked and calibrated together in the same direction. Strikingly, the less
      reliable cue shifted away from external feedback, becoming less accurate. A
      computational model in which supervised and unsupervised calibration work in
      parallel, where the former only relies on the multisensory percept, but the
      latter can calibrate cues individually, accounts for the observed behavior. In
      combination, they could ultimately achieve the optimal solution of both external
      accuracy and internal consistency. 

PMID- 24290207
TI  - Tobacco harm reduction: the need for new products that can compete with
      cigarettes.
AB  - Over the last 50 years, the concept of tobacco harm reduction has been well
      established. It is now understood that nicotine itself is not very harmful and
      nicotine replacement therapy products have been widely used as an aid to quit,
      reduce to quit or temporarily abstain from smoking for many years. The popularity
      of the unlicensed electronic cigarette has increased despite an unknown risk
      profile and sinus use in Sweden provides strong evidence in support of a harm
      reduction strategy. The regulatory environment around harm reduction has changed
      in the UK and is continuing to evolve across the globe. The need for more
      appealing, licensed nicotine products capable of competing with cigarettes
      sensorially, pharmacologically and behaviourally is considered by many to be the
      way forward. The significant positive impact on public health that could be
      gained from encouraging people to switch from cigarettes to licensed medicinal
      nicotine products cannot be ignored.

PMID- 24290208
TI  - Relationship between dispositional mindfulness and substance use: findings from a
      clinical sample.
AB  - There has been rapidly increasing interest over the past decade in the potential
      of mindfulness-based approaches to psychological and medical treatment, including
      a recent growth in the area of substance abuse. Thus, the relationship between
      trait mindfulness and substance use has been explored in several studies.
      Results, however, have been mixed. While several studies of college student
      populations have evinced positive correlations between levels of trait
      mindfulness and substance use, the opposite seems to be true in clinical samples,
      with multiple studies showing a negative association. The current study reviews
      research in both non-treatment seeking college students and in clinical samples,
      and examines the relationship between trait mindfulness and substance dependence
      in a clinical sample (N=281). Further, the study assesses the moderating effect
      of avoidant coping that might explain the disparate findings in the clinical
      versus nonclinical samples. 

PMID- 24290209
TI  - The effects of acute exercise on tobacco cravings and withdrawal symptoms in
      temporary abstinent pregnant smokers.
AB  - INTRODUCTION: Smoking during pregnancy is common, and quitting at any point
      during pregnancy can yield benefits to both the fetus and mother. Smoking
      cessation is typically followed by withdrawal symptoms and a strong desire to
      smoke, both of which are likely to contribute to relapse. Research has shown that
      a bout of exercise minimizes cravings and tobacco withdrawal symptoms (TWS) after
      temporary abstinence in smokers, but these findings have not been replicated in
      pregnant smokers. This study examined the effect of 20min of exercise on cravings
      (primary outcome) and TWS (secondary outcomes) among temporary abstinent,
      inactive pregnant smokers. METHODS: Thirty female smokers (Mean(M) age=25.7years,
      Standard Deviation(SD)=5.5; M weeks pregnant=18.2, SD=5.3; Fagerstrom Test for
      Cigarette Dependence=3.3, SD=2.2; M 9.3 cigarettes/day, SD=4.7; M hours
      abstained=17.2, SD=2.8) were randomized to 20 min of mild-to-moderate intensity
      exercise (EC; n=14) or passive (PC; n=16) condition. Cravings and TWS were
      assessed immediately before, during (at 10 min), immediately post, and at 10, 20,
      and 30 min post-condition. RESULTS: A 2 (condition)*6 (time) repeated measures
      ANOVA revealed that the EC significantly (p<0.05) reduced cravings (eta(2)=0.46)
      compared with the PC, across time. Non-significant, but nevertheless, large
      effects were evident favouring the EC over time for TWS restlessness
      (eta(2)=0.34), stress (eta(2)=0.24), irritability (eta(2)=0.21), tension
      (eta(2)=0.15), and depression (eta(2)=0.14). CONCLUSIONS: Consistent with
      previous research, this study reveals that in pregnant smokers, a bout of
      exercise is associated with a reduction in cravings and similar patterns exist
      for TWS. Therefore, exercise may have the potential to assist in the initial
      stages of smoking cessation attempts during pregnancy.

PMID- 24290210
TI  - Integrated cognitive behavioral therapy for cannabis use and anxiety disorders:
      rationale and development.

PMID- 24290211
TI  - Retrospect of hematological malignancies 2012.

PMID- 24290212
TI  - Second-generation tyrosine kinase inhibitors can induce complete molecular
      response in Ph-positive acute lymphoblastic leukemia after allogeneic stem cell
      transplant.

PMID- 24290213
TI  - Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes.
AB  - Allogeneic stem cell transplantation (SCT) is the only treatment with curative
      potential for myelodysplastic syndrome (MDS). The availability of SCT has been
      expanded with the introduction of reduced intensity conditioning for older
      patients and the use of alternative donors. Treatment-related mortality and
      relapse have remained major barriers to uniform success and there is a
      significant need for innovative approaches to improve these outcomes. Encouraging
      results have been reported for patients who lack a human leukocyte antigen
      identical donor with the use of cord blood and haploidentical donors. Improved
      approaches for patient selection and optimization of the timing of SCT are
      needed. New prognostic classification schemas identify risk groups for disease
      outcomes and facilitate decisions with regard to SCT. Patients with intermediate
      2 and high-risk disease and those with therapy-related MDS have a poor prognosis
      with alternative therapies; improved results have been reported with
      hematopoietic transplantation. The optimum timing for SCT is controversial in the
      era of hypomethylating agents. Initial conservative management is indicated for
      patients with low-risk disease. Hematopoietic transplantation remains the only
      curative treatment for patients with MDS and should be used before patients
      overtly progress to advanced disease. Failure to respond to hypomethylating
      agents does not adversely affect the outcome of SCT; these patients might achieve
      durable remissions with hematopoietic transplantation. Refined prognostic markers
      are needed to identify poor prognosis patients to guide patient selection for
      SCT, and novel transplantation approaches are required to reduce the risk of
      disease relapse and complications of the procedure. 

PMID- 24290214
TI  - Prognostic factors and risk models in myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) encompass a hematologically diverse group of
      neoplastic disorders with a common pathological and clinical phenotype but
      distinct underlying biology and variable outcome. The prognosis of MDS depends on
      disease risk features, host factors, and their interaction. Risk stratification
      allows forecasting of disease prognosis and tailoring patient treatment based on
      that risk. The International Prognostic Scoring System (IPSS) served as the first
      widely adopted model for several years. New risk models, including the M.D.
      Anderson risk model and revised IPSS, refine the prognostic power of the IPSS and
      address some of its shortcomings. We are learning more about the biology of the
      disease by uncovering the various genetic and molecular mutations. Those in turn,
      serve as prognostic factors and will be incorporated in the new risk models. 

PMID- 24290215
TI  - Successful long-term treatment of Philadelphia chromosome-negative
      myeloproliferative neoplasms with combination of hydroxyurea and anagrelide.
AB  - BACKGROUND: Resistance or intolerance to either of the 2 favored therapeutic
      choices for MPN is a common clinical challenge. To overcome this, we report our
      successful long-term experience with the combination of low-dose HU and AG.
      PATIENTS AND METHODS: Retrospective review identified 12 patients with essential
      thrombocythemia or polycythemia vera using combination therapy. RESULTS: The mean
      duration of treatment 4.25 years. Combination therapy achieved a 45% median
      platelet count reduction with relatively low daily dose requirements (711 mg HU,
      1.38 mg AG). All but 1 patient achieved partial (25%) or complete response (67%)
      according to European LeukemiaNet criteria. No arterial or venous thrombosis, or
      bleeding events occurred. CONCLUSION: This is the longest follow-up experience of
      an HU and AG combination regimen in MPN. The low-dose combination regimen
      effectively achieved clinical and laboratory response while simultaneously
      minimizing dose-related adverse reactions, and should be the preferred
      therapeutic alternative to third-line agents in MPN patients who are resistant or
      intolerant to monotherapy.

PMID- 24290216
TI  - Are all interferons the same for therapy in polycythemia vera?

PMID- 24290217
TI  - Rationale for targeting the PI3K/Akt/mTOR pathway in myeloproliferative
      neoplasms.
AB  - The chronic myeloproliferative neoplasms (MPNs), are characterized by a Janus
      Kinase (JAK)-2 V617F point mutation but this molecular abnormality does not
      explain by itself the pathogenesis of these disorders, or the phenotypic
      diversity associated with essential thrombocythemia, polycythemia vera (PV), and
      myelofibrosis. Beyond the JAK/signal transducer and activator of transcription
      network, a wide number of molecular alterations were described in MPN including
      the fosfatidilinositolo-3-chinasi (PI3K)/protein kinase B (Akt)/mammalian target
      of rapamycin (mTOR) pathway constitutive activation. Several pathway inhibitors
      were developed, including everolimus, up to the latest class of catalytic
      inhibitors such as BKM120 and BEZ235. In this review, we present some clinical
      and experimental evidence showing that the PI3K/Akt/mTOR pathway could represent
      a therapeutic target in MPNs. In in vitro studies, everolimus has been shown to
      inhibit cell proliferation and clonogenic potential in human and murine JAK2
      V617F mutated cell lines. Patients with PV and primary myelofibrosis
      hematopoietic progenitors were significantly more sensitive to everolimus
      compared with healthy control subjects. Of much interest, a combination of
      everolimus and the JAK1/2 inhibitor, ruxolitinib, showed strong synergism in
      inducing cell cycle arrest and blockade of cell proliferation. Similar data were
      obtained using a dual PI3K/mTOR inhibitor, BEZ235, with activity that was also
      shown in preclinical murine models. A multicenter phase I/II trial with
      everolimus in myelofibrosis documented a well tolerated clinical efficiency in
      terms of spleen size reduction and resolution of systemic symptoms and pruritus.
      These observations indicate that the PI3K/Akt/mTOR pathway might represent a
      novel target for treatment in MPN. The synergism demonstrated in vitro with JAK2
      inhibitors could open additional therapeutic possibilities based on concurrent
      targeting of different pathways that might optimize efficacy and reduce toxicity
      in patients.

PMID- 24290219
TI  - Allogeneic stem cell transplantation and targeted immunotherapy for multiple
      myeloma.
AB  - Multiple myeloma (MM) is a life-threatening hematological malignancy. The graft
      vs. myeloma effect is the basis of immunological strategies for treatment of MM.
      Autologous stem cell transplantation causes effective cytoreduction, but most
      patients subsequently relapse. Allogeneic stem cell transplantation (alloSCT)
      causes durable responses. The antitumour immunity mediated by lymphocytes of the
      donor achieves complete remission (CR) and molecular CR for 50% of patients with
      a long-term freedom from the disease and a cure for 20% to 25% of patients. Early
      attempts using myeloablative conditioning suffered from high, up to 50%, TRM.
      With a reduction of the toxicity of the conditioning and introduction of
      approaches applying reduced intensity conditioning, the results for alloSCT
      improved. However, they are still deficient because of continued disease
      progression and relapse after transplantation. Intense research effort
      concentrates on developing strategies to minimize remission and prevent relapse
      of MM after alloSCT. This review surveys the results of ongoing and recently
      published clinical trials. It also includes aspects of immunotherapy in
      combination with stem cell transplantation. 

PMID- 24290218
TI  - Novel treatment options for Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM), first described by Jan Waldenstrom in 1944,
      is a lymphoplasmacytic lymphoma characterized by the presence of an
      immunoglobulin M monoclonal gammopathy in the blood and monoclonal small
      lymphocytes and lymphoplasmacytoid cells in the bone marrow. WM is a rare and
      indolent disease but remains incurable. In this review we discuss the
      pathogenesis of WM and focus on novel treatment options that target pathways
      deregulated in this disease. Recent studies have helped us identify specific
      genetic mutations that are commonly seen in WM and might prove to be important
      therapeutic targets in the future. We discuss the role of epigenetics and the
      changes in the bone marrow microenvironment that are important in the
      pathogenesis of WM. The commonly used drugs are discussed with a focus on novel
      agents that are currently being used as single agents or in combination to treat
      WM. We finally focus on some agents that have shown preclinical efficacy and
      might be available in the near future. 

PMID- 24290220
TI  - Role of consolidation/maintenance therapy in multiple myeloma.
AB  - Multiple myeloma is a highly treatable but still incurable malignancy. Many
      advances have been made in the treatment of this disease, particularly thanks to
      the introduction of the immunomodulatory drugs, thalidomide and lenalidomide, and
      the proteasome inhibitor, bortezomib. Different trials have supported the
      inclusion of consolidation/maintenance therapy as part of a sequential approach
      after induction therapy and transplantation (for eligible patients). This
      therapeutic strategy aims to maintain or even improve response obtained after
      induction, and ultimately to prolong survival. The role of
      consolidation/maintenance therapy has been assessed in patients eligible and
      ineligible for transplantation, and proved to be a valuable option. The improved
      outcome reported with consolidation/maintenance therapy should, however, be
      balanced against the toxicity profile of such an approach. Prolonged exposure to
      a drug might in fact increase toxicity, and prompt management of adverse events
      is necessary. 

PMID- 24290222
TI  - Cumulative summation (CUSUM) charts in the monitoring of hypospadias outcomes: a
      tool for quality improvement initiative.
AB  - OBJECTIVE: Cumulative summation (CUSUM) charting is a statistical tool that
      allows an individual surgeon or surgical department to monitor any binary outcome
      and rapidly detect when complications are outside the acceptable limits. We
      applied CUSUM statistical analysis to hypospadias repair to utilize the results
      in our own quality Improvement process. MATERIALS AND METHODS: An institutional
      review board-approved retrospective review of all patients who underwent
      hypospadias repair by a single fellowship trained pediatric urologist at a single
      institution between September 2004 to July 2009 was performed. To graphically
      represent the complication rates and to assess for unacceptable rates, the use of
      CUSUM control charting was employed. RESULTS: In our retrospective review, there
      were a total of 184 patients who underwent a total of 203 surgeries. Using CUSUM
      analysis, our incidence of major complications was within acceptable limits until
      approximately the first 150 operations had been performed, at which time the
      complication rate fell below the lower limit, indicating performance exceeded
      expectations. CONCLUSION: CUSUM statistical charting was successfully applied to
      the retrospective monitoring of hypospadias outcomes at our institution. This is
      the first known publication in which CUSUM charts were used to evaluate
      complications of hypospadias repair.

PMID- 24290221
TI  - Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma.
AB  - BACKGROUND: SGI-1776 is a small-molecule Pim kinase inhibitor that primarily
      targets c-MYC-driven transcription and cap-dependent translation in mantle cell
      lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent
      approved for use in B-cell lymphoma that is known to induce DNA damage and
      initiate response to repair. MATERIALS AND METHODS: Our studies were conducted in
      MCL cell lines JeKo-1 and Mino, as well as primary B-cell lymphoma samples of MCL
      and splenic marginal zone lymphoma (SMZL), where we treated cells with SGI-1776
      and bendamustine. We measured levels of cellular apoptosis, macromolecule
      synthesis inhibition, and DNA damage induced by drug treatments. RESULTS: Both
      SGI-1776 and bendamustine effectively induced apoptosis as single agents, and
      when used in combination, an additive effect in cell killing was observed in MCL
      cell lines JeKo-1 and Mino, as well as in MCL and SMZL primary cells. As
      expected, SGI-1776 was effective in inducing a decrease of global RNA and protein
      synthesis, and bendamustine significantly inhibited DNA synthesis and generated a
      DNA damage response. When used in combination, the effects were intensified in
      DNA, RNA, and protein synthesis inhibition compared with single-agent treatments.
      CONCLUSION: These data provide a foundation and suggest the feasibility of using
      Pim kinase inhibitors in combination with chemotherapeutic agents such as
      bendamustine in B-cell lymphoma.

PMID- 24290223
TI  - Analysis of uroflow patterns in children with dysfunctional voiding.
AB  - OBJECTIVE: Although a staccato uroflow pattern is considered representative of
      dysfunctional voiding (DV), we recently found that only a third of children with
      staccato flow had an active pelvic floor electromyography (EMG) during voiding.
      Here, we analyzed the reverse, that is, how often a staccato flow pattern occurs
      in children with documented DV. In addition, we reviewed what other flow patterns
      are prevalent in this condition. MATERIALS AND METHODS: We reviewed our LUT
      dysfunction registry for children with EMG-confirmed DV. Uroflow patterns were
      categorized as staccato, interrupted, mixed (i.e., staccato and interrupted
      patterns), or grossly normal. RESULTS: Of 596 children who underwent a
      uroflow/EMG examination, 121 had an active pelvic floor EMG during voiding, that
      is a finding consistent with the diagnosis of DV. The flow patterns identified in
      those diagnosed with DV were staccato in 70 (58%), interrupted in 22 (19%), mixed
      in 12 (10%), and a bell-shaped or depressed curve in 17 (14%). Staccato pattern
      became normal in 96% following successful treatment with biofeedback.
      CONCLUSIONS: While a staccato uroflow pattern was the most common pattern seen in
      children diagnosed with DV by a uroflow/EMG, nearly a third had an interrupted or
      mixed flow pattern underscoring the importance of performing simultaneous pelvic
      floor EMG during a uroflow study, especially when trying to rule out DV. Failure
      of the staccato flow pattern to normalize after therapy strongly suggests either
      inadequate therapy or an incorrect diagnosis.

PMID- 24290224
TI  - Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary
      tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux).
AB  - OBJECTIVE: There has been hesitancy to use dextranomer/hyaluronic acid copolymer
      (DHXA, Deflux for vesicoureteral reflux (VUR) in the setting of lower urinary
      tract (LUT) dysfunction because of the limited number of published studies, the
      possibility of less success, and the manufacturer's recommendations
      contraindicating its use in patients with active LUT dysfunction. We report on
      our experience using DXHA in this subset of patients whose VUR persisted despite
      targeted therapy for their LUT condition. MATERIALS AND METHODS: We reviewed
      patients diagnosed with both a LUT condition and VUR who underwent subureteric
      DXHA while still undergoing treatment for their LUT dysfunction. Persistence of
      VUR was confirmed by videourodynamic studies (VUDS)/VCUG (voiding
      cystourethrogram) and all patients were on targeted treatment (TT) and antibiotic
      prophylaxis prior to and during DXHA injection. VUR was reassessed post
      injection. RESULTS: Fifteen patients (22 ureters; 21F,1M) met inclusion criteria
      (mean age 6.1 years, range 4-12). Following one to three DXHA injections, VUR
      resolved in 17 ureters (77%) including eight of nine ureters in dysfunctional
      voiding (DV) patients, five of nine in idiopathic detrusor overactivity disorder
      (IDOD), and four of four in detrusor underutilization disorder (DUD) patients.
      CONCLUSIONS: DXHA is safe and effective in resolving VUR in children with
      associated LUT dysfunction, even before their LUT condition has fully resolved.
      Highest resolution rates were noted in patients with either DV or DUD or who were
      least symptomatic prior to injection.

PMID- 24290225
TI  - Design of experiment approach for the optimization of polybrominated diphenyl
      ethers determination in fine airborne particulate matter by microwave-assisted
      extraction and gas chromatography coupled to tandem mass spectrometry.
AB  - A sensitive and selective procedure for the determination of 12 polybrominated
      diphenyl ethers (BDE-28, BDE-49, BDE-47, BDE-66, BDE-100, BDE-119, BDE-99, BDE
      155, BDE-154, BDE-153, BDE-139 and BDE-183) in airbone particulate matter (PM2.5)
      at trace level has been developed. The proposed method includes extraction PM2.5
      bound PBDEs by microwave-assisted extraction (MAE) followed by gel permeation
      chromatography (GPC) clean-up and determination by GC-MS/MS using a programmed
      temperature vaporizer (PTV) in large volume injection (LVI) mode to introduce the
      sample to the chromatographic system. A design of experiment (DoE) approach was
      used for the optimization of large volume injection and microwave-assisted
      extraction parameters to improve these techniques efficiency. Other conditions of
      the method were studied: GC-MS/MS parameters, extraction solvent and matrix
      effect. The limit of quantification ranged from 0.063pgm(-3) to 0.210pgm(-3) when
      air volumes of 723m(3) were collected. Recoveries ranged from 80% to 106%. The
      method was successfully applied to eight real samples collected from a
      residential area of the monitoring network of the Region of Valencia Government
      (Spain) during April-August 2012. BDE-47 and BDE-99 were quantified in six and
      five samples respectively. The concentrations were ranged from 0.063 to 0.112pgm(
      3) for BDE-47, and from 0.107 to 0.212pgm(-3) for BDE-99. 

PMID- 24290226
TI  - The prolongation of length of stay because of Clostridium difficile infection.
AB  - BACKGROUND: Clostridium difficile infection (CDI) possibly extends hospital
      length of stay (LOS); however, the current evidence does not account for the time
      dependent bias, ie, when infection is incorrectly analyzed as a baseline
      covariate. The aim of this study was to determine whether CDI increases LOS after
      managing this bias. METHODS: We examined the estimated extra LOS because of CDI
      using a multistate model. Data from all persons hospitalized >48 hours over 4
      years in a tertiary hospital in Australia were analyzed. Persons with health care
      associated CDIs were identified. Cox proportional hazards models were applied
      together with multistate modeling. RESULTS: One hundred fifty-eight of 58,942
      admissions examined had CDI. The mean extra LOS because of infection was 0.9 days
      (95% confidence interval: -1.8 to 3.6 days, P = .51) when a multistate model was
      applied. The hazard of discharge was lower in persons who had CDI (adjusted
      hazard ratio, 0.42; P < .001) when a Cox proportional hazard model was applied.
      CONCLUSION: This study is the first to use multistate models to determine the
      extra LOS because of CDI. Results suggest CDI does not significantly contribute
      to hospital LOS, contradicting findings published elsewhere. Conversely, when
      methods prone to result in time-dependent bias were applied to the data, the
      hazard of discharge significantly increased. These findings contribute to
      discussion on methods used to evaluate LOS and health care-associated infections.

PMID- 24290227
TI  - Evaluation of PET radioligands for in vivo visualization of phosphodiesterase 5
      (PDE5).
AB  - INTRODUCTION: The cyclic guanosine monophosphate (cGMP) specific
      phosphodiesterase type 5 (PDE5) is considered to play an important role in
      various etiologies such as pulmonary arterial hypertension (PAH) and chronic
      heart failure. This PDE5 modulation represents an important prognostic and/or
      therapeutic target; however, there is currently no method to non-invasively
      evaluate the PDE5 expression levels in vivo. METHODS: Radiolabeled tracers were
      prepared by N-alkylation of the corresponding precursors with [(11)C]methyl
      trifluoromethanesulfonate ([(11)C]CH3OTf) or 2-[(18)F]fluoroethyl
      trifluoromethanesulfonate ([(18)F]FEtOTf). Biodistribution of radiolabeled
      tracers was studied in NMRI mice and their specific binding to PDE5 was
      investigated by comparing their lung retention as the enzyme is abundantly
      expressed in this organ. RESULTS: The overall radiochemical yields ranged between
      24% and 60% for labeled radiotracers with radiochemical purity of>99%. The
      highest retention in the lungs at 30min post injection was observed for
      vardenafil derivatives [(11)C]-7 and [(18)F]-11 and the retention of the
      ethoxyethyl pyrazolopyrimidine derivative [(11)C]-37 was moderate. The other
      investigated compounds [(11)C]-8, [(11)C]-14, [(11)C]-21 and [(11)C]-33 showed
      lower retention in lungs in agreement with their lower in-vitro affinity for
      PDE5. CONCLUSION: Among the different radiolabeled PDE5 inhibitors evaluated in
      this study, the vardenafil derivatives [(11)C]-7 and [(18)F]-11 are found to be
      promising tracers for in vivo visualization of PDE5.

PMID- 24290228
TI  - Surface passivation of undoped hematite nanorod arrays via aqueous solution
      growth for improved photoelectrochemical water splitting.
AB  - A facile solution-based strategy was found to be effective for surface
      passivation of undoped hematite nanorod photoanodes by adding noble-metal
      chlorides such as HAuCl4 and H2PtCl6 in the Fe(3+) precursor solution. XPS and
      Raman spectra revealed that noble-metal ions would not be doped into, but lead to
      surface disorder of hematite. Incident photon to current efficiency (IPCE) of the
      hematite photoanode grown in HAuCl4 and H2PtCl6 contained precursor solution was
      increased from 3.6% to 11.5% and 12.9%, respectively, at 365 nm and 1.23 V vs.
      RHE (reversible hydrogen electrode). This photoelectrochemical (PEC) enhancement
      was ascribed to the surface passivation, which resulted in a reduced
      recombination of photogenerated carriers, as confirmed by ultrafast transient
      absorption spectroscopy.

PMID- 24290229
TI  - Fabrication, characterization and screen printing of conductive ink based on
      carbon@Ag core-shell nanoparticles.
AB  - The large-scale synthesis and characterization of carbon-core/Ag-shell (C@Ag)
      nanoparticles by the successive reduction of silver ammonia are described. The
      resultant C@Ag nanoparticles had a mean core diameter of 360 nm and a
      controllable shell thickness from 10 to 40 nm by simple adjustments of repeat
      coating times. Various analysis techniques confirmed that the carbon cores were
      fully covered by Ag nanoshells. The results also show that C/Ag composite
      nanomaterials-based conductive inks, which can be easily produced on a large
      scale and possess outstanding electronic properties, have great potential for the
      convenient fabrication of flexible and low-cost carbon-based electronic devices
      and replace the traditional pure silver paste, by using a simple screen printing
      technique.

PMID- 24290230
TI  - Oxidative modification of blood serum proteins in multiple sclerosis after
      interferon or mitoxantrone treatment.
AB  - This study was aimed at (i) comparison of the usefulness of serum protein
      oxidation parameters for assessment of oxidative stress (OS) in multiple
      sclerosis (MS), and (ii) comparison of OS in MS patients subject to various
      therapies. Elevated glycophore level was noted in relapsing-remitting (RRMS)
      patients without treatment and patients treated with interferons beta1a and
      beta1b (10.33+/-3.27, 8.02+/-2.22 and 8.56+/-2.45 vs control 5.27+/-0.73
      fluorescence units (FU)/mg protein). Advanced oxidation protein products (295+/
      135 vs 83+/-65nmol/mg protein), carbonyl groups (3.68+/-1.44nmol/mg protein vs
      2.03+/-0.23nmol/mg protein), kynurenine (7.71+/-0.1.67 vs 5.5+/-0.63 FU/mg
      protein) and N'-formylkynurenine (7.69+/-0.7 vs 4.97+/-0.59 FU/mg protein) levels
      were increased, while thioredoxin level was decreased in RRMS patients without
      treatment (5.03+/-2.18 vs 10.83+/-2.75ng/ml) with respect to control. The level
      of OS was higher in untreated RRMS patients and in SPMS patients treated with
      mitoxantrone than in patients treated with interferon. 

PMID- 24290231
TI  - Concomitant tibial shaft and posterior malleolar fractures can be readily
      diagnosed from plain radiographs: A retrospective study.
AB  - BACKGROUND: Concomitant tibial shaft and posterior malleolar fractures (PMFs) are
      often encountered in clinical settings. Plain films were reviewed for concomitant
      PMF, and fracture patterns were analyzed by focusing on the integrity of the
      fibula and the location of the fibular fracture. METHODS: A retrospective review
      of patients who presented with tibial shaft fractures between January 2005 and
      January 2010 was performed. Patients were included if they were at least 18 years
      of age and had a tibial diaphyseal fracture. Exclusion criteria were age less
      than 18 years, previous surgery on the same leg, and pathological fractures.
      Medical records were reviewed for information on injury mechanisms. Pre- and post
      operative radiographs were analyzed for PMFs, tibial fracture pattern, fibular
      integrity, fibular fracture pattern, treatment type, and time to fracture union.
      Descriptive statistical tests were used. RESULTS: Among 240 patients, there were
      20 cases (15 male and 5 female) of concomitant PMF, all detected in lateral
      radiograph views. The incidence of PMF was 8.3%. Most patients had a motorcycle
      injury (n = 15, 75%). Distal tibia spiral fracture was the most common fracture
      pattern (85%) and there was no proximal tibia fracture (0%). Combined fibular
      fractures were found in 17 patients (85%). There were nine proximal fibular
      fractures (45%). Intact fibulas were found in three patients (15%). Only one PMF
      was treated with screw fixation. All PMFs showed radiographic evidence of healing
      within 5 months post-operatively. CONCLUSION: We recommend careful radiographic
      examination to evaluate PMF, especially in patients with distal tibial spiral
      fractures combined with proximal fibular fractures or intact fibulas.

PMID- 24290233
TI  - Impacts of extreme weather on the health and well-being of people who are
      homeless.
AB  - This letter responds to the article by Cusack et al., 'Extreme weather-related
      health needs of people who are homeless' (Australian Journal of Primary Health,
      2013, 19(3), 250-255), which addressed the impacts of extreme weather on the
      health of the homeless population in inner city Adelaide. We compare the findings
      of Cusack et al. to our own original research, based on interviews with service
      providers to the homeless in urban and rural Victoria. We further place this
      issue in the broader context of climate change, which is crucial given the
      expected increase in extreme weather events and associated health impacts. 

PMID- 24290232
TI  - Comparison of proficiency in an anesthesiology course across distinct medical
      student cohorts: psychometric approaches to test equating.
AB  - BACKGROUND: Examinations are necessary for assessment of student proficiency in
      medical education, but comparison of achievement across different cohorts in
      different tests is challenging. We applied psychometric test equating methods to
      compare student proficiency in two different examinations for a clinical
      anesthesiology course. METHODS: Each examination contained 50 multiple choice
      items and nine common items were identified from the two examinations
      (administered in 2011 and 2012). The common item design was used for test
      equating. Two psychometric test-equating approaches, chained linear equating and
      item response theory, were used to compare student proficiency in anesthesiology
      across distinct medical student cohorts. Raw scores from the 2012 test were
      linearly transformed to the 2011 scale using the chained method, and then Rasch
      analysis was applied to calibrate examinee ability and item difficulty in the two
      examinations on a common scale. RESULTS: Both the linear equating method and
      Rasch analysis indicated that students in the 2011 examination performed better
      than those who took the 2012 examination (both p < 0.001). Rasch analysis
      revealed that the range of student ability was between -0.53 and 4.16, while the
      difficulty of all items ranged from -5.25 to 6.32. No significant difference in
      mean item difficulty was noted among the common items and other items in the two
      examinations. CONCLUSION: Although both the chained linear equating method and
      Rasch analysis can be readily applied to practical test-equating issues in
      medical education, Rasch analysis exhibited more versatility in test parameter
      estimation and item bank development for clinical curriculums.

PMID- 24290234
TI  - A passive movement method for parameter estimation of a musculo-skeletal arm
      model incorporating a modified hill muscle model.
AB  - In this paper we present an experimental method of parameterising the passive
      mechanical characteristics of the bicep and tricep muscles in vivo, by fitting
      the dynamics of a two muscle arm model incorporating anatomically meaningful and
      structurally identifiable modified Hill muscle models to measured elbow
      movements. Measurements of the passive flexion and extension of the elbow joint
      were obtained using 3D motion capture, from which the elbow angle trajectories
      were determined and used to obtain the spring constants and damping coefficients
      in the model through parameter estimation. Four healthy subjects were used in the
      experiments. Anatomical lengths and moment of inertia values of the subjects were
      determined by direct measurement and calculation. There was good reproducibility
      in the measured arm movement between trials, and similar joint angle trajectory
      characteristics were seen between subjects. Each subject had their own set of
      fitted parameter values determined and the results showed good agreement between
      measured and simulated data. The average fitted muscle parallel spring constant
      across all subjects was 143 N/m and the average fitted muscle parallel damping
      constant was 1.73 Ns/m. The passive movement method was proven to be successful,
      and can be applied to other joints in the human body, where muscles with similar
      actions are grouped together.

PMID- 24290235
TI  - Assessing resistance of ivermectin and moxidectin against nematodes in cattle
      naturally infected using three different methodologies.
AB  - The objective of this study was to evaluate the accuracy of the faecal egg count
      reduction test (FECRT) and the faecal egg count efficacy test (FECET) to assess
      the resistance status of ivermectin (630 MUg/kg) and moxidectin (200 MUg/kg),
      using the controlled efficacy test as a reference, and whether the results of the
      EPG are equivalent to the efficacy results from the parasitological necropsies.
      Two experiments were conducted. The results demonstrate that it was not possible
      to demonstrate that the EPG values were equivalent with the ivermectin and
      moxidectin efficacy obtained by parasitological necropsies, mainly if the
      phenomenon of parasites resistance is not advanced in a determined field
      population. Maybe the FECET technique would be possibly better than the FECRT.
      The high anthelmintic efficacy of 200 MUg/kg moxidectin, in naturally infected
      cattle, against field population of nematodes that are resistant to 630 MUg/kg
      ivermectin, was observed in this study.

PMID- 24290236
TI  - Staphylococcus aureus chronic intramammary infection modifies protein expression
      of transforming growth factor beta (TGF-beta) subfamily components during active
      involution.
AB  - The objectives of this study were to determine whether Staphylococcus aureus
      chronic intramammary infection (IMI) influences protein expression of TGF-beta
      subfamily components and collagen I and to examine the histomorphometric changes
      that occur in mammary stroma and parenchyma during active mammary gland
      involution. Twenty-one Holstein non-pregnant cows in late lactation either
      uninfected or with chronic natural S. aureus IMI were included in this study.
      Cows were slaughtered at 7, 14 and 21d after cessation of milking and samples for
      immunohistochemical and morphometric analysis were taken. Protein expression of
      TGF-beta1, TGF-beta2 and TGF-beta3 was significantly higher in chronically
      infected quarters than in uninfected controls at the three involution stages
      studied. Immunostaining of TGF-betaR1 and TGF-betaR3 and collagen I was
      significantly higher in S. aureus-infected quarters than in uninfected controls
      at every involution time evaluated. The percentages of tissue area composed of
      parenchyma and intralobular stroma were significantly higher in S. aureus
      infected than in uninfected quarters. Chronic S. aureus mastitis modifies protein
      expression of the three TGF-beta isoforms and type 1 and 3 receptors, which was
      associated with changes directed to limit the scope of inflammation and injury to
      the host. 

PMID- 24290237
TI  - Assessing a nurse-led advance directive and advance care planning seminar.
AB  - BACKGROUND: Advance directives (AD) and advance care planning (ACP) are critical
      to making patient-centered end-of-life decisions. Despite their importance,
      completion rates for AD in the United States remain low at about 18-36%. Lack of
      education related to AD and not understanding AD have been cited as key reasons
      for not participating in ACP or completing AD. PURPOSE: The purpose of this quasi
      experimental pilot study was to assess the effectiveness of a nurse led
      educational AD seminar that used the Five Wishes on attitudes related to AD, AD
      completion, and participation in ACP conversations. METHODS: A post-test repeated
      measures design was used. RESULTS: Of the 86 participants who attended the
      seminar, most (n=71, 82.6%) found the seminar useful, and 97.7% (n=84) reported
      that they were likely to complete an AD and participate in ACP conversations with
      family or friends. Overall attitudes about ADs were high. Older females were more
      likely to complete AD than their younger male counterparts, and women were more
      likely than men to have ACP conversations. CONCLUSION: The results of this study
      lend support to the role of nursing-driven community-based educational
      interventions to improve AD completion and participation in the ACP process.

PMID- 24290238
TI  - Motion management for radical radiotherapy in non-small cell lung cancer.
AB  - Intrafraction tumour motion is an issue that is of increased interest in the era
      of image-guided radiotherapy. It is particularly relevant for non-small cell lung
      cancer, for which a number of recent developments are in use to aid with motion
      management in the delivery of radical radiotherapy. The ability to deliver
      hypofractionated ablative doses, such as in stereotactic radiotherapy, has been
      aided by improvements in the ability to analyse tumour motion and amend treatment
      delivery. In addition, accounting for tumour motion can enable dose escalation to
      occur by reducing the normal tissue being irradiated by virtue of a reduction in
      target volumes. Motion management for lung tumours incorporates five key
      components: imaging, breath-hold techniques, abdominal compression, respiratory
      tracking and respiratory gating. These will be described, together with the
      relevant benefits and associated complexities. Many studies have described
      improved dosimetric coverage and reduced normal tissue complication probability
      rates when using motion management techniques. Despite the widespread uptake of
      many of these techniques, there is a paucity of literature reporting improved
      outcome in overall survival and local control for patients whenever motion
      management techniques are used. This overview will review the extent of lung
      tumour motion, ways in which motion is detected and summarise the key methods
      used in motion management. 

PMID- 24290239
TI  - Ethical issues relating to the inclusion of relatives as clients in the post
      stroke rehabilitation process as perceived by patients, relatives and health
      professionals.
AB  - OBJECTIVE: To document the ethical issues regarding the systematic inclusion of
      relatives as clients in the post-stroke rehabilitation process. METHODS: A two
      phase qualitative design consisting of in-depth interviews with relatives and
      stroke-clients (Phase 1) and three focus groups with relatives, stroke-clients
      and health professionals (Phase 2). Data was audio recorded. Transcribed
      interviews and focus groups content were rigorously analyzed by two team members.
      RESULTS: The interview sample was composed of 25 relatives and of 16 individuals
      with a first stroke whereas the three focus group sample size varied from 5 to 7
      participants. Four main themes emerged: (1) overemphasis of caregiving role with
      an unclear legitimacy of relative to also be a client; (2) communication as a key
      issue to foster respect and a family-centered approach; (3) availability and
      attitudes of health professionals as a facilitator or a barrier to a family
      centered approach; and (4) constant presence of relatives as a protective factor
      or creating a perverse effect. CONCLUSION/PRACTICE IMPLICATIONS: The needs of
      relatives are well known. The next step is to legitimize their right to receive
      services and to acknowledge the combined clinical and ethical value of including
      them post-stroke. Interdisciplinary health care approaches and communication
      skills should be addressed.

PMID- 24290240
TI  - The Massachusetts BMI letter: a qualitative study of responses from parents of
      obese children.
AB  - OBJECTIVES: Massachusetts (MA) public schools conduct mandated body-mass index
      (BMI) screening and until recently, communicated results in a letter to
      parents/caregivers, to encourage primary care visits and provide aggregate data
      to the state Department of Public Health. This study assessed the letter's
      readability and qualitatively explored parents' responses to it. METHODS:
      Readability of the BMI letter was calculated. Audio-taped 1-h focus groups were
      conducted with parents/caregivers of 8- to 14-year-old obese (>=95th BMI-for-age
      percentile) children. A semi-structured interview guide was used to elicit
      responses. Qualitative content analysis was conducted on transcripts to identify
      emergent themes. RESULTS: Readability analysis showed higher grade levels than
      recommended. Eight focus groups consisting of two to six parents each were
      conducted (n=29); 83% were female, mean age 41+/-9years, and 65% self-identified
      as Hispanic/Latino. Key themes identified included usefulness of the BMI letter,
      concerns about utility of BMI for screening, concerns about impacting self
      esteem, and failure to understand the letter. CONCLUSIONS: The MA BMI letter may
      not have been achieving its desired goal with some parents. PRACTICE
      IMPLICATIONS: Emergent themes from this study could be used to test effectiveness
      of similar BMI letters nationwide and develop strategies to improve communication
      to parents.

PMID- 24290241
TI  - Psychosocial services for couples in infertility treatment: what do couples
      really want?
AB  - OBJECTIVES: To describe the psychosocial supports that infertile couples desire
      to help cope with infertility-related distress, which psychosocial services they
      sought, and the benefits and drawbacks of these services. METHODS: Qualitative
      interview study with 32 heterosexual infertile couples seeking infertility
      treatment. Maximum variation sampling was used; data were analyzed using thematic
      analysis. RESULTS: Most couples desired psychosocial support, but only half of
      the sample sought support. Some couples met with psychologists for help with
      relationship conflict and coping strategies. Participants suggested peer
      mentoring to fulfill needs for coping, shared experience, and guidance through
      the treatment process. Couples also desired written information about practical
      and emotional aspects of treatment. Negative attitudes toward psychological
      counseling and a lack of information about support services prevented some
      couples from seeking support. CONCLUSIONS: Infertile couples expressed numerous
      needs for psychosocial supports, but often felt that supports were not available.
      A variety of services should be offered in order to fulfill patients' varied
      needs. PRACTICE IMPLICATIONS: Awareness of the reasons why patients desire
      psychosocial services will help clinicians to refer patients to currently
      available psychosocial supports, and will aid in the development of appropriate
      supports, including couples counseling, peer mentoring, and written information
      in lay language.

PMID- 24290242
TI  - Readability, suitability and comprehensibility in patient education materials for
      Swedish patients with colorectal cancer undergoing elective surgery: a mixed
      method design.
AB  - OBJECTIVE: To characterize education materials provided to patients undergoing
      colorectal cancer surgery to gain a better understanding of how to design
      readable, suitable, comprehensible materials. METHOD: Mixed method design.
      Deductive quantitative analysis using a validated suitability and
      comprehensibility assessment instrument (SAM+CAM) was applied to patient
      education materials from 27 Swedish hospitals, supplemented by language
      technology analysis and deductive and inductive analysis of data from focus
      groups involving 15 former patients. RESULTS: Of 125 patient education materials
      used during the colorectal cancer surgery process, 13.6% were rated 'not
      suitable', 76.8% 'adequate' and 9.6% 'superior'. Professionally developed stoma
      care brochures were rated 'superior' and 44% of discharge brochures were 'not
      suitable'. Language technology analysis showed that up to 29% of materials were
      difficult to comprehend. Focus group analysis revealed additional areas that
      needed to be included in patient education materials: general and personal care,
      personal implications, internet, significant others, accessibility to healthcare,
      usability, trustworthiness and patient support groups. CONCLUSION: Most of the
      patient education materials were rated 'adequate' but did not meet the
      information needs of patients entirely. Discharge brochures particularly require
      improvement. PRACTICE IMPLICATIONS: Using patients' knowledge and integrating
      manual and automated methods could result in more appropriate patient education
      materials.

PMID- 24290243
TI  - How are the English Stop Smoking Services responding to growth in use of
      electronic cigarettes?
AB  - OBJECTIVE: To assess extent of electronic cigarette use by smokers attending Stop
      Smoking Services, the advice given about electronic cigarettes and whether this
      usage is recorded. METHODS: Fifty-eight managers and 1284 practitioners completed
      an online survey. Questions covered use of electronic cigarettes, the advice
      given and whether use was recorded in client databases. RESULTS: Ninety per cent
      (n=1150) and 95% (n=1215) of practitioners respectively, reported that their
      clients were using electronic cigarettes and that they had been asked about them.
      Seventy-one per cent (n=41) of managers reported that they had a policy on the
      advice to be given; of whom 85% (n=35) said that practitioners should say that
      products were unlicensed. Fifty-five per cent (n=707) of practitioners reported
      giving such advice and 11% (n=138) said they warned smokers about their safety.
      Only 9% (n=119) reported that they recorded clients' use. CONCLUSION: Although
      use of electronic cigarettes by smokers in Stop Smoking Services is common, few
      provisions are in place to record their use. Practitioners mostly advise that
      products are not licensed. PRACTICAL IMPLICATIONS: There is a need to consider
      additional training for practitioners on use of e-cigarettes and harm reduction
      generally to ensure that advice is consistent and evidence-based.

PMID- 24290244
TI  - Risk of stroke in long-term dialysis patients compared with the general
      population.
AB  - BACKGROUND: Patients undergoing maintenance dialysis are at increased risk of
      stroke. STUDY DESIGN: We performed a nationwide retrospective cohort study to
      determine the risks for ischemic stroke and hemorrhagic stroke among incident
      hemodialysis (HD) and peritoneal dialysis (PD) patients in comparison to a
      reference group in Taiwan. SETTING & PARTICIPANTS: Data for 74,192 HD patients,
      5,974 PD patients, and 669,773 nondialysis individuals who were older than 18
      years and had no history of stroke or cancer were retrieved from the National
      Health Insurance Research Database for 1998-2009. PREDICTORS: Patient
      demographics, comorbid conditions. OUTCOME: First hospitalization for stroke,
      defined as a diagnosis at discharge (either primary or 1 of 4 secondary
      diagnoses) of ischemic or hemorrhagic stroke using International Classification
      of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: HD and PD
      patients had higher incidences of hospitalized ischemic stroke (102.6 and
      100.1/10,000 person-years) and hemorrhagic stroke (74.7 and 59.4/10,000 person
      years) in comparison to the age- and sex-matched reference cohort (42.4 and
      13.0/10,000 person-years, respectively). In addition to HD and PD therapy, older
      age, male sex, diabetes, and hypertension were found to be independent risk
      factors for both ischemic and hemorrhagic strokes. Using the HD group as the
      comparison group, we found that PD patients had a lower risk of hemorrhagic
      stroke (HR, 0.75; 95% CI, 0.58-0.96), and there was no significant difference in
      risks of ischemic stroke between PD and HD patients after adjusting for all
      potential confounders and competing risk of death, and matched by propensity
      scores. LIMITATIONS: This was a retrospective study, and some important variables
      were not available. CONCLUSIONS: Patients undergoing dialysis are at elevated
      risk of stroke. Patients undergoing PD appear to be less likely to develop
      hemorrhagic stroke than those undergoing HD. Comprehensive control of
      hypertension and diabetes is necessary when delivering dialysis treatment.

PMID- 24290245
TI  - Skin involvement in atypical hemolytic uremic syndrome.
AB  - Skin involvement in atypical hemolytic uremic syndrome (aHUS) is very uncommon
      and therefore often unrecognized as a specific symptom of aHUS. We describe 3
      cases of patients with aHUS who developed skin lesions that completely recovered
      when disease-specific treatment was established. These cases suggest that in
      individuals with aHUS, when skin lesions of unknown origin occur, the possibility
      that they are due to thrombotic microangiopathy should be considered. 

PMID- 24290246
TI  - Acute kidney injury from cherry concentrate in a patient with CKD.
AB  - Nutraceuticals are supplements and medical foods that offer numerous health
      benefits. However, these substances may have adverse effects on multiple organ
      systems, leading to significant morbidity. I present a patient with chronic
      kidney disease who experienced hemodynamically mediated acute kidney injury and
      hyperkalemia after daily consumption of cherry concentrate. The method of injury
      was most likely cyclooxygenase inhibition by the compounds in cherries that mimic
      the mechanism of action of nonsteroidal anti-inflammatory medications. Ceasing
      cherry concentrate consumption led to improvements in both the patient's
      hyperkalemia and kidney injury. Physicians should be aware of the potentially
      harmful side effects of cherry concentrate and approach the use of cherry extract
      or concentrate with caution in patients with underlying kidney disease.

PMID- 24290247
TI  - Clinical and histological outcomes following living-related liver transplantation
      in children.
AB  - OBJECTIVES: Living-related liver transplantation (LRLT) was developed to increase
      the donor pool of size-matched organs for children. In the UK only one centre
      performed LRLT between 1993 and 2008. This study reports the clinical and
      histological outcomes following adult-to-paediatric LRLT at our centre. METHODS:
      Forty-six LRLTs were reviewed. Recipients had a mean age, weight and PELD score
      of 2.4years (range 0.5-11years), 11.0kg (3.7-32.3kg) and 11.7 (-20.3 to 49.1)
      respectively. The incidence of post-transplant paediatric morbidity, abnormal
      liver function tests and histological abnormalities was reviewed. RESULTS:
      Patient and graft survival rates were 97.8%, 95.1% and 95.1%, and 97.8%, 92.1%
      and 71.7% at 1, 5 and 10years post-transplant respectively. Three children were
      re-transplanted at 44, 100 and 119months post-transplant. Nine children developed
      neuropsychological problems, 6 experienced educational difficulties, 5 developed
      post-transplant lymphoproliferative disorder and 5 suffered height or weight
      growth<2 centile. Normal LFTs were found in 41.7%, 50%, 68% and 64.7% of children
      at median follow-up of 6, 13, 61 and 85months respectively. Liver histology
      showed hepatitis, acute rejection, non-specific changes, biliary pathology,
      vascular pathology and chronic rejection in 32.9%, 29.5%, 13.4%, 10.1%, 6% and 2%
      of biopsies respectively. CONCLUSIONS: The prevalence of paediatric morbidity and
      histological abnormalities emphasize the need for specialist and long-term follow
      up following LRLT in children.

PMID- 24290248
TI  - Racial disparities in children's blood lead levels: possible implication of
      divalent metal transporter 1.
AB  - Adverse effects of lead exposure at low-dose (<10 MUg/dL) in children showed a
      growing interest over the last decades. Black ethnicity is usually associated
      with elevated blood lead levels (BLLs), independently of age and socioeconomic
      conditions. The gastrointestinal uptake of lead represents a key step in the
      process of lead kinetic and toxicity. The involvement of divalent metal
      transporter 1 (DMT1) in the lead absorption has been previously presumed and
      reported. I postulate that inter-ethnic differences in DMT1 expression may
      explain a large part of the racial disparity in children's BLLs, and suggest a
      few analyses to test this hypothesis. The hypothesis rests on some observations
      from previous researches. The inverse association between BLLs and iron intake
      has been reported in both cross-sectional and follow-up studies. It appears that
      no study specifically addressed the modifying effect of ethnicity in this
      association. Previous reports suggest that DMT1 is the primary mechanism for
      gastrointestinal iron absorption. There are four forms of DMT1 expressed in the
      enterocytes, which did not respond similarly to iron changes. It is not excluded
      that some children be more likely to uptake ingested lead depending on DMT1
      isoform expressed. I hypothesize that the expression of the more active DMT1
      isoform (+1A/+IRE) is more common in Non-Hispanic Black compared with Non
      Hispanic White children, and I suggest how to test this hypothesis. If the
      hypothesis is confirmed, this would suggest that the prevention of iron
      deficiency must be included in the primary programs for preventing increase of
      BLLs in Non-Hispanic Black children, rather than as part of secondary prevention.
      Moreover, thorough studies would be useful to characterize the interaction
      between environmental lead levels and DMT1 expression in relation to BLLs in
      young children.

PMID- 24290249
TI  - Wetting-controlled strategies: from theories to bio-inspiration.
AB  - Creatures have evolved the unique wetting-controlled strategies on their surfaces
      to collect water for the sake of survival, such as Beetle back, spider silk and
      plant leaf as well, which inspires us to open the area of novel researches. In
      this feature article, we review the theoretical basis of wetting-controlling
      regarding of wettability and highlight the biological wetting-controlled
      strategies in water transport, and water collection, and also introduce some bio
      inspired materials with water collection properties. It is significant to design
      the novel materials that would be used in the fields of responsive, smart
      catalysis, filtration and sensing besides water collection. 

PMID- 24290251
TI  - [Percutaneous ventricular restoration with Parachute].

PMID- 24290250
TI  - Patients' perspectives on antiepileptic medication: relationships between beliefs
      about medicines and adherence among patients with epilepsy in UK primary care.
AB  - BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) can result in suboptimal
      outcomes for patients. AIM: This study aimed to assess the utility of a theory
      based approach to understanding patient perspectives on AEDs and adherence.
      METHOD: Patients with epilepsy, identified by a GP case note review, were mailed
      validated questionnaires assessing their perceptions of AEDs and their adherence
      to them. RESULTS: Most (84.9%) of the 398 AED-treated respondents accepted the
      necessity of AEDs, but over half expressed doubts, with 55% disagreeing or
      uncertain about the statement 'I would prefer to take epilepsy medication than
      risk a seizure'. Over a third (36.4%) expressed strong concerns about the
      potential negative effects of AEDs. We used self-report and medication possession
      ratio to classify 36.4% of patients as nonadherent. Nonadherence was related to
      beliefs about medicines and implicit attitudes toward AEDs (p<0.05). Adherence
      related attitudes toward AEDs were correlated with general beliefs about
      pharmaceuticals (BMQ General: General Harm, General Overuse, and General Benefit
      scales) and perceptions of personal sensitivity to medicines (PSM scale).
      CONCLUSION: We identified salient, adherence-related beliefs about AEDs. Patient
      centered interventions to support medicine optimization for people with epilepsy
      should take account of these beliefs.

PMID- 24290252
TI  - Statistical or clinical improvement? Determining the minimally important
      difference for the vascular quality of life questionnaire in patients with
      critical limb ischemia.
AB  - OBJECTIVE: Interpreting whether changes in quality of life (Qol) in patients with
      peripheral arterial disease (PAD) are not only statistically significant but also
      clinically relevant, may be difficult. This study introduces the concept of the
      minimally important difference (MID) to vascular surgeons using Qol outcomes of
      patients treated for chronic critical limb ischemia (CLI). METHODS: The Vascular
      Quality of Life (VascuQol) questionnaire was recorded at baseline before
      treatment and after 6 months follow-up in consecutive patients with CLI treated
      between May 2007 and May 2010. Statistical significance of change in VascuQol
      score was tested with the Wilcoxon Signed Rank test. The MID for the VascuQol
      score was determined using a clinical anchor-based method and a distribution
      based method. RESULTS: A total of 127 patients with CLI completed the VascuQol
      after 6 months. The VascuQol sum scores improved from 3.0 (range 1.1-5.9) at
      baseline to 4.0 (range 1.2-6.7) at 6 months (p < .001). The MID on the VascuQol
      sumscore indicating a clinically important change determined with the anchor
      based method was 0.36, and with the distribution-based method was 0.48. On an
      individual level, depending on the method of determining the MID, this resulted
      in 60% to 68% of the patients with an important benefit. CONCLUSIONS: Expression
      of changes in Qol by means of the MID provides better insight into clinically
      important changes than statistical significance.

PMID- 24290253
TI  - [IV Consensus Meeting of the Spanish Society of Liver Transplantation 2012.
      Exceptions to model for end-stage liver disease in prioritizing liver
      transplantation].

PMID- 24290254
TI  - Three-dimensional facial distances of Northern Sudanese persons from childhood to
      young adulthood.
AB  - No current age- and gender-related normative data exist for the dimensions of
      facial structures in Northern Sudanese subjects. In the current study information
      about normal sex- and age-related linear distances is provided. The three
      dimensional coordinates of 14 landmarks on the facial soft tissues were obtained
      using a hand-held laser scanner in 653 healthy Northern Sudanese subjects (326
      males and 327 females) aged 4-30 years. From the landmarks, 13 linear distances
      were calculated, and averaged for age and sex. Comparisons were performed by
      factorial analysis of variance. All analyzed linear soft tissue facial dimensions
      were significantly larger in men than in women (p < 0.01), except mouth width (ch
      ch), upper facial height (n-sn), mandibular body length (pg-go) and width (go
      go). All measurements underwent significant modifications as a function of age (p
      < 0.01), with significant age * sex interactions (p < 0.01) for all linear
      dimensions except lower face height (sn-pg). Overall, when compared to literature
      data for African and Caucasoid subjects, several differences were found, pointing
      to the necessity of ethnic-specific data. Data collected in the present
      investigation could serve as a database for the quantitative description of human
      facial morphology during normal growth and development. 

PMID- 24290255
TI  - The ossified pterygoalar ligament: an anatomical study with pathological and
      surgical implications.
AB  - Mandibular nerve entrapment has great significance, as it may be responsible for
      the appearance of several neurological pathologies, such as chewing disorders,
      taste loss, facial or tongue paraesthesia and neuralgia. The ossified pterygoalar
      (Pta) bar is the result of calcification and/or ossification of the ligament
      extending from the pterygospinous process of the lateral pterygoid lamina to the
      infratemporal surface of the sphenoid bone. The ossified bar may act as the cause
      for this entrapment. One hundred and forty-five Greek adult dry skulls were
      examined for the existence of a complete or incomplete Pta bar and a relative
      foramen. The Pta bar appeared in 31.7% of the skulls, in total, in 4.1%
      completely and in 27.6% incompletely ossified. The mean sagittal and transverse
      diameters of Pta foramen were 3.21 +/- 1.70 and 4.79 +/- 1.39 mm, respectively.
      There was no statistical significant difference between the presence of Pta bar
      and the side or gender. Apart from the neurological interest, this study
      highlights the importance of the existence of Pta bar in neurosurgery,
      anaesthesiology, oral and maxillofacial surgery. The passage of the needle
      through the foramen ovale for the injection of anaesthetics, as a treatment for
      trigeminal neuralgia may not be achieved due to this anatomical obstacle. In this
      case, intra- or postoperative radiologic investigation may be helpful. 

PMID- 24290256
TI  - Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission
      tomography in the assessment of pleural abnormalities in cancer patients: a
      systematic review and a meta-analysis.
AB  - OBJECTIVE: To systematically review and meta-analyze published data about the
      diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron
      emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment
      of pleural abnormalities in cancer patients. METHODS: A comprehensive literature
      search of studies published through June 2013 regarding the role of (18)F-FDG-PET
      and PET/CT in evaluating pleural abnormalities in cancer patients was performed.
      All retrieved studies were reviewed and qualitatively analyzed. Pooled
      sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-)
      and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based
      analysis were calculated. The area under the summary ROC curve (AUC) was
      calculated to measure the accuracy of these methods in the assessment of pleural
      abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung
      cancer only were carried out. RESULTS: Eight studies comprising 360 cancer
      patients (323 with lung cancer) were included. The meta-analysis of these
      selected studies provided the following results: sensitivity 86% [95% confidence
      interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8
      4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No
      significant improvement considering PET/CT studies only and patients with lung
      cancer was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be useful
      diagnostic imaging methods in the assessment of pleural abnormalities in cancer
      patients, nevertheless possible sources of false-negative and false-positive
      results should be kept in mind. The literature focusing on the use of (18)F-FDG
      PET and PET/CT in this setting remains still limited and prospective studies are
      needed.

PMID- 24290257
TI  - The overlooked literary path to modern electrophysiology: philosophical
      dialogues, novels, and travel books.
AB  - The early history of neurophysiology has two important roots. The earlier of the
      two involves various ideas about invisible animal spirits traversing the nerves.
      The other, which emerged during the eighteenth century, is based on the idea that
      the elusive spirits are electrical-that animal electricity really does exist. The
      latter idea stemmed in part from what was being discovered about three types of
      electric fishes and their shocks prior to Galvani's broader claim in 1791 for
      animal electricity. This contribution focuses on how the shocks of each of these
      fishes had been described by three writers outside the fields of physiology and
      medicine: Plato, the well-known Greek philosopher, who actually provided the
      first good description of the powers of torpedo rays; Aphra Behn, a leading
      English Restoration playwright and novelist, who introduced many English speakers
      to the creature that would become best known as the "electric eel"; and Michel
      Adanson, a French botanist, who seemed to be the first to compare albeit the
      electric catfish's shocks to those from a known source of electricity, a Leyden
      jar. All three authors were famous in their day, and all played important roles
      in the history of biological electricity by making others aware of one of
      Nature's wonders, fishes that could "torpify," even without direct contact.

PMID- 24290258
TI  - Oscar Wilde and the brain cell.
AB  - This chapter considers Oscar Wilde's interest in the brain cell as an aesthetic
      object. Offering an account of Wilde's career that analyzes his early interest in
      physiology and philosophy, this chapter argues that Wilde's uniquely aesthetic
      take on the brain suggests that he rejects an account of the self as autonomous
      or self-determining. For many late Victorians brain science threatened both the
      freedom of human action and the legitimacy of beauty because it had the potential
      to invalidate conscious experience. But writers whose work Wilde knew, like John
      Ruskin, W. K. Clifford, and John Tyndall, avoided the despair of materialism by
      using aesthetic terms in their own discussions of life's invisible materials.
      Wilde's art collaborates with the contemporary sciences. His depictions of the
      cell direct the senses to a new field of being that emphasizes the molecular life
      all humans have in common, in which individual responsibility and activity matter
      less than the necessity of beauty.

PMID- 24290259
TI  - Forgetting the madeleine: Proust and the neurosciences.
AB  - Marcel Proust's famous madeleine experience, in which a man recalls his past
      through intense concentration after he tastes a cake dipped in tea, has been
      dubbed the "Proust Phenomenon" by researchers in the neurosciences. The passage
      in Proust's novel, however, has been systematically misread in the scientific
      literature due to the complexity and the ambiguity built into the text. A review
      of work by neuroscientists, popular science writers, and literature scholars
      suggests that the most productive interdisciplinary research occurs not where two
      disciplines converge (the madeleine as olfactory memory cue), but rather where
      they diverge (phenomenal description over quantitative analysis). This chapter
      argues that researchers in neuroscience and neuroaesthetics should forget the
      madeleine in Proust to investigate not only the other cognitive insights offered
      by Proust's vast novel, In Search of Lost Time, but also the ways in which
      Proust's novel seeks to bridge the distance between autobiographical experience
      and critical analysis.

PMID- 24290260
TI  - Optograms and criminology: science, news reporting, and fanciful novels.
AB  - A persistent nineteenth-century urban legend was the notion that photograph-like
      images of the last-seen object or person would be preserved in the eyes of the
      dead. This popular notion followed technological developments (the daguerreotype
      and ophthalmoscope) that antedated by decades a basic understanding of retinal
      physiology. From 1876 to 1877, Boll described photochemical bleaching of the
      retina and produced a crude retinal image that remained briefly visible after
      death in an experimental animal. From 1877 to 1881, Kuhne elaborated the
      processes involved in photochemical transduction, and created more complex
      retinal images, or "optograms," that were visible after the death of experimental
      animals under special laboratory circumstances. In 1880, Kuhne reported the first
      human "optogram" when he examined the eyes following the state execution of a
      convicted murderer. Although the work of these physiologists increased public
      interest in "optography" as a potential tool in forensic investigations, Kuhne
      and his student, Ayres, concluded after an extensive series of investigations
      that optography would never be useful for this purpose. Nevertheless, because of
      the prior tantalizing results, optography became a frequent consideration in
      speculative news reports of sensational unsolved murders, and as a plot device in
      works of fiction, some quite fantastical. Fictional portrayals included works by
      Rudyard Kipling and Jules Verne. Despite denouncement of optography for forensic
      investigations by Kuhne, and by numerous physicians, the general public and mass
      media continued to press for examination of the retinae of murder victims well
      into the twentieth century, particularly in high-profile unsolved cases.

PMID- 24290261
TI  - Phrenology and physiognomy in Victorian literature.
AB  - Phrenology evolved from the work of Franz Joseph Gall (1758-1828) and Johann
      Gaspar Spurzheim (1776-1832), becoming a fixture in Victorian culture, arts and
      letters as well as medicine. Writers such as Thomas Love Peacock (1785-1866) and
      Thomas Hood (1799-1845) initially satirized phrenology, as did playwright and
      composer William S. Gilbert (1836-1911). On the other hand, novelists such as
      Charlotte Bronte (1816-1855), Charles Dickens (1812-1870), George Eliot (1819
      1880), and the poet and essayist Ralph Waldo Emerson (1803-1882) not only
      accepted the principles of this brain-based personality theory but exploited it
      in their characters. The popularity of phrenology in the Victorian period should
      in part be attributed to the popularity of physiognomy which, thanks in large
      part to Johann Christian Lavater (1741-1801), has been thoroughly embedded in
      Western culture since the end of the eighteenth century.

PMID- 24290262
TI  - Neurological and psychological constructs in Sheridan Le Fanu's In a Glass
      Darkly.
AB  - Excepting "Green Tea" and "Carmilla," Sheridan Le Fanu's fiction is generally
      neglected by modern-day readers, yet his work reveals much information about the
      conduct of life in nineteenth century Ireland and England. Le Fanu's works should
      be appreciated for the insights he provides into the psychology of his
      characters; his fiction was written prior to what historians of psychology date
      as the formal establishment of the discipline in 1879, which occurred after his
      death. His fiction also illustrates the emerging medical specialty of neurology,
      although Le Fanu's later writings are more illustrative of his interest in the
      mystical works of Emanuel Swedenborg. His characters frequently suffer from
      "brain fevers" and other maladies that were the subject of intense debate in
      England, continental Europe, and America. His male characters in particular
      suffer from guilty consciences, and suicide is a frequent fate. Each of these
      aspects of Le Fanu's fiction can be found in the 1872 collection In a Glass
      Darkly, which purports to contain five case histories of the German metaphysical
      physician Doctor Martin Hesselius. In this chapter, each of the stories in the
      collection will be described and analyzed for Hesselius' use of psychological,
      neurological, or mystical explanations for the events occurring within the story.
      Hesselius' descriptions of psychological constructs are rather advanced for a
      physician discussing mental disorders in the nineteenth century. His theories
      within this collection of stories with respect to neurology and neuroscience, on
      the other hand, are much more representative of the eighteenth century, something
      that would be natural given that the stories contained in the collection were
      purported to have occurred in the latter decades of the eighteenth or early
      decades of the nineteenth century.

PMID- 24290263
TI  - Lord Byron's physician: John William Polidori on somnambulism.
AB  - John William Polidori (1795-1821) was the Edinburgh-trained physician hired by
      Lord Byron to accompany him to Switzerland, where he participated in the story
      telling event proposed by Byron that led, with Polidori's help, to Mary Shelley's
      Frankenstein. Although those interested in English literature might also remember
      Polidori as the author of The Vampyre, one of the first extended works of fiction
      about vampires, his earlier interest in somnambulism and trance states is only
      beginning to be appreciated. Even more than students of Romantic literature,
      historians of science and medicine seem little aware of what Polidori had written
      about oneirodynia, a synonym for somnambulism, and how his thoughts from 1815
      about such activities reflected the changing medical zeitgeist at this time. This
      chapter examines Polidori's medical thesis in a neuroscience context and compares
      what he wrote to the writings of several other physicians who were fascinated by
      nocturnal wanderings, their causes, their manifestations, and their possible
      treatments.

PMID- 24290264
TI  - Return of the living dead: Re-reading Pierre Flourens' contributions to
      neurophysiology and literature.
AB  - Historians of neurophysiology remember Marie Jean Pierre Flourens (1794-1867) for
      his experimental approach to nineteenth-century debates on cortical localization
      and, in particular, for his successful attacks on Frantz Joseph Gall's (1758
      1828) phrenology (Gall and Spurzheim, 1810-19). Whereas Gall and his colleague,
      Johann Gaspar Spurzheim (1776-1832), posited correlations between features of the
      skull and brain development and claimed to have localized character traits,
      competencies and temperaments in specific cortical regions, Flourens advocated
      cerebral equipotentiality and provided empirical as well as philosophical grounds
      for his theories. Flourens has also been recognized for his contributions to the
      understanding of the cerebellum's role in the coordination of movement, the
      localization of a respiratory center in the medulla oblongata, the relationship
      between the semicircular canals and balance, the role of the periosteum in bone
      growth and regeneration, and finally, the anesthetic properties of chloroform.
      Less known to historians of neuroscience is the fact that Pierre Flourens was not
      only a neurophysiologist and Secretaire Perpetuel of the French Academie des
      Sciences, he was also a member of the Academie Francaise, France's most
      prestigious literary academy. Examining Flourens' contributions as a writer and,
      at the same time, a prime target for criticism and caricature from journalists,
      yields a particularly interesting example of the problematic relations between
      different genres of science writing and their respective publics in mid
      nineteenth-century France.

PMID- 24290265
TI  - Peter Mark Roget: physician, scientist, systematist; his thesaurus and his impact
      on 19th-century neuroscience.
AB  - Peter Mark Roget (1779-1869) is best known for his Thesaurus, a project completed
      late in his long life. He trained as a physician, practiced medicine, and was
      interested in many branches of science. Much of his life was dedicated to the
      systematization of knowledge and identifying relationships. Although not an
      experimentalist in the modern sense of the word, he contributed to "neuroscience"
      in journal and encyclopaedia articles, as well as in books and lectures. He wrote
      extensively on comparative physiology, sensory systems, phrenology, optics, and
      various disorders affecting the nervous system. He viewed his two-volume
      Bridgewater Treatise of 1834 as his most significant achievement, turning to
      physiology and comparative anatomy to argue that God's existence can be seen in
      how living forms and their components are designed. Roget was active in many
      scholarly organizations, most notably the Royal Society of London, where he
      served for more than two decades as its secretary before "retiring" to pursue his
      Thesaurus.

PMID- 24290266
TI  - Bram Stoker's brother, the brain surgeon.
AB  - This essay examines the life and work of Sir William Thornley Stoker, 1st Baronet
      (1845-1912), the eldest brother of Bram Stoker (1847-1912), the author of Dracula
      (1897). Sir William or "Thornley," as he was commonly known, was one of Ireland's
      leading physicians. He performed some of the first brain surgeries in Ireland
      using Sir David Ferrier's maps of the cerebral cortex. From 1879 into the
      twentieth century, Thornley served as inspector for Ireland under the 1876
      Cruelty to Animals Act. In this role, Thornley was responsible for granting
      licenses to researchers who performed experiments on live animals. Due to his
      reservations about animal experimentation, Thornley eventually became an advocate
      for the antivivisection cause, testifying at the second Royal Commission on
      Vivisection (1906-1912). Thornley also influenced Irish literature, albeit
      indirectly. Bram Stoker's composition notes for Dracula show that he consulted
      his older brother about the medical scenes in his novel. Thornley's knowledge of
      cerebral localization and his animal rights advocacy both surface in Dracula.

PMID- 24290267
TI  - Gustave Flaubert, Charles Dickens, and Isaac Pulvermacher's "magic band".
AB  - Around 1850, Isaac L. Pulvermacher (1815-1884) joined the ranks of so-called
      "galvanists" who had, for nearly a century, been touting the shocks and sparks of
      electricity as a miracle cure for all ills, including neurological complaints
      such as palsy and hemiplegia. The famed authors, Gustave Flaubert (1821-1880), in
      France, and Charles Dickens (1812-1870), in England, although contemporaries,
      apparently never met or corresponded. But during their lives, they both became
      aware of Pulvermacher and his patented Hydro-Electric Chains, claimed to impart
      vigor and cure nearly every complaint. Pulvermacher's chains made a cameo
      appearance in Madame Bovary (1857), Flaubert's controversial (and most
      successful) novel. Among Dickens's last letters (1870) was an order for I. L.
      Pulvermacher and Company's "magic band." Since the Victorian age, electrical and
      magnetic cures, for better or worse, continue to be products of both the medical
      profession and quackery.

PMID- 24290268
TI  - Alexander Forbes, Walter Cannon, and science-based literature.
AB  - The Harvard physiologists Alexander Forbes (1882-1965) and Walter Bradford Cannon
      (1871-1945) had an enormous impact on the physiology and neuroscience of the
      twentieth century. In addition to their voluminous scientific output, they also
      used literature to reflect on the nature of science itself and its social
      significance. Forbes wrote a novel, The Radio Gunner, a literary memoir, Quest
      for a Northern Air Route, and several short stories. Cannon, in addition to
      several books of popular science, wrote a literary memoir in the last year of his
      life, The Way of an Investigator. The following will provide a brief overview of
      the life and work of Forbes and Cannon. It will then discuss the way that Forbes
      used literature to express his views about the changing role of communications
      technology in the military, and his evolving view of the nervous system itself as
      a kind of information-processing device. It will go on to discuss the way that
      Cannon used literature to articulate the horrors he witnessed on the battlefield,
      as well as to contribute to the philosophy of science, and in particular, to the
      logic of scientific discovery. Finally, it will consider the historical and
      philosophical value of deeper investigation of the literary productions of
      scientists.

PMID- 24290269
TI  - Neurology, poetry and the first world war of 1914-1918.
AB  - The First World War of 1914-1918 produced a wealth of disability and death and
      much has been written of this catastrophe for mankind. Prose is prolific and much
      poetry has been written too, some of it discussed here; it consists of works by
      healthcare workers and also about the effects of the war upon those who fought
      and those who were left behind. Some of the work is by neurologists and some
      deals with the neurological disorders of those who fought.

PMID- 24290270
TI  - Epilepsy in Dostoevsky.
AB  - Fyodor M. Dostoevsky (Moscow, 1821-Saint Petersburg, 1881) suffered epilepsy
      throughout his whole literary career. The aim here is to understand his condition
      in light of his novels, correspondence, and his contemporaries' accounts as well
      as through the eyes of later generations of neurologists. From Murin (The
      landlady, 1847) to Smerdyakov (The brothers Karamazov, 1880), Dostoevsky
      portrayed up to six characters with epilepsy in his literature. The first
      symptoms of the disease presented in early adulthood, but he was only diagnosed
      with epilepsy a decade later. In 1863 he went abroad seeking expert advice from
      the famous neurologists Romberg and Trousseau. Dostoevsky made an intelligent use
      of epilepsy in his literature (of his experiential auras or dreamy states
      particularly) and through it found a way to freedom from perpetual military
      servitude. His case offers an insight into the natural history of epilepsy (a
      cryptogenic localization related one of either fronto-medial or temporal lobe
      origin using contemporary medical terms), thus inspiring later generations of
      writers and neurologists. Furthermore, it illustrates the good use of an ordinary
      neurological disorder by an extraordinary writer who transformed adversity into
      opportunity.

PMID- 24290271
TI  - Mindblindness: metaphor and neuroaesthetics in the works of Silas Weir Mitchell
      and Simon Baron-Cohen.
AB  - Silas Weir Mitchell's novel, When All the Woods are Green (1894), acknowledges
      the medical use of mindblindness (agnosia) but also casts it as a developmental
      disorder, bringing it provocatively close to how current neuropsychologist, Simon
      Baron-Cohen and his followers use the term in relation to autism. This chapter
      traces the mindblindess metaphor in the works of Mitchell and Baron-Cohen to show
      how mindblindness informs the larger paradigms by which they theorize the brain.
      This analysis suggests that Baron-Cohen, and thus much current thinking about
      autism spectrum conditions, is influenced by Victorian-era cultural assumptions
      and neurosexism, a connection that calls for scrutiny of Baron-Cohen's current
      models of the brain and theories of autism. This chapter also demonstrates the
      extent to which Mitchell used fiction and advocated writing as neuroaesthetic
      tools and thus bridged in his work cognitive science and aesthetics--a connection
      that current scholars of neuroaesthetics are now theorizing.

PMID- 24290272
TI  - Literary aesthetics: beauty, the brain, and Mrs. Dalloway.
AB  - Empirical research indicates that beauty is in part a matter of prototype
      approximation. Some research suggests that unanticipated pattern recognition is
      important as well. This essay begins by briefly outlining an account of beauty
      based on these factors. It goes on to consider complications. Minor complications
      include the partial incompatibility of these accounts and the importance of
      differentiating judgments of beauty from aesthetic response. More serious issues
      include the relative neglect of literature in neurologically-based discussions of
      beauty, which tend to focus on music or visual art. There is also a relative
      neglect of emotion, beyond the reward system. Finally, there is the almost
      complete absence of the sublime. After considering these problems broadly, the
      essay turns to Virginia Woolf's Mrs. Dalloway, examining its treatment of beauty
      and sublimity. The aim of this section is not merely to illuminate Woolf's novel
      by reference to neuroscientific research. It is equally, perhaps more fully, to
      expand our neuroscientifically grounded account of aesthetic response by drawing
      on Woolf's novel. In Mrs. Dalloway, there are gestures toward prototypes and
      patterns in beauty. But the key features are clearly emotional. Specifically, the
      emotions at issue in feelings of beauty and sublimity appear to be primarily
      attachment, on the one hand, and a profound sense of isolation, on the other.
      Woolf's novel also points us toward other features of aesthetic experience,
      crucially including the emotion-sharing that is a key function of the production
      and circulation of art.

PMID- 24290273
TI  - Literature, neurology, and neuroscience: historical and literary connections.
      Preface.

PMID- 24290274
TI  - Transfusion and Apheresis Science. Editorial 49.3.

PMID- 24290275
TI  - Host-microbial interactions in patients with chronic rhinosinusitis.
AB  - There has been considerable investigation of host-microbial interactions in
      patients with chronic rhinosinusitis (CRS) in hopes of elucidating mechanisms of
      disease and better treatment. Most attention has been paid to bacterial infection
      and potential underlying defects in innate immunity. Bacterial biofilm is present
      in most patients with CRS undergoing surgical intervention, and its presence is
      associated with more severe disease and worse surgical outcomes. A role for viral
      or fungal infection in patients with CRS is less clear. There is no evidence for
      a primary defect in mucociliary clearance in most patients with CRS. Decreased
      levels of certain antimicrobial proteins, most notably lactoferrin, have been
      found in sinus secretions, whereas levels of other antimicrobial proteins have
      been found to be normal. No primary defects in Toll-like receptors have been
      found in patients with CRS, although a 50% reduced expression of Toll-like
      receptor 9 was reported in patients with recalcitrant nasal polyps. A
      polymorphism in a bitter taste receptor was recently associated with refractory
      CRS and persistent Pseudomonas aeruginosa infection. A downregulation of innate
      immunity by maladaptive TH2 tissue inflammation has also been described in
      patients with recalcitrant nasal polyps, suggesting a link to persistent
      infection. To date, an effective means of restoring host-microbial balance and
      mitigating disease in patients with CRS remains elusive.

PMID- 24290276
TI  - Monitoring childhood asthma: web-based diaries and the asthma control test.
AB  - BACKGROUND: Data from asthma diaries are frequently used as an end point in
      asthma studies; however, data on the validity of Web-based diaries are scarce.
      OBJECTIVES: First, we examined the validity of a Web-based diary in assessing
      asthma control. Second, we determined the cutoff points for well-controlled
      asthma of the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test
      (ACT), and calculated the minimal important difference for both tests. METHODS:
      Children with asthma, ages 4-18 years (n = 228) completed a 4-week Web-based
      diary, C-ACT, ACT, and an asthma-related quality-of-life questionnaire at
      baseline and after 1-year follow-up. RESULTS: The completion rate of the Web
      based diaries was 89%. The diary scores correlated strongly with C-ACT and ACT
      scores (r = -0.73, P < .01; r = -0.64, P < .01, respectively) and the changes in
      diary scores correlated well with changes in C-ACT and ACT scores. The best
      cutoff points for well-controlled asthma were C-ACT >= 22 and ACT >= 23. The
      minimal important differences were 1.9 (95% CI, 1.3-2.5) for ACT and 1.6 (95% CI,
      1.1-2.1) for C-ACT, and -0.7 points/d (95% CI, -1.1 to -0.4) for the Web-based
      diary. CONCLUSIONS: Our Web-based diary was valid for recording asthma symptoms.
      Cutoff points of >=22 (C-ACT) and >=23 (ACT) define well-controlled asthma. We
      recommend a 2 C-ACT and ACT points difference as minimally important.

PMID- 24290278
TI  - Premature immune senescence during HIV-1 vertical infection relates with response
      to influenza vaccination.

PMID- 24290277
TI  - Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary
      inflammation.
AB  - BACKGROUND: The diverse roles of innate immune cells in the pathogenesis of
      asthma remain to be fully defined. Natural killer (NK) cells are innate
      lymphocytes that can regulate adaptive immune responses. NK cells are activated
      in asthma; however, their role in allergic airway inflammation is not fully
      understood. OBJECTIVE: We investigated the importance of NK cells in house dust
      mite (HDM)-triggered allergic pulmonary inflammation. Specifically, we aimed to
      determine the role of the major NK-cell activating receptor NKG2D and NK-cell
      effector functions mediated by granzyme B. METHODS: Allergic airway inflammation
      was induced in the airways of mice by repeated intranasal HDM extract
      administration and responses in wild-type and NKG2D-deficient mice were compared.
      Adoptive transfer studies were used to identify the cells and mechanisms
      involved. RESULTS: Mice that lacked NKG2D were resistant to the induction of
      allergic inflammation and showed little pulmonary eosinophilia, few airway TH2
      cells, and no rise in serum IgE after multiple HDM-allergen exposures. However,
      NKG2D was not required for pulmonary inflammation after a single inoculation of
      allergen. NKG2D-deficient mice showed no alteration in responses to respiratory
      virus infection. Transfer of wild-type NK cells (but not CD3(+) cells) into NKG2D
      deficient mice restored allergic inflammatory responses only if the NK cells
      expressed granzyme B. CONCLUSIONS: These studies established a pivotal role for
      NK-cell NKG2D and granzyme B in the pathogenesis of HDM-induced allergic lung
      disease, and identified novel therapeutic targets for the prevention and
      treatment of asthma.

PMID- 24290279
TI  - The activating protein 1 transcription factor basic leucine zipper transcription
      factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune
      responses in the setting of allergic asthma.
AB  - BACKGROUND: Mice without the basic leucine zipper transcription factor, ATF-like
      (BATF) gene (Batf(-/-)) lack TH17 and follicular helper T cells, which
      demonstrates that Batf is a transcription factor important for T- and B-cell
      differentiation. OBJECTIVE: In this study we examined whether BATF expression
      would influence allergic asthma. METHODS: In a cohort of preschool control
      children and children with asthma, we analyzed BATF mRNA expression using real
      time PCR in PBMCs. In a murine model of allergic asthma, we analyzed differences
      in this allergic disease between wild-type, Batf transgenic, and Batf(-/-) mice.
      RESULTS: In the absence of corticosteroid treatment, children with recurrent
      asthma have a significant increase in BATF mRNA expression in their PBMCs. Batf(
      /-) mice display a significant reduction in the pathophysiologic responses seen
      in asthmatic wild-type littermates. Moreover, we discovered a decrease in IL-3
      production and IL-3-dependent mast cell development in Batf(-/-) mice. By
      contrast, IFN-gamma was induced in lung CD4(+) and CD8(+) T cells. Intranasal
      delivery of anti-IFN-gamma antibodies induced airway hyperresponsiveness and
      inflammation in wild-type but not in Batf(-/-) mice. Transgenic overexpression of
      Batf under the control of the CD2 promoter/enhancer augmented lung inflammation
      and IgE levels in the setting of experimental asthma. CONCLUSION: BATF is
      increased in non-steroid-treated asthmatic children. Targeting BATF expression
      resulted in amelioration of the pathophysiologic responses seen in children with
      allergic asthma, and BATF has emerged as a novel target for antiasthma
      interventions.

PMID- 24290280
TI  - Unsuspected mild emphysema in nonsmoking patients with chronic asthma with
      persistent airway obstruction.

PMID- 24290282
TI  - Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response
      followed by regulatory T-cell generation.
AB  - BACKGROUND: Sublingual administration of Phleum pratense allergen immunotherapy
      (SLIT) tablets is a clinically efficient treatment for grass pollen-induced
      rhinoconjunctivitis. This immunotherapy downregulates TH2 immune responses,
      induces tolerogenic pathways, and increases regulatory T cells. However,
      associated immune response markers of allergen desensitization remain undefined.
      OBJECTIVE: We sought to characterize the kinetics of individual changes in the
      immunologic response to grass tablet SLIT. METHODS: We evaluated the systemic
      effects of SLIT in a longitudinal analysis of humoral and cellular immune
      parameters in peripheral blood samples. RESULTS: Grass tablet SLIT administration
      induced a 2-phase systemic humoral and cellular response. The TH2 response was
      initially exacerbated and detected as increased allergen-specific IgE (sIgE) and
      IgG4 (sIgG4) levels and an increase in IL-4-producing cells, followed by
      downregulation of the TH2 response with a shift toward a TH1 cytokine profile. T
      cells with a regulatory phenotype were also elicited. Statistical correlations
      between immunologic measurements for each patient throughout therapy indicated
      that TH2 response downregulation and reduction of the immediate SLIT-induced IgE
      response were associated with increased allergen-specific IgG4 synthesis early in
      therapy. TH2 response downregulation by month 4 correlated with increased
      frequency of CD4(+) T cells with a regulatory phenotype by 12 months. CONCLUSION:
      Changes in sIgE levels after therapy were linked to a specific IgG4 response, and
      production of blocking antibodies correlated with TH2 response downregulation.
      Reduced IL-4(+) cell frequency was linked to an increase in the frequency of
      CD4(+) T cells with a regulatory phenotype. Changes in sIgE levels and reduced IL
      4 and blocking antibody levels could thus be used as indicators of a patient's
      immune response to therapy.

PMID- 24290281
TI  - Asthma across the ages: knowledge gaps in childhood asthma.
AB  - The Eunice Kennedy Shriver National Institute of Child Health and Human
      Development convened an Asthma Group in response to the Best Pharmaceuticals for
      Children Act. The overall goal of the Best Pharmaceuticals for Children Act
      Program is to improve pediatric therapeutics through preclinical and clinical
      drug trials that lead to drug-labeling changes. Although significant advances
      have been made in the understanding and management of asthma in adults with
      appropriately labeled medications, less information is available on the
      management of asthma in children. Indeed, many medications are inadequately
      labeled for use in children. In general, the younger the child, the less
      information there is available to guide clinicians. Because asthma often begins
      in early childhood, it is incumbent on us to continue to address the primary
      questions raised in this review and carefully evaluate the medications used to
      manage asthma in children. Meanwhile, continued efforts should be made in
      defining effective strategies that reduce the risk of exacerbations. If the areas
      of defined need are addressed in the coming years, namely prevention of
      exacerbations and progression of disease, as well as primary intervention, we
      will see continuing reduction in asthma mortality and morbidity along with
      improved quality of life for children with asthma.

PMID- 24290283
TI  - Pattern recognition receptor-mediated cytokine response in infants across 4
      continents.
AB  - BACKGROUND: Susceptibility to infection as well as response to vaccination varies
      among populations. To date, the underlying mechanisms responsible for these
      clinical observations have not been fully delineated. Because innate immunity
      instructs adaptive immunity, we hypothesized that differences between populations
      in innate immune responses may represent a mechanistic link to variation in
      susceptibility to infection or response to vaccination. OBJECTIVE: Determine
      whether differences in innate immune responses exist among infants from different
      continents of the world. METHODS: We determined the innate cytokine response
      following pattern recognition receptor (PRR) stimulation of whole blood from 2
      year-old infants across 4 continents (Africa, North America, South America, and
      Europe). RESULTS: We found that despite the many possible genetic and
      environmental exposure differences in infants across 4 continents, innate
      cytokine responses were similar for infants from North America, South America,
      and Europe. However, cells from South African infants secreted significantly
      lower levels of cytokines than did cells from infants from the 3 other sites, and
      did so following stimulation of extracellular and endosomal but not cytosolic
      PRRs. CONCLUSIONS: Substantial differences in innate cytokine responses to PRR
      stimulation exist among different populations of infants that could not have been
      predicted. Delineating the underlying mechanism(s) for these differences will not
      only aid in improving vaccine-mediated protection but possibly also provide clues
      for the susceptibility to infection in different regions of the world.

PMID- 24290284
TI  - A systematic analysis of recombination activity and genotype-phenotype
      correlation in human recombination-activating gene 1 deficiency.
AB  - BACKGROUND: The recombination-activating gene (RAG) 1/2 proteins play a critical
      role in the development of T and B cells by initiating the VDJ recombination
      process that leads to generation of a broad T-cell receptor (TCR) and B-cell
      receptor repertoire. Pathogenic mutations in the RAG1/2 genes result in various
      forms of primary immunodeficiency, ranging from T(-)B(-) severe combined immune
      deficiency to delayed-onset disease with granuloma formation, autoimmunity, or
      both. It is not clear what contributes to such heterogeneity of phenotypes.
      OBJECTIVE: We sought to investigate the molecular basis for phenotypic diversity
      presented in patients with various RAG1 mutations. METHODS: We have developed a
      flow cytometry-based assay that allows analysis of RAG recombination activity
      based on green fluorescent protein expression and have assessed the induction of
      the Ighc locus rearrangements in mouse Rag1(-/-) pro-B cells reconstituted with
      wild-type or mutant human RAG1 (hRAG1) using deep sequencing technology. RESULTS:
      Here we demonstrate correlation between defective recombination activity of hRAG1
      mutant proteins and severity of the clinical and immunologic phenotype and
      provide insights on the molecular mechanisms accounting for such phenotypic
      diversity. CONCLUSIONS: Using a sensitive assay to measure the RAG1 activity
      level of 79 mutations in a physiologic setting, we demonstrate correlation
      between recombination activity of RAG1 mutants and the severity of clinical
      presentation and show that RAG1 mutants can induce specific abnormalities of the
      VDJ recombination process.

PMID- 24290285
TI  - Associations between serum folate and vitamin D levels and incident mouse
      sensitization in adults.
AB  - BACKGROUND: Although both folic acid intake and vitamin D levels are hypothesized
      to be contributors to the increased incidence of allergic diseases, prospective
      studies of these relationships have not been done in adults. OBJECTIVES: We
      sought to determine whether serum folate or vitamin D levels are associated with
      incident mouse sensitization among new workers at a mouse facility. METHODS:
      Subjects started employment at the Jackson Laboratory between June 2004 and July
      2007. Skin testing to mouse and other allergens and collection of questionnaire
      data were performed at baseline and every 6 months. Serum folate and vitamin D
      levels were assessed on baseline samples stored at -80 degrees C. Folate was
      categorized into tertiles (2.5-10.5, 10.5-16.2, and 16.2-78.4 ng/mL,
      respectively). Vitamin D was categorized as less than 20 ng/mL, 20 to 29 ng/mL,
      or 30 ng/mL or greater. This was a nested case-control study in which 5 control
      subjects were matched to each case on baseline atopy and type of employment.
      Multivariate analyses controlled for age, sex, education, smoking, season,
      personal mouse exposure, and serum folate and vitamin D levels. RESULTS: Thirty
      five cases and 47 control subjects were included. The odds of incident mouse
      sensitization were higher in the intermediate and highest tertiles of serum
      folate compared with the lowest tertile of serum folate (odds ratio of 10.5 [95%
      CI, 1.8-61.5; P = .009] and odds ratio of 5.6 [95% CI, 1.8-31.3; P = .049],
      respectively, in the multivariate model). Serum vitamin D levels were not
      associated with incident mouse sensitization. CONCLUSIONS: These findings support
      a role for higher serum folate levels in increased risk of incident allergic
      disease, even during adulthood.

PMID- 24290286
TI  - Effectiveness of voriconazole in the treatment of Aspergillus fumigatus
      associated asthma (EVITA3 study).
AB  - BACKGROUND: IgE sensitization to Aspergillus fumigatus and a positive sputum
      fungal culture result are common in patients with refractory asthma. It is not
      clear whether these patients would benefit from antifungal treatment. OBJECTIVES:
      We sought to determine whether a 3-month course of voriconazole improved asthma
      related outcomes in patients with asthma who are IgE sensitized to A fumigatus.
      METHODS: Asthmatic patients who were IgE sensitized to A fumigatus with a history
      of at least 2 severe exacerbations in the previous 12 months were treated for 3
      months with 200 mg of voriconazole twice daily, followed by observation for 9
      months, in a double-blind, placebo-controlled, randomized design. Primary
      outcomes were improvement in quality of life at the end of the treatment period
      and a reduction in the number of severe exacerbations over the 12 months of the
      study. RESULTS: Sixty-five patients were randomized. Fifty-nine patients started
      treatment (32 receiving voriconazole and 27 receiving placebo) and were included
      in an intention-to-treat analysis. Fifty-six patients took the full 3 months of
      medication. Between the voriconazole and placebo groups, there were no
      significant differences in the number of severe exacerbations (1.16 vs 1.41 per
      patient per year, respectively; mean difference, 0.25; 95% CI, 0.19-0.31),
      quality of life (change in Asthma Quality of Life Questionnaire score, 0.68 vs
      0.88; mean difference between groups, 0.2; 95% CI, -0.05 to -0.11), or any of our
      secondary outcome measures. CONCLUSION: We were unable to show a beneficial
      effect of 3 months of treatment with voriconazole in patients with moderate-to
      severe asthma who were IgE sensitized to A fumigatus on either the rate of severe
      exacerbations, quality of life, or other markers of asthma control.

PMID- 24290287
TI  - Identification of Hymenoptera venom-allergic patients with negative specific IgE
      to venom extract by using recombinant allergens.

PMID- 24290288
TI  - Asthma phenotyping: TH2-high, TH2-low, and beyond.

PMID- 24290289
TI  - Nasal mucus proteomic changes reflect altered immune responses and epithelial
      permeability in patients with allergic rhinitis.
AB  - BACKGROUND: Nasal mucus is the first-line defense barrier against (aero-)
      allergens. However, its proteome and function have not been clearly investigated.
      OBJECTIVE: The role of nasal mucus in the pathophysiology of allergic rhinitis
      was investigated by analyzing its proteome in patients with allergic rhinitis (n
      = 29) and healthy control subjects (n = 29). METHODS: Nasal mucus was collected
      with a suction device, tryptically digested, and analyzed by using liquid
      chromatography-tandem mass spectrometry. Proteins were identified by searching
      the SwissProt database and annotated by collecting gene ontology data from
      databases and existing literature. Gene enrichment analysis was performed by
      using Cytoscape/BINGO software tools. Proteins were quantified with spectral
      counting, and selected proteins were confirmed by means of Western blotting.
      RESULTS: In total, 267 proteins were identified, with 20 (7.5%) found exclusively
      in patients with allergic rhinitis and 25 (9.5%) found exclusively in healthy
      control subjects. Five proteins were found to be significantly upregulated in
      patients with allergic rhinitis (apolipoprotein A-2 [APOA2], 9.7-fold; alpha2
      macroglobulin [A2M], 4.5-fold; apolipoprotein A-1 [APOA1], 3.2-fold; alpha1
      antitrypsin [SERPINA1], 2.5-fold; and complement C3 [C3], 2.3-fold) and 5 were
      found to be downregulated (antileukoproteinase [SLPI], 0.6-fold; WAP 4-disulfide
      core domain protein [WFDC2], 0.5-fold; haptoglobin [HP], 0.7-fold; IgJ chain
      [IGJ], 0.7-fold; and Ig hc V-III region BRO, 0.8-fold) compared with levels seen
      in healthy control subjects. CONCLUSION: The allergic rhinitis mucus proteome
      shows an enhanced immune response in which apolipoproteins might play an
      important role. Furthermore, an imbalance between cysteine proteases and
      antiproteases could be seen, which negatively affects epithelial integrity on
      exposure to pollen protease activity. This reflects the important role of mucus
      as the first-line defense barrier against allergens.

PMID- 24290291
TI  - Enrichment of the rare CD4+ gammadelta T-cell subset in patients with atypical
      CD3delta deficiency.

PMID- 24290290
TI  - Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children.
AB  - BACKGROUND: Whether adiposity indicators other than body mass index (BMI) should
      be used in studies of childhood asthma is largely unknown. The role of atopy in
      "obese asthma" is also unclear. OBJECTIVES: To examine the relationship among
      adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess
      whether atopy mediates the obesity-asthma association. METHODS: In a study of
      Puerto Rican children with (n = 351) and without (n = 327) asthma, we measured
      BMI, percent of body fat, waist circumference, and waist-to-hip ratio. The
      outcomes studied included asthma, lung function, measures of atopy, and, among
      cases, indicators of asthma severity or control. We performed mediation analysis
      to assess the contribution of atopy to the relationship between adiposity and
      asthma. RESULTS: BMI, percent of body fat, and waist circumference were
      associated with increased odds of asthma. Among cases, all 3 measures were
      generally associated with lung function, asthma severity/control, and atopy;
      however, there were differences depending on the adiposity indicator analyzed.
      Atopy considerably mediated the adiposity-asthma association in this population:
      allergic rhinitis accounted for 22% to 53% of the association with asthma, and
      sensitization to cockroach mediated 13% to 20% of the association with forced
      vital capacity and 29% to 42% of the association with emergency department visits
      for asthma. CONCLUSIONS: Adiposity indicators are associated with asthma, asthma
      severity/control, and atopy in Puerto Rican children. Atopy significantly
      mediates the effect of adiposity on asthma outcomes. Longitudinal studies are
      needed to further investigate the causal role, if any, of adiposity distribution
      and atopy on "obese asthma" in childhood.

PMID- 24290293
TI  - The development of prospective memory in preschool children using naturalistic
      tasks.
AB  - The development of prospective memory (PM) in 3-, 4-, and 5-year-old children
      (N=123) was assessed in two experiments using several naturalistic game-like
      tasks that varied in the explicitness of the cues for retrieval that they
      provided. The goals of the study were to evaluate age differences in PM (a) with
      the effects of retrospective memory (RM) factored out and (b) as a function of
      increasing retrieval cue specificity. Results from Experiment 1 showed that there
      were age differences in PM on a simulated Shopping Trip task that favored older
      children after age differences attributable to RM were identified in a
      hierarchical regression. PM and RM components followed the same developmental
      trajectory. Because the Shopping Trip task provided a visual cue for retrieval, a
      second naturalistic PM task that was incidental to the Shopping Trip task (i.e.,
      to ask for stickers at the end of the shopping trip) was included but provided no
      explicit cue other than the end of Shopping Trip task itself. A binary logistic
      regression showed that age did not predict children who succeeded and those who
      did not succeed. Because the end of the Shopping Trip task might have cued PM,
      two new tasks without any explicit cues for retrieval were examined in Experiment
      2. Logistic regressions revealed that age predicted PM success on both tasks.
      With additional cues following failure to retrieve the PM intention, nearly all
      children succeeded, but the number of cues needed increased with age. The joint
      and separate contributions of PM and RM to successful task performance are
      discussed. 

PMID- 24290292
TI  - Establishing diagnostic criteria for severe combined immunodeficiency disease
      (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment
      Consortium experience.
AB  - BACKGROUND: The approach to the diagnosis of severe combined immunodeficiency
      disease (SCID) and related disorders varies among institutions and countries.
      OBJECTIVES: The Primary Immune Deficiency Treatment Consortium attempted to
      develop a uniform set of criteria for diagnosing SCID and related disorders and
      has evaluated the results as part of a retrospective study of SCID in North
      America. METHODS: Clinical records from 2000 through 2009 at 27 centers in North
      America were collected on 332 children treated with hematopoietic stem cell
      transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and
      related disorders. Eligibility for inclusion in the study and classification into
      disease groups were established by using set criteria and applied by an expert
      review group. RESULTS: Two hundred eighty-five (86%) of the patients were
      determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible
      patients, 84% were classified as having typical SCID; 13% were classified as
      having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history
      of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID
      phenotype was accepted for eligibility. Reasons for noneligibility were failure
      to demonstrate either impaired lymphocyte proliferation or maternal T-cell
      engraftment. Overall (n = 332) rates of testing were as follows: proliferation to
      PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in
      62%). CONCLUSION: Lack of complete laboratory evaluation of patients before HCT
      presents a significant barrier to definitive diagnosis of SCID and related
      disorders and prevented inclusion of subjects in our observational HCT study.
      This lesson is critical for patient care, as well as the design of future
      prospective treatment studies for such children because a well-defined and
      consistent study population is important for precision in outcomes analysis.

PMID- 24290294
TI  - Enhanced dechlorination of carbon tetrachloride by Geobacter sulfurreducens in
      the presence of naturally occurring quinones and ferrihydrite.
AB  - The effect of naturally occurring quinones including lawsone (LQ), ubiquinone
      (UQ), juglone (JQ), and 1,4-naphthoquinone (NQ) on the biotransformation of
      carbon tetrachloride (CT) in the presence of Geobacter sulfurreducens and
      ferrihydrite was investigated. AQDS was used as the model compound for
      comparison. The reductive dissolution of ferrihydrite by G. sulfurreducens was
      enhanced by AQDS, NQ, and LQ. However, addition of UQ and JQ had little
      enhancement effect on Fe(II) production. The bioreduction efficiency and rate of
      ferrihydrite was highly dependent on the natural property and concentration of
      quinone compounds and the addition of low concentrations of LQ and NQ
      significantly accelerated the biotransformation rate of CT. The pseudo-first
      order rate constants for CT dechlorination (kobsCT) in AQDS-, LQ- and NQ-amended
      batches were 5.4-5.8, 4.6-7.4 and 2.4-5.8 times, respectively, higher than those
      in the absence of quinone. A good relationship between kobsCT for CT
      dechlorination and bioreduction ratio of ferrihydrite was observed, indicating
      the important role of biogenic Fe(II) in dechlorination of CT under iron-reducing
      conditions. Spectroscopic analysis showed that AQDS and NQ could be reduced to
      semiquinones and hydroquinones, while only hydroquinones were generated in LQ
      amended batches. 

PMID- 24290295
TI  - Joint toxicity of heavy metals and chlorobenzenes to pyriformis Tetrahymena.
AB  - Chlorobenzens and heavy metals are frequently detected in the environment, but
      few studies have assessed the joint toxicity of organic and inorganic
      contaminants. The joint toxicity of heavy metals and chlorobenzenes was evaluated
      in the present study. Growth metabolism of the joint toxicity was studied by
      microcalorimetry at 28 degrees C, the growth constant (k) and inhibitory ratio
      (I) were calculated. Toxic unit (TU) and additional index (AI) were introduced to
      determine the outcome in combined tests, and the coexistence of Cu, Cd, Cr(III)
      and p-chlorobenzene was antagonism, and the effect of Cu, Cd, Cr(III) and o
      chlorobenzene, Cu and 1,2,4-trichlorobenzene were synergism. In addition, micro
      situation of the cell membrane surface of pyriformis Tetrahymena was observed by
      SEM. The cells suffered serious damage after sufficient acting time. ATR-FTIR
      spectra revealed that amide groups and PO2(-) of the phospholipid phospho
      diester, both in the hydrophobic end exposed to the outer layer, were the easiest
      to be damaged. 

PMID- 24290296
TI  - Nonylphenol effects on the HPA axis of the bioindicator vertebrate, Podarcis
      sicula lizard.
AB  - Nonylphenol (NP) is an endocrine disruptor widely distributed in the environment.
      It accumulates in the lipids of living organisms and enters the human food chain.
      The main source of human exposure is expected to be food, drinking water and
      foodstuff contaminated through leaching from packaging or pesticide formulation
      applications. NP acts as an estrogenic compound and it is able to mimic the
      action of estradiol 17beta (E2) by binding to the estrogen receptor (ER). The aim
      of the present study was to investigate the NP effects on the hypothalamic
      pituitary-adrenal gland (HPA) axis of the bioindicator Podarcis sicula lizard. A
      time-dependent stimulation of the HPA axis and variations of both catecholamine
      plasma levels were showed. Moreover, NP effects on adrenal gland morphology were
      evaluated by light and transmission electron microscopy. Clear morphological
      signs of adrenal gland stimulation such as an increase of steroidogenic cord
      diameter and vascularization, a strong escalation of adrenaline cell number and a
      decrease of noradrenaline cells were observed. The notably elevated levels of
      adrenal hormones suggested a permanent turning on of hypothalamic corticotropin
      releasing factor (CRF) secretion together with a lack of the negative feedback of
      HPA axis, perturbing systemic responses of the organism. Our data may help to
      predict the biological alterations induced by NP and to extend its impact upon
      adrenal function. 

PMID- 24290297
TI  - Photodegradation of gallic acid under UV irradiation: insights regarding the pH
      effect on direct photolysis and the ROS oxidation-sensitized process of DOM.
AB  - In this study, the degradation of gallic acid (GA), a model compound for
      dissolved organic matter (DOM) in controlled UV/N2, UV/air, UV/Fe(3+)/N2, and
      UV/Fe(3+)/air systems was investigated to elucidate the contribution of direct
      photolysis and reactive oxygen species (ROS) oxidation to GA degradation at
      various pH values. In general, the order of the degradation rate of GA in these
      four systems was as follows: UV/Fe(3+)/air>UV/air>UV/Fe(3+)/N2~UV/N2. In the
      UV/N2 system, GA underwent slow direct photolysis, the rate of which decreased
      with decreasing pH. In the UV/Fe(3+)/air system, the most rapid GA degradation
      was achieved at pH 5. ROS are mainly derived from two sources. The first source
      is attributed to the role of DO and the other is attributed to the interaction of
      Fe(3+) and DO. The contribution of ROS to GA oxidation is much greater (>71%)
      than that of direct photolysis (<29%) at each pH value and is most obvious at pH
      5. H2O2 formation was detected during GA degradation in the UV/air and
      UV/Fe(3+)/air systems. Using ROS scavengers, it was found that oxidation by OH
      was the main mechanism of GA degradation in the UV/Fe(3+)/air system. Based on
      the experimental results, a mechanism for GA degradation and ROS formation
      involving the effect of pH was proposed. This study furthers our understanding of
      changes in DOM degradation mechanisms due to global acidification. 

PMID- 24290298
TI  - Start-up period investigation of pilot-scale submerged membrane electro
      bioreactor (SMEBR) treating raw municipal wastewater.
AB  - Submerged membrane electro-bioreactor (SMEBR) is a new hybrid technology for
      wastewater treatment employing electrical field and microfiltration in a nutrient
      removing activated sludge process. A pilot SMEBR system was located at the
      wastewater treatment plant in the City of l'Assomption (Quebec, Canada) with the
      objective of investigating the start-up period performance under variable organic
      loadings and environmental conditions with respect to effluent quality, membrane
      fouling, and sludge properties. The pilot SMEBR facility was fed with the raw de
      gritted municipal wastewater. At steady state operation, the removal efficiencies
      of ammonia (as NH3(+)-N), phosphorus (as PO4(3-)-P), and COD were 99%, 99%, and
      92%, respectively. No substantial increase in the monitored transmembrane
      pressure as 0.02kPad(-1) was reported. The time necessary to filter 100mL of the
      sludge sample has decreased by 78% after treatment whilst the sludge volume index
      averaged 119mLg(-1). Energy requirements were in the range of 1.1-1.6kWhm(-3) of
      wastewater. It was concluded that the SMEBR is a very competitive technology when
      compared to conventional membrane systems as it can enhance treatment performance
      to an appreciable extent, remove phosphorus and reduce fouling. 

PMID- 24290299
TI  - Synthesis of hierarchical Mg-doped Fe3O4 micro/nano materials for the
      decomposition of hexachlorobenzene.
AB  - An ethylene-glycol (EG) mediated self-assembly process was firstly developed to
      synthesize micrometer-sized nanostructured Mg-doped Fe3O4 composite oxides to
      decompose hexachlorobenzene (HCB) at 300 degrees C. The synthesized samples were
      characterized by scanning electron microscopy, transmission electron microscopy,
      X-ray diffraction, energy dispersive X-ray spectroscopy and inductively coupled
      plasma optical emission spectrometer. The morphology and composition of the
      composite oxide precursor were regulated by the molar ratio of the magnesium
      acetate and ferric nitrate as the reactants. Calcination of the precursor
      particles, prepared with different molar ratio of the metal salts, under a
      reducing nitrogen atmosphere, generated three kinds of Mg doped Fe3O4 composite
      oxide micro/nano materials. Their reactivity toward HCB decomposition was likely
      influenced by the material morphology and content of Mg dopants. Ball-like
      MgFe2O4-Fe3O4 composite oxide micro/nano material showed superior HCB
      dechlorination efficiencies when compared with pure Fe3O4 micro/nano material,
      prepared under similar experimental conditions, thus highlighting the benefits of
      doping Mg into Fe3O4 matrices. 

PMID- 24290300
TI  - Brominated flame retardants and Dechloranes in European and American eels from
      glass to silver life stages.
AB  - The populations of American (Anguilla rostrata) and European eels (Anguilla
      anguilla) have been declining rapidly in the last decades. Organic contaminants
      are suspected to be one of the possible causes for the decline; however, so far
      there have been few investigations of the uptake of specific compounds by
      different life cycle stages (e.g. freshwater or marine stage) and how the
      contamination patterns develop throughout the eel's life cycle. In the present
      study we measured concentrations of polybrominated diphenylethers (PBDEs),
      alternate brominated flame retardants (alternate BFRs) and Dechloranes (Decs) in
      different life stages of European and American eels to compare the contamination
      patterns and their development throughout the eel's life cycle. In general,
      concentrations of flame retardants (FRs) were similar to or higher in American
      than in European eels, and a greater number of FRs were detected. PBDE congeners
      that are characteristic of the Penta-PBDE formulation were the most abundant FRs
      in all adult eels as well as American glass eels. In European glass eels the
      alternate BFR 2,3-dibromopropyl-2,4,6-tribromophenylether (DPTE) and Dechlorane
      Plus were the dominating FRs, with average concentrations of 1.1+/-0.31 ng g(-1)
      ww and up to 0.32 ng g(-1) ww respectively. Of the PBDEs BDE-183 was the most
      abundant congener in European glass eels. Low concentrations (less than 10% of
      the total contamination) of Tetra and Penta-PBDEs in juvenile European eels
      indicated that bans of technical Penta-PBDE in the European Union are effective.
      Enrichment of PBDEs was observed over the life stages of both European and
      American eels. However, a greater relative contribution of PBDEs to the sum FR
      contamination in American eels indicated an on-going exposure to these
      substances. High contributions of alternate BFRs in juvenile eels indicated an
      increased use of these substances in recent years. Concentrations seemed to be
      driven primarily by location, rather than life stage or age.

PMID- 24290301
TI  - The solubility of liquid and solid compounds in dry octan-1-ol.
AB  - Using literature data on solubilities, equations have been constructed for the
      correlation of solubilities of liquids and solids in dry octanol, as log Soct
      (M). The best equation statistically uses Abraham descriptors together with the
      compound melting point. For 282 compounds the equation standard deviation is no
      more than 0.47 log units. If the melting point term is omitted the standard
      deviation rises to 0.63 log units. It is suggested that if Abraham descriptors
      are available, these equations represent the most satisfactory equations for the
      correlation and estimation of solubilities in dry octanol. If these descriptors
      are not available, then the simple equation of Yalkowsky can be used, although
      for 223 compounds the equation standard deviation rises to 0.71 log units. 

PMID- 24290302
TI  - Contamination trends of trace metals and coupling with algal productivity in
      sediment cores in Pearl River Delta, South China.
AB  - Several sediment cores from the Pearl River Delta were collected to investigate
      the relationship of trace metal contamination with algae-derived organic matter
      in the last 50 years. Trace metals were analyzed with ICP-MS, and algal organic
      matter (AOM) was measured with Rock-Eval pyrolysis. It was found that Cu, Zn, Ag,
      Cd, and As were elevated in the last three decades from three reservoirs, while
      all of the target metals showed no significant enrichment in estuarine sediment
      cores. Cu, Cr, Co, Cd, Zn, Ag, Ni, As, and Mn normalized to Ti were strongly
      associated with AOM in the sediments of eutrophic reservoirs, suggesting that AOM
      played an important role in controlling the accumulation of trace metals.
      Principal component analysis (PCA) and enrichment factor (EF) were also used to
      assess the enrichment of trace metals. The above result indicated that the
      sedimentary process of As, Cd, Cu, Zn, Ni, Cr, Co, Ag, and Mn was significantly
      affected or/and controlled by primary productivity in eutrophic, non-point
      polluted reservoirs.

PMID- 24290303
TI  - Mercury in dumped blast furnace sludge.
AB  - Blast furnace sludge (BFS) is a waste generated in the production of pig iron and
      was dumped in sedimentation ponds. Sixty-five samples from seven BFS locations in
      Europe were investigated regarding the toxic element mercury (Hg) for the first
      time. The charge material of the blast furnace operations revealed Hg contents
      from 0.015 to 0.097mgkg(-1). In comparison, the Hg content of BFS varied between
      0.006 and 20.8mgkg(-1) with a median of 1.63mgkg(-1), which indicates enrichment
      with Hg. For one site with a larger sample set (n=31), Hg showed a stronger
      correlation with the total non-calcareous carbon (C) including coke and graphite
      (r=0.695; n=31; p<0.001). It can be assumed that these C-rich compounds are
      hosting phases for Hg. The solubility of Hg was rather low and did not exceed
      0.43% of total Hg. The correlation between the total Hg concentration and total
      amount of NH4NO3-soluble Hg was relatively poor (r=0.496; n=27; p=0.008)
      indicating varying hazard potentials of the different BFS. Finally, BFS is a
      mercury-containing waste and dumped BFS should be regarded as potentially mercury
      contaminated sites. 

PMID- 24290304
TI  - Effects of washing solution and drying condition on reactivity of nano-scale zero
      valent irons (nZVIs) synthesized by borohydride reduction.
AB  - Washing and drying processes are essential when synthesizing nano-scale zero
      valent irons (nZVIs) by borohydride reduction of iron salts in aqueous phase.
      However, effects of these processes on nZVI reactivity have not been investigated
      in detail, although different washing and drying conditions might alter surface
      characteristics of nZVIs and thus vary their reactivity towards reducible
      contaminants. In this study, effects of three washing solutions and drying
      conditions on the reactivity of nZVIs for nitrate were investigated. Washing with
      volatile solvents and drying under anaerobic condition decreased thickness of Fe
      oxide layer on nZVIs and increased content of Fe(2+)-containing oxides in the
      layer, which enhanced nZVI reactivity toward nitrate. Volatile solvent washing
      could minimize the decrease in nZVI reactivity according to changing anaerobic
      drying condition to aerobic. Findings from this study suggest that application of
      washing with volatile solvents and drying under aerobic condition should be
      recommended as effective processes to obtain nZVIs with maximum reactivity at
      reasonable costs and efforts. 

PMID- 24290305
TI  - Novel airway findings in a patient with 1p36 deletion syndrome.
AB  - 1p36 deletion syndrome comprises a phenotypic presentation that includes central
      nervous system, cardiac, and craniofacial anomalies. There has been no report of
      associated airway anomalies with this syndrome. We present here a case report and
      literature review. Prenatally, amniocentesis for chromosomal analysis was
      performed on our patient, with results consistent with 1p36 deletion syndrome.
      Respiratory distress and unsuccessful attempts at intubation prompted transfer to
      Children's Hospital of Colorado. Microlaryngoscopy was subsequently performed,
      revealing a persistent buccopharyngeal membrane and unidentifiable larynx.
      Emergent tracheostomy was then performed to secure the airway. Airway anomalies
      may be associated with 1p36 deletion syndrome. 

PMID- 24290306
TI  - Synchronous occurrence of nasopharyngeal carcinoma and Hodgkin lymphoma.
AB  - Latent Epstein-Barr virus infection is associated with several lymphoid and
      epithelial malignancies. This is the first reported case of a patient presenting
      with synchronous nasopharyngeal carcinoma and Hodgkin lymphoma associated with
      Epstein-Barr virus. A 17-year-old previously healthy African-American male
      presented with anterior mediastinal mass and a nasopharyngeal mass. Histology
      from biopsy of both lesions revealed evidence of Epstein-Barr virus. The patient
      successfully completed sequential therapies with chemo radiation with no evidence
      of active disease. Simultaneous occurrence of the two malignancies is undoubtedly
      a rare event, and their coexistence raises the question of a common etiologic
      factor. 

PMID- 24290307
TI  - Clinical value of fine needle aspiration cytology in pediatric cervical
      lymphadenopathy patients under 12-years-of-age.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness and accuracy
      of fine needle aspiration cytology (FNAC) in the diagnosis of pediatric cervical
      lymphadenopathy in patients under 12-years-of-age. METHODS: A retrospective chart
      review was performed to evaluate patients under 12-years-of-age with cervical
      lymphadenopathy who underwent lymph node excision biopsy from January 2007 to
      June 2013. The results of FNAC were compared them with the corresponding
      histopathological diagnosis. RESULTS: Eighteen of the 27 patients had undergone
      FNAC before performing excision biopsy, which diagnosed benign diseases in 15
      patients and malignant diseases in three patients. All 18 patients underwent
      excision biopsy. FNAC had a diagnostic sensitivity of 100%, positive-predictive
      value of 93.3%, and accuracy of 94.5% for diagnosing pediatric cervical
      lymphadenopathy. CONCLUSIONS: FNAC is a useful and accurate adjunct for the
      evaluation of pediatric cervical lymphadenopathy. FNAC should be part of the
      initial evaluation of pediatric patients with cervical lymphadenopathy before
      determining the treatment plan.

PMID- 24290308
TI  - Outcomes of implants placed with three different flapless surgical procedures: a
      systematic review.
AB  - The aim of this systematic review was to evaluate the outcomes of flapless
      surgery for implants placed using either free-hand or guided (with or without 3D
      navigation) surgical methods. Literature searches were conducted to collect
      information on survival rate, marginal bone loss, and complications of implants
      placed with such surgeries. Twenty-three clinical studies with a minimum of 1
      year follow-up time were finally selected and reviewed. Free-hand flapless
      surgery demonstrated survival rates between 98.3% and 100% and mean marginal bone
      loss between 0.09 and 1.40 mm at 1-4 years after implant insertion. Flapless
      guided surgery without 3D navigation showed survival rates between 91% and 100%
      and mean marginal bone loss of 0.89 mm after an observation period of 2-10 years.
      The survival rates and mean marginal bone loss for implants placed with 3D guided
      flapless surgery were 89-100% and 0.55-2.6mm, respectively, at 1-5 years after
      implant insertion. In 17 studies, surgical and technical complications such as
      bone perforation, fracture of the surgical guide, and fracture of the provisional
      prosthesis were reported. However, none of the identified methods has
      demonstrated advantages over the others. Further studies are needed to confirm
      the predictability and effectiveness of 3D navigation techniques.

PMID- 24290309
TI  - [Theoretical investigation of the saturation correction for ionization chambers
      irradiated with pulsed beams of arbitrary pulse length].
AB  - In ionization chambers, not all released charge is collected due to the
      recombination of charge carriers. This effect is taken into account by the
      saturation correction factor kS. A physical description of the correction factor
      has been established for pulsed radiation. However, it is only accurate when the
      pulse length is short compared with the collection time of the ionization
      chamber. In this paper we develop a description of the saturation correction for
      radiation pulses of arbitrary length. For this, a system of partial differential
      equations is solved iteratively. The numerical solutions are verified
      experimentally for a Roos ionization chamber (PTW TM34001) exposed to a pulsed
      electron beam. The results of this iterative procedure describe the experimental
      data well. The calculations are also possible for beam structures which are
      experimentally hard to get and thereby contribute to a better understanding and
      correct description of the saturation correction at arbitrary pulse length. Among
      other things the pulse length dependent distributions of the charge carriers in
      the ionization chamber is calculated, inclusive of the transition to the
      conditions prevailing in the case of continuous irradiation. Furthermore is shown
      that the formula for kS established by Hochhauser and Balk is applicable even at
      arbitrary pulse length, if pulse duration dependent effective values are used for
      the parameters a and p. These effective values have been determined for the Roos
      chamber at pulse lengths up to 300 MUs.

PMID- 24290310
TI  - Operant alcohol self-administration in dependent rats: focus on the vapor model.
AB  - Alcoholism (alcohol dependence) is characterized by a compulsion to seek and
      ingest alcohol (ethanol), loss of control over intake, and the emergence of a
      negative emotional state during withdrawal. Animal models are critical in
      promoting our knowledge of the neurobiological mechanisms underlying alcohol
      dependence. Here, we review the studies involving operant alcohol self
      administration in rat models of alcohol dependence and withdrawal with the focus
      on the alcohol vapor model. In 1996, the first articles were published reporting
      that rats made dependent on alcohol by exposure to alcohol vapors displayed
      increased operant alcohol self-administration during acute withdrawal compared
      with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has
      been repeatedly demonstrated that this model reliably produces physical and
      motivational symptoms of alcohol dependence. The functional roles of various
      systems implicated in stress and reward, including opioids, dopamine,
      corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY),
      gamma-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been
      investigated in the context of alcohol dependence. The combination of models of
      alcohol withdrawal and dependence with operant self-administration constitutes an
      excellent tool to investigate the neurobiology of alcoholism. In fact, this work
      has helped lay the groundwork for several ongoing clinical trials for alcohol
      dependence. Advantages and limitations of this model are discussed, with an
      emphasis on what future directions of great importance could be. 

PMID- 24290312
TI  - Characterization and prediction of rate-dependent flexibility in lumbar spine
      biomechanics at room and body temperature.
AB  - BACKGROUND CONTEXT: The soft tissues of the spine exhibit sensitivity to strain
      rate and temperature, yet current knowledge of spine biomechanics is derived from
      cadaveric testing conducted at room temperature at very slow, quasi-static rates.
      PURPOSE: The primary objective of this study was to characterize the change in
      segmental flexibility of cadaveric lumbar spine segments with respect to multiple
      loading rates within the range of physiologic motion by using specimens at body
      or room temperature. The secondary objective was to develop a predictive model of
      spine flexibility across the voluntary range of loading rates. STUDY DESIGN: This
      in vitro study examines rate- and temperature-dependent viscoelasticity of the
      human lumbar cadaveric spine. METHODS: Repeated flexibility tests were performed
      on 21 lumbar function spinal units (FSUs) in flexion-extension with the use of 11
      distinct voluntary loading rates at body or room temperature. Furthermore, six
      lumbar FSUs were loaded in axial rotation, flexion-extension, and lateral bending
      at both body and room temperature via a stepwise, quasi-static loading protocol.
      All FSUs were also loaded using a control loading test with a continuous-speed
      loading-rate of 1-deg/sec. The viscoelastic torque-rotation response for each
      spinal segment was recorded. A predictive model was developed to accurately
      estimate spine segment flexibility at any voluntary loading rate based on
      measured flexibility at a single loading rate. RESULTS: Stepwise loading
      exhibited the greatest segmental range of motion (ROM) in all loading directions.
      As loading rate increased, segmental ROM decreased, whereas segmental stiffness
      and hysteresis both increased; however, the neutral zone remained constant.
      Continuous-speed tests showed that segmental stiffness and hysteresis are
      dependent variables to ROM at voluntary loading rates in flexion-extension. To
      predict the torque-rotation response at different loading rates, the model
      requires knowledge of the segmental flexibility at a single rate and specified
      temperature, and a scaling parameter. A Bland-Altman analysis showed high
      coefficients of determination for the predictive model. CONCLUSIONS: The present
      work demonstrates significant changes in spine segment flexibility as a result of
      loading rate and testing temperature. Loading rate effects can be accounted for
      using the predictive model, which accurately estimated ROM, neutral zone,
      stiffness, and hysteresis within the range of voluntary motion.

PMID- 24290311
TI  - Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol
      drinking (HAD) rats: modeling adolescent and adult binge-like drinking.
AB  - Binge alcohol drinking continues to be a public health concern among today's
      youth and young adults. Moreover, an early onset of alcohol use, which usually
      takes the form of binge drinking, is associated with a greater risk for
      developing alcohol use disorders. Given this, it is important to examine this
      behavior in rat models of alcohol abuse and dependence. Toward that end, the
      objective of this article is to review findings on binge-like drinking by
      selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of
      rats. As reviewed elsewhere in this special issue, the P line meets all, and the
      HAD line meets most, of the proposed criteria for an animal model of alcoholism.
      One model of binge drinking is scheduled ethanol access during the dark cycle,
      which has been used by our laboratory for over 20 years. Our laboratory has also
      adopted a protocol involving the concurrent presentation of multiple ethanol
      concentrations. When this protocol is combined with limited access, ethanol
      intake is maximized yielding blood ethanol levels (BELs) in excess, sometimes
      greatly in excess, of 80 mg%. By extending these procedures to include multiple
      scheduled ethanol access sessions during the dark cycle for 5 consecutive
      days/week, P and HAD rats consume in 3 or 4 h as much as, if not more than, the
      amount usually consumed in a 24 h period. Under certain conditions, using the
      multiple scheduled access procedure, BELs exceeding 200 mg% can be achieved on a
      daily basis. An overview of findings from studies with other selectively bred,
      inbred, and outbred rats places these findings in the context of the existing
      literature. Overall, the findings support the use of P and HAD rats as animal
      models to study binge-like alcohol drinking and reveal that scheduled access
      procedures will significantly increase ethanol intake by other rat lines and
      strains as well. 

PMID- 24290313
TI  - Minimally invasive transforaminal lumbar interbody fusion: one surgeon's learning
      curve.
AB  - BACKGROUND CONTEXT: The published literature has not characterized the surgeon's
      learning curve with the technically demanding technique of a minimally invasive
      transforaminal lumbar interbody fusion (MIS TLIF). PURPOSE: To characterize based
      on intra- and perioperative parameters, the learning curve for one spine surgeon
      during his initial phases of performing an MIS TLIF. STUDY DESIGN/SETTING:
      Retrospective analysis of a single institution and single surgeon experience with
      the unilateral MIS TLIF technique between July 2008 and April 2011. PATIENT
      SAMPLE: Sixty-five consecutive patients, with at least 1 year of follow-up, who
      underwent a unilateral, single-level, index MIS TLIF for the diagnosis of
      degenerative disk disease or lumbar spinal stenosis with grade I or II
      spondylolisthesis were analyzed based on data obtained from the medical records
      and postoperative imaging (computed tomography). OUTCOME MEASURES: Postoperative
      radiographic assessment of fusion at 1 year via computed tomography. Surgical
      parameters of surgical time (skin-skin, minutes), anesthesia time (induction
      extubation, minutes), estimated blood loss (mL), intravenous fluids during
      surgery (mL), intraoperative complications (durotomy), and postoperative
      complications (pseudarthrosis, implant failure, malpositioned implants, graft
      related complications) were also assessed. METHODS: The senior author's first 100
      consecutive MIS TLIFs were evaluated initially. Patients undergoing revision or
      multilevel surgery were excluded leaving a total of 65 consecutive primary MIS
      TLIFs. The first 33 patients were compared with the second 32 patients in terms
      of radiographic arthrodesis rates, surgical parameters, and intra-/postoperative
      complications. A two-tailed Student t test was used to assess for differences
      between the two cohorts where a p value of less than or equal to .05 denoting
      statistical significance. Pearson's correlation coefficient was used to determine
      any association between the date of surgery and surgical time. RESULTS: Average
      surgical time, estimated blood loss, intraoperative fluids, and duration of
      anesthesia was significantly longer in the first cohort (p<.05). There were no
      significant differences in intraoperative complications (two durotomies in both
      groups) or length of stay. There was no significant difference in postoperative
      complications at final follow-up based on computed tomography analysis (11 vs. 9,
      p=.649). In the first cohort, these complications included two cases of
      radiographic pseudarthrosis: one case of graft migration and one case of medial
      pedicle wall violation necessitating two revision surgeries. There were two cases
      of pseudarthrosis and one case of an early surgical site infection identified in
      the second group requiring three revision surgeries. Last, four cases of
      neuroforaminal bone growth were demonstrated, two in each cohort. Pearson's
      correlation coefficient demonstrated a negative correlation between the date of
      surgery and surgical time (r=-0.44; p<.001) estimated blood loss (r=-0.49;
      p<.001), duration of anesthesia (r=-0.41; p=.001), and intravenous fluids (r=
      0.42; p=.001). CONCLUSIONS: The MIS TLIF is a technically difficult procedure to
      the practicing spine surgeon with regard to intra- and perioperative parameters
      of surgical time, estimated blood loss, intravenous fluid, and duration of
      anesthesia. Operative time and proficiency improved with understanding the
      minimally invasive technique. Further studies are warranted to delineate the
      methods to minimize the complications associated with the learning curve.

PMID- 24290314
TI  - An advisory program for first- and second-year medical students: the Weill
      Cornell experience.
AB  - PURPOSE: First-year students negotiate new professional culture with a certain
      amount of excitement and anxiety. There are different approaches for offering
      guidance. In this study, the authors present Weill Cornell Medical College's
      experience with an advising program for first- and second-year students. METHODS:
      Fifty faculty advisors were each assigned 1-3 first-year students who they would
      follow for 2 years. The responsibilities were outlined to both faculty and
      students. The program was evaluated using an anonymous questionnaire. RESULTS:
      For the two classes surveyed (2011 and 2012), most students met their advisors
      once. For both classes, the most frequently discussed issues were general
      adjustment to medical school, academic life, and the professional life of the
      advisor. Summer research and career opportunities were also discussed. Most
      students were satisfied with the advising program. Satisfaction increased with an
      increase in visits. Most students who did not meet their advisors established an
      advisor relationship on their own. CONCLUSIONS: An advising program was
      established at Weill Cornell Medical College that satisfied most of the students.
      It is important to evaluate its format regularly, from both student and advisor
      perspectives, in order to ensure its continued success.

PMID- 24290317
TI  - [Peroral endoscopic full and partial-thickness myotomy. A viability study in an
      animal model].
AB  - BACKGROUND: Peroral endoscopic myotomy has recently been developed and performed
      on patients with good results. AIMS: To evaluate the technical feasibility of
      peroral endoscopic full-thickness and partial thickness myotomy in a porcine
      model. MATERIAL AND METHODS: Eighteen criollo pigs were randomly assigned to 2
      groups: group A (partial-thickness myotomy) and group B (full-thickness myotomy).
      The mucosal defect proximal to the myotomy site was left open. On the seventh
      postoperative day the pig was euthanized and follow-up surgical exploration was
      performed. The duration of each procedure, postoperative progression of the
      animal, complications, and anatomopathologic findings were registered. RESULTS:
      The procedure was viable in all the pigs. The mean surgery duration was 81+/
      35.3min (group A 51.11+/-11.12, group B 111+/-22.61; P<.05). The main
      complication during myotomy was subcutaneous emphysema (16%). The histopathologic
      study of the group A surgical specimens reported complete circular myotomy in all
      cases, and complete circular and longitudinal myotomy was reported in 100% of the
      group B sample. CONCLUSIONS: The endoscopic myotomy technique is feasible.
      Endoscopic partial-thickness myotomy was associated with shorter surgery duration
      and better results during the intraoperative period and the 7-day follow-up.

PMID- 24290318
TI  - [Frequency of visualization of celiac ganglia by endoscopic ultrasound and its
      potential in assessing neural invasion in patients with pancreatic lesions].
AB  - BACKGROUND: Celiac ganglia (CG) can be seen by endoscopic ultrasound; they play
      an important role in pain management and are a potential site for extrapancreatic
      tumor neural invasion. AIMS: To evaluate the frequency of CG visualization during
      endoscopic ultrasound examination and to evaluate the feasibility of this
      technique to identify extrapancreatic tumor neural invasion in patients with
      pancreatic lesions. METHODS: We retrospectively reviewed all endoscopic
      ultrasound studies performed between November 2007 and June 2010. Images of the
      celiac region were presented to an endosonographer, who reported the presence or
      absence of CG. RESULTS: We included 31 cases. CG were identified in 14 (45%)
      cases. Average size was 10mm (range 4-25mm) by+/-1mm (range 1-7mm). In 2 cases,
      fine needle aspiration biopsy was performed and reported nerve cell bodies; in
      one case malignant cells were seen. CONCLUSIONS: CG were identified in 45% of the
      cases. Fine needle aspiration biopsy can detect unanticipated extrapancreatic
      tumor neural invasion in pancreatic malignancies.

PMID- 24290319
TI  - [Gut microbiota in health and disease].
AB  - Gut microbiota is the community of live microorganisms residing in the digestive
      tract. There are many groups of researchers worldwide that are working at
      deciphering the collective genome of the human microbiota. Modern techniques for
      studying the microbiota have made us aware of an important number of
      nonculturable bacteria and of the relation between the microorganisms that live
      inside us and our homeostasis. The microbiota is essential for correct body
      growth, the development of immunity, and nutrition. Certain epidemics affecting
      humanity such as asthma and obesity may possibly be explained, at least
      partially, by alterations in the microbiota. Dysbiosis has been associated with a
      series of gastrointestinal disorders that include non-alcoholic fatty liver
      disease, celiac disease, and irritable bowel syndrome. The present article deals
      with the nomenclature, modern study techniques, and functions of gut microbiota,
      and its relation to health and disease. 

PMID- 24290320
TI  - [The prevalence of irritable bowel symptoms in a population of shopping mall
      visitors in Santiago de Chile].
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal
      disorder characterized by abdominal pain or discomfort that is associated with
      altered bowel habit. Both its prevalence and clinical characteristics vary
      throughout Latin America. A percentage of patients does not seek medical
      attention, therefore a reliable prevalence figure can only be established by
      interviewing non-selected populations. AIMS: To study the prevalence and clinical
      characteristics of IBS symptoms in non-selected subjects in Santiago, Chile.
      METHODS: A total of 437 shopping mall visitors above the age of 15 years (246
      women) participated in the study by answering the Rome II validated questionnaire
      for IBS. The demographic and socioeconomic backgrounds, comorbidities, and a
      family history of IBS were registered. RESULTS: A total of 64.1% subjects
      reported having gastrointestinal symptoms and 28.6% had symptoms suggestive of
      IBS. When the subjects with IBS symptoms were compared with the asymptomatic
      individuals, a predominance of women (65.6 vs. 42.9, P<.001) and a greater
      cholecystectomy frequency (33.6 vs. 12.9% P<.05) were observed in the former. The
      age of symptom onset was 30.4 years. An equal percentage of subjects (42.4%)
      presented with diarrhea and constipation and 15.2% presented with alternating
      IBS. Participants with a higher educational level reported a lower percentage of
      IBS (P<.05). A family history of the disease was present in 40% of the subjects
      with IBS, compared with 14.9% in the asymptomatic individuals (P<.05). Only 39.2%
      of the subjects had seen a physician for their symptoms and the treatment and
      tests ordered were inappropriate. CONCLUSION: The prevalence of IBS symptoms in
      the population studied is one of the highest described. Therefore, health teams
      should have the necessary knowledge and skill required for its management.

PMID- 24290321
TI  - [Solitary fibrous tumor confined to the small bowel (ileum) mesentery].

PMID- 24290322
TI  - The central role of conventional 12-lead ECG for the assessment of microvascular
      obstruction after percutaneous myocardial revascularization.
AB  - Guidelines report that the optimal treatment for ST-elevation myocardial
      infarction (STEMI) is a primary percutaneous coronary intervention (PPCI) when
      performed timely by trained operators. Yet, the reopening of the infarct-related
      artery (IRA) is not always followed by myocardial reperfusion. This phenomenon is
      most commonly called "no-reflow", is caused by microvascular obstruction (MVO)
      and is associated to a worse outcome. Electrocardiogram (ECG) is crucial for the
      diagnosis of STEMI, but is also useful for the assessment of MVO. In this review
      we summarize ECG-derived parameters associated to MVO and their prognostic
      relevance. 

PMID- 24290323
TI  - Nurses' perceptions of accessing a Medical Emergency Team: a qualitative study.
AB  - BACKGROUND: Medical Emergency Teams (METs) have been developed and implemented
      with the aim of improving recognition of and response to deteriorating patients.
      Yet, METs are often not activated or used effectively by nursing staff. The
      reasons for this are not fully understood. OBJECTIVES: The aim of this study was
      to explore nurses' experiences and perceptions of using and activating a MET, in
      order to understand the facilitators and barriers to nurse's use of the MET.
      DESIGN, SETTING AND PARTICIPANTS: An interpretive qualitative approach was
      adopted to explore nurses' experiences and perceptions of using and activating
      the MET. This study was set in a large public teaching hospital in Southeast
      Queensland, Australia. Fifteen registered ward nurses who had cared for patients
      who had deteriorated on the ward, and as a result of this deterioration were
      admitted to the Intensive Care Unit (ICU) as an unplanned admission, were
      interviewed about their experiences and perceptions of using a MET. METHODS: In
      depth, semi-structured interviews were conducted with ward nurses who had cared
      for a patient who had deteriorated. Interviews were recorded and transcribed
      verbatim. The interviews were analysed thematically. FINDINGS: Four themes
      relating to the participants' experiences and perceptions of using a MET emerged
      from the data. These themes were: (1) sensing clinical deterioration; (2)
      resisting and hesitating; (3) pushing the button; and (4) support and leadership.
      CONCLUSION: This work identifies why nurses do not activate METs appropriately.
      This delay in MET activation potentially exposes the deteriorating patient to
      suboptimal care and increases the risk of adverse events.

PMID- 24290324
TI  - HTA and innovation of value: getting to know you.

PMID- 24290325
TI  - Approaches to identifying, measuring, and aggregating elements of value.
AB  - BACKGROUND: Two general alternative approaches, cost-effectiveness analysis and
      the therapeutic added value approach, link the pricing and approval of drugs to
      value. Value as assessed by payers is a function of: benefit less cost,
      willingness to pay for benefit, and how they handle uncertainty. METHODS: This
      study uses international examples to explore the elements of value that can be
      included in the assessment of health technologies, approaches to scoring the
      elements of value and how they can be combined to make a decision. RESULTS: A
      range of value elements, measures, and approaches to aggregation are identified
      across different HTA systems. We show that seemingly arbitrary differences in
      measurement and aggregation can lead to significantly different outcomes, and
      argue that the choice of values, measures, and decision-making processes should
      be informed by the societal values that underpin a health system. CONCLUSIONS: We
      identify three areas for further research to improve both health system and
      industry R&D decision making: (i) whether more consistency could be achieved
      across health systems on the elements of value that matter; (ii) the relative
      merits of discrete versus continuous measures of value; and (iii) how structured
      decision making (to aggregate the elements of value) could or should become.

PMID- 24290326
TI  - Dynamics of device innovation: implications for assessing value.
AB  - BACKGROUND: In recent years, there has been growing interest in evaluating the
      health and economic impact of medical devices. Payers increasingly rely on cost
      effectiveness analyses in making their coverage decisions, and are adopting value
      based purchasing initiatives. These analytic approaches, however, have been
      shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to
      the medical device context. METHODS: This study focuses on the development and
      evaluation of left ventricular assist devices (LVADs) to highlight the unique
      challenges involved in the design and conduct of device trials compared with
      pharmaceuticals. RESULTS: Devices are moving targets characterized by a much
      higher degree of post-introduction innovation and "learning by using" than
      pharmaceuticals. The cost effectiveness ratio of left ventricular assist devices
      for destination therapy, for example, decreased from around $600,000 per life
      year saved based on results from the pivotal trial to around $100,000 within a
      relatively short time period. CONCLUSIONS: These dynamics pose fundamental
      challenges to the evaluation enterprise as well as the policy-making world, which
      this paper addresses.

PMID- 24290327
TI  - HTA and value--a commentary.

PMID- 24290328
TI  - HTA and value--a commentary.

PMID- 24290329
TI  - HTA and value--an industry perspective.

PMID- 24290330
TI  - Telemedical versus conventional heart patient monitoring: a survey study with
      German physicians.
AB  - OBJECTIVES: In this study, we explored crucial factors that explain a person's
      attitude toward and his or her assessment of telemedical systems. Special focus
      lies on the link between the perspective of physicians (telemedicine users) and
      technicians (telemedicine designers) to find potential barriers hindering the
      broad application of telemedical systems in hospitals and doctors' offices.
      METHODS: A survey among medical professionals (n = 34), technical professionals
      (n = 39), and a control group (n = 44) was conducted. The collected data were
      assessed in terms of domain knowledge, attitudes toward telemedicine, and
      potential implementation barriers. RESULTS: Participants favored the conventional
      method over telemedical monitoring in regards to privacy, security, and time
      efficiency. In contrast, telemedicine was preferred with reference to efficiency
      of data analysis, long-term care, and emergency adequacy. Significant differences
      between the professional groups were found regarding perceived cost
      effectiveness, patients' compliance, privacy protection, and false alarm
      sensitivity. Medical professionals exhibited the most reluctance toward using
      telemedical treatments. CONCLUSIONS: The perceived drawbacks are attributed to a
      general uncertainty about the reliability of telemedical systems, in combination
      with concerns about personal data privacy, security, and loss of control. The
      reported fear of not being able to correctly use and handle the systems assumes a
      low usability of devices. To acquaint medical professionals with the benefits and
      limitations of telemedical systems, telemonitoring and tele-treatment should be
      included in the education of medical personnel at an early stage.

PMID- 24290332
TI  - Comparative effectiveness of anti-VEGF agents for diabetic macular edema.
AB  - OBJECTIVES: The aim of this study was to evaluate the comparative effectiveness
      of anti-vascular endothelial growth factor therapy in the treatment of diabetic
      macular edema (DME). METHODS: Searches focused on reports concerning treatment of
      DME with aflibercept, bevacizumab, pegaptanib, or ranibizumab published between
      January 2000 and June 30, 2012, with comparisons to laser photocoagulation, sham
      injection, or other control (e.g., triamcinolone). Effectiveness was based on
      best-corrected visual acuity (BCVA), in terms of letters gained. Direct meta
      analyses were conducted on BCVA for each anti-vascular endothelial growth factor
      (VEGF) agent; indirect comparisons also were performed for each anti-VEGF pair.
      RESULTS: A total of fifteen randomized controlled trials (eleven fair- or good
      quality) and eight observational studies were included. No direct comparative
      studies were identified. Improvement in visual acuity versus control was seen
      with all agents (range: 4-9 letters); outcomes were consistent across multiple
      timepoints. Meta-analyses showed no statistically significant and/or consistent
      differences between agents in BCVA changes or the percentage of patients gaining
      more than ten letters. No discernible differences in the potential harms of anti
      VEGFs, including ocular events, MI, stroke, and other cardiovascular events, as
      well as death, were noted between aflibercept, pegaptanib, and ranibizumab. Data
      on harms for bevacizumab were underreported. CONCLUSIONS: All anti-VEGF agents
      are effective in improving visual acuity in comparison to laser photocoagulation.
      Evidence is insufficient to distinguish the performance of any single anti-VEGF
      agent over others. The safety of bevacizumab remains the greatest element of
      uncertainty.

PMID- 24290331
TI  - Is treatment of depression cost-effective in people with diabetes? A systematic
      review of the economic evidence.
AB  - OBJECTIVES: Depression is common in diabetes and linked to a wide range of
      adverse outcomes. UK policy indicates that depression should be treated using
      conventional psychological treatments in a stepped care framework. This review
      aimed to identify current economic evidence of psychological treatments for
      depression among people with diabetes. METHOD: Electronic search strategies
      (conducted in MEDLINE, EMBASE, PsycINFO, CINAHL, NHS EED) combined clinical and
      economic search terms to identify full economic evaluations of the relevant
      interventions. Prespecified screening and inclusion criteria were used.
      Standardized data extraction and critical appraisal were conducted and the
      results summarized qualitatively. RESULTS: Excluding duplicates, 1,516 studies
      for co-morbid depression and diabetes were screened. Four economic evaluations
      were identified. The studies found that the interventions improved health status,
      reduced depression and were cost-effective compared with usual care. The studies
      were all U.S.-based and evaluated collaborative care programs that included
      psychological therapies. Critical appraisal indicated limitations with the study
      designs, analysis and results for all studies. CONCLUSIONS: The review
      highlighted the paucity of evidence in this area. The four studies indicated the
      potential of interventions to reduce depression and be cost-effective compared
      with usual care. Two studies reported costs per QALY gained of USD 267 to USD
      4,317, whilst two studies reported the intervention dominated usual care, with
      net savings of USD 440 to USD 612 and net gains in patient free days or QALYs.

PMID- 24290333
TI  - Cost-utility of self-managed computer therapy for people with aphasia.
AB  - OBJECTIVES: The aim of this study was to examine the potential cost-effectiveness
      of self-managed computer therapy for people with long-standing aphasia post
      stroke and to estimate the value of further research. METHODS: The incremental
      cost-effectiveness ratio of computer therapy in addition to usual stimulation
      compared with usual stimulation alone was considered in people with long-standing
      aphasia using data from the CACTUS trial. A model-based approach was taken. Where
      possible the input parameters required for the model were obtained from the
      CACTUS trial data, a United Kingdom-based pilot randomized controlled trial that
      recruited thirty-four people with aphasia and randomized them to computer
      treatment or usual care. Cost-effectiveness was described using an incremental
      cost-effectiveness ratio (ICER) together with cost-effectiveness acceptability
      curves. A value of information analysis was undertaken to inform future research
      priorities. RESULTS: The intervention had an ICER of L3,058 compared with usual
      care. The likelihood of the intervention being cost-effective was 75.8 percent at
      a cost-effectiveness threshold of L20,000 per QALY gained. The expected value of
      perfect information was L37 million. CONCLUSIONS: Our results suggest that
      computer therapy for people with long-standing aphasia is likely to represent a
      cost-effective use of resources. However, our analysis is exploratory given the
      small size of the trial it is based upon and therefore our results are uncertain.
      Further research would be of high value, particularly with respect to the quality
      of life gain achieved by people who respond well to therapy.

PMID- 24290334
TI  - Impact of educational interventions on adverse drug events reporting.
AB  - INTRODUCTION: Spontaneous adverse drug events (ADE) reporting is the main source
      of data for assessing the risk/benefit of drugs available in the pharmaceutical
      market. However, its major limitation is underreporting, which hinders and delays
      the signal detection by Pharmacovigilance (PhV). OBJECTIVES: To identify the
      techniques of educational intervention (EI) for promotion of PhV by health
      professionals and to assess their impact. METHODS: A systematic review was
      performed in the PUBMED, PAHO, LILACS and EMBASE databases, from November/2011 to
      January/2012, updated in March/2013. The strategy search included the use of
      health descriptors and a manual search in the references cited by selected
      papers. RESULTS: 101 articles were identified, of which 16 met the inclusion
      criteria. Most of these studies (10) were conducted in European hospitals and
      physicians were the health professionals subjected to most EI (12), these studies
      lasted from one month to two years. EI with multifaceted techniques raised the
      absolute number, the rate of reporting related to adverse drug reactions (ADR),
      technical defects of health technologies, and also promoted an improvement in the
      quality of reports, since there was increased reporting of ADR classified as
      serious, unexpected, related to new drugs and with high degree of causality.
      CONCLUSION: Multifaceted educational interventions for multidisciplinary health
      teams working at all healthcare levels, with sufficient duration to reach all
      professionals who act in the institution, including issues related to medication
      errors and therapeutic ineffectiveness, must be validated, with the aim of
      standardizing the Good Practice of PhV and improve drug safety indicators.

PMID- 24290335
TI  - Health technology reassessment: the art of the possible.
AB  - BACKGROUND: Health technology reassessment (HTR) is "a structured, evidence-based
      assessment of the clinical, social, ethical, and economic effects of a technology
      currently used in the healthcare system, to inform optimal use of that technology
      in comparison to its alternatives." The purpose of this study is to describe the
      key themes in the context of current HTR activities and propose a way forward for
      this newly emerging field. METHODS: Data were gathered from a workshop held as
      part of the 2012 Canadian Agency for Drugs and Technology in Health (CADTH)
      symposium. The workshop consisted of two panel presentations followed by
      discussion; data gathered, including presentations and rich audience discussion
      transcripts, were analyzed for key themes emerging in the field of HTR using
      constant comparative analysis. RESULTS: The language chosen to describe HTR will
      set the tone for engagement. The identification of champions at multiple levels
      and political will are essential. Key lessons from international experience are:
      disinvestment is difficult, focus on clinical areas not specific technologies,
      identify clear goals of the HTR agenda. Six key themes were identified to move
      the HTR agenda forward: emphasize integration over segregation, focus on
      development of HTR methods and processes, processes are context-specific but
      lessons must be shared, build capacity in synergistic interdisciplinary fields,
      develop meaningful stakeholder engagement, strengthen postimplementation
      monitoring and evaluation. CONCLUSIONS: To move this field forward, we must
      continue to build on international experiences with a focus on developing novel
      methodological approaches to generating, incorporating, and implementing evidence
      into policy and practice.

PMID- 24290336
TI  - Mapping of health technology assessment in selected countries.
AB  - OBJECTIVES: The aim of this study was to develop and apply an instrument to map
      the level of health technology assessment (HTA) development at country level in
      selected countries. We examined middle-income countries (Argentina, Brazil,
      India, Indonesia, Malaysia, Mexico, and Russia) and countries well-known for
      their comprehensive HTA programs (Australia, Canada, and United Kingdom).
      METHODS: A review of relevant key documents regarding the HTA process was
      performed to develop the instrument which was then reviewed by selected HTAi
      members and revised. We identified and collected relevant information to map the
      level of HTA in the selected countries. This was supplemented by information from
      a structured survey among HTA experts in the selected countries (response rate:
      65/385). RESULTS: Mapping of HTA in a country can be done by focusing on the
      level of institutionalization and the HTA process (identification, priority
      setting, assessment, appraisal, reporting, dissemination, and implementation in
      policy and practice). Although HTA is most advanced in industrialized countries,
      there is a growing community in middle-income countries that uses HTA. For
      example, Brazil is rapidly developing effective HTA programs. India and Russia
      are at the very beginning of introducing HTA. The other middle-income countries
      show intermediate levels of HTA development compared with the reference
      countries. CONCLUSIONS: This study presents a set of indicators for documenting
      the current level and trends in HTA at country level. The findings can be used as
      a baseline measurement for future monitoring and evaluation. This will allow a
      variety of stakeholders to assess the development of HTA in their country, help
      inform strategies, and justify expenditure for HTA.

PMID- 24290338
TI  - Attitudes toward supplementary criteria in the reimbursement process in Poland.

PMID- 24290339
TI  - A model for HTA priority setting: experience in Lithuania.
AB  - OBJECTIVES: To promote the further development of HTA, this study aims to design
      a model for HTA priority setting, which would address national needs for a
      country with little experience in the field of HTA, and assess its feasibility
      for the health system. METHODS: Literature search and review, as well as
      qualitative research have been used in the design and testing of the model for
      HTA priority setting. To test the model and the methodology, a three-round Delphi
      study was conducted in 2011 in the form of an electronic questionnaire, which was
      distributed to the panel of eleven national experts. The panel was composed of
      experts representing various fields of the health care sector: policy-makers,
      health care service professionals and academics, with diverse professional roles.
      RESULTS: The designed model consists of four stages: (i) selection of experts for
      the panel, (ii) indication and selection of health policy topics, (iii)
      identification of health technologies, and (iv) priority setting. Three rounds of
      the Delphi study were performed to test the model and reach expert consensus on a
      list of health technologies for assessment, including pharmaceuticals, vaccines,
      medical devices, diagnostic methods, public health interventions, organizational
      systems, etc. CONCLUSIONS: Based on the Delphi technique as a method for
      consensus building, the model for HTA priority setting was developed for
      Lithuania; however, it could also be used for other countries with little
      experience in the field of HTA.

PMID- 24290337
TI  - Are value of information methods ready for prime time? An application to
      alternative treatment strategies for NSTEMI patients.
AB  - OBJECTIVES: The use of value of information methods to inform trial design has
      been widely advocated but there have been few empirical applications of these
      methods and there is little evidence they are widely used in decision making.
      This study considers the usefulness of value of information models in the context
      of a real clinical decision problem relating to alternative diagnostic strategies
      for patients with a recent non-ST elevated myocardial infarction. METHODS: A
      pretrial economic model is constructed to consider the cost-effectiveness of two
      competing strategies: coronary angiography alone or in conjunction with
      fractional flow reserve measurement. A closed-form solution to the expected
      benefits of information is used with optimal sample size estimated for a range of
      models reflecting increasingly realistic assumptions and alternative decision
      contexts. RESULTS: Fractional flow reserve measurement is expected to be cost
      effective with an incremental cost-effectiveness ratio of GBP 1,621, however,
      there is considerable uncertainty in this estimate and consequently a large
      expected value to reducing this uncertainty via a trial. The recommended sample
      size is strongly affected by the reality of the assumptions of the expected value
      of information (EVI) model and the decision context. CONCLUSIONS: Value of
      information models can provide a simple and flexible approach to clinical trial
      design and are more consistent with the constraints and objectives of the
      healthcare system than traditional frequentist approaches. However, the variation
      in sample size estimates demonstrates that it is essential that appropriate model
      parameters and decision contexts are used in their application.

PMID- 24290340
TI  - Which criteria are considered in healthcare decisions? Insights from an
      international survey of policy and clinical decision makers.
AB  - OBJECTIVES: The aim of this study was to gather qualitative and quantitative data
      on criteria considered by healthcare decision makers. METHODS: Using snowball
      sampling and an online questionnaire with forty-three criteria organized into ten
      clusters, decision makers were invited by an international task force to report
      which criteria they consider when making decisions on healthcare interventions in
      their context. Respondents reported whether each criterion is "currently
      considered," "should be considered," and its relative weight (scale 0-5).
      Differences in proportions of respondents were explored with inferential
      statistics across levels of decision (micro, meso, macro), decision maker
      perspectives, and world regions. RESULTS: A total of 140 decision makers (1/3
      clinical, 2/3 policy) from 23 countries in five continents completed the survey.
      The most relevant criteria (top ranked for "Currently considered," "Should be
      considered," and weights) were Clinical efficacy/effectiveness, Safety, Quality
      of evidence, Disease severity, and Impact on healthcare costs. Organizational and
      skill requirements were frequently considered but had relatively low weights. For
      almost all criteria, a higher proportion of decision makers reported that they
      "Should be considered" than that they are "Currently considered" (p < .05). For
      more than 74 percent of criteria, there were no statistical differences in
      proportions across levels of decision, perspectives and world regions.
      Statistically significant differences across several comparisons were found for:
      Population priorities, Stakeholder pressure/interests, Capacity to stimulate
      research, Impact on partnership and collaboration, and Environmental impact.
      CONCLUSIONS: Results suggest convergence among decision makers on the relevance
      of a core set of criteria and on the need to consider a wider range of criteria.
      Areas of divergence appear to be principally related to contextual factors.

PMID- 24290342
TI  - Closed loop obstruction: pictorial essay.
AB  - Closed loop obstruction occurs when a segment of bowel is incarcerated at two
      contiguous points. The diagnosis is based on multiple transitional zones. The
      incarcerated loops appear in U or C form or present a radial layout around the
      location of the obstruction. It's very important to specify the type of
      obstruction because, in patients with simple bowel obstruction, a conservative
      approach is often advised. On the other hand, a closed loop obstruction
      immediately requires a surgical approach because of its high morbidity and the
      risk of death in case of a late diagnosis. 

PMID- 24290343
TI  - Sitting comfortably versus lying down: is there really a difference in energy
      expenditure?
AB  - BACKGROUND & AIMS: Energy expenditure (EE) during sitting is widely assumed to be
      higher than that while lying down, but supporting evidence is equivocal. Despite
      this, resting EE in the sitting position is often used as a proxy for basal
      metabolic rate. Here we investigate whether EE differs in the comfortable seated
      position compared to supine (lying) position. METHODS: EE and respiratory
      quotient (RQ) were measured (by ventilated hood indirect calorimetry) in 19
      healthy subjects (9 men, 10 women) after an overnight fast. Supine measurements
      were made using a comfortable clinical tilting table and sitting measurements
      made using an adjustable, ergonomic car seat adapted for the hood system. After
      about 30 min of rest in either position, metabolic monitoring was conducted until
      stabilization of EE for at least 15 min in each posture. RESULTS: EE in the
      sitting position was not significantly different compared to supine (<2%
      difference). By contrast, heart rate was higher by 7 beats/min (p < 0.05). RQ was
      slightly but significantly decreased during sitting compared to lying (p < 0.05),
      with no change in breathing rate. CONCLUSIONS: This study suggests that the
      ventilated hood calorimetry system for assessment of REE after an overnight fast
      in a comfortable sitting position can be used as a good proxy of the basal
      metabolic rate. It also underscores the applicability of the ventilated hood
      system to measurements of resting EE in the sitting posture which, compared to
      supine posture, may be more acceptable/convenient to the subject/patient
      participating in postprandial metabolic studies lasting several hours.

PMID- 24290344
TI  - Omega 3:6 ratio intake and incidence of glaucoma: the SUN cohort.
AB  - BACKGROUND & AIMS: Omega 3 and omega 6 polyunsaturated fatty acids have been
      related to many diseases, especially to cardiovascular diseases. We aimed to
      assess the association between the intake of omega 3, omega 6 fatty acids and
      their ratio and the incidence of glaucoma in this prospective cohort study.
      METHODS: We followed-up 17,128 participants initially free of glaucoma for a
      median time of 8.2 years. Validated data of diet were collected at baseline with
      a 136-item semi-quantitative food-frequency questionnaire and information of new
      diagnosis of glaucoma in biennial follow-up questionnaires. Multivariable Cox
      regression models were fit to assess the relationship between omega 3, omega 6
      and their ratio and the incidence of glaucoma in the total sample and in
      participants aged >=40 years at baseline. RESULTS: During a median follow-up time
      of 8.2 years, 156 new cases of glaucoma were identified. No significant
      association was observed for the omega 3 or the omega 6 intake and the risk of
      glaucoma. Participants in the highest quintile of omega 3:6 ratio intake had a
      significantly higher risk of glaucoma than participants in the lowest quintile
      (hazard ratio (HR): 1.91 [95%CI: 1.05-3.46], p for trend 0.03). The association
      became stronger (HR for the comparison of the 5th versus the 1st quintile: 2.43
      [95%CI: 1.17-5.03], p for trend 0.02) when we considered only those participants
      who were >=40 years old. CONCLUSIONS: Our data suggest an association between
      omega 3:6 ratio intake and incident glaucoma in our cohort, especially among
      older participants.

PMID- 24290345
TI  - Additional oligofructose/inulin does not increase faecal bifidobacteria in
      critically ill patients receiving enteral nutrition: a randomised controlled
      trial.
AB  - BACKGROUND & AIMS: Patients with diarrhoea during enteral nutrition (EN) have
      been shown to have low faecal bifidobacteria concentrations. Oligofructose/inulin
      selectively stimulate the growth of bifidobacteria in healthy humans. This study
      investigates the effect of additional oligofructose/inulin on the
      gastrointestinal microbiota, short-chain fatty acids (SCFA) and faecal output in
      patients receiving EN. METHODS: Adult patients in the intensive care unit (ICU)
      who were starting EN with a formula containing fibre were randomised to receive 7
      g/d of additional oligofructose/inulin or an identically packaged placebo
      (maltodextrin). A fresh faecal sample was collected at baseline and following at
      least 7 days of supplementation. Faecal microbiota were analysed using
      fluorescent in-situ hybridisation and faecal output was monitored daily. RESULTS:
      Twenty-two patients (mean age 71 years) completed at least 7 days of intervention
      (mean 12 days). At the end of the intervention, there were no significant
      differences in the concentrations of bifidobacteria between the groups, after
      adjusting for baseline values (oligofructose/inulin 6.9 + 1.4, placebo 7.8 + 1.3
      log10 cells/g dry faeces, P > 0.05), but there were significantly lower
      concentrations of Faecalibacterium prausnitzii (7.0 + 1.0 vs. 8.4 + 1.3 log10
      cells/g, P = 0.01) and Bacteroides-Prevotella (9.1 + 1.0 vs. 9.9 + 0.9 log10
      cells/g, P = 0.05) in patients receiving additional oligofructose/inulin. There
      were no differences in faecal concentrations of any SCFA, secretory IgA, daily
      faecal score or incidence of diarrhoea between the two groups. CONCLUSIONS:
      Additional oligofructose/inulin did not increase faecal bifidobacteria in
      critically ill patients receiving EN, although it did result in lower
      concentrations of F. prausnitzii and Bacteroides-Prevotella. This trial is
      registered at http://controlled-trials.com. Identifier: ISRCTN06446184.

PMID- 24290347
TI  - Development of the medial hypothalamus: forming a functional hypothalamic
      neurohypophyseal interface.
AB  - The medial hypothalamus is composed of nuclei of the tuberal hypothalamus, the
      paraventricular nucleus of the anterior hypothalamus, and the neurohypophysis.
      Its arrangement, around the third ventricle of the brain, above the
      adenohypophysis, and in direct contact with the vasculature, means that it serves
      as an interface with circulating systems, providing a key conduit through which
      the brain can sample, and control, peripheral body systems. Through these
      interfaces, and interactions with other parts of the brain, the medial
      hypothalamus centrally governs diverse homeostatic processes, including energy
      and fluid balance, stress responses, growth, and reproductive behaviors. Here, we
      summarize recent studies that reveal how the diverse cell types within the medial
      hypothalamus are assembled in an integrated manner to enable its later function.
      In particular, we discuss how the temporally protracted operation of signaling
      pathways and transcription factors governs the appearance and regionalization of
      the hypothalamic primordium from the prosencephalic territory, the specification
      and differentiation of progenitors into neurons in organized nuclei, and the
      establishment of interfaces. Through analyses of mouse, chick, and zebrafish, a
      picture emerges of an evolutionarily conserved and highly coordinated
      developmental program. Early indications suggest that deregulation of this
      program may underlie complex human pathological conditions and dysfunctional
      behaviors, including stress and eating disorders. 

PMID- 24290348
TI  - Mammalian sex determination and gonad development.
AB  - From a developmental biology perspective, gonadogenesis is of particular interest
      because it provides a unique example of how distinct organs, the testis and
      ovary, can arise from a common bipotential primordium. Gonadogenesis is also
      highly relevant from a clinical perspective, as congenital disorders of sex
      development (DSDs) are not uncommon, occurring in approximately 1 in 4500 live
      births. In recent years, there has been significant progress in our understanding
      of the genes and pathways that control important aspects of gonadogenesis
      including the initial decision to develop as a testis or ovary (sex
      determination), elaboration and cross-repression of the testis and ovary
      developmental pathways, and maintenance of the gonadal phenotype after birth. In
      this chapter, we provide an overview of gonadal morphogenesis and cell lineage
      specification, focusing primarily on these processes in mice and humans. We also
      provide an update on the genetic mechanisms that control murine gonadogenesis and
      maintenance and, where possible, discuss new insights into the pathological
      mechanisms of DSDs associated with mutation of orthologous genes in mice and
      humans. 

PMID- 24290349
TI  - Mechanisms of thyroid development and dysgenesis: an analysis based on
      developmental stages and concurrent embryonic anatomy.
AB  - Thyroid dysgenesis is the most common cause of congenital hypothyroidism that
      affects 1 in 3000 newborns. Although a number of pathogenetic mutations in
      thyroid developmental genes have been identified, the molecular mechanism of
      disease is unknown in most cases. This chapter summarizes the current knowledge
      of normal thyroid development and puts the different developmental stages in
      perspective, from the time of foregut endoderm patterning to the final shaping of
      pharyngeal anatomy, for understanding how specific malformations may arise. At
      the cellular level, we will also discuss fate determination of follicular and C
      cell progenitors and their subsequent embryonic growth, migration, and
      differentiation as the different thyroid primordia evolve and merge to establish
      the final size and shape of the gland. 

PMID- 24290351
TI  - From pancreas morphogenesis to beta-cell regeneration.
AB  - Type 1 diabetes is a metabolic disease resulting in the selective loss of
      pancreatic insulin-producing beta-cells and affecting millions of people
      worldwide. The side effects of diabetes are varied and include cardiovascular,
      neuropathologic, and kidney diseases. Despite the most recent advances in
      diabetes care, patients suffering from type 1 diabetes still display a shortened
      life expectancy compared to their healthy counterparts. In an effort to improve
      beta-cell-replacement therapies, numerous approaches are currently being pursued,
      most of these aiming at finding ways to differentiate stem/progenitor cells into
      beta-like cells by mimicking embryonic development. Unfortunately, these efforts
      have hitherto not allowed the generation of fully functional beta-cells. This
      chapter summarizes recent findings, allowing a better insight into the molecular
      mechanisms underlying the genesis of beta-cells during the course of pancreatic
      morphogenesis. Furthermore, a focus is made on new research avenues concerning
      the conversion of pre-existing pancreatic cells into beta-like cells, such
      approaches holding great promise for the development of type 1 diabetes
      therapies. 

PMID- 24290350
TI  - The pineal gland from development to function.
AB  - The pineal gland is a small neuroendocrine organ whose main and most conserved
      function is the nighttime secretion of melatonin. In lower vertebrates, the
      pineal gland is directly photosensitive. In contrast, in higher vertebrates, the
      direct photosensitivity of the pineal gland had been lost. Rather, the action of
      this gland as a relay between environmental light conditions and body functions
      involves reception of light information by the retina. In parallel to this
      sensory regression, the pineal gland (and its accessory organs) appears to have
      lost several functions in relation to light and temperature, which are important
      in lower vertebrate species. In humans, the functions of the pineal gland overlap
      with the functions of melatonin. They are extremely widespread and include
      general effects both on cell protection and on more precise functions, such as
      sleep and immunity. Recently, the role of melatonin has received a considerable
      amount of attention due to increased cancer risk in shift workers and the
      discovery that patients suffering from neurodegenerative diseases, autism, or
      depression exhibit abnormal melatonin rhythms. 

PMID- 24290352
TI  - Adrenocortical development, maintenance, and disease.
AB  - The adrenal gland controls a plethora of crucial physiological functions, and
      dysfunction is associated with severe morbidity. Because of the vital importance
      of appropriate adrenal function, the development and function of the gland have
      been intensively studied, and these investigations have revealed fascinating
      developmental origins and a remarkable remodeling and regenerative capacity in
      the adult. This chapter, focusing on the adrenal cortex, will describe our
      current understanding of the development and maintenance of the adrenal gland,
      which has been advanced over recent years by the use of sophisticated genetic
      models in the study of both normal function and disease. This work has shed light
      on the transcriptional networks and signaling pathways involved in development
      and maintenance of the gland and in its pathology; these are discussed in the
      light of the wealth of physiological information gathered in studies of human and
      rodent adrenal development and function. 

PMID- 24290346
TI  - Pituitary gland development and disease: from stem cell to hormone production.
AB  - Many aspects of pituitary development have become better understood in the past
      two decades. The signaling pathways regulating pituitary growth and shape have
      emerged, and the balancing interactions between the pathways are now appreciated.
      Markers for multipotent progenitor cells are being identified, and signature
      transcription factors have been discovered for most hormone-producing cell types.
      We now realize that pulsatile hormone secretion involves a 3D integration of
      cellular networks. About a dozen genes are known to cause pituitary hypoplasia
      when mutated due to their essential roles in pituitary development. Similarly, a
      few genes are known that predispose to familial endocrine neoplasia, and several
      genes mutated in sporadic pituitary adenomas are documented. In the next decade,
      we anticipate gleaning a deeper appreciation of these processes at the molecular
      level, insight into the development of the hypophyseal portal blood system, and
      evolution of better therapeutics for congenital and acquired hormone deficiencies
      and for common craniopharyngiomas and pituitary adenomas. 

PMID- 24290354
TI  - A germline oncogenic MITF mutation and tumor susceptibility.
AB  - MITF (Microphthalmia-associated transcription factor) is a lineage specific
      transcription factor that plays a critical role in melanocyte homeostasis and
      whose deregulation has been shown to contribute to melanoma disease. A germline
      mutation in MITF, impairing SUMOylation and predisposing to cutaneous malignant
      melanoma, was recently identified. Interestingly, an association of the MITF
      mutation with coexisting melanoma and renal cell carcinoma was also shown.
      Collectively, these data suggest that MITF has an important oncogenic function in
      tumorigenesis of multiple tissues/melanocytes and kidney cells. 

PMID- 24290355
TI  - Effect of head size on wear properties of metal-on-metal bearings of hip
      prostheses, and comparison with wear properties of metal-on-polyethylene bearings
      using hip simulator.
AB  - The effects of articular head size on the wear losses of the metal insert and
      articular head for a metal-on-metal bearing were examined using a hip simulator
      manufactured to satisfy ISO 14242-1. The wear properties of metal-on-metal and
      metal-on-polyethylene bearings were also compared under the same conditions. The
      total wear losses of the metal insert and articular head decreased with
      increasing diameter of the metal insert in the range from 28 to 44mm. The total
      wear loss was greater for a diameter of 48mm than for a diameter of 44mm. When
      the articular metal insert diameter was smaller than 44mm, the wear loss was
      reduced because the contact surface pressure increased with increasing metal
      insert diameter. However, the increase in wear loss observed for the 48-mm
      diameter insert might have been due to the considerable increase in the rotation
      moment with increasing insert diameter. The tendency of decreasing contact
      pressure calculated using the Hertzian contact stress equation nearly conformed
      to the change in wear loss. On the other hand, the wear loss of an artificial hip
      joint consisting of a cross-linked ultrahigh-molecular-weight polyethylene insert
      (UHMWPE) and a Co-Cr-Mo articular head was small. 

PMID- 24290356
TI  - Spectroscopic, electrochemical, and alkylation reactions: tert-butyl N-(2
      mercaptoethyl)carbamate copper(II) and nickel(II) complexes as structural mimics
      for the active site of thiolate-alkylating enzymes.
AB  - Two new dithiolate copper(II) and nickel(II) complexes with the ligand tert-butyl
      N-(2-mercaptoethyl)-carbamate (Boc-SH) were prepared. Their structures were
      established to be [(Boc-S)2M], where M=Cu (1) and Ni (2) by using elemental
      analysis, thermal analysis, molar conductivity, FT-IR, Raman, UV/VIS, and ESR as
      well as EI-mass spectroscopic methods. The X-ray structure of the ligand Boc-SH
      was also determined. Spectral data showed that the carbamate ligand act as
      anioinic bidentate through one immine nitrogen and one thiolate sulfur donor
      atoms. The spectral techniques suggest that both complexes appear to have square
      planar geometries. The very low electrical conductance of the two complexes
      supports their neutral nature. The redox behaviors of the obtained complexes were
      also investigated by cyclic voltammetry. The monomeric nature of both complexes
      was assessed from their magnetic susceptibility values. The thermoanalytical data
      evidence that complex (2) is stable up to 165 degrees C and undergo complete
      decomposition, resulting in NiO as a residual product. The TEM image of the
      obtained oxide residue showed its nanosize cluster, suggesting that complex (2)
      may be used as a precursor for the formation of nanooxide. The methylation
      reactions of the two dithiolate complexes (1) and (2) with methyl iodide appear
      to occur intramolecularly at the metal(II)-bound dithiolates, forming the
      metal(II)-bound dithioether complexes [M(Boc-SCH3)2]I2 with clean second-order
      constants of 7.95*10(-2) and 10.59*10(-2) M(-1) s(-1), respectively.

PMID- 24290357
TI  - Can the electronegativity equalization method predict spectroscopic properties?
AB  - The electronegativity equalization method is classically used as a method
      allowing the fast generation of atomic charges using a set of calibrated
      parameters and provided knowledge of the molecular structure. Recently, it has
      started being used for the calculation of other reactivity descriptors and for
      the development of polarizable and reactive force fields. For such applications,
      it is of interest to know whether the method, through the inclusion of the
      molecular geometry in the Taylor expansion of the energy, would also allow
      sufficiently accurate predictions of spectroscopic data. In this work, relevant
      quantities for IR spectroscopy are considered, namely the dipole derivatives and
      the Cartesian Hessian. Despite careful calibration of parameters for this
      specific task, it is shown that the current models yield insufficiently accurate
      results. 

PMID- 24290358
TI  - Genetically encoded chemical probes in cells reveal the binding path of urocortin
      I to CRF class B GPCR.
AB  - Molecular determinants regulating the activation of class B G-protein-coupled
      receptors (GPCRs) by native peptide agonists are largely unknown. We have
      investigated here the interaction between the corticotropin releasing factor
      receptor type 1 (CRF1R) and its native 40-mer peptide ligand Urocortin-I directly
      in mammalian cells. By incorporating unnatural amino acid photochemical and new
      click-chemical probes into the intact receptor expressed in the native membrane
      of live cells, 44 intermolecular spatial constraints have been derived for the
      ligand-receptor interaction. The data were analyzed in the context of the
      recently resolved crystal structure of CRF1R transmembrane domain and existing
      extracellular domain structures, yielding a complete conformational model for the
      peptide-receptor complex. Structural features of the receptor-ligand complex
      yield molecular insights on the mechanism of receptor activation and the basis
      for discrimination between agonist and antagonist function.

PMID- 24290359
TI  - Isogenic human iPSC Parkinson's model shows nitrosative stress-induced
      dysfunction in MEF2-PGC1alpha transcription.
AB  - Parkinson's disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons
      in the substantia nigra pars compacta (SNpc). An association has been reported
      between PD and exposure to mitochondrial toxins, including environmental
      pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived
      stem cell model of PD allowing comparison of A53T alpha-synuclein (alpha-syn)
      mutant cells and isogenic mutation-corrected controls, we identify mitochondrial
      toxin-induced perturbations in A53T alpha-syn A9 DA neurons (hNs). We report a
      pathway whereby basal and toxin-induced nitrosative/oxidative stress results in S
      nitrosylation of transcription factor MEF2C in A53T hNs compared to corrected
      controls. This redox reaction inhibits the MEF2C-PGC1alpha transcriptional
      network, contributing to mitochondrial dysfunction and apoptotic cell death. Our
      data provide mechanistic insight into gene-environmental interaction (GxE) in the
      pathogenesis of PD. Furthermore, using small-molecule high-throughput screening,
      we identify the MEF2C-PGC1alpha pathway as a therapeutic target to combat PD. 

PMID- 24290361
TI  - A novel ALK rearrangement in an inflammatory myofibroblastic tumor in a neonate.
AB  - Inflammatory myofibroblastic tumors (IMTs) are uncommon lesions primarily
      affecting children and young adults. They have rarely been described in infants,
      with a very small number described in neonates. Structural rearrangements in the
      anaplastic large-cell lymphoma kinase gene (ALK) has contributed to our
      categorizing this lesion as a neoplasm. In addition, rearrangements of the ALK
      gene have been implicated in the pathogenicity of many other hematolymphoid and
      non-hematolymphoid tumors, typically involving 2p23 with different partners or
      with pericentric inversion. We report a previously undescribed cryptic deletion
      and intrachromosomal-insertional translocation of the 3'-region of the ALK gene
      from 2p23 to the 2q33-q35 in an IMT of a newborn patient with an apparently
      normal G-band karyotype of the tumor.

PMID- 24290360
TI  - MUC2 expression is an adverse prognostic factor in superficial gastroesophageal
      adenocarcinomas.
AB  - Mucin core proteins (MUCs) are expressed in tissue-specific patterns in the
      gastrointestinal tract and expression is deregulated in Barrett's metaplasia.
      Based on differential expression, MUCs have been used to classify adenocarcinomas
      into distinct phenotypes (eg, intestinal, gastric, pancreaticobiliary, etc).
      Because MUC expression patterns carry prognostic significance in other tumors, we
      evaluated MUC expression in superficial adenocarcinomas of the gastroesophageal
      junction and esophagus (EAC) to determine whether there are differences in
      outcome associated with MUC subtype in this potentially curable subset of EAC. We
      classified 142 resected, superficial (T1) EAC based on their pattern of
      expression of MUC2, MUC5AC, MUC6 and MUC1. The association between survival and
      MUC expression pattern was determined in univariate and multivariate analyses.
      The MUC2 positive "intestinal" phenotype was associated with significantly worse
      prognosis in submucosal EAC (hazard ratio 2.2, 95% confidence interval 1.2-4.2),
      independent of node stage and other prognostic factors. MUC2 expression in
      submucosal EAC also showed significantly accelerated time to recurrence (hazard
      ratio 2.8, 95% confidence interval 1.2-6.8) after adjusting for node stage. The
      classification of superficial EAC by MUC protein expression has prognostic
      significance. MUC2 expression is an adverse prognostic indicator in submucosal
      EAC, independent of node stage and other prognostic factors. 

PMID- 24290362
TI  - Crossing the frontier: a hypothesis for the origins of meristic constraint in
      mammalian axial patterning.
AB  - Serially homologous systems with high internal differentiation frequently exhibit
      meristic constraints, although the developmental basis for constraint is unknown.
      Constraints in the counts of the cervical and lumbosacral vertebral series are
      unique to mammals, and appeared in the Triassic, early in their history.
      Concurrent adaptive modifications of the mammalian respiratory and locomotor
      systems involved a novel source of cells for muscularization of the diaphragm
      from cervical somites, and the loss of ribs from lumbar vertebrae. Each of these
      innovations increased the modularity of the somitic mesoderm, and altered somitic
      and lateral plate mesodermal interactions across the lateral somitic frontier.
      These developmental innovations are hypothesized here to constrain the
      anteroposterior transposition of the limbs along the column, and thus also
      cervical and thoracolumbar count. Meristic constraints are therefore regarded
      here as the nonadaptive, secondary consequences of adaptive respiratory and
      locomotor traits. 

PMID- 24290363
TI  - Behavioral responses of batoid elasmobranchs to prey-simulating electric fields
      are correlated to peripheral sensory morphology and ecology.
AB  - Electrosensory pore number, distribution, and sensitivity to prey-simulating
      electric fields have been described for many shark species. Electrosensory
      systems in batoids have received much less attention. Pore number and
      distribution have yet to be correlated to differences in sensitivity. However,
      pore number, pore distribution and sensitivity have been linked to behavior,
      diet, and morphology and follow species-specific trends. We report here that
      cownose rays have a greater number of pores than the yellow stingray, most of
      which are concentrated on the anterior ventral surface for both species. However,
      yellow stingrays have a broader arrangement of pores on both their dorsal and
      ventral surfaces than the cownose rays. Yellow stingrays demonstrated a median
      behavioral sensitivity to weak electric fields of 22nVcm(-1) and are among the
      most highly sensitive batoids studied to date. Cownose rays are less sensitive
      than all other elasmobranch species with a median sensitivity of 107nVcm(-1). As
      reported in previous studies, a higher pore number did not result in greater
      sensitivity. Cownose rays are benthopelagic schooling rays and may benefit from
      reduced sensitivity to bioelectric fields when they are surrounded by the
      bioelectric fields of conspecifics. Yellow stingrays, on the other hand, are
      typically solitary and bury in the substrate. A greater number of pores on their
      dorsal surface might improve detection of predators above them. Also, increased
      sensitivity and a broader distribution of pores may be beneficial as small prey
      items move past a buried ray. 

PMID- 24290364
TI  - The investigation and differential diagnosis of Asperger syndrome in adults.
AB  - BACKGROUND: As a result of the increased public interest in autism spectrum
      disorders (ASD), certain core manifestations of ASD--impaired social interaction
      and communication, bizarre interests--are now commonly recognized as being
      typical of autism, not only in children, but in adults as well. More often than
      before, general practitioners, neurologists, and psychiatrists find themselves
      being asked whether a patient is suffering from previously unrecognized Asperger
      syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of
      diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic
      evaluation of AS in adulthood. METHOD: We selectively searched the Medline
      database for pertinent literature, paying special attention to diagnostic manuals
      and to the guideline of the United Kingdom's National Institute for Health and
      Care Excellence (NICE). RESULTS: Centrally important aspects of the diagnosis of
      AS include an assessment of the patient's ability to assume the emotional
      perspectives of others, non-verbal modes of expression, repetitive behavior
      patterns, and childhood social behavioral history. The autism quotient (AQ) is
      now established as a simple but nonspecific screening test. Up to 70% of all
      affected adults have comorbid disturbances, most often depression and anxiety
      disorders. The differential diagnosis includes personality disorders, anxiety
      disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity
      disorder. The diagnostic assessment should proceed in stepwise fashion, starting
      from simple screening in primary care and then moving on to evaluation of the
      suspected diagnosis by a mental health care specialist, followed by extensive
      further investigation in an outpatient clinic specifically devoted to patients
      with autism spectrum disorders. CONCLUSION: The diagnostic assessment of autism
      in adults requires knowledge of the core and accompanying manifestations of
      autism and of their differential diagnoses. More research is needed for the
      development of further screening tests and the precise determination of diagnosis
      rates, differential diagnoses, nd comorbidities.

PMID- 24290365
TI  - The febrile child: diagnosis and treatment.
AB  - BACKGROUND: Fever accounts for 70% of all consultations with pediatricians and
      family physicians. Fever without an identifiable cause (<7 days' duration) and
      fever of unknown origin (FUO, >= 7 days' duration) are particularly challenging
      clinical situations. METHOD: This article is based on a selective literature
      search for publications containing the term "pediatric fever management," with
      special attention to meta-analyses and systematic reviews. RESULTS: The mainstay
      of diagnosis is physical examination by a physician who is experienced in the
      care of children and adolescents. The frequency of severe bacterial infection
      (SBI) is about 10% in neonates, 5% in babies aged up to 3 months, and 0.5% to 1%
      in older infants and toddlers. The mortality of SBI in neonates is about 10%.
      Both the degree of the parents' and the physician's concern are important warning
      signs for SBI. Clinical signs of SBI include cyanosis, tachypnea, poor peripheral
      perfusion, petechiae, and a rectal temperature above 40 degrees C. Antipyretic
      drugs should only be used in special, selected situations. More than 40% of cases
      of FUO are due to infection; in more than 30% of cases, the cause is never
      determined. CONCLUSION: Aspects of central importance include the repeated
      physical examination of the patient, and parent counseling and education of
      medical and nursing staff pertaining to the warning signs for SBI. Research is
      needed in the areas of diagnostic testing and the development of new vaccines.

PMID- 24290368
TI  - New concept of the contraction-extension property of the left ventricular
      myocardium.
AB  - OBJECTIVES: Using newly developed ultrasonic technology, we attempted to disclose
      the characteristics of the left ventricular (LV) contraction-extension (C-E)
      property, which has an important relationship to LV function. METHODS: Strain
      rate (SR) distribution within the posterior wall and interventricular septum was
      microscopically measured with a high accuracy of 821MUm in spatial resolution by
      using the phase difference tracking method. The subjects were 10 healthy men
      (aged 30-50 years). RESULTS: The time course of the SR distribution disclosed the
      characteristic C-E property, i.e. the contraction started from the apex and
      propagated toward the base on one hand, and from the epicardial side toward the
      endocardial side on the other hand. Therefore, the contraction of one area and
      the extension of another area simultaneously appeared through nearly the whole
      cardiac cycle, with the contracting part positively extending the latter part and
      vice versa. The time course of these propagations gave rise to the peristalsis
      and the bellows action of the LV wall, and both contributed to effective LV
      function. The LV contraction started coinciding in time with the P wave of the
      electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2
      types of transitional phase, as well as the ejection phase and slow filling
      phase. The sum of the measurement time duration of either the contraction or the
      extension process occupied nearly equal duration in normal conditions.
      CONCLUSION: The newly developed ultrasonic technology revealed that the SR
      distribution was important in evaluating the C-E property of the LV myocardium.
      The harmonious succession of the 4 cardiac phases newly identified seemed to be
      helpful in understanding the mechanism to keep long-lasting pump function of the
      LV.

PMID- 24290366
TI  - Availability of tobacco products associated with use of marijuana cigars
      (blunts).
AB  - OBJECTIVES: This study examines factors associated with availability of tobacco
      products for marijuana cigars (i.e., blunts) in 50 non-contiguous mid-sized
      California communities. METHODS: The study is based on data collected in 943
      tobacco outlets. Neighborhood demographics, community adult marijuana prevalence,
      medical marijuana policy and access to medical marijuana dispensaries and
      delivery services were included. RESULTS: Multilevel logistic regression analyses
      indicated that compared with small markets, availability of tobacco products
      associated with use of blunts was significantly higher in convenience stores,
      smoke/tobacco shops and liquor stores. None of the neighborhood demographics were
      associated with availability of blunt wrappers and only a small percent of Whites
      was positively associated with availability of blunt cigars, small cigars or
      cigarillos at the store. Controlling for outlet type and neighborhood
      demographics, higher city prevalence of adult marijuana use was associated with
      greater availability of blunt wrappers. Also, policy that permits medical
      marijuana dispensaries or private cultivation was positively associated with
      availability of tobacco products for blunts. Density of medical marijuana
      dispensaries and delivery services, however, was negatively associated with
      greater availability of these products at tobacco outlets. CONCLUSIONS: Results
      suggest that availability of tobacco products associated with blunts is similar
      in neighborhoods with different socioeconomic status and racial and ethnic
      composition. Results also suggest the important role that community norms that
      support marijuana use or legalization of medical marijuana and medical marijuana
      policy may play in increasing availability of tobacco products associated with
      blunts.

PMID- 24290367
TI  - Brain-derived neurotrophic factor levels in late-life depression and comorbid
      mild cognitive impairment: a longitudinal study.
AB  - Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the
      pathophysiology of cognitive decline in depression and neurodegenerative
      disorders in older adults. We aimed to evaluate the longitudinal association over
      two years between BDNF and persistent cognitive decline in individuals with
      remitted late-life depression and Mild Cognitive Impairment (LLD + MCI) compared
      to either individuals with remitted LLD and no cognitive decline (LLD + NCD) or
      never-depressed, cognitively normal, elderly control participants. We
      additionally evaluated the effect of double-blind, placebo-controlled donepezil
      treatment on BDNF levels in all of the remitted LLD participants (across the
      levels of cognitive function). We included 160 elderly participants in this study
      (72 LLD + NCD, 55 LLD + MCI and 33 never-depressed cognitively normal elderly
      participants). At the same visits, cognitive assessments were conducted and blood
      sampling to determine serum BDNF levels were collected at baseline assessment and
      after one and two years of follow-up. We utilized repeated measure, mixed effect
      models to assess: (1) the effects of diagnosis (LLD + MCI, LLD + NCD, and
      controls), time, and their interaction on BDNF levels; and (2) the effects of
      donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD + MCI
      vs. LLD + NCD), and interactions between these contrasts on BDNF levels. We found
      a significant effect of time on BDNF level (p = 0.02) and a significant decline
      in BDNF levels over 2 years of follow-up in participants with LLD + MCI (p =
      0.004) and controls (p = 0.04). We found no effect of donepezil treatment on BDNF
      level. The present results suggest that aging is an important factor related to
      decline in BDNF level. Clinicaltrials.gov Identifier: NCT00177671. 

PMID- 24290370
TI  - FDG-PET-CT is effective in selecting patients with poor long term survivals for
      colorectal liver metastases.
AB  - AIMS: Having incorporated PET-CT as part of the staging process for colorectal
      liver metastases (CRLM) in our unit since 2008, this study aims to evaluate the
      survival outcomes of all patients managed by our specialist multi-disciplinary
      team (MDT). METHODS: All patients with colorectal liver metastases referred to a
      single liver MDT between 2008 and 2011 were examined. Overall survival (OS) for
      palliative groups due to occult extrahepatic disease detected by PET-CT (A) and
      those upfront palliative patients with extensive multi-site disease as identified
      on baseline CT or disease progression during chemotherapy (B), and resected (C)
      groups were evaluated and compared. Different extents of occult extrahepatic
      disease as characterised by PET-CT were also compared. RESULTS: 532 patients were
      included in the study. Median OS for group A (n = 80), B (n = 161) and C (n =
      291) were 10.9, 12.0 and 46.7 months, with a 5-year OS approaching 6.5%, 6.1% and
      43.0% respectively. There were significant differences in OS of C vs. A & B (p <
      0.001). Single compartment metastases had a significant better survival outcomes
      than non-torso metastases (p = 0.04). CONCLUSION: This is the first report of OS
      of patients with CRLM excluded from surgery on the basis of PET-CT. We have
      confirmed that PET-CT is effective in selecting patients with occult extrahepatic
      disease, which has poor survival outcomes. However, a subgroup with single
      compartment extrahepatic disease has a better than expected outcome.

PMID- 24290371
TI  - Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of
      randomized trials.
AB  - INTRODUCTION: An important component of treatment failure in gastric cancer (GC)
      is cancer dissemination within the peritoneal cavity and nodal metastasis.
      Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute
      in treating advanced GC. The purpose of the study is to investigate the effects
      of IPC in patients with advanced GC. MATERIAL AND METHODS: A systematic review
      with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs.
      control in patients with advanced GC was performed. RESULTS: Twenty prospective
      RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into
      control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27,
      0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal
      metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in
      patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate
      was increased by surgery + IPC (OR = 1.82). The overall recurrence and the
      peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47
      respectively). There was no statistically significant difference in lymph-nodal
      recurrence rate. The rate of haematogenous metastasis was improved by surgery +
      IPC (OR = 0.63). CONCLUSIONS: 1, 2 and 3-year overall survival is incremented by
      the IPC. No differences have been found at 5-year in overall survival rate. 2 and
      3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality
      rates in patients with serosal infiltration are improved by the use of IPC. IPC
      has positive effect on peritoneal recurrence and distant metastasis. Morbidity
      rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients
      affected by advanced gastric cancer is not a contraindication to IPC.

PMID- 24290373
TI  - Early pregnancy diagnosis in sheep using near-infrared spectroscopy on blood
      plasma.
AB  - The objective of this study was to evaluate the ability of near-infrared
      reflectance spectroscopy (NIRS) to discriminate between pregnant and nonpregnant
      ewes in early stages of pregnancy after artificial insemination (AI) from blood
      plasma. Samples were collected using jugular puncture at 18 and 25 days after AI
      from 188 Rasa Aragonesa and Ansotana ewes. Plasma samples were analyzed for
      pregnancy-associated glycoprotein (PAG) and progesterone (P4) using ELISA
      commercial kits. The spectra of plasma samples were recorded in the visible and
      near-infrared ranges. The performance of these tests were compared, using as
      criterion standard the pregnancy status determined using transabdominal
      ultrasonography at 45 days after AI. Pregnancy rate was 47.9% (90/188). At Day
      18, sensitivity was similar in NIRS and P4 tests (98.9% vs. 100%; not
      significant) and greater than PAG (32.2%; both P < 0.001). Specificity was
      similar in NIRS and PAG tests (both 100%) and greater than that of P4 (84.7%; P <
      0.001). At Day 25, sensitivity and specificity of NIRS and PAG were both 100%. It
      can be concluded that NIRS was an accurate method of diagnosis of pregnancy at
      Days 18 and 25 after AI in ewes. 

PMID- 24290372
TI  - MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is
      downregulated in hepatocellular carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate
      physiological and pathological processes by suppressing target gene expression.
      Altered expression of miR-30a-3p has been demonstrated in several cancers.
      However, little about how miR-30a-3p functions in these cancers has been
      reported, and the role of miR-30a-3p in hepatocellular carcinoma (HCC) is
      unknown. The purpose of this study was to identify the role and underlying
      molecular mechanism of action of miR-30a-3p in HCC. METHODS: A total of 110 HCC
      patients, primarily treated by surgical removal of tumors, were involved in the
      study. HCC cell line Bel-7402 was selected to characterize the function of miR
      30a-3p in vitro. RESULTS: Our results showed that in 83.6% of the 110 HCC
      patients, expression of miR-30a-3p was significantly downregulated (P < 0.0001)
      in tumors compared to adjacent normal tissues. In a clinicopathological
      correlation analysis, downregulation of miR-30a-3p correlated with a
      significantly higher incidence of portal vein tumor thrombus (PVTT, P = 0.009).
      Moreover, miR-30a-3p markedly inhibited the invasion and migration of Bel-7402
      HCC cells in vitro. Furthermore, miR-30a-3p overexpression had an inhibitory
      effect on cell proliferation, induced apoptosis and increased arrest of cells in
      the S phase. We further demonstrated that miR-30a-3p regulates HCC cell function
      by a mechanism involving reduced vimentin and MMP3 expression and restoration of
      E-cadherin expression. CONCLUSIONS: our data suggest that miR-30a-3p is
      downregulated in HCC and acts as a tumor suppressor in vitro. Regulation of
      vimentin, E-cadherin and MMP3 by miR-30a-3p suggests a useful therapeutic
      strategy for tumors with reduced miR-30a-3p expression.

PMID- 24290374
TI  - Postthaw survival of in vitro-produced bovine blastocysts loaded onto the inner
      surface of a plastic vitrification straw.
AB  - In this study, we investigated whether vitrification of an embryo by attachment
      to the inner surface of a plastic straw, which requires a small volume of
      vitrification solution, improves the survival of thawed embryos. In vitro
      produced Korean native cattle blastocysts were randomly assigned into four
      groups: (1) blastocysts attached to the inner surface of a plastic straw (aV);
      (2) blastocysts loaded into the column of a plastic straw (cV); (3) blastocysts
      directly dropped into liquid nitrogen (dV); and (4) nonvitrified blastocysts
      (control). The postthaw recovery rate did not significantly differ among the aV,
      dV, and cV groups (98.3% vs. 81.5% vs. 91.4%). The postthaw survival rate was
      greater in the control, aV, and dV groups than in the cV group (100%, 87.7%, and
      81.8% vs. 26.4%, P < 0.05), but did not significantly differ among the control,
      aV, and dV groups. The total number of cells per blastocyst did not significantly
      differ among the groups (134.4 +/- 38.9 in control vs. 114 +/- 48.1 in aV, 105.6
      +/- 33.9 in dV, and 102 +/- 35.1 in cV group). However, the number of apoptotic
      cells per blastocyst was higher in the dV and cV groups than in the control group
      (10.9 +/- 9.6 and 14.5 +/- 9.5 vs. 0.4 +/- 1.4; P < 0.05), but did not
      significantly differ between the control and aV groups (0.4 +/- 1.4 vs. 6.6 +/-
      9.5). In addition, the blastocoel of each blastocyst was left intact or was
      mechanically punctured to reduce its volume, and the blastocysts were then
      vitrified using the aV method. At 12 hours after thawing, the re-expansion rate
      did not significantly differ among the control, punctured aV, and nonpunctured aV
      groups (93.3% vs. 85.2% vs. 82.8%). However, at 24 hours after thawing, the
      hatching rate was greater in the control and punctured aV groups than in the
      nonpunctured aV group (75% and 62.9% vs. 37.1%; P < 0.05). The total number of
      cells per blastocyst was greater in the control group than in the nonpunctured aV
      group (143 +/- 37.2 vs. 94.5 +/- 18.6; P < 0.05), but did not significantly
      differ between the control and punctured aV groups (143 +/- 37.2 vs. 119.4 +/-
      19.7). The number of apoptotic cells per blastocyst was greater in the
      nonpunctured aV group than in the control and punctured aV groups (11.3 +/- 6.1
      vs. 5.9 +/- 5.8 and 6.3 +/- 4.4; P < 0.05). Taken together, the data show that
      the aV method improved the survival and quality of vitrified-thawed blastocysts.
      Furthermore, puncture of the blastocoel increased the hatching rate and reduced
      the number of apoptotic cells in vitrified-thawed blastocysts generated using the
      aV method.

PMID- 24290375
TI  - SAMS, a syndrome of short stature, auditory-canal atresia, mandibular hypoplasia,
      and skeletal abnormalities is a unique neurocristopathy caused by mutations in
      Goosecoid.
AB  - Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal
      abnormalities (SAMS) has been reported previously to be a rare, autosomal
      recessive developmental disorder with other, unique rhizomelic skeletal
      anomalies. These include bilateral humeral hypoplasia, humeroscapular synostosis,
      pelvic abnormalities, and proximal defects of the femora. To identify the genetic
      basis of SAMS, we used molecular karyotyping and whole-exome sequencing (WES) to
      study small, unrelated families. Filtering of variants from the WES data included
      segregation analysis followed by comparison of in-house exomes. We identified a
      homozygous 306 kb microdeletion and homozygous predicted null mutations of GSC,
      encoding Goosecoid homeobox protein, a paired-like homeodomain transcription
      factor. This confirms that SAMS is a human malformation syndrome resulting from
      GSC mutations. Previously, Goosecoid has been shown to be a determinant at the
      Xenopus gastrula organizer region and a segment-polarity determinant in
      Drosophila. In the present report, we present data on Goosecoid protein
      localization in staged mouse embryos. These data and the SAMS clinical phenotype
      both suggest that Goosecoid is a downstream effector of the regulatory networks
      that define neural-crest cell-fate specification and subsequent mesoderm cell
      lineages in mammals, particularly during shoulder and hip formation. Our findings
      confirm that Goosecoid has an essential role in human craniofacial and joint
      development and suggest that Goosecoid is an essential regulator of mesodermal
      patterning in mammals and that it has specific functions in neural crest cell
      derivatives. 

PMID- 24290376
TI  - Disruption of autoregulatory feedback by a mutation in a remote, ultraconserved
      PAX6 enhancer causes aniridia.
AB  - The strictly regulated expression of most pleiotropic developmental control genes
      is critically dependent on the activity of long-range cis-regulatory elements.
      This was revealed by the identification of individuals with a genetic condition
      lacking coding-region mutations in the gene commonly associated with the disease
      but having a variety of nearby chromosomal abnormalities, collectively described
      as cis-ruption disease cases. The congenital eye malformation aniridia is caused
      by haploinsufficiency of the developmental regulator PAX6. We discovered a de
      novo point mutation in an ultraconserved cis-element located 150 kb downstream
      from PAX6 in an affected individual with intact coding region and chromosomal
      locus. The element SIMO acts as a strong enhancer in developing ocular
      structures. The mutation disrupts an autoregulatory PAX6 binding site, causing
      loss of enhancer activity, resulting in defective maintenance of PAX6 expression.
      These findings reveal a distinct regulatory mechanism for genetic disease by
      disruption of an autoregulatory feedback loop critical for maintenance of gene
      expression through development. 

PMID- 24290377
TI  - Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding
      variants in type 2 diabetes.
AB  - It has been hypothesized that, in aggregate, rare variants in coding regions of
      genes explain a substantial fraction of the heritability of common diseases. We
      sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes
      (including body mass index > 27.5 kg/m(2) and hypertension) and 1,000 healthy
      controls to an average depth of 56*. Our simulations suggest that our study had
      the statistical power to detect at least one causal gene (a gene containing
      causal mutations) if the heritability of these common diseases was explained by
      rare variants in the coding regions of a limited number of genes. We applied a
      series of gene-based tests to detect such susceptibility genes. However, no gene
      showed a significant association with disease risk after we corrected for the
      number of genes analyzed. Thus, we could reject a model for the genetic
      architecture of type 2 diabetes where rare nonsynonymous variants clustered in a
      modest number of genes (fewer than 20) are responsible for the majority of
      disease risk. 

PMID- 24290380
TI  - Tumor burden in Hodgkin's lymphoma: much more than the best prognostic factor.
AB  - The intense immunological crosstalk between the rare neoplastic cells and the
      prevalent reactive ones is responsible for the development of signs and symptoms
      of Hodgkin's lymphoma. It is likely the reason for the superior predictivity
      constantly demonstrated by the tumor burden, as the final expression of the whole
      cytological disorder. Moreover, the tumor burden is related to the probability of
      response and its 1-year stability, showing different relationships according to
      the treatment administered. The relative risk of early treatment failure can be
      predicted on the basis of the tumor burden at diagnosis and the therapy chosen.
      Tumor burden is measured from the diagnostic whole body computed tomography (CT)
      scan, but can also be indirectly calculated from some staging parameters when the
      CT-aided assessment cannot be performed. Preliminary promising results have been
      obtained with a semi-automatic positron emission tomography/CT scan measuring
      metabolically active volumes, instead of whole visible masses. 

PMID- 24290381
TI  - Autism spectrum disorder and the cerebellum.
AB  - The cerebellum has been long known for its importance in motor learning and
      coordination. Recently, anatomical, clinical, and neuroimaging studies strongly
      suggest that the cerebellum supports cognitive functions, including language and
      executive functions, as well as affective regulation. Furthermore, the cerebellum
      has emerged as one of the key brain regions affected in autism. Here, we discuss
      our current understanding of the role of the cerebellum in autism, including
      evidence from genetic, molecular, clinical, behavioral, and neuroimaging studies.
      Cerebellar findings in autism suggest developmental differences at multiple
      levels of neural structure and function, indicating that the cerebellum is an
      important player in the complex neural underpinnings of autism spectrum disorder,
      with behavioral implications beyond the motor domain. 

PMID- 24290379
TI  - Recessive mutations in SLC38A8 cause foveal hypoplasia and optic nerve misrouting
      without albinism.
AB  - Foveal hypoplasia and optic nerve misrouting are developmental defects of the
      visual pathway and only co-occur in connection with albinism; to date, they have
      only been associated with defects in the melanin-biosynthesis pathway. Here, we
      report that these defects can occur independently of albinism in people with
      recessive mutations in the putative glutamine transporter gene SLC38A8. Nine
      different mutations were identified in seven Asian and European families. Using
      morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that
      pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an
      association study with SNPs at the SLC38A8 locus, we showed that common variants
      within this gene modestly affect foveal thickness in the general population. This
      study reveals a melanin-independent component underpinning the development of the
      visual pathway that requires a functional role for SLC38A8. 

PMID- 24290382
TI  - Contribution of long noncoding RNAs to autism spectrum disorder risk.
AB  - Accumulating evidence indicates that long noncoding RNAs (lncRNAs) contribute to
      autism spectrum disorder (ASD) risk. Although a few lncRNAs have long been
      recognized to have important functions, the vast majority of this class of
      molecules remains uncharacterized. Because lncRNAs are more abundant in human
      brain than protein-coding RNAs, it is likely that they contribute to brain
      disorders, including ASD. We review here the known functions of lncRNAs and the
      potential contributions of lncRNAs to ASD. 

PMID- 24290378
TI  - Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional
      variants differentially bind FOXA1 and E2F1.
AB  - The 10q26 locus in the second intron of FGFR2 is the locus most strongly
      associated with estrogen-receptor-positive breast cancer in genome-wide
      association studies. We conducted fine-scale mapping in case-control studies
      genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of
      European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry
      studies (n = 2,028) from the Breast Cancer Association Consortium. We identified
      three statistically independent risk signals within the locus. Within risk
      signals 1 and 3, genetic analysis identified five and two variants, respectively,
      highly correlated with the most strongly associated SNPs. By using a combination
      of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic
      mobility shift assays to study protein-DNA binding, we identified rs35054928,
      rs2981578, and rs45631563 as putative functional SNPs. Chromatin
      immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated
      allele (C) of rs2981578 and was able to recruit ERalpha to this site in an allele
      specific manner, whereas E2F1 preferentially bound the risk variant of
      rs35054928. The risk alleles were preferentially found in open chromatin and
      bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles
      are associated with changes in transcription. Chromatin conformation capture
      demonstrated that the risk region was able to interact with the promoter of
      FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating
      breast cancer susceptibility at this locus is consistent with the finding that
      the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease.

PMID- 24290384
TI  - Connecting signaling pathways underlying communication to ASD vulnerability.
AB  - Language is a human-specific trait that likely facilitated the rapid increase in
      higher cognitive function in our species. A consequence of the selective
      pressures that have permitted language and cognition to flourish in humans is the
      unique vulnerability of humans to developing cognitive disorders such as autism.
      Therefore, progress in understanding the genetic and molecular mechanisms of
      language evolution should provide insight into such disorders. Here, we discuss
      the few genes that have been identified in both autism-related pathways and
      language. We also detail the use of animal models to uncover the function of
      these genes at a mechanistic and circuit level. Finally, we present the use of
      comparative genomics to identify novel genes and gene networks involved in
      autism. Together, all of these approaches will allow for a broader and deeper
      view of the molecular brain mechanisms involved in the evolution of language and
      the gene disruptions associated with autism. 

PMID- 24290383
TI  - Identifying essential cell types and circuits in autism spectrum disorders.
AB  - Autism spectrum disorder (ASD) is highly genetic in its etiology, with
      potentially hundreds of genes contributing to risk. Despite this heterogeneity,
      these disparate genetic lesions may result in the disruption of a limited number
      of key cell types or circuits-information which could be leveraged for the design
      of therapeutic interventions. While hypotheses for cellular disruptions can be
      identified by postmortem anatomical analysis and expression studies of ASD risk
      genes, testing these hypotheses requires the use of animal models. In this
      review, we explore the existing evidence supporting the contribution of different
      cell types to ASD, specifically focusing on rodent studies disrupting
      serotonergic, GABAergic, cerebellar, and striatal cell types, with particular
      attention to studies of the sufficiency of specific cellular disruptions to
      generate ASD-related behavioral abnormalities. This evidence suggests multiple
      cellular routes can create features of the disorder, though it is currently
      unclear if these cell types converge on a final common circuit. We hope that in
      the future, systematic studies of cellular sufficiency and genetic interaction
      will help to classify patients into groups by type of cellular disruptions which
      suggest tractable therapeutic targets. 

PMID- 24290387
TI  - Motor skill in autism spectrum disorders: a subcortical view.
AB  - The earliest observable symptoms of autism spectrum disorders (ASDs) involve
      motor behavior. There is a growing awareness of the developmental importance of
      impaired motor function in ASD and its association with social skill. Compromised
      motor function requires increased attention, leaving fewer resources available
      for processing environmental stimuli and learning. This knowledge suggests that
      the motor system-which we know to be trainable-may be a gateway to improving
      outcomes of individuals living with ASD. In this review, we suggest a framework
      borrowed from machine learning to examine where, why, and how motor skills are
      different in individuals with ASD. 

PMID- 24290385
TI  - MET receptor tyrosine kinase as an autism genetic risk factor.
AB  - In this chapter, we will briefly discuss recent literature on the role of MET
      receptor tyrosine kinase (RTK) in brain development and how perturbation of MET
      signaling may alter normal neurodevelopmental outcomes. Recent human genetic
      studies have established MET as a risk factor for autism, and the molecular and
      cellular underpinnings of this genetic risk are only beginning to emerge from
      obscurity. Unlike many autism risk genes that encode synaptic proteins, the
      spatial and temporal expression pattern of MET RTK indicates this signaling
      system is ideally situated to regulate neuronal growth, functional maturation,
      and establishment of functional brain circuits, particularly in those brain
      structures involved in higher levels of cognition, social skills, and executive
      functions. 

PMID- 24290389
TI  - Immune dysregulation in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a highly heterogeneous disorder diagnosed based
      on the presence and severity of core abnormalities in social communication and
      repetitive behavior, yet several studies converge on immune dysregulation as a
      feature of ASD. Widespread alterations in immune molecules and responses are seen
      in the brains and periphery of ASD individuals, and early life immune disruptions
      are associated with ASD. This chapter discusses immune-related environmental and
      genetic risk factors for ASD, emphasizing population-wide studies and animal
      research that reveal potential mechanistic pathways involved in the development
      of ASD-related symptoms. It further reviews immunologic pathologies seen in ASD
      individuals and how such abnormalities can impact neurodevelopment and behavior.
      Finally, it evaluates emerging evidence for an immune contribution to the
      pathogenesis of ASD and a potential role for immunomodulatory effects in current
      treatments for ASD. 

PMID- 24290390
TI  - Autism susceptibility genes and the transcriptional landscape of the human brain.
AB  - Autism is the most severe end of a spectrum of neurodevelopmental conditions,
      autism spectrum disorders (ASD). ASD are genetically heterogeneous, and hundreds
      of genes have been implicated in the etiology of the disease. Here, we discuss
      the contribution of brain transcriptome studies in advancing our understanding of
      the genetic mechanisms of ASD and review recent work characterizing the spatial
      and temporal variation of the human brain transcriptome, with a focus on the
      relevance of these data to autism susceptibility genes. 

PMID- 24290386
TI  - Transcriptional dysregulation of neocortical circuit assembly in ASD.
AB  - Autism spectrum disorders (ASDs) impair social cognition and communication, key
      higher-order functions centered in the human neocortex. The assembly of
      neocortical circuitry is a precisely regulated developmental process susceptible
      to genetic alterations that can ultimately affect cognitive abilities. Because
      ASD is an early onset neurodevelopmental disorder that disrupts functions
      executed by the neocortex, miswiring of neocortical circuits has been
      hypothesized to be an underlying mechanism of ASD. This possibility is supported
      by emerging genetic findings and data from imaging studies. Recent research on
      neocortical development has identified transcription factors as key determinants
      of neocortical circuit assembly, mediating diverse processes including neuronal
      specification, migration, and wiring. Many of these TFs (TBR1, SOX5, FEZF2, and
      SATB2) have been implicated in ASD. Here, I will discuss the functional roles of
      these transcriptional programs in neocortical circuit development and their
      neurobiological implications for the emerging etiology of ASD.

PMID- 24290388
TI  - Orchestration of neurodevelopmental programs by RBFOX1: implications for autism
      spectrum disorder.
AB  - Neurodevelopmental and neuropsychiatric disorders result from complex
      interactions between critical genetic factors and as-yet-unknown environmental
      components. To gain clinical insight, it is critical to develop a comprehensive
      understanding of these genetic components. RBFOX1, an RNA splicing factor,
      regulates expression of large genetic networks during early neuronal development,
      and haploinsufficiency causes severe neurodevelopmental phenotypes including
      autism spectrum disorder (ASD), intellectual disability, and epilepsy. Genomic
      testing in individuals and large patient cohorts has identified phenotypically
      similar cases possessing copy number variations in RBFOX1, implicating the gene
      as an important cause of neurodevelopmental disease. However, a significant
      proportion of the observed structural variation is inherited from phenotypically
      normal individuals, raising questions regarding overall pathogenicity of
      variation at the RBFOX1 locus. In this chapter, we discuss the molecular,
      cellular, and clinical evidence supporting the role of RBFOX1 in neurodevelopment
      and present a comprehensive model for the contribution of structural variation in
      RBFOX1 to ASD. 

PMID- 24290391
TI  - Preface: the neurobiology of autism: integrating genetics, brain development,
      behavior, and the environment.

PMID- 24290392
TI  - Periviable birth: management and counseling issues--volume 1.

PMID- 24290393
TI  - Periviable births: epidemiology and obstetrical antecedents.
AB  - Confusion in terminology and non-standardized definitions can arguably be
      classified as the most important characteristics that lead to disparate study
      findings. While such situations abound in all of perinatal epidemiology, the
      study of "periviable birth" is a classic case in point. The most common term used
      to describe periviable birth has been extremely low birthweight (ELBW), often
      defined as newborns with birthweight below 1000g; yet, we identified 11 other
      descriptors for periviable birth. Due to the multitude of definitions, the
      reported incidence of periviable births varies from 0.03% to 1.9% (a relative
      difference of 7025%). Antecedent risk factors for periviable birth, though
      geographically heterogeneous, include nulliparity and multiple gestations, each
      accounting for one-third and one-fourth of all periviable births, respectively.
      Spontaneous preterm labor precedes 34% of these deliveries and premature rupture
      of membranes in 25%. The pregnancy was complicated by hypertensive disease in 21%
      and bleeding and chorioamnionitis in 18% each. Over 50% of these births are
      cesarean deliveries. Six clinical interventions before delivery that may improve
      outcomes include transfer of patient to a tertiary center, administration of
      antenatal corticosteroids, tocolytics, or antibiotics after premature rupture of
      membranes, assessment of fetal well-being with electronic fetal heart rate
      monitoring, and willingness to perform a cesarean delivery after the limit of
      viability is reached. While there is an accessible predictive model for mortality
      and long-term morbidities for newborns delivered at 22-25 weeks with weights of
      400-1000g, it is hampered by the need to know the birthweight. In addition to
      reaching a consensus regarding what birthweight-gestational age thresholds
      determine a periviable birth, the acute need to optimize neonatal outcomes
      remains a paramount target worthy of future research, and efforts to advance
      obstetrical medicine are needed to minimize the likelihood of its occurrence. 

PMID- 24290394
TI  - Survival of pre-viable preterm infants in the United States: a systematic review
      and meta-analysis.
AB  - The objective of this paper is to review observational studies that addressed the
      survival of pre-viable gestations in the United States. We searched PubMed, Ovid,
      CINAHL, and Web of Knowledge for studies reporting survival of infants born at
      <24 gestational weeks and/or <500g in the United States and published between
      January 2003 and January 2013. The full texts of 70 articles were examined and a
      total of 15 studies qualified and were selected. We analyzed fixed-effect and
      random-effects models for eight studies on survival to discharge. Pooled survival
      to discharge in the random-effects model was 45.9% (95% CI: 41.1-51.7) and 39.7%
      in the fixed-effect model (95% CI: 38.8-40.7). Studies differed by pre-viable
      survival measures and epochs (1985-2009). Protective factors included antenatal
      corticosteroids, neonatal resuscitation, and intensive care. The current survival
      threshold for pre-viable infants warrants reconsideration of the limits of
      viability. Protective factors that enhance survival should be considered in the
      management of these infants. 

PMID- 24290395
TI  - Fetal assessment near the limits of viability.
AB  - Assessments of gestational age are critical in dealing with the pregnancy at the
      limits of viability, 22-25-weeks gestation, where neonatal outcomes reveal very
      significant differences from week to week. The obstetrical team can estimate
      gestational age within a window of 7-10 days during this critical threshold at
      the window of viability via determination of last menstrual period, bimanual
      exam, early pregnancy test, and/or ultrasound. One must also take into account
      the impact of maternal disease processes, congenital abnormalities, number of
      fetus(es), and/or fetal growth restriction, along with ongoing evaluation and
      parental involvement in this decision-making process during the peri-viability
      period. 

PMID- 24290396
TI  - Prevention of periviable birth: bed rest, tocolysis, progesterone, and cerclage.
AB  - The periviable period is associated with a rapid improvement in both mortality
      and morbidity with increasing gestational age. Therapies that can prolong
      gestation have the potential for markedly improving outcome compared to later in
      pregnancy. The therapies commonly prescribed in order to prolong gestation
      include bed rest, tocolysis, progesterone, and cerclage. Although these therapies
      are used to prevent preterm birth throughout gestation, their impact on perinatal
      outcome during the periviable period remains largely unknown. These therapies are
      discussed relative to the periviable period exploring available data and possible
      impact on perinatal outcome. Studies specifically evaluating therapeutic
      interventions during the periviable period are lacking. 

PMID- 24290397
TI  - Antenatal corticosteroids for periviable birth.
AB  - Antenatal corticosteroids have been proven to accelerate fetal lung development
      and reduce neonatal morbidity and mortality when given between 28 and 34 weeks of
      gestation. However, there is only limited research to guide their use in the
      periviable period (22-26 weeks). Laboratory studies suggest that it is
      biologically plausible for antenatal steroids to be effective in this gestational
      period. In addition, cohort studies have demonstrated the efficacy of antenatal
      corticosteroids in reducing neonatal mortality and IVH. Follow-up studies
      performed between 18 and 22 months of age also suggest a long-term benefit to
      antenatal use in this period. Based on this information, antenatal
      corticosteroids should be used in appropriate patients at high risk for preterm
      birth at 23-26 weeks of gestation. An advantageous outcome to treatment at 22
      weeks is less certain. 

PMID- 24290398
TI  - Magnesium sulfate for cerebral palsy prevention.
AB  - Magnesium sulfate (MgSO4) has been shown to prevent cerebral palsy among children
      born to women at high risk of early preterm delivery. Three large, randomized
      placebo-controlled trials and a subsequent Cochrane Review suggest this
      intervention can decrease rates of cerebral palsy by 32% with a number needed to
      treat of 63 to prevent one case. Not only is MgSO4 familiar to obstetricians, it
      also has an excellent safety profile. Simple protocols exist to help guide
      clinicians in using MgSO4 for this indication. Evaluation of actual clinical
      practice shows that this use is both feasible and can be accomplished
      parsimoniously. 

PMID- 24290399
TI  - Mode of delivery for periviable birth.
AB  - The optimal mode of delivery when periviable birth is anticipated has been the
      subject of considerable discussion. Potentially, cesarean delivery could avert
      intrapartum fetal trauma and asphyxia and allow timed delivery to assure
      readiness of neonatal intensive care resources. However, cesarean delivery in the
      early preterm period commonly necessitates a classical vertical uterine incision
      involving the fundus with its associated acute and long-term risks to the mother
      and future pregnancies. In this study we evaluated the currently available
      literature regarding routine cesarean delivery, cesarean delivery for fetal
      malpresentation, and cesarean delivery for fetal indication near the limit of
      viability. Randomized controlled trials of adequate size regarding this issue are
      lacking. Data from retrospective and observational studies do not support routine
      cesarean delivery for all early preterm infants. Cesarean delivery may offer
      survival advantage to the periviable growth-restricted infant regardless of fetal
      presentation and appears to offer survival benefit to the malpresenting fetus. 

PMID- 24290400
TI  - Ethical issues in periviable birth.
AB  - Ethics is an essential dimension of the management of periviable birth in both
      clinical practice and research. The goal of clinical care in periviable birth is
      to improve outcomes for current pregnant and fetal patients. The goal of research
      in periviable birth is to improve outcomes for future pregnant patients and fetal
      patients. This paper provides an ethical framework for professionally responsible
      clinical management and research to improve the outcomes of periviable birth. The
      ethical framework is based on the professional responsibility model of obstetric
      ethics, which rejects rights-based reductionism. This model elaborates the
      ethical concept of the fetus as a patient in terms of beneficence-based and
      autonomy-based obligations to the pregnant woman and beneficence-based
      obligations to the fetus and emphasizes that the fetus is not a separate patient.
      Guidance is provided for counseling pregnant women about the management of
      pregnancies at 22 weeks of well-documented gestation, for which directive
      counseling in the form recommending non-aggressive obstetric management is
      ethically justified. At 24 weeks and later of gestation, directive counseling in
      the form of recommending aggressive obstetric management is ethically justified.
      For the period between 22 and 24 weeks gestation, non-directive counseling is
      ethically justified. Guidance is also provided for counseling pregnant women
      about participation in clinical trials and in innovative intervention for fetal
      benefit. Non-directive counseling should be strictly followed for both. 

PMID- 24290401
TI  - Periviable births: communication and counseling before delivery.
AB  - The potential delivery of an extremely premature infant presents a clinical
      situation that raises a complex combination of medical, social, ethical,
      religious, and economic issues. It is a unique medical encounter such that it is
      not all about "curing" the patient. Rather, it is an encounter where counseling
      is assisting families in deciding between life and death underscoring the
      stressful nature for both patients and providers. As with any other condition,
      health care providers are responsible for discussing all potential options and
      outcomes for families presented with the threat of an extremely premature infant.
      These decisions include but are not limited to place and mode of delivery,
      resuscitation decisions, and palliative management. Given the urgency of the
      situation, the emotionally charged nature of the decision, and the relative
      unpredictability prior to presentation, this particular situation poses unique
      challenges for all involved and mandates the need to have carefully constructed
      guidelines and processes for care and counseling that meet the needs of all
      involved. 

PMID- 24290402
TI  - Treatment of paracetamol overdose: room for improvement?

PMID- 24290403
TI  - Building clinical research capacity in China: the National Clinical Research
      Centres.

PMID- 24290405
TI  - Pelvic floor muscle training for pelvic organ prolapse.

PMID- 24290404
TI  - Individualised pelvic floor muscle training in women with pelvic organ prolapse
      (POPPY): a multicentre randomised controlled trial.
AB  - BACKGROUND: Pelvic organ prolapse is common and is strongly associated with
      childbirth and increasing age. Women with prolapse are often advised to do pelvic
      floor muscle exercises, but evidence supporting the benefits of such exercises is
      scarce. We aimed to establish the effectiveness of one-to-one individualised
      pelvic floor muscle training for reducing prolapse symptoms. METHODS: We did a
      parallel-group, multicentre, randomised controlled trial at 23 centres in the UK,
      one in New Zealand, and one in Australia, between June 22, 2007, and April 9,
      2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III
      prolapse were randomly assigned (1:1), by remote computer allocation with
      minimsation, to receive an individualised programme of pelvic floor muscle
      training or a prolapse lifestyle advice leaflet and no muscle training (control
      group). Outcome assessors, and investigators who were gynaecologists at trial
      sites, were masked to group allocation; the statistician was masked until after
      data analysis. Our primary endpoint was participants' self-report of prolapse
      symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is
      registered, number ISRCTN35911035. FINDINGS: 447 eligible patients were
      randomised to the intervention group (n=225) or the control group (n=222). 377
      (84%) participants completed follow-up for questionnaires at 6 months and 295
      (66%) for questionnaires at 12 months. Women in the intervention group reported
      fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic
      organ prolapse symptom score [POP-SS]) at 12 months than those in the control
      group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39];
      adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to
      missing data. Eight adverse events (six vaginal symptoms, one case of back pain,
      and one case of abdominal pain) and one unexpected serious adverse event, all in
      women from the intervention group, were regarded as unrelated to the intervention
      or to participation in the study. INTERPRETATION: One-to-one pelvic floor muscle
      training for prolapse is effective for improvement of prolapse symptoms. Long
      term benefits should be investigated, as should the effects in specific
      subgroups. FUNDING: Chief Scientist Office of the Scottish Government Health and
      Social Care Directorates, New Zealand Lottery Board, and National Health and
      Medical Research Council (Australia).

PMID- 24290407
TI  - Amino acid losses during sustained low efficiency dialysis in critically ill
      patients with acute kidney injury.
AB  - OBJECTIVE: Sustained low efficiency dialysis (SLED) involves the use of standard
      dialysis machines for prolonged intermittent renal replacement therapy in
      critically ill patients. In this study we aimed to quantify dialysate amino acid
      (AA) and albumin losses in 5 patients who underwent successful SLED treatment.
      DESIGN: This was a prospective observational study. SETTING: The study was
      performed in a general intensive care unit. SUBJECTS: The study was performed in
      critically ill patients with acute kidney injury undergoing SLED using low-flux
      hemodialyzers. INTERVENTION: We performed total dialysate collection and measured
      dialysate AA profiles by reverse phase high-pressure liquid chromatography using
      an automated AA analyser. MAIN OUTCOME MEASURE: Individual and total amino acid
      losses. RESULTS: Albumin was undetectable in dialysate. The median (mean +/- SD)
      total amino acid loss was 15.7 (23.4 +/- 19.2) g/treatment, or 122.1 (180.6 +/-
      148.5) mmol/treatment. Two patients were receiving intravenous nutrition. One
      patient had severe hepatic failure with encephalopathy, and had high dialysate AA
      levels with a total loss of 57 g/treatment. CONCLUSIONS: During SLED with low
      flux hemodialyzers, albumin losses are negligible but AA losses to dialysate are
      comparable to those during continuous renal replacement therapy. Patients'
      nutritional protein prescriptions should be augmented to account for this.

PMID- 24290408
TI  - Hemolytic uremic syndrome complicated with IgA nephropathy: a case report and
      literature review.
AB  - A previously healthy young female, presenting with nausea, vomiting, diarrhea,
      anemia, thrombocytopenia, and acute renal failure, was admitted to our hospital.
      Her clinical and histological features were consistent with both hemolytic uremic
      syndrome and IgA nephropathy, and she responded to steroid treatment, plasma
      transfusion, and gamma globulin therapy and did not need hemodialysis. In the
      following months, she achieved clinical remission except for low complement C3.
      Since hemolytic uremic syndrome is rarely associated with IgA nephropathy, we
      present this case and discuss potential connection between hemolytic uremic
      syndrome and IgA nephropathy. 

PMID- 24290409
TI  - Liposomal cisplatin can overcome chemotherapy resistance of A2780 ovarian cancer
      cells by inducing the extrinsic apoptotic pathway.

PMID- 24290406
TI  - Reduction of adverse effects from intravenous acetylcysteine treatment for
      paracetamol poisoning: a randomised controlled trial.
AB  - BACKGROUND: Paracetamol poisoning is common worldwide. It is treated with
      intravenous acetylcysteine, but the standard regimen is complex and associated
      with frequent adverse effects related to concentration, which can cause treatment
      interruption. We aimed to ascertain whether adverse effects could be reduced with
      either a shorter modified acetylcysteine schedule, antiemetic pretreatment, or
      both. METHODS: We undertook a double-blind, randomised factorial study at three
      UK hospitals, between Sept 6, 2010, and Dec 31, 2012. We randomly allocated
      patients with acute paracetamol overdose to either the standard intravenous
      acetylcysteine regimen (duration 20.25 h) or a shorter (12 h) modified protocol,
      with or without intravenous ondansetron pretreatment (4 mg). Masking was achieved
      by infusion of 5% dextrose (during acetylcysteine delivery) or saline (for
      antiemetic pretreatment). Randomisation was done via the internet and included a
      minimisation procedure by prognostic factors. The primary outcome was absence of
      vomiting, retching, or need for rescue antiemetic treatment at 2 h. Prespecified
      secondary outcomes included a greater than 50% increase in alanine
      aminotransferase activity over the admission value. Analysis was by intention to
      treat. This trial is registered with ClinicalTrials.gov (identifier NCT01050270).
      FINDINGS: Of 222 patients who underwent randomisation, 217 were assessable 2 h
      after the start of acetylcysteine treatment. Vomiting, retching, or need for
      rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to
      the shorter modified protocol compared with 71 of 109 allocated to the standard
      acetylcysteine regimen (adjusted odds ratio 0.26, 97.5% CI 0.13-0.52; p<0.0001),
      and in 45 of 109 patients who received ondansetron compared with 65 of 108
      allocated placebo (0.41, 0.20-0.80; p=0.003). Severe anaphylactoid reactions were
      recorded in five patients assigned to the shorter modified acetylcysteine regimen
      versus 31 who were allocated to the standard protocol (adjusted common odds ratio
      0.23, 97.5% CI 0.12-0.43; p<0.0001). The proportion of patients with a 50%
      increase in alanine aminotransferase activity did not differ between the standard
      (9/110) and shorter modified (13/112) regimens (adjusted odds ratio 0.60, 97.5%
      CI 0.20-1.83); however, the proportion was higher with ondansetron (16/111) than
      with placebo (6/111; 3.30, 1.01-10.72; p=0.024). INTERPRETATION: In patients with
      paracetamol poisoning, a 12 h modified acetylcysteine regimen resulted in less
      vomiting, fewer anaphylactoid reactions, and reduced need for treatment
      interruption. This study was not powered to detect non-inferiority of the shorter
      protocol versus the standard approach; therefore, further research is needed to
      confirm the efficacy of the 12 h modified acetylcysteine regimen. FUNDING: Chief
      Scientist Office of the Scottish Government.

PMID- 24290410
TI  - Pharmacokinetics of single-dose morinidazole in patients with severe renal
      impairment.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of morinidazole in individuals with
      severe renal impairment (RI). METHODS: This open-label Phase I study enrolled
      healthy volunteers and patients with severe RI aged 18 - 65 years. All subjects
      received a single infusion of sodium chloride injection with 500 mg morinidazole.
      Plasma and urine concentration of morinidazole and one of its metabolites (M4-1)
      were evaluated by using HPLC-UV and HPLC-MS/MS respectively. Pharmacokinetic
      parameters were calculated by Phoenix WinNonlin 6.0 software. RESULTS: 22
      individuals (healthy: n = 11, severe RI: n = 11) received morinidazole. In both
      groups, maximum plasma concentration of morinidazole was reached within 1 hour,
      while the tmax of M4-1 differed greatly. Both AUC0-t and AUC0-infinity of
      morinidazole were 1.4 times higher in patients with severe RI, while M4-1 were
      over 7 times higher than healthy groups. Renal excretion of unchanged
      morinidazole was decreased by 65% in patients with RI, and M4-1 was decreased by
      72%. Apparent correlation between CLcr and CL, AUC, t1/2 and CLr were seen in two
      groups. CONCLUSIONS: A single dose of 500 mg morinidazole is well tolerated.
      Changes in pharmacokinetic parameters of morinidazole and M4-1 are seen in
      patients with RI and may be clinically important.

PMID- 24290411
TI  - Two-way interaction study between ritonavir boosted danoprevir, a potent HCV
      protease inhibitor, and ketoconazole in healthy subjects.
AB  - BACKGROUND: Danoprevir is a potent, highly selective, macrocyclic, orally
      bioavailable inhibitor of the hepatitis C virus protease, and a substrate of
      cytochrome P450 (CYP) 3A. It is co-administered with low-dose ritonavir, a potent
      CYP3A inhibitor, to enhance danoprevir pharmacokinetics. Ketoconazole is a
      substrate for and potent selective inhibitor of CYP3A. METHODS: In this open
      label, 3-period study, the 2-way interaction potential between ritonavir-boosted
      danoprevir (danoprevir/r) and ketoconazole was investigated in 18 healthy
      subjects. Subjects initially received ketoconazole 200 mg q24h for 4 days (Period
      1) followed by a 7-day washout period. Danoprevir/r 100/100 mg q12h was then
      given for 10 days (Period 2) followed by a further 4 days of danoprevir/r 100/100
      mg q12h plus ketoconazole 200 mg q24h (Period 3). Serial blood samples were
      collected for the determination of danoprevir, ritonavir and/or ketoconazole
      plasma concentrations, and calculation of pharmacokinetic parameters. Safety and
      tolerability were monitored throughout the study. RESULTS: Co-administration of
      ketoconazole with danoprevir/r modestly increased the danoprevir AUCtau by 1.44
      fold, with no effect on danoprevir Cmax. Co-administration of danoprevir/r with
      ketoconazole substantially increased ketoconazole AUCtau and Cmax by 3.71-fold
      and 1.73-fold, respectively. Danoprevir/r was well tolerated when administered
      alone or with ketoconazole. CONCLUSIONS: These results indicate that the effect
      of potent CYP3A inhibitors, such as ketoconazole, on danoprevir/r
      pharmacokinetics is not likely to be clinically relevant.

PMID- 24290412
TI  - Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin
      hydroxy acid in healthy Chinese male and female volunteers.
AB  - BACKGROUND: Gender differences in pharmacokinetics have been reported to have
      important clinical consequences; however, no information about differences in the
      pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its
      metabolite, simvastatin hydroxy acid, in males and females is available.
      OBJECTIVE: The aim of this study was to investigate the effect of gender on the
      pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy
      Han Chinese volunteers. METHODS: 16 healthy volunteers (8 males and 8 females)
      were orally administered a single dose of 40 mg simvastatin lactone after an
      overnight fast. Plasma was then collected 24 hours after simvastatin lactone
      administration. Concentrations of simvastatin lactone and simvastatin hydroxy
      acid were measured by high performance liquid chromatography/mass
      spectrometry/mass spectrometry (HPLC/MS/MS). RESULTS: There were no significant
      associations between the pharmacokinetic parameters of simvastatin lactone and
      gender. For simvastatin hydroxy acid, peak plasma concentrations (Cmax) and dose
      normalized by the subject weight Cmax (NCmax) were higher in females than in
      males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC0
      24h, NAUC0-infinity) ratios of simvastatin hydroxy acid to simvastatin lactone in
      females were higher than in males. CONCLUSION: This study indicates that gender
      affects the plasma concentrations of active simvastatin hydroxy acid, but has no
      significant effect on parent simvastatin lactone. Raised plasma concentrations of
      simvastatin hydroxy acid in females may enhance the risk of systemic adverse
      effects during simvastatin lactone treatment.

PMID- 24290413
TI  - Pharmacokinetic properties and bioequivalence of olmesartan
      medoxomil/hydrochlorothiazide in healthy Korean male subjects.
AB  - Olmesartan medoxomil inhibits the vasoconstrictor effects of angiotensin II.
      Hydrochlorothiazide (HCTZ) promotes sodium excretion, resulting in a reduction of
      plasma volume and peripheral resistance. A combination of these agents is known
      to have a greater effect for the treatment of hypertension than monotherapy with
      either one of these components. OBJECTIVE: To assess bioequivalence between fixed
      dose combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) in
      healthy Korean subjects. METHODS: 40 healthy Korean volunteers were randomized
      into two groups. After administration of a single dose of investigational
      products, blood samples were collected before study drug administration
      (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours after
      study drug administration. The plasma concentrations of olmesartan and HCTZ were
      measured by LC-MS/MS. The pharmacokinetic parameters were calculated, and the 90%
      confidence intervals (CIs) of the geometric mean ratio (test/reference) of the
      parameters were obtained by analysis of variance (ANOVA) on logarithmically
      transformed data. RESULTS: The corresponding 90% CIs for the geometric mean ratio
      of the test to reference drugs were 0.93 - 1.04, 0.93 - 1.04, and 0.95 - 1.10.
      For HCTZ treatments, the 90% CIs for the geometric mean ratio of test to
      reference drugs were 0.95 - 1.03 for AUClast, 0.96 - 1.03 for AUCinfinity, and
      0.89 - 1.04 for Cmax. CONCLUSION: This study demonstrated that the test and
      reference products met the regulatory criteria assuming bioequivalence. Both
      formulations were safe and well tolerated, and there were no noteworthy
      differences in the safety profiles of the test and reference drugs.

PMID- 24290414
TI  - Pharmacokinetic comparison and bioequivalence evaluation of losartan/
      hydrochlorothiazide tablet between Asian Indian and Japanese volunteers.
AB  - OBJECTIVES: To demonstrate the bioequivalence between the test and reference
      formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablet and evaluate the
      effect of ethnicity on pharmacokinetics properties of losartan, losartan
      carboxylic acid and hydrochlorothiazide on healthy Asian Indian and Japanese
      volunteers. METHODS: Randomized, open-label, crossover, bioavailability studies
      were conducted separately in healthy Asian Indian and Japanese volunteers. One
      tablet either of test or of reference product was administered after 10 hours of
      overnight fasting. After dosing, serial blood samples were collected for a period
      of 48 hours for both the studies. Plasma samples were analyzed for losartan,
      losartan carboxylic acid and hydrochlorothiazide by a validated liquid
      chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic
      parameters AUC0-t, AUC0-infinity, Cmax, tmax, and other pharmacokinetics
      parameters were determined from plasma concentration-time profiles for both test
      and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablets.
      Statistical evaluations were done to evaluate bioequivalence between generic test
      formulation (EPR0001) and Japanese reference product (Preminent(r)). RESULTS:
      Losartan, losartan carboxylic acid and hydrochlorothiazide were well tolerated by
      subjects in all periods of each study under fasted conditions. No serious adverse
      events were observed. The ratios of least square means for AUC0-t and Cmax and
      the affiliated 90% confidence intervals were within acceptance range recommended
      by PMDA. Marginal differences were observed in pharmacokinetic values of Asian
      Indian and Japanese volunteers. CONCLUSIONS: The results of these bioavailability
      studies indicate that the test formulation of losartan/hydrochlorothiazide 50 +
      12.5 mg (EPR0001) tablets is bioequivalent to marketed Preminent(r) reference
      formulation in Asian Indian and Japanese volunteers, when administered under
      fasting conditions. Both test and reference formulations were well tolerated as a
      single oral dose when administered to healthy adult subjects under fasted
      conditions. Although Asian Indian and Japanese volunteers are ethnically
      different, results of these studies indicate that pharmacokinetic parameters of
      Asian Indian and Japanese volunteers are comparable to each other in terms of
      bioavailability of losartan, losartan carboxylic acid and hydrochlorothiazide.
      Similar least square means ratios were obtained in Asian Indian and Japanese
      volunteers demonstrating that a bioequivalence study conducted on Japanese
      volunteers seems to be substituted by Asian Indian volunteers' studies.

PMID- 24290416
TI  - Reply to: Clinical Neuropathology 2013; 32: 91-99. Spinal nerve root
      hemangioblastoma may be predominantly extradural.

PMID- 24290418
TI  - Volatile sulphur compounds in cheeses - an odorous analytical challenge.

PMID- 24290415
TI  - Pharmacokinetic comparisons between two formulations containing 100 mg of
      miglitol in healthy male Korean volunteers: a randomized, open-label, single
      dose, two-period, two-sequence crossover bioequivalence study.
AB  - BACKGROUND: Miglitol is an alpha-glucosidase inhibitor (AGI) used as an
      antihyperglycemic agent in the treatment of type 2 diabetes mellitus. The
      mechanism is that miglitol binds to and inhibits the alpha-glucosidase reversibly
      in the proximal intestine. Thus, carbohydrates not digested in the upper small
      intestine are transported to the lower intestine where they are eventually
      digested. OBJECTIVE: This study was performed for the subsequent marketing of the
      test miglitol formulation in Korea. We evaluated the comparative bioavailability
      and tolerability of the test and reference formulations in healthy male adult
      volunteers. METHODS: A total of 40 healthy adult subjects were enrolled in this
      single-dose, randomized, open-label, 2-period, 2-sequence, crossover
      bioequivalence study. During each period, subjects received 100 mg of miglitol
      test or reference. Blood samples from the subjects were obtained before dosing at
      0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, and 12 hours after oral drug administration.
      Plasma concentrations were determined by using liquid chromatography/mass
      spectrometry/mass spectrometry (LC-MS/MS). The PK parameters including AUCt,
      AUCinfinity, Cmax, and tmax were measured and all treatment-emergent adverse
      events (TEAEs) and their relationships to study these medications were recorded
      throughout the entire study. RESULTS: A total of 40 healthy adult male Korean
      subjects were enrolled in the study and randomized into two treatment groups.
      Ultimately, 33 subjects completed the study. During each treatment period, blood
      samples were collected at specific time intervals from 0 to 12 hours after
      administration of a single drug dose. The PK parameters including AUCt,
      AUCinfinity, Cmax, and tmax were calculated and the 90% CIs of the ratio
      (test/reference) of the parameters were obtained by analysis of variance (ANOVA)
      on logarithmically transformed data. The 90% CIs of the geometric mean ratios for
      the test to reference formulations were as follows: 1.05 (0.97 - 1.13) for AUCt
      and 1.05 (0.96 - 1.14) for Cmax. Statistical analysis confirmed that the 90% CIs
      for these PK parameters were within the commonly accepted bioequivalence range of
      0.8 - 1.25. There were no serious or unexpected TEAEs during the study.
      CONCLUSIONS: In the healthy adult Korean subjects, the test and reference
      formulations had similar PK parameters and similar plasma concentration-time
      profiles. The test formulation of miglitol met the Korean regulatory criteria
      (AUCt and Cmax) for assuming bioequivalence and both formulations were generally
      well-tolerated. The CRiS identifiers: KCT0000770.

PMID- 24290419
TI  - Energy-related chemical research at the Universities of Applied Sciences.
AB  - An overview of current activities in the field of energy-related chemical
      research at the Swiss Universities of Applied Sciences is presented. 

PMID- 24290422
TI  - Salutogenically focused outcomes in systematic reviews of intrapartum
      interventions: a systematic review of systematic reviews.
AB  - INTRODUCTION: research on intrapartum interventions in maternity care has focused
      traditionally on the identification of risk factors' and on the reduction of
      adverse outcomes with less attention given to the measurement of factors that
      contribute to well-being and positive health outcomes. We conducted a systematic
      review of reviews to determine the type and number of salutogenically-focused
      reported outcomes in current maternity care intrapartum intervention-based
      research. For the conduct of this review, we interpreted salutogenic outcomes as
      those relating to optimum and/or positive maternal and neonatal health and well
      being. OBJECTIVES: to identify salutogenically-focused outcomes reported in
      systematic reviews of randomised trials of intrapartum interventions. REVIEW
      METHODS: we searched Issue 9 (September) 2011 of the Cochrane Database of
      Systematic Reviews for all reviews of intrapartum interventions published by the
      Cochrane Pregnancy and Childbirth Group using the group filter "hm-preg".
      Systematic reviews of randomised trials of intrapartum interventions were
      eligible for inclusion. We excluded protocols for systematic reviews and
      systematic reviews that had been withdrawn. Outcome data were extracted
      independently from each included review by at least two review authors. Unique
      lists of salutogenically and non-salutogenically focused outcomes were
      established. RESULTS: 16 salutogenically-focused outcome categories were
      identified in 102 included reviews. Maternal satisfaction and breast feeding were
      reported most frequently. 49 non-salutogenically-focused outcome categories were
      identified in the 102 included reviews. Measures of neonatal morbidity were
      reported most frequently. CONCLUSION: there is an absence of salutogenically
      focused outcomes reported in intrapartum intervention-based research. We
      recommend the development of a core outcome data set of salutogenically-focused
      outcomes for intrapartum research.

PMID- 24290423
TI  - The experience of pregnant women with a diagnosis of fetal lower urinary tract
      obstruction (LUTO).
AB  - OBJECTIVE: to gain insight into the experiences and perspectives of pregnant
      women diagnosed antenatally with fetal lower urinary tract obstruction (LUTO)
      participating in an interventional fetal medicine randomised controlled trial
      (RCT). DESIGN: a qualitative study using semi-structured interviews. Interviews
      were analysed using Riessman's narrative analysis. SETTING: fetal medicine
      clinics within the United Kingdom National Health Service (NHS). PARTICIPANTS:
      five pregnant women who were recruited as part of an RCT and two additional women
      who were recruited after the trial was terminated before completion. FINDINGS:
      three themes were identified and form the basis of this article: the use of
      technology in pregnancy, the loss of a normal pregnancy, and decision making in
      uncertainty. IMPLICATIONS AND CONCLUSIONS: undertaking qualitative research
      within an RCT can illuminate the experience of the condition being studied.
      Women's experience of a pregnancy where LUTO was diagnosed in the fetus entailed
      an emotional journey following the visualisation of the abnormality through the
      use of routine ultrasound screening. Women tried to make sense of the diagnosis
      in order to make the best, albeit less than ideal, decisions for themselves,
      their baby, and their family. Midwives are in a good position to support women
      through the emotional distress of diagnosis and to help them negotiate the
      uncertain terrain in which they make decisions.

PMID- 24290424
TI  - The utilization of poisons information resources in Australasia.
AB  - PURPOSE: To identify poisons information resources most commonly utilized by
      Australasian Emergency Department staff, and examine attitudes regarding the
      benefits and user experience of the electronic products used. METHODS: A survey
      tool was mailed to six Emergency Departments each in New Zealand and Australia to
      be answered by medical and nursing staff. RESULTS: Eighty six (71.7%) responses
      were received from the 120 survey forms sent: 70 (81%) responders were medical
      staff, the remainder nursing. Electronic resources were the most accessed poisons
      information resource in New Zealand; Australians preferring discussion with a
      colleague; Poisons Information Centers were the least utilized resource in both
      countries. With regard to electronic resources, further differences were
      recognized between countries in: ease of access, ease of use, quality of
      information and quantity of information, with New Zealand better in all four
      themes. CONCLUSIONS: New Zealand ED staff favored electronic poisons information
      resources while Australians preferred discussion with a colleague. That Poisons
      Information Centers were the least utilized resource was surprising.

PMID- 24290425
TI  - A passionate endurance cyclist ultimately survives sudden death in right
      ventricular giant cell myocarditis.

PMID- 24290427
TI  - Can we further examine patients without perfusion imaging?

PMID- 24290426
TI  - Hyperuricemia and the risk of ischemic stroke in patients with atrial
      fibrillation--could it refine clinical risk stratification in AF?
AB  - BACKGROUND: Although hyperuricemia has been reported to be a risk factor of
      stroke, the relationship between hyperuricemia and stroke in patients with atrial
      fibrillation (AF) remains uncertain. The goal of the present study was to
      investigate whether hyperuricemia could potentially refine clinical risk
      stratification in AF. METHODS: This study used the "National Health Insurance
      Research Database" in Taiwan. A total of 7601 AF patients who did not receive
      antiplatelet agents or oral anticoagulants were identified as the study
      population. Hyperuricemia was defined as having at least one episode of gout
      attack necessitating long-term treatment with uric acid-lowering agents. The
      association between hyperuricemia and ischemic stroke was analyzed. RESULTS:
      During the follow up of 3.0+/-2.7 years, 1116 patients (14.7%) experienced
      ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly
      predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2
      VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc
      score of 0, hyperuricemia can further stratify them into 2 groups with different
      stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in
      predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc
      score of 0 to 1.659 for those with a score of 3, and became insignificant for
      patients with a score >=4. CONCLUSIONS: Hyperuricemia was a significant risk
      factor of stroke which could potentially refine the clinical risk stratification
      in AF. It deserves a prospective trial to investigate whether it would change the
      current strategy for stroke preventions using oral anticoagulants.

PMID- 24290428
TI  - Applying chemical bile duct embolization to achieve chemical hepatectomy in
      hepatolithiasis: a further experimental study.
AB  - BACKGROUND: Hepatolithiasis is the presence of calculi within the bile ducts of
      the liver. It represents a significant problem for hepatobiliary surgery because
      of its high recurrence rate and the associated risk for partial hepatectomy. This
      study was designed to explore the long-term efficacy of chemical biliary duct
      embolization (CBDE) to treat recurrent hepatolithiasis. MATERIALS AND METHODS: A
      rabbit model of hepatolithiasis was established, and CBDE was achieved using
      oxybenzene and N-butyl-cyanoacrylate. The short-term (6 wk) and long-term (12 wk)
      efficacy of CBDE treatment was compared by observing the degree of atrophy,
      fibrosis, proliferation of collagen fibers, and apoptosis of hepatocytes and
      hepatic stellate cells in the embolized hepatic lobe. Biochemical measurement of
      beta-glucuronidase was also evaluated to determine the effect of CBDE on stone
      formation. RESULTS: Six weeks after CBDE, there was liver cell destruction,
      collagen accumulation, and bile duct proliferation only in the peripheral part of
      the target lobe. Twelve weeks after CBDE, "self-cut" chemical hepatectomy was
      achieved, as manifested by the destruction of almost all the hepatocytes in the
      target lobe, bile duct proliferation, and collagen fiber accumulation. The beta
      glucuronidase activity was markedly lower in the embolized lobe than in the
      nonembolized lobe. In contrast, bax, caspase-3, caspase-9, and alpha-smooth
      muscle actin expression was substantially higher in the embolized lobe than in
      the sham-operation group at 6 wk, but was lower at 12 wk. CONCLUSIONS: CBDE is a
      potentially effective therapeutic approach for treating and preventing the
      recurrence of hepatolithiasis.

PMID- 24290429
TI  - Radiofrequency-assisted versus clamp-crush liver resection: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Conflicting results were found between radiofrequency-assisted liver
      resection (RF-LR) and clamp-crush liver resection (CC-LR) during liver surgery.
      We conducted a systematic review and meta-analysis that included randomized
      controlled trials (RCTs) and non-RCTs to compare the effectiveness and safety of
      RF-LR versus CC-LR during liver surgery. METHODS: Articles comparing RF-LR and CC
      LR that were published before December 2012 were retrieved and subjected to a
      systematic review and meta-analysis. Data synthesis and statistical analysis were
      carried out by Review Manager Version 5.2 software. RESULTS: In all, four RCTs
      and five nonrandomized studies evaluating 728 patients were included. Compared
      with CC-LR, the RF-LR group had significantly reduced total intraoperative blood
      loss (weighted mean difference [WMD] = -187 mL; 95% confidence interval [CI] = 
      312, -62; data on 628 patients), and blood loss during liver transection (WMD = 
      143.7 mL; 95% CI = -200, -87; data on 190 patients). However, RF-LR is associated
      with a higher rate of intra-abdominal abscess than the clamp-crushing method
      (odds ratio = 3.61; 95% CI = 1.26, 10.32; data on 366 patients). No significant
      difference was observed between both the groups for the incidence of both blood
      transfusion and bile leak. CONCLUSIONS: There is currently not sufficient
      evidence to support or refute the use of RF-LR in liver surgery. RF-LR has
      advantages in terms of reducing blood loss. However, RF-LR may increase the rates
      of both bile leak and abdominal abscess. So, the safety of RF-LR has not been
      established. Future well-designed RCTs are awaited to further investigate the
      efficacy and safety of RF devices in liver resection.

PMID- 24290430
TI  - Inhibition of histone deacetylases protects septic mice from lung and splenic
      apoptosis.
AB  - BACKGROUND: Epigenetic programming, dynamically regulated by histone acetylation,
      may play a key role in the pathophysiology of sepsis. We examined whether histone
      deacetylase (HDAC) can contribute to sepsis-associated inflammation and
      apoptosis. MATERIALS AND METHODS: Polymicrobial sepsis was induced by cecal
      ligation and puncture (CLP) in BALB/c mice. An intraperitoneal injection of
      CG200745 (10 mg/kg), a novel broad-spectrum HDAC inhibitor, or valproic acid (500
      mg/kg), a predominant inhibitor of class I HDACs, was given 3 h before surgery.
      RESULTS: HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after
      CLP. Furthermore, CLP-induced sepsis increased both histone H3 and H4 acetylation
      levels in lungs. When CG200745 was given, apoptosis induction was strongly
      suppressed in lungs and spleens of septic mice. This antiapoptotic effect of
      CG200745 was not accompanied by upregulation of antiapoptotic and downregulation
      of proapoptotic Bcl-2 family member proteins. Treatment with CG200745 failed to
      inhibit elevated levels of serum cytokines and prevent lung inflammation in
      septic mice. Valproic acid also showed antiapoptotic but not anti-inflammatory
      effects in septic mice. CONCLUSIONS: These findings imply that HDAC inhibitors
      are a unique agent to prevent cell apoptosis in sepsis at their doses that do not
      improve inflammatory features, indicating that septic inflammation and apoptosis
      may not necessarily be essential for one another's existence. This study also
      represents the first report that CLP-induced sepsis downregulates HDACs.
      Nevertheless, the data with HDAC inhibitors suggest that imbalance in histone
      acetylation may play a contributory role in expression or repression of genes
      involved in septic cell apoptosis.

PMID- 24290432
TI  - Compartment syndrome after gynecologic operations: evidence from case reports and
      reviews.
AB  - Compartment syndrome (CS) of the lower leg is a rare but severe complication of
      operations in the lithotomy (LT) position after urologic, gynecologic and general
      surgery. A delay in diagnosis and treatment can lead to loss of function and even
      life-threatening complications. The pathophysiology is still not fully understood
      but it is believed that ischemia as a result of increased compartment pressure
      and decreased perfusion pressure may lead to CS. The type of leg support and the
      intraoperative hypotension have been discussed as risk factors but evidence is
      mainly based on case reports and expert opinion. Studies suggest that time spent
      in the LT position and the addition of head-down tilt are associated with CS. As
      these positions are routinely applied during various gynecologic procedures,
      forensically CS has to be considered as a specific complication of gynecologic
      surgery in the LT position. Despite the low incidence there is a need for
      prospective studies and guidelines for its prevention. Sixteen case reports
      describing 19 cases of CS following gynecologic surgery in lithotomy position
      were found during a literature search. This review is based on 14 of these case
      reports (17 cases), which describe a postoperative compartment syndrome in a
      previously healthy leg. We summarize the reported cases and literature on CS
      after gynecologic procedures in order to increase awareness among medical staff
      and to give careful recommendations regarding perioperative management based on
      available information. 

PMID- 24290433
TI  - Medial hip arthroscopy portals: an anatomic study.
AB  - PURPOSE: The main objective of this study was to investigate medial hip portals
      and evaluate their relation with anatomic structures in a cadaveric model.
      METHODS: Placement of 3 medial arthroscopic portals was simulated in 10 fresh
      human paired cadaveric hip specimens by placing Steinmann pins into the joint
      under fluoroscopic control. Two portals were made at the groin, 1 anterior and 1
      posterior to the adductor longus muscle, and the third portal was placed
      posterior to the adductor longus muscle, 5 cm distal to the groin. The specimens
      were then dissected, and the relation of the portals to the following structures
      was recorded: pectineus, adductor longus, gracilis, adductor brevis, adductor
      magnus, iliopsoas tendon, obturator nerve, femoral nerve, femoral artery, femoral
      vein, and profunda femoris artery. RESULTS: Regarding the anteromedial portal,
      the closest neurovascular structure was the profunda femoris artery, which was
      10.4 +/- 2.7 mm (range, 6 to 14 mm) distal to the portal. Regarding the
      posteromedial portal, the nearest neurovascular structure was the obturator
      nerve, which was 6.0 +/- 3.6 mm (range, 2 to 13 mm) posterior to the portal.
      Regarding the distal posteromedial portal, the nearest neurovascular structures
      were the obturator nerve, which was 4.6 +/- 3.0 mm (range, 1 to 9 mm) distal to
      the portal, and the profunda femoris artery, which was 10.5 +/- 3.9 mm (range, 6
      to 17 mm) distal to the portal. CONCLUSIONS: The use of the medial portals did
      not cause any damage to the neurovascular structures evaluated. Despite this, the
      portals are in close relation to the obturator nerve and profunda femoris, and
      care should be taken. CLINICAL RELEVANCE: This study investigated 3 medial hip
      portals in a cadaveric model and also defined safety parameters for this
      approach. Medial hip portals may be useful to directly approach medial hip
      pathologies.

PMID- 24290434
TI  - Chronic inflammatory state in sickle cell anemia patients is associated with
      HBB(*)S haplotype.
AB  - The chronic inflammatory state in sickle cell anemia (SCA) is associated with
      several factors such as the following: endothelial damage; increased production
      of reactive oxygen species; hemolysis; increased expression of adhesion molecules
      by leukocytes, erythrocytes, and platelets; and increased production of
      proinflammatory cytokines. Genetic characteristics affecting the clinical
      severity of SCA include variations in the hemoglobin F (HbF) level, coexistence
      of alpha-thalassemia, and the haplotype associated with the HbS gene. The
      different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian.
      These haplotypes are associated with ethnic groups and also based on the
      geographical origin. Studies have shown that the Bantu haplotype is associated
      with higher incidence of clinical complications than the other haplotypes and is
      therefore considered to have the worst prognosis. This study aimed to evaluate
      the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor
      alpha, and interleukin-17 in patients with SCA and also to assess the haplotypes
      associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62
      patients who had SCA and had been treated with hydroxyurea; they had received a
      dose ranging between 15 and 25 (20.0+/-0.6)mg/kg/day for 6-60 (18+/-3.4)months;
      their data were compared with those for 30 normal individuals. The presence of
      HbS was detected and the haplotypes of the beta S gene cluster were analyzed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      Our study demonstrated that SCA patients have increased inflammatory profile when
      compared to the healthy individuals. Further, analysis of the association between
      the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF
      alpha were greater in subjects with the Bantu/Bantu haplotype than in subjects
      with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower
      levels of cytokines than those with the Bantu/Bantu haplotype and greater levels
      than those of subjects with the Benin/Benin haplotype. For IL-17, a slight trend
      toward decreased levels was observed in the subjects with the Benin/Benin
      haplotype, when compared to those with the Bantu/Bantu and Bantu/Benin
      haplotypes; however, this difference was not statistically significant. Our
      results show that genetic polymorphisms in sickle cell anemia are associated with
      the inflammatory profile. 

PMID- 24290435
TI  - The association of IL-8-251T/A polymorphism with complicated malaria in Karbi
      Anglong district of Assam.
AB  - Amongst host genetic factors, cytokine gene polymorphism can be anticipated to be
      an important factor as qualitative, quantitative and time of secretion play an
      important role in disease outcome. We have investigated association of cytokine
      promoter SNPs with risk of Plasmodium falciparum malaria and disease severity in
      a case control study in malaria endemic Karbi Anglong district of Assam, India.
      Frequency of IL-8-251T/A (p=0.03 and p=0.01) and TGF-beta1-509C/T (p=0.02 and
      p=0.03) was higher in malaria in comparison to control participants and non
      malarial fever controls. Interestingly, a higher frequency of mutant allele of IL
      10-819T/C was observed in non-malarial fever controls compared to malaria thus
      suggesting its role as a distinguishing marker of the two disease groups. Higher
      IL-8 expression and increased frequency of IL-8-251T/A in complicated malaria
      (p=0.002) was reported indicating its role in susceptibility to complicated
      malaria. In conclusion, our study suggests the role of mutant genotype of IL-8
      251T/A as a marker of complicated malaria in our population. Surprisingly,
      decreased expression of TGF-beta1 in uncomplicated malaria even in presence of
      high expressing mutant genotype was observed and needs to be investigated in
      context of the pool of activated cells producing the cytokine. 

PMID- 24290436
TI  - Evaluation of the kinetic oxidation of aqueous volatile organic compounds by
      permanganate.
AB  - The use of permanganate solutions for in-situ chemical oxidation (ISCO) is a well
      established groundwater remediation technology, particularly for targeting
      chlorinated ethenes. The kinetics of oxidation reactions is an important ISCO
      remediation design aspect that affects the efficiency and oxidant persistence.
      The overall rate of the ISCO reaction between oxidant and contaminant is
      typically described using a second-order kinetic model while the second-order
      rate constant is determined experimentally by means of a pseudo first order
      approach. However, earlier studies of chlorinated hydrocarbons have yielded a
      wide range of values for the second-order rate constants. Also, there is limited
      insight in the kinetics of permanganate reactions with fuel-derived groundwater
      contaminants such as toluene and ethanol. In this study, batch experiments were
      carried out to investigate and compare the oxidation kinetics of aqueous
      trichloroethylene (TCE), ethanol, and toluene in an aqueous potassium
      permanganate solution. The overall second-order rate constants were determined
      directly by fitting a second-order model to the data, instead of typically using
      the pseudo-first-order approach. The second-order reaction rate constants (M(-1)
      s(-1)) for TCE, toluene, and ethanol were 8.0*10(-1), 2.5*10(-4), and 6.5*10(-4),
      respectively. Results showed that the inappropriate use of the pseudo-first-order
      approach in several previous studies produced biased estimates of the second
      order rate constants. In our study, this error was expressed as a function of the
      extent (P/N) in which the reactant concentrations deviated from the
      stoichiometric ratio of each oxidation reaction. The error associated with the
      inappropriate use of the pseudo-first-order approach is negatively correlated
      with the P/N ratio and reached up to 25% of the estimated second-order rate
      constant in some previous studies of TCE oxidation. Based on our results, a
      similar relation is valid for the other volatile organic compounds studied.

PMID- 24290437
TI  - Enantiomer profiling of high loads of amphetamine and MDMA in communal sewage: a
      Dutch perspective.
AB  - Analysis of wastewater with an aim of community-wide estimation of drug use is a
      new and very promising approach. Until now it was very difficult to determine if
      mass loads of studied drugs were actually originating from consumption, or
      disposal of unused drugs or production waste. This uncertainty in the estimation
      of community wide drugs use should not be underestimated. This paper aims to
      apply for the first time enantiomeric profiling in verifying sources of the
      presence of MDMA and amphetamine in wastewater based on a case study in two Dutch
      cities: Utrecht and Eindhoven. The results showed that MDMA is usually present in
      wastewater due to its consumption (MDMA enriched with R(-)-enantiomer).
      Excessively high mass loads of MDMA during a sampling campaign in Utrecht in 2011
      proved to be racemic indicating direct disposal of unused MDMA possibly as a
      result of a police raid at a nearby illegal production facility. Enantiomeric
      profiling was also undertaken in order to verify the origin of unexpectedly high
      mass loads of amphetamine in the city of Eindhoven in 2011. Unfortunately, a
      distinction between consumption and direct disposal of unused amphetamine in
      Dutch wastewater could not be achieved. Further work will have to be undertaken
      to fully understand sources of amphetamine in Dutch wastewaters. 

PMID- 24290431
TI  - Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis
      and assessment of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that
      affects up to 25% of children and 2% to 3% of adults. This guideline addresses
      important clinical questions that arise in the management and care of AD,
      providing updated and expanded recommendations based on the available evidence.
      In this first of 4 sections, methods for the diagnosis and monitoring of disease,
      outcomes measures for assessment, and common clinical associations that affect
      patients with AD are discussed. Known risk factors for the development of disease
      are also reviewed. 

PMID- 24290438
TI  - Arsenic mitigation in Bangladesh: an analysis of institutional stakeholders'
      opinions.
AB  - While Bangladesh made significant achievements in safe water coverage via
      installation of shallow tubewells (STWs) nationwide, this success was shattered
      by the discovery of arsenic (As) in the STWs. The extent and severity of As
      groundwater contamination throughout Bangladesh and its detrimental effects on
      human health are well known and demand long-term sustainable mitigation. It is an
      immensely complex and expensive task to bring tens of millions of arsenic exposed
      people under safe water coverage. While various mitigation measures have been
      undertaken by various organizations, most have not achieved their expected
      outcomes due to technical, spatial and socio-economic challenges. Better
      understanding of these challenges by institutional stakeholders is crucial for
      sustainable arsenic mitigation in Bangladesh. In this study, institutional
      stakeholders' opinions on various aspects of As mitigation were elicited to
      identify their preferences for and reservations of specific mitigation measures.
      The current status of As mitigation activities and the factors influencing the
      success of As mitigation were also explored. Institutional weakness, lack of
      accountability and a latency period were the major factors hindering sustainable
      As mitigation. The results also suggested that the stakeholders' understanding of
      the As problem and their preferences for the different mitigation measures have a
      significant impact on the effectiveness of As mitigation. Mitigation of As
      contamination is a complex issue that requires a coordinated effort from various
      levels of stakeholders. The concept of "paying for water", which is currently
      potentially unknown in the rural areas of Bangladesh, also needs to be developed
      as this will create a stronger sense of user ownership of As safe water and thus
      better water management. 

PMID- 24290439
TI  - A 3D Alzheimer's disease culture model and the induction of P21-activated kinase
      mediated sensing in iPSC derived neurons.
AB  - The recent progress in stem cell techniques has broadened the horizon for in
      vitro disease modeling. For desired in vivo like phenotypes, not only correct
      cell type specification will be critical, the microenvironmental context will be
      essential to achieve relevant responses. We demonstrate how a three dimensional
      (3D) culture of stem cell derived neurons can induce in vivo like responses
      related to Alzheimer's disease, not recapitulated with conventional 2D cultures.
      To acquire a neural population of cells we differentiated neurons from
      neuroepithelial stem cells, derived from induced pluripotent stem cells. p21
      activated kinase mediated sensing of Abeta oligomers was only possible in the 3D
      environment. Further, the 3D phenotype showed clear effects on F-actin associated
      proteins, connected to the disease processes. We propose that the 3D in vitro
      model has higher resemblance to the AD pathology than conventional 2D cultures
      and could be used in further studies of the disease.

PMID- 24290440
TI  - Chondroitin sulphate-based 3D scaffolds containing MWCNTs for nervous tissue
      repair.
AB  - Nervous tissue lesions are an important social concern due to their increasing
      prevalence and their high sanitary costs. Their treatment still remains a
      challenge because of the reduced ability of nervous tissue to regenerate, its
      intrinsic structural and functional complexity and the rapid formation of
      fibroglial scars inhibiting neural repair. Herein, we show that 3D porous
      scaffolds made of chondroitin sulphate (CS), a major regulatory component of the
      nervous tissue, and multi-walled carbon nanotubes (MWCNTs) are selective
      substrates for the formation of a viable and neuron-enriched network with a
      transitory low glial content. Scaffolds have been fabricated by using the ice
      segregation-induced self-assembly technique and cultured with embryonic neural
      progenitor cells. Cell adhesion, morphology, viability, neuron/glial
      differentiation, calcium signaling dynamics, and mitochondrial activity have been
      studied over time on the scaffolds and compared to appropriate 2D control
      substrates. Our results indicate the formation of viable cultures enriched in
      neuron cells for up to 20 days, with ability to display calcium transients and
      active mitochondria, even in the absence of poly-D-lysine coating. A synergistic
      neural-permissive signaling from both the scaffold structure and its components
      (i.e., MWCNTs and CS) is suggested as the major responsible factor for these
      findings. We anticipate that these scaffolds may serve nerve regeneration if
      implanted in the acute phase after injury, as it is during the first stages of
      graft implantation when the most critical sequence of phenomena takes place to
      drive either nervous regeneration or fibroglial scar formation. The temporary
      glial inhibition found may be, indeed, beneficial for promoting the formation of
      neuron-enriched circuits at early phases while guaranteeing posterior glial
      integration to support longer-term neuron survival and activity.

PMID- 24290441
TI  - The inhibition of migration and invasion of cancer cells by graphene via the
      impairment of mitochondrial respiration.
AB  - Graphene and its derivatives have become important nanomaterials worldwide and
      have potential medical applications including in vivo diagnosis, drug delivery,
      and photothermal therapy of cancer. However, little is known about their effect
      on the metastasis of cancer cells, which is the cause of over 90% of patient
      deaths. In the present investigation, we provide direct evidence that low
      concentrations of pristine graphene and graphene oxide show no apparent influence
      on the viability of MDA-MB-231 human breast cancer cells, PC3 human prostate
      cancer cells, as well as B16F10 mouse melanoma cells. However, both pristine
      graphene and graphene oxide can effectively inhibit the migration and invasion of
      these cancer cells. Further studies indicate that exposure of cells to graphene
      led to the direct inhibition of the electron transfer chain complexes I, II, III
      and IV, most likely by disrupting electron transfer between iron-sulfur centers,
      which is due to its stronger ability to accept electrons compared to iron-sulfur
      clusters through theoretical calculations. The decreased electron transfer chain
      activity caused a reduction in the production of ATP and subsequent impairment of
      F-actin cytoskeleton assembly, which is crucial for the migration and invasion of
      metastatic cancer cells. The inhibition of cancer cell metastasis by graphene and
      graphene oxide might provide new insights into specific cancer treatment.

PMID- 24290443
TI  - Changes in opioid prescribing for Washington workers' compensation claimants
      after implementation of an opioid dosing guideline for chronic noncancer pain:
      2004 to 2010.
AB  - An opioid overdose epidemic emerged in the United States following increased
      opioid prescribing for chronic noncancer pain. In 2007, Washington State agencies
      implemented an opioid dosing guideline on safe prescribing for chronic noncancer
      pain. The objective of this population-based observational study was to evaluate
      opioid use and dosing before and after guideline implementation. We identified
      161,283 workers aged 18 to 64 years with >=1 opioid prescriptions in Washington
      Workers' Compensation, April 1, 2004, to December 31, 2010. Prevalence and
      incidence rates of opioid use were assessed. We compared pre- and postguideline
      chronic and high-dose use (>=120 mg/d) among incident users. The mean monthly
      prevalence of opioid use declined by 25.6% between 2004 (14.4%) and 2010 (10.7%).
      Fewer incident users went on to chronic opioid therapy in the postguideline
      period (4.7%; 95% confidence interval [CI], 4.5-5.0%) than in the preguideline
      period (6.3%; 95% CI, 6.1-6.6%). Compared with preguideline incident users,
      postguideline incident users were 35% less likely to receive high doses (adjusted
      odds ratio = .65; 95% CI, .59-.71). Although the extent to which decreases were
      due to the guidelines is uncertain, to our knowledge, this is the first report of
      significant decreases in chronic and high-dose prescription opioid use among
      incident users. PERSPECTIVE: Evidence-based strategies for opioid risk management
      are needed to help abate the epidemic of opioid-related morbidity and mortality.
      The study findings suggest that opioid dosing guidelines that specify a "yellow
      flag" dosing threshold may be a useful tool in preventing escalation of doses
      into ranges associated with increased mortality risk.

PMID- 24290445
TI  - Comparative responsiveness of verbal and numerical rating scales to measure pain
      intensity in patients with chronic pain.
AB  - Verbal rating scale (VRS) and numerical rating scale (NRS) are regularly used to
      assess and monitor pain in chronic pain patients. Although the NRS has been
      generally preferred, limited comparative responsiveness evidence was reported.
      This study compared the responsiveness of VRS and NRS measuring current pain and
      investigated the influence of different references (ie, worst, least, average,
      and current pain or their composite) on the NRSs' responsiveness. Two hundred
      fifty-four chronic pain patients attended a 10-day pain self-management program
      and were assessed with two 6-point VRSs (assessing current pain) and four 11
      point NRSs (assessing worst, least, average, and current pain) at pre- and
      posttreatment. A patient-reported rating of pain improvement was used as the
      criterion for standardized response mean and receiver operating characteristic
      curve analyses. Results showed that the VRSs and NRSs exhibited small
      responsiveness in all patients, but the magnitude of responsiveness became
      moderate to large in patients with improved pain. However, in patients with pain
      improvements, the NRS current pain item and composite score (made up of the 4
      pain items) were found to have significantly larger responsiveness and greater
      discriminatory ability to detect the presence of improvement than other current
      pain VRSs and the NRSs assessing worst, least, and average pain. Potential
      implications for clinical practice are discussed. PERSPECTIVE: This study shows
      that the current pain and composite NRSs were more responsive than the current
      pain VRSs and the NRSs measuring other individual pain references in patients
      with improved pain, undertaking a short-term, self-management program. The
      results help inform the selection of pain intensity measures in studies using
      similar types of intervention.

PMID- 24290444
TI  - Unraveling the effects of plasticity and pain on personality.
AB  - Chronic pain resulting from physical stressors is often accompanied by
      psychological disorders such as depression. Although depressive disorders are
      associated with changes in brain anatomy, it remains unknown if changes in brain
      anatomy associated with increased state depression levels also occur in patients
      with chronic pain. When individuals are experiencing physical stressors such as
      ongoing pain, depressive personality traits may predispose them to develop
      depressive states. The aim of this study was to use brain morphometry to
      determine the interaction among chronic pain, state and trait depression, and
      regional brain structure. We investigated regional gray matter volume in 42
      chronic pain patients and 35 controls using voxel-based morphometry of T1
      weighted anatomical images. Significant relationships between regional gray
      matter volume and state or trait depressive values were determined. In chronic
      pain patients, state depression scores were significantly correlated to subtle
      changes in the thalamus and the cingulate, dorsolateral prefrontal, and
      hippocampal cortices. These same brain regions were also significantly correlated
      to trait depressive scores. Unexpectedly, gray matter volumes in these regions
      were not correlated to trait depressive scores in healthy controls. Because trait
      depressive values were not correlated to gray matter in controls, but were so in
      chronic pain patients, these data strongly suggest that subtle changes in brain
      anatomy can evoke changes in individuals' trait depression values. If these
      regional gray matter changes are severe enough, changes in an individual's
      personality trait may result. PERSPECTIVE: This study demonstrates anatomical
      brain alterations associated with both state and trait depression in chronic pain
      patients. Because our study reveals that trait depression is not correlated to
      the anatomy of these regions in healthy controls, ongoing pain itself may result
      in anatomical changes that in turn can alter an individual's personality.

PMID- 24290442
TI  - The association of sleep and pain: an update and a path forward.
AB  - Ample evidence suggests that sleep and pain are related. However, many questions
      remain about the direction of causality in their association, as well as
      mechanisms that may account for their association. The prevailing view has
      generally been that they are reciprocally related. The present review critically
      examines the recent prospective and experimental literature (2005-present) in an
      attempt to update the field on emergent themes pertaining to the directionality
      and mechanisms of the association of sleep and pain. A key trend emerging from
      population-based longitudinal studies is that sleep impairments reliably predict
      new incidents and exacerbations of chronic pain. Microlongitudinal studies
      employing deep subjective and objective assessments of pain and sleep support the
      notion that sleep impairments are a stronger, more reliable predictor of pain
      than pain is of sleep impairments. Recent experimental studies suggest that sleep
      disturbance may impair key processes that contribute to the development and
      maintenance of chronic pain, including endogenous pain inhibition and joint pain.
      Several biopsychosocial targets for future mechanistic research on sleep and pain
      are discussed, including dopamine and opioid systems, positive and negative
      affect, and sociodemographic factors. PERSPECTIVE: This critical review examines
      the recent prospective and experimental research (2005-present) on the
      association of sleep and pain in an attempt to identify trends suggestive of
      directionality and potential mechanisms. An update on this literature is needed
      to guide future clinical efforts to develop and augment treatments for chronic
      sleep disturbance and chronic pain.

PMID- 24290446
TI  - Psychophysical tests as predictors of back pain chronicity in primary care.
AB  - If persons at risk of developing chronic pain could be identified early in a pain
      episode, treatment could be tailored on the basis of risk. Responses to
      psychophysical tests differ in persons with chronic pain vs pain-free controls
      and thus appear promising as indicators of susceptibility to chronic pain. In a
      cohort of 157 patients making their first primary care visit during a back pain
      episode, we explored the relationships of psychophysical test responses (pressure
      pain thresholds at low back and thenar sites, cold pressor pain ratings,
      conditioned pain modulation, and mechanical temporal summation) to baseline
      measures of pain and psychological distress and assessed whether test responses
      predicted clinically significant back pain 4 months later. Examiner-standardized
      pressure pain thresholds were significantly (P < .05) correlated with baseline
      back pain severity and diffuseness of bodily pain (Pearson correlations = -.21 to
      -.35). Lower baseline pressure pain thresholds significantly predicted back pain
      at 4 months (odds ratio [95% confidence interval]: low back, .66 [.44, .96];
      thenar, .62 [.40, .92]); however, after controlling for participant age and sex,
      these associations were no longer significant. Cold pressor pain, conditioned
      pain modulation, and mechanical temporal summation were not significant
      predictors of 4-month back pain in either model. PERSPECTIVE: Some psychophysical
      test responses have been found to differ in persons with chronic pain vs pain
      free controls. In this prospective study, psychophysical test responses had
      limited utility for predicting which primary care back pain patients would have
      clinically significant chronic pain 4 months later.

PMID- 24290447
TI  - TGF-beta1 attenuates spinal neuroinflammation and the excitatory amino acid
      system in rats with neuropathic pain.
AB  - Previous studies have reported that the intrathecal (i.t.) administration of
      transforming growth factor beta1 (TGF-beta1) prevents and reverses neuropathic
      pain. However, only limited information is available regarding the possible role
      and effects of spinal TGF-beta1 in neuropathic pain. We aimed to investigate the
      antinociceptive effects of exogenous TGF-beta1 on chronic constriction injury
      (CCI)-induced neuropathic pain in rats. We demonstrated that sciatic nerve injury
      caused a downregulation of endogenous TGF-beta1 levels on the ipsilateral side of
      the lumbar spinal dorsal gray matter, and that the i.t. administration of TGF
      beta1 (.01-10 ng) significantly attenuated CCI-induced thermal hyperalgesia in
      neuropathic rats. TGF-beta1 significantly inhibited CCI-induced spinal
      neuroinflammation, microglial and astrocytic activation, and upregulation of
      tumor necrosis factor-alpha. Moreover, i.t. TGF-beta1 significantly attenuated
      the CCI-induced downregulation of glutamate transporter 1, the glutamate
      aspartate transporter, and the excitatory amino acid carrier 1 on the ipsilateral
      side. Furthermore, i.t. TGF-beta1 significantly decreased the concentrations of 2
      excitatory amino acids, aspartate and glutamate, in the spinal dialysates in CCI
      rats. In summary, we conclude that the mechanisms of the antinociceptive effects
      of i.t. TGF-beta1 in neuropathy may include attenuation of spinal
      neuroinflammation, attenuation, or upregulation of glutamate transporter
      downregulation, and a decrease of spinal extracellular excitatory amino acids.
      PERSPECTIVE: Clinically, medical treatment is usually initiated after the onset
      of intractable pain. Therefore, in the present study, i.t. TGF-beta1 was designed
      to be administered 2 weeks after the establishment of CCI pain. Compared to the
      continuous TGF-beta1 infusion mode, single-dose administration seems more
      convenient and practical to use.

PMID- 24290448
TI  - Prescribing practices amid the OxyContin crisis: examining the effect of print
      media coverage on opioid prescribing among physicians.
AB  - The pain medication OxyContin (hereafter referred to as oxycodone extended
      release) has been the subject of sustained, and largely negative, media attention
      in recent years. We sought to determine whether media coverage of oxycodone
      extended release in North American newspapers has led to changes in prescribing
      of the drug in Nova Scotia, Canada. An interrupted time-series design examined
      the effect of media attention on physicians' monthly prescribing of opioids. The
      outcome measures were, for each physician, the monthly proportions of all opioids
      prescribed and the proportion of strong opioids prescribed that were for
      oxycodone extended release. The exposure of interest was media attention defined
      as the number of articles published each month in 27 North American newspapers.
      Variations in media effects by provider characteristics (specialty, prescribing
      volume, and region) were assessed. Within-provider changes in the prescribing of
      oxycodone extended release in Nova Scotia were observed, and they followed
      changes in media coverage. Oxycodone extended release prescribing rose steadily
      prior to receiving media attention. Following peak media attention in the United
      States, the prescribing of oxycodone extended release slowed. Likewise, following
      peak coverage in Canadian newspapers, the prescribing of oxycodone extended
      release declined. These patterns were observed across prescriber specialties and
      by prescriber volume, though the magnitude of change in prescribing varied.
      PERSPECTIVE: This study demonstrates that print media reporting of oxycodone
      extended release in North American newspapers, and its continued portrayal as a
      social problem, coincided with reductions in the prescribing of oxycodone
      extended release by physicians in Nova Scotia.

PMID- 24290450
TI  - Migraine-related gray matter and white matter changes at a 1-year follow-up
      evaluation.
AB  - To assess the longitudinal gray matter (GM) and white matter (WM) changes between
      repeated observations 1 year apart in a group of the early clinical stage of
      migraine patients without aura, and to explore the relationship of such
      structural changes with headache activity, we studied patients newly diagnosed
      with episodic migraine lasting 8 to 14 weeks. Optimized voxel-based morphometry
      and tract-based spatial statistical analyses were used to evaluate changes in GM
      and WM by using 3-dimensional T1-weighted and diffusion-tensor imaging,
      respectively. At the 1-year follow-up examination, GM reduction was observed in
      the dorsolateral and medial part of the superior frontal gyrus, orbitofrontal
      cortex, hippocampus, precuneus, and primary and secondary somatosensory cortices.
      No significant differences were found in the fractional anisotropy and
      longitudinal, radial, and mean diffusivity of WM in migraine patients without
      aura within a year. Negative results were found for the association between
      changes in headache activity parameters and GM. Our results indicated that the GM
      and WM changed in different pathophysiological conditions of migraine patients
      without aura. The WM probably evolves slowly in the course of migraine
      chronicity. PERSPECTIVE: Our study found early involvement of GM reduction of
      sensory-discriminative brain regions in the pathologic process of migraine, but
      the WM did not exhibit significant changes in the same time interval. GM
      reduction in sensory-discriminative brain regions may characterize the
      pathophysiological features of migraine patients without aura in its early stage.

PMID- 24290449
TI  - Pain prevalence and trajectories following pediatric spinal fusion surgery.
AB  - Factors contributing to pain following surgery are poorly understood, with
      previous research largely focused on adults. With approximately 6 million
      children undergoing surgery each year, there is a need to study pediatric
      persistent postsurgical pain. The present study includes patients with adolescent
      idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospective,
      multicentered registry examining postsurgical outcomes. The Scoliosis Research
      Society Questionnaire-Version 30, which includes pain, activity, mental health,
      and self-image subscales, was administered to 190 patients prior to surgery and
      at 1 and 2 years postsurgery. A subset (n = 77) completed 5-year postsurgery
      data. Pain prevalence at each time point and longitudinal trajectories of pain
      outcomes derived from SAS PROC TRAJ were examined using analyses of variance and
      post hoc pairwise analyses across groups. Thirty-five percent of patients
      reported pain in the moderate to severe range presurgery. One year postoperation,
      11% reported pain in this range, whereas 15% reported pain at 2 years
      postsurgery. At 5 years postsurgery, 15% of patients reported pain in the
      moderate to severe range. Among the 5 empirically derived pain trajectories,
      there were significant differences on self-image, mental health, and age.
      Identifying predictors of poor long-term outcomes in children with postsurgical
      pain may prevent the development of chronic pain into adulthood. PERSPECTIVE:
      This investigation explores the prevalence of pediatric pain following surgery,
      up to 5 years after spinal fusion surgery. Five pain trajectories were identified
      and were distinguishable on presurgical characteristics of age, mental health,
      and self-image. This is the largest study to examine longitudinal pediatric pain
      trajectories after surgery.

PMID- 24290451
TI  - The role of trait mindfulness in the pain experience of adolescents.
AB  - Trait mindfulness appears to mitigate pain among adult clinical populations and
      has a unique relationship with pain catastrophizing. However, little is
      understood about this phenomenon among adolescents. The association between trait
      mindfulness and pain in both real-world and experimental contexts was examined in
      a community sample of adolescents. Participants were 198 adolescents who
      completed measures of trait mindfulness, pain catastrophizing, and pain
      interference, as well as an interview on day-to-day pain before undergoing an
      acute experimental pain task. Following the task, they provided ratings of pain
      intensity and state catastrophizing. Results showed that with regard to day-to
      day pains, mindfulness was a significant and unique predictor of pain
      interference, and this relationship was partially mediated by pain
      catastrophizing. Mindfulness also had an indirect relationship with experimental
      pain intensity and tolerance. These associations were mediated by catastrophizing
      during the pain task. These findings highlight the association between trait
      mindfulness and both real-world and experimental pain and offer insight into how
      mindfulness may affect pain among youth. Findings are discussed in the context of
      current psychological models of pediatric pain and future avenues for research.
      PERSPECTIVE: This article highlights the association between trait mindfulness
      and pain variables among adolescents in both real-world and experimental pain
      settings. These findings offer further evidence of the unique relationship
      between trait mindfulness and pain catastrophizing in affecting pain variables
      across pain contexts and populations.

PMID- 24290453
TI  - Here and there/global burden of disease.

PMID- 24290452
TI  - Catechol-O-methyltransferase Val158Met polymorphism (rs4680) is associated with
      pain in multiple sclerosis.
AB  - Alterations in the rs4680 Val158Met polymorphism are associated with the presence
      of pain. No study has investigated the role of Val158Met polymorphism in the
      susceptibility to exhibit pain in multiple sclerosis (MS). Our aim was to
      investigate the relationship between Val158Met polymorphism (rs4680) and the
      presence of pain in MS. One hundred eight (n = 108) patients (mean age: 44 +/- 8
      years) with a definitive diagnosis of MS and 108 matched controls participated.
      Fifty-eight patients (54%) had pain and 50 (46%) did not report pain. After
      amplifying Val158Met polymorphisms by polymerase chain reactions, rs4680 genotype
      frequencies and allele distributions were calculated. We classified individuals
      according to their Val158Met polymorphism: Val/Val, Val/Met, and Met/Met. The
      results showed that distribution of rs4680 Val158Met genotypes was not
      significantly different between individuals with MS in general and healthy people
      (chi2 = 2.212, P = .331). When we differentiate MS patients with pain and those
      without pain, the prevalence of Val158Met genotypes was significantly different
      (chi2 = 9,610, P = .046): Patients experiencing pain exhibited higher prevalence
      of Met/Met genotype than those without pain and healthy controls. Current results
      suggest that the Met allele of Val158Met polymorphism could be a potential risk
      factor for the development of pain in MS but not for the predisposition of MS
      itself. PERSPECTIVE: This study suggests that the Val158Met polymorphism is
      associated with the presence of pain in MS, but it is not a risk factor for MS
      itself because the presence of the Met/Met genotype was more prevalent in those
      patients with pain. This study provides further evidence of potential genetic
      factors that predispose patients with MS to develop pain.

PMID- 24290454
TI  - Engendering identity.

PMID- 24290455
TI  - How should we interpret and value the pursuit of blood-based biomarkers for
      autism spectrum disorders?

PMID- 24290456
TI  - A 60-year climb on the mountain of nosology.

PMID- 24290457
TI  - Stimulant misuse: is the pursuit of happiness by youth overrated?

PMID- 24290458
TI  - Can children with callous and unemotional traits be treated successfully?

PMID- 24290459
TI  - Protecting adolescents from self-harm: a critical review of intervention studies.
AB  - OBJECTIVE: To review the studies that test treatments targeting adolescent
      suicidal ideation, suicide attempts, or self-harm, and to make recommendations
      for future intervention development. METHOD: The extant randomized clinical
      trials that aim to reduce the intensity of suicidal ideation or the recurrence of
      suicide attempts or self-harm were reviewed with respect to treatment components,
      comparison treatments, sample composition, and outcomes. RESULTS: The majority of
      studies that showed any effect on suicidal ideation, attempts, or self-harm had
      some focus on family interactions or nonfamilial sources of support. Two of the
      most efficacious interventions also provided the greatest number of sessions.
      Some other treatment elements associated with positive effects include addressing
      motivation for treatment and having explicit plans for integrating the
      experimental treatment with treatment as usual. In many studies, suicidal events
      tend to occur very early in the course of treatment prior to when an effective
      "dose" of treatment could be delivered. Important factors that might mitigate
      suicidal risk, such as sobriety, healthy sleep, and promotion of positive affect,
      were not addressed in most studies. CONCLUSION: Interventions that can front-load
      treatment shortly after the suicidal crisis, for example, while adolescent
      suicide attempters are hospitalized, may avert early suicidal events. Treatments
      that focus on the augmentation of protective factors, such as parent support and
      positive affect, as well as the promotion of sobriety and healthy sleep, may be
      beneficial with regard to the prevention of recurrent suicidal ideation,
      attempts, or self-harm in adolescents.

PMID- 24290460
TI  - Medical and nonmedical use of prescription stimulants: results from a national
      multicohort study.
AB  - OBJECTIVE: To examine the lifetime prevalence of medical and nonmedical use of
      prescription stimulants (e.g., Adderall, Concerta, Ritalin, Dexedrine) among high
      school seniors in the United States, and to assess substance use behaviors (i.e.,
      cigarette smoking, binge drinking, marijuana, and other drug use) based on
      lifetime histories of medical and nonmedical use of prescription stimulants.
      METHOD: Nationally representative samples of high school seniors from the
      Monitoring the Future study were surveyed via self-administered questionnaires.
      The sample consisted of 4,572 individuals (modal age 18 years) from 2 independent
      cohorts (2010 and 2011) and represented a population that was 50% female, 57%
      white, 12% African-American, 13% Hispanic, and 18% other. RESULTS: The lifetime
      prevalence of medical use of prescription stimulants was 9.5%, and the lifetime
      nonmedical use of prescription stimulants was also 9.5%. Among those who were
      ever prescribed stimulants, approximately 59.3% reported medical use only, 22.9%
      reported medical use before nonmedical use, and 17.8% reported nonmedical use
      before medical use. The odds of substance use behaviors generally did not differ
      between medical users only and non-users. In contrast, the odds of substance use
      behaviors were greater among nonmedical users only and medical users who reported
      any history of nonmedical use relative to nonusers. CONCLUSIONS: About 1 in every
      6 high school seniors in the United States has ever had some exposure to
      prescription stimulants, either medically or nonmedically. Health care
      professionals should carefully screen and monitor adolescents, because the risk
      for substance abuse is directly associated with a history of nonmedical use of
      prescription stimulants.

PMID- 24290462
TI  - Preschool anxiety disorders in pediatric primary care: prevalence and
      comorbidity.
AB  - OBJECTIVE: We sought to establish prevalence rates and detail patterns of
      comorbidity for generalized anxiety disorder, separation anxiety disorder, and
      social phobia in preschool-aged children. METHOD: The Duke Preschool Anxiety
      Study, a screen-stratified, cross-sectional study, drew from pediatric primary
      care and oversampled for children at risk for anxiety. A total of 917 parents of
      preschool children (aged 2-5 years) completed the Preschool Age Psychiatric
      Assessment. RESULTS: Generalized anxiety disorder, separation anxiety disorder,
      and social phobia are common in preschool-aged children attending pediatric
      primary care. Three-fourths of preschoolers with an anxiety disorder only had a
      single anxiety disorder. Generalized anxiety disorder displayed the greatest
      degree of comorbidity: with separation anxiety disorder (odds ratio [OR] = 4.1,
      95% CI = 2.0-8.5), social phobia (OR = 6.4, 95% CI = 3.1-13.4), disruptive
      behavior disorders (OR = 5.1, 95% CI = 1.6-15.8), and depression (OR = 3.7, 95%
      CI = 1.1-12.4). CONCLUSIONS: The weakness of association between generalized
      anxiety disorder and depression stands in contrast to substantial associations
      between these 2 disorders reported in older individuals. Attenuated associations
      in preschool-aged children could translate into clinical opportunities for
      targeted early interventions, aimed at modifying the developmental trajectory of
      anxiety disorders.

PMID- 24290461
TI  - Callous-unemotional traits, proactive aggression, and treatment outcomes of
      aggressive children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Stimulant treatment improves impulse control among children with
      attention-deficit/hyperactivity disorder (ADHD). Decreased aggression often
      accompanies stimulant pharmacotherapy, suggesting that impulsiveness is integral
      to aggressive behavior in these children. However, children with high callous
      unemotional (CU) traits and proactive aggression may benefit less from ADHD
      pharmacotherapy, because their aggressive behavior seems more purposeful and
      deliberate. This study's objective was to determine whether pretreatment CU
      traits and proactive aggression affect treatment outcomes among aggressive
      children with ADHD receiving stimulant monotherapy. METHOD: We implemented a
      stimulant optimization protocol with 160 children 6 to 13 years of age (mean [SD]
      age of 9.31 [2.02] years; 78.75% male) with ADHD, oppositional defiant or conduct
      disorder, and significant aggressive behavior. Family-focused behavioral
      intervention was provided concurrently. The primary outcome was the Retrospective
      Modified Overt Aggression Scale. The Antisocial Process Screening Device and the
      Aggression Scale, also completed by parents, measured CU traits and proactive
      aggression, respectively. Analyses examined moderating effects of CU traits and
      proactive aggression on outcomes. RESULTS: In all, 82 children (51%) experienced
      remission of aggressive behavior. Neither CU traits nor proactive aggression
      predicted remission (CU traits: odds ratio [OR] = 0.94, 95% CI = 0.80-1.11;
      proactive aggression, OR = 1.05, 95% CI = 0.86-1.29). Children whose overall
      aggression remitted showed decreases in CU traits (effect size = -0.379, 95% CI =
      -0.60 to -0.16) and proactive aggression (effect size = -0.463, 95% CI = -0.69 to
      -0.23). CONCLUSIONS: Findings suggest that pretreatment CU traits and proactive
      aggression do not forecast worse outcomes for aggressive children with ADHD
      receiving optimized stimulant pharmacotherapy. With such treatment, CU traits and
      proactive aggression may decline alongside other behavioral improvements.
      Clinical trial registration information--Medication Strategies for Treating
      Aggressive Behavior in Youth With Attention Deficit Hyperactivity Disorder;
      http://clinicaltrials.gov/; NCT00228046; and Effectiveness of Combined Medication
      Treatment for Aggression in Children With Attention Deficit With Hyperactivity
      Disorder (The SPICY Study); http://clinicaltrials.gov/; NCT00794625.

PMID- 24290463
TI  - Preschool irritability: longitudinal associations with psychiatric disorders at
      age 6 and parental psychopathology.
AB  - OBJECTIVE: There is increasing scientific and clinical attention to chronic
      irritability in youth. However, little is known about the predictive validity and
      clinical significance of chronic irritability during early childhood. This
      prospective, longitudinal study examined associations of chronic irritability
      with psychiatric disorders and parental psychopathology in a large community
      sample of preschoolers. METHOD: Four hundred sixty-two preschool-age children
      were assessed at 3 and 6 years of age. Child psychopathology was assessed at
      baseline (3 years) and follow-up (6 years) using a diagnostic interview, the
      Preschool Age Psychiatric Assessment, with parents. Items from the Preschool Age
      Psychiatric Assessment were used to create a dimensional measurement of chronic
      irritability. Parental psychopathology was assessed with a diagnostic interview
      at baseline. RESULTS: Chronic irritability was concurrently associated with a
      wide range of psychiatric disorders and functional impairment at 3 and 6 years of
      age. Irritability at 3 years predicted depression, oppositional defiant disorder,
      and functional impairment at 6 years after controlling for baseline disorders.
      Irritability also was associated with parental depression and anxiety.
      CONCLUSIONS: Findings underscore the central role of irritability in early
      emerging mental health problems. They are consistent with longitudinal studies in
      older youth indicating that chronic irritability predicts later depression and
      anxiety and support the importance of early detection and interventions targeting
      preschool irritability.

PMID- 24290464
TI  - Emotional face processing in pediatric bipolar disorder: evidence for functional
      impairments in the fusiform gyrus.
AB  - OBJECTIVE: Pediatric bipolar disorder involves poor social functioning, but the
      neural mechanisms underlying these deficits are not well understood. Previous
      neuroimaging studies have found deficits in emotional face processing localized
      to emotional brain regions. However, few studies have examined dysfunction in
      other regions of the face processing circuit. This study assessed hypoactivation
      in key face processing regions of the brain in pediatric bipolar disorder.
      METHOD: Youth with a bipolar spectrum diagnosis (n = 20) were matched to a
      nonbipolar clinical group (n = 20), with similar demographics and comorbid
      diagnoses, and a healthy control group (n = 20). Youth participated in a
      functional magnetic resonance imaging (fMRI) scanning which employed a task
      irrelevant emotion processing design in which processing of facial emotions was
      not germane to task performance. RESULTS: Hypoactivation, isolated to the
      fusiform gyrus, was found when viewing animated, emerging facial expressions of
      happiness, sadness, fearfulness, and especially anger in pediatric bipolar
      participants relative to matched clinical and healthy control groups.
      CONCLUSIONS: The results of the study imply that differences exist in visual
      regions of the brain's face processing system and are not solely isolated to
      emotional brain regions such as the amygdala. Findings are discussed in relation
      to facial emotion recognition and fusiform gyrus deficits previously reported in
      the autism literature. Behavioral interventions targeting attention to facial
      stimuli might be explored as possible treatments for bipolar disorder in youth.

PMID- 24290465
TI  - Resting state functional connectivity of the ventral attention network in
      children with a history of depression or anxiety.
AB  - OBJECTIVE: We examined whether depression and anxiety disorders in early
      childhood were associated with changes in resting state functional connectivity
      (RSFC) of the ventral attention network (VAN), and whether RSFC in the VAN was
      associated with alterations in attention specific to these disorders. Important
      clinical features of these illnesses, including changes in attention toward novel
      stimuli and changes in attention to stimuli of negative valence (threat/sad
      bias), indirectly implicate the VAN. METHOD: We collected resting state
      functional magnetic resonance imaging data in children aged 8 to 12 years. Data
      were volume censored to reduce artifact from submillimeter movement, resulting in
      analyzable data from 30 children with a history of depression and/or anxiety and
      42 children with no psychiatric history. We compared pairwise RSFC among the
      following VAN regions: right ventro-lateral prefrontal cortex (VLPFC), right
      posterior superior temporal gyrus (pSTG), and right ventral supramarginal gyrus
      (vSMG). We also collected measures of threat bias and current clinical symptoms.
      RESULTS: Children with a history of depression and/or anxiety had reduced RSFC
      among the regions of the VAN compared to children with no psychiatric history.
      The magnitude of VAN RSFC was correlated with measures of attention bias toward
      threat but not with current depressive, internalizing, or externalizing symptoms.
      No RSFC changes were detected between groups among homotopic left hemisphere
      regions. CONCLUSIONS: Disruption in the VAN may be an early feature of depression
      and anxiety disorders. VAN changes were associated with attention bias and
      clinical history but not with current symptoms of depression and anxiety.

PMID- 24290467
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with tic disorders.
AB  - Tic disorders, including Tourette's disorder, present with a wide range of
      symptom severity and associated comorbidity. This Practice Parameter reviews the
      evidence from research and clinical experience in the evaluation and treatment of
      pediatric tic disorders. Recommendations are provided for a comprehensive
      evaluation to include common comorbid disorders and for a hierarchical approach
      to multimodal interventions. 

PMID- 24290468
TI  - Rejuvenation: Editor's Annual Report-Volume 52, 2013.

PMID- 24290469
TI  - Hats off: Journal awards 2013.

PMID- 24290471
TI  - Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow
      proliferation mice.
AB  - To investigate the pharmacological effects of Danggui Buxue Tang (DBT) on immune
      mediated aplasia anemia mice. The model of immune-mediated aplasia anemia mice
      was induced by means of (60)Co gamma-ray irradiation and mixed cells of thymus
      and lymphnode of DBA/2 mice infusion through tail vein, the parameters tested
      indices were as following: blood picture, bone marrow nucleated cell count
      (BMNC), murine colony-forming unit-megakaryocytes (CFU-GM) of bone marrow cells,
      murine colony-forming unit-erthroid (CFU-E) and burst forming unit-erythroid (BFU
      E). The results showed that DBT could not only withstand significantly decreation
      of blood cells by immune-mediated, but also stimulate on the growth of bone
      marrow colony cell and increase the weight of hemopoietic progenitor of bone
      marrow. Therefore, DBT had an obvious treat effect on immune-mediated aplasia
      anemia models mice. 

PMID- 24290472
TI  - Effects of the root of Platycodon grandiflorum on airway mucin hypersecretion in
      vivo and platycodin D(3) and deapi-platycodin on production and secretion of
      airway mucin in vitro.
AB  - We investigated whether aqueous extract of the root of Platycodon grandiflorum A.
      de Candolle (APG), platycodinD(3) and deapi-platycodin significantly affect the
      production and secretion of airway mucin using in vivo and in vitro experimental
      models. Effect of APG was checked on hypersecretion of pulmonary mucin in sulfur
      dioxide-induced bronchitis in rats. Confluent NCI-H292 cells were pretreated with
      platycodinD(3) or deapi-platycodin for 30min and then stimulated with PMA
      (phorbol 12-myristate 13-acetate) for 24h. The MUC5AC mucin production and
      secretion were measured by ELISA. The results were as follows: (1) APG stimulated
      the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; (2)
      platycodinD(3) and deapi-platycodin inhibited the production of MUC5AC mucin
      induced by PMA from NCI-H292 cells, respectively; (3) however, platycodinD(3) and
      deapi-platycodin did not inhibit but stimulated the secretion of MUC5AC mucin
      induced by PMA from NCI-H292 cells, respectively. This result suggests that
      aqueous extract of P. grandiflorum A. de Candolle and the two natural products
      derived from it, platycodinD(3) and deapi-platycodin, can regulate the production
      and secretion of airway mucin and, at least in part, explains the traditional use
      of aqueous extract of P. grandiflorum A. de Candolle as expectorants in diverse
      inflammatory pulmonary diseases.

PMID- 24290473
TI  - William Shakespeare's neurology.
AB  - Many of Shakespeare's plays contain characters who appear to be afflicted by
      neurological or psychiatric disorders. Shakespeare, in his descriptive analysis
      of his protagonists, was contributing to the understanding of these disorders. In
      fact, Charcot frequently used Shakespearean references in his neurological
      teaching sessions, stressing how acute objective insight is essential to
      achieving expert clinical diagnosis. Charcot found in Shakespeare the same
      rigorous observational techniques for which he himself became famous. This
      chapter describes many of Shakespearean characters suffering from varied
      neurological disorders, including Parkinsonism, epilepsy, sleeping disturbances,
      dementia, headache, prion disease, and paralyses.

PMID- 24290474
TI  - Locked-in: the syndrome as depicted in literature.
AB  - Protagonists who are locked-in can be found throughout fiction, probably because
      being locked-in serves as a strong philosophical metaphor for human existence. In
      this chapter, three protagonists who are locked-in due to physical/medical
      reasons will be described. The fictitious stories of Noirtier from The Count of
      Monte Cristo by Alexandre Dumas and that of Madame Raquin from Therese Raquin by
      Emile Zola are followed by the real-life story of Jean-Dominique Bauby's The
      Diving Bell and the Butterfly. Dumas' Noirtier is considered the first
      description of the locked-in syndrome in literature, and Madame Raquin appears to
      be locked-in also, but her description leaves many questions. Bauby's
      autopathography is chosen from many several similar discourses as it contains
      cross-references to Noirtier, Dumas' prototype of the syndrome, but also because
      it is of high literary value. The similarities and remarkable differences between
      these three case reports of this existentialistically important state of being
      will be highlighted, with an emphasis on the focus of their narratives.

PMID- 24290475
TI  - Meningitis, a whirlpool of death: literary reflections and Russian cultural
      beliefs.
AB  - Meningitis is an inflammation of the meninges, the membranes that cover the
      central nervous system. The most frequent causes of the disease are viruses and
      bacteria. In the past, the disease was commonly referred to as "brain fever" or
      "brain inflammation," and extreme temperatures, sun, rain, mental distress, and
      other factors were believed to be its potent triggers. By the beginning of the
      twentieth century, these beliefs faded away in the United States and most western
      European countries. In contrast, some of these archaic notions persist in Russia,
      where cold air, draft, wet hair, and failure to cover one's head with a hat
      during winter are perceived as serious risks for contracting meningitis. These
      sentiments are reflected in the prose of Solzhenitsyn and other contemporary
      Russian authors. However, in the fictional literature of the nineteenth century,
      emotional or intellectual disturbances rather than the wrath of winter were
      portrayed worldwide as the most frequent cause of brain inflammation. Both
      physicians and laity blamed nervous breakdown or mental distress for the
      development of meningitis and the tragic deaths of the eminent Russian writer
      Gogol, talented poet Nadson, and heir to the Imperial throne Grand Duke Nicholas
      Romanov. Even in the twentieth century, esteemed Russian artists, including
      Pasternak, Paustovsky, and Roerich, highlighted this belief. Following the
      discovery of the infectious nature of meningitis, fictional depictions of the
      illness changed. While literary accounts of brain inflammation by the realists
      (e.g., Dostoevsky and Flaubert) were rather imprecise, the descriptions of the
      course and symptoms of meningitis by the modernists (e.g., Balmont, Hesse, and
      Huxley) became detailed and recognizable. Typically, the victim of the disease is
      a boy, and his imminent agony is preceded by immense suffering that devastates
      his parents. The dreadful experience of seeing children in the merciless clutches
      of meningitis had a profound personal effect on Maugham, Twain, and Russian
      philosopher Tikhomirov, changing their spiritual convictions. However, several
      authors, among them Avseenko, Davydov, Gazdanov, and Shmelyov, created uplifting
      stories of survival of the affliction. In this chapter, references to meningitis
      in the medical and fictional literature are explored through a cultural and
      historical prism, which may help readers to understand how and why this disease
      has held a special significance in the Russian psyche.

PMID- 24290476
TI  - Parkinsonism in poets and writers.
AB  - Parkinson disease is a severe degenerative disease, which is bewildering for its
      array of clinical features. Writers for the past five centuries have described
      the associated symptoms. Before the nineteenth century, Miguel de Cervantes wrote
      Don Quixote de la Mancha and William Shakespeare wrote several tragedies dealing
      with neurological manifestations that are characteristic of Parkinson disease.
      From the nineteenth century onward, writers including Charles Dickens, Samuel
      Beckett, Galway Kinnell, and Harold Pinter among others have showcased in their
      works classic manifestations of Parkinson disease. This literary attention has
      led to a greater awareness on the part of the general public regarding this
      disease and, in turn, has opened the doors to a better understanding of and a
      better respect for the patients affected by this disease.

PMID- 24290477
TI  - Neurosyphilitics and madmen: The French fin-de-siecle fictions of Huysmans,
      Lermina, and Maupassant.
AB  - This chapter considers a neurological approach to analyzing the decadent and
      fantastic fictions of the French fin-de-siecle. It focuses on three texts whose
      depictions of male nervosism were influenced by Charles Baudelaire's biography of
      Edgar Allan Poe and by contemporary medical discourses, including those of Jean
      Martin Charcot and George Miller Beard: Joris-Karl Huysmans' A Rebours (1884),
      Jules Lermina's Les Fous (1885), and Guy de Maupassant's Le Horla (1885-1887).
      Although these authors were philosophically antipositivist and antimaterialist,
      they used scientific theories of neurasthenia, neurodegeneration, and visual
      hallucination to probe the frontiers between body and spirit, the known and the
      unknowable.

PMID- 24290478
TI  - Charcot, la salpetriere, and hysteria as represented in European literature.
AB  - In this chapter, I describe the influence of Jean-Martin Charcot (1825-1893), his
      neurological school at the Salpetriere (Paris), and his teaching of hysteria on
      European literature. Many references to Charcot and descriptions of hysterical
      attacks are found not only in French naturalistic literature but also
      subsequently in naturalistic novels from other European countries (the
      Netherlands, Russia, Scandinavian countries, Spain, Italy, and Germany) and
      furthermore in novels written in new literary movements that followed naturalism.
      At first, objective descriptions were presented, but in the periods that
      followed, in particular during the past decades, criticism, rather than objective
      descriptions, became the motivation for continuing to use Charcot and his
      teaching of hysteria as inspiration for novels and plays, although Charcot as an
      admired founder of neurology did not quite disappear, even in recent novels. It
      is quite impressive to observe how Charcot and his demonstrations of hysterical
      attacks still resound throughout European literature, even after more than a
      century.

PMID- 24290479
TI  - Historical and literary roots of Munchhausen syndromes: as intriguing as the
      syndromes themselves.
AB  - Hieronymus Carl Friedrich Freiherr von Munchhausen (1720-1797) was a famous
      eighteenth-century teller of extravagant stories. In 1785, Rudolph Erich Raspe
      anonymously published the first book-form edition of Munchhausen's Tales, and a
      German translation was made available by Gottfried August Burger the following
      year. Since that time, these adventures remained a best seller, and the name of
      the Baron was twice referred to in psychiatric terminology: "Munchhausen
      syndrome" coined by Richard Asher in 1951 and "Munchhausen syndrome by proxy"
      coined by Roy Meadow in 1977. This chapter examines the legitimacy of these terms
      in the light of historical and literary records and analyzes the synonyms or
      clinical types as found in medical publications.

PMID- 24290480
TI  - The Alice in Wonderland syndrome.
AB  - The Alice in Wonderland syndrome is a term applied to altered bizarre perceptions
      of size and shapes of a patient's body and illusions of changes in the forms,
      dimensions, and motions of objects that a patient with this syndrome encounters.
      These metamorphopsias arise during complex partial seizures, migraine headaches,
      infections, and intoxications. The illusions and hallucinations resemble the
      strange phenomena that Alice experienced in Lewis Carroll's Alice's Adventures in
      Wonderland. Charles Lutwidge Dodgson, whose nom de plume was Lewis Carroll,
      experienced metamorphopsias. He described them in the story that he wrote for
      Alice Liddell and her two sisters after he spun a tale about a long and strange
      dream that the fictional Alice had on a warm summer day. The author of this
      chapter suggests that Dodgson suffered from migraine headaches and used these
      experiences to weave an amusing tale for Alice Liddell. The chapter also
      discusses the neurology of mercury poisoning affecting the behavior of Mad Hatter
      character. The author suggests that the ever-somnolent Dormouse suffered from
      excessive daytime sleepiness due to obstructive sleep apnea.

PMID- 24290481
TI  - Tomas Transtromer's stroke of genius: language but no words.
AB  - In 1990, the widely acclaimed Swedish poet Tomas Transtromer lost his speech and
      the ability to use his right hand as a result of a stroke. As if anticipating his
      own fate, in 1974, he referred in his longest poem Baltics the story of the
      Russian composer Vissarion Shebalin who suffered the same symptoms as Transtromer
      following a brain bleed: "Then, cerebral hemorrhage: paralysis on the right side
      with aphasia." An amateur pianist himself, Transtromer carried on playing left
      handed piano pieces after the stroke. In spite of a severe nonfluent dysphasia
      with dysgraphia, Transtromer kept producing a poetic language of the highest
      caliber in accordance with his 1979 no less prophetic verse "language but no
      words." And through music and poetry, overcame the great communication barriers
      imposed by a large dominant hemispheric stroke. A nonprolific writer before the
      stroke, after it Transtromer became disproportionately brief compared to his
      prestroke production, confining most of his poetry to the agrammatical and
      telegraphic haiku style.

PMID- 24290482
TI  - The cruelty and failings of therapies for neurological diseases in French
      literature.
AB  - In this chapter, excerpts from famous or little-known works of French literature
      are used to illustrate how eighteenth- and nineteenth-century physicians tried to
      treat neuropsychiatric illnesses. Although the causes were unknown to them, they
      did not hesitate to inflict suffering on their patients, who were often in an
      appalling condition to begin with. Novelists such as Gustave Flaubert, Alphonse
      Daudet, the Goncourt brothers, Georges Simenon, and Celine applied their writing
      talents to describing the use of leeches, bloodletting, vibratory treatments,
      suspension of the body, multiple painful injections, and brutal electrotherapy.
      These writers reveal how physicians used their imaginations not only boundlessly
      but also without pity, to treat their patients. Each literary work is presented
      with the medical justifications of the time, for example, the explanations of
      Cruveilhier, Charcot, Brown-Sequard, Sollier, Vincent, and Roussy.

PMID- 24290483
TI  - Portrayals of lobotomy in American and Swedish media.
AB  - Psychosurgery has a long history dating back to the 1880s when Gottlieb
      Burckhardt performed focal cerebral cortical excisions on the brains of six
      patients diagnosed with schizophrenia. His operations were vividly contested by
      the medical community of the time. In 1936, when Walter J. Freeman and James W.
      Watts performed their initial prefrontal lobotomies in the United States, they
      were met with some professional opposition from superintendents, who would not
      provide them with patients for the operation. However, Freeman and Watts managed
      to cope well with the opponents. In newspapers and magazines, the curiosity for
      lobotomy was obvious. Freeman was instrumental in the way he promoted lobotomy,
      and he evoked the interest of the press and the journalists for this new surgical
      treatment on mental illness, something that he regarded as a medico-historical
      breakthrough. In this chapter, the portrayal of lobotomy in American and Swedish
      newspapers and magazines is explored and analyzed. How did journalists write
      about lobotomy for the public in the years spanning 1936 to 1959, a period in
      which the American and Swedish presses appeared inclined to describe the positive
      effects of lobotomy, while neglecting the negative and fatal consequences of the
      operation. There are not only similarities but also interesting differences
      between the Swedish and the American articles depicting lobotomy. The media can
      be a powerful factor in the construction of "facts," which can significantly
      affect decisions made by people about their health issues.

PMID- 24290484
TI  - Electroconvulsive therapy (ECT) in literature: Sylvia Plath's The Bell Jar.
AB  - Sylvia Plath's well-known novel, The Bell Jar, recounts her experience of a
      severe depressive episode. In the novel, the protagonist is treated with
      electroconvulsive therapy (ECT), as was Plath in life. The first ECT is given in
      the now-obsolete "unmodified" form, without general anesthesia. Later in the
      story, she receives ECT again, this time with full general anesthesia and muscle
      relaxation, as is the standard of care today. This chapter examines how the
      novelistic descriptions of the treatment compare with actual clinical practice.

PMID- 24290485
TI  - Literature, neurology, and neuroscience: neurological and psychiatric disorders.
      Preface.

PMID- 24290486
TI  - Online sources of herbal product information.
AB  - Herbal products are commonly used to treat clinical conditions and are often
      purchased online without the supervision of a healthcare provider. The use of
      herbals remains controversial because of widespread exaggerated claims of
      clinical efficacy and safety. We conducted an online search of 13 common herbals
      (including black cohosh, echinacea, garlic, ginkgo, ginseng, green tea, kava, saw
      palmetto, and St John's wort) and reviewed the top 50 Web sites for each using a
      Google search. We analyzed clinical claims, warnings, and other safety
      information. A total of 1179 Web sites were examined. Less than 8% of retail
      sites provided information regarding potential adverse effects, drug
      interactions, and other safety information; only 10.5% recommended consultation
      with a healthcare professional. Less than 3% cited scientific literature to
      accompany their claims. Key safety information is still lacking from many online
      sources of herbal information. Certain nonretail site types may be more reliable,
      but physicians and other healthcare professionals should be aware of the variable
      quality of these sites to help patients make more informed decisions. 

PMID- 24290488
TI  - Links between occupational activities and depressive mood in young adult
      populations.
AB  - BACKGROUND: To examine how occupational activities (work, school), separation
      from parents, environmental conditions, stressors ad social insertion affect on
      the prevalence of Major Depressive Disorder (MDD) and mental health care-seeking
      among young adults. METHODS: Cross-sectional study conducted in two samples: 1)
      19,136 subjective representative of the US non-institutionalized general
      population including 2082 18-26 y.o. subjects. 2) 2196 subjects representative of
      the students' population living on an university campus. Telephone interviews
      were realized using the Sleep-EVAL system to assess sleeping habits, general
      health, organic, sleep and mental disorders. RESULTS: One-month prevalence of
      depressed mood was similar between community and campus student groups (21.7% and
      23.4%), and less common than for working (23.6%) and non-working (28.2%) young
      adults in the community. One-month MDD was found in 12.0% of non-working young
      people, compared with 6.6% of young workers, 3.2% of on-campus students and 4.1%
      of students in the general population (p < 0.01). Correlates for depressive mood
      and MDD such as female gender, dissatisfaction with social life, obesity, living
      with pain and other factors were identified across groups. A minority of on
      campus (10.8%) and general population students (10.3%) had sought mental health
      services in the prior year. Individuals with MDD had higher rates of care-seeking
      than other young people (p < 0.001), high rates of psychotropic medication use (p
      < 0.001). CONCLUSIONS: Being a student appears to have a protective effect with
      respect to having depressive symptoms or MDD and seeking needed mental health
      care. Stress and social isolation were important determinants for depression
      among young adults.

PMID- 24290487
TI  - Gender differences in the effects of deployment-related stressors and pre
      deployment risk factors on the development of PTSD symptoms in National Guard
      Soldiers deployed to Iraq and Afghanistan.
AB  - OBJECTIVE: Although women in the military are exposed to combat and its
      aftermath, little is known about whether combat as well as pre-deployment
      risk/protective factors differentially predict post-deployment PTSD symptoms
      among women compared to men. The current study assesses the influence of combat
      related stressors and pre-deployment risk/protective factors on women's risk of
      developing PTSD symptoms following deployment relative to men's risk. METHOD:
      Participants were 801 US National Guard Soldiers (712 men, 89 women) deployed to
      Iraq or Afghanistan who completed measures of potential risk/protective factors
      and PTSD symptoms one month before deployment (Time 1) and measures of deployment
      related stressors and PTSD symptoms about 2-3 months after returning from
      deployment (Time 2). RESULTS: Men reported greater exposure to combat situations
      than women, while women reported greater sexual stressors during deployment than
      men. Exposure to the aftermath of combat (e.g., witnessing injured/dying people)
      did not differ by gender. At Time 2, women reported more severe PTSD symptoms and
      higher rates of probable PTSD than did men. Gender remained a predictor of higher
      PTSD symptoms after accounting for pre-deployment symptoms, prior interpersonal
      victimization, and combat related stressors. Gender moderated the association
      between several risk factors (combat-related stressors, prior interpersonal
      victimization, lack of unit support and pre-deployment concerns about life/family
      disruptions) and post-deployment PTSD symptoms. CONCLUSIONS: Elevated PTSD
      symptoms among female service members were not explained simply by gender
      differences in pre-deployment or deployment-related risk factors. Combat related
      stressors, prior interpersonal victimization, and pre-deployment concerns about
      life and family disruptions during deployment were differentially associated with
      greater post-deployment PTSD symptoms for women than men.

PMID- 24290489
TI  - Case-control risk factor study of methicillin-resistant Staphylococcus
      pseudintermedius (MRSP) infection in dogs and cats in Germany.
AB  - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged as a
      highly drug-resistant small animal veterinary pathogen. Although often isolated
      from outpatients in veterinary clinics, there is concern that MRSP follows a
      veterinary-hospital-associated epidemiology. This study's objective was to
      identify risk factors for MRSP infections in dogs and cats in Germany. Clinical
      isolates of MRSP cases (n=150) and methicillin-susceptible S. pseudintermedius
      (MSSP) controls (n=133) and their corresponding host signalment and medical data
      covering the six months prior to staphylococcal isolation were analysed by
      multivariable logistic regression. The identity of all MRSP isolates was
      confirmed through demonstration of S. intermedius-group specific nuc and mecA. In
      the final model, cats (compared to dogs, OR 18.5, 95% CI 1.8-188.0, P=0.01),
      animals that had been hospitalised (OR 104.4, 95% CI 21.3-511.6, P<0.001), or
      visited veterinary clinics more frequently (>10 visits OR 7.3, 95% CI 1.0-52.6,
      P=0.049) and those that had received topical ear medication (OR 5.1, 95% CI 1.8
      14.9, P=0.003) or glucocorticoids (OR 22.5, 95% CI 7.0-72.6, P<0.001) were at
      higher risk of MRSP infection, whereas S. pseudintermedius isolates from ears
      were more likely to belong to the MSSP-group (OR 0.09, 95% CI 0.03-0.34,
      P<0.001). These results indicate an association of MRSP infection with veterinary
      clinic/hospital settings and possibly with chronic skin disease. There was an
      unexpected lack of association between MRSP and antimicrobial therapy; this
      requires further investigation but may indicate that MRSP is well adapted to
      canine skin with little need for selective pressure.

PMID- 24290490
TI  - Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures.
AB  - Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is
      usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear
      during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy
      (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive
      event associated with fever. Genetic evidences for FS have suggested a complex
      mode of inheritance. Until now, to investigate genes at the genomic level,
      linkage analysis of familial forms and association studies have been performed,
      but nothing conclusive has been clearly related to FE and FS. As complex
      disorders, environmental factors might play a crucial role through epigenetic
      modification of key candidate genes such as CPA6, which encodes Carboxypeptidase
      A6, an extracellular protein. Therefore, we assessed DNA methylation in promoter
      of CPA6. In 186 FE patients and 92 FS patients compared to 93 healthy controls
      and 42 treated controls with antiepileptic drugs (AEDs), we found significant
      higher levels of methylation for epileptic patients. Methylation status were 3.4%
      (+/-3.2%) for FE cases and 4.3% (+/-3.5%) for FS cases, whereas healthy
      individuals and treated controls with AEDs showed a level of 0.8% (+/-2.9%) and
      1.5% (+/-3.9%), respectively (p<=0.001 for all comparisons). These results let
      growing evidence for DNA methylation involvment in FE and FS. 

PMID- 24290491
TI  - Application of the inner arm perforator flap in the management of axillary
      hidradenitis suppurativa.
AB  - Axillary hidradenitis suppurativa is a chronic and debilitating disease that
      primarily affects the axillae, perineum, and inframammary areas. Surgical removal
      of all the diseased skin constitutes the only efficient treatment. Covering an
      axillary fossa defect is challenging, due to the range of shoulder movement
      required. Indeed, shoulder movement may be compromised by scar contraction after
      inadequate surgery. The present study is the first to apply an inner arm
      perforator flap to the treatment of twelve axillary skin defects in 10 patients.
      The defect originated from extensive excision of recurrent hidradenitis
      suppurativa in the axilla. The technique used to cover the defect is a V-Y
      advancement flap or a propeller flap from the inner arm based on one to three
      perforators arising from the brachial artery or the superior ulnar collateral
      artery. The flap provides a tensionless wound closure and a generally
      unremarkable postoperative course in a short hospital stay. No major
      complications occurred. Two patients had minor delayed wound healing. Outcomes
      (including donor site morbidity, function and the cosmetic outcome) were very
      satisfactory in all cases. We consider that the inner arm perforator flap is a
      valuable new option for the reconstruction of axillary defects.

PMID- 24290492
TI  - Influence of presenting electrocardiographic findings on the treatment and
      outcomes of patients with non-ST-segment elevation myocardial infarction.
AB  - The influence of the presenting electrocardiographic (ECG) findings on the
      treatment and outcomes of patients with non-ST-segment elevation myocardial
      infarction (NSTEMI) has not been studied in contemporary practice. We analyzed
      the clinical characteristics, in-hospital management, and in-hospital outcomes of
      patients with NSTEMI in the Acute Coronary Treatment and Intervention Outcomes
      Network Registry-Get With The Guidelines (ACTION Registry-GWTG) according to the
      presenting ECG findings. A total of 175,556 patients from 485 sites from January
      2007 to September 2011 were stratified by the ECG findings on presentation: ST
      depression (n = 40,146, 22.9%), T-wave inversions (n = 24,627, 14%), transient ST
      segment elevation (n = 5,050, 2.9%), and no ischemic changes (n = 105,733,
      60.2%). Patients presenting with ST-segment depression were the oldest and had
      the greatest prevalence of major cardiac risk factors. Coronary angiography was
      performed most frequently in the transient ST-segment elevation group, followed
      by the T-wave inversion, ST-segment depression, and no ischemic changes groups.
      The angiogram revealed that patients with ST-segment depression had more left
      main, proximal left anterior descending, and 3-vessel coronary artery disease and
      underwent coronary artery bypass grafting most often. In contrast, patients with
      transient ST-segment elevation had 1-vessel CAD and underwent percutaneous
      coronary intervention the most. The unadjusted mortality was highest in the ST
      segment depression group, followed by the no ischemic changes, transient ST
      segment elevation, and T-wave inversion group. Adjusted mortality using the
      ACTION Registry-GWTG in-hospital mortality model with the no ischemic changes
      group as the reference showed that in-hospital mortality was similar in the
      transient ST-segment elevation (odds ratio 1.15, 95% confidence interval 0.97 to
      1.37; p = 0.10), higher in the ST-segment depression group (odds ratio 1.46, 95%
      confidence interval 1.37 to 1.54; p <0.0001), and lower in the T-wave inversion
      group (odds ratio 0.91, 95% confidence interval 0.83 to 0.99; p = 0.026). In
      conclusion, the clinical and angiographic characteristics and treatment and
      outcomes of patients with NSTEMI differed substantially according to the
      presenting ECG findings. Patients with ST-segment depression have a greater
      burden of co-morbidities and coronary atherosclerosis and have a greater risk of
      adjusted in-hospital mortality compared with the other groups. These findings
      highlight the importance of integrating the presenting ECG findings into the risk
      stratification algorithm for patients with NSTEMI. 

PMID- 24290493
TI  - Effect of telomere length on prognosis in men with acute coronary syndrome.
AB  - Telomere length is related to cellular aging and cardiovascular disease.
      Nevertheless, the specific role of cellular aging in this process is still
      unclear. The aim of this report was to analyze the prognostic value of telomere
      length in men admitted for acute coronary syndrome. Telomere length was measured
      by quantitative polymerase chain reaction in peripheral blood leukocytes of 203
      men classified into 2 groups: those aged 50 to 75 years and those >75 years.
      Clinical follow-up had been done for >600 days, and a prognostic combined event
      was defined. In men aged 50 to 75 years, we found a statistically significant
      worse prognosis in patients with short telomeres (log-rank: 5.22, p <0.05) but
      not in men >75 years (log-rank: 0.01, p = 0.91). Cox analysis confirmed short
      telomeres in men aged 50 to 75 years as an independent prognostic risk factor. In
      conclusion, telomere length is a good predictor of cardiovascular prognosis in
      men admitted for acute coronary syndrome, but this relation depends on the
      chronological age of the population studied.

PMID- 24290494
TI  - [Comments on the article: "Influence of short-stay units on the quality of health
      care in Spain. A systematic review"].

PMID- 24290495
TI  - Why are simple control options for Toxocara vitulorum not being implemented by
      cattle and buffalo smallholder farmers in South-East Asia?
AB  - Toxocara vitulorum infection in large ruminants is endemic in many tropical
      countries and particularly in South-East Asia. A single treatment of calves with
      pyrantel at 14-21 days of age effectively controls the parasite. Despite this
      treatment being readily available, T. vitulorum infection remains common and
      widespread. To understand drivers of effective control of T. vitulorum infection,
      we examined treatment practices and knowledge of smallholder farmers of this
      parasite plus determined annual calf morbidity and mortality and identified
      potential risk factors for these estimates. Interviews were conducted with 273
      smallholder farmers who had calves tested for T. vitulorum 4-6 months earlier.
      Reproductive rates of 0.6 and 0.4 calf per annum in cattle and buffalo
      respectively, and annual calf morbidity and mortality of 42.6% (CI 0.38-0.47) and
      37.3% (CI 0.33-0.42) respectively, were identified. Interviewed farmers had
      either none (80.6%) or only minimal (19.4%) knowledge about T. vitulorum and only
      2.5% of the farmers treated their calves for T. vitulorum using the recommended
      control regime. Multivariable logistic regression analyses with random effects
      showed that the number of adult cattle per household, T. vitulorum infection
      status of the household herd and farmer knowledge of T. vitulorum were
      significantly associated with calf morbidity and mortality. Financial analysis
      using partial budgeting showed a net benefit of USD 3.69, 7.46, 11.09 or 14.86
      per calf when treating calves with pyrantel and attributing 25%, 50%, 75% or 100%
      of morbidity and mortality to T. vitulorum infection. The study identified that
      poor reproduction, high calf morbidity and mortality combined with very limited
      farmer knowledge and effective control of endemic Toxocariasis, contribute to
      suboptimal large ruminant production in mixed smallholder farming systems in
      South-East Asia. The large net benefit per calf achievable by a single pyrantel
      treatment should drive implementation of this intervention by smallholder
      farmers, especially as demand for livestock products continues to increase in
      this region and forces a change to more production oriented farming. To support
      this, continued capacity building that ensures knowledge transfer of best
      practice T. vitulorum control to smallholder farmers is required. 

PMID- 24290496
TI  - Risk factors associated with increased mortality of farmed Pacific oysters in
      Ireland during 2011.
AB  - The Pacific oyster, Crassostrea gigas, plays a significant role in the
      aquaculture industry in Ireland. Episodes of increased mortality in C. gigas have
      been described in many countries, and in Ireland since 2008. The cause of
      mortality events in C. gigas spat and larvae is suspected to be multifactorial,
      with ostreid herpesvirus 1 (OsHV-1, in particular OsHV-1MUvar) considered a
      necessary, but not sufficient, cause. The objectives of the current study were to
      describe mortality events that occurred in C. gigas in Ireland during the summer
      of 2011 and to identify any associated environmental, husbandry and oyster
      endogenous factors. A prospective cohort study was conducted during 2010-2012,
      involving 80 study batches, located at 24 sites within 17 bays. All 17 bays had
      previously tested positive for OsHV-1MUvar. All study farmers were initially
      surveyed to gather relevant data on each study batch, which was then tracked from
      placement in the bay to first grading. The outcome of interest was cumulative
      batch-level mortality (%). Environmental data at high and low mortality sites
      were compared, and a risk factor analysis, using a multiple linear regression
      mixed effects model, was conducted. Cumulative batch mortality ranged from 2% to
      100% (median=16%, interquartile range: 10-34%). The final multivariable risk
      factor model indicated that batches imported from French hatcheries had
      significantly lower mortalities than non-French hatcheries; sites which tested
      negative for OsHV-1MUvar during the study had significantly lower mortalities
      than sites which tested positive and mortalities increased with temperature until
      a peak was reached. There were several differences between the seed stocks from
      French and non-French hatcheries, including prior OsHV-1MUvar exposure and
      ploidy. A range of risk factors relating to farm management were also considered,
      but were not found significant. The relative importance of prior OsHV-1MUvar
      infection and ploidy will become clearer with ongoing selection towards OsHV
      1MUvar resistant oysters. Work is currently underway in Ireland to investigate
      these factors further, by tracking seed from various hatchery sources which were
      put to sea in 2012 under similar husbandry and environmental conditions. 

PMID- 24290497
TI  - Temporal and regional patterns of Smad activation in the rat hippocampus
      following global ischemia.
AB  - In this study, we examined the temporal and regional patterns of Smad activation
      in the rat hippocampus following global ischemia. We also examined the
      association between Smad activation and ischemia-induced pathology in the
      hippocampus. We found that 1) Smad1, -2, -3, and -5 proteins were detected in the
      rat hippocampus by means of western blot and immunohistochemistry; 2) after 5 min
      of ischemia, Smad2 and Smad3 proteins accumulated in the nuclei of pyramidal
      cells in the CA1 region, which is vulnerable to ischemia; 3) after 3 min of
      ischemia, which was non-lethal, there was no such nuclear accumulation of Smad2
      and Smad3 in the CA1 region; 4) following injection of activin A, nuclear
      accumulation of Smad2 and Smad3 was induced not only in pyramidal cells of the
      CA1 region, but also in pyramidal cells of the CA3 region as well as in granule
      cells of the DG region; 5) activin A-induced nuclear accumulation of Smad2 and
      Smad3 neither caused degeneration of hippocampal neurons nor prevented
      degeneration induced by ischemia. These results suggest that in the hippocampus,
      ischemia-induced activation of Smad2 and Smad3 is associated with the response to
      stress but is not related to neuronal survival or death.

PMID- 24290498
TI  - Long-term effects of dalfampridine in patients with multiple sclerosis.
AB  - BACKGROUND/OBJECTIVE: Dalfampridine is the extended-release formulation of 4
      aminopyridine and is approved for the symptomatic treatment of impaired mobility
      in patients with multiple sclerosis. Our aim was to examine the short- and long
      term effects of treatment with dalfampridine on motoric and cognitive assessment
      parameters of multiple sclerosis (MS) patients over 9-12 months. METHODS: Fifty
      two patients with MS with an EDSS between 4.0 and 7.0 and impaired mobility were
      evaluated for parameters of walking ability, MSFC, cognitive and motor fatigue
      and evoked potentials at treatment initiation with dalfampridine as well as 2
      weeks and after 9-12 months later. RESULTS: Thirty out of fifty-two patients
      (~60%) were still on treatment after 9-12 months. Two weeks after treatment
      initiation, significant ameliorations could be found for T25FW, maximum walking
      distance as well as motoric and cognitive fatigue which still persisted after 9
      12 months. In contrast significant effects for velocity were observed only after
      2 weeks, for improvement in PASAT only after 9-12 months. A tendency for
      improvement of somatosensory evoked potentials was found in a subset of patients.
      CONCLUSION: Dalfampridine shows positive short- and long-term effects on motoric
      and cognitive assessment parameters in an open-label observational study in a
      cohort of patients with MS.

PMID- 24290499
TI  - Cauda equina involvement in Susac's syndrome.
AB  - Susac's syndrome is a rare autoimmune microangiopathy characterized by the
      clinical triad of encephalopathy, branch retinal artery occlusions, and
      sensorineural hearing loss. In many cases, the clinical triad is not fully
      present at the onset of symptoms. MRI studies often show characteristic punched
      out lesions of the central fibers of the corpus callosum, and leptomeningeal
      enhancement and deep gray matter lesions may also be seen. Here we present a case
      of Susac's syndrome in a middle aged man with the unique clinical finding of
      cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root
      enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed
      evidence of a pauci-immune endotheliopathy, consistent with pathology described
      in previous cases of Susac's syndrome. This case is important not only because it
      expands the clinical features of Susac's syndrome but also because it clarifies
      the mechanism of a disorder of the endothelium, an important target for many
      disorders of the nervous system. 

PMID- 24290500
TI  - Clinical predictors and outcome of patients of acute stroke requiring ventilatory
      support: a prospective hospital based cohort study.
AB  - The purpose of this study was to identify clinical factors which may help in
      predicting the requirement of support of mechanical ventilation (MV) in patients
      with stroke. This was a prospective cohort study done at a tertiary referral
      center of India, from December 2008 to December 2009. All consecutive patients of
      acute stroke, who were admitted from emergency or through outpatient department,
      and were >= 18 years and in whom written consent was available, were considered
      for the study. Of 193 patients included in the study, 60 (31.08%) patients were
      intubated due to various reasons. Multivariate analysis of statistically
      significant and most clinically important variables showed that overall predictor
      accuracy of requirement of mechanical ventilation is 88% if patients had history
      of progression of symptoms (OR = 10.38; p<0.001), loss of consciousness at the
      time of onset (OR=3.18; p=0.011) and GCS motor score <= 5 (p < OR = 34.62;
      0.001). The findings of this study suggest that factors including the presence of
      poor sensorium, the progression of symptom and low motor GCS are independent
      predictors of requirement of mechanical ventilation in patients with stroke and
      appropriate and cautious timely use of MV can help in improving mortality and
      morbidity from stroke.

PMID- 24290501
TI  - Do you see what I feel?--Electrophysiological correlates of emotional face and
      body perception in schizophrenia.
AB  - OBJECTIVE: We aimed to elucidate whether impaired affective face processing-
      behaviourally and with regard to P100 and N170 components--is paralleled by
      similar deficits in body processing in schizophrenia. Furthermore, we aimed to
      assess modulations by the processing of emotional or personal identity of the
      stimuli. METHODS: Fourteen patients with schizophrenia and 15 healthy controls
      were assessed with a Delayed Matching-to-Sample Task involving variations of the
      emotional (same vs. different valence) and personal identity (same vs. different
      person) of bodies and faces. RESULTS: Patients showed overall poorer behavioural
      performance. In controls, P100 amplitudes were enhanced in the "same
      identity/different emotions" vs. "same identity/same emotion" condition and N170
      amplitudes were larger for different vs. same emotions. In the patients, P100
      amplitudes were enhanced in the right relative to the left hemisphere for faces,
      but not for bodies. CONCLUSIONS: Patients with schizophrenia show deficient
      modulation of the P100 and N170 components by emotional and personal identity of
      faces and bodies, which may relate to deficient context processing. SIGNIFICANCE:
      Our findings suggest for the first time alterations of the electrophysiological
      correlates of body processing in schizophrenia.

PMID- 24290502
TI  - Temporal evolution of event-related desynchronization in acute stroke: a pilot
      study.
AB  - OBJECTIVE: Assessment of event-related desynchronization (ERD) may assist in
      predicting recovery from stroke and rehabilitation, for instance in BCI
      applications. Here, we explore the temporal evolution of ERD during stroke
      recovery. METHODS: Ten stroke patients and eleven healthy controls were recruited
      to participate in a hand movement task while EEG was being recorded. Four
      measurements were conducted in eight patients within four months. We quantified
      changes of ERD using a modulation strength measure, S(m), which represents an
      area and amplitude of ERD. RESULTS: 7/8 patients showed good recovery. Absence-or
      reduction of ipsilesional modulation was initially found in stroke patients but
      not in the healthy controls. In the patient group, two evolutions were found in
      6/8 patients: a significant increase in ipsilesional S(m); and a decreasing trend
      in contralesional S(m). In the only non-recovery patient, absence of ipsilesional
      modulation was observed, while his contralesional S(m) increased with time after
      stroke. CONCLUSION: The two evolutions presumably reflect the reorganization of
      brain networks and functional recovery after acute stroke. The significant
      increase of ipsilesional S(m) in patients with a good recovery suggests an
      important role of this hemisphere during recovery. SIGNIFICANCE: Improved
      understanding of ERD in acute stroke may assist in prognostication and
      rehabilitation.

PMID- 24290504
TI  - 'Physick keeps her very bare': why would anyone see a doctor in the seventeenth
      century?

PMID- 24290503
TI  - Might men diagnosed with metastatic prostate cancer benefit from definitive
      treatment of the primary tumor? A SEER-based study.
AB  - BACKGROUND: Few data exist regarding the impact on survival of definitive
      treatment of the prostate in men diagnosed with metastatic prostate cancer
      (mPCa). OBJECTIVE: To evaluate the survival of men diagnosed with mPCa based on
      definitive treatment of the prostate. DESIGN, SETTING, AND PARTICIPANTS: Men with
      documented stage IV (M1a-c) PCa at diagnosis identified using Surveillance
      Epidemiology and End Results (SEER) (2004-2010) and divided based on definitive
      treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or
      no surgery or radiation therapy (NSR). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Kaplan-Meier methods were used to calculate overall survival (OS).
      Multivariable competing risks regression analysis was used to calculate disease
      specific survival (DSS) probability and identify factors associated with cause
      specific mortality (CSM). RESULTS AND LIMITATIONS: A total of 8185 patients were
      identified: NSR (n=7811), RP (n=245), and BT (n=129). The 5-yr OS and predicted
      DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%,
      respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients
      (22.5% and 48.7%, respectively) (p<0.001). Undergoing RP or BT was each
      independently associated with decreased CSM (p<0.01). Similar results were noted
      regardless of the American Joint Committee on Cancer (AJCC) M stage. Factors
      associated with increased CSM in patients undergoing local therapy included AJCC
      T4 stage, high-grade disease, prostate-specific antigen >=20 ng/ml, age >=70 yr,
      and pelvic lymphadenopathy (p<0.05). The major limitation of this study was the
      lack of variables from SEER known to influence survival of patients with mPCa,
      including treatment with systemic therapy. CONCLUSIONS: Definitive treatment of
      the prostate in men diagnosed with mPCa suggests a survival benefit in this large
      population-based study. These results should serve as a foundation for future
      prospective trials. PATIENT SUMMARY: We used a large population-based cancer
      database to examine survival in men diagnosed with metastatic prostate cancer
      (mPCa) undergoing definitive therapy for the prostate. Local therapy (LT)
      appeared to confer a survival benefit. Therefore, we conclude that prospective
      trials are needed to further evaluate the role of LT in mPCa.

PMID- 24290507
TI  - 'God heals, and the doctor takes the fee': combatting the negative reputation.

PMID- 24290508
TI  - 'A sacred anatomy both of soul and body': Godly physicians in sermon literature.

PMID- 24290509
TI  - 'Medling fops' with their 'gagling goose-quils': the competition.

PMID- 24290510
TI  - 'Every man his own doctor': physicians and the printing boom.

PMID- 24290511
TI  - 'A christian's groans under the body of sin': the pox and the pious physician.

PMID- 24290512
TI  - 'The baneful source of all our woe': women and the pox.

PMID- 24290513
TI  - 'A broom in the hand of the almighty': the plague and the unruly poor.

PMID- 24290514
TI  - Conclusion. The physicians' inroads during the seventeenth century in overcoming
      their issues of status.

PMID- 24290517
TI  - Docosahexaenoic acid inhibited the Wnt/beta-catenin pathway and suppressed breast
      cancer cells in vitro and in vivo.
AB  - N-3 fatty acids (FAs) are essential FAs necessary for human health and are known
      to possess anticancer properties. However, the relationship between n-3 FAs and
      beta-catenin, one of the key components of the Wnt signaling pathway, in mouse
      breast cancer remains poorly characterized. In this study, 4T1 mouse breast
      cancer cells were exposed to a representative n-3 FA, docosahexaenoic acid (DHA),
      to investigate the relationship between n-3 FAs and the Wnt/beta-catenin
      signaling pathway in vivo and in vitro. In vitro studies showed that DHA strongly
      inhibited cell growth, and induced G1 cell cycle arrest both in 4T1 mouse breast
      cells and MCF-7 human breast cells. DHA reduced beta-catenin expression and T
      cell factor/lymphoid-enhancing factor reporter activity in 4T1 mouse breast
      cells. In addition, DHA down-regulated the expression of downstream target genes
      such as c-myc and cyclinD1. In vivo, therapy experiments were conducted on Babl/c
      mice bearing breast cancer. We found that feeding mouse the 5% fish oil
      supplemented diet for 30 days significantly reduced the growth of 4T1 mouse
      breast cancer in vivo through inhibition of cancer cell proliferation as well as
      induction of apoptosis. Feeding animals a 5% fish oil diet significantly induced
      down-regulation of beta-catenin in tumor tissues with a notable increase in
      apoptosis. In addition, fish oil-supplemented diet decreased lung metastases of
      breast cancer. These observations suggested that DHA exerted its anticancer
      activity through down-regulation of Wnt/beta-catenin signaling. Thus, our data
      call for further studies to assess the effectiveness of fish oil as a dietary
      supplement in the prevention and treatment of breast cancer. 

PMID- 24290518
TI  - Historical milestones and progress in the research on alcohol septal ablation for
      hypertrophic obstructive cardiomyopathy.
AB  - The first alcohol septal ablation was performed almost 20 years ago in 1994;
      since then it has become a widely used technique for the treatment of highly
      symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). It has
      been shown that postprocedural basal septal shrinking as a result of myocardial
      scarring is followed by a decrease in left ventricular (LV) obstruction,
      regression of LV hypertrophy within the first postprocedural year, improvement of
      diastolic function, and reduction of the degree of mitral regurgitation. All
      these changes are accompanied by significant symptom relief. Although there is
      only limited evidence of postprocedural long-term survival, all the studies
      presented here are consistent in the low incidence of sudden death and similar
      prognoses with an age- and sex-matched general population. Conversely, we still
      have to be aware that a certain knowledge gap exists with regard to
      postprocedural long-term outcome. Therefore, careful selection of patients for
      alcohol septal ablation is needed, and all patients should be treated in centres
      offering all therapeutic options. 

PMID- 24290519
TI  - Circulating endothelial progenitor cells and in-stent restenosis: friend, foe, or
      none of the above?

PMID- 24290520
TI  - Challenges in the classification of adolescent idiopathic scoliosis and the
      utility of artificial neural networks.

PMID- 24290521
TI  - Regarding the article entitled "The utility of routine postoperative radiographs
      after cervical spine fusion" by Grimm et al. in The Spine Journal 13 (2013,764
      769).

PMID- 24290522
TI  - The utility of routine postoperative radiographs after cervical spine fusion.

PMID- 24290523
TI  - A trauma quality improvement programme associated with improved patient outcomes:
      21 years of experience at an Australian Major Trauma Centre.
AB  - INTRODUCTION: Quality improvement programmes are an important part of care
      delivery in trauma centres. The objective was to describe the effect of a
      comprehensive quality improvement programme on long term patient outcome trends
      at a low volume major trauma centre in Australia. METHODS: All patients aged 15
      years and over with major trauma (Injury Severity Score>15) admitted to a single
      inner city major trauma centre between 1992 and 2012 were studied. The outcomes
      of interest were in-hospital mortality and transfer to rehabilitation. Time
      series analysis using integer valued autoregressive Poisson models was used to
      determine the reduction in adjusted monthly count data associated with the
      intervention period (2007-2012). Risk adjusted odds ratios for mortality over
      three yearly intervals was also obtained using multivariable logistic regression.
      Crude and risk adjusted mortality was compared before and after the
      implementation period. RESULTS: 3856 patients were analysed. Crude in-hospital
      mortality fell from 16% to 10% after implementation (p<0.001). The intervention
      period was associated with a 25% decrease in monthly mortality counts. Risk
      adjusted mortality remained stable from 1992 to 2006 and did not fall until the
      intervention period. Crude and risk adjusted transfer to in-patient
      rehabilitation after major trauma also declined during the intervention period.
      CONCLUSION: In this low volume major trauma centre, the implementation of a
      comprehensive quality improvement programme was associated with a reduction in
      crude and risk adjusted mortality and risk adjusted discharge to rehabilitation
      in severely injured patients.

PMID- 24290524
TI  - Mutations in NSCLC and their link with lung cancer-associated thrombosis: a case
      control study.
AB  - INTRODUCTION: The association of venous thromboembolic events (VTE) and lung
      cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has
      been associated with a worse prognosis and a poor quality of life. Underlying
      cancer biological features such as tumour mutations may contribute to VTE risk
      and cancer prognosis. Since preclinical data suggest a link between thrombosis
      and KRAS mutations in tumours, we aimed to validate this association in a patient
      registry cohort. METHODS: A retrospective case control study was performed using
      the CHUM NSCLC registry. Cases had VTE occurring 6months previous to or after a
      diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and
      migratory superficial thrombophlebitis) was confirmed by a review of the imaging
      reports. Controls were patients with NSCLC without thrombosis matched for age and
      stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for
      KRAS/EGFR mutation analysis or insufficient clinical information. RESULTS:
      Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls
      without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC
      patients are respectively 2.67 (1.12-6.42; p=0.014) and 0.99 (0.27-3.48; p=0.99).
      CONCLUSIONS: KRAS mutation is associated with an increased risk of VTE in this
      NSCLC cohort. These findings are consistent with preclinical studies. Prospective
      data on VTE rates from clinical trials with molecularly defined NSCLC are needed
      to confirm these findings.

PMID- 24290525
TI  - Microparticle bearing tissue factor: a link between promyelocytic cells and
      hypercoagulable state.
AB  - Patients with hematological malignancies have a 28-fold increased risk of venous
      thromboembolism (VTE). Among patients with acute myelogenous leukemia (AML), the
      2-year cumulative incidence of VTE is 5.2%. Several studies suggest that
      microvesicles (MVs) harboring TF may play a role in VTE and disseminated
      intravascular coagulation (DIC) in acute promyelocytic leukemia (APL). The aim of
      this study was to assess the capacity of untreated (APL) cells to shed
      procoagulant MVs. APL cells (NB4 and HL-60 cell lines) and MVs were separated by
      filtration (0.1-0.22-0.45-0.65 MUm). The procoagulant activity (PCA) was assessed
      by thrombin generation assay (TGA). Alternatively, MVs were incubated with anti
      Tissue Factor (TF) antibodies, with annexin V to assess the contribution of TF
      and phospholipids (PL) to the PCA, respectively. NB4 cells had a high PCA mainly
      triggered by MVs of size under 0.45 MUm. The PCA of MVs was related to the
      expression of active TF and PL. HL-60 cells had a weaker PCA since TF is mostly
      present in its inactive form. Moreover, HL-60 do not produce MVs<0.65 MUm
      associated with PCA. MVs could have a predicting value for VTE and DIC in
      patients with acute promyelocytic leukemia and could inform physicians about the
      optimal use of a thromboprophylaxis.

PMID- 24290526
TI  - Complexity-loss in fetal heart rate dynamics during labor as a potential
      biomarker of acidemia.
AB  - BACKGROUND: Continuous fetal heart rate (FHR) monitoring remains central to
      intrapartum care. However, advances in signal analysis are needed to increase its
      accuracy in diagnosis of fetal hypoxia. AIMS: To determine whether FHR
      complexity, an index of multiscale variability, is lower among fetuses born with
      low (<=7.05) versus higher pH values, and whether this measure can potentially be
      used to help discriminate the two groups. STUDY DESIGN: Evaluation of a pre
      existing database of sequentially acquired intrapartum FHR signals. SUBJECTS: FHR
      tracings, obtained from a continuous scalp electrocardiogram during labor, were
      analyzed using the multiscale entropy (MSE) method in 148 singletons divided in
      two groups according to umbilical artery pH at birth: 141 fetuses with pH>7.05
      and 7 with pH<=7.05. A complexity index derived from MSE analysis was calculated
      for each recording. RESULTS: The complexity of FHR signals for the last two hours
      before delivery was significantly (p<0.004) higher for non-acidemic than for
      acidemic fetuses. The difference between the two groups remained significant
      (p<0.003) when FHR data from the last 30min before delivery were excluded.
      CONCLUSION: Complexity of FHR signals, as measured by the MSE method, was
      significantly lower for acidemic than non-acidemic fetuses. These results are
      consistent with previous studies showing that decreased nonlinear complexity is a
      dynamical signature of disrupted physiologic control systems. This analytic
      approach may have discriminative value in FHR analysis.

PMID- 24290527
TI  - Growth factors and gastrointestinal anastomotic healing.
AB  - BACKGROUND: Failure of anastomotic healing in the gastrointestinal tract is a
      major source of surgery-related morbidity, repeated surgical procedures, and
      impaired quality of life. Growth factors have been shown to be involved in
      healing processes in various tissues including the gastrointestinal tract. This
      opens the perspective to use growth factors therapeutically to support impaired
      anastomotic healing. The aim of the present study was to review the particular
      role of several growth factors in different phases of anastomotic healing,
      experimental approaches of growth factor application, and to discuss
      possibilities and limitations of growth factor-directed interventions in
      gastrointestinal surgery. MATERIALS AND METHODS: A PubMed search was performed to
      examine the potential role of fibroblast growth factor, epidermal growth factor,
      heparin binding EGF-like growth factor, transforming growth factor beta, insulin
      like growth factor I, vascular endothelial growth factor, and platelet-derived
      growth factor during anastomotic healing. RESULTS: Growth factors show beneficial
      effects on a broad range of cell types and regulate various processes during all
      phases of tissue healing. Despite extensive research in the field of growth
      factors, additional evidence is needed before translating into a clinical
      setting. CONCLUSIONS: Future research should focus on adequate sustained but
      limited drug delivery. Undesired side effects, such as formation of strictures,
      development of peritoneal adhesions, and potential induction of malignancies,
      have to be reflected. Although growth factor application is currently far from
      clinical routine in gastrointestinal surgery, it might find application in
      selected patients at risk for impaired anastomotic healing, such as patients with
      long-time steroid therapy, immunosuppressives, inflammatory disorders, sepsis,
      hemodynamic shock, malnutrition, or neoadjuvant radiochemotherapy.

PMID- 24290528
TI  - Optimising sample collection for placental research.
AB  - Biobanks provide an important repository of samples for research purposes.
      However, for those samples to reflect the in vivo state, and for experimental
      reliability and reproducibility, careful attention to collection, processing and
      storage is essential. This is particularly true for the placenta, which is
      potentially subjected to stressful conditions during delivery, and sample
      collection may be delayed owing to routine postpartum inspection by clinical
      staff. In addition, standardisation of the collection procedure enables samples
      to be shared among research groups, allowing larger datasets to be established.
      Here, we provide an evidence-based and experts' review of the factors surrounding
      collection that may influence data obtained from the human placenta. We outline
      particular requirements for specific techniques, and propose a protocol for
      optimal sample collection. We recognise that the relevance of these factors, and
      of the sample types collected to a particular study will depend on the research
      questions being addressed. We therefore anticipate that researchers will select
      from the protocol to meet their needs and resources available. Wherever possible,
      we encourage researchers to extend their collection to include additional samples
      that can be shared on an international collaborative basis, with appropriate
      informed consent, to raise the quality, as well as quantity, of placental
      research. 

PMID- 24290530
TI  - An examination of ESI triage scoring accuracy in relationship to ED nursing
      attitudes and experience.
AB  - INTRODUCTION: This research was designed to examine if there is a difference in
      nurse attitudes and experience for those who assign Emergency Severity Index
      (ESI) scores accurately and those who do not assign ESI scores accurately.
      Studies that have used ESI scoring discussed the role of experience, but have not
      specifically addressed how the amount of experience and attitude towards patients
      in triage affect the triage nurse's decision-making capabilities. METHODS: A
      descriptive, exploratory study design was used. Data from 64 nurses and 1,644
      triage events at 3 emergency departments was collected. Participants completed
      demographic data, attitude (Caring Nurse Patient Interaction, CNPI-23) survey,
      and triage data collection tools during the continuous 8-hour triage shift.
      Clinical nurse expert raters retrospectively reviewed the charts and assigned an
      ESI score to be compared with the nurse. Descriptive statistics were used to
      describe the nurse and Pearson's correlation was used to examine the relationship
      between experience and attitude. RESULTS: In this study of 64 nurse participants,
      the ESI score assigned by nurse participants did not differ significantly based
      on years of experience or CNPI mean score. The Kappa statistic ranged from a high
      of 0.63 in the nurse participant with 1.00 to 1.99 years of experience to a low
      of 0.51 in the nurse participant with 15 to 19 years of experience. The nurse
      participants with an overall mean CNPI-23 score of 106 to 115 achieved the
      highest agreement compared with a single participant with a CNPI-23 overall mean
      score of less than 77 who had a Kappa agreement of 0.50. The nurse participants
      with a CNPI-23 overall mean score between 81 and 92 demonstrated agreement of
      0.54 to 0.60. DISCUSSION: Based on the high level of liability the triage area
      presents, special consideration needs to be made when deciding which nurse should
      be assigned to that area. The evidence produced from this study should provide
      some reassurance to ED managers and nurses alike that nurses with minimal ED
      experience and a working understanding of the ESI 5-level triage algorithm
      possess the knowledge and the capacity to safely and appropriately triage
      patients in the emergency department.

PMID- 24290531
TI  - Genetically modified mice related to schizophrenia and other psychoses: seeking
      phenotypic insights into the pathobiology and treatment of negative symptoms.
AB  - Modelling negative symptoms in any animal model, particularly in mice mutant for
      genes related to schizophrenia, is complicated by the absence of the following
      key elements that might assist in developing validation criteria: clinical
      clarity surrounding this symptom constellation; any clear association between
      negative symptoms and pathological signature(s) in the brain; and therapeutic
      strategies with material clinical efficacy against these symptoms. In this
      review, the application of mutant mouse models to the study of negative symptoms
      is subjected to critical evaluation, focussing on the following challenges: (a)
      conceptual issues relating to negative symptoms and their evaluation in mutant
      models; (b) measurement of negative symptoms in mice, in terms of social
      behaviour, motivational deficits/avolition and anhedonia; (c) studies in mutants
      with disruption of genes either regulating aspects of neurotransmission
      implicated in schizophrenia or associated with risk for psychotic illness; (d)
      the disaggregation of behavioural phenotypes into underlying pathobiological
      processes, as a key to the development of new therapeutic strategies for negative
      symptoms. Advances in genetic and molecular technologies are facilitating these
      processes, such that more accurate models of putative schizophrenia-linked
      genetic abnormalities are becoming feasible. This progress in terms of mimicking
      the genetic contribution to distinct domains of psychopathology associated with
      psychotic illness must be matched by advances in conceptual/clinical relevance
      and sensitivity/specificity of phenotypic assessments at the level of behaviour. 

PMID- 24290532
TI  - How well do randomized controlled trial data generalize to 'real-world' clinical
      practice settings? A comparison of two generalized anxiety disorder studies.
AB  - The aim of this post-hoc comparison is to compare efficacy and tolerability
      results from two generalized anxiety disorder (GAD) studies: a placebo
      controlled, randomized controlled trial (RCT) and a study conducted in the
      clinical practice setting, and to evaluate the extent to which results from RCTs
      in GAD patients can be generalized to clinical practice. In the clinical practice
      study, GAD outpatients (n=578) were treated with 4 weeks of pregabalin 150
      600mg/day. In the double-blind placebo-controlled RCT, GAD outpatients (n=249)
      were randomized to 8 weeks of pregabalin (300-600mg/day), or placebo (only the
      first 4 weeks are included in the current analysis). Efficacy measures included
      the Hospital Anxiety and Depression Scale - Anxiety and Depression subscales
      (HADS-A; HADS-D), a visual analogue anxiety scale (VAS-Anxiety), and the Medical
      Outcomes Study Sleep Problems Index (MOS-SPI). Baseline HADS-A and HADS-D scores
      were both higher in the clinical practice study vs. the RCT. In the RCT,
      treatment with pregabalin resulted in significantly greater Week 4 change vs.
      placebo in the HADS-A (-5.3 vs. -3.9; P<0.005), VAS-Anxiety (-24.0 vs. -13.3;
      P<0.02), MOS-SPI (-19.1 vs. -9.5; P<0.01), and HADS-D (-2.7 vs. -1.4; P<0.05).
      The magnitude of Week 4 improvement on pregabalin in the clinical practice study
      was numerically larger on the HADS-A (-5.9), VAS-Anxiety (-36.0), MOS-SPI (
      22.7), and HADS-D (-5.1), despite use of lower doses. These results suggest that
      clinical practice patients with GAD may achieve comparable efficacy on lower
      doses of pregabalin than tested in RCTs, despite having comparable levels of
      anxiety symptom severity at baseline. The current exploratory comparison also
      suggests that results from RCTs in patients with GAD may not be directly
      generalizable to clinical practice. 

PMID- 24290533
TI  - Monte Carlo dosimetry for the Papillon P50 contact radiotherapy and IORT device.
AB  - Contact radiotherapy uses small field sizes and very short SSDs to deliver low
      energy X-rays very close to the position of a tumour. We present a Monte Carlo
      simulation of the Papillon contact radiotherapy machine, and in particular the
      backscatter factor, to investigate whether the factors given in current Codes of
      practice for kV dosimetry remain valid under these conditions. 

PMID- 24290534
TI  - MiR-210: A potential therapeutic target against radiation-induced enteropathy.
AB  - A previously undescribed and robust miR210 overexpression is shown in intestinal
      samples obtained from patients with radiation enteropathy and fibrotic cultured
      cells. In addition, miR-210 overexpression is repressed by antifibrotic treatment
      combining pentoxifylline and alpha-tocopherol.

PMID- 24290535
TI  - Understanding the impact of the treatment pathway upon the health-related quality
      of life of women with newly diagnosed endometrial cancer - a qualitative study.
AB  - PURPOSE: (1) To determine the impact of treatment and recovery on the health
      related quality of life (HRQoL) of endometrial cancer (EC) patients. (2) To
      explore how treatment types and delivery affect HRQoL and invite suggestions for
      improvement. METHODS: Qualitative study. In-depth, semi-structured interviews at
      3, 6, 9 or 12 months post-treatment were carried out with 22 women with stage IA
      to IVB EC who had undergone treatment at a tertiary referral centre for
      gynaecological cancers in Sheffield, UK. 21 were treated surgically and 4
      received adjuvant treatment. Data were analysed using an inductive thematic
      approach. RESULTS: Four dominant themes emerged regarding the treatment pathway:
      pre-treatment concerns, experience during treatment, post-treatment and
      survivorship issues. Expectations and understandings of EC and its treatment were
      often inaccurate. Proper explanations eased anxiety but were uncommon.
      Laparoscopic surgery was welcomed where offered but did not necessarily influence
      coping ability. Instead, women evaluated treatment impacts against their
      expectations. Treatments affected women's physical abilities, self-perception and
      relationships resulting in re-evaluation of lifestyle. CONCLUSIONS: The impact of
      treatment upon HRQoL for women with EC differs from other gynaecological cancers.
      Better information provision would enhance coping ability. Coping methods and
      expectations appear to influence HRQoL more than treatment modality.

PMID- 24290536
TI  - On the ASR and ASR thermal residues characterization of full scale treatment
      plant.
AB  - In order to obtain 85% recycling, several procedures on Automotive Shredder
      Residue (ASR) could be implemented, such as advanced metal and polymer recovery,
      mechanical recycling, pyrolysis, the direct use of ASR in the cement industry,
      and/or the direct use of ASR as a secondary raw material. However, many of these
      recovery options appear to be limited, due to the possible low acceptability of
      ASR based products on the market. The recovery of bottom ash and slag after an
      ASR thermal treatment is an option that is not usually considered in most
      countries (e.g. Italy) due to the excessive amount of contaminants, especially
      metals. The purpose of this paper is to provide information on the
      characteristics of ASR and its full-scale incineration residues. Experiments have
      been carried out, in two different experimental campaigns, in a full-scale tyre
      incineration plant specifically modified to treat ASR waste. Detailed analysis of
      ASR samples and combustion residues were carried out and compared with literature
      data. On the basis of the analytical results, the slag and bottom ash from the
      combustion process have been classified as non-hazardous wastes, according to the
      EU waste acceptance criteria (WAC), and therefore after further tests could be
      used in future in the construction industry. It has also been concluded that ASR
      bottom ash (EWC - European Waste Catalogue - code 19 01 12) could be landfilled
      in SNRHW (stabilized non-reactive hazardous waste) cells or used as raw material
      for road construction, with or without further treatment for the removal of heavy
      metals. In the case of fly ash from boiler or Air Pollution Control (APC)
      residues, it has been found that the Cd, Pb and Zn concentrations exceeded
      regulatory leaching test limits therefore their removal, or a stabilization
      process, would be essential prior to landfilling the use of these residues as
      construction material. 

PMID- 24290537
TI  - Biopsychosocial correlates of persistent postsurgical pain in women with
      endometriosis.
AB  - OBJECTIVE: To examine pain and biopsychosocial correlates over time for women
      with persistent postsurgical pain after surgery for endometriosis. METHODS: Cross
      sectional study of women who underwent any endometriosis surgery between 2003 and
      2006. Following surgery, patients completed validated questionnaires (Short-Form
      McGill Pain Questionnaire, 12-item Short-Form Health Survey, Beck Depression
      Inventory, Coping Strategies Questionnaire catastrophizing subscale). The primary
      outcome was pelvic pain intensity, measured by the McGill total pain score.
      Bivariate comparisons between each potential predictor and pain intensity were
      performed using the chi(2) and t tests, 1-way analysis of variance, and simple
      linear regression. RESULTS: In total, 79 completed the questionnaires and were
      included in the present analysis. The McGill affective pain score was negatively
      correlated with age (beta-coefficient -0.12, P=0.002) and positively correlated
      with catastrophization (beta-coefficient 0.66, P=0.01). Women with a history of
      dyspareunia scored significantly higher on the McGill total pain score (P<0.001);
      there was no association between pain intensity and endometriosis severity.
      CONCLUSION: Younger age and catastrophization are correlated with persistent pain
      following surgery for endometriosis. The severity of endometriosis does not
      predict persistent pain. Further evaluation of psychosocial factors may identify
      patients who are least likely to benefit from surgeries for endometriosis
      associated pelvic pain.

PMID- 24290538
TI  - A comparison of psychological stress among women with and without reproductive
      failure.
AB  - OBJECTIVE: To determine whether women with recurrent implantation failure (RIF)
      after in vitro fertilization (IVF), similar to women with recurrent pregnancy
      loss, have significantly higher stress levels than women without reproductive
      failure, and to compare stress levels between women with RIF and women with
      recurrent pregnancy loss. METHODS: In a questionnaire-based study between
      September 2009 and January 2011, psychological stress was measured among patients
      attending recurrent pregnancy loss and RIF clinics at the Royal Hallamshire
      Hospital, Sheffield, UK. Participants completed the Fertility Problem Inventory
      (FPI), the Perceived Stress Scale (PSS), and the Positive and Negative Affect
      Schedule (PANAS) on their first visit to their respective clinic. Thirty fertile
      control women also completed the 3 validated questionnaires. RESULTS: Compared
      with the control group, women with RIF and recurrent pregnancy loss had
      significantly higher scores in the FPI (RIF, P<0.001; recurrent pregnancy loss,
      P=0.003) and the PANAS negative affect domain (RIF, P=0.004; recurrent pregnancy
      loss, P=0.001), and lower scores in the PANAS positive affect domain (RIF,
      P<0.001; recurrent pregnancy loss, P<0.001). Whereas the perceived stress score
      (PSS) of the recurrent pregnancy loss group was significantly higher than that of
      the control group (P=0.006), the score of the RIF group was not, although the
      difference tended toward statistical significance (P=0.058). CONCLUSION: The
      study findings confirm the stressful nature of RIF and recurrent pregnancy loss.

PMID- 24290539
TI  - Differences in scapular kinematics and scapulohumeral rhythm during elevation and
      lowering of the arm between typical children and healthy adults.
AB  - Scapular kinematics in healthy adults is well described in the literature but
      little is known on typical children. This study aimed to compare the three
      dimensional (3-D) scapular kinematics and scapulohumeral rhythm during the
      elevation and lowering of the arm in the scapular plane in typical children and
      healthy adults. Twenty-six healthy adults (35.34+/-11.65 years, 1.70+/-0.10m,
      70.00+/-12.30kg) and 33 typical children (9.12+/-1.51 years, 1.40+/-0.10m,
      35.40+/-10.45kg) participated in this study. 3-D scapular kinematics were
      obtained using an electromagnetic tracking device. The subjects were asked to
      elevate and lower their arm in the scapular plane. Children showed less scapular
      protraction compared to adults at 120 degrees  during arm elevation, more
      anterior tilt than adults in the elevation and also at 60 degrees , 90 degrees 
      and 120 degrees  during lowering of the arm. Children also showed higher
      scapulohumeral rhythm during lowering of the arm compared to adults from 90
      degrees  to 60 degrees . It was also found a low to little correlation between
      scapular position and age. The study showed small but significant differences in
      scapular kinematics and scapulohumeral rhythm between children and adults. These
      results can help clinicians to improve diagnosis and treatment protocols directed
      to children with dysfunction, as reference values on scapular kinematics in
      healthy children are also provided in this study.

PMID- 24290541
TI  - Effect of shortening the etching time on bonding to sound and caries-affected
      dentin of primary teeth.
AB  - PURPOSE: This study aimed to evaluate the influence of shortening the etching
      time on bonding of an etch-and-rinse and a 2-step self-etch adhesive systems to
      sound dentin (SD) and caries-affected primary tooth dentin (CAD). METHODS: Flat
      dentin surfaces from 48 primary molars were assigned to eight groups, according
      to substrate (SD and CAD- pH-cycling for 14 days), adhesive (Adper Single Bond 2
      [SB] and Clearfil SE Bond [CSEB]), and etching time (recommend by manufacturers
      and reduced by 50 percent). After 24-hour water storage, bonded sticks with cross
      sectional area of 0.8 mm 2 were tested for microtensile bond strength (MUTBS).
      Additionally, two teeth per group were prepared to assess interface morphology
      via scanning electron microscope. The MUTBS means were analyzed by ANOVA and
      Tukey's tests (P<.05). RESULTS: The etching time did not influence the MUTBS to
      SD and CAD. No difference in bonding was observed between adhesives. However, the
      MUTBS values obtained for CAD were lower vs. SD. The etching time interfered in
      hybrid layer thickness only for SB. Thinner hybrid layers were produced when the
      primary tooth dentin was acid etched for half the time. CONCLUSION: Shortening
      the etching time does not jeopardize the bonding to sound and caries-affected
      dentin of primary teeth.

PMID- 24290540
TI  - The effect of fatigued internal rotator and external rotator muscles of the
      shoulder on the shoulder position sense.
AB  - The purpose of this study was to investigate which muscle group, the agonist or
      antagonist, contributes most to the shoulder position sense (SPS). The SPS was
      tested under 2 conditions: fatigued shoulder internal rotator (IR) muscles
      (pectoralis major and latissimus dorsi) and fatigued external rotator (ER)
      muscles (infraspinatus). In each condition, the SPS was measured before and after
      a fatiguing task involving the IR or ER muscles by repeating shoulder joint
      rotation. SPS was measured using a method in which subjects reproduced a
      memorized shoulder joint rotation angle. The position error values in all
      conditions (fatigued IR and ER muscles) and measurement periods (before- and
      after-fatigue task) were compared using 2-way analysis of variance with repeated
      measures (IR/ER*before/after). Position error increased significantly after both
      fatigue tasks (before- vs. after-fatigue: IR muscle, 2.68 degrees  vs. 4.19
      degrees ; ER muscle, 2.32 degrees  vs. 4.05 degrees ). In other words, SPS
      accuracy decreased when either the agonist or antagonist muscle was fatigued.
      This finding indicated that SPS may be affected by an integrated information of
      the afferent signals in the agonist and antagonist muscles. 

PMID- 24290542
TI  - Early mixed dentition treatment of bilateral impaction of permanent mandibular
      first molars.
AB  - Available scientific literature is scarce in covering cases involving impaction
      of permanent mandibular first molars treated in mixed dentition patients. The
      purpose of this report was to present the case of a 7-year-old patient with
      bilateral impaction of permanent mandibular first molars treated early using a
      simple and effective removable appliance. The proposed intervention involved the
      construction of a removable acrylic appliance with bilateral titanium-molybdenum
      alloy distalizing springs to disimpact and allow complete eruption of the molars.
      A button was bonded to the occlusal surface of each molar to be used as a
      leverage point for the distalizing springs. Following seven months of treatment,
      both the permanent mandibular right and left first molars were upright and in
      physiologic position. This case demonstrates that, when this problem is
      identified and treated early, pediatric dentists have the opportunity to minimize
      the complexity of future orthodontic treatment and limit the extent of
      malocclusion in the permanent dentition. 

PMID- 24290543
TI  - Guideline on periodicity of examination, preventive dental services, anticipatory
      guidance/counseling, and oral treatment for infants, children, and adolescents.

PMID- 24290544
TI  - Guideline on caries-risk assessment and management for infants, children, and
      adolescents.

PMID- 24290545
TI  - Guideline on fluoride therapy.

PMID- 24290546
TI  - Guideline on protective stabilization for pediatric dental patients.

PMID- 24290547
TI  - Guideline on use of nitrous oxide for pediatric dental patients.

PMID- 24290548
TI  - Guideline on dental management of heritable dental developmental anomalies.

PMID- 24290549
TI  - Guideline on dental management of pediatric patients receiving chemotherapy,
      hematopoietic cell transplantation, and/or radiation.

PMID- 24290550
TI  - AAPD Clinical Practice Guidelines--why they are more important than ever.

PMID- 24290551
TI  - Maxillary canine-to-maxillary incisor transposition.
AB  - Dental transposition is the positional interchange of two adjacent teeth. Canine
      transpositions are usually accompanied by other dental anomalies, such as:
      impaction of the incisors; missing teeth; peg-shaped lateral incisors; severe
      rotation or malposition of adjacent teeth; dilacerations; and malformations.
      Local pathologic processes, such as tumors, cysts, retained primary canines, and
      supernumerary teeth, might be responsible for canine transposition. The purpose
      of this paper was to present a rare case of maxillary canine-to-maxillary incisor
      transposition in an 8-year-old girl. The patient presented with noneruption of
      the permanent maxillary left central incisor, and a radiographic examination
      revealed an impacted dilacerated incisor. The central incisor was extracted
      because the root was severely dilacerated. At the 3-year follow-up, an oral
      examination revealed that the canine had transposed to the extraction site.
      Through orthodontic traction, combined with reshaping of the tooth, the
      transposed canine was successfully positioned into the incisor position. 

PMID- 24290552
TI  - Antibacterial activity, fluoride release, and physical properties of an
      antibiotic-modified glass ionomer cement.
AB  - PURPOSE: This study's purpose was to examine the influence of adding an
      antibiotic mixture to conventional glass ionomer cement (GIC) on its
      antibacterial activity, fluoride-releasing ability, and physical properties.
      METHODS: An antibiotic mixture containing ciprofloxacin and metronidazole was
      added to GIC at concentration ratios of one percent weight antibiotic/weight
      total powder before mixing (w/w; Group 1) and two percent w/w (Group 2) to obtain
      the test groups. Conventional GIC served as the control. The antibacterial
      activity of the cement specimens was evaluated against Streptococcus mutans and
      Lactobacillus casei using the agar inhibition test. The fluoride release from the
      cement specimens was evaluated using a fluoride ion selective electrode. The
      physical parameters evaluated were net setting time, compressive strength, shear
      bond strength, and microleakage. RESULTS: Group 2 showed a significantly greater
      inhibition zone than Group 1 against both tested organisms, while the control did
      not inhibit organism growth. The addition of antibiotics at one percent and two
      percent to GIC enhanced its fluoride release. At two percent, however, the
      physical properties of GIC were adversely affected. CONCLUSION: Antibiotics at
      one percent weight solute/weight total solution after mixing may modestly confer
      an antibacterial activity to glass ionomer cement and enhance its fluoride
      releasing ability. Its effects on shear bond strength and microleakage were found
      to be encouraging.

PMID- 24290553
TI  - Effects of glass ionomer temporary restorations on pulpal diagnosis and treatment
      outcomes in primary molars.
AB  - PURPOSE: To evaluate 1) if glass ionomer interim temporary restorations (ITR)
      placed for 1-3 months prior to vital pulp therapy (VPT) improved accuracy of
      diagnosing the pulp's clinical status and subsequent VPT success, and 2) the
      effect of the location of the carious lesion on VPT. METHODS: Primary molars
      (N=117) receiving pulp therapy with or without ITR were evaluated
      retrospectively. All teeth had caries extending >50 percent into dentin; caries
      lesion location was identified (proximal or non-proximal). Two examiners rated
      pulp status assessment, caries location, and pulp treatment, and correlated
      treatment outcomes after a mean of 34.7 months to these factors. RESULTS: VPT
      failed more often in first primary molars (P<.001) than in second primary molars.
      Using ITR improved diagnosis of the pulp status, clinical success of VPT,
      (P=.013) and first molar VPT success (P=.02). First primary molars had more
      proximal lesions than second molars (P<.001). Failure of VPT was greater for
      teeth with proximal lesions (P=.03). Use of ITR significantly improved VPT in
      teeth with proximal lesions (P=.007) but not non-proximal lesions (P=.38).
      CONCLUSIONS: ITR placed prior to VPT improved pulpal diagnosis and VPT outcomes.
      Vital pulp therapy was less successful in primary molars with proximal lesions,
      and ITR significantly improved the success.

PMID- 24290554
TI  - The use of local anesthesia during dental rehabilitations: a survey of AAPD
      members.
AB  - PURPOSE: The purpose of this study was to document current practices among
      pediatric and general dentists who are members of the American Academy of
      Pediatric Dentistry (AAPD) regarding the use of local anesthesia (LA) on children
      undergoing dental rehabilitation under general anesthesia (GA). METHODS: A survey
      was administered via e-mail to AAPD members to document the use of LA during
      dental rehabilitations under GA and the rationales for its use. RESULTS: A total
      of 952 of 5,599 members responded to this survey; 79 percent of respondents use
      LA at least part of the time during dental rehabilitations under GA. "Improved
      patient recovery" was the most commonly cited rationale for administering LA.
      Extraction of permanent and primary teeth were the two most common procedures
      cited for the use of LA, respectively. CONCLUSION: There is no consensus among
      the respondents on the use of local anesthesia during dental rehabilitation under
      general anesthesia, but the majority responded that it does play a role in their
      perioperative patient management.

PMID- 24290555
TI  - Root resorption patterns of primary mandibular molars and location of the
      premolar successors: a radiographic evaluation.
AB  - PURPOSE: The purpose of this study was to investigate root resorption patterns of
      primary mandibular molars and to describe the premolar successors' location
      throughout the resorption. METHODS: A total of 271 radiographs of primary
      mandibular molars (56 first molars and 171 second molars) of 187 5- to 12-year
      old patients were reviewed, and the patterns of root resorption and the
      premolars' location were evaluated. RESULTS: In the primary first molar,
      approximately 55 percent of the root resorption occurred in the distal root, and
      41 percent of the root resorption was symmetrical. In the primary second molar,
      approximately 56 percent of the root resorption was symmetrical, and 36 percent
      was in the distal root. More mesial root resorption (~71 percent) occurred when
      the second premolar was mesial. CONCLUSIONS: Primary mandibular first molars
      begin to resorb at seven years old. The premolars' location between the primary
      roots is associated with root resorption. Distal root resorption should be
      expected when caries is present in the distal aspect of a primary second molar.

PMID- 24290556
TI  - Oral health literacy: awareness and practices among pediatric dentists.
AB  - PURPOSE: The purpose of this study was to examine pediatric dentists' awareness
      and experiences with oral health literacy and to identify communication
      techniques used with parents. METHODS: Active North American members of the
      American Academy of Pediatric Dentistry were invited to participate in the
      survey. Descriptive statistical analyses were completed, and Pearson's chi-square
      crosstabs tests were used to compare categorical data between groups. RESULTS:
      Data were collected from 22 percent (N=1,059) of pediatric dentists; 68 to 87
      percent use basic communication techniques routinely, while 36 to 79 percent
      routinely use enhanced communication techniques. Approximately 59 percent (N=620)
      reported having had an experience with health literacy miscommunication, while 11
      percent (N=116) are aware of an error in patient care that resulted from oral
      health literacy miscommunication. Respondents who have had an experience with
      miscommunication were significantly more likely statistically to perceive
      barriers to effective communication as more significant than those without a
      history of miscommunication experience (P<.001). CONCLUSIONS: Most pediatric
      dentists have experienced situations in which a parent has misunderstood
      information. Basic communication techniques were most commonly used, while
      enhanced communication techniques were used less routinely. Those who have had
      experience with oral health literacy miscommunication events perceive barriers to
      effective communication as more significant.

PMID- 24290557
TI  - The experience of medical clinicians implementing fluoride varnish in
      Connecticut.
AB  - PURPOSE: The purpose of this study was to evaluate the success and barriers
      encountered by Connecticut medical clinicians providing and billing for infant
      oral health screenings and fluoride varnish. METHODS: Clinicians trained and
      registered in providing oral health services were surveyed about practice
      demographics, training effectiveness, and implementation barriers. RESULTS: Fifty
      seven of 156 surveys (37 percent) were returned and analyzed. Most respondents
      were female (61 percent), worked at least 10 years (74 percent), and had at least
      25 percent of their patients on Medicaid (79 percent). Respondents varied in how
      prepared they felt to offer services (P<.00). Sixty percent felt "well prepared"
      to provide oral screenings vs. 40 percent and 39 percent for fluoride varnish and
      billing services, respectively. Only 30 percent of respondents provided fluoride
      varnish. Clinicians were more likely to provide fluoride varnish and bill for the
      services if they felt well prepared after the training (P<.00). Referrals for an
      age one dental visit were not routine; 23 percent of clinicians did not refer,
      and 50 percent reported barriers. CONCLUSIONS: Few trained and registered
      clinicians provide fluoride varnish and bill for oral health services, despite
      feeling prepared to provide them. Additional support is required to help medical
      clinicians provide oral health services more consistently.

PMID- 24290558
TI  - Implants in children with hypohidrotic ectodermal dysplasia: an alternative
      approach to esthetic management: case report and review of the literature.
AB  - Ectodermal dysplasia (ED) is a rare congenital disease that affects several
      ectodermal structures. Children with ED may have various manifestations of the
      disease that differ in severity. In addition to its other symptoms, ED causes
      anadontia and hypodontia of the primary or permanent teeth, impacted teeth,
      malformed and widely spaced peg-shaped teeth, and underdeveloped alveolar ridges.
      Since the oral rehabilitation of these cases is often difficult, particularly in
      pediatric patients, treatment should be provided by a multidisciplinary team.
      Dental implants are the treatment of choice when growth has stabilized, and
      implants can be used to support, retain, and stabilize the prosthesis. The
      purpose of this paper was to present a case report of implant placement in a 7
      year-old girl with hypohidrotic ectodermal dysplasia and review the current
      literature to discuss the use of dental implants in such patients. 

PMID- 24290559
TI  - A unique case of craniopagus twins: considerations and challenges for dental
      rehabilitation.
AB  - The purpose of this case report was to describe oral findings and outline
      challenges and considerations for general anesthetic (GA) and dental management
      of 4-year-old female craniopagus (cranially conjoined) twins, at high risk for
      medical comorbidity, who presented for treatment of severe early childhood
      caries. This hospital-based procedure required good interdisciplinary
      communication, cooperation, and presurgical planning to address unique challenges
      and ensure positive postoperative outcomes. Two separate anesthesia teams
      delivered GA simultaneously to each twin. To minimize anesthetic exposure, two
      pediatric dental teams completed dental care concurrently. Extensive plaque
      accumulation and unusual "mirror-image" caries distribution were attributed to
      frequency and postural pooling during feeding. The rehabilitation objective was
      to provide definitive dental management, minimizing future need for dental
      retreatment under GA. Two-month follow-up revealed intact dental restorations,
      good oral hygiene, and weight gain. For these unique twins however, the challenge
      of long-term oral health maintenance remains. 

PMID- 24290560
TI  - Analysis of InsureKidsNow.gov dental providers in New York State.
AB  - PURPOSE: Study purposes were to: (1) validate information of New York State (NYS)
      pediatric dental Medicaid/CHIP providers registered on InsureKidsNow.gov (IKN);
      and (2) compare dental access to available IKN pediatric dental Medicaid provider
      locations by NYS region and population density of young children in poverty
      Methods: Information on 4,634 dental provider locations was obtained by
      collapsing 21,921 listings; 160 locations were randomly telephoned to verify
      consistency and provision of pediatric restorative treatment. Dental provider
      locations to poor child population ratios were compared. RESULTS: Over 90 percent
      of locations were in less than a third of NYS counties. New York City/Long Island
      locations had 5.68 higher odds of accepting new pediatric patients compared to
      locations in the rest of NYS. Of phone numbers called, 22 percent were invalid.
      Nearly 40 percent of valid calls were inconsistent with IKN. Over 90 percent of
      counties had at least one IKN dentist. The median child-in-poverty to provider
      ratio was 85:1. CONCLUSIONS: Improved oversight of InsureKidsNow.gov is required
      to ensure validity and usefulness. Research on the quantity and type of child
      Medicaid/CHIP dental procedures in private practice is needed to accurately
      assess dental access.

PMID- 24290561
TI  - Gingival evaluation of the pediatric cardiac patient.
AB  - PURPOSE: Children with congenital cardiovascular diseases (CCDs) who suffer from
      dental diseases have an increased risk of infective endocarditis. In the light of
      recent evidence, oral inflammatory diseases may also increase the severity of
      their cardiovascular condition. The purpose of this study was to evaluate the
      gingival status of children with congenital cardiovascular diseases in comparison
      to healthy children. METHODS: Fifty 7- to 13-year-old children were included. The
      test group comprised 25 CCD children subdivided into three groups: (1) unrepaired
      ventricular septal defect; (2) aortic valve stenosis; and (3) coarctation of the
      aorta. The control group consisted of 25 healthy age- and gender-matched
      children. Gingivitis, plaque, calculus, and recession were measured on six sites
      per tooth on 12 teeth. RESULTS: CCD children had significantly more gingivitis
      (P<.001), plaque (P<.001), recession (P>.02), and calculus (P<.001) than
      controls. Among the CCDs groups, no statistically significant differences were
      found for gingivitis, plaque, or recession. CONCLUSIONS: Children with congenital
      cardiovascular diseases had a higher prevalence of periodontal disease, evidenced
      by gingivitis, plaque, calculus, and recession. These children should be
      evaluated periodontally and their oral health monitored on a 3-month basis to
      prevent disease development, benefit cardiovascular condition, prevent
      endocarditis, and improve quality and longevity of life.

PMID- 24290562
TI  - Exercise training modalities and strategies to improve exercise performance in
      patients with respiratory disease.
AB  - Pulmonary rehabilitation is an evidence-based, multidisciplinary, comprehensive
      intervention for patients with chronic respiratory diseases who are symptomatic
      and whose daily living activities are often restricted. Pulmonary rehabilitation
      programs are designed to improve the physical and emotional condition of people
      with chronic respiratory disease and to promote long-term adherence to health
      enhancing behavior. Exercise training is at the core of pulmonary rehabilitation
      (PR) programs. The benefits of exercise training include decreased dyspnea,
      improved health-related quality of life, fewer days of hospitalization, and
      decreased health-care utilization. To gain PR benefits, patients should be able
      to complete an exercise training program, preferably with high intensity
      exercise, and it is likely that these benefits will translate into a change from
      a pattern of a sedentary lifestyle to a physically active lifestyle. Chronic
      respiratory patients, namely COPD patients, have a low exercise tolerance due to
      multiple factors, such as dynamic hyperinflation and peripheral muscle
      dysfunction. In this article, the authors describe a variety of modalities and
      strategies to overcome exercise limitations and improve the effects of exercise
      training.

PMID- 24290563
TI  - Implementation of a guideline for physical therapy in the postoperative period of
      upper abdominal surgery reduces the incidence of atelectasis and length of
      hospital stay.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of
      implementing a physical therapy guideline for patients undergoing upper abdominal
      surgery (UAS) in reducing the incidence of atelectasis and length of hospital
      stay in the postoperative period. MATERIALS AND METHODS: A "before and after"
      study design with historical control was used. The "before" period included
      consecutive patients who underwent UAS before guideline implementation
      (intervention). The "after" period included consecutive patients after guideline
      implementation. Patients in the pre-intervention period were submitted to a
      program of physical therapy in which the treatment planning was based on the
      individual experience of each professional. On the other hand, patients who were
      included in the post-intervention period underwent a standardized program of
      physical therapy with a focus on the use of additional strategies (EPAP,
      incentive spirometry and early mobilization). RESULTS: There was a significant
      increase in the use of incentive spirometry and positive expiratory airway
      pressure after guideline implementation. Moreover, it was observed that early
      ambulation occurred in all patients in the post-intervention period. No patient
      who adhered totally to the guideline in the post-intervention period developed
      atelectasis. Individuals in the post-intervention period presented a shorter
      length of hospital stay (9.2+/-4.1 days) compared to patients in the pre
      intervention period (12.1+/-8.3 days) (p<0.05). CONCLUSION: The implementation of
      a physical therapy guideline for patients undergoing UAS resulted in reduced
      incidence of atelectasis and reduction in length of hospital stay in the
      postoperative period.

PMID- 24290564
TI  - The impact of display angles on the legibility of Sans-Serif 5 * 5 capitalized
      letters.
AB  - This paper introduced a laboratory study on quantifying the impact of display
      angles 0.0 degrees -90.0 degrees  on the legibility of Sans-Serif 5 * 5
      Capitalized Letters C, D, E, F, H, K, N, P, R, U, V, and Z, commonly used for
      acuity tests. This study addressed three issues not tackled in the previous
      studies, including (a) extremely large incident angles 82.8 degrees -90 degrees ,
      (b) multiple letters other than a single letter E previously used, and (c) the
      interference of people's normal reading habit on legibility evaluation. A total
      of 20 young college students with Snellen acuity 20/20 or better and normal color
      vision participated in this experiment. They were asked to read viewing materials
      presented at 15 display angles. This study derived two equations and modified an
      existing legibility index to correct the interference of people's normal reading
      habit on legibility evaluation at extreme oblique display angles.

PMID- 24290565
TI  - Correlations between ovarian follicular blood flow and superovulatory responses
      in ewes.
AB  - The primary goal of this study was to employ ultrasonography to examine the
      ovaries of ewes undergoing superovulatory treatment for correlations between
      antral follicular blood flow and ovarian responses/embryo yields. Five Santa Ines
      ewes were subjected to a short- (Days 0-6, Group 1) and five to a long-term
      progesterone-based protocol (Days 0-12, Group 2) to synchronize estrus and
      ovulations after the superovulatory treatment. Porcine FSH (pFSH, 200mg) was
      administered in 8 decreasing doses over 4 days, starting on Days 4 and 10 in
      Groups 1 and 2, respectively. After CIDR removal, all ewes were bred by a ram and
      embryos were recovered surgically 7 days later. Transrectal ovarian
      ultrasonography was performed the day before and on all 4 days of the
      superovulatory treatment. Both an arbitrary-scale [(0) non-detectable; (1) small;
      (2) moderate; (3) intense blood flow] and quantitative analysis of the blood flow
      area were used to assess the follicular blood flow in color Doppler images. There
      were no significant correlations between the arbitrary blood flow scores and
      superovulatory responses in the ewes of the present study. However, there was a
      positive correlation between the quantitative estimates of follicular blood flow
      on the final day of the superovulatory treatment, and the number (DA: r=0.68,
      P<0.05; DA/TA*100%: r=0.85, P<0.05) and percentage (DA: r=0.65, P<0.05;
      DA/TA*100%: r=0.91, P<0.001) of unfertilized eggs (DA: Doppler area, TA: total
      area of the largest ovarian cross section). This experiment presents a
      commercially practical tool for predicting superovulatory outcomes in ewes and
      evidence for the existence of follicular blood flow threshold that may impinge
      negatively on oocyte quality when surpassed during hormonal ovarian
      superstimulation. 

PMID- 24290566
TI  - The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II
      (MTII), against binge-like ethanol drinking are facilitated by deletion of the
      MC3 receptor in mice.
AB  - Recent data have implicated the melanocortin (MC) system in modulating voluntary
      ethanol consumption. Administration of melanotan-II (MTII), a nonselective
      melanocortin receptor (MCR) agonist, reduces voluntary ethanol consumption in
      C57BL/6J mice. Previous studies have demonstrated that central infusion of MTII
      effectively reduced voluntary ethanol drinking in mutant mice lacking normal
      expression of MC3R (MC3R-/- mice) but failed to alter ethanol drinking in mice
      lacking expression of MC4R, demonstrating that central MTII administration
      reduces voluntary ethanol drinking by signaling through the MC4R. However,
      evidence shows that the neurocircuitry recruited during excessive binge-like
      ethanol drinking versus moderate ethanol drinking are not identical. Thus the
      present study sought to investigate the potential role of the MC3R in binge-like
      ethanol intake. To this end, the "drinking in the dark" (DID) procedure, a
      commonly used animal model of binge-like ethanol drinking, was employed. Wild
      type MC3R+/+ and MC3R-/- mice were given intracerebroventricular (i.c.v.)
      infusion of MTII (0.0, 0.25, 0.50, or 1.0 MUg) prior to the onset of a 4-h
      testing period in which mice were given access to 20% (v/v) ethanol. Immediately
      after the 4-h testing period, tail blood samples were collected from each animal
      in order to assess blood ethanol concentrations (BECs). Consistent with previous
      findings, central administration of MTII blunted binge-like ethanol drinking in
      both MC3R+/+ and MC3R-/- mice. Interestingly, all doses of MTII blunted binge
      like ethanol drinking in MC3R-/- mice during the first hour of testing, while
      only the 1.0 MUg dose reduced binge-like drinking in MC3R+/+ mice. Thus, MC3R-/-
      mice were more sensitive to the protective effects of MTII. These data suggest
      that MC3Rs oppose the protective effects of MTII against binge-like ethanol
      drinking, and thus selective MC3R antagonists may have potential therapeutic
      roles in treating excessive ethanol drinking.

PMID- 24290567
TI  - Impact of coronary artery calcium characteristics on accuracy of CT angiography.
AB  - OBJECTIVES: This study sought to evaluate which specific calcium characteristics
      impact diagnostic accuracy of coronary computed tomography angiography (CTA).
      BACKGROUND: Coronary calcifications comprise one of the most significant factors
      interfering with diagnostic accuracy of coronary CTA. Despite this fact, there is
      paucity of data regarding this phenomenon. METHODS: A total of 525 coronary
      lesions (252 calcified and 273 reference [noncalcified] lesions) within 97
      arteries of 60 patients (19 women, age 63 +/- 10 years) underwent assessment with
      both 2 * 64-slice computed tomography and intravascular ultrasound (IVUS).
      Nineteen calcium characteristics were determined. The main outcome was coronary
      CTA inaccuracy defined as the deviation of minimum lumen area within the
      calcification measured with coronary CTA from that measured with IVUS, in both
      absolute (mm(2)) and relative (%) terms. RESULTS: Presence of calcification was
      found to be independently correlated to coronary CTA inaccuracy in both absolute
      and relative terms (p < 0.001 for both). The relative (%) inaccuracy of coronary
      CTA was independently correlated to total calcium length (p = 0.004), total
      calcium volume (p = 0.008), cross section calcium thickness (p = 0.023), cross
      section calcium area (p = 0.023), and cross section lumen area (p = 0.001). The
      absolute inaccuracy of CTA was correlated to calcium length (p = 0.010), calcium
      volume (p = 0.017), and cross section calcium area (p < 0.001). The presence of
      both total calcium arc >=47 degrees  and mean lumen diameter of <=2.8 mm provided
      the best predictive accuracy for detection of excessive lumen underestimation by
      CTA. The best accuracy for prediction of excessive lumen overestimation provided
      combination of 2 of 3 features: maximum calcium density <869 HU, OR whole calcium
      length <2.4 mm, OR total calcium volume <6.4 mm(3). CONCLUSIONS: Our results
      indicate which specific calcium characteristics impact accuracy of coronary CTA
      in lumen assessment within calcified lesions. This may provide practical
      assistance in predicting coronary lumen underestimation or overestimation by
      coronary CTA, therefore mitigating risk of diagnostic errors in clinical
      practice.

PMID- 24290568
TI  - Acute mortality in critically ill patients undergoing echocardiography with or
      without an ultrasound contrast agent.
AB  - OBJECTIVES: The objective of this observational study was to compare 48-h all
      cause mortality (as well as hospital stay mortality) among critically ill
      patients who underwent echocardiography either with or without an ultrasound
      contrast agent (UCA). BACKGROUND: The safety of perflutren-based UCAs has been
      questioned by the U.S. Food and Drug Administration (particularly when
      administered to critically ill patients) following rare reports of deaths or life
      threatening adverse reactions that occurred in close temporal relationship to UCA
      administration. METHODS: This was a retrospective observational outcome study
      conducted in critically ill patients to compare all-cause 48-h and hospital stay
      mortality subsequent to echocardiography procedures performed either with or
      without a UCA. The study utilized discharge data from a database maintained by
      Premier, Inc. (Charlotte, North Carolina). Premier's database is the largest U.S.
      hospital-based, service-level comparative database for quality and outcomes
      research, and provides detailed resource utilization data along with patients'
      primary and secondary diagnoses and procedure billing codes. A propensity score
      matching algorithm between UCA-enhanced echocardiography patients and non
      contrast-enhanced echocardiography patients was utilized to reduce the potential
      for imbalance in covariates of selected patients in the comparison of mortality
      between groups. RESULTS: Patients undergoing echocardiography with a UCA had
      lower mortality at 48 h compared with patients undergoing non-contrast-enhanced
      echocardiography (1.70% vs. 2.50%), with an odds ratio = 0.66 (95% confidence
      interval [CI]: 0.54 to 0.80). Patients undergoing echocardiography with a UCA had
      lower hospital stay mortality compared with patients undergoing noncontrast
      echocardiography (14.85% vs. 15.66%), with an odds ratio = 0.89 (95% CI: 0.84 to
      0.96). CONCLUSIONS: In critically ill, propensity-matched hospitalized patients
      undergoing echocardiography, use of a UCA is associated with a 28% lower
      mortality at 48 h in comparison with patients undergoing non-contrast-enhanced
      echocardiography. These results are reassuring, given previous reports suggesting
      an association between UCAs and increased mortality in critically ill patients.

PMID- 24290569
TI  - Exercise echocardiography in asymptomatic HCM: exercise capacity, and not LV
      outflow tract gradient predicts long-term outcomes.
AB  - OBJECTIVES: This study sought to assess long-term outcomes in asymptomatic or
      minimally symptomatic patients with hypertrophic cardiomyopathy (HCM) who
      underwent exercise echocardiography, without invasive therapies for relief of
      left ventricular outflow tract (LVOT) obstruction. BACKGROUND: Many HCM patients
      present with LVOT obstruction, mitral regurgitation (MR), and diastolic
      dysfunction, often requiring invasive therapies for symptomatic relief. However,
      a significant proportion of truly asymptomatic patients can be closely monitored.
      In HCM patients, exercise echocardiography has been shown to be a useful
      assessment of functional capacity and risk stratification. METHODS: We included
      426 HCM patients (44 +/- 14 years; 78% men) undergoing exercise echocardiography,
      excluding hypertensive heart disease of elderly, ejection fraction <50% and
      invasive therapy (myectomy or alcohol ablation) during follow-up. Clinical,
      echocardiographic (LV thickness, LVOT gradient, and MR) and exercise variables
      (percent of age-sex predicted metabolic equivalents [METs] and heart rate
      recovery [HRR] at 1 min post-exercise) were recorded. A composite endpoint of
      death, appropriate internal defibrillator discharge, and admission for congestive
      heart failure was recorded. RESULTS: Patients were asymptomatic or minimally
      symptomatic on history, but 82% of patients achieved <100% of age-sex predicted
      METs, and 43% had >=II+ post-stress MR. The mean LV septal thickness, post
      exercise LVOT gradient, and HRR were 2.0 +/- 0.5 cm, 62 +/- 47 mm Hg, and 31 +/-
      14 beats/min, respectively. During a mean follow-up of 8.7 +/- 3 years, there
      were 52 events (12%). Patients achieving >100% of age-sex predicted METs had 1%
      event rate versus 12% in those achieving <85%. On stepwise multivariate survival
      analysis, percent of age-sex predicted METs (hazard ratio [HR]: 0.76; 95%
      confidence interval [CI]: 0.64 to 0.90), abnormal HRR (HR: 0.89; 95% CI: 0.82 to
      0.97), and atrial fibrillation (HR: 2.73; 95% CI: 1.30 to 5.74) (overall, p <
      0.001) independently predicted outcomes. CONCLUSIONS: In asymptomatic or
      minimally symptomatic HCM patients, exercise stress testing provides excellent
      risk stratification, with a low event rate in patients achieving >100% of
      predicted METs.

PMID- 24290571
TI  - Magnesium intake is inversely associated with coronary artery calcification: the
      Framingham Heart Study.
AB  - OBJECTIVES: The aim of this study was to examine whether magnesium intake is
      associated with coronary artery calcification (CAC) and abdominal aortic
      calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium
      may prevent calcification within atherosclerotic plaques underlying
      cardiovascular disease. Little is known about the association of magnesium intake
      and atherosclerotic calcification in humans. METHODS: We examined cross-sectional
      associations of self-reported total (dietary and supplemental) magnesium intake
      estimated by food frequency questionnaire with CAC and AAC in participants of the
      Framingham Heart Study who were free of cardiovascular disease and underwent
      Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695;
      age: 53 +/- 11 years), using multivariate-adjusted Tobit regression. CAC and AAC
      were quantified using modified Agatston scores (AS). Models were adjusted for
      age, sex, body mass index, smoking status, systolic blood pressure, fasting
      insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone
      replacement therapy (women only), menopausal status (women only), treatment for
      hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as
      well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber,
      alcohol, and energy. Secondary analyses included logistic regressions of CAC and
      AAC outcomes as cut-points (AS >0 and AS >=90th percentile for age and sex), as
      well as sex-stratified analyses. RESULTS: In fully adjusted models, a 50-mg/day
      increment in self-reported total magnesium intake was associated with 22% lower
      CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations,
      the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34%
      lower (p trend: 0.01), in those with the highest compared to those with the
      lowest magnesium intake. Stronger inverse associations were observed in women
      than in men. CONCLUSIONS: In community-dwelling participants free of
      cardiovascular disease, self-reported magnesium intake was inversely associated
      with arterial calcification, which may play a contributing role in magnesium's
      protective associations in stroke and fatal coronary heart disease.

PMID- 24290572
TI  - A urethane-based multimethacrylate mixture and its use in dental composites with
      combined high-performance properties.
AB  - OBJECTIVES: To synthesize and characterize different molar weight urethane
      multimethacrylates with a single stage (one-pot) procedure. To prepare and
      characterize the properties of related composites. METHODS: Two methacrylate
      precursors were initially synthesized. Then, these precursors and the
      multimethacrylate system formed by their coupling were characterized by FTIR and
      (1)H NMR. The final product was used as a matrix (with TEGDMA and SiO2 silanized
      microparticles) in the preparation of composites and their physical and
      mechanical properties were compared to those of a bis-GMA-based resin. Water
      sorption and solubility measurements of the composites were also performed.
      RESULTS: FTIR and NMR suggested that the proposed synthesis route yields a
      mixture of mainly urethane-di, -tri, and tetramethacrylates. The composites
      presented low polymerization shrinkage (e.g. 1.88+/-0.08% for a resin with 70% of
      SiO2) and high flexural strength (e.g. 124.74+/-9.68 MPa for a resin with 65% of
      SiO2) when compared to the bis-GMA based resin and other composites found to
      date. Water sorption and solubility results show that the composites were deemed
      compliant with ISO 4049 requirements. SIGNIFICANCE: The mixture containing
      different molar weight of urethane multimethacrylates showed to be an excellent
      substitute for bis-GMA, achieving an equilibrium of properties (unlike reports
      elsewhere which show the enhancement of some parameters in detriment to others)
      and composites with low polymerization shrinkage, suitable microhardness and
      degree of conversion, and up to standard water sorption/solubility and flexural
      strength.

PMID- 24290570
TI  - Myocardial extracellular volume expansion and the risk of recurrent atrial
      fibrillation after pulmonary vein isolation.
AB  - OBJECTIVES: This study tested whether myocardial extracellular volume (ECV) is
      increased in patients with hypertension and atrial fibrillation (AF) undergoing
      pulmonary vein isolation and whether there is an association between ECV and post
      procedural recurrence of AF. BACKGROUND: Hypertension is associated with
      myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are
      limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic
      resonance (CMR) study provide a method for quantification of ECV. METHODS:
      Consecutive patients with hypertension and recurrent AF referred for pulmonary
      vein isolation underwent a contrast CMR study with measurement of ECV and were
      followed up prospectively for a median of 18 months. The endpoint of interest was
      late recurrence of AF. RESULTS: Patients had elevated left ventricular (LV)
      volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34
      +/- 0.03; healthy control patients, 0.29 +/- 0.03; p < 0.001). There were
      positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and
      LV mass and a negative association between ECV and diastolic function (early
      mitral annular relaxation [E'], r = -0.55, p < 0.001). In the best overall
      multivariable model, ECV was the strongest predictor of the primary outcome of
      recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p <
      0.0001) and the secondary composite outcome of recurrent AF, heart failure
      admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51;
      p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of
      recurrent AF. CONCLUSIONS: In patients with AF and hypertension, expansion of ECV
      is associated with diastolic function and left atrial remodeling and is a strong
      independent predictor of recurrent AF post-pulmonary vein isolation.

PMID- 24290574
TI  - Clinical results of microfluidic antibody-independent peripheral blood
      circulating tumor cell capture for the diagnosis of lung cancer.
AB  - OBJECTIVES: The ability to capture and characterize peripheral blood circulating
      tumor cells has the potential for the development of a blood test for cancer. The
      aim of this study was to evaluate the diagnostic performance of microfluidic
      technology as a proof-of-concept study. METHODS: Blood from patients undergoing
      surgery for known or suspected lung cancer was obtained and processed using a
      microfluidic biochip. Diagnostic performance was evaluated against the reference
      of cancer identified within surgically obtained formalin-fixed paraffin embedded
      specimens reported by a principal pathologist. Agreement was assessed in a sample
      reported by a second independent pathologist. Sensitivity- and specificity
      weighted analyses were undertaken. RESULTS: From March 2011 to October 2012, 46
      patients at our institution donated blood for research. Cancer was the underlying
      diagnosis in 43 (94%); 34 (79%) of the patients had primary lung cancer. The
      proportion of patients with cancer in which atypical cells suspicious for cancer
      were identified on hematoxylin and eosin staining was 16/43 (37%) by the
      principal pathologist and 10/17 (59%) by the second pathologist. On sensitivity
      weighted analysis, the sensitivity of the biochip was 54% (95% confidence
      interval [CI], 37-72) and the specificity was 33% (95% CI, 2-91). On specificity
      weighted analysis, the sensitivity was 43% (95% CI, 21-71) and the specificity
      was 100% (95% CI, 5-100). CONCLUSIONS: This work highlights the potential of
      microfluidic technology to develop a blood test for the diagnosis of cancer using
      peripheral blood; conventional clinical criteria can be used as a proof-of
      concept of what may be possible with today's technology.

PMID- 24290573
TI  - Laryngopharyngeal dysfunction independent of vocal fold palsy in infants after
      aortic arch interventions.
AB  - OBJECTIVE: Laryngopharyngeal dysfunction contributes significantly to morbidity,
      length of stay, and increased resource utilization after aortic arch
      interventions in infants. Previous studies have focused on postoperative
      evaluation of selected symptomatic patients with vocal fold palsy (VFP). A
      prospective evaluation of laryngopharyngeal function was undertaken to assess and
      determine its importance in perioperative management. PATIENTS AND METHODS: A
      routine preoperative and postoperative assessment was done by flexible fiber
      optic laryngoscopy, oral feeding evaluation (OFE), and modified barium swallow
      (mBS) on 101 infants undergoing 113 procedures on the aortic arch (2003 to 2011).
      The primary outcome was the ability to take full nutrition orally at discharge.
      RESULTS: Preoperative OFE was abnormal in 33.3% of patients. VFP occurred in
      39.3%, 30 of 57 patients had an abnormal OFE. Factors predictive of abnormal
      postoperative feeding evaluation included genetic syndromes (odds ratio [OR],
      5.1; confidence interval [CI], 1.1-23.2) and preoperative mechanical ventilation
      (OR, 24.1; 95% CI, 2.5-226.6). An abnormal postoperative OFE was highly
      predictive (OR, 7.0; 95% CI, 1.8-27.1) of an abnormal postoperative mBS. There
      was a trend toward decreased long-term survival among patients who were intubated
      or had an abnormal preoperative feeding evaluation (P = .07). CONCLUSIONS:
      Postoperative laryngopharyngeal dysfunction is common among infants undergoing
      aortic arch interventions, and is largely independent of vocal fold function.
      Preoperative evaluation demonstrates significant intrinsic abnormalities in
      sensory and motor function. Routine, comprehensive, multimodality preoperative
      and postoperative evaluation is required to identify at-risk children and reduce
      morbidity and resource utilization.

PMID- 24290577
TI  - Is radiotherapy necessary for pleomorphic adenoma?

PMID- 24290575
TI  - Patterns of survival and recurrence after surgical treatment of early stage non
      small cell lung carcinoma in the ACOSOG Z0030 (ALLIANCE) trial.
AB  - OBJECTIVE: Surgical resection has been the mainstay of curative treatment of
      early stage lung cancer in selected patients. We evaluated survival and patterns
      of recurrence after surgical resection for early stage lung cancer from the
      American College of Surgeons Oncology Group Z0030/Alliance trial. METHODS: One
      thousand eighteen patients enrolled in the Z0030 trial were analyzed according to
      clinical T stage. Differences between groups were compared using the 2-sample
      rank test or chi(2) test. Log rank test and Cox proportional hazards regression
      were used to compare survival and recurrence. To compare patients who underwent
      open versus video-assisted thoracoscopic surgery (VATS) resections, propensity
      score matched analysis was performed. Seven hundred fifty-two patients (66
      undergoing VATS and 686 undergoing open surgery) were classified into 5 equal
      sized propensity-score groups. Proportional hazards regression was used to
      compare these outcomes. RESULTS: There were 578 patients with cT1 tumors and 440
      patients with cT2 tumors. Median follow-up was 6.7 years. Median overall survival
      was 9.1 years (stage T1) and 6.5 years (stage T2). Overall survival at 5 years
      was 72% (stage T1) and 55% (stage T2). Local recurrence-free survival at 5 years
      was 95% (stage T1) and 91% (stage T2) (P = .015). Among patients with stage T1
      cancer, 4.2% (23 out of 542) had local recurrences, whereas 7.3% (30 out of 409)
      of those with stage T2 tumors had local failure. There was no difference in the
      development of new primary tumors between stage T1 and stage T2 groups. In the
      propensity-score matched analysis of VATS versus open lobectomy patients, there
      was no difference in overall survival, disease-free survival, and freedom from
      development of a new primary tumor. CONCLUSIONS: Results of patients with
      resected early stage non-small cell carcinoma from a large-scale, multicenter
      trial serve as benchmarks against which to compare nonsurgical therapies for
      early stage lung cancer. Propensity-score matched analysis shows no difference in
      survival between patients undergoing VATS and open lobectomy.

PMID- 24290578
TI  - The predictive role of dual source CT for esophageal foreign bodies.
AB  - INTRODUCTION: Esophageal foreign bodies can be a danger to a patient's life.
      Flexible or rigid endoscopy is a commonly used type of invasive investigation for
      these, and radiological examinations are also useful. STUDY DESIGN: Series of
      reports. METHODS AND RESULTS: Multi-slice spiral CT (MSCT) can confirm and locate
      most foreign bodies. Dual source CT (DSCT) is a more advanced technique with
      double speed, 20% of the radiation dosage and higher resolution, so it is more
      suitable for possible esophageal foreign bodies, especially in children, with no
      need for sedation. We provide a preliminary experiment of a DSCT scan of two
      fish, and we present a series of 11 cases with DSCT scans of which 5 were
      positive. CONCLUSIONS: Timely diagnosis and accurate localization are paramount
      for endoscopy. DSCT is very useful for diagnosis and evaluation of esophageal
      foreign bodies.

PMID- 24290579
TI  - A submucosal esophageal fish bone foreign body surgically removed using
      intraoperative ultrasonography.
AB  - A 68 year-old female was referred to our department with a history of swallowing
      a fish bone, she reported continuous pain when swallowing. The bone was not
      evident on endoscopic examination; however, on CT scans a foreign body was
      identified in the upper esophagus. The bone was buried in the mucosa of the upper
      esophagus and an emergent rigid esophagoscopy was performed under general
      anesthesia in order to remove it. The fish bone was successfully removed with the
      use of intraoperative cervical ultrasonography.

PMID- 24290580
TI  - Sex, health, and society: ensuring an integrated response.

PMID- 24290581
TI  - Helping smokers quit in secondary-care services.

PMID- 24290582
TI  - The two-child policy in China: what to expect?

PMID- 24290584
TI  - WHO's new guidelines for antiretroviral treatment.

PMID- 24290585
TI  - WHO's new guidelines for antiretroviral treatment.

PMID- 24290586
TI  - WHO's new guidelines for antiretroviral treatment - Authors' reply.

PMID- 24290587
TI  - Singapore's health-care financing.

PMID- 24290588
TI  - Mathematics in medicine: the 300-year legacy of iatromathematics.

PMID- 24290589
TI  - Rash and arthralgia caused by hepatitis E.

PMID- 24290590
TI  - Pleuritic chest pain.

PMID- 24290591
TI  - Today's and yesterday's of pathophysiology: biochemistry of metabolic syndrome
      and animal models.
AB  - During the past 20 y, there has been much interest in sugars and especially
      fructose in relation to human health. Over the past decade, considerable
      scientific debate and controversy have arisen about the potential health effects
      of sucrose, high-fructose corn syrup (HFCS), and fructose itself. HFCS
      increasingly has been used as a sweetener in thousands of food products and soft
      drinks, leading to the development of obesity, diabetes, dyslipidemia, and
      metabolic syndrome (MetS) in both rodents and humans, which is associated with an
      increase in body weight. There is a need for detailed research on the mechanism
      underlying MetS that could lead to a remedy. This review will first
      systematically present a definition of MetS, its history, prevalence, and
      comparative diagnostic criteria. We will then consider fructose and its effects
      on human health, the diet-induced obesity model (various fat contents), the
      hypercholesterolemic model, the diabetes model, the hypertensive model, the MetS
      or insulin resistance model, and biomarkers related to MetS, in light of
      contemporary data using multiple databases (PubMed, MEDLINE, and OVID).

PMID- 24290592
TI  - Does diet-induced weight change effect anxiety in overweight and obese adults?
AB  - Anxiety is the most prevalent type of mental disorder and a significant health
      concern. Cross-sectional studies have detected a positive association between
      obesity and anxiety. What is less clear is whether weight loss can reduce
      anxiety. We sought to answer three questions: 1. Can weight loss improve symptoms
      of anxiety in the overweight and obese population? 2. Does the macronutrient
      content of energy-restricted diets that induce weight loss affect anxiety? 3. Is
      the change in anxiety related to the amount of weight lost? We investigated the
      findings from seven interventional studies, which induced weight loss by dietary
      intervention, in overweight and obese individuals, using established anxiety
      assessment tools. Mean weight loss ranged from 0.7 to 18.6 kg (SD 4.5) and in
      three of the studies, anxiety fell by 9.2% to 11.4% and did not change in four
      studies. When macronutrient content was considered, only one of four
      interventional studies and one pilot study reported a beneficial effect of a
      moderate-fat diet on anxiety. There appears to be no strong evidence to indicate
      that diet-induced weight loss has a beneficial effect on anxiety, however, none
      of the diet-induced weight loss studies assessed had a detrimental effect on
      anxiety. 

PMID- 24290593
TI  - Pathologic bone alterations in celiac disease: etiology, epidemiology, and
      treatment.
AB  - Low bone mineral density (BMD), osteopenia, and osteoporosis are frequent
      complications of celiac disease (CD). The etiology of pathologic bone alterations
      in CD is multifactorial; however, two main mechanisms are involved: intestinal
      malabsorption and chronic inflammation. A strict gluten-free diet (GFD) is
      thought to be the only effective treatment for CD; but treating bone
      complications related to CD remains complex. The objective of this review is to
      elucidate the bones problems related to CD and to increase awareness of
      osteoporosis development, considered as a sign of atypical CD presentation.
      Currently, a question of whether GFD alone is an effective treatment to correct
      the bone alterations in patients with CD is under debate. This review presents
      factors contributing to pathologic bone derangement, recent research on the
      epidemiology of low BMD, osteoporosis, and fractures, and the treatment of bone
      problems in patients with CD. The roles of calcium and transport mechanisms are
      additionally presented. 

PMID- 24290594
TI  - Yeast hydrolysate can reduce body weight and abdominal fat accumulation in obese
      adults.
AB  - OBJECTIVE: The aim of this study was to examine the effect of yeast hydrolysate
      on the abdominal fat in obese humans. METHODS: We observed the effects of yeast
      hydrolysate that had a molecular weight below 10 kDa on the anti-abdominal fat
      accumulation in obese men and women ages 20 to 50 y for 10 wk. The abdominal fat
      mass was assessed by computed tomographic scans. RESULTS: By the sixth week, the
      reductions in energy intake in the yeast group (yeast hydrolysate 1 g/d) were
      significantly greater than those in the control group (placebo 1 g/d) (P < 0.05).
      The body weight and body mass index (BMI) were significantly reduced by week 10
      compared with baseline in the yeast group, and these differences were
      significantly greater than those in the control group: body weight 0.83 kg versus
      -2.60 k g (P < 0.001), BMI 0.29 kg/m(2) versus -0.90 kg/m(2) (P < 0.001). Despite
      the increased loss of body weight in the yeast group, lean body mass did not
      significantly differ between the two groups. Body fat mass in the control group
      did not significantly change between baseline and week 10. However, the yeast
      group lost a significant amount of body fat mass after 10 wk of treatment (P <
      0.01). The differences in abdominal fat thickness and abdominal circumference
      between the two groups were significant after 10 wk of treatment (P < 0.001). The
      total abdominal fat area in the yeast group was significantly lower than in the
      control group after 10 wk of treatment (-7.06 cm(2) versus -17.34 cm(2); P <
      0.01). CONCLUSIONS: Yeast hydrolysate can reduce body weight and the accumulation
      of abdominal fat without an adverse effect on lean body mass in obese adults,
      regardless of sex, via the reduction of energy intake.

PMID- 24290595
TI  - National report on the association of serum vitamin D with cardiometabolic risk
      factors in the pediatric population of the Middle East and North Africa (MENA):
      the CASPIAN-III Study.
AB  - OBJECTIVES: As the first, to our knowledge, nationwide study in the Middle East
      and North Africa (MENA), this study aimed to investigate the association of serum
      25 hydroxy vitamin D [25(OH)D] levels with cardiometabolic risk factors in a
      nationally representative sample of the pediatric population in Iran. The second
      objective was to provide the prevalence of hypovitaminosis D and the percentiles
      of serum 25(OH)D in the study population. METHODS: This national population-based
      study was conducted among 1100 Iranian students living in 27 provinces in Iran.
      The association of 25(OH)D with each cardiometabolic risk factor was determined
      after adjustment for age, gender, body mass index, and waist circumference.
      RESULTS: Participants consisted of 1095 students (52% boys) with a mean age of
      14.74 +/- 2.61 y. The median 25(OH)D level corresponded to a vitamin D
      insufficiency level: 12.70 ng/mL in boys and 13.20 ng/mL in girls. Overall, 40%
      of participants were vitamin D deficient, and 39% had vitamin D insufficiency.
      There were no significant differences in these findings between boys and girls.
      Adjusted regression analysis revealed a significant weak inverse association of
      25(OH)D with systolic blood pressure, diastolic blood pressure, total
      cholesterol, and low-density lipoprotein cholesterol. This association was
      significantly positive with high-density lipoprotein cholesterol, but not with
      fasting plasma glucose and metabolic syndrome. CONCLUSION: We found a
      considerably high prevalence of hypovitaminosis D in the pediatric population of
      a sunny region. Our findings also revealed an association of hypovitaminosis D
      with many cardiometabolic risk factors from childhood; these associations were
      independent of obesity indexes. It is of special concern that the highly
      prevalent disorders of low 25(OH)D and low high-density lipoprotein cholesterol
      in children and adolescents of the MENA region had significant association. The
      clinical importance of our findings needs to be confirmed in longitudinal
      studies.

PMID- 24290596
TI  - Birth weight predicts the risk of gestational diabetes mellitus and pregravid
      obesity.
AB  - OBJECTIVES: It has been suggested that birth weight may determine metabolic
      abnormalities later in life. The aim of the current study was to assess the
      association between birth weight and future risk of gestational diabetes mellitus
      (GDM) and pregravid obesity in a homogenous sample of Caucasian Polish women.
      METHODS: In this retrospective study, we collected the medical reports of 787
      women with GDM and 801 healthy pregnant women. We analyzed the following data:
      birth weight, age, pregravid weight, prior GDM, prior macrosomia, parity, and
      family history of diabetes. RESULTS: Birth weight was inversely associated with
      the risk of GDM; for each decrease in birth weight of 500 g, the risk increased
      by 11% (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02-1.21). Birth
      weight was a strong predictor of GDM independent of other risk factors (OR, 1.19;
      95% CI, 1.09-1.31), and it was positively correlated with pregravid weight (R =
      0.21; P < 0.00001). An increase in birth weight of 500 g substantially increased
      the risk of overweight and obesity (OR, 1.17; 95% CI, 1.01-1.34 and OR, 1.35; 95%
      CI 1.11-1.64, respectively). Each of the traditional risk factors for GDM were
      also strong predictors of pregravid obesity: age (P < 0.0001), prior GDM (P <
      0.01), prior macrosomia (P < 0.0001), multiparity (P < 0.0001), and maternal (but
      not paternal) history of diabetes (P < 0.0001). CONCLUSIONS: Among Caucasian
      Polish women, the risk of GDM is associated with low birth weight, and pregravid
      obesity is associated with high birth weight. Traditional risk factors for GDM,
      including maternal (but not paternal) history of diabetes, are also risk factors
      for pregravid obesity.

PMID- 24290597
TI  - One-month of calcium supplementation does not affect iron bioavailability: a
      randomized controlled trial.
AB  - OBJECTIVES: Calcium (Ca) and iron (Fe) are essential minerals for normal growth
      and development. Although previous studies have shown that Ca inhibits acute Fe
      absorption, there is no evidence of the possible long- or medium-term effects of
      Ca supplementation on Fe bioavailability. The aim of this study was to determine
      the effect of 34 d of Ca supplementation on heme Fe and non-heme Fe
      bioavailability in non-pregnant women of ages 33 to 47 y. METHODS: This was a
      prospective, randomized, double-blind, placebo-controlled trial. Twenty-six
      healthy women (40 +/- 5 y) were randomly assigned to receive either 600 mg of
      elemental Ca/d as CaCO3 (Ca group, n = 13) or a placebo (P group, n = 13) for 34
      d. Heme Fe and non-heme Fe bioavailability were determined before and after
      treatment using (55)Fe and (59)Fe radioisotopes. A two-factor, repeated-measures
      analysis of variance was used to assess differences by treatment and timing.
      RESULTS: The geometric mean (range +/- 1 SD) of heme Fe bioavailability before
      and after treatment was 16.5% (8.3-32.8) and 26% (15.5-43.6) for the Ca group and
      21.8% (13.0-36.6) and 25.1% (16.5-38.3) for the P group. Non-heme Fe
      bioavailability before and after treatment was 39.5% (19.9-78.7) and 34.1% (19.1
      60.6) for the Ca group, and 44.6% (24.9-79.7) and 39.3% (24.3-63.4) for the P
      group. There were no differences in either heme Fe or non-heme Fe bioavailability
      either at baseline or after treatment. CONCLUSION: The administration of calcium
      supplements for 34 d does not affect iron bioavailability. This trial is
      registered with Controlled-trials.gov, number ISRCTN 89888123.

PMID- 24290598
TI  - Medical weight loss versus bariatric surgery: does method affect body composition
      and weight maintenance after 15% reduction in body weight?
AB  - OBJECTIVE: The aim of this study was to investigate body composition changes in
      fat mass (FM) to lean body mass (LBM) ratios following 15% body weight loss (WL)
      in both integrated medical treatment and bariatric surgery groups. METHODS: Obese
      patients (body mass index [BMI] 46.6 +/- 6.5 kg/m(2)) who underwent laparoscopic
      gastric bypass surgery (BS), were matched with 24 patients undergoing integrated
      medical and behavioral treatment (MT). The BS and MT groups were evaluated for
      body weight, BMI, body composition, and waist circumference (WC) at baseline and
      after 15% WL. RESULTS: Following 15% body WL, there were significant decreases in
      %FM and increased %LBM (P < 0.0001). Additionally, both groups saw 76% of WL from
      FM, and 24% from LBM indicating a 3:1 ratio of FM to LBM loss during the first
      15% reduction in body weight. Finally, no significant differences (P = 0.103)
      between groups for maintenance of WL at 1 y were found. For both groups, baseline
      FM was found to be negatively correlated with percentage of weight regained (%WR)
      at 1 y post-WL (r = -0.457; P = 0.007). Baseline WC and rate of WL to 15% were
      significant predictors of %WR only in the BS group (r = 0.713; P = 0.020).
      CONCLUSION: If followed closely by professionals during the first 15% body WL,
      patients losing 15% weight by either medical or surgical treatments can attain
      similar FM:LBM loss ratios and can maintain WL for 1 y.

PMID- 24290599
TI  - Which dietary diversity indicator is best to assess micronutrient adequacy in
      children 1 to 9 y?
AB  - OBJECTIVES: The aim of this study was to determine the best dietary diversity
      indicator to measure dietary diversity and micronutrient adequacy in children.
      METHODS: A national representative cross-sectional survey of children ages 1 to 9
      y (N = 2,200) was undertaken in all ethnic groups in South Africa. A 24-h recall
      was done with the mother or caregiver of each child. A dietary diversity score
      (DDS), the number of food groups consumed at least once in a period of 24 h, was
      calculated for each child in accordance with 6-, 9-, 13-, and 21-food group (G)
      indicators and compared with a mean adequacy ratio (MAR). The nutrient adequacy
      ratio (NAR) was calculated for 11 micronutrients by comparing the distributions
      of estimated intakes with the Estimated Average Requirements for that
      micronutrient. The MAR was the average of all NARs. Correlations were done
      between MAR and DDS and sensitivity and specificity calculated for each group
      indicator. RESULTS: Pearson's correlations between food group indicators and MAR
      indicate that r values were all highly significant (P < 0.0001). There were no
      consistent or large differences found between the different group indicators
      although G13 and G21 appeared to be marginally better. Sensitivity and
      specificity values in the current study lay between DDS of 3 and 5, suggesting
      one of these as the best indication of (low) micronutrient adequacy. CONCLUSIONS:
      Overall results seem to indicate that any of the four G indicators can be used in
      dietary assessment studies on children, with G13 and G21 being marginally better.
      A cut-off DDS of 4 and 5, respectively, appear best.

PMID- 24290600
TI  - Moderate replacement of carbohydrates by dietary fats affects features of
      metabolic syndrome: a randomized crossover clinical trial.
AB  - OBJECTIVE: Earlier studies on the management of metabolic syndrome (MetS) have
      mostly focused on very low carbohydrate diets, whereas long-term adherence to
      such diets is difficult for apparently healthy people. The aim of this study was
      to examine the effects of moderate replacement of carbohydrates by dietary fats
      on insulin resistance and features of MetS among women. METHODS: This randomized
      crossover clinical trial was performed with 30 overweight or obese (body mass
      index [BMI] > 25 kg/m(2)) women with MetS. After a 2-wk run-in period,
      participants were randomly assigned to consume either a calorie-restricted high
      carbohydrate (HC) diet (60%-65% of energy from carbohydrates and 20%-25% from
      fats) or a calorie-restricted moderately restricted carbohydrate (MRC) diet (43%
      47% of total calories as carbohydrate and 36%-40% as dietary fats) for 6 wk.
      Protein contents of both diets were 15% to 17% of total energy. A 2-wk washout
      period was applied following which participants were crossed over to the
      alternate treatment arm for an additional 6 wk. Anthropometric, blood pressure,
      and biochemical measurements were performed before and after each phase of
      intervention. RESULTS: Mean age and BMI of study participants was 42.4 y and 33
      kg/m(2), respectively. A trend toward greater reduction in waist (-3.9 versus 
      2.6 cm; P = 0.07) and hip circumferences (-2.7 versus -1.5 cm; P = 0.07) as well
      as serum triglyceride (TG) levels (-31.3 versus 0.13 mg/dL; P = 0.07) was
      observed after consumption of an MRC diet compared with an HC diet. The TG to
      high-density lipoprotein cholesterol (HDL-C) ratio had a tendency to improve with
      the MRC diet rather than the HC diet (-0.9 versus -0.1; P = 0.06). Consumption of
      the MRC diet resulted in a greater reduction of systolic blood pressure (-8.93
      versus -2.97 mm Hg; P = 0.06) and diastolic blood pressure (-12.7 versus -1.77 mm
      Hg; P = 0.001) compared with the HC diet. The prevalence of MetS was
      significantly decreased following the consumption of the MRC diet (P = 0.03). The
      two diets were not significantly different in terms of their effect on fasting
      plasma glucose, serum HDL-C, low-density lipoprotein cholesterol, and total
      cholesterol, insulin levels, and Homeostasis Model Assessment-Insulin Resistance.
      CONCLUSION: Moderate replacement of carbohydrates by dietary fats was not
      associated with statistically different changes in fasting plasma glucose,
      insulin, or atherogenic dyslipidemia among individuals with the metabolic
      syndrome; however, it resulted in decreased diastolic blood pressure and lower
      prevalence of the metabolic syndrome.

PMID- 24290601
TI  - Self-reported faster eating associated with higher ALT activity in middle-aged,
      apparently healthy Japanese women.
AB  - OBJECTIVE: Faster eating and elevated circulating activity of alanine
      aminotransferase (ALT), a marker for liver injury, are risk factors for the
      development of obesity and type 2 diabetes mellitus, and their complications. The
      aim of this study was to examine the association between self-reported eating
      rate and circulating ALT activity in apparently healthy middle-aged Japanese
      women. METHODS: We conducted a cross-sectional study of 900 apparently healthy
      women ages 40 to 64 y (mean +/- SD, 53.1 +/- 7.1 y) who participated in health
      check-ups in Japan. We analyzed their clinical serum parameters and lifestyle
      factors, including self-reported eating rate. Associations between liver injury
      markers (ALT, gamma-glutamyl transpeptidase [GTP], and aspartate aminotransferase
      [AST]), other clinical parameters and lifestyle factors were analyzed using
      Tukey's multiple range test following analysis of variance and analysis of
      covariance for three groups, divided by self-reported eating rates. The
      associations between self-reported faster eating and ALT activity and lifestyle
      factors were analyzed by multivariate logistic regression analyses. RESULTS: ALT
      activity, but not gamma-GTP or AST activities, was higher in participants who
      reported relatively fast/very fast eating than in those who reported medium
      eating after adjusting for age, alcohol intake, energy intake, smoking, and
      physical activity. The odds ratio of eating rate for ALT activity in T3 (18-128
      U/L) compared with T1 (3-12 U/L) was 1.67 (P < 0.01), but the association
      disappeared after adjustment for body mass index (BMI). CONCLUSIONS: ALT activity
      is positively associated with faster eating, but is dependent on BMI in middle
      aged, apparently healthy Japanese women.

PMID- 24290602
TI  - Subsarcolemmal and intermyofibrillar mitochondrial responses to short-term high
      fat feeding in rat skeletal muscle.
AB  - OBJECTIVES: We assessed the alterations in mitochondrial function in skeletal
      muscle that were elicited by short-term high-fat feeding in sedentary rats.
      METHODS: Two groups of rats were pair-fed for 1 wk and received a low-fat or high
      fat diet. Body composition, energy balance, and glucose homeostasis were
      measured. Mitochondrial mass, oxidative capacity, and energetic efficiency as
      well as parameters of oxidative stress and antioxidant defense were evaluated in
      subsarcolemmal and intermyofibrillar mitochondria from the skeletal muscle.
      RESULTS: Body energy, lipid content, and metabolic efficiency were significantly
      higher and energy expenditure was significantly decreased among rats that were
      fed a high-fat diet, as compared with controls. Skeletal muscle mitochondrial
      energetic efficiency, oxidative capacity for lipid substrates, and antioxidant
      defense were significantly increased in rats that were fed a high-fat diet as
      compared with controls. CONCLUSIONS: Acute isocaloric high-fat feeding is able to
      induce increased phosphorylation efficiency in skeletal muscle subsarcolemmal and
      intermyofibrillar mitochondria. This modification implies a reduced oxidation of
      energy substrates that may contribute to the early onset of obesity.

PMID- 24290603
TI  - Malnutrition suppresses cell cycle progression of hematopoietic progenitor cells
      in mice via cyclin D1 down-regulation.
AB  - OBJECTIVE: Protein malnutrition (PM) often is associated with changes in bone
      marrow (BM) microenvironment leading to an impaired hematopoiesis; however, the
      mechanism involved is poorly understood. The aim of this study was to compare the
      cell cycle progression of hematopoietic stem cells (HSC) and hematopoietic
      progenitor cells (HPC) and evaluate the cell cycle signaling in malnourished mice
      to assess the mechanism of cell cycle arrest. METHODS: C57Bl/6J mice were
      randomly assigned in control and malnourished groups receiving normoproteic and
      hypoproteic diets (12% and 2% protein, respectively) over a 5-wk period.
      Nutritional and hematologic parameters were assessed and BM immunophenotypic
      analysis was performed. Cell cycle of HPC (Lin(-)) and HSC (Lin(-)Sca-1(+)c
      Kit(+)) were evaluated after 6 h of in vivo 5-bromo-2'-deoxyuridine (BrDU)
      incorporation. Cell cycle regulatory protein expression of HPC was assessed by
      Western blot. RESULTS: Malnourished mice showed lower levels of serum protein,
      albumin, glucose, insulin-like growth factor-1, insulin, and higher levels of
      serum corticosterone. PM also caused a reduction of BM myeloid compartment
      resulting in anemia and leukopenia. After 6 h of BrDU incorporation, malnourished
      mice showed G0-G1 arrest of HPC without changes of HSC proliferation kinetics.
      HPC of malnourished mice showed reduced expression of proteins that induce cell
      cycle (cyclin D1, cyclin E, pRb, PCNA, Cdc25a, Cdk2, and Cdk4) and increased
      expression of inhibitory proteins (p21 and p27) with no significant difference in
      p53 expression. CONCLUSION: PM suppressed cell cycle progression mainly of HPC.
      This occurred via cyclin D1 down-regulation and p21/p27 overexpression attesting
      that BM microenvironment commitment observed in PM is affecting cell interactions
      compromising cell proliferation.

PMID- 24290604
TI  - Genistein antagonizes inflammatory damage induced by beta-amyloid peptide in
      microglia through TLR4 and NF-kappaB.
AB  - OBJECTIVES: Microglia activation and neuroinflammation have been associated with
      the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD).
      Toll-like receptor 4 (TLR4) and nuclear factor (NF)-kappaB-mediated signal
      pathways exert key modulating roles in the inflammatory processes. The aim of the
      present study was to investigate whether genistein (Gen) has a neuroprotective
      effect against inflammatory damage induced by beta-amyloid peptide25-35 (Abeta25
      35) through the TLR4 and NF-kappaB-mediated signal pathways. METHODS: BV-2
      microglia cells were preincubated with Gen for 2 h and then treated with 25 MUM
      Abeta25-35 for another 24 h. The expression of inflammatory mediators, TLR4 and
      NF-kappaB and the activity of NF-kappaB were measured. RESULTS: The results
      showed that Gen could attenuate the cytotoxicity and inflammatory damage induced
      by Abeta25-35. Gen also significantly reversed Abeta25-35-induced up-regulation
      of TLR4 and NF-kappaB expression and the DNA binding and transcriptional
      activities of NF-kappaB. CONCLUSION: These results indicated that Gen could
      alleviate the inflammation caused by Abeta25-35 treatment, which might be
      associated with the regulation of the TLR4/NF-kappaB signal pathway.

PMID- 24290605
TI  - Copper-induced alterations in rat brain depends on route of overload and basal
      copper levels.
AB  - OBJECTIVES: Copper (Cu) is widely used in industry for the manufacture of a vast
      range of goods including Cu-intrauterine devices (IUDs), electronic products,
      agrochemicals, and many others. It is also one of the trace elements essential to
      human health in the right measure and is used as a parenteral supplement in
      patients unable to ingest food. Elevated Cu levels have been found in the plasma
      of women using Cu-IUDs and in farmers working with Cu-based pesticides. However,
      possible alterations due to Cu overload in the brain have been poorly studied.
      Therefore, the aim of this study was to investigate the effects of Cu
      administration on rat brain in Cu-sufficient and Cu-deficient animals fed on semi
      synthetic diets with different doses of Cu (7 or 35 ppm). METHODS: We aimed to
      investigate the effects of Cu administration using two routes of administration:
      oral and intraperitoneal (IP). Male Wistar rats were feeding (one month) a
      complete (7 ppm) or a deficient (traces) Cu diets subdivided into three
      categories oral-, intraperitoneal- (or both) supplemented with copper carbonate
      (7 to 35 ppm). Cu content in plasma, brain zones (cortex and hippocampus),
      antioxidant enzyme activities, and protease systems involved in programmed cell
      death were determined. RESULTS: The results show that Cu levels and the
      concentration of Cu in plasma and brain were dose-dependent and administration
      route-dependent and demonstrated a prooxidative effect in plasma and brain
      homogenates. Oxidative stress biomarkers and antioxidative enzyme activity both
      increased under Cu overload, these effects being more noticeable when Cu was
      administered IP. Concomitantly, brain lipids from cortex and hippocampus were
      strongly modified, reflecting Cu-induced prooxidative damage. A significant
      increase in the activities of calpain (milli- and micro-) and caspase-3 activity
      also was observed as a function of dose and administration route. CONCLUSION: The
      findings of this study could be important in evaluating the role of Cu in brain
      metabolism and neuronal survival.

PMID- 24290606
TI  - Effect of soy product kinako and fish oil on serum lipids and glucose metabolism
      in women with metabolic syndrome.
AB  - OBJECTIVES: At the doses typically used to treat hypertriacylglycerolemia, fish
      oil may increase low-density lipoprotein (LDL) cholesterol and blood glucose
      levels. The aim of the present study was to verify whether soy could attenuate
      the effects of fish oil on blood lipids and carbohydrate metabolism in patients
      with metabolic syndrome. METHODS: Sixty-five women (47.9 +/- 9.98 y) were studied
      with the use of a parallel, randomized design. The control group maintained the
      usual diet; the second group received 29.14 g/d of soy (kinako); the third group
      received 3 g/d of fish oil n-3 fatty acids; and the fourth group received fish
      oil (3 g/d) and kinako (29.14 g/d). Assessments were performed at baseline and
      after 45 and 90 d. RESULTS: In relation to baseline values, fish oil increased (P
      < 0.05) total and LDL cholesterol, glucose, insulin, and homeostasis model
      assessment of insulin resistance levels after 90 d. Comparisons among groups
      demonstrated a decrease (P < 0.05) in total cholesterol in the fish oil and
      kinako group after 90 d as compared with the fish oil group. LDL cholesterol
      decreased (P < 0.01) in the kinako group as compared with the fish oil group.
      Blood glucose and homeostasis model assessment of insulin resistance levels
      decreased after 90 d (P < 0.01 and P < 0.05, respectively) and insulin levels
      decreased (P < 0.05) after 45 d when the kinako group was compared with the fish
      oil group. CONCLUSIONS: The present study showed that kinako moderates the
      adverse effects of high doses of fish oil on LDL cholesterol, total cholesterol,
      and glucose metabolism levels.

PMID- 24290607
TI  - Diarrhea is more dangerous than AIDS in the 21st century.

PMID- 24290608
TI  - Author's response re.: "Diarrhea is more dangerous than AIDS in the 21st
      century".

PMID- 24290609
TI  - Importance of sagittal kick symmetry for underwater dolphin kick performance.
AB  - The purpose of this study was to determine how sagittal kick symmetry in the
      underwater dolphin kick (UDK) between the downkick and upkick phases is related
      to UDK performance. Fifteen adult male competitive swimmers ranging from
      provincial to international level were filmed performing three trials each of
      maximum effort UDK over 15m using an underwater video camera. Video frames were
      manually digitized and each subjects' single fastest trial was evaluated for
      between-subject comparisons. Kinematic variables were calculated for each
      individual and Pearson product-moment correlations between the average horizontal
      centre of mass velocity (Vx) and all kinematic variables were calculated.
      Horizontal velocity during the downkick, horizontal velocity during the upkick,
      relative time spent in each phase, maximum chest flexion angle, maximum knee and
      ankle extension angles, the ratio of flexion/extension for chest, knee and ankle
      angles, and maximum vertical toe velocity during the upkick phase correlated
      significantly with Vx (p<0.05). The ratio of downkick vertical toe
      velocity/upkick vertical toe velocity was significantly negatively correlated
      with Vx (p<0.05). These results indicate the importance of kick symmetry for UDK
      performance, and indicate that performing the upkick phase well appears to be
      most important for UDK performance. 

PMID- 24290610
TI  - Effects of experimentally increased trunk stiffness on thorax and pelvis
      rotations during walking.
AB  - Patients with non-specific low back pain, or a similar disorder, may stiffen
      their trunk, which probably alters their walking coordination. To study the
      direct effects of increasing trunk stiffness, we experimentally increased trunk
      stiffness during walking, and compared the results with what is known from the
      literature about gait coordination with, e.g., low back pain. Healthy subjects
      walked on a treadmill at 3 speeds (0.5, 1.0 and 1.5m/s), in three conditions
      (normal, while contracting their abdominal muscles, or wearing an orthopedic
      brace that limits trunk motions). Kinematics of the legs, thorax and pelvis were
      recorded, and relative Fourier phases and amplitudes of segment motions were
      calculated. Increasing trunk stiffness led to a lower thorax-pelvis relative
      phase, with both a decrease in thorax-leg relative phase, and an increase in
      pelvis-leg relative phase, as well as reduced rotational amplitude of thorax
      relative to pelvis. While lower thorax-pelvis relative phase was also found in
      patients with low back pain, higher pelvis-leg relative phase has never been
      reported in patients with low back pain or related disorders. These results
      suggest that increasing trunk stiffness in healthy subjects causes short-term
      gait coordination changes which are different from those seen in patients with
      back pain. 

PMID- 24290611
TI  - The role of embodied simulation in mental transformation of whole-body images:
      evidence from Parkinson's disease.
AB  - It has been repeatedly demonstrated that mentally performing an action and
      mentally transforming body-parts entail simulation of one's own body movements,
      consistent with predictions of embodied cognition theories. However, the
      involvement of embodied simulation in mental transformation of whole-body images
      is still disputed. Here, we assessed own body transformation in Parkinson's
      disease (PD) patients with symptoms most affecting the left or the right body
      side. PD patients were required to perform left-right judgments on front-facing
      or back-facing human figures, and a letter rotation task. Results demonstrated
      that PD patients were selectively impaired in judging the side of back-facing
      human figures corresponding to their own most affected side, but performed as
      well as healthy subjects on mental transformation of front-facing bodies and on
      letter rotation. These findings demonstrate a parallel impairment between motor
      and mental simulation mechanisms in PD patients, thus highlighting the specific
      contribution of embodied cognition to mental transformation of whole-body images.

PMID- 24290612
TI  - Horse-rider interaction in dressage riding.
AB  - In dressage riding the pelvis of the rider interacts with the horse physically.
      However, there is little information about the influence of riding skill on the
      interaction of the human pelvis with the horse. Therefore this paper aims to
      study the interaction between horse and rider in professional riders (PRO) and
      beginners (BEG). Twenty riders rode in walk, trot, and canter in an indoor riding
      hall with inertial sensors attached to their pelvis and to the horses' trunk.
      Statistical analysis of waveform parameters, qualitative interpretation of angle
      angle plots, and cross-correlation of horse and rider were applied to the data.
      Significant differences between PRO and BEG could be found for specific waveform
      parameters. Over all gaits PRO kept their pelvis closer to the mid-position and
      further forward whereas BEG tilted their pelvis further to the right and more
      backwards. The coupling intensity of horse and rider revealed differences between
      the gaits. Furthermore phase shifts were found between PRO and BEG. This paper
      describes a sensor-based approach for the investigation of interactions of the
      human pelvis with the trunk of a horse under in-field conditions. First the
      results show that the riding level influences the posture of a rider and secondly
      that differences can be detected with contemporary available sensor technology
      and methods. 

PMID- 24290613
TI  - Leg stiffness: comparison between unilateral and bilateral hopping tasks.
AB  - Leg stiffness is a predictor of athletic performance and injury and typically
      evaluated during bilateral hopping. The contribution of each limb to bilateral
      leg stiffness, however, is not well understood. This study investigated leg
      stiffness during unilateral and bilateral hopping to address the following
      research questions: (1) does the magnitude and variability of leg stiffness
      differ between dominant and non-dominant legs? (2) Does unilateral leg stiffness
      differ from bilateral leg stiffness? and (3) Is bilateral leg stiffness
      determined by unilateral leg stiffness? Thirty-two physically active males
      performed repeated hopping tests on a force platform for each of the three
      conditions: bilateral hopping, unilateral hopping on the dominant leg, and
      unilateral hopping on the non-dominant leg. Leg stiffness was estimated as the
      ratio of the peak vertical force and the maximum displacement using a simple 1-D
      mass-spring model. Neither the magnitude nor variability of leg stiffness
      differed between dominant and non-dominant limbs. Unilateral leg stiffness was
      24% lower than bilateral stiffness and showed less variability between
      consecutive hops and subjects. Unilateral leg stiffness explained 76% of the
      variance in bilateral leg stiffness. We conclude that leg stiffness estimates
      during unilateral hopping are preferable for intervention studies because of
      their low variability. 

PMID- 24290614
TI  - The association of alcohol consumption and smoking with quality of life,
      disability and disease activity in an international sample of people with
      multiple sclerosis.
AB  - BACKGROUND: Modifiable lifestyle factors represent important targets for
      preventive intervention in multiple sclerosis (MS). We aimed to explore the
      association of cigarette smoking and alcohol consumption with major MS morbidity
      outcomes. METHODS: We surveyed a large, international sample of people with MS
      recruited via Web 2.0 platforms about type of MS, relapse rates, disability,
      disease activity, health-related quality of life (HRQOL), alcohol use and
      smoking. RESULTS: Of 2469 respondents with confirmed MS, 11.7% were current and
      40.3% former smokers. Most (61.5%) consumed less than 15 g alcohol weekly; few
      (0.8%) drank large amounts. Moderate alcohol consumption was associated with
      increased HRQOL; and after controlling for age and gender, was associated with
      lower odds of significant disability (41% decrease). After controlling for age,
      gender and alcohol use, smokers had an increased likelihood of major mobility
      requirements by 90% compared to never smokers. There was no association between
      alcohol or smoking and relapse rate or disease activity after controlling for age
      and gender, however among former smokers, a longer duration of smoking cessation
      was associated with reduced disease activity. Smokers had significantly lower
      HRQOL than never smokers and former smokers; heavier smoking was associated with
      greater decreases in HRQOL. CONCLUSION: This cross-sectional study supports
      previous research showing a link between morbidity indicators in MS and alcohol
      use and smoking. While people with MS should be advised of the potential risks of
      smoking, any risks and benefits of alcohol consumption require validation using a
      prospective cohort of people with MS.

PMID- 24290615
TI  - Abdominal obesity and low-grade systemic inflammation as markers of subclinical
      organ damage in type 2 diabetes.
AB  - AIM: This study aimed to explore the associations between abdominal obesity,
      inflammatory markers and subclinical organ damage in 740 middle-aged patients
      with type 2 diabetes. METHODS: Waist circumference (WC) and sagittal abdominal
      diameter (SAD) were measured, and blood samples were analyzed for C-reactive
      protein (CRP) and IL-6. Carotid intima-media thickness (IMT) was evaluated by
      ultrasonography, and aortic pulse wave velocity (PWV) measured with applanation
      tonometry. RESULTS: Abdominal obesity as determined by SAD and WC was
      significantly correlated with IL-6 (WC: r=0.27, P<0.001; SAD: r=031, P<0.001),
      CRP (WC: r=0.29, P<0.001; SAD: r=0.29, P<0.001), IMT (WC: r=0.09, P=0.013; SAD:
      r=0.11, P=0.003) and PWV (WC: r=0.18, P<0.001; SAD: r=0.21, P<0.001). In multiple
      linear regressions with IMT and PWV as dependent variables, and age, gender,
      statin use, systolic blood pressure (SBP), body mass index (BMI), CRP and HbA1c
      as independent variables, both SAD and WC remained associated with IMT and PWV.
      On stepwise linear regression and entering both SAD and WC, the association
      between SAD and PWV was stronger than the association between WC and PWV.
      CONCLUSION: Both SAD and WC are feasible measures of obesity, and both provide
      information on inflammation, atherosclerosis and arterial stiffness in type 2
      diabetes, while SAD appears to be slightly more robustly associated with
      subclinical organ damage than WC.

PMID- 24290616
TI  - Can RSScan footscan((r)) D3DTM software predict injury in a military population
      following plantar pressure assessment? A prospective cohort study.
AB  - BACKGROUND: Injury in initial military training is common with incidences from 25
      to 65% of recruits sustaining musculoskeletal injury. Risk factors for injury
      include extrinsic factors such as rapid onset of high volume training, but
      intrinsic factors such as lower limb biomechanics and foot type. Prediction of
      injury would allow more effective training delivery, reduce manpower wastage and
      improve duty of care to individuals by addressing potential interventions.
      Plantar pressure interpretation of footfall has been shown to reflect
      biomechanical intrinsic abnormality although no quantifiable method of risk
      stratification exists. OBJECTIVE: To identify if pressure plate assessment of
      walking gait is predictive of injury in a military population. METHOD: 200 male
      subjects commencing Naval Officer training were assessed by plantar pressure
      plate recording, of foot contact pressures. A software interpretation, D3DTM,
      stratified the interpretation to measure 4 specific areas of potential
      correction. Participants were graded as to high, medium and low risk of injury
      and subsequently followed up for injury through their basic training. RESULTS:
      Seventy two percent of all injuries were attributed to subjects in the high and
      medium risk of injury as defined by the risk categorization. 47% of all injuries
      were sustained in the high-risk group. Participants categorized in the high-risk
      group for injury were significantly more likely to sustain injury than in medium
      or low groups (p<0.001, OR 5.28 with 95% CI 2.88, 9.70). CONCLUSIONS: Plantar
      pressure assessment of risk for overuse lower limb injury can be predictive of
      sustaining an overuse injury in a controlled training environment.

PMID- 24290617
TI  - Development and preliminary testing of the Schizophrenia Hope Scale, a brief
      scale to measure hope in people with schizophrenia.
AB  - BACKGROUND: Hope has received attention as a central component of recovery from
      mental illness; however, most instruments measuring hope were developed outside
      the mental health field. To measure the effects of mental health programs on hope
      in people with schizophrenia, a specialized scale is needed. OBJECTIVE: This
      study examined the psychometric properties of the newly developed 9-item
      Schizophrenia Hope Scale (SHS-9) designed to measure hope in individuals with
      schizophrenia. DESIGN: A descriptive survey design. SETTING: Participants were
      recruited from three psychiatric hospitals and two community mental health
      centers in South Korea. PARTICIPANTS: A total of 347 individuals over age 18 with
      a DSM-IV diagnosis of schizophrenia, schizoaffective, or schizophrenia spectrum
      disorders (competent to provide written informed consent) participated in this
      study; 149 (94 men, 55 women) completed a preliminary scale consisting of 40
      revised items, and 198 (110 men, 88 women) completed the second scale of 17
      items. METHODS: Scale items were first selected from extensive literature reviews
      and a qualitative study on hope in people with schizophrenia; the validity and
      reliability of a preliminary scale was then evaluated by an expert panel and
      exploratory factor analysis. The remaining 9 items forming the Schizophrenia Hope
      Scale (SHS-9) were evaluated through confirmatory factor analysis. RESULTS: The
      SHS-9 demonstrates promising psychometric integrity. The internal consistency
      alpha coefficient was 0.92 with a score range of 0-18 and a mean total score of
      12.06 (SD=4.96), with higher scores indicating higher levels of hope. Convergent
      validity was established by correlating the SHS-9 to the State-Trait Hope
      Inventory, r=0.61 (p<0.01). Divergent validity with the Beck Hopelessness Scale
      was also established, r=-0.55 (p<0.01). Exploratory and confirmatory factor
      analysis resulted in a 1-factor solution, with the essential meaning of hope
      accounting for 61.77% of the total item variance. CONCLUSION: As hope has been
      shown to facilitate recovery from mental illness, the accurate assessment of hope
      provided by the short, easy-to-use Schizophrenia Hope Scale (SHS-9) may aid
      clinicians in improving the quality of life of individuals with schizophrenia.

PMID- 24290618
TI  - Medicine and medical sciences in Africa.
AB  - The year 2014 is an important year because it will mark the 25th Anniversary of
      the founding of the African Association of Physiological Sciences (AAPS) and
      initial talks to launch the International Society for Pathophysiology (ISP). Both
      these organizations had a foothold in Finland and both occurred during the IUPS
      Centennial Celebration Congress in 1989. The congress was hosted by the Finnish
      Physiological Society in Helsinki, Finland in July 1989. For both organizations,
      Prof OsmoHanninen was instrumental in the launching and inauguration of AAPS and
      also to initiate the creation of ISP. In order to celebrate the 25th
      Anniversaries of both organizations it was decided to hold the ISP2014 congress
      on the African soil. Hence in 2004, at the 4th international congress of AAPS
      held in Morocco, Wail Benjeloun.the then secretary general of AAPS, submitted
      successfully a bid to host ISP2014 in Morocco. Following the inauguration of AAPS
      in Helsinki, the 1st Congress of AAPS was held in Nairobi, Kenya in 1992 where
      the Constitution of AAPS was drawn up. The Constitution was adopted at the 2nd
      congress of AAPS in Durban, South Africa in 1997. Following this congress, the
      next congress, as scheduled, was held in Pretoria, South Africa in 2000. The last
      congress (6th) of AAPS was held on 1-5 September 2012 in Ismailia, Egypt. This
      was an historical congress because of many reasons and amongst these was the
      appointment of Anthony B. Ebeigbe, Department of Physiology, University of Benin,
      Nigeria as its first Editor-in-Chief of its official journal, the Journal of the
      African association of Physiological Sciences (JAAPS). He successfully published
      the first issue in June 2013, as mandated in Ismailia. The World's medicine has
      its initial root in Africa and in fact it was in Memphis, Egypt as early as 2700
      BC. During the Ptulomaic period the seat of medicine was in Alexandria, Egypt and
      Medical knowledge then spread to the Greeks 330 BC. Many western medical
      scientists acknowledge learning medicine and anatomy form the Egyptian experts.
      The University of Al Karaouine, in Fez, Morocco, Africa is considered the oldest
      continuously operating university in the world and has been a center of learning
      for more than 1,000 years. Medicine in Africa has been acknowledged by many
      authoritarians to be well developed, long before its development in Greece and
      other European Countries. Almost every African country has medical and medical
      sciences societies and associations. According the WHO, African journals online
      (AJOL) as the worlds largest collection of peer-reviewed journals. It is also
      believed that Africa will play a major role in Sciences in the future, and in
      fact one of the Worlds leading palaeo-anthropologist was a South African. 

PMID- 24290619
TI  - Diminution of 2,3,5-triphenyltetrazolium chloride toxicity on Listeria
      monocytogenes growth by iron source addition to the culture medium.
AB  - Tetrazolium salts (TTZ) such as 2,3,5-triphenyltetrazolium chloride (TTC) are
      readily reduced by bacterial populations of various genus. The reduced form of
      these redox indicators is conspicuously colored allowing a quick and easy
      detection of growth. The studies are mainly confined to Gram negative bacteria
      because of an important toxic effect of tetrazolium salts on Gram positive
      bacteria. Indeed, we observed an important impact of different tetrazolium salts
      on Listeria monocytogenes growth, curiously limited to an increase in the
      duration of the lag phase. In this study, we demonstrate that increasing the iron
      concentration in a medium containing TTC leads to a significant decrease of the
      lag phase. L. monocytogenes growth was kinetically measured and growth parameters
      were estimated using the Baranyi model. While lag phase diminution was found to
      be iron concentration dependent, growth rate was not affected. Addition of iron
      enables growth of some strains totally inhibited by a 0.4 g/l of TTC and for the
      other a significant reduction of the latency is observed. The nature of the
      mechanism resulting in a decrease of the observed lag phase remains unclear.
      Then, the use of iron supplementation may be proposed to overcome the inhibitory
      effect of TTC on L. monocytogenes. 

PMID- 24290620
TI  - Molecular characterization of antibiotic resistant Salmonella Typhimurium and
      Salmonella Kentucky isolated from pre- and post-chill whole broilers carcasses.
AB  - There is conflicting data regarding whether commercial chilling has any effect on
      persistence of Salmonella serovars, including antibiotic resistant variants, on
      chicken carcasses. A total of 309 Salmonella Typhimurium and Salmonella Kentucky
      isolates recovered from pre- and post-chill whole broiler carcasses were
      characterized for genetic relatedness using Pulsed Field Gel Electrophoresis
      (PFGE) and for the presence of virulence factors (invA, pagC, spvC) by PCR and
      for aerobactin and colicin production by bioassays. A subset of these isolates (n
      = 218) displaying resistance to either sulfisoxazole and/or ceftiofur [S.
      Typhimurium (n = 66) and S. Kentucky (n = 152)] were further tested for the
      presence of associated antibiotic resistance elements (class-I integrons and
      blaCMY genes) by PCR. All 145 ceftiofur resistant S. Kentucky and S. Typhimurium
      isolates possessed blaCMY genes. Class-I integrons were only detected in 6.1% (n
      = 4/66) of sulfisoxazole resistant S. Typhimurium isolates. The PFGE analysis
      revealed the presence of genetically diverse populations within the recovered
      isolates but clusters were generally concordant with serotypes and antimicrobial
      resistance profiles. At a 100% pattern similarity index, thirty-six percent of
      the undistinguishable S. Typhimurium and 22% of the undistinguishable S. Kentucky
      isolates were recovered from the same chilling step. All isolates possessed the
      invA and pagC genes, but only 1.4%possessed spvC. Irrespective of the chilling
      step, there was a significant difference (P < 0.05) in the production of
      aerobactin and colicin between S. Typhimurium and S. Kentucky isolates. Taken
      together, these results indicate that chilling impacted the recovery of
      particular Salmonella clonal groups but had no effect on the presence of class-I
      integrons, blaCMY genes, and tested virulence factors. 

PMID- 24290621
TI  - Effects of temperature on microbial succession and metabolite change during saeu
      jeot fermentation.
AB  - To investigate the effects of temperature on saeu-jeot (shrimp) fermentation,
      four sets of saeu-jeot samples with approximately 25% (w/v) NaCl were fermented
      at 10  degrees C, 15  degrees C, 20  degrees C, and 25  degrees C. The pH values
      of the 10  degrees C and 15  degrees C samples were relatively constant during
      the entire fermentation period, whereas those of the 20  degrees C and 25 
      degrees C samples gradually decreased after 25 days of fermentation. Quantitative
      PCR showed that the maximum bacterial abundance was greater in higher temperature
      samples, and the bacterial abundance in the 10  degrees C samples steadily
      decreased during the entire fermentation period. Community analysis using
      pyrosequencing revealed that the initially dominant Proteobacteria including
      Pseudoalteromonas, Photobacterium, Vibrio, Aliivibrio, and Enterovibrio were
      replaced rapidly with Firmicutes such as Psychrobacter, Staphylococcus,
      Salimicrobium, Alkalibacillus, and Halanaerobium as the fermentation progressed.
      However, Vibrio, Photobacterium, Aliivibrio, and Enterovibrio, which may include
      potentially pathogenic strains, remained even after 215 days in the 10  degrees C
      samples. Metabolite analysis using (1)H NMR showed that amino acid profiles and
      initial quick increases of glucose and glycerol were similar and independent of
      bacterial growth in all temperature samples. After 25 days of fermentation, the
      levels of glucose, glycerol, and trimethylamine N-oxide decreased with the growth
      of Halanaerobium and the increase of acetate, butyrate, and methylamines in the
      20  degrees C and 25  degrees C samples although the amino acid concentrations
      steadily increased until approximately 105 days of fermentation. Statistical
      triplot analysis showed that the bacterial successions occurred similarly
      regardless of the fermentation temperature, and Halanaerobium was likely
      responsible for the production of acetate, butyrate, and methylamines. This study
      suggests that around 15  degrees C might be the optimum temperature for the
      production of safe and tasty saeu-jeot. 

PMID- 24290622
TI  - Technological characterization and probiotic traits of yeasts isolated from
      Altamura sourdough to select promising microorganisms as functional starter
      cultures for cereal-based products.
AB  - The main topic of this research was to select some suitable functional starter
      cultures for cereal-based food or beverages. This aim was achieved through a step
      by step approach focused on the technological characterization, as well as on the
      evaluation of the probiotic traits of yeasts; the technological characterization
      relied on the assessment of enzymatic activities (catalase, urease, beta
      glucosidase), growth under various conditions (pH, temperature, addition of salt,
      lactic and acetic acids) and leavening ability. The results of this step were
      used as input data for a Principal Component Analysis; thus, the most
      technologically relevant 18 isolates underwent a second selection for their
      probiotic traits (survival at pH 2.5 and with bile salts added, antibiotic
      resistance, antimicrobial activity towards foodborne pathogens, hydrophobic
      properties and biofilm production) and were identified through genotyping. Two
      isolates (Saccharomyces cerevisiae strain 2 and S. cerevisiae strain 4) were
      selected and analyzed in the last step for the simulation of the gastric transit;
      these isolates showed a trend similar to S. cerevisiae var. boulardii ATCC MYA
      796, a commercial probiotic yeast used as control. 

PMID- 24290623
TI  - Identification of meat-associated pathogens via Raman microspectroscopy.
AB  - The development of fast and reliable sensing techniques to detect food-borne
      microorganisms is a permanent concern in food industry and health care. For this
      reason, Raman microspectroscopy was applied to rapidly detect pathogens in meat,
      which could be a promising supplement to currently established methods. In this
      context, a spectral database of 19 species of the most important harmful and non
      pathogenic bacteria associated with meat and poultry was established. To create a
      meat-like environment the microbial species were prepared on three different agar
      types. The whole amount of Raman data was taken as a basis to build up a three
      level classification model by means of support vector machines. Subsequent to a
      first classifier that differentiates between Raman spectra of Gram-positive and
      Gram-negative bacteria, two decision knots regarding bacterial genus and species
      follow. The different steps of the classification model achieved accuracies in
      the range of 90.6%-99.5%. This database was then challenged with independently
      prepared test samples. By doing so, beef and poultry samples were spiked with
      different pathogens associated with food-borne diseases and then identified. The
      test samples were correctly assigned to their genus and for the most part down to
      the species-level i.e. a differentiation from closely-related non-pathogenic
      members was achieved. 

PMID- 24290624
TI  - The Polymyxin Ceftazidime Oxford Medium as an alternative selective and
      differential medium for isolation of Listeria monocytogenes from raw or
      unpasteurized food.
AB  - The Polymyxin Ceftazidime Oxford Medium (PCOM) was developed to recover Listeria
      monocytogenes from raw or unpasteurized foods. It contains esculin-ferric
      ammonium citrate as indicator system for Listeria growth, and ceftazidime and
      polymyxin B as selective agents, which are available in several Latin American
      countries. Comparison of PCOM, Modified Oxford Medium (MOX) and Tryptic Soy agar
      with 0.6% yeast extract (TSAYE) indicated that both selective media were equally
      effective at recovering four individual strains of L. monocytogenes (Scott A, V7,
      California and broccoli), and a mixture of these strains (LMM) (P > 0.05). The
      ability of PCOM, MOX, TSAYE and TSAYE supplemented with 4% NaCl to recover heat,
      acid and freeze-damaged LMM was similar for all media (P > 0.05). The PCOM proved
      to be effective at isolating colonies of LMM from inoculated raw beef chunks,
      unpasteurized orange juice, cabbage, and Mexican-style cheese by direct plating
      and by the US Department of Agriculture's Food Safety and Inspection Service
      enrichment method. Differentiation of L. monocytogenes colonies was easier on
      PCOM than on MOX for foods with high levels of background microbiota. Based on
      the evaluations performed on foods naturally contaminated with L. monocytogenes,
      PCOM was a more economical alternative than MOX for selective and differential
      isolation of Listeria from raw or unpasteurized foods. 

PMID- 24290625
TI  - Modeling the growth of Listeria monocytogenes on cut cantaloupe, honeydew and
      watermelon.
AB  - A recent outbreak linked to whole cantaloupes underscores the importance of
      understanding growth kinetics of Listeria monocytogenes in cut melons at
      different temperatures. Whole cantaloupe, watermelon, and honeydew purchased from
      a local supermarket were cut into 10 +/- 1 g cubes. A four-strain cocktail of L.
      monocytogenes from food related outbreaks was used to inoculate fruit, resulting
      in ~10(3) CFU/10 g. Samples were stored at 4, 10, 15, 20, or 25  degrees C and L.
      monocytogenes were enumerated at appropriate time intervals. The square root
      model was used to describe L. monocytogenes growth rate as a function of
      temperature. The model was compared to prior models for Salmonella and
      Escherichia coli O157:H7 growth on cut melon, as well as models for L.
      monocytogenes on cantaloupe and L. monocytogenes ComBase models. The current
      model predicts faster growth of L. monocytogenes vs. Salmonella and E. coli
      O157:H7 at temperatures below 20  degrees C, and agrees with estimates from
      ComBase Predictor, and a corrected published model for L. monocytogenes on cut
      cantaloupe. The model predicts ~4 log CFU increase following 15 days at 5 
      degrees C, and ~1 log CFU increase following 6 days at 4  degrees C. The model
      can also be used in subsequent quantitative microbial risk assessments.

PMID- 24290626
TI  - Use of the modified Gompertz equation to assess the Stevia rebaudiana Bertoni
      antilisterial kinetics.
AB  - In order to assess the antibacterial activity of Stevia rebaudiana Bertoni
      (Stevia), Listeria innocua growth was characterized at 37  degrees C, in
      reference medium supplemented with a leaf infusion, a crude extract, and a
      steviol glycosides purified extract. Experimental data were fitted to the
      modified Gompertz model and the antibacterial activity of Stevia was determined
      based on the lag time (lambda) and the maximum growth rate (MUmax) reached,
      depending on the incubation conditions. As the leaf infusion showed the most
      marked elongation of lambda and the most marked MUmax reduction, its
      antimicrobial effect was evaluated at different concentrations, at 37, 22 and 10 
      degrees C. According to the results obtained, in general, the lower the
      temperature or the higher the Stevia concentration, the longer the lambda and the
      lower the MUmax, statistically significant being the effect of reducing
      temperature from 37 or 22 to 10  degrees C, the effect of increasing Stevia
      concentration from 0 or 0.5 to 1.5 or 2.5% (w/v), at 37  degrees C, and the
      elongation of lambda observed in presence of 1.5 and 2.5% (w/v) of Stevia, at 22 
      degrees C. These results show that Stevia could be a bacterial growth control
      measure if a cold chain failure occurs. 

PMID- 24290627
TI  - Genetic characterization of antibiotic resistance and virulence factors in
      Enterococcus spp. from Japanese retail ready-to-eat raw fish.
AB  - Little information is available on the diversity and distribution of resistance
      and virulence factors in enterococci isolated from retail fish. In this study,
      200 samples of retail ready-to-eat raw fish (sashimi) collected from the Japanese
      prefecture of Hiroshima were analyzed for incidence of Enterococcus spp. We
      recovered 96 enterococcal isolates from 90 (45%, 90/200) samples. Fifty-six
      strains were identified at the species level: E. faecalis (n = 31), E. faecium (n
      = 7), E. casseliflavus (n = 7), E. gallinarum (n = 3), E. phoeniculicola (n = 4),
      E. raffinosus (n = 2), E. saccharolyticus (n = 1), and E. gilvus (n = 1). Twenty
      five (26%, 25/96) strains carried antibiotic resistance genes. These included the
      tet(M), tet(L), tet(K), erm(B), msr(A/B), aph(3'), and blaZ genes, which were
      detected in 12.5%, 9.3%, 2%, 14.5%, 1%, 1%, and 2% of isolates, respectively. The
      virulence genes gelE and asa1 were detected in 31 and 24 E. faecalis strains,
      respectively. Both genes were detected in one E. faecium strain. In conclusion,
      this is the first study to underscore the importance of sashimi as not only a
      reservoir of Enterococcus spp. carrying resistance and virulence genes, but also
      a reservoir for unusual Enterococcus spp. 

PMID- 24290628
TI  - Isolation and molecular characterization of Salmonella enterica serovar
      Enteritidis from poultry house and clinical samples during 2010.
AB  - A total of 60 Salmonella enterica serovar (ser.) Enteritidis isolates, 28 from
      poultry houses and 32 from clinical samples, were isolated during 2010. These
      isolates were subjected to testing and analyzed for antibiotic resistance,
      virulence genes, plasmids and plasmid replicon types. To assess genetic
      diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting, using the XbaI
      restriction enzyme, Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA)
      and plasmid profiles were performed. All isolates from poultry, and 10 out of 32
      clinical isolates were sensitive to ampicillin, chloramphenicol, gentamicin,
      kanamycin, nalidixic acid, sulfisoxazole, streptomycin, and tetracycline. Twenty
      one of thirty-two clinical isolates were resistant to ampicillin and
      tetracycline, and one isolate was resistant to nalidixic acid. PFGE typing of
      sixty ser. Enteritidis isolates by XbaI resulted in 10-12 bands and grouped into
      six clusters each with similarity from 95% to 81%. The MLVA analysis of sixty
      isolates gave 18 allele profiles with the majority of isolates displayed in three
      groups, and two clinical isolates found to be new in the PulseNet national MLVA
      database. All isolates were positive for 12 or more of the 17 virulence genes
      mostly found in S. enterica (spvB, spiA, pagC, msgA, invA, sipB, prgH, spaN,
      orgA, tolC, iroN, sitC, IpfC, sifA, sopB, and pefA) and negative for one gene
      (cdtB). All isolates carried a typical 58 kb plasmid, type Inc/FIIA. Three
      poultry isolates and one clinical isolate carried small plasmids with 3.8, 6, 7.6
      and 11.5 kb. Ten of the clinical isolates carried plasmids, with sizes 36 and 38
      kb, types IncL/M and IncN, and one isolate carried an 81 kb plasmid, type IncI.
      Southern hybridization of a plasmid with an Inc/FIIA gene probe hybridized one
      large 58 kb plasmid in all isolates. Several large and small plasmids from
      poultry isolates were not typed by our PCR-based method. These results confirmed
      that PFGE fingerprinting has limited discriminatory power for ser. Enteritidis in
      both poultry and clinical sources. However, the plasmid and MLVA allele profiles
      were a useful and important epidemiology tool to discriminate outbreak strains of
      ser. Enteritidis from poultry and clinical samples. 

PMID- 24290629
TI  - Use of beta-cyclodextrin and activated carbon for quantification of Salmonella
      enterica ser. Enteritidis from ground beef by conventional PCR without
      enrichment.
AB  - The high level of PCR inhibitors present in ground beef is a major factor that
      affects molecular based techniques, such as the polymerase chain reaction (PCR),
      for the detection of Salmonella enterica. In this study, the use of beta
      cyclodextrin and milk protein coated activated carbon (MP-CAC) allowed the PCR to
      detect low numbers of Salmonella seeded into ground beef without enrichment of
      samples. invA was used as target gene in the conventional PCR protocol. With 25 g
      samples of ground beef containing 7.0, 15, and 27% fat, treatment of stomached
      samples with 5.0, 10, and 15% beta-cyclodextrin respectively followed by
      treatment with MP-CAC, resulted in the detection of 3 CFU/g (equivalent to 75 CFU
      in a 25 g sample). The total assay time was 4.5 h. The methodology described in
      this study for the detection of S. enterica in ground beef without enrichment is
      rapid, sensitive, and has the potential to be applied to a number of complex food
      matrices to detect low numbers of food-borne bacterial pathogens. 

PMID- 24290630
TI  - Multiplex variable number of tandem repeats for Oenococcus oeni and applications.
AB  - Oenococcus oeni is responsible for the malolactic fermentation of wine. Genomic
      diversity has already been established in this species. In addition, winemakers
      usually report varying starter-culture efficiency. It is essential to monitor
      indigenous and selected strains in order to understand strain survival and
      development during the winemaking process. A previous article described a
      variable number of tandem repeats (VNTR) scheme, based on five polymorphic loci
      of the genome. VNTR typing of O. oeni was highly discriminating, faster, and more
      reliable than the PFGE or MLST methods. The objective of this study was to set up
      a faster protocol by multiplexing, taking advantage of the high performance of
      multicolor capillary electrophoresis. The primers were labeled with multiple
      fluorescent dyes. PCR conditions were adapted by multiplexing amplifications in
      two separate PCR mixtures for the five loci, both at the same annealing
      temperature. The resulting assay proved to be robust, accurate, fast and easy to
      perform. Thanks to this new protocol, all O. oeni strains used in the study were
      typed using the five tandem repeats (TR). As expected, the primers for the five
      TR loci were specific to O. oeni. The method was improved to analyze isolated and
      mixed colonies, as well as bacteria harvested from wine using fast technology for
      analysis of nucleic acids (FTA((r))) technology. Finally, predictive models were
      constructed, to predict phylogenetic relationships and associate bacterial strain
      resistance to freeze-drying with fragment length analysis (FLA) profiles and
      genotypic and phenotypic characters. 

PMID- 24290631
TI  - Exposure of Escherichia coli O157:H7 to soil, manure, or water influences its
      survival on plants and initiation of plant defense response.
AB  - This study evaluated whether growth medium or exposure conditions influence the
      production of capsular polysaccharides (CPS) by Escherichia coli O157:H7, and
      whether changes in CPS impact plant defense responses, consequently affecting
      survival on plants. E. coli O157:H7 grown in Luria-Bertani (LB) broth
      supplemented with manure extracts showed an approximately 58% increase in CPS
      production compared to cells grown in LB medium alone. Levels of CPS were
      significantly higher for E. coli O157:H7 cells exposed to soil or manure extracts
      as compared to the non-exposed LB cultured control. Arabidopsis thaliana plants
      expressing beta-glucuronidase (GUS) under the control of the beta-1,3-glucanase
      (BGL2) promoter were used to investigate whether E. coli O157:H7 induces defense
      related gene expression. Plants inoculated with E. coli O157:H7 grown in LB
      containing manure extracts or cells exposed to manure extracts exhibited 3-fold
      and 2-fold lower GUS activity, respectively, suggesting a limited plant defense
      response compared to plants inoculated with cells grown in LB. On day 5 post
      inoculation the population of E. coli O157:H7 grown in LB supplemented with
      manure on plants was significantly greater than the population of E. coli O157:H7
      grown in LB medium alone. E. coli O157:H7 cells exposed to soil or manure
      exhibited greater survival on plants compared to LB-grown E. coli O157:H7. The
      results of this study underscore the need to consider medium composition and
      cultural conditions when conducting crop challenge studies. 

PMID- 24290632
TI  - Seasonal effects of heat shock on bacterial populations, including artificial
      Vibrio parahaemolyticus exposure, in the Pacific oyster, Crassostrea gigas.
AB  - During the warmer summer months, oysters are conditioned to spawn, resulting in
      massive physiological efforts for gamete production. Moreover, the higher
      temperatures during the summer typically result in increased bacteria populations
      in oysters. We hypothesized that these animals are under multiple stresses that
      lead to possible immune system impairments during the summer months that can
      possibly lead to death. Here we show that in the summer and the fall animals
      exposed to a short heat stress respond similarly, resulting in a general trend of
      more bacteria being found in heat shocked animals than their non-heat shocked
      counterparts. We also show that naturally occurring bacterial populations are
      effected by a heat shock. In addition, oysters artificially contaminated with
      Vibrio parahaemolyticus were also affected by a heat shock. Heat shocked animals
      contained higher concentrations of V. parahaemolyticus in their tissues and
      hemolymph than control animals and this was consistent for animals examined
      during summer and fall. Finally, oyster hemocyte interactions with V.
      parahaemolyticus differed based on the time of the year. Overall, these findings
      demonstrate that seasonal changes and/or a short heat shock is sufficient to
      impact bacterial retention, particularly V. parahaemolyticus, in oysters and this
      line of research might lead to important considerations for animal harvesting
      procedures. 

PMID- 24290633
TI  - Non-Botrytis grape-rotting fungi responsible for earthy and moldy off-flavors and
      mycotoxins.
AB  - The grape microflora is complex and includes filamentous fungi, yeasts and
      bacteria with different physiological characteristics and effects on wine
      production. Most studies have focused on the wine microbiota, but a few studies
      have reported the ecology of grape microorganisms. Some of these organisms - such
      as non-Botrytis bunch rotting fungi, which greatly influence the safety or
      sensory quality of wine, due to the production of mycotoxins and off-flavors,
      respectively - are considered to be spoilage agents. We review here the diversity
      of filamentous fungi on grapes and the factors influencing their development,
      such as grape ripening stage, environmental factors (climate, rain and
      cultivation practices), grape variety and grape health status. We also discuss
      the pathways by which mycotoxins and off-flavors are produced, the control of the
      population, the metabolites responsible for wine spoilage and the methods for
      detecting and characterizing the microorganisms involved. 

PMID- 24290634
TI  - Fate of Bacillus cereus and naturally occurring microbiota on milled rice as
      affected by temperature and relative humidity.
AB  - We studied the survival and growth patterns of Bacillus cereus, mesophilic
      aerobic bacteria (MAB), and molds and yeasts (MY) on rough and milled brown and
      white Korean rice stored at 12 and 21  degrees C and 43, 68, and 85% relative
      humidity (RH) for up to 24 wk. The initial populations of MAB present on rough
      rice, brown rice, and white rice were 7.7, 5.7, and 3.3 log CFU/g, respectively,
      and remained constant or decreased (P <= 0.05) by 0.7-1.8 log CFU/g during
      storage. The initial populations of B. cereus on the three types of laboratory
      inoculated rice were 3.1-3.8 log CFU/g and remained constant (P > 0.05) during
      storage, regardless of degree of milling, storage temperature, and RH. The
      initial populations of MY on rough rice, brown rice, and white rice were 6.2,
      4.2, and 2.1 log CFU/g, respectively. At 12  degrees C and 85% RH, the MY
      increased significantly (P <= 0.05) only on brown rice; however, at 21  degrees C
      and 85% RH, MY increased (P <= 0.05) on all types of rice during storage. These
      observations will be useful when assessing conditions affecting survival of B.
      cereus and determining environmental conditions necessary to prevent growth of
      potentially mycotoxigenic molds on various types of milled rice during storage. 

PMID- 24290635
TI  - Microbial decontamination of red pepper powder by cold plasma.
AB  - Effects of the microwave-powered cold plasma treatments (CPTs) on the inhibition
      of microorganisms in red pepper powder, including Aspergillus flavus and Bacillus
      cereus spores, were investigated. Combinations of heat treatment with CPT were
      investigated for the inhibition of B. cereus spores on the powder. The number of
      A. flavus was reduced by 2.5 +/- 0.3 log spores/g by the CPT with nitrogen at 900
      W and 667 Pa for 20 min. CPT at 900 W and 667 Pa for 20 min inhibited naturally
      occurring total aerobic bacteria in the red pepper powder by approximately 1 log
      CFU/g. B. cereus spores were inhibited (3.4 +/- 0.7 log spores/g reduction) only
      when heat treatment at 90  degrees C for 30 min was integrated with the CPT using
      a helium-oxygen gas mixture at 900 W. Fermi's model and Weibull model adequately
      described the inhibition of A. flavus on the red pepper powder by the CPT. The
      changes in treatment temperature and water activity were less than 5.0  degrees C
      (initial temperature: 23.8  degrees C) and 0.22, respectively, and were affected
      by both treatment power and time (P < 0.05). The CPTs have demonstrated the
      potential to reduce the microbial counts of red pepper powder and other powder
      products. 

PMID- 24290636
TI  - Effectiveness of a bacteriophage in reducing Listeria monocytogenes on fresh-cut
      fruits and fruit juices.
AB  - Listeria monocytogenes is a serious foodborne pathogen and new strategies to
      control it in food are needed. Among them, bacteriophages hold attributes that
      appear to be attractive. The objective of this study was to investigate the
      efficacy of the bacteriophage Listex P100 to control L. monocytogenes growth on
      melon, pear and apple products (juices and slices) stored at 10  degrees C. L.
      monocytogenes grew well in untreated fruit slices. In juices, the pathogen grew
      in untreated melon, survived in untreated pear and decreased in untreated apple.
      Phage treatment was more effective on melon followed by pear, but no effect on
      apple products was observed. Reductions of about 1.50 and 1.00 log cfu plug(-1)
      for melon and pear slices were found, respectively. In juices, higher reductions
      were obtained in melon (8.00 log cfu mL(-1)) followed by pear (2.10 log cfu mL(
      1)) after 8 days of storage. L. monocytogenes in apple juice was unaffected by
      phage treatment in which the phage decreased to almost undetectable numbers.
      These results highlight that Listex P100 could avoid pathogen growth on fresh-cut
      and in fruit juices with high pH during storage at 10  degrees C. The combination
      with other technologies may be required to improve the phage application on high
      acidity fruits. 

PMID- 24290637
TI  - Effects of pH and sugar concentration in Zygosaccharomyces rouxii growth and time
      for spoilage in concentrated grape juice at isothermal and non-isothermal
      conditions.
AB  - The effect of pH (1.7-3.2) and sugar concentration (64-68  degrees Brix) on the
      growth of Zygosaccharomyces rouxii MC9 using response surface methodology was
      studied. Experiments were carried out in concentrated grape juice inoculated with
      Z. rouxii at isothermal conditions (23  degrees C) for 60 days. pH was the
      variable with the highest effect on growth parameters (potential maximum growth
      rate and lag phase duration), although the effect of sugar concentration were
      also significant. In a second experiment, the time for spoilage by this
      microorganism in concentrated grape juice was evaluated at isothermal (23 
      degrees C) and non-isothermal conditions, in an effort to reproduce standard
      storage and overseas shipping temperature conditions, respectively. Results show
      that pH was again the environmental factor with the highest impact on delaying
      the spoilage of the product. Thereby, a pH value below 2.0 was enough to increase
      the shelf life of the product for more than 60 days in both isothermal and non
      isothermal conditions. The information obtained in the present work could be used
      by producers and buyers to predict the growth and time for spoilage of Z. rouxii
      in concentrated grape juice. 

PMID- 24290638
TI  - Analysis of the contrast between natural occurrence of toxigenic Aspergilli of
      the Flavi section and aflatoxin B1 in cassava.
AB  - Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin produced by Aspergilli of the
      section Flavi that may contaminate food, in the field or during storage. Cassava
      represents an important staple food in sub-Saharan Africa. The analysis of
      aflatoxigenic fungi in 36 cassava samples obtained from producers in Benin
      indicated that 40% were contaminated by Aspergilli of the section Flavi. Upon
      morphological and molecular characterization of the 20 isolates, 16 belonged to
      Aspergillus flavus, 2 to Aspergillus parvisclerotigenus and 2 to Aspergillus
      novoparasiticus. This is the first time that this latter species is isolated from
      food. Although most of these isolates were toxigenic on synthetic media, no AFB1
      contamination was observed in these cassava samples. In order to determine the
      action of cassava on AFB1 synthesis, a highly toxigenic strain of A. flavus, was
      inoculated onto fresh cassava and despite a rapid development, no AFB1 was
      produced. The anti-aflatoxin property was observed with cassava from different
      geographical origins and on other aflatoxigenic strains of the section Flavi, but
      it was lost after heating, sun drying and freezing. Our data suggest that fresh
      cassava is safe regarding AFB1 contamination, however, processing may alter its
      ability to block toxinogenesis leading to secondary contamination. 

PMID- 24290639
TI  - Yeast species and genetic heterogeneity within Debaryomyces hansenii along the
      ripening process of traditional ewes' and goats' cheeses.
AB  - The yeasts present during the ripening process of ewes' and goats' cheeses
      produced in a small traditional dairy in Mediterranean Spain were isolated and
      identified. Five hundred and thirty strains pertaining to eleven yeast species
      representing eight genera were identified using molecular methods. Debaryomyces
      hansenii was the yeast species most frequently isolated in all cheeses. Other
      yeast species commonly found in dairy products were present at the first maturing
      weeks. Two yeast species Trichosporon coremiiforme and Trichosporon domesticum
      have been reported in cheeses for the first time, and Meyerozyma guilliermondii
      has been newly isolated from goats' cheeses. Yeast species composition changed
      greatly along the process; although, D. hansenii dominated at the end of ripening
      in all cheeses. Most yeast isolates were able to hydrolyze casein and fatty acid
      esters. One hundred and eighty seven D. hansenii isolates were genotyped by PCR
      amplification of M13 satellites and an UPGMA dendrogram was constructed. The
      majority of isolates were grouped in 5 clusters while 7 profiles were represented
      by 1-3 isolates. These results demonstrate the genetic heterogeneity present in
      D. hansenii strains isolated from raw milk cheeses. 

PMID- 24290640
TI  - Brain is the predilection site of Toxoplasma gondii in experimentally inoculated
      pigs as revealed by magnetic capture and real-time PCR.
AB  - Pigs represent an important source of food in many countries, and undercooked
      pork containing tissue cysts is one of the most common sources of Toxoplasma
      gondii infection for humans. A magnetic capture method for the isolation of T.
      gondii DNA and quantitative real-time PCR targeting the 529 bp TOXO repeat
      element were used to estimate the parasite burden in different tissues of pigs
      experimentally infected with T. gondii oocysts, and to determine the predilection
      sites of T. gondii in this host species. The highest concentration of T. gondii
      DNA was found in brain tissues, equivalent to [median] 553.7 (range 3857.7-121.9)
      parasites per gram, followed by lungs, heart and dorsal muscles with median
      values corresponding to 0.3 (range 61.3-0.02); 2.6 (range 7.34-0.37) and 0.6
      (range 2.81-0.31) parasites per gram of tissue, respectively. Skeletal muscles
      from fore and hindlimb, liver and kidney presented very low infection burdens
      equivalent to [median] <=0.2 parasites per gram of tissues, and no parasite DNA
      could be detected in the spleen. This study contributes to understanding the
      value of different pig tissues as a source of T. gondii infection for humans and
      shows that the brain, while not being of major importance as human food source,
      may represent a first-line selection tissue when performing non-serological
      surveys (e.g. bioassays, histopathological, immunohistochemical or molecular
      studies) to detect T. gondii infections in pigs. 

PMID- 24290641
TI  - Sequence-based analysis of the bacterial and fungal compositions of multiple
      kombucha (tea fungus) samples.
AB  - Kombucha is a sweetened tea beverage that, as a consequence of fermentation,
      contains ethanol, carbon dioxide, a high concentration of acid (gluconic, acetic
      and lactic) as well as a number of other metabolites and is thought to contain a
      number of health-promoting components. The sucrose-tea solution is fermented by a
      symbiosis of bacteria and yeast embedded within a cellulosic pellicle, which
      forms a floating mat in the tea, and generates a new layer with each successful
      fermentation. The specific identity of the microbial populations present has been
      the focus of attention but, to date, the majority of studies have relied on
      culture-based analyses. To gain a more comprehensive insight into the kombucha
      microbiota we have carried out the first culture-independent, high-throughput
      sequencing analysis of the bacterial and fungal populations of 5 distinct
      pellicles as well as the resultant fermented kombucha at two time points.
      Following the analysis it was established that the major bacterial genus present
      was Gluconacetobacter, present at >85% in most samples, with only trace
      populations of Acetobacter detected (<2%). A prominent Lactobacillus population
      was also identified (up to 30%), with a number of sub-dominant genera, not
      previously associated with kombucha, also being revealed. The yeast populations
      were found to be dominated by Zygosaccharomyces at >95% in the fermented
      beverage, with a greater fungal diversity present in the cellulosic pellicle,
      including numerous species not identified in kombucha previously. Ultimately,
      this study represents the most accurate description of the microbiology of
      kombucha to date. 

PMID- 24290642
TI  - Microbiological, physico-chemical, nutritional and sensory characterization of
      traditional Matsoni: selection and use of autochthonous multiple strain cultures
      to extend its shelf-life.
AB  - Matsoni, a traditional Georgian fermented milk, has variable quality and
      stability besides a short shelf-life (72-120 h at 6  degrees C) due to inadequate
      production and storage conditions. To individuate its typical traits as well as
      select and exploit autochthonous starter cultures to standardize its overall
      quality without altering its typicality, we carried out a thorough physico
      chemical, sensorial and microbial characterization of traditional Matsoni. A
      polyphasic approach, including a culture-independent (PCR-DGGE) and two PCR
      culture-dependent methods, was employed to study the ecology of Matsoni. Overall,
      the microbial ecosystem of Matsoni resulted largely dominated by Streptococcus
      (S.) thermophilus and Lactobacillus (Lb.) delbrueckii subsp. bulgaricus. High
      loads of other lactic acid bacteria species, including Lb. helveticus, Lb.
      paracasei and Leuconostoc (Leuc.) lactis were found to occur as well. A selected
      autochthonous multiple strain culture (AMSC) composed of one Lb. bulgaricus, one
      Lb. paracasei and one S. thermophilus strain, applied for the pilot-scale
      production of traditional Matsoni, resulted the best in terms of enhanced shelf
      life (one month), sensorial and nutritional quality without altering its overall
      typical quality. This AMSC is at disposal of SMEs who need to exploit and
      standardize the overall quality of this traditional fermented milk, preserving
      its typicality. 

PMID- 24290643
TI  - Inhibition of Escherichia coli O157:H7 and Salmonella enterica on spinach and
      identification of antimicrobial substances produced by a commercial Lactic Acid
      Bacteria food safety intervention.
AB  - The microbiological safety of fresh produce is of concern for the U.S. food
      supply. Members of the Lactic Acid Bacteria (LAB) have been reported to
      antagonize pathogens by competing for nutrients and by secretion of substances
      with antimicrobial activity, including organic acids, peroxides, and
      antimicrobial polypeptides. The objectives of this research were to: (i)
      determine the capacity of a commercial LAB food antimicrobial to inhibit
      Escherichia coli O157:H7 and Salmonella enterica on spinach leaf surfaces, and
      (ii) identify antimicrobial substances produced in vitro by the LAB comprising
      the food antimicrobial. Pathogens were inoculated on freshly harvested spinach,
      followed by application of the LAB antimicrobial. Treated spinach was aerobically
      incubated up to 12 days at 7  degrees C and surviving pathogens enumerated via
      selective/differential plating. l-Lactic acid and a bacteriocin-like inhibitory
      substance (BLIS) were detected and quantified from cell-free fermentates obtained
      from LAB-inoculated liquid microbiological medium. Application of 8.0 log10 CFU/g
      LAB produced significant (p < 0.05) reductions in E. coli O157:H7 and Salmonella
      populations on spinach of 1.6 and 1.9 log10 CFU/g, respectively. It was concluded
      the LAB antimicrobial inhibited foodborne pathogens on spinach during
      refrigerated storage, likely the result of the production of metabolites with
      antimicrobial activity. 

PMID- 24290644
TI  - Investigating of yeast species in wine fermentation using terminal restriction
      fragment length polymorphism method.
AB  - The objective of this study was to examine the potential of terminal restriction
      fragment length polymorphism (T-RFLP) in monitoring yeast communities during wine
      fermentation and to reveal new information on yeast community of Chinese enology.
      Firstly, terminal restriction fragment (TRF) lengths database was constructed
      using 32 pure yeast species. Ten of these species were firstly documented. The
      species except for Candida vini, Issatchenkia orientalis/Candida krusei,
      Saccharomyces bayanus, Saccharomyces pastorianus, Saccharomyces cerevisiae,
      Saccharomyces kudriarzevii and Zygosaccharomyces bisporus could be distinguished
      by the T-RFLP targeting 5.8S-ITS rDNA. Moreover, the yeast communities in
      spontaneous fermentation of Chardonnay and Riesling were identified by T-RFLP and
      traditional methods, including colony morphology on Wallerstein Nutrient (WLN)
      medium and 5.8S-ITS-RFLP analysis. The result showed that T-RFLP profiles of the
      yeast community correlated well with that of the results identified by the
      traditional methods. The TRFs with the highest intensity and present in all the
      samples corresponded to Saccharomyces sp. Other species detected by both
      approaches were Hanseniaspora uvarum, Metschnikowia pulcherrima, Pichia minuta
      var. minuta, Saccharomycodes ludwigii/Torulaspora delbrueckii and Candida
      zemplinina. This study revealed that T-RFLP technique is a rapid and useful tool
      for monitoring the composition of yeast species during wine fermentation. 

PMID- 24290645
TI  - Inoculated fermentation of green olives with potential probiotic Lactobacillus
      pentosus and Lactobacillus plantarum starter cultures isolated from industrially
      fermented olives.
AB  - The performance of two strains of lactic acid bacteria (LAB), namely
      Lactobacillus pentosus B281 and Lactobacillus plantarum B282, previously isolated
      from industrially fermented table olives and screened in vitro for probiotic
      potential, was investigated as starter cultures in Spanish style fermentation of
      cv. Halkidiki green olives. Fermentation was undertaken at room temperature in
      two different initial salt concentrations (8% and 10%, w/v, NaCl) in the brines.
      The strains were inoculated as single and combined cultures and the dynamics of
      their population on the surface of olives was monitored for a period of 114 days.
      The survival of inoculated strains on olives was determined using Pulsed Field
      Gel Electrophoresis (PFGE). Both probiotic strains successfully colonized the
      olive surface at populations ranged from 6.0 to 7.0 log CFU/g throughout
      fermentation. PFGE analysis revealed that L. pentosus B281 presented higher
      colonization in both salt levels at the end of fermentation (81.2% and 93.3% in
      8% and 10% NaCl brines, respectively). For L. plantarum B282 a high survival rate
      (83.3%) was observed in 8% NaCl brines, but in 10% NaCl the strain could not
      colonize the surface of olives. L. pentosus B281 also dominated over L. plantarum
      B282 in inoculated fermentations when the two strains were used as combined
      culture. The biochemical profile (pH, organic acids, volatile compounds) attained
      during fermentation and the sensory analysis of the final product indicated a
      typical lactic acid fermentation process of green olives. 

PMID- 24290646
TI  - A microbial spoilage profile of half shell Pacific oysters (Crassostrea gigas)
      and Sydney rock oysters (Saccostrea glomerata).
AB  - This study aimed to assess bacterial spoilage of half shell Pacific and Sydney
      rock oysters during storage using microbial culture and 16S rRNA pyrosequencing.
      Odour and pH of oyster meats were also investigated. Estimation of
      microbiological counts by microbial culture highlighted growth of psychrotrophic
      bacteria. During storage, odour scores (a score describing deterioration of fresh
      odours where a score of 1 is fresh and 4 is completely spoiled) increased from
      1.0 to 3.0 for Pacific oysters and from 1.3 to 3.4 for Sydney rock oysters. pH
      results obtained for both species fluctuated during storage (range 6.28-6.73)
      with an overall increase at end of storage. Pyrosequencing revealed that the
      majority of bacteria at Day 0 represented taxa from amongst the Proteobacteria,
      Tenericutes and Spirochaetes that have not been cultured and systematically
      described. During storage, Proteobacteria became abundant with Pseudoalteromonas
      and Vibrio found to be dominant in both oyster species at Day 7. Analysis of the
      pyrosequencing data showed significant differences in bacterial profiles between
      oyster species and storage time (both P = 0.001). As oysters spoiled, bacterial
      profiles between oyster species became more similar indicating a common spoilage
      profile. Data presented here provides detailed insight into the changing
      bacterial profile of shucked oysters during storage and has identified two
      genera, Pseudoalteromonas and Vibrio, as being important in spoilage of shucked
      oysters. 

PMID- 24290647
TI  - Bacteriocinogenic potential and safety evaluation of non-starter Enterococcus
      faecium strains isolated from home made white brine cheese.
AB  - Four LAB strains, isolated from Bulgarian home made white brine cheese, were
      selected for their effective inhibition against Listeria monocytogenes. According
      to their biochemical and physiological characteristics, the strains were
      classified as members of Enterococcus genus, and then identified as Enterococcus
      faecium by 16S rDNA sequencing. Their bacteriocin production and inhibitory
      spectrum were evaluated together with the occurrence of several bacteriocin genes
      (entA, entB, entP, entL50B). Their virulence potential and safety was assessed
      both using PCR targeted to the genes gelE, hyl, asa1, esp, cylA, efaA, ace, vanA,
      vanB, hdc1, hdc2, tdc and odc and by phenotypical tests for antibiotic
      resistance, gelatinase, lipase, DNAse and alpha- and beta-haemolysis. The E.
      faecium strains harboured at least one enterocin gene while the occurrence of
      virulence, antibiotic resistance and biogenic amines genes was limited.
      Considering their strong antimicrobial activity against L. monocytogenes strains,
      the four E. faecium strains exhibited promising potential as bio-preservatives
      cultures for fermented food productions. 

PMID- 24290648
TI  - Tailoring the probiotic potential of non-starter Lactobacillus strains from
      ripened Parmigiano Reggiano cheese by in vitro screening and principal component
      analysis.
AB  - Non-starter lactic acid bacteria (NSLAB) inhabiting fermented food have been
      recently revised as source of probiotic strains. Here, we in vitro assessed the
      potential probiotic aptitude of a de-replicated set of NSLAB previously isolated
      from long ripened Parmigiano Reggiano cheeses (22 Lactobacillus rhamnosus, 18
      Lactobacillus paracasei, 3 Lactobacillus casei, 2 Lactobacillus harbinensis, and
      2 Lactobacillus fermentum). Most strains showed moderate to good resistance to
      biological barriers, including bile salts, lysozyme, and simulated gastric and
      pancreatic juices. Antimicrobial susceptibility tests against seven
      antimicrobials belonging to different categories showed that most strains are
      susceptible towards all the antibiotics, with the exception of vancomycin and
      streptomycin. The strains lost the streptomycin resistance when assayed on agar
      medium containing 0.5% bile salts, suggesting that detergent-like properties of
      cholic acids increase membrane permeability and mediate streptomycin
      susceptibility. No isolate showed bile salt hydrolase (BSH) activities,
      supporting that bile salts resistance and BSH activity are unpaired traits.
      Finally, NSLAB strains had moderate to high auto-aggregative and hydrophobic
      phenotypes, whereas two subsets of 22 and 8 strains co-aggregated with
      Escherichia coli and Salmonella enterica s. typhimurium, respectively. A
      multivariate analysis was effective to segregate one L. casei and two L.
      rhamnosus strains showing physiological characteristics compatible with probiotic
      properties. 

PMID- 24290649
TI  - Current and emerging technologies for rapid detection and characterization of
      Salmonella in poultry and poultry products.
AB  - Salmonella is the leading cause of foodborne illnesses in the United States, and
      one of the main contributors to salmonellosis is the consumption of contaminated
      poultry and poultry products. Since deleterious effects of Salmonella on public
      health and the economy continue to occur, there is an ongoing need to develop
      more advanced detection methods that can identify Salmonella accurately and
      rapidly in foods before they reach consumers. Rapid detection and identification
      methods for Salmonella are considered to be an important component of strategies
      designed to prevent poultry and poultry product-associated illnesses. In the past
      three decades, there have been increasing efforts towards developing and
      improving rapid pathogen detection and characterization methodologies for
      application to poultry and poultry products. In this review, we discuss molecular
      methods for detection, identification and genetic characterization of Salmonella
      associated with poultry and poultry products. In addition, the advantages and
      disadvantages of the established and emerging rapid detection and
      characterization methods are addressed for Salmonella in poultry and poultry
      products. The methods with potential application to the industry are highlighted
      in this review. 

PMID- 24290650
TI  - Transfer of foodborne pathogens during mechanical slicing and their inactivation
      by levulinic acid-based sanitizer on slicers.
AB  - This study investigated the degree of cross-contamination between deli foods and
      slicers by Listeria monocytogenes, Salmonella, and Escherichia coli O157:H7, and
      their inactivation by levulinic acid (LA) plus sodium dodecyl sulfate (SDS) on
      slicers. The transfer rate of pathogens at 5 locations on the contaminated
      slicers (scenario I) and on food slices (scenario II) was determined. The
      antimicrobial efficacy of the LA + SDS sanitizers applied either as a liquid or
      as foam at three concentrations (0.5% LA + 0.05% SDS, 1% LA + 0.1% SDS, and 2% LA
      + 0.5% SDS) was determined for decontamination of the pathogens on the slicers at
      21  degrees C. After slicing 10 slices, the pathogens recovered from slicer
      blades were significantly (P < 0.05) less than the recovery from some other
      contact locations (scenario I). With an initial inoculum at approximately 8.5 log
      CFU/blade, the populations of the pathogens transferred from blades to slices
      decreased logarithmically (R(2) > 0.9, scenario II). Contaminated slicer surfaces
      sprayed with 1% LA plus 0.1% SDS as a foam (45-55 psi) reduced within 1 min 6.0
      to 8.0 log CFU/blade of the pathogens. Results revealed that cross-contamination
      can occur between deli foods and slicers. Also, LA-based sanitizer applied as
      foam can be a useful treatment to remove microbial contamination on the slicers. 

PMID- 24290651
TI  - Inactivation of Bacillus sporothermodurans spores by nisin and temperature
      studied by design of experiments in water and milk.
AB  - Spores of Bacillus sporothermodurans are known to be a contaminant of dairy
      products and to be extremely heat-resistant. A central composite experimental
      design with three factors using response surface methodology was used to evaluate
      the effect of nisin (50-150 UI/mL), temperature (80-100  degrees C), and
      temperature-holding time (10-20 min) on the inactivation of B. sporothermodurans
      LTIS27 spores in distilled water, in skim milk and in chocolate milk. The
      experimental values were shown to be significantly in good agreement with the
      values predicted by the quadratic equation since the adjusted determination
      coefficients (Radj(2)) were around 0.97. By analyzing the response surfaces
      plots, the inactivation was shown to be higher in distilled water than in skim
      milk under all the conditions tested. Five-log cycle reductions of B.
      sporothermodurans spores were obtained after a treatment at 95  degrees C for 12
      min in presence of 125 UI of nisin/mL in distilled water or at 100  degrees C for
      13 min in presence of 134 UI of nisin/mL in skim milk or at 100  degrees C for 15
      min in presence of 135 UI of nisin/mL in chocolate milk. This study showed the
      efficiency of nisin (15-184 UI/mL) in combination with temperature (73-106 
      degrees C) to inactivate spores of B. sporothermodurans in milk. 

PMID- 24290652
TI  - Abiotic factors and their interactions influence on the co-production of
      aflatoxin B(1) and cyclopiazonic acid by Aspergillus flavus isolated from corn.
AB  - The objectives of this study were i) to determine the effects of the interactions
      of water activity, temperature and incubation time on the co-production of AFB1
      and CPA by isolates of Aspergillus flavus with different profile of mycotoxin
      production and ii) to identify the aW and temperature limiting conditions for the
      production of both mycotoxins. Fungi used in this study were selected because
      they belonged to different chemotypes: chemotype I (AFB1+/CPA+), III (AFB1+/CPA-)
      and IV (AFB1-/CPA+), respectively. Two culture media were used; Czapek yeast agar
      (CYA) and corn extract agar (CEM), at different incubated temperatures (10-40 
      degrees C) and aW levels (0.80-0.98). AFB1 and CPA production were analyzed after
      7, 14, 21 and 28 days of incubation. Significant differences were observed with
      respect to mycotoxin production depending on the media evaluated. The AFB1
      production occurred more favorably on CYA while the highest CPA concentrations
      were recorded on CEM. Within the range of aW evaluated in this study, 0.83 was
      the limiting level for both toxins production. The optimum conditions for AFB1
      production occurred at 0.96 aW and 30  degrees C after 21 days of incubation,
      regardless of the media and isolate. Although different amounts of toxins were
      produced in each medium, the limiting and optimum conditions for their production
      were similar in both. No differences in the response of the three isolates to the
      abiotic factors discussed were observed despite belonging to different
      chemotypes. The determination of the thresholds of mycotoxins co-production,
      especially in the case of data obtained with the corn extract medium can be
      useful to avoid the conditions conducive to co-occurrence of these mycotoxins in
      corn. 

PMID- 24290653
TI  - Cultivable microorganisms associated with honeys of different geographical and
      botanical origin.
AB  - In this study, the composition of the cultivable microbial populations of 38
      nectar honey and honeydew honey samples of different botanical and geographical
      origin were assessed. After growth in specific media, various colonies with
      different appearance were isolated and purified before phenotypic (morphological,
      physiological and biochemical traits) and genotypic [randomly amplified
      polymorphic DNA (RAPD), repetitive DNA elements-PCR (rep-PCR) and restriction
      fragment length polymorphism (RFLP)] differentiation. The identification was
      carried out by 16S rRNA gene sequencing for bacteria and, in addition to RFLP, by
      sequencing the D1/D2 region of the 26S rRNA gene for yeasts and the 5.8S-ITS rRNA
      region for filamentous fungi. The results showed the presence of 13 species of
      bacteria, 5 of yeasts and 17 of filamentous fungi; the species most frequently
      isolated were Bacillus amyloliquefaciens, Zygosaccharomyces mellis and
      Aspergillus niger for the three microbial groups, respectively. The highest
      microbial diversity was found in multifloral honeys. No correlation among the
      microbial species and the botanical/geographical origin was found, but some
      strains were highly adapted to these matrices since they were found in several
      samples of different origin. 

PMID- 24290654
TI  - Oenococcus oeni strain typification by combination of Multilocus Sequence Typing
      and Pulsed Field Gel Electrophoresis analysis.
AB  - Oenococcus oeni is usually the main lactic acid bacteria (LAB) responsible for
      conducting malolactic fermentation (MLF) in wines. Pulsed Field Gel
      Electrophoresis (PFGE) is one of the most common methods used to identify
      different genotypes among the wine LAB populations. Although PFGE is a powerful
      typing tool, it is time-consuming and its results are not easily exchangeable
      between laboratories so typing methods such as Multilocus Sequence Typing (MLST)
      have been developed. In this study, thirty O. oeni isolates from Rioja
      Tempranillo wines were characterized performing SfiI and ApaI PFGE and MLST with
      eight housekeeping genes. Using the latter technique, six new alleles have been
      described for five genes. PFGE was slightly more efficient than MLST because of
      the number of genotypes and of the index of diversity (ID) that each technique
      discriminated. This has been the first time that PFGE and MLST results have been
      combined to shape a unique dendrogram. Thus, the combination of results from both
      typing methods allowed the discrimination of twenty-two PFGE-ST genotypes showing
      the highest ID of these research (0.947). According to these results, the future
      application of the combination of PFGE and MLST results could be successful for
      reliable O. oeni strain typification. 

PMID- 24290655
TI  - Characterization of lactic acid bacteria isolated from infant faeces as potential
      probiotic starter cultures for fermented sausages.
AB  - A total of 109 lactic acid bacteria isolated from infant faeces were identified
      by partial 16S rRNA, cpn60 and/or pheS sequencing. Lactobacillus was the most
      prevalent genus, representing 48% of the isolates followed by Enterococcus (38%).
      Lactobacillus gasseri (21%) and Enterococcus faecalis (38%) were the main species
      detected. A further selection of potential probiotic starter cultures for
      fermented sausages focused on Lactobacillus as the most technologically relevant
      genus in this type of product. Lactobacilli strains were evaluated for their
      ability to grow in vitro in the processing conditions of fermented sausages and
      for their functional and safety properties, including antagonistic activity
      against foodborne pathogens, survival from gastrointestinal tract conditions
      (acidity, bile and pancreatin), tyramine production, antibiotic susceptibility
      and aggregation capacity. The best strains according to the results obtained were
      Lactobacillus casei/paracasei CTC1677, L. casei/paracasei CTC1678, Lactobacillus
      rhamnosus CTC1679, L. gasseri CTC1700, L. gasseri CTC1704, Lactobacillus
      fermentum CTC1693. Those strains were further assayed as starter cultures in
      model sausages. L. casei/paracasei CTC1677, L. casei/paracasei CTC1678 and L.
      rhamnosus CTC1679 were able to lead the fermentation and dominate (levels ca.
      10(8) CFU/g) the endogenous lactic acid bacteria, confirming their suitability as
      probiotic starter cultures. 

PMID- 24290656
TI  - Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in
      type 2 diabetes mellitus: an open-label, randomized controlled clinical trial.
AB  - BACKGROUND AIMS: The use of bone marrow mononuclear cells (BM-MNCs) has achieved
      great outcomes in clinical practice. We aim to evaluate the efficacy and safety
      of autologous BM-MNC infusion and hyperbaric oxygen therapy (HOT) in type 2
      diabetes mellitus. METHODS: This single-center, randomized, open-label,
      controlled clinical trial with a factorial design included two phases. The
      patients received standard medical therapy in the run-in phase; in the treatment
      phase, patients with glycated hemoglobin of 7.5-9.5% were randomly assigned into
      four groups and underwent BM-MNC infusion along with HOT (BM-MNC+HOT group), BM
      MNC infusion (BM-MNC group), HOT (HOT group) and standard medical therapy
      (control group), respectively. The area under the curve of C-peptide was recorded
      as a primary end point. Our research is registered at ClinicalTrials.gov
      (NCT00767260). RESULTS: A total of 80 patients completed the follow-up. At 12
      months after treatment, the area under the curve of C-peptide (ng/mL per 180 min)
      of the BM-MNC+HOT group and the BM-MNC group were significantly improved (34.0%
      and 43.8% from the baseline, respectively). The changes were both significant
      compared with that in the control group, but no remarkable change was observed in
      the HOT group. Treatment-related adverse events were mild, including transient
      abdominal pain (n = 5) and punctual hemorrhage (n = 3). CONCLUSIONS: BM-MNC
      infusion for type 2 diabetes mellitus improves islet function and metabolic
      control, with mild adverse effects. HOT does not synergize with BM-MNC infusion.

PMID- 24290657
TI  - Tau hyperphosphorylation: a downstream effector of isoflurane-induced
      neuroinflammation in aged rodents.
AB  - Postoperative cognitive dysfunction (POCD) is a severe neurological sequela after
      anesthesia and surgery. Multiple risk factors, such as advanced age and
      anesthesia duration, relevant to POCD have been made out, although the
      pathophysiological mechanisms of this complication need to be further elucidated.
      To date, there is a substantial body of evidence implicating that
      neuroinflammatory cytokines and the subsequent neuroinflammatory response
      contribute to the cognitive impairment in aged rodents exposed to isoflurane, a
      commonly used general anesthetic. Interestingly, this cognitive disorder is
      mitigated by anti-inflammatory agents even 14 days after isoflurane exposure. In
      addition, isoflurane-induced upregulation of neuroinflammatory cytokines is only
      limited within 48 h. So a first possibility to consider is a downstream effector
      of isoflurane-induced neuroinflammatory cytokines which contributes to the long
      lasting cognitive dysfunction. In Alzheimer's disease (AD) models,
      proinflammatory cytokines can induce tau hyperphosphorylation which is associated
      with synaptic abnormality and further cognitive impairment. It is unknown whether
      isoflurane-induced neuroinflammatory cytokines can trigger tau
      hyperphosphorylation. Taken together, we hypothesize that tau
      hyperphosphorylation is a downstream target of isoflurane-induced
      neuroinflammatory response and thus bridges the isoflurane-induced relatively
      transient neuroinflammatory process to the long-term cognitive impairment.

PMID- 24290658
TI  - Can we prevent premature luteinization in IVF cycles?
AB  - From 1991 there is a long-lasting discussion on a possible detrimental effect of
      premature increase of progesterone levels during ovarian stimulation in IVF. A
      recent meta-analysis of more than 60,000 cycles states that premature
      progesterone increase reduces pregnancy rates starting from P4 values of 0.8
      ng/ml. The detrimental effect seems to be related to endometrial receptivity
      impairment according to lack of detrimental effect on oocytes competence in
      ovodonation. Embryo freezing and deferred embryo transfer on artificial
      endometrium permits to avoid this detrimental effect but the cycle has to be
      segmented in two phases. Moreover embryo freezing is an extra burden for IVF lab
      and could induce embryo damage. So the implementation of an effective
      pharmacological treatment to prevent premature luteinization could be very
      interesting for our daily ART practice. On the basis of so far available
      literature data and our preliminary proof of concept experience we suggest that
      metformin (1000-1500 mg daily) from first monitoring until ovulation triggering
      could be suitable for this purpose irrespective of ovarian reserve of the
      patient.

PMID- 24290659
TI  - Excimer Laser LEsion modification to expand non-dilatable stents: the ELLEMENT
      registry.
AB  - BACKGROUND/OBJECTIVES: Stent underexpansion is a risk factor for in-stent
      restenosis and stent thrombosis. Existing techniques to optimize stent expansion
      are sometimes ineffective. The aim of this study was to evaluate the
      effectiveness and feasibility of Excimer Laser Coronary Angioplasty (ELCA) in
      improving stent expansion when high-pressure non-compliant balloon inflation was
      ineffective. METHODS AND RESULTS: ECLA ablation was performed at high energy
      during contrast injection and only within the underexpanded stent. The primary
      endpoint of successful laser dilatation was defined as an increase of at least
      1mm(2) in minimal stent cross-sectional area (MSA) on IVUS or an increase of at
      least 20% in minimal stent diameter (MSD) by QCA, following redilatation with the
      same non-compliant balloon that had been unsuccessful prior to ELCA. Secondary
      endpoints were cardiac death, myocardial infarction (MI) and target lesion
      revascularization. Between June 2009 and November 2011, 28 patients with an
      underexpanded stent despite high-pressure balloon inflation were included. The
      mean laser catheter size was 1.2+/-0.4 (range 0.9-2.0mm) and a mean of 62+/
      12mJ/mm(2) at 62+/-21hertz were required for optimal expansion. Laser-assisted
      stent dilatation was successful in 27 cases (96.4%), with an improvement in MSD
      by QCA (1.6+/-0.6mm at baseline to 2.6+/-0.6mm post-procedure) and MSA by IVUS
      (3.5+/-1.1mm(2) to 7.1+/-1.9mm(2)). Periprocedural MI occurred in 7.1%, transient
      slow-flow in 3.6% and ST elevation in 3.6%. During follow-up, there were no MIs,
      there was 1 cardiac-death, and TLR occurred in 6.7%. CONCLUSIONS: The ELLEMENT
      study confirms the feasibility of ELCA with contrast injection to improve stent
      underexpansion in undilatable stented lesions.

PMID- 24290660
TI  - Child and family-level correlates of direct and indirect peer victimization among
      children ages 6-9.
AB  - The purpose of this study was to examine the prevalence and child and family
      level correlates of direct and indirect victimization by peers among children
      ages 6-9. Four hundred and twenty-five children were included in the final
      sample. Data for this study were drawn from the first wave of the Developmental
      Victimization Survey. Logistic regression models were used to examine
      associations between children's demographics, anxiety, depression, anger, parent
      child relationship, and exposure to family violence and children's experience of
      direct or indirect victimization by peers. The results showed that increased
      depression scores and exposure to family violence were associated with increased
      risk for direct and indirect victimization by peers. Black children were more
      likely to experience direct victimization and less likely to experience indirect
      victimization compared to White children. Child's race significantly moderated
      the association between parental criticism and indirect victimization. Child's
      gender did not significantly moderate these associations. Implications for
      developmentally specific prevention and intervention approaches that are grounded
      in a social-ecological framework are discussed. 

PMID- 24290661
TI  - Adult haemophagocytic syndrome.
AB  - Haemophagocytic syndromes (haemophagocytic lymphohistiocytosis) have a wide range
      of causes, symptoms, and outcomes, but all lead to a hyperinflammatory response
      and organ damage--mainly reported in paediatric patients, but reports of adult
      presentation are increasing. Analysis of the genetic and molecular
      pathophysiology of these syndromes have improved the understanding of the
      crosstalk between lymphocytes and histiocytes and their regulatoty mechanisms.
      Clinical presentations with a broad differential diagnosis, and often life
      threatening outcome, complicate the management, which might include supportive
      intensive care, immunosuppressive and biological treatments, or haemopoietic stem
      cell transplantation. Insufficient knowledge of these syndromes could contribute
      to poor prognosis. Early diagnosis is essential to initiate appropriate treatment
      and improve the quality of life and survival of patients with this challenging
      disorder.

PMID- 24290662
TI  - Growth regulation, imprinting, and epigenetic transcription-related gene
      expression differs in lung of deceased transgenic cloned and normal goats.
AB  - Somatic cell nuclear transfer (SCNT) is a promising technique to produce
      mammalian transgenic clones. Only a small proportion of manipulated embryos,
      however, can develop into viable offspring. The abnormal growth and development
      of cloned animals, furthermore, are accompanied by aberrant lung development. Our
      objective was to investigate molecular background of lung developmental problems
      in transgenic (random insertion of exogenous DNA) cloned goats. We examined
      expression of 15 genes involved in growth regulation, imprinting, and epigenetic
      transcription in lung tissue of deceased transgenic cloned and normal goats of
      various ages. Compared with normal goats of the same age from conventional
      reproduction, expression of 13 genes (BMP4, FGF10, GHR, HGFR, PDGFR, RABP, VEGF,
      H19, CDKNIC, PCAF, MeCP2, HDAC1, and Dnmt3b) decreased in transgenic cloned goats
      that died at or shortly after birth; Expression of eight genes (FGF10, PDGFR,
      RABP, VEGF, PCAF, HDAC1, MeCP2, and Dnmt3b) decreased in fetal death of
      transgenic cloned goats. Expression of two epigenetic transcription genes (PCAF
      and Dnmt3b) decreased in disease death of transgenic cloned goats (1-4 months
      old). Disruptions in gene expression might be associated with the high neonatal
      mortality in transgenic cloned animals. These findings have implications in
      understanding the low efficiency of transgenic cloning.

PMID- 24290663
TI  - [External quality assurance].

PMID- 24290664
TI  - [Requirements for quality indicators. The relevance of current developments in
      outcomes research for quality management].
AB  - The assessment of the health state in patients and changes in their health state
      for the purpose of diagnosis, prognosis and monitoring of treatment response
      plays a central role in clinical practice. Quality criteria for measurements in
      medicine include validity, reliability, responsiveness, interpretability, and
      feasibility. High-quality measurement instruments are a prerequisite for evidence
      based medicine. Therefore, international outcomes research groups have developed
      methods for quality assurance and for the standardisation of measurement
      instruments. Quality indicators are instruments to measure the quality of care.
      Due to the increasing relevance of quality assessment for all stakeholders in
      healthcare and due to the political intention to draw relevant conclusions from
      the assessment of the quality of care, quality indicators must at least meet the
      same high standards that are required for clinical trial end points. However,
      independent researchers and clinicians do not engage in the validation and
      standardisation of quality indicators in Germany; currently, only the AQUA
      institute (as assigned by the German GBA) deals with this important issue.
      Current activities concerning the validation of quality indicators do not meet
      the requirements of evidence-based healthcare. This is a critical barrier to
      achieving the political goals of quality medicine. Therefore, the authors propose
      a multi-step, multi-professional, evidence-driven and evidence-generating
      consensus process on the basis of established methods of outcomes research for
      the advancement of quality assessment with quality indicators in Germany. All
      relevant stakeholders should participate in this process. 

PMID- 24290665
TI  - [Current challenges of external quality assurance in the German healthcare
      system].
AB  - External quality assurance has three main aims: to make service provision in
      medicine and nursing comparable, to systematically identify deficits in service
      quality and to support the introduction of measures for quality improvement. This
      article reflects on three major developments in mandatory external quality
      assurance in the German healthcare system that took place during the last five
      years. These developments include the implementation of cross-sectoral quality
      assurance, the utilisation of new data sources and a new focus on quality
      deficits and practicability. The article highlights the challenges that come
      along with these developments. 

PMID- 24290666
TI  - [Cross-sectoral quality assurance in ambulatory care].
AB  - Overcoming rigid sectoral segmentation in healthcare has also become a health
      policy target in quality assurance. With the Act to Enhance Competition in
      Statutory Health Insurance (GKV-WSG) coming into effect, quality assurance
      measures are to be designed in a cross-sectoral fashion for in- and outpatient
      sectors equally. An independent institution is currently mandated to develop
      specific quality indicators for eleven indications. For three of these operating
      tests have already been commissioned by the Federal Joint Committee. This article
      depicts the major results of a feasibility study, including a compliance cost
      estimate, for the aforementioned indications of cross-sectoral quality assurance
      (cQA). In conclusion, a number of both practical and conceptual basic challenges
      are still to be resolved prior to the full implementation of cQA, such as a
      sufficient specification to activate documentation requirements and an inspection
      system capable of separating actual quality problems from documentary deficits.
      So far, a comprehensive cost-utility analysis of cQA has not been provided, in
      particular with comparison to existing QA systems. In order to optimise cost and
      utility of cQA an evidence-based approach is required for both the extension of
      cQA areas and for QA provisions. 

PMID- 24290667
TI  - [Potentials of cooperative quality management initiatives: BQS Institute
      projects, January 2010 - July 2013].
AB  - Alongside the projects of internal quality management and mandatory quality
      assurance there is a variety of quality driven projects across institutions
      initiated and run by various partners to continuously improve the quality of
      care. The multiplicity and characteristics of these projects are discussed on the
      basis of projects run by the BQS Institute between 2010 and 2013. In addition,
      useful interactions and linking with mandatory quality benchmarking and with
      internal quality management are discussed. (As supplied by publisher). 

PMID- 24290668
TI  - [Evaluation of external quality assurance in accordance with sect. 137 SGB V at
      the Carl Gustav Carus university hospital in Dresden].
AB  - BACKGROUND: Obligatory external quality assurance is an established method used
      to ensure the quality of inpatient care in Germany. The comprehensive approach is
      unique in international comparison. In addition to the statutory requirement, the
      health insurance funds require this form of external quality control in order to
      foster quality-based competition between hospitals. Ever since its introduction,
      healthcare providers have scrutinised the effects of the mandatory use of this
      survey. METHOD AND MATERIALS: The study was based on all patients in the
      University Hospital Dresden, for whom a quality assurance sheet (n = 45,639) had
      to be recorded between 2003 and 2011. The documentation of these sheets was
      carried out by specially trained personnel. For each performance area, the
      duration of the documentation quality sheets was assessed, and a descriptive
      analysis of all quality assurance sheets was conducted. In the presence of
      statistical significance the so-called "Structured Dialogues" were analysed.
      RESULTS: Over the whole period, 167 statistically noticeable problems occurred.
      Nine of these have been rated as noticeable problems in medical quality by the
      specialised working groups of the project office quality assurance (PGSQS) at the
      Saxon State Medical Association (SLAK). The remaining 158 statistical anomalies
      included 25 documentation errors; 96 were classified as statistically
      significant, and only 37 were marked to indicate that re-observation by the PGSQS
      was required. The total effort estimate for the documentation of quality
      assurance sheets was approximately 1,420 working days in the observation period.
      DISCUSSION: As far as the quality of patient care is concerned, the results can
      be considered positive because only a small number of quality indicators indicate
      noticeable qualitative problems. This statement is based primarily on the
      comparison of the groups of Saxony and Germany, which are included in the quality
      report of external quality assurance in accordance with sect. 137 SGB V. The
      majority of noticeable statistical problems were due to documentation errors.
      Other noticeable statistical problems that are medically indicated, but without
      effect on the extramural care to patients, recurrently occur with the respective
      quality indicators. Examples include the postoperative mobility indicators of the
      implementation of endoprostheses which cannot be used to draw conclusions about
      patient outcomes. Information on the quality of life as well as the post-hospital
      course of disease would be important in this context, but is still lacking. The
      use of external quality assurance data in accordance with sect. 137 SGB V for
      evaluation research has so far been handled quite restrictively. Thus, in-depth
      analyses on the quality of treatment cannot be derived.

PMID- 24290670
TI  - [Transferability of patient safety indicators to the German hospital setting:
      results of a Delphi survey].
AB  - AIM: To assess the transferability of 14 evidence-based patient safety indicators
      (PSI) to the German hospital system. METHODS: A two-staged modified
      multidisciplinary Delphi process was used, applying the scientific criteria of
      the QUALIFY instrument. RESULTS: Eleven of the 14 PSI were judged to be
      transferable to and feasible in the German hospital setting. CONCLUSIONS: The
      consented PSI are potentially suitable for German quality assurance measurement.
      Prior to implementation, further operationalisation and empirical validation is
      recommended.

PMID- 24290669
TI  - [WINHO quality indicators for outpatient oncology care in Germany].
AB  - The aim of the WINHO indicators project is to describe and enhance the quality of
      outpatient oncology care in Germany with indicators. This paper deals with the
      development of a set of evidence- and consensus-based meaningful indicators to
      assess the quality of outpatient oncology care in Germany. These indicators are
      intended to be applied in assessments of quality of patient care in oncology
      practices, in quality reports and in peer-to-peer benchmarking. A set of 272
      already existing indicators was identified through internet and literature
      searches. After redundancy reduction and addition of newly developed indicators
      for areas of ambulatory oncology care that were not yet covered, a preliminary
      set of 67 indicators was established. The further development of the indicator
      set was based on a modified version of the two-step RAND/UCLA expert evaluation
      method, which has been internationally established for developing quality
      indicator sets. The indicators were modified after the first round of ratings.
      After completing and assessing the second round of ratings, a set of 46
      homogeneously positively rated quality indicators is now available for outpatient
      oncology care in Germany. 

PMID- 24290671
TI  - Fatal bleeding due to acquired factor IX and X deficiency: a rare complication of
      primary amyloidosis; case report and review of the literature.

PMID- 24290672
TI  - Comparison of dietary intake among women on maintenance dialysis to a Women's
      Health Initiative cohort: results from the NKF-CRN Second National Research
      Question Collaborative Study.
AB  - OBJECTIVE: The objective of this study was to compare the characteristics and
      dietary intake of Second National Research Question (SNRQ) participants to the
      Women's Health Initiative-Dietary Modification (WHI-DM) Trial group and to
      compare the dietary intake of both groups to relevant reference norms. DESIGN:
      The study design was a secondary analysis of data collected from the SNRQ and
      from the WHI-DM Trial. SUBJECTS: SNRQ participants were adult women on dialysis
      (n = 248) from U.S. dialysis facilities. WHI-DM Trial participants (n = 48,836)
      were postmenopausal, 50- to 79-year-old women from 40 U.S. clinical centers.
      METHODS: The 1-sample t test, chi(2), and Wilcoxon signed-rank test were used to
      compare the SNRQ participants to the WHI-DM group and to compare the dietary
      intake of both to nutrition reference norms. Differences were considered
      significant at a 2-tailed P <= .01. MAIN OUTCOME MEASURE: Dietary intake was
      defined as dietary energy intake (DEI), dietary protein intake (DPI), fiber, fat,
      saturated fat, sodium, potassium, phosphorus, fruits, and vegetables. RESULTS:
      Characteristics including age, race, weight, educational level, and
      cardiovascular disease differed between the SNRQ and WHI-DM groups (P < .001).
      SNRQ participants had lower DEI, DPI, fiber, fat, saturated fat, potassium,
      sodium, phosphorus, fruit, and vegetable intake than WHI-DM women (P < .001).
      Dietary intake of SNRQ hemodialysis (HD) and peritoneal dialysis (PD) patients
      differed significantly from reference norms (P < .001) except for phosphorus
      intake in PD patients (P = .03). WHI-DM women had higher intakes of fat and
      saturated fat and lower intakes of fiber, fruit, and vegetables than recommended
      in reference norms for the general population. CONCLUSION: Dietary intake
      differed significantly between SNRQ participants and the WHI-DM group. Dietary
      intake of the SNRQ participants, except for phosphorus intake in PD patients,
      differed significantly from relevant reference norms.

PMID- 24290673
TI  - Occurrence, serotype diversity, and antimicrobial resistance of salmonella in
      ground beef at retail stores in Jalisco state, Mexico.
AB  - The occurrence, serotype diversity, and antimicrobial resistance of Salmonella
      bacteria in commercial ground beef at retail establishments were investigated.
      Salmonella was isolated from 135 (56.7%) of 238 ground beef samples collected at
      the same number of butcher's shops located in three municipalities of Jalisco
      State, Mexico, during an 11-month period. The isolation frequency differed by
      municipality (P < 0.05) and was higher (P < 0.05) during the warm season (68.5%)
      than during the cold season (43.2%). Overall, 25 serotypes and 8 serogroups were
      identified among 135 Salmonella isolates; predominant were Salmonella group B
      (9.6%), Salmonella Anatum (8.9%), Salmonella Agona (6.7%), Salmonella Infantis
      (6.7%), and Salmonella Typhimurium (5.9%). All Salmonella isolates were tested
      for susceptibility to 11 antimicrobial drugs of human and veterinary use.
      Resistance to tetracycline was the most commonly observed (40.7%), followed by
      resistance to streptomycin (35.6%), trimethoprim-sulfamethoxazole (20.7%), and
      nalidixic acid (19.3%). Thirty-seven Salmonella isolates (27.4%) were multidrug
      resistant, and the majority corresponded to Salmonella Group B, Salmonella
      Anatum, and Salmonella Typhimurium. Three Salmonella isolates were resistant to
      seven different antimicrobials. The frequency of Salmonella in ground beef
      samples (56.7%) was higher than that observed in our previous investigation on
      beef carcasses (15.4%) at small abattoirs in the same region of Mexico. This may
      be a result of increasing contamination at these two points of the raw-beef
      production chain or may be an effect of the grinding process that facilitates a
      more-homogeneous pathogen distribution in the product. Poor hygiene, temperature
      abuse, and practices allowing cross-contamination during ground beef fabrication
      at these retail establishments increase the consumer's exposure to Salmonella. 

PMID- 24290674
TI  - Antimicrobial susceptibility and serovars of salmonella circulating in commercial
      poultry carcasses and poultry products in Brazil.
AB  - Antimicrobial resistance was evaluated for 12,582 strains of Salmonella isolated
      by public and private laboratories from commercial poultry carcasses and poultry
      products from different regions in Brazil between 2007 and 2011. These isolates
      were submitted unsolicited to the National Reference Laboratory for Bacterial
      Enteroinfections, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de
      Janeiro, Brazil, for conclusive antigenic characterization. The prevalent
      Salmonella enterica serogroups were O:4 (B) (28.9%), O:9 (D1) (22.3%), O:21 (L)
      (15.9%), and O:7 (C1) (14.3%); the most prevalent serovars were Enteritidis,
      Minnesota, Typhimurium, Schwarzengrund, and Mbandaka. The antimicrobial
      susceptibility profiles of 1,234 strains indicated that 54.5% were resistant to
      up to eight antimicrobial drugs. Multidrug resistance (three or more classes) was
      observed in 16.4% of the strains, with 190 distinct patterns. The results showed
      increased resistance to ampicillin (12.4 to 18.9%), tetracycline (~ 15.2 to ~
      18.9%), and gentamicin (f7.0 to ~ 9.6%) during the study period. Decreased
      resistance to nitrofurans (61.9 to 9.2%), quinolones (44.4 to 15.5%), and folate
      inhibitors (11.7 to 7.2%) was observed. Resistance to third-generation
      cephalosporins was detected in 5.5% of the strains throughout the study period;
      resistance to fluoroquinolones has been observed in 0.3% of the strains since
      2009. These findings highlight the importance of surveillance along the food
      chain for detection of altered patterns among foodborne zoonotic bacteria that
      are important to public health. 

PMID- 24290675
TI  - Comparison of plasmids coharboring 16s rrna methylase and extended-spectrum beta
      lactamase genes among Escherichia coli isolates from pets and poultry.
AB  - A total of 247 Escherichia coli isolates (148 from diseased or dead poultry and
      99 from diseased pets in the People's Republic of China) were screened for
      extended-spectrum beta-lactamase (ESBL) determinants by PCR and sequencing. Then,
      16S rRNA methylase genes were detected among ESBL-producing isolates. Clonal
      relatedness of the E. coli isolates was examined by pulsed-field gel
      electrophoresis. Conjugation experiments were performed to investigate the
      association of 16S rRNA methylases and ESBLs, and plasmid contents were also
      characterized. Among 247 E. coli isolates, 74 (29.96%) isolates were positive for
      blaCTX-M genes, 42 from pets (12 from cats and 30 from dogs) and 32 from poultry
      (12 from chickens and 20 from ducks). The most common CTX-M type in isolates from
      pets was blaCTX-M-14, whereas blaCTX-M-27 was the most common for poultry. rmtB
      was dectected in 39 of the 74 blaCTX-M-positive isolates, 18 from pets and 21
      from poultry. One strain from a pet was found to harbor blaCTX-M-14, blaCTX-M-15,
      and rmtB. blaCTX-M and rmtB were found to be colocated on the same transferable
      plasmid in 16 isolates. These genes were on the same or similar plasmids (eight
      F2:A-:B- and two IncN) in isolates from ducks, whereas they were colocated on the
      similar F2:A-:B- or similar F33:A-:B- plasmids in isolates of pets origin. In
      conclusion, similar F2:A-:B- plasmids and similar F33:A-:B- plasmids are
      responsible for the dissemination of both rmtB and blaCTX-Mgenes in E. coli
      isolates from poultry and pets, respectively. 

PMID- 24290676
TI  - Impact of sulfur dioxide and temperature on culturability and viability of
      Brettanomyces bruxellensis in Wine.
AB  - Brettanomyces is a major threat to red wine quality, causing off-odors such as
      "medicinal," "barnyard," or even "sewage" during aging. Although sulfites (SO2)
      are used to limit spoilage by these yeast cells, reduced storage temperatures may
      lessen SO2 requirements. To test this hypothesis, a 4 | 4 factorial experimental
      design with molecular SO2(mSO2) concentration (0.0, 0.2, 0.5, or 1.1 mg/liter)
      and storage temperature (22, 18, 15, or 10 degrees C) was devised. Of three
      strains evaluated, B5 was the lone strain to regain culturability following
      exposure to 0.5 mg/liter mSO2 (18 degrees C), whereas only F3 remained culturable
      in the absence of mSO2 at 10 degrees C. Application of fluorescence microscopy
      using two different probes and quantitative PCR assays revealed only a 2-log
      reduction in metabolically active cells from wines with SO2 that were not
      culturable on nonselective media. Culturability in these wines eventually
      returned regardless of the concentration of mSO2 present. In addition, 4
      ethylphenol production ceased upon addition of SO2. These findings provide
      additional support that Brettanomyces can enter a "viable-but-not-culturable"
      state upon exposure to sulfites. Given the diversity among strains, maintaining
      conditions of <=15 degrees C and >=0.4 mg/liter mSO2 will help limit spoilage by
      Brettanomyces but will not lead to its complete eradication. 

PMID- 24290677
TI  - Increase of fumonisin b2 and ochratoxin a production by black Aspergillus species
      and oxidative stress in grape berries damaged by powdery mildew.
AB  - Powdery mildew (PM), caused by the fungus Erysiphe necator, is one of the most
      widespread fungal disease of grape and may cause extensive openings on the berry
      surface during the infection. We evaluated the effect of damage caused by PM in
      grape berries on the growth of and mycotoxin production by Aspergillus and on the
      oxidative stress in infected berries. Berries of Vitis vinifera L. cv. Negroamaro
      with sound skin (SS) and those naturally infected by PM were surface sterilized
      and inoculated with either fumonisin B2(FB2)-producing strains of Aspergillus
      niger or ochratoxin A (OTA)-producing strains of Aspergillus carbonarius and
      incubated at 20 and 30 degrees C. The PM berries were significantly more
      susceptible to both Aspergillus colonization (5 to 15 times more susceptible) and
      OTA and FB2 contamination (2 to 9 times more susceptible) than were SS berries.
      The highest toxin concentration was detected in inoculated PM berries both for
      OTA (9 ng/g) at 20 degrees C and for FB2 (687 ng/g) at 30 degrees C. In
      inoculated SS and PM berries, although malondialdehyde and hydrogen peroxide
      concentrations did not increase, the two black Aspergillus species caused a
      significant decrease in ascorbate content, thus inducing a pro-oxidant effect.
      These results indicate that grape berries affected by PM are more susceptible to
      black Aspergillus growth and to production and/or accumulation of FB2 and OTA.
      Thus, preventive control of E. necator on grape berries could reduce the
      mycotoxicological risk from black Aspergillus infection. 

PMID- 24290678
TI  - Assessment of the inhibition of ricin toxicity by lactose in milk.
AB  - The effect of lactose at the concentration typically found in milk (134 mM) on
      the ability of ricin to inhibit protein synthesis in HeLa cells was studied.
      Ricin (0.001 to 300 MUg/ml) that was either not treated or treated with 134 mM
      lactose was added to test tubes containing 1 ml of HeLa cells (approximately 3 *
      10(5) cells in a low-leucine medium). After 2 h of incubation at 37 degrees C,
      0.5 MUCi of L-[U-(14)C]-leucine was added to each tube and incubated for another
      60 min. The cells were harvested by centrifugation and lysed, and cellular
      proteins were separated. The amount of radioactivity incorporated into the
      proteins was determined by liquid scintillation. The biological activity of
      ricin, i. e., the amount of radioactivity in a sample relative to that of the
      control (cells not treated with ricin), was calculated for each treatment. The
      inhibitory effect of 134 mM lactose on the biological activity of ricin was only
      significant at concentrations of ricin below 1 MUg/ml. At higher ricin
      concentrations, the effect of 134 mM lactose decreased as the concentration of
      ricin increased, resulting in an increase in the inhibition of proteins
      synthesis. Our results also indicated that bovine milk, when used in place of 134
      mM lactose, was more effective for reducing the activity of ricin at
      concentrations below 1 MUg/ml but was ineffective against ricin concentrations
      greater than 1 MUg/ml. These results suggest that milk may not protect against
      ricin intoxication at the concentration (0.89 MUg/ml) equivalent to the lowest
      limit of its 50 % lethal dose for a 20-kg child consuming 225 ml (8 oz) of milk. 

PMID- 24290679
TI  - Prevalence of extended-spectrum b-lactamase-producing Salmonella on retail
      chicken in six provinces and two national cities in the People's Republic of
      China.
AB  - Prevalence of extended-spectrum beta-lactamase (ESBL)-producing Salmonella in
      food is not well documented. This study investigated the prevalence of ESBL
      producing Salmonella in 699 Salmonella isolates recovered from 1,152 retail
      chickens collected from six provinces and two national cities in the People's
      Republic of China in 2011. ESBL-producing isolates were screened by double-disk
      synergy test and confirmed using PCR and DNA sequencing. Of the 699 isolates
      tested, 60 (8.58%) were identified to be ESBL-producing Salmonella. Prevalence of
      ESBL-producing Salmonella was the highest in Shanghai city (17 [24.64%] of 69),
      followed by Shaanxi (10 [15.38%] of 65), Fujian (9 [11.69%] of 77), Guangdong (9
      [7.69%] of 117), Sichuan (5 [7.25%] of 69), Beijing (6 [5.17%] of 116), Henan (4
      [4.65%] of 86), and Guangxi (0 [0%] of 100) province. Significant difference (P <
      0.05) in the prevalence of ESBL-producing Salmonella was found among six
      provinces and two cities. No significant difference (P > 0.05) in the prevalence
      was found between wet markets and supermarkets or between whole chickens and
      chopped chickens. The prevalence of ESBL-producing Salmonella differed
      significantly (P < 0.05) among different seasons, being higher in autumn than in
      spring and winter. Overall, ESBL-producing Salmonella varied significantly (P <
      0.05) among 12 detected Salmonella serotypes: Abony (1 [33.33%] of 3), Indiana
      (28 [28.57%] of 98), Edinburg (6 [24.00%] of 25), Shubra (2 [20.00%] of 10),
      Uppsala (1 [16.67%] of 6), Thompson (8 [14.81%] of 54), Haardt (1 [12.50%] of 8),
      Agona (3 [9.68%] of 31), Gueuletapee (1 [6.25%] of 16), Typhimurium (4 [5.56%] of
      72), Heidelberg (1 [4.55%] of 22), and Enteritidis (4 [3.17%] of 126). This study
      revealed that ESBL-producing Salmonella do exist in retail chicken in the
      People's Republic of China and that the potential risk of their presence in foods
      needs further exploration. 

PMID- 24290680
TI  - Evaluation of antimicrobial resistance profiles of escherichia coli isolates of
      broiler chickens at slaughter in Alberta, Canada.
AB  - This study was conducted to investigate antimicrobial resistance profiles of
      Escherichia coli isolates from broiler chickens in Alberta, Canada. Cecal
      contents of broiler chickens from 24 flocks were collected at slaughter between
      January and March 2005 for culture and antimicrobial susceptibility testing
      against a panel of 15 antimicrobials using a broth microdilution technique. Of
      600 E. coli isolates tested, 475 (79.2%) were resistant to one or more
      antimicrobials, 326 (54.3%) were resistant to three or more antimicrobials, 65
      (10.8%) were resistant to five or more antimicrobials, and 15 (2.5%) were
      resistant to seven or more antimicrobials. The most common resistance was to
      tetracycline (69.2%), followed by streptomycin (48.2%), kanamycin (40.3%), and
      sulfisoxazole (38.0%). None of the E. coli isolates were resistant to amikacin,
      ceftriaxone, or ciprofloxacin. Of the isolates that were resistant to two or more
      antimicrobials, the most common multidrug resistance patterns were streptomycinte
      tracycline (44.0%), streptomycin-sulfisoxazole-tetracycline (30.7%), and
      kanamycin-streptomycin-sulfisoxazole-tetracycline (23.5%). Resistance to
      tetracycline and kanamycin (odds ratio = 46.7, P = 0.0001) was highly associated,
      followed by resistance to streptomycin and sulfisoxazole (odds ratio = 12.0, P =
      0.0001), and streptomycin and tetracycline (odds ratio = 10.3, P = 0.0001). The
      flock level prevalence of resistance varied from 16.7% for chloramphenicol to
      100.0% for ampicillin, streptomycin, sulfisoxazole, and tetracycline. The results
      of this study provided baseline information on antimicrobial susceptibility of E.
      coli isolates of broiler chickens at slaughter in Alberta, which can serve as a
      bench mark for future research. 

PMID- 24290681
TI  - Internalization of Escherichia coli O157:H7 following spraying of cut shoots when
      leafy greens are regrown for a second crop.
AB  - Both spinach and lettuce were grown to harvest, cut, and then regrown after
      spraying the cut shoots with irrigation water contaminated with Escherichia coli
      O157:H7. Plant tissue was collected on the day of spraying and again 2 and 14
      days later for analysis of total and internalized E. coli O157:H7 populations.
      Internalization of E. coli O157:H7 occurred on the day of spraying, and larger
      populations were internalized as the level in the spray increased. Tissue repair
      was slow and insufficient to prevent infiltration of E. coli O157:H7;
      internalized E. coli O157:H7 in shoots cut 5 days prior to exposure to E. coli
      O157:H7-contaminated water were not significantly different from levels in shoots
      cut on the same day of spraying with contaminated water (P > 0.05). Two days
      after spraying plants with a high level of E. coli O157:H7 (7.3 log CFU/ml),
      levels of internalized E. coli O157:H7 decreased by ca. 2.6 and 1.3 log CFU/g in
      Tyee and Bordeaux spinach, respectively, whereas populations of internalized E.
      coli O157:H7 decreased very little (ca. 0.4 log CFU/g) in lettuce plants that had
      been sprayed either on the same day as cutting or 1 day after cutting. When cut
      plants were sprayed with irrigation water at a lower contamination level (4.5 log
      CFU/ml), internalized E. coli O157:H7 was not detected in either spinach or
      lettuce plants 2 days later and therefore would not likely be of concern when the
      crop was harvested. 

PMID- 24290682
TI  - In vitro assessment of the susceptibility of planktonic and attached cells of
      foodborne pathogens to bacteriophage p22-mediated salmonella lysates.
AB  - This study was designed to evaluate the lytic activity of bacteriophage P22
      against Salmonella Typhimurium ATCC 19585 (Salmonella Typhimurium P22(-)) at
      various multiplicities of infections (MOIs), the susceptibility of preattached
      Salmonella cells against bacteriophage P22, and the effect of P22-mediated
      bacterial lysates (extracellular DNA) on the attachment ability of Listeria
      monocytogenes ATCC 7644 and enterohemorrhagic Escherichia coli ATCC 700927 to
      surfaces. The numbers of attached Salmonella Typhimurium P22(-) cells were
      effectively reduced to below the detection limit (1 log CFU/ml) at the fixed
      inoculum levels of 3 * 10(-) CFU/ml (MOI = 3.12) and 3 * 10(3) CFU/ml (MOI =
      4.12) by bacteriophage P22. The attached Salmonella Typhimurium P22(-) cells
      remained more than 2 log CFU/ml, with increasing inoculum levels from 3 * 10(4)
      to 3 * 10(7) CFU/ml infected with 4 * 10(8) PFU/ml of P22. The number of
      preattached Salmonella Typhimurium P22(-) cells was noticeably reduced by 2.72
      log in the presence of P22. The highest specific attachment ability values for
      Salmonella Typhimurium P22(-), Salmonella Typhimurium ATCC 23555 carrying P22
      prophage (Salmonella Typhimurium P22(+)), L. monocytogenes, and enterohemorrhagic
      E. coli were 2.09, 1.06, 1.86, and 1.08, respectively, in the bacteriophage
      mediated cell-free supernatants (CFS) containing high amounts of extracellular
      DNA. These results suggest that bacteriophages could potentially be used to
      effectively eliminate planktonic and preattached Salmonella Typhimurium P22(-)
      cells with increasing MOI. However, further research is needed to understand the
      role of bacteriophage-induced lysates in bacterial attachment, which can provide
      useful information for the therapeutic use of bacteriophage in the food system. 

PMID- 24290683
TI  - Molecular characterization and antibiotic susceptibility of Vibrio vulnificus in
      retail shrimps in Hangzhou, People's Republic of China.
AB  - Vibrio vulnificus is a gram-negative bacterium that occurs naturally in estuarine
      and marine water and is associated with wound infections or septicemia related to
      the consumption of raw shellfish in humans. The molecular characteristics and
      antibiotic susceptibilities of V. vulnificus strains in shrimps from retail
      markets in Hangzhou, People's Republic of China, were investigated in this study.
      Thirty-three samples were positive for V. vulnificus in 78 shrimp samples which
      were collected from 15 retail markets between July and August 2012; the most
      probable-number values ranged from 3 to 1,600 g(-1) in these positive samples,
      with a median most-probable-number value of 72 g(-1). Twenty-five biotype 1
      strains and eight biotype 2 strains were identified by biochemical tests, and all
      strains could be definitively genotyped. By 16S rRNA genotyping, 21.2% (7 of 33)
      were classified as genotype A, 63.6% (21 of 33) as genotype B, and 15.2% (5 of
      33) as genotype AB, while by virulence-correlated gene (vcg) typing, 21.2% (7 of
      33) were characterized as genotype E and 78.8% (26 of 33) were genotype C. More
      than 50% of those isolates were identified as the potentially virulent type vcg
      type C-16S rRNA B (CB). The antibiotic susceptibilities of the V. vulnificus
      strains to 21 antimicrobial agents were tested as well. Some strains showed
      resistance or intermediate resistance to cefepime (3.03%), tetracycline (6.06%),
      aztreonam (24.24%), streptomycin (45.45%), gentamicin (93.94%), tobramycin
      (100%), and cefazolin (100%). Multiple-locus variable-number tandem repeat-based
      fingerprinting analysis (MLVA) was successfully applied to these 33 isolates and
      yielded 30 patterns that clustered into two MLVA groups; with a calculated
      Simpson's index of diversity of 0.994, this revealed that MLVA had great
      discriminating power for V. vulnificus. To minimize the potential risk of V.
      vulnificus infections due to the consumption of raw shrimp, it is necessary to
      monitor the hygiene status of seafood. 

PMID- 24290684
TI  - Impact of sampling area and location on measurement of indicator organisms during
      beef carcass interventions.
AB  - The effect of the sponge sample collection site on the recovery of multiple
      indicator organisms from beef carcass surfaces was evaluated to simplify and
      validate our previous sampling method for ease of implementation as a general
      protocol. Sponge samples were collected at three beef processing plants using hot
      water or acidic antimicrobials as interventions. Two 4,000-cm(2) samples were
      collected from preevisceration carcasses (n = 248), one from the inside and
      outside round area (top site) and one from the navel-plate-brisket-foreshank area
      (bottom site). One-half of the samples (n = 124) were collected before a wash
      cabinet intervention and the other half after the intervention. The numbers of
      total aerobic bacteria, Enterobacteriaceae, coliforms, and Escherichia coli were
      determined for one-half of each individual sponge sample. The other halves of the
      sponges were combined to represent a top plus bottom 8,000-cm(2) SAMPLE: For the
      preintervention carcasses, 4,000-cm(2) samples collected from the top or bottom
      sites of the carcasses were not significantly different (P > 0.05) from each
      other or from the 8,000-cm(2) combined sample in recovery of the indicator
      organisms. Significant reductions of indicator organisms were observed in all
      three types of sponge samples after intervention; however, samples collected from
      the bottom site recovered less organisms (P < 0.05) compared with samples of the
      other types. These results suggested that samples collected from either the top
      or the bottom site of the carcasses with this method are suitable for monitoring
      indicator organisms as long as the same sampling site is consistently used. 

PMID- 24290685
TI  - Inhibition of Listeria monocytogenes by propionic acid-based ingredients in cured
      deli-style Turkey.
AB  - Listeria monocytogenes growth can be controlled on ready-to-eat meats through the
      incorporation of antimicrobial ingredients into the formulation or by
      postlethality kill steps. However, alternate approaches are needed to provide
      options that reduce sodium content but maintain protection against pathogen
      growth in meats after slicing. The objective of this study was to determine the
      inhibition of L. monocytogenes by propionic acid-based ingredients in high
      moisture, cured turkey stored at 4 or 7 degrees C. Six formulations of sliced,
      cured (120 ppm of NaNO2 ), deli-style turkey were tested, including control
      without antimicrobials, 3.2% lactate-diacetate blend (LD), 0.4% of a liquid
      propionate-benzoate-containing ingredient, or 0.3, 0.4, and 0.5% of a liquid
      propionate-containing ingredient. Products were inoculated with 5 log CFU L.
      monocytogenes per 100-g package (3 log CFU/ml rinsate), vacuum-sealed, and stored
      at 4 or 7 degrees C for up to 12 weeks; and populations were enumerated by
      plating on modified Oxford agar. As expected, the control without antimicrobials
      supported rapid growth, with >2 log average per ml rinsate increase within 4
      weeks of storage at 4 degrees C, whereas growth was observed at 6 weeks for the
      LD treatment. For both replicate trials, all treatments that contained liquid
      propionate or propionate-benzoate limited L. monocytogenes growth to an increase
      of <1 log through 9 weeks storage at 4 degrees C. Sporadic growth (>1-log
      increase) was observed in individual samples for all propionate-containing
      treatments at weeks 10, 11, and 12. As expected, L. monocytogenes grew more
      rapidly when products were stored at 7 degrees C, but trends in relative
      inhibition were similar to those observed at 4 degrees C. These results verify
      that propionate-based ingredients inhibit growth of L. monocytogenes on sliced,
      high-moisture, cured turkey and can be considered as an alternative to reduce
      sodium-based salts while maintaining food safety. 

PMID- 24290686
TI  - sigma(B) plays a limited role in the ability of Listeria monocytogenes strain
      F2365 to survive oxidative and acid stress and in its virulence characteristics.
AB  - Listeria monocytogenes strain F2365 was the first strain representative of
      serotype 4b (lineage I) to be sequenced in 2004, suggesting it could become the
      model organism for this serotype, which is associated with most human outbreaks
      of listeriosis worldwide to date. F2365 itself is an outbreak strain that was
      involved in the listeriosis outbreak associated with Mexican-style soft cheese in
      California in 1985. In this study, we show through phenotypic and transcriptomic
      analysis that L. monocytogenes strain F2365 has reduced ability to respond to
      acid and oxidative stress. F2365 has neither the sigma(B)-dependent ability to
      survive acid or oxidative stress nor the sigma(B)-dependent ability to infect
      Caco-2 epithelial cells in vitro or guinea pigs in vivo. More studies are needed
      to determine whether the atypical sigma(B)-independent response to stress
      observed in F2365 is strain specific, serotype specific, or even lineage
      specific. 

PMID- 24290687
TI  - Transfer of methicillin-resistant Staphylococcus aureus from retail pork products
      onto food contact surfaces and the potential for consumer exposure.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has
      developed resistance to beta-lactam antibiotics and has been isolated at low
      population numbers in retail meat products. The objectives of this study were to
      estimate the potential transfer of MRSA from contaminated retail pork products to
      food contact surfaces and to estimate the potential for human exposure to MRSA by
      contact with those contaminated surfaces. Pork loins, bacon, and fresh pork
      sausage were inoculated with a four-strain mixed MRSA culture over a range of
      populations from approximately 4 to 8 log, vacuum packaged, and stored for 2
      weeks at 5 degrees C to simulate normal packaging and distribution. Primary
      transfer was determined by placing inoculated products on knife blades, cutting
      boards, and a human skin model (pork skin) for 5 min. Secondary transfer was
      determined by placing an inoculated product on the contact surface, removing it,
      and then placing the secondary contact surface on the initial contact surface. A
      pork skin model was used to simulate transfer to human skin by placing it into
      contact with the contact surface. The percentages of transfer for primary
      transfer from the inoculated products to the cutting board ranged from 39 to 49%,
      while the percentages of transfer to the knife ranged from 17 to 42%. The
      percentages of transfer from the inoculated products to the pork skin ranged from
      26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all
      products and contact surfaces. Statistical analysis showed no significant
      differences in the amounts of transfer between transfer surfaces and across cell
      concentrations. 

PMID- 24290688
TI  - Staphylococcal poisoning foodborne outbreak: epidemiological investigation and
      strain genotyping.
AB  - In June 2011, an outbreak of Staphylococcus aureus enterotoxin food poisoning
      gastroenteritis occurred in Turin, Italy, following a catered dinner party at a
      private home. Within a few hours, 26 of the 47 guests experienced
      gastrointestinal illness, and 9 were hospitalized. A retrospective cohort study
      using a standardized questionnaire was carried out, and the risk ratios for each
      food item were calculated. The analysis indicated consumption of seafood salad as
      the most probable cause of the outbreak (risk ratio = 11.72; 95 % confidence
      interval, 1.75 to 78.54). Biological samples were collected from four of the
      hospitalized guests (stool and vomit), nasal mucosa swabs from three food
      handlers employed with the caterer, and available food residuals. All stool and
      vomit samples tested positive for enterotoxigenic S. aureus. As residues of the
      seafood salad were no longer available for sampling, suspected contamination
      could not be verified. However, no other food was found contaminated by S. aureus
      or its enterotoxins. All isolates from the biological samples were characterized
      at the genomic level by means of two multiplex PCR protocols to determine the
      presence of genes encoding staphylococcal enterotoxins, pulsed-field gel
      electrophoresis and staphylococcal protein A gene (spa) typing to describe their
      genetic profiles. All the isolates presented genes encoding SEA and SEI; the
      pulsed-field gel electrophoresis genetic profiles revealed the same pulsotype in
      the microorganism isolated from the hospitalized guests as in one of the isolates
      from a food handler's nasal mucosa, and the spa typing analysis reported two
      closely related spa types (t701 and t267), implicating the food handler as the
      most likely outbreak source. 

PMID- 24290689
TI  - Current intervention strategies for the microbial safety of sprouts.
AB  - Sprouts have gained popularity worldwide due to their nutritional values and
      health benefits. The fact that their consumption has been associated with
      numerous outbreaks of foodborne illness threatens the $250 million market that
      this industry has established in the United States. Therefore, sprout
      manufacturers have utilized the U.S. Food and Drug Administration recommended
      application of 20,000 ppm of calcium hypochlorite solution to seeds before
      germination as a preventative method. Concentrations of up to 200 ppm of chlorine
      wash are also commonly used on sprouts. However, chlorine-based treatment
      achieves on average only 1- to 3-log reductions in bacteria and is associated
      with negative health and environmental issues. The search for alternative
      strategies has been widespread, involving chemical, biological, physical, and
      hurdle processes that can achieve up to 7-log reductions in bacteria in some
      cases. The compilation here of the current scientific data related to these
      techniques is used to compare their efficacy for ensuring the microbial safety of
      sprouts and their practicality for commercial producers. Of specific importance
      for alternative seed and sprout treatments is maintaining the industry-accepted
      germination rate of 95% and the sensorial attributes of the final product. This
      review provides an evaluation of suggested decontamination technologies for seeds
      and sprouts before, during, and after germination and concludes that thermal
      inactivation of seeds and irradiation of sprouts are the most practical stand
      alone microbial safety interventions for sprout production. 

PMID- 24290690
TI  - Explaining the risk of foodborne illness associated with restaurants: the
      environmental health specialists network (EHS-Net).

PMID- 24290691
TI  - Handling practices of fresh leafy greens in restaurants: receiving and training.
AB  - Multiple foodborne illness outbreaks have been associated with the consumption of
      fresh produce. Investigations have indicated that microbial contamination
      throughout the farm-to-fork continuum often contributed to these outbreaks.
      Researchers have hypothesized that handling practices for leafy greens in
      restaurants may support contamination by and proliferation and amplification of
      pathogens that cause foodborne illness outbreaks. However, limited data are
      available on how workers handle leafy greens in restaurants. The purpose of this
      study was to collect descriptive data on handling practices of leafy greens in
      restaurants, including restaurant characteristics, types of leafy greens used,
      produce receipt, and food safety training and certification. As a federal
      collaborative partner with the Environmental Health Specialists Network (EHS-Net)
      of the Centers for Disease Control and Prevention, the U.S. Food and Drug
      Administration (FDA) recommended that EHS-Net participants survey handling
      practices for leafy greens in restaurants. The recommendations in the FDA's Guide
      to Minimize Microbial Food Safety Hazards of Leafy Greens are significant to this
      study for comparison of the results. The survey revealed that appropriate
      handling procedures assist in the mitigation of other unsafe handling practices
      for leafy greens. These results are significant because the FDA guidance for the
      safe handling of leafy greens was not available until 2009, after the survey had
      been completed. The information provided from this study can be used to promote
      additional efforts that will assist in developing interventions to prevent future
      foodborne illness outbreaks associated with leafy greens. 

PMID- 24290692
TI  - Ground beef handling and cooking practices in restaurants in eight States.
AB  - Eating in table-service restaurants has been implicated as a risk factor for
      Escherichia coli O157:H7 infection. To explore this association and learn about
      the prevalence of risky ground beef preparation practices in restaurants, the
      Environmental Health Specialists Network (EHS-Net) assessed ground beef handling
      policies and practices in restaurants in California, Colorado, Connecticut,
      Georgia, Minnesota, New York, Oregon, and Tennessee. Eligible restaurants
      prepared and served hamburgers. EHS-Net specialists interviewed a restaurant
      employee with authority over the kitchen (defined as the manager) using a
      standard questionnaire about food safety policies, hamburger preparation
      policies, and use of irradiated ground beef. Interviews were followed by
      observations of ground beef preparation. Data from 385 restaurants were analyzed:
      67% of the restaurants were independently owned and 33% were chain restaurants;
      75% of the restaurants were sit down, 19% were quick service or fast food, and 6%
      were cafeteria or buffet restaurants. Eighty-one percent of restaurants reported
      determining doneness of hamburgers by one or more subjective measures, and 49%
      reported that they never measure the final cook temperatures of hamburgers. At
      least two risky ground beef handling practices were observed in 53% of
      restaurants. Only 1% of restaurants reported purchasing irradiated ground beef,
      and 29% were unfamiliar with irradiated ground beef. Differences in risky ground
      beef handling policies and practices were noted for type of restaurant ownership
      (independently owned versus chain) and type of food service style (sit down
      versus quick service or fast food). This study revealed the pervasiveness of
      risky ground beef handling policies and practices in restaurants and the need for
      educational campaigns targeting food workers and managers. These results
      highlight the importance of continued efforts to reduce the prevalence of E. coli
      O157:H7 in ground beef. 

PMID- 24290693
TI  - Frequency of inadequate chicken cross-contamination prevention and cooking
      practices in restaurants.
AB  - This study was conducted by the Environmental Health Specialists Network (EHS
      Net) of the Centers for Disease Control and Prevention. The purpose was to
      examine restaurant chicken preparation and cooking practices and kitchen
      managers' food safety knowledge concerning chicken. EHS-Net members interviewed
      managers about chicken preparation practices in 448 restaurants. The study
      revealed that many restaurants were not following U.S. Food and Drug
      Administration Food Code guidance concerning cross-contamination prevention and
      proper cooking and that managers lacked basic food safety knowledge about
      chicken. Forty percent of managers said that they never, rarely, or only
      sometimes designated certain cutting boards for raw meat (including chicken). One
      third of managers said that they did not wash and rinse surfaces before
      sanitizing them. Over half of managers said that thermometers were not used to
      determine the final cook temperature of chicken. Only 43% of managers knew the
      temperature to which raw chicken needed to be cooked for it to be safe to eat.
      These findings indicate that restaurant chicken preparation and cooking practices
      and manager food safety knowledge need improvement. Findings from this study
      could be used by food safety programs and the restaurant industry to target
      training and intervention efforts to improve chicken preparation and cooking
      practices and knowledge concerning safe chicken preparation. 

PMID- 24290694
TI  - Food worker experiences with and beliefs about working while ill.
AB  - Transmission of foodborne pathogens from ill food workers to diners in
      restaurants is an important cause of foodborne illness outbreaks. The U.S. Food
      and Drug Administration recommends that food workers with vomiting or diarrhea
      (symptoms of foodborne illness) be excluded from work. To understand the
      experiences and characteristics of workers who work while ill, workplace
      interviews were conducted with 491 food workers from 391 randomly selected
      restaurants in nine states that participated in the Environmental Health
      Specialists Network of the Centers for Disease Control and Prevention. Almost 60%
      of workers recalled working while ill at some time. Twenty percent of workers
      said that they had worked while ill with vomiting or diarrhea for at least one
      shift in the previous year. Factors significantly related to workers having said
      that they had worked while ill with vomiting or diarrhea were worker sex, job
      responsibilities, years of work experience, concerns about leaving coworkers
      short staffed, and concerns about job loss. These findings suggest that the
      decision to work while ill with vomiting or diarrhea is complex and
      multifactorial. 

PMID- 24290695
TI  - A multinational, multi-institutional study comparing positive surgical margin
      rates among 22393 open, laparoscopic, and robot-assisted radical prostatectomy
      patients.
AB  - BACKGROUND: Positive surgical margins (PSMs) are a known risk factor for
      biochemical recurrence in patients with prostate cancer (PCa) and are potentially
      affected by surgical technique and volume. OBJECTIVE: To investigate whether
      radical prostatectomy (RP) modality and volume affect PSM rates. DESIGN, SETTING,
      AND PARTICIPANTS: Fourteen institutions in Europe, the United States, and
      Australia were invited to participate in this study, all of which retrospectively
      provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP
      patients operated on between January 2000 and October 2011. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSES: The outcome measure was PSM rate. Multivariable
      logistic regression analyses and propensity score methods identified odds ratios
      for risk of a PSM for one modality compared with another, after adjustment for
      age, preoperative prostate-specific antigen, postoperative Gleason score,
      pathologic stage, and year of surgery. Classic adjustment using standard
      covariates was also implemented to compare PSM rates based on center volume for
      each minimally invasive surgical cohort. RESULTS AND LIMITATIONS: Open RP
      patients had higher-risk PCa at time of surgery on average and were operated on
      earlier in the study time period on average, compared with minimally invasive
      cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for
      laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences
      persisted, although were ameliorated, after statistical adjustments. Lower-volume
      centers had increased risks of PSM compared with the highest-volume center for
      both laparoscopic RP and robotic RP. The study is limited by its nonrandomized
      nature; missing data across covariates, especially year of surgery in many of the
      open cohort cases; lack of standardized histologic processing and central
      pathology review; and lack of information regarding potential confounders such as
      patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and
      individual surgeon caseload. CONCLUSIONS: This multinational, multi-institutional
      study of 22 393 patients after RP suggests that PSM rates might be lower after
      minimally invasive techniques than after open RP and that PSM rates are affected
      by center volume in laparoscopic and robotic cases. PATIENT SUMMARY: In this
      study, we compared the effectiveness of different types of surgery for prostate
      cancer by looking at the rates of cancer cells left at the margins of what was
      removed in the operations. We compared open, keyhole, and robotic surgery from
      many centers across the globe and found that robotic and keyhole operations
      appeared to have lower margin rates than open surgeries. How many cases a center
      and surgeon do seems to affect this rate for both robotic and keyhole procedures.

PMID- 24290696
TI  - Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery.
AB  - Hypoxia is a condition found in various intractable diseases. Here, we report
      self-assembled nanoparticles which can selectively release the hydrophobic agents
      under hypoxic conditions. For the preparation of hypoxia-responsive nanoparticles
      (HR-NPs), a hydrophobically modified 2-nitroimidazole derivative was conjugated
      to the backbone of the carboxymethyl dextran (CM-Dex). Doxorubicin (DOX), a model
      drug, was effectively encapsulated into the HR-NPs. The HR-NPs released DOX in a
      sustained manner under the normoxic condition (physiological condition), whereas
      the drug release rate remarkably increased under the hypoxic condition. From in
      vitro cytotoxicity tests, it was found the DOX-loaded HR-NPs showed higher
      toxicity to hypoxic cells than to normoxic cells. Microscopic observation showed
      that the HR-NPs could effectively deliver DOX into SCC7 cells under hypoxic
      conditions. In vivo biodistribution study demonstrated that HR-NPs were
      selectively accumulated at the hypoxic tumor tissues. As consequence, drug-loaded
      HR-NPs exhibited high anti-tumor activity in vivo. Overall, the HR-NPs might have
      a potential as nanocarriers for drug delivery to treat hypoxia-associated
      diseases.

PMID- 24290697
TI  - Manipulating the surface coating of ultra-small Gd2O3 nanoparticles for improved
      T1-weighted MR imaging.
AB  - In this report, monodispersed ultra-small Gd2O3 nanoparticles capped with
      hydrophobic oleic acid (OA) were synthesized with average particle size of 2.9
      nm. Two methods were introduced to modify the surface coating to hydrophilic for
      bio-applications. With a hydrophilic coating, the polyvinyl pyrrolidone (PVP)
      coated Gd2O3 nanoparticles (Gd2O3-PVP) showed a reduced longitudinal T1
      relaxation time compared with OA and cetyltrimethylammonium bromide (CTAB) co
      coated Gd2O3 (Gd2O3-OA-CTAB) in the relaxation study. The Gd2O3-PVP was thus
      chosen for its further application study in MRI with an improved longitudinal
      relaxivity r1 of 12.1 mM(-1) s(-1) at 7 T, which is around 3 times as that of
      commercial contrast agent Magnevist((r)). In vitro cell viability in HK-2 cell
      indicated negligible cytotoxicity of Gd2O3-PVP within preclinical dosage. In vivo
      MR imaging study of Gd2O3-PVP nanoparticles demonstrated considerable signal
      enhancement in the liver and kidney with a long blood circulation time. Notably,
      the OA capping agent was replaced by PVP through ligand exchange on the Gd2O3
      nanoparticle surface. The hydrophilic PVP grants the Gd2O3 nanoparticles with a
      polar surface for bio-application, and the obtained Gd2O3-PVP could be used as an
      in vivo indicator of reticuloendothelial activity.

PMID- 24290698
TI  - Promoter and lineage independent anti-silencing activity of the A2 ubiquitous
      chromatin opening element for optimized human pluripotent stem cell-based gene
      therapy.
AB  - Epigenetic silencing of retroviral transgene expression in pluripotent stem cells
      (PSC) and their differentiated progeny constitutes a major roadblock for PSC
      based gene therapy. As ubiquitous chromatin opening elements (UCOEs) have been
      successfully employed to stabilize transgene expression in murine hematopoietic
      and pluripotent stem cells as well as their differentiated progeny, we here
      investigated UCOE activity in their human counterparts to establish a basis for
      future clinical application of the element. To this end, we demonstrate profound
      anti-silencing activity of the A2UCOE in several human iPS and ES cell lines
      including their progeny obtained upon directed cardiac or hematopoietic
      differentiation. We also provide evidence for A2UCOE activity in murine iPSC
      derived hepatocyte-like cells, thus establishing efficacy of the element in cells
      of different germ layers. Finally, we investigated combinations of the A2UCOE
      with viral promoter/enhancer elements again demonstrating profound stabilization
      of transgene expression. In all these settings the effect of the A2UCOE was
      associated with strongly reduced promoter DNA-methylation. Thus, our data clearly
      support the concept of the A2UCOE as a generalized strategy to prevent epigenetic
      silencing in PSC and their differentiated progeny and strongly favors its
      application to stabilize transgene expression in PSC-based cell and gene therapy
      approaches. 

PMID- 24290699
TI  - Peptide encapsulation regulated by the geometry of carbon nanotubes.
AB  - In this work the encapsulation of an alpha-helical peptide in single carbon
      nanotubes (CNTs) with similar diameter and length but different geometry
      (armchair and zigzag) was investigated through molecular dynamics simulations and
      free energy calculations. Our simulation results showed that in vacuo it makes no
      evident difference whether the investigated peptide is encapsulated in armchair
      or zigzag CNTs; however, in aqueous solution the armchair CNT encapsulates the
      peptide remarkably easier than the zigzag CNT does. A detailed analysis revealed
      that the equilibrium conformation of the water molecules inside the CNTs with
      varying geometry mediates the peptide encapsulation. It suggests that the water
      molecules play an important role in regulating behaviors of biomolecules in bio
      systems. Then the impact of the CNT geometry on the conformational changes of the
      confined peptide was studied. Analyses of secondary structures showed the alpha
      helix of the peptide could be better maintained in the zigzag CNT. 

PMID- 24290700
TI  - Genetically encoded FRET-based biosensor for imaging MMP-9 activity.
AB  - A genetically encoded Forster Resonance Energy Transfer (FRET)-based biosensor
      that continuously monitors matrix metalloproteinase 9 (MMP-9) activity was
      developed. MMP-9 is an extracellularly acting endopeptidase with a prominent role
      in development, learning and memory, cancer metastasis, and stroke. To assess the
      biological function of the protease, determining the precise kinetics and
      localization of MMP-9 activity is required. The nontoxic, genetically encoded
      FRET biosensor presented herein is anchored in the cellular membrane and thus
      provides an important advantage over currently employed probes. The biosensor
      allows the study of the proteolytic activity of MMP-9 with high temporal and
      subcellular resolution at the precise region of MMP-9 action on the cell. The
      applicability of the biosensor both in vitro and in living cells was demonstrated
      by ratiometrically analyzing the cleavage of the biosensor by a purified auto
      activating mutant of MMP-9 and endogenously secreted protease in cultured tumor
      and neuronal cells. The precise kinetics of endogenous MMP-9 activity was
      measured, which demonstrates in a straight-forward manner the applicability of
      the biosensor concept. 

PMID- 24290701
TI  - Interest of telemicrosurgery in peripheral nerve tumors: about a series of seven
      cases.
AB  - Surgery of the chronic peripheral nerve lesion should not only limit recurrence
      after excision, but it should also limit the sensory and motor sequelae. The aim
      of this work was to study the interest of telemicrosurgery to improve this
      result. Our series included 7 patients with peripheral nerve neuroma and tumors
      including two cases of hereditary neurofibromatosis. A Da Vinci S((r)) robot
      equipped with microsurgical instruments was used for intraneural dissection. One
      case was performed with minimally invasive approach. At last follow-up, the pain
      decreased from 6/10 preoperatively to 3/10 postoperatively. The sensory deficit
      was stable except for two patients, whose sensory function was improved. No
      recurrence was noted. Telemicrosurgery seems to have two interests in the
      treatment of chronic peripheral nerve lesions: it reduces the size of incisions
      and increases the accuracy of surgery. These preliminary results suggest that
      surgical robots could play an essential role in microsurgery. 

PMID- 24290702
TI  - Absence of micronucleus formation in CHO-K1 cells cultivated in platelet lysate
      enriched medium.
AB  - Human platelet lysate (PL) represents an effective substitute of fetal bovine
      serum (FBS) for mesenchymal stromal cell (MSC) cultivation. Compared to FBS, PL
      favors MSC proliferation significantly shortening the population doubling time
      and avoiding the risks related to the use of animal derivatives. Growth factors
      contained in the platelets are released upon platelet disruption following
      freezing/thawing cycles or as we have recently described by using ultrasound. We
      have investigated whether the increased cell proliferation achieved by using PL
      could induce mitotic stress and whether the potential formation of free radicals
      during PL production by ultrasound could cause chromosomal instability in
      mammalian cells. We have applied an image analysis assisted high content
      screening (HCS) in vitro micronucleus assay in the Chinese Hamster Ovarian K1
      (CHO-K1) rodent mammalian cell line. PL was produced by sonication; for the
      micronucleus assay, CHO-K1 cells were exposed to increasing concentrations of PL.
      Cytokinesis was blocked by cytochalasin B, nuclei were stained with bisbenzimide
      and images were acquired and analyzed automatically using an HCS system, both
      with a 20* and a 10* objective. Our results suggest that growth stimulus induced
      by the use of PL did not significantly increase micronucleus formation in CHO-K1
      cells compared to negative control. Micronucleus testing in conjunction with HCS
      could represent a valid tool to evaluate the safety of ancillary materials used
      in the production of cell-based medicinal products. 

PMID- 24290704
TI  - Aggressive infective endocarditis and the importance of early repeat
      echocardiographic imaging.

PMID- 24290703
TI  - Modified in vivo lung perfusion allows for prolonged perfusion without acute lung
      injury.
AB  - OBJECTIVES: In vivo lung perfusion (IVLP) is an emergent strategy to treat lung
      metastases because it allows localized delivery of chemotherapy with minimal
      systemic exposure. Previously, short-term (+/- 30 minutes) IVLP resulted in
      variable efficacy and significant lung toxicity. We hypothesize that a modified
      IVLP strategy derived from an ex vivo lung perfusion technique could minimize
      lung injury. Our objective was to demonstrate the feasibility and safety of a
      modified prolonged (4 hours) IVLP. METHODS: Six Yorkshire pigs were used for the
      experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary
      veins were cannulated, and the left lung was isolated in situ. IVLP was performed
      at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Goteburg,
      Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left
      atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated
      and supplied with CO2 to physiologic levels before entering the lungs. A
      protective mode of ventilation was used. After IVLP, the left lung was allowed to
      reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary
      vascular resistance were used to assess left lung physiology. Histologic signs of
      lung injury were assessed before and after IVLP, and 4 hours after reperfusion.
      RESULTS: Lung function parameters were stable throughout the 4-hour IVLP and
      during reperfusion. No significant histologic evidence of acute lung injury was
      observed. CONCLUSIONS: Four hours of IVLP is feasible without adding significant
      lung injury. Prolonged perfusion time and a protective protocol might provide
      safer and more efficacious treatment of pulmonary metastases.

PMID- 24290705
TI  - First human totally endoscopic aortic valve replacement: an early report.

PMID- 24290707
TI  - Early and midterm outcomes of hemiarch replacement combined with stented elephant
      trunk in the management of acute DeBakey type I aortic dissection: comparison
      with total arch replacement.
AB  - OBJECTIVE: For patients with acute DeBakey type I aortic dissection without an
      intimal tear in the arch, the early and midterm outcomes of hemiarch replacement
      with stented elephant trunk were compared with those of total arch replacement.
      METHODS: From January 2006 to December 2011, 197 patients with acute type I
      aortic dissection were identified without an intimal tear in the arch. Of the 197
      patients, 71 underwent hemiarch replacement with stented elephant trunk
      implantation (hemiarch group) and 84 underwent ascending aorta and total arch
      replacement with stented elephant trunk implantation (total arch group). RESULTS:
      The incidence of postoperative transient neurologic dysfunction, low cardiac
      output syndrome, and prolonged ventilation was lower in the hemiarch group (P<.05
      for all). The hospital mortality was 4.2% and 5.9% for the hemiarch and total
      arch groups, respectively (P=.91). No difference was detected in survival between
      the 2 groups (P=.56). Complete thrombosis in the false lumen of the residual arch
      was found in 92.1% of those undergoing hemiarch replacement. The rate of complete
      thrombosis in the false lumen of the distal aorta was similar between the 2
      groups (P>.05). The risk of an aortic event was similar for both groups (P=.62).
      CONCLUSIONS: For patients with acute DeBakey type I dissection without an intimal
      tear in the arch, hemiarch replacement with stented elephant trunk implantation
      was easily performed, with satisfactory early and midterm outcomes. For these
      selective patients, total arch replacement with the stented elephant trunk
      technique did not improve the late surgical results further.

PMID- 24290708
TI  - Functioning Cooley-Cutter aortic valve prosthesis 40 years after implantation.

PMID- 24290709
TI  - Surgical techniques for early-stage thymoma: video-assisted thoracoscopic
      thymectomy versus transsternal thymectomy.
AB  - OBJECTIVE: The present study compared the outcomes between patients who had
      undergone video-assisted thoracoscopic surgery (VATS) thymectomy and transsternal
      (TS) thymectomy for Masaoka stage I and II thymoma. METHODS: The outcomes of 262
      patients without myasthenia gravis who had undergone surgery for Masaoka stage I
      and II thymoma from January 2008 to December 2012 at our center were
      retrospectively evaluated. The study included 125 patients who had undergone
      unilateral VATS thymectomy (VATS group) and 137 patients who had undergone TS
      thymectomy (TS group). RESULTS: The VATS group had a shorter operative time than
      the TS group (170 vs 210 minutes, P < .001). The VATS group also had a smaller
      intraoperative blood loss (200 vs 450 mL, P < .001), smaller pleural drainage
      volume in the first 24 hours postoperatively (300 vs 500 mL, P < .0010), shorter
      postoperative pleural drainage duration (3 vs 5 days, P < .001), and shorter
      postoperative hospital stay (8 vs 10 days, P < .001). Four patients in the VATS
      group underwent conversion to open surgery because of injury to the innominate
      vein. The postoperative complication rate was similar between the 2 groups. One
      patient in the VATS group developed pleural recurrence, and one in the TS group
      developed local recurrence. CONCLUSIONS: Unilateral VATS thymectomy for Masaoka
      stage I and II thymoma is technically feasible and safe and is less invasive than
      TS thymectomy, with a shorter duration of surgery, less intraoperative blood
      loss, less postoperative pleural drainage, shorter postoperative pleural drainage
      duration, and shorter postoperative hospital stay. We have concluded that it is
      preferable to perform VATS thymectomy, although perhaps under certain
      circumstances sternotomy might be preferred. The oncologic outcomes were
      comparable between the 2 procedures. Additional follow-up is required to evaluate
      the long-term outcomes.

PMID- 24290710
TI  - Awake uniportal video-assisted thoracoscopic metastasectomy after a
      nasopharyngeal carcinoma.

PMID- 24290711
TI  - Venoarterial extracorporeal membrane oxygenation for right heart failure
      complicating left ventricular assist device use.

PMID- 24290713
TI  - Maintaining situational awareness in a cardiac intensive care unit.

PMID- 24290712
TI  - Myocardial damage influences short- and mid-term survival after valve surgery: a
      prospective multicenter study.
AB  - OBJECTIVE: Myocardial damage occurs after valve surgery, but its prognostic
      implication has not been evaluated. The aim of the present study was to assess
      the influence of myocardial damage on mortality and morbidity in patients
      undergoing aortic surgery (AVS) and mitral valve surgery (MVS). METHODS: In a
      prospective multicenter study from the cardiac surgery registry of the Puglia
      region, cardiac troponin I (cTnI) was measured immediately after and the morning
      after the intervention in consecutive patients undergoing AVS or MVS. The
      percentile ranks of the cTnI peak values within each center were analyzed.
      RESULTS: Of 965 patients (age, 67+/-12 years; 45.5% women), 579 had undergone AVS
      and 386 MVS. cTnI release was significantly greater in the MVS group than in the
      AVS group and in the nonsurvivors than in the survivors in both groups. The cTnI
      cutoff with the greatest sensitivity and specificity (60th percentile for AVS and
      91st for MVS) in predicting hospital mortality (2.6%) was also associated with a
      greater rate of postoperative complications and mortality within 3 months
      postoperatively (multivariate hazard ratio, 3.38; P=.005). Compared with the
      reference model, which included the multivariate predictors of hospital mortality
      (active endocarditis, New York Heart Association class III-IV, left ventricular
      ejection fraction<=30%, and cardiopulmonary bypass duration), the addition of
      cTnI greater than the cutoffs showed significant improvement in model performance
      (likelihood ratio test, P=.009; net reclassification improvement, 0.751; P<.001;
      integrated discrimination improvement, 0.048; P=.002; c-index 0.832 vs 0.838).
      CONCLUSIONS: An elevated postoperative cTnI level was an independent risk factor
      for mortality and morbidity. Measurement of the cTnI level improved the risk
      reclassification of patients undergoing AVS or MVS.

PMID- 24290714
TI  - Use of an automatic internal defibrillator to induce and maintain ventricular
      fibrillation during left ventricular assist device pump exchange.

PMID- 24290715
TI  - Minimizing chest wall trauma in single-port video-assisted thoracic surgery.

PMID- 24290716
TI  - The use of the Berlin Heart EXCOR in patients with functional single ventricle.
AB  - INTRODUCTION: The frequency and successful use of pediatric ventricular assist
      devices (VADs) as a bridge to cardiac transplantation have been steadily
      increasing since 2003, but the experience in patients with complex congenital
      heart disease has not been well described. Using a large prospectively collected
      dataset of children supported with the Berlin Heart EXCOR VAD, we have reviewed
      the experience in children with single ventricular anatomy or physiology (SV),
      and compared the results with those supported with biventricular circulation (BV)
      over the same time period. METHODS: The EXCOR Investigational Device Exemption
      study database was retrospectively reviewed. VAD implants under the primary
      cohort and compassionate use cohort between May 2007 and December 2011 were
      included in this review. RESULTS: Twenty-six of 281 patients supported with a VAD
      were SV. The most common diagnosis was hypoplastic left heart syndrome (15 of
      26). Nine patients were supported after neonatal palliative surgery (Blalock
      Taussig shunt or Sano), 12 after a superior cavopulmonary connection (SCPC), and
      5 after total cavopulmonary connection (TCPC). Two patients received
      biventricular assist devices, 1 after stage I surgery and 1 after stage II. SV
      patients were supported for a median time of 10.5 days (range, 1-363 days) versus
      39 days (range, 0-435 days) for BV (P = .01). The ability to be bridged to
      transplant or recovery in SV patients is lower than for BV patients (11 of 26
      [42.3%] vs 185 of 255 [72.5%]; P = .001). Three of 5 patients with TCPC were
      successfully bridged to transplant and were supported with 1 VAD. Seven of 12
      patients with SCPC were bridged to transplant, and only 1 of 9 patients supported
      after a stage I procedure survived. CONCLUSIONS: The EXCOR Pediatric VAD can
      provide a bridge to transplant for children with SV anatomy or physiology, albeit
      less successfully than in children with BV. In this small series, results are
      better in patients with SCPC and TCPC. VAD support for patients with shunted
      sources of pulmonary blood flow should be applied with caution.

PMID- 24290718
TI  - Cardiac hemangioma at the apex of the right ventricle: a case report and
      literature review.

PMID- 24290719
TI  - A benchmark test of accuracy and precision in estimating dynamical systems
      characteristics from a time series.
AB  - Characteristics of dynamical systems are often estimated to describe
      physiological processes. For instance, Lyapunov exponents have been determined to
      assess the stability of the cardio-vascular system, respiration, and, more
      recently, human gait and posture. However, the systematic evaluation of the
      accuracy and precision of these estimates is problematic because the proper
      values of the characteristics are typically unknown. We fill this void with a set
      of standardized time series with well-defined dynamical characteristics that
      serve as a benchmark. Estimates ought to match these characteristics, at least to
      good approximation. We outline a procedure to employ this generic benchmark test
      and illustrate its capacity by examining methods for estimating the maximum
      Lyapunov exponent. In particular, we discuss algorithms by Wolf and co-workers
      and by Rosenstein and co-workers and evaluate their performances as a function of
      signal length and signal-to-noise ratio. In all scenarios, the precision of
      Rosenstein's algorithm was found to be equal to or greater than Wolf's algorithm.
      The latter, however, appeared more accurate if reasonably large signal lengths
      are available and noise levels are sufficiently low. Due to its modularity, the
      presented benchmark test can be used to evaluate and tune any estimation method
      to perform optimally for arbitrary experimental data. 

PMID- 24290721
TI  - Effects of bilateral medial knee osteoarthritis on intra- and inter-limb
      contributions to body support during gait.
AB  - Patients with knee OA show altered gait patterns, affecting their quality of
      living. The current study aimed to quantify the effects of bilateral knee OA on
      the intra-limb and inter-limb sharing of the support of the body during gait.
      Fifteen patients with mild, 15 with severe bilateral knee OA, and 15 healthy
      controls walked along a walkway while the kinematic and kinetic data were
      measured. Compared with the controls, the patients significantly reduced their
      knee extensor moments and the corresponding contributions to the total support
      moment in the sagittal plane (p<0.05). For compensation, the mild OA group
      significantly increased the hip extensor moments (p<0.05) to maintain close-to
      normal support and a more symmetrical inter-limb load-sharing during double-limb
      support. The severe OA group involved compensatory actions of both the ankle and
      hip, but did not succeed in maintaining a normal sagittal total support moment
      during late stance, nor a symmetrical inter-limb load-sharing during double-limb
      support. In the frontal plane, the knee abductor moments and the corresponding
      contributions to the total support moment were not affected by the changes in the
      other joints, regardless of the severity of the disease. The observed
      compensatory changes suggest that strengthening of weak hip muscles is essential
      for body support during gait in patients with knee OA, but that training of weak
      ankle muscles may also be needed for patients with severe knee OA. 

PMID- 24290720
TI  - Analysis of the musculoskeletal loading of the thumb during pipetting--a pilot
      study.
AB  - Previous epidemiological studies indicate that the use of thumb-push mechanical
      pipettes is associated with musculoskeletal disorders (MSDs) in the hand. The
      goal of the current study was to analyze the loading in the muscle-tendon units
      in the thumb during pipetting. The hand is modeled as a multi-body linkage system
      and includes four fingers (index, long, ring, and little finger), a thumb, and a
      palm segment. Since the current study is focused on the thumb, the model includes
      only nine muscles attached to the thumb via tendons. The time-histories of joint
      angles and push force at the pipette plunger during pipetting were determined
      experimentally and used as model input; whereas forces in the muscle-tendon units
      in the thumb were calculated via an inverse dynamic approach combined with an
      optimization procedure. Results indicate that all nine muscles have force outputs
      during pipetting, and the maximal force was in the abductor pollicis brevis
      (APB). The ratio of the mean peak muscle force to the mean peak push force during
      the dispensing cycle was approximately 2.3, which is comparable to values
      observed in grasping tasks in the literature. The analysis method and results in
      the current study provide a mechanistic understanding of MSD risk factors
      associated with pipetting, and may be useful in guiding ergonomic designs for
      manual pipettes. 

PMID- 24290722
TI  - [A preliminary experience in the laparoscopic approach to bowel obstruction].
AB  - BACKGROUND: The laparoscopic approach to bowel obstruction is still
      controversial. OBJECTIVE: To evaluate our initial results in the laparoscopic
      treatment of bowel obstruction. MATERIAL AND METHODS: A retrospective study on
      patients diagnosed with bowel obstruction that underwent laparoscopic surgery
      within the time frame of January 2008 to June 30, 2012. The variables employed
      were: age, sex, occlusion etiology, previous surgeries, clinical progression,
      pneumoperitoneum creation, use of an auxiliary incision, anesthesia duration,
      conversion rate, postoperative hospital stay, time needed to tolerate liquids,
      and complications. RESULTS: Twenty-six patients, 18 women (69.2%) and 8 men
      (30.8%), with a mean age of 64.35 years (range: 21-92 years) were analyzed. The
      most frequent obstruction etiology was secondary to adhesions and presented in 12
      cases. Nine patients (34.6%) underwent a completely laparoscopic approach and
      laparoscopy was complemented by an auxiliary incision in another 9 patients
      (34.6%), resulting in 18 cases (69.2%) of successful laparoscopic approach. Eight
      patients (30.8%) required conversion to open surgery. The mean anesthesia
      duration was 95min (range: 55-165min), mean postoperative hospital stay was 6
      days (range: 3-72 days), and the mean amount of time needed to tolerate liquids
      was 3 days (range: 1-10 days). The patients that underwent complete laparoscopic
      approach presented with shorter hospital stay, they were able to ingest liquids
      earlier, and they presented with a lower number of postoperative complications;
      this latter variable was the only one that was statistically significant.
      CONCLUSIONS: The initial results of our experience were good, although more
      patients are needed in order to standardize and extend the use of this technique.

PMID- 24290723
TI  - [Capsule endoscope aspiration: a common complication?].

PMID- 24290724
TI  - [The Mexican consensus on gastroesophageal reflux disease. Part II].
AB  - OBJECTIVE: To update the themes of endoscopic and surgical treatment of
      Gastroesophageal Reflux Disease (GERD) from the Mexican Consensus published in
      2002. METHODS: Part I of the 2011 Consensus dealt with the general concepts,
      diagnosis, and medical treatment of this disease. Part II covers the topics of
      the endoscopic and surgical treatment of GERD. In this second part, an expert in
      endoscopy and an expert in GERD surgery, along with the three general
      coordinators of the consensus, carried out an extensive bibliographic review
      using the Embase, Cochrane, and Medline databases. Statements referring to the
      main aspects of endoscopic and surgical treatment of this disease were elaborated
      and submitted to specialists for their consideration and vote, utilizing the
      modified Delphi method. The statements were accepted into the consensus if the
      level of agreement was 67% or higher. RESULTS: Twenty-five statements
      corresponding to the endoscopic and surgical treatment of GERD resulted from the
      voting process, and they are presented herein as Part II of the consensus. The
      majority of the statements had an average level of agreement approaching 90%.
      CONCLUSION: Currently, endoscopic treatment of GERD should not be regarded as an
      option, given that the clinical results at 3 and 5 years have not demonstrated
      durability or sustained symptom remission. The surgical indications for GERD are
      well established; only those patients meeting the full criteria should be
      candidates and their surgery should be performed by experts.

PMID- 24290725
TI  - [Endoscopic diagnosis of an intramural hematoma presenting as an anticoagulant
      ileus].

PMID- 24290726
TI  - [Idiopathic sclerosing mesenteritis in the pediatric patient: a case report].

PMID- 24290727
TI  - The emergence of community-onset Clostridium difficile infection in a tertiary
      hospital in Singapore: a cause for concern.
AB  - Increasing rates of Clostridium difficile infection (CDI) among those without
      traditional risk factors have been reported mainly in Europe and North America.
      Here we describe the epidemiology, clinical features and ribotypes of CDI at
      National University Hospital (NUH), a 1000-bed tertiary care hospital in
      Singapore, from December 2011 to May 2012. All laboratory-confirmed CDI cases
      >=21 years old who gave informed consent were included. Clinical data were
      collected prospectively and participants underwent an interviewer-administered
      questionnaire. Cases were classified by healthcare facility exposure and severity
      according to the SHEA guidelines. Included cases were also subjected to PCR and
      were classified by ribotype. In total, 66 patients participated in the study, of
      which 33 (50.0%) were healthcare-facility-associated hospital onset (HCFA-HO). Of
      the 33 community-onset (CO) cases, 14 (42.4%) were HCFA-CO, 10 (30.3%) were
      indeterminate and 9 (27.3%) were community-associated (CA). Of the CA cases, a
      majority (90.9%) had prior exposure to a healthcare facility within the last 12
      weeks. Clinical characteristics, exposures and outcomes were not different
      between HO-CDI and CO-CDI. Diagnosis was delayed in CO-CDI compared with HO-CDI
      (4 days vs. 1 day; P=0.014). There was no difference in distribution of ribotypes
      between CO-CDI and HO-CDI, with 053 being most prevalent in both groups. CO-CDI
      increasingly contributes to the burden of CDI in NUH. This may reflect a trend in
      other parts of Asia. Healthcare professionals should be aware of the possible
      role of outpatient healthcare environments to CDI risk and thus extend control
      measures to outpatient settings.

PMID- 24290729
TI  - Influence of environmental factors on infrared eye temperature measurements in
      cattle.
AB  - Environmental factors were evaluated to determine potential limitations in using
      cattle eye temperatures obtained through infrared thermography (IRT) for early
      disease detection systems or in animal welfare research studies. The effects of
      the following factors on IRT eye temperatures in cattle and a fabricated
      surrogate "eye" were evaluated: camera to object distance, wind speed, camera
      settings (distance, emissivity, and humidity), and solar loading. Wind speed in
      both live animals and using a surrogate "eye" was found to decrease the IRT
      temperature. In the presence of ~ 7 km/h wind, the mean IRT eye temperature
      decreased by 0.43 +/- 0.13  degrees C and; at higher wind speeds (~ 12 km/h), the
      temperature decreased by 0.78 +/- 0.33  degrees C. Direct sunlight was found to
      increase the IRT eye temperature by 0.56 +/- 0.36  degrees C. It was determined
      that environmental factors impact IRT temperature measurements significantly and
      therefore must be managed to ensure reproducible and accurate readings.

PMID- 24290728
TI  - WWC1 genotype modulates age-related decline in episodic memory function across
      the adult life span.
AB  - BACKGROUND: Episodic memory (EM) declines with age and the rate of decline is
      variable across individuals. A single nucleotide polymorphism (rs17070145) in the
      WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and
      memory consolidation has previously been associated with EM performance, as well
      as differences in hippocampal engagement during EM tasks using functional
      magnetic resonance imaging (fMRI). In the current study, we explore the effect of
      this polymorphism on EM-related activity and cognitive performance across the
      adult life span using fMRI. METHODS: Two hundred thirty-two healthy, Caucasian
      subjects (18-89 years) completed a battery of cognitive tests, as well as an EM
      task during an fMRI scan. RESULTS: WWC1 T carriers had significantly better
      delayed recall performance than CC individuals (p = .006). The relationship
      between increasing age and recall scores (immediate and delayed) was also
      significantly different between WWC1 genotype groups (p = .01). In addition to
      the age-related decline in hippocampal formation (HF) activation (p < .05; false
      discovery ratesmall volume correction-HF-region of interest), we observed an age
      by WWC1 genotype interaction on HF activation during encoding and retrieval. The
      CC group showed a significant negative association between HF activity and
      increasing age, while no such association was observed in the T carrier group
      (left HF p = .04; r-z correlation difference during encoding and retrieval; right
      HF p = .0008; r-z correlation difference during retrieval). CONCLUSIONS: Our
      results show a dynamic relationship between rs17070145 polymorphism and
      increasing age on neuronal activity in the hippocampal region.

PMID- 24290730
TI  - Emergence of a large pore subpopulation during electroporating pulses.
AB  - Electroporation increases ionic and molecular transport through cell membranes by
      creating transient aqueous pores. These pores cannot be directly observed
      experimentally, but cell system modeling with dynamic electroporation predicts
      pore populations that produce cellular responses consistent with experiments. We
      show a cell system model's response that illustrates the life cycle of a pore
      population in response to a widely used 1 kV/cm, 100 MUs trapezoidal pulse. Rapid
      pore creation occurs early in the pulse, followed by the gradual emergence of a
      subpopulation of large pores reaching ~30 nm radius. After the pulse, pores
      rapidly contract to form a single thermally broadened distribution of small pores
      (~1 nm radius) that slowly decays. We also show the response of the same model to
      pulses of 100 ns to 1 ms duration, each with an applied field strength adjusted
      such that a total of 10,000+/-100 pores are created. As pulse duration is
      increased, the pore size distributions vary dramatically and a distinct
      subpopulation of large pores emerges for pulses of microsecond and longer
      duration. This subpopulation of transient large pores is relevant to
      understanding rapid transport of macromolecules into and out of cells during a
      pulse.

PMID- 24290731
TI  - Becoming a caring nurse--a Nordic study on students' learning and development in
      clinical education.
AB  - The aim of this study was to elucidate the meaning and deepen the understanding
      of student learning and development in becoming a nurse. Data were collected from
      focus group interviews with students from three different universities and
      analysed using a phenomenological-hermeneutical method. The comprehensive
      understanding of student learning and development in becoming a nurse resulted in
      two constituents: the prerequisites for learning and development, and itineraries
      for learning and development. The prerequisites consisted of a caring
      relationship as the foundation for learning and development, and will and
      motivation for learning and development. The itineraries for learning and
      development involved pushing boundaries through challenges and support, and of a
      synthesis of theory and praxis through reflection. Caring relationships can be
      seen as the foundation for student learning and development and as a prerequisite
      for becoming a nurse. Learning is not merely a skills-acquisition procedure but a
      transforming experience for students, who feel that their whole existence has
      been altered. It is time to move beyond examining student learning and
      development merely from an epistemological perspective and start focussing on the
      ontological aspect of learning, on the processes of transformation and becoming a
      nurse.

PMID- 24290732
TI  - High or conventional positive end-expiratory pressure in adult respiratory
      distress syndrome.
AB  - Patients with acute respiratory distress syndrome may require high positive end
      expiratory pressure (PEEP) levels, though the optimum level remains to be
      established. Several clinical trials have compared high PEEP levels versus
      conventional PEEP. Overall, although high PEEP levels improve oxygenation and are
      safe, they do not result in a significant reduction of the mortality rates.
      Nevertheless, some metaanalyses have revealed 2 situations in which high PEEP may
      decrease mortality: When used in severe distress and when PEEP is set following
      the characteristics of lung mechanics. Five studies have explored this latter
      scenario. Unfortunately, all of them have small sample sizes and have used
      different means to determine optimum PEEP. It is therefore necessary to conduct
      studies of sufficient sample size to compare the treatment of patients with
      severe acute respiratory distress syndrome, using a protective ventilation
      strategy with high PEEP guided by the characteristics of lung mechanics and
      ventilation with the protocol proposed by the ARDS Network.

PMID- 24290733
TI  - Hydromorphone: evolving to meet the challenges of today's health care
      environment.
AB  - BACKGROUND: Hydromorphone, a potent analogue of morphine, has long had an
      important role in pain management and is included in several international
      guidelines for managing pain. Advances in hydromorphone formulations and the ways
      in which hydromorphone is being used clinically today warrant a review of the
      drug's pharmacotherapeutic utility. OBJECTIVE: The history and recent advances in
      hydromorphone pharmacotherapy are reviewed. Areas covered include the
      pharmacologic and metabolic profile of hydromorphone, the role of hydromorphone
      in pain management, formulations and routes of administration, and issues related
      to relative opioid potencies, equianalgesic ratios, and opioid rotation. Because
      hydromorphone, like all opioids, carries a risk of misuse, abuse, and illicit
      diversion, the related issues of tamper-resistant formulations and "dose-dumping"
      of extended-release formulations are discussed. CONCLUSIONS: Due to the epidemic
      of prescription opioid overdoses associated with prescription opioid abuse in the
      United States, development of tamper-resistant opioid formulations that avoid
      dose-dumping issues has become a significant goal of pharmaceutical
      manufacturers. The current formulation of hydromorphone extended-release
      potentially provides the benefits of long-acting hydromorphone (ie, continuous
      pain control, increased quality of life, freedom to perform daily activities) to
      appropriate patients, while reducing the risks of abuse and without compromising
      safety.

PMID- 24290734
TI  - Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation
      and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover
      study in patients with advanced cancer.
AB  - BACKGROUND: Preclinical studies comparing paclitaxel formulated with
      polyethoxylated castor oil with the sonicated formulation of liposome-entrapped
      paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity
      while maintaining similar efficacy. Preliminary studies on the pharmacokinetics
      in patients support earlier preclinical data, which suggested that the LEP Easy
      to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have
      comparable pharmacokinetic properties. OBJECTIVES: Our objectives were: (1) to
      determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU
      (test) and paclitaxel formulated with castor oil (reference); and (2) to assess
      the tolerability of LEP-ETU following intravenous administration. METHODS:
      Patients with advanced cancer were studied in a randomized, 2-period crossover
      bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an
      intravenous infusion over 180 minutes, either as a single-treatment cycle of the
      test formulation followed by a single-treatment cycle of the reference
      formulation, or vice versa. RESULTS: Thirty-two of 58 patients were evaluable and
      were included in the analysis for bioequivalence. Mean total paclitaxel Cmax
      values for the test and reference formulations were 4955.0 and 5108.8 ng/mL,
      respectively. Corresponding AUC0-infinity values were 15,853.8 and 18,550.8
      ng.h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI,
      91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-infinity. These results met
      the required 80% to 125% bioequivalence criteria. The most frequently reported
      adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia.
      CONCLUSION: At the studied dose regimen, LEP-ETU showed bioequivalence with
      paclitaxel formulated with polyethoxylated castor oil.

PMID- 24290735
TI  - Economic burden of adverse events in patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: Although targeted therapies (ie, tyrosine kinase inhibitors and
      antiangiogenesis agents) are effective as first-line treatment of metastatic
      renal cell carcinoma (mRCC), moderate-to-severe adverse events have been reported
      in clinical trials of these agents. Information concerning the economic burden of
      these events is limited. OBJECTIVE: The purpose of this study was estimate the
      costs associated with adverse events in patients with mRCC receiving selected
      targeted agents indicated for first-line treatment of this disease. METHODS:
      Retrospective study based on health care claims data for patients with mRCC, aged
      >=18 years, receiving first-line treatment with targeted therapies. Adverse
      events of interest included abdominal pain, back pain, diarrhea, dyspnea,
      extremity pain, fatigue and/or asthenia, hand-foot syndrome, hypertension,
      lymphopenia, nausea and/or vomiting, neutropenia, proteinuria, and
      thrombocytopenia. Patients receiving care for these events were identified using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) diagnosis and procedure codes on health care claims. Costs were
      examined during a 30-day period, beginning with date of first mention of each
      event; nonevented patients similarly were assigned a shadow index date. We
      estimated total costs during 30 days after the index date for patients with and
      without adverse events, excluding the costs of targeted therapy. RESULTS: Sixty
      four percent of patients receiving targeted therapies for mRCC had health care
      encounters for >=1 adverse events. Events that occurred with a frequency >20%
      included severe abdominal pain, back pain, fatigue and/or asthenia, and nausea
      and/or vomiting, respectively; 10% to 20% of patients had encounters for
      diarrhea, dyspnea, and extremity pain, respectively. Mean (SD) total costs of
      care during the 30-day, postevent period were substantially higher among patients
      with versus without adverse events-$12,177 ($19,621) versus $4070 ($8142).
      Adjusting for differences in baseline characteristics, the estimated cost
      difference was $11,373 (95% CI, $5286-$21,419). CONCLUSIONS: Costs of adverse
      events are substantial in patients receiving targeted therapies, specifically,
      sunitinib, sorafenib, or bevacizumab, for mRCC. Efforts to prevent and/or better
      manage these events may reduce health care costs.

PMID- 24290736
TI  - Is it possible to withdraw biologics from therapy in rheumatoid arthritis?
AB  - BACKGROUND: Biologic agents targeting tumor necrosis factor (TNF) have
      revolutionized the treatment of rheumatoid arthritis (RA). Clinical remission is
      perceived as a realistic primary goal, and its maintenance leads to structural
      and functional remission. OBJECTIVE: This study reviews whether discontinuation
      of biologic agents is possible after sustained remission and discusses its
      significance from the risk/benefit point of view (including safety and health
      economic considerations). METHODS: Using a strategic PubMed search, 45 original
      research articles regarding discontinuation of biologic agents were identified; 7
      were selected that had an obvious focus on discontinuation of biologic agents.
      These articles included the TNF20, BeSt (Behandel Strategieen), and RRR
      (Remission Induction by Remicade in RA) studies. However, because of the
      limitations of the original search, we also review here some articles that did
      not focus mainly on discontinuation of biologic agents but that presented data
      regarding biologic-free control. These studies included OPTIMA (Optimal Protocol
      for Treatment Initiation With MTX and Adalimumab), PRESERVE, and CERTAIN, as well
      as some recent findings in the HONOR (Humira Discontinuation Without Functional
      and Radiographic Damage Progression Following Sustained Remission) study from our
      department. RESULTS: In BeSt and OPTIMA, clinical remission was sustained without
      functional progression by discontinuing TNF inhibitors, after reducing disease
      activity by using TNF inhibitors and methotrexate (MTX), in patients with early
      RA and who were MTX naive. In some studies (including RRR and HONOR), the
      discontinuation of TNF inhibitors after sustained remission was possible in some
      patients with long-standing RA who had an inadequate response to MTX. When
      disease activity flared up after treatment discontinuation, re-treatment with
      infliximab or adalimumab was highly effective and safe in the majority of
      patients. It is also clear that tight control with TNF inhibitors and MTX seems
      to be a prerequisite for having a better chance of biologic-free remission.
      CONCLUSIONS: Intensive treatment with TNF inhibitors may change the disease
      process of RA and potentially offers the possibility of a "treatment holiday"
      from biologic agents.

PMID- 24290737
TI  - Cardiac repolarization with Gabapentin enacarbil in a randomized, double-blind,
      placebo- and active-controlled, crossover thorough QT/QTc study in healthy
      adults.
AB  - BACKGROUND: Gabapentin enacarbil (GEn) is a prodrug of gabapentin and is approved
      in the United States in adults for the management of postherpetic neuralgia and
      in the United States and Japan for the treatment of moderate-to-severe primary
      restless legs syndrome. OBJECTIVE: This study examined the lack of effect of GEn
      on cardiac repolarization in accordance with International Conference on
      Harmonisation E14 guidance. METHODS: This was a randomized, double-blind, double
      dummy, placebo- and active- controlled, crossover study in healthy adults (age
      range, 18-50 years). Study participants received the following in randomized
      order with a minimum 7-day washout period between treatments: placebo at 0 hours
      and GEn 1200 mg at 2 hours (GEn 1200 mg group), placebo at 0 hours and GEn 6000
      mg at 2 hours (GEn 6000 mg group), placebo at 0 and 2 hours (placebo group),
      moxifloxacin 400 mg (active control group) at 0 hours, and placebo at 2 hours
      (moxifloxacin group). Dose offsetting permitted moxifloxacin to be administered
      in the fasted state and GEn to be administered in the fed state. Assessments
      included continuous ECG monitoring, pharmacokinetic parameters, and safety and
      tolerability profiles. The primary end point was the change from baseline in the
      Fridericia corrected QT interval, at each time point, for the GEn 6000 mg and
      placebo groups. RESULTS: Of 52 adults enrolled (mean [SD] age, 30.8 [8.55] years;
      50% women), 44 adults (85%) completed the study. Forty-nine adults received GEn
      1200 mg, 47 received GEn 6000 mg, 48 received placebo, and 47 received
      moxifloxacin. The highest estimated (upper limit of the 95% CI) model-adjusted
      difference in mean change from baseline in the Fridericia corrected QT interval
      between GEn and placebo was 3.55 (5.66) msec for 1200 mg and 1.20 (3.32) msec for
      6000 mg. Assay sensitivity was confirmed with moxifloxacin 400 mg. The geometric
      mean (%CV) Cmax (between-subject coefficient of variation) was 7.49 (21.2) MUg/mL
      for GEn 1200 mg, 32.46 (23.9) MUg/mL for GEn 6000 mg, and 2.08 (24.5) MUg/mL for
      moxifloxacin 400 mg. The most frequently reported adverse events with GEn 6000 mg
      were dizziness (30%), feeling drunk (26%), nausea (15%), headache (13%), and
      vomiting (13%). CONCLUSION: Single doses of GEn, up to 6000 mg, had no effect on
      cardiac repolarization in this thorough-QT study and are unlikely to cause
      clinically relevant QT prolongation in clinical use. Assay sensitivity was
      confirmed with moxifloxacin as an active control. ClinicalTrials.gov identifier:
      NCT01516372.

PMID- 24290738
TI  - Total hip arthroplasty using imageless computer-assisted hip navigation: a
      prospective randomized study.
AB  - In a prospective randomized study of two groups of 65 patients each, we compared
      the acetabular component position when using the imageless navigation system
      compared to the freehand conventional technique for cementless total hip
      arthroplasty. The position of the component was determined postoperatively on
      computed tomographic scans of the pelvis. There was no significant difference for
      postoperative mean inclination (P = 0.29), but a significant difference for mean
      postoperative acetabular component anteversion (P = 0.007), for mean deviation of
      the postoperative anteversion from the target position of 15 degrees  (P = 0.02)
      and for the outliers regarding inclination (P = 0.02) and anteversion (P < 0.05)
      between the computer-assisted and the freehand-placement group. Our results
      demonstrate the importance of imageless navigation for the accurate positioning
      of the acetabular component.

PMID- 24290739
TI  - Mail versus telephone administration of the Oxford Knee and Hip Scores.
AB  - Telephone and postal methods of administration of the Oxford Knee Score (OKS) and
      the Oxford Hip Score (OHS) were compared on 85 and 61 patients undergoing total
      knee arthroplasty (TKA) and total hip arthroplasty (THA), respectively. The test
      for equivalence was significant for both the knee (P<0.001) and hip participants
      (P<0.001) indicating that the modes of administration yielded similar results.
      The ICCs of the OKS and OHS were 0.79 (95% Confidence Interval (CI) 0.70, 0.86)
      and 0.87 (0.79, 0.92) respectively. The 95% limits of agreement were wide for
      both scores (OKS LOA, -8.6, 8.2; OHS LOA, -7.7, 5.3). The two modes of
      administration of the OKS and OHS produce equivalent survey responses at a group
      level but the same method of administration should be constant for individual
      monitoring in a clinical setting. 

PMID- 24290740
TI  - The role of oxidative stress in aseptic loosening of total hip arthroplasties.
AB  - This study investigated the hypothesis that wear particle-induced oxidative
      stress initiates osteolysis after total hip arthroplasty (THA). Patient
      radiographs were scored for osteolysis and periprosthetic tissues were
      immunostained and imaged to quantify polyethylene wear, inflammation, and five
      osteoinflammatory and oxidative stress-responsive factors. These included high
      mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric
      oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The
      results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1,
      whereas inflammation only correlated with NT and HMGB1. Similar to wear debris
      and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis
      correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement
      of oxidative stress in wear-induced osteolysis will help identify diagnostic
      biomarkers and therapeutic targets to prevent osteolysis after THA. 

PMID- 24290741
TI  - The effect of rotating platform TKA on strain distribution and torque
      transmission on the proximal tibia.
AB  - Limited experimental data exist comparing the mechanical response of the tibial
      cortex between fixed and rotating platform (RP) total knee arthroplasty (TKA),
      particularly in the revision setting. We asked if RP-TKA significantly affects
      tibiofemoral torque and cortical stain response in both the primary and revision
      settings. Fixed and RP tibial trays were implanted into analogue tibias and
      biomechanically tested under axial and torsional loading. Torque and strain
      response were analyzed using digital image correlation. Fixed bearing designs
      exhibited 13.8 times greater torque (P<0.01), and 69% (P<0.01) higher cortical
      strain than RP designs. Strain response was similar in the primary and revision
      cohorts. The decrease in torque transfer could act as a safeguard to reduce
      stress, micromotion and torsional fatigue in scenario of poor bone stock. 

PMID- 24290742
TI  - Development and preliminary evaluation of a decision aid for disclosure of mental
      illness to employers.
AB  - OBJECTIVE: Many mental health service users delay disclosing to employers or
      never do so due to previous experience of, or anticipation of discrimination.
      However, non-disclosure precludes requesting 'reasonable workplace adjustments'.
      Service users may experience conflicting needs and values in deciding whether to
      disclose. No evidence-based interventions exist to support this decision.
      METHODS: A decision aid (CORAL, or COnceal or ReveAL) to support mental health
      service users in reaching disclosure decisions was developed and subjected to
      preliminary evaluation (n=15). RESULTS: The majority found the decision aid quick
      (60%) and relevant (60%) and would recommend it (80%). Eighty percent reported
      that they would definitely or probably use it in making disclosure decisions.
      Forty percent each were positive or neutral on its ease of use. Semi-structured
      interviews revealed a demand for more information on the legal implications of
      disclosure. The mean level of 'decisional conflict' regarding disclosure reduced
      from 52.0 to 35.5 and mean Stage of Decision-making Scale score from 4.6 to 4.3.
      CONCLUSION: The results suggest that the CORAL decision aid is feasible, relevant
      and valuable in supporting decisions about disclosing a mental illness to an
      employer. PRACTICE IMPLICATIONS: The decision aid could be deployed in routine
      care without significant resource implications.

PMID- 24290743
TI  - Genetic modulation of the SERCA activity does not affect the Ca(2+) leak from the
      cardiac sarcoplasmic reticulum.
AB  - The Ca(2+) content in the sarcoplasmic reticulum (SR) determines the amount of
      Ca(2+) released, thereby regulating the magnitude of Ca(2+) transient and
      contraction in cardiac muscle. The Ca(2+) content in the SR is known to be
      regulated by two factors: the activity of the Ca(2+) pump (SERCA) and Ca(2+) leak
      through the ryanodine receptor (RyR). However, the direct relationship between
      the SERCA activity and Ca(2+) leak has not been fully investigated in the heart.
      In the present study, we evaluated the role of the SERCA activity in Ca(2+) leak
      from the SR using a novel saponin-skinned method combined with transgenic mouse
      models in which the SERCA activity was genetically modulated. In the SERCA
      overexpression mice, the Ca(2+) uptake in the SR was significantly increased and
      the Ca(2+) transient was markedly increased. However, Ca(2+) leak from the SR did
      not change significantly. In mice with overexpression of a negative regulator of
      SERCA, sarcolipin, the Ca(2+) uptake by the SR was significantly decreased and
      the Ca(2+) transient was markedly decreased. Again, Ca(2+) leak from the SR did
      not change significantly. In conclusion, the selective modulation of the SERCA
      activity modulates Ca(2+) uptake, although it does not change Ca(2+) leak from
      the SR. 

PMID- 24290745
TI  - Detection by NeuroSENSE Cerebral Monitor of Two Major Neurologic Events During
      Cardiac Surgery.

PMID- 24290746
TI  - Basic data from 176 studies on the immediate outcome after aortic valve
      replacement with or without coronary artery bypass surgery.
AB  - OBJECTIVE: The aim of this study was to summarize the immediate outcome after
      aortic valve replacement (AVR) with or without coronary artery bypass grafting
      (CABG). DESIGN: Systematic review and meta-analysis. SETTING: University
      hospitals. PARTICIPANTS: Participants were 683,286 patients who underwent AVR
      with or without CABG. Patients undergoing other major cardiac procedures were
      excluded from this analysis. INTERVENTIONS: AVR with or without CABG.
      MEASUREMENTS AND MAIN RESULTS: Operative mortality after AVR with or without
      concomitant CABG was 4.3%, stroke 2.1%, pacemaker implantation 5.9%, and dialysis
      2.2%. After isolated AVR, operative mortality was 3.3%, stroke 1.7%, pacemaker
      implantation 3.3%, and dialysis 1.6%. Mortality was increased among very elderly
      (< 60 years: 3.3%, 60-69 years: 2.7%, 70-79 years: 3.8%,>= 80 years: 6.1%, p <
      0.001). Prevalence of minimally invasive AVR (mini-AVR) was associated with
      significantly lower operative mortality (p = 0.039, 46 studies). Mini-AVR only
      tended toward lower mortality when included in meta-regression analysis as a
      dichotomous variable (mini-AVR 4,367 patients: 2.3%, 95% CI 1.8-2.9% v full
      sternotomy 11,076 patients: 3.5%, 95% CI 28-4.1%, p = 0.088). Operative mortality
      after AVR plus CABG was 5.5% (versus isolated AVR: p < 0.001), stroke 3.0%,
      pacemaker implantation 3.9%, and dialysis 5.6%. Mortality was high in all age
      strata, particularly among very elderly (mean age < 70 years: 4.8%, mean age 70
      79 years: 4.7%; mean age >= 80 years: 8.4%, p = 0.002). CONCLUSIONS: Isolated AVR
      is associated with low mortality and morbidity. Coronary artery disease requiring
      concomitant CABG increases the operative mortality. Patients requiring AVR and
      CABG should be the main target of less-invasive treatment strategies.

PMID- 24290747
TI  - In response.

PMID- 24290744
TI  - Understanding fertilization through intracytoplasmic sperm injection (ICSI).
AB  - Since the establishment of in vitro fertilization, it became evident that almost
      half of the couples failed to achieve fertilization and this phenomenon was
      attributed to a male gamete dysfunction. The adoption of assisted fertilization
      techniques particularly ICSI has been able to alleviate male factor infertility
      by granting the consistent ability of a viable spermatozoon to activate an
      oocyte. Single sperm injection, by pinpointing the beginning of fertilization,
      has been an invaluable tool in clarifying the different aspects of early
      fertilization and syngamy. However, even with ICSI some couples fail to fertilize
      due to ooplasmic dysmaturity in relation to the achieved nuclear maturation
      marked by the extrusion of the first polar body. More uncommon are cases where
      the spermatozoa partially or completely lack the specific oocyte activating
      factor. In this work, we review the most relevant aspects of fertilization and
      its failure through assisted reproductive technologies. Attempts at diagnosing
      and treating clinical fertilization failure are described. 

PMID- 24290748
TI  - Anesthetic considerations for thoracoscopic sympathetic ganglionectomy to treat
      ventricular tachycardia storm: a single-center experience.
AB  - OBJECTIVE: The aim of this study was to determine the pertinent anesthetic
      considerations for patients undergoing surgical sympathectomy for electrical
      storm (incessant ventricular tachycardia (VT) refractory to traditional
      therapies). DESIGN: This is a retrospective review of a prospective database.
      SETTING: This single-center study took place in a university hospital setting.
      PARTICIPANTS: Twenty-six patients were enrolled. INTERVENTIONS: Fifteen patients
      underwent left-sided sympathectomy, whereas 11 patients underwent bilateral
      sympathectomy. MEASUREMENTS AND MAIN RESULTS: Anesthetic management of these
      patients was quite complex, requiring invasive monitoring, transesophageal
      echocardiography, one-lung ventilation, programming of cardiac rhythm management
      devices, and titration of vasoactive medications. Paired t test of hemodynamic
      data before, during, and after surgery showed no significant difference between
      preoperative and postoperative blood pressure values, regardless of whether the
      patient underwent unilateral or bilateral sympathectomy. Eight patients remained
      free of VT, three patients responded well to titration of oral medications, and
      one patient required 2 radiofrequency ablations after sympathectomy to control
      his VT. Three patients continued to have VT episodes, although reduced in
      frequency compared with before the procedure. Four patients were lost to
      followup. Overall, five patients within the cohort died within 30 days of the
      procedure. No patients developed any anesthetic complications or Horner's
      syndrome. The overall perioperative mortality (within the first 7 days of the
      procedure) was 2 of 26, or 7.7%. CONCLUSIONS: The anesthetic management of
      patients undergoing surgical sympathectomy for electrical storm can be quite
      complex, because these patients often present in a moribund and emergent state
      and cannot be optimized using current ACC/AHA guidelines. Expertise in invasive
      monitoring, transesophageal echocardiography, one-lung ventilation, cardiac
      rhythm device management, and pressor management is crucial for optimal
      anesthetic care.

PMID- 24290749
TI  - Use of partial venovenous cardiopulmonary bypass in percutaneous hepatic
      perfusion for patients with diffuse, isolated liver metastases: a case series.
AB  - OBJECTIVES: Diffuse isolated liver metastases are the dominant mode of tumor
      progression in a number of cancers and present a major treatment challenge for
      oncologists. An experimental treatment, percutaneous hepatic perfusion (PHP),
      utilizes partial venovenous cardiopulmonary bypass to allow administration of
      high-dose chemotherapy directly and solely to the liver with filtration of
      chemotherapeutic agents from the blood prior to its return to the systemic
      circulation, thereby minimizing toxic systemic effects. The following case series
      describes the management of 5 patients with metastatic melanoma undergoing serial
      PHPs. DESIGN: A single-center experience from a national multi-center random
      assignment trial comparing PHP to best alternative care (BAC) in patients with
      diffuse melanoma liver metastases. SETTING: A tertiary care hospital.
      PARTICIPANTS: Five patients with metastatic melanoma to the liver. INTERVENTION:
      Five patients underwent a total of fifteen PHPs using a venovenous bypass circuit
      with hemofiltration, receiving hepatic intra-arterial melphalan, 3 mg/kg of ideal
      body weight, for 30 minutes with a total of 60 minutes of hemofiltration.
      MEASUREMENTS AND MAIN RESULTS: Five patients tolerated the procedure well with
      transient hemodynamic and metabolic changes. CONCLUSIONS: In patients with
      diffuse isolated liver metastases, PHP is a safe and well-tolerated procedure
      that can be performed more than once and is associated with marked anti-tumor
      activity in some patients.

PMID- 24290750
TI  - Apnea testing for diagnosing brain death during extracorporeal membrane
      oxygenation.

PMID- 24290751
TI  - Prevalence of insulin resistance and cardiometabolic risk in Korean children and
      adolescents: a population-based study.
AB  - AIMS: We aimed to establish normal reference values of serum insulin and the
      homeostasis model assessment of insulin resistance (HOMA-IR). We also aimed to
      verify HOMA-IR "cut-off values" in predicting cardiometabolic risk among Korean
      children and adolescents. METHODS: Data from 2716 Korean subjects (1421 male and
      1295 female, aged 10-20 years) were evaluated. Insulin resistance was defined as
      HOMA-IR >95th percentile. The odds ratios of cardiometabolic risk were assessed
      based on the state of insulin resistance. RESULTS: Reference values of insulin
      and HOMA-IR were determined according to sex and age, based on data obtained from
      normal-weight subjects with normal fasting glucose levels. HOMA-IR values
      appeared to peak at the age of 14-15 years in male subjects and at the age of 12
      13 years in female subjects. The prevalence of insulin resistance in the subjects
      was 9.8% (male=10.9%, female=8.6%). The prevalence of insulin resistance in
      normal-weight, overweight, and obese subjects were 4.7%, 25.6%, and 47.1%
      respectively. Subjects with insulin resistance had a higher prevalence of
      metabolic syndrome (odds ratios=18.33; 95% confidence interval, 9.62-34.94) and
      its components, especially hyperglycemia and hypertriglyceridemia. CONCLUSION: We
      established reference values of serum insulin and HOMA-IR according to age and
      sex. Obesity is the most important risk factor for insulin resistance and
      metabolic syndrome. However, insulin resistance independently increases
      cardiometabolic risk. This information may be useful for Korean as well as other
      Asian in planning programs for the prevention of type 2 diabetes.

PMID- 24290753
TI  - UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic.
AB  - The phenomenon of white fat "browning," in which certain white adipose tissue
      depots significantly increase gene expression for the uncoupling protein UCP1 and
      thus supposedly acquire thermogenic, fat-burning properties, has attracted
      considerable attention. Because the mRNA increases are from very low initial
      levels, the metabolic relevance of the change is unclear: is the UCP1 protein
      thermogenically competent in these brite/beige-fat mitochondria? We found that,
      in mitochondria isolated from the inguinal "white" adipose depot of cold
      acclimated mice, UCP1 protein levels almost reached those in brown-fat
      mitochondria. The UCP1 was thermogenically functional, in that these mitochondria
      exhibited UCP1-dependent thermogenesis with lipid or carbohydrate substrates with
      canonical guanosine diphosphate (GDP) sensitivity and loss of thermogenesis in
      UCP1 knockout (KO) mice. Obesogenic mouse strains had a lower thermogenic
      potential than obesity-resistant strains. The thermogenic density (UCP1-dependent
      oxygen consumption per g tissue) of inguinal white adipose tissue was maximally
      one-fifth of interscapular brown adipose tissue, and the total quantitative
      contribution of all inguinal mitochondria was maximally one-third of all
      interscapular brown-fat mitochondria, indicating that the classical brown adipose
      tissue depots would still predominate in thermogenesis. 

PMID- 24290752
TI  - Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.
AB  - Autophagy dysfunction has been implicated in misfolded protein accumulation and
      cellular toxicity in several diseases. Whether alterations in autophagy also
      contribute to the pathology of lipid-storage disorders is not clear. Here, we
      show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with
      cholesterol accumulation, where the maturation of autophagosomes is impaired
      because of defective amphisome formation caused by failure in SNARE machinery,
      whereas the lysosomal proteolytic function remains unaffected. Expression of
      functional NPC1 protein rescues this defect. Inhibition of autophagy also causes
      cholesterol accumulation. Compromised autophagy was seen in disease-affected
      organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-beta
      cyclodextrin, which is used for cholesterol-depletion treatment, impedes
      autophagy, whereas stimulating autophagy restores its function independent of
      amphisome formation. Our data suggest that a low dose of HP-beta-cyclodextrin
      that does not perturb autophagy, coupled with an autophagy inducer, may provide a
      rational treatment strategy for NPC1 disease. 

PMID- 24290754
TI  - Combined Wnt/beta-catenin, Met, and CXCL12/CXCR4 signals characterize basal
      breast cancer and predict disease outcome.
AB  - Prognosis for patients with estrogen-receptor (ER)-negative basal breast cancer
      is poor, and chemotherapy is currently the best therapeutic option. We have
      generated a compound-mutant mouse model combining the activation of beta-catenin
      and HGF (Wnt-Met signaling), which produced rapidly growing basal mammary gland
      tumors. We identified the chemokine system CXCL12/CXCR4 as a crucial driver of
      Wnt-Met tumors, given that compound-mutant mice also deficient in the CXCR4 gene
      were tumor resistant. Wnt-Met activation rapidly expanded a population of cancer
      propagating cells, in which the two signaling systems control different
      functions, self-renewal and differentiation. Molecular therapy targeting Wnt,
      Met, and CXCR4 in mice significantly delayed tumor development. The expression of
      a Wnt-Met 322 gene signature was found to be predictive of poor survival of human
      patients with ER-negative breast cancers. Thus, targeting CXCR4 and its upstream
      activators, Wnt and Met, might provide an efficient strategy for breast cancer
      treatment. 

PMID- 24290755
TI  - Specification of functional cranial placode derivatives from human pluripotent
      stem cells.
AB  - Cranial placodes are embryonic structures essential for sensory and endocrine
      organ development. Human placode development has remained largely inaccessible
      despite the serious medical conditions caused by the dysfunction of placode
      derived tissues. Here, we demonstrate the efficient derivation of cranial
      placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor
      Noggin, a component of the dual-SMAD inhibition strategy of neural induction,
      triggers placode induction at the expense of CNS fates. Concomitant inhibition of
      fibroblast growth factor signaling disrupts placode derivation and induces
      surface ectoderm. Further fate specification at the preplacode stage enables the
      selective generation of placode-derived trigeminal ganglia capable of in vivo
      engraftment, mature lens fibers, and anterior pituitary hormone-producing cells
      that upon transplantation produce human growth hormone and adrenocorticotropic
      hormone in vivo. Our results establish a powerful experimental platform to study
      human cranial placode development and set the stage for the development of human
      cell-based therapies in sensory and endocrine disease. 

PMID- 24290756
TI  - An IKKalpha-nucleophosmin axis utilizes inflammatory signaling to promote genome
      integrity.
AB  - The inflammatory microenvironment promotes skin tumorigenesis. However, the
      mechanisms by which cells protect themselves from inflammatory signals are
      unknown. Downregulation of IKKalpha promotes skin tumor progression from
      papillomas to squamous cell carcinomas, which is frequently accompanied by
      genomic instability, including aneuploid chromosomes and extra centrosomes. In
      this study, we found that IKKalpha promoted oligomerization of nucleophosmin
      (NPM), a negative centrosome duplication regulator, which further enhanced NPM
      and centrosome association, inhibited centrosome amplification, and maintained
      genome integrity. Levels of NPM hexamers and IKKalpha were conversely associated
      with skin tumor progression. Importantly, proinflammatory cytokine-induced
      IKKalpha activation promoted the formation of NPM oligomers and reduced
      centrosome numbers in mouse and human cells, whereas kinase-dead IKKalpha blocked
      this connection. Therefore, our findings suggest a mechanism in which an IKKalpha
      NPM axis may use inflammatory signals to suppress centrosome amplification,
      promote genomic integrity, and prevent tumor progression. 

PMID- 24290757
TI  - Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA
      binding proteins, and are neurotoxic.
AB  - The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common
      genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia
      (FTD). Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues,
      suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression
      of 38* and 72* G4C2 repeats form intranuclear RNA foci that initiate apoptotic
      cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with
      a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected
      cells. Only hnRNP-H binds directly to G4C2 repeats following RNA
      immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci
      detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2
      repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins.
      We propose that RNA toxicity and protein sequestration may disrupt RNA processing
      and contribute to neurodegeneration. 

PMID- 24290758
TI  - Crystal structure of Prp5p reveals interdomain interactions that impact
      spliceosome assembly.
AB  - The DEAD-box adenosine triphosphatase (ATPase) Prp5p facilitates U2 small nuclear
      ribonucleoprotein particle (snRNP) binding to the intron branch site region
      during spliceosome assembly. We present crystal structures of S. cerevisiae Prp5p
      alone and in complex with ADP at 2.12 A and 1.95 A resolution. The three
      dimensional packing of Prp5p subdomains differs strikingly from that so far
      observed in other DEAD-box proteins: two RecA-like subdomains adopt an "open
      state" conformation stabilized by extensive interactions involving sequences that
      flank the two subdomains. This conformation is distinct from that required for
      ATP hydrolysis. Consistent with this, Prp5p mutations that destabilize
      interdomain interactions exhibited increased ATPase activity in vitro and
      inhibited splicing of suboptimal branch site substrates in vivo, whereas
      restoration of interdomain interactions reversed these effects. We conclude that
      the Prp5p open state conformation is biologically relevant and that disruption of
      the interdomain interaction facilitates a large-scale conformational change of
      Prp5p during U2 snRNP-branch site recognition. 

PMID- 24290759
TI  - Integrin-matrix clusters form podosome-like adhesions in the absence of traction
      forces.
AB  - Matrix-activated integrins can form different adhesion structures. We report that
      nontransformed fibroblasts develop podosome-like adhesions when spread on fluid
      Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal
      adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes,
      the podosome-like adhesions are protrusive and characterized by doughnut-shaped
      RGD rings that surround characteristic core components including F-actin, N-WASP,
      and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions,
      though they lack matrix metalloproteinases that characterize invadopodia and
      podosomes of Src-transformed cells. When nontransformed cells develop force on
      integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers
      (metal lines spaced by 1-2 MUm), these podosomes fail to form and instead form
      focal adhesions. The formation of podosomes on fluid surfaces is mediated by
      local activation of phosphoinositide 3-kinase (PI3K) and the production of
      phosphatidylinositol-(3,4,5)-triphosphate (PIP3) in a FAK/PYK2-dependent manner.
      Enrichment of PIP3 precedes N-WASP activation and the recruitment of RhoA-GAP
      ARAP3. We propose that adhesion structures can be modulated by traction force
      development and that production of PIP3 stimulates podosome formation and
      subsequent RhoA downregulation in the absence of traction force. 

PMID- 24290760
TI  - Exosome secretion is enhanced by invadopodia and drives invasive behavior.
AB  - Unconventional secretion of exosome vesicles from multivesicular endosomes (MVEs)
      occurs across a broad set of systems and is reported to be upregulated in cancer,
      where it promotes aggressive behavior. However, regulatory control of exosome
      secretion is poorly understood. Using cancer cells, we identified specialized
      invasive actin structures called invadopodia as specific and critical docking and
      secretion sites for CD63- and Rab27a-positive MVEs. Thus, inhibition of
      invadopodia formation greatly reduced exosome secretion into conditioned media.
      Functionally, addition of purified exosomes or inhibition of exosome biogenesis
      or secretion greatly affected multiple invadopodia life cycle steps, including
      invadopodia formation, stabilization, and exocytosis of proteinases, indicating a
      key role for exosome cargoes in promoting invasive activity and providing in situ
      signaling feedback. Exosome secretion also controlled cellular invasion through
      three-dimensional matrix. These data identify a synergistic interaction between
      invadopodia biogenesis and exosome secretion and reveal a fundamental role for
      exosomes in promoting cancer cell invasiveness. 

PMID- 24290761
TI  - Quantitative and qualitative proteome characteristics extracted from in-depth
      integrated genomics and proteomics analysis.
AB  - Quantitative and qualitative protein characteristics are regulated at genomic,
      transcriptomic, and posttranscriptional levels. Here, we integrated in-depth
      transcriptome and proteome analyses of liver tissues from two rat strains to
      unravel the interactions within and between these layers. We obtained peptide
      evidence for 26,463 rat liver proteins. We validated 1,195 gene predictions, 83
      splice events, 126 proteins with nonsynonymous variants, and 20 isoforms with
      nonsynonymous RNA editing. Quantitative RNA sequencing and proteomics data
      correlate highly between strains but poorly among each other, indicating
      extensive nongenetic regulation. Our multilevel analysis identified a genomic
      variant in the promoter of the most differentially expressed gene Cyp17a1, a
      previously reported top hit in genome-wide association studies for human
      hypertension, as a potential contributor to the hypertension phenotype in SHR
      rats. These results demonstrate the power of and need for integrative analysis
      for understanding genetic control of molecular dynamics and phenotypic diversity
      in a system-wide manner. 

PMID- 24290762
TI  - RIM1alpha SUMOylation is required for fast synaptic vesicle exocytosis.
AB  - The rapid, activity-dependent quantal presynaptic release of neurotransmitter is
      vital for brain function. The complex process of vesicle priming, fusion, and
      retrieval is very precisely controlled and requires the spatiotemporal
      coordination of multiple protein-protein interactions. Here, we show that
      posttranslational modification of the active zone protein Rab3-interacting
      molecule 1alpha (RIM1alpha) by the small ubiquitin-like modifier 1 (SUMO-1)
      functions as a molecular switch to direct these interactions and is essential for
      fast synaptic vesicle exocytosis. RIM1alpha SUMOylation at lysine residue K502
      facilitates the clustering of CaV2.1 calcium channels and enhances the Ca(2+)
      influx necessary for vesicular release, whereas non-SUMOylated RIM1alpha
      participates in the docking/priming of synaptic vesicles and maintenance of
      active zone structure. These results demonstrate that SUMOylation of RIM1alpha is
      a key determinant of rapid, synchronous neurotransmitter release, and the SUMO
      mediated "switching" of RIM1alpha between binding proteins provides insight into
      the mechanisms underpinning synaptic function and dysfunction. 

PMID- 24290764
TI  - A cost-effective method for estimating di(2-ethylhexyl)phthalate in coastal
      sediments.
AB  - This study describes the development of a new method for the analysis of di(2
      ethylhexyl)phthalate (DEHP) using 0.1-0.3 g of sediment sample, based on matrix
      solid phase dispersion (MSPD) using C18 as dispersant phase (0.4 g) and
      acetonitrile-water as eluting solvent (3.4 mL 1:3.25, v/v). No evaporation step
      is required. 3 mL of extracts were processed on-line by in-tube solid phase
      microextraction (IT-SPME) coupled to capillary liquid chromatography (CapLC) and
      diode array detector (DAD). A short analytical column Zorbax SB C18 (35*0.5 mm, 5
      MUm) provided suitable results. FTIR-ATR was employed for characterizing sediment
      samples and MSPD procedure. The total analysis time was less than 20 min (MSPD
      takes about 10 min). The utility of the described approach has been tested by
      analyzing several real samples. No matrix effect was found. Achieved precision
      was less than 10% for DEHP estimation. Detection limits in samples were 270 and
      90 MUg/kg for 0.1 and 0.3 g of taken sediment, respectively.

PMID- 24290763
TI  - Germ plasm anchoring is a dynamic state that requires persistent trafficking.
AB  - Localized cytoplasmic determinants packaged as ribonucleoprotein (RNP) particles
      direct embryonic patterning and cell fate specification in a wide range of
      organisms. Once established, the asymmetric distributions of such RNP particles
      must be maintained, often over considerable developmental time. A striking
      example is the Drosophila germ plasm, which contains RNP particles whose
      localization to the posterior of the egg during oogenesis results in their
      asymmetric inheritance and segregation of germline from somatic fates in the
      embryo. Although actin-based anchoring mechanisms have been implicated, high
      resolution live imaging revealed persistent trafficking of germ plasm RNP
      particles at the posterior cortex of the Drosophila oocyte. This motility relies
      on cortical microtubules, is mediated by kinesin and dynein motors, and requires
      coordination between the microtubule and actin cytoskeletons. Finally, we show
      that RNP particle motility is required for long-term germ plasm retention. We
      propose that anchoring is a dynamic state that renders asymmetries robust to
      developmental time and environmental perturbations. 

PMID- 24290765
TI  - Effects of large volume injection of aliphatic alcohols as sample diluents on the
      retention of low hydrophobic solutes in reversed-phase liquid chromatography.
AB  - Recent studies showed that injection of large volume of hydrophobic solvents used
      as sample diluents could be applied in reversed-phase liquid chromatography (RP
      LC). This study reports a systematic research focused on the influence of a
      series of aliphatic alcohols (from methanol to 1-octanol) on the retention
      process in RP-LC, when large volumes of sample are injected on the column.
      Several model analytes with low hydrophobic character were studied by RP-LC
      process, for mobile phases containing methanol or acetonitrile as organic
      modifiers in different proportions with aqueous component. It was found that
      starting with 1-butanol, the aliphatic alcohols can be used as sample solvents
      and they can be injected in high volumes, but they may influence the retention
      factor and peak shape of the dissolved solutes. The dependence of the retention
      factor of the studied analytes on the injection volume of these alcohols is
      linear, with a decrease of its value as the sample volume is increased. The
      retention process in case of injecting up to 200MUL of upper alcohols is
      dependent also on the content of the organic modifier (methanol or acetonitrile)
      in mobile phase. 

PMID- 24290766
TI  - Catalyst assisted synthesis of initiator attached silica monolith particles via
      isocyanate-hydroxyl reaction for production of polystyrene bound chromatographic
      stationary phase of excellent separation efficiency.
AB  - Dibutyltin dichloride (DBTDC) was used as a catalyst to chemically bind 4
      chloromehtylphenylisocynate (4-CPI) to porous monolithic silica particles via
      isocyanate-hydroxyl reaction, and the reaction product was reacted with sodium
      diethyldithiocarbamate (SDDC) to yield initiator attached silica monolith
      particles. Reversible addition-fragmentation transfer (RAFT) polymerization was
      taken place on them to result in polystyrene attached silica particles that
      showed excellent separation efficiency when packed in a chromatographic column
      (1.0 mm * 300 mm). The numbers of theoretical plates (N) of 56,500 is better than
      those of any commercially available HPLC or UHPLC column yet.

PMID- 24290767
TI  - High-performance liquid chromatography separation of small molecules on a porous
      poly (trimethylol propane triacrylate-co-N-isopropylacrylamide-co-ethylene
      dimethacrylate) monolithic column.
AB  - A porous monolith was prepared by in situ free-radical polymerization using N
      isopropylacrylamide (NIPAAm) and trimethylol propane triacrylate (TMPTA) as
      functional monomers, ethylene dimethacrylate (EDMA) as crosslinking agent. The
      chemical group of the monolith was assayed by a Fourier transform infrared
      spectroscopy (FT-IR) method and the morphology of optimized monolithic column was
      characterized by scanning electron microscopy (SEM). The mechanical strength and
      permeability have been studied in detail as well. The run-to-run and column-to
      column reproducibility of the retention times were less than 0.9% and 3.0%,
      respectively. Furthermore, the influence of temperature and mobile phase
      composition on the separation of aromatic compounds was investigated. The results
      indicated that poly (trimethylol propane triacrylate-co-N-isopropylacrylamide-co
      ethylenedimethacrylate) (TMPTA-co-NIPAAm-co-EDMA) monolithic column not only had
      high porosity and strong rigidity, but also was a promising tool for analyzing
      small molecule compounds with a short analysis time by controlling the column
      temperature. 

PMID- 24290768
TI  - Use of data linkage to measure the population health effect of non-health-care
      interventions.

PMID- 24290769
TI  - Effect of antithrombotic state on clinical outcomes following angiography
      negative subarachnoid hemorrhage.

PMID- 24290770
TI  - Fecal carriage of multi-drug resistant and extended spectrum beta-lactamases
      producing E. coli in household pigeons, Bangladesh.
AB  - Antibiotic resistance and ESBL constitute a risk to human and animal health.
      Birds residing close to humans could mirror the spectrum of human associated
      antibiotic resistance. Household pigeons were screened in Bangladesh to shed
      light on human associated, as well as, environmental antibiotic resistance.
      Escherichia coli from pigeons (n=150) were tested against 11 antibiotics. 89% E.
      coli isolates were resistant to one or more critically important human
      antibiotics like ampicillin, cefadroxil, mecillinam, ciprofloxacin, gentamicin
      and tigecycline. No carbapenamase-producers were detected and the lower ESBL
      prevalence (5%) in pigeons. ESBL-producing E. coli isolates had blaCTX-M-15
      genes. Pigeons shared some bacterial clones and had bird associated sequence
      types like E. coli ST1408. Fecal carriage of bacteria resistance of critically
      important human antibiotics, together with examples of shared genotypes among
      pigeons, indicate the human-birds and bird to bird transmissions are important in
      the epidemiology of antibiotic resistance.

PMID- 24290771
TI  - Brain creatine depletion in vegetarians? A cross-sectional 1H-magnetic resonance
      spectroscopy (1H-MRS) study.
AB  - The present cross-sectional study aimed to examine the influence of diet on brain
      creatine (Cr) content by comparing vegetarians with omnivores. Brain Cr content
      in the posterior cingulate cortex was assessed by proton magnetic resonance
      spectroscopy (1H-MRS). Dietary Cr intake was assessed by 3 d food recalls.
      Vegetarians had lower dietary Cr intake than omnivores (0.03 (SD 0.01) v. 1.34
      (SD 0.62) g/d, respectively; P=0.005). However, vegetarians and omnivores had
      comparable brain total Cr content (5.999 (SD 0.811) v. 5.917 (SD 0.665) IU,
      respectively; P=0.77). In conclusion, dietary Cr did not influence brain Cr
      content in healthy individuals, suggesting that in normal conditions brain is
      dependent on its own Cr synthesis.

PMID- 24290772
TI  - Influence of age on the correlations of hematological and biochemical variables
      with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate.
AB  - OBJECTIVES: To evaluate the influence of age on the relationships between
      biochemical and hematological variables and stability of erythrocyte membrane in
      relation to the sodium dodecyl sulfate (SDS) in population of 105 female
      volunteers between 20 and 90 years. METHODS: The stability of RBC membrane was
      determined by non-linear regression of the dependency of the absorbance of
      hemoglobin released as a function of SDS concentration, represented by the half
      transition point of the curve (D50) and the variation in the concentration of the
      detergent to promote lysis (dD). RESULTS: There was an age-dependent increase in
      the membrane stability in relation to SDS. Analyses by multiple linear regression
      showed that this stability increase is significantly related to the hematological
      variable red cell distribution width (RDW) and the biochemical variables blood
      albumin and cholesterol. DISCUSSION: The positive association between erythrocyte
      stability and RDW may reflect one possible mechanism involved in the clinical
      meaning of this hematological index.

PMID- 24290773
TI  - Prevalence of pelvic organ prolapse detected at dynamic MRI in women without
      history of pelvic floor dysfunction: comparison of two reference lines.
AB  - AIM: To retrospectively evaluate the prevalence of pelvic organ prolapse as an
      incidental finding on dynamic magnetic resonance imaging (MRI) using two
      different references lines. MATERIALS AND METHODS: Sixty women with symptoms
      unrelated to pelvic floor dysfunction who underwent MRI including a dynamic
      sagittal true fast imaging with steady-state free precession (TrueFISP) sequence
      during straining were identified. Two radiologists in consensus used the
      pubococcygeal line (PCL) and mid-pubic line (MPL) to diagnose and grade prolapse
      in all three pelvic compartments. RESULTS: Cystocele was absent, mild, moderate,
      and severe in 88% (53/60), 7% (4/60), 5% (3/60), and 0% (0/60) of patients,
      respectively, using PCL, versus 78% (47/60), 13% (8/60), 5% (3/60), and 3% (2/60)
      of patients, respectively, using MPL. Vaginal prolapse was absent, mild,
      moderate, and severe in 95% (57/60), 5% (3/60), 0% (0/60), and 0% (0/60) of
      patients, respectively, using PCL, versus 80% (48/60), 17% (10/60), 3% (2/60),
      and 0% (0/60) of patients, respectively, using MPL. Rectal descent was absent,
      mild, moderate, and severe in 63% (38/60), 10% (6/60), 23% (14/60), and 3% (2/60)
      of patients, respectively, using PCL, versus 43% (26/60), 27% (16/60), 27%
      (16/60), and 3% (2/60) of patients, respectively, using MPL. No enterocele,
      peritoneocele, or muscular defect was identified. Two percent (1/60) of patients
      had mild rectocele, 8% (5/60) had abnormal vesico-urethral angle, and 25% (15/60)
      had abnormal levator plate angle. CONCLUSION: In asymptomatic women, dynamic MRI
      identified the greatest degrees of prolapse in the posterior compartment. The MPL
      consistently yielded greater frequency of prolapse than the PCL. Findings of
      pelvic organ prolapse may be observed in asymptomatic patients and are of
      uncertain significance, requiring correlation with clinical and physical
      examination findings.

PMID- 24290774
TI  - Spectrum of imaging findings on MDCT enterography in patients with small bowel
      tuberculosis.
AB  - Abdominal tuberculosis (TB) is the sixth most common extrapulmonary site of
      involvement. The sites of involvement in abdominal tuberculosis, in descending
      order of frequency, are lymph nodes, genitourinary tract, peritoneal cavity, and
      gastrointestinal tract. The radiological armamentarium for evaluating
      tuberculosis of the small bowel (SBTB) includes barium studies (small bowel
      follow-through, SBFT), CT (multidetector CT, CT enterography, and CT
      enteroclysis), ultrasound (sonoenteroclysis), and magnetic resonance imaging
      (MRI; enterography and enteroclysis). In this review, we illustrate the
      abnormalities at MDCT enterography in 20 consecutive patients with SB TB and also
      describe extraluminal findings in these patients. MDCT enterography allows non
      invasive good-quality assessment of well-distended bowel loops and the adjacent
      soft tissues. It displays the thickness and enhancement of the entire bowel wall
      in all three planes and allows examination of all bowel loops, especially the
      ileal loops, which are mostly superimposed. The terminal ileum and ileocaecal
      junction are the most common sites of small bowel involvement in intestinal TB.
      The most common abnormality is short-segment strictures with symmetrical
      concentric mural thickening and homogeneous mural enhancement. Other findings
      include lymphadenopathy, ascites, enteroliths, peritoneal thickening, and
      enhancement. In conclusion, MDCT enterography is a comprehensive technique for
      the evaluation of SB TB. 

PMID- 24290775
TI  - Use of non-linear image blending with dual-energy CT improves vascular
      visualization in abdominal angiography.
AB  - AIM: To evaluate the image quality of dual-energy abdominal computed tomography
      (DECT) angiography (CTA) with a non-linear image blending technique as compared
      with the linear image blending technique and standard single-energy CT (SECT; 120
      kVp SECT) imaging. MATERIALS AND METHODS: Thirty-two patients underwent dual
      source, dual-energy abdominal CTA (80 kVp/140 kVp mode) in the arterial phase to
      generate non-linear image blending and 0.5 linear image blending images.
      Abdominal vessel enhancement, image noise, signal-to-noise ratio (SNR) and
      contrast-to-noise ratio (CNR) were evaluated and compared to the conventional 120
      kVp SECT image sets (n = 29) using repeated-measures analysis of variance (ANOVA)
      with Bonferroni adjustment. Two radiologists assessed subjective vessel
      enhancement in consensus. The effective dose was calculated and compared using
      Student's t-test. RESULTS: The non-linear image blending images were ranked
      highest (over 0.5 linear image blending and 120 kVp SECT images) regarding mean
      vascular attenuation, CNR, SNR, and subjective image quality evaluation (p-values
      ranging from <0.001-0.021). However, there was no significant difference in renal
      artery branch visualization among the three sets of images (p = 0.405). Linear
      image blending images showed improved vascular attenuation (p = 0.011) as
      compared with 120 kVp SECT images, but displayed similar results regarding CNRs
      (p = 0.045) and SNRs (p = 0.053). The effective radiation dose for the DECT
      protocol was much lower than the SECT protocol (p = 0.004). CONCLUSION: The non
      linear image blending technique of 80 kVp/140 kVp DECT improved vascular
      visualization by improving contrast enhancement in abdominal CTA during the
      arterial phase.

PMID- 24290776
TI  - Sonographic appearance of cervical lymphadenopathy due to infectious
      mononucleosis in children and young adults.
AB  - AIM: To depict the grey-scale and Doppler features of cervical lymphadenopathy
      due to infectious mononucleosis (IM) and to compare the findings with other
      benign conditions and lymphoma. MATERIALS AND METHODS: One hundred and four
      patients <30 years old with 138 enlarged lymph nodes (LNs) were enrolled for
      sonographic analysis. These LNs were grouped as: IM LNs (59 LNs in 30 patients),
      lymphoma (30 LNs in 30 patients), bacterial lymphadenitis (24 LNs in 20
      patients), tuberculosis (TB; 14 LNs in 13 patients), and reactive hyperplasia (11
      LNs in 11 patients). Sonographic assessments included shape, echotexture, hilum,
      border, matting, cystic necrosis, calcification, and vascular pattern. For each
      sonographic feature, Fisher's exact test was performed to determine whether the
      difference between IM LNs and any another aetiology were statistically
      significant. RESULTS: IM LNs tended to be round in shape (69%), heterogeneous in
      echotexture (61%), absent of echogenic hilum (66%), indistinct margins (80%),
      bilateral distribution (91%), and matting (83%) [even bilateral matting (66%)],
      and central hilar vascularity (89.8%). On analysis, bilateral matting had the
      highest specificity to IM LNs; however, its sensitivity was relatively low. In
      contrast to IM LNs, TB LNs were more likely to have unilateral matting, cystic
      necrosis, and calcification. Indistinct margins and decreased echogenicity of the
      hilum were more frequently seen in IM LNs than in bacterial LNs. Furthermore,
      central hilar vascularity was a common feature of IM LNs and other benignity,
      which can distinguish these from lymphoma and TB LNs. CONCLUSION: Although an
      individual sonographic feature had considerable overlaps between IM LNs and other
      aetiologies, the combination of several features may be helpful in the diagnosis
      of IM.

PMID- 24290777
TI  - Extrapancreatic findings of IgG4-related disease.
AB  - IgG4-related disease is a systemic fibro-inflammatory condition, which includes
      autoimmune pancreatitis as part of the disease spectrum. Imaging has been
      demonstrated to play a major role in the diagnosis of autoimmune pancreatitis.
      Recognizing the wide spectrum of extrapancreatic manifestations of IgG4-related
      disease coupled with a high clinical index of suspicion will allow for an
      accurate and timely diagnosis to be made, thus avoiding unnecessary invasive
      procedures and ensuring that early effective corticosteroid therapy is commenced.
      This review aims to serve as a concise reference tool for both clinicians and
      radiologists in the diagnosis of extrapancreatic IgG4-related disease.

PMID- 24290778
TI  - Re: Assessment of coronary microvascular dysfunction in hypertrophic
      cardiomyopathy: first-pass myocardial perfusion cardiovascular magnetic resonance
      imaging at 1.5 T.

PMID- 24290779
TI  - Diffusion-weighted MRI for differentiation of benign from malignant lesions in
      the gallbladder.
AB  - AIM: To investigate the value of diffusion-weighted imaging (DWI) for
      differentiating benign from malignant gallbladder lesions. MATERIALS AND METHODS:
      One hundred and twenty-six patients who had undergone magnetic resonance imaging
      (MRI) with DWI, in whom the histopathological diagnosis of their gallbladder
      lesions was confirmed by biopsy or surgery were retrospectively analysed. Thirty
      six malignant and 90 benign lesions were included. Two radiologists categorized
      gallbladder lesions into seven types on two imaging sets [T2-weighted imaging
      (WI) alone and combined T2WI and DWI (b = 800 s/mm(2))] according to the presence
      of wall thickening, layered patterns, morphology of the mass, and diffusion
      restriction. Disagreements were resolved in consensus. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of each imaging set for diagnosing gallbladder carcinoma were calculated. The
      diagnostic performance of each imaging set was calculated using receiver
      operating characteristic (ROC) curve analysis. Additionally, ADC values of
      malignant and benign gallbladder lesions were compared separately for 1.5 and 3 T
      MRI. RESULTS: The sensitivity, specificity, PPV, and NPV of diagnosis at T2WI
      were 97.2%, 86.7%, 74.5%, and 98.7%, respectively. The sensitivity, specificity,
      PPV, and NPV using combined T2WI and DWI were 97.2%, 92.2%, 83.3%, and 98.8%,
      respectively. Diagnostic accuracy for gallbladder carcinoma slightly improved
      after adding DWI, from 0.92 to 0.95 (p < 0.05). ADC values for gallbladder
      carcinoma were significantly lower than those for benign lesions. Mean ADC values
      of malignant and benign lesions were 0.97 +/- 0.25 * 10(-3) and 1.72 +/- 0.56 *
      10(-3) mm(2)/s, respectively, at 1.5 T (p < 0.001), and 1.04 +/- 0.38 * 10(-3)
      and 2.2 +/- 0.72 * 10(-3) mm(2)/s, respectively, at 3 T (p < 0.001). CONCLUSION:
      DWI can improve diagnostic accuracy for differentiating benign from malignant
      gallbladder lesions.

PMID- 24290780
TI  - Non-invasive assessment of liver fibrosis using real-time tissue elastography in
      patients with chronic hepatitis B.
AB  - AIM: To evaluate the utility of the elastic ratio calculated using real-time
      tissue elastography for assessing liver fibrosis in patients with chronic
      hepatitis B (CHB). MATERIALS AND METHODS: Ninety-six patients with CHB were
      enrolled between September 2012 and August 2013. The elastic ratio of the liver
      for the intrahepatic venous small vessel was calculated to measure liver
      stiffness. Diagnostic performance of the elastic ratio and aminotransferase-to
      platelet ratio index (APRI) were compared with histological fibrosis stage at
      liver biopsy. In addition, 45 healthy adult volunteers were participated in intra
      and interobserver reliability studies. RESULTS: There was no significant
      influence of hepatitis B e antigen (HBeAg) status or hepatitis B virus DNA levels
      on the elastic ratio measurements in CHB patients. The elastic ratio was
      significantly correlated with histological fibrosis stage (r = 0.873, p < 0.001).
      Cut-off values were 2.62 for stage 2 and over (S >= 2), 3.20 for state 3 and
      over, and 3.86 for stage 4, respectively. The areas under the receiver operating
      characteristic (ROC) curves for elastic ratio and APRI diagnosis of significant
      fibrosis (S >= 2) was 0.91 (95% CI: 0.84-0.98) and 0.71 (95% CI: 0.57-0.86), and
      0.94 (95% CI: 0.89-0.99) and 0.81 (95% CI: 0.71-0.91) for cirrhosis (S = 4),
      respectively. The elastic ratio measurements had good reproducibility: 0.838 for
      intra-observer reliability and 0.805 for inter-observer reliability, respectively
      (p < 0.001). CONCLUSION: Elastic ratio determined using real-time tissue
      elastography was an accurate and reproducible method for evaluating liver
      fibrosis in patients with CHB.

PMID- 24290781
TI  - An individualized contrast material injection protocol with respect to patient
      related factors for dual-source CT coronary angiography.
AB  - AIM: To optimize contrast media (CM) injection protocols by individually
      tailoring the dose to the patient's body weight (BW), body mass index (BMI) and
      heart rate (HR) at dual-source computed tomography coronary angiography (DSCT
      CA). MATERIALS AND METHODS: A total of 423 patients were prospectively enrolled
      and were randomly assigned to four groups. The control group received 80 ml CM at
      5 ml/s. For the HR-optimized group, the injection duration was the same as the
      scan duration plus 8 s. In the Body-optimized group, the dose of CM was tailored
      to BW and BMI. In the HR + Body-optimized group, CM protocols tailored to body
      size and scan duration were applied. Individual variability of arterial
      attenuation and incidence of arterial over-opacification (attenuation >500 HU) in
      the four groups were compared. Correlations between BW, BMI, HR, and arterial
      attenuations were evaluated in the four groups, respectively. RESULTS: Reduced
      individual variability of arterial attenuation and a significantly lower
      incidence of arterial over-opacification were found in the Body-optimized group
      and HR + Body-optimized group. Arterial attenuation was inversely correlated with
      BW, BMI, and HR in the control group, inversely correlated with BW and BMI in the
      HR-optimized group, and inversely correlated with HR in the Body-optimized group.
      In the HR + Body-optimized group, arterial attenuation was not significantly
      correlated with BW, BMI, or HR respectively. CONCLUSION: CM protocols
      individually tailored to BW, BMI, and HR can lead to reduced individual
      variability and a lower incidence of over-opacification of arterial attenuation,
      but also can reduce the influence of BW, BMI, and HR on arterial attenuations at
      DSCT-CA.

PMID- 24290782
TI  - Sudden, unexpected infant death due to pulmonary arterial hypertension.
AB  - A 3-year-old girl with no particular medical history complained of a stomachache
      and died on the way to the hospital. The autopsy revealed marked right
      ventricular hypertrophy and dilation with no other cardiac abnormalities.
      Microscopically, the pulmonary small arteries showed marked medial hypertrophy
      and varying degrees of intimal and adventitial thickening. We supposed that the
      cause of death was attributable to pulmonary arterial hypertension (PAH). PAH is
      a rare disease that can cause sudden, unexpected death at any age. Forensic
      pathologists should consider PAH in the differential diagnosis of sudden death. 

PMID- 24290783
TI  - Gender differences and frequency of whole blood donation in Italian donors: even
      though I want to, I cannot?
AB  - Women are under-represented among blood donors and this difference is
      particularly strong in Italy. This study explore the reasons for the gender gap
      using a sample of donors who had stopped donating at least two years previously
      and analyzing the role of frequency of donation. No significant gender
      differences emerged between the reasons provided by subjects but Italy was the
      country with the longest prescribed interval between whole blood donations for
      women. The gender gap is related to the lengthy interval between successive
      donations of whole blood and reducing this interval could help increase the
      proportion of women donors. 

PMID- 24290784
TI  - The fish tail as a derivation from axial musculoskeletal anatomy: an integrative
      analysis of functional morphology.
AB  - The adult morphology of the tail varies greatly among extant fishes despite
      sharing both ontogenetic similarities and the functional need to propel the body
      through a fluid medium. Both sharks (Chondrichthyes) and ray-finned fishes
      (Actinopterygii) control caudal fin musculature independently of axial body
      myomere activity to modify the stiffness and shape of their tails. For example,
      sharks and bony fishes possess different structural elements and muscles and move
      their tails in different ways, resulting in different locomotory hydrodynamic
      effects and a range of performance variables including speed and maneuverability.
      The stiffness of the heterocercal, lobate tail of the shark can be modulated
      during the tail beat resulting in nearly continuous thrust production. In
      contrast, the highly flexible tail of ray-finned fishes can be manipulated into
      many different shape conformations enabling increased maneuverability for these
      fishes. Consequently, the developmental, morphological, and functional derivation
      of the tail from the axial trunk has resulted in a diversity of form, the
      attributes of which may be of ecological and evolutionary significance. 

PMID- 24290785
TI  - Modular functional organisation of the axial locomotor system in salamanders.
AB  - Most investigations on tetrapod locomotion have been concerned with limb
      movements. However, there is compelling evidence that the axial musculoskeletal
      system contributes to important functions during locomotion. Adult salamanders
      offer a remarkable opportunity to examine these functions because these
      amphibians use axial undulations to propel themselves in both aquatic and
      terrestrial environments. In this article, we review the currently available
      biological data on axial functions during various locomotor modes in salamanders.
      We also present data showing the modular organisation of the neural networks that
      generate axial synergies during locomotion. The functional implication of this
      modular organisation is discussed. 

PMID- 24290786
TI  - [Quality of the anesthesiologist written record during the transfer of
      postoperative patients: Influence of implementing a structured communication
      tool].
AB  - OBJECTIVE: The lack of communication is a major cause of health care errors,
      especially during patient transfer between practitioners and/or healthcare units,
      when standardization of communication is a recommended practice. In our study we
      wanted to assess whether the application of the structured communication SBAR
      tool could influence the quality of the information written on the progress sheet
      by the anesthesiologist involved in the transfer of the patient after surgery.
      MATERIAL AND METHODS: This is an observational, retrospective, randomized,
      quality review of the written record made by the anesthesiologist during the
      transfer of patients from the surgical area to the postoperative recovery unit,
      by applying a validated list. We evaluated three observation periods: a control
      period of two months in 2011 (preSBAR) and a second period of two months in 2012
      (postSBAR); in the latter two groups of patients were transferred (postSBAR +) or
      without SBAR (postSBAR-). RESULTS: The strength of agreement between raters
      obtained an intraclass correlation coefficient of 0.8459 (p <0.001). There were
      significant differences in the study group, with highest average score in the
      group with SBAR (postSBAR + group: mean +/- SD 7.56 +/- 1.20 versus postSBAR
      group: 5.41 +/- 2.98, p <0.001) and depending on the anesthesiologist responsible
      for the intervention participated in the study (mean +/- SD: 7.00 +/- 1.99,
      compared to 4.81 +/- 3.24 in the non-participants, p <0.001). CONCLUSIONS: There
      was an improvement in the quality of written records made in 2012 during the
      implementation of the SBAR, without the actual application of this instrument
      appearing to influence it. The anesthesiologists that were involved in new forms
      of patient safety were also those who made written records of highest quality.

PMID- 24290787
TI  - Lattice imaging at an accelerating voltage of 30kV using an in-lens type cold
      field-emission scanning electron microscope.
AB  - We reported investigation of lattice resolution imaging using a Hitachi SU9000
      conventional in-lens type cold field emission scanning electron microscope
      without an aberration corrector at an accelerating voltage of 30kV and discuss
      the electron optics and optimization of observation conditions for obtaining
      lattice resolution. It is possible to visualize lattice spacings that are much
      smaller than the diameter of the incident electron beam through the influence of
      the superior coherent performance of the cold field emission electron source. The
      defocus difference between STEM imaging and lattice imaging is found to increase
      with spherical aberration but it is possible to reduce the spherical aberration
      by reducing the focal length (f) of the objective lens combined with an
      experimental sample stage enabling a shorter distance between the objective lens
      pre-field and the sample. We demonstrate that it is possible to observe the STEM
      image and crystalline lattice simultaneously. STEM and Fourier transform images
      are detected for Si{222} lattice fringes and reflection spots, corresponding to
      0.157nm. These results reveal the potential and possibility for a measuring
      technique with excellent precision as a theoretically exact dimension and
      established the ability to perform high precision measurements of crystal
      lattices for the structural characterization of semiconductor materials with
      minimal radiation beam damage. 

PMID- 24290788
TI  - An epidemiologic analysis of clinical practice guidelines for non-arthroplasty
      treatment of osteoarthritis of the knee.
AB  - PURPOSE: To analyze the current practice patterns of non-arthroplasty treatment
      of knee osteoarthritis (OA) and to assess the impact of the American Academy of
      Orthopaedic Surgeons clinical practice guidelines on the management of OA of the
      knee, particularly as they relate to the use of arthroscopic treatment. METHODS:
      The United Healthcare Database (2004-2009, 11 million patients, 216 million
      records) was used for the study and was searched using Boolean language for
      International Classification of Diseases, Ninth Edition, Clinical Modification
      and Current Procedural Terminology, fourth revision codes. A reference group was
      defined as patients treated with knee arthroplasty in 2009 and diagnosed with
      knee OA in the same record. Clinical practice patterns in the 5 years preceding
      arthroplasty were analyzed in this group. RESULTS: The reference group consisted
      of 12,806 patients undergoing total knee arthroplasty in 2009 with a documented
      diagnosis of OA at the time of surgery, with prior nonoperative treatment
      strategies analyzed during the preceding 5 years (2004-2009); 10.0% of patients
      were prescribed physical therapy specific to OA, 2.6% received an unloader brace,
      0.52% underwent acupuncture, 43.5% were administered intra-articular
      corticosteroids, and 15.4% received viscosupplementation injections. During the 5
      years before arthroplasty, 2,505 patients (19.6%) underwent arthroscopy and
      debridement/lavage, 35% of whom did not have a diagnosis code for mechanical
      pathology. Within 1 year of knee arthroplasty, 2,028 of the 2,505 knee
      arthroscopies (80.9%) were performed. CONCLUSIONS: The findings show that
      significant gaps do exist between the evidence-based American Academy of
      Orthopaedic Surgeons recommendations and actual practice patterns in the United
      States between 2004 and 2009. LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID- 24290789
TI  - Utility of modern arthroscopic simulator training models.
AB  - PURPOSE: The purpose of this study was to review the published literature on
      modern arthroscopic simulator training models to (1) determine the ability to
      transfer skills learned on the model to the operating room and (2) determine the
      learning curve required to translate such skills. METHODS: A systematic review of
      all studies using PRISMA (Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses) guidelines was performed. Two independent reviewers then analyzed
      studies deemed appropriate for inclusion. Study data collected included
      participant demographic characteristics, simulator model, type and number of
      tasks, method of analysis, and results of training, when available. Given the
      different methods used in each study, descriptive analysis was performed.
      RESULTS: Nineteen studies met the inclusion criteria (9 shoulder, 9 knee, and 1
      hip). A total of 465 participants with a mean age of 30 years were evaluated.
      Twelve studies (63%) compared task performance among participants of different
      experience levels, with 100% reporting a positive correlation between experience
      level and simulator performance. Eight studies (42%) evaluated task performance
      before and after simulator training, with 6 studies showing improvement after
      training; 1 study noted no difference in performance after 1 hour of training.
      One study commented on improved operating room performance after simulator
      training. No studies commented on the number of training sessions needed to
      translate skills learned on the models to the operating room. CONCLUSIONS: This
      review suggests that practice on arthroscopic simulators improves performance on
      arthroscopic simulators. We cannot, however, definitively comment on whether
      simulator training correlates to an improved skill set in the operating room.
      Further work is needed to determine the type and number of training sessions
      needed to translate arthroscopic skills learned on the models to the operating
      room. LEVEL OF EVIDENCE: Level IV, systematic review of studies with Level I
      through IV evidence.

PMID- 24290790
TI  - The use of the ligament augmentation and reconstruction system (LARS) for
      posterior cruciate reconstruction.
AB  - PURPOSE: To systematically review and assess the use of the Ligament Advanced
      Reinforcement System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France)
      for posterior cruciate ligament (PCL) reconstruction. METHODS: A search of
      multiple databases was conducted using the following terms: (LARS[All Fields] AND
      posterior[All Fields]) OR (LARS[All Fields] AND PCL[All Fields]). The
      methodologic quality of each article was assessed by use of abridged Downs and
      Black criteria. RESULTS: Fifty-four studies were found from the database search,
      of which 5 were included in the final review (4 case series and 1 case-control
      study). One hundred twenty-nine PCL reconstructions with LARS were performed. The
      mean patient age was 32.2 years, with 89 male and 40 female patients included.
      The mean follow-up time ranged from 10.5 to 44 months. Lysholm scores improved
      from a mean of 64.8 preoperatively to 89.8 postoperatively. No patients had
      International Knee Documentation Committee grade 1 or 2 preoperatively, with
      93.0% achieving this postoperatively. Only 1 case of synovitis and 1 case of
      graft rupture were reported. CONCLUSIONS: There is little evidence on the
      effectiveness of PCL reconstructions using LARS ligaments. What data there are
      show great promise, with short- and medium-term outcome data appearing favorable
      to autograft reconstruction. Complication rates are encouragingly low. CLINICAL
      RELEVANCE: LARS has great potential for PCL reconstruction. Further studies are
      needed regarding the use of LARS ligaments during PCL reconstruction, including
      longer follow-up periods and investigation into the optimal timing for
      reconstruction. This may be best achieved by way of a multicenter study.

PMID- 24290791
TI  - Unscientific judgment on the Bong-Han theory by an academic authority in the
      USSR.

PMID- 24290792
TI  - Historical observations on the half-century freeze in research between the
      Bonghan system and the primo vascular system.
AB  - This article provides potential reasons for the past 45-year halt in research
      between the time of the Bonghan system of Bong Han Kim (B.H. Kim) and that of the
      primo vascular system (PVS) of Kwang-Sup Soh (K.S. Soh), briefly but more
      accurately in its history. Over the years, numerous questions related to the
      Bonghan system and the PVS have arisen, especially from researchers interested in
      pursuing PVS research: When and how did B.H. Kim's study results on the Bonghan
      system become known to public? Why did B.H. Kim and his publications disappear
      after 1966? Why was little study performed on the system for almost 50 years
      after Kim? Why and how was the research on the system reinitiated in 2002 by
      Kwang-Sup Soh? Why did the Bonghan system become the PVS? These questions, as
      well as technical difficulties in identifying the system, have discouraged many
      researchers from becoming involved in research on the system. The motivation for
      preparing this article was to remove doubts about the existence of this important
      organ, which might have been caused by its unusual and unclear historical
      background, by providing an accurate history. 

PMID- 24290793
TI  - Motion properties of the sanals of the primo vascular system under a magnetic
      field.
AB  - The motion properties of the sanals of the primo vascular system were
      investigated under a low static magnetic field of 100 Oe. Sanals of about 1 MUm
      were selected and separated from the primo vessels and nodes on a rabbit's organ
      surface. The average velocity of five sanals in a physiologic saline solution
      parallel and perpendicular to the direction of the applied magnetic field was
      approximately 1.0 pixel/second in random directions, which implies that the
      rotating motion of sanals with nuclei composed of DNA containing many inorganic
      magnetic elements such as manganese and cobalt is monotonically weakened by
      increasing an applied magnetic field. 

PMID- 24290794
TI  - Primo vessel as a novel cancer cell migration path from testis with nanoparticle
      labeled and GFP expressing cancer cells.
AB  - BACKGROUND/AIM: Recently, a novel circulatory system, the primo vascular system
      (PVS), was found to be a potent metastatic route of cancer cells. The aim of the
      current work is to demonstrate that cancer cells injected into the testis migrate
      through the primo vessel (PV). MATERIALS AND METHODS: NCI-H460 cells labeled with
      fluorescent nanoparticles (FNP) or green fluorescent protein (GFP) gene
      transfection were injected into testicular parenchyma in 24 rats. After 24 hours
      of injection, the abdominal cavity was investigated via a stereomicroscope, to
      detect the PVS, and the samples were analyzed histologically with 4',6-diamidino
      2-phenylindole (DAPI) and hematoxylin and eosin. RESULTS: Injected cancer cells
      were detected inside the PVS distributed on the abdominal organs. Some were
      detected inside intestinal parenchyma into which the attached primo vessels (PVs)
      entered. CONCLUSION: The results supported the fact that the PVS may be a novel
      migration path of cancer cells, in addition to the lymphatic and hematogenous
      routes.

PMID- 24290795
TI  - Primo vascular system floating in lymph ducts of rats.
AB  - An epoch-making development in the gross anatomy of the lymph system has emerged:
      the observation of the primo vascular system (PVS), which is a threadlike
      structure floating in lymph ducts. The PVS, which was proposed as the conduit for
      the acupuncture Qi, is a complex network distributed throughout an animal's body.
      The lymph-PVS, which is a subsystem of the PVS, is one of the most convincing
      visual demonstrations of the PVS. Because its existence is not easily
      demonstrated, even with a microscope, due to its transparency, in current anatomy
      its existence is largely unknown despite its potential significance in physiology
      and medicine. The lymph-PVS has been observed in rabbits, rats, and mice by
      several independent teams. Because the involved techniques are rather
      complicated, we provide detailed protocols for surgery, for injection of the
      staining dye, and for detection, extraction, and identification of the PVS in a
      rat. 

PMID- 24290796
TI  - Formative research on the primo vascular system and acceptance by the korean
      scientific community: the gap between creative basic science and practical
      convergence technology.
AB  - The purpose of this study was to trace the formative process of primo vascular
      system (PVS) research over the past decade and to describe the characteristics of
      the Korean scientific community. By publishing approximately 30 papers in
      journals ranking in the Science Citation Index (Expanded), the PVS research team
      actively convinced domestic and international scientists of the anatomical
      existence of the PVS and its possible application to Korean and Western medicine.
      In addition, by sharing the PVS observation technique, the team promoted the
      dissemination and further pursuit of the research. In 2012, however, PVS
      researchers performed smaller scale research without advancing to a higher level
      as compared to the early days. The main reasons were found to be the Korean
      Research and Development policy of supporting creative, small-scale basic
      research and applied research of Western scientific fields that promised
      potentially greater success on an extensive scale; the indifference concerning,
      and the disbelief in, the existence of a new circulatory system were shown by the
      Western medical community. In addition, the Oriental medical community was
      apathetic about working with the PVS team. Professors Kwang-Sup Soh and Byung
      Cheon Lee were the prime movers of PVS research under difficult conditions.
      Spurred by their belief in the existence and significance of the PVS, they
      continued with their research despite insufficient experimental data. The Korean
      scientific community is not ready to promote the Korea-oriented creative field of
      the PVS team. 

PMID- 24290797
TI  - The primo vascular system as a new anatomical system.
AB  - Traditional Eastern medicine has had a successful existence for a long time and
      has provided functional paths for curing disease. However, some scientists do not
      accept acupuncture, primarily because the meridian system lacks a physical
      anatomical basis. To date, scientific theories have not been able to explain the
      functional paths used by traditional Eastern medicine to cure disease. According
      to Western medicine, no known anatomical foundation exists for the meridians and
      unknown nervous, circulatory, endocrine, and immune mechanisms mediate the
      effects of acupuncture. In the early 1960s, only one hypothesis was proposed to
      explain the anatomical basis of the meridians. By using different experimental
      approaches during the past 10 years, the number of scientific papers that report
      the discovery of different anatomical and physiological evidence confirming the
      existence of an anatomical basis for the meridian system has increased.
      Morphological science is greatly challenged to offer a new biomedical theory that
      explains the possible existence of new bodily systems such as the primo vascular
      system (PVS). The PVS is a previously unknown system that integrates the features
      of the cardiovascular, nervous, immune, and hormonal systems. It also provides a
      physical substrate for the acupuncture points and meridians. Announcements of the
      morphological architectonics and the function of the PVS fundamentally changed
      the basic understanding of biology and medicine because the PVS is involved in
      the development and the functions of living organisms. We propose a new vision of
      the anatomical basis for the PVS and the vital energy-called "Qi"-as an
      electromagnetic wave that is involved very closely with the DNA in the PVS. DNA
      provides genetic information and it functions as a store of information that can
      be obtained from the electromagnetic fields of the environment. The PVS is the
      communication system between living organisms and the environment, and it lies at
      the lowest level of life. The theory of the PVS could be a good basis for forming
      a new point of view of Darwin's evolutionary theory. Discoveries in morphological
      theory-such as discoveries with respect to the PVS-have not been made since the
      18th century. For that reason, the PVS needs more attention. 

PMID- 24290798
TI  - Author reply: To PMID 23084128.

PMID- 24290799
TI  - Cataract surgery in patients with nanophthalmos.

PMID- 24290801
TI  - Comparison of outcomes from a phase 3 study of age-related macular degeneration
      with a matched, observational cohort.
AB  - OBJECTIVE: To compare outcomes of intravitreal therapy from an observational
      study cohort with those of participants receiving treatment in the Minimally
      Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab (MARINA) for the
      treatment of neovascular age-related macular degeneration (wet AMD). DESIGN:
      Database observational study. Participants in the observational cohort were
      chosen to match demographic features and entry criteria of the treatment group
      from MARINA. Outcomes over 12 months were compared. PARTICIPANTS: Eight hundred
      twenty-one anti-vascular endothelial growth factor (anti-VEGF)-naive eyes treated
      with ranibizumab with 12 months or more of follow-up were included in the total
      Fight Retinal Blindness! (FRB-All) cohort, whereas a subset of this cohort of 401
      eyes who were matched to the MARINA treatment group were included as the FRB
      MARINA cohort. INTERVENTION: Intravitreal ranibizumab therapy of 0.5 mg for wet
      AMD. METHODS: Visual acuity (VA) in logarithm of the minimum angle of resolution
      (logMAR) letters and treatments given were recorded continuously and anonymously
      in an electronic database for 12 months. Locally weighted scatterplot smoothing
      (LOESS) regression was used to plot change in visual acuity data over the course
      of 12 months for both the FRB-All cohort and the FRB-MARINA cohort, whereas
      results from the MARINA trial were taken from the published study report. MAIN
      OUTCOME MEASURES: Change in VA in logMAR letters over 12 months, treatment, and
      visit intensity. RESULTS: Mean visual acuity improvement after 12 months in FRB
      MARINA (+5.5 letters) was similar to that of the 0.5-mg group from MARINA (+7.2
      letters). Improvement in FRB-ALL was slightly less (+4.9 letters). Mean treatment
      effect compared with the MARINA control group was similar for the MARINA treated
      group (+17.6 letters) and the FRB-MARINA cohort (+15.9 letters). A mean of 7.3
      injections in 12 months was received by the observational cohorts. CONCLUSIONS:
      Similarity of mean VA improvement in the matched observational cohort with that
      of the phase 3 clinical trial suggests that these results can be achieved in real
      world clinical practice with a modified treatment regimen.

PMID- 24290800
TI  - Retinal blood flow in glaucomatous eyes with single-hemifield damage.
AB  - PURPOSE: To examine the hypotheses that in glaucomatous eyes with single
      hemifield damage, retinal blood flow (RBF) is significantly reduced in the
      retinal hemisphere corresponding with the abnormal visual hemifield and that
      there are significant associations among reduced retinal sensitivity (RS) in the
      abnormal hemifield, RBF, and structural measurements in the corresponding
      hemisphere. DESIGN: Prospective, nonrandomized, case-control study. PARTICIPANTS:
      Thirty eyes of 30 patients with glaucoma with visual field loss confined to a
      single hemifield and 27 eyes of 27 controls. METHODS: Normal and glaucomatous
      eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard
      automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was
      used to measure RBF. The RBF was derived from the recorded Doppler frequency
      shift and the measured angle between the beam and the vessel. Total and
      hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex
      (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis
      of variance and regression analyses were performed. MAIN OUTCOME MEASURES: Total
      and hemispheric RS, RBF, RNFL, and GCC values. RESULTS: The total RBF (34.6+/
      12.2 MUl/minute) and venous cross-sectional area (0.039 +/- 0.009 mm(2)) were
      reduced (P<0.001) in those with glaucoma compared with controls (46.5 +/- 10.6
      MUl/minute; 0.052 +/- 0.012 mm(2)). Mean RBF was reduced in the abnormal
      hemisphere compared with the opposite hemisphere (15.3 +/- 5.4 vs. 19.3 +/- 8.4
      MUl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding
      abnormal hemisphere compared with the opposite hemisphere (87.0 +/- 20.2 vs.
      103.7 +/- 20.6 MUm, P = 0.002; 77.6 +/- 12.1 vs. 83.6 +/- 10.1 MUm, P = 0.04).
      The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P =
      0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF
      (19.3 +/- 8.4 MUl/minute), RNFL (103.7 +/- 20.6 MUm), and GCC (83.6 +/- 10.1 MUm)
      were reduced (P<0.05) in the hemisphere with apparently normal visual field in
      glaucomatous eyes compared with the mean hemispheric values of the normal eyes
      (23.2 +/- 5.3 MUl/minute, 124.8 +/- 9.6 MUm, and 96.1 +/- 5.7 MUm, respectively).
      CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, the RBF is
      significantly reduced in the hemisphere associated with the abnormal hemifield.
      Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal
      hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the
      perimetrically normal hemisphere of glaucomatous eyes.

PMID- 24290802
TI  - Diagnostic utility of adipophilin immunostain in periocular carcinomas.
AB  - PURPOSE: To determine the efficacy of adipophilin immunohistochemistry in the
      diagnosis of sebaceous carcinoma of the ocular adnexal region and to provide the
      guidelines for interpretation of this immunostain. DESIGN: Retrospective,
      histopathologic case series. PARTICIPANTS: A total of 25 patients with sebaceous
      carcinoma, 21 patients with basal cell carcinoma, 22 patients with conjunctival
      squamous cell carcinoma, 9 patients with cutaneous squamous cell carcinoma, and 5
      patients with conjunctival mucoepidermoid carcinoma. METHODS: Immunohistochemical
      staining for adipophilin was performed on paraffin-embedded tissues and
      correlated with hematoxylin-eosin, periodic acid-Schiff (PAS), and mucicarmine
      stained preparations. Immunostaining was quantified by light microscopy and with
      a computerized image analysis system of scanned images. Statistical analysis was
      performed to compare immunostaining patterns within the tumor categories by stage
      and grade, between the different neoplasms, and for correlation between light
      microscopy observations and computerized image analysis. MAIN OUTCOME MEASURES:
      Localization of adipophilin immunostain, intensity of immunostaining, percent of
      immunoreactive cells, percentages of vacuolar staining and granular staining, and
      vacuole size. RESULTS: Adipophilin expression was observed in 100% of sebaceous
      carcinomas, 100% of cutaneous squamous cell carcinomas, 95% of basal cell
      carcinomas, 73% of conjunctival squamous cell carcinomas, and 60% of
      mucoepidermoid carcinomas. Sebaceous carcinomas demonstrated significantly
      stronger adipophilin expression, a greater number of intracytoplasmic vacuoles,
      and larger vacuoles. The specificity and sensitivity of adipophilin
      immunostaining in the diagnosis of sebaceous carcinoma were both 100% when more
      than 5% of the staining occurred in vacuoles (<95% granular staining). The
      diagnostic sensitivity and specificity were 100% and 96%, respectively, when the
      staining was graded as moderately or strongly intense and were 92% and 85% when
      the vacuoles were greater than 1.5 MUm in diameter. CONCLUSIONS: Although
      upregulation of neoplastic steatogenesis is observed in both sebaceous and
      nonsebaceous carcinomas, the pattern and intensity of adipophilin immunostaining
      are helpful in distinguishing sebaceous carcinoma from other neoplasms with
      overlapping histology.

PMID- 24290804
TI  - Abnormal deep retinal capillary networking and microaneurysms in the outer
      nuclear layer of diabetic eyes.

PMID- 24290803
TI  - Genetic susceptibility, dietary antioxidants, and long-term incidence of age
      related macular degeneration in two populations.
AB  - OBJECTIVE: To examine effect modification between genetic susceptibility to age
      related macular degeneration (AMD) and dietary antioxidant or fish consumption on
      AMD risk. DESIGN: Pooled data analysis of population-based cohorts. PARTICIPANTS:
      Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).
      METHODS: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], beta-carotene,
      and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were
      estimated from food frequency questionnaires. The AMD genetic risk was classified
      according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924)
      as low (no or 1 risk allele) or high (>= 2 risk alleles). Interactions between
      dietary intake and genetic risk levels were assessed. Associations between
      dietary intake and AMD risk were assessed comparing the highest with the 2 lower
      intake tertiles by genetic risk subgroups using discrete logistic regression,
      conducted in each study separately and then using pooled data. Participants
      without AMD lesions at any visit were controls. We adjusted for age and sex in
      analyses of each cohort sample and for smoking status and study site in pooled
      data analyses. MAIN OUTCOME MEASURES: All 15-year incident late AMD cases were
      confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS.
      Intergrader reproducibility was assessed in an early AMD subsample, with 86.4%
      agreement between BMES and RS graders, allowing for a 1-step difference on a 5
      step AMD severity scale. RESULTS: In pooled data analyses, we found significant
      interaction between AMD genetic risk status and LZ intake (P=0.0009) but
      nonsignificant interactions between genetic risk status and weekly fish
      consumption (P=0.05) for risk of any AMD. Among participants with high genetic
      risk, the highest intake tertile of LZ was associated with a >20% reduced risk of
      early AMD, and weekly consumption of fish was associated with a 40% reduced risk
      of late AMD. No similar association was evident among participants with low
      genetic risk. No interaction was detected between beta-carotene or vitamin C and
      genetic risk status. CONCLUSIONS: Protection against AMD from greater LZ and fish
      consumption in persons with high genetic risk based on 2 major AMD genes raises
      the possibility of personalized preventive interventions.

PMID- 24290805
TI  - Driving habits in older patients with central vision loss.
AB  - OBJECTIVE: To determine if central visual loss is associated with driving
      cessation, driving restriction, or other-driver preference. DESIGN: Cross
      sectional study. PARTICIPANTS: Sixty-four subjects with bilateral visual loss
      (<20/32 in better eye) or severe unilateral visual loss (<20/200) from age
      related macular degeneration (AMD) and 58 normally sighted controls between 60
      and 80 years of age. METHODS: Participants self-reported driving habits. Other
      driver preference was defined as preferring that another drive when there is more
      than 1 driver in the car. Subjects reporting 2 or more driving limitations were
      considered to have restricted their driving. MAIN OUTCOME MEASURES: Self-reported
      driving cessation, other-driver preference, and driving restriction. RESULTS: Age
      related macular degeneration subjects were older (74.7 vs. 69.7 years), had worse
      visual acuity (VA; mean better-eye VA, 0.43 vs. 0.08 logarithm of minimum angle
      of resolution [logMAR]) and contrast sensitivity (CS; 1.4 vs. 1.9 log units of CS
      [logCS]), and were more likely to be white when compared with controls (P<0.001
      for all). Drivers with AMD-related vision loss were more likely to avoid driving
      over longer distances, beyond 1 hour, at night, and in unfamiliar conditions (P <
      0.05 for all). In multivariate models, driving cessation was associated with
      worse better-eye VA (odds ratio [OR], 1.5 per 1-line decrement in VA; P<0.001)
      and worse binocular CS (OR, 1.36 per 0.1 logCS increment; P = 0.005); however,
      AMD group status was not associated with driving cessation (OR, 1.9; P = 0.35).
      Factors predicting driving restriction were AMD (OR, 9.0; P = 0.004), worse
      vision (OR, 2.5 per line of VA loss; P<0.001), lower CS (OR, 2.2 per 0.1-logCS
      increment; P<0.001), and female gender (OR, 27.9; P = 0.002). Other-driver
      preference was more common with worse vision (OR, 1.6 per 0.1-logMAR increment; P
      = 0.003), female gender (OR, 4.5; P = 0.02), and being married (OR, 3.8; P =
      0.04). CONCLUSIONS: Most patients with AMD-related central vision loss continue
      to drive, but demonstrate significant driving restrictions, especially with more
      severe VA and CS loss. Future work should determine which driving adaptations the
      visually impaired best balance safety and independence.

PMID- 24290806
TI  - Defining 10-2 visual field progression criteria: exploratory and confirmatory
      factor analysis using pointwise linear regression.
AB  - PURPOSE: To test different visual field progression criteria using trend analysis
      in a glaucoma population followed with long sequences of 10-2 tests as a first
      attempt to understand and document rates of progression in the central field.
      DESIGN: Retrospective cohort study. PARTICIPANTS: We included 146 eyes of 146
      patients with established glaucoma. METHODS: Pointwise linear regression analysis
      using the methods of ordinary least squares was performed on the 68 test
      locations of the 10-2 visual field sequences. Threshold sensitivities at each
      test location were plotted as the dependent variable against follow-up time as
      the independent variable. Statistically significant progression or improvement of
      a visual field test point was defined if its regression slope measured <=-1.0
      dB/year or >=+1.0 dB/year, respectively, at P<0.01. We explored sets of criteria
      to define visual field progression, generating a hypothetical sensitivity
      (progression), specificity (improvement), and progression-to-improvement ratio
      (PIR) for each criterion. The criterion with the highest PIR was deemed the one
      with best performance. Latent class analysis (LCA) was used to determine visual
      field sectors with highest inter-correlation. MAIN OUTCOME MEASURES: The
      performance of different visual field progression criteria to detect fast rates
      of mean deviation (MD) change. RESULTS: Median baseline 10-2 MD value was -12.0
      dB (interquartile range [IQR], -6.7 to -17.8 dB), and the median rate of 10-2 MD
      change over time was -0.38 dB/year (IQR, -0.07 to -0.77 dB/year). The highest PIR
      was obtained with the progression criterion requiring at least 3 test points
      located in the same LCA-derived 10-2 visual field sector progressing faster than 
      1.0 dB/year at P<0.01. This criterion was further validated for content and
      convergence. CONCLUSIONS: This is the first study to investigate progression
      criteria for 10-2 visual fields using rates of change and to test their
      performance and validity. These findings may be useful to improve the monitoring
      of patients with glaucoma at different levels of functional loss and to develop
      new perimetric algorithms that scrutinize specific visual field locations for a
      more accurate detection of progression.

PMID- 24290808
TI  - Choice of labeling and cell line influences interactions between the Fab fragment
      AbD15179 and its target antigen CD44v6.
AB  - Medical imaging by use of immunotargeting generally relies on a labeled molecule
      binding to a specific target on the cell surface. It is important to utilize both
      cell-based and time-resolved binding assays in order to understand the properties
      of such molecular interactions in a relevant setting. In this report we describe
      the detailed characterization of the interaction properties for AbD15179, a
      promising CD44v6-targeting antibody fragment for radio-immunotargeting. Influence
      of labeling and cell-line model on the protein interaction kinetics was assessed
      using three different labeling approaches ((111)In, (125)I and FITC) on three
      different squamous carcinoma cell lines. Interactions were measured using time
      resolved assays on living cells, and further analyzed with Interaction Map(r).
      Results demonstrated a general biphasic appearance of a high- and a low-affinity
      binding event in all cases. The relative contribution from these two interactions
      differed between conjugates. For (125)I-Fab, the population of low-affinity
      binders could be significantly increased by extending the chloramine T exposure
      during labeling, whereas the (111)In-labeling predominantly resulted in a high
      affinity interaction. Interactions were also shown to be cell line dependent,
      with e.g. SCC-25 cells generally mediating a faster dissociation of conjugates
      compared to the other cell lines. In conclusion, we report both cell line
      dependent and labeling associated variations in interaction kinetics for AbD15179
      binding to CD44v6. This has implications for cell-based kinetic assays and
      applications based on labeled conjugates in general, as well as in a clinical
      setting, where each individual tumor may create different kinetic profiles for
      the same conjugate. 

PMID- 24290807
TI  - Ribonucleotides as nucleotide excision repair substrates.
AB  - The incorporation of ribonucleotides in DNA has attracted considerable notice in
      recent years, since the pool of ribonucleotides can exceed that of the
      deoxyribonucleotides by at least 10-20-fold, and single ribonucleotide
      incorporation by DNA polymerases appears to be a common event. Moreover
      ribonucleotides are potentially mutagenic and lead to genome instability. As a
      consequence, errantly incorporated ribonucleotides are rapidly repaired in a
      process dependent upon RNase H enzymes. On the other hand, global genomic
      nucleotide excision repair (NER) in prokaryotes and eukaryotes removes damage
      caused by covalent modifications that typically distort and destabilize DNA
      through the production of lesions derived from bulky chemical carcinogens, such
      as polycyclic aromatic hydrocarbon metabolites, or via crosslinking. However, a
      recent study challenges this lesion-recognition paradigm. The work of Vaisman et
      al. (2013) [34] reveals that even a single ribonucleotide embedded in a
      deoxyribonucleotide duplex is recognized by the bacterial NER machinery in vitro.
      In their report, the authors show that spontaneous mutagenesis promoted by a
      steric-gate pol V mutant increases in uvrA, uvrB, or uvrC strains lacking rnhB
      (encoding RNase HII) and to a greater extent in an NER-deficient strain lacking
      both RNase HI and RNase HII. Using purified UvrA, UvrB, and UvrC proteins in in
      vitro assays they show that despite causing little distortion, a single
      ribonucleotide embedded in a DNA duplex is recognized and doubly-incised by the
      NER complex. We present the hypothesis to explain the recognition and/or
      verification of this small lesion, that the critical 2'-OH of the ribonucleotide 
      with its unique electrostatic and hydrogen bonding properties - may act as a
      signal through interactions with amino acid residues of the prokaryotic NER
      complex that are not possible with DNA. Such a mechanism might also be relevant
      if it were demonstrated that the eukaryotic NER machinery likewise incises an
      embedded ribonucleotide in DNA. 

PMID- 24290809
TI  - Photopatternable and photoactive hydrogel for on-demand generation of hydrogen
      peroxide in cell culture.
AB  - Oxidative stress, largely mediated by reactive oxygen species (ROS), is a nearly
      ubiquitous component in complex biological processes such as aging and disease.
      Optimal in vitro methods used in elucidating disease mechanisms would deliver of
      low levels of hydrogen peroxide, emulating the in vivo pathological state, but
      current methods are limited by kinetic stability or accurate measurement of the
      dose administered. Here we present an in vitro platform that exploits
      anthraquinone catalysts for the photocatalytic production of hydrogen peroxide.
      This system can be dynamically tuned to provide constant generation of hydrogen
      peroxide at a desired physiologic rate over at least 14 days and is described
      using a kinetic model. Material characterization and stability is discussed along
      with a proof-of-concept in vitro study that assessed the viability of cells as
      they were oxidatively challenged over 24 h at different ROS generation rates.

PMID- 24290810
TI  - Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin
      expression in a mouse model of muscular dystrophy.
AB  - Skeletal muscle is a highly organized tissue in which the extracellular matrix
      (ECM) is composed of highly-aligned cables of collagen with nanoscale feature
      sizes, and provides structural and functional support to muscle fibers. As such,
      the transplantation of disorganized tissues or the direct injection of cells into
      muscles for regenerative therapy often results in suboptimal functional
      improvement due to a failure to integrate with native tissue properly. Here, we
      present a simple method in which biodegradable, biomimetic substrates with
      precisely controlled nanotopography were fabricated using solvent-assisted
      capillary force lithography (CFL) and were able to induce the proper development
      and differentiation of primary mononucleated cells to form mature muscle patches.
      Cells cultured on these nanopatterned substrates were highly-aligned and
      elongated, and formed more mature myotubes as evidenced by up-regulated
      expression of the myogenic regulatory factors Myf5, MyoD and myogenin (MyoG).
      When transplanted into mdx mice models for Duchenne muscular dystrophy (DMD), the
      proposed muscle patches led to the formation of a significantly greater number of
      dystrophin-positive muscle fibers, indicating that dystrophin replacement and
      myogenesis is achievable in vivo with this approach. These results demonstrate
      the feasibility of utilizing biomimetic substrates not only as platforms for
      studying the influences of the ECM on skeletal muscle function and maturation,
      but also to create transplantable muscle cell patches for the treatment of
      chronic and acute muscle diseases or injuries. 

PMID- 24290811
TI  - Neutral biodegradable lipid-envelope-type nanoparticle using vitamin A-Scaffold
      for nuclear targeting of plasmid DNA.
AB  - Biomembranes and cytoplasm, a diffusion-limited region for nanoparticles are
      critical barriers to be overcome for the successful gene delivery. We herein
      report on a neutral, and intracellularly degradable lipid nanoparticle (LNP),
      containing encapsulated plasmid DNA (pDNA) that can be effectively delivered to
      the nucleus. A key material component in this particle is a vitamin A-scaffold SS
      cleavable Proton-Activated Lipid-like Material ((SS)PalmA), which contains
      tertiary amine groups as proton sponge units that can respond to the acidic pH in
      endosomes, disulfide bonding for programmed collapse in the cytoplasm, and
      retinoic acid (RA) as a hydrophobic unit for assembly into LNP. LNP prepared
      using (SS)PalmA (LNP(PalmA)) exhibited a 15-fold higher gene expression activity
      compared to particles prepared with a simple acyl chain (myristoyl group)
      scaffold one (LNPPalmM). Intracellular imaging studies revealed that LNP(PalmA)
      unexpectedly showed excessive endosome-disruptive characteristics. Furthermore,
      the decapsulation of pDNA slowly, but successively occurred in parallel with peri
      nuclear accumulation. Nuclear targeting was blocked in the presence of native RA.
      Collectively, LNP(PalmA) is an intelligent particle that passes through the
      cytoplasm in particle form with the aid of the intrinsic nuclear transport system
      of RA, and thereafter releases its encapsulated pDNA for effective gene
      expression.

PMID- 24290812
TI  - Elucidating the molecular mechanism for the intracellular trafficking and fate of
      block copolymer micelles and their components.
AB  - Block copolymer micelles have shown promise for the intracellular delivery of
      chemotherapeutic agents, proteins, and nucleic acids. Understanding the mechanism
      of their intracellular trafficking and fate, including the extracellular efflux
      of the polymers, will help improve their efficacy and minimize their safety
      risks. In this Leading Opinion paper, we discuss the molecular mechanism of block
      copolymer micelle trafficking, from intracellular uptake to extracellular efflux,
      on the basis of studies with HeLa cells. By using FRET (fluorescence resonance
      energy transfer) with confocal microscopy, we found that, following their
      intracellular transport via endocytosis, the micelles dissociated into their
      polymeric components in late endosomes and/or lysosomes. Furthermore, we
      confirmed that the intrinsic proteins NPC1 and ORP2 are involved in the
      intermembrane transfer of polymers from the endosome to the plasma membrane via
      the ER (endoplasmic reticulum) by using knockdown experiments with siRNAs. After
      the polymers were transported to the plasma membrane with the aid of ORP2, they
      were extruded into the cell medium via ABC transporter, ABCB1. Experiments with
      ABCB1-expressing vesicles indicated that the polymer itself, and not the
      fluorescent compounds, was recognized by the transporter. These findings, and the
      analysis of related mechanisms, provide valuable information that should help
      minimize the potential risks associated with the intracellular accumulation of
      block copolymer micelles and to improve their therapeutic efficacy. 

PMID- 24290813
TI  - The role of the orphan G protein-coupled receptor 37 (GPR37) in multiple myeloma
      cells.
AB  - The orphan G protein-coupled receptor 37 (GPR37) is homologous to endothelin (ETB
      R) and bombesin (GRP-R, NMB-R) receptors. The present study was undertaken to
      determine the expression and functional significance of GPR37 in human multiple
      myeloma (MM). We found that GPR37 was lowly expressed in MM cell adhesion model
      and highly expressed in proliferating cells. In vitro, meddling with the
      expression of GPR37 affected the CAM-DR by regulating the ability of cell
      adhesion and the activity of Akt and ERK in MM cells. Further studies indicated
      the positive role of GPR37 in the proliferation of MM cells. 

PMID- 24290814
TI  - Movement assessment battery for children-2: translation, reliability, and
      validity for Brazilian children.
AB  - The Movement Assessment Battery for Children 2nd edition (MABC-2) is a well
      recognized assessment used to identify children with Developmental Coordination
      Disorder (DCD). Although researchers and practitioners across Brazil have used
      the MABC-2 to identify children with motor deficits, its validation for this
      particular population has yet to be investigated. In this study, we translated
      all MABC-2 items and validated them with respect to content, construct and
      criteria validity. The validation process involved 13 experts in Motor
      Development and a total of 844 children (3-13 years old) from two different
      states in Brazil. A cross-cultural translation method yielded a Brazilian
      Portuguese version of the battery. The expert panel confirmed language clarity
      and pertinence of the items. High intra- and inter-rater reliability and internal
      consistency for the MABC-2 was established for Brazilian children. A discriminant
      analysis confirmed the MABC-2 power (.80) to differentiate children with DCD and
      those at risk for DCD from typically developing children. Predictive validity was
      observed for the impairment scores and a percentile main effect was found in the
      repeated measures ANOVA (ICC: .93 and .73, respectively). Although our data are
      not representative of the entire country, this study is the first to confirm that
      the original standardized scores established for the MABC-2 are valid in
      Brazilian children. 

PMID- 24290815
TI  - Assessing the yield, microstructure, and texture properties of miniature
      Chihuahua-type cheese manufactured with a phospholipase A1 and exopolysaccharide
      producing bacteria.
AB  - Chihuahua cheese or Mennonite cheese is one of the most popular and consumed
      cheeses in Mexico and by the Hispanic community in the United States. According
      to local producers the yield of Chihuahua cheese ranges from 9 to 9.5 kg of
      cheese from 100 kg of milk. Cheese yield is a crucial determinant of
      profitability in cheese-manufacturing plants; therefore, different methods have
      been developed to increase it. In this work, a miniature Chihuahua-type cheese
      model was used to assess the effect of a phospholipase A1 (PL-A1) and
      exopolysaccharide (EPS)-producing bacteria (separately and in combination) on the
      yield, microstructure, and texture of cheese. Four different cheeses were
      manufactured: cheese made with PL-A1, cheese made with EPS-producing bacteria,
      cheese with both PL-A1 and EPS-producing bacteria, and a cheese control without
      PL-A1 or EPS-producing bacteria. The compositional analysis of cheese was carried
      out using methods of AOAC International (Washington, DC). The actual yield and
      moisture-adjusted yield were calculated for all cheese treatments. Texture
      profile analyses of cheeses were performed using a texture analyzer. Micrographs
      were obtained by electron scanning microscopy. Fifty panelists carried out
      sensorial analysis using ranking tests. Incorporation of EPS-producing bacteria
      in the manufacture of cheese increased the moisture content and water activity.
      In contrast, the addition of PL-A1 did not increase fat retention or cheese
      yield. The use of EPS alone improved the cheese yield by increasing water and fat
      retention, but also caused a negative effect on the texture and flavor of
      Chihuahua cheese. The use of EPS-producing bacteria in combination with PL-A1
      improved the cheese yield and increased the moisture and fat content. The cheeses
      with the best flavor and texture were those manufactured with PL-A1 and the
      cheeses manufactured with the combination of PL-A1 and EPS-producing culture.

PMID- 24290816
TI  - Comparison of peripartum metabolic status and postpartum health of Holstein and
      Montbeliarde-sired crossbred dairy cows.
AB  - Objectives of the current experiment were to evaluate plasma concentrations of
      metabolites and haptoglobin peripartum, uterine health and involution, and
      follicle growth and resumption of cyclicity of Holstein (HO) and Montbeliarde
      sired crossbred cows. Cows (52 HO and 52 crossbred) were enrolled in the study 45
      d before expected calving date. Cows had body weight and body condition score
      recorded on d -45, -14, 0, 1, 28, and 56 relative to calving. Dry matter intake
      was calculated for a subgroup of cows (25 HO and 38 crossbred) from 6 wk before
      to 6 wk after calving. Blood was sampled weekly from d -14 to 56 relative to
      calving for determination of glucose, nonesterified fatty acid, and beta
      hydroxybutyrate concentrations; from d -7 to 21 relative to calving for
      determination of haptoglobin concentration; and from d 14 to 56 postpartum for
      determination of progesterone concentration. Cows were examined at calving and on
      d 4, 7, 10, and 14 postpartum for diagnosis of postparturient diseases, on d 24
      postpartum for diagnosis of purulent vaginal discharge, and on d 42 postpartum
      for diagnosis of subclinical endometritis. Uteri and ovaries were examined by
      ultrasonography every 3 d from d 14 to 41 postpartum. Milk yield and composition
      were measured monthly and yield of milk, fat, protein, and energy-corrected milk
      were recorded for the first 90 d postpartum. Body weight was not different
      between Holstein and crossbred cows, but HO cows had reduced body condition score
      compared with crossbred cows. Even though DMI from 6 wk before to 6 wk after
      calving tended to be greater for HO cows (16.8 +/- 0.7 vs. 15.3 +/- 0.5 kg/d), HO
      cows tended to have more pronounced decline in dry matter intake, expressed in
      percentage of body weight from d -15 to 0 relative to calving. Energy-corrected
      milk and nonesterified fatty acid and beta-hydroxybutyrate concentrations were
      not different between breeds. No differences were observed in incidence of
      retained fetal membranes, metritis, and subclinical endometritis, but HO cows
      tended to be more likely to have pyrexia from d 0 to 15 postpartum (50.0 vs.
      31.4%) and to have greater incidence of purulent vaginal discharge (44.2 vs.
      26.5%) than crossbred cows. Holstein cows were more likely to have at least 1
      uterine disorder postpartum than crossbred cows (63.5 vs. 36.7%). No differences
      between breeds were observed in uterine involution. Holstein cows had larger
      subordinate follicles (10.1 +/- 0.4 vs. 8.9 +/- 0.5) and a greater number of
      class III follicles (1.6 +/- 0.1 vs. 1.2 +/- 0.1) than crossbred cows.
      Furthermore, the first corpus luteum postpartum of HO cows was diagnosed at a
      slower rate compared with crossbred cows. Crossbred cows had improved uterine
      health compared with HO cows and this may have been a consequence of heterosis
      and (or) breed complementarity and less pronounced decrease in DMI during the
      last days of gestation.

PMID- 24290817
TI  - Short communication: Effects of analgesic use postcalving on cow welfare and
      production.
AB  - The aim of this study was to assess the welfare and production of cows given an
      analgesic drug (carprofen, 1.4 mg/kg i.v.) within 6h after calving. The study was
      performed in a dairy farm with approximately 1,000 milking cows. Behavior,
      clinical indices, and production data (milk yield and fertility) of cows treated
      with carprofen (n = 19) or a placebo (n = 20) were compared. Additionally,
      differences related to parity (primiparous vs. multiparous) were analyzed. No
      significant differences were observed in the time of placental expulsion or
      incidence of clinical disease over the 3 d postpartum, but more animals from the
      analgesia group were observed eating during the first hours after calving.For
      unassisted calvings, the rectal temperature 24h postpartum was lower in the cows
      given analgesic. Total lactation yields at 305 d in milk were higher in the
      primiparous cows treated with carprofen. Fewer cows were pregnant at 220 d
      postpartum in the treated group as the use of carprofen increased the time from
      calving to conception. This study suggests that pain management after parturition
      leads to earlier feed intake after calving and that this may lead to higher milk
      yield in first-lactation animals.

PMID- 24290818
TI  - Milk production and composition of mid-lactation cows consuming perennial
      ryegrass-and chicory-based diets.
AB  - Dry matter intakes (DMI), nutrient selection, and milk production responses of
      dairy cows grazing 3 herbage-based diets offered at 2 allowances were measured.
      The 2 allowances were 20 (low) and 30 (high) kg of dry matter (DM)/cow per day
      and these were applied to 3 herbage types: perennial ryegrass (PRG) and chicory
      (CHIC+) monocultures and a mixed sward of chicory and perennial ryegrass (MIX).
      The CHIC+ diet was supplemented with alfalfa hay (approximately 2 kg of DM/cow
      per day) to maintain dietary neutral detergent fiber (NDF) concentration and all
      diets were supplemented with energy-based pellets (6 kg of DM/cow per day).
      Holstein-Friesian dairy cows averaging 136 +/- 30 d in milk were allocated to 4
      replicates of the 6 treatments using stratified randomization procedures. Cows
      were adapted to their experimental diets over a 14-d period, with measurements of
      DMI, milk yield, and composition conducted over the following 10 d. Herbage DMI
      was lowest (12.8 vs. 14.0 kg of DM/d) for CHIC+ compared with the MIX and PRG,
      although total forage intake (grazed herbage plus hay) was similar (14.0 to 15.0
      kg of DM/d) across the 3 treatments. Milk production, milk protein, and milk fat
      concentrations were not different between herbage types. Grazed herbage DMI
      increased with increasing herbage allowance and this was associated with
      increased milk protein concentration (3.23 to 3.34%) and total casein production
      (41.7 to 43.6 mg/g). Concentrations of polyunsaturated fatty acids in milk fat,
      particularly linoleic acid, were increased in milk from cows offered the CHIC+ or
      the MIX diets, indicating potential benefits of chicory herbage on milk fatty
      acid concentrations. Although feeding CHIC+ or MIX did not increase milk yield,
      these herbage types could be used as an alternative to perennial ryegrass pasture
      in spring.

PMID- 24290819
TI  - Short communication: Genetic parameters of individual fatty acids in milk of
      Canadian Holsteins.
AB  - The objective of the present study was to estimate heritabilities of milk fatty
      acids (FA) and genetic and phenotypic correlations among milk FA and milk
      production traits in Canadian Holsteins. One morning milk sample was collected
      from each of 3,185 dairy cows between February and June 2010 from 52 commercial
      herds enrolled in Valacta (Ste-Anne-de-Bellevue, Quebec, Canada). Individual FA
      percentages (g/100 g of total FA) were determined for each sample by gas
      chromatography. After editing the data, 2,573 cows from 46 herds remained.
      Genetic parameters were estimated using multitrait animal models fitted under
      REML. The model included fixed effects of age at calving and stage of lactation
      each nested within parity and random effects of herd-year-season of calving,
      animal, and residual. The pedigree of animals with data was traced back 5
      generations on both the male and female sides to account for relationships among
      animals. The estimates of heritability for individual FA ranged from 0.01 to
      0.39, with standard errors ranging from 0.01 to 0.06. Generally, monounsaturated
      FA (MUFA) and saturated FA (SFA) showed higher heritability estimates than
      polyunsaturated FA (PUFA). Overall, SFA were negatively genetically correlated
      with MUFA and PUFA, whereas genetic correlations between MUFA and PUFA were
      positive. The SFA showed positive associations with fat yield and fat percentage,
      whereas unsaturated FA were negatively associated with fat yield and fat
      percentage. Bovine milk FA composition could be improved through genetic
      selection, and selection for MUFA or against SFA could alter the bovine milk fat
      profile in a desirable direction. 

PMID- 24290820
TI  - Prediction of insemination outcomes in Holstein dairy cattle using alternative
      machine learning algorithms.
AB  - When making the decision about whether or not to breed a given cow, knowledge
      about the expected outcome would have an economic impact on profitability of the
      breeding program and net income of the farm. The outcome of each breeding can be
      affected by many management and physiological features that vary between farms
      and interact with each other. Hence, the ability of machine learning algorithms
      to accommodate complex relationships in the data and missing values for
      explanatory variables makes these algorithms well suited for investigation of
      reproduction performance in dairy cattle. The objective of this study was to
      develop a user-friendly and intuitive on-farm tool to help farmers make
      reproduction management decisions. Several different machine learning algorithms
      were applied to predict the insemination outcomes of individual cows based on
      phenotypic and genotypic data. Data from 26 dairy farms in the Alta Genetics
      (Watertown, WI) Advantage Progeny Testing Program were used, representing a 10-yr
      period from 2000 to 2010. Health, reproduction, and production data were
      extracted from on-farm dairy management software, and estimated breeding values
      were downloaded from the US Department of Agriculture Agricultural Research
      Service Animal Improvement Programs Laboratory (Beltsville, MD) database. The
      edited data set consisted of 129,245 breeding records from primiparous Holstein
      cows and 195,128 breeding records from multiparous Holstein cows. Each data point
      in the final data set included 23 and 25 explanatory variables and 1 binary
      outcome for of 0.756 +/- 0.005 and 0.736 +/- 0.005 for primiparous and
      multiparous cows, respectively. The naive Bayes algorithm, Bayesian network, and
      decision tree algorithms showed somewhat poorer classification performance. An
      information-based variable selection procedure identified herd average conception
      rate, incidence of ketosis, number of previous (failed) inseminations, days in
      milk at breeding, and mastitis as the most effective explanatory variables in
      predicting pregnancy outcome.

PMID- 24290821
TI  - Exploring the value of routinely collected herd data for estimating dairy cattle
      welfare.
AB  - Routine on-farm assessment of dairy cattle welfare is time consuming and,
      therefore, expensive. A promising strategy to assess dairy cattle welfare more
      efficiently is to estimate the level of animal welfare based on herd data
      available in national databases. Our aim was to explore the value of routine herd
      data (RHD) for estimating dairy cattle welfare at the herd level. From November
      2009 through March 2010, 7 trained observers collected data for 41 welfare
      indicators in a selected sample of 183 loose-housed and 13 tethered Dutch dairy
      herds (herd size: 10 to 211 cows) using the Welfare Quality protocol for cattle.
      For the same herds, RHD relating to identification and registration, management,
      milk production and composition, and fertility were extracted from several
      national databases. The RHD were used as potential predictors for each welfare
      indicator in logistic regression at the herd level. Nineteen welfare indicators
      were excluded from the predictions, because they showed a prevalence below 5% (15
      indicators), or were already listed as RHD (4 indicators). Predictions were less
      accurate for 7 welfare indicators, moderately accurate for 14 indicators, and
      highly accurate for 1 indicator. By forcing to detect almost all herds with a
      welfare problem (sensitivity of at least 97.5%), specificity ranged from 0 to
      81%. By forcing almost no herds to be incorrectly classified as having a welfare
      problem (specificity of at least 97.5%), sensitivity ranged from 0 to 67%.
      Overall, the best-performing prediction models were those for the indicators
      access to at least 2 drinkers (resource based), percentage of very lean cows,
      cows lying outside the supposed lying area, and cows with vulvar discharge
      (animal based). The most frequently included predictors in final models were
      percentages of on-farm mortality in different lactation stages. It was concluded
      that, for most welfare indicators, RHD have value for estimating dairy cattle
      welfare. The RHD can serve as a prescreening tool for detecting herds with a
      welfare problem, but this should be followed by a verification of the level of
      welfare in an on-farm assessment to identify false-positive herds. Consequently,
      the number of farm visits needed for routine welfare assessments can be reduced.
      The RHD also hold value for continuous monitoring of dairy cattle welfare.
      Prediction models developed in this study, however, should first be validated in
      additional field studies. 

PMID- 24290822
TI  - Optimizing production of in vivo-matured oocytes from superstimulated Holstein
      cows for in vitro production of embryos using X-sorted sperm.
AB  - The present study aimed to establish an efficient system for the production of
      female embryos from dairy cows by in vitro fertilization (IVF) using X-sorted
      sperm and in vivo-matured oocytes collected by ovum pick up (OPU). Nonlactating
      Holstein cows (n = 36) were administered a controlled intravaginal progesterone
      releasing (controlled internal drug release) device (d 0), underwent dominant
      follicle ablation (DFA) or ovulation by administration of 100 MUg of GnRH on d 5,
      and were superstimulated with FSH and PGF2alpha, following standard procedures.
      Controlled internal drug release devices were removed on the evening of d 8 or on
      the morning of d 9, depending on the experiment. For LH surge induction, 200 MUg
      of GnRH was administered on the morning of d 10 (0 h). In experiment 1, the peak
      (48.1%) of ovulating follicles was detected at 29 to 32 h after GnRH injection (0
      h), and the range in the timing of the initiation of ovulation was less by timing
      from GnRH administration (30.0 +/- 2.8h) rather than by timing the onset of
      estrus (32.7 +/- 4.7h). Only 0.9% of total ovulated follicles were recorded
      before 26 h after GnRH injection. Therefore, OPU was carried out at 26 h and IVF
      occurred at 30 h after GnRH in experiments 2 and 3. In experiment 2, 83.3 +/-
      10.8% of oocytes with expanded cumulus cells had extruded the first polar body at
      30 h after GnRH injection. The aim of experiment 3 was to compare the effect of
      either DFA or GnRH-induced LH surge before superstimulation on the efficiency of
      embryo production by IVF following superstimulation. Progesterone concentrations
      from d 10 to 12 in the DFA group were lower than those in the GnRH group. A
      greater proportion of recovered oocytes with expanded cumulus cells from >= 8-mm
      follicles was observed in the DFA group than in the GnRH group (95.9 and 77.4%,
      respectively). Blastocyst rates in the DFA and GnRH groups (58.0 and 52.8%,
      respectively) did not differ from those of oocytes collected from nonstimulated
      OPU and matured in vitro (49.9%). However, the proportion of high-quality
      blastocysts was higher in the DFA group compared with the GnRH group (54.9 vs.
      21.5%). Our results demonstrate that high rates of good-quality blastocysts can
      be produced by IVF with X-sorted frozen sperm using in vivo-matured oocytes
      collected by OPU from cows after DFA and superstimulation combined with ovulation
      induction.

PMID- 24290823
TI  - Risk-based audit selection of dairy farms.
AB  - Dairy farms are audited in the Netherlands on numerous process standards. Each
      farm is audited once every 2 years. Increasing demands for cost-effectiveness in
      farm audits can be met by introducing risk-based principles. This implies
      targeting subpopulations with a higher risk of poor process standards. To select
      farms for an audit that present higher risks, a statistical analysis was
      conducted to test the relationship between the outcome of farm audits and bulk
      milk laboratory results before the audit. The analysis comprised 28,358 farm
      audits and all conducted laboratory tests of bulk milk samples 12 mo before the
      audit. The overall outcome of each farm audit was classified as approved or
      rejected. Laboratory results included somatic cell count (SCC), total bacterial
      count (TBC), antimicrobial drug residues (ADR), level of butyric acid spores
      (BAB), freezing point depression (FPD), level of free fatty acids (FFA), and
      cleanliness of the milk (CLN). The bulk milk laboratory results were
      significantly related to audit outcomes. Rejected audits are likely to occur on
      dairy farms with higher mean levels of SCC, TBC, ADR, and BAB. Moreover, in a
      multivariable model, maxima for TBC, SCC, and FPD as well as standard deviations
      for TBC and FPD are risk factors for negative audit outcomes. The efficiency
      curve of a risk-based selection approach, on the basis of the derived regression
      results, dominated the current random selection approach. To capture 25, 50, or
      75% of the population with poor process standards (i.e., audit outcome of
      rejected), respectively, only 8, 20, or 47% of the population had to be sampled
      based on a risk-based selection approach. Milk quality information can thus be
      used to preselect high-risk farms to be audited more frequently.

PMID- 24290824
TI  - Invited review: Microbial evolution in raw-milk, long-ripened cheeses produced
      using undefined natural whey starters.
AB  - The robustness of the starter culture during cheese fermentation is enhanced by
      the presence of a rich consortium of microbes. Natural starters are consortia of
      microbes undoubtedly richer than selected starters. Among natural starters,
      natural whey starters (NWS) are the most common cultures currently used to
      produce different varieties of cheeses. Undefined NWS are typically used for
      Italian cooked, long-ripened, extra-hard, raw milk cheeses, such as Parmigiano
      Reggiano and Grana Padano. Together with raw milk microbiota, NWS are responsible
      for most cheese characteristics. The microbial ecology of these 2 cheese
      varieties is based on a complex interaction among starter lactic acid bacteria
      (SLAB) and nonstarter lactic acid bacteria (NSLAB), which are characterized by
      their different abilities to grow in a changing substrate. This review aims to
      summarize the latest findings on Parmigiano Reggiano and Grana Padano to better
      understand the dynamics of SLAB, which mainly arise from NWS, and NSLAB, which
      mainly arise from raw milk, and their possible role in determining the
      characteristics of these cheeses. The review is presented in 4 main sections. The
      first summarizes the main microbiological and chemical properties of the ripened
      cheese as determined by cheese-making process variables, as these variables may
      affect microbial growth. The second describes the microbiota of raw milk as
      affected by specific milk treatments, from milking to the filling of the cheese
      milk vat. The third describes the microbiota of NWS, and the fourth reviews the
      knowledge available on microbial dynamics from curd to ripened cheese. As the
      dynamics and functionality of complex undefined NWS is one of the most important
      areas of focus in current food microbiology research, this review may serve as a
      good starting point for implementing future studies on microbial diversity and
      functionality of undefined cheese starter cultures. 

PMID- 24290825
TI  - Short communication: Genetic characterization of antimicrobial resistance in
      Acinetobacter isolates recovered from bulk tank milk.
AB  - A total of 176 Acinetobacter isolates, including 57 Acinetobacter baumannii
      originally obtained from 2,287 bulk tank milk (BTM) samples in Korea was
      investigated for the genetic basis of antimicrobial resistance using molecular
      methods. In addition, the occurrence and cassette content of integrons were
      examined and the genetic diversity of A. baumannii strains identified was
      evaluated. Aminoglycoside-modifying enzyme genes were detected in 15 (88.2%) of
      the 17 aminoglycoside-resistant Acinetobacter isolates tested. The most common
      aminoglycoside-modifying enzyme gene identified was adenylyltransferase gene aadB
      (n = 9), followed by phosphotransferase genes aphA6 (n = 7) and aphA1 (n = 5). Of
      the 31 isolates resistant to tetracycline, tet(39) was detected in 20 of them.
      The genetic basis of resistance to sulfonamide was identified in 15 (53.6%) of 28
      trimethoprim-sulfamethoxazole-resistant isolates and 9 (32.1%) of them carried
      both sul1 and sul2 genes. A blaADC-7-like gene was detected in 1 beta-lactam
      resistant A. baumannii. Furthermore, class 1 integron was identified in 11
      Acinetobacter isolates. Two gene cassettes dfrA15, conferring resistance to
      trimethoprim, and aadA2, conferring resistance to aminoglycosides, were
      identified in 8 Acinetobacter isolates. None of the isolates was positive for
      class 2 or class 3 integrons. Pulsed-field gel electrophoresis revealed that most
      of the A. baumannii strains from BTM samples were genetically diverse, indicating
      that the occurrence of A. baumannii strains in BTM was not the result of
      dissemination of a single clone. Elucidation of resistance mechanisms associated
      with the resistance phenotype and a better understanding of resistance genes may
      help in the development of strategies to control infections, such as mastitis,
      and to prevent further dissemination of antibiotic resistance genes. To the best
      of our knowledge, this is the first report of molecular characterization of
      antimicrobial-resistant Acinetobacter spp. from milk.

PMID- 24290826
TI  - Consultancy to dairy farmers relating to animal health and herd health management
      on small- and medium-sized farms.
AB  - The objectives of this study were to obtain information about animal health
      challenges for dairy farmers of small- and medium-sized herds and about the
      fields in which consultancy services should be improved. The hyperlink to an
      internet-based survey was sent to 9,021 farmers in Austria. The survey included
      questions about the participants and their farms, about who is consulting with
      the farmers with regard to animal health, feeding, sire selection, construction
      of barns and animal husbandry, about animal health issues farmers find most
      challenging, and about their demands for improved consultancy services. The
      questionnaire was completed anonymously. Analyses were stratified by milk yield
      (categorized) and whether farmers worked full-time or part-time. The overall
      response rate was 11.3% (n=1,018). The majority of farms kept less than 20 cows
      (54.0%) or 20 to 50 cows (40.1%). With regard to animal health, the veterinarian
      was the most important consultant for the majority of farmers (84.6%). On issues
      related to feeding, sire selection, and stable construction, the veterinarian was
      seen as a less important consultant than specialists in these fields (20.4, 11.6,
      and 7.9% suggested the veterinarian as an important consultant in these areas).
      The survey indicated that reproductive disorders, udder disease, poor conception
      rate, lameness, and calf diarrhea represent the most important challenges to
      farmers. Of these, concerns about calf diarrhea were affected by milk yield of
      the herds and management. More high- than low-yielding farms (11.7 vs. 6.4%) and
      more full-time than part-time managed herds (9.6 vs.4.3%) regarded calf diarrhea
      as an important problem. Farmers would welcome improved consultancy with regard
      to fertility, feeding, and sire selection. The results indicated which animal
      health issues farmers find particularly challenging and displayed which areas
      farmers require improved consultancy services. Veterinarians and organizations
      offering consultancy should take the results into consideration in improving or
      adapting their advisory services. 

PMID- 24290827
TI  - Identification of a microscopically selected microorganism in milk samples.
AB  - Identification of unwanted microbial contaminants microscopically observed in
      food products is challenging due to their low abundance in a complex matrix,
      quite often containing other microorganisms. Therefore, a selective
      identification method was developed using laser capture microdissection in
      combination with direct-captured cell PCR. This procedure was validated with
      Geobacillus stearothermophilus and further used to identify microbial
      contaminants present in some industrial milk samples. The microscopically
      observed contaminants were identified as mainly Methylobacterium species. 

PMID- 24290828
TI  - Improved performance and heightened neutrophil responses during the neonatal and
      weaning periods among outdoor group-housed Holstein calves.
AB  - The objective was to determine if outdoor group housing of Holstein calves
      influences metabolic status, leukocyte responses, and behavior compared with
      individually housed calves. Forty-nine Holstein heifer calves (2 +/- 1 d of age)
      were randomly assigned to 1 of 2 treatments: individually housed (G1; n = 22) or
      group housed [3 calves per pen (G3); n = 27]. The space allowances per calf were
      4.8 and 7.0m(2) for G1 and G3, respectively. All calves were offered an identical
      plane of milk replacer nutrition (747 and 1,010 g of DM/d of a 28% CP:20% fat
      milk replacer from wk 1 to 2 and wk 3 to 6, respectively). Weaning was initiated
      during wk 7 by removing the p.m. feeding and calves were completely weaned when
      they consumed 900 g of calf starter/d (as fed) for 2 consecutive days after d 54.
      At d 90, calves were commingled into random outdoor groups of 5 calves per pen.
      Peripheral blood was collected during the neonatal (d 3, 10, and 21), weaning (d
      46, 48, and 54), and commingling periods (d 90, 93, and 98) and was analyzed for
      neutrophil oxidative burst (OB) capacity when cocultured with Escherichia coli,
      neutrophil surface L-selectin protein expression, and whole-blood secretion of
      tumor necrosis factor-alpha when cocultured with lipopolysaccharide. Starter
      intake was greater for G3 during the postweaning period (wk 8 to 12). Average
      daily gain was greater for G3 than G1 from d 54 to 68 and tended to be greater
      after commingling from d 113 to 133. During the neonatal period, G3 calves had
      more activated neutrophils, as evidenced by increased neutrophil L-selectin
      protein expression and a tendency for increased percentage of neutrophils
      producing an OB than G1 calves. During weaning, G3 calves continued to have more
      activated neutrophils with increased L-selectin expression on d 46 and 48 and a
      greater OB intensity throughout the period. No differences were observed among
      leukocyte responses between treatments at d 93 and 98. Outdoor group-housed
      Holstein calves had improved performance and heightened neutrophil responses
      compared with individually housed calves.

PMID- 24290829
TI  - Life-cycle assessment of bioproducts. Preface.

PMID- 24290830
TI  - Focus.

PMID- 24290831
TI  - Laryngeal cancer management in a small, rural, multidisciplinary team setting: 15
      year review.
AB  - BACKGROUND: The Cumberland Infirmary, Carlisle, serves a largely remote, rural
      population of 330 000. The aim of this study was to report the treatment and
      survival figures for patients treated for laryngeal cancer at this centre.
      METHODS: The study included 209 consecutive patients with squamous cell carcinoma
      of the larynx diagnosed between 1996 and 2010 at the Cumberland Infirmary.
      RESULTS: Disease-specific survival was 100 per cent for stage one, 76 per cent
      for stage two, 87 per cent for stage three and 46 per cent for stage four. In
      total, 76 patients (36 per cent) had a laryngectomy, either as primary treatment
      or as a salvage procedure. CONCLUSION: Our tumour-specific survival rate was very
      high, and this success may be due in part to high rates of surgical intervention.
      Survival data compared favourably with other centres, despite less radical
      radiotherapy regimes. Laryngeal cancer can be managed effectively in a small,
      relatively remote, multidisciplinary team setting.

PMID- 24290832
TI  - Device thrombosis in HeartMate II continuous-flow left ventricular assist
      devices: a multifactorial phenomenon.
AB  - BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVADs) are
      increasingly used to support patients with advanced heart failure (HF). Device
      thrombosis is a serious complication of CF-LVADs, but its precise prevalence and
      etiology remains uncertain. METHODS: Root-cause analysis was performed in all
      cases with device thrombosis confirmed upon explant among patients implanted with
      a HeartMate II (HM II) from January 1, 2009 to November 15, 2012. Cannula
      position and bend relief integrity were assessed and charts were reviewed with
      particular attention to anti-coagulation and infection profiles. RESULTS:
      Nineteen of 177 patients (11%) were found to have device thrombosis of various
      etiologies after a mean of 351 +/- 311 days, representing 0.12 event/patient
      year. Of the 5 mechanically induced thromboses, proximate etiology was severely
      abnormal inflow cannula position in 3 patients and bend relief disconnect with
      deformed outflow graft in 2 patients. One patient had a hypercoagulable disorder
      with prior arterial embolism. In the remaining 13 patients (age 61 +/- 14 years,
      77% male, 69% Caucasian), "non-mechanical" device thrombosis occurred after 357
      +/- 383 days; INR at the time of diagnosis was 1.81 (1.62 to 2.07); and mean
      device speed was 8,855 +/- 359 rpm. Five of 13 patients (38%) had an infection
      during the month leading up to device thrombosis. Of note, lactate dehydrogenase
      (LDH) was already elevated at the time of discharge in patients who would later
      develop non-mechanical device thrombosis (423 [354 to 766] vs 352 [272 to 373]
      U/liter, p < 0.01). CONCLUSIONS: Device thrombosis is a multifactorial
      phenomenon, and differentiation of mechanical and non-mechanical causes is an
      essential step for individual diagnosis and treatment plans. Larger studies
      excluding patients with obvious mechanical etiology are needed to investigate
      biologic and/or management-related risk factors for device thrombosis. Our
      findings suggest that LDH may be an early risk marker. Due to the difficulty in
      treating late-stage device thrombosis, we suggest early use of simple tests to
      rule out both causes of thrombosis, such as X-rays and closer LDH monitoring (bi
      weekly).

PMID- 24290833
TI  - Carotid-bulb thrombus and continuous-flow left ventricular assist devices: a
      novel observation.

PMID- 24290834
TI  - [Ocular manifestations in Behcet's disease].
AB  - Uveitis is the most common ocular symptom in Behcet's disease. It is considered
      as a diagnostic criterion of the disease. Anterior uveitis is always non
      granulomatous, and sometimes associated with hypopion. Posterior involvement may
      include vitritis, retinal infiltrates, sheathing of retinal veins, occlusive
      vasculitis, and macular edema. Behcet's disease is chronic, and characterized by
      a spontaneously relapsing and remitting course. Male patients with younger age at
      onset and worse visual acuity at presentation, have higher risk of visual loss
      over time. The main goals in the management of patients with Behcet's disease
      associated uveitis are rapid suppression of intraocular inflammation,
      preservation of vision, prevention of recurrences, and achievement of remission
      sustained after discontinuation of treatment. New therapeutic strategies such as
      interferon alpha and TNF alpha blockers have dramatically improved the visual
      prognosis of patients with intraocular inflammation related to this chronic and
      potentially blinding condition. 

PMID- 24290835
TI  - Multidetector-row CT of tumour-bowel fistula: Experience at a tertiary cancer
      centre.
AB  - AIM: To study the clinical and multidetector computed tomography (MDCT) features
      of tumour-bowel fistula (TBF). MATERIALS AND METHODS: Fifty-one patients (27
      women; mean age 57.4 years, range 30-77years) with TBF presenting to our
      institution between January 2005 and February 2012 were identified
      retrospectively from the radiology database. MDCT images before, at, and
      subsequent to diagnosis of TBF were reviewed by three radiologists in consensus;
      clinical presentation, management, and outcome were documented from electronic
      medical records. RESULTS: Of 51 patients, small bowel (n = 22) was the most
      common site with gastrointestinal stromal tumour (GIST) being the most common
      sarcoma subtype (n = 10). TBF was treatment-associated (TTBF) in 40 patients
      [78%; 22 of whom had received molecular targeted therapy (MTT)], and spontaneous
      (STBF) in 11 patients (22%). Thirty-one patients (61%) were symptomatic at the
      time of TBF detection. TTBF was more often asymptomatic (19/40 versus 1/11;
      Fisher's exact test p = 0.03). In the TTBF group, 16 had a partial response,
      seven had stable disease, and 17 had progressive disease. Treatment was
      discontinued or changed to an alternative regimen in 27/40 patients, and 13/40
      patients continued with the same regimen. TBF persisted in 27/33 patients (82%)
      who underwent CT follow-up. Thirty-one of the 51 patients were deceased at the
      time of analysis. Time from diagnosis of TBF to death was shorter with STBF (1.8
      months) than with TTBF (6.4 months). CONCLUSION: TBF is often associated with MTT
      and can be seen with treatment response or progression. TTBF is more frequently
      asymptomatic. TBF is usually managed conservatively by discontinuing treatment,
      but often persists on CT follow-up.

PMID- 24290836
TI  - Practical guide to measuring physical activity.

PMID- 24290838
TI  - Higher insulin and glucagon-like peptide-1 (GLP-1) levels in healthy, young South
      Asians as compared to Caucasians during an oral glucose tolerance test.
AB  - OBJECTIVE: Higher insulin levels during an oral glucose test (OGTT) have been
      shown in South Asians. We aimed to investigate if this increased insulin response
      causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide
      1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in
      this ethnic group. METHODS: A prolonged, 6-h, 75-g OGTT was performed in healthy,
      young Caucasian (n=10) and South Asian (n=8) men. The glucose, insulin and GLP-1
      response was measured and indices of insulin sensitivity and beta-cell activity
      were calculated. RESULTS: Age (Caucasians (CAU) 21.5+/-0.7 years vs South Asians
      (SA) 21.4+/-0.7 years (mean+/-SEM)) and body mass index (CAU 22.7+/-0.7 kg/m(2)
      vs SA 22.1+/-0.8 kg/m(2)) were comparable between the two groups. South Asian men
      were more insulin resistant, as indicated by a comparable glucose but
      significantly higher insulin response, and a significantly lower Matsuda index
      (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1
      response, as reflected by a higher area under the curve for GLP-1 (CAU 851+/-99.8
      mmol/l vs SA 1235+/-155.0 mmol/L). During the whole 6-h period, no reactive
      hypoglycemia was observed. CONCLUSION: Healthy, young South Asian men have higher
      insulin levels during an OGTT as compared to Caucasians. This does not, however,
      lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased
      levels of GLP-1. Whether this is an adaptive response to facilitate
      hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant
      state has yet to be elucidated.

PMID- 24290837
TI  - An examination of sex and racial/ethnic differences in the metabolic syndrome
      among adults: a confirmatory factor analysis and a resulting continuous severity
      score.
AB  - OBJECTIVE: The metabolic syndrome (MetS) is typically diagnosed based on
      abnormalities in specific clustered clinical measures that are associated with
      increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus
      (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our
      goals were to use confirmatory factor analysis (CFA) to delineate differential
      contributions to MetS by sub-group, and if contributions were discovered, develop
      sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH
      DESIGN AND METHODS: Using data on adults from the National Health and Nutrition
      Examination Survey 1999-2010, we performed a CFA of a single MetS factor that
      allowed differential loadings across groups, resulting in a sex and
      race/ethnicity-specific continuous MetS severity score. RESULTS: Loadings to the
      single MetS factor differed by sub-group for each MetS component (p<0.001), with
      lower factor loadings among non-Hispanic-blacks for triglycerides and among
      Hispanics for waist circumference. Systolic blood pressure exhibited low factor
      loadings among all groups. MetS severity scores were correlated with biomarkers
      of future disease (high-sensitivity C-reactive-protein, uric acid, insulin
      resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS
      but high MetS severity scores that were not significantly different from other
      racial/ethnic groups. CONCLUSIONS: This analysis among adults uniquely
      demonstrated differences between sexes and racial/ethnic groups regarding
      contributions of traditional MetS components to an assumed single factor. The
      resulting equations provide a clinically-accessible and interpretable continuous
      measure of MetS for potential use in identifying adults at higher risk for MetS
      related diseases and following changes within individuals over time. These
      equations hold potential to be a powerful new outcome for use in MetS-focused
      research and interventions.

PMID- 24290839
TI  - Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease.

PMID- 24290840
TI  - A possible outbreak of swine influenza, 1892.
AB  - Influenza A viruses are globally enzootic in swine populations. Swine influenza
      has been recognised only since 1918, but an anecdotal report suggests that a
      swine-influenza epizootic might have occurred in England in 1892, at the same
      time as an explosive epidemic (or pandemic recurrence) of human influenza. This
      outbreak suggests that the ecobiological association between human and swine
      influenza could extend to before 1918. By contrast with the recent documentation
      of swine influenza, influenza in horses has been well documented for hundreds of
      years, and was often linked temporally and geographically to epidemics of human
      influenza. Both decreased contact between people and horses, and the concomitant
      increase in swine production over the past century, might have altered the
      character and dynamics of influenza host-switch events between people and
      domestic mammals. 

PMID- 24290841
TI  - Internet-based surveillance systems for monitoring emerging infectious diseases.
AB  - Emerging infectious diseases present a complex challenge to public health
      officials and governments; these challenges have been compounded by rapidly
      shifting patterns of human behaviour and globalisation. The increase in emerging
      infectious diseases has led to calls for new technologies and approaches for
      detection, tracking, reporting, and response. Internet-based surveillance systems
      offer a novel and developing means of monitoring conditions of public health
      concern, including emerging infectious diseases. We review studies that have
      exploited internet use and search trends to monitor two such diseases: influenza
      and dengue. Internet-based surveillance systems have good congruence with
      traditional surveillance approaches. Additionally, internet-based approaches are
      logistically and economically appealing. However, they do not have the capacity
      to replace traditional surveillance systems; they should not be viewed as an
      alternative, but rather an extension. Future research should focus on using data
      generated through internet-based surveillance and response systems to bolster the
      capacity of traditional surveillance systems for emerging infectious diseases. 

PMID- 24290842
TI  - A conjugate vaccine against typhoid fever.

PMID- 24290844
TI  - Development of a patient-specific simulation tool to analyse aortic dissections:
      assessment of mixed patient-specific flow and pressure boundary conditions.
AB  - Aortic dissection has high morbidity and mortality rates and guidelines regarding
      surgical intervention are not clearly defined. The treatment of aortic dissection
      varies with each patient and detailed knowledge of haemodynamic and mechanical
      forces would be advantageous in the process of choosing a course of treatment. In
      this study, a patient-specific dissected aorta geometry is constructed from
      computed tomography scans. Dynamic boundary conditions are implemented by
      coupling a three element Windkessel model to the 3D domain at each outlet, in
      order to capture the essential behaviour of the downstream vasculature. The
      Windkessel model parameters are defined based on clinical data. The predicted
      minimum and maximum pressures are close to those measured invasively.
      Malperfusion is indicated and complex flow patterns are observed. Pressure, flow
      and wall shear stress distributions are analysed. The methodology presented here
      provides insight into the haemodynamics in a patient-specific dissected aorta and
      represents a development towards the use of CFD simulations as a diagnostic tool
      for aortic dissection. 

PMID- 24290843
TI  - Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid
      fever in adults, children, and infants in south and southeast Asia: results from
      two randomised, observer-blind, age de-escalation, phase 2 trials.
AB  - BACKGROUND: Typhoid vaccination is a public health priority in developing
      countries where young children are greatly affected by typhoid fever. Because
      present vaccines are not recommended for children younger than 2 years, the
      Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi
      CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety
      of Vi-CRM197 in participants of various ages in endemic countries in south and
      southeast Asia. METHODS: We did two randomised, observer-blind, age de
      escalation, phase 2 trials at two sites in Pakistan and India (study A), and at
      one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012.
      Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12
      months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer
      generated randomisation list (block size of four) to receive either 5 MUg Vi
      CRM197 or 25 MUg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate
      vaccine in children younger than 2 years). Both infant populations received Vi
      CRM197 concomitantly with vaccines of the Expanded Programme on Immunization
      (EPI), according to WHO schedule. With the exception of designated study site
      personnel responsible for vaccine preparation, study investigators, those
      assessing outcomes, and data analysts were masked to treatment allocation. We
      specified no a-priori null hypothesis for the immunogenicity or safety objectives
      and all analyses were descriptive. Analyses were by modified intention-to-treat.
      These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and
      NCT01437267. FINDINGS: 320 participants were enrolled and vaccinated in the two
      trials: 200 in study A (all age groups) and 120 in study B (children and infants
      only), of whom 317 (99%) were included in the modified intention-to-treat
      analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi
      antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117-369]),
      children (201 U/mL [138-294] to 368 U/mL [234-580]), and older infants (179 U/mL
      [129-250] to 249 U/mL [130-477]). However, in children and older infants, a
      second dose of conjugate vaccine had no incremental effect on antibody titres
      and, at all ages, concentrations of antibodies increased substantially 6 months
      after vaccination (from 55 U/mL [33-94] to 63 U/mL [35-114] in adults, from 23
      U/mL [15-34] to 51 U/mL [34-76] in children, and from 21 U/mL [14-31] to 22 U/mL
      [14-33] in older infants). Immune response in infants aged 6-8 weeks was lower
      than that in older participants and, 6 months after third vaccination, antibody
      concentrations were significantly higher than pre-vaccination concentrations in
      Filipino (21 U/mL [16-28] vs 2.88 U/mL [1.95-4.25]), but not Pakistani (3.76 U/mL
      [2.77-5.08] vs 2.77 U/mL [2.1-3.66]), infants. Vi-CRM197 was safe and well
      tolerated and did not induce any significant interference with EPI vaccines. No
      deaths or vaccine-related serious adverse events were reported throughout the
      studies. INTERPRETATION: Vi-CRM197 is safe and immunogenic in endemic populations
      of all ages. Given at 9 months of age, concomitantly with measles vaccine, Vi
      CRM197 shows a promise for potential inclusion in EPI schedules of countries
      endemic for typhoid. An apparent absence of booster response and a reduction in
      antibody titres 6 months after immunisation should be further investigated, but
      data show that an immunogenic typhoid vaccine can be safely delivered to infants
      during EPI visits recommended by WHO. FUNDING: Sclavo Vaccines Association and
      Regione Toscana.

PMID- 24290845
TI  - Visual-olfactory hallucinatory synesthesia: the Charles Bonnet Syndrome with
      olfactory hallucinations.

PMID- 24290846
TI  - [A first seizure revealing Sneddon's syndrome].

PMID- 24290847
TI  - Axonal excitability in X-linked dominant Charcot Marie Tooth disease.
AB  - OBJECTIVE: We investigated peripheral nerve function in X-linked Charcot-Marie
      Tooth disease type 1 (CMTX1), and considered the functional consequences of
      mutant connexin-32. METHODS: Twelve subjects (9 female, 3 male) were assessed
      clinically, by nerve conduction and excitability studies. A model of myelinated
      axon was used to clarify the contributing changes. RESULTS: All subjects had
      abnormal nerve conduction. Excitability studies on median nerve axons showed
      greater threshold changes to hyperpolarising currents, with "fanning out" in
      threshold electrotonus, and modest changes in the recovery cycle. Modelling
      suggested shortening of internodal length, increase in nodal fast potassium
      currents, shift of the voltage activation hyperpolarisation-activated cyclic
      nucleotide-gated channels, and axonal hyperpolarisation. Plotting threshold
      versus extent of hyperpolarising threshold change in threshold electrotonus
      distinguished the CMTX1 patients from other chronic demyelinating neuropathies
      reported in the literature except hereditary neuropathy with pressure palsies
      (HNPP). CONCLUSIONS: Some measures of axonal excitability are similar in CMTX1
      and HNPP (though not the recovery cycle), but they differ from those in other
      chronic demyelinating neuropathies. The findings in CMTX1 are consistent with
      known pathology, but are not correlated to neuropathy severity. SIGNIFICANCE: The
      findings in CMTX1 could be largely the result of morphological alterations,
      rather than plasticity in channel expression or distribution.

PMID- 24290848
TI  - Neuromagnetic beta and gamma oscillations in the somatosensory cortex after music
      training in healthy older adults and a chronic stroke patient.
AB  - OBJECTIVE: Extensive rehabilitation training can lead to functional improvement
      even years after a stroke. Although neuronal plasticity is considered as a main
      origin of such ameliorations, specific subtending mechanisms need further
      investigation. Our aim was to obtain objective neuromagnetic measures sensitive
      to brain reorganizations induced by a music-supported training. METHODS: We
      applied 20-Hz vibrotactile stimuli to the index finger and the ring finger,
      recorded somatosensory steady-state responses with magnetoencephalography, and
      analyzed the cortical sources displaying oscillations synchronized with the
      external stimuli in two groups of healthy older adults before and after musical
      training or without training. In addition, we applied the same analysis for an
      anecdotic report of a single chronic stroke patient with hemiparetic arm and hand
      problems, who received music-supported therapy (MST). RESULTS: Healthy older
      adults showed significant finger separation within the primary somatotopic map.
      Beta dipole sources were more anterior located compared to gamma sources. An
      anterior shift of sources and increases in synchrony between the stimuli and beta
      and gamma oscillations were observed selectively after music training. In the
      stroke patient a normalization of somatotopic organization was observed after
      MST, with digit separation recovered after training and stimulus induced gamma
      synchrony increased. CONCLUSIONS: The proposed stimulation paradigm captures the
      integrity of primary somatosensory hand representation. Source position and
      synchronization between the stimuli and gamma activity are indices, sensitive to
      music-supported training. Responsiveness was also observed in a chronic stroke
      patient, encouraging for the music-supported therapy. Notably, changes in
      somatosensory responses were observed, even though the therapy did not involve
      specific sensory discrimination training. SIGNIFICANCE: The proposed protocol can
      be used for monitoring changes in neuronal organization during training and will
      improve the understanding of the brain mechanisms underlying rehabilitation.

PMID- 24290849
TI  - Loss of motor unit size and quadriceps strength over 10 years in post-polio
      syndrome.
AB  - OBJECTIVE: To investigate whether strength decline in post-polio syndrome (PPS)
      results from excessive distal axonal degeneration of enlarged motor units.
      METHODS: We assessed changes over 10 years in isometric quadriceps strength, mean
      motor unit action potential (MUAP) size, root mean squared (RMS) amplitude, and
      level of interference (LOI) in 47 patients with PPS and 12 healthy controls,
      using high density surface EMG. At baseline, all patients had symptomatic
      quadriceps dysfunction, evidenced by transmission defects on single-fibre EMG.
      RESULTS: MU size and strength declined significantly by 20% and 15%, respectively
      in patients with PPS. Those with the largest initial MU sizes exhibited the
      greatest losses of mean MU size (27%) and proportional decreases in quadriceps
      strength (23%). Initial strength, change in LOI and change in RMS amplitude
      together explained 35% of the variability in strength changes in patients. MU
      size of controls did not change, although they lost 29% strength. CONCLUSIONS: MU
      size and strength declined concomitantly in a homogeneous cohort of patients with
      PPS and quadriceps dysfunction. SIGNIFICANCE: This long term follow-up study
      provides evidence that size diminution of enlarged MUs combined with a reduced
      number of active MUs contributes to the gradual strength decline in PPS.

PMID- 24290850
TI  - Differing response properties of cervical and ocular vestibular evoked myogenic
      potentials evoked by air-conducted stimulation.
AB  - OBJECTIVE: To determine the amplitude changes of vestibular evoked myogenic
      potentials (VEMPs) recorded simultaneously from the neck (cVEMPs) and eyes
      (oVEMPs) in response to 500 Hz, 2 ms air-conducted sound pips over a 30 dB range.
      METHODS: Fifteen healthy volunteers (mean age 29, range 18-57 years old) and one
      patient with unilateral superior canal dehiscence (SCD) were studied. The
      stimulus was reduced in increments to 105 dB pSPL for the normals (81 dB pSPL for
      the SCD patient). A statistical criterion was used to detect responses. RESULTS:
      Ipsilateral (i-p13/n23) and contralateral (c-n12/p24/n30) peaks for the cVEMP
      montage and contralateral (c-n10/p16/n21) and ipsilateral (i-n13) peaks for the
      oVEMP montage were present for the baseline intensity. For the lowest intensity,
      6/15 subjects had responses for the i-p13 cVEMP potential and 4/15 had c-n10
      oVEMP responses. The SCD patient showed larger responses for nearly all
      intensities. The cVEMP potentials were generally well fitted by a power law
      relationship, but the oVEMP c-n10, p16 and n21 potentials showed a significant
      increase in gradient for the higher intensities. CONCLUSION: Most oVEMP and cVEMP
      responses follow a power law relationship but crossed oVEMP responses showed a
      change in gradient above a threshold. SIGNIFICANCE: The pattern of response to AC
      stimulation may be a property of the pathways underlying the potentials.

PMID- 24290851
TI  - Two-group classification of patients with obstructive sleep apnea based on
      analysis of brain recurrence.
AB  - OBJECTIVE: To demonstrate that the severity of obstructive sleep apnea (OSA)
      could be predicted algorithmically by means of recurrence analysis of the sleep
      staged electroencephalogram (EEG). METHODS: A randomly selected cohort of 20
      sleep-staged patients with OSA (apnea-hypopnea index (AHI) 5-30) was divided into
      mild and moderate sub-cohorts (AHI 5-15, 16-30, respectively), and the sleep EEG
      (C3) was analyzed using analysis of brain recurrence (ABR) (LSU cohort). Twenty
      distinct but related markers for sleep depth and fragmentation were computed from
      four ABR variables, and a marker function capable of classifying each patient
      into one of the two sub-cohorts was determined by linear discriminant analysis.
      Classification accuracy of individual patients was evaluated using area under the
      receiver operator characteristics curve (AUROC). As a control procedure, 20
      additional sleep-staged patients with OSA whose polysomnographic data was
      obtained from an independent database were also evaluated (SHHS cohort). RESULTS:
      On average, markers for sleep depth were reduced and those for sleep
      fragmentation were increased in the patients with moderate OSA, as expected. All
      patients in both cohorts were correctly classified using as few as 5-6 markers.
      SIGNIFICANCE: The degree of severity of OSA was reflected in objective changes in
      the sleep EEG. Recurrence analysis of the EEG potentially has uses beyond
      identification of the degree of OSA.

PMID- 24290852
TI  - Optimal treatment of partial thickness burns in children: a systematic review.
AB  - A large part of the patient population of a burn centre consists of children,
      most of whom are younger than four years. The majority of these young children
      suffer from superficial and deep partial thickness scald burns that may easily
      deepen to full thickness burns. A proper wound therapy, that prevents infection
      and ensures a moist wound condition, might prevent the deterioration of the
      wound. Therefore, we performed a systematic review of wound management and
      dressing materials to select the best treatment option for children with burns. A
      search in Medline and Embase revealed 51 articles for a critical appraisal. The
      articles were divided into randomized controlled trials, cohort studies and a
      group of case-reports. Total appraisal did not differ much amongst the groups;
      the level of evidence was highest in the randomized controlled trials and lowest
      in the case-reports. In 16 out of 34 comparative studies, silver sulfadiazine or
      a silver sulfadiazine/chlorhexidine-gluconate combination was the standard of
      wound care treatment. The competitor dressing was Biobrane((r)) in six studies
      and amnion membrane in three. Tulle gauze, or tulle gauze impregnated with an
      antibacterial addition were the standard of care treatment in seven studies. In
      general, membranous dressings like Biobrane((r)) and amnion membrane performed
      better than the standard of care on epithelialization rate, length of hospital
      stay and pain for treatment of partial thickness burns in children. However,
      hardly any of the studies investigated long-term results like scar formation. 

PMID- 24290853
TI  - Assessment of the health status in Brazilian burn victims five to seven months
      after hospital discharge.
AB  - PURPOSE: To evaluate health status, impact of event, anxiety, and depression in
      burn victims at five-to-seven months after hospital discharge, and to explore the
      association between those variables with age, body surface area burn (BSA), sex,
      and marital status. METHODS: Cross-sectional study involving 73 adults who were
      interviewed for general health status (BSHS-R), impact of event (IES), and
      anxiety and depression (HADS). RESULTS: Participants were mostly men (68.5%),
      with mean age 38.4 years (SD = 14.5), and mean hospital length of stay (LOS) 24.5
      days (SD = 25.3). Mean scores were: 128.1 (SD = 18.9) for BSHS-R, 62.1(SD = 35.8)
      for IES, 5.5 (SD = 4.1) for anxiety, and 3.9 (SD = 3.9) for depression. Health
      status was highly and inversely correlated with impact of event, depression,
      anxiety, LOS, number of surgeries, and BSA. Men and women differed in the BSHS-R
      affect and body image domains, and depression. Individuals with larger BSA
      reported worse scores for BSHS-R (work domain). CONCLUSION: Burn victims reported
      good health status on average, which was negatively correlated with reported
      depression, anxiety, impact of event, LOS, number of operations, and BSA. These
      findings suggest that general health might be improved by interventions that
      target modifiable behavioral factors, such as support groups and cognitive
      behavioral therapies.

PMID- 24290854
TI  - Geospatial and epidemiological analysis of severe burns in New South Wales by
      residential postcodes.
AB  - BACKGROUND: Burns are a common trauma, affecting 1% of the Australian population
      annually and are associated with significant physical, psychological, social and
      economic burdens for victims and their families. There has been a recent paradigm
      shift from the treatment of burns to a more preventative approach. OBJECTIVES: To
      examine the risk of severe burns by geographic region in New South Wales (NSW),
      Australia, using geospatial analytic techniques. METHOD: Retrospective analyses
      were carried out to examine the 2006-2010 NSW burns data collected by the NSW
      Severe Burns Injury Service. Spatial analysis software was used to map the
      relative risk of burns by postcode areas. Spatial cluster analyses were then
      undertaken for the Greater Sydney Area (GSA) using Global Moran's I statistics
      and Getis-Ord analyses. High- and low-risk populations and areas were examined to
      ascertain differences by sociodemographic characteristics, etiology and the
      extent of burn. RESULTS: Scalds were the most common types of burns and men were
      at greater risk of burns than women. There was significant clustering of burns by
      postcode area, with a higher relative risk of severe burns seen in Western Sydney
      area and lower risk observed in Eastern and Southern Sydney. In high-risk areas
      burns occurred more frequently in the 13-24 months and the 20-29 years age
      groups, while in low-risk areas burns mostly affect the 20-29 and 30-39 years age
      groups. High-risk areas were characterized by socioeconomic disadvantage.
      IMPLICATIONS: Mapping the risk of burns is a valuable tool for policy makers to
      plan and deliver targeted intervention strategies for burns prevention.

PMID- 24290855
TI  - Multiple Marjolin's ulcers arising from irradiated post-burn hypertrophic scars:
      a case report.
AB  - Marjolin's ulcer is an aggressive ulcerating cutaneous malignancy that may arise
      in chronically inflamed or traumatized skin. Frequently overlooked, this rare
      condition is classically associated with burn scars, with the process of
      malignant degeneration typically occurring over two to three decades. The most
      common histopathological pattern is squamous cell carcinoma; however, compared to
      typical squamous cell carcinomas, Marjolin's ulcers have an increased rate of
      metastasis. The correlation between radiotherapy for benign hypertrophic scarring
      and carcinogenesis is controversial, with few reports in the literature. We
      present a unique case of a 61 year old Caucasian male who was burned by scald at
      age 4, received radiotherapy for his post-burn hypertrophic scars, and later
      developed multiple Marjolin's ulcers on his left arm, chest, and right temporal
      scalp. 

PMID- 24290857
TI  - Burn and 'stick-on' ECG electrode: modified use of conventional technique.

PMID- 24290856
TI  - A rat model of full thickness thermal injury characterized by thermal
      hyperalgesia, mechanical allodynia, pronociceptive peptide release and tramadol
      analgesia.
AB  - Opioid-related side effects are problematic for burn patients. Dual mechanism
      therapeutics targeting opioid and non-opioid mechanisms may have reduced side
      effects with similar analgesic efficacy. Tramadol combines mu opioid receptor
      agonism with norepinephrine reuptake inhibition and has been effective in
      treating some types of pain. The effectiveness of tramadol in treating pain
      associated with burns is unclear. We hypothesized that tramadol is effective in
      reducing thermal injury-evoked pain behaviors in a rat model. Rats were
      anesthetized and a 100 degrees C metal probe was placed on the hindpaw for 30 s
      to induce a full thickness thermal injury. A subset of rats was perfusion fixed
      and hindpaw tissue and spinal cord collected for anatomical analysis. Rats
      received morphine (5 mg/kg; i.p.), tramadol (10-30 mg/kg; i.p.) or vehicle and
      latency to paw withdrawal from a noxious thermal or non-noxious mechanical
      stimulus was recorded every 10 min over 70 min and again at 2 h. We report that
      pain behaviors developed within 48 h and peaked at 1 week; paralleled by enhanced
      expression of pronociceptive neuropeptides in the spinal cord. Morphine and
      tramadol significantly attenuated hyperalgesia and allodynia, while not
      significantly altering motor coordination/sedation. These data indicate dual
      mechanism therapeutics may be effective for treating pain associated with burns.

PMID- 24290858
TI  - Three-dimensional digitalized virtual planning for retrograde sural neurovascular
      island flaps: a comparative study.
AB  - BACKGROUND: The purpose of this study was to explore the effectiveness and safety
      of three-dimensional (3D) digitalized planning for the sural neurovascular island
      flap in repair of soft tissue defects in the ankle and foot. METHODS: This study
      included 40 patients with soft tissue defects of the ankle and foot who underwent
      soft tissue reconstruction between October 2008 and June 2012. The patients were
      randomly assigned into two groups: 3D-reconstruction group (Group A, n=20) and
      control group (Group B, n=20). Three-dimensional, digitalized virtual planning
      was performed in the patients in Group A, who underwent computed topographic
      angiography. The survival rate, operation time, and surgical accuracy were
      compared between the two groups. RESULTS: All flaps in Group A survived and the
      recipient site primarily healed, but 4 flaps in Group B had marginal necrosis
      after the operation. During the 6-12 month follow-up period, all flaps in Group A
      had good skin quality. In Group B, hard scarring and mild contracture occurred in
      4 cases, and the patients experienced pain when walking. The survival rate of the
      flap in Group A (100%) was significantly higher than in Group B (70%). The
      operation time in Group A was significantly less than in Group B. The surgical
      accuracy in Group A was significantly better than in Group B. CONCLUSION: The
      preoperative use of 3D digitalized virtual planning for the sural neurovascular
      island flap improves the surgical accuracy, decreases the operation time, and
      increases the survival rate of the flap. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic III.

PMID- 24290859
TI  - An endovascular treatment of a thoracic aortic injury caused by a misplaced
      pedicle screw: Case report and review of the literature.
AB  - Aortic injuries are devastating complications after spinal surgery. We here would
      like to share our experience with a successful endovascular treatment of an
      iatrogenic thoracic aortic injury caused by misplaced pedicle screw after spinal
      surgery. A patient underwent posterior spinal surgery for L1 burst fracture was
      transferred to our department for instrumentation removal. An iatrogenic thoracic
      aortic injury at T11 level caused by a pedicle screw was recognized after routine
      CT scans. Complete screw extraction and instrumentation removal were performed
      after the placement of a thoracic aortic stent graft covering the injured region.
      The patient had an uneventful postoperative period and no complications were
      observed in the 1 and 12-month follow-up by contrast-enhanced CT scans. For the
      delayed thoracic aortic injuries which usually were usually shown on CT scans as
      pseudoaneurysm or penetration of the aorta, stent graft implantation would
      provide a preferred solution with high-effectiveness, low-invasiveness and fewer
      complications compared with conventional open surgery. 

PMID- 24290860
TI  - Silence is golden: an uncommon case of vocalization-triggered atrial tachycardia.
AB  - Vocalization-related atrial tachyarrhythmias are extremely rare. We describe the
      case of a young woman in whom speaking was proven to be the trigger of a nearly
      incessant right atrial tachycardia, poorly controlled with medical therapy and
      successfully treated with catheter ablation. The identification of the trigger
      was pivotal for mapping and ablation, providing a reliable means to assess the
      success of the procedure. 

PMID- 24290861
TI  - The math of sisyphus: the conundrum of stem cell administration for myocardial
      infarction and myocardial failure.

PMID- 24290862
TI  - Spontaneous chest wall hematoma with dual antiplatelet therapy.
AB  - Spontaneous chest wall hematoma is rare and has been associated with neoplasms
      and arteriovenous malformations. However, the increasing use of anticoagulant and
      antiplatelet agents has increased the clinical presentation of spontaneous
      hematomas. Clopidrogel and aspirin are antiplatelet agents widely used in the
      treatment of peripheral vascular, cerebrovascular, and coronary artery disease.
      Although bleeding is a known adverse effect, only a small number of cases of
      hematomas associated with antiplatelet agents have been described. We report a
      case of a large spontaneous latissimus dorsi hematoma in a patient receiving
      clopidogrel and aspirin therapy. 

PMID- 24290863
TI  - Reply to letter from Nair et al.--anatomical considerations for cardiac
      resynchronization therapy in transposition of the great arteries.

PMID- 24290864
TI  - Feasibility of transvenous coronary sinus lead implantation in congenitally
      corrected transposition of the great arteries.

PMID- 24290865
TI  - The impact of a breast cancer diagnosis in young women on their relationship with
      their mothers.
AB  - BACKGROUND: For young women with breast cancer mothers might either be a source
      of support or of increased stress, depending on the premorbid relationship and on
      the psychological effect of the daughter's diagnosis on her mother. OBJECTIVES:
      To examine the effects of a breast cancer diagnosis on young women's
      relationships with their mothers and the possible support needs of these mothers
      from the daughters' perspective. PATIENTS AND METHODS: We developed and pre
      tested a self-administered questionnaire on 10 survivors of breast cancer
      diagnosed <= age 40. Then, consecutive recurrence-free young women diagnosed with
      breast cancer were asked to complete the modified questionnaire. RESULTS: Of 110
      daughters approached from July/11 to May/12, 90 (82%) participated. In 11 cases
      (13%), the daughters had turned to their mothers before approaching anyone else.
      Of the 83 daughters who disclosed their diagnosis to their mothers, 76 (92%)
      stated their mothers had been emotionally and/or practically supportive, and 43
      (54%) reported that the breast cancer diagnosis had a favorable impact on their
      relationship with their mothers. Of the 35 employed mothers, 26 had taken time
      off from work to support their daughters. Nineteen mothers, eight of whom had
      been living in a different country, had slept over or moved in with daughters
      during their treatment. Twenty-two daughters believed their mothers felt
      responsible to some extent for their developing breast cancer. Fifty-nine
      daughters indicated that health care professionals could help mothers by
      providing information pamphlets, education sessions, and linking to support
      groups. CONCLUSION: Mothers are an important source of support for young
      daughters with breast cancer, with the mother-daughter relationship frequently
      becoming closer after the diagnosis. However, the practical and emotional burden
      on mothers appears to be high. Future studies should address the effects of a
      breast cancer diagnosis in young daughters from the mothers' perspective, and the
      benefit of formal supports for these mothers.

PMID- 24290866
TI  - Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as
      diagnostic and prognostic marker in neonatal sepsis.
AB  - OBJECTIVE: Triggering receptor expressed on myeloid cells-1 (TREM-1) is an
      important receptor involved in the innate inflammatory response and sepsis. We
      assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and
      49 culture-negative) and 40 healthy controls as a potential early diagnostic and
      prognostic marker for neonatal sepsis (NS). METHODS: Studied neonates were
      evaluated for early- or late-onset sepsis using clinical and laboratory
      indicators upon admission. sTREM-1 was measured on initial sepsis evaluation and
      at 48h after antibiotic therapy. For ethical reasons, cord blood samples were
      collected from control neonates and only samples from neonates that proved to be
      healthy by clinical examination and laboratory analysis were further analyzed for
      sTREM-1. RESULTS: Baseline sTREM-1 levels were significantly elevated in culture
      proven (1461.1+/-523pg/mL) and culture-negative sepsis (1194+/-485pg/mL) compared
      to controls (162.2+/-61pg/mL) with no significant difference between both septic
      groups. Culture-positive or negative septic preterm neonates had significantly
      higher sTREM-1 compared to full term neonates. sTREM-1 was significantly higher
      in neonates with early sepsis than late sepsis and was associated with high
      mortality. sTREM-1 was significantly decreased 48h after antibiotic therapy
      compared to baseline or levels in neonates with persistently positive cultures.
      sTREM-1 was positively correlated to white blood cells (WBCs), absolute
      neutrophil count, immature/total neutrophil (I/T) ratio, C-reactive protein (hs
      CRP) and sepsis score while negatively correlated to gestational age and weight.
      hs-CRP and sepsis score were independently related to sTREM-1 in multiregression
      analysis. sTREM-1 cutoff value of 310pg/mL could be diagnostic for NS with 100%
      sensitivity and specificity (AUC, 1.0 and 95% confidence interval [CI], 0.696
      1.015) while the cutoff value 1100pg/mL was predictive of survival with 100%
      sensitivity and 97% specificity (AUC, 0.978 and 95% CI, 0.853-1.13). However, hs
      CRP cutoff 13.5mg/L could be diagnostic for NS with a sensitivity of 76% and
      specificity of 72% (AUC, 0.762 and 95% CI, 0.612-0.925) and levels were not
      related to survival as no significant difference was found between dead and alive
      septic neonates. CONCLUSIONS: Elevated sTREM-1 could be considered an early
      marker for NS that reflects sepsis severity and poor prognosis.

PMID- 24290867
TI  - Perpetration patterns and environmental contexts of IPV in Sweden: relationships
      with adult mental health.
AB  - Although excellent data exist on the overall prevalence of childhood exposure to
      intimate partner violence (IPV), there is less information available on the
      specific patterns of IPV exposure in childhood and how they influence adult
      mental health. The current study examines 703 Swedish adults who reported
      exposure to IPV in childhood. Participants were part of a large national study on
      violence exposure. They provided an extensive history of their exposure to IPV
      and maltreatment experiences during childhood via electronically administered
      questionnaires. Mean comparison and multivariate regression methods were employed
      to assess differences in violence severity by reported perpetration pattern
      (mother-only, father-only, bidirectional or other), the association between
      violence severity and environmental context, and the contribution of these
      characteristics to adult mental health outcomes. Overall, violence perpetrated in
      public and by fathers was more severe and was related to poorer mental health
      outcomes in adulthood for child witnesses. These findings provide important
      insight into possible clinical "flags" for identifying children at high risk for
      exposure to IPV and abuse in the home. 

PMID- 24290868
TI  - Impact of cesarean section on placental transfusion and iron-related
      hematological indices in term neonates: a systematic review and meta-analysis.
AB  - Evidence suggests that cesarean section is likely associated with a reduced
      placental transfusion and poor hematological status in neonates. However,
      clinical studies have reported somewhat inconsistent results. We conducted a
      systematic review and meta-analysis to examine whether cesarean section affects
      placental transfusion and iron-related hematological indices. Pubmed, Web of
      Science, ScienceDirect, and Ovid Databases were searched for relevant studies
      published before April 9, 2013. Mean differences between cesarean section and
      vaginal delivery in outcomes of interests (placental residual blood volume;
      hematocrit level, hemoglobin concentration, and erythrocyte count in
      cord/peripheral blood) were extracted and pooled using a random effects model. We
      identified 15 studies (n = 8477) eligible for the meta-analysis. Compared with
      neonates born vaginally, those born by cesarean section had a higher placental
      residual blood volume [weighted mean difference (WMD), 8.87 ml; 95% confidence
      interval (CI), 2.32 ml-15.43 ml]; a lower level of hematocrit (WMD, -2.91%; 95%
      CI, -4.16% to -1.65%), hemoglobin (WMD, -0.51 g/dL; 95% CI, -0.74 g/dL to -0.27
      g/dL) and erythrocyte (WMD, -0.16 * 10(12)/L; 95% CI, -0.30 * 10(12)/L to -0.01 *
      10(12)/L). Subgroup analysis showed that the WMD for hematocrit in neonate's
      peripheral blood (-6.94%; 95% CI, -9.15% to -4.73%) was substantially lower than
      that in cord blood (-1.75%; 95% CI, -2.82%, -0.68%) (P value for testing subgroup
      differences <0.001). In conclusion, cesarean section compared with vaginal
      delivery is associated with a reduced placental transfusion and poor iron-related
      hematologic indices in both cord and peripheral blood, indicating that neonates
      delivered by cesarean section might be more likely affected by iron-deficiency
      anemia in infancy. 

PMID- 24290869
TI  - Effects of carvedilol and propranolol on circulatory regulation and oxygenation
      in cirrhosis: a randomised study.
AB  - BACKGROUND AND AIMS: Newer studies suggest that carvedilol, a beta-blocker with a
      moderate anti-alpha-1 activity, is superior to propranolol in reducing the portal
      pressure and risk of variceal bleeding. The effect on arterial blood pressure is
      a matter of concern especially in decompensated patients. AIMS: to assess
      potential differential effects of beta-blockers and beta-blockers with moderate
      anti-alpha-1 activity on selected haemodynamic, humoral, and respiratory
      characteristics in cirrhosis. METHODS: Patients with cirrhosis and portal
      hypertension were randomised to receive carvedilol (n=16) or propranolol (n=13).
      Cardiac, systemic and splanchnic parameters along with oxygen saturation and
      plasma renin were measured at inclusion and after 3 months. RESULTS: Arterial
      blood pressure, heart rate, and cardiac output decreased equally, central
      circulation time and systemic vascular resistance increased significantly but
      similarly. Central blood volume, plasma volume and arterial compliance were
      unaltered. The QTc interval and renin levels decreased in the carvedilol group,
      however not significantly different from the propranolol group. Arterial oxygen
      saturation and alveolar arterial oxygen gradient remained constant in both
      groups. Hepatic venous pressure gradient decreased equally in the carvedilol and
      propranolol groups (-17% and -20%, non significant). CONCLUSIONS: Systemic
      haemodynamics and pulmonary effects of carvedilol and propranolol are modest and
      this study could not demonstrate any significant difference between the two
      treatments.

PMID- 24290870
TI  - Immigration, European union and health issues: a commentary.

PMID- 24290871
TI  - Immunohistochemical analysis of metaplastic non-goblet columnar lined oesophagus
      shows phenotypic similarities to Barrett's oesophagus: a study in an Asian
      population.
AB  - BACKGROUND: Barrett's oesophagus is a premalignant condition, predisposing to
      oesophageal adenocarcinoma. However, some adenocarcinoma may arise in columnar
      lined oesophagus without goblet cells. Our aim was to evaluate the biological
      properties of non-goblet columnar lined oesophagus only and elucidate its
      relationship with Barrett's oesophagus and associated neoplasia. METHODS:
      Endoscopic biopsies from patients with Barrett's oesophagus (n=30), non-goblet
      columnar lined oesophagus (n=14), Barrett's oesophagus associated high grade
      dysplasia (n=6) and adenocarcinoma (n=4) were selected. Immunostaining for
      villin, claudin 3 and MUC4 was performed. Statistical analysis was performed and
      a p value <0.05 was considered significant. RESULTS: Villin and MUC4 were
      positive in 42%, 100% each and 50% in non-goblet columnar lined oesophagus,
      Barrett's oesophagus, high grade dysplasia and adenocarcinoma respectively, while
      claudin 3 was 100% positive in all the groups. In non-goblet columnar lined
      oesophagus, six cases that were villin immunopositive, showed positive expression
      for claudin 3 and/or MUC4 and there was no difference from the high grade
      dysplasia or adenocarcinoma (p>0.05). CONCLUSION: Our results indicate that a
      subset of non-goblet columnar lined oesophagus shows an intestinal phenotype
      representing an early stage of Barrett's oesophagus. This subset probably
      harbours the potential to change into adenocarcinoma in the long term.

PMID- 24290872
TI  - Epistaxis management at Guy's Hospital, 2009-2011: full audit cycles.
AB  - OBJECTIVE: To assess management of epistaxis at a tertiary ENT referral hospital
      against a recently published standard of best practice. METHODS: Fifty
      consecutive cases of acute epistaxis that required admission to Guy's Hospital in
      2009 were evaluated. Epistaxis education sessions were held to introduce our
      algorithm of best practice in tandem with an emphasis on emergency department
      care. Similar retrospective reviews were carried out in both 2010 and 2011 (on
      groups of 50 patients). RESULTS AND CONCLUSION: The first audit cycle
      demonstrated that only 8 per cent of patients underwent a suitable nasal
      examination in the emergency department prior to transfer, with no documented
      attempts at nasal cautery. Surgical intervention procedures were performed on
      only 40 per cent of eligible patients. The audit cycles that followed the
      introduction of the epistaxis algorithm demonstrated continued improvement in
      initial evaluation and management of epistaxis. In select patients,
      sphenopalatine artery ligation can provide timely, definitive management of
      refractory epistaxis.

PMID- 24290873
TI  - Developing hand therapy skills in Bangladesh: experiences of Australian
      volunteers.
AB  - INTRODUCTION: Bangladesh is a developing country whose health system is highly
      dependent on project funding from foreign countries. Interplast Australia & New
      Zealand have supported volunteer hand therapists to provide training to local
      staff in the management of hand injuries and burns since 2006. OBJECTIVES: We
      aimed to explore and describe the volunteers' own experience and provide
      recommendations for future therapy capacity building projects in developing
      countries. METHODS: This qualitative study involved nine volunteer therapists,
      who attended a focus group to discuss their experiences, including the key
      milestones, challenges, and progress achieved. The two authors analyzed
      transcripts independently and emergent themes were discussed and identified by
      consensus. RESULTS: Overall the experience was extremely positive and rewarding
      for volunteers. Key learnings and challenges encountered in this project were
      cultural differences in learning styles, the need to adapt our approach to 2
      facilitate sustainable local solutions, attrition of skilled local staff, and
      concerns regarding volunteer health and safety. Recommendations for similar
      projects include allowing adequate time for in-country scoping and planning,
      coordination and pooling of resources, and the use of strategies that encourage
      the shift to confident local ownership of ongoing learning and skill development.
      CONCLUSION: Volunteering in a health capacity building program in developing
      countries can be a challenging but immensely rewarding experience. Programs
      designed to meet the health demands in developing countries should emphasize
      adequate training of professionals in the use of transferable, sustainable and
      cost effective techniques. Time spent in the scoping and planning phase is
      crucial, as is coordination of efforts and pooling of resources. LEVEL OF
      EVIDENCE: 2C.

PMID- 24290874
TI  - Alteration of intestinal barrier function during activity-based anorexia in mice.
AB  - BACKGROUND & AIMS: Anorexia nervosa is a severe eating disorder often leading to
      malnutrition and cachexia, but its pathophysiology is still poorly defined.
      Chronic food restriction during anorexia nervosa may induce gut barrier
      dysfunction, which may contribute to disease development and its complications.
      Here we have characterized intestinal barrier function in mice with activity
      based anorexia (ABA), an animal model of anorexia nervosa. METHODS: Male C57Bl/6
      ABA or limited food access (LFA) mice were placed respectively in cages with or
      without activity wheel. After 5 days of acclimatization, both ABA and LFA mice
      had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9
      and until the end of experiment at day 17. A group of pair-fed mice (PF) was also
      compared to ABA. RESULTS: On day 17, food intake was lower in ABA than LFA mice
      (2.0 +/- 0.18 g vs. 3.0 +/- 0.14 g, p < 0.001) and weight loss was more
      pronounced in ABA and PF compared to LFA mice (23.6 +/- 1.6% and 24.7 +/- 0.7%
      vs. 16.5 +/- 1.2%; p < 0.05). Colonic histology showed decreased thickness of the
      muscularis layer in ABA compared to LFA mice (p < 0.05). Colonic permeability was
      increased in both ABA and PF compared to LFA mice (p < 0.05) but jejunal
      paracellular permeability was not affected. Expression of claudin-1 in the colon
      was lower in the ABA than the LFA group (p < 0.05), whereas occludin expression
      remained unaffected. CONCLUSION: Increased colonic permeability and histological
      alterations found in ABA mice suggest that intestinal barrier dysfunction may
      also occur in anorexia nervosa. The role of these alterations in the
      pathophysiology of anorexia nervosa should be further evaluated.

PMID- 24290875
TI  - Recognition of pharmaceutical prescriptions across the European Union: a
      comparison of five Member States' policies and practices.
AB  - BACKGROUND: In 2011, the EU Directive on Patients' Rights in Cross Border
      Healthcare was approved, including a regulation on mutual recognition of
      prescriptions. OBJECTIVE: To compare current national policies and practices on
      prescribing and dispensing, prescription-only medicines (POMs) in European
      countries in order to identify differences which could, challenge acceptance
      across borders. METHODS: Semi-structured interviews with 37 national stakeholders
      were carried out. Furthermore, data on policies for prescribing and dispensing
      POMs were gathered based on desk research, and, contacts with relevant
      authorities via a purposely designed questionnaire. RESULTS: Important
      differences exist regarding: (1) information requirements for prescriptions to
      be, legally valid, (2) generic and international non-proprietary name (INN)
      policies and (3) professionals, legally allowed to prescribe POMs. Moreover,
      there is a lack of EU-wide access to key information for, validating
      prescriptions, recognizing the equivalence of products or identifying authorised
      prescribers. CONCLUSION: Differences in legislation and its application across
      Europe pose important challenges to be, addressed by policy makers with
      appropriate actions: (1) a prescribed product may not be dispensed, to a patient
      who needs it, (2) an inappropriate product (or inappropriate instructions) could
      be, provided and (3) POMs could be dispensed and consumed or sold, based on false
      prescriptions.

PMID- 24290876
TI  - Sport participation and alcohol and illicit drug use in adolescents and young
      adults: a systematic review of longitudinal studies.
AB  - Sport participation can play an important and positive role in the health and
      development of children and youth. One area that has recently been receiving
      greater attention is the role that sport participation might play in preventing
      drug and alcohol use among youth. The current study is a systematic review of 17
      longitudinal studies examining the relationship between sport participation and
      alcohol and drug use among adolescents. Results indicated that sport
      participation is associated with alcohol use, with 82% of the included studies
      (14/17) showing a significant positive relationship. Sport participation,
      however, appears to be related to reduced illicit drug use, especially use of non
      cannabis related drugs. Eighty percent of the studies found sport participation
      associated with decreased illicit drug use, while 50% of the studies found
      negative association between sport participation and marijuana use. Further
      investigation revealed that participation in sports reduced the risk of overall
      illicit drug use, but particularly during high school; suggesting that this may
      be a critical period to reduce or prevent the use of drugs through sport. Future
      research must better understand what conditions are necessary for sport
      participation to have beneficial outcomes in terms of preventing alcohol and/or
      illicit drug use. This has been absent in the extent literature and will be
      central to intervention efforts in this area. 

PMID- 24290877
TI  - A comparison of motivations for use among users of crack cocaine and cocaine
      powder in a sample of simultaneous cocaine and alcohol users.
AB  - This study examined the motivations for using cocaine and alcohol comparing those
      who primarily smoked crack and those who primarily used cocaine powder when using
      simultaneously with alcohol. Motivations examined included: 1) to cope with a
      negative affect, 2) enhancement, 3) to be social and 4) to conform. The research
      design was a cross-sectional study in which clients in treatment for cocaine and
      alcohol problems completed a self-administered questionnaire about their
      substance use. Among those who primarily smoked crack or snorted cocaine when
      also using alcohol (n=153), there were 93 participants who reported primarily
      snorting cocaine and 60 participants who primarily reported smoking crack.
      Bivariate analyses found that those who primarily smoked crack reported lower
      social motivations to use alcohol and cocaine. When adjusting for other
      covariates in a multivariate analysis, social motivation was still significantly
      different between groups. Additionally, those who primarily smoked crack were
      more likely to be older, report higher cocaine dependence severity, be unemployed
      and were less likely to have completed some post-secondary education, than those
      who primarily snorted cocaine. No differences were found in enhancement, coping
      or conformity motivations between the two groups. These results suggest that
      simultaneous cocaine and alcohol use may have social importance to those who
      primarily snort cocaine, but that this importance is less evident to those who
      smoke crack. Consequently, future studies examining motivations for simultaneous
      cocaine and alcohol use should distinguish between different routes of cocaine
      administration. 

PMID- 24290878
TI  - Effects of resistance exercise on the HPA axis response to psychological stress
      during short-term smoking abstinence in men.
AB  - PURPOSE: The purpose of this study was to examine the effects of resistance
      exercise on the hypothalamic-pituitary-adrenal axis (HPA) response to mental
      challenge, withdrawal symptoms, urge to smoke, and cognitive stress during 24
      hour smoking abstinence. METHODS: 8 sedentary smokers (mean+/-SD age: 20.1+/
      1.7y; height: 171.6+/-10.8cm; body mass: 70.4+/-12.0kg; smoking history: 2.9+/
      0.8y) completed a 24-hour ad libitum smoking trial (SMO) followed by two 24-hour
      smoking abstinence trials. During abstinence trials, participants performed six
      whole body resistance exercises (EX) or a control condition (CON) in the morning,
      followed by mental challenge tasks in the afternoon. Plasma adrenocorticotropin
      hormone (ACTH), and salivary and serum cortisol were measured during each visit
      at rest (REST), and then before (PRE-EX), immediately after (IP-EX), and 30min
      after exercise (30-EX); and before (PRE-MC), immediately after (IP-MC), and 30min
      after mental challenge (30-MC). RESULTS: Resistance exercise significantly
      (p<=0.05) elevated plasma ACTH and serum cortisol at IP-EX during EX compared
      with SMO and CON trials. Resting ACTH, salivary and serum cortisol concentrations
      at Pre-MC did not differ between EX and CON trials. The HPA axis response to
      mental challenge was similar after EX and CON trials. Finally, resistance
      exercise did not reduce withdrawal symptoms, urge to smoke, or stress.
      CONCLUSION: Resistance exercise did not substantially alter resting HPA hormones
      or the HPA response to mental challenge tasks during 24h of smoking abstinence.

PMID- 24290879
TI  - Prevalence and correlates of smoking status among veterans affairs primary care
      patients with probable major depressive disorder.
AB  - In an attempt to guide planning and optimize outcomes for population-specific
      smoking cessation efforts, the present study examined smoking prevalence and the
      demographic, clinical and psychosocial characteristics associated with smoking
      among a sample of Veterans Affairs primary care patients with probable major
      depression. Survey data were collected between 2003 and 2004 from 761 patients
      with probable major depression who attended one of 10 geographically dispersed VA
      primary care clinics. Current smoking prevalence was 39.8%. Relative to
      nonsmokers with probable major depression, bivariate comparisons revealed that
      current smokers had higher depression severity, drank more heavily, and were more
      likely to have comorbid PTSD. Smokers with probable major depression were also
      more likely than nonsmokers with probable major depression to have missed a
      health care appointment and to have missed medication doses in the previous
      5months. Smokers were more amenable than non-smokers to depression treatment and
      diagnosis, and they reported more frequent visits to a mental health specialist
      and less social support. Alcohol abuse and low levels of social support were
      significant concurrent predictors of smoking status in controlled multivariable
      logistic regression. In conclusion, smoking prevalence was high among primary
      care patients with probable major depression, and these smokers reported a range
      of psychiatric and psychosocial characteristics with potential to complicate
      systems-level smoking cessation interventions. 

PMID- 24290881
TI  - Exploring intermolecular interactions of a substrate binding protein using a
      riboswitch-based sensor.
AB  - The study of biological transporters can be hampered by a dearth of methodology
      for tracking their activity within cells. Here, we present a means of monitoring
      the function of transport machinery within bacteria, exploiting a genetically
      encoded riboswitch-based sensor to detect the accumulation of the substrate in
      the cytoplasm. This method was used to investigate the model ABC transporter
      BtuC2D2F, which permits vitamin B12 uptake in Escherichia coli. We exploited the
      wealth of structural data available for this transporter to probe the functional
      and mechanistic importance of key residues of the substrate binding protein BtuF
      that are predicted to support its interaction with its substrate or with the BtuC
      channel-forming subunits. Our results reveal molecular interaction requirements
      for substrate binding proteins and demonstrate the utility of riboswitch-based
      sensors in the study of biological transport.

PMID- 24290880
TI  - A small-molecule inducer of PDX1 expression identified by high-throughput
      screening.
AB  - Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing
      transcription factor family, is a key transcription factor important for both
      pancreas development and mature beta cell function. The ectopic overexpression of
      Pdx1, Neurog3, and MafA in mice reprograms acinar cells to insulin-producing
      cells. We developed a quantitative PCR-based gene expression assay to screen more
      than 60,000 compounds for expression of each of these genes in the human PANC-1
      ductal carcinoma cell line. We identified BRD7552, which upregulated PDX1
      expression in both primary human islets and ductal cells, and induced epigenetic
      changes in the PDX1 promoter consistent with transcriptional activation.
      Prolonged compound treatment induced both insulin mRNA and protein and also
      enhanced insulin expression induced by the three-gene combination. These results
      provide a proof of principle for identifying small molecules that induce
      expression of transcription factors to control cellular reprogramming. 

PMID- 24290882
TI  - Deubiquitinating enzyme specificity for ubiquitin chain topology profiled by di
      ubiquitin activity probes.
AB  - Posttranslational modification with ubiquitin (Ub) controls many cellular
      processes, and aberrant ubiquitination can contribute to cancer, immunopathology,
      and neurodegeneration. The versatility arises from the ability of Ub to form
      polymer chains with eight distinct linkages via lysine side chains and the N
      terminus. In this study, we engineered Di-Ub probes mimicking all eight different
      poly-Ub linkages and profiled the deubiquitinating enzyme (DUB) selectivity for
      recognizing Di-Ub moieties in cellular extracts. Mass spectrometric profiling
      revealed that most DUBs examined have broad selectivity, whereas a subset
      displays a clear preference for recognizing noncanonical over K48/K63 Ub
      linkages. Our results expand knowledge of Ub processing enzyme functions in
      cellular contexts that currently depends largely on using recombinant enzymes and
      substrates.

PMID- 24290883
TI  - Heart rate circadian profile in the differential diagnosis between Parkinson
      disease and multiple system atrophy.
AB  - Clinical diagnostic criteria indicate presence of autonomic features as the
      primary hallmark of Multiple System Atrophy (MSA). However involvement of the
      autonomic system is also a recognized feature of Parkinson's Disease (PD),
      yielding a broad clinical overlap between the two diseases. Laboratory
      assessments may help in the differential diagnosis between PD and MSA. Ambulatory
      Monitoring of Blood Pressure (AMBP) is a suitable tool to study the circadian
      rhythm of blood pressure (BP) and heart rate (HR). Different studies reported a
      reduction of physiological BP nocturnal dipping in PD and MSA patients, but
      failed to identify a distinctive pattern discriminating the two diseases. On the
      other hand, HR nocturnal behavior has not been exhaustively analyzed. In the
      present study we compared the profiles of HR circadian rhythm in 61 PD and 19 MSA
      patients who underwent 24 h AMBP. We found higher nocturnal HR (nHR) (71.5
      beats/min +/- 7.4) in MSA compared with PD (63.8 beats/min +/- 9.6) as well as
      significantly lower nocturnal decline of HR (ndHR) in MSA (7.3% +/- 8.2) vs. PD
      (14% +/- 7.5). At a Receiver Operating Curve analysis nHR and ndHR significantly
      discriminated MSA from PD. nHR showed a sensitivity of 84.2% and a specificity of
      62.3% (AUC 0.76; 95% IC 0.65-0.85); ndHR showed a sensitivity of 68% of and a
      specificity of 77% (AUC 0.72; 95% IC 0.61-0.82). According to our findings, nHR
      is increased and ndHR is reduced in MSA compared to PD. Moreover, these two
      indices discriminate between the two diseases with acceptable accuracy.

PMID- 24290884
TI  - Quality of life: a case-controlled long-term follow-up study, comparing young
      high-functioning adults with autism spectrum disorders with adults with other
      psychiatric disorders diagnosed in childhood.
AB  - BACKGROUND: Long term outcome in childhood autism spectrum disorders (ASD) was
      evaluated by studying quality of life (QoL) in young adulthood in comparison to
      the outcome of other child psychiatric disorders. METHODS: In this follow-up
      study, objective and subjective QoL of 169 high-functioning (IQ>70) adults with
      ASD (19 to 30 years) was contrasted with QoL data of age matched adults diagnosed
      with attention deficit/hyperactivity disorder (N=85), disruptive behaviour
      disorders (N=83), and affective disorders (N=85) during childhood. The mean
      follow-up period of the ASD patients was 13.9 years. Objective QoL included
      marital status, living arrangements, level of education, employment, and usage of
      mental health care. Subjective QoL included satisfaction concerning living
      arrangements, work or education, physical condition, partner relationship, social
      relationships, state of mind, and future perspective. RESULTS: QoL was more
      compromised in adults diagnosed with ASD in childhood than in adults with other
      psychiatric disorders in childhood. A relatively large proportion of the adults
      with ASD were single, few lived with a partner or a family and many of them were
      institutionalized. Adults with ASD had lower educational levels, relatively few
      had paid employment and many were social security recipients, as compared to the
      other psychiatric patients. In case the adults with ASD used medication, 47% used
      anti-psychotics. Regarding the subjective QoL, the adults with ASD were less
      satisfied about their work or education, partner relationship, and future
      perspective than the other groups. Even when highly educated adults with ASD were
      compared to highly educated adults diagnosed with other childhood disorders, the
      QoL appeared to be more disadvantageous in adults with ASD. CONCLUSION: Many
      studies have shown that QoL is threatened in psychiatric patients, but findings
      of this study indicate that young high-functioning adults diagnosed with ASD in
      childhood are at relatively high risk for poor QoL compared to other childhood
      psychiatric disorders.

PMID- 24290885
TI  - The assessment of positive dimension of the psychosis phenotype in college
      students.
AB  - The Wisconsin Schizotypy Scales are one of the most used measuring instruments
      for the assessment of psychometric risk for psychosis. The main goal of the
      present study was to analyze the reliability of the scores and to provide new
      sources of validity evidence for the brief version of the Magical Ideation Scale
      (MIS-B) and the Perceptual Aberration Scale (PAS-B). The final sample was
      comprised of a total of 1349 university students divided into two subsamples
      (n1=710; M=19.8 years; n2=639; M=21.2 years). Results show that both measurement
      instruments have adequate psychometric properties under Classical Test Theory and
      Item Response Theory. Internal structure analysis of MIS-B and PAS-B, through
      exploratory and confirmatory factor analysis, yielded an essentially one
      dimensional solution. Cronbach's alpha coefficient for the total score of MIS-B
      ranged between 0.86 and 0.87, whereas for the PAS-B it ranged between 0.78 and
      0.89. A total of 5 items showed a differential functioning for sex. The results
      indicate that the MIS-B and PAS-B are brief measurement instruments with adequate
      psychometric properties for the assessment of the positive dimension of the
      psychosis phenotype and could be used as screening tools in the detection of
      individuals at risk for psychosis in the general population.

PMID- 24290887
TI  - Five questions on the IDF Diabetes Atlas.

PMID- 24290886
TI  - Association of stigma resistance with emotion regulation - functional magnetic
      resonance imaging and neuropsychological findings.
AB  - BACKGROUND: [corrected] Personal characteristics contribute to whether negative
      attitudes in society are internalized as deteriorating self-stigma. Studies in
      healthy subjects suggest that resilience is associated with the regulation of
      amygdala activation by the medial prefrontal cortex (mPFC), but little is known
      about the factors that contribute to individual stigma resistance in psychiatric
      patients. METHODS: We assessed stigma (by measuring association strengths between
      social inferiority and schizophrenia by an implicit association test) in 20
      patients with schizophrenia and in 16 age- and sex-matched healthy control
      subjects. The brain activation strengths were measured by functional magnetic
      resonance imaging during evaluation of schizophrenia-related statements and of
      control statements. RESULTS: Association strengths between social inferiority and
      schizophrenia were inversely related to the strength of the activation of the
      rostro-ventral mPFC. This inverse correlation survived adjustment for global
      functioning, depression symptom scores, and insight. Activation of the rostro
      ventral mPFC was negatively correlated with activation of the amygdala. The
      association strengths between social inferiority and schizophrenia correlated
      with the compromised performance in a Stroop task, which is a measure of
      cognitive regulation. DISCUSSION: Our findings suggest that individual stigma
      resistance is associated with emotion regulation. These findings may help to
      understand better stigma resistance and thereby aid the development of patient
      interventions that add to the public anti-stigma work in reducing devastating
      effects of stigma.

PMID- 24290888
TI  - Detecting adverse events in surgery: comparing events detected by the Veterans
      Health Administration Surgical Quality Improvement Program and the Patient Safety
      Indicators.
AB  - BACKGROUND: The Patient Safety Indicators (PSIs) use administrative data to
      screen for select adverse events (AEs). In this study, VA Surgical Quality
      Improvement Program (VASQIP) chart review data were used as the gold standard to
      measure the criterion validity of 5 surgical PSIs. Independent chart review was
      also used to determine reasons for PSI errors. METHODS: The sensitivity,
      specificity, and positive predictive value of PSI software version 4.1a were
      calculated among Veterans Health Administration hospitalizations (2003-2007)
      reviewed by VASQIP (n = 268,771). Nurses re-reviewed a sample of hospitalizations
      for which PSI and VASQIP AE detection disagreed. RESULTS: Sensitivities ranged
      from 31% to 68%, specificities from 99.1% to 99.8%, and positive predictive
      values from 31% to 72%. Reviewers found that coding errors accounted for some PSI
      VASQIP disagreement; some disagreement was also the result of differences in AE
      definitions. CONCLUSIONS: These results suggest that the PSIs have moderate
      criterion validity; however, some surgical PSIs detect different AEs than VASQIP.
      Future research should explore using both methods to evaluate surgical quality.

PMID- 24290890
TI  - Toxicity assessment of SiC nanofibers and nanorods against bacteria.
AB  - In the present study, evidence of the antibacterial effects of silicon carbide
      (SiC) nanofibers (NFSiC) and nanorods (NRSiC) obtained by combustion synthesis
      has been presented. It has been shown that the examined bacteria, Pseudomonas
      putida, could bind to the surface of the investigated SiC nanostructures. The
      results of respiration measurements, dehydrogenase activity measurements, and
      evaluation of viable bacteria after incubation with NFSiC and NRSiC demonstrated
      that the nanostructures of SiC affect the growth and activity of the bacteria
      examined. The direct count of bacteria stained with propidium iodide after
      incubation with SiC nanostructures revealed that the loss of cell membrane
      integrity could be one of the main effects leading to the death of the bacteria. 

PMID- 24290889
TI  - Cytogenetic endpoints and Xenobiotic gene polymorphism in lymphocytes of hospital
      workers chronically exposed to ionizing radiation in Cardiology, Radiology and
      Orthopedic Laboratories.
AB  - Ionizing radiation (IR) is known as a classical mutagen capable of inducing
      various kinds of stable and unstable chromosomal aberrations (CA) including the
      possibility of increasing the incidence of DNA damage. This study aims to assess
      occupationally induced CA in workers chronically exposed to low doses of IR in
      Radiology (RL), Cardiology (CL) and Orthopedic (OL) Laboratories in hospitals of
      Tamil Nadu. We performed the analysis of CA by trypsin G-banding, micronucleus
      (MN) assay, Comet assay and Xenobiotic-metabolizing gene polymorphisms (GSTM1,
      GSTT1 and GSTP1) in 56 exposed and 56 control subjects who were matched for
      gender and age (+/- 2 years). Higher degree of CA and MN frequencies were
      observed in exposed groups, especially in CL subjects compared to other exposed
      groups and controls (p<0.05). Higher frequency of DNA tail length and tail moment
      was observed in the CL exposed subjects compared to the RL and OL subjects. The
      frequencies of GSTM1 and GSTT1 null genotypes were 39.3 percent and 14.3 percent,
      respectively. No significant difference in allele frequencies between exposed
      subjects and controls were observed (p=0.0128). Using multiple linear regression
      analysis, statistical significance was determined for work duration and age for
      the CL, RL and OL workers and the examination of the possible impact by
      confounding factors showed few significant influences on the radiation exposure,
      as a specific biomarker. However, the findings from the present study suggest
      that, awareness should be created among the personnel exposed to radiations in
      hospital laboratories, highlighting the necessity of applying radiation
      protection principles against medical radiation exposure.

PMID- 24290891
TI  - [Ultrasound assessment of acute abdominal pain in hereditary angioedema].

PMID- 24290892
TI  - [Developmental centered care. Situation in Spanish neonatal units].
AB  - INTRODUCTION: Developmental centered care (DC) is focused on sensorineural and
      emotional development of the newborns. In Spain we have had information on the
      application of DC since 1999, but the extent of actual implementation is unknown.
      OBJETIVE: To determine the level of implementation of DC in Spanish neonatal
      units where more than 50 infants weighing under 1500g were cared for in 2012. A
      comparison was made with previous data published in 2006. MATERIAL AND METHODS: A
      descriptive observational cross-sectional study was performed using a survey with
      seven questions as in the 2006 questionnaire. RESULTS: The survey was sent to 27
      units. The response rate was 81% in 2012 versus 96% in 2006. Noise control
      measures were introduced in 73% of units in 2012 versus 11% in 2006 (P<.01). The
      use of saccharose was 50% in 2012 versus 46% in 2006 (P=.6). Parents free entry
      was 82% in 2012 versus 11% in 2006 (P<.01). Kangaroo care was used without
      restriction by 82% in 2012 compared to 31% in 2006 (P<.01). CONCLUSIONS: The
      implementation of the DC in Spain has improved. There is still room for
      improvement in areas, such as the use of saccharose or noise control. However, it
      is important to highlight the positive change that has occurred in relation to
      unrestricted parental visits.

PMID- 24290893
TI  - [Osteosarcoma of the radius after intramedullary osteosynthesis].
AB  - Osteosarcoma is a malignant neoplasm characterized by local lytic or plastic
      processes. We observed a case of radius osteosarcoma in a 10-year-old boy 3
      months after intramedullary osteosynthesis in the ipsilateral distal radius.
      Treatment consisted of amputation of the distal humerus and adjuvant
      chemotherapy; no complications were observed. 

PMID- 24290894
TI  - Sex determination using the Probabilistic Sex Diagnosis (DSP: Diagnose Sexuelle
      Probabiliste) tool in a virtual environment.
AB  - The hip bone is one of the most reliable indicators of sex in the human body due
      to the fact it is the most dimorphic bone. Probabilistic Sex Diagnosis (DSP:
      Diagnose Sexuelle Probabiliste) developed by Murail et al., in 2005, is a sex
      determination method based on a worldwide hip bone metrical database. Sex is
      determined by comparing specific measurements taken from each specimen using
      sliding callipers and computing the probability of specimens being female or
      male. In forensic science it is sometimes not possible to sex a body due to
      corpse decay or injury. Skeletalization and dissection of a body is a laborious
      process and desecrates the body. There were two aims to this study. The first aim
      was to examine the accuracy of the DSP method in comparison with a current visual
      sexing method on sex determination. A further aim was to see if it was possible
      to virtually utilise the DSP method on both the hip bone and the pelvic girdle in
      order to utilise this method for forensic sciences. For the first part of the
      study, forty-nine dry hip bones of unknown sex were obtained from the Body
      Donation Programme of the Universite Libre de Bruxelles (ULB). A comparison was
      made between DSP analysis and visual sexing on dry bone by two researchers. CT
      scans of bones were then analysed to obtain three-dimensional (3D) virtual models
      and the method of DSP was analysed virtually by importing the models into a
      customised software programme called lhpFusionBox which was developed at ULB. The
      software enables DSP distances to be measured via virtually-palpated bony
      landmarks. There was found to be 100% agreement of sex between the manual and
      virtual DSP method. The second part of the study aimed to further validate the
      method by analysing thirty-nine supplementary pelvic girdles of known sex blind.
      There was found to be a 100% accuracy rate further demonstrating that the virtual
      DSP method is robust. Statistically significant differences were found in the
      identification of sex between researchers in the visual sexing method although
      both researchers identified the same sex in all cases in the manual and virtual
      DSP methods for both the hip bones and pelvic girdles. 

PMID- 24290895
TI  - Proteomics study of silver nanoparticles toxicity on Bacillus thuringiensis.
AB  - Emerging technologies in functional genomics and proteomics provide a way of
      achieving high-throughput analyses, understanding effects on protein populations
      and sub-populations and follow up environmental stresses. To accomplish these,
      the action of homemade spherical Silver nanoparticles colloidal suspension
      (AgNPs) against Bacillus thuringiensis (isolate from Oryza sativa L. rhizosphere)
      was investigated by a proteomic approach (2-DE and NanoLC/FT-ICR MS
      identification). Thirty four responsive (up/down regulated) proteins were
      identified. Proteomic results revealed that an exposure of B. thuringiensis cells
      with different concentrations of AgNPs resulted in an accumulation of envelope
      protein precursors, indicative of the dissipation of a proton motive force.
      Identified proteins are involved in oxidative stress tolerance, metal
      detoxification, transcription and elongation processes, protein degradation,
      cytoskeleton remodeling and cell division. The expression pattern of these
      proteins and their possible involvement in the nontoxicity mechanisms were
      discussed. 

PMID- 24290896
TI  - Psychosis following chloroquine ingestion: a 10-year comparative study from a
      malaria-hyperendemic district of India.
AB  - OBJECTIVES: Serious adverse effects such as acute psychoses have been reported
      following treatment with chloroquine. Chloroquine can cause cell death, including
      neurons. We aimed to identify the most frequent type of psychiatric manifestation
      and symptomatological characteristics of psychosis following chloroquine
      ingestion (PFC). METHOD: Out of a total of 4471 randomly selected recent-onset
      psychosis patients, 3610 consecutive patients who had responded to standard
      treatment were screened for entry in the study. We compared background
      clinicodemographic profile information and psychopathology of 51 PFC patients,
      who were either drug free or drug naive, to 51 brief psychotic disorder (BPD)
      patients who were matched in terms of age, sex and education. Only those patients
      who remitted within 8 weeks (PFC patients) or 4 weeks (BPD patients) were
      included. Cranial computed tomography, electroencephalography and lumbar puncture
      of the entire experimental group were normal, and none had Mini Mental Status
      Examination score <22. Group difference and correlational statistics (parametric
      and nonparametric) have been used to test the hypotheses and explain the results.
      RESULTS: The most common (76.2%) type of psychiatric disturbance in PCF group was
      mood disorder (mixed episode) accompanied by predominant irritability with little
      blunting of affect. PFC patients characteristically had prominent positive
      symptoms with visual hallucination and derealization experiences. They were more
      restless, agitated and anxious and had more disturbed thought content and
      orientation, but better preserved insight. There was no linear relationship
      between the amount of chloroquine consumed and the severity of psychosis.
      CONCLUSION: Considering the large number of patients still receiving chloroquine
      especially in developing countries, this study has been presented to draw
      attention of the psychiatrists and other health professionals to the hazardous
      effect of chloroquine on mental health.

PMID- 24290897
TI  - Response to Donner-Banzhoff.

PMID- 24290898
TI  - DNA methylation profiles at birth and child ADHD symptoms.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a common and highly heritable
      psychiatric disorder. In addition, early life environmental factors contribute to
      the occurrence of ADHD. Recently, DNA methylation has emerged as a mechanism
      potentially mediating genetic and environmental effects. Here, we investigated
      whether newborn DNA methylation patterns of selected candidate genes involved in
      psychiatric disorders or fetal growth are associated with ADHD symptoms in
      childhood. Participants were 426 children from a large population based cohort of
      Dutch national origin. Behavioral data were obtained at age 6 years with the
      Child Behavior Checklist. For the current study, 11 regions at 7 different genes
      were selected. DNA methylation levels of cord blood DNA were measured for the 11
      regions combined and for each region separately. We examined the association
      between DNA methylation levels at different regions and ADHD symptoms with linear
      mixed models. DNA methylation levels were negatively associated with ADHD symptom
      score in the overall analysis of all 11 regions. This association was largely
      explained by associations of DRD4 and 5-HTT regions. Other candidate genes showed
      no association between DNA methylation levels and ADHD symptom score.
      Associations between DNA methylation levels and ADHD symptom score were
      attenuated by co-occurring Oppositional defiant disorder and total symptoms.
      Lower DNA methylation levels of the 7 genes assessed at birth, were associated
      with more ADHD symptoms of the child at 6 years of age. Further studies are
      needed to confirm our results and to investigate the possible underlying
      mechanism. 

PMID- 24290900
TI  - Clinical characteristics and prediction of pulmonary hypertension in severe
      emphysema.
AB  - BACKGROUND: We explored the prevalence, clinical and physiologic correlates of
      pulmonary hypertension (PH), and screening strategies in patients with severe
      emphysema evaluated for the National Emphysema Treatment Trial (NETT). METHODS:
      Patients undergoing Doppler echocardiography (DE) and right heart catheterization
      were included. Patients with mean pulmonary arterial pressure >= 25 mmHg (PH
      Group) were compared to the remainder (non-PH Group). RESULTS: Of 797 patients,
      302 (38%) had PH and 18 (2.2%) had severe PH. Compared to the non-PH Group,
      patients with PH had lower % predicted FEV1 (p < 0.001), % predicted diffusion
      capacity for carbon monoxide (p = 0.006), and resting room air PaO2 (p < 0.001).
      By multivariate analysis, elevated right ventricular systolic pressure, reduced
      resting room air PaO2, reduced post-bronchodilator % predicted FEV1, and enlarged
      pulmonary arteries on computed tomographic scan were the best predictors of PH. A
      strategy using % predicted FEV1, % predicted DLCO, PaO2, and RVSP was predictive
      of the presence of pre-capillary PH and was highly predictive of its absence.
      CONCLUSIONS: Mildly elevated pulmonary artery pressures are found in a
      significant proportion of patients with severe emphysema. However, severe PH is
      uncommon in the absence of co-morbidities. Simple non-invasive tests may be
      helpful in screening patients for pre-capillary PH in severe emphysema but none
      is reliably predictive of its presence.

PMID- 24290901
TI  - Frequency of antibodies against Besnoitia besnoiti in Brazilian cattle.
AB  - Besnoitia besnoiti is a cyst-forming parasite that has been associated with
      economic losses in Africa and Europe. Besnoitiosis is considered as a re-emergent
      disease in the European continent. It is unknown whether cattle are exposed to B.
      besnoiti in the Americas, thus the aim of this study was to serologically
      investigate antibodies against B. besnoiti in a total of 2014 cattle serum
      samples from two states from Brazil. All samples were evaluated by IFAT and part
      of the positive sera was tested by Western blot (WB) using tachyzoites extracts
      under non-reducing condition. A total of 3.48% (70/2014) of the tested sera
      reacted positively by IFAT with titers of 200 (85.7%), 400 (10%) and 800 (4.3%).
      When 47 positive samples were assessed by WB a range of antigens from 7 to 206
      kDa was recognized by the IFAT-positive sera. The results are suggestive of
      exposure of Brazilian cattle to B. besnoiti due to the titers (>= 200) observed
      for some sera using IFAT. However, the antigens recognized by the IFAT-positive
      animals did not completely match with the WB patterns previously described by
      other working groups. It is possible that Brazilian cattle are exposed to B.
      besnoiti strains with different antigenic composition of those described in the
      European and African continent. Further studies are needed to confirm the
      presence of B. besnoiti or other Besnoitia species in Brazilian cattle.

PMID- 24290899
TI  - One airway: Biomarkers of protection from upper and lower airway injury after
      World Trade Center exposure.
AB  - BACKGROUND: Firefighters exposed to World Trade Center (WTC) dust have developed
      chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1 s (FEV1).
      Overlapping but distinct immune responses may be responsible for the clinical
      manifestations of upper and lower airway injury. We investigated whether a panel
      of inflammatory cytokines, either associated or not associated with WTC-LI, can
      predict future chronic rhinosinusitis disease and its severity. METHODS: Serum
      obtained within six months of 9/11/2001 from 179 WTC exposed firefighters
      presenting for subspecialty evaluation prior to 3/2008 was assayed for 39
      cytokines. The main outcomes were medically managed CRS (N = 62) and more severe
      CRS cases requiring sinus surgery (N = 14). We tested biomarker-CRS severity
      association using ordinal logistic regression analysis. RESULTS: Increasing serum
      IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression.
      Conversely, increasing TNF-alpha increased the risk of progression. In a
      multivariable model adjusted for exposure intensity, increasing IL-6, TNF-alpha
      and neutrophil concentration remained significant predictors of progression.
      Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV1
      but in contrast to CRS, increased TNF-alpha did not increase the risk of abnormal
      FEV1. CONCLUSIONS: Our study demonstrates both independent and overlapping
      biomarker associations with upper and lower respiratory injury, and suggests that
      the innate immune response may play a protective role against CRS and abnormal
      lung function in those with WTC exposure.

PMID- 24290902
TI  - A random forest classifier for lymph diseases.
AB  - Machine learning-based classification techniques provide support for the decision
      making process in many areas of health care, including diagnosis, prognosis,
      screening, etc. Feature selection (FS) is expected to improve classification
      performance, particularly in situations characterized by the high data
      dimensionality problem caused by relatively few training examples compared to a
      large number of measured features. In this paper, a random forest classifier
      (RFC) approach is proposed to diagnose lymph diseases. Focusing on feature
      selection, the first stage of the proposed system aims at constructing diverse
      feature selection algorithms such as genetic algorithm (GA), Principal Component
      Analysis (PCA), Relief-F, Fisher, Sequential Forward Floating Search (SFFS) and
      the Sequential Backward Floating Search (SBFS) for reducing the dimension of
      lymph diseases dataset. Switching from feature selection to model construction,
      in the second stage, the obtained feature subsets are fed into the RFC for
      efficient classification. It was observed that GA-RFC achieved the highest
      classification accuracy of 92.2%. The dimension of input feature space is reduced
      from eighteen to six features by using GA. 

PMID- 24290903
TI  - [Comparison of severe neonatal acidosis rates and analysis of obstetric practices
      in two French maternities].

PMID- 24290904
TI  - Glomus jugulare tumours: a 15 year radiotherapy experience in South Australia.
AB  - Glomus jugulare tumours (GJT) are one of a family of benign hypervascular
      neoplasms that arise from chief cells of the paraganglionic tissue from the dome
      of the jugular bulb. Historically, these tumours have primarily been managed
      surgically but radiation is an alternative treatment modality. The purpose of
      this retrospective review was to determine the patient survival, tumour control,
      clinical control rates and long term toxicity of GJT treated with radiation in
      South Australia. Between 1996 and 30 June 2012, 15 patients with GJT (16 tumours)
      were managed with radiotherapy. Twelve patients were female and the median age
      was 62 years. Thirteen patients (87%) were treated with conventional external
      beam radiotherapy and two patients (13%) with stereotactic radiosurgery. The mean
      duration of follow-up was 4 years (range 1 month-15 years 4 months). The close
      out date for survival analyses was 31 October 2012. Crude overall survival,
      tumour control, clinical control and long term grade >2 toxicity rates were 100%,
      94% (15/16), 94% and 7% (1/16), respectively. The Kaplan-Meier 5 and 10 year
      clinical and tumour control rates were both 93% (95% confidence interval: 61
      99%). Radiation is an effective treatment modality for GJT. With comparable
      patient survival, arguably improved tumour and clinical control rates relative to
      surgery, minimal toxicity and ongoing advances in radiotherapy technologies,
      radiation should be strongly considered for the primary management of GJT.

PMID- 24290905
TI  - Quantitative analysis of the effect of brainstem shift on surgical approaches to
      anterolateral tumors at the craniovertebral junction.
AB  - Many anterolateral craniovertebral junction (CVJ) tumors can safely be resected
      using a simple posterolateral approach given the surgical corridor provided by
      brainstem shift. We sought to study how increasing anterolateral CVJ lesion size
      affects exposure in the posterolateral and far lateral approaches. Six cadaveric
      heads were used. A posterolateral approach was performed on one side and a far
      lateral with one-third condyle resection on the other side. Clival and brainstem
      exposure and surgical freedom were measured. A balloon catheter was used to
      simulate 10, 15, and 20mm anterolateral mass lesions. Mean clival exposure was
      significantly greater with the far lateral approach (197.4 versus [vs] 135.0
      mm(2), p=0.03) with no balloon, but this difference disappeared with lesion sizes
      of 10 mm (246.8 vs 237.9 mm(2), p=0.79), 15 mm (306.7 vs 262.4 mm(2), p=0.25),
      and 20 mm (360.0 vs 332.7 mm(2), p=0.64). Mean brainstem exposure was
      significantly greater with the far lateral approach for 0 mm (127.8 vs 65.8
      mm(2), p<0.01), 10 mm (129.5 vs 87.5 mm(2), p=0.045), and 15 mm (140.1 vs 97.8
      mm(2), p=0.01) lesions. There was no difference at 20 mm (146.7 vs 147.8 mm(2),
      p=0.97). Medial-lateral surgical freedom was greater with the far lateral
      approach for all sizes. The results of this study provide insight on one
      important variable in the decision-making process to select the optimal approach
      for anterolateral CVJ tumors.

PMID- 24290906
TI  - Comprehensibility of universal healthcare symbols for wayfinding in healthcare
      facilities.
AB  - Healthcare facilities are often complex and overwhelming for visitors, and
      wayfinding in healthcare facilities can be challenging. As there is an increasing
      number of global citizens who travel to seek medical care in another country, it
      is critical to make wayfinding easy for visitors who are not familiar with the
      language in a foreign country. Among many wayfinding aids, symbols are helpful
      for those visitors who have limited ability to understand written language. This
      study tested universal healthcare symbols in the United States, South Korea, and
      Turkey to compare the comprehension of symbols cross-country and identify
      predictors of the correct comprehension. To explore statistically significant
      relationships between symbol comprehension and countries, Pearson's Chi-square
      tests, logistic regression, and ANOVA were conducted. The test results showed
      that ten symbols among 14 tested have significant relationship with countries.
      Results of this study demonstrate that symbol comprehension can be varied
      significantly in different countries.

PMID- 24290907
TI  - Growing up after extremely preterm birth: lifespan mental health outcomes.
AB  - There is growing interest in the long-term mental health sequelae of extremely
      preterm birth. In this paper we review literature relating to mental health
      outcomes across the lifespan. Studies conducted in the preschool years, school
      age and adolescence, and adulthood show continuity in outcomes and point to an
      increased risk for inattention, socio-communicative problems and emotional
      difficulties in individuals born extremely preterm. Both behavioural and
      neuroimaging studies also provide evidence of a neurodevelopmental origin for
      mental health disorders in this population. Here we summarise contemporary
      evidence and highlight key methodological considerations for carrying out and
      interpreting studies in this field. 

PMID- 24290908
TI  - Cerebral palsy and developmental coordination disorder in children born preterm.
AB  - Children born early (<37 weeks of gestation) are at high risk of a range of motor
      impairments due to a variety of biological and environmental risk factors.
      Cerebral palsy occurs more frequently in those children born preterm, with the
      risk increasing with decreasing gestational age. Mild and moderate motor
      impairments, consistent with developmental coordination disorder, occur in almost
      half of those children born preterm and include difficulties with balance, manual
      dexterity and ball skills. All forms of motor impairment are associated with
      comorbidities, which may have a greater effect on quality of life, academic
      achievement and participation in extracurricular activities than the motor
      impairment itself. Infants at risk of motor impairment can be identified in early
      infancy with a combination of clinical assessment tools and perinatal risk
      factors. However, the reliable diagnosis of motor impairment requires follow-up
      into early childhood and it is important to ensure that the appropriate
      intervention is implemented. 

PMID- 24290909
TI  - Is dietetic treatment for undernutrition in older individuals in primary care
      cost-effective?
AB  - OBJECTIVES: Undernutrition in older age is associated with adverse clinical
      outcomes and high health care costs. This study aimed to evaluate the cost
      effectiveness of a dietetic treatment in primary care compared with usual care in
      older, undernourished, community-dwelling individuals. DESIGN: A parallel
      randomized controlled trial. SETTING: Primary care. PARTICIPANTS: A total of 146
      undernourished, independently living older (>=65 years) individuals.
      INTERVENTION: Dietetic treatment. MEASUREMENTS: Main outcomes were change in
      kilogram body weight compared with baseline and quality-adjusted life years
      (QALYs) after 6 months. Costs were measured from a societal perspective. The main
      analysis was performed according to the intention-to-treat principle. Multiple
      imputation was used to impute missing data and bootstrapping was used to estimate
      uncertainty surrounding cost differences and incremental cost-effectiveness
      ratios. Cost-effectiveness planes and cost-effectiveness acceptability curves
      were estimated. RESULTS: The participants were randomized to receive either
      dietetic treatment (n = 72) or usual care (n = 74). After 6 months, no
      statistically significant differences were found between the dietetic treatment
      and usual care group in body weight change (mean difference 0.78 kg, 95% CI -0.26
      1.82), QALYs (mean difference 0.001, 95% CI -0.04-0.04) and total costs (mean
      difference ?1645, 95% CI -525-3547). The incremental cost-utility ratio (ICUR)
      for QALYs was not interpretable. The incremental cost-effectiveness ratio (ICER)
      for body weight gain was 2111. The probability that dietetic treatment is cost
      effective compared with usual care was 0.78 for a ceiling ratio of ?5000 for body
      weight and 0.06 for a ceiling ratio of ?20.000 for QALY. CONCLUSION: In this
      study, dietetic treatment in older, undernourished, community-dwelling
      individuals was not cost-effective compared with usual care.

PMID- 24290910
TI  - A systematic review of malnutrition screening tools for the nursing home setting.
AB  - RATIONALE: Malnutrition screening among nursing home residents is often performed
      with tools developed for use among older subjects, and sometimes with tools
      designed for an adult population. Only a few tools have been designed
      specifically for the nursing home setting. This systematic review assesses the
      criterion and predictive validity of malnutrition screening tools used in nursing
      homes. METHODS: The databases MEDLINE, CINAHL, and EMBASE were searched on
      January 30, 2013, for manuscripts including search terms for malnutrition,
      screening or assessment tools, and setting. Articles were eligible for inclusion
      if they expressed criterion validity (how well can a tool assess nutritional
      status) or predictive validity (how well can a tool predict clinical outcome) of
      malnutrition screening tools in a nursing home population. Included were articles
      that had been published in the English, German, French, Dutch, Spanish, or
      Portuguese language. RESULTS: The search yielded 8313 references. Of these, 24
      met the inclusion criteria and were available; 2 extra manuscripts were retrieved
      by reference checking. Twenty tools were identified. Seventeen studies reported
      on criterion validity, and 9 on predictive validity. Four of the tools had been
      designed specifically for use in long term care. None of the tools, not even the
      ones specifically designed for the nursing home setting, performed (on average)
      better than "fair" in either assessing the residents' nutritional status or in
      predicting malnutrition-related outcomes. CONCLUSION: The use of existing
      screening tools for the nursing home population carries limitations, as none
      performs better than "fair" in assessing nutritional status or in predicting
      outcome. Also, no superior tool can be pointed out. This systematic review
      implies that further considerations regarding malnutrition screening among
      nursing home residents are required.

PMID- 24290912
TI  - Professional recognition of female and male doctors.
AB  - PRECEDENTS AND AIM: The awards for the excellence of the Official College of
      Physicians of Barcelona (COMB) were instituted in 2004 to recognize the
      excellence of the professional exercise. The winners are yearly chosen by juries
      appointed by the board of government, whose members propose for the award doctors
      who, in their opinion, have an exemplary professional and human behaviour.
      SUBJECTS AND METHODS: The number of male and female doctors who have obtained
      this recognition has been analysed in relation with the sex distribution in the
      juries. Likewise it has been compared the ratios men-to-women of those who have
      been rewarded and this ratio among physicians of more than 45 years. RESULTS:
      Between the awarded physicians the ratio men-to-women was of 2.7/1 (range, from
      1.2/1 for awardees in primary care to 6/1 in research). The men-to-women ratio
      among those who were awarded was in parallel to the man-to-women ratios of the
      juries. The ratio between men and women among members of the COMB of more than 45
      years was 1.4/1, whereas in those who were awarded it was of 2.7/1. The increase
      in the proportion of women in the juries in the last four years has been followed
      by an increase in the number of female physicians awarded. CONCLUSION: This data
      demonstrates that the predominance of male doctors among those who were awarded
      does not depend so much on the age factor, but basically on the proportion of
      male and female doctors in the juries.

PMID- 24290911
TI  - Neonatal Fc receptor expression in dendritic cells mediates protective immunity
      against colorectal cancer.
AB  - Cancers arising in mucosal tissues account for a disproportionately large
      fraction of malignancies. Immunoglobulin G (IgG) and the neonatal Fc receptor for
      IgG (FcRn) have an important function in the mucosal immune system that we have
      now shown extends to the induction of CD8(+) T cell-mediated antitumor immunity.
      We demonstrate that FcRn within dendritic cells (DCs) was critical for
      homeostatic activation of mucosal CD8(+) T cells that drove protection against
      the development of colorectal cancers and lung metastases. FcRn-mediated tumor
      protection was driven by DCs activation of endogenous tumor-reactive CD8(+) T
      cells via the cross-presentation of IgG complexed antigens (IgG IC), as well as
      the induction of cytotoxicity-promoting cytokine secretion, particularly
      interleukin-12, both of which were independently triggered by the FcRn-IgG IC
      interaction in murine and human DCs. FcRn thus has a primary role within mucosal
      tissues in activating local immune responses that are critical for priming
      efficient anti-tumor immunosurveillance.

PMID- 24290913
TI  - Bacteriophage 933W encodes a functional esterase downstream of the Shiga toxin 2a
      operon.
AB  - In this study, the 1938bp open reading frame z1466, which is encoded directly
      downstream the Shiga toxin 2a (Stx2a) operon in E. coli O157:H7 phage 933W was
      cloned and expressed recombinantly. Purification with Ni-NTA agarose beads with
      subsequent SDS-PAGE revealed a 68kDa protein, designated 933Wp42-His. Analysis of
      933Wp42-His demonstrated an esterase activity by activity staining of native gels
      using triacetin as a substrate. Purified 933Wp42-His demonstrated a Km value of
      about 10mM and a Vmax value of 1.667nkat/ml for 4-methylumbelliferyl-acetate (4
      MUF-Ac) as a substrate. The enzyme was most active in the pH-range of 7.0-8.0,
      and at 50 degrees C. Furthermore, 933Wp42-His was able to hydrolyze acetic acid
      from mucin, and 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2). This is the
      first description of an enzymatic activity of the Stx-phage-encoded protein
      933Wp42. Its role in substrate utilization during colonization and human
      infection is discussed. 

PMID- 24290914
TI  - Mitigating the effect of non-stationarity in spectral analysis-an application to
      neonate heart rate analysis.
AB  - In order to mitigate the effect of non-stationarity in frequency domain analysis
      of data, we propose a modification to the power spectral estimation, a widely
      used technique to characterize physiological signals. Spectral analysis requires
      partitioning data into smaller epochs determined by the desired frequency
      resolution. The modified approach proposed here involves dividing the data within
      each epoch by the standard deviation of the data for that epoch. We applied this
      modified approach to cardiac beat-to-beat interval data recorded from a newborn
      infant undergoing hypothermia treatment for birth asphyxia. The critically ill
      infant had episodes of tachyarrhythmia, distributed sporadically throughout the
      study, which affected the stationarity of the heart rate. Over the period of
      continuous heart rate recording, the infant's clinical course deteriorated
      progressively culminating in death. Coinciding with this clinical deterioration,
      the heart rate signal showed striking changes in both low-frequency and high
      frequency power indicating significant impairment of the autonomic nervous
      system. The standard spectral approach failed to capture these phenomena because
      of the non-stationarity of the signal. Conversely, the modified approach proposed
      here captured the deteriorating physiology of the infant clearly. 

PMID- 24290915
TI  - Mathematical modeling of brain glioma growth using modified reaction-diffusion
      equation on brain MR images.
AB  - In this paper, a modified reaction-diffusion model is proposed for modeling the
      diffusion of brain glioma cells. Unlike the other models, a weighted parameter is
      introduced, which balances the diffusion coefficient of the grey and white
      matters. Anisotropic characteristics of the model are represented. A local region
      similarity measure (local Bhattacharyya distance) determines the weighted
      parameter. Experimental results demonstrate the effectiveness and accuracy of the
      modified reaction diffusion equation with a weighted parameter for real brain
      glioma MR images. 

PMID- 24290916
TI  - Baseline characteristics of cervical auscultation signals during various head
      maneuvers.
AB  - Cervical auscultation (CA) is an emerging method of assessing swallowing
      disorders that is both non-invasive and inexpensive. This technique utilizes
      microphones to detect acoustic sounds produced by swallowing activity and
      characterize its behavior. Though some properties of swallowing sounds are known,
      there is still a need for a complete understanding of the baseline
      characteristics of cervical auscultation signals as well as how they change due
      to the patient's head motion, age, and sex. In order to examine these parameters,
      data was collected from 56 healthy adult participants that performed six
      different head movement tasks without swallowing. After preprocessing the signal,
      features were extracted. Dependent variables were time domain, frequency domain
      and time-frequency domain features. Statistical tests showed that only the
      skewness and peak frequency were not statistically different for all tasks. The
      peak frequency results indicate that head movement does not significantly affect
      the microphone signal, and that it is unnecessary to filter out the lowest
      frequency components. No sex differences were observed in the extracted features,
      but several features exhibited age dependence. 

PMID- 24290917
TI  - Modeling chronic hepatitis B or C virus infection during antiviral therapy using
      an analogy to enzyme kinetics: long-term viral dynamics without rebound and
      oscillation.
AB  - The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)
      infection during therapy enables us to analyze short-term viral kinetics.
      However, the model is not useful for analyzing long-term viral kinetics. Here, I
      suggest a new model that was obtained by introducing Michaelis-Menten kinetics
      into the basic model. The new model can exhibit long-term viral kinetics without
      rebound and oscillation, unlike the basic model. The value of the parameter K in
      the new model is analogous to the Michaelis constant Km and is predicted to be
      approximately less than 10(10)/ml. 

PMID- 24290918
TI  - Accelerating in silico research with workflows: a lesson in Simplicity.
AB  - Bioinformatics is the application of computer science and related disciplines to
      the field of molecular biology. While there are currently several web based and
      desktop tools available for biologists to perform routine bioinformatics tasks,
      these tools often require users to manually and repeatedly co-ordinate multiple
      applications before reaching a result. In an effort to reduce time and error,
      workflow tools have been developed to automate these tasks. However, many of
      these tools require expert knowledge of the techniques and supporting databases
      which more often than not lies outside the scope of most biologists. Herein, we
      describe the development of sequence information management platform
      (Simplicity), a workflow-based bioinformatics management tool, which allows non
      bioinformaticians to rapidly annotate large amounts of DNA and protein sequence
      data. 

PMID- 24290919
TI  - Line filtering for surgical tool localization in 3D ultrasound images.
AB  - We present a method for automatic surgical tool localization in 3D ultrasound
      images based on line filtering, voxel classification and model fitting. This
      could possibly provide assistance for biopsy needle or micro-electrode insertion,
      or a robotic system performing this insertion. The line-filtering method is first
      used to enhance the contrast of the 3D ultrasound image, then a classifier is
      chosen to separate the tool voxels, in order to reduce the number of outliers.
      The last step is Random Sample Consensus (RANSAC) model fitting. Experimental
      results on several different polyvinyl alcohol (PVA) cryogel data sets
      demonstrate that the failure rate of the method proposed herein is improved by at
      least 86% compared to the model-fitting RANSAC algorithm with axis accuracy
      better than 1mm, at the expense of only a modest increase in computational
      effort. The results of this experiment show that this system could be useful for
      clinical applications. 

PMID- 24290920
TI  - Virtual reality aided visualization of fluid flow simulations with application in
      medical education and diagnostics.
AB  - Medical education, training and preoperative diagnostics can be drastically
      improved with advanced technologies, such as virtual reality. The method proposed
      in this paper enables medical doctors and students to visualize and manipulate
      three-dimensional models created from CT or MRI scans, and also to analyze the
      results of fluid flow simulations. Simulation of fluid flow using the finite
      element method is performed, in order to compute the shear stress on the artery
      walls. The simulation of motion through the artery is also enabled. The virtual
      reality system proposed here could shorten the length of training programs and
      make the education process more effective. 

PMID- 24290921
TI  - Support vector machine algorithms in the search of KIR gene associations with
      disease.
AB  - Killer-cell immunoglobulin-like receptors (KIR) are membrane proteins expressed
      by natural killer cells and CD8 lymphocytes. The KIR system consists of 17 genes
      and 614 alleles, some of which bind human leukocyte antigens (HLA). Both KIR and
      HLA modulate susceptibility to haematological malignancies, viral infections and
      autoimmune diseases. Molecular epidemiology studies employ traditional
      statistical methods to identify links between KIR genes and disease. Here we
      describe our results at applying artificial intelligence algorithms (support
      vector machines) to identify associations between KIR genes and disease. We
      demonstrate that these algorithms are capable of classifying samples into healthy
      and diseased groups based solely on KIR genotype with potential use in clinical
      decision support systems. 

PMID- 24290922
TI  - Homology modeling, molecular docking and MD simulation studies to investigate
      role of cysteine protease from Xanthomonas campestris in degradation of Abeta
      peptide.
AB  - Cysteine protease is known to degrade amyloid beta peptide which is a causative
      agent of Alzheimer's disease. This cleavage mechanism has not been studied in
      detail at the atomic level. Hence, a three-dimensional structure of cysteine
      protease from Xanthomonas campestris was constructed by homology modeling using
      Geno3D, SWISS-MODEL, and MODELLER 9v7. All the predicted models were analyzed by
      PROCHECK and PROSA. Three-dimensional model of cysteine protease built by
      MODELLER 9v7 shows similarity with human cathepsin B crystal structure. This
      model was then used further for docking and simulation studies. The molecular
      docking study revealed that Cys17, His87, and Gln88 residues of cysteine protease
      form an active site pocket similar to human cathepsin B. Then the docked complex
      was refined by molecular dynamic simulation to confirm its stable behavior over
      the entire simulation period. The molecular docking and MD simulation studies
      showed that the sulfhydryl hydrogen atom of Cys17 of cysteine protease interacts
      with carboxylic oxygen of Lys16 of Abeta peptide indicating the cleavage site.
      Thus, the cysteine protease model from X. campestris having similarity with human
      cathepsin B crystal structure may be used as an alternate approach to cleave
      Abeta peptide a causative agent of Alzheimer's disease. 

PMID- 24290923
TI  - A joint sparse representation-based method for double-trial evoked potentials
      estimation.
AB  - In this paper, we present a novel approach to solving an evoked potentials
      estimating problem. Generally, the evoked potentials in two consecutive trials
      obtained by repeated identical stimuli of the nerves are extremely similar. In
      order to trace evoked potentials, we propose a joint sparse representation-based
      double-trial evoked potentials estimation method, taking full advantage of this
      similarity. The estimation process is performed in three stages: first, according
      to the similarity of evoked potentials and the randomness of a spontaneous
      electroencephalogram, the two consecutive observations of evoked potentials are
      considered as superpositions of the common component and the unique components;
      second, making use of their characteristics, the two sparse dictionaries are
      constructed; and finally, we apply the joint sparse representation method in
      order to extract the common component of double-trial observations, instead of
      the evoked potential in each trial. A series of experiments carried out on
      simulated and human test responses confirmed the superior performance of our
      method. 

PMID- 24290924
TI  - Numerical investigation into blood clotting at the bone-dental implant interface
      in the presence of an electrical stimulus.
AB  - The insertion of a dental implant activates a sequence of wound healing events
      ending with bone formation and implant osseointegration. This sequence starts
      with the blood coagulation process and the formation of a fibrin network that
      detains spilt blood. Fibrin formation can be simplified as the kinetic reaction
      between thrombin and fibrinogen preceding the conversion of fibrinogen into
      fibrin. Based on experimental observations of the electrical properties of these
      molecules, we present a hypothesis for the mechanism of a static electrical
      stimulus in controlling the formation of the blood clot. Specifically, the
      electrical stimulus increases the fibrin network formation in such a way that a
      preferential region of higher fibrin density is obtained. This hypothesis is
      validated by means of a numerical model for the blood clot formation at the bone
      dental implant interface. Numerical results compare favorably to experimental
      observations for blood clotting with and without the static electrical stimulus.
      It is concluded that the density of the fibrin network depends on the strength of
      the static electrical stimulus, and that the blood clot formation has a
      preferential direction of formation in the presence of the electrical signal. 

PMID- 24290925
TI  - Optimal drug regimens in cancer chemotherapy: a multi-objective approach.
AB  - In this paper, based on two mathematical models, a set of optimal anticancer drug
      regimens is designed. Two important difficulties in treating cancers with
      chemotherapy are drug resistance and toxicity. They were considered in our
      treatment design; a compartmental model was extended to appropriately describe
      drug resistance and two constraints were imposed on the value of the anticancer
      drug dynamics to avoid toxicity. Indeed, we optimized two objective functions
      simultaneously in order to minimize the size of the tumor as well as the side
      effects of the anticancer drug on the patient's body. Operating the described
      task, a bi-objective optimization problem was defined and solved by an
      evolutionary method. This optimization led to a set of optimal drug regimens,
      which can be used in several chemotherapy treatments. Numerical simulations were
      given to illustrate the flexibility of the method. 

PMID- 24290926
TI  - Impact of TGF-b on breast cancer from a quantitative proteomic analysis.
AB  - There has been much active research in bioinformatics to support our
      understanding of oncogenesis and tumor progression. Most research relies on mRNA
      gene expression data to identify marker genes or cancer specific gene networks.
      However, considering that proteins are functional molecules that carry out the
      biological tasks of genes, they can be direct markers of biological functions.
      Protein abundance data on a genome scale have not been investigated in depth due
      to the limited availability of high throughput protein assays. This hindrance is
      chiefly caused by a lack of robust techniques such as RT-PCR (real-time
      polymerase chain reaction). In this study, we quantified phospho-proteomes of
      breast cancer cell lines treated with TGF-beta (transforming growth factor beta).
      To discover biomarkers and observe changes in the signaling pathways related to
      breast cancer, we applied a protein network-based approach to generate a
      classifier of subnet markers. The accuracy of that classifier outperformed other
      network-based classification algorithms, and current feature selection and
      classification algorithms. Moreover, many cancer-related proteins were identified
      in those sub-networks. Each sub-network provides functional insights and can
      serve as a potential marker for TGF-beta treatments. After interpreting the roles
      of proteins in sub-networks with various signaling pathways, we found strong
      candidate proteins and various related interactions that are expected to affect
      breast cancer outcomes. These results demonstrate the high quality of the
      quantified phospho-proteomes data and show that our network construction and
      classification method is appropriate for an analysis of this type of data. 

PMID- 24290927
TI  - Algorithms for scheduling of chemotherapy plans.
AB  - Chemotherapy is used to control and cure cancer by using drugs to destroy cancer
      cells. Treatment schedules for chemotherapy may vary depending on the type of
      cancer, the goals of treatment, the type of chemotherapy and the patient's state
      of health. Chemotherapy is usually given in cycles of a treatment-period followed
      by a rest-period. An oncologist decides the choice of a particular regimen;
      however, modifications to drug dose and schedule are often necessary because of
      variabilities in the health of an individual patient. Therefore an orderly
      execution of chemotherapy regimens requires management, scheduling and allocation
      of the resources available. Chemotherapy scheduling is an optimization problem.
      In this paper, a two-phase approach has been adopted to deal with the problem. An
      adaptive negative-feedback scheduling algorithm is proposed for the first phase
      to control the load on the system. Two heuristics based on the 'Multiple Knapsack
      Problem' have been evaluated for the second phase to assign patients to specific
      infusion seats. The overall design has been put to test at a local chemotherapy
      center and has yielded good results for patient waiting times, orderly execution
      of chemotherapy regimen and utilization of infusion chairs. 

PMID- 24290928
TI  - Automatic classification of infant sleep based on instantaneous frequencies in a
      single-channel EEG signal.
AB  - This study presents a novel approach for the electroencephalogram (EEG) signal
      quantification in which the empirical mode decomposition method, a time-frequency
      method designated for nonlinear and non-stationary signals, decomposes the EEG
      signal into intrinsic mode functions (IMF) with corresponding frequency ranges
      that characterize the appropriate oscillatory modes embedded in the brain neural
      activity acquired using EEG. To calculate the instantaneous frequency of IMFs, an
      algorithm was developed using the Generalized Zero Crossing method. From the
      resulting frequencies, two different novel features were generated: the median
      instantaneous frequencies and the number of instantaneous frequency changes
      during a 30s segment for seven IMFs. The sleep stage classification for the
      daytime sleep of 20 healthy babies was determined using the Support Vector
      Machine classification algorithm. The results were evaluated using the cross
      validation method to achieve an approximately 90% accuracy and with new examinee
      data to achieve 80% average accuracy of classification. The obtained results were
      higher than the human experts' agreement and were statistically significant,
      which positioned the method, based on the proposed features, as an efficient
      procedure for automatic sleep stage classification. The uniqueness of this study
      arises from newly proposed features of the time-frequency domain, which bind
      characteristics of the sleep signals to the oscillation modes of brain activity,
      reflecting the physical characteristics of sleep, and thus have the potential to
      highlight the congruency of twin pairs with potential implications for the
      genetic determination of sleep. 

PMID- 24290929
TI  - A classification system based on a new wrapper feature selection algorithm for
      the diagnosis of primary and secondary polycythemia.
AB  - Primary and Secondary Polycythemia are diseases of the bone marrow that affect
      the blood's composition and prohibit patients from becoming blood donors. Since
      these diseases may become fatal, their early diagnosis is important. In this
      paper, a classification system for the diagnosis of Primary and Secondary
      Polycythemia is proposed. The proposed system classifies input data into three
      classes; Healthy, Primary Polycythemic (PP) and Secondary Polycythemic (SP) and
      is implemented using two separate binary classification levels. The first level
      performs the Healthy/non-Healthy classification and the second level the PP/SP
      classification. To this end, a novel wrapper feature selection algorithm, called
      the LM-FM algorithm, is presented in order to maximize the classifier's
      performance. The algorithm is comprised of two stages that are applied
      sequentially: the Local Maximization (LM) stage and the Floating Maximization
      (FM) stage. The LM stage finds the best possible subset of a fixed predefined
      size, which is then used as an input for the next stage. The FM stage uses a
      floating size technique to search for an even better solution by varying the
      initially provided subset size. Then, the Support Vector Machine (SVM) classifier
      is used for the discrimination of the data at each classification level. The
      proposed classification system is compared with various well-established feature
      selection techniques such as the Sequential Floating Forward Selection (SFFS) and
      the Maximum Output Information (MOI) wrapper schemes, and with standalone
      classification techniques such as the Multilayer Perceptron (MLP) and SVM
      classifier. The proposed LM-FM feature selection algorithm combined with the SVM
      classifier increases the overall performance of the classification system,
      scoring up to 98.9% overall accuracy at the first classification level and up to
      96.6% at the second classification level. Moreover, it provides excellent
      robustness regardless of the size of the input feature subset used. 

PMID- 24290930
TI  - The dominant morphology of fractionated atrial electrograms has greater temporal
      stability in persistent as compared with paroxysmal atrial fibrillation.
AB  - BACKGROUND: Measurements of both the dominant frequency (DF) and the time series
      morphology of complex fractionated atrial electrograms (CFAE) are useful to
      distinguish persistent from paroxysmal atrial fibrillation (AF). In this study,
      an algorithm was devised to extract morphologic components according to
      frequency, and its usefulness for distinguishing CFAE was shown. METHOD: CFAE of
      length 16s were obtained at two sites each from the four pulmonary vein ostia
      (PV), and from anterior and posterior left atrial free wall (FW), in nine
      paroxysmal and 10 longstanding persistent AF patients. The DF was computed for
      each of two 8s CFAE segments in each 16s recording. Each CFAE segment was then
      transformed into a set of basis vectors, which represent electrogram morphology
      at each frequency. The dominant morphology (DM) is defined as the ensemble
      average of sequential signal segments, with the segment length equal to the
      period at the DF. The DMs of the two 8s pairs were correlated. Normalized
      correlation coefficients were tabulated for all data, and separately for PV and
      FW. The means and coefficients of variation of the DM correlation coefficients
      were then plotted, and a linear discriminant function was used to classify
      persistent versus paroxysmal AF data. For comparison with DM results, CFE-mean
      and interval confidence level (ICL) were also calculated for persistent versus
      paroxysmal AF data. RESULTS: Mean correlation of the DM, 1st 8s versus 2nd 8s
      data, was 0.62+0.22 for persistent versus 0.50+0.19 for paroxysmal CFAE for all
      recording sites (p<0.001). At single anatomical locations, correlation was
      greater in persistents than paroxysmals at all sites, but achieved significance
      only at the left superior (p<0.001) and right superior (p<0.05) PV. Spatial
      variation in correlation coefficient was greater in paroxysmal than persistent AF
      (not significant). Using the means of DF correlation coefficients, 17/19 patients
      were classified correctly. The CFE-mean parameter averaged 89.01+/-20.99 ms in
      persistents versus 93.96+/-33.81 ms in paroxysmals (p<0.05), while ICL averaged
      94.54+/-18.52 deflections/8s for persistents versus 90.70+/-19.28 deflections/8s
      for paroxysmals (p<0.05). CONCLUSIONS: In CFAE recordings, the DM parameter was
      found to have greater temporal morphologic variation in paroxysmal as compared
      with persistent AF data (p<0.001). In contrast, only moderate significance
      between paroxysmal versus persistent AF data was found when using the of CFE-mean
      and ICL parameters (p<0.05). The DM parameter may thus be useful as a new measure
      to discern both temporal and spatial variations in CFAE in paroxysmal versus
      persistent AF recordings.

PMID- 24290931
TI  - Computer-aided diagnosis of diabetic retinopathy: a review.
AB  - Diabetes mellitus may cause alterations in the retinal microvasculature leading
      to diabetic retinopathy. Unchecked, advanced diabetic retinopathy may lead to
      blindness. It can be tedious and time consuming to decipher subtle morphological
      changes in optic disk, microaneurysms, hemorrhage, blood vessels, macula, and
      exudates through manual inspection of fundus images. A computer aided diagnosis
      system can significantly reduce the burden on the ophthalmologists and may
      alleviate the inter and intra observer variability. This review discusses the
      available methods of various retinal feature extractions and automated analysis. 

PMID- 24290932
TI  - Ensemble selection for feature-based classification of diabetic maculopathy
      images.
AB  - As diabetic maculopathy (DM) is a prevalent cause of blindness in the world, it
      is increasingly important to use automated techniques for the early detection of
      the disease. In this paper, we propose a decision system to classify DM fundus
      images into normal, clinically significant macular edema (CMSE), and non
      clinically significant macular edema (non-CMSE) classes. The objective of the
      proposed decision system is three fold namely, to automatically extract textural
      features (both region specific and global), to effectively choose subset of
      discriminatory features, and to classify DM fundus images to their corresponding
      class of disease severity. The system uses a gamut of textural features and an
      ensemble classifier derived from four popular classifiers such as the hidden
      naive Bayes, naive Bayes, sequential minimal optimization (SMO), and the tree
      based J48 classifiers. We achieved an average classification accuracy of 96.7%
      using five-fold cross validation. 

PMID- 24290933
TI  - Nonparametric optimization of constrained total variation for tomography
      reconstruction.
AB  - Iterative algorithms based on constrained total-variation (TV) optimization are
      effective for the reconstruction of limited data from X-ray computed tomography
      (CT). Such algorithms can be executed by implementing alternative operations
      projection onto convex sets (POCS) on the constraints, and a gradient descent
      approach for TV objective minimization. To balance TV-gradient descent with POCS,
      the adaptive-steepest-descent (ASD) method utilizes a set of complicated
      parameters to adjust the TV-gradient-descent step-size. The optimal parameters
      are difficult for users to select, and moreover, users have to empirically choose
      different parameters when reconstructing different types of images. To deal with
      these drawbacks, this paper proposes a nonparametric method for constrained TV
      optimization. The method automatically updates the step-size of TV iteration
      according to the changes in the consistency term defined by the constraints
      without introducing artificial parameters. The proposed method avoids the time
      consuming parameter optimization, and can be conveniently implemented in various
      applications. Experimental results on phantom data demonstrate the flexibility
      and effectiveness of the proposed method. 

PMID- 24290934
TI  - Numerical simulation of glottal flow.
AB  - In cases of permanent immobility of both vocal folds patients have difficulties
      with breathing but rarely with voicing. However, clinical experience shows that
      the shape of the larynx (voice box) seems to have a significant influence on the
      degree of airflow and breathing pattern. In order to find an optimal geometry of
      the larynx in terms of easiness for breathing after the surgical change of vocal
      folds or false vocal cords (ventricular folds), a set of numerical simulations of
      glottal flow for weakly compressible Navier-Stokes equations has been performed.
      We compare airflow resistance and volumetric flow rate for several geometry
      concepts for inspiration as well as expiration. Finally, we discuss the optimal
      geometry with respect to the quality of breathing. 

PMID- 24290935
TI  - Estimating cognitive workload using wavelet entropy-based features during an
      arithmetic task.
AB  - Electroencephalography (EEG) has shown promise as an indicator of cognitive
      workload; however, precise workload estimation is an ongoing research challenge.
      In this investigation, seven levels of workload were induced using an arithmetic
      task, and the entropy of wavelet coefficients extracted from EEG signals is shown
      to distinguish all seven levels. For a subject-independent multi-channel
      classification scheme, the entropy features achieved high accuracy, up to 98% for
      channels from the frontal lobes, in the delta frequency band. This suggests that
      a smaller number of EEG channels in only one frequency band can be deployed for
      an effective EEG-based workload classification system. Together with analysis
      based on phase locking between channels, these results consistently suggest
      increased synchronization of neural responses for higher load levels. 

PMID- 24290936
TI  - Aortic root 3D parametric morphological model from 2D-echo images.
AB  - The gold standard for the study of the macro-anatomy of the aortic root are multi
      detector computed tomography (MDCT) and magnetic resonance (MR) imaging. Both
      technologies have major advantages and limitations. Although 4D echo is entering
      the study of the aortic root, 2D echo is the most commonly used diagnostic tool
      in daily practice. We designed and developed an algorithm for 3D modeling of the
      aortic root based on measures taken routinely at 2D echocardiography from 20
      healthy individuals with normal aortic root. The tool was then translated in 12
      patients who underwent both echo and MDCT. The results obtained with the 3D
      modeling program were quantitatively and qualitatively compared with 3D
      reconstruction from MDCT. Ad hoc ratios describing the morphology of the aortic
      root in MDCT and in the 3D model were used for comparison. In 12 patients with
      aortic root dilatation, the ratios obtained with our model are in good agreement
      with those from MDCT. Linear correlation for both long axis and short axis ratios
      was strong. The 3D modeling software can be easily adopted by cardiologists
      routinely involved in clinical evaluation of the pathology of the aortic root.
      The tool is easy to apply, does not require additional costs, and may be used to
      generate a set of data images for monitoring the evolution of the morphology and
      dimension of the aortic root, flanking the 3D MDCT and MR that remain the gold
      standard tools. 

PMID- 24290937
TI  - Usability testing of a respiratory interface using computer screen and facial
      expressions videos.
AB  - Computer screen videos (CSVs) and users' facial expressions videos (FEVs) are
      recommended to evaluate systems performance. However, software combining both
      methods is often non-accessible in clinical research fields. The Observer-XT
      software is commonly used for clinical research to assess human behaviours. Thus,
      this study reports on the combination of CSVs and FEVs, to evaluate a graphical
      user interface (GUI). Eight physiotherapists entered clinical information in the
      GUI while CSVs and FEVs were collected. The frequency and duration of a list of
      behaviours found in FEVs were analysed using the Observer-XT-10.5.
      Simultaneously, the frequency and duration of usability problems of CSVs were
      manually registered. CSVs and FEVs timelines were also matched to verify
      combinations. The analysis of FEVs revealed that the category most frequently
      observed in users behaviour was the eye contact with the screen (ECS, 32+/-9)
      whilst verbal communication achieved the highest duration (14.8+/-6.9min).
      Regarding the CSVs, 64 problems, related with the interface (73%) and the user
      (27%), were found. In total, 135 usability problems were identified by combining
      both methods. The majority were reported through verbal communication (45.8%) and
      ECS (40.8%). "False alarms" and "misses" did not cause quantifiable reactions and
      the facial expressions problems were mainly related with the lack of familiarity
      (55.4%) felt by users when interacting with the interface. These findings
      encourage the use of Observer-XT-10.5 to conduct small usability sessions, as it
      identifies emergent groups of problems by combining methods. However, to validate
      final versions of systems further validation should be conducted using
      specialized software. 

PMID- 24290938
TI  - Using positive and negative patterns to extract information from journal articles
      regarding the regulation of a target gene by a transcription factor.
AB  - Gene regulation research concerns the regulatory relationship between
      transcription factors (TFs) and their target genes (TGenes). Due to the rapid
      acceleration of biological research, it is impractical for biologists to read all
      of the relevant literature and manually extract all of the information about the
      regulatory relationships between a TF and its TGenes. This paper proposes a
      method utilizing negative and positive textual patterns to extract regulatory
      information regarding certain TF-TGene pairs, which provides insightful
      information to biologists and saves them time from excessive literature reading.
      We hypothesized that the negative patterns could be used for filtering and that
      the system would mainly rely on the positive patterns to mine the regulatory TF
      TGene relationships from the text. We also examined whether WordNet could be
      utilized to improve the pattern recognition performance. The results show that
      the negative pattern should be used for initial filtering, and then the positive
      patterns can extract information related to gene regulation. Moreover, WordNet
      seems to have little effect on the performance when extracting gene regulations. 

PMID- 24290940
TI  - EEG-based emotion estimation using Bayesian weighted-log-posterior function and
      perceptron convergence algorithm.
AB  - This paper addresses the emotion recognition problem from electroencephalogram
      signals, in which emotions are represented on the valence and arousal dimensions.
      Fast Fourier transform analysis is used to extract features and the feature
      selection based on Pearson correlation coefficient is applied. This paper
      proposes a probabilistic classifier based on Bayes' theorem and a supervised
      learning using a perceptron convergence algorithm. To verify the proposed
      methodology, we use an open database. An emotion is defined as two-level class
      and three-level class in both valence and arousal dimensions. For the two-level
      class case, the average accuracy of the valence and arousal estimation is 70.9%
      and 70.1%, respectively. For the three-level class case, the average accuracy is
      55.4% and 55.2%, respectively. 

PMID- 24290939
TI  - A threshold fuzzy entropy based feature selection for medical database
      classification.
AB  - Feature selection is one of the most common and critical tasks in database
      classification. It reduces the computational cost by removing insignificant
      features. Consequently, this makes the diagnosis process accurate and
      comprehensible. This paper presents the measurement of feature relevance based on
      fuzzy entropy, tested with a Radial Basis Function Network classifier for a
      medical database classification. Three feature selection strategies are devised
      to obtain the valuable subset of relevant features. Five benchmarked datasets,
      which are available in the UCI Machine Learning Repository, have been used in
      this work. The classification accuracy shows that the proposed method is capable
      of producing good results with fewer features than the original datasets. 

PMID- 24290941
TI  - Gallbladder shape extraction from ultrasound images using active contour models.
AB  - Gallbladder function is routinely assessed using ultrasonographic (USG)
      examinations. In clinical practice, doctors very often analyse the gallbladder
      shape when diagnosing selected disorders, e.g. if there are turns or folds of the
      gallbladder, so extracting its shape from USG images using supporting software
      can simplify a diagnosis that is often difficult to make. The paper describes two
      active contour models: the edge-based model and the region-based model making use
      of a morphological approach, both designed for extracting the gallbladder shape
      from USG images. The active contour models were applied to USG images without
      lesions and to those showing specific disease units, namely, anatomical changes
      like folds and turns of the gallbladder as well as polyps and gallstones. This
      paper also presents modifications of the edge-based model, such as the method for
      removing self-crossings and loops or the method of dampening the inflation force
      which moves nodes if they approach the edge being determined. The user is also
      able to add a fragment of the approximated edge beyond which neither active
      contour model will move if this edge is incomplete in the USG image. The
      modifications of the edge-based model presented here allow more precise results
      to be obtained when extracting the shape of the gallbladder from USG images than
      if the morphological model is used. 

PMID- 24290942
TI  - Structured errors in reconstruction methods for Non-Cartesian MR data.
AB  - BACKGROUND: Reconstruction methods for Non-Cartesian magnetic resonance imaging
      have often been analyzed using the root mean square error (RMSE). However, RMSE
      is not able to measure the level of structured error associated with the
      reconstruction process. METHODS: An index for geometric information loss was
      presented using the 2D autocorrelation function. The performances of Least
      Squares Non Uniform Fast Fourier Transform (LS-NUFFT) and gridding reconstruction
      (GR) methods were compared. The Direct Summation method (DS) was used as
      reference. For both methods, RMSE and the loss in geometric information were
      calculated using a digital phantom and a hyperpolarized (13)C dataset. RESULTS:
      The performance of the geometric information loss index was analyzed in the
      presence of noise. Comparing to GR, LS-NUFFT obtained a lower RMSE, but its error
      image appeared more structured. This was observed in both phantom and in vivo
      experiments. DISCUSSION: The evaluation of geometric information loss together
      with the reconstruction error was important for an appropriate performance
      analysis of the reconstruction methods. The use of geometric information loss was
      helpful to determine that LS-NUFFT loses relevant information in the
      reconstruction process, despite the low RMSE.

PMID- 24290943
TI  - A new automatic image analysis method for assessing estrogen receptors' status in
      breast tissue specimens.
AB  - Manual assessment of estrogen receptors' (ER) status from breast tissue
      microscopy images is a subjective, time consuming and error prone process.
      Automatic image analysis methods offer the possibility to obtain consistent,
      objective and rapid diagnoses of histopathology specimens. In breast cancer
      biopsies immunohistochemically (IHC) stained for ER, cancer cell nuclei present a
      large variety in their characteristics that bring various difficulties for
      traditional image analysis methods. In this paper, we propose a new automatic
      method to perform both segmentation and classification of breast cell nuclei in
      order to give quantitative assessment and uniform indicators of IHC staining that
      will help pathologists in their diagnostic. Firstly, a color geometric active
      contour model incorporating a spatial fuzzy clustering algorithm is proposed to
      detect the contours of all cell nuclei in the image. Secondly, overlapping and
      touching nuclei are separated using an improved watershed algorithm based on a
      concave vertex graph. Finally, to identify positive and negative stained nuclei,
      all the segmented nuclei are classified into five categories according to their
      staining intensity and morphological features using a trained multilayer neural
      network combined with Fisher's linear discriminant preprocessing. The proposed
      method is tested on a large dataset containing several breast tissue images with
      different levels of malignancy. The experimental results show high agreement
      between the results of the method and ground-truth from the pathologist panel.
      Furthermore, a comparative study versus existing techniques is presented in order
      to demonstrate the efficiency and the superiority of the proposed method. 

PMID- 24290944
TI  - Maxwell's equations-based dynamic laser-tissue interaction model.
AB  - Since its invention in the early 1960s, the laser has been used as a tool for
      surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness
      with the greatest margin of safety it is important to understand the mechanisms
      of light propagation through tissue and how that light affects living cells.
      Lasers with novel output characteristics for medical and military applications
      are too often implemented prior to proper evaluation with respect to tissue
      optical properties and human safety. Therefore, advances in computational models
      that describe light propagation and the cellular responses to laser exposure,
      without the use of animal models, are of considerable interest. Here, a physics
      based laser-tissue interaction model was developed to predict the dynamic changes
      in the spatial and temporal temperature rise during laser exposure to biological
      tissues. Unlike conventional models, the new approach is grounded on the rigorous
      electromagnetic theory that accounts for wave interference, polarization, and
      nonlinearity in propagation using a Maxwell's equations-based technique. 

PMID- 24290945
TI  - Comparison of isometric and anatomical graft placement in synthetic ACL
      reconstructions: a pilot study.
AB  - Correct graft placement is critical to the success of anterior cruciate ligament
      reconstructions (ACLR). Whilst current trend is to insert the graft in an
      anatomical location, synthetic grafts have shown to better perform when they are
      located in an isometric position. Placement, however, is largely dependent on the
      surgeon and no consensus has been reached for synthetic grafts. Kinematic flexion
      extension data of four separate cadaveric knees was obtained using an optical
      tracking system. Knees were CT-scanned and computer models were developed for
      each specimen. Three different graft insertion techniques were simulated in each
      of the computer models. Kinematic data obtained from the optical tracking was
      applied to the 3D computer models to simulate knee flexion-extension, and virtual
      change in ACL graft length was measured over the cycle for each insertion
      technique. Length changes were plotted onto the Radiological-Quadrant. The
      isometric region on the femur was found to be a band spreading from the mid to
      deep end of the Blumensaat's line down to the shallow-inferior end of the femoral
      condyle. The JP Laboureau isometric point technique was consistently located in
      the isometric zone, with the following coordinates on the Radiographic-Quadrant:
      t=0.375 (SD 0.0066), h=0.227 (SD 0.0266). The Bernard-Hertel and Charlie Brown
      anatomical placement methods were located (13%, -6%) and (8%, -15%) away, from
      the JP Laboureau isometric point, respectively, based on t- and h- coordinates of
      the Radiographic-Quadrant. This study has determined the isometric region using
      three-dimensional analysis relative to the Radiographic-Quadrant. The JP
      Laboureau method best finds the isometric point. This information is useful for
      synthetic graft placement. 

PMID- 24290946
TI  - Perinatal women's perceptions about midwifery led model of care in secondary care
      hospitals in Karachi, Pakistan.
AB  - OBJECTIVE: the purpose of this study was to explore the perceptions and
      experiences of perinatal women who have availed of midwifery led model of care
      (MLC) at secondary care settings in Karachi, Pakistan. DESIGN: a qualitative
      descriptive exploratory approach using semi-structured interviews. PARTICIPANTS:
      a purposive sample of 10 women who had used MLC was enroled from each site.
      FINDINGS: content analysis highlighted that 'women's satisfaction with MLC'
      emerged as the main theme and, under this theme, the six categories that emerged
      were: (1) the admired capability and maturity of midwives, (2) the affordability
      of midwifery services, (3) a personalised relationship, (4) the empowerment of
      women to make decisions, (5) presence, and (6) a voiced concern regarding lack of
      marketing of MLC. KEY CONCLUSIONS: the study findings revealed that women had an
      overall feeling of satisfaction with the maternity care provided by the midwives.
      Mostly, women appreciated the midwives' expertise in providing maternity care.
      Majority of the women acknowledged the continuous presence of the midwives during
      childbirth and the women shared that they were empowered to make decisions
      related to their care. Most of the women indicated that marketing for MLC is
      scarce and insufficient. Majority of the women are even not aware of this model;
      therefore, it is imperative to create awareness and to provide MLC access to
      women through robust marketing. IMPLICATIONS FOR PRACTICE: the findings of this
      study may help to advocate and provide women-friendly maternity care, by giving
      choice and control to women during childbirth, providing comfort to women by
      using fewer medical interventions, and promoting normality by attending
      spontaneous vaginal childbirths.

PMID- 24290947
TI  - Establishing midwifery in low-resource settings: guidance from a mixed-methods
      evaluation of the Afghanistan midwifery education program.
AB  - BACKGROUND: The shortage of skilled birth attendants has been a key factor in the
      high maternal and newborn mortality in Afghanistan. Efforts to strengthen pre
      service midwifery education in Afghanistan have increased the number of midwives
      from 467 in 2002 to 2954 in 2010. OBJECTIVE: We analyzed the costs and graduate
      performance outcomes of the two types of pre-service midwifery education programs
      in Afghanistan that were either established or strengthened between 2002 and 2010
      to guide future program implementation and share lessons learned. DESIGN: We
      performed a mixed-methods evaluation of selected midwifery schools between June
      2008 and November 2010. This paper focuses on the evaluation's quantitative
      methods, which included (a) an assessment of a sample of midwifery school
      graduates (n=138) to measure their competencies in six clinical skills; (b)
      prospective documentation of the actual clinical practices of a subsample of
      these graduates (n=26); and (c) a costing analysis to estimate the resources
      required to educate students enrolled in these programs. SETTING: For the
      clinical competency assessment and clinical practices components, two Institutes
      for Health Sciences (IHS) schools and six Community Midwifery Education (CME)
      schools; for the costing analysis, a different set of nine schools (two IHS,
      seven CME), all of which were funded by the US Agency for International
      Development. PARTICIPANTS: Midwives who had graduated from either IHS or CME
      schools. FINDINGS: CME graduates (n=101) achieved an overall mean competency
      score of 63.2% (59.9-66.6%) on the clinical competency assessment compared to
      57.3% (49.9-64.7%) for IHS graduates (n=37). Reproductive health activities
      accounted for 76% of midwives' time over an average of three months.
      Approximately 1% of childbirths required referral or resulted in maternal death.
      On the basis of known costs for the programs, the estimated cost of graduating a
      class with 25 students averaged US$298,939, or US$10,784 per graduate. KEY
      CONCLUSIONS: The pre-service midwifery education experience of Afghanistan can
      serve as a model to rapidly increase the number of skilled birth attendants. In
      such settings, it is important to ensure the provision of continued practice
      opportunities and refresher trainings after graduation to aid skill retention, a
      co-operative and supportive work environment that will use midwives for the
      reproductive health skills for which they were trained, and selection mechanisms
      that can identify the most promising students and post-graduation deployment
      options to maximise the return on the substantial educational investment.

PMID- 24290948
TI  - Subcortical volume analysis in traumatic brain injury: the importance of the
      fronto-striato-thalamic circuit in task switching.
AB  - Traumatic brain injury (TBI) is associated with neuronal loss, diffuse axonal
      injury and executive dysfunction. Whereas executive dysfunction has traditionally
      been associated with prefrontal lesions, ample evidence suggests that those
      functions requiring behavioral flexibility critically depend on the interaction
      between frontal cortex, basal ganglia and thalamus. To test whether structural
      integrity of this fronto-striato-thalamic circuit can account for executive
      impairments in TBI we automatically segmented the thalamus, putamen and caudate
      of 25 patients and 21 healthy controls and obtained diffusion weighted images. We
      assessed components of executive function using the local-global task, which
      requires inhibition, updating and switching between actions. Shape analysis
      revealed localized atrophy of the limbic, executive and rostral-motor zones of
      the basal ganglia, whereas atrophy of the thalami was more global in TBI. This
      subcortical atrophy was related to white matter microstructural organization in
      TBI, suggesting that axonal injuries possibly contribute to subcortical volume
      loss. Global volume of the nuclei showed no clear relationship with task
      performance. However, the shape analysis revealed that participants with smaller
      volume of those subregions that have connections with the prefrontal cortex and
      rostral motor areas showed higher switch costs and mixing costs, and made more
      errors while switching. These results support the idea that flexible cognitive
      control over action depends on interactions within the fronto-striato-thalamic
      circuit. 

PMID- 24290949
TI  - The use of heterogeneous acellular dermal matrix in the closure of hard palatal
      fistula.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of closure of hard
      palatal fistula using Heal-All((r)) Oral Biofilm, a heterogeneous acellular
      dermal matrix graft. PATIENTS AND METHODS: Superior lip mucosal or myomucosal
      flap and buccal myomucosal flap were used in 20 patients (group 1) (2000-2005);
      whereas, heterogeneous acellular dermal matrix graft was performed in 18 patients
      (group 2) (2005-2013). The recurrence in the closed fistula and the obliteration
      of gingivolabial and gingivobuccal sulci were seen postoperatively with follow-up
      appointments at 1-3 months for all cases. RESULTS: The recurrence rate of hard
      palatal fistula has been reduced from 25 to 11.1% with the use of heterogeneous
      acellular dermal matrix graft, and the rate of the obliteration of gingivolabial
      and gingivobuccal sulci has been decreased from 90 to 5.5%. CONCLUSIONS: Closure
      of hard palatal fistula using Heal-All((r)) Oral Biofilm graft is a useful method
      with high success rate. It is a day-case procedure especially to avoid dividing
      the pedical of the flap after follow-up, and the gingivolabial and gingivobuccal
      sulci do not need further procedures to deep with follow-up.

PMID- 24290950
TI  - Auditory development after placement of bone-anchored hearing aids Softband among
      Chinese Mandarin-speaking children with bilateral aural atresia.
AB  - OBJECTIVE: To evaluate auditory developments of Chinese Mandarin-speaking
      children with congenital bilateral aural atresia after using Bone-anchored
      hearing aids (Baha) Softband and to compare them with matched peers with normal
      hearing. METHOD: Sixteen patients (age ranging from 3 months to 6 years) with
      bilateral aural atresia and 29 children with normal hearing (age ranging from 8
      months to 6 years) were studied. Auditory development was assessed at three time
      intervals: baseline, 6 months and 12 months. Infant-Toddler Meaningful Auditory
      Integration Scale (IT-MAIS) was conducted for children under 4 years old;
      Meaningful Auditory Integration Scale (MAIS), Chinese Mandarin lexical
      neighborhood test (MLNT) and sound field pure tone audiometry (PTA) were used for
      children of 4-6 years old. RESULTS: Mean IT-MAIS scores were 41 +/- 24%, 60 +/-
      22% and 73 +/- 7%, respectively at three time intervals. Mean MAIS scores were 66
      +/- 7%, 90 +/- 5%, and 99 +/- 2%. Mean speech discrimination scores at the three
      time intervals were 74 +/- 19%, 86 +/- 16%, and 95 +/- 4% with the easy
      disyllabic (D-E) list; 48 +/- 18%, 73 +/- 15%, and 81 +/- 7% with the hard
      disyllabic (D-H) list; 55 +/- 17%, 74 +/- 22%, and 83 +/- 14% with the easy
      monosyllabic(M-E) list; and 31 +/- 14%, 61 +/- 15%, and 71 +/- 13% with the hard
      monosyllabic (M-H) list. CONCLUSIONS: Baha Softband is suitable for infants and
      young children with bilateral atresia. Results from these auditory development
      testing are encouraging. Baha Softband should be used as a bridge for surgical
      implantations when the temporal bone is thick enough.

PMID- 24290951
TI  - Autism spectrum disorders in 24 children who are deaf or hard of hearing.
AB  - OBJECTIVES: Approximately 4% of children who are deaf or hard of hearing have co
      occurring autism spectrum disorder (ASD). Making an additional diagnosis of ASD
      in this population can be challenging, given the complexities of determining
      whether speech/language and social delays can be accounted for by their hearing
      loss, or whether these delays might be indicative of a comorbid ASD diagnosis.
      This exploratory study described a population of 24 children with the dual
      diagnosis of ASD and hearing loss. METHODS: Children completed a comprehensive
      ASD evaluation using standardized autism diagnostic instruments (Autism
      Diagnostic Observation Schedule, language and psychological testing). Children
      with permanent hearing loss who had a developmental evaluation between 2001 and
      2011 and were diagnosed with an ASD based on the results of that evaluation were
      included. Information on communication modality, language and cognitive abilities
      was collected. RESULTS: The median age of diagnosis was 14 months (range 1-71)
      for hearing loss and 66.5 months (range 33-106) for ASD. Only 25% (n=6) children
      were diagnosed with ASD <= 48 months of age and 46% by <= 6 years. Twelve (50%)
      children were diagnosed with ASD, 11 were diagnosed with pervasive developmental
      disorder not otherwise specified and 1 child had Asperger's. Most (67%) had
      profound degree of hearing loss. Fourteen (58%) children had received a cochlear
      implant, while 3 children had no amplification for hearing loss. Nine (38%) of
      the 24 children used speech as their mode of communication (oral communicators).
      CONCLUSIONS: Communication delays in children who are deaf or hard of hearing are
      a serious matter and should not be assumed to be a direct consequence of the
      hearing loss. Children who received cochlear implants completed a
      multidisciplinary evaluation including a developmental pediatrician, which may
      have provided closer monitoring of speech and language progression and
      subsequently an earlier ASD diagnosis. Because children who are deaf or hard of
      hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD
      at older ages.

PMID- 24290953
TI  - A rare cause of pediatric dysphagia: posterior dislocation of the
      sternoclavicular joint.
AB  - Rarely do orthopedic injuries in children present with dysphagia. Acute onset
      dysphagia after falling or getting tackled with subtle symptoms or unremarkable
      physical examination findings should raise suspicion for posterior dislocation of
      the sternoclavicular joint (SCJ). A case is described and used to highlight an
      uncommon cause of dysphagia in children. It can be easily missed because the
      presenting symptoms and physical examination findings are subtle. Standard
      radiographs are not sufficient for diagnosis, and a high degree of suspicion is
      necessary to pursue further diagnostic studies. Open reduction and internal
      fixation can be effective for improving their symptoms, often immediately
      postoperatively.

PMID- 24290952
TI  - Aggressive fibromatosis of the head and neck in the pediatric population.
AB  - BACKGROUND: Aggressive fibromatosis, previously referred to as desmoid tumor, is
      a rare tumor. It is classified as benign, however, has a high potential for local
      invasion and recurrence. It is most commonly found in the abdomen, with an origin
      in the head and neck accounting for less than a quarter of the total cases.
      METHODS: Literature review using PubMed and OVID and a combination of the words,
      "desmoid", "fibromatosis", "pediatric", "children", and "head and neck". RESULTS:
      Annual occurrence is 0.2 - 0.4 per 100,000, with origins in the head and neck
      accounting for 10-25%. Since 1954, 97 cases of pediatric head and neck
      fibromatosis were reported. The age range was from birth to 16 years, with the
      average being 4 years and 5 months old. The overwhelming majority of tumors were
      of the mandible (38%). 74% patients underwent a large resection as the primary
      treatment modality. The most common treatment complication was tumor recurrence
      (16%). CONCLUSIONS: Fibromatosis is a rare tumor of muscoloaponeurotic origin.
      Surgery is the mainstay of treatment; however recurrence rates are high, even
      despite negative surgical margins.

PMID- 24290954
TI  - Pharyngeal perforation after blunt cervical trauma in child.
AB  - Pharyngeal perforation caused by non-penetrating cervical trauma is an extremely
      rare clinical entity both in adults and children. Data concerning management of
      this type of injury are quite rare in surgical and even scarcer in pediatric
      literature. Since delay in treatment may be associated with life-threatening
      complications, prompt diagnosis coupled with appropriate therapy is essential for
      achieving favorable clinical outcome. To the best of authors' knowledge, the
      present study illustrates for the first time the experience with successful
      treatment of pharyngeal perforation caused by a blunt cervical trauma in a child.

PMID- 24290955
TI  - EarigateTM for softening ear wax: is it safe when the eardrum is perforated?
AB  - OBJECTIVE: To determine the safety of EarigateTM as an ear wax softening product.
      STUDY DESIGN: Prospective, controlled animal study. METHODS: Bilateral wide
      myringotomies were performed in eleven chinchillas. In each animal, EarigateTM
      was delivered to a randomly selected experimental ear canal as 2 puffs twice a
      day. Auditory brainstem response (ABR) was used to assess the hearing of the
      animals before, 3 days and 10 days following the local application of EarigateTM.
      The ABR threshold shifts were compared for both experimental and control ears.
      RESULTS: The mean hearing threshold shifts in the experimental animals were
      comparable at all frequencies and at days 3 and 10. No statistically significant
      differences were observed in the mean threshold shifts for all of the frequencies
      evaluated, between the control and experimental ears. CONCLUSIONS: The
      administration of EarigateTM to the middle ear of chinchillas did not cause any
      ototoxicity as assessed by ABR.

PMID- 24290956
TI  - Demonstration of the role of an implantable bioscaffold in airway reconstruction:
      a pilot study utilizing an animal model.
AB  - INTRODUCTION: Laryngotracheal reconstruction is a common procedure to repair
      subglottic stenosis. Despite a success rate upwards of 85%, this procedure has
      significant morbidity associated with it, specifically with the site of the graft
      harvest and recurrence of stenosis. We propose that a recently described cellular
      bioscaffold xenograft may be useful in reducing these complications. METHODS AND
      MATERIALS: 10 Sprague Dawley rats were divided into 2 groups of 5. One group
      underwent incision through the cricoid and the first two tracheal rings followed
      by primary closure (G1); the second group underwent incision through the cricoid
      and the first two tracheal rings followed by placement of the xenograft (G2);
      additionally, a specimen was harvested from an animal which did not undergo any
      surgical procedure to compare to the two surgical groups. Specimen harvest
      occurred on post-operative days 1, 7, 14, 21, and 28. RESULTS: 6 of 10 animals
      provided usable data. All animals receiving the xenograft survived until the time
      of specimen harvest. Only 1 animal undergoing primary closure survived beyond
      post-operative day one. On histology review, the xenograft animals showed a
      progressive decrease in fibrosis relative to the animals that underwent primary
      closure. On POD 28, restoration of the respiratory epithelium and intact basement
      membrane was noted in the xenograft group. CONCLUSION: We believe that this pilot
      study shows the potential of utilizing bio-implantable biomaterials, specifically
      a cellular bioscaffold which encourages the ingrowth of native tissue instead of
      fibrosis. Histologic analysis shows that use of the xenograft can initiate the
      proliferation of native tissues decreasing the amount of fibrosis present post
      operatively, although significant further analysis is needed before definitively
      concluding that this approach is superior to utilization of a graft.

PMID- 24290957
TI  - Approximate nearest neighbour field based optic disk detection.
AB  - Approximate Nearest Neighbour Field maps are commonly used by computer vision and
      graphics community to deal with problems like image completion, retargetting,
      denoising, etc. In this paper, we extend the scope of usage of ANNF maps to
      medical image analysis, more specifically to optic disk detection in retinal
      images. In the analysis of retinal images, optic disk detection plays an
      important role since it simplifies the segmentation of optic disk and other
      retinal structures. The proposed approach uses FeatureMatch, an ANNF algorithm,
      to find the correspondence between a chosen optic disk reference image and any
      given query image. This correspondence provides a distribution of patches in the
      query image that are closest to patches in the reference image. The likelihood
      map obtained from the distribution of patches in query image is used for optic
      disk detection. The proposed approach is evaluated on five publicly available
      DIARETDB0, DIARETDB1, DRIVE, STARE and MESSIDOR databases, with total of 1540
      images. We show, experimentally, that our proposed approach achieves an average
      detection accuracy of 99% and an average computation time of 0.2 s per image.

PMID- 24290958
TI  - Research opportunities for vascular endothelial growth factor receptor and Ki67
      relative percentage co-reduction in patients with locally advanced rectal cancer
      treated with neoadjuvant therapy.

PMID- 24290959
TI  - Genistein induces morphology change and G2/M cell cycle arrest by inducing p38
      MAPK activation in macrophages.
AB  - Genistein is a well known natural compound which is present in soy foods and
      exerts many beneficial functions such as anticancer, anti-inflammatory and
      antioxidant. However, until now little is known about the effects of genistein on
      the function of macrophages. The murine macrophage cell line RAW264.7 was used as
      target cell line. The results show that at concentrations of 50-100MUM, genistein
      reduced cell viability to 70%-80% (after 24h) and 50%-60% (after 48h), which was
      due to G2/M phase cell cycle arrest. Treatment of the macrophages with genistein
      for 24 or 48h also led to significant morphological changes, such as elongation
      of the cells and development of long pseudopodia-like protrusions. By staining
      the F-actin cytoskeleton, we observed accumulation of actin-filaments at the
      edges of the cells. The morphology change and G2/M phase arrest after genistein
      treatment is due to the activation of the phosphorylation of MAP kinase p38. The
      morphology change and cell cycle arrest can be significantly reverted when
      treatment is combined with p38 inhibitor SB203580. Moreover, after treatment of
      the macrophages with genistein for 24 and 48h, the phagocytotic efficiency for
      Candida albicans was decreased in a time- and dose-dependent manner which
      correlates to the morphology change. The production of cytokines (TNF-alpha)
      stimulated by C. albicans was strongly inhibited by genistein. In conclusion,
      genistein showed a strong immune modulatory effect on the macrophages. 

PMID- 24290960
TI  - Correlation between circulating proteasome activity, total protein and c-reactive
      protein levels following burn in children.
AB  - AIM OF THE STUDY: To characterize burn-induced changes following burn in children
      by analyzing circulating proteasome (c-proteasome) activity in the plasma in
      correlation with total protein and c-reactive protein levels in the plasma, and
      the severity of the burn. METHODS: Fifty consecutive children scalded by hot
      water who were managed at the Department of Pediatric Surgery after primarily
      presenting with burns in 4-20% TBSA were included into the study. The children
      were aged 9 months up to 14 years (mean age 2.5+/-1 years). Patients were divided
      into groups according to the pediatric injury severity score used by American
      Burns Association. Plasma proteasome activity was assessed using Suc-Leu-Leu-Val
      Tyr-AMC peptide substrate, 2-6 h, 12-16 h, 3 days, 5 days, and 7 days after
      injury. 20 healthy children consecutively admitted for planned inguinal hernia
      repair served as controls. RESULTS: Statistically significant elevation of plasma
      c-proteasome activity was noted in all groups of burned children 12-16 h after
      the injury. We found a strong negative correlation of c-proteasome activity with
      total protein levels, and positive correlation with CRP levels 12-16 h after
      burn. We also found stronger correlation between c-proteasome activity and
      severity of burn, than CRP level and severity of burn 12-16 h, and 3 days after
      the burn. Correlations were statistically significant. CONCLUSIONS: This study
      characterized circulating 20S proteasome activity levels after burn. C-proteasome
      activity elevate after burn and correlate negatively with plasma total protein
      level, thus plasma 20S proteasome activity could be additional biomarker of
      tissue damage in burn in pediatric population.

PMID- 24290961
TI  - The antibacterial activity of geranium oil against Gram-negative bacteria
      isolated from difficult-to-heal wounds.
AB  - Hard-to-heal wounds represent a significant problem to patients, health care
      professionals, and health care system. They can be formed as a result of
      mechanical injuries and burns, and any co-existing chronic disease increases the
      risk of their emergence. Diabetics are at a greater risk of developing chronic
      wounds because of poor circulation, slow healing times, vascular disease and
      neuropathy. The aim of this study was to determine the antimicrobial activity of
      geranium oil against Gram-negative bacterial clinical strains. Clinical strains
      were isolated from patients with difficult-to-treat wounds and a comprehensive
      evaluation of their sensitivity to antibiotics was carried out. The constituents
      of geranium oil were specified by GC-FID-MS analysis. The micro-dilution broth
      method was used to check the inhibition of microbial growth at various
      concentrations of geranium oil. The tested geranium oil was efficacious against
      Gram-negative pathogens responsible for problems with wound treatment. The
      results suggest that geranium oil may be considered an effective component of
      therapy in the case of frequent recurrences of infections caused by resistant
      pathogens. 

PMID- 24290962
TI  - Probiotics, gut microbiota and health.
AB  - The human gut is a huge complex ecosystem where microbiota, nutrients, and host
      cells interact extensively, a process crucial for the gut homeostasis and host
      development with a real partnership. The various bacterial communities that make
      up the gut microbiota have many functions including metabolic, barrier effect,
      and trophic functions. Hence, any dysbiosis could have negative consequences in
      terms of health and many diseases have been associated to impairment of the gut
      microbiota. These close relationships between gut microbiota, health, and
      disease, have led to great interest in using probiotics (i.e. live micro
      organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate
      the gut microbiota to prevent or treat some diseases. This review focuses on
      probiotics, their mechanisms of action, safety, and major health benefits. Health
      benefits remain to be proven in some indications, and further studies on the best
      strain(s), dose, and algorithm of administration to be used are needed.
      Nevertheless, probiotic administration seems to have a great potential in terms
      of health that justifies more research. 

PMID- 24290963
TI  - [Vasoactive intestinal peptide-secreting ganglioneuroblastoma in a 20 month-old
      child].

PMID- 24290964
TI  - [Glycemic variability and oxidative stress in children, with type 1 diabetes
      attending a summer camp].
AB  - OBJECTIVE: To assess glycemic variability, oxidative stress and their
      relationship in children and adolescents with type 1 diabetes (T1DM) attending a
      summer camp. PATIENTS AND METHOD: Cross-sectional study that included 54 children
      and adolescents with T1DM aged 7-16, attending a 7 day summer camp.
      Sociodemographic information, clinical data, and blood glucose values measured
      using an Accu-Chek Nano(r) glucose meter were recorded. Glucose variability
      markers (standard deviation [SD], low blood glucose index [LBGI], high blood
      glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of
      daily differences [MODD]) were calculated. Oxidative stress was assessed by the
      measurement of 8-iso-prostaglandin F2 alpha (PGF2alpha) in a 24-hour urine sample
      collected at the end of the camp in 14 children. RESULTS: The Median SD, MAGE and
      MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in
      the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was
      7.6% and the median urinary excretion rate of 8-iso-PGF2alpha was 864.39 pg/mg
      creatinine. The Spearman correlation coefficients between markers of glycemic
      variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations
      were found between markers of glycemic variability and urinary 8-iso-PGF2alpha.
      CONCLUSIONS: High glycemic variability was observed in children and adolescents
      attending a summer camp. However, no correlations were found between markers of
      glycemic variability and oxidative stress measured by urinary 8-iso-PGF2alpha.
      Further studies are needed to address the relationship between oxidative stress
      and glycemic variability in children with T1DM.

PMID- 24290965
TI  - [First onset of diplopia and descending paralysis: atypical Guillain-Barre].

PMID- 24290966
TI  - [Homeopathic products: the importance of correct information].

PMID- 24290967
TI  - Early operative intervention is associated with better patient survival in
      patients with intracapsular femur fractures but not extracapsular fractures.
AB  - The purpose of this study was to determine patients' survival after undergoing an
      early or delayed operation. We retrospectively assessed 1849 files of patients
      operated for proximal femoral fracture, divided into two diagnostic groups:
      intracapsular (n = 640) and extracapsular (n = 1209). 1163 (63%) were treated
      within 48 h from hospital admission and 686 (37%) were treated >48 h afterwards.
      Delayed operation in patients with intracapsular fractures was associated with a
      1.8-fold excess risk for 1-year mortality (HR = 1.83, P = 0.008), while no effect
      was observed for patients with extracapsular fractures. Males had a higher HR for
      mortality in both diagnostic groups. Early surgical intervention is beneficial
      for intra-capsular femoral fractures; male gender and a high ASA score are
      associated with an increased mortality hazard risk.

PMID- 24290968
TI  - Changes in blood coagulation-fibrinolysis markers by pneumatic tourniquet during
      total knee joint arthroplasty with venous thromboembolism.
AB  - This study investigated changes in blood coagulation-fibrinolysis markers during
      total knee arthroplasty (TKA). Preoperative 16-row multidetector row computed
      tomography (MDCT) revealed no asymptomatic venous thromboembolism (VTE) in the 42
      patients recruited. Using MDCT postoperatively, patients were divided into
      thrombus (asymptomatic VTE, 19 patients) and no-thrombus (23 patients) groups.
      Blood taken at intervals before and after pneumatic tourniquet release revealed
      increased plasminogen activator inhibitor type-1 (PAI-1) at 30s for both groups
      and at 90s (both P=0.01) in the thrombus group. D-dimer levels were highest at 30
      and 90s for both groups (P = 0.01). PAI-1 and D-dimer levels were strongly
      correlated at both time points in the thrombus group. Inactivating fibrinolysis
      due to PAI-1 may lead to asymptomatic VTE after TKA.

PMID- 24290969
TI  - Optimization of micro-aeration intensity in acidogenic reactor of a two-phase
      anaerobic digester treating food waste.
AB  - Micro-aeration is known to promote the activities of hydrolytic exo-enzymes and
      used as a strategy to improve the hydrolysis of particulate substrate. The effect
      of different micro-aeration rates, 0, 129, 258, and 387 L-air/kg TS/d (denoted as
      LBR-AN, LBR-6h, LBR-3h and LBR-2h, respectively) on the solubilization of food
      waste was evaluated at 35 degrees C in four leach bed reactors (LBR) coupled with
      methanogenic upflow anaerobic sludge blanket (UASB) reactor. Results indicate
      that the intensity of micro-aeration influenced the hydrolysis and methane yield.
      Adequate micro-aeration intensity in LBR-3h and LBR-2h significantly enhanced the
      carbohydrate and protein hydrolysis by 21-27% and 38-64% respectively. Due to the
      accelerated acidogenesis, more than 3-fold of acetic acid and butyric acid were
      produced in LBR-3h as compared to the anaerobic treatment LBR-AN resulting in the
      maximum methane yield of 0.27 L CH4/g VS(added) in the UASB. The performance of
      LBR-6h with inadequate aeration was similar to that of LBR-AN with a comparable
      hydrolysis degree. Nevertheless, higher aeration intensity in LBR-2h was also
      unfavorable for methane yield due to significant biomass generation and CO2
      respiration of up to 18.5% and 32.8% of the total soluble hydrolysate,
      respectively. To conclude, appropriate micro-aeration rate can promote the
      hydrolysis of solid organic waste and methane yield without undesirable carbon
      loss and an aeration intensity of 258 L-air/kg TS/d is recommended for acidogenic
      LBR treating food waste.

PMID- 24290970
TI  - Evaluation of laboratory-scale in-vessel co-composting of tobacco and apple
      waste.
AB  - Efficient composting process requires set of adequate parameters among which
      physical-chemical properties of the composting substrate play the key-role.
      Combining different types of biodegradable solid waste it is possible to obtain a
      substrate eligible to microorganisms in the composting process. In this work the
      composting of apple and tobacco solid waste mixture (1:7, dry weight) was
      explored. The aim of the work was to investigate an efficiency of biodegradation
      of the given mixture and to characterize incurred raw compost. Composting was
      conducted in 24 L thermally insulated column reactor at airflow rate of 1.1 L
      min(-1). During 22 days several parameters were closely monitored: temperature
      and mass of the substrate, volatile solids content, C/N ratio and pH-value of the
      mixture and oxygen consumption. The composting of the apple and tobacco waste
      resulted with high degradation of the volatile solids (53.1%). During the
      experiment 1.76 kg of oxygen was consumed and the C/N ratio of the product was
      11.6. The obtained temperature curve was almost a "mirror image" of the oxygen
      concentration curve while the peak values of the temperature were occurred 9.5h
      after the peak oxygen consumption.

PMID- 24290971
TI  - Comparative assessment of municipal sewage sludge incineration, gasification and
      pyrolysis for a sustainable sludge-to-energy management in Greece.
AB  - For a sustainable municipal sewage sludge management, not only the available
      technology, but also other parameters, such as policy regulations and socio
      economic issues should be taken in account. In this study, the current status of
      both European and Greek Legislation on waste management, with a special insight
      in municipal sewage sludge, is presented. A SWOT analysis was further developed
      for comparison of pyrolysis with incineration and gasification and results are
      presented. Pyrolysis seems to be the optimal thermochemical treatment option
      compared to incineration and gasification. Sewage sludge pyrolysis is favorable
      for energy savings, material recovery and high added materials production,
      providing a 'zero waste' solution. Finally, identification of challenges and
      barriers for sewage sludge pyrolysis deployment in Greece was investigated. 

PMID- 24290972
TI  - Complementary innate (anti-A-specific) IgM emerging from ontogenic O-GalNAc
      transferase depletion: (Innate IgM complementarity residing in ancestral antigen
      completeness).
AB  - The murine and the human genome have global properties in common. So the murine
      anti-A-specific complementary IgM and related human innate isoagglutinin
      represent developmental, 2-mercaptoethanol-sensitive, complement-binding
      glycoproteins, which do not arise from any measurable environmentally-induced or
      auto- immune response. The murine anti-A certainly originates from a cell surface
      or cell adhesion molecule, which in the course of germ cell development becomes
      devoid of O-GalNAc-transferase and is released into the circulation. In human
      sera the enzyme occurs exclusively in those of blood group A- and AB subjects,
      while in group O(H) an identically encoded protein lets expect an opposite
      function and appears in conjunction with a complementary anti-A reactive
      glycoprotein. Since O-glycosylations rule the carbohydrate metabolism in growth
      and reproduction processes, we propose that the ancestral histo-(blood)-group A
      molecule arises in the course of O-GalNAc-glycosylations of glycolipids and
      protein envelops at progenitor cell surfaces. Germ cell development postulates
      embryonic stem cell fidelity, which is characterised by persistent production of
      alpha-linked O-GalNAc-glycans. They are determined by the A-allele within the
      human, "complete" histo (blood) group AB(O) structure that in early ontogeny is
      hypothesised to be synthesised independently from the final phenotype. The
      structure either passes "completely" through the germline, in transferase
      secreting mature tissues becoming the "complete" phenotype AB, or disappears in
      exhaustive glycotransferase depletion from the differentiating cell surfaces and
      leaves behind the "incomplete" blood group O-phenotype, which has released a
      transferase- and O-glycan-depleted, complementary glycoprotein (IgM) into the
      circulation. The process implies, that in humans the different blood phenotypes
      evolve from a "complete" AB(O) molecular complex in a distinct enzymatic and/or
      complement cascade suggesting O-glycanase involvements. While the murine and
      human oocyte zona pellucida express identical O-glycans, the human phenotype O
      might be explainable by the kinetics of the murine ovarian O-GalNAc glycan
      synthesis and the complementary anti-A released in parallel. The maturing murine
      ovary may provide insight into encoding of the physiologically superior alpha
      linked GalNAc ancestral epitope that becomes essential in reproduction as well as
      in tissue renewal events. According to recent reports, O-GalNAc-transferase
      determined blood group A suggests superiority in human female fertility and was
      called even "protective". So the minor fertility of blood-group-O females may
      reside in a critical timing in developmental shifting of enzyme functions
      affecting the formation of GalNAc-determined hormone receptors on the way to
      maturation. Experiments that had inserted an oocyte genome into a somatic one to
      generate pluripotent stem cells, might elucidate a developmental dilemma by
      testing oocytes from different blood group AB donors donors. Perhaps they will
      unmask the molecular basis of an evolutionary trend, while stem cell generation
      itself capitalises on the enzymatically-advantaged, lineage-maintaining (histo)
      blood group A-allele, which guaranties ancestral functional completeness.

PMID- 24290973
TI  - Comparative mucosal immunogenicity of HIV gp41 membrane-proximal external region
      (MPER) containing single and multiple repeats of ELDKWA sequence with defensin
      peptides.
AB  - The MPER of gp41 of HIV-1 has received great attention and is widely recognized
      as a promising target for the development of AIDS vaccine. We investigated the
      ability of trirepeat of ELDKWA sequence of gp41 antigen with defensins in
      liposome using multiple-shot immunization strategy in the mice model. The
      designed was used to enhance the immunogenicity and exposure of MPER in its
      native conformation for the induction of MPER-specific HIV-1 neutralizing
      antibodies. To characterize, we estimated the antibody levels (IgG/IgA) in serum
      as well as in lung, intestinal, vaginal and rectal washes till day 120 in outbred
      and inbred (H-2(b) and H-2(d)) mice using liposome as delivery vehicle. The
      representative sera and washes were also tested for in vitro neutralization with
      CCR5-tropic Indian HIV-1 primary isolates. We observed that the modified HIV
      antigen containing trirepeat of ELDKWA with defensins was showing significantly
      (p<0.001) higher IgG/IgA antibody titre (102,400-204,800) in sera as well as in
      different mucosal washes (1600-6400) than standard HIV-1 antigen. Furthermore,
      sera from the modified HIV-1 antigen with defensins found to exhibit higher
      neutralizing activities (ranging from 59.3% to 84.6%) than the standard HIV-1
      antigen. These results show that the induction of MPER-specific HIV-1
      neutralizing antibodies could be achieved through a rationally designed vaccine
      strategy.

PMID- 24290974
TI  - Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and
      fluorescence imaging with a dansyl analogue.
AB  - The diethyl ester of [(18)F]ML-10 is a small molecule apoptotic PET probe for
      cancer studies. Here we report a novel multi-step synthesis of the diethyl ester
      of ML-10 in excellent yields via fluorination using Xtal-Fluor-E. In addition, a
      one-pot radiosynthesis of the diethyl ester of [(18)F]ML-10 from nucleophilic
      [(18)F]fluoride was completed in 23% radiochemical yield (decay corrected). The
      radiochemical purity of the product was >=99%. The diethyl ester of [(18)F]ML-10
      was used in vivo to detect apoptosis in the testes of mice. In parallel studies,
      the dansyl-ML-10 diethyl ester was prepared and used to detect apoptotic cells in
      an in vitro cell based assay.

PMID- 24290975
TI  - Appearance of regressing Drusen on adaptive optics in age-related macular
      degeneration.

PMID- 24290976
TI  - A novel pre-surgical maxillary orthodontic device using beta-titanium wire for
      wide unilateral cleft lip and palate patients: preliminary study of its efficacy
      and impact for the maxillary formation.
AB  - BACKGROUND AND AIM: For patients with a wide, complete, unilateral cleft lip and
      palate, pre-surgical maxillary orthodontic treatments have been used to reduce
      the alveolar gap before cheiloplasty. However, most of these treatments are
      complicated and laborious for patients and for medical professionals. Thus, we
      developed an original pre-surgical orthodontic device made with two separate
      acrylic resin plates connected with a spring-shaped beta-titanium wire (beta-TW).
      When the device was applied on the palate, each segment of the maxilla was
      automatically aligned for our target formation with the elastic force of beta
      titanium alloy. This study aimed to evaluate the efficacy of the new device and
      the size of the maxilla in comparison with the conventional Hotz procedures.
      PATIENTS AND METHODS: A total of 47 patients with a wide unilateral cleft lip and
      palate were retrospectively evaluated; 33 patients were treated with our new
      device (beta-TW plate group) and 14 were treated with a Hotz plate (HP group). We
      evaluated the alveolar gap reduction and the size of the maxilla between the two
      groups, obtaining intraoral maxillary impressions at birth, at 3 months and 1
      year. RESULTS: The width of the alveolar gap in the beta-TW plate group was
      significantly reduced compared with that in the HP group 1 month after the
      treatment (p < 0.001). The alveolar gap reduction continued until the age of 1
      year (p = 0.02). By contrast, no significant difference in the maxillary size was
      observed between the two groups at any examination period. CONCLUSION: Our
      treatment protocol using the beta-TW plate was not only easy and simple to apply
      but it was also cost-effective, with highly predictable outcomes. Moreover, it
      provided the ideal alveolar cleft reduction without detrimental collapse of the
      alveolar segments. Therefore, we consider our beta-TW plate device to be useful
      for application in pre-surgical orthodontic treatments.

PMID- 24290977
TI  - Comparative analysis between minimal access versus traditional accesses in carpal
      tunnel syndrome: a perspective randomised study.
AB  - INTRODUCTION: Carpal tunnel decompression with division of the transverse carpal
      ligament has been a highly successful procedure for the treatment of carpal
      tunnel syndrome. The standard longitudinal incision technique, with a long
      curvilinear incision, has been the optimal treatment procedure for surgical
      decompression of the median nerve, for many surgeons. The aim of this study was
      to compare the traditional open carpal tunnel release (TOCTR) technique with the
      minimal-access carpal tunnel release (MACTR) technique for the treatment of
      carpal tunnel syndrome (CTS), presenting our experience. MATERIALS AND METHODS: A
      total of 120 patients eligible for carpal tunnel decompression were recruited
      into the study. The patients were randomised for treatment allocation, at a 1:1
      ratio, resulting in 60 patients in group A, treated by standard TOCTR, and 60
      patients in group B, treated by MACTR. To evaluate patients' outcomes we used the
      Boston Carpal Tunnel (BCT) questionnaire; the formed scar was evaluated according
      to the Vancouver scale and short- and long-term complications. Statistical
      analysis was performed by the chi-squared test and analysis of variance (ANOVA);
      Excel was the program used. RESULTS: In our series, there was no complication
      related to the surgical intervention of any injury to nerve, artery or tendon
      structures. In each section of the BCT questionnaire, patients in group B had
      significantly better results than patients in group A at both 6 and 12 months'
      follow-up (p < 0.001). For the Vancouver scar scale, there was a significant
      difference between two groups' scores; group B patients had significant
      improvements compared with group A patients. CONCLUSIONS: In our perspective
      randomised study, MACTR showed statistically significant improvement compared to
      TOCTR. The patient tolerance is reasonably high and the procedure is compatible
      with the current minimal invasive trend in surgery.

PMID- 24290978
TI  - Hot or not? The 10% rule in sentinel lymph node biopsy for malignant melanoma
      revisited.
AB  - BACKGROUND: The surgeon needs a practical rule to follow when deciding whether to
      excise a lymph node during sentinel node biopsy (SLNB). The "10% rule" dictates
      that all nodes with a radiation count of greater than 10% of the hottest node and
      all blue nodes should be removed, and this study observes the effects of
      following this rule in SLNB in melanoma. METHODS: We reviewed the records of 665
      patients with primary melanoma who underwent sentinel lymph node over a 5-year
      period (2007-2011). RESULTS: 2064 nodes were identified in 898 nodal basins in
      665 patients. 141 (21%) patients had at least one positive sentinel node. 105
      positive nodal basins were identified in which more than one sentinel node was
      removed. In 18 of these, a less radioactive node was positive for tumour when the
      most radioactive node was negative. Of 175 positive nodes 157 (90%) contained
      blue dye staining. For cases in which the positive sentinel node was not the
      hottest node, the positive node had apparent blue dye staining in all 18 cases
      (100%), and was the second hottest node in the basin. CONCLUSION: In this series
      removing just the hottest node and all blue nodes would not have missed a single
      positive basin and would have resulted in a 38% reduction in the number of nodes
      removed compared to those taken following the 10% rule, without changing the
      staging in any patient.

PMID- 24290979
TI  - Neonatal outcomes and their relationship to maternal buprenorphine dose during
      pregnancy.
AB  - BACKGROUND: Buprenorphine pharmacotherapy for opioid-dependent pregnant women is
      associated with maternal and neonatal outcomes superior to untreated opioid
      dependence. However, the literature is inconsistent regarding the possible
      existence of a dose-response relationship between maternal buprenorphine dose and
      neonatal clinical outcomes. METHODS: The present secondary analysis study (1)
      examined the relationship between maternal buprenorphine dose at delivery and
      neonatal abstinence syndrome (NAS) peak score, estimated gestational age at
      delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and
      weight at birth, amount of morphine needed to treat NAS, duration of NAS
      treatment, and duration of neonatal hospital stay and (2) compared neonates who
      required pharmacotherapy for NAS to neonates who did not require such
      pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women
      receiving buprenorphine as participants in a randomized clinical trial. RESULTS:
      (1) Analyses failed to provide evidence of a relationship between maternal
      buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and
      (2) significant mean differences between the untreated (n=31) and treated (n=27)
      for NAS groups were found for duration of neonatal hospital stay and NAS peak
      score (both p-values<.001). CONCLUSIONS: (1) Findings failed to support the
      existence of a dose-response relationship between maternal buprenorphine dose at
      delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2)
      that infants treated for NAS had a higher mean NAS peak score and, spent a longer
      time in the hospital than did the group not treated for NAS is unsurprising.

PMID- 24290980
TI  - Sensory-neuron subtype-specific transcriptional programs controlling dendrite
      morphogenesis: genome-wide analysis of Abrupt and Knot/Collier.
AB  - The transcription factors Abrupt (Ab) and Knot (Kn) act as selectors of distinct
      dendritic arbor morphologies in two classes of Drosophila sensory neurons, termed
      class I and class IV, respectively. We performed binding-site mapping and
      transcriptional profiling of these isolated neurons. Their profiles were
      similarly enriched in cell-type-specific enhancers of genes implicated in neural
      development. We identified a total of 429 target genes, of which 56 were common
      to Ab and Kn; these targets included genes necessary to shape dendritic arbors in
      either or both of the two sensory subtypes. Furthermore, a common target gene,
      encoding the cell adhesion molecule Ten-m, was expressed more strongly in class I
      than class IV, and this differential was critical to the class-selective
      directional control of dendritic branch sprouting or extension. Our analyses
      illustrate how differentiating neurons employ distinct and shared repertoires of
      gene expression to produce class-selective morphological traits.

PMID- 24290981
TI  - Control of epithelial cell migration and invasion by the IKKbeta- and CK1alpha
      mediated degradation of RAPGEF2.
AB  - Epithelial cell migration is crucial for the development and regeneration of
      epithelial tissues. Aberrant regulation of epithelial cell migration has a major
      role in pathological processes such as the development of cancer metastasis and
      tissue fibrosis. Here, we report that in response to factors that promote cell
      motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I
      kappa-B-kinase-beta and casein kinase-1alpha and consequently degraded by the
      proteasome via the SCF(betaTrCP) ubiquitin ligase. Failure to degrade RAPGEF2 in
      epithelial cells results in sustained activity of Rap1 and inhibition of cell
      migration induced by HGF, a potent metastatic factor. Furthermore, expression of
      a degradation-resistant RAPGEF2 mutant greatly suppresses dissemination and
      metastasis of human breast cancer cells. These findings reveal a molecular
      mechanism regulating migration and invasion of epithelial cells and establish a
      key direct link between IKKbeta and cell motility controlled by Rap-integrin
      signaling.

PMID- 24290982
TI  - The antitumor drug F14512 enhances cisplatin and ionizing radiation effects in
      head and neck squamous carcinoma cell lines.
AB  - BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most
      common cancer worldwide. The treatment of advanced stages HNSCC is based on
      surgical treatment combined with radiotherapy and chemotherapy or concomitant
      chemo-radiotherapy. However, the 5-year survival remains poor for advanced stages
      HNSCC and the development of new targeted therapies is eagerly awaited. F14512
      combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine
      moiety introduced as a cell delivery vector. This spermine moiety facilitates
      selective uptake by tumor cells via the Polyamine Transport System (PTS) and
      reinforces topoisomerase II poisoning. Here we report the evaluation of F14512
      toward HNSCC. MATERIALS AND METHODS: Four cell lines representative of head and
      neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and
      CAL27 (base of the tongue). PTS activity and specificity were evaluated by
      confocal microscopy and flow cytometry using the fluorescent probe F17073 which
      contains the same spermine moiety as F14512. Cytotoxicity, alone or in
      association with standard chemotherapeutic agents (cisplatin, 5FU), and radio
      sensitizing effects were investigated using MTS and clonogenic assays,
      respectively. F14512 efficiency and PTS activity were also measured under hypoxic
      conditions (1% O2). RESULTS: In all 4 tested HNSCC lines, an active PTS was
      evidenced providing a specific and rapid transfer of spermine-coupled compounds
      into cell nuclei. Interestingly, F14512 presents a 1.6-11-fold higher cytotoxic
      effect than the reference compound etoposide (lacking the spermine chain). It
      appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition
      experiments with spermine confirmed the essential role of the PTS in the cell
      uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug
      cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to
      be synergistic and, for the first time, we demonstrated the significant radio
      sensitizing potential of F14512. CONCLUSION: The spermine moiety of F14512
      confers a targeted effect and a much better efficacy than etoposide in HNSCC
      lines. The synergistic effect observed in association with cisplatin and
      radiotherapy augurs well for the potential development of F14512 in HNSCC.

PMID- 24290984
TI  - Journal update: what's new for 2014.

PMID- 24290983
TI  - Electromyographic analysis of upper limb muscles during standardized isotonic and
      isokinetic robotic exercise of spastic elbow in patients with stroke.
AB  - Although it has been reported that strengthening exercise in stroke patients is
      beneficial for their motor recovery, there is little evidence about which
      exercise method is the better option. The purpose of this study was to compare
      isotonic and isokinetic exercise by surface electromyography (EMG) analysis using
      standardized methods. Nine stroke patients performed three sets of isotonic elbow
      extensions at 30% of their maximal voluntary isometric torque followed by three
      sets of maximal isokinetic elbow extensions with standardization of mean angular
      velocity and the total amount of work for each matched set in two strengthening
      modes. All exercises were done by using 1-DoF planner robot to regulate exact
      resistive torque and speed. Surface electromyographic activity of eight muscles
      in the hemiplegic shoulder and elbow was recorded. Normalized root mean square
      (RMS) values and co-contraction index (CCI) were used for the analysis. The
      isokinetic mode was shown to activate the agonists of elbow extension more
      efficiently than the isotonic mode (normalized RMS for pooled triceps: 96.0+/
      17.0 (2nd), 87.8+/-14.4 (3rd) in isokinetic, 80.9+/-11.0 (2nd), 81.6+/-12.4 (3rd)
      in isotonic contraction, F[1,8]=11.168; P=0.010) without increasing the co
      contraction of muscle pairs, implicating spasticity or synergy. 

PMID- 24290985
TI  - Interview with Dan Mishell by Carole Joffe.

PMID- 24290986
TI  - Complex health care decisions for skilled nursing facilities and their residents:
      a discussion of recent Centers for Medicare and Medicaid services updates to
      survey and certification interpretive guidelines for feeding tubes and advance
      directives.

PMID- 24290987
TI  - Ethnography of health for social change: impact on public perception and policy.

PMID- 24290988
TI  - Swellings of the angle of the mandible in 32 horses (1997-2011).
AB  - Disorders of the horizontal ramus (body) of the equine mandible are well
      reported, but there is minimal documentation of disorders of the angle of
      mandible. A retrospective examination of the records of Edinburgh University
      Equine Hospital (1997-2011) showed that 32 horses were referred due to swellings
      of the angle of the mandible. The aetiology of these swellings was identified in
      just 13/32 cases (41%) including fractures (n=2), traumatic, localised
      periosteal/cortical lesions (n=4), traumatic soft tissue lesions (n=2), neoplasia
      (n=3), and inflammation of the adjacent salivary gland (n=1) and masseter muscle
      (n=1). The remaining 19 (59%) cases without a definitive diagnosis showed two
      patterns of lesions. Twelve cases had localised periosteal/cortical lesions of
      the ventral aspect of the angle of mandible that were most likely traumatic in
      origin. The remaining seven undiagnosed cases without mandibular bony changes all
      had sinus tracts/chronic soft tissue infections on the medial aspect of the angle
      of the mandible which were believed to be caused by a draining retro-pharyngeal
      lesion in five cases. Surgical excision of abnormal soft tissues (if present) and
      bone curettage was the most successful treatment. It was concluded that the
      aetiology of swellings of the angle of the equine mandible are often obscure;
      most appear to be traumatic in origin, yet horses seldom develop gross fractures
      at this site due to the support of the dense surrounding musculo-tendinous
      structures. A smaller proportion are caused by draining retropharyngeal lesions
      that respond poorly to medical therapy, but respond well to surgical treatment. 

PMID- 24290989
TI  - A twist in the heart.

PMID- 24290990
TI  - Should evolutionary geneticists worry about higher-order epistasis?
AB  - Natural selection drives evolving populations up the fitness landscape, the
      projection from nucleotide sequence space to organismal reproductive success.
      While it has long been appreciated that topographic complexities on fitness
      landscapes can arise only as a consequence of epistatic interactions between
      mutations, evolutionary genetics has mainly focused on epistasis between pairs of
      mutations. Here we propose a generalization to the classical population genetic
      treatment of pairwise epistasis that yields expressions for epistasis among
      arbitrary subsets of mutations of all orders (pairwise, three-way, etc.). Our
      approach reveals substantial higher-order epistasis in almost every published
      fitness landscape. Furthermore we demonstrate that higher-order epistasis is
      critically important in two systems we know best. We conclude that higher-order
      epistasis deserves empirical and theoretical attention from evolutionary
      geneticists. 

PMID- 24290992
TI  - Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment
      planning systems: a dosimetric study.
AB  - PURPOSE: Late toxicities such as second cancer induction become more important as
      treatment outcome improves. Often the dose distribution calculated with a
      commercial treatment planning system (TPS) is used to estimate radiation
      carcinogenesis for the radiotherapy patient. However, for locations beyond the
      treatment field borders, the accuracy is not well known. The aim of this study
      was to perform detailed out-of-field-measurements for a typical radiotherapy
      treatment plan administered with a Cyberknife and a Tomotherapy machine and to
      compare the measurements to the predictions of the TPS. MATERIALS AND METHODS:
      Individually calibrated thermoluminescent dosimeters were used to measure
      absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose
      distributions from 6 MV intensity-modulated treatment beams for CyberKnife and
      TomoTherapy machines were compared to the dose calculations from the TPS.
      RESULTS: The TPS are underestimating the dose far away from the target volume.
      Quantitatively the Cyberknife underestimates the dose at 40 cm from the PTV
      border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose
      uncertainty is accepted, the Cyberknife TPS can predict doses down to
      approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment
      Gy. The Cyberknife TPS can then be used up to 10 cm from the PTV border the
      Tomotherapy up to 35 cm. CONCLUSIONS: We determined that the Cyberknife and
      Tomotherapy TPS underestimate substantially the doses far away from the treated
      volume. It is recommended not to use out-of-field doses from the Cyberknife TPS
      for applications like modeling of second cancer induction. The Tomotherapy TPS
      can be used up to 35 cm from the PTV border (for a 390 cm(3) large PTV).

PMID- 24290991
TI  - Expression of integrins alpha3beta1 and alpha5beta1 and GlcNAc beta1,6 glycan
      branching influences metastatic melanoma cell migration on fibronectin.
AB  - Acquisition of metastatic potential is accompanied by changes in cell surface N
      glycosylation. One of the best-studied changes is increased expression of N
      acetylglucosaminyltransferase V enzyme (GnT-V) and its products, beta1,6-branched
      N-linked oligosaccharides, observed in the tumorigenesis of many cancers. In this
      study we demonstrate that during the transition from the vertical growth phase
      (VGP) (WM793 cell line) to the metastatic stage (WM1205Lu line), beta1,6
      glycosylation of melanoma cell surface proteins increases as a consequence of
      elevated expression of the GnT-V-encoding Mgat-5 gene. Treatment with swainsonine
      led to reduced cell motility on fibronectin in both cell lines; the effect was
      stronger in metastatic cells, probably due to the higher content of GlcNAc
      beta1,6-branched glycans on the main fibronectin receptors - integrins
      alpha5beta1 and alpha3beta1. Our results show that GlcNAc beta1,6 N-glycosylation
      of cell surface receptors, which increases with the aggressiveness of melanoma
      cells, is an important factor influencing melanoma cell migration. 

PMID- 24290993
TI  - Chemical peels: panel discussion.
AB  - Edwin Cortez, Fred Fedok, and Devinder Mangat address questions for discussion
      and debate. Do you agree or disagree, and why, with the following: "The best
      method to improve moderate to deep rhytids is the croton oil-phenol peel." "There
      are no problems with cardiotoxicity with croton oil-phenol peels if done
      appropriately." "Do not do spot testing with chemical peel agents." How do you
      handle peels in advanced Fitzpatrick skin types III, IV, V? What is the main
      factor for rate of reepithelialization: (1) depth of peel, (2) depth of laser,
      (3) depth of dermabrasion? How has your approach to or technique in chemical
      peels evolved over the past several years? 

PMID- 24290994
TI  - Rhinoplasty: panel discussion.
AB  - Should one use an open or closed rhinoplasty approach? How appropriate is the
      endonasal approach in modern-day rhinoplasty? Should the tip lobule be divided or
      preserved? Are alloplastic implants inferior to autologous implants? Does release
      and reduction of the upper lateral cartilages from the nasal dorsal septum always
      require spreader graft placement to prevent mid one-third nasal pinching in
      reduction rhinoplasty? Over past 5 years, how have rhinoplasty techniques and
      approaches evolved? 

PMID- 24290995
TI  - Revision rhinoplasty: panel discussion, controversies, and techniques.
AB  - What is the single most difficult challenge in revision rhinoplasty and how do
      you address it? During revision rhinoplasty, when dorsal augmentation is
      necessary and septal and ear cartilage is not available, what is the best
      substance for correcting the problem? If rib cartilage is used for dorsal
      augmentation during revision rhinoplasty, what is the technique to prevent
      warping of the graft? Alloplast in the nose--when, where, and for what purpose?
      Does the release and reduction of the upper lateral cartilages from the nasal
      dorsal septum always require spreader graft placement to prevent mid-one-third
      nasal pinching in reductive rhinoplasty?' ANALYSIS: Over the past 5 years, how
      has your technique evolved or what have you observed and learned in performing
      revision rhinoplasty?

PMID- 24290996
TI  - Lower lid blepharoplasty: panel discussion, controversies, and techniques.
AB  - What is the most frequent displeasing effect you see when performing lower eyelid
      blepharoplasty? What surgical approach do you most frequently use when performing
      lower eyelid blepharoplasty? How much skin removal of the lower eyelids? When
      performing lower lid blepharoplasty, what is your preferred method of managing
      pseudoherniated fat? If you perform midface lifting during blepharoplasty, what
      approach do you use? ANALYSIS: Over the past 5 years, how has your technique or
      approach evolved or what is the most important thing you have learned in doing
      blepharoplasty?

PMID- 24290997
TI  - Midface lift: panel discussion.
AB  - What is the most efficient dissection plane to perform midface lift? What is the
      best incision/approach (preauricular, transtemporal, transoral)? Why? What
      specific technique do you use? Why? What is the best method/substance for adding
      volume to midface lifting? In approaching the midface, how do you see the
      relationship of blepharoplasty versus fillers versus midface lifting? ANALYSIS:
      How has your procedure or approach evolved over the past 5 years? What have you
      learned, first-person experience, in doing this procedure?

PMID- 24290999
TI  - Discussion and debate among facial plastic surgeons: everyone wins.

PMID- 24290998
TI  - Distraction osteogenesis.
AB  - James Sidman, MD, and Sherard A. Tatum, MD, address the following questions for
      discussion and debate. Is neonatal distraction osteogenesis (DO) better than lip
      tongue adhesion or tracheotomy for micrognathic airway compromise? What role does
      DO have in adult orthognathic surgery situations? In monobloc and Le Fort III
      procedures, are internal or external devices preferable? What role does DO play
      in craniofacial microsomia? Is endoscopic DO better than open procedures for
      synostosis management? How has your technique changed or evolved over the past 5
      years and what has doing this technique taught you?

PMID- 24291000
TI  - Ionizing radiation doses during lower limb torsion and anteversion measurements
      by EOS stereoradiography and computed tomography.
AB  - OBJECTIVES: To calculate and compare the doses of ionizing radiation delivered to
      the organs by computed tomography (CT) and stereoradiography (SR) during
      measurements of lower limb torsion and anteversion. MATERIALS AND METHODS: A
      Rando anthropomorphic phantom (Alderson RANDO phantom, Alderson Research
      Laboratories Inc., Stanford, Conn) was used for the dose measurements. The doses
      were delivered by a Somatom 16-slice CT-scanner (Siemens, Erlangen) and an EOS
      stereoradiography unit (EOS-Imaging, Paris) according to the manufacturers'
      acquisition protocols. Doses to the surface and deeper layers were calculated
      with thermoluminiscent GR207P dosimeters. Dose uncertainties were evaluated and
      assessed at 6% at k=2 (that is, two standard deviations). RESULTS: The absorbed
      doses for the principal organs assessed were as follows: for the ovaries, 0.1 mGy
      to the right ovary and 0.5 mGy to the left ovary with SR versus 1.3 mGy and 1.1
      mGy with CT, respectively; testes, 0.3 mGy on the right and 0.4 mGy on the left
      with SR versus 8.5 mGy and 8.4 mGy with CT; knees, 0.4 mGy to the right knee and
      0.8 mGy to the left knee with SR versus 11 mGy and 10.4 mGy with CT; ankles, 0.5
      mGy to the right ankle and 0.8 mGy to the left with SR versus 15 mGy with CT.
      CONCLUSION: The SR system delivered substantially lower doses of ionizing
      radiation doses than CT to all the organs studied: CT doses were 4.1 times higher
      to the ovaries, 24 times higher for the testicles, and 13-30 times higher for the
      knees and ankles. The use of the SR system to study the torsion of lower limbs
      makes it possible to reduce the amount of medical irradiation that patients
      accumulate.

PMID- 24291001
TI  - Degradable starch microspheres versus ethiodol and doxorubicin in transarterial
      chemoembolization of hepatocellular carcinoma.
AB  - PURPOSE: To compare outcomes of transarterial chemoembolization with degradable
      starch microspheres (DSMs) and conventional transarterial chemoembolization with
      doxorubicin and Ethiodol in patients with unresectable intermediate-stage
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 69 patients
      underwent 169 chemoembolization procedures with Ethiodol (n = 35) or DSMs (n =
      34) as the embolic agent. The same chemotherapeutic agent was used for all
      patients (50 mg doxorubicin). The primary endpoint was patient survival, and
      secondary endpoints were local tumor response and incidence of therapy-associated
      complications with conventional or DSM chemoembolization. Tumor response was
      evaluated by consensus reading by two radiologists in accordance with modified
      Response Evaluation Criteria In Solid Tumors. Mean survival was calculated
      according to Kaplan-Meier analysis, and differences in survival curves were
      assessed by univariate log-rank test. The statistical significance of
      quantitative variables was determined by parameter-free Wilcoxon-Mann-Whitney U
      test. RESULTS: The study groups were similar with regard to demographic data and
      disease stage. For the DSM chemoembolization group, the objective response rate
      (ie, complete or partial response) was 44.1%, and the rate of stable disease was
      38.2%. The respective rates for the conventional chemoembolization group were
      48.6% and 31.4%. Mean survival (P = .337) and complications did not significantly
      differ between groups (P = .907; P = 1.000). CONCLUSIONS: DSM chemoembolization
      represents an alternative method of HCC treatment with a safety profile similar
      to that of conventional transarterial chemoembolization. Regarding local tumor
      response and overall survival, results of DSM chemoembolization were similar to
      those of conventional chemoembolization.

PMID- 24291002
TI  - Sonoporation-mediated transduction of siRNA ameliorated experimental arthritis
      using 3 MHz pulsed ultrasound.
AB  - The goal of this feasibility study was to examine whether sonoporation assisted
      transduction of siRNA could be used to ameliorate arthritis locally. If
      successful, such approach could provide an alternative treatment for the patients
      that have or gradually develop adverse response to chemical drugs. Tumor necrosis
      factor alpha (TNF-alpha) produced by synovial fibroblasts has an important role
      in the pathology of rheumatoid arthritis, inducing inflammation and bone
      destruction. In this study, we injected a mixture of microbubbles and siRNA
      targeting TNF-alpha (siTNF) into the articular joints of rats, and transduced
      siTNF into synovial tissue by exposure to a collimated ultrasound beam, applied
      through a probe 6mm in diameter with an input frequency of 3.0 MHz, an output
      intensity of 2.0 W/cm(2) (spatial average temporary peak; SATP), a pulse duty
      ratio of 50%, and a duration of 1 min. Sonoporation increased skin temperature
      from 26.8  degrees C to 27.3  degrees C, but there were no adverse effect such as
      burns. The mean level of TNF-alpha expression in siTNF-treated knee joints was
      55% of those in controls. Delivery of siTNF into the knee joints every 3 days
      (i.e., 7, 10, 13, and 16 days after immunization) by in vivo sonoporation
      significantly reduced paw swelling on days 20-23 after immunization. Radiographic
      scores in the siTNF group were 56% of those in the CIA group and 61% of those in
      the siNeg group. Histological examination showed that the number of TNF-alpha
      positive cells was significantly lower in areas of pannus invasion into the ankle
      joints of siTNF- than of siNeg-treated rats. These results indicate that
      transduction of siTNF into articular synovium using sonoporation may be an
      effective local therapy for arthritis.

PMID- 24291003
TI  - One step backwards, two steps ahead: amplifying movement errors to improve
      walking post-stroke.

PMID- 24291005
TI  - Comparative study on short- and long-term behavioral consequences of
      organophosphate exposure: relationship to AChE mRNA expression.
AB  - Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE).
      While the cognitive short-term effects may be directly attributed to this
      inhibition, the mechanisms that underlie OP's long-term cognitive effects remain
      controversial and poorly understood. Accordingly, two experiments were designed
      to assess the effects of OPs on cognition, and to ascertain whether both the
      short- and long-term effects of are AChE-dependent. A single subcutaneous dose of
      250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15
      mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was
      evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10
      and 30 weeks following OPs administration (experiment 1 and 2, respectively).
      Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read
      through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as
      alternative non-cholinergic target) were analyzed upon completion of the
      behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long
      term CPF treatment caused statistically significant effects on spatial learning,
      while PTN treatment led only to statistically significant short-term effects.
      Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term
      exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in
      the PTN treated group only AChE-S mRNA levels were decreased. However, after long
      term OP exposure, soluble and membrane-bound AChE activity was indistinguishable
      from controls. Finally, no changes were noted in brain APH activity in response
      to OP treatment. Taken together, this study demonstrates long-term effects of OPs
      on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane
      bound activity. Thus, changes in AChE mRNA expression imply non-catalytic
      properties of the AChE enzyme.

PMID- 24291006
TI  - Combined transbronchial needle aspiration and (99m)Tc-2-methoxy-isobutyl
      isonitrile single photon emission computed tomography for diagnosing enlarged
      mediastinal lymph nodes.
AB  - BACKGROUND: To demonstrate the diagnostic accuracy of an integrated approach of
      blind trans-bronchial needle aspiration (TBNA) and (99m)Tc-2-methoxy-isobutyl
      isonitrile single photon emission computed tomography ((99m)Tc-MIBI-SPECT) in
      diagnosing mediastinal lymph adenopathy. METHODS: Sixty one consecutive patients
      with mediastinal lymph adenopathy undergoing both TBNA and (99m)Tc-MIBI-SPECT
      were prospectively enrolled. Mediastinoscopy was attended in case of negative
      TBNA. RESULTS: Eighty three adenopathies were sampled (73 malignant and 10
      benign). Sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV) of TBNA was 74%, 100%, 100%, and 34%, respectively; and of
      (99m)Tc-MIBI-SPECT was 96%, 80%, 97%, and 73%, respectively. Combining TBNA and
      (99m)Tc-MIBI-SPECT results sensitivity, specificity, PPV, NPV of 97%, 100%, 100%,
      and 83%, respectively, was obtained. TBNA alone avoided medistianoscopy in 65% of
      cases, while an integrated approach could have potentially obviated
      mediastinoscopy in 76%. CONCLUSIONS: (99m)Tc-MIBI-SPECT improved the sensitivity
      and the NPV of TBNA, reducing the need of mediastinoscopy.

PMID- 24291007
TI  - Trehalose 6-phosphate phosphatase is required for development, virulence and
      mycotoxin biosynthesis apart from trehalose biosynthesis in Fusarium graminearum.
AB  - Trehalose 6-phosphate synthase (TPS1) and trehalose 6-phosphate phosphatase
      (TPS2) are required for trehalose biosynthesis in yeast and filamentous fungi,
      including Fusarium graminearum. Three null mutants Deltatps1, Deltatps2 and
      Deltatps1-Deltatps2, each carrying either a single deletion of TPS1 or TPS2 or a
      double deletion of TPS1-TPS2, were generated from a toxigenic F. graminearum
      strain and were not able to synthesize trehalose. In contrast to its reported
      function in yeasts and filamentous fungi, TPS1 appeared dispensable for
      development and virulence. However, deletion of TPS2 abolished sporulation and
      sexual reproduction; it also altered cell polarity and ultrastructure of the cell
      wall in association with reduced chitin biosynthesis. The cell polarity
      alteration was exhibited as reduced apical growth and increased lateral growth
      and branching with increased hyphal and cell wall widths. Moreover, the TPS2
      deficient strain displayed abnormal septum development and nucleus distribution
      in its conidia and vegetative hyphae. The Deltatps2 mutant also had 62% lower
      mycelial growth on potato dextrose agar and 99% lower virulence on wheat compared
      with the wild-type. The Deltatps1, Deltatps2 and Deltatps1-Deltatps2 mutants
      synthesized over 3.08-, 7.09- and 2.47-fold less mycotoxins, respectively, on
      rice culture compared with the wild-type. Comparative transcriptome analysis
      revealed that the Deltatps1, Deltatps2 and Deltatps1-Deltatps2 mutants had 486,
      1885 and 146 genotype-specific genes, respectively, with significantly changed
      expression profiles compared with the wild-type. Further dissection of this
      pathway will provide new insights into regulation of fungal development,
      virulence and trichothecene biosynthesis. 

PMID- 24291004
TI  - Direct reversal of glucocorticoid resistance by AKT inhibition in acute
      lymphoblastic leukemia.
AB  - Glucocorticoid resistance is a major driver of therapeutic failure in T cell
      acute lymphoblastic leukemia (T-ALL). Here, we identify the AKT1 kinase as a
      major negative regulator of the NR3C1 glucocorticoid receptor protein activity
      driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 impairs
      glucocorticoid-induced gene expression by direct phosphorylation of NR3C1 at
      position S134 and blocking glucocorticoid-induced NR3C1 translocation to the
      nucleus. Moreover, we demonstrate that loss of PTEN and consequent AKT1
      activation can effectively block glucocorticoid-induced apoptosis and induce
      resistance to glucocorticoid therapy. Conversely, pharmacologic inhibition of AKT
      with MK2206 effectively restores glucocorticoid-induced NR3C1 translocation to
      the nucleus, increases the response of T-ALL cells to glucocorticoid therapy, and
      effectively reverses glucocorticoid resistance in vitro and in vivo.

PMID- 24291008
TI  - Exploring the protective role of apocynin, a specific NADPH oxidase inhibitor, in
      cisplatin-induced cardiotoxicity in rats.
AB  - Despite the clinical reports, few studies have focused on reducing the
      cardiotoxicity of cisplatin. In the present study, cardiotoxicity was examined
      after a single ip injection of cisplatin (7mg/kg) in rats. Apocynin was given in
      drinking water (600mg/L) for five successive days before and after cisplatin
      injection. At the end of the experiment, hemodynamic parameters were recorded,
      animals were sacrificed and serum creatine kinase-MB activity was determined. The
      whole ventricle was isolated for estimation of tumor necrosis factor-alpha (TNF
      alpha) content, NADPH oxidase, myeloperoxidase and caspase-3 activities in
      addition to nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1
      (HO-1) and nuclear factor kappa B (NF-kappaB) gene expressions. Furthermore,
      oxidative stress markers and antioxidant enzymes were measured in
      postmitochondrial and mitochondrial fractions. Mitochondrial membrane potential,
      nuclear DNA fragmentation and cardiomyocyte cross-sectional area were also
      evaluated. Apocynin was effective against cisplatin-induced decrement in heart
      rate and blood pressure. Moreover, pretreatment with apocynin notably ameliorated
      the state of oxidative stress, mitigated inflammation and preserved mitochondrial
      membrane potential. Apocynin provided also a significant cardioprotection as
      revealed by alleviating the overexpression of Nrf2, HO-1 and NF-kappaB, the
      elevation of caspase-3 activity, the prominent nuclear DNA fragmentation and the
      decreased cardiomyocyte cross-sectional area. This study highlights the potential
      role of apocynin in inhibiting cisplatin-induced hemodynamic changes,
      postmitochondrial and mitochondrial damage as indicated by improvement in the
      state of oxidative stress, inflammation and apoptosis. 

PMID- 24291009
TI  - Morphological and physicochemical characterization of liposomes loading
      cucurbitacin E, an anti-proliferative natural tetracyclic triterpene.
AB  - Cucurbitacin E (Cuc E), an oxygenated triterpene molecule, has demonstrated anti
      proliferative effect on various cancer cells. Here, we examined the effect of Cuc
      E on the membrane morphology and properties using differential scanning
      calorimetry, transmission electron microscopy and atomic force microscopy
      techniques. Dipalmitoylphosphatidylcholine vesicles were prepared by the thin
      film hydration method in the absence and presence of Cuc E at molar ratios 100:12
      and 100:20. The loading efficiency of Cuc E was found to be higher than 98% upon
      HPLC analysis. The thermodynamic parameters suggest that Cuc E does not penetrate
      into the bilayers and interacts with the polar/apolar interface of the lipid
      membranes. Blank and Cuc E loaded liposomes prepared from a mixture of
      DPPC/DPPE/DPPG/Cho were imaged by TEM and AFM. Images obtained by TEM revealed
      unilamellar liposomes for blank and Cuc E loaded liposomes. AFM images showed
      that the size and the height of Cuc E loaded liposomes were respectively smaller
      and higher than blank ones. Results suggest that Cuc E produces modifications in
      the lipid membrane structures. 

PMID- 24291010
TI  - The Y-organ secretory activity fluctuates in relation to seasons of molt and
      reproduction in the brachyuran crab, Metopograpsus messor (Grapsidae):
      Ultrastructural and immunohistochemical study.
AB  - This paper presents a first-time report on the localization, structure and
      seasonal secretory activity of the Y-organ of a grapsid brachyuran crab
      (Metopograpsus messor). Having exhibited discrete seasonality with reference to
      the programming of molt and reproduction, this brachyuran crab has offered us an
      excellent model to obtain a clear picture of the fluctuating secretory nature of
      the Yorgan, all the way through the reproductive (August-December) as well as the
      molt-reproduction active (January-May) and inactive (June-July) seasons.
      Ultrastructural studies revealed that the secretion of the Y-organ was at its
      peak in premolt crabs during molt-reproduction season (January-May).
      Interestingly, the Y-organs of the intermolt females that engaged in breeding
      activity showed higher levels of secretion than those of the molt-reproduction
      inactive season (June-July), implicating the gland's involvement in reproduction.
      Immunohistochemical studies using the antiserum raised against 2-succinyl
      conjugate of ecdysone have demonstrated the ecdysteroid nature of the secretion
      from the Y-organ, and results of the quantitative assay of ecdysteroids (through
      radioimmunoassay) revealed that the hormone titer fluctuates in consonance with
      the Y-organ's secretory activity during seasons of molt and reproduction.
      Pertinently, not only that the paper gives us a comprehensive understanding on
      the secretory activity of the Y-organ in a season-dependent fashion, it also
      allows us to have a better insight into the gland's function related to molting
      and reproduction (for the first time) in a grapsid brachyuran crab. 

PMID- 24291011
TI  - Phylogenetic analysis of the polyprotein coding region of an infectious South
      African bursal disease virus (IBDV) strain.
AB  - Infectious bursal disease virus (IBDV) causes Gumboro disease, which is highly
      contagious and immunosuppressive in young chickens. A virulent form of IBDV
      reached South Africa in 1989 and to date there has been little molecular
      information available for this strain. In this study, the polyprotein coding
      region of the South African strain SA-KZN95 was sequenced and analysed along with
      52 representative sequences of other serotype I and II strains. We explored the
      relative impact of recombination on phylogenetic reconstruction using a
      multidimensional scaling approach. Phylogenetic analyses consistently placed the
      South African isolate within the very virulent IBDV clade. Selection analyses
      were also conducted to identify evolutionarily relevant amino acid residues.
      Previously, 19 residues in the polyprotein were shown to be potentially
      diagnostic for the different IBDV pathotypes. This study identified an additional
      two unique residues in the polyprotein which may be used as genetic signatures in
      future viral identifications. Better strain identification would aid in the
      development and application of vaccines. 

PMID- 24291012
TI  - Genome-wide scan for analysis of simple and imperfect microsatellites in diverse
      carlaviruses.
AB  - An exhaustive compilation and analysis of incidence, distribution and variation
      of simple sequence repeats (SSRs) in viruses are required to understand the
      evolution and functional aspects of repetitive sequences. Present study focuses
      on the analysis of SSRs in 32 species of carlaviruses. The full length genome
      sequences were assessed from NCBI (http://www.ncbi.nlm.nih.-gov/) and analyzed
      using IMEx software. Variance in incidence of SSRs was observed, independent of
      genome size. Though the conversion of SSRs to imperfect microsatellite or
      compound SSR is low; compound microsatellites constituted by variant motifs
      accounted for up to 12.5% of the SSRs. Mononucleotide A/T is most prevalent
      followed by dinucleotide GT/TG and trinucleotide AAG/GAA in these genomes. The
      SSR and cSSR are predominantly localized to the coding region RDRP (RNA dependent
      RNA polymerase) and ORF-6 (open reading frame). The relative frequency of
      different classes of simple and compound microsatellites has been highlighted in
      accordance with the biology of carlavirus. Characterization of such variations
      would be pivotal for deciphering the enigma of these widely used, but
      incompletely understood sequences. 

PMID- 24291013
TI  - Significant underuse of warfarin in patients with nonvalvular atrial
      fibrillation: results from the China national stroke registry.
AB  - BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial
      fibrillation (AF) but is often underused in clinical practice. We aimed to
      examine the current state of warfarin use in nonvalvular atrial fibrillation
      (NVAF) patients with first-ever ischemic stroke (IS) or transient ischemic attack
      (TIA) in China and to analysis factors causing such underuse. METHODS: By
      accessing the China National Stroke Registry, data on consecutive patients with
      known NVAF who developed first-ever IS or TIA were studied. Proportion of
      warfarin use was estimated in those patients with known NVAF who should be
      eligible for anticoagulation therapy. Factors associated with warfarin underuse
      were identified by multivariate logistic regression. RESULTS: Of 11,080 patients
      with first-ever IS or TIA, 996 (9.7%) had NVAF and no contraindications to
      anticoagulation therapy and 592 of them had history of AF. Among these patients,
      only 96 (16.2%) were on warfarin and 496 (83.8%) were not. In those patients on
      warfarin, only 1 of his international normalized ratios on admission was in the
      therapeutic range of 2.0-3.0. Based on the CHADS2 scores, about 20.2% low-risk AF
      patients took warfarin; however, only 15.2% moderate and 16.4% high-risk patients
      were on warfarin. Older patients and patients with history of coronary heart
      disease (CHD) were less likely to be given warfarin, whereas patients with
      history of prestroke antiplatelet use were more likely to take warfarin.
      CONCLUSIONS: We found that warfarin was significantly underused in patients with
      known NVAF in China. Age and CHD and prestroke antiplatelet therapy were related
      factors.

PMID- 24291014
TI  - Effect of tissue plasminogen activator dose and interval on stroke severity.

PMID- 24291015
TI  - Response to "Effect of tissue plasminogen activator dose and interval on stroke
      severity".

PMID- 24291016
TI  - Antimicrobial and antioxidative activity of extracts and essential oils of Myrtus
      communis L.
AB  - Since synthetic antimicrobial agents and food additives can cause a number of
      adverse effects, there is a growing interest from consumers in ingredients from
      natural sources. Medicinal plants, such as Myrtus communis L. are a source of new
      compounds which can be used in both the food industry and for medical purposes,
      primarily as antimicrobial agents. In this review, the characteristics of myrtle
      essential oils and extracts are summarized, with particular attention to their
      chemical composition, biological activities and potential applications. 

PMID- 24291018
TI  - Increased responsiveness to thrombin through protease-activated receptors (PAR)-1
      and -4 in active Crohn's disease.
AB  - BACKGROUND AND AIMS: Platelets are essential in hemostasis and inflammation,
      thereby linking coagulation with inflammation. Abundant thrombin generation in
      association with inflammation is considered a major reason for the increased risk
      for thromboembolic events. We therefore investigated platelet responsiveness to
      thrombin. METHODS: In this case-control study 85 patients with Crohn's disease
      (active CD 42, remission 43) and 30 sex- and age-matched controls were enrolled.
      Clinical disease activity (Harvey-Bradshaw-Index) was assessed and CD-related
      data were determined by chart review. Platelets' response to protease activated
      receptor-1 and -4 (PAR-1, -4) was assessed by whole blood platelet aggregometry
      (MEA), levels of platelets adhering to monocytes (PMA), and platelet surface P
      selectin. RESULTS: Platelets' aggregation after activation with the specific PAR
      1 agonist (SFLLRN) and PAR-4 agonist (AYPGKF) was higher in patients with active
      CD compared to patients in remission and controls (p=0.0068 and p=0.0023 for
      SFLLRN, p=0.0019 and 0.0003 for AYPGKF). Likewise, levels of PMA after activation
      with PAR-1 and PAR-4 receptor agonists were higher in patients with active CD
      compared to patients in remission and controls (p=0.0001 and p<0.0001 for SFLLRN,
      p=0.0329 and p=0.0125 for AYPGKF). However, P-selectin expression on human
      platelets showed heterogeneous results. Only PAR-1 activation of platelets
      resulted in significant differences between CD patients and controls (p=0.0001
      and p=0.0022 for active and inactive CD versus controls, respectively).
      CONCLUSIONS: Our data suggest a new mechanism of platelet activation which has
      the potential to increase risk for thromboembolism in patients with active CD
      which might be due to platelets poised for thrombin-inducible activation.

PMID- 24291019
TI  - Infliximab induced liver injury in Crohn's disease: a challenging diagnosis.

PMID- 24291017
TI  - Phenotypic and functional heterogeneity of CD169+ and CD163+ macrophages from
      porcine lymph nodes and spleen.
AB  - Secondary lymphoid organ macrophages are involved in the establishment of innate
      and acquired immunity. Here, we have isolated and characterized porcine lymph
      node and spleen CD169(+) and spleen CD163(+) macrophages. Lymph node and spleen
      CD169(+) macrophages can be both identified as CD172a(+)SLA
      DR(hi)CD80/86(hi)CD14(int)TLR2(+)TLR4(+). On the other side, spleen CD163(+)
      macrophages are CD172a(+)SLA-DR(int)CD80/86(int)CD14(-)/(lo)TLR2(int)TLR4(int).
      In addition, these macrophages can be subdivided based on the expression of
      CD11R1 or CD11R3. Lymph node CD169(+) macrophages phagocytozed polystyrene
      microspheres more efficiently than spleen CD163(+) and CD169(+) macrophages. All
      macrophages exhibited low capacity to take up and process the soluble antigen DQ
      OVA. Finally, spleen CD163(+) macrophages displayed the highest ability to
      present lysozyme to CD4(+) T cells in a secondary in vitro response, followed by
      lymph node and spleen CD169(+) macrophages. 

PMID- 24291020
TI  - Kaposi's sarcoma developing in a HIV-negative Crohn's disease patient shortly
      after azathioprine and corticosteroid treatment.

PMID- 24291022
TI  - The lectin pathway of the complement system is downregulated in Crohn's disease
      patients who respond to anti-TNF-alpha therapy.
AB  - BACKGROUND AND AIMS: The lectin pathway of the complement system is initiated
      through the recognition of pathogens or altered self-structures by mannan-binding
      lectin (MBL) or ficolins and subsequent activation of MBL-associated serine
      proteases (MASPs). Altered ficolin levels may contribute to a dysregulated immune
      response in Crohn's disease (CD). A complete analysis of the lectin pathway has
      not been performed in patients with CD. We hypothesised that the lectin pathway
      proteins exacerbate inflammation in CD. METHODS: We assessed the lectin pathway
      proteins in 43 patients with active CD & 350 blood donors by measuring the serum
      levels of MBL; M-, H-, and L-ficolin; MASP-2; MASP-3; and MAp44. In patients with
      CD, the blood samples were obtained during induction treatment with infliximab or
      adalimumab. RESULTS: Of 43 patients with CD, 32 (74%) were classified as
      responders. We observed a nearly 50% decrease in median M-ficolin levels between
      day 0 and weeks 1/7 in the responders (p<0.001), whereas there was no decrease in
      the non-responders. MASP-2 levels decreased from baseline to week 1 in both the
      responders (37%, p<0.0001) and the non-responders (29%, p=0.02). In the
      responders only, the level of the inhibitory serine protease MASP-3 increased by
      26% from baseline to week 1 (p<0.001) and remained high at week 7. CONCLUSIONS:
      Our findings indicated that M-ficolin, MASP-2, and MASP-3 may act in concert to
      reduce the activity of the lectin pathway, in patients with CD who respond to
      biological therapy.

PMID- 24291021
TI  - Total soluble and endogenous secretory receptor for advanced glycation
      endproducts (RAGE) in IBD.
AB  - BACKGROUND AND AIMS: Recruitment and activation of neutrophils, with release of
      specific proteins such as S100 proteins, is a feature of inflammatory bowel
      disease (IBD). Soluble forms of the receptor for advanced glycation endproducts
      (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy
      receptors by binding ligands, including S100A12. The aims of this study were to
      determine total sRAGE and esRAGE concentrations in patients with IBD and
      correlate these with C-reactive protein (CRP), endoscopic scores and clinical
      disease activity scores. METHODS: EDTA-plasma was collected from patients
      undergoing colonoscopy including those with Crohn's disease (CD: n=125),
      ulcerative colitis (UC: n=79) and control patients without endoscopic signs of
      inflammation (non-IBD: n=156). Concentrations of sRAGE and esRAGE were determined
      by enzyme-linked immunosorbent assay and plasma CRP concentrations measured.
      Standard clinical disease activity and endoscopic severity scores were defined
      for all subjects. RESULTS: Plasma sRAGE concentrations were lower in UC (but not
      CD) than non-IBD subjects (p<0.01). Whilst sRAGE concentrations correlated
      negatively with endoscopic activity in UC (p<0.05), this was not seen in CD. In
      contrast, esRAGE correlated negatively with disease activity in both UC (p=0.002)
      and CD (p=0.0001). Furthermore, sRAGE and esRAGE concentrations correlated
      inversely with CRP values (p<0.0001). CONCLUSIONS: Although total sRAGE varied
      with activity in UC, esRAGE concentrations correlated inversely with endoscopic
      disease activity and CRP levels in both UC and CD. Additional studies are
      required to further define the significance of sRAGE and esRAGE in IBD.

PMID- 24291023
TI  - Functional movement screen test: a reliable screening test for young elite ice
      hockey players.
AB  - OBJECTIVES: To determine inter-rater and intra-rater reliability of the
      Functional Movement Screen (FMS) test among young elite hockey players. DESIGN:
      Reliability study. SETTING: Inter-rater reliability was evaluated by two raters
      in the field. All performances were videotaped. Two other raters evaluated the
      videos once and then again 6 weeks later to determine intra-rater reliability. A
      weighted kappa statistic was used to analyze intra-rater and inter-rater
      reliability of each FMS sub-test, while an intra-class correlation coefficient
      (ICC) was calculated for the total score. PARTICIPANTS: Twenty-eight male hockey
      players aged 13-16. MAIN OUTCOME: FMS total and sub-tests scores. RESULTS: The
      video raters demonstrated excellent intra-rater reliability for the total score,
      with an ICC of 0.96 (95% CI; 0.92-0.98) and 0.96 (95% CI; 0.91-0.98). The field
      raters achieved excellent inter-rater reliability for the total score, with an
      ICC of 0.96 (95% CI; 0.92-0.98). Sub-test analysis showed good agreement among
      all four raters for five of the seven main sub-tests. CONCLUSION: FMS is a
      reliable test for young elite hockey players. Further research should be done to
      assess the predictive validity of the FMS test within this population so that
      physiotherapists may eventually use it as an injury prevention tool.

PMID- 24291024
TI  - Working memory modulates neural efficiency over motor components during a novel
      action planning task: an EEG study.
AB  - Research shows neural efficiency of motor-related activity based on learning and
      expertise in a specific domain (e.g., guitar playing, sharp-shooting or a sport).
      However, it is unknown whether neural efficiency of motor-related activity,
      underlying action planning and maintenance, can be modulated by general cognitive
      ability alone. This study examined whether working memory span can influence
      motor-related neural activity during a novel motor task. Participants were
      divided into low- and high-span working memory groups based on their scores in an
      operation span task. Afterwards, participants learned different sequences of
      button responses corresponding to different abstract stimuli. The task required
      participants to briefly maintain an action plan in working memory to a stimulus
      that they would execute after responding to a subsequent stimulus. We used EEG to
      record changes in event related power in the mu- and beta-bands in left and right
      motor components during the interval where participants planned and maintained an
      action in working memory. Results showed decreases in mu- and beta-event related
      power for low-span participants and increases in mu- and beta-event related power
      for high-span participants over the left motor cluster while maintaining an
      action plan in working memory. Also, high-span participants were faster and more
      accurate in the task than low-span participants. This suggests that neural
      efficiency during a novel motor task can be influenced by working memory span,
      and that such differences are localized to the motor system. 

PMID- 24291025
TI  - Understanding the transcriptional regulation of cervix cancer using microarray
      gene expression data and promoter sequence analysis of a curated gene set.
AB  - Cervical cancer, the malignant neoplasm of the cervix uteri is the second most
      common cancer among women worldwide and the top-most cancer in India. Several
      factors are responsible for causing cervical cancer, which alter the expression
      of oncogenic genes resulting in up or down-regulation of gene expression and
      inactivation of tumor-suppressor genes/gene products. Gene expression is
      regulated by interactions between transcription factors (TFs) and specific
      regulatory elements in the promoter regions of target genes. Thus, it is
      important to decipher and analyze TFs that bind to regulatory regions of diseased
      genes and regulate their expression. In the present study, computational methods
      involving the combination of gene expression data from microarray experiments and
      promoter sequence analysis of a curated gene set involved in the cervical cancer
      causation have been utilized for identifying potential regulatory elements.
      Consensus predictions of two approaches led to the identification of twelve TFs
      that might be crucial to the regulation of cervical cancer progression.
      Subsequently, TF enrichment and oncomine expression analysis suggested that the
      transcription factor family E2F played an important role for the regulation of
      genes involve in cervical carcinogenesis. Our results suggest that E2F possesses
      diagnostic/prognostic value and can act as a potential drug target in cervical
      cancer. 

PMID- 24291026
TI  - Array CGH analysis of a cohort of Russian patients with intellectual disability.
AB  - The use of array comparative genomic hybridization (array CGH) as a diagnostic
      tool in molecular genetics has facilitated the identification of many new
      microdeletion/microduplication syndromes (MMSs). Furthermore, this method has
      allowed for the identification of copy number variations (CNVs) whose pathogenic
      role has yet to be uncovered. Here, we report on our application of array CGH for
      the identification of pathogenic CNVs in 79 Russian children with intellectual
      disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy
      number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and
      17 were not associated with previously described syndromes. In this report, we
      describe our findings and comment on genes potentially associated with ID that
      are located within the CNV regions. 

PMID- 24291027
TI  - Characterization of GHRs, IGFs and MSTNs, and analysis of their expression
      relationships in blunt snout bream, Megalobrama amblycephala.
AB  - In order to test the hypothesis that the expression levels of GH/IGF axis genes
      would be negatively related to the expression of the myostatin genes in fish
      species, we cloned six growth regulating genes including growth hormone receptors
      1/-2 (GHRs), insulin-like growth factors-I/-II (IGFs) and myostatins-a/-b (MSTNs)
      from blunt snout bream (Megalobrama amblycephala). The contents of mRNA
      transcripts for the six genes were determined in the different tissues of adult
      and developmental stages for the embryonic and larval periods. The results of
      quantitative real-time PCR showed that GHRs, IGFs and MSTNs were widely expressed
      in the tissues we tested, with the relatively lower expression levels in
      mesonephros, gonad and spleen for the six genes. The analysis of expression
      correlation coefficients among these six genes showed that GHR 1, GHR 2 and MSTN
      b were correlated with each other in adult tissues (P<0.01). For the
      developmental stages, GHR 1 had a similar expression pattern to GHR 2 during the
      examined periods, both with the highest expression levels at 160 hpf (hours post
      fertilization) (P<0.05). IGF-II had higher expression levels than that of IGF-I
      before 400 hpf (P<0.05), while IGF-I was active after 52 hpf. The maximum of MSTN
      a and MSTN b mRNA levels were at 24 hpf and 400 hpf, respectively. The analysis
      of expression correlation coefficients showed that GHR 1, GHR 2, IGF-I, IGF-II
      and MSTN b were positively correlated with each other during embryonic
      development (P<0.01). The results from this study suggested that the relationship
      between GH/IGF axis genes and MSTNs was complex and not absolutely negative
      correlated in fish species.

PMID- 24291028
TI  - Heterologous expression of an uncharacterized universal stress protein gene
      (SbUSP) from the extreme halophyte, Salicornia brachiata, which confers salt and
      osmotic tolerance to E. coli.
AB  - Salicornia brachiata is an extreme halophyte considered to be a rich source of
      stress responsive genes and an EST database revealed that 30% of its genes are
      uncharacterized. In order to ascertain its function, a gene (Sal-E-56) of unknown
      function was made full length using RACE, cloned and characterized. The full
      length gene (873 bp; accession no. KF164282) contained an open reading frame
      (ORF) of 486 bp encoding for a protein that belongs to the universal stress
      protein (USP) family that was named SbUSP. The SbUSP interacted with adenosine
      monophosphate and exhibited characteristic motifs, phosphorylation, glycosylation
      and ATP binding sites. Further, in-silico analyses suggested a probable role in
      metabolic process of phosphate-containing compounds including signal
      transduction. In planta transcript profiling exhibited a significant expression
      response (7.8-fold) to salt stress, additionally abundant of SbUSP transcripts
      were observed during drought, heat and cold stress, reaching a maximum increase
      of 3.66-, 2.64- and 2.14-fold, respectively, at 12 or 24h. The heterologous
      expression of this gene in Escherichia coli provided enhanced stress tolerance
      and recombinant cells have higher growth rate compared to vector alone and showed
      growth at up to a 10(-5) dilution in the spot assay. It was predicted that SbUSP
      may be directly involved in tolerance mechanisms or function as a molecular
      switch (signaling molecule) to activate the stress adaptive mechanisms. However,
      further investigation will be required to determine its role as a molecular
      switch and mode of action during stress.

PMID- 24291030
TI  - Functionally distinct gene classes as bigger or smaller transcription factor
      traps: a possible stochastic component to sequential gene expression programs in
      cancer.
AB  - In cancer biology, most molecular regulatory mechanisms are casually treated as
      on/off switches for specific cancer hallmarks, despite the lack of compelling
      evidence that cancer hallmarks can be exclusively attributed to specific
      regulatory proteins. To consider a novel paradigm for the basis of regulating a
      set of effector genes for proliferation, versus apoptosis-effector genes, we used
      a bioinformatics approach to ascertain differences between the transcription
      factor binding site occurrences in the two sets of genes. Results indicated that
      there are more binding sites per gene, for transcription factors that regulate
      both proliferation and apoptosis, among the proliferation-effector genes than
      among the apoptosis-effector genes. Proliferation-effector genes also had more
      open chromatin regions. We also applied this paradigm to the question of why p53
      and interferon regulatory factor-1 (IRF-1) first activate cell cycle arrest genes
      followed by apoptosis genes, with results indicating the cycle arrest genes are
      bigger p53 and IRF-1 traps. These data support the idea that, as a set of
      transcription factors becomes active, there is a stochastic component leading to
      the accumulation of these transcription factors on genes that effect an initial
      phenotype before their accumulation on genes that effect a subsequent phenotype. 

PMID- 24291029
TI  - Association analysis of ERBB2 amplicon genetic polymorphisms and STARD3
      expression with risk of gastric cancer in the Chinese population.
AB  - The purpose of this study was to investigate whether risk of gastric cancer (GC)
      was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on
      the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We
      detected twenty-six SNPs in this gene cluster containing steroidogenic acute
      regulatory-related lipid transfer domain containing 3 (STARD3), protein
      phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1
      like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2
      (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA
      topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls
      by Sequenom. We found no associations between genetic variations and GC risk.
      However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882,
      rs881844, rs11869286 and rs1877031) conferred a protective effect on the
      susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals
      [95% CI]=0.643-0.992). The STARD3 rs1877031 TC genotype endued histogenesis of
      gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021,
      OR=2.882, 95% CI=1.173-7.084). We examined the expression of STARD3 in 243 tumor
      tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using
      immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression
      of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues
      and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001),
      tumor location (P=0.007), histological type (P=0.005) and differentiation
      (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of
      STARD3 might affect GC susceptibility. STARD3 expression might be related to the
      tumorigenesis of GC in the Chinese population.

PMID- 24291031
TI  - Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid
      levels in an older adult/elderly cohort.
AB  - BACKGROUND AND AIMS: The characterization of candidate gene polymorphisms in
      elderly populations is an important tool for the identification of risk factors
      for age-related diseases and conditions. We aimed to genotype the APOE
      polymorphisms (rs429358 and rs7412), rs61886492 (1561C>T) and rs202720 of GCPII
      gene and rs3918242 (-1562C>T) of MMP9 gene in an older-adult/elderly cohort from
      Cuiaba city, Mato Grosso Brazil as well as to characterize risk factors for
      morbidities and conditions affecting this cohort. METHODS: The studied population
      consisted of 570 subjects from Cuiaba city, Brazil, who were subjected to
      clinical interviews and blood collection for laboratory examinations and DNA
      extraction. Restriction Fragment Length Polymorphism Polymerase Chain Reaction
      (RFLP-PCR), sequence-specific primer PCR (SSP-PCR) and TaqMan(r) allelic
      discrimination assay were used for genotyping. RESULTS: The frequencies of APOE
      epsilon2 and epsilon4 were 6.6% and 14.8%, respectively, and the frequencies of
      GCPII rs61886492 T allele, GCPII rs202720 C allele and MMP9 rs3918242 T allele
      were, respectively, 3.0%, 26.6% and 10.1%. Significant associations between APOE
      epsilon2 allele with lower total cholesterol and LDL-cholesterol were found. In
      addition, MMP9 rs3918242 T allele was associated with higher LDL-cholesterol
      levels, suggesting a link between lipid metabolism alteration and cardiovascular
      disease. CONCLUSIONS: The present findings contributed to characterize risk
      factors specific for the studied population and to better understand the
      molecular physiopathology of common morbidities and conditions affecting older
      adult/elderly people.

PMID- 24291032
TI  - Evaluation of hemostatic activity of latex from three Euphorbiaceae species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Latices from several plant species of
      Euphorbiaceae family have been traditionally applied over fresh cuts to stop
      bleeding and subsequently applied over wounds to enhance healing process. The
      latex arrested bleeding from fresh wounds by reducing bleeding and whole blood
      coagulation time which are important indices of hemostatic activity. It has been
      accepted that hemostatic activity is due to the proteolytic fraction of plant
      latices. Thus, the present study aimed to assess the clot inducing properties of
      three Euphorbiaceae plants viz., Euphorbia nivulia Buch.-Ham., Pedilanthus
      tithymaloides (L.) Poit and Synadenium grantii Hook F. MATERIALS AND METHODS: In
      the present study, various proteolytic activities namely protease, gelatinase,
      milk clotting and whole blood clotting assay of the enzyme fraction of latices of
      Euphorbia nivulia, Pedilanthus tithymaloides and Synadenium grantii have been
      investigated. The inhibition profile of protease specific inhibitors was
      assessed. Also, the effects of protein fractions were studied using
      bleeding/clotting time test of fresh experimentally-induced wounds in mice.
      RESULTS: Euphorbia nivulia latex protease has noticeable blood clotting activity
      followed by Pedilanthus tithymaloides and Synadenium grantii. Stem latex protease
      of Pedilanthus tithymaloides exhibits superior procoagulant activity in different
      mammal's blood samples viz., Capra hircus, Bubalus bubalis, Ovibos moschatus and
      Bos indicus. Blood sample of ox was the most sensitive to latex protease than
      other mammal's blood. Concomitantly, the plant latex protease could significantly
      reduce whole blood clotting time of human and mice blood samples. CONCLUSION: The
      protease fraction of latices of Euphorbia nivulia, Pedilanthus tithymaloides and
      Synadenium grantii possesses phytoconstituents capable of arresting wound
      bleeding, and accelerating whole blood coagulation process. It suggests good
      potentiality for use of latex proteases in wound management. Also, the finding of
      this study showed that the protease enzyme of Pedilanthus tithymaloides has the
      most potent hemostatic agent.

PMID- 24291033
TI  - Longitudinal construct validity and responsiveness of measures of walking
      capacity in individuals with lumbar spinal stenosis.
AB  - BACKGROUND CONTEXT: Walking capacity is a primary outcome indicator for
      individuals with lumbar spinal stenosis (LSS). Therefore, there is a demand for
      psychometrically sound measures of walking that are responsive to change.
      PURPOSE: The primary objective of this study was to examine longitudinal
      construct validity of the Physical Function Scale of the Swiss Spinal Stenosis
      Questionnaire (PF Scale), the Oswestry Disability Index (ODI), and the walking
      capacity items from these scales specifically for the assessment of walking
      capacity in LSS using the objective Self-Paced Walking Test (SPWT) as the
      external standard. A secondary objective was to examine responsiveness of
      measures of walking using a self-reported walking capacity change scale as the
      external criterion standard. STUDY DESIGN: Patients were prospectively enrolled.
      PATIENT SAMPLE: Twenty-six patients were included in this study (17 women and 9
      men), with an average age of 68.5 years (SD, 9.2). All participants had LSS
      diagnosed by a spine specialist surgeon based on both clinical examination and
      imaging, as well as self-reported walking limitations (neurogenic claudication).
      OUTCOME MEASURES: The self-reported outcome measures included in this study were
      PF Scale, ODI, and self-reported walking capacity change score. FUNCTIONAL
      MEASURES: The functional measure used in the study was SPWT. METHODS:
      Longitudinal construct validity was assessed using the correlational method.
      Internal responsiveness was examined using Guyatt responsiveness index and
      external responsiveness using receiver operating characteristic analysis. Change
      in the SPWT and the self-reported walking capacity change score were used as
      external criteria for the analysis. RESULTS: The highest correlations with change
      in the SPWT were 0.78 for the ODI walking item and 0.78 for the walking capacity
      change score. Changes in the PF Scale and ODI score were correlated with change
      in the criterion SPWT at r=0.56 and r=0.70, respectively. There were no
      differences observed between the PF Scale and ODI for any of the responsiveness
      indices. CONCLUSIONS: The PF Scale, ODI, and walking capacity change score are
      able to detect changes in walking capacity in people with LSS. The individual
      walking capacity item from the ODI appears to be the most valid and responsive to
      changes in measured walking and may be a reasonable alternative for measuring
      walking when an objective test such as the SPWT is not feasible.

PMID- 24291034
TI  - Trends in the surgical treatment for spinal metastasis and the in-hospital
      patient outcomes in the United States from 2000 to 2009.
AB  - BACKGROUND CONTEXT: Surgical treatment for spinal metastasis is still
      controversial. However, with the improvements in treatment for primary tumors,
      the survival rate of patients with spinal metastasis is enhanced. At the same
      time, surgical technique for spinal metastasis has also improved. PURPOSE: The
      purpose of this study was to examine trends in the surgical treatment for spinal
      metastasis and in-hospital patient outcomes on a national level. STUDY
      DESIGN/SETTING: This was an epidemiologic study using national administrative
      data from the Nationwide Inpatient Sample (NIS) database. PATIENT SAMPLE: All
      discharges in the NIS with a diagnosis code of secondary malignant neoplasm of
      the spinal cord/brain, meninges, or bone who also underwent spinal surgery from
      2000 to 2009 were included. OUTCOME MEASURES: Trends in the surgical treatment
      for spinal metastasis, in-hospital complications and mortality, and resource use
      were analyzed. METHODS: The NIS was used to identify patients who underwent
      surgical treatment for spinal metastasis from 2000 to 2009, using the
      International Classification of Diseases, Ninth revision, Clinical Modification
      codes. Trends in the surgical treatment for spinal metastasis and in-hospital
      patient outcomes were analyzed. RESULTS: From 2000 to 2009, there was an
      increasing trend in the population growth-adjusted rate of surgical treatment for
      spinal metastasis (1.15-1.77 per 100,000; p<.001). Average Elixhauser comorbidity
      score increased over time (2.6-3.8; p<.001), and the overall in-hospital
      complication rate increased over time (14.8%-27.7%; p<.001), whereas in-hospital
      mortality rate and length of hospital stay remained stable over time (5.2%-4.6%,
      p=.413; 10.6-10.8 days, p=.626). Inflation-adjusted mean hospital charges
      increased more than two-fold over time ($50,390-$110,173; p<.001). CONCLUSIONS:
      During the last decade, surgical treatment for spinal metastasis has increased in
      the United States. The overall in-hospital complication rate and hospital charges
      increased, whereas the in-hospital mortality rate and length of hospital stay
      remained stable.

PMID- 24291035
TI  - Interaction of anticancer reduced Schiff base coumarin derivatives with human
      serum albumin investigated by fluorescence quenching and molecular modeling.
AB  - The specific binding of five reduced Schiff base derived 7-amino-coumarin
      compounds with antitumor activity to human serum albumin, the principal binding
      protein of blood, was studied by fluorescence spectroscopy. Their conditional
      binding constants were computed and the reversible binding at the Sudlow's site I
      was found to be strong (KD~0.03-2.09 MUM). Based on the data albumin can provide
      a depot for the compounds and is responsible for their biodistribution and
      transport processes. The experimental data is complemented by protein-ligand
      docking calculations for two representatives which support the observations. The
      proton dissociation constants of the compounds were also determined by UV-Vis
      spectrophotometric and fluorometric titrations to obtain the actual charges and
      distribution of the species in the various protonation states at physiological
      pH.

PMID- 24291036
TI  - A systematic review of neurodevelopmental effects of prenatal and postnatal
      organophosphate pesticide exposure.
AB  - Agricultural and residential use of organophosphate (OP) pesticides has increased
      in recent decades after banning some persistent pesticides. Although there is
      evidence of the effects of OPs on neurodevelopment and behaviour in adults,
      limited information is available about their effects in children, who might be
      more vulnerable to neurotoxic compounds. This paper was aimed at analysing the
      scientific evidence published to date on potential neurodevelopmental and
      behavioural effects of prenatal and postnatal exposure to OPs. A systematic
      review was undertaken to identify original articles published up to December 2012
      evaluating prenatal or postnatal exposure to OPs in children and effects on
      neurodevelopment and/or behaviour. Articles were critically compared, focusing on
      the methodology used to assess exposure and adverse effects, as well as potential
      contributing factors that may modify both exposure and outcomes, such as genetic
      susceptibility to certain enzymes involved in OPs metabolisation (e.g.
      paraoxonase-1) and gender differences. Twenty articles met the inclusion
      criteria, 7 of which evaluated prenatal exposure to OPs, 8 postnatal exposure and
      5 both pre- and postnatal exposure. Most of the studies evaluating prenatal
      exposure observed a negative effect on mental development and an increase in
      attention problems in preschool and school children. The evidence on postnatal
      exposure is less consistent, although 2 studies found an increase in reaction
      time in schoolchildren. Some paraoxonase-1 polymorphisms could enhance the
      association between OPs exposure and mental and psychomotor development. A large
      variability in epidemiological designs and methodologies used for assessing
      exposure and outcome was observed across the different studies, which made
      comparisons difficult. Prenatal and to a lesser extent postnatal exposure to OPs
      may contribute to neurodevelopmental and behavioural deficits in preschool and
      school children. Standardised methodologies are needed to allow results to be
      better compared and to perform a quantitative meta-analysis before drawing any
      final conclusions. 

PMID- 24291037
TI  - Interaction of polyacrylic acid coated and non-coated iron oxide nanoparticles
      with human neutrophils.
AB  - Iron oxide nanoparticles (ION), with different coatings and sizes, have attracted
      extensive interest in the last years to be applied in drug delivery, cancer
      therapy and as contrast agents in imagiologic techniques such as magnetic
      resonance imaging. However, the safety of these nanoparticles is still not
      completely established, particularly to host defense systems that are usually
      recruited for their clearance from the body. In this paper, given the importance
      of neutrophils in the immune response of the organism to nanoparticles, the
      effect of polyacrylic acid (PAA)-coated and non-coated ION on human neutrophils
      was evaluated in vitro, namely their capacity to activate the oxidative burst and
      to modify their lifespan. The obtained results showed that the studied PAA-coated
      and non-coated ION triggered neutrophils' oxidative burst in a NADPH oxidase
      dependent manner, and that PAA-coated ION increased - while non-coated ION
      prevented - apoptotic signaling and apoptosis. These effects may have important
      clinical implications in biomedical applications of ION. 

PMID- 24291038
TI  - Cytoplasmic p21(CIP1/WAF1), ERK1/2 activation, and cytoskeletal remodeling are
      associated with the senescence-like phenotype after airborne particulate matter
      (PM(10)) exposure in lung cells.
AB  - The exposure to particulate matter with a mean aerodynamic diameter <=10 MUm
      (PM10) from urban zones is considered to be a risk factor in the development of
      cancer. The aim of this work was to determine if PM10 exposure induces factors
      related to the acquisition of a neoplastic phenotype, such as cytoskeletal
      remodeling, changes in the subcellular localization of p21(CIP1/WAF1), an
      increase in beta-galactosidase activity and changes in cell cycle. To test our
      hypothesis, PM10 from an industrial zone (IZ) and a commercial zone (CZ) were
      collected, and human adenocarcinoma lung cell cultures (A549) were exposed to a
      sublethal PM10 concentration (10 MUg/cm(2)) for 24 h and 48 h. The results showed
      that PM10 exposure induced an increase in F-actin stress fibers and caused the
      cytoplasmic stabilization of p21(CIP1/WAF1) via phosphorylation at Thr(145) and
      Ser(146) and the phosphorylation of ERK1/2 on Thr(202). Changes in the cell cycle
      or apoptosis were not observed, but an increase in beta-galactosidase activity
      was detected. The PM10 from CZ caused more dramatic effects in lung cells. We
      conclude that PM10 exposure induced cytoplasmic p21(CIP1/WAF1) retention, ERK1/2
      activation, cytoskeleton remodeling and the acquisition of a senescence-like
      phenotype in lung cells. These alterations could have mechanistic implications
      regarding the carcinogenic potential of PM10.

PMID- 24291040
TI  - Synthesis and preliminary evaluation of a new fluorine-18 labelled triazine
      derivative for PET imaging of cannabinoid CB2 receptor.
AB  - Cannabinoid CB2 PET tracers are considered as a promising alternative to PBR/TSPO
      tracers for the in-vivo imaging of neuroinflammation. We describe here the
      synthesis and characterization of compound 3, a new potent and brain penetrating
      CB2 ligand based on an original triazine template. The PET tracer [(18)F]
      dideutero-3 was prepared in a three steps radiosynthesis, and demonstrated
      significant uptake in rhesus macaque and baboon brain with a maximum SUV of about
      0.7-0.9g/mL, followed by a moderate washout over time. 

PMID- 24291039
TI  - The combination of proteasome inhibitors bortezomib and gambogic acid triggers
      synergistic cytotoxicity in vitro but not in vivo.
AB  - The proteasome inhibitor-based combinational therapy has been reported to be an
      efficient cancer treatment. Our recent studies demonstrated that the natural
      compound gambogic acid (GA) is a tissue-specific proteasome inhibitor, comparable
      to bortezomib (Bor), and sensitizes malignant cells to the proteasome inhibitor
      MG132/MG262 both in vitro and in vivo. The aim of this study was to further
      extend our investigation by combining GA with the clinically used proteasome
      inhibitor Bor to test their combined efficacy against human hepatoma HepG2 and
      mouse hepatoma H22 cells. GA and Bor synergistically induced cytotoxicity and
      cell death in human HepG2 and mouse H22 cells, and accelerated proteasome
      inhibition, endoplasmic reticulum (ER) stress and caspase activation in HepG2
      cancer cells. However, unexpectedly, GA did not enhance or even antagonized Bor
      induced tumor growth inhibition in H22 allograft and HepG2 xenograft tumor
      models. These findings demonstrated that GA increased Bor activity in vitro but
      limited the efficacy of Bor in vivo. We suggest that the combination of GA and
      Bor be avoided when administering these drugs to patients. 

PMID- 24291041
TI  - Discovery and optimization of Lu AF58801, a novel, selective and brain penetrant
      positive allosteric modulator of alpha-7 nicotinic acetylcholine receptors:
      attenuation of subchronic phencyclidine (PCP)-induced cognitive deficits in rats
      following oral administration.
AB  - In this Letter, we describe a chemical lead optimization campaign starting from a
      novel, weak alpha7 nicotinic acetylcholine receptor positive allosteric modulator
      (PAM) hit from a HTS screen. Exploration of the structure-activity relationships
      for alpha7 PAM potency, intrinsic hepatic clearance, the structure-property
      relationships for lipophilicity, and thermodynamic solubility, led to the
      identification of Lu AF58801: a potent, orally available, brain penetrant PAM of
      the alpha7 nicotinic acetylcholine receptor, showing efficacy in a novel object
      recognition task in rats treated subchronically with phencyclidine (PCP). 

PMID- 24291042
TI  - Synthesis, anti-HIV activity, integrase enzyme inhibition and molecular modeling
      of catechol, hydroquinone and quinol labdane analogs.
AB  - Labdane analogs with o-quinol, catechol and hydroquinone moiety have been
      synthesized using Diels-Alder reaction of methyl 3,4-dioxocyclohexa-1,5-diene
      carboxylate, 3,4-dioxocyclohexa-1,5-diene-carboxylic acid and 3,6-dioxocyclohexa
      1,4-dienecarboxylic acid with mono terpene 1,3-dienes, namely ocimene and
      myrcene. The resulting molecules and their derivatives were evaluated for their
      anti-HIV-1 activity using TZM-bl cell based virus infectivity assay. Two
      molecules 13 and 18 showed anti-HIV activity with IC50 values 5.0 (TI=11) and 4.6
      (TI=46)MUM, respectively. The compounds 17, 18 and 20 showed efficacy against HIV
      1 integrase activity and showed inhibition with IC50 13.4, 11.1 and 11.5MUM,
      respectively. The HIV-1 integrase inhibition activity of these synthetic
      molecules was comparable with integric acid, the natural fungal metabolite.
      Molecular modeling studies for the HIV-1 integrase inhibition of these active
      synthetic molecules indicated the binding to the active site residues of the
      enzyme. 

PMID- 24291044
TI  - Relationship of scapular neck length to scapular notching after reverse total
      shoulder arthroplasty by use of plain radiographs.
AB  - BACKGROUND: Scapular notching in reverse shoulder arthroplasty appears to be a
      multifactorial problem related to both implant and patient factors. There are
      well-established guidelines for implant position. Recent cadaveric studies have
      illustrated anatomic factors that need further consideration. Scapular neck
      length and inferior glenoid tubercle morphology may be major factors predicting
      scapular notching. METHODS: From 2 institutions, we reviewed 3 years of patient
      radiographs for reverse shoulder arthroplasty, including all reverse shoulder
      arthroplasties at least 12 months from surgery. We used true anterior-posterior
      radiographs, both preoperatively and postoperatively, and focused on the "ideal"
      positioning of the glenosphere: at or below the inferior margin of the glenoid,
      and neutral or slight inferior tilt. Radiographs were reviewed by 2 independent
      surgeons. Glenoid articular surface height was measured along with scapular neck
      length and notching presence. RESULTS: Of 64 sets of radiographs reviewed, 50 met
      inclusion criteria. Notching was present in only 25 (50%) of the sets. The mean
      scapular neck length was 8.9 mm with a neck:surface ratio of 0.23 in the notching
      present group and 12.1 mm with a neck:surface ratio of 0.32 in the notching
      absent group. Significance was reached with both scapular neck length and
      neck:surface ratio (P = .0012 and P = .0006, respectively). CONCLUSIONS: There is
      a high degree of significance that patient anatomy does play a role in the
      occurrence of notching. Surgeons may consider lateralizing the glenosphere in
      patients with a scapular neck length of less than 9 mm measured on a true
      anteroposterior radiograph. LEVEL OF EVIDENCE: Anatomy study, imaging.

PMID- 24291043
TI  - Restoration of lung surfactant protein D by IL-6 protects against secondary
      pneumonia following hemorrhagic shock.
AB  - OBJECTIVES: To identify novel approaches to improve innate immunity in the lung
      following trauma complicated by hemorrhagic shock (T/HS) for prevention of
      nosocomial pneumonia. METHODS: We developed a rat model of T/HS followed by
      Pseudomonas aeruginosa (PA) pneumonia to assess the effect of alveolar epithelial
      cell (AEC) apoptosis, and its prevention by IL-6, on lung surfactant protein (SP)
      D protein levels, lung bacterial burden, and survival from PA pneumonia, as well
      as to determine whether AEC apoptosis is a consequence of the unfolded protein
      response (UPR). Lung UPR transcriptome analysis was performed on rats subjected
      to sham, T/HS, and T/HS plus IL-6 protocols. Group comparisons were performed via
      Kaplan-Meier or ANOVA. RESULTS: T/HS decreased lung SP-D by 1.8-fold (p < 0.05),
      increased PA bacterial burden 9-fold (p < 0.05), and increased PA pneumonia
      mortality by 80% (p < 0.001). IL-6, when provided at resuscitation, normalized SP
      D levels (p < 0.05), decreased PA bacterial burden by 4.8-fold (p < 0.05), and
      prevented all mortality from PA pneumonia (p < 0.001). The UPR transcriptome was
      significantly impacted by T/HS; IL-6 treatment normalized the T/HS-induced UPR
      transcriptome changes (p < 0.05). CONCLUSIONS: Impaired innate lung defense
      occurs following T/HS and is mediated, in part, by reduction in SP-D protein
      levels, which, along with AEC apoptosis, may be mediated by the UPR, and
      prevented by use of IL-6 as a resuscitation adjuvant.

PMID- 24291045
TI  - Three-dimensional humeral morphologic alterations and atrophy associated with
      obstetrical brachial plexus palsy.
AB  - BACKGROUND: Obstetrical brachial plexus palsy (OBPP) is a common birth injury,
      resulting in severe functional losses. Yet, little is known about how OBPP
      affects the 3-dimensional (3D) humeral morphology. Thus, the purpose of this
      study was to measure the 3D humeral architecture in children with unilateral
      OBPP. METHODS: Thirteen individuals (4 female and 9 male patients; mean age, 11.8
      +/- 3.3 years; mean Mallet score, 15.1 +/- 3.0) participated in this
      institutional review board approved study. A 3D T1-weighted gradient-recalled
      echo magnetic resonance image set was acquired for both upper limbs (involved and
      noninvolved). Humeral size, version, and inclination were quantified from 3D
      humeral models derived from these images. RESULTS: The involved humeral head was
      significantly less retroverted and in declination (medial humeral head pointed
      anteriorly and inferiorly) relative to the noninvolved side. Osseous atrophy was
      present in all 3 dimensions and affected the entire humerus. The inter-rater
      reliability was excellent (intraclass correlation coefficient, 0.96-1.00).
      DISCUSSION: This study showed that both humeral atrophy and bone shape
      deformities associated with OBPP are not limited to the axial plane but are 3D
      phenomena. Incorporating information related to these multi-planar, 3D humeral
      deformities into surgical planning could potentially improve functional outcomes
      after surgery. The documented reduction in retroversion is an osseous adaptation,
      which may help maintain glenohumeral congruency by partially compensating for the
      internal rotation of the arm. The humeral head declination is a novel finding and
      may be an important factor to consider when one is developing OBPP management
      strategies because it has been shown to lead to significant supraspinatus
      inefficiencies and increased required elevation forces.

PMID- 24291046
TI  - Medial grasping sutures significantly improve load to failure of the rotator cuff
      suture bridge repair.
AB  - BACKGROUND: The suture bridge (SB) transosseous-equivalent rotator cuff repair
      reduces re-tear rates compared with single-row or other double-row constructs.
      However, failure rates continue to be high, especially in large and massive
      tears. The aim of this study was to assess the biomechanical performance of a new
      SB repair with use of a medial grasping suture compared with the traditional SB
      repair. METHODS: Seven matched pairs of sheep infraspinatus tendons were randomly
      assigned to either SB or suture bridge with grasping suture (SBGS) repair. Each
      construct was subjected to cyclic loading and then loaded until failure under
      displacement control in a materials testing machine. Footprint displacement,
      ultimate load to failure, and mode of failure were assessed. RESULTS: The rotator
      cuff footprint displacement was less during tensile loading with the addition of
      the medial grasping suture. The ultimate load to failure was significantly
      greater for the SBGS repair group than for the SB repair group (334.0 N vs 79.8
      N). The mode of failure was the tendon pulling off the footprint in all cases
      (type 1 tear). There were no failures in which the tendon tore at the medial row
      of anchors, leaving part of the tendon still on the footprint (type 2 tear).
      CONCLUSION: The addition of a medial grasping suture significantly improved the
      ultimate load to failure and reduced the footprint displacement of the SB rotator
      cuff repair in a biomechanical model.

PMID- 24291047
TI  - Proximal humerus nailing: a randomized clinical trial between curvilinear and
      straight nails.
AB  - BACKGROUND: Intramedullary nailing of displaced proximal humerus fractures is an
      attractive option in the elderly patient. However, in recent reports, some
      existing intramedullary nails have shown high rate of complications, so new
      designs are being developed. The objective of the present study is to report on
      outcomes and complications when comparing a straight to a curvilinear nail
      design. METHODS: We prospectively include 54 patients with Neer's 2- or 3-part
      proximal humerus fractures. Two were lost to follow-up, 26 were surgically
      treated with a new straight humeral nail (MultiLoc, Synthes) mean age 69 (range,
      47-87 years), and 26 with a curvilinear nail (Polarus, Acumed) mean age 71
      (range, 38-89 years). At final follow-up (average 14 months), patients underwent
      a clinical and radiographic evaluation. Clinical outcome was assessed with the
      adjusted Constant score. RESULTS: All but 1 fracture went on to radiographic
      union. Mean Constant score in the Polarus nail was 72.7 +/- 16.0 and 83.3 +/-
      16.7 in the MultiLoc (P = .246). Symptoms related with rotator cuff disease were
      present in 19/26 patients (73%) and in 9/26 (34.6%), respectively (P = .001). The
      mean neck-shaft angle at final follow-up was 135 degrees  in the MultiLoc group
      and 130 degrees  in the Polarus group (P > .05). Reoperation rate was 42% for
      Polarus and 11.5% for MultiLoc. CONCLUSION: Straight intramedullary nails had a
      comparable union rate to an accepted curvilinear design, with a much lower
      incidence of complications. Rotator cuff pain and dysfunction can be minimized
      with the use of newer generation straight nails.

PMID- 24291048
TI  - Prostaglandin E2 elicits greater bronchodilation than salbutamol in mouse
      intrapulmonary airways in lung slices.
AB  - BACKGROUND: Current asthma therapy may not adequately target contraction of
      smaller intrapulmonary airways, which are a major site of airway obstruction and
      inflammation. The aim of this study was to characterise responses of mouse
      intrapulmonary airways to prostaglandin E(2) (PGE(2)) and compare its dilator
      efficacy with the beta(2)-adrenoceptor agonist salbutamol in situ, using lung
      slices. METHODS: Lung slices (150 MUm) were prepared from male Balb/C mice.
      Changes in intrapulmonary airway lumen area were recorded and analysed by phase
      contrast microscopy. Relaxation to PGE(2) and salbutamol were assessed following
      various levels of pre-contraction with methacholine, serotonin or endothelin-1,
      as well as following overnight incubation with PGE(2) or salbutamol. The
      mechanism of PGE(2)-mediated relaxation was explored using selective EP
      antagonists (EP(1/2) AH6809; EP(4) L-161982) and Ca(2+)-permeabilized slices,
      where airway responses are due to regulation of Ca(2+)-sensitivity alone.
      RESULTS: PGE2 elicited EP(1/2)-mediated relaxation of intrapulmonary airways.
      PGE(2) was more potent than salbutamol in opposing submaximal pre-contraction to
      all constrictors tested, and only PGE(2) opposed maximal pre-contraction with
      endothelin-1. Relaxation to PGE(2) was maintained when contraction to
      methacholine was mediated via increased Ca(2+)-sensitivity alone. PGE(2) was less
      sensitive to homologous or heterologous desensitization of its receptors than
      salbutamol. CONCLUSION: The greater efficacy and potency of PGE(2) compared to
      salbutamol in mouse intrapulmonary airways supports further investigation of the
      mechanisms underlying this improved dilator responsiveness for the treatment of
      severe asthma.

PMID- 24291049
TI  - Sample and data sharing: observations from a central data repository.
AB  - OBJECTIVES: From 2003 to 2013, RTI International served as the data repository
      for the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK).
      RTI worked closely with two sample repository partners to build and maintain the
      Central Repository (CR) that made data and samples available to approved
      requestors. In this paper, we recap aspects of establishing the mechanism; detail
      the challenges and limitations of data and sample sharing, and explore the future
      of resource sharing in light of the evolving environment of research funding.
      DESIGN AND METHODS: Effective maintenance required the system to be flexible and
      dynamic while at the same time compliant with established data standards.
      RESULTS: Our years serving as the CR for NIDDK have yielded a number of
      observations about the difficulties of running a repository, an operation that is
      by definition dependent on many outside parties whose degree of expertise and
      efficiency have a direct impact on repository functioning. CONCLUSION: The bio
      banking industry will likely continue to become more globally centralized for
      studying specific genetic diseases and monitoring the health of our environment.
      The dynamic relationship between emerging technologies and the infrastructure
      will be needed to support future research that requires the ability of
      organizations providing support to remain flexible even while following
      established standards.

PMID- 24291050
TI  - Association of glutathione-S-transferase gene polymorphism and lipoprotein
      subclasses in hemodialysis patients.
AB  - OBJECTIVES: End-stage renal disease (ESRD) is characterized by profound
      dyslipidemia and enhanced oxidative stress. The patients also show evidence of
      exhausted and/or deficient anti-oxidative defense enzymes, one of them being
      glutathione-S-transferase (GST). This study investigates relationship between GST
      gene polymorphism and low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) subclasses in ESRD. DESIGN AND METHODS: GSTM1, T1, and P1 genotypes were
      determined by polymerase chain reaction-restriction fragment length polymorphism
      in 160 patients undergoing hemodialysis. LDL and HDL subclasses were separated by
      gradient gel electrophoresis and biochemical parameters were measured by routine
      laboratory methods. RESULTS: GSTM1-positive patients had higher proportion of
      small, dense LDL III particles than those with GSTM1-null genotype (P<0.05).
      Similarly, GSTP1-Ile/Ile patients had higher proportion of LDL III (P<0.05), but
      more HDL 2b and less HDL 3a particles than GSTP1-Ile/Val and Val/Val carriers
      (P<0.05). LDL subclass distribution in smokers with GSTM1-null genotype was
      shifted towards smaller particles, as compared to GSTM1-positive and GSTM1-null
      non-smokers. Smokers with GSTP1-Ile/Val and Val/Val genotypes had smaller LDL
      size than their non-smoking counterparts (P<0.05). Both smokers and non-smokers
      with GSTP1 Ile/Ile genotype had more LDL III particles than non-smokers carrying
      Val allele. Non-smokers with GSTP1 Ile/Ile genotype had more HDL 2b subclasses
      than non-smokers with GSTP1-Ile/Val and Val/Val (P<0.05), but less HDL 3a
      particles than smokers with GSTP1-Ile/Val and Val/Val genotypes (P<0.05). GSTT1
      gene polymorphism had no effect on lipoprotein subclass distributions.
      CONCLUSIONS: Our results demonstrate significant associations between low
      activity GST genotypes and proatherogenic lipoprotein particles in hemodialysis
      patients which might further increase their cardiovascular disease risk.

PMID- 24291051
TI  - Multisite evaluation of a monoclonal IMMULITE erythropoietin immunoassay.
AB  - BACKGROUND: Erythropoietin (EPO) measurements are useful in diagnosing anemias
      and polycythemias. We conducted a multisite evaluation of a monoclonal
      IMMULITE(r) EPO immunoassay.(1) DESIGN AND METHODS: The IMMULITE EPO assay is a
      solid-phase enzyme-labeled chemiluminescent immunometric assay. Method comparison
      to the Beckman ACCESS 2 assay using clinically characterized samples and
      reproducibility studies were conducted at three external independent
      laboratories. Internal evaluation conducted at Siemens included comparison of
      IMMULITE(r) 2000 and IMMULITE(r) 1000 assays to the ACCESS 2 assay; imprecision;
      linearity; limit of blank (LoB), limit of detection (LoD), and functional
      sensitivity; potential interference and cross-reactants; and reference interval
      determination. RESULTS: External method comparison gave Deming regression of
      (IMMULITE 2000)=0.96(ACCESS 2)+2.57IU/L, r=0.98 (n=217). Reproducibility ranged
      from 6.1% to 16.2%. Internal method comparisons gave Deming regressions of
      (IMMULITE 2000)=1.09(ACCESS 2)-3.51IU/L, r=0.98 and (IMMULITE 1000)=0.95(ACCESS
      2)+0.52IU/L, r=0.95. Total imprecision ranged from 6.4% to 10.3% and linearity
      was confirmed from 3.5 to 562IU/L. LoB, LoD, and functional sensitivity were 0.5,
      1.0, and 1.5IU/L, respectively. The assay was highly specific for EPO.
      Nonparametric reference interval was 4.3 to 29.0IU/L (n=170). CONCLUSIONS: The
      monoclonal IMMULITE EPO assay showed acceptable performance for EPO measurement.

PMID- 24291052
TI  - FoxP3 demethylation is increased in human colorectal cancer and rat
      cholangiocarcinoma tissue.
AB  - OBJECTIVES: FoxP3 expression is a marker for Tregs which are known to be involved
      in tumor immunity. We aimed to evaluate FoxP3 promoter demethylation in human
      colorectal cancer (CRC) and rat intrahepatic cholangiocarcinoma (ICC). DESIGN AND
      METHODS: Bisulfite-treated genomic DNA templates of shock frozen paired samples
      were studied from 13 anonymous CRC patients and from 10 male rats (n=6 ICC
      induced by thioacetamide and n=4 age-matched controls). Real-time PCR was carried
      out using a LightCycler 480 system. Human FoxP3 and CD3 promoter demethylations
      were estimated using previously described assays; and rat FoxP3 promoter
      demethylation using a newly developed assay. RESULTS: A significant 3.5-fold
      increase of the demethylation in FoxP3 promoter region was found in human CRC and
      rat ICC (P<0.05). The average frequency of cells with FoxP3 demethylation in
      patients suffering from CRC was 0.26% in normal tissue and 0.92% in tumor tissue
      (n=11 paired samples). Although, no significant difference was found between the
      mean frequency of CD3 demethylation in normal tissue (4.80%, n=6) and in tumor
      tissue (4.14%, n=6) from CRC patients, the ratio of demethylated CD3/FoxP3
      promoter areas was significantly lower in tumor specimens (P<0.05). Using our
      novel assay, we found a significant increase in mean frequencies of cells with
      FoxP3 demethylation in rats with ICC (7.42%, n=6) in comparison to controls
      (2.14%, n=4). CONCLUSION: FoxP3 seems to be an interesting biomarker for immune
      response to epithelial tumors. Functional consequences from the increase of Tregs
      remain to be demonstrated. Further studies with outcome data are necessary.

PMID- 24291053
TI  - A role for glutamate-333 of Saccharomyces cerevisiae cystathionine gamma-lyase as
      a determinant of specificity.
AB  - Cystathionine gamma-lyase (CGL) catalyzes the hydrolysis of l-cystathionine (l
      Cth), producing l-cysteine (l-Cys), alpha-ketobutyrate and ammonia, in the second
      step of the reverse transsulfuration pathway, which converts l-homocysteine (l
      Hcys) to l-Cys. Site-directed variants substituting residues E48 and E333 with
      alanine, aspartate and glutamine were characterized to probe the roles of these
      acidic residues, conserved in fungal and mammalian CGL sequences, in the active
      site of CGL from Saccharomyces cerevisiae (yCGL). The pH optimum of variants
      containing the alanine or glutamine substitutions of E333 is increased by 0.4-1.2
      pH units, likely due to repositioning of the cofactor and modification of the pKa
      of the pyridinium nitrogen. The pH profile of yCGL-E48A/E333A resembles that of
      Escherichia coli cystathionine beta-lyase. The effect of substituting E48, E333
      or both residues is the 1.3-3, 26-58 and 124-568-fold reduction, respectively, of
      the catalytic efficiency of l-Cth hydrolysis. The Km(l-Cth) of E333 substitution
      variants is increased ~17-fold, while Km(l-OAS) is within 2.5-fold of the wild
      type enzyme, indicating that residue E333 interacts with the distal amine moiety
      of l-Cth, which is not present in the alternative substrate O-acetyl-l-serine.
      The catalytic efficiency of yCGL for alpha,gamma-elimination of O-succinyl-l
      homoserine (kcat/Km(l-OSHS)=7+/-2), which possesses a distal carboxylate, but
      lacks an amino group, is 300-fold lower than that of the physiological l-Cth
      substrate (kcat/Km(l-Cth)=2100+/-100) and 260-fold higher than that of l-Hcys
      (kcat/Km(l-Hcys)=0.027+/-0.005), which lacks both distal polar moieties. The
      results of this study suggest that the glutamate residue at position 333 is a
      determinant of specificity. 

PMID- 24291055
TI  - Neonatal paternal deprivation impairs social recognition and alters levels of
      oxytocin and estrogen receptor alpha mRNA expression in the MeA and NAcc, and
      serum oxytocin in mandarin voles.
AB  - Paternal care is necessary for the healthy development of social behavior in
      monogamous rodents and social recognition underpins social behavior in these
      animals. The effects of paternal care on the development of social recognition
      and underlying neuroendocrine mechanisms, especially the involvement of oxytocin
      and estrogen pathways, remain poorly understood. We investigated the effects of
      paternal deprivation (PD: father was removed from neonatal pups and mother alone
      raised the offspring) on social recognition in mandarin voles (Microtus
      mandarinus), a socially monogamous rodent. Paternal deprivation was found to
      inhibit the development of social recognition in female and male offspring
      according to a habituation-dishabituation paradigm. Paternal deprivation resulted
      in increased inactivity and reduced investigation during new encounters with
      other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen
      receptor alpha (ERalpha) mRNA expression in the medial amygdala and nucleus
      accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in
      females, but had no effect on males. Our results provide substantial evidence
      that paternal deprivation inhibits the development of social recognition in
      female and male mandarin voles and alters social behavior later in life. This is
      possibly the result of altered expression of central OTR and ERalpha and serum OT
      levels caused by paternal deprivation. 

PMID- 24291054
TI  - Study of pharmacodynamic interaction of Phyllanthus emblica extract with
      clopidogrel and ecosprin in patients with type II diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is associated with oxidative stress which impairs
      the platelet function. Phyllanthus emblica extract a rich source of vitamin C
      plays an important role in scavenging free radicals. The effect of vitamin C on
      platelet aggregation in healthy and coronary artery disease patients has been
      demonstrated. The present study attempts to study the pharmacodynamic
      interactions of P. emblica extract with clopidogrel and ecosprin. MATERIALS AND
      METHODS: This was a randomized open label crossover study of 10 type II diabetic
      patients. The dosage schedules were either single dose of 500 mg P. emblica
      extract or 75 mg clopidogrel or 75 mg ecosprin or 500 mg P. emblica+75 mg
      clopidogrel or 500 mg P. emblica+75 mg ecosprin. After single dose study and
      washout period, patients received either 500 mg P. emblica extract twice daily or
      75 mg clopidogrel or 75 mg ecosprin once daily or combinations for 10 days.
      Platelet aggregation was measured at baseline and at 4h of treatment after single
      and multiple dose study along with recording of bleeding and clotting time.
      RESULTS: After single and multiple dose administration of the three treatments
      and with combinations there was statistically significant decrease of platelet
      aggregation compared to baseline. Further, the mean percent inhibition of
      platelet aggregation was significant, when compared between single and multiple
      doses of P. emblica. The bleeding and clotting time was prolonged with single and
      multiple dose administration of all treatments compared to baseline. All
      treatments were well tolerated. CONCLUSION: P. emblica extract demonstrated
      significant antiplatelet activity with both single and multiple dose
      administration.

PMID- 24291056
TI  - High throughput identification and quantification of 16 antipsychotics and 8
      major metabolites in serum using ultra-high performance liquid chromatography
      tandem mass spectrometry.
AB  - BACKGROUND: Therapeutic drug monitoring of antipsychotics is important for
      optimizing therapy, explaining adverse effects, non-response or poor compliance.
      We developed a UHPLC-MS/MS method for quantification of 16 commonly used and
      recently marketed antipsychotics and 8 metabolites in serum. METHODS: After
      liquid-liquid extraction using methyl tert-butyl ether, analysis was performed on
      an Agilent Technologies 1290 Infinity LC system coupled with an Agilent
      Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient
      elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in
      dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal
      standards were used for every compound, except for bromperidol and levosulpiride.
      RESULTS: Mean recovery was 86.8%. Matrix effects were -18.4 to +9.1%. Accuracy
      ranged between 91.3 and 107.0% at low, medium and high concentrations and between
      76.2 and 113.9% at LLOQ. Within-run precision was <15% (CV), except for asenapine
      and hydroxy-iloperidone. Between-run precision was aberrant only for 7-hydroxy-N
      desalkylquetiapine, asenapine and reduced haloperidol. No interferences were
      found. No problems of instability were observed, even for olanzapine. The method
      was successfully applied on patient samples. CONCLUSIONS: The liquid-liquid
      extraction and UHPLC-MS/MS technique allows robust target screening and
      quantification of 23 antipsychotics and metabolites.

PMID- 24291057
TI  - Molecular analysis of chylomicronemia in a clinical laboratory setting: diagnosis
      of 13 cases of lipoprotein lipase deficiency.
AB  - BACKGROUND: Familial chylomicronemia (type I hyperlipidemia) is a rare autosomal
      recessive disease due mainly to rare variants in the lipoprotein lipase (LPL)
      gene sequence. Molecular diagnosis of LPL deficiency is now a requirement for the
      first gene therapy treatment approved in the European Union. Altered coding
      sequence variants in APOC2, APOA5 or GPIHBP-1 can also cause familial
      chylomicronemia. Herein, we report the results of our molecular diagnostic
      activity in this topic, carried out in the setting of a Spanish clinical practice
      hospital laboratory, which was also extended to some patients who were more
      likely to have type V hyperlipidemia. METHODS: Samples from twenty-nine unrelated
      probands with severe hypertriglyceridemia were referred for molecular diagnosis.
      Samples were first screened for LPL sequence variants by DNA sequencing and, in
      the absence of alterations, subsequent analysis of APOC2, APOA5, and GPIHBP1
      genes was undertaken. Analysis of LPL function in vitro was further studied in
      two previously uncharacterized LPL sequence variants. RESULTS: Fourteen
      different, loss-of-function variants were found in the LPL gene: 4 were novel or
      uncharacterized allelic variants, and of these, 2 were directly shown to affect
      function. Twenty of 29 probands presented at least one LPL gene allele variant: 8
      were homozygous, 9 compound heterozygous and 3 heterozygous. In 13 probands, the
      finding of two loss-of-function variants supported the diagnosis of LPL
      deficiency. None of the probands presented sequence variants in the APOC2 gene,
      whereas 3 presented rare variants within the APOA5 gene. Four of the five
      patients heterozygous for a common variant in the GPIHBP-1 gene also carried
      APOA5 sequence variants. CONCLUSIONS: Loss-of-function LPL variants leading to
      familial chylomicronemia were found in 13 patients, accounting for a significant
      proportion of the LPL-deficient patients predicted to live in Spain.

PMID- 24291058
TI  - Release kinetics of N-terminal pro-B-type natriuretic peptide in a clinical model
      of acute myocardial infarction.
AB  - BACKGROUND: N-terminal segment of B-type natriuretic peptide prohormone (NT
      proBNP) is elevated in patients with acute myocardial infarction (AMI) thus
      providing both diagnostic information and prognostic information. The aim of the
      present study was to determine the time course of NT-proBNP release in patients
      undergoing transcoronary ablation of septal hypertrophy (TASH) a procedure
      mimicking AMI. METHODS: We analyzed the release kinetics of NT-proBNP in 18
      consecutive patients with hypertrophic obstructive cardiomyopathy undergoing
      TASH. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and
      105 min, and 2, 4, 8, and 24h after TASH. RESULTS: NT-proBNP concentrations
      showed a continuous increase during the first 75 min with a significant percent
      change compared to baseline value already 15 min after TASH (105.6% [IQR 102.2
      112.7]; P<0.001). All patients had a significant increase of NT-proBNP at 45 min
      (range of percent increase [min-max]: 103.5-137.2%; range of absolute increase
      [min-max]: 23.5-304.0 ng/L). NT-proBNP concentrations decreased below the
      baseline value until the 8th h after initiation of myocardial infarction.
      CONCLUSION: NT-proBNP concentration increases immediately after induction of
      myocardial infarction proving early evidence of myocardial injury despite the
      decrease of the left ventricular wall stress due to the TASH related reduction of
      the left ventricular outflow gradient.

PMID- 24291059
TI  - Verification of in vitro medical diagnostics (IVD) metrological traceability:
      responsibilities and strategies.
AB  - To be accurate and equivalent, laboratory results should be traceable to higher
      order references. Furthermore, their analytical performance should fulfill
      acceptable measurement uncertainty criteria defined to fit the intended clinical
      use. With this aim, In Vitro Diagnostics (IVD) manufacturers should define a
      calibration hierarchy to assign traceable values to their system calibrators and
      to fulfill during this process uncertainty limits for calibrators, which should
      represent a proportion of the uncertainty budget allowed for laboratory results.
      It is important that end-users may know and verify how manufacturers have
      implemented the traceability of their calibrators and estimated the corresponding
      uncertainty. However, full information about traceability and combined
      uncertainty of calibrators is currently not available. Important tools for IVD
      traceability surveillance are the verification by laboratories of the consistency
      of declared performance during daily operations performed in accordance with the
      manufacturer's instructions and the organization of appropriately structured
      External Quality Assessment (EQA) programs. The former activity should be
      accomplished by analyzing system control materials and confirming that current
      measurements are in the manufacturer's established control range. With regard to
      EQA, it is mandatory that target values for materials are assigned with reference
      procedures by accredited laboratories, that materials are commutable and that a
      clinically allowable inaccuracy for participant's results is defined.

PMID- 24291060
TI  - Rhythmic life of the Arctic charr: adaptations to life at the edge.
AB  - High latitudes are characterized by strong seasonal changes in environmental
      conditions, including temperature and food availability. To cope with these
      changes, many high latitude species have developed circannual oscillators that
      enable them to anticipate and prepare for forthcoming environmental changes and
      synchronize seasonal events (e.g. reproduction) to environmental fluctuations.
      The Arctic charr (Salvelinus alpinus) is the world's northernmost freshwater fish
      species with a distribution largely confined within the Arctic. In the
      northernmost part of its distribution they have developed an anadromous life
      history strategy implying annual, seaward migrations in the summer to utilize the
      rich feeding opportunity in the sea. Overwintering in freshwater is characterized
      by anorexia and energy conservation. The seaward migration in early summer is
      preceded by physiological and behavioral changes (smolting), by which they
      develop seawater tolerance (hypoosmoregulatory ability) and migratory behavior.
      When migrating to the sea, Arctic charr have regained a strong appetite and
      within 4-6weeks in the sea they may have doubled their body weight and increased
      their body fat stores several-fold, in anticipation of the resources needed for
      reproduction in the autumn and overwintering. All these processes are regulated
      independently of environmental changes; captive offspring of anadromous charr
      kept in freshwater displays seasonal changes in seawater tolerance and strong
      seasonal changes in food intake and growth even when they are continuously fed in
      excess and held at a constant water temperature in freshwater. A correct timing
      of these events is crucial for their survival in the Arctic and the Arctic charr
      seems to possess timing mechanisms that include endogenous, circannual
      oscillator(s) entrainable by photoperiod. The entrainment mechanism may be linked
      to diel melatonin rhythms, which in this species exactly mirror overground
      photoperiod, even during the winter residence in lakes with thick ice and snow.
      Little is known, however, about how photoperiod, melatonin and putative
      endogenous clock(s) interact in the generation of seasonal rhythms in fish, and
      downstream neuroendocrine mechanisms leading to physiological changes. The
      anadromous Arctic charr seems ideal as a model for studying such mechanisms. 

PMID- 24291061
TI  - Permanent draft genome of Rhodopirellula rubra SWK7.
AB  - The genome of Rhodopirellula rubra strain SWK7 was sequenced as a permanent draft
      to complement the full genome sequence of the type strain Rhodopirellula baltica
      SH1(T). This isolate is part of a larger study to infer the biogeography of
      Rhodopirellula species in European marine waters, as well as to amend the genus
      description of R. baltica. This genomics resource article is the fourth among a
      series of five publications reporting in a total of eight new permanent draft
      genomes of Rhodopirellula species. 

PMID- 24291062
TI  - The burden of influenza in England by age and clinical risk group: a statistical
      analysis to inform vaccine policy.
AB  - OBJECTIVES: To assess the burden of influenza by age and clinical status and use
      this to inform evaluations of the age and risk-based influenza vaccination policy
      in the United Kingdom. METHODS: Weekly laboratory reports for influenza and 7
      other respiratory pathogens were extracted from the national database and used in
      a regression model to estimate the proportion of acute respiratory illness
      outcomes attributable to each pathogen. RESULTS: Influenza accounted for ~10% of
      the attributed respiratory admissions and deaths in hospital. Healthy children
      under five had the highest influenza admission rate (1.9/1000). The presence of
      co-morbidities increased the admission rate by 5.7 fold for 5-14 year olds (from
      0.1 to 0.56/1000), the relative risk declining to 1.8 fold in 65+ year olds (from
      0.46 to 0.84/1000). The majority (72%) of influenza-attributable deaths in
      hospital occurred in 65+ year olds with co-morbidities. Mortality in children
      under 15 years was low with around 12 influenza-attributable deaths in hospital
      per year in England; the case fatality rate was substantially higher in risk than
      non-risk children. Infants under 6 months had the highest consultation and
      admission rates, around 70/1000 and 3/1000 respectively. CONCLUSIONS: Additional
      strategies are needed to reduce the remaining morbidity and mortality in the high
      risk and elderly populations, and to protect healthy children currently not
      offered the benefits of vaccination.

PMID- 24291063
TI  - Consequences of metal exposure on retinoid metabolism in vertebrates: a review.
AB  - What we generally refer to as 'vitamin A' is a group of naturally-occurring
      molecules structurally similar to retinol that are capable of exerting biological
      activity. These retinoids are essential to diverse physiological functions
      including vision, immune response, bone mineralization, reproduction, cell
      differentiation, and growth. As well, some retinoids have antioxidant properties.
      Independent studies published over the last few decades have revealed that many
      fish and wildlife populations living in highly polluted environments have altered
      retinoid status possibly associated with retinoid metabolic or homeostatic
      mechanisms. Substantial evidence links organic contaminant exposure with changes
      in retinoid status in animal populations, but only a few detailed studies have
      been published implicating inorganic contaminants such as metals. This mini
      review selectively deals with field and laboratory studies reporting associations
      between environmental contaminants, especially trace metals, and alterations in
      retinoid status. Both essential and non-essential trace metals have been reported
      to affect retinoid status. This review focuses on metabolic imbalances of
      retinoids in relation to metal contamination and illustrates possible modes of
      action. The role of retinoids as antioxidants and their potential as biomarkers
      of metal contamination are discussed. 

PMID- 24291064
TI  - Neuropeptide Y regulates the leptin receptors in rat hypothalamic and pituitary
      explant cultures.
AB  - The aim of this work was to investigate whether the expression of leptin
      receptors (OBR) in the hypothalamic-pituitary (HP) axis is regulated by the
      orexigenic neuropeptide Y (NPY) during ovulation. To this end, we performed in
      vitro assays, using cultures of both hypothalamic and anterior pituitary explants
      from immature rats primed with gonadotropins to induce ovulation. In hypothalamic
      explants, protein expression of both the long and short OBR isoforms was
      increased by the presence of NPY at 100-500 ng/ml and at 300-500 ng/ml,
      respectively. Similarly, in pituitary explants, protein expression of the long
      isoform was increased between 30 and 300 ng/ml while that of the short isoform
      was increased only at 300 ng/ml. When both tissues were incubated with NPY and
      BIBP3226, a specific antagonist of the NPY Y1 receptor subtype, the NPY-induced
      protein expression was totally reversed by the antagonist at almost every
      concentration assayed. However, this antagonist was not always capable of
      blocking the increase caused by the presence of NPY at transcript level. In
      conclusion, our results indicate that NPY is able to regulate the expression of
      both the long and the short isoforms of OBR in the HP axis, at least in part,
      through the NPY Y1 receptor. These results reinforce the fact that NPY and its
      NPY Y1 receptor play a critical role in reproduction by modulating leptin
      sensitivity.

PMID- 24291065
TI  - NOS2A promoter (CCTTT)n association with TB lacks independent functional
      correlation amongst Indians.
AB  - A penta-nucleotide microsatellite marker (CCTTT)n, in NOS2A promoter region has
      been associated with a variety of infectious diseases, including Tuberculosis.
      Most of these studies, however, are limited in justifying the association to
      tuberculosis through independent functional assays. The present study on 915
      individuals from three geographically distinct populations of India focused on
      the association and function simultaneously. PCR-Polyacrylamide Gel
      Electrophoresis and direct sequencing revealed the association of (CCTTT)10
      allele with protection against Tuberculosis in all the three populations (i)
      independently: Odisha [p = 0.0025, pc = 0.025, OR (95%CI) = 0.5 (0.39-0.82)],
      Chhattisgarh-tribe [p = 0.0001, pc = 0.001, OR (95%CI) = 0.3 (0.19-0.60)] and
      Sahariya tribe [p = 0.02, pc = 0.2, OR (95%CI) = 0.27 (0.08-0.84)]; and (ii)
      together: [p < 0.0001, pc < 0.001, OR (95%CI) = 0.47 (0.35-0.63)]. In-vitro dual
      luciferase reporter assay revealed that (CCTTT)n microsatellite affected the
      expression of the reporter gene without enhancing the promoter strength in repeat
      size specific manner. Thus the genetic association observed did not correlate
      exactly with the expression pattern and probably depended on flanking promoter
      SNPs (rs2779249 & rs140293907) not in strong LD with the microsatellite, and this
      effect needs future confirmation. 

PMID- 24291066
TI  - Damaging role of neutrophilic infiltration in a mouse model of progressive
      tuberculosis.
AB  - Tuberculosis was studied using an experimental model based on the C3HeB/FeJ mouse
      strain, which mimics the liquefaction of caseous necrosis occurring during active
      disease in immunocompetent adults. Mice were intravenously infected with 2 *
      10(4) Colony Forming Units of Mycobacterium tuberculosis and their
      histopathology, immune response, bacillary load, and survival were evaluated. The
      effects of the administration of drugs with anti-inflammatory activity were
      examined, and the C3H/HeN mouse strain was also included for comparative
      purposes. Massive intra-alveolar neutrophilic infiltration led to rapid granuloma
      growth and coalescence of lesions into superlesions. A central necrotic area
      appeared showing progressive cellular destruction, the alveoli cell walls being
      initially conserved (caseous necrosis) but finally destroyed (liquefactive
      necrosis). Increasing levels of pro-inflammatory mediators were detected in
      lungs. C3HeB/FeJ treated with anti-inflammatory drugs and C3H/HeN animals
      presented lower levels of pro-inflammatory mediators such as TNF-alpha, IL-17, IL
      6 and CXCL5, a lower bacillary load, better histopathology, and increased
      survival compared with untreated C3HeB/FeJ. The observation of massive
      neutrophilic infiltration suggests that inflammation may be a key factor in
      progression towards active tuberculosis. On the basis of our findings, we
      consider that the C3HeB/FeJ mouse model would be useful for evaluating new
      therapeutic strategies against human tuberculosis. 

PMID- 24291067
TI  - Are macrophages, myeloid derived suppressor cells and neutrophils mediators of
      local suppression in healthy and cancerous tissues in aging hosts?
AB  - Most cancers emerge in elderly and immune-comprised hosts implying an important
      role for cancer immune surveillance. Here, we focus on the role of tissue
      associated innate immune cells including antigen presenting cells (i.e. dendritic
      cells and macrophages), myeloid derived suppressor cells and neutrophils in
      healthy and cancer-bearing elderly hosts. Most cancers, including the cancers
      that we are interested in, i.e. lung carcinomas and mesothelioma, emerge in aging
      populations at a time when naive T cell function is declining. CD8(+) cytotoxic T
      lymphocytes are critical anti-tumor effector cells, and their diminished function
      may contribute to cancer escape mechanisms in the elderly. Therefore, we compare
      the likely consequences of innate immune cell interactions with T cells in young
      versus elderly hosts. We examine data showing that elderly-derived innate cells
      are highly immunosuppressive and may provide a more tumorigenic milieu than their
      younger counterparts. Standard chemotherapy often only provides these patients a
      few extra months survival time. Recent evidence has shown that standard
      chemotherapy is not as effective in hosts devoid of T cells. Therefore, T cell
      dysfunction in the elderly may contribute to poor treatment outcomes. However,
      there is also evidence that T cell immunity can be rejuvenated via activated
      dendritic cells and/or macrophages. Combining 'rejuvenation' immunotherapy with
      standard chemotherapy may offer an improved outcome for elderly cancer patients.
      We explore this potential herein. 

PMID- 24291068
TI  - Immunosenenescence: role of cytomegalovirus.
AB  - "Immunosenescence" is a loosely descriptive designation for age-associated
      alterations to most measures of immunity, which can be seen in all mammals
      examined in any detail. Both innate and adaptive immunity are affected in a
      manner assumed to be deleterious, but often the clinical consequences of the
      assessed changes are unclear or not even investigated. The mechanisms accounting
      for these changes, and biomarkers of immunosenescence, are currently the subject
      of intensive research. Cross-sectional studies have established hallmark age
      associated differences between adaptive immune factors in young and old people,
      particularly a lower number and percentage of naive T cells, especially CD8+ T
      cells, and accumulations of late-differentiated CD8+ T cells. The latter but not
      the former is strongly affected by infection with the persistent beta-herpesvirus
      HHV5 (cytomegalovirus, CMV). Only limited longitudinal studies have so far
      investigated whether these differences actually reflect age-associated changes at
      the individual level. The Swedish OCTO/NONA-Immune studies identified a set of
      immune parameters including infection with CMV which predicted survival in people
      over 85 at baseline. Moreover, the Leiden 85+ study showed that T cell-mediated
      pro-inflammatory specific for CMV antigens was enriched in very old survivors,
      suggesting the overarching necessity of maintaining effective immunosurveillance
      of this virus. Here, the disparate impact of CMV on "immunosenescence" and
      survival in human populations under different condition is reviewed. 

PMID- 24291069
TI  - Investigating the relationship between run-off-the-road crash frequency and
      traffic flow through different functional forms.
AB  - Crash prediction models play a major role in highway safety analysis. These
      models can be used for various purposes, such as predicting the number of road
      crashes or establishing relationships between these crashes and different
      covariates. However, the appropriate choice for the functional form of these
      models is generally not discussed in research literature on road safety. In case
      of run-off-the-road crashes, empirical evidence and logical considerations lead
      to conclusion that the relationship between expected frequency and traffic flow
      is not monotonously increasing. 

PMID- 24291070
TI  - A different perspective on conspicuity related motorcycle crashes.
AB  - The most common type of conflict in which a motorcyclist is injured or killed is
      a collision between a motorcycle and a car, often in priority situations. Many
      studies on motorcycle safety focus on the question why car drivers fail to give
      priority and on the poor conspicuity of motorcycles. The concept of 'looked-but
      failed-to-see' crashes is a recurring item. On the other hand, it is not entirely
      unexpected that motorcycles have many conflicts with cars; there simply are so
      many cars on the road. This paper tries to unravel whether - acknowledging the
      differences in exposure - car drivers indeed fail to yield for motorcycles more
      often than for other cars. For this purpose we compared the causes of crashes on
      intersections (e.g. failing to give priority, speeding, etc.) between different
      crash types (car-motorcycle or car-car). In addition, we compared the crash
      causes of dual drivers (i.e. car drivers who also have their motorcycle licence)
      with regular car drivers. Our crash analysis suggests that car drivers do not
      fail to give priority to motorcycles relatively more often than to another car
      when this car/motorcycle approaches from a perpendicular angle. There is only one
      priority situation where motorcycles seem to be at a disadvantage compared to
      cars. This is when a car makes a left turn, and fails to give priority to an
      oncoming motorcycle. This specific crash scenario occurs more often when the
      oncoming vehicle is a motorcycle than when it is a car. We did not find a
      significant difference between dual drivers and regular car drivers in how often
      they give priority to motorcycles compared to cars. 

PMID- 24291071
TI  - External validity of a generic safety climate scale for lone workers across
      different industries and companies.
AB  - PURPOSE: The goal of this study was to examine the external validity of a 12-item
      generic safety climate scale for lone workers in order to evaluate the
      appropriateness of generalized use of the scale in the measurement of safety
      climate across various lone work settings. External validity evidence was
      established by investigating the measurement equivalence (ME) across different
      industries and companies. METHOD: Confirmatory factor analysis (CFA)-based and
      item response theory (IRT)-based perspectives were adopted to examine the ME of
      the generic safety climate scale for lone workers across 11 companies from the
      trucking, electrical utility, and cable television industries. RESULTS: Fairly
      strong evidence of ME was observed for both organization- and group-level generic
      safety climate sub-scales. Although significant invariance was observed in the
      item intercepts across the different lone work settings, absolute model fit
      indices remained satisfactory in the most robust step of CFA-based ME testing.
      IRT-based ME testing identified only one differentially functioning item from the
      organization-level generic safety climate sub-scale, but its impact was minimal
      and strong ME was supported. IMPLICATIONS: The generic safety climate scale for
      lone workers reported good external validity and supported the presence of a
      common feature of safety climate among lone workers. The scale can be used as an
      effective safety evaluation tool in various lone work situations.

PMID- 24291073
TI  - Causes of accidents in terrain parks: an exploratory factor analysis of
      recreational freestylers' views.
AB  - OBJECTIVE: This study examines ski and snowboard terrain park users' views on
      aspects associated with accidents by identifying and assessing variables that may
      influence the occurrence of accidents and the resulting injuries. METHODS: The
      research was conducted in a major resort in the Spanish Pyrenees, using
      information gathered from freestyle skiers and snowboarders aged 6 or older. To
      identify interrelationships among variables and to group the variables belonging
      to unified concepts, an exploratory factor analysis was performed using varimax
      rotation. RESULTS: The results revealed 5 factors that grouped the measured
      variables that may influence the occurrence of accidents while freestyling in
      terrain parks. The park features, conditions of the activity, and the user's
      personal conditions were found to have the most substantial influence on the
      freestylers' perceptions. CONCLUSIONS: Variables identified as components of the
      main factors of accident risk in terrain parks should be incorporated into resort
      management communication and policies.

PMID- 24291074
TI  - From partial to full-face transplantation: total ablation and restoration, a
      change in the reconstructive paradigm.
AB  - The innovation of composite vascularized allotransplantation has provided plastic
      and reconstructive surgeons with the ultimate tool for those patients that
      present with facial deformities that cannot be reconstructed with classical or
      more traditional techniques. Transplanting normal tissues allows for a true
      restorative surgery. Initial experiences included the substitution of missing
      anatomy, whereas after the first world's full-face transplant performed in
      Barcelona in March 2010, a true ablative surgery with a total restoration proved
      to be effective. We review the world's experience and the performance of our
      restorative protocol to depict this change in the reconstructive paradigm of
      facial transplantation. Facial transplants should be performed after a careful
      analysis of the defect, with a comprehensive ablation plan following esthetic
      units with sacrifice of all required tissues with a focus of global restoration
      of anatomy, aesthetics and function, respecting normal functioning muscles.
      Nowadays, facial transplants following strict esthetic units should restore
      disfigurement extending to small central areas, whereas major defects may require
      a total ablation and restoration with full-face transplants. 

PMID- 24291075
TI  - Mechanical strength test for orodispersible and buccal films.
AB  - There are no test procedures, definitions and specifications available how to
      determine mechanical strength of orodispersible or buccal films. Aim of the study
      was to develop an appropriate and discriminating method to feature the evaluation
      of marketed and newly developed film products covering well-known and new
      approaches. The limits for mechanical strength were set starting from a puncture
      strength of 0.06 N/mm(2) according to the obtained results from marketed
      products. Furthermore, elongation to break of the marketed films (1.03-6.54%) and
      prepared film samples (4.51-33.17%) offered information on the film properties.
      The developed mechanical strength test method was suitable for all film types
      without the need of a pre-defined specimen. A mechanical strength threshold could
      be specified for future orodispersible film development.

PMID- 24291076
TI  - Aspirin degradation in surface-charged TEMPO-oxidized mesoporous crystalline
      nanocellulose.
AB  - TEMPO-mediated surface oxidation of mesoporous highly crystalline Cladophora
      cellulose was used to introduce negative surface charges onto cellulose
      nanofibrils without significantly altering other structural characteristics. This
      enabled the investigation of the influence of mesoporous nanocellulose surface
      charges on aspirin chemical stability to be conducted. The negative surface
      charges (carboxylate content 0.44+/-0.01 mmol/g) introduced on the mesoporous
      crystalline nanocellulose significantly accelerated aspirin degradation, compared
      to the starting material which had significantly less surface charge (0.06+/-0.01
      mmol/g). This effect followed from an increased aspirin amorphisation ability in
      mesopores of the oxidized nanocellulose. These results highlight the importance
      of surface charges in formulating nanocellulose for drug delivery.

PMID- 24291077
TI  - Probing influence of methodological variation on active loading of acetazolamide
      into nanoliposomes: biophysical, in vitro, ex vivo, in vivo and rheological
      investigation.
AB  - In the present work comparative evaluation of acetate and pH gradient techniques
      for effective drug loading in liposomes has been investigated. The acetazolamide
      (ACZ) loaded liposomes prepared by two methods were analyzed by vesicle size
      analysis, zeta potential, percent encapsulation efficiency, in vitro drug release
      studies and intraocular pressure lowering activity. ICH guidelines were followed
      for determining stability of the prepared liposomes. The superiority of acetate
      gradient method for active loading of acetazolamide has been established. The
      prepared acetate gradient positive liposomes showed extended hypotensive effect
      when compared to other liposomal formulations. Thus ACZ loaded liposomes prepared
      by acetate gradient technique may serve as promising ocular delivery system in
      the treatment of glaucoma. The current work emphasizes the fact that the
      techniques used for active drug loading into liposomes strongly influence the
      pharmaceutical performance of the final formulation. 

PMID- 24291078
TI  - Synthesis and characterization of a novel controlled release zinc
      oxide/gentamicin-chitosan composite with potential applications in wounds care.
AB  - Freshly prepared ZnO nanoparticles were incorporated into a chitosan solution in
      weight ratios ranging from 1:1 to 12:1. Starting from the ratio of 3:1 the
      chitosan solution was transformed into a gel with a high consistency, which
      incorporates 15mL water for only 0.1g solid substance. The powders obtained after
      drying the gel were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and thermal analysis (TG-DSC). The electronic (UV-vis),
      infrared (FTIR) and photoluminescence (PL) spectra were also recorded. ZnO
      particles were coated with gentamicin and incorporated into the chitosan matrix,
      to yield a ZnO/gentamicin-chitosan gel. The release rate of gentamicin was
      monitored photometrically. This ZnO/gentamicin-chitosan gel proved great
      antimicrobial properties, inhibiting Staphylococcus aureus and Pseudomonas
      aeruginosa growth in both planktonic and surface-attached conditions. The results
      indicate that the obtained composite can be used in cutaneous healing for
      developing improved wound dressings, which combine the antibacterial activity of
      all three components with the controlled release of the antibiotic. This wound
      dressing maintains a moist environment at the wound interface, providing a
      cooling sensation and soothing effect, while slowly releasing the antibiotic. The
      system is fully scalable to any other soluble drug, as the entire solution
      remains trapped in the ZnO-chitosan gel. 

PMID- 24291079
TI  - Effects of aging on structure and stability of TiO2 nanoparticle-containing oil
      in-water emulsions.
AB  - Formulations incorporating different cosmetic grade TiO2 nanoparticles were
      developed according to a self-produced protocol on the basis of typical sunscreen
      cream oil-in-water emulsions. Role of nanoparticles and, more specifically, the
      impact of two different lipophilic surface treatments on microstructure and
      stability of the formulations were assessed. Aging of formulations was performed
      under classical conditions at room temperature or under accelerated conditions at
      50  degrees C, with or without TiO2, and was characterized by several tools such
      as rheology, microscopy, and particle size measurements. Changes in emulsion
      stability and aggregation state of nanoparticles were followed over time.
      Destabilization phenomena were identified: under accelerated aging, the
      formulation without nanoparticles underwent a coalescence occurrence whereas the
      formulation incorporating nanoparticles was subjected to aggregation of the
      colloidal particles. Besides, TiO2 nanoparticles strongly affected the particle
      droplets interactions and thus modified the emulsion microstructure with a
      coating-dependent effect: destabilization mechanisms occur more rapidly with
      alumina (and) triethoxycaprylylsilane (coating 1) TiO2 nanoparticles as compared
      to alumina (and) isopropyl titanium triisostearate (and) triethoxycaprylylsilane
      crosspolymer (coating 2) nanoparticles.

PMID- 24291080
TI  - Public engagement workshop: how to improve medicines for older people?
AB  - Public engagement in medication management has become more and more important in
      promoting population health. A public engagement workshop attended by 78 members
      of the geriatric community, family carers as well as professionals from academic
      research, industry and regulatory agencies entitled 'How to improve medicines for
      older people?' took place on the 2nd July 2013 at the University College London
      (UCL) School of Pharmacy. The main aim of the event was to provide a dynamic
      environment for information exchange and to identify ways of improving current
      and future geriatric drug therapy. The day opened with presentations from UCL
      School of Pharmacy researchers on the use of medicines at home, formulations,
      administration devices and multi-component compliance aids (MCAs) whilst a
      representative from UCL Interaction Centre gave an insightful presentation on
      human errors and resilience strategies regarding medication use. These opening
      presentations encouraged participants to share their own experiences as well as
      initiating a lively debate. Following the plenary presentations, the workshop was
      divided into 8 groups for parallel discussion session. These opinion sharing
      sessions witnessed fruitful discussions between patients, carers and researchers.
      The day closed with a panel session of representatives from the European
      Medicines Agency (EMA), the Medicines and Healthcare products Regulatory Agency
      (MHRA), the Geriatric Medicines Society and Guy's and St. Thomas' NHS Foundation
      Trust (GSTT). Participants were encouraged to voice their questions, concerns and
      recommendations about medications. The main concern expressed by both patients
      and carers from the workshop were (but are not limited to) formulation changes,
      MCA accessibility difficulties, interactions of different medicines, carers'
      concerns with the administration of medicines and not having enough knowledge of
      services provided by community pharmacists i.e. medicines use reviews (MURs) or
      new medicine service (NMS). Overall, this workshop created a useful forum for
      members of the geriatric community, their carers as well as research and
      industrial professionals to have an input in the improvement and management of
      geriatric drug therapy and this event also provided an excellent opportunity for
      the researchers to share the latest research innovations with attendees. 

PMID- 24291072
TI  - Tracking progesterone receptor-mediated actions in breast cancer.
AB  - Ovarian steroid hormones contribute to breast cancer initiation and progression
      primarily through the actions of their nuclear transcription factors, the
      estrogen receptor alpha (ERalpha) and progesterone receptors (PRs). These
      receptors are important drivers of the luminal A and B subtypes of breast cancer,
      where estrogen-blocking drugs have been effective endocrine therapies for
      patients with these tumors. However, many patients do not respond, or become
      resistant to treatment. When endocrine therapies fail, the luminal subtypes of
      breast cancer are more difficult to treat because these subtypes are among the
      most heterogeneous in terms of mutation diversity and gene expression profiles.
      Recent evidence suggests that progestin and PR actions may be important drivers
      of luminal breast cancers. Clinical trial data has demonstrated that hormone
      replacement therapy with progestins drives invasive breast cancer and results in
      greater mortality. PR transcriptional activity is dependent upon cross-talk with
      growth factor signaling pathways that alter PR phosphorylation, acetylation, or
      SUMOylation as mechanisms for regulating PR target gene selection required for
      increased cell proliferation and survival. Site-specific PR phosphorylation is
      the primary driver of gene-selective PR transcriptional activity. However, PR
      phosphorylation and heightened transcriptional activity is coupled to rapid PR
      protein degradation; the range of active PR detected in tumors is likely to be
      dynamic. Thus, PR target gene signatures may provide a more accurate means of
      tracking PR's contribution to tumor progression rather than standard clinical
      protein-based (IHC) assays. Further development of antiprogestin therapies should
      be considered alongside antiestrogens and aromatase inhibitors. 

PMID- 24291081
TI  - On the correlation of output rate and aerodynamic characteristics in vibrating
      mesh-based aqueous aerosol delivery.
AB  - Aerosolization of aqueous formulations is of special interest for inhalative drug
      delivery, where an adequate nebulizer performance represents a prerequisite for
      improving pulmonary therapy. The present study investigated the interplay of
      output rate and aerodynamic characteristics of different excipient-based
      formulations and its impact on the atomization process by vibrating-mesh
      technology (i.e. eFlow((r))rapid). Output rate and aerodynamic characteristics
      were manipulated by both dynamic viscosity and conductivity of the applied
      formulation. Supplementation with sucrose and sodium chloride caused a decline
      (down to ~0.2 g/min) and elevation (up to ~1.0 g/min) of the nebulizer output
      rate, respectively. However, both excipients were capable of decreasing the
      aerodynamic diameter of produced aerosol droplets from >7.0 MUm to values of
      <=5.0 MUm. Thus, the correlation of output rate and aerodynamic characteristics
      resulted in linear fits of opposite slopes (R(2)>0.85). Finally, the overall
      number of delivered aerosol droplets per time was almost constant for sucrose
      (<=1*10(8) droplets/s), while for sodium chloride a concentration-dependent
      increase was observed (up to ~3*10(8) droplets/s). Overall, the current findings
      illustrated the influence of formulation parameters on the aerosolization process
      performed by vibrating-mesh technology. Moreover, concentration and charge
      distribution of aerosol populations supposedly modify the final characteristics
      of the delivered aerosols.

PMID- 24291082
TI  - Copper-driven avoidance and mortality in temperate and tropical tadpoles.
AB  - Amphibians have experienced an accentuated population decline in the whole world
      due to many factors, one of them being anthropogenic contamination. The present
      study aimed to assess the potential effect of copper, as a worldwide and
      reference contaminant, on the immediate decline of exposed population due to
      avoidance and mortality responses in tadpoles of three species of amphibians
      across climatic zones: a South American species, Leptodactylus latrans, a North
      American species, Lithobates catesbeianus, and a European species, Pelophylax
      perezi. A non-forced exposure system with a copper gradient along seven
      compartments through which organisms could freely move was used to assess the
      ability of tadpoles to detect and avoid copper contamination. All species were
      able to avoid copper at a concentration as low as 100 MUg L(-1). At the lowest
      (sublethal) concentrations (up to 200 MUg L(-1)) avoidance played an exclusive
      role for the population decline, whereas at the highest concentrations (> 450 MUg
      L(-1)) mortality was the response determining population decline. The median
      concentrations causing exposed population immediate decline were 93, 106 and 180
      MUg L(-1) for Le. latrans, Li. catesbeianus and P. perezi, respectively.
      Contaminants might, therefore, act as environmental disruptors both by generating
      low-quality habitats and by triggering avoidance of tadpoles, which could be an
      important response contributing to dispersion patterns, susceptibility to future
      stressors and decline of amphibian populations (together with mortality).

PMID- 24291083
TI  - NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to
      goldfish (Carassius auratus).
AB  - In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics
      approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in
      goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart,
      liver and kidney tissues of goldfish. NMR profiling combined with statistical
      methods such as orthogonal partial least squares discriminant analysis (OPLS-DA)
      and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was
      developed to discern metabolite changes occurring after one week LCT exposure in
      brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of
      many metabolites (e.g., leucine, isoleucine and valine in brain and kidney;
      lactate in brain, heart and kidney; alanine in brain and kidney; choline in
      brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in
      brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate
      in brain; cis-aconitate in brain, and etc.), and broke the balance of
      neurotransmitters and osmoregulators, evoked oxidative stress, disturbed
      metabolisms of energy and amino acids. The implication of glutamate-glutamine
      gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first
      time. Our findings demonstrated the applicability and potential of metabolomics
      approach for the elucidation of toxicological effects of pesticides and the
      underlying mechanisms, and the discovery of biomarkers for pesticide pollution in
      aquatic environment. 

PMID- 24291084
TI  - Study of genetic damage in the Japanese oyster induced by an environmentally
      relevant exposure to diuron: evidence of vertical transmission of DNA damage.
AB  - Pesticides represent a major proportion of the chemical pollutants detected in
      French coastal waters and hence a significant environmental risk with regards to
      marine organisms. Commercially-raised bivalves are particularly exposed to
      pollutants, among them pesticides, as shellfish farming zones are subject to
      considerable pressure from agricultural activities on the mainland. The aims of
      this study were to determine (1) the genotoxic effects of diuron exposure on
      oyster genitors and (2) the possible transmission of damaged DNA to offspring and
      its repercussions on oyster fitness. To investigate these points, oysters were
      exposed to concentrations of diuron close to those detected in the Marennes
      Oleron Basin (two 7-day exposure pulses at 0.4 and 0.6 MUg L(-1)) during the
      gametogenesis period. Genomic abnormalities were characterized using two
      complementary approaches. The Comet assay was applied for the measurement of
      early and reversible primary DNA damage, whereas flow cytometry was used to
      assess the clastogenic and aneugenic effect of diuron exposure. Polar Organic
      Chemical Integrative Samplers (POCIS) were used in exposed and assay tanks to
      confirm the waterborne concentration of diuron reached during the experiment. The
      results obtained by the Comet assay clearly showed a higher level of DNA strand
      breaks in both the hemocytes and spermatozoa of diuron-exposed genitors. The
      transmission of damaged genetic material to gamete cells could be responsible for
      the genetic damage measured in offspring. Indeed, flow cytometry analyses showed
      the presence of DNA breakage and a significant decrease in DNA content in spat
      from diuron-exposed genitors. The transmission of DNA damage to the offspring
      could be involved in the negative effects observed on offspring development
      (decrease in hatching rate, higher level of larval abnormalities, delay in
      metamorphosis) and growth. In this study, the vertical transmission of DNA damage
      was so highlighted by subjecting oyster genitors to short exposures to diuron at
      medium environmental concentrations. The analysis of POCIS showed that oysters
      were exposed to integrated concentrations as low as 0.2 and 0.3 MUg L(-1),
      emphasizing the relevance of the results obtained and the risk associated to
      chemical contamination for oyster recruitment and fitness.

PMID- 24291085
TI  - Acute effects of Anabaena spiroides extract and paraoxon-methyl on freshwater
      cladocerans from tropical and temperate regions: links between the ChE activity
      and survival and its implications for tropical ecotoxicological studies.
AB  - Cholinesterase (ChE) activity was measured in Pseudosida ramosa and Daphnia
      magna, which had previously been exposed to Anabaena spiroides extract or to
      paraoxon-methyl for 48 h. These activities were then related to survival at 48 h.
      For A. spiroides extract, the observed 48-h LC50 was 2.27 and 2.70 * 10(6)cells
      mL(-1), while for paraoxon-methyl it was 0.60 and 2.17 MUg L(-1), respectively,
      for P. ramosa and D. magna. Dose-response relationships were obtained for both P.
      ramosa and D. magna, when exposed to A. spiroides extract or paraoxon-methyl.
      Thus, when the tested concentrations of the toxicants increased, ChE activity and
      survival decreased. The ratio between 48-h IC50 for ChE and 48-h LC50 ranged from
      75% to 81% for P. ramosa and from 77% to 81% for D. magna. This indicated that
      the concentrations of both A. spiroides extract and paraoxon-methyl that cause
      50% mortality also inhibit ChE activity by 50%. Also, it was found that, for P.
      ramosa, a 50% inhibition of ChE activity was associated with a survival of 59.5%
      and 60.9%, respectively, for A. spiroides extract and paraoxon-methyl. However,
      for D. magna, at high levels of inhibition of ChE activity, almost no mortality
      was detected. In this specific case, 50% inhibition of the ChE activity was
      associated with 90.4 and 95.4% survival for A. spiroides extract and paraoxon
      methyl, respectively. In contrast, enzyme inhibition slightly above 60% had a
      strong detrimental effect on survival in D. magna. These different patterns found
      in the relationship between ChE inhibition and survival may be due to species
      specific differences in the affinities of both acetylcholinesterase and
      pseudocholinesterases, since the cladoceran ChE assays were performed with whole
      body homogenates. In conclusion, when using ChE as a biochemical biomarker in
      risk assessment of cyanobacterial neurotoxic blooms in tropical regions, it is
      strongly recommended that native species are used, since our results revealed
      that P. ramosa was more sensitive than D. magna for both assay endpoints and both
      toxicants. Furthermore, the relationship between ChE activity and survival had a
      species-specific response. Therefore, the use of the model species D. magna in
      acute toxicity tests and ChE assays in tropical regions may lead to errors in the
      estimation of risks to the local species.

PMID- 24291086
TI  - Transcriptional expression levels and biochemical markers of oxidative stress in
      Mytilus galloprovincialis exposed to nickel and heat stress.
AB  - The present study aims to evaluate transcriptional expression levels and
      biochemical markers of oxidative stress responses to nickel (Ni) exposure along
      with heat stress gradient in a mussel (Mytilus galloprovincialis). For this
      purpose, we investigated the response of oxidative stress markers,
      metallothionein accumulation and gene expression in digestive gland of mussels
      exposed to a sublethal concentration of Ni (2.5MUM) along with a temperature
      gradient (18 degrees C, 22 degrees C, and 26 degrees C) for 24h and 72h. Ni
      digestive gland uptake was evaluated after the exposure periods. Co-exposure to
      Ni and higher temperature (26 degrees C) for 72h significantly decreased the
      antioxidant enzyme activities termed as catalase (CAT), superoxide dismutase
      (SOD) and glutathione-S-transferase (GST) and caused a pronounced increase of
      lipofuscin and neutral lipid (NL) accumulation. Ni-uptake was different with
      respect to the exposure periods and temperatures in Ni-exposed mussels. Sod, cat,
      gst, mt-10 and mt20 gene expression levels showed a substantial increased pattern
      in animals exposed for one day to heat stress compared to the control condition
      (18 degrees C). The same pattern but with highest level was registered in animals
      co-exposed to Ni and temperatures within one day. Three days exposure to 18
      degrees C, 22 degrees C and 26 degrees C, resulted in a significant decrease in
      mRNA abundance of cat, gst and sod and a significant down-regulation of mts
      targets (22 degrees C and 26 degrees C). Our data provide new insights into the
      importance of the early protective response of oxidative stress related-gene
      expression and regulation in mussels challenging heat stress and sublethal Ni
      concentration. 

PMID- 24291088
TI  - The value of frozen cartilage tissues without cryoprotection for genetic
      conservation.
AB  - Animal tissues frozen without cryoprotection are thought to be inappropriate for
      use as a donor for somatic cell nuclear transfer (SCNT) studies. Cells in tissues
      that have been frozen without a cryoprotectant are commonly thought to be dead or
      to have lost genomic integrity. However, in this study we show that the frozen
      auricular cartilage tissues of anatolian buffalo contain a considerable number of
      viable healthy cells. The cells in auricular cartilage tissues are resistant to
      cryo-injury at -80 degrees C. Primary cell cultures were established from
      defrosted ear tissues which were frozen without cryoprotectant. The growth and
      functional characteristics of primary cell cultures are characterized according
      to cell growth curve, cell cycle analysis, karyotype and GAG synthesis. The
      results indicate that frozen cartilage tissues could be valuable materials for
      the conservation of species and SCNT technology. 

PMID- 24291087
TI  - Molecular characterization and expression analysis of the autophagic gene beclin
      1 from the purse red common carp (Cyprinus carpio) exposed to cadmium.
AB  - Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in
      autophagy, which has been linked to diverse biological processes including
      immunity, development, tumor suppression, lifespan extension, etc. However, the
      relevant study about Beclin 1 is rare in fish compared with mammals. In this
      study, we isolated Beclin 1 gene from the kidney tissue of common carp (Cyprinus
      carpio) using rapid amplification of cDNA ends (RACE). The deduced amino acid
      sequence of cloned Beclin 1 comprised 447 amino acids, which showed approximately
      80.7% identity and 88.9% similarity to human Beclin 1. It possessed a typical Bcl
      2 homology domain 3 (BH3) and an evolutionarily conserved domain (ECD).
      Phylogenetic analysis demonstrated that common carp Beclin 1 formed a clade with
      zebrafish Beclin 1. To explore the relationship between Beclin 1 and cadmium (Cd)
      induced injury, a Cd exposure experiment was conducted. The result showed that Cd
      content was significantly increased in a dose-dependent manner in kidney after Cd
      exposure. Swelling and vacuolation of renal tubular epithelial cells, and
      glomerular hyalinization were observed. Renal leukocyte infiltration was
      diffusely distributed in the interstitial tissue. Real-time quantitative RT-PCR
      analysis revealed that the mRNA transcript level of Beclin 1 was markedly up
      regulated in a dose-dependent and time-dependent manner after exposure to Cd.
      Similarly, Western blot analysis indicated that its protein level was
      significantly elevated in a dose-dependent manner after Cd treatment. All the
      results indicate that the common carp Beclin 1 gene may play a regulatory role
      against Cd toxicity. 

PMID- 24291089
TI  - Local auxin sources orient the apical-basal axis in Arabidopsis embryos.
AB  - Establishment of the embryonic axis foreshadows the main body axis of adults both
      in plants and in animals, but underlying mechanisms are considered distinct.
      Plants utilize directional, cell-to-cell transport of the growth hormone auxin to
      generate an asymmetric auxin response that specifies the embryonic apical-basal
      axis. The auxin flow directionality depends on the polarized subcellular
      localization of PIN-FORMED (PIN) auxin transporters. It remains unknown which
      mechanisms and spatial cues guide cell polarization and axis orientation in early
      embryos. Herein, we provide conceptually novel insights into the formation of
      embryonic axis in Arabidopsis by identifying a crucial role of localized
      tryptophan-dependent auxin biosynthesis. Local auxin production at the base of
      young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo
      are required for the apical auxin response maximum and the specification of
      apical embryonic structures. Later in embryogenesis, the precisely timed onset of
      localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin
      response maximum, and specification of the root pole. Thus, the tight
      spatiotemporal control of distinct local auxin sources provides a necessary, non
      cell-autonomous trigger for the coordinated cell polarization and subsequent
      apical-basal axis orientation during embryogenesis and, presumably, also for
      other polarization events during postembryonic plant life.

PMID- 24291090
TI  - Modeling framework for the establishment of the apical-basal embryonic axis in
      plants.
AB  - The apical-basal axis of the early plant embryo determines the body plan of the
      adult organism. To establish a polarized embryonic axis, plants evolved a unique
      mechanism that involves directional, cell-to-cell transport of the growth
      regulator auxin. Auxin transport relies on PIN auxin transporters, whose polar
      subcellular localization determines the flow directionality. PIN-mediated auxin
      transport mediates the spatial and temporal activity of the auxin response
      machinery that contributes to embryo patterning processes, including
      establishment of the apical (shoot) and basal (root) embryo poles. However,
      little is known of upstream mechanisms guiding the (re)polarization of auxin
      fluxes during embryogenesis. Here, we developed a model of plant embryogenesis
      that correctly generates emergent cell polarities and auxin-mediated sequential
      initiation of apical-basal axis of plant embryo. The model relies on two
      precisely localized auxin sources and a feedback between auxin and the polar,
      subcellular PIN transporter localization. Simulations reproduced PIN polarity and
      auxin distribution, as well as previously unknown polarization events during
      early embryogenesis. The spectrum of validated model predictions suggests that
      our model corresponds to a minimal mechanistic framework for initiation and
      orientation of the apical-basal axis to guide both embryonic and postembryonic
      plant development.

PMID- 24291091
TI  - Molecular data reveal complex hybridization and a cryptic species of neotropical
      wild cat.
AB  - Hybridization among animal species has recently become more recognized as an
      important phenomenon, especially in the context of recent radiations. Here we
      show that complex hybridization has led to contrasting patterns of genomic
      composition among closely related species of the Neotropical cat genus Leopardus.
      We show strong evidence of ancient hybridization and introgression between the
      pampas cat (L. colocolo) and northeastern populations of tigrina (L. tigrinus),
      leading to remarkable cytonuclear discordance in the latter. In contrast,
      southern tigrina populations show recent and continuing hybridization with
      Geoffroy's cat (L. geoffroyi), leading to extreme levels of interspecific
      admixture at their contact zone. Finally, we demonstrate that two seemingly
      continuous Brazilian tigrina populations show no evidence of ongoing gene flow
      between them, leading us to support their formal recognition as distinct species,
      namely L. tigrinus in the northeast and L. guttulus in the south.

PMID- 24291092
TI  - Spindle assembly checkpoint of oocytes depends on a kinetochore structure
      determined by cohesin in meiosis I.
AB  - Since the dissolution of sister chromatid cohesion by separase and cyclin B
      destruction is irreversible, it is essential to delay both until all chromosomes
      have bioriented on the mitotic spindle. Kinetochores that are not correctly
      attached to the spindle generate the mitotic checkpoint complex (MCC), which
      inhibits the anaphase-promoting complex/cyclosome (APC/C) and blocks anaphase
      onset. This process is known as the spindle assembly checkpoint (SAC). The SAC is
      especially important in meiosis I, where bivalents consisting of homologous
      chromosomes held together by chiasmata biorient. Since the first meiotic division
      is unaffected by rare achiasmatic chromosomes or misaligned bivalents, it is
      thought that several tensionless kinetochores are required to produce sufficient
      MCC for APC/C inhibition. Consistent with this, univalents lacking chiasmata
      elicit a SAC-mediated arrest in Mlh1(-/-) oocytes. In contrast, chromatids
      generated by TEV protease-induced cohesin cleavage in Rec8(TEV/TEV) oocytes
      merely delay APC/C activation. Since the arrest of Mlh1(-/-)Rec8(TEV/TEV) oocytes
      is alleviated by TEV protease, even when targeted to kinetochores, we conclude
      that their SAC depends on cohesin as well as dedicated kinetochore proteins. This
      has important implications for aging oocytes, where cohesin deterioration will
      induce sister kinetochore biorientation and compromise MCC production, leading to
      chromosome missegregation and aneuploid fetuses.

PMID- 24291093
TI  - Presynaptic inhibition of gamma lobe neurons is required for olfactory learning
      in Drosophila.
AB  - The loss of heterotrimeric G(o) signaling through the expression of pertussis
      toxin (PTX) within either the alpha/beta or gamma lobe mushroom body neurons of
      Drosophila results in the impaired aversive olfactory associative memory
      formation. Herein, we focus on the cellular effects of G(o) signaling in the
      gamma lobe mushroom body neurons during memory formation. Expression of PTX in
      the gamma lobes specifically inhibits G(o) activation, leading to poor olfactory
      learning and an increase in odor-elicited synaptic vesicle release. In the gamma
      lobe neurons, training decreases synaptic vesicle release elicited by the
      unpaired conditioned stimulus -, while leaving presynaptic activation by the
      paired conditioned stimulus + unchanged. PTX expression in gamma lobe neurons
      inhibits the generation of this differential synaptic activation by conditioned
      stimuli after negative reinforcement. Hyperpolarization of the gamma lobe neurons
      or the inhibition of presynaptic activity through the expression of dominant
      negative dynamin transgenes ameliorated the memory impairment caused by PTX,
      indicating that the disinhibition of these neurons by PTX was responsible for the
      poor memory formation. The role for gamma lobe inhibition, carried out by G(o)
      activation, indicates that an inhibitory circuit involving these neurons plays a
      positive role in memory acquisition. This newly uncovered requirement for
      inhibition of odor-elicited activity within the gamma lobes is consistent with
      these neurons serving as comparators during learning, perhaps as part of an odor
      salience modification mechanism.

PMID- 24291094
TI  - Coordination of translational control and protein homeostasis during severe heat
      stress.
AB  - BACKGROUND: Exposure of cells to severe heat stress causes not only misfolding
      and aggregation of proteins but also inhibition of translation and storage of
      mRNA in cytosolic heat stress granules (heat-SGs), limiting newly synthesized
      protein influx into overloaded proteome repair systems. How these two heat stress
      responses connect is unclear. RESULTS: Here, we show that both S. cerevisiae and
      D. melanogaster heat-SGs contain mRNA, translation machinery components
      (excluding ribosomes), and molecular chaperones and that heat-SGs coassemble with
      aggregates of misfolded, heat-labile proteins. Components in these mixed
      assemblies exhibit distinct molecular motilities reflecting differential
      trapping. We demonstrate that heat-SG disassembly and restoration of translation
      activity during heat stress recovery is intimately linked to disaggregation of
      damaged proteins present in the mixed assemblies and requires Hsp104 and Hsp70
      activity. CONCLUSIONS: Chaperone-driven protein disaggregation directly
      coordinates timing of translation reinitiation with protein folding capacity
      during cellular protein quality surveillance, enabling efficient protein
      homeostasis.

PMID- 24291095
TI  - Aurora B inhibits MCAK activity through a phosphoconformational switch that
      reduces microtubule association.
AB  - BACKGROUND: Proper spindle assembly and chromosome segregation rely on precise
      microtubule dynamics, which are governed in part by the kinesin-13 MCAK. MCAK
      microtubule depolymerization activity is inhibited by Aurora B-dependent
      phosphorylation, but the mechanism of this inhibition is not understood. RESULTS:
      Here, we develop the first Forster resonance energy transfer (FRET)-based
      biosensor for MCAK and show that MCAK in solution exists in a closed conformation
      mediated by an interaction between the C-terminal domain (CT) and the neck. Using
      fluorescence lifetime imaging (FLIM) we show that MCAK bound to microtubule ends
      is closed relative to MCAK associated with the microtubule lattice. Aurora B
      phosphorylation at S196 in the neck opens MCAK conformation and diminishes the
      interaction between the CT and the neck. Using FLIM and TIRF imaging, we find
      that changes in MCAK conformation are associated with a decrease in MCAK affinity
      for the microtubule. CONCLUSIONS: Unlike motile kinesins, which are open when
      doing work, the high-affinity binding state for microtubule-depolymerizing
      kinesins is in a closed conformation. Phosphorylation switches MCAK conformation,
      which inhibits its ability to interact with microtubules and reduces its
      microtubule depolymerization activity. This work shows that the conformational
      model proposed for regulating kinesin activity is not universal and that
      microtubule-depolymerizing kinesins utilize a distinct conformational mode to
      regulate affinity for the microtubule, thus controlling their catalytic
      efficiency. Furthermore, our work provides a mechanism by which the robust
      microtubule depolymerization activity of kinesin-13s can be rapidly modulated to
      control cellular microtubule dynamics.

PMID- 24291096
TI  - Ryanodine receptors as leak channels.
AB  - Ryanodine receptors are Ca(2+) release channels of internal stores. This review
      focuses on those situations and conditions that transform RyRs from a finely
      regulated ion channel to an unregulated Ca(2+) leak channel and the pathological
      consequences of this alteration. In skeletal muscle, mutations in either CaV1.1
      channel or RyR1 results in a leaky behavior of the latter. In heart cells, RyR2
      functions normally as a Ca(2+) leak channel during diastole within certain
      limits, the enhancement of this activity leads to arrhythmogenic situations that
      are tackled with different pharmacological strategies. In smooth muscle, RyRs are
      involved more in reducing excitability than in stimulating contraction so the
      leak activity of RyRs in the form of Ca(2+) sparks, locally activates Ca(2+)
      dependent potassium channels to reduce excitability. In neurons the enhanced
      activity of RyRs is associated with the development of different
      neurodegenerative disorders such as Alzheimer and Huntington diseases. It appears
      then that the activity of RyRs as leak channels can have both physiological and
      pathological consequences depending on the cell type and the metabolic condition.

PMID- 24291097
TI  - IMM-H004, a novel courmarin derivative, protects against oxygen-and glucose
      deprivation/restoration-induced apoptosis in PC12 cells.
AB  - 7-Hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a
      novel coumarin derivative synthesized in our laboratory. The purpose of the
      current study was to determine the neuroprotective effects of IMM-H004 on PC12
      cells and its potential mechanism of action. PC12 cells were subject to oxygen
      and glucose deprivation (OGD) followed by the restoration of oxygen and glucose
      (R), which mimics ischemia and reperfusion in vivo. Cell viability was determined
      by MTT assay. DNA fragmentation was analyzed by DNA ladder. ROS and mitochondrial
      membrane potential were measured by fluorescent microscope and quantified by
      Image-Pro Express 6.0 software. ATP was measured by luciferin-luciferase assay.
      The activation of signal-regulated molecules was assessed by the Western blot
      analysis. OH formation was determined using the Electron Spin Resonance (ESR)
      trapping technique in combination with 5, 5-dimethyl-1-pyrroline-N-oxide. OGD/R
      reduced cell viability and induced cell apoptosis, which were both dose
      dependently attenuated by IMM-H004. The accumulation of intracellular reactive
      oxygen species (ROS) and reduced mitochondrial membrane potential observed in
      PC12 cells treated with OGD/R, which switch on the mitochondrion-dependent
      apoptotic pathway, were reversed by IMM-H004. ATP production in OGD/R-treated
      PC12 cells was elevated by IMM-H004, which suggests that it restored the
      functions of the mitochondria. OGD/R-induced cytochrome c release from the
      mitochondria reduced the ratio of apoptotic proteins, Bcl-2/Bax, and induced
      caspase-3 activation and DNA fragmentation. These changes were significantly
      inhibited by IMM-H004. IMM-H004 also significantly inhibited OH formation,
      determined by electron spin resonance, which indicates that it is a potent free
      radical scavenger. This study has demonstrated that IMM-H004 protects PC12 cells
      against OGD/R-induced apoptosis, at least in part, by scavenging excessive ROS
      and inhibiting the mitochondrion-dependent apoptotic pathway. 

PMID- 24291098
TI  - FK506-binding protein 1b/12.6: a key to aging-related hippocampal Ca2+
      dysregulation?
AB  - It has been recognized for some time that the Ca(2+)-dependent slow
      afterhyperpolarization (sAHP) is larger in hippocampal neurons of aged compared
      with young animals. In addition, extensive studies since have shown that other
      Ca(2+)-mediated electrophysiological responses are increased in hippocampus with
      aging, including Ca(2+) transients, L-type voltage-gated Ca(2+) channel activity,
      Ca(2+) spike duration and action potential accommodation. Elevated Ca(2+)-induced
      Ca(2+) release from ryanodine receptors (RyRs) appears to drive amplification of
      the Ca(2+) responses. Components of this Ca(2+) dysregulation phenotype correlate
      with deficits in cognitive function and plasticity, indicating they may play
      critical roles in aging-related impairment of brain function. However, the
      molecular mechanisms underlying aging-related Ca(2+) dysregulation are not well
      understood. FK506-binding proteins 1a and 1b (FKBP1a/1b, also known as
      FKBP12/12.6) are immunophilin proteins that bind the immunosuppressant drugs
      FK506 and rapamycin. In muscle cells, FKBP1a/1b also bind RyRs and inhibits
      Ca(2+)-induced Ca(2+) release, but it is not clear whether FKBPs act similarly in
      brain cells. Recently, we found that selectively disrupting hippocampal FKBP1b
      function in young rats, either by microinjecting adeno-associated viral vectors
      expressing siRNA, or by treatment with rapamycin, increases the sAHP and
      recapitulates much of the hippocampal Ca(2+) dysregulation phenotype. Moreover,
      in microarray studies, we found FKBP1b gene expression was downregulated in
      hippocampus of aging rats and early-stage Alzheimer's disease subjects. These
      results suggest the novel hypothesis that declining FKBP function is a key factor
      in aging-related Ca(2+) dysregulation in the brain and point to potential new
      therapeutic targets for counteracting unhealthy brain aging. 

PMID- 24291100
TI  - Targeting different angiogenic pathways with combination of curcumin, leflunomide
      and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in
      mice.
AB  - No effective chemopreventive agent has been approved against hepatocellular
      carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors,
      blocking angiogenesis represents an intriguing approach to HCC chemoprevention.
      The aim of the current study was to examine the combined effect of the anti
      angiogenic agents: leflunomide; a disease modifying antirheumatic drug,
      perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the
      active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice.
      Eight weeks following DEN administration, there was a significant rise in
      immunohistochemical staining of CD31-positive endothelial cells and consequently
      hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was
      associated with elevation in hepatic vascular endothelial growth factor (VEGF)
      level as compared to normal controls (P<0.05, 3842+/-72pg/ml and 2520.8+/
      97pg/ml, respectively). Similarly, increased hepatic expression of hypoxia
      inducible growth factor-1alpha (HIF-1alpha) was observed in 100% of the DEN
      treated animals compared to 0% in their normal counterparts. Treatment with
      leflunomide, perindopril or curcumin alone abrogated the DEN-induced increased
      MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF
      1alpha hepatic expression. Combination of these agents showed further inhibitory
      action on neovascularization and synergistic attenuation of hepatic VEGF
      (1954.27+/-115pg/ml) when compared to each single agent. Histopathological
      examination revealed a more beneficial chemopreventive activity in the
      combination group compared to each monotherapy. In conclusion, the combination
      treatment of leflunomide, perindopril and curcumin targeting different angiogenic
      pathways, resulted in synergistic inhibition of angiogenesis and consequently
      more effective chemoprevention of HCC. 

PMID- 24291099
TI  - Intracellular calcium channels in protozoa.
AB  - Ca(2+)-signaling pathways and intracellular Ca(2+) channels are present in
      protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and
      other intracellular channels predates the divergence of animals and fungi as
      evidenced by their presence in the choanoflagellate Monosiga brevicollis, the
      closest known relative to metazoans. The first protozoan IP3R cloned, from the
      ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R.
      This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in six
      subfamilies suggesting the evolutionary adaptation to local requirements for an
      expanding diversification of vesicle trafficking. IP3Rs have also been
      functionally characterized in trypanosomatids, where they are essential for
      growth, differentiation, and establishment of infection. The presence of the
      mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that
      mitochondrial regulation of Ca(2+) signaling is also an early appearance in
      evolution, and contributed to the discovery of the molecular nature of this
      channel in mammalian cells. There is only sequence evidence for the occurrence of
      two-pore channels (TPCs), transient receptor potential Ca(2+) channels (TRPCs)
      and intracellular mechanosensitive Ca(2+)-channels in Paramecium and in parasitic
      protozoa. 

PMID- 24291101
TI  - Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced
      constipation and visceral pain.
AB  - Constipation is a major gastrointestinal motility disorder with clinical need for
      effective drugs. We previously reported that transient receptor potential ankyrin
      1 (TRPA1) is highly expressed in enterochromaffin (EC) cells, which are 5
      hydroxytryptamine (5-HT)-releasing cells, and might therefore be a novel target
      for constipation. Here, we examined the effects of ASP7663, a novel and selective
      TRPA1 agonist, in constipation models as well as an abdominal pain model. ASP7663
      activated human, rat, and mouse TRPA1 and released 5-HT from QGP-1 cells, and
      oral but not intravenous administration of ASP7663 significantly improved the
      loperamide-induced delay in colonic transit in mice. While pretreatment with the
      TRPA1 antagonist HC-030031 and vagotomy both inhibited the ameliorating effect of
      oral ASP7663 on the colonic transit, both orally and intravenously administered
      ASP7663 significantly inhibited colorectal distension (CRD)-induced abdominal
      pain response in rats. Taken together, these results demonstrate that ASP7663
      exerts both anti-constipation and anti-abdominal pain actions, the former is
      likely triggered from the mucosal side of the gut wall via activation of vagus
      nerves while the latter is assumed to be provoked through systemic blood flow. We
      conclude that ASP7663 can be an effective anti-constipation drug with abdominal
      analgesic effect. 

PMID- 24291103
TI  - Calcium signalling and calcium channels: evolution and general principles.
AB  - Calcium as a divalent cation was selected early in evolution as a signaling
      molecule to be used by both prokaryotes and eukaryotes. Its low cytosolic
      concentration likely reflects the initial concentration of this ion in the
      primordial soup/ocean as unicellular organisms were formed. As the concentration
      of calcium in the ocean subsequently increased, so did the diversity of
      homeostatic molecules handling calcium. This includes the plasma membrane
      channels that allowed the calcium entry, as well as extrusion mechanisms, i.e.,
      exchangers and pumps. Further diversification occurred with the evolution of
      intracellular organelles, in particular the endoplasmic reticulum and
      mitochondria, which also contain channels, exchanger(s) and pumps to handle the
      homeostasis of calcium ions. Calcium signalling system, based around coordinated
      interactions of the above molecular entities, can be activated by the opening of
      voltage-gated channels, neurotransmitters, second messengers and/or mechanical
      stimulation, and as such is all-pervading pathway in physiology and
      pathophysiology of organisms. 

PMID- 24291102
TI  - Roles of subunit phosphorylation in regulating glutamate receptor function.
AB  - Protein phosphorylation is an important mechanism for regulating ionotropic
      glutamate receptors (iGluRs). Early studies have established that major iGluR
      subtypes, including alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) receptors and N-methyl-d-aspartate (NMDA) receptors, are subject to
      phosphorylation. Multiple serine, threonine, and tyrosine residues predominantly
      within the C-terminal regions of AMPA receptor and NMDA receptor subunits have
      been identified as sensitive phosphorylation sites. These distinct sites undergo
      either constitutive phosphorylation or activity-dependent phosphorylation induced
      by changing cellular and synaptic inputs. An increasing number of synapse
      enriched protein kinases have been found to phosphorylate iGluRs The common
      kinases include protein kinase A, protein kinase C, Ca(2+)/calmodulin-dependent
      protein kinase II, Src/Fyn non-receptor tyrosine kinases, and cyclin dependent
      kinase-5. Regulated phosphorylation plays a well-documented role in modulating
      the biochemical, biophysical, and functional properties of the receptor. In the
      future, identifying the precise mechanisms how phosphorylation regulates iGluR
      activities and finding the link between iGluR phosphorylation and the
      pathogenesis of various brain diseases, including psychiatric and
      neurodegenerative diseases, chronic pain, stroke, Alzheimer's disease and
      substance addiction, will be hot topics and could contribute to the development
      of novel pharmacotherapies, by targeting the defined phosphorylation process, for
      suppressing iGluR-related disorders. 

PMID- 24291104
TI  - Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor
      against Vismodegib-resistant Smoothened mutant.
AB  - Hedgehog signaling is a driving force in medulloblastoma and basal cell carcinoma
      (BCC), making it an attractive therapeutic target. Vismodegib recently received
      FDA approval for the treatment of inoperable BCC, but a drug-resistant Smoothened
      (Smo) mutant (D473H) was identified in a clinical study. TAK-441 is a pyrrolo[3,2
      c]pyridine-4-one derivative that potently inhibits Hh signal transduction and is
      currently under investigation in clinical trials. We demonstrated that TAK-441
      inhibits reporter activity in D473H-transfected cells with an IC50 of 79nM, while
      Vismodegib showed an IC50=7100nM. In order to investigate the mode of inhibition,
      we evaluated the Smo inhibitors with three different binding assays, such as
      [(3)H]-TAK-441 membrane binding assay, affinity selection-MS detection assay, and
      bodipy-cylopamine whole cell assay. In three different assays, Vismodegib and
      cyclopamine showed lower affinity for the D473H mutant in comparison with wild
      type Smo. On the other hand, TAK-441 showed almost equal binding affinity for the
      D473H mutant compared with wild-type Smo in the binding assays, although TAK-441
      binds to the same binding site as two other well-known inhibitors. These in vitro
      findings suggest that TAK-441 has the potential for clinical use in cancers that
      are dependent on Hedgehog signaling, including wild-type tumors and Vismodegib
      resistant D473H mutants. 

PMID- 24291105
TI  - Calcium permeability of ligand-gated Ca2+ channels.
AB  - Many of cation-permeable ionotropic receptors to various neurotransmitters, such
      as glutamate, acetylcholine and ATP, are permeable to Ca(2+) ions. For some of
      them, in particular NMDA, nicotinic Ach and P2X receptors, permeability to Ca(2+)
      is higher than permeability to monovalent cations. Such receptors can be viewed
      as ligand-gated Ca(2+)-channels (LGCCs). This review provides an overview of past
      works on structure LGCCs, including structural motifs responsible for their
      interaction with Ca(2+) ions, and functional implications of their Ca(2+)
      permeability. The NMDA, P2X and nicotinic Ach receptors are abundantly expressed
      in the central nervous system. They are present at the nerve terminals,
      postsynaptic, extrasynaptic and glial membrane and therefore can contribute to
      synaptic function at different levels. Their heteromeric structure leads to wide
      variety of LGCC subtypes and great diversity of their functional properties. The
      influx of Ca(2+) provided by LGCCs can activate a plethora of secondary messenger
      cascades, which can modulate activity, trafficking and lateral mobility of LGCCs
      and thereby are entangled with their physiological function. In the discussion of
      the physiological importance of LGCCs we are focusing on emerging evidence on
      their role in control of synaptic transmission, plasticity and glia-neuron
      interaction. 

PMID- 24291106
TI  - Calcium channels, external calcium concentration and cell proliferation.
AB  - Evidence for a role for calcium channel proteins in cell proliferation is
      numerous suggesting that calcium influx is essential in this physiological
      process. Several studies in the past thirty years have demonstrated that calcium
      channel expression levels are determinant in cell proliferation. Voltage-gated,
      store-operated, second messengers and receptor-operated calcium channels have
      been associated to cell proliferation. However, the relationship between calcium
      influx and cell proliferation can be uncoupled in transformed and cancer cells,
      resulting in an external calcium-independent proliferation. Thus, protein
      expression could be more important than channel function to trigger cell
      proliferation suggesting that additional channel functions may be responsible to
      reconcile calcium channel expression and cell proliferation. When needed,
      external calcium concentration is obviously important for calcium channel
      function but it also regulates calcium sensing receptor (CaSR) activity. CaSR can
      up- or down-regulate cell proliferation depending on physiological conditions.
      CaSR sensitivity to external calcium is within the 0.5 to 5 mM range and
      therefore, the role of these receptors in cell proliferation must be taken into
      account. We therefore suggest here that cell proliferation rates could depend on
      the relative balance between calcium influx and CaSR activation.

PMID- 24291107
TI  - Calcium channels and their blockers in intraocular pressure and glaucoma.
AB  - Several factors besides high intraocular pressure assumed to be associated with
      the development and progression of glaucoma, and calcium channel blockers (CCBs)
      have been an anticipated option for glaucoma treatment by improving ocular
      perfusion and/or exerting neuroprotective effects on retinal ganglion cells with
      safety established in wide and long-term usage. Decrease in IOP has been reported
      after topical application of CCBs, however, the effect is much smaller and almost
      negligible after systemic application. Various CCBs have been reported to
      increase posterior ocular blood flow in vivo and to exert direct neuroprotection
      in neurons in vitro. Distribution of the drug at a pharmacologically active
      concentration in the posterior ocular tissues across the blood-brain barrier or
      blood-retina barrier, especially in the optic nerve head and retina where the
      ganglion cells mainly suffer from glaucomatous damage, is essential for clinical
      treatment of glaucoma. Improved visual functions such as sensitivity in the
      visual field test have been reported after administration of CCBs, but evidences
      from the randomized studies have been limited and effects of CCBs on blood flow
      and direct neuroprotection are hardly distinguished from each other. 

PMID- 24291108
TI  - How ORAI and TRP channels interfere with each other: interaction models and
      examples from the immune system and the skin.
AB  - Four types of Ca(2+) selective ion channels are known, ten voltage gated Ca(2+)
      (CaV) channels, four CatSper channels, three store operated CRAC channels (ORAI
      channels) and at least two members of the TRPV subfamily (TRPV5, TRPV6). Some of
      the other TRP channels also show some Ca(2+) selectivity like certain splice
      variants of TRPM3. In addition to Ca(2+) selective channels, various cation
      channels play an important role for Ca(2+) entry and furthermore, they may also
      regulate Ca(2+) entry through other channels by modulating the membrane potential
      or other means as outlined in this review. Of the different types of cation
      channels, TRP channels form one of the most prominent families of non-selective
      cation channels with functional relevance in electrically non-excitable and
      electrically excitable cell types. Among these, the seven channels of the TRPC
      subfamily are rather non-selective with very modest Ca(2+) selectivity, whereas
      in the other subfamilies, cation selectivity ranges from monovalent selectivity
      (i.e. TRPM4, TRPM5) to divalent selectivity (i.e. TRPM6, TRPM7) or Ca(2+)
      selectivity (i.e. TRPV5, TRPV6). Rather than discussing the heavily reviewed
      individual functions of ORAI or TRP channels, we summarize data and present
      models how TRP and ORAI may functionally interact to guide cellular functions. We
      focus on T lymphocytes representing a more ORAI-dominated tissue and skin as
      model system in which both ORAI and TRP channel have been reported to control
      relevant functions. We present several interaction models how ORAI and TRP may
      interfere with each other's function. 

PMID- 24291109
TI  - Physico-chemical characterization in solution and in the solid state of
      clonazepam complexes with native and chemically-modified cyclodextrins.
AB  - Clonazepam (CLZ) is a benzodiazepine derivative, whose bioavailability, limited
      by its very poor water-solubility, could be improved by cyclodextrin
      complexation. However, the choice of the most proper cyclodextrin to use to fully
      exploit its potential favourable effects on the drug, is a critical step.
      Therefore, in the present work, the performance of some amorphous cyclodextrin
      (CD) derivatives in terms of complexing, solubilizing and amorphizing power
      towards CLZ was carefully evaluated and compared with that of natural CDs. The
      role of CD cavity size, amorphous or crystalline nature, and presence and type of
      substituents on its ability in producing effective interactions with the drug has
      been investigated. Equimolar CLZ-CD solid systems were obtained by blending,
      kneading, co-grinding and coevaporation. Drug-CD interactions were investigated
      by phase-solubility analysis, differential scanning calorimetry and X-ray powder
      diffractometry. Among the natural CDs, beta-CD showed the highest complexing
      ability, suggesting that its cavity size is the most proper to host the drug
      molecule. The presence of substituents had a negative effect on the performance
      of alpha-CD and gamma-CD, while it improved the complexing and solubilizing power
      of beta-CD, and the methylated derivative was more effective than the
      hydroxypropylated one. Solid-state studies revealed that amorphous CDs had
      highest amorphizing power than the corresponding natural crystalline ones, and
      methylated-beta-CD (Me-beta-CD) was the best carrier. As for the preparation
      method, co-grinding was the most powerful in promoting the formation of
      efficacious drug-CD solid-state interactions. Dissolution rate studies confirmed
      Me-beta-CD as the best partner for CLZ and co-grinding as the best method for
      maximizing the drug dissolution properties. Therefore, co-ground products with Me
      beta-CD could be selected as the best system for future development of CLZ
      formulations with improved therapeutic efficacy. 

PMID- 24291110
TI  - Pharmacokinetic study of cinnamaldehyde in rats by GC-MS after oral and
      intravenous administration.
AB  - A selective and sensitive method utilizing gas chromatography-mass spectrometry
      was developed for simultaneous determination of cinnamaldehyde, cinnamyl alcohol,
      and methyl cinnamate in rat plasma. Cinnamaldehyde and cinnamyl alcohol can inter
      convert to one another in rats, thus simultaneous quantifying both analytes
      provided a reliable and accurate method of assessment. Three qualifying ions (131
      m/z, 105 m/z and 92 m/z) were chosen for simultaneous quantification of
      cinnamaldehyde and its metabolites. In this study, the calibration curves
      demonstrated a good linearity and reproducibility over the range of 20-2000ng/ml
      (r(2)>=0.999) for all analytes. Furthermore, the sensitivity of gas
      chromatography-mass spectrometry revealed sufficient lower limit of quantitation
      and detection of 20ng/ml and 5ng/ml, respectively, in the pharmacokinetic
      analysis. The intra- and inter-day precision variations were less than 10.4% and
      12.2%, respectively, whilst accuracy values ranged from -8.6% to 14.8%. All
      analytes were stable in plasma and in processed samples at room temperature for
      24h with no significant degradation after three freeze/thaw cycles. A small
      amount of the administered cinnamaldehyde had long half-life of 6.7+/-1.5h. In
      this study, gas chromatography-mass spectrometry was demonstrated to be a
      powerful tool for the pharmacokinetic studies of rats after intravenous and oral
      administration of cinnamaldehyde. 

PMID- 24291111
TI  - Development and validation of a highly sensitive LC-MS/MS method for
      quantification of IC87114 in mice plasma, bronchoalveolar lavage and lung
      samples: Application to pharmacokinetic study.
AB  - IC87114 is a selective PI3Kdelta inhibitor. A simple, sensitive and reliable LC
      MS/MS method with rapid sample preparation was developed and validated for the
      determination of IC87114 in mouse plasma, bronchoalveolar lavage, and lung.
      Chromatographic separation was achieved using an Agilent Zorbax Eclipse XDB-C18
      column (150mm*2.1mm internal diameter, 3.5MUm particle size). Mass spectrometric
      detection was conducted by electrospray ionization in positive ion multiple
      reaction monitoring modes. The calibration curve was linear over a concentration
      range of 0.01-1000ng/mL for plasma/BAL and 0.1-250ng/mL for lung tissue.
      Recoveries were as high as 97.29%, 102.81% and 89.70% for plasma, BAL fluid and
      lung sample, respectively. The lower limit of quantification was 0.01ng/mL. Intra
      day and inter-day accuracy and precision were within the acceptable limits of +/
      15% at all concentrations. Finally, the method was successfully used in a
      pharmacokinetic study that measured IC87114 in mouse plasma, BAL fluid and lung
      tissue after administration of a single 1mg/kg intratracheal dose of IC87114. The
      percentage change for incurred sample reanalysis (ISR) was within +/-15.0% and
      met the acceptance criteria for ISR. 

PMID- 24291112
TI  - Simultaneous analysis of antibiotics in biological samples by ultra high
      performance liquid chromatography-tandem mass spectrometry.
AB  - A rapid and reliable multiclass method was developed for the simultaneous
      analysis of 21 antibiotics (beta-lactams, aminoglycosides, penicillins,
      cephalosporins, carbapenems or quinolones) in urine, serum, cerebrospinal fluid
      (CSF) and bronchial aspirations by ultra-high performance liquid chromatography
      coupled to tandem mass spectrometry (UHPLC-MS/MS). Prior to chromatographic
      determination, the analytes were extracted from human biological fluids by simple
      sample treatments, which imply dilution, liquefaction, or protein precipitation.
      Several chromatographic conditions were optimized in order to obtain a fast
      separation (<6min for each chromatographic run). MS/MS conditions were evaluated
      in order to increase selectivity and sensitivity and all compounds were detected
      in electrospray (ESI) positive ion mode, except clavulanic acid and sulbactam,
      which were monitored in negative ion mode. The developed method was validated in
      terms of linearity, selectivity, limits of detection (LODs) and quantification
      (LOQs), trueness, repeatability and interday precision. The LOQs ranged from 0.01
      to 1.00mg/L for urine, serum and CSF. In case of bronchial aspirations, the LOQs
      were between 0.02 and 0.67mg/kg. In all matrices the recovery results were in the
      range 70-120% and interday precision was lower than 25%. Finally, the optimized
      method was applied to the analysis of biological samples from 10 patients in the
      intensive care unit (ICU) of a hospital located in Almeria (Spain). Several
      antibiotics (e.g., amoxicillin, tobramycin, levofloxacin, or linezolid) were
      found in the studied samples, observing that the highest concentrations were
      obtained in urine samples. 

PMID- 24291113
TI  - Novel insight into the natural history of short QT syndrome.
AB  - OBJECTIVES: This study intends to gain further insights into the natural history,
      the yield of familial and genetic screening, and the arrhythmogenic mechanisms in
      the largest cohort of short QT syndrome (SQTS) patients described so far.
      BACKGROUND: SQTS is a rare genetic disorder associated with life-threatening
      arrhythmias, and its natural history is incompletely ascertained. METHODS:
      Seventy-three SQTS patients (84% male; age, 26 +/- 15 years; corrected QT
      interval, 329 +/- 22 ms) were studied, and 62 were followed for 60 +/- 41 months
      (median, 56 months). RESULTS: Cardiac arrest (CA) was the most frequent
      presenting symptom (40% of probands; range, <1 month to 41 years). The rate of CA
      was 4% in the first year of life and 1.3% per year between 20 and 40 years; the
      probability of a first occurrence of CA by 40 years of age was 41%. Despite the
      male predominance, female patients had a risk profile superimposable to that of
      men (p = 0.49). The yield of genetic screening was low (14%), despite familial
      disease being present in 44% of kindreds. A history of CA was the only predictor
      of recurrences at follow-up (p < 0.0000001). Two patterns of onset of ventricular
      fibrillation were observed and were reproducible in patients with multiple
      occurrences of CA. Arrhythmias occurred mainly at rest. CONCLUSIONS: SQTS is
      highly lethal; CA is often the first manifestation of the disease with a peak
      incidence in the first year of life. Survivors of CA have a high CA recurrence
      rate; therefore, implantation of a defibrillator is strongly recommended in this
      group of patients.

PMID- 24291114
TI  - Trend in prevalence of syphilis among voluntary blood donors in Xi'an, China from
      2006 to 2010.
AB  - This study was conducted to examine the prevalence of syphilis among blood donors
      in the Xi'an region of China. All blood donors were unremunerated volunteers
      recruited from 2006 to 2010. Anti-Treponema pallidum and anti-HIV serology
      responses were determined using ELISA kits. Among 159 902 voluntary blood donors
      tested, a total of 575 syphilis (0.36%) and 55 HIV (0.03%) infections were
      identified. While an increasing trend was shown for the prevalence of both
      syphilis and HIV over the 5-year period, there was no statistical correlation
      between the two infections. Our results indicate that syphilis and HIV infections
      are increasing risk factors for the spread of blood-borne infections. Further
      investigations and improvements in blood collection and testing procedures are
      needed to help ensure the safety of donated blood in China. 

PMID- 24291115
TI  - Preoperative variables associated with transfusion requirements in orthotopic
      liver transplantation.
AB  - BACKGROUND: Patients with end-stage chronic liver disease (CLD) and submitted to
      orthotopic liver transplantation (OLT) usually require blood transfusion during
      the procedure or in the post-operative period due to hemorrhage. Risk factors for
      transfusion need are not fully known. This study aimed to identify the factors
      associated with blood components requirements. METHODS: In this retrospective
      study a total of 166 consecutive patients submitted to OLT with the piggyback
      technique, between 2001 and 2011, were evaluated for number of blood components
      transfused during surgical procedure and the four subsequent days (total of 5
      days). We evaluated the association between the number of units transfused and
      clinical variables, such as: Child-Turcotte-Pugh (CTP) and MELD scores,
      hemoglobin concentration (Hb), INR, serum creatinine, bilirubin and albumin
      concentrations, and total, hypothermic and normothermic time of graft ischemia.
      RESULTS: 152 (91.6%) Patients were transfused (median of 24 units of blood
      components). Risk factors for higher blood transfusion requirements were CTP,
      INR, Hb and total time of graft ischemia. The group with CTP-A score received
      less blood components than CTP-B/C (11.5 vs 27; P=0.002). The group with Hb<10
      required a higher number of blood units (34.5 vs 23; P=0.003). The group with
      INR<1.5 received less blood units (20.5 vs 31; P=0.012). The group transplanted
      with a graft exposed to less than the median of 555 min of ischemia received less
      transfusion (21 vs 27; P=0.03). MELD score and the other factors were not
      associated with blood requirements. CONCLUSION: These results demonstrate that
      CTP, but not MELD score, hemoglobin concentration, INR, and total time of graft
      ischemia are preoperative variables associated with blood requirements during OLT
      and in the subsequent days.

PMID- 24291116
TI  - Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions
      and immune responses.
AB  - The innate system's recognition of non-self and danger signals is mediated by a
      limited number of germ-line encoded pattern recognition receptors (PRRs) that
      recognize pathogen associated molecular patterns (PAMPs). Toll-like receptors
      (TLRs) are single, non-catalytic, membrane-spanning PRRs present in invertebrates
      and vertebrates. They act by specifically recognizing PAMPs of a variety of
      microbes and activate signaling cascades to induce innate immunity. A large
      number of TLRs have been identified in various aquatic animals of phyla Cnidaria,
      Annelida, Mollusca, Arthropoda, Echinodermata and Chordata. TLRs of aquatic and
      warm-blooded higher animals exhibit some distinctive features due to their
      diverse evolutionary lineages. However, majority of them share conserve signaling
      pathways in pathogen recognition and innate immunity. Functional analysis of
      novel TLRs in aquatic animals is very important in understanding the comparative
      immunology between warm-blooded and aquatic animals. In additions to innate
      immunity, recent reports have highlighted the additional roles of TLRs in
      adaptive immunity. Therefore, vaccines against many critical diseases of aquatic
      animals may be made more effective by supplementing TLR activators which will
      stimulate dendritic cells. This article describes updated information of TLRs in
      aquatic animals and their structural and functional relationship with warm
      blooded animals. 

PMID- 24291118
TI  - Editorial comment.

PMID- 24291117
TI  - Elevated CD57 and CD95 expressions are associated with lower numbers of CD4+
      recent thymic emigrants in HIV-1 infected immune responders following
      antiretroviral treatment.
AB  - The goal of this study was to understand how immune reconstitution through ART in
      HIV-1 infected patients affects CD4(+) recent thymic emigrants (identified as
      CD31(+) naive T cells). We performed FACS analysis of CD4(+) CD31(+) naive T
      cells from PBMCs in a cross-sectional age-matched cohort, including 25 healthy
      controls (HC), 18 untreated HIV-1 infected viremic progressors (VP), 10 untreated
      HIV-1 infected viral controllers (VC), and 24 HIV-1 infected immune responders
      (IR) following ART. Our data reveal that 37.5% of IR failed to restore their
      CD4(+) CD31(+) naive T cell counts. In addition, significantly higher expressions
      of Ki67, CD57, and CD95 were observed in CD4(+) CD31(+) naive T cells of both VP
      and IR comparing to HC and VC. The significantly elevated CD57 and CD95
      expressions are observed in IR with low CD4(+) CD31(+) naive T cell counts.
      Therefore, our data indicate an incomplete immune reconstitution of CD4(+)
      CD31(+) naive T cells in more than one third of IR, which is associated with HIV
      1 driven immunological phenotypic alterations. 

PMID- 24291119
TI  - Testing the embodied account of object naming: a concurrent motor task affects
      naming artifacts and animals.
AB  - Embodied theories of object representation propose that the same neural networks
      are involved in encoding and retrieving object knowledge. In the present study,
      we investigated whether motor programs play a causal role in the retrieval of
      object names. Participants performed an object-naming task while squeezing a
      sponge with either their right or left hand. The objects were artifacts (e.g.
      hammer) or animals (e.g. giraffe) and were presented in an orientation that
      favored a grasp or not. We hypothesized that, if activation of motor programs is
      necessary to retrieve object knowledge, then concurrent motor activity would
      interfere with naming manipulable artifacts but not non-manipulable animals. In
      Experiment 1, we observed naming interference for all objects oriented towards
      the occupied hand. In Experiment 2, we presented the objects in more 'canonical
      orientations'. Participants named all objects more quickly when they were
      oriented towards the occupied hand. Together, these interference/facilitation
      effects suggest that concurrent motor activity affects naming for both
      categories. These results also suggest that picture-plane orientation interacts
      with an attentional bias that is elicited by the objects and their relationship
      to the occupied hand. These results may be more parsimoniously accounted for by a
      domain-general attentional effect, constraining the embodied theory of object
      representations. We suggest that researchers should scrutinize attentional
      accounts of other embodied cognitive effects. 

PMID- 24291121
TI  - When the mind wanders: age-related differences between young and older adults.
AB  - Interest in mind wandering (MW) has grown in recent years, but few studies have
      assessed this phenomenon in older adults. The aim of this study was to assess age
      related differences between young, young-old and old-old adults in MW using two
      versions of the sustained attention to response task (SART), one perceptual and
      one semantic. Different indicators were examined (i.e., reported MW episodes and
      behavioral indices of MW such as response time latency and variability, incorrect
      response and omission errors). The relationship between MW, certain basic
      mechanisms of cognition (working memory, inhibition and processing speed),
      cognitive failures and intrusive thoughts in everyday life was also explored.
      Findings in both versions of the SART indicated that older adults reported a
      lower frequency of MW episodes than young adults, but some of the behavioral
      indices of MW (response time variability, incorrect response and omission errors)
      were higher in old-old adults. This seems to suggest that MW becomes less
      frequent with aging, but more pervasive and detrimental to performance. Our
      results also indicated that the role of age and cognitive mechanisms in
      explaining MW depends on the demands of the SART task considered. 

PMID- 24291120
TI  - Explicit awareness supports conditional visual search in the retrieval guidance
      paradigm.
AB  - In four experiments we explored whether participants would be able to use
      probabilistic prompts to simplify perceptually demanding visual search in a task
      we call the retrieval guidance paradigm. On each trial a memory prompt appeared
      prior to (and during) the search task and the diagnosticity of the prompt(s) was
      manipulated to provide complete, partial, or non-diagnostic information regarding
      the target's color on each trial (Experiments 1-3). In Experiment 1 we found that
      the more diagnostic prompts was associated with faster visual search performance.
      However, similar visual search behavior was observed in Experiment 2 when the
      diagnosticity of the prompts was eliminated, suggesting that participants in
      Experiment 1 were merely relying on base rate information to guide search and
      were not utilizing the prompts. In Experiment 3 participants were informed of the
      relationship between the prompts and the color of the target and this was
      associated with faster search performance relative to Experiment 1, suggesting
      that the participants were using the prompts to guide search. Additionally, in
      Experiment 3 a knowledge test was implemented and performance in this task was
      associated with qualitative differences in search behavior such that participants
      that were able to name the color(s) most associated with the prompts were faster
      to find the target than participants who were unable to do so. However, in
      Experiments 1-3 diagnosticity of the memory prompt was manipulated via base rate
      information, making it possible that participants were merely relying on base
      rate information to inform search in Experiment 3. In Experiment 4 we manipulated
      diagnosticity of the prompts without manipulating base rate information and found
      a similar pattern of results as Experiment 3. Together, the results emphasize the
      importance of base rate and diagnosticity information in visual search behavior.
      In the General discussion section we explore how a recent computational model of
      hypothesis generation (HyGene; Thomas, Dougherty, Sprenger, & Harbison, 2008),
      linking attention with long-term and working memory, accounts for the present
      results and provides a useful framework of cued recall visual search. 

PMID- 24291122
TI  - Genetic susceptibility to multicase hypersensitivity pneumonitis is associated
      with the TNF-238 GG genotype of the promoter region and HLA-DRB1*04 bearing HLA
      haplotypes.
AB  - Hypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by
      inhalation of organic particles by a susceptible host. Since only a small
      proportion of individuals exposed to HP-related antigens develop the disease, a
      genetic predisposition is largely suspected. However, studies regarding genetic
      susceptibility in this disease are scanty. We have previously found evidence
      supporting increased risk associated to the major histocompatibility complex
      (MHC) in sporadic HP. In the present study, we conducted a family-based research
      that includes nine multicase families with at least two related HP patients
      (RHP). We evaluated 19 RHP individuals, 25 additional healthy first-degree
      relatives (REA) and 246 healthy unrelated individuals (HUI). HLA class II typing
      (DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1, DMA and DMB), and -863, -308 and -238
      polymorphisms in the promoter region of TNF-alpha were performed by PCR based
      methods. We identified an increased frequency of HLA-DRB1*04:07, DRB1*04:05,
      DRB1*11:01 and DRB1*13:01 alleles in RHP individuals compared to healthy controls
      (p < 0.05). A significant higher frequency of DRB1*04:07-DQB1*03:02, DRB1*04:05
      DQB1*03:02, and DRB1*04:03-DQB1*03:02 haplotypes was also detected in the group
      of patients. Likewise, TNF-238 GG genotype was more frequent in the RHP group as
      compared to REA (p = 0.01, OR = 7.2). Finally, the combination of HLA-DRB1*04
      alleles and TNF-238 GG was significantly increased in the RHP group (p = 0.01, OR
      = 6.93). These findings indicate that genes located within the MHC region confer
      susceptibility to familial HP in Mexicans. 

PMID- 24291123
TI  - A mechanistic based approach for enhancing buccal mucoadhesion of chitosan.
AB  - Mucoadhesive buccal drug delivery systems can enhance rapid drug absorption by
      providing an increased retention time at the site of absorption and a steep
      concentration gradient. An understanding of the mechanisms behind mucoadhesion of
      polymers, e.g. chitosan, is necessary for improving the mucoadhesiveness of
      buccal formulations. The interaction between chitosan of different chain lengths
      and porcine gastric mucin (PGM) was studied using a complex coacervation model
      (CCM), isothermal titration calorimetry (ITC) and a tensile detachment model
      (TDM). The effect of pH was assessed in all three models and the approach to add
      a buffer to chitosan based drug delivery systems is a means to optimize and
      enhance buccal drug absorption. The CCM demonstrated optimal interactions between
      chitosan and PGM at pH 5.2. The ITC experiments showed a significantly increase
      in affinity between chitosan and PGM at pH 5.2 compared to pH 6.3 and that the
      interactions were entropy driven. The TDM showed a significantly increase in
      strength of adhesion between chitosan discs and an artificial mucosal surface at
      pH 5.2 compared to pH 6.8, addition of PGM increased the total work of adhesion
      by a factor of 10 as compared to the wetted surface without PGM. These findings
      suggest that chitosan and PGM are able to interact by electrostatic interactions
      and by improving the conditions for electrostatic interactions, the adhesion
      between chitosan and PGM becomes stronger. Also, the three complementary methods
      were utilized to conclude the pH dependency on mucoadhesiveness. 

PMID- 24291124
TI  - The impact of pulmonary diseases on the fate of inhaled medicines--a review.
AB  - The portfolio of compounds approved for inhalation therapy has expanded rapidly
      for treatment of lung diseases. To assess the efficacy and safety of inhaled
      medicines, a better understanding of their fate in the lungs is essential;
      especially in diseased lungs where changes in anatomical structure, ventilation
      parameters and breathing pattern may occur. In this article, the impact of lung
      pathophysiology factors on the fate of inhaled medicines is reviewed, and
      discussed in the context of aerosol deposition, dissolution, absorption and
      clearance. Special emphasis is given to computational modeling of aerosol
      deposition and clearance taking disease factors into consideration. In silico
      modeling can be used as a valuable tool to characterize the biopharmaceutics and
      pharmacodynamics of inhaled medicines, or assess risks associated with inhaled
      environmental pollutants for patients with pulmonary diseases. The deposition
      pattern of aerosol particles is greatly altered by different lung diseases based
      on both experimental data and model simulation. The fate of inhaled medicines
      after deposition primarily depends on the site of aerosol deposition. Therefore,
      when developing inhalation products for treatment of lung diseases, the dosing
      regimen, safety and pharmacokinetic studies should be conducted on patients with
      lung diseases, in addition to healthy subjects. 

PMID- 24291125
TI  - Development and validation of a lateral flow assay (LFA) for the determination of
      IgG-antibodies to Pr3 (cANCA) and MPO (pANCA).
AB  - The timely diagnosis of vasculopathies, such as granulomatosis with polyangiitis,
      has important implications for the favorable clinical outcome of these diseases.
      In the clinical setting, autoantibodies to proteinase 3 (Pr3) and myeloperoxidase
      (MPO) have been shown to be valuable adjuncts to an early and accurate diagnosis.
      The sensitive and specific detection of anti-Pr3 and anti-MPO was shown using a
      point of care device that employed rapid Lateral Flow Technologies. The
      validation of the lateral flow assay (LFA) was performed with serum samples
      collected in two Reference Laboratories and showed excellent results that were
      comparable to widely accepted and used ELISA. The advantage of the LFA is the
      flexibility to be used as an economical, point of care diagnostic device,
      features that are especially important for an early and accurate diagnosis and
      the prompt initiation of appropriate treatment so as to avoid inevitable
      development of undue complications of these diseases such as disseminated organ
      involvement, e.g. renal failure. 

PMID- 24291127
TI  - Diverse functions of PHD fingers of the MLL/KMT2 subfamily.
AB  - Five members of the KMT2 family of lysine methyltransferases, originally named
      the mixed lineage leukemia (MLL1-5) proteins, regulate gene expression during
      embryogenesis and development. Each KMT2A-E contains a catalytic SET domain that
      methylates lysine 4 of histone H3, and one or several PHD fingers. Over the past
      few years a growing number of studies have uncovered diverse biological roles of
      the KMT2A-E PHD fingers, implicating them in binding to methylated histones and
      other nuclear proteins, and in mediating the E3 ligase activity and dimerization.
      Mutations in the PHD fingers or deletion of these modules are linked to human
      diseases including cancer and Kabuki syndrome. In this work, we summarize
      recently identified biological functions of the KMT2A-E PHD fingers, discuss
      mechanisms of their action, and examine preference of these domains for histone
      and non-histone ligands. 

PMID- 24291129
TI  - Ambient polychlorinated biphenyl levels and their evaluation in a metropolitan
      city.
AB  - In this study, summer and autumn ambient PCB concentrations were investigated in
      metropolitan city of Istanbul. 84 congeners were targeted from di-CBs to nona-CBs
      on both particle and gaseous phases. Gaseous ambient concentrations were
      determined to be 372 +/- 134 pg.m(-3), while on the particle phase this value was
      49 +/- 17 pg.m(-3), corresponding to an average of 420 pg.m(-3). About one-tenth
      of all PCBs lay in ambient aerosols, while 90% of all comprise 2-, 3-, 4-, and 5
      CBs. Measured ambient concentrations of each congener group were tested against
      meteorological data. The di-CB concentrations were independent of ambient
      temperature while northerly winds lead to an increase in their concentrations,
      which was an indicator of considerable contribution to di-CB concentrations from
      the medical waste incineration plant in Istanbul. In contrast, other congeners'
      concentrations were found to be correlated with southerly winds. Being an inland
      sea and having been contaminated, for years, by industrial discharges along the
      coastline, volatilization from Marmara Sea was considered as the most probable
      source of other congeners. PSCF analysis was run with 12-hour trajectories to
      locate possible local sources and check these results. Gas/particle partitioning
      was applied using three different models. mr and br values for log PL(0) model
      were determined as -0.23 +/- 0.09 and -3.25 +/- 0.38, respectively. For
      absorption based log Koa model, m and b values were calculated as 0.23 +/- 0.08
      and -4.73 +/- 0.83, respectively.

PMID- 24291128
TI  - Pilot survey of methamphetamine in sewers using a Polar Organic Chemical
      Integrative Sampler.
AB  - A pilot study for the qualitative detection of methamphetamine at sites within a
      sewage collection system adjacent to locations suspected to harbor illegal drug
      activities was investigated and preliminary findings are reported. Sewage samples
      were collected over a time interval of four weeks using a Polar Organic Chemical
      Integrative Sampler (POCIS) deployed directly into the sewer line. The POCIS
      sorbent was extracted and analyzed via high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS). Methamphetamine was found in sewage from
      one of three sampling sites at a concentration greater than the HPLC-MS/MS method
      detection limit (MDL) of 3 ng/mL. The goal of this research was to establish
      proof-of-concept of the feasibility for sampling and analysis using POCIS devices
      in the sewage collection system. The data encourage further testing and research.
      The ability to pinpoint the presence of methamphetamine in the sewer may in the
      future be used as a forensic tool in law enforcement.

PMID- 24291126
TI  - Development of a luciferase based viral inhibition assay to evaluate vaccine
      induced CD8 T-cell responses.
AB  - Emergence of SIV and HIV specific CD8 T cells has been shown to correlate with
      control of in vivo replication. Poor correlation between IFN-gamma ELISPOT
      responses and in vivo control of the virus has triggered the development of more
      relevant assays to assess functional HIV-1 specific CD8 T-cell responses for the
      evaluation and prioritization of new HIV-1 vaccine candidates. We previously
      established a viral inhibition assay (VIA) that measures the ability of vaccine
      induced CD8 T-cell responses to inhibit viral replication in autologous CD4 T
      cells. In this assay, viral replication is determined by measuring p24 in the
      culture supernatant. Here we describe the development of a novel VIA, referred to
      as IMC LucR VIA that exploits replication-competent HIV-1 infectious molecular
      clones (IMCs) in which the complete proviral genome is strain-specific and which
      express the Renilla luciferase (LucR) gene to determine viral growth and
      inhibition. The introduction of the luciferase readout does provide significant
      improvement of the read out time. In addition to switching to the LucR read out,
      changes made to the overall protocol resulted in the miniaturization of the assay
      from a 48 to a 96-well plate format, which preserved sample and allowed for the
      introduction of replicates. The overall assay time was reduced from 13 to 8 days.
      The assay has a high degree of specificity, and the previously observed non
      specific background inhibition in cells from HIV-1 negative volunteers has been
      reduced dramatically. Importantly, we observed an increase in positive responses,
      indicating an improvement in sensitivity compared to the original VIA. Currently,
      only a limited number of "whole-genome" IMC-LucR viruses are available and our
      efforts will focus on expanding the panel to better evaluate anti-viral breadth.
      Overall, we believe the IMC LucR VIA provides a platform to assess functional CD8
      T-cell responses in large-scale clinical trial testing, which will enhance the
      ability to select the most promising HIV-1 vaccine candidates capable of
      controlling HIV-1 replication in vivo.

PMID- 24291130
TI  - Dispersive infrared spectroscopy measurements of atmospheric CO2 using a Fabry
      Perot interferometer sensor.
AB  - In this paper, we present the first dispersive infrared spectroscopic (DIRS)
      measurement of atmospheric carbon dioxide (CO2) using a new scanning Fabry-Perot
      interferometer (FPI) sensor. The sensor measures the optical spectra in the mid
      infrared (3,900 nm to 5,220 nm) wavelength range with full width half maximum
      (FWHM) spectral resolution of 78.8 nm at the CO2 absorption band (~4,280 nm) and
      sampling resolution of 20 nm. The CO2 concentration is determined from the
      measured optical absorption spectra by fitting it to the CO2 reference spectrum.
      Interference from other major absorbers in the same wavelength range, e.g.,
      carbon monoxide (CO) and water vapor (H2O), was taken out by including their
      reference spectra in the fit as well. The detailed descriptions of the
      instrumental setup, the retrieval procedure, a modeling study for error analysis
      as well as laboratory validation using standard gas concentrations are presented.
      An iterative algorithm to account for the non-linear response of the fit function
      to the absorption cross sections due to the broad instrument function was
      developed and tested. A modeling study of the retrieval algorithm showed that
      errors due to instrument noise can be considerably reduced by using the
      dispersive spectral information in the retrieval. The mean measurement error of
      the prototype DIRS CO2 measurement for 1 minute averaged data is about +/-2.5
      ppmv, and down to +/- 0.8ppmv for 10 minute averaged data. A field test of
      atmospheric CO2 measurements were carried out in an urban site in Hong Kong for a
      month and compared to a commercial non-dispersive infrared (NDIR) CO2 analyzer.
      10 minute averaged data shows good agreement between the DIRS and NDIR
      measurements with Pearson correlation coefficient (R) of 0.99. This new method
      offers an alternative approach of atmospheric CO2 measurement featuring high
      accuracy, correction of non-linear absorption and interference of water vapor.

PMID- 24291131
TI  - Lysosomal and tissue-level biomarkers in mussels cross-transplanted among four
      estuaries with different pollution levels.
AB  - A 3-4 wk cross-transplantation experiment was carried out in order to investigate
      the sensitivity, rapidity, durability and reversibility of lysosomal and tissue
      level biomarkers in the digestive gland of mussels. Four localities in the Basque
      coast with different levels of chemical pollution and environmental stress were
      selected. Lysosomal membrane stability (LP) and lysosomal structural changes
      (VvL; S/VL; NvL) and changes in cell-type composition in digestive gland
      epithelium (VvBAS) were investigated to determine short (2d) and mid-term (3-4
      wk) responses after cross-transplantation. Mussels from Txatxarramendi presented
      VvBAS<0.1 MUm(3)/MUm(3) (unstressed) whilst VvBAS>0.12 MUm(3)/MUm(3) was recorded
      in mussels from Plentzia (moderate stress) and VvBAS>0.2 MUm(3)/MUm(3) in
      Arriluze and Muskiz (high stress). Accordingly, LP<10 min (high stress) was
      recorded in mussels from Muskiz and Arriluze and LP~15 min (low-to-moderate
      stress) in those from Plentzia and Txatxarramendi. According to the VvL, S/VL and
      NvL data, a certain lysosomal enlargement was envisaged in mussels from Arriluze
      in comparison with those from Txatxarramendi and Plentzia. Mussels from Muskiz
      exhibited a peculiar endo-lysosomal system made of abundant tiny lysosomes (low
      VvL and high S/VL and NvL values). Lysosomal and tissue-level biomarkers were
      responsive after 2d cross-transplantation between the reference and the polluted
      localities, which indicated that these biomarkers were quickly induced and, to a
      large extent, reversible. Moreover, the tissue-level biomarker values were
      maintained during the entire period (3-4 wk) of cross-transplantation, which
      evidenced the durability of the responsiveness. In contrast, comparisons in the
      mid-term were unfeasible for lysosomal biomarkers as these exhibited a seasonal
      winter attenuation resulting from low food availability and low temperatures. In
      conclusion, lysosomal enlargement and membrane stability and changes in cell-type
      composition were sensitive, rapid and reversible responses to changes in
      environmental stress whilst durability of the response could not be demonstrated
      for lysosomal responses by interferences with the seasonal variability.

PMID- 24291132
TI  - Urinary phthalate metabolites among elementary school children of Korea: sources,
      risks, and their association with oxidative stress marker.
AB  - Phthalates have been used in a variety of consumer products and hence frequently
      been detected in humans. Children are susceptible to endocrine disrupting
      chemicals such as phthalates, but only limited information is available on the
      sources of exposure and potential adverse health effects among children. In this
      study, elementary school students (n=39, aged 9-12 years) were recruited in
      Seoul, and first void urine samples were collected twice in three-day intervals.
      Then six phthalate metabolites were analyzed by high performance liquid
      chromatography with triple quadrupole tandem mass spectrometry. In addition,
      malondialdehyde (MDA) as an oxidative stress marker was measured. A questionnaire
      was conducted and information on food consumption and the use of plastic
      packaging or storage materials was gathered. The concentrations of phthalate
      metabolites varied substantially by sampling time even within the same subject,
      but all target metabolites were detected in 100% of the samples with the highest
      geometric mean of 107 MUg/g-creatinine for mono-n-butyl phthalate (MnBP). Urinary
      levels of mono-isobutyl phthalate (MiBP), and MnBP among Korean children were 8
      and 3 times greater than those reported for US children, but those of monoethyl
      phthalate (MEP) were about 5 times lower than those of US children. Estimated
      phthalate intakes were generally in safe range, but in 3-8% of the participating
      children, the hazard quotients greater than one were noted. Urinary MDA
      concentrations were significantly associated with several metabolite levels after
      adjusting covariates in regression model. Consumption of dairy products or meat,
      and use of a plastic material were significantly associated with the DEHP
      metabolites or MnBP levels in multivariate model. The results of this study
      provide evidence of the association between phthalate exposure and oxidative
      stress especially among the early teenagers, and identified major sources that
      can be applied to development of management plan for phthalate exposure among
      children.

PMID- 24291133
TI  - Applying consequential LCA to support energy policy: land use change effects of
      bioenergy production.
AB  - Luxembourg aims at complying with the EU objective of attaining a 14% use of
      bioenergy in the national grid by 2020. The increase of biomethane production
      from energy crops could be a valuable option in achieving this objective.
      However, the overall environmental benefit of such option is yet to be proven.
      Consequential Life Cycle Assessment (CLCA) has shown to be a useful tool to
      evaluate the environmental suitability of future energy scenarios and policies.
      The objective of this study was, therefore, to evaluate the environmental
      consequences of modifying the Luxembourgish agricultural system to increase maize
      production for biomethane generation. A total of 10 different scenarios were
      modelled using a partial equilibrium (PE) model to identify changes in land
      cultivation based on farmers' revenue maximisation, which were then compared to
      the baseline scenario, i.e. the state of the agricultural sector in 2009. The
      results were divided into three different consequential decision contexts,
      presenting differing patterns in terms of land use changes (LUCs) but with minor
      shifts in environmental impacts. Nevertheless, energy from maize production would
      imply substantially higher environmental impacts when compared with the current
      use of natural gas, mainly due to increases in climate change and agricultural
      land occupation impacts. The results are discussed based on the consequences they
      may generate on the bioenergy policy, the management of arable land, the changes
      in import-export flows in Luxembourg and LUCs in the domestic agricultural
      system. In addition, the specific PE+LCA method presented intends to be of use
      for other regional studies in which a high level of site-specific data is
      available.

PMID- 24291134
TI  - Bacterial community of biofilms developed under different water supply conditions
      in a distribution system.
AB  - In order to understand the bacterial community characteristics of biofilms
      developed under different finished water supply histories in drinking water
      distribution systems (DWDS), biofilm samples on different type of iron corrosion
      scales in a real DWDS were collected and systematically investigated using 454
      pyrosequencing of 16S rRNA gene. The richness and diversity estimators showed
      that biofilms formed in DWDS transporting finished groundwater (GW) had the
      lowest level of bacterial diversity. From phylum to genus level, the dominant
      bacterial groups found in the biofilms under finished surface water (SW) and GW
      conditions were distinct. Proteobacteria was the dominant group in all biofilm
      samples (in the range of 40%-97%), but was relatively higher in biofilms with GW.
      The relative abundance of Firmicutes in biofilms with SW (28%-35%) was
      significantly higher (p<0.01) than that in biofilms with GW (0.5%-2.88%).
      Statistical analysis (Spearman's rank) revealed that alkalinity and chemical
      oxygen demand (CODMn) positively correlated with the relative abundance of
      Proteobacteria and Firmicutes, respectively. The abundance of sequences
      affiliated to iron-reducing bacteria (mainly Bacillus) and iron-oxidizing
      bacteria (mainly Acidovorax) were relatively higher in biofilms with SW, which
      might contribute to the formation of much thicker or tubercle-formed corrosion
      scales under SW supply condition. Several potential opportunistic pathogens, such
      as Burkholderia fungorum, Mycobacterium neoaurum, Mycobacterium frederiksbergense
      were detected in the biofilms.

PMID- 24291135
TI  - Antihistamines and aquatic insects: bioconcentration and impacts on behavior in
      damselfly larvae (Zygoptera).
AB  - Because aquatic insects use histamines as neurotransmitters, adverse impacts on
      aquatic insects living in aquatic environments that receive antihistamines with
      wastewater effluent are plausible. In this study, we exposed damselfly larvae to
      low concentrations of two commonly used antihistamines (Hydroxyzine and
      Fexofenadine, 360 +/- 42 and 2,200 +/- 43 ng l(-1), respectively), and recorded
      damselfly larvae behavior before and after exposure. Further, after the second
      set of behavioral assays was performed, we quantified bioconcentration of the
      antihistamines in the damselfly bodies. Our results showed significant changes in
      damselfly behavior following antihistamine exposure. After Hydroxyzine exposure,
      the damselfly larvae became less active, and they showed reduced fleeing response
      (i.e. increased boldness) after being exposed to Fexofenadine, the latter also
      being significantly different from the non-exposed (control) individuals.
      Further, we found high levels of bioconcentration in the damselflies; Hydroxyzine
      showed an average bioconcentration factor (BCF) of 2000. As such, our results
      indicate that low concentrations of antihistamines can have sub-lethal effects on
      aquatic insects manifested as behavioral changes, and that bioconcentration of
      these substances can be high. Therefore, the need to investigate the impact of
      emergent aquatic contaminants also on aquatic insects, and on behaviors that are
      of ecological importance, is further highlighted.

PMID- 24291136
TI  - Nitrous oxide and methane emissions from optimized and alternative cereal
      cropping systems on the North China Plain: a two-year field study.
AB  - The impacts of different crop rotation systems with their corresponding
      management practices on grain yield, greenhouse gas emissions, and fertilizer
      nitrogen (N) and irrigation water use efficiencies are not well documented. This
      holds especially for the North China Plain which provides the staple food for
      hundreds of millions of people and where groundwater resources are polluted with
      nitrate and depleted through irrigation. Here, we report on fertilizer N and
      irrigation water use, grain yields, and nitrous oxide (N2O) and methane (CH4)
      emissions of conventional and optimized winter wheat-summer maize double-cropping
      systems, and of three alternative cropping systems, namely a winter wheat-summer
      maize (or soybean)-spring maize system, with three harvests in two years; and a
      single spring maize system with one crop per year. The results of this two-year
      study show that the optimized double-cropping system led to a significant
      increase in grain yields and a significant decrease in fertilizer N use and net
      greenhouse gas intensity, but the net greenhouse gas N2O emissions plus CH4
      uptake and the use of irrigation water did not decrease relative to the
      conventional system. Compared to the conventional system the net greenhouse gas
      emissions, net greenhouse gas intensity and use of fertilizer N and irrigation
      water decreased in the three alternative cropping systems, but at the cost of
      grain yields except in the winter wheat-summer maize-spring maize system. Net
      uptake of CH4 by the soil was little affected by cropping system. Average N2O
      emission factors were only 0.17% for winter wheat and 0.53% for maize. In
      conclusion, the winter wheat-summer maize-spring maize system has considerable
      potential to decrease water and N use and decrease N2O emissions while
      maintaining high grain yields and sustainable use of groundwater. 

PMID- 24291137
TI  - The Minamata Convention on Mercury: attempting to address the global controversy
      of dental amalgam use and mercury waste disposal.
AB  - In October 2013, a new international binding treaty instrument called the
      Minamata Convention on Mercury opened for signature in Minamata City, Japan, the
      site of arguably the worst public health and environmental disaster involving
      mercury contamination. The treaty aims to curb the significant health and
      environmental impacts of mercury pollution and includes provisions addressing the
      mining, export and import, storage, and waste management of products containing
      mercury. Importantly, a provision heavily negotiated in the treaty addresses the
      use of dental fillings using mercury amalgam, an issue that has been subject to
      decades of global controversy. Though use of dental amalgam is widespread and has
      benefits, concerns have been raised regarding the potential for human health risk
      and environmental damage from emissions and improper waste management. While the
      Minamata Convention attempts to address these issues by calling for a voluntary
      phase-down of dental amalgam use and commitment to other measures, it falls short
      by failing to require binding and measurable targets to achieve these goals. In
      response, the international community should begin exploring ways to strengthen
      the implementation of the dental amalgam treaty provisions by establishing
      binding phase-down targets and milestones as well as exploring financing
      mechanisms to support treaty measures. Through strengthening of the Convention,
      stakeholders can ensure equitable access to global oral health treatment while
      also promoting responsible environmental stewardship. 

PMID- 24291138
TI  - Photodegradation of parabens by Fe(III)-citrate complexes at circumneutral pH:
      matrix effect and reaction mechanism.
AB  - The photodegradation of four parabens including methyl-, ethyl-, propyl-, and
      butyl-paraben in the presence of Fe(III)-citrate complexes under simulated
      sunlight was investigated. The degradation of parabens increased with decreasing
      pH within the range of 5.0-8.0 at the Fe(III)-to-citrate ratio of 10:150 (MUM).
      The addition of low-molecular-weight carboxylic acids showed different effects on
      the photodegradation of methylparaben. The low-photoreactive carboxylic acids
      inhibited the photodegradation of methylparaben in the order of formic
      acid>succinic acid>acetic acid>malonic acid. In contrast, oxalic acid enhanced
      the photodegradation and exhibited appreciable synergistic effect with Fe(III)
      citrate at concentration higher than 500 MUM. Up to 99.0% of substrate was
      degraded after 30 min at pH6.0 in the Fe(III)-citrate-oxalate system. The various
      fractions of fulvic acid inhibited the photodegradation of methylparaben. The
      inhibition increased with increasing nominal molecular weight of fractionated
      fulvic acid. Moreover, the photodegradation of methylparaben was inhibited in
      natural waters in the order of Liangzi Lake<Donghu Lake<Changjiang
      River~Seawater. The photoproducts of methylparaben were identified by GC-MS
      analyses and the degradation pathway was proposed.

PMID- 24291139
TI  - Analysis of the ecotoxicity data submitted within the framework of the REACH
      Regulation. Part 2. Experimental aquatic toxicity assays.
AB  - This paper summarises the aquatic ecotoxicity data submitted in the REACH(1)
      registration dossiers and disseminated by the European Chemicals Agency
      (ECHA(2)). The analysis describes both the guidelines and the species mostly used
      by registrants. Non-OECD guidelines have been extensively used, in particular in
      covering of fish and aquatic invertebrate studies, but the main concern is that
      in 22-36% of the cases, depending on the endpoint, no information on the
      methodological approach and potential equivalences to test guidelines has been
      provided. As expected, most studies were conducted with those species typically
      used in laboratory ecotoxicity testing; nevertheless, the database provides a
      broad range of available species, covering the most relevant taxonomic groups for
      both freshwater and marine systems, although most are just occasionally used.
      This species diversity is essential for higher tier testing strategies, including
      the use of Species Sensitivity Distribution approaches. The assessment suggests
      that collecting available information has been the main approach used by
      registrants to fulfil their REACH information requirements for this first REACH
      registration deadline. Many studies are disclosed for the first time, and all are
      available through searchable web tools. 

PMID- 24291140
TI  - Assessment of the exposure to organochlorine pesticides, PCBs and PAHs in six
      species of predatory birds of the Canary Islands, Spain.
AB  - In the present study, we investigated the concentrations and distributions of 57
      anthropogenic pollutants, including 23 organochlorine pesticides (OCs), 18
      polychlorinated biphenyls (PCBs) and 16 polycyclic aromatic hydrocarbons (PAHs)
      in liver samples from 102 birds of prey of six species that were found dead or
      that had died during their stay in the Wildlife Recovery Centers of the Canary
      Islands (Spain) between 2009 and 2012. The dual goal of this work was to
      determine the occurrence of these contaminants in these six species of birds of
      prey, and also whether they can be used as bioindicators for monitoring
      environmental pollution in the region. We found that Accipiter nisus, Falco
      pelegrinoides and Falco tinnunculus were the most contaminated species. The
      profiles of contamination among the species were extremely similar in the case of
      organochlorine contaminants, with DDT and its metabolites as the most abundant
      compounds. The contamination by DDT and its metabolites, as well as contamination
      by dieldrin, could be considered high in these animals, much higher than reports
      from other regions of the planet, which is in agreement with previous reports
      from our group regarding humans, food and other animals from this area. In
      contrast, the contamination by PCBs could be considered extremely low and was
      probably below the threshold of toxicity for these contaminants. The content of
      carcinogenic/mutagenic PAHs in these animals was clearly dependent on the feeding
      pattern of the species; however, the levels were also well below the values that
      were considered toxic in predictive models. This study represents the first
      report of contamination by PAHs in all these species and is also the first report
      of PCB levels in Barbary Falcons.

PMID- 24291141
TI  - Influence of hydrologic and anthropogenic factors on the abundance variability of
      enteropathogens in the Ganges estuary, a cholera endemic region.
AB  - This study deals with the influence of water physico-chemical properties, tides,
      rainfall and fecal pollution on the abundance of enteropathogens in a main
      distributary of the Ganges, in the endemic cholera belt of West Bengal. Between
      January and June 2011, water and sediments were sampled from two sites of the
      Hooghly River by Kolkata and Diamond Harbour. Counts of cultivable Vibrio (CVC,
      from~10(2) to~10(5)CFU/L) and total bacteria (TBC, from~10(5) to~10(9)CFU/L)
      increased with water temperature (17 degrees C to 37 degrees C). A combination of
      variations in tidal height, salinity and turbidity had a distinct influence on
      CVC, TBC and coliform counts. At Diamond Harbour, a salinity increase from 0.6 to
      7.9 was accompanied by a 1000-fold amplification of initial CVC~10(2)CFU/L,
      whereas higher prevalence of coliforms in Kolkata was related to greater disposal
      of untreated sewage into the river. Turbidity-dependent variation of CVC was
      noteworthy, particularly at Diamond Harbour, where CVC in intertidal surface
      sediments showed an analogous trend as in surface waters, suggesting bentho
      pelagic coupling of Vibrio dynamics. Besides the influence of salinity variation
      with tidal cycles, sediment re-suspension from tidal flats can play a role on
      Vibrio abundance in aquatic ecosystems.

PMID- 24291142
TI  - Honey in wound management: myth, mystery, magic or marvel?

PMID- 24291143
TI  - Advanced oxidation protein products are generated by bovine neutrophils and
      inhibit free radical production in vitro.
AB  - Despite the recognised importance of oxidative stress in the health and immune
      function of dairy cows, protein oxidation markers have been poorly studied in
      this species. The current study aimed to characterise markers of protein
      oxidation generated by activated bovine neutrophils and investigate the
      biological effects of advanced oxidation protein products (AOPP) on bovine
      neutrophils. Markers of protein oxidation (AOPP, dityrosines and carbonyls) were
      measured in culture medium containing bovine serum albumin (BSA) exposed to
      neutrophils. The effect of AOPP-BSA on generation of reactive oxygen species
      (ROS) was assessed by chemiluminescence. Activation of caspases-3, -8 and -9 and
      the presence of DNA laddering were used as apoptosis markers. Greater amounts of
      AOPP were generated by phorbol myristate acetate (PMA)-activated than non
      activated neutrophils (1.46 +/- 0.13 vs. 0.75 +/- 0.13 nmol/mg protein,
      respectively; P<0.05). Activated neutrophils and hypochlorous acid generated
      slightly different patterns of oxidized protein markers. Exposure to AOPP-BSA did
      not stimulate ROS production. Activated neutrophils generated a lesser amount of
      ROS when incubated with AOPP-BSA (P<0.001). Activation with PMA induced a loss of
      viable neutrophils after 3h, which was greater with AOPP-BSA incubation (P<0.05).
      Detectable amounts of active caspases-3, -8 and -9 were found in nearly all
      samples but differences in caspase activation or DNA laddering were not observed
      comparing treatment groups. Apoptosis was unlikely to be responsible for the
      greater loss of PMA-activated neutrophils cultured in AOPP-BSA and it is possible
      that primary necrosis occurred. The results suggest that accumulation of oxidized
      proteins at an inflammatory site might result in a progressive reduction of
      neutrophil viability.

PMID- 24291144
TI  - Asystole in alternating hemiplegia with de novo ATP1A3 mutation.
AB  - Alternating hemiplegia is a rare condition presenting with episodes of
      hemiplegia, epileptic seizures and, at times, dysautonomic attacks. De novo
      ATP1A3 (Na(+)/K(+) ATPase subunit) mutations were recently found to be the most
      common cause. We report a patient with alternating hemiplegia with de novo ATP1A3
      mutation who experienced new-onset episodes of collapse in early adulthood
      unrelated to seizures. An implantable cardiac loop recorder documented episodes
      of asystole up to 5 s long. Subsequently a permanent pacemaker was implanted.
      ATP1A3 heart expression may be the explanation for the association of alternating
      hemiplegia and asystole episodes. Alternating hemiplegia has been associated with
      an increased risk of sudden death and lethal cardiac arrhythmias may be
      causative. Patients may need referral for appropriate cardiac investigations,
      especially if there is a change in symptoms. This case highlights the importance
      of clinical vigilance in patients with alternating hemiplegia. 

PMID- 24291145
TI  - A conceptual model of verbal exchange health literacy.
AB  - OBJECTIVE: To address a gap in understanding of verbal exchange (oral and aural)
      health literacy by describing the systematic development of a verbal exchange
      health literacy (VEHL) definition and model which hypothesizes the role of VEHL
      in health outcomes. METHODS: Current health literacy and communication literature
      was systematically reviewed and combined with qualitative patient and provider
      data that were analyzed using a grounded theory approach. RESULTS: Analyses of
      current literature and formative data indicated the importance of verbal exchange
      in the clinical setting and revealed various factors associated with the patient
      provider relationship and their characteristics that influence decision making
      and health behaviors. VEHL is defined as the ability to speak and listen that
      facilitates exchanging, understanding, and interpreting of health information for
      health-decision making, disease management and navigation of the healthcare
      system. A model depiction of mediating and influenced factors is presented.
      CONCLUSION: A definition and model of VEHL is a step toward addressing a gap in
      health literacy knowledge and provides a foundation for examining the influence
      of VEHL on health outcomes. PRACTICE IMPLICATIONS: VEHL is an extension of
      current descriptions of health literacy and has implications for patient-provider
      communication and health decision making.

PMID- 24291146
TI  - Human TREX2 components PCID2 and centrin 2, but not ENY2, have distinct functions
      in protein export and co-localize to the centrosome.
AB  - TREX-2 is a five protein complex, conserved from yeast to humans, involved in
      linking mRNA transcription and export. The centrin 2 subunit of TREX-2 is also a
      component of the centrosome and is additionally involved in a distinctly
      different process of nuclear protein export. While centrin 2 is a known
      multifunctional protein, the roles of other human TREX-2 complex proteins other
      than mRNA export are not known. In this study, we found that human TREX-2 member
      PCID2 but not ENY2 is involved in some of the same cellular processes as those of
      centrin 2 apart from the classical TREX-2 function. PCID2 is present at the
      centrosome in a subset of HeLa cells and this localization is centrin 2
      dependent. Furthermore, the presence of PCID2 at the centrosome is prevalent
      throughout the cell cycle as determined by co-staining with cyclins E, A and B.
      PCID2 but not ENY2 is also involved in protein export. Surprisingly, siRNA
      knockdown of PCID2 delayed the rate of nuclear protein export, a mechanism
      distinct from the effects of centrin 2, which when knocked down inhibits export.
      Finally we showed that co-depletion of centrin 2 and PCID2 leads to blocking
      rather than delaying nuclear protein export, indicating the dominance of the
      centrin 2 phenotype. Together these results represent the first discovery of
      specific novel functions for PCID2 other than mRNA export and suggest that
      components of the TREX-2 complex serve alternative shared roles in the regulation
      of nuclear transport and cell cycle progression. 

PMID- 24291147
TI  - Quantitative developmental transcriptomes of the sea urchin Strongylocentrotus
      purpuratus.
AB  - Development depends on the precise control of gene expression in time and space.
      A critical step towards understanding the global gene regulatory networks
      underlying development is to obtain comprehensive information on gene expression.
      In this study, we measured expression profiles for the entire expressed gene set
      during sea urchin embryonic development. We confirmed the reliability of these
      profiles by comparison with NanoString measurements for a subset of genes and
      with literature values. The data show that ~16,500 genes have been activated by
      the end of embryogenesis, and for half of them the transcript abundance changes
      more than 10-fold during development. From this genome scale expression survey,
      we show that complex patterns of expression by many genes underlie embryonic
      development, particularly during the early stages before gastrulation. An
      intuitive web application for data query and visualization is presented to
      facilitate use of this large dataset. 

PMID- 24291148
TI  - Rapid detection of duck hepatitis A virus genotype C using reverse transcription
      loop-mediated isothermal amplification.
AB  - A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP)
      assay was used and optimized to develop a rapid and sensitive detection system
      for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific
      primers was designed against highly conserved sequences located within the 3D
      gene from DHAV (strain GX1201). Under optimal reaction conditions, the
      sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse
      transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg
      (6.59*10(4) copies) per reaction. No cross-reactivity was observed from the
      samples of other duck viruses, which is in good accordance with RT-PCR.
      Furthermore, a positive reaction can be visually inspected by observing turbidity
      or color change after the addition of SYBR green I dye. The DHAV-C-specific RT
      LAMP assay was applied to the samples and compared with RT-PCR. The positive
      sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR.
      Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and
      cost-effective method of DHAV-C detection. This assay has potential applications
      in both clinical diagnosis and field surveillance of DHAV-C infection. 

PMID- 24291149
TI  - Detection and quantitation of Agrotis baculoviruses in mixed infections.
AB  - At least four distinct baculoviruses, namely the Agrotis segetum
      nucleopolyhedrovirus A (AgseNPV-A), the A. segetum nucleopolyhedrovirus B
      (AgseNPV-B), the Agrotis ipsilon nucleopolyhedrovirus (AgipNPV) and the A.
      segetum granulovirus (AgseGV) have been isolated from larval stages (cutworms) of
      the species A. segetum and A. ipsilon (Lepidoptera: Noctuidae), which are serious
      soil pests in agriculture. Cutworms can become infected by at least one of these
      four baculoviruses and also co-infections of A. segetum larvae with AgseNPV-B and
      AgseGV are observed under laboratory conditions. Because of their adaption to
      common hosts and the occurrence in mixed infections, these viruses have a
      considerable potential as biological control agents of cutworms and are suitable
      objects to decipher the co-evolution and population dynamics of baculoviruses in
      mixed infections. However, to facilitate studies on these viruses a reliable tool
      for detection and identification is essential. A method based on highly specific
      oligonucleotide primers for multiplex polymerase chain reaction (PCR) that led to
      the amplification of discriminating fragments of the polyhedrin (polh) and
      granulin (gran) gene of AgseNPV-A, AgseNPV-B, AgipNPV and AgseGV, was
      established. Furthermore, the AgseNPV-B and AgseGV specific pairs of primers were
      applied in real-time PCR (qPCR) for AgseNPV-B/AgseGV ratio determination in
      samples of mixed infections. It is demonstrated further that for quantifying NPVs
      and GVs in mixed infections, the method of occlusion body isolation is most
      crucial and significantly influences the results. 

PMID- 24291151
TI  - Rationale and study protocol for the 'active teen leaders avoiding screen-time'
      (ATLAS) group randomized controlled trial: an obesity prevention intervention for
      adolescent boys from schools in low-income communities.
AB  - INTRODUCTION: The negative consequences of unhealthy weight gain and the high
      likelihood of pediatric obesity tracking into adulthood highlight the importance
      of targeting youth who are 'at risk' of obesity. The aim of this paper is to
      report the rationale and study protocol for the 'Active Teen Leaders Avoiding
      Screen-time' (ATLAS) obesity prevention intervention for adolescent boys living
      in low-income communities. METHODS/DESIGN: The ATLAS intervention will be
      evaluated using a cluster randomized controlled trial in 14 secondary schools in
      the state of New South Wales (NSW), Australia (2012 to 2014). ATLAS is an 8-month
      multi-component, school-based program informed by self-determination theory and
      social cognitive theory. The intervention consists of teacher professional
      development, enhanced school-sport sessions, researcher-led seminars, lunch-time
      physical activity mentoring sessions, pedometers for self-monitoring, provision
      of equipment to schools, parental newsletters, and a smartphone application and
      website. Assessments were conducted at baseline and will be completed again at 9-
      and 18-months from baseline. Primary outcomes are body mass index (BMI) and waist
      circumference. Secondary outcomes include BMI z-scores, body fat (bioelectrical
      impedance analysis), physical activity (accelerometers), muscular fitness (grip
      strength and push-ups), screen-time, sugar-sweetened beverage consumption,
      resistance training skill competency, daytime sleepiness, subjective well-being,
      physical self-perception, pathological video gaming, and aggression. Hypothesized
      mediators of behavior change will also be explored. DISCUSSION: ATLAS is an
      innovative school-based intervention designed to improve the health behaviors and
      related outcomes of adolescent males in low-income communities.

PMID- 24291150
TI  - Neuroimaging studies of factors related to exercise: rationale and design of a 9
      month trial.
AB  - The prevalence of obesity is high resulting from chronic imbalances between
      energy intake and expenditure. On the expenditure side, regular exercise is
      associated with health benefits, including enhanced brain function. The benefits
      of exercise are not immediate and require persistence to be realized. Brain
      regions associated with health-related decisions, such as whether or not to
      exercise or controlling the impulse to engage in immediately rewarding activities
      (e.g., sedentary behavior), include reward processing and cognitive control
      regions. A 9 month aerobic exercise study will be conducted in 180 sedentary
      adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI =
      29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing
      and impulse control that may affect adherence in a new exercise regimen. The
      primary aim is to use functional magnetic resonance imaging (fMRI) to examine
      reward processing and impulse control among participants that adhere (exercise
      >80% of sessions) and those that do not adhere to a nine-month exercise
      intervention with secondary analyses comparing sedentary obese and sedentary
      healthy weight participants. Our results will provide valuable information
      characterizing brain activation underlying reward processing and impulse control
      in sedentary obese and healthy weight individuals. In addition, our results may
      identify brain activation predictors of adherence and success in the exercise
      program along with measuring the effects of exercise and improved fitness on
      brain activation.

PMID- 24291152
TI  - Therapeutic time window and underlying therapeutic mechanism of breviscapine
      injection against cerebral ischemia/reperfusion injury in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Breviscapine injection is a Chinese herbal
      medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.
      Mazz. It has been widely used for treating cardiovascular and cerebrovascular
      diseases. However, the therapeutic time window and the action mechanism of
      breviscapine are still unclear. The present study was designed to investigate the
      therapeutic time window and underlying therapeutic mechanism of breviscapine
      injection against cerebral ischemic/reperfusion injury. MATERIALS AND METHODS:
      Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h
      followed by 24h of reperfusion. Experiment part 1 was used to investigate the
      therapeutic time window of breviscapine. Rats were injected intravenously with
      50mg/kg breviscapine at different time-points of reperfusion. After 24h of
      reperfusion, neurologic score, infarct volume, brain water content and serum
      level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2
      was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2
      nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant
      capacity of ischemia cortex were measured by ELISA and ferric-reducing
      antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot
      analysis were used to analyze the expression of nuclear factor erythroid 2
      related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). RESULTS: Part 1:
      breviscapine injection significantly ameliorated neurologic deficit, reduced
      infarct volume and water content, and suppressed the levels of NSE in a time
      dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE
      and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover,
      breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h
      of reperfusion. CONCLUSION: The therapeutic time window of breviscapine injection
      for cerebral ischemia/reperfusion injury seemed to be within 5h after
      reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway might be
      involved in the therapeutic mechanism of breviscapine injection.

PMID- 24291153
TI  - Quality of life tools in head and neck oncology.
AB  - OBJECTIVE: Quality of life (QoL) is now as much an assessment criterion in
      clinical trials in head and neck oncology as are survival and response rate. It
      is therefore important to be able to choose an adapted tool from the wide range
      of QoL instruments available. The present study presents an inventory of QoL
      scales validated in their French-language version, to facilitate the selection of
      appropriate tools showing good psychometric properties. MATERIALS AND METHODS:
      QoL scales cited in all 492 French and English language articles published
      between March 1st, 2006 and April 3rd, 2012, referenced on Medline and retrieved
      using the keywords "quality of life" AND "head and neck" AND "cancer", were
      inventoried and classified thematically in a search of the literature. RESULTS:
      Ninety QoL scales are presented by theme (ORL oncology, voice, swallowing and
      mastication, mucosities and xerostomia, etc.), specifying psychometric quality
      and citation level. CONCLUSION: The present report constitutes a guide to
      selecting QoL tools adapted to head and neck oncology studies.

PMID- 24291154
TI  - Retinal repair with induced pluripotent stem cells.
AB  - Retinal degeneration such as age-related macular degeneration and other inherited
      forms, such as Stargardt's disease and retinitis pigmentosa, and optic
      neuropathies including glaucoma and ischemic optic neuropathy are major causes of
      vision loss and blindness worldwide. Damage to retinal pigment epithelial cells
      and photoreceptors in the former, and to retinal ganglion cell axons in the optic
      nerve and their cell bodies in the retina in the latter diseases lead to the
      eventual death of these retinal cells, and in humans there is no endogenous
      replacement or repair. Cell replacement therapies provide 1 avenue to restore
      function in these diseases, particularly in the case of retinal repair, although
      there are considerable issues to overcome, including the differentiation and
      integration of the transplanted cells. What stem cell sources could be used for
      such therapies? One promising source is induced pluripotent stem cells (iPSCs),
      which could be drawn from an individual patient needing therapy, or generated and
      banked from select donors. We review developing research in the use of iPSCs for
      retinal cell replacement therapy. 

PMID- 24291156
TI  - Nitric oxide-activated hydrogen sulfide is essential for cadmium stress response
      in bermudagrass (Cynodon dactylon (L). Pers.).
AB  - Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous molecules,
      serving as important secondary messengers in plant response to various biotic and
      abiotic stresses. However, the interaction between NO and H2S in plant stress
      response was largely unclear. In this study, endogenous NO and H2S were evidently
      induced by cadmium stress treatment in bermudagrass, and exogenous applications
      of NO donor (sodium nitroprusside, SNP) or H2S donor (sodium hydrosulfide, NaHS)
      conferred improved cadmium stress tolerance. Additionally, SNP and NaHS
      treatments alleviated cadmium stress-triggered plant growth inhibition, cell
      damage and reactive oxygen species (ROS) burst, partly via modulating enzymatic
      and non-enzymatic antioxidants. Moreover, SNP and NaHS treatments also induced
      the productions of both NO and H2S in the presence of Cd. Interestingly, combined
      treatments with inhibitors and scavengers of NO and H2S under cadmium stress
      condition showed that NO signal could be blocked by both NO and H2S inhibitors
      and scavengers, while H2S signal was specifically blocked by H2S inhibitors and
      scavengers, indicating that NO-activated H2S was essential for cadmium stress
      response. Taken together, we assigned the protective roles of endogenous and
      exogenous NO and H2S in bermudagrass response to cadmium stress, and speculated
      that NO-activated H2S might be essential for cadmium stress response in
      bermudagrass. 

PMID- 24291157
TI  - Erythronium dens-canis L. (Liliaceae): an unusual case of change of leaf
      mottling.
AB  - Erythronium dens-canis is an early-flowering understory lily of southern Europe
      with two leaves and a single flower, although a number of plants have only one
      leaf and do not flower. The leaves are mottled with silvery flecks and brown
      patches, that gradually vanish turning to a lively green color. The nature and
      function of this striking variegation pattern were investigated in differently
      colored leaf parts following the springtime color change. Tissue organization was
      examined by light and electron microscopy; photosynthetic pigments were analyzed
      by spectrophotometry and HPLC; chlorophyll fluorescence parameters were evaluated
      by MINI-PAM. The results showed that brown patches originated in vacuolar
      anthocyanins in the subepidermal cell layer while air spaces between the upper
      epidermis and underlying chlorenchyma resulted in silvery flecks. The two leaf
      areas did not differ in photosynthetic pigments, chloroplast organization and
      photosynthetic parameters (F(v)/F(m), NPQ, rETR). Greening of brown patches due
      to anthocyanin resorption was faster in non-flowering plants than in flowering
      ones, occurring only when young fruits were developing. Anthocyanin disappearance
      did not change the structural-functional features of photosynthetic tissues. As a
      whole the results suggest that the anthocyanin pigmentation of E. dens-canis
      leaves does not affect the photosynthetic light use and has no photoprotective
      function. It is proposed that the complex leaf color pattern may act as a
      camouflage to escape herbivores, while the reflective silvery spots may have a
      role in attracting pollinators of this early-flowering species.

PMID- 24291158
TI  - Rubisco decrease is involved in chloroplast protrusion and Rubisco-containing
      body formation in soybean (Glycine max.) under salt stress.
AB  - Salt stress often induces declination of net photosynthetic rate (Pn), partially
      resulted from Rubisco degradation. The chloroplast protrusions (CPs) is one of
      the pathways of Rubisco exclusion from chloroplasts. To explore the relationship
      between the Rubisco contents and CPs under salt stress, Pn, maximum photochemical
      efficiency of PSII (F(v)/F(m)), carboxylation efficiency (CE) and concentration
      of Rubisco, number of CPs and Rubisco-containing Body (RCBs) were investigated
      with two differently salt-responding varieties in this experiment. We observed
      that 150 mM salt treatment resulted in not only significant decrease in Pn, CE
      and Rubisco content, but also obvious increase in the number of CPs and RCBs in
      salt-sensitive variety. Under salt stress formation of CPs resulted in production
      of much more RCBs, which could immigrate into and combine with vacuole. It may be
      a kind of important mechanism for rapid degradation of Rubisco under salt stress.
      Our conclusion provides a new sight for how Rubisco can be fast degraded under
      salt stress.

PMID- 24291155
TI  - Extracellular matrix as an inductive scaffold for functional tissue
      reconstruction.
AB  - The extracellular matrix (ECM) is a meshwork of both structural and functional
      proteins assembled in unique tissue-specific architectures. The ECM both provides
      the mechanical framework for each tissue and organ and is a substrate for cell
      signaling. The ECM is highly dynamic, and cells both receive signals from the ECM
      and contribute to its content and organization. This process of "dynamic
      reciprocity" is key to tissue development and for homeostasis. Based upon these
      important functions, ECM-based materials have been used in a wide variety of
      tissue engineering and regenerative medicine approaches to tissue reconstruction.
      It has been demonstrated that ECM-based materials, when appropriately prepared,
      can act as inductive templates for constructive remodeling. Specifically, such
      materials act as templates for the induction of de novo functional, site
      appropriate, tissue formation. Herein, the diverse structural and functional
      roles of the ECM are reviewed to provide a rationale for the use of ECM scaffolds
      in regenerative medicine. Translational examples of ECM scaffolds in regenerative
      are provided, and the potential mechanisms by which ECM scaffolds elicit
      constructive remodeling are discussed. A better understanding of the ability of
      ECM scaffold materials to define the microenvironment of the injury site will
      lead to improved clinical outcomes associated with their use.

PMID- 24291159
TI  - Oligomeric proanthocyanidins alleviate hexabromocyclododecane-induced
      cytotoxicity in HepG2 cells through regulation on ROS formation and mitochondrial
      pathway.
AB  - Hexabromocyclododecane (HBCD), a type of brominated flame retardants (BFR), has
      become ubiquitous organic contaminants in recent years. However, studies on HBCD
      toxicity and the related molecular mechanisms are so far limited. The objective
      of the present study was to investigate the effects of oligomeric
      proanthocyanidins (OPCs) on cytotoxicity induced by HBCD and the underlying
      molecular mechanisms. HepG2 cells were treated with HBCD and/or OPCs at different
      concentrations, and cell viability, cell apoptosis, reactive oxygen species (ROS)
      production, cellular Ca(2+) level, mitochondrial membrane potential (DeltaPsi),
      cytochrome C (Cyt-c) release, and nuclear factor-erythroid 2-related factor 2
      (Nrf2) proteins expression were evaluated. Results showed that HBCD induced toxic
      effects in HepG2 cells in a concentration-dependent manner. HBCD at high
      concentrations (40 and 60MUM) caused a significant decrease of cell viability and
      led to elevated cell apoptosis ratio, intracellular Ca(2+) level, cytoplasmic Cyt
      c level, and ROS production, together with a loss of DeltaPsi and mobilization of
      Nrf2. Pretreatment with OPCs effectively attenuated the cytotoxic effects and ROS
      production, as well as mitochondrial responses induced by HBCD. Thus, OPCs could
      alleviate cytotoxicity in HepG2 cells induced by HBCD through regulation on
      intracellular Ca(2+) level and ROS formation in a mitochondrial pathway.

PMID- 24291160
TI  - 2-Methoxy-1,4-Naphthoquinone (MNQ) suppresses the invasion and migration of a
      human metastatic breast cancer cell line (MDA-MB-231).
AB  - Metastasis contributes to the escalating mortality rate among cancer patients
      worldwide. The search for novel and more effective anti-metastatic agent is
      crucial owing to the lack of anticancer drugs that can successfully combat
      metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4
      Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion
      assays, the number of cells permeating across a Matrigel barrier was found to be
      decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 MUM). In
      wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell
      migration in which significant reduction in the zone of closure was observed as
      compared to untreated controls. Furthermore, the proteolytic activity of a
      pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also
      downregulated by MNQ as determined by gelatin zymography. This study reports for
      the first time, the ability of MNQ to inhibit the invasion and migration
      characteristics of a highly metastatic MDA-MB-231 cancer cell line.

PMID- 24291161
TI  - Evaluation of cytotoxicity, genotoxicity and embryotoxicity of insecticide
      propoxur using flounder gill (FG) cells and zebrafish embryos.
AB  - Cytotoxicity, genotoxicity and embryotoxicity of carbamate insecticide propoxur
      were evaluated using flounder gill (FG) cells and zebrafish embryos. The
      cytotoxicity of propoxur in FG cells was analyzed by MTT, neutral red uptake
      (NRU), lactate dehydrogenase (LDH) release and Hoechst 33342 and propidium iodide
      double staining, and acute cytotoxic effects were observed in a concentration
      dependent manner. The 24h-IC50 values of 89.96 +/- 1.04, 103.4 +/- 1.14 and 86.59
      +/- 1.13 MUg/ml propoxur were obtained by MTT, NRU and LDH assays, respectively.
      The lethal effects were induced in FG cells mainly through necrosis but not
      apoptosis as evidenced by double fluorescence staining. Comet assay showed weak
      genotoxic effects and statistically significant DNA damages were recorded in the
      cells exposed to highest tested concentration of 75 MUg/ml propoxur (p<0.05).
      Propoxur exerted obvious acute toxic effects on the survival, spontaneous
      movement, hatching and heart rate, and development (yolk and pericardial sac
      edema) of zebrafish embryos in both time- and concentration-dependent manner only
      at ? 100 MUg/ml. The corresponding 24h-, 48 h- and 96 h-LC50 values of propoxur
      in zebrafish embryos were 166.4 +/- 1.06, 146.3 +/- 1.07 and 134.8 +/- 1.06
      MUg/ml, respectively. The above data obtained suggest a low acute toxicity of
      propoxur to the in vitro cultured FG cells and zebrafish embryos.

PMID- 24291162
TI  - Cadmium (Cd(2+)) exposure differentially elicits both cell proliferation and cell
      death related responses in SK-RC-45.
AB  - Cadmium (Cd(2+)) is a major nephrotoxic environmental pollutant, affecting mostly
      proximal convoluted tubule (PCT) cells of the mammalian kidney, while
      conditionally Cd(2+) could also elicit protective responses with great variety
      and variability in different systems. The present study was designed to evaluate
      the molecular mechanism of Cd(2+) toxicity on human PCT derived Renal Cell
      Carcinoma (RCC), SK-RC-45 and compare its responses with normal human PCT derived
      cell line, NKE. Exposure of SK-RC-45 cells with different concentrations of CdCl2
      (e.g. 0, 10 and 20MUM) in serum free medium for 24h generate considerable amount
      of ROS, accompanied with decreased cell viability and alternations in the
      cellular and nuclear morphologies, heat shock responses and GCLC mediated
      protective responses. Also phosphatidylserine externalization, augmentation in
      the level of caspase-3, PARP, BAD, Apaf1 and cleaved caspase-9 along with
      decreased expression of Bcl2 and release of cytochrome c confirmed that, Cd(2+)
      dose dependently induces solely intrinsic pathway of apoptosis in SK-RC-45,
      independent of JNK. Furthermore, the non-toxic concentration (10MUM) of Cd(2+)
      induced nuclear translocation of Nrf2 and increased expression in the level of HO
      1 enzyme suggesting that at the milder concentration, Cd(2+) induces protective
      signaling pathways. On the other hand, exposure of NKE to different
      concentrations of CdCl2 (e.g. 0, 10, 20, 30 and 50MUM) under the same conditions
      elevate stronger heat shock and SOD2 mediated protective responses. In contrary
      to the RCC PCT, the normal PCT derived cell follows JNK dependent and extrinsic
      pathways of apoptosis. Cumulatively, these results suggest that Cd(2+) exposure
      dose dependently elicit both cell proliferative and cell death related responses
      in SK-RC-45 cells and is differentially regulated with respect to normal kidney
      epithelia derived NKE cells.

PMID- 24291163
TI  - Extraction of total nucleic acid based on silica-coated magnetic particles for RT
      qPCR detection of plant RNA virus/viroid.
AB  - In this study, a nucleic acid extraction method based on silica-coated magnetic
      particles (SMPs) and RT-qPCR assay was developed to detect Arabis mosaic virus
      (ArMV), Lily symptomless virus (LSV), Hop stunt viroid (HSVd) and grape yellow
      speckle viroid 1 (GYSVd-1). The amplification sequences of RT-qPCR were reversely
      transcribed in vitro as RNA standard templates. The standard curves covered six
      or seven orders of magnitude with a detection limit of 100 copies per each assay.
      Extraction efficiency of the SMPs method was evaluated by recovering spiked
      ssRNAs from plant samples and compared to two commercial kits (TRIzol and RNeasy
      Plant mini kit). Results showed that the recovery rate of SMPs method was
      comparable to the commercial kits when spiked ssRNAs were extracted from lily
      leaves, whereas it was two or three times higher than commercial kits when spiked
      ssRNAs were extracted from grapevine leaves. SMPs method was also used to extract
      viral nucleic acid from15 ArMV-positive lily leaf samples and 15 LSV-positive
      lily leaf samples. SMPs method did not show statistically significant difference
      from other methods on detecting ArMV, but LSV. The SMPs method has the same level
      of virus load as the TRIzol, and its mean virus load of was 0.5log10 lower than
      the RNeasy Plant mini kit. Nucleic acid was extracted from 19 grapevine-leaf
      samples with SMPs and the two commercial kits and subsequently screened for HSVd
      and GYSVd-1 by RT-qPCR. Regardless of HSVd or GYSVd-1, SMPs method outperforms
      other methods on both positive rate and the viroid load. In conclusion, SMPs
      method was able to efficiently extract the nucleic acid of RNA viruses or
      viroids, especially grapevine viroids, from lily-leaf or grapevine-leaf samples
      for RT-qPCR detection. 

PMID- 24291164
TI  - Editorial comment.

PMID- 24291165
TI  - Editorial comment.

PMID- 24291166
TI  - Molecular characterization and expression profiles of olfactory receptor genes in
      the parasitic wasp, Microplitis mediator (Hymenoptera: Braconidae).
AB  - Olfactory receptors (OR) are believed to fulfil an indispensable role in insects
      host-seeking, mating and ovipositing. We obtained 4785 high-quality expressed
      sequencing tags (EST) from the antennal cDNA library of the parasitic wasp
      Microplitis mediator, a natural enemy of crop pests. After assembling, 786
      contigs and 2130 singletons were generated. Using BLAST searches, a number of
      olfactory-related genes were identified, including ESTs encoding for 25 ORs. 14
      full-length OR genes were cloned and their expression profiles in the wasp
      olfactory organs were quantified by real-time qRT-PCR. The results indicated a
      diverse distribution between the tissues and genders, yet the majority of OR
      genes are highly expressed in antennae. Three OR genes (Or2, Or12 and Or13) are
      highly expressed in female antennae, eight OR genes (ORco, Or3, Or4, Or5, Or7,
      Or8, Or9 and Or11) are highly expressed in male antennae. This is the first
      report on tissue-specific expression of wasp OR genes. Our study provides a
      foundational knowledge to explore and understand the molecular basis of odorant
      reception in this parasitic wasp and for the study of trophic interactions of
      natural enemy. 

PMID- 24291167
TI  - Moving beyond a heat-labile enterotoxin-based vaccine against enterotoxigenic
      Escherichia coli.

PMID- 24291168
TI  - Efficacy and safety of a patch vaccine containing heat-labile toxin from
      Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double
      blind, placebo-controlled field trial in travellers from Europe to Mexico and
      Guatemala.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major cause of
      travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch
      vaccine containing the pathogen's heat-labile toxin (LT) in a population of
      travellers to Mexico and Guatemala. METHODS: In this phase 3, randomised, double
      blind, placebo-controlled field trial, healthy adults (aged 18-64 years)
      travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1
      ratio by a dynamic electronic randomisation system to receive transcutaneous
      immunisation with a patch containing 37.5 MUg of ETEC LT or a placebo patch.
      Participants, site staff, and the investigators who did the analyses were masked
      to group assignment. Participants were vaccinated before travel, with two patches
      given 14 days apart. In the destination country, participants tracked stool
      output in a diary and provided stool samples for pathogen identification if
      diarrhoea occurred. The primary endpoint was the proportion of participants with
      at least one episode of moderate-to-severe diarrhoea (defined as four or more
      unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT
      and heat-stable toxin [ST]) were detected. The study is registered at
      ClinicalTrials.gov, number NCT00993681. FINDINGS: 2036 participants were
      recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016
      allocated to receive the LT patch and 1020 the placebo patch. 821 participants in
      the LT-patch group and 823 in the placebo group received both vaccinations and
      were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2)
      participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group
      had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9;
      p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash,
      pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943
      (93%) of 1015 participants in the LT-patch group, compared with 1444 local
      adverse events in 574 (56%) of 1019 participants in the placebo group (p<0.0001).
      Serious adverse events occurred in 25 participants (14 in the LT-patch group and
      11 in the placebo group), with all regarded as either unrelated or possibly
      related to treatment. Vaccine-induced hyperpigmentation persisted for at least
      180 days after vaccination in 150 (18%) of the 849 participants who received both
      vaccinations and returned for final assessment in the LT-patch group, compared
      with none of the 842 participants in the placebo group. The vaccine was
      immunogenic, with a post-vaccination geometric mean titre of LT-specific serum
      immunoglobulin G of 3400.29, compared with 315.41 in the placebo group.
      INTERPRETATION: Although the LT antigen was delivered effectively by the skin
      patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or
      other organisms. Future vaccines against travellers' diarrhoea might need to
      include several antigens against various diarrhoeal pathogens, and might need to
      be able to generate mucosal and higher systemic immunity.

PMID- 24291169
TI  - Anatomical characterisation of the cricothyroid membrane in females of
      childbearing age using computed tomography.
AB  - BACKGROUND: In the event of failure to secure the airway by conventional means,
      it may be necessary to perform invasive airway access via the cricothyroid
      membrane. No studies have addressed anatomy of this structure in the obstetric
      population. We aimed to review the anatomical variation of this structure in a
      population of childbearing age. METHODS: We searched the radiology database for
      computed tomography studies of the neck performed in a 13-month period in
      consecutive patients aged 15-55 years. Studies on 18 females and 22 males were
      reviewed. Male patients were included for comparison. Data were reconstructed
      using a high spatial frequency algorithm to optimise spatial resolution. Five
      parameters were measured: distance from the skin to the membrane, maximum midline
      height of the membrane in the vertical plane, maximum transverse diameter of the
      membrane, neck diameter and cartilaginous calcification. RESULTS: The distance
      (mean range) from skin to the membrane was similar in females and males (16.2 [3
      33] vs. 13.9 [3-37] mm, P = 0.42). The vertical height (9.9 [7-17] vs. 11.4 [8
      15] mm, P = 0.04) and maximum width of the membrane (14.5 [10-17] mm vs. 12.5 [10
      15] mm, P < 0.01) were greater in males. Cartilaginous calcification was low and
      did not differ between genders. CONCLUSIONS: The cricothyroid membrane is not
      necessarily a superficial structure and consequently may be difficult to palpate.
      The smallest dimensions of the membrane indicate that smaller than recommended
      cricothyroidotomy devices may be required in some patients as the external
      diameter of commercial trocar devices and tracheal tubes may exceed 7 mm.

PMID- 24291170
TI  - Octreotide modulates the effects on fibrosis of TNF-alpha, TGF-beta and PDGF in
      activated rat hepatic stellate cells.
AB  - BACKGROUND AND AIMS: Somatostatin and its analogs may influence hepatic fibrosis
      interfering through several mechanisms. The aim of this study was to investigate
      the effect of octreotide on cytokine activated hepatic stellate cells (HSC).
      METHODS: Primary HSCs were isolated from rats and were cultured on plastic for
      activation. Expression of somatostatin receptors (SSTR) was investigated in
      cultured HSCs by immunofluorescence and western blot. The effect of octreotide on
      cellular proliferation was studied with the MTT assay and western blot for alpha1
      procollagen (alpha1-PROC) production in TNFalpha, TGF-beta1 or PDGF treated HSCs.
      Phosphotyrosine (PTP) and phosphoserine-phosphothreonine (STP) phosphatases
      inhibition was performed with sodium orthovanadate and okadaic acid respectively.
      RESULTS: Activated HSC express SSTR subtypes 1, 2A, 2B, 3 and 4 and their
      expression is enhanced by further HSC activation. Octreotide did not have an
      effect on HSC proliferation but inhibited plastic induced alpha1-PROC production.
      Interestingly, it enhanced PDGF-induced HSC proliferation but inhibited PDGF and
      TGFbeta1 dependent expression of alpha1-PROC, while an opposite effect was
      observed in TNFalpha-induced cell proliferation and collagen production. PTP
      inhibition reversed the inhibitory effect of octreotide on alpha1-PROC, but
      potentiated its effect on PDGF and TGFbeta1 dependent alpha1-PROC production.
      Finally, STP inhibition profoundly inhibited alpha1-PROC expression in all cases
      suggesting that both STP and PTP phosphatases are important regulators of pro
      fibrotic mechanisms. CONCLUSIONS: The net effect of octreotide on HSCs and
      therefore liver fibrosis is subject to the cytokine microenvironment of these
      cells. This effect is modulated by PTPs and STPs inhibition. Especially in the
      case of STPs their profibrotic effects could be an interesting new therapeutic
      target in liver fibrosis.

PMID- 24291171
TI  - Nuclear aggregates of polyamines in a radiation-induced DNA damage model.
AB  - Polyamines (PA) are believed to protect DNA minimizing the effect of radiation
      damage either by inducing DNA compaction and aggregation or acting as scavengers
      of free radicals. Using an in vitro pDNA double strand breakage assay based on
      gel electrophoretic mobility, we compared the protective capability of PA against
      gamma-radiation with that of compounds generated by the supramolecular self
      assembly of nuclear polyamines and phosphates, named Nuclear Aggregates of
      Polyamines (NAPs). Both unassembled PA and in vitro produced NAPs (ivNAPs) were
      ineffective in conferring pDNA protection at the sub-mM concentration. Single PA
      showed an appreciable protective effect only at high (mM) concentrations.
      However, concentrations of spermine (4+) within a critical range (0.481 mM)
      induced pDNA precipitation, an event that was not observed with NAPs-pDNA
      interaction. We conclude that the interaction of individual PA is ineffective to
      assure DNA protection, simultaneously preserving the flexibility and charge
      density of the double strand. Furthermore, data obtained by testing polyamine and
      ivNAPS with the current radiation-induced DNA damage model support the concept
      that PA-phosphate aggregates are the only forms through which PA interact with
      DNA.

PMID- 24291172
TI  - Inhibition of 5-lipoxygenase as anti-inflammatory mode of action of Plectranthus
      zeylanicus Benth and chemical characterization of ingredients by a mass
      spectrometric approach.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The perennial herb Plectranthus zeylanicus Benth
      is extensively used in traditional medicine in Sri Lanka and South India for
      treating inflammatory conditions, but pharmacological features of Plectranthus
      zeylanicus are hardly explored in order to understand and rationalize its use in
      ethnomedicine. As 5-lipoxygenase (5-LO) is a key enzyme in inflammatory disorders
      such as asthma or atherosclerosis, we investigated 5-LO inhibition by
      Plectranthus zeylanicus extracts and analyzed relevant constituents. MATERIALS
      AND METHODS: We applied cell-free and cell-based assays to investigate
      suppression of 5-LO activity. Cell viability, radical scavenger activities, and
      inhibition of reactive oxygen species formation (ROS) in neutrophils were
      analysed to exclude unspecific cytotoxic or antioxidant effects. Constituents of
      the extracts were characterized by bioassay-guided fractionation and by analysis
      using gas or liquid chromatography coupled to mass spectrometric (Orbitrap)
      analysis. RESULTS: Extracts of Plectranthus zeylanicus prepared with n-hexane or
      dichloromethane potently suppressed 5-LO activity in stimulated human neutrophils
      (IC50=6.6 and 12ug/ml, respectively) and inhibited isolated human recombinant 5
      LO (IC50=0.7 and 1.2ug/ml, respectively). In contrast, no significant radical
      scavenging activity or suppression of ROS formation was observed, and neutrophil
      viability was unaffected. Besides ubiquitously occurring ingredients, coleone P,
      cinncassiol A and C, and callistric acid were identified as constituents in the
      most active fraction. CONCLUSIONS: Together, potent inhibition of 5-LO activity,
      without concomitant anti-oxidant activity and cytotoxic effects, rationalizes the
      ethnopharmacological use of Plectranthus zeylanicus as anti-inflammatory remedy.
      Modern chromatographic/mass spectrometric analysis reveals discrete chemical
      structures of relevant constituents.

PMID- 24291173
TI  - Olmesartan protects against oxidative stress possibly through the Nrf2 signaling
      pathway and inhibits inflammation in daunorubicin-induced nephrotoxicity in rats.
AB  - Anthracycline anticancer drug daunorubicin (DNR) can induce chronic
      nephrotoxicity, which is believed to be based on oxidative injury. Olmesartan has
      significant blood pressure lowering effect via modulating renin-angiotensin
      system although its mechanism of action in DNR-induced renal injury is largely
      unknown. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2)
      is an important regulator of cellular oxidative stress. This study examined the
      role of Nrf2 in olmesartan-mediated antioxidant effects in DNR induced kidney
      cells. In addition, key factors involved in promoting inflammation and oxidative
      stress were studied. Sprague-Dawley rats were treated with a cumulative dose of 9
      mg/kg DNR (i.v.). Olmesartan was administered orally every day for 6 weeks. DNR
      treated rats showed nephrotoxicity as evidenced by worsening renal function,
      which was evaluated by measuring total cholesterol, triglyceride levels in kidney
      tissue and histopathological approaches; treatment with olmesartan reversed these
      changes. Furthermore, olmesartan treatment down-regulated phospho-MAPKAPK-2,
      caspase-12, p47(phox), p67(phox), upregulated renal expression of PPAR-gamma, Bcl
      xL, glutathione peroxidase and Nrf2. Furthermore, olmesartan down-regulated
      matrix metalloproteinase-2 and angiotensin II type I receptor expression in the
      kidney. In conclusion, the result demonstrated that angiotensin II and oxidative
      stress play a key role in DNR-induced nephrotoxicity. The present results
      indicated that olmesartan protects against oxidative stress, which may be
      possibly via the induction of Nrf2 signaling pathways.

PMID- 24291174
TI  - Molecular characterization and evolutionary analysis of horse BAFF-R, a tumor
      necrosis factor receptor related to B-cell survival.
AB  - B-cell survival depends on signals induced by B-cell activating factor (BAFF)
      that binds to the BAFF receptor (BAFF-R). Herein, a BAFF-R homolog was identified
      in a horse (Equus caballus). The horse BAFF-R gene, located on chromosome 28,
      spans 1444 base pairs and encodes a 183-amino acid protein. The protein is
      structurally conserved, in which the DxL motif plays an important role in binding
      to BAFF. Furthermore, the horse BAFF-R extracellular domain was expressed and
      purified, which specifically bound to His6-sBAFF and had the capability of
      blocking the function of His6-sBAFF in vitro. Finally, evolutionary analyses
      indicated that some codon sites of BAFF-R evolve with positive selection and that
      the genetic relationship among a horse, Chiroptera, and Caniformia are the
      closest. 

PMID- 24291175
TI  - Roles of microsomal prostaglandin E synthase-1 in lung metastasis formation in
      prostate cancer RM9 cells.
AB  - Cyclooxygenase-2 (COX-2) is known to correlate with a poor prognosis of prostate
      cancer and contribute to tumor metastasis. However, the precise mechanism of this
      phenomenon remains unknown. We have previously reported that host stromal
      microsomal prostaglandin E synthase-1 (mPGES-1) appeared critical for tumor
      associated angiogenesis and tumor growth. Here, we tested whether or not mPGES-1
      has a critical role in lung metastasis formation of prostate cancer. Murine
      prostate cancer cells (RM9) were intravenously injected and lung metastasis was
      estimated by counting colonies in the lungs. Mice treated with a selective COX-2
      inhibitor, celocoxib, were suppressed lung metastasis compared to vehicle mice.
      This lung metastasis formation was also reduced in mPGES-1 knockout (mPGES-1 KO)
      mice, compared with wild type (WT) mice. This was accompanied with reduced
      angiogenesis around the metastasized colonies of RM9. Plasma protein levels and
      metastasized lung tissue mRNA levels of vascular endothelial growth factor (VEGF)
      and stromal cell derived factor-1 (SDF-1) were significantly suppressed in mPGES
      1 KO mice in comparison with WT mice. In addition, the expressions of matrix
      metalloproteinases (MMP)-9, and metalloproteinases (MMP)-2 were down-regulated in
      metastatic lungs in mPGES-1 KO mice. These results suggested that host mPGES-1
      was essential for MMP-2 and MMP-9 up-regulation that enhances tumor metastasis.
      mPGES-1 appears to be critical for tumor metastasis in prostate cancers. mPGES-1
      inhibitors may be useful to protect against prostate cancer metastasis. 

PMID- 24291177
TI  - Comparative evaluation of eleven commercial DNA extraction kits for real-time PCR
      detection of Bacillus anthracis spores in spiked dairy samples.
AB  - Spores of Bacillus anthracis are highly resistant and can survive conditions used
      for food preservation. Sample size and complexity represent the major hurdles for
      pathogen detection in food-related settings. Eleven commercial DNA extraction
      kits were evaluated for detection of B. anthracis spores by quantitative real
      time PCR (qPCR) in dairy products. DNA was extracted from serial dilutions of B.
      anthracis spores in milk powder, cream cheese, whole milk and buttermilk. Three
      kits (QIAamp DNA mini kit, Invisorb Food kit I and II) were determined to produce
      the lowest limit of detections (LODs) with equally good performance. These kits
      employed lysozyme and proteinase K treatments or proteinase K in combination with
      cethyltrimethylamonium bromide-mediated (CTAB) precipitation of cell debris for
      cell disruption and DNA release. The LODs for these three kits were determined as
      10(2) spores/ml of distilled water, 10(3)s pores/20 mg of powdered milk and 10(4)
      spores/100 mg of cream cheese, respectively. Performance testing of the QIAamp
      DNA mini kit demonstrated a good reproducibility and appropriate detection limits
      from 10(3)/ml for butter milk, 10(4)/ml for whole milk and 10(4)/100 mg for low
      fat cream cheese. However, DNA extraction efficiency was strongly inhibited by
      cream cheese with higher fat contents with an increased LOD of 10(6)/100 mg
      spores. This study demonstrated that qPCR detection depends directly on the
      appropriate DNA extraction method for an individual food matrix and bacterial
      agent.

PMID- 24291176
TI  - Efficacy of the combined application of chitosan and Locust Bean Gum with
      different citrus essential oils to control postharvest spoilage caused by
      Aspergillus flavus in dates.
AB  - This study reports the efficacy of the combined application of chitosan (CH) and
      Locust Bean Gum (LBG) in combination with different citrus essential oils (EOs)
      to inhibit Aspergillus flavus in vitro and on artificially infected dates for a
      storage period of 12 days. The effect of these treatments on the fruits' sensory
      characteristics was evaluated to verify the complete absence of off-odours and
      off-flavours. Bergamot EO was the most effective in reducing mycelial growth,
      followed by bitter orange EO. Both bergamot and bitter orange oils significantly
      reduced conidial germination and a complete inhibition was obtained at
      concentrations higher than 2%. The mixtures based on CH-2% (v/v) bergamot EO or
      CH-2% (v/v) bitter orange EO proved to be the most effective coatings to reduce
      conidial germination resulting in an 87-90% inhibition compared with the control.
      In fruit decay assays coatings based on CH incorporating citrus oils were able to
      reduce fungal decay in the range of 52-62% at day 12. The study results and the
      complete absence of off-flavours and off-odours demonstrate the potential of CH
      coatings carrying citrus EOs at sub-inhibitory concentrations to control
      postharvest growth of A. flavus in dates.

PMID- 24291178
TI  - Microbial diversity and dynamics during the production of May bryndza cheese.
AB  - Diversity and dynamics of microbial cultures were studied during the production
      of May bryndza cheese, a traditional Slovak cheese produced from unpasteurized
      ewes' milk. Quantitative culture-based data were obtained for lactobacilli,
      lactococci, total mesophilic aerobic counts, coliforms, E. coli, staphylococci,
      coagulase-positive staphylococci, yeasts, fungi and Geotrichum spp. in ewes'
      milk, curd produced from it and ripened for 0 - 10 days, and in bryndza cheese
      produced from the curd, in three consecutive batches. Diversity of prokaryotes
      and eukaryotes in selected stages of the production was studied by non-culture
      approach based on amplification of 16S rDNA and internal transcribed spacer
      region, coupled to denaturing gradient gel electrophoresis and sequencing. The
      culture-based data demonstrated an overall trend of growth of the microbial
      population contributing to lactic acid production and to ripening of the cheese,
      lactobacilli, lactococci and Geotrichum spp. growing up to densities of 10(8)
      CFU/g, 10(9) CFU/g and 10(5) CFU/g, respectively, in all three consecutive
      batches of bryndza cheese. The diversity of bacteria encompassed Acinetobacter
      calcoaceticus, Acinetobacter guillouiae, Acinetobacter sp., Acinetobacter
      johnsonii, Citrobacter braakii, Clostridium bartlettii, Corynebacterium callunae,
      Corynebacterium maris, Enterobacter aerogenes, Enterobacter asburiae,
      Enterobacter hormaechei, Enterococcus faecium, Enterococcus pallens, Escherichia
      coli, Haemophilus haemolyticus, Hafnia alvei, Kluyvera cryocrescens,
      Lactobacillus helveticus, Lactococcus garvieae, Lc. lactis subsp. cremoris, Lc.
      lactis subsp. lactis, "Leuconostoc garlicum", Mannheimia glucosida, Mannheimia
      haemolytica, Pseudomonas sp., Ps. fluorescens, "Ps. reactans", Raoultella
      ornithinolytica, R. terrigena, "Rothia arfidiae", Staphylococcus aureus, Staph.
      epidermidis, Staph. felis, Staph. pasteuri, Staph. sciuri, Staph. xylosus,
      Streptococcus parauberis, Str. thermophilus and Variovorax paradoxus. The
      diversity of yeasts and fungi encompassed Alternaria alternata, "Ascomycete sp.",
      Aspergillus fumigatus, Beauveria brongniartii, Candida xylopsoci, C. inconspicua,
      Cladosporium cladosporioides, Debaromyces hansenii, Fomes fomentarius,
      Galactomyces candidus, Gymnoascus reesii, Chaetomium globosum, Kluyveromyces
      marxianus, Metarhizium anisopliae, Penicillium aurantiogriseum, P. camemberti, P.
      freii, P. polonicum, P. viridicatum, Pichia kudriavzevii, Sordaria alcina,
      Trichosporon lactis and Yarrowia lipolytica.

PMID- 24291179
TI  - Microbial quality of frozen Nile crocodile (Crocodylus niloticus) meat samples
      from three selected farms in Zimbabwe.
AB  - Microbial quality of frozen Nile crocodile (Crocodylus niloticus) meat from three
      farms in Zimbabwe was assessed based on 2051 samples collected for pre-export
      testing during 2006 to 2011. Data were perused by season and year in terms of
      aerobic plate (APC), coliform (CC), Escherichia coli (ECC) and Listeria
      monocytogenes (LMC) counts and the presence of Salmonella spp. The log10
      transformed data were compared among the farms and seasons using the Kruskal
      Wallis test. Microbial quality of the samples was graded based on the EC No.
      2073.2005 criteria for beef. The mean APC and CC for the crocodile meat differed
      significantly (P=0.000) among the farms with the highest APC (3.2+/-0.05 log10
      cfu/g) and the lowest (2.7+/-0.05 log10 cfu/g) recorded from farms A and C,
      respectively. There were no significant differences (P>0.05) in ECC and LMC among
      the farms, while Salmonella spp. were only isolated from one farm. Although the
      microbial quality of frozen crocodile meat from these farms was generally within
      acceptable limits, the isolation of E. coli and Salmonella spp. is of public
      health concern. Thus, implementing of measures to control the pasteurizing
      process and to minimize bacterial contamination of crocodile meat after
      pasteurization need to be carefully considered.

PMID- 24291180
TI  - Detection of viable Escherichia coli O157:H7 in ground beef by propidium
      monoazide real-time PCR.
AB  - Escherichia coli O157:H7 associated with food has caused many serious public
      health problems in recent years. However, only viable cells of this pathogen can
      cause infections, and false-positive detection caused by dead cells can lead to
      unnecessary product recalls. The objective of this study was to develop and
      optimize a method that combines propidium monoazide (PMA) staining with real-time
      PCR to detect only viable cells of E. coli O157:H7 in ground beef. PMA is a DNA
      intercalating dye that can penetrate compromised membranes of dead cells and bind
      to cellular DNA, preventing its amplification via a subsequent PCR. Three strains
      of E. coli O157:H7 (505B, G5310 and C7927) at concentrations of 10(0) to
      10(8)CFU/mL were used as live cells. Dead cells were obtained by heating cell
      suspensions at 85 degrees C for 15 min. Suspensions were treated with PMA and the
      optimized assay was applied to artificially contaminated ground beef with two
      different fat contents (10% and 27%). DNA was extracted and amplified by
      TaqMan(r) real-time PCR assay targeting the uidA gene for detection of E. coli
      O157:H7. Plasmid pUC19 was added as an internal amplification control (IAC). A
      treatment of 25 MUM PMA with a 10-min light exposure on ice was sufficient to
      eliminate DNA from 10(8) dead E. coli O157:H7 cells/mL. The optimized assay could
      detect as low as 10(2) CFU/mL viable E. coli O157:H7 in pure culture and 10(5)
      CFU/g in ground beef, in the presence of 10(6)/mL or g of dead cells. With an 8-h
      enrichment, 1 CFU/g viable E. coli O157:H7 in ground beef was detectable without
      interference from 10(6) dead cells/g. In conclusion, the PMA real-time PCR could
      effectively detect viable E. coli O157:H7 without being compromised by dead
      cells.

PMID- 24291181
TI  - The effects of different yeast extracts on secondary metabolite production in
      Fusarium.
AB  - Yeast extract is an important constituent in several media used for metabolite
      profiling of filamentous fungi. The nutrient composition can vary between brands
      and thereby influence production of secondary metabolites, which can be regulated
      in response to nitrogen, carbon and pH. In the present study we examined the
      production of known secondary metabolites in Fusarium pseudograminearum, Fusarium
      graminearum, Fusarium avenaceum and Fusarium fujikuroi and in each species we
      identified several secondary metabolites which are influenced by yeast extract
      brands. Deoxynivalenol and zearalenone were produced in high levels on some yeast
      extract by F. pseudograminearum and F. graminearum, while absent on others.
      Chlamydosporol, 2-AOD-3-ol and enniatins were influenced by yeast extracts in F.
      avenaceum, while bikaverin, gibberellic acid, fumonisin and fusaric acid were
      affected in F. fujikuroi. Aurofusarin and fusarin C on the other hand were not
      affected by yeast extracts in all producing strains. The observed differences in
      production in metabolite profiles show the need to use the same yeast extract
      brand in repeating experiments. The study illustrates furthermore that it can be
      beneficial to use more than one yeast extract in metabolite profiling a species. 

PMID- 24291182
TI  - An improved process of isomaltooligosaccharide production in kimchi involving the
      addition of a Leuconostoc starter and sugars.
AB  - Isomaltooligosaccharides (IMOs) are alpha-(1->6)-linked oligodextrans that show a
      prebiotic effect on Bifidobacterium spp. This study sought to improve IMO
      synthesis during lactate fermentation in kimchi by inoculating the kimchi
      fermentation mix with a starter and sugars; the psychrotrophic Leuconostoc
      citreum KACC 91035 strain with high dextransucrase activity was used as a starter
      and sucrose (58 mM) and maltose (56 mM) were added as the donor and acceptor for
      the glucose-transferring reaction of the dextransucrase, respectively. With the
      addition of both the starter and the sugars and incubation at 10 degrees C, IMOs
      were produced in kimchi after 3d. Without the starter, the IMO production rate
      and maximal concentration in kimchi were 15.05 mM/d and 75.27 mM, respectively,
      whereas with the starter, the rate and concentration increased to 22.04 mM/d and
      110.19 mM, respectively. In addition, the sucrose-maltose mix gave an appropriate
      level of sweetness by releasing fructose and prevented unfavorable polymer
      synthesis by IMO production. This result suggests that lactic acid bacteria
      expressing a highly active glycosyltransferase can be used for the synthesis of
      beneficial oligosaccharides in various fermented foods.

PMID- 24291183
TI  - Incidence of virulence factors in enterococci from raw and fermented meat and
      biofilm forming capacity at 25 degrees C and 37 degrees C.
AB  - Twenty-nine Enterococcus strains from raw and fermented meat products were
      screened for the presence of virulence genes, including those for aggregation
      substances (asa1 and asa373), cytolysin activator (cylA), collagen binding
      protein (ace), endocarditis antigen (efaA), enterococcal surface protein (esp)
      and gelatinase (gelE). Virulence gene occurrence, expression of gelatinase and
      pheromone aggregation was greater in Enterococcus faecalis than in Enterococcus
      faecium strains. All E. faecalis and 54% of E. faecium were positive for at least
      one or more virulence gene. The only strain of Enterococcus gallinarum tested
      also contained virulence genes. The effect of different growth temperatures (25
      and 37 degrees C) on biofilm formation using polystyrene plates was also
      assessed. Strong biofilm formation occurred at lower than optimum temperature in
      all three species of enterococci. Neither esp nor gelE was necessary for biofilm
      formation and this relationship was species rather than strain specific. This
      study emphasizes the importance of enterococci as a reservoir of virulence genes
      and the potential for their genetic transfer to human strains following
      consumption of uncooked or undercooked contaminated meat. 

PMID- 24291184
TI  - Inhibition of ochratoxigenic moulds by Debaryomyces hansenii strains for
      biopreservation of dry-cured meat products.
AB  - The ability of the osmotolerant yeast Debaryomyces hansenii to inhibit
      Penicillium nordicum, the most common ochratoxigenic mould encountered in dry
      cured meat products, was evaluated. The antagonistic effect of ten D. hansenii
      strains isolated from dry-cured ham was screened in vitro using malt extract
      media and meat extract peptone media with the water activity (a(w)) adjusted to
      0.97 and 0.90. A significant inhibition of the two tested P. nordicum strains by
      D. hansenii cells and cell-free supernatants was observed. At 0.97 a(w),
      increasing D. hansenii inoculum concentrations significantly improved the
      inhibition of mould growth on solid medium, whereas at 0.90 a(w) this was not
      always the case. As observed by bright field microscopy, most D. hansenii strains
      were able to delay P. nordicum spore germination when co-cultured in malt extract
      broth. D. hansenii FHSCC 253H showed the highest overall in vitro inhibition of
      ochratoxigenic mould growth, and was therefore chosen for co-cultivation assays
      in dry-cured ham slices incubated at 0.94 and 0.84 a(w) simulating ham ripening.
      Regardless of the experimental conditions tested, lower levels of the inoculated
      P. nordicum strain were detected in co-cultivation batches compared with batches
      without D. hansenii. The highest level of mould growth inhibition was observed in
      batches at 0.94 a(w). Ochratoxin A (OTA) production in ham samples was detected
      by HPLC-MS. Co-culturing of P. nordicum with D. hansenii FHSCC 253H resulted in
      lower OTA levels compared with control samples without D. hansenii. The decrease
      of the mycotoxin presence due to D. hansenii FHSCC 253H was more efficient at
      0.94 a(w) (OTA was below the detection limit). In conclusion, D. hansenii is
      potentially suitable as a biopreservative agent for preventing ochratoxigenic
      mould growth and OTA accumulation in dry-cured meat products. The inoculation of
      D. hansenii should be made at the beginning of processing (at the end of post
      salting) when the a(w) of the product is still high (near 0.94). This action in
      addition to application of appropriate hygienic actions and control of
      temperature and relative humidity throughout ripening is required to reduce
      health risks due to OTA exposure.

PMID- 24291185
TI  - Error analysis in predictive modelling demonstrated on mould data.
AB  - The purpose of this paper was to develop a predictive model for the effect of
      temperature and water activity on the growth rate of Aspergillus niger and to
      determine the sources of the error when the model is used for prediction.
      Parallel mould growth curves, derived from the same spore batch, were generated
      and fitted to determine their growth rate. The variances of replicate ln(growth
      rate) estimates were used to quantify the experimental variability, inherent to
      the method of determining the growth rate. The environmental variability was
      quantified by the variance of the respective means of replicates. The idea is
      analogous to the "within group" and "between groups" variability concepts of
      ANOVA procedures. A (secondary) model, with temperature and water activity as
      explanatory variables, was fitted to the natural logarithm of the growth rates
      determined by the primary model. The model error and the experimental and
      environmental errors were ranked according to their contribution to the total
      error of prediction. Our method can readily be applied to analysing the error
      structure of predictive models of bacterial growth models, too. 

PMID- 24291186
TI  - Probabilistic model for the spoilage wine yeast Dekkera bruxellensis as a
      function of pH, ethanol and free SO2 using time as a dummy variable.
AB  - The present study uses a probabilistic model to determine the growth/no growth
      interfaces of the spoilage wine yeast Dekkera bruxellensis CH29 as a function of
      ethanol (10-15%, v/v), pH (3.4-4.0) and free SO2 (0-50 mg/l) using time (7, 14,
      21 and 30 days) as a dummy variable. The model, built with a total of 756
      growth/no growth data obtained in a simile wine medium, could have application in
      the winery industry to determine the wine conditions needed to inhibit the growth
      of this species. Thereby, at 12.5% of ethanol and pH 3.7 for a growth probability
      of 0.01, it is necessary to add 30 mg/l of free SO2 to inhibit yeast growth for 7
      days. However, the concentration of free SO2 should be raised to 48 mg/l to
      achieve a probability of no growth of 0.99 for 30 days under the same wine
      conditions. Other combinations of environmental variables can also be determined
      using the mathematical model depending on the needs of the industry.

PMID- 24291187
TI  - Enhanced inactivation of Escherichia coli and Listeria monocytogenes by exposure
      to 405 nm light under sub-lethal temperature, salt and acid stress conditions.
AB  - The antimicrobial effects of 405 nm light have generated interest in its use as
      an emerging disinfection technology with potential food-related applications. The
      aim of this study was to assess the bactericidal efficacy of 405 nm light for
      inactivation of Escherichia coli and Listeria monocytogenes under sub-lethally
      stressed environmental conditions. Bacteria were exposed to 405 nm light from a
      light emitting diode (LED) array under various temperature, salt (NaCl) and acid
      conditions to determine if bacterial susceptibility to 405 nm light inactivation
      is affected when exposed under these conditions. Non-stressed bacterial
      populations (10(5) CFU/mL) were exposed to increasing doses of 405 nm light (~70
      mW/cm(2)) and the inactivation results were compared with those generated under
      stress conditions. Bacteria were held at various temperatures (4 degrees C, 22
      degrees C and 45 degrees C), acid concentrations (pH3, 3.5 and 7) and salt
      concentrations (0%, 0.8%, 10% and 15% NaCl), and simultaneously exposed to 405 nm
      light. Enhanced inactivation of both E. coli and L. monocytogenes was achieved
      when light exposure was combined with each of the sub-lethal stresses, with
      significantly increased inactivation rates compared to non-stressed populations
      (P<=0.05). One exception was with L. monocytogenes when light-exposed in the
      presence of 15% salt, as this combination reduced bacterial inactivation. The
      greatest enhancement of 405 nm light inactivation for both bacterial species was
      achieved when light exposure was combined with sub-lethal acid stress conditions
      at pH3. This was demonstrated by a 5-log10 reduction of E. coli following a 405
      nm light dose of 84 J/cm(2) compared to 378 J/cm(2) for non-stressed populations
      (77% reduction in dose) and by a 5-log10 reduction of L. monocytogenes achieved
      with a dose of 42 J/cm(2) which corresponded to 50% of the dose required for the
      equivalent reduction of non-stressed populations. This acid-enhanced 405 nm light
      inactivation effect was demonstrated with E. coli and L. monocytogenes when
      dispersed in liquid suspension and when deposited on a test surface. Overall,
      results from this study have shown that sub-lethally stressed bacteria have
      increased susceptibility to 405 nm light inactivation, thereby providing a
      synergistic inactivation effect, findings which increase the potential of this
      new light-based decontamination technology for food related applications.

PMID- 24291188
TI  - Ectopic expression of ZmSIMK1 leads to improved drought tolerance and activation
      of systematic acquired resistance in transgenic tobacco.
AB  - The mitogen-activated protein kinase (MAPK) cascades play pivotal roles in
      diverse signaling pathways related to plant biotic and abiotic stress responses.
      In this study, a group B MAPK gene in Zea mays, ZmSIMK1, was functionally
      analyzed. Quantitative real-time PCR (qRT-PCR) analysis indicated that ZmSIMK1
      transcript could be induced by drought, salt, Pseudomonas syringae pv. tomato
      DC3000 (Pst DC3000) and certain exogenous signaling molecules. Analysis of the
      ZmSIMK1 promoter revealed a group of putative cis-acting elements related to
      drought and defense responses. beta-Glucuronidase (GUS) staining produced similar
      results as qRT-PCR. ZmSIMK1 was mainly localized in the nucleus, and further
      study indicated that the C-terminal domain (CD) was essential for targeting to
      the nucleus. Transgenic tobacco accumulated less reactive oxygen species (ROS),
      had higher levels of antioxidant enzyme activity and osmoregulatory substances
      and exhibited an increased germination rate compared with wild-type (WT) tobacco
      under drought stress. ROS-related and drought stress-responsive genes in
      transgenic tobacco were significantly upregulated compared with the same genes in
      WT lines under drought stress. Moreover, overexpression of ZmSIMK1 promoted the
      hypersensitive response (HR) and pathogen-related gene (PR) transcription in
      addition to triggering systemic acquired resistance (SAR) in tobacco. 

PMID- 24291189
TI  - Stereoselective synthesis of (R)-phenylephrine using recombinant Escherichia coli
      cells expressing a novel short-chain dehydrogenase/reductase gene from Serratia
      marcescens BCRC 10948.
AB  - (R)-Phenylephrine [(R)-PE] is an alpha1-adrenergic receptor agonist and is widely
      used as a nasal decongestant to treat the common cold without the side effects of
      other ephedrine adrenergic drugs. We identified a short-chain
      dehydrogenase/reductase (SM_SDR) from Serratia marcescens BCRC 10948 that was
      able to convert 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) into (R)-PE.
      The SM_SDR used NADPH and NADH as cofactors with specific activities of 17.35+/
      0.71 and 5.57+/-0.07mU/mg protein, respectively, at 30 degrees C and pH 7.0,
      thereby indicating that this enzyme could be categorized as an NADPH-preferring
      short-chain dehydrogenase/reductase. Escherichia coli strain BL21 (DE3)
      expressing SM_SDR could convert HPMAE into (R)-PE with more than 99% enantiomeric
      excess. The productivity and conversion yield were 0.57mmolPE/lh and 51.06%,
      respectively, using 10mM HPMAE. Fructose was the most effective carbon source for
      the conversion of HPMAE to (R)-PE. 

PMID- 24291190
TI  - Innovative use of Mucuna monosperma (Wight) callus cultures for continuous
      production of melanin by using statistically optimized biotransformation medium.
AB  - Melanins are predominantly indolic polymers which are having extensive
      applications in cosmetics, agriculture and medicine. In the present study,
      optimization of nutritional parameters influencing melanin production by Mucuna
      monosperma callus cultures was attempted using the response surface methodology
      (RSM). Standardization of four factors was carried out using the Box-Behnken
      design. The optimized levels of factors predicted by the model include tyrosine
      0.978gL(-1), pH 5.85, SDS 34.55mgL(-1)and copper sulphate 21.14mgL(-1) tyrosine,
      which resulted in highest melanin yield of 0.887gL(-1). The optimization of
      medium using RSM resulted in a 3.06-fold increase in the yield of melanin. The
      ANOVA analysis showed a significant R(2)-value (0.9995), model F-value (1917.72)
      and probability (0.0001), with insignificant lack of fit. Optimized medium was
      used in the laboratory scale column reactor for the continuous production of
      melanin. Uninterrupted flow column exhibited maximum melanin production rate of
      250mgL(-1)h(-1) which is the highest value ever reported using plant as a
      biotransformation source. Melanin production was confirmed by spectrophotometric
      and chemical analysis. Thus, this study demonstrates the production of melanin by
      M. monosperma callus, using a laboratory scale column reactor. 

PMID- 24291191
TI  - A Pasteurella multocida sialyltransferase displaying dual trans-sialidase
      activities for production of 3'-sialyl and 6'-sialyl glycans.
AB  - This study examined a recombinant Pasteurella multocida sialyltransferase
      exhibiting dual trans-sialidase activities. The enzyme catalyzed trans
      sialylation using either 2-O-(p-nitrophenyl)-alpha-d-N-acetylneuraminic acid or
      casein glycomacropeptide (whey protein) as the sialyl donor and lactose as the
      acceptor, resulting in production of both 3'-sialyllactose and 6'-sialyllactose.
      This is the first study reporting alpha-2,6-trans-sialidase activity of this
      sialyltransferase (EC 2.4.99.1 and 2.4.99.4). A response surface design was used
      to evaluate the effects of three reaction parameters (pH, temperature, and
      lactose concentration) on enzymatic production of 3'- and 6'-sialyllactoses using
      5% (w/v) casein glycomacropeptide (equivalent to 9mM bound sialic acid) as the
      donor. The maximum yield of 3'-sialyllactose (2.75+/-0.35mM) was achieved at a
      reaction condition with pH 6.4, 40 degrees C, 100mM lactose after 6h; and the
      largest concentration of 6'-sialyllactose (3.33+/-0.38mM) was achieved under a
      condition with pH 5.4, 40 degrees C, 100mM lactose after 8h. 6'-sialyllactose was
      presumably formed from alpha-2,3 bound sialic acid in the casein
      glycomacropeptide as well as from 3'-sialyllactose produced in the reaction. The
      kcat/Km value for the enzyme using 3'-sialyllactose as the donor for 6'
      sialyllactose synthesis at pH 5.4 and 40 degrees C was determined to be 23.22+/
      0.7M(-1)s(-1). Moreover, the enzyme was capable of catalyzing the synthesis of
      both 3'- and 6'-sialylated galactooligosaccharides, when galactooligosaccharides
      served as acceptors. 

PMID- 24291192
TI  - Peroxisome proliferator-activated receptor-alpha activation and excess energy
      burning in hepatocarcinogenesis.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) modulates the
      activities of all three interlinked hepatic fatty acid oxidation systems, namely
      mitochondrial and peroxisomal beta-oxidation and microsomal omega-oxidation
      pathways. Hyperactivation of PPARalpha, by both exogenous and endogenous
      activators up-regulates hepatic fatty acid oxidation resulting in excess energy
      burning in liver contributing to the development of liver cancer in rodents.
      Sustained PPARalpha signaling disproportionately increases H2O2-generating fatty
      acid metabolizing enzymes as compared to H2O2-degrading enzymes in liver leading
      to enhanced generation of DNA damaging reactive oxygen species, progressive
      endoplasmic reticulum stress and inflammation. These alterations also contribute
      to increased liver cell proliferation with changes in apoptosis. Thus, reactive
      oxygen species, oxidative stress and hepatocellular proliferation are likely the
      main contributing factors in the pathogenesis of hepatocarcinogenesis, mediated
      by sustained PPARalpha activation-related energy burning in liver. Furthermore,
      the transcriptional co-activator Med1, a key subunit of the Mediator complex, is
      essential for PPARalpha signaling in that both PPARalpha-null and Med1-null
      hepatocytes are unresponsive to PPARalpha activators and fail to give rise to
      liver tumors when chronically exposed to PPARalpha activators. 

PMID- 24291194
TI  - Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized
      dose response study.
AB  - Probiotics are known to reduce antibiotic associated diarrhea (AAD) and
      Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific
      manner. The aim of this study was to determine the dose-response effect of a four
      strain probiotic combination (HOWARU((r)) Restore) on the incidence of AAD and
      CDAD and severity of gastrointestinal symptoms in adult in-patients requiring
      antibiotic therapy. Patients (n=503) were randomized among three study groups:
      HOWARU((r)) Restore probiotic 1.70*10(10) CFU (high-dose, n=168), HOWARU((r))
      Restore probiotic 4.17*10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects
      were stratified by gender, age, and duration of antibiotic treatment. Study
      products were administered daily up to 7 days after the final antibiotic dose.
      The primary endpoint of the study was the incidence of AAD. Secondary endpoints
      included incidence of CDAD, diarrhea duration, stools per day, bloody stools,
      fever, abdominal cramping, and bloating. A significant dose-response effect on
      AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low
      dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic
      groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of
      fever, abdominal pain, and bloating were lower with increasing probiotic dose.
      The number of daily liquid stools and average duration of diarrhea decreased with
      higher probiotic dosage. The tested four strain probiotic combination appears to
      lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent
      manner in adult in-patients. 

PMID- 24291193
TI  - Impact of malaria and helminth infections on immunogenicity of the human
      papillomavirus-16/18 AS04-adjuvanted vaccine in Tanzania.
AB  - BACKGROUND: Endemic malaria and helminth infections in sub-Saharan Africa can act
      as immunological modulators and impact responses to standard immunizations. We
      conducted a cohort study to measure the influence of malaria and helminth
      infections on the immunogenicity of the bivalent HPV-16/18 vaccine. METHODS: We
      evaluated the association between malaria and helminth infections, and HPV-16/18
      antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a
      randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was
      diagnosed by examination of blood smears, and helminth infections were diagnosed
      by examination of urine and stool samples, respectively. Geometric mean antibody
      titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked
      immunosorbent assay. RESULTS: Parasitic infections were common; one-third (30.4%)
      of participants had a helminth infection and 10.2% had malaria parasitaemia.
      Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a
      reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among
      participants with helminths or malaria. There was some evidence that participants
      with malaria had increased GMTs compared to those without malaria. CONCLUSIONS:
      The data show high HPV immunogenicity regardless of the presence of malaria and
      helminth infections. The mechanism and significance for the increase in GMT in
      those with malaria is unknown.

PMID- 24291195
TI  - A monoclonal antibody that recognizes the E domain of staphylococcal protein A.
AB  - Staphylococcal protein A (SpA) binds Fcgamma and VH3 clan Fab domains of human
      and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs),
      thereby supporting Staphylococcus aureus escape from opsonophagocytic killing and
      suppressing adaptive B cell responses. The variant SpAKKAA cannot bind Ig yet
      retains antigenic properties that elicit SpA-neutralizing antibodies and disease
      protection in mice, whereas S. aureus infection or SpA-immunization cannot elicit
      neutralizing antibodies. As a test for this model, we analyzed here mAb 358A76,
      which was isolated from SpA-immunized mice. Unlike SpAKKAA-derived mAbs, mAb
      358A76 binds only the first IgBD (E) but not any of the other four IgBDs (D-A-B
      C) and its binding can neutralize only the E domain of SpA, which does not
      provide disease protection in mice. These results are in agreement with a model
      whereby wild-type SpA-immunization generates a limited antibody response without
      neutralizing and/or disease protective attributes. 

PMID- 24291196
TI  - Engineered Lactobacillus rhamnosus GG expressing IgG-binding domains of protein
      G: Capture of hyperimmune bovine colostrum antibodies and protection against
      diarrhea in a mouse pup rotavirus infection model.
AB  - Rotavirus-induced diarrhea causes more than 500,000 deaths annually in the world,
      and although vaccines are being made available, new effective treatment
      strategies should still be considered. Purified antibodies derived from
      hyperimmune bovine colostrum (HBC), from cows immunized with rotavirus, were
      previously used for treatment of rotavirus diarrhea in children. A combination of
      HBC antibodies and a probiotic strain of Lactobacillus (L. rhamnosus GG) was also
      found to be more effective than HBC alone in reducing diarrhea in a mouse model
      of rotavirus infection. In order to further improve this form of treatment, L.
      rhamnosus GG was engineered to display surface expressed IgG-binding domains of
      protein G (GB1, GB2, and GB3) which capture HBC-derived IgG antibodies (HBC-IgG)
      and thus target rotavirus. The expression of IgG-binding domains on the surface
      of the bacteria as well as their binding to HBC-IgG and to rotavirus (simian
      strain RRV) was demonstrated by Western blot, flow cytometry, and electron
      microscopy. The prophylactic effect of engineered L. rhamnosus GG and anti
      rotaviral activity of HBC antibodies was evaluated in a mouse pup model of RRV
      infection. The combination therapy with engineered L. rhamnosus GG (PG3) and HBC
      was significantly more effective in reducing the prevalence, severity, and
      duration of diarrhea in comparison to HBC alone or a combination of wild-type L.
      rhamnosus GG and HBC. The new therapy reduces the effective dose of HBC between
      10 to 100-fold and may thus decrease treatment costs. This antibody capturing
      platform, tested here for the first time in vivo, could potentially be used to
      target additional gastrointestinal pathogens. 

PMID- 24291197
TI  - DNA vaccination against a fish rhabdovirus promotes an early chemokine-related
      recruitment of B cells to the muscle.
AB  - In fish, intramuscular (i.m) injection of plasmid DNA encoding viral proteins has
      proved a highly effective vaccination strategy against some viral pathogens. The
      efficacy of DNA vaccination in teleost fish is based on the high level of viral
      antigen expression in muscle cells inducing a strong and long-lasting protection.
      However, the mechanisms through which this protection is established and
      effectuated in fish are still not fully understood. Moreover, similarities to
      mammalian models cannot be established since DNA vaccination in mammals usually
      induces much weaker responses. In this work, we have focused on the
      characterization of the immune cells that infiltrate the muscle at the site of
      DNA injection in vaccinated fish and the chemokines and chemokine receptors that
      may be involved in their infiltration. We have demonstrated through diverse
      techniques that B lymphocytes, both IgM+ and IgT+ cells, represented a major
      infiltrating cell type in fish vaccinated with a viral haemorrhagic septicaemia
      virus (VHSV) glycoprotein-encoding DNA vaccine, whereas in control fish injected
      with an oil adjuvant mainly granulocyte/monocyte-type cells were attracted. Among
      twelve chemokine genes studied, only CXCL11_L1, CK5B and CK6 mRNA levels were up
      regulated in DNA vaccinated fish compared to fish injected with the corresponding
      vector backbone. Furthermore, the transcription of CXCR3B, a possible receptor
      for CXCL11_L1 was also significantly up-regulated in vaccinated fish. Finally,
      experiments performed with recombinant trout CK5B and CK6 and chemokine
      expression plasmids revealed that these chemokines have chemotactic capacities
      which might explain the recruitment of B cells to the site of DNA injection.
      Altogether, our results reveal that there is an early chemokine-related B cell
      recruitment triggered by i.m. DNA vaccination against VHSV which might play an
      important role in the initial phase of the immune response.

PMID- 24291198
TI  - Disease-related adverse events following non-live vaccines: investigation of a
      newly described reporting bias through the analysis of the WHO Global ICSR
      Database, VigiBase.
AB  - Due to a vaccine-specific reporting bias, it has been recently suggested that
      some non-live vaccines may be preferentially reported as the suspected cause of
      the disease or symptoms/signs related to the disease they should prevent. The aim
      of this study was to analyse the WHO Global Individual Case Safety Report (ICSR)
      Database, VigiBase, in order to explore this newly described reporting bias in
      greater detail and to verify whether it can generate potentially misleading
      signals of disproportionate reporting (SDRs). Vaccines reports entered into
      VigiBase between 1990 and 2011 were extracted. Twelve non-combined non-live
      vaccines were chosen for analysis. Two distinct groups of MedDRA preferred terms
      (PTs) per vaccine were selected on the basis of the disease-specificity. Twenty
      four vaccine-events pairs were obtained and referred as "misleading
      combinations". A descriptive analysis of the reports retrieved was performed. To
      verify whether a specific group of selected PTs was disproportionally reported in
      association with the vaccine representing the respective "misleading
      combination", the reporting odds ratio (ROR) was calculated for each of the 24
      vaccine-event pairs retrieved considering all the other vaccines as the
      background. A total of 627,165 reports were analysed. Among ICSRs containing a
      "misleading combination", healthcare professionals were the most frequently noted
      (17%), though reporter type was unknown in 72% of the remaining reports. The
      reporting rate distribution of the 24 groups of PTs per vaccine included in the
      study showed that in 16 cases the highest rate was reached by the vaccine
      representing the respective "misleading combination". The application of the ROR
      yielded 21 SDRs out of 24 combinations tested. Findings from this study support
      the existence of a vaccine-specific reporting bias. Since this phenomenon may
      result in potentially misleading SDRs, professionals involved in vaccine safety
      surveillance should also consider this bias during the validation of such
      disproportional associations. 

PMID- 24291199
TI  - Memory CD8(+) T cells elicited by HIV-1 lipopeptide vaccines display similar
      phenotypic profiles but differences in term of magnitude and multifunctionality
      compared with FLU- or EBV-specific memory T cells in humans.
AB  - Differentiation marker, multifunctionality and magnitude analyses of specific
      CD8(+) memory T cells are crucial to improve development of HIV vaccines designed
      to generate cell-mediated immunity. Therefore, we fully characterized the HIV
      specific CD8(+) T cell responses induced in volunteers vaccinated with HIV
      lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine
      secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells
      elicited by lipopeptide vaccines is very rare and central-memory phenotype and
      functions of these cells were been shown to be important in AIDS immunity. So, we
      expanded them using specific peptides to compare the memory T cell responses
      induced in volunteers by HIV vaccines with responses to influenza (FLU) or
      Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-gamma
      secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile
      (>85%) belonging to a subset of intermediate-differentiated effector T cells for
      HIV, FLU, and EBV. We then assessed the quality of the response by measuring
      various T cell functions. The percentage of single IFN-gamma T cell producers in
      response to HIV was 62% of the total of secreting T cells compared with 35% for
      FLU and EBV, dual and triple (IFN-gamma/IL-2/CD107a) T cell producers could also
      be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T
      cells secreted IFN-gamma and TNF-alpha, but not the dual combination like FLU-
      and EBV-specific T cells. Thus, we found that the functional profile and
      magnitude of expanded HIV-specific CD8(+) T precursors were more limited than
      those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T
      cells induced by these HIV vaccines have a similar differentiation profile to FLU
      and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T
      cells needs to be increased in order to improve vaccination strategies. 

PMID- 24291200
TI  - Estimation of the potential overall impact of human papillomavirus vaccination on
      cervical cancer cases and deaths.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccination offers potential for primary
      prevention of HPV-related pre-cancers and cancers as demonstrated in clinical
      trials. Mathematical models have estimated the potential real-life impact of
      vaccination on the burden of cervical cancer (CC). However, these are restricted
      to evaluations in a limited number of countries. METHODS: Potential decline in CC
      cases and deaths with the AS04-adjuvanted HPV-16/18 vaccine of young girls naive
      to HPV, was estimated at steady-state (vaccine coverage: 0-100%) based on
      clinical trial and country-specific incidence data. Data on vaccine efficacy were
      taken from the end of study PATRICIA trial of the AS04-adjuvanted HPV-16/18
      vaccine. The numbers of cases and deaths due to HPV-16/18 were estimated and
      compared with those due to any HPV type to estimate the additional cases
      prevented. This difference estimates CC cases and deaths avoided due to
      protection against non-vaccine HPV types. Cost-offsets due to reductions in CC
      treatment were estimated for five countries (Brazil, Canada, Italy, Malaysia and
      South African Republic) using country-specific unit cost data. Additionally,
      cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3)-related burden (cases
      and treatment costs) prevented by vaccination were estimated for two countries
      (Italy and Malaysia). RESULTS: HPV vaccination could prevent a substantial number
      of CC cases and deaths in countries worldwide, with associated cost-offsets due
      to reduced CC treatment. Cross-protection increased the estimated potential
      number of CC cases and deaths prevented by 34 and 18% in Africa and Oceania,
      respectively. Moreover, vaccination could result in a substantial reduction in
      the number of CIN2/3 lesions and associated costs. CONCLUSION: HPV vaccination
      could reduce the burden of CC and precancerous lesions in countries worldwide,
      part of disease burden reduction being related to protection against non HPV
      16/18 related types.

PMID- 24291201
TI  - Influenza vaccination and risk of hospitalization among adults with laboratory
      confirmed influenza illness.
AB  - BACKGROUND: Influenza vaccine is moderately effective for preventing influenza
      illness. It is not known if vaccination reduces the risk of subsequent hospital
      admission among patients with vaccine failure and laboratory confirmed influenza
      illness. METHODS: Patients in a community cohort presenting with acute
      respiratory illness were prospectively enrolled and tested for influenza during 8
      seasons to estimate seasonal vaccine effectiveness. Hospital admissions within 14
      days after illness onset were identified for all participants aged >=20 years
      with laboratory confirmed influenza. The association between vaccination and
      hospital admission was examined in a propensity score adjusted logistic
      regression model. The model was validated by examining the association between
      vaccination and hospital admission in participants without influenza. RESULTS:
      Influenza was identified in 1393 (28%) of 4996 participants. Sixty-two (6%) of
      1020 with influenza A and 17 (5%) of 369 with influenza B were hospitalized.
      Vaccination was not associated with a reduced risk of hospital admission among
      all participants with influenza [adjusted odds ratio (aOR)=1.08; 95% CI: 0.62,
      1.88]; or among those with influenza A (aOR=1.35; 95% CI: 0.71, 2.57) or
      influenza B (aOR=0.67; 95% CI: 0.21, 2.15). Influenza vaccination was not
      associated with hospitalization after non-influenza respiratory illness
      (aOR=1.14; 95% CI: 0.84, 1.54). CONCLUSIONS: Influenza vaccination did not reduce
      the risk of subsequent hospital admission among patients with vaccine failure.
      These findings do not support the hypothesis that vaccination mitigates influenza
      illness severity.

PMID- 24291202
TI  - Quantitative real-time PCR eliminates false-positives in colony screening PCR.
AB  - We report an alternative approach to colony screening using real-time PCR (qPCR)
      which can be used instead of the traditional end-point PCR to eliminate false
      positives and reduce processing times. False-positive transformants can easily be
      distinguished from true-positives by comparing Ct values derived from qPCR
      amplification curves. In addition, the use of qPCR allows for more efficient
      processing since a gel electrophoresis step is not required and the screening
      process is no longer limited by the capacity of the gel apparatus. 

PMID- 24291203
TI  - A United Kingdom perspective on the relationship between body mass index (BMI)
      and bone health: a cross sectional analysis of data from the Nottingham Fracture
      Liaison Service.
AB  - OBJECTIVES: This study examines the relationship between high BMI, a diagnosis of
      osteoporosis and low trauma fractures. METHOD: This is a cross sectional analysis
      using data collected from the Nottingham Fracture Liaison Service. A total of
      4288 participants with a low trauma fracture from 1 January 2007 to 31 August
      2012 were analysed. Logistic regression adjusted for potential confounders was
      used investigate osteoporosis and BMI. Fracture types were compared between those
      who were obese and non-obese. RESULTS: A total of 30% (1285) were obese.
      Prevalence of osteoporosis was 13.4%, 24.9%, and 40.4% in the obese, overweight
      and normal category respectively. Being obese has an odds ratio of 0.23 (95% CI
      0.19-0.28, p<0.01) of having osteoporosis compared to a normal BMI category. When
      variable BMI cut offs were used (BMI 25, 30 and 35) to calculate the positive
      predictive value of patients not having osteoporosis, it was 80.5%, 86.3% and
      88.3%. Examining fracture types, obese patients when compared with the non-obese
      category, were more likely to fracture their ankle (OR 1.48, p<0.01) and upper
      arm (OR 1.48, p<0.001), but were less likely to fracture their wrist (OR 0.65,
      p<0.001). In the elderly (>70years), obesity no longer influenced ankle or wrist
      fractures but there is an increased risk of upper arm fractures (OR 1.46,
      p=0.005). CONCLUSION: Higher BMD in obesity is not protective against fractures
      as there are a significant number of fractures in this group which may be due to
      body habitus, mechanism of injury and the effect of adiposity on bone. A low
      trauma osteoporotic fracture will need to be redefined in light of these
      findings.

PMID- 24291204
TI  - Chromosome 10q26 locus and age-related macular degeneration: a progress update.
AB  - Age-related macular degeneration (AMD) is the leading cause of late-onset central
      vision loss in developed countries. Both genetic and environmental factors
      contribute to the onset of AMD. Variation at a locus on chromosome 10q26 has been
      consistently associated with this disease and represents one of the two strongest
      genetic effects being identified in AMD. At least three genes are located within
      the bounds of the locus: pleckstrin homology domain containing family A member 1
      (PLEKHA1), age-related maculopathy susceptibility 2 (ARMS2) and high-temperature
      requirement A serine peptidase 1 (HTRA1), all of which are associated with AMD.
      Due to the strong linkage disequilibrium (LD) across this region, statistical
      genetic analysis alone is incapable of distinguishing the effect of an individual
      gene in the locus. Uncertainty remains, however, in regards to which gene is
      responsible for the linkage and association of the locus with AMD. Investigating
      functional consequences of the associated variants and related genes tends to be
      essential to identifying the biologically responsible gene(s) underlying AMD.
      This review examines the recent progress and current uncertainty on the genetic
      and functional analyses of the 10q26 locus in AMD with a focus on ARMS2 and
      HTRA1. A discussion, which entails the possible multi-faceted approaches for
      pinpointing the gene(s) in the locus underlying the pathogenesis of AMD, is also
      included. 

PMID- 24291205
TI  - Parametric model for the 3D reconstruction of individual fovea shape from OCT
      data.
AB  - As revealed by optical coherence tomography (OCT), the shape of the fovea may
      vary greatly among individuals. However, none of the hitherto available
      mathematical descriptions comprehensively reproduces all individual
      characteristics such as foveal depth, slope, naso-temporal asymmetry, and others.
      Here, a novel mathematical approach is presented to obtain a very accurate model
      of the complete 3D foveal surface of an individual, by utilizing recent
      developments in OCT. For this purpose, a new formula was developed serving as a
      simple but very flexible way to represent a given fovea. An extensive description
      of the used model parameters, as well as, of the complete method of
      reconstructing a foveal surface from OCT data, is presented. Noteworthy, the
      formula analytically provides characteristic foveal parameters and thus allows
      for extensive quantification. The present approach was verified on 432 OCT scans
      and has proved to be able to capture the whole range of asymmetric foveal shapes
      with high accuracy (i.e. a mean fit error of 1.40 MUm). 

PMID- 24291206
TI  - Long-term effects of prenatal allopurinol treatment on brain plasticity markers
      in low and normal birth weight piglets.
AB  - In this study, we investigated the effect of antenatal allopurinol (ALLO)
      treatment on levels and expression of plasticity markers in the dorsal
      hippocampus of low (LBW) and normal (NBW) birth weight piglets. ALLO treatment
      given daily in the last trimester to pregnant sows had a protective effect on
      neuronal plasticity markers in their piglets. ALLO increases protein levels of
      BDNF and the postsynaptic marker PSD95 in LBW and NBW piglets. ALLO treatment
      increases the pCREB/CREB ratio in LBW piglets to a similar level as that found in
      untreated NBW piglets. In conclusion, antioxidant treatment administered in the
      last trimester might be a promising treatment for LBW neonates. 

PMID- 24291207
TI  - Successful laparoscopic removal of adnexal mass in a patient with a large ventral
      hernia.

PMID- 24291208
TI  - Reply to Dr. Ozturk.

PMID- 24291209
TI  - Laparoscopic modified sacral hysteropexy: initial experience with an original
      surgical approach to uterovaginal prolapse.
AB  - STUDY OBJECTIVE: To evaluate the feasibility of a modified laparoscopic approach
      to correct uterovaginal prolapse using cervical cerclage tape to attach the
      uterine isthmus to the sacral promontory. DESIGN: Retrospective study (Canadian
      Task Force classification III). SETTING: Tertiary referral center. PATIENTS: From
      January 2011 to February 2013, 33 patients underwent laparoscopic modified sacral
      hysteropexy with use of cervical cerclage tape at West China Second University
      Hospital. All patients had stage 2 to 4 uterovaginal prolapse according to the
      Pelvic Organ Prolapse Quantification System. MEASUREMENTS AND MAIN RESULTS: The
      outcome was assessed via preoperative and postoperative pelvic examinations, and
      the surgical results were evaluated. The mean operative time was 90.0 minutes,
      and blood loss was 80.5 mL. No intraoperative or postoperative complications
      occurred. At the minimum 6-month follow up, all patients had prolapse of stage I
      or lower. CONCLUSIONS: After larger trials are performed to assess the safety and
      efficacy of this modified laparoscopic sacral hysteropexy, this novel approach
      might be considered as an alternative treatment option in patients with
      uterovaginal prolapse.

PMID- 24291211
TI  - Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial
      activation in discrete regions of the hypothalamus and the subfornical organ.
AB  - Calorie restriction (CR) has been shown to increase longevity and elicit many
      health promoting benefits including delaying immunosenescence and attenuating
      neurodegeneration in animal models of Alzheimer's disease and Parkinson's
      disease. CR also suppresses microglial activation following cortical injury and
      aging. We previously demonstrated that CR attenuates lipopolysaccharide (LPS)
      induced fever and shifts hypothalamic signaling pathways to an anti-inflammatory
      bias; however, the effects of CR on LPS-induced microglial activation remain
      largely unexplored. The current study investigated regional changes in LPS
      induced microglial activation in mice exposed to 50% CR for 28days.
      Immunohistochemistry was conducted to examine changes in ionized calcium-binding
      adapter molecule-1 (Iba1), a protein constitutively expressed by microglia, in a
      total of 27 brain regions involved in immunity, stress, and/or thermoregulation.
      Exposure to CR attenuated LPS-induced fever, and LPS-induced microglial
      activation in a subset of regions: the arcuate nucleus (ARC) and ventromedial
      nucleus of the hypothalamus (VMH) and the subfornical organ (SFO). Microglial
      activation in the ARC and VMH was positively correlated with body temperature.
      These data suggest that CR exerts effects on regionally specific populations of
      microglia; particularly, in appetite-sensing regions of the hypothalamus, and/or
      regions lacking a complete blood brain barrier, possibly through altered pro- and
      anti-inflammatory signaling in these regions. 

PMID- 24291210
TI  - D-polyglutamine amyloid recruits L-polyglutamine monomers and kills cells.
AB  - Polyglutamine (polyQ) amyloid fibrils are observed in disease tissue and have
      been implicated as toxic agents responsible for neurodegeneration in expanded CAG
      repeat diseases such as Huntington's disease. Despite intensive efforts, the
      mechanism of amyloid toxicity remains unknown. As a novel approach to probing
      polyQ toxicity, we investigate here how some cellular and physical properties of
      polyQ amyloid vary with the chirality of the glutamine residues in the polyQ. We
      challenged PC12 cells with small amyloid fibrils composed of either L- or D-polyQ
      peptides and found that D-fibrils are as cytotoxic as L-fibrils. We also found
      using fluorescence microscopy that both aggregates effectively seed the
      aggregation of cell-produced L-polyQ proteins, suggesting a surprising lack of
      stereochemical restriction in seeded elongation of polyQ amyloid. To investigate
      this effect further, we studied chemically synthesized D- and L-polyQ in vitro.
      We found that, as expected, D-polyQ monomers are not recognized by proteins that
      recognize L-polyQ monomers. However, amyloid fibrils prepared from D-polyQ
      peptides can efficiently seed the aggregation of L-polyQ monomers in vitro, and
      vice versa. This result is consistent with our cell results on polyQ recruitment
      but is inconsistent with previous literature reports on the chiral specificity of
      amyloid seeding. This chiral cross-seeding can be rationalized by a model for
      seeded elongation featuring a "rippled beta-sheet" interface between seed fibril
      and docked monomers of opposite chirality. The lack of chiral discrimination in
      polyQ amyloid cytotoxicity is consistent with several toxicity mechanisms,
      including recruitment of cellular polyQ proteins.

PMID- 24291212
TI  - Systems biology and the analysis of genetic variation.

PMID- 24291213
TI  - Universality and predictability in molecular quantitative genetics.
AB  - Molecular traits, such as gene expression levels or protein binding affinities,
      are increasingly accessible to quantitative measurement by modern high-throughput
      techniques. Such traits measure molecular functions and, from an evolutionary
      point of view, are important as targets of natural selection. We review recent
      developments in evolutionary theory and experiments that are expected to become
      building blocks of a quantitative genetics of molecular traits. We focus on
      universal evolutionary characteristics: these are largely independent of a
      trait's genetic basis, which is often at least partially unknown. We show that
      universal measurements can be used to infer selection on a quantitative trait,
      which determines its evolutionary mode of conservation or adaptation.
      Furthermore, universality is closely linked to predictability of trait evolution
      across lineages. We argue that universal trait statistics extends over a range of
      cellular scales and opens new avenues of quantitative evolutionary systems
      biology. 

PMID- 24291215
TI  - Infectious cDNA clones of four viroids in Coleus blumei and molecular
      characterization of their progeny.
AB  - Four viroid species infecting Coleus blumei, named Coleus blumei viroid 1-4 (CbVd
      1-CbVd-4), and two tentative new viroid species, named CbVd-5 and CbVd-6, have
      been characterized, for two of which (CbVd-5 and CbVd-6, first reported in 2009),
      there is no established bioassay. Here, infectious clones were used as inoculums
      sources and the biological properties of CbVd-1, -3, -5 and -6 were assessed.
      When dimeric CbVd (+) RNAs synthesized in vitro were bioassayed, the first
      detection time for the four CbVds was different, ranging from 45 to 300 days. In
      addition, we confirmed that CbVd-5 and CbVd-6 can be transmitted via seeds.
      Molecular characterization of their progeny from slash-inoculated plants one year
      after inoculation demonstrated that the genetic diversity of CbVd populations may
      depend on the infected coleus plants and on the viroid genotype. 

PMID- 24291214
TI  - Qualitative evaluation of a Positive Prevention training for health care
      providers in Mozambique.
AB  - The rapid scale-up of HIV care and treatment in Mozambique has provided an
      opportunity to reach people living with HIV (PLHIV) with prevention interventions
      in HIV care and treatment settings. A three-day Positive Prevention (PP) training
      intervention for health care providers that focused on pressing issues for PLHIV
      in Mozambique was adapted and delivered at sites in three provinces. In-depth
      interviews were conducted with 31 providers trained in the PP curriculum.
      Qualitative data were used to assess the appropriateness of the training
      materials and approach, which lessons providers learned and were able to
      implement and which PP messages were still difficult to deliver. Providers
      reported gaining numerous insights from the training, including how to conduct a
      risk assessment and client-centered counseling, negotiating disclosure, partner
      testing, condom use, PMTCT, treatment adherence and approaches for positive
      living. Training topics not commonly mentioned included discordance counseling,
      STIs, family planning, alcohol and drug use, and frank sexual risk discussions.
      While areas for improvement exist, the PP training was useful in transferring
      skills to providers and is a viable component of HIV care. This evaluation helps
      identify areas where future PP trainings and specific strategies and messages can
      be refined for the Mozambican context. 

PMID- 24291216
TI  - The end of KRAS, and other, cancers? A new way forward.
AB  - Mutant KRAS, as well as other mutant driver genes and epidriver genes, is a
      dominant determinant of resistance to cancer therapeutics. The recent
      introduction of targeting therapies based on drugs that inhibit the kinase
      catalytic function of nodal points along the Ras/extracellular-signal-regulated
      kinase (ERK) and the phosphatidylinositol-3-kinase (PI3K)/Akt cascades is meeting
      with limited success. Against this background, recent evidence shows that the
      beta-galactoside-binding protein (betaGBP) molecule, a physiological PI3K
      inhibitor, is a potent inducer of apoptosis in KRAS-mutant cancer cells (along
      with other aggressive cancer cells of different genetic makeup) and that it is
      therapeutically effective in vivo. Absence of p53 or phosphatase and tensin
      homolog (PTEN) tumor suppressor function or added activating PI3K mutations does
      not affect betaGBP function. In contrast to the concept of one drug against one
      target, betaGBP operates through alternative physiological routes. 

PMID- 24291218
TI  - G8 dementia summit: a chance for united action.

PMID- 24291217
TI  - Treating obesity: is it all in the gut?
AB  - Obesity is a leading cause of preventable mortality worldwide, with current
      strategies for treatment including life-style changes, pharmacological
      intervention and bariatric surgery. With pharmacological intervention showing at
      best modest patient benefits, new treatments are required. Modulation of
      anorectic gut hormones could offer the potential to elicit the required life
      changing level of efficacy only currently seen with bariatric surgery, and
      without the cardiovascular risk associated with a number of the current marketed
      therapies. This review will discuss the gut hormones glucagon-like peptide-1 (GLP
      1), Ghrelin and cholecystokinin (CCK)--for which more advanced non-peptide
      chemical matter has been discovered acting through these hormone pathways and/or
      their receptors.

PMID- 24291219
TI  - Phenotype-genotype complexities: opening DOORS.

PMID- 24291221
TI  - Cell cycle arrest or survival signaling through alphav integrins, activation of
      PKC and ERK1/2 lead to anoikis resistance of ovarian cancer spheroids.
AB  - Ovarian cancer is the most lethal gynecologic cancer mainly due to spheroids
      organization of cancer cells that disseminate within the peritoneal cavity. We
      have investigated the molecular mechanisms by which ovarian cancer spheroids
      resist anoikis, choosing as models the 2 well-characterized human ovarian cancer
      cell lines IGROV1 and SKOV3. These cell lines have the propensity to float as
      clusters, and were isolated from tumor tissue and ascites, respectively. To form
      spheroids, IGROV1 and SKOV3 ovarian adenocarcinoma cells were maintained under
      anchorage-independent culture conditions, in which both lines survive at least a
      week. A short apoptotic period prior to a survival signaling commitment was
      observed for IGROV1 cells whereas SKOV3 cells entered G0/G1 phase of the cell
      cycle. This difference in behavior was due to different signals. With regard to
      SKOV3 cells, activation of p38 and an increase in p130/Rb occurred once anchorage
      independent culture was established. Analyses of the survival signaling pathway
      switched on by IGROV1 cells showed that activation of ERK1/2 was required to
      evade apoptosis, an effect partly dependent on PKC activation and alphav
      integrins. alphav-integrin expression is essential for survival through
      activation of ERK1/2 phosphorylation. The above data indicate that ovarian cancer
      cells can resist anoikis in the spheroid state by arrest in the cell cycle or
      through activation of alphav-integrin-ERK-mediated survival signals. Such
      signaling might result in the selection of resistant cells within disseminating
      spheroids, favoring further relapse in ovarian cancers.

PMID- 24291222
TI  - Differential protein-protein interactions of full length human FasL and FasL
      fragments generated by proteolysis.
AB  - Fas ligand (FasL) is a death factor of the tumor necrosis factor superfamily.
      Like other members of this family of type II transmembrane proteins, FasL is
      subject to ectodomain shedding by a disintegrin and metalloproteinases (ADAMs)
      liberating soluble FasL and leaving membrane-integral N-terminal fragments
      (NTFs). These NTFs are further processed by intramembrane proteolysis through
      signal peptide peptidase-like 2a (SPPL2a), releasing intracellular domains (ICDs)
      which might translocate to the nucleus to regulate transcription. Previous work
      established that the proline-rich domain within the cytosolic N-terminus of FasL
      is required for protein-protein interactions with different Src homology 3 (SH3)
      or WW domain proteins. Distinct binding partners regulate FasL storage and
      surface appearance or are involved in other aspects of FasL biology. Given the
      large number of FasL interactors, we asked whether proteolytically processed FasL
      fragments associate with the same or distinct sets of SH3 domain proteins. To
      address this, we performed co-precipitation experiments using a monoclonal
      antibody directed against the FasL N-terminus for subsequent protein detection of
      full length FasL and NTFs/ICDs in Western blots. We demonstrate that members of
      the sorting nexin (SNX) family bind full length FasL and its N-terminal fragments
      whereas members of the Pombe Cdc15 homology (PCH) protein family bind full length
      FasL, but fail to associate with processed FasL. Thus, we provide first evidence
      that full length FasL and FasL fragments display selectivity regarding their
      association with intracellular binding partners. The differential binding most
      likely governs the fate and function of the intracellular FasL fragments.

PMID- 24291220
TI  - The genetic basis of DOORS syndrome: an exome-sequencing study.
AB  - BACKGROUND: Deafness, onychodystrophy, osteodystrophy, mental retardation, and
      seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown
      cause. We aimed to identify the genetic basis of this syndrome by sequencing most
      coding exons in affected individuals. METHODS: Through a search of available case
      studies and communication with collaborators, we identified families that
      included at least one individual with at least three of the five main features of
      the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual
      disability, and seizures. Participants were recruited from 26 centres in 17
      countries. Families described in this study were enrolled between Dec 1, 2010,
      and March 1, 2013. Collaborating physicians enrolling participants obtained
      clinical information and DNA samples from the affected child and both parents if
      possible. We did whole-exome sequencing in affected individuals as they were
      enrolled, until we identified a candidate gene, and Sanger sequencing to confirm
      mutations. We did expression studies in human fibroblasts from one individual by
      real-time PCR and western blot analysis, and in mouse tissues by
      immunohistochemistry and real-time PCR. FINDINGS: 26 families were included in
      the study. We did exome sequencing in the first 17 enrolled families; we screened
      for TBC1D24 by Sanger sequencing in subsequent families. We identified TBC1D24
      mutations in 11 individuals from nine families (by exome sequencing in seven
      families, and Sanger sequencing in two families). 18 families had individuals
      with all five main features of DOORS syndrome, and TBC1D24 mutations were
      identified in half of these families. The seizure types in individuals with
      TBC1D24 mutations included generalised tonic-clonic, complex partial, focal
      clonic, and infantile spasms. Of the 18 individuals with DOORS syndrome from 17
      families without TBC1D24 mutations, eight did not have seizures and three did not
      have deafness. In expression studies, some mutations abrogated TBC1D24 mRNA
      stability. We also detected Tbc1d24 expression in mouse phalangeal chondrocytes
      and calvaria, which suggests a role of TBC1D24 in skeletogenesis. INTERPRETATION:
      Our findings suggest that mutations in TBC1D24 seem to be an important cause of
      DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS
      syndrome without deafness and seizures but with the other features should still
      be screened for TBC1D24 mutations. More information is needed to understand the
      cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes
      in individuals who do not have a mutation in TBC1D24. FUNDING: US National
      Institutes of Health, the CIHR (Canada), the NIHR (UK), the Wellcome Trust, the
      Henry Smith Charity, and Action Medical Research.

PMID- 24291223
TI  - Genetic ablation and short-duration inhibition of lipoxygenase results in
      increased macroautophagy.
AB  - 12/15-lipoxygenase (12/15-LOX) is involved in organelle homeostasis by degrading
      mitochondria in maturing red blood cells and by eliminating excess peroxisomes in
      liver. Furthermore, 12/15-LOX contributes to diseases by exacerbating oxidative
      stress-related injury, notably in stroke. Nonetheless, it is unclear what the
      consequences are of abolishing 12/15-LOX activity. Mice in which the alox15 gene
      has been ablated do not show an obvious phenotype, and LOX enzyme inhibition is
      not overtly detrimental. We show here that liver histology is also unremarkable.
      However, electron microscopy demonstrated that 12/15-LOX knockout surprisingly
      leads to increased macroautophagy in the liver. Not only macroautophagy but also
      mitophagy and pexophagy were increased in hepatocytes, which otherwise showed
      unaltered fine structure and organelle morphology. These findings were
      substantiated by immunofluorescence showing significantly increased number of LC3
      puncta and by Western blotting demonstrating a significant increase for LC3-II
      protein in both liver and brain homogenates of 12/15-LOX knockout mice.
      Inhibition of 12/15-LOX activity by treatment with four structurally different
      inhibitors had similar effects in cultured HepG2 hepatoma cells and SH-SY5Y
      neuroblastoma cells with significantly increased autophagy discernable already
      after 2 hours. Hence, our study reveals a link between ablation or inhibition of
      12/15-LOX and stimulation of macroautophagy. The enhanced macroautophagy may be
      related to the known tissue-protective effects of LOX ablation or inhibition
      under various diseased conditions caused by oxidative stress and ischemia. This
      could provide an important cleaning mechanism of cells and tissues to prevent
      accumulation of damaged mitochondria and other cellular components. 

PMID- 24291224
TI  - Discordance of IGF-1 and GH stimulation testing for altered GH secretion in
      obesity.
AB  - OBJECTIVE: To investigate the concordance/discordance of IGF-1 and peak
      stimulated GH in identifying subjects with reduced GH secretion and to determine
      the physiological significance of any discordance in obese subjects. DESIGN,
      PATIENTS AND METHODS: 95 obese and 43 normal weight men and women underwent
      measurement of IGF-1 and GH stimulation testing with GH releasing hormone (GHRH)
      arginine. Reduced IGF-1 and GH secretion were defined using pre-determined cut
      points. Cardiovascular disease risk was determined by measuring carotid intima
      media thickness (cIMT). In a second study, IGF-1 was measured in 52 obese men and
      women who underwent GH stimulation testing and overnight frequent blood sampling.
      The association of IGF-1 and peak stimulated GH with parameters of endogenous GH
      secretion was assessed. RESULTS: 60% of obese subjects had normal IGF-1 and peak
      stimulated GH while 8.4% of obese subjects had reduced IGF-1 and GH secretion.
      Discordance rate for IGF-1 and peak GH was 31.6%. Subjects with both low IGF-1
      and low peak GH had the highest cIMT, while subjects with both normal IGF-1 and
      peak GH had the lowest cIMT. Subjects with reduction in either IGF-1 or peak GH,
      had intermediate cIMT (P=0.02). IGF-1 and peak stimulated GH were associated with
      maximum and mean overnight serum GH and GH AUC as well as maximum peak mass and
      median pulse mass. Peak stimulated GH, but not IGF-1, was also associated with
      nadir overnight serum GH concentration and basal GH secretion. CONCLUSION: Peak
      stimulated GH and IGF-1 demonstrate significant discordance in identification of
      subjects with reduced GH secretion in obesity. Subjects with reduction of either
      IGF-1 or peak GH had higher cIMT compared to subjects with both normal IGF-1 and
      peak GH. Subjects with reductions in both IGF-1 and peak GH had the highest cIMT.
      Peak GH, compared to IGF-1, has broader associations with various parameters of
      endogenous GH secretion which support its utility in identifying those with
      reduced GH secretion.

PMID- 24291225
TI  - Genetic diversity of ORF3 and spike genes of porcine epidemic diarrhea virus in
      Thailand.
AB  - Porcine epidemic diarrhea virus (PEDV) has become endemic in the Thai swine
      industry, causing economic losses and repeated outbreaks since its first
      emergence in 2007. In the present study, 69 Thai PEDV isolates were obtained from
      50 swine herds across Thailand during the period 2008-2012. Both partial and
      complete nucleotide sequences of the spike (S) glycoprotein and the nucleotide
      sequences of ORF3 genes were determined to investigate the genetic diversity and
      molecular epidemiology of Thai PEDV. Based on the analysis of the partial S
      glycoprotein genes, the Thai PEDV isolates were clustered into 2 groups related
      to Korean and Chinese field isolates. The results for the complete spike genes,
      however, demonstrated that both groups were grouped in the same cluster.
      Interestingly, both groups of Thai PEDV isolates had a 4-aa (GENQ) insertion
      between positions 55 and 56, a 1-aa insertion between positions 135 and 136, and
      a 2-aa deletion between positions 155 and 156, making them identical to the
      Korean KNU series and isolates responsible for outbreaks in China in recent
      years. In addition to the complete S sequences, the ORF3 gene analyses suggested
      that the isolates responsible for outbreaks in Thailand are not vaccine related.
      The results of this study suggest that the PEDV isolates responsible for
      outbreaks in Thailand since its emergence represent a variant of PEDV that was
      previously reported in China and Korea. 

PMID- 24291227
TI  - The importance of regulatory RNAs in Staphylococcus aureus.
AB  - RNA molecules with regulatory functions in pathogenic bacteria have benefited
      from a renewed interest these two last decades. In Staphylococcus aureus, recent
      genome-wide approaches have led to the discovery that almost 10-20% of genes code
      for RNAs with critical regulatory roles in adaptive processes. These RNAs include
      trans-acting RNAs, which mostly act through binding to target mRNAs, and cis
      acting RNAs, which include regulatory regions of mRNAs responding to various
      metabolic signals. Besides recent analysis of S. aureus transcriptome has
      revealed an unprecedented existence of pervasive transcription generating a high
      number of weakly expressed antisense RNAs along the genome as well as numerous
      mRNAs with overlapped regions. Here, we will illustrate the diversity of trans
      acting RNAs and illustrate how they are integrated into complex regulatory
      circuits, which link metabolism, stress response and virulence. 

PMID- 24291228
TI  - Genomic diversity of human papillomaviruses (HPV) and clinical implications: an
      overview in adulthood and childhood.
AB  - During the last years, several researchers have highlighted the importance of
      characterizing more than one genomic region in order to detect recombination and
      classify variants of human papillomaviruses (HPVs) properly. HPVs variants differ
      in their biological, molecular and chemical properties. Therefore, this genomic
      diversity can present differences in the natural history and pathogenicity of
      HPVs. Different 'high-risk' HPVs variants of the genotypes HPV 16 and 18 can
      confer varied risks of viral persistence in the human cervix and influence HPVs
      progression to cervical cancer. Moreover, different 'low-risk' HPVs variants of
      the genotypes HPV 6 and 11 can play a unique role in the development of
      anogenital and cutaneous warts, recurrent respiratory papillomatosis (RRP) and
      ophthalmic pterygium. In future, the precise impact of genomic HPVs diversity to
      the clinical course of HPVs-associated diseases as well as to the efficacy of the
      current HPVs vaccines remains to be elucidated. 

PMID- 24291229
TI  - Sleep experiences, dissociation, imaginal experiences, and schizotypy: the role
      of context.
AB  - Watson (2001) reported moderate correlations between the Iowa Sleep Experience
      Survey (ISES) and self-report measures of dissociation and schizotypy. Subsequent
      investigations (Fassler, Knox, & Lynn, 2003; Watson, 2003) reported similar,
      although somewhat more modest, correlations between the ISES and measures of
      dissociation and schizotypy, as well as with measures of absorption and negative
      affect. The present study tested subjects in conditions in which the measures of
      sleep experiences were administered with other measures in either the same (N=86)
      or a different (N=87) test context. We determined that sleep experiences were
      associated with measures of dissociation, absorption, and schizotypy. We closely
      replicated Watson (2001) and found that the ISES correlations with other measures
      were not affected by the test context. We suggest that Watson's (2001)
      hypothesized common domain of unusual cognitive and perceptual experiences (e.g.,
      sleep experiences) may be underpinned by common ties to imaginative experiences. 

PMID- 24291226
TI  - Comparative genomics of oral isolates of Streptococcus mutans by in silico genome
      subtraction does not reveal accessory DNA associated with severe early childhood
      caries.
AB  - Comparative genomics is a popular method for the identification of microbial
      virulence determinants, especially since the sequencing of a large number of
      whole bacterial genomes from pathogenic and non-pathogenic strains has become
      relatively inexpensive. The bioinformatics pipelines for comparative genomics
      usually include gene prediction and annotation and can require significant
      computer power. To circumvent this, we developed a rapid method for genome-scale
      in silico subtractive hybridization, based on blastn and independent of feature
      identification and annotation. Whole genome comparisons by in silico genome
      subtraction were performed to identify genetic loci specific to Streptococcus
      mutans strains associated with severe early childhood caries (S-ECC), compared to
      strains isolated from caries-free (CF) children. The genome similarity of the 20
      S. mutans strains included in this study, calculated by Simrank k-mer sharing,
      ranged from 79.5% to 90.9%, confirming this is a genetically heterogeneous group
      of strains. We identified strain-specific genetic elements in 19 strains, with
      sizes ranging from 200 to 39 kb. These elements contained protein-coding regions
      with functions mostly associated with mobile DNA. We did not, however, identify
      any genetic loci consistently associated with dental caries, i.e., shared by all
      the S-ECC strains and absent in the CF strains. Conversely, we did not identify
      any genetic loci specific with the healthy group. Comparison of previously
      published genomes from pathogenic and carriage strains of Neisseria meningitidis
      with our in silico genome subtraction yielded the same set of genes specific to
      the pathogenic strains, thus validating our method. Our results suggest that S.
      mutans strains derived from caries active or caries free dentitions cannot be
      differentiated based on the presence or absence of specific genetic elements. Our
      in silico genome subtraction method is available as the Microbial Genome
      Comparison (MGC) tool, with a user-friendly JAVA graphical interface.

PMID- 24291230
TI  - Patella denervation in primary total knee arthroplasty - a randomized controlled
      trial with 2 years of follow-up.
AB  - We randomized 126 consecutive patients undergoing primary total knee arthroplasty
      into group 1: patella denervation (n = 63) and group 2: no patella denervation (n
      = 63). Assessment was performed preoperatively and at 3, 12 and 24 months post
      operatively. Average follow-up of patients was 26.5 months for denervation group
      and 26.3 months for no denervation group (P = 0.84). Pain scores for anterior
      knee pain were significantly better in the denervation group at 3 months but not
      at 12 and 24 months. Patient satisfaction was higher in the denervation group.
      Flexion range was higher in the denervation group at 3, 12 and 24 months review
      (P < 0.01). There were, however, no statistically significant differences with
      other validated knee scores.

PMID- 24291231
TI  - Hypoxic preconditioning-induced mitochondrial protection is not disrupted in a
      cell model of mtDNA T8993G mutation-induced F1F0-ATP synthase defect: the role of
      mitochondrial permeability transition.
AB  - Transient opening of the mitochondrial permeability transition pore plays a
      crucial role in hypoxic preconditioning-induced protection. Recently, the
      cyclophilin-D component of the mitochondrial permeability transition pore has
      been shown to interact with and regulate the F1F0-ATP synthase. However, the
      precise role of the F1F0-ATP synthase and the interaction between cyclophilin-D
      and F1F0-ATP synthase in the mitochondrial permeability transition pore and
      hypoxic preconditioning remain uncertain. Here we found that a 1-h hypoxic
      preconditioning delayed apoptosis and improved cell survival after stimulation
      with various apoptotic inducers including H2O2, ionomycin, and arachidonic acid
      in mitochondrial DNA T8993G mutation (NARP) osteosarcoma 143B cybrids, an F1F0
      ATP synthase defect cell model. This hypoxic preconditioning protected NARP
      cybrid cells against focal laser irradiation-induced oxidative stress by
      suppressing reactive oxygen species formation and preventing the depletion of
      cardiolipin. Furthermore, the protective functions of transient opening of the
      mitochondrial permeability transition pore in both NARP cybrids and wild-type
      143B cells can be augmented by hypoxic preconditioning. Disruption of the
      interaction between cyclophilin-D and F1F0-ATP synthase by cyclosporin A
      attenuated the mitochondrial protection induced by hypoxic preconditioning in
      both NARP cybrids and wild-type 143B cells. Our results demonstrate that the
      interaction between cyclophilin-D and F1F0-ATP synthase is important in the
      hypoxic preconditioning-induced cell protection. This finding improves our
      understanding of the mechanism of mitochondrial permeability transition pore
      opening in cells in response to hypoxic preconditioning, and will be helpful in
      further developing new pharmacological agents targeting hypoxia-reoxygenation
      injury and mitochondria-mediated cell death. 

PMID- 24291232
TI  - beta-Catenin, a Sox2 binding partner, regulates the DNA binding and
      transcriptional activity of Sox2 in breast cancer cells.
AB  - Sox2, an embryonic stem cell marker, has been recently implicated in the
      pathogenesis of breast cancer (BC). Using liquid chromatography-mass spectrometry
      and co-immunoprecipitation, we identified beta-catenin as a Sox2 binding partner
      in MCF7 cells. The interaction between Sox2 and beta-catenin was substantially
      different between the two cell subsets separated based on their differential
      responsiveness to a Sox2 reporter. Specifically, while beta-catenin binds to Sox2
      in the nuclear fraction of cells showing reporter-responsiveness (i.e. RR cells),
      this interaction was not detectable in those that were reporter-unresponsive
      (i.e. RU cells). In RR but not in RU cells, siRNA knockdown of beta-catenin
      significantly upregulated the Sox2 transcriptional activity, enhanced its DNA
      binding and increased the expression of its target genes. Correlating with these
      findings, while inhibition of beta-catenin significantly downregulated the
      mammosphere formation efficiency in RU cells, this treatment paradoxically
      increased that of RR cells. To conclude, we identified that beta-catenin is an
      important binding partner of Sox2 and a regulator of its transcriptional activity
      in a small subset of BC cells. The interaction between Sox2 and beta-catenin
      provides a novel mechanism underlying the functional dichotomy of BC cells, which
      carries potential therapeutic implications. 

PMID- 24291233
TI  - Prediction of posttranslational modification sites from amino acid sequences with
      kernel methods.
AB  - Post-translational modification (PTM) is the chemical modification of a protein
      after its translation and one of the later steps in protein biosynthesis for many
      proteins. It plays an important role which modifies the end product of gene
      expression and contributes to biological processes and diseased conditions.
      However, the experimental methods for identifying PTM sites are both costly and
      time-consuming. Hence computational methods are highly desired. In this work, a
      novel encoding method PSPM (position-specific propensity matrices) is developed.
      Then a support vector machine (SVM) with the kernel matrix computed by PSPM is
      applied to predict the PTM sites. The experimental results indicate that the
      performance of new method is better or comparable with the existing methods.
      Therefore, the new method is a useful computational resource for the
      identification of PTM sites. A unified standalone software PTMPred is developed.
      It can be used to predict all types of PTM sites if the user provides the
      training datasets. The software can be freely downloaded from
      http://www.aporc.org/doc/wiki/PTMPred. 

PMID- 24291234
TI  - Arsenic is cytotoxic and genotoxic to primary human lung cells.
AB  - Arsenic originates from both geochemical and numerous anthropogenic activities.
      Exposure of the general public to significant levels of arsenic is widespread.
      Arsenic is a well-documented human carcinogen. Long-term exposure to high levels
      of arsenic in drinking water has been linked to bladder, lung, kidney, liver,
      prostate, and skin cancers. Among them, lung cancer is of great public concern.
      However, little is known about how arsenic causes lung cancer and few studies
      have considered effects in normal human lung cells. The purpose of this study was
      to determine the cytotoxicity and genotoxicity of arsenic in human primary
      bronchial fibroblast and epithelial cells. Our data show that arsenic induces a
      concentration-dependent decrease in cell survival after short (24h) or long
      (120h) exposures. Arsenic induces concentration-dependent but not time-dependent
      increases in chromosome damage in fibroblasts. No chromosome damage is induced
      after either 24h or 120h arsenic exposure in epithelial cells. Using neutral
      comet assay and gamma-H2A.X foci forming assay, we found that 24h or 120h
      exposure to arsenic induces increases in DNA double strand breaks in both cell
      lines. These data indicate that arsenic is cytotoxic and genotoxic to human lung
      primary cells but lung fibroblasts are more sensitive to arsenic than epithelial
      cells. Further research is needed to understand the specific mechanisms involved
      in arsenic-induced genotoxicity in human lung cells. 

PMID- 24291235
TI  - Mesenchymal to epithelial transition in sarcomas.
AB  - Mesenchymal to epithelial transition (MET) in carcinomas has been proposed to
      promote the growth of epithelial tumour cells at distant sites during metastasis.
      MET has also been suggested as an important biological and clinical process in
      mesenchymal tumors, sarcomas. Here we review studies on MET in sarcomas,
      including molecular markers, signalling mechanisms, regulation by micro RNAs and
      therapeutic implications. Accumulating evidences suggest that deeper
      investigation and understanding of MET in sarcomas would shed light on the
      pathogenesis of sarcomas and might lead to identification of potential clinical
      biomarkers for prognosis and targets for sarcoma therapeutics. 

PMID- 24291237
TI  - Estimating mental workload through event-related fluctuations of pupil area
      during a task in a virtual world.
AB  - Monitoring mental load for optimal performance has become increasingly central
      with the recently evolving need to cope with exponentially increasing amounts of
      data. This paper describes a non-intrusive, objective method to estimate mental
      workload in an immersive virtual reality system, through analysis of frequencies
      of pupil fluctuations. We tested changes in mental workload with a number of task
      repetitions, level of predictability of the task and the effect of prior
      experience in predictable task performance, on mental workload of unpredictable
      task performance. Two measures were used to calculate mental workload: the ratio
      of Low Frequency to High Frequency components of pupil fluctuations, and the High
      Frequency alone, all extracted from the Power Spectrum Density of pupil
      fluctuations. Results show that mental workload decreases with a number of
      repetitions, creating a mode in which the brain acts as an automatic controller.
      Automaticity during training occurs only after a minimal number of repetitions,
      which once achieved, resulted in further improvements in the performance of
      unpredictable motor tasks, following training in a predictable task. These
      results indicate that automaticity is a central component in the transfer of
      skills from highly predictable to low predictable motor tasks. Our results
      suggest a potentially applicable method to brain-computer-interface systems that
      adapt to human mental workload, and provide intelligent automated support for
      enhanced performance. 

PMID- 24291238
TI  - Ethical considerations regarding early liver transplantation in patients with
      severe alcoholic hepatitis not responding to medical therapy.
AB  - A recent study proposed that liver transplantation may represent life-saving
      treatment in patients with severe alcoholic hepatitis not responding to medical
      therapy. In this pilot experience, stringent patient selection resulted in major
      improvement of short-term survival with low rates of post-transplant alcohol
      relapse. In the context of organ shortage, which imposes a need for strict
      selection of transplant candidates, these results raise major ethical questions.
      Reluctance to perform liver transplantation in alcoholics is based on the fact
      that alcoholism is frequently considered to be self-inflicted and on fears of
      harmful post-transplant alcoholism recurrence. A minimal interval of sobriety
      lasting at least 6 months is a widely adopted criterion for the selection of
      patients with alcoholic liver disease for liver transplantation. In severe
      alcoholic hepatitis, the disastrous short-term prognosis in patients not
      responding to medical therapy does not allow one to reasonably impose an
      arbitrary period of 6-months of abstinence. This means that these patients must
      be either systematically excluded from transplantation or selected according to
      other criteria. Without significant pre-transplant abstinence, it might be argued
      that these patients do not merit a graft as they have not demonstrated their
      ability to gain control over their disease through durable modification of their
      behaviour. Consequently, this procedure could have a negative impact in the
      public, affecting organ donation and confidence in the fairness of transplant
      programs. In contrast, ethical principles recommend active treatment of patients,
      without discrimination, according to the best scientific knowledge. At this
      stage, we propose that there are no major ethical barriers for further evaluation
      of this new therapeutic option. The next steps should include transparent
      communication with the public and further studies to reproduce these results and
      identify the selection criteria that provide the best long-term outcomes.

PMID- 24291239
TI  - Extended duration therapy with pegylated interferon and ribavirin for patients
      with genotype 3 hepatitis C and advanced fibrosis: final results from the STEPS
      trial.
AB  - BACKGROUND & AIMS: Patients with genotype 3 hepatitis C virus (HCV) infection and
      cirrhosis have poor response rates after 24 weeks treatment with pegylated
      interferon and ribavirin. Treatment for 48 weeks is therefore recommended,
      although the benefits of this are untested. We examined extended therapy in
      patients with genotype 3 HCV and advanced fibrosis. METHODS: Multicentre, open
      labelled randomized trial comparing therapy with 24 weeks pegylated interferon
      and ribavirin to 48 weeks of the same therapy. RESULTS: 136 patients completed
      the study. 67 received 24 weeks therapy and the SVR rate (48%) did not differ
      from that seen in the 69 patients who received 48 weeks therapy (42%). The
      response rates in patients with biopsy proven cirrhosis (13 patients treated for
      24 weeks, 18 patients treated for 48 weeks) or cirrhosis proven on imaging (28
      patients treated for 24 weeks and 25 patients treated for 48 weeks) were 46% in
      those treated for 24 weeks and 40% in those treated for 48 weeks. The differences
      were not significantly different. Treatment failure was due to relapse in the
      majority of patients. CONCLUSIONS: Patients with genotype 3 HCV and advanced
      fibrosis do not benefit from extended therapy with pegylated interferon and
      ribavirin.

PMID- 24291236
TI  - Ribosomal S6 kinase regulates ischemia-induced progenitor cell proliferation in
      the adult mouse hippocampus.
AB  - Ischemia-induced progenitor cell proliferation is a prominent example of the
      adult mammalian brain's ability to regenerate injured tissue resulting from
      pathophysiological processes. In order to better understand and exploit the cell
      signaling mechanisms that regulate ischemia-induced proliferation, we examined
      the role of the p42/44 mitogen-activated protein kinase (MAPK) cascade effector
      ribosomal S6 kinase (RSK) in this process. Here, using the endothelin-1 ischemia
      model in wild type mice, we show that the activated form of RSK is expressed in
      the progenitor cells of the subgranular zone (SGZ) after intrahippocampal
      cerebral ischemia. Further, RSK inhibition significantly reduces ischemia-induced
      SGZ progenitor cell proliferation. Using the neurosphere assay, we also show that
      both SGZ- and subventricular zone (SVZ)-derived adult neural stem cells (NSC)
      exhibit a significant reduction in proliferation in the presence of RSK and MAPK
      inhibitors. Taken together, these data reveal RSK as a regulator of ischemia
      induced progenitor cell proliferation, and as such, suggest potential therapeutic
      value may be gained by specifically targeting the regulation of RSK in the
      progenitor cell population of the SGZ. 

PMID- 24291240
TI  - Staging chronic hepatitis C in seven categories using fibrosis biomarker
      (FibroTestTM) and transient elastography (FibroScan(r)).
AB  - BACKGROUND & AIMS: FibroTestTM (FT) and Transient Elastography (TE) have been
      validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using
      biopsy, and as prognostic markers of liver related mortality in patients with
      chronic hepatitis C. The aim was to extend the validation of FT and TE as markers
      of critical steps defined by occurrence of cirrhosis without complications
      (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver
      cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or
      jaundice). METHODS: The updated individual data of 3927 patients (1046
      cirrhotics) without complications at baseline were pooled from three prospective
      cohorts called "EPIC", "Paris", and "Bordeaux" cohorts. RESULTS: At 5 years,
      among 501 patients without varices at baseline (F4.1) varices occurred in 19
      patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance
      (AUROC) of FT was 0.77 (0.66-0.84; p<0.001). At 10 years severe complications
      occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary
      liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on
      treatment) of severe complications [AUROC 0.79 (76-82); p<0.0001], including
      primary liver cancer [AUROC 0.84 (80-87); p<0.0001]. Similarly TE was predictive
      of severe complications [AUROC 0.77 (72-81); p<0.0001], including primary liver
      cancer [AUROC 0.86 (81-90); p<0.0001]. CONCLUSIONS: FibroTestTM and TE increase
      were associated with the occurrence of all severe complications including
      hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding.
      FibroTestTM increase was also associated with the occurrence of esophageal
      varices.

PMID- 24291242
TI  - Risk of diabetes and cardiovascular disease in patients with primary sclerosing
      cholangitis.
AB  - BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is associated with
      increased mortality. Cardiovascular disease is a leading cause of death in the
      Western world. We examined the risk of cardiovascular disease and diabetes (type
      1 and type 2) in patients with PSC and their first-degree relatives. METHODS:
      This prospective multicentre cohort study included 678 individuals with PSC
      diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched
      for age, and sex. Through linkage of the Swedish Multigeneration Register we
      identified 3139 first-degree relatives to PSC patients and 30,953 first-degree
      relatives to the matched comparison cohort. We retrieved data on cardiovascular
      disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient
      Register, and then examined the association with PSC or having a family history
      of PSC using Poisson regression. RESULTS: During 125,127 person-years of follow
      up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This
      corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular
      disease in individuals with PSC (95% CI=2.86-3.91). The highest risk estimates
      were seen for diseases of the arteries, veins, and lymphatic vessels while the RR
      was neutral for ischemic heart disease (0.90) or only slightly elevated for
      cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no
      increased risk of cardiovascular disease (RR=0.87; 95% CI=0.80-0.95). Individuals
      with PSC (RR=7.95; 95% CI=4.82-13.12), and to some extent also their first-degree
      relatives (RR=1.73; 95% CI=1.19-2.52) were at increased risk of T1D. Also for T2D
      were the RR is higher in individuals with PSC (RR=2.54; 95% CI=1.56-4.13) than in
      PSC first-degree relatives (RR=0.81; 95% CI=0.65-1.02). CONCLUSIONS: PSC was
      associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast,
      first-degree relatives to PSC patients were only at a moderately increased risk
      of T1D, and at no increased risk of either cardiovascular disease or T2D.

PMID- 24291241
TI  - Non-alcoholic fatty liver disease: spectral patterns observed from an in vivo
      phosphorus magnetic resonance spectroscopy study.
AB  - BACKGROUND & AIMS: Liver biopsy is the gold standard for diagnosing non-alcoholic
      fatty liver disease (NAFLD) but with practical constraints. Phosphorus magnetic
      resonance spectroscopy ((31)P-MRS) allows in vivo assessment of hepatocellular
      metabolism and has shown potential for biochemical differentiation in diffuse
      liver disease. Our aims were to describe spectroscopic signatures in biopsy
      proven NAFLD and to determine diagnostic performance of (31)P-MRS for non
      alcoholic steatohepatitis (NASH). METHODS: (31)P-MRS was performed in 151
      subjects, comprised of healthy controls (n=19) and NAFLD patients with non-NASH
      (n=37) and NASH (n=95). Signal intensity ratios for phosphomonoesters (PME)
      including phosphoethanolamine (PE), phosphodiesters (PDE) including
      glycerophosphocholine (GPC), total nucleotide triphosphate (NTP) including alpha
      NTP, and inorganic phosphate (Pi), expressed relative to total phosphate (TP) or
      [PME+PDE] and converted to percentage, were obtained. RESULTS: Compared to
      controls, both NAFLD groups had increased PDE/TP (p<0.001) and decreased Pi/TP
      (p=0.011). Non-NASH patients showed decreased PE/[PME+PDE] (p=0.048), increased
      GPC/[PME+PDE] (p<0.001), and normal NTP/TP and alpha-NTP/TP. Whereas, NASH
      patients had normal PE/[PME+PDE] and GPC/[PME+PDE], but decreased NTP/TP
      (p=0.004) and alpha-NTP/TP (p<0.001). The latter was significantly different
      between non-NASH and NASH (p=0.047) and selected as discriminating parameter,
      with area under the receiver-operating characteristics curve of 0.71 (95%
      confidence interval, 0.62-0.79). An alpha-NTP/TP cutoff of 16.36% gave 91%
      sensitivity and cutoff of 10.57% gave 91% specificity for NASH. CONCLUSIONS:
      (31)P-MRS shows distinct biochemical changes in different NAFLD states, and has
      fair diagnostic accuracy for NASH.

PMID- 24291243
TI  - Jellyfish collagen stimulates production of TNF-alpha and IL-6 by J774.1 cells
      through activation of NF-kappaB and JNK via TLR4 signaling pathway.
AB  - We previously reported that jellyfish collagen stimulates both the acquired and
      innate immune responses. In the acquired immune response, jellyfish collagen
      enhanced immunoglobulin production by lymphocytes in vitro and in vivo.
      Meanwhile, in the innate immune response jellyfish collagen promoted cytokine
      production and phagocytotic activity of macrophages. The facts that jellyfish
      collagen plays several potential roles in stimulating cytokine production by
      macrophages have further attracted us to uncover its mechanisms. We herein
      describe that the cytokine production-stimulating activity of jellyfish collagen
      was canceled by a Toll-like receptor 4 (TLR4) inhibitor. Moreover, jellyfish
      collagen stimulated phosphorylation of inhibitor of kappaBalpha (IkappaBalpha),
      promoted the translocation of nucleus factor-kappaB (NF-kappaB), and activated c
      Jun N-terminal kinase (JNK). A JNK inhibitor also abrogated the cytokine
      production-stimulating activity of jellyfish collagen. These results suggest that
      jellyfish collagen may facilitate cytokine production by macrophages through
      activation of NF-kappaB and JNK via the TLR4 signaling pathways. 

PMID- 24291244
TI  - Active demethylation of the IL-2 Promoter in CD4+ T cells is mediated by an
      inducible DNA glycosylase, Myh.
AB  - Epigenetic control of tissue-specific gene expression is often achieved by active
      demethylation of promoter regions; however, the nature of all the enzymes
      mediating this remodeling process is not fully clear. Here we describe a 5
      methylcytosine glycosylase activity for the murine DNA base excision repair
      enzyme Myh and show that it is critically involved in remodeling the IL-2
      Promoter for transcription. The enzyme is not expressed in naive CD4(+) T cells,
      but can be transiently induced following T cell activation. T cells deficient in
      Myh had blunted demethylation of the promoter and impaired IL-2 secretion but not
      IFN-gamma. An in vitro assay for the glycosylase activity revealed the enzyme to
      be sequence specific for certain CpG sites in the IL-2 Promoter. These results
      suggest that DNA demethylation is being selectively used to orchestrate a part of
      the naive CD4(+) T cell differentiation program. 

PMID- 24291245
TI  - The temporary dynamics of inflammation-related genes expression under tuftsin
      analog Selank action.
AB  - Previous studies have shown that synthetic tuftsin analogue Selank and its
      fragments cause a number of alterations in the expression of certain genes
      involved in inflammation in mouse spleen. In this work we studied the effect of
      Selank and its short fragment Gly-Pro on the temporary dynamics of C3, Casp1,
      Il2rg, and Xcr1 genes expression in mouse spleen after single intraperitoneal
      injection (100 MUg/kg) of peptides using real-time PCR method. We found a
      significant 3-fold decrease in the C3 mRNA level just 30 min after Selank
      injection and similar alteration this gene mRNA level after Gly-Pro
      administration. A wave-like alteration in the Casp1 mRNA level was observed after
      Selank injection. We found a significant alteration in the mRNA level of the
      Il2rg gene at early time points after Selank and Gly-Pro administration and an
      almost equal reduction in the Xcr1 mRNA level 90 min after the administration of
      Selank and its fragment. Our results showed that, Selank and its short fragment
      Gly-Pro influence the expression of genes that mediate different types of immune
      responses, thereby maintaining the balance of the immune system. It should be
      noted that in most cases, there was a coincidence in the expression profiles of
      the studied genes after Selank and Gly-Pro administration. This might indicate an
      active contribution of the dipeptide to the final effect of Selank.

PMID- 24291246
TI  - The division of visual attention affects the transition point from level walking
      to stair descent in healthy, active older adults.
AB  - BACKGROUND: Stair descent is a frequent daily activity that poses great risks for
      injury due to falling. Very little is understood about the attentional demands of
      stair descent and their changes with aging. The present study compared combined
      locomotor and cognitive functioning during different phases of stair descent
      between healthy young and older individuals. METHODS: Sixteen young and sixteen
      healthy older subjects walked down a 5-step staircase, performing a simultaneous
      visual Stroop task (i.e., a dual task) during the approach, transition or steady
      state descent phases in some trials. Three dimensional kinematics of trunk and
      foot motion were recorded along with the accuracy and dual task costs (DTCs) for
      responses to the Stroop stimuli. RESULTS: Dual tasking influenced both gait and
      cognitive performance for all subjects, and older adults generally walked slower
      with higher foot clearances and had greater DTCs. Specific age differences were
      found at stair transition where older adults showed more attentional effects.
      CONCLUSIONS: Healthy, active older adults showed changes to attention and
      planning due to normal aging specifically associated with a crucial point of fall
      risk during stair descent.

PMID- 24291247
TI  - Combination of N-acetylcysteine, alpha-lipoic acid and alpha-tocopherol
      substantially prevents the brain synaptosomal alterations and memory and learning
      deficits of aged rats.
AB  - This study has compared several synaptosomal parameters in three groups of rats:
      young (46 months), aged (22-24 months) and antioxidant supplemented aged rats
      (antioxidant supplementation given with the diet as a combination of N
      acetylcysteine, alpha-lipoic acid and alpha-tocopherol from 18 months onwards
      till 22-24 months). The synaptosomes from aged rat brain, in comparison to those
      of young animals, exhibit an increased membrane potential with altered contents
      of Na(+) and K(+) under basal incubation condition and in the presence of
      depolarizing agents. The intrasynaptosomal Ca(2+) is also higher in aged than in
      young rat. These age-dependent changes in synaptosomal parameters are prevented
      markedly in the antioxidant supplemented group. When examined on T-maze, the aged
      animals are noticeably impaired in learning and memory functions, but the deficit
      is remarkably prevented in the antioxidant supplemented aged animals. It is
      suggested that the synaptosomal alterations partly contribute to the cognitive
      deficits of aged animals, and both are rescued by long-term antioxidant
      supplementation.

PMID- 24291248
TI  - Digital photographic measurement in hypospadias: validation and comparison to
      intraoperative measurement.
AB  - BACKGROUND: We propose a standardized method of photographing the hypospadias
      penis to capture penile dimensions that may be relevant for surgery. We also
      validate the use of digital imaging software for calculating penile dimensions as
      a substitute for intraoperative caliper-based measurements. METHODS: Photographs
      were taken of hypospadias penises in four different views after placement of a
      traction stitch and retraction of the preputial hood. Intraoperative measurements
      were obtained with a caliper. Digital measurements were taken of the same
      parameters postoperatively. All measurements were obtained in triplicate by
      multiple participants, and averages were tested for equivalency by determining
      the correlation coefficient for each parameter. Inter-observer correlation was
      also calculated for each parameter. RESULTS: 180 intraoperative and 180 digital
      measurements were taken from 60 dimensions on 10 hypospadiac penises. Strong
      correlation existed between most digital and intraoperative measurements. Average
      inter-observer correlations ranged from 0.91 to 0.99 for each of the
      intraoperative measurements, and 0.90 to 1.00 for each of the digital
      measurements. CONCLUSIONS: Standardized imaging is effective in capturing penile
      dimensions and measurements during hypospadias surgery. When compared with
      intraoperative measurements, digital measurements are reliable and precise;
      digital photography has the potential to both aid in surgical planning and
      improve documentation.

PMID- 24291249
TI  - Short pelvic floor EMG lag time II: use in management and follow-up of children
      treated for detrusor overactivity.
AB  - OBJECTIVE: To determine utility of short pelvic floor electromyography (EMG) lag
      time in monitoring therapeutic response in children with idiopathic detrusor
      overactivity (DO) and quiet EMG during voiding (idiopathic detrusor overactivity
      disorder, IDOD). PATIENTS AND METHODS: 162 consecutive normal children (77M, 85F)
      diagnosed with IDOD and short EMG lag time were reviewed. All were treated with
      combined standard urotherapy and anticholinergics. Pre-treatment uroflow/EMG
      parameters were compared with on-treatment parameters. RESULTS: Median age at
      evaluation was 6.8 years and median EMG lag time was 0 s; 110 children had repeat
      uroflow/EMG studies while on anticholinergic therapy. With a median follow-up of
      18.7 months, mean EMG lag time increased from 0.7 to 2.2 s and % expected bladder
      capacity for age (EBC) increased from 0.68 to 0.98 (both p < 0.01). EMG lag time
      increased in all patients while on therapy and normalized in 83 patients (75%).
      CONCLUSION: A short EMG lag time on noninvasive uroflow/EMG in a patient with
      urgency can be a surrogate for urodynamics study (UDS) in diagnosing DO and
      objectively monitoring response to therapy. When effectively treated, children
      with DO have amelioration of their lower urinary tract symptoms (LUTS) and
      normalization of both EMG lag time and bladder capacity.

PMID- 24291250
TI  - Urethral advancement in hypospadias with a distal division of the corpus
      spongiosum: outcome in 158 cases.
AB  - OBJECTIVE: Outcome of urethral mobilization and advancement (Koff procedure) in
      hypospadias with a distal division of the corpus spongiosum and redo cases with
      distal urethral failure. MATERIALS AND METHODS: From January 1999 to November
      2012, 158 children with a distal hypospadias (115 primary cases and 43 redo
      cases) underwent surgical repair using the Koff technique with a median age at
      surgery of 21 months (range, 12-217 months). RESULTS: Mean follow-up was 19
      months (median, 14 months). Thirty patients (19%) presented with a complication
      (13.9% in primary cases and 32.5% in redo surgery) mostly at the beginning of our
      experience. Meatal stenosis was the most common one (3.5% in primary case, 6%
      overall). Ventral curvature (>10 degrees ), which is considered as a possible
      long-term iatrogenic complication of the Koff procedure, was not found in
      patients with fully grown penis except in one redo patient who had,
      retrospectively, an inadequate indication for this type of repair. Of 158
      patients, 33 reached the age of puberty (>14 years old) with a mean follow-up of
      34 months, only one presented with a significant ventral curvature. CONCLUSION:
      Urethral mobilization and advancement is a reasonable alternative for anterior
      hypospadias and distal fistula repair in selected cases. It has two major
      advantages compared to other techniques: it avoids any urethroplasty with non
      urethral tissue and eliminates dysplastic tissues located beyond the division of
      the corpus spongiosum, which may not grow at the same pace as the rest of the
      penis. Significant iatrogenic curvature in fully grown penis is not supported by
      this series.

PMID- 24291251
TI  - Spatio-temporal patterns of genetic change amongst populations of cassava Bemisia
      tabaci whiteflies driving virus pandemics in East and Central Africa.
AB  - The greatest current threat to cassava in sub-Saharan Africa, is the continued
      expansion of plant virus pandemics being driven by super-abundant populations of
      the whitefly vector, Bemisia tabaci. To track the association of putatively
      genetically distinct populations of B. tabaci with pandemics of cassava mosaic
      disease (CMD) and cassava brown streak disease (CBSD), a comprehensive region
      wide analysis examined the phylogenetic relationships and population genetics of
      642 B. tabaci adults sampled from cassava in six countries of East and Central
      Africa, between 1997 and 2010, using a mitochondrial DNA cytochrome oxidase I
      marker (780 bases). Eight phylogenetically distinct groups were identified,
      including one, designated herein as 'East Africa 1' (EA1), not previously
      described. The three most frequently occurring groups comprised >95% of all
      samples. Among these, the Sub-Saharan Africa 2 (SSA2) group diverged by c. 8%
      from two SSA1 sub-groups (SSA1-SG1 and SSA1-SG2), which themselves were 1.9%
      divergent. During the 14-year study period, the group associated with the CMD
      pandemic expansion shifted from SSA2 to SSA1-SG1. Population genetics analyses of
      SSA1, using Tajima's D, Fu's Fs and Rojas' R2 statistics confirmed a temporal
      transition in SSA1 populations from neutrally evolving at the outset, to rapidly
      expanding from 2000 to 2003, then back to populations more at equilibrium after
      2004. Based on available evidence, hybrid introgression appears to be the most
      parsimonious explanation for the switch from SSA2 to SSA1-SG1 in whitefly
      populations driving cassava virus pandemics in East and Central Africa. 

PMID- 24291252
TI  - Quantitative phosphoproteomic analysis of host responses in human lung epithelial
      (A549) cells during influenza virus infection.
AB  - The emergence of antiviral drug-resistant influenza viruses highlights the need
      for alternative therapeutic strategies. Elucidation of host factors required
      during virus infection provides information not only on the signaling pathways
      involved but also on the identification of novel drug targets. RNA interference
      screening method had been utilized by several studies to determine these host
      factors; however, proteomics data on influenza host factors are currently
      limited. In this study, quantitative phosphoproteomic analysis of human lung cell
      line (A549) infected with 2009 pandemic influenza virus A (H1N1) virus was
      performed. Phosphopeptides were enriched from tryptic digests of total protein of
      infected and mock-infected cells using a titania column on an automated
      purification system followed by iTRAQ labeling. Identification and quantitative
      analysis of iTRAQ-labeled phosphopeptides were performed using LC-MS/MS. We
      identified 366 phosphorylation sites on 283 proteins. Of these, we detected 43
      upregulated and 35 downregulated proteins during influenza virus infection. Gene
      ontology enrichment analysis showed that majority of the identified proteins are
      phosphoproteins involved in RNA processing, immune system process and response to
      infection. Host-virus interaction network analysis had identified 23 densely
      connected subnetworks. Of which, 13 subnetworks contained proteins with altered
      phosphorylation levels during by influenza virus infection. Our results will help
      to identify potential drug targets that can be pursued for influenza antiviral
      drug development. 

PMID- 24291253
TI  - Subcellular localization of bacteriophage PRD1 proteins in Escherichia coli.
AB  - Bacteria possess an intricate internal organization resembling that of the
      eukaryotes. The complexity is especially prominent at the bacterial cell poles,
      which are also known to be the preferable sites for some bacteriophages to
      infect. Bacteriophage PRD1 is a well-known model serving as an ideal system to
      study structures and functions of icosahedral internal membrane-containing
      viruses. Our aim was to analyze the localization and interactions of individual
      PRD1 proteins in its native host Escherichia coli. This was accomplished by
      constructing a vector library for production of fluorescent fusion proteins.
      Analysis of solubility and multimericity of the fusion proteins, as well as their
      localization in living cells by confocal microscopy, indicated that multimeric
      PRD1 proteins were prone to localize in the cell poles. Furthermore, PRD1 spike
      complex proteins P5 and P31, as fusion proteins, were shown to be functional in
      the virion assembly. In addition, they were shown to co-localize in the specific
      polar area of the cells, which might have a role in the multimerization and
      formation of viral protein complexes. 

PMID- 24291254
TI  - Plasticity beyond peri-infarct cortex: spinal up regulation of structural
      plasticity, neurotrophins, and inflammatory cytokines during recovery from
      cortical stroke.
AB  - Stroke induces pathophysiological and adaptive processes in regions proximal and
      distal to the infarct. Recent studies suggest that plasticity at the level of the
      spinal cord may contribute to sensorimotor recovery after cortical stroke. Here,
      we compare the time course of heightened structural plasticity in the spinal cord
      against the temporal profile of cortical plasticity and spontaneous behavioral
      recovery. To examine the relation between trophic and inflammatory effectors and
      spinal structural plasticity, spinal expression of brain derived neurotrophic
      factor (BDNF), neurotrophin-3 (NT-3), tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-6 (IL-6) was measured. Growth-associated protein 43 (GAP-43),
      measured at 3, 7, 14, or 28 days after photothrombotic stroke of the forelimb
      sensorimotor cortex (FL-SMC) to provide an index of periods of heightened
      structural plasticity, varied as a function of lesion size and time after stroke
      in the cortical hemispheres and the spinal cord. Notably, GAP-43 levels in the
      cervical spinal cord were significantly increased after FL-SMC lesion, but the
      temporal window of elevated structural plasticity was more finite in spinal cord
      relative to ipsilesional cortical expression (returning to baseline levels by 28
      post-stroke). Peak GAP-43 expression in spinal cord occurred during periods of
      accelerated spontaneous recovery, as measured on the Montoya Staircase reaching
      task, and returned to baseline as recovery plateaued. Interestingly, spinal GAP
      43 levels were significantly correlated with spinal levels of the inflammatory
      cytokines TNF-alpha and IL-6 as well as the neurotrophin NT-3, while a transient
      increase in BDNF levels preceded elevated GAP-43 expression. These data identify
      a significant but time-limited window of heightened structural plasticity in the
      spinal cord following stroke that correlates with spontaneous recovery and the
      spinal expression of inflammatory cytokines and neurotrophic factors.

PMID- 24291255
TI  - Perinatal inflammation results in decreased oligodendrocyte numbers in adulthood.
AB  - AIMS: Maternal inflammation is a risk factor for preterm birth, and premature
      infants are often exposed to supplemental oxygen as a life-sustaining therapy.
      While more immature neonates are surviving, rates of neurodevelopmental
      impairment are not improving. We developed a novel mouse model with clinically
      relevant exposures to test the hypothesis that systemic maternal inflammation
      with transient neonatal hyperoxia exposure will induce a phenotype similar to
      diffuse periventricular leukomalacia (PVL) like that observed in premature human
      infants. MAIN METHODS: Timed-pregnant C3H/HeN mice received intraperitoneal
      injections of lipopolysaccharide (LPS) or saline on embryonic day 16. Newborn
      pups were placed in room air (RA) or 85% oxygen (O2) for 14 days, followed by 14
      days in RA recovery. Oligodendroglial and microglial populations were evaluated
      at 14 and 28 days. KEY FINDINGS: Brain weight to body weight ratios were lower in
      mice exposed to LPS. Oligodendrocyte numbers were decreased significantly in the
      cerebral cortex and hippocampus in groups exposed to LPS or LPS/O2 at 14 days,
      and persisted in the cerebral cortex at 28 days for LPS/O2 mice. At day 14,
      cleaved caspase 3 was increased and numbers of microglia were elevated in the
      cerebral cortex and hippocampus of LPS/O2 animals. SIGNIFICANCE: These data
      indicate that combining systemic maternal LPS and neonatal hyperoxic exposure
      impairs myelination, and suggests that this novel mouse model may represent a
      subtle, diffuse form of periventricular white matter injury that could provide a
      clinically relevant platform for further study of perinatal brain injury.

PMID- 24291256
TI  - Anthocyanins restore behavioral and biochemical changes caused by streptozotocin
      induced sporadic dementia of Alzheimer's type.
AB  - AIMS: The aim of this study was to analyze if the pre-administration of
      anthocyanin on memory and anxiety prevented the effects caused by
      intracerebroventricular streptozotocin (icv-STZ) administration-induced sporadic
      dementia of Alzheimer's type (SDAT) in rats. Moreover, we evaluated whether the
      levels of nitrite/nitrate (NOx), Na(+),K(+)-ATPase, Ca(2+)-ATPase and
      acethylcholinesterase (AChE) activities in the cerebral cortex (CC) and
      hippocampus (HC) are altered in this experimental SDAT. MAIN METHODS: Male Wistar
      rats were divided in 4 different groups: control (CTRL), anthocyanin (ANT),
      streptozotocin (STZ) and streptozotocin+anthocyanin (STZ+ANT). After seven days
      of treatment with ANT (200mg/kg; oral), the rats were icv-STZ injected (3mg/kg),
      and four days later the behavior parameters were performed and the animals
      submitted to euthanasia. KEY FINDINGS: A memory deficit was found in the STZ
      group, but ANT treatment showed that it prevents this impairment of memory
      (P<0.05). Our results showed a higher anxiety in the icv-STZ group, but treatment
      with ANT showed a per se effect and prevented the anxiogenic behavior induced by
      STZ. Our results reveal that the ANT treatment (100MUM) tested displaces the
      specific binding of [(3)H] flunitrazepam to the benzodiazepinic site of GABAA
      receptors. AChE, Ca(+)-ATPase activities and NOx levels were found to be
      increased in HC and CC in the STZ group, which was attenuated by ANT (P<0.05).
      STZ decreased Na(+),K(+)-ATPase activity and ANT was able to prevent these
      effects (P<0.05). SIGNIFICANCE: In conclusion, these findings demonstrated that
      ANT is able to regulate ion pump activity and cholinergic neurotransmission, as
      well as being able to enhance memory and act as an anxiolytic compound in animals
      with SDAT.

PMID- 24291258
TI  - Protein disulfide engineering.
AB  - Improving the stability of proteins is an important goal in many biomedical and
      industrial applications. A logical approach is to emulate stabilizing molecular
      interactions found in nature. Disulfide bonds are covalent interactions that
      provide substantial stability to many proteins and conform to well-defined
      geometric conformations, thus making them appealing candidates in protein
      engineering efforts. Disulfide engineering is the directed design of novel
      disulfide bonds into target proteins. This important biotechnological tool has
      achieved considerable success in a wide range of applications, yet the rules that
      govern the stabilizing effects of disulfide bonds are not fully characterized.
      Contrary to expectations, many designed disulfide bonds have resulted in
      decreased stability of the modified protein. We review progress in disulfide
      engineering, with an emphasis on the issue of stability and computational methods
      that facilitate engineering efforts. 

PMID- 24291257
TI  - Mass spectrometry for the biophysical characterization of therapeutic monoclonal
      antibodies.
AB  - Monoclonal antibodies (mAbs) are powerful therapeutics, and their
      characterization has drawn considerable attention and urgency. Unlike small
      molecule drugs (150-600 Da) that have rigid structures, mAbs (~150 kDa) are
      engineered proteins that undergo complicated folding and can exist in a number of
      low-energy structures, posing a challenge for traditional methods in structural
      biology. Mass spectrometry (MS)-based biophysical characterization approaches can
      provide structural information, bringing high sensitivity, fast turnaround, and
      small sample consumption. This review outlines various MS-based strategies for
      protein biophysical characterization and then reviews how these strategies
      provide structural information of mAbs at the protein level (intact or top-down
      approaches), peptide, and residue level (bottom-up approaches), affording
      information on higher order structure, aggregation, and the nature of antibody
      complexes.

PMID- 24291259
TI  - Therapeutic antibody engineering by high efficiency cell screening.
AB  - In recent years, several cell-based screening technologies for the isolation of
      antibodies with prescribed properties emerged. They rely on the multi-copy
      display of antibodies or antibody fragments on a cell surface in functional form
      followed by high through put screening and isolation of cell clones that carry an
      antibody variant with the desired affinity, specificity, and stability.
      Particularly yeast surface display in combination with high-throughput
      fluorescence-activated cell sorting has proven successful in the last fifteen
      years as a very powerful technology that has some advantages over classical
      generation of monoclonals using the hybridoma technology or bacteriophage-based
      antibody display and screening. Cell-based screening harbours the benefit of
      single-cell online and real-time analysis and characterisation of individual
      library candidates. Moreover, when using eukaryotic expression hosts, intrinsic
      quality control machineries for proper protein folding and stability exist that
      allow for co-selection of high-level expression and stability simultaneously to
      the binding functionality. Recently, promising technologies emerged that directly
      rely on antibody display on higher eukaryotic cell lines using lentiviral
      transfection or direct screening on B-cells. The combination of immunisation, B
      cell screening and next generation sequencing may open new avenues for the
      isolation of therapeutic antibodies with prescribed physicochemical and
      functional characteristics. 

PMID- 24291260
TI  - Src regulates membrane trafficking of the Kv3.1b channel.
AB  - The Kv3.1 channel plays a crucial role in regulating the high-frequency firing
      properties of neurons. Here, we determined whether Src regulates the subcellular
      distributions of the Kv3.1b channel. Co-expression of active Src induced a
      dramatic redistribution of Kv3.1b to the endoplasmic reticulum. Furthermore, co
      expression of the Kv3.1b channel with active Src induced a remarkable decrease in
      the pool of Kv3.1b at the cell surface. Moreover, the co-expression of active Src
      results in a significant decrease in the peak current densities of the Kv3.1b
      channel, and a substantial alteration in the voltage dependence of its steady
      state inactivation. Taken together, these results indicate that Src kinase may
      play an important role in regulating membrane trafficking of Kv3.1b channels. 

PMID- 24291261
TI  - An oxalyl-CoA synthetase is important for oxalate metabolism in Saccharomyces
      cerevisiae.
AB  - Although oxalic acid is common in nature our understanding of the mechanism(s)
      regulating its turnover remains incomplete. In this study we identify
      Saccharomyces cerevisiae acyl-activating enzyme 3 (ScAAE3) as an enzyme capable
      of catalyzing the conversion of oxalate to oxalyl-CoA. Based on our findings we
      propose that ScAAE3 catalyzes the first step in a novel pathway of oxalate
      degradation to protect the cell against the harmful effects of oxalate derived
      from an endogenous process or an environmental source. 

PMID- 24291262
TI  - Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion
      bodies.
AB  - Neurodegenerative disorders such as Huntington's disease are hallmarked by
      neuronal intracellular inclusion body formation. Whether proteasomes are
      irreversibly recruited into inclusion bodies in these protein misfolding
      disorders is a controversial subject. In addition, it has been proposed that the
      proteasomes may become clogged by the aggregated protein fragments, leading to
      impairment of the ubiquitin-proteasome system. Here, we show by fluorescence
      pulse-chase experiments in living cells that proteasomes are dynamically and
      reversibly recruited into inclusion bodies. As these recruited proteasomes remain
      catalytically active and accessible to substrates, our results challenge the
      concept of proteasome sequestration and impairment in Huntington's disease, and
      support the reported absence of proteasome impairment in mouse models of
      Huntington's disease. 

PMID- 24291263
TI  - Using routine diagnostic data as a method of surveillance of arboviral infection
      in travellers: a comparative analysis with a focus on dengue.
AB  - BACKGROUND: In a large part of the developing world, limited infectious disease
      surveillance is performed. In laboratory information management systems data on
      diagnostic requests is available and may be amenable to trend analyses. We
      explored this potential, using DENV diagnostic requests as a model. METHOD: Test
      results and anonymised information provided by clinicians were received for 8942
      patients from diagnostic centres in the Netherlands from January 2000 to May
      2011. The data were evaluated for completeness of a predefined minimal dataset
      and trends in DENV positive results by travel destination. Population travel data
      were obtained from a commercial registry, and dengue case notification data by
      country from WHO DengueNet. RESULTS: Vaccination history was rarely reported
      (0.4%); travel destination was completed for 42% of requests; trends in
      diagnostic requests and IgM positive tests for this subset correlated to the WHO
      DENV notifications for the three main travel destinations, with some
      discrepancies. Additionally, this approach may provide information on disease
      outbreaks with other pathogens causing diseases clinically similar to DENV. PCR
      data proved to be insufficient for trend monitoring by country. CONCLUSION: This
      approach is not straightforward, but shows potential for use as a source of
      additional information for surveillance of disease.

PMID- 24291264
TI  - Surprising causes of C5-carnitine false positive results in newborn screening.
AB  - During an 18-month period, we noticed an alarming increase of newborn screening
      false positivity rate in identifying isovaleric acidemia. In 50 of 50 newborns
      presenting elevated C5-carnitine, we confirmed the presence of pivaloylcarnitine.
      Exogenous pivalate administration had been previously identified as the causal
      agent of this concern. No pivalic-ester prodrug is commercially available in
      Belgium, but pivalic derivates are also used in the cosmetic industry as
      emollient under the term "neopentanoate". We have identified neopentanoate-esters
      in a nipple-fissure unguent that was provided to young mothers. Ceasing
      distribution of this product hugely reduced the C5-carnitine false positivity
      rate. 

PMID- 24291265
TI  - Functional dissociations in temporal preparation: evidence from dual-task
      performance.
AB  - Implicit preparation over time is a complex cognitive capacity important to
      optimize behavioral responses to a target occurring after a temporal interval,
      the so-called foreperiod (FP). If the FP occurs randomly and with the same a
      priori probability, shorter response times are usually observed with longer FPs
      than with shorter ones (FP effect). Moreover, responses are slower when the
      preceding FP was longer than the current one (sequential effects). It is still a
      matter of debate how different processes influence these temporal preparation
      phenomena. The present study used a dual-task procedure to understand how
      different processes, along the automatic-controlled continuum, may contribute to
      these temporal preparation phenomena. Dual-task demands were manipulated in two
      experiments using a subtraction task during the FP. This secondary task was
      administered in blocks (Experiment 1) or was embedded together with a baseline
      single-task in the same experimental session (Experiment 2). The results
      consistently showed that the size of the FP effect, but not that of sequential
      effects, is sensitive to dual-task manipulations. This functional dissociation
      unveils the multi-faceted nature of implicit temporal preparation: while the FP
      effect is due to a controlled, resource-consuming preparatory mechanism, a more
      automatic mechanism underlies sequential effects. 

PMID- 24291266
TI  - Anti-equality: social comparison in young children.
AB  - Young children dislike getting less than others, which might suggest a general
      preference for equal outcomes. However, young children are typically not averse
      to others receiving less than themselves. These results are consistent with two
      alternatives: young children might not have any preferences about others
      receiving less than themselves, or they might have preferences for others
      receiving less than themselves. We test these alternatives with 5- to 10-year-old
      children. We replicate previous findings that children will take a cost to avoid
      being at a relative disadvantage, but also find that 5- and 6-year-olds will
      spitefully take a cost to ensure that another's welfare falls below their own.
      This result suggests that the development of fairness includes overcoming an
      initial social comparison preference for others to get less relative to oneself. 

PMID- 24291267
TI  - IGZO thin film transistor biosensors functionalized with ZnO nanorods and
      antibodies.
AB  - We demonstrate a biosensor structure consisting of an IGZO (Indium-Gallium-Zinc
      Oxide) TFT (thin film transistor) and an extended sensing pad. The TFT acts as
      the sensing and readout device, while the sensing pad ensures the isolation of
      biological solution from the transistor channel layer, and meanwhile increases
      the sensing area. The biosensor is functionalized by first applying ZnO nanorods
      to increase the surface area for attracting electrical charges of EGFR (epidermal
      growth factor receptor) antibodies. The device is able to selectively detect 36.2
      fM of EGFR in the total protein solution of 0.1 ng/ml extracted from squamous
      cell carcinoma (SCC). Furthermore, the conjugation duration of the functionalized
      device with EGFR can be limited to 3 min, implying that the biosensor has the
      advantage for real-time detection.

PMID- 24291268
TI  - Fluorescent sensor for selective determination of copper ion based on N-acetyl-L
      cysteine capped CdHgSe quantum dots.
AB  - Using N-acetyl-L-cysteine as a stabilizer, well water-dispersed, high-quality and
      stable CdHgSe quantum dots were facilely synthesized via a simple aqueous phase
      method. The as-prepared N-acetyl-L-cysteine capped CdHgSe quantum dots were
      thoroughly characterized by transmission electron microscopy, X-ray diffraction
      spectroscopy and FTIR. A fluorescent sensor for selective determination of copper
      ions was developed using N-acetyl-L-cysteine capped CdHgSe quantum dots as
      fluorescent probe. The fluorescence intensity of N-acetyl-L-cysteine capped
      CdHgSe quantum dots decreased when interacted with copper ions due to the
      formation of coordination complex and aggregates. The method possesses high
      selectivity and is not influenced by some potential interferences such as Ag(+),
      Zn(2+), Co(2+) and Ni(2+). Under the optimal conditions, the change of
      fluorescence intensity (DeltaI) was linearly proportional to the concentration of
      copper ions in the range of 1.0*10(-9)-4.0*10(-7) mol L(-1), with a detection
      limit as low as 2.0*10(-10) mol L(-1) (S/N=3). The developed method had been
      successfully employed to determine Cu(2+) in shrimp and South-lake water samples,
      and the results were verified by atomic absorption spectroscopy. The fluorescent
      sensor was demonstrated to be selective, sensitive and simple for copper ion
      determination, and promise for practical applications.

PMID- 24291269
TI  - Who comes off best with closed chest? Aortic valve replacement in patients with
      high surgical risk.

PMID- 24291271
TI  - MicroRNAs and endothelial function: many challenges and early hopes for clinical
      applications.

PMID- 24291270
TI  - Pre-clinical diastolic dysfunction.
AB  - Pre-clinical diastolic dysfunction (PDD) has been broadly defined as left
      ventricular diastolic dysfunction without the diagnosis of congestive heart
      failure (HF) and with normal systolic function. PDD is an entity that remains
      poorly understood, yet has definite clinical significance. Although few original
      studies have focused on PDD, it has been shown that PDD is prevalent, and that
      there is a clear progression from PDD to symptomatic HF including dyspnea, edema,
      and fatigue. In diabetic patients and in patients with coronary artery disease or
      hypertension, it has been shown that patients with PDD have a significantly
      higher risk of progression to heart failure and death compared with patients
      without PDD. Because of these findings and the increasing prevalence of the heart
      failure epidemic, it is clear that an understanding of PDD is essential to
      decreasing patients' morbidity and mortality. This review will focus on what is
      known concerning pre-clinical diastolic dysfunction, including definitions,
      staging, epidemiology, pathophysiology, and the natural history of the disease.
      In addition, given the paucity of trials focused on PDD treatment, studies
      targeting risk factors associated with the development of PDD and therapeutic
      trials for heart failure with preserved ejection fraction will be reviewed. 

PMID- 24291272
TI  - Transcatheter versus surgical aortic valve replacement in patients with diabetes
      and severe aortic stenosis at high risk for surgery: an analysis of the PARTNER
      Trial (Placement of Aortic Transcatheter Valve).
AB  - OBJECTIVES: The goal of this study was to determine whether a less-invasive
      approach to aortic valve replacement (AVR) improves clinical outcomes in diabetic
      patients with aortic stenosis (AS). BACKGROUND: Diabetes is associated with
      increased morbidity and mortality after surgical AVR for AS. METHODS: Among
      treated patients with severe symptomatic AS at high risk for surgery in the
      PARTNER (Placement of Aortic Transcatheter Valve) trial, we examined outcomes
      stratified according to diabetes status of patients randomly assigned to receive
      transcatheter or surgical AVR. The primary outcome was all-cause mortality at 1
      year. RESULTS: Among 657 patients enrolled in PARTNER who underwent treatment,
      there were 275 patients with diabetes (145 transcatheter, 130 surgical). There
      was a significant interaction between diabetes and treatment group for 1-year all
      cause mortality (p = 0.048). Among diabetic patients, all-cause mortality at 1
      year was 18.0% in the transcatheter group and 27.4% in the surgical group (hazard
      ratio: 0.60 [95% confidence interval: 0.36 to 0.99]; p = 0.04). Results were
      consistent among patients treated via transfemoral or transapical routes. In
      contrast, among nondiabetic patients, there was no significant difference in all
      cause mortality at 1 year (p = 0.48). Among diabetic patients, the 1-year rates
      of stroke were similar between treatment groups (3.5% transcatheter vs. 3.5%
      surgery; p = 0.88), but the rate of renal failure requiring dialysis >30 days was
      lower in the transcatheter group (0% vs. 6.1%; p = 0.003). CONCLUSIONS: Among
      patients with diabetes and severe symptomatic AS at high risk for surgery, this
      post-hoc stratified analysis of the PARTNER trial suggests there is a survival
      benefit, no increase in stroke, and less renal failure from treatment with
      transcatheter AVR compared with surgical AVR. (The PARTNER Trial: Placement of
      AoRTic TraNscathetER Valve Trial; NCT00530894).

PMID- 24291273
TI  - Ticagrelor increases adenosine plasma concentration in patients with an acute
      coronary syndrome.
AB  - OBJECTIVES: This study aimed to investigate the impact of ticagrelor on adenosine
      plasma concentration (APC) in acute coronary syndrome (ACS) patients. BACKGROUND:
      Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The
      clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests
      that the drug has non-platelet-directed properties. Animal and in vitro models
      suggested that the "pleiotropic" properties of ticagrelor may be related to an
      interaction with adenosine metabolism. METHODS: We prospectively randomized 60
      ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid
      chromatography. To assess the mechanism of APC variation, we measured adenosine
      deaminase concentration, adenosine uptake by red blood cells, and cyclic
      adenosine monophosphate production by cells overexpressing adenosine receptors.
      The P2Y12-adenosine diphosphate receptor blockade was assessed by the vasodilator
      stimulated phosphoprotein index. RESULTS: Patients receiving ticagrelor had
      significantly higher APC than patients receiving clopidogrel (1.5 MUM
      [interquartile range: 0.98 to 1.7 MUM] vs. 0.68 MUM [interquartile range: 0.49 to
      0.78 MUM]; p < 0.01). The APC was not correlated with vasodilator-stimulated
      phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake
      by red blood cells compared with clopidogrel or controls (p < 0.01 for both
      comparisons). Adenosine deaminase activity was similar in serum of patients
      receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no
      direct impact on adenosine receptors (p = not significant). CONCLUSIONS:
      Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting
      adenosine uptake by red blood cells.

PMID- 24291275
TI  - Coronary flow reserve with a turbo: a warning for the use of adenosine as a
      provocative test in patients receiving ticagrelor?

PMID- 24291274
TI  - Let-7g improves multiple endothelial functions through targeting transforming
      growth factor-beta and SIRT-1 signaling.
AB  - OBJECTIVES: The present study aimed to explore the role of microribonucleic acid
      (miRNA) Let-7g in regulating endothelial functions. BACKGROUND: Derangement of
      miRNAs is implicated in the pathogenesis of cardiovascular diseases. Because the
      transforming growth factor (TGF)-beta pathway plays a regulatory role in
      endothelial functions, miRNAs targeted at TGF-beta signal cascade might affect
      vascular health. METHODS: Bioinformatics software predicted that Let-7g can
      influence the TGF-beta pathway by targeting 3 genes. The Let-7g's effects on
      multiple endothelial functions were first tested in endothelial cells (ECs) and
      then in apolipoprotein E knockout mice. Blood samples from lacunar stroke
      patients were also examined to further support Let-7g's effects on human
      subjects. RESULTS: Let-7g was experimentally confirmed to knock down the THBS1,
      TGFBR1, and SMAD2 genes in the TGF-beta pathway. PAI-I, one of the downstream
      effectors of the TGF-beta pathway, was also down-regulated by Let-7g. Let-7g
      decreased EC inflammation and monocyte adhesion and increased angiogenesis via
      the TGF-beta pathway. Furthermore, Let-7g reduced EC senescence through
      increasing SIRT-1 protein. Venous injection of Let-7g inhibitor into
      apolipoprotein E knockout mice caused overgrowth of vascular intima-media,
      overexpression of PAI-1, increased macrophage infiltration, and up-regulation of
      TGF-beta downstream genes in the carotid arteries. Let-7g's beneficial effects on
      EC were reduced, whereas the TGF-beta pathway was suppressed by ribonucleic acid
      interference. Restoration of the TGF-beta pathway also attenuated the effects of
      Let-7g overexpression. Low serum levels of Let-7g were associated with increased
      circulating PAI-1 levels. CONCLUSIONS: Decreased Let-7g levels impair endothelial
      function and increase the risks of cardiovascular diseases through targeting TGF
      beta and SIRT-1 signaling.

PMID- 24291276
TI  - Left atrial size and function: role in prognosis.
AB  - The author examines the ability of left atrial size and function to predict
      cardiovascular outcomes. Data are sufficient to recommend evaluation of left
      atrial volume in certain populations, and although analysis of atrial reservoir,
      conduit, and booster pump function trails in that regard, the gap is rapidly
      closing. In this state-of-the-art paper, the author reviews the methods used to
      assess left atrial size and function and discusses their role in predicting
      cardiovascular events in general and referral populations and in patients with
      atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart
      disease. 

PMID- 24291277
TI  - Veno-venous bridge in a neonate with hypoplastic left heart syndrome.

PMID- 24291278
TI  - Cardiac biomarkers, cardiotoxicity, and active collaboration: is this the final
      frontier or the wave we should catch?

PMID- 24291280
TI  - Patent foramen ovale closure challenged by left atrial chord.

PMID- 24291279
TI  - Frailty assessment in the cardiovascular care of older adults.
AB  - Due to the aging and increasingly complex nature of our patients, frailty has
      become a high-priority theme in cardiovascular medicine. Despite the recognition
      of frailty as a pivotal element in the evaluation of older adults with
      cardiovascular disease (CVD), there has yet to be a road map to facilitate its
      adoption in routine clinical practice. Thus, we sought to synthesize the existing
      body of evidence and offer a perspective on how to integrate frailty into
      clinical practice. Frailty is a biological syndrome that reflects a state of
      decreased physiological reserve and vulnerability to stressors. Upward of 20
      frailty assessment tools have been developed, with most tools revolving around
      the core phenotypic domains of frailty-slow walking speed, weakness, inactivity,
      exhaustion, and shrinking-as measured by physical performance tests and
      questionnaires. The prevalence of frailty ranges from 10% to 60%, depending on
      the CVD burden, as well as the tool and cutoff chosen to define frailty.
      Epidemiological studies have consistently demonstrated that frailty carries a
      relative risk of >2 for mortality and morbidity across a spectrum of stable CVD,
      acute coronary syndromes, heart failure, and surgical and transcatheter
      interventions. Frailty contributes valuable prognostic insights incremental to
      existing risk models and assists clinicians in defining optimal care pathways for
      their patients. Interventions designed to improve outcomes in frail elders with
      CVD such as multidisciplinary cardiac rehabilitation are being actively tested.
      Ultimately, frailty should not be viewed as a reason to withhold care but rather
      as a means of delivering it in a more patient-centered fashion. 

PMID- 24291281
TI  - Early increases in multiple biomarkers predict subsequent cardiotoxicity in
      patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab.
AB  - OBJECTIVES: The aim of this study was to determine if individual or multiple
      biomarkers are associated with cardiotoxicity in patients with breast cancer
      undergoing cancer therapy. BACKGROUND: Current methods to identify patients at
      risk for cardiotoxicity from cancer therapy are inadequate. METHODS: We measured
      8 biomarkers in a multicenter cohort of 78 patients with breast cancer undergoing
      doxorubicin and trastuzumab therapy: ultrasensitive troponin I (TnI), high
      sensitivity C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide
      (NT-proBNP), growth differentiation factor (GDF)-15, myeloperoxidase (MPO),
      placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt)
      1, and galectin (gal)-3. Cardiotoxicity, defined by the Cardiac Review and
      Evaluation Committee criteria, was assessed every 3 months for up to 15 months.
      Hazard ratios (HRs) of cardiotoxicity risk were assessed for each biomarker at
      baseline, at visit 2 (3 months), and as a function of the difference between
      visit 2 and baseline. Joint models were assessed for the most promising
      biomarkers. RESULTS: TnI, CRP, GDF-15, MPO, PlGF, and sFlt-1 levels increased
      from baseline to visit 2 (p < 0.05). A greater risk of cardiotoxicity was
      associated with interval changes in TnI (HR: 1.38 per SD; 95% confidence
      interval: 1.05 to 1.81; p = 0.02) and MPO (HR: 1.34 per SD; 95% confidence
      interval: 1.00 to 1.80; p = 0.048) and in models combining both markers (p =
      0.007 and p = 0.03, respectively). The risk of cardiotoxicity was 46.5% in
      patients with the largest changes in both markers (DeltaTnI >121.8 MUg/l;
      DeltaMPO >422.6 pmol/l). CONCLUSIONS: Early increases in TnI and MPO levels offer
      additive information about the risk of cardiotoxicity in patients undergoing
      doxorubicin and trastuzumab therapy. Independent validation of these findings is
      necessary before application to clinical practice.

PMID- 24291284
TI  - Expression pattern and function of alternative splice variants of glutamate-gated
      chloride channel in the housefly Musca domestica.
AB  - Glutamate-gated chloride channels (GluCls) mediate fast inhibitory
      neurotransmission in invertebrate nervous systems. cDNAs encoding two alternative
      splice variants (MdGluClB and C) of the GluCl subunit were cloned from the
      housefly Musca domestica. The expression patterns of three variants, including
      the previously reported MdGluClA, differed among the body parts (head, thorax,
      abdomen, and leg) of the adult housefly and among developmental stages (embryo,
      larva, pupa, and adult). The MdGluClA and B transcripts were abundant in the
      central nervous system of the adult, whereas the MdGluClC transcript was
      expressed in the central nervous system and as the predominant variant in the
      peripheral tissues. The sensitivities to the agonist glutamate and the allosteric
      activator ivermectin B1a did not differ between channels containing MdGluCl
      variants when they were singly or co-expressed in Xenopus oocytes. By contrast,
      MdGluClA and B channels were more sensitive to the channel blockers fipronil and
      picrotoxinin than was MdGluClC channels. Heteromeric channels containing
      different subunit variants were more sensitive to picrotoxinin than were
      homomeric channels. Heteromeric channels were more sensitive to fipronil than
      were homomeric MdGluClC channels but not than homomeric MdGluClA and B channels.
      These results suggest that functionally indistinguishable but pharmacologically
      distinct GluCls are expressed in a spatially and temporally distinct manner in
      the housefly. 

PMID- 24291283
TI  - Bleeding complications after surgical aortic valve replacement compared with
      transcatheter aortic valve replacement: insights from the PARTNER I Trial
      (Placement of Aortic Transcatheter Valve).
AB  - OBJECTIVES: This study sought to identify the incidence, predictors, and
      prognostic impact of bleeding complications (BC) after surgical aortic valve
      replacement (SAVR) compared with transcatheter aortic valve replacement (TAVR).
      BACKGROUND: Bleeding complications after SAVR and TAVR are frequent and may be
      associated with an unfavorable prognosis. METHODS: In the randomized controlled
      PARTNER (Placement of Aortic Transcatheter Valve) I trial, 657 patients from
      cohort A (operable high risk) were randomly assigned to SAVR or TAVR
      (transfemoral [TF] if iliofemoral access was suitable or transapical [TA] if not)
      and received the designated treatment. First-generation Edwards SAPIEN valves and
      delivery systems (Edwards Lifesciences, Irvine, California) were used for TAVR,
      through a 22- or 24-F sheath. The 30-day rates of major BC (modified Valve
      Academic Research Consortium definitions), predictors of BC, and their
      association with 1-year mortality were assessed. RESULTS: A total of 71 (22.7%),
      27 (11.3%), and 9 (8.8%) patients had major BC within 30 days of the procedure
      after SAVR, TF-TAVR, and TA-TAVR, respectively (p < 0.0001). SAVR was associated
      with a significantly higher 30-day rate of transfusion (17.9%) than either TF
      TAVR (7.1%) or TA-TAVR (4.8%; p < 0.0001). Independent predictors of major BC
      were the occurrence of major vascular complications and use of intraprocedural
      hemodynamic support among TF-TAVR patients, severe procedural complications
      requiring conversion to open surgery among TA-TAVR patients, and the presence of
      low hemoglobin at baseline among SAVR patients. Major BC was identified as the
      strongest independent predictor of 1-year mortality among the full cohort.
      However, risk-adjusted analyses demonstrated a significant interaction between BC
      and treatment strategy with respect to mortality, suggesting that BC after SAVR
      have a greater impact on prognosis than after TAVR. CONCLUSIONS: Among high-risk
      aortic stenosis patients enrolled in the PARTNER I randomized trial, BC were more
      common after SAVR than after TAVR and were also associated with a worse long-term
      prognosis. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial;
      NCT00530894).

PMID- 24291285
TI  - The ABC gene family in arthropods: comparative genomics and role in insecticide
      transport and resistance.
AB  - About a 100 years ago, the Drosophila white mutant marked the birth of Drosophila
      genetics. The white gene turned out to encode the first well studied ABC
      transporter in arthropods. The ABC gene family is now recognized as one of the
      largest transporter families in all kingdoms of life. The majority of ABC
      proteins function as primary-active transporters that bind and hydrolyze ATP
      while transporting a large diversity of substrates across lipid membranes.
      Although extremely well studied in vertebrates for their role in drug resistance,
      less is known about the role of this family in the transport of endogenous and
      exogenous substances in arthropods. The ABC families of five insect species, a
      crustacean and a chelicerate have been annotated in some detail. We conducted a
      thorough phylogenetic analysis of the seven arthropod and human ABC protein
      subfamilies, to infer orthologous relationships that might suggest conserved
      function. Most orthologous relationships were found in the ABCB half transporter,
      ABCD, ABCE and ABCF subfamilies, but specific expansions within species and
      lineages are frequently observed and discussed. We next surveyed the role of ABC
      transporters in the transport of xenobiotics/plant allelochemicals and their
      involvement in insecticide resistance. The involvement of ABC transporters in
      xenobiotic resistance in arthropods is historically not well documented, but an
      increasing number of studies using unbiased differential gene expression analysis
      now points to their importance. We give an overview of methods that can be used
      to link ABC transporters to resistance. ABC proteins have also recently been
      implicated in the mode of action and resistance to Bt toxins in Lepidoptera.
      Given the enormous interest in Bt toxicology in transgenic crops, such findings
      will provide an impetus to further reveal the role of ABC transporters in
      arthropods. 

PMID- 24291286
TI  - Chromatin-induced spindle assembly plays an important role in metaphase
      congression of silkworm holocentric chromosomes.
AB  - The kinetochore plays important roles in cell cycle progression. Interactions
      between chromosomes and spindle microtubules allow chromosomes to congress to the
      middle of the cell and to segregate the sister chromatids into daughter cells in
      mitosis. The chromosome passenger complex (CPC), composed of the Aurora B kinase
      and its regulatory subunits INCENP, Survivin, and Borealin, plays multiple roles
      in these chromosomal events. In the genome of the silkworm, Bombyx mori, which
      has holocentric chromosomes, the CPC components and their molecular interactions
      were highly conserved. In contrast to monocentric species, however, the silkworm
      CPC co-localized with the chromatin-driven spindles on the upper side of
      prometaphase chromosomes without forming bipolar mitotic spindles. Depletion of
      the CPC by RNAi arrested the cell cycle progression at prometaphase and disrupted
      the microtubule network of the chromatin-driven spindles. Interestingly,
      depletion of mitotic centromere-associated kinesin (MCAK) recovered formation of
      the microtubule network but did not overcome the cell cycle arrest at
      prometaphase. These results suggest that the CPC modulates the chromatin-induced
      spindle assembly and metaphase congression of silkworm holocentric chromosomes. 

PMID- 24291282
TI  - Coxsackie and adenovirus receptor is a modifier of cardiac conduction and
      arrhythmia vulnerability in the setting of myocardial ischemia.
AB  - OBJECTIVES: The aim of this study was to investigate the modulatory effect of the
      coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia
      vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable
      component in the risk of ventricular fibrillation during myocardial infarction
      has been well established. A recent genome-wide association study of ventricular
      fibrillation during acute myocardial infarction led to the identification of a
      locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR
      encodes the CAR, a cell adhesion molecule predominantly located at the
      intercalated disks of the cardiomyocyte. METHODS: The correlation between CAR
      transcript levels and rs2824292 genotype was investigated in human left
      ventricular samples. Electrophysiological studies and molecular analyses were
      performed using CAR haploinsufficient (CAR+/-) mice. RESULTS: In human left
      ventricular samples, the risk allele at the chr21q21 genome-wide association
      study locus was associated with lower CXADR messenger ribonucleic acid levels,
      suggesting that decreased cardiac levels of CAR predispose to ischemia-induced
      ventricular fibrillation. Hearts from CAR+/- mice displayed slowing of
      ventricular conduction in addition to an earlier onset of ventricular arrhythmias
      during the early phase of acute myocardial ischemia after ligation of the left
      anterior descending artery. Expression and distribution of connexin 43 were
      unaffected, but CAR+/- hearts displayed increased arrhythmia susceptibility on
      pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR+/-
      myocytes showed reduced sodium current magnitude specifically at the intercalated
      disk. Moreover, CAR coprecipitated with NaV1.5 in vitro, suggesting that CAR
      affects sodium channel function through a physical interaction with NaV1.5.
      CONCLUSIONS: CAR is a novel modifier of ventricular conduction and arrhythmia
      vulnerability in the setting of myocardial ischemia. Genetic determinants of
      arrhythmia susceptibility (such as CAR) may constitute future targets for risk
      stratification of potentially lethal ventricular arrhythmias in patients with
      coronary artery disease.

PMID- 24291287
TI  - Dielectric spectroscopy study of myoglobin in glycerol-water mixtures.
AB  - Due to the interest in protein dynamics, there are numerous dielectric relaxation
      studies of proteins in water and in glass-forming aqueous solvents such as
      glycerol-water mixtures. In the regime of low frequencies, the inevitable dc
      conductivity of such systems limits the resolution of dynamics that are slow
      compared with the solvent relaxation. Solutions of myoglobin in glycerol/water
      mixtures of various compositions are measured by dielectric spectroscopy in the
      frequency range from 10mHz to 10MHz. The resolution of low frequency modes is
      improved by two approaches: electrical 'cleaning' and the analysis of the
      derivative of the real component of permittivity, which shows no direct signature
      of dc-conductivity. Effects of internal interfacial polarization are also
      addressed by measuring the same solvents in confinement as well as mixed with
      glass beads. We find two processes, the structural relaxation of the solvent and
      the slower rotational mode of the protein, with no indication at even lower
      frequencies of a dielectric signature of fluctuations associated with protein
      dynamics. 

PMID- 24291289
TI  - First case of peritoneal cystic echinococcosis in a domestic cat caused by
      Echinococcus granulosus sensu stricto (genotype 1) associated to feline
      immunodeficiency virus infection.
AB  - A new cystic echinococcosis case in a cat in Uruguay is reported herein. The cat
      was taken to a veterinary clinic in Rocha city, Uruguay, due to dyspnea,
      constipation and abdominal enlargement. During surgery a large quantity of cysts
      was retrieved from the abdominal cavity. The cysts were morphologically studied
      and confirmed as Echinococcus granulosus sensu stricto (genotype 1) by molecular
      tools using cytochrome oxidase submit 1 and small subunit ribosomal RNA gene as
      target genes. Moreover, for the first time a coinfection with feline
      immunodeficiency virus (FIV) was detected. FIV-induced immunosuppression could be
      a determining factor in the development of cystic echinococcosis in cats. 

PMID- 24291288
TI  - Peripheral immunophenotype and viral promoter variants during the asymptomatic
      phase of feline immunodeficiency virus infection.
AB  - Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic
      phase during chronic infection. Despite the lack of overt clinical disease, the
      asymptomatic phase is characterized by persistent immunologic impairment. In the
      peripheral blood obtained from cats experimentally infected with FIV-C for
      approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio.
      We cloned and sequenced the FIV-C long terminal repeat containing the viral
      promoter from cells infected with the inoculating virus and from in vivo-derived
      peripheral blood mononuclear cells and CD4 T cells isolated at multiple time
      points throughout the asymptomatic phase. Relative to the inoculating virus,
      viral sequences amplified from cells isolated from all of the infected animals
      demonstrated multiple single nucleotide mutations and a short deletion within the
      viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in
      the U3 promoter AP-1 site was identified at multiple time points from all of the
      infected animals but not within cell-associated viral RNA. In contrast, no
      mutations were identified within the sequence of the viral dUTPase gene amplified
      from PBMC isolated at approximately 5 years post-infection relative to the
      inoculating sequence. The possible implications of these mutations to viral
      pathogenesis are discussed. 

PMID- 24291290
TI  - Phylogeny, ultrastructure and histopathology of Myxobolus lomi sp. nov., a
      parasite of Prochilodus lineatus (Valenciennes, 1836) (Characiformes:
      Prochilodontidae) from the Peixes River, Sao Paulo State, Brazil.
AB  - This paper presents the morphological, histological, molecular and
      ultrastructural data on Myxobolus lomi sp. nov., a parasite of the gill filaments
      of Prochilodus lineatus from the Peixes River (48o06'38"W; 22o 49'53.1"S), Sao
      Paulo State, Brazil. From 20 P. lineatus specimens examined, 90.0% (n=18) were
      infected. The plasmodia were white and round, measuring 250 to 300MUm in diameter
      and the development occurred in the base of the gill filament. The spores showed
      symmetrical and smooth valves, with the polar filament having 8 to 11 coils. A
      thorough comparison with all the Myxobolus species described so far is provided.
      A partial sequencing of the 18S rDNA gene revealed approximately 1600-bp. The
      Myxobolus species parasite of P. lineatus did not match any of the Myxozoa
      available in GenBank. In the phylogenetic analysis, M. lomi sp. nov. is clustered
      with ten other species and only four of these parasites were from gills.
      Histological analysis of P. lineatus gills infected by M. lomi sp. nov. revealed
      numerous well-delimited cysts at the base of the primary lamella, between
      connective tissue and bone, next to the gill arteries. However no pronounced
      inflammatory response was found at the infection site. 

PMID- 24291292
TI  - Concurrent extraction and reaction for the production of biodiesel from wet
      microalgae.
AB  - This work addresses a reliable in situ transesterification process which
      integrates lipid extraction from wet microalgae, and its conversion to biodiesel,
      with a yield higher than 90 wt.%. This process enables single-step production of
      biodiesel from microalgae by mixing wet microalgal cells with solvent, methanol,
      and acid catalyst; and then heating them in one pot. The effects of reaction
      parameters such as reaction temperature, wet cell weight, reaction time, and
      catalyst volume on the conversion yield are investigated. This simultaneous
      extraction and transesterification of wet microalgae may enable a significant
      reduction in energy consumption by eliminating the drying process of algal cells
      and realize the economic production of biodiesel using wet microalgae.

PMID- 24291293
TI  - Psychometric assessment of the MSAS-SF and the FACIT-Fatigue Scale in Spanish
      speaking patients with cancer in Uruguay.
AB  - CONTEXT: Several instruments have been developed to assess the symptom burden and
      fatigue produced by cancer and its treatment. However, little research has been
      conducted in Latin American Spanish-speaking patients. OBJECTIVES: The aim of the
      study was to assess the psychometric properties of the Spanish versions of two
      commonly used patient-reported outcome measures, the Memorial Symptom Assessment
      Scale-Short Form (MSAS-SF), and the fatigue subscale of the Functional Assessment
      of Cancer Therapy-General (FACT-G), the FACIT-Fatigue. METHODS: A classic
      psychometric approach was followed to assess the reliability and validity of the
      instruments. Responsiveness to change and effect sizes were calculated. RESULTS:
      The translated version of the MSAS-SF proved to be comprehensible and easy to
      complete. Cronbach alpha reliability coefficients ranged from acceptable to
      excellent for the MSAS-SF subscale scores and the FACIT-Fatigue. There was
      evidence of convergent validity between the physical and the psychological
      subscales of the instruments. The MSAS-SF could discriminate among the known
      groups according to Eastern Cooperative Oncology performance status and level of
      anemia, and showed responsiveness to change of symptom burden at two times of
      treatment. CONCLUSION: The study showed that both the MSAS-SF and the FACIT
      Fatigue have good reliability and validity for use with patients with cancer in
      Uruguay. When used simultaneously, these instruments may provide a complete
      picture of the impact of cancer and its treatment on the patient's quality of
      life.

PMID- 24291291
TI  - Adolescents and alcohol: acute sensitivities, enhanced intake, and later
      consequences.
AB  - Adolescence is an evolutionarily conserved developmental period characterized by
      notable maturational changes in the brain along with various age-related
      behavioral characteristics, including the propensity to initiate alcohol and
      other drug use and consume more alcohol per occasion than adults. After a brief
      review of adolescent neurobehavioral function from an evolutionary perspective,
      the paper will turn to assessment of adolescent alcohol sensitivity and
      consequences, with a focus on work from our laboratory. After summarizing
      evidence showing that adolescents differ considerably from adults in their
      sensitivity to various effects of alcohol, potential contributors to these age
      typical sensitivities will be discussed, and the degree to which these findings
      are generalizable to other drugs and to human adolescents will be considered.
      Recent studies are then reviewed to illustrate that repeated alcohol exposure
      during adolescence induces behavioral, cognitive, and neural alterations that are
      highly specific, replicable, persistent and dependent on the timing of the
      exposure. Research in this area is in its early stages, however, and more work
      will be necessary to characterize the extent of these neurobehavioral alterations
      and further determine the degree to which observed effects are specific to
      alcohol exposure during adolescence. 

PMID- 24291294
TI  - A pilot study of the experience of family caregivers of patients with advanced
      pancreatic cancer using a mixed methods approach.
AB  - CONTEXT: Pancreatic cancer presents a wide spectrum of significant
      symptomatology. The high symptom burden, coupled with a rapidly fatal diagnosis,
      limits preparation or time for adjustment for both patients and their family
      caregivers. From the initial diagnosis and throughout the illness experience, the
      physical and emotional demands of caregiving can predispose caregivers themselves
      to illness and a greater risk of mortality. Understanding the negative and
      positive aspects of caregiving for patients with advanced pancreatic cancer will
      inform interventions that promote positive caregiver outcomes and support
      caregivers in their role. OBJECTIVES: To provide feasibility data for a larger,
      mixed methods, longitudinal study focused on the experience of family caregivers
      of patients with advanced pancreatic cancer and preliminary qualitative data to
      substantiate the significance of studying this caregiver population. METHODS:
      This was a mixed methods study guided by the Stress Process Model. Eight family
      caregivers of patients with advanced pancreatic cancer from oncology practices of
      a university-affiliated medical center were surveyed. RESULTS: The pilot results
      supported the ability to recruit and retain participants and informed recruitment
      and data collection procedures. The qualitative results provided preliminary
      insights into caregiver experiences during the diagnosis and treatment phases.
      Key findings that substantiated the significance of studying these caregivers
      included the caregiving context of the history of sentinel symptoms, the crisis
      of diagnosis, the violation of assumptions about life and health, recognition of
      the circle of association, and contextual factors, as well as primary and
      secondary stressors, coping strategies, resources, discoveries, gains and growth,
      associated changes/transitions, and unmet caregiver needs. CONCLUSION: Findings
      indicated caregivers' willingness to participate in research, highlighted the
      negative and positive aspects of the caregiver experience, and reinforced the
      significance of the future study and the need to develop interventions to support
      family caregivers in their roles.

PMID- 24291295
TI  - Authors' reply to Phan and Hui.

PMID- 24291296
TI  - Efficacy and safety of a six-hour continuous overlap method for converting
      intravenous to transdermal fentanyl in cancer pain.
AB  - CONTEXT: Managing cancer pain often requires opioid medications, such as
      fentanyl, which is frequently initiated parenterally, and then converted to
      transdermal form. Little evidence exists to guide this conversion. OBJECTIVES: To
      observe the efficacy and safety of a six-hour continuous overlap method for
      converting intravenous fentanyl (IVF) to transdermal fentanyl (TF) in patients
      with cancer pain. METHODS: We switched from IVF to TF using a 1:1 (IVF:TF)
      conversion ratio and overlapped a continuous, nontapered dose of IVF until six
      hours after TF placement. Pain intensity by Numeric Rating Scale, number of
      rescue analgesic doses, and presence and severity of opioid-related adverse
      events were recorded immediately before TF placement, and at six, 12, 18, and 24
      hours thereafter. RESULTS: A total of 17 consecutive patients with cancer pain
      controlled on IVF were converted to TF. Median age was 65 years, 10 were female,
      and all had Stage IV cancer. Pain intensity at six and 24 hours remained stable;
      a slight but statistically significant increase in Numeric Rating Scale was noted
      at 12 and 18 hours (P=0.01 and 0.02, respectively); however, there was no
      significant increase in number of rescue doses throughout the observation period.
      Only one patient experienced opioid-related adverse events. CONCLUSION: A
      continuous six-hour overlap method is a safe and effective strategy when
      converting from IVF to TF in patients with cancer pain. A slight increase in pain
      intensity may occur, but does not lead to increased rescue doses.

PMID- 24291297
TI  - Takotsubo cardiomyopathy secondary in part to cancer-related pain crisis: a case
      report.

PMID- 24291298
TI  - Getting to proven: evaluating quality across all of palliative care.

PMID- 24291299
TI  - Important clinical findings for chemotherapy-induced nausea and vomiting:
      commentary on Molassiotis et al.

PMID- 24291300
TI  - Barriers to climate-friendly food choices among young adults in Finland.
AB  - The aim of the study was to examine how young adults in Finland perceive barriers
      to climate-friendly food choices and how these barriers are associated with their
      choices. The participants were 350 university students of the social and
      behavioral sciences who completed a questionnaire during class. The study found
      that the barriers the participants perceived as being the most relevant were
      different from those that were associated with the omission of climate-friendly
      food choices. High prices were perceived as the most relevant barrier, but were
      only weakly associated with the participants' food choices. Instead, habit and
      disbelief in the effects of food consumption on the climate were found to be the
      barriers that had the greatest association with climate-friendly choices.
      Moreover, women considered high prices and poor supply more important compared to
      men, whereas men considered disbelief and habit more important. In addition,
      vegetarians perceived fewer barriers than those who followed other diets. The
      findings increase our understanding of young adults' perceptions of barriers to
      climate-friendly food choices, as well as their effects. 

PMID- 24291301
TI  - Complex behaviour in a dengue model with a seasonally varying vector population.
AB  - In recent decades, dengue fever and dengue haemorrhagic fever have become a
      substantial public health concern in many subtropical and tropical countries
      throughout the world. Many of these regions have strong seasonal patterns in
      rainfall and temperature which are directly linked to the transmission of dengue
      through the mosquito vector population. Our study focuses on the development and
      analysis of a strongly seasonally forced, multi-subclass dengue model. This model
      is a compartment-based system of first-order ordinary differential equations with
      seasonal forcing in the vector population and also includes host population
      demographics. Our analysis of this model focuses particularly on the existence of
      deterministic chaos in regions of the parameter space which potentially hinders
      application of the model to predict and understand future outbreaks. The
      numerically efficient 0-1 test for deterministic chaos suggested by Gottwald and
      Melbourne (2004) [18] is used to analyze the long-term behaviour of the model as
      an alternative to Lyapunov exponents. Various solutions types were found to exist
      within the studied parameter range. Most notable are the existence of isola n
      cycle solutions before the onset of deterministic chaos. Analysis of the seasonal
      model with the 0-1 test revealed the existence of three disconnected regions in
      parameter space where deterministic chaos exists in the single subclass model.
      Knowledge of these regions and how they relate to the parameters of the model
      gives greater confidence in the predictive power of the seasonal model. 

PMID- 24291302
TI  - Estimation of kinetic parameters in an S-system equation model for a metabolic
      reaction system using the Newton-Raphson method.
AB  - Metabolic reaction systems can be modeled easily in terms of S-system type
      equations if their metabolic maps are available. This study therefore proposes a
      method for estimating parameters in decoupled S-system equations on the basis of
      the Newton-Raphson method and elucidates the performance of this estimation
      method. Parameter estimation from the time-course data of metabolite
      concentrations reveals that the parameters estimated are highly accurate,
      indicating that the estimation algorithm has been constructed correctly. The
      number of iterations is small and the calculation converges in a very short time
      (usually less than 1s). The method is also applied to time course data with noise
      and found to estimate parameters efficiently. Results indicate that the present
      method has the potential to be extended to a method for estimating parameters in
      large-scale metabolic reaction systems. 

PMID- 24291303
TI  - Developmental programming of the HPA and HPG axes by early-life stress in male
      and female song sparrows.
AB  - Variation in early environmental conditions can have long-term effects on
      physiology and behavior, a process referred to as developmental programming. In
      particular, exposure to early-life stressors can have long-term effects on
      regulation of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary
      gonadal (HPG) axes. Although these effects have been well documented in mammals,
      less is known about how early-life stress affects regulation of these endocrine
      systems in non-mammalian species. In the current study, we determined the long
      term effects of early-life food restriction or corticosterone (CORT) treatment on
      the HPA axis of song sparrows (Melospiza melodia), including the responses to
      restraint stress, dexamethasone challenge, and ACTH challenge. In addition, we
      assessed long-term effects on the HPG axis by measuring sex steroid levels
      (testosterone in males and 17beta-estradiol in females) before and after a
      gonadotropin-releasing hormone (GnRH) challenge. Subjects treated with CORT
      during development had larger increases in CORT in response to ACTH challenge
      than food-restricted or control subjects. Neither treatment affected the
      responses of CORT to restraint or dexamethasone. CORT-treated males also had
      higher initial testosterone levels, but neither treatment affected testosterone
      levels post-GnRH. Lastly, although GnRH challenge failed to increase circulating
      estradiol levels in females, females exposed to food restriction or CORT
      treatment had lower estradiol levels than control females. These results show
      that exposure to stress can developmentally program the endocrine system of
      songbirds and illustrate the importance of considering developmental conditions
      when determining the factors responsible for inter-individual variation in
      endocrine regulation. 

PMID- 24291304
TI  - Environmental estrogens inhibit growth of rainbow trout (Oncorhynchus mykiss) by
      modulating the growth hormone-insulin-like growth factor system.
AB  - Although environmental estrogens (EE) have been found to disrupt a wide variety
      of developmental and reproductive processes in vertebrates, there is a paucity of
      information concerning their effects on organismal growth, particularly
      postembryonic growth. In this study, we exposed juvenile rainbow trout
      (Oncorhynchus mykiss) to 17beta-estradiol (E2) beta-sitosterol (betaS), or 4-n
      nonylphenol (NP) to assess the effects of EE on overall organismal growth and on
      the growth hormone-insulin-like-growth factor (GH-IGF) system. EE treatment
      significantly reduced food conversion, body condition, and body growth. EE
      inhibited growth resulted from alterations in peripheral elements of the GH-IGF
      system, which includes multiple GH receptors (GHRs), IGFs, and IGF receptors
      (IGFRs). In general, E2, betaS, and NP reduced the expression of GHRs, IGFs, and
      IGFRs; however, the effects varied in an EE-, tissue-, element type-specific
      manner. For example, in liver, E2 was more efficacious than either betaS, and NP
      in reducing GHR expression, and the effect of E2 was greater on GHR 1 than GHR2
      mRNA. By contrast, in gill, all EEs affected GHR expression in a similar manner
      and there was no difference in the effect on GHR1 and GHR 2 mRNA. With regard to
      IGF expression, all EEs reduced hepatic IGF1 and IGF2 mRNA levels, whereas as in
      gill, only E2 and NP significantly reduced IGF1 and IGF2 expression. Lastly, E2
      and NP reduced the expression of IGFR1A and IGFR1B mRNA expression similarly in
      gill and red and white muscle, whereas betaS had no effect on expression of IGFR
      mRNAs. These findings indicate that EEs disrupt post-embryonic growth by reducing
      GH sensitivity, IGF production, and IGF sensitivity. 

PMID- 24291305
TI  - The forkhead transcription factor FOXO1 stimulates the expression of the
      adipocyte resistin gene.
AB  - Resistin is known as an adipocyte-specific hormone that can cause insulin
      resistance and decrease adipocyte differentiation. It can be regulated by
      transcriptional factors, but the possible role of forkhead transcription factor
      FOXO1 in regulating resistin gene expression is still unknown. Using 3T3
      fibroblast and C3H10T1/2 and 3T3-L1 adipocytes, we found that transient
      overexpression of a non-phosphorylatable, constitutively active FOXO1, but not
      the wild type of FOXO1 or a DNA binding-deficient FOXO1, activated resistin
      promoter-directed luciferase expression. However, transient overexpression of a
      dominant-negative FOXO1 inactivated resistin promoter activity and reduced
      resistin mRNA expression. These observations indicate that the action of FOXO1 on
      resistin gene expression requires the activation of FOXO1 and that the effect of
      FOXO1 depends on the phosphorylation and dephosphorylation of FOXO1. The FOXO1
      protein target sites on the resistin promoter were localized to the proximal 
      3545 to -787bp of 5'-flanking region of the resistin promoter. A chromatin
      immunoprecipitation assay also showed that FOXO1 bound the resistin promoter at
      nucleotide regions of -1539 to -1366bp and -1016 to -835bp, but not at the
      regions of -795 to -632bp. Results of this study suggest that FOXO1 transcription
      factor likely activates the expression of adipocyte resistin gene via direct
      association with the upstream resistin promoter. 

PMID- 24291306
TI  - Effect of ultrasound on the activity and conformation of alpha-amylase, papain
      and pepsin.
AB  - The effect of ultrasound on the activity of alpha-amylase, papain and pepsin was
      investigated and the mechanism of the effect was explored by determining their
      conformational changes. With the irradiation of power ultrasound, the activity of
      alpha-amylase and papain was inhibited, while the activity of pepsin was
      activated. According to the analysis of circular dichroism, Fourier transform
      infrared and fluorescence spectroscopy, the pio -> pi(*) amide transitions and
      secondary structural components, especially beta-sheet, of these three enzymes
      were significantly influenced by ultrasound. The tryptophan fluorescence
      intensity of the three enzymes was also observed to be affected by sonication.
      Furthermore, it was found that the pepsin molecule might gradually be resistant
      to prolonged ultrasonic treatment and recover from the ultrasound-induced damage
      to its original structure. The results suggested that the activity of alpha
      amylase, papain and pepsin could be modified by ultrasonic treatment mainly due
      to the variation of their secondary and tertiary structures.

PMID- 24291308
TI  - Incidentalology: A developing urological sub-specialty.
AB  - OBJECTIVE: To identify the incidence and features of significant incidental
      findings discussed at our departmental multidisciplinary team meeting (MDM). The
      improved quality of radiological imaging has resulted in increased rates of
      incidental findings. Although some may be trivial, many have clinical
      significance and early diagnosis and treatment may be beneficial. METHODS: A
      retrospective analysis was performed of all cases discussed at the MDM between
      January 2012 and February 2013. Cases were divided into two groups--Group 1
      consisted of patients whose initial imaging was performed for a urological
      presentation which resulted in a synchronous finding; Group 2 consisted of
      patients who were referred with a synchronous urological finding for discussion
      following investigation of an initial benign urological condition or a non
      urological condition. RESULTS: 696 patients were discussed at 53 MDMs. 109
      (15.7%) patients had incidental findings. 61 (56%) of these were in Group 1. 16
      (26.2%) were synchronous malignant diagnoses, 25 (41%) were benign and 20 (32.8%)
      were indeterminate. 48 (44%) patients in Group 2 - 40 (83.3%) were renal in
      origin and 30 (75%) of these proceeded to surgery. The median tumour size was 3.2
      cm (Range: 1.2 cm-10 cm). One patient had radio-frequency ablation. Two were
      referred for palliative care. Seven patients are under ongoing surveillance--the
      median size of these lesions is 3.6 cm (Range: 2.1 cm-8.3 cm). CONCLUSION: A
      substantial workload is generated from the investigation of incidental findings
      discussed at MDM--these now represent the majority of the caseload for renal
      cancer surgery.

PMID- 24291307
TI  - A new way to apply ultrasound in cross-flow ultrafiltration: application to
      colloidal suspensions.
AB  - A new coupling of ultrasound device with membrane process has been developed in
      order to enhance cross-flow ultrafiltration of colloidal suspensions usually
      involved in several industrial applications included bio and agro industries,
      water and sludge treatment. In order to reduce mass transfer resistances induced
      by fouling and concentration polarization, which both are main limitations in
      membrane separation process continuous ultrasound is applied with the help of a
      vibrating blade (20 kHz) located in the feed channel all over the membrane
      surface (8mm between membrane surface and the blade). Hydrodynamic aspects were
      also taking into account by the control of the rectangular geometry of the feed
      channel. Three colloidal suspensions with different kinds of colloidal
      interaction (attractive, repulsive) were chosen to evaluate the effect of their
      physico-chemical properties on the filtration. For a 90 W power (20.5 W cm(-2))
      and a continuous flow rate, permeation fluxes are increased for each studied
      colloidal suspension, without damaging the membrane. The results show that the
      flux increase depends on the initial structural properties of filtered dispersion
      in terms of colloidal interaction and spatial organizations. For instance, a
      Montmorillonite Wyoming-Na clay suspension was filtered at 1.5 * 10(5)Pa
      transmembrane pressure. Its permeation flux is increased by a factor 7.1, from
      13.6 L m(-2)h(-1) without ultrasound to 97 L m(-2)h(-1) with ultrasound.

PMID- 24291309
TI  - Performance evaluation of anaerobic hybrid reactors with different packing media
      for treating wastewater of mild alkali treated rice straw in ethanol fermentation
      process.
AB  - Four anaerobic hybrid reactors with different packing media viz. gravel (R1),
      pumice stone (R2), polypropylene saddles (R3) and ceramic saddles (R4) were
      operated in semi-continuous mode. Biomethanation potential of the wastewater
      generated during alkali-treatment of rice straw in ethanol production process was
      investigated at ambient conditions. The reactors were operated with varying
      organic loading rates (0.861-4.313 g COD l(-1) d(-1)) and hydraulic retention
      time (3-15 days). Higher COD removal efficiency (69.2%) and methane yield (0.153
      l CH4 g(-1) CODadded) were achieved in reactor R2 at 15 days HRT. Modified Stover
      Kincannon model was applied to estimate the bio-kinetic coefficients and fitness
      of the model was checked by the regression coefficient for all the reactors. The
      model showed an excellent correlation between the experimental and predicted
      values. The present study demonstrated the treatment of wastewater from alkali
      treated rice straw for production of biogas.

PMID- 24291310
TI  - Strong influence of medium pH condition on gas-phase biofilter ammonia removal,
      nitrous oxide generation and microbial communities.
AB  - Effects of pH on gas-phase biofilter performance including NH3 removal efficiency
      (RE), N2O generation, and microbial communities of ammonia oxidizers and
      denitrifies, are examined. A two-step experiment was carried out on four
      biofilters for 130 days. In step 1 with pH 8.0, NH3 REs were 85-95% and N2O
      concentrations were 0.1-0.4 ppm. In step 2, pH was adjusted to 4.5, 6.0, 8.0, and
      9.5 in four biofilters, respectively. The acidified biofilters showed higher NH3
      REs than the alkalized biofilters. N2O concentration in biofilters with pH 4.5
      and 6.0 was increased to 1.5 and 0.5 ppm, respectively, while no change in the
      alkalized biofilters. Comparing to communities in step 1, the amoA and nosZ
      structures were altered when pH was changed to 4.5 and 6.0, but not at 9.5.
      Abundance of amoA was reduced at pH 4.5, while nosZ abundance was increased with
      considerably less changes in acidified biofilters compared to alkalized
      biofilters.

PMID- 24291311
TI  - Pretreatment of e-waste and mutation of alkali-tolerant cyanogenic bacteria
      promote gold biorecovery.
AB  - Gold was recovered from electronic scrap material (ESM) as gold-cyanide complex
      by Chromobacterium violaceum which produces cyanide as a secondary metabolite.
      The effect of pretreatment and mutation of alkali-tolerant bacteria was examined.
      Pretreatment dissolved most of the base metals, thereby reducing competition for
      the cyanide ion from other metals. As the pKa of HCN is 9.3, alkaline pH
      increases the cyanide ion concentration available for bioleaching, and the
      bacteria were mutated to grow at pH 9, 9.5 and 10. Results showed that at 0.5%
      pulp density of pretreated ESM, mutated bacteria attained gold biorecovery of 18%
      at pH 9, 22.5% at pH 9.5 and 19% at pH 10 while that of unadapted bacteria (at pH
      7) yielded only 11% recovery. Results showed that gold bioleaching efficiency
      from electronic scrap was enhanced under alkaline conditions with mutated
      bacteria compared to bioleaching at physiological pH (around 7) of C. violaceum.

PMID- 24291312
TI  - Development of a sixth-generation down-flow hanging sponge (DHS) reactor using
      rigid sponge media for post-treatment of UASB treating municipal sewage.
AB  - A sixth-generation down-flow hanging sponge reactor (DHS-G6), using rigid sponge
      media, was developed as a novel aerobic post-treatment unit for upflow anaerobic
      sludge blanket (UASB) treating municipal sewage. The rigid sponge media were
      manufactured by copolymerizing polyurethane with epoxy resin. The UASB and DHS
      system had a hydraulic retention time (HRT) of 10.6 h (8.6 h for UASB and 2 h for
      DHS) when operated at 10-28  degrees C. The system gave reasonable organic and
      nitrogen removal efficiencies. The final effluent had a total biochemical oxygen
      demand of only 12 mg/L and a total Kjeldahl nitrogen content of 6 mg/L. The DHS
      reactor gave particularly good nitrification performance, which was attributed to
      the new rigid sponge media. The sponge media helped to provide a sufficient HRT,
      and retained a high biomass concentration, extending the solids retention time.
      The DHS reactor maintained a high dissolved oxygen concentration under natural
      ventilation.

PMID- 24291313
TI  - Volatile fatty acids (VFAs) accumulation and microbial community structure of
      excess sludge (ES) at different pHs.
AB  - This study aimed at exploring the potential of volatile fatty acids (VFAs)
      produced from excess sludge (ES) as a new cost-effective internal carbon source
      in wastewater treatment processes. The optimal condition for VFA accumulation and
      the bacterial community structure in the bio-production of VFAs from ES were
      investigated at different pH conditions. Denaturing gradient gel electrophoresis
      (DGGE) was performed to characterize the bacterial community structure of ES. The
      results showed that the optimal pH was 10.0 for VFA production, and acetic and
      propionic acids were the dominant acid species. Pseudomonas sp. was identified as
      the major bacteria capable of utilizing organic carbon at all pHs. Uncultured
      bacterium (AB658278) adapted well at high pH. Uncultured bacteria (KC633537 and
      JN596370) were mainly responsible for anaerobic degradation of ES. The study
      demonstrated the variation of bacterial community structures at pHs and the close
      correlation with the VFA accumulation.

PMID- 24291314
TI  - Biohydrogen production from sugarcane bagasse by integrating dark- and photo
      fermentation.
AB  - Hydrogen production from sugarcane bagasse (SCB) by integrating dark-fermentation
      by Enterobacter aerogenes MTCC 2822 and photo-fermentation by Rhodopseudomonas
      BHU 01 was investigated. The SCB was hydrolysed by sulphuric acid and the
      hydrolysate detoxified by passing through adsorbent resin column (Amberlite XAD
      4) to remove the inhibitory furfural, and subjected to dark-fermentation. The
      cellulosic residue from acid hydrolysis was hydrolysed by the new isolate
      Cellulomonas fimi to release sugars for H2 production by E. aerogenes, through
      simultaneous saccharification, filtration and fermentation (SSFF). Cumulative H2
      production during dark-fermentation and SSFF was 1000 and 613 ml/L, respectively.
      The spent media of dark-fermentation and SSFF were utilized for photo
      fermentation by Rhodopseudomonas BHU 01. The cumulative H2 production was 755
      ml/L for dark-fermentation and 351 ml/L for SSFF spent medium.

PMID- 24291315
TI  - Effects of chemical form of sodium on the product characteristics of alkali
      lignin pyrolysis.
AB  - The effects of Na as organic bound form or as inorganic salts form on the
      pyrolysis products characteristics of alkali lignin were investigated by using
      thermogravimetric analyzer coupled with Fourier transform infrared spectrometry
      (TG-FTIR), tube furnace and thermo-gravimetric analyzer (TGA). Results of TG-FTIR
      and tube furnace indicated that the two chemical forms Na reduced the releasing
      peak temperature of CO and phenols leading to the peak temperature of the maximum
      mass loss rate shifted to low temperature zone. Furthermore, organic bound Na
      obviously improved the elimination of alkyl substituent leading to the yields of
      phenol and guaiacol increased, while inorganic Na increased the elimination of
      phenolic hydroxyl groups promoting the formation of ethers. It was also found the
      two chemical forms Na had different effects on the gasification reactivity of
      chars. For inorganic Na, the char conversion decreased with increasing the char
      forming temperature, while organic bound Na was opposite. 

PMID- 24291316
TI  - Effect of outdoor conditions on Nannochloropsis salina cultivation in artificial
      seawater using nutrients from anaerobic digestion effluent.
AB  - The effects of simulated outdoor seasonal climatic conditions on Nannochloropsis
      salina (N. salina) grown using nutrients from anaerobic digestion (AD) effluent
      were evaluated in this study. Under various light exposure (LE) and temperature
      (10-30  degrees C) conditions, N. salina specific growth rate (MU) was strongly
      affected by LE. Light availability (LA) was observed to be crucial for biomass
      production, with MU values of 0.038+/-0.013 d(-1), 0.093+/-0.013 d(-1), and
      0.151+/-0.021 d(-1) for 6-h, 12-h, and 24-h LA conditions, respectively.
      Temperature (10-25  degrees C) was not significant in affecting the light
      dependent growth coefficient (MU/LE), indicating the suitability of culturing
      this strain in the Ohio climate. Cultures exposed to low illumination had
      significantly higher unsaturated fatty acid content than those under high
      illumination, with nearly 29% higher eicosapentaenoic acid (C20:5) content. Using
      LE and light attenuation resulted in adequate prediction of N. salina growth in a
      1000 L open raceway pond.

PMID- 24291317
TI  - Effects of pH and fermentation strategies on 2,3-butanediol production with an
      isolated Klebsiella sp. Zmd30 strain.
AB  - This study examined the effects of pH-controlled and fermentation strategies on
      2,3-butanediol (2,3-BDO) production by an isolated Klebsiella sp. Zmd30 strain.
      The pH value of 6.0 was found to be optimal among the investigated range of 4.5
      9.0. In batch fermentation, the concentration, productivity and yield of 2,3-BDO
      were 57.17 g/l, 1.59 g/l/h and 82%, respectively. The 2,3-BDO production by
      Klebsiella sp. Zmd30 was found to be growth-associated. Higher 2,3-BDO
      concentration (110 g/l) and yield (94%) was obtained by using fed-batch
      operation, but the productivity was lower (0.88 g/l/h) as compared to that when
      using batch operation. The highest 2,3-BDO productivity of 2.81 g/l/h was
      obtained with the continuous culture at a hydraulic retention time (HRT) of 12h.
      The results suggest that fed-batch operation might be most suitable for
      commercialized 2,3-BDO production, due to obtaining a high concentration and
      yield.

PMID- 24291319
TI  - Performance and microbial community of completely autotrophic nitrogen removal
      over nitrite (CANON) process in two membrane bioreactors (MBR) fed with different
      substrate levels.
AB  - To study the influence of substrate on completely autotrophic nitrogen removal
      over nitrite (CANON) process, two membrane bioreactors (MBR) with identical setup
      but fed with different substrate levels (R1 with low ammonia, R2 with high
      ammonia), were adopted in this study. The nitrogen removal performance,
      bioactivity, biodiversity and distribution of the functional microorganisms in
      two reactors were investigated. Both the aerobic ammonia-oxidizing bacteria
      (AerAOB) and anaerobic ammonia-oxidizing bacteria (AnAOB) in R2 showed higher
      bioactivity than those in R1, while nitrite-oxidizing bacteria (NOB) showed the
      contrary result. Nitrosomonas and Candidatus Kuenenia stuttgartiensis were
      detected as predominant functional microbes in the two reactors while Nitrobacter
      only existed in R1. High influent ammonia possibly led to the higher biodiversity
      of AerAOB and the more densely packed distribution. Meanwhile, this study has
      demonstrated the feasibility of increasing ammonia for rapid start-up, and
      decreasing HRT for high-rate nitrogen removal in CANON process. 

PMID- 24291318
TI  - Significance evaluation of the effects of environmental factors on the lipid
      accumulation of Chlorella minutissima UTEX 2341 under low-nutrition heterotrophic
      condition.
AB  - The effects of a variety of environmental factors on lipid accumulation of
      Chlorella minutissima UTEX 2341 under low-nutrition conditions were investigated.
      The growth of UTEX 2341 reached the exponential phase on the 1st day in low
      nutrition medium. And the highest biomass productivity of 3.07 g L(-1) d(-1) was
      achieved on the 2nd day. The optimum pH and temperature for lipid accumulation
      were 6 and 20  degrees C respectively. 43.69 g L(-1) of NaCl and 0.11 mmol L(-1)
      of Fe(III) resulted in higher lipid content, analyzed by Design-Expert. And then
      under nitrogen starvation stress, the lipid content reached 22.84%. Meanwhile,
      the lipid yield was 2.5 g L(-1). The yield coefficient against carbon was 0.36 g
      g(-1), which was 4.68 times as much as that in OM medium. With the high
      proportion of C16 and C18 in the lipids, C. minutissima UTEX 2341 was proved to
      be a potential option for renewable biodiesel production.

PMID- 24291320
TI  - Parasite-induced alteration of plastic response to predation threat: increased
      refuge use but lower food intake in Gammarus pulex infected with the
      acanothocephalan Pomphorhynchus laevis.
AB  - Larvae of many trophically-transmitted parasites alter the behaviour of their
      intermediate host in ways that increase their probability of transmission to the
      next host in their life cycle. Before reaching a stage that is infective to the
      next host, parasite larvae may develop through several larval stages in the
      intermediate host that are not infective to the definitive host. Early predation
      at these stages results in parasite death, and it has recently been shown that
      non-infective larvae of some helminths decrease such risk by enhancing the anti
      predator defences of the host, including decreased activity and increased
      sheltering. However, these behavioural changes may divert infected hosts from an
      optimal balance between survival and foraging (either seeking food or a mate). In
      this study, this hypothesis was tested using the intermediate host of the
      acanthocephalan parasite Pomphorhynchus laevis, the freshwater amphipod Gammarus
      pulex. We compared activity, refuge use, food foraging and food intake of hosts
      experimentally infected with the non-infective stage (acanthella), with that of
      uninfected gammarids. Behavioural assays were conducted in four situations
      varying in predation risk and in food accessibility. Acanthella-infected
      amphipods showed an increase in refuge use and a general reduction in activity
      and food intake. There was no effect of parasite intensity on these traits.
      Uninfected individuals showed plastic responses to water-borne cues from fish by
      adjusting refuge use, activity and food intake. They also foraged more when the
      food was placed outside the refuge. At the intra-individual level, refuge use and
      food intake were positively correlated in infected gammarids only. Overall, our
      findings suggest that uninfected gammarids exhibit risk-sensitive behaviour
      including increased food intake under predation risk, whereas gammarids infected
      with the non-infective larvae of P. laevis exhibit a lower motivation to feed,
      irrespective of predation risk and food accessibility. 

PMID- 24291321
TI  - Functional characterisation of a nicotinic acetylcholine receptor alpha subunit
      from the brown dog tick, Rhipicephalus sanguineus.
AB  - Ticks and tick-borne diseases have a major impact on human and animal health
      worldwide. Current control strategies rely heavily on the use of chemical
      acaricides, most of which target the CNS and with increasing resistance, new
      drugs are urgently needed. Nicotinic acetylcholine receptors (nAChRs) are targets
      of highly successful insecticides. We isolated a full-length nAChR alpha subunit
      from a normalised cDNA library from the synganglion (brain) of the brown dog
      tick, Rhipicephalus sanguineus. Phylogenetic analysis has shown this R.
      sanguineus nAChR to be most similar to the insect alpha1 nAChR group and has been
      named Rsanalpha1. Rsanalpha1 is distributed in multiple tick tissues and is
      present across all life-stages. When expressed in Xenopus laevis oocytes
      Rsanalpha1 failed to function as a homomer, with and without the addition of
      either Caenorhabditis elegans resistance-to-cholinesterase (RIC)-3 or X. laevis
      RIC-3. When co-expressed with chicken beta2 nAChR, Rsanalpha1 evoked
      concentration-dependent, inward currents in response to acetylcholine (ACh) and
      showed sensitivity to nicotine (100 MUM) and choline (100 MUM). Rsanalpha1/beta2
      was insensitive to both imidacloprid (100 MUM) and spinosad (100 MUM). The
      unreliable expression of Rsanalpha1 in vitro suggests that additional subunits or
      chaperone proteins may be required for more robust expression. This study
      enhances our understanding of nAChRs in arachnids and may provide a basis for
      further studies on the interaction of compounds with the tick nAChR as part of a
      discovery process for novel acaricides.

PMID- 24291323
TI  - Creative use of technology for distracting children for MRIs.

PMID- 24291322
TI  - Solution conformation of adenovirus virus associated RNA-I and its interaction
      with PKR.
AB  - Adenovirus virus-associated RNA (VAI) provides protection against the host
      antiviral response in part by inhibiting the interferon-induced double stranded
      RNA-activated protein kinase (PKR). VAI consists of three base-paired regions;
      the apical stem responsible for the interaction with double-stranded RNA binding
      motifs (dsRBMs) of PKR, the central stem required for inhibition, and the
      terminal stem. The solution conformation of VAI and VAI lacking the terminal stem
      were determined using SAXS that suggested extended conformations that are in
      agreement with their secondary structures. Solution conformations of VAI lacking
      the terminal stem in complex with the dsRBMs of PKR indicated that the apical
      stem interacts with both dsRNA-binding motifs whereas the central stem does not.
      Hydrodynamic properties calculated from ab initio models were compared to
      experimentally determined parameters for model validation. Furthermore, SAXS
      envelopes were used as a constraint for the in silico modeling of tertiary
      structure for RNA and RNA-protein complex. Finally, full-length PKR was also
      studied, but concentration-dependent changes in hydrodynamic parameters prevented
      ab initio shape determination. Taken together, results provide an improved
      structural framework that further our understanding of the role VAI plays in
      evading host innate immune responses. 

PMID- 24291324
TI  - The changing epidemiology of hepatitis C virus infection in the United States:
      National Health and Nutrition Examination Survey 2001 through 2010.
AB  - BACKGROUND & AIMS: In light of the dramatically changing hepatitis C therapeutic
      landscape, knowledge of the current burden of HCV infection in the general
      population of the United States is critical. METHODS: The National Health and
      Nutrition Examination survey collects nationally representative data on HCV
      infection in the civilian population of the United States. Data from 2001 to 2010
      were combined for this study. HCV testing was completed in 38,025 participants.
      RESULTS: The prevalence of anti-HCV in the United Sates decreased from 1.9% (95%
      CI 1.5%-2.5%) in 2001-2002 to 1.3% (95% CI 0.9%-1.8%) in 2005-2006, and remained
      stable up to 2010. About 67% of all infected persons were positive for HCV RNA,
      indicating 2.3 million people with chronic HCV infection, of whom 68% have
      genotype 1. Seventy percent of infected persons were born between 1945 and 1965,
      with prevalence of 3.5% (95% CI 2.2%-4.8%). The stable rate since 2006 is mostly
      related to prevalent cases and foreign born persons migrating into US. Other
      important risk factors include less education and low economic status. Race, HIV
      status, number of sexual partners, and blood transfusions are no longer
      associated with HCV infection. CONCLUSIONS: As of 2010, approximately 2.3 million
      persons were chronically infected with Hepatitis C in the US. Most of those
      infected are prevalent, rather than incident cases. The prevalence of HCV was on
      the decline, but has stabilized since 2006. Future studies should explore reasons
      for no decline in HCV prevalence since 2006.

PMID- 24291325
TI  - The effects of moderate exercise on chronic stress-induced intestinal barrier
      dysfunction and antimicrobial defense.
AB  - The purpose of this study was to examine the effect of moderate exercise on
      repeated restraint stress (RRS)-induced intestinal barrier dysfunction and
      explore possible mechanisms in a mouse model. Male Balb/c mice (6weeks) were
      randomized into 7 groups: CON functioned as controls with no intervention; RRS
      was subjected to 6h per day RRS for 7 consecutive days; RRS+SWIM received 30min
      per day of swimming prior to RRS; CON+SWIM only received 30min per day of
      swimming; and the other groups received one session of 30min swimming prior to
      sacrifice at 1-, 3- and 6h recovery. Intestinal permeability was quantified with
      FITC-dextran. Bacterial translocation was determined by quantification of
      bacterial colony forming units (CFUs) in cultured mesenteric lymph nodes (MLN),
      and with fluorescence in situ hybridization (FISH). Antimicrobial related gene
      expression at baseline and 1h after one session of 30min swimming was tested by
      quantitative real-time polymerase chain reaction (Q-PCR) in small intestinal
      segments. Protein expression of 5 genes with statistically significant increase
      was measured at baseline, and 1-, 3- and 6h post-swimming using enzyme-linked
      immunosorbent assay (ELISA). Thirty minutes per day of swimming before RRS
      attenuated bacterial translocations and maintained intestinal permeability. Gene
      expression and protein levels for four antimicrobial peptides (alpha-defensin 5,
      beta-defensin 1, RegIIIbeta and RegIIIgamma) were significantly increased after
      one 30min swimming session. In conclusion, moderate exercise attenuated chronic
      stress-induced intestinal barrier dysfunction in mice, possibly due to
      augmentation of antimicrobial responses in the small intestine. 

PMID- 24291326
TI  - Cholesterol acceptor capacity is preserved by different mechanisms in preterm and
      term fetuses.
AB  - Fetal serum cholesterol and lipoprotein concentrations differ between preterm and
      term born neonates. An imbalance of the flow of cholesterol from the sites of
      synthesis or efflux from cells of peripheral organs to the liver, the reverse
      cholesterol transport (RCT), is linked to atherosclerosis and cardiovascular
      disease (CVD). Preterm delivery is a risk factor for the development of CVD.
      Thus, we hypothesized that RCT is affected by a diminished cholesterol acceptor
      capacity in preterm as compared to term fetuses. Cholesterol efflux assays were
      performed in RAW264.7, HepG2, and HUVEC cell lines. In the presence and absence
      of ABC transporter overexpression by TO-901317, umbilical cord sera of preterm
      and term born neonates (n = 28 in both groups) were added. Lipid components
      including high density lipoprotein (HDL), low density lipoprotein (LDL),
      apolipoprotein A1, and apolipoprotein E were measured and related to fractional
      cholesterol efflux values. We found overall, fractional cholesterol efflux to
      remain constant between the study groups, and over gestational ages at delivery,
      respectively. However, correlation analysis revealed cholesterol efflux values to
      be predominantly related to HDL concentration at term, while in preterm neonates,
      cholesterol efflux was mainly associated with LDL In conclusion cholesterol
      acceptor capacity during fetal development is kept in a steady state with
      different mechanisms and lipid fractions involved at distinct stages during the
      second half of fetal development. However, RCT mechanisms in preterm neonates
      seem not to be involved in the development of CVD later in life suggesting rather
      changes in the lipoprotein pattern causative.

PMID- 24291328
TI  - Controlling initial biodegradation of magnesium by a biocompatible strontium
      phosphate conversion coating.
AB  - A simple strontium phosphate (SrP) conversion coating process was developed to
      protect magnesium (Mg) from the initial degradation post-implantation. The
      coating morphology, deposition rate and resultant phases are all dependent on the
      processing temperature, which determines the protective ability for Mg in minimum
      essential medium (MEM). Coatings produced at 80  degrees C are primarily made up
      of strontium apatite (SrAp) with a granular surface, a high degree of
      crystallinity and the highest protective ability, which arises from retarding
      anodic dissolution of Mg in MEM. Following 14 days' immersion in MEM, the SrAp
      coating maintained its integrity with only a small fraction of the surface
      corroded. The post-degradation effect of uncoated Mg and Mg coated at 40 and 80 
      degrees C on the proliferation and differentiation of human mesenchymal stem
      cells was also studied, revealing that the SrP coatings are biocompatible and
      permit proliferation to a level similar to that of pure Mg. The present study
      suggests that the SrP conversion coating is a promising option for controlling
      the early rapid degradation rate, and hence hydrogen gas evolution, of Mg
      implants without adverse effects on surrounding cells and tissues.

PMID- 24291329
TI  - Platelet-derived growth-factor-releasing aligned collagen-nanoparticle fibers
      promote the proliferation and tenogenic differentiation of adipose-derived stem
      cells.
AB  - In order to enhance the healing potential of an injured tendon, we have prepared
      a novel biomimetic aligned collagen-nanoparticle (NP) composite fiber using an
      electrochemical process. The aligned collagen-NP composite fiber is designed to
      affect the cellular activity of adipose-derived stem cells (ADSCs) through two
      different ways: (i) topographic cues from the alignment of collagen fibril and
      (ii) controlled release of platelet-derived growth factors (PDGFs) from the NPs.
      PDGF released from collagen-NP fibers significantly enhanced the proliferation of
      ADSCs when tested for up to 7 days. Moreover, compared to random collagen fibers
      with PDGFs, aligned collagen-NP fibers significantly promoted the desirable
      tenogenic differentiation of ADSCs, as evidenced by an increased level of tendon
      markers such as tenomodulin and scleraxis. On the other hand, no undesirable
      osteogenic differentiation, as measured by the unchanged level of alkaline
      phosphatase and osteocalcin, was observed. Together, these results indicate that
      the aligned collagen-NP composite fiber induced the tenogenic differentiation of
      ADSCs through both a topographic cue (aligned collagen fibril) and a chemical cue
      (PDGF released from NPs). Thus, our novel aligned collagen-NP composite fiber has
      a significant potential to be used for tendon tissue engineering and
      regeneration.

PMID- 24291327
TI  - Role of cholesterol sulfate in epidermal structure and function: lessons from X
      linked ichthyosis.
AB  - X-linked ichthyosis is a relatively common syndromic form of ichthyosis most
      often due to deletions in the gene encoding the microsomal enzyme, steroid
      sulfatase, located on the short area of the X chromosome. Syndromic features are
      mild or unapparent unless contiguous genes are affected. In normal epidermis,
      cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but
      desulfated in the outer epidermis, together forming a 'cholesterol sulfate cycle'
      that potently regulates epidermal differentiation, barrier function and
      desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid
      mass (~1% of total weight). Multiple cellular and biochemical processes
      contribute to the pathogenesis of the barrier abnormality and scaling phenotype
      in XLI. This article is part of a Special Issue entitled The Important Role of
      Lipids in the Epidermis and their Role in the Formation and Maintenance of the
      Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 24291330
TI  - Magic-angle spinning solid-state multinuclear NMR on low-field instrumentation.
AB  - Mobile and cost-effective NMR spectroscopy exploiting low-field permanent magnets
      is a field of tremendous development with obvious applications for arrayed large
      scale analysis, field work, and industrial screening. So far such demonstrations
      have concentrated on relaxation measurements and lately high-resolution liquid
      state NMR applications. With high-resolution solid-state NMR spectroscopy being
      increasingly important in a broad variety of applications, we here introduce low
      field magic-angle spinning (MAS) solid-state multinuclear NMR based on a
      commercial ACT 0.45 T 62 mm bore Halbach magnet along with a homebuilt FPGA
      digital NMR console, amplifiers, and a modified standard 45 mm wide MAS probe for
      7 mm rotors. To illustrate the performance of the instrument and address cases
      where the low magnetic field may offer complementarity to high-field NMR
      experiments, we demonstrate applications for (23)Na MAS NMR with enhanced second
      order quadrupolar coupling effects and (31)P MAS NMR where reduced influence from
      chemical shift anisotropy at low field may facilitate determination of
      heteronuclear dipole-dipole couplings.

PMID- 24291331
TI  - Phase reconstruction from velocity-encoded MRI measurements--a survey of sparsity
      promoting variational approaches.
AB  - In recent years there has been significant developments in the reconstruction of
      magnetic resonance velocity images from sub-sampled k-space data. While showing a
      strong improvement in reconstruction quality compared to classical approaches,
      the vast number of different methods, and the challenges in setting them up,
      often leaves the user with the difficult task of choosing the correct approach,
      or more importantly, not selecting a poor approach. In this paper, we survey
      variational approaches for the reconstruction of phase-encoded magnetic resonance
      velocity images from sub-sampled k-space data. We are particularly interested in
      regularisers that correctly treat both smooth and geometric features of the
      image. These features are common to velocity imaging, where the flow field will
      be smooth but interfaces between the fluid and surrounding material will be
      sharp, but are challenging to represent sparsely. As an example we demonstrate
      the variational approaches on velocity imaging of water flowing through a packed
      bed of solid particles. We evaluate Wavelet regularisation against Total
      Variation and the relatively recent second order Total Generalised Variation
      regularisation. We combine these regularisation schemes with a contrast
      enhancement approach called Bregman iteration. We verify for a variety of
      sampling patterns that Morozov's discrepancy principle provides a good criterion
      for stopping the iterations. Therefore, given only the noise level, we present a
      robust guideline for setting up a variational reconstruction scheme for MR
      velocity imaging. 

PMID- 24291332
TI  - Myasthenia gravis and thymoma coexisting with myotonic dystrophy type 1.
AB  - We describe a 34-year old man presenting with subacute generalized myasthenic
      symptoms. His clinical features and laboratory investigations demonstrated both
      myasthenia gravis and myotonic dystrophy type 1. The computerized tomography of
      chest revealed anterior mediastinal mass. The lymphocyte-rich thymoma was removed
      surgically and he received radiotherapy. Recent observations suggested that the
      patients with myotonic dystrophy may have an increased risk of benign and
      malignant tumours but its coexistence with thymoma is very rare. The risk of
      thymoma associated with myotonic dystrophy is unknown. 

PMID- 24291333
TI  - Round window membrane intracochlear drug delivery enhanced by induced advection.
AB  - Delivery of therapeutic compounds to the inner ear via absorption through the
      round window membrane (RWM) has advantages over direct intracochlear infusions;
      specifically, minimizing impact upon functional hearing measures. However,
      previous reports show that significant basal-to-apical concentration gradients
      occur, with the potential to impact treatment efficacy. Here we present a new
      approach to inner ear drug delivery with induced advection aiding distribution of
      compounds throughout the inner ear in the murine cochlea. Polyimide microtubing
      was placed near the RWM niche through a bullaostomy into the middle ear cavity
      allowing directed delivery of compounds to the RWM. We hypothesized that a
      posterior semicircular canalostomy would induce apical flow from the patent
      cochlear aqueduct to the canalostomy due to influx of cerebral spinal fluid. To
      test this hypothesis, young adult CBA/CaJ mice were divided into two groups:
      bullaostomy approach only (BA) and bullaostomy+canalostomy (B+C). Cochlear
      function was evaluated by distortion product otoacoustic emission (DPOAE) and
      auditory brainstem response (ABR) thresholds during and after middle ear infusion
      of salicylate in artificial perilymph (AP), applied near the RWM. The mice
      recovered for 1week, and were re-tested. The results demonstrate there was no
      significant impact on auditory function utilizing the RWM surgical procedure with
      or without the canalostomy, and DPOAE thresholds were elevated reversibly during
      the salicylate infusion. Comparing the threshold shifts for both methods, the B+C
      approach had more of a physiological effect than the BA approach, including at
      lower frequencies representing more apical cochlear locations. Unlike mouse
      cochleostomies, there was no deleterious auditory functional impact after 1week
      recovery from surgery. The B+C approach had more drug efficacy at lower
      frequencies, underscoring potential benefits for more precise control of delivery
      of inner ear therapeutic compounds. 

PMID- 24291334
TI  - Cell experimental studies on sonoporation: state of the art and remaining
      problems.
AB  - Sonoporation is the formation of transient pores on cell membrane by ultrasound
      exposure. Sonoporation can be applied to the increasing delivery of drug or gene
      into cells. However, there are some problems encountered in sonoporation studies.
      The mechanisms to produce sonoporation are very complicated; there are too many
      experimental parameters affecting the sonoporation results; and there are many
      bio-effects accompanied with sonoporation. In the article, the cell experimental
      studies on sonoporation were sorted, including experimental methods, mechanisms
      to produce sonoporation, correlations between sonoporation experimental
      parameters and results, and bioeffects accompanied with sonoporation. We'd like
      to make the concepts about sonoporation clearer. The sonoporation technology may
      be a promising auxiliary technology to promote drug or gene therapy in the
      future. 

PMID- 24291335
TI  - Recent progress of cell-penetrating peptides as new carriers for intracellular
      cargo delivery.
AB  - The plasma membrane as a selectively permeable barrier of living cells is
      essential to cell survival and function. In many cases, however, the efficient
      passage of exogenous bioactive molecules through the plasma membrane remains a
      major hurdle for intracellular delivery of cargoes. During the last two decades,
      the potential of peptides for drug delivery into cells has been highlighted by
      the discovery of numerous cell-penetrating peptides (CPPs). CPPs serving as
      carriers can successfully intracellular transport cargoes such as siRNA, nucleic
      acids, proteins, small molecule therapeutic agents, quantum dots and MRI contrast
      agents. This review mainly introduces recent advances of CPPs as new carriers for
      the development of cellular imaging, nuclear localization, pH-sensitive and
      thermally targeted delivery systems. In particular, we highlight the exploiting
      of the synergistic effects of targeting ligands and CPPs. What's more, the
      classification and cellular uptake mechanisms of CPPs are briefly discussed as
      well. 

PMID- 24291336
TI  - Pain and cooperation in patients having dominant-side or nondominant-side
      phacoemulsification.
AB  - PURPOSE: To evaluate the relationship between laterality and perceived pain and
      cooperation during phacoemulsification under combined topical and intracameral
      anesthesia. SETTING: University ophthalmology clinic and eye hospital,
      Kahramanmaras, Turkey. DESIGN: Cohort study. METHODS: Seventy-eight patients with
      senile cataracts who had ocular surgery were included prospectively. The dominant
      side was determined with the Edinburg Handedness Inventory. Phacoemulsification
      and intraocular lens implantation were performed. The surgeon graded the
      patient's cooperation from 0 (best) to 3 (worst). The duration of surgery was
      recorded. Another researcher rated perceived pain from 0 (no pain) to 10
      (unbearable pain) using a visual analogue scale (VAS). Pain scores and the degree
      of cooperation for dominant-side and nondominant-side surgery were the primary
      outcomes. RESULTS: Forty-six patients had surgery in the dominant eye and 32 in
      the nondominant eye. The 2 groups were similar in age, sex, and severity and type
      of cataract. The mean VAS score was significantly higher in patients having
      dominant-side surgery than in those having nondominant-side surgery (P<.01).
      Similarly, the mean cooperation score was significantly poorer in the patients
      having dominant-side surgery (P<.05). Visual analogue scores were correlated with
      patient cooperation (r = 0.890, P<.0001). CONCLUSION: Pain scores were higher in
      dominant-side surgery for cataract under topical and intracameral anesthesia,
      which should be kept in mind when selecting anesthesia and in studies in which
      pain is scored. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24291337
TI  - Restriction of the Xenopus DEADSouth mRNA to the primordial germ cells is ensured
      by multiple mechanisms.
AB  - DEADSouth mRNA encoding the RNA helicase DDX25 is a component of the germ plasm
      in Xenopus laevis. We investigated the mechanisms underlying its specific mRNA
      expression in primordial germ cells (PGCs). Based on our previous findings of
      several microRNA miR-427 recognition elements (MREs) in the 3' untranslated
      region of the mRNA, we first examined whether DEADSouth mRNA was degraded by miR
      427 targeting in somatic cells. Injection of antisense miR-427 oligomer and
      reporter mRNA for mutated MREs revealed that DEADSouth mRNA was potentially
      degraded in somatic cells via miR-427 targeting, but not in PGCs after the mid
      blastula transition (MBT). The expression level of miR-427 was very low in PGCs,
      which probably resulted in the lack of miR-427-mediated degradation. In addition,
      the DEADSouth gene was expressed zygotically after MBT. Thus, the predominant
      expression of DEADSouth mRNA in the PGCs is ensured by multiple mechanisms
      including zygotic expression and prohibition from miR-427-mediated degradation. 

PMID- 24291338
TI  - Nonstationary multivariate modeling of cerebral autoregulation during
      hypercapnia.
AB  - We examined the time-varying characteristics of cerebral autoregulation and
      hemodynamics during a step hypercapnic stimulus by using recursively estimated
      multivariate (two-input) models which quantify the dynamic effects of mean
      arterial blood pressure (ABP) and end-tidal CO2 tension (PETCO2) on middle
      cerebral artery blood flow velocity (CBFV). Beat-to-beat values of ABP and CBFV,
      as well as breath-to-breath values of PETCO2 during baseline and sustained euoxic
      hypercapnia were obtained in 8 female subjects. The multiple-input, single-output
      models used were based on the Laguerre expansion technique, and their parameters
      were updated using recursive least squares with multiple forgetting factors. The
      results reveal the presence of nonstationarities that confirm previously reported
      effects of hypercapnia on autoregulation, i.e. a decrease in the MABP phase lead,
      and suggest that the incorporation of PETCO2 as an additional model input yields
      less time-varying estimates of dynamic pressure autoregulation obtained from
      single-input (ABP-CBFV) models.

PMID- 24291339
TI  - Cognitive flexibility depends on white matter microstructure of the basal
      ganglia.
AB  - Ample evidence shows that the basal ganglia play an important role in cognitive
      flexibility. However, traditionally, cognitive processes have most commonly been
      associated with the prefrontal cortex. Indeed, current theoretical models of
      basal ganglia function suggest the basal ganglia interact with the prefrontal
      cortex and thalamus, via anatomical fronto-striato-thalamic circuits, to
      implement cognitive flexibility. Here we aimed to assess this hypothesis in
      humans by associating individual differences in cognitive flexibility with white
      matter microstructure of the basal ganglia. To this end we employed an attention
      switching paradigm in adults with ADHD and controls, leading to a broad range in
      task performance. Attention switching performance could be predicted based on
      individual differences in white matter microstructure in/around the basal
      ganglia. Crucially, local white matter showing this association projected to
      regions in the prefrontal cortex and thalamus. Our findings highlight the crucial
      role of the basal ganglia and the fronto-striato-thalamic circuit for cognitive
      flexibility. 

PMID- 24291341
TI  - Estimating the decline in excess risk of cerebrovascular disease following
      quitting smoking--a systematic review based on the negative exponential model.
AB  - We attempted to quantify the decline in stroke risk following quitting using the
      negative exponential model, with methodology previously employed for IHD. We
      identified 22 blocks of RRs (from 13 studies) comparing current smokers, former
      smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases
      and controls/at risk formed the data for model-fitting. We tried to estimate the
      half-life (H, time since quit when the excess risk becomes half that for a
      continuing smoker) for each block. The method failed to converge or produced very
      variable estimates of H in nine blocks with a current smoker RR <1.40. Rejecting
      these, and combining blocks by amount smoked in one study where problems arose in
      model-fitting, the final analyses used 11 blocks. Goodness-of-fit was adequate
      for each block, the combined estimate of H being 4.78(95%CI 2.17-10.50) years.
      However, considerable heterogeneity existed, unexplained by any factor studied,
      with the random-effects estimate 3.08(1.32-7.16). Sensitivity analyses allowing
      for reverse causation or differing assumed times for the final quitting period
      gave similar results. The estimates of H are similar for stroke and IHD, and the
      individual estimates similarly heterogeneous. Fitting the model is harder for
      stroke, due to its weaker association with smoking. 

PMID- 24291340
TI  - Electrophysiological evidence for speech-specific audiovisual integration.
AB  - Lip-read speech is integrated with heard speech at various neural levels. Here,
      we investigated the extent to which lip-read induced modulations of the auditory
      N1 and P2 (measured with EEG) are indicative of speech-specific audiovisual
      integration, and we explored to what extent the ERPs were modulated by phonetic
      audiovisual congruency. In order to disentangle speech-specific (phonetic)
      integration from non-speech integration, we used Sine-Wave Speech (SWS) that was
      perceived as speech by half of the participants (they were in speech-mode), while
      the other half was in non-speech mode. Results showed that the N1 obtained with
      audiovisual stimuli peaked earlier than the N1 evoked by auditory-only stimuli.
      This lip-read induced speeding up of the N1 occurred for listeners in speech and
      non-speech mode. In contrast, if listeners were in speech-mode, lip-read speech
      also modulated the auditory P2, but not if listeners were in non-speech mode,
      thus revealing speech-specific audiovisual binding. Comparing ERPs for
      phonetically congruent audiovisual stimuli with ERPs for incongruent stimuli
      revealed an effect of phonetic stimulus congruency that started at ~200 ms after
      (in)congruence became apparent. Critically, akin to the P2 suppression,
      congruency effects were only observed if listeners were in speech mode, and not
      if they were in non-speech mode. Using identical stimuli, we thus confirm that
      audiovisual binding involves (partially) different neural mechanisms for sound
      processing in speech and non-speech mode.

PMID- 24291342
TI  - Comparison of several functional methods to evaluate the immune response on
      stable kidney transplant patients.
AB  - The introduction of new immunosuppressive drugs in the last two decades has been
      associated with a significant decline in the prevalence of acute rejection and a
      huge improvement of graft survival. Monitoring blood levels of immunosuppressive
      drugs is the most common way to control drug doses in renal transplant patients.
      This approach is useful and widely used but doesn't give accurate information
      about the immune status of the patient. For this goal, there are many "in house"
      protocols which give more information, but cannot be standardized, limiting their
      applicability to compare results between different laboratories. In this study we
      compare three classical functional methods to evaluate the immune response: Mixed
      lymphocyte reaction (MLR), phytohemagglutinin stimulated peripheral blood
      lymphocytes (PBLs), and anti-CD3 monoclonal antibodies (mAbs) against PBL with
      the only FDA-labeled assay to measure the patient immune status: Cylex
      ImmuKnow(r) that measures the intracelullar ATP in CD4+ lymphocytes. We used
      n=111 stable renal transplant patients, all the patients with more than one year
      functioning grafts. We referred the results to a control population of healthy
      blood donors (n=125). RESULTS: Measurement of intracellular ATP in CD4+
      lymphocytes is able to differentiate immunosuppressed populations in renal
      transplant patients from health controls (242.30+/-21.62 vs. 386.43+/-25.12, p
      0.0001). By contrary, there were no differences between controls and renal
      recipients when functional response was measured by MLR, PHA and anti-CD3 mAbs
      (2.48+/-0.45 vs. 2.37+/-0.41; 2.84+/-0.76 vs. 2.37+/-0.32; 2.32+/-0.34 vs. 1.89+/
      0.38 respectively). In summary, our results show that the measurement of ATP in
      CD4+ lymphocytes gives more accurate information in comparison to the classical
      methods.

PMID- 24291343
TI  - Characterization and validation of new tools for measuring site-specific cardiac
      troponin I phosphorylation.
AB  - Phosphorylation of cardiac troponin I is a well established mechanism by which
      cardiac contractility is modulated. However, there are a number of
      phosphorylation sites on TnI which contribute singly or in combination to
      influence cardiac function. Accordingly, methods for accurately measuring site
      specific TnI phosphorylation are needed. Currently, two strategies are employed:
      mass spectrometry, which is costly, difficult and has a low throughput; and
      Western blotting using phospho-specific antibodies, which is limited by the
      availability of reagents. In this report, we describe a cohort of new site
      specific TnI phosphoantibodies, generated against physiologically relevant
      phosphorylation sites, that are superior to the current commercially available
      antibodies: to phospho-serine 22/23 which shows a >5-fold phospho-specificity for
      phosphorylated TnI; to phospho-serine 43, which has >3-fold phospho-specificity
      for phosphorylated TnI; and phospho-serine 150 which has >2-fold phospho
      specificity for phosphorylated TnI. These new antibodies demonstrated greater
      sensitivity and specificity for the phosphorylated TnI than the most widely used
      commercially available reagents. For example, at a protein load of 20 MUg of
      total cardiac extract, a commercially available antibody recognized both
      phosphorylated and dephosphorylated TnI to the same degree. At the same protein
      load our phospho-serine 22/23 antibody exhibited no cross-reactivity with
      dephosphorylated TnI. These new tools should allow a more accurate assessment and
      a better understanding of the role of TnI phosphorylation in the response of the
      heart to pathologic stress.

PMID- 24291344
TI  - A His6-SUMO-eXact tag for producing human prepro-urocortin 2 in Escherichia coli
      for raising monoclonal antibodies.
AB  - This is a first report of recombinant production of human prepro-Urocortin 2 in
      Escherichia coli by N-terminal fusion with a triple His6-SUMO-eXact tag and its
      subsequent use as an antigen for the production and screening of very high
      affinity monoclonal antibodies. The rationale for this combinatorial construct is
      that the His tag allows first step protein purification of insoluble and soluble
      proteins, the SUMO tag enhances protein expression level and solubility, while
      the eXact tag facilitates anion-triggered on-column cleavage of the triple tag to
      recover pure native proteins in a simple two-step protein purification procedure.
      Compared with an eXact fusion alone, the presence of the SUMO moiety enhanced
      overall expression levels by 4 to 10 fold but not the solubility of the highly
      basic prepro-Urocortin 2. Insoluble SUMO-eXact-preproUCN2 was purified in
      milligram quantities by denaturing IMAC and solubilized in native phosphate
      buffer by on-column refolding or step-wise dialysis. Only a small fraction of
      this solubilized protein was able to bind onto the eXactTM affinity column and
      cleaved by NaF treatment. To test whether binding and cleavage failure was due to
      improperly refolded SUMO-eXact-preproUCN2 or to the presence of N- and C-terminal
      sequences flanking the eXact moiety, we created a SUMO-eXact-thioredoxin
      construct which was overexpressed mainly in the soluble form. This protein bound
      to and was cleaved efficiently on the eXactTM column to yield native thioredoxin.
      Solubilized SUMO-eXact-preproUCN2 was used successfully to generate two high
      affinity mouse monoclonal antibodies (KD~10-10 and 10-11 M) specific to the pro
      region of Urocortin 2.

PMID- 24291346
TI  - An efficient and reproducible process for transmission electron microscopy (TEM)
      of rare cell populations.
AB  - Transmission electron microscopy (TEM) provides ultra-structural details of cells
      at the sub-organelle level. However, details of the cellular ultrastructure, and
      the cellular organization and content of various organelles in rare populations,
      particularly in the suspension, like hematopoietic stem cells (HSCs) remained
      elusive. This is mainly due to the requirement of millions of cells for TEM
      studies. Thus, there is a vital requirement of a method that will allow TEM
      studies with low cell numbers of such rare populations. We describe an
      alternative and novel approach for TEM studies for rare cell populations. Here we
      performed a TEM study from 10,000 HSC cells with relative ease. In particular,
      tiny cell pellets were identified by Evans blue staining after PFA-GA fixation.
      The cell pellet was pre-embedded in agarose in a small microcentrifuge tube and
      processed for dehydration, infiltration and embedding. Semi-thin and ultra-thin
      sections identified clusters of numerous cells per sections with well preserved
      morphology and ultrastructural details of golgi complex and mitochondria.
      Together, this method provides an efficient, easy and reproducible process to
      perform qualitative and quantitative TEM analysis from limited biological samples
      including cells in suspension. 

PMID- 24291345
TI  - Optimization and validation of the TZM-bl assay for standardized assessments of
      neutralizing antibodies against HIV-1.
AB  - The TZM-bl assay measures antibody-mediated neutralization of HIV-1 as a function
      of reductions in HIV-1 Tat-regulated firefly luciferase (Luc) reporter gene
      expression after a single round of infection with Env-pseudotyped viruses. This
      assay has become the main endpoint neutralization assay used for the assessment
      of pre-clinical and clinical trial samples by a growing number of laboratories
      worldwide. Here we present the results of the formal optimization and validation
      of the TZM-bl assay, performed in compliance with Good Clinical Laboratory
      Practice (GCLP) guidelines. The assay was evaluated for specificity, accuracy,
      precision, limits of detection and quantitation, linearity, range and robustness.
      The validated manual TZM-bl assay was also adapted, optimized and qualified to an
      automated 384-well format. 

PMID- 24291348
TI  - Turning it off.

PMID- 24291347
TI  - Disability associated with obesity, dynapenia and dynapenic-obesity in Chinese
      older adults.
AB  - OBJECTIVES: Whether the combination of obesity and low muscle strength (dynapenic
      obesity) would cause greater impairment of the activities of daily living
      (ADL)/instrumental activities of daily living (IADL) than obesity alone and low
      muscle strength alone (dynapenia) remains unclear. The aim of this study was to
      reveal the possible independent and additive effects of dynapenia and obesity on
      ADL/IADL disability in an older Chinese population. METHODS: A cross-sectional
      study, including 616 community-dwelling older adults, was conducted in China from
      2010 to 2012. Based on the World Health Organization Asian Criteria of Obesity
      and handgrip strength tertiles, 4 independent groups were identified as follows:
      nondynapenia/nonobesity, dynapenia alone, obesity alone, and dynapenic-obesity.
      The Katz Index of Independence in ADL was used to assess ADL disability, whereas
      6 IADL items of the Older Americans Resources and Services (OARS)
      multidimensional functional assessment questionnaire were used to assess IADL
      disability. RESULTS: The prevalence of ADL and IADL disability was 21.1% and
      28.9% in the dynapenic-obesity group, 15.5% and 22.6% in the dynapenia alone
      group, 13.1% and 19.6% in the obesity alone group, and 11.9% and 12.9% in the
      nondynapenia/nonobesity group, respectively. After adjusting for the covariates,
      in comparison with the dynapenic-obesity group, the adjusted odds ratios (95%
      confidence interval) for ADL disability were 0.36 (0.13-0.73) in the
      nondynapenia/nonobesity group, 0.51 (0.20-0.78) in the dynapenia-alone group, and
      0.40 (0.11-0.61) in the obesity-alone group. The corresponding data for IADL
      disability were 0.55 (0.20-0.93), 0.82 (0.39-0.98), and 0.61 (0.30-0.91),
      respectively. CONCLUSION: Dynapenia, obesity, and dynapenic-obesity were
      associated with an increased risk of ADL/IADL disability. Dynapenic-obesity was
      associated with a greater risk of ADL/IADL disability in comparison with
      dynapenia or obesity alone.

PMID- 24291349
TI  - Fairness as partiality aversion: the development of procedural justice.
AB  - Adults and children dislike inequity-people being paid unequally for equal work.
      However, adults will allow inequity if the inequity is determined using an
      impartial procedure, indicating that they value procedural justice. It is unknown
      whether children value procedural justice when distributing resources. We
      investigated whether 5- to 8-year-old children would willingly create inequity
      between two recipients if they could do so using an impartial procedure. In
      Experiment 1, children preferred to use an impartial procedure (spinning a wheel
      that gave both recipients an equal chance to get a resource) over a partial
      procedure (spinning a wheel that gave one recipient a much better chance to get
      the resource). In Experiments 2 and 3, children preferred to use the same
      impartial procedure to assign a resource to one of two recipients, even over an
      option of keeping things equal by throwing the resource in the trash.
      Importantly, children preferred to throw the resource in the trash to uphold
      equality when the only other option was a partial procedure. Older children
      showed a stronger aversion to using partial procedures than younger children.
      These results suggest that children value procedural justice increasingly during
      middle childhood and that their fairness concerns may be more about avoiding
      partiality than inequity per se. 

PMID- 24291350
TI  - Reprint of "In utero exposure to benzo[a]pyrene increases adiposity and causes
      hepatic steatosis in female mice, and glutathione deficiency is protective".
AB  - Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are
      ubiquitous environmental pollutants found in tobacco smoke, air pollution, and
      grilled foods. Reactive metabolites and reactive oxygen species generated during
      PAH metabolism are detoxified by reactions involving glutathione (GSH). Early
      life exposures to tobacco smoke and air pollution have been linked to increased
      risk of obesity and metabolic syndrome. We investigated the independent and
      interactive effects of prenatal exposure to BaP and GSH deficiency due to
      deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate
      limiting enzyme in GSH synthesis, on adiposity and hepatic steatosis in adult
      female F1 offspring. We mated Gclm(+/-) dams with Gclm(+/-) males and treated the
      pregnant dams with 0, 2, or 10 mg/kg/day BaP in sesame oil by oral gavage daily
      from gestational day 7 through 16. We analyzed metabolic endpoints in female
      Gclm(-/-) and Gclm(+/+) littermate F1 offspring. Prenatal BaP exposure
      significantly increased visceral adipose tissue weight, weight gain between 3
      weeks and 7.5 months of age, hepatic lipid content measured by oil red O
      staining, and hepatic fatty acid beta-oxidation gene expression in Gclm(+/+), but
      not in Gclm(-/-), female offspring. Hepatic expression of lipid biosynthesis and
      antioxidant genes were decreased and increased, respectively, in Gclm(-/-) mice.
      Our results suggest that reported effects of pre- and peri-natal air pollution
      and tobacco smoke exposure on obesity may be mediated in part by PAHs. GSH
      deficiency is protective against the metabolic effects of prenatal BaP exposure.

PMID- 24291352
TI  - Automation of the radiosynthesis and purification procedures for [18F]Fluspidine
      preparation, a new radiotracer for clinical investigations in PET imaging of
      sigma(1) receptors in brain.
AB  - The radiosynthesis of [(18)F]Fluspidine, a potent sigma1 receptor imaging probe
      for pre-clinical/clinical studies, was implemented on a TRACERlab(TM) FX F-N
      synthesizer. [(18)F]2 was synthesized in 15 min at 85  degrees C starting from
      its tosylate precursor. Purification via semi-preparative RP-HPLC was
      investigated using different columns and eluent compositions and was most
      successful on a polar RP phase with acetonitrile/water buffered with NH4OAc.
      After solid phase extraction, [(18)F]Fluspidine was formulated and produced
      within 59+/-4 min with an overall radiochemical yield of 37+/-8%, a radiochemical
      purity of 99.3+/-0.5% and high specific activity (176.6+/-52.0 GBq/umol).

PMID- 24291351
TI  - High plasma levels of vitamin C and E are associated with incident radiographic
      knee osteoarthritis.
AB  - BACKGROUND: Previous studies suggest that the antioxidants vitamins C and E may
      protect against development of knee osteoarthritis (OA). We examined the
      association of circulating levels of vitamin C and E with incident whole knee
      radiographic OA (WKROA). METHODS: We performed a nested case-control study of
      incident WKROA in MOST, a cohort of 3,026 men and women aged 50-79 years with, or
      at high risk of, knee OA. Incident cases were knees without either tibiofemoral
      (TF) or patellofemoral (PF) OA at baseline that developed TF and/or PF OA by 30
      month follow-up. Two control knees per case were selected from those eligible for
      WKROA that did not develop it. Vitamin C and E (alpha-tocopherol) assays were
      done on baseline supernatant plasma (PCA) and serum samples, respectively. We
      examined the association of gender-specific tertiles of vitamin C and E with
      incident WKROA using logistic regression with GEE, adjusting for age, gender, and
      obesity. RESULTS: Subjects without WKROA at baseline who were in the highest
      tertile of vitamin C had a higher incidence of WKROA [adjusted OR = 2.20 (95% CI:
      1.12-4.33); P-value = 0.021], with similar results for the highest tertile of
      vitamin E [adjusted OR = 1.89 (1.02-3.50); P-value = 0.042], compared to those in
      the lowest tertiles. P-values for the trend of vitamin C and E tertiles and
      incident WKROA were 0.019 and 0.030, respectively. CONCLUSIONS: Higher levels of
      circulating vitamin C and E did not provide protection against incident
      radiographic knee OA, and may be associated with an increased risk of knee OA.

PMID- 24291353
TI  - Proteomics identifies the composition and manufacturing recipe of the 2500-year
      old sourdough bread from Subeixi cemetery in China.
AB  - We report on the geLC-MS/MS proteomics analysis of cereals and cereal food
      excavated in Subeixi cemetery (500-300BC) in Xinjiang, China. Proteomics provided
      direct evidence that at the Subexi sourdough bread was made from barley and
      broomcorn millet by leavening with a renewable starter comprising baker's yeast
      and lactic acid bacteria. The baking recipe and flour composition indicated that
      barley and millet bread belonged to the staple food already in the first
      millennium BC and suggested the role of Turpan basin as a major route for
      cultural communication between Western and Eastern Eurasia in antiquity. This
      article is part of a Special Issue entitled: Proteomics of non-model organisms.
      BIOLOGICAL SIGNIFICANCE: We demonstrate that organic residues of thousand year
      old foods unearthed by archeological excavations can be analyzed by geLC-MS/MS
      proteomics with good representation of protein source organisms and coverage of
      sequences of identified proteins. In-depth look into the foods proteome
      identifies the food type and its individual ingredients, reveals ancient food
      processing technologies, projects their social and economic impact and provides
      evidence of intercultural communication between ancient populations. Proteomics
      analysis of ancient organic residues is direct, quantitative and informative and
      therefore has the potential to develop into a valuable, generally applicable tool
      in archaeometry. This article is part of a Special Issue entitled: Proteomics of
      non-model organisms.

PMID- 24291356
TI  - Stereoselective facile synthesis of 2'-spiro pyrimidine pyranonucleosides via
      their key intermediate 2'-C-cyano analogues. Evaluation of their bioactivity.
AB  - A novel series of 2'-spiro pyrimidine pyranonucleosides has been designed and
      synthesized. Their precursors, 2'-C-cyano nucleosides 5a,b and 6a,b, were
      obtained by subjecting 1a,b to the sequence of selective protection of the
      primary hydroxyl group, acetalation, oxidation, and finally treatment with sodium
      cyanide. Deoxygenation at the 2'-position of cyanohydrins 5a,b or 6a,b led to the
      2'-deoxy derivatives 9a,b. Fully deprotection of 5a,b, 6a,b, and 9a,b gave the
      desired 2'-C-cyano 7a,b, 8a,b, and 2'-C-cyano-2'-deoxy pyranonucleosides 10a,b,
      respectively. Mesylation of the corresponding cyanohydrins 5a,b and 6a,b afforded
      compounds 11a,b and 12a,b which after base treatment and subsequent deprotection
      furnished the spiro nucleosides 15a,b and 16a. The new analogues were evaluated
      for their potential cytostatic activities in cell culture. 

PMID- 24291357
TI  - Synthesis and conformational analysis of phosphorylated beta-(1->2) linked
      mannosides.
AB  - Phosphorylated beta-(1->2)-oligomannosides are found on the cell surface of
      several Candida species, including Candida albicans (an opportunistic pathogen).
      These molecules are believed to take part in the invasion process of fungal
      infections, which in the case of C. albicans can lead to severe bloodstream
      infections and death, and can therefore be considered important from a biological
      standpoint. Understanding the mechanism of their action requires access to the
      corresponding oligosaccharide model compounds in pure form. In the present work,
      synthesis of the model core structures involved in the invasion process of C.
      albicans, consisting of phosphorylated beta-(1->2)-linked mannotriose and
      tetraose, is reported. In order to elucidate the nature of these molecules in
      more detail, an extensive NMR-spectroscopic study encompassing complete spectral
      characterization, conformational analysis and molecular modelling was performed.
      The obtained results were also compared to similar chemical entities devoid of
      the charged phosphate group. 

PMID- 24291358
TI  - Sodium selenite treatment restores long-lasting ovarian damage induced by
      irradiation in rats: impact on oxidative stress and apoptosis.
AB  - The deleterious damage of reproductive function following radiotherapy is of
      increasing importance. In the present study, we investigated the impact of long
      term sodium selenite (SS) treatment on radiotherapy-induced ovarian injury in a
      rat model. Two-week after radiation exposure vaginal cyclicity was arrested, and
      serum FSH level was elevated in irradiated female rats. SS significantly
      ameliorated ovarian and uterine oxidative stress induced by irradiation through
      decreasing the lipid peroxide level and increasing the glutathione level, and
      glutathione peroxidase activity. In the presence of SS, ovarian cytochrome c and
      caspase 3 expressions triggered by radiotherapy were decreased. SS significantly
      counteracted radiation-induced a widespread loss of ovarian follicles and caused
      further stimulation of follicular proliferation through enhancing PCNA
      expression. Despite such alteration in ovarian function, serum estradiol level
      did not change after irradiation, whereas SS significantly increased it. In
      conclusion, long-term SS treatment improved reproductive development, which was
      impaired by radiotherapy. 

PMID- 24291354
TI  - A possible role of transglutaminase 2 in the nucleus of INS-1E and of cells of
      human pancreatic islets.
AB  - Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent
      transamidating and G protein activity. Previously we reported that the role of
      TG2 in insulin secretion may involve cytoplasmic actin remodeling and a
      regulative action on other proteins during granule movement. The aim of this
      study was to gain a better insight into the role of TG2 transamidating activity
      in mitochondria and in the nucleus of INS-1E rat insulinoma cell line (INS-1E)
      during insulin secretion. To this end we labeled INS-1E with an artificial donor
      (biotinylated peptide), in basal condition and after stimulus with glucose for 2,
      5, and 8min. Biotinylated proteins of the nuclear/mitochondrial-enriched fraction
      were analyzed using two-dimensional electrophoresis and mass spectrometry. Many
      mitochondrial proteins involved in Ca(2+) homeostasis (e.g. voltage-dependent
      anion-selective channel protein, prohibitin and different ATP synthase subunits)
      and many nuclear proteins involved in gene regulation (e.g. histone H3, barrier
      to autointegration factor and various heterogeneous nuclear ribonucleoprotein)
      were identified among a number of transamidating substrates of TG2 in INS-1E. The
      combined results provide evidence that a temporal link exists between glucose
      stimulation, first phase insulin secretion and the action of TG on histone H3
      both in INS-1E and human pancreatic islets. BIOLOGICAL SIGNIFICANCE: Research
      into the role of transglutaminase 2 during insulin secretion in INS-1E rat
      insulinoma cellular model is depicting a complex role for this enzyme.
      Transglutaminase 2 acts in the different INS-1E compartments in the same way:
      catalyzing a post-translational modification event of its substrates. In this
      work we identify some mitochondrial and nuclear substrates of INS-1E during first
      phase insulin secretion. The finding that TG2 interacts with nuclear proteins
      that include BAF and histone H3 immediately after (2-5min) glucose stimulus of
      INS-1E suggests that TG2 may be involved not only in insulin secretion, as
      suggested by our previous studies in cytoplasmic INS-1E fraction, but also in the
      regulation of glucose-induced gene transcription.

PMID- 24291355
TI  - A new biomarker of hedonic eating? A preliminary investigation of cortisol and
      nausea responses to acute opioid blockade.
AB  - Overweight and obese individuals differ in their degree of hedonic eating. This
      may reflect adaptations in reward-related neural circuits, regulated in part by
      opioidergic activity. We examined an indirect, functional measure of central
      opioidergic activity by assessing cortisol and nausea responses to acute opioid
      blockade using the opioid antagonist naltrexone in overweight/obese women (mean
      BMI=31.1+/-4.8) prior to the start of a mindfulness-based intervention to reduce
      stress eating. In addition, we assessed indices of hedonic-related eating,
      including eating behaviors (binge eating, emotional eating, external eating,
      restraint) and intake of sweets/desserts and carbohydrates (Block Food
      Frequency); interoceptive awareness (which is associated with dysregulated eating
      behavior); and level of adiposity at baseline. Naltrexone-induced increases in
      cortisol were associated with greater emotional and restrained eating and lower
      interoceptive awareness. Naltrexone-induced nausea was associated with binge
      eating and higher adiposity. Furthermore, in a small exploratory analysis,
      naltrexone-induced nausea predicted treatment response to the mindfulness
      intervention, as participants with more severe nausea at baseline maintained
      weight whereas those with little or no nausea responses tended to gain weight.
      These preliminary data suggest that naltrexone-induced cortisol release and
      nausea may help identify individuals who have greater underlying food reward
      dependence, which leads to an excessive drive to eat. Future research is needed
      to confirm this finding and to test if these markers of opioidergic tone might
      help predict success in certain types of weight management programs. 

PMID- 24291359
TI  - Neuroforaminal chondrocyte metaplasia and clustering associated with recombinant
      bone morphogenetic protein-2 usage in transforaminal lumbar interbody fusion.
AB  - BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is
      commonly used to augment posterior and interbody spinal fusion techniques and has
      many reported side effects. Neuroforaminal heterotopic ossification (HO) is a
      known cause of postoperative leg pain, but the pathohistologic composition of
      this material is not well understood. PURPOSE: The purpose of this article was to
      report the histologic composition of a case of HO and lumbar radiculopathy after
      transforaminal lumbar interbody fusion with rhBMP-2. STUDY DESIGN/SETTING: This
      is a case report. PATIENT SAMPLE: This is a single patient case report. OUTCOME
      MEASURES: The outcomes considered were physician-recorded clinical,
      physiological, and functional measures. METHODS: A retrospective review of a
      single patient was performed. Clinical, radiographic, and pathologic specimens
      were reviewed and are reported. RESULTS: A 69-year-old woman presented with low
      back pain and right leg radicular pain associated with L4-L5 stenosis and a
      recurrent facet cyst. After attempted nonsurgical care, she underwent an L4-L5
      revision decompression with interbody and posterolateral fusions including off
      label rhBMP-2. Postoperatively, her symptoms resolved for approximately 7 months
      but then returned in association with right L4-L5 foraminal HO. The ectopic
      tissue was notably larger than suggested by preoperative computed tomographic
      scan. It was decompressed, which then improved her symptoms. Histologic
      examination of the specimen revealed three discrete tissue types: a nonspecific
      fibrovascular stroma; immature osteoid and woven bone; and chondrocyte metaplasia
      with chondrocyte clustering. CONCLUSIONS: Neuroforaminal HO formation is a
      reported side effect associated with the off-label use of rhBMP-2 for posterior
      lumbar interbody fusion. The mechanism of formation and the composition of this
      material are not well understood but may involve a chondrocyte differentiation
      pathway.

PMID- 24291360
TI  - Neural reflex pathway between cervical spinal and sympathetic ganglia in rabbits:
      implication for pathogenesis of cervical vertigo.
AB  - BACKGROUND CONTEXT: A functional association between cervix and vertigo has been
      observed in patients with cervical vertigo, implicating correlation between
      cervical spinal and sympathetic ganglia. However, it is unclear where there is an
      anatomic connection between those two groups of ganglia. PURPOSE: This study
      aimed to investigate the existence of the neural connections between cervical
      spinal and sympathetic ganglia. STUDY DESIGN/SETTING: FluoroGold staining
      patterns in cervical spinal and sympathetic ganglia were evaluated using
      FluoroGold retrograde tracing in New Zealand rabbits. METHODS: New Zealand
      rabbits were randomly divided into superior cervical spinal ganglion injection
      groups, inferior cervical spinal ganglion injection groups, superior cervical
      sympathetic ganglion injection group, and inferior cervical sympathetic ganglion
      injection group. Four percent FluoroGold solution was injected into these
      ganglia. Distribution of FluoroGold in cervical spinal and sympathetic ganglia
      was observed under a microscope. RESULTS: When FluoroGold solution was injected
      into C2 and C3 superior cervical spinal ganglia or C5-C6 inferior cervical spinal
      ganglia, fluorescence was only observed in the ipsilateral superior or inferior
      cervical sympathetic ganglia, respectively. When FluoroGold solution was injected
      into superior or inferior cervical sympathetic ganglia, fluorescence was found
      mainly in the ipsilateral C3-C4 superior or C5-C8 inferior spinal ganglia. No
      fluorescence was observed in contralateral ganglia of experimental animals and
      all ganglia of matched control animals injected with physiological saline.
      CONCLUSIONS: Bidirectional nerve fiber connections between cervical spinal and
      sympathetic ganglia were observed, and these connections are arranged in a
      segmental distribution. This observation may provide a possible neuroanatomic
      basis for the pathogenesis of cervical vertigo.

PMID- 24291361
TI  - Enhancing DNA delivery into the skin with a motorized microneedle device.
AB  - The purpose of this study was to evaluate a motorized microneedle device in
      delivery of DNA into skin for gene expression. A plasmid DNA encoding both
      luciferase (Luc) and enhanced green fluorescent protein (EGFP) was delivered into
      rat skin by puncturing the skin with the microneedle device. Puncturing rat skin
      with a pre-applied DNA solution on the skin showed much higher luciferase gene
      expression than that with the procedure of puncturing the skin first then applied
      the DNA solution. The microneedle puncturing method was more efficient than
      intradermal injection method in generating high gene expression in the skin.
      There was no significant difference in the skin gene expression when rat skin was
      punctured with the microneedle device of different microneedle lengths (0.25 mm,
      0.5mm or 0.75 mm). On the other hand, there was a significant difference in the
      skin gene expression between the short (10s) and the long puncturing durations
      (30 or 60s), with longer puncturing duration showed higher gene expression.
      Puncturing the skin with longer needles (0.75 mm) caused some skin damage, while
      puncturing the skin with shorter microneedle length (0.25 mm) caused only minimal
      skin damage. The EGFP gene expression was observed predominately in the epidermis
      layer of the skin from the puncturing method in delivery of DNA into the skin. In
      summary, the motorized microneedle device could have great potential in skin gene
      delivery.

PMID- 24291362
TI  - Commentary on the article by Swanenburg et al. 'Validity and reliability of a
      German version of the Neck Disability Index (NDI-G)' [Man Ther Articles in Press
      http://dx.doi.org/10.1016/j.math.2013.07.004].

PMID- 24291363
TI  - Acute effects of rearfoot manipulation on dynamic standing balance in healthy
      individuals.
AB  - Dynamic standing balance is essential to perform functional activities and is
      included in the treatment of many lower extremity injuries. Physiotherapists
      utilize many methods to restore standing balance including stability exercises,
      functional retraining, and manual therapy. The purpose of this study was to
      investigate the effects of a rearfoot distraction manipulation on dynamic
      standing balance. Twenty healthy participants (age: 24.4 +/- 2.8 years; height:
      162.9 +/- 37.7 cm; mass: 68.0 +/- 4.8 kg; right leg dominant = 20) completed this
      study. Following familiarization, dynamic standing balance was assessed during:
      (1) an experimental condition immediately following a rearfoot distraction
      manipulation, and (2) a control condition. Dominant leg balance was quantified
      using the Y-balance test which measures lower extremity reach distances. Reach
      distances were normalized to leg length and measured in the anterior,
      posteromedial and posterolateral directions. Overall balance was calculated
      through the summing of all normalized directions. Paired t-tests and Wilcoxon
      rank tests were used to compare balance scores for parametric and non-parametric
      data as appropriate. Significance was set at 0.05 a priori. Effect size (ES) was
      calculated to determine the clinical impact of the manipulation. Increased reach
      distances (indicating improved balance) were noted following manipulation for
      overall balance (p = 0.03, ES = 0.26) and in the posteromedial direction (p =
      0.01, ES = 0.42). Reach distances did not differ for the anterior (p = 0.11, ES =
      0.16) or posterolateral (p = 0.11, ES = 0.25) components. Dynamic standing
      balance improved after a rearfoot distraction manipulation in healthy
      participants. It is hypothesized that manual therapy applied to the foot and
      ankle may be beneficial to augment other therapeutic modalities when working with
      patients to improve dynamic standing balance.

PMID- 24291364
TI  - Do neck kinematics correlate with pain intensity, neck disability or with fear of
      motion?
AB  - PURPOSE: This study aimed to investigate the relationship between cervical
      kinematics and subjective measures, including pain intensity, disability, and
      fear of motion. METHODS: Twenty-five patients (19 females, 6 males; mean age 39
      +/- 12.7 years) with chronic neck pain participated in this cross-sectional
      study. A customized virtual reality system was employed to evaluate cervical
      range of motion (ROM) and kinematics, using an interactive game controlled by
      cervical motion via electromagnetic tracking. Self-reported outcome measures
      included pain intensity (visual analogue scale); disability (Neck Disability
      Index); and fear of motion (TAMPA scale of kinesiophobia). Kinematic measures
      included cervical ROM, mean and peak velocity, and number of velocity peaks (NVP)
      reflecting smoothness of motion. RESULTS: Results showed significant correlations
      of approximately 0.4-0.6 between ROM and fear of motion, pain intensity, and
      disability. All 12 kinematic measures were correlated with fear of motion, but
      only a few were correlated with pain intensity, and with disability. CONCLUSIONS:
      The results emphasise fear of motion as a subjective measure primarily correlated
      with neck kinematics, including range, velocity, and smoothness of cervical
      motion. The level of neck disability was found to be partly related to ROM or to
      other kinematic impairments. However, ROM by itself remains a valid measure
      related to pain intensity and to fear of motion in patients with chronic neck
      pain. All correlations demonstrated were moderate, indicating that these measures
      involve other factors in need of further research.

PMID- 24291365
TI  - Liver adapts mitochondrial function to insulin resistant and diabetic states in
      mice.
AB  - BACKGROUND & AIMS: To determine if diabetic and insulin-resistant states cause
      mitochondrial dysfunction in liver or if there is long term adaptation of
      mitochondrial function to these states, mice were (i) fed with a high-fat diet to
      induce obesity and T2D (HFD), (ii) had a genetic defect in insulin signaling
      causing whole body insulin resistance, but not full blown T2D (IR/IRS-1(+/-)
      mice), or (iii) were analyzed after treatment with streptozocin (STZ) to induce a
      T1D-like state. METHODS: Hepatic lipid levels were measured by thin layer
      chromatography. Mitochondrial respiratory chain (RC) levels and function were
      determined by Western blot, spectrophotometric, oxygen consumption and proton
      motive force analysis. Gene expression was analyzed by real-time PCR and
      microarray. RESULTS: HFD caused insulin resistance and hepatic lipid
      accumulation, but RC was largely unchanged. Livers from insulin resistant IR/IRS
      1(+/-) mice had normal lipid contents and a normal RC, but mitochondria were less
      well coupled. Livers from severely hyperglycemic and hypoinsulinemic STZ mice had
      massively depleted lipid levels, but RC abundance was unchanged. However, liver
      mitochondria isolated from these animals showed increased abundance and activity
      of the RC, which was better coupled. CONCLUSIONS: Insulin resistance, induced
      either by obesity or genetic manipulation and steatosis do not cause
      mitochondrial dysfunction in mouse liver. Also, mitochondrial dysfunction is not
      a prerequisite for liver steatosis. However, severe insulin deficiency and high
      blood glucose levels lead to an enhanced performance and better coupling of the
      RC. This may represent an adaptation to fuel overload and the high energy
      requirement of an unsuppressed gluconeogenesis.

PMID- 24291366
TI  - Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of
      variceal hemorrhage: a multicentre randomized controlled trial.
AB  - BACKGROUND & AIMS: Esophageal variceal bleed is a major problem in patients with
      cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or
      better than propranolol in preventing first bleed. Carvedilol is a non-selective
      beta blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have
      shown carvedilol to be more effective than propranolol at reducing portal
      pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of
      esophageal variceal bleed. METHODS: Cirrhotic patients with esophageal varices
      were randomized to carvedilol 12.5mg daily or EVL at three university hospitals
      of Pakistan. End points were esophageal variceal bleeding, death or liver
      transplant. RESULTS: Two hundred and nine patients were evaluated. Eighty two and
      eighty six patients were randomized in carvedilol and EVL arms respectively. Mean
      age was 48 +/- 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis;
      mean Child-Pugh score was 7.3 +/- 1.6 and mean follow up was 13.3 +/- 12.1 months
      (range 1-50 months). Both EVL and carvedilol groups had comparable variceal
      bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and
      overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol
      group were hypotension (n=2), requiring cessation of therapy, while transient
      nausea (n=18) and dyspnea (n=30) resolved spontaneously. In the EVL arm, post
      banding ulcer bleed (n=1) and chest pain (n=17), were termed as serious adverse
      events while transient dysphagia (n=58) resolved without treatment. CONCLUSIONS:
      Although our study is underpowered, the findings suggest that carvedilol is
      probably not superior to EVL in preventing first variceal bleed in patients with
      viral cirrhosis.

PMID- 24291367
TI  - Gain of long tonic immobility behavioral trait causes the red flour beetle to
      reduce anti-stress capacity.
AB  - Tonic immobility (death-feigning) behavior of the red flour beetle, Tribolium
      castaneum, is a predator defense mechanism; it is a reflex elicited when a beetle
      is jarred with the substrate, often a result of the activities of a predator. We
      previously demonstrated that the frequency of predation by a jumping spider,
      Hasarius adansoni, was significantly lower among beetles with higher frequencies
      and longer durations of tonic immobility (L-type) than those with lower
      frequencies and shorter durations of tonic immobility (S-type). However, we found
      that the population of L-type beetles is much smaller than that of S-type beetles
      in their natural habitat. Here we demonstrated that L-type beetles are
      significantly more sensitive to environmental stressors such as mechanical
      vibration and high or low temperatures. We measured expression levels of stress
      responsive genes such as heat shock proteins (Hsps) and antioxidant enzymes in
      both types of beetles. Among the genes we investigated, only catalase gene
      expression levels were significantly higher in S-type than in L-type beetles.
      Furthermore, a similar difference in the gene expression was observed in the T.
      castaneum ortholog of the insect cytokine growth-blocking peptide (GBP) gene.
      These results indicate the possibility that high expression of catalase and GBP
      in S-type beetles contributes to augmentation of their anti-stress capacity and
      expansion of their population in their natural habitat. 

PMID- 24291368
TI  - Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and
      tissue histopathology during co-exposure to arsenic-dichlorvos in rats.
AB  - We investigated protective efficacy of alpha-lipoic acid (LA), an antioxidant
      against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of
      oxidative stress, neurological dysfunction, and tissue histopathological
      alterations were determined. Male rats were exposed either to 50 ppm sodium
      arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously)
      for 10 weeks. alpha-Lipoic acid (50mg/kg, pos) was also co-administered in above
      groups. Arsenic exposure led to significant oxidative stress along,
      hepatotoxicity, hematotoxicity and altered brain biogenic amines levels
      accompanied by increased arsenic accumulation in blood and tissues. These altered
      biochemical variables were supported by histopathological examinations leading to
      oxidative stress and cell death. These biochemical alterations were significantly
      restored by co-administration of alpha-lipoic acid with arsenic and DDVP alone
      and concomitantly. The results indicate that arsenic and DDVP induced oxidative
      stress and cholinergic dysfunction can be significantly protected by the
      supplementation of alpha-lipoic acid.

PMID- 24291369
TI  - Comparison of embryo toxicity using two classes of aquatic vertebrates.
AB  - Toxicity tests of musk ketone (MK) and tetrabromobisphenol-A (TBBPA) on embryos
      were conducted in two amphibian species, Xenopus (Silurana) tropicalis and the
      Swedish native species Rana arvalis. TBBPA was also tested on fish embryos of
      Danio rerio. All species were tested in similar experimental setup. Musk ketone
      caused decreased heart rates at concentrations from 10 and 100 MUg/L in R.
      arvalis and X. tropicalis, respectively. TBBPA caused effects at 1000 MUg/L in
      all three species. The responses were comparable between all three species which
      supports the relevance for using data from non-native species in national risk
      assessment.

PMID- 24291370
TI  - Advances in deep brain stimulation for Parkinson disease: early and "asleep"?

PMID- 24291371
TI  - Endothelial-mesenchymal transition in cerebral cavernous malformations and the
      unveiling of new potential therapeutic targets.

PMID- 24291372
TI  - "Ex nihilo nihil fit": massive funding promises a golden decade of functional
      brain research.

PMID- 24291373
TI  - Studying obsessive-compulsive disorder using light.

PMID- 24291374
TI  - Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic
      value in Chinese breast cancer.
AB  - The prognostic significance of preoperative carcinoembryonic antigen (CEA) and
      cancer antigen 15-3 (CA15-3) levels in breast cancer is controversial. This study
      evaluated the prognostic value of preoperative serum CEA and CA15-3 levels in
      Chinese breast cancer patients. A total of 470 patients with breast cancer had
      preoperative CEA and CA15-3 concentrations measured. The relationships between
      preoperative concentration and clinicopathological factors and outcomes were
      determined. CEA and CA15-3 levels were increased in 34 (7.2%) and 58 (12.3%)
      patients, respectively. Elevations of serum CEA and CA-15-3 levels correlated
      with the primary tumor size and axillary lymph node status. CEA levels were lower
      in patients with triple-negative breast cancer than in those with other subtypes
      (P = 0.002). The 5-year distant metastasis-free survival (DMFS), disease-free
      survival (DFS), and overall survival (OS) of CEA-negative vs. CEA-positive
      patients were 84.1% vs. 54.5% (P < 0.001), 82.7% vs. 54.8% (P < 0.001), and 89.7%
      vs. 78.5% (P = 0.007), respectively. The 5-year DMFS, DFS, and OS of CA15-3
      negative vs. CA15-3-positive patients were 84.0% vs. 69.6% (P = 0.002), 83.0% vs.
      66.2% (P < 0.001), 90.9% vs. 74.2% (P = 0.005), respectively. Multivariate
      analysis of prognosis indicated that CEA and CA15-3 levels were independent
      prognostic factors for DMFS (P = 0.021) and DFS (P = 0.032), and DFS (P = 0.014)
      and OS (P = 0.032), respectively. Serum levels of CEA and CA15-3 may differ in
      breast cancer molecular subtypes and preoperative levels of CEA and CA15-3 have a
      significant effect on prognosis in Chinese women with breast cancer. 

PMID- 24291375
TI  - MarginProbe(r)--final results of the German post-market study in breast
      conserving surgery of ductal carcinoma in situ.
AB  - The goal in breast conserving surgery (BCS) of ductal carcinoma in situ (DCIS) is
      removal of the tumor with a clear surgical margin. However, re-excision rates are
      regrettably high. To date, there are no adequate procedures for intraoperative
      margin assessment of DCIS. A multicenter, single arm study was conducted to
      evaluate the benefit of a novel device (MarginProbe(r)) in intraoperative margin
      assessment during BCS of DCIS, the associated reduction of re-excisions and the
      cosmetic outcome of the treated patients. We present results of 42 patients
      enrolled in 3 German institutions. The device was used as an adjunctive tool to
      standard of care. The device use was associated with a reduction in re-excision
      rates by 56%, from 39% to 17% (p = 0.018).

PMID- 24291376
TI  - Time trends and inter-hospital variation in treatment and axillary staging of
      patients with ductal carcinoma in situ of the breast in the era of screening in
      Southern Netherlands.
AB  - BACKGROUND: To examine variation in time and place in axillary staging and
      treatment of patients with ductal carcinoma in situ (DCIS) of the breast.
      METHODS: Trends in patients with DCIS recorded in the Eindhoven Cancer Registry
      diagnosed in 1991-2010 (n = 2449) were examined. RESULTS: The use of breast
      conserving surgery (BCS) went from 17% to 67% in 1991-2010 and administration of
      radiotherapy after BCS increased to 89%. Axillary lymph node dissection decreased
      to almost 0%, while sentinel node biopsy was performed in 65% of patients in
      2010. The proportion who underwent BCS varied between hospitals from 49% to 80%;
      the proportion without axillary staging ranged from 21% to 60%. Patients with
      screen-detected DCIS were more likely to receive BCS. CONCLUSION: There was
      considerable variation in the use of BCS, radiotherapy, and axillary staging of
      DCIS over time and between hospitals. Patients with DCIS were more likely to be
      treated with BCS if their disease was detected by screening.

PMID- 24291377
TI  - Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery
      from type 2 diabetic OLETF rat at chronic stage of disease.
AB  - AIMS: There is a growing body of evidence suggesting that epigallocatechin
      gallate (EGCG), a major catechin isolated from green tea, has several beneficial
      effects, such as anti-oxidant and anti-inflammatory activities. However, whether
      treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in
      carotid arteries from type 2 diabetic rats is unknown, especially at the chronic
      stage of the disease. We hypothesized that long-term treatment with EGCG would
      attenuate ET-1-induced contractions in type 2 diabetic arteries. MAIN METHODS:
      Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with
      EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1,
      phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was
      measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF
      rats and control Long-Evans Tokushima Otsuka (LETO) rats. KEY FINDINGS: In OLETF
      rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups.
      However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In
      endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in
      either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by
      EGCG treatment in CA from the OLETF group. The expressions of ET receptors,
      endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an
      NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either
      group. SIGNIFICANCE: Our data suggest that, within the timescale investigated
      here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats,
      and one of the mechanisms may involve normalizing endothelial function.

PMID- 24291378
TI  - Evaluating radiotherapy options in breast cancer: does intraoperative
      radiotherapy represent the most cost-efficacious option?
AB  - INTRODUCTION: This study analyzed the cost-efficacy of intraoperative radiation
      therapy (IORT) compared with whole-breast irradiation (WBI) and accelerated
      partial-breast irradiation (APBI) for early-stage breast cancer. MATERIALS AND
      METHODS: Data for this analysis came from 2 phase III trials: the TARGIT
      (Targeted Intraoperative Radiotherapy) trial and the ELIOT (Electron
      Intraoperative Radiotherapy) trial. Cost analyses included a cost-minimization
      analysis and an incremental cost-effectiveness ratio analysis including a quality
      adjusted life-year (QALY) analysis. Cost analyses were performed comparing IORT
      with WBI delivered using 3-dimensional conformal radiotherapy (3D-CRT), APBI 3D
      CRT, APBI delivered with intensity-modulated radiotherapy (IMRT), APBI single
      lumen (SL), APBI multilumen (ML), and APBI interstitial (I). RESULTS: Per 1000
      patients treated, the cost savings with IORT were $3.6-$4.3 million, $1.6-$2.4
      million, $3.6-$4.4 million, $7.5-$8.2 million, and $2.8-$3.6 million compared
      with WBI 3D-CRT, APBI IMRT, APBI SL, APBI ML, and APBI I, respectively, with a
      cost decrement of $1.6-$2.4 million compared with APBI 3D-CRT based on data from
      the TARGIT trial. The costs per QALY for WBI 3D-CRT, APBI IMRT, APBI SL, APBI ML,
      and APBI I compared with IORT were $47,990-$60,002; $17,335-$29,347; $49,019
      $61,031; $108,162-$120,173; and $36,129-$48,141, respectively, based on data from
      the ELIOT trial. These results are consistent with APBI and WBI being cost
      effective compared with IORT. CONCLUSION: Based on cost-minimization analyses,
      IORT represents a potential cost savings in the management of early-stage breast
      cancer. However, absolute reimbursement is misleading, because when additional
      medical and nonmedical costs associated with IORT are factored in, WBI and APBI
      represent cost-effective modalities based on cost-per-QALY analyses. They remain
      the standard of care.

PMID- 24291379
TI  - Is there a tradeoff in using modified high tangent field radiation for treating
      an undissected node-positive axilla?
AB  - INTRODUCTION: Recent data are changing axillary management in patients with 1 to
      2 positive sentinel nodes. The proposed omission of completion axillary node
      dissection calls into question the need for axillary nodal irradiation. This
      study evaluates the difference in dose to the lung and heart and risk of
      radiation pneumonitis (RP) for patients treated with standard tangent fields
      (STF) compared with modified high tangent fields (MHTF). MATERIALS AND METHODS:
      Plans of 30 patients treated with STF were evaluated. A second plan (MHTF) was
      developed to include axillary levels I (Ax1) and II (Ax2). Ax1 and Ax2 volumes
      were contoured based on the RTOG (Radiation Therapy Oncology Group) Atlas
      guidelines. Dose-volume histograms of the 2 plans were used to compare doses
      received by Ax1, Ax2, lung, and heart volumes. The risk of RP was calculated
      using normal tissue complication probability (NTCP) modeling. RESULTS: The D95
      (dose to 95% of volume) received by Ax1 and Ax2 volumes increased from 16.38 Gy
      and 5.71 Gy for STF to 49.38 Gy and 48.08 Gy for MHTF, respectively. Mean lung
      dose increased from 5.40 Gy for STF to 9.47 Gy for MHTF. Mean ipsilateral lung
      V5, V10, and V20 values increased from 19%, 14%, and 10%, respectively, for STF,
      to 32%, 24%, and 18%, respectively, for MHTF. Mean heart dose increased from 1.98
      Gy for STF to 3.93 Gy for MHTF. Mean heart V25 and V30 values increased from 2%
      and 1%, respectively, for STF, to 4% and 3%, respectively, for MHTF. NTCP for RP
      increased from near 0% for STF to 1% for MHTF. CONCLUSION: Modified high tangent
      fields are necessary for definitive coverage of Ax1 and Ax2. This technique
      increases mean ipsilateral lung and heart doses as well as the V5, V10, and V20
      of ipsilateral lung and the V25 and V30 of the heart. Risk of RP remains low by
      use of MHTF.

PMID- 24291380
TI  - The effect of aromatase inhibition on the cognitive function of older patients
      with breast cancer.
AB  - INTRODUCTION: This study evaluated the association between aromatase inhibitor
      (AI) therapy and cognitive function (over a 6-month period) in a cohort of
      patients aged >= 60 years compared with an age-matched healthy control group, and
      it evaluated changes in regional cerebral metabolism as measured by positron
      emission tomography (PET) scans of the brain done in a subset of the patient
      cohort. PATIENTS AND METHODS: Thirty-five patients (32 evaluable) and 35 healthy
      controls were recruited to this study. Patients with breast cancer completed a
      neuropsychological battery, self-reported memory questionnaire, and geriatric
      assessment before initiation of AI therapy and again 6 months later. Age-matched
      healthy control participants completed the same assessments at the same time
      points as the patient group. RESULTS: No significant decline in cognitive
      function was seen among individuals receiving an AI from pretreatment to 6 months
      later compared with healthy controls. In the PET cohort over the same period,
      both standardized volume of interest and statistical parametric mapping analyses
      detected specific changes in metabolic activity between baseline and follow-up
      uniquely in the AI patients, most significantly in the medial temporal lobes.
      CONCLUSION: Although patients undergoing AI treatment had few changes in
      neuropsychological performance compared with healthy controls over a 6-month
      period, regionally specific changes in cerebral metabolic activity were
      identified during this interval in the patient group. Additional longitudinal
      follow-up is needed to understand the potential clinical implications of these
      findings.

PMID- 24291382
TI  - The effects of juvenile capsaicin desensitization in rats: behavioral
      impairments.
AB  - Capsaicin desensitization leads to behavioral changes, some of which are related
      to schizophrenia, but investigations into these effects have been scarce. The
      goal of this study was to characterize the consequences of juvenile capsaicin
      desensitization on different functions: acute and inflammation-induced thermal
      and mechanical sensitivity, urinary bladder capacity and thermoregulation, and
      also on the potentially schizophrenia-related impairments in sensory-motor
      gating, motor activity and cognitive functioning. Male Wistar rats desensitized
      with increasing doses of subcutaneous capsaicin after weaning were investigated.
      Heat and mechanical pain sensitivity did not change significantly; however,
      morphine produced a prolonged decrease in the nociceptive response to
      inflammation in desensitized animals. Ultrasound examination of the bladder
      revealed enhanced bladder volume in treated animals. Capsaicin-treated animals
      had higher body temperature at 22  degrees C in both dark and light periods, and
      they also showed prolonged hyperthermia in new environmental circumstances. Warm
      environment induced a profound impairment of thermoregulation in desensitized
      animals. The treated animals also showed higher levels of activity during the
      active phase and at both cool and warm temperatures. The amplitude of the
      responses to auditory stimuli and prepulse inhibition did not differ between the
      two groups, but the desensitized animals showed learning impairments in the novel
      object recognition test. These results suggest that juvenile capsaicin
      desensitization leads to sustained changes in several functions that may be
      related to schizophrenia. We propose that capsaicin desensitization, together
      with other interventions, may lead to an improved chronic animal model of
      schizophrenia.

PMID- 24291383
TI  - Time-dependent analysis of nociception and anxiety-like behavior in rats
      submitted to persistent inflammation of the temporomandibular joint.
AB  - Temporomandibular disorder (TMD) is prevalent in dental clinics and can involve
      problems with the masticatory muscles or the temporomandibular joints (TMJ). The
      pain of TMD is frequently associated with inflammation in the TMJs, but it's
      etiology is considered to be multifactorial and includes biologic, behavioral,
      environmental, social, emotional and cognitive factors. The purpose of this
      investigation was to evaluate the anxiety-like behavior in rats exposed to
      temporomandibular inflammation via injection of Freund's Adjuvant (CFA) with the
      elevated plus maze (EPM) and light/dark box (LDB) tests and to evaluate
      nociceptive behavior with the von Frey test at different periods. Moreover, this
      study measured TMJ inflammation using plasma extravasation (Evans blue test) and
      the intraarticular infiltration of polymorphonuclear neutrophils (myeloperoxidase
      quantification). The results showed that rats that were submitted to TMJ
      inflammation exhibited a decreased number of entries into the open arms of the
      EPM and a decrease in the time spent in the light compartment and in the number
      of transitions in the LDB. Additionally, the number of entries in closed arms in
      the EPM, used as indicator of locomotor activity, did not alter between
      treatments. Furthermore, increases in mechanical sensitivity and increases in
      plasma extravasation in the joint tissue occurred throughout the inflammation
      process, along with an increase in myeloperoxidase in the synovial fluid of TMJ.
      Our results suggest that the temporomandibular inflammation induced by CFA
      produced anxiety-like behaviors in rats and induced nociceptive behavior across
      different periods of inflammation. 

PMID- 24291381
TI  - Enhanced sympathetic activity in mice with brown adipose tissue transplantation
      (transBATation).
AB  - Brown adipose tissue (BAT) burns calories to produce heat, and is thus relevant
      to energy balance. Interscapular BAT (IBAT) of donor mice was transplanted into
      recipient mice (transBATation). To test whether transBATation counteracts high
      fat diet (HFD)-induced obesity, some sham-operated and recipient mice were fed a
      HFD (HFD-sham, HFD-trans) while others remained on a standard chow (chow-sham,
      chow-trans). HFD-trans mice had lower body weight and fat and greater energy
      expenditure, but similar caloric intake compared with HFD-sham mice. We
      hypothesized that HFD-trans mice had elevated sympathetic activity compared with
      HFD-sham mice, contributing to increased energy expenditure and fuel
      mobilization. This was supported by findings that HFD-trans mice had greater
      energy expenditure during a norepinephrine challenge test and higher core
      temperatures after cold exposure than did HFD-sham mice, implicating enhanced
      whole-body metabolic response and elevated sympathetic activity. Additionally,
      transBATation selectively increased sympathetic drive to some, but not all, white
      adipose tissue depots and skeletal muscles, as well as the endogenous IBAT,
      heart, and liver. Collectively, transBATation confers resistance to HFD-induced
      obesity via increase in whole-body sympathetic activity, and differential
      activation of sympathetic drive to some of the tissues involved in energy
      expenditure and fuel mobilization. 

PMID- 24291385
TI  - Sensorimotor cortex ablation induces time-dependent response of ACTH cells in
      adult rats: behavioral, immunohistomorphometric and hormonal study.
AB  - Traumatic brain injury (TBI) represents a serious event with far reaching
      complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH
      cells), that represent the active module of hypothalamo-pituitary-adrenocortical
      axis, seem to be affected as well. Since pituitary failure after TBI has been
      associated with neurobehavioral impairments the aim of this study was to evaluate
      the effects of TBI on recovery of motor functions, morphology and secretory
      activity of ACTH cells in the pituitary of adult rats. Wistar male rats,
      initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the
      2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to
      evaluate the recovery of motor functions. Pituitary glands and blood were
      collected for morphological and hormonal analyses. During the first two weeks
      post-injury increased recovery of locomotor function was detected, reaching
      almost the control value at day 30. SCA induces significant increase of pituitary
      weights compared to their time-matched controls. The volume of ACTH
      immunopositive cells was reduced at the 7th dps, while at the 14th dps their
      volume was enlarged, in comparison to corresponding sham controls. Volume density
      of ACTH cells was increased only at 14th dps, while at day 30 this increase was
      insignificant. The plasma level of ACTH transiently increased after the injury.
      The most pronounced changes were observed at the 7th and 14th dps, and were
      followed by decrease toward control levels at the 30th dps. Thus, temporal
      changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury
      appear to correlate with the recovery process.

PMID- 24291384
TI  - Comparison of brain urocortin-3 and corticotrophin-releasing factor for
      physiological responses in chicks.
AB  - Corticotrophin-releasing hormone (CRH) plays an important role in response to
      stress, and exerts a physiological effect via its receptor, CRH receptor type-1
      (CRH-R1) and CRH receptor type-2 (CRH-R2) with high affinity to CRH-R1 in
      mammals. Urocortin-3 (UCN-3), a CRH family peptide, is an endogenous ligand for
      CRH-R2 in mammals. The physiological roles of UCN-3 and CRH-R2 have been
      investigated in mammals, although their roles still need to be clarified in
      chicks (Gallus gallus). Few studies have been performed comparing the
      physiological responses of CRH and UCN-3 in chicks. Therefore the present study
      was conducted to investigate the effect of intracerebroventricular (ICV)
      injection of UCN-3 on food intake, rectal temperature, crop-emptying rate and
      behaviors in chicks, and to compare these physiological responses with the
      effects resulting from CRH injection. The ICV injection of 20 and 80 pmol UCN-3
      decreased food intake, increased rectal temperature and decreased crop-emptying
      rate and the results were similar to those achieved with CRH. The injection of
      both UCN-3 and CRH increased spontaneous activity but the behavioral patterns
      were different: CRH increased the number of vocalizations while UCN-3 increased
      the number of jumps, wing-flaps and scratching behaviors. These results suggest
      that UCN-3 regulates food intake, body temperature, and gastric emptying via the
      CRH-R2 in the brain of chicks, and these effects were similar to those induced by
      CRH.

PMID- 24291386
TI  - Cardiac autonomic modulation and sleepiness: physiological consequences of sleep
      deprivation due to 40 h of prolonged wakefulness.
AB  - The autonomic nervous system (ANS) is modulated by sleep and wakefulness.
      Noninvasive assessment of cardiac ANS with heart rate variability (HRV) analysis
      is a window for monitoring malfunctioning of cardiovascular autonomic modulation
      due to sleep deprivation. This study represents the first investigation of
      dynamic ANS effects and of electrophysiological and subjective sleepiness, in
      parallel, during 40 h of prolonged wakefulness under constant routine (CR)
      conditions. In eleven young male healthy subjects, ECG, EEG, EOG, and EMG chin
      recordings were performed during baseline sleep, during 40 h of sleep
      deprivation, and during recovery sleep. After sleep deprivation, slow-wave sleep
      and sleep efficiency increased, whereas HRV - global variability and HRV
      sympathovagal balance - was reduced (all p<0.05). Sleep-stage-dependent analysis
      revealed reductions in the sympathovagal balance only for NREM sleep stages (all
      p<0.05). Comparison of the daytime pattern of CR day one (CR baseline) with that
      of CR day two (CR sleep deprivation) disclosed an increase in subjective
      sleepiness, in the amount of unintended sleep, and in HRV sympathovagal balance,
      with accompaniment by increased EEG alpha attenuation (all p<0.05). Circadian
      rhythm analysis revealed the strongest influence on heart rate, with less
      influence on HRV sympathovagal balance. Hour-by-hour analysis disclosed the
      difference between CR sleep deprivation and CR baseline for subjective sleepiness
      at almost every single hour and for unintended sleep particularly in the morning
      and afternoon (both p<0.05). These findings indicate that 40 h of prolonged
      wakefulness lead in the following night to sleep-stage-dependent reduction in
      cardiac autonomic modulation. During daytime, an increased occurrence of
      behavioral and physiological signs of sleepiness was accompanied by diminished
      cardiac autonomic modulation. The observed changes are an indicator of autonomic
      stress due to sleep deprivation - which, if chronic, could potentially increase
      cardiovascular risk.

PMID- 24291387
TI  - Relationships between tongue motility, grip force, and survival in SOD1-G93A
      rats.
AB  - Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on
      spinal symptoms, despite the importance of bulbar deficits in progression of the
      disease. We sought to determine how bulbar deficits are related to spinal
      deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and
      hindlimb grip force and tongue motility in SOD1-G93A rats using statistical
      cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and
      tongue motility were used to cluster affected rats into groups. The analysis
      clustered one group that exhibited primarily forelimb deficits (forelimb group)
      and a second group that exhibited forelimb and tongue motility deficits
      (forelimb+bulbar group). The analysis did not identify a distinct hindlimb
      phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip
      force. Rats in the forelimb+bulbar group exhibited earlier and greater forelimb
      deficits, and earlier mortality than rats without bulbar deficits. Hindlimb
      deficits were similar in both groups. There was a significant correlation between
      forelimb grip force and tongue motility deficits, but not between forelimb and
      hindlimb deficits. These data extend clinical findings of a more rapid disease
      progression in individuals with bulbar symptoms to the SOD1-G93A rat model of
      ALS. 

PMID- 24291388
TI  - Intravenous infusion of gastrin-releasing peptide-27 and bombesin in rats reveals
      differential effects on meal size and intermeal interval length.
AB  - We have previously shown that the intraperitoneal (i.p.) administration of
      gastrin-releasing peptide-27 (GRP-27) or bombesin (BN) (at 0.21, 0.41 and
      1.03nmol/kg) reduces meal size (MS) and prolongs the intermeal interval (IMI).
      Here, we hypothesized that the intravenous (i.v.) administration of the same
      doses of GRP-27 and BN will be as effective as the i.p. administration in evoking
      these feeding responses. To test this hypothesis, we administered GRP-27 and BN
      i.v. and measured first MS (10% sucrose), IMI, satiety ratio (SR, IMI/MS) and
      second MS in overnight food-deprived but not water-deprived male Sprague Dawley
      rats. We found that (1) only GRP-27 reduced the first MS, (2) BN prolonged the
      IMI, (3) GRP-27 and BN increased the SR and (4) only BN reduced the size of the
      second meal. Contrary to our hypothesis, the i.v. administration of GRP-27 and BN
      affected the MS and IMI differently than did the i.p. administration. In
      conclusion, this pharmacological study suggests that the MS and IMI are regulated
      at different sites. 

PMID- 24291389
TI  - Mitochondrial uncoupling protein 2 protects splenocytes from oxidative stress
      induced apoptosis during pathogen activation.
AB  - Accumulating evidences suggested that mitochondrial uncoupling protein 2 (UCP2)
      is involved in host defense in parasite infection, inflammation, and autoimmune
      responses. However, it remains unknown whether UCP2 is participated in the
      modulation of humoral immune response. Here we used quantitative PCR, ELISA,
      TUNEL assay, flow cytometry, etc. to study the role of UCP2 in spleen B
      lymphocytes during pathogen activation and obtained following results. First,
      UCP2 is highly expressed in splenocytes and its expression level in splenocytes
      is rapidly increased when the cells are activated by lipopolysaccharide (LPS) in
      vivo or by LPS plus cytokines in vitro. Second, in contrast to the wild type (WT)
      littermates, the UCP2 knockout (UCP2-KO) mice show an impaired humoral immune
      response when they are challenged by pathogen. Although UCP2-KO mice produce a
      normal level of IgM, the levels of IgGs are significantly less than those of WT
      littermates. Third, splenocytes from UCP2-KO mice are more susceptible to
      pathogen activation-induced apoptosis, and the high level of reactive oxygen
      species (ROS) in UCP2-KO mice may be the cause for the apoptosis. In conclusion,
      our study demonstrates that mitochondrial UCP2 plays a critical role in
      protecting splenocytes from oxidative stress-induced apoptosis during pathogen
      activation. 

PMID- 24291390
TI  - Polymorphisms of endothelin 1 (G5665T and T-1370G) and endothelin receptor type A
      (C+70G and G-231A) in Graves' disease.
AB  - PURPOSE: Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing
      a key role in hypervascularization, thyroid follicle cell hyperplasia, and
      lymphocyte infiltration in the thyroid gland of patients with Graves' disease
      (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A
      (EDNRA). This study examined the possible association of EDN1 (G5665T and T
      1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with
      the occurrence of GD, and evaluates the relationship between genotypes and
      clinical/laboratory manifestations of GD. MATERIALS AND METHODS: We analyzed
      genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients
      with GD and 181 healthy controls by real-time PCR combined with melting curve
      analysis. RESULTS: No significant associations between GD and variant alleles of
      the studied polymorphisms were observed. However, the anti-thyroid peroxidase
      (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype
      were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026,
      respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous
      patients were found to be higher than in mutant gene carrying patients (GT+GG)
      (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold
      increased risk for development of ophthalmopathy in GD patients (p=0.009).
      CONCLUSION: Although there were no associations between EDN1 (G5665T and T-1370G)
      and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T
      1370G polymorphisms were related to alterations of autoantibody production and
      EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD
      patients.

PMID- 24291391
TI  - Downregulation of NO and PGE2 in LPS-stimulated BV2 microglial cells by trans
      isoferulic acid via suppression of PI3K/Akt-dependent NF-kappaB and activation of
      Nrf2-mediated HO-1.
AB  - Little is known about whether trans-isoferulic acid (TIA) regulates the
      production of lipopolysaccharide (LPS)-induced proinflammatory mediators.
      Therefore, we examined the effect of TIA isolated from Clematis mandshurica on
      LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2
      microglial cells. We found that TIA inhibited the production of LPS-induced NO
      and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also
      downregulated the expression levels of specific regulatory genes such as
      inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS
      induced NF-kappaB activity via dephosphorylation of PI3K/Akt. In addition, we
      demonstrated that a specific NF-kappaB inhibitor PDTC and a selective PI3K/Akt
      inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS
      and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-kappaB activity,
      suggesting that TIA attenuates the expression of these proinflammatory genes by
      suppressing PI3K/Akt-mediated NF-kappaB activity. Our results showed that TIA
      suppressed NO and PGE2 production through the induction of nuclear factor
      erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken
      together, our data indicate that TIA suppresses the production of proinflammatory
      mediators such as NO and PGE2, as well as their regulatory genes, in LPS
      stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-kappaB
      activity and enhancing Nrf2-mediated HO-1 expression. 

PMID- 24291392
TI  - Bile enhances glucose uptake, reduces permeability, and modulates effects of
      lectins, trypsin inhibitors and saponins on intestinal tissue.
AB  - Antinutritional factors (ANFs) can disrupt digestive and other intestinal
      functions. ANFs in soybean meal (SBM) are implicated in proliferative and
      inflammatory responses in the intestine of various (functionally) monogastric
      animals, including Atlantic salmon (Salmo salar L.). The goal of the current
      study was to investigate the effect of ex vivo exposure of mid and distal
      intestinal tissue of salmon to soybean saponins (SAP), lectin (LEC) and Kunitz'
      trypsin inhibitor (KTI), singly and in combination, on epithelial function, as
      assessed by measuring in vitro glucose uptake pathways along a glucose
      concentration gradient. As solubilization of SAP in the calcium-containing
      Ringer's solution was problematic but resolved with the addition of a
      physiological concentration of bile collected from the gall bladder of salmon, an
      evaluation of bile effects became an added element. Results indicated that bile
      increased baseline glucose absorption and possibly transport, and also had a
      protective effect on the epithelial barrier, at least partially due to
      taurocholate. Compared to controls, tissues exposed to LEC+bile, KTI+bile and
      LEC+KTI+bile exhibited increased glucose uptake at the higher glucose
      concentrations, apparently due to markedly increased tissue permeability.
      Addition of SAP, however, attenuated the response, possibly by binding bile
      components. SAP+bile, also in combination with LEC and/or KTI, as well as LEC,
      KTI and LEC+KTI without bile often reduced transcellular glucose uptake pathways,
      while maintaining low tissue permeability. SAP+LEC+KTI+bile, LEC and KTI caused
      the most marked reductions. The distal intestine was more affected, reflecting
      the restriction of in vivo SBM-induced inflammatory changes to this region. 

PMID- 24291393
TI  - Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti
      inflammatory potential of apigenin.
AB  - Apigenin has gained particular interests in recent years as a beneficial and
      health promoting agent because of its low intrinsic toxicity. Vitexin and
      isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been
      known to possess potent anti-diabetic, anti-Alzheimer's disease (anti-AD), and
      anti-inflammatory activities. The present study was designed to investigate the
      anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C
      glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat
      lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced
      glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B),
      acetylcholinesterase (AChE), butyrylcholinesterase (BChE), beta-site amyloid
      precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide
      (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most
      potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the
      most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic
      and anti-AD potentials, apigenin showed powerful antiinflammatory activity by
      inhibiting NO production and iNOS and COX-2 expression while vitexin and
      isovitexin were inactive. Therefore, it could be speculated that C-glycosylation
      of apigenin at different positions might be closely linked to relative intensity
      of anti-diabetic, anti-AD, and anti-inflammatory potentials. 

PMID- 24291394
TI  - A chemical approach for the reduction of beauvericin in a solution model and in
      food systems.
AB  - Beauvericin (BEA) is a bioactive compound produced by the secondary metabolism of
      several Fusarium strains with a strong antibacterial, antifungal, and
      insecticidal activities. This study evaluated the reduction of BEA added at 25
      mg/kg in phosphate buffer saline (PBS) solutions at pH of 4, 7 and 10, or to
      different cereal products (kernels and flours) by the bioactive compounds phenyl
      isothiocyanate (PITC) and benzyl isothiocyanate (BITC). The concentration of the
      mycotoxin was evaluated using liquid chromatography coupled to the diode array
      detector (LC-DAD). In solution, BEA reduction ranged from 9% to 94% on a time
      dependent fashion and lower pH levels resulted in higher BEA reduction. Cereal
      kernels and flours treated with gaseous PITC and BITC (50, 100 and 500 MUL/L)
      presented BEA reduction from 9% to 97% and was dose-dependent. Among the crops,
      corn was the vehicle where BEA was mostly affected by the action of the ITCs,
      followed by wheat and rice, and lastly barley. Overall, PITC caused higher
      reduction of BEA and should be chosen over BITC as a fumigant to decrease the
      levels of this mycotoxin in grains and flours.

PMID- 24291395
TI  - Attentional bias and attentional control in Posttraumatic Stress Disorder.
AB  - Extensive evidence exists for an association between attentional bias (AB;
      attentional vigilance or avoidance) and anxiety. Recent studies in healthy
      participants suggest that attentional control (AC) may facilitate inhibition of
      automatic attentional processes associated with anxiety. To investigate
      relationships among AC, trauma-related AB, symptom severity and trait anxiety in
      patients with Posttraumatic Stress Disorder (PTSD), participants (N = 91)
      completed self-report measures of AC, posttraumatic stress symptoms (PTSS) and
      trait anxiety. AB was measured with a pictorial version of the Dot Probe Test. AC
      moderated the relationship between PTSS and AB (threat avoidance). Patients high
      in PTSS and low in AC showed attentional avoidance. No association between PTSS
      and AB in patients with medium or high levels of AC was found. A similar pattern
      of results was observed for the relationship between trait anxiety, AC and AB.
      These results suggest that a low ability to control attention is a risk factor
      for AB in PTSD. This first clinical study corroborates the accumulating evidence
      from analog studies that individual differences in top-down attentional control
      are of considerable importance in the expression of AB in anxious
      psychopathology.

PMID- 24291396
TI  - Nail picking disorder (onychotillomania): a case report.
AB  - Nail picking disorder (onychotillomania) is characterized by excessive picking or
      pulling at one's own finger- or toenails. This condition has received scant
      research attention and may be related to other body focused repetitive behaviors
      such as pathological nail biting, skin picking and hair pulling. We present a
      case of a male client with a chronic and severe nail picking habit treated with
      acceptance-enhanced behavior therapy. The client showed clinical characteristics
      similar to other body focused repetitive behaviors and responded moderately well
      to the treatment. 

PMID- 24291397
TI  - A meta-analytic clarification of the relationship between posttraumatic growth
      and symptoms of posttraumatic distress disorder.
AB  - Traumatic experiences can have a powerful impact on individuals and communities
      but the relationship between perceptions of beneficial and pathological outcomes
      are not known. Therefore, this meta-analysis examined both the strength and the
      linearity of the relationship between symptoms of posttraumatic stress disorder
      (PTSD) and perceptions of posttraumatic growth (PTG) as well as identifying the
      potential moderating roles of trauma type and age. Literature searches of all
      languages were conducted using the ProQuest, Wiley Interscience, ScienceDirect,
      Informaworld and Web of Science databases. Linear and quadratic (curvilinear) rs
      as well as betas were analysed. Forty-two studies (N = 11,469) that examined both
      PTG and symptoms of PTSD were included in meta-analytic calculations. The
      combined studies yielded a significant linear relationship between PTG and PTSD
      symptoms (r = 0.315, CI = 0.299, 0.331), but also a significantly stronger (as
      tested by Fisher's transformation) curvilinear relationship (r =0.372, CI =
      0.353, 0.391). The strength and linearity of these relationships differed
      according to trauma type and age. The results remind those working with
      traumatised people that positive and negative post-trauma outcomes can co-occur.
      A focus only on PTSD symptoms may limit or slow recovery and mask the potential
      for growth.

PMID- 24291399
TI  - Peptides that activate the 20S proteasome by gate opening increased oxidized
      protein removal and reduced protein aggregation.
AB  - The proteasome is a multicatalytic protease that is responsible for the
      degradation of the majority of intracellular proteins. Its role is correlated
      with several major regulatory pathways that are involved in cell cycle control,
      signaling, and antigen presentation, as well as in the removal of oxidatively
      damaged proteins. Although several proteasomal catalytic inhibitors have been
      described, very few activators have been reported to date. Some reports in the
      literature highlight the cellular protective effects of proteasome activation
      against oxidative stress and its effect on increased life span. In this work, we
      describe a peptide named proteasome-activating peptide 1 (PAP1), which increases
      the chymotrypsin-like proteasomal catalytic activity and, consequently,
      proteolytic rates both in vitro and in culture. PAP1 proteasomal activation is
      mediated by the opening of the proteasomal catalytic chamber. We also demonstrate
      that the observed proteasomal activation protected cells from oxidative stress;
      further, PAP1 prevented protein aggregation in a cellular model of amyotrophic
      lateral sclerosis. The role of 20SPT gate opening underlying protection against
      oxidative stress was also explored in yeast cells. The present data indicate the
      importance of proteasomal activators as potential drugs for the treatment of
      pathologies associated with the impaired removal of damaged proteins, which is
      observed in many neurodegenerative diseases. 

PMID- 24291400
TI  - Retinoic acid differentially affects in vitro proliferation, differentiation and
      mineralization of two fish bone-derived cell lines: different gene expression of
      nuclear receptors and ECM proteins.
AB  - Retinoic acid (RA), the main active metabolite of vitamin A, regulates vertebrate
      morphogenesis through signaling pathways not yet fully understood. Such process
      involves the specific activation of retinoic acid and retinoid X receptors (RARs
      and RXRs), which are nuclear receptors of the steroid/thyroid hormone receptor
      superfamily. Teleost fish are suitable models to study vertebrate development,
      such as skeletogenesis. Cell systems capable of in vitro mineralization have been
      developed for several fish species and may provide new insights into the specific
      cellular and molecular events related to vitamin A activity in bone,
      complementary to in vivo studies. This work aims at investigating the in vitro
      effects of RA (0.5 and 12.5 MUM) on proliferation, differentiation and
      extracellular matrix (ECM) mineralization of two gilthead seabream bone-derived
      cell lines (VSa13 and VSa16), and at identifying molecular targets of its action
      through gene expression analysis. RA induced phenotypic changes and cellular
      proliferation was inhibited in both cell lines in a cell type-dependent manner
      (36-59% in VSa13 and 17-46% in VSa16 cells). While RA stimulated mineral
      deposition in VSa13 cell cultures (50-62% stimulation), it inhibited the
      mineralization of extracellular matrix in VSa16 cells (11-57% inhibition).
      Expression of hormone receptor genes (rars and rxrs), and extracellular matrix
      related genes such as matrix and bone Gla proteins (mgp and bglap), osteopontin
      (spp1) and type I collagen (col1a1) were differentially regulated upon exposure
      to RA in proliferating, differentiating and mineralizing cultures of VSa13 and
      VSa16 cells. Altogether, our results show: (i) RA affects proliferative and
      mineralogenic activities in two fish skeletal cell types and (ii) that during
      phenotype transitions, specific RA nuclear receptors and bone-related genes are
      differentially expressed in a cell type-dependent manner.

PMID- 24291398
TI  - KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun.
AB  - Loss-of-function mutations in the KRIT1 gene (CCM1) have been associated with the
      pathogenesis of cerebral cavernous malformations (CCM), a major cerebrovascular
      disease. However, KRIT1 functions and CCM pathogenetic mechanisms remain
      incompletely understood. Indeed, recent experiments in animal models have clearly
      demonstrated that the homozygous loss of KRIT1 is not sufficient to induce CCM
      lesions, suggesting that additional factors are necessary to cause CCM disease.
      Previously, we found that KRIT1 is involved in the maintenance of the
      intracellular reactive oxygen species (ROS) homeostasis to prevent ROS-induced
      cellular dysfunctions, including a reduced ability to maintain a quiescent state.
      Here, we show that KRIT1 loss of function leads to enhanced expression and
      phosphorylation of the redox-sensitive transcription factor c-Jun, as well as
      induction of its downstream target COX-2, in both cellular models and human CCM
      tissues. Furthermore, we demonstrate that c-Jun upregulation can be reversed by
      either KRIT1 re-expression or ROS scavenging, whereas KRIT1 overexpression
      prevents forced upregulation of c-Jun induced by oxidative stimuli. Taken
      together with the reported role of c-Jun in vascular dysfunctions triggered by
      oxidative stress, our findings shed new light on the molecular mechanisms
      underlying KRIT1 function and CCM pathogenesis. 

PMID- 24291401
TI  - Eldecalcitol replaces endogenous calcitriol but does not fully compensate for its
      action in vivo.
AB  - Calcitriol (1alpha,25-dihydroxyvitamin D3, 1alpha,25(OH)2D3) is an essential
      hormone that works in cooperation with parathyroid hormone (PTH) and fibroblast
      growth factor-23 (FGF-23) to regulate calcium and phosphorus homeostasis.
      Previous in vivo studies in rats have shown that eldecalcitol, a vitamin D
      analog, is more active than calcitriol in stimulating calcium and phosphorus
      absorption in the intestine and in increasing serum FGF-23, but is not as active
      in suppressing blood PTH. However, those results are problematic because
      administration of exogenous eldecalcitol or calcitriol affects the synthesis and
      degradation of endogenous calcitriol, and competes for binding to vitamin D
      receptor (VDR) in target tissues. Therefore, we tried to evaluate the 'true
      biological activity in vivo' of each compound by comparing their biological
      activities with respect to their blood concentrations. In VDR gene knockout mice,
      calcitriol and eldecalcitol did not affect either serum or urinary calcium
      levels, and also did not induce the expression of target genes. These results
      indicate that the actions of eldecalcitol are mediated by VDR. In normal rats,
      concentrations of both calcitriol and eldecalcitol in the blood increased dose
      dependently and had a linear correlation with administered dosage. The
      concentration of calcitriol in the blood was reduced by eldecalcitol treatment,
      falling to below the limit of detection at 0.1MUg/kg eldecalcitol. Based on the
      concentration of each compound in the blood, eldecalcitol had approximately 1/4
      to 1/7 the activity of calcitriol to increase serum calcium, FGF-23, and urinary
      calcium excretion, and to suppress blood PTH. Eldecalcitol dose-dependently
      increased urinary phosphorus excretion and reduced serum phosphorus. However,
      calcitriol did not change serum phosphorus. In accordance with serum chemistry
      and hormones, a concentration of eldecalcitol in the blood of 3-8 times that of
      calcitriol was required to stimulate target gene expressions in the kidneys (VDR,
      TRPV5, and calbindin-D28k) and bone (VDR, FGF-23, and RANKL). On the other hand,
      the blood concentrations of eldecalcitol needed to stimulate target genes in the
      intestine (TRPV6, calbindin-D9k, and VDR) were comparable to those of calcitriol.
      These results indicate that oral administration of eldecalcitol stimulates target
      gene expression in the intestine similarly to calcitriol, but to a much lesser
      extent than calcitriol in the kidneys and bones. The major finding of the present
      study is that eldecalcitol suppresses endogenous calcitriol and replaces it.
      However, it may not fully compensate for the action of calcitriol in vivo. This
      article is part of a Special Issue entitled '16th Vitamin D Workshop'. 

PMID- 24291402
TI  - Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women:
      is it safe?
AB  - Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and
      was generally considered to be safe until the results of long-term studies of
      postmenopausal hormone therapy (HT) using treatment with conjugated equine
      estrogens (CEE) combined with MPA and CEE alone suggested that MPA, and perhaps
      other progestogens, may play a role in the increased risk of breast cancer and
      cardiovascular diseases. This review examines critically the safety of MPA in
      terms of breast cancer and cardiovascular disease risk, and its effects on brain
      function. Research into mechanisms by which MPA might cause adverse effects in
      these areas, combined with the available clinical evidence, suggests a small
      increase in relative risk for breast cancer and stroke, and a decline in
      cognitive function, in older women using MPA with an estrogen for postmenopausal
      HT. However, short-term (less than 5 years) use of MPA with an estrogen in the
      years immediately after the onset of menopause for the management of vasomotor
      symptoms does not appear to be associated with any increased risk of these
      disorders. 

PMID- 24291403
TI  - Pathology of Yersinia entomophaga MH96 towards Costelytra zealandica (Coleoptera;
      Scarabaeidae) larvae.
AB  - The bacterium Yersinia entomophaga was isolated from larvae of the New Zealand
      grass grub, Costelytra zealandica (Coleoptera: Scarabaeidae), found in soil.
      Following ingestion of a lethal dose of bacteria, larvae of C. zealandica reduced
      feeding activity and movement. After approximately 4h infected larvae convulsed
      and regurgitated dark digestive fluid and expelled frass pellets leaving the
      midgut empty and the larva amber in appearance. In the initial stages of
      infection, ingested bacteria were mostly contained within the peritrophic
      membrane and expelled with the gut fluid or transferred into the hind gut. While
      few Y. entomophaga were associated with the midgut epithelial cells, by 24h cells
      were swelling and bursting with vesicles being expelled into the midgut lumen. By
      48h, bacteria had entered the haemocoel and the midgut cells had further
      deteriorated. After 72h, the cellular remnants were totally detached from the
      basal membrane the infected insects were filled with bacteria and moribund or
      dead with septicaemia. Mortality was directly proportional to dose and time after
      infection. By applying a range of doses, the LD50 was determined as 2.9*10(4)Y.
      entomophaga per C. zealandica larva, with an LT50 of 2.94days for doses
      of>1*10(5) per larva. Ingestion of low doses of bacteria did not inhibit feeding
      activity but led more slowly to death. By time of death, Y. entomophaga had
      multiplied, approximately 500 fold, in the cadavers of the infected larvae. 

PMID- 24291404
TI  - Quinine sensitivity influences the acceptance of sea-buckthorn and grapefruit
      juices in 9- to 11-year-old children.
AB  - The acceptance of novel foods by children is related to a number of factors, and
      differences in taste sensitivity may form some specific challenges. High
      sensitivity might be a barrier to the acceptance of sour/bitter products by
      children. This study investigated the effect of sensitivity to bitter, sour,
      sweet, and salty tastes on the acceptance of Nordic juices in 9- to 11-year-old
      children. A total of 328 children were subjected to two taste sensitivity tests
      for quinine, citric acid, sucrose, and NaCl. Their acceptance of six juices
      (carrot, rosehip, sea-buckthorn, lingonberry, grapefruit, and aronia) was
      measured. Bitter sensitivity was found to be significantly correlated to the
      intake of the sweet sea-buckthorn and lingonberry juices; the most bitter
      sensitive children exhibited the highest intake of these juices. The opposite
      relationship was found for bitter sensitivity and the intake of the bitter
      grapefruit juice. Sour, sweet, and salt sensitivities did not affect the intake
      of any of the juices. Liking scores were not affected by sensitivity. In
      conclusion, bitter sensitivity appears to influence food intake in children to a
      greater extent than sour, sweet, or salt sensitivity. Bitter-sensitive children
      exhibited a reduced intake of grapefruit juice and a higher intake of sucrose
      sweetened juices. Thus, bitter sensitivity might be a challenge in the acceptance
      of certain bitter foods. 

PMID- 24291405
TI  - The crunch factor's role in golf-related low back pain.
AB  - BACKGROUND CONTEXT: The golf swing exposes the spine to complex torsional,
      compressive, and shearing loads that increase a player's risk of injury. The
      crunch factor (CF) has been described as a measure to evaluate the risk of low
      back injuries in golfers and is based on the notion that lateral flexion and
      axial trunk rotation jointly contribute to spinal degeneration. However, few
      studies have evaluated the appropriateness of this measure in golfers with low
      back pain (LBP). PURPOSE: To objectively examine the usefulness of the CF as a
      measure for assessing the risk of low back injury in golfers. STUDY DESIGN: Field
      based research using a cross-sectional design. METHODS: This research used three
      dimensional motion analysis to assess the golf swings of 12 golfers with LBP and
      15 asymptomatic controls. Three-dimensional kinematics were derived using Vicon
      Motus, and the CF was calculated as the instantaneous product of axial trunk
      rotation velocity and lateral trunk flexion angle. RESULTS: Maximum CFs and their
      timings were not significantly different between the symptomatic and asymptomatic
      groups. Furthermore, for those golfers who produced higher CFs (irrespective of
      the group), the increased magnitude could not be attributed to an increased axial
      angular trunk velocity or lateral flexion angle, but rather to a concomitant
      increase in both of these variables. CONCLUSIONS: The findings suggested that
      although the fundamental concepts that underpin the CF seem sensible, this
      measure does not appear to be sensitive enough to distinguish golfers with LBP
      from the asymptomatic players.

PMID- 24291406
TI  - Modulation of annulus fibrosus cell alignment and function on oriented
      nanofibrous polyurethane scaffolds under tension.
AB  - BACKGROUND CONTEXT: Annulus fibrosus (AF), a component of the intervertebral disc
      (IVD), is always under tension in vivo, a condition that must be taken into
      consideration when tissue engineering an IVD. Loss of the tensile forces has been
      implicated in the pathogenesis of disc degeneration characterized by mechanical
      and structural breakdown of the AF. PURPOSE: In this study, we hypothesize that
      tensile forces modulate cellular and molecular behavior of AF cells grown on
      nanofibrous scaffolds in vitro. STUDY DESIGN/SETTING: Bovine AF cells were seeded
      onto strained electrospun-aligned nanofibrous polycarbonate urethane (PU)
      scaffolds. Tension was either maintained throughout the culture duration
      (monotonic) or removed after 24 hours (relaxed). METHODS: The effect of tension
      on AF cells cultured on PU scaffolds was evaluated over 7 days by scanning
      electron microscopy, biochemical assays, immunofluorescence microscopy, and
      quantitative polymerase chain reaction. RESULTS: Cells grown on the relaxed
      scaffold were significantly more proliferative, synthesized more collagen and had
      increased collagen type I and TGFbeta-1 gene expression; however these cells were
      not as aligned as were the cells and matrix on monotonic strained scaffolds. The
      alignment of AF cells grown on monotonic scaffolds correlated with significantly
      greater scaffold elastic modulus on day 7. Additionally, the cellular response to
      the change in strain was delayed by 3 to 5 days after tension release, which
      correlated with the time at which changes in scaffold length were detected.
      CONCLUSIONS: This study demonstrated that AF cells respond at the molecular and
      cellular level to the changes in matrix/scaffold tension. This suggests that it
      may be necessary to determine the optimal elastic modulus and applied tensile
      forces to tissue engineer an AF that mimics the native tissue. Furthermore, this
      study provides insight into how changes in tensile forces may lead to changes in
      the AF cell function.

PMID- 24291407
TI  - Similar outcome despite slight clinical differences between lumbar radiculopathy
      induced by lateral versus medial disc herniations in patients without previous
      foraminal stenosis: a prospective cohort study with 1-year follow-up.
AB  - BACKGROUND CONTEXT: It has been claimed that lumbar radiculopathy induced by
      foraminal disc herniations had poorer outcome and different clinical features,
      including: 1-more progressive onset, but shorter duration between the first sign
      and request of medical care; 2-more severe radiculopathy; 3-less frequent/severe
      back pain; 4-less limitation of straight leg raising (SLR); 5-more frequent
      neurologic deficiencies; 6-poorer outcome. PURPOSE: To check whether this still
      holds true when including only patients without other reasons for foraminal
      stenosis, that is, whether patients with medial disc herniations had different
      features and outcome than those with more lateral disc herniations. STUDY DESIGN:
      All patients hospitalized to treat a lumbar radiculopathy within a 6-month period
      in two French rheumatology units in 2012 were included in this prospective study
      each time computed tomography scan or magnetic resonance imaging had already been
      performed and showed clear disc bulging/herniation but no features of medial or
      lateral spinal stenosis. PATIENT SAMPLE: Fifty-nine patients (31 males, 49 with
      sciatica only) were included: 31 (53%) had medial disc herniations and 28 (47%)
      had more lateral herniations (posterolateral in 3, foraminal in 20, and far
      lateral in 5). OUTCOME MEASURES: Outcome was assessed by a phone call 1 year
      after the baseline assessment using a standardized questionnaire. Patients were
      asked whether they experienced a relapse of their radiculopathy after discharge
      from the hospital; whether they had been operated or not; whether they felt it
      had improved or not; whether they felt cured or not; to assess their level of
      pain radiating in the leg when standing on a 0 to 10 verbal scale; and how long
      they could walk. METHODS: Features of patients with medial disc herniations were
      compared with patients with more lateral herniations. RESULTS: No significant
      differences according to the location of herniations were noticed for the speed
      of radiculopathy onset, time elapsed since onset, back pain (both lying or
      standing), and leg pain (both lying or standing), but slight significant
      differences (t test<0.05) were observed for other items: the 28 patients with
      lateral herniations were 8 years older (53.4 +/-15.8 vs. 45.2+/-12.6), their
      herniations involved discs from upper levels of the lumbar spine (above L4-L5:
      7/28 vs. 3/31), motor weakness was more frequent (25% vs. 3%), SLR was less
      restricted (65.0 degrees +/-24.5 degrees  vs. 51.1 degrees +/-25.7 degrees ), DN4
      score of neuropathic pain was higher (4.4+/-2.1 vs. 3.2+/-1.8), anxiety level was
      higher (10.3+/-4.1 vs. 7.9+/-3.2), length of hospital stay was longer (5.7+/-2.4
      days vs. 4.5+/-1.4 days), and physician's prognosis of a good outcome was poorer
      (6.6+/-2.2 vs. 8.0+/-1.6). However, at the end of follow-up (12.2+/-3.3 months),
      outcome was similar: 37% (vs. 41% for medial herniations) had transiently
      relapsed, 66% felt finally improved (vs. 63%), and walking capacity was nearly
      identical despite the fact that only 18% had to be operated (vs. 32% of those
      with medial herniations). CONCLUSIONS: Despite differences in clinical
      presentation, the outcome of radiculopathy induced by the more lateral lumbar
      disc herniations was not worse than the outcome of patients with only medial disc
      herniations. Previous claims of poorer outcome in foraminal herniations might be
      explained by the inclusion of patients with associated foraminal stenosis.

PMID- 24291408
TI  - Brace treatment of thoracolumbar kyphosis in spondylometaphyseal dysplasia with
      restoration of vertebral morphology and sagittal profile: a case report.
AB  - BACKGROUND CONTEXT: The Kozlowski type of spondylometaphyseal dysplasia (SMD-K)
      is characterized by vertebral and metaphyseal abnormalities. The longitudinal
      evolution of thoracolumbar kyphosis associated with vertebral anomalies in SMD-K
      is unclear. PURPOSE: To document the longitudinal changes in sagittal alignment
      and vertebral morphology in a patient with SMD-K treated nonoperatively with a
      Milwaukee brace. STUDY DESIGN/SETTING: Case report. PATIENT SAMPLE: Patient with
      SMD-K having multiple vertebral anomalies and a thoracolumbar kyphosis. METHODS:
      A girl with SMD-K seen initially at 21 months old was followed for 14 years. She
      presented with thoracolumbar kyphosis associated with multiple vertebral
      anomalies consisting primarily of hypoplasia at L1, beaking at L2, and ovoid
      shape of adjacent vertebrae. The patient was treated with a Milwaukee brace and
      followed until she was 16 years old. RESULTS: After initiation of brace
      treatment, the thoracolumbar kyphosis gradually resolved and she had a normal
      sagittal alignment at last follow-up. Normal vertebral morphology was also
      completely restored in the sagittal plane. The patient developed a main thoracic
      scoliosis that did not require additional treatment. CONCLUSIONS: Nonoperative
      treatment with bracing can be attempted in patients with SMD-K affected by
      thoracolumbar kyphosis and multiple vertebral anomalies, because full restoration
      of normal sagittal alignment and vertebral morphology is possible.

PMID- 24291409
TI  - Interspinous device versus laminectomy for lumbar spinal stenosis: a comparative
      effectiveness study.
AB  - BACKGROUND CONTEXT: Currently no studies directly compare effectiveness between
      interspinous devices (IDs) and laminectomy in lumbar spinal stenosis (LSS)
      patients. PURPOSE: To compare reoperations, complications, and costs between LSS
      patients undergoing ID placement versus laminectomy. STUDY DESIGN: Retrospective
      comparative study. PATIENT SAMPLE: The MarketScan database (2007-2009) was
      queried for adults with LSS undergoing ID placement as a primary inpatient
      procedure. OUTCOME MEASURES: Reoperation rates, complication rates, and costs.
      METHODS: Each ID patient was matched with a laminectomy patient using propensity
      score matching. Reoperations, complications, and costs were analyzed in patients
      with at least 18 months postoperative follow-up. The authors did not receive
      funding from any external sources for this study. RESULTS: Among 498 inpatients
      that underwent ID placement between 2007 and 2009; the average age was 73 years.
      The cumulative reoperation rates after ID at 12 and 18 months were 21% and 23%,
      respectively. The average inpatient hospitalization lasted 1.6 days with an
      associated cost of $17,432. Two propensity-matched cohorts of 174 patients that
      had undergone ID versus laminectomy were analyzed. Longer length of stay was
      observed in the laminectomy cohort (2.5 days vs. 1.6 days, p<.0001), whereas ID
      patients accrued higher costs at index hospitalization ($17,674 vs. $12,670,
      p=.0001). Index hospitalization (7.5% vs. 3.5%, p=.099) and 90-day (9.2% vs.
      3.5%, p=.028) complications were higher in the laminectomy cohort compared with
      the ID cohort. The ID patients had significantly higher reoperation rates than
      laminectomy patients at 12 months follow-up (12.6% vs. 5.8%, p=.026) and incurred
      higher cumulative costs than laminectomy patients at 12 months follow-up ($39,173
      vs. $34,324, p=.289). CONCLUSIONS: Twelve-month reoperation rates and index
      hospitalization costs were significantly higher among patients who underwent ID
      compared with laminectomy for LSS.

PMID- 24291410
TI  - Risk factors for nonorganic low back pain in patients with worker's compensation.
AB  - BACKGROUND CONTEXT: Nonorganic low back pain (NOLBP) is common in the worker's
      compensation (WC) population. Consults with specialists constitute an unnecessary
      cost to the system, and a means of screening for these patients is necessary.
      PURPOSE: To design easily identifiable criteria to help identify which WC
      patients are likely to have nonorganic pain. STUDY DESIGN: A retrospective chart
      review of WC patients with low back pain (LBP) seen in consultation by a single
      spine surgeon over a 2-year period at a university medical center. PATIENT
      SAMPLE: One hundred twenty-seven WC patients with LBP were seen in consultation
      by a single spine surgeon over a 2-year period. All were referred for surgical
      evaluation. Potential risk factors for nonorganic pain were identified, which
      included alleged injury in multiple bodily areas, presence of concomitant
      cervical and/or thoracic complaints, initial presentation to chiropractor,
      mechanism of injury including slip and fall or lifting of a patient, number of
      previous independent medical examinations performed, presence of psychiatric
      diagnosis, areas of pain different from first report of injury, greater than 13
      months between evaluations, occupation as a health-care employee, presence of
      legal representation, amount of time off work, present work status (working or
      disabled), and number of previous WC claims. OUTCOME MEASURES: Outcome measures
      included the number of Waddell's signs and additional nonorganic/inconsistent
      pain behaviors noted during the examination by the spine specialist. Nonorganic
      low back pain was defined as four or more Waddell's signs or three Waddell's
      signs plus one additional inconsistent behavior. METHODS: A stepwise logistic
      regression was used to determine which of the risk factors were significantly
      associated with nonorganic pain, correcting for age and sex. We then used an
      analysis of deviance to determine which combination of factors could best
      differentiate patients with nonorganic findings. RESULTS: Factors that were
      significantly associated with nonorganic pain included mechanism of injury
      including slip and fall or lifting of a patient (odds ratio [OR]=5.7, p=.03),
      alleged injury in greater than two bodily areas (OR=4.2, p=.02), presence of
      concomitant cervical and thoracic complaints (OR=2.9, p=.04), initial
      presentation to chiropractor (OR=7.7, p=.01), and back pain not listed on first
      report of injury (OR=3.3, p=.04). Patients with three or more of these findings
      were found to be at a very high risk of having nonorganic pain (greater than
      95%). CONCLUSIONS: We found a significant association between certain easily
      identifiable criteria and NOLBP in a cohort of WC patients. These criteria
      included mechanism of injury including slip and fall or lifting of a patient,
      alleged injury in greater than two bodily areas, presence of concomitant cervical
      and/or thoracic complaints, initial presentation to chiropractor, and areas of
      pain different from first report of injury. More than 95% of patients with three
      or more of the aforementioned criteria were found to have nonorganic pain. This
      information may help the specialist and the WC provider identify patients at a
      high risk for nonorganic pain, thereby reducing unnecessary costs.

PMID- 24291411
TI  - Multipoint left ventricular pacing improves acute hemodynamic response assessed
      with pressure-volume loops in cardiac resynchronization therapy patients.
AB  - BACKGROUND: Conventional cardiac resynchronization therapy (CRT) improves acute
      cardiac hemodynamics. OBJECTIVE: To investigate if CRT with multipoint left
      ventricular (LV) pacing in a single coronary sinus branch (MultiPoint Pacing
      [MPP], St Jude Medical, Sylmar, CA) can offer further hemodynamic benefits to
      patients. METHODS: Forty-four consecutive patients (80% men, New York Heart
      Association III, end-systolic volume 180 +/- 77 mL, ejection fraction 27% +/- 6%,
      and QRS duration 152 +/- 17 ms) receiving a CRT device implant (Unify Quadra MP
      or Quadra Assura MP and Quartet LV lead, St Jude Medical) underwent
      intraoperative assessment of LV hemodynamics by using a pressure-volume loop
      system (Inca, CD Leycom). A pacing protocol was performed, including 9
      biventricular pacing interventions with conventional CRT (CONV) using distal and
      proximal LV electrodes and various MPP configurations. Each pacing intervention
      was performed twice in randomized order with right ventricular pacing (BASELINE)
      repeated after every intervention. RESULTS: Evaluable recordings were obtained in
      42 patients. Relative to BASELINE, the best MPP intervention significantly
      increased the rate of pressure change (dP/dtmax; 15.9% +/- 10.0% vs 13.5% +/-
      8.8%; P < .001), stroke work (27.2% +/- 42.5% vs 19.4% +/- 32.2%; P = .018),
      stroke volume (10.4% +/- 22.5% vs 4.1% +/- 13.1%; P = .003), and ejection
      fraction (10.5% +/- 20.9% vs 5.3% +/- 13.2%; P = .003) as compared with the best
      CONV intervention. Moreover, the best MPP intervention improved acute diastolic
      function, significantly decreasing -dP/dtmin (-13.5% +/- 10.2% vs -10.6% +/-
      6.8%; P = .011), relaxation time constant (-7.5% +/- 9.0% vs -4.8% +/- 7.2%; P =
      .012), and end-diastolic pressure (-18.2% +/- 22.4% vs -8.7% +/- 21.4%; P < .001)
      as compared with the best CONV intervention. CONCLUSIONS: CRT with MPP can
      significantly improve acute LV hemodynamic parameters assessed with pressure
      volume loop measurements as compared with CONV.

PMID- 24291412
TI  - Durability of the survival effect of cardiac resynchronization therapy by level
      of left ventricular functional improvement: fate of "nonresponders".
AB  - BACKGROUND: Although improvement in left ventricular (LV) function has been shown
      to portend superior short-term outcomes in patients with heart failure undergoing
      cardiac resynchronization therapy (CRT), the durability of this effect at 5 years
      has not been established. OBJECTIVE: To determine the long-term outcomes of
      patients undergoing CRT on the basis of the degree of echocardiographic response.
      METHODS: We extracted clinical data on a cohort of 880 consecutive patients
      undergoing the new implantation of a CRT device between September 30, 2003, and
      August 6, 2007. Patients with an ejection fraction (EF) <=35% undergoing initial
      CRT implantation, with an available pre-CRT and follow-up echocardiogram, were
      included in the final cohort. On the basis of changes in LVEF, patients were
      categorized into "nonresponders" (change in EF <=4%), "responders" (EF change 5%
      20%), and "super-responders" (change in EF >20%). A Cox multivariate model was
      performed to determine the effect of response on long-term survival free of LV
      assist device or heart transplant. RESULTS: A total of 526 patients met inclusion
      criteria, of whom 196 (37.3%) were classified as nonresponders, 236 (44.9%) as
      "responders," and 94 (17.9%) as "super-responders." In multivariate analysis,
      "super-responders" had the best survival and nonresponders the worst over a mean
      of follow-up of 5.3 +/- 2.4 years. At 5 years, survival free of LV assist device
      or heart transplant among super-responders was 82%; responders, 70%; and
      nonresponders, 48%. CONCLUSIONS: In patients with heart failure undergoing CRT,
      survival benefit is durable at 5 years of follow-up and its degree intimately
      tied to the level of improvement in ventricular function. The prognosis of
      nonresponders is exceptionally poor.

PMID- 24291414
TI  - Incidence, management, and outcomes of the arteriovenous fistula complicating
      transvenous lead extraction.
AB  - BACKGROUND: An arteriovenous (AV) fistula is an infrequently reported
      complication of transvenous lead extraction (TLE), but may be under-recognized.
      OBJECTIVE: To determine the incidence, management, and outcomes of the AV fistula
      complicating TLE. METHODS: All TLE procedures from July 2001 to December 2012
      were reviewed. RESULTS: Of 2471 patients who underwent TLE, the AV fistula
      occurred in 8 (0.3%; 6 pacemaker and 2 implantable cardioverter-defibrillator)
      procedures. Patients who developed an AV fistula had longer lead implant duration
      (11.8 [interquartile range 7.7] vs 5.2 [interquartile range 7.0] years) and were
      more likely to have required a powered sheath (8 of 8 [100%] vs 1392 of 2463
      [56.5%]) compared to those who did not. Other procedural and demographic details
      did not discriminate. All patients had a continuous bruit along the anterior
      chest wall. Catheter angiography was more sensitive (100%) than computed
      tomography (75%) or ultrasound (25%) for confirming the diagnosis and identifying
      the vessels involved. One fistula closed spontaneously, while others were closed
      with covered stents (4) or surgical glue (1). One attempt at closure failed, and
      one was diagnosed postmortem. Mortality related to the AV fistula was 3 of 8
      (37.5%). Patients who died all had structural heart disease. In the 5 patients
      with normal hearts, the AV fistula was well tolerated for up to 2 years.
      CONCLUSIONS: An AV fistula is an infrequent, though possibly under-recognized,
      complication of TLE. It requires a high index of suspicion for early diagnosis,
      may present late, and may be associated with significant morbidity and mortality
      in patients with structural heart disease.

PMID- 24291413
TI  - Selective inhibition of late sodium current suppresses ventricular tachycardia
      and fibrillation in intact rat hearts.
AB  - BACKGROUND: Enhanced late inward Na current (INa-L) modulates action potential
      duration (APD) and plays a key role in the genesis of early afterdepolarizations
      (EADs) and delayed afterdepolarizations (DADs) and triggered activity. OBJECTIVE:
      The purpose of this study was to define the influence of selective block of INa-L
      on EAD- and DAD-mediated triggered ventricular tachycardia (VT) and ventricular
      fibrillation (VF) in intact hearts using (GS967), a selective and potent (IC50 =
      0.13 +/- 0.01 MUM) blocker of INa-L. METHODS: VT/VF were induced either by local
      aconitine injection (50 MUg) in the left ventricular muscle of adult (3-4 months)
      male rats (N = 21) or by arterial perfusion of 0.1 mM hydrogen peroxide (H2O2) in
      aged male rats (24-26 months, N = 16). The left ventricular epicardial surface of
      the isolated-perfused hearts was optically mapped using fluorescent voltage
      sensitive dye, and microelectrode recordings of action potentials were made
      adjacent to the aconitine injection site. The suppressive and preventive effects
      of GS967 (1 MUM) against EAD/DAD-mediated VT/VF were then determined. RESULTS:
      Aconitine induced VT in all 13 hearts studied. Activation map (N = 6) showed that
      the VT was initiated by a focal activity arising from the aconitine injection
      site (cycle length [CL] 84 +/- 12) that degenerated to VF (CL 52 +/- 8 ms) within
      a few seconds. VF was maintained by multifocal activity with occasional
      incomplete reentrant wavefronts. Administration of GS967 suppressed the VT/VF in
      10 of 13 hearts (P < .001). Preexposure to GS967 for 15 minutes before aconitine
      injection prevented initiation of VT/VF in 5 of 8 additional hearts (P < .02). VF
      reoccurred within 10 minutes on washout of GS967. Microelectrode recordings (N =
      7) showed that VT/VF was initiated by EAD- and DAD-mediated triggered activity at
      CL of 86 +/- 14 ms (NS from VT CL) that preceded the VF. GS967 shortened APD,
      flattened the slope of the dynamic APD restitution curve, and reduced APD
      dispersion from 42 +/- 12 ms to 8 +/- 3 ms (P < .01). H2O2 perfusion in eight
      fibrotic aged hearts promoted EAD-mediated focal VT/VF, which was suppressed by
      GS967 in five hearts (P < .02). CONCLUSION: The selective INa-L blocker GS967
      effectively suppresses and prevents aconitine and oxidative stress-induced EADs,
      DADs, and focal VT/VF. Suppression of EADs, DADs, and reduction of APD dispersion
      make GS967 a potentially useful antiarrhythmic drug in conditions of enhanced INa
      L.

PMID- 24291415
TI  - Hsa-miR-196a2 polymorphism increases the risk of acute lymphoblastic leukemia in
      Chinese children.
AB  - Acute lymphoblastic leukemia (ALL) is a major cause of mortality and morbidity in
      childhood, and the causes of ALL are not completely understood. microRNAs
      (miRNAs) regulate various biological processes including organ development, cell
      growth regulation, cell differentiation, apoptosis, and tumorigenesis. We
      performed a case-control study with 570 childhood ALL cases and 673 cancer-free
      controls to investigate the association between hsa-miR-196a2 rs11614913 T>C
      polymorphism and ALL risk. The bioinformatics was used to estimate the potential
      target of hsa-miR-196a2. In the present study, the hsa-miR-196a2 variant TC
      heterozygote, and CC/TC genotypes were found to be associated with a
      significantly increased childhood ALL risk, compared with the TT wild-type
      homozygote (adjusted OR=1.50, 95% CI=1.15-1.95 for TC and OR=1.40, 95% CI=1.09
      1.79 for CC/TC). Further, the difference was pronounced in younger (<=6) subjects
      or parental non-drinker. The significance of the increased risk is more obvious
      than the higher treatment branch. Additionally, we found that the rs11614913 TC
      genotype can increase B-phenotype ALL risk (OR=1.37, 95% CI=1.07-1.76). Finally,
      combination of three bioinformatics approaches revealed that HOXC8 may be the
      target gene of hsa-miR-196a2. Taken together, our finding suggested that hsa-miR
      196a2 rs11614913 T>C may increase the risk of childhood ALL. Large studies with
      the function of hsa-miR-196a2 are needed in the further study.

PMID- 24291416
TI  - Sexual dimorphic effect in the genetic association of monoamine oxidase A (MAOA)
      markers with autism spectrum disorder.
AB  - Autism spectrum disorders are heritable and behaviorally-defined
      neurodevelopmental disorders having skewed sex ratio. Serotonin as modulator of
      behavior and implication of serotonergic dysfunction in ASD etiology corroborates
      that serotonergic system genes are potential candidates for autism
      susceptibility. In the current study X-chromosomal gene, MAOA responsible for
      degradation of serotonin is investigated for possible association with ASD using
      population-based approach. Study covers analysis of 8 markers in 421 subjects
      including cases and ethnically-matched controls from West Bengal. MAOA marker,
      rs6323 and various haplotypes formed between the markers show significant
      association with the disorder. Stratification on the basis of sex reveals
      significant genetic effect of rs6323 with low activity T allele posing higher
      risk in males, but not in females. Haplotypic association results also show
      differential effect both in males and females. Contrasting linkage disequilibrium
      pattern between pair of markers involving rs6323 in male cases and controls
      further supports the sex-bias in genetic association. Bioinformatic analysis
      shows presence of Y-encoded SRY transcription factor binding sites in the
      neighborhood of rs1137070. C allele of rs1137070 causes deletion of GATA-2
      binding site and GATA-2 is known to interact with SRY. This is the first study
      highlighting male-specific effect of rs6323 marker and its haplotypes in ASD
      etiology and it suggests sexual dimorphic effect of MAOA in this disorder.
      Overall results of this study identify MAOA as a possible ASD susceptibility
      locus and the differential genetic effect in males and females might contribute
      to the sex ratio differences and molecular pathology of the disorder. 

PMID- 24291418
TI  - Combination therapy of cyclophosphamide and Rhizoma Paridis Saponins on anti
      hepatocarcinoma mice and effects on cytochrome p450 enzyme expression.
AB  - Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis,
      showed strong activity against lung cancer and hepatocarcinoma. In this research,
      a combination of RPS with cyclophosphamide (CTX) was used to treat
      hepatocarcinoma in mice. Although no active enhancement of activity was observed,
      some attenuation of the toxicity of RPS in combination with CTX occurred. In
      order to explain this phenomenon, we carried out research on the effects of
      Rhizoma Paridis Saponins on the activities of cytochrome p450 enzymes CYP1A2,
      CYP2A6, CYP2B6, CYP2C9, CYP2E1 and CYP3A4. The results indicated that RPS
      significantly influenced the activity of CYP2B6 and CYP3A4 through the inhibition
      of protein expression. However, RPS did not affect the activity of CYP1A2,
      CYP2A6, CYP2C9 and CYP2E1 in rats in vivo. These results suggested that RPS
      inhibited the conversion of cyclophosphamide into active metabolites and inactive
      byproducts through the reduced activities of CYP2B6 and CYP3A4. Therefore, it's
      essential to pay attention to CYP2B6- and CYP3A4-mediated herb-drug interactions
      between RPS and other drugs. 

PMID- 24291417
TI  - N-Methyltaurine N-acyl amidated bile acids and deoxycholic acid in the bile of
      angelfish (Pomacanthidae): a novel bile acid profile in Perciform fish.
AB  - Two novel N-acyl amidated bile acids, N-methyltaurine conjugated cholic acid and
      N-methyltaurine conjugated deoxycholic acid, were found to be major biliary bile
      acids in two species of angelfish the regal (Pygoplites diacanthus) and the blue
      girdled (Pomacanthus navarchus) angelfish. The identification was based on their
      having MS and NMR spectra identical to those of synthetic standards. A survey of
      biliary bile acids of 10 additional species of angelfish found 7 with N
      methyltaurine conjugation. In all 12 species, conjugated deoxycholic acid (known
      to be formed by bacterial 7-dehydroxylation of cholic acid) was a major bile
      acid. In all previous studies of biliary bile acids in fish, deoxycholic acid has
      been present in only trace proportions. In addition, bile acid conjugation with N
      methyltaurine has not been detected previously in any known vertebrate. N
      methyltaurine conjugated bile acids are resistant to bacterial deconjugation and
      dehydroxylation, and such resistance to bacterial enzymes should aid in the
      maintenance of high concentrations of bile acids during lipid digestion. Our
      findings suggest that these species of angelfish have a novel microbiome in their
      intestine containing anaerobic bacteria, and describe the presence of N
      methyltaurine conjugated bile acids that are resistant to bacterial attack. 

PMID- 24291419
TI  - Isolation and structural elucidation of novel cholestane glycosides and
      spirostane saponins from Polygonatum odoratum.
AB  - Much attention has been paid to cholestane-type steroidal glycosides because of
      their importance from the perspectives of both chemical diversity and significant
      biological activities. A phytochemical investigation of the rhizomes of
      Polygonatum odoratum (Liliaceae) resulted in the isolation of three novel
      cholestane-type steroidal glycosides (1-3) with unique Delta(14,16)-unsaturated D
      ring structures as well as two novel spirostane-type steroidal saponins (4 and 5)
      and three known steroidal glycosides (6-8). Their structures were determined by
      various spectroscopic methods and chemical reactions. Steroidal saponin 7 showed
      significant antifungal activity against Candida albicans JCM1542 (MIC 3.1 MUg/mL)
      and Aspergillus fumigatus JCM1738 (MIC 6.3 MUg/mL).

PMID- 24291420
TI  - Photo-cured hyaluronic acid-based hydrogels containing growth and differentiation
      factor 5 (GDF-5) for bone tissue regeneration.
AB  - In this study we describe the generation and influences on in vitro and in vivo
      osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with growth and
      differentiation factor 5 (GDF-5). Prior to loading GDF-5, we characterized the
      release profiles from these hydrogels and tested their respective cell viability,
      differentiation and in vivo bone regeneration. The results from this testing
      indicated that GDF-5 was observed to release in a sustained manner from the HA
      hydrogels I-III. MTT and Live/Dead assays showed that the HA hydrogels I-III have
      good biocompatibility for use as scaffolds for bone tissue regeneration. In vitro
      cell tests showed a higher level of MC3T3-E1 cell proliferation and
      differentiation on HA hydrogels I-III than on HA hydrogel 0. Moreover, in vivo
      animal tests showed that the HA hydrogels I and III had a significant improvement
      on osteogenesis. Overall, our results suggest that the HA-based hydrogel is a
      good biomaterial to deliver osteogenic differentiation factors such as GDF-5, and
      GDF-5 can be useful as an effective alternative to aid new bone formation. 

PMID- 24291421
TI  - Water residing in small ultrastructural spaces plays a critical role in the
      mechanical behavior of bone.
AB  - Water may affect the mechanical behavior of bone by interacting with the mineral
      and organic phases through two major pathways: i.e. hydrogen bonding and polar
      interactions. In this study, dehydrated bone was soaked in several solvents (i.e.
      water, heavy water (D2O), ethylene glycol (EG), dimethylformamide (DMF), and
      carbon tetrachloride(CCl4)) that are chemically harmless to bone and different in
      polarity, hydrogen bonding capability and molecular size. The objective was to
      examine how replacing the original matrix water with the solvents would affect
      the mechanical behavior of bone. The mechanical properties of bone specimens
      soaked in these solvents were measured in tension in a progressive loading
      scheme. In addition, bone specimens without any treatments were tested as the
      baseline control whereas the dehydrated bone specimens served as the negative
      control. The experimental results indicated that 22.3+/-5.17vol% of original
      matrix water in bone could be replaced by CCl4, 71.8+/-3.77vol% by DMF, 85.5+/
      5.15vol% by EG, and nearly 100% by D2O and H2O, respectively. CCl4 soaked
      specimens showed similar mechanical properties with the dehydrated ones. Despite
      of great differences in replacing water, only slight differences were observed in
      the mechanical behavior of EG and DMF soaked specimens compared with dehydrated
      bone samples. In contrast, D2O preserved the mechanical properties of bone
      comparable to water. The results of this study suggest that a limited portion of
      water (<15vol% of the original matrix water) plays a pivotal role in the
      mechanical behavior of bone and it most likely resides in small matrix spaces,
      into which the solvent molecules larger than 4.0A cannot infiltrate. 

PMID- 24291422
TI  - The major egg reserve protein from the invasive apple snail Pomacea maculata is a
      complex carotenoprotein related to those of Pomacea canaliculata and Pomacea
      scalaris.
AB  - Snails from the genus Pomacea lay conspicuous masses of brightly colored eggs
      above the water. Coloration is given by carotenoproteins that also which play
      important roles in protection against sun radiation, stabilizing and transporting
      antioxidant molecules and helping to protect embryos from desiccation and
      predators. They seem a key acquisition, but have been little studied. Here we
      report the characteristics of the major carotenoprotein from Pomacea maculata and
      the first comparison among these egg proteins. This particle, hereafter PmPV1,
      represents ~52% of perivitellin fluid protein. It is a glyco-lipo-carotenoprotein
      responsible for the bright reddish egg coloration. With VHDL characteristics,
      PmPV1 apparent molecular mass is 294kDa, composed of five non-covalently bound
      subunits of pI 4.7-9.8 and masses between 26 and 36kDa whose N-terminal sequences
      were obtained. It is a glyco-lipo-carotenoprotein scarcely lipidated (<1%) but
      highly glycosilated (13% by wt). Lipids include phospholipids, free fatty acids
      and carotenoids; mannose and galactose predominate over other monosaccharides.
      Main carotenoids are esterified and non-esterified astaxanthin (71 and 25%,
      respectively). Carotenoid removal does not seem to affect the structural
      characteristics of the oligomer, while deglycosilation reduces subunit number
      from five to a single one. The carotenoid-protein association protected the
      former against oxidation. PmPV1 cross reacts with polyclonal antibodies against
      the PcOvo, the major carotenoprotein from Pomacea canaliculata. The
      characterization of PmPV1 allows the first comparisons among snail
      carotenoproteins and further highlights the importance of these perivitellins in
      the reproductive strategy of Pomacea. 

PMID- 24291423
TI  - The shell organic matrix of the crossed lamellar queen conch shell (Strombus
      gigas).
AB  - In molluscs, the shell organic matrix comprises a large set of biomineral
      occluded proteins, glycoproteins and polysaccharides that are secreted by the
      calcifying mantle epithelium, and are supposed to display several functions
      related to the synthesis of the shell. In the present paper, we have
      characterized biochemically the shell matrix associated to the crossed-lamellar
      structure of the giant queen conch Strombus gigas. The acid-soluble (ASM) and
      acid-insoluble (AIM) matrices represent an extremely minor fraction of the shell.
      Both are constituted of polydisperse and of few discrete proteins among which
      three fractions, obtained by preparative SDS-PAGE and named 1P3, 2P3 and 3P3, are
      dominant and were further characterized. Compared to other matrices, the acid
      soluble matrix is weakly glycosylated (3%) and among the discrete components,
      only 3P3 seems noticeably glycosylated. The monosaccharide composition of the ASM
      shows that mannose represents the main monosaccharide. To our knowledge, this is
      the first report of a high ratio of this sugar in a skeletal matrix. Furthermore,
      the ASM interacts with the in vitro crystallization of calcium carbonate, but
      this interaction is moderate. It differs from that of the isolated 1P3 fraction
      but is similar to that of the 2P3 and 3P3 fractions. At last, antibodies
      developed from the 3P3 fraction were used to localize this fraction within the
      shell by immunogold. This study is the first one aiming at characterizing the
      organic matrix associated to the crossed-lamellar structure of the queen conch
      shell. 

PMID- 24291424
TI  - FT-IR, FT-Raman and DFT quantum chemical study on the molecular conformation,
      vibrational and electronic transitions of 1-(m
      (trifluoromethyl)phenyl)piperazine.
AB  - The FTIR and FT-Raman spectra of 1-(m-(trifluoromethyl)phenyl)piperazine [TFMPP]
      have been recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1),
      respectively. The optimized geometry, frequency and intensity of the vibrational
      bands of the compound was obtained by the density functional theory using 6
      311++G(d,p) basis set. The harmonic vibrational frequencies were calculated and
      the scaled values have been compared with experimental FTIR and FT-Raman spectra.
      The observed and the calculated frequencies are found to be in good agreement. A
      detailed interpretation of the infrared and Raman spectra were also reported
      based on potential energy distribution (PED). UV-Vis spectrum of the compound was
      recorded and the electronic properties HOMO and LUMO energies were measured by TD
      DFT approach. Furthermore, molecular electrostatic potential is performed and
      also the calculated HOMO and LUMO energies show that charge transfer occurs
      within the molecule.

PMID- 24291425
TI  - Experimental and DFT studies on the vibrational and electronic spectra and NBO
      analysis of 2-amino-3-((E)-(9-p-tolyl-9H-carbazol-3-yl) methyleneamino)
      maleonitrile.
AB  - 2-Amino-3-((E)-(9-p-tolyl-9H-carbazol-3-yl) methyleneamino) maleonitrile (ACMM)
      was synthesized and characterized by X-ray diffraction, FT-IR, FT-Raman and UV
      Vis spectra. The X-ray diffraction study showed that ACMM has a Z-configuration,
      due to the intramolecular C18H18A?N2, N3H3A?N2 and C20H20A?N4 hydrogen bonds and
      intermolecular C10H10A?N4, N3H3B?N9 (2-x, 2-y, 2-z) and N3H8C?N4 (2-x, 1-y, 2-z)
      hydrogen bonds. The benzene ring including methyl is twisted from the mean plane
      of the carbazole group by 59.7(3) degrees . Vibrational spectra and electronic
      spectra measurements were made for the compound. Optimized geometrical structure
      and harmonic vibrational frequencies were computed with DFT (B3-based B3P86,
      B3LYP, B3PW91 and B-based BP86, BLYP, BPW91) methods and ab initio RHF method
      using 6-311++G(d, p) basis set. Assignments of the observed spectra were
      proposed. The equilibrium geometries computed by all of the methods were compared
      with X-ray diffraction results. The absorption spectra of the title compound were
      computed both in gas phase and in DMF solution using TD-B3LYP/6-311++G(d, p) and
      PCM-B3LYP/6-311++G(d, p) approaches, respectively. The calculated results provide
      a good description of positions of the bands maxima in the observed electronic
      spectrum. Temperature dependence of thermodynamic parameters in the range of 100
      1000K were determined. The bond orbital occupancies, contribution from parent
      natural bond orbital (NBO), the natural atomic hybrids was calculated and
      discussed. 

PMID- 24291426
TI  - Investigations on the growth aspects and characterization of semiorganic
      nonlinear optical single crystals of L-histidine and its hydrochloride
      derivative.
AB  - Semiorganic single crystals of l-histidine and l-histidine hydrochloride
      monohydrate have been obtained in a single solution prepared from the mixture of
      l-histidine and hydrochloric acid in 1:2M ratio. Growth aspects of the single
      crystals have been discussed along with characterization studies. Crystal system
      and lattice parameters have been identified by X-ray diffraction analyses. It has
      been observed that the grown crystals possess orthorhombic system but with
      different set of lattice parameters. Presence of various functional groups has
      been identified and formation of two different crystals has been confirmed by
      Fourier transform infrared spectral analyses and FT-Raman studies. Linear and
      nonlinear optical properties have been studied by UV-Vis spectral analyses and
      Kurtz-Perry powder technique respectively. The thermal stability of the grown
      crystals was determined by thermal analyses. From the characterization studies it
      is found that both the crystals are useful for second harmonic generation
      applications. 

PMID- 24291427
TI  - A highly selective fluorescent chemosensor for iron ion based on 1H-imidazo [4,5
      b] phenazine derivative.
AB  - Two kinds of fluorescent sensors (S and S1) for Fe(3+) bearing 1H-Imidazo [4,5-b]
      phenazine derivatives have been designed and synthesized. Between the two
      sensors, S showed excellent fluorescent specific selectivity and high sensitivity
      for Fe(3+) in DMSO solution. The test strip based on S was fabricated, which
      could act as a convenient and efficient Fe(3+) test kit. The recognition
      mechanism of the sensor toward Fe(3+) was evaluated by MS, IR and XRD. The
      detection limit of the sensor S towards Fe(3+) is 4.8*10(-6)M. And other cations,
      including Hg(2+),Ag(+), Ca(2+), Cu(2+), Co(2+), Ni(2+), Cd(2+), Pb(2+), Zn(2+),
      Cr(3+), and Mg(2+) had no influence on the probing behavior. 

PMID- 24291428
TI  - Fluorescent chemosensor based on sensitive Schiff base for selective detection of
      Zn2+.
AB  - A Schiff-base fluorescent compound - N, N'-bis(salicylidene)-1,2 -
      phenylenediamine (LH2) was synthesized and evaluated as a chemoselective Zn(2+)
      sensor. Addition of Zn(2+) to ethanol solution of LH2 resulted in a red shift
      with a pronounced enhancement in the fluorescence intensity. 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+). Fluorescence studies on free Schiff base ligand LH2 and LH2 -
      Zn(2+) complex reveal that the quantum yield strongly increases upon
      coordination. 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- 24291429
TI  - Direct colorimetric biosensing of mercury(II) ion based on aggregation of poly
      (gamma-glutamic acid)-functionalized gold nanoparticles.
AB  - A simple and sensitive method for colorimetric detection of mercury ion (Hg(2+))
      has been developed by using a poly (gamma-glutamic acid) functionalized gold
      nanoparticles (PGA-AuNPs) system. Electrostatic self-assembly technique was used
      to assemble negatively charged PGA on the surface of positively charged CTAB
      capped AuNPs. With the increase of Hg(2+) concentration, the color of the
      solution would progress from light red to purple blue. The results showed that
      the absorbance ratio (A750/A580) was linear with the Hg(2+) concentration in the
      range of 0.01-10 MUM and from 50 to 300 MUM, with the correlation coefficients of
      0.998 and 0.991, respectively. The reported probe is suitable for real-time
      detection of Hg(2+) in water with the limit of detection (LOD) of 1.9 nM obtained
      by UV-vis spectrum, and exhibits selectivity toward one order of magnitude over
      other metal ions. This approach was applied successfully to the determination of
      Hg(2+) in tap water and mineral water, and the recoveries were from 90% to 103%
      and from 103.53% to 113%, respectively. The proposed method is rapid, low-cost
      and free of complex equipment, making it possible to analyze Hg(2+) in various
      water samples.

PMID- 24291430
TI  - Molecular structure, tautomeric stability, protonation and deprotonation effects,
      vibrational, NMR and NBO analyses of 2,4-Dioxoimidazolidine-5-acetic acid (DOIAA)
      by quantum chemical calculations.
AB  - This study represents the conformation, tautomeric stability, protonation and
      deprotonation effects, vibrational, electronic, NBO and NMR aspects of 2,4
      Dioxoimidazolidine-5-acetic acid (DOIAA). Theoretical calculations were performed
      by ab initio HF and density functional theory (DFT)/B3LYP method using 6
      311++G(d,p) basis sets. Tautomerism and the effect of solvent on the tautomeric
      equilibria in the gas phase and in different solvents were studied. The
      protonation and deprotonation effects on the reactivity and conformations of
      DOIAA were investigated. Electronic transitions were also studied and the most
      prominent transition corresponds to pi->pi*. Natural bond orbital (NBO) analysis
      was also carried out to find the intramolecular interactions and their
      stabilization energy. In DOIAA, the interaction between the lone pair donor
      orbital (n(LP1N5)) and the acceptor antibonding orbital pi*(C6O7) reveals the
      strong stabilization energy of 224.9 kJ mol(-1). Molecular electrostatic
      potential (MEP) was calculated to predict the reactive sites of the title
      compound. The NMR results indicated that the observed chemical shifts for NH,
      COOH protons of DOIAA not only depend on the structure of the molecule being
      studied but also on the nature of the solvent, concentration of the sample and
      the presence of the other exchangeable protons.

PMID- 24291431
TI  - Synthesis and spectral characterizations of trivalent ions (Cr3+, Fe3+) doped CdO
      nanopowders.
AB  - Trivalent transition metal ions (Cr(3+), Fe(3+)) doped CdO nanopowders via
      sonication in the presence of Sodium lauryl sulfate as stabilizing agent were
      synthesized and characterized. Powder XRD studies indicate that the obtained CdO
      has a cubic phase and concluded that the trivalent ions doping induced the
      lattice constants to change some extent. Optical absorption spectra exhibited the
      characteristic bands of Cr(3+) and Fe(3+) ions in octahedral site symmetry.
      Crystal field (Dq) and inter-electronic repulsion (B and C) parameters are
      evaluated for Cr(3+) doped CdO nanopowders as Dq=1540, B=619 and C=3327 cm(-1)
      and for Fe(3+) doped CdO nanopowders Dq=920, B=690, C=2750 cm(-1). EPR spectra of
      the Cr(3+) and Fe(3+) doped CdO nanopowders exhibited resonances at g=1.973 and
      g=2 respectively which indicate distorted octahedral site for both ions with the
      host. Photoluminescence spectra shows the emission bands in violet and bluish
      green regions for Cr(3+) doped CdO, ultraviolet and blue emissions for Fe(3+)
      doped CdO nanopowders. The CIE chromaticity coordinates were also evaluated from
      the emission spectrum. FT-IR spectra indicate the presence of various functional
      groups of host lattice.

PMID- 24291432
TI  - Intramolecular excited proton transfer of 1-(1-phenyl-1H-phenanthro[9,10
      d]imidazol-2-yl)naphthalen-2-ol--a combined experimental and quantum chemical
      studies.
AB  - Synthesis of the 1-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)naphthalen-2-ol
      [PPIN] is reported, spectral and fluorescent properties of the title compound are
      investigated. The feasibility of excited state intramolecular proton transfer
      (ESIPT) has been argued from the changeover of relative stability of the enol and
      the keto forms on photoexcitation from the S0-PES to the S1-PES. Critical
      evaluation on the modulations of geometrical parameters other than the proton
      transfer reaction coordinate has also been undertaken. The intramolecular
      hydrogen bonding (IMHB) interaction in PPIN has been explored by calculation of
      the hyperconjugative charge transfer interaction from the lone electron pair of
      ring nitrogen atom to the sigma(*) orbital of O-H bond, under the provision of
      Natural Bond Orbital (NBO) analysis. However, DFT calculations together with the
      experimental results reveal that the excited species with the intramolecular N?HO
      hydrogen bond type undergoes rapid radiationless deactivation. This leads to a
      conclusion that the low-intensity dual-band fluorescence of the title compound in
      solution originates from the traces of the conformation with the -OH bond to
      azomethine nitrogen atom (ESIPT). 

PMID- 24291433
TI  - Role of charge transfer interaction and the chemical physics behind effective
      fulleropyrrolidine/porphyrin non-covalent interaction in solution.
AB  - The present paper reports the photophysical insights on supramolecular
      interaction of a monoporphyrin derivative, namely, 1, with C60 pyrrolidine tris
      acid ethyl ester (PyC60) in toluene and benzonitrile. The ground state
      interaction between PyC60 and 1 is facilitated through charge transfer
      interaction. Both UV-Vis and steady state measurements elicit almost similar
      magnitude of binding constant for the PyC60/1 complex in toluene and
      benzonitrile, viz., 6825 and 6540 dm(3 )mol(-1), respectively. Life time
      measurement evokes that rate of charge separation is fast in benzonitrile. Both
      hybrid-DFT and DFT calculations provide very good support in favor of electronic
      charge-separation in PyC60/1 system in vacuo.

PMID- 24291434
TI  - Highly selective and sensitive receptor for Fe3+ probing.
AB  - A new fluorescent receptor 1,1'-(4-methylbenzene-1,3-diyl)bis[3-(2
      sulfanylphenyl)urea] (1) has been designed and synthesized. The receptor showed
      excellent selectivity for Fe(3+) in DMSO/H2O (8:2, v/v) solvent system over other
      commonly coexistent metal ions. The binding constant (Ka) of receptor with Fe(3+)
      was calculated to be 11,250 M(-1), 12,970 M(-1) and 12,970 M(-1) using Benesi
      Hildebrand, Scatchard and Connor plot, respectively. The experimental results
      have been further supported by the detailed DFT calculations.

PMID- 24291435
TI  - Theoretical investigations on the molecular structure, vibrational spectra,
      thermodynamics, HOMO-LUMO, NBO analyses and paramagnetic susceptibility
      properties of p-(p-hydroxyphenoxy)benzoic acid.
AB  - The experimental FT-IR (4000-400 cm(-1)) and FT-Raman (3500-100 cm(-1)) spectra
      of p-(p-hydroxyphenoxy) benzoic acid have been recorded. Quantum chemical
      calculations of energies, geometries, and vibrational wavenumbers of p-(p
      hydroxyphenoxy) benzoic acid (PPHPBA) are carried out using HF and DFT/B3LYP
      methods with 6-311G (d,p) basis set. The optimized geometrical parameters
      obtained by B3LYP method show a good agreement with experimental data. The
      difference between the observed and scaled wave number values of most of the
      fundamentals is very small. The complete assignments were performed on the basis
      of the potential energy distribution (PED) of the vibrational modes calculated
      with scaled quantum mechanical method. The calculated HOMO and LUMO energies
      allow the calculation of atomic and molecular properties and they also show that
      charge transfer occurs in the molecule. A detailed molecular picture of PPHPBA
      and its intermolecular interactions were obtained from NBO analysis. The
      temperature dependence of various thermodynamic parameters was also studied. The
      paramagnetic behavior of the molecule under consideration has been investigated
      and the variation of paramagnetic susceptibility with temperature has been
      studied.

PMID- 24291436
TI  - Spectroscopic and structural investigation of 2,5-dicarboxy-1-methylpyridinium
      inner salt.
AB  - The structure of 2,5-dicarboxy-1-methylpyridinium inner salt (1), has been
      studied by X-ray diffraction, B3LYP/6-311G(d,p) calculations, FTIR, Raman and NMR
      spectroscopy. The molecules are linked by short intermolecular and asymmetric O
      H?O hydrogen bonds of 2.486(2)A between carboxyl and carboxylate groups of
      neighboring molecules into infinite chains. The hydrogen bonds in the molecules
      optimized by the B3LYP/6-311G(d,p) approach in trimer (2) and dimer (3) are
      slightly longer than in the crystal. The FTIR spectrum of the investigated inner
      salt is dominated by a broad and intense absorption in the 1500-800 cm(-1) region
      attributed to the nu(as)(OHO) and gamma(OHO) vibrations of the strong hydrogen
      bond. In the Raman spectrum the broad absorption is absent. Linear correlations,
      delta(exp)=a+b sigma(calc) between the experimental (1)H and (13)C NMR chemical
      shifts (delta(exp)) of the investigated inner salt in D2O and the calculated
      magnetic isotropic shielding constants (sigma(calc)) for the optimized monomer
      (4a) solvated in water are reported. The pKa value for 1 of 2.31+/-0.02 was
      determined by the potentiometric titration.

PMID- 24291437
TI  - Surface plasmon resonance optical sensor and antibacterial activities of
      biosynthesized silver nanoparticles.
AB  - Silver nanoparticles were prepared using aqueous fruit extract of Ananas comosus
      as reducing agent. These silver nanoparticles showed surface plasmon peak at 439
      nm. They were monodispersed and spherical in shape with an average particle size
      of 10 nm. The crystallinity of these nanoparticles was evident from clear lattice
      fringes in the HRTEM images and bright circular spots in the SAED pattern. The
      antibacterial activities of prepared nanoparticles were found to be size
      dependent, the smaller nanoparticles showing more bactericidal effect. Aqueous
      Zn(2+) and Cu(4+) selectivity and sensitivity study of this green synthesized
      nanoparticle was performed by optical sensor based surface plasmon resonance
      (SPR) at room temperature.

PMID- 24291438
TI  - Study on polymer fibers doped with phosphorescent Re(I) complex via
      electrospinning: synthetic strategy, structure, morphology and photophysical
      features.
AB  - In the following paper, a Re(I) complex with electron-withdrawing oxadiazole
      group in its diamine ligand (denoted as N-N) was synthesized. Its single crystal
      structure analysis confirmed the successful synthesis of both ligand and complex.
      The central Re(I) ion localized in a traditional octahedral coordination
      environment. The diamine ligand 2-(pyridin-2-yl)-5-(p-tolyl)-1,3,4-oxadiazole
      (denoted as PPOZ) took a coplanar structure and the corresponding face-to-face pi
      pi attraction between PPOZ ligands made the Re(I) complex molecules adjust a
      highly ordered arrangement which was positive to improve emissive performance. In
      order to repress the excited state geometric relaxation and further improve the
      emissive performance, the Re(I) complex was doped into a polymer host
      poly(vinylpyrrolidone) via electrospinning, resulting in composite fibers. The
      morphology of those composite fibers was analyzed by electron microscopy. The
      photophysical comparison between bulk sample and composite fibers indicated that
      the composite fibers showed emission blue shift, longer excited state lifetime
      and improved photostability. Further analysis suggested that the excited state
      geometric relaxation could be effectively repressed when the Re(I) complex
      molecules were immobilized in the polymer matrix, leading to above variations. 

PMID- 24291439
TI  - Identification of archaeological triterpenic resins by the non-separative
      techniques FTIR and 13C NMR: the case of Pistacia resin (mastic) in comparison
      with frankincense.
AB  - The use of spectroscopic techniques such as Fourier-transform infrared (FTIR)
      spectroscopy and carbon 13 nuclear magnetic resonance ((13)C NMR) using the J-mod
      experiment is proposed as an effective alternative to gas chromatography-mass
      spectrometry (GC-MS) for the analysis and identification of natural resin samples
      found in archaeological environments. The spectral features of the most common
      diterpenic and triterpenic resins and also two gum-resins are reported and
      discussed for both techniques. The analytical procedure based on the combined use
      of FTIR and (13)C NMR is then applied to two archaeological samples from the
      Milano of the Roman age allowing their identification as Pistacia resin, or
      mastic, as confirmed by the traditional GC-MS method, and also elucidating some
      effects of aging on such material. 

PMID- 24291440
TI  - Physiological and ecological significance of biomineralization in plants.
AB  - Biomineralization is widespread in the plant kingdom. The most common types of
      biominerals in plants are calcium oxalate crystals, calcium carbonate, and
      silica. Functions of biominerals may depend on their shape, size, abundance,
      placement, and chemical composition. In this review we highlight advances in
      understanding physiological and ecological significance of biomineralization in
      plants. We focus on the functions of biomineralization in regulating cytoplasmic
      free calcium levels, detoxifying aluminum and heavy metals, light gathering and
      scattering to optimize photosynthesis, aiding in pollen release, germination, and
      tube growth, the roles it plays in herbivore deterrence, biogeochemical cycling
      of carbon, calcium, and silicon, and sequestering atmospheric CO2. 

PMID- 24291441
TI  - Mechanism of matrix metalloproteinase axis-induced neointimal growth.
AB  - Tumor necrosis factor-alpha, platelet-derived growth factor, matrix
      metalloproteinases 9 and 2 have very important roles in neointimal hyperplasia,
      which develops after endovascular injury. However, the relationships among the
      four factors in inducing neointimal hyperplasia are unclear. Here, we used a
      mouse model of femoral arterial transluminal wire injury, and examined neointimal
      hyperplasia within the 28 days that followed the injury. We confirmed that the
      neointima kept growing during the 28 days, and found that expression of TNF-alpha
      and PDGF mRNAs in femoral arteries peaked within 24h after injury. However, MMP9
      mRNA expression peaked 7 days, and MMP2 mRNA expression peaked 28 days after
      injury. Then, we administered exogenous TNF-alpha or PDGF to the peri-femoral
      artery following an injury, and found that exogenous TNF-alpha led to
      significantly more neointimal hyperplasia during the first 2 weeks, and PDGF led
      to increased neointimal hyperplasia during the second 2 weeks after injury. We
      also used the model of femoral artery injury in MMP9- or MMP2-deficient (MMP9-/-
      or MMP2-/-) mice. We found that neointimal hyperplasia was reduced in MMP9-/-
      mice during the first 2 weeks after injury, and neointimal hyperplasia was
      reduced in MMP2-/- mice during the second 2 weeks after injury. When TNF-alpha or
      PDGF was administered to the peri-femoral artery immediately after injury, TNF
      alpha did not promote neointimal hyperplasia in MMP9-/- mice during the first 2
      weeks after injury but did in MMP2-/- mice, and PDGF did not promote neointimal
      hyperplasia in MMP2-/- mice during the second 2 weeks after injury but did in
      MMP9-/- mice. We used an in vitro system to treat vascular smooth muscle cells
      (VSMCs) with TNF-alpha or PDGF; TNF-alpha induced MMP9, but not MMP2, expression
      at a fast reaction speed, while PDGF induced MMP2, but not MMP9, expression at a
      slow reaction speed. Meanwhile, TNF-alpha induced VSMC migration in a MMP9
      dependent manner, and PDGF induced VSMC proliferation in a MMP2-dependent manner.
      Taken together, our studies elucidated the axis of TNF-alpha-MMP9-VSMC migration
      and PDGF-MMP2-VSMC proliferation, both of which contributed to the mechanism of
      neointimal hyperplasia formation.

PMID- 24291442
TI  - Lesions of the posterior glottis: clinical and pathologic considerations and
      treatment outcome.
AB  - OBJECTIVE: To assess the clinical profile, presentation, prognosis, and response
      to treatment of patients with posterior glottic lesions and the prevalence of
      malignancy in this group. STUDY DESIGN: Retrospective cohort. METHODS: Studying
      medical records, videostroboscopic examinations, and pathologic reports of
      patients diagnosed and treated between 2008 and 2011. RESULTS: Forty-six patients
      had lesions limited to the posterior glottis. Forty-one of the cases were
      diagnosed clinically or pathologically as inflammatory granulation tissue; three
      were cysts; one carcinoma in situ; and one invasive squamous cell carcinoma. Of
      the inflammatory granulation patients, 71% had lesions defined as spontaneous and
      29% were considered iatrogenic. Reflux symptoms and reflux signs, as well as
      psychological stress were significantly more prevalent in the spontaneous group.
      Fifty percent of the patients with spontaneous lesions had psychological stress,
      compared with 8% in the iatrogenic group (P value = 0.009). Smoking was a
      significant risk factor in the iatrogenic group (54% vs 21% P value = 0.03). Nine
      percent of the lesions were treated with primary surgery. Ninety-one percent were
      treated with primary conservative management, of whom 31% were eventually
      referred to surgery. Overall, 91% of the patients were treated successfully. All
      cases of iatrogenic lesions responded to conservative management or a single
      surgical intervention. All patients that required multiple interventions were
      spontaneous. CONCLUSIONS: The results of this study suggest that only a small
      percent of posterior glottic lesions are malignant, thus the decision about
      biopsy should be based on clinical judgment. Also, spontaneous granulomas are
      more refractory to treatment, which can be explained by the repetitive exposure
      to the etiologic factors.

PMID- 24291443
TI  - Vocal fold paralysis secondary to phonotrauma.
AB  - A unique case of acute onset vocal fold paralysis secondary to phonotrauma is
      presented. The cause was forceful vocalization by a drill instructor on a firearm
      range. Imaging studies revealed extensive intralaryngeal and retropharyngeal
      hemorrhage. Laryngoscopy showed a complete left vocal fold paralysis. Relative
      voice rest was recommended, and the patient regained normal vocal fold mobility
      and function after approximately 12 weeks. 

PMID- 24291444
TI  - The effect of singing training on voice quality for people with quadriplegia.
AB  - OBJECTIVES: Despite anecdotal reports of voice impairment in quadriplegia, the
      exact nature of these impairments is not well described in the literature. This
      article details objective and subjective voice assessments for people with
      quadriplegia at baseline and after a respiratory-targeted singing intervention.
      STUDY DESIGN: Randomized controlled trial. METHODS: Twenty-four participants with
      quadriplegia were randomly assigned to a 12-week program of either a singing
      intervention or active music therapy control. Recordings of singing and speech
      were made at baseline, 6 weeks, 12 weeks, and 6 months postintervention. These
      deidentified recordings were used to measure sound pressure levels and assess
      voice quality using the Multidimensional Voice Profile and the Perceptual Voice
      Profile. RESULTS: Baseline voice quality data indicated deviation from normality
      in the areas of breathiness, strain, and roughness. A greater percentage of
      intervention participants moved toward more normal voice quality in terms of
      jitter, shimmer, and noise-to-harmonic ratio; however, the improvements failed to
      achieve statistical significance. CONCLUSIONS: Subjective and objective
      assessments of voice quality indicate that quadriplegia may have a detrimental
      effect on voice quality; in particular, causing a perception of roughness and
      breathiness in the voice. The results of this study suggest that singing training
      may have a role in ameliorating these voice impairments.

PMID- 24291445
TI  - Expression, purification and anticancer analysis of GST-tagged human perforin and
      granzyme B proteins in human laryngeal cancer Hep-2 cells.
AB  - Granzyme B and perforin, two major effector molecules in the granule-mediated
      cytolytic pathway, are thought to be involved in suppression of tumor
      progression. In this study, the pGEX-4T-1 expression vector was used to express
      full-length human perforin or granzyme B as a GST-tagged fusion protein in
      Escherichia coli (E. coli). GST-tagged proteins were induced with IPTG and
      purified by GSTrap 4B columns. Purified fusion proteins migrated at the predicted
      molecular mass on SDS-PAGE and were recognized by specific antibodies. Moreover,
      the fusion proteins can induce apoptosis and directly inhibit the growth of human
      laryngeal cancer Hep-2 cells in vitro. These results suggest that active perforin
      and granzyme B fusion proteins can be produced in E. coli and exhibit anticancer
      potential in laryngeal cancer cells. 

PMID- 24291446
TI  - Recombinant production of Epstein-Barr virus BZLF1 trans-activator and
      characterization of its DNA-binding specificity.
AB  - This paper describes the recombinant production of a biologically active Epstein
      Barr virus BZLF1 trans-activator, i.e., Z-encoded broadly reactive activator
      (ZEBRA), that recognized specific DNA motifs. We used auto-induction for
      histidine-tagged BZLF1 expression in Escherichia coli and immobilized cobalt
      affinity membrane chromatography for protein purification under native
      conditions. We obtained the purified BZLF1 at a yield of 5.4mg per gram of wet
      weight cells at 75% purity, in which 27% of the recombinant BZLF1 remained
      biologically active. The recombinant BZLF1 bound to oligonucleotides containing
      ZEBRA response elements, either AP-1 or ZIIIB, but not a ZIIIB mutant. The
      recombinant BZLF1 showed a specific DNA-binding activity which could be useful
      for functional studies. 

PMID- 24291447
TI  - Stair-specific algorithms for identification of touch-down and foot-off when
      descending or ascending a non-instrumented staircase.
AB  - The present study introduces four event detection algorithms for defining touch
      down and foot-off during stair descent and stair ascent using segmental
      kinematics. For stair descent, vertical velocity minima of the whole body center
      of-mass was used to define touch-down, and foot-off was defined as the instant of
      trail limb peak knee flexion. For stair ascent, vertical velocity local minima of
      the lead-limb toe was used to define touch-down, and foot-off was defined as the
      local maxima in vertical displacement between the toe and pelvis. The performance
      of these algorithms was determined as the agreement in timings of kinematically
      derived events to those defined kinetically (ground reaction forces). Data were
      recorded while 17 young and 15 older adults completed stair descent and ascent
      trials over a four-step instrumented staircase. Trials were repeated for three
      stair riser height conditions (85 mm, 170 mm, and 255 mm). Kinematically derived
      touch-down and foot-off events showed good agreement (small 95% limits of
      agreement) with kinetically derived events for both young and older adults,
      across all riser heights, and for both ascent and descent. In addition, agreement
      metrics were better than those returned using existing kinematically derived
      event detection algorithms developed for overground gait. These results indicate
      that touch-down and foot-off during stair ascent and descent of non-instrumented
      staircases can be determined with acceptable precision using segmental kinematic
      data.

PMID- 24291448
TI  - Vibrational and UV spectra, first order hyperpolarizability, NBO and HOMO-LUMO
      analysis of 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl-benzamide.
AB  - In this work, the vibrational spectral analysis was carried out by using FT-Raman
      and FT-IR spectroscopy in the range 4000-100 cm(-1) and 4000-400 cm(-1),
      respectively, for 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl
      benzamide (C16H16O3N3SCl) molecule. Theoretical calculations were performed by
      density functional theory (DFT) method using 6-31G(d,p) and 6-311G(d,p) basis
      sets. The complete vibrational assignments of wavenumbers were made on the basis
      of potential energy distribution (PED). The results of the calculations were
      applied to simulated spectra of the title compound, which show excellent
      agreement with observed spectra. The frontier orbital energy gap and dipole
      moment illustrates the high reactivity of the title molecule. The first order
      hyperpolarizability (beta0) and related properties (MU, alpha, and Deltaalpha) of
      the molecule were also calculated. Stability of the molecule arising from
      hyperconjugative interactions and charge delocalization has been analyzed using
      natural bond orbital (NBO) analysis. The UV-vis spectrum of the compound was
      recorded in the region 200-400 nm in ethanol and electronic properties such as
      excitation energies, oscillator strength and wavelength were calculated by TD
      DFT/B3LYP method. Molecular electrostatic potential (MEP) and HOMO-LUMO energy
      levels are also constructed. The thermodynamic properties of the title compound
      were calculated at different temperatures.

PMID- 24291449
TI  - Quantum chemical investigations on the effect of dodecyloxy chromophore in 4
      amino stilbene sensitizer for DSSCs.
AB  - Stilbene based metal free organic dye sensitizer has been designed first time for
      dye sensitized solar cells applications. The geometries, electronic structures
      and dipole moment of the chosen 4-amino-4'-dodecyloxy-stilbene dye sensitizer has
      been analyzed by using Density Functional Theory (DFT) and Time Dependent DFT (TD
      DFT) calculations (based on hybrid functional B3LYP). The HOMO and LUMO energies
      of the dye 4-amino-4'-dodecyloxy-stilbene are -4.95 and -0.87 eV respectively
      calculated by using TD-DFT. To understand the conversion efficiency of the chosen
      dye architecture unit we selected TiO2 as a model for semiconductor. The values
      of polarizability and hyperpolarizability are 165. 94 and 347.74 a.u respectively
      based on DFT calculations. Results reveal that the selected dye sensitizer
      exhibits large dipole moment difference between the ground and excited state
      which is comparable to that of metal based dye sensitizers. Further the large
      dipole moment would be expected to give high photo-current conversion efficiency
      in practical DSSCs and also it is a promising candidate as a sensitizer for DSSC
      applications.

PMID- 24291451
TI  - Mechanism for the protective effect of diallyl disulfide against cyclophosphamide
      acute urotoxicity in rats.
AB  - This study investigated the protective effects of diallyl disulfide (DADS)
      against cyclophosphamide (CP)-induced acute urotoxicity in rats. CP caused severe
      hemorrhagic cystitis as shown by significant increases in bladder weight, edema,
      and hemorrhage as well as increased urinary bladder epithelial cell apoptosis,
      protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and
      phase II enzymes (i.e., NAD(P)H: quinone oxidoreductase-1 (NQO-1) and heme
      oxygenase-1 (HO-1)), immunostaining intensity of acrolein-protein adducts, and
      histopathological changes. The significant decreases in glutathione content and
      catalase, glutathione-S-transferase, and glutathione reductase activities and a
      significant increase in malondialdehyde content indicated that CP-induced bladder
      injury was mediated through oxidative stress. In contrast, pretreatment with DADS
      significantly attenuated the CP-induced urotoxic effects, including oxidative
      damage, histopathological lesions, apoptotic changes, and accumulation of
      acrolein-protein adducts in the bladder. DADS also significantly increased
      expression of CYP2B1/2, CYP3A1, Nrf-2, NQO-1, and HO-1 and significantly
      decreased expression of CYP2C11. These results indicate that DADS prevented CP
      induced bladder toxicity, in part, by detoxifying acrolein. The protective
      effects of DADS may be due to its ability to decrease metabolic activation of CP
      by inhibiting CYP2C11 and inducing CYP3A1, and its potent antioxidant activity
      and antiapoptotic effects occurred via the Nrf-2-antioxidant response element
      pathway.

PMID- 24291450
TI  - A new ternary copper(II) complex derived from 2-(2'-pyridyl)benzimidazole and
      glycylglycine: synthesis, characterization, DNA binding and cleavage,
      antioxidation and HSA interaction.
AB  - A new ternary copper(II)-dipeptide complex [Cu(glygly)(HPB)(Cl)]?2H2O
      (glygly=glycylglycine anion, HPB=2-(2'-pyridyl)benzimidazole) has been
      synthesized and characterized. The DNA interaction of the complex was studied by
      spectroscopic methods, viscosity, and electrophoresis measurements. The
      antioxidant activity was also investigated using the pyrogallol autoxidation
      assay. Besides, the interaction of the complex with human serum albumin (HSA) in
      vitro was examined by multispectroscopic techniques. The complex partially
      intercalated to CT-DNA with a high binding constant (Kb=7.28*10(5) M(-1)), and
      cleaved pBR322 DNA efficiently via an oxidative mechanism in the presence of Vc,
      with the HO. and O2(-) as the active species, and the SOD as a promoter.
      Furthermore, the complex shows a considerable SOD-like activity with the IC50
      value of 3.8386 MUM. The complex exhibits desired binding affinity to HSA, in
      which hydrogen bond or vander Waals force played a major role. The alterations of
      HSA secondary structure induced by the complex were confirmed by UV-visible, CD,
      synchronous fluorescence and 3D fluorescence spectroscopy.

PMID- 24291452
TI  - Safety of dietary conjugated alpha-linolenic acid (CLNA) in a neonatal pig model.
AB  - The aim of the present study was to perform a short-term safety evaluation of
      dietary mono-conjugated alpha-linolenic acid isomers (CLNA; c9-t11-c15-18:3+c9
      t13-c15-18:3) using a neonatal pig model. CLNA diet was compared with three other
      dietary fats: (1) conjugated linoleic acid (CLA; c9-t11-18:2+t10-c12-18:2), (2)
      non-conjugated n-3 PUFA and (3) n-6 PUFA. Thirty-two piglets weaned at 3 weeks of
      age were distributed into four dietary groups. Diets were isoenergetic and food
      intake was controlled by a gastric tube. Mono-CLNA diet did not significantly
      change body or organ weight, carcass composition and most biochemical parameters
      including; glucose, cholesterol, triglycerides, creatinine, blood urea nitrogen,
      hepatic enzymes and electrolytes levels in blood (P?0.09). Conversely, the n-3
      PUFA composition of the brain, liver and heart decreased by 6-21% in the CLNA-fed
      group compared to animals fed nonconjugated n-3 PUFA (P<0.01). Responses to
      dietary treatments were tissue-specific, with the liver and the brain being the
      most deprived in n-3 PUFA. Our results support that short-term intake of mono
      CLNA is safe in neonatal pigs but n-3 PUFA reduction in tissues deserves to be
      further investigated before using long-term nutritional supplementation in pigs
      and other animal models and before moving to clinical trials.

PMID- 24291453
TI  - Cytotoxic effects of procyanidins from Castanea mollissima Bl. shell on human
      hepatoma G2 cells in vitro.
AB  - Significant cytotoxic effects of procynadins from chestnut (Castanea mollissima
      Bl.) shell (CSPC) on human hepatoma G2 (HepG2) cells were found in vitro. CSPC
      could inbibit HepG2 proliferation in a dose-dependent manner (100-400 MUg/mL),
      arrest cell cycle in the G0/G1 phase, induce apoptosis and trigger necrosis of
      HepG2. Proapoptotic effect of CSPC was evidenced by nuclear condensation,
      internucleosomal DNA fragmentation. Treatment of HepG2 cells with CSPC caused a
      loss of mitochondrial membrane potential and stimulated reactive oxidative
      species (ROS) generation. These results suggested CSPC could trigger apoptosis
      and necrotic cell death in HepG2 cell, which might be associated with ROS
      generation through the mitochondria-dependent signaling way.

PMID- 24291454
TI  - Some considerations concerning the theory of combined toxicity: a case study of
      subchronic experimental intoxication with cadmium and lead.
AB  - Rats were exposed intraperitoneally (3 times a week up to 20 injections) to
      either Cadmium and Lead salts in doses equivalent to their 0.05 LD50 separately
      or combined in the same or halved doses. Toxic effects were assessed by more than
      40 functional, biochemical and morphometric indices. We analysed the results
      obtained aiming at determination of the type of combined toxicity using either
      common sense considerations based on descriptive statistics or two mathematical
      models based (a) on ANOVA and (b) on Mathematical Theory of Experimental Design,
      which correspond, respectively, to the widely recognised paradigms of effect
      additivity and dose additivity. Nevertheless, these approaches have led us
      unanimously to the following conclusions: (1) The above paradigms are virtually
      interchangeable and should be regarded as different methods of modelling the
      combined toxicity rather than as reflecting fundamentally differing processes.
      (2) Within both models there exist not merely three traditionally used types of
      combined toxicity (additivity, subadditivity and superadditivity) but at least 10
      variants of it depending on exactly which effect is considered and on its level,
      as well as on the dose levels and their ratio.

PMID- 24291455
TI  - The PICTURE study -- prostate imaging (multi-parametric MRI and Prostate
      HistoScanningTM) compared to transperineal ultrasound guided biopsy for
      significant prostate cancer risk evaluation.
AB  - OBJECTIVE: The primary objective of the PICTURE study is to assess the negative
      predictive value of multi-parametric MRI (mp-MRI) and Prostate HistoScanningTM
      (PHS) in ruling-out clinically significant prostate cancer. PATIENTS AND METHODS:
      PICTURE is a prospective diagnostic validating cohort study conforming to level 1
      evidence. PICTURE will assess the diagnostic performance of multi-parametric
      Magnetic Resonance Imaging (mp-MRI) and Prostate HistoScanningTM (PHS)
      ultrasound. PICTURE will involve validating both index tests against a reference
      test, transperineal Template Prostate Mapping (TPM) biopsies, which can be
      applied in all men under evaluation. Men will be blinded to the index test
      results and both index tests will be reported prospectively prior to the biopsies
      being taken to ensure reporter blinding. Paired analysis of each of the index
      tests to the reference test will be done at patient level. Those men with an
      imaging lesion will undergo targeted biopsies to assess the clinical utility of
      sampling only suspicious areas. The study is powered to assess the negative
      predictive value of these imaging modalities in ruling-out clinically significant
      prostate cancer. DISCUSSION: The PICTURE study aims to assess the performance
      characteristics of two imaging modalities (mp-MRI and Prostate HistoScanning) for
      their utility in the prostate cancer pathway. PICTURE aims to identify if either
      imaging test may be useful for ruling out clinically significant disease in men
      under investigation, and also to examine if either imaging modality is useful for
      the detection of disease. Recruitment is underway and expected to complete in
      2014.

PMID- 24291456
TI  - Exercise for methamphetamine dependence: rationale, design, and methodology.
AB  - BACKGROUND: Effective pharmacotherapies to treat methamphetamine (MA) dependence
      have not been identified, and behavioral therapies are marginally effective.
      Based on behavioral studies demonstrating the potential efficacy of aerobic
      exercise for improving depressive symptoms, anxiety, cognitive deficits, and
      substance use outcomes, the study described here is examining exercise as a
      potential treatment for MA-dependent individuals. METHODS: This study is
      randomizing 150 participants with MA dependence at a residential treatment
      facility for addictive disorders to receive either a thrice-weekly structured
      aerobic and resistance exercise intervention or a health education condition.
      Recruitment commenced in March, 2010. Enrollment and follow-up phases are
      ongoing, and recruitment is exceeding targeted enrollment rates. CONCLUSIONS:
      Seeking evidence for a possibly effective adjunct to traditional behavioral
      approaches for treatment of MA dependence, this study is assessing the ability of
      an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use
      during a 12-week follow-up period after discharge from residential-based
      treatment. The study also is evaluating improvements in health and functional
      outcomes during and after the protocol. This paper describes the design and
      methods of the study.

PMID- 24291458
TI  - Extracellular matrix proteins: a positive feedback loop in lung fibrosis?
AB  - Lung fibrosis is characterized by excessive deposition of extracellular matrix.
      This not only affects tissue architecture and function, but it also influences
      fibroblast behavior and thus disease progression. Here we describe the expression
      of elastin, type V collagen and tenascin C during the development of bleomycin
      induced lung fibrosis. We further report in vitro experiments clarifying both the
      effect of myofibroblast differentiation on this expression and the effect of
      extracellular elastin on myofibroblast differentiation. Lung fibrosis was induced
      in female C57Bl/6 mice by bleomycin instillation. Animals were sacrificed at zero
      to five weeks after fibrosis induction. Collagen synthesized during the week
      prior to sacrifice was labeled with deuterium. After sacrifice, lung tissue was
      collected for determination of new collagen formation, microarray analysis, and
      histology. Human lung fibroblasts were grown on tissue culture plastic or BioFlex
      culture plates coated with type I collagen or elastin, and stimulated to undergo
      myofibroblast differentiation by 0-10 ng/ml transforming growth factor
      (TGF)beta1. mRNA expression was analyzed by quantitative real-time PCR. New
      collagen formation during bleomycin-induced fibrosis was highly correlated to
      gene expression of elastin, type V collagen and tenascin C. At the protein level,
      elastin, type V collagen and tenascin C were highly expressed in fibrotic areas
      as seen in histological sections of the lung. Type V collagen and tenascin C were
      transiently increased. Human lung fibroblasts stimulated with TGFbeta1 strongly
      increased gene expression of elastin, type V collagen and tenascin C. The
      extracellular presence of elastin increased gene expression of the
      myofibroblastic markers alpha smooth muscle actin and type I collagen. The
      extracellular matrix composition changes dramatically during the development of
      lung fibrosis. The increased levels of elastin, type V collagen and tenascin C
      are probably the result of increased expression by fibroblastic cells; reversely,
      elastin influences myofibroblast differentiation. This suggests a reciprocal
      interaction between fibroblasts and the extracellular matrix composition that
      could enhance the development of lung fibrosis.

PMID- 24291457
TI  - Characterization of elements involved in allosteric light regulation of
      phosphodiesterase activity by comparison of different functional BlrP1 states.
AB  - Bacteria have evolved dedicated signaling mechanisms that enable the integration
      of a range of environmental stimuli and the accordant modulation of metabolic
      pathways. One central signaling molecule in bacteria is the second messenger
      cyclic dimeric GMP (c-di-GMP). Complex regulatory mechanisms for modulating c-di
      GMP concentrations have evolved, in line with its importance for maintaining
      bacterial fitness under changing environmental conditions. One interesting
      example in this context is the blue-light-regulated phosphodiesterase 1 (BlrP1)
      of Klebsiella pneumoniae. This covalently linked system of a sensor of blue light
      using FAD (BLUF) and an EAL phosphodiesterase domain orchestrates the light
      dependent down-regulation of c-di-GMP levels. To reveal details of light-induced
      structural changes involved in EAL activity regulation, we extended previous
      crystallographic studies with hydrogen-deuterium exchange experiments and small
      angle X-ray scattering analysis of different functional BlrP1 states. The
      combination of hydrogen-deuterium exchange and small-angle X-ray scattering
      allows the integration of local and global structural changes and provides an
      improved understanding of light signaling via an allosteric communication pathway
      between the BLUF and EAL domains. This model is supported by results from a
      mutational analysis of the EAL dimerization region and the analysis of metal
      coordination effects of the EAL active site on the dark-state recovery kinetics
      of the BLUF domain. In combination with structural information from other EAL
      domains, the observed bidirectional communication points to a general mechanism
      of EAL activity regulation and suggests that a similar allosteric coupling is
      maintained in catalytically inactive EAL domains that retain a regulatory
      function. 

PMID- 24291459
TI  - Three bioactive cyclic dipeptides from the Bacillus sp. N strain associated with
      entomopathogenic nematode.
AB  - In continuation of our search for new bioactive secondary metabolites from
      Bacillus cereus associated with entomopathogenic nematode (EPN), three cyclic
      dipeptides (CDPs), cyclo(L-Leu-D-Arg) (1), cyclo(2-hydroxy-Pro-L-Leu) (2), and
      cyclo(L-Val-L-Pro) (3) were purified from the ethyl acetate extract of B. cereus.
      The chemical structure of the compounds was identified by 1D, 2D NMR and HR-ESI
      MS. Cyclo(L-Leu-D-Arg) recorded best antifungal activity and the highest activity
      was recorded against Cryptococcus neoformans (1 MUg/mL), which is better than the
      standard antifungal agent amphotericin B. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assay was used for finding cell proliferation
      inhibition and cyclo(L-Leu-D-Arg) recorded significant activity against breast
      cancer cell line (MDAM-B231) (IC50 value: 25 MUM) and the three cyclic dipeptides
      recorded no toxicity against normal human cell (fore skin (FS) normal fibroblast)
      up to 50 MUM except cyclo(L-Val-L-Pro). Cyclo(L-Leu-D-Arg) induced significant
      morphological changes and DNA fragmentation associated with apoptosis in MDAM
      B231 cells by acridine orange/ethidium bromide staining and flow cytometry
      analysis. Out of three cyclic dipeptides tested only cyclo(2-hydroxy-Pro-L-Leu)
      recorded significant antioxidant activity. The hydroxyl radical scavenging
      activity of cyclo(2-hydroxy-Pro-L-Leu) is greater than BHA, the standard
      antioxidant agent. Cyclo(L-Leu-D-Arg) was isolated for the first time from a
      natural source with a d-arginine residue. To the best of our knowledge, this is
      the first time that the bioactivity of the isolated cyclic dipeptides is reported
      against medically important fungi and cancer cells. This study is a significant
      contribution to the knowledge of cyclo(L-Leu-D-Arg) from B. cereus as potential
      sources of new drugs in the pharmacological industry, especially as potent
      antifungal and anticancer agent.

PMID- 24291460
TI  - Effect of three larval diets on larval development and male sexual performance of
      Anopheles gambiae s.s.
AB  - Population replacement/elimination strategies based on mass-release of sterile or
      otherwise genetically modified (male) mosquitoes are being considered in order to
      expand the malaria vector control arsenal on the way to eradication. A challenge
      in this context, is to produce male mosquitoes that will be able to compete and
      mate with wild females more efficiently than their wild counterparts, i.e. high
      fitness males. This study explored the effect of three larval food diets
      developed by the International Atomic Energy Agency on the overall fitness and
      mating performance of male Anopheles gambiae s.s. mosquitoes (Kisumu strain).
      Larval development (pupation and emergence rate, development time) was monitored,
      and adult wing length and energy reserves at emergence (i.e. lipids, sugars,
      glycogen and proteins) were measured. Male sexual performance was assessed
      through an insemination test whereby one male and 10 virgin females were
      maintained together in the same cage in order to record the number of inseminated
      females per 24h. Our results show that males reared on Diets 2 and 3 performed
      best during larval development. Males provided with treatment 2.2 had a shorter
      development time and performed best in insemination tests. However, these males
      had the lowest overall lifespan, suggesting a trade-off between longevity and
      sexual performances which needs to be taken into consideration when planning
      release. The results from this work were discussed in the context of sterile
      insect techniques or genetic control methods which is today one of the strategy
      in the overall mosquito control and elimination efforts.

PMID- 24291461
TI  - Swarming and mating behavior of male Anopheles arabiensis Patton (Diptera:
      Culicidae) in an area of the Sterile Insect Technique Project in Dongola,
      northern Sudan.
AB  - The problems facing the conventional mosquito control methods including
      resistance to insecticides have led to the development of alternative methods
      such as the Sterile Insect Technique (SIT) to suppress populations of the malaria
      vector Anopheles arabiensis in northern Sudan. This method entails the release of
      large numbers of irradiated males to compete against wild conspecifics for mating
      with virgin females in the field. The swarming and mating behaviors of this
      species were conducted at two field sites during the period 2009-2012 in Dongola,
      northern Sudan. Observations were made in the field sites and in a contained semi
      field enclosure. In addition, participation of released irradiated-marked males
      in the swarms of wild mosquito was investigated. Swarms were observed on sunset
      in the vicinity of larval habitats around irrigation channel and stopped with the
      onset of the darkness about 21-25 min after the start. Swarms were observed above
      visual markers such as palm trees, bare ground, and manure. Several couples were
      observed leaving the swarms in copula in the direction of the sunlight. The
      majority of copulations were observed within 12-15 min of the start of swarming.
      Relatively low insemination rates (28%) of females collected from coupling pairs
      were observed. Irradiated-marked males were observed to join the natural swarms
      regularly, indicating their probable competitiveness with the other wild males.
      These findings enhance the feasibility of staging an SIT campaign against malaria
      vector in Northern State-Sudan.

PMID- 24291462
TI  - Disarray of glomerular and tubular cell adhesion molecules in the course of
      experimental Bothrops moojeni envenomation.
AB  - In this study, we show that administration of Bothrops moojeni venom in rats
      induces a general disturbance in the distribution and content of the tight
      junctional protein ZO-1, the cell-matrix receptor beta 1 integrin, the
      cytoskeletal proteins, vinculin and F-actin, and of the extracellular matrix
      component laminin in renal corpuscles and cortical nephron tubules. These
      findings suggest that cell-cell and cell-matrix adhesion proteins may be
      molecular targets in the B. moojeni-induced kidney injury. 

PMID- 24291463
TI  - Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic
      pulsatile L-Dopa treatment induced cognitive and emotional alterations.
AB  - L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly
      occurs in elderly patients. However, the effects of chronic use on mood and
      cognition in old subjects remain elusive. In order to compare the effects of a
      chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young
      (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was
      administered every 12 h over 4 weeks. Rats were assessed for behavioural despair
      (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT)
      and spatial learning (Morris water maze, MWM) in the late phase of treatment (T).
      Neuronal expression of Fos in the hippocampus at the early and late phases of T,
      as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and
      D2r receptors were also evaluated in the hippocampus using immunohistochemistry
      and confocal microscopy. Young rats showed similar patterns during behavioural
      tests, whereas aged treated rats showed increased immobility counts in RFST,
      diminished sucrose liquid intake in SPT, and spatial learning impairment during
      MWM. Fos expression was significantly blunted in the aged treated group after
      MWM. The density of D5r, D3r and D2r was increased in both aged groups. The
      treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged
      treated subjects had significant lower values of D5r/D3r and higher values of
      D5r/D2r when compared with young treated subjects. These results indicate that
      chronic L-Dopa treatment in itself could trigger emotional and cognitive
      dysfunctions in elderly subjects through dopamine receptor dysregulation.

PMID- 24291464
TI  - Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor
      protein cleavage.
AB  - Amyloid precursor protein (APP) shedding yields the Alzheimer's disease (AD)
      related peptide amyloid beta (Abeta) through beta- and gamma-secretase cleavage.
      Alternatively, alpha-secretase cleavage generates a soluble and neuroprotective
      fragment (sAPPalpha) while precludes the production of Abeta. Although
      metabotropic glutamate (mGlu) receptors were associated with induction of
      sAPPalpha production in astrocytes, there was no further evidence regarding the
      specific subtype receptor or the mechanisms involved in this action. In the
      present study, we used the dual mGlu2/3 receptor agonist LY379268, which in pure
      astrocyte cultures selectively activates mGlu3 receptor subtype since mGlu2
      receptor subtype is not expressed by these cells. We showed that LY379268
      incremented sAPPalpha release from cultured astrocytes by inducing alpha
      secretases expression, whereas it decreased beta-secretase levels. LY379268
      induced increase of PPAR-gamma levels could be involved in the effect of the
      agonist on sAPPalpha release. Using the PDAPP-J20 murine model of AD we described
      a strong reduction in mGlu2/3 receptor expression in the hippocampus of 5- and 14
      month-old transgenic mice compared to control littermates. Moreover, mGlu3
      receptor expression is also decreased specifically in hippocampal astrocytes of
      these transgenic animals as a function of age. Therefore, diminished levels of
      hippocampal mGlu3 receptors might have implications in the development of the
      disease in these transgenic mice considering the anti-amyloidogenic action of
      mGlu3 receptors in astrocytes. 

PMID- 24291465
TI  - Chemotherapy-induced long-term alteration of executive functions and hippocampal
      cell proliferation: role of glucose as adjuvant.
AB  - In patients, cancer and treatments provoke cognitive impairments referred to
      "chemofog". Here a validated neurobehavioral animal model, the unique way to
      explore causal direct links between chemotherapy used in clinical practices and
      brain disorders, allowed investigation of the direct long-term impact of colo
      rectal cancer chemotherapy on cognition and cerebral plasticity. Young and aged
      mice received three injections every 7 days during 2 weeks of 5-fluorouracil
      either alone (5-FU, 37.5 mg/kg) or in combination with oxaliplatin (3 mg/kg) or
      with glucose (5%). The long-term effects (from day 24 to day 60) of chemotherapy
      were tested on emotional reactivity, learning and memory, behavioral flexibility
      and hippocampal cell plasticity. 5-FU (in saline)-treated aged and also young
      mice exhibited specific altered cognitive flexibility and behavioral hyper
      reactivity to novelty, whereas the combination 5-FU (in saline)/oxaliplatin (in
      glucose) did not provoke any cognitive dysfunction. We thus observed that glucose
      counteracted 5-FU-induced altered executive functions and hippocampal cell
      proliferation in vivo, and protected neural stem cells in vitro from toxicity of
      5-FU or oxaliplatin. In conclusion, these data suggest that the lasting
      chemotherapy-induced selective impairment of executive functions, whatever the
      age, and associated with a reduced number of hippocampal proliferating cells, can
      be counteracted by co-administration with glucose. 

PMID- 24291466
TI  - Selegiline normalizes, while l-DOPA sustains the increased number of dopamine
      neurons in the olfactory bulb in a 6-OHDA mouse model of Parkinson's disease.
AB  - Olfactory dysfunction, often preceding the cardinal motor symptoms, such as
      bradykinesia, rigidity, tremor at rest and postural instability, is frequently
      reported in Parkinson's disease. This symptom appears to be related to an
      increased number of dopamine neurons in the periglomerular layer of the olfactory
      bulb. In animal models of Parkinson's disease, adult neural progenitor cells
      migrating from the subventricular zone of the lateral ventricle to the olfactory
      bulb are evidently altered in their survival and progeny. The modulation of
      neural progenitor cells contributing to the number of dopamine neurons in the
      periglomerular layer, however, is still poorly understood. In this study, we have
      investigated the survival and neuronal differentiation of newly generated cells
      in the olfactory bulb, following treatment with the dopamine precursor l-DOPA and
      the monoamine oxidase-B inhibitor selegiline in a unilateral, intranigral 6
      hydroxydopamine lesion model in mice. Our data show that the number of neural
      progenitor cells in the subventricular zone is decreased after an intranigral 6
      hydroxydopamine lesion, while there is no difference from control in lesioned
      mice with selegiline or l-DOPA treatment. Selegiline is able to normalize the
      number of dopamine neurons in the periglomerular layer, while l-DOPA treatment
      sustains the increased number observed in 6-hydroxydopamine lesioned animals. We
      conclude that there is a distinct modulation of newly generated dopamine neurons
      of the olfactory bulb after l-DOPA and selegiline treatment. The differential
      effects of the two drugs might also play a role in olfactory dysfunction in
      Parkinson's disease patients. 

PMID- 24291468
TI  - Proteomics-based identification of plasma proteins and their association with the
      host-pathogen interaction in chronic typhoid carriers.
AB  - BACKGROUND: Current diagnostic tests are inadequate to detect typhoid cases, as
      well as the chronic carrier state, the sole reservoir of Salmonella enterica
      serovar Typhi. The current study was conducted to find new molecular signatures
      of pathogen/disease to understand the mechanism behind the host-pathogen
      interaction in enteric fever. METHODS: Proteomics-based studies were done to
      determine the expression of differentially expressed proteins in the plasma of
      controls, acute typhoid cases, and chronic typhoid carriers. Further,
      transcriptome-based analysis using reverse-transcriptase PCR (RT-PCR) was done in
      controls, acute typhoid cases, and chronic typhoid carriers. RESULTS: Results
      showed the upregulation of proprotein convertase subtilisin, furin, haptoglobin,
      and albumin in the plasma of chronic typhoid carriers. The elevation in mRNA
      expression of four differentially expressed proteins confirms the changes at the
      transcriptional level. Further, the increase in albumin and haptoglobin in
      chronic typhoid carriers shows their role in free radical generation,
      inflammation, and monocyte cell signaling. CONCLUSION: Through proteomics
      techniques, this study identified four proteins in the chronic typhoid carrier
      host that may have a role in the disease pathogenesis of enteric fever.

PMID- 24291467
TI  - Pacemaker-related infection detected by (18)F-fluorodeoxyglucose positron
      emission tomography-computed tomography.
AB  - Lead endocarditis (LE) is one of the most feared complications and remains a
      challenging diagnosis in cardiology due to the possibility of an obscure clinical
      course and symptoms, leading to a delayed diagnosis, or even no diagnosis. (18)F
      fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT)
      appears to be a valuable imaging technique and has been shown to have advantages
      in the diagnosis of patients with fever of unknown origin. We present the case of
      a 52-year-old man with a 3-year history of intermittent fever, chills, anemia,
      and weight loss (13kg). He was submitted to an extensive investigation to clarify
      his symptoms and all results were negative. LE was finally diagnosed by FDG
      PET/CT. This examination could become a useful noninvasive method for the
      detection of LE at an earlier stage, thus avoiding repeated tests and reducing
      the length of hospital stay. 

PMID- 24291469
TI  - In vitro toxicity testing with microplate cell cultures: Impact of cell binding.
AB  - In vitro generated data on toxic potencies are generally based on nominal
      concentrations. However, cellular and extracellular binding and elimination
      processes may reduce the available free fraction of a compound. Then, nominal
      effective concentrations do not represent appropriate measures of toxic exposure
      in vitro and underestimate toxic potencies. In this study it was investigated
      whether cell binding can affect the availability of chemicals in microplate based
      toxicity assays. To this end the cytotoxicity of compounds like mercury chloride,
      digitonin and alcohol ethoxylates, accumulated by cells via different modes, was
      investigated in 96-well microplate cultures with varying concentrations of Balb/c
      3T3 cells. The median effective nominal concentrations of all but one of the
      tested compounds depended linearly from the cell concentration. Applying a
      previously developed equilibrium distribution model cell concentration
      independent median effective extracellular concentrations and cell burdens,
      respectively, could be calculated. The compounds were accumulated by the cells
      with bioconcentration factors, BCF, between 480 and >= 25,000. Cell binding of
      the alcohol ethoxylates was correlated with their lipophilicity. The results show
      that significant cell binding can occur even at the small cell volume fractions
      (~ 1 * 10(-5) to 3 * 10(-3) L/L) encountered in microplate assays. To what extent
      cell binding affects the bioavailability depends on the BCF and the cell volume
      fraction. EC50 measurements in the presence of at least two different cell
      concentrations allow for excluding or detecting significant cell binding and for
      determining more appropriate measures of toxic exposure in vitro like median
      effective extracellular (free) concentrations or cell burdens.

PMID- 24291470
TI  - A weakened mechanism is still a mechanism: on the causal role of absences in
      mechanistic explanation.
AB  - Much contemporary debate on the nature of mechanisms centers on the issue of
      modulating negative causes. One type of negative causability, which I refer to as
      "causation by absence," appears difficult to incorporate into modern accounts of
      mechanistic explanation. This paper argues that a recent attempt to resolve this
      problem, proposed by Benjamin Barros, requires improvement as it overlooks the
      fact that not all absences qualify as sources of mechanism failure. I suggest
      that there are a number of additional types of effects caused by absences that
      need to be incorporated to account for the diversity of causal connections in the
      biological sciences. Furthermore, it is argued that recognizing natural
      variability in mechanisms, such as attenuation, leads to some interesting line
      drawing issues for contemporary philosophy of mechanisms. 

PMID- 24291471
TI  - The incidence of idiopathic musculoskeletal pain in children with upper extremity
      injuries.
AB  - INTRODUCTION: Children with upper extremity injuries may report persistent pain
      beyond the period of acute injury. In the published literature, it is unclear
      whether these children develop idiopathic musculoskeletal pain (IMP) such as
      complex regional pain syndrome (CRPS). The purpose of this study was to determine
      the incidence rate of IMP after upper extremity injury in school-aged children
      over a 5-year period and to describe the characteristics of these children.
      METHODS: A retrospective case series was conducted of all children aged 8-18
      years with an upper extremity injury who attended the outpatient hand clinic in a
      tertiary care pediatric hospital. RESULTS: A reported incidence rate of IMP was
      1.9% over a 5-year period in the 879 children reviewed. Girls were more likely to
      have IMP. The categorical distribution of the type, etiology and anatomical
      location of injury was proportionately different for those with IMP compared to
      those without documentation of IMP. In comparison, a higher percentage of
      children with IMP reported disproportionate pain and hypersensitivity or
      neuropathic pain symptoms compared to the children who had pain from a known
      etiology. CONCLUSION: The incidence rate of IMP after upper extremity injury in
      school-aged children is low. Some common characteristics of this population that
      may help clinicians identify these children and make timely referrals for
      treatment include female gender, disproportionate pain, previously seen by
      multiple specialists, generalized injury in the hand, unspecific etiology or type
      of injury and unremarkable x-rays.

PMID- 24291472
TI  - Biogenic and synthetic high magnesium calcite - a review.
AB  - Systematic studies on the Mg distributions, the crystal orientations, the
      formation mechanisms and the mechanical properties of biogenic high-Mg calcites
      in different marine organisms were summarized in detail in this review. The high
      Mg calcites in the hard tissues of marine organisms mentioned generally own a few
      common features as follows. Firstly, the Mg distribution is not uniform in most
      of the minerals. Secondly, high-Mg calcite biominerals are usually composed of
      nanoparticles that own almost the same crystallographic orientations and thus
      they behave like single crystals or mesocrystals. Thirdly, the formation of
      thermodynamically unstable high-Mg calcites in marine organisms under mild
      conditions is affected by three key factors, that is, the formation of amorphous
      calcium (magnesium) carbonate precursor, the control of polymorph via
      biomolecules and the high Mg/Ca ratios in modern sea. Lastly, the existence of Mg
      ions in the Mg-containing calcite may improve the mechanical properties of
      biogenic minerals. Furthermore, the key progress in the synthesis of high-Mg
      calcites in the laboratory based on the formation mechanisms of the biogenic high
      Mg calcites was reviewed. Many researchers have realized the synthesis of high-Mg
      calcites in the laboratory under ambient conditions with the help of intermediate
      amorphous phase, mixed solvents, organic/inorganic surfaces and soluble
      additives. Studies on the structural analysis and formation mechanisms of
      thermodynamically unstable biogenic high-Mg calcite minerals may shed light on
      the preparation of functional materials with enhanced mechanical properties. 

PMID- 24291473
TI  - Acute pancreatitis and elevated liver transaminases after rapid titration of oral
      levetiracetam.
AB  - We report a 25-year-old woman with new onset convulsive episodes. The patient
      initially failed to respond to phenytoin and was switched to levetiracetam (LEV)
      which was rapidly titrated to 3000 mg daily over 1 week. At initiation of LEV
      therapy, she developed mild nausea and decrease in appetite. This was rapidly
      followed by severe digestive symptoms consistent with acute pancreatitis. She was
      also found to have elevated liver transaminases. An extensive work-up failed to
      reveal an organic cause for her symptoms, suggesting a direct relationship to
      LEV. Clinical symptoms and laboratory abnormalities normalized after LEV
      discontinuation, along with supportive therapy.

PMID- 24291474
TI  - Arachnoiditis ossificans of the thoracic spine.
AB  - Arachnoiditis ossificans is a rare disorder characterized by the development of
      calcifications of the arachnoid membrane of the thoracic and lumbar spines. It is
      an extremely rare cause of spinal canal stenosis and consequent neurological
      compromise, and its origins and optimal management remain unclear. We review of
      the literature that illustrates the challenges of diagnosis and treatment of
      arachnoiditis ossificans. A patient with arachnoiditis ossificans is discussed to
      illustrate the presentation, treatment, and prognosis of the disease. 

PMID- 24291475
TI  - Intraneural fibroma of the median nerve at the wrist.
AB  - Distal median neuropathy from carpal tunnel syndrome is the most well known
      lesion affecting the median nerve. Mass lesions may affect the nerve at the
      wrist. We present to our knowledge the first histologically confirmed case of an
      intraneural fibroma. 

PMID- 24291476
TI  - Temozolomide-related acute lymphoblastic leukemia with translocation
      (4;11)(q21;q23) in a glioblastoma patient.
AB  - Temozolomide (TMZ), an alkylating agent, is widely used for treating high-grade
      gliomas. TMZ has been reported to cause secondary myelodysplastic syndrome and
      acute myeloid leukemia. However, TMZ-related acute lymphoblastic leukemia is
      rare. Here we describe a 54-year-old woman with glioblastoma multiforme, who
      developed precursor-B acute lymphoblastic leukemia with translocation
      (4;11)(q21;q23) after 15 months of TMZ treatment.

PMID- 24291477
TI  - Risk factors for dural arteriovenous fistula intracranial hemorrhage.
AB  - To our knowledge, the risk factors for intracranial hemorrhage from dural
      arteriovenous fistula (DAVF) have not been systematically described, due to the
      complexity of their anatomy and low incidence. We performed this retrospective
      study to investigate the DAVF factors predicting intracranial hemorrhage. A
      10year database of 144 consecutive patients with DAVF was reviewed. Data
      collected and analyzed were demographics, morphologic features of DAVF, sex, age,
      fistula flow rate, arterial supply, lesion location, and venous drainage pattern.
      Linear univariate and multivariate logistic regression analyses were used to
      evaluate the association between influencing factors and hemorrhage. A first
      linear univariate analysis was performed for all influencing factors, and showed
      that sex, lesion location, and venous drainage pattern were statistically
      significant in predicting intracranial hemorrhage (p<0.05). Secondary
      multivariate logistic regression analysis with sex, lesion location, and venous
      drainage pattern showed that only venous drainage pattern was statistically
      significant in predicting intracranial hemorrhage (p<0.05). Therefore, venous
      drainage pattern, particularly the cortical venous drainage, significantly
      predicts intracranial hemorrhage from DAVF. Both sex and lesion location may be
      confounding factors in predicting intracranial hemorrhage from DAVF, while the
      other factors may not be associated with hemorrhage.

PMID- 24291478
TI  - High-frequency stimulation of the globus pallidus interna nucleus modulates
      GFRalpha1 gene expression in the basal ganglia.
AB  - Deep brain stimulation (DBS) is an established therapy for movement disorders
      such as Parkinson's disease (PD). Although the efficacy of DBS is clear, its
      precise molecular mechanism remains unknown. The glial cell line derived factor
      (GDNF) family of ligands has been shown to confer neuroprotective effects on
      dopaminergic neurons, and putaminal infusion of GDNF have been investigated in PD
      patients with promising results. Despite the potential therapeutic role of GDNF
      in alleviating motor symptoms, there is no data on the effects of electrical
      stimulation on GDNF-family receptor (GFR) expression in the basal ganglia
      structures. Here, we report the effects of electrical stimulation on GFRalpha1
      isoforms, particularly GFRalpha1a and GFRalpha1b. Wistar rats underwent 2 hours
      of high frequency stimulation (HFS) at the globus pallidus interna nucleus. A
      control group was subjected to a similar procedure but without stimulation. The
      HFS group, sacrificed 24 hours after treatment, had a threefold decrease in mRNA
      expression level of GFRalpha1b (p=0.037), but the expression level reverted to
      normal 72 hours after stimulation. Our preliminary data reveal the acute effects
      of HFS on splice isoforms of GFRalpha1, and suggest that HFS may modulate the
      splice isoforms of GFRalpha1a and GFRalpha1b to varying degrees. Going forward,
      elucidating the interactions between HFS and GFR may shed new insights into the
      complexity of GDNF signaling in the nervous system and lead to better design of
      clinical trials using these signaling pathways to halt disease progression in PD
      and other neurodegenerative diseases.

PMID- 24291479
TI  - Paradoxical migrating cyst: an unusual presentation of intraventricular
      neurocysticercosis with a coincidental pituitary adenoma.
AB  - Intraventricular neurocysticercosis is an uncommon entity which may become
      symptomatic due to cerebrospinal fluid flow obstruction. Migration of
      intraventricular cysts through the ventricular spaces is a rare occurrence. This
      phenomenon is poorly understood but may be due to pressure changes within the
      ventricular cavities. We present a patient with intraventricular
      neurocysticercosis with paradoxical transaqueductal migration of the cyst from
      the cerebral aqueduct to the fourth ventricle shortly after ventricular drain
      placement for acute hydrocephalus. The patient also presented with a coincidental
      sellar and suprasellar mass, later pathologically proven to be a pituitary
      adenoma. The migration of this cyst resulted in spontaneous relief of obstruction
      at the cerebral aqueduct, thus restoring normal cerebrospinal fluid pathways and
      avoiding permanent shunting. We discuss the possible mechanisms and implications
      of cyst migration, and the diagnostic challenges of concomitant findings of a
      pituitary mass and neurocysticercosis. Although the presence of a sellar and
      suprasellar mass in a patient with known neurocysticercosis should raise clinical
      suspicion for the possibility of sellar neurocysticercosis, pituitary
      macroadenoma is a more common entity and a more likely etiology for a sellar
      lesion. 

PMID- 24291480
TI  - X-microstenting and transmesh coiling in the management of wide-necked tent-like
      anterior communicating artery aneurysms.
AB  - Anterior communicating artery (AcomA) aneurysms frequently have wide necks and an
      irregular shape, incorporate parent vessels, and are associated with significant
      variations in vascular anatomy. Safe and complete endovascular occlusion of these
      aneurysms usually requires the assistance of combined approaches using balloons
      and stents in an individually tailored strategy. We describe a technique for X
      configured stent-assisted coiling in the management of a small tricuspid tent
      like wide-necked AcomA aneurysm by means of two crossed nitinol self-expandable
      Leo+ Baby stents (Balt Therapeutics, Montmorency, France) followed by "in stent"
      transmesh coiling. The addition of a low-profile stent into the
      neurointerventional armamentarium will substantially enhance our capability to
      treat previously uncoilable tent-like AcomA aneurysms. 

PMID- 24291481
TI  - Toxic leukoencephalopathy with atypical MRI features following a lacquer thinner
      fire.
AB  - Toxic leukoencephalopathy is a structural alteration of the white matter
      following exposure to various toxic agents. We report a 49-year-old man exposed
      to an explosion of lacquer thinner with brain MRI features atypical from those of
      chronic toxic solvent intoxication.

PMID- 24291482
TI  - Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non
      Parkinson's disease parkinsonian syndrome.
AB  - Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is
      a useful treatment in patients with tremor-dominant Parkinson's disease (PD).
      Efficacy to alleviate rigidity remains controversial. We report a 65-year-old
      right-handed man with persistent severe rigidity and bradykinesia on the right
      side despite daily administration of levodopa/carbidopa (600/60mg). His right
      hand tremor was continuous at rest and present at action. His antiparkinsonian
      medications appeared ineffective and he reported difficulties with writing and
      eating. Repeated (123)I-meta-iodobenzylguanidine myocardial scintigraphy studies
      demonstrated a non-PD pattern. He underwent the stereotactic implantation of a
      DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous
      unipolar stimulation with a pulse generator implanted in a subclavian pocket.
      This improved the tremor and the rigidity and bradykinesia of his right hand.
      Postoperative image analysis revealed the likelihood of simultaneous stimulation
      of the Vim and the nucleus ventralis oralis posterior. Our findings suggest
      thalamic stimulation as a therapeutic option for drug-resistant rigidity (and
      tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at
      the globus pallidus internus or subthalamic nucleus.

PMID- 24291484
TI  - Upper limb compartment syndrome: an unusual complication of stroke thrombolysis.
AB  - Bleeding is the most important complication of treatment with intravenous tissue
      plasminogen activator for acute ischemic stroke. Neurologists are familiar with
      intracranial hemorrhage, the most feared site for bleeding following
      thrombolysis, but extracranial bleeding can also occur resulting in substantial
      morbidity and mortality. We describe an 88-year-old woman with an acute stroke
      who developed bleeding into the left arm complicated by hemodynamic instability
      and compartment syndrome following intravenous thrombolysis. The patient was
      treated conservatively in view of the risks associated with fasciotomy and her
      other medical comorbidities.

PMID- 24291483
TI  - The role of the brain-derived neurotrophic factor SNP rs2883187 in the phenotypic
      expression of obsessive-compulsive disorder.
AB  - We investigated the association between a brain-derived neurotrophic factor
      (BDNF) gene polymorphism and clinical features in a sample of patients with
      obsessive-compulsive disorder (OCD). A total of 100 patients diagnosed with OCD
      according to the Diagnostic and Statistical Manual IV criteria and 110 control
      subjects were included in this study. The distribution of a single nucleotide
      polymorphism rs2883187 was compared in OCD patients and normal controls. Clinical
      features were compared between the subgroups of OCD patients with different
      genotypes. There was no significant difference for the allele frequencies and
      genotype distributions between the OCD and control groups. The Hamilton Anxiety
      Rating Scale, Yale-Brown Obsessive Compulsive Scale obsession and total scores
      were found to be higher in patients with the CC genotype than in the patients who
      are homozygous for the T allele. The rates of OCD in first-degree relatives of
      OCD patients who were homozygous for the C allele were significantly higher,
      compared to those with CT and TT genotypes. Our results indicate that the CC
      genotype may be associated with the severity and increased familial loading of
      OCD. Further investigation based on larger populations is needed to reveal the
      full association of the BDNF polymorphism with OCD.

PMID- 24291485
TI  - Effects of vinpocetine and ozagrel on behavioral recovery of rats after global
      brain ischemia.
AB  - Brain ischemia leads to severe disruption of the nervous system and recovery is
      often prolonged. Rehabilitative post-ischemia pharmacological treatment may
      therefore be important for behavioral recovery, especially for cognition and
      motor behavior. The present study investigated the effects of combined
      vinpocetine and ozagrel administration on the behavioral recovery of rats from
      global brain ischemia. The results suggest that the combined treatment leads to
      significantly better improvement compared to single drug administration. We
      conclude that the combined use of vinpocetine and ozagrel may provide beneficial
      effects to patients suffering from brain ischemia. 

PMID- 24291487
TI  - Targeting the Akt1 allosteric site to identify novel scaffolds through virtual
      screening.
AB  - Preclinical data and tumor specimen studies report that AKT kinases are related
      to many human cancers. Therefore, identification and development of small
      molecule inhibitors targeting AKT and its signaling pathway can be therapeutic in
      treatment of cancer. Numerous studies report inhibitors that target the ATP
      binding pocket in the kinase domains, but the similarity of this site, within the
      kinase family makes selectivity a major problem. The sequence identity amongst PH
      domains is significantly lower than that in kinase domains and developing more
      selective inhibitors is possible if PH domain is targeted. This in silico
      screening study is the first time report toward the identification of potential
      allosteric inhibitors expected to bind the cavity between kinase and PH domains
      of Akt1. Structural information of Akt1 was used to develop structure-based
      pharmacophore models comprising hydrophobic, acceptor, donor and ring features.
      The 3D structural information of previously identified allosteric Akt inhibitors
      obtained from literature was employed to develop a ligand-based pharmacophore
      model. Database was generated with drug like subset of ZINC and screening was
      performed based on 3D similarity to the selected pharmacophore hypotheses.
      Binding modes and affinities of the ligands were predicted by Glide software. Top
      scoring hits were further analyzed considering 2D similarity between the
      compounds, interactions with Akt1, fitness to pharmacophore models, ADME,
      druglikeness criteria and Induced-Fit docking. Using virtual screening
      methodologies, derivatives of 3-methyl-xanthine, quinoline-4-carboxamide and 2-[4
      (cyclohexa-1,3-dien-1-yl)-1H-pyrazol-3-yl]phenol were proposed as potential leads
      for allosteric inhibition of Akt1. 

PMID- 24291486
TI  - Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded
      protein response and heme oxygenase-1 expression in PC12 cells: Roles of ROS and
      MAPK pathways.
AB  - This study investigates the roles of ROS overproduction and MAPK signaling
      pathways in the induction of unfolded protein response (UPR) and the expression
      of Phase II enzymes in response to 4-hydroxy-trans-2-nonenal (4-HNE) in a
      neuronal-like catecholaminergic PC12 cells. Our results showed that 4-HNE
      triggered three canonical pathways of UPR, namely IRE1-XBP1, PERK-eIF2alpha-ATF4
      and ATF6, and induced the expression of UPR-targeted genes, GRP78, CHOP, TRB3,
      PUMA, and GADD34, as well as Phase II enzymes, HO-1 and GCLC. 4-HNE also induced
      apoptosis, intracellular calcium accumulation, caspase-3 activation, and G0/G1
      cell cycle arrest, which was correlated with the increased expression of
      GADD45alpha. The addition of tiron, a cellular permeable superoxide scavenger,
      scavenged 4-HNE-mediated ROS formation, but did not alleviate cytotoxicity, or
      the expression of UPR-targeted genes or Phase II enzymes, indicating that ROS
      overproduction per se did not play a major role in 4-HNE-caused deleterious
      effects. HO-1 expression was attenuated by Nrf2 siRNA and chemical chaperone 4
      phenylbutyrate (4-PBA), suggesting HO-1 expression was regulated by Nrf2-ARE,
      which may work downstream of ER stress. 4-HNE treatment promptly induced ERK, JNK
      and p38 MAPK activation. Addition of p38 MAPK specific inhibitor SB203580
      attenuated HO-1 upregulation, but enhanced expression of CHOP, PUMA and TRB3, and
      cytotoxicity. These results indicate that 4-HNE-induced transient p38 MAPK
      activation may serve as an upstream negative regulator of ER stress and confer
      adaptive cytoprotection against 4-HNE-mediated cell injury.

PMID- 24291488
TI  - The optimization of running time for a maximum common substructure-based
      algorithm and its application in drug design.
AB  - In the field of drug discovery, it is particularly important to discover
      bioactive compounds through high-throughput virtual screening. The maximum common
      substructure-based (MCS) algorithm is a promising method for the virtual
      screening of drug candidates. However, in practical applications, there is always
      a trade-off between efficiency and accuracy. In this paper, we optimized this
      method by running time evaluation using essential drugs defined by WHO and FDA
      approved small-molecule drugs. The amount of running time allocated to the MCS
      based virtual screening was varied, and statistical analysis was conducted to
      study the impact of computation running time on the screening results. It was
      determined that the running time efficiency can be improved without compromising
      accuracy by setting proper running time thresholds. In addition, the similarity
      of compound structures and its relevance to biological activity are analyzed
      quantitatively, which highlight the applicability of the MCS-based methods in
      predicting functions of small molecules. 15-30s was established as a reasonable
      range for selecting a candidate running time threshold. The effect of CPU speed
      is considered and the conclusion is generalized. The potential biological
      activity of small molecules with unknown functions can be predicted by the MCS
      based methods. 

PMID- 24291489
TI  - Modeling of tumor growth in dendritic cell-based immunotherapy using artificial
      neural networks.
AB  - Exposure-response modeling and simulation is especially useful in oncology as it
      permits to predict and design un-experimented clinical trials as well as dose
      selection. Dendritic cells (DC) are the most effective immune cells in the
      regulation of immune system. To activate immune system, DCs may be matured by
      many factors like bacterial CpG-DNA, Lipopolysaccharaide (LPS) and other
      microbial products. In this paper, a model based on artificial neural network
      (ANN) is presented for analyzing the dynamics of antitumor vaccines using
      empirical data obtained from the experimentations of different groups of mice
      treated with DCs matured by bacterial CpG-DNA, LPS and whole lysate of a Gram
      positive bacteria Listeria monocytogenes. Also, tumor lysate was added to DCs
      followed by addition of maturation factors. Simulations show that the proposed
      model can interpret the important features of empirical data. Owing to the
      nonlinearity properties, the proposed ANN model has been able not only to
      describe the contradictory empirical results, but also to predict new vaccination
      patterns for controlling the tumor growth. For example, the proposed model
      predicts an exponentially increasing pattern of CpG-matured DC to be effective in
      suppressing the tumor growth. 

PMID- 24291490
TI  - Multiscale modelling to understand the self-assembly mechanism of human beta2
      adrenergic receptor in lipid bilayer.
AB  - The long perceived notion that G-Protein Coupled Receptors (GPCRs) function in
      monomeric form has recently been changed by the description of a number of GPCRs
      that are found in oligomeric states. The mechanism of GPCR oligomerization, and
      its effect on receptor function, is not well understood. In the present study,
      coarse grained molecular dynamics (CGMD) approach was adopted for studying the
      self-assembly process of the human GPCR, beta2-adrenergic receptor (beta2-AR),
      for which several experimental evidences of the dimerization process and its
      effect on cellular functions are available. Since the crystal structure of beta2
      AR lacks the third intracellular loop, initially it was modelled and simulated
      using restrained MD in order to get a stable starting conformation. This
      structure was then converted to CG representation and 16 copies of it, inserted
      into a hydrated lipid bilayer, were simulated for 10 MUs using the MARTINI force
      field. At the end of 10MUs, oligomers of beta2-AR were found to be formed through
      the self-assembly mechanism which were further validated through various analyses
      of the receptors. The lipid bilayer analysis also helped to quantify this
      assembly mechanism. In order to identify the domains which are responsible for
      this oligomerization, a reverse transformation of the CG system back to all-atom
      structure and simulated annealing run were carried out at the end of 10 MUs CGMD
      run. Analysis of the all-atom dimers thus obtained, revealed that TM1/TM1, H8/H8,
      TM1/TM5 and TM6/TM6 regions formed most of the dimerization surfaces, which is in
      accordance with some of the experimental observations and recent simulation
      results.

PMID- 24291491
TI  - Hysteroscopic enucleation in toto of submucous type 2 myomas: long-term follow-up
      in women affected by menorrhagia.
AB  - STUDY OBJECTIVE: To evaluate long-term efficacy of type 2 myoma enucleation in
      toto. DESIGN: Longitudinal retrospective study (Canadian Task Force
      classification II-2). SETTING: University obstetrics and gynecology clinic.
      PATIENTS: One hundred twelve women with menorrhagia and at least 1 type 2
      submucous myoma who underwent hysteroscopic myoma enucleation in toto.
      INTERVENTION: Clinical long-term follow-up. MEASUREMENTS AND MAIN RESULTS:
      Success of the procedure and influence of myoma characteristics on recurrence of
      menorrhagia were evaluated. Mean (SD) follow-up was 58.4 (19.1) months. The
      success of the procedure was 88.4% (99 patients). Seventeen patients (15.2%)
      underwent a 2-step procedure. Among patients with relapsed menorrhagia, 10 (8.9%)
      underwent a repeat operation. Statistical analysis showed that number and
      diameter of myomas did not influence the outcome. Localization in the posterior
      wall of the uterus, compared with other sites, was associated with a higher
      percentage of resolution of menstrual symptoms (p = .03). There was no
      significant relationship between myomas features and risk of symptom recurrence
      during follow-up. The 2-step myomectomy was performed in patients with myomas >30
      mm in diameter (p < .001). CONCLUSION: Hysteroscopic enucleation in toto of type
      2 myomas is a safe and effective technique in long-term management of
      premenopausal women with menorrhagia.

PMID- 24291492
TI  - Prediction and verification of nonlinear sleep spindle harmonic oscillations.
AB  - This paper examines nonlinear effects in a neural field model of the
      corticothalamic system to predict the EEG power spectrum of sleep spindles.
      Nonlinearity in the thalamic relay nuclei gives rise to a spindle harmonic
      visible in the cortical EEG. By deriving an analytic expression for nonlinear
      spectrum, the power in the spindle harmonic is predicted to scale quadratically
      with the power in the spindle oscillation. By isolating sleep spindles from
      background sleep in experimental EEG data, the spindle harmonic is directly
      observed. 

PMID- 24291493
TI  - The role of the glutamatergic NMDA receptor in nanosilver-evoked neurotoxicity in
      primary cultures of cerebellar granule cells.
AB  - Nanoparticles are known to enter the vertebrate brain, but little is known about
      their neurotoxicity. The aim of this study is to investigate mechanisms of the
      contribution of AgNPs to neuronal cell death using primary cultures of rat
      cerebellar granule cells (CGCs). We tested the role of glutamatergic N-methyl-d
      aspartate receptors (NMDA) in AgNP-evoked neurotoxicity using MK-801, a
      noncompetitive inhibitor of NMDAR. We used commercially available 0.2% PVP-coated
      AgNPs <100 nm in a concentration range of 2.5-75 MUg/ml sonicated with fetal calf
      serum. After a 10 min incubation period, a dose-dependent increase in the uptake
      of (45)Ca(2+) into neurons was observed in the presence of 25-75 MUg/mL AgNPs
      which was completely abolished by addition of MK-801. Using the fluorescent dye
      fluo3 AM we observed an increase in the intracellular calcium level by 87%
      compared to control. ROS production was found to increase by about 30% over
      control after a 30-min incubation with 75 MUg/mL AgNPs. Further, we observed a
      significant decrease in the mitochondrial potential during a 30-min incubation
      with AgNPs. Administration of MK-801 was found to provide a protective effect.
      Our results show that excitotoxicity via activation of NMDA receptor, followed by
      calcium imbalance, destabilization of mitochondrial function and ROS production,
      indicate an important mechanism involved in neurotoxicity evoked by AgNPs in
      cultured neurons.

PMID- 24291494
TI  - Visual perception of materials and their properties.
AB  - Misidentifying materials-such as mistaking soap for pate, or vice versa-could
      lead to some pretty messy mishaps. Fortunately, we rarely suffer such
      indignities, thanks largely to our outstanding ability to recognize materials-and
      identify their properties-by sight. In everyday life, we encounter an enormous
      variety of materials, which we usually distinguish effortlessly and without
      error. However, despite its subjective ease, material perception poses the visual
      system with some unique and significant challenges, because a given material can
      take on many different appearances depending on the lighting, viewpoint and
      shape. Here, I use observations from recent research on material perception to
      outline a general theory of material perception, in which I suggest that the
      visual system does not actually estimate physical parameters of materials and
      objects. Instead-I argue-the brain is remarkably adept at building 'statistical
      generative models' that capture the natural degrees of variation in appearance
      between samples. For example, when determining perceived glossiness, the brain
      does not estimate parameters of the BRDF. Instead, it uses a constellation of low
      and mid-level image measurements to characterize the extent to which the surface
      manifests specular reflections. I argue that these 'statistical appearance
      models' are both more expressive and easier to compute than physical parameters,
      and therefore represent a powerful middle way between a 'bag of tricks' and
      'inverse optics'. 

PMID- 24291495
TI  - Absence of C4d urinary excretion in the early post-transplant period is
      associated with improved long-term kidney graft survival.
AB  - INTRODUCTION: C4d urinary excretion varies according to the risk of graft
      rejection or progression of chronic allograft nephropathy, but its influence on
      long-term kidney transplant (KTx) outcomes remains unclear. The aim of the study
      was to determine whether the initial (1-3 months post KTx) level of C4d urinary
      excretion may help to predict long-term kidney allograft transplantation
      outcomes. MATERIALS AND METHODS: The study involved 185 patients who had
      undergone KTx. The urinary specimens taken from the morning urine portion were
      assessed by ELISA test for C4d excretion. To increase the objectivity of the
      assessment, all measurements were divided by urinary creatinine excretion
      (ng/mgCr). The study population was grouped according to the C4d excretion cut
      off value into low (LC4d, 109 participants) and high (HC4d, 76 participants) C4d
      excretion groups. Additionally a subgroup with absence of C4d in the urine (ZC4d,
      26 patients) was formed. RESULTS: The calculated Roc curve indicated the cut off
      value of the urinary C4d excretion as 12.4ng/mgCr (AUC 0.77; 95%CI 0.73-0.95).
      The mean C4d urinary excretions in LC4d and HC4d were 1.9+/-3.27 and 20.6+/
      4.6ng/mgCr, respectively, whereas after exclusion of ZC4d subgroup, the mean C4d
      was 14.9+/-6.3ng/mgCr in the remainder. Kaplan-Meier curve analysis demonstrated
      a slightly higher graft survival rate (GSR) in LC4d than in HC4d group (p=0.04 by
      log-rank). The subsequent analysis showed the highest GSR in ZC4d subgroup
      (p=0.0006 by log-rank). CONCLUSION: Although lower C4d urinary excretion in the
      early post-transplant period seems to be associated with better long-term kidney
      allograft transplantation outcomes, only its absence in the urine appears to be a
      solid predictor of improved graft survival.

PMID- 24291496
TI  - Correlation of serum and urinary matrix metalloproteases/tissue inhibitors of
      metalloproteases with subclinical allograft fibrosis in renal transplantation.
AB  - Progressive interstitial fibrosis and tubular atrophy (IF/TA) is a leading cause
      of chronic allograft dysfunction. Increased extracellular matrix remodeling
      regulated by matrix metalloproteases (MMPs) and their inhibitors (TIMPs) has been
      implicated in the development of IF/TA. The aim of this study was to investigate
      whether urinary/serum MMPs/TIMPs correlate with subclinical IF/TA detected in
      surveillance biopsies within the first 6months post-transplant. We measured eight
      different MMPs/TIMPs simultaneously in urine and serum samples from patients
      classified as normal histology (n=15), IF/TA 1 (n=15) and IF/TA 2-3 (n=10). There
      was no difference in urinary MMPs/TIMPs among the three groups, and only 1/8
      serum MMPs/TIMPs (i.e. MMP-1) was significantly elevated in biopsies with IF/TA 2
      3 (p=0.01). In addition, urinary/serum MMPs/TIMPs were not different between
      surveillance biopsies demonstrating an early development of IF/TA (i.e. delta
      IF/TA>=1 compared to a previous biopsy obtained three months before; n=11) and
      stable grade of IF/TA (i.e. delta IF/TA=0; n=20). Next, we investigated whether
      urinary/serum MMP/TIMP levels are elevated during acute subclinical tubulitis in
      surveillance biopsies obtained within the first 6months post-transplant (n=25).
      Compared to biopsies with normal histology, serum MMPs/TIMPs were not different;
      however, all urinary MMP/TIMP levels were numerically higher during subclinical
      tubulitis (MMP-1, MMP-7, TIMP-1 with p<=0.04). We conclude that urinary/serum
      MMPs/TIMPs do hardly correlate with existing or early developing IF/TA in
      surveillance biopsies obtained within the first 6months post-transplant. This
      could be explained by the dynamic process of extracellular matrix remodeling,
      which seems to be active during acute tubulo-interstitial injury/inflammation,
      but not in quiescent IF/TA. 

PMID- 24291497
TI  - Longitudinal expression of Toll-like receptors on dendritic cells in
      uncomplicated pregnancy and postpartum.
AB  - OBJECTIVE: Toll-like receptors (TLRs) are integral parts of the innate immune
      system and have been implicated in complications of pregnancy. The longitudinal
      expression of TLRs on dendritic cells in the maternal circulation during
      uncomplicated pregnancies is unknown. The objective of this study was to
      prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal
      circulation at defined intervals throughout pregnancy and postpartum. STUDY
      DESIGN: This was a prospective cohort of 30 pregnant women with uncomplicated
      pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was
      measured in unstimulated dendritic cells at 4 defined intervals during pregnancy
      and postpartum. Basal expression of TLRs and cytokines was measured by multicolor
      flow cytometry. The percent-positive dendritic cells for each TLRs were compared
      with both nonpregnant and postpartum levels with multivariate linear regression.
      RESULTS: TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with
      persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum
      period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis
      factor alpha increased during pregnancy and returned to levels similar to
      nonpregnant controls during the postpartum period. The elevated levels of TLR 1
      and IL-12 were persistent postpartum, challenging notions that immunologic
      changes during pregnancy resolve after the prototypical postpartum period.
      CONCLUSION: Normal pregnancy is associated with time-dependent changes in TLR
      expression compared with nonpregnant controls; these findings may help elucidate
      immunologic dysfunction in complicated pregnancies.

PMID- 24291498
TI  - Kinetic and equilibrium studies of acrylonitrile binding to cytochrome c
      peroxidase and oxidation of acrylonitrile by cytochrome c peroxidase compound I.
AB  - Ferric heme proteins bind weakly basic ligands and the binding affinity is often
      pH dependent due to protonation of the ligand as well as the protein. In an
      effort to find a small, neutral ligand without significant acid/base properties
      to probe ligand binding reactions in ferric heme proteins we were led to consider
      the organonitriles. Although organonitriles are known to bind to transition
      metals, we have been unable to find any prior studies of nitrile binding to heme
      proteins. In this communication we report on the equilibrium and kinetic
      properties of acrylonitrile binding to cytochrome c peroxidase (CcP) as well as
      the oxidation of acrylonitrile by CcP compound I. Acrylonitrile binding to CcP is
      independent of pH between pH 4 and 8. The association and dissociation rate
      constants are 0.32+/-0.16 M(-1) s(-1) and 0.34+/-0.15 s(-1), respectively, and
      the independently measured equilibrium dissociation constant for the complex is
      1.1+/-0.2 M. We have demonstrated for the first time that acrylonitrile can bind
      to a ferric heme protein. The binding mechanism appears to be a simple, one-step
      association of the ligand with the heme iron. We have also demonstrated that CcP
      can catalyze the oxidation of acrylonitrile, most likely to 2-cyanoethylene oxide
      in a "peroxygenase"-type reaction, with rates that are similar to rat liver
      microsomal cytochrome P450-catalyzed oxidation of acrylonitrile in the
      monooxygenase reaction. CcP compound I oxidizes acrylonitrile with a maximum
      turnover number of 0.61 min(-1) at pH 6.0.

PMID- 24291499
TI  - Midkine exacerbates pressure overload-induced cardiac remodeling.
AB  - Midkine is a multifunctional growth factor, and its serum levels are increased
      with the functional severity of heart failure. This study aimed to examine the
      role of midkine in heart failure pathogenesis. Midkine expression levels were
      increased in the kidney and lung after transverse aortic constriction (TAC)
      surgery, but not sufficiently increased in the heart. After TAC, phosphorylation
      of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of
      foetal genes in the heart were considerably increased in transgenic mice with
      cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT)
      mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and
      showed lower survival rate after TAC than WT mice. We conclude that midkine plays
      a critical role in cardiac hypertrophy and remodelling. 

PMID- 24291501
TI  - P1 and P1' para-fluoro phenyl groups show enhanced binding and favorable
      predicted pharmacological properties: structure-based virtual screening of
      extended lopinavir analogs against multi-drug resistant HIV-1 protease.
AB  - Crystal structure of multidrug-resistant (MDR) clinical isolate 769, human
      immunodeficiency virus type-1 (HIV-1) protease in complex with lopinavir (LPV)
      (PDB ID: 1RV7) showed altered binding orientation of LPV in the expanded active
      site cavity, causing loss of contacts and decrease in potency. In the current
      study, with a goal to restore the lost contacts, three libraries of LPV analogs
      containing extended P1 and/or P1' phenyl groups were designed and docked into the
      expanded active site cavity of the MDR769 HIV-1 protease. The compounds were then
      ranked based on three criteria: binding affinity, overall binding profile and
      predicted pharmacological properties. Among the twelve proposed extensions in
      different combinations, compound 14 (consists of para-fluoro phenyl group as both
      P1 and P1' moieties) was identified as a lead with improved binding profile,
      binding affinity against the MDR protease and favorable predicted pharmacological
      properties comparable to those of LPV. The binding affinity of 14 against wild
      type (NL4-3) HIV-1 protease was comparable to that of LPV and was better than LPV
      against an ensemble of MDR HIV-1 protease variants. Thus, 14 shows enhanced
      binding affinity by restoring lost contacts in the expanded active site cavity of
      MDR769 HIV-1 protease variants suggesting that it may have higher potency
      compared to that of LPV and hence should be further synthesized and evaluated
      against NL4-3 as well as MDR variants of HIV-1. 

PMID- 24291500
TI  - Activation of farnesoid X receptor induces RECK expression in mouse liver.
AB  - Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor
      superfamily, and functions as a transcription factor regulating the transcription
      of numerous genes involved in bile acid homeostasis, lipoprotein and glucose
      metabolism. In the present study, we identified RECK, a membrane-anchored
      inhibitor of matrix metalloproteinases, as a novel target gene of FXR in mouse
      liver. We found that FXR agonist substantially augmented hepatic RECK mRNA and
      protein expression in vivo and in vitro. FXR regulated the transcription of RECK
      through directly binding to FXR response element located within intron 1 of the
      mouse RECK gene. Moreover, FXR agonist reversed the down-regulation of RECK in
      the livers from mice fed a methionine and choline deficient diet. In summary, our
      data suggest that RECK is a novel transcriptional target of FXR in mouse liver,
      and provide clues to better understanding the function of FXR in liver. 

PMID- 24291502
TI  - Where agreement merges with disagreement: fMRI evidence of subject-verb
      integration.
AB  - Language comprehension is incremental, involving the integration of information
      from different words together with the need to resolve conflicting cues when
      unexpected information occurs. The present fMRI design seeks to segregate the
      neuro-anatomical substrates of these two processes by comparing well-formed and
      ill-formed sentences during subject-verb agreement computation. Our experiment
      takes advantage of a particular Spanish feature, the Unagreement phenomenon: a
      subject-verb agreement mismatch that results in a grammatical sentence ("Los
      pintores trajimos..." [The painters3.pl (we)brought1.pl...]). Comprehension of
      this construction implies a shift in the semantic interpretation of the subject
      from 3rd-person to 1st-person, enabling the phrase "The painters" to be re
      interpreted as "We painters". Our results include firstly a functional
      dissociation between well-formed and ill-formed sentences with Person Mismatches:
      while Person Mismatches recruited a fronto-parietal network associated to
      monitoring operations, grammatical sentences (both Unagreement and Default
      Agreement) recruited a fronto-temporal network related to syntactic-semantic
      integration. Secondly, there was activation in the posterior part of the left
      middle frontal gyrus for both Person Mismatches and Unagreement, reflecting the
      evaluation of the morpho-syntactic match between agreeing constituents. Thirdly,
      the left angular gyrus showed increased activation only for Unagreement,
      highlighting its crucial role in the comprehension of semantically complex but
      non-anomalous constructions. These findings point to a central role of the
      classic fronto-temporal network, plus two additional nodes: the posterior part of
      the left middle frontal gyrus and the left angular gyrus; opening new windows to
      the study of agreement computation and language comprehension.

PMID- 24291503
TI  - The SEMA5A gene is associated with hippocampal volume, and their interaction is
      associated with performance on Raven's Progressive Matrices.
AB  - The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes
      an important protein for neurogenesis and neuronal apoptosis, is predominantly
      expressed in the human hippocampus. Structural and functional neuroimaging
      studies have further shown that the hippocampus plays an important role in the
      performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability
      and general fluid intelligence. Thus far, however, no study has examined the
      relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM
      performance. The current study collected both structural MRI, genetic, and
      behavioral data in 329 healthy Chinese adults, and examined associations between
      SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form
      of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A
      genetic polymorphism at the SNP rs42352 had the strongest association with
      hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal
      volumes, respectively), with TT homozygotes having higher hippocampal volume than
      the other genotypes. Furthermore, there was a high correlation between right
      hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352
      TT homozygotes. This study provides the first evidence for the involvement of the
      SEMA5A gene in hippocampal structure and their interaction on RAPM performance.
      Future studies of the hippocampus-RPM associations should consider genetic
      factors as potential moderators.

PMID- 24291504
TI  - Fatal attraction: ventral striatum predicts costly choice errors in humans.
AB  - Animals approach rewards and cues associated with reward, even when this behavior
      is irrelevant or detrimental to the attainment of these rewards. Motivated by
      these findings we study the biology of financially-costly approach behavior in
      humans. Our subjects passively learned to predict the occurrence of erotic
      rewards. We show that neuronal responses in ventral striatum during this
      Pavlovian learning task stably predict an individual's general tendency towards
      financially-costly approach behavior in an active choice task several months
      later. Our data suggest that approach behavior may prevent some individuals from
      acting in their own interests. 

PMID- 24291505
TI  - Missing data in a multi-item instrument were best handled by multiple imputation
      at the item score level.
AB  - OBJECTIVES: Regardless of the proportion of missing values, complete-case
      analysis is most frequently applied, although advanced techniques such as
      multiple imputation (MI) are available. The objective of this study was to
      explore the performance of simple and more advanced methods for handling missing
      data in cases when some, many, or all item scores are missing in a multi-item
      instrument. STUDY DESIGN AND SETTING: Real-life missing data situations were
      simulated in a multi-item variable used as a covariate in a linear regression
      model. Various missing data mechanisms were simulated with an increasing
      percentage of missing data. Subsequently, several techniques to handle missing
      data were applied to decide on the most optimal technique for each scenario.
      Fitted regression coefficients were compared using the bias and coverage as
      performance parameters. RESULTS: Mean imputation caused biased estimates in every
      missing data scenario when data are missing for more than 10% of the subjects.
      Furthermore, when a large percentage of subjects had missing items (>25%), MI
      methods applied to the items outperformed methods applied to the total score.
      CONCLUSION: We recommend applying MI to the item scores to get the most accurate
      regression model estimates. Moreover, we advise not to use any form of mean
      imputation to handle missing data.

PMID- 24291506
TI  - A users' guide to understanding therapeutic substitutions.
AB  - Therapeutic substitutions are common at the level of ministries of health,
      clinicians, and pharmacy dispensaries. Guidance in determining whether drugs
      offer similar risk-benefit profiles is limited. Those making decisions on
      therapeutic substitutions should be aware of potential biases that make
      differentiating therapeutic agents difficult. Readers should consider whether the
      biological mechanisms and doses are similar across agents, whether the evidence
      is sufficiently valid across agents, and whether the safety and therapeutic
      effects of each drug are similar. This article uses a problem-based format to
      address the biological mechanism, validity, and results of a scenario in which
      therapeutic substitutions may be considered.

PMID- 24291507
TI  - Morphology and ultrastructural studies of pineal organ of the tree sparrow
      (Passer montanus).
AB  - We studied fine structures of the pineal organ of the tree sparrow, Passer
      montanus under the light, scanner electron and transmission electron microscopes.
      The pineal gland of the sparrow was found comprising of a pea-shaped epiphysis
      cerebri and a long tube-like pineal stalk that connects with the choroid plexus.
      Histological preparations of the pineal organ revealed that it contains follicles
      having pinealocytes of uniform size. The enlarged images of the gland using the
      SEM showed distinct granular structures or cells protruding from the surface of
      the epiphysis cerebri. The choroid plexus possessed varying numbers of irregular
      ridges and furrows. The observation under TEM revealed rounded nucleus and
      mitochondria in the pinealocytes. Groups of small size vesicles were also seen
      scattered throughout the perinuclear cytoplasm. Numbers of microtubules were
      found running parallel to each other. Blood capillaries that supply blood to the
      pineal organ were also visible in the sections. The morphology of the pineal
      organ of tree sparrow showed similarity with those of the other birds in
      possessing elongated epiphysis cerebri which remains connected to choroid plexus
      through a stalk. The tree sparrow resembled with some passerine birds in
      possessing saccular type of pineal organ having elongated tubular structure with
      a central lumen and a thick follicular wall. The pineal organ of the tree
      sparrow, thus, differed from those reported in non-passerine birds with tubulo
      follicular or solid type of pineal organ. The presence of saccular pineal organ
      in the subtropical tree sparrow, as reported in other passerine birds elsewhere
      indicates the conservation of the structural organization of the pineal organ in
      passerine birds. 

PMID- 24291508
TI  - Isolation and molecular analysis of porcine encephalomyocarditis virus strain BD2
      from northern China.
AB  - Encephalomyocarditis virus (EMCV) can cause acute myocarditis in young pigs or
      reproductive failure in sows. In this study, an EMCV strain (BD2) was isolated
      from the suspected piglets with EMCV in China. It was identified by an indirect
      immunofluorescence assay and reverse-transcription polymerase chain reaction. The
      virus could reproduce on BHK-21 cells and reach a peak titer by 16 hpi with
      maximum titers of 10(8.22)TCID50/0.1 ml. Phylogenetic analyses of open reading
      frame and the VP3/VP1 genes using neighbor-joining method revealed that EMCV
      isolates fell into two clusters: groups I and II. The BD2 isolate belonged to
      group I, along with strains NJ08, HB1, BJC3, CBNU, K3, K11, BEL-2887A, GX0601,
      GXLC, pEC9, and PV21, whereas four strains (D variant, EMCV-B, EMCV-D, and PV2)
      belonged to group II.

PMID- 24291509
TI  - Life after cardiac arrest: better with time.

PMID- 24291510
TI  - Do dispatcher instructions facilitate bystander-initiated cardiopulmonary
      resuscitation and improve outcomes in patients with out-of-hospital cardiac
      arrest? A comparison of family and non-family bystanders.
AB  - OBJECTIVES: Bystander-initiated cardiopulmonary resuscitation (CPR) has been
      reported to increase the possibility of survival in patients with out-of-hospital
      cardiopulmonary arrest (OHCA). We evaluated the effects of CPR instructions by
      emergency medical dispatchers on the frequency of bystander CPR and outcomes, and
      whether these effects differed between family and non-family bystanders. METHODS:
      We conducted a retrospective cohort study, using Utstein-style records of OHCA
      taken in a rural area of Japan between January 2004 and December 2009. RESULTS:
      Of the 559 patients with non-traumatic OHCA witnessed by laypeople, 231 (41.3%)
      were given bystander CPR. More OHCA patients received resuscitation when the OHCA
      was witnessed by non-family bystanders than when it was witnessed by family
      members (61.4% vs. 34.2%). The patients with non-family-witnessed OHCA were more
      likely to be given conventional CPR (chest compression plus rescue breathing) or
      defibrillation with an AED than were those with family-witnessed OHCA. Dispatcher
      instructions significantly increased the provision of bystander CPR regardless of
      who the witnesses were. Neurologically favorable survival was increased by CPR in
      non-family-witnessed, but not in family-witnessed, OHCA patients. No difference
      in survival rate was observed between the cases provided with dispatcher
      instructions and those not provided with the instructions. CONCLUSIONS:
      Dispatcher instructions increased the frequency of bystander CPR, but did not
      improve the rate of neurologically favorable survival in patients with witnessed
      OHCA. Efforts to enhance the frequency and quality of resuscitation, especially
      by family members, are required for dispatcher-assisted CPR.

PMID- 24291511
TI  - Neonatal resuscitation skills amongst healthcare workers in Bo district, Sierra
      Leone.

PMID- 24291512
TI  - Prism adaptation in the healthy brain: the shift in line bisection judgments is
      long lasting and fluctuates.
AB  - Rightward prism adaptation has been shown to ameliorate visuospatial biases in
      right brain-damaged patients with neglect, and a single session of prism
      adaptation can lead to improvements that last up to several hours. Leftward prism
      adaptation in neurologically healthy individuals induces neglect-like biases in
      visuospatial tasks. The duration of these effects in healthy individuals,
      typically assumed to be ephemeral, has never been investigated. Here we assessed
      the time-course of the adaptation-induced modifications in a classical perceptual
      line bisection task that was repeatedly administered for approximately 40min
      after a single session of adaptation to either a leftward or rightward prismatic
      deviation. Consistent with previous reports, only adaptation to leftward
      deviating prisms induced a visuospatial shift on perceptual line bisection
      judgments. The typical pattern of pseudoneglect was counteracted by a rightward
      shift in midline judgments, which became significant between 5 and 10 min after
      adaptation, fluctuated between being significant or not several times in the 40
      min following adaptation, and was present as late as 35 min. In contrast, the
      sensorimotor aftereffect was present immediately after adaptation to both
      rightward and leftward deviating prisms, decayed initially then remained stable
      until 40 min. These results demonstrate that both the sensorimotor and
      visuospatial effects last for at least 35 min, but that the visuospatial shift
      needs time to fully develop and fluctuates. By showing that the effects of prism
      adaptation in the undamaged brain are not ephemeral, these findings reveal the
      presence of another, so-far neglected dimension in the domain of the cognitive
      effects induced by prism adaptation, namely time. The prolonged duration of the
      induced visuospatial shift, previously considered to be a feature of prism
      adaptation unique to brain-damaged subjects, also applies to the normal brain.

PMID- 24291513
TI  - Oscillatory brain responses in spoken word production reflect lexical frequency
      and sentential constraint.
AB  - Two fundamental factors affecting the speed of spoken word production are lexical
      frequency and sentential constraint, but little is known about their timing and
      electrophysiological basis. In the present study, we investigated event-related
      potentials (ERPs) and oscillatory brain responses induced by these factors, using
      a task in which participants named pictures after reading sentences. Sentence
      contexts were either constraining or nonconstraining towards the final word,
      which was presented as a picture. Picture names varied in their frequency of
      occurrence in the language. Naming latencies and electrophysiological responses
      were examined as a function of context and lexical frequency. Lexical frequency
      is an index of our cumulative learning experience with words, so lexical
      frequency effects most likely reflect access to memory representations for words.
      Pictures were named faster with constraining than nonconstraining contexts.
      Associated with this effect, starting around 400 ms pre-picture presentation,
      oscillatory power between 8 and 30 Hz was lower for constraining relative to
      nonconstraining contexts. Furthermore, pictures were named faster with high
      frequency than low-frequency names, but only for nonconstraining contexts,
      suggesting differential ease of memory access as a function of sentential
      context. Associated with the lexical-frequency effect, starting around 500 ms pre
      picture presentation, oscillatory power between 4 and 10 Hz was higher for high
      frequency than for low-frequency names, but only for constraining contexts. Our
      results characterise electrophysiological responses associated with lexical
      frequency and sentential constraint in spoken word production, and point to new
      avenues for studying these fundamental factors in language production.

PMID- 24291514
TI  - Classification of washing powder brands using near-infrared spectroscopy combined
      with chemometric calibrations.
AB  - In this study, near-infrared (NIR) spectroscopy is applied for rapid and
      objective classification of 5 different brands of washing powder. Chemometric
      calibrations including partial least square discriminant analysis (PLS-DA), back
      propagation neural network (BP-NN) and least square support vector machine (LS
      SVM) are investigated and compared to achieve an optimal result. Firstly,
      principal component analysis (PCA) is conducted to visualize the difference among
      washing powder samples of different brands and principal components (PCs) are
      extracted as inputs of BP-NN and LS-SVM models. The number of PCs and parameters
      of such models are optimized via cross validation. In experimental studies, a
      total of 225 spectra of washing powder samples (45 samples for each brand) were
      used to build models and 75 spectra of washing powder samples (15 samples for
      each brand) were used as the validation set to evaluate the performance of
      developed models. As for the comparison of the three investigated models, both BP
      NN model and LS-SVM model successfully classified all samples in validation set
      according to their brands. However, the PLS-DA model failed to achieve 100% of
      classification accuracy. The results obtained in this investigation demonstrate
      that NIR spectroscopy combined with chemometric calibrations including BP-NN and
      LS-SVM can be successfully utilized to classify the brands of washing powder. 

PMID- 24291515
TI  - Spectrophotometric determination of acidity constants of 2-(2-Thiazolylazo)
      Cresol in various water-organic solvent media mixtures using chemometrics
      methods.
AB  - The combination of soft- and hard-modeling was used to the spectrophotometric
      studies of the acidity constants of 2-(2-Thiazolylazo)-Cresol (TAC) at 25 degrees
      C and at ionic strength 0.1 mol L(-1) in pure water as well as in aqueous media
      containing variable percentages (10-50%) of organic solvents. The organic
      solvents used were methanol, ethanol, dimethyl formamide (DMF) and 1,4-dioxane.
      The acidity constants of all related equilibria are estimated using the whole
      spectral fitting of the collected data to an established factor analysis model.
      DATAN program was applied for determining acidity constants and pure spectra of
      different form of TAC. Results show that the acidity constants of TAC are
      influenced as the percentages of solvents added to the solution. The
      corresponding pKa values in solvent-water mixtures were determined. There are
      linear relationships between acidity constants and the mole fraction of organic
      solvents in the solvent mixtures. The effects of various solvents on absorption
      properties and acidity constants of each component are also discussed.

PMID- 24291516
TI  - Comparative studies and modeling structures of two new isomers containing
      binuclear PdII complexes derived from 2,4,6-tri-(2-pyridyl)-1,3,5-triazine
      (TPTZ).
AB  - The synthesis and comparative studies of two new binuclear PdII isomer complexes
      derived from TPTZ, [2,4,6-tri-(2-pyridyl)-1,3,5-triazine], have been synthesized
      and characterized. Their structures have been investigated by elemental analyses,
      spectral (IR, UV-vis, mass and 1H-NMR) and thermal measurements. Electronic and
      magnetic studies suggest a distorted square-planar around the two PdII ions. The
      HOMO, LUMO and DFT parameters on the atoms have been calculated to confirm the
      geometry of the ligand and their complexes. Kinetic parameters were determined
      using Coats-Redfern and Horowitz-Metzger methods. Also, the geometry of the two
      isomers is confirmed using DFT method from DMOL3 calculations. Moreover, the two
      PdII complexes have different specific optical rotation where the red PdII
      complex has dextrorotatory (+5.68) while the yellow PdII complex has levorotatory
      (-9.37). The results of biological activity for the two PdII complexes promised
      to be effective in tumor treatment.

PMID- 24291517
TI  - Disrupted cross-laminar cortical processing in beta amyloid pathology precedes
      cell death.
AB  - Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly
      recognized as a key correlate of cognitive and memory decline in Alzheimer
      patients. We hypothesized that functional synaptic disconnections within cortical
      columnar microcircuits by pathological beta-amyloid accumulation, rather than
      cell death, initially causes the cognitive impairments. During development of
      cortical beta-amyloidosis with still few plaques in the transgenic 5xFAD mouse
      model single cell resolution mapping of neuronal thallium uptake revealed that
      electrical activity of pyramidal cells breaks down throughout infragranular
      cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the
      glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of
      pyramidal cell activity, indicating pyroglutamate-modified forms, potentially
      mixed oligomers of Abeta are contributing to neuronal impairment. Laminar
      investigation of cortical circuit dysfunction with current source density
      analysis identified an early loss of excitatory synaptic input in infragranular
      layers, linked to pathological recurrent activations in supragranular layers.
      This specific disruption of normal cross-laminar cortical processing coincided
      with a decline of contextual fear learning. 

PMID- 24291518
TI  - Developmental molecular and functional cerebellar alterations induced by
      PCP4/PEP19 overexpression: implications for Down syndrome.
AB  - PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed
      in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly
      expressed in the Purkinje cell, the sole output neuron of the cerebellum. PCP4,
      located on human chromosome 21, is present in three copies in individuals with
      Down syndrome (DS). In a previous study using a transgenic mouse model (TgPCP4)
      to evaluate the consequences of 3 copies of this gene, we found that PCP4
      overexpression induces precocious neuronal differentiation during mouse
      embryogenesis. Here, we report combined analyses of the cerebellum at postnatal
      stages (P14 and adult) in which we identified age-related molecular,
      electrophysiological, and behavioral alterations in the TgPCP4 mouse. While Pcp4
      overexpression at P14 induces an earlier neuronal maturation, at adult stage it
      induces increase in cerebellar CaMK2alpha and in cerebellar LTD, as well as
      learning impairments. We therefore propose that PCP4 contributes significantly to
      the development of Down syndrome phenotypes through molecular and functional
      changes. 

PMID- 24291519
TI  - Drosophila Myc, a novel modifier suppresses the poly(Q) toxicity by modulating
      the level of CREB binding protein and histone acetylation.
AB  - Polyglutamine or poly(Q) disorders are dominantly inherited neurodegenerative
      diseases characterised by progressive loss of neurons in cerebellum, basal
      ganglia and cortex in adult human brain. Overexpression of human form of mutant
      SCA3 protein with 78 poly(Q) repeats leads to the formation of inclusion bodies
      and increases the cellular toxicity in Drosophila eye. The present study was
      directed to identify a genetic modifier of poly(Q) diseases that could be
      utilised as a potential drug target. The initial screening process was influenced
      by the fact of lower prevalence of cancer among patients suffering with poly(Q)
      disorders which appears to be related to the intrinsic biological factors. We
      investigated if Drosophila Myc (a homologue of human cMyc proto-oncogene)
      harbours intrinsic property of suppressing cellular toxicity induced by an
      abnormally long stretch of poly(Q). We show for the first time that targeted
      overexpression of Drosophila Myc (dMyc) mitigates the poly(Q) toxicity in eye and
      nervous systems. Upregulation of dMyc results in a significant reduction in
      accumulation of inclusion bodies with residual poly(Q) aggregates localising into
      cytoplasm. We demonstrate that dMyc mediated suppression of poly(Q) toxicity is
      achieved by alleviating the cellular level of CBP and improved histone
      acetylation, resulting restoration of transcriptional machinery which are
      otherwise abbreviated due to poly(Q) disease conditions. Moreover, our study also
      provides a rational justification of the enigma of poly(Q) patients showing
      resistance to the predisposition of cancer. 

PMID- 24291520
TI  - Macular dystrophies mimicking age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in the elderly population in the Western world. AMD is a clinically
      heterogeneous disease presenting with drusen, pigmentary changes, geographic
      atrophy and/or choroidal neovascularization. Due to its heterogeneous
      presentation, it can be challenging to distinguish AMD from several macular
      diseases that can mimic the features of AMD. This clinical overlap may
      potentially lead to misdiagnosis. In this review, we discuss the characteristics
      of AMD and the macular dystrophies that can mimic AMD. The appropriate use of
      clinical and genetic analysis can aid the clinician to establish the correct
      diagnosis, and to provide the patient with the appropriate prognostic
      information. An overview is presented of overlapping and distinguishing clinical
      features. 

PMID- 24291521
TI  - Changes in daily activity patterns of caregivers of children with newly diagnosed
      epilepsy: a case-controlled design.
AB  - Having a child diagnosed with a chronic pediatric illness is a major stressor for
      families that can alter their daily lives. The primary study aim was to use Daily
      Phone Diaries (DPDs), a cued-recall procedure to track parents through their
      activities over a 24-hour period, to assess the activity patterns of a group of
      caregivers with a child diagnosed with new-onset epilepsy (group with NOE; n=30)
      and a group of matched comparisons (comparison group; n=29). The time caregivers
      spent in sleep and recreation was evaluated over the first 5.5months after
      diagnosis. Caregivers of children with NOE spent significantly more time in
      recreation inside the home, while the comparison group spent significantly more
      time in recreation outside the home. These data suggest that families with
      children with NOE reallocate their time post-diagnosis from recreation outside to
      inside the home, which raises concerns about the overall adaptation of the family
      to the diagnosis and presents a critical opportunity for health-care teams to
      intervene and support families with children with NOE. 

PMID- 24291522
TI  - Late-onset seizures and risk of subsequent stroke: a systematic review.
AB  - Otherwise unexplained late-onset seizures, conventionally defined as epileptic
      seizures occurring in subjects older than 60years and in the absence of disorders
      known to increase the risk of developing epilepsy, have been assumed to be, in
      most cases, of cerebrovascular origin. We systematically searched the literature
      to identify the evidence supporting the association between otherwise unexplained
      late-onset seizures/epilepsy and the risk of subsequent stroke. Most data from
      the literature indicate that cerebrovascular disease often underlies otherwise
      unexplained late-onset seizures/epilepsy. Patients presenting with seizures
      occurring for the very first time in late life and without clinically overt
      cerebrovascular disease should be considered as at increased risk of stroke.
      Consequently, these patients should be screened for the presence of vascular risk
      factors and treated accordingly. Such measures may greatly contribute to prevent
      strokes in these patients. 

PMID- 24291523
TI  - Intractable epilepsy: deep brain stimulation (DBS)-based electrophysiological
      biomarker.

PMID- 24291524
TI  - Correlation between interictal cerebral glucose hypometabolism and IQ in children
      with epilepsy.
AB  - The aim of this study was to understand the relationship between IQ and glucose
      metabolism in brain cells in a wide variety of subjects with epilepsy. The study
      participants were 78 children with epilepsy and 15 healthy children for
      comparison. All participants were administered the Chinese Wechsler Intelligence
      Scale for Children (C-WISC). The verbal intelligence quotient (VIQ), performance
      intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were
      compared between children with epilepsy and typically developing children.
      Seventy-eight patients underwent interictal positron emission computed tomography
      (PET) using 2-deoxy-2[(18)F]fluoro-d-glucose (FDG) as the tracer for evaluating
      brain glucose metabolism. Verbal intelligence quotient, PIQ, and FIQ based on the
      C-WISC were significantly lower in children with epilepsy than those in the
      healthy comparison group (P<0.001, P=0.001, and P<0.001, respectively). The IQ of
      patients with normal metabolism, unifocal abnormal hypometabolism, and multifocal
      abnormal hypometabolism determined by PET differed significantly. The extent of
      the abnormal hypometabolism was negatively correlated with the FIQ (rs=-0.549,
      P<0.001). In patients with lateralized hypometabolism based on PET, the VIQ/PIQ
      discrepancy scores (|VIQ-PIQ|>=15 points) differed significantly between the left
      hemisphere abnormal hypometabolism and right hemisphere abnormal hypometabolism
      subgroups, with negative values in the left and positive values in the right
      subgroups (P=0.004). In conclusion, brain metabolic abnormalities are correlated
      with IQ, and performing interictal PET along with C-WISC can better assess the
      extent of severity of cognitive impairment and VIQ/PIQ discrepancy. 

PMID- 24291526
TI  - Use of a Si(Li) detector as beta spectrometer.
AB  - The aim of this work is to demonstrate the capability of a Si(Li) detector for
      the measurement of beta spectra, despite the energy absorption in air and in the
      Be window. A simple source holder fixes the source on the symmetry axis at 3mm
      from the detector window. The beta-sources are produced by evaporation on a
      plastic backing plate. Absorbing materials between the source and the sensitive
      volume of the detector are 3 mm of air, a Be window, 0.1 MUm Si and 20 nm of
      gold. A model of the detector was created for beta spectra simulation using the
      MCNP 4A code. Experimental spectra of (14)C, (147)Pm, (204)Tl, (90)Sr/(90)Y were
      compared with simulated spectra.

PMID- 24291525
TI  - Influence of anxiety on memory performance in temporal lobe epilepsy.
AB  - This study examined the degree to which anxiety contributed to inconsistent
      material-specific memory difficulties among 243 patients with temporal lobe
      epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey
      Complex Figure Test (RCFT) was poorer for those with high versus low levels of
      anxiety but was not found to be related to the TLE side. The verbal memory score
      on the California Verbal Learning Test (CVLT) was significantly lower for
      patients with left-sided TLE than for patients with right-sided TLE with low
      anxiety levels but equally impaired for those with high anxiety levels. These
      results suggest that we can place more confidence in the ability of verbal memory
      tests like the CVLT to lateralize to left-sided TLE for those with low anxiety
      levels, but that verbal memory will be less likely to produce lateralizing
      information for those with high anxiety levels. This suggests that more caution
      is needed when interpreting verbal memory tests for those with high anxiety
      levels. These results indicated that RCFT performance was significantly affected
      by anxiety and did not lateralize to either side, regardless of anxiety levels.
      This study adds to the existing literature which suggests that drawing-based
      visual memory tests do not lateralize among patients with TLE, regardless of
      anxiety levels. 

PMID- 24291527
TI  - Can the ZoMBieS method be used to characterise scintillator non-linearity?
AB  - Measurements of the detection efficiency as a function of deposited electron
      energy in a liquid scintillation cocktail between 4 keV and 49 keV are obtained
      using the ZoMBieS method. Comparison is made between the measured data and the
      Poisson-Birks detection efficiency model. Measurements of the Birks non-linearity
      parameter, kB, and the linearised scintillation response of each photomultiplier,
      omega(i), were made using these data. However, the value of kB that best
      linearises the scintillator response is found to vary depending upon which
      photomultiplier is used in its determination, and the measured kB and omega(i)
      vary depending on the external source geometry. The cause of this behaviour is
      unknown. The triple-coincident detection efficiency appears to be unaffected by
      any systematic errors.

PMID- 24291529
TI  - A magnet system for the suppression of conversion electrons in alpha
      spectrometry.
AB  - A new magnet system has been designed and constructed to reduce coincidence
      effects between alpha particles and conversion electrons in high-resolution alpha
      particle spectrometry. By means of a magnetic field, the conversion electrons are
      deflected away from the PIPS((r)) detector. Compared to existing magnet systems,
      the new system is not restricted to point sources and can accommodate source
      diameters up to about 30 mm. Two yokes were built, allowing for configurations
      with 20 mm or 36 mm distance between the magnets. The effectiveness of both
      configurations is demonstrated by measuring the conversion electron spectrum of a
      (237)Np source. The magnet system effectively rejects 93 (7)% of electrons up to
      85 keV (36 mm) and 90 (9)% of electrons up to 320 keV (20 mm). It has been
      successfully applied in the alpha-particle spectrometry of the long-lived
      nuclides (236)U and (238)U, resulting in significant improvement of the accuracy
      of alpha emission probabilities.

PMID- 24291528
TI  - Certified Reference Material IAEA-446 for radionuclides in Baltic Sea seaweed.
AB  - A Certified Reference Material (CRM) for radionuclides in seaweed (Fucus
      vesiculosus) from the Baltic Sea (IAEA-446) is described and the results of the
      certification process are presented. The (40)K, (137)Cs, (234)U and (239+240)Pu
      radionuclides were certified for this material, and information values for 12
      other radionuclides ((90)Sr, (99)Tc, (210)Pb ((210)Po), (226)Ra, (228)Ra,
      (228)Th, (230)Th, (232)Th, (235)U, (238)U, (239)Pu and (240)Pu) are presented.
      The CRM can be used for Quality Assurance/Quality Control of analysis of
      radionuclides in seaweed and other biota samples, as well as for development and
      validation of analytical methods, and for training purposes. 

PMID- 24291530
TI  - Recurrent pulmonary exacerbations are associated with low fat free mass and low
      bone mineral density in young adults with cystic fibrosis.
AB  - BACKGROUND: In cystic fibrosis (CF), systemic inflammation and pulmonary
      infections sustain a catabolic response leading to fat free mass (FFM) depletion.
      OBJECTIVES: To investigate the association between recurrent pulmonary
      exacerbations and alteration in body composition in young adults with CF.
      METHODS: In a retrospective study we collected body composition data, obtained by
      DXA scan, on 85 young adults with CF (44 males, mean age 23+/-4years). Whole body
      and appendicular FFM were divided by height squared to obtain FFM indices (FFMI).
      Number of pulmonary exacerbations occurred in the year preceding DXA scan were
      computed and patients were defined as frequent exacerbators if they experienced
      more than 2 pulmonary exacerbations/year. Body composition data were compared
      between frequent and infrequent exacerbators. RESULTS: Male patients classified
      as frequent exacerbators had lower total body bone mineral density (Z-score 
      1.44+/-1.22 vs. -0.66+/-0.92, P=0.033), whole body FFMI (18.0+/-1.9kg/m(2) vs.
      19.3+/-1.4kg/m(2), P=0.024) and appendicular FFMI (7.8+/-1.0kg/m(2) vs. 8.8+/
      0.8kg/m(2)P=0.004) compared to infrequent exacerbators. The reduced FFM found in
      frequent exacerbators was not uniformly distributed and involved mainly
      appendicular FFM (mean difference: -11% compared to infrequent exacerbators,
      P=0.016), whereas trunk FFM was not significantly affected by pulmonary
      exacerbations (mean difference -3% compared to infrequent exacerbators, P=0.34).
      These differences were not found in female patients. CONCLUSIONS: Recurrent
      pulmonary exacerbations are associated with reduced appendicular FFM and bone
      mineral density in young male adults with CF. The gender-dependent relationship
      between pulmonary exacerbations and body composition alteration needs to be
      further investigated.

PMID- 24291531
TI  - Reconciling phonological neighborhood effects in speech production through single
      trial analysis.
AB  - A crucial step for understanding how lexical knowledge is represented is to
      describe the relative similarity of lexical items, and how it influences language
      processing. Previous studies of the effects of form similarity on word production
      have reported conflicting results, notably within and across languages. The aim
      of the present study was to clarify this empirical issue to provide specific
      constraints for theoretical models of language production. We investigated the
      role of phonological neighborhood density in a large-scale picture naming
      experiment using fine-grained statistical models. The results showed that
      increasing phonological neighborhood density has a detrimental effect on naming
      latencies, and re-analyses of independently obtained data sets provide
      supplementary evidence for this effect. Finally, we reviewed a large body of
      evidence concerning phonological neighborhood density effects in word production,
      and discussed the occurrence of facilitatory and inhibitory effects in accuracy
      measures. The overall pattern shows that phonological neighborhood generates two
      opposite forces, one facilitatory and one inhibitory. In cases where speech
      production is disrupted (e.g. certain aphasic symptoms), the facilitatory
      component may emerge, but inhibitory processes dominate in efficient naming by
      healthy speakers. These findings are difficult to accommodate in terms of
      monitoring processes, but can be explained within interactive activation accounts
      combining phonological facilitation and lexical competition. 

PMID- 24291533
TI  - Pharmacoperones and the calcium sensing receptor: exogenous and endogenous
      regulators.
AB  - Calcium sensing receptor (CaSR) mutations or altered expression cause disorders
      of calcium handling. Recent studies suggest that reduced targeting to the plasma
      membrane is a feature common to many CaSR loss-of-function mutations. Allosteric
      agonists (calcimimetics) can rescue signaling of a subset of CaSR mutants. This
      review evaluates our current understanding of the subcellular site(s) for
      allosteric modulator rescue of CaSR mutants. Studies to date make a strong case
      for calcimimetic potentiation of signaling not only at plasma membrane-localized
      CaSR, but at the endoplasmic reticulum, acting as pharmacoperones to assist in
      navigation of multiple quality control checkpoints. The possible role of
      endogenous pharmacoperones, calcium and glutathione, in folding and stabilization
      of the CaSR extracellular and transmembrane domains are considered. Finally, the
      possibility that dihydropyridines act as unintended pharmacoperones of CaSR is
      proposed. While our understanding of pharmacoperone rescue of CaSR requires
      refinement, promising results to date argue that this may be a fruitful avenue
      for drug discovery. 

PMID- 24291534
TI  - Glibenclamide improves kidney and heart structure and function in the adenine
      diet model of chronic kidney disease.
AB  - The development of chronic kidney disease (CKD) and associated cardiovascular
      disease involves free radical damage and inflammation. Addition of adenine to the
      diet induces inflammation followed by CKD and cardiovascular disease. NOD-like
      receptor protein-3 (NLRP-3) is pro-inflammatory in the kidney; glibenclamide
      inhibits production of NLRP-3. Male Wistar rats were fed either control rat food
      or adenine (0.25%) in this food for 16 weeks. Glibenclamide (10 mg/kg/day) was
      administered to two groups with and without adenine for the final 8 weeks. Kidney
      function (blood urea nitrogen/BUN, plasma creatinine/PCr, plasma uric acid,
      proteinuria), kidney structure (fibrosis, inflammation), cardiovascular
      parameters (blood pressure, left ventricular stiffness, vascular responses and
      echocardiography) and protein expression of markers for oxidative stress (HO-1),
      and inflammation (TNF-alpha, NLRP-3) were assessed. In adenine-fed rats,
      glibenclamide decreased BUN (controls: 6+/-0.6; adenine: 56.6+/-5.4;
      adenine+glibenclamide: 19.4+/-2.7 mmol/L), PCr (controls: 42+/-2.8; adenine:
      268+/-23; adenine+glibenclamide: 81+/-10 MUmol/L), proteinuria (controls: 150+/
      7.4; adenine: 303+/-19; adenine+glibenclamide: 220+/-13 MUmol/L) (all p<0.05).
      Glibenclamide decreased infiltration of chronic inflammatory cells, fibrosis,
      tubular damage and expression of HO-1, TNF-alpha and NLRP-3 in the kidney.
      Glibenclamide did not alter plasma uric acid concentrations (controls: 38+/-1;
      adenine: 63+/-4; adenine+glibenclamide: 69+/-14 MUmol/L). Cardiovascular changes
      included decreased systolic blood pressure and improved vascular responses
      although cardiac fibrosis, left ventricular stiffness and hypertrophy were not
      reduced. Glibenclamide improved kidney structure and function in CKD and
      decreased some cardiovascular parameters. Inflammatory markers and cell
      populations were attenuated by glibenclamide in kidneys.

PMID- 24291535
TI  - Energy intake and obesity: ingestive frequency outweighs portion size.
AB  - Energy intake is a function of the quantity of energy consumed per ingestive
      event and the number of these events. The marked increase of energy intake and
      body weight over the past 35 years indicates that there has been poor precision
      in the reciprocity of these two facets of intake. With recent study of the
      associations between gut "satiation" peptides and energy intake, there has been
      an emphasis on the contribution of portion size to positive energy balance.
      However, this orientation may not appropriately weight the contribution of
      ingestive frequency. Gut peptides are not purely satiation factors and metabolic
      and environmental cues may more strongly guide the onset and number of ingestive
      events. Evidence is presented that while both portion size and ingestive
      frequency have increased in the population, the latter may be more problematic
      for weight gain. The magnitude and time course of increments in ingestive
      frequency map better onto energy intake and BMI trends than changes of portion
      size. This may occur, in part, because dietary compensation and thermogenic
      effects are weaker for increases in ingestive frequency than portion size. Though
      not to the exclusion of consideration of portion size effects, improved weight
      management may be achieved with greater attention to the drivers of eating and
      drinking frequency.

PMID- 24291536
TI  - Short-term calorie restriction protects against renal senescence of aged rats by
      increasing autophagic activity and reducing oxidative damage.
AB  - To explore the effect of short-term calorie restriction (CR) on renal aging, 8
      week CR with 60% of the food intake of the ad libitum group was administered in
      25-month-old male Sprague-Dawley rats. Aged rats subjected to short-term CR had
      lower body weight, level of triglycerides and ratio of urine protein to urine
      creatinine, respectively. Short-term CR blunted the increased glomerular volume,
      the degree of fibrosis, p16 and the positive rate of senescence-associated beta
      galactosidase staining of the kidneys in old ad libitum group. Light chain 3/Atg8
      as an autophagy marker exhibited a marked decline in aged kidneys, which was
      increased by short-term CR. The levels of p62/SQSTM1 and polyubiquitin
      aggregates, which were increased in older kidneys, were blunted by short-term CR.
      Short-term CR retarded the level of 8-hydroxydeoxyguanosine, a marker of
      mitochondrial DNA oxidative damage. Moreover, we found an increased level of
      SIRT1 and AMPK, and a decreased level of mTOR in aged kidneys after short-term
      CR. These results suggested that short-term CR could be considered as a potential
      intervention for retardation of renal senescence by increasing autophagy and
      subsequently reducing oxidative damage. Three master regulators of energy
      metabolism, SIRT1, AMPK and mTOR are associated with these effects. 

PMID- 24291537
TI  - Coronaviruses in children with febrile neutropenia.

PMID- 24291532
TI  - Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials.
AB  - The brain vasculature has been increasingly recognized as a key player that
      directs brain development, regulates homeostasis, and contributes to pathological
      processes. Following ischemic stroke, the reduction of blood flow elicits a
      cascade of changes and leads to vascular remodeling. However, the temporal
      profile of vascular changes after stroke is not well understood. Growing evidence
      suggests that the early phase of cerebral blood volume (CBV) increase is likely
      due to the improvement in collateral flow, also known as arteriogenesis, whereas
      the late phase of CBV increase is attributed to the surge of angiogenesis.
      Arteriogenesis is triggered by shear fluid stress followed by activation of
      endothelium and inflammatory processes, while angiogenesis induces a number of
      pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The
      status of collaterals in acute stroke has been shown to have several prognostic
      implications, while the causal relationship between angiogenesis and improved
      functional recovery has yet to be established in patients. A number of
      interventions aimed at enhancing cerebral blood flow including increasing
      collateral recruitment are under clinical investigation. Transplantation of EPCs
      to improve angiogenesis is also underway. Knowledge in the underlying
      physiological mechanisms for improved arteriogenesis and angiogenesis shall lead
      to more effective therapies for ischemic stroke. 

PMID- 24291538
TI  - Examining the views of key stakeholders regarding the provision of occupational
      influenza vaccination for healthcare workers in Australia.
AB  - Annual vaccination of hospital healthcare workers (HCWs) may be an effective
      measure to reduce the transmission of healthcare associated influenza. However,
      vaccine coverage rates among HCWs in most public Australian hospitals are below
      satisfactory for a number of reasons. This study aimed to examine the opinions of
      key health stakeholders on current issues regarding HCW influenza vaccination. A
      qualitative study involving semi-structured interviews was undertaken with key
      Australian health stakeholders representing different organizations and sectors
      involved in influenza vaccination and policy. Amongst the participants, there was
      overwhelming support for HCW influenza vaccination. They viewed vaccination as
      one of the most important preventive measures for healthcare associated influenza
      and generally agreed that vaccination of HCWs reduces the overall risk of
      transmission to patients. However, there were contradictory attitudes regarding
      the evidence available for justifying the impact of vaccinating HCWs against
      influenza. Amongst the stakeholders interviewed, there was support for continuing
      to promote influenza vaccination for HCWs via the conventional framework.
      Participants recommended that hospitals continue to use conventional, voluntary
      strategies to increase vaccine coverage such as education and mobile carts. Given
      that the World Health Organization has included HCWs as a target group for
      influenza vaccination, Australian hospitals may need to start considering the use
      of mandatory policies in the near future. 

PMID- 24291539
TI  - Vaccination benefits and cost-sharing policy for non-institutionalized adult
      Medicaid enrollees in the United States.
AB  - Medicaid is the largest funding source of health services for the poorest people
      in the United States. Medicaid enrollees have greater health care, needs, and
      higher health risks than other individuals in the country and, experience
      disproportionately low rates of preventive care. Without, Medicaid coverage, poor
      uninsured adults may not be vaccinated or would, rely on publicly-funded programs
      that provide vaccinations. We examined each programs' policies related to benefit
      coverage and, copayments for adult enrollees. Our study was completed between
      October 2011 and September 2012 using a document review and a survey of Medicaid
      administrators that assessed coverage and cost-sharing policy for fee-for-service
      programs. Results were compared to a similar review, conducted in 2003. Over the
      past 10 years, Medicaid programs have typically maintained or expanded
      vaccination coverage benefits for adults and nearly half have explicitly
      prohibited copayments. The 17 programs that cover all recommended vaccines while
      prohibiting, copayments demonstrate a commitment to providing increased access to
      vaccinations for adult enrollees. When developing responses to fiscal and
      political challenges, the programs that do not cover all ACIP recommended adult
      vaccines or those that permit copayments for vaccinations, should consider all
      strategies to increase vaccinations and reduce costs to enrollees. 

PMID- 24291540
TI  - A dual vaccine candidate against norovirus and hepatitis E virus.
AB  - Norovirus (NoV) and hepatitis E virus (HEV) are both enterically-transmitted
      viruses causing gastroenteritis and hepatitis, respectively, in humans. While a
      vaccine against HEVs recently became available in China, there is no prophylactic
      or therapeutic approach against NoVs. Both NoV and HEV have surface protrusions
      formed by dimers of the protruding (P) domains of the viral capsids, which is
      responsible for virus-host interactions and eliciting viral neutralizing
      antibody. We developed in this study a bivalent vaccine against the two viruses
      through a recently developed polyvalent complex platform. The dimeric P domains
      of NoV and HEV were fused together, designated as NoV P(-)-HEV P, which was then
      linked with the dimeric glutathione-S-transferase (GST). After expression and
      purification in E. coli, the GST-NoV P(-)-HEV P fusion protein assembled into
      polyvalent complexes with a mean size of 1.8MUm, while the NoV P(-)-HEV P formed
      oligomers ranging from 100 to 420kDa. Mouse immunization study demonstrated that
      both GST-NoV P(-)-HEV P and NoV P(-)-HEV P complexes induced significantly higher
      antibody titers to NoV P(-) and HEV P, respectively, than those induced by a
      mixture of the NoV P(-) and HEV P dimers. Furthermore, the complex-induced
      antisera exhibited significantly higher neutralizing activity against HEV
      infection in HepG2/3A cells and higher blocking activity on NoV P particles
      binding to HBGA receptors than those of the dimer-induced antisera. Thus, GST-NoV
      P(-)-HEV P and NoV P(-)-HEV P complexes are promising dual vaccine candidates
      against both NoV and HEV. 

PMID- 24291541
TI  - What are the roles of calorie restriction and diet quality in promoting healthy
      longevity?
AB  - Epidemiological and experimental data indicate that diet plays a central role in
      the pathogenesis of many age-associated chronic diseases, and in the biology of
      aging itself. Data from several animal studies suggest that the degree and time
      of calorie restriction (CR) onset, the timing of food intake as well as diet
      composition, play major roles in promoting health and longevity, breaking the old
      dogma that only calorie intake is important in extending healthy lifespan. Data
      from human studies indicate that long-term CR with adequate intake of nutrients
      results in several metabolic adaptations that reduce the risk of developing type
      2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes
      the expected age-associated alterations in myocardial stiffness, autonomic
      function, and gene expression in the human skeletal muscle. However, it is
      possible that some of the beneficial effects on metabolic health are not entirely
      due to CR, but to the high quality diets consumed by the CR practitioners, as
      suggested by data collected in individuals consuming strict vegan diets. More
      studies are needed to understand the interactions among single nutrient
      modifications (e.g. protein/aminoacid, fatty acids, vitamins, phytochemicals, and
      minerals), the degree of CR and the frequency of food consumption in modulating
      anti-aging metabolic and molecular pathways, and in the prevention of age
      associated diseases. 

PMID- 24291542
TI  - Single-molecule enzymology based on the principle of the Millikan oil drop
      experiment.
AB  - The ability to monitor the progress of single-molecule enzyme reactions is often
      limited by the need to use fluorogenic substrates. A method based on the
      principle of the Millikan oil drop experiment was developed to monitor the change
      in charge of substrates bound to a nanoparticle and offers a means of detecting
      single-enzyme reactions without fluorescence detection. As a proof of principle
      of the ability to monitor reactions that result in a change in substrate charge,
      polymerization on a single DNA template was detected. A custom oligonucleotide
      was synthesized that allowed for the attachment of single DNA templates to gold
      nanoparticles with a single polymer tether. The nanoparticles were then tethered
      to the surface of a microfluidic channel where the positions of the
      nanoparticles, subjected to an oscillating electric field, were monitored using
      dark field microscopy. With short averaging times, the signal-to-noise level was
      low enough to discriminate changes in charge of less than 1.2%. Polymerization of
      a long DNA template demonstrated the ability to use the system to monitor single
      molecule enzymatic activity. Finally, nanoparticle surfaces were modified with
      thiolated moieties to reduce and/or shield the number of unproductive charges and
      allow for improved sensitivity. 

PMID- 24291544
TI  - Inflammation in intracerebral hemorrhage: from mechanisms to clinical
      translation.
AB  - Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes and is
      associated with high mortality and morbidity. Currently, no effective medical
      treatment is available to improve functional outcomes in patients with ICH.
      Potential therapies targeting secondary brain injury are arousing a great deal of
      interest in translational studies. Increasing evidence has shown that
      inflammation is the key contributor of ICH-induced secondary brain injury.
      Inflammation progresses in response to various stimuli produced after ICH.
      Hematoma components initiate inflammatory signaling via activation of microglia,
      subsequently releasing proinflammatory cytokines and chemokines to attract
      peripheral inflammatory infiltration. Hemoglobin (Hb), heme, and iron released
      after red blood cell lysis aggravate ICH-induced inflammatory injury. Danger
      associated molecular patterns such as high mobility group box 1 protein, released
      from damaged or dead cells, trigger inflammation in the late stage of ICH.
      Preclinical studies have identified inflammatory signaling pathways that are
      involved in microglial activation, leukocyte infiltration, toll-like receptor
      (TLR) activation, and danger associated molecular pattern regulation in ICH.
      Recent advances in understanding the pathogenesis of ICH-induced inflammatory
      injury have facilitated the identification of several novel therapeutic targets
      for the treatment of ICH. This review summarizes recent progress concerning the
      mechanisms underlying ICH-induced inflammation. We focus on the inflammatory
      signaling pathways involved in microglial activation and TLR signaling, and
      explore potential therapeutic interventions by targeting the removal of hematoma
      components and inhibition of TLR signaling. 

PMID- 24291543
TI  - Isolation of DNA using magnetic nanoparticles coated with dimercaptosuccinic
      acid.
AB  - Lately, the isolation of DNA using magnetic nanoparticles has received increased
      attention owing to their facile manipulation and low costs. Although methods
      involving their magnetic separation have been extensively studied, there is
      currently a need for an efficient technique to isolate DNA for highly sensitive
      diagnostic applications. We describe herein a method to isolate and purify DNA
      using biofunctionalized superparamagnetic nanoparticles synthesized by a modified
      polyol method to obtain the desired monodispersity, followed by surface
      modification with meso-2,3-dimercaptosuccinic acid (DMSA) containing carboxyl
      groups for DNA absorption. The DMSA-coated magnetic nanoparticles (DMSA-MNPs)
      were used for the isolation of DNA, with a maximum yield of 86.16%. In
      particular, we found that the isolation of DNA using small quantities of DMSA
      MNPs was much more efficient than that using commercial microbeads (NucliSENS
      easyMAG, BioMerieux). Moreover, the DMSA-MNPs were successfully employed in the
      isolation of genomic DNA from human blood. In addition, the resulting DNA
      nanoparticle complex was directly subjected to PCR amplification without prior
      elution, which could eventually lead to simple, rapid, sensitive and integrated
      diagnostic systems. 

PMID- 24291545
TI  - Building a neurocognitive profile of thought disorder in schizophrenia using a
      standardized test battery.
AB  - A core symptom of schizophrenia is thought disorder (TD). The cognitive abilities
      of semantic processing and executive function are argued to be etiologically
      linked to TD. However, there has been no comprehensive investigation of
      neurocognition in TD to date. The neurocognitive profile of 58 schizophrenia
      patients and 48 healthy controls was examined using the MATRICS Consensus
      Cognitive Battery and the D-KEFS Color-Word Interference Test. TD patients
      performed more poorly than non-TD patients on the cognitive domains of Verbal
      Learning and Inhibition, reflective of semantic and executive function
      respectively, confirming their critical roles over and above other cognitive
      deficits in schizophrenia. 

PMID- 24291546
TI  - Differential expression of SDF-1 isoforms in bladder cancer.
AB  - PURPOSE: SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known
      SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression
      has been detected in various malignancies, only few groups have reported
      differential expression of SDF-1 isoforms and its clinical significance. We
      evaluated the expression of 3 SDF-1 isoforms (alpha, beta and gamma) in bladder
      cancer. MATERIALS AND METHODS: Using quantitative polymerase chain reaction we
      measured SDF-1alpha, beta and gamma mRNA levels in 25 normal and 44 bladder
      cancer tissues, and in 210 urine specimens (28 normal, 74 benign, 57 bladder
      cancer, 35 bladder cancer history, 8 other cancer history and 8 other cancer)
      from consecutive patients. Levels were correlated with clinical outcome. RESULTS:
      Of the SDF-1 isoforms only SDF-1beta mRNA was significantly over expressed 2.5
      fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1alpha
      was expressed in bladder tissues but SDF-1gamma was undetectable. On multivariate
      analysis SDF-1beta was an independent predictor of metastasis and disease
      specific mortality (p=0.017 and 0.043, respectively). In exfoliated urothelial
      cells only SDF-1beta mRNA levels were differentially expressed with 91.2%
      sensitivity and 73.8% specificity for detecting bladder cancer. In patients with
      a bladder cancer history increased SDF-1beta levels indicated a 4.3-fold
      increased risk of recurrence within 6 months (p=0.0001). CONCLUSIONS: SDF-1
      isoforms are differentially expressed in bladder tissues and exfoliated
      urothelial cells. SDF-1beta mRNA levels in bladder cancer tissues predict a poor
      prognosis. Furthermore, SDF-1beta mRNA levels in exfoliated cells detect bladder
      cancer with high sensitivity and they are a potential predictor of future
      recurrence.

PMID- 24291547
TI  - The association between statin medication and progression after surgery for
      localized renal cell carcinoma.
AB  - PURPOSE: Evidence suggests that statins may influence pathways of renal cell
      carcinoma proliferation, although to our knowledge no study has examined the
      influence of statin medications on the progression of renal cell carcinoma in
      humans. MATERIALS AND METHODS: We identified 2,608 patients with localized renal
      cell carcinoma who were treated surgically between 1995 and 2010 at our tertiary
      referral center. Competing risks Cox proportional hazards models were used to
      evaluate the relationship between statin use and time to local recurrence or
      progression (metastases or death from renal cell carcinoma) and overall survival.
      Statin use was modeled as a time dependent covariate as a sensitivity analysis.
      Models were adjusted for clinical and demographic features. RESULTS: Of 2,608
      patients 699 (27%) were statin users at surgery. Statin users had similar
      pathological characteristics compared to nonusers. At a median followup of 36
      months there were 247 progression events. Statin use was associated with a 33%
      reduction in the risk of progression after surgery (HR 0.67, 95% CI 0.47-0.96, p
      = 0.028) and an 11% reduction in overall mortality that was not significant (HR
      0.89, 95% CI 0.71-1.13, p = 0.3). Modeling statin use as a time dependent
      covariate attenuated the risk reduction in progression to 23% (HR 0.77, p = 0.12)
      and augmented the risk reduction in overall survival (HR 0.71, p = 0.002).
      CONCLUSIONS: In our cohort statin use was associated with a reduced risk of
      progression and overall mortality, although this effect was sensitive to the
      method of analysis. If validated in other cohorts, this finding warrants
      consideration of prospective research on statins in the adjuvant setting.

PMID- 24291549
TI  - Reply to Acute decompensated heart failure and pulmonary hypertension.

PMID- 24291550
TI  - Acute decompensated heart failure and pulmonary hypertension.

PMID- 24291548
TI  - Dysregulation of beta-catenin is an independent predictor of oncologic outcomes
      in patients with clear cell renal cell carcinoma.
AB  - PURPOSE: Epithelial-to-mesenchymal transition is thought to have a crucial role
      in cancer progression and metastatic egress. We evaluated the association of beta
      catenin, an important mediator of epithelial-to-mesenchymal transition, with
      pathological parameters and oncologic outcomes in patients with clear cell renal
      cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining was performed
      for beta-catenin on tissue microarrays of patients with nonmetastatic clear cell
      renal cell carcinoma. Membranous and cytoplasmic expression patterns were
      assessed separately. beta-Catenin was considered dysregulated if membranous as
      well as cytoplasmic expression was abnormal. Groups were compared based on normal
      vs dysregulated beta-catenin. Survival probabilities were assessed by the Kaplan
      Meier method. Cox proportional hazard models were used to identify predictors of
      oncologic outcomes. RESULTS: Included in the study were 406 patients with a
      median followup of 58 months. Of the patients 52 (12.8%) and 25 (6.2%)
      experienced recurrence and died of clear cell renal cell carcinoma, respectively.
      beta-Catenin was dysregulated in 70 patients (17.2%). Dysregulation was uniformly
      associated with adverse pathological features, including advanced T stage, larger
      tumor diameter, nodal positivity, higher Fuhrman grade, tumor thrombus,
      sarcomatoid features, necrosis and lymphovascular invasion (each p<0.001).
      Patients with dysregulated beta-catenin had inferior recurrence-free and cancer
      specific survival (each p<0.001). On multivariate analysis adjusting for tumor
      stage, nodal status and grade dysregulation was an independent predictor of
      recurrence-free and cancer specific survival (HR 2.2, 95% CI 1.2-3.9, p=0.008 and
      HR 2.4, 95% CI 1.1-5.6, p=0.044, respectively). CONCLUSIONS: Dysregulation of
      beta-catenin may be an important phenomenon in clear cell renal cell carcinoma
      carcinogenesis. These findings support further study of beta-catenin, and
      systematic assessment of beta-catenin and epithelial-to-mesenchymal transition in
      clear cell renal cell carcinoma.

PMID- 24291551
TI  - The isolation and molecular characterization of Leishmania spp. from patients
      with American tegumentary leishmaniasis in northwest Argentina.
AB  - American tegumentary leishmaniasis (ATL) is a group of zoonotic diseases caused
      by kinetoplastid flagellates of the genus Leishmania. A total of 66 patients
      diagnosed as positive ATL cases from northwest Argentina were included in this
      study. Leishmania stocks were isolated in vitro and analyzed over promastigote
      cultures sown on FTA through nested PCR and sequence of cytochrome b (cyt b). The
      molecular analysis resulted in the incrimination of L. (Viannia) braziliensis as
      the predominant species in the studied area, identifying two genotypes of L. (V.)
      braziliensis, 24 cases of Ab-1 cyt b and 41 cases of Ab-2 cyt b. One L. (V.)
      guyanensis strain was obtained from a traveler from the Brazilian Amazon. The
      prevalence of different genotypes was in agreement with previous studies,
      suggesting the necessity for new systems to study the genetic diversity in more
      detail. Most of the cases typified in this study were registered in the area of
      Zenta Valley (Oran, Hipolito Yrigoyen, and Pichanal cities), pointing a link
      between genotype and geographical origin of the sample. Sex and age distribution
      of the patients indicate that the transmission was predominantly associated with
      rural areas or rural activities, although the results might not exclude the
      possibility of peri-urban transmission. This work represents, so far, the largest
      isolation and molecular characterization of ATL cases in Argentina. 

PMID- 24291552
TI  - Inhibition of KCa3.1 suppresses TGF-beta1 induced MCP-1 expression in human
      proximal tubular cells through Smad3, p38 and ERK1/2 signaling pathways.
AB  - It is well known that TGF-beta1 plays a central role in renal fibrosis due in
      large part to stimulation of inflammatory responses. KCa3.1, a potassium channel
      protein, has been suggested as a potential therapeutic target for diseases such
      as sickle cell anemia, autoimmunity, atherosclerosis and more recently, kidney
      fibrosis. Blockade of KCa3.1 has been shown to ameliorate renal fibrosis in
      diabetic mice in association with reduced TGF-beta1 signaling. However, the
      centrality of KCa3.1 activation to TGF-beta1 induced inflammation remains
      unknown. In this study, human proximal tubular cells (HK2 cells) were incubated
      with TGF-beta1 (2 ng/ml) for 48 h in the presence or absence of KCa3.1 siRNA or
      the KCa3.1 inhibitor TRAM34. HK2 cells overexpressing KCa3.1 were studied in
      parallel. The mRNA and protein expression of monocyte chemoattractant protein-1
      (MCP-1) were measured by qRT-PCR and ELISA. Downstream TGF-beta1 signaling
      molecules Smad3, p38 and ERK1/2 were measured by Western blot analysis. Using
      whole-cell patch clamp techniques we found that TGFbeta-1 induced a large KCa3.1
      K-current that was inhibited by TRAM34. TGF-beta1 also increased MCP-1 mRNA and
      protein expression in HK2 cells compared to control, an effect that was reversed
      by in the presence of KCa3.1 siRNA. Similarly, TRAM34 significantly reduced the
      TGF-beta1-mediated increase in MCP-1 at both the mRNA and protein levels.
      Inhibition of KCa3.1 with KCa3.1 siRNA or TRAM34 also reduced TGF-beta1-induced
      phosphorylation of Smad3, p38 and ERK1/2 MAPK pathways. Conversely overexpression
      of KCa3.1 induced TGF-beta1 signaling cascades and expression of MCP-1. The
      present study is consistent with a key role for KCa3.1 renal proximal tubular
      cells in mediating the TGF-beta1 induction of MCP-1 expression in HK2 cells via
      Smad3, p38 and ERK1/2 MAPK signaling pathways.

PMID- 24291553
TI  - Dose-to-dose variations with single packages of counterfeit medicines and
      adulterated dietary supplements as a potential source of false negatives and
      inaccurate health risk assessments.
AB  - In this report, we show three examples of how the variability in dose units in
      single packages of counterfeit medicines and adulterated dietary supplements may
      contribute to a false negative screening result and inaccurate health risk
      assessments. We describe a counterfeit Viagra 100mg blister pack and a box of an
      instant coffee both containing dose units with and without an active
      pharmaceutical ingredient (API). We also describe a purportedly herbal slimming
      product with capsules that mutually differed in API and impurities. The
      adulterated dietary supplements contained sibutramine, benzyl-sibutramine, N
      desmethyl-sibutramine (DMS), N,N-didesmethyl-sibutramine (DDMS) and several other
      related impurities. Counterfeit medicines and adulterated dietary supplements are
      a health risk because their quality is unreliable. Health risks are even greater
      when such unreliability extends to fundamental differences between dose units in
      one package. Because dose-to-dose variability for these products is
      unpredictable, the confidence interval of a sample size is unknown. Consequently,
      the analyses of a selection of dose units may not be representative for the
      package. In the worst case, counterfeit or unauthorised medicines are not
      recognised as such or a health risk is not identified. In order to reduce
      erroneous results particular care should be taken when analysing a composite of
      dose units, when finding no API in a dietary supplement and when finding
      conformity in a suspect counterfeit medicine. 

PMID- 24291554
TI  - Uptake of perfluorinated compounds by plants grown in nutrient solution.
AB  - The uptake rates of three perfluorinated carboxylates and three perfluorinated
      sufonates by a grass (B diandrus) grown in nutrient solution at two different
      perfluorinated compounds (PFCs) concentrations were assessed. Grass can be
      ingested by grazing animals causing the PFCs to enter the food chain, which is a
      pathway of human exposure to these compounds. A rapid and miniaturized method was
      developed to determine PFCs in plants, based on a matrix solid-phase dispersion
      (MSPD) extraction procedure followed by quantitation by HPLC-MS/MS with an MQL in
      the range from 1 to 9 ng/g. An increase of PFCs levels in plant was observed
      along the exposure time. Differences in uptake for studied perfluorinated
      carboxylates were found, showing a decrease with carbon chain length (from 3027
      to 1,167 ng/g at the end of assay), whereas no significant differences in
      absorption were obtained between perfluorinated sulfonates (about 1,700 ng/g).
      Initially, higher PFC transfer factors (ratio between concentration in plant and
      concentration in initial nutrient solution) were obtained for plants growing in
      the nutrient solution at the highest PFC concentration, but these factors became
      similar with time to plants exposed to the lowest concentration.

PMID- 24291555
TI  - Experimental study on the nitrogen dioxide and particulate matter emissions from
      diesel engine retrofitted with particulate oxidation catalyst.
AB  - A particulate oxidation catalyst (POC) was employed to perform experiments on the
      engine test bench to evaluate the effects on the nitrogen dioxide (NO2) and
      particulate matter (PM) emissions from diesel engine. The engine exhaust was
      sampled from both upstream and downstream of the POC. The results showed that the
      POC increased the ratios of NO2/NOx significantly in the middle and high loads,
      the ratio of NO2/nitrogen oxides (NOx) increased 4.5 times on average under all
      experiment modes with the POC. An engine exhaust particle sizer (EEPS) was used
      to study the particle number-weighted size distributions and the abnormal
      particle emissions with the POC. The results indicated that the average reduction
      rate of particle number (PN) was 61% in the operating range of the diesel engine.
      At the engine speed of 1,400 r/min, the reduction rates of PN tended to decrease
      with the larger particle size. In the long time run under the steady mode (520
      Nm, 1,200 r/min), abnormal particle emissions after the POC happened seven times
      in the first hour, and the average PN concentration of these abnormal emission
      peaks was much higher than that in normal state. The particle emissions of peaks
      1-5 equaled the particles emitted downstream of the POC in normal state for 1.9h
      in number concentration, and for 3.6h in mass concentration. The PN
      concentrations tended to increase over time in 5h under the steady engine mode
      and the increase of the PN in the size range of 6.04-14.3 nm was more evident.

PMID- 24291556
TI  - Polybrominated diphenyl ethers and multiple stressors influence the reproduction
      of free-ranging tree swallows (Tachycineta bicolor) nesting at wastewater
      treatment plants.
AB  - Reproductive success of birds is influenced by maternal factors, ambient
      temperatures, predation, food supply, and/or exposure to environmental
      contaminants e.g., flame retardants (FRs). Reproduction of tree swallows
      (Tachycineta bicolor) was compared among waste water treatment plants (WWTPs) and
      a reference reservoir in Ontario, Canada (2007-2010), to determine the importance
      of exposure to polybrominated diphenyl ether (PBDEs) FRs within a complex
      contaminant cocktail, relative to natural and biological factors known to
      influence avian reproduction. The birds primarily consumed insects emerging from
      the reference reservoir and WWTP outflows, where effluent mixed with receiving
      waters. FR egg concentrations were dominated by 5 PBDE congeners (?5PBDEs):
      2,2'.4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4'-tetrabromodiphenyl ether
      (BDE-47), 2,2'4,4',6-pentabromodiphenyl ether (BDE-100), 2,2',4,4',5,5'
      hexabromodiphenyl ether (BDE-153), and 2,2',4,4',5,6'-hexabromodiphenyl ether
      (BDE-154), with much lower concentrations of decabromodiphenylether (BDE-209),
      hexabromocyclododecane (HBCDD), and novel FRs. Although higher than ?5PBDEs,
      polychlorinated biphenyls (PCBs) egg concentrations were unlikely to affect the
      swallows' reproduction. Clutch size and timing, fledging, breeding success, and
      predation, varied significantly among sites, generally being poorer at WWTP1 and
      better at WWTP2. The early reproductive stages were sensitive to some FRs at
      measured concentrations. The ?5PBDEs, maternal age, and minimum ambient
      temperatures predicted onset of egg laying in the most parsimonious statistical
      model, and there were positive relationships between egg size and HBCDD or BDE
      209 concentrations. However, there were no significant correlations with any
      reproductive measures, individual BDE congeners or low concentrations of novel
      FRs, in this first such report for novel FRs and wild birds. Tree swallows are
      passerines, and passerines may differ from birds of prey in their reproductive
      sensitivity to PBDE exposure: lay date, minimum temperatures, and predation, but
      not PBDE exposure, predicted reproductive productivity. Overall, there was some
      influence of the PBDEs available in these WWTP outflows on early reproductive
      parameters, but not reproductive output, of these passerines. 

PMID- 24291557
TI  - Trends in serum cotinine concentrations among daily cigarette smokers: data from
      NHANES 1999-2010.
AB  - To the best of our knowledge, there have been no apparent studies of the trends
      in serum cotinine levels among smokers. Data from National Health and Nutrition
      Examination Survey for the period 1999-2010 were used to evaluate trends for
      serum cotinine levels; average number of cigarettes smoked per day; and Cambridge
      filter method (CFM) tar and CFM nicotine levels by gender, race/ethnicity, and
      cigarette mentholation status. Regression models were fitted to evaluate the
      factors associated with serum cotinine levels. Serum cotinine levels increased
      over time for both males and females, non-Hispanic whites and others. CFM
      nicotine levels also rose over time for cigarettes smoked by both males and
      females and by both non-Hispanic whites and non-Hispanic blacks. Average number
      of cigarettes smoked per day decreased over time for females, non-Hispanic whites
      and non-Hispanic blacks. CFM tar levels fell only for Mexican Americans. Exposure
      to second hand smoke at home was found to be associated with more than 1 ng/ml
      increase in serum cotinine levels. This large study on a nationally
      representative sample of daily smokers suggested that increasing concentrations
      of CFM nicotine in cigarettes over time led to elevated serum cotinine levels
      even though the number of cigarettes smoked daily remained relatively constant.

PMID- 24291558
TI  - Does microbial centimeter-scale heterogeneity impact MCPA degradation in and
      leaching from a loamy agricultural soil?
AB  - The potential for pesticide degradation varies greatly at the centimeter-scale in
      agricultural soil. Three dimensional numerical simulations were conducted to
      evaluate how such small-scale spatial heterogeneity may affect the leaching of
      the biodegradable pesticide 2-methyl-4-chlorophenoxyacetic acid (MCPA) in the
      upper meter of a variably-saturated, loamy soil profile. To incorporate realistic
      spatial variation in degradation potential, we used data from a site where 420
      mineralization curves over 5 depths have been measured. Monod kinetics was fitted
      to the individual curves to derive initial degrader biomass values, which were
      incorporated in a reactive transport model to simulate heterogeneous
      biodegradation. Six scenarios were set up using COMSOL Multiphysics to evaluate
      the difference between models having different degrader biomass distributions
      (homogeneous, heterogeneous, or no biomass) and either matrix flow or
      preferential flow through a soil matrix with a wormhole. MCPA leached, within 250
      days, below 1m only when degrader biomass was absent and preferential flow
      occurred. Both biodegradation in the plow layer and the microbially active lining
      of the wormhole contributed to reducing MCPA-leaching below 1m. The spatial
      distribution of initial degrader biomass within each soil matrix layer, however,
      had little effect on the overall MCPA-leaching.

PMID- 24291559
TI  - Chemical weathering and CO2 consumption in the Lower Mekong River.
AB  - Data on river water quality from 42 monitoring stations in the Lower Mekong Basin
      obtained during the period 1972-1996 was used to relate solute fluxes with
      controlling factors such as chemical weathering processes. The total dissolved
      solid (TDS) concentration of the Lower Mekong varied from 53 mg/L to 198 mg/L,
      and the median (114 mg/L) was compared to the world spatial median value (127
      mg/L). Total cationic exchange capacity (Tz(+)) ranged from 729 to 2,607
      MUmolc/L, and the mean (1,572 MUmolc/L) was 1.4 times higher than the world
      discharge-weighted average. Calcium and bicarbonate dominated the annual ionic
      composition, accounting for ~70% of the solute load that equalled 41.2*10(9)kg/y.
      TDS and major elements varied seasonally and in a predictable way with river
      runoff. The chemical weathering rate of 37.7t/(km(2)y), with respective carbonate
      and silicate weathering rates of 27.5t/(km(2) y) (13.8mm/ky) and 10.2t/(km(2) y)
      (3.8mm/ky), was 1.5 times higher than the global average. The CO2 consumption
      rate was estimated at 191*10(3)molCO2/(km(2)y) for silicate weathering, and
      286*10(3)molCO2/(km(2)y) by carbonate weathering. In total, the Mekong basin
      consumed 228*10(9)molCO2/y and 152*10(9)molCO2/y by the combined weathering of
      carbonate and silicate, constituting 1.85% of the global CO2 consumption by
      carbonate weathering and 1.75% by silicates. This is marginally higher than its
      contribution to global water discharge ~1.3% and much higher than (more than
      three-fold) its contribution to world land surface area. Remarkable CO2 consumed
      by chemical weathering (380*10(9)mol/y) was similar in magnitude to dissolved
      inorganic carbon as HCO3(-) (370*10(9)mol/y) exported by the Mekong to the South
      China Sea. In this landscape, atmospheric CO2 consumption by rock chemical
      weathering represents an important carbon sink with runoff and physical erosion
      controlling chemical erosion.

PMID- 24291560
TI  - Ketoprofen removal by O3 and O3/UV processes: kinetics, transformation products
      and ecotoxicity.
AB  - Ozonation (O3) and its combination with ultraviolet radiation (O3/UV) were used
      to decompose ketoprofen (KET). Depending on the initial KET concentration,
      fourteen to fifty time's faster KET degradation was achieved using combined O3/UV
      method compared to simple ozonation. Using both methods, formation of four major
      aromatic transformation products were observed: 3-(1-hydroxyethyl)benzophenone, 3
      (1-hydroperoxyethyl) benzophenone, 1-(3-benzoylphenyl) ethanone and 3
      ethylbenzophenone. In the combined treatment the degradation was mainly due to
      the direct effect of UV light, however, towards the end of the treatment, O3
      highly contributed to the mineralization of small carboxylic acids. High (~90%)
      mineralization degree was achieved using the O3/UV method. Toxicity tests
      performed using representatives of three trophic levels of the aquatic ecosystems
      (producers, consumers and decomposers) Pseudokirchneriella subcapitata green
      algae, Daphnia magna zooplanktons and Vibrio fischeri bacteria showed that under
      the used experimental conditions the transformation products have significantly
      higher toxicity towards all the test organisms, than KET itself. The bacteria and
      the zooplanktons showed higher tolerance to the formed products than algae. The
      measured toxicity correlates well with the concentration of the aromatic
      transformation products, therefore longer treatments than needed for complete
      degradation of KET are strongly suggested, in order to avoid possible impact of
      aromatic transformation products on the aquatic ecosystem. 

PMID- 24291561
TI  - Iron oxides stimulate microbial monochlorobenzene in situ transformation in
      constructed wetlands and laboratory systems.
AB  - Natural wetlands are transition zones between anoxic ground and oxic surface
      water which may enhance the (bio)transformation potential for recalcitrant chloro
      organic contaminants due to the unique geochemical conditions and gradients.
      Monochlorobenzene (MCB) is a frequently detected groundwater contaminant which is
      toxic and was thought to be persistent under anoxic conditions. Furthermore, to
      date, no degradation pathways for anoxic MCB removal have been proven in the
      field. Hence, it is important to investigate MCB biodegradation in the
      environment, as groundwater is an important drinking water source in many
      European countries. Therefore, two pilot-scale horizontal subsurface-flow
      constructed wetlands, planted and unplanted, were used to investigate the
      processes in situ contributing to the biotransformation of MCB in these gradient
      systems. The wetlands were fed with anoxic MCB-contaminated groundwater from a
      nearby aquifer in Bitterfeld, Germany. An overall MCB removal was observed in
      both wetlands, whereas just 10% of the original MCB inflow concentration was
      detected in the ponds. In particular in the gravel bed of the planted wetland,
      MCB removal was highest in summer season with 73 +/- 9% compared to the unplanted
      one with 40 +/- 5%. Whereas the MCB concentrations rapidly decreased in the
      transition zone of unplanted gravel to the pond, a significant MCB removal was
      already determined in the anoxic gravel bed of the planted system. The
      investigation of hydro-geochemical parameters revealed that iron and sulphate
      reduction were relevant redox processes in both wetlands. In parallel, the
      addition of ferric iron or nitrate stimulated the mineralisation of MCB in
      laboratory microcosms with anoxic groundwater from the same source, indicating
      that the potential for anaerobic microbial degradation of MCB is present at the
      field site.

PMID- 24291562
TI  - Organochlorine concentrations (PCBs, DDTs, HCHs, HCB and MIREX) in delphinids
      stranded at the northeastern Brazil.
AB  - Organochlorine compounds are highly persistent in the environment, causing
      bioaccumulation and biomagnification through the marine food chain. To verify the
      bioaccumulation pattern of DDT and its metabolites, as well as PCBs, Mirex, HCHs
      and HCB, samples of subcutaneous adipose tissue from 25 Guiana dolphins (Sotalia
      guianensis), two Fraser's dolphins (Lagenodelphis hosei), two spinner dolphins
      (Stenella longirostris), one spotted dolphin (Stenella frontalis), and one
      striped dolphin (Stenella coeruleoalba) were analyzed. The collected specimens
      were found stranded in northeastern Brazil between 2005 and 2011. The
      concentrations were reported in MUg.g(-1) lip, varying from 0.02 to 17.3 for
      SigmaPCB, from 0.003 to 5.19 for SigmaDDT, from 0.005 to 0.16 for SigmaHCH, from
      0.002 to 0.16 for HCB, and from 0.02 to 2.38 for Mirex. The PCBs dominated the
      bioaccumulation pattern for both the Guiana and spinner dolphins; for the other
      species, DDT was the major compound. A discriminant function analysis revealed
      the differences in the organochlorine accumulation patterns between the Guiana
      dolphin (S. guianensis) and the continental shelf/oceanic dolphins (S. frontalis
      and S. longirostris). The results also show that the concentrations of
      organochlorine compounds found in the delphinids in northeastern Brazil were
      lower than the delphinids found in other regions of Brazil, as well as other
      locations worldwide with intense agroindustrial development and/or a larger
      population. 

PMID- 24291563
TI  - Status, distribution and ecological risk of organochlorines (OCs) in the surface
      sediments from the Ravi River, Pakistan.
AB  - Organochlorines (OCs) including organochlorine pesticides (OCPs) and
      polychlorinated biphenyl (PCBs) were analyzed in surface sediments from the Ravi
      River, Punjab, Pakistan. Among the OCPs, hexachlorocyclohexane (HCHs),
      dichlorodiphenyltrichloroethane (DDTs) and chlordane (cis- and trans-) were most
      abundant and their concentrations were ranged from n.d to 16.0 ng g(-1), 1.5 to
      58.5 ng g(-1) and n.d to 29.0 ng g(-1), respectively. Concentrations of
      Sigma31PCBs ranged from 4.6 to 424.3 ng g(-1) with a mean value of 48.9 ng g(-1).
      In general, the concentrations of all studied organochlorines (OCs) in sediments
      collected from the sampling sites in the vicinity of industrial areas were higher
      than those from the agricultural areas. Compositional analyses of PCBs indicated
      that penta- and tetra-PCBs homologues were dominant which was consistent with the
      previous studies. Compared with other areas around the world, levels of OCs in
      sediments from the Ravi River were within the range, but were found to be much
      higher than previously reported from Pakistan. According to established sediment
      quality guidelines (SQGs), screening-level risk assessment of OCPs and PCBs
      suggested that they have a potential for adverse effects on benthic organisms.

PMID- 24291565
TI  - Increasing working memory capacity with theta transcranial alternating current
      stimulation (tACS).
AB  - The study aimed to investigate the influence of transcranial alternating current
      stimulation (tACS) on working memory's (WM) storage capacity. Sham/verum tACS
      with individually determined theta frequency was applied to the left parietal
      (target electrode=P3) or frontal (target electrode=F3) brain areas (return
      electrode above the right eyebrow). After sham and verum stimulation, 24
      respondents solved a task measuring the scope of attention while their
      electroencephalogram (EEG) was recorded. Verum tACS with the target electrode
      positioned over the left parietal brain area significantly increased WM storage
      capacity, as compared to sham tACS. No such influence was observed for tACS with
      the target electrode positioned over the left frontal area. Increased WM storage
      capacity was accompanied by event-related potential (ERP) P300 latency decrease
      in the left hemisphere. The obtained behavioral and neuroelectric data emphasize
      the causal relationship between WM storage capacity and theta frequency
      oscillations in the left parietal brain area. 

PMID- 24291566
TI  - Now you see it, now you don't: a biochemist's primer for advances in high
      resolution microscopy: comment on "Biomolecular dynamics and binding studies in
      the living cell" by Stephan Diekmann and Christian Hoischen.

PMID- 24291564
TI  - Triclocarban, triclosan and its transformation product methyl triclosan in native
      earthworm species four years after a commercial-scale biosolids application.
AB  - Triclocarban (TCC), triclosan (TCS) and methyl triclosan (Me-TCS) were detected
      in soil and the native population of earthworms of an agricultural field in
      Ottawa, Canada, about four years after a commercial-scale application of
      biosolids. In soil that received biosolids, TCC and TCS were detected at median
      concentrations of 13.0 and 1.5 ng/g soil (d.w.), respectively, while Me-TCS, the
      transformation product of triclosan, was detected at a six-fold higher median
      concentration than its precursor. In earthworms collected at the biosolids
      amended field-plot about four years post application, Me-TCS was also detected at
      higher concentrations (26 to 114 ng/g tissue d.w.) than TCS (16-51 ng/g) and TCC
      (4-53 ng/g). These data provide evidence that not only parent compounds but also
      their transformation products need to be considered in faunal bioaccumulation
      studies. Moreover, the preliminary results for pooled earthworm samples from
      different ecological groups suggest that the degree of bioaccumulation of
      biosolids-associated contaminants may depend on the habitat and feeding behavior
      of the organisms.

PMID- 24291567
TI  - Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series
      N-substituted N'-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines
      and their inhibition of human cytosolic isozymes I and II and the transmembrane
      tumor-associated isozymes IX and XII.
AB  - A series of novel N-substituted N'-(2-arylmethylthio-4-chloro-5
      methylbenzenesulfonyl)guanidines 9-41 have been synthesized and investigated as
      inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1),
      that is the cytosolic CA I and II, and cancer-associated isozymes CA IX and XII.
      Against the human CA I investigated compounds showed KI in the range of 87-6506
      nM, toward hCA II ranging from 7.8 to 4500 nM, against hCA IX in the range of 4.7
      416 nM and against hCA XII at range of 0.96-540 nM. Compounds 10, 12-14, 16, 18
      20, 24-26, 31 and 32 exhibited a powerful inhibitory potency toward hCA IX (K(I)
      = 4.7-21 nM) in comparison to the reference sulfonamides AAZ, MZA, EZA, DCP and
      IND (K(I) = 24-50 nM). Compound 14 was the most potent inhibitor of hCA I (K(I) =
      87 nM), hCA IX (K(I) = 4.7 nM) and hCA XII (K(I) = 0.96 nM), while 26 was the
      most effective inhibitor of hCA II (K(I) = 7.8 nM). The most promising compound
      32 exerted the highest selectivity ratios toward hCA IX versus hCA I (hCA I/hCA
      IX = 261) and hCA II (hCA II/hCA IX = 26). The in vitro antitumor activity of
      compounds 10, 13, 14, 21, 22, 25, 32, 38 and 41 was evaluated at the US National
      Cancer Institute (NCI) against a panel of 60 human tumor cell lines. The most
      active antitumor agents 21 and 25, inhibiting 32-35 human tumor cell lines with
      GI50 in the range of 2.1-5.0 MUM also showed relatively high inhibitory activity
      toward hCA IX and XII with KI from 18 to 40 nM.

PMID- 24291568
TI  - Synthesis and biological evaluation of alpha-triazolyl chalcones as a new type of
      potential antimicrobial agents and their interaction with calf thymus DNA and
      human serum albumin.
AB  - A series of alpha-triazolyl chalcones were efficiently synthesized. Most of the
      prepared compounds showed effective antibacterial and antifungal activities.
      Noticeably, alpha-triazolyl derivative 9a exhibited low MIC value of 4 MUg/mL
      against MRSA and Micrococcus luteus, which was comparable or even superior to
      reference drugs. The further research revealed that compound 9a could effectively
      intercalate into Calf Thymus DNA to form 9a-DNA complex which might block DNA
      replication to exert their powerful antimicrobial activities. Competitive
      interactions between 9a and metal ions to Human Serum Albumin (HSA) suggested the
      participation of Fe(3+), K(+) and Mg(2+) ions in 9a-HSA system could increase the
      concentration of free 9a, shorten its storage time and half-life in the blood,
      thus improving its antimicrobial efficacy.

PMID- 24291569
TI  - Thermodynamics of imidazole-ligand binding to Ni-nitrilotriacetate in solution
      and covalently attached to agarose beads: imidazole, his-6 (his-tag) peptide and
      a new bis-imidazolo-dithiane.
AB  - A new imidazolo- and thiol-containing ligand is prepared and characterized with
      the intent to serve as surrogate and mimic for the canonical ligands imidazole
      and hexa-histidinyl peptide (his-6) in immobilized metal affinity chromatography
      (IMAC) [1,2] systems. The affinity of this ligand: 1,8 bis (N1,N1')imidazolo-octa
      (3,6)-dithiane or bImOdS, to Ni-nitrilotriacetic acid (Ni-NTA) complex in
      solution is measured and compared with that of imidazole and his-6 peptide via
      isothermal titration calorimetry (ITC). In addition, bImOdS is compared with his
      6 binding to the solid-state matrix of Ni-NTA-charged agarose beads, as employed
      routinely in IMAC. Results reported here include the following: (1) two imidazole
      moieties bind within a single Ni-NTA complex, while bImOds, being an imidazolo
      dimer, binds with 1:1, and his-6 peptide binds with 1:3 stoichiometry. (2)
      Enthalpies of reaction for imidazole and his-6 peptide are reported - these can
      be utilized to predict changes in affinity in IMAC systems with temperature,
      should protein unfolding/refolding steps in purification be desired at alternate
      temperatures. (3) Metal analyses of the Ni-NTA agarose beads suggests that ~2/3
      of the nickel is present in low-affinity sites, which will complicate protein
      separations at high protein-concentration loading. An improved procedure for
      subtracting ligand dilution heats from ITC analyses is presented in an Appendix. 

PMID- 24291570
TI  - The value of colonoscopy.

PMID- 24291571
TI  - DNA methyltransferase activity is required for memory-related neural plasticity
      in the lateral amygdala.
AB  - We have previously shown that auditory Pavlovian fear conditioning is associated
      with an increase in DNA methyltransferase (DNMT) expression in the lateral
      amygdala (LA) and that intra-LA infusion or bath application of an inhibitor of
      DNMT activity impairs the consolidation of an auditory fear memory and long-term
      potentiation (LTP) at thalamic and cortical inputs to the LA, in vitro. In the
      present study, we use awake behaving neurophysiological techniques to examine the
      role of DNMT activity in memory-related neurophysiological changes accompanying
      fear memory consolidation and reconsolidation in the LA, in vivo. We show that
      auditory fear conditioning results in a training-related enhancement in the
      amplitude of short-latency auditory-evoked field potentials (AEFPs) in the LA.
      Intra-LA infusion of a DNMT inhibitor impairs both fear memory consolidation and,
      in parallel, the consolidation of training-related neural plasticity in the LA;
      that is, short-term memory (STM) and short-term training-related increases in
      AEFP amplitude in the LA are intact, while long-term memory (LTM) and long-term
      retention of training-related increases in AEFP amplitudes are impaired. In
      separate experiments, we show that intra-LA infusion of a DNMT inhibitor
      following retrieval of an auditory fear memory has no effect on post-retrieval
      STM or short-term retention of training-related changes in AEFP amplitude in the
      LA, but significantly impairs both post-retrieval LTM and long-term retention of
      AEFP amplitude changes in the LA. These findings are the first to demonstrate the
      necessity of DNMT activity in the consolidation and reconsolidation of memory
      associated neural plasticity, in vivo. 

PMID- 24291572
TI  - The roles of the nucleus accumbens core, dorsomedial striatum, and dorsolateral
      striatum in learning: performance and extinction of Pavlovian fear-conditioned
      responses and instrumental avoidance responses.
AB  - This study examined the effects of bilateral excitotoxic lesions of the nucleus
      accumbens core (NAc-co), dorsomedial striatum (DMS) or dorsolateral striatum
      (DLS) of rats on the learning and extinction of Pavlovian and instrumental
      components of conditioned avoidance responses (CARs). None of the lesions caused
      sensorimotor deficits that could affect locomotion. Lesions of the NAc-co, but
      not DMS or DLS, decreased unconditioned and conditioned freezing. The NAc-co and
      DLS lesioned rats learned the 2-way active avoidance task more slowly. These
      results suggest: (i) CARs depend on both Pavlovian and instrumental learning;
      (ii) learning the Pavlovian component of CARs depends on the NAc-co; learning the
      instrumental component of CARs depends on the DLS, NAc and DMS; (iii) although
      the NAc-co is also needed for learning the instrumental component, it is not
      clear whether it plays a role in learning the instrumental component per se or if
      it simply allows learning of the Pavlovian component which is a pre-condition for
      learning the instrumental component; (iv) we did not find evidence that the DMS
      and DLS play the same roles in habit and goal-directed aspects of the
      instrumental component of CARs as observed in appetitive motivated instrumental
      responding. 

PMID- 24291573
TI  - Human brainstem plasticity: the interaction of stimulus probability and auditory
      learning.
AB  - Two forms of brainstem plasticity are known to occur: an immediate stimulus
      probability-based and learning-dependent plasticity. Whether these kinds of
      plasticity interact is unknown. We examined this question in a training
      experiment involving three phases: (1) an initial baseline measurement, (2) a 9
      session training paradigm, and (3) a retest measurement. At the outset of the
      experiment, auditory brainstem responses (ABR) were recorded to two unfamiliar
      pitch patterns presented in an oddball paradigm. Then half the participants
      underwent sound-to-meaning training where they learned to match these pitch
      patterns to novel words, with the remaining participants serving as controls who
      received no auditory training. Nine days after the baseline measurement, the
      pitch patterns were re-presented to all participants using the same oddball
      paradigm. Analysis of the baseline recordings revealed an effect of probability:
      when a sound was presented infrequently, the pitch contour was represented less
      accurately in the ABR than when it was presented frequently. After training,
      pitch tracking was more accurate for infrequent sounds, particularly for the
      pitch pattern that was encoded more poorly pre-training. However, the control
      group was stable over the same interval. Our results provide evidence that
      probability-based and learning-dependent plasticity interact in the brainstem. 

PMID- 24291574
TI  - Rewarding effects of the electrical stimulation of the parabrachial complex:
      taste or place preference?
AB  - The lateral parabrachial complex has been related to various emotional-affective
      processes. It has been shown that electrical stimulation of the external Lateral
      Parabrachial (LPBe) nucleus can induce reinforcing effects in place preference
      and taste discrimination tasks but does not appear to support self-stimulation.
      This study examined the relative relevance of place and taste stimuli after
      electrical stimulation of the LPBe nucleus. A learning discrimination task was
      conducted that simultaneously included both sensory indexes (taste and place) in
      order to determine the preference of animals for one or the other. After a taste
      stimulus reversal task, the rewarding effect of stimulation was found to be
      preferentially associated with place. These results are discussed in the context
      of the rewarding action and biological constraints induced by different natural
      and artificial reinforcing agents. 

PMID- 24291575
TI  - A complete assignment of the vibrational spectra of 2-furoic acid based on the
      structures of the more stable monomer and dimer.
AB  - The structural and vibrational properties of cyclic dimer of 2-furoic acid (2FA)
      were predicted by combining the available experimental infrared and Raman spectra
      in the solid phase and ab initio calculations based on density functional theory
      (DFT) with Pople's basis sets. The calculations show that there are two cyclic
      dimers for the title molecule that have been theoretically determined in the gas
      phase, and that only one of them, cis conformer, is present in the solid phase.
      The complete assignment of the 66 normal vibrational modes for the cis cyclic
      dimer was performed using the Pulay's Scaled Quantum Mechanics Force Field
      (SQMFF) methodology. Four strong bands in the infrared spectrum at 1583, 1427,
      1126 and 887 cm(-1) and the group of bands in the Raman spectrum at 1464, 1452,
      1147, 1030, 885, 873, 848, 715 and 590 cm(-1) are characteristic of the dimeric
      form of 2FA in the solid phase. In this work, the calculated structural and
      vibrational properties of both dimeric species were analyzed and compared between
      them. In addition, three types of atomic charges, bond orders, possible charge
      transfer, topological properties of the furan rings, Natural Bond Orbital (NBO)
      and Atoms in Molecules (AIM) theory calculations were employed to study the
      stabilities and intermolecular interactions of the both dimers of 2FA.

PMID- 24291576
TI  - New insights on membrane mediated effects of 1alpha,25-dihydroxy vitamin D3
      signaling in the musculoskeletal system.
AB  - 1alpha,25-Dihydroxy vitamin D3 [1alpha,25(OH)2D3] acts on cells via classical
      steroid hormone receptor-mediated gene transcription and by initiating rapid
      membrane-mediated signaling pathways. Two receptors have been implicated to play
      roles in 1alpha,25(OH)2D3 mediated rapid signaling, the classical nuclear vitamin
      D receptor (VDR) and protein disulfide isomerase, family A, member 3 (Pdia3).
      Long term efforts to investigate the roles of these two receptors demonstrated
      thatPdia3 is located in caveolae, where it interacts with phospholipase A2 (PLA2)
      activating protein (PLAA) and caveolin-1 (Cav-1) to initiate rapid signaling via
      Ca(++)/calmodulin-dependent protein kinase II (CaMKII), PLA2, phospholipase C
      (PLC), protein kinase C (PKC), and ultimately the ERK1/2 family of mitogen
      activated protein kinases (MAPK). VDR is present on the plasma membrane, and it
      is required for 1alpha,25(OH)2D3 induced rapid activation of Src. PDIA3+/- mice
      demonstrate an impaired musculoskeletal phenotype. Moreover, our studies
      examining mineralization of pre-osteoblasts in 3D culture have shown the
      physiological importance of Pdia3 and VDR interaction: knockdown of Pdia3 or VDR
      is characterized by impaired mineralization of the constructs. 

PMID- 24291577
TI  - Realities and myths of the Teresken Syndrome--an evaluation of the exploitation
      of dwarf shrub resources in the Eastern Pamirs of Tajikistan.
AB  - In the Eastern Pamirs extensive livestock herding is the predominant land use
      option and dwarf shrubs - teresken (Krascheninnikovia ceratoides) and to a lesser
      extent wormwood (Artemisia spp.) - are an important source of thermal energy and
      are crucial forage plants, particularly in winter. For the post-Soviet period,
      many papers and reports suggest rapidly increasing exploitation rates with
      sometimes alarming figures for degradation. Conventional knowledge about the
      Pamirs pinpoints the frightening and irreversible extraction of teresken as a
      dwindling resource causing land degradation - termed the 'Teresken Syndrome'.
      However, these publications are based on limited empirical evidence. This paper
      discusses the socio-economic role of dwarf shrubs as fuel and forage - today and
      in the past - and provides an overview of the extent of dwarf shrub distribution
      and degraded areas. Although our observations confirm extensive dwarf shrub
      exploitation, general assumptions of severe desertification as a result of dwarf
      shrub extraction do not yield reliable scenarios. The effects of harvesting on
      the vegetation cover vary widely depending on extraction practices and yields of
      different dwarf shrub-dominated formations. Furthermore, considerable and
      increasing shares of energy needs are satisfied by animal manure and imported
      coal. On the other hand, for low-income households harvesting dwarf shrubs is an
      important and reliable option to ensure both their own household energy supply
      and an income source. We argue that the term 'Teresken Syndrome', which was
      introduced after the emergency replacement of Soviet coal supplies by dwarf
      shrubs in the 1990s, is not appropriate anymore to describe the current use of
      natural resources in the Eastern Pamirs. However, under the current economic
      circumstances the nexus remains that the Pamir people are caught in the dilemma
      of using dwarf shrubs as energy and as forage resource. However, the observed
      negotiation practices concerning competitive use between dwarf shrub extractors
      and herders could be developed into community-based management schemes of this
      common pool resource. 

PMID- 24291578
TI  - Life cycle assessment of pig slurry treatment technologies for nutrient
      redistribution in Denmark.
AB  - Animal slurry management is associated with a range of impacts on fossil resource
      use and the environment. The impacts are greatest when large amounts of nutrient
      rich slurry from livestock production cannot be adequately utilised on adjacent
      land. To facilitate nutrient redistribution, a range of different technologies
      are available. This study comprised a life cycle assessment of the environmental
      impacts from handling 1000 kg of pig slurry ex-animal. Application of untreated
      pig slurry onto adjacent land was compared with using four different treatment
      technologies to enable nutrient redistribution before land application: (a)
      separation by mechanical screw press, (b) screw press separation with composting
      of the solid fraction, (c) separation by decanter centrifuge, and (d) decanter
      centrifuge separation with ammonia stripping of the liquid fraction. Emissions
      were determined based on a combination of values derived from the literature and
      simulations with the Farm-N model for Danish agricultural and climatic
      conditions. The environmental impact categories assessed were climate change,
      freshwater eutrophication, marine eutrophication, terrestrial acidification,
      natural resource use, and soil carbon, nitrogen and phosphorus storage. In all
      separation scenarios, the liquid fraction was applied to land on the pig
      producing (donor) farm and the solid fraction transported to a recipient farm and
      utilised for crop production. Separation, especially by centrifuge, was found to
      result in a lower environmental impact potential than application of untreated
      slurry to adjacent land. Composting and ammonia stripping either slightly
      increased or slightly decreased the environmental impact potential, depending on
      the impact category considered. The relative ranking of scenarios did not change
      after a sensitivity analysis in which coefficients for field emissions of nitrous
      oxide, ammonia and phosphorus were varied within the range cited in the
      literature. Therefore, the best technology to implement in a given situation
      depends on the environmental problem in question, local policy, cost and
      practicality.

PMID- 24291579
TI  - Differential allelopathic effects of Japanese knotweed on willow and cottonwood
      cuttings used in riverbank restoration techniques.
AB  - Using bioengineering techniques to restore areas invaded by Fallopia japonica
      shows promising results. Planting tree cuttings could allow both rapidly re
      establishing a competitive native plant community and reducing F. japonica
      performance. However, F. japonica has been shown to affect native plant species
      through different mechanisms such as allelopathy. This article investigates the
      phytotoxic effect of F. japonica on the resprouting capacity and the growth of
      three Salicaceae species with potential value for restoration. An experimental
      design which physically separates donor pots containing either an individual from
      F. japonica or bare soil from target pots containing cuttings of Populus nigra,
      Salix atrocinerea or Salix viminali was used. Leachates from donor pots were used
      to water target pots. The effects of leachates were evaluated by measuring the
      final biomass of the cuttings. F. japonica leachates inhibited the growth of
      cuttings, and this effect is linked to the emission of polyphenol compounds by F.
      japonica. Leachates also induced changes in soil nitrogen composition. These
      results suggest the existence of allelopathic effects, direct and/or indirect, of
      F. japonica on the growth of Salicaceae species cuttings. However, the three
      species were not equally affected, suggesting that the choice of resistant
      species could be crucial for restoration success. 

PMID- 24291580
TI  - The physical, economic and policy drivers of land conversion to forestry in
      Ireland.
AB  - Land use change is fundamentally a product of the interaction of physical land
      characteristics, economic considerations and agricultural and environmental
      policies. Researchers are increasingly combining physical and socio-economic
      spatial data to investigate the drivers of land-use change in relation to policy
      and economic developments. Focusing on Ireland, this study develops a panel data
      set of annual afforestation over 2811 small-area boundaries between 1993 and 2007
      from vector and raster data sources. Soil type and other physical characteristics
      are combined with the net returns of converting agricultural land to forestry,
      based on the micro-simulation of individual farm incomes, to investigate land
      conversion. A spatial econometric approach is adopted to model the data and a
      range of physical, economic and policy factors are identified as having a
      significant effect on afforestation rates. In addition to the financial returns,
      the availability and quality of land and the implementation of environmental
      protection policies are identified as important factors in land conversion. The
      implications of these factors for the goal of forest expansion are discussed in
      relation to conflicting current and future land use policies. 

PMID- 24291581
TI  - On-farm treatment of swine manure based on solid-liquid separation and biological
      nitrification-denitrification of the liquid fraction.
AB  - In some regions, intensive pig farming has led to soil and water pollution due to
      the over-application of manure as an organic fertilizer, thereby necessitating
      alternative treatment technologies to help manage the large amounts of manure
      generated. The present study seeks to determine the effectiveness of an on-farm
      swine manure treatment plant consisting of a solid-liquid separation phase using
      screw pressing followed by a coagulation-flocculation process, and nitrification
      denitrification of the liquid fraction. Each treatment unit was evaluated for its
      contribution towards reducing the raw manure concentration of solids, organic
      matter, nutrients (nitrogen and phosphorous), metals, and pathogens. The overall
      system presented high removal efficiencies of up to 71% of TS (total solids) and
      97% of TCOD (total chemical oxygen demand). Approximately 97% TKN (total Kjeldahl
      nitrogen) and 89% TP (total phosphorous) removal was achieved. Metals (copper and
      zinc) diminished in the liquid fraction to non-detectable concentrations (<1.0 mg
      L(-1)). As regards microbial removal, total concentration reductions of 3.6 log10
      for Escherichia coli and 1.8 log10 for Salmonella were achieved. Finally, the
      system was evaluated from a financial standpoint. Results indicate that screw
      pressing and coagulation-flocculation for solid-liquid separation and
      nitrification-denitrification of the liquid fraction is a technological
      alternative for reducing the environmental impact of intensive pig farming in a
      given area. 

PMID- 24291582
TI  - Using a new incentive mechanism to improve wastewater sector performance: the
      case study of Italy.
AB  - The system of "Service Objectives", introduced by the Italian National Strategic
      Framework 2007-2013, is an innovative results-oriented programme concerning 4
      thematic areas (education, care for the elderly and children, management of
      municipal solid wastes and integrated water service) in which the Ministry of
      Economic Development and eight Southern Italy districts are involved. The system
      was initially associated to an incentive mechanism which provided subsidies for a
      total amount of EUR 3 billion from the national Underdeveloped Areas Fund,
      according to the achievement of specific targets set for 11 service indicators in
      2013. The indicators used for the integrated water service refer to the
      efficiency in water supply service as well as the coverage of wastewater
      treatment service. The aim of the study is to describe the activities carried out
      in Italy by the ENEA Agency in order to define a new performance indicator for
      wastewater treatment service taking into account the appropriateness and
      efficiency of existing plants equipment and, consequently, evaluating economic
      incentives. The proposed procedure takes into account both wastewater treatment
      demand and quality of wastewater treatment service offered to citizens. Input
      data, provided by the National Institute of Statistics (ISTAT), were elaborated
      in order to define appropriate parameters, with a multi-criteria analysis being
      used to define the new performance indicator. The applicability of the proposed
      procedure was verified considering all the 8 Southern Italy and Island districts
      (Abruzzo, Molise, Campania, Apulia, Basilicata, Calabria, Sicily and Sardinia)
      involved in the programme. The obtained results show that the quality of
      municipal wastewater may influence the calculation of the incentive amount. The
      performance indicators defined in this work might be conveniently extended to
      other contexts similar to the assessed geographical area (Southern Italy and
      Islands). 

PMID- 24291583
TI  - Cysteine-grafted nonwoven geotextile: a new and efficient material for heavy
      metals sorption--part A.
AB  - Cysteine is an interesting biomolecule in the heavy metals trapping field, thanks
      to its amino, thiol and carboxylic groups. This amino acid is indeed present in
      some natural chelating agents: glutathione, phytochelatins and metallothioneins.
      However, cysteine has never been used in remediation processes. When immobilized
      on a polypropylene nonwoven (PP) geotextile, an innovative and eco-friendly
      material is obtained, with potential use in drainage and filtration of
      wastewaters and sediments. PP was first functionalized with acrylic acid using a
      low pressure cold plasma process to bring reactive carboxylic functions onto the
      surface (PP-g-AA). Cysteine was then covalently grafted on this modified PP. The
      cysteine grafting on PP-g-AA was optimized using response surface methodology,
      which allowed concluding that the best conditions of immersion without heating
      consist in: a solution containing 0.229 mol/L of cysteine for 28 h. The materials
      were characterized by Scanning Electron Microscopy, InfraRed Spectroscopy and X
      ray Photoelectron Spectroscopy: evidence of covalent cysteine grafting was given.
      Preliminary sorption tests at 20  degrees C and pH = 4.5 with artificially
      polluted solutions give promising results for divalent heavy metal ions: 95 mg Cu
      (II) (CuSO4 solution), 104 mg Cu (II) and 135 mg Pb(II) (with NO3(-) counter-ion)
      per gram of PP are trapped. 

PMID- 24291584
TI  - Mixed matrix membrane application for olive oil wastewater treatment: process
      optimization based on Taguchi design method.
AB  - Olive oil mill wastewater (OMW) is a concentrated effluent with a high organic
      load. It has high levels of organic chemical oxygen demand (COD) and phenolic
      compounds. This study presents a unique process to treat OMW. The process uses
      ultrafiltration (UF) membranes modified by a functionalized multi wall carbon
      nano-tube (F-MWCNT). The modified tube has an inner diameter of 15-30 nm and is
      added to the OMW treatment process to improve performance of the membrane. Tests
      were done to evaluate the following operating parameters of the UF system;
      pressure, pH and temperature; also evaluated parameters of permeate flux, flux
      decline, COD removal and total phenol rejection. The Taguchi robust design method
      was applied for an optimization evaluation of the experiments. Variance (ANOVA)
      analysis was used to determine the most significant parameters affecting permeate
      flux, flux decline, COD removal and total phenols rejection. Results demonstrated
      coagulation and pH as the most important factors affecting permeate flux of the
      UF. Moreover, pH and F-MWCNT UF had significant positive effects on flux decline,
      COD removal and total phenols rejection. Based on the optimum conditions
      determined by the Taguchi method, evaluations for permeate flux tests; flux
      decline, COD removal and total phenols rejection were about 21.2 (kg/m(2) h),
      12.6%, 72.6% and 89.5%, respectively. These results were in good agreement with
      those predicted by the Taguchi method (i.e.; 22.8 (kg/m(2) h), 11.9%, 75.8 and
      94.7%, respectively). Mechanical performance of the membrane and its application
      for high organic wastewater treatment were determined as strong. 

PMID- 24291585
TI  - The influence of bioaugmentation and biosurfactant addition on bioremediation
      efficiency of diesel-oil contaminated soil: feasibility during field studies.
AB  - The study focused on assessing the influence of bioaugmentation and addition of
      rhamnolipids on diesel oil biodegradation efficiency during field studies.
      Initial laboratory studies (measurement of emitted CO2 and dehydrogenase
      activity) were carried out in order to select the consortium for bioaugmentation
      as well as to evaluate the most appropriate concentration of rhamnolipids. The
      selected consortium consisted of following bacterial taxa: Aeromonas hydrophila,
      Alcaligenes xylosoxidans, Gordonia sp., Pseudomonas fluorescens, Pseudomonas
      putida, Rhodococcus equi, Stenotrophomonas maltophilia, Xanthomonas sp. It was
      established that the application of rhamnolipids at 150 mg/kg of soil was most
      appropriate in terms of dehydrogenase activity. Based on the obtained results,
      four treatment methods were designed and tested during 365 days of field studies:
      I) natural attenuation; II) addition of rhamnolipids; III) bioaugmentation; IV)
      bioaugmentation and addition of rhamnolipids. It was observed that
      bioaugmentation contributed to the highest diesel oil biodegradation efficiency,
      whereas the addition of rhamnolipids did not notably influence the treatment
      process. 

PMID- 24291586
TI  - Trichoderma virens PDR-28: a heavy metal-tolerant and plant growth-promoting
      fungus for remediation and bioenergy crop production on mine tailing soil.
AB  - A heavy metal-tolerant fungus, Trichoderma virens PDR-28, was isolated from
      rhizosphere soil and evaluated for use in remediating mine tailing soil and for
      plant biomass production. PDR-28 exhibited plant growth-promoting traits,
      including 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, acid phosphatase
      and phytase activity, siderophore production, and P solubilization. HMs were more
      available in mine tailing soil inoculated soil with PDR-28 than in uninoculated
      soil; the order of HM bioleaching was Cd > As > Zn > Pb > Cu. PDR-28 effectively
      removed HMs in the order of Pb > Cd > As > Zn > Cu from liquid media containing
      100 mg HM L(-1). Inoculating HM-contaminated mine tailing soil with the fungus
      significantly increased the dry biomass of maize roots (64%) and shoots (56%).
      Chlorophyll, total soluble sugars (reducible and nonreducible), starch, and
      protein contents increased by 46%, 28%, 30%, and 29%, respectively, compared to
      plants grown in uninoculated soil. Inoculation increased heavy metal
      concentrations in maize roots by 25% (Cu) to 62% (Cd) and in shoots by 35% (Cu)
      to 64% (Pb) compared to uninoculated plants. Results suggest that PDR-28 would be
      beneficial for phytostabilization and plant biomass production as a potential
      source of biofuel in the quest for renewable energy. 

PMID- 24291587
TI  - Proapoptotic effects of the novel proteasome inhibitor b-AP15 on multiple myeloma
      cells and natural killer cells.
AB  - The small molecule b-AP15 is a novel inhibitor of proteasome deubiquitination.
      Recent studies have shown that b-AP15 displays antitumor activity in several
      preclinical, solid tumor models. In this study, we show that b-AP15 triggers time
      and dose-dependent apoptosis of the human multiple myeloma (MM) cell lines
      RPMI8226 and U266, as determined by phosphatidylserine exposure. Apoptosis was
      dependent on caspase activation and was partially dependent on cathepsin D.
      Furthermore, b-AP15 triggered processing of pro-caspase-3 and cleavage of poly
      (ADP-ribose) polymerase in MM cells. b-AP15 also induced caspase-independent
      apoptosis in primary human natural killer cells. We also demonstrate that b-AP15
      induces activation of the mitochondrial apoptosis pathway in MM cells, with
      activation of the proapoptotic protein Bax and a pronounced loss of the
      mitochondrial transmembrane potential. The latter events, however, appeared
      largely independent of caspase activation. Our data suggest that proteasome
      deubiquitinase inhibitors may have potential for treatment of multiple myeloma
      patients. 

PMID- 24291588
TI  - Who should learn cardiac rhythm interpretation and how?

PMID- 24291589
TI  - Historical vignette: the first cardiac first responders.

PMID- 24291591
TI  - A support vector machine for predicting defibrillation outcomes from waveform
      metrics.
AB  - BACKGROUND: Algorithms to predict shock success based on VF waveform metrics
      could significantly enhance resuscitation by optimising the timing of
      defibrillation. OBJECTIVE: To investigate robust methods of predicting
      defibrillation success in VF cardiac arrest patients, by using a support vector
      machine (SVM) optimisation approach. METHODS: Frequency-domain (AMSA, dominant
      frequency and median frequency) and time-domain (slope and RMS amplitude) VF
      waveform metrics were calculated in a 4.1Y window prior to defibrillation.
      Conventional prediction test validity of each waveform parameter was conducted
      and used AUC>0.6 as the criterion for inclusion as a corroborative attribute
      processed by the SVM classification model. The latter used a Gaussian radial
      basis-function (RBF) kernel and the error penalty factor C was fixed to 1. A two
      fold cross-validation resampling technique was employed. RESULTS: A total of 41
      patients had 115 defibrillation instances. AMSA, slope and RMS waveform metrics
      performed test validation with AUC>0.6 for predicting termination of VF and
      return-to-organised rhythm. Predictive accuracy of the optimised SVM design for
      termination of VF was 81.9% (+/- 1.24 SD); positive and negative predictivity
      were respectively 84.3% (+/- 1.98 SD) and 77.4% (+/- 1.24 SD); sensitivity and
      specificity were 87.6% (+/- 2.69 SD) and 71.6% (+/- 9.38 SD) respectively.
      CONCLUSIONS: AMSA, slope and RMS were the best VF waveform frequency-time
      parameters predictors of termination of VF according to test validity assessment.
      This a priori can be used for a simplified SVM optimised design that combines the
      predictive attributes of these VF waveform metrics for improved prediction
      accuracy and generalisation performance without requiring the definition of any
      threshold value on waveform metrics.

PMID- 24291590
TI  - Shockable rhythms and defibrillation during in-hospital pediatric cardiac arrest.
AB  - OBJECTIVE: To analyze the results of cardiopulmonary resuscitation (CPR) that
      included defibrillation during in-hospital cardiac arrest (IH-CA) in children.
      METHODS: A prospective multicenter, international, observational study on
      pediatric IH-CA in 12 European and Latin American countries, during 24 months.
      Data from 502 children between 1 month and 18 years were collected using the
      Utstein template. Patients with a shockable rhythm that was treated by electric
      shock(s) were included. The primary endpoint was survival at hospital discharge.
      Univariate logistic regression analysis was performed to find outcome factors.
      RESULTS: Forty events in 37 children (mean age 48 months, IQR: 7-15 months) were
      analyzed. An underlying disease was present in 81.1% of cases and 24.3% had a
      previous CA. The main cause of arrest was a cardiac disease (56.8%). In 17
      episodes (42.5%) ventricular fibrillation (VF) or pulseless ventricular
      tachycardia (pVT) was the first documented rhythm, and in 23 (57.5%) it developed
      during CPR efforts. In 11 patients (27.5%) three or more shocks were needed to
      achieve defibrillation. Return of spontaneous circulation (ROSC) was obtained in
      25 cases (62.5%), that was sustained in 20 (50.0%); however only 12 children
      (32.4%) survived to hospital discharge. Children with VF/pVT as first documented
      rhythm had better sustained ROSC (64.7% vs. 39.1%, p=0.046) and survival to
      hospital discharge rates (58.8% vs. 21.7%, p=0.02) than those with subsequent
      VF/pVT. Survival rate was inversely related to duration of CPR. Clinical outcome
      was not related to the cause or location of arrest, type of defibrillator and
      waveform, energy dose per shock, number of shocks, or cumulative energy dose,
      although there was a trend to better survival with higher doses per shock (25.0%
      with <2Jkg(-1), 43.4% with 2-4Jkg(-1) and 50.0% with >4Jkg(-1)) and worse with
      higher number of shocks and cumulative energy dose. CONCLUSION: The termination
      of pediatric VF/pVT in the IH-CA setting is achieved in a low percentage of
      instances with one electrical shock at 4Jkg(-1). When VF/pVT is the first
      documented rhythm, the results of defibrillation are better than in the case of
      subsequent VF/pVT. No clear relationship between defibrillation protocol and ROSC
      or survival has been observed. The optimal pediatric defibrillation dose remains
      to be determined; therefore current resuscitation guidelines cannot be considered
      evidence-based, and additional research is needed.

PMID- 24291592
TI  - Press hard - but perhaps not too hard.

PMID- 24291593
TI  - Tortuosity and other vessel attributes for arterioles and venules of the human
      cerebral cortex.
AB  - Despite its demonstrated potential in the diagnosis and/or staging of disease,
      especially in oncology, tortuosity has not received a formal and unambiguous
      clinical definition yet. Using idealized three-dimensional vessel models (wavy
      helices) with known characteristics, we first demonstrate that, among various
      possible tortuosity indices, the standard deviation of the curvature Ksd best
      satisfies i) scale invariance and ii) positive monotonic response with respect to
      the amplitude and frequency of vessel oscillations. Ksd can thus be considered as
      a robust measure of tortuosity. On the contrary, indices previously considered as
      tortuosity metrics, such as the distance factor metrics (DFM), are highly scale
      dependent and inappropriate for that purpose. The tortuosity and other vessel
      attributes (curvature, length-to-diameter ratio (LDR),...) of more than 15,000
      cortical vessels are subsequently studied, establishing their statistical
      properties as a function of the vessel nature (arterioles versus venules) or
      topological order (hierarchical position). In particular, arterioles have a
      higher LDR than venules, but the two kinds of vessels have the same mean
      curvature and tortuosity. Moreover, the lower the order of the vessels, i.e. the
      nearer to the capillary network, the more curved and tortuous they are. These
      results provide an essential reference both for diagnosis and for a future large
      reconstruction of the cerebral microvascular network. 

PMID- 24291594
TI  - Comparative effectiveness of platelet-rich plasma injections for treating knee
      joint cartilage degenerative pathology: a systematic review and meta-analysis.
AB  - OBJECTIVE: To explore the effectiveness of platelet-rich plasma (PRP) in treating
      cartilage degenerative pathology in knee joints. DATA SOURCES: Electronic
      databases, including PubMed and Scopus, were searched from the earliest record to
      September 2013. STUDY SELECTION: We included single-arm prospective studies,
      quasi-experimental studies, and randomized controlled trials that used PRP to
      treat knee chondral degenerative lesions. Eight single-arm studies, 3 quasi
      experimental studies, and 5 randomized controlled trials were identified,
      comprising 1543 participants. DATA EXTRACTION: We determined effect sizes for the
      selected studies by extracting changes in functional scales after the
      interventions and compared the PRP group pooled values with the pretreatment
      baseline and the groups receiving placebo or hyaluronic acid (HA) injections.
      DATA SYNTHESIS: PRP injections in patients with knee degenerative pathology
      showed continual efficacy for 12 months compared with their pretreatment
      condition. The effectiveness of PRP was likely better and more prolonged than
      that of HA. Injection doses <=2, the use of a single-spinning approach, and lack
      of additional activators led to an uncertainty in the treatment effects. Patients
      with lower degrees of cartilage degeneration achieved superior outcomes as
      opposed to those affected by advanced osteoarthritis. CONCLUSIONS: PRP
      application improves function from basal evaluations in patients with knee joint
      cartilage degenerative pathology and tends to be more effective than HA
      administration. Discrepancy in the degenerative severity modifies the treatment
      responses, leading to participants with lower degrees of degeneration benefiting
      more from PRP injections.

PMID- 24291595
TI  - Relationship between shoulder pain and kinetic and temporal-spatial variability
      in wheelchair users.
AB  - OBJECTIVE: To examine intra-individual variability of kinetic and temporal
      spatial parameters of wheelchair propulsion as a function of shoulder pain in
      manual wheelchair users (MWUs). DESIGN: Cohort. SETTING: University research
      laboratory. PARTICIPANTS: Adults with physical disabilities (N=26) who use a
      manual wheelchair for mobility full time (>80% ambulation). INTERVENTIONS:
      Participants propelled their own wheelchairs with force-sensing wheels at a
      steady-state pace on a dynamometer at 3 speeds (self-selected, 0.7m/s, 1.1m/s)
      for 3 minutes. Temporal-spatial and kinetic data were recorded unilaterally at
      the hand rim. MAIN OUTCOME MEASURES: Shoulder pain was quantified with the
      Wheelchair Users Shoulder Pain Index. Intra-individual mean, SD, and coefficient
      of variation (CV=mean/SD) with kinetic and temporal-spatial metrics were
      determined at the handrim. RESULTS: There were no differences in mean kinetic and
      temporal-spatial metrics as a function of pain group (P values >.016). However,
      individuals with pain displayed less relative variability (CV) in peak resultant
      force and push time than pain-free individuals (P<.016). CONCLUSIONS: Shoulder
      pain had no influence on mean kinetic and temporal-spatial propulsion variables
      at the handrim; however, group differences were found in relative variability.
      These results suggest that intra-individual variability analysis is sensitive to
      pain. We propose that variability analysis may offer an approach for earlier
      identification of MWUs at risk for developing shoulder pain.

PMID- 24291596
TI  - Timed up and go, cognitive, and quality-of-life correlates in Parkinson's
      disease.
AB  - OBJECTIVE: To examine the relationship between Timed Up and Go (TUG) performance,
      verbal executive function (EF) performance, and quality-of-life (QOL) measures in
      Parkinson's disease (PD). DESIGN: Cross-sectional. SETTING: Sixteen movement
      disorder centers from across the United States. PARTICIPANTS: Patients with PD
      (N=1964). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: TUG test,
      immediate and delayed 5-word recall, verbal fluency, PD QOL Questionnaire.
      RESULTS: TUG performance and verbal EF performance were significantly associated
      with, and predictors of, QOL measures, having the greatest association and
      predictability with the mobility domain of the QOL measures. CONCLUSIONS: The TUG
      test and verbal EF tests have QOL correlates, making the combined evaluation of
      mobility, cognitive, and QOL decline a potential examination tool to evaluate the
      sequelae of PD.

PMID- 24291597
TI  - Physical exercise interventions for improving performance-based measures of
      physical function in community-dwelling, frail older adults: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review to determine the efficacy of exercise
      based interventions on improving performance-based measures of physical function
      and markers of physical frailty in community-dwelling, frail older people. DATA
      SOURCES: Comprehensive bibliographic searches in MEDLINE, the Cochrane Library,
      PEDro, and CINAHL databases were conducted (April 2013). STUDY SELECTION:
      Randomized controlled trials of community-dwelling older adults, defined as frail
      according to physical function and physical difficulties in activities of daily
      living (ADL). Included trials had to compare an exercise intervention with a
      control or another exercise intervention, and assess performance-based measures
      of physical function such as mobility and gait, or disability in ADL. DATA
      EXTRACTION: Two review authors independently screened the search results and
      performed data extraction and risk of bias assessment. Nineteen trials were
      included, 12 of them comparing exercise with an inactive control. Most exercise
      programs were multicomponent. DATA SYNTHESIS: Meta-analysis was performed for the
      comparison of exercise versus control with the inverse variance method under the
      random-effects models. When compared with control interventions, exercise was
      shown to improve normal gait speed (mean difference [MD]=.07m/s; 95% confidence
      interval [CI], .04-.09), fast gait speed (MD=.08m/s; 95% CI, .02-.14), and the
      Short Physical Performance Battery (MD=2.18; 95% CI, 1.56-2.80). Results are
      inconclusive for endurance outcomes, and no consistent effect was observed on
      balance and the ADL functional mobility. The evidence comparing different
      modalities of exercise is scarce and heterogeneous. CONCLUSIONS: Exercise has
      some benefits in frail older people, although uncertainty still exists with
      regard to which exercise characteristics (type, frequency, duration) are most
      effective.

PMID- 24291599
TI  - The reply.

PMID- 24291598
TI  - TALE: a tale of genome editing.
AB  - Transcription activator-like effectors (TALEs), first identified in Xanthomonas
      bacteria, are naturally occurring or artificially designed proteins that modulate
      gene transcription. These proteins recognize and bind DNA sequences based on a
      variable numbers of tandem repeats. Each repeat is comprised of a set of ~ 34
      conserved amino acids; within this conserved domain, there are usually two amino
      acids that distinguish one TALE from another. Interestingly, TALEs have revealed
      a simple cipher for the one-to-one recognition of proteins for DNA bases.
      Synthetic TALEs have been used to successfully target genes in a variety of
      species, including humans. Depending on the type of functional domain that is
      fused to the TALE of interest, these proteins can have diverse biological
      effects. For example, after binding DNA, TALEs fused to transcriptional
      activation domains can function as robust transcription factors (TALE-TFs), while
      fused to restriction endonucleases (TALENs) can cut DNA. Targeted genome editing,
      in theory, is capable of modifying any endogenous gene sequence of interest; this
      can be performed in cells or organisms, and may be applied to clinical gene-based
      therapies in the future. With current technologies, highly accurate, specific,
      and reliable gene editing cannot be achieved. Thus, recognition and binding
      mechanisms governing TALE biology are currently hot research areas. In this
      review, we summarize the major advances in TALE technology over the past several
      years with a focus on the interaction between TALEs and DNA, TALE design and
      construction, potential applications for this technology, and unique
      characteristics that make TALEs superior to zinc finger endonucleases.

PMID- 24291600
TI  - The reply.

PMID- 24291601
TI  - Comparative proteomics reveals association of early accumulated proteins in
      conferring butachlor tolerance in three N(2)-fixing Anabaena spp.
AB  - Butachlor an extensively used rice field herbicide negatively affects the
      cyanobacterial proliferation, yet the molecular mechanism underlying its toxicity
      in diazotrophic cyanobacteria is largely unknown. The present study focuses on
      the comparative proteomics to decode the molecular basis of butachlor
      toxicity/tolerance in three Anabaena species e.g. Anabaena sp. PCC 7120, Anabaena
      doliolum and Anabaena L31. 75 differentially expressed proteins from each
      Anabaena sp. included those involved in photosynthesis, C, N and protein
      metabolism, redox homeostasis, and signal transduction. While early accumulated
      proteins related to photosynthesis (atpA, atpB), carbon metabolism (glpx, fba and
      prk), protein folding (groEL, PPIase), regulation (orrA) and other function (OR,
      akr) appeared crucial for tolerance of Anabaena L31, the late accumulated
      proteins in Anabaena 7120 presumably offer acclimation during prolonged exposure
      to butachlor. Contrary to the above, a multitude of down-accumulated proteins vis
      a-vis metabolisms augment sensitivity of A. doliolum to butachlor. A cluster of
      high abundant proteins (atpA, groEL, OR, AGTase, Alr0803, Alr0806, Alr3090,
      Alr3199, All4050 and All4051) common across the three species may be taken as
      markers for butachlor tolerance and deserve exploitation for stress management
      and transgenic development. BIOLOGICAL SIGNIFICANCE: Cyanobacteria offer an eco
      friendly alternative to chemical fertilizers for increasing productivity,
      especially in rice cultivation. This study is the first to compare the proteome
      of three diazotrophic cyanobacteria subjected to butachlor, a pre-emergent
      herbicide extensively used in rice paddy. Changes in protein dynamics over time
      along with physiological and biochemical attributes clearly provide a
      comprehensive overview on differential tolerance of Anabaena species to
      butachlor. Molecular docking further added a new dimension in identification of
      potential protein candidates for butachlor stress management in cyanobacteria.
      This study strongly recommends combined application of Anabaena spp. A. L31 and
      A. PCC7120 as biofertilizer in paddy fields undergoing butachlor treatment.

PMID- 24291603
TI  - Reticulocytes from cryopreserved erythroblasts support Plasmodium vivax infection
      in vitro.
AB  - Plasmodium vivax is the most widely distributed human malaria parasite. Despite
      its importance, both clinical research and basic research have been hampered by
      lack of a convenient in vitro culture system, in part due to the parasite's
      infection preference of reticulocytes rather than mature erythrocytes. The use of
      reticulocyte-producing hematopoietic stem cell culture has been proposed for the
      maintenance of the parasite, but good numbers of reticulocytes and P. vivax
      parasites sufficient for practical use in research have been difficult to produce
      from this system. Here, we report an improved method of hematopoietic stem cell
      culture for P. vivax infection, which requires less time and produces higher or
      equivalent percentage of reticulocytes than previously reported systems.
      Reticulocytes were cultured from cryopreserved erythroblasts that were frozen
      after 8day-cultivation of purified CD34+ cells from human umbilical cord blood.
      This method of production allowed the recovery of reticulocytes in a shorter time
      than with continuous stem cell culture. We obtained a relatively high percentage
      of peak reticulocyte production by using co-cultivation with a mouse stromal cell
      line. Using P. vivax mature stage parasites obtained from infected Aotus monkeys,
      we observed substantial numbers (up to 0.8% of the total number of the cells) of
      newly invaded reticulocytes 24h after initial cultivation. The addition of fresh
      reticulocytes after 48h culture, however, did not result in significant increase
      of second cycle reticulocyte invasion. Assays of invasion inhibition with
      specific antibodies were successful with this system, demonstrating potential for
      study of biological processes as well as the conditions necessary for long-term
      maintenance of P. vivax in vitro. 

PMID- 24291604
TI  - Biogeography of tropical Indo-West Pacific parasites: a cryptic species of
      Transversotrema and evidence for rarity of Transversotrematidae (Trematoda) in
      French Polynesia.
AB  - We sought transversotrematid trematodes from French Polynesian fishes by
      examining 304 individual scaled fishes of 53 species from seven families known to
      harbour the family elsewhere. A single species was found at two locations in the
      Tuamotus Archipelago on two species of Chaetodontidae (Chaetodon auriga and
      Chaetodon ephippium) and one species of Lutjanidae (Lutjanus gibbus). The species
      closely resembles Transversotrema borboleta Hunter & Cribb, 2012 from
      chaetodontids and lutjanids of the northern Great Barrier Reef (GBR) but differs
      from it consistently in 8 base positions of ITS2 rDNA. This level of variation
      exceeds that between some clearly morphologically distinct pairs of species of
      Transversotrema and the form from French Polynesia is thus interpreted as a
      distinct, though cryptic, species and named Transversotrema polynesiae n. sp. The
      new species forms part of a complex of species, here characterised as the T.
      borboleta complex, associated with chaetodontids and lutjanids in the tropical
      Indo-West Pacific. Most of the putative species within this complex are yet to be
      described. Comparison of identical numbers of matched samples of fishes from
      French Polynesia, Heron Island (southern GBR) and Lizard Island (northern GBR)
      revealed 1, 4 and 10 species of Transversotrema respectively suggesting that the
      French Polynesian fauna is depauperate for this family. In addition to those
      species apparently missing from suitable hosts in French Polynesia, several
      species from further west infect fishes (especially Nemipteridae) that are
      themselves absent from French Polynesia. This dramatic east-west decline in
      richness contrasts strongly with what is known for monogeneans, which appear to
      maintain their richness over the same scale, and is more precipitate than is
      known for other groups of trematodes. The decline might be explained in part by
      the absence of the as yet unknown first intermediate hosts in French Polynesia.
      However, we predict that it is explained by other life cycle traits. We
      hypothesise that the characters of large short-lived cercariae, short-lived
      miracidia, the absence in the life-cycle of second intermediate hosts that are
      capable of transporting the species, and definitive and first intermediate hosts
      that have limited vagility combine to give marine Transversotrematidae limited
      dispersal capacity and a propensity for localised speciation. 

PMID- 24291602
TI  - LTQ-XL mass spectrometry proteome analysis expands the Pseudomonas aeruginosa
      AmpR regulon to include cyclic di-GMP phosphodiesterases and phosphoproteins, and
      identifies novel open reading frames.
AB  - Pseudomonas aeruginosa is well known for its antibiotic resistance and intricate
      regulatory network, contributing to its success as an opportunistic pathogen.
      This study is an extension of our transcriptomic analyses (microarray and RNA
      Seq) to understand the global changes in PAO1 upon deleting a gene encoding a
      transcriptional regulator AmpR, in the presence and absence of beta-lactam
      antibiotic. This study was performed under identical conditions to explore the
      proteome profile of the ampR deletion mutant (PAODeltaampR) using LTQ-XL mass
      spectrometry. The proteomic data identified ~53% of total PAO1 proteins and
      expanded the master regulatory role of AmpR in determining antibiotic resistance
      and multiple virulence phenotypes in P. aeruginosa. AmpR proteome analysis
      identified 853 AmpR-dependent proteins, which include 102 transcriptional
      regulators and 21 two-component system proteins. AmpR also regulates cyclic di
      GMP phosphodiesterases (PA4367, PA4969, PA4781) possibly affecting major
      virulence systems. Phosphoproteome analysis also suggests a significant role for
      AmpR in Ser, Thr and Tyr phosphorylation. These novel mechanisms of gene
      regulation were previously not associated with AmpR. The proteome analysis also
      identified many unannotated and misannotated ORFs in the P. aeruginosa genome.
      Thus, our data sheds light on important virulence regulatory pathways that can
      potentially be exploited to deal with P. aeruginosa infections. BIOLOGICAL
      SIGNIFICANCE: The AmpR proteome data not only confirmed the role of AmpR in
      virulence and resistance to multiple antibiotics, but also expanded the perimeter
      of AmpR regulon. The data presented here points to the role of AmpR in regulating
      cyclic di-GMP levels and phosphorylation of Ser, Thr and Tyr, adding another
      dimension to the regulatory functions of AmpR. We also identify some previously
      unannotated/misannotated ORFs in the P. aeruginosa genome, indicating the
      limitations of existing ORF analyses software. This study will contribute towards
      understanding complex genetic organization of P. aeruginosa. Whole genome
      proteomic picture of regulators at higher nodal positions in the regulatory
      network will not only help us link various virulence phenotypes but also design
      novel therapeutic strategies.

PMID- 24291605
TI  - Larval stages of the bluefin tuna blood fluke Cardicola opisthorchis (Trematoda:
      Aporocotylidae) found from Terebella sp. (Polychaeta: Terebellidae).
AB  - We found aporocotylid larval stages (sporocysts and cercariae) from five
      individuals of terebellid polychaete Terebella sp., which were collected from
      seabed substrate and ropes and floats attached to tuna cages in a tuna farm on
      the coast of Tsushima Island, Nagasaki, Japan. Nucleotide sequences of the
      regions of internal transcribed spacer 2 ribosomal DNA and 28S ribosomal DNA from
      these larval stages were 100% identical to those of Cardicola opisthorchis
      registered in GenBank. C. opisthorchis is a pathogen causing blood fluke
      infection of Pacific bluefin tuna Thunnus orientalis, which is considered to have
      a significant impact on the Japanese Pacific bluefin tuna aquaculture industry.
      This is the first description of the intermediate host of C. opisthorchis. This
      indicates that the life cycle of C. opisthorchis is completed within tuna farms
      in this area. 

PMID- 24291606
TI  - Determination of YZG-331 in mouse plasma using liquid chromatography-tandem mass
      spectrometry.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the determination of YZG-331 in mouse plasma was developed. Plasma
      samples containing YZG-331 and YZG-441 (internal standard, IS) were prepared
      using a simple protein precipitation by the addition of acetonitrile. Thermo
      Scientific TSQ Quantum triple quadrupole system with multiple reaction monitoring
      (MRM) positive scanning mode was applied. The separation was performed on a
      ZorbaxSB-C18 column (3.5MUm, 2.1mm*100mm) at a flow rate of 0.2mL/min, using
      acetonitrile/water containing 0.1% formic acid (v/v) as mobile phase. The MS/MS
      ion transit ions monitored were 386->254 for YZG-331 and 400->268 for IS. Linear
      detection responses were obtained for YZG-331 ranging from 25 to 5000ng/mL and
      the lower limits of quantitation (LLOQ) for the compound was 25ng/mL. The intra-
      and inter-day precisions (R.S.D.%) were within 12.6% for all analytes, while the
      deviation of assay accuracies was within +/-6.9%. The average recoveries of
      analytes were greater than 94.3%. The analytes were proved to be stable during
      all sample storage, preparation and analytic procedures. The method was
      successfully applied to the pharmacokinetic studies of YZG-331 in mice. 

PMID- 24291607
TI  - Determination of three triterpene alcohols in rat plasma after oral
      administration of pollen of Brassica campestris based on the utilization of fetal
      bovine serum as surrogate matrix.
AB  - 24-Dehydropollinstanol (DEH), 24-methylene cholesterol (MET) and 31
      norcycloartenol (NOR) are the functional triterpene alcohols of pollen of
      Brassica campestris. To study the pharmacokinetics of the above components of
      pollen of B. campestris in rats, a liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method was developed. To avoid the interference of endogenous MET in
      rat plasma, fetal bovine serum (FBS) was selected as surrogate matrix and
      validated. Rat plasma was liquid-liquid extracted, then the chromatographic
      separation was conducted on a poroshell 120 SB C18 column (2.7MUm, 2.1mm*50mm) at
      38 degrees C within 5.6min utilizing a gradient elution with a mobile phase
      consisting of (A) 0.1% formic acid in water and (B) 0.1% formic acid in methanol.
      The detection was performed on a triple quadrupole tandem mass spectrometer in
      multiple reaction monitoring (MRM) mode using positive atmospheric pressure
      chemical ionization (APCI). The method was validated over the concentration of
      9.8-1560ng/ml; the inter-and-intra-day precisions (RSD %) were <=7.8%, and the
      accuracies (RE %) were -5.3% to 12.2%, the extraction recovery ranged from 73.5%
      to 106.9% for all of these analytes, and no obvious matrix effect was observed.
      The developed method was applied successfully to study the pharmacokinetics of
      DEH, MET and NOR in rats after oral administration of pollen of B. campestris. 

PMID- 24291608
TI  - Development and validation of a dried blood spot assay for the quantification of
      ribavirin using liquid chromatography coupled to mass spectrometry.
AB  - Efficient, inexpensive and sensitive assays for the measurement of drugs are of
      interest for pharmacokinetic and pharmacodynamics (PK-PD) analysis. Dried blood
      spots (DBS) are a unique bioanaltyical matrix with the potential to fulfill this
      interest for the measurement of numerous analytes. Here we describe the
      development and validation of a reversed-phase high performance liquid
      chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the
      determination of ribavirin (RBV) in DBS. A 3mm punch from spotted and dried whole
      blood was extracted in methanol utilizing isotopically labeled internal standard
      for LC-MS/MS analysis. Validation was performed over a range of 0.05MUg/mL to
      10.0MUg/mL and the method was shown to be precise (coefficient of variation
      <=15%) and accurate (within +/-15% of control). These acceptance criteria were
      met for hematocrit ranges of 20-54%, for center versus edge punches and for spot
      volumes from 10 to 60MUL. RBV was stable for up to 140 days at room temperature
      and -20 degrees C as well as for three freeze/thaw cycles. Correlation of RBV in
      DBS versus in plasma yielded r(2)>=0.98 demonstrating that DBS can be used as an
      alternative to plasma for PK-PD studies in human subjects. 

PMID- 24291609
TI  - Anti-proliferative activity of 25-hydroxyvitamin D3 in human prostate cells.
AB  - 1alpha-Hydroxylation of 25-hydroxyvitamin D3 is believed to be essential for its
      biological effects. In this study, we evaluated the biological activity of
      25(OH)D3 itself comparing with the effect of cell-derived 1alpha,25
      dihydroxyvitamin D3 (1alpha,25(OH)2D3). First, we measured the cell-derived
      1alpha,25(OH)2D3 level in immortalized human prostate cell (PZ-HPV-7) using
      [(3)H]-25(OH)D3. The effects of the cell-derived 1alpha,25(OH)2D3 on vitamin D3
      24-hydroxylase (CYP24A1) mRNA level and the cell growth inhibition were
      significantly lower than the effects of 25(OH)D3 itself added to cell culture. 25
      Hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) gene knockdown had no significant
      effects on the 25(OH)D3-dependent effects, whereas vitamin D receptor (VDR) gene
      knockdown resulted in a significant decrease in the 25(OH)D3-dependent effects.
      These results strongly suggest that 25(OH)D3 can directly bind to VDR and exerts
      its biological functions. DNA microarray and real-time RT-PCR analyses suggest
      that semaphorin 3B, cystatin E/M, and cystatin D may be involved in the
      antiproliferative effect of 25(OH)D3. 

PMID- 24291610
TI  - Laparoscopic sleeve gastrectomy ameliorates mRNA expression of inflammation
      related genes in subcutaneous adipose tissue but not in peripheral monocytes of
      obese patients.
AB  - Low-grade inflammation links obesity, insulin resistance, and cardiovascular
      diseases. We investigated the effects of laparoscopic sleeve gastrectomy (LSG) on
      expression profile of genes involved in inflammatory pathways in subcutaneous
      adipose tissue (SCAT) and peripheral monocytes (PM). At baseline, obese group had
      significantly increased mRNA expression of proinflammatory chemokines (CCL-3, 
      17, -22), chemokine receptor CCR1 and cytokines (IL-10, IL-18) in SCAT and
      chemokine and other proinflammatory receptors (CCR-1, -2, -3, TLR-2, -4) in PM
      relative to control group. LSG decreased body weight, improved metabolic profile
      and reduced mRNA expression of up-regulated chemokine receptors, chemokines and
      cytokines in SCAT. In contrast, expression profiles in PM were largely unaffected
      by LSG. We conclude that LSG improved proinflammatory profile in subcutaneous fat
      but not in peripheral monocytes. The sustained proinflammatory and chemotactic
      profile in PM even 2 years after LSG may contribute to partial persistence of
      metabolic complications in obese patients after metabolic surgery.

PMID- 24291611
TI  - Temporal trend and age-dependent serum concentration of phenolic organohalogen
      contaminants in Japanese men during 1989-2010.
AB  - The temporal trend in serum concentrations of phenolic organohalogen contaminants
      (POCs) were investigated in two age groups of men from Kyoto, Japan, from 1989 to
      2010. These concentrations and trends were compared with neutral contaminants
      including polychlorinated biphenyls (PCBs) and pesticides. Serum concentrations
      of pentachlorophenol (PenCP) and 4-hydroxy-PCB187 were age-dependent and
      decreased to approximately one-half during the two decades, whereas no
      contamination trends were observed for 2,4,6-tribromophenol (TriBP),
      tetrabromobisphenol A (TBBPA) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6
      OH-BDE47). 6-OH-BDE47 was found in all samples (up to 3000 pg/g wet weight),
      whereas TBBPA was detected in 17 of 60 serum samples (up to 950 pg/g wet weight).
      The concentrations of TriBP, TBBPA and 6-OH-BDE47 were not correlated to those of
      PenCP or 4-OH-PCB187 in either age group, suggesting the different kinetics on
      exposure routes and fate between these brominated and chlorinated POCs.

PMID- 24291612
TI  - Evaluation of effects of long term exposure on lethal toxicity with mammals.
AB  - The relationship between exposure time (LT50) and lethal exposure concentration
      (LC50) has been evaluated over relatively long exposure times using a novel
      parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model
      equation, ln(LT50) = aLC50(nu) + b, where a, b and nu are constants, was
      evaluated by plotting lnLT50 against LC50 using available toxicity data based on
      inhalation exposure from 7 species of mammals. With each specific toxicant a
      single consistent relationship was observed for all mammals with nu always <1.
      Use of NLT as a long term toxicity point provided a valuable limiting point for
      long exposure times. With organic compounds, the Kow can be used to calculate the
      model constants a and v where these are unknown. The model can be used to
      characterise toxicity to specific mammals and then be extended to estimate
      toxicity at any exposure time with other mammals. 

PMID- 24291613
TI  - Effects of oil dispersant and oil on sorption and desorption of phenanthrene with
      Gulf Coast marine sediments.
AB  - Effects of a model oil dispersant (Corexit EC9500A) on sorption/desorption of
      phenanthrene were investigated with two marine sediments. Kinetic data revealed
      that the presence of the dispersant at 18 mg/L enhanced phenanthrene uptake by up
      to 7%, whereas the same dispersant during desorption reduced phenanthrene
      desorption by up to 5%. Sorption isotherms confirmed that at dispersant
      concentrations of 18 and 180 mg/L, phenanthrene uptake progressively increased
      for both sediments. Furthermore, the presence of the dispersant during desorption
      induced remarkable sorption hysteresis. The effects were attributed to added
      phenanthrene affinity and capacity due to sorption of the dispersant on the
      sediments. Dual-mode models adequately simulated sorption isotherms and kinetic
      data in the presence of the dispersant. Water accommodated oil (WAO) and
      dispersant-enhanced WAO increased phenanthrene sorption by up to 22%. This
      information is important for understanding roles of oil dispersants on the
      distribution and transport of petroleum PAHs in seawater-sediments. 

PMID- 24291616
TI  - Anti-IgE therapy for allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a severe type of asthma. Some
      cases are resistant to treatment, even with regular use of antiasthmatic drugs
      and antifungal agents. The diagnosis of ABPA was made in a 40-year-old patient
      with ABPA according to the Rosenberg-Patterson criteria. Symptoms were not
      controlled despite regular use of antiasthmatic drugs, daily systemic steroids,
      and antifungal agents. Omalizumab, administered in an attempt to stabilize these
      uncontrolled symptoms, was effective with no adverse events. Our experience
      suggests omalizumab is a potential candidate drug for controlling steroid
      dependent ABPA. 

PMID- 24291614
TI  - Striatal dysfunction during reversal learning in unmedicated schizophrenia
      patients.
AB  - Subjects with schizophrenia are impaired at reinforcement-driven reversal
      learning from as early as their first episode. The neurobiological basis of this
      deficit is unknown. We obtained behavioral and fMRI data in 24 unmedicated,
      primarily first episode, schizophrenia patients and 24 age-, IQ- and gender
      matched healthy controls during a reversal learning task. We supplemented our
      fMRI analysis, focusing on learning from prediction errors, with detailed
      computational modeling to probe task solving strategy including an ability to
      deploy an internal goal directed model of the task. Patients displayed reduced
      functional activation in the ventral striatum (VS) elicited by prediction errors.
      However, modeling task performance revealed that a subgroup did not adjust their
      behavior according to an accurate internal model of the task structure, and these
      were also the more severely psychotic patients. In patients who could adapt their
      behavior, as well as in controls, task solving was best described by cognitive
      strategies according to a Hidden Markov Model. When we compared patients and
      controls who acted according to this strategy, patients still displayed a
      significant reduction in VS activation elicited by informative errors that
      precede salient changes of behavior (reversals). Thus, our study shows that VS
      dysfunction in schizophrenia patients during reward-related reversal learning
      remains a core deficit even when controlling for task solving strategies. This
      result highlights VS dysfunction is tightly linked to a reward-related reversal
      learning deficit in early, unmedicated schizophrenia patients. 

PMID- 24291615
TI  - Integration of sparse multi-modality representation and anatomical constraint for
      isointense infant brain MR image segmentation.
AB  - Segmentation of infant brain MR images is challenging due to poor spatial
      resolution, severe partial volume effect, and the ongoing maturation and
      myelination processes. During the first year of life, the brain image contrast
      between white and gray matters undergoes dramatic changes. In particular, the
      image contrast inverses around 6-8months of age, where the white and gray matter
      tissues are isointense in T1 and T2 weighted images and hence exhibit the
      extremely low tissue contrast, posing significant challenges for automated
      segmentation. In this paper, we propose a general framework that adopts sparse
      representation to fuse the multi-modality image information and further
      incorporate the anatomical constraints for brain tissue segmentation.
      Specifically, we first derive an initial segmentation from a library of aligned
      images with ground-truth segmentations by using sparse representation in a patch
      based fashion for the multi-modality T1, T2 and FA images. The segmentation
      result is further iteratively refined by integration of the anatomical
      constraint. The proposed method was evaluated on 22 infant brain MR images
      acquired at around 6months of age by using a leave-one-out cross-validation, as
      well as other 10 unseen testing subjects. Our method achieved a high accuracy for
      the Dice ratios that measure the volume overlap between automated and manual
      segmentations, i.e., 0.889+/-0.008 for white matter and 0.870+/-0.006 for gray
      matter. 

PMID- 24291617
TI  - Epidemiology of community-acquired bacteremia among infants in a medical center
      in Taiwan, 2002-2011.
AB  - OBJECTIVE: To investigate the etiologies and antibiotic susceptibility of
      community-acquired bacteremia in infants in a medical center in northern Taiwan.
      METHODS: We conducted a retrospective analysis of all blood cultures from infants
      in the National Taiwan University Hospital from 2002 to 2011 to find community
      acquired bacteremia. Common pathogens, antibiotic resistance, and outcome were
      analyzed. RESULTS: During the study period, 25,628 blood cultures were collected,
      and 3.4% of the cultures were positive, of which 15.9% were categorized as
      community-acquired bacteremia. In the age group of 0-6-days, the leading
      causative organisms were group B streptococcus (41.7%) and Escherichia coli
      (30.6%). In the 7-90-days and 4-6-months groups, the most common pathogens were
      E. coli (44.1%, 45.5%, respectively) and group B streptococcus (32.4%, 13.6%,
      respectively). For infants aged 7-12 months, the most common pathogens were
      Salmonella species (51.1%) and E. coli (12.8%). The overall mortality rate of
      community-acquired bacteremia was 6%. Urinary tract infection was the concomitant
      diagnosis among 52.4% of infants with E. coli bacteremia. Meningitis was found in
      33.3% of infants with group B streptococcus bacteremia. Listeria monocytogenes
      bacteremia was identified in three infants, one of whom had meningitis.
      Penicillin resistance was found in 4% of group B streptococcus and ampicillin
      resistance in 71% of E. coli. CONCLUSION: Our study provides updated etiological
      data on community-acquired bacteremia in infants in northern Taiwan. Group B
      streptococcus and E. coli remained the leading pathogens in infants aged 6 months
      or younger and Salmonella species for those older than 6 months.

PMID- 24291618
TI  - Proton pump inhibitor usage and the associated risk of pneumonia in patients with
      chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a serious medical problem and public
      health issue in Taiwan. Gastrointestinal symptoms frequently occur in patients
      with CKD, and proton pump inhibitors (PPIs) have therapeutic indications for
      gastrointestinal disorders involving excessive acid production. However, PPIs may
      also increase the risk of developing pneumonia through acute and irreversible
      gastric acid suppression. This study aimed to characterize differences in the
      risk of pneumonia in patients with CKD who use PPIs. METHODS: This population
      based case-control cohort study in Taiwan collected data from the Taiwan Health
      Insurance Research Database. Cases studied consisted of all patients in the
      database with an initial diagnosis of CKD during the 5-year period from 1997 to
      2002. Each patient with CKD who used PPIs during this 5-year period was tracked
      to identify the occurrence of any type of pneumonia. We estimated the adjusted
      hazard ratios (HRs) and 95% confidence interval (95% CI) by using multiple
      logistic regression analysis. RESULTS: The adjusted HR of the risk of pneumonia
      for patients with CKD using PPIs was 2.21 (95% CI = 1.59-3.07, p < 0.001). The
      risk of pneumonia was found to be positively associated with administration of
      PPIs. We observed a greater risk of pneumonia in patients with CKD using PPIs
      than in patients not using PPIs. CONCLUSION: Results of this study suggest that
      use of PPIs in CKD patients may be associated with increasing the risk of
      pneumonia. Physicians should exercise caution while prescribing PPIs for patients
      with CKD.

PMID- 24291619
TI  - Clinical and microbiological characteristics of peritoneal dialysis-related
      peritonitis caused by Klebsiella pneumoniae in southern Taiwan.
AB  - BACKGROUND/PURPOSE(S): Gram-negative peritonitis is a frequent and serious
      complication of peritoneal dialysis (PD). No previous reports have focused on
      Klebsiella pneumoniae infection. The aim of this study was to investigate the
      host and bacterial factors associated with K. pneumoniae PD-related peritonitis.
      METHODS: We retrospectively studied K. pneumoniae PD-peritonitis cases treated at
      a university hospital in southern Taiwan during 1990-2011, and analyzed the
      clinical features and outcomes and bacterial characteristics of serotypes,
      hypermucoviscosity (HV), and virulence-associated genes such as wabG, uge, and
      rmpA in K. pneumoniae PD-related peritonitis. Fifty-four isolates of K.
      pneumoniae-related community-acquired urinary tract infection (UTI) and 76
      morphologically different nonpathogenic K. pneumoniae isolates from healthy
      adults were used as controls. RESULTS: K. pneumoniae was the second most common
      monomicrobial pathogen causing Gram-negative PD-related peritonitis (n = 13,
      2.7%), and the most common pathogen involved in polymicrobial peritonitis (16/43,
      37.2%) and associated with high catheter removal rate (7/16, 43.8%). Compared
      with Escherichia coli peritonitis cases, patients with monomicrobial K.
      pneumoniae peritonitis also had insignificantly higher incidence of
      sepsis/bacteremia [n = 5 (38%), p = 0.11] and a higher mortality rate [n = 3
      (23%), p = 0.36]. The prevalence of K1/K2 (n = 1, 7.7%) serotypes was low, but
      there was a higher prevalence of serotype K20 (n = 3, 23.1%) in K. pneumoniae
      isolates derived from monomicrobial PD-related peritonitis compared with control
      groups. HV phenotype (p < 0.001) and rmpA genotype (p = 0.007) were absent in the
      peritonitis group. CONCLUSION: This is the first study focused on clinical and
      microbiological characteristics of K. pneumoniae PD-related peritonitis. K.
      pneumoniae was a common Gram-negative pathogen causing monomicrobial and
      polymicrobial PD-related peritonitis in southern Taiwan. The bacterial
      characteristics with low percentage of capsular serotype K1/K2, no significant
      HV, and absence of rmpA suggest a different pathogenesis in K. pneumoniae PD
      related peritonitis compared with that in UTI and liver abscess.

PMID- 24291620
TI  - Multidimensional nature of caregiving: translating research into everyday
      practice.

PMID- 24291621
TI  - Re-examining the role of high-dose chemotherapy in the treatment of light chain
      amyloidosis.

PMID- 24291622
TI  - Utility of positron annihilation lifetime technique for the assessment of
      spectroscopic data of some charge-transfer complexes derived from N-(1
      Naphthyl)ethylenediamine dihydrochloride.
AB  - In this work, structural, thermal, morphological, pharmacological screening and
      positron annihilation lifetime measurements were performed on the interactions
      between a N-(1-Naphthyl)ethylenediamine dihydrochloride (NEDA.2HCl) donor and
      three types of acceptors to characterize these CT complexes. The three types of
      acceptors include pi-acceptors (quinol and picric acid), sigma-acceptors (iodine)
      and vacant orbital acceptors (tin(IV) tetrachloride and zinc chloride). The
      positron annihilation lifetime parameters were found to be dependent on the
      structure, electronic configuration, the power of acceptors and molecular weight
      of the CT complexes. The positron annihilation lifetime spectroscopy can be used
      as a probe for the formation of charge-transfer (CT) complexes. 

PMID- 24291623
TI  - Investigation of the effects of Zn2+, Ca2+ and Na+ ions on the interaction
      between zonisamide and human serum albumin (HSA) by spectroscopic methods.
AB  - In this work, The effect of three metal ions Zn(2+), Ca(2+) and Na(1+) on the
      interaction between human serum albumin (HSA) and zonisamide (ZNS) was
      investigated employing fluorescence, ultraviolet-visible (UV-Vis) absorption and
      circular dichroism (CD) under simulated physiological conditions. Fluorescence
      spectroscopy revealed that these metallic ions and ZNS can quench the HSA
      fluorescence, and this quenching effect became more significant when both ion and
      drug are present together. It was found that the quenching mechanism is a
      combination of static quenching with nonradiative energy transfer. The binding
      sites number (n), the binding constant (Kb) and the spatial-distance (r) of ZNS
      with HSA without or with Zn(2+), Ca(2+) and Na(1+) ions were calculated. The
      presence of Ca(2+) and Na(+) ions decreased the binding constants (Kb) and the
      number of binding sites (n) of ZNS-HSA complex. However, the presence of Zn(2+)
      increased the affinity of ZNS for HSA largely. Changes in UV-Vis absorption and
      CD data are due to the microenvironment of amide moieties in HSA molecules. 

PMID- 24291624
TI  - Moganite in selected Polish chert samples: the evidence from MIR, Raman and X-ray
      studies.
AB  - The authors discuss the results of structural investigations (XRD, MIR, Raman) of
      Polish cherts from different geological formations. The X-ray diffraction
      analyses explicitly confirmed the presence of moganite, which was identified on
      the basis of satellite XRD peaks positioned/occurring close to the quartz
      reflections and the additional reflections with the dhkl values 4.456 and 3.101
      A, and established its amounts as varying between about 1 and above 17 wt%. The
      mid-infrared and Raman spectroscopy also proved the presence of moganite,
      indicated by the 695 and 560-555 cm(-)(1) bands, respectively. These analytical
      finds allow to identify moganite in samples containing various SiO2 polymorphs.

PMID- 24291625
TI  - Meta-analysis of the effect of strengthening interventions in individuals with
      cerebral palsy.
AB  - This study aimed to investigate the evidence that strengthening interventions can
      improve muscle strength and activity in individuals with cerebral palsy. The
      search focused on studies that employed strength training for children with
      cerebral palsy for which six electronic databases were used to extract literature
      published from 2001 to 2012. The key terms used in these searches were combined
      strength training, strengthening, weight training, weight lifting, resistance,
      and cerebral palsy. The quality of each study was assessed using the PEDro
      (Physiotherapy Evidence Database) scale. Thirteen randomized controlled trial
      studies were selected and divided into categories according to program type,
      mode, and outcome measures. The overall effect sizes of each study and types of
      strengthening were large. Strengthening exercise improved muscle strength to a
      greater degree, when practiced 3 times per week in 40-50 min sessions than in
      other categories of session length, and greater improvement was observed in
      younger children than in older. The effect size of the activities and variables
      related to gait, except for gait endurance, were medium to large. The effect size
      of individual muscles was large, but the effect sizes for ankle plantar flexor,
      hip abductor/adductor, and extensor were insignificant. Strengthening
      interventions are useful for increasing muscle strength in individuals with
      cerebral palsy, specifically in youth and children, and optimal exercise
      consisted of 40- to 50-min sessions performed 3 times per week. Although
      strengthening interventions may improve activities, including gait, more studies
      that are rigorous are needed to determine the contributions to gross motor
      function.

PMID- 24291626
TI  - Integrated earth system dynamic modeling for life cycle impact assessment of
      ecosystem services.
AB  - Despite the increasing awareness of our dependence on Ecosystem Services (ES),
      Life Cycle Impact Assessment (LCIA) does not explicitly and fully assess the
      damages caused by human activities on ES generation. Recent improvements in LCIA
      focus on specific cause-effect chains, mainly related to land use changes,
      leading to Characterization Factors (CFs) at the midpoint assessment level.
      However, despite the complexity and temporal dynamics of ES, current LCIA
      approaches consider the environmental mechanisms underneath ES to be independent
      from each other and devoid of dynamic character, leading to constant CFs whose
      representativeness is debatable. This paper takes a step forward and is aimed at
      demonstrating the feasibility of using an integrated earth system dynamic
      modeling perspective to retrieve time- and scenario-dependent CFs that consider
      the complex interlinkages between natural processes delivering ES. The GUMBO
      (Global Unified Metamodel of the Biosphere) model is used to quantify changes in
      ES production in physical terms - leading to midpoint CFs - and changes in human
      welfare indicators, which are considered here as endpoint CFs. The interpretation
      of the obtained results highlights the key methodological challenges to be solved
      to consider this approach as a robust alternative to the mainstream rationale
      currently adopted in LCIA. Further research should focus on increasing the
      granularity of environmental interventions in the modeling tools to match current
      standards in LCA and on adapting the conceptual approach to a spatially-explicit
      integrated model. 

PMID- 24291627
TI  - Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal
      care products from reclaimed water onto/from a natural sediment.
AB  - In the present work, the sorption of pharmaceutical and personal care products
      (PPCPs) (acetaminophen, atenolol, carbamazepine, caffeine, naproxen and
      sulphamethoxazole) onto the natural organic matter (NOM) and the inorganic
      surfaces of a natural sandy loam sediment was quantified separately. The
      quantification was based on the PPCP charge, their degree of ionisation, their
      octanol-water partitioning coefficient (KOW) and the sediment organic carbon
      fraction (fOC). PPCP desorption from the sediment was examined under conditions
      of infiltrating water containing a high concentration of inorganic ions
      (mimicking infiltrating reclaimed water), and a low concentration (and smaller
      diversity) of inorganic ions (mimicking rainwater infiltration). Batch tests were
      performed using a sediment/water ratio of 1:4 and a PPCP initial concentration
      ranging from 1 to 100 MUg L(-1). The results showed the type and degree of PPCP
      ionisation to strongly influence the sorption of these compounds onto the
      sediment. The sorption of cationic species onto the sediment was higher than that
      of anionic species and mostly reversible; the sorption of neutral species was
      negligible. The anionic species sorbed less onto the sediment, but also desorbed
      less easily. More than 70% of the total sorption was due to interaction with
      mineral surfaces. This holds especially true for cationic species (atenolol and
      caffeine) which sorption was enhanced by the negative surface charge of the
      sediment. The presence of inorganic ions had no impact on the desorption of the
      PPCPs from the sediment. According to the calculated percentages of removal, the
      mobility followed the order:
      carbamazepine>acetaminophen>naproxen>atenolol>sulfamethoxazole>caffeine.

PMID- 24291628
TI  - Development towards sustainability: how to judge past and proposed policies?
AB  - Most countries have, at least since the 1992 United Nations summit in RIO,
      adopted some vague "sustainable development" policies. The goals of such policies
      are to combine economic growth with social development, while protecting our
      fragile planetary life support system. The scientific data about the state of our
      planet, presented at the 2012 (Rio+20) summit, documented that today's human
      family lives even less sustainably than it did in 1992. The data indicate
      furthermore that the environmental impacts from our current economic activities
      are so large, that we are approaching situations where potentially controllable
      regional problems can easily lead to uncontrollable global disasters. Despite
      these obvious failures, our political global leaders and their institutions are
      continuing the same "sustainable development" policies, which are now
      supplemented by equally vague ideas about future "green economies". Assuming that
      (1) the majority of the human family, once adequately informed, wants to achieve
      a "sustainable way of life" and (2) that the "development towards sustainability"
      roadmap will be based on scientific principles, one must begin with unambiguous
      and quantifiable definitions of these goals. As will be demonstrated, the well
      known scientific method to define abstract and complex issues by their negation,
      satisfies these requirements. Following this new approach, it also becomes
      possible to decide if proposed and actual policy changes will make our way of
      life less unsustainable, and thus move us potentially into the direction of
      sustainability. Furthermore, if potentially dangerous tipping points are to be
      avoided, the transition roadmap must include some minimal speed requirements.
      Combining the negation method and the time evolution of that remaining natural
      capital in different domains, the transition speed for a "development towards
      sustainability" can be quantified at local, regional and global scales. The
      presented ideas allow us to measure the rate of natural capital depletion and the
      rate of restoration that will be required if humanity is to avoid reaching a
      sustainable future by a collapse transition. Unfortunately, the existence of
      quantifiable methods and tools in no way guarantees that they will be used in
      changing the direction of our journey. 

PMID- 24291629
TI  - Revisiting pesticide exposure and children's health: focus on China.
AB  - China is now becoming the largest consumer of pesticides worldwide. In recent
      years, there has been a heightened public awareness of pesticides and children's
      health in North America and around the world. Human epidemiological studies have
      examined the relationship of pesticide exposures with children's health such as
      neurodevelopment and cancer, and they reported less consistent results. With
      regard to this topic, however, China is still in the early stages of cross
      sectional or case-control design, and few data have been available. Furthermore,
      we have discussed several important limitations such as study design, exposure
      measurement, and developmental assessment from current literature, which should
      be interpreted with caution. We also presented the vulnerability and source of
      children's exposure to pesticides. 

PMID- 24291630
TI  - Persistence of the spores of B. thuringiensis subsp. kurstaki from Foray
      bioinsecticide in gleysol soil and on leaves.
AB  - The aim of this study was to determine how long the spores of Bacillus
      thuringiensis subsp. kurstaki HD-1 from Foray bioinsecticide persist in soil and
      on leaf surface after application of the bioinsecticide in an oak forest. Foray
      04 UL was sprayed over a 195-hectare oak forest on the Krotoszyn Plateau in
      Poland. B. thuringiensis was isolated from soil samples and tree leaves taken
      from randomly chosen sites. B. thuringiensis subsp. kurstaki HD-1 in the samples
      was identified upon clonal analysis of the cultured isolates by using the RAPD
      method. One month after Foray spraying, the number of B. thuringiensis increased
      in soil and decreased on leaf surface comparing to the number estimated two days
      after the application. The reduction in the number of B. thuringiensis was noted
      six months after the pesticide application and the number was decreasing during
      the following months. No B. thuringiensis was noted on leaf surface one year
      after Foray spraying and in soil after one and a half years. The study showed
      that B. thuringiensis spores from biopesticide can survive in the forest
      environment; however, relatively short persistence time does not pose
      environmental risk.

PMID- 24291631
TI  - Value of ecosystem hydropower service and its impact on the payment for ecosystem
      services.
AB  - Hydropower is an important service provided by ecosystems. We surveyed all the
      hydropower plants in the Zagunao River Basin, Southwest China. Then, we assessed
      the hydropower service by using the InVEST (The Integrated Value and Tradeoff of
      Ecosystem Service Tools) model. Finally, we discussed the impact on ecological
      compensation. The results showed that: 1) hydropower service value of ecosystems
      in the Zagunao River Basin is 216.29 Euro/hm(2) on the average, of which the high
      value area with more than 475.65 Euro/hm(2) is about 750.37 km(2), accounting for
      16.12% of the whole watershed, but it provides 53.47% of the whole watershed
      service value; 2) ecosystem is an ecological reservoir with a great regulation
      capacity. Dams cannot completely replace the reservoir water conservation
      function of ecosystems, and has high economic and environmental costs that must
      be paid as well. Compensation for water conservation services should become an
      important basis for ecological compensation of hydropower development. 3) In the
      current PES cases, the standard of compensation is generally low. Cascade
      development makes the value of upstream ecosystem services become more prominent,
      reflecting the differential rent value, and the value of ecosystem services
      should be based on the distribution of differentiated ecological compensation.

PMID- 24291632
TI  - Sclerotium rolfsii lectin exerts insecticidal activity on Spodoptera litura
      larvae by binding to membrane proteins of midgut epithelial cells and triggering
      caspase-3-dependent apoptosis.
AB  - The insect pest Spodoptera litura is considered a major threat to many
      economically important food and commercial crops. The present study establishes
      the toxic effects of Sclerotium rolfsii lectin (SRL) against S. litura larvae fed
      an artificial diet containing the purified lectin. The toxicity of SRL, as
      determined by feeding assays using different concentrations of the lectin, showed
      marginal effects on larval growth but a remarkable mortality rate of 68.52 +/-
      8.48% at the highest lectin concentration, 0.06% (600 MUg/g), with an LC50 value
      of 430 MUg/g of artificial diet. SRL is resistant to proteolysis by larval gut
      proteases even after 24-h incubation. Histochemical studies and western blot
      analyses of lectin binding revealed the interaction of the lectin with specific
      membrane glycoproteins on epithelial cells of the midgut. Identification of SRL
      interacting midgut membrane proteins using lectin affinity chromatography and ESI
      Q-TOF analysis revealed the involvement of these proteins in immunomodulatory
      responses in insects. Active caspase-3-like activity and DNA fragmentation
      observed in the midgut epithelial cells of larvae fed a lectin-containing diet
      supported the mechanism of apoptosis-induced death. These findings suggested that
      SRL can be a valuable tool in plant biotechnology for developing insect-resistant
      transgenic crops.

PMID- 24291633
TI  - Impact of elevated pCO2 on paralytic shellfish poisoning toxin content and
      composition in Alexandrium tamarense.
AB  - Ocean acidification is considered a major threat to marine ecosystems and may
      particularly affect primary producers. Here we investigated the impact of
      elevated pCO2 on paralytic shellfish poisoning toxin (PST) content and
      composition in two strains of Alexandrium tamarense, Alex5 and Alex2. Experiments
      were carried out as dilute batch to keep carbonate chemistry unaltered over time.
      We observed only minor changes with respect to growth and elemental composition
      in response to elevated pCO2. For both strains, the cellular PST content, and in
      particular the associated cellular toxicity, was lower in the high CO2
      treatments. In addition, Alex5 showed a shift in its PST composition from a non
      sulfated analogue towards less toxic sulfated analogues with increasing pCO2.
      Transcriptomic analyses suggest that the ability of A. tamarense to maintain
      cellular homeostasis is predominantly regulated on the post-translational level
      rather than on the transcriptomic level. Furthermore, genes associated to
      secondary metabolite and amino acid metabolism in Alex5 were down-regulated in
      the high CO2 treatment, which may explain the lower PST content. Elevated pCO2
      also induced up-regulation of a putative sulfotransferase sxtN homologue and a
      substantial down-regulation of several sulfatases. Such changes in sulfur
      metabolism may explain the shift in PST composition towards more sulfated
      analogues. All in all, our results indicate that elevated pCO2 will have minor
      consequences for growth and elemental composition, but may potentially reduce the
      cellular toxicity of A. tamarense.

PMID- 24291634
TI  - Histopathological and immunohistochemical analysis of Tilapia (Oreochromis
      niloticus) exposed to cylindrospermopsin and the effectiveness of N
      Acetylcysteine to prevent its toxic effects.
AB  - Cylindrospermopsin (CYN) is a cytotoxic cyanotoxin produced by several
      cyanobacteria species. It has been demonstrated that CYN is a potent protein and
      glutathione synthesis inhibitor, and induces genotoxicity and oxidative stress.
      The present study investigated the protective role of two different doses of N
      Acetylcysteine (NAC) (22 and 45 mg/fish/day) against the pathological changes
      induced in tilapia (Oreochromis niloticus) orally exposed to a single dose of
      pure CYN or CYN from an Aphanizomenon ovalisporum CYN-producer strain (200 MUg/kg
      of CYN in both cases). Moreover, an immunohistochemical (IHC) analysis was
      carried out in order to elucidate the CYN distribution in exposed fish. The
      histological findings were more pronounced when fish were intoxicated with CYN
      from the cyanobacterial strain, being liver and kidney the main targets for CYN
      toxicity. NAC pre-treatment was effective reducing the damage induced by CYN,
      especially at the highest dose employed (45 mg/fish/day), with a total prevention
      in all organs. The IHC analysis showed that CYN-antigen appeared mainly in the
      liver and gastrointestinal tract, although it was also present in kidney and
      gills. In this case, the immunopositive results were more abundant in those fish
      exposed to pure CYN. NAC reduced the number of immunopositive cases in a dose
      dependent way. Therefore, NAC can be considered a useful chemoprotectant in the
      prophylaxis and treatment of CYN-related intoxications in fish. 

PMID- 24291636
TI  - Melatonin and its atheroprotective effects: a review.
AB  - Atherosclerosis is a chronic vascular disease in which oxidative stress and
      inflammation are commonly implicated as major causative factors. Identification
      of novel strategies that contribute to plaque stabilization or inhibition
      represents a continuing challenge for the medical community. The evidence from
      the last decade highlights that melatonin influences the cardiovascular system,
      but its mechanisms of action have not been definitively clarified. Melatonin has
      atheroprotective effects by acting on different pathogenic signaling processes;
      these result from its direct free radical scavenger activity, its indirect
      antioxidant properties and its anti-inflammatory actions. In this review, we
      summarize the many pieces of the puzzle which identified molecular targets for
      prevention and therapy against the atherosclerotic pathogenic processes and we
      evaluate the data documenting that melatonin treatment has important actions that
      protect against atherosclerosis and atherosclerosis-related cardiovascular
      diseases. 

PMID- 24291635
TI  - Hypo-glycosylated human follicle-stimulating hormone (hFSH(21/18)) is much more
      active in vitro than fully-glycosylated hFSH (hFSH(24)).
AB  - Hypo-glycosylated hFSH(21/18) (possesses FSHbeta(21) and FSHbeta(18)bands) was
      isolated from hLH preparations by immunoaffinity chromatography followed by gel
      filtration. Fully-glycosylated hFSH(24) was prepared by combining the fully
      glycosylated FSHbeta(24) variant with hCGalpha and isolating the heterodimer. The
      hFSH(21/18) glycoform preparation was significantly smaller than the hFSH(24)
      preparation and possessed 60% oligomannose glycans, which is unusual for hFSH.
      Hypo-glycosylated hFSH(21/18) was 9- to 26-fold more active than fully
      glycosylated hFSH(24) in FSH radioligand assays. Significantly greater binding of
      (125)I-hFSH(21/18) tracer than hFSH(24) tracer was observed in all competitive
      binding assays. In addition, higher binding of hFSH(21/18) was noted in
      association and saturation binding assays, in which twice as much hFSH(21/18) was
      bound as hFSH(24). This suggests that more ligand binding sites are available to
      hFSH(21/18) in FSHR than to hFSH(24). Hypo-glycosylated hFSH(21/18) also bound
      rat FSHRs more rapidly, exhibiting almost no lag in binding, whereas hFSH(24)
      specific binding proceeded very slowly for almost the first hour of incubation. 

PMID- 24291637
TI  - The flavonoid chrysin, an endocrine disrupter, relaxes cholecystokinin- and KCl
      induced tension in male guinea pig gallbladder strips through multiple signaling
      pathways.
AB  - The bioflavonoids have effects on vascular smooth muscle and gastrointestinal
      smooth muscle. The flavone and phytoestrogen, chrysin, has been shown to have a
      vasorelaxant effect on resistance blood vessels. This effect was mediated by
      nitric oxide (NO). Chrysin inhibited aromatase/estrogen biosynthesis in
      postmenopausal women. The purpose of this study was to determine if chrysin had
      an effect on cholecystokinin- or KCl-induced tension in male guinea pig
      gallbladder strips. In addition, the second messenger(s) system(s) that mediated
      the effect were to be determined. A pharmacologic approach was used. Male guinea
      pig gallbladder strips were placed in in vitro chambers filled with Krebs
      solution, maintained at 37  degrees C, and gassed with 95% O2-5% CO2. Changes in
      tension were recorded using a polygraph. It was shown that the PKA/cAMP second
      messenger system mediated part of the observed chrysin-induced relaxation of
      cholecystokinin-induced tension, the PKC system also mediated part of the
      relaxation, and the inhibition of both extracellular Ca(2+) entry and
      intracellular Ca(2+) release also mediated the chrysin-induced relaxation. This
      is the first report of chrysin having an effect on gallbladder smooth muscle
      contraction.

PMID- 24291638
TI  - Regulation of the neuronal transcription factor NPAS4 by REST and microRNAs.
AB  - NPAS4 is a brain restricted, activity-induced transcription factor which
      regulates the expression of inhibitory synapse genes to control homeostatic
      excitatory/inhibitory balance in neurons. NPAS4 is required for normal social
      interaction and contextual memory formation in mice. Protein and mRNA expression
      of NPAS4 is tightly coupled to neuronal depolarization and most prevalent in the
      cortical and hippocampal regions in the brain, however the precise mechanisms by
      which the NPAS4 gene is controlled remain unexplored. Here we show that
      expression of NPAS4 mRNA is actively repressed by RE-1 silencing transcription
      factor/neuron-restrictive silencer factor (REST/NRSF) in embryonic stem cells and
      non-neuronal cells by binding multiple sites within the promoter and Intron I of
      NPAS4. Repression by REST also appears to correlate with the binding of the zinc
      finger DNA binding protein CTCF within Intron I of NPAS4. In addition, we show
      that the 3' untranslated region (3'UTR) of NPAS4 can be targeted by two
      microRNAs, miR-203 and miR-224 to further regulate its expression. miR-224 is a
      midbrain/hypothalamus enriched microRNA which is expressed from an intron within
      the GABAA receptor epsilon (GABRE) gene and may further regionalize NPAS4
      expression. Our results reveal REST and microRNA dependent mechanisms that
      restrict NPAS4 expression to the brain. 

PMID- 24291639
TI  - COX-2 is involved in ET-1-induced hypertrophy of neonatal rat cardiomyocytes:
      role of NFATc3.
AB  - Endothelin-1 (ET-1) is a critical molecule that involved in heart failure. It has
      been proved that ET-1 stimulation results in cardiac hypertrophy both in vitro
      and in vivo, but the mechanisms underlying remain largely unknown. In this study,
      we reported that cyclooxygenase-2 (COX-2) might be an important mediator of
      hypertrophic responses to ET-1 stimulation. In the cultured rat neonatal
      cardiomyocytes, ET-1 significantly upregulated the expression and activity of COX
      2, which was accompanied by increase in cell surface area and BNP mRNA level. In
      contrast, ET-1-dependent cardiomyocyte hypertrophy was abolished by COX-2
      selective inhibitors, NS-398 and celecoxib, or by COX-2 RNA interference, but the
      inhibitory effects could be diminished by pretreatment with PGE2. Furthermore,
      cyclosporin A (CsA) and knockdown of nuclear factor of activated T-cells c3
      (NFATc3) inhibited the expression of COX-2 induced by ET-1, and NFATc3 could also
      bound to the -GGAAA- sequence in the promoter region of rat COX-2 gene,
      indicating that calcineurin/NFATc3 signaling participated in the transcriptional
      regulation of COX-2 following ET-1 treatment. These findings provided further
      insight into the roles of ET-1 in cardiac hypertrophy and suggested a potential
      therapeutic strategy against cardiac hypertrophy by inhibiting COX-2. 

PMID- 24291640
TI  - Kras gene codon 12 mutation detection enabled by gold nanoparticles conducted in
      a nanobioarray chip.
AB  - This study employs a nanobioarray (NBA) chip for multiple biodetection of single
      base pair mutations at the Kras gene codon 12. To distinguish between the mutant
      and wild-type target DNAs, current bioarray methods use high-temperature
      hybridization of the targets to the allele-specific probes. However, these
      techniques need prior temperature optimization and become harder to implement in
      the case of the detection of multiple mutations. We aimed to detect these
      mutations at a single temperature (room temperature), enabled by the use of gold
      nanoparticles (AuNPs) on the bioarray created within nanofluidic channels. In
      this method, a low amount of target oligonucleotides (5fmol) and polymerase chain
      reaction (PCR) products (300pg) were first loaded on the AuNP surface, and then
      these AuNP-bound targets were introduced into the channels of a
      polydimethylsiloxane (PDMS) glass chip. The targets hybridized to their
      complementary probes at the intersection of the target channels to the pre
      printed oligonucleotide probe lines on the glass surface, creating a bioarray.
      Using this technique, fast and high-throughput multiple discrimination of the
      Kras gene codon 12 were achieved at room temperature using the NBA chip, and the
      specificity of the method was proved to be as high as that with the temperature
      stringency method. 

PMID- 24291641
TI  - Cell disruption using a different methodology for proteomics analysis of
      Trypanosoma cruzi strains.
AB  - We have developed a cell disruption method to produce a protein extract using
      Trypanosoma cruzi cells based on a straightforward hypoosmotic lysis protocol.
      The procedure consists of three steps: incubation of the cells in a hypoosmotic
      lysis buffer, sonication in a water bath, and centrifugation. The final protein
      extract was designated TcS12. The stages of cell disruption at different
      incubation times were monitored by differential interference contrast microscopy.
      After 30min of incubation in lysis buffer at 4 degrees C, the T. cruzi
      epimastigote forms changed from slender to round-shaped parasites. Nevertheless,
      cell disruption took place following sonication of the sample for 30min. The
      efficiency of the methodology was also validated by flow cytometry, which
      resulted in 72% of propidium iodide (PI)-labeled cells. To estimate the protein
      extraction yield and the differential protein expression, the proteomics profile
      of four T. cruzi strains (CL-Brener, Dm28c, Y, and 4167) were analyzed by liquid
      chromatography tandem mass spectrometry (LCMS/MS) on a SYNAPT HDMS system using
      the label-free MS(E) approach. ProteinLynx Global Server (version 2.5) with
      Expression(E) analysis identified a total of 1153 proteins and revealed 428
      differentially expressed proteins among the strains. Gene ontology analysis
      showed that not only cytosolic proteins but also nuclear and organellar ones were
      present in the extract. 

PMID- 24291642
TI  - Studying forkhead box protein A1-DNA interaction and ligand inhibition using gold
      nanoparticles, electrophoretic mobility shift assay, and fluorescence anisotropy.
AB  - Forkhead box protein 1 (FoxA1) is a member of the forkhead family of winged helix
      transcription factors that plays pivotal roles in the development and
      differentiation of multiple organs and in the regulation of estrogen-stimulated
      genes. Conventional analytical methods-electrophoretic mobility shift assay
      (EMSA) and fluorescence anisotropy (FA)-as well as a gold nanoparticles (AuNPs)
      based assay were used to study DNA binding properties of FoxA1 and ligand
      interruption of FoxA1-DNA binding. In the AuNPs assay, the distinct ability of
      protein-DNA complex to protect AuNPs against salt-induced aggregation was
      exploited to screen sequence selectivity and determine the binding affinity
      constant based on AuNPs color change and absorbance spectrum shift. Both
      conventional EMSA and FA and the AuNPs assay suggested that FoxA1 binds to DNA in
      a core sequence-dependent manner and the flanking sequence also played a role to
      influence the affinity. The EMSA and AuNPs were found to be more sensitive than
      FA in differentiation of sequence-dependent affinity. With the addition of a spin
      filtration step, AuNPs assay has been extended for studying small molecular
      ligand inhibition of FoxA1-DNA interactions enabling drug screening. The results
      correlate very well with those obtained using FA. 

PMID- 24291643
TI  - Pathogen detection by core-shell type aptamer-magnetic preconcentration coupled
      to real-time PCR.
AB  - The presence of pathogenic bacteria is a major health risk factor in food samples
      and the commercial food supply chain is susceptible to bacterial contamination.
      Thus, rapid and sensitive identification methods are in demand for the food
      industry. Quantitative polymerase chain reaction (PCR) is one of the reliable
      specific methods with reasonably fast assay times. However, many constituents in
      food samples interfere with PCR, resulting in false results and thus hindering
      the usability of the method. Therefore, we aimed to develop an aptamer-based
      magnetic separation system as a sample preparation method for subsequent
      identification and quantification of the contaminant bacteria by real-time PCR.
      To achieve this goal, magnetic beads were prepared via suspension polymerization
      and grafted with glycidylmethacrylate (GMA) brushes that were modified into high
      quantities of amino groups. The magnetic beads were decorated with two different
      aptamer sequences binding specifically to Escherichia coli or Salmonella
      typhimurium. The results showed that even 1.0% milk inhibited PCR, but our
      magnetic affinity system capture of bacteria from 100% milk samples allowed
      accurate determination of bacterial contamination at less than 2.0 h with limit
      of detection around 100 CFU/mL for both bacteria in spiked-milk samples.

PMID- 24291644
TI  - cis-Prenyltransferase atCPT6 produces a family of very short-chain
      polyisoprenoids in planta.
AB  - cis-Prenyltransferases (CPTs) comprise numerous enzymes synthesizing isoprenoid
      hydrocarbon skeleton with isoprenoid units in the cis (Z) configuration. The
      chain-length specificity of a particular plant CPT is in most cases unknown
      despite thecomposition of the accumulated isoprenoids in the tissue of interest
      being well established. In this report AtCPT6, one of the nine Arabidopsis
      thaliana CPTs, is shown to catalyze the synthesis of a family of very short-chain
      polyisoprenoid alcohols of six, seven, and eight isoprenoid units, those of seven
      units dominating The product specificity of AtCPT6 was established in vivo
      following its expression in the heterologous system of the yeast Saccharomyces
      cerevisiae and was confirmed by the absence of specific products in AtCPT6 T-DNA
      insertion mutants and their overaccumulation in AtCPT6-overexpressing plants.
      These observations are additionally validated in silico using an AtCPT6 model
      obtained by homology modeling. AtCPT6 only partially complements the function of
      the yeast homologue of CPT-Rer2 since it restores the growth but not protein
      glycosylation in rer2delta yeast.This is the first in planta characterization of
      specific products of a plant CPT producing polyisoprenoids. Their distribution
      suggests that a joint activity of several CPTs is required to produce the complex
      mixture of polyisoprenoid alcohols found in Arabidopsis roots.

PMID- 24291645
TI  - Multiple cysteine residues are necessary for sorting and transport activity of
      the arsenite permease Acr3p from Saccharomyces cerevisiae.
AB  - The yeast transporter Acr3p is a low affinity As(III)/H(+) and Sb(III)/H(+)
      antiporter located in the plasma membrane. It has been shown for bacterial Acr3
      proteins that just a single cysteine residue, which is located in the middle of
      the fourth transmembrane region and conserved in all members of the Acr3 family,
      is essential for As(III) transport activity. Here, we report a systematic
      mutational analysis of all nine cysteine residues present in the Saccharomyces
      cerevisiae Acr3p. We found that mutagenesis of highly conserved Cys151 resulted
      in a complete loss of metalloid transport function. In addition, lack of Cys90
      and Cys169, which are conserved in eukaryotic members of Acr3 family, impaired
      Acr3p trafficking to the plasma membrane and greatly reduced As(III) efflux,
      respectively. Mutagenesis of five other cysteines in Acr3p resulted in moderate
      reduction of As(III) transport capacities and sorting perturbations. Our data
      suggest that interaction of As(III) with multiple thiol groups in the yeast Acr3p
      may facilitate As(III) translocation across the plasma membrane. 

PMID- 24291646
TI  - Hyperbaric oxygen promotes osteogenic differentiation of bone marrow stromal
      cells by regulating Wnt3a/beta-catenin signaling--an in vitro and in vivo study.
AB  - We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is
      increased via osteogenic differentiation of bone marrow stromal cells (BMSCs),
      which is regulated by Wnt3a/beta-catenin signaling. Our in vitro data showed that
      HBO increased cell proliferation, Wnt3a production, LRP6 phosphorylation, and
      cyclin D1 expression in osteogenically differentiated BMSCs. The mRNA and protein
      levels of Wnt3a, beta-catenin, and Runx2 were upregulated while those of GSK
      3beta were downregulated after HBO treatment. The relative density ratio (phospho
      protein/protein) of Akt and GSK-3beta was both up-regulated while that of beta
      catenin was down-regulated after HBO treatment. We next investigated whether HBO
      affects the accumulation of beta-catenin. Our Western blot analysis showed
      increased levels of translocated beta-catenin that stimulated the expression of
      target genes after HBO treatment. HBO increased TCF-dependent transcription,
      Runx2 promoter/Luc gene activity, and the expression of osteogenic markers of
      BMSCs, such as alkaline phosphatase activity, type I collagen, osteocalcin,
      calcium, and the intensity of Alizarin Red staining. HBO dose dependently
      increased the bone morphogenetic protein (BMP2) and osterix production. We
      further demonstrated that HBO increased the expression of vacuolar-ATPases, which
      stimulated Wnt3a secretion from BMSCs. Finally, we showed that the beneficial
      effects of HBO on bone formation were related to Wnt3a/beta-catenin signaling in
      a rabbit model by histology, mechanical testing, and immunohistochemical assays.
      Accordingly, we concluded that HBO increased the osteogenic differentiation of
      BMSCs by regulating Wnt3a secretion and signaling. 

PMID- 24291647
TI  - Neural mechanisms of female sexual behavior in the rat; comparison with male
      ejaculatory control.
AB  - The sequential organization of sexual behavior of the female rat is described,
      eventually leading to the lordotic posture, shown during mating. A complex set of
      signals: olfactory, cutaneous sensory as well as genitosensory, is guiding the
      female to this specific posture, eventually. Genitosensory signals converge in
      the lumbosacral levels of the spinal cord, from where they are dispersed to a
      series of supraspinal brain areas, in the brainstem, thalamus, hypothalamus and
      limbic system. The similarity with the neural activation patterns observed in the
      male rat is remarkable. In a number of brain areas, however: the midbrain
      periaqueductal gray, the ventrolateral part of the ventromedial hypothalamic
      nucleus (VMHvl) and the medial preoptic-lateral septum regions, specific male
      female differences have been observed. Especially the VMHvl is an intriguing
      area, as it has been shown that the same neurons may be involved in 'opposite
      behavior' like aggression and the induction of lordosis. The motor mechanisms
      controlling the lordosis posture in the rat as well as in some other mammals are
      discussed, as well as some aspects of the reward mechanisms contributing to
      female sex. We conclude that we have collected a great amount of
      neurophysiological knowledge over the last 20 years, but that the unresolved
      questions are still numerous. In this field, there is still much to explore.

PMID- 24291648
TI  - Treatment of erectile dysfunction: new targets and strategies from recent
      research.
AB  - In recent years, research on penile erection has increasingly been centered on
      the molecular mechanisms involved. Major progress has been made in the field and
      at present a whole number of neurotransmitters, chemical effectors, growth
      factors, second-messenger molecules, ions, intercellular proteins, and hormones
      have been characterized as components of the complex process of erection. This
      knowledge has led to the discovery of several new therapeutic targets and
      multiple medical approaches for the treatment of erectile dysfunction (ED). This
      review focuses on the progress made in this field within the last few years. 

PMID- 24291649
TI  - The interphase of the formalin test.
AB  - The formalin test still surprises with its biphasic pain-related behavior
      resulting from a quiescent interphase that does not occur with other algogenic
      compounds and remains unexplained. The first phase has been attributed to TRPA1
      mediated excitation of nociceptors, the second phase to their inflammatory and/or
      spinal sensitization. We show that the second and interphase require higher
      formaldehyde concentrations to emerge, and that from 12 mM on calcium influx is
      induced in TRPA1-deficient sensory neurons as well as in native HEK293T cells.
      After a short depolarizing and excitatory period in a subset, all wild-type
      neurons showed a concentration-dependent hyperpolarization, a reduction of
      voltage-activated sodium currents, and a progressive increase of the input
      resistance, which, after about 10 min restored the transiently lost excitability,
      enabling smaller and wider action potentials to be evoked than before
      formaldehyde (30 mM). The hyperpolarizing effect was absent if extracellular
      sodium was replaced, and largely prevented by a high but not low concentration of
      tetrodotoxin. In rat skin in vivo, the spatiotemporal redistribution of injected
      formalin and the plasma extravasation were studied using Evans blue. The
      parameters gained were entered into a computational model to predict the
      activation pattern of primary afferents. The model supports a peripherally
      generated biphasic response, the time course matching the behavioral results. In
      conclusion, the interphase is a result of hyperpolarization and transient
      inactivation by formaldehyde of the surviving neurons; their recovery and the
      centrifugal spread of formalin in the skin induce a second phase of nociceptive
      activity before the formalin concentration falls below threshold.

PMID- 24291650
TI  - Letter to the editor.

PMID- 24291651
TI  - Response to letter to the editor.

PMID- 24291652
TI  - Can we stop pain before it starts?

PMID- 24291653
TI  - Polybrominated diphenyl ethers in UK human milk: implications for infant exposure
      and relationship to external exposure.
AB  - Fourteen tri-deca polybrominated diphenyl ethers (PBDEs) were investigated in 35
      human milk samples from Birmingham, UK. While none of the hepta-nona BDEs (the
      main components of the octaBDE technical mixture) was above the limit of
      quantitation (LOQ); BDE-47 (average concentration=3.3ngg(-1) lipid weight (lw))
      was quantified in all samples contributing 34-74% to Sigmatri-hexa BDEs (the
      principal constituents of the pentaBDE commercial formulation). BDE-209 (the main
      congener in the decaBDE formulation) was present above the LOQ in 69% of samples
      (average concentration=0.31ngg(-1) lw). Concentrations of Sigmatri-hexa BDEs
      ranged from 0.2 to 26ngg(-1) lw with concentrations of BDE-47>BDE-153>BDE-99.
      While concentrations of Sigmatri-hexa BDEs in this study (average=5.95ngg(-1) lw)
      were at the high end of those reported from other European countries,
      concentrations of BDE-209 were lower than those reported in human milk from other
      countries. The average exposure of a UK nursing infant to Sigmatri-hexa BDEs
      (35ng (kg bw)(-1)day(-1)) via breast milk exceeded the upper-bound dietary
      intakes of both UK adults and toddlers. Using a simple one compartment
      pharmacokinetic model, PBDE intakes of UK adults via inhalation, diet and dust
      ingestion were converted to predicted body burdens. Predictions compared well
      with those observed for Sigmatri-hexa BDEs and BDE-209 in breast milk. 

PMID- 24291654
TI  - Mortality in rheumatoid arthritis: the impact of disease activity, treatment with
      glucocorticoids, TNFalpha inhibitors and rituximab.
AB  - OBJECTIVES: To investigate the impact of disease activity, the course of the
      disease, its treatment over time, comorbidities and traditional risk factors on
      survival. METHODS: Data of the German biologics register RABBIT were used. Cox
      regression was applied to investigate the impact of time-varying covariates
      (disease activity as measured by the DAS28, functional capacity, treatment with
      glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs
      (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and
      smoking. RESULTS: During 31 378 patient-years of follow-up, 463 of 8908 patients
      died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with
      persistent, highly active disease (mean DAS28  > 5.1) had a significantly higher
      mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients
      with persistently low disease activity (mean DAS28 < 3.2). Poor function and
      treatment with glucocorticoids > 5 mg/d was significantly associated with an
      increased mortality, independent of disease activity. Significantly lower
      mortality was observed in patients treated with tumour necrosis factor alpha
      (TNFalpha) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57
      (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99),
      compared to those receiving methotrexate. To account for treatment termination in
      patients at risk, an HRadj for patients ever exposed to TNFalpha inhibitors or
      rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to
      0.97). CONCLUSIONS: Patients with long-standing high disease activity are at
      substantially increased risk of mortality. Effective control of disease activity
      decreases mortality. TNFalpha inhibitors and rituximab seem to be superior to
      conventional DMARDs in reducing this risk.

PMID- 24291655
TI  - Citrullination of autoantigens implicates NETosis in the induction of
      autoimmunity.
AB  - Tolerance blocks the expression of autoantibodies, whereas autoimmunity promotes
      it. How tolerance breaks and autoantibody production begins thus are crucial
      questions for understanding and treatment of autoimmune diseases. Evidence
      implicates cell death and autoantigen modifications in the initiation of
      autoimmune reactions. One form of neutrophil cell death called NETosis deserves
      attention because it requires the post-translational modification of histones and
      results in the extracellular release of chromatin. NETosis received its name from
      NET, the acronym given to Neutrophil Extracellular Trap. The extracellular
      chromatin incorporates histones in which arginines have been converted to
      citrullines by peptidylarginine deiminase IV (PAD4). The deiminated chromatin may
      function to capture or 'trap' bacterial pathogens, thus generating an
      extracellular complex of deiminated histones and bacterial cell adjuvants. The
      complex of bacterial antigens and deiminated chromatin may be internalised by
      host phagocytes during acute inflammatory conditions, as arise during bacterial
      infections or chronic autoinflammatory disorders. The uptake and processing of
      deiminated chromatin together with bacterial adjuvants by phagocytes may induce
      the presentation of modified histone epitopes and co-stimulation, thus yielding a
      powerful stimulus to break tolerance. Autoantibodies to deiminated histones are
      prevalent in Felty's syndrome patients and are present in systemic lupus
      erythematosus (SLE) and patients with rheumatoid arthritis (RA). These
      observations clearly implicate histone deimination as an epigenetic mark that can
      act as an autoantibody stimulant. 

PMID- 24291656
TI  - Gene-body mass index interactions are associated with methotrexate toxicity in
      rheumatoid arthritis.

PMID- 24291657
TI  - Simulation of multiple personalities: a review of research comparing diagnosed
      and simulated dissociative identity disorder.
AB  - Dissociative Identity Disorder (DID) has long been surrounded by controversy due
      to disagreement about its etiology and the validity of its associated phenomena.
      Researchers have conducted studies comparing people diagnosed with DID and people
      simulating DID in order to better understand the disorder. The current research
      presents a systematic review of this DID simulation research. The literature
      consists of 20 studies and contains several replicated findings. Replicated
      differences between the groups include symptom presentation, identity
      presentation, and cognitive processing deficits. Replicated similarities between
      the groups include interidentity transfer of information as shown by measures of
      recall, recognition, and priming. Despite some consistent findings, this research
      literature is hindered by methodological flaws that reduce experimental validity.

PMID- 24291658
TI  - Phylogeny of the family Aglajidae (Pilsbry, 1895) (Heterobranchia: Cephalaspidea)
      inferred from mtDNA and nDNA.
AB  - The family Aglajidae includes several species of benthic, carnivorous
      cephalaspidean sea slugs, which generally lack a radula, have an internal shell,
      a posterior shield with short to moderate caudal lobes, and sensory cilia present
      on the head. The present study reports a phylogenetic analysis of the Aglajidae
      based on the mitochondrial genes 16S and CO1 and the nuclear gene H3, including
      160 specimens of 54 species, that confirms the monophyly of Aglajidae as well as
      most taxonomically established genera, with some exceptions. Although support
      values are low for some clades, the analysis recovered the following clades
      within the Aglajidae: Odontoglaja, Nakamigawaia, and Melanochlamys. Chelidonura
      appears to be paraphyletic and the monophyly of a Chelidonura-Navanax-Aglaja
      clade is strongly supported in the Bayesian analysis, plus three of the four
      individual gene trees (COI, COI without 3rd codon positions, 16S and H3).
      However, the relatively low levels of support in the maximum likelihood analyses
      prevent us from proposing the synonymization of Navanax and Aglaja with
      Chelidonura. Melanochlamys is the sister clade of Chelidonura+Aglaja+Navanax.
      Odontoglaja is basal to the rest of the Aglajidae, confirming previous hypotheses
      on the loss of the radula in Aglajidae. Nakamigawaia and Melanochlamys are
      monophyletic, and should be maintained as valid. The monophyly of Philinopsis is
      strongly supported in the Bayesian analysis and in three of the four individual
      gene trees. Further research on this group is necessary to further affirm the
      monophyly of Chelidonura+Aglaja+Navanax and Philinopsis. Based on the results of
      this phylogenetic analysis, a reclassification of the taxonomy of Aglajidae is
      probably necessary. Additional genes should provide more information and probably
      fully resolve this situation. The present molecular study (including ABGD species
      delineation analyses) suggests the existence of previously undetected species
      complexes that require additional study to determine the extent of undocumented
      biodiversity. 

PMID- 24291659
TI  - A comprehensive species-level molecular phylogeny of the New World blackbirds
      (Icteridae).
AB  - The New World blackbirds (Icteridae) are among the best known songbirds, serving
      as a model clade in comparative studies of morphological, ecological, and
      behavioral trait evolution. Despite wide interest in the group, as yet no
      analysis of blackbird relationships has achieved comprehensive species-level
      sampling or found robust support for most intergeneric relationships. Using
      mitochondrial gene sequences from all ~108 currently recognized species and six
      additional distinct lineages, together with strategic sampling of four nuclear
      loci and whole mitochondrial genomes, we were able to resolve most relationships
      with high confidence. Our phylogeny is consistent with the strongly-supported
      results of past studies, but it also contains many novel inferences of
      relationship, including unexpected placement of some newly-sampled taxa,
      resolution of relationships among major clades within Icteridae, and resolution
      of genus-level relationships within the largest of those clades, the grackles and
      allies. We suggest taxonomic revisions based on our results, including
      restoration of Cacicus melanicterus to the monotypic Cassiculus, merging the
      monotypic Ocyalus and Clypicterus into Cacicus, restoration of Dives
      atroviolaceus to the monotypic Ptiloxena, and naming Curaeus forbesi to a new
      genus, Anumara. Our hypothesis of blackbird phylogeny provides a foundation for
      ongoing and future evolutionary analyses of the group. 

PMID- 24291660
TI  - Extrabranchial mechanisms of systemic pH recovery in hagfish (Eptatretus
      stoutii).
AB  - This study investigates the role of branchial and extrabranchial processes in
      acid-base regulation in the Pacific Hagfish (Eptatretus stoutii). Hagfish were
      injected with one of the following solutions: acid saline (250mM HCl [pH=0.60],
      250mM NaCl), alkaline saline (250mM NaHCO3, 250mM NaCl, [pH~8.43]) or control
      saline (500mM NaCl) in order to achieve an acid/alkaline/saline load of
      6000MUmol.kg(-1). Using a custom designed hagfish compartmentalizing flux
      chamber, we partitioned flux of net acid or base equivalents and ammonia into the
      anterior (gill+skin) and posterior (skin+intestinal/renal/cloacal) components. We
      found that Pacific hagfish excrete H(+) primarily via branchial mechanisms but
      base excretion occurs through extrabranchial mechanisms located in the posterior
      region. In addition, we demonstrate that hagfish are able to excrete ammonia via
      the skin although this flux was not involved in compensation from an acid-base
      disturbance. 

PMID- 24291661
TI  - Chemical annotation of small and peptide-like molecules at the Protein Data Bank.
AB  - Over the past decade, the number of polymers and their complexes with small
      molecules in the Protein Data Bank archive (PDB) has continued to increase
      significantly. To support scientific advancements and ensure the best quality and
      completeness of the data files over the next 10 years and beyond, the Worldwide
      PDB partnership that manages the PDB archive is developing a new deposition and
      annotation system. This system focuses on efficient data capture across all
      supported experimental methods. The new deposition and annotation system is
      composed of four major modules that together support all of the processing
      requirements for a PDB entry. In this article, we describe one such module called
      the Chemical Component Annotation Tool. This tool uses information from both the
      Chemical Component Dictionary and Biologically Interesting molecule Reference
      Dictionary to aid in annotation. Benchmark studies have shown that the Chemical
      Component Annotation Tool provides significant improvements in processing
      efficiency and data quality. Database URL: http://wwpdb.org. 

PMID- 24291662
TI  - Combining a synthetic spermicide with a natural trichomonacide for safe,
      prophylactic contraception.
AB  - STUDY QUESTION: Can a specifically acting synthetic spermicide (DSE-37) be
      combined with a natural microbicide (saponins) for safe, prophylactic
      contraception? SUMMARY ANSWER: A 1:1 (w/w) combination of DSE-37 and Sapindus
      saponins can target sperm and Trichomonas vaginalis precisely without any
      noticeable off-target effects on somatic cells at effective concentrations. WHAT
      IS KNOWN ALREADY: Broad-spectrum vaginal agents like nonoxynol-9 (N-9) and
      cellulose sulfate have failed clinically as microbicides due to non-specific off
      target effects, whereas agents that specifically target retroviruses have shown
      promise in clinical trials. DSE-37 and Sapindus saponins, respectively,
      specifically target human sperm and T. vaginalis in vitro. STUDY DESIGN, SIZE,
      DURATION: A comprehensive study of efficacy and safety was undertaken using in
      vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37
      and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal
      activities of the two components. N-9, the spermicide in clinical use, served as
      reference control. Free sperm thiols were fluorescently glinted to reveal
      differences in the targets of the test agents. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: On/off-target effects were evaluated in vitro against human sperm, T.
      vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard
      assays of drug susceptibility, cell viability, flow cytometric assessment of cell
      apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The
      spermicidal effect was also recorded live and free thiols on sperm were
      fluorescently visualized using a commercial kit. In vivo contraceptive efficacy
      (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune
      labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in
      rabbits. MAIN RESULTS AND THE ROLE OF CHANCE: A 0.003% drug 'combination'
      containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline
      irreversibly immobilized 100% human sperm in ~30 s and eliminated 100% T.
      vaginalis in 24 h, without causing any detectable toxicity to human cervical
      (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003% exhibited lower
      microbicidal activity against Trichomonas but failed in spermicidal assays while
      causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The
      'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in
      rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5%
      'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations
      in epithelial lining of rabbit vagina with only minor changes in levels of
      inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33%
      animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity
      to vaginal epithelium with molecular expression of acute inflammation markers.
      LIMITATIONS, REASONS FOR CAUTION: The number of animals used for the in vivo
      efficacy study was limited by the approval of the animal ethics committee. WIDER
      IMPLICATIONS OF THE FINDINGS: Anti-Trichomonal contraceptives with specifically
      acting synthetic component and clinically-proven safe natural component may
      define a new concept in empowering women to control their fertility and
      reproductive health. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by
      CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and
      Family Welfare, Government of India (GAP0001). The funding agencies did not play
      any role in this study and none of the authors had any competing interest(s).

PMID- 24291663
TI  - An integrative view on the physiology of human early placental villi.
AB  - The placenta is an indispensable organ for intrauterine protection, development
      and growth of the embryo and fetus. It provides tight contact between mother and
      conceptus, enabling the exchange of gas, nutrients and waste products. The human
      placenta is discoidal in shape, and bears a hemo-monochorial interface as well as
      villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the
      paradoxical nature of the mother-fetus relationship in 1953, substantial
      knowledge in the domain of placental physiology has been gathered. In the present
      essay, an attempt has been made to build an integrated understanding of
      morphological dynamics, cell biology, and functional aspects of genomic and
      proteomic expression of human early placental villous trophoblast cells followed
      by a commentary on the future directions of research in this field. 

PMID- 24291664
TI  - Stabilisation/solidification of APC residues from MSW incineration with hydraulic
      binders and chemical additives.
AB  - This study focuses on the stabilisation/solidification (S/S) treatment of air
      pollution control (APC) residues from municipal solid waste (MSW) incineration.
      Six formulations (T1-T6) were tested based on different cements as binders, for
      the immobilisation of pollutants and to prevent their entering into the
      environment at unacceptable rates. Soluble phosphates and silicates were
      considered in some cases to fix heavy metals. The performance of T1-T6 products
      was measured in terms of initial and final setting times, mechanical strength,
      total availability and leaching from S/S products. Two monolithic leaching tests
      were used to estimate emissions of pollutants over 48h and 64 days. The results
      showed that the setting time was reduced when soluble phosphates were used.
      Moreover, although all the treatments have met the threshold of 1MPa for
      unconfined compressive strength, this parameter was significantly reduced due to
      matrix dissolution during immersion. After three cycles of leaching, the limit of
      10% for solubilisation was exceeded for all treatments with the exception of T5
      (with phosphates). This study demonstrated that the S/S treatment used at the
      industrial level can be improved with respect to toxic heavy metals, by using
      soluble silicates or phosphates, but not regarding soluble salts. 

PMID- 24291665
TI  - Characterization of the interactions between protein and carbon black.
AB  - A considerable amount of studies have been conducted to investigate the
      interactions of biological fluids with nanoparticle surfaces, which exhibit a
      high affinity for proteins and particles. However, the mechanisms underlying
      these interactions have not been elucidated, particularly as they relate to human
      health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid
      (BALF) as models for protein-particle conjugates, we characterized the
      physicochemical modifications of carbon blacks (CB) with 23nm or 65nm in diameter
      after protein treatment. Adsorbed BALF-containing proteins were quantified and
      identified by pathways, biological analyses and protein classification.
      Significant modifications of the physicochemistry of CB were induced by the
      addition of BSA. Enzyme modulators and hydrolase predominately interacted with
      CB, with protein-to-CB interactions that were associated with the coagulation
      pathways. Additionally, our results revealed that an acute-phase response could
      be activated by these proteins. With regard to human health, the present study
      revealed that the CB can react with proteins (~55kDa and 70kDa) after inhalation
      and may modify the functional structures of lung proteins, leading to the
      activation of acute-inflammatory responses in the lungs. 

PMID- 24291666
TI  - Nitrile-functionalized tertiary amines as highly efficient and reversible SO2
      absorbents.
AB  - Three different types of nitrile-functionalized amines, including 3-(N,N
      diethylamino)propionitrile (DEAPN), 3-(N,N-dibutylamino)propionitrile (DBAPN),
      and N-methyl-N,N-dipropionitrile amine (MADPN) were synthesized, and their SO2
      absorption performances were evaluated and compared with those of hydroxy
      functionalized amines such as N,N-diethyl-N-ethanol amine (DEEA), N,N-dibutyl-N
      ethanol amine (DBEA), and N-methyl-N,N-diethanol amine (MDEA). Absorption
      desorption cycle experiments clearly demonstrate that the nitrile-functionalized
      amines are more efficient than the hydroxy-functionalized amines in terms of
      absorption rate and regenerability. Computational calculations with DBEA and
      DBAPN revealed that DBEA bearing a hydroxyethyl group chemically interacts with
      SO2 through oxygen atom, forming an ionic compound with a covalently bound OSO2(
      ) group. On the contrary, DBAPN bearing a nitrile group physically interacts with
      SO2 through the nitrogen and the hydrogen atoms of the two methylene groups
      adjacent to the amino and nitrile functionalities. 

PMID- 24291667
TI  - Direct observation of cesium at the interlayer region in phlogopite mica.
AB  - To investigate the sorption mechanism of cesium (Cs) into clay minerals, high
      resolution (scanning) transmission electron microscopy (TEM/STEM) imaging of Cs
      in mica (phlogopite) has been conducted. Platy phlogopite powders were immersed
      in a cesium chloride (CsCl) solution to achieve Cs(+)-K(+) ion-exchange at the
      interlayer regions in phlogopite. To observe many phlogopite particles with the
      incident electron beam parallel to the mica layers, cross-sectional thin
      specimens were prepared from sedimented particles using a focused ion beam. High
      angle annular dark-field imaging with STEM is superior to conventional high
      resolution TEM (HRTEM) for visualizing Cs at interlayer sites even in thicker
      crystal regions and/or at lower magnification due to the intense Z-contrast of
      Cs. However, HRTEM is also practical for estimating the concentration of Cs at
      the interlayer site from the thickness dependence of the contrast at the
      interlayer region. Cs sorption of micas was previously thought to be localized
      mainly at the frayed-edge sites of mica crystals. However, the present
      observations indicate that Cs substitution of K occurs not around crystal edges
      but deep inside the crystals along specific interlayer regions. 

PMID- 24291668
TI  - Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine
      enkephalin (MENK).
AB  - The aim of this study was to investigate the immunological mechanisms by which
      synthetic methionine enkephalin (MENK) exerts therapeutic effects on tumor
      growth. Our findings in vivo or in vitro show that MENK treatment either in vivo
      or in vitro could up-regulate the percentages of CD8+T cells, induce markers of
      activated T cells, increased cytotoxic activity against mouse S180 tumor cells
      and increase secretion of IFNgamma. In addition, the adoptively transferred CD8+T
      cells, after either in vitro or in vivo treatment with MENK, result in
      significantly increased survival of S180 tumor-bearing mice and significant
      shrinkage in tumor growth. Opioid receptors are detected on normal CD8+T cells
      and exposure to MENK leads to increased expression of opioid receptors.
      Interaction between MENK and the opioid receptors on CD8+T cells appears to be
      essential for the activation of CTL, since the addition of naltrexone (NTX), an
      opioid receptor antagonist, significantly inhibits all of the effects of MENK.
      The evidence obtained indicates that the MENK-induced T cell signaling is
      associated with a significant up-regulation of Ca2+ influx into the cytoplasm and
      the translocation of NFAT2 into nucleus, and these signaling effects are also
      inhibited by naltrexone.

PMID- 24291669
TI  - Sports and brain morphology - a voxel-based morphometry study with endurance
      athletes and martial artists.
AB  - Physical exercises and motor skill learning have been shown to induce changes in
      regional brain morphology, this has been demonstrated for various activities and
      tasks. Also individuals with special skills show differences in regional brain
      morphology. This has been indicated for professional musicians, London taxi
      drivers, as well as for athletes like dancers, golfers and judokas. However
      little is known about whether sports with different metabolic profiles (aerobic
      vs. anaerobic) are associated with different patterns of altered brain
      morphology. In this cross-sectional study we investigated two groups of high
      performance athletes, one group performing sports that are thought to be mainly
      aerobic, and one group performing sports known to have intermittent phases of
      anaerobic metabolism. Using high-resolution structural imaging and voxel-based
      morphometry (VBM), we investigated a group of 26 male athletes consisting of 13
      martial artists and 13 endurance athletes as well as a group of non-exercising
      men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the
      supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as
      compared to the control group. In addition, endurance athletes showed
      significantly higher GM volume in the medial temporal lobe (MTL), specifically in
      the hippocampus and parahippocampal gyrus, which was not seen in the martial arts
      group. Our data suggest that high-performance sports are associated with changes
      in regional brain morphology in areas implicated in motor planning and motor
      learning. In addition high-level endurance sports seem to affect MTL structures,
      areas that have previously been shown to be modulated by aerobic exercise. 

PMID- 24291670
TI  - Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects
      the expressions of pCREB and c-Fos in the insular cortex.
AB  - Stress affects brain activity and promotes long-term changes in multiple neural
      systems. Exposure to stressors causes substantial effects on the perception and
      response to pain. In several animal models, chronic stress produces lasting
      hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the
      regions exhibiting most reliable pain-related activity. And the IC and ACC play
      an important role in pain modulation via the descending pain modulatory system.
      In the present study we examined the expression of phospho-cAMP response element
      binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS)
      and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral
      cortices that affect the activity of the descending pain modulatory system in the
      rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced
      an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA
      injection into the hindpaw after the FS shows significantly enhanced thermal
      hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the
      posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos
      immunoreactive neurons in the left AIC and PIC were significantly lower in the
      FS+CFA group (L AIC, 95.9+/-6.8; L PIC, 181.9+/-23.1) than those in the naive
      group (L AIC, 151.1+/-19.3, p<0.05; L PIC, 274.2+/-37.3, p<0.05). These findings
      suggest a neuroplastic change in the IC after FS, which may be involved in the
      enhancement of CFA-induced thermal hyperalgesia through dysfunction of the
      descending pain modulatory system. 

PMID- 24291672
TI  - Synchrotron X-ray micro-computed tomography as a tool for in situ elucidation of
      insect bacteriomes.
AB  - Obligate bacterial endosymbionts are common, influential associates of
      arthropods, and are often found in specific organs termed bacteriomes. Three
      dimensional images of bacteriomes of the leafhopper Orosius albicinctus
      (Hemiptera: Cicadellidae) were reconstructed from synchrotron-based X-ray micro
      computed tomography (CT). Results show that bilateral bacteriomes are located
      between the first and second abdominal tergites, are mushroom-shaped and consist
      two different types of tissue. Fluorescence in situ hybridization reveals that
      the primary bacterial symbiont Sulcia muelleri is in the 'cap' part of the of
      organ. The technique allows a noninvasive, in situ, means of visualizing
      bacteriomes and will facilitate understanding their form and function. 

PMID- 24291673
TI  - Unique rostrate larvae and basidiomycophagy in the beetle family Corylophidae.
AB  - The head morphology of larvae of two undescribed species of the corylophid genus
      Holopsis were examined. Both are associated with the same basidiomycete host
      Ganoderma cf applanatum. Whereas the round and convex adults are very similar,
      one of the disc-shaped larvae is characterized by an elongate weevil-like snout,
      which is a unique feature in larval beetles. The posterior head region, the
      mouthparts and the general configuration of the musculature are similar in the
      larvae of both species. However, in the rostrate Holopsis sp. 1 most muscles are
      either widened along the longitudinal axis or elongated. Moreover, an additional
      bundle of M. frontobuccalis posterior is present, which strengthens the
      pharyngeal pumping apparatus. Both species share an unusual connection between
      the prepharynx and pharynx. This is a potential autapomorphy of the genus. The
      larval cephalic morphology of Holopsis sp. 2 and the corylophine genus
      Sericoderus is quite similar. However, they differ in some muscular features and
      in the configuration of the foregut. Holopsis species are associated with
      Basidiomycetes. Whether this is an ancestral condition in Corylophidae remains
      ambiguous due to conflicting phylogenetic hypotheses and the largely unknown
      biology of the Australian subfamily Periptyctinae. Several features of Holopsis
      are likely plesiomorphic and possibly related with the association with
      basidiomycetes. However, the larval rostrum of sp. 1 is doubtlessly derived, and
      could have a performance advantage over other species feeding on the spores of
      Ganoderma cf applanatum including Holopsis sp. 2. 

PMID- 24291671
TI  - Novel Vitamin K analogs suppress seizures in zebrafish and mouse models of
      epilepsy.
AB  - Epilepsy is a debilitating disease affecting 1-2% of the world's population.
      Despite this high prevalence, 30% of patients suffering from epilepsy are not
      successfully managed by current medication suggesting a critical need for new
      anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the
      management of epilepsy, we began our study by screening drugs that, like some
      currently used AEDs, inhibit histone deacetylases (HDACs) using a well
      established larval zebrafish model. In this model, 7-day post fertilization (dpf)
      larvae are treated with the widely used seizure-inducing compound
      pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior
      previously determined to be a measurable manifestation of seizures. In our first
      screen, we tested a number of different HDAC inhibitors and found that one, 2
      benzamido-1 4-naphthoquinone (NQN1), significantly decreased swim activity to
      levels equal to that of valproic acid, 2-n-propylpentanoic acid (VPA). We
      continued to screen structurally related compounds including Vitamin K3 (VK3) and
      a number of novel Vitamin K (VK) analogs. We found that VK3 was a robust
      inhibitor of the PTZ-induced swim activity, as were several of our novel
      compounds. Three of these compounds were subsequently tested on mouse seizure
      models at the National Institute of Neurological Disorders and Stroke (NINDS)
      Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well
      in the minimal clonic seizure (6Hz) and corneal-kindled mouse models of epilepsy,
      with no observable toxicity. As VK3 affects mitochondrial function, we tested the
      effects of our compounds on mitochondrial respiration and ATP production in a
      mouse hippocampal cell line. We demonstrate that these compounds affect ATP
      metabolism and increase total cellular ATP. Our data indicate the potential
      utility of these and other VK analogs for the prevention of seizures and suggest
      the potential mechanism for this protection may lie in the ability of these
      compounds to affect energy production. 

PMID- 24291674
TI  - Methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL), a synthetic oleanolic
      acid derivative, induces both apoptosis and autophagy in MDA-MB-231 breast cancer
      cells.
AB  - HIMOXOL (methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate) is a synthetic
      derivative of oleanolic acid (OA). HIMOXOL revealed the highest cytotoxic effect
      among tested synthetic OA analogs. In this study we focused on elucidating the
      cytotoxic mechanism of HIMOXOL in MDA-MB-231 breast cancer cells. HIMOXOL reduced
      MDA-MB-231 cell viability with an IC50 value of 21.08+/-0.24MUM. In contrast to
      OA, the tested compound induced cell death by activating apoptosis and the
      autophagy pathways. More specifically, we found that HIMOXOL was able to activate
      the extrinsic apoptotic pathway, which was proven by observation of caspase-8,
      caspase-3 and PARP-1 protein activation in Western blot analysis. An increase in
      the ratio of Bax/Bcl-2 protein levels was also detected. Moreover, HIMOXOL
      triggered microtubule-associated protein LC3-II expression and upregulated beclin
      1. This observed compound activity was modulated by mitogen-activated protein
      kinases and NFkappaB/p53 signaling pathways. Together, these data suggest that
      HIMOXOL, a synthetic oleanolic acid derivative which activates dual cell death
      machineries, could be a potential and novel chemotherapeutic agent. 

PMID- 24291675
TI  - Neutralization of interleukin-17A delays progression of silica-induced lung
      inflammation and fibrosis in C57BL/6 mice.
AB  - Silica exposure can cause lung inflammation and fibrosis, known as silicosis.
      Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling
      inflammatory diseases. However, the roles of IL-17A and Th17 cells in the
      progress of silica-induced inflammation and fibrosis are poorly understood. This
      study explored the effects of IL-17A on silica-induced inflammation and fibrosis.
      We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice
      model, and mice were exposed to silica to establish an experimental silicosis
      model. We showed that IL-17A neutralization delayed neutrophil accumulation and
      progression of silica-induced lung inflammation and fibrosis. IL-17A
      neutralization reduced the percentage of Th17 in CD4+ T cells, decreased IL-6 and
      IL-1beta expression, and increased Tregs at an early phase of silica-induced
      inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and
      autoimmune responses. These results suggest that IL-17A neutralization alleviates
      early stage silica-induced lung inflammation and delays progression of silica
      induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17
      cell development by decreasing IL-6 and/or IL-1beta and increased Tregs at an
      early phase of silica-induced inflammation. Neutralization of IL-17A also delayed
      the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis.
      IL-17A may play a pivotal role in the early phase of silica-induced inflammation
      and may mediate the Th immune response to influence silica-induced lung
      inflammation and fibrosis in mice. 

PMID- 24291676
TI  - Bio-inspired photoresponse of porphyrin-attached gold nanoparticles on a field
      effect transistor.
AB  - A bio-inspired photoresponse was engineered in porphyrin-attached Au
      nanoparticles (AuNPs) on a field-effect transistor (FET). The system mimics
      photosynthetic electron transfer, using porphyrin derivatives as photosensitizers
      and AuNPs as photoelectron counting devices. Porphyrin-protected AuNPs were
      immobilized onto the gate of an FET via the formation of self-assembled
      monolayers. Photoinduced electron transfer from the porphyrin led to single
      electron transfer at the Au nanoparticles, which was monitored via a changing
      gate voltage on the FET in the presence of organic electrolyte. The further
      attachment of other functional molecules to this system should enable various
      other potential functionalities. This article is part of a special issue
      entitled: photosynthesis research for sustainability: keys to produce clean
      energy.

PMID- 24291677
TI  - Ecological study of hantavirus infection in wild rodents in an endemic area in
      Brazil.
AB  - A 3-year ecological study of small mammals was carried out in an endemic area for
      hantavirus pulmonary syndrome in the state of Santa Catarina in Southern Brazil.
      A total of 994 rodents of 14 different species corresponding to the subfamilies
      of Sigmodontinae, Murinae, Eumysopinae, and Caviinae were captured during 2004
      2006. Oligoryzomys nigripes and Akodon montensis were the most abundant species
      and showed a clear seasonal pattern with higher population sizes during the
      winter. Rodent population outbreaks, associated within bamboo mast seeding
      events, were detected predominantly in areas where hantavirus pulmonary syndrome
      cases were notified in the state. Antibody reactivity to Hantavirus was detected
      in five sigmodontine species: O. nigripes (39/435), A. montensis (15/318), Akodon
      paranaensis (4/37), Thaptomys nigrita (1/86) and Sooretamys angouya (1/12). The
      highest hantavirus antibody prevalence occurred during the period of highest
      population size in A. montensis. For O. nigripes, hantavirus prevalence was
      higher in late spring, when reproduction was more frequent. Co-circulation of
      Juquitiba (JUQV) and Jabora (JABV) viruses was observed - JABV in A. paranaensis
      and A. montensis; JUQV in O. nigripes and T. nigrita. JABV occurrence was
      associated to gender and population size of the rodent while JUQV was related to
      gender, season, temperature, and locality. 

PMID- 24291678
TI  - Gastric bypass with unknown intestinal malrotation: Required attitude.
AB  - INTRODUCTION: Intestinal malrotations are rare and may be asymptomatic until
      adulthood. There are only a few descriptions of gastric bypass with intestinal
      malrotation. If the duodenojejunal angle is not correctly seen, as is generally
      the case, there is a risk of creating an antiperistaltic anastomosis.
      PRESENTATION OF CASE: We describe required attitude and cases of gastric bypass
      performed on two patients who had a complete common mesentery. In both of our
      patients, the transverse colon was not running across the abdomen and the
      duodenojejunal angle was "absent". We therefore looked for the caecum in order to
      unravel all of the small intestine. We were able to carry out Roux en Y gas- 42
      tric bypass with uncomplicated post-operative courses for both 43 patients. The
      result in weight loss was perfect and identical to that of patients without
      anatomical abnormality. DISCUSSION: In our cases, ultrasound to investigate for
      gallstones did not provide a pre-operative diagnosis. It is extremely difficult
      to investigate for the mesenteric vessels by ultrasound in obese patients and for
      this reason the finding was not made preoperatively. The most important thing to
      do is make the diagnosis of malrotation preoperatively. For this reason the
      golden rule in performing a gastric bypass is to clearly visualise the
      duodenojejunal angle which allows an unknown bowel malrotation to be identified.
      Following these cases, the study of the oeso-gastro-jejeunal transit is now part
      of our pre-operative assessment. CONCLUSION: Bariatric surgeons need to be aware
      of these abnormalities. If a common mesentery is present the gastric bypass can
      still be performed.

PMID- 24291679
TI  - Primary umbilical endometriosis. Case report and discussion on management
      options.
AB  - INTRODUCTION: We report a recently observed case of primary umbilical
      endometriosis (UE), with the main aim to discuss the management of this rare
      condition. PRESENTATION OF CASE: A 24-year-old woman complained of a painful
      nodule on her umbilical region, bleeding with her menstrual cycle.
      Ultrasonography showed a hypoechoic superficial mass in the umbilicus and no
      signs of intra-abdominal endometriosis. Excision of the nodule under local
      anesthesia was performed. Histopathological analysis confirmed the diagnosis of
      umbilical endometriosis. Neither symptoms nor signs of local recurrence have been
      observed after 24 months. DISCUSSION: UE should be taken into account in
      differential diagnosis of umbilical disorders even in young nulliparous women
      with no typical symptoms of pelvic endometriosis. Although there is a substantial
      agreement about the necessity of surgery, treatment options are either local
      excision of the lesion or removal of the whole umbilicus with or without
      laparoscopic exploration of the peritoneal cavity. The decision should be
      tailored for the individual patient, taking into consideration the size of the
      lesion, the duration of symptoms and the presence of possible pelvic
      endometriosis. CONCLUSION: Local excision saving the umbilicus may be the
      treatment of choice in patients with small UE lesions.

PMID- 24291680
TI  - Craniofacial trauma and double epidural hematomas from horse training.
AB  - INTRODUCTION: A case of complex poly-trauma requiring multi-service management of
      rare, diagnoses is reviewed. PRESENTATION OF CASE: A healthy 20 year old female
      suffered double epidural hematoma, base of, skull fracture, traumatic cranial
      nerve X palsy, benign positional paroxysmal vertigo and supraorbital, neuralgia
      following equestrian injury. DISCUSSION: Epidemiology, differential diagnosis,
      and principles of management for each condition, are reviewed. CONCLUSION:
      Coordinated trauma care is well suited to address the complex poly trauma
      following, equestrian injury.

PMID- 24291681
TI  - Internal transomental herniation with a trapped small bowel mimicking acute
      appendicitis.
AB  - INTRODUCTION: Internal herniation with subsequent bowel obstruction is uncommon,
      and making a correct diagnosis prior to surgery is often difficult. PRESENTATION
      OF CASE: In this case report we present a man, who suffered from sudden extreme
      right-sided abdominal pain. The diagnostic workup was inconclusive. Emergency
      surgery was indicated with a suspicion of acute appendicitis. We found a
      strangulated ileus caused by an internal herniation of the small intestine
      through a hole in the greater omentum. The patient had no history of surgery or
      other physical disorders explaining this finding. The obstruction was resolved
      and the postoperative clinical course was uncomplicated. DISCUSSION: A thorough
      diagnostic workup including CT scan would most probably have given the correct
      diagnosis. However, the clinical course and initiation of the correct treatment
      would have been delayed significantly. CONCLUSION: We suggest that the diagnostic
      workup of patients with unclear lower abdominal pain should be limited and that
      acute clinical symptoms require rapid laparoscopic evaluation and surgical
      treatment.

PMID- 24291682
TI  - Cardiac metastasis from gallbladder carcinoma.
AB  - INTRODUCTION: Primary gallbladder carcinoma is a rare aggressive neoplasm of
      elderly with poor prognosis. The tumour is often unresectable at the time of
      diagnosis. Metastasis to heart is rare and only 6 cases have been reported in the
      indexed literature. We herein report a case of gallbladder carcinoma
      metastasizing to heart. PRESENTATION OF CASE: A 54 year old female presented with
      dyspnoea and chest pain with past history of radical cholecystectomy and
      palliative chemotherapy for adenocarcinoma of gallbladder. Chest X-ray showed
      cardiomegaly and 2-D ECHO revealed features of tumour deposits on the surface of
      myocardium and malignant pericardial effusion. Mini-thoracotomy and pericardial
      window procedure was done to relieve distressing symptoms and biopsy of
      pericardial tissue revealed metastatic adenocarcinoma. In spite of intensive
      care, patient succumbed to disease in the post-operative period. DISCUSSION:
      Primary adenocarcinoma of gallbladder is the most common malignancy of biliary
      tract and fifth most common malignancy of gastro-intestinal system with dismal
      prognosis. It most commonly spreads to liver and regional lymph nodes, very
      rarely distant metastasis occurs to kidney, adrenal, thyroid and bones as
      reported in the literature. Metastasis to heart presents with symptoms of cardiac
      failure due to pericardial effusion. Even with intensive care patients will
      invariably succumb to the disease. CONCLUSION: Metastatic spread to heart from
      carcinoma of gallbladder is very rare. Should a patient be suspected of or an
      operated case of gallbladder carcinoma present with symptoms of congestive heart
      failure and massive pericardial effusion, cardiac metastasis should be
      considered.

PMID- 24291683
TI  - Striking volume intolerance is induced by mimicking arterial baroreflex failure
      in normal left ventricular function.
AB  - BACKGROUND: Patients with heart failure and preserved ejection fraction (HFpEF)
      are supersensitive to volume overload, and a striking increase in left atrial
      pressure (LAP) often occurs transiently and is rapidly resolved by intravascular
      volume reduction. The arterial baroreflex is a powerful regulator of
      intravascular stressed blood volume. We examined whether arterial baroreflex
      failure (FAIL) mimicked by constant carotid sinus pressure (CSP) causes a
      striking increase in LAP and systemic arterial pressure (AP) by volume loading in
      rats with normal left ventricular (LV) function. METHODS AND RESULTS: In
      anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses and
      controlled CSP by a servo-controlled piston pump. We mimicked the normal arterial
      baroreflex by matching CSP to instantaneous AP and FAIL by maintaining CSP at a
      constant value regardless of AP. We infused dextran stepwise (infused volume
      [Vi]) until LAP reached 15 mm Hg and obtained the LAP-Vi relationship. We
      estimated the critical Vi as the Vi at which LAP reached 20 mm Hg. In FAIL,
      critical Vi decreased markedly from 19.4 +/- 1.6 mL/kg to 15.6 +/- 1.6 mL/kg (P <
      .01), whereas AP at the critical Vi increased (194 +/- 6 mm Hg vs 163 +/- 6 mm
      Hg; P < .01). We demonstrated that an artificial arterial baroreflex system we
      recently developed could fully restore the physiologic volume intolerance in the
      absence of native arterial baroreflex. CONCLUSIONS: Arterial baroreflex failure
      induces striking volume intolerance in the absence of LV dysfunction and may play
      an important role in the pathogenesis of acute heart failure, especially in
      states of HFpEF.

PMID- 24291684
TI  - Relationships between changes in time spent walking since middle age and incident
      functional disability.
AB  - OBJECTIVE: To examine the relationship between changes in time spent walking
      since middle age and incident functional disability. METHOD: In 2006, we
      conducted a prospective cohort study of 7177 disability-free Japanese individuals
      aged >=65years who lived in Ohsaki City, Miyagi Prefecture, Japan. Participants
      were categorized into four groups according to changes in time spent walking
      based on two questionnaire surveys conducted in 1994 and in 2006. Incident
      functional disability was retrieved from the public Long-term Care Insurance
      database, and the subjects were followed up for 5years. The Cox proportional
      hazards model was used to investigate the association between changes in time
      spent walking and the risk of incident functional disability. RESULTS: Compared
      with subjects who remained sedentary, the multivariate-adjusted hazard ratios
      (95% confidence intervals) were 0.69 (0.49-0.98) among those who became active
      and 0.64 (0.50-0.82) among those who remained active. These results did not alter
      when analyses were stratified by gender, age and motor function status.
      CONCLUSION: An increase in time spent walking among sedentary adults is
      significantly associated with a lower risk of incident functional disability.

PMID- 24291685
TI  - Maternal depression and childhood obesity: a systematic review.
AB  - OBJECTIVE: Maternal depression is prevalent and has been associated with
      parenting practices that influence child weight. In this systematic review we
      aimed to examine the prospective association between maternal depression and
      child overweight. METHODS: We searched four databases (PsycINFO, PubMed, Embase,
      and Academic Search Premier) to identify studies for inclusion. We included
      studies with a prospective design with at least one year follow-up, measuring
      maternal depression at any stage after childbirth, and examining child overweight
      or obesity status, body mass index z-score or percentile, or adiposity. Two
      authors extracted data independently and findings were qualitatively synthesized.
      RESULTS: We identified nine prospective studies for inclusion. Results were
      examined separately for episodic depression (depression at a single measurement
      occasion) and chronic depression (depression on multiple measurement occasions).
      Mixed results were observed for the relationship between episodic depression and
      indicators of child adiposity. Chronic depression, but not episodic depression,
      was associated with greater risk for child overweight. CONCLUSIONS: While chronic
      depression may be associated with child overweight, further research is needed.
      Research is also needed to determine whether maternal depression influences child
      weight outcomes in adolescence and to investigate elements of the family ecology
      that may moderate the effect of maternal depression on child overweight.

PMID- 24291686
TI  - Skeletal muscle mitochondria: a major player in exercise, health and disease.
AB  - BACKGROUND: Maintaining skeletal muscle mitochondrial content and function is
      important for sustained health throughout the lifespan. Exercise stimulates
      important key stress signals that control skeletal mitochondrial biogenesis and
      function. Perturbations in mitochondrial content and function can directly or
      indirectly impact skeletal muscle function and consequently whole-body health and
      wellbeing. SCOPE OF REVIEW: This review will describe the exercise-stimulated
      stress signals and molecular mechanisms positively regulating mitochondrial
      biogenesis and function. It will then discuss the major myopathies, neuromuscular
      diseases and conditions such as diabetes and ageing that have dysregulated
      mitochondrial function. Finally, the impact of exercise and potential
      pharmacological approaches to improve mitochondrial function in diseased
      populations will be discussed. MAJOR CONCLUSIONS: Exercise activates key stress
      signals that positively impact major transcriptional pathways that transcribe
      genes involved in skeletal muscle mitochondrial biogenesis, fusion and
      metabolism. The positive impact of exercise is not limited to younger healthy
      adults but also benefits skeletal muscle from diseased populations and the
      elderly. Impaired mitochondrial function can directly influence skeletal muscle
      atrophy and contribute to the risk or severity of disease conditions.
      Pharmacological manipulation of exercise-induced pathways that increase skeletal
      muscle mitochondrial biogenesis and function in critically ill patients, where
      exercise may not be possible, may assist in the treatment of chronic disease.
      GENERAL SIGNIFICANCE: This review highlights our understanding of how exercise
      positively impacts skeletal muscle mitochondrial biogenesis and function.
      Exercise not only improves skeletal muscle mitochondrial health but also enables
      us to identify molecular mechanisms that may be attractive targets for
      therapeutic manipulation. This article is part of a Special Issue entitled
      Frontiers of mitochondrial research.

PMID- 24291687
TI  - Der p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic
      allergens produced by the house dust mite Dermatophagoides pteronyssinus.
AB  - BACKGROUND: The enzymatic activity of the four proteases found in the house dust
      mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy.
      Our aim was to elucidate the activation cascade of their corresponding precursor
      forms and particularly to highlight the interconnection between proteases during
      this cascade. METHODS: The cleavage of the four peptides corresponding to the
      mite zymogen activation sites was studied on the basis of the Forster Resonance
      Energy Transfer method. The proDer p 6 zymogen was then produced in Pichia
      pastoris to elucidate its activation mechanism by mite proteases, especially Der
      p 1. The role of the propeptide in the inhibition of the enzymatic activity of
      Der p 6 was also examined. Finally, the Der p 1 and Der p 6 proteases were
      localised via immunolocalisation in D. pteronyssinus. RESULTS: All peptides were
      specifically cleaved by Der p 1, such as proDer p 6. The propeptide of proDer p 6
      inhibited the proteolytic activity of Der p 6, but once cleaved, it was degraded
      by the protease. The Der p 1 and Der p 6 proteases were both localised to the
      midgut of the mite. CONCLUSIONS: Der p 1 in either its recombinant form or in the
      natural context of house dust mite extracts specifically cleaves all zymogens,
      thus establishing its role as a major activator of both mite cysteine and serine
      proteases. GENERAL SIGNIFICANCE: This finding suggests that Der p 1 may be
      valuable target against mites.

PMID- 24291689
TI  - DNA damage dependent activation of checkpoint kinase-1 and mitogen-activated
      protein kinase-p38 are required in malabaricone C-induced mitochondrial cell
      death.
AB  - BACKGROUND: Given that lung cancer is the second leading cause of cancer-related
      deaths with low survival rates, the project was aimed to formulate an efficient
      drug with minimum side effects, and rationalize its action mechanistically.
      METHODS: Mitochondria deficient cells, shRNA-mediated BCL2 and ATM depleted cells
      and pharmacological inhibition of DNA-damage response proteins were employed to
      explore the signaling mechanism governed between nucleus and mitochondria in
      response to mal C. RESULTS: Mal C decreased cell viability in three lung
      carcinoma cells, associated with DNA damage, p38-MAPK activation, imbalance in
      BAX/BCL2 expression, mitochondrial dysfunction and cytochrome-c release.
      Mitochondria depletion and p38-MAPK inhibition made A549 cells extremely
      resistant, but BCL2 knock-down partially sensitized the cells to mal C treatment.
      The mal C-induced apoptosis in A549 cells was initiated by DNA single strand
      breaks that led to double strand breaks (DSBs). DSB generation paralleled the
      induction of ATM- and ATR-mediated CHK1 phosphorylation. ATM silencing and ATR
      inhibition partially attenuated the mal C-induced p38-MAPK activation, CHK1
      phosphorylation and apoptosis, which were completely suppressed by CHK1
      inhibition. CONCLUSIONS: Mal C activates the ATM-CHK1-p38 MAPK cascade to cause
      mitochondrial cell death in lung carcinoma cells. GENERAL SIGNIFICANCE: Given
      that mal C has appreciable natural abundance and is non-toxic to mice, further in
      vivo evaluation would help in establishing its anti-cancer property.

PMID- 24291688
TI  - Aquaglyceroporins: generalized metalloid channels.
AB  - BACKGROUND: Aquaporins (AQPs), members of a superfamily of transmembrane channel
      proteins, are ubiquitous in all domains of life. They fall into a number of
      branches that can be functionally categorized into two major sub-groups: i)
      orthodox aquaporins, which are water-specific channels, and ii)
      aquaglyceroporins, which allow the transport of water, non-polar solutes, such as
      urea or glycerol, the reactive oxygen species hydrogen peroxide, and gases such
      as ammonia, carbon dioxide and nitric oxide and, as described in this review,
      metalloids. SCOPE OF REVIEW: This review summarizes the key findings that AQP
      channels conduct bidirectional movement of metalloids into and out of cells.
      MAJOR CONCLUSIONS: As(OH)3 and Sb(OH)3 behave as inorganic molecular mimics of
      glycerol, a property that allows their passage through AQP channels. Plant AQPs
      also allow the passage of boron and silicon as their hydroxyacids, boric acid
      (B(OH)3) and orthosilicic acid (Si(OH)4), respectively. Genetic analysis suggests
      that germanic acid (GeO2) is also a substrate. While As(III), Sb(III) and Ge(IV)
      are toxic metalloids, borate (B(III)) and silicate (Si(IV)) are essential
      elements in higher plants. GENERAL SIGNIFICANCE: The uptake of environmental
      metalloids by aquaporins provides an understanding of (i) how toxic elements such
      as arsenic enter the food chain; (ii) the delivery of arsenic and antimony
      containing drugs in the treatment of certain forms of leukemia and chemotherapy
      of diseases caused by pathogenic protozoa; and (iii) the possibility that food
      plants such as rice could be made safer by genetically modifying them to exclude
      arsenic while still accumulating boron and silicon. This article is part of a
      Special Issue entitled Aquaporins.

PMID- 24291690
TI  - Atomic Force Microscopy and pharmacology: from microbiology to cancerology.
AB  - BACKGROUND: Atomic Force Microscopy (AFM) has been extensively used to study
      biological samples. Researchers take advantage of its ability to image living
      samples to increase our fundamental knowledge (biophysical properties/biochemical
      behavior) on living cell surface properties, at the nano-scale. SCOPE OF REVIEW:
      AFM, in the imaging modes, can probe cells morphological modifications induced by
      drugs. In the force spectroscopy mode, it is possible to follow the
      nanomechanical properties of a cell and to probe the mechanical modifications
      induced by drugs. AFM can be used to map single molecule distribution at the cell
      surface. We will focus on a collection of results aiming at evaluating the nano
      scale effects of drugs, by AFM. Studies on yeast, bacteria and mammal cells will
      illustrate our discussion. Especially, we will show how AFM can help in getting a
      better understanding of drug mechanism of action. MAJOR CONCLUSIONS: This review
      demonstrates that AFM is a versatile tool, useful in pharmacology. In
      microbiology, it has been used to study the drugs fighting Candida albicans or
      Pseudomonas aeruginosa. The major conclusions are a better understanding of the
      microbes' cell wall and of the drugs mechanism of action. In cancerology, AFM has
      been used to explore the effects of cytotoxic drugs or as an innovative
      diagnostic technology. AFM has provided original results on cultured cells, cells
      extracted from patient and directly on patient biopsies. GENERAL SIGNIFICANCE:
      This review enhances the interest of AFM technologies for pharmacology. The
      applications reviewed range from microbiology to cancerology.

PMID- 24291691
TI  - Fibrin(ogen)olytic enzymes in scorpion (Tityus discrepans) venom.
AB  - Several fibrin(ogen)olytic enzymes from Tityus discrepans (Buthidae, Buthoidea)
      venom (TdV) were partially purified on a Sephadex G-50 column, by affinity and
      molecular exclusion high-performance chromatography. Fractions SB1-I and SB1-II
      had fibrinolytic, fibrinogenolytic (Aalpha-chains degradation) and tissue
      plasminogen activator (t-PA)-like activities. SB1-III was only fibrinogenolytic
      (fast degradation of Aalpha-chains and slower degradation of fibrinogen Bbeta
      chains). These results showed the presence of alpha-fibrinogenases in TdV. The
      fibrino(geno)lytic activity in these fractions was abolished by metalloprotease
      inhibitors (MPI). Fractions SB3-I and SB3-II contain fibrinogenolytic (Aalpha
      chains degradation) and fibronectinolytic activities. Also fraction SB3-I had a t
      PA-like activity. Activities in SB3-I and SB3-II were abolished by serine
      protease inhibitors (SPI). None of the fractions degraded fibrinogen gamma
      chains. Fibrinogen degradation by active fractions is associated with an
      anticoagulant effect supported by a reduced coagulant activity. The overall
      outcome suggests that metalloproteases and serine proteases in TdV are
      responsible for fibrin(ogen)olytic activity because MPI and SPI inhibited these
      activities. 

PMID- 24291692
TI  - Hyperdense middle cerebral artery sign.

PMID- 24291693
TI  - Batch gradient method with smoothing L1/2 regularization for training of
      feedforward neural networks.
AB  - The aim of this paper is to develop a novel method to prune feedforward neural
      networks by introducing an L1/2 regularization term into the error function. This
      procedure forces weights to become smaller during the training and can eventually
      removed after the training. The usual L1/2 regularization term involves absolute
      values and is not differentiable at the origin, which typically causes
      oscillation of the gradient of the error function during the training. A key
      point of this paper is to modify the usual L1/2 regularization term by smoothing
      it at the origin. This approach offers the following three advantages: First, it
      removes the oscillation of the gradient value. Secondly, it gives better pruning,
      namely the final weights to be removed are smaller than those produced through
      the usual L1/2 regularization. Thirdly, it makes it possible to prove the
      convergence of the training. Supporting numerical examples are also provided. 

PMID- 24291694
TI  - A case for caution in the pursuit of the sentinel node in women with endometrial
      carcinoma.

PMID- 24291695
TI  - An automated method of quantifying ferrite microstructures using electron
      backscatter diffraction (EBSD) data.
AB  - The identification and quantification of the different ferrite microconstituents
      in steels has long been a major challenge for metallurgists. Manual point
      counting from images obtained by optical and scanning electron microscopy (SEM)
      is commonly used for this purpose. While classification systems exist, the
      complexity of steel microstructures means that identifying and quantifying these
      phases is still a great challenge. Moreover, point counting is extremely tedious,
      time consuming, and subject to operator bias. This paper presents a new automated
      identification and quantification technique for the characterisation of complex
      ferrite microstructures by electron backscatter diffraction (EBSD). This
      technique takes advantage of the fact that different classes of ferrite exhibit
      preferential grain boundary misorientations, aspect ratios and mean
      misorientation, all of which can be detected using current EBSD software. These
      characteristics are set as criteria for identification and linked to grain size
      to determine the area fractions. The results of this method were evaluated by
      comparing the new automated technique with point counting results. The technique
      could easily be applied to a range of other steel microstructures.

PMID- 24291696
TI  - Nurr1 expression is regulated by voltage-dependent calcium channels and
      calcineurin in cultured hippocampal neurons.
AB  - Nurr1 is an orphan nuclear transcription factor expressed in the brain. While
      Nurr1 is assumed to be an immediate early gene, it is not fully understood how
      Nurr1 expression is regulated in an activity-dependent manner in the central
      nervous system. Here, we investigated the molecular mechanisms underlying the
      regulation of Nurr1 expression in cultured hippocampal and cortical neurons. We
      found that upregulation of neural activity by high KCl and bicuculline enhances
      Nurr1 levels, while blockade of its activity by tetrodotoxin reduces Nurr1
      levels. The induction of Nurr1 expression was mediated by voltage-dependent
      calcium channels (VDCCs), as shown by cadmium and VDCC-specific inhibitors.
      Furthermore, calcineurin, but not calcium/calmodulin-dependent protein kinase
      (CaMK) was critical for the induction. Thus, Nurr1 expression is regulated by
      VDCC and calcineurin in a cell-autonomous, neural activity-dependent manner. 

PMID- 24291697
TI  - Neocortical integration of transplanted GABA progenitor cells from wild type and
      GABA(B) receptor knockout mouse donors.
AB  - Most cortical interneurons originate in a region of the embryonic subpallium
      called the medial ganglionic eminence (MGE). When MGE cells are transplanted into
      cerebral cortex, these progenitors migrate extensively and differentiate into
      functional inhibitory neurons. Although MGE progenitors have therapeutic
      potential following transplantation, it is unknown precisely how these cells
      distribute within neocortical lamina of the recipient brain. Here we transplanted
      mouse embryonic day 12.5 MGE progenitors into postnatal neocortex and evaluated
      laminar distribution of interneuron subtypes using double- and triple-label
      immunohistochemistry. Studies were performed using wild type (WT) or donor mice
      lacking a metabotropic GABA(B) receptor subunit (GABA(B1)R KO). MGE-derived
      neurons from WT and GABA(B1)R KO mice preferentially and densely distributed in
      neocortical layers 2/3, 5 and 6. As expected, MGE-derived neurons differentiated
      into parvalbumin+ and somatostatin+ interneurons within these neocortical lamina.
      Our findings provide insights into the anatomical integration of MGE-derived
      interneurons following transplantation.

PMID- 24291698
TI  - Dynamic changes of Apo A1 mediated by LXR/RXR/ABCA1 pathway in brains of the
      aging rats with cerebral hypoperfusion.
AB  - Cerebral hypoperfusion or aging often results into the disturbances of
      cholesterol and lipoprotein, which have been tightly associated with numerous
      neurological and psychiatric diseases, such as vascular dementia. The pathway of
      liver X receptor-beta (LXR-beta)/retinoic X receptor-alpha (RXR-alpha)/ABCA1
      plays a vital role in lipoprotein metabolism. However, there were no reports
      about the relationship between the signal molecules of the pathway and
      lipoprotein homeostasis in cerebral hypoperfusion models. Therefore, we aimed to
      detect the expression of the pathway molecules in the aging rat models of chronic
      cerebral hypoperfusion and to explore its underlying mechanism. The model with
      cerebral hypoperfusion was established by ligating of the bilateral common
      carotid arteries (2VO). The temporal blood flow in the model rats was
      significantly decreased 14 d, 21 d and 28 d after 2VO compared with the control.
      The serum levels of high-density lipoprotein (HDL) and total cholesterol (TC)
      were reached a peak at 14 d, then, they were gradually decreased. The changes of
      LXR-beta, RXR-alpha, ABCA1 and apolipoprotein A1 (apo A1) of the pathway were
      consistent with the changes of HDL and TC. We conclude that LXR-beta/RXR
      alpha/ABCA1 and downstream genes apo A1 undergo dynamic changes during the
      process of cerebral hypoperfusion. The LXR-beta/RXR-alpha/ABCA1 mediated apo A1
      cholesterol may play a protective effect, and the effect only exists in a certain
      period of time. 

PMID- 24291699
TI  - Paraplegia after staphylococcal sepsis.

PMID- 24291700
TI  - Undifferentiated sarcoma arising at lower thoracic spine with neuroblastoma-like
      dumbbell-shaped radiographic appearance in a 1-year-old girl.

PMID- 24291701
TI  - Biomechanical analysis of the upper thoracic spine after decompressive
      procedures.
AB  - BACKGROUND CONTEXT: Decompressive procedures such as laminectomy, facetectomy,
      and costotransversectomy are routinely performed for various pathologies in the
      thoracic spine. The thoracic spine is unique, in part, because of the
      sternocostovertebral articulations that provide additional strength to the region
      relative to the cervical and lumbar spines. During decompressive surgeries,
      stability is compromised at a presently unknown point. PURPOSE: To evaluate
      thoracic spinal stability after common surgical decompressive procedures in
      thoracic spines with intact sternocostovertebral articulations. STUDY DESIGN:
      Biomechanical cadaveric study. METHODS: Fresh-frozen human cadaveric spine
      specimens with intact rib cages, C7-L1 (n=9), were used. An industrial robot
      tested all spines in axial rotation (AR), lateral bending (LB), and flexion
      extension (FE) by applying pure moments (+/-5 Nm). The specimens were first
      tested in their intact state and then tested after each of the following
      sequential surgical decompressive procedures at T4-T5 consisting of laminectomy;
      unilateral facetectomy; unilateral costotransversectomy, and subsequently
      instrumented fusion from T3-T7. RESULTS: We found that in all three planes of
      motion, the sequential decompressive procedures caused no statistically
      significant change in motion between T3-T7 or T1-T12 when compared with intact.
      In comparing between intact and instrumented specimens, our study found that
      instrumentation reduced global range of motion (ROM) between T1-T12 by 16.3%
      (p=.001), 12% (p=.002), and 18.4% (p=.0004) for AR, FE, and LB, respectively. Age
      showed a negative correlation with motion in FE (r = -0.78, p=.01) and AR (r=
      0.7, p=.04). CONCLUSIONS: Thoracic spine stability was not significantly affected
      by sequential decompressive procedures in thoracic segments at the level of the
      true ribs in all three planes of motion in intact thoracic specimens. Age
      appeared to negatively correlate with ROM of the specimen. Our study suggests
      that thoracic spinal stability is maintained immediately after unilateral
      decompression at the level of the true ribs. These preliminary observations,
      however, do not depict the long-term sequelae of such procedures and warrant
      further investigation.

PMID- 24291702
TI  - Cauda equina and conus medullaris avulsion with herniation after midlumbar chance
      fracture.

PMID- 24291704
TI  - Selective removal of keratan sulfate in chondroitin sulfate samples by sequential
      precipitation with ethanol.
AB  - Keratan sulfate (KS) is present as a contaminant in chondroitin sulfate (CS)
      mainly extracted from shark cartilage. We report a selective removal procedure of
      KS in CS samples by means of sequential precipitation with ethanol. Purified
      shark CS containing approximately 10% to 15% KS was subjected to a precipitation
      procedure in the presence of increasing percentages of saturated ethanol. In
      contrast to other solvents, 1.0 volume of ethanol was able to selectively purify
      CS, with a purity of approximately 100%, from KS. The current selective and
      simple procedure appears to be a reliable industrial preparation of CS devoid of
      large amounts of the residual KS. 

PMID- 24291703
TI  - Intradiscal injection of simvastatin results in radiologic, histologic, and
      genetic evidence of disc regeneration in a rat model of degenerative disc
      disease.
AB  - BACKGROUND CONTEXT: A large percentage of back pain can be attributed to
      degeneration of the intervertebral disc (IVD). Bone morphogenetic protein 2 (BMP
      2) is known to play an important role in chondrogenesis of the IVD. Simvastatin
      is known to upregulate expression of BMP-2. Thus, we hypothesized that
      intradiscal injection of simvastatin in a rat model of degenerative disc disease
      (DDD) would result in retardation of DDD. PURPOSE: The purpose of the present
      study was to develop a novel conservative treatment for DDD and related
      discogenic back pain. STUDY DESIGN/SETTING: The setting of this study is the
      laboratory investigation. METHODS: Disc injury was induced in 272 rats via 21-ga
      needle puncture. After 6 weeks, injured discs were treated with simvastatin in a
      saline or hydrogel carrier. Rats were sacrificed at predetermined time points.
      Outcome measures assessed were radiologic, histologic, and genetic.
      Radiologically, the magnetic resonance imaging (MRI) index (number of pixels
      multiplied by the corresponding image densities) was determined. Histologically,
      disc spaces were read by three blinded scorers using a previously described
      histologic grading scale. Genetically, nuclei pulposi were harvested, and
      polymerase chain reaction was run to determine relative levels of aggrecan,
      collagen type II, and BMP-2 gene expression. RESULTS: Radiologically, discs
      treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI
      indices that were normal through 8 weeks after treatment, although this was more
      sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL
      of simvastatin in hydrogel demonstrated improved grades compared with discs
      treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin
      in hydrogel demonstrated higher gene expression of aggrecan and collagen type II
      than control. CONCLUSIONS: Degenerate discs treated with 5 mg/mL of simvastatin
      in a hydrogel carrier demonstrated radiographic and histologic features
      resembling normal noninjured IVDs. In addition, the gene expression of aggrecan
      and collagen type II (important constituents of the IVD extracellular matrix) was
      upregulated in treated discs. Injection of simvastatin into degenerate IVDs may
      result in retardation of disc degeneration and represents a promising
      investigational therapy for conservative treatment of DDD.

PMID- 24291705
TI  - Fluorescence-based temperature control for polymerase chain reaction.
AB  - The ability to accurately monitor solution temperature is important for the
      polymerase chain reaction (PCR). Robust amplification during PCR is contingent on
      the solution reaching denaturation and annealing temperatures. By correlating
      temperature to the fluorescence of a passive dye, noninvasive monitoring of
      solution temperatures is possible. The temperature sensitivity of 22 fluorescent
      dyes was assessed. Emission spectra were monitored and the change in fluorescence
      between 45 and 95 degrees C was quantified. Seven dyes decreased in intensity as
      the temperature increased, and 15 were variable depending on the excitation
      wavelength. Sulforhodamine B (monosodium salt) exhibited a fold change in
      fluorescence of 2.85. Faster PCR minimizes cycling times and improves turnaround
      time, throughput, and specificity. If temperature measurements are accurate, no
      holding period is required even at rapid speeds. A custom instrument using
      fluorescence-based temperature monitoring with dynamic feedback control for
      temperature cycling amplified a fragment surrounding rs917118 from genomic DNA in
      3min and 45s using 35 cycles, allowing subsequent genotyping by high-resolution
      melting analysis. Gold-standard thermocouple readings and fluorescence-based
      temperature differences were 0.29+/-0.17 and 0.96+/-0.26 degrees C at annealing
      and denaturation, respectively. This new method for temperature cycling may allow
      faster speeds for PCR than currently considered possible. 

PMID- 24291706
TI  - External quality assurance programs as a tool for verifying standardization of
      measurement procedures: Pilot collaboration in Europe.
AB  - INTRODUCTION: Current external quality assurance schemes have been classified
      into six categories, according to their ability to verify the degree of
      standardization of the participating measurement procedures. SKML (Netherlands)
      is a Category 1 EQA scheme (commutable EQA materials with values assigned by
      reference methods), whereas SEQC (Spain) is a Category 5 scheme (replicate
      analyses of non-commutable materials with no values assigned by reference
      methods). AIM: The results obtained by a group of Spanish laboratories
      participating in a pilot study organized by SKML are examined, with the aim of
      pointing out the improvements over our current scheme that a Category 1 program
      could provide. METHOD: Imprecision and bias are calculated for each analyte and
      laboratory, and compared with quality specifications derived from biological
      variation. RESULTS: Of the 26 analytes studied, 9 had results comparable with
      those from reference methods, and 10 analytes did not have comparable results.
      The remaining 7 analytes measured did not have available reference method values,
      and in these cases, comparison with the peer group showed comparable results. The
      reasons for disagreement in the second group can be summarized as: use of non
      standard methods (IFCC without exogenous pyridoxal phosphate for AST and ALT,
      Jaffe kinetic at low-normal creatinine concentrations and with eGFR); non
      commutability of the reference material used to assign values to the routine
      calibrator (calcium, magnesium and sodium); use of reference materials without
      established commutability instead of reference methods for AST and GGT, and lack
      of a systematic effort by manufacturers to harmonize results. CONCLUSIONS:
      Results obtained in this work demonstrate the important role of external quality
      assurance programs using commutable materials with values assigned by reference
      methods to correctly monitor the standardization of laboratory tests with
      consequent minimization of risk to patients.

PMID- 24291707
TI  - Common decision limits --The need for harmonised immunoassays.
AB  - The main aim of clinical guidelines is to encourage the best clinical outcome for
      patients and the best use of resources, no matter where patients are investigated
      or managed. Where guidelines incorporate decision limits based on levels of
      analytes in serum, plasma or urine these may determine whether or not to treat or
      may be used to tailor further treatment. Consideration should be given to the
      effect of method-related differences in results when implementing common decision
      limits. Available evidence suggests that for some analytes the implications for
      the patient may be serious, e.g. in terms of missed biopsies or unnecessary
      prostatic biopsies when prostate specific antigen is measured. Major causes of
      between-method differences are reviewed and means of addressing them considered.

PMID- 24291708
TI  - 1H NMR spectroscopic studies establish that heparanase is a retaining
      glycosidase.
AB  - Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate side chains
      of proteoglycans in basement membranes and the extracellular matrix (ECM).
      Heparanase is implicated in several diverse pathological processes associated
      with ECM degradation such as metastasis, inflammation and angiogenesis and is
      thus an important target for anti-cancer and anti-inflammatory drug discovery.
      Heparanase has been classed as belonging to the clan A glycoside hydrolase family
      79 based on sequence analysis, secondary structure predictions and mutagenic
      analysis, and thus it has been inferred that it is a retaining glycosidase.
      However, there has been no direct experimental evidence to support this
      conclusion. Herein we describe (1)H NMR spectroscopic studies of the hydrolysis
      of the pentasaccharide substrate fondaparinux by heparanase, and provide
      conclusive evidence that heparanase hydrolyses its substrate with retention of
      configuration and is thus established as a retaining glycosidase. Knowledge of
      the mechanism of hydrolysis may have implications for future design of inhibitors
      for this important drug target. 

PMID- 24291709
TI  - The human cathelicidin LL-37 enhances airway mucus production in chronic
      obstructive pulmonary disease.
AB  - Airway mucus overproduction is a distinguishing feature of chronic obstructive
      pulmonary disease (COPD). LL-37 is the only member of human cathelicidins family
      of antimicrobial peptides and plays a central role in many immune and
      inflammatory reactions. Increasing evidence suggests the involvement of LL-37 in
      the pathogenesis of COPD. Here, we investigated the effects of LL-37 on airway
      mucus overproduction in COPD. We observed overexpression of both LL-37 and MUC5AC
      mucin (a major mucin component of mucus) in airways of COPD patients and found a
      correlation between them. We showed in vitro that LL-37 induces MUC5AC mucin
      production by airway epithelial NCI-H292 cells in the absence and presence of
      cigarette smoke extract, with TNF-alpha converting enzyme (TACE)-EGFR-ERK1/2
      pathway and IL-8 required for the induction. Therefore, we concluded that LL-37
      enhances the mucus production in COPD airways, thus contributing to the
      progression of COPD. 

PMID- 24291710
TI  - Pre-pore oligomer formation by Vibrio cholerae cytolysin: insights from a
      truncated variant lacking the pore-forming pre-stem loop.
AB  - Vibrio cholerae cytolysin (VCC), a beta-barrel pore-forming toxin (beta-PFT),
      induces killing of the target eukaryotic cells by forming heptameric
      transmembrane beta-barrel pores. Consistent with the beta-PFT mode of action,
      binding of the VCC toxin monomers with the target cell membrane triggers
      formation of pre-pore oligomeric intermediates, followed by membrane insertion of
      the beta-strands contributed by the pre-stem motif within the central cytolysin
      domain of each protomer. It has been shown previously that blocking of membrane
      insertion of the VCC pre-stem motif arrests conversion of the pre-pore state to
      the functional transmembrane pore. Consistent with the generalized beta-PFT
      mechanism, it therefore appears that the VCC pre-stem motif plays a critical role
      toward forming the structural scaffold of the transmembrane beta-barrel pore. It
      is, however, still not known whether the pre-stem motif plays any role in the
      membrane interaction process, and subsequent pre-pore structure formation by VCC.
      In this direction, we have constructed a recombinant variant of VCC deleting the
      pre-stem region, and have characterized the effect(s) of physical absence of the
      pre-stem motif on the distinct steps of the membrane pore-formation process. Our
      results show that the deletion of the pre-stem segment does not affect membrane
      binding and pre-pore oligomer formation by the toxin, but it critically abrogates
      the functional pore-forming activity of VCC. Present study extends our insights
      regarding the structure-function mechanism associated with the membrane pore
      formation by VCC, in the context of the beta-PFT mode of action. 

PMID- 24291711
TI  - The measurement of visual sampling during real-world activity in Parkinson's
      disease and healthy controls: a structured literature review.
AB  - BACKGROUND: Visual sampling techniques are used to investigate the complex role
      of vision during real-world activities in Parkinson's disease. Earlier research
      is limited to static simple tasks or measurement of eye movements alone, but more
      recent investigations involve more real-world activities. The approach to the
      objective measurement of eye movements varies with respect to instrumentation,
      testing protocols, and mediating factors that may influence visual sampling.
      OBJECTIVES: The aim of this review was to examine previous work measuring visual
      sampling during real-world activities in Parkinson's disease to inform the
      development of robust protocols. Within this review a real-world activity was
      considered to be a goal-orientated motor task involving more than one body
      segment such as reaching or walking. METHODS: Medline, Embase, PsychInfo, Scopus,
      Web of Knowledge, PubMed and the Cochrane library databases were searched. Two
      independent reviewers and an adjudicator screened articles that described
      quantitative visual sampling in people with Parkinson's disease and healthy
      controls. RESULTS: Twenty full-text articles were screened and 15 met
      inclusion/exclusion criteria. A wide range of instruments and outcome measures
      were reported which were generally used in a task-dependent manner. Instrument
      reliability and validity was insufficiently reported in all studies. Few studies
      considered mediators of visual sampling such as visual or cognitive deficits.
      CONCLUSIONS: Future research is required to accurately characterise visual
      impairments in Parkinson's disease and during real-world activities. Composite
      use of instruments may be required to achieve reliability and validity of visual
      sampling outcomes which need to be standardised. Recommendations also include
      assessment of cognition and basic visual function.

PMID- 24291714
TI  - Cost of immune priming within generations: trade-off between infection and
      reproduction.
AB  - Immune priming is a new paradigm in innate immunity. However, most studies have
      focused on the benefits of priming (enhanced survival and parasite clearance
      after a second challenge), while little attention has been paid to the costs. In
      this study, both factors were investigated in Anopheles albimanus primed against
      Plasmodium berghei. As previously observed in other invertebrates, compared to un
      primed mosquitoes, those primed better controlled a challenge from the same
      parasite, and had a higher survival rate. Although there was no difference in the
      number of oviposited eggs between primed and control females, hatching rate was
      lower in primed than in control mosquitoes and it was more likely for control
      females to produce eggs than for primed females. Furthermore, a trade-off between
      parasite elimination and egg production was observed among primed mosquitoes, as
      primed females that successfully fought the infection were unable to produce
      eggs, but primed females that produced eggs were similarly infected as control un
      primed ones. These results concord with recent mathematical models suggesting
      that reproduction affects immune priming outcomes, and may explain why in some
      species and under some conditions it seems that immune priming is not occurring.

PMID- 24291712
TI  - Learning optimal eye movements to unusual faces.
AB  - Eye movements, which guide the fovea's high resolution and computational power to
      relevant areas of the visual scene, are integral to efficient, successful
      completion of many visual tasks. How humans modify their eye movements through
      experience with their perceptual environments, and its functional role in
      learning new tasks, has not been fully investigated. Here, we used a face
      identification task where only the mouth discriminated exemplars to assess if,
      how, and when eye movement modulation may mediate learning. By interleaving
      trials of unconstrained eye movements with trials of forced fixation, we
      attempted to separate the contributions of eye movements and covert mechanisms to
      performance improvements. Without instruction, a majority of observers
      substantially increased accuracy and learned to direct their initial eye
      movements towards the optimal fixation point. The proximity of an observer's
      default face identification eye movement behavior to the new optimal fixation
      point and the observer's peripheral processing ability were predictive of
      performance gains and eye movement learning. After practice in a subsequent
      condition in which observers were directed to fixate different locations along
      the face, including the relevant mouth region, all observers learned to make eye
      movements to the optimal fixation point. In this fully learned state, augmented
      fixation strategy accounted for 43% of total efficiency improvements while covert
      mechanisms accounted for the remaining 57%. The findings suggest a critical role
      for eye movement planning to perceptual learning, and elucidate factors that can
      predict when and how well an observer can learn a new task with unusual
      exemplars. 

PMID- 24291715
TI  - Determination of carbadox and olaquindox metabolites in swine muscle by liquid
      chromatography/mass spectrometry.
AB  - This paper presents LC-MS/MS method that was developed for the simultaneous
      determination and confirmation metabolites of carbadox (desoxycarbadox,
      quinoxaline-2-carboxylic) and olaquindox (3-methylquinoxaline-2-carboxylic acid)
      residues in pig muscle tissues at concentrations <=3.0MUgkg(-1). Pig muscle
      tissues were deproteinated with meta-phosphoric acid in methanol and then were
      extracted with ethyl acetate:dichloromethane (50:50, v/v). The whole extracts
      were evaporated to dryness in rotary evaporator at 45 degrees C, and dry residues
      were re-dissolved in 0.5% isopropanol in 1% acetic acid. The LC separation was
      performed on a C8 column with a gradient system consisting of
      isopropanol/water/acetic acid and methanol as the mobile phase. Additionally
      SelexIONTM technology to reduce matrix effect was used. The decision limit
      (CCalpha) ranged from 1.04MUgkg(-1) to 2.11MUgkg(-1) and the detection capability
      (CCbeta) ranged from 1.46MUgkg(-1) to 2.89MUgkg(-1). The total recoveries were
      from 99.8% to 101.2%. The results of validation fulfil the requirement of the
      confirmatory criteria according to the European Commission Decision 2002/657/EC. 

PMID- 24291713
TI  - A vaccine formulated with a combination of TLR-2 and TLR-9 adjuvants and the
      recombinant major outer membrane protein elicits a robust immune response and
      significant protection against a Chlamydia muridarum challenge.
AB  - Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen
      in the World and there is a need for a vaccine. To enhance the immunogenicity of
      a vaccine formulated with the Chlamydia muridarum (Cm) mouse pneumonitis
      recombinant major outer membrane protein (MOMP), we used combinations of Pam2CSK4
      + CpG-1826 and Montanide ISA 720 VG + CpG-1826 as adjuvants. Neisseria
      gonorrhoeae recombinant porin B (Ng-PorB) was used as the antigen control with
      the same adjuvants. Female BALB/c mice were immunized twice in the nares (i.n.)
      or in the colon (cl.) and were boosted twice by the intramuscular plus
      subcutaneous (i.m. + s.c.) routes. Based on the IgG2a/IgG1 ratio in sera, mice
      immunized with MOMP + Pam2CSK4 + CpG-1826 showed a strong Th2 response while
      animals vaccinated with MOMP + Montanide ISA 720 VG + CpG-1826 had a Th1
      response. Both groups of mice also developed robust Cm-specific T cell
      proliferation and high levels of IFN-gamma. Four weeks after the last
      immunization, the mice were challenged i.n. with 10(4) inclusion-forming units
      (IFU) of Cm. Using changes in body weight and number of IFU recovered from the
      lungs at 10 days post-challenge mice immunized i.n. + i.m./s.c. with MOMP +
      Pam2CSK4 + CpG-1826 were better protected than other groups. In conclusion, MOMP
      adjuvanted with Pam2CSK4 + CpG-1826, elicits strong humoral and cellular immune
      responses and induces significant protection against Chlamydia.

PMID- 24291716
TI  - Purification of antibiotics from the biocontrol agent Streptomyces anulatus S37
      by centrifugal partition chromatography.
AB  - A novel actinomycete strain, Streptomyces anulatus S37, has been isolated from
      the rhizosphere of healthy Moroccan Vitis vinifera on the basis on its ability to
      promote grapevine growth and to induce natural defences against various
      phytopathogens. In the present work, the main bioactive metabolites produced by
      S. anulatus S37 were isolated. A crude n-BuOH extract of the S37 fermentation
      broth was firstly partitioned in a biphasic solvent system composed of n-heptane,
      methanol, and water (5:1.5:3.5, v/v). The most active organic fraction (1.1g) as
      revealed by TLC-bioautography was subsequently separated by a two-step
      centrifugal partition chromatography procedure. The first separation was
      performed in the ascending mode at 6mL/min with the biphasic solvent system n
      heptane, ethyl acetate, methanol and water (2:1:2:1, v/v), to finally recover
      40mg of a pure compound identified as streptochlorin by NMR spectroscopy. In a
      second separation, the solvent system n-heptane, acetonitrile, and water (5:5:4,
      v/v) was used in the ascending mode at 3mL/min to purify 135mg of nigericin and
      53mg of piericidin A1. Assays performed with the three compounds have confirmed
      their inhibitory impact on the growth of Botryris cinerea in dual confrontation
      and also on V. vinifera L. plantlets. 

PMID- 24291717
TI  - Determination of sec-O-glucosylhamaudol in rat plasma by gradient elution liquid
      chromatography-mass spectrometry.
AB  - Sec-O-glucosylhamaudol is one of the major bioactive compounds of the
      Saposhnikoviae Radix. A simple and selective liquid chromatography-mass
      spectrometry (LC-MS) method for determination of sec-O-glucosylhamaudol in rat
      plasma was developed. After addition of carbamazepine as internal standard (IS),
      protein precipitation with acetonitrile-methanol (9:1, v/v) was used as sample
      preparation. Chromatographic separation was achieved on a Zorbax SB-C18
      (2.1mm*150mm, 5MUm) column with acetonitrile-0.1% formic acid in water as mobile
      phase with gradient elution. Electrospray ionization (ESI) source was applied and
      operated in positive ion mode; selective ion monitoring (SIM) mode was used for
      quantification using target fragment ions m/z 439 for sec-O-glucosylhamaudol and
      m/z 237 for the IS. Calibration plots were linear over the range of 50-8000ng/mL
      for sec-O-glucosylhamaudol in rat plasma. Mean recovery of sec-O-glucosylhamaudol
      in plasma was in the range of 74.8-83.7%. Intra-day and inter-day precision were
      both <15%. This method was successfully applied in pharmacokinetic study after
      intravenous administration of 2.5mg/kg sec-O-glucosylhamaudol in rats. 

PMID- 24291718
TI  - Negative pseudo-affinity chromatography for plasmid DNA purification using
      berenil as ligand.
AB  - The present study, reports the utilization of berenil as ligand in a negative
      pseudo-affinity chromatographic step to purify the plasmid pVAX1-LacZ from
      Escherichia coli clarified lysates. The chromatographic support was prepared by
      coupling berenil to epoxy-activated Sepharose and was qualitatively and
      quantitatively characterized using scanning electron microscopy, Fourier
      transformed infrared spectroscopy and elemental analysis. The clarified lysate
      was loaded onto the berenil-Sepharose support with 0.55M of ammonium sulphate in
      the eluent, achieving the immediate elution of plasmid DNA. The impurities
      tightly bound to the support, were eluted after decreasing the salt concentration
      to 0M. The overall process enabled the recovery of 87% of loaded plasmid DNA with
      a HPLC purity of ?99% and according to FDA specifications. This method represents
      an alternative approach to the previous utilization of the same chromatographic
      pseudo-affinity support in a positive mode. It uses lower amounts of salt and one
      step chromatographic procedure, resulting in smaller operating time and costs and
      representing an alternate procedure for plasmid DNA purification. 

PMID- 24291719
TI  - Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence
      detector coupled with strong cation exchange chromatographic column: application
      to a pharmacokinetic study in Chinese healthy volunteers.
AB  - A simple, selective, and sensitive high performance liquid chromatography (HPLC)
      procedure has been developed for determination of trazodone in human plasma.
      Prazosin was employed as the internal standard (IS). Sample preparation involved
      liquid-liquid extraction by methyl tert-butyl ether after alkalinization with
      ammonia. The HPLC separation was performed on a CAPCELL PAK SCX column
      (250mm*4.6mm, 5.0MUm, Shiseido, Japan) with a mobile phase of
      acetonitrile/80mmol/L ammonium phosphate (pH adjusted to 6.0) (60:40, v/v) at a
      flow rate of 1.2mL/min. The peaks were detected by using fluorescence detector
      (excitation wavelength 320nm and emission wavelength 440nm). The extraction
      recovery was 72.6-88.3% and the method was over the concentration range of 5.0
      2486ng/mL with a lower limit of quantitation (LLOQ) of 5.0ng/mL using 300MUL of
      plasma. The intra- and inter-day accuracy of the method at three concentrations
      ranged from 96.7% to 104.2% for trazodone with precision of 2.9-3.7%. This
      validated method was successfully applied to a pharmacokinetic study enrolling 12
      Chinese volunteers administered a single oral trazodone hydrochloride extended
      release tablet of 75mg. 

PMID- 24291720
TI  - Development and validation of a LC-MS/MS method for homocysteine thiolactone in
      plasma and evaluation of its stability in plasma samples.
AB  - The present study demonstrates the development and validation of a sensitive
      method for the quantification of homocysteine thiolactone (HCTL) in human plasma
      using the technique of LC-MS/MS. The gradient elution of HCTL was achieved within
      5min using ZIC HILIC column having acetonitrile with 0.1% formic acid and water
      with 0.1% formic acid. The method was validated for the linearity, sensitivity,
      accuracy, precision, recovery, matrix effect and stability. A good linearity was
      found within a range of 0.5-32.5nmol/ml. Quantification was performed using
      multiple reaction monitoring (MRM) mode based on the molecular/fragment ion
      transitions for HCTL (118/56) and homatropine (276.1/142.2) as internal standard.
      Generally, HCTL levels in plasma were found to be highly unstable. In order to
      verify the stability of the HCTL levels in plasma for a longer period, the
      samples were extracted immediately and stored at -86 degrees C. Using the above
      method it was found to be stable for a period of 1 month. The method was well
      applied for quantification of HCTL in plasma of healthy human volunteers. 

PMID- 24291721
TI  - Adduct formation in liquid chromatography-triple quadrupole mass spectrometric
      measurement of bryostatin 1.
AB  - Bryostatin 1, a potential anti-Alzheimer drug, is effective at subnanomolar
      concentrations. Measurement is complicated by the formation of low m/z
      degradation products and the formation of adducts with various cations, which
      make accurate quantitation difficult. Adduct formation caused the sample matrix
      or mobile phase to partition bryostatin 1 into products of different mass.
      Degradation of the 927 [M+Na](+) ion to a 869m/z product was strongly influenced
      by ionization conditions. We validated a bryostatin 1 assay in biological tissues
      using capillary column HPLC with nanospray ionization (NSI) in a triple
      quadrupole mass spectrometer in selected reaction monitoring (SRM) mode. Adduct
      formation was controlled by adding 1mM acetic acid and 0.1mM sodium acetate to
      the HPLC buffer, maximizing the formation of the [M+Na](+) ion. Efficient removal
      of contaminating cholesterol from the sample during solvent extraction was also
      critical. The increased sensitivity provided by NSI and capillary-bore columns
      and the elimination of signal partitioning due to adduct formation and
      degradation in the ionization source enabled a detection limit of 1*10(-18)mol of
      bryostatin 1 and a LLOQ of 3*10(-18)mol from 1MUl of sample. Bryostatin 1 at low
      pmol/l concentrations enabled measurement in brain and other tissues without the
      use of radioactive labels. Despite bryostatin 1's high molecular weight,
      considerable brain access was observed, with peak brain concentrations exceeding
      8% of the peak blood plasma concentrations. Bryostatin 1 readily crosses the
      blood-brain barrier, reaching peak concentrations of 0.2nM, and specifically
      activates and translocates brain PKCE. 

PMID- 24291722
TI  - Determination of warfarin alcohols by ultra-high performance liquid
      chromatography-tandem mass spectrometry: application to in vitro enzyme kinetic
      studies.
AB  - A sensitive, accurate, and reproducible ultra-high performance liquid
      chromatography-tandem mass spectrometry method was developed and validated for
      determination of warfarin and its alcohol metabolites (RS/SR- and RR/SS-warfarin
      alcohol) in 10mM Tris-HCl incubation buffer (pH 7.4). Sample preparation involved
      acidification with 4% formic acid, followed by liquid-liquid extraction using
      methyl tert-butyl ether. Chromatographic separation was achieved using a Hypersil
      Gold C18 (2.1mm*100mm, 1.9MUm) analytical column with gradient elution of solvent
      A (water containing 0.01% formic acid) and solvent B (acetonitrile containing
      0.1% formic acid). The flow rate was 0.4mL/min and the total run time was 5min.
      Detection of analytes was performed using heated electrospray ionization
      (negative mode) and selected reaction monitoring. Excellent linearity was
      observed for all analytes over the standard curve concentration ranges of 100
      10,000ng/mL for warfarin, and 0.5-250ng/mL for warfarin alcohols. The intra- and
      inter-day accuracy and precision for analytes were within +/-10.0%. Excellent
      recovery and negligible matrix effects were observed. The method is robust,
      sensitive, accurate and reproducible, and was successfully applied to in vitro
      enzyme kinetic studies of warfarin. 

PMID- 24291723
TI  - Quantification of free sialic acid in human plasma through a robust quinoxalinone
      derivatization and LC-MS/MS using isotope-labeled standard calibration.
AB  - We report an accurate quantification of free sialic acid (SA) in human plasma
      using LC-MS/MS method with isotope-labeled standard calibration (ILSC) and robust
      derivatization. Specifically, derivatization of SA with a stable and inexpensive
      3,4-diaminotoluene (DAT) provides a stable product of SA with high MS response,
      proving a convenient and cost-effective LC-MS/MS analysis of free SA. In
      addition, the use of (13)C3-SA as calibration standard ensured the accuracy for
      the measurement. This assay used ultra high performance liquid chromatography
      (UHPLC) for separation of native/labeled SA and IS from matrix interference, and
      employed mass spectrometry in multiple reaction monitoring (MRM) mode for
      sensitive and selective detection. We have achieved a lower limit of
      quantification (LLOQ) of 20ng/mL and a total running time of 4.2min, which is the
      most sensitive and quick measurement for free SA in biomatrices. 

PMID- 24291724
TI  - Stress-dependent opioid and adrenergic modulation of newly retrieved fear memory.
AB  - Recent studies on the effect of stress on modulation of fear memory in our
      laboratory have uncovered endogenous opioid and adrenergic based modulation
      systems, working in concert, that limit the strengthening or weakening of newly
      acquired fear memory during consolidation under conditions of mild or intense
      stress, respectively. The present study sought to determine if similar stress
      dependent modulation, mediated by endogenous opioid and adrenergic systems,
      occurs during reconsolidation of newly retrieved fear memory. Rats underwent
      contextual fear conditioning followed 24h later by reactivation of fear memory; a
      retention test was administered the next day. Stress was manipulated by varying
      duration of recall of fear memory during reactivation. In the first experiment,
      vehicle or the opioid-receptor blocker naloxone was administered immediately
      after varied durations (30 or 120 s) of reactivation. The results indicate that
      (1) reactivation, in the absence of drug, has a marked effect on freezing
      behavior-as duration of reactivation increases from 30 to 120 s, freezing
      behavior and presumably fear-induced stress increases and (2) naloxone,
      administered immediately after 30 s (mild stress) or 120 s (intense stress) of
      reactivation, enhances or impairs retention, respectively, the next day. In the
      second experiment, naloxone and the beta-adrenergic blocker propranolol were
      administered either separately or in combination immediately after 120 s (intense
      stress) reactivation. The results indicate that separate administration of
      propranolol and naloxone impairs retention, while the combined administration
      fails to do so. Taken together the results of the two experiments are consistent
      with a protective mechanism, mediated by endogenous opioid and adrenergic systems
      working in concert, that limits enhancement and impairment of newly retrieved
      fear memory during reactivation in a stress-dependent manner.

PMID- 24291726
TI  - Characterization of human auditory brainstem circuits by calcium-binding protein
      immunohistochemistry.
AB  - The cochlear nucleus (CN) and superior olivary complex are auditory brainstem
      centers with essential roles in encoding temporal features of vocalizations,
      localization of sound sources and descending modulation of the cochlea. Numerous
      neuronal populations, across a multitude of laboratory mammals, have been
      characterized within these brainstem centers based on cell body morphology,
      dendritic architecture, afferent/efferent connections and neurochemistry.
      However, scant details are available for these neuronal populations in humans.
      The objective of this study is to further characterize human auditory hindbrain
      nuclei and examine the axonal connections between these structures. To this end,
      we have used immunohistochemistry and morphometric techniques to characterize
      neuronal populations and axonal projections in the human brainstem. Herein, we
      provide evidence for calretinin immunoreactive neurons and synaptic boutons in
      the ventral CN, axons in the trapezoid body, peridendritic boutons in the medial
      superior olive and calyceal endings in the medial nucleus of the trapezoid body
      (MNTB). Further, we demonstrate that the majority of neurons in the human MNTB
      are calbindin and Kv3.1b immunoreactive and that perisomatic profiles in this
      nucleus are vesicular glutamate transporter and Rab3a positive, suggesting that
      such profiles are in fact synaptic terminals. 

PMID- 24291725
TI  - Comparative study of the neurotrophic effects elicited by VEGF-B and GDNF in
      preclinical in vivo models of Parkinson's disease.
AB  - Vascular endothelial growth factor B (VEGF-B) has recently been shown to be a
      promising novel neuroprotective agent for several neurodegenerative conditions.
      In the current study we extended previous work on neuroprotective potential for
      Parkinson's disease (PD) by testing an expanded dose range of VEGF-B (1 and 10
      MUg) and directly comparing both neuroprotective and neurorestorative effects of
      VEGF-B in progressive unilateral 6-hydroxydopamine (6-OHDA) PD models to a single
      dose of glial cell line-derived neurotrophic factor (GDNF, 10 MUg), that has been
      established by several groups as a standard in both preclinical PD models. In the
      amphetamine-induced rotational tests the treatment with 1 and 10 MUg VEGF-B
      resulted in significantly improved motor function of 6-OHDA-lesioned rats
      compared to vehicle-treated 6-OHDA-lesioned rats in the neuroprotection paradigm.
      Both doses of VEGF-B caused an increase in tyrosine hydroxylase (TH)-positive
      cell and fiber count in the substantia nigra (SN) and striatum in the
      neuroprotective experiment. The effect size was comparable to the effects seen
      with GDNF. In the neurorestoration paradigm, VEGF-B injection had no significant
      effect in either the behavioral or the immunohistochemical analyses, whereas GDNF
      injection significantly improved the amphetamine-induced rotational behavior and
      reduced TH-positive neuronal cell loss in the SN. We also present a strong
      positive correlation (p=1.9e-50) of the expression of VEGF-B with nuclear-encoded
      mitochondrial genes involved in fatty acid metabolism in rat midbrain, pointing
      to the mitochondria as a site of action of VEGF-B. GDNF showed a positive
      correlation with nuclear-encoded mitochondrial genes that was not nearly as
      strong (p=0.018). VEGF-B counteracted rotenone-induced reduction of (a) fatty
      acid transport protein 1 and 4 levels and (b) both Akt protein and
      phosphorylation levels in SH-SY5Y cells. We further verified VEGF-B expression in
      the human SN pars compacta of healthy controls and PD patients, in neuronal cells
      that show co-expression with neuromelanin. These results have demonstrated that
      VEGF-B has potential as a neuroprotective agent for PD therapy and should be
      further investigated.

PMID- 24291727
TI  - The subthalamic activity and striatal monoamine are modulated by subthalamic
      stimulation.
AB  - AIMS: Not all the mechanisms by which subthalamic nucleus deep brain stimulation
      (STN-DBS) alleviates parkinsonian symptoms have been clarified as yet. The levels
      of striatal monoamine and the subthalamic beta activity might contribute to its
      efficacy. However, their direct relationship is unclear. We aimed to examine the
      correlation between the striatal monoamine and the STN beta activity induced by
      STN-DBS. EXPERIMENTAL PROCEDURES: Experiments were performed under urethane
      anesthesia in normal (n=4) and 6-hydroxydopamine hemi-lesioned Parkinson's
      disease (PD) model rats (n=5). STN-DBS was applied to the left STN, and local
      field potential (LFP) was recorded before and after STN-DBS. Striatal
      extracellular fluid was collected before, during, and after STN-DBS. Spectral
      analysis of STN-LFP was performed, and the levels of monoamine were measured.
      RESULTS: The levels of 3-4-dihydroxyphenylacetic acid (DOPAC) were significantly
      decreased after the cessation of stimulation in PD model rats. The levels of none
      of the monoamines were significantly affected in normal rats. The STN beta power
      was significantly elevated after the cessation of stimulation in normal rats but
      was significantly decreased in PD model rats. The STN beta power and the levels
      of DOPAC and 5-HT was positively correlated in PD model rats, whereas the levels
      of dopamine and 5-HT showed positive correlation and the levels of DOPAC and
      Homovanillic acid (HVA) showed negative correlation in normal rats. CONCLUSION:
      STN-DBS could decrease the levels of DOPAC and the STN beta power in a PD model
      rat. The STN beta power and the levels of striatal monoamine might be
      differentially correlated between normal and PD model rats.

PMID- 24291728
TI  - Behavioral and neurophysiological investigation of the influence of verbal
      suggestion on tactile perception.
AB  - Recently we demonstrated that it is possible to influence tactile perception by
      applying a placebo manipulation consisting of verbal suggestion and conditioning
      and that this influence is associated to changes in the late components (N140 and
      P200) of somatosensory-evoked potentials (SEPs) (Fiorio et al., 2012). Due to the
      powerful effects of words in changing symptoms perception in the clinical domain,
      aim of this study was to investigate whether even in the tactile modality,
      perception can be changed by the mere use of persuasive words in a specific
      context. To this purpose, we adopted the same experimental setting of our
      previous study, apart from the conditioning procedure. A group of subjects
      (experimental group) has been verbally suggested about the effect of an inert
      cream in enhancing tactile perception, while a control group was informed about
      the inefficacy of the cream. In order to unveil the neurophysiological
      underpinnings of this effect, we compared the amplitude of late SEPs (P100, N140,
      P200), before and after treatment. Results showed that the experimental group did
      not perceive an increase of tactile sensation after the treatment and no
      modification occurred in the late SEPs. This study proves that verbal suggestion
      alone is not sufficient to induce enhanced tactile perception (at least with this
      experimental setting), suggesting that a conditioning procedure may be necessary
      in the tactile modality. The absence of changes in the late SEP components could
      reflect the lack of strong expectation following the placebo procedure. 

PMID- 24291729
TI  - Effects of congenital blindness on the subcortical representation of speech cues.
AB  - Human modalities play a vital role in the way the brain produces mental
      representations of the world around us. Although congenital blindness limits the
      understanding of the environment in some aspects, blind individuals may have
      other superior capabilities from long-term experience and neural plasticity. This
      study investigated the effects of congenital blindness on temporal and spectral
      neural encoding of speech at the subcortical level. The study included 26
      congenitally blind individuals and 24 normal-sighted individuals with normal
      hearing. Auditory brainstem response (ABR) was recorded with both click and
      speech synthetic 40-ms /da/ stimuli. No significant difference was observed
      between the two groups in wave latencies or amplitudes of click ABR. Latencies of
      speech ABR D (p=0.012) and O (p=0.014) waves were significantly shorter in blind
      individuals than in normal-sighted individuals. Amplitudes of the A (p<0.001) and
      E (p=0.001) speech ABR (sABR) waves were also significantly higher in blind
      subjects. Blind individuals had significantly better results for duration
      (p<0.001) amplitude (p=0.015) and slope of the V-A complex (p=0.004), signal-to
      noise ratio (p<0.001), and amplitude of the stimulus fundamental frequency (F0)
      (p=0.009), first formant (F1) (p<0.001) and higher-frequency region (HF)
      (p<0.001) ranges. Results indicate that congenitally blind subjects have improved
      hearing function in response to the /da/ syllable in both source and filter
      classes of sABR. It is possible that these subjects have enhanced neural
      representation of vocal cord vibrations and improved neural synchronization in
      temporal encoding of the onset and offset parts of speech stimuli at the
      brainstem level. This may result from the compensatory mechanism of neural
      reorganization in blind subjects influenced from top-down corticofugal
      connections with the auditory cortex. 

PMID- 24291731
TI  - Parental discussion of G6PD deficiency and child health: implications for
      clinical practice.
AB  - OBJECTIVE: Parents are encouraged to discuss self-care with children affected by
      G6PD deficiency; however, little is known about the extent or impact of these
      discussions on the physical and psychosocial health of these children. The
      purpose of this study was to examine the nature of parental-child discussions of
      G6PD deficiency self-care and their relationship to child health. METHODS: A
      quantitative cross-sectional survey of 178 Taiwanese parents of children with
      G6PD deficiency was conducted. The extent of parental-child self-care discussions
      was assessed in regards to coverage of nine key topics. Parent's G6PD deficiency
      status, knowledge of haemolytic anaemia symptoms and reported G6PD deficiency
      education from providers were examined as correlates of parental discussion.
      Child health was assessed with the child health questionnaire-parent form
      (Chinese version) and a 13-item haemolytic anaemia symptom list. RESULTS: Self
      care discussions were positively correlated with parental G6PD deficiency status
      (beta=2.08, p=0.03), accurate identification of haemolytic anaemia symptoms
      (beta=0.18, p=0.01), the thoroughness and clarity of patient education
      (beta=0.14, p<0.001) and child age (beta=1.04, p<0.001). Among children reported
      to have experienced significant symptoms of acute haemolytic anaemia (35%), the
      extent of self-care discussions was positively associated with reported physical
      and psychosocial child health (beta=1.18, p<0.001). CONCLUSIONS: Parental-child
      G6PD deficiency self-care discussions are associated with better child health,
      and parental involvement in these discussions is facilitated by the thoroughness
      and clarity of patient education received from providers.

PMID- 24291730
TI  - Role of myelin plasticity in oscillations and synchrony of neuronal activity.
AB  - Conduction time is typically ignored in computational models of neural network
      function. Here we consider the effects of conduction delays on the synchrony of
      neuronal activity and neural oscillators, and evaluate the consequences of
      allowing conduction velocity (CV) to be regulated adaptively. We propose that CV
      variation, mediated by myelin, could provide an important mechanism of activity
      dependent nervous system plasticity. Even small changes in CV, resulting from
      small changes in myelin thickness or nodal structure, could have profound effects
      on neuronal network function in terms of spike-time arrival, oscillation
      frequency, oscillator coupling, and propagation of brain waves. For example, a
      conduction delay of 5ms could change interactions of two coupled oscillators at
      the upper end of the gamma frequency range (~100Hz) from constructive to
      destructive interference; delays smaller than 1ms could change the phase by 30
      degrees , significantly affecting signal amplitude. Myelin plasticity, as another
      form of activity-dependent plasticity, is relevant not only to nervous system
      development but also to complex information processing tasks that involve
      coupling and synchrony among different brain rhythms. We use coupled oscillator
      models with time delays to explore the importance of adaptive time delays and
      adaptive synaptic strengths. The impairment of activity-dependent myelination and
      the loss of adaptive time delays may contribute to disorders where hyper- and
      hypo-synchrony of neuronal firing leads to dysfunction (e.g., dyslexia,
      schizophrenia, epilepsy). 

PMID- 24291732
TI  - Chronic mild stress-induced changes of risk assessment behaviors in mice are
      prevented by chronic treatment with fluoxetine but not diazepam.
AB  - As an important part of risk-related defensive behavior and central element of
      anxiety, risk assessment in rodents is particularly sensitive to psychosocial
      stress and may consequently influence the following decision-making and
      behavioral output. In this study, using a mouse-test battery, we evaluated the
      possible impacts of chronic mild stress (CMS) on risk assessment behaviors and
      action selections. For non-stressed control animals, a close relationship between
      risk assessment and choice behavior was observed in EPM and LDT. For stressed
      animals, however, 5 weeks of CMS exposure not only increased risk assessment
      behaviors, but also abolished the correlations between risk assessment and action
      selection. Pharmacological intervention with GABA-A receptor modulator diazepam
      (0.25-4 mg/kg) blocked the alterations of conventional spatiotemporal behaviors
      in response to CMS, but had no effect on the CMS-induced risk assessment
      behavioral changes. In contrast, 4-weeks of chronic treatment with fluoxetine (4
      20mg/kg), a selective serotonin reuptake inhibitor, not only ameliorated the CMS
      affected risk-assessment behaviors, but also restored the CMS-impaired
      correlations between risk assessment and decision making-related action
      selection. The present findings may shed new light on the better understanding of
      emotional reactivity and decision making under stressful situations. These
      results also indicate a differential pharmacological sensitivity in CMS-affected
      emotional response and risk-assessment behaviors.

PMID- 24291733
TI  - Cerebroprotective effects of ibuprofen on diabetic encephalopathy in rats.
AB  - OBJECTIVE: Diabetic encephalopathy is characterised by cognitive impairment,
      neurochemical and structural abnormalities. The aim of the study was to
      investigate the effects of ibuprofen on diabetic encephalopathy and potential
      mechanisms. RESEARCH DESIGN AND METHOD: Diabetes was induced through a single
      intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic rats were
      treated with ibuprofen (40 mg/kg) by gavage for 8 weeks. Cognitive performances
      were evaluated using Morris water maze. The temporal cortex and hippocampus were
      obtained to evaluate the levels of advanced glycation endproducts (AGEs) and
      their receptor (RAGE), the activity, protein expression, and mRNA levels of beta
      amyloid precursor protein cleaving enzyme 1 (BACE1), the protein and mRNA
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma), and
      the protein expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide
      synthase (iNOS). Blood was obtained for the evaluation of interleukin 1beta
      level. RESULTS: Chronic ibuprofen treatment significantly prevented the decline
      in learning and memory ability of diabetic rats and loss of neurons in the CA1
      and CA3 areas of the hippocampus. Moreover, ibuprofen treatment markedly reduced
      the activity, protein, and mRNA levels of BACE1, AGE level, protein expression of
      RAGE, COX-2, and iNOS in the brain, and interleukin 1beta level in serum, while
      increasing the protein and mRNA expression of PPARgamma in the brain of diabetic
      rats. However, ibuprofen had no effects on the hyperglycaemia and the body weight
      of diabetic rats. CONCLUSION: These findings demonstrated that ibuprofen markedly
      ameliorated diabetic encephalopathy, potentially reflecting the down-regulation
      of BACE1, the suppression of the AGE/RAGE axis, and the anti-inflammation in
      diabetic rat brain.

PMID- 24291734
TI  - Neuropathic pain in the general population: a systematic review of
      epidemiological studies.
AB  - Most patients with neuropathic pain symptoms present and are managed in primary
      care, with only a minority being referred for specialist clinical assessment and
      diagnoses. Previous reviews have focused mainly on specific neuropathic pain
      conditions based in specialist settings. This is the first systematic review of
      epidemiological studies of neuropathic pain in the general population. Electronic
      databases were searched from January 1966 to December 2012, and studies were
      included where the main focus was on neuropathic pain prevalence and/or
      incidence, either as part of a specific neuropathic pain-related condition or as
      a global entity in the general population. We excluded studies in which data were
      extracted from pain or other specialist clinics or focusing on specific
      population subgroups. Twenty-one articles were identified and underwent quality
      assessment and data extraction. Included studies differed in 3 main ways: method
      of data retrieval, case ascertainment tool used, and presentation of
      prevalence/incidence rates. This heterogeneity precluded any meta-analysis. We
      categorised comparable incidence and prevalence rates into 2 main subgroups: (1)
      chronic pain with neuropathic characteristics (range 3-17%), and (2) neuropathic
      pain associated with a specific condition, including postherpetic neuralgia (3.9
      42.0/100,000 person-years [PY]), trigeminal neuralgia (12.6-28.9/100,000 PY),
      painful diabetic peripheral neuropathy (15.3-72.3/100,000 PY), glossopharyngeal
      neuralgia (0.2-0.4/100,000 PY). These differences highlight the importance of a
      standardised approach for identifying neuropathic pain in future epidemiological
      studies. A best estimate of population prevalence of pain with neuropathic
      characteristics is likely to lie between 6.9% and 10%. 

PMID- 24291735
TI  - Fabrication of a high-performance hip prosthetic stem using beta Ti-33.6Nb-4Sn.
AB  - This study used severe cold rolling followed by cold swaging of beta Ti-33.6% Nb
      4% Sn rods to form a characteristic fiber structure composed of stress-induced
      alpha" martensite with <010> texture and a beta phase with <101> texture,
      resulting in a material with a low Young's modulus of 40GPa. The material's
      tensile strength of 1270MPa and fatigue strength of 850MPa were attained by heat
      treatment at 673K for 5h through fine alpha precipitation in the fiber structure.
      A new method of fabricating a high-performance hip prosthetic stem was
      investigated based on the low Young's modulus and high strength obtained. After
      fabricating the stem by cold rolling, cold swaging, cold die-forging and
      machining, its neck region was given higher strength through local heat
      treatment, while the low Young's modulus remained almost unchanged in a distal
      portion of the stem. When a stem tip in the distal part was heat treated at 423K,
      reverse alpha"->beta transformation occurred and the tangent modulus decreased to
      less than 30GPa, accompanied by stress-induced beta->alpha". It was concluded
      that the method presented herein provided a low Young's modulus of approximately
      40GPa in the distal part and high fatigue strength of approximately 850MPa in the
      neck region of a high-performance hip prosthetic stem.

PMID- 24291736
TI  - Zonation in the digestive tract of Eisenia fetida: implications in biomarker
      measurements for toxicity assessment.
AB  - Eisenia fetida is a model species for soil health assessment and different
      biomarkers that detect either the presence of bioavailable contaminants or their
      biological effect have been developed. These parameters are performed in a target
      tissue or whole earthworm, without considering the marked zonation in
      histological organisation, enzyme activities and gene expression pattern existing
      along the body. Thus, the present work was aimed at (a) characterising the
      morphofunctional heterogeneity along the digestive tract of E. fetida in tissue
      morphology and turnover, lysosomal enzyme markers (beta-glucuronidase, beta-GUS;
      hexosaminidase, HEX), lipofuscin contents (LPF) and metallothionein (MT) and
      catalase (CAT) gene expression; and (b) determining whether the responsiveness to
      Cd exposure varies among tissues and along the digestive tract. HEX and beta-GUS
      exhibited a heterogeneous distribution pattern along and across the digestive
      tract and Cd exposure caused a marked decrease of HEX and an increase of beta-GUS
      activity. Likewise, the significant decrease of cell turnover and the induction
      of MT transcription were was zone-dependent. Therefore, in was concluded that the
      consideration of the zonation when applying biomarker for toxicity assessment
      would reduce the intrinsic variability that results from overlooking the marked
      morphofunctional heterogeneity that exists in annelids along their body axis. 

PMID- 24291737
TI  - Handgrip strength and associated factors in hospitalized patients.
AB  - BACKGROUND: Handgrip strength (HGS) is a marker of nutrition status. Many factors
      are associated with HGS. Age, height, body mass index, number of diagnoses, and
      number and type of drugs have been shown to modify the association between
      undernutrition and HGS. Nevertheless, other patient characteristics that could
      modify this association and its joint modifier effect have not been studied yet.
      OBJECTIVE: To evaluate the association of inpatients' HGS and undernutrition
      considering the potential modifier effect of cognitive status, functional
      activity, disease severity, anthropometrics, and other patient characteristics on
      HGS. METHODS: A cross-sectional study was conducted in a university hospital.
      Sex, age, abbreviated mental test score, functional activity score, Charlson
      index, number of drugs, Patient-Generated Subjective Global Assessment (PG-SGA)
      score, body weight, mid-arm muscle circumference, adductor pollicis muscle
      thickness, body height, wrist circumference, hand length, and palm width were
      included in a linear regression model to identify independent factors associated
      with HGS (dependent variable). RESULTS: The study sample was composed of 688
      inpatients (18-91 years old). All variables included in the model were associated
      with HGS (beta, -0.16 to 0.38; P <= .049) and explained 68.5% of HGS. Age,
      functional activity decline, Charlson index, number of drugs, PG-SGA score, body
      weight, and wrist circumference had a negative association with HGS. All other
      studied variables were positively associated with HGS. CONCLUSION: Nutrition
      status evaluated by PG-SGA was still associated with HGS after considering the
      joint effect of other patient characteristics, which reinforces the value of HGS
      as an indicator of undernutrition.

PMID- 24291738
TI  - Normalizing glutamine concentration causes mitochondrial uncoupling in an in
      vitro model of human skeletal muscle.
AB  - BACKGROUND: Glutamine has been considered essential for rapidly dividing cells,
      but its effect on mitochondrial function is unknown. MATERIALS AND METHODS: Human
      myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed
      for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and
      5000 uM). Cells were trypsinized and manually counted every 5 days. Seven days
      before the end of exposure, half of these cells were allowed to differentiate to
      myotubes. Afterward, energy metabolism in both myotubes and myoblasts was
      assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA).
      The protocol for myoblasts was optimized in preliminary experiments. To account
      for different mitochondrial density or cell count, data were normalized to
      citrate synthase activity. RESULTS: Fastest myoblast proliferation was observed
      at 300 uM glutamine, with a significant reduction at 0 and 100 uM. Glutamine did
      not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain
      capacity. Glutamine significantly (P = .015) influenced the leak through the
      inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200
      300 uM glutamine (~90% of oxygen used for adenosine triphosphate synthesis).
      Increased glutamine concentration to 500 or 5000 uM caused mitochondrial
      uncoupling in myoblasts and myotubes, decreasing the efficiency of the
      respiratory chain to ~70%. CONCLUSION: Glutamine concentrations, consistent with
      moderate clinical hypoglutaminemia (300 uM), bring about an optimal condition of
      myoblast proliferation and for efficiency of aerobic phosphorylation in an in
      vitro model of human skeletal muscle. These data support the hypothesis of
      hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic
      failure (eg, critical illness).

PMID- 24291739
TI  - Characterization and evaluation of the immune responses elicited by a novel human
      papillomavirus (HPV) therapeutic vaccine: HPV 16E7-HBcAg-Hsp65 fusion protein.
AB  - Human papillomaviruses (HPV), particularly HPV16, are associated with most
      cervical cancers. Currently, although prophylactic vaccines have been developed,
      there is still an urgent need to develop therapeutic HPV vaccines. In this study,
      a novel fusion protein, HPV 16 E7-HBcAg-Hsp65 (VR111), with the goal of
      increasing anti-HPV16 cellular immunity was developed. VR111 was analyzed using
      SDS-PAGE, western-blotting, capillary isoelectric focusing (cIEF), analytical
      ultracentrifugation (AUC) and dynamic light scattering (DLS). Gamma interferon
      (IFN-gamma) secretion assay was performed by enzyme-linked immunospot (ELISPOT)
      and ELISA to test their ability to induce cellular immune response. Significant
      correlation between ELISPOT and ELISA was observed (r=0.8680, p<0.0001). It was
      shown that VR111 could induce a significant increase in E7-specific CD8(+) T cell
      responses. Humoral immune response was also observed. The antibody titer levels
      were measured by ELISA. These results indicated that VR111 was a promising
      therapeutic vaccine for treatment of cervical cancer with possible therapeutic
      potential in clinical settings. 

PMID- 24291740
TI  - The development of a loop-mediated isothermal amplification assay for rapid and
      sensitive detection of abalone herpesvirus DNA.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed for the
      detection of abalone herpesvirus DNA. Two pairs of primers were designed, based
      on the sequence of the DNA polymerase gene of abalone herpesvirus. The reaction
      temperature and time were optimized to 63 degrees C and 60min, respectively. LAMP
      amplicons were analyzed by 2% agarose gel electrophoresis or by visual inspection
      of a colour change emitted by fluorescent dye. The method developed was specific
      for the detection of abalone herpesvirus, without cross-reactions with other
      tested herpesviruses including ostreid herpesvirus 1 (OsHV-1), European eel
      herpesvirus, koi herpesvirus (KHV) and an avian herpesvirus. The LAMP assay was
      100 folds more sensitive than a conventional PCR and 10 folds less sensitive than
      a SYBR Green PCR. These results indicate that the developed LAMP assay is a
      simple, rapid, sensitive, specific and reliable technique for the detection of
      abalone herpesvirus. 

PMID- 24291741
TI  - Doxorubicin has in vivo toxicological effects on ex vivo cultured mesenchymal
      stem cells.
AB  - Doxorubicin (dox) is an effective chemotherapeutic agent that leads to
      cardiotoxicity. An alternative treatment for dox-cardiotoxicity is autologous
      mesenchymal stem cells (MSCs) transplantation. It remains unclear if dox has
      deleterious effects on MSCs from subjects under chemotherapy, therefore this
      study aimed to evaluate dox in vivo toxicological effects on ex vivo cultured
      MSCs, inferring whether autologous transplantation may be an alternative
      treatment in patients who are exposed to the drug. Wistar rats received either
      dox or saline. Following treatments, animals were sacrificed and bone marrow MSCs
      were isolated, characterized for cell surface markers and assessed according to
      their viability, alkaline phosphatase production, and proliferation kinetics.
      Moreover, MSCs were primed to cardiac differentiation and troponin T and connexin
      43 expressions were evaluated. Compared to control, undifferentiated MSCs from
      dox group kept the pattern for surface marker and had similar viability results.
      In contrast, they showed lower alkaline phosphatase production, proliferation
      rate, and connexin 43 expression. Primed MSCs from dox group showed lower
      troponin T levels. It was demonstrated a toxic effect of dox in host MSCs. This
      result renders the possibility of autologous MSCs transplantation to treat dox
      cardiotoxicity, which could be a non-suitable option for subjects receiving such
      antineoplastic agent. 

PMID- 24291742
TI  - Epigenetic histone modification regulates developmental lead exposure induced
      hyperactivity in rats.
AB  - Lead (Pb) exposure was commonly considered as a high environmental risk factor
      for the development of attention-deficit/hyperactivity disorder (ADHD). However,
      the molecular basis of this pathological process still remains elusive. In light
      of the role of epigenetics in modulating the neurological disease and the
      causative environment, the alterations of histone modifications in the
      hippocampus of rats exposed by various doses of lead, along with concomitant
      behavioral deficits, were investigated in this study. According to the free and
      forced open field test, there showed that in a dosage-dependent manner, lead
      exposure could result in the increased locomotor activity of rats, that is,
      hyperactivity: a subtype of ADHD. Western blotting assays revealed that the
      levels of histone acetylation increased significantly in the hippocampus by
      chronic lead exposure, while no dramatic changes were detected in terms of
      expression yields of ADHD-related dopaminergic proteins, indicating that histone
      acetylation plays essential roles in this toxicant-involved pathogenesis. In
      addition, the increased level of histone acetylation might be attributed to the
      enzymatic activity of p300, a typical histone acetyltransferase, as the
      transcriptional level of p300 was significantly increased upon higher-dose Pb
      exposure. In summary, this study first discovered the epigenetic mechanism
      bridging the environmental influence (Pb) and the disease itself (ADHD) in the
      histone modification level, paving the way for the comprehensive understanding of
      ADHD's etiology and in further steps, establishing the therapy strategy of this
      widespread neurological disorder. 

PMID- 24291743
TI  - Uremic toxin indoxyl 3-sulfate regulates the differentiation of Th2 but not of
      Th1 cells to lessen allergic asthma.
AB  - Immune system dysfunctions including the increased Th1/Th2 ratio are common in
      chronic kidney disease (CKD) patients, and a wide variety of skin diseases
      including Th1-mediated uremic pruritis are associated with CKD. Although there
      are more than 90 uremic toxins reported, it is yet to be known which uremic
      solute is associated with the unbalanced Th1/Th2 ratio and how it works. Indoxyl
      3-sulfate (I3S), one of uremic toxins and a potent aryl hydrocarbon receptor
      (AhR) ligand, accumulates in blood and tissues, increasing up to 81.04 MUM in CKD
      patients, compared with 1.03 MUM in healthy subjects. I3S activates NF-kappaB and
      AhR. Thus, we investigated roles of I3S in the differentiation of Th1 and Th2
      cells. I3S inhibited Th2 differentiation but showed little or no effect on Th1
      differentiation. I3S suppressed Th2-mediated ovalbumin-induced allergic asthma in
      mice and decreased the frequency of IL-4 producing CD4 T cells in the lungs. I3S
      inhibited phosphorylation of STAT5 and STAT6, transcription factors associated
      with Th2 differentiation. Effects of I3S on Th2 differentiation were suppressed
      by alpha-naphtoflavone, an AhR antagonist, indicating that I3S regulates Th2
      differentiation AhR-dependently.

PMID- 24291745
TI  - Expression and cell distribution of receptor for advanced glycation end-products
      in the rat cortex following experimental subarachnoid hemorrhage.
AB  - Convincing evidence indicates that inflammation contributes to the adverse
      prognosis of subarachnoid hemorrhage (SAH). Some pro-inflammatory molecules such
      as high mobility group protein 1, S100 family of proteins, beta-amyloid peptide,
      and macrophage antigen complex 1 have been involved in the damaging inflammation
      process following SAH. The receptor for advanced glycation end-products (RAGE) is
      a transmembrane receptor that senses these molecules and plays central role in
      inflammatory processes. This study aimed to determine the expression and cell
      distribution of RAGE in the brain cortex after SAH. Male Sprague-Dawley rats were
      randomly divided into sham group and SAH groups at 6 h, 12 h and on day 1, day 2
      and day 3 (n=6 for each subgroup). SAH groups suffered experimental SAH by
      injection of 0.3 ml autologous blood into the prechiasmatic cistern. RAGE
      expression was measured by Western blot, real-time PCR, immunohistochemistry and
      immunofluorescence. Nuclear expression of p65 protein, the major subunit of
      nuclear factor kappa B, was also detected. Our data demonstrated that the
      expression levels of RAGE and nuclear p65 protein were both markedly increased
      after SAH. Moreover, there was a significant positive correlation between the
      expression of RAGE and that of p65 protein. Double immunofluorescence staining
      showed that RAGE was expressed by neuron and microglia rather than astrocyte
      after SAH. These results suggest that RAGE may be directly involved in the
      inflammatory response after SAH, and there might be important implications for
      further studies using specific RAGE antagonists to decrease inflammation-mediated
      brain injury following SAH.

PMID- 24291746
TI  - CXCR5+CD4+ follicular helper T cells accumulate in resting human lymph nodes and
      have superior B cell helper activity.
AB  - Although many relevant immune reactions are initiated in the lymph nodes, this
      compartment has not been systematically studied in humans. Analyses have been
      performed on immune cells derived from tonsils, but as this tissue is most often
      inflamed, generalization of these data is difficult. Here, we analyzed the
      phenotype and function of the human CD4(+) T-cell subsets and lineages in paired
      resting lymph node and peripheral blood samples. Naive, central memory cells and
      effector memory cells as well as Th1, Th2, Th17 and Treg cells were equally
      represented in both compartments. On the other hand, cytotoxic CD4(+) T cells
      were strikingly absent in the lymph nodes. CXCR5(+)CD4(+) T cells, representing
      putative follicular Th (Tfh) cells were over-represented in lymph nodes and
      expressed higher levels of Tfh markers than their peripheral blood counterparts.
      Compared with the circulating pool, lymph-node-derived CXCR5(+)CD4(+) T cells
      were superior in providing help to B cells. Thus, functionally competent Tfh
      cells accumulate in resting human lymph nodes, providing a swift induction of
      naive and memory antibody responses upon antigenic challenge. 

PMID- 24291744
TI  - Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae
      impairs development of the motor pattern.
AB  - Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel
      and kinase implicated in the differentiation or function of many cell types.
      Early lethality in mice and frogs depleted of the corresponding gene impedes
      investigation of the functions of this protein particularly during later stages
      of development. By contrast, zebrafish trpm7 mutant larvae undergo early
      morphogenesis normally and thus do not have this limitation. The mutant larvae
      are characterized by multiple defects including melanocyte cell death, transient
      paralysis, and an ion imbalance that leads to the development of kidney stones.
      Here we report a requirement for Trpm7 in differentiation or function of
      dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail
      to make a dopamine-dependent developmental transition in swim-bout length. Both
      of these deficits are partially rescued by the application of levodopa or
      dopamine. Second, histological analysis reveals that in trpm7 mutants a
      significant fraction of dopaminergic neurons lack expression of tyrosine
      hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants
      are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an
      oxidative stressor, and their motility is partially rescued by application of the
      iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which
      model aspects of human dopaminergic neurons, forced expression of a channel-dead
      variant of TRPM7 causes cell death. In summary, a forward genetic screen in
      zebrafish has revealed that both melanocytes and dopaminergic neurons depend on
      the ion channel Trpm7. The mechanistic underpinning of this dependence requires
      further investigation. 

PMID- 24291747
TI  - Purification and characterization of a carboxymethyl cellulase from Artemia
      salina.
AB  - Brine shrimp (Artemia salina) belong to a group of crustaceans that feed on
      microalgae and require a cellulase enzyme that can be used in ethanol production
      from marine algae. Protein with potential cellulase activity was purified and the
      activity analyzed under different conditions. After initial identification of
      cellulase activity by CMC cellulase, surface sterilization and PCR using 16s rRNA
      primers was conducted to confirm that the cellulase activity was not produced
      from contaminating bacteria. The enzyme was purified by ammonium sulfate
      fractionation, gel filtration, and ion exchange chromatography. After the final
      purification, a 70-fold increase in specific enzyme activity was observed. SDS
      PAGE results revealed that the cellulase enzyme had a molecular mass of 96 kDa.
      Temperature, pH, and salinity values were found to be optimal at 55  degrees C,
      pH 8.0, and 600 mM NaCl, respectively. Specifically, the enzyme showed a fivefold
      increase in enzyme activity in seawater compared to 600 mM NaCl in phosphate
      buffer. Further analysis of the purified enzyme by molecular spectrometry showed
      no match to known cellulases, indicating this enzyme could be a novel halophilic
      cellulase that can be used for the production of bioethanol from marine
      macroalgae.

PMID- 24291748
TI  - Smoking ban policies and their influence on smoking behaviors among current
      California smokers: a population-based study.
AB  - OBJECTIVE: To assess whether smoking ban policies are associated with smoking
      reduction and quit attempts among California smokers. METHODS: Data were examined
      for 1718 current smokers from follow-up telephone interviews conducted in 2011 of
      persons previously identified as smokers in a representative sample of the adult
      population of California. Population weighted logistic regressions controlling
      for demographic and other variables were used to evaluate the association between
      smoking ban policies (home, work, and town) and changes in tobacco use (past year
      quit attempt or reduction in smoking rate). RESULTS: Living in a home with a
      total ban was significantly associated with smoking reduction (adjusted odds
      ratio, AOR: 2.4, 95% CI: 1.4-4.2) and making a quit attempt (AOR: 2.3, 95% CI:
      1.3-3.9) compared to living in a home with no home ban. Self-reported perception
      of an outdoor ban in one's city/town was associated with smoking reduction (AOR:
      1.7, 95% CI: 1.02-2.7) and making a quit attempt (AOR: 1.8, 95% CI: 1.05-2.9).
      CONCLUSION: These results indicate that smoking bans not only protect nonsmokers
      from the harms of secondhand smoke, but are also associated with smoking
      reduction and cessation.

PMID- 24291749
TI  - Re: questionable evidence of effectiveness of a national cardiovascular disease
      risk assessment program.

PMID- 24291750
TI  - Femtomole level photoelectrochemical aptasensing for mercury ions using quercetin
      copper(II) complex as the DNA intercalator.
AB  - An ultrasensitive and selective photoelectrochemical (PEC) aptasensor for mercury
      ions was first fabricated based on perylene-3, 4, 9, 10-tetracarboxylic
      acid/graphene oxide (PTCA/GO) heterojunction using quercetin-copper(II) complex
      intercalated into the poly(dT)-poly(dA) duplexes. Both the PTCA/GO heterojunction
      and the quercetin-copper(II) complex are in favor of the sensitivity for the
      fabricated PEC aptasensor due to band alignment and strong reduction capability,
      respectively. And they efficiently promote the separation of photoexcited
      carriers and enhance the photocurrent. The formation of thymine-Hg(2+)-thymine
      coordination chemistry resulted in the dehybridization of poly(dT)-poly(dA)
      duplexes and then the intercalator quercetin-copper(II) complex broke away from
      the surface of the PEC aptasensor. As the concentration of mercury ions
      increased, the photocurrent gradually decreased. The electrode response for
      mercury ions detection was in the linear range from 0.01 pmol L(-1) to 1.00 pmol
      L(-1) with the detection limit of 3.33 fmol L(-1). The label-free PEC aptasensor
      has excellent performances with ultrasensitivity and good selectivity besides the
      advantage of economic and facile fabrication. The strategy of quercetin
      copper(II) complex as a novel DNA intercalator paves a new way to improve the
      performances for PEC sensors.

PMID- 24291751
TI  - Layer-by-layer multienzyme assembly for highly sensitive electrochemical
      immunoassay based on tyramine signal amplification strategy.
AB  - A new sandwich-type electrochemical immunosensor based on nanosilver-doped bovine
      serum albumin microspheres (Ag@BSA) with a high ratio of horseradish peroxidase
      (HRP) and detection antibody was developed for quantitative monitoring of
      biomarkers (carcinoembryonic antigen, CEA, used in this case) by coupling
      enzymatic biocatalytic precipitation with tyramine signal amplification strategy
      on capture antibody-modified glassy carbon electrode. Two immunosensing protocols
      (with and without tyramine signal amplification) were also investigated for the
      detection of CEA and improved analytical features were acquired with tyramine
      signal amplification strategy. With the labeling method, the performance and
      factors influencing the electrochemical immunoassay were studied and evaluated in
      detail. Under the optimal conditions, the electrochemical immunosensor exhibited
      a wide dynamic range of 0.005-80 ng mL(-1) toward CEA standards with a low
      detection limit of 5.0 pg mL(-1). Intra- and inter-assay coefficients of
      variation were below 11%. No significant differences at the 0.05 significance
      level were encountered in the analysis of 6 clinical serum specimens and 6 spiked
      new-born cattle serum samples between the electrochemical immunoassay and the
      commercialized electrochemiluminescent immunoassay method for the detection of
      CEA.

PMID- 24291752
TI  - Quantum dots sensitized titanium dioxide decorated reduced graphene oxide for
      visible light excited photoelectrochemical biosensing at a low potential.
AB  - A low potential and competitive photoelectrochemical biosensing platform was
      developed using quantum dots sensitized titanium dioxide decorated reduced
      graphene oxide (TiO2-RGO) nanocomposites. The nanocomposites were prepared
      through electrostatic interaction between mercaptoacetic acid wrapped CdSe
      quantum dots with negative charge and TiO2-RGO hybrids with positive charge
      obtained via ultrasonic and acid treatments. Electron microscopes and
      spectroscopes were used to characterize the functionalized nanocomposites films
      of CdSe/TiO2-RGO, and the fabrication process of the photoelectrochemical
      biosensor. Based on the high photovoltaic conversion efficiency of CdSe/TiO2-RGO
      nanocomposites films, after introducing biological recognition and competitive
      immunoreaction, a low potential and competitive photoelectrochemical biosensor
      for carcinoembryonic antigen (CEA) detection was fabricated. The synergic effect
      of horseradish peroxide and benzo-4-chlorohexadienone decreased the background
      signal, leading to signal amplification. Under the light irradiation of 430 nm
      and the applied potential of 0 V, the biosensor detected CEA with a linear range
      from 0.003 to 100 ng mL(-1) and the detection limit was estimated to be 1.38 pg
      mL(-1) at a S/N of 3. It was satisfactory for clinical sample detection. The
      proposed competitive and low potential photoelectrochemical biosensor under
      irradiation of visible light exhibited good performance, which has a promising
      prospect in clinical diagnose.

PMID- 24291753
TI  - In-situ and label-free optical monitoring of the adhesion and spreading of
      primary monocytes isolated from human blood: dependence on serum concentration
      levels.
AB  - Adhesion and spreading of primary monocytes isolated from human blood were
      monitored utilizing optical waveguide lightmode spectroscopy (OWLS); a highly
      sensitive label-free biosensor technique using evanescent optical waves generated
      at a biocompatible surface. Appropriate development on a custom built setup
      enabled the OWLS cuvette to be operated as a 1.5 ml mini-incubator, controlling
      both temperature and CO2 levels. The incubator-equipped OWLS is readily
      applicable for delicate and long-term studies on sensitive primary cells,
      demonstrated here through monitoring the serum dependence of the adhesion and
      spreading of human monocytes. Moreover, the custom-built setup enables the
      simultaneous monitoring of the position and overall width of the OWLS resonant
      peaks. This unique feature makes it possible to distinguish the refractive index
      variations induced by the adsorption of secreted material from refractive index
      changes provoked by cellular spreading. A definite attachment and spreading
      activity was observed on the substratum (glassy silica-titania), when the serum
      level of the culturing medium was 0.0-0.01%. Increasing serum concentration
      resulted in a steep fall in monocyte surface adhesion and spreading. 1.0% serum
      level practically abolished all spreading activity measured by OWLS, and the
      number of attached cells was significantly decreased, too. Serum addition to
      fully spread cells provoked a reduction in the cell-substratum contact area,
      clearly detectable by the biosensor. Cell spreading was inhibited by pre-coating
      the sensor surface with considerable amounts of serum proteins. These findings
      suggest that monocyte spreading is inhibited by the adsorption of serum
      biomolecules to the substratum, rather than by soluble factors present in the
      serum. All of these results were obtained completely noninvasively with real time
      monitoring; demonstrating the capabilities of OWLS to sensitively monitor the
      adhesion properties of immune cells isolated from human blood. The current study
      is, therefore, a significant step towards the application of label-free optical
      biosensors in medical diagnostics.

PMID- 24291754
TI  - Growth phenotype screening of Schizosaccharomyces pombe using a Lensless
      microscope.
AB  - The Lensless microscope has a large field of view and allows the capture of the
      diffraction pattern from a large number of cells simultaneously. A simple
      algorithm to measure intensity changes in the Airy Disc First Fringe (ADFF) has
      been derived to follow the growth characteristics of the unicellular yeast
      Schizosaccharomyces pombe. The performance of the algorithm is calibrated using
      comparison between optical image and ADFF analysis of polystyrene microspheres
      with known dimensions and has an accuracy of 5% over all lengths above the
      diffraction-limited measurements. We have observed the growth characteristics of
      S. pombe for N=100 cells to determine the growth phenotype distributions of
      Length (L(t=0)) and width (W(t=0)) on arrival at the surface, lag phase
      adjustment to the new growth conditions (B), the length at birth, LB, and cell
      cycle length, tcell. The observed cell width distribution has a median width of
      3.9 (+/-0.1) um, as expected, but a non-normal distribution. Similarly, all
      growth parameters studied, L(t=0), LB and cell cycle time are phenotypes with non
      normal distributions but with medians consistent with the literature values.

PMID- 24291755
TI  - Jatrophane diterpenoid esters from Euphorbia sororia serving as multidrug
      resistance reversal agents.
AB  - Six (1-6) new jatrophane diterpenoid esters together with four known compounds (7
      10) were isolated from the acetone extract of fructus Euphorbia sororia. Their
      structures were elucidated by the spectral technology, including the 2D NMR
      experiments (HMQC, HMBC and NOESY). The absolute configuration of compound 1 and
      compound 7 were first confirmed by X-ray crystallographic analysis. Compounds 1-7
      were assayed for their antiproliferative activity in human cancer cell lines:
      human mammary adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549). All
      the compounds were inactive for the cell lines. The multidrug-resistance reversal
      activity was also tested on KBv200 cells and compound 2 displayed strong
      multidrug resistance reversal activity, outperforming verapamil at 10 MUM.

PMID- 24291756
TI  - Hypocholesterolaemic and antioxidant effects of yerba mate (Ilex paraguariensis)
      in high-cholesterol fed rats.
AB  - OBJECTIVE: To study the effect of mate (Ilex paraguariensis) on serum lipids and
      antioxidant status in normocholesterolaemic and hypercholesterolaemic rats.
      METHODS: Triglycerides (TG), total, LDL- and HDL-cholesterol levels, total
      antioxidant capacity (FRAP and ABTS assays), malondialdehyde (MDA) and protein
      carbonyls were analysed in serum, and MDA, glutathione and antioxidant enzyme
      activity in livers of rats drinking water or mate fed normal or cholesterol
      cholic supplemented diets. RESULTS: ABTS, glutathione and antioxidant enzymes
      were not affected by any treatment. In normocholesterolaemic animals, mate had no
      effect on serum lipids or antioxidant status, yet it increased serum carbonyls
      and liver MDA concentrations. In hypercholesterolaemic rats, mate consumption had
      no effect on HDL-cholesterol or protein carbonyls, yet it showed a marked
      hypolipidaemic action, decreasing TG, total and LDL-cholesterol, and serum MDA
      levels that had been increased after consuming the high-cholesterol diet.
      CONCLUSION: Potential beneficial effect of mate on markers of cardiovascular risk
      seems to be restricted to hyperlipaemic animals.

PMID- 24291757
TI  - Inhibition of human organic cation transporters by the alkaloids matrine and
      oxymatrine.
AB  - Human organic cation transporters (hOCTs; SLC22) are expressed in many organs,
      including intestine, liver, kidney, heart and brain, where they contribute to the
      absorption, distribution, and elimination of endogenous and exogenous substances.
      The alkaloids matrine and oxymatrine are widely used in herbal medicine for the
      treatment of cancer, as well as viral, and cardiac diseases. Their
      physicochemical properties indicated that they are potential inhibitors for
      hOCTs, leading to drug-drug interactions in vivo. Therefore, we assessed the
      inhibitory effects of matrine and oxymatrine on the function of hOCT1 (SLC22A1),
      hOCT2 (SLC22A2) and hOCT3 (SLC22A3) using stably transfected transporter
      expressing cells. At 100-fold excess, oxymatrine exhibited marked inhibition of
      hOCT1-mediated substrate uptake (p<0.05), while matrine failed to produce
      significant inhibition on hOCT1. The IC50 value for oxymatrine on hOCT1 was
      estimated as 513+/-132 MUM. While there was no significant inhibition of hOCT2 or
      hOCT3 at 100-fold excess, oxymatrine and matrine showed 42% and 88% inhibition of
      hOCT3-mediated substrate uptake at 3 and 6mM, respectively. Considering the
      potential intestinal lumen and reported plasma concentrations of matrine and
      oxymatrine, these data suggest that drug-drug interactions may occur during hOCT1
      mediated hepatic and renal uptake and during hOCT3-mediated intestinal
      absorption.

PMID- 24291758
TI  - Influences of the substrate feeding regime on methanogenic activity in biogas
      reactors approached by molecular and stable isotope methods.
AB  - In order to better understand the effects of the substrate feeding regime on
      methanogenesis during anaerobic digestion in biogas reactors, four continuous
      stirred tank reactors operated under mesophilic conditions were investigated. In
      addition to standard physicochemical parameters, the stable isotopic signatures
      of CH4 and CO2 before and after daily feeding were analyzed. The activity of the
      methanogens was assessed by methyl coenzyme M reductase alpha-subunit (mcrA/mrtA)
      gene transcript analysis. Two different feeding regimes i.e. single vs. double
      consecutive feeding of the otherwise same daily maize silage load were
      investigated. During the first phase, a single feeding of the whole daily dose
      increased the biogas production within 70-80 min from around 0.5 to 2.0 L/h. This
      increase was associated with a transient increase of the acetic acid
      concentration and a corresponding decrease of the pH. Only moderate increase in
      biogas yield and VFA concentration (mainly acetate) was observed when the daily
      substrate was apportioned into two feedings. However, the overall daily gas
      production was similar in both cases. Regardless of the feeding regime,
      significantly depleted delta(13)CH4 and minor changes in the CO2 content of
      biogas were observed after feeding, which were followed by enrichment of
      delta(13)CH4. This period was associated with detectable changes in activity of
      methanogenic communities monitored by terminal restriction fragment length
      polymorphism analysis based on the transcripts of mcrA/mrtA genes. Methanoculleus
      and Methanobacterium spp. were the predominant methanogens in all reactors, while
      Methanosarcina spp. activity was only significant in two reactors. The activity
      of Methanoculleus and Methanosarcina spp. increased after the feeding in these
      reactors, which was followed by a depletion of delta(13)C in the produced gas. In
      both reactors, the less depleted isotopic values were detected before the second
      feeding, when Methanobacterium was the most active genus. Variations in reactor
      performance and methanogenic community characteristics were attributed to
      inoculum heterogeneity and stochastic factors during the reactor set up. 

PMID- 24291759
TI  - In vitro evaluation of the safety and probiotic properties of Lactobacilli
      isolated from chicken and calves.
AB  - A total of 73 chicken and calves isolates were diagnosed using matrix-assisted
      laser desorption ionization-time-of flight mass spectrometry (Maldi-Tof MS).
      After a preliminary subtractive screening based on the high acid tolerance at pH
      2.5 and bile resistance at 0.3% oxgall, twenty isolates belonging to the species
      Lactobacillus salivarius, Lactobacillus agilis, Lactobacillus reuteri,
      Lactobacillus murinus and Lactobacillus amylovorus were in vitro screened for the
      safety assessment and probiotic properties, including antibiotics susceptibility
      patterns, biochemical activity and potential for competitive exclusion of biofilm
      producing pathogens determined by crystal violet and/or quantitative Fluorescent
      in situ Hybridisation (FISH) assays utilizing 5'Cy 3 labelled probe Enter1432 for
      enteric group. Antibiotic susceptibility testing was performed according to the
      ISO norm 10932. The sixteen strains were susceptible to certain antimicrobial
      agents, except for two chicken (L. salivarius 12K, L. agilis 13K) and two calves
      (L. reuteri L10/1, L. murinus L9) isolates with the presence non wild-type ECOFFs
      (epidemiological cut-off) for gentamicin (>=256 MUg ml(-1)), tetracycline (>=128
      MUg ml(-1)), kanamycin (>=256 MUg ml(-1)) and streptomycin (>=96 MUg ml(-1)). The
      two referenced chicken isolates gave positive aac(6')Ie-aph(2")Ia and tet(L) PCR
      results. The wild-type ECOFFs isolates were subjected to the apiZYM analysis for
      enzyme profile evaluation and amino acid decarboxylase activities determined by
      qualitative plate method and multiplex PCR for the detection of four genes
      involved in the production of histamine (histidine decarboxylase, hdc), tyramine
      (tyrosine decarboxylase, tyrdc) and putrescine (via eithers ornithine
      decarboxylase, odc, or agmatine deiminase, agdi). From examined strains only two
      chicken isolates (L. reuteri 14K; L. salivarius 15K) had no harmful beta
      glucuronidase, beta-glucosidase activities connected with detrimental effects in
      the gastrointestinal tract and together no amino acid decarboxylase activities
      and no genes associated with biogenic amines production though only chicken L.
      salivarius 15K whole cells and acid supernatants shown strong suppressive
      potential against biofilm-forming Klebsiella and Escherichia coli. Our results
      highlight that above-mentioned isolate L. salivarius 15K fulfils the principle
      requirements of a qualified probiotic and may be seen as a reliable candidate for
      further validation studies in chicken. 

PMID- 24291760
TI  - Luminal epithelium in endometrial fragments affects their vascularization, growth
      and morphological development into endometriosis-like lesions in mice.
AB  - In endometriosis research, endometriosis-like lesions are usually induced in
      rodents by transplantation of isolated endometrial tissue fragments to ectopic
      sites. In the present study, we investigated whether this approach is affected by
      the cellular composition of the grafts. For this purpose, endometrial tissue
      fragments covered with luminal epithelium (LE(+)) and without luminal epithelium
      (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive
      (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type
      recipient animals to analyze their vascularization, growth and morphology by
      means of repetitive intravital fluorescence microscopy, histology and
      immunohistochemistry during a 14-day observation period. LE(-) fragments
      developed into typical endometriosis-like lesions with cyst-like dilated
      endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+)
      fragments exhibited a polypoid morphology and a significantly reduced blood
      perfusion after engraftment, because the luminal epithelium prevented the
      vascular interconnection with the microvasculature of the surrounding host
      tissue. This was associated with a markedly decreased growth rate of LE(+)
      lesions compared with LE(-) lesions. In addition, we found that many GFP(+)
      microvessels grew outside the LE(-) lesions and developed interconnections to the
      host microvasculature, indicating that inosculation is an important mechanism in
      the vascularization process of endometriosis-like lesions. Our findings
      demonstrate that the luminal epithelium crucially affects the vascularization,
      growth and morphology of endometriosis-like lesions. Therefore, it is of major
      importance to standardize the cellular composition of endometrial grafts in order
      to increase the validity and reliability of pre-clinical rodent studies in
      endometriosis research. 

PMID- 24291761
TI  - Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in
      vitro.
AB  - Homeostasis of mammalian cell function strictly depends on balancing oxygen
      exposure to maintain energy metabolism without producing excessive reactive
      oxygen species. In vivo, cells in different tissues are exposed to a wide range
      of oxygen concentrations, and yet in vitro models almost exclusively expose
      cultured cells to higher, atmospheric oxygen levels. Existing models of liver
      stage malaria that utilize primary human hepatocytes typically exhibit low in
      vitro infection efficiencies, possibly due to missing microenvironmental support
      signals. One cue that could influence the infection capacity of cultured human
      hepatocytes is the dissolved oxygen concentration. We developed a microscale
      human liver platform comprised of precisely patterned primary human hepatocytes
      and nonparenchymal cells to model liver-stage malaria, but the oxygen
      concentrations are typically higher in the in vitro liver platform than anywhere
      along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium
      parasite development in vivo correlates with hepatic sinusoidal oxygen gradients.
      Therefore, we hypothesized that in vitro liver-stage malaria infection
      efficiencies might improve under hypoxia. Using the infection of micropatterned
      co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum
      as a model, we observed that ambient hypoxia resulted in increased survival of
      exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in
      a subset of surviving EEFs, based on EEF size. Further, the effective cell
      surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a
      mathematical model, were systematically perturbed by varying culture parameters
      such as hepatocyte density and height of the medium, uncovering an optimal cell
      surface pO2 to maximize the number of mature EEFs. Initial mechanistic
      experiments revealed that treatment of primary human hepatocytes with the hypoxia
      mimetic, cobalt(II) chloride, as well as a HIF-1alpha activator,
      dimethyloxalylglycine, also enhance P. berghei infection, suggesting that the
      effect of hypoxia on infection is mediated in part by host-dependent HIF-1alpha
      mechanisms. 

PMID- 24291762
TI  - Inhibitors of neutrophil recruitment identified using transgenic zebrafish to
      screen a natural product library.
AB  - Cell migration is fundamental to the inflammatory response, but uncontrolled cell
      migration and excess recruitment of neutrophils and other leukocytes can cause
      damage to the tissue. Here we describe the use of an in vivo model - the
      Tg(mpx:GFP)(i114) zebrafish line, in which neutrophils are labelled by green
      fluorescent protein (GFP) - to screen a natural product library for compounds
      that can affect neutrophil migratory behaviour. Among 1040 fungal extracts
      screened, two were found to inhibit neutrophil migration completely.
      Subfractionation of these extracts identified sterigmatocystin and antibiotic
      PF1052 as the active components. Using the EZ-TAXIScan chemotaxis assay, both
      compounds were also found to have a dosage-dependent inhibitory effect on murine
      neutrophil migration. Furthermore, neutrophils treated with PF1052 failed to form
      pseudopods and appeared round in shape, suggesting a defect in PI3-kinase (PI3K)
      signalling. We generated a transgenic neutrophil-specific PtdIns(3,4,5)P3 (PIP3)
      reporter zebrafish line, which revealed that PF1052 does not affect the
      activation of PI3K at the plasma membrane. In human neutrophils, PF1052 neither
      induced apoptosis nor blocked AKT phosphorylation. In conclusion, we have
      identified an antibiotic from a natural product library with potent anti
      inflammatory properties, and have established the utility of the mpx:GFP
      transgenic zebrafish for high-throughput in vivo screens for novel inhibitors of
      neutrophil migration. 

PMID- 24291764
TI  - Rainfall-induced fecal indicator organisms transport from manured fields: model
      sensitivity analysis.
AB  - Microbial quality of surface waters attracts attention due to food- and
      waterborne disease outbreaks. Fecal indicator organisms (FIOs) are commonly used
      for the microbial pollution level evaluation. Models predicting the fate and
      transport of FIOs are required to design and evaluate best management practices
      that reduce the microbial pollution in ecosystems and water sources and thus help
      to predict the risk of food and waterborne diseases. In this study we performed a
      sensitivity analysis for the KINEROS/STWIR model developed to predict the FIOs
      transport out of manured fields to other fields and water bodies in order to
      identify input variables that control the transport uncertainty. The
      distributions of model input parameters were set to encompass values found from
      three-year experiments at the USDA-ARS OPE3 experimental site in Beltsville and
      publicly available information. Sobol' indices and complementary regression trees
      were used to perform the global sensitivity analysis of the model and to explore
      the interactions between model input parameters on the proportion of FIO removed
      from fields. Regression trees provided a useful visualization of the differences
      in sensitivity of the model output in different parts of the input variable
      domain. Environmental controls such as soil saturation, rainfall duration and
      rainfall intensity had the largest influence in the model behavior, whereas soil
      and manure properties ranked lower. The field length had only moderate effect on
      the model output sensitivity to the model inputs. Among the manure-related
      properties the parameter determining the shape of the FIO release kinetic curve
      had the largest influence on the removal of FIOs from the fields. That
      underscored the need to better characterize the FIO release kinetics. Since the
      most sensitive model inputs are available in soil and weather databases or can be
      obtained using soil water models, results indicate the opportunity of obtaining
      large-scale estimates of FIO transport from fields based on publicly available
      rather than site-specific information. 

PMID- 24291763
TI  - Cytokines secreted by macrophages isolated from tumor microenvironment of
      inflammatory breast cancer patients possess chemotactic properties.
AB  - Although there is a growing literature describing the role of macrophages in
      breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is
      unclear. The aim of present study was to isolate and characterize tumor
      associated macrophages of IBC and non-IBC patients and define their role in IBC.
      Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by
      immunohistochemistry using specific monoclonal antibodies. Blood drained from
      axillary vein tributaries was collected during breast cancer surgery and the
      percentage of CD14+ in the total isolated leukocytes was assessed by flow
      cytometric analysis. CD14+ cells were separated from total leukocytes by immuno
      magnetic beads technique and were cultured overnight. Media conditioned by CD14+
      were collected and subjected to cytokine profiling using cytokine antibody array.
      Wound healing and invasion assays were used to test whether cytokines highly
      secreted by tumor drained macrophages induce motility and invasion of breast
      cancer cells. We found that macrophages highly infiltrate into carcinoma tissues
      of IBC patients. In addition blood collected from axillary tributaries of IBC
      patients is highly enriched with CD14+ cells as compared to blood collected from
      non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients
      revealed a significant increase in secretion of tumor necrosis factor-alpha;
      monocyte chemoattractant protein-1/CC-chemokine ligand 2; interleukin-8 and
      interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor
      necrosis factor-alpha, interleukin-8 and interleukin-10 significantly increased
      motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated
      from the tumor microenvironment of IBC patients secrete chemotactic cytokines
      that may augment dissemination and metastasis of IBC carcinoma cells. 

PMID- 24291765
TI  - Projecting the impact of climate change on dengue transmission in Dhaka,
      Bangladesh.
AB  - Weather variables, mainly temperature and humidity influence vectors, viruses,
      human biology, ecology and consequently the intensity and distribution of the
      vector-borne diseases. There is evidence that warmer temperature due to climate
      change will influence the dengue transmission. However, long term scenario-based
      projections are yet to be developed. Here, we assessed the impact of weather
      variability on dengue transmission in a megacity of Dhaka, Bangladesh and
      projected the future dengue risk attributable to climate change. Our results show
      that weather variables particularly temperature and humidity were positively
      associated with dengue transmission. The effects of weather variables were
      observed at a lag of four months. We projected that assuming a temperature
      increase of 3.3 degrees C without any adaptation measure and changes in socio
      economic condition, there will be a projected increase of 16,030 dengue cases in
      Dhaka by the end of this century. This information might be helpful for the
      public health authorities to prepare for the likely increase of dengue due to
      climate change. The modelling framework used in this study may be applicable to
      dengue projection in other cities. 

PMID- 24291767
TI  - FTIR, ESI-MS, VT-NMR and SANS study of trehalose thermal stabilization of
      lysozyme.
AB  - Protein aggregation is often associated with conformational and structural
      changes of secondary structure elements that may lead to exposure of some
      specific residues. Data obtained in our experimental work indicate that trehalose
      (1.0M) effectively prevent thermal inactivation and aggregation of lysozyme. In
      fact, following heat treatment, lysozyme generates insoluble aggregates which are
      almost completely absent in the samples incubated in the presence of the
      disaccharide. The experimental approach consists in studying FTIR spectra of
      intrinsic chromophores and VT-NMR measurements on lysozyme water mixtures in the
      presence of trehalose. FTIR measurements suggest that in the presence of 1.0 M of
      trehalose there is a clear decrease in the loss of alpha-helix structure and in
      the formation of intermolecularly aggregated structures. Electrospray ionization
      mass spectrometry (ESI-MS) was employed to characterize protein structural
      transition, highlighting as trehalose remarkably influenced solvent accessibility
      to the amide peptide backbone upon heat treatment, consequentially decreasing
      local protein environment changes. Complementary informations are also obtained
      by UV-vis spectroscopy measurements, Congo Red binding and activity
      determinations.

PMID- 24291766
TI  - Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in
      Seveso.
AB  - Animal evidence suggests an association between exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and adverse pregnancy outcomes. Epidemiologic
      studies report inconsistent results, but are limited by narrow range of exposure,
      small sample size, and lack of a biologic measure of highest lifetime exposure.
      On July 10, 1976, a chemical explosion in Seveso, Italy resulted in the highest
      known residential exposure to TCDD. In 1996, we initiated the Seveso Women's
      Health Study (SWHS), a retrospective cohort of TCDD exposure and reproductive
      health. Individual-level TCDD was measured in serum collected soon after the
      explosion. After 20years of follow-up, we found no association between maternal
      TCDD in 1976 serum or estimated at pregnancy and spontaneous abortion (SAB),
      fetal growth, or gestational length. Here, we present an updated analysis of TCDD
      exposure and adverse pregnancy outcomes from a subsequent follow-up of the SWHS
      cohort in 2008-2009. SWHS women had 1211 post-explosion pregnancies through the
      2008-2009 follow-up. We found no association between TCDD estimated at pregnancy
      and SAB, fetal growth, or gestational length. However, we found a non-significant
      inverse association between maternal 1976 serum TCDD and birthweight (adjusted
      beta=-22.8, 95% CI: -80.1, 34.6). The association was stronger among first post
      explosion births, but remained non-significant (adjusted beta=-47.7, 95% CI: 
      107.3, 11.9). SWHS is the first study to be able to consider two potentially
      relevant measures of TCDD exposure: highest lifetime dose and in utero. Our
      results, although non-significant, suggest that highest dose may be more relevant
      in epidemiologic studies of TCDD and pregnancy outcomes. 

PMID- 24291768
TI  - Induction of amyloidogenicity in wild type HEWL by a dialdehyde: analysis
      involving multi dimensional approach.
AB  - Physiological conditions corresponding to oxidative stress deplete the level of
      enzyme glyoxalase, facilitating a hike in the serum concentration of glyoxal.
      Simulating an elevated in vivo level of glyoxal, we tested (50%, v/v)
      concentration of glyoxal to interact with HEWL. Initially, docking study revealed
      that glyoxal binds in the hydrophobic core of the enzyme. The interaction between
      the dialdehyde (glyoxal) and the enzyme (HEWL) followed a three step transition
      involving pre-molten and molten globule states formed on days 7 and 15 of
      incubation respectively, which were characterised by an increase in the ANS
      fluorescence intensity compared to the native state. These molten globule states
      upon further incubation on day 20 resulted in the formation of aggregates which
      were characterised by an increase in ThT fluorescence intensity, red shift in
      Congo red absorbance, negative ellipticity peak at 217 nm in the far-UV CD and
      the loss of signals at 284, 290 and 294 nm in the near-UV CD spectra. Finally,
      TEM confirmed the authenticity of lysozyme fibril formation by displaying rod
      like fibrillar structure.

PMID- 24291770
TI  - Effects of early and late treatment with L-baclofen on the development and
      maintenance of tinnitus caused by acoustic trauma in rats.
AB  - Subjective tinnitus is a chronic neurological disorder in which phantom sounds
      are perceived. Recent evidence supports the hypothesis that tinnitus is related
      to neuronal hyperactivity in auditory brain regions, and consequently drugs that
      increase GABAergic neurotransmission in the CNS, such as the GABA(B) receptor
      agonist L-baclofen, may be effective as a treatment. The aim of this study was to
      investigate the effects of early (5 mg/kg s.c., 30 min and then every 24 h for 5
      days following noise exposure) and late treatment (3 mg/kg/day s.c. for 4.5 weeks
      starting at 17.5 weeks following noise exposure) with l-baclofen on the
      psychophysical attributes of tinnitus in a conditioned lick suppression model
      following acoustic trauma in rats. Acoustic trauma (a 16-kHz, 115-dB pure tone
      presented unilaterally for 1h) resulted in a significant decrease in the
      suppression ratio (SR) compared to sham controls in response to 20-kHz tones at
      2, 10 and 17.5 weeks post-exposure (P <= 0.009, P <= 0.02 and P <= 0.03,
      respectively). However, l-baclofen failed to prevent the development of tinnitus
      when administered during the first 5 days following the acoustic trauma and also
      failed to reverse it when treatment was carried out every day for 4.5 weeks. We
      also found that treatment with L-baclofen did not alter the expression of the
      GABA(B)-R2 subunit in the cochlear nucleus of noise-exposed animals.

PMID- 24291769
TI  - Advances in genomics of bony fish.
AB  - In this review, we present an overview of the recent advances of genomic
      technologies applied to studies of fish species belonging to the superclass of
      Osteichthyes (bony fish) with a major emphasis on the infraclass of Teleostei,
      also called teleosts. This superclass that represents more than 50% of all known
      vertebrate species has gained considerable attention from genome researchers in
      the last decade. We discuss many examples that demonstrate that this highly
      deserved attention is currently leading to new opportunities for answering
      important biological questions on gene function and evolutionary processes. In
      addition to giving an overview of the technologies that have been applied for
      studying various fish species we put the recent advances in genome research on
      the model species zebrafish and medaka in the context of its impact for studies
      of all fish of the superclass of Osteichthyes. We thereby want to illustrate how
      the combined value of research on model species together with a broad angle
      perspective on all bony fish species will have a huge impact on research in all
      fields of fundamental science and will speed up applications in many societally
      important areas such as the development of new medicines, toxicology test
      systems, environmental sensing systems and sustainable aquaculture strategies. 

PMID- 24291771
TI  - Interleukin-10 mediates the neuroprotection of hyperbaric oxygen therapy against
      traumatic brain injury in mice.
AB  - The aim of present study was to elucidate the role of Interleukin-10 (IL-10) in
      the neuroprotection of hyperbaric oxygen (HBO) against traumatic brain injury
      (TBI) in mice. The TBI in mice was induced by controlled cortical impact (CCI).
      HBO was given for 1h at 2.0 absolute atmosphere (ATA) in 100% O2. HBO enhanced
      the serumal and cerebral IL-10 protein levels in both sham-operated and TBI mice.
      HBO therapy after TBI reduced lesion volume, attenuated cerebral edema, improved
      neurological status including motor and cognitive function, inhibited apoptosis
      evidenced by decreased ratio of cleaved caspase-3 (C3) to pro-C3 and Bax
      expression and increased bcl-2 expression, and attenuated inflammation marked by
      reduced expression of IL-1beta, IL-6, macrophage inflammatory protein-2 (MIP-2),
      and monocyte chemoattractant protein-1 (MCP-1) and activity of matrix
      metalloproteinase-9 (MMP9). In addition, HBO after TBI improved the blood-brain
      barrier, and upregulated the expression of tight junction proteins including
      zonula occludens-1 (ZO-1) and claudin-5. IL-10 deficiency aggravated TBI-induced
      damage in the brain and abrogated the beneficial effects of HBO on
      neuroinflammation, apoptosis, and edema after TBI. IL-10 deficiency itself had no
      significant effect on brain water content and neurological status. In conclusion,
      IL-10 played an important role in the neuroprotection of HBO therapy against TBI
      in mice. 

PMID- 24291772
TI  - Acetazolamide encapsulated dendritic nano-architectures for effective glaucoma
      management in rabbits.
AB  - The present investigation was aimed to develop topically effective acetazolamide
      loaded poly(propylene imine) dendrimer nanoarchitectures and evaluate their
      intraocular pressure lowering potential. The 5.0G PPI dendrimers were synthesized
      using ethylendiamine as dendrimer core through divergent approach and
      characterized and loaded with acetazolamide (ACZ). The developed dendrimeric
      formulations were characterized for size, loading efficiency. The surface
      morphology of dendrimer was studied by Transmission Electron Microscopy. The
      developed dendrimer formulations were evaluated for hemolytic toxicity, ocular
      irritation index and intra ocular pressure reduction using normotensive adult
      male New Zealand albino rabbits as in vivo model. The maximum drug entrapment
      efficiency was found to be 56+/-2.3%. The in vitro release data of ACZ-5.0G PPI
      dendrimers showed sustained release of ACZ which was found to be 83.5+/-1.8 and
      80.4+/-1.6% in phosphate buffer saline (pH 7.4) and simulated tear fluid (pH
      7.4), respectively in 24h. Ocular irritancy, ocular residence time and
      intraocular pressure lowering effect were performed. The study revealed that in
      lower concentrations the aqueous solutions of dendrimer formulations were found
      to be weakly irritant to the eyes. The sustained and prolonged reduction in
      intraocular pressure suggested that drug entrapped in dendrimers can be used for
      higher retention in ocular cul-de sac. Further, the PPI dendrimer based
      formulation seems to enhance the ocular drug residence time and exhibits better
      intraocular pressure lowering effect for glaucoma treatment, more safely, both in
      vitro and in vivo.

PMID- 24291773
TI  - Nonsustained lead noise alert associated with repeating pattern of signals on the
      ventricular channel: is there true concern for lead malfunction?

PMID- 24291774
TI  - Changing exits in ventricular outflow tract tachycardia.

PMID- 24291776
TI  - Left atrial appendage closure: a new technique for clinical practice.
AB  - BACKGROUND/OBJECTIVE: Atrial fibrillation (AF) is the most common sustained
      cardiac arrhythmia. It is associated with increased risk for stroke mainly due to
      cardiac embolism from the left atrial appendage (LAA). Occlusion of the LAA by
      means of a device represents a valid alternative to oral anticoagulation, mainly
      in patients who cannot tolerate this therapy because of a high bleeding risk.
      Recent data on the endocardial device WATCHMAN show encouraging results for this
      patient population in terms of stroke risk reduction compared to the expected
      rate as well as in terms of implant success. This article reviews all relevant
      publications related to the main surgical and transcatheter devices used for LAA
      closure (LAAC). METHODS/RESULTS: PROTECT-AF, the first prospective randomized
      trial conducted on this technique, showed that LAA occlusion using the WATCHMAN
      was noninferior to warfarin for a combined end-point in patients with nonvalvular
      AF. There is a lack of large-scale randomized trials on long-term stroke risk in
      patients submitted to LAAC. Most studies are relatively small and focus on the
      comparison of different surgical techniques with regard to complete/incomplete
      closure success. More recently, PROTECT-AF long-term results (4-year follow-up)
      demonstrated that LAAC was statistically superior to warfarin in terms of
      efficacy. CONCLUSION: This review concludes that it is now appropriate to
      consider these techniques for patients with AF who are at high risk for stroke
      for whom effective conventional or novel anticoagulant therapy is not available
      or who present problems in managing drug treatment.

PMID- 24291775
TI  - Cardiac sympathetic denervation in patients with refractory ventricular
      arrhythmias or electrical storm: intermediate and long-term follow-up.
AB  - BACKGROUND: Left and bilateral cardiac sympathetic denervation (CSD) have been
      shown to reduce burden of ventricular arrhythmias acutely in a small number of
      patients with ventricular tachyarrhythmia (VT) storm. The effects of this
      procedure beyond the acute setting are unknown. OBJECTIVE: The purpose of this
      study was to evaluate the intermediate and long-term effects of left and
      bilateral CSD in patients with cardiomyopathy and refractory VT or VT storm.
      METHODS: Retrospective analysis of medical records for patients who underwent
      either left or bilateral CSD for VT storm or refractory VT between April 2009 and
      December 2012 was performed. RESULTS: Forty-one patients underwent CSD (14 left
      CSD, 27 bilateral CSD). There was a significant reduction in the burden of
      implantable cardioverter-defibrillator (ICD) shocks during follow-up compared to
      the 12 months before the procedure. The number of ICD shocks was reduced from a
      mean of 19.6 +/- 19 preprocedure to 2.3 +/- 2.9 postprocedure (P < .001), with
      90% of patients experiencing a reduction in ICD shocks. At mean follow-up of 367
      +/- 251 days postprocedure, survival free of ICD shock was 30% in the left CSD
      group and 48% in the bilateral CSD group. Shock-free survival was greater in the
      bilateral group than in the left CSD group (P = .04). CONCLUSION: In patients
      with VT storm, bilateral CSD is more beneficial than left CSD. The beneficial
      effects of bilateral CSD extend beyond the acute postsympathectomy period, with
      continued freedom from ICD shocks in 48% of patients and a significant reduction
      in ICD shocks in 90% of patients.

PMID- 24291778
TI  - Emerging insights into resistance to BRAF inhibitors in melanoma.
AB  - Melanoma is the most aggressive form of skin cancer. The treatment of patients
      with advanced melanoma is rapidly evolving due to an improved understanding of
      molecular drivers of this disease. Somatic mutations in BRAF are the most common
      genetic alteration found in these tumors. Recently, two different mutant
      selective small molecule inhibitors of BRAF, vemurafenib and dabrafenib, have
      gained regulatory approval based on positive results in randomized phase III
      trials. While the development of these agents represents a landmark in the
      treatment of melanoma, the benefit of these agents is limited by the frequent and
      rapid onset of resistance. The identification of several molecular mechanisms of
      resistance to BRAF inhibitors is rapidly leading to the clinical testing of
      combinatorial strategies to improve the clinical benefit of these agents. These
      mechanisms, and the lessons learned from the initial testing of the BRAF
      inhibitors, provide multiple insights that may facilitate the development of
      targeted therapies against other oncogenic mutations in melanoma, as well as in
      other cancers. 

PMID- 24291777
TI  - Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1
      expression and promotion of autophagic flux.
AB  - Heat shock protein 90 (Hsp90) has an important role in many cancers. Biochemical
      inhibitors of Hsp90 are in advanced clinical development for the treatment of
      solid and hematological malignancies. At the cellular level, their efficacy is
      diminished by the fact that Hsp90 inhibition causes activation of heat shock
      factor 1 (HSF1). We report a mechanism by which HSF1 activation diminishes the
      effect of Hsp90 inhibitors geldanamycin and 17-allylaminogeldanamycin (17-AAG,
      tanespimycin). Silencing HSF1 with siRNA or inhibiting HSF1 activity with KRIBB11
      lowers the threshold for apoptosis in geldanamycin and 17-AAG-treated cancer
      cells. Autophagy also mitigates the actions of Hsp90 inhibitors. Blocking
      autophagy with 3-methyladenine (3-MA), bafilomycin A1, or beclin 1 siRNA also
      lower the threshold for apoptosis. Exploring a potential relationship between
      HSF1 and autophagy, we monitored autophagosome formation and autophagic flux in
      control and HSF1-silenced cells. Results show HSF1 is required for autophagy in
      Hsp90 inhibitor-treated cells. The reduced autophagy observed in HSF1-silenced
      cells correlates with enhanced cell death. To investigate how HSF1 promotes
      autophagy, we monitored the expression of genes involved in the autophagic
      cascade. These data show that sequestosome 1 (p62/SQSTM1), a protein involved in
      the delivery of autophagic substrates and nucleation of autophagosomes, is an
      HSF1-regulated gene. Gene silencing was used to evaluate the significance of
      p62/SQSTM1 in Hsp90 inhibitor resistance. Cells where p62/SQSTM1 was silenced
      showed a dramatic increase in sensitivity to Hsp90 inhibitors. Results highlight
      the importance of HSF1 and HSF1-dependent p62/SQSTM1 expression in resistance
      Hsp90 inhibitors, underscoring the potential of targeting HSF1 to improve the
      efficacy of Hsp90 inhibitors in cancer. 

PMID- 24291779
TI  - Inositol-C2-PAF down-regulates components of the antigen presentation machinery
      in a 2D-model of epidermal inflammation.
AB  - In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and
      allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells
      modulate keratinocyte function via the secretion of pro-inflammatory cytokines.
      Keratinocytes then produce mediators that recruit and activate immune cells and
      amplify the inflammatory response. These pathophysiological tissue changes are
      caused by altered gene expression and the proliferation and maturation of dermal
      and epidermal cells. We recently demonstrated that the glycosidated phospholipid
      Ino-C2-PAF down-regulates a plethora of gene products associated with innate and
      acquired immune responses and inflammation in the HaCaT keratinocyte cell line.
      To further evaluate the influence of Ino-C2-PAF we established an in vitro 2D
      model of epidermal inflammation. The induction of inflammation and the impact of
      Ino-C2-PAF were assessed in this system using a genome-wide microarray analysis.
      In addition, the expression of selected genes was validated using qRT-PCR and
      flow cytometry. Treatment of the keratinocytes with a mix of proinflammatory
      cytokines resulted in transcriptional effects on a variety of genes involved in
      cutaneous inflammation and immunity, while additional treatment with Ino-C2-PAF
      counteracted the induction of many of these genes. Remarkably, Ino-C2-PAF
      suppressed the expression of a group of targets that are implicated in antigen
      processing and presentation, including MHC molecules. Thus, it is conceivable
      that Ino-C2-PAF possess therapeutic potential for inflammatory skin disorders,
      such as psoriasis and allergic contact dermatitis. 

PMID- 24291780
TI  - Dead-end complexes contribute to the synergistic inhibition of HIV-1 RT by the
      combination of rilpivirine, emtricitabine, and tenofovir.
AB  - The single tablet regimen of the nucleoside/nucleotide reverse transcriptase
      inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and
      the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is
      approved for the treatment of HIV-1 infection in treatment-naive adults. Previous
      studies have shown that two-drug combinations of these drugs show additive to
      synergistic HIV-1 antiviral activity in cell culture. In this study, two-drug
      combinations of tenofovir (TFV)+FTC, RPV+TFV, and RPV+FTC inhibited HIV-1
      replication in cell culture with strong synergy and no evidence of antagonism.
      The triple drug combination of RPV+FTC+TFV displayed moderate synergy comparable
      to efavirenz (EFV)+FTC+TFV. The formation of dead-end complexes (DEC) of HIV-1
      reverse transcriptase (RT), NRTI chain-terminated primer/template, and the next
      complementary nucleotide or NNRTIs was studied using gel mobility shift assays.
      DEC formation was seen with TFV-terminated DNA primer/template, HIV-1 RT, and FTC
      triphosphate (TP) in addition to the natural nucleotide dCTP, thus stabilizing
      chain-termination. The NNRTI RPV also formed DEC-like complexes with TFV- and FTC
      monophosphate (MP)-terminated DNA primer/templates and HIV-1 RT, and stabilized
      chain-termination by both NRTIs. Overall, the combinations of RPV, FTC, and TFV
      inhibit HIV-1 replication with moderate to strong synergy. This may be partially
      explained by enhanced DEC formation of NRTI chain-terminated DNA primer/template
      and HIV-1 RT in the presence of the other drugs in the combination, leading to
      more stable chain-termination and replication inhibition by NRTIs. 

PMID- 24291781
TI  - Endovenous laser ablation of varicose veins with the 1470 nm diode laser using a
      radial fiber - 1-year follow-up.
AB  - BACKGROUND: Endovenous laser ablation is one of the most accepted treatment
      options for insufficient great and small saphenous veins. The aim of this study
      was to investigate the long-term efficacy and safety of the radial fiber (ELVeS
      radial kitTM) for the 1470 nm diode laser in a 1-year follow-up. METHODS: A total
      of 308 lower limbs with primary insufficiency of great and small saphenous veins
      or insufficient tributaries were included in the prospective observational cohort
      study. The primary efficacy endpoint of the study was ultrasonographic proven
      elimination of venous reflux after at least 1 year. Secondary efficacy and
      further safety end points after 1 year were as follows: (1) sonographic exclusion
      of recanalization of the treated vein segments, (2) deep vein thrombosis,
      clinical pulmonary embolism or superficial vein thrombosis as defined by
      objective testing, (3) death from any cause, (4) persistent clinical complaints
      such as pain and paresthesia, (5) recurrent varicose veins. Patient satisfaction
      was assessed using a CIVIQ-2 questionnaire after 1 year. RESULTS: Follow-up could
      be completed in 91.2% of the patients. Excellent efficacy numbers with 99.6%
      occlusion of the treated varicose veins as elimination of reflux could be
      demonstrated. After 1 year, 96% of the treated veins disappeared completely
      sonographically; one recanalization was observed. No deep vein thrombosis or
      pulmonary embolism occurred, three superficial vein thrombosis were diagnosed in
      follow-up examinations. Four patients died, not related to pulmonary embolism. No
      persistent pain or paresthesia occurred in the follow-up. Recurrent varicose
      veins were diagnosed in 10 patients (2.81%). CONCLUSION: One-year follow-up
      showed that endovenous laser treatment of varicose veins with 1470 nm diode laser
      using the radial fiber is highly effective, also regarding in a 1-year follow-up.

PMID- 24291782
TI  - Investigation of effect of edaravone on ischemic stroke.
AB  - A novel free radical scavenger, edaravone, has been demonstrated to exert a
      neuroprotective effect and improve outcomes in acute ischemic stroke, but there
      have been few clinical studies. Therefore, we investigated retrospectively
      whether the administration of edaravone at the acute stage of ischemic stroke can
      improve outcomes of the disease at the time of discharge. Between January 1998
      and December 2011, 625 consecutive patients (331 males and 294 females: mean age
      77.0 years, range 36-101 years) with acute ischemic stroke who were admitted to
      our institution within 48 hours after stroke onset were enrolled. Subtypes of
      strokes were lacunar infarction (LI) in 188 (30.0%), atherothrombotic infarction
      (ATCI) in 268 (42.0%), and cardioembolic infarction (CEI) in 169 (27.0%). Of the
      625 patients, 237 (37.0%) received both edaravone and conventional treatment,
      while the other 388 (62.0%) patients underwent conventional treatment only. As a
      conventional treatment, 422 (67.0%) of 625 patients were treated with ozagrel
      sodium, and 37 patients received argatroban. The overall outcomes at discharge
      were favorable (modified Rankin Scale score 0-2) in 296 (47.4%) and death
      occurred (mRS score 6) in 86 (13.8%). In a univariate analysis, the
      administration of edaravone did not have a significant effect on total death from
      all types of cerebral infarction. However, treatment with edaravone showed a
      favorable tendency (p=0.099) compared to conventional treatment after adjustments
      for age and gender. Further investigation is required before a definite
      conclusion can be made. 

PMID- 24291783
TI  - Dynamics of vessel wall changes following the implantation of the absorb
      everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality
      study at 6, 12, 24 and 36 months.
AB  - AIMS: To assess observations with multimodality imaging of the Absorb
      bioresorbable everolimus-eluting vascular scaffold performed in two consecutive
      cohorts of patients who were serially investigated either at 6 and 24 months or
      at 12 and 36 months. METHODS AND RESULTS: In the ABSORB multicentre single-arm
      trial, 45 patients (cohort B1) and 56 patients (cohort B2) underwent serial
      invasive imaging, specifically quantitative coronary angiography (QCA),
      intravascular ultrasound (IVUS), radiofrequency backscattering (IVUS-VH) and
      optical coherence tomography (OCT). Between one and three years, late luminal
      loss remained unchanged (6 months: 0.19 mm, 1 year: 0.27 mm, 2 years: 0.27 mm, 3
      years: 0.29 mm) and the in-segment angiographic restenosis rate for the entire
      cohort B (n=101) at three years was 6%. On IVUS, mean lumen, scaffold, plaque and
      vessel area showed enlargement up to two years. Mean lumen and scaffold area
      remained stable between two and three years whereas significant reduction in
      plaque behind the struts occurred with a trend toward adaptive restrictive
      remodelling of EEM. Hyperechogenicity of the vessel wall, a surrogate of the
      bioresorption process, decreased from 23.1% to 10.4% with a reduction of
      radiofrequency backscattering for dense calcium and necrotic core. At three
      years, the count of strut cores detected on OCT increased significantly, probably
      reflecting the dismantling of the scaffold; 98% of struts were covered. In the
      entire cohort B (n=101), the three-year major adverse cardiac event rate was
      10.0% without any scaffold thrombosis. CONCLUSIONS: The current investigation
      demonstrated the dynamics of vessel wall changes after implantation of a
      bioresorbable scaffold, resulting at three years in stable luminal dimensions, a
      low restenosis rate and a low clinical major adverse cardiac events rate.
      CLINICAL TRIAL REGISTRATION INFORMATION:
      http://www.clinicaltrials.gov/ct2/show/NCT00856856.

PMID- 24291785
TI  - Therapeutic perspectives of Eph-ephrin system modulation.
AB  - Eph receptors are the largest class of kinase receptors and, together with their
      ligands ephrins, they have a primary role in embryogenesis. Their expression has
      been found deregulated in several cancer tissues and, in many cases, abnormal
      levels of these proteins have been correlated to a poor prognosis. Recently, the
      Eph-ephrin system was found to be deregulated in other pathological processes,
      involving the nervous and cardiovascular systems. The increasing body of evidence
      supports the Eph-ephrin system as a target not only for the treatment of solid
      tumors, but also to face other critical diseases such as amyotrophic lateral
      sclerosis and diabetes driving current efforts toward the development of
      pharmacological tools potentially able to treat these pathologies. 

PMID- 24291786
TI  - The utility of biomarkers in CNS drug development.

PMID- 24291784
TI  - Back to the future! The evolving role of maintenance therapy after hematopoietic
      stem cell transplantation.
AB  - Relapse is a devastating event for patients with hematologic cancers treated with
      hematopoietic stem cell transplantation. In most situations, relapse treatment
      options are limited. Maintenance therapy offers the possibility of delaying or
      avoiding disease recurrence, but its role remains unclear in most conditions that
      we treat with transplantation. Here, Dr. Hourigan presents an overview of minimal
      residual disease (MRD) measurement in hematologic malignancies and the
      applicability of MRD-based post-transplantation interventions. Dr. McCarthy
      reviews current knowledge of maintenance therapy in the autologous
      transplantation context, with emphasis on immunologic interventions and immune
      modulation strategies designed to prevent relapse. Dr. de Lima discusses current
      lines of investigation in disease recurrence prevention after allogeneic
      transplantation, focusing on acute myeloid leukemia and myelodysplastic syndrome.

PMID- 24291787
TI  - Virtual pharmaceutical companies: collaborating flexibly in pharmaceutical
      development.
AB  - Research and development (R&D) collaborations represent one approach chosen by
      the pharmaceutical industry to tackle current challenges posed by declining
      internal R&D success rates and fading of the blockbuster model. In recent years,
      a flexible concept to collaborate in R&D has emerged: virtual pharmaceutical
      companies (VPCs). These differ from other R&D companies, such as biotech start
      ups, collaborating with big pharmaceutical companies, because they solely
      comprise experienced teams of managers. VPCs have only been described anecdotally
      in literature. Thus, we present here the characteristics of a VPC and suggest how
      big pharma can leverage the concept of VPCs by introducing five possible modes of
      collaboration. We find that one mode, investing, is particularly promising for
      big pharma. 

PMID- 24291788
TI  - Strong neutrino cooling by cycles of electron capture and beta- decay in neutron
      star crusts.
AB  - The temperature in the crust of an accreting neutron star, which comprises its
      outermost kilometre, is set by heating from nuclear reactions at large densities,
      neutrino cooling and heat transport from the interior. The heated crust has been
      thought to affect observable phenomena at shallower depths, such as thermonuclear
      bursts in the accreted envelope. Here we report that cycles of electron capture
      and its inverse, beta(-) decay, involving neutron-rich nuclei at a typical depth
      of about 150 metres, cool the outer neutron star crust by emitting neutrinos
      while also thermally decoupling the surface layers from the deeper crust. This
      'Urca' mechanism has been studied in the context of white dwarfs and type Ia
      supernovae, but hitherto was not considered in neutron stars, because previous
      models computed the crust reactions using a zero-temperature approximation and
      assumed that only a single nuclear species was present at any given depth. The
      thermal decoupling means that X-ray bursts and other surface phenomena are
      largely independent of the strength of deep crustal heating. The unexpectedly
      short recurrence times, of the order of years, observed for very energetic
      thermonuclear superbursts are therefore not an indicator of a hot crust, but may
      point instead to an unknown local heating mechanism near the neutron star
      surface. 

PMID- 24291789
TI  - Biochemical reconstitution of topological DNA binding by the cohesin ring.
AB  - Cohesion between sister chromatids, mediated by the chromosomal cohesin complex,
      is a prerequisite for faithful chromosome segregation in mitosis. Cohesin also
      has vital roles in DNA repair and transcriptional regulation. The ring-shaped
      cohesin complex is thought to encircle sister DNA strands, but its molecular
      mechanism of action is poorly understood and the biochemical reconstitution of
      cohesin activity in vitro has remained an unattained goal. Here we reconstitute
      cohesin loading onto DNA using purified fission yeast cohesin and its loader
      complex, Mis4(Scc2)-Ssl3(Scc4) (Schizosaccharomyces pombe gene names appear
      throughout with their more commonly known Saccharomyces cerevisiae counterparts
      added in superscript). Incubation of cohesin with DNA leads to spontaneous
      topological loading, but this remains inefficient. The loader contacts cohesin at
      multiple sites around the ring circumference, including the hitherto enigmatic
      Psc3(Scc3) subunit, and stimulates cohesin's ATPase, resulting in efficient
      topological loading. The in vitro reconstitution of cohesin loading onto DNA
      provides mechanistic insight into the initial steps of the establishment of
      sister chromatid cohesion and other chromosomal processes mediated by cohesin. 

PMID- 24291790
TI  - Role of Tet1 in erasure of genomic imprinting.
AB  - Genomic imprinting is an allele-specific gene expression system that is important
      for mammalian development and function. The molecular basis of genomic imprinting
      is allele-specific DNA methylation. Although it is well known that the de novo
      DNA methyltransferases Dnmt3a and Dnmt3b are responsible for the establishment of
      genomic imprinting, how the methylation mark is erased during primordial germ
      cell (PGC) reprogramming remains unclear. Tet1 is one of the ten-eleven
      translocation family proteins, which have the capacity to oxidize 5
      methylcytosine (5mC), specifically expressed in reprogramming PGCs. Here we
      report that Tet1 has a critical role in the erasure of genomic imprinting. We
      show that despite their identical genotype, progenies derived from mating between
      Tet1 knockout males and wild-Peg10 and Peg3, which exhibit aberrant
      hypermethylation in the paternal allele of differential methylated regions
      (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next
      generation due to paternal loss of Tet1 function. Genome-wide DNA methylation
      analysis of embryonic day 13.5 PGCs and sperm of Tet1 knockout mice revealed
      hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to
      PGCs. Analysis of the DNA methylation dynamics in reprogramming PGCs indicates
      that Tet1 functions to wipe out remaining methylation, including imprinted genes,
      at the late reprogramming stage. Furthermore, we provide evidence supporting the
      role of Tet1 in the erasure of paternal imprints in the female germ line. Thus,
      our study establishes a critical function of Tet1 in the erasure of genomic
      imprinting. 

PMID- 24291791
TI  - Efficient ethanol production from brown macroalgae sugars by a synthetic yeast
      platform.
AB  - The increasing demands placed on natural resources for fuel and food production
      require that we explore the use of efficient, sustainable feedstocks such as
      brown macroalgae. The full potential of brown macroalgae as feedstocks for
      commercial-scale fuel ethanol production, however, requires extensive re
      engineering of the alginate and mannitol catabolic pathways in the standard
      industrial microbe Saccharomyces cerevisiae. Here we present the discovery of an
      alginate monomer (4-deoxy-L-erythro-5-hexoseulose uronate, or DEHU) transporter
      from the alginolytic eukaryote Asteromyces cruciatus. The genomic integration and
      overexpression of the gene encoding this transporter, together with the necessary
      bacterial alginate and deregulated native mannitol catabolism genes, conferred
      the ability of an S. cerevisiae strain to efficiently metabolize DEHU and
      mannitol. When this platform was further adapted to grow on mannitol and DEHU
      under anaerobic conditions, it was capable of ethanol fermentation from mannitol
      and DEHU, achieving titres of 4.6% (v/v) (36.2 g l(-1)) and yields up to 83% of
      the maximum theoretical yield from consumed sugars. These results show that all
      major sugars in brown macroalgae can be used as feedstocks for biofuels and value
      added renewable chemicals in a manner that is comparable to traditional arable
      land-based feedstocks.

PMID- 24291794
TI  - Enhanced production of Fumigaclavine C in liquid culture of Aspergillus fumigatus
      under a two-stage process.
AB  - Fumigaclavine C (FC) produced by Aspergillus fumigatus is a conidiation
      associated ergot alkaloid with strong anti-inflammatory activity. However, its
      wide application has been severely limited by low FC production from submerged
      culture. In this work, a novel two-stage culture process by combining shake
      culture with static culture was proposed to enhance the production of FC. After
      the process optimization, the FC production reached 62.7 mg/L, which was
      significantly higher than ever report. For scaling up this new culture process,
      the gas-liquid interfacial area per unit volume (Agas-liq) was identified as the
      key factor. The results showed that in a combined stirred-static bioreactor
      system, a maximum FC production (58.97 mg/L) was obtained at an Agas-liq value of
      1.30 cm(2)/mL. These results demonstrated that two-stage culture is an efficient
      strategy to enhance FC production and the information obtained will be useful to
      production of this powerful bioactive compound on a large scale.

PMID- 24291793
TI  - Primitive layered gabbros from fast-spreading lower oceanic crust.
AB  - Three-quarters of the oceanic crust formed at fast-spreading ridges is composed
      of plutonic rocks whose mineral assemblages, textures and compositions record the
      history of melt transport and crystallization between the mantle and the sea
      floor. Despite the importance of these rocks, sampling them in situ is extremely
      challenging owing to the overlying dykes and lavas. This means that models for
      understanding the formation of the lower crust are based largely on geophysical
      studies and ancient analogues (ophiolites) that did not form at typical mid-ocean
      ridges. Here we describe cored intervals of primitive, modally layered gabbroic
      rocks from the lower plutonic crust formed at a fast-spreading ridge, sampled by
      the Integrated Ocean Drilling Program at the Hess Deep rift. Centimetre-scale,
      modally layered rocks, some of which have a strong layering-parallel foliation,
      confirm a long-held belief that such rocks are a key constituent of the lower
      oceanic crust formed at fast-spreading ridges. Geochemical analysis of these
      primitive lower plutonic rocks--in combination with previous geochemical data for
      shallow-level plutonic rocks, sheeted dykes and lavas--provides the most
      completely constrained estimate of the bulk composition of fast-spreading oceanic
      crust so far. Simple crystallization models using this bulk crustal composition
      as the parental melt accurately predict the bulk composition of both the lavas
      and the plutonic rocks. However, the recovered plutonic rocks show early
      crystallization of orthopyroxene, which is not predicted by current models of
      melt extraction from the mantle and mid-ocean-ridge basalt differentiation. The
      simplest explanation of this observation is that compositionally diverse melts
      are extracted from the mantle and partly crystallize before mixing to produce the
      more homogeneous magmas that erupt.

PMID- 24291795
TI  - Xylitol production at high temperature by engineered Kluyveromyces marxianus.
AB  - Several recombinant Kluyveromyces marxianus strains were constructed through
      overexpressing the Neurospora crassa xylose reductase genes. YZJ015, which
      maintained the original xylitol dehydrogenase gene, produced xylitol with the
      highest productivity (1.49 g L(-1) h(-1)) from 100 g L(-1) xylose at 42  degrees
      C. Even at 45  degrees C, YZJ015 was still able to produce 60.03 g L(-1) xylitol
      from 100 g L(-1) xylose with a productivity of 1.25 g L(-1)h(-1). In addition,
      for 20 rounds of cell recycling at 42  degrees C, YZJ015 produced 71.35 g L(-1)
      xylitol from 100 g L(-1) xylose with a productivity of 4.43 g L(-1) h(-1) per
      cycle. YZJ017, in which the xylitol dehydrogenase gene was disrupted, produced
      100.02 g L(-1) xylitol at a yield of 1.01 g g(-1) from 100 g L(-1) xylose with 40
      g L(-1) glycerol as co-substrate at 42  degrees C. These engineered strains
      provide an excellent foundation for xylitol production at elevated temperatures.

PMID- 24291792
TI  - Mechanism of farnesylated CAAX protein processing by the intramembrane protease
      Rce1.
AB  - CAAX proteins have essential roles in multiple signalling pathways, controlling
      processes such as proliferation, differentiation and carcinogenesis. The ~120
      mammalian CAAX proteins function at cellular membranes and include the Ras
      superfamily of small GTPases, nuclear lamins, the gamma-subunit of heterotrimeric
      GTPases, and several protein kinases and phosphatases. The proper localization of
      CAAX proteins to cell membranes is orchestrated by a series of post-translational
      modifications of the carboxy-terminal CAAX motifs (where C is cysteine, A is an
      aliphatic amino acid and X is any amino acid). These reactions involve
      prenylation of the cysteine residue, cleavage at the AAX tripeptide and
      methylation of the carboxyl-prenylated cysteine residue. The major CAAX protease
      activity is mediated by Rce1 (Ras and a-factor converting enzyme 1), an
      intramembrane protease (IMP) of the endoplasmic reticulum. Information on the
      architecture and proteolytic mechanism of Rce1 has been lacking. Here we report
      the crystal structure of a Methanococcus maripaludis homologue of Rce1, whose
      endopeptidase specificity for farnesylated peptides mimics that of eukaryotic
      Rce1. Its structure, comprising eight transmembrane alpha-helices, and catalytic
      site are distinct from those of other IMPs. The catalytic residues are located
      ~10 A into the membrane and are exposed to the cytoplasm and membrane through a
      conical cavity that accommodates the prenylated CAAX substrate. We propose that
      the farnesyl lipid binds to a site at the opening of two transmembrane alpha
      helices, which results in the scissile bond being positioned adjacent to a
      glutamate-activated nucleophilic water molecule. This study suggests that Rce1 is
      the founding member of a novel IMP family, the glutamate IMPs. 

PMID- 24291796
TI  - Comparison of mesophilic and thermophilic anaerobic digestion of sugar beet pulp:
      performance, dewaterability and foam control.
AB  - Digestion of sugar beet pulp was assessed in relation to biogas and methane
      production, foaming potential, and digestate dewaterability. Four 4-litre working
      volume digesters were operated mesophilically (37+/-0.5  degrees C) and four
      thermophilically (55+/-0.5  degrees C) over three hydraulic retention times.
      Digesters were operated in duplicate at organic loading rates (OLR) of 4 and 5 g
      volatile solids l(-1) day(-1) without water addition. Thermophilic digestion gave
      higher biogas and methane productivity than mesophilic and was able to operate at
      the higher OLR, where mesophilic digestion showed signs of instability. Digestate
      dewaterability was assessed using capillary suction time and frozen image
      centrifugation. The occurrence of, or potential for, stable foam formation was
      assessed using a foaming potential test. Thermophilic operation allowed higher
      loadings to be applied without loss of performance, and gave a digestate with
      superior dewatering characteristics and very little foaming potential.

PMID- 24291797
TI  - Comparison between a fixed bed hybrid membrane bioreactor and a conventional
      membrane bioreactor for municipal wastewater treatment: a pilot-scale study.
AB  - A hybrid membrane bioreactor (HMBR) was developed, by adding biofilm support
      media into a conventional membrane bioreactor (CMBR), and operated in parallel
      with a CMBR. Results showed that effluent quality was significantly better with
      the HMBR. The removal efficiencies of COD, BOD5, NH4(+)-N and TN with the HMBR
      were 84%, 98%, 97% and 75%, respectively, as compared to 80%, 96%, 93% and 38%
      with the CMBR. There were no differences in phosphorus removal. The membrane
      fouling rate in the HMBR was on average only 57% of that in the CMBR. The lower
      concentration of colloidal biopolymer clusters in the HMBR sludge, probably due
      to their retention by the biofilm, could be partially responsible for this
      difference. Filterability and settleability of the sludge were also better in the
      HMBR. Consequently, it is concluded that the addition of fixed support media for
      biofilm growth can improve the performance of CMBRs.

PMID- 24291798
TI  - Evaluation of analytical tools and multivariate methods for quantification of co
      former crystals in ibuprofen-nicotinamide co-crystals.
AB  - Co-crystals are multicomponent substances designed by the addition of two or more
      different molecules in a same crystallographic pattern, in which it differs from
      the crystallographic motif of its co-formers. The addition of highly soluble
      molecules, like nicotinamide, in the crystallographic pattern of ibuprofen
      enhances its solubility more than 7.5 times, improving the properties of this
      widely used drug. Several analytical solid state techniques are used to
      characterize the ibuprofen-nicotinamide co-crystal, being the most used: mid
      infrared (ATR-FTIR), differential scanning calorimetry (DSC), X-ray diffraction
      (XRPD) and Raman spectroscopy. These analytical solid state techniques were
      evaluated to quantify a mixture of ibuprofen-nicotinamide co-crystal and its co
      formers in order to develop a calibration model to evaluate the co-crystal purity
      after its synthesis. Raman spectroscopy showed better result than all other
      techniques with a combination of multivariate calibration tools, presenting lower
      values of calibration and prediction errors. The partial least squares regression
      model gave a mean error lower than 5% for all components presented in the
      mixture. DSC and mid-infrared spectroscopy proved to be insufficient for
      quantification of the ternary mixture. XRPD presented good results for
      quantification of the co-formers, ibuprofen and nicotinamide, but fair results
      for the co-crystal. This is the first report of quantification of ibuprofen
      nicotinamide co-crystal, among its co-formers. The quantification is of great
      importance to determine the yield of the co-crystallization reactions and the
      purity of the product obtained. 

PMID- 24291799
TI  - Characterization of in vitro and in vivo metabolites of carnosic acid, a natural
      antioxidant, by high performance liquid chromatography coupled with tandem mass
      spectrometry.
AB  - Carnosic acid (CA) is a widely employed antioxidant and the main active component
      in rosemary and sage, but its metabolism remains largely unknown. The present
      study investigated the metabolism of CA in vitro and in vivo for the first time,
      using high performance liquid chromatography coupled with hybrid triple
      quadrupole-linear ion trap mass spectrometry (HPLC-Q-trap-MS). A couple of scan
      modes were adopted in mass spectrometer domain, including Q1 full scan, neutral
      loss scan-information dependent acquisition-enhanced product ion (NL-IDA-EPI) and
      precursor ion scan-information dependent acquisition-enhanced product ion (PI-IDA
      EPI). In particular, a prediction was carried out on the basis of in vitro
      metabolism results, and gave birth to a multiple ion monitoring-information
      dependent acquisition-enhanced product ion (MIM-IDA-EPI) mode aiming to detect
      the trace metabolites in CA-treated biological samples. A total of ten
      metabolites (M4-13), along with three degradative products (M1-3), were
      identified for CA from in vitro metabolism models, including liver microsomes of
      human and rats (HLMs and RLMs), human intestinal microsomes (HIMs) and two
      species of Cunninghamella elegans. Twelve (U1-12) and six (F1-6) metabolites were
      detected from CA-treated urine and feces, respectively. In addition, five
      metabolites (SM2-6) in vivo were purified and definitely identified using NMR
      spectroscopy. The results of both in vitro and in vivo metabolism studies
      indicated poor metabolic stability for CA, and the glucuronidation and oxidation
      metabolisms extensively occurred for CA in vitro, while oxidation,
      glucuronidation and methylation were the main metabolic pathways observed in
      vivo. 

PMID- 24291800
TI  - An eco-friendly strategy, using on-line monitoring and dilution coupled to a
      second-order chemometric method, for the construction of dissolution curves of
      combined pharmaceutical associations.
AB  - A simple, precise, economic and minimally operator-dependent method was developed
      under green analytical chemistry principles, for the simultaneous construction of
      the dissolution curves of a pharmaceutical association in short time and without
      employing organic solvents, allowing important savings of labor and resources.
      The carvedilol (CAR) and hydrochlorothiazide (HCT) combined formulation was
      employed as a model. The method (OD/UV-MCR) involves on-line sample dilution (OD)
      and UV detection of the analytes, coupled to multivariate curve resolution with
      alternating least squares (MCR-ALS). OD/UV-MCR proved to be robust and was
      successfully validated in accordance to ICH guidelines, fulfilling acceptance
      criteria for specificity (r(2) of spectral correlation>0.950), linearity [r>0.999
      (N=25) in the ranges 1.00-31.1mg l(-1) and 0.51-15.2mg l(-1) for CAR and HCT,
      respectively] and precision (RSD<2%). Accuracy was assessed by point-to-point
      comparison between the dissolution profiles furnished by the proposed method with
      those provided by HPLC analysis, evidencing the usefulness of this monitoring
      system. In addition, OD/UV-MCR was successfully employed for the comparative
      analysis of three lots of commercial formulations of the CAR-HCT pharmaceutical
      association, belonging to a couple of different brands, employing Moore and
      Flanner's f2 similarity indicator.

PMID- 24291801
TI  - Suboptimal choice by pigeons: an analog of human gambling behavior.
AB  - Human gambling often involves the choice of a low probability but high valued
      outcome over a high probability (certain) low valued outcome (not gambling) that
      is economically more optimal. We have developed an analog of gambling in which
      pigeons prefer a suboptimal alternative that infrequently provides a signal for a
      high probability (or high magnitude) of reinforcement over an optimal alternative
      that always provides a signal for a lower probability (or lower magnitude) of
      reinforcement. We have identified two mechanisms that may be responsible for this
      suboptimal behavior. First, the effect of nonreinforcement results in
      considerably less inhibition of choice than ideally it should. Second, the
      frequency of the occurrence of the signal for a high probability or high
      magnitude of reinforcement is less important than ideally it should. Also
      analogous to human gambling is the finding that pigeons that are normally food
      restricted choose suboptimally, whereas those that are minimally food restricted
      choose optimally. In addition, pigeons that are singly housed choose
      suboptimally, whereas those that are exposed to a more enriched environment
      choose less suboptimally. We believe that these findings have implications for
      the understanding and treatment of problem gambling behavior. 

PMID- 24291802
TI  - Epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells.
AB  - The trabecular meshwork (TM) is a major component of the conventional outflow
      pathway and the excess extracellular matrix (ECM), and fibrosis in the TM causes
      increased outflow resistance. In this study, we first investigated the effects of
      several ECM components in the induction of an epithelial mesenchymal transition
      (EMT)-like phenomenon in TM cells. TM cells were isolated from cynomolgus monkeys
      (Macaca fascicularis). The cells were cultured in ECM-coated dishes and then
      subjected to both western blot analysis and immunocytochemistry to measure the
      levels of EMT-associated markers. Cell motility was assessed using wound healing
      and chemotaxis assays. We found that type I collagen, fibronectin and laminin
      induced the dissociation of cell-cell contact and elongation of actin stress
      fibers in the cultured monkey TM cells. In addition, following the same
      stimulation of the ECM, the expression of mesenchymal markers, such as
      fibronectin and alpha-smooth muscle actin, and the phosphorylation of Smad2
      increased in the TM cells. Our results showed the significant acceleration of TM
      cellular motility following stimulation with type I collagen, fibronectin and
      laminin. These phenomena were inhibited by the c-Jun N-terminal kinase (JNK)
      inhibitor SP600125. In addition, siRNA against paxillin was transfected to
      evaluate the association between paxillin and the EMT-like phenomenon. The
      knockdown of paxillin expression by transfection with siRNA blocked the EMT-like
      alteration of the cellular characteristics and chemotaxis toward transforming
      growth factor-beta2 in the cultured TM cells. Our results showed that the ECM-JNK
      paxillin pathway induced an EMT-like phenomenon in TM cells, resulting in the
      abundant expression of fibronectin and activation of motility in TM cells. This
      EMT-like phenomenon could result in aberrant conditions in the aqueous outflow
      pathway in glaucomatous eyes. 

PMID- 24291803
TI  - Polarization enhancement and ferroelectric switching enabled by interacting
      magnetic structures in DyMnO3 thin films.
AB  - The mutual controls of ferroelectricity and magnetism are stepping towards
      practical applications proposed for quite a few promising devices in which
      multiferroic thin films are involved. Although ferroelectricity stemming from
      specific spiral spin ordering has been reported in highly distorted bulk
      perovskite manganites, the existence of magnetically induced ferroelectricity in
      the corresponding thin films remains an unresolved issue, which unfortunately
      halts this step. In this work, we report magnetically induced electric
      polarization and its remarkable response to magnetic field (an enhancement of
      ~800% upon a field of 2 Tesla at 2 K) in DyMnO3 thin films grown on Nb-SrTiO3
      substrates. Accompanying with the large polarization enhancement, the
      ferroelectric coercivity corresponding to the magnetic chirality switching field
      is significantly increased. A picture based on coupled multicomponent magnetic
      structures is proposed to understand these features. Moreover, different magnetic
      anisotropy related to strain-suppressed GdFeO3-type distortion and Jahn-Teller
      effect is identified in the films.

PMID- 24291804
TI  - Do ethnic differences in cord blood leptin levels differ by birthweight category?
      Findings from the Born in Bradford cohort study.
AB  - BACKGROUND: There is evidence that South Asian individuals have higher fat mass
      for a given weight than Europeans. One study reported that the greater fatness
      for a given birthweight may increase with increasing birth weight, suggesting
      that any attempt to increase mean birth weight in South Asians would markedly
      increase their fatness. OBJECTIVE: Our objective was to examine whether
      differences in cord leptin values between White British and Pakistani infants
      vary by birth weight category. METHOD: We examined the difference in cord leptin
      levels between 659 White British and 823 Pakistani infants recruited to the Born
      in Bradford cohort study, by clinical categories and thirds of the birth weight
      distribution. RESULTS: Pakistani infants had a lower mean birthweight but higher
      cord leptin levels than White British infants [ratio of geometric mean(RGM) of
      cord leptin adjusted for birth weight = 1.36 (95% CI 1.26,1.46)]. Birthweight was
      positively associated with cord leptin levels in both groups, with no evidence
      that the regression lines in the two groups diverged from each other with
      increasing birthweight.The relative ethnic difference in cord leptin was similar
      in low (<2500 g), normal and high (>=4000 g) birthweight infants(P-value for
      interaction = 0.91). It was also similar across thirds of the birthweight
      distribution [RGM (95% CI) in lowest, mid and highest thirds were 1.37 (1.20,
      1.57), 1.36 (1.20, 1.54) and 1.31 (1.16, 1.52), respectively, P-interaction =
      0.51]. CONCLUSIONS: We found marked differences in cord leptin levels between
      Pakistani and White British infants but no evidence that this difference
      increases with increasing birthweight.

PMID- 24291805
TI  - Real-time measurement of flow rate in microfluidic devices using a cantilever
      based optofluidic sensor.
AB  - Real-time and accurate measurement of flow rate is an important reqirement in lab
      on a chip (LOC) and micro total analysis system (MUTAS) applications. In this
      paper, we present an experimental and numerical investigation of a cantilever
      based optofluidic flow sensor for this purpose. Two sensors with thin and thick
      cantilevers were fabricated by engraving a 2D pattern of cantilever/base on two
      polymethylmethacrylate (PMMA) slabs using a CO2 laser system and then casting a
      2D pattern with polydimethylsiloxane (PDMS). The basic working principle of the
      sensor is the fringe shift of the Fabry-Perot (FP) spectrum due to a changing
      flow rate. A Finite Element Method (FEM) is used to solve the three dimensional
      (3D) Navier-Stokes and structural deformation equations to simulate the pressure
      distribution, velocity and cantilever deflection results of the flow in the
      channel. The experimental results show that the thin and thick cantilevers have a
      minimum detectable flow change of 1.3 and 4 (MUL min(-1)) respectively. In
      addition, a comparison of the numerical and experimental deflection of the
      cantilever has been done to obtain the effective Young's modulus of the thin and
      thick PDMS cantilevers. 

PMID- 24291807
TI  - Tracking chemical reactions on the surface of filamentous phage using mass
      spectrometry.
AB  - Chemical modification of phage libraries has allowed the in vitro evolution of
      ligands having properties not provided by natural polypeptides. The development
      of novel and more diverse chemical reactions on phage was hampered by the lack of
      analytical methods to efficiently monitor the reaction products on the more than
      10 000 kDa large filamentous phage particles. Herein, we present a strategy to
      detect chemically modified peptides on phage based on enzymatic release of
      peptide from phage and mass spectrometry analysis. 

PMID- 24291806
TI  - Aging and individual differences in binding during sentence understanding:
      evidence from temporary and global syntactic attachment ambiguities.
AB  - We report an investigation of aging and individual differences in binding
      information during sentence understanding. An age-continuous sample of adults
      (N=91), ranging from 18 to 81 years of age, read sentences in which a relative
      clause could be attached high to a head noun NP1, attached low to its modifying
      prepositional phrase NP2 (e.g., The son of the princess who scratched
      himself/herself in public was humiliated), or in which the attachment site of the
      relative clause was ultimately indeterminate (e.g., The maid of the princess who
      scratched herself in public was humiliated). Word-by-word reading times and
      comprehension (e.g., who scratched?) were measured. A series of mixed-effects
      models were fit to the data, revealing: (1) that, on average, NP1-attached
      sentences were harder to process and comprehend than NP2-attached sentences; (2)
      that these average effects were independently moderated by verbal working memory
      capacity and reading experience, with effects that were most pronounced in the
      oldest participants and; (3) that readers on average did not allocate extra time
      to resolve global ambiguities, though older adults with higher working memory
      span did. Findings are discussed in relation to current models of lifespan
      cognitive development, working memory, language experience, and the role of
      prosodic segmentation strategies in reading. Collectively, these data suggest
      that aging brings differences in sentence understanding, and these differences
      may depend on independent influences of verbal working memory capacity and
      reading experience.

PMID- 24291809
TI  - Comparison of polypropylene mesh and porcine-derived, cross-linked urinary
      bladder matrix materials implanted in the rabbit vagina and abdomen.
AB  - INTRODUCTION AND HYPOTHESES: Our aim was to compare histological and
      biomechanical effects of polypropylene (PP) mesh and porcine-derived, cross
      linked urinary bladder matrix (cUBM) graft materials using a rabbit vaginal and
      abdominal model. METHODS: Forty rabbits were implanted with PP mesh (n = 20) or
      cUBM (n = 20) in the vagina and abdomen. Two grafts (PP or cUBM) of the same type
      were placed into each site, so each rabbit had four grafts. Grafts were harvested
      12 weeks later and processed for histologic analysis and biomechanical testing.
      RESULTS: There were high rates of two types of grafts missing in the vagina.
      Vaginal PP was associated with erosion reaction (67%), whereas abdominal PP and
      cUBM showed no sign of erosion. All patches adhered to rectus abdominis or
      vaginal mucosa and shrank to varying degrees, especially for PP grafts. Compared
      with vaginal PP, vaginal cUBM induced milder chronic inflammation response, had
      lower scores (P = 0.000) for inflammation response, and showed higher scores for
      neovascularization (P = 0.000) and fibroblastic proliferation (P = 0.002). In the
      abdomen, both histopathological parameters were insignificantly different (P >
      0.05) between cUBM and PP. The mechanical properties of UBM did not deteriorate
      following implantation, whereas the ultimate tensile strength and elastic modulus
      of vaginal PP increased. PP had higher scores for tensile and break strength than
      did cUBM (P < 0.05). CONCLUSIONS: The cUBM has good biocompatibility, high
      ability to integrate with the vagina, and maintains mechanical properties in
      vivo. It may be a promising material for pelvic floor reconstruction.

PMID- 24291811
TI  - Residents'corner September 2013. sQUIZ your knowledge! Necrotic papules in a
      patient with symptoms from gastrointestinal tract and central nervous system.

PMID- 24291812
TI  - Residents'corner July 2013. Nail it! Painful toe nails in a young patient.

PMID- 24291808
TI  - Effects of cochlear ablation on amino acid levels in the rat cochlear nucleus and
      superior olive.
AB  - Amino acids have important roles in the chemistry of the auditory system,
      including communication among neurons. There is much evidence for glutamate as a
      neurotransmitter from auditory nerve fibers to cochlear nucleus neurons. Previous
      studies in rodents have examined effects of removal of auditory nerve input by
      cochlear ablation on levels, uptake and release of glutamate in cochlear nucleus
      subdivisions, as well as on glutamate receptors. Effects have also been reported
      on uptake and release of gamma-aminobutyrate (GABA) and glycine, two other amino
      acids strongly implicated in cochlear nucleus synaptic transmission. We mapped
      the effects of cochlear ablation on the levels of amino acids, including
      glutamate, GABA, glycine, aspartate, glutamine, taurine, serine, threonine, and
      arginine, in microscopic subregions of the rat cochlear nucleus. Submicrogram
      size samples microdissected from freeze-dried brainstem sections were assayed for
      amino acid levels by high performance liquid chromatography. After cochlear
      ablation, glutamate and aspartate levels decreased by 2 days in regions receiving
      relatively dense innervation from the auditory nerve, whereas the levels of most
      other amino acids increased. The results are consistent with a close association
      of glutamate and aspartate with auditory nerve fibers and of other amino acids
      with other neurons and glia in the cochlear nucleus. A consistent decrease of
      GABA level in the lateral superior olive could be consistent with a role in some
      lateral olivocochlear neurons. The results are compared with those obtained with
      the same methods for the rat vestibular nerve root and nuclei after vestibular
      ganglionectomy. 

PMID- 24291814
TI  - Novel materials for biofilm reactors and their characterization.
AB  - The application of adherently growing microorganisms for biotechnological
      production processes is established, but it is still a niche technology with only
      a small economic impact. However, novel approaches are under development for new
      types of biofilm reactors. In this context, increasingly more microstructured
      metal surfaces are being investigated, and they show positive effects on the
      bacterial growth and the biofilm establishment. However, for comparison of the
      data, the different surface materials have to correspond in their different
      characteristics, such as wettability and chemical composition. Also, new
      materials, such as plastic composite supports, were developed. To understand the
      interaction between these new materials and the biofilm-producing microorganisms,
      different surface science methods have to be applied to reveal a detailed
      knowledge of the surface characteristics. In conclusion, microstructured surfaces
      show a high potential for enhanced biofilm growth, probably accompanied by an
      enhanced productivity of the microorganisms.

PMID- 24291817
TI  - Gas phase electronic spectra of carbon chains C(n) (n = 6-9).
AB  - Ultraviolet electronic transitions of the linear carbon chains C6, C7, C8, and C9
      were measured in the gas phase by a mass-resolved 1 + 1 resonant two-photon
      ionization technique using a picosecond laser. Broad absorptions with band maxima
      at 230.2 and 259.0 nm are identified as N(3)Sigma(u)(-) - X(3)Sigma(g)(-) (N > 3)
      transition of C6 and C8, respectively. Based on calculated Franck-Condon
      intensities, the band maxima are identified as origin bands. An upper limit of 30
      ps is determined for the N(3)Sigma(u)(-) excited state lifetime of C6. The
      (1)Sigma(u)(+)- X(1)Sigma(g)(+) transition with band maximum at 238.5 nm was
      observed for C7 and at 279.0 nm for C9. The proposition that intramolecular
      processes in the excited electronic states of carbon chains can lead to
      broadening as in the diffuse interstellar absorptions is experimentally
      demonstrated.

PMID- 24291815
TI  - Efficient generation of lung and airway epithelial cells from human pluripotent
      stem cells.
AB  - The ability to generate lung and airway epithelial cells from human pluripotent
      stem cells (hPSCs) would have applications in regenerative medicine, modeling of
      lung disease, drug screening and studies of human lung development. We have
      established, based on developmental paradigms, a highly efficient method for
      directed differentiation of hPSCs into lung and airway epithelial cells. Long
      term differentiation of hPSCs in vivo and in vitro yielded basal, goblet, Clara,
      ciliated, type I and type II alveolar epithelial cells. The type II alveolar
      epithelial cells were capable of surfactant protein-B uptake and stimulated
      surfactant release, providing evidence of specific function. Inhibiting or
      removing retinoic acid, Wnt and BMP-agonists to signaling pathways critical for
      early lung development in the mouse-recapitulated defects in corresponding
      genetic mouse knockouts. As this protocol generates most cell types of the
      respiratory system, it may be useful for deriving patient-specific therapeutic
      cells. 

PMID- 24291816
TI  - Potential mechanisms of aberrant DNA hypomethylation on the x chromosome in
      uterine leiomyomas.
AB  - We recently found that aberrant DNA hypomethylation is more common on the X
      chromosome than on other chromosomes in uterine leiomyomas by genome-wide DNA
      methylation profiling. To investigate the mechanism of aberrant hypomethylation
      on the X chromosome in uterine leiomyomas, we analyzed methylome and
      transcriptome data from three cases of leiomyomas and the adjacent myometrium. We
      found that eleven of the aberrantly hypomethylated genes on the X chromosome were
      common to the three cases. None of these 11 genes were transcriptionally
      upregulated in the leiomyoma. However, one of them, TSPYL2, was hypomethylated in
      68% of multiple leiomyoma specimens. The incidence of aberrant hypomethylation of
      TSPYL2 was comparable to that of the MED12 mutation (68%), which is known to be
      detected at a high frequency in uterine leiomyomas. We also analyzed the
      aberration of the X chromosome inactivation (XCI) mechanism in uterine
      leiomyomas. Hypomethylation was not enriched in the imprinted genes, suggesting
      that dysfunction of polycomb repressive complexes is not involved in the aberrant
      hypomethylation on the X chromosome. The expression analysis of XCI-related genes
      revealed that the XIST and SATB1 expression was downregulated in 36% and 46% of
      11 leiomyoma specimens, respectively, while the HNRNPU and SMCHD1 expression was
      not altered. In conclusion, the aberration of XCI-related genes such as SATB1 or
      XIST may be involved in aberrant hypomethylation on the X chromosome in a certain
      population of the patients with uterine leiomyomas. TSPYL2 of the aberrantly
      hypomethylated genes on the X chromosome can be used as a biomarker of uterine
      leiomyomas. 

PMID- 24291818
TI  - Molecular insights on TNKS1/TNKS2 and inhibitor-IWR1 interactions.
AB  - Tankyrases (TNKS) belong to the poly(ADP-ribose)polymerase (PARP) protein super
      family and play a vital role in the Wnt/beta-catenin signaling pathway. TNKS is a
      potential target for therapeutic intervention against various cancers, heritable
      diseases (e.g. cherubism) and implications in the replication of herpes simplex
      virus (HSV). The recent discovery of the structure of TNKS with an IWR1 inhibitor
      has provided insight into the binding modes which are specific for the TNKS
      protein which will aid in the development of drugs that are specific for the TNKS
      protein. The current study investigates molecular interactions between the
      induced pocket of TNKS1 and TNKS2 with an IWR1 compound using computational
      approaches. Molecular docking analysis of IWR1 at the induced pocket of TNKS1 and
      TNKS2 was performed. The resulting protein-ligand complexes were simulated for a
      timescale of 100 ns. Results revealed the stable binding of IWR1 at the induced
      pocket of TNKS1 and TNKS2 proteins. Apart from active site amino acids, pi-pi
      stack paring interactions were also crucial for the protein-ligand binding and
      stability of the complex. Further, energy-optimized pharmacophore mapping was
      performed and the resulting pharmacophore model contained a four (TNKS1-IWR1) and
      five (TNKS2-IWR1) featured sites. Based on the pharmacophore models, the best
      inhibitors were screened from the ZINC natural product compound database and
      these could be used as potential drugs against TNKS1 and TNKS2. 

PMID- 24291820
TI  - Stability engineering of the human antibody repertoire.
AB  - Human monoclonal antibodies often display limited thermodynamic and colloidal
      stabilities. This behavior hinders their production, and places limitations on
      the development of novel formulation conditions and therapeutic applications.
      Antibodies are highly diverse molecules, with much of the sequence variation
      observed within variable domain families and, in particular, their
      complementarity determining regions. This has complicated the development of
      comprehensive strategies for the stability engineering of the human antibody
      repertoire. Here we provide an overview of the field, and discuss recent advances
      in the development of robust and aggregation resistant antibody therapeutics. 

PMID- 24291821
TI  - Heterogeneity of glycolytic oscillatory behaviour in individual yeast cells.
AB  - There are many examples of oscillations in biological systems and one of the most
      investigated is glycolytic oscillations in yeast. These oscillations have been
      studied since the 1950s in dense, synchronized populations and in cell-free
      extracts, but it has for long been unknown whether a high cell density is a
      requirement for oscillations to be induced, or if individual cells can oscillate
      also in isolation without synchronization. Here we present an experimental method
      and a detailed kinetic model for studying glycolytic oscillations in individual,
      isolated yeast cells and compare them to previously reported studies of single
      cell oscillations. The importance of single-cell studies of this phenomenon and
      relevant future research questions are also discussed. 

PMID- 24291822
TI  - Reduced integrity of sensorimotor projections traversing the posterior limb of
      the internal capsule in children with congenital hemiparesis.
AB  - There is reduced integrity of corticospinal projections that traverse the
      posterior limb of the internal capsule (PLIC) in children with unilateral
      cerebral palsy (CP). It remains unclear whether there are changes in integrity of
      other projections traversing the PLIC. Forty children with congenital hemiparesis
      and 15 typically developing children underwent structural and diffusion-weighted
      MRI. All children with congenital hemiparesis showed lesions to the
      periventricular white matter. Structural images were parcellated into 34 cortical
      regions per hemisphere and posterior limb of the internal capsule was identified.
      PLIC connections to each cortical region were extracted using probabilistic
      tractography. Differences between hemispheres for each cortical projection
      (asymmetry index (AI)) and tract microstructure (fractional anisotropy (FA), mean
      diffusivity (MD)) were assessed. The results showed that 17 children (42.5%) with
      congenital hemiparesis showed bilateral lesions on structural MRI. Projections to
      the primary motor cortex (precentral gyrus and paracentral lobule) showed greater
      asymmetry in unilateral CP group compared to typically developing children and
      indicate reduced projections on the hemisphere contralateral to the impaired limb
      (i.e., contralateral hemisphere). Reduced FA and increased MD were also observed
      for connections with the primary motor cortex, primary sensory cortex
      (postcentral gyrus) and precuneus on the contralateral hemisphere in children
      with congenital hemiparesis. Similar changes were observed between children with
      unilateral and bilateral lesions on structural MRI. Notably, microstructural
      changes were associated with deficits in both sensory and motor function. The
      findings further unravel the underlying neuroanatomical correlates of
      sensorimotor deficits in children with congenital hemiparesis. 

PMID- 24291823
TI  - Alignment-free phylogenetics and population genetics.
AB  - Phylogenetics and population genetics are central disciplines in evolutionary
      biology. Both are based on comparative data, today usually DNA sequences. These
      have become so plentiful that alignment-free sequence comparison is of growing
      importance in the race between scientists and sequencing machines. In
      phylogenetics, efficient distance computation is the major contribution of
      alignment-free methods. A distance measure should reflect the number of
      substitutions per site, which underlies classical alignment-based phylogeny
      reconstruction. Alignment-free distance measures are either based on word counts
      or on match lengths, and I apply examples of both approaches to simulated and
      real data to assess their accuracy and efficiency. While phylogeny reconstruction
      is based on the number of substitutions, in population genetics, the distribution
      of mutations along a sequence is also considered. This distribution can be
      explored by match lengths, thus opening the prospect of alignment-free population
      genomics. 

PMID- 24291824
TI  - ER stress upregulated PGE2/IFNgamma-induced IL-6 expression and down-regulated
      iNOS expression in glial cells.
AB  - The disruption of endoplasmic reticulum (ER) function can lead to
      neurodegenerative disorders, in which inflammation has also been implicated. We
      investigated the possible correlation between ER stress and immune function using
      glial cells. We demonstrated that ER stress synergistically enhanced
      prostaglandin (PG) E2 + interferon (IFN) gamma-induced interleukin (IL)-6
      production. This effect was mediated through cAMP. Immune-activated glial cells
      produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress
      inhibited PGE2 + IFNgamma-induced iNOS expression. Similar results were obtained
      when cells were treated with dbcAMP + IFNgamma. Thus, cAMP has a dual effect on
      immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS
      expression under ER stress. Therefore, our results suggest a link between ER
      stress and immune reactions in neurodegenerative diseases.

PMID- 24291826
TI  - [Overcoming neurological diseases-breakthrough for new era].
AB  - Neurological diseases have long been thought to be difficult or intractable to be
      cured. Recent progress in researches on etiologies and pathogeneses of many
      neurological diseases, however, has made it become possible to treat some
      diseases such as bulbo-spinal muscular atrophy and Alzheimer's disease not only
      symptomatically but also in the sense of disease modification. We may be at the
      entrance of a new era where many neurological diseases would become treatable and
      overcome. My individual experiences studying 3 diseases, namely, distal myopathy
      with rimmed vacuoles, amyotrophic lateral sclerosis and spinocerebellar ataxia
      were presented and through them the following massages were conveyed to young
      neurologists of the Japanese Society of Neurology (JSN); To tackle the case even
      there is no similar case in the literature because you are the only one who could
      help the patient and some clues must be found, To cooperate with other colleagues
      and patients because you are not alone, To be reasonable, logical or scientific,
      To always be innovative or seek better situations, and To be global or
      international sharing real time information with other peoples in the world. JSN
      will make great leaps to the goals under the mission to contribute happiness of
      peoples in Japan and other countries through neurology including neurological
      practice, education and research. 

PMID- 24291825
TI  - Multiple divergent haplotypes express completely distinct sets of class I MHC
      genes in zebrafish.
AB  - The zebrafish is an important animal model for stem cell biology, cancer, and
      immunology research. Histocompatibility represents a key intersection of these
      disciplines; however, histocompatibility in zebrafish remains poorly understood.
      We examined a set of diverse zebrafish class I major histocompatibility complex
      (MHC) genes that segregate with specific haplotypes at chromosome 19, and for
      which donor-recipient matching has been shown to improve engraftment after
      hematopoietic transplantation. Using flanking gene polymorphisms, we identified
      six distinct chromosome 19 haplotypes. We describe several novel class I U
      lineage genes and characterize their sequence properties, expression, and
      haplotype distribution. Altogether, ten full-length zebrafish class I genes were
      analyzed, mhc1uba through mhc1uka. Expression data and sequence properties
      indicate that most are candidate classical genes. Several substitutions in
      putative peptide anchor residues, often shared with deduced MHC molecules from
      additional teleost species, suggest flexibility in antigen binding. All ten
      zebrafish class I genes were uniquely assigned among the six haplotypes, with
      dominant or codominant expression of one to three genes per haplotype.
      Interestingly, while the divergent MHC haplotypes display variable gene copy
      number and content, the different genes appear to have ancient origin, with
      extremely high levels of sequence diversity. Furthermore, haplotype variability
      extends beyond the MHC genes to include divergent forms of psmb8. The many
      disparate haplotypes at this locus therefore represent a remarkable form of
      genomic region configuration polymorphism. Defining the functional MHC genes
      within these divergent class I haplotypes in zebrafish will provide an important
      foundation for future studies in immunology and transplantation. 

PMID- 24291827
TI  - [Immunology for understanding the pathogenesis of multiple sclerosis].
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS) and the pathogenesis leading to demyelination
      includes 3 major processes. The first step is establishment of autoimmunity to
      CNS myelin components, with molecular mimicry between a portion of the infectious
      agents and that of myelin, which is an important feature. The second step is
      entry of immune cells into the CNS via the blood-brain barrier (BBB). Activated T
      cells can easily cross the BBB using surface LFA-1 and VLA-4 as ligands to ICAM-1
      and VCAM-1, respectively, which are expressed on endothelial cells in the CNS. As
      the third step, immune reactions occur within the CNS when activated T cells
      encounter specific antigens presented by microglia. Of the helper T cells re
      stimulated by autoantigens, Th1 cells producing interferon-gamma and Th17 cells
      secreting interleukin-17 play major roles in propagating inflammation, while Th2
      cells producing IL-4, and regulatory T cells secreting IL-10 and TGF-beta
      suppress pathological processes. Final demyelination is rendered either by
      macrophages recruited from the bloodstream across the BBB, or by TNF-alpha and
      nitric oxide, which are secreted by Th1 cells and macrophages, and toxic to CNS
      myelin. 

PMID- 24291828
TI  - [Conflict of interest of clinical research in Japan].

PMID- 24291829
TI  - [Gene mutations; up date].
AB  - The advance of sequencing technology, the exome analysis using next-generation
      sequencing (NGS), of the human genome has dramatically accelerated biomedical
      research and about 2,900 causative gene tests are now available. The discoveries
      of the causative genes for hereditary neurodegenerative diseases accelerated the
      studies on the pathophysiologic mechanisms of diseases and therapeutic
      strategies. Genome-wide association studies (GWAS) have successfully revealed
      numerous susceptibility genes for "common diseases" and neurodegenerative
      diseases with low odds ratios associated with risk alleles. It is expected that
      the dramatic advance of genome analysis and regenerative medicine by ES and iPS
      research bring a paradigm shift in clinical practice. The nationwide discussion
      for biomedical ethics in this personal genome era is absolutely needed. 

PMID- 24291830
TI  - [Essential knowledge of drugs for neurologists on pharmacokinetics and drug
      development in global aspects to the world].
AB  - In the last 30 years, a lot of drugs to treat neurological disorders have been
      developed. Now neurology is one of the fields where the medication is the most
      important factor deciding the prognosis of the treated patients. Neurologists are
      now required to have precise knowledge of drug metabolisms and interactions on
      the medication to treat neurological disorders. Insert Packages contain most
      useful and important information for medications, however, information for the
      drugs are not enough to prescribe some drugs, and even though in the same drugs,
      information offered is different especially on drug interactions. Pharmacists and
      physicians should choose the drugs which offer proper and useful drug information
      to treat patients. Developments of drugs to treat patients are important as a
      physician in Japan. It can also contribute to treat patients in the all of the
      world. The role of neurologists is especially big because the drugs of the brain
      are rapidly developed than any other fields in medicine. 

PMID- 24291831
TI  - [Update on deep brain stimulation for movement disorders].
AB  - Deep brain stimulation (DBS) has been widely performed for various medically
      refractory movement disorders. For Parkinson disease (PD), target of DBS is
      subthalamic nucleus (STN) or globus pallidus internus (GPi). There are some
      evidences to demonstrate its effectiveness on motor function and QOL. DBS
      effectively improves levodopa-responsive motor symptoms, and significantly
      reduces dyskinesia and motor fluctuations. STN DBS particularly decreases the
      need for dopaminergic medication. A combination of medical treatment and DBS
      would provide longer relief of motor symptoms than medical treatment only.
      Currently new evidence supporting early introduction of DBS for better future
      outcome is published. DBS of Vim thalamus has been indicated for intractable
      tremor with various etiologies. Recently posterior subthalamic area (PSA) is
      introduced as an alternative target to Vim for tremor. GPi DBS is also effective
      treatment option for generalized dystonia. 

PMID- 24291832
TI  - [Differential diagnosis and common pathology between Alzheimer's disease and
      vascular dementia].
AB  - Dementia due to both Alzheimer's disease (AD) and cerebrovascular disease (CVD)
      is designated as mixed dementia, or alternatively, AD with CVD. Cerebral amyloid
      angiopathy almost always accompanies AD, and causes lobar microbleeds, cortical
      subarachnoid hemorrhage and cortical microinfarctions. Dementia exclusively with
      cerebral amyloid angiopathy is a form of vascular dementia, while it is
      classified to AD when significant Alzheimer's pathology coexists. Between AD and
      vascular dementia there are common and overlapping pathologies, which is
      important for differential diagnosis of these diseases. 

PMID- 24291833
TI  - [Macroscopic findings of brains are helpful in differential diagnosis of
      neurological disorders].
AB  - Neuropathological diagnosis is essential in neurological disorders. Neurological
      signs and neuroimaging play a major role in clinical diagnosis. Although
      neuroimaging indicates the location and size of lesions, which is useful to
      longitudinal evaluation of edema or atrophy, pathological diagnosis is absolutely
      necessary to qualitative diagnosis. The first step of pathological diagnosis
      starts to observe macroscopic findings of brains, which reveal the distribution
      of lesions specific to individual disorders. Since the macroscopic abnormal
      findings are based on the microscopic degenerative findings, it may be no
      exaggeration to say that macroscopic findings enable to make neuropathological
      diagnosis. Accuracy of macroscopic finding is corrected or revised with
      microscopic findings and finally compared with neuroimaging and clinical
      diagnosis. Therefore it is very important and useful to learn macroscopic
      findings of neurological disorders. 

PMID- 24291834
TI  - [Problems with countermeasures for health insurance treatment in neurology].
AB  - In order to tackle with the high price of new technology and new therapeutic
      drugs, Central Social Insurance Medical Council in Japan has begun to discuss the
      possibility to introduce technology assessment in the actual public health
      insurance system. It is indispensable to minimize the economic burden of patients
      to deliver technological advances in treatment. It is important for the physician
      to recognize the economic burden of patients and to reduce this burden as much as
      possible. Around 69% of the cancer patients had economic worries (n = 2037) in
      our survey "Economic burden of patient with cancer from the viewpoint of cancer
      economics". The mean out-of-pocket expense (752,000 yen) of the patients without
      economic worries was three-fourths that of the patients (987,000 yen) with
      economic worries. The out-of pocket expenses and the refunds/benefits were
      1,217,000 yen and 652,000 yen for molecular targeted treatment (n = 494). The
      Intractable Diseases Control Act is to be enacted in 2016-17 to promote work on
      nanbyo control using all the resources of the nation, and this act should surely
      entail financial support.

PMID- 24291835
TI  - [Neurology in Japan before World War II].
AB  - Modern Western medicine was introduced into Japan by a Dutch doctor Pompe van
      Meerdervoort in 1855. A German physician EOE von Balz devoted himself to
      educating medicine at Tokyo Medical School, the predecessor of the present
      University of Tokyo for 25 years. Hiroshi Kawahara and Kinnosuke Miura, pioneers
      of Japan Neurology, received their education by him. Kawahara first described X
      linked bulvo-spinal muscular atrophy, and published the first Japanese textbook
      of clinical neurology in 1897. In 1902, Miura and others founded the Japanese
      Society of Neuro-Psychiatry, the forerunner of the present " Japanese Society of
      Neurology ". Both Seizo Katsunuma, Professor of Nagoya University, and Junnjiro
      Kato, Professor of Tohoku University, succeeded Miura's neurology. Miura
      investigated into the cause of beriberi, but ended in failure. Hasegawa's
      proposal at the Diet in 1894 that the Japan Government should found an
      independent department of neurology in the University of Tokyo was unfortunately
      rejected. There was no foundation of independent institute, department and clinic
      of neurology before World War II. Consequently Japanese neurology was on the ebb
      at that time. 

PMID- 24291836
TI  - [Positron emission tomography in neurological disorders].

PMID- 24291837
TI  - [Neurorehabilitation for spinocerebellar degeneration].
AB  - It remains to be elucidated whether there is a use- or dose-dependent effect of
      rehabilitative intervention on impairment and disability of spinocerebellar
      degeneration since the disease progressively damages cerebellar structure that
      plays a crucial role in motor learning. Moreover there is a trade-off between
      functional improvement after rehabilitation and functional deterioration due to
      disease progression. Recent clinical trials from Germany and Japan have
      demonstrated that comprehensive intensive rehabilitation focusing on balance
      function have immediate and lasting effect up to 1 year on ataxia and gait
      disorder in patients with spinocerebellar degeneration. For sustained gain after
      the intensive rehabilitation, customized attempts to boost patients' daily
      activities according to their ability appears to be important. 

PMID- 24291838
TI  - [Basic knowledge about Kampo for neurologists].
AB  - Kampo is a traditional form of medicine in Japan. The individual formulas of the
      Kampo medicines consist mainly of plant-derived crude drugs. Recently, extract
      products that maintain specific levels of quality have been commonly used for
      dosage formulation instead of decoction. Although severe side effects, including
      pseudoaldosteronism, interstitial pneumonitis, liver damage and mesenteric
      phlebosclerosis may occasionally arise in some patients, herbal formulations are
      generally safe compared with potent western medicines. Since the complicated
      interaction of a Kampo formulation is difficult to analyze pharmacologically, the
      use of each Kampo formula has been based on the empirical rules described in
      classical writings by clinicians. Currently, formula selection is not always
      based on the pathological recognition from the Oriental medicine perspective,
      because these ancient theories are not necessarily amenable to current clinical
      practice. Nevertheless, formula selection would be more appropriate, and the
      therapeutic efficacy would increase if the physicians understood the basic
      concepts of ki, ketsu, sui, yin-yang, hypofunction and hyperfunction, heat and
      cold, superficies and interior, the five parenchymatous viscera and the six
      stages of disease. Regardless of the primary diseases, many Kampo formulas are
      considered to be indicated for patients complaining of headache, dizziness and
      numbness, which are common symptoms in everyday practice in neurology. 

PMID- 24291839
TI  - [Kampo medicines as useful therapeutic agents in clinical practice of neurology:
      case reports & representative medicines].
AB  - Doctors in any department should have at least minimum knowledge of Kampo
      medicines. However, doctors who specialize in neurology often have inadequate
      knowledge of Kampo medicines. The efficacy of Kampo medicines in treating
      intractable diseases such as neurodegenerative diseases is not adequately
      understood and needs to be investigated in the future. On the other hand, Kampo
      medicines are often effective for treating common symptoms such as headache,
      dysesthesia, pain, and vertigo, encountered in daily medical practice. Because
      many patients suffer from these symptoms, the impact of these symptoms on our
      society is not small, even though the causes of these symptoms are not crucial.
      Having the skill to prescribe even a dozen or so Kampo medicines (for example,
      goshuyuto, goreisan, goshajinkigan, sokeikakketsuto) increases the treatment
      options and may be very beneficial in daily medical practice. In this article, I
      provide instructions on the use of representative Kampo medicines and present
      some case reports to elucidate their use. Amassing and sharing clinical
      experiences regarding the use of Kampo medicines would strengthen the medical
      evidences of Kampo medicines.

PMID- 24291840
TI  - [MicroRNA in neurodegenerative disorders].
AB  - MicroRNAs (miRNAs) bind to the 3'-untranslated region of mRNA, and thereby
      suppress the gene expression. Recent studies suggest that miRNAs modify the
      pathogenesis of cancer and neurodegeneration. Our study demonstrated that the
      expression levels of miR-196a is increased in a mouse model of spinal and bulbar
      muscular atrophy (SBMA), a neurodegenerative disease caused by the expansion of
      polyglutamine in androgen receptor (AR). In cultured neuronal cells, miR-196a
      decayed the mutant AR mRNA via silencing CUG triplet repeat RNA binding protein
      2, a potent miR-196a targeting mRNA, which contributed to stabilize the mutant AR
      mRNA. Adeno-associated virus vector-mediated delivery of this miRNA attenuates
      the expression of the mutant AR, resulting in the mitigation of motor neuron
      degeneration in the SBMA mice. Introduction of miRNA appears to be a novel
      therapeutic strategy for devastating neurodegenerative diseases. 

PMID- 24291841
TI  - [Epilepsy and higher brain dysfunction].

PMID- 24291842
TI  - [Central Institute for the Molecular Pathomechanisms of Epilepsies].

PMID- 24291843
TI  - [Inclusion body myopathy with Paget's disease of bone and frontotemporal
      dementia].
AB  - Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia
      (IBMPFD) is an autosomal dominant disease caused by mutations in the VCP gene.
      VCP encodes a well-conserved multifunctional protein, valosin containing protein
      (VCP), which has important roles in protein quality control via proteasome and
      autophagy, protein aggregation, quality control of mitochondria, cell
      proliferation, and so on. Clinically, muscle weakness is the most common symptom
      of which disease onset is around 40 years. Affected muscles are variable, and the
      patients are sometimes diagnosed as limb girdle muscular dystrophy or GNE
      myopathy. Muscle pathology shows characteristic features including
      cytoplasmic/nuclear inclusions, rimmed vacuoles, and disorganized myofibrills,
      together with neurogenic changes. Paget's disease of bone is reported to be
      observed in a half of the patients around the age of 40 years, but less common in
      Japanese patients. Frontotemporal dementia is seen around one third of the
      patients which appears nearly 10 years later than muscle or bone disease. In
      addition to cognitive dysfunctions, motor neuron involvement and cerebellar signs
      were also seen in our series. IBMPFD is not so rare disease as previously
      thought, but complicate clinical findings may make its diagnosis difficult. 

PMID- 24291844
TI  - [How do the interventional neurologists function in the clinical setting?].
AB  - Neuroendovascular therapy is a rapidly evolving clinical subspecialty because of
      its minimal invasiveness and novel device development. In Japan, neurosurgeons
      perform a substantial portion of neuroendovascular procedures, however, the
      number of neurologists who certified by the Japanese Society for
      Neuroendovascular Therapy (interventional neurologist) is gradually increasing.
      Neurologists tend to deal with medical treatment in the acute stage and
      prevention of ischemic stroke, in addition, neuroendovascular procedures for
      ischemic cerebrovascular diseases performed by neurologists themselves, such as
      acute revascularization therapy for acute intracranial major artery occlusion or
      carotid artery stenting, might provide various benefits to ischemic stroke
      patients because of the smooth, seamless and close management from admission, to
      intervention, to discharge and after discharge. Because of insufficient number of
      interventionists to perform emergent neurointerventional procedures in the
      clinical setting of acute ischemic stroke in Japan, we wish that more
      neurologists get interested in and receive training in the neuroendovascular
      therapy. 

PMID- 24291845
TI  - [Alzheimer disease: experimental approaches to genetic and environmental risk
      factors].

PMID- 24291847
TI  - [Brain-machine interface (BMI) - application to neurological disorders].
AB  - Brain-machine interface (BMI) is a new technology to receive input from the brain
      which is translated to operate a computer or other external device in real time.
      After significant progress during the recent 10 years, this technology is now
      very close to the clinical use to restore neural functions of patients with
      severe neurologic impairment. This technology is also a strong tool to
      investigate the mode of neuro-signal processing in the brain and to understand
      the mechanism of neural dysfunction which leads to the development of novel
      neurotechnology for the treatment of various sorts of neurological disorders. 

PMID- 24291846
TI  - [World of functional RNA].
AB  - The development of next-generation sequences has brought not only high-throughput
      sequencing but also new possibilities for various kinds of analysis methods of
      genetic information. Dr. Hayashizaki et al. developed new technologies to
      construct the full-length cDNA library and applied them to high-throughput
      sequencing technologies for large-scale transcriptome analysis. These analysis
      results overturned the conventional assumption the 2% of the genome is
      transcribed by showing that 70% or more of the genome is transcribed as RNA
      through FANTOM activities which was founded in 2000 on their initiative. Further,
      the existence of 23,000 non-protein coding RNAs was confirmed. These new findings
      redefine the central dogma into a new picture containing new interaction cascade
      and the unexpected complexity of combined omics. The neo central dogma shows that
      there are three types of final products derived from genes; long ncRNA, small
      ncRNA, and protein. They play essential roles by forming complexes with each
      other to maintain life. Long ncRNA and small ncRNA play a role as a ligand with
      sequence information. Long ncRNA and protein play a role as a functional
      molecule. Here, I would like to introduce the neo central dogma concept and some
      of the mechanisms of ncRNAs. 

PMID- 24291848
TI  - [Role of neurosurgical management in movement disorders other than Parkinson
      disease].
AB  - Neurosurgical procedures are indispensable in management of various types of
      movement disorders (MD). Stereotactic operations that have been well established
      include deep brain stimulation for tremor, dystonia, and Parkinsonian symptoms.
      Recently the actual role of stereotactic ablative procedures such as thalamotomy
      and pallidotomy has been re-explored, and Vo thalamotomy shows long-term
      improvement of task specific focal dystonia like writer's cramp and musician's
      dystonia. A new less invasive treatment of tremor using MR guided focused
      ultrasound has started and is promising. Intrathecal administration of baclofen
      is also an established treatment for severe spasticity, but other ablative
      procedures such as peripheral neurotomy and dorsal rhizotomy are also important
      in spasticity treatment. It seems that most neurologists are unfamiliar, at least
      in Japan, with such neurosurgical procedures. However, neurologists involved in
      management of MD should understand the important roles of neurosurgical
      management of intractable MD and should refer such patients to appropriate
      neurosurgeons before permanent contracture and deformity develop.

PMID- 24291849
TI  - [Pathogenesis and treatment of brachial plexus neuritis].
AB  - Neuralgic amyotrophy (NA, also known as Parsonage-Turner syndrome) is a distinct
      peripheral nervous system (PNS) disorder, characterized by sudden attacks of
      severe neuropathic pain usually in the shoulder and/or arm. The neuralgia
      commonly disappears after a few days to weeks, and consequently patchy paresis
      with amyotrophy appears. The available evidence suggests that NA is essentially
      idiopathic immune-mediated neuritis of the brachial plexus, and also has a
      complex pathogenesis that includes an underlying predisposition, susceptibility
      to dysfunction of some PNS structure, and a trigger for the attacks, such as
      viral infection, vaccination, trauma, surgery, and strenuous exercise. Genetic
      factors also contribute to the pathogenesis of NA, and thus, this disorder occurs
      in both idiopathic and hereditary forms, but hereditary one is considered to be
      10 times less common than idiopathic one. NA has been considered to be self
      limiting, benign disorder showing good recovery without specific treatments.
      However, recent studies have indicated that the long-term prognosis of NA is less
      favorable than has been assumed. In 2009, a Cochrane review identified one open
      label, retrospective series, the results of which suggested that administration
      of corticosteroids in the acute phase of NA could shorten the duration of painful
      symptoms and also accelerate recovery in some patients. We recently have reported
      that intravenous immunoglobulin (IVIg) with methylpredonisolone pulse therapy is
      effective for motor impairment of NA. 

PMID- 24291850
TI  - [Non-motor symptoms in premotor phase of Parkinson disease].
AB  - Non-motor symptoms are common in patients with newly diagnosed Parkinson's
      disease (PD), and some even predate the emergence of the classic motor features.
      The premotor phase of PD is characterized by several important non-motor
      features, including constipation, olfactory dysfunction, REM sleep behavior
      disorder (RBD), depression, etc. The basis of this prodromal stage is that the
      pathological process related to Lewy bodies, may start outside of the substantia
      nigra. We investigated 469 Japanese PD patients in our multicenter study, using
      the Japanese version of the RBD screening questionnaire. Probable RBD was
      detected in 146 patients (31%) and the RBD symptoms of 53 patients preceded the
      onset of PD motor symptoms. With the probable exception of RBD, non-motor
      clinical markers can be sensitive for an impending diagnosis of PD, but these
      features are common and non-specific. The combination of non-motor clinical
      markers and more specific markers (e.g., imaging or genetic markers) may achieve
      sufficient utility in PD diagnosis and prediction in future. Being able to
      diagnose that a patient has PD at an earlier time point than is currently
      possible, would be allowed to introduce potential disease-modifying therapies at
      a time when it could have fundamental and long-lasting effects.

PMID- 24291851
TI  - [Initial diagnosis of Parkinson's disease - neuroradiological diagnosis].
AB  - Brain MRI is essential for differentiating Parkinson's disease (PD) from other
      parkinsonian syndromes. The purpose of performing brain MRI is not to make a
      diagnosis of PD but is to exclude other parkinsonian syndromes. Recently, several
      new MRI techniques such as voxel based morphometry, relaxometry, magnetization
      transfer, spectroscopy, tractography, and functional MRI have been introduced in
      the diagnosis of PD. Neuromelanin imaging is one of the new techniques and can be
      useful to make an initial diagnosis of PD. MIBG myocardial scintigraphy is a
      sensitive imaging tool to differentiate PD from other parkinsonian syndromes and
      is one of the good tools to make an initial diagnosis of PD. Brain perfusion
      imaging is sometimes useful to make an initial diagnosis of PD, because reduced
      brain perfusion area can be detected before brain MRI detects morphological
      changes of the brain. Dopamine transporter imaging, not available in Japan, is a
      sensitive tool to detect very early parkinsonism and is useful to make an initial
      diagnosis of PD. However, it is difficult to differentiate PD from other
      parkinsonian syndromes. 

PMID- 24291852
TI  - [Transcranial sonography of substantia nigra in patients with Parkinson's
      disease].
AB  - Recent advances in basic research toward neuroprotective strategies of
      Parkinson's disease (PD) are increasingly highlighting the need for early
      diagnosis of PD. Substantia nigra (SN) hyperechogenicity, as visualized by
      transcranial sonography, has been heralded as a particularly useful diagnostic
      marker, as it is stable and remains unchanged with advancing stages of PD. In
      addition, SN hyperechogenicity is observable in patients in the very early stage,
      or even premorbid stages of PD. Prior studies have shown that SN
      hyperechogenicity is observable in approximately 90% of patients with PD and up
      to 10% of healthy controls. It has been hypothetically proposed that may be a
      vulnerability marker for nigrostriatal dopamine neuronds and may be related to an
      increase in iron content. It is expected that transcranial sonography of SN will
      be a feasible method for more accurate diagnosis of PD. 

PMID- 24291853
TI  - [Alpha-synuclein as a biomarker for early diagnosis of Parkinsonism].
AB  - Although alpha-synuclein protein (alphaS) aggregates from a monomer to assemblies
      such as oligomer, protofibril and mature fibril, the early intermediate
      aggregate, that is, oligomer has been considered to be most toxic species in
      recent reports. While it was reported that alphaS concentration in cerebrospinal
      fluid was decreased significantly in the patients with Parkinson's disease (PD)
      and dementia with Lewy bodies, there were reports that alphaS oligomer
      concentration was elevated in cerebrospinal fluid of PD patients. Moreover, it
      was supposed that alphaS oligomer concentration was also elevated in blood of PD
      patients. Further studies of alphaS in cerebrospinal fluid and blood would lead
      to establishment of the significance of alphaS as a biomarker for alpha
      synucleinopathies including PD. 

PMID- 24291854
TI  - [Thrombus formation and its embolic risk in atrial fibrillation].
AB  - Mural thrombus due to blood stasis develops in the left atrium as atrial
      fibrillation (AF) persists longer. Characteristically, its development depends on
      the endothelial function of the atrium, and the prevention and control of each
      component of CHADS2 score are thus important. Treatment of hypertension is
      essential in the primary prevention of AF, but once AF develops, its suppression
      will be the next step to address and catheter ablation is a useful intervention
      for this purpose. If these efforts fail, anticoagulation therapy for those with a
      substantial risk is mandatory. After the duration of AF and the bleeding risk are
      carefully taken into account, new oral anticoagulants with the risk of cerebral
      bleeding much less than warfarin are indicated. 

PMID- 24291855
TI  - [Cardioembolic stroke associated with atrial fibrillation].
AB  - Cardioembolic stroke is approximately 30% of brain infarction, and most of the
      embolus sources are atrial fibrillation (AF). Brain infarction with AF was
      associated with an elderly woman, main brain arterial occlusion, and large
      infarcts. Therefore, patient outcome is so sever, and mortality is very high
      compared with other stroke types. Use of the anticoagulant before stroke onset is
      only 32%, and less than 1.6 of PT-INR was 58.4%. The hospitalized recurrence was
      7.5%, which was not higher than stroke patients without AF. For detection of the
      intracardiac tthrombus, transesophageal cardiac-echogram detected thrombus in
      16.4%. Within five years after discharge, mortality rate was higher in stroke
      patients with AF than those without AF. Brain infarction with AF should be knock
      out stroke. 

PMID- 24291856
TI  - [Evidence of novel oral anticoagulants (NOAC)].
AB  - Novel oral anticoagulants (NOAC) such as the direct thrombin inhibitor,
      dabigatran, and oral factor Xa inhibitors, rivaroxaban and apixaban, have
      recently approved for prevention of stroke in nonvalvular atrial fibrillation
      (NVAF). Phase III trials have compared each of these agents to warfarin.
      Dabigatran was more efficacious than warfarin in reducing the risk of stroke when
      given at a dose of 150 mg BID to patients with NVAF. Rivaroxaban 20 mg QD was
      superior to warfarin in on-treatment analysis. Apixaban 5 mg BID was also found
      to be superior to warfarin in reducing stroke in NVAF patients. Of note, the rate
      of hemorrhagic stroke was much smaller in the patients treated with NOAC than
      those with warfarin. NOAC offer a good therapeutic option for prevention of
      stroke in NVAF patients. 

PMID- 24291857
TI  - [How to properly use warfarin and new anticoagulants].
AB  - Warfarin has unmet medical needs such as blood coagulation monitoring, limitation
      of vitamin K intake, and interaction with other drugs, while novel oral
      anticoagulants (NOACs) do not have such kind of unmet medical needs. Therefore,
      NOACs are recommended to busy patients or patients far from hospitals, or who do
      not want to limit vitamin K or use many other drugs concomitantly. NOACs are also
      recommended to patients with low time in therapeutic range (TTR). NOACs are also
      recommended to warfarin-naive patients. Warfarin is recommended to patients with
      economical difficulty because it is much cheaper than NOACs. If needed, warfarin
      should be selected in patients with renal insufficiency or under hemodialysis
      because NOACs are contraindicated. New guidelines by the European Society of
      Cardiology recommend NOACs to low risk patients with CHA2DS2-VASc score 1, and
      also as the first line to those with CHA2DS2-VASc 2 or more. Finally, drug should
      be determined by patients' preference. Doctors should give adequate information
      helpful for patients' selection.

PMID- 24291858
TI  - [Prevention and treatment of major bleeding during anticoagulation].
AB  - To prevent major hemorrhage during anticoagulation, it is quite important to
      manage controllable risk factors such as hypertension, diabetes mellitus, smoking
      habit, and too much alcohol intake. It is also important to avoid dual
      antithrombotic therapy as long as possible, which increases severe bleeding
      events. For patients with major bleeding during anticoagulation, we should stop
      oral medication, stop bleeding by mechanical compression or surgical
      interventions, and maintain circulation blood volume and blood pressure by
      appropriate intravenous drip infusion. When intracranial hemorrhage happens,
      adequate treatment to suppress blood pressure should be provided. Administration
      of prothrombin complex concentrate (PCC) and vitamin K is effective for urgent
      reversal of anticoagulation by warfarin. The PCC may be also useful for that by
      novel oral anticoagulants. 

PMID- 24291859
TI  - [Present state of predictive genetic testing for neuromuscular diseases: an
      overview by a neurologist in a local hospital].
AB  - Genetic tests for asymptomatic persons, who have family members with hereditary
      neuromuscular diseases, should be done carefully by following strict rules. For
      example, an examinee should be given a clear plan for clinico-psychological and
      social support services in case of testing positive. It is very important to
      assess the potential impact of genetic test results, so the anticipatory guidance
      should be provided times without number.It is difficult for local hospitals
      however, to fulfill such conditions during a primary genetic counseling, as they
      have limited staff. Our hospital is a case in point, where just one neurologist,
      who is also a certified clinical geneticist, provides the counseling, with the
      help of nurses, and social workers.The availability of second and third level
      genetic counseling systems have made it possible for us to carry out primary
      counseling, and we make every effort to ensure that clients and patients can
      avail our services any time, and without any constraints.In my opinion, a
      comprehensive education system to train primary care physicians in genetic
      testing and primary genetic counseling would prove beneficial for a lot of
      clients and also reduce the burden on neurologists. 

PMID- 24291860
TI  - [Present condition and problem of presymptomatic genetic testing].
AB  - For neuromuscular disease the best diagnosis is by genetic testing. Genetic
      testing is very important, however, the influence which a positive result can
      have on a family is very considerable. It can affect the family's lifestyle a
      lot. For example presymptomatic and prenatal genetic testing may be necessary for
      the family's children when they become adults themselves. We did qualitative
      research with five people who received presymptomatic genetic testing because of
      a family member with familial amyloidic polyneropathy. Heredity problems had a
      big influence on their life and on family dynamics. In order to support
      hereditary disease patients and their families, it is important to make a system
      which all medical institutions can use to help them cooperate together and deal
      with the treatment of hereditary diseases.

PMID- 24291861
TI  - [Current status of predictive genetic testing in neurological diseases - from the
      stand point of genetic specialist].
AB  - Although genetic reserch in neurological diseases has been dramatically advanced,
      its application to clinical neurology is still limited. Given the increased
      awareness of genetic testing in neurological diseases such as spinocerebellar
      ataxia, patients and their relatives' requests for information is increasing. In
      this report, we provide a framework for assessing genetic risk of neurological
      diseases in at-risk relatives baesd on our experience in TMDU medical hospital.
      Reagrding asymptomatic individuals, there are concerns that prerictive testing
      may trigger some unexpected psychological responses, such as severe depression
      and anxiety. Thus we also conducted a questionnaire for neurologists about
      predictive genetic testing in their clinic. Thre obtained results contained the
      complexed difficulties which can be shared among broader communities of medical
      specialists. 

PMID- 24291862
TI  - [Cell replacement therapy for Parkinson's disease using iPS cells].
AB  - The aim of stem cell therapy for Parkinson's disease (PD) is to reconstruct local
      synapse formation and/or induce the release of dopamine and cytokines from
      grafted cells in the putamen. Fetal ventral-midbrain cells are reported to
      relieve the neurological symptoms of PD patients. However, not only embryonic
      stem cells (ESCs), but also induced pluripotent stem cells (iPSCs) are expected
      to provide an alternative donor cell population because of their capacity for
      self-renewal and pluripotency. A protocol to generate dopaminergic (DA) neurons
      from ESCs and iPSCs has been developed, and human ESCs were proven to function in
      the brain of rat and monkey PD models. The next step will be the isolation of DA
      neurons as a donor cell population for a safe and efficient transplantation. 

PMID- 24291863
TI  - [Current status and perspective on regenerative medicine for spinal cord injury
      using iPS cell].
AB  - Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya
      Yamanaka and Sir John Gurdon, there is an increasing interest in the iPS cells
      and reprogramming technologies in medical science. While iPS cells are expected
      to open new era providing enormous opportunities in the biomedical sciences in
      terms of cell therapies for regenerative medicine, safety-related concerns for
      iPS cell-based cell therapy should be resolved prior to the clinical application
      of iPS cells. In this symposium, the pre-clinical investigations of cell therapy
      for SCI using neural stem/progenitor cells derived from iPS cells, and their
      safety issues in vivo are outlined. 

PMID- 24291864
TI  - [Retinal cell therapy using iPS cells].

PMID- 24291865
TI  - [Stem cell therapy for ischemic stroke using iPS cells].
AB  - Recently, several stem cell-based approaches have been considered as a novel
      treatment for stroke, such as delivery of non neural stem cells, stimulation of
      endogenous neural stem cells, and transplantation of neural stem cells. Among
      them, transplantation of neural stem cells is thought to have an advantage for
      functional recovery through neuronal replacement rather than other mechanisms. We
      demonstrated that human iPS cells derived neural stem cells form functional
      neurons and improve recovery after grafting in stroke-damaged rodents without
      tumor formation. Here we discuss about the potential and clinical application of
      iPS cells for stroke therapy. 

PMID- 24291866
TI  - [ALS disease modeling and drug screening using patient-specific iPS cells].
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which
      motor neuron (MN) loss in the spinal cord leads to progressive paralysis and
      death. Cytosolic aggregations in ALS MNs are composed of Tar DNA-binding protein
      43 (TDP-43). Genetic analysis has identified more than twenty mutations of TDP-43
      in ALS cases. Although accumulating evidence provides several hypotheses of
      disease mechanism, it is still needed to discover effective cure for ALS. We
      aimed to reveal cellular phenotypes in ALS MNs for identifying a drug-screening
      target for ALS using patient-specific induced pluripotent stem cells (iPSCs). To
      generate patient-specific iPSCs, dermal fibroblasts were obtained by biopsy from
      ALS patients carrying mutant TDP-43. The fibroblasts were reprogrammed by
      retrovirus or episomal vectors. Disease-specific iPSCs were differentiated into
      MNs expressing HB9 and SMI-32. Despite short culture period, ALS MNs
      recapitulated several disease phenotypes including detergent-insoluble TDP-43,
      shortened neurites and cellular vulnerability that observed in patient and animal
      models. Anacardic acid treatment reverted those phenotypes. Disease-specific
      iPSCs might provide a first step for drug-screening platform for ALS using
      patient-specific iPSCs. 

PMID- 24291867
TI  - [Clinical aspects of corticobasal syndrome].
AB  - Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder
      characterized by neuronal and glial accumulation of abnormal tau protein. The
      core characteristic clinical features of the disorder include progressive
      asymmetric akinetic-rigid syndrome with apraxia. Pathological examinations of
      patients presenting such clinical presentations have indicated that several
      proteinopathies, including tauopathies, amyloidopathies, TDP-opathies, alpha
      synucleinopathies, and prionopathies may underlie the same clinical phenotype.
      Because of this considerable clinicopathologic heterogeneity, experts use the
      term corticobasal syndrome (CBS) for patients with a clinical diagnosis of CBD,
      and reserve CBD for those whose conditions have been diagnosed on the basis of
      neuropathological analyses. In this review, we have focused on the clinical
      aspects of CBS, including its clinical presentation, diagnostic criteria, and
      pathological backgrounds. 

PMID- 24291868
TI  - [Genetic background of corticobasal syndrome].
AB  - Corticobasal syndrome (CBS) is associated with different pathologies including
      FTLD-tau (corticobasal degeneration; CBD, progressive supranuclear palsy, and
      Pick disease), FTLD-TDP, Alzheimer disease, Creutzfeldt-Jakob disease, and
      Parkinson disease/dementia with Lewy bodies. Genetic causes of CBS are also
      various reflecting diverse pathology. In familial and sporadic FTLD, MAPT, GRN
      and C9ORF72 mutations are three major causes of the disease. A part of patients
      harboring these mutations could exhibit CBS. In addition, the patients with
      TARDBP, FUS, LRRK2 or CSF1R mutations also have potential to exhibit CBS. In
      sporadic cases, H1 haplotype of MAPT is known to be associated with FTLD-tau,
      including CBS/CBD. Despite major advances in recent years, the majority of
      familial and sporadic CBS cases are genetically unsolved. In particular, little
      is known about both familial and sporadic cases of CBS in Japanese. Further
      studies are needed to unveil the genetic background of CBS. 

PMID- 24291869
TI  - [Neuroimaging in corticobasal syndrome].
AB  - Recently, several attempts have been made to characterize clinical symptoms and
      brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and
      corticobasal syndrome (CBS). Voxel-based morphometry (VBM) analysis of MRI
      revealed that frontal lobe involvement is characteristic of CBD. CBS was
      associated with perirolandic atrophy irrespective of underlying pathology. In CBS
      due to frontotemporal lobar degeneration (FTLD), atrophy extended into prefrontal
      cortex, striatum, and brainstem, whereas in CBS due to Alzheimer's disease (AD),
      atrophy extended into temporoparietal cortex and precuneus.No functional imaging
      study in pathology-proven CBD or CBS with known histopathology has been published
      today. PET and SPECT studies demonstrated that decreased glucose metabolism and
      cerebral blood flow in the fronto-parietal cortex, especially contralateral to
      the dominant symptoms in patients with CBS. [(18)F]6-fluorodopa PET and dopamine
      transporter SPECT studies demonstrated dysfunction of nigrostriatal dopaminergic
      function in CBS. A PET study showed decreased acetylcholinesterase activity
      (AChE) in the fronto-parietal cortex, and a correlation between cortical AChE
      activity and mini-mental state examination score in patients with CBS.Amyloid
      imaging agent is useful for detection of AD pathology in CBS. The recent
      development of tau imaging agent has made it possible to image distribution of
      neurofibrillary tangles in the brain in vivo. 

PMID- 24291870
TI  - [Differential diagnosis of corticobasal syndrome (CBS) and its biomarkers].
AB  - Corticobasal degeneration (CBD) was initially thought to represent a
      clinicopathological entity, but recent studies have shown its considerable
      clinicopathological heterogeneity. Thus, the constellation of the findings
      initially considered characteristic of CBD is now named "corticobasal syndrome"
      (CBS), while the term "CBD" is used for the histopathological disorder. Multiple
      phenotypes associated with CBD pathology and multiple diseases associated with
      CBS, the latter of which are called "CBD mimickers," make the correct diagnosis
      of these conditions on the basis of only clinical symptoms and signs difficult.
      Therefore, the development of specific biomarkers for diagnosing each causative
      disease of CBS is extremely important. Abnormal accumulations of the microtubule
      associated tau protein are found in both neurons and glia, and CBD is thus
      considered one of the tauopathies. Although some studies have measured total and
      phosphorylated tau in the CSF of patients with CBS, their results are
      inconclusive. Disease-specific truncation and/or phosphorylation of tau protein
      and its fragments in the CSF would be a promising biomarker candidate; however,
      its effectiveness still needs to be confirmed by further studies. Progress in
      biomarker development to differentiate CBD from CBD mimickers has been slow, but
      it is essential to improve diagnostic accuracy and to develop disease-modifying
      therapies. 

PMID- 24291871
TI  - [Development of therapies for Alzheimer's disease based on cholinergic hypothesis
      status quo and future directions].
AB  - Numerous approaches have been explored to treat individuals with Alzheimer's
      disease (AD). General approaches include the following treatment; treatment of
      cognitive symptoms, slowing decline, delaying onset of disease, and primary
      prevention. 2011 is the new era for the drug therapy for AD in Japan, because
      three anti-dementia drugs, galantamine, rivastigmine and memantine, were admitted
      to use for AD in addition to donepezil. Donepezil, galantamine and rivastigmine
      has been developed based on cholinergic hypothesis that acetylcholine (ACh) acts
      a chief neurotransmitter as a cognitive neurotransmitter. Donepezil a specific
      acetylcholinesterase inhibitor (AChEI). Galantamine acts as an allosteric
      potentiating ligand of nicotinic acetylcholine receptors in addition to the
      function of AChEI. Rivastigmine increase acetylcholine in the cholinergic synapse
      by inhibition of both AChE and butyrylcholinesterase. Recent study shows that
      these anti-dementia drugs afford symptomatic effect and also act as disease
      modifiers which inhibit neuronal death and abnormal amyloid-beta deposition.
      These effects can slow the rate of decline of the disease. While in the past many
      of our attempts have been to treat secondary symptoms or improve the cognitive
      deficits, future attempts are likely to focus on slowing the rate of decline,
      delaying the onset of appearance, or preventing the disease. 

PMID- 24291872
TI  - [Current status and perspectives on the development of AD therapeutics based on
      amyloid cascade hypothesis].

PMID- 24291873
TI  - [Present and future of the tau dementia therapy].
AB  - Neurofibrillarly tangles (NFTs) are seen most patients, who shows dementia, while
      beta amyloid deposition observed specifically in AD patients. NFTs observe first
      from coeruleus and entorhinal cortex, and then spread to neocortex, which well
      explain clinical progression of AD, such as memory problem to dementia. Tau
      fibrils are the major component of NFT. Before forming tau fibrils, tau binds
      together, form soluble tau oligomer, and then granular tau oligomer. The soluble
      tau oligomer associates with synapse loss, and granular tau formation induces
      neuronal loss. Therefore, tau aggregation inhibitor is expected to halt the
      clinical progression of AD. 

PMID- 24291874
TI  - [Oxidative stress hypothesis for Alzheimer's disease and its potential
      therapeutic implications].
AB  - Significantly increased levels of oxidized nucleic acids, proteins, and lipids
      have been described in the brains of subjects with Alzheimer disease (AD) and
      mild cognitive impairment (MCI) as well as young adults with Down syndrome,
      compared to age-matched controls. Therefore, it is speculated that oxidative
      stress (OS) and consequent cellular damage occur at an early-stage in the
      pathological cascade of AD. Until now, several antioxidants, mitochondrial
      protective agents, anti-inflammatory agents and metal chelators have been tested
      as possible OS-targeting therapeutics for AD. Although some of these agents have
      shown significant neuroprotective effects in cellular and animal models of AD,
      their efficacies in AD clinical trials have not been fully established. When
      limited efficacies of exogenous antioxidants in previous trials are taken into
      account, early-stage interventions aimed to activate endogenous antioxidants may
      be promising as OS-targeting therapeutic strategies for AD. A recent randomized
      controlled trial of dietary intervention for amnestic MCI is a good example of
      such an approach, where an OS-marker in cerebrospinal fluid is decreased and
      cognitive function is successfully improved by a diet with low-saturated fat and
      low-glycemic index. Indeed, transcriptional activators of endogenous antioxidants
      should be researched and tested in future clinical trials for AD. 

PMID- 24291875
TI  - [Update rehabilitation therapy for Parkinson disease].
AB  - Rehabilitation is essential for treatment of Parkinson's disease. New
      rehabilitation therapy is updated, in addition to evidence shown with
      "Parkinson's disease treatment guidelines 2011". Furthermore, a portable gait
      rhythmogram (acceleration sensor) is presented (not publication). Parkinsonian
      gait was significantly slow and the steps were small, but the cadence was not
      different compared as that of normal control. The strength of parkinsonian gait
      was apparently week compared as normal control. We also could examine consecutive
      changes of gait rhythm and detect freezing gait in patients. In this study, we
      could extract the characteristic of the parkinsonian gait and evaluate especially
      freeing events more objectively. This method may bring us to evaluate severity of
      parkinsonian gait not only in a consulting room but also daily profile even not
      to see directly, using the portable gait rhythmogram. 

PMID- 24291876
TI  - [Repetitive transcranial magnetic stimulation (rTMS) therapy for Parkinson
      disease].
AB  - In repetitive transcranial magnetic stimulation (rTMS), repetitive cortical
      stimulation induces after-effects, and rTMS has been applied as a treatment for
      various neurological or psychiatric disorders. Animal studies demonstrated that
      cortical stimulation could improve Parkinsonism, and a meta-analysis of clinical
      studies showed efficacy of high frequency rTMS. We conducted two clinical trials
      of supplementary motor area rTMS therapy for Parkinson's disease, and reported
      long-lasting efficacy. Other studies targeted specified aspects of Parkinson's
      disease, or utilized newly developed stimulation protocols. rTMS therapy for PD
      is a promising area, and can be an important treatment option in the near future.

PMID- 24291877
TI  - [DBS therapy for Parkinson's disease - our approach].
AB  - It is controversial whether the STN or the GPi, the main targets of DBS therapy
      in patients with Parkinson's disease, is the appropriate target. We select GPi
      DBS in patients judged by our cognitive function test battery to be at high-risk
      for cognitive decline after STN-DBS. While DBS surgery is usually performed under
      local anesthesia for the precise placement of DBS electrodes, general anesthesia
      might be useful in patients intolerant of long-lasting surgical stress. Our
      monkey experiments revealed that the most medial part of the STN receives direct
      input from the limbic cortex, suggesting that the spread of stimulation to these
      limbic territories may elicit adverse emotional effects. Other monkey experiments
      on the physiological mechanism of DBS suggest that high-frequency GPi stimulation
      disrupts information flow through the GPi. 

PMID- 24291878
TI  - [Problem of alternative medicine in Parkinson's disease].
AB  - I asked about the usage of alternative medicine to 300 outpatients with
      Parkinson's disease. 163 patients (54.3%) had experience with health appliance
      and 128 patients (42.7%) had experience with supplements. There is no health
      appliance or supplement whose efficacy for Parkinson's disease is approved
      publicly. Most of the patients understood it but some patients who purchased the
      goods believed to be effective in Parkinson's disease. In addition some patients
      feel affected because the purchase price is abnormally high. Continuous usage
      rate is generally high in supplements, relatively high in massage machine, but
      significantly low in equipment to move the body, such as muscle training
      equipment of various types or exercise bike. It seems important to inform this
      fact to Parkinson's disease patients. 

PMID- 24291880
TI  - [Clinical spectrum of anti-glycine receptor antibody-associated disease].
AB  - Anti-glycine receptor (anti-GlyR) antibodies were first reported in 2008 in a
      case of progressive encephalomyelitis with myoclonus and rigidity (PERM), which
      is a variant of stiff-person syndrome (SPS). After that, the antibodies have been
      studied extensively. At least 40 patients have been reported or presented until
      May 2013. We reviewed 28 patients (median age 47 years, range 1 to 75 years),
      whose clinical data are available. Seventeen patients (60%) were male. We
      classified clinical phenotype into PERM (17), classic SPS (5), variant SPS (5),
      and others (1: progressive optic atrophy). Nine patients (32%) had ant-GAD
      antibodies. Accompanied diseases included thyroiditis (5), diabetes mellitus (3),
      thymoma (3), and Addison's disease (2). Twenty-one patients (75%) treated with
      immunotherapy or thymectomy improved, but two of six patients without
      immunotherapy died or developed cardiac arrest. The clinical features suggested
      that antibody-mediated inhibition of the GlyR on the brainstem nuclei or spinal
      inhibitory interneurons may cause continuous firing of alpha motor neurons and
      paroxysmal excessive response to a variety of afferent impulses, leading to
      increased stiffness, brainstem signs, trismus, myoclonus, painful spasms or
      hyperekplexia. Phenotype associated with the anti-GlyR antibodies may be broader
      than previously thought, but among those PERM is the most common phenotype. 

PMID- 24291879
TI  - [Autoimmune encephalitis and its related-disorders].
AB  - Over the last few years, various autoantibodies against cell surface or
      intracellular antigens were identified in association with several forms of
      encephalitis, i.e. autoimmune encephalitis. Immunoprecipitaion and sequence
      analysis of the target protein (proteomics) provided the identification of the
      antigens corresponding to autoantibodies in autoimmune encephalitis. Appropriate
      preparation of antigens (synthesized peptides, or recombinant proteins prepared
      in E.coli or cultured mammalian cells) and assay systems (immunoblot, ELISA,
      immunoprecipitation or cell-based assay) should be selected for detection of each
      autoantibodies.Limbic encephalitis characterized by psychosis, dementia, seizures
      and abnormal movements is a common form of autoimmune encephalitis.
      Autoantibodies against the NMDA receptor, the AMPA receptor or the VGKC complex
      (LGI1 and Caspr2) were identified in limbic encephalitis with or without tumor
      association. Especially, limbic encephalitis associated with anti-NMDA receptor
      and ovarian teratoma became a distinct neurologic disorder to date.The
      intracellular antigens are also involved in several forms of encephalitis.
      Cerebellar ataxia is a common form of autoimmune encephalitis (cerebellits). The
      autoimmune cerebellar ataxia consists of paraneoplastic ataxia (anti-Yo etc.),
      anti-GAD-autoantibodies associated ataxia, gluten ataxia (anti-gliadin) and
      ataxic form of Hashimoto's encephalitis (anti-NAE).The early and accurate
      diagnosis of autoimmune encephalitis is important because most patients show
      responses to immunotherapy. 

PMID- 24291881
TI  - [Isaacs's syndrome and associated diseases].
AB  - Isaacs' syndrome is an antibody-mediated potassium channel disorder. Clinical
      symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation
      following muscle contraction, and hyperhidrosis. Hyperexcitability of the
      peripheral nerve cause these symptoms, which are relieved by administration of Na
      channel blockers and immunotherapy.The target channel proteins are voltage-gated
      potassium channels (VGKCs). The suppression of voltage-gated outward K(+) current
      by antibodies induces hyperexcitability of the peripheral nerve.
      Electrophysiological findings show that antibodies may not directly block the
      kinetics of VGKCs, but may decrease channel density. From the
      electrophysiological, pharmacologic and immunologic view points, the site of
      origin of spontaneous discharges is located principally in the distal portion of
      the motor nerve."VGKC antibodies" are also detected in Morvan syndrome (severe
      insomnia with neuromyotonia and various autonomic disorders) and in a form of
      autoimmune limbic encephalitis. Recent studies indicated that the "VGKC
      antibodies" are mainly directed toward associated proteins (for example LGI-1,
      CASPR-2) that complex with VGKCs themselves. The "VGKC antibodies" are now
      usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most
      common in limbic encephalitis with SIADH. CASPR-2 antibodies are present in the
      majority of patients with Morvan syndrome. 

PMID- 24291882
TI  - [Autoimmune autonomic ganglionopathy].
AB  - Autoimmune autonomic ganglionopathy (AAG) is a disorder of isolated autonomic
      failure associated with antibodies to the nitotinic acetylcholine receptor of the
      autonomic ganglia resulting in severe autonomic dysfunction. The disorder is
      associated with and most likely caused by antibodies to gAChR. In this study, we
      attempted to develop a novel technique to detect antibodies that bind to gAChR.
      We established a simple in vitro system termed GLIP (gaussia luciferase-reporter
      immunoprecipitation), which can detect protein-protein interactions with high
      sensitivity and using no radioisotope. Using this new method, we extensively
      reviewed the case histories with current clinical and laboratory evaluations that
      include testing for antibodies to p3 and 34 subunits of gAChR in serum available
      from the time of symptom onset. Here, we describe 7 patients with gAChR
      autoantibody and autonomic dysfunction. Our observations also suggest that
      autoimmune-mediated impairment of autonomic function may be partially reversible.
      Six of 7 patients improved in response to immunotherapy (e.g. PP, IVMP, IVIg, and
      immunosuppressant drugs) with symptomatic therapy. We interpreted the improvement
      in clinical symptoms correlated with the decrease in the levels of anti gAChR
      antibodies in each case. Some patients with seropositive AAG respond to treatment
      with IVMP or PP or IVIg, although when used as a single agent, subsequent
      treatments are required in patients to maintain the improvement. 

PMID- 24291883
TI  - [C9orf72 in Japanese amyotrophic lateral sclerosis (ALS)].
AB  - Recently, C9orf72 hexanucleotide (GGGGCC) repeat expansion in intron 1 was
      reported to be the most common cause of sporadic and familial amyotrophic lateral
      sclerosis (ALS)/frontotemporal dementia (FTD) in the Caucasian population. The
      frequency of the intronic repeat expansion is up to 21%-57% in familial ALS and
      3%-21% in sporadic ALS.In the Japanese population, the C9orf72 repeat expansion
      was found to account for 2.8% (3/109) of familial ALS, 0.4% (4/891) of sporadic
      ALS, and 0% (0/377) of normal healthy controls. Notably, among the Kii peninsula
      which has recorded a high incidence of ALS or ALS/PDC (parkinsonism-dementia
      complex), the frequency of the C9orf72 repeat expansion was 20% (3/15) indicating
      a high prevalence. All patients with the repeat expansion had a common risk
      haplotype within a narrower region than the Finnish one, suggesting a common
      founder effect which spread from Europe to East Asia in human migration
      history.Although Japanese ALS patients with the C9orf72 repeat expansion were
      rarer than Caucasian patients, we should check family histories of other
      neurological disorders such as dementia and FTD and should do genetic testing
      more actively even in sporadic ALS patients. Further studies of C9orf72 will
      clarify the pathogenesis and find the treatments for familial and sporadic ALS
      (or ALS/FTD). 

PMID- 24291884
TI  - [Molecular pathogenesis of ALS in TDP43 era].
AB  - To clarify the molecular pathogenesis of amyotrophic lateral sclerosis (ALS)
      associated with TAR-DNA binding protein 43 kDd (TDP-43), the quality and quantity
      of TDP-43 take a crucial role. Regarding to the quality of TDP-43, TDP-43 has
      been reported as an aggregate-prone protein. Especially the C-terminus of the TDP
      43 tends to form aggregate and has prion-like domain. Interestingly the mutations
      in the genes, which produce proteins with prion-like domain, have been identified
      in several neurodegenerative disorders. These results suggest the existence of
      the common property in the causative proteins for neurodegenerative disorders.
      For the quantity of TDP-43, the adequate amount of TDP-43 is necessary for
      maintaining cell function and cell survival. The amount of TDP-43 is tightly
      regulated by TDP-43. However the mechanism for autoregulation has not been fully
      elucidated. For the function of TDP-43, TDP-43 locates at stress granule, GEM and
      associates with the large genes and introns. Thus the alteration of TDP-43 may
      affect the function of stress granule, GEM and RNA metabolism in several genes.
      Moreover a U12 type spliceosome, which is matured in GEM, is decreased in ALS.
      The investigation of whether these dysfunctions explain the selective pathology
      in ALS provides a new therapeutic strategy for ALS. 

PMID- 24291885
TI  - [Amyotrophic lateral sclerosis (ALS) with the mutations in the fused in
      sarcoma/translocated in liposarcoma gene].
AB  - Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder
      characterized by the death of upper and lower motor neurons. Mutations in the
      fused in sarcoma/translated in liposarcoma (FUS/TLS) gene have been discovered to
      be associated with familial ALS. In a Japanese family with familial ALS, we found
      the R521C FUS/TLS mutation, which has been reported to be found in various ethnic
      backgrounds. The family history revealed 23 patients with ALS among 46 family
      members, suggesting a 100% penetrance rate. They developed muscle weakness at an
      average age of 35.3 years, and the average age of death was 37.2
      years.Neuropathological examination revealed remarkable atrophy of the brainstem
      tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons
      of the brainstem. We used immunohistochemistry to analyze 3 autopsy cases with
      the R521C mutation. As the disease duration becomes longer, there were broader
      distributions of neuronal and glial FUS/TLS-immunoreactive inclusions.

PMID- 24291886
TI  - [Dysfunction of dynactin 1 in motor neuron degeneration].
AB  - Dynactin 1 is an axon motor protein regulating retrograde transport of various
      proteins and vesicles including autophagosome. We previously demonstrated that
      the expression levels of dynacin 1 are markedly reduced in spinal motor neurons
      of sporadic ALS patients. We generated a Caenorhabditis elegans model in which
      the expression of dnc-1, the homolog of dynactin 1, is specifically knocked down
      in motor neurons. This model exhibited severe motor defects together with axonal
      and neuronal degeneration. We also observed the impaired movement and increased
      number of autophagosomes in the degenerated neurons. Furthermore, the combination
      of rapamycin, an activator of autophagy, and trichostatin which facilitates
      axonal transport dramatically ameliorated the motor phenotype and axonal
      degeneration of this model. Thus, our results suggest that decreased expression
      of dynactin 1 induces motor neuron degeneration and that the transport of
      autophagosomes is a novel and substantial therapeutic target for motor neuron
      degeneration. 

PMID- 24291887
TI  - [Cutting-edge MRI techniques for studying neurological diseases focusing on
      spinocerebellar degeneration].
AB  - This symposium discusses the utility of the different MR techniques in the
      diagnosis and management of spinocerebellar degeneration (SCD). Conventional MRI
      is widely used and can show characteristic signal abnormalities such as putaminal
      hyperintensity, hyperintense putaminal rim, putaminal hypointensity, hot cross
      bun sign in the pontine base, and hyperintensity in the middle cerebellar
      peduncles strengthening a diagnosis of multiple system atrophy (MSA). However,
      the diagnostic utility of these signal abnormalities in early MSA remains
      restricted. In addition, it should be considered that different magnetic field
      strengths and sequences could be influenced on the findings resulting false
      negative. On the other hand, proton magnetic resonance spectroscopy, diffusion
      weighted imaging (DWI), diffusion tensor imaging (DTI) and voxel based
      morphometry (VBM) in the pontine base, cerebellum, and putamen will be
      informative in the early diagnosis of MSA and other SCD prior to conventional MRI
      changes and even before any clinical manifestation of symptoms. Particularly,
      DWI, DTI, and VBM are expected to have potential as surrogate markers of disease
      progression. Further prospective and large studies including earlier disease
      stages will be needed to clarify whether these novel MR techniques will aid in
      the future sets of diagnostic criteria and therapeutic trials.

PMID- 24291888
TI  - [Principles of voxel-based morphometry and availability of integrated software
      BAAD].
AB  - BAAD is integrated software for investigation of brain morphological change using
      statistical parametric mapping (SPM). The basic part of the software is voxel
      based morphometry (VBM) that has been developed by Drs. Ashburner and Friston.
      Pathological changes with neuronal loss results in brain atrophy, which can be
      detected by MRI. VBM provides an automated and unbiased assessment of such
      morphometric change throughout the brain. Recently, VBM has been drastically
      improved by introducing the Diffeomorphic Anatomical Registration Through
      Exponentiated Lie algebra (DARTEL) registration method that implements a high
      dimensional warping process. BAAD supports the full-length steps for VBM analysis
      and makes it easy for everyone. BAAD is a free software and works on 64bit
      Windows machine without MATLAB installation.

PMID- 24291889
TI  - [Cutting-edge of advanced MRI for demyelinating diseases].
AB  - Demyelination shows different pathological changes spatially and temporarily, but
      conventional MRI cannot correctly demonstrate such pathological differences.
      Recently several advanced MRI techniques are introduced and especially
      magnetization transfer contrast, diffusion tensor imaging and MR spectroscopy are
      reported as the useful techniques to detect pathological and neurochemical
      differences on demyelinating diseases. By these newly-developed techniques, it
      may be possible to detect pathological and neurochemical changes on demyelinating
      diseases more correctly, leading to more appropriate therapy and correct
      prediction of patient's prognosis. 

PMID- 24291890
TI  - [MRI in epilepsy and migraine].
AB  - In vivo observation of the ictal events are thought to help understanding the
      etiology and pathology in both epilepsy and migraine. While simultaneous
      recording of EEG and fMRI is actively conducted for the former, in some cases,
      epileptogenic activity is undetectable by EEG. Attempts to detect such abnormal
      brain activity by using fMRI are underway. Analysis methods for resting-state
      fMRI can be applicable for such purposes. For migraine, fMRI is also highly
      valuable in detecting series of ictal events. However, since the disease is
      suspected to involve abnormal neuro-vascular coupling, it is not always
      straightforward how to interpret the observation by vascular-dependent methods.
      Therefore development of non-vascular methods is critical for future advances. 

PMID- 24291891
TI  - [In-vivo analysis for human brain maturation using MRI].
AB  - The evaluation of human brain maturation in vivo is a significant problem for
      pediatric neurologists. MRI, especially Diffusion Tensor Imaging (DTI) and (1)H
      MR Spectroscopy (MRS), can be a powerful method to solve this problem. A decrease
      in three eigenvalues (Deltalambda1 < Deltalambda2 ? Deltalambda3) and an increase
      in Fractional Anisotropy, as a function of brain maturation, was identified in
      the frontal and parietal white matter using DTI, which is a non-invasive imaging
      technique capable of providing a quantitative view of neural fibers and micro
      environmental alterations during the myelination period.MRS, a powerful technique
      capable non-invasively quantifying N-acetyl-aspartate (NAA), a marker for
      neurons, glutamate (Glu), an excitatory neurotransmitter, and creatine (Cr),
      revealed a decrease in the Glu/Cr ratio, but found no changes to the NAA/Cr ratio
      with maturational changes in brain networks, such as a decrease in cortical
      synaptic density (refinement).Therefore, we suggest these two MRI techniques, DTI
      and MRS, can be used to provide direct, non-invasive information on brain
      maturation in vivo, which we believe will help elucidate the pathophysiology
      behind neurodevelopmental disorders that disrupt normal brain maturation.

PMID- 24291892
TI  - [Alphalpha-dystroglycanopathy].

PMID- 24291893
TI  - [Myofibrillar myopaathy].
AB  - Myofibrillar myopathy (MFM) is a group of hereditary disorders pathologically
      characterized by focal disorganizations of myofibril structures with cytoplasmic
      inclusions. Most of the diseases so-called desmin-related or storage myopathy,
      cytoplasmic body myopathy, spheroid body myopathy, reducing body myopathy, and
      hyaline body myopathy are included in MFM. Several causative genes have been
      identified such as DES, CRYAB, MYOT, ZASP, BAG3, FLNC, DNAJB6, FHL1, TTN, and
      VCP. Most of these genes encode Z-line related proteins or proteins associated
      with protein quality control. Since MFM is the name from pathological
      characteristics, clinical features of the patients including the age at disease
      onset, affected muscles, disease course, and complications are quite variable. In
      this paper, characteristic clinical and pathological features of each causative
      gene are summarized. Unexpectedly, hereditary myopathy with early respiratory
      failure (HMERF) caused by mutation in the A-band region of TTN is the most common
      cause of MFM in our cohort. Despite of intensive mutation screening, the
      causative gene of more than 60% of MFM patients is still unknown. Further
      identification of novel causative genes and elucidate pathomechanisms of protein
      aggregation in necessary.

PMID- 24291894
TI  - [Myotonic dystrophy].
AB  - No effective treatment was available for myotonic dystrophy, even in animal
      model. We have established a new antisense oligonucleotide delivery to skeletal
      muscle of mice with bubble liposomes, and led to increased expression of chloride
      channel (CLCN1) protein and the amelioration of myotonia. In other experiments,
      we also identified small molecule compounds that correct aberrant splicing of
      Clcn1 gene. Manumycin A corrected aberrant splicing of Clcn1 in mouse model. 

PMID- 24291895
TI  - [New congenital muscular dystrophy due to CHKB mutations].
AB  - Congenital muscular dystrophy with mitochondrial structural abnormalities (MIM
      #602541), or also called megaconial congenital muscular dystrophy, is
      characterized clinically by early-onset muscle wasting and severe mental
      retardation, and pathologically by peculiar enlarged mitochondria that are
      prevalent toward the periphery of the fibers but are sparse in the center on
      muscle biopsy. Based upon the similarity in the pathological features to rmd
      mouse which has a recessive mutation in Chkb gene encoding the choline kinase
      beta that catalyzes first enzymatic step in a biosynthetic pathway for
      phosphatidylcholine, we have sequenced the CHKB gene in 15 patients with the
      disease and identified identified biallelic mutations in all patients. In muscle
      of three affected individuals with nonsense mutations, choline kinase activities
      were undetectable, and phosphatidylcholine levels were decreased while
      phosphatidylethanolamine levels were unchanged. Recombinant CHKB with identified
      missense mutations also showed reduced choline kinase activity, indicating that
      the disease is caused by the loss-of-function mutations in CHKB. Furthermore,
      mitochondria in the center of muscle fibers were subjected to autophagy on
      electron microscopy and these mitochondria did not have cytochrome c oxidase
      activity. The expression of parkin, PINK1, LC3, polyubiquitin, and p62 was
      upregulated in rmd muscles, indicating that mitochondria are eliminated by
      mitophagy. 

PMID- 24291896
TI  - [Clinical and histopathological features of myositis associated with anti
      mitochondrial antibodies].
AB  - Anti-mitochondrial antibodies (AMA) are known to be characteristic markers of
      primary biliary cirrhosis (PBC). The association of PBC with myositis has been
      reported mainly as case reports, and comprehensive studies of the clinical and
      histopathological features of patients with myositis and AMAs or PBC have not
      been conducted thus far. We retrospectively reviewed 212 patients with
      inflammatory myopathies in our laboratory and found 24 patients with AMA-positive
      myositis (11%) (seven patients with PBC and 17 patients without PBC). The
      analysis of clinical and histopathological features revealed that myositis
      associated with AMAs frequently include patients with a clinically chronic
      disease course, muscle atrophy, cardiopulmonary involvement and granulomatous
      inflammation, regardless of the presence or absence of PBC. We also reviewed and
      analyzed the clinical features of previously reported patients. The analysis of
      75 patients, which have been described in previous case reports including the
      ones of meeting abstracts, also showed the similar results about clinical
      features of myositis associated with AMAs and supported our findings. Our study
      suggests that myositis associated with AMAs form a characteristic subgroup. 

PMID- 24291897
TI  - [Immortalized adult rodent Schwann cells as useful tools for the study of
      peripheral nerve regeneration].
AB  - We have established spontaneously immortalized Schwann cell lines from adult ICR
      mice [IMS32] and Fischer344 rats [IFRS1]. IMS32 cells display distinct Schwann
      cell phenotypes such as a spindle-shaped morphology and the expression of glial
      cell markers (e.g. S100, glial fibrillary acidic protein (GFAP), p75 low-affinity
      neurotrophin receptor (p75(NTR))) and neurotrophic factors. In addition,
      conditioned medium obtained from IMS32 cells enhances neurite elongation of PC12
      cells and mouse dorsal root ganglion (DRG) neurons. IMS32 cells have been
      utilized to investigate the action mechanisms of various molecules that
      accelerate peripheral nerve regeneration (e.g. ciliary neurotrophic factor, sonic
      hedgehog, galectin-1). Like IMS32 cells, IFRS1 cells retain the characteristic
      features of mature Schwann cells as described above. Furthermore, IFRS1 cells
      have been shown to myelinate neurites in coculture with adult rat DRG neurons and
      PC12 cells. Our current investigation with IFRS1 cells focuses on the molecular
      mechanisms of myelination-inducible factors, such as soluble neuregulin-1 type
      III and exendin-4. These Schwann cell lines can be valuable tools for exploring
      neuron-Schwann cell interactions, pathobiology of axonal degeneration and
      regeneration in the peripheral nervous system, and novel therapeutic approaches
      against neurological disorders in patients with relevant diseases. 

PMID- 24291898
TI  - [Blood-nerve barrier and peripheral nerve regeneration].
AB  - Blood-nerve barrier (BNB) restricts the movement of soluble mediators and
      leukocytes from the blood contents to the peripheral nervous system (PNS)
      parenchyma and thus maintains the endoneurial homeostasis. However, it interferes
      the supply of various neurotrophic factors from the blood constituents and stops
      the drainage of toxic substances out of the PNS parenchyma, resulting in the
      inhibition of peripheral nerve regeneration. If the manipulation of BNB function
      is possible, regeneration of peripheral nerve may be facilitated via the
      alteration of peripheral nerve microenvironment and ample supply of neurotrophic
      substances. A possible method to manipulate the BNB for therapeutic purposes is
      to modify the endothelial function using siRNAs, oligonucleotides and virus
      vectors. Another possible method is to modify BNB pericytes: small hydrophobic
      substances that can reach the pericyte membrane through the endothelial monolayer
      and strengthen the pericytic activity, including the release of various
      cytokines/chemokines that influence endothelial function, may also be useful as
      drug candidates to control the BNB function. 

PMID- 24291899
TI  - [New horizon of treatments for peripheral nerve disorders].

PMID- 24291900
TI  - [Regenerative medicine of central and peripheral nervous system].

PMID- 24291901
TI  - [Recent pathophysiology of cluster headache (trigeminal autonomic cephalalgias;
      TACs)].
AB  - BACKGROUND: Cluster headache (CH), known as one of the trigeminal autonomic
      cephalalgias, is a stereotyped primary pain syndrome characterized by unilateral
      severe pain, the pathophysiology of which are not well understood.
      PATHOPHYSIOLOGY: The underlying pathophysiology of CH is incompletely understood.
      The periodicity of the attacks suggests the involvement of a biologic clock
      within the hypothalamus which controls circadian rhythms, with central
      disinhibition of the nociceptive and autonomic pathways, the trigeminal
      nociceptive pathways. Positron emission tomography and voxel-based morphometry
      have identified the posterior hypothalamic gray matter as the key area for the
      basic defect in CH. Functional hypothalamic dysfunction has been confirmed by
      abnormal metabolism based on the N-acetylaspartate neuronal marker in magnetic
      resonance spectroscopy. A recent case study demonstrated the release of both
      trigeminal and parasympathetic neuropeptides during a bout of pain in the same
      pattern previously described in CH. It is hypothesis that trigeminal activation
      leads to reflex autonomic activation. At a clinical level, there should be a pain
      threshold above which autonomic symptoms occur, modified by the highly somato-
      topic and functionally organized central connections of the trigeminovascular
      system.

PMID- 24291902
TI  - [Clinical profile of cluster headaches in Japan].
AB  - This study examined the clinical profile of cluster headache (CH) in Japan and
      the potential presence of features peculiar to Japan. Subjects comprised 110
      consecutive new CH patients (83 males, 27 females; mean age, 38.1 +/- 11.7
      years). While 85% of patients had visited other medical institutions, only 19%
      had received a correct diagnosis. Mean delay in diagnosis was 8.1 years. The
      common clinical features of the present report and previous Japanese reports were
      as follows: 1) a low prevalence of chronic CH; 2) a low prevalence of sense of
      restlessness; 3) an uncoupling of a sense of restlessness and restless behavior;
      4) approximately half of all patients experiencing CH attacks ranging in duration
      from 1-2 hours; 5) the location of CH most commonly reported as retro-orbital;
      and 6) lacrimation representing the most consistently reported autonomic feature.
      The common clinical features from 1) to 3) were seen in other East-Asia
      countries. Both frequencies of locations of CH and autonomic features differed
      between Caucasian and East-Asian populations. These characteristics may reflect
      ethnic and/or cultural differences between Eastern and Western CH patients. 

PMID- 24291903
TI  - [New treatments for cluster headache].
AB  - Subcutaneous injection and nasal spray of sumatriptan are known to be useful for
      the treatment of acute phase of cluster headache. Although nasal spry of
      zolmitriptan is not available in Japan, it is also reported to be effective for
      the acute phase of cluster headache. In addition, high flow oxygen is also
      reported to abort the attack of cluster headache. For preventive treatment of
      cluster headache, calcium channel blocker (verapamil) and steroids are
      recommended. In addition to these medications, some of refractory chronic cluster
      headache patients are reported to be respond to the occipital nerve block, deep
      brain stimulation, vagus nerve stimulation and occipital nerve stimulation.
      Furthermore, recent report revealed that stimulation of the sphenopalatine
      ganglion is effective for acute pain relief and attack prevention. This review
      will introduce the recent treatment for cluster headache including these nerve
      stimulations. 

PMID- 24291904
TI  - [Therapeuetic aspects of cluster headache in the practical clinical site].
AB  - The therapeutic procedures of cluster headache begin from the precise diagnose.
      Because cluster headache is usually accompanied with teeth pain and/or neck pain,
      some patients aren't able to consult adequate medical institutions. In this
      lecture I showed the some male and female patients as examples. The female
      patient was suffered from menstruation related migraine in her period of cluster
      headache. From the view point of treatment, preventive medicines are essential.
      They not just reduce severity and also improve the length of headache-period.
      Suitable preventive medicines may avoid the whole severe attacks. We reported
      therapeutic experiences of valproate, gabapentin and amitriptyline with verapamil
      in 2010 at general meeting of Societas Neurologica Japonica. Steroids are not
      indispensable. As for triptans rapid-type one are usually used. If the attacks
      are severe, sumatriptan subcutaneous injection kit (SSI) needs to be introduced.
      The expert nurses who are skilled in the procedures of SSI improve both patients'
      adherence and therapeutic efficiency. We held a first educational meeting of SSI
      in Tokyo 2012. Because cluster headache is formidable, the integrated therapy
      which is composed of precise diagnosis, preventive medicine and adequate
      medicines for headache attacks is essential and needed. 

PMID- 24291905
TI  - [International accreditation of medical school towards quality assurance of
      medical education].
AB  - An internationalization of practical medicine evoked international migrations of
      medical professionals. Since basic medical education is different among
      countries, the internationalization required international quality assurance of
      medical education. Global trend moves toward establishment of international
      accreditation system based on international standards. The World Federation for
      Medical Education proposed Global Standards for Quality Improvement as the
      international standards. Medical schools in Japan have started to establish
      program evaluation system. The standards which incorporated international
      standards have been published. The system for accreditation is being considered.
      An accreditation body, Japan Accreditation Council for Medical Education, is
      under construction. The accreditation is expected to enhance quality of education
      in Japan. 

PMID- 24291906
TI  - [Update on postgraduate clinical training].
AB  - It has been eight years since the postgraduate clinical training system was
      implemented in Japan. This training system is now being reviewed. Some issues on
      learning objectives and training programs have been pointed out. Outcome-based
      clinical training is necessary to assure quality of the postgraduate clinical
      training system and to achieve accountability to the society. Learning objectives
      should be redefined as competencies and authentic assessments like a workplace
      based assessment of mini-CEX should be implemented to improve this system. 

PMID- 24291907
TI  - [Renovation of medical specialty education system in Japan (current status and
      future perspectives)].
AB  - In order to further improve competences of specialized physicians and to correct
      uneven distribution of young physicians in Japan, Ministry of Health, Labour and
      Welfare has compiled a report on April 22, proposing major renovation of training
      system for specialized medical doctors. In the proposed system, there will be 19
      fundamental training areas for specialties, including general internal medicine,
      just after the completion of two-years of mandatory postgraduate clinical
      training defined by law. Japanese Board of Medical Specialties (tentative name),
      which is similar to ACGME in US, will be established as an independent
      organization in the late 2013 and play a pivotal role in renewal of the system.
      The new organization will possess two major functions, one is to assess and
      accredit training programs for medical specialties, and the other is to manage
      board examination systems for medical specialties. Specialty training based on
      the new system will commence in April 2017 at the earliest. In such
      circumstances, Japanese Society of Neurology will be requested not only to
      clarify competency profiles of capable neurologists but also to present effective
      training programs to produce such competent neurologists. 

PMID- 24291908
TI  - [Graduate medical education for neurology in Japan].
AB  - In Japan, the reconstruction of medical board certification system is under way.
      We have to show clearly to our people what is the specialty of neurology, and
      what professionals of neurology can do for them, For medical graduates who intend
      to become a professional of neurology in Japan, it is a prerequisite to obtain
      first the certification of general medicine under the newly developed board
      certification system. Therefore, we have to design our own effective education
      system of neurology, in collaboration with general medicine. We are also asked to
      determine by ourselves the adequate number of professionals of neurology, and to
      place them properly in each district throughout this country.In this short
      review, the present situation of the Japanese Society of Neurology in the coming
      medical board certification system and many issues to be solved are briefly
      discussed. 

PMID- 24291909
TI  - [Current status and problems in neurology education at graduate schools in
      Japan].

PMID- 24291910
TI  - [Earthquake and neurologists - role of neurologist as a primary care physician].

PMID- 24291911
TI  - [Management of patients receiving home respiratory care with tracheostomy and
      positive-pressure ventilation].
AB  - On March 11, 2011, the Great East Japan Earthquake occurred and a massive tsunami
      hit the northeastern coast of Japan. In Miyagi prefecture in Tokoku district, 49
      patients with amyotrophic lateral sclerosis were supported by home respiratory
      care with tracheostomy and positive-pressure ventilation at that time. Among
      them, two patients were died in the tsunami and 25 patients were forced to
      evacuate to hospitals. We should hurry to submit a guideline for medical
      transportation for patients with neuromuscular diseases requiring artificial
      ventilation. We also should research the disaster medicine in the field of
      neurology. 

PMID- 24291912
TI  - [Action proposals to Japanese Neurological Society from Fukushima Medical
      University: based on our three years' experiences].
AB  - In this paper, I make several proposals of what Japanese Neurological Society is
      able to do or should do in preparing future disaster in Japan. I mention several
      points separately.Patient education: Patients usually try to visit their hospital
      as soon as possible for the safety, especially in Japan. Is it true? The traffic
      jams actually blocked this action in March 11, 2011, which made more serious
      problems in some patients. We should ask them to prepare matters necessary for
      staying at home at least for a week when no medical emergency is present.Disaster
      prevention training: We should make a list of hospitals which accept emergent
      patients at disaster. We should have some methods of communication still active
      at disaster (internet, satellite phone) and make society network for
      communication and patient transportation. How to transfer required drugs to
      patients is another issue we should consider.Name tag: We sometimes treated
      unidentified patients in the disaster because the name tag or reference papers
      was gone or not specified to a certain patient. It is due to great mechanical
      power of injury or rains. For not detached from the patient and waterproofed, I
      recommend writing the patient's name on the chest with a permanent marker used in
      the triathlon when transferring the patients to other hospitals or other places. 

PMID- 24291913
TI  - [IT network establishment for neuropatients].
AB  - On March 11, 2011, big earthquake and subsequent gigantic tsunami killed more
      than 20,000 peoples in Tohoku area of Japan. Neurological patients were one such
      victim because they are usually very vulnerable to such a huge tragedy due to
      their physical disability including artificial ventilator-support. On occasion of
      the last tsunami, most cases showed "all or nothing" to lose life or to survive,
      and there were only a little cases who needed emergency surgical treatment. In
      the very early period, some neurological patients required electric power to keep
      their lifesupportive ventilator at evacuation house or even at home. In a week to
      a couple of months, many neurological patients needed continuous supply of their
      daily drugs which are essential to keep themselves in steady physical conditions
      and even for keeping their life.Japanese Neurological Society (JNS) began to
      establish an emergent assistant network system from January 2012 in an attempt of
      supplying materials, drugs and energy power to neurological patients who require
      both under a very early period after any natural or political disaster and a
      later period. For example, JNS is going to apply IT system to connect distant but
      safer hospitals which accept emergent patients from the center of disastrous
      place. JNS may also send emergency medical team to the disastrous place to save
      neurological patients by passing necessary medicine and materials or moving
      patients to safer hospitals. JNS will make such a tentative program public on our
      website to collect many other constructive opinions from general member of the
      society and neurological patients. After getting those opinions, JNS made up the
      exact team for this purpose after general meeting of JNS on this May 2012.Based
      on this team, disaster-mimic trial will be performed in Tokyo, Shizuoka, and
      Kochi where the next big disaster is going to hit the cities. 

PMID- 24291914
TI  - [Pathophysiology of brain injury and targets of treatment in acute ischemic
      stroke].
AB  - Brain is very vulnerable to ischemia, and exhibits various functional impairments
      in a flow-dependent manner. After onset of ischemia, the following cascade ensues
      propagating from the ischemic core to the surrounding area; ischemic
      depolarization, excitatory cellular injury induced by Ca(2+) and glutamate,
      oxidative injury induced by reactive oxygen species including various free
      radicals, secondary microcirculatory disturbance, edema formation, apoptosis and
      inflammation. Intrinsic protective responses are also activated at the periphery
      of ischemic area. From the clinical view point, urgent detection of "penumbra"
      area by imaging modalities such as diffusion-perfusion mismatch and rescuing this
      area from evolving into irreversible damage (infarction) are the most important
      issues. Therapeutic targets in the acute phase of cerebral infarction consist of
      vascular therapy including acute thrombolysis, prevention of microcirculatory
      disturbance, protection of blood brain barrier and promotion of collateral blood
      flow, and cellular therapy such as neuroprotective measures aiming at
      neurovascular unit. 

PMID- 24291915
TI  - [Intravenous rt-PA therapy: current status and extending therapeutic time window
      in Japan].
AB  - Several clinical studies carried out in Japan demonstrated that 0.6 mg/kg of
      intravenous alteplase within 3 hours of stroke onset could be safe and effective
      in routine clinical practice for Japanese patients. Since the approval, it has
      become the golden standard for acute ischemic stroke therapy, although there are
      huge gaps in frequency of use between various areas of Japan.Pooled analyses of
      randomized controlled trials in USA and Europe and the ECASS III clinical trial
      indicated the efficacy and safety of rt-PA therapy when expanding therapeutic
      time window (TTW) from 3 to 4.5 hours. The Japanese Government approved the 4.5
      hour time-window in August 2012, and the Japan Stroke Society published the 2nd
      version of guidelines of rt-PA therapy in October 2012. The author discussed on
      clinical implications of shortening the door-to-needle time and extending TTW of
      this therapy. 

PMID- 24291916
TI  - [Current status of endovascular therapy for acute ischemic stroke].
AB  - Endovascular therapy (EVT) is performed in patients with acute ischemic stroke
      due to major artery occlusion, if they were ineligible of intravenous (IV) rt-PA
      or failure to achieve reperfusion by IV rt-PA. In Japan, intra-arterial
      thrombolysis has been generally performed, and mechanical thrombectomy using
      Merci retriever and Penumbra system are gradually spreading. In 2013, the results
      of three randomized trials (IMS 3, SYNTHESIS expansion, and MR RESCUE) were
      published, and they could not prove the usefulness of EVT in patients with acute
      ischemic stroke compared with standard therapy including IV rt-PA. However, these
      trials suggested important issues of EVT. Especially, adequate selection of
      patients, improvement of reperfusion rate, and shorter onset to reperfusion time
      are needed to establish the usefulness of EVT. 

PMID- 24291917
TI  - [Brain protection against cerebral ischemia].
AB  - Previous clinical trials failed to show the benefit of several potentially
      protective drugs in acute ischemic stroke. However, there would be three main
      approaches for brain protection against stroke. The first is to develop a novel
      thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase
      and desmoteplase are in progress as a new thrombolytic drug. The second strategy
      is to augment collateral circulation through leptomeningeal anastomosis.
      Administration of G-CSF could enhance arteriogenesis, but it takes several days
      to develop functional collateral. For this purpose, partial aortic balloon
      clumping or stimulation of pterygopalatine ganglion may be promising. The third
      one is to protect neurovascular unit against reperfusion injury. Brain
      hypothermia is the most effective strategy in experimental ischemia, and the
      clinical trial for hypothermia combined with thrombolysis therapy is in progress.
      Activation of endogenous protective response, as presented by ischemic tolerance,
      has focused on remote ischemic conditioning. Although the precise mechanisms of
      remote preconditioning remain unclear, intermittent limb ischemia is a safe
      approach. Remote ischemic conditioning is now investigated in acute patients with
      thrombolysis therapy. 

PMID- 24291918
TI  - [Antiplatelet and anticoagulation therapy in acute cerebral infarction].
AB  - Effective treatments have recently been developed for acute cerebral infarction
      based on the pathophysiology.In atherothrombosis, artery-to-artery thrombosis
      plays a pivotal role in artery territory infarction and even in watershed
      infarction. In the latter, hemodynamic insufficiency is thought to prompt
      microembolism from the plaque in the area of borderzone of pial arteries. To
      suppress development of platelet thrombus on the ruptured plaque, strong
      antiplatelet therapy is required until the plaque stabilizes. Clinically dual
      antiplatelet therapy (DAPT) was reported to be more effective than mono therapy
      in suppressing microembolic signal in the middle cerebral artery. In addition,
      recent CHANCE trial reported that DAPT with aspirin and clopidogrel for the first
      21 days is more effective in suppressing stroke recurrence than aspirin alone.
      Risk of cerebral hemorrhage was not enhanced in the DAPT group. Short term DAPT
      in the acute phase may soon be a standard treatment for acute
      atherothrombosis.For prevention of cardioembolism in patients with atrial
      fibrillation, new oral anticoagulants (NOAC) have recently been introduced. In
      cases where risk of hemorrhagic transformation is minimal, immediate
      anticoagulation with NOAC may provide clinical benefit including prompt
      anticoagulant effect, no need for drug dosing, and low risk of intracerebral
      hemorrhage. 

PMID- 24291919
TI  - [Cell therapy for stroke].
AB  - Intravenous transplantation of mesenchymal stem cells (MSCs) derived from bone
      marrow has been reported to ameliorate functional deficits in several CNS
      diseases. The objectives of this presentation were to show feasibility and safety
      of cell therapy using auto serum-expanded autologous MSCs in stroke. Twelve (male
      and female) patients with stroke were enrolled. Cryopreserved MSCs were thawed
      and injected intravenously into patients over 30 min. Serial evaluations showed
      no severe adverse cell-related effects. In patients with cerebral infarcts, the
      intravenous administration of autologous MSCs appears to be feasible and safe,
      and merits further study as a therapy that may improve functional recovery. 

PMID- 24291920
TI  - [Rehabilitation for patients with cerebral infarction after transplantation of
      autologous human mesenchymal stem cells].
AB  - We participated as physiatrists in Honmou et al's study that designed to assess
      feasibility and safety of transplantation of autologous human mesenchymal stem
      cells in patients with cerebral infarction, and tried to detect improvements that
      were distinguishable from usual course of rehabilitation. Improvements of motor
      function were found in rather small functional units, such as movements in one of
      the fingers, toes, and a single joint of an extremity. In the methods of
      evaluation, Brunnstrom stage may detect gross changes, while the more detailed
      scales were necessary for assessment of recovery after transplantation of stem
      cells. In the investigator-initiated clinical trial of stem cell therapy for
      stroke, we are going to include fine-grained evaluation methods and investigate
      the most suitable technique of rehabilitation for patients after treatment. 

PMID- 24291921
TI  - [Olfactory mucosa autograft for chronic complete spinal cord injury].
AB  - The efficacy of olfactory mucosa autograft (OMA) for chronic spinal cord injury
      has been reported. New activity in response to voluntary effort has been
      documented by electromyography (EMG), but the emergence of motor evoked potential
      (MEP) reflecting electrophysiological conductivity in the central nervous system,
      including the corticospinal pathway after OMA has not been clarified. We report
      the emergence of MEPs after OMA. METHODS: Four patients, 3 men and 1 woman, were
      enrolled. The mean age of the cases was 30.3 +/- 9.5 years (range, 19 to 40
      years). All 4 cases were American Spinal Injury Association (ASISA) grade A. The
      mean duration from injury to OMA was 95. 8 +/- 68.2 months (range, 17 to 300
      months). Samples of olfactory mucosa were removed, cut into smaller pieces, and
      grafted into the sites of spinal cord lesions after laminectomy. Improvements in
      ASIA grade, variations in ASIA scores, EMG, SSEP, and improved urological
      function were evaluated as efficacy indicators. RESULTS: There were no serious
      adverse events in this series. In 2 of the 4 cases, an improvement in motor
      function below the level of injury was recognized. The emergence of MEP was
      recognized in the latter case at 96 weeks after surgery.

PMID- 24291922
TI  - [Basic strategy of rehabilitation for regeneration of spinal cord nerve].

PMID- 24291923
TI  - [Rapid identification of meningitis due to bacterial pathogens].
AB  - We constructed a new real-time PCR method to detect causative pathogens in
      cerebrospinal fluid (CSF) from patient due to bacterial meningitis. The eight
      pathogens targeted in the PCR are Streptococcus pneumoniae, Haemophilus
      influenzae, Streptococcus agalactiae, Staphylococcus aurues, Neisseria
      meningitides, Listeria monocytogenes, Esherichia coli, and Mycoplasma pneumoniae.
      The total time from DNA extraction from CSF to PCR analysis was 1.5 hour. The
      pathogens were detected in 72% of the CSF samples (n=115) by real-time PCR, but
      in only 48% by culture, although the microorganisms were completely concordant.
      The detection rate of pathogens with PCR was significantly better than that with
      cultures in patients with antibiotic administration.In conclusion, detection with
      real-time PCR is useful for rapidly identifying the causative pathogens of
      meningitis and for examining the clinical course of chemotherapy. 

PMID- 24291924
TI  - [Current advancement of the PCR-based molecular diagnosis for tuberculous
      meningitis].
AB  - Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis
      (TBM), is one of the severest forms of tuberculosis. At present, the diagnosis of
      CNS tuberculosis remains a complex issue because the most widely used
      conventional "gold standard" based on bacteriological detection methods, such as
      direct smear and culture identification, cannot rapidly detect Mycobacterium
      tuberculosis (M.Tb) bacilli in CSF specimens with sufficient sensitivity in the
      acute phase of TBM. Recently, instead of the conventional "gold standard", the
      various molecular-based methods, such as polymerase chain reaction (PCR) assay,
      has emerged as a promising new method for the diagnosis of TBM. Moreover, nested
      PCR assay has been reported as a key method that drastically increases the
      sensitivity and specificity of DNA amplification compared with conventional
      single-step PCR. Currently, a novel assay technique, which is internally
      controlled and combines the high sensitivity of nested PCR with the accurate
      quantification of real-time PCR, namely, Wide Range Quantitative Nested Real-time
      PCR (WR-QNRT-PCR) assay, has been developed. This novel assay technique is useful
      for the rapid diagnosis and the assessment of anti-tuberculosis treatment during
      clinical course of TBM. Therefore, in actual clinical practice, its wider use for
      diagnosis of TBM is expected in the future. 

PMID- 24291925
TI  - [Genetic diagnosis against fungal cerebromeningitis].
AB  - Fungal cerebromeningitis is one of deep seated mycoses and also a fatal fungal
      infectious disease. Regarding to causative pathogen of fungal cerebromeningitis
      in Japan, Cryptococcus spp., Candida spp., Aspergillus spp., are popular fungi.
      In general, the diagnosis of deep seated mycosis is sometime difficult. The
      genetic diagnosis method such as PCR against deep seated mycosis has been
      developing and it has been also reported as one of useful diagnostic tests.
      However, PCR for fungal detection is still a research test that has not been
      cleared or approved officially, therefore it should not be used for diagnosis, or
      patient management routinely. The PCR which detect broad range of fungi or
      specific fungus is applied for clinical situation, a careful attention should be
      paid for avoiding contamination because many fungal species are available in
      living environment. 

PMID- 24291926
TI  - [The diagnosis of toxoplasmic encephalitis by polymerase chain reaction].
AB  - The nested polymerase chain reaction (PCR) and the loop-mediated isothermal
      amplification (LAMP) assay were performed to detect and identify toxoplasma
      parasites in human cerebrospinal fluid (CSF). The performed nested PCR targeting
      the 18S rDNA using primers generated by Dr. L.D. Sibley instead of the
      conventionally used primers that target the B1 gene. Toxoplasma gondii-specific
      LAMP primers targeting both genes were also designed. The clinical sensitivity
      and specificity were evaluated using clinical CSF samples from 16 patients with
      toxoplasmic encephalitis (TE) and from 12 patients with other diseases. The 18S
      rDNA nested PCR showed the highest detection sensitivity limit with a minimum of
      1.0 * 10(-8) ng/MUl. However, sensitivity and specificity of nested PCR with
      clinical specimens were 50% and 100%, respectively. The sensitivity of molecular
      diagnosis of TE is not sufficient; therefore, patients clinically suspected of
      having TE should be treated promptly. This molecular diagnostic tool would
      restrictively facilitate a definitive diagnosis of TE at an early stage in
      approximately 50% of patients. 

PMID- 24291927
TI  - [History of hereditary motor and sensory neuropathy with proximal dominant
      involvement (HMSN-P)].
AB  - We established a new disease autosomal dominant hereditary motor and sensory
      neuropathy with proximal dominant involvement (HMSNP) in 1997, in Okinawa, Japan.
      This disease is characterized by proximal dominant neurogenic atrophy with
      fasciculations, painful muscle cramp, obvious sensory nerve involvement,
      areflexia, high incidence of elevated creatine kinase levels, hyperlipidemia and
      hyperglycemia. (MIM %604484). HMSNP is so called or HMSNO (HMSN OKINAWA type),.
      These clinical features resembled those of Kennedy-Alter-Sung syndrome. Most
      HMSNP patients have severe muscle atrophy and finally the tracheostomy and
      artificial ventilation are required. Therefore, we initially thought to classify
      HMSNP into a subtype of motor neuron disease (MND) like familial amyotrophic
      lateral sclerosis (FALS) or spinal muscular atrophy (SMA). However, the general
      consensus for MND was no sensory involvement. Therefore, as the disease showed
      severe sensory involvement, we categorized HMSNP in subtype of HMSN at that time.
      We also reported the pathology of HMSNP, showing severely decreased anterior horn
      cells, decreased posterior horn cells, and loss of posterior funiculus in the
      spinal cord. 

PMID- 24291928
TI  - [Pathomechanisms of motor neuron death by mutant TFG].
AB  - Mutations in TFG gene have been demonstrated in hereditary motor and sensory
      neuropathy with proximal dominant involvement (HMSN-P) and hereditary spastic
      paraplegia (HSP). A broad spectrum of TFG pathology is suspected in motor neuron
      diseases including amyotrophic lateral sclerosis (ALS). We performed mutation
      screening of TFG gene in ALS cases and evaluated the biological functions of
      mutant TFG by expression experiment in cultured cells. Two missense mutations
      associated with sporadic ALS were discovered. Mislocalization of ALS-related
      proteins, including TDP-43 and optineurin, was demonstrated. These results
      indicate that mistrafficking of ALS-related proteins by mutant TFG might be a
      biological cascade leading to motor neuron death. 

PMID- 24291929
TI  - [Neuropathology of proximal-dominant hereditary motor and sensory neuropathy
      (HMSN-P)].
AB  - Neuropathology of a case of Shiga pedigree with proximal-dominant hereditary
      motor and sensory neuropathy (HMSN-P) is reported. In the spinal cord, marked
      atrophy of anterior and posterior roots was found. Histologically, severe
      neuronal loss and gliosis were evident in the spinal anterior horns. Bunina
      bodies and hyaline inclusions were not seen. Neuronal loss and gliosis were mild
      in the hypoglossal and facial nuclei. Myelin pallor was evident in the posterior
      and lateral columns of the spinal cord. The posterior column, corticospinal tract
      and spinocerebellar tract showed loss of myelinated fibres and gliosis. In
      Clarke's nucleus, neuronal loss and gliosis were found. Dorsal root ganglion
      showed mild neuronal loss with a few Nageotte's nodules. In the precentral gyrus,
      mild loss of Betz cells and gliosis together with neurophagia were observed. In
      the iliopsoas muscle, islands of isolated muscle fibres can be seen against a
      background of fatty tissue. The sural nerve showed a markedly decreased number of
      large and small myelinated fibres without onion-bulb formation. Small infarctions
      were seen in the subcortical white matter, the basal ganglia, the brainstem and
      the cerebellum. Immunohistochemistry revealed ubiquitin-positive, TAR DNA-binding
      43 kDa-positive, TFG-positive inclusions in the remaining LMNs. 

PMID- 24291930
TI  - [Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN
      P) is caused by a mutation in TFG].
AB  - Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN
      P) is an autosomal dominant neurodegenerative disease characterized by proximal
      predominant weakness and muscle atrophy accompanied by distal sensory
      disturbance. Linkage analysis using 4 families identified a region on chromosome
      3 showing a LOD score exceeding 4. Further refinement of candidate region was
      performed by haplotype analysis using high-density SNP data, resulting in a
      minimum candidate region spanning 3.3 Mb. Exome analysis of an HMSN-P patient
      revealed a mutation (c.854C>T, p.Pro285Leu) in TRK-fused gene (TFG). The
      identical mutation was found in the four families, which cosegregated with the
      disease. The mutation was neither found in Japanese control subjects nor public
      databases. Detailed haplotype analysis suggested two independent origins of the
      mutation. These findings indicate that the mutation in TFG causes HMSN-P. 

PMID- 24291931
TI  - [Muscle ultrasonography: a new diagnostic tool for the diagnosis of ALS].
AB  - The diagnosis of amyotrophic lateral sclerosis (ALS) is frequently challenging,
      and needle EMG plays a central role to assess lower motor neuron dysfunction.
      Ultrasonography can clearly visualize fasciculation, one of characteristic
      features of ALS, and could contribute to the diagnosis of ALS. Echogenicity might
      be useful to assess chronic denervated changes of muscles, although there are
      some issues to be solved with regard to establishing methods and normal values.
      Attempts to utilize ultrasound to diagnose ALS have been just started. However,
      ultrasound has an advantage of non-invasiveness over EMG or nerve conduction
      study. Ultrasound could become a new tool to evaluate neuromuscular disease
      without pain in the near future. 

PMID- 24291932
TI  - [Ultrasonographic diagnosis of demyelinating neuropathy].
AB  - Ultrasonographic nerve enlargement has been reported in patients with
      demyelinating Charcot-Marie-Tooth disease, chronic inflammatory demyelinating
      polyneuropathy, multifocal motor neuropathy and POEMS (polyneuropathy,
      organomegaly, endocrinopathy, M protein, and skin changes) syndrome. Reference
      nerve sizes are needed at evaluation sites to determine nerve enlargement.
      However, neither site-based differences nor associations between the reference
      nerve sizes and several physical characteristics had been sufficiently verified.
      In our study, the reference nerve sizes of the median and ulnar nerves and the
      cervical nerve roots were determined in healthy Japanese adults. Site-based
      differences in the nerve sizes were observed. The stratification of reference
      nerve sizes according to gender is reasonable for practical use, as these
      differences reflect physical characteristics. The cross-sectional areas of the
      peripheral nerves were markedly larger at all evaluation sites in patients with
      demyelinating CMT than in patients with CIDP. However, the nerve sizes of the
      cervical nerve roots were not significantly different between patients with
      either disease. We also observed that the number of sites exhibiting nerve
      enlargement in the intermediate region of the median and ulnar nerves was useful
      to distinguish demyelinating CMT from CIDP. Thus, nerve ultrasonography is a
      promising diagnostic supportive tool for demyelinating neuropathy. 

PMID- 24291933
TI  - [Ultrasonography of muscle disease].
AB  - Muscle ultrasound is a useful tool of the neuromuscular disease. On muscle
      ultrasound, we can detect the affected muscle as increase of muscle echo
      intensity because of the fibrosis and fatty infiltration. Muscle atrophy and
      thickened muscle fascia are also visualized with muscle ultrasound. Another
      advantage of muscle ultrasound compared to other imaging technique is to
      visualize muscle movement, such as fasciculation. In this paper we review the
      findings of muscle ultrasound in normal muscle and affected muscle and discuss
      the possibilities and limitations of muscle ultrasound. 

PMID- 24291934
TI  - [Nerve ultrasound is useful for the diagnosis of neuromuscular diseases].
AB  - High-resolution ultrasound allowed for more detailed morphological assessment
      peripheral nerves and muscles. It is important to elucidate ultrasound features
      of peripheral nerves or muscles in various neuromuscular diseases because
      ultrasound is a widely used, non-invasive and easily accessible diagnostic tool.
      We attempted to demonstrate characteristic findings of nerve ultrasound in
      patients with Charcot-Marie-Tooth disease (CMT), Amyotrophic lateral sclerosis
      (ALS), and Cervical radiculopathy. In patients with CMT1A, cross sectional areas
      (CSAs) of all the nerves we examined were significantly larger than those in
      normal controls. Additionally, median nerve CSA had positive correlation with CMT
      neuropathy score, and negative correlation with nerve conduction velocity. In
      patients with ALS, increased CSA forearm/upper arm ratio of the median nerve was
      a characteristic finding to support the diagnosis. In patients with cervical
      radiculopathy, we could observe that decreased CSA and diameter of the nerve root
      corresponding to the findings of MRI and electromyography. These results
      demonstrate that the combination of electrophysiological study, diagnostic
      imaging, and nerve ultrasound could lead to accurate diagnosis of various
      neuromuscular diseases. 

PMID- 24291935
TI  - [Ultrasonography for the management of carpal tunnel syndrome].
AB  - Ultrasonography is useful for the management of carpal tunnel syndrome. It aids
      in the diagnosis of idiopathic cases, screening of local pathologies(space
      occupying lesions, tenosynovitis, and bone and joint abnormalities), incomplete
      release, and anatomic variations, and performance of low-invasive surgery. 

PMID- 24291936
TI  - [Pathophysiology of migraine chronification].
AB  - In approximately 3% of migraineurs, migraine evolves into more protracted and
      severe conditions annually. Meanwhile, approximately 26% of chronic migraine
      cases regain the episodic nature of migraine headaches in two years. The
      prevalence of chronic migraine is estimated to be approximately 1%. Although the
      pathophysiology of migraine chronification is poorly understood, several studies
      have demonstrated abnormalities in pain processing mechanisms. Of note, the
      descending pain inhibitory system has been found to be defective in chronic
      migraine patients. Topiramate appears to ameliorate the disease conditions by
      correcting such abnormalities in the pain processing mechanisms. Neurogenic
      inflammation around the dural trigeminal afferents is known to play an important
      role in the generation of migraine attacks. Botulinum neurotoxins inhibit
      regulated exocytosis at the nerve terminals by cleaving the SNARE protein,
      SNAP25. As a result, release of migraine-related neuropeptides, calcitonin gene
      related peptide and substance P, is reduced. Moreover, the insertion of transient
      receptor potential vanilloid subfamily, member 1 (TRPV1) into the plasma membrane
      is hindered by BoNT-A. We have demonstrated that the inability of TRPV1 to
      translocate to the plasma membrane results in its proteasome-mediated degradation
      within the trigeminal ganglion neurons, which may be relevant to the efficacy of
      BoNT-A against chronic migraine.

PMID- 24291937
TI  - [Current status of migraine chronification in Japan].
AB  - Chronification of migraine headache is one of the major issues to resolve
      urgently. The prevalence of chronic migraine is close to 2%, and the
      chronification occurs in approximately 2.5% of episodic cases annually.The
      pathophysiology of transformation from episodic to chronic migraine is still
      unclear. It is considered that there are several risk factors for migraine
      chronification; 1) non-modifiable: age, low education/socioeconomic status, and
      head injury, 2) modifiable: attack frequency, obesity, medication overuse,
      stressful life events, caffeine overuse, snoring, and other pain syndrome, 3)
      currently putative: allodynia, proinflammatory states, prothrombotic states, and
      specific genes.There were a few clinical reports concerning to the migraine
      transformation from abroad, but few data from Japan. The prevalence of chronic
      daily headache in our headache clinic in Japan was 20-30%. The medication overuse
      headache was the most prevalent form in the highest attack frequency (>15
      days/month) grope. Discontinuation of overused medication and administration of
      prophylactic medication were effective, and 40% of followed cases kept out of MOH
      at two years later.

PMID- 24291938
TI  - [Societal impact of migraine chronification].
AB  - Migraine is a common neurological disorder that produces substantial disability
      for sufferers. Chronic migraine (>= 15 headache days/month; CM) was significantly
      more disabling than episodic migraine (< 15 headache days/month; EM). CM was
      associated with greater impairment of occupational and social aspects of quality
      of life. Lost productivity time was substantially higher among CM participants
      than persons with EM. Full time employment was lower in CM participants because
      of medical leave. The medical costs were two or three times higher for CM than
      EM. These results suggest that migraine chronification is associated with
      substantial economic burden.

PMID- 24291939
TI  - [Management of chronic migraine in Japan].
AB  - The Japanese Headache Society and the Japanese Society of Neurology has published
      the 2013 guidelines for the diagnosis and treatment of chronic headache. A new CQ
      has been set up in the guidelines on the topic of "How to treat chronic
      migraine." In the past, lomerizine was the only prophylactic medication of
      migraine that was eligible under insurance coverage. However, afterward in 2010,
      valproate was added to the list of antimigraine medications approved under
      insurance coverage, followed by propranolol, amitriptyline, and verapamil, with
      rapid advances in the treatment of migraine. Valproate, topiramate (not approved
      under insurance coverage until date), and amitriptyline could potentially be used
      in the treatment of chronic migraine in Japan; further, considering the clinical
      outcomes thus far, lomerizine could also be added to the list. As a drug for
      migraine prophylaxis, valproate is contraindicated in pregnant women and needs to
      be used with caution. 

PMID- 24291940
TI  - [Localization in neuropsychology].
AB  - Cognitive impairment is a part of neurological findings. Localization of each
      cognitive function, however, is not as straightforward as motor or sensory
      functions. Individual differences in premorbid abilities and functional network,
      in addition to the hierarchical organization of cognitive functions, make
      functional localization highly complicated. Brain-behavior relationships have
      been studied in patients with focal lesions, such as cerebrovascular diseases or
      brain tumor. Nowadays, distribution of brain atrophy in relation to cognitive
      performance is also investigated in neurodegenerative disorders using various
      neuroimaging techniques. Neurologists can take the pathological processes in each
      disease into account when they explore the distribution of impaired neural
      networks. Integrating sophisticated lesion analysis with deficit analysis based
      on knowledge of normal cognitive function would clarify brain-behavior
      relationships. 

PMID- 24291941
TI  - [Neural correlates of memory].
AB  - Memory can be divided into several types, although all of them involve three
      successive processes: encoding, storage, and retrieval. In terms of the duration
      of retention, neurologists classify memory into immediate, recent, and remote
      memories, whereas psychologists classify memory into short-term and long-term
      memories. In terms of the content, episodic, semantic, and procedural memories
      are considered to be different types of memory. Furthermore, researchers on
      memory have proposed relatively new concepts of memory, i.e., working memory and
      prospective memory. This article first provides explanations for these several
      types of memory. Next, neuropsychological characteristics of amnesic syndrome are
      briefly outlined. Finally, how several different types of memory are affected (or
      preserved) in patients with amnesic syndrome is described. 

PMID- 24291942
TI  - [Aphasia--a new as well as old problem].
AB  - Alajouanine (1956) established a concept of jargon as a speech symptom of aphasia
      and gave clinical descriptions of three types of jargon-undifferentiated,
      asemantic (neologistic) and paraphasic (semantic) jargon. Several case-reports of
      undifferentiated jargon in Japanese language have been published in clinical
      aphasiology. On the other hand language development of jargon-type in normal
      children was reprorted in developmental psychology. We point out a
      phenomenological similarity of clinical language symptoms of jargon with language
      development of jargon-type considering its neuropsychological implications. 

PMID- 24291943
TI  - [Neuropsychology of consciousness].
AB  - The nature of the relation between neuropsychology and consciousness has become a
      major issue. DB had a left lower quadrant hemianopia. When questioned about his
      vision in the left lower field, DB reported that he saw nothing. When DB was
      asked to point to locations in the impaired field in which spots of light were
      turned on briefly, he was surprisingly accurate. Apparently, even though DB could
      not consciously perceive a light in his blind region, his brain knew where it had
      appeared. This phenomenon has become known as blindsight. DF suffered carbon
      monoxide poisoning. The result in DF was an extensive lesion of the lateral
      occipital region, including cortical tissue in the ventral visual pathway. The
      principal deficit that DF experienced was a severe inability to recognize
      objects, which is known as visual form agnosia. Despite her inability to identify
      objects or to estimate their size and orientation, DF still retained the capacity
      to appropriately shape her hand when reaching out to grasp something. The anoxic
      episode affected her vision for perception, but left her vision for action
      largely unscathed. These patients lack conscious awareness about some subset of
      information, even though he or she processes that information unconsciously. 

PMID- 24291945
TI  - [Clinical manifestations and epidemiology of prion diseases in Japan].
AB  - In Japan, prion diseases are classified into 76.6% with sporadic Creutzfeldt
      Jakob disease (sCJD), 19.6% with genetic prion diseases, and 4.9% with acquired
      prion disease. In sCJD, MM1 type sCJD, which show typical clinical course of CJD,
      is the most common. Among atypical sCJD cases, MM2 type sCJD is the most common.
      In genetic prion diseases, the most common mutation of prion protein gene is
      V180I. All cases with acquired prion diseases except for one case of variant CJD
      are dura mater graft-associated CJD (dCJD), and the number of dCJD in Japan is
      account for more than 60% of all patients with dCJD all over the world. The
      remarkable frequency of dura mater graft use in Japan might contribute to the
      elevated incidence of dCJD, but the possible reasons for the disproportionate use
      of this procedure in Japan remain unclear. Our recent study revealed that
      differences in the medical conditions precipitating dura mater graft might
      contribute to the frequent use of cadaveric dura mater and the higher incidence
      of dCJD in Japan.

PMID- 24291944
TI  - [Review of basic knowledge, surveillance and infectious control of prion
      disease].
AB  - Prion disease is developed by changing normal prion protein to transmissible
      abnormal prion protein and its accumulation in the brain. Drug development
      project using small chemical molecules is now progressing based on constitutional
      analysis of prion proteins, and a domestic network for clinical trial is
      consolidating. Prion disease is classified into 3 types, and the Japanese Prion
      Disease Surveillance Committee has identified 2,026 patients with prion diseases
      during 14 years from 1999 (sporadic: 77%, genetic: 19%, environmentally acquired:
      4%). Compare with patients in other countries, relatively larger amount of
      patients with dura mater graft-associated Creutzfeldt-Jakob disease (CJD) and
      genetic prion diseases have been characteristically identified. Sporadic
      classical CJD patients, which present rapid progressive dementia, are identified
      in most of the cases. Genetic prion disease are classified into 3 major
      phenotypes such as genetic CJD, Gerstmann-Straeussler-Scheinker disease (GSS)
      mainly showing spinocerebellar ataxia, and fatal familial insomunia. All the 83
      cases but 1 case of variant CJD were dura-grafted CJD in environmentally acquired
      prion disease. Accurate diagnosis and prevention of secondary infection are
      important according to those surveillance data and systems.

PMID- 24291946
TI  - [Neuroimaging in the differential diagnosis of prion disease].
AB  - MRI including diffusion-weighted imaging (DWI) and fluid-attenuated inversion
      recovery (FLAIR) is useful for the diagnosis of prion disease, particularly
      Creutzfeldt-Jakob disease (CJD). Hyperintensity lesions are predominant on DWI,
      and are often seen in the cerebral cortex ("cortical ribboning") or both in the
      cerebral cortex and striatum (anterior dominant). However, clinical and MRI
      findings of CJD can be mimicked by those of many other dementing conditions,
      including autoimmune encephalitis. Non-prion diagnosis should be considered when
      hyperintensity is predominant on FLAIR, apparent diffusion coefficient (ADC) is
      increased early, the lesion is symmetric, the limbic region is most affected, or
      ADC is decreased in the white matter.

PMID- 24291947
TI  - [CSF analysis of patients with prion disease by biomarkers and real-time qucking
      induced conversion (RT-QUIC) method].
AB  - Hsich et al reported 14-3-3 protein in CSF supports a diagnosis of human prion
      disease, and 14-3-3 protein is one of supportive diagnostic criteria on WHO
      (1998). In the presence of 14-3-3 protein and total tau protein is widely used as
      a surrogate marker in the pre-mortem diagnosis of human prion disease and other
      rapidly progressive dementia. Most recent research report that the sensitivity of
      14-3-3 protein was 43%-100%, and the specificity of 14-3-3 protein was 47%-97%.
      And the sensitivity of total tau protein was 43%-100%, and the specificity of
      total tau protein was 47%-97%. In other hand we recently developed a new in vitro
      amplification technology, designated "RT-QUIC assay", for the detection of
      PrP(Sc) in CSF of sCJD. Other group reported that CSF RT-QUIC method analysis has
      the potential to be a more specific diagnostic test for sCJD than current CSF
      tests, but their method is different from our method and their study was not
      enough. Now we are analyzing for the sensitivity and specificity of biomarkers
      and RT-QUIC method in CSF of definite cases of human prion disease, the number of
      definite cases of human prion disease is larger than that of other studies. 

PMID- 24291948
TI  - [Treatment for prion disease: recent progress].

PMID- 24291949
TI  - [Treatment of spasticity with botulinum toxin].
AB  - The beneficial effects of rehabilitation are known to plateau around 6 months
      after stroke. But there are some reports that motor functions are improved with
      using botulinum neurotoxin A (BoNT-A) for limb spasticity in the maintenance
      stage of stroke. Though it has been thought that BoNT-A works in the peripheral
      nerves so far, Caleo showed BoNT-A can affect the central nervous system. We
      suspected BoNT-A affected the spinal cord directly following retrograde
      transsynaptic transport from his reports. We deduce the abnormal stretch reflex
      is made a modification by affecting the spinal cord, and it follows that motor
      function.We suggest it is important BoNT-A injection immediately followed by
      intensive rehabilitation to regain active motor function, because BoNT-A has a
      specific affinity to cleave certain proteins involved in the mechanism of
      acetylcholine exocytosis. We propose BoNT-A treatment at 3-month interval should
      be set.

PMID- 24291950
TI  - [Spasticity must be treated by botulinum toxin with rehabilitaiton].
AB  - In rehabilitation medicine, botulinum toxin (BTX) as adjunct to other
      interventions for spasticity can result in a useful and effective therapeutic
      tool treating disabled stroke patients with spasticity. Other than spasticity,
      non-reflex motor disorders (muscle stiffness, shortness and contracture) can
      complicate clinical course and hamper rehabilitative process of stroke patients.
      After treating spasticity by BTX, the paralysis might be improved by changing
      muscular imbalance following stroke. We also have to face unique and difficult to
      treat clinical conditions abnormal posture and movement disorders due to chronic
      severe stroke patients. The effectiveness of BTX in treating some of these
      conditions is also provided. Since, neurologically disabled stroke patients can
      show complex dysfunction, prior to initiating BTX therapy, specific functional
      limitations, goals and expected outcomes of treatment should be evaluated and
      discussed with family and caregivers. BTX also might improve not only care,
      passive function, but also improve active function in stroke patients with
      intensive rehabilitation with rTMS, tDC, electrical stimulation, stretching and
      other rehabilitation strategy. Therefore BTX might change rehabilitation
      medicine.

PMID- 24291951
TI  - [Repetitive transcranial magnetic stimulation and rehabilitation].
AB  - NEURO (NovEl intervention Using Repetitive TMS and intensive Occupational
      therapy) have been recently reported to be clinically beneficial for post-stroke
      patients with upper limb hemiparesis. We confirmed the safety and feasibility of
      the protocol in 1,008 post-stroke patients from different institutions, and
      identify predictors of the clinical response to the treatment. And in our
      randomized controlled study of NEURO and constraint-induced movement therapy,
      NEURO showed the superiority of NEURO relative to constraint-induced movement
      therapy; NEURO improved the motion of the whole upper limb and resulted. We have
      investigated the recovery mechanism using electrophysiological examination and
      functional magnetic resonance imaging. Low-frequency rTMS applied to the non
      lesional hemisphere in post-stroke patients significantly decreased the F-wave
      frequency and amplitude in the affected upper limb, suggesting that this modality
      has an anti-spastic effect in post-stroke patients. Serial functional magnetic
      resonance imaging indicated that our proposed treatment can induce functional
      cortical reorganization, leading to motor functional recovery of the affected
      upper limb. Especially, it seems that neural activation in the lesional
      hemisphere plays an important role in such recovery in poststroke hemiparetic
      patients. 

PMID- 24291952
TI  - [Repetitive facilitative exercise: recent evidence and development for
      combination therapy].
AB  - Repetitive facilitative exercise (RFE), a combination of high-dose (high
      frequency) of repetitions and neurofacilitation, is a recently developed approach
      to the rehabilitation of stroke-related limb impairment. We conducted a
      randomized controlled evaluation of RFE compared with a duration-matched
      conventional rehabilitation program in the treatment of subacute stroke-related
      upper extremity impairment (Shimodozono et al. 2013). RFE demonstrated both
      statistically and clinically significant benefits over conventional
      rehabilitation both on the Action Research Arm Test, which is designed to measure
      dexterity and function, and on the Fugl-Meyer Arm scores, which was chosen as
      measure of motor control. In the case-series study, the beneficial effect of RFE
      is also reported in the treatment of chronic phase of stroke. More research is
      needed, but RFE could conceivably be integrated with other approaches such as
      vibration, neuromuscular electrical stimulation, repetitive transcranial magnetic
      stimulation, botulinum toxin, and robotics to achieve further improvement in its
      capabilities.

PMID- 24291953
TI  - [Clinical application of prism adaptation for patients with unilateral spatial
      neglect].
AB  - Unilateral spatial neglect (USN) is defined as a failure to pay attention to the
      contralesional space due to the brain damage. As this symptom affects on many
      aspect of activities of daily living, a lots of therapeutic approaches were
      developed so far. Among them, prism adaptation (PA) technique is one of the most
      promising methods because it could produce generalized and long lasting after
      effect and is effective even for chronic USN patients. It is, however, true that
      there are USN patients showing no PA effect. Unfortunately, we cannot tell in
      advance who can adapt to prisms and show improvement of their neglect symptom at
      this moment. In further studies, to know who is more likely to adapt to prisms we
      should analyze clinical data from USN patients showing improvement by PA. In
      addition, to be an effective PA technique for much more patients with USN we
      should clarify what it the best condition in PA task. 

PMID- 24291954
TI  - [Overview of involuntary movements].
AB  - This issue is a kind introduction for the next three speakers who will give
      lectures about three considerably pathophysiology-known involuntary movements:
      tremor, myoclonus and dystonia.What's involuntary movement? This question relies
      on what is a voluntary movement. Some movements may include voluntary components
      and involuntary components. It usually excludes normal reflex movements, but they
      are sometimes included in the involuntary when much enhanced and cause some
      problems for the patients.Classification of involuntary movements. Clinical
      classification is based on clinical features, and it is, therefore, the same as
      how we explain some unknown movements to others. The rhythmicity, rapidness,
      pattern, stereotypy, part of the body involved, trigger factors are main features
      we use.How to record them. Video recording is the best method to record and show
      them to others. EEG, evoked potentials, polygraphs and some other physiological
      studies may help you to analyze their pathophysiology. 

PMID- 24291955
TI  - [Pathophysiology in dystonia: functional anatomy of basal ganglia].
AB  - Clinical manifestation of dystonia features involuntary muscle contraction or
      spasm resulting in postural and movement disorders. Depending on the distribution
      and spreading pattern of dystonia, four patterns have been described, including
      focal, segmental, multifocal and generalized dystonia. Dystonia can be seen as
      one of additional clinical features in a more severe neurologic condition. Most
      of pathophysiology in dystonia remains to be elucidated. Considering the
      pathology in secondary dystonia, basal ganglia is mostly involved, especially
      putamen. Dysfunctions of the cerebello-thalamo-cortical loop would result in
      development of dystonia. Stereotactic and functional neurosurgery has been
      demonstrated to provide clinical benefits to dystonia patients. In addition,
      involvement of other neuronal circuit or tissue has been revealed, including
      cerebello-thalamo-cortical loop, brainstem, spinal cord and peripheral nervous
      system. Elucidation of pathophysiology, molecular genetics, and functional
      neuroanatomy would further contribute to developing therapeutic strategy in
      dystonia. 

PMID- 24291956
TI  - [Pathophysiology of tremor rhythm].
AB  - Tremor is a rhythmic involuntary movement of any body parts. Some peripheral and
      central mechanisms can produce it. The former includes peripheral mechanical
      oscillations and oscillations due to spinal reflexes. The latter includes central
      oscillations originated from some central pacemakers or network loops through
      cerebellum, basal ganglia or others.Weight loading on a body part is one method
      for differentiation between the peripheral and central mechanisms. In peripheral
      tremor, the weight load usually changes the tremor frequency. In contrast, it is
      not affected by the load in the central tremor. Both mechanisms relate to produce
      essential tremor and enhanced physiological tremor.Basal ganglia, sensory-motor
      cortex, cerebellum, red nucleus and inferior olive nucleus could be the central
      pacemakers or involved in the central loops for tremor.The facilitation and
      inhibition imbalance within a pacemaker or imbalance between feed-forward and
      feedback regulations within central loops may generate some rhythms. 

PMID- 24291957
TI  - [Pathophysiology of cortical myoclonus].
AB  - Myoclonus is one of the common movement disorders in clinical practice, and its
      differential diagnosis is important. Usually, myoclonus can be classified into
      cortical, subcortical, brain stem, spinal and peripheral, based on its
      pathogenesis. Especially, cortical myoclonus is closely associated with epilepsy
      (myoclonic epilepsy) and has been studied extensively so far. Here, we will
      review the pathogenesis of cortical myoclonus from the viewpoint of clinical
      neurophysiology. 

PMID- 24291958
TI  - [Future medical care for intractable diseases, general view].

PMID- 24291959
TI  - [The prospective program for intractable diseases].

PMID- 24291960
TI  - [Global strategy for rare and intractable diseases].
AB  - The progress has been made in research on rare and intractable diseases, for
      which new drug development has long been limited due to rarity, by establishing a
      global network in recent years. In Japan, the countermeasure of rare and
      intractable diseases has been implemented under national policy outline as an
      integrated strategy since 1972, including surveys and research, construction of
      medical facilities, reducing burden of medical expenses for patients, and
      enhancement of welfare and improving QOL of patients. Along with legislation or
      regulation of orphan drugs development, treatment and care for rare diseases have
      been emphasized in each national healthcare system globally. In the US, the
      Office of Rare Diseases was established under NIH in 1989 and European countries
      also started collaboration for rare disease projects with their own national
      plans in 1999. As a platform of rare diseases patients, healthcare professionals,
      researchers, pharmaceutical industry, and policy makers, Orphanet has a well
      designed website which networks them. In Japan, there are urgent needs for global
      standard patient registration system and strengthening global collaboration for
      developing treatment and care for the patients of rare and intractable diseases,
      which needs more cooperative relations with patient organizations and
      pharmaceutical industry within country. 

PMID- 24291961
TI  - [Medical treatment of NANBYO from patients' perspective].
AB  - NANBYO policy which has practiced since 1972 has been discussing for making
      fundamental reform. As a part of a plan to reform, "Total Supports for Persons
      with Disabilities Act" executed. The target of this act is included with NANBYO
      patients. Regarding to the enforcement of the act, there are major changes as
      follows; 1) Regional government has a responsibility to set up the support
      project for NANBYO patients, 2) Welfare policy will be altered by a change in the
      definition of disability (the target of welfare for the disabled is not only
      patients who have fixed disabilities but have changed (e.g. NANBYO), 3) NANBYO
      patients will be regarded as a target for job assistance under the act. In this
      abstract, the author raises the fundamental issues as "Society where NANBYO
      patients can live is equal to that where all people can live", from patient's
      perspective. 

PMID- 24291962
TI  - [Comments on the issue and future strategy of policy toward the rare intractable
      diseases from a standpoint of a neurology specialist].

PMID- 24291963
TI  - [Management of infectious diseases at home care settings].

PMID- 24291964
TI  - [Nutritional management in amyotrophic lateral sclerosis: palliative and end-of
      life care].
AB  - Nutritional intervention in neurological diseases including amyotrophic lateral
      sclerosis (ALS) has drawn attention in recent years. Malnutrition or progressive
      weight loss in the early stage of ALS has been reported as a predictor of poor
      survival prognosis. Percutaneous endoscopic gastrostomy (PEG) is recommended in
      the early stage of ALS to stabilize the body weight and possibly to improve
      patients' quality of life (QOL) or survival prognosis. Clinicians should be
      precisely aware of clinical significance and purposes, and optimal timing of PEG
      in ALS. PEG should be performed in the stages with preserved respiratory function
      (forced vital capacity > 50%, and arterial carbon dioxide pressure < 45 mmHg), to
      avoid early death after PEG and to maintain QOL with nutritional intervention
      through PEG. Although appropriate amount of energy to be administered is yet to
      be established, high calorie diet is expected to be effective for potential
      improvement of survival. PEG is also necessary as a safe administration route of
      opioids for palliative and end-of-life care. 

PMID- 24291965
TI  - [Home care medicine for terminally ill patients].

PMID- 24291966
TI  - [To aim at better home medical care].
AB  - As Japan has been confronting rapid aging of the population, the government is
      promoting home medical care, with reforming medical service policy, offering
      subsidies, and revising payment system of medical service. Hereafter, home
      medical care will play an important role in order to build the integrated
      community care system by cooperating with long-term care services. More
      physicians, not only of specialized clinics, but also of general ones, are
      expected to visit home to provide medical service to their own immobile patients.

PMID- 24291967
TI  - [Clinical factors affecting quality of life and treatment targets in patients
      with myasthenia gravis].
AB  - Presently, myasthenia gravis (MG) is seldom lethal. However, full remission
      without immune treatment is not common, and many patients still find it difficult
      to maintain daily activities. To both determine factors affecting health-related
      quality of life (QOL) and propose an appropriate treatment target for patients
      with MG, we evaluated 640 consecutive patients with MG seen at 11 neurological
      centers. Two-year follow-up data were obtained for 282 patients. Correlations
      between detailed clinical facotrs and the Japanese version of the 15-item MG
      specific QOL scale were analyzed.In the cross-sectional analysis of 640 MG
      patients, multivariate regression revealed that disease severity as evaluated by
      MG Composite (p < 0.0001), but not quantitative MG score, total dose of oral
      prednisolone (p = 0.002), but not current dose, and Cushingoid appearance index
      (p = 0.0004) showed significant negative effects on QOL. Achieving status of
      Minimal Manifestations or better with prednisolone <= 5 mg/day was found to exert
      a major positive impact on QOL in both the cross-sectional and 2-year follow-up
      patient samples and can be recommended as a treatment target.

PMID- 24291968
TI  - [Treatment of pure ocular myasthenia: a proposal from Japan MG registry 2012].
AB  - Autoimmune myasthenia gravis (MG), affecting both ocular and generalized muscles,
      results in various symptoms. Ocular myasthenia (OM) is a form of MG that is
      clinically restricted to extrinsic ocular muscles. Clinical signs of OM can be
      highly variable, ranging from mild unilateral ptosis to complete opthalmoplegia.
      There is no clear evidence supporting corticosteroid use for OM. We studied 123
      patients whose symptoms were limited to ocular muscles with duration of illness
      >= 2 years. We classified them into two groups: 36 patients with ptosis alone
      (the ptosis group) and 87 with diplopia with or without ptosis (the diplopia
      group). Prednisolone (PSL) and immunosuppressants were less frequently used in
      the ptosis group. There were no significant differences in the post-treatment
      condition and quality-of-life (QOL) impairment between the two groups. Forty
      seven (38%) patients who failed to gain minimal manifestation or better status
      with PSL <= 5 mg/day (the unfavorable condition) showed severe QOL impairment.
      Ocular-QMG score was a factor associated with the unfavorable condition. A
      treatment strategy, discriminated by ptosis or diplopia, is necessary to improve
      the ocular symptoms and QOL in OM patients with the unfavorable condition. 

PMID- 24291969
TI  - [Correlation between oral corticosteroid therapy and present disease status in
      myasthenia gravis].
AB  - The aim of this study was to delineate the status of oral corticosteroid therapy
      in myasthenia gravis (MG), and to elucidate the effectiveness of oral
      corticosteroids according to dosing regimen. We evaluated 472 MG patients from 11
      neurological centers in Japan. Disease severity was determined according to MGFA,
      QMG and MG composite. Clinical state following treatment was categorized
      according to MGFA postintervention status. We also completed the Japanese version
      of the 15-item MG-specific QOL scale (MG-QOL15-J). The statistical analysis
      revealed that achievement of minimal manifestation (MM) or better status using
      maximum prednisolone (PSL) dose or reduced PSL dose by 25% or more after adding
      calcineurin inhibitors had significantly positive effects on the present QMG, MG
      composite and MG-QOL15-J. The maximum dose and administration period of PSL did
      not influence present disease severity, but administration period of PSL >=20 mg
      mg/day had negative effects on the present QOL. Achieving a status of MM or
      better by maximum PSL dose or reduced PSL dose combined with other agent may
      improve the present MG status and QOL. 

PMID- 24291970
TI  - [Calcineurin inhibitors and IVIg in the treatment of myasthenia gravis].
AB  - Calcineurin inhibitors (CNIs) and intravenous immunoglobulin (IVIg) are
      immunomodulatory treatments used to treat patients with myasthenia gravis (MG).
      The objective of this study was to describe the clinical features of MG treated
      with CNIs or IVIg. To characterise the clinical features of myasthenic symptoms
      in MG treated with CNIs compared with MG treated without CNIs. Patients with MG
      (676 cases) underwent a multidisciplinary clinical examination (quantitative MG
      score for disease severity (QMG score), MG composite, etc), and we extensively
      reviewed the case histories with current clinical and laboratory evaluations. We
      confirmed CNIs were safe and effective in the treatment of MG in association with
      reduction of corticosteroids. IVIg have efficacy in reducing QMG score in
      patients with moderate to severe MG. 

PMID- 24291971
TI  - [Proposal for rituximab treatment in patients with myasthenia gravis].
AB  - Rituximab (RTX) is a chimeric murine/human monoclonal antibody directed against
      the CD20 surface antigen of B cells. RTX has been for the treatment of non
      Hodikin lymphoma. Recently, RTX was shown to be effective in treating patients
      with myasthenia gravis (MG) who did not show improvement with other
      immunomodulation treatments. However, the evidence of its efficacy is mostly
      limited to a few case series or open-label trials. At the present stage, RTX may
      be permitted to be used in patients who understand the risk of its side effects
      and provide consent for its use in treatment. In future, it will be necessary to
      establish an effective and safe medication protocol of RTX in Japan. 

PMID- 24291972
TI  - [Prognostic factors in Guillain-Barre syndrome].
AB  - The prognosis of Guillain-Barre syndrome (GBS) is not as good as might be
      expected. Among GBS patients, 30% do not respond to intravenous immunoglobulin
      therapy (IVIg) and 10% may worsen after initial treatment (treatment-related
      fluctuation). Recent prospective trials show that 16% of GBS patients are unable
      to walk independently a year after onset of the disease. The prognosis of GBS is
      influenced by clinical, electrophysiological and biological factors, of which the
      clinical factors are most important. The Erasmus GBS Respiratory Insufficiency
      Score (EGRIS) and the modified EGOS (Erasmus GBS Outcome Score) are very useful
      for prediction of mechanical ventilation or aided walking. A small increase in
      serum IgG (delta IgG) two weeks after IVIg treatment is useful as a biological
      prognostic marker that is significantly associated with slow recovery and aided
      walking at 6 months. Use of these factors makes it possible to predict the
      prognosis of GBS patients, and to identify patients with a poor prognosis in the
      early phase of the disease and provide these patients with intensive treatment.
      An accurate prediction of the level of disability is important for improvement of
      the prognosis of GBS. 

PMID- 24291973
TI  - [Fisher syndrome and Bickerstaff brainstem encephalitis].
AB  - Fisher syndrome has been regarded peculiar inflammatory neuropathy with
      ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem
      encephalitis has been considered pure central nervous system disease
      characterized with ophthalmoplegia, ataxia, and consciousness disturbance. Both
      disorder share common features including preceding infection, albumin-cytological
      dissociation, and association with Guillain-Barre syndrome. The discovery of anti
      GQ1b IgG antibodies further supports the view that the two disorder represent a
      single disease spectrum. Currently Bickerstaff brainstem encephalitis can be
      regarded as a variant of Fisher syndrome with central nervous system involvement.

PMID- 24291974
TI  - [A nationwide survey of patients with Bickerstaff brainstem encephalitis:
      diversity of underlying mechanism].
AB  - Bickerstaff brainstem encephalitis (BBE) is characterized by acutely progressive
      bilateral ophthalmoparesis and ataxia with impaired consciousness or pyramidal
      signs, or both; all of which are followed by a monophasic course with good
      recovery. Alike Guillain-Barre syndrome (GBS), BBE is proposed to have an
      autoimmune mechanism triggered by antecedent infection. The nationwide
      epidemiologic survey for BBE, which the author had performed in Japan, suggests
      that BBE consists of typical and atypical cases. Typical BBE has similar
      neurological and serological features to Fisher syndrome and shows good recovery,
      whereas atypical BBE is characterized by delayed recovery, negative anti-GQ1b
      antibodies, and abnormal cerebrospinal fluid and brain MRI findings with other
      possible pathogeneses. 

PMID- 24291976
TI  - [Autoimmune autonomic ganglionopathy and acute autonomic and sensory neuropathy].
AB  - Autonomic neuropathies may occur primarily or secondarily to various underlying
      diseases. Primary autonomic neuropathies are divided into pure autonomic
      neuropathy, autonomic neuropathy with sensory impairment, and autonomic
      neuropathy with sensory and motor impairment based on the concomitance or absence
      of sensory or motor dysfunctions. Autoimmune autonomic ganglionopathy refers to a
      pure autonomic neuropathy, which typically affects both cholinergic and
      adrenergic functions. About a half of the patients with autoimmune autonomic
      ganglionopathy are positive for anti-ganglionic acetylcholine receptor
      antibodies. The mode of progression widely ranges from acute to chronic,
      including that mimicking pure autonomic failure. The number of unmyelinated
      fibers in the sural nerve biopsy specimens tends to decrease with the duration of
      disease become longer. Immunomodulatory treatments are suggested to be effective
      for autoimmune autonomic ganglionopathy. Acute autonomic and sensory neuropathy
      is characterized by autonomic and sensory impairment without motor dysfunction
      that reaches its nadir within a short period of time mimicking the progression of
      Guillain-Barre syndrome. The monophasic clinical course and frequent presence of
      a history of antecedent infections suggests a participation of immune mechanisms.
      The initial symptoms are those related to autonomic disturbance or superficial
      sensory impairment, while deep sensory impairment accompanied by sensory ataxia
      subsequently appears in some patients. Sural nerve biopsy specimens reveal small
      fiber predominant axonal loss, and autopsy cases show neuronal loss in the
      thoracic sympathetic and dorsal root ganglia. Hence, small neurons in the
      autonomic and sensory ganglia may be affected in the initial phase and,
      subsequently, large neurons in the sensory ganglia are damaged in acute autonomic
      and sensory neuropathy. 

PMID- 24291977
TI  - [Overview -- exploring molecular basis of sporadic neurologic disorders].
AB  - During the past three decades, we have witnessed remarkable advances in our
      understanding of the molecular bases of hereditary neurodegenerative diseases,
      which have been accomplished by "positional cloning" strategies. The molecular
      bases of sporadic neurologic disorders, however, largely remain to be elucidated.
      Genome-wide association studies (GWAS) based on the "common disease-common
      variants hypothesis" are currently undertaken to elucidate the disease-relevant
      alleles. Although GWAS have successfully revealed numerous susceptibility genes
      for neurodegenerative diseases, odds ratios associated with risk alleles are
      generally low and account for only a small proportion of estimated heritability.
      In contrast to these observations, involvement of genetic factors with strong
      effect sizes has been suggested even in sporadic neurodegenerative diseases.
      Recent studies have revealed that the effect sizes of the disease-relevant
      alleles that are identified based on comprehensive genome sequencing are
      substantially larger than those identified by GWAS. These findings strongly argue
      for the role of the "common disease-multiple rare variants hypothesis" in
      sporadic neurodegenerative diseases. Given the rapidly improving technologies of
      next generation sequencing (NGS), we expect that NGS will eventually enable us to
      identify all the variants relevant to the molecular bases of neurologic
      disorders. 

PMID- 24291979
TI  - [Toward identification of susceptible genes for sporadic neurodegenerative
      disease].
AB  - Over the past decade, genome-wide association studies (GWASs) using common
      polymorphisms have been conducted to identify genetic risks associated with
      sporadic diseases. Although GWASs have successfully revealed numerous
      susceptibility genes for neurodegenerative diseases, the odds ratios associated
      with these risk alleles are generally low and account for only a small proportion
      of estimated familial clustering. Emerging new technologies for nucleotide
      sequencing such as exome sequencing has provided an exhaustive list of variants,
      which will eventually enable us to explore the role of low-frequency variants of
      large effect sizes in sporadic neurodegenerative diseases. However, it is still a
      statistical challenge to determine which variants are relevant to diseases among
      the numerous candidates, and large sample sizes will be required. Using the clues
      provided by rare familial cases, we have recently identified strong genetic
      factors in Parkinson diseases and in multiple system atrophy based on the
      candidate gene approach. Focusing on the familial aggregation may be an efficient
      approach to identifying risk alleles of large effect sizes in apparently sporadic
      neurodegenerative diseases. 

PMID- 24291978
TI  - [Chromosomal structural variation -- an approach for multiple system atrophy].
AB  - The human genome contains unstable regions that account for 10% of the entire
      genome and are eccentrically located around centromeres and telomeres. They
      consist of several kb or Mb of genome sequence, and present a variety of
      alterations that occur during the replication process, such as repetitions,
      duplications, deletions, and insertions. These structural polymorphisms are
      called copy number variations (CNV). The mutation rate of CNV is 10(2)-10(4)
      times higher than that of single-nucleotide polymorphisms (SNP), and has
      attracted attention as a basis for sporadic disease. The relationship between CNV
      and clinical conditions is complicated. While models based on duplication or
      deletion can be explained as resulting from genetic effect or haploinsufficiency,
      CNV result in a greater range of transcription anomalies, in addition to that of
      a gene coded in the region. Recent studies have revealed the mechanisms of
      transcription and splicing through snRNA and miRNA in the CNV regions. Recently,
      we experienced discordant monozygotic twin (DMZT) cases in which the patients
      developed unilateral multiple system atrophy (MSA). Here, we introduced the
      recent progress regarding CNV and neurodegenerative diseases as it concerns the
      above DMZT cases and other sporadic MSA cases.

PMID- 24291980
TI  - [Epigenome: what we learned from Rett syndrome, a neurological disease caused by
      mutation of a methyl-CpG binding protein].
AB  - Epigenome is defined as DNA and histone modification-dependent gene regulation
      system. Abnormalities in this system are known to cause various neuro
      developmental diseases. We recently reported that neurological symptoms of Rett
      syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding
      protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in
      neuronal cells, and that clinical differences in the identical twins with Rett
      syndrome in the differences in DNA methylation in neuronal genes, but not caused
      by DNA sequence differences. Since central nervus system requires precise gene
      regulation, neurological diseases including Alzheimer and Parkinson diseases may
      be caused by acquired DNA modification (epigenomic) changes that results in
      aberrant gene regulation as well as DNA sequence changes congenitally occurred
      (mutation). 

PMID- 24291981
TI  - [Clinical practice guidelines of the Societas Neurologica Japonica].

PMID- 24291982
TI  - [JSN treatment guideline for Parkinson's disease: its editorial policy and
      problems to be addressed].
AB  - The main part of "JSN Treatment Guideline for Parkinson's Disease 2011" was made
      according to the strict principles of evidence-based medicine(EBM), which was
      described in "Minds: A guidebook for preparation of practice guidelines 2007". In
      brief, the methodology represents determination of recommendations, based on the
      results of the literature searches for evidence for clinical questions by
      systematic methods. This guideline also contains systematic reviews for drug and
      surgical treatments of Parkinson's disease, which is entitled "Effectiveness and
      safety for anti-Parkinsonian drugs and surgical treatments" Handling of treatment
      algorithms, handling of cost-effectiveness analysis of treatments, and
      consideration for the influence of guidelines to the general society are the
      important issues to be addressed in the near future. 

PMID- 24291983
TI  - [Treatment & management guidelines 2011 for Parkinson disease].
AB  - The treatment and management guideline for Parkinson disease (PD) was revised
      based on new findings and published in 2011. The clinical questions and answers
      format was accepted in this new guideline for the convenience of busy clinicians.
      For the early treatment of PD, the agonist first algorhythm was not changed, but
      at the same time, it was emphasized that the under-treatment of motor symptoms
      should be avoided. For the treatment of motor complications, several new drugs
      were added and classified. Recent progresses in the management of non-motor
      symptoms were described in more detail. 

PMID- 24291984
TI  - [Clinical experiences of the Japanese treatment guideline on Parkinson's
      disease].
AB  - The treatment guidelines are prepared for any medical workers to access easily
      when they need to help on a clinical practice. In contrast to the accessibility,
      the guidelines are compiled based on enormous amount of evidences. The current
      version of the Japanese treatment guideline on Parkinson's disease adopted the
      clinical question format and have achieved to supply clear and practical answers
      for users. By clearly providing its treatment alternatives, the guideline allows
      us to strategically identify appropriate treatment measures for individual
      patients in consideration for their QOL as well as ADL. In the meantime, a few
      problems are experienced in the clinical application of the guideline.
      Medications excessively depending on therapeutic recommendations according to the
      guideline policy might result in to be monotonous, as on the previous version of
      the guideline. Simultaneously, there are particular clinical settings in a
      clinical practice for which physicians cannot apply the recommendation by the
      guideline while they recognize the value of the guidelines for the best treatment
      options. Evidence-based therapeutic measures taking into account for patient
      specific problems are important in the treatment of Parkinson's disease. 

PMID- 24291985
TI  - [Practice of the Parkinson's disease in the neurology clinic and the role of
      guideline].

PMID- 24291986
TI  - [Practical guideline of Parkinson's disease in Japan: evaluation and mission of
      future].
AB  - Japanese Society of Neurology (JSN) published Practical guideline for Parkinson's
      Disease (PD) in 2002 and revised version in 2012. This guideline was prepared
      according to the method of evidence-based medicine. We surveyed the daily
      practice of PD to expert neurologists for PD nationwide in Japan. Many
      specialists for PD reported that patients with PD had poor treatment by
      neurologists and neurosurgeons that was out of PD practical guideline. Some
      patients were treated with small dose levodopa despite of Hoehn-Yahr 3 stage.
      Another disabled patients were treated with dopamine agonists alone despite of
      over aged of 80. Many neurologists treated PD patients out of guideline. It is
      important to educate guideline to neurologists and general practioner. 

PMID- 24291987
TI  - [Present status of Japanese neurologists from the questionnaire survey - to
      support women doctor's career advancement].
AB  - Childcare issue and family care issue are critical factors for women doctors to
      make a career as a neurologist in Japan. To know the actual business conditions
      of Japanese neurologists an online questioner survey was conducted. Answers were
      obtained from 737 members of Japanese Society of Neurology and 21 neurological
      medical facilities. Most of the answers were form members at three major
      metropolitan areas such as Tokyo, Osaka and Nagoya. Nobody from some prefectures
      was replied any answer. Almost sixty percent woman doctors had to change their
      working style from full time to part time at their child raising period and had
      difficulty with returning to full time job. Some neurologists have answered they
      used paid vacation to care their families and they felt they could not keep it
      for a longer period. At 70 percent of medical facilities sick child day care
      center were not operated. Opinions form members extremely varied from "In the
      first place woman doctors are unnecessary"to "With the help of the partner I have
      survived my child raising period". 

PMID- 24291988
TI  - [Efforts of gender equality at Kinki University School of Medicine].
AB  - In recent years, medical doctors are in short supply in many university
      hospitals. Retirement of female doctor after delivery is one of the reasons.
      Although they want to return to work after giving birth, they quit unavoidable
      because the working conditions do not match. Then, Kinki university hospital
      established the "provisions for special work arrangements". This work arrangement
      is the wage less, but the working hours is less than the regular. This work
      arrangement increased returner to the university hospital after delivery. 

PMID- 24291989
TI  - [Career support systems for female physicians in Tokyo Women's Medical
      University].
AB  - Tokyo Women's University has career support systems for a female physician. Basic
      career support is provided for a young female physician who has children. Our
      University runs the nursery school which takes care of children in day and night.
      It also helps mothers (female physician) when children are sick. The university
      also provides short time office hours system for doctors who take care of their
      children. Both men and women can take advantage of the system. These systems can
      assist for female physicians to keep their position in hospitals and
      universities. Then, the next step of a career support is a project for higher
      ranking position. Publishing scientific papers and developing good reputation as
      excellent physicians are essential for promotion. How can we support female
      physicians for promotion? Our university establishes a scientific research grant
      and a one-year scholarship for female physicians. We just start the support,
      therefore, we expect out come in future. We have been developing support systems
      for female physicians, however effects have not been sufficient yet. We should
      take more active action to promote female physicians in our society. 

PMID- 24291990
TI  - [Advanced approach for gender-equal career enhancement].

PMID- 24291991
TI  - [Contribution of emergency medicine by neurologists in the western countries:
      residency training is the key].
AB  - Neurologists in the United States actively involve in neurological emergency. Two
      factors have enabled such active contribution: (1) US residency training programs
      in neurology focus on management of neurological emergency as their initial
      training aims. Junior residents receive many lectures in emergent neurology in
      the initial month. (2) The numbers of the faculty members in neurology department
      in the US teaching hospitals are much more than those in Japan, such that each
      faculty member can share the teaching activities. Although the US teaching and
      residency systems in neurological emergency cannot be directly imported to Japan,
      devotion to emergency care in neurological diseases by neurologists should be
      incorporated into management and education in Japan. 

PMID- 24291992
TI  - [Immediate Stroke Life Support: training for neuroresuscitation team in ER].
AB  - Immediate Stroke Life Support (ISLS) is a curriculum for evaluation and
      management of acute stroke syndromes. ISLS was developed by Japan ISLS task force
      consisting of Japanese Association of Acute Medicine (JAAM) and Japanese Congress
      on Neurological Emergencies (JCNE). The course incorporates role play, mannequin
      simulation modalities, and clinical maps. ISLS has undergone a collaborative
      iterative process from Japanese to enable English language / North American
      student participation. ISLS complements the neurological skills and knowledge
      which are essential to cerebral resuscitation. This program will introduce
      teachers to the techniques used in this course, through sequential train-the
      trainer exercises in each of the integrated simulation techniques. 

PMID- 24291993
TI  - [Significant role of neurologists at ER practice].

PMID- 24291994
TI  - [Contribution of neurologists to emergent stroke medicine in Japan].
AB  - Although the demand for emergent stroke management has been increasing, stroke
      specialists are undersupplied in Japan. Neurosurgeons, not neurologists, often
      perform acute stroke care. Since medical management is the mainstream of stroke
      care, neurologists should be fully aware of their role as a commander of the
      stroke care unit. Neurologists have to confront wide-ranging areas of
      neurological diseases including neurological emergency and intractable chronic
      diseases, and such diversity should be respected. Nevertheless, neurological
      departments in the medical schools and hospitals over Japan should constantly
      train a certain number of stroke specialists to meet the demands of patients,
      since stroke is the largest neurological disease in Japan. 

PMID- 24291995
TI  - [What ER physicians expects from neurologist].
AB  - The management of the Department of Emergency (ER) depends on greatly the views
      over the area which a hospital locates, and the organization of each hospital.
      The North American style ER has to treat many patients who show the neurological
      symptoms and neurological diseases. However, neurological examination is the
      special skill of the neurologist, and it takes long time to teach others. In our
      hospital, the neurologist and ER physicians took into consideration cooperatively
      the corresponding method to treat the high frequent neurological symptoms which
      ER physicians were not good at. And this trial was concluded successfully. In
      this paper, we show our trial. 

PMID- 24291996
TI  - [Cardiac reserve in Parkinson's disease and exercise therapy].
AB  - The clinical feature of Parkinson's disease (PD) is not based on the
      identification of the extrapyramidal symptom such as bradykinesia, restinbg
      tremor, rigidity, but also other non-motor symptom (REM sleep disorder, autonomic
      dysfunction, hyposmia etc). According to the cardio-sympathetic dysfunction, it
      is well known abnormal MIBG and orthostatic hypotension finding was seen in early
      disease stage. Furthermore denervation supersensitivity using beta1 stimulant
      correlates the severity of MIBG image, so that this abnormal cardiac function
      induces inadequate cardiac capacity for exercise. Inadequate cardiac capacity
      makes easy fatigability, which correlates the abnormal MIBG image and cardio
      sympathetic damage. So it is difficult to prescribe a specific exercise program
      to meet individual PD patients needs. Music therapy and trunk exercise (for
      example Tai-Chi exercise) are better suited for PD patients. 

PMID- 24291997
TI  - [Impaired exercise-induced blood pressure control in patients with Parkinson's
      disease and related disorders].
AB  - An almost directly proportional increase in blood pressure (BP) and heart rate
      with exercise intensity has been reported in healthy subjects. In contrast,
      patients with multiple system atrophy (MSA) and pure autonomic failure (PAF)
      characterized by autonomic failure exhibit exercise-induced hypotension (EIH),
      prolonged hypotension following the cessation of exercise and exaggerated
      orthostatic hypotension after exercise. EIH, which can be the earliest symptom of
      PAF, provides a clue to the diagnosis of autonomic failure. Exercise-induced
      hypertension, which may be due to adrenergic receptor supersensitivity, may also
      be observed. BP during and after exercise was significantly lower in patients
      with Parkinson's disease (PD) than in healthy subjects. Some PD patients
      exhibited symptoms related to EIH. PD patients who did not achieve 85% of target
      HR with treadmill testing lacked BP elevations during sub-maximal and peak
      exercise. On the other hand, no significant difference was observed in exercise
      induced BP elevations between PD patients with and without cardiac sympathetic
      denervation. Since BP control during exercise in PD was not affected by dosing
      with levodopa, exercise-related BP abnormalities in PD appear to manifest with
      the disease. These findings suggest that PD has impaired exercise-induced BP
      control, but not to the extent of MSA and PAF. 

PMID- 24291998
TI  - [Gastrointestinal dysfunction has important implications for plasma L-dopa
      concentrations in Parkinson's disease].
AB  - Gastrointestinal motility dysfunctions including anorexia, nausea, heartburn,
      bloating, etc. are common and frequent complication of Parkinson's disease (PD).
      Degeneration of enteric nerves system is supposed to be a pathogenesis of these
      symptoms. Impairment of gastric emptying (GE) leads to retardation of the drug
      delivery from stomach to jejunum, so that PD patients with GE impairment show the
      delayed elevation of plasma L-dopa concentration. Disturbance of L-dopa
      absorption will result in wearing-off and delayed-on, and these are called motor
      fluctuation. In our investigation, 69% of PD patients who exhibited delayed
      elevation of plasma L-dopa concentration complicated GE impairment, whereas only
      22% of patients with normal L-dopa level showed GE retardation (p = 0.0044,
      chi(2)-test). Serotonin 5-HT4 agonist and dopamine D2 antagonist are useful to
      improve GE impairment in PD. These drugs stimulate the postganglionic cholinergic
      fiber to release acetylcholine amongst the enteric nerves system and facilitate
      the gastrointestinal tract. Rikkunshi-to, dietary herbal medicine, is also
      administered to ameliorate gastrointestinal symptoms in PD. Rikkunshi-to is
      reported to improve erratic GE and reduce the variation of plasma L-dopa level.
      Recently, intestinal continuous L-dopa administration is expected as the
      potential solution for L-dopa induced motor fluctuation in advanced PD. 

PMID- 24291999
TI  - [Cognitive function and blood pressure regulation in Lewy body diseases].
AB  - It is well known that autonomic failure is severer in patients with dementia with
      Lewy bodies (DLB) compared with patients with Parkinson's disease (PD). According
      to the Braak's hypothesis, Lewy bodies first appear in the olfactory bulb or
      peripheral autonomic nervous system. Lewy bodies in the peripheral autonomic
      nervous system ascend to dorsal motor nuclei of vagus nerve, while those in the
      olfactory bulb expand to the limbic system. Lewy bodies later attain the
      substantia nigra. However, it seems that Braak staging can not explain difference
      in severity of autonomic failure between DLB and PD. As a possibility, in DLB
      patients with significant autonomic failure, Lewy bodies may have been localized
      to the peripheral autonomic nervous system in a long time before onset of
      dementia or parkinsonism, and propagation of Lewy bodies into the central nervous
      system may be initiated by apparition of certain promotion factor, such as ageing
      and amyloid-beta. 

PMID- 24292000
TI  - [Cognitive adverse effects of anticholinergic medication for overactive bladder
      in PD/DLB].
AB  - Overactive bladder (OAB) is a common autonomic disorder due mostly to lesions in
      the micturition-inhibiting area (D1 dopaminergic pathway in the basal ganglia) in
      Parkinson's disease (PD) and dementia with Lewy bodies (DLB). anticholinergic
      drugs are the mainstay in the treatment of OAB. However, since 1997,
      anticholinergic adverse events on the cognitive function have been recognized.
      Drugs with less lipophilic, less permeable through the blood-brain barrier are
      the choice in the treatment of OAB in elderly neurologic patients. 

PMID- 24292001
TI  - [Clinical feature of ALS with communication disturbance; the possibility to
      communicate in TLS].
AB  - In the subsets of amyotrohic lateral sclerosis (ALS), totally-locked in state
      (TLS) is shown as the result of marked progression of motor neuron degeneration.
      In TLS, patients are impossible to move any voluntary muscles. As the result,
      patients with TLS cannot communicate with any augmentative and alternative
      communication devices(AACD) at present. To find the AACD that enables for TLS to
      communicate, we examined the clinical character, brain MRI, SPECT and evoked
      potentials in TLS. Brain MRI showed marked brain atrophy including the brainstem,
      but the occipital lobe was spared. SPECT and visual evoked potentials (VEP)
      showed preserved physiological function of the occipital lobe in TLS. The results
      suggest that neuronal degeneration in TLS is not restricted to motor system, but
      that the visual pathways are spared. Patients with TLS may be possible to use
      AACD that utilize the visual pathway.

PMID- 24292002
TI  - [Predictors the progression of communication impairment in ALS tracheostomy
      ventilator users].
AB  - We investigated predictive factors associatied with progression of communication
      impairment in 76 patients with amyotrophic lateral sclerosis (ALS) using
      tracheostomy ventilation. We classified the patients into the following three
      groups: patients capable of communication (stage I), patients with difficulties
      in communication (stage II to IV), and patients incapable of communication (stage
      V: so-called totally locked-in state) (Hayashi, et al. Clin Neurol 2013). There
      were no significant difference of disease duration across stages. Statistically
      significant differences were noted in the time of ventilator use, the time of
      tube feeding, and the time of complete quadriplegia among the 3 groups (Kruskal
      Wallis). Multivariate analyses showed that the durations from onset to the time
      of ventilator use and complete quadriplegia had significant effecte on the
      progression from stage I to II, and that the duration from onset to the
      development of overt oculomotor limitation had signicant effect on the
      progression from stage IV to V. Faster progression may predict the extent of
      communication impairment after ventilator use.Accurate prediction of
      communication impairment after ventilator use may promote medical and social
      preparation including early application of the brain-machine interface for future
      communication problems in ALS patients.

PMID- 24292003
TI  - [Amyotrophic lateral sclerosis in totally locked-in state].
AB  - Seven autopsy patients with amyotrophic lateral sclerosis (ALS) in totally locked
      in state (TLS) were examined neuropathologically. The patients were composed of 4
      males and 3 females, and 3 with familial, 1 sporadic but with mutation in SOD1
      gene, and 3 sporadic patients with unremarkable gene mutation. The brains weighed
      715, 783, 1,019, 1,050, 1,170, 1,190 or 1,233 g. The tegmentum of the brain stem
      was markedly degenerated in every patient, and the tracts relating to the somatic
      sensory and auditory were involved in the lesions. 

PMID- 24292004
TI  - [Development of a cognitive BMI "neurocommunicator" as a communication aid of
      patients with severe motor deficits].
AB  - A cognitive brain-machine interface (BMI), "neurocommunicator" has been developed
      by the author's research group in AIST in order to support communication of
      patients with severer motor deficits. The system can identify candidate messages
      (pictograms) in real time from electroencephalography (EEG) data, combining three
      core technologies; 1) a portable/wireless EEG recorder; 2) a high-speed and high
      accuracy decoding algorithm; and 3) a hierarchical message generation system. The
      accuracy of the model at single predictions of the target was generally over 95%,
      corresponding to about 32 bits per minute for normal subjects. Monitor
      experiments have been also started for patients at their home, in which further
      technical improvements are required. 

PMID- 24292005
TI  - [Communication with ALS patients: neurosurgical approach].
AB  - By progression of the disease, motor neurons degenerate in patients with
      amyotrophic lateral sclerosis (ALS) eventually lose nearly all voluntary muscles
      in the body. They are awake and aware but cannot move or communicate (locked-in
      state). Since the function of the brain is preserved, one possible measure to
      support their communication is to interpret their motor intention by decoding
      (deciphering) brain signals and present it with external devices. This technology
      called "brain-machine interface (BMI)" is now close to clinical use in Japan and
      USA.In our system, we record electrocorticogram (ECoG) obtained with subudural
      electrodes during their motor imagery, decode it and determine the movement they
      intended. So far, one patient of ALS with severe paralysis, implanted with this
      electrodes, successfully operated the PC communication tool only by thinking. 

PMID- 24292006
TI  - Separation of no-carrier-added rhenium from bulk tantalum by the sodium malonate
      PEG aqueous biphasic system.
AB  - The aqueous biphasic system (ABS) involving sodium malonate-polyethylene glycol
      (PEG) phases has been applied for the first time for separation of no-carrier
      added (183)Re (T1/2=70 d) from alpha-particle irradiated bulk tantalum target.
      The various ABS conditions were applied for investigating the separation by
      varying pH, temperature, PEG-molecular weight, concentration of salt. The
      extraction pattern was hardly affected by change in pH and the molecular weight
      of PEG. One step separation of nca (183)Re from Ta was achieved at the optimal
      conditions of (i) 50% (w/w) PEG-4000-2 M sodium malonate, 40  degrees C and (ii)
      50% (w/w) PEG-4000-3 M sodium malonate, room temperature (27  degrees C).

PMID- 24292007
TI  - Estimation of background spectrum in a shielded HPGe detector using Monte Carlo
      simulations.
AB  - Monte Carlo simulations are powerful tools used to estimate the background gamma
      radiation detected by high-resolution gamma-ray spectrometry systems with a HPGe
      (high purity germanium) detector contained inside a lead shield. The purpose of
      this work was to examine the applicability of Monte Carlo simulations to predict
      the optimal lead thickness necessary to reduce the background effect in
      spectrometer measurements. GEANT4 code was applied to simulate the background
      radiation spectrum at different thicknesses of lead. The simulated results were
      compared with experimental measurements of background radiation taken at the same
      shielding thickness. The results show that the background radiation detected
      depends on the thickness, size and lining of the shield. Simulation showed that
      12 cm lead thick is the optimal shielding thickness.

PMID- 24292008
TI  - The novel MAPT mutation K298E: mechanisms of mutant tau toxicity, brain pathology
      and tau expression in induced fibroblast-derived neurons.
AB  - Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative
      diseases characterized by behavioural and executive impairment, language
      disorders and motor dysfunction. About 20-30% of cases are inherited in a
      dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT)
      cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP
      17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with
      FTDP-17T. Neuropathological studies of post-mortem brain showed widespread
      neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in
      neurons and glia. Molecular studies demonstrated that the K298E mutation affects
      both protein function and alternative mRNA splicing. Fibroblasts from a skin
      biopsy of the proband taken at post-mortem were directly induced into neurons
      (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as
      contributing new knowledge on MAPT mutations in FTDP-17T, this is the first
      example of the successful generation of iNs from skin cells retrieved post
      mortem.

PMID- 24292010
TI  - A parametric finite element analysis of the compacted bone-cement interface
      following balloon kyphoplasty.
AB  - Treating fractures of the spine is a major challenge for the medical community
      with an estimated 1.4 million fractures per annum worldwide. While a considerable
      volume of study exists on the biomechanical implications of balloon kyphoplasty,
      which is used to treat these fractures, the influence of the compacted bone
      cement region properties on stress distribution within the vertebral body remains
      unknown. The following article describes a novel method for modelling this
      compacted bone-cement region using a geometry-based approach in conjunction with
      the knowledge of the bone volume fractions for the native and compacted bone
      regions. Three variables for the compacted region were examined, as follows: (1)
      compacted thickness, (2) compacted region Young's modulus and (3) friction
      coefficient. Results from the model indicate that the properties of the compacted
      bone-cement region can affect stresses in the cortical bone and cement by up to
      +28% and -40%, respectively. These findings demonstrate the need for further
      investigation into the effects of the compacted bone-cement interface using
      computational and experimental methods on multi-segment models. 

PMID- 24292009
TI  - Early loss of oligodendrocytes in human and experimental neuromyelitis optica
      lesions.
AB  - Neuromyelitis optica (NMO) is a chronic, mostly relapsing inflammatory
      demyelinating disease of the CNS characterized by serum anti-aquaporin 4 (AQP4)
      antibodies in the majority of patients. Anti-AQP4 antibodies derived from NMO
      patients target and deplete astrocytes in experimental models when co-injected
      with complement. However, the time course and mechanisms of oligodendrocyte loss
      and demyelination and the fate of oligodendrocyte precursor cells (OPC) have not
      been examined in detail. Also, no studies regarding astrocyte repopulation of
      experimental NMO lesions have been reported. We utilized two rat models using
      either systemic transfer or focal intracerebral injection of recombinant human
      anti-AQP4 antibodies to generate NMO-like lesions. Time-course experiments were
      performed to examine oligodendroglial and astroglial damage and repair. In
      addition, oligodendrocyte pathology was studied in early human NMO lesions. Apart
      from early complement-mediated astrocyte destruction, we observed a prominent,
      very early loss of oligodendrocytes and oligodendrocyte precursor cells (OPCs) as
      well as a delayed loss of myelin. Astrocyte repopulation of focal NMO lesions was
      already substantial after 1 week. Olig2-positive OPCs reappeared before NogoA
      positive, mature oligodendrocytes. Thus, using two experimental models that
      closely mimic the human disease, our study demonstrates that oligodendrocyte and
      OPC loss is an extremely early feature in the formation of human and experimental
      NMO lesions and leads to subsequent, delayed demyelination, highlighting an
      important difference in the pathogenesis of MS and NMO.

PMID- 24292011
TI  - Mathematical modelling of peristaltic propulsion of viscoplastic bio-fluids.
AB  - This article studies theoretically the transportation of rheological viscoplastic
      fluids through physiological vessels by continuous muscle contraction and
      relaxation, that is, peristalsis. Both cases of planar and cylindrical
      physiological vessels are considered. A mathematical model is developed under
      long wavelength and low Reynolds number approximations. Expressions for axial
      velocity in core region, axial velocity in plug flow region, volume flow rate and
      pressure gradient in non-dimensional form are obtained. A comparative study of
      velocity profiles, pressure distribution, friction force and mechanical
      efficiency for different viscoplastic liquids is conducted. The influence of
      width of plug flow region, shear rate strain index and yield stress index on the
      pressure distribution, friction force and mechanical efficiency is elaborated.
      The study is relevant to gastric fluid mechanics and also non-Newtonian
      biomimetic pump hazardous waste systems exploiting peristaltic mechanisms. 

PMID- 24292012
TI  - Biocatalytic analysis of biomarkers for forensic identification of gender.
AB  - A new biocatalytic assay analyzing the simultaneous presence of creatine kinase
      (CK) and alanine transaminase (ALT) was developed aiming at the recognition of
      biofluids of different gender for forensic applications. Knowing the difference
      in the concentrations of CK and ALT enzymes in the blood of healthy adults of
      male and female groups we mimicked the samples of different gender with various
      CK-ALT concentrations. The analysis was performed using a multi-enzyme/multi-step
      biocatalytic cascade where the differences in both included enzymes resulted in
      an amplified difference in the final analytical response. The analysis performed
      in human serum solutions allowed discrimination of samples corresponding to
      male/female groups. The robustness of the developed analysis allowed
      determination of the gender for serum solutions after their drying and ageing at
      least for 1 hour. Importantly for forensic applications, reaction with a
      chromogenic reactant nitroblue tetrazolium allowed qualitative discrimination of
      the "male" and "female" samples by the naked eye. 

PMID- 24292013
TI  - Cell-to-cell expression variability followed by signal reinforcement
      progressively segregates early mouse lineages.
AB  - It is now recognized that extensive expression heterogeneities among cells
      precede the emergence of lineages in the early mammalian embryo. To establish a
      map of pluripotent epiblast (EPI) versus primitive endoderm (PrE) lineage
      segregation within the inner cell mass (ICM) of the mouse blastocyst, we
      characterized the gene expression profiles of individual ICM cells. Clustering
      analysis of the transcriptomes of 66 cells demonstrated that initially they are
      non-distinguishable. Early in the segregation, lineage-specific marker expression
      exhibited no apparent correlation, and a hierarchical relationship was
      established only in the late blastocyst. Fgf4 exhibited a bimodal expression at
      the earliest stage analysed, and in its absence, the differentiation of PrE and
      EPI was halted, indicating that Fgf4 drives, and is required for, ICM lineage
      segregation. These data lead us to propose a model where stochastic cell-to-cell
      expression heterogeneity followed by signal reinforcement underlies ICM lineage
      segregation by antagonistically separating equivalent cells. 

PMID- 24292015
TI  - Assessment of a brain-tumour-specific Patient Concerns Inventory in the neuro
      oncology clinic.
AB  - PURPOSE: Brain tumour patients may struggle to express their concerns in the
      outpatient clinic, creating a physician-focused rather than a shared agenda. We
      created a simple, practical brain-tumour-specific holistic needs assessment (HNA)
      tool for use in the neuro-oncology outpatient clinic. METHODS: We posted the
      brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult
      brain tumour attendees to a neuro-oncology outpatient clinic. Participants
      brought the completed PCI to their clinic consultation. Patients and staff
      provided feedback. RESULTS: Seventy seven patients were eligible and 53
      participated (response rate = 68%). The PCI captured many problems absent from
      general cancer checklists. The five most frequent concerns were fatigue, fear of
      tumour coming back, memory, concentration, and low mood. Respondents used the PCI
      to formulate 105 specific questions, usually about the meaning of physical or
      psychological symptoms. Patients and staff found the PCI to be useful, and
      satisfaction with the instrument was high. CONCLUSIONS: This study demonstrates
      the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The
      combination of a brain-tumour-specific concerns checklist and an intervention to
      focus patient agenda creates a simple and efficient HNA tool.

PMID- 24292014
TI  - Der1 promotes movement of misfolded proteins through the endoplasmic reticulum
      membrane.
AB  - Misfolded proteins of the secretory pathway are extracted from the endoplasmic
      reticulum (ER), polyubiquitylated by a protein complex termed the Hmg-CoA
      reductase degradation ligase (HRD ligase) and degraded by cytosolic 26S
      proteasomes. The movement of these proteins through the lipid bilayer is assumed
      to occur via a protein-conducting channel of unknown nature. We show that the
      integral membrane protein Der1 oligomerizes, which relies on its interaction with
      the scaffolding protein Usa1. Mutations in the transmembrane domains of Der1
      block the passage of soluble proteins across the ER membrane. As determined by
      site-specific photocrosslinking, the ER-luminal exposed parts of Der1 are in
      spatial proximity to the substrate receptor Hrd3, whereas the membrane-embedded
      domains reside adjacent to the ubiquitin ligase Hrd1. Intriguingly, both regions
      also form crosslinks to client proteins. Our data imply that Der1 initiates the
      export of aberrant polypeptides from the ER lumen by threading such molecules
      into the ER membrane and routing them to Hrd1 for ubiquitylation. 

PMID- 24292016
TI  - Development and validation of the Short-Form Survivor Unmet Needs Survey (SF
      SUNS).
AB  - PURPOSE: The Survivor Unmet Needs Survey (SUNS) is one of the only unmet needs
      measures that was developed and evaluated utilising a population-based sample of
      cancer survivors. At 89 items, the current scale is quite burdensome. The current
      study aimed to develop a valid and reliable short version of this survey.
      METHODS: A heterogeneous sample of 1,589 cancer survivors, aged 19 years or over
      at diagnosis, diagnosed with a histologically confirmed cancer in the previous 12
      to 60 months, completed the SUNS. Using these data, we employed a combined
      theoretical and statistical method of reducing the number of items in the SUNS.
      The shortened survey was examined for construct validity, internal consistency,
      discriminant validity and floor and ceiling effects. RESULTS: Fifty-nine items
      were removed. Construct validity closely reflected the original structure of the
      SUNS. However, all items from the Emotional health and Relationships domains
      loaded onto one factor. Cronbach's alpha for the final four domains were 0.85 or
      above, demonstrating strong internal consistency. Intra-class correlations of the
      three domains from the original survey (Financial concerns, Information and
      Access and continuity of care) and shortened survey were high (>0.9).
      Discriminant validity illustrated the short-form SUNS' ability to discriminate
      between those who had recently received treatment and those who had not.
      CONCLUSIONS: This study describes the development and psychometric evaluation of
      the short-form SUNS (SF-SUNS). Future studies should confirm the test-retest
      reliability and predictive validity of the SF-SUNS utilising large, independent,
      population-based samples of cancer survivors.

PMID- 24292017
TI  - Association between race and physical functioning limitations among breast cancer
      survivors.
AB  - PURPOSE: The goal of this study was to examine differences in physical
      functioning limitations among African-American and white breast cancer survivors.
      METHODS: Data were analyzed from 115 African-American and 712 white breast cancer
      survivors who responded to a hospital registry-based survey. Physical functioning
      limitations were assessed using a series of eight questions in which individuals
      were asked about their ability to perform a physical task such as walking a
      quarter of a mile. A four-category summary score, representing overall severity
      of limitation, was created using participant responses to the eight questions.
      Ordinal logistic regression was used to estimate the odds ratio (OR) and 95%
      confidence interval (CI) for the association between race and physical
      functioning limitation adjusted for potential confounders. RESULTS: In the
      unadjusted model, the African-American breast cancer survivors were more than
      twice as likely to have a greater degree of physical functioning limitation
      compared to their white counterparts (OR 2.31; 95% CI 1.59, 3.38). After
      adjustment for covariates, including body mass index (BMI), the race OR was
      attenuated and no longer statistically significant (OR 1.44; 95% CI 0.92, 2.27).
      CONCLUSIONS: Findings from this study showed that African-American breast cancer
      survivors were more likely to have worse physical functioning limitations than
      their white counterparts; however, much of this disparity was due to racial
      differences in other variables such as BMI. Future research should focus on
      effective interventions targeting modifiable risk factors of physical functioning
      limitations among breast cancer survivors with the goal of improving quality of
      life.

PMID- 24292018
TI  - The effect of age on post-activation depression of the upper limb H-reflex.
AB  - PURPOSE: Post-activation depression (PaD) refers to the inhibition of the H
      reflex induced by a preceding conditioning stimulus able to activate the
      afferents mediating the H-reflex itself. PaD can be investigated assessing the
      frequency-related depression of the H-reflex. This parameter, which is highly
      correlated to the severity of spasticity, has been used in the longitudinal
      assessment of spastic patients, in particular to assess the effect of drugs and
      rehabilitation over the years. However, in such longitudinal assessment, changes
      observed might be age related and not only disease related. The aim of this study
      was to investigate the possible age effects on PaD. METHODS: The frequency
      related depression of the flexor carpi radialis (FCR) H-reflex was examined in
      two groups of young (20 subjects; 28 +/- 3 years) and aged (18 subjects; 69 +/- 6
      years) healthy subjects. PaD was evaluated by comparing the H-reflex amplitudes
      obtained with a stimulation frequency of 0.1 Hz with those obtained using higher
      frequencies (0.33-0.5-1-2 Hz). RESULTS: The results showed that frequency-related
      depression of the FCR H-reflex is similar in young and elderly subjects at all
      frequencies, with the exception of 2 Hz. CONCLUSION: Our study shows that ageing
      does not affect the frequency-related depression of the FCR H-reflex at the
      frequencies of 1 Hz or lower, supporting the reliability of this method to assess
      PaD in the clinical practice, particularly for the longitudinal assessment of
      spasticity. A decrease of GABA-ergic presynaptic inhibition seems to be the more
      likely explanation for the age-related changes that we observed at the frequency
      of 2 Hz.

PMID- 24292019
TI  - Maximal and explosive strength training elicit distinct neuromuscular
      adaptations, specific to the training stimulus.
AB  - PURPOSE: To compare the effects of short-term maximal (MST) vs. explosive (EST)
      strength training on maximal and explosive force production, and assess the
      neural adaptations underpinning any training-specific functional changes.
      METHODS: Male participants completed either MST (n = 9) or EST (n = 10) for 4
      weeks. In training participants were instructed to: contract as fast and hard as
      possible for ~1 s (EST); or contract progressively up to 75% maximal voluntary
      force (MVF) and hold for 3 s (MST). Pre- and post-training measurements included
      recording MVF during maximal voluntary contractions and explosive force at 50-ms
      intervals from force onset during explosive contractions. Neuromuscular
      activation was assessed by recording EMG RMS amplitude, normalised to a maximal M
      wave and averaged across the three superficial heads of the quadriceps, at MVF
      and between 0-50, 0-100 and 0-150 ms during the explosive contractions. RESULTS:
      Improvements in MVF were significantly greater (P < 0.001) following MST (+21 +/-
      12%) than EST (+11 +/- 7%), which appeared due to a twofold greater increase in
      EMG at MVF following MST. In contrast, early phase explosive force (at 100 ms)
      increased following EST (+16 +/- 14%), but not MST, resulting in a time * group
      interaction effect (P = 0.03), which appeared due to a greater increase in EMG
      during the early phase (first 50 ms) of explosive contractions following EST (P =
      0.052). CONCLUSIONS: These results provide evidence for distinct neuromuscular
      adaptations after MST vs. EST that are specific to the training stimulus, and
      demonstrate the independent adaptability of maximal and explosive strength.

PMID- 24292021
TI  - Electrochemical engineering of hollow nanoarchitectures: pulse/step anodization
      (Si, Al, Ti) and their applications.
AB  - Hollow nanoarchitectured materials with straight channels play a crucial role in
      the fields of renewable energy, environment and biotechnology due to their one
      dimensional morphology and extraordinary properties. The current challenge is the
      difficulty on tailoring hollow nanoarchitectures with well-controlled morphology
      at a relatively low cost. As a conventional technique, electrochemistry exhibits
      its unique advantage on machining nanostructures. In this review, we present the
      progress of electrochemistry as a valuable tool in construction of novel hollow
      nanoarchitectures through pulse/step anodization, such as surface pre-texturing,
      modulated, branched and multilayered pore architectures, and free-standing
      membranes. Basic principles for electrochemical engineering of mono- or multi
      ordered nanostructures as well as free-standing membranes are extracted from
      specific examples (i.e. porous silicon, aluminum and titanium oxide). The
      potential of such nanoarchitectures are further demonstrated for the applications
      of photovoltaics, water splitting, organic degradation, nanostructure templates,
      biosensors and drug release. The electrochemical techniques provide a powerful
      approach to produce nanostructures with morphological complexity, which could
      have far-reaching implications in the design of future nanoscale systems. 

PMID- 24292020
TI  - A recombinant influenza virus vaccine expressing the F protein of respiratory
      syncytial virus.
AB  - Infections with influenza and respiratory syncytial virus (RSV) rank high among
      the most common human respiratory diseases worldwide. Previously, we developed a
      replication-incompetent influenza virus by replacing the coding sequence of the
      PB2 gene, which encodes one of the viral RNA polymerase subunits, with that of a
      reporter gene. Here, we generated a PB2-knockout recombinant influenza virus
      expressing the F protein of RSV (PB2-RSVF virus) and tested its potential as a
      bivalent vaccine. In mice intranasally immunized with the PB2-RSVF virus, we
      detected high levels of antibodies against influenza virus, but not RSV. PB2-RSVF
      virus-immunized mice were protected from a lethal challenge with influenza virus
      but experienced severe body weight loss when challenged with RSV, indicating that
      PB2-RSVF vaccination enhanced RSV-associated disease. These results highlight one
      of the difficulties of developing an effective bivalent vaccine against influenza
      virus and RSV infections. 

PMID- 24292023
TI  - Fecal metabonomic study of a polysaccharide, MDG-1 from Ophiopogon japonicus on
      diabetic mice based on gas chromatography/time-of-flight mass spectrometry (GC
      TOF/MS).
AB  - Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with systemic
      complications and has been a worldwide epidemic. Ophiopogon japonicus is a
      traditional Chinese medicine used to treat diabetes for thousands of years. From
      our previous work, we know that MDG-1, a water-soluble beta-D-fructan
      polysaccharide from O. japonicas could treat T2DM experimentally. However, MDG-1
      is poorly absorbed and its mechanism of action is still unknown. Therefore, a GC
      TOF/MS-based metabonomic approach in combination with multivariate statistical
      analysis was performed to investigate the mechanism of MDG-1 in a spontaneous
      diabetic model. Female diabetic KKay mice (21 weeks old) were randomly divided
      into a diabetic group (n = 6, gavaged with distilled water) and a MDG-1-Diabetic
      group (n = 7, gavaged with MDG-1, 300 mg kg(-1)) and female C57BL/6 mice (21
      weeks old) were set as controls (n = 6, gavaged with distilled water). After 8
      weeks of treatment, feces samples were collected for GC-TOF/MS analysis.
      Consequently, 12 potential biomarkers were identified, including monosugars (D
      tagatose, D-lyxose, D-erythrose, xylo-hexos-5-ulose, 2-deoxy-galactose),
      butanedioic acid, amino acids (phenylalanine, L-lysine, L-methionine, L-aspartic
      acid) and purine derivatives (7H-purine, 2'-deoxyinosine). We assume the
      monosugars and butanedioic acid were the fermentation products of MDG-1 by
      intestinal microbes and MDG-1 actions against diabetes might be accomplished
      through the absorbable monosugars and butanedioic acid via suppressing intestinal
      glucose absorption, enhancing liver glycogenesis, inhibiting glycogenolysis and
      promoting GLP-1 secretion. Besides, MDG-1 might alleviate diabetes and diabetic
      nephropathy by reducing 7H-purine and 2'-deoxyinosine. Further omics-driven
      studies including genomics, proteomics and metabonomics were considered to be
      carried out to provide direct evidence of gut microbiome contribution to MDG-1
      actions.

PMID- 24292024
TI  - A one-layer recurrent neural network for constrained nonsmooth invex
      optimization.
AB  - Invexity is an important notion in nonconvex optimization. In this paper, a one
      layer recurrent neural network is proposed for solving constrained nonsmooth
      invex optimization problems, designed based on an exact penalty function method.
      It is proved herein that any state of the proposed neural network is globally
      convergent to the optimal solution set of constrained invex optimization
      problems, with a sufficiently large penalty parameter. In addition, any neural
      state is globally convergent to the unique optimal solution, provided that the
      objective function and constraint functions are pseudoconvex. Moreover, any
      neural state is globally convergent to the feasible region in finite time and
      stays there thereafter. The lower bounds of the penalty parameter and convergence
      time are also estimated. Two numerical examples are provided to illustrate the
      performances of the proposed neural network. 

PMID- 24292025
TI  - Exposure to DEHP and MEHP from hatching to adulthood causes reproductive
      dysfunction and endocrine disruption in marine medaka (Oryzias melastigma).
AB  - Concern has increased regarding the adverse effects of di-(2-ethylhexyl)
      phthalate (DEHP) on reproduction. However, limited information is available on
      the effects of DEHP in marine organisms. The aim of the present study was to
      examine whether long-term exposure to DEHP and its active metabolite mono-(2
      ethylhexyl)-phthalate (MEHP) disrupts endocrine function in marine medaka
      (Oryzias melastigma). Marine medaka larvae were exposed to either DEHP (0.1 and
      0.5mg/L) or MEHP (0.1 and 0.5mg/L) for 6 months, and the effects on reproduction,
      sex steroid hormones, liver vitellogenin (VTG), gonad histology and the
      expression of genes involved in the hypothalamic-pituitary-gonad (HPG) axis were
      investigated. Exposure to DEHP, but not MEHP, from hatching to adulthood
      accelerated the start of spawning and decreased the egg production of exposed
      females. Moreover, exposure to both DEHP and MEHP resulted in a reduction in the
      fertilization rate of oocytes spawned by untreated females paired with treated
      males. A significant increase in plasma 17beta-estradiol (E2) along with a
      significant decrease in testosterone (T)/E2 ratios was observed in males, which
      was accompanied by the upregulation of ldlr, star, cyp17a1, 17betahsd, and cyp19a
      transcription in the testis. Increased concentrations of T and E2 were observed
      in females, which was consistent with the upregulation of ldlr. The expression of
      brain gnrhr2, fshbeta, cyp19b and steroid hormone receptor genes also
      corresponded well with hormonal and reproductive changes. The liver VTG level was
      significantly increased after DEHP and MEHP exposure in males. DEHP induced
      histological changes in the testes and ovaries: the testes displayed a reduced
      number of spermatozoa, and the ovaries displayed an increased number of atretic
      follicles. In addition, the tissue concentrations of MEHP, MEHHP and MEOHP in
      DEHP-exposed groups were much higher than those in MEHP-exposed groups, and there
      were no dose- or sex-specific effects. Thus, DEHP exerts more obvious toxic
      effects compared with MEHP. There were some commonalities in the toxic effects
      and molecular mechanisms of DEHP and MEHP, suggesting that some of the toxic
      effects of DEHP may be induced by both DEHP itself and DEHP metabolites
      (including MEHP). Taken together, these results indicate that exposure to DEHP
      and MEHP from hatching to adulthood causes endocrine disruption with sex-specific
      effects in marine medaka, with males being more sensitive than females. 

PMID- 24292026
TI  - Pathology working group review of histopathologic specimens from three laboratory
      studies of diclofenac in trout.
AB  - While the pathology peer review/pathology working group (PWG) model has long been
      used in mammalian toxicologic pathology to ensure the accuracy, consistency, and
      objectivity of histopathology data, application of this paradigm to
      ecotoxicological studies has thus far been limited. In the current project, the
      PWG approach was used to evaluate histopathologic sections of gills, liver,
      kidney, and/or intestines from three previously published studies of diclofenac
      in trout, among which there was substantial variation in the reported
      histopathologic findings. The main objectives of this review process were to
      investigate and potentially reconcile these interstudy differences, and based on
      the results, to establish an appropriate no observed effect concentration (NOEC).
      Following a complete examination of all histologic sections and original
      diagnoses by a single experienced fish pathologist (pathology peer review), a two
      day PWG session was conducted to allow members of a four-person expert panel to
      determine the extent of treatment-related findings in each of the three trout
      studies. The PWG was performed according to the United States Environmental
      Protection Agency (US EPA) Pesticide Regulation (PR) 94-5 (EPA Pesticide
      Regulation, 1994). In accordance with standard procedures, the PWG review was
      conducted by the non-voting chairperson in a manner intended to minimize bias,
      and thus during the evaluation, the four voting panelists were unaware of the
      treatment group status of individual fish and the original diagnoses associated
      with the histologic sections. Based on the results of this review, findings
      related to diclofenac exposure included minimal to slightly increased thickening
      of the gill filament tips in fish exposed to the highest concentration tested
      (1,000 MUg/L), plus a previously undiagnosed finding, decreased hepatic glycogen,
      which also occurred at the 1,000 MUg/L dose level. The panel found little
      evidence to support other reported effects of diclofenac in trout, and thus the
      overall NOEC was determined to be >320 MUg/L. By consensus, the PWG panel was
      able to identify diagnostic inconsistencies among and within the three prior
      studies; therefore this exercise demonstrated the value of the pathology peer
      review/PWG approach for assessing the reliability of histopathology results that
      may be used by regulatory agencies for risk assessment.

PMID- 24292027
TI  - Experience of a tertiary care center on 100 newborns with neural tube defects.
AB  - The aim of this study was to analyze the sociodemographic features, postoperative
      complications, long-term problems, and cost of care of patients followed in the
      neonatal intensive care unit (NICU) with a diagnosis of neural tube defects
      (NTDs). Babies with NTD followed in the Neonatology Unit of Ondokuz Mayis
      University Faculty of Medicine between January 2003 and December 2011 were
      analyzed retrospectively. One hundred (1.2%) of 8408 babies admitted to the NICU
      were diagnosed as NTD during the study period. Of the cases with NTD, 74% of
      mothers were graduates of primary school/illiterate, and none had used folic acid
      (FA) preconceptionally. Prenatal diagnosis was made in 72%, but parents had
      chosen not to terminate the pregnancy. The most frequent type and site of NTD was
      meningomyelocele (82%) of the lumbosacral region (36%). In 80% of the babies, the
      NTD sac was closed with in the first 72 hours of life. The most frequently
      observed postoperative complications were wound infection and septicemia. The
      mortality rate of babies with NTD during the follow-up period was 7%, and all
      deaths occurred in the first year of life. Sixty-two percent of the patients had
      neurologic deficits on follow-up. Patients were rehospitalized during the follow
      up for an average of 2.9 times. Neural tube defect (NTD) is a disabling problem,
      with operations, rehospitalizations and other costly treatments. Maternal
      education regarding preconceptional FA use/fortification of food with FA and
      appropriate guidance to the family with prenatal diagnosis will decrease the
      incidence and burden of the disease. 

PMID- 24292028
TI  - Short- and long-term effects of individualized enteral protein supplementation in
      preterm newborns.
AB  - The aim of this retrospective study was to assess the need for additional enteral
      protein supplementation in preterm newborns with gestational age (GA) <=32 weeks
      after full enteral feeds with either fortified breast milk (FBM) or preterm
      formula (PF) were reached, and to determine the effects of additional protein on
      physical and neurological development. After the standard early total parenteral
      nutrition (TPN) and reaching full enteral nutrition with 150-160 ml/kg/day,
      preterms were assessed for the requirement of additional protein based on serum
      blood urea nitrogen (BUN)/prealbumin levels. Additional enteral protein was given
      for BUN <5 mg/dl and/or prealbumin <=8 mg/dl with weekly assessments as per
      Neonatal Intensive Care Unit (NICU) protocol. Growth in the NICU and
      neurodevelopmental outcome at 18 months' corrected age (CA) were determined.
      There were 32 newborns in the non-supplemented group (Group 1) and 33 newborns in
      the supplemented group (Group 2). All newborns in Group 2 were on FBM. Weight
      gain and head growth were better and Bayley scores at 18 months' CA were higher
      in Group 2. Standard preterm nutrition with FBM may not be sufficient for
      preterms, and additional enteral protein supplementation may improve the physical
      growth rate in the NICU and result in better neurodevelopmental outcome at 18
      months' CA. 

PMID- 24292029
TI  - Impact of maternal vitamin D status during pregnancy on neonatal vitamin D
      status.
AB  - Maternal vitamin D deficiency is not uncommon. The lack of vitamin D during
      pregnancy may result in poor fetal growth and altered neonatal development that
      may persist into later life. Recognition of risk factors and early detection of
      vitamin D deficiency during pregnancy are important in order to prevent neonatal
      vitamin D deficiency and related complications. The aim of the current study was
      to assess the effect of maternal vitamin D status on the neonatal vitamin D
      stores. A total of 92 pregnant women at the end of the 3rd trimester and their
      newborns were recruited from Zagazig University Maternity and Children's
      Hospital, Egypt during the year 2011. Maternal and cord blood samples were taken
      at the beginning of the third trimester for determination of serum levels of
      circulating 25-hydroxyvitamin D3 (25(OH) D3) concentration, serum calcium (Ca++),
      phosphorus (PO4), and alkaline phosphatase (ALP). Compared with pregnant women
      with adequate vitamin D levels, women deficient in vitamin D had infants with
      vitamin D deficiency (X+/-SD 33.44+/-18.33 nmol/L vs. 55.39+/-17.37 nmol/L,
      p=0.01). Maternal and neonatal serum 25(OH)D3 levels showed a positive
      correlation with serum Ca++ and negative correlation with serum PO4 and ALP.
      Neonatal 25(OH) D3 was related to maternal third trimester levels (r=0.89,
      p=0.01). The newborn serum 25(OH)D3 concentrations are reliant on maternal
      vitamin D status, and the poor maternal vitamin D status may adversely affect
      neonatal vitamin D status and consequently Ca++ homeostasis. 

PMID- 24292030
TI  - Liposomal amphotericin B versus pentavalent antimony salts for visceral
      Leishmania in children.
AB  - The aim of this study was to investigate the efficacy of a 21-day schedule of
      liposomal amphotericin B compared to pentavalent antimony salts in the treatment
      of patients during a first episode of visceral leishmaniasis. In this study, 17
      cases of visceral leishmaniasis admitted to Behcet Uz Children's Hospital between
      January 2005 and April 2012 were reviewed retrospectively. The study group was
      composed of 11 males (64.7%) and 6 females (35.3%). One group included 11
      patients who were treated with pentavalent antimony salts, sodium stibogluconate
      or meglumine antimoniate, intramuscularly for 28 days. The second group was
      treated with amphotericin B intravenously at a dosage of 3 mg/kg on days 1-5, 10
      and 21 (a cumulative dose of 21 mg/kg/day). While pentavalent antimony salts were
      found to increase biochemical and hematological findings, liposomal amphotericin
      B was responsible for rapid recovery in fever and shorter hospital stay. As a
      result, our study shows the advantages of both medications independent of their
      costs. 

PMID- 24292031
TI  - Monitoring and prognostic evaluation of patients with congenital hypothyroidism
      treated in a pediatric endocrinology unit.
AB  - In this study, the etiological factors, diagnostic approaches, dose, and duration
      of treatment were compared between cases with transient and permanent congenital
      hypothyroidism (CH) with respect to prognosis. One hundred and twenty-two
      patients who received treatments with the diagnosis of CH in the last 10 years
      were included in the study. The records of the patients were reviewed
      retrospectively. Serum thyroid- stimulating hormone (TSH) levels at the time of
      diagnosis were found to be significantly higher, and total thyroxine (TT4) levels
      were found to be significantly lower in the permanent CH group in comparison to
      the transient CH group. A statistically significant difference was present
      between the groups regarding treatment doses, the time needed for TSH decrease to
      <5 mIU/ml and the TSH and free thyroxine (FT4) levels obtained one month after
      discontinuation of the treatment. The association between age at the time of
      initiation of treatment and results of Denver Developmental Test was noted to be
      statistically significant. The high frequency of transient CH in our region leads
      to the result that some of the patients had to be unnecessarily treated with L
      thyroxine for a long time. 

PMID- 24292032
TI  - Psychosocial status and quality of life in mothers of infants with colic.
AB  - We aimed to measure the psychosocial status and quality of life in mothers of
      babies with infantile colic (IC). Mothers and their newborns were stratified into
      Group 1 (colicky infant-mother dyad [n: 39]) and Group 2 (non-colicky infant
      mother dyad [n: 39]). Maternal symptoms of depression and anxiety were assessed
      using the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory
      (STAI), respectively. The Short Form-36 (SF36) was used to measure quality of
      life. Mean BDI score in Group 1 (14.7 +/- 12.9) was significantly higher than in
      Group 2 (7.7 +/- 5.5) (p=0.020). Mothers in Group 1 had lower Short Form- 36
      physical functioning (26.6 +/- 4.3 vs. 28.7 +/- 2.6; p=0.010) and social
      functioning (7.4 +/- 2.5 vs. 8.9 +/- 3.2, p=0.024) domain scores. Infantile colic
      (IC) was associated with higher maternal depression symptom scores and lower
      quality of life scores. As such, we think that mothers who have babies with IC
      should be closely monitored.

PMID- 24292033
TI  - Intralesional bleomycin sclerotherapy in childhood lymphangioma.
AB  - This clinical trial was conducted to evaluate the efficacy of intralesional
      bleomycin sclerotherapy (IBS) in children with lymphangioma and to determine the
      incidence of complications in the treatment. Seventeen lymphangioma cases were
      treated with IBS from 2004 to 2012. Age, mode of presentation, locations and
      types of lesions, and results of treatment were studied. Lymphangioma was
      diagnosed by physical examination and imaging studies. Most of the lesions were
      located in the cervical region (n=8) and of macrocystic type (n=13). After the
      first injection, three patients were lost to follow-up. Good response was seen in
      50% of the lesions, complete resolution in 35.7%, and poor response in 14.3%. No
      serious complications or side effects were observed after IBS. The average follow
      up was 18.5 months. IBS is effective in the treatment of lymphangioma. Although
      no major adverse effects have been encountered, complications should be kept in
      mind and in the event of their occurrence be treated immediately. 

PMID- 24292034
TI  - Improvement in cardiac structure and functions early after transcatheter closure
      of secundum atrial septal defect in children and adolescents.
AB  - We sought to assess the effects of transcatheter closure of atrial septal defect
      (ASD) on right and left ventricular form and functions, as well as atrial volumes
      and pulmonary venous flows. We enrolled 25 patients (mean age: 9.02)
      prospectively who underwent successful transcatheter closure of secundum ASD. We
      performed transthoracic echocardiography, including two-dimensional, pulsed wave
      Doppler, M-mode echocardiography, and tissue Doppler imaging before the procedure
      and 1 day, 1 month, 3 months and 6 months after the procedure. Serum brain
      natriuretic peptide (BNP) levels were measured prior to the procedure, and 1 day,
      1 month, and 3 months there after. Mitral inflow early diastolic wave increased
      significantly, while isovolumetric relaxation time and deceleration time did not
      change during the follow-up. The E/E' was also increased significantly during
      follow-up. After the closure, right ventricular size and right atrial volume
      reduced, while left ventricular size increased significantly. There was a
      statistically significant improvement in left and right ventricular Tei indices.
      Pulmonary vein systolic velocity and the ratio of systolic to diastolic wave
      decreased, while atrial reversal wave (ARW) velocity increased immediately after
      the procedure. Although the concentration of BNP was increased on the first day
      after the procedure, its levels reduced and had reached the pre-procedure values
      at 1 month of follow-up. In the study, a significant improvement in the right and
      left ventricular functions was detected after transcatheter closure of secundum
      ASD in the short-term follow-up. In addition, we found a significant reduction in
      right heart sizes with corresponding global functional improvement in the right
      ventricle after the procedure.

PMID- 24292035
TI  - Reactive thrombocytosis in children.
AB  - The aim of this study was to evaluate the causes of thrombocytosis, which was
      defined as a platelet count greater than 500 x 10(9)/L, and to compare the groups
      with mild and severe thrombocytosis. A total of 484 patients were evaluated for
      the etiology of thrombocytosis. Patients with a platelet count between 500-800 x
      10(9)/L were considered to have mild thrombocytosis, while those with a count of
      >=800 x 10(9)/L were considered as having severe thrombocytosis. Of 484 patients
      included, 63% had thrombocytosis due to an infectious disease, 11.4% had a
      chronic inflammatory condition, 8.5% had anemia, and 5.2% had tissue injury. The
      frequency of chronic inflammation was higher in the severe thrombocytosis group
      compared to the mild thrombocytosis group (p=0.006). In conclusion, severe
      infections and chronic inflammatory conditions should be considered in the
      differential diagnosis of a patient with severe thrombocytosis.

PMID- 24292036
TI  - Possible internet addiction in high school students in the city center of Isparta
      and associated factors: a cross-sectional study.
AB  - The aim of the present study was to detect both sociodemographic factors related
      to possible Internet addiction and the prevalence of this addiction, as well as
      to determine the relationship between possible Internet addiction and self
      injurious behavior, life satisfaction, and the level of loneliness in adolescents
      attending high school in the city center of Isparta. A cross-sectional analytic
      study was planned for high school adolescents. An information form concerning
      Internet usage and related sociodemographic factors, Internet Addiction Scale,
      Satisfaction with Life Scale, and a UCLA Loneliness Scale- Short Form were
      applied to the students. The prevalence of possible Internet addiction was found
      to be 14.4%. Adolescents with possible Internet addiction were found to have low
      levels of loneliness and high levels of life satisfaction. The results are then
      discussed in light of the related literature. 

PMID- 24292037
TI  - Fulminant pertussis in very young infants: two cases and review of the
      literature.
AB  - Pertussis is one of the leading causes of death that can be prevented by
      vaccination. More than 600,000 deaths from pertussis occur annually, with a
      disproportionate number appearing in unvaccinated infants. Pertussis is
      particularly troublesome because it does not necessarily present itself in its
      commonly known classical stages. Therefore, in very young and non-immunized
      children, the disease may have a fulminant process characterized by severe
      leukocytosis, neurologic involvement and serious cardiopulmonary failure that can
      be accompanied by pulmonary hypertension, persistent hypoxia and death. This
      article describes two infants with fulminant pertussis; they were admitted for
      acute respiratory failure and severe leukocytosis and ultimately died from multi
      organ failure. 

PMID- 24292038
TI  - A case of glandular tularemia presenting with prolonged fever and mesenteric
      lymphadenopathy.
AB  - Tularemia is a zoonotic disease caused by Francisella tularensis, a gramnegative
      coccobacillus that is transmitted to humans by direct contact with or ingestion
      of infected animal tissues, through the bite of infected arthropods, by
      consumption of contaminated food or water, or from inhalation of aerosolized
      bacteria. Presented herein is a case of a four-year-old girl who was diagnosed
      with glandular tularemia after presenting with prolonged fever and mesenteric
      lymphadenopathy. A history of contact with a rabbit was a valuable clue for the
      diagnosis. 

PMID- 24292039
TI  - Prematurity due to maternal brucella infection and review of the literature.
AB  - Brucellosis is a zoonosis caused by ingestion of unpasteurized milk or other
      dairy products from infected animals or through close contact with their
      secretions. Human-to-human transmission, which is rare, has been reported in
      association with blood transfusion, bone marrow transplantation, transplacental
      or perinatal exposure, and breastfeeding. In the neonatal period, congenital
      brucellosis, which is an extremely rare condition, can lead to serious clinical
      consequences with a high morbidity and mortality rate. The case presented here is
      a premature baby born at 25 weeks' gestation to a mother suffering from severe
      oligohydramnios, premature rupture of membranes and untreated acute brucellosis.
      The baby had severe respiratory distress and radiological findings compatible
      with pulmonary infection. The blood cultures of the baby and the mother were
      positive for Brucella melitensis, supporting the diagnosis of brucellosis with
      presumed transplacental transmission. 

PMID- 24292040
TI  - Late neonatal hypocalcemic tetany as a manifestation of unrecognized maternal
      primary hyperparathyroidism.
AB  - Maternal primary hyperparathyroidism causing hypercalcemia during pregnancy can
      suppress fetal and neonatal parathyroid hormone secretion. We report a newborn
      with transient hypoparathyroidism presented by hypocalcemic seizure and tetany on
      the 21st postnatal day in whom the final diagnosis was asymptomatic maternal
      primary hyperparathyroidism. Neonatal hypocalcemia usually occurs early in life
      in infants of maternal primary hyperparathyroidism, and although it is very rare,
      further investigation for unexplained late-onset hypocalcemia may reveal this
      diagnosis. 

PMID- 24292041
TI  - Acute cerebellar ataxia associated with enteric fever in a child: a case report.
AB  - Enteric fever is a common infectious disease of the tropical world.
      Characteristic presenting features include fever, relative bradycardia, diarrhea
      or constipation, and abdominal pain. Central nervous system involvement is not
      rare and has a wide spectrum of presentation in enteric fever. Complications such
      as meningism, delirium, coma, and convulsions have been reported often. However,
      isolated acute cerebellar ataxia associated with enteric fever is rare. Here, we
      report a seven-year-old boy with enteric fever who presented with acute
      cerebellar ataxia. Following treatment with appropriate antibiotics, the patient
      showed complete recovery over the next four weeks. 

PMID- 24292042
TI  - A girl with steroid cell ovarian tumor misdiagnosed as non-classical congenital
      adrenal hyperplasia.
AB  - Ovarian steroid cell tumors are rarely encountered in prepubertal girls. The
      majority of these tumors produce hormones, testosterone being the leading one.
      These tumors may either coexist with or imitate congenital adrenal hyperplasia
      (CAH). We present a 13-year-old female patient who was diagnosed with non
      classical CAH at six years of age while being investigated for premature
      pubarche. She was diagnosed with steroid cell ovarian tumor after a delay of six
      years. The diagnosis was based on radiologic imaging, which was performed to
      investigate causes of unsuccessful metabolic control while under high-dose
      steroid therapy. The right ovarian hypoechoic mass of 23x22 mm was excised
      laparoscopically, preserving the ovary. Immunohistochemical staining showed that
      tumor cells were strongly positive with inhibin and focally positive with
      vimentin. Based on these findings, the patient was diagnosed with ovarian steroid
      cell tumor not otherwise specified. In the postoperative second week, total
      testosterone level was <10 ng/ml, and 17 hydroxyprogesterone (17-OHP) level was
      1.1 ng/ml. Peak 17-OHP level was 4.2 ng/ml on repeated ACTH stimulations, and the
      diagnosis of CAH was excluded. Steroid therapy was tapered down and then
      discontinued. It should be kept in mind that there may be a misdiagnosis in cases
      of CAH, which may present itself with unsuccessful metabolic control even while
      under the appropriate treatment dose. Early diagnosis and treatment would prevent
      the development of irreversible signs. 

PMID- 24292043
TI  - Aggressive giant cystic lymphatic malformation in a newborn.
AB  - Lymphatic malformations are uncommon, benign and congenital malformations of the
      lymphatic system exhibiting lack of development of communication between the
      lymphatic and venous circulation. We report the unusual case of rapidly expanding
      giant lymphatic malformation of the torso, bilateral axillae and left upper
      extremity of a newborn. As the first-line treatment, aspiration and sclerotherapy
      with bleomycin were performed. The sclerotherapy failed to cause regression of
      the mass, and rapid expansion of the malformation necessitated surgery. Partial
      resection of the mass was performed. Clinical symptoms of respiratory distress
      resolved in the early postoperative period, and the patient became
      hemodynamically stable. However, intrathoracic invasion of the mass developed,
      leading to restriction of thoracic expansion, ending in death. In conclusion,
      surgical treatment of giant lymphatic malformations remains challenging. 

PMID- 24292044
TI  - Laparoscopic detorsion of isolated idiopathic fallopian tube torsion:
      conservative treatment in a 13-year-old girl.
AB  - Isolated fallopian tube torsion (IFTT) is a rare entity in adolescent girls.
      Invasive surgery, salpingectomy, was used during the initial surgery or at the
      time of recurrent torsion in 87% of previously reported cases. Herein, the
      authors present an adolescent premenarcheal girl with idiopathic IFTT, which was
      treated by laparoscopic detorsion, to emphasize that tubal torsion should be
      included in the list of differential diagnoses of abdominal pain in adolescent
      girls. Minimally invasive, organ-saving surgery should be done, and the child
      should be followed up for recurrent torsion. 

PMID- 24292046
TI  - Fat necrosis of transverse colon and necrotizing pancreatitis in a patient with
      acute lymphoblastic leukemia (ALL): cause of massive ascites and high fever.
AB  - We report a nine-year-old boy with acute lymphoblastic leukemia L3 (ALL-L3) and
      necrotizing pancreatitis in which necrosis was not limited to the pancreas. As
      our patient had a defective inflammatory process as a result of underlying
      malignant disease and neutropenia, the peripancreatic collection could not be
      limited and no pseudocyst was formed. In our patient, the unlimited inflammatory
      process and pancreatic secretions infiltrated the transverse mesocolon and
      transverse colon, leading to fat necrosis of the transverse colon, causing
      massive ascites and high fever. As there was no response to medical treatment,
      the success was achieved only by surgical resection. The infiltration of
      surrounding tissue and nearby organs by inflammation and fat necrosis in
      necrotizing pancreatitis has not been reported previously in a pediatric patient.

PMID- 24292047
TI  - Failure or delay in diagnosing Fanconi anemia--a well-defined genetic disorder.

PMID- 24292045
TI  - Posterior reversible encephalopathy syndrome due to pulse methylprednisolone
      therapy in a child.
AB  - Posterior reversible leukoencephalopathy syndrome (PRES) is a recently described
      disorder with typical radiological findings of bilateral grey and white matter
      abnormalities in the posterior regions of the cerebral hemispheres. It has been
      described in children in association with some medications, renal disease,
      autoimmune disease, transplantation, and sepsis. In this report, we discuss an
      eight-year-old boy with PRES during pulse methylprednisolone therapy. In
      conclusion, PRES is a neurological complication of pulse methylprednisolone
      therapy, which responds favorably to prompt therapy withdrawal and blood pressure
      control. 

PMID- 24292048
TI  - Neuropharmacologic studies on the brain serotonin1A receptor using the selective
      agonist osemozotan.
AB  - Alterations in serotonin (5-HT) neurochemistry have been implicated in the
      etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders,
      depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated
      through 14 receptor subtypes, and those receptors, including the 5-HT1A receptor,
      are considered to be potential targets for the treatment of psychiatric
      disorders. We developed the novel 5-HT1A receptor agonist MKC-242 (called
      osemozotan) and characterized its neurochemical and pharmacological profiles. 5
      HT1A receptor agonists modulate the release of amine neurotransmitters through
      the activation of presynaptic or postsynaptic 5-HT1A receptors in the brain. The
      agonist has antianxiety and antidepressant effects and improves abnormal
      behaviors such as aggressive behavior and deficits of prepulse inhibition in
      isolation-reared mice. We also demonstrated that spinal 5-HT1A receptor
      activation is involved in isolation rearing-induced hypoalgesia. Concerning the
      mechanism for induction of isolation-induced abnormal behaviors, we have recently
      found that the raphe-prefrontal 5-HT system plays a key role in encounter
      stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we
      showed that osemozotan attenuates psychostimulant-induced behavioral
      sensitization and that prefrontal dopamine release is enhanced by functional
      interaction between the 5-HT1A receptor and other receptors. This review
      summarizes the neuropharmacology of the 5-HT1A receptor, focusing on our studies
      using osemozotan, and suggests that the 5-HT1A receptor may be a target molecule
      for the treatment of psychiatric disorders, pain, and drug dependence. 

PMID- 24292049
TI  - Quantitative evaluation of initial symptoms as predictors to detect adverse drug
      reactions using Bayes' theory: expansion and evaluation of drug-adverse drug
      reaction-initial symptom combinations using adverse event reporting system
      database.
AB  - In prescription dispensing in Japan, to avoid adverse drug reactions (ADR)
      pharmacists provide patients with information concerning the initial symptoms
      (IS) of any ADR that might be caused by the drugs they have been prescribed.
      However, the usefulness of such information for preventing ADR has not been
      quantitatively evaluated. We previously performed a trial calculation of the
      usefulness of rash as a predictor of drug-induced liver disorders by applying
      Bayes' theorem and showed that the predictive utility of IS can be quantitatively
      evaluated using likelihood ratios. However, for other drug-ADR-IS combinations it
      was difficult to obtain the information required for the calculations from
      Japanese data alone. In this study, using the Adverse Event Reporting System
      (AERS) database of the U.S. Food and Drug Administration (FDA), we evaluated 132
      drug-ADR-IS combinations that were considered to be potentially clinical
      significant. Regarding bezafibrate-associated rhabdomyolysis and cibenzoline
      associated hypoglycemia, these ADR were not detected in cases involving
      monotherapy. For 58 combinations, no events that were considered to be IS of the
      target ADR developed. Fever, nausea, and decreased appetite were the IS of many
      ADR, making them very useful predictors. In contrast, pruritus and rash were not
      very useful. Fever might be a predictor of thiamazole-induced agranulocytosis or
      levofloxacin- or terbinafine-induced liver disorder, tremors might be useful for
      predicting paroxetine-induced serotonin syndrome, and decreased appetite might be
      a useful indicator of terbinafine-induced liver dysfunction. 

PMID- 24292050
TI  - Effect of polyphenols on 3-hydroxy-3-methylglutaryl-coenzyme A lyase activity in
      human hepatoma HepG2 cell extracts.
AB  - When carbohydrate metabolism is impaired, fatty acid metabolism is activated.
      Excess acetyl-coenzyme A (CoA) is generated from fatty acids by beta-oxidation
      and is used for the formation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) and
      subsequently for acetoacetate. High levels of secreted ketone bodies
      (acetoacetate and 3beta-hydroxybutyrate) lower the pH of blood and urine,
      resulting in ketoacidosis. HMG-CoA lyase in hepatic cells is a rate-limiting
      enzyme catalyzing the cleavage of HMG-CoA to acetoacetate, and thus inhibition of
      this enzyme results in reduced acetoacetate production, in other words, impaired
      ketoacidosis. Inhibition of HMG-CoA lyase activity possibly prevents ketoacidosis
      and should be the therapeutic target. Polyphenols are common and abundant dietary
      constituents with beneficial effects on human health. We examined the inhibitory
      effects of dietary polyphenols on HMG-CoA lyase activity in cellular extracts of
      human hepatoma HepG2 cells. Of the nine representative dietary polyphenols
      tested, (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), and
      gallic acid (GA) effectively inhibited HMG-CoA lyase activity. Lineweaver-Burk
      analysis revealed that EGC and EGCG are likely to be mixed-type noncompetitive
      inhibitors. Pyrogallol with the gallyl structure also inhibited HMG-CoA lyase
      activity, suggesting that the gallyl moiety of polyphenols is important for the
      inhibition of HMG-CoA lyase activity. 

PMID- 24292051
TI  - Neuroprotective effect of trans-cinnamaldehyde on the 6-hydroxydopamine-induced
      dopaminergic injury.
AB  - The anti-inflammatory and neuroprotective effects of trans-cinnamaldehyde (TCA)
      were investigated on the inflammatory cells and the dopaminergic degeneration in
      mice. TCA inhibited the up-regulation of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-induced inflammatory
      BV2 microglial cells. To investigate the TCA efficacy on the 6-hydroxydopamine (6
      OHDA)-induced dopaminergic degeneration in mice, an intracerebroventricular
      injection of 6-OHDA was given to the mice, and TCA (30 mg/kg) was
      intraperitoneally administered. At 7 d after the 6-OHDA injection, 6-OHDA led to
      a severe loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the
      striatum and substantia nigra (SN). On the other hand, TCA dramatically
      maintained the number of TH-positive dopaminergic neurons in the striatum and SN
      regions of the 6-OHDA-treated mice, which indicates that TCA is able to inhibit
      the 6-OHDA-induced reduction of TH expression in the dopaminergic neurons in the
      striatum and SN regions. TCA also inhibited the induction of iNOS and COX-2 in
      the 6-OHDA model, similarly as shown in the LPS-induced inflammatory BV2
      microglial cells. These results indicate that TCA has a neuroprotective effect on
      dopaminergic neurons and that this effect may be associated with the inhibition
      of inflammatory responses. These findings suggest that TCA may be a therapeutic
      candidate for the prevention of inflammation-mediated neurodegenerative diseases.

PMID- 24292052
TI  - Comparison of inhibitory duration of grapefruit juice on organic anion
      transporting polypeptide and cytochrome P450 3A4.
AB  - Recently, a new type of interaction has been reported in which fruit juices
      diminish oral drug bioavailability through inhibition of organic anion
      transporting polypeptide (OATP). In this study, we aimed to clarify the duration
      of OATP inhibition by grapefruit juice (GFJ), and to compare it with the duration
      of GFJ-induced inhibition of cytochrome P450 (CYP) 3A4 activity. Seven healthy
      volunteers were enrolled in this open-label, single-sequence study. They were
      orally administered celiprolol (100 mg) and midazolam (15 ug/kg) with water on
      the control day. Three days later, they ingested GFJ (200 mL) 3 times a day for 3
      d. On day 1, the same drugs were administered with GFJ. On days 3 and 7, the same
      drugs were administered with water. Pharmacokinetics of both drugs were evaluated
      on each trial day. The peak plasma concentration (Cmax) and the area under the
      plasma concentration-time curve from 0 to 8 h (AUC0-8) of celiprolol
      significantly decreased on day 1, and the mean ratios of these values and the
      corresponding control-day values were 0.18 and 0.25, respectively. The Cmax and
      AUC0-8 returned to the control levels on days 3 and 7. In contrast, AUC0-8 of
      midazolam were higher on days 1 and 3 than on the control day (mean ratio, 2.12
      and 1.47, respectively). The AUC0-8 returned to the control level on day 7. In
      conclusion, results of this study indicated that the OATP inhibition caused by
      GFJ dissipated faster than GFJ-mediated alterations in CYP3A4 activity, which
      were sustained for at least 48 h. 

PMID- 24292053
TI  - Characterization of protamine uptake by opossum kidney epithelial cells.
AB  - Protamine, a mixture of polypeptides that is rich in arginine, has been used
      clinically as an antidote to heparin overdoses and a complexing agent in a long
      acting insulin preparation. When protamine is administered intravenously, its
      abundant accumulation in the kidneys has been reported. However, the renal uptake
      mechanism for protamine is not clear. In this study, we examined the transport
      mechanism for protamine in opossum kidney (OK) cells, a suitable in vitro model
      for renal proximal tubular epithelial cells. Flow cytometric analysis revealed
      that the association of fluorescein isothiocyanate (FITC)-labeled protamine from
      salmon (FITC-protamine) by OK cells was inhibited by unlabeled protamine in a
      concentration-dependent manner. The association of FITC-protamine was temperature
      and energy-dependent. Confocal microscopy analysis showed that the fluorescence
      was localized in the cytoplasm and nucleus of OK cells. In addition, FITC
      protamine association was inhibited by cationic drugs such as polycationic
      gentamicin and polymixin B, but it was increased by a basic amino acid, arginine.
      Inhibitors for clathrin- and caveolin-dependent endocytosis showed inhibitory
      effects on FITC-protamine association. Pretreatment with heparinase III partially
      but significantly decreased the association of FITC-protamine. These results
      suggest that protamine may be taken up by OK cells via receptor-mediated
      endocytosis, which may result in its localization in the cytoplasm and nucleus of
      the cells. 

PMID- 24292054
TI  - Prediction of in vivo carbamazepine 10,11-epoxidation from in vitro metabolic
      studies with human liver microsomes: importance of its sigmoidal kinetics.
AB  - Hepatic intrinsic clearance (CLint) of drugs is often predicted based on in vitro
      data that are obtained from the Michaelis-Menten analysis. While most of the
      metabolic rate-substrate concentration kinetic curves fit to the Michaelis-Menten
      equation, cytochrome P450 (CYP) and uridine 5'-diphosphate (UDP)
      glucuronosyltransferases exhibit sigmoidal kinetics for certain drugs. In our
      study, the kinetics of CYP3A4-catalyzed carbamazepine 10,11-epoxidation in human
      liver microsomes was sigmoidal and fitted to the Hill equation, revealing the S50
      value of 358 uM, n of 2.0, and the Vmax value of 463 pmol/min/mg. While the
      intrinsic clearance calculated from Michaelis-Menten parameters (CLint)
      overestimated the observed in vivo intrinsic clearance (CLint, in vivo), the
      maximum intrinsic clearance calculated based on the Hill equation (CLmax)
      exhibited better predictions of CLint, in vivo. Such better prediction using the
      CLmax was also observed for other four drugs, all of which also exhibited
      sigmoidal metabolic rate-concentration curves, according to the literature data.
      However, even if we assume such Hill equation, intrinsic clearances predicted at
      their therapeutic concentrations from in vitro data were still much lower than
      their CLint, in vivo, suggesting the existence of unknown factors causing
      discrepancy between in vitro intrinsic clearance in human liver microsomes and in
      vivo data. Thus, even if we assume sigmoidal kinetics, that would not be enough
      for accurate prediction of CLint, in vivo, and it would be preferable to use
      CLmax to quantitatively extrapolate the in vitro data to in vivo clearance. 

PMID- 24292055
TI  - Development of a specific and sensitive enzyme-linked immunosorbent assay for the
      quantification of imatinib.
AB  - Imatinib is an oral tyrosine kinase inhibitor used for first-line treatment of
      chronic myeloid leukemia. Therapeutic drug monitoring targeting trough plasma
      levels of about 1000 ng/mL may help to optimize imantinib's therapeutic effect.
      This paper reports a specific and sensitive enzyme-linked immunosorbent assay
      (ELISA) for a pharmacokinetic evaluation of imatinib. Anti-imatinib antibody was
      obtained by immunizing rabbits with an antigen conjugated with bovine serum
      albumin and succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. Enzyme
      labeling of imatinib with horseradish peroxidase was similarly performed using
      succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. A simple ELISA for
      imatinib was developed using the principle of direct competition between imatinib
      and the enzyme marker for anti-imatinib antibody which had been adsorbed by the
      plastic surface of a microtiter plate. Serum imatinib concentrations lower than
      40 pg/mL were reproducibly measurable using the ELISA. This ELISA was specific to
      imatinib and showed very slight cross-reactivity (1.2%) with a major metabolite,
      N-desmethyl imatinib. Using this assay, drug levels were easily measured in the
      blood of mice after their oral administration of imatinib at a single dose of 50
      mg/kg. The specificity and sensitivity of the ELISA for imatinib should provide a
      valuable new tool for use in therapeutic drug monitoring and pharmacokinetic
      studies of imatinib. 

PMID- 24292056
TI  - Supplementary seleno-L-methionine suppresses active cutaneous anaphylaxis
      reaction.
AB  - To clarify the relationship between selenium supplementation and type I allergic
      reaction, we investigated the effect of seleno-L-methionine (SeMet)
      supplementation on the active cutaneous anaphylaxis (ACA) reaction and cytokine
      production in splenocytes. Female BALB/c mice were sensitized by intraperitoneal
      injection of ovalbumin (OVA), and SeMet was administered orally for 2 weeks
      followed by a challenge with OVA to induce an ACA reaction. SeMet supplementation
      suppressed the ACA reaction in a dose-dependent manner. Plasma OVA-specific
      immunoglobulin E (IgE) level was strongly inhibited in SeMet-supplemented mice
      compared with control mice. The mRNA expression levels of the T helper 2 (Th2)
      cytokines interleukin (IL)-4 and IL-13 in the spleen of SeMet-supplemented mice
      were lower than those in control mice. The mRNA expression level of a Th1
      cytokine, interferon (IFN)-gamma, in the spleen of SeMet-supplemented mice was
      higher than that in control mice. Splenocytes restimulated with OVA in vitro from
      SeMet-supplemented mice produced lower amounts of IL-4 and IL-13 than those of
      control mice and higher amounts of IFN-gamma than those from the control mice.
      These results suggest that oral SeMet supplementation suppresses OVA-induced ACA
      reaction by lowered Th2 cytokine production and augmenting Th1 cytokine
      production. 

PMID- 24292057
TI  - Improvement of depression-like behavior and memory impairment with the ethanol
      extract of Pleurotus eryngii in ovariectomized rats.
AB  - Ethanol extract of Pleurotus eryngii (DC.) QUEL has estrogen-like activities that
      protect against bone loss caused by estrogen deficiency. In the present study, we
      investigated the effect of P. eryngii on depression-like behavior and memory
      impairment in ovariectomized (OVX) rats. Immobility time during a forced swimming
      test was significantly longer for OVX rats than for sham-operated rats. The
      depression-like behavior in OVX rats was improved by long-term administration of
      the ethanol extract of P. eryngii (500 mg/kg body weight (b.w.)/d). Spatial
      memory impairment in OVX rats assessed by the Morris water maze test was also
      improved by P. eryngii extract without any effect on motility. These results
      suggested that P. eryngii extract has estrogen-like improvement activity against
      depression-like behavior and memory impairment in OVX rats. Additionally,
      increase in the amount of synaptosomal zinc after ovariectomy was inhibited by P.
      eryngii extract. Since zinc in synaptic vesicles is important for memory function
      and is linked to the pathophysiology of depression, normalization of zinc
      signaling would be involved in the beneficial effect of P. eryngii extract on
      neurological disorders after ovariectomy. 

PMID- 24292058
TI  - Niflumic acid activates additional currents of the human glial L-glutamate
      transporter EAAT1 in a substrate-dependent manner.
AB  - The astrocytic L-glutamate (L-Glu) transporter EAAT1 participates in the removal
      of L-Glu from the synaptic cleft and maintenance of non-toxic concentrations in
      the extracellular fluid. We have shown that niflumic acid (NFA), a non-steroidal
      anti-inflammatory drug (NSAIDs), alters L-Glu-induced EAAT1 currents in a voltage
      dependent manner using the two-electrode voltage clamp technique in Xenopus
      oocytes expressing EAAT1. In this study, we characterised the effects of NFA on
      each type of ion-flux through EAAT1. NFA modulated currents induced by both L-Glu
      and L-aspartate (L-Asp) in a voltage-dependent manner. Ion-substitution
      experiments revealed that the activation of additional H(+) conductance was
      involved in the modulation of currents induced by L-Asp and L-Glu, but Cl(-) was
      involved only with the L-Asp currents. NFA activated additional currents of EAAT1
      in a substrate-dependent manner. 

PMID- 24292059
TI  - Senescence marker protein-30/gluconolactonase expression in the mouse ovary
      during gestation.
AB  - Senescence marker protein-30 (SMP30) was first described as a physiologic entity
      that decreases in the rat liver and kidney with aging. Previously, we established
      that SMP30 is the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is
      involved in ascorbic acid (AA) biosynthesis. In the present study, we found
      SMP30/GNL mRNA expressed in the mouse ovary. To ascertain the reason for ovarian
      SMP30/GNL expression, we examined mice during gestation. SMP30/GNL mRNA
      expression was evident at the start of gestation, increased for the next eight
      days then decreased rapidly. Moreover, L-gulono-gamma-lactone oxidase (Gulo)
      mRNA, which catalyzes the last step of AA, was found in the ovaries of these
      mice. The variations of these genes' expression showed an inverse pattern to that
      of Cyp19a1 (aromatase) mRNA expression. Therefore, the SMP30/GNL and Gulo mRNA
      expression might be regulated by estrogen levels in the ovary. Since the presence
      of both SMP30/GNL and Gulo mRNAs could indicate that AA synthesis occurs in the
      ovary, we quantified AA levels in mouse ovaries during gestation. However, no
      correlation was found between changes of AA content and SMP30/GNL or Gulo mRNAs
      expression at this site. Moreover, we compared the changes of AA content during
      gestation between wild-type and SMP30/GNL knockout mice, which cannot synthesize
      AA, and found no significant differences between them. These results indicated
      that, although AA synthesis might occur in the ovaries, the amount of AA which is
      synthesized in ovaries must be quite low and insufficient to influence the AA
      content in ovary. 

PMID- 24292060
TI  - Reduced plasma glucose by asparagine synthetase knockdown in the mouse liver.
AB  - Expression of the asparagine synthetase gene is dependent on extracellular
      glucose concentration. This gene was knocked-down in livers of male Balb/c mice
      by a hydrodynamic tail vein injection of small interfering RNA (siRNA) against
      the gene. This knockdown resulted in a significant decrease in plasma glucose
      concentration. These results suggested that asparagine synthetase is a novel
      protein that regulates plasma glucose levels. 

PMID- 24292061
TI  - Emulsification using highly hydrophilic surfactants improves the absorption of
      orally administered coenzyme Q10.
AB  - Coenzyme Q10 (CoQ10) is an essential component in the electron-transport systems
      of mitochondria and bacteria and is often used as a supplementary treatment for
      some diseases. We previously reported that the bioavailability of CoQ10 powder
      was less than 10%. In this study, we investigated various preparations to improve
      the intestinal absorption of CoQ10 with focus on the effect of emulsification. We
      prepared a suspension and some emulsions with four types of surfactants and
      investigated the plasma concentration profile after oral administration to rats.
      The absorption of CoQ10 was improved by an emulsion formulation although there
      was little absorption of CoQ10 when a suspension was administered. However,
      little CoQ10 was absorbed in the bile duct-ligated group even when the emulsion
      formulation was administered (about 50% of the control group). Bile and emulsion
      formulation are essential for absorption of CoQ10. When the preparations
      containing Tween20 (polysorbate (20) sorbitan monolaurate) and Tween80
      (polyoxyethylene (20) sorbitan monooleate) were administered, plasma
      concentrations of CoQ10 were higher than those obtained with preparations
      containing Tween65 (polyoxyethylene (20) sorbitan tristearate) and Span20
      (sorbitan monolaurate). Tween20 and Tween80 have higher hydrophile-lipophile
      balance (HLB) values than those Tween65 and Span20. Our study suggests that
      highly lipophilic compounds like CoQ10 would diffuse the unstirred water layer
      and would easily access the intestinal apical membrane by an emulsion containing
      a surfactant with a high HLB value. Attention must be given to CoQ10
      supplementation for patients whose bile is not excreted to the intestine such as
      patients with cholestasis. 

PMID- 24292062
TI  - Induction of hepatocyte growth factor production in human dermal fibroblasts by
      caffeic acid derivatives.
AB  - Hepatocyte growth factor (HGF) has mitogenic, motogenic, and morphogenic
      activities in epithelial cells. Induction of HGF production may be involved in
      organ regeneration, wound healing and embryogenesis. In this study, we examined
      the effects of caffeic acid derivatives including 4,5-di-O-caffeoylquinic acid
      (1) and acteoside (2) on HGF production in Neonatal Normal Human Dermal
      Fibroblasts (NHDF). Both 4,5-di-O-caffeoylquinic acid (1) and acteoside (2)
      significantly induced HGF production dose-dependent manner. To know the important
      substructure for HGF production activity, we next investigated the effect of the
      partial structure of these caffeic acid derivatives. From the results, caffeic
      acid (3) showed strong activity on the promotion of HGF production, while
      hydroxytyrosol (4) and quinic acid (5) didn't show any activity. Our findings
      suggest that the caffeoyl moiety of caffeic acid derivatives is essential for
      accelerated production of HGF. The compound which has the caffeoyl moiety may be
      useful for the treatment of some intractable organ disease. 

PMID- 24292063
TI  - Superconducting fluctuations in organic molecular metals enhanced by Mott
      criticality.
AB  - Unconventional superconductivity typically occurs in materials in which a small
      change of a parameter such as bandwidth or doping leads to antiferromagnetic or
      Mott insulating phases. As such competing phases are approached, the properties
      of the superconductor often become increasingly exotic. For example, in organic
      superconductors and underdoped high-T(c) cuprate superconductors a fluctuating
      superconducting state persists to temperatures significantly above T(c). By
      studying alloys of quasi-two-dimensional organic molecular metals in the kappa
      (BEDT-TTF)2X family, we reveal how the Nernst effect, a sensitive probe of
      superconducting phase fluctuations, evolves in the regime of extreme Mott
      criticality. We find strong evidence that, as the phase diagram is traversed
      through superconductivity towards the Mott state, the temperature scale for
      superconducting fluctuations increases dramatically, eventually approaching the
      temperature at which quasiparticles become identifiable at all.

PMID- 24292064
TI  - Do the placental barrier, parasite genotype and Toll-like receptor polymorphisms
      contribute to the course of primary infection with various Toxoplasma gondii
      genotypes in pregnant women?
AB  - Toxoplasma gondii has a highly clonal genetic structure classified into three
      major genetic types, I, II, and III, plus additional recombinant and atypical
      strains. In humans, type I and atypical strains usually associate with severe
      toxoplasmosis. Type II strains, predominantly identified in European countries
      and the United States, correlate with a differential course of toxoplasmosis.
      During pregnancy, the important protective role of the placenta against maternal
      fetal T. gondii transmission has been reported. T. gondii preferentially
      colonizes extravillous trophoblasts as compared to syncytiotrophoblasts. The
      latter compartment was suggested to act as the real barrier to the fetal
      dissemination of T. gondii. Alterations in immune response to particular T.
      gondii strains were observed. Higher transcription levels of IP-10, IL-1beta, IL
      6, IL-10, IL-12 cytokines, and NF-kappaB translocation to the nucleus were more
      often documented for type II strains than type I strains. Since the induction of
      IL-12 during type II infection was Myd88-dependent, the involvement of Toll-like
      receptors (TLRs) in the immunity against these strains was suggested.
      Differential expression of TLRs depends on placental cell types and gestational
      age. The expression of TLR2 and TLR4 in the first trimester of pregnancy was
      reported only for villous cytotrophoblasts and extravillous trophoblasts, but not
      for syncytiotrophoblasts. The involvement of single-nucleotide polymorphisms
      (SNPs) in the TLR genes in infectious pathogenicity, including toxoplasmic
      retinochoroiditis, points at a possible involvement of TLR alterations in
      immunity against T. gondii. We conclude that studies on TLR contributions in the
      maternal-fetal transmission of particular parasite strains and congenital
      toxoplasmosis are warranted. 

PMID- 24292067
TI  - In vivo visualization of cells labeled with superparamagnetic iron oxides by a
      sub-millisecond gradient echo sequence.
AB  - OBJECT: In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic
      islets (PIs) transplanted into the liver is still challenging in humans. The aim
      of this study was to develop and evaluate a double contrast method for the
      detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles.
      MATERIALS AND METHODS: A double-echo three-dimensional (3D) spoiled gradient echo
      sequence was adapted to yield a sub-millisecond first echo time using variable
      echo times and highly asymmetric Cartesian readout. Positive contrast was
      achieved by conventional and relative image subtraction. Experiments for cell
      detection efficiency were performed in vitro on gelatin phantoms, in vivo on a
      Lewis rat and on a patient 6 months after PI transplantation. RESULTS: It was
      demonstrated that the proposed method can be used for the detection of
      transplanted PIs with positive contrast in vitro and in vivo. For all
      experiments, relative subtraction yielded comparable and in some cases better
      contrast than conventional subtraction. For the first time, positive contrast
      imaging of transplanted human PIs was performed in vivo in patients. CONCLUSION:
      The proposed method allows 3D data acquisition within a single breath-hold and
      yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic
      islets relative to negative contrast images, therefore providing improved
      identification.

PMID- 24292068
TI  - Glycocalyx engineering reveals a Siglec-based mechanism for NK cell
      immunoevasion.
AB  - The increase of cell surface sialic acid is a characteristic shared by many tumor
      types. A correlation between hypersialylation and immunoprotection has been
      observed, but few hypotheses have provided a mechanistic understanding of this
      immunosuppressive phenomenon. Here, we show that increasing sialylated glycans on
      cancer cells inhibits human natural killer (NK) cell activation through the
      recruitment of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7). Key
      to these findings was the use of glycopolymers end-functionalized with
      phospholipids, which enable the introduction of synthetically defined glycans
      onto cancer cell surfaces. Remodeling the sialylation status of cancer cells
      affected the susceptibility to NK cell cytotoxicity via Siglec-7 engagement in a
      variety of tumor types. These results support a model in which hypersialylation
      offers a selective advantage to tumor cells under pressure from NK
      immunosurveillance by increasing Siglec ligands. We also exploited this finding
      to protect allogeneic and xenogeneic primary cells from NK-mediated killing,
      suggesting the potential of Siglecs as therapeutic targets in cell transplant
      therapy. 

PMID- 24292069
TI  - Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine.
AB  - Wnts are secreted palmitoylated glycoproteins that are important in embryonic
      development and human cancers. Here we report a method for imaging the
      palmitoylated form of Wnt proteins with subcellular resolution using clickable
      bioorthogonal fatty acids and in situ proximity ligation. Palmitoylated Wnt3a is
      visualized throughout the secretory pathway and trafficks to multivesicular
      bodies that act as export sites in secretory cells. We establish that
      glycosylation is not required for Wnt3a palmitoylation, which is necessary but
      not sufficient for Wnt3a secretion. Wnt3a is palmitoylated by fatty acids 13-16
      carbons in length at Ser209 but not at Cys77, consistent with a slow turnover
      rate. We find that porcupine (PORCN) itself is palmitoylated, demonstrating what
      is to our knowledge the first example of palmitoylation of an MBOAT protein, and
      this modification partially regulates Wnt palmitoylation and signaling. Our data
      reveal the role of O-palmitoylation in Wnt signaling and suggest another layer of
      cellular control over PORCN function and Wnt secretion.

PMID- 24292070
TI  - A conserved water-mediated hydrogen bond network defines bosutinib's kinase
      selectivity.
AB  - Kinase inhibitors are important cancer drugs, but they tend to display limited
      target specificity, and their target profiles are often challenging to
      rationalize in terms of molecular mechanism. Here we report that the clinical
      kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of
      conserved structured water molecules in the active site and that many other
      kinase inhibitors share a similar recognition mechanism. Using the nitrile group
      of bosutinib as an infrared probe, we show that the gatekeeper residue and one
      other position in the ATP-binding site control access of the drug to the
      structured water molecules and that the amino acids found at these positions
      account for the kinome-wide target spectrum of the drug. Our work highlights the
      importance of structured water molecules for inhibitor recognition, reveals a new
      role for the kinase gatekeeper and showcases an effective approach for
      elucidating the molecular origins of selectivity patterns. 

PMID- 24292072
TI  - Wnt acylation: seeing is believing.

PMID- 24292071
TI  - PITPs as targets for selectively interfering with phosphoinositide signaling in
      cells.
AB  - Sec14-like phosphatidylinositol transfer proteins (PITPs) integrate diverse
      territories of intracellular lipid metabolism with stimulated
      phosphatidylinositol-4-phosphate production and are discriminating portals for
      interrogating phosphoinositide signaling. Yet, neither Sec14-like PITPs nor PITPs
      in general have been exploited as targets for chemical inhibition for such
      purposes. Herein, we validate what is to our knowledge the first small-molecule
      inhibitors (SMIs) of the yeast PITP Sec14. These SMIs are nitrophenyl(4-(2
      methoxyphenyl)piperazin-1-yl)methanones (NPPMs) and are effective inhibitors in
      vitro and in vivo. We further establish that Sec14 is the sole essential NPPM
      target in yeast and that NPPMs exhibit exquisite targeting specificities for
      Sec14 (relative to related Sec14-like PITPs), propose a mechanism for how NPPMs
      exert their inhibitory effects and demonstrate that NPPMs exhibit exquisite
      pathway selectivity in inhibiting phosphoinositide signaling in cells. These data
      deliver proof of concept that PITP-directed SMIs offer new and generally
      applicable avenues for intervening with phosphoinositide signaling pathways with
      selectivities superior to those afforded by contemporary lipid kinase-directed
      strategies.

PMID- 24292074
TI  - Bis-cyclooctatetraene tripalladium sandwich complexes.
AB  - We report synthesis and structural characterization of bis-cyclooctatetraene
      trinuclear palladium sandwich complexes. The non-planar cyclooctatetraene ligands
      flank an isosceles Pd3 triangle, which is supported by one equatorial ligand. 

PMID- 24292073
TI  - Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl
      reductase InhA.
AB  - Pyridomycin, a natural product with potent antituberculosis activity, inhibits a
      major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal
      structure and unique ability of pyridomycin to block both the NADH cofactor- and
      lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a
      kind binding mode that discloses a new means of InhA inhibition. Proof-of
      principle studies show how structure-assisted drug design can improve the
      activity of new pyridomycin derivatives. 

PMID- 24292075
TI  - Nanosilver-based antibacterial drugs and devices: mechanisms, methodological
      drawbacks, and guidelines.
AB  - Despite the current advancement in drug discovery and pharmaceutical
      biotechnology, infection diseases induced by bacteria continue to be one of the
      greatest health problems worldwide, afflicting millions of people annually.
      Almost all microorganisms have, in fact, an intrinsic outstanding ability to
      flout many therapeutic interventions, thanks to their fast and easy-to-occur
      evolutionary genetic mechanisms. At the same time, big pharmaceutical companies
      are losing interest in new antibiotics development, shifting their capital
      investments in much more profitable research and development fields. New smart
      solutions are, thus, required to overcome such concerns, and should combine the
      feasibility of industrial production processes with cheapness and effectiveness.
      In this framework, nanotechnology-based solutions, and in particular silver
      nanoparticles (AgNPs), have recently emerged as promising candidates in the
      market as new antibacterial agents. AgNPs display, in fact, enhanced broad-range
      antibacterial/antiviral properties, and their synthesis procedures are quite cost
      effective. However, despite their increasing impact on the market, many relevant
      issues are still open. These include the molecular mechanisms governing the AgNPs
      bacteria interactions, the physico-chemical parameters underlying their toxicity
      to prokaryotes, the lack of standardized methods and materials, and the
      uncertainty in the definition of general strategies to develop smart
      antibacterial drugs and devices based on nanosilver. In this review, we analyze
      the experimental data on the bactericidal effects of AgNPs, discussing the
      complex scenario and presenting the potential drawbacks and limitations in the
      techniques and methods employed. Moreover, after analyzing in depth the main
      mechanisms involved, we provide some general strategies/procedures to perform
      antibacterial tests of AgNPs, and propose some general guidelines for the design
      of antibacterial nanosystems and devices based on silver/nanosilver. 

PMID- 24292076
TI  - Nationwide practice patterns for the use of venous thromboembolism prophylaxis
      among men undergoing radical prostatectomy.
AB  - PURPOSE: To examine the practice patterns and predictors of VTE prophylaxis
      following radical prostatectomy (RP). METHODS: This was a population-based
      observational study of 94,709 men with a diagnosis of prostate cancer (ICD-9 code
      185) who underwent RP were identified from a hospital-based database from 2000 to
      2010, including 68,244 (72.1 %) open RP (ORP) and 26,465 (27.9 %) robotic
      assisted laparoscopic RP (RALP). VTE prophylaxis was classified as none,
      mechanical, pharmacologic, or combination. RESULTS: Following RP, 35,591 (52.2 %)
      received mechanical, 4,945 (7.2 %) pharmacologic, 7,720 (10.6 %) combination, and
      20,438 (30.0 %) no VTE prophylaxis. A total of 245 VTE events (145 DVT, 114 PE)
      were identified, representing 0.25 % of all procedures. Men with >2 comorbidities
      (OR = 2.44; 95 % CI 1.78-3.35) and those who were black (OR = 1.44; 95 % CI 1.06
      1.97) were more likely to have a VTE. Men who had RALP (OR = 0.61; 95 % CI 0.45
      0.99), surgery at high-volume hospitals (OR = 0.45; 95 % CI 0.28-0.73), or
      received prophylaxis (OR = 0.67; 95 % CI 0.50-0.88) were less likely to develop a
      VTE. CONCLUSION: Despite the observation that VTE prophylaxis reduces the risk of
      VTE by 40 %, VTE prophylaxis was not used in almost one-third of men who
      underwent radical prostatectomy.

PMID- 24292077
TI  - Robot-assisted rectopexy and colpopexy for rectal prolapse.
AB  - AIM: This video demonstrates a technique for robot-assisted combined rectopexy
      with colpopexy, but without the use of mesh for rectal prolapse. METHODS: This
      case features a 61-year-old woman who presents with complaints of tissue
      protruding through her rectum and fecal incontinence. On examination, she was
      found to have circumferential, full-thickness rectal prolapse and perineal
      descent. We present a technique that combines rectopexy with colpopexy without
      the use of mesh for repair of rectal prolapse. Postoperative examination revealed
      resolution of rectal prolapse and good perineal support. This video illustrates a
      technique that may serve as a useful adjunct to have in one's surgical
      armamentarium in circumstances when mesh should not or cannot be used, such as in
      cases that require resection of the sigmoid colon or for patients who simply
      prefer to avoid the use of mesh. CONCLUSION: Given that rectal prolapse and
      posthysterecomy vaginal vault prolapse often occur together, our institution
      routinely performs colpopexy with rectopexy for rectal prolapse to provide
      additional support to the pelvic floor as demonstrated in this video.

PMID- 24292078
TI  - Changes in the outcomes of severe trauma patients from 15-year experience in a
      Western European trauma ICU of Emilia Romagna region (1996-2010). A population
      cross-sectional survey study.
AB  - BACKGROUND: Our experience in trauma center management increased over time and
      improved with development of better logistics, optimization of structural and
      technical resources. In addition recent Government policy in safety regulations
      for road traffic accident (RTA) prevention, such compulsory helmet use (2000) and
      seatbelt restraint (2003) were issued with aim of decreasing mortality rate for
      trauma. INTRODUCTION: The evaluation of their influence on mortality during the
      last 15 years can lead to further improvements. METHODS: In our level I trauma
      center, 60,247 trauma admissions have been recorded between 1996 and 2010, with
      2183 deaths (overall mortality 3.6 %). A total of 2,935 trauma patients with ISS
      >16 have been admitted to Trauma ICU and recorded in a prospectively collected
      database (1996-2010). Blunt trauma occurred in 97.1 % of the cases, whilst only
      2.5 % were penetrating. A retrospective review of the outcomes was carried out,
      including mortality, cause of death, morbidity and length of stay (LOS) in the
      intensive care unit (ICU), with stratification of the outcome changes through the
      years. Age, sex, mechanism, glasgow coma scale (GCS), systolic blood pressure
      (SBP), respiratory rate (RR), revised trauma score (RTS), injury severity score
      (ISS), pH, base excess (BE), as well as therapeutic interventions (i.e.,
      angioembolization and number of blood units transfused in the first 24 h), were
      included in univariate and multivariate analyses by logistic regression of
      mortality predictive value. RESULTS: Overall mortality through the whole period
      was 17.2 %, and major respiratory morbidity in the ICU was 23.3 %. A significant
      increase of trauma admissions has been observed (before and after 2001, p <
      0.01). Mean GCS (10.2) increased during the period (test trend p < 0.05). Mean
      age, ISS (24.83) and mechanism did not change significantly, whereas mortality
      rate decreased showing two marked drops, from 25.8 % in 1996, to 18.3 % in 2000
      and again down to 10.3 % in 2004 (test trend p < 0.01). Traumatic brain injury
      (TBI) accounted for 58.4 % of the causes of death; hemorrhagic shock was the
      death cause in 28.4 % and multiple organ failure (MOF)/sepsis in 13.2 % of the
      patients. However, the distribution of causes of death changed during the period
      showing a reduction of TBI-related and increase of MOF/sepsis (CTR test trend p <
      0.05). Significant predictors of mortality in the whole group were year of
      admission (p < 0.05), age, hemorrhagic shock and SBP at admission, ISS and GCS,
      pH and BE (all p < 0.01). In the subgroup of patients that underwent emergency
      surgery, the same factors confirmed their prognostic value and remained
      significant as well as the adjunctive parameter of total amount of blood units
      transfused (p < 0.05). Surgical time (mean 71 min) showed a significant trend
      towards reduction but did not show significant association with mortality (p =
      0.06). CONCLUSION: Mortality of severe trauma decreased significantly during the
      last 15 years as well as mean GCS improved whereas mean ISS remained stable. The
      new safety regulations positively influenced incidence and severity of TBI and
      seemed to improve the outcomes. ISS seems to be a better predictor of outcome
      than RTS.

PMID- 24292079
TI  - Bioengineering radioresistance by overproduction of RPA, a mammalian-type single
      stranded DNA-binding protein, in a halophilic archaeon.
AB  - Halobacterium sp. NRC-1 is a wild-type extremophilic microbe that is naturally
      tolerant to high levels of ionizing radiation. Mutants of strain NRC-1 with even
      higher levels of resistance to ionizing radiation, named RAD, were previously
      isolated after selecting survival to extremely high doses of ionizing radiation.
      These RAD mutants displayed higher transcription levels for the rfa3 operon,
      coding two subunits of the RPA-like putative single-stranded binding protein,
      rfa3 and rfa8, and a third downstream gene, ral. In order to bioengineer cells
      with increased tolerance to ionizing radiation and further explore the genetic
      basis of the RAD phenotype, we placed the rfa3 operon under control of the gvpA
      promoter in a Halobacterium expression plasmid, pDRK1. When pDRK1 was introduced
      into the wild-type NRC-1 strain, overproduction of the Rfa3 and Rfa8 proteins was
      observed by Western blotting and proteomic analysis. The Halobacterium strains
      expressing Rfa3 and Rfa8 also displayed improved survival after exposure to
      ionizing radiation, similar to the RAD mutants, when compared to wild-type strain
      NRC-1. The Rfa3 and Rfa8 proteins co-purified by affinity chromatography on
      single-stranded DNA cellulose columns, confirming the ability of the proteins to
      bind to single-stranded DNA as well as their relative abundance in the wild-type,
      RAD mutants, and rfa3 operon overexpression strains. These results clearly
      establish that overexpression of haloarchaeal RPA promotes ionizing radiation
      resistance in Halobacterium sp. NRC-1 and that the Rfa3 and Rfa8 subunits bind
      single-stranded DNA. Bioengineering cells with increased levels of ionizing
      radiation resistance may have potential value in medical and environmental
      applications. 

PMID- 24292080
TI  - Allantoin catabolism influences the production of antibiotics in Streptomyces
      coelicolor.
AB  - Purines are a primary source of carbon and nitrogen in soil; however, their
      metabolism is poorly understood in Streptomyces. Using a combination of
      proteomics, metabolomics, and metabolic engineering, we characterized the
      allantoin pathway in Streptomyces coelicolor. When cells grew in glucose minimal
      medium with allantoin as the sole nitrogen source, quantitative proteomics
      identified 38 enzymes upregulated and 28 downregulated. This allowed identifying
      six new functional enzymes involved in allantoin metabolism in S. coelicolor.
      From those, using a combination of biochemical and genetic engineering tools, it
      was found that allantoinase (EC 3.5.2.5) and allantoicase (EC 3.5.3.4) are
      essential for allantoin metabolism in S. coelicolor. Metabolomics showed that
      under these growth conditions, there is a significant intracellular accumulation
      of urea and amino acids, which eventually results in urea and ammonium release
      into the culture medium. Antibiotic production of a urease mutant strain showed
      that the catabolism of allantoin, and the subsequent release of ammonium,
      inhibits antibiotic production. These observations link the antibiotic production
      impairment with an imbalance in nitrogen metabolism and provide the first
      evidence of an interaction between purine metabolism and antibiotic biosynthesis.

PMID- 24292082
TI  - Identification of novel GAPDH-derived antimicrobial peptides secreted by
      Saccharomyces cerevisiae and involved in wine microbial interactions.
AB  - Saccharomyces cerevisiae plays a primordial role in alcoholic fermentation and
      has a vast worldwide application in the production of fuel-ethanol, food and
      beverages. The dominance of S. cerevisiae over other microbial species during
      alcoholic fermentations has been traditionally ascribed to its higher ethanol
      tolerance. However, recent studies suggested that other phenomena, such as
      microbial interactions mediated by killer-like toxins, might play an important
      role. Here we show that S. cerevisiae secretes antimicrobial peptides (AMPs)
      during alcoholic fermentation that are active against a wide variety of wine
      related yeasts (e.g. Dekkera bruxellensis) and bacteria (e.g. Oenococcus oeni).
      Mass spectrometry analyses revealed that these AMPs correspond to fragments of
      the S. cerevisiae glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein. The
      involvement of GAPDH-derived peptides in wine microbial interactions was further
      sustained by results obtained in mixed cultures performed with S. cerevisiae
      single mutants deleted in each of the GAPDH codifying genes (TDH1-3) and also
      with a S. cerevisiae mutant deleted in the YCA1 gene, which codifies the
      apoptosis-involved enzyme metacaspase. These findings are discussed in the
      context of wine microbial interactions, biopreservation potential and the role of
      GAPDH in the defence system of S. cerevisiae. 

PMID- 24292081
TI  - Influence of transitional states on the microbial ecology of anaerobic digesters
      treating solid wastes.
AB  - A better understanding of the microbial ecology of anaerobic processes during
      transitional states is important to achieve a long-term efficient reactor
      operation. Five wastes (pig manure, biodiesel residues, ethanol stillage,
      molasses residues, and fish canning waste) were treated in five anaerobic
      reactors under the same operational conditions. The influence of the type of
      substrate and the effect of modifying feeding composition on the microbial
      community structure was evaluated. The highest biomethanation efficiency was
      observed in reactors fed with fish canning waste, which also presented the
      highest active archaeal population and the most diverse microbial communities.
      Only two Bacteria populations could be directly related to a particular
      substrate: Ilyobacter with biodiesel residues and Trichococcus with molasses
      residues. Results showed that the time to achieve steady-state performance after
      these transitional states was not dependent on the substrate treated. But
      reactors needed more time to handle the stress conditions derived from the start
      up compared to the adaptation to a new feeding. Cluster analyses showed that the
      type of substrate had a clear influence on the microbiology of the reactors, and
      that segregation was related to the reactors performance. Finally, we conclude
      that the previous inoculum history treating solid waste and higher values of
      active Archaea population are important factors to face a successful change in
      substrate not entailing stability failure. 

PMID- 24292083
TI  - Varicella-zoster virus vaccine, successes and difficulties.
AB  - Despite intensive efforts in recent decades to develop preventive or therapeutic
      vaccines against diseases caused by herpes simplex virus (HSV), or varicella
      zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes
      viruses,a safe and efficient vaccine has been approved for commercial development
      only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It
      consists of amixture of at least 13 subpopulations of viruses, all with
      deletions, insertions or mutations in the genome; the most common mutations are
      observed in the open reading frame 62 (ORF62). Experience over more than 30 years
      in Japan, the USA and other countries where VZV vaccination is provided has
      demonstrated that the vaccine is safe and the effectiveness of two doses compared
      to unvaccinated children is 98-99%. When administered in a higher dose to
      stimulate the declining cell-mediated immunity, the same vaccine has been shown
      to reduce the incidence and severity of herpes zoster in immunocompetent
      individuals older than 60 years. Vaccination of immuno-compromised subjects with
      this VZV vaccine is problematic and various strategies need to be explored.
      Differences in the pathomechanisms of infection, latency and immune evasion of
      VZV and HSV, together with host genetic factors, may explain the availability of
      the successful VZV vaccine and the failures of the past HSV vaccine candidates. 

PMID- 24292084
TI  - Evolutionary epidemiology of Neisseria meningitidis strains in Belarus compared
      to other European countries.
AB  - INTRODUCTION: Meningococcal infections are major causes of death in children
      globally. In Belarus, the incidence of cases and fatality rate of meningococcal
      infections are low and comparable to the levels in other European countries. AIM:
      In the present study, the molecular and epidemiological traits of Neisseria
      meningitidis strains circulating in Belarus were characterized and compared to
      isolates from other European countries. MATERIALS AND METHODS: Twenty N.
      meningitidis strains isolated from patients (n = 13) and healthy contacts (n = 7)
      during 2006-2012 in Belarus were selected for multilocus sequence typing (MLST),
      genosubtyping and FetA typing. TheSTs of the Belarusian strains were
      phylogenetically compared to the STs of 110 selected strains from 22 other
      European countries. RESULTS: Overall, eleven different genosubtypes were
      observed, there were seven variants of variable region of the fet Agene detected.
      The majority of the STs (95%) found in Belarus were novel and allthose were
      submitted to the Neisseria MLST database for assignment. Several newly discovered
      alleles of fumC (allele 451) and gdh (allele 560 and 621) appeared to be
      descendants of alleles which are widespread in Europe, and single aroE alleles
      (602 and 603) occurred as a result of separate evolution. CONCLUSIONS: N.
      meningitidis strains circulating in Belarus are heterogeneous and include
      sequence types, possibly, locally evolved in Belarus as well as representatives
      of widespread European hyperinvasive clonal complexes.

PMID- 24292085
TI  - Bacteriophage therapy against staphylococci.
AB  - The emergence of the multi-drug-resistant Staphylococcus aureus strains has
      prompted interest in alternatives to conventional drugs. Among the possible
      options one of the most promising is the therapeutic use of bacteriophages. Over
      the recent decades, increasing amount of literature has validated the use of
      bacteriophages for therapy and prophylaxis against drug-resistant staphylococci.
      This work attempts to review the current knowledge on bacteriophages and their
      usages for treatment of staphylococcal diseases. 

PMID- 24292086
TI  - Changes in the hormone (ACTH, insulin,epinephrine) content of immune cells in
      children having acute lymphocytic leukemia (ALL).
AB  - Immune cells synthesize, store and secrete hormones, the level of which changes
      in ALL. In previous experiments the level of histamine, serotonin and
      triiodothyronine (T3)was studied, while at present that of ACTH, insulin and
      epinephrine, using flow cytometric analysis for the determination of cell subsets
      and detection of hormone content. The measurements were done in children at the
      time of diagnosis. ACTH was significantly elevated in each T cell subsets (total
      T, Th, Tc, activated T), while B and NK cells were not touched. The alterations
      in the insulin content (decrease in Tc and activated T cells) were uncertain, and
      NK cells contained significantly less insulin. The disease did not influence the
      cells' epinephrine content. There is not clear explanation for the importance of
      changes in the cells' hormone content, however, it is discussed in the text.

PMID- 24292087
TI  - Molecular characterization of vancomycin-resistant enterococci in Serbia:
      intensive care unit as the source.
AB  - The purpose of this study was to evaluate the molecular relatedness of clinical
      isolates of vancomycin-resistant enterococci (VRE) collected from patients of the
      Clinic for Infectious and Tropical Diseases in Belgrade. Among 40 isolates
      available for the investigation, 36 were identified as Enterococcus faecium,
      whereas 2 were Enterococcus faecalis and Enterococcus raffinosus, respectively.
      Pulsed-field gel electrophoresis (PFGE) typing revealed 21 strain types,
      comprising 7 clusters which contained at least two isolates and 14 unique PFGE
      patterns. Although we searched for pathogenicity factor genes (gelE, cylB, asa1,
      efaAfs, esp, cpd, cob) in representatives of all macro-restriction patterns, they
      have been confirmed in only one clone of E. faecalis. Genes esp and hyl, commonly
      found in E. faecium, were yilded in 10 macro-restriction patterns of this
      species, and their presence could not be ascribed to clonally related strains (p
      = 0.05). All VRE isolates were multiresistant and positive for vanA gene. Twenty
      strains of VRE and 6 clusters obtained from Intensive care unit (ICU) are proof
      of intensive transmission of these microorganisms at this department. The results
      of this study suggest wide genotypic variability among the clinical VRE isolates,
      but also intrahospital dissemination of some of them. 

PMID- 24292088
TI  - Immunochemistry of adenoviruses: limitations and new horizons of gene therapy.
AB  - Adenoviruses have increasingly been recognized as significant viral pathogens
      causing high morbidity and mortality especially among immunocompromised
      individuals such as transplant recipients and AIDS patients. Through the
      infection process, after the adenovirus fiber and penton are bonded to cell
      surface receptors through special amino acid moieties, secondary messengers
      activate protein kinases, pro-inflammatory cytokines and chemokines. Serotype and
      species specific antibodies also are induced. Recombinant human adenoviruses have
      been pivotal in the development of gene therapy strategies and have shown a great
      promise for the treatment of genetic disorders and malignancies. Recent studies
      have enlightened their harmful immunological effects dependent on fiber and hexon
      polypeptide structure and receptor binding. Pre-existing antibodies or those
      elicited by vectors neutralize input recombinant adenovirus particles rendering
      them ineffective. Mediators induce serious even lethal side effects and cytotoxic
      reactions which extinguish transgene expression. To overcome these difficulties
      new strategies are required in the application of recombinant adenoviruses to
      redirect vector entry from the natural receptors to alternative binding sites or
      using rare human or animal adenovirus fiber molecules to modify the native fiber
      structure by altering amino acid structure and creating chimeric fibers. This
      requires searching for, isolating and characterizing new serotypes, mutants or
      variants for new generation vectors. Human adenovirus 1 feline isolate (feline
      adenovirus) might fulfil these criteria.

PMID- 24292089
TI  - In vitro efficiency of vancomycin containing experimental drug delivery systems.
AB  - Biofilm-forming Staphylococcus epidermidis strains are common cause of the
      periprosthetic infection. The treatment of the periprosthetic infection is very
      problematic, so the prevention of these infections by an antibiotic containing
      prothesis could be an option for prevention.The purpose of the present study was
      to examine the in vitro effects of drug delivery systems (DDSs), namely Wax 1 and
      Wax 2 with different vancomycin content: 0.5, 1, 2 and 4 mg. In order to control
      the antibacterial activity of DDSs killing curve study was performed and in order
      to determine the antibiotic release and the antibiotic peak concentration from
      the DDSs biological assay was carried out.The time kill curve studies showed,
      that both DDSs with all vancomycin concentration decreased significantly the
      bacterial counts, however, Wax 2 with 4 mg vancomycin significantly decreased the
      bacterial count than all the other groups.The vancomycin release was the best
      with the highest peak concentration from DDSs with 4 mg vancomycin contain; it
      was significantly better than in the other groups, however, no significant
      difference was observed between Wax 1 and Wax 2 in this respect.These findings
      suggest that Wax 2 with 4 mg vancomycin content could be a potential agent for
      clinical use. 

PMID- 24292090
TI  - Proteomic analysis of the proteins that are associated with the resistance to
      paclitaxel in human breast cancer cells.
AB  - Cancers frequently develop resistance to paclitaxel but the underlying molecular
      mechanisms remain to be determined. We have investigated the proteins that are
      associated with the paclitaxel resistance in human breast cancer MCF-7 cells
      using proteomic analysis. Paclitaxel resistant human breast cancer MCF-7 cells
      (MCF-7/P) were established by escalating the concentrations of paclitaxel to drug
      sensitive MCF-7 cells (MCF-7/S). The global protein profiles of MCF-7/P and MCF
      7/S were compared using two-dimensional gel electrophoresis (2-DE) and matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS). Eleven proteins were upregulated while six proteins were downregulated in
      MCF-7/P cells. Western blot and real-time PCR analyses showed that the protein
      and mRNA levels of heterogeneous nuclear ribonucleoprotein (hnRNP C1/C2), SET
      nuclear oncogene (SET), aspartate aminotransferase (AAT), transgelin-2 (TAGLN2)
      were increased, while those of nucleoside-diphosphate kinase A (NDKA) were
      decreased in MCF-7/P cells. Accordingly, knockdown of TAGLN2 by siRNA sensitized
      MCF-7/P cells to paclitaxel and reduced the multidrug resistance (MDR). Our
      identification of differential proteins, particularly transgelin-2, provides new
      insights into the mechanism of MDR to paclitaxel and novel biological targets for
      breast cancer treatment. 

PMID- 24292092
TI  - Expression of Foxp3 and interleukin-17 in lichen planus lesions with emphasis on
      difference in oral and cutaneous variants.
AB  - Foxp3 is a specific marker for regulatory T cells (Tregs), and interleukin (IL)
      17 is the signature cytokine of T-helper (Th) 17 cells. Recent studies suggested
      that Foxp3+ Tregs and IL-17+ Th17 cells may be involved in pathogenesis of lichen
      planus (LP). The objectives of this study were to examine the immunoexpression of
      Foxp3 and IL-17 in archival paraffin-embedded biopsy specimens from 80 cases of
      LP (oral LP, n = 42; cutaneous LP, n = 38) and compare against normal control
      tissues (oral mucosa, n = 10; skin, n = 10). The results showed that the mean
      number of Foxp3 and IL-17 expression in LP was significantly higher compared to
      controls, respectively (both P < 0.001). A positive correlation between Foxp3 and
      IL-17 expression (r = 0.273; P = 0.014) was observed. Moreover, the mean number
      of Foxp3 expression in oral LP was significantly higher than cutaneous LP (P <
      0.001). Collectively, our findings demonstrated the increased expression of Foxp3
      and IL-17 in LP lesions including oral and cutaneous variants. Foxp3 expressing
      in oral LP was higher than cutaneous LP, which may be associated with the
      difference in clinical behaviour of the two variants of the disease. Further
      studies are required to investigate the immunopathologic mechanisms and
      therapeutic target of Foxp3+ Tregs and IL-17+ Th17 cells in LP. 

PMID- 24292093
TI  - Fli1 deficiency contributes to the suppression of endothelial CXCL5 expression in
      systemic sclerosis.
AB  - CXCL5 is a member of CXC chemokines with neutrophilic chemoattractant and pro
      angiogenic properties, which has been implicated in the pathological angiogenesis
      of rheumatoid arthritis and inflammatory bowel diseases. Since aberrant
      angiogenesis is also involved in the developmental process of systemic sclerosis
      (SSc), we herein measured serum CXCL5 levels in 63 SSc and 18 healthy subjects
      and investigated their clinical significance and the mechanism explaining altered
      expression of CXCL5 in SSc. Serum CXCL5 levels were significantly lower in SSc
      patients than in healthy subjects. In diffuse cutaneous SSc (dcSSc), serum CXCL5
      levels were uniformly decreased in early stage (<1 year) and positively
      correlated with disease duration in patients with disease duration of <6 years.
      In non-early stage dcSSc (>=1 year), decreased serum CXCL5 levels were linked to
      the development of digital ulcers. Consistently, the expression levels of CXCL5
      proteins were decreased in dermal blood vessels of early stage dcSSc.
      Importantly, Fli1 bound to the CXCL5 promoter and its gene silencing
      significantly suppressed the CXCL5 mRNA expression in human dermal microvascular
      endothelial cells. Furthermore, endothelial cell-specific Fli1 knockout mice, an
      animal model of SSc vasculopathy, exhibited decreased CXCL5 expression in dermal
      blood vessels. Collectively, these results indicate that CXCL5 is a member of
      angiogenesis-related genes, whose expression is suppressed at least partially due
      to Fli1 deficiency in SSc endothelial cells. Since Fli1 deficiency is deeply
      related to aberrant angiogenesis in SSc, it is plausible that serum CXCL5 levels
      inversely reflect the severity of SSc vasculopathy. 

PMID- 24292094
TI  - Non-affine fields in solid-solid transformations: the structure and stability of
      a product droplet.
AB  - We describe the microstructure, morphology, and dynamics of growth of a droplet
      of martensite nucleating in a parent austenite during a solid-solid
      transformation, using a Landau theory written in terms of both conventional
      affine elastic deformations and non-affine deformations. Non-affineness, phi,
      serves as a source of strain incompatibility and screens long-ranged elastic
      interactions. It is produced wherever the local stress exceeds a threshold and
      anneals diffusively thereafter. Using a variational calculation, we find three
      types of stable solution (labeled I, II, and III) for the structure of the
      product droplet, depending on the stress threshold and the scaled mobilities of
      phi parallel and perpendicular to the parent-product interface. The profile of
      the non-affine field phi is different in these three solutions: I is
      characterized by a vanishingly small phi, II admits large values of phi localized
      in regions of high stress within the parent-product interface, and III is a
      structure in which phi completely wets the parent-product interface. The width l
      and size W of the twins follow the relation l is proportional to ?W in solution
      I; this relation does not hold for II or III. We obtain a dynamical phase diagram
      featuring these solutions, and argue that they represent specific solid-state
      microstructures.

PMID- 24292095
TI  - The persistence of symptom burden: symptom experience and quality of life of
      cancer patients across one year.
AB  - PURPOSE: The purpose of this longitudinal study was to track the symptom
      experience in a sample of cancer patients, determine the persistence of cancer
      symptoms and symptom burden, and examine the relationship between symptoms and
      QOL over time. METHODS: Five hundred forty-two patients provided longitudinal
      data, completing surveys over a 12-month period. Patients had breast, colorectal,
      gynecologic, lung, or prostate cancer with stage 1, 2, or 3 disease. Surveys
      included the Memorial Symptom Assessment Scale and the Functional Assessment of
      Cancer Therapy-General Scale and were administered every 3 months. Demographic
      and clinical information and comorbidities were collected from the tumor
      registry. RESULTS: The number and type of symptoms experienced by patients varied
      by cancer type, but about 90% of patients reported one or more symptoms--with
      prostate cancer patients reporting fewer symptoms and colorectal patients, more
      symptoms. Prostate patients also had the lowest symptom burden at every time
      point. Overall, symptom burden decreased over time, as did the Physical subscale
      for the MSAS. Quality of life was stable over time, except for physical well
      being, which improved. Quality of life was negatively correlated with symptom
      burden at every time point. CONCLUSIONS: The differences in symptom experience by
      cancer type suggest that assessment and management of symptoms must be
      individually tailored or at least adjusted by cancer type. While symptom burden
      decreased over time, residual symptom burden was still noteworthy. As quality of
      life was persistently negatively correlated with symptom burden, the results
      suggest the need for comprehensive symptom assessment and management.

PMID- 24292096
TI  - Reduction of health risk factors through an adapted physical activity program in
      patients with breast cancer.
AB  - PURPOSE: After a breast cancer diagnosis, patients are at high risk of reducing
      their physical activity and gaining weight. Lack of physical activity and weight
      gain are known negative but modifiable prognostic factors. An observational study
      of a 3-month adapted physical activity (APA) program was performed to assess its
      effectiveness in improving physical activity level and reducing risk factors
      related to health during or after breast cancer treatments. METHOD: Height,
      weight, and waist circumference (WC) were measured at the beginning and end of
      the 26-session program. Body mass index (BMI) and WC to height ratio (WHtR) were
      calculated. Physical activity profile, aerobic capacity, and usual average daily
      energy expenditure were estimated. Median values were compared using
      nonparametric tests. RESULTS: Sixty-one (61) voluntary breast cancer patients
      attended 80% of the sessions. At baseline, median (minimum-maximum) BMI was 23.3
      (16.1-36.8) kg.m(-2) and WC and WHtR showed metabolic risks. After 3 months,
      anthropometric data remained stable. Moderate physical activity significantly
      improved (+13 min/day) and sedentary tended to decrease (-18 min/day).
      CONCLUSION: A 3-month APA program allows patients to limit risk factors related
      to health such as physical inactivity and metabolic risks. This study reinforces
      the need to promote physical activity as early as possible in cancer patients'
      care.

PMID- 24292097
TI  - Fe2O3 nanoparticles wrapped in multi-walled carbon nanotubes with enhanced
      lithium storage capability.
AB  - We have designed a novel hybrid nanostructure by coating Fe2O3 nanoparticles with
      multi-walled carbon nanotubes to enhance the lithium storage capability of Fe2O3.
      The strategy to prepare Fe2O3@MWCNTs involves the synthesis of Fe nanoparticles
      wrapped in MWCNTs, followed by the oxidation of Fe nanoparticles under carbon
      dioxide. When used as the anode in a Li-ion battery, this hybrid material (70.32
      wt% carbon nanotubes, 29.68 wt% Fe2O3) showed a reversible discharge capacity of
      515 mAhg-1 after 50 cycles at a density of 100 mAg-1 and the capacity based on
      Fe2O3 nanoparticles was calculated as 1147 mAhg-1, Three factors are responsible
      for the superior performance: (1) The hollow interiors of MWCNTs provide enough
      spaces for the accommodation of large volume expansion of inner Fe2O3
      nanoparticles, which can improving the stability of electrode; (2) The MWCNTs
      increase the overall conductivity of the anode; (3) A stable solid electrolyte
      interface film formed on the surface of MWCNTs may reduce capacity fading.

PMID- 24292098
TI  - Time since last vaccine dose in PCR-positive and PCR-negative children with
      suspected pertussis to monitor pertussis vaccine effectiveness.
AB  - We evaluated whether the results of diagnostic polymerase chain reaction (PCR)
      testing combined with time since last vaccine dose could be used to monitor the
      effectiveness of acellular pertussis vaccines. In 258 consecutive nasopharyngeal
      swabs from children and adolescents with typical pertussis symptoms, 80 were
      positive and 178 were negative in PCR for Bordetella pertussis DNA (IS 481). Time
      since last vaccine dose was available for 152 patients, of which 120 were fully
      immunised. Among the fully vaccinated patients, the median age of 41 PCR-positive
      patients was 8.4 years (range 0.9-12.3) and that of 79 PCR-negative cases was 3.3
      years (range 0.4-14.1) (p < 0.01). The median time since last pertussis vaccine
      dose was 6.05 years [95 % confidence interval (CI): 0.5-10.9] in PCR-positive
      cases and 2.22 years (95 % CI: 0.04-9.23) in PCR-negative cases (p < 0.001). The
      use of diagnostic PCR results from pertussis cases together with time since last
      vaccine dose permits estimates of the duration of protection after vaccination
      with acellular pertussis vaccines that are in keeping with more complex studies.

PMID- 24292099
TI  - Combination therapy with iron chelation and vancomycin in treating murine
      staphylococcemia.
AB  - Iron acquisition is a virulence factor for Staphylococcus aureus. We assessed the
      efficacy of the iron chelator, deferasirox (Def), alone or in combination with
      vancomycin (Van) against two methicillin-resistant S. aureus (MRSA) strains in
      vitro and in a murine bacteremia model. In vitro time-kill assays were carried
      out against MRSA or vancomycin-intermediate S. aureus (VISA) strains. The impact
      of Def on Van binding to the surface of S. aureus was measured by flow cytometry.
      Furthermore, we compared the efficacy of Def, Van, or both drugs in treating S.
      aureus bacteremia in a murine model. Combination therapy reduced MRSA and VISA
      viability in vitro versus either drug alone or untreated controls (p < 0.005);
      this outcome was correlated with enhanced Van surface binding to S. aureus cells.
      In vivo, Def + Van combination therapy significantly reduced the bacterial burden
      in mice kidneys (p = 0.005) and spleen (p < 0.001), and reduced the severity of
      infection with MRSA or VISA strains compared to placebo-treated mice. Our results
      show that Def enhances the in vitro and in vivo capacity of Van-mediated MRSA
      killing via a mechanism that appears to involve increased binding of Van to the
      staphylococcal surface. Iron chelation is a promising, novel adjunctive
      therapeutic strategy for MRSA and VISA infections.

PMID- 24292100
TI  - P-fimbriae in the presence of anti-PapA antibodies: new insight of antibodies
      action against pathogens.
AB  - Uropathogenic strains of Escherichia coli establish urinary tract infections by
      attaching to host epithelial cells using adhesive organelles called fimbriae.
      Fimbriae are helix-like structures with a remarkable adaptability, offering
      safeguarding for bacteria exposed to changing fluid forces in the urinary tract.
      We challenged this property of P-fimbriae by cross-linking their subunits with
      shaft-specific antibodies and measuring the corresponding force response at a
      single organelle level. Our data show compromised extension and rewinding of P
      fimbriae in the presence of antibodies and reduced fimbrial elasticity, which are
      important properties of fimbriae contributing to the ability of bacteria to cause
      urinary tract infections. The reduced elasticity found by cross-linking fimbrial
      subunits could thus be another assignment for antibodies; in addition to marking
      bacteria as foreign, antibodies physically compromise fimbrial function. We
      suggest that our assay and results will be a starting point for further
      investigations aimed at inhibiting sustained bacterial adhesion by antibodies. 

PMID- 24292101
TI  - BP5 regulated B cell development promoting anti-oxidant defence.
AB  - Bursa of Fabricius is the humoral immune system for B cell differentiation and
      antibody production. Bursopentine (BP5) is a novel immunomodulatory peptide and
      significantly stimulated an antigen-specific immune response in mice. BP5 was
      also found to protect LPS-activated murine peritoneal macrophages from oxidative
      stress. In this study, the effects of BP5 on B cell development were examined.
      The results suggested that BP5 markedly promoted B cell development by increasing
      CFU-pre B, and affected the redox homeostasis regulation of B cells. To study the
      molecular mechanism of effect of bursal-derived BP5, this research utilized 2D-E
      and MALDI-TOF/TOF to analyze the differentially expressed proteins of BP5-treated
      WEHI-231 cells. The results showed that BP5 affected the redox homeostasis
      regulation of WEHI-231 cells and induced alterations in the protein expression
      profiles related to the oxidoreduction coenzyme metabolic process, precursor
      metabolites and energy, proteolysis, RNA splicing and translation and cellular
      process, respectively. BP5 also induced glucose-6-phosphate dehydrogenase (G6PD)
      activity, an essential anti-oxidant cofactor. We found that the redox homeostasis
      regulation effect of BP5 was reduced in G6PD-deficient cells. These data
      suggested that BP5 affected the redox balance toward reducing conditions by
      promoting the expression of G6PD, which in turn regulated the glutathione redox
      cycle and other processes.

PMID- 24292102
TI  - Changes of several brain receptor complexes in the cerebral cortex of patients
      with Alzheimer disease: probable new potential pharmaceutical targets.
AB  - Although Alzheimer disease (AD) has been linked to defects in major brain
      receptors, studies thus far have been limited to the determination of receptor
      subunits or specific ligand binding studies. However, the availability of current
      technology enables the determination and quantification of brain receptor
      complexes. Thus, we examined levels of native receptor complexes in the brains of
      patients with AD. Cortical tissue was obtained from control subjects (n = 12
      females and 12 males) and patients with AD (n = 12 females and 12 males) within a
      3-h postmortem time period. The tissues were kept frozen until further
      biochemical analyses. Membrane proteins were extracted and subsequently enriched
      by ultracentrifugation using a sucrose gradient. Membrane proteins were then
      electrophoresed onto native gels and immunoblotted using antibodies against
      individual brain receptors. We found that the levels were comparable for
      complexes containing GluR2, GluR3 and GluR4 as well as 5-HT1A. Moreover, the
      levels of complexes containing muscarinic AChR M1, NR1 and GluR1 were
      significantly increased in male patients with AD. Nicotinic AChRs 4 and 7 as well
      as dopaminergic receptors D1 and D2 were also increased in males and females with
      AD. These findings reveal a pattern of altered receptor complex levels that may
      contribute to the deterioration of the concerted activity of these receptors and
      thus result in cognitive deficits observed in patients with AD. It should be
      emphasised that receptor complexes function as working units rather than
      individual subunits. Thus, the receptor deficits identified may be relevant for
      the design of experimental therapies. Therefore, specific pharmacological
      modulation of these receptors is within the pharmaceutical repertoire.

PMID- 24292104
TI  - H2O2 activation with biomimetic non-haem iron complexes and AcOH: connecting the
      g = 2.7 EPR signal with a visible chromophore.
AB  - Mechanistic studies of H2O2 activation by complexes related to
      [(BPMEN)Fe(II)(CH3CN)2](2+) with electron-rich pyridines revealed that a new
      intermediate formed in the presence of acetic acid with a 465 nm visible band can
      be associated with an unusual g = 2.7 EPR signal. We postulate that this
      chromophore is an acylperoxoiron(III) intermediate.

PMID- 24292105
TI  - Epidemiological analysis of hereditary endometrial cancer in a large study
      population.
AB  - AIMS: To determine the prevalence of hereditary endometrial cancer and the
      clinical and molecular characteristics of hereditary endometrial cancer patients.
      METHODS: Standardized oncological family histories were collected from 704
      consecutive patients with endometrial cancer from January 2006 to April 2012 and
      analyzed using internationally approved and modified diagnostic criteria based on
      the Amsterdam I and II criteria. Blood samples were collected from 648 patients.
      Paraffin embedded tissues for immunohistochemical examination were gathered from
      109 patients. All patients were split into two main groups corresponding to
      hereditary and sporadic endometrial cancer. RESULTS: The prevalence of hereditary
      endometrial cancer was established as 2.7 % (95 % CI 1.7-4.2 %) or 19/704
      patients. 15/19 (78.9 %; 95 % CI 56.7-91.5 %) patients were diagnosed in stage I.
      Grade 2 tumors were the most common ones with 11/19 (57.9 %; 95 % CI 36.3-76.9 %)
      patients. In the MLH1 gene, two patients were carrying the missense mutations
      P640S (rs63749792) and I219V (rs1799977) each. In the MSH2 gene, one had the
      splice site mutation IV5+3A>T while another had the missense mutation G322D
      (rs4987188). In the MSH6 gene, two were carrying the frameshift mutations
      2150TCAG (rs63750159) and 1050delC each. No clinically putative significant
      mutations were found in two patients. CONCLUSIONS: No significant survival, stage
      and grade of differentiation differences were observed between the hereditary
      group and the sporadic group. Clinical and molecular investigations promote an
      earlier diagnosis of endometrial cancer in families where at least three first
      degree relatives have endometrial cancer.

PMID- 24292106
TI  - Do uterotonic drugs increase risk of abruptio placentae and eclampsia?
AB  - PURPOSE: To determine whether the use of uterotonics, including oxytocin and
      prostaglandins, increases the risk of abruptio placentae and eclampsia. MATERIALS
      AND METHODS: A retrospective analysis was conducted among 260,174 Japanese women
      at term. Demographic characteristics were studied as possible candidates for risk
      factors of abruptio placentae and eclampsia using multivariate logistic
      regression analyses. RESULTS: A total of 1,058 (0.41 %) and 147 (0.06 %) women
      developed abruptio placentae and eclampsia, respectively. Abruptio placentae and
      eclampsia occurred in 177 (0.29 %) and 42 (0.07 %) of the 61,857 women treated
      with uterotonics, respectively. Multivariate regression analyses indicated that
      uterotonics did not increase risk of developing either abruptio placentae or
      eclampsia. Primiparity [odds ratio (95 % confidence interval) 1.41 (1.24-1.60)],
      age >=35 years [1.17 (1.03-1.33)], and presence of hypertension [2.42 (1.93
      3.03)] were significant independent risk factors for abruptio placentae, while
      advancing gestation [0.67 (0.63-0.71)] decreased risk of abruptio placentae.
      Primiparity [odds ratio (95 % confidence interval) 4.06 (2.49-6.63)], age <20
      years [2.44 (1.07-5.58)], presence of hypertension [28.7 (20.5-40.1)], and
      advancing gestation [1.28 (1.11-1.47)] were significant independent risk factors
      for eclampsia. CONCLUSION: The use of uterotonics did not increase the risk of
      abruptio placentae and eclampsia.

PMID- 24292107
TI  - Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective
      when used as part of fracture liaison services or primary care screening.
AB  - SUMMARY: We identified that use of VFA may be cost-effective in either selected
      women from primary care or women attending after a low trauma fracture.
      INTRODUCTION: Lateral DXA scanning of the spine for vertebral fracture assessment
      (VFA) is used for research, but its wider role is unclear. We aimed to establish
      whether VFA is cost-effective in women based on two different scenarios:
      following a low-trauma fracture, and after screening of high-risk women
      identified in primary care. METHODS: The fracture cohort (FC) consisted of 377
      women and the primary care cohort (PCC) of 251. Vertebral fractures were
      identified on VFA images by quantitative morphometry (QM). Outcome was cost
      effectiveness of VFA, based on predicted change in clinical management defined as
      the identification of a vertebral fracture in a patient who otherwise falls below
      the threshold for treatment. FRAX treatment thresholds assessed were (1) 20/3 %
      thresholds and (2) National Osteoporosis Guidelines Group (NOGG) thresholds.
      RESULTS: As a result, 9.8 % from FC and 13.9 % from PCC were identified with
      vertebral fractures. Management was changed in 21 to 22/377 (5.6-5.8 %) in FC and
      12 to 26/251 (4.8-10.4 %) from PCC depending on which thresholds were used.
      Sensitivity analyses identified medication adherence as the assumption which most
      influenced the model. The best-estimate cost-per-QALY for use of VFA in FC was
      L3,243 for 20/3 threshold and L2,130 for NOGG; for PCC, this was L7,831 for 20/3
      and was cost-saving for NOGG. Further analyses to adjust for potential false
      positive vertebral fracture identification with QM showed VFA was no longer cost
      effective. CONCLUSION: VFA appears to be cost-effective in routine clinical
      practise, particularly when relatively inaccurate methods of identification of
      vertebral fractures are used such as QM.

PMID- 24292108
TI  - Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1-34)] therapy in the
      setting of chronic warfarin and glucocorticoid treatment.
AB  - Calciphylaxis occurs rarely in the absence of end stage renal disease.
      Predisposing factors for nonuremic calciphylaxis (NUC) include
      hyperparathyroidism, coagulopathies, connective tissue disease, liver disease,
      glucocorticoid use, and malignancy. Warfarin can facilitate vascular
      calcification by reducing vitamin K-dependent carboxylation of matrix-Gla
      proteins. An 86-year-old Caucasian woman with a history of polymyalgia
      rheumatica, two spontaneous deep venous thromboses (DVTs) and multiple fractures
      was treated with calcium, vitamin D, prednisone, and warfarin. The patient's low
      bone density was treated initially with estrogen, then oral bisphosphonate, which
      was discontinued due to upper gastrointestinal symptoms. Nasal calcitonin was
      initiated. After 10 years of calcitonin treatment, she was changed to
      teriparatide. Two months after initiating teriparatide, she developed lower
      extremity edema and painful erythematous nodular lesions on her calves
      bilaterally, that progressed to necrotic ulcers despite antibiotic therapy.
      Biopsy of the lesions showed calcification in the media of small blood vessels
      and subcutaneous fat with fat necrosis, consistent with calciphylaxis.
      Teriparatide was discontinued. Aggressive wound care, antibiotics, and
      intravenous zoledronic acid were initiated. With cessation of teriparatide
      therapy and intensive wound care, the patient's lesions resolved over 8 months.
      We report the first case of NUC precipitated by teriparatide therapy. Our patient
      had multiple underlying predisposing factors including a connective tissue
      disorder, glucocorticoid therapy, warfarin use, and possible underlying
      coagulopathy given her history of multiple DVTs. In such patients, alternative
      osteoporosis therapies may be preferred.

PMID- 24292109
TI  - Bile acids increase the activity of the epithelial Na+ channel.
AB  - The epithelial Na(+) channel (ENaC) is a key regulator of Na(+) absorption in
      various epithelia including the distal nephron and the distal colon. ENaC is a
      constitutively active channel, but its activity is modulated by a number of
      mechanisms. These include proteolytic activation, ubiquitination and cell surface
      expression, phosphorylation, intracellular Na(+) concentration, and shear stress.
      ENaC is related to the bile acid-sensitive ion channel (BASIC), a channel that is
      expressed in the epithelial cells of bile ducts. BASIC is activated by millimolar
      concentrations of extracellular bile acids. Bile acids are synthesized by the
      liver and secreted into the duodenum to aid lipolysis. A large fraction of the
      secreted bile acids is absorbed by the ileum and recirculated into the liver, but
      a small fraction passes the colon and is excreted. Bile acids can influence the
      ion transport processes in the intestinal tract including the colon. In this
      study, we show that various bile acids present in rat bile potently and
      reversibly increase the activity of rat ENaC expressed in Xenopus oocytes,
      suggesting that bile acids are natural modulators of ENaC activity. 

PMID- 24292110
TI  - [Evaluation of pulmonary artery stiffness using routine clinical imaging
      methods].
AB  - Recently, there has been much debate about pulmonary hypertension due to modern
      therapeutic options available. Arterial hypertension is frequently associated
      with stiffening of a given artery. The aim of the present review is to present
      clinical imaging methods for the evaluation of the function and stiffness of the
      pulmonary artery.

PMID- 24292111
TI  - [Optimal treatment of the axilla after positive sentinel lymph node biopsy in
      early invasive breast cancer. Early results of the OTOASOR trial].
AB  - INTRODUCTION: Sentinel lymph node biopsy alone has become an acceptable
      alternative to elective axillary lymph node dissection in patients with
      clinically node-negative early-stage breast cancer. Approximately 70 percent of
      the patients undergoing breast surgery develop side effects caused by the
      axillary lymph node dissection (axillary pain, shoulder stiffness, lymphedema and
      paresthesias). AIM: The current standard treatment is to perform completion
      axillary lymph node dissection in patients with positive sentinel lymph node
      biopsy. However, randomized clinical trials of axillary dissection versus
      axillary irradiation failed to show survival differences between the two types of
      axillary treatment. The National Institute of Oncology, Budapest conducted a
      single centre randomized clinical study. The OTOASOR (Optimal Treatment of the
      Axilla - Surgery or Radiotherapy) trial compares completion axillary lymph node
      dissection to axillary nodal irradiation in patients with sentinel lymph node
      positive primary invasive breast cancer. METHOD: Patients with primary invasive
      breast cancer (clinically lymph node negative and less than or equal to 3 cm in
      size) were randomized before surgery for completion axillary lymph node
      dissection (arm A-standard treatment) or axillary nodal irradiation (arm B
      investigational treatment). Sentinel lymph node biopsy was performed by the radio
      guided method. The use of blue-dye was optional. Sentinel lymph nodes were
      investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin
      staining. In the investigational treatment arm patients received 50Gy axillary
      nodal irradiation instead of completion axillary lymph node dissection. Adjuvant
      treatment was recommended and patients were followed up according to the actual
      institutional guidelines. RESULTS: Between August 2002 and June 2009, 2106
      patients were randomized for completion axillary lymph node dissection (1054
      patients) or axillary nodal irradiation (1052 patients). The two arms were well
      balanced according to the majority of main prognostic factors. Sentinel lymph
      node was identified in 2073 patients (98.4%) and was positive in 526 patients
      (25.4%). Fifty-two sentinel lymph node-positive patients were excluded from the
      study (protocol violation, patient's preference). Out of the remaining 474
      patients, 244 underwent completion axillary lymph node dissection and 230
      received axillary nodal irradiation according to randomization. The mean length
      of follow-up to the first event and the mean total length of follow-up were 41.9
      and 43.3 months, respectively, and there were no significant differences between
      the two arms. There was no significant difference in axillary recurrence between
      the two arms (0.82% in arm A and 1.3% in arm B). There was also no significant
      difference in terms of overall survival between the arms at the early stage
      follow-up. CONCLUSIONS: The authors conclude that after a mean follow-up of more
      than 40 months axillary nodal irradiation may control the disease in the axilla
      as effectively as completion axillary lymph node dissection and there was also no
      difference in terms of overall survival.

PMID- 24292112
TI  - [Efficacy of tumor necrosis factor-alpha inhibitors in fistulising perianal
      Crohn's disease].
AB  - INTRODUCTION: Tumor necrosis factor-alpha inhibitors are increasingly used in the
      treatment of severe Crohn's disease. AIM: The aim of the authors was to assess
      retrospectively the short and long term efficacy of tumor necrosis factor-alpha
      inhibitors in fistulising Crohn's disease. METHOD: Responses to therapy was
      determined using Crohn's Disease Activity Index, Perianal Disease Activity Index,
      the rate of complete fistula closure and the additional surgical procedures
      during biological therapy. RESULTS: After 12 weeks the perianal activity was
      decreased in more than 80% of the cases, and the complete remission rate was
      about 60%. After one year of therapy about one third of the patients had fistula
      closure, but after cessation of the biological therapy recurrence of fistulas was
      detected in every second patient. In most cases additional immunosuppressive
      therapy was necessary during biological treatment. During the one-year therapy
      period additional surgical treatments were performed in 45% of patients; seton
      insertion and abscess drainage were the most frequent procedures. CONCLUSIONS:
      Tumor necrosis factor-alpha inhibitor therapy is effective in the treatment of
      perianal Crohn's disease, however, additional immunosuppressive drugs and rectum
      sparing surgical procedures were necessary during the one-year treatment period.
      Because of the high rate of fistula recurrence, long term tumor necrosis factor
      alpha treatment may be useful.

PMID- 24292113
TI  - [Medical students of Hungary. A changing profession or feminisation?].
AB  - INTRODUCTION: Career motivations, professional socialization, as well as somatic
      and mental health of medical students have received a growing interest. AIM: To
      explore gender-related differences among medical students in the fields of career
      motivations, somatic and mental health, and stress factors. METHOD: Nationwide,
      cross-sectional, quantitative survey on a sample of medical students (n = 731).
      RESULTS: Female medical students choose their profession earlier, and their
      career motivations are more altruistic than their male colleagues. The lack of
      the role model is more typical for females. Female students have more
      psychosomatic disorders, and complain about more stress factors than males.
      Workload, sleeping disorders and emotional exhaustion are significantly higher
      among female medical students. CONCLUSIONS: The results show that health
      protection of female medical students may have a key role in the prevention of
      subsequent morbidity of female physicians in Hungary.

PMID- 24292114
TI  - [Acute cytomegalovirus infection-associated hemophagocytic syndrome in a patient
      treated with azathioprine].
AB  - The authors present the case of a 21-year-old woman with ulcerative colitis.
      Azathioprine treatment was complicated with pancytopenia and septic shock. Acute
      cytomegalovirus infection related to the immunosuppressive therapy, resulting in
      hemophagocytosis syndrome and neutropenic fever was diagnosed. Recovery was
      achieved by the administration of parenteral ganciclovir, broad spectrum
      antibiotic and complex intensive care.

PMID- 24292115
TI  - [Pathography of Richard Wagner (1813-1883)].

PMID- 24292118
TI  - A robust vision-based method for staircase detection and localization.
AB  - A robust vision-based staircase identification method is proposed, which
      comprises 2D staircase detection and 3D staircase localization. The 2D detector
      pre-screens the input image, and the 3D localization algorithm continues the task
      of retrieving geometry of the staircase on the reported region in the image. A
      novel set of principal component analysis-based Haar-like features are
      introduced, which extends the classical Haar-like features from local to global
      domain and are extremely efficient at rejecting non-object regions for the early
      stages of the cascade, and the Viola-Jones rapid object detection framework is
      improved to adapt the context of staircase detection, modifications have been
      made on the scanning scheme, multiple detections integrating scheme and the final
      detection evaluation metrics. The V-disparity concept is applied to detect the
      planar regions on the staircase surface and locate 3D planes quickly from
      disparity maps, and then, the 3D position of staircase is localized robustly.
      Finally, experiments show the performance of the proposed method. 

PMID- 24292117
TI  - Supramolecular photochirogenesis.
AB  - Supramolecular photochirogenesis is a rapidly growing interdisciplinary area of
      science at the boundary of photochemistry, asymmetric synthesis and
      supramolecular chemistry. The major advantage of supramolecular photochirogenesis
      over the conventional molecular one is entropic in origin, being achieved by
      preorganizing substrate(s) in the ground state and manipulating subsequent
      photochemical transformation by weak but non-transient interactions in chiral
      supramolecular media. The chirality transfer often becomes more efficient through
      the cooperative non-covalent interactions and the confinement by host in both
      ground and excited states. Thus, all of the ground- and excited-state events,
      including complexation stoichiometry and affinity, chiroptical properties,
      photophysical behaviour and photochemical reactivity, jointly play pivotal roles
      in supramolecular photochirogenesis. This may appear to cause complication but in
      reality expands the range of manipulable factors and available
      experimental/theoretical tools for elucidating the mechanism and controlling
      photochirogenic processes both thermodynamically and kinetically, from which some
      new concepts/methodologies unique to supramolecular photochemistry, such as non
      sensitizing catalytic photochirogenesis and wavelength-controlled
      photochirogenesis, have already been developed. In this review, we will discuss
      the recent progress and future perspective of supramolecular photochirogenesis. 

PMID- 24292119
TI  - Non-squamous cell carcinoma of the penis: single-center, 15-year experience.
AB  - PURPOSE: Penile cancer is a rare malignancy with less than 5 % being non-squamous
      cell carcinoma (SCC) primary malignancies. We report our 15-year experience of
      treating non-SCC penile cancer at a tertiary care cancer center. METHODS: We
      identified 12 patients with non-SCC of the penis from 1996 to 2012. Demographic
      and clinical data were abstracted, including histological type, surgical
      treatment, adjuvant therapy, and clinical course. RESULTS: Five patients had
      sarcoma (three leiomyosarcoma, one spindle cell carcinoma, and one epithelioid
      sarcoma), four had melanoma, two had extramammary Paget's disease (EPD), and one
      had sebaceous carcinoma. Median follow-up was 37.5 months (mean 45.8 months).
      Tumor staging for melanoma was pT1aN3, pTisNx, pTxNxM1b, and pT3bN0. Patients
      with melanoma were treated with penile sparing surgery; two are alive without
      disease, one is alive with disease, and one patient with metastasis at
      presentation died of disease at 16.3 months. The patients with sarcoma and deep
      seated or node-positive disease died of disease at a mean of 49.7 months. Two
      patients with EPD were treated with wide local excision of the lesions and were
      both pT1Nx. The remaining patient had sebaceous carcinoma treated with excisional
      biopsy and was free of disease at 32.0 months. CONCLUSIONS: Non-SCC of the penis
      is primarily treated surgically, with the goal of complete excision at the time
      of treatment. The utilization of lymphadenectomy is less clear in these
      malignancies, but aggressive approaches should be considered in appropriate
      patients. Tumor stage and nodal status are important in determining patient
      outcomes.

PMID- 24292122
TI  - Impaired long-term quality of life in survivors of severe sepsis : Chinese
      multicenter study over 6 years.
AB  - OBJECTIVES: The present study was undertaken to evaluate the long-term health
      related quality of life (HRQOL) as well as the employment status in survivors of
      severe sepsis up to 6 years afterwards. MATERIAL AND METHODS: From January 2003
      to December 2008 a total of 112 severe sepsis and 112 age, gender and Charlson
      comorbidity index-matched non-septic critically ill patients from 4 university
      hospital intensive care units (ICU) were enrolled in the study and 126 age and
      gender-matched community residents were interviewed as the community control
      group. RESULTS: A total of 66 (58.9 %) severe sepsis and 80 (71.4 %) non-sepsis
      critically ill patients survived during the long-term follow-up time. Between
      August and December 2010 a total of 75 patients including 42 survivors of severe
      sepsis and 33 critically ill controls completed the face-to-face interview. There
      were no differences in the long-term HRQOL in terms of Short-Form 36 criteria
      between severe sepsis and non-sepsis critically ill survivors. However, when
      compared with the community controls, HRQOL in survivors of severe sepsis showed
      a significantly and clinically meaningful decrease, with a lower physical
      functioning (p = 0.016), vitality (p = 0.037), role-emotional (p = 0.043), mental
      health (p = 0.038) and mental component scores (p = 0.042). In addition, the
      criteria returning to work at 1 year and at the time of interview in severe
      sepsis survivors were similar with those in critically ill survivors (60.5 % vs.
      70.0 %, p = 0.41 and, 71.1 % vs. 76.7 %, p = 0.602). CONCLUSIONS: The HRQOL in
      survivors of severe sepsis was impaired even up to 6 years after hospital
      discharge.

PMID- 24292123
TI  - [Perioperative approach to restless legs syndrome].
AB  - Restless legs syndrome (RLS) is one of the most common neurological disorders.
      The key feature is the urge to move, especially in the legs. New onset RLS can
      develop perioperatively or an existing RLS can be exacerbated. Severe insomnia,
      forced immobilization and acute iron deficiency are common trigger factors.
      Medicinal treatment can also be an important triggering or exacerbating factor.
      Drugs with dopamine antagonistic, serotonergic and opioid antagonistic effects
      should be avoided. The long-term medicinal treatment should be terminated as
      quickly as possible and if necessary bridged non-orally. For diseases which can
      be associated with secondary RLS a provocation or an exacerbation of RLS should
      be taken into consideration. This is particularly true for Parkinson's disease,
      diabetes mellitus, terminal renal insufficiency, spinal cord lesions and
      pregnancy. So far, there is not sufficient evidence that any form of anesthesia
      has a negative influence on RLS. 

PMID- 24292124
TI  - [Comments on: long-term cognitive impairment after intensive care therapy].

PMID- 24292125
TI  - Recent advances in production of succinic acid from lignocellulosic biomass.
AB  - Production of succinic acid via separate enzymatic hydrolysis and fermentation
      (SHF) and simultaneous saccharification and fermentation (SSF) are alternatives
      and are environmentally friendly processes. These processes have attained
      considerable positions in the industry with their own share of challenges and
      problems. The high-value succinic acid is extensively used in chemical, food,
      pharmaceutical, leather and textile industries and can be efficiently produced
      via several methods. Previously, succinic acid production via chemical synthesis
      from petrochemical or refined sugar has been the focus of interest of most
      reviewers. However, these expensive substrates have been recently replaced by
      alternative sustainable raw materials such as lignocellulosic biomass, which is
      cheap and abundantly available. Thus, this review focuses on succinic acid
      production utilizing lignocellulosic material as a potential substrate for SSF
      and SHF. SSF is an economical single-step process which can be a substitute for
      SHF - a two-step process where biomass is hydrolyzed in the first step and
      fermented in the second step. SSF of lignocellulosic biomass under optimum
      temperature and pH conditions results in the controlled release of sugar and
      simultaneous conversion into succinic acid by specific microorganisms, reducing
      reaction time and costs and increasing productivity. In addition, main process
      parameters which influence SHF and SSF processes such as batch and fed-batch
      fermentation conditions using different microbial strains are discussed in
      detail. 

PMID- 24292126
TI  - Sequel of jailed side branch.

PMID- 24292127
TI  - Red blood cell distribution width is longitudinally associated with mortality and
      anemia in heart failure patients.
AB  - BACKGROUND: Red blood cell distribution width (RDW) has been found to be an
      independent predictor for adverse outcome in patients with heart failure (HF),
      but there are no data on the association of longitudinal RDW with all-cause
      mortality and occurrence of anemia. METHODS AND RESULTS: 1,702 patients
      discharged from a previous admission for acute HF (AHF) were included. RDW was
      measured during the available longitudinal history of the patient. Joint modeling
      and Multistate Markov were used for the analysis. The median RDW at baseline was
      15.0% (IQR: 14.0-16.5), and 45.6% of patients had anemia. At a median follow-up
      of 1.5 years (IQR: 0.45-3.25), 713 patients died. The last RDW-trajectory value
      and cumulative RDW-trajectory mean were predictive of mortality (HR, 1.18; 95%
      CI: 1.12-1.24; and HR, 1.12; 95% CI: 1.08-1.16, respectively; P<0.001 for both).
      This effect, however, varied according the anemia status (P for
      interaction<0.001), being more pronounced in absence of anemia [HR=1.31 (95% CI:
      1.22-1.42) and HR=1.48 (95% CI: 1.33-1.64)] compared to those with anemia
      [HR=1.08 (95% CI: 1.04-1.13), 1.12 (95% CI: 1.06-1.18)]. Longitudinal RDW (per 1%
      increasing) was also independently associated with incident anemia [HR=1.10 (95%
      CI: 1.03-1.18) P=0.002]. CONCLUSIONS: Following an admission for AHF, higher
      longitudinal RDW values over time were associated to an increased risk for both
      developing anemia and dying. The effect on mortality was more pronounced among
      non-anemic patients.  

PMID- 24292128
TI  - Endovascular aortic repair increases vascular stiffness and alters cardiac
      structure and function.
AB  - BACKGROUND: Endovascular aortic repair (EVAR) is performed in patients with
      thoracic or abdominal aortic aneurysm because it is less invasive than
      conventional open repair. However, the effects of EVAR on vascular and cardiac
      function remain to be clarified. METHODS AND RESULTS: We studied the effects of
      EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for
      abdominal and/or thoracic aneurysm with preserved ejection fraction.
      Echocardiography and brachial-ankle pulse wave velocity (baPWV) data were
      collected before, 1 week, and 1 year after EVAR. Although no changes in blood
      pressure were found, baPWV, left ventricular mass index (LVMI), and left atrial
      volume index were significantly elevated at both post-op time periods after EVAR
      compared with baseline data. The changes in LVMI correlated with those in baPWV
      (R=0.32, P<0.05). Among the 22 patients who were successfully followed up, 13
      showed deterioration in exercise tolerance 1 year after EVAR. Diastolic wall
      strain, an index for LV distensibility, was lower at baseline in patients with
      worsening exercise tolerance than in those with unchanged tolerance. CONCLUSIONS:
      EVAR increased vascular stiffness and induced LV hypertrophy and diastolic
      dysfunction without a corresponding elevation of blood pressure in the acute and
      chronic phases. In addition, low LV distensibility at baseline was associated
      with the impairment of exercise tolerance. EVAR-induced stiffness of arteries
      leads to limited clinical symptoms.  

PMID- 24292120
TI  - The phosphopantetheinyl transferases: catalysis of a post-translational
      modification crucial for life.
AB  - Covering: up to 2013. Although holo-acyl carrier protein synthase, AcpS, a
      phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was
      not until the publication of the landmark paper by Lambalot et al. in 1996 that
      PPTases garnered wide-spread attention being classified as a distinct enzyme
      superfamily. In the past two decades an increasing number of papers have been
      published on PPTases ranging from identification, characterization, structure
      determination, mutagenesis, inhibition, and engineering in synthetic biology. In
      this review, we comprehensively discuss all current knowledge on this class of
      enzymes that post-translationally install a 4'-phosphopantetheine arm on various
      carrier proteins.

PMID- 24292129
TI  - Comparison of long-term outcome after endovascular therapy versus bypass surgery
      in claudication patients with Trans-Atlantic Inter-Society Consensus-II C and D
      femoropopliteal disease.
AB  - BACKGROUND: Although endovascular therapy (EVT) has advanced, few reports have
      compared EVT and bypass surgery in claudication patients with femoropopliteal
      disease. The present study used data from a multicenter registry in Japan to
      analyze outcomes of EVT and bypass surgery for claudication patients with Trans
      Atlantic Inter-Society Consensus (TASC)-II C and D femoropopliteal lesions.
      METHODS AND RESULTS: Of 1,156 patients who underwent revascularization, 696
      patients were treated for intermittent claudication. A total of 263 patients with
      femoropopliteal lesion were classified into TASC-II C and D. The primary and
      secondary patency rates of the EVT and bypass surgery groups were analyzed. The
      overall complication rate was 14.4% in the bypass surgery group and 3.5% in the
      EVT group (P<0.01). The 1- and 5-year primary patency rates were 82.1% and 69.4%
      in the bypass surgery group and 67.8% and 45.2% in the EVT group, respectively.
      Although the bypass surgery group had a higher primary patency rate than the EVT
      group (P<0.01, log-rank test), secondary patency rates did not differ
      significantly between the two groups. CONCLUSIONS: Although bypass surgery is
      clearly feasible for claudication patients with TASC-II C and D femoropopliteal
      disease, EVT is also a good option because of its lower complication rate and
      good secondary patency rate in patients in poor condition for bypass.  

PMID- 24292130
TI  - [Photo quiz: Dermatomycosis].

PMID- 24292131
TI  - [Photo quiz: Deep-seated mycosis].

PMID- 24292132
TI  - [Photo quiz: Basic mycology].

PMID- 24292133
TI  - [Diagnosis of invasive aspergillosis].

PMID- 24292134
TI  - [Molecular detection and identification for mycosis-fungal DNA extraction
      method].

PMID- 24292135
TI  - Treatment of onychomycosis using a 1064nm Nd:YAG laser.
AB  - We investigated the efficacy of 1064nm Nd:YAG laser for the treatment of
      onychomycosis caused by dermatophytes. The study population consisted of 12
      patients (6 male, 6 female ; average age 53.5 years), with onychomycosis
      confirmed by fungal culture and/or real-time PCR identification of the pathogen.
      The causative agent was identified as Trichophyton rubrum in 11 cases and a
      mixture of T. rubrum and T. mentagrophytes in 1 case. For each patient, laser
      treatment was given to a single hallux nail, with turbidity at baseline affecting
      <75% of the nail surface and thickness at baseline <3mm. Treatment was given in 3
      sessions at 4-week intervals, and nail turbidity was evaluated 3 and 6 months
      after the first laser treatment. After 6 months the efficacy results were as
      follows: 3 cases, turbidity significantly improved ( >70%) ; 2 cases, turbidity
      improved (50-70%), 1 case, turbidity slightly improved (30-50%) ; 5 cases, no
      change in turbidity (<30% improvement) ; and 1 case, turbidity worsened. Overall,
      the total lesion area with turbidity in 12 patients decreased from 664.4mm(2) to
      481.0mm(2), corresponding to a 27.6% improvement after treatment. Pain during
      laser treatment was well tolerated, and all patients underwent all 3 treatments.
      These results suggest that the 1064nm Nd:YAG laser could be a useful treatment
      alternative for patients with mild onychomycosis.

PMID- 24292136
TI  - Rapid molecular typing of Prototheca zopfii by high resolution melting real-time
      PCR (PCR-HRM).
AB  - Prototheca zopfii is an achlorophyllic alga that is ubiquitous around cow sheds.
      The alga is associated with bovine mastitis, which causes a reduction in milk
      production and secretion of thin watery milk containing white flakes. Isolates of
      P. zopfii from bovine mastitis were almost all identified as P. zopfii genotype
      2, suggesting that it is the main causative agent of bovine protothecal mastitis.
      The ability to differentiate between genotype 1 and genotype 2 is therefore very
      important for preventing bovine mastitis. In this study, high resolution melting
      real-time PCR (PCR-HRM) analysis of the protothecal 18S rDNA domain successfully
      differentiated between genotypes of P. zopfii in less than 3 hours, while
      conventional sequence analysis requires more than 48 hours to differentiate
      between genotypes. PCR-HRM analysis clustered P. zopfii genotype 1 isolates
      separately from P. zopfii genotype 2 isolates, indicating that this molecular
      typing method is an effective tool for rapidly diagnosing bovine protothecal
      mastitis.

PMID- 24292137
TI  - [Manual of laboratory procedures for medically important fungi (2013)].

PMID- 24292138
TI  - Scientific report on 5th Congress of Asia Pacific Society for Medical Mycology
      (APSMM 2013).

PMID- 24292139
TI  - Sensitivity enhancement of an electrochemical immunosensor through the
      electrocatalysis of magnetic bead-supported non-enzymatic labels.
AB  - An ultrasensitive non-enzymatic electrochemical carcinoembryonic antigen (CEA)
      immunosensor was fabricated by the immobilization of a monoclonal CEA antibody
      (anti-CEA) on a protein A (PA) attached-gold nanoparticles (AuNPs)-deposited
      electrochemically prepared polydopamine film (e-PD/AuNPs). Magnetic beads (MB)
      supported and CEA-conjugated multiple 3,3',5,5'-tetramethylbenzidine (TMB) was
      used as electrochemical labels. The detection was based on the measurements of
      the electrocatalyzed oxidation of ascorbic acid (AA) by the multiple TMB labels
      after competitive binding between MB/TMB-conjugated-CEA and free-CEA. The
      electrocatalyzed oxidation current of AA by TMB decreased with increasing
      concentration of the free-CEA as the amount of CEA/MB/TMB labels decreased at the
      immunosensor probe. The immunosensor surface was characterized using
      electrochemical impedance spectroscopy, Fourier transform infrared spectroscopy,
      quartz crystal microbalance, and scanning electron microscopy techniques. Cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV) techniques were used to
      monitor the electrocatalyzed response. The proposed immunosensor exhibited a wide
      linear dynamic range (1.0 pg/mL to 10.0 ng/mL), low detection limit (1.0+/-0.04
      pg/mL), good selectivity, and long-time stability. It was successfully applied to
      various CEA spiked human serum samples for the detection of CEA.

PMID- 24292140
TI  - Highly sensitive fluorescent immunosensor for detection of influenza virus based
      on Ag autocatalysis.
AB  - A versatile, ultrasensitive immunosensor for detection of influenza virus was
      designed by combining silver nanoparticles (Ag NPs) labeled antibodies with
      indirect fluorescence. A new technology using Ag-S covalent binding was applied
      for antibody labeling. Influenza A (H1N1) virus, as a subtype of influenza A
      virus that was the most common cause of human influenza (flu), was acted as the
      target antigen using sandwich type-immunoreactions on the high binding ELISA
      plates. The antibody-labeled Ag NPs were then released by acid solution to
      produce Ag(+) which can catalyze o-phenylenediamine (OPDA) oxidation to produce
      fluorescence for highly sensitive detection. Under the optimal conditions, it
      shows good linear relationship between fluorescence intensity and the logarithm
      of the concentration of H1N1 over the range of 1.0*10(-12)-1.0*10(-8) g mL(-1)
      with a detection limit (LOD, 3sigma) of 1.0*10(-13) g mL(-1). Results indicated
      that the proposed method give a good sensitivity and simple operation for
      detecting the influenza virus. This work also provided a promising potential for
      antigen detection by Ag NPs labeled, and the steps were easy to handle.

PMID- 24292141
TI  - DNAzyme-functionalized gold-palladium hybrid nanostructures for triple signal
      amplification of impedimetric immunosensor.
AB  - A highly sensitive and selective impedimetric immunosensor with triple signal
      amplification was designed for ultrasensitive detection of prostate-specific
      antigen (PSA) by using anti-PSA antibody and DNAzyme-functionalized gold
      palladium hybrid nanotags (Ab2-AuPd-DNA). The signal was amplified based on the
      Ab2-AuPd-DNA toward the catalytic precipitation of 4-choloro-1-naphthol (4-CN).
      DNAzyme (as a kind of peroxidase mimic) could catalyze the oxidation of 4-CN,
      whilst AuPd hybrid nanostructures could not only provide a large surface coverage
      for immobilization of biomolecules but also promote 4-CN oxidation to some
      extent. The produced insoluble benzo-4-chlorohexadienone via 4-CN was coated on
      the electrode surface, and hindered the electron transfer between the solution
      and the electrode, thereby increasing the Faradaic impedance of the base
      electrode. Three labeling strategies including Ab2-AuNP, Ab2-AuPd and Ab2-AuPd
      DNA were investigated for determination of PSA, and improved analytical features
      were obtained with the Ab2-AuPd-DNA strategy. Under optimal conditions, the
      dynamic concentration range of the impedimetric immunosensor spanned from 1.0 pg
      mL(-1) to 50 ng mL(-1) PSA with a detection limit of 0.73 pg mL(-1). Intra- and
      inter-assay coefficients of variation were below 8.5% and 9.5%, respectively.
      Importantly, no significant differences at the 0.05 significance level were
      encountered in the analysis of 6 clinical serum specimens and 6 diluted standards
      between the impedimetric immunosensor and the commercialized
      electrochemiluminescent method for PSA detection.

PMID- 24292142
TI  - A novel HBV genotypes detecting system combined with microfluidic chip, loop
      mediated isothermal amplification and GMR sensors.
AB  - Genotyping of hepatitis B virus (HBV) can be used for clinical effective
      therapeutic drug-selection. A novel microfluidic biochip for HBV genotyping has
      been fabricated, for the first time, integrating loop-mediated isothermal
      amplification (LAMP), line probes assay (LiPA) and giant magnetoresistive (GMR)
      sensors. Coupling LAMP with LiPA in microfluidic chip shortened reaction time
      substantially, and combining LAMP with GMR sensor enabled limit of detection to
      attain 10 copies mL(-1) target HBV DNA molecules in 1 h. Furthermore, the
      independent designed GMR sensors and microfluidic chip can decrease manufacturing
      cost and patient's test-cost, and facilitate GMR detector repeating use for
      signal detection. In addition, the detection system has a lower background signal
      owing to application of superparamagnetic nanoclusters. And it can be expected to
      use for multiple target molecules synchronous detection in microfluidic chip
      based on a characteristic of stationary reaction temperature of LAMP. In
      conclusion, the neoteric detecting system is well suitable for quick genotyping
      diagnosis of clinical HBV and other homothetic biomolecule detection in
      biological and medical fields.

PMID- 24292143
TI  - Microconductometric immunosensor for label-free and sensitive detection of Gram
      negative bacteria.
AB  - Blood safety is a global health goal. In developed countries, bacterial
      contamination of platelet concentrates is the highest infectious risk in
      transfusion despite the current preventive strategies. We aimed to develop a
      conductometric biosensor for the generic, rapid and sensitive detection of Gram
      negative bacteria. Our strategy is based on immunosensors: addressable magnetic
      nanoparticles coupled with anti-LPS antibodies were used for the generic capture
      of Gram-negative bacteria. Bacterial capture was characterized by impedancemetric
      and microscopic measurements. The results obtained with conductometric
      measurements allowed real-time, sensitive detection of Escherichia coli or
      Serratia marcescens cultures from 1 to 10(3) CFU mL(-1). The ability of the
      immunosensor to detect Gram negative bacteria was also tested on clinically
      relevant strains. The conductometric immunosensor allowed the direct detection of
      10-10(3) CFU mL(-1) of Pseudomonas aeruginosa and Acinetobacter baumannii strains
      that were undetectable using standard immunoblot methods. Results showed that the
      conductometric response was not inhibited in 1% serum.

PMID- 24292144
TI  - Biosensor analysis of natural and artificial sweeteners in intact taste
      epithelium.
AB  - Sweeteners are commonly used as food additives in our daily life, which, however,
      have been causing a number of undesirable diseases since the last century.
      Therefore, the detection and quantification of sweeteners are of great value for
      food safety. In this study, we used a taste biosensor to measure and analyze
      different sweeteners, both natural and artificial sweeteners included.
      Electrophysiological activities from taste epithelium were detected by the multi
      channel biosensors and analyzed with spatiotemporal methods. The longtime signal
      result showed different temporal-frequency properties with stimulations of
      individual sweeteners such as glucose, sucrose, saccharin, and cyclamate, while
      the multi-channel results in our study revealed the spatial expression of taste
      epithelium to sweet stimuli. Furthermore, in the analysis of sweetener with
      different concentrations, the result showed obvious dose-dependent increases in
      signal responses of the taste epithelium, which indicated promising applications
      in sweetness evaluation. Besides, the mixture experiment of two natural
      sweeteners with a similar functional unit (glucose and sucrose) presented two
      signal patterns, which turned out to be similar with responses of each individual
      stimulus involved. The biosensor analysis of common sweeteners provided new
      approaches for both natural and artificial sweeteners evaluation. 

PMID- 24292145
TI  - Current trends in the development of the electrochemiluminescent immunosensors.
AB  - This review presents a general picture of the current trends and developments
      (2008-2013) related to electrochemiluminescence-based immunosensors. It briefly
      covers the milestones of qualitative changes in the field of
      electrochemiluminescent immunosensors; the peculiarities of the
      electrochemiluminescent immunoassay formats; the basic mechanisms of ECL
      detection, main features of early and ongoing approaches in
      electrochemiluminescent immunoassay commercial instruments, and the recent
      developments in fabrication of solid-state electrochemiluminescent immunosensors.
      Moreover, systematized data on biomarkers, immunoassay formats, and novel types
      of electrochemiluminescent label and immobilization support, such as
      semiconductor nanocrystals, porous noble metals, graphene, TiO2 nanotube arrays,
      metal-organic composites, multiwall carbon nanotubes, liposomes,
      photolummonescent carbone nanocrystals are presented as a table. Considerable
      efforts have also been devoted towards the following two key points: multiplexing
      analysis (multi-label, and the multianalyte strategies) and integration in
      microfluidic lab-on-paper devices with capabilities for point-to-care
      diagnostics. An immuno-like electrochemiluminescent sensor (based on synthetic
      receptors-molecularly imprinted polymers), as a new alternative to traditional
      electrochemiluminescent immunoassay is highlighted. Future perspectives and
      possible challenges in this rapidly developing area are also discussed. 

PMID- 24292146
TI  - Inelastic electron scattering from a helical potential: transverse polarization
      and the structure factor in the single scattering approximation.
AB  - We analyze single scattering of unpolarized photoelectrons through a monolayer of
      chiral molecules modeled by a continuous hardcore helix and spin-orbit coupling.
      The molecular helix is represented by an optical contact potential containing a
      non-hermitian component describing inelastic events. Transmitted photoelectrons
      are transversely polarized at optimal angles, and separated into up and down spin
      with up to 20% efficiency. Such a process involves the interference of both spin
      orbit and inelastic strengths, that are parameterized quantitatively to recent
      experiments in chiral self-assembled monolayers (SAMs). The structure factor of
      the model chiral molecule shows the energy dependence of the differential cross
      section which decays strongly as energy increases. Larger incident momenta reduce
      axial deviations from the forward direction and the spin-orbit interaction
      becomes less effective. Transverse electron polarization is then restricted to a
      characteristic energy window. 

PMID- 24292147
TI  - A near infrared fluorescence resonance energy transfer based aptamer biosensor
      for insulin detection in human plasma.
AB  - A new FRET model using near-infrared quantum-dots (NIR-QDs) and oxidized carbon
      nanoparticles (OCNPs) as the energy donor and acceptor was constructed and
      designed for insulin detection in complex human plasma. 

PMID- 24292148
TI  - Molecular evaluation of proliferative-phase endometrium may provide insight about
      the underlying causes of infertility in women with endometriosis.
AB  - PURPOSE: To determine if endometrial gene expression is different in women with
      endometriosis-related infertility and fertile women. METHODS: Prospective study
      of mid-follicular phase endometrium in 47 subjects in two phases: microarray
      study of 10 infertile women with endometriosis and five fertile controls, and a
      quantitative real-time PCR (qRT-PCR) study of 27 infertile women with
      endometriosis and 15 fertile controls. Gene expression was determined by DNA
      microarray, and qRT-PCR used for 12 "promising" genes based on the microarray
      analysis. RESULTS: Compared to fertile controls, women with stage I-II
      endometriosis had 23, and women with stage III-IV had 35 genes that were
      significantly up- or down-regulated by microarray. However, using qRT-PCR, only
      chemokine ligand (CXCL) 13 was significantly down-regulated and somatostatin was
      significantly up-regulated with early endometriosis, and only CXCL 14 was
      significantly down-regulated with advanced endometriosis compared to fertile
      controls. CONCLUSIONS: Our findings indicate that the pattern of gene expression
      in proliferative-phase endometrium is different when comparing tissue from
      patients with endometriosis versus fertile controls. Recognition of these
      endometrial alterations could be helpful to diagnose and stage endometriosis, and
      may provide insight to explain why conception rates are low in women with
      endometriosis.

PMID- 24292149
TI  - Comparison of Iodine-125 seeds implantation and afterloading radiotherapy in
      murine models of human cervical cancer.
AB  - OBJECTIVE: To compare the efficacies and side effects of Iodine-125 (125I) seeds
      implantation with afterloading radiotherapy on tumor xenografts derived from Hela
      cells. METHODS: Mice bearing Hela cells were randomly divided into three groups:
      two therapeutic groups receiving four 125I seeds implantation and afterloading
      therapy, respectively, and the one control group without any intervention.
      Comparisons were evaluated in aspects of curative efficacies (tumor volume, tumor
      inhibition rate and metastasis) and side effects (body weight, ovarian endocrine
      functions, skin lesion surrounding the tumor). RESULTS: The xenografts tumor
      volume of therapeutic groups were significantly smaller than that of controls(p <
      0.05),both of the 125I seeds implantation and afterloading therapy showed
      excellent tumor inhibition rate. Furthermore, 125I seeds implantation had milder
      side effects on skin, weight loss, ovarian endocrine functions. CONCLUSIONS:
      (125)I seed implantation may be an alternative minimally invasive therapy for
      cervical cancer.

PMID- 24292153
TI  - Identification of N-homocysteinylation sites in plasma proteins.
AB  - A protocol for the identification of N-homocysteinylation sites in plasma
      proteins is described. Human plasma or purified fibrinogen is subjected to
      trypsin digestion and analysis of N-Hcy-peptides by liquid chromatography/mass
      spectroscopy (LC/MS). Human fibrinogen is isolated from the plasma by the glycine
      precipitation method. Identification of N-Hcy-Lys-peptides in tryptic digests of
      in vivo-derived samples is facilitated by the use of N-Hcy-albumin and N-Hcy
      fibrinogen synthesized in vitro from commercially available human proteins. This
      protocol allows identification of N-homocysteinylation sites at Lys4, Lys12,
      Lys137, and Lys525 in albumin directly in trypsin-digested human serum samples. N
      Hcy-Lys562, N-Hcy-Lys344, and N-Hcy-Lys385 were identified in human fibrinogen
      from patients with cystathionine beta-synthase deficiency. The protocol can be
      completed in 4 days.

PMID- 24292151
TI  - Discovery of chlamydial peptidoglycan reveals bacteria with murein sacculi but
      without FtsZ.
AB  - Chlamydiae are important pathogens and symbionts with unique cell biological
      features. They lack the cell-division protein FtsZ, and the existence of
      peptidoglycan (PG) in their cell wall has been highly controversial. FtsZ and PG
      together function in orchestrating cell division and maintaining cell shape in
      almost all other bacteria. Using electron cryotomography, mass spectrometry and
      fluorescent labelling dyes, here we show that some environmental chlamydiae have
      cell wall sacculi consisting of a novel PG type. Treatment with fosfomycin (a PG
      synthesis inhibitor) leads to lower infection rates and aberrant cell shapes,
      suggesting that PG synthesis is crucial for the chlamydial life cycle. Our
      findings demonstrate for the first time the presence of PG in a member of the
      Chlamydiae. They also present a unique example of a bacterium with a PG sacculus
      but without FtsZ, challenging the current hypothesis that it is the absence of a
      cell wall that renders FtsZ non-essential. 

PMID- 24292154
TI  - The abundance of fecal Faecalibacterium prausnitzii in relation to obesity and
      gender in Chinese adults.
AB  - The influence of gender and obesity on the abundance of human colonic
      Feacalibacterium prausnitzii is currently unclear. We collected fecal samples
      from 54 obese and 54 sex- and age-matched normal-weight Chinese adults and
      quantified the fecal F. prausnitzii as percentage of 16S rRNA gene copies of F.
      prausnitzii accounting to that of total gut bacteria with quantitative PCR. The
      fecal F. prausnitzii amount was not significantly different between obese and
      lean subjects. Men possessed significantly lower level of fecal F. prausnitzii
      than women, and the significant and positive correlation of fecal F. prausnitzii
      quantity with fasting glucose level was observed in men, not in women. Our
      results suggest that the gender effect, in addition to other factors including
      the geographic location, ethnicity, diet and gut transit times of study subjects,
      has to be considered when studying the relationship between gut F. prausnitzii
      and diseases. 

PMID- 24292152
TI  - New paradigm for tumor theranostic methodology using bacteria-based microrobot.
AB  - We propose a bacteria-based microrobot (bacteriobot) based on a new fusion
      paradigm for theranostic activities against solid tumors. We develop a
      bacteriobot using the strong attachment of bacteria to Cy5.5-coated polystyrene
      microbeads due to the high-affinity interaction between biotin and streptavidin.
      The chemotactic responses of the bacteria and the bacteriobots to the
      concentration gradients of lysates or spheroids of solid tumors can be detected
      as the migration of the bacteria and/or the bacteriobots out of the central
      region toward the side regions in a chemotactic microfluidic chamber. The
      bacteriobots showed higher migration velocity toward tumor cell lysates or
      spheroids than toward normal cells. In addition, when only the bacteriobots were
      injected to the CT-26 tumor mouse model, Cy5.5 signal was detected from the tumor
      site of the mouse model. In-vitro and in-vivo tests verified that the
      bacteriobots had chemotactic motility and tumor targeting ability. The new
      microrobot paradigm in which bacteria act as microactuators and microsensors to
      deliver microstructures to tumors can be considered a new theranostic methodology
      for targeting and treating solid tumors. 

PMID- 24292155
TI  - A split-face, evaluator-blind randomized study on the early effects of Q-switched
      Nd:YAG laser plus Er:YAG micropeel (combined therapy) versus Q-switched Nd:YAG
      alone in light solar lentigines in Asians.
AB  - Solar lentigines are a common sign of aging in Asians, who often asked for
      treatment. Various lasers, including Q-switched Nd:YAG and Er:YAG, have been
      adopted, but the results are not always satisfactory, especially for those who
      are relatively light in color. Our objective was to compare the early effects as
      well as side effects of Q-switched Nd:YAG laser plus Er:YAG micropeel (combined
      therapy) with those of Q-switched Nd:YAG laser (QSNY) alone in light solar
      lentigines in Asians. This was a split-face, evaluator-blind, randomized
      controlled study. A single session of treatment was performed on Asian patients
      with light facial lentigines. A combined treatment with QSNY and Er:YAG micropeel
      was allocated to one half of the face, and QSNY alone to the other half. The
      response to therapy was evaluated by two independent dermatologists, with
      standardized photographs taken 2 weeks and 1 month after the laser treatment.
      Patients' satisfaction and preference in treatment were also assessed. Fifteen
      patients completed the study and were analyzed. Overall, a reduction in pigment
      was observed with both treatment arms during the study period. The degree of
      pigment reduction following combined therapy and QSNY alone was similar at 2
      weeks' follow-up (  = 0.433). However, due to the higher incidence of
      postinflammatory hyperpigmentation (PIH) with combined therapy (73.3 vs 40%), the
      degree of pigment reduction in the combined side of the face was found
      significantly lower than that of the QSNY-alone side at 1-month follow-up (P =
      0.014). Although our study results show that both combined therapy and QSNY alone
      are capable of reducing pigmentation, QSNY alone is considered to have more
      favorable qualities than combined treatment for light solar lentigines in Asians.

PMID- 24292156
TI  - Home-based palliative care: a systematic literature review of the self-reported
      unmet needs of patients and carers.
AB  - BACKGROUND: There have been many studies on the unmet needs of palliative care
      patients and carers from the perspective of bereaved caregivers. However, the
      unmet needs of palliative care patients and carers from the perspective of
      current patients and their carers have received little research attention. AIM:
      As home-based services have become one of the main delivery models of palliative
      care, the aim of this review was to describe, evaluate and summarise the
      literature on the unmet needs of palliative home care patients and carers.
      DESIGN: The systematic review of qualitative and quantitative studies was
      conducted in accordance with the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines. DATA SOURCES: PubMed, CINAHL, Embase,
      MEDLINE, PsycINFO, AMED and CareSearch were searched to find empirical studies on
      the self-reported unmet needs of palliative home care patients and carers.
      RESULTS: Nine qualitative studies, three quantitative studies and three mixed
      design studies were identified. The most frequently reported unmet need was
      effective communication with health-care professionals, the lack of which
      negatively impacted on the care received by patients and carers. Physical care
      needs were met, which indicates that the examined palliative home care services
      were delivering satisfactory care in this domain, but lacking in other areas.
      CONCLUSIONS: The focus therefore should be on improving other aspects of patient
      care, including communication by health professionals to prevent or reduce
      suffering in areas such as psychosocial domains. Valid and reliable quantitative
      measures of unmet needs in palliative care are needed to examine this area more
      rigorously.

PMID- 24292157
TI  - End-of-life care and achieving preferences for place of death in England: results
      of a population-based survey using the VOICES-SF questionnaire.
AB  - BACKGROUND/AIM: Health policy places emphasis on enabling patients to die in
      their place of choice, and increasing the proportion of home deaths. In this
      article, we seek to explore reported preferences for place of death and
      experiences of care in a population-based sample of deaths from all causes.
      DESIGN: Self-completion post-bereavement survey. SETTING/PARTICIPANTS: Census of
      deaths registered in two health districts between October 2009 and April 2010.
      Views of Informal Carers - Evaluation of Services Short Form was sent to each
      informant (n = 1422; usually bereaved relative) 6-12 months post-bereavement.
      RESULTS: Response was 33%. In all, 35.7% of respondents reported that the
      deceased said where they wanted to die, and 49.3% of these were reported to
      achieve this. Whilist 73.9% of those who were reported to have a preference cited
      home as the preferred place, only 13.3% of the sample died at home. Cancer
      patients were more likely to be reported to achieve preferences than patients
      with other conditions (p < .01). Being reported to have a record of preferences
      for place of death increased the likelihood of dying at home (odds ratio =
      22.10). When rating care in the last 2 days, respondents were more likely to rate
      'excellent' or 'good' for nursing care (p < .01), relief of pain (p < .01) and
      other symptoms (p < .01), emotional support (p < .01) and privacy of patient's
      environment (p < .01) if their relative died in their preferred place.
      CONCLUSIONS: More work is needed to encourage people to talk about their
      preferences at the end of life: this should not be restricted to those known to
      be dying. Increasing knowledge and achievement of preferences for place of death
      may also improve end-of-life care.

PMID- 24292158
TI  - When do people with dementia die peacefully? An analysis of data collected
      prospectively in long-term care settings.
AB  - BACKGROUND: Little is known about dying peacefully with dementia in long-term
      care facilities. Dying peacefully may be influenced by characteristics of the
      palliative care provided and characteristics of the long-term care setting. If
      so, dying peacefully may serve as a quality indicator for palliative care in
      dementia. AIM: This study aims to describe whether residents with dementia in
      Dutch long-term care facilities die peacefully and to assess which
      characteristics of the resident, the palliative care provided and the facilities
      are associated with dying peacefully. DESIGN AND SETTING: We analysed existing
      data from the Dutch End of Life in Dementia study, collected between January 2007
      and July 2010 in 34 long-term care facilities in the Netherlands. We used
      descriptive statistics and Generalised Estimating Equation models. RESULTS: The
      sample consisted of 233 residents with dementia. Family members indicated that
      the resident died peacefully in 56% of cases. This percentage ranged from 17% to
      80% across facilities. Residents were more likely to die peacefully if they had
      an optimistic attitude, if family found that there were enough nurses available
      and if residents died in facilities with a moderate (versus no) perceived
      influence of religious affiliation on end-of-life decision-making policies.
      CONCLUSIONS: Only half of the residents with dementia in Dutch long-term care
      facilities die peacefully, as perceived by relatives. In addition to residents'
      optimistic attitude, facility characteristics are associated with dying
      peacefully, which suggests that 'the percentage of relatives who indicate that
      the patient died peacefully' can function as a quality indicator.

PMID- 24292159
TI  - Comparison of US panel vendors for online surveys.
AB  - BACKGROUND: Despite the increasing use of panel surveys, little is known about
      the differences in data quality across panels. OBJECTIVE: The aim of this study
      was to characterize panel survey companies and their respondents based on (1) the
      timeliness of response by panelists, (2) the reliability of the demographic
      information they self-report, and (3) the generalizability of the characteristics
      of panelists to the US general population. A secondary objective was to highlight
      several issues to consider when selecting a panel vendor. METHODS: We recruited a
      sample of US adults from 7 panel vendors using identical quotas and online
      surveys. All vendors met prespecified inclusion criteria. Panels were compared on
      the basis of how long the respondents took to complete the survey from time of
      initial invitation. To validate respondent identity, this study examined the
      proportion of consented respondents who failed to meet the technical criteria,
      failed to complete the screener questions, and provided discordant responses.
      Finally, characteristics of the respondents were compared to US census data and
      to the characteristics of other panels. RESULTS: Across the 7 panel vendors, 2%
      to 9% of panelists responded within 2 days of invitation; however, approximately
      20% of the respondents failed the screener, largely because of the discordance
      between self-reported birth date and the birth date in panel entry data. Although
      geographic characteristics largely agreed with US Census estimates, each sample
      underrepresented adults who did not graduate from high school and/or had annual
      incomes less than US $15,000. Except for 1 vendor, panel vendor samples
      overlapped one another by approximately 20% (ie, 1 in 5 respondents participated
      through 2 or more panel vendors). CONCLUSIONS: The results of this head-to-head
      comparison provide potential benchmarks in panel quality. The issues to consider
      when selecting panel vendors include responsiveness, failure to maintain
      sociodemographic diversity and validated data, and potential overlap between
      panels.

PMID- 24292161
TI  - [Loss of visual acuity after cataract surgery].

PMID- 24292160
TI  - Aryl hydrocarbon receptor (AHR) in the cnidarian Nematostella vectensis:
      comparative expression, protein interactions, and ligand binding.
AB  - The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per
      ARNT-Sim (bHLH-PAS) family of transcription factors and has diverse roles in
      development, physiology, and environmental sensing in bilaterian animals.
      Studying the expression of conserved genes and function of proteins in outgroups
      to protostomes and deuterostomes assists in understanding the antiquity of gene
      function and deciphering lineage-specific differences in these bilaterian clades.
      We describe the developmental expression of AHR from the sea anemone Nematostella
      vectensis and compare its expression with three other members of the bHLH-PAS
      family (AHR nuclear translocator (ARNT), Cycle, and a proto-Single
      Minded/Trachealess). NvAHR expression was highest early in the larval stage with
      spatial expression in the basal portion of the ectoderm that became increasingly
      restricted to the oral pole with concentrated expression in tentacles of the
      juvenile polyp. The other bHLH-PAS genes showed a divergent expression pattern in
      later larval stages and polyps, in which gene expression was concentrated in the
      aboral end, with broader expression in the endoderm later in development. In co
      immunoprecipitation assays, we found no evidence for heterodimerization of AHR
      with ARNT, contrary to the conservation of this specific interaction in all
      bilaterians studied to date. Similar to results with other invertebrate AHRs but
      in contrast to vertebrate AHRs, NvAHR failed to bind two prototypical xenobiotic
      AHR ligands (2,3,7,8-tetrachlorodibenzo-p-dioxin, beta-naphthoflavone). Together,
      our data suggest that AHR's original function in Eumetazoa likely involved
      developmental patterning, potentially of neural tissue. The role of
      heterodimerization in the function of AHR may have arisen after the cnidarian
      bilaterian ancestor. The absence of xenobiotic binding to NvAHR further supports
      a hypothesis for a derived role of this protein in chemical sensing within the
      chordates. 

PMID- 24292162
TI  - Characteristics of corneal topographic and pachymetric patterns in patients with
      pellucid marginal corneal degeneration.
AB  - PURPOSE: To determine the characteristics of the shape of the cornea in patients
      with pellucid marginal corneal degeneration (PMD) and to compare these
      characteristics to those of eyes with keratoconus and eyes of normal subjects.
      METHODS: This was a retrospective, cross-sectional case-series in which 49 eyes
      of 33 patients with PMD, 51 eyes of 51 patients with keratoconus and 53 eyes of
      53 subjects with normal corneas (controls) were examined and compared. For all
      eyes, we obtained the topographic patterns of the axial power maps, anterior and
      posterior elevation maps and pachymetric maps using a rotating Scheimpflug
      camera. The eyes were classified into the respective patterns by visual
      inspection of these maps. RESULTS: In eyes with PMD, the most common axial power
      map pattern was the crab claw pattern (78 %) followed by the inferior steepening
      pattern (18 %). In eyes with keratoconus, the most common pattern was the
      inferior steepening pattern (67 %). The most common pattern in the elevation maps
      for both surfaces was the asymmetric island in eyes with PMD and keratoconus.
      Although the decentered pattern, including the decentered oval (27 %) and
      decentered round (20 %) pattern, on pachymetric map was specific to eyes with
      PMD, the incidence of these patterns was relatively low. CONCLUSIONS: The
      similarity in the topographic and pachymetric patterns in eyes with PMD and
      keratoconus suggests that they may be a continuity of the same disorder with
      different phenotypes.

PMID- 24292164
TI  - Desmoplastic fibroma of the rib with cystic change: a case report and literature
      review.
AB  - Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor
      microscopically composed of well-differentiated myofibroblasts with abundant
      dense collagen deposition. The most common sites are the long tubular bones and
      mandible. To our knowledge, only five cases of DF in the ribs have been reported.
      Here, we report a case of DF in this rare location with unusual radiological
      findings. A 40-year-old man presented with a 4-year history of swelling of the
      right chest wall. Radiographs revealed a mass at the right 9th rib, and computed
      tomography demonstrated a mass of 14 * 12 * 8 cm at the right 9th rib with
      expanded cystic change and marked calcification that appeared to have arisen from
      the bone. Open biopsy suggested DF. Total excision was performed, and the chest
      wall was reconstructed. The surgical specimen was a yellowish tumor with
      multilocular cystic change containing a viscous liquid. The tumor was composed of
      a proliferation of less-atypical spindle-shaped cells in a collagenous
      background. The cystic change was observed in the extra-osseous lesion. No beta
      catenin cytoplasmic/nuclear accumulation was detected, and no beta-catenin or
      GNAS genetic mutations were detected. A final diagnosis of DF was made on the
      basis of the pathological and radiological findings. The patient was successfully
      treated with total excision of the tumor with no evidence of recurrence 6 months
      after surgery. 

PMID- 24292165
TI  - Results from the Hawaii domestic violence fatality review, 2000-2009.
AB  - BACKGROUND: Patterns of domestic violence fatalities and agency responses in
      Hawaii have not been explicated. METHODS: Retrospective reviews of events leading
      up to domestic violence related fatalities in Hawaii were assessed from 45
      adjudicated cases that resulted in 62 fatalities for the ten year period from
      2000-2009. RESULTS: Almost one-half of the fatalities were homicide/suicide
      combinations. Females were disproportionately more likely to be fatal victims of
      domestic violence relative to their proportion in the population. Those aged 21
      40 years and those over 80 years were more likely to be fatal victims of domestic
      violence, relative to their proportion in the population. Filipinas and 'Other"
      ethnic groups are disproportionately more likely to be fatal victims of domestic
      violence while Native Hawaiians and Japanese are less likely to be fatal victims,
      relative to their proportions in the population. In more than two-thirds of the
      cases, the victim had made some attempt to leave the relationship prior to the
      fatality. CONCLUSIONS: In the majority of cases there was agency involvement in
      some form: either the victim alone or the perpetrator alone, or both. However,
      less than one-third (31.1%) of the cases over the past ten years had
      documentation of prior violence from medical reports, so this may be an area to
      further document and address domestic violence.

PMID- 24292163
TI  - Inflammation and pancreatic cancer: disease promoter and new therapeutic target.
AB  - Chronic inflammation has a certain impact on the carcinogenesis of the digestive
      organs. The characteristic tissue structure of pancreatic cancer, desmoplasia,
      results from inflammatory processes induced by cancer cells and stromal cells.
      Concerning the progression of pancreatic cancer, recent research has clarified
      the pivotal role of tumor-stromal interaction, which promotes the development of
      an invasive phenotype of cancer and provides survival advantages against
      chemotherapeutic agents or immune surveillance. Tumor stromal cells such as
      pancreatic stellate cells and immune cells establish a microenvironment that
      protects cancer cells through complex interactions. The microenvironment of
      pancreatic cancer acts as a niche for pancreatic cancer stem cells from which
      therapy-resistance and disease recurrence develop. Inhibition of the stromal
      functions or restoration of the immune reaction against cancer cells has
      therapeutic benefits that enhance the efficacy of conventional therapies. Some of
      the recent advances in this field are now under evaluation in clinical settings,
      but many problems must be overcome to establish a radical therapy for pancreatic
      cancer. This review summarizes current knowledge about the tumor-promoting
      stromal functions, immune system modulation and therapeutic strategies targeting
      tumor-stromal interactions in pancreatic cancer. 

PMID- 24292166
TI  - Mechanism of stabilization of dicalcium silicate solid solution with aluminium.
AB  - Stoichiometric dicalcium silicate, Ca2SiO4, displays a well-known polymorphism
      with temperature. When this phase is doped by a range of elements, belite, one of
      the main phases of cements, is generated. Here, we thoroughly study the aluminum
      doping of dicalcium silicate. This type of study is important for cement
      characterization and also from a basic point of view. Ca2Si(1-2x)Al(2x)O(4-x)?(x)
      (x = 0, 0.010, 0.014, 0.03) has been prepared and studied by X-ray powder
      diffraction and the Rietveld method. The limiting composition has been
      established as Ca2Si0.972Al0.028O3.986?0.014. The (27)Al MAS NMR band located
      close to ~-70 ppm is ascribed to tetrahedral environments, in agreement with the
      proposed aliovalent Si/Al atomic substitution mechanism. Thermal analysis
      measurements under a wet atmosphere indirectly confirm the increase of oxygen
      vacancies as the amount of incorporated protons increases with the aluminium
      content. A thorough electrical characterization has been carried out including
      overall conductivity measurements under wet and dry atmospheres and conductivity
      as a function of the oxygen partial pressure. The samples show oxide anion
      conductivity with a small p-type electronic contribution under oxidizing
      conditions. These compounds display a very important proton contribution to the
      overall conductivities under humidified atmospheres.

PMID- 24292168
TI  - Thermally/hydrolytically stable covalent organic frameworks from a rigid
      macrocyclic host.
AB  - Two new 2D COFs were synthesized from triformylcyclotrianisylene, which show not
      only thermal stability but also hydrolytic stability. CTV-COF-1 with smaller pore
      size stored a high hydrogen level of 1.3 wt% at low pressure, while CTV-COF-2
      with larger pore size showed superior carbon dioxide uptake, up to 250 cm(3) g(
      1) at 298 K and 50 bar. 

PMID- 24292167
TI  - Tachycardia-induced cardiomyopathy due to repetitive monomorphic ventricular
      ectopy in association with isolated left ventricular non-compaction.
AB  - Isolated left ventricular non-compaction is a rare genetic disorder manifesting
      mainly with heart failure, ventricular arrhythmias and systemic embolism.
      Isolated ventricular tachycardia originating from the right ventricular outflow
      tract is an arrhythmia that can be treated medically and/or by radiofrequency
      catheter ablation. Here, we report a case of an asymptomatic 16-year-old boy with
      a new diagnosis of dilated cardiomyopathy, left ventricular noncompaction and
      right ventricular outflow tract tachycardia. Electrophysiological studies and
      radiofrequency ablation of the right ventricular outflow tract tachycardia
      resulted in normalisation of left ventricular systolic function. This is the
      first case reporting left ventricular non-compaction in association with
      tachycardia-induced cardiomyopathy secondary to repetitive monomorphic right
      ventricular outflow tract tachycardia. 

PMID- 24292169
TI  - [Toward development of innovative diagnostic/therapeutic system (theranostics)
      using nanotechnologies].

PMID- 24292170
TI  - [Novel dianostics and therapeutics with ultrasound technologies and
      nanotechnologies].
AB  - Ultrasound is a good tool for theranostics due to have multi-potency both of
      diagnostics with sonography and therapeutics with high intensity focused
      ultrasound (HIFU). In addition, microbubbles and nanobubbles are utilized as not
      only contrast imaging agent but also enhancer of drug and gene delivery by
      combination of ultrasound. Recently, we developed novel liposomal nanobubbles
      (Bubble liposomes) which were containing perfluoropropane. Bubble liposomes
      induced jet stream by low intensity ultrasound exposure and resulted in enhancing
      permeability of cell membrane. This phenomenon has been utilized as driving force
      for drug and gene delivery. On the other hand, the combination of Bubble
      liposomes and high intensity ultrasound induces strong jet stream and increase
      temperature. This condition can directly damage to tumor cells, we are applying
      this for cancer therapy. Therefore, their combination has potency for various
      cancer therapies such as gene therapy, immunotherapy and hyperthermia. In this
      review, we discuss about cancer therapy by the combination of Bubble liposomes
      and ultrasound.

PMID- 24292171
TI  - [Application of ultrasound-enhanced gene and drug delivery to the ocular tissue].
AB  - Visual images provide an immensely rich source of information about the external
      world. Eye has characteristic structure sensory cells are arranged along the eye
      wall, and is filled inside with vitreous body. In recent years, intravitreal
      injection of anti-vascular endothelial growth factor (VEGF) agent had widely
      spread, and numerous number of patients who suffered ocular angiogenic disease
      such as diabetic retinopathy, age-related macular degeneration and retinal
      vascular occlusion for the disease, were treated and spared the blindness.
      Vitreous cavity was regarded as reservoir of drug, intravitreal injection is
      thought a sort of drug delivery. However, with regard to the administration of a
      selective drug deliver, it has not yet been solved. Our aim is to establish a new
      method of gene transfer, drug delivery using low-energy ultrasound to the eye, to
      date, we confirmed drug and gene deliver to the ocular tissue such as cornea,
      conjunctiva and retina with high efficiency. In addition, tissue damage was
      minimal. We have also shown that ultrasound irradiation with combination of a
      microbubbles or bubble liposome could be introduced drug and gene more
      effectively. Based on these knowledge, we will focus on development of a new
      device for intraocular ultrasound exposure and potential for therapeutic
      application of ultrasound to humans retinal disease such as retinal artery
      obstruction.

PMID- 24292172
TI  - [Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent
      for theranostic system].
AB  - We applied a polymeric micelle carrier system for the targeting of a magnetic
      resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast
      agent exhibited a long circulation characteristic in blood, and considerable
      amount of the contrast agent was found to accumulate in colon 26 solid tumor by
      the EPR effect. The signal intensities of tumor area showed 2-folds increase in
      T1-weighted images at 24 h after i.v. injection. To observe enhancement of the
      EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent
      for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced
      tumor accumulation of the contrast agent. Interestingly, very high signal
      intensity in tumor region was found at 24 h after the contrast agent injection in
      Cderiv pretreated mice. The contrast agent visualized a microenvironmental change
      in tumor. These results indicate that the contrast agent exhibits potential use
      for tumor diagnostic agent. To combine with a polymeric micelle carrier system
      for therapeutic agent, the usage of the combination makes a new concept of
      "theranostic" for a better cancer treatment.

PMID- 24292173
TI  - [Supramolecular nanomachines for sugar responsive insulin release systems].
AB  - Cyclodextrins (CyDs) are cyclic oligosaccharides composed of 6, 7, or 8
      glucopyranoside units, named alpha-, beta-, or gamma-CD, respectively. CyDs
      consist of a hydrophobic cavity in which hydrophobic molecules are encapsulated
      to form an inclusion complex. CyDs are widely used in pharmaceutical applications
      because they function as nanocapsules to improve the stability and solubility of
      drugs. Recently, CyDs have attracted much attention as for use as components of
      supramolecular nanostructures that are particularly attractive because of their
      unique structures. We modified CyDs with phenylboronic acid (PBA), which forms
      covalent bonds with the diol groups of sugar, and used the resulting PBA-CyDs to
      prepare supramolecular nanomachines that undergo structural transformation in the
      presence of a chemical signal in the form of a sugar. PBA-alpha-CyD formed a
      supramolecular polymer that showed consecutive intermolecular interactions
      between PBA and the cavity of another PBA-alpha-CyD, whereas PBA-beta-CyD formed
      head-to-head dimers in which one PBA moiety was encapsulated in the other. These
      supramolecular nanostructures disintegrated in the presence of sugars because of
      the structural change in the PBA moiety and loss of the driving force of the
      supramolecular assembly. These features of disintegration can be potentially used
      to prepare a nanomachine that would act as a sugar-responsive insulin release
      system. Currently, we are studying sugar-responsive nanomachines composed of
      PEGylated insulin and PBA-gamma-CyD.

PMID- 24292174
TI  - [Development of high boron content liposomes and their promising antitumor effect
      for neutron capture therapy].
AB  - High accumulation and selective delivery of boron into tumor tissue are the
      most important requirements to achieve the efficient cell-killing effect of boron
      neutron capture therapy (BNCT) that relies on the nuclear reaction of two
      essentially nontoxic species, boron-10 ((10)B) and thermal neutrons in boron
      loaded tissues. Recent development of boron cluster lipids and their liposomal
      boron delivery system (BDS) are summarized in this article. Boron compounds that
      have no affinity to tumor can potentially be delivered to tumor tissues by
      liposomes, therefore, liposomal BDS would be one of the most attractive
      approaches for efficient BNCT of various cancers. There are two approaches for
      BDS: encapsulation of boron compounds into liposomes and incorporation of boron
      conjugated lipids into the liposomal bilayer. The combination of both approaches
      has a potential for reduction of the total dose of liposomes without reducing the
      efficacy of BNCT. 

PMID- 24292175
TI  - [School-based education on medicine for the promotion of self-medication--current
      condition and the role of pharmaceutical sciences].

PMID- 24292176
TI  - [Education of medicines in school education of Japan].
AB  - World Health Organization (WHO) indicated that recognition of the responsibility
      of individuals for their own health and awareness that professional care for
      minor ailments is often unnecessary were important points of view for "Self
      Medication" in "Guidelines for the Regulatory Assessment of Medicinal Products
      for Use in Self-Medication" published in 2000. In Japan, educational curriculum
      in each school is formulated by "the Courses of Study". Education for health at
      junior and senior high school is mainly carried out in "Health and Physical
      Education" class. The objectives are to enable students to develop qualities and
      abilities to appropriately manage and improve their health throughout their lives
      through understanding of health and safety in personal and social life. This idea
      is common with self-medication at a basic concept level. The previous Courses of
      Study were revised in 2008 and 2009. They described about medicine for senior but
      not junior high school. The interim report of "The Central Council for Education"
      in 2005 pointed out that understanding about effects/side effects by medicines,
      and abilities to use them appropriately are one of minimal qualities that all
      children must acquire. Due to revision of the Pharmaceutical Affairs Law in 2006,
      the necessity of endeavoring to widespread knowledge and enlighten about proper
      use of medicines in school education was considered. Since the new Courses of
      Study in the junior high school shows content that medicines should be used
      properly, it is thought that educational frame of medicines for children is going
      into new era in Japan.

PMID- 24292177
TI  - [The education on medicines will change Japanese medical care].
AB  - Teaching the three health principles and proper use of medicines are the basis of
      education on medicines. Before seeking prescription drugs, day-to-day health
      management is important. It is also important to understand that if a minor
      ailment persists, self-treatment with over-the-counter medications should be
      attempted. Since medications are double-edged swords, their proper use is the
      responsibility of patients to minimize the risk and maximize the effectiveness.
      This awareness should be taught during education on how to use medicines. A
      better understanding of medicines and fostering awareness through education on
      medicines will contribute to reductions in healthcare costs and promote the
      health of patients when they participate in their own care and learn how to self
      medicate.

PMID- 24292178
TI  - [Guidance for education on medicines in school].
AB  - To promote the education on medicines in school, guidance is, as a rule, to be
      given in the health education of the Subject, "Health and Physical Education"
      indicated as a curriculum standard in lower and upper secondary school, and in
      the health guidance, which carry out in Special Activities and Integrated
      Studies, etc. Guidance is mainly carried by the teacher for health and physical
      in health education and school nurse teacher (yogo teacher) in health guidance.
      In health education we have only limited school hours, and generally use the text
      book. Some teachers feel resistance to teach medicines because of needs on the
      special knowledge, however teachers should deal with medicines based on
      curriculum standard. School pharmacist is a member of school, and has a special
      knowledge for medicines, and he/she can support teachers as a provider of
      teaching materials, an adviser, and for a guest teacher. It is important for
      school pharmacist to understand the contents indicated in curriculum standard and
      to use glossary to be able to understand for children. In the guidance of health,
      it is not necessary to teach based on curriculum standard, and it can deal with
      advanced contents on medicines. However it is important to understand for
      children what are appropriate contents according to the development stage. To use
      the packages and instructions for medicines provided at home are good materials
      for children to have interest the medicines in their guidance. The objectives of
      education on medicines enable children to cultivate practical abilities for the
      maintenance and improvement of health.

PMID- 24292179
TI  - [Establishment of a "correct use of medicine" educational program for health and
      physical education at junior high schools].
AB  - Under new courses of study, medicine-related content has been incorporated into
      health and physical education at junior high schools, and classes on the "Correct
      use of medicine" began as part of this content in 2012. Based on the "School
      Health and Safety Law" implemented in April 2009, health guidance provided by
      school physicians, pharmacists, and dentists has also been incorporated. This has
      raised expectations that educational programs concerning the "Correct use of
      medicine" could be effectively implemented through cooperation between school
      pharmacists and health and physical education teachers. In order to clarify
      current knowledge and awareness regarding the "Correct use of medicine" among
      students, as well as the guidance provided at schools, we conducted a training
      workshop for teachers at elementary and junior high schools in Gifu City. Based
      on the results, we developed a "Correct use of medicine" educational program. We
      then presented this program in a class with 40 third-year junior high school
      students on January 31, 2012. It consisted of an introduction (7 min), a
      development portion (35 min), and a conclusion (8 min). After the class, a
      question and answer session was held with observers (n=11) and a questionnaire
      survey, which resulted in high evaluations, was conducted on the students.
      Comments including concern over the large volume of educational content and the
      need to raise awareness were heard, but the results of the questionnaire survey
      showed that many students found the class content useful and interesting.

PMID- 24292180
TI  - [Toward a new era of pharmacological therapeutics].

PMID- 24292181
TI  - [Biological significance and metabolic activation of vitamin K].
AB  - Natural vitamin K is found in two forms: a plant form, phylloquinone (PK) and
      bacterial forms, menaquinones (MKs). PK is a major form of dietary vitamin K;
      however, the most prevalent form of vitamin K in animals and humans is
      menaquinone-4 (MK-4). Despite its high concentrations, the origin of MK-4 is yet
      to be defined. It is postulated that PK is converted into MK-4 and accumulates in
      extrahepatic tissues. The molecular mechanisms for these conversion reactions
      have been unclear. To identify the MK-4 biosynthetic enzyme, we screened the
      human genome database for prenylation enzyme. We found UbiA prenyltransferase
      domain containing 1 (UBIAD1), a human homologue of Escherichia coli
      prenyltransferase menA. The short interfering RNA against the UBIAD1 gene
      inhibited the conversion of deuterium-labelled vitamin K derivatives into
      deuterium-labelled-MK-4 (MK-4-d7) in human cells. We confirmed that the UBIAD1
      gene encodes an MK-4 biosynthetic enzyme through its expression and conversion of
      deuterium-labelled vitamin K derivatives into MK-4-d7 in insect cells infected
      with UBIAD1 baculovirus. UBIAD1 was localized in endoplasmic reticulum. Our
      results show that UBIAD1 is a human MK-4 biosynthetic enzyme. This identification
      will permit more effective decisions to be made about vitamin K intake and bone
      health.

PMID- 24292182
TI  - [Elucidation of dysfunctional mechanisms of retinal circulation in the rat models
      of glaucoma and exploration of novel therapeutic drugs].
AB  - In recent times, glaucoma has become the leading cause of acquired blindness
      among the Japanese. As visual disorders markedly decrease the quality of life
      (QOL), it is important to develop new strategies for preventing the onset of and
      delaying the progression of glaucoma. Glaucoma has long since been recognized as
      a serious disease caused by increased intraocular pressure and subsequent injury
      and death of the neuronal retinal cells. Therefore, numerous studies have focused
      on the mechanisms that damage neuronal cells and on the drugs that possess
      protective effects in reversing this damage. However, injury to the retinal
      vasculature has been recently shown in animal models of glaucoma. Hence, thus
      far, only few papers have been published on retinal circulation in glaucoma.
      These study results have indicated that retinal circulation is altered in
      glaucoma and that this vascular abnormality may be the cause of and/or may
      accelerate retinal degeneration. In this report, we have attempted to elucidate
      the mechanisms of retinal circulation and explore novel drugs for the treatment
      of retinal circulation disorders. We have also introduced here our previous
      research results on retinal circulation. We reported that the drugs that improved
      retinal circulation, by intravitreal injection, in the rat model of glaucoma also
      inhibited retinal nerve injury, thereby representing possibilities that they
      might be novel candidate drugs for glaucoma prevention and treatment.

PMID- 24292183
TI  - [Enhanced Ca2+-sensing receptor function in pulmonary hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a rare, progressive, and fetal disease.
      The five-year survival rate after diagnosis is ~50%. In Japan, PAH is listed in
      the Specified Rare and Intractable Diseases. Pulmonary vascular remodeling and
      sustained pulmonary vasoconstriction are the major causes for the elevated
      pulmonary vascular resistance (PVR) in PAH. The pathogenic mechanisms involved in
      the pulmonary vascular abnormalities in PAH remain unclear. Sustained
      vasoconstriction and vascular remodeling owing to proliferation of pulmonary
      arterial smooth muscle cells (PASMCs) are key pathogenic events that lead to
      early morbidity and mortality. These events have been closely linked to Ca(2+)
      mobilization and signaling in PASMCs. An increase in cytosolic Ca(2+)
      concentration ([Ca(2+)]cyt) in PASMCs is an important stimulus for pulmonary
      vasoconstriction and cell proliferation which subsequently cause pulmonary
      vascular wall thickening followed by the increase in PVR. Increased resting
      [Ca(2+)]cyt and enhanced Ca(2+) influx have been implicated in PASMCs from PAH
      patients, but precise therapeutic targets to interrupt these signal pathways have
      not been identified. We recently found that the extracellular Ca(2+)-sensing
      receptor (CaSR), a G protein-coupled receptor (GPCR), is upregulated in PASMCs
      from patients with idiopathic pulmonary arterial hypertension (IPAH). In
      addition, blockage of the CaSR with an antagonist (NPS2143) prevents the
      development of pulmonary hypertension and right ventricular hypertrophy in animal
      models of pulmonary hypertension. The functionally upregulated CaSR in PASMCs is
      a novel pathogenic mechanism contributing to the augmented Ca(2+) signaling and
      excessive cell proliferation in IPAH. Targeting CaSR in PASMCs may help develop
      novel therapeutic approach for PAH.

PMID- 24292184
TI  - [Pharmaceutical basic researches aiming at clinical applications].

PMID- 24292185
TI  - [From basic principles to clinical applications on transcutaneous vaccine].
AB  - The recent vigorous transnational migration of people and materials reflecting
      the development of transportation facilities, changes in social structure, and
      war disasters has increased the global spread of emerging and re-emerging
      infectious diseases. Vaccine, which is the major fundamental prophylaxis against
      infectious diseases, has greatly contributed to the maintenance and improvement
      of human health worldwide. However, the disadvantages of conventional injection
      systems hamper the speedy mass-vaccination and the global distribution of
      vaccines. Transcutaneous immunization systems, which are easy-to-use and low
      invasive methods of vaccination, have the potential to overcome certain issues
      associated with injectable vaccinations. In this review, we provide an outline of
      recent trends in the development of techniques for the transcutaneous delivery of
      vaccine antigens. We also introduce basic and clinical research involving our
      transcutaneous immunization systems that incorporate self-dissolving microneedle
      patch.

PMID- 24292187
TI  - [In vitro tumorigenicity tests for process control of health care products
      derived from human induced pluripotent stem cells].
AB  - The goal of pharmaceutical sciences is to deliver effective and safe medicinal
      products to patients. To achieve this goal, we need to ensure the efficacy,
      safety and quality of the products. Currently, many attempts are made to utilize
      human induced pluripotent stem cells (hiPSCs) in regenerative medicine/cell
      therapy. There are significant obstacles, however, preventing the clinical use of
      hiPSC-derived products. One of the most obvious safety issues is the presence of
      residual undifferentiated cells that have tumorigenic potential. Therefore, the
      assessment and control of the tumorigenicity of hiPSC-derived products is
      essential in order to prevent tumor development by residual pluripotent stem
      cells after implantation. We recently examined three in vitro assay methods to
      detect undifferentiated cells: soft agar colony formation assay, flow cytometry
      assay and quantitative real-time polymerase chain reaction assay (qRT-PCR).
      Although the soft agar colony formation assay was unable to detect hiPSCs, the
      flow cytometry assay using anti-TRA-1-60 antibody detected 0.1% undifferentiated
      hiPSCs that were spiked in primary retinal pigment epithelial (RPE) cells.
      Moreover, qRT-PCR with a specific probe and primers was found to detect a trace
      amount of LIN28 mRNA, which is equivalent to that present in a mixture of a
      single hiPSC and 5.0*10(4) RPE cells. Our findings provide highly sensitive and
      quantitative in vitro assays essential for facilitating safety profiling of hiPSC
      derived RPE cells for their clinical use. 

PMID- 24292186
TI  - [Biomarker exploration and its clinical use].
AB  - Biomarkers are useful tools as indicators/predictors of disease severity and drug
      responsiveness, and thus, are expected to make drug development more efficient
      and to accelerate proper use of approved drugs. Many academic achievements on
      biomarkers have been reported, but only several biomarkers are used in drug
      development and clinical settings. We first show our results on the
      pharmacogenomic analysis of the anti-cancer drug irinotecan and of Stevens
      Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). UGT1A1*6 and *28
      were significantly associated with altered pharmacokinetics of an irinotecan
      metabolite, SN-38, and with increased frequency of severe neutropenia. HLA* 58:01
      and HLA-B*15:11/HLA-A*31:01 were associated with SJS/TEN by allopurinol and
      carbamazepine, respectively. Our papers have been cited in the package inserts of
      irinotecan and allopurinol. In addition to these genomic biomarkers, metabolomic
      biomarkers, which can reflect the disease phenotype and drug responsiveness, have
      been exploring for 12 major diseases in Japan, as a part of a multi-omics team
      with multi-national centers. In animal models of dilated cardiomyopathy and
      Alzheimer's disease, we found several changes in lipid metabolite levels in the
      diseased tissues. Moreover, two oxidized fatty acids were correlatively changed
      in the brain and plasma from Alzheimer's model mice before its onset, and thus,
      could be candidates for predictive biomarkers. Finally, we propose/discuss
      several key issues for academic researches on biomarker discovery and
      development, especially for newly coming researchers in the field of
      pharmaceutical sciences. We hope that this review would help novel biomarker
      identification and qualification in Japan.

PMID- 24292188
TI  - [Molecular targeting and translational research for new therapeutic strategies on
      Alzheimer's disease].
AB  - Alzheimer's disease (AD) is the most common cause of dementia. AD treatments
      currently approved are commonly regarded as purely symptomatic. Therefore,
      development of effective disease modifying treatments is eagerly required.
      Pathological hallmarks of AD brain include amyloid-beta (Abeta) accumulation,
      neurofibrillary tangle (NFT), synaptic loss, and neurodegeneration. Understanding
      of AD pathogenesis provides deep insight into the therapeutic approach for AD. In
      this review, we introduce our current translational researches for new
      therapeutic strategies against AD. We recently revealed that a key molecule for
      actin assembly, Wiscott-Aldrich syndrome protein family verprolin-homologous
      protein (WAVE), is accumulated into NFT in an Abeta pathology-dependent manner.
      Because synaptic function is maintained by precise regulation of actin assembly,
      abnormal accumulation of WAVE induced by Abeta pathology may expand the NFT
      pathology to synaptic dysfunction. These results imply that lowering of brain
      Abeta at the early stage of AD pathogenesis is a promising therapeutic approach.
      As the approach for the elimination of brain Abeta, we have studied microglial
      Abeta phagocytosis and proposed its therapeutic application for AD treatment. We
      demonstrated that anti-Abeta antibody and galantamine promote microglial Abeta
      phagocytosis by binding to Fc receptors and nicotinic acetylcholine receptors on
      microglia, respectively. On the other hand, we demonstrated that the
      transplantation with microglia effectively eliminate brain Abeta and microglia
      like Abeta phagocytic cells were successfully prepared from bone marrow derived
      cells by the stimulation with macrophage colony-stimulating factor. Thus, we have
      studied cell therapeutic strategy aim at its clinical application for AD
      treatment by the activation of endogenous microglia and transplantation of
      exogenous microglia-like Abeta phagocytic cells.

PMID- 24292189
TI  - [Regulation of expression, function, and inflammatory responses of innate immune
      receptor Toll-like receptor-2 (TLR2) during inflammatory responses against
      infection].
AB  - Toll-like receptor-2 (TLR2) is one of the important innate immune receptors that
      play an important role in recognizing the pathogens and producing inflammatory
      cytokines. In this review, we focus on the regulatory mechanisms of expression,
      function and inflammatory responses of TLR2 during pathogenic infection in innate
      immune cells. We first showed that nontypeable Haemophilus influenzae (NTHi), an
      important human pathogen that exacerbates otitis media and chronic obstructive
      pulmonary diseases (COPD), induces inflammatory responses through activation of
      NF-kappaB via two distinct signals, NIK-IKKalpha/beta-IkappaBalpha and MKK3/6-p38
      pathways. Moreover, TLR2 was greatly up-regulated by NTHi through the positive
      IKK-IkappaBalpha-dependent NF-kappaB pathway and the negative MKK3/6
      p38alpha/beta pathway. Importantly, glucocorticoids synergistically enhance NTHi
      induced TLR2 up-regulation likely via a negative cross-talk with the inhibitory
      p38 MAPK. The results provide novel insights into the role of glucocorticoids in
      regulating host defense and innate immune responses through TLR2 regulation. We
      next focused on the pathogenesis of cystic fibrosis (CF), a common lethal
      inherited disorder characterized by recurrent pulmonary infections and
      obstruction caused by chronic mucus hypersecretion and inflammation. We
      demonstrated an increased expression of TLR2, due to an enhanced DNA de
      methylation and Sp1-dependent transcriptional activation in CF epithelial cells.
      Furthermore, a Th17 cytokine IL-17A synergistically increased TLR2 signal through
      an enhancement of p38 phosphorylation. These studies suggest the importance of
      TLR2 and IL-17 signals in the pathogenesis of CF. Finally, by focusing on
      neutrophils and CF airway epithelial cells, we identified curcumin as a potent
      inhibitor of TLR2-mediated inflammatory responses.

PMID- 24292190
TI  - [Effect of heat transfer in the packages on the stability of thiamine nitrate
      under uncontrolled temperature conditions].
AB  - To accurately predict the stability of thiamine nitrate as a model drug in
      pharmaceutical products under uncontrolled temperature conditions, the average
      reaction rate constant was determined, taking into account the heat transfer from
      the atmosphere to the product. The stability tests of thiamine nitrate in the
      three packages with different heat transfers were performed under non-isothermal
      conditions. The stability data observed were compared with the predictions based
      on a newly developed method, showing that the stability was well predicted by the
      method involving the heat transfer. By contrast, there were some deviations
      observed from the predicted data, without considering heat transfer in the
      packages with low heat transfer. The above-mentioned result clearly shows that
      heat transfer should be considered to ensure accurate prediction of the stability
      of commercial pharmaceutical products under non-isothermal atmospheres.

PMID- 24292191
TI  - [Identification of the immunogenic outer membrane proteins of relapsing fever
      Borrelia].
AB  - Borrelia duttonii, a causative agent of relapsing fever, is transmitted between
      the distinct microenvironments of the vector tick, Ornithodoros moubata, and a
      mammalian host. We identified the total and membrane fraction proteins of B.
      duttonii strain Ly isolated from a patient in Tanzania by using two-dimensional
      gel electrophoresis with matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS). The analyses of the total and membrane
      fractions from bacterial cultures incubated at 37 degrees C identified 68 and 15
      proteins, respectively. Since spirochaete clearance in mice is associated with an
      immunoglobulin M (IgM) and immunoglobulin G3 (IgG3)-mediated response, immunoblot
      analyses were used to identify the proteins reactive with IgM and IgG3 of gerbil
      serum against B. duttonii strain Ly. The outcome showed that six proteins
      (antigen p83/100, membrane-associated protein P66 (P66), flagellar filament outer
      layer protein, hypothetical protein BDU_412, vlp protein gamma subfamily (gamma
      Vlp) and flagellin (FlaB)) were identified against IgM, and four (antigen
      p83/100, P66, gamma-Vlp and FlaB) of the six proteins also reacted with IgG3. It
      is believed that these proteins are immunodominant antigens for the host immune
      response. Some of these immunogenic proteins might be used as molecular
      diagnostic tools in the study of relapsing fever in Tanzania.

PMID- 24292192
TI  - [Neoadjuvant chemotherapy or primary surgery for colorectal liver metastases. Pro
      adjuvant chemotherapy].
AB  - Medicinal treatment of colorectal cancer liver metastases has undergone
      significant developments in the past two decades. Cytotoxic treatment regimens
      have demonstrated greater efficacy and contributed to a significant improvement
      in survival. Perioperative therapy with FOLFOX has demonstrated progression-free
      survival benefits in resectable colorectal liver metastases in a prospective
      randomized controlled trial. The safety of perioperative chemotherapy was found
      to be acceptable and only a few patients showed initial progression. In general,
      preoperative chemotherapy should not extend beyond 3-4 months to avoid
      chemotherapy-associated liver damage. For patients with borderline resectable
      metastases, a response to chemotherapy can establish secondary resectability.
      Combinations of cytotoxic drugs are adequate in this situation. The addition of
      bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies for tumors
      without RAS mutations are reasonable choices for a better response and improved
      survival outcome. It is crucial that all treatment decisions for systemic
      colorectal liver metastases include correct definitions of treatment goals and
      endpoints and are derived based on appropriate multidisciplinary considerations. 

PMID- 24292193
TI  - [HIV prophylaxis kits. A concept for emergency treatment in the context of
      postexposure prophylaxis].
AB  - Occupational transmission of HIV among healthcare personnel is rare but has
      repeatedly been published in the literature. Early initiation of postexposure HIV
      prophylaxis (HIV-PEP) is crucial to prevent virus transmission. For this reason
      the need for HIV-PEP has to be evaluated immediately and if necessary, started as
      soon as possible. This article presents an early intervention program in a
      university hospital which enables healthcare personnel immediate 24/7/365 access
      to a HIV-PEP prophylaxis kit following occupational HIV exposure. 

PMID- 24292194
TI  - Natural product-derived pharmacological modulators of Nrf2/ARE pathway for
      chronic diseases.
AB  - Covering: 2000 to 2013. Oxidative stress is the central component of chronic
      diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response
      element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes
      and enzymes in response to oxidative stress and treatment with certain dietary
      phytochemicals. Herein, we classify bioactive compounds derived from natural
      products that are Nrf2/ARE pathway activators and recapitulate the molecular
      mechanisms for inducing Nrf2 to provide favorable effects in experimental models
      of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has
      emerged as promising strategy against multi-drug resistance thereby improving the
      treatment efficacy. We have also enlisted natural product-derived inhibitors of
      Nrf2/ARE pathway.

PMID- 24292196
TI  - Disruption of paired-associate learning in rat offspring perinatally exposed to
      dioxins.
AB  - The prevalence of cognitive abnormalities in children has partly been ascribed to
      environmental chemical exposure. Appropriate animal models and tools for
      evaluating higher brain function are required to examine this problem. A recently
      developed behavioral test in which rats learn six unique flavor-location pairs in
      a test arena was used to evaluate paired-associate learning, a hallmark of the
      higher cognitive function that is essential to language learning in humans.
      Pregnant Long-Evans rats were dosed by gavage with 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) or 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) at a dose of 0, 200,
      or 800 ng/kg (referred as Control, TCDD-200, TCDD-800, TBDD-200, or TBDD-800,
      hereafter) on gestational day 15, and the offspring was tested during adulthood.
      Paired-associate learning was found to be impaired in the TCDD-200 and TBDD-200
      groups, but not in either group exposed to 800 ng/kg, the observations of which
      were ensured by non-cued trials. As for the emotional aspect, during habituation,
      the TCDD-200 and TBDD-200 groups showed significantly longer latencies to enter
      the test arena from a start box than the Control, TCDD-800, and TBDD-800 groups,
      suggesting that the TCDD-200 and TBDD-200 groups manifested anxiety-like
      behavior. Thus, both the chlorinated dioxin and its brominated congener affected
      higher brain function to a similar extent in a nearly identical manner. Use of
      the behavioral test that can evaluate paired-associate learning in rats
      demonstrated that in utero and lactational exposure to not only TCDD but also
      TBDD perturbed higher brain function in rat offspring in a nonmonotonic manner.

PMID- 24292195
TI  - Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new
      recurrently-mutated genes and molecular subgroups.
AB  - Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical
      subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions
      where tobacco-chewing is common. Exome sequencing (n=50) and recurrence testing
      (n=60) reveals that some significantly and frequently altered genes are specific
      to OSCC-GB (USP9X, MLL4, ARID2, UNC13C and TRPM3), while some others are shared
      with HNSCC (for example, TP53, FAT1, CASP8, HRAS and NOTCH1). We also find new
      genes with recurrent amplifications (for example, DROSHA, YAP1) or homozygous
      deletions (for example, DDX3X) in OSCC-GB. We find a high proportion of C>G
      transversions among tobacco users with high numbers of mutations. Many pathways
      that are enriched for genomic alterations are specific to OSCC-GB. Our work
      reveals molecular subtypes with distinctive mutational profiles such as patients
      predominantly harbouring mutations in CASP8 with or without mutations in FAT1.
      Mean duration of disease-free survival is significantly elevated in some
      molecular subgroups. These findings open new avenues for biological
      characterization and exploration of therapies. 

PMID- 24292197
TI  - Temperature profiles of 980- and 1,470-nm endovenous laser ablation, endovenous
      radiofrequency ablation and endovenous steam ablation.
AB  - Endovenous thermal ablation (EVTA) techniques are very effective for the
      treatment of varicose veins, but their exact working mechanism is still not well
      documented. The lack of knowledge of mechanistic properties has led to a variety
      of EVTA protocols and a commercially driven dissemination of new or modified
      techniques without robust scientific evidence. The aim of this study is to
      compare temperature profiles of 980-and 1,470-nm endovenous laser ablation
      (EVLA), segmental radiofrequency ablation (RFA), and endovenous steam ablation
      (EVSA). In an experimental setting, temperature measurements were performed using
      thermocouples; raw potato was used to mimic a vein wall. Two laser wavelengths
      (980 and 1,470 nm) were used with tulip-tip fibers and 1,470 nm also with a
      radial-emitting fiber. Different powers and pullback speeds were used to achieve
      fluences of 30, 60, and 90 J/cm. For segmental RFA, 1 cycle of 20 s was analyzed.
      EVSA was performed with two and three pulses of steam per centimeter. Maximum
      temperature increase, time span of relevant temperature increase, and area under
      the curve of the time of relevant temperature increase were measured. In all EVLA
      settings, temperatures increased and decreased rapidly. High fluence is
      associated with significantly higher temperatures and increased time span of
      temperature rise. Temperature profiles of 980- and 1,470-nm EVLA with tulip-tip
      fibers did not differ significantly. Radial EVLA showed significantly higher
      maximum temperatures than tulip-tip EVLA. EVSA resulted in mild peak temperatures
      for longer durations than EVLA. Maximum temperatures with three pulses per
      centimeter were significantly higher than with two pulses. RFA temperature rises
      were relatively mild, resulting in a plateau-shaped temperature profile, similar
      to EVSA. Temperature increase during EVLA is fast with a high-peak temperature
      for a short time, where EVSA and RFA have longer plateau phases and lower maximum
      temperatures. 

PMID- 24292198
TI  - Comments on "Comparison of the influence of ozone and laser therapies on pain,
      swelling, and trismus following impacted third-molar surgery".

PMID- 24292199
TI  - Melasma and low-energy Q-switched laser: treatment assessment by means of in vivo
      confocal microscopy.
AB  - Melasma is an acquired disorder of pigmentation for which several therapeutical
      options are currently available. Among them, low-energy Q-switched Nd:YAG laser
      (1,064 nm) has been successfully applied in case series although its long-term
      efficacy has yet to be proven. In vivo confocal microscopy is a novel imaging
      technique that permits to explore the skin tissue at a nearly histologic
      resolution. The aim of our study was to evaluate the laser treatment efficacy by
      means of confocal microscopy at different time points to elucidate the mechanism
      of action of the laser and its possible drawbacks. Eight women who presented with
      melasma on the face were subjected to low-energy Q-switched Nd:YAG laser
      treatment and then analyzed by means of confocal microscopy. An overall
      improvement of melasma was noticed clinically and microscopically by means of
      confocal microscopy. Four cases revealed the presence of dendritic-shaped cells
      upon confocal microscopy and those patients were the ones presenting with a
      relapse of the disease. The interpretation of these cells is that they could
      represent reasonably activated melanocytes. This opens the question whether laser
      treatment should be modulated to avoid side-effects associated with its use.
      Confocal microscopy has emerged as an excellent tool for a better understanding
      of the changes occurring during laser treatment.

PMID- 24292200
TI  - A new long-term care facilities model in nova scotia, Canada: protocol for a
      mixed methods study of care by design.
AB  - BACKGROUND: Prior to the implementation of a new model of care in long-term care
      facilities in the Capital District Health Authority, Halifax, Nova Scotia,
      residents entering long-term care were responsible for finding their own family
      physician. As a result, care was provided by many family physicians responsible
      for a few residents leading to care coordination and continuity challenges. In
      2009, Capital District Health Authority (CDHA) implemented a new model of long
      term care called "Care by Design" which includes: a dedicated family physician
      per floor, 24/7 on-call physician coverage, implementation of a standardized
      geriatric assessment tool, and an interdisciplinary team approach to care. In
      addition, a new Emergency Health Services program was implemented shortly after,
      in which specially trained paramedics dedicated to long-term care responses are
      able to address urgent care needs. These changes were implemented to improve
      primary and emergency care for vulnerable residents. Here we describe a
      comprehensive mixed methods research study designed to assess the impact of these
      programs on care delivery and resident outcomes. The results of this research
      will be important to guide primary care policy for long-term care. OBJECTIVE: We
      aim to evaluate the impact of introducing a new model of a dedicated primary care
      physician and team approach to long-term care facilities in the CDHA using a
      mixed methods approach. As a mixed methods study, the quantitative and
      qualitative data findings will inform each other. Quantitatively we will measure
      a number of indicators of care in CDHA long-term care facilities pre and post
      implementation of the new model. In the qualitative phase of the study we will
      explore the experience under the new model from the perspectives of stakeholders
      including family doctors, nurses, administration and staff as well as residents
      and family members. The proposed mixed method study seeks to evaluate and make
      policy recommendations related to primary care in long-term care facilities with
      a focus on end-of-life care and dementia. METHODS: This is a mixed methods study
      with concurrent quantitative and qualitative phases. In the quantitative phase, a
      retrospective time series study is being conducted. Planned analyses will measure
      indicators of clinical, system, and health outcomes across three time periods and
      assess the effect of Care by Design as a whole and its component parts. The
      qualitative methods explore the experiences of stakeholders (ie, physicians,
      nurses, paramedics, care assistants, administrators, residents, and family
      members) through focus groups and in depth individual interviews. RESULTS: Data
      collection will be completed in fall 2013. CONCLUSIONS: This study will generate
      a considerable amount of outcome data with applications for care providers,
      health care systems, and applications for program evaluation and quality
      improvement. Using the mixed methods design, this study will provide important
      results for stakeholders, as well as other health systems considering similar
      programs. In addition, this study will advance methods used to research new
      multifaceted interdisciplinary health delivery models using multiple and varied
      data sources and contribute to the discussion on evidence based health policy and
      program development.

PMID- 24292201
TI  - Enhancement of bioelectricity generation by manipulation of the electron shuttles
      synthesis pathway in microbial fuel cells.
AB  - Microbial fuel cells (MFCs) are promising for generating bioenergy and treating
      organic waste simultaneously. However, low extracellular electron transfer (EET)
      efficiency between electrogens and anodes remains one of the major bottlenecks in
      practical applications of MFCs. In this paper, pyocyanin (PYO) synthesis pathway
      was manipulated to improve the EET efficiency in Pseudomonas aeruginosa
      inoculated MFCs. By overexpression of phzM (methyltransferase encoding gene), the
      maximum power density of P. aeruginosa-phzM-inoculated MFC was enhanced to 166.68
      MUW/cm(2), which was four folds of the original strain. In addition, the phzM
      overexpression strain exhibited an increase of 1.6 folds in PYO production and
      about a onefold decrease in the total internal resistance than the original
      strain, which should underlie the enhancement of the EET efficiency and the
      electricity power output (EPT). On the basis of these results, the manipulation
      of electron shuttles synthesis pathways could be an efficient approach to improve
      the EPT of MFCs.

PMID- 24292202
TI  - Carbon dioxide sequestration from industrial flue gas by Chlorella sorokiniana.
AB  - The present study investigated the feasibility of using Chlorella sorokiniana for
      CO2 sequestration from industrial flue gas. The flue gas emitted from the oil
      producing industry contains mostly CO2 and H2S (15.6% (v/v) and 120 mg L(-1),
      respectively) along with nitrogen, methane, and other hydrocarbons. The high
      concentration of CO2 and H2S had an inhibitory effect on the growth of C.
      sorokiniana. Some efforts were made for the maximization of the algal biomass
      production using different techniques such as diluted flue gas, flue gas after
      passing through the scrubber, flue gas passing through serially connected
      photobioreactors and two different reactors. The highest reduction in the CO2
      content of inlet flue gas was 4.1% (v/v). Some new pigments were observed in the
      flue gas sequestered biomass. Fatty acid composition in the total lipid was
      determined to evaluate its suitability for food, feed, and biofuel.

PMID- 24292203
TI  - The relationship of oxygen uptake rate and k(L)a with rheological properties in
      high cell density cultivation of docosahexaenoic acid by Schizochytrium sp. S31.
AB  - Three independent cultures by fed batch strategy under different oxygen supply
      levels were investigated with Schizochytrium sp. S31 on glycerol in 50 L
      bioreactor. Three cultures all achieved high cell density cultivation (HCDC) with
      more than 100 g/L biomass density. However, the culture with middle oxygen supply
      level achieved the highest DHA concentration at 21.26 g/L. Dissolved oxygen (DO)
      limitation was commonly encountered in the present cultures, which was due to the
      dramatic decrease of kLa in high oxygen supply culture resulted from
      significantly increasing apparent viscosity of the broth. The rheological
      properties of the three cultures all exhibited shear-thinning behavior. The
      oxygen uptake rate (OUR) predominately influenced by kLa was suggested to replace
      DO as on-line control parameter for scale-up production of DHA.

PMID- 24292204
TI  - Effect of phosphorus on biodiesel production from Scenedesmus obliquus under
      nitrogen-deficiency stress.
AB  - In order to study the effect of phosphorus on biodiesel production from
      Scenedesmus obliquus especially under nitrogen deficiency conditions, six types
      of media with combinations of nitrogen repletion/depletion and phosphorus
      repletion/limitation/depletion were investigated in this study. It was found that
      nitrogen starvation compared to nitrogen repletion enhanced biodiesel
      productivity. Moreover, biodiesel productivity was further strengthened by
      varying the supply level of phosphorus from depletion, limitation, through to
      repletion. The maximum FAMEs productivity of 24.2 mg/L/day was obtained in
      nitrogen depletion with phosphorus repletion, which was two times higher than
      that in nutrient complete medium. More phosphorus was accumulated in cells under
      the nitrogen starvation with sufficient phosphorus condition, but no
      polyphosphate was formed. This study indicated that nitrogen starvation plus
      sufficient P supply might be the real "lipid trigger". Furthermore, results of
      the current study suggest a potential application for utilizing microalgae to
      combine phosphorus removal from wastewater with biodiesel production.

PMID- 24292205
TI  - A pumilio homolog in Polycelis sp.
AB  - Pumilio proteins (PUMs), members of the pumilio/fem-3 mRNA-binding factor (PUF)
      family, are eukaryote-specific RNA-binding proteins. We isolated a 2,048-basepair
      cDNA fragment of a pumilio homolog from the planarian flatworm Polycelis sp. This
      pumilio protein (PyPUM) contains a conserved pumilio homology domain (PUM-HD)
      consisting of eight repeats and two flanking half repeats. PyPUM shows high
      similarity to Dugesia japonica pumilio (DjPUM) from another planarian D.
      japonica, and their PUM-HD also shows high similarity to each other. Furthermore,
      our data showed that there is a flatworm-specific spacer between repeats 7 and 8.
      Phylogenetic analysis showed that PyPUM has a closer relationship to other PUM
      homologs from flatworms. These results provide a foundation for future functional
      studies of pumilio gene in Polycelis sp. 

PMID- 24292206
TI  - Chronic metformin treatment is associated with reduced myocardial infarct size in
      diabetic patients with ST-segment elevation myocardial infarction.
AB  - PURPOSE: Increased myocardial infarct (MI) size is associated with higher risk of
      developing left ventricular dysfunction, heart failure and mortality.
      Experimental studies have suggested that metformin treatment reduces MI size
      after induced ischaemia but human data is lacking. We aimed to investigate the
      effect of metformin on MI size in patients presenting with an acute MI. METHODS:
      All consecutive patients (n = 3,288) presenting to our hospital with ST-segment
      elevation myocardial infarction (STEMI) undergoing primary PCI between January
      2004 and December 2010 were included in this retrospective analysis. Patients
      with diabetes were divided according to metformin versus non-metformin based
      pharmacotherapy. MI size was estimated using peak values of serum creatine kinase
      (CK), myocardial band of CK (CK-MB), and troponin-T. RESULTS: We identified 677
      (20.6 %) patients with diabetes, of whom 189 (27.9 %) were treated with
      metformin. Chronic metformin treatment was associated with lower peak levels of
      CK (1,101 vs. 1,422 U/L, P = 0.005), CK-MB (152 vs. 182 U/L, P = 0.018) and
      troponin-T (2.5 vs. 4.0 ng/L, P = 0.021) compared to non-metformin using
      diabetics. After adjustment for age, sex, TIMI flow post PCI, and previous MI,
      the use of metformin treatment remained an independent predictor of smaller MI
      size. Patient with diabetes treated with metformin had even smaller MI size than
      patients without diabetes. CONCLUSIONS: Chronic metformin treatment is associated
      with reduced MI size compared to non-metformin based strategies in diabetic
      patients presenting with STEMI. Metformin might have additional beneficial
      effects beyond glucose lowering efficacy.

PMID- 24292208
TI  - A new approach to time-dependent transport through an interacting quantum dot
      within the Keldysh formalism.
AB  - The time-dependent transport through a nanoscale device consisting of a single
      spin-degenerate orbital with on-site Coulomb interaction, coupled to two leads,
      is investigated. Various gate and bias voltage time dependences are considered.
      The key and new point lies in the proposed way to avoid the difficulties of the
      usual heavy computation when dealing with two-time Green's functions within the
      Keldysh formalism. The time-dependent retarded dot Green's functions are
      evaluated, in an efficient manner within a non-canonical Hubbard I approximation.
      Calculations of the time-dependent current are then presented in the wide-band
      limit for different parameter sets. A comparison between the method and the
      Hartree-Fock approximation is performed as well. It is shown that the latter
      cannot account reliably for dynamical aspects of transport phenomena. 

PMID- 24292207
TI  - Diosgenin-induced cognitive enhancement in normal mice is mediated by 1,25D3
      MARRS.
AB  - We previously reported that diosgenin, a plant-derived steroidal sapogenin,
      improved memory and reduced axonal degeneration in an Alzheimer's disease mouse
      model. Diosgenin directly activated the membrane-associated rapid response
      steroid-binding receptor (1,25D3-MARRS) in neurons. However, 1,25D3-MARRS
      mediated diosgenin signaling was only shown in vitro in the previous study. Here,
      we aimed to obtain in vivo evidence showing that diosgenin signaling is mediated
      by 1,25D3-MARRS in the mouse brain. Diosgenin treatment in normal mice enhanced
      object recognition memory and spike firing and cross-correlation in the medial
      prefrontal cortex and hippocampal CA1. In diosgenin-treated mice, axonal density
      and c-Fos expression was increased in the medial prefrontal and perirhinal
      cortices, suggesting that neuronal network activation may be enhanced. The
      diosgenin-induced memory enhancement and axonal growth were completely inhibited
      by co-treatment with a neutralizing antibody for 1,25D3-MARRS. Our in vivo data
      indicate that diosgenin is a memory-enhancing drug and that enhancement by
      diosgenin is mediated by 1,25D3-MARRS-triggered axonal growth.

PMID- 24292209
TI  - Combined physical and chemical nonequilibrium transport model for solution
      conduits.
AB  - Solute transport in karst aquifers is primarily constrained to relatively complex
      and inaccessible solution conduits where transport is often rapid, turbulent, and
      at times constrictive. Breakthrough curves generated from tracer tests in
      solution conduits are typically positively-skewed with long tails evident.
      Physical nonequilibrium models to fit breakthrough curves for tracer tests in
      solution conduits are now routinely employed. Chemical nonequilibrium processes
      are likely important interactions, however. In addition to partitioning between
      different flow domains, there may also be equilibrium and nonequilibrium
      partitioning between the aqueous and solid phases. A combined physical and
      chemical nonequilibrium (PCNE) model was developed for an instantaneous release
      similar to that developed by Leij and Bradford (2009) for a pulse release. The
      PCNE model allows for partitioning open space in solution conduits into mobile
      and immobile flow regions with first-order mass transfer between the two regions
      to represent physical nonequilibrium in the conduit. Partitioning between the
      aqueous and solid phases proceeds either as an equilibrium process or as a first
      order process and represents chemical nonequilibrium for both the mobile and
      immobile regions. Application of the model to three example breakthrough curves
      demonstrates the applicability of the combined physical and chemical
      nonequilibrium model to tracer tests conducted in karst aquifers, with
      exceptionally good model fits to the data. The three models, each from a
      different state in the United States, exhibit very different velocities,
      dispersions, and other transport properties with most of the transport occurring
      via the fraction of mobile water. Fitting the model suggests the potentially
      important interaction of physical and chemical nonequilibrium processes. 

PMID- 24292210
TI  - Sociality and oxytocin and vasopressin in the brain of male and female dominant
      and subordinate mandarin voles.
AB  - The dominant-subordinate hierarchy in animals often needs to be established via
      agonistic encounters and consequently affects reproduction and survival.
      Differences in brain neuropeptides and sociality among dominant and subordinate
      males and females remain poorly understood. Here we explore neuropeptide levels
      and sociality during agonistic encounter tests in mandarin voles. We found that
      dominant mandarin voles engaged in higher levels of approaching, investigating,
      self-grooming and exploring behavior than subordinates. Dominant males habituated
      better to a stimulus vole than dominant females. Dominant males displayed
      significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei
      and more vasopressin-immunoreactive neurons in the paraventricular nuclei,
      supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates.
      Dominant females displayed significantly more vasopressin-immunoreactive neurons
      in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex
      differences were found in the level of oxytocin and vasopressin. These results
      indicate that distinct parameters related to central nervous oxytocin and
      vasopressin are associated with behaviors during agonistic encounters in a sex
      specific manner in mandarin voles. 

PMID- 24292211
TI  - Initial clinical results of simultaneous 18F-FDG PET/MRI in comparison to 18F-FDG
      PET/CT in patients with head and neck cancer.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic capability of
      simultaneous (18)F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/MRI compared to (18)F-FDG PET/CT as well as their single components in head
      and neck cancer patients. METHODS: In a prospective study 17 patients underwent
      (18)F-FDG PET/CT for staging or follow-up and an additional (18)F-FDG PET/MRI
      scan with whole-body imaging and dedicated examination of the neck. MRI, CT and
      PET images as well as PET/MRI and PET/CT examinations were evaluated
      independently and in a blinded fashion by two reader groups. Results were
      compared with the reference standard (final diagnosis determined in consensus
      using all available data including histology and follow-up). Sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      were calculated. RESULTS: A total of 23 malignant tumours were found with the
      reference standard. PET/CT showed a sensitivity of 82.7%, a specificity of 87.3%,
      a PPV of 73.2% and a NPV of 92.4%. Corresponding values for PET/MRI were 80.5,
      88.2, 75.6 and 92.5%. No statistically significant difference in diagnostic
      capability could be found between PET/CT and PET/MRI. Evaluation of the PET part
      from PET/CT revealed highest sensitivity of 95.7%, and MRI showed best
      specificity of 96.4%. There was a high inter-rater agreement in all modalities
      (Cohen's kappa 0.61-0.82). CONCLUSION: PET/MRI of patients with head and neck
      cancer yielded good diagnostic capability, similar to PET/CT. Further studies on
      larger cohorts to prove these first results seem justified.

PMID- 24292213
TI  - Long-term results of the transattical approach: an alternative technique for
      cochlear implantation.
AB  - Cochlear implantation through the standard posterior tympanotomy approach may
      sometimes be challenging. In cases with complicated anatomy or malformations, an
      alternative surgical technique may be chosen. The transattical approach is a
      simple technique based on a mastoidectomy and a transmeatal cochleostomy. The
      electrode is driven to the middle ear through the attic. This way it overcomes
      some of the standard technique's drawbacks. Our aim is to assess the value of
      this alternative approach in cochlear implant surgery. We conducted a comparative
      retrospective study; we included 74 patients operated by transattical approach
      and 59 patients operated with the standard technique. Auditory performance and
      complications at long term follow-up were compared. The consequences of the
      different trajectory of the electrode in the transattical approach were also
      studied. No significant differences were found between both groups regarding
      complication rates and cochlear implant performance. The electrode's integrity
      was not significantly affected by its different position and angles, when
      compared to the standard approach. We conclude that transattical approach is a
      safe technique for cochlear implantation. It may be considered as an alternative
      to the posterior tympanotomy approach for those cases where this cannot be
      performed.

PMID- 24292212
TI  - Modification of the association between obesity and lethal prostate cancer by
      TMPRSS2:ERG.
AB  - BACKGROUND: TMPRSS2:ERG is a hormonally regulated gene fusion present in about
      half of prostate tumors. We investigated whether obesity, which deregulates
      several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer
      outcomes. METHODS: The study included 1243 participants in the prospective
      Physicians' Health Study and Health Professionals Follow-Up Study diagnosed with
      prostate cancer between 1982 and 2005. ERG overexpression (a TMPRSS2:ERG marker)
      was assessed by immunohistochemistry of tumor tissue from radical prostatectomy
      or transurethral resection of the prostate. Body mass index (BMI) and waist
      circumference, measured on average 1.3 years and 5.3 years before diagnosis,
      respectively, were available from questionnaires. Data on BMI at baseline was
      also available. We used Cox regression to calculate hazard ratios and 95%
      confidence intervals (CIs). All statistical tests were two-sided. RESULTS: During
      a mean follow-up of 12.8 years, 119 men developed lethal disease (distant
      metastases or prostate cancer death). Among men with ERG-positive tumors, the
      multivariable hazard ratio for lethal prostate cancer was 1.48 (95% CI = 0.98 to
      2.23) per 5-unit increase in BMI before diagnosis, 2.51 (95% CI = 1.26 to 4.99)
      per 8-inch increase in waist circumference before diagnosis, and 2.22 (95% CI =
      1.35 to 3.63) per 5-unit increase in BMI at baseline. The corresponding hazard
      ratios among men with ERG-negative tumors were 1.10 (95% CI = 0.76 to1.59; P
      interaction = .24), 1.14 (95% CI = 0.62 to 2.10; P interaction = .09), and 0.78
      (95% CI = 0.52 to 1.19; P interaction = .001). CONCLUSIONS: These results suggest
      that obesity is linked with poorer prostate cancer prognosis primarily in men
      with tumors harboring the gene fusion TMPRSS2:ERG.

PMID- 24292214
TI  - Idiopathic latent vestibulopathy: a clinical entity as a cause of chronic
      postural instability.
AB  - The objective of this study is to describe a new clinical entity of idiopathic
      latent vestibulopathy (ILV), in which patients have unilateral or bilateral
      vestibulopathy combined with unsteadiness but without episodic vertigo, auditory
      disturbance, or a medical history suggesting the presence of vestibulopathy. A
      retrospective study of 1,233 consecutive new outpatients was conducted. Two
      legged stance tasks were performed by 11 patients identified as having ILV in
      four conditions: eyes open with and without foam rubber, and eyes closed with and
      without foam rubber. We examined six parameters: the velocity of movement of the
      center of pressure (COP) with eyes closed/foam rubber, the envelopment area
      traced by the movement of the COP with eyes closed/foam rubber, Romberg's ratio
      of velocity and area with foam rubber, and the foam ratios of velocity and area
      with eyes closed. Multiple regression analyses were performed in order to explore
      the relationship between the presence of ILV and the six parameters recorded
      during foam posturography, while adjusting for the subjects' gender and age. The
      presence of ILV had a significantly positive relationship with the values of 4 of
      the 6 parameters. Even though six patients showed only unilateral vestibulopathy,
      their median value in all 6 parameters was greater than that of healthy controls.
      ILV could be a clinical entity accountable for postural instability. 

PMID- 24292215
TI  - Head tilt is pronounced after an ipsilateral head roll in patients with
      vestibular schwannoma.
AB  - The study aimed to measure utricular function by directly quantifying head tilt
      in vestibular schwannoma (VS) patients using regular video-oculography (VOG)
      equipment with integrated head-position sensor, and to correlate the results with
      patients' symptoms and signs. We recorded head tilting after exclusion of visual
      cues (static head tilt), and after returning to the centre following lateral head
      rolls towards each side [subjective head vertical (SHV)]. Head tilt in 43
      patients was measured preoperatively and approximately 4 months postoperatively,
      and compared to that of 20 healthy subjects. Symptoms were assessed with a
      structured questionnaire. Static head tilt in patients was significantly greater
      than in controls (1.0 degrees  +/- 0.9 degrees ) preoperatively (1.6 degrees  +/-
      1.5 degrees , p = 0.04) and postoperatively (1.7 degrees  +/- 1.5 degrees , p =
      0.01). Mean SHV in patients was significantly greater than in controls (1.2
      degrees  +/- 1.0 degrees ) preoperatively (2.0 degrees  +/- 1.9 degrees , p =
      0.03) and postoperatively (2.5 degrees  +/- 1.8 degrees , p = 0.001), increasing
      non-significantly after surgery (p = 0.3). Side-specific SHV after ipsilateral
      head rolls was significantly greater than after contralateral head rolls
      preoperatively (2.8 degrees  +/- 3.3 degrees  vs. -0.5 degrees  +/- 3.0 degrees ,
      p = 0.001) and postoperatively (3.3 degrees  +/- 3.0 degrees  vs. 0.6 degrees  +/
      3.2 degrees , p < 0.001). The intensity of dizziness increased postoperatively
      (p = 0.04), but its effect on quality of life remained unchanged. In conclusion,
      commercial VOG equipment including a head-position sensor allows direct
      evaluation of head tilt in VS patients. The slight head tilt towards the
      ipsilateral side becomes most evident after returning from an ipsilateral head
      roll. 

PMID- 24292216
TI  - Endoscope-assisted second branchial cleft cyst resection via an incision along
      skin line on lateral neck.
AB  - The aim of the study is to report the feasibility of endoscope-assisted second
      branchial cleft cyst resection via a small incision along the skin line on the
      lateral neck. In total, 41 patients from the Department of Otolaryngology, Foshan
      Hospital of Yat-sen University were randomly assigned to conventional (20
      patients) or endoscope-assisted (21 patients) second branchial cleft cyst
      resection. The patient clinical characteristics, operation time, operative
      bleeding volume, postoperative complications, and subjective satisfaction with
      the incision scar (measured using a visual analog scale) were compared between
      the groups. All 41 s branchial cleft cyst resections were successfully performed,
      and the wounds healed uneventfully. The bleeding volume (6.3 +/- 2.5 ml) and
      incision length (2.7 +/- 0.3 cm) differed between the groups (P < 0.00). The mean
      patient satisfaction score was 8.0 +/- 0.8 in the endoscope-assisted surgery
      group and 6.4 +/- 0.9 in the control group (P < 0.00). All of the patients in the
      endoscope-assisted surgery group were satisfied with their cosmetic results. No
      marginal nerve palsy occurred. No complications such as bleeding, salivary
      fistula, or paresis of the marginal mandibular branch occurred. All of the
      patients were disease free through a follow-up period of 6-24 months (median: 14
      months). Endoscope-assisted second branchial cleft cyst resection via a small
      incision along the dermatoglyph on the lateral neck is a feasible technique. This
      procedure may serve as an alternative approach, allowing a minimally invasive
      incision and better cosmetic results.

PMID- 24292217
TI  - Inhibition of tumour cell growth by carnosine: some possible mechanisms.
AB  - The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been
      shown to inhibit, selectively, growth of transformed cells mediated, at least in
      part, by depleting glycolytic ATP levels. The mechanism(s) responsible has/have
      yet to be determined. Here, we discuss a number of probable and/or possible
      processes which could, theoretically, suppress glycolytic activity which would
      decrease ATP supply and generation of metabolic intermediates required for
      continued cell reproduction. Possibilities include effects on (i) glycolytic
      enzymes, (ii) metabolic regulatory activities, (iii) redox biology, (iv) protein
      glycation, (v) glyoxalase activity, (vi) apoptosis, (vii) gene expression and
      (viii) metastasis. It is possible, by acting at various sites that this
      pluripotent dipeptide may be an example of an endogenous "smart drug". 

PMID- 24292218
TI  - Necklace-like mesoporous MgO/TiO2 heterojunction structures with excellent
      capability for water treatment.
AB  - Necklace-like MgO/TiO2 heterojunction structures were synthesized by a simple and
      economical precursor calcination method for the first time. The obtained unique
      MgO/TiO2 heterojunction structures exhibit an excellent removal performance
      towards toxic As(v) ions combined with good photocatalytic properties towards
      organic dyes. 

PMID- 24292220
TI  - Phantom limb pain exacerbated by intravenous ketamine.

PMID- 24292219
TI  - Difficult airway in an infant with fetal valproate syndrome.

PMID- 24292221
TI  - [Total laryngopharyngectomy and reconstruction with a jejunum speech siphon : A
      case report].
AB  - Advanced laryngeal and hypopharyngeal carcinomas are associated with a poor
      prognosis and a pronounced loss of quality of life due to impairment of the
      swallowing and voice function. The fundamental therapeutic challenge is
      successful tumor control with concomitant rehabilitation of swallowing and voice
      functions. Further objectives are a low complications rate (fistula, aspiration)
      and prompt transfer to the adjuvant radio-oncologic therapy. With these factors
      in mind, the microvascular anastomosed jejunum speech siphon with a biventer rein
      has proven to be an effective method of reconstruction following extensive
      circular laryngopharyngeal resections. In this case report, a typical operative
      and postoperative course is presented, as are the functional results. 

PMID- 24292222
TI  - [Negative pressure pulmonary edema after peritonsillar abscess tonsillectomy].
AB  - We report on a 19-year-old patient who developed negative pressure pulmonary
      edema (NPPE) with respiratory insufficiency following abscess tonsillectomy. NPPE
      is an unpredictable and life-threatening postoperative complication characterized
      by respiratory insufficiency. It may arise immediately after extubation or later
      in the postoperative period. NPPE is frequently observed after laryngospasm or in
      combination with space-occupying lesions in the pharynx and larynx. Treatment
      comprises the immediate correction of hypoxemia, preferably by noninvasive
      respiratory support using continuous positive airway pressure (CPAP), although in
      some cases reintubation is necessary. 

PMID- 24292223
TI  - [Peripheral facial nerve palsy caused by a tumor in the epitympanum].

PMID- 24292224
TI  - [Differential diagnosis of chronic maxillary sinusitis].

PMID- 24292226
TI  - Binge drinking and the differential influence of ethanol on cognitive control
      subprocesses: a novel field of neurotoxicology.

PMID- 24292225
TI  - Differential gene expression in human hepatocyte cell lines exposed to the
      antiretroviral agent zidovudine.
AB  - Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the most widely used nucleoside
      reverse transcriptase inhibitor for the treatment of AIDS patients and prevention
      of mother-to-child transmission of HIV-1. Previously, we demonstrated that AZT
      had significantly greater growth inhibitory effects upon the human liver
      carcinoma cell line HepG2 as compared to the immortalized human liver cell line
      THLE2. We have now used gene expression profiling to determine the molecular
      pathways associated with toxicity in both cell lines. HepG2 cells were incubated
      with 0, 2, 20, or 100 MUM AZT for 2 weeks; THLE2 cells were treated with 0, 50,
      500, or 2,500 MUM AZT, concentrations that were equi-toxic to those used in the
      HepG2 cells. After the treatment, total RNA was isolated and subjected to
      microarray analysis. Global analysis of gene expression, with a false discovery
      rate <=0.01 and a fold change >=1.5, indicated that 6- to 70-fold more genes were
      differentially expressed in a significant concentration-dependent manner in HepG2
      cells when compared to THLE2 cells. Comparative analysis indicated that 7 % of
      these genes were common to both cell lines. Among the common differentially
      expressed genes, 70 % changed in the same direction, most of which were
      associated with cell death and survival, cell cycle, cell growth and
      proliferation, and DNA replication, recombination, and repair. As determined by
      the uptake of [methyl-(3)H]AZT, the intracellular levels of total AZT were
      approximately twofold higher in THLE2 cells than in HepG2 cells. The expression
      of thymidine kinase 1 (TK1) and UDP-glucuronosyltransferase 2B7 (UGT2B7) genes
      that regulate the metabolic activation and deactivation of AZT, respectively, was
      increased in HepG2 cells but decreased in THLE2 cells after treatment with AZT.
      This differential response in AZT metabolism was confirmed by real-time PCR,
      western blotting, and/or enzymatic assays. These data indicate that molecular
      pathways involved with cell death and survival, cell cycle, cell growth and
      proliferation, and DNA replication, recombination, and repair are involved in the
      toxicities associated with AZT in both human cell lines, and that the difference
      in expression of TK1 and UGT2B7 in response to AZT treatment in HepG2 cells and
      THLE2 cells might explain why HepG2 cells are more sensitive than THLE2 cells to
      the toxicity of AZT.

PMID- 24292227
TI  - Response to Letter of Ralph J Cicerone and Kevin Crowley regarding "How the US
      National Academy of Sciences misled the world community on cancer risk
      assessment: new findings challenge historical foundations of the linear dose
      response." [DOI 10.1007/s00204-013-1105-6, Review Article].

PMID- 24292228
TI  - Neurological complications in infective endocarditis.

PMID- 24292229
TI  - Prognostic impact of RING box protein-1 (RBX1) expression in gastric cancer.
AB  - BACKGROUND: RING box protein-1 (RBX1) is an essential component of the E3
      ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered
      expression of RBX1 has been reported in several human cancers, the role of RBX1
      in gastric cancer remains unknown. METHODS: We investigated the RBX1 expression
      in primary gastric cancer tissues from 145 patients by immunohistochemistry, and
      explored its clinical relevance and prognostic value. Furthermore, the effect of
      RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA
      silencing technique. RESULTS: The RBX1 expression was abundant in gastric cancer
      tissues. There was a significant difference in the expression level of RBX1 in
      terms of the tumor depth (P = 0.008), presence of distant metastasis (P = 0.016)
      and venous invasion (P = 0.005). The postoperative overall (P < 0.001) and
      relapse-free survival (P < 0.001) rates were significantly poorer in patients
      with RBX1-high tumors than in patients with RBX1-low tumors. There was a
      significant correlation of the RBX1 status with postoperative hematogenous
      recurrence (P = 0.013). Importantly, the RBX1 status was identified as an
      independent prognostic factor for gastric cancer (P = 0.002). Furthermore, RBX1
      gene silencing significantly inhibited the proliferation of gastric cancer cells
      in vitro. CONCLUSIONS: The RBX1 expression has a significant prognostic value in
      gastric cancer. RBX1 might play an important role in regulating the proliferation
      of gastric cancer cells and promoting the development of postoperative
      recurrence. Our data provide a rationale for developing a novel therapy targeting
      RBX1 for gastric cancer.

PMID- 24292230
TI  - Value predispositions as perceptual filters: Comparing of public attitudes toward
      nanotechnology in the United States and Singapore.
AB  - This study compares public attitudes toward nanotechnology in the United States
      and Singapore, using large-scale survey data in both countries. Results indicate
      that Singaporeans tend to be more knowledgeable about and familiar with
      nanotechnology than the U.S. public. Singaporeans tend to perceive greater
      benefits and fewer potential risks of nanotechnology, and to indicate greater
      support for government funding for nanotechnology than the U.S. public. Between
      the two countries, perceived familiarity with nanotechnology and the benefits and
      risks of the emerging technology tend to be interpreted differently through the
      lens of value predispositions (religiosity and deference to scientific authority)
      and therefore they indirectly affect public support. Specifically, the U.S.
      public tends to use religiosity to interpret benefits and Singaporeans are
      inclined to use religiosity to think about risks. Deference to scientific
      authority also moderates the impact of perceived familiarity with nanotechnology
      on funding support for the technology among the U.S. public. 

PMID- 24292231
TI  - Nacherzeugung, Nachverstehen: A phenomenological perspective on how public
      understanding of science changes by engaging with online media.
AB  - It is widely acknowledged in science education that everyday understandings and
      evidence are generally inconsistent with the scientific view of the matter:
      "heartache" has little to do with matters cardiopulmonary, and a rising or
      setting sun actually reflects the movements of the earth. How then does a member
      of the general public, which in many areas of science is characterized as
      "illiterate" and "non-scientific," come to regard something scientifically?
      Moreover, how do traditional unscientific (e.g., Ptolemaic) views continue their
      lives, even many centuries after scientists have overthrown them in what are
      termed scientific (e.g., Copernican) revolutions? In this study, we develop a
      phenomenological perspective, using Edmund Husserl's categories of Nacherzeugung
      and Nachverstehen, which provide descriptive explanations for our observations.
      These observations are contextualized in a case study using online video and
      historical materials concerning the motions of the heart and blood to exemplify
      our explanations.

PMID- 24292232
TI  - Parental olfactory experience influences behavior and neural structure in
      subsequent generations.
AB  - Using olfactory molecular specificity, we examined the inheritance of parental
      traumatic exposure, a phenomenon that has been frequently observed, but not
      understood. We subjected F0 mice to odor fear conditioning before conception and
      found that subsequently conceived F1 and F2 generations had an increased
      behavioral sensitivity to the F0-conditioned odor, but not to other odors. When
      an odor (acetophenone) that activates a known odorant receptor (Olfr151) was used
      to condition F0 mice, the behavioral sensitivity of the F1 and F2 generations to
      acetophenone was complemented by an enhanced neuroanatomical representation of
      the Olfr151 pathway. Bisulfite sequencing of sperm DNA from conditioned F0 males
      and F1 naive offspring revealed CpG hypomethylation in the Olfr151 gene. In
      addition, in vitro fertilization, F2 inheritance and cross-fostering revealed
      that these transgenerational effects are inherited via parental gametes. Our
      findings provide a framework for addressing how environmental information may be
      inherited transgenerationally at behavioral, neuroanatomical and epigenetic
      levels. 

PMID- 24292234
TI  - Necrotizing lymphadenitis (NEL) is a systemic disease characterized by blastic
      transformation of CD8+ cells and apoptosis of CD4+ cells.
AB  - This clinicopathological, immunohistochemical, electron microscopic, and
      serological study of 382 cases (148 male, 234 female) of necrotizing
      lymphadenitis (NEL) in Japan confirms NEL as a self-limited disease with
      characteristic clinical features: high fever (38-40  degrees C), painful cervical
      lymphadenopathy (88.3 %), and leukopenia (under 4,000/mm(3)) without seasonal
      occurrence. Patient age varied from 5 to 80 years, but 62.8 % was younger than 30
      years. There were five recurrent cases and four familial cases. In several cases,
      elevated serum aminotransaminase and antinuclear antibodies were found. Early in
      the disease, peripheral blood CD8+ cells were more abundant than CD4+ cells, but
      CD8+ cells decreased gradually with clinical progression, leading to an
      increasing ratio of CD4+/CD8+ cells during clinical course. Morphological
      features of involved lymph nodes are numerous CD8+ large immunoblasts, smaller
      CD4+ lymphocytes, plasmacytoid dendritic cells, histiocytes, and macrophages, the
      latter with phagocytized CD4+ apoptotic lymphocytes. Granulocytes are generally
      absent. These characteristics suggest that NEL is a reactive disease
      characterized by diploid disrupted CD4+ cells and CD8+ cells transforming to
      blastic cells. The etiology of the disease remains unknown, although viral
      infection is suggested, and its pathogenesis might include autoimmunity. Clinical
      characteristics and cytological and histological findings on lymph node biopsies
      can improve NEL diagnosis.

PMID- 24292235
TI  - Determination of the elastic properties of graphene by indentation and the
      validity of classical models of indentation.
AB  - Ab initio and empirical force field methods are used to simulate the loading of a
      large graphene membrane under an indenter analogous to an atomic force microscope
      tip. From these calculations we attempt to resolve ambiguities around
      determination of the elastic constants of graphene from such indentation
      experiments. We investigate the effect of the formation of wrinkles and more
      importantly the applicability of modelling the membrane as a continuous elastic
      sheet. By comparing empirical potential and large scale density functional theory
      calculations we have also assessed the performance of classical potentials in
      describing bending in this system. We find that the in-plane Young's modulus
      deduced from the indentation simulations using the classical expression for a
      clamped elastic membrane under a central point load is not consistent with that
      calculated directly from the in-plane stress-strain curve. 

PMID- 24292233
TI  - Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development
      and memory.
AB  - Tumor necrosis factor alpha (TNF) is a proinflammatory cytokine with established
      roles in host defense and immune system organogenesis. We studied TNF function
      and found a previously unidentified physiological function that extends its
      effect beyond the host into the developing offspring. A partial or complete
      maternal TNF deficit, specifically in hematopoietic cells, resulted in reduced
      milk levels of the chemokines IP-10, MCP-1, MCP-3, MCP-5 and MIP-1beta, which in
      turn augmented offspring postnatal hippocampal proliferation, leading to improved
      adult spatial memory in mice. These effects were reproduced by the postpartum
      administration of a clinically used anti-TNF agent. Chemokines, fed to suckling
      pups of TNF-deficient mothers, restored both postnatal proliferation and spatial
      memory to normal levels. Our results identify a TNF-dependent 'lactrocrine'
      pathway that programs offspring hippocampal development and memory. The level of
      ambient TNF is known to be downregulated by physical activity, exercise and
      adaptive stress. We propose that the maternal TNF-milk chemokine pathway evolved
      to promote offspring adaptation to post-weaning environmental challenges and
      competition. 

PMID- 24292236
TI  - Fabrication and characterization of flexible and tunable plasmonic
      nanostructures.
AB  - We present a novel method to fabricate flexible and tunable plasmonic
      nanostructures based on combination of soft lithography and nanosphere
      lithography, and perform a comprehensive structural and optical characterization
      of these structures. Spherical latex particles are uniformly deposited on glass
      slides and used as molds for polydimethylsiloxane to obtain nanovoid structures.
      The diameter and depth of the nanostructures are controlled by the size of the
      latex particles. These surfaces are coated with a thin Ag layer for fabrication
      of uniform plasmonic nanostructures. Structural characterization of these
      surfaces is performed by SEM and AFM. Optical properties of these plasmonic
      nanostructures are evaluated via UV/Vis absorption spectroscopy, dark field
      microscopy, and surface-enhanced Raman spectroscopy (SERS). Position of the
      surface plasmon absorption depends on the diameter and depth of the
      nanostructures. SERS enhancement factor (measured up to 1.4 * 106) is dependent
      on the plasmon absorption wavelength and laser wavelength used in these
      experiments.

PMID- 24292237
TI  - Inherent errors of the fixed-frame counting method for corneal endothelial cell
      density in eye banks.
AB  - The aim of this work was to analyze the magnitude of inherent errors associated
      with the fixed-frame counting method for corneal endothelial cell density (ECD)
      measurements. This technique is common among most eye banks worldwide. Three
      types of mosaics were used: regular and irregular tessellated mosaics (eight
      increasing densities ranging from 800 to 3,600 cells/mm(2) by steps of 400
      cells/mm(2)) generated by a computer, and real mosaics (four specimens) obtained
      from human corneal endothelium flat mounted and stained with Alizarin red. On the
      three mosaics, the fixed-frame counting method was applied using a computer
      program. The ECD was calculated for 3,000 successive random positions from
      calibrated grids which area ranged from 50 * 50 to 300 * 300 MUm(2) (incremental
      steps of 25 MUm). For each grid, the ECD was expressed either as a single count,
      a mean of five or a mean of 10 measures. The fixed-frame count was constantly
      associated with an inherent variability but repeatability increased with larger
      grid size and ECD. The mean calculated out of 10 measures was the most reliable,
      but still, we noted +/-5 % of residual variability from the real ECD. The 100 *
      100 MUm(2) grid manual counts, performed in many eye banks, should be abandoned
      and upgraded to at least 200 * 200 MUm(2) grid counts. Digital image analysis
      with a variable frame counting method would be the best alternative.

PMID- 24292238
TI  - Effects of in combination antioxidant supplementation on microscopic and
      oxidative parameters of freeze-thaw bull sperm.
AB  - The present study was conducted to determine the effect of reduced glutathione
      (GSH) and superoxide dismutase (SOD) supplementation in the bull semen freezing
      extender on post-thaw parameters of Holstein and Simmental bull sperm. Semen were
      collected from seven bulls (four Holstein and three Simmental) and cryopreserved
      in the Tris-egg-yolk based extender as control group and supplemented with
      various concentrations of GSH * SOD (5 * 100, 7.5 * 100, 5 * 150, and 7.5 * 150
      mM * IU mL(-1)) in treatment groups. Microscopic parameters were evaluated in
      terms of total motility parameters using computer assisted semen analysis and
      viability and membrane integrity were assessed using Eosin-Nigrosin stains and
      hypo-osmotic swelling test (HOST), respectively after thawing the semen.
      Malonaldialdehyde (MDA) level, SOD and glutathione peroxides (GPx) activities
      were assessed immediately after thawing. Results showed that supplementation of
      the cryopreservation medium with various concentrations of GSH * SOD improved
      total motility (TM) and progressive motility parameters for Holstein (P < 0.05)
      semen, and values of TM and HOST for Simmental semen compared to the control
      group (P < 0.01) after semen thawing. Addition of antioxidant to Holstein semen
      samples decreased the level of MDA and increased GPx activities compared to
      control groups (P < 0.05). SOD activities increased in Simmental bull samples
      compare to the control group (P < 0.01), but not differ in Holstein, while these
      activities. In conclusion, supplementation of antioxidant to the semen extender
      as combination (GSH * SOD) improved the semen post-thaw qualities which may be
      associated with a reduction in lipid peroxidation as well as an increase in the
      antioxidant enzyme activities.

PMID- 24292239
TI  - Older people's experiences of therapeutic exercise as part of a falls prevention
      service: survey findings from England, Wales and Northern Ireland.
AB  - INTRODUCTION: falling, and fear of falling, significantly affect older people and
      their lifestyle resulting in loss of confidence, restriction of activity and
      deteriorating quality of life. Multi-factorial assessment and active
      participation in an evidence-based exercise programme are key interventions to
      prevent and manage falls. OBJECTIVE: to examine older people's experiences of
      therapeutic exercise as part of a falls prevention service in NHS Trusts in
      England, Wales and Northern Ireland. METHODS: a cross-sectional survey targeted
      patients and staff members delivering exercise interventions for reducing falls.
      A multi-disciplinary group including patient and staff representatives developed
      a 20-item patient questionnaire and a 12-item staff questionnaire that were
      distributed to 94 NHS Trusts (113 participating sites within the NHS Trusts) in
      October 2011. RESULTS: response was 57% for the patient sample and 88% for the
      staff sample. The median (IQR) age of patients was 82 (77-86) years. 72% were
      women. Two-thirds reported attending group-based therapeutic exercise classes
      generally of short duration (80% <12 weeks) and low intensity (85% one class per
      week) at hospitals and community venues. Balance and strength exercises were
      prescribed; 68% reported using resistance equipment such as ankle weights and/or
      exercise band. Only 52% reported exercises were made more difficult as they
      improved. However, patient satisfaction levels were high (95% satisfied or very
      satisfied). Patients and staff reported limited availability of strength and
      balance follow-up classes. CONCLUSION: despite high levels of patient
      satisfaction therapeutic exercise provision was limited and implementation of
      evidence-based exercise interventions by healthcare providers is incomplete and
      varies widely. Patients and staff wanted greater availability of long-term
      exercise services for falls prevention.

PMID- 24292241
TI  - Dynamic nanocrystal response and high temperature growth of carbon nanotube
      ferroelectric hybrid nanostructure.
AB  - A long standing problem related to the capping of carbon nanotubes (CNT) by
      inorganic materials at high temperature has been solved. In situ dynamic response
      of Pb(Zr0.52Ti0.48)O3 (PZT) nanocrystals attached to the wings of the outer
      surface of PZT/CNT hybrid-nanostructure has been demonstrated under a constant
      energy high-resolution transmission electron microscopy (HRTEM) e-beam. PZT
      nanocrystals revealed that the crystal orientations, positions, faces, and
      hopping states change with time. HRTEM study has been performed to investigate
      the microstructure of hybrid nanostructures and nanosize polycrystal trapped
      across the wings. Raman spectroscopy was utilized to investigate the local
      structures, defects, crystal qualities and temperature dependent growth and
      degradation of hybrid nanostructures. Raman spectra indicate that MWCNT and
      PZT/MWCNT/n-Si possess good quality of CNT before and after PZT deposition until
      650  degrees C. The monoclinic Cc/Cm phase of PZT which is optimum in
      piezoelectric properties was prominent in the hybrid structure and should be
      useful for device applications. An unusual hexagonal faceting oscillation of the
      nano-crystal perimeter on a 10-30 s period is also observed. 

PMID- 24292240
TI  - Acoustic rhinometry in persons recruited from the general population and
      diagnosed with chronic rhinosinusitis according to EPOS.
AB  - Chronic rhinosinusitis (CRS) is a disease related to the nose and the paranasal
      sinus as defined by the European Position Paper on Rhinosinusitis and Nasal
      Polyps (EPOS) criteria. The criteria include subjective symptoms, such as nasal
      obstruction, and objective findings by endoscopy. Acoustic rhinometry (AR) is an
      objective method to determine nasal cavity geometry. The technique is based on a
      sound pulse reflection analysis in the nasal cavity and determines cross
      sectional areas as a function of distance as well as volume. AR measurements in
      persons recruited from the general population, with and without CRS based on the
      clinical EPOS criteria, were investigated. As part of a trans-European study, 362
      persons, comprising 91 persons with CRS and 271 persons without CRS, were
      examined by an otolaryngologist including rhinoscopy. Minimum cross-sectional
      area, distance to minimum cross-sectional area, and volume in the nasal cavity
      were measured by acoustic rhinometry and all participants underwent Peak Nasal
      Inspiratory Flow (PNIF) and allergy test. A difference in AR was found before and
      after decongestion, but no difference was seen between CRS patients and controls.
      Positive correlation between AR and PNIF was found and AR was capable of
      identifying mucosal oedema and septum deviation visualised by rhinoscopy. In
      conclusion, AR, as a single instrument, was not capable of discriminating persons
      with CRS from persons without CRS in the general population. However, AR
      correlates well with PNIF and was capable of identifying septum deviation and
      mucosal oedema. 

PMID- 24292242
TI  - Sex-specific differences in desiccation resistance and the use of energy
      metabolites as osmolytes in Drosophila melanogaster flies acclimated to
      dehydration stress.
AB  - In the Indian subcontinent, there are significant between-population variations
      in desiccation resistance in Drosophila melanogaster, but the physiological basis
      of adult acclimation responses to ecologically relevant humidity conditions is
      largely unknown. We tested the hypothesis that increased desiccation resistance
      in acclimated flies is associated with changes in cuticular permeability and/or
      content of energy metabolites that act as osmolytes. Under an ecologically
      relevant humidity regime (~50 % relative humidity), both sexes showed desiccation
      acclimation which persisted for 2-3 days. However, only females responded to
      acclimation at ~5 % relative humidity (RH). Acclimated flies exhibited no changes
      in the rate of water loss, which is consistent with a lack of plastic changes in
      cuticular traits (body melanization, epicuticular lipid). Therefore, changes in
      cuticular permeability are unlikely in drought-acclimated adult flies of D.
      melanogaster. In acclimated flies, we found sex differences in changes in the
      content of osmolytes (trehalose in females versus glycogen in males). These sex
      specific changes in osmolytes are rapid and reversible and match to corresponding
      changes in the increased desiccation resistance levels of acclimated flies.
      Further, the increased content of trehalose in females and glycogen in males
      support the bound-water hypothesis for water retention in acclimated flies. Thus,
      drought acclimation in adult flies of D. melanogaster involves inducible changes
      in osmolytes (trehalose and glycogen), while there is little support for changes
      in cuticular permeability.

PMID- 24292243
TI  - A "turn-on" carbon nanotube-Ag nanoclusters fluorescent sensor for sensitive and
      selective detection of Hg2+ with cyclic amplification of exonuclease III
      activity.
AB  - With exonuclease III activity on DNA hybrids containing thymine-Hg(2+)-thymine, a
      label-free ultrasensitive "turn-on" fluorescent sensor involving "quenching" and
      "reappearing" processes based on a carbon nanotube-Ag nanoclusters system is
      demonstrated for amplified determination of Hg(2+). 

PMID- 24292244
TI  - NMR investigations of nitrophorin 2 belt side chain effects on heme orientation
      and seating of native N-terminus NP2 and NP2(D1A).
AB  - Nitrophorin 2 (NP2), one of the four NO-storing and NO-releasing proteins found
      in the saliva of the blood-sucking bug Rhodnius prolixus, has a more ruffled heme
      and a high preference for a particular heme orientation (B) compared with
      nitrophorin 1 and nitrophorin 4, which show not a preference (A to B ratio of
      approximately 1:1), suggesting that it fits more tightly in the beta-barrel
      protein. In this work we have prepared a series of "belt" mutants of NP2(D1A) and
      (DeltaM0)NP2 aimed at reducing the size of aromatic or other residues that
      surround the heme, and investigated them as the high-spin aqua and low-spin N
      methylimidazole complexes. The belt mutants included Y38A, Y38F, F42A, F66A,
      Y85A, Y85F, Y104A, I120T, and a triple mutant of NP2(D1A), the F42L, L106F, I120T
      mutant. Although I120 has been mainly considered to be a distal pocket residue,
      CdeltaH3 of I120 lies directly above the heme 3-methyl, at 2.67 A, of heme
      orientation B, or the 2-vinyl of A, and it thus plays a role as a belt mutant, a
      role that turns out to be extremely important in creating the strong favoring of
      the B heme orientation [A to B ratio of 1:14 for NP2(D1A) or 1:12 for
      (DeltaM0)NP2]. The results show that the 1D (1)H NMR spectra of the high-spin
      forms are quite sensitive to changes in the shape of the heme binding cavity. The
      single mutation I120T eliminates the favorability of the B heme orientation by
      producing a heme A to B orientation ratio of 1:1, whereas the single mutation
      F42A reverses the heme orientation from an A to B ratio of 1:14 seen for NP2(D1A)
      to 10:1 for NP2(D1A,F42A). The most extreme ratio was found for the triple mutant
      of NP2(D1A), NP2(D1A,F42L,L105F,I120T), in which the A to B ratio is
      approximately 25:1, a DeltaG change of about -3.5 kcal/mol or -14.1 kJ/mol with
      respect to NP2(D1A). The seating of the heme is modified as well in that mutant
      and in several others, by rotations of the heme by up to 4 degrees  from the
      seating observed in NP2(D1A), in order to relieve steric interactions between a
      vinyl beta-carbon and a protein side chain, or to fill a cavity created by
      replacing a large protein side chain by a much smaller one; the latter was
      observed for all tyrosine to alanine mutants. These relatively small changes in
      seating have a measurable effect on the NMR spectra of the mutants, but are
      indeed minor in terms of overall seating and reactivity of the NP2(D1A) protein.
      The (1)H NMR resonances of the hemin substituents of the low-spin N
      methylimidazole complexes of NP2(D1A,F42L,L105F,I120T) as well as NP2(D1A,I120T),
      NP2(D1A,Y104A), and NP2(D1A,F42A) have been assigned using natural abundance
      (1)H{(13)C} heteronuclear multiple quantum correlation and (1)H-(1)H nuclear
      Overhauser effect spectroscopy spectra. 

PMID- 24292246
TI  - Imatinib responsiveness in canine mast cell tumors carrying novel mutations of c
      KIT exon 11.
AB  - In 2 individual cases of canine mast cell tumors, we identified 2 novel c-KIT
      mutations in exon 11: a 9-base pair (bp) deletion (c.1663-1671del) and a point
      mutation (c.1676T>A). The 9-bp deletion mutation caused a loss of 3 amino acids,
      corresponding to p.Gln555_Lys557del, and the point mutation resulted in the
      substitution of valine by aspartic acid (p.Val559Asp) in the juxtamembrane domain
      of the protein. Imatinib mesylate, a therapeutic agent for canine mast cell
      tumors, was used to treat both tumors. Complete remission was achieved at 33 and
      14 days after administration, respectively. However, in both cases, the
      therapeutic response subsequently tapered with the duration of remission lasting
      66 and 255 days, respectively. Although these 2 novel c-KIT mutations in exon 11
      were not confirmed to be gain-of-function mutations, a further study may help
      clarify relevance between mutations identified in this report and responsiveness.

PMID- 24292245
TI  - Nickel binding properties of Helicobacter pylori UreF, an accessory protein in
      the nickel-based activation of urease.
AB  - Helicobacter pylori UreF (HpUreF) is involved in the insertion of Ni(2+) in the
      urease active site. The recombinant protein in solution is a dimer characterized
      by an extensive alpha-helical structure and a well-folded tertiary structure.
      HpUreF binds two Ni(2+) ions per dimer, with a micromolar dissociation constant,
      as shown by calorimetry. X-ray absorption spectroscopy indicated that the Ni(2+)
      ions reside in a five-coordinate pyramidal geometry comprising exclusively N/O
      donor ligands derived from the protein, including one or two histidine imidazole
      and carboxylate ligands. Binding of Ni(2+) does not affect the solution
      properties of the protein. Mutation to alanine of His229 and/or Cys231, a pair of
      residues located on the protein surface that interact with H. pylori UreD,
      altered the affinity of the protein for Ni(2+). This result, complemented by the
      findings from X-ray absorption spectroscopy, indicates that the Ni(2+) binding
      site involves His229, and that Cys231 has an indirect structural role in metal
      binding. An in vivo assay of urease activation demonstrated that H229A HpUreF,
      C231A HpUreF, and H229/C231 HpUreF are significantly less competent in this
      process, suggesting a role for a Ni(2+) complex with UreF in urease maturation.
      This hypothesis was supported by calculations revealing the presence of a tunnel
      that joins the Cys-Pro-His metal binding site on UreG and an opening on the UreD
      surface, passing through UreF close to His229 and Cys231, in the structure of the
      H. pylori UreDFG complex. This tunnel could be used to transfer nickel into the
      urease active site during apoenzyme-to-holoenzyme activation. 

PMID- 24292247
TI  - Epidemiological investigation of equine piroplasmosis in China by enzyme-linked
      immunosorbent assays.
AB  - The objective of this study is to investigate the seroprevalence of equine
      piroplasmosis in China. A total of 1990 sera were collected from clinically
      healthy horses in various districts located in ten different provinces of China
      and examined by using indirect enzyme-linked immunosorbent assays (ELISAs) with
      recombinant Theileria equi (T. equi) merozoite antigen 2 (rEMA-2) and Babesia
      caballi (B. caballi) 48-kDa rhoptry protein (rBc48), respectively. The results
      showed that 1,018 (51.16%) and 229 (11.51%) samples were positive for B. caballi
      and T. equi infection, respectively. The number of samples with mixed infection
      was 152 (7.64%). These results indicated that equine piroplasmosis was widespread
      in China. 

PMID- 24292248
TI  - Dopamine: approaches to its side chain labeling with tritium.
AB  - Methods are presented to tritiate the side chain of dopamine. 

PMID- 24292249
TI  - The new facility for neutron tomography of IPEN-CNEN/SP and its potential to
      investigate hydrogenous substances.
AB  - A new facility for neutron tomography has been installed at the IEA-R1 nuclear
      research reactor of IPEN-CNEN/SP. A tomography can be obtained in 400 s and the
      spatial resolution in the image is 263 MUm. The neutron dose per tomography, in
      the video camera used for image capture, is only 21 MUSv, assures very few
      damages in its CCD sensor. Some selected objects were investigated and the
      obtained 3D images demonstrate the capability of the facility to investigate
      hydrogenous substances.

PMID- 24292250
TI  - A complexity measure based method for studying the dependance of 222Rn
      concentration time series on indoor air temperature and humidity.
AB  - We have suggested a complexity measure based method for studying the dependence
      of measured (222)Rn concentration time series on indoor air temperature and
      humidity. This method is based on the Kolmogorov complexity (KL). We have
      introduced (i) the sequence of the KL, (ii) the Kolmogorov complexity highest
      value in the sequence (KLM) and (iii) the KL of the product of time series. The
      noticed loss of the KLM complexity of (222)Rn concentration time series can be
      attributed to the indoor air humidity that keeps the radon daughters in air. 

PMID- 24292251
TI  - Retention in care and adherence to ART are critical elements of HIV care
      interventions.
AB  - Retention in care and adherence to antiretroviral treatment (ART) are critical
      elements of HIV care interventions and are closely associated with optimal
      individual and public health outcomes and cost effectiveness. This literature
      review was conducted to analyse how the roles of clients in HIV care and
      treatment are discussed, from terminology used to measurement methods to
      consequences of a wide range of patient-related factors impacting client
      adherence to ART and retention in care. Unfortunately, data suggests that clients
      find it hard to follow recommended behaviour. For HIV, the greatest loss to
      follow-up occurs before starting treatment, though each step of the continuum of
      care is affected. Measurement approaches can be divided into 'direct' and
      'indirect' methods; in practice, a combination is often considered the best
      strategy. Inadequate retention and adherence lead to decreased health outcomes
      (morbidity, mortality, drug resistances, risk of transmission) and cost
      effectiveness (increased costs and lower productivity). 

PMID- 24292253
TI  - Graphene oxide capturing surface-fluorinated TiO2 nanosheets for advanced
      photocatalysis and the reveal of synergism reinforce mechanism.
AB  - Surface-fluorinated TiO2 (F-TiO2) nanosheets with exposed (001) facets were
      synthesized from a scalable hydrothermal treatment assisted by a specific
      stabilization effect of fluorine ions on the (001) facets. Assembly of F-TiO2 on
      graphene oxide (GO) sheets into GO/F-TiO2 hybrid in aqueous solution was further
      achieved by making use of the surfactant role of GO. Photocatalytic properties of
      GO/F-TiO2 hybrid were evaluated under 365 nm UV light irradiation for
      photodegradation of methylene blue (MB). An optimal GO content has been
      determined to be 3 wt%, and the corresponding apparent pseudo-first-order rate
      constant Kapp is 0.0493 min(-1), 3 times and 4 times more than that of pure TiO2
      nanosheets and commercial P25 photocatalyst, respectively. To reveal the
      synergism reinforce mechanism of GO/F-TiO2 hybrid, photo absorption, surface
      absorption, and the photoelectrochemical current properties have been intensively
      studied. We found that enhanced electron-hole separation has been the key issue
      for the reinforcement of photocatalytic performance. F-TiO2 with exposed (001)
      facet has stronger electron-hole separation resulting in a higher
      photoelectrochemical current than that of P25 photocatalyst. Moreover,
      hybridization of F-TiO2 with GO could further increase the photoelectrochemical
      current and the largest current for the optimal weight fraction of GO is in good
      accordance with the photocatalysis performance. The GO/F-TiO2 interface junction
      that favors the electron-hole separation was attributed to the
      photoelectrochemical current enhancement. 

PMID- 24292252
TI  - Food security in the context of HIV: towards harmonized definitions and
      indicators.
AB  - Integration of HIV and food security services is imperative to improving the
      health and well-being of people living with HIV. However, consensus does not
      exist on definitions and measures of food security to guide service delivery and
      evaluation in the context of HIV. This paper reviews definitions and indicators
      of food security used by key agencies; outlines their relevance in the context of
      HIV; highlights opportunities for harmonized monitoring and evaluation
      indicators; and discusses promising developments in data collection and
      management. In addition to the commonly used dimensions of food availability,
      access, utilization and stability, we identify three components of food security
      food sufficiency, dietary quality, and food safety-that are useful for
      understanding and measuring food security needs of HIV-affected and other
      vulnerable people. Harmonization across agencies of food security indicators in
      the context of HIV offers opportunities to improve measurement and tracking,
      strengthen coordination, and inform evidence-based programming. 

PMID- 24292254
TI  - Maintenance and preservation of ectomycorrhizal and arbuscular mycorrhizal fungi.
AB  - Short- to long-term preservation of mycorrhizal fungi is essential for their in
      depth study and, in the case of culture collections, for safeguarding their
      biodiversity. Many different maintenance/preservation methods have been developed
      in the last decades, from soil- and substrate-based maintenance to preservation
      methods that reduce (e.g., storage under water) or arrest (e.g.,
      cryopreservation) growth and metabolism; all have advantages and disadvantages.
      In this review, the principal methods developed so far for ectomycorrhizal and
      arbuscular mycorrhizal fungi are reported and described given their distinct
      biology/ecology/evolutionary history. Factors that are the most important for
      their storage are presented and a protocol proposed which is applicable, although
      not generalizable, for the long-term preservation at ultra-low temperature of a
      large panel of these organisms. For ECM fungi, isolates should be grown on
      membranes or directly in cryovials until the late stationary growth phase. The
      recommended cryopreservation conditions are: a cryoprotectant of 10% glycerol,
      applied 1-2 h prior to cryopreservation, a slow cooling rate (1  degrees C min(
      1)) until storage below -130  degrees C, and fast thawing by direct plunging in a
      water bath at 35-37  degrees C. For AMF, propagules (i.e., spores/colonized root
      pieces) isolated from cultures in the late or stationary phase of growth should
      be used and incorporated in a carrier (i.e., soil or alginate beads), preferably
      dried, before cryopreservation. For in vitro-cultured isolates, 0.5 M trehalose
      should be used as cryoprotectant, while isolates produced in vivo can be
      preserved in dried soil without cryoprotectant. A fast cryopreservation cooling
      rate should be used (direct immersion in liquid nitrogen or freezing at
      temperatures below -130  degrees C), as well as fast thawing by direct immersion
      in a water bath at 35  degrees C.

PMID- 24292255
TI  - Disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical as a model of
      reactive oxygen species catalysed by Lewis and/or Bronsted acids.
AB  - Electron-transfer disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical
      (DPPH) occurred in the presence of Sc(3+) acting as a strong Lewis acid in
      deaerated acetonitrile. In contrast, in the case of weaker Lewis acids than
      Sc(3+), such as Mg(2+) and Li(+), external protons from acetic acid were required
      for the disproportionation of DPPH to occur. 

PMID- 24292256
TI  - An animal model mimicking pedunculopontine nucleus cholinergic degeneration in
      Parkinson's disease.
AB  - A rostral brainstem structure, the pedunculopontine nucleus (PPN), is severely
      affected by Parkinson's disease (PD) pathology and is regarded a promising target
      for therapeutic deep-brain stimulation (DBS). However, understanding the PPN's
      role in PD and assessing the potential of DBS are hampered by the lack of a
      suitable model of PPN degeneration. Rats were rendered Parkinsonian through a
      unilateral substantia nigra pars compacta (SNpc) stereotaxic injection of the
      proteasome inhibitor Lactacystin, to investigate whether the lesion's
      pathological effects spread to impact the integrity of PPN cholinergic neurons
      which are affected in PD. At 5 weeks post-surgery, stereological analysis
      revealed that the lesion caused a 48 % loss of dopaminergic SNpc neurons and a 61
      % loss of PPN cholinergic neurons, accompanied by substantial somatic hypotrophy
      in the remaining cholinergic neurons. Magnetic resonance imaging revealed T2
      signal hyper-/hypointensity in the PPN of the injected hemisphere, respectively
      at weeks 3 and 5 post-lesion. Moreover, isolated PPN cholinergic neurons revealed
      no significant alterations in key autophagy mRNA levels, suggesting that
      autophagy-related mechanisms fail to protect the PPN against Lactacystin-induced
      cellular changes. Hence, the current results suggest that the Lactacystin PD
      model offers a suitable model for investigating the role of the PPN in PD.

PMID- 24292257
TI  - Naso-gastric or naso-jejunal decompression after partial distal gastrectomy for
      gastric cancer. Final results of a multicenter prospective randomized trial.
AB  - BACKGROUND: Only a few, small, monocentric randomized controlled trials (RCTs)
      have compared routine vs. no placement of a nasogastric or nasojejunal tube
      decompression (NG/NJT) in patients undergoing partial distal gastrectomy (PDG)
      for gastric cancer. However, to our knowledge, no multicenter prospective RCT has
      analyzed the role of decompression after both the Billroth II (BII) procedure and
      Roux-en-Y (RY) gastrojejunostomy. The aim of this study was to determine whether
      NG/NJT prevents the consequences of postoperative ileus after PDG for gastric
      cancer after both BII reconstruction and RY. METHODS: Two hundred seventy
      patients undergoing PDG for gastric cancer were randomly assigned NG/NJT
      placement (NG/NJT group) or not (no-NG/NJT group) with either Billroth II
      gastrojejunostomy or Roux-en-Y gastrojejunostomy. The patients were monitored for
      postoperative complications, mortality, and postoperative course. RESULTS: By
      January 2010 to June 2012, among 270 patients undergoing PDG for gastric cancer,
      134 were randomly assigned to NG/NJT placement (NG/NJT group) and 136 to no
      decompression (no-NG/NJT group). Time to passage of flatus was significantly
      shorter in the NG/NJT group than in the no-NG/NJT group, but only after RY
      reconstruction (3.3 +/- 1.5 vs. 4.3 +/- 1.6 days, P < 0.001, respectively).
      Postoperative abdominal distention was significantly lower in the NG/NJT group
      than in the no-NG/NJT group after both BII and the RY procedure (P < 0.001). No
      significant differences in postoperative mortality or morbidity, especially
      anastomotic leakage or intra-abdominal sepsis, were observed between the groups.
      CONCLUSION: Routine placement of an NG/NJT after BII and RY PDG is not necessary
      in elective surgery for gastric cancer.

PMID- 24292259
TI  - Update of recommendations for Analgosedation in pediatric intensive care unit.
AB  - Effective and adequate therapy to control pain and stress are essential in
      managing children in Pediatric Intensive Care Unit (PICU) undergoing painful
      invasive procedures, this should be, but is not yet, one of our main aims. Aware
      that this difficult mission must be pursued in a systematic, multimodal and
      multitasking way, the Studying Group on Analgosedation in PICU from the Italian
      Society of Neonatal and Paediatric Anesthesia and Intensive Care (SARNePI) is
      providing its recommendations. 

PMID- 24292258
TI  - Membrane ERalpha attenuates myocardial fibrosis via RhoA/ROCK-mediated actin
      remodeling in ovariectomized female infarcted rats.
AB  - We have demonstrated that long-term 17beta-estradiol attenuated fibrosis after
      myocardial infarction, but recent evidence suggests that estrogen mediates more
      rapid cellular effects. RhoA has been shown to play a role in the control of
      myocardial fibrosis by regulating the actin-regulatory protein cofilin. We sought
      to elucidate whether RhoA activity regulates estradiol-induced fibrosis after
      infarction in ovariectomized female rats. Twenty-four hours after coronary
      ligation, female Wistar rats were randomized into control or estradiol treatment
      for 4 weeks starting from 2 weeks after bilateral ovariectomy. There were similar
      infarct sizes among the infarcted groups. Myocardial fibrosis was significantly
      reduced, as measured by hydroxyproline content, Sirius Red staining and actin
      polymerization after administering estradiol. Estradiol treatment was associated
      with RhoA/Rho kinase inhibition evidenced by increased phosphorylation of RhoA
      and decreased phosphorylation of downstream factors including cofilin.
      Administration of PPT, a specific ERalpha agonist, or a membrane impermeable
      estrogen-albumin construct also inhibited cofilin phosphorylation, suggesting
      that cofilin phosphorylation is achieved through the recruitment of a membrane
      ERalpha. The ERbeta-selective agonist, DPN, did not alter cofilin phosphorylation
      levels, but the ER antagonist, ICI 182,780 increased cofilin phosphorylation
      levels. G-15 (an inhibitor of G-protein coupled estrogen receptor) did not affect
      the phosphorylation as compared with estradiol alone. The inhibitor of Rho
      kinase, Y-27632, attenuated cofilin phosphorylation levels, similar to the effect
      produced by estradiol. These results indicate that chronic use of estradiol after
      infarction attenuates cardiac fibrosis by inhibiting RhoA/ROCK/cofilin pathway,
      which is exerted through membrane ERalpha-mediated receptor mechanism. KEY
      MESSAGE: Postinfarction was associated with increased cardiac fibrosis.
      Myocardial fibrosis was significantly reduced after administering estradiol (E2).
      Administration of the membrane ERalpha agonist PPT or E2-BSA inhibited cofilin
      phosphorylation. Combination of E2 and Y-27632 did not enhance the attenuation of
      cofilin phosphorylation. Chronic use of E2 attenuated cardiac fibrosis by
      inhibiting the RhoA/ROCK/cofilin pathway via ERalpha.

PMID- 24292260
TI  - High-volume hemofiltration in critically ill patients: a systematic review and
      meta-analysis.
AB  - BACKGROUND: High volume hemofiltration (HVHF) has been proposed as method for
      blood purification, especially under the condition of systemic inflammatory
      syndromes. Our goal was to evaluate the effects of HVHF in critically ill
      patients. METHODS: A systematic review and meta-analysis was conducted of
      randomized controlled trials containing original data comparing HVHF defined by a
      dose of >50 mL/kg/h versus standard volume hemofiltration in critically ill
      patients. The primary outcome assessed was mortality. Additional endpoints
      assessed were renal recovery, vasopressor dependency, cytokine reduction and
      adverse events. RESULTS: Four studies investigating continuous HVHF and three
      studies examining pulse high volume hemofiltration (PHVHF) using prescribed doses
      between 62 and 85 mL/kg/h met the criteria for this systematic review and
      provided data eligible for meta-analysis on a total of 558 patients. Meta
      analyses did not show an effect of continuous HVHF (odds ratio, OR: 0.85; 95%
      confidence interval [CI]: 0.50-1.45; 4 trials; N.=473) or PHVHF (OR: 0.62; 95%
      CI: 0.22-1.74; 3 trials; N.=85) on mortality (both combined: OR: 0.85; 95% CI:
      0.60-1.22; 7 trials; N.=558). Continuous HVHF had no significant beneficial
      effect on renal recovery of survivors (OR: 0.62; 95% CI: 0.17-1.97; 3 trials;
      N.=445). Inconsistent reports of a more rapid hemodynamic stabilization or
      improved cytokine clearance were mainly restricted to PHVHF. CONCLUSION: No clear
      overall beneficial effect of HVHF or PHVHF compared to standard volume
      hemofiltration can be detected.

PMID- 24292261
TI  - Hyper-Raman and Raman scattering from the polar modes of PbMg1/3Nb2/3O3.
AB  - Microhyper-Raman spectroscopy of PbMg(1/3)Nb(2/3)O(3) (PMN) single crystal is
      performed at room temperature. The use of an optical microscope working in
      backscattering geometry significantly reduces the LO signal, highlighting thereby
      the weak contributions underneath. We clearly identify the highest frequency
      transverse optic mode (TO3) in addition to the previously observed soft TO
      doublet at low frequency and TO2 at intermediate frequency. TO3 exhibits strong
      inhomogeneous broadening but perfectly fulfils the hyper-Raman cubic selection
      rules. The analysis shows that hyper-Raman spectroscopy is sensitive to all the
      vibrations of the average cubic Pm3-m symmetry group of PMN, the three polar F1u-
      and the silent F2u-symmetry modes. All these vibrations can be identified in the
      Raman spectra alongside other vibrational bands likely arising from symmetry
      breaking in polar nanoregions.

PMID- 24292262
TI  - Minocycline accelerates hypoxia-inducible factor-1 alpha degradation and inhibits
      hypoxia-induced neovasculogenesis through prolyl hydroxylase, von Hippel-Lindau
      dependent pathway.
AB  - Hypoxia-mediated stress responses are important in tumor progression, especially
      when tumor growth causes the tumor to become deprived of its blood supply. The
      oxygen-labile transcription factor hypoxia-inducible factor-1 alpha (HIF-1alpha)
      plays a critical role in regulating hypoxia stress-related gene expression and is
      considered a novel therapeutic target. Lung adenocarcinoma cell lines were
      exposed to minocycline, followed by incubation at hypoxic condition for 3-6 h.
      Here, we show that minocycline, a second-generation tetracycline, can induce HIF
      1alpha proteasomal degradation under hypoxia by increasing the expression prolyl
      hydroxylase-2 and HIF-1alpha/von Hippel-Lindau protein interaction, thereby
      overcoming hypoxia-induced HIF-1alpha stabilization. Neither repression of
      hypoxia-induced phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin
      pathway nor inhibition of Hsp90 was required for minocycline-induced HIF-1alpha
      degradation. The HIF-1alpha degradation-enhancing effect of minocycline was
      evident in both cancerous and primary cells. Minocycline-pretreated, hypoxia
      conditioned cells showed a clear reduction in hypoxia response element reporter
      expression and amelioration of vascular endothelial growth factor C/D (VEGF-C/D),
      matrix metalloproteinase 2, and glucose transporter 1 expression. By decreasing
      VEGF secretion of cancerous cells, minocycline could suppress endothelial cell
      neovasculogenesis. These findings suggest a novel application of minocycline in
      the treatment of tumor angiogenesis as well as hypoxia-related diseases.

PMID- 24292263
TI  - The effects of gemcitabine and capecitabine combination chemotherapy and of low
      dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in
      patients with advanced pancreatic cancer.
AB  - In pre-clinical models, the only two chemotherapy drugs which have been
      demonstrated to directly reduce the number of myeloid-derived suppressor cells
      (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of
      MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer
      receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We
      found no evidence that gemcitabine and capecitabine directly reduce MDSC% in
      patients. Gemcitabine and capecitabine reduced MDSCs in 42% of patients (n = 19)
      and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8
      patients with minimal tumour volume change on treatment, the MDSC% went up:
      increases in MDSC% in these patients appeared to correlate with sustained cancer
      related inflammatory cytokine upregulation. In a separate cohort of 21 patients
      treated with gemcitabine and capecitabine together with concurrently administered
      GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there
      was a significant difference in the trajectory of MDSCs between those receiving
      GV1001 and GM-CSF in combination with chemotherapy and those receiving
      chemotherapy alone. Thus, there was no evidence that the addition of low-dose
      adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination
      chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the
      MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination
      MDSC levels. A high pre-vaccination MDSC% does not preclude the development of
      immunity to a tumour-associated antigen.

PMID- 24292264
TI  - Thoracoscopic half carina resection and bronchial sleeve resection for central
      lung cancer.
AB  - BACKGROUND: The objectives of this study were to report the surgical techniques
      and clinical outcome of thoracoscopic half carina resection and thoracoscopic
      bronchial sleeve resection for central lung cancer. METHODS: Between January 2011
      and November 2012, 675 patients with lung cancer underwent radical surgery by
      thoracoscopy, and 49 (7.3%) underwent bronchial sleeve resection. Among 49
      patients, 20 (41%) received thoracoscopic bronchial sleeve lobectomy.
      Perioperative variables and postoperative outcomes of these cases were analyzed
      to evaluate the technical feasibility and safety of this operation. RESULTS: In
      one patient, right upper lung sleeve resection was combined with half-carinal
      resection and reconstruction. In another, right medial lung sleeve resection was
      combined with lower right dorsal segment resection. The average time of surgery
      was 239 +/- 51 minutes (range = 142-330 minutes), and the average time of airway
      reconstruction was 44 +/- 17 minutes (range = 22-75 minutes). The intraoperative
      blood loss averaged 207 +/- 96 mL (range = 80-550 mL). The median postoperative
      hospital stay was 10 days (interquartile range = 8-12 days). Postoperatively,
      extubation was achieved in the recovery room without further need for mechanical
      ventilation. None of the patients developed anastomotic leak. Perioperative
      mortality was not observed. CONCLUSION: Thoracoscopic bronchial sleeve resection
      can be considered a feasible and safe operation for selected patients with
      central lung cancer. The complicated anastomosis technique of half carina
      resection was feasible.

PMID- 24292265
TI  - Dissection of the right pulmonary artery after blunt trauma.

PMID- 24292266
TI  - Urgent reoperative transapical valve-in-valve shortly after a transapical aortic
      valve implantation.
AB  - Urgent reoperative transapical aortic valve-in-valve has never been proposed as a
      treatment option in case of a failed transcatheter aortic valve implantation
      (TAVI) or in case of worsening of an existing paravalvular leak, if this
      complication occurs right after, or a few days after, the primary transapical
      aortic valve implantation. Experienced surgeons should argue that after a
      transapical TAVI, the apex is damaged and fragile, with a high risk of
      irreparable ventricular tears and life-threatening bleeding if a second
      transapical procedure is scheduled during the acute phase. Nevertheless, if the
      patient is inoperable and the vascular status, including the ascending aorta,
      limits alternative accesses, the urgent reoperative transapical valve-in-valve
      becomes an alternative. We illustrate, for the first time ever, our experience
      with an 81-year old female patient who underwent a transapical (TA) TAVI with a
      Sapien XT 23 mm. The day after the procedure, the patient haemodynamically
      worsened in combination with a worsening of a known (grade 1-2) paravalvular
      leak. Thus, on postoperative day two, an urgent transapical valve-in-valve was
      performed, and a second Sapien XT 23 mm was placed, with an excellent
      haemodynamic result and absence of leak. The redo apical access did not appear
      very complicated and the postoperative recovery was uneventful.

PMID- 24292268
TI  - A nano-Si/FeSi2Ti hetero-structure with structural stability for highly
      reversible lithium storage.
AB  - A nano-Si/FeSi2Ti hetero-structure has been synthesized for highly reversible Li
      ion batteries by using a simple melt-spinning method. We demonstrate that this
      composite has a very peculiar core/shell structure in which the FeSi2Ti alloy
      plays various pivotal roles as a mechanically supporting backbone and as an
      electronic pathway for the active Si attached to its surface, and is responsible
      for the altered electrochemical reactions with relatively small volume expansion
      routes. The FeSi2Ti matrix significantly contributes to not only the
      stabilization of cyclic retention, but also the enhancement of conductivity, as
      well as a high rate capability unprecedented in research on Si-based anodes. This
      achievement demonstrates the potency of this novel hybrid design for electrode
      materials for energy storage. 

PMID- 24292267
TI  - SPOCK3, a risk gene for adult ADHD and personality disorders.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most frequent psychiatric
      disorder in children, where it displays a global prevalence of 5 %. In up to 50 %
      of the cases, ADHD may persist into adulthood (aADHD), where it is often comorbid
      with personality disorders. Due to a potentially heritable nature of this
      comorbidity, we hypothesized that their genetic framework may contain common risk
      modifying genes. SPOCK3, a poorly characterized, putatively Ca(2+)-binding
      extracellular heparan/chondroitin sulfate proteoglycan gene encoded by the human
      chromosomal region 4q32.3, was found to be associated with polymorphisms among
      the top ranks in a genome-wide association study (GWAS) on ADHD and a pooled GWAS
      on personality disorder (PD). We therefore genotyped 48 single nucleotide
      polymorphisms (SNPs) representative of the SPOCK3 gene region in 1,790
      individuals (n aADHD = 624, n PD = 630, n controls = 536). In this analysis, we
      found two SNPs to be nominally associated with aADHD (rs7689440, rs897511) and
      four PD-associated SNPs (rs7689440, rs897511, rs17052671 and rs1485318); the
      latter even reached marginal significance after rigorous Bonferroni correction.
      Bioinformatics tools predicted a possible influence of rs1485318 on transcription
      factor binding, whereas the other candidate SNPs may have effects on alternative
      splicing. Our results suggest that SPOCK3 may modify the genetic risk for ADHD
      and PD; further studies are, however, needed to identify the underlying
      mechanisms. 

PMID- 24292269
TI  - Common pharmacophore of structurally distinct small-molecule inhibitors of
      intracellular retrograde trafficking of ribosome inactivating proteins.
AB  - We reported previously (+/-)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3
      dihydroquinazolin-4(1H)-one [(+/-)-Retro-2(cycl)] as the chemical structure of
      Retro-2 that showed mouse protection against ricin, a notorious ribosome
      inactivating protein (RIP). Herein we report our chemical resolution of (+/-)
      Retro-2(cycl), analog synthesis, and cell-based evaluation showing that the two
      optically pure enantiomers and their achiral analog have nearly the same degree
      of cell protection against ricin as (+/-)-Retro-2(cycl). We also report our
      computational studies explaining the lack of stereo preference and revealing a
      common pharmacophore of structurally distinct inhibitors of intracellular
      retrograde trafficking of RIPs. This pharmacophore comprises a central aromatic
      ring o-substituted by an aromatic ring and a moiety bearing an O or S atom
      attached to sp2 C atom(s). These results offer new insights into lead
      identification and optimization for RIP antidote development to minimize the
      global health threat caused by ribosome-inactivating proteins.

PMID- 24292271
TI  - ETV as a last resort.
AB  - INTRODUCTION: The field of neuroendoscopy is rapidly expanding with increasing
      indications for endoscopic third ventriculostomy (ETV). DISCUSSION: As a
      treatment for hydrocephalus, ETV has the advantage of providing a more
      physiological cerebrospinal fluid diversion without shunt hardware which reduces
      the risk of recurrent infection and malfunction. The success rate of ETV has been
      increasing with decreasing morbidity and mortality. CONCLUSION: Originally, ETV
      was indicated for cases of obstructive hydrocephalus, however the indications are
      expanding. To highlight this, we present a small series of cases were ETV is not
      traditionally indicated and was a treatment of last choice.

PMID- 24292270
TI  - Nano-sized and micro-sized polystyrene particles affect phagocyte function.
AB  - Adverse effect of nanoparticles may include impairment of phagocyte function. To
      identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis,
      cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and
      myeloperoxidase release, leukocytes isolated from human peripheral blood,
      monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in
      sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS
      particles were taken up passively, while larger CPS particles entered cells
      actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes,
      >=500 nm CPS particles only to macrophages. Twenty nanometers CPS particles
      stimulated IL-8 secretion in human monocytes and induced oxidative burst in
      monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and
      IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic
      stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an
      oxidative burst of granulocytes. At very high concentrations, CPS particles of 20
      and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide
      generation in macrophages. Cytotoxic effect could contribute to some of the
      observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles
      appear to influence phagocyte function to a greater extent than particles in
      other sizes.

PMID- 24292272
TI  - Acyl hydrazides as acyl donors for the synthesis of diaryl and aryl alkyl
      ketones.
AB  - In this communication we describe a novel strategy for the formation of valuable
      diaryl and aryl alkyl ketones from acyl hydrazides. A wide variety of ketones are
      prepared and the mild reaction conditions allow for the use of a range of
      functionalities, especially in the synthesis of diaryl ketones. 

PMID- 24292273
TI  - EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of
      pulmonary hypertension.
AB  - Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of
      pulmonary hypertension that is characterized histologically by widespread fibrous
      intimal proliferation of septal veins and preseptal venules and is frequently
      associated with pulmonary capillary dilatation and proliferation. PVOD is
      categorized into a separate pulmonary arterial hypertension-related group in the
      current classification of pulmonary hypertension. PVOD presents either
      sporadically or as familial cases with a seemingly recessive mode of
      transmission. Using whole-exome sequencing, we detected recessive mutations in
      EIF2AK4 (also called GCN2) that cosegregated with PVOD in all 13 families
      studied. We also found biallelic EIF2AK4 mutations in 5 of 20 histologically
      confirmed sporadic cases of PVOD. All mutations, either in a homozygous or
      compound-heterozygous state, disrupted the function of the gene. These findings
      point to EIF2AK4 as the major gene that is linked to PVOD development and
      contribute toward an understanding of the complex genetic architecture of
      pulmonary hypertension. 

PMID- 24292276
TI  - Letter to the editor concerning "CT Morphology and Morphometry of the normal
      adult coccyx" [by Woon JT et al. (2013); Eur Spine J 22(4):863-870].

PMID- 24292275
TI  - Uptake and metabolic effects of salicylic acid on the pulvinar motor cells of
      Mimosa pudica L.
AB  - In this paper, the salicylic acid (o-hydroxy benzoic acid) (SA) uptake by the
      pulvinar tissues of Mimosa pudica L. pulvini was shown to be strongly pH
      dependent, increasing with acidity of the assay medium. This uptake was performed
      according to a unique affinity system (K(m) = 5.9 mM, V(m) = 526 pmol mgDW(-1))
      in the concentration range of 0.1-5 mM. The uptake rate increased with increasing
      temperature (5-35  degrees C) and was inhibited following treatment with sodium
      azide (NaN3) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), suggesting the
      involvement of an active component. Treatment with p-chloromercuribenzenesulfonic
      acid (PCMBS) did not modify the uptake, indicating that external thiol groups
      were not necessary. KCl, which induced membrane depolarization had no significant
      effect, and fusicoccin (FC), which hyperpolarized cell membrane, stimulated the
      uptake, suggesting that the pH component of the proton motive force was likely a
      driving force. These data suggest that the SA uptake by the pulvinar tissues may
      be driven by two components: an ion-trap mechanism playing a pivotal role and a
      putative carrier-mediated mechanism. Unlike other benzoic acid derivatives acting
      as classical respiration inhibitors (NaN3 and KCN), SA modified the pulvinar cell
      metabolism by increasing the respiration rate similar to CCCP and 2,4
      dinitrophenol (DNP). Furthermore, SA inhibited the osmoregulated seismonastic
      reaction in a pH dependent manner and induced characteristic damage to the
      ultrastructural features of the pulvinar motor cells, particularly at the
      mitochondrial level.

PMID- 24292274
TI  - A genome-wide association study identifies multiple susceptibility loci for
      chronic lymphocytic leukemia.
AB  - Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have
      shown that common genetic variation contributes to the heritable risk of CLL. To
      identify additional CLL susceptibility loci, we conducted a GWAS and performed a
      meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases)
      and 5,199 controls with validation in an additional 1,144 cases and 3,151
      controls. A combined analysis identified new susceptibility loci mapping to
      3q26.2 (rs10936599, P = 1.74 * 10(-9)), 4q26 (rs6858698, P = 3.07 * 10(-9)),
      6q25.2 (IPCEF1, rs2236256, P = 1.50 * 10(-10)) and 7q31.33 (POT1, rs17246404, P =
      3.40 * 10(-8)). Additionally, we identified a promising association at 5p15.33
      (CLPTM1L, rs31490, P = 1.72 * 10(-7)) and validated recently reported putative
      associations at 5p15.33 (TERT, rs10069690, P = 1.12 * 10(-10)) and 8q22.3
      (rs2511714, P = 2.90 * 10(-9)). These findings provide further insights into the
      genetic and biological basis of inherited genetic susceptibility to CLL. 

PMID- 24292277
TI  - Triple action polymer probe: carboxylic distilbene fluorescent polymer
      chemosensor for temperature, metal-ions and biomolecules.
AB  - A triple-action pi-conjugated polymer chemosensor is developed for sensing
      temperature, selective detection of copper(ii) metal-ion and biological species -
      amino acids, in two wavelength optical switches based on red-fluorescent and blue
      fluorescent molecular probes. 

PMID- 24292278
TI  - Tibial stress phenomena and fractures: imaging evaluation.
AB  - This study aims to evaluate the various imaging modalities used to diagnose
      tibial stress-fractures/phenomena and determine which of these are most useful
      and definitive. The plain film, computed tomography (CT), magnetic resonance
      (MR), and nuclear medicine findings in a 20-patient cohort, ranging from ages 10
      to 21 years with an average of 16 years, were reviewed. The male to female ratio
      was recorded as was the incidence of right or left, or bilateral extremity
      involvement. Thereafter, each imaging modality was evaluated for positive
      findings. Twelve of the patients had pretibial swelling on plain films, 10 a
      thickened cortex, to a visible fracture on plain films and 13 had increased short
      tau inversion recovery (STIR) signal in the post tibial (marrow) and pretibial
      (subperiosteum) areas on MR imaging. No CT studies were performed. One positive
      nuclear medicine study was available. Although there are a number of imaging
      modalities which can be used to evaluate the tibial stress/fracture phenomena
      problem, it would appear that plain films and MR studies are most useful. If
      plain films do not show a fracture and further information is required, an MR
      study is most appropriate.

PMID- 24292279
TI  - Nuclear magnetic resonance at up to 10.1 GPa pressure detects an electronic
      topological transition in aluminum metal.
AB  - High-sensitivity (27)Al nuclear magnetic resonance (NMR) measurements of aluminum
      metal under hydrostatic pressure of up to 10.1 GPa reveal an unexpected negative
      curvature in the pressure dependence of the electronic density of states measured
      through shift and relaxation, which violates free electron behavior. A careful
      analysis of the Fermiology of aluminum shows that pressure induces an electronic
      topological transition (Lifshitz transition) that is responsible for the measured
      change in the density of states. The experiments also reveal a sudden increase in
      the NMR linewidth above 4.2 GPa from quadrupole interaction, which is not in
      agreement with the metal's cubic symmetry.

PMID- 24292280
TI  - Copolymerization of cyclohexene oxide with CO2 catalyzed by tridentate N
      heterocyclic carbene titanium(IV) complexes.
AB  - A new class of complexes based on titanium(IV) bearing a bisanionic mer
      tridentate N-heterocyclic carbene ligand were investigated for the
      copolymerization of cyclohexene oxide with CO2. Upon addition of [PPN]X' salts,
      all complexes were found to be active and highly selective toward the formation
      of poly(cyclohexene oxide-alt-carbon dioxide).

PMID- 24292282
TI  - Retraction: Pharmacokinetics and Pharmacodynamics of a Novel
      Amoxicillin/Sulbactam/Prednisolone Intramammary Infusion in Lactating Cows after
      Repeated Administrations.
AB  - This article released online on August 9, 2013 as advance publication was
      withdrawn from consideration for publication in The Journal of Veterinary Medical
      Science at author's request.

PMID- 24292281
TI  - Acceptability of smartphone application-based HIV prevention among young men who
      have sex with men.
AB  - Young men who have sex with men (YMSM) are increasingly using mobile smartphone
      applications ("apps"), such as Grindr, to meet sex partners. A probability sample
      of 195 Grindr-using YMSM in Southern California were administered an anonymous
      online survey to assess patterns of and motivations for Grindr use in order to
      inform development and tailoring of smartphone-based HIV prevention for YMSM. The
      number one reason for using Grindr (29 %) was to meet "hook ups." Among those
      participants who used both Grindr and online dating sites, a statistically
      significantly greater percentage used online dating sites for "hook ups" (42 %)
      compared to Grindr (30 %). Seventy percent of YMSM expressed a willingness to
      participate in a smartphone app-based HIV prevention program. Development and
      testing of smartphone apps for HIV prevention delivery has the potential to
      engage YMSM in HIV prevention programming, which can be tailored based on use
      patterns and motivations for use. 

PMID- 24292283
TI  - BDNF genetic variability modulates psychopathological symptoms in patients with
      eating disorders.
AB  - The brain-derived neurotrophic factor (BDNF) gene may influence eating behavior,
      body weight and cognitive impairments. We aimed to investigate whether BDNF
      genetic variability may affect anthropometric and psychological parameters in
      patients with anorexia or bulimia nervosa (AN, BN) and/or modulate the risk for
      the disorder. A total of 169 unrelated female patients and 312 healthy controls
      were genotyped for two common BDNF single-nucleotide polymorphisms (SNPs),
      Val66Met and C-270T, and several selected tag-SNPs. Associated personality
      characteristics and psychopathological symptoms were assessed by the EDI-2 and
      SCL-90R inventories, respectively. No single SNP or haplotype played a relevant
      role in the risk for AN or BN. The rs16917237 TT genotype was significantly
      associated with increased weight (74.63 +/- 16.58 vs. 57.93 +/- 13.02) and body
      mass index (28.94 +/- 6.22 vs. 22.23 +/- 4.77) in the BN group after correcting
      for multiple testing. Haplotype analyses using a sliding window approach with
      three adjacent SNPs produced four loci of interest. Locus 3
      (rs10835210/rs16917237/C-270T) showed a broad impact on the measured
      psychopathological symptoms. Haplotypes CGC and CGT in this locus correlated with
      scores in all three scales of the SCL-90R inventory, both in AN and BN patients.
      In contrast, the results of the EDI-2 inventory were largely unaffected. These
      preliminary results suggest that variability in the BDNF gene locus may
      contribute to anthropometric characteristics and also psychopathological symptoms
      that are common but not exclusive of ED patients.

PMID- 24292284
TI  - Effects of multidisciplinary pain treatment can be predicted without elaborate
      questionnaires.
AB  - PURPOSE: Low back pain is one of the most common and expensive diseases of
      Western societies. Psychosocial factors such as low social status, depression, or
      work dissatisfaction are known to promote chronicity of low back pain. With a
      multidisciplinary approach, better outcomes can be achieved than with purely
      biomedical treatment. Optimal patient selection for multidisciplinary therapy
      reduces costs and labour. This study investigated whether elaborated
      questionnaires exceed simple items in predicting multimodal therapy success.
      METHODS: In this prospective longitudinal clinical study, 330 patients were
      followed up for six months after multidisciplinary therapy. We applied the
      patient questionnaire Heidelberg Short Early Risk Assessment Questionnaire for
      the Prediction of Chronicity in Low Back Pain (HKF-R10) that is approved and
      established for predicting chronicity in patients with acute low back pain to
      forecast the therapeutic outcome. Outcome criteria were QOL, pain reduction and
      back to work. RESULTS: With regard to outcome criteria, the HKF-R10 was unable to
      anticipate therapeutic success, but education level, depression, best pain
      condition, and helplessness predicted therapy success with an 80% probability for
      QOL improvement. CONCLUSIONS: It is not necessary to confront patients with an
      extensive and complicated questionnaire to predict the outcome of
      multidisciplinary therapy. In fact, assessing a few specific items allows better
      and easier prognosis estimation.

PMID- 24292285
TI  - Response to the comment on Schuh et al.: Angular correction and complications of
      proximal first metatarsal osteotomies for hallux valgus deformity.

PMID- 24292287
TI  - Prevalence and antimicrobial susceptibility pattern of ESBL producing isolates.
AB  - Extended spectrum beta-lactamases (ESBLs) are produced by Gram negative bacteria
      showing resistance to new generations of antimicrobial agents. This study was
      undertaken to characterize ESBL producing bacteria from 222 urinary isolates.
      Antimicrobial resistance was screened by disc diffusion test. The ESBL status was
      confirmed by double disc diffusion test (DDDT) and minimum inhibitory
      concentration (MIC) by agar dilution method by standard procedure. The study
      revealed the following distribution of ESBL producing isolates: Klebsiella spp
      (81.6%), Proteus spp (78.1%) E. coli (72.3%) and Pseudomonas spp (66.7%). All the
      isolates were sensitive to imipenem and nitrofurantoin followed by amikacin
      92.9%. A relatively higher rate of resistance to gentamicin, co-trimoxazole,
      azithromycin and quinolones were also observed for ESBL producers. The study
      suggested routine detection of ESBL and avoidance of irrational use of third
      generation cephalosporins to reduce the emergence of multidrug resistance
      bacteria following an antibiotic policy. 

PMID- 24292286
TI  - Synthetically modified bioisosteres of salicyl alcohol and their
      gastroulcerogenic assessment versus aspirin: biochemical and histological
      correlates.
AB  - The present study was conducted to synthesize nitrogen containing derivatives of
      salicyl alcohol and to investigate in vivo their ulcerogenic potential in
      comparison with aspirin in rats. The compounds [4-(2-hydroxybenzyl) morpholin-4
      iumchloride (I)] and [1,4-bis(2-hydroxybenzyl) piperazine-1,4-diium chloride
      (II)] were synthesized and their chemical structures were characterized using
      spectral data. In our previous study (Ali et al., Afr J Pharm Pharmacol 7:585
      596, 2013), both compounds showed anti-inflammatory, antinociceptive, and
      antipyretic properties in standard animal models and a greater binding affinity
      for cyclooxygenase-2 versus cyclooxygenase-1 in molecular docking and dynamics
      analysis. For in vivo studies, animals were randomly divided into four groups.
      The synthetic compounds (both at 100 or 150 mg/kg), aspirin (150 mg/kg), or
      saline vehicle was administered orally, once daily for 6 days and then tested for
      ulcerogenic activity. At the end of the procedure, gastric juice and tissues were
      collected and subjected to biochemical and histological analyses. The results of
      the study revealed that in the case of the aspirin-treated group, there was a
      significant increase in gastric juice volume, free acidity, total acidity, and
      ulcer score and a decrease in gastric pH. Moreover, histological examination of
      the gastric mucosa of the aspirin-treated group indicated morphological changes
      while neither of the synthetic compounds showed any significant ulcerogenic or
      cytotoxic properties. The results of the present study suggest that both
      compounds are free from ulcerogenic side effects and may represent a better
      alternative to aspirin. 

PMID- 24292288
TI  - Effectiveness of radioiodine therapy in treatment of hyperthyroidism.
AB  - The present non randomized clinical trial was conducted in the Center for Nuclear
      Medicine and Ultrasound, Mymensingh, Bangladesh for duration of one year. Total
      30 patients with hyperthyroidism diagnosed by clinical and biochemical profile
      were included in the study. All patients received radioiodine treatment and
      regular follow up at 1st month, 3rd month, 6th month & 9th month were done to
      evaluate clinical and biochemical status and complications. Data were analyzed by
      computer with SPSS programme using 't' test and chi-square test. In the present
      study, out of 30 respondents more than three fourth of the respondents (76.6%)
      were in the age group of 31-50 years followed by less than 30 years are group
      (16.7%) and rest of respondents were in the age group of more than 50 years
      (06.7%). Mean+/-SD and range of age of the respondents were 39.80+/-10.02 years
      and 17-65 years respectively. Among the 30 respondents 11(36.7%) were male and
      19(63.3%) were female. Male to female ratio was 1:1.73. Out of 30 patients
      26(86.7%) presented with goiter and among them 21(80.8%) has diffused goiter and
      five (19.2%) had nodular goiter. Baseline mean+/-SD, median, range of serum T3
      level were 5.24+/-3.62, 4.34, 1.48-14.65nmol/L respectively. Base line mean+/-SD,
      median range of serum T4 level were 192.25+/-99.17, 201.77, 1.75-336.25nmol/L
      respectively. Baseline mean+/-SD, median range of serum TSH level were 6.33+/
      23.93, 0.15-0.07, 130.46nmol/L respectively. In the present study serum T3, T4
      level among the respondents sharply decrease from baseline to 2nd follow up then
      gradually decrease from 2nd to 4th follow up. Serum TSH level gradually increases
      from baseline to 3rd follow up and then gradually decreases from 3rd to 4th
      follow up. The result showed radioiodine is an effective option for the treatment
      of thyrotoxicosis. 

PMID- 24292289
TI  - Camp based awareness and screening programme of cervical cancer in rural area of
      Bangladesh.
AB  - This population based cross sectional study was carried out in Muktagacha
      Upazilla Health Complex, Mymensingh, Bangladesh during the period of 26th to 28th
      June, 2012. The objective was to create awareness, to find out the precancerous
      lesion of cervix and to evaluate the effectiveness of this approach for
      prevention of cervical carcinoma. Women who were married and between 30-60 years
      and also women of below 30 years (who were married below the age of 18) were
      included in this study. All pregnant women were excluded from this study. After
      counseling, pelvic examination and VIA (visual inspection of cervix with
      application of 5% acetic acid) test was done. If the squamo-columner junction of
      cervix turned to white then it was called VIA positive (+ve) cases. Then they
      were referred to colposcopy clinic of Mymensingh Medical College with a red card
      for evaluation and management. During the 3 days campaign, 395 cases were
      examined. Among them, majority (49%) of the women were below the age of 30. It
      was observed that still 48.2% were married below the age of 18 and 31% had first
      pregnancy at an age or below 18 years. But number of grand multiparity is
      lowering now a days. Only 25% had para >=4. Others have para 1-3. During pelvic
      examination, the common cervico-uterine pathologies like chronic cervicities
      (16.5%), cervical erosion (14.4%), uterine prolapse (2.3%), cervical polyp (1%),
      myomatous polyp (0.3%) and advanced cervical carcinoma (0.5%) were also diagnosed
      clinically. Among the participants, 11.9% was detected as VIA+ve cases. A
      significant association of VIA+ve cases with low socio-economic conditions, hindu
      religion, early age at marriage and high parity were observed in this study
      (p<0.05). The findings of this study highlight the utility and need of camp based
      cervical cancer screening service at regular interval in the community. 

PMID- 24292290
TI  - A friendly approach to repair fourth degree perineal tears.
AB  - This observational study was done to make the Gynecologists familiar with the
      procedure of continuous repair of rectal mucosa and repair of the anal sphincter
      by other than figure of 8 sutures and to assess the effectiveness of the
      procedure. This study was carried out in two teaching hospitals and other two
      private hospitals in Dhaka city and out side. Total 20 patients were included in
      this study. All had fourth degree perineal tear and were repaired with the new
      approach. Follow up was carried out at 6th week, 12th week, and 24th weeks. Among
      20 patients a large number of women were mother of one child and were of 21-25
      years age group. At post operative period - wound infection was nil. Perineums
      were well established in all cases. On follow up at 24th week - pain in perineum
      and dyspareunia was nil in all cases, though this was present at early weeks in
      few cases. Faecal incontinence was absent in all patients by 24 weeks
      postoperatively. In follow up visits there was no complaint of faecal
      incontinence. In few cases pain was present in early post operative periods but
      dyspareunia was absent. So, continuous repair of anal mucosa and repair of anal
      sphincters other than figure of eight seems better regarding technical easiness,
      better compliance for the surgeon and less traumatic to the rectal mucosa and
      ultimately better results. 

PMID- 24292291
TI  - Risk factors of non-alcoholic fatty liver disease.
AB  - This case control study was carried out in Mymensingh Medical College Hospital,
      Mymensingh, Bangladesh and Dhaka Medical College Hospital, Dhaka, Bangladesh from
      November 2010 to October 2011 to find out the risk factors of non-alcoholic fatty
      liver disease. A total of 90 participants (45 cases and 45 controls) were
      included. A higher proportion of patients with age >45 years were found in case
      group compared to control (51.1% vs. 15.6%). The mean age was significantly
      higher in case group 49.8+/-12.6 years. Males demonstrated their predominance in
      both case (62.2%) and control (68.9%) groups, although the two groups did not
      differ in terms of sex distribution. Body mass index demonstrates that 26.7% of
      patients in case group were of normal weight, 46.7% overweight and 26.7% obese.
      In the control group, two-thirds (68.9%) of the patients were of normal weight
      and 24.4% overweight and 7.8% obese. Diabetes and hypertension were significantly
      present in the case group than those in control counterparts 75.6% vs. 15.6% and
      86.7% vs. 15.6 % respectively. The mean fasting blood glucose, ALT, total
      cholesterol and triglycerides were significantly higher in case group compared to
      control group 7.8+/-1.3 vs. 5.4+/-2.5mmol/L (p<0.001); 39.1+/-12.4 vs. 30.3+/
      14.1IU/L, (p=0.002); 239.9+/-14.3 vs. 183.3+/-11.4mg/dl, (p<0.001) and 183.6+/
      12.5 vs. 133.5+/-16.0mg/dl, (p<0.001) respectively. However, no significant
      difference was observed between the case and the control groups in terms of HDL
      cholesterol (35.9+/-1.2 vs. 38.0+/-1.1mg/dl, p=0.203). Majority of the patients
      in case group (88.9%) exhibited increased echogenicity of liver on ultrasonogram
      as opposed to 15.6% in the control group. 

PMID- 24292292
TI  - A comparison of GFR by modified gates method with measured creatinine clearance
      rate (CCR) & MDRD formula based estimation in type 2 diabetic subjects with
      nephropathy.
AB  - Accurate estimation of the glomerular filtration rate (GFR) is essential for the
      evaluation of patient with chronic kidney disease (CKD). The present study was a
      comparison between modified gates GFR with laboratory measured CCR & MDRD formula
      based estimated GFR method. Pre-diagnosed 180 diabetic nephropathy patients were
      selected. All the time of evaluation the blood glucose of the patients were
      controlled and serum creatinine was stable. Then CCR was done and GFR was
      estimated by Modified Gates method & MDRD method. All the patients were
      categorized in 5 stages of CKD. They were matched for age, BMI, blood pressure,
      duration of diabetes, the blood sugar and HbA1C levels. The Gates GFR in stage-2
      (70+/-13) & stage-3 (48+/-12) was closer with MDRD in stage-2 (77+/-8) and stage
      3 (43+/-7). The CCR is closer in stage-1 (110+/-52) & stage-4 (30+/-10) with MDRD
      in stage-1 (112+/-13) and stage-4 (21+/-4). Association study showed MDRD GFR had
      highest correlation with Gates GFR (r=0.86; p<0.05). The estimation of glomerular
      filtration rate (GFR) in different methods varied significantly between each
      other at different stages of chronic kidney disease (CKD) in type 2 diabetic
      nephropathy subjects. 

PMID- 24292293
TI  - Prevalence of colour blindness among the first year medical & dental students of
      Mymensingh Medical College, Bangladesh.
AB  - The purpose of this study was to detect the etiology, type and prevalence of
      colour blindness & to create awareness among the blind personnel. A survey of
      colour blindness among 239 ( male-87 & female-152) Medical and Dental first year
      students during their medical checkup before admission into Mymensingh Medical
      College in the session of 2012-2013 was done. Among them 8(male-7, female-1) were
      colour blind and prevalence was 3.35 % with a marked male predominance (male
      8.04%, female 0.66 %). In view of the potential difficulties faced by such
      personnel in clinical works, detection during medical admission allowed
      appropriate counseling regarding subject selection for their future carrier. 

PMID- 24292294
TI  - Study on serum glucose level among smear positive pulmonary tuberculosis patients
      in Bangladesh.
AB  - This case control study was carried out in the Department of Biochemistry,
      Mymensingh Medical College, Bangladesh in cooperation with the Outpatient
      Department and Medicine Units of Mymensingh Medical College Hospital, Fulbaria
      Upazilla Health Complex, Mymensingh and some DOTS centers of BRAC, a non
      government organization during the period of July 2006 to June 2007. The aim of
      the study was to explore the status of serum glucose level in smear positive
      Bangladeshi pulmonary tuberculosis patients. A total of 120 people of different
      age groups were included in this study. Subjects were divided into two groups -
      Group I (Control; n=60) - apparently healthy people selected matching by age, sex
      and socioeconomic status with the cases and Group II (Case; n=60) - people with
      smear positive pulmonary tuberculosis. Serum glucose (fasting) was estimated by
      colorimetric principle. Statistical analysis was done by using SPSS windows
      package. Among the groups, mean+/-SD of serum glucose (fasting) in Group II
      (5.91+/-1.02mmol/L) was significantly higher (p<0.001) than in Group I (4.87+/
      0.57mmol/L). It is evident from the study that serum glucose level significantly
      increases in smear positive pulmonary tuberculosis patients. 

PMID- 24292295
TI  - Prediction of oesophageal varices in cirrhosis of liver patients by serum ascitic
      albumin gradient.
AB  - This hospital based observational study was carried out to evaluate the relation
      between serum ascitic albumin gradient and oesophageal varices in cirrhosis of
      liver disease patient. This was a hospital based observational study on 50 cases
      of diagnosed cirrhosis of liver disease patients in department of medicine of
      Mymensingh medical college Hospital, Mymensingh, Bangladesh from 8th January 2012
      to 07th July 2012 for a period of 6 months. The study showed age frequency 5(10%)
      were from 21-30 years, 15(30%) were from 31-40 years 15(30%) were from 40
      50years, and 15(30%) were from >=51 years of age. Out of 50 patients, 38(76%)
      were male and 12(24%) were female patients. The etiology of liver cirrhosis was
      hepatitis B virus in 22(44%), hepatitis C virus in 4(8%), alcohol in 1(2%) and
      others in 23(46%) patients. Twenty four (48%) patients had SAAG value 1.1-1.49,
      21(42%) patients had SAAG value 1.5-1.99, 5(10%) patients had Serum Ascitic
      Albumin Gradient (SAAG) value >2.0 and 16(32%) patients had no oesophageal
      varices, 11(22%) patients had small straight varices (F1) esophageal varices,
      18(36%) patients had less than one-third of the esophageal lumen (F2) oesophageal
      varices, 5(10%) patients had more than one-third of the esophageal lumen (F3)
      esophageal varices. The degree of SAAG demonstrate significant statistical
      association with presence or absence of oesophageal varices (p=0.023) and grades
      of the oesophageal varices (p=0.001) in patients with cirrhosis of liver disease.
      So, it was predicted that the presence of oesophageal varices in cirrhosis of
      liver disease patients with high SAAG without performing endoscopy of upper GIT. 

PMID- 24292296
TI  - Evaluation of the results of operative management of lumbar spinal canal
      stenosis.
AB  - Lumber spinal canal stenosis is an important cause of low back pain and it
      frequently presents with low backache with neurogenic claudication. Operative
      management of lumbar spinal canal stenosis by decompression surgery is an
      effective method. This prospective interventional (quasi experimental) study was
      performed in patient having history of characteristic clinical features like low
      backache with radicular pain, neurogenic claudication, signs of root compression,
      positive MRI findings attending in the department of Orthopaedic Surgery and
      Neurosurgery, Dhaka Medical College Hospital and NITOR. Dhaka, from July 2008 to
      June 2010. Thirty patients were evaluated among those 18(60%) were 50 years and
      above. Male to female ratio was roughly 9:1. About 87% of the patients had
      sensory deficit and 50% had neurogenic claudication. Majority (83.3%) of the
      patients at presentation had a suffering of 12 or >12 months. Diagnosis shows
      that 3.5% of patients had L4 lesion, 60% L5, 6.5% patients had L4 & L5 and 30%
      S1. Laminectomy was done in 43.3% of patients, laminectomy and disectomy in 30%
      and laminectomy, discectomy & foraminal decompression in 26.7% of patients.
      Relief of symptoms occurred in 25(83.5%) of patients. Over three-quarter (76.7%)
      of patients exhibited minimal disability and 23.3% moderate disability based on
      Oswestry Disability Index, while by MacNab criteria, most (80%) of patients was
      excellent, 10% good and another 10% fair. Repeated measure ANOVA statistics
      showed that mean Oswestry score decreased significantly from 54.5% at baseline to
      22% at the end of 1 year (p<0.001). 

PMID- 24292297
TI  - Placental changes in pregnancy induced hypertension.
AB  - A descriptive cross sectional study was carried out in Gynae and Obstetrics &
      Pathology department of Mymensingh Medical College Hospital (MMCH) to see the
      placental changes in normal pregnant & pregnancy induced hypertensive (PIH)
      mother. Total 80 placentas were collected, 40 from normal pregnant mothers having
      no hypertension and 40 from PIH group (one from gestational hypertension, 17 from
      pre-eclampsia and 22 from eclamptic mother). Macroscopic study of the placenta
      revealed placental weight, surface area and number of cotyledons were less in
      study group. Mean placental weight in study group was 419.50gm and in control
      group was 477.50gm (p<0.001). Mean surface area in study group & control group
      were 232.29cm2 and 304.80cm2 respectively (p<0.001). Mean number of cotyledons
      were 15.39 and 17.40 in study & control group respectively (p<0.001) and lower
      diameter of umbilical cord p<0.04667. But in the present study placental
      thickness was not significant p<0.539. In PIH group, macroscopic infractions were
      more marked. There was a single umbilical artery present in one patient in PIH
      group. In PIH group syncytial knots (95%), fibrinoid necrosis (80%), VSM
      formation, sclerosis, chorangiosis and calcification were more marked. Infarction
      was present in placenta of PIH 34(85%) and in control group 8(20%). Common
      placental changes were significant in this study. So, early intervention in PIH
      is rational to get the good perinatal morbidity and mortality. 

PMID- 24292298
TI  - Rockall score for risk stratification in adult patients with non-variceal upper
      gastrointestinal hemorrhage.
AB  - The Rockall risk score is a simple, validated predictive index that may serve as
      a useful clinical decision for assessing the risk of subsequent adverse outcomes
      in patients with non-variceal upper gastrointestinal hemorrhage (UGIH). The
      observational study was carried out over a period of 6 months from 10th July,
      2012 to 09th January, 2013 in Department of Medicine, Dhaka Medical College
      Hospital, Dhaka, Bangladesh. A total of 60 patients with non-variceal UGIH were
      taken for the study during study period to see risk stratification by Rockall
      score and short term hospital outcome in non-variceal upper GI hemorrhage
      patients. Categorical variables were reported as percentage and Means and
      proportions were carried out using the Chi-square test of different variables.
      Among study population age distribution were 42(70%) <60 years, 16(26.7%) from 60
      79 years and 02(3.3%) 80 years or above and sex distribution were 39(65%) male
      and 21(35%) were female patients. Rockall score of patients 11(18.3%) had score
      1, 6(10%) had score 2, 13(21.7%) had score 3, 10(16.7%) had score 4, 6(10%) had
      score 5, 6(10%) had score 6, 4(6.7%) had score 7, 3(5.0%) had score 8 and 1(1.7%)
      had score 9. Risk stratification showed 30(50%) had low risk (score 3 or <3),
      26(43.3%) had moderate risk (score 4-7) and 4(6.7%) had high risk (score 8 or
      >8). Outcome after initial Rockall scoring and endoscopy were found that 7(11.7%)
      died, 46(76.6%) survived and 7(11.7%) patients survived with complication. This
      study showed that Rockall score of <=3 was predictive of low risk of adverse
      outcomes, and a score of >=8 was predictive of high mortality and was useful in
      identifying patients with non-variceal UGIH who had low-risk scores in order to
      triage appropriately, without affecting patient outcomes. 

PMID- 24292299
TI  - Blood pressure in different levels of BMI.
AB  - Body mass index (BMI) is an inexpensive and easy-to-perform method of screening
      for weight. In recent years, non-communicable diseases (NCD) like obesity,
      hypertension and Type-2 diabetes are on the increase in the developed and
      developing nations. This Analytical cross sectional study was done to appraise
      the effect of overweight and obesity in development of high blood pressure. This
      study was carried out in the Department of Physiology, Mymensingh Medical
      College, Mymensingh, Bangladesh from 1st July 2011 to 30th June 2012 on 180
      equally divided male and female persons between the ages of 25 to 55 years. Non
      probability purposive type of sampling technique was used for selecting the study
      subjects. Measurement of body mass index and blood pressure were done as per
      procedure. Data were expressed as mean+/-SE and statistical significance of
      difference among the groups were calculated by unpaired student's 't' test and
      Pearson's correlation coefficient tests were done as applicable. The mean+/-SE of
      Systolic blood pressure were significant at 1% level for both overweight and
      obese groups of BMI (p<0.001). The mean+/-SE of Diastolic blood pressure were
      significant at 1% level for overweight group (p<0.009) and 5% level for obese
      group (p<0.02). Systolic blood pressure and Diastolic blood pressure showed
      positive correlation with BMI where in case of Systolic blood pressure it was
      stronger. This study revealed that overweight and obese persons showed higher
      level of blood pressure. 

PMID- 24292300
TI  - Changes in lipid profile of postmenopausal women.
AB  - The study reveals that menopause leads to changes in hormonal status, metabolism
      and lipid profile. Since there is an increased risk of cardiovascular diseases
      for women after menopause, the present study is aimed at comparing the changes of
      serum lipid profile in premenopausal women with that of their postmenopausal
      counterparts. This is to enable us ascertain the relative risk of developing
      cardiovascular disease in postmenopausal women in Bangladesh. One hundred and
      eighteen (118) apparently healthy females (59 premenopausal = control and 59
      postmenopausal = case) were selected for the study. The case-control cross
      sectional study was carried out in the Department of Biochemistry, Mymensingh
      Medical College in cooperation with the Department of Gynaecology, Mymensingh
      Medical College Hospital and Community Based Medical College, Bangladesh during
      the period from January 2009 to December 2009. Data were collected through
      clinical evaluation from pre selected questionnaires and fasting blood samples
      were taken for laboratory investigations. Serum total cholesterol and their sub
      fractions- high-density lipoproteins (HDL), low-density lipoproteins (LDL) and
      triglycerides (TG) were measured by autoanalyzer using enzymatic and established
      mathematical methods. Statistical significance of difference between two groups
      were evaluated by using unpaired 't' test with the help of SPSS software package.
      The results showed statistically significant increase in total cholesterol and
      LDL cholesterol (p<0.001) of menopausal women compared to reproductive age group.
      The postmenopausal women had higher but non-significant (p=0.675) concentrations
      of triglycerides than the premenopausal women with regular menstruation. However,
      a significant reduction of HDL was present in the postmenopausal group (p<0.001)
      than the premenopausal group. Therefore, it can be concluded that menopause leads
      to changes in lipid profile by increasing total and LDL cholesterol and by
      reducing HDL cholesterol. The elevated LDL and the reduction of cardio protective
      HDL is an indication that menopause is an independent risk factor for developing
      cardiovascular disease in Bangladesh. 

PMID- 24292301
TI  - Clinical profile of 250 cases of amoebic liver abscess.
AB  - Liver abscess is an emergent public health burden with considerable morbidity.
      Its prevalence varies from country to country. This prospective study was carried
      out in the Department of Medicine, Mymensingh Medical College Hospital,
      Mymensingh and Sher-E-Bangla Medical College Hospital, Barishal, Bangladesh from
      January 2004 to December 2009 to asses clinical pictures of 250 cases of amoebic
      liver abscess. Majority of patients were male (84%) presenting with upper
      abdominal pain (96.8%). High grade fever was present in 74% cases. Vomiting &
      nausea in 29.2% while loss of appetite in 42% patients. Only 4% patients showed
      diarrhea. On examination, tenderness in right hypochondriac was the predominant
      signs (95%) associated with hepatomegaly in 80% cases. Seventy eight percent
      cases showed leucocytosis. Serum alkaline phosphatase was raised in 66% patients.
      Colour of the aspirate was chocolate/brown in 80% cases. It is our experience
      that although complications are found hardly, they may take a menacing course if
      diagnosed, managed or both at the eleventh hour. 

PMID- 24292302
TI  - Ice test in diagnosis of ocular myasthenia.
AB  - This observational, non-control, non equivalent pretest and post test descriptive
      study was carried out at Bangabandhu Sheikh Mujib Medical University (BSMMU),
      Dhaka, Bangladesh from June 2009 to December 2009 to compare the efficacy of ice
      test and repetitive nerve stimulation (RNS) in diagnosis of ocular myasthenia
      gravis. Ten patients with fluctuating ptosis (4 male and 6 female) who were
      suspected of having ocular myasthenia were included in the study. Male and female
      ratio in the study was 2:3. The mean age of the patients was 28.1 years. Positive
      response to pyridostigmine was taken as confirmation of ocular myasthenia. A
      piece of ice (2cm * 1cm) was placed over the upper eyelid for 2 minutes and the
      vertical eye lid fissure height was noted before and after the application of
      ice. Repetitive nerve stimulation was performed in the same subjects
      subsequently. Results of two tests were compared. Eight patients shows good
      (>2mm) elevation of eyelid with ice and three patients had abnormal RNS. In
      conclusion, ice test appears as more sensitive clinical test to detect ocular
      myasthenia than RNS test. 

PMID- 24292303
TI  - Predilection of zonal involvement and pattern of opacities in chest x-ray in post
      primary pulmonary tuberculosis.
AB  - A cross sectional analysis of chest radiograph was performed in 100 patients with
      tuberculosis to observe the recent trends of radiographic presentation. The study
      was done from April to December, 2009, in Sir Salimullah Medical College and
      Mitford Hospital, Dhaka, Bangladesh. The chest x-ray findings were analyzed and
      zonal involvement and pattern of opacities were categorized and compared.
      Majority of patients (45%) showed involvement of the upper zone. Dominating
      lesion was consolidation (25%). Most of the patients were between 15-40 years.
      Forty-four percent patients were sputum positive for Acid Fast Bacilli and
      cavitation was the dominant lesion among them. Chest x-ray of patients with post
      primary tuberculosis shows involvement predominantly in the upper zone of lung.
      The most common opacity was consolidation. This correlates with different studies
      done over different population. 

PMID- 24292304
TI  - Short-term outcome of magnesium sulfate infusion in perinatal asphyxia.
AB  - This randomized, single blind, controlled, clinical trial was done to see the
      effect of magnesium sulfate infusion in perinatal asphyxia. This study was
      conducted in the Department of Neonatology, Bangabandhu Sheikh Mujib Medical
      University and Dhaka Medical College Hospital from January, 2010 to October,
      2010. Total 50 term neonates having postnatal age less than 12 hours with history
      of perinatal asphyxia and had history of hypoxic ischemic encephalopathy
      (moderate or severe) were included in this study. Patients were assigned randomly
      to receive either 3 doses of magnesium sulfate infusion at 250mg/kg per dose
      (0.5ml/kg per dose) 24 hours apart (experimental group) or 3 doses of normal
      saline infusion 24 hours apart (placebo-controlled group). Both groups also
      received supportive care according to the unit protocol for perinatal asphyxia.
      Baseline characteristics of 50 neonates had no differences in gestational age,
      birth weight, gender, mode and place of delivery, parity, ANC, liquor colour and
      hypoxic-ischemic encephalopathy (HIE) staging and mean age of intervention
      between the experimental and controlled groups. The mean serum magnesium at
      admission was 1.6+/-0.3mg/dl and 1.8+/-0.4mg/dl and after 48 hours was 3.9+/
      0.6mg/dl and 1.9+/-0.2mg/dl in experimental group and in controlled group
      respectively. There was no significant difference or alteration in colour, heart
      rate, respiration, capillary filling time/blood pressure and oxygen saturation
      between the experimental and control groups. At discharge, 26% (5 of 19) of
      infants in the experimental group had neurological abnormalities, compared with
      61% (11 of 18) of infants in the control group. At discharge experimental group
      were received more (78% vs. 44%) oral feedings by sucking compared with the
      controlled group. There is no significant difference in Electroencephalographic
      (EEG) abnormalities between groups. Good short-term outcomes at discharge were
      seen more (60% vs. 32%) in the experimental group, compared with the placebo
      controlled group. The overall mortality rate in our study was 26%. Postnatal
      magnesium sulfate infusion is effective in improving short-term outcomes in
      neonate with perinatal asphyxia. 

PMID- 24292305
TI  - Echocardiographic assessment of cardiac involvement in systemic lupus
      erythematosus patients.
AB  - This study was designed to assess cardiac abnormalities in patients with systemic
      lupus erythematosus (SLE) by echocardiography. It was an analytic type of cross
      sectional study, conducted in lupus clinic, Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka, Bangladesh from July 2008 to June 2009. Fifty lupus
      patients, diagnosed on the basis of ACR criteria, without cardiovascular
      symptoms, were enrolled in the study and were evaluated by standard
      echocardiography with color Doppler. SLEDAI was applied for assessment of disease
      activity. Out of 50 patients 80% had abnormal echocardiographic findings.
      Pericardial thickening was found in 38% patients, pericardial effusion 20%,
      diastolic dysfunction 72%, hypokinesia of ventricular wall 8%, overall valvular
      abnormalities 20%, commonest being aortic regurgitation (12%), followed by mitral
      regurgitation (8%), and 6% had pulmonary hypertension. Males (100%) were more
      vulnerable to cardiac involvement than females (68.2%) and later age of disease
      onset (31-40 years) was associated with higher (87.5%) chance of echo
      abnormalities. The differences, however, were not statistically significant
      (p>0.05). There was significant relationship between disease duration and cardiac
      abnormalities (p<0.01). Active disease (80.08%) was associated with higher
      frequency of cardiac involvement than disease in remission (62.50%) but the
      result was not statistically significant (p=0.151). Cardiac abnormalities are
      very common in lupus patients even when clinically asymptomatic from cardiac
      aspect. Echocardiography is an excellent non-invasive tool for cardiac
      evaluation. These observations emphasize a need for further assessment of early
      intervention to reduce subsequent cardiac morbidity and mortality among the lupus
      patients. 

PMID- 24292306
TI  - Socio-demographic characteristics and risk factors of ante-partum fetal death in
      a tertiary care hospital in Dhaka City.
AB  - The objectives of this study were to assess the socio-demographic profile and to
      identify the risk factors of ante-partum fetal death which occurs after the age
      of viability of fetus. This prospective observational study was conducted in the
      Obstetrics and Gynaecology department of Ad-din Women Medical College Hospital
      from June 2009 to July 2010. A total of 14,015 pregnant patients were admitted in
      the study place after the age of viability, which was taken as 28 weeks of
      gestation for our facilities. Eighty-three (0.59%) of them were identified as
      intrauterine fetal death. Assessment of maternal socio-demographic
      characteristics and maternal-fetal risk factors were evaluated with a semi
      structured questionnaire which was pre-tested before executing in this study.
      Majority (81.92%, n=68) of the patients were below 30 years of age, 78.31%
      belonged to middle socioeconomic group. Almost 58% women had education below
      secondary school certificate (SSC) level and 28.91% took regular antenatal
      checkup. About 61.45% patients were multi-gravida. Most (59.04%) ante-partum
      deaths were identified below 32 weeks of pregnancy. Out of 83 patients, maternal
      risk factors were identified in 41(49.59%) cases where fetal risk factors were
      found in 16(19.27%) cases; no risk factors could be determined in rests.
      Hypertension (48.78%), diabetes (21.95%), hyperpyrexia (17.3%), abruptio
      placentae (4.88%) and UTI (7.36%) were identified as maternal factors; and
      congenital anomaly (37.5%), Rh incompatibility (37.5%), multiple pregnancy
      (12.5%) and post-maturity (12.5%) were the fetal risk factors. Here, proximal
      biological risk factors are most important in ante-partum fetal deaths. More
      investigations and facilities are needed to explain the causes of ante-partum
      deaths. 

PMID- 24292307
TI  - Serum-ascites albumin gradient in differential diagnosis of ascites.
AB  - The present study was aimed to find out causes of ascites based on serum-ascites
      albumin gradient (SAAG) and to compare the diagnostic accuracy of the serum
      ascites albumin gradient, proposed as a new biochemical criterion for the
      differential diagnosis of ascites and to evaluate the value of serum-ascites
      albumin gradient in differential diagnosis of ascites. This study includes 50
      patients with ascites admitted in Medicine wards of Comilla Medical College
      Hospital, Comilla during the period of July 2010 to June 2011. Blood was drawn
      from the antecubital vein and ascetic fluid was obtained by paracentesis at the
      same time. Determination of the concentrations of albumin in both the serum and
      the ascitic fluid was carried out simultaneously. Considering SAAG value of
      >=1.1g/dl is high SAAG and a SAAG value <1.1g/dl is low SAAG. Out of 50 patients,
      male patients were 36 and female patients were 14. Male and female ratio was
      2.5:1. Age range was 21 years to 70 years. Most of the patients fall in age group
      of 41-50(28%).Among the 50 patients with ascites, cirrhosis of liver accounted
      for 68%, followed by tubercular peritonitis 12%, nephrotic syndrome 8%,
      congestive cardiac failure 6%, hepatocellular carcinoma 4% and malignancy related
      2%. In this study serum ascites albumin gradient accurately identified the cause
      of ascites in 97% cases. In contrast the exudate-transudate concept identified
      only 83% correctly. Serum ascites albumin gradient was found superior to the
      exudate-transudate concept. So, differential diagnosis of ascites should be based
      on the serum ascites albumin gradient which is a better distinguishing marker. 

PMID- 24292308
TI  - Microscopic impacts of gestational diabetes mellitus on the umbilical cord.
AB  - This observational study was done among the different types of diabetes,
      gestational diabetes mellitus (GDM). In the present study we looked for the
      microscopic impacts of GDM on the umbilical cord. This study was carried out in
      the department of Anatomy, Chittagong Medical College from May 2006 to April
      2007. Total fifty umbilical cords with placenta were collected from selected
      subjects within 36 to 40th weeks of gestation and divided them into two groups.
      Twenty five control group (specimen collected from normal mothers) and 25 GDM
      group (specimen collected from mothers developing diabetes during pregnancy
      state). Tissues from a particular area of the umbilical cord were processed for
      histological study by routine procedure. All the slides were examined under light
      microscope. In GDM group light microscopy showed rupture and erosion of the
      endothelium and complete rupture of the umbilical vessels resulting in
      extravasation of blood within Wharton's jelly. The umbilical vein was grossly
      dilated and thin walled. Smooth muscles of the umbilical vessel showed disruption
      and degeneration of its fibers. Wharton's jelly showed alteration in the pattern
      of distribution and degeneration of its fibers with honeycomb like empty spaces
      among them. It is suggested that GDM might have some harmful effects on the
      umbilical vessels and connective tissue component of the Wharton's jelly. 

PMID- 24292309
TI  - Efficacy of levamisole for the treatment of slow spreading vitiligo.
AB  - Levamisole can be used as an immunomodifier for an effective treatment of
      vitiligo. A clinical trial was done to assess the efficacy of levamisole in
      patients of vitiligo. The study was conducted in the department of Dermatology
      and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
      from January 2010 to July 2011. A total number of sixty patients were assigned
      purposively. Among them thirty patients were belonged to Group A, treated with
      levamisole alone and another thirty patients belonged to Group B, treated with
      levamisole 160 mg weekly with topical 0.1% fluocinolone acetonide acetate on the
      lesions once a day for a duration of 6 months. Patients were followed up every 2
      weeks interval and were continued up to 6 weeks. Out of all patients from group
      A, the mean sizes of the lesions were 8.17cm before treatment but 5.90cm, 4.32cm,
      and 3.57cm at 1st visit, 2nd visit and 3rd visit respectively after treatment. In
      Group B, the mean sizes of the lesions were 7.50cm before treatment but 4.92cm,
      3.00cm, and 4.75cm at 1st visit, 2nd visit and 3rd visit respectively after
      treatment. Among the respondents of Group A & B, 25(83.3%) and 27(90%) were cured
      respectively. This study observed that Levamisol with topical 0.1% fluocinolone
      was more responsive in percentage but the difference was not statistically
      significant. 

PMID- 24292310
TI  - Histological scoring and associated risk factors of non-alcoholic fatty liver
      disease.
AB  - Non alcoholic steatohepatitis is a hepatic disorder with histological features of
      alcohol induced liver disease that occurs in individual who do not consume
      significant alcohol. Liver biopsy is an important part of the evaluation in term
      of both grade & stage. A cross sectional study was carried out in the department
      of Pathology, Dhaka Medical College, Dhaka & department of Hepatology,
      Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2007 to June 2009.
      Total 55 adult subjects of both sex were included on the basis of predefined
      inclusion & exclusion criteria in this study to evaluate the histological pattern
      of non alcoholic fatty liver disease (NAFLD) and its correlation with risk
      factors. Liver biopsy was done and H & E and Masson's Trichrome stain slides were
      examined to evaluate the grade and stage of NAFLD. Scoring and semiquantitative
      assessment of steatosis and NAFLD severity was done according to Kleiner scale
      known as NAFLD activity score (NAS). The results of Pearson correlation showed
      only BMI and triglyceride level significantly correlated with NAS score. The
      results of Spearman's rank correlation showed that BMI, central obesity,
      triglyceridaemia and age significantly correlated with staging of fibrosis. The
      results of multiple regression analysis showed that variation of NAS depend on
      BMI and triglyceride level. The study also revealed that risk factors contributed
      about 29% risk for the occurrence of non alcoholic steatohepatitis. 

PMID- 24292311
TI  - Bioavailability and plasma concentration of omeprazole in healthy bangladeshi
      population after ingestion.
AB  - This cross-sectional observational study was conducted in the department of
      Gastroenterology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
      Plasma concentration of omeprazole was assayed in the quality control laboratory
      of Novartis (Bangladesh) Limited, Tongi, Gazipur, Bangladesh. The study was
      conducted from January 2006 to April 2007 and was designed to find out the
      bioavailability of omeprazole in capsule form in healthy Bangladeshi population
      and to compare this with that of the other population in the world. Twelve
      healthy volunteers were included in this study. The subjects were divided into
      two groups; six of them were randomly selected in each. One group received 40mg
      omeprazole intact capsule of one trade and other group received 40mg omeprazole
      intact capsule of another trade once daily for consecutive 8 days at 8.00 hours
      on each day. On the first and eight days of dosing, 10ml of blood sample was
      collected from each subject at 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 and 6.0 hours
      after dosing. Blood samples were centrifuged at 2500rpm for 15 minutes and plasma
      was stored at 20 degrees C. Omeprazole concentration in plasma was determined
      using a reverse phase high performance liquid chromatography (HPLC). From the
      concentration, the area under the curve (AUC) of omeprazole was determined for
      each subject by the trapezoidal rule. From the result it was observed that the
      plasma concentration of omeprazole was increased up to 6 hours in both trade-A
      and trade-B in day 1 and 8. Thus the AUC of omeprazole was also increased. But
      most of the studies in western population showed that the maximum plasma
      concentration was within 0.5 to 2.0hours indicating a difference from that of
      western studies. In this study all the subjects exhibited increased plasma
      concentration and AUC which may be due to genetic variation of omeprazole
      metabolism as an Asian which may be due to slow or "Poor metabolizers" (PMs), of
      the study population, who are deficient in CYP2C19. It is revealed that the
      plasma concentration and AUCs of both the products after single and repeated
      doses of omeprazole capsule were higher in comparison to other studies in western
      population. 

PMID- 24292312
TI  - Dengue infection in Dhaka City, Bangladesh.
AB  - Dengue fever (DF) and dengue haemorrhagic fever (DHF) are now endemic in
      Bangladesh with outbreaks being reported quite frequently. This cross sectional
      study was done clinically suspected dengue patients were selected from different
      hospitals of Dhaka city, Bangladesh, from January 2008 to December 2008. The
      clinical features, risk factors and laboratory findings associated with dengue
      infection were investigated among 201 clinically suspected patients. Antibodies
      were detected in 137(68.2%) cases. Of these, 80(58.4%) were primary and 57(41.6%)
      as secondary dengue cases according to presence of dengue-specific IgM and/or IgG
      antibodies. Among primary cases, 70(87.5%) were DF and 10(12.5%) were DHF cases,
      in contrast to secondary cases, where 10(18.1%) were DF and 47(81.9%) were DHF
      cases. Majority (57.9%) of patients presented with Grade I and 42.1% had Grade II
      disease. Patients between 16-30 years were the most vulnerable age group (81.3%
      DF and 71.9% DHF patients). Males out-numbered females with 72.5% male vs. 27.5%
      female patients having DF and 68.4% male vs. 31.6% female patients having DHF.
      The monsoon period was the peak season for dengue infection. Headache and
      arthralgia were the most frequent symptoms in both DF and DHF, but vomiting was
      more common in DHF. The Tourniquet test was significantly positive among DHF than
      DF cases (p = 0.001). Platelet count was the only laboratory parameter that
      showed significantly higher values among DHF than DF cases (p = 0.001). 

PMID- 24292313
TI  - Comparative efficacy of methotrexate and mini pulse betamethasone in the
      treatment of lichen planus.
AB  - A clinical trial was conducted to evaluate the efficacy of methotrexate and mini
      pulse betamethasone in the treatment of lichen planus. A total of forty four
      patients of lichen planus, attending at the department of Dermatology and
      Venereology, BSMMU, Dhaka, Bangladesh during the period of January 2009 to
      December 2010 were enrolled in this study. Of them, 23 patients in Group A (case)
      and 21 patients in Group B (control) were selected. The case was treated with
      oral methotrexate and the control was treated with betamethasone oral mini-pulse
      therapy. Efficacy of drugs were measured to assess the improvement of
      mucocutaneous lesions, to change the colour of the lesions which became
      violaceous to postinflammatory hyperpigmentation, remission of itching,
      disappearance of existing lesions and stop appearance of new lession after
      initiation of treatment at 1st week, 2nd week, 6th week and 12th week. At the end
      of the present study, it was found that 16(69.6%) patients in cases completely
      cured the disease, whereas 10(47.6%) patients among the control cured the
      disease. Data showed that moderate remission was higher among the control
      6(28.6%) compared to cases 5(21.7%) and the partial remission was also higher
      among the control 5(23.8%) compared to cases 2(8.7%). However, the efficacy was
      better in patients taking methotrexate and it also showed that macular and
      papular lesion responded well than plaque type lesion. Differences in treatment
      outcome were seen better in methotrexate group but the difference was not
      statistically significant. 

PMID- 24292314
TI  - Instrumented posterior lumbar interbody fusion (PLIF) with interbody fusion
      device (Cage) in degenerative disc disease (DDD): 3 years outcome.
AB  - This prospective interventional study carried out at Bangabandhu Sheikh Mujib
      Medical University and a private hospital in Dhaka, Bangladesh during the period
      from October 2003 to September 2011. Surgical treatment of degenerative disc
      disease (DDD) should aim to re-expand the interbody space and stabilize until
      fusion is complete. The present study conducted to find out the efficacy of using
      interbody fusion device (Cage) to achieve interbody space re-expansion and fusion
      in surgical management of DDD. We have performed the interventional study on 53
      patients, 42 female and 11 male, with age between 40 to 67 years. All the
      patients were followed up for 36 to 60 months (average 48 months). Forty seven
      patients were with spondylolisthesis and 06 with desiccated disc. All subjects
      were evaluated with regard to immediate and long term complications, radiological
      fusion and interbody space re-expansion and maintenance. The clinical outcome
      (pain and disability) was scored by standard pre and postoperative
      questionnaires. Intrusion, extrusion and migration of the interbody fusion cage
      were also assessed. Forty seven patients were considered to have satisfactory
      outcome in at least 36 months follow up. Pseudoarthrosis developed in 04 cases
      and 06 patients developed complications. In this series posterior lumbar
      interbody fusion (PLIF) with interbody cage and instrumentation in DDD showed
      significant fusion rate and maintenance of interbody space. Satisfactory outcome
      observed in 88.68% cases. 

PMID- 24292315
TI  - Grading of perinatal asphyxia by clinical parameters and agreement between this
      grading and Sarnat & Sarnat stages without measures.
AB  - A cross sectional study was done in Neonatal unit of Dhaka Shishu Hospital (DSH)
      to develop a grading system of perinatal asphyxia by clinical parameters, to show
      an agreement between this grading and Sarnat & Sarnat stages and to assess the
      outcome. Consecutive 60 cases of asphyxiated term newborn, aged between 0-48
      hours were enrolled in this study who were classified according to new proposed
      scoring and Sarnat & Sarnat staging system simultaneously on same set up. All
      asphyxiated cases were managed as per protocol of neonatal unit of this hospital
      and followed up accordingly till 3 months of age. Out of 60 cases, sarnat stage-I
      cases were 16 of which all were mild according to proposed scoring system. Sarnat
      stage-II cases were 20 and among them 2 were mild, 16 were moderate and 2 were
      severe according to proposed scoring system. Sarnat stage-III cases were 24,
      among them 24 were severe according to proposed scoring system. The level of
      agreement between proposed scoring & Sarnat staging was 93.3% where kappa value
      was 0.899. Overall mortality of asphyxiated cases was 33.3%. About 42.9% of
      Sarnat stage-II and 80%(8) of Sarnat stage-III cases had neurological deficit
      whereas 50%(3) of moderate and 80%(4) of severely asphyxiated cases had
      neurological deficit on follow up at 3 months of age. Brief clinical grading
      system is more convenient & easier than that of Sarnat & Sarnat staging. But it
      is also equally as effective as Sarnat staging in classifying asphyxiated babies
      into different grades & to assess the outcome of perinatal asphyxia. 

PMID- 24292316
TI  - Acute invasive fungal rhinosinusitis: our experience in immunocompromised host.
AB  - Acute invasive fungal rhinosinusitis (AIFRS) is a potentially fatal infection
      that usually affects immunocompromised patients. Early diagnosis and treatment,
      including aggressive surgical debridement, antifungal medication and correction
      of underlying predisposing factors are essential for recovery. The records of 13
      patients histopathologically diagnosed with invasive fungal rhinosinusitis were
      retrospectively reviewed. Demographic data, presenting symptoms and signs,
      underlying diseases, and outcomes of the patients are presented. The most common
      underlying disease was diabetes mellitus. Mucoraceae (n-8) and aspergillus (n-5)
      were the main fungi found in AIFRS. Mucosal biopsy confirmed fungal invasion to
      the nasal mucosa in all cases. Computed tomography and endoscopic findings showed
      a predominance of unilateral disease, with various stages of nasal involvement.
      All patients underwent surgical debridement and systemic antifungal therapy
      immediately after diagnosis. Four patients died due to AIFRS. A poor prognosis
      was detected to the extensiveness of AIFRS and to the underlying disease
      (patients with diabetes and haematological diseases had the worst outcomes), but
      not to fungus isolated. Invasive fungal rhinosinusitis is discussed in light of
      the current literature. 

PMID- 24292317
TI  - Hernioplasty for ventral hernias: correlation of wound morbidity with body mass
      index.
AB  - To determine the correlation of wound morbidity especially serum drain output in
      on lay mesh hernioplasty with Body Mass Index (BMI). This prospective descriptive
      study was conducted at Hamdard University Hospital and Jamal Noor Hospital from
      January 2010 to December 2011. A total of 42 females with ventral hernias were
      included. According to BMI, patients were divided in two groups. Group 1(G-1)
      included patients with BMI <=29.9 and Group 2(G-2) included patients with BMI
      >=30. All patients underwent hernioplasty by conventional open method (on lay
      technique). Wound was closed over a vaccum drain (16 Fr). Total drain output, the
      number of days drain kept, clinical seroma formation & need of aspiration after
      removal of drain, discharge from the wound and wound infection were recorded and
      analyzed on SPSS version 15 by using sample 't' test. A total of 42 female
      patients, 21 in each group, were included with the mean age of 46.95 years. Size
      of hernial defect was 4.80cm in G-1 and 4.61cm in G-2. Mean drain out- put in G-1
      was 134.05ml while in G-2 it was 244.29ml (p=0.008). Duration of drainage in G-1
      was 3.71 days and in G-2 was 5.24 days (p=0.028). Seroma formation and serous
      discharge from the wound occurred in 2(4.76%) patients, both were from Group-1
      and they required aspiration once only. Wound infection occurred in 4(9.52%)
      patients, and all were in Group 2. Post operative drain output in on lay mesh
      hernioplasty is directly proportional to the Body Mass Index (BMI) and these are
      the patients who require a longer period of drainage therefore this fact should
      be explained to obese patients in pre operative informed consent. 

PMID- 24292318
TI  - Predictors of knowledge towards malaria of rural tribal communities in Dhalai
      District of Tripura, India.
AB  - Reduction of malarial morbidity and mortality is one of the top public health
      priorities in Tripura and the Country. To achieve these targets it is imperative
      to have active community participation to control malaria. Community
      participation in turn depends on people's knowledge and attitude towards the
      disease. This study was conducted to examine the factors that predict the
      knowledge of rural tribal communities in Dhalai district of Tripura towards
      malaria. This community based epidemiological cross-sectional descriptive study
      was carried out in Dhalai district of Tripura. A pre-tested structured
      questionnaire collecting socio-demographic and malaria-related KAP information
      was administered to the 216 adult respondents from a representative sample of
      households. As a whole, there were 147(68.1%) illiterate respondents. Out of
      them, 89(41.2%) persons were male and 58(26.9%) were female. Correct knowledge
      about the cause of malaria was 2.77 times higher in males than females and 11.53
      times higher in literate tribal people than in illiterate. Correct knowledge
      about the symptoms fever, chills, and rigors of malaria were also higher in male
      sex and in literate tribal people. Use of smoke as preventive measure was very
      high among the respondents. Common predictors of correct knowledge about etiology
      and clinical features of malaria were in male Tripuri and Reang community. Use of
      smoke for killing of adult mosquito was predicted by illiteracy. Promotion of
      literacy and participation in health education are vital component in terms of
      knowledge and practice. 

PMID- 24292319
TI  - Live worm in gallbladder: a case report.
AB  - Ascariasis, the most common helminthic infection is caused by ascaris
      lumbricoides. Usually the adult worm lives in the small intestine. Rarely it
      migrates through the papilla of vater and may enter the common bile duct. We are
      reporting a case of live worm in gall bladder. Presence of Ascaris lumbricoides
      in gallbladder is rare entity as it is difficult to reach there due to narrow and
      tortuous cystic duct. 

PMID- 24292320
TI  - Pulmonary alveolar microlithiasis (PAM) in a child.
AB  - A 4 year 7 month-old girl of consanguineous parents presented with only fever for
      25 days but no cough or respiratory distress. Ches x-ray showed bilateral diffuse
      nodulo-striate opacities in both lungs. Investigations for any infection were
      negative including tuberculosis. Thoracoscopic biopsy showed alveolar microliths
      on histopathology suggesting the diagnosis of pulmonary alveolar microlithiasis
      (PAM). 

PMID- 24292321
TI  - Cutaneous metastatic adenocarcinoma - a case report.
AB  - Cutaneous metastases from carcinoma are relatively uncommon in clinical practice
      but they are very important to recognize. Cutaneous metastases may herald the
      diagnoses, can lead to accurate diagnoses and timely treatment. A high index of
      suspicion is required because the clinical finding may be subtle. The patient of
      cutaneous metastases may present with rapidly developing nodules or tumors.
      Although asymptomatic in most instances, Pain and tenderness may be noted. Here
      we described a 38 year old male who presented with fever, anorexia, weight loss
      and multiple painful nodules, plaques and tumors on his scalp, face, upper trunk
      and proximal portion of the upper limbs. This case present with cutaneous
      metastatic adenocarcinoma with atypical presentation and detection of cutaneous
      metastasis before primary tumor detection. 

PMID- 24292322
TI  - A high risk critical mitral valve stenosis with emergency management at Apollo
      Hospitals Dhaka.
AB  - Heart valve surgery in high-risk patients with severe jaundice, congestive
      hepatomegaly and renal impairment is associated with considerable morbidity and
      mortality. Without operation the consequences are invariably grave. A 35 years
      old gentleman with congestive cardiac failure was initially treated in coronary
      care unit (CCU). Mitral valve area was 0.5cm2, pulmonary arterial systolic
      pressure (PASP) was 110mmHg, serum bilirubin was 20mg/dl, SGPT & SGOT were
      1024iu/l and 1027iu/l respectively. Serum creatinine was 3.35mmol/l. Serum
      bilirubin gradually diminished to 3.1mg/dl after 12 days treatment in Coronary
      Care Unit but next day it increased to 3.6mg/dl. Mitral valve was replaced on an
      emergency basis. Echocardiogram on the 5th post operative day showed well
      functioning prosthetic mitral valve in situ. Serum bilirubin decreased to
      2.2mg/dl, SGPT, SGOT and serum creatinine to 43iu/l, 40iu/l and 1.34mmol/l
      respectively. After 8 weeks of postoperative follow up his serum bilirubin
      decreased to 0.8mg/dl. 

PMID- 24292323
TI  - A successful pregnancy outcome following abdominal metroplasty.
AB  - A 35 years old lady presented to Out Patients Department of Bangabandhu Sheikh
      Mujib Medical University for secondary subfertility with history of recurrent
      abortion. She was diagnosed a case of bicornuate uterus following laparoscopy.
      After 3 months of her last abortion she was advised for metroplasty. Metroplasty
      was done, forming a single cavity. Dye test was positive on right side and
      negative on left side. After 3 months of metorplasty hysterosalphingography (HSG)
      was done and reports shows bilateral patent uterine tubes. One year after
      metroplasty. She was pregnant with letrozole and Gonadotrophin. Her pregnancy was
      diagnosed by ultrasonography and advised for admission. She was on regular
      antenatal follow up and all investigation was done. Anomaly scan was done at 20
      weeks of pregnancy. She was properly immunized. Pregnancy period was uneventful
      until 37 weeks. At 37 weeks LUCS was done. A female healthy baby was born. APGAR
      score was 7/10 at 1, 10/10 at 5 minutes, baby weight 2.8kg postpartum period was
      uneventful. After abdominal metroplasty successful pregnancy outcome was
      occurred. 

PMID- 24292325
TI  - Differentially disrupted functional connectivity of the subregions of the
      inferior parietal lobule in Alzheimer's disease.
AB  - Recent research on Alzheimer's disease (AD) has shown that the altered structure
      and function of the inferior parietal lobule (IPL) provides a promising indicator
      of AD. However, little is known about the functional connectivity of the IPL
      subregions in AD subjects. In this study, we collected resting-state functional
      magnetic resonance imaging data from 32 AD patients and 38 healthy controls. We
      defined seven subregions of the IPL according to probabilistic cytoarchitectonic
      atlases and mapped the whole-brain resting-state functional connectivity for each
      subregion. Using hierarchical clustering analysis, we identified three distinct
      functional connectivity patterns of the IPL subregions: the anterior IPL
      connected with the sensorimotor network (SMN) and salience network (SN); the
      central IPL had connectivity with the executive-control network (ECN); and the
      posterior IPL exhibited connections with the default-mode network (DMN). Compared
      with the controls, the AD patients demonstrated distinct disruptive patterns of
      the IPL subregional connectivity with these different networks (SMN, SN, ECN and
      DMN), which suggests the impairment of the functional integration in the IPL.
      Notably, we also observed that the IPL subregions showed increased connectivity
      with the posterior part of the DMN in AD patients, which potentially indicates a
      compensatory mechanism. Finally, these abnormal IPL functional connectivity
      changes were closely associated with cognitive performance. Collectively, we show
      that the subregions of the IPL present distinct functional connectivity patterns
      with various functional networks that are differentially impaired in AD patients.
      Our results also suggest that functional disconnection and compensation in the
      IPL may coexist in AD. 

PMID- 24292324
TI  - Is silence golden? Effects of auditory stimuli and their absence on adult
      hippocampal neurogenesis.
AB  - We have previously hypothesized that the reason why physical activity increases
      precursor cell proliferation in adult neurogenesis is that movement serves as non
      specific signal to evoke the alertness required to meet cognitive demands.
      Thereby a pool of immature neurons is generated that are potentially recruitable
      by subsequent cognitive stimuli. Along these lines, we here tested whether
      auditory stimuli might exert a similar non-specific effect on adult neurogenesis
      in mice. We used the standard noise level in the animal facility as baseline and
      compared this condition to white noise, pup calls, and silence. In addition, as
      patterned auditory stimulus without ethological relevance to mice we used piano
      music by Mozart (KV 448). All stimuli were transposed to the frequency range of
      C57BL/6 and hearing was objectified with acoustic evoked potentials. We found
      that except for white noise all stimuli, including silence, increased precursor
      cell proliferation (assessed 24 h after labeling with bromodeoxyuridine, BrdU).
      This could be explained by significant increases in BrdU-labeled Sox2-positive
      cells (type-1/2a). But after 7 days, only silence remained associated with
      increased numbers of BrdU-labeled cells. Compared to controls at this stage,
      exposure to silence had generated significantly increased numbers of BrdU/NeuN
      labeled neurons. Our results indicate that the unnatural absence of auditory
      input as well as spectrotemporally rich albeit ethological irrelevant stimuli
      activate precursor cells-in the case of silence also leading to greater numbers
      of newborn immature neurons-whereas ambient and unstructured background auditory
      stimuli do not. 

PMID- 24292326
TI  - Applications of pentafluorophenyl boron reagents in the synthesis of heterocyclic
      and aromatic compounds.
AB  - Recently, main group reagents have attracted a lot of attention in bond-forming
      reactions in organic synthesis. This article highlights the use of
      pentafluorophenyl substituted boron reagents in their reactions with C=C and C=C
      pi-bonds for the synthesis of heterocyclic and aromatic compounds. These
      cyclisation reactions fall into four general classes although there is some
      overlap between classes and often combinations of these different types of
      reactivity are observed in the formation of the final heterocyclic product: (i)
      1,2- (and 1,4-) additions of nucleophile and Lewis-acidic boron centre, (ii) 1,1
      carboboration, (iii) carbocation rearrangements and (iv) cycloaddition chemistry.
      In addition, the prospect of using such boron reagents catalytically in the
      synthesis of aromatic compounds such as oxazoles and dibenzopentalene derivatives
      is emphasised.

PMID- 24292327
TI  - The role of sex on stability and change of depression symptom subtypes over 20
      years: a latent transition analysis.
AB  - Prospective studies investigating the long-term stability of depression symptom
      subtypes are rare. Moreover, sex has received little attention as a predictor.
      This study aimed to investigate the role of sex on stability and transition
      patterns of depressive symptom subtypes over 20 years. The data were drawn from
      three follow-ups (1988, 1999, and 2008) of the longitudinal Zurich Study. Latent
      transition analyses were fitted to the data of 322 subjects, using depressive
      symptoms from the face-to-face interviews. The stable classes were characterized
      by psychosocial correlates. Three subtypes were identified: 'severe atypical,'
      'severe typical,' and 'moderate.' While stability of the severe atypical and
      moderate subtype was relatively high and increased over time (70-71; 45-90%),
      stability of the severe typical subtype was lower (45-48%). Females had a higher
      risk of being in the severe atypical subtype and exhibited more transitions,
      particularly with respect to the severe typical subtype. In contrast, males
      displayed more stable subtypes. The stable severe atypical subtype was associated
      with comorbid eating disorders as well as psychosis syndromes, whereas the stable
      severe typical subtype was associated only with psychosis syndromes. Our results
      provide first evidence for the notion that long-term stability and transition
      patterns differ by sex and depression subtypes. This finding has received too
      little attention in previous research and should be considered in treatments.

PMID- 24292329
TI  - Simulation and evaluation of a bone sawing procedure for orthognathic surgery
      based on an experimental force model.
AB  - Bone sawing is widely used in orthognathic surgery to correct maxillary
      deformities. Successful execution of bone sawing requires a high level of
      dexterity and experience. A virtual reality (VR) surgical simulator can provide a
      safe, cost-effective, and repeatable training method. In this study, we developed
      a VR training simulator with haptic functions to simulate bone-sawing force,
      which was generated by the experimental force model. Ten human skulls were
      obtained in this study for the determination of surgical bone-sawing force. Using
      a 5-DOF machining center and a micro-reciprocating saw, bone specimens with
      different bone density were sawed at different feed rates (20, 40, and 60 mm/min)
      and spindle speeds (9800, 11,200 and 12,600 cycles per minute). The sawing forces
      were recorded with a piezoelectric dynamometer and a signal acquisition system.
      Linear correlation analysis of all experimental data indicates that there were
      significant positive linear correlations between bone-sawing force and bone
      density and tool feed rate and a moderate negative linear correlation with tool
      spindle rate. By performing multiple regression analysis, the prediction models
      for the bone-sawing procedure were determined. By employing Omega.6 as a haptic
      device, a medical simulator for the Lefort I osteotomy was developed based on an
      experimental force model. Comparison of the force-time curve acquired through
      experiments and the curve computed from the simulator indicate that the obtained
      forces based on the experimental force model and the acquired data had the same
      trend for the bone-sawing procedure of orthognathic surgery. 

PMID- 24292328
TI  - The protective role of Bax inhibitor-1 against chronic mild stress through the
      inhibition of monoamine oxidase A.
AB  - The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis
      linked to endoplasmic reticulum (ER) stress. It has been hypothesized that BI-1
      protects against neuron degenerative diseases. In this study, BI-1-/- mice showed
      increased vulnerability to chronic mild stress accompanied by alterations in the
      size and morphology of the hippocampi, enhanced ROS accumulation and an ER stress
      response compared with BI-1+/+ mice. BI-1-/- mice exposed to chronic mild stress
      showed significant activation of monoamine oxidase A (MAO-A), but not MAO-B,
      compared with BI-1+/+ mice. To examine the involvement of BI-1 in the Ca2+
      sensitive MAO activity, thapsigargin-induced Ca2+ release and MAO activity were
      analyzed in neuronal cells overexpressing BI-1. The in vitro study showed that BI
      1 regulates Ca2+ release and related MAO-A activity. This study indicates an
      endogenous protective role of BI-1 under conditions of chronic mild stress that
      is primarily mediated through Ca2+-associated MAO-A regulation.

PMID- 24292330
TI  - New insights into small molecule activation by acyclic silylenes: a computational
      investigation.
AB  - Recently synthesized acyclic silylenes have the potential to rival transition
      metal complexes in performing single site small molecule activation, which is
      significant because of the need to find cheap and green alternatives to
      transition metal complexes for this important class of reactions. However, the
      current computational study, a full quantum chemical investigation with density
      functional theory, demonstrates that undesired side reactions would be
      competitive in these systems during small molecule activation. The current
      investigation, in addition to shedding light on this problem, also provides
      solutions on how the undesired side reactions during small molecule activation
      can be avoided. 

PMID- 24292332
TI  - Controlled colloidal synthesis of iron pyrite FeS2 nanorods and quasi-cubic
      nanocrystal agglomerates.
AB  - Earth-abundant and nontoxic pyrite iron disulfide (FeS2) is very promising for
      photovoltaic applications but the phase purity and the morphology of iron pyrite
      nanocrystals (NCs) have a significant impact on the solar cell performance. In
      this work, we systematically investigated reaction conditions and the local
      chemical environment on the phase purity and morphology of iron pyrite NCs
      synthesized via the hot injection method. By using different solvents to dissolve
      iron and sulfur agents, varying reactant concentrations, and adding
      trioctylphosphine oxide (TOPO) or 1,2-hexadecanediol (Diol) into the reaction
      solution, iron pyrite short, branched and chromosome-like rods were obtained with
      a diameter of ~10 nm and a length of ~20-30 nm as well as quasi-cubic NC
      agglomerates with a size of ~200 nm. Our experimental results show that the molar
      ratio of sulfur to iron and the reaction temperature are two critical factors in
      determining the crystalline phase of the synthesized materials. A mechanism
      involving the generation of H2S is proposed to explain the phase purity observed.
      The as-synthesized iron pyrite NCs can be dispersed well in chloroform,
      chlorobenzene, toluene, and hexane and thus are promising in solution-processable
      photovoltaic applications.

PMID- 24292331
TI  - Identification of rat respiratory mucosa stem cells and comparison of the early
      neural differentiation potential with the bone marrow mesenchymal stem cells in
      vitro.
AB  - The aim of this study is to identify rat nasal septum respiratory mucosa-derived
      mesenchyme stem cells (RM-MSCs) and to compare its neural lineage differentiation
      capacity with bone marrow-derived mesenchyme stem cells (BM-MSCs) after a short
      period of neural induction culture in vitro. The cell morphology was observed
      with light microscopy; cell proliferation was assessed by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide (MTT). The characteristics of the cells
      were evaluated with flow cytometry, immunofluorescence, real-time quantitative
      PCR (RT-PCR), and Western blotting. The results showed that rat nasal respiratory
      mucosa contains RM-MSCs that exhibited similar proliferation rate as BM-MSCs in
      vitro. Both RT-PCR and Western blotting analyses demonstrated that RM-MSCs showed
      higher expression of neural lineage markers than BM-MSCs after a short period of
      neural induction culture, and secreted higher level of brain-derived neurotrophic
      factor. RM-MSCs were more amenable to differentiate into neural or glial cell
      after a short period of neural induction culture than BM-MSCs in vitro; and it
      could be considered as another optimal source of stem cells for cell-based
      therapy to neurological diseases. 

PMID- 24292333
TI  - Subcellular localization of Mdm2 expression and prognosis of breast cancer.
AB  - BACKGROUND: Mouse double minute 2 (Mdm2) is a negative regulator of the tumor
      suppressor p53. The p53-Mdm2 pathway may play a role in cancer development and
      prognosis, although the role of p53-Mdm2 in breast cancer remains unclear.
      METHODS: p53 and Mdm2 expressions were determined by immunohistochemistry of
      tissue microarrays of 865 breast cancer patients who underwent surgery.
      Clinicopathological characteristics and survival data were analyzed. Mdm2
      expression was categorized into four groups: negative, cytoplasm positive,
      nucleus positive, and concurrent nuclear and cytoplasm positive (N+&C+). RESULTS:
      Negative, cytoplasm-positive, nucleus-positive, and N+&C+ expressions of Mdm2
      were observed in 59.2, 10.9, 27.8, and 2.1 % of patients, respectively. The N+&C+
      group was associated with larger tumor size, higher grade, negativity for
      estrogen and progesterone receptors, HER2 positivity, high Ki-67 index, p53
      positivity, and triple negative breast cancer. p53-positive tumors showed poorer
      overall survival than p53-negative tumors. The nucleus-positive and N+&C+ groups
      showed poorer disease-free survival than the negative and cytoplasm-positive
      groups. In multivariate analysis, nuclear Mdm2 expression including the N+&C+
      group was significantly related to poor prognosis. CONCLUSIONS: Concurrent
      nuclear and cytoplasmic Mdm2 expression was an independent prognostic factor in
      patients with breast cancer. Subcellular localization of Mdm2 expression should
      be considered in the evaluation of Mdm2 in breast cancer.

PMID- 24292335
TI  - Multi-orbital cluster perturbation theory for transition metal oxides.
AB  - We present an extension of cluster perturbation theory to include many-body
      correlations associated with local e-e repulsion in real materials. We show that
      this approach can describe the physics of complex correlated materials where
      different atomic species and different orbitals coexist. The prototypical case of
      MnO is considered. 

PMID- 24292336
TI  - A proton channel allows a hydrogen oxidation catalyst to operate at a moderate
      overpotential with water acting as a base.
AB  - We report the incorporation of a simple enzyme-inspired proton channel onto a
      hydrogen oxidation catalyst. This modification facilitates proton transfer and
      lowers the overpotential for oxidation of H2 by 300 mV when using water as a
      base. 

PMID- 24292334
TI  - Prevalence and risk factors of bone metastasis and skeletal related events in
      patients with primary breast cancer in Japan.
AB  - BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of
      breast cancer. It often causes skeletal-related events (SREs) that worsen quality
      of life. We investigated the prevalence and risk factors for BM and SRE using a
      dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND
      METHODS: We collected data on primary breast cancer patients with node-positive
      or node-negative disease at intermediate to high risk of recurrence. The risk
      factors affecting the BM-free rate, SRE-free rate and overall survival were
      analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779
      patients who were diagnosed with breast cancer during 2003-2005 were collected
      from the BORN and 1,708 cases were used for analysis. The median follow-up
      duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate
      at 5 years was 89.2 %. The annual hazard ratio of BM development differs
      remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of
      193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate
      analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P =
      0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038)
      were independently significant risk factors for BM-free rate, but only clinical
      stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly
      correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies
      the prevalence and risk factors for BM and SRE in Japanese breast cancer
      patients. Our results show the importance of considering subtype in the care of
      BM and SRE.

PMID- 24292337
TI  - Rational design and synthesis of novel dibenzo[b,d]furan-1,2,3-triazole
      conjugates as potent inhibitors of Mycobacterium tuberculosis.
AB  - A series of novel dibenzo[b,d]furan-1,2,3-triazole conjugates, rationally
      designed by reorientation of dibenzo[b,d]furan pharmacophore and alkyl/aryl
      groups appended on 1,2,3-triazole core, were synthesized using click chemistry.
      The required key intermediate, 2-ethynyl dibenzo[b,d]furan 3 was prepared from
      dibenzofuran-2-carboxaldehyde using Corey-Fuchs reaction. Further reaction of 3
      with various alkyl/aryl azides in the presence of copper catalyst produced 1,2,3
      triazole conjugates in excellent yields. Evaluation of all the new compounds for
      in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv
      (ATCC27294), resulted 5a (MIC: 1.56 MUg/mL), 5d (MIC: 0.78 MUg/mL) and 5f (MIC:
      0.78 MUg/mL) as promising lead analogues. Among these three compounds, 1-(4
      bromobenzyl)-4-(dibenzo[b,d]furan-2-yl)-1H-1,2,3-triazole (5f) emerged as the
      most promising antitubercular agent with lowest cytotoxicity (selectivity index:
      ?25) against the HEK-293T cell line.

PMID- 24292338
TI  - 2-(1H-Pyrazol-1-yl)acetic acids as chemoattractant receptor-homologous molecule
      expressed on Th2 lymphocytes (CRTh2) antagonists.
AB  - In this manuscript, the synthesis and biological activity of a series of pyrazole
      acetic acid derivatives as CRTh2 antagonists is presented. Biological evaluation
      in vitro revealed that the pyrazole core showed in several cases a different
      structure-activity relationship (SAR) to that of related indole acetic acid. A
      potent series of ortho-sulfonyl benzyl substituents was found, from which
      compounds 27 and 63 were advanced to in vivo profiling.

PMID- 24292339
TI  - Design, synthesis, molecular docking and 3D-QSAR studies of potent inhibitors of
      enoyl-acyl carrier protein reductase as potential antimycobacterial agents.
AB  - In order to develop a lead antimycobacterium tuberculosis compound, a series of
      52, novel pyrrole hydrazine derivatives have been synthesized and screened which
      target the essential enoyl-ACP reductase. The binding mode of the compounds at
      the active site of enoyl-ACP reductase was explored using surflex-docking method.
      The binding model suggests one or two hydrogen bonding interactions between
      pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 MUg/mL)
      showed hydrogen bonding interactions with Tyr158 and NAD(+) in the same manner as
      those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with
      database alignment were the best in terms of overall statistics. The predictive
      ability of the CoMFA and CoMSIA models was determined using a test set of 13
      compounds, which gave predictive correlation coefficients (r(pred)(2)) of 0.896
      and 0.930, respectively.

PMID- 24292340
TI  - Double gamma-alkylation of allylic phosphorus ylides: a unique access to oxa
      bicyclic[3.3.0] diene skeletons.
AB  - A new ylide-initiated tandem cyclization reaction based on gamma-dialkylation of
      allylic ylides has been realized, delivering a series of [3.3.0] oxa-bicyclic
      dienes in high yields with perfect diastereoselectivity. 

PMID- 24292341
TI  - Sleep problems and depression in adolescence: results from a large population
      based study of Norwegian adolescents aged 16-18 years.
AB  - Both sleep problems and depression are common problems in adolescence, but well
      defined large epidemiological studies on the relationship are missing in this age
      group. The aim of this study was to examine the association between depression
      and several sleep parameters, including insomnia, in a population-based study of
      adolescents aged 16-18 years, and to explore potential gender differences. A
      large population-based study in Hordaland County in Norway conducted in 2012, the
      ung@hordaland study, surveyed 10,220 adolescents aged 16-18 years (54% girls)
      about sleep and depression. The sleep assessment included measures of the basic
      sleep parameters for weekdays and weekends. Depression was defined as scoring
      above the 90th percentile on the total score of Short Moods and Feelings
      Questionnaire (SMFQ). There was a large overlap between insomnia and depression
      in both genders and across depressive symptoms. Depressed adolescents exhibited
      significantly shorter sleep duration and time in bed as well as significantly
      longer sleep onset latency (SOL) and wake after sleep onset (WASO). Adolescents
      with insomnia had a 4- to 5-fold increased odds of depression compared to good
      sleepers. There was also a significant interaction between insomnia, sleep
      duration and depression, with a more than eightfold increase in odds of
      depression for those who met criteria for insomnia and who slept <6 h. These
      associations held for both genders, but were stronger in boys. To the best of our
      knowledge, this is the first population-based study to investigate sleep and
      insomnia in relation to depression among adolescents. The findings call for
      increased awareness of sleep problems and depression as a major public health
      issue.

PMID- 24292342
TI  - Relationship between alcohol dependence, escape drinking, and early neural
      attention to alcohol-related cues.
AB  - RATIONALE: Previous work has indicated that implicit attentional biases to
      alcohol-related cues are indicative of susceptibility to alcohol dependence and
      escape drinking, or drinking to avoid dysphoric mood or emotions. OBJECTIVE: The
      goal of the current study was to examine whether alcohol dependence and escape
      drinking were associated with early neural attentional biases to alcohol cues.
      METHODS: Electroencephalography data were recorded from 54 college students who
      reported that they regularly drank alcohol, while they viewed alcohol and control
      pictures that contained human content (active) or no human content (inactive).
      RESULTS: Those who were alcohol dependent showed more neural attentional bias to
      the active alcohol-related stimuli than to the matched control stimuli early in
      processing, as indicated by N1 amplitude. Escape drinkers showed greater neural
      attention to the active alcohol cues than non-escape drinkers, as measured by
      larger N2 amplitudes. CONCLUSIONS: While alcohol dependence is associated with
      enhanced automatic attentional biases early in processing, escape drinking is
      associated with more controlled attentional biases to active alcohol cues during
      a relatively later stage in processing. These findings reveal important
      information about the time-course of attentional processing in problem drinkers
      and have important implications for addiction models and treatment.

PMID- 24292344
TI  - Combined traumatic atlantooccipital and atlantoaxial articulation instability: a
      case report with survival.
AB  - Traumatic atlantooccipital dislocation is a rare injury in survivors with 15 %
      share in deaths due to spinal injury. The authors present a case of a patient
      with concurrent atlantooccipital and atlantoaxial instability of the upper
      cervical spine, which he suffered after a fall from height. Atlantooccipital
      dislocation in surviving patients is a rare injury, for which in some cases
      coincident bone injury is reported to upper cervical spine, such as occipital
      fracture or contingent odontoid (C2 dens) fracture. In our case, it is combined
      with atlantoaxial instability and this combined type of injury has not yet been
      described in the literature. We performed realignment of the dislocation and
      posterior occipitocervical (C0-C3) fusion. After the surgery, the patient
      manifested neurological improvement almost to a normal neurological outcome with
      persistent residual finding after subarachnoid hemorrhage.

PMID- 24292345
TI  - Spinal canal morphology and clinical outcomes of microsurgical bilateral
      decompression via a unilateral approach for lumbar spinal canal stenosis.
AB  - PURPOSE: Microsurgical bilateral decompression via a unilateral approach for
      lumbar spinal stenosis is a less invasive technique compared to conventional
      laminectomy. Although many technical reports have demonstrated acceptable overall
      surgical outcomes for this approach, no studies have attempted to clarify the
      clinical outcomes thereof in regard to anatomical variance of the spinal canal.
      This study was conducted to analyze the clinical outcomes of microsurgical
      bilateral decompression via a unilateral approach according to spinal canal
      morphology in degenerative lumbar spinal stenosis. METHODS: Between January 2008
      and December 2009, 144 patients with single-level spinal lumbar stenosis
      underwent microsurgical bilateral decompression via a unilateral approach by a
      single surgeon. Patients were categorized into three groups according to spinal
      canal shape: round (n = 42), oval (n = 36), and trefoil (n = 66), and clinical
      parameters were assessed both before and after surgery with 2-3 years of follow
      up. RESULTS: Mean visual analog scale (VAS) and Oswestry disability index (ODI)
      decreased after surgery, respectively, from 8.1 and 59.8 % to 2.1 and 19.1 % in
      the round shaped spinal canal group, from 7.2 and 47.1 % to 2.2 and 15.1 % in the
      oval shaped spinal canal group, and from 6.8 and 53.6 % to 3.6 and 33.3 % in the
      trefoil shaped spinal canal group. In all groups, VAS and ODI scores
      significantly improved postoperatively (p < 0.01), although less improved VAS and
      ODI scores were observed in the trefoil shaped spinal canal group (p < 0.01). The
      overall patient satisfaction rate was 66.7 %; however, statistically significant
      lower satisfaction rates were reported in the trefoil shaped spinal canal group
      (p < 0.01). CONCLUSIONS: Microsurgical bilateral decompression via a unilateral
      approach may be a good modality for treating round or oval shape spinal canal
      stenosis, but is not recommended for trefoil-shaped-stenosis. The current authors
      recommend performing the bilateral decompression technique in cases of trefoil
      shaped-spinal canal stenosis.

PMID- 24292346
TI  - Sodium thiosulphate treatment of uraemic tumoral calcinosis.
AB  - OBJECTIVE: The objective of this study was to describe the efficacy of sodium
      thiosulphate (STS) in tumoral calcinosis (TC). METHODS: The methodology involved
      the reporting of four retrospective case reports of TC complicating end-stage
      renal disease (ESRD). RESULTS: We investigated STS treatment in four patients
      (two men; ages 46-70 years) with TC. ESRD was secondary to nephronophthisis (n =
      1), membranoproliferative glomerulonephritis (n = 1), diabetic nephropathy (n =
      1), and thrombotic microangiopathy (n = 1). TC developed 3-28 years after
      dialysis began and resulted in articular pain (n = 4) and stiffness (n = 1). It
      involved shoulders and hips and was diffuse in one patient. Several treatments
      were tried without success. STS 12.5-25 g was given intravenously after each
      dialysis session for 11-14 months. Pain and stiffness rapidly disappeared and TC
      showed partial or total regression. Side effects during infusion included
      increased blood pressure (n = 1), nausea (n = 1) and vomiting (n = 1). TC did not
      recur after treatment discontinuation with follow-up of 1.5-12 years. CONCLUSION:
      STS showed promising efficacy in this short series of TC. Further studies are
      warranted.

PMID- 24292347
TI  - Osteoarthritis of the knee: multicompartmental or compartmental disease?
AB  - OBJECTIVE: Knee OA has been conceptualized as a multicompartmental disease, as a
      compartmental disease or as a combination of these two disease processes. The aim
      of this study was to determine the associations between four radiographic
      features (joint space narrowing, osteophyte formation, sclerosis and cysts)
      across and within the three knee compartments (medial tibiofemoral, lateral
      tibiofemoral and patellofemoral compartment) in knee OA. METHODS: Data from the
      Amsterdam OA Cohort were used. In 298 patients diagnosed with knee OA,
      radiographic features were examined in three knee joint compartments.
      Radiographic features were scored according to standardized scoring methods.
      Factor analysis was used to examine associations between the four radiographic
      features across and within compartments. RESULTS: A bifactor model showed a
      general multicompartmental factor: 10 of 12 radiographic features across the
      entire joint were associated with the general factor. The bifactor model also
      showed three compartmental factors-one for each compartment: joint space
      narrowing, sclerosis and to a lesser extent osteophyte formation were associated
      with these compartmental factors. CONCLUSION: These findings suggest a
      multicompartmental disease process in the knee, characterized by associations
      among features across the entire joint, as well as compartmental disease
      processes in each knee compartment, characterized by associations among features
      within specific compartments. Longitudinal studies are needed to explore the
      possibility of the development from a compartmental disease to a
      multicompartmental disease and the impact of contributing factors on the
      development.

PMID- 24292348
TI  - Essential oil from Artemisia phaeolepis: chemical composition and antimicrobial
      activities.
AB  - Artemisia phaeolepis, a perennial herb with a strong volatile odor, grows on the
      grasslands of Mediterranean region. Essential oil obtained from Artemisia
      phaeolepis was analyzed by gas chromatography-flame ionization detection and gas
      chromatography-mass spectrometry. A total of 79 components representing 98.19% of
      the total oil were identified, and the main compounds in the oil were found to be
      eucalyptol (11.30%), camphor (8.21%), terpine-4-ol (7.32%), germacrene D (6.39),
      caryophyllene oxide (6.34%), and caryophyllene (5.37%). The essential oil showed
      definite inhibitory activity against 10 strains of test microorganisms.
      Eucalyptol, camphor, terpine-4-ol, caryophyllene, germacrene D and caryophyllene
      oxide were also examined as the major components of the oil. Camphor showed the
      strongest antimicrobial activity; terpine-4-ol, eucalyptol, caryophyllene and
      germacrene D were moderately active and caryophyllene oxide was weakly active.
      The study revealed that the antimicrobial properties of the essential oil can be
      attributed to the synergistic effects of its diverse major and minor components. 

PMID- 24292349
TI  - Effect of storage on refined olive oil composition: stabilization by addition of
      chlorophyll pigments and squalene.
AB  - Refined olive oil has been analyzed in order to evaluate the influence of storage
      time on their quality after enrichment with chlorophyll pigments and squalene. At
      the end of the storage, chlorophyll pigments decomposed for more than 90%, while,
      carotene pigment loss was lower showing up to 75% in all oil samples stored at 20
      degrees C and 50 degrees C. The reduction of total phenolic compounds exhibited
      similar degradation profiles, reducing by 81% for enriched refined olive oil
      stored at 20 degrees C and 50 degrees C after six months. For all studied
      samples, squalene content decreased significantly (p< 0.05) only after four
      months of storage. Oils with added pure squalene had the lower peroxide values
      (52 meq O2 . kg(-1)) at the end of storage at 20 degrees C. After six months of
      storage the oxidative stability increased to 1 h 28 min and 2 h 06 min for
      refined olive oil stored at 20 degrees C enriched with chlorophyll + squalene and
      only by squalene, respectively. Therefore, squalene supplemented with 800 mg .
      kg(-1) exhibited favorable antioxidant effects and is preferable for effectively
      avoiding oxidation. This study could provide useful information for industry to
      produce high-stability vegetable oil. 

PMID- 24292350
TI  - Oxygen content and oxidation in frying oil.
AB  - The relation between oxygen content and oxidation was investigated in frying
      oils. When canola oil, a canola-soybean oil blend or a trioctanoylglycerol
      (glycerol tricaprate) sample were heated with stirring, their dissolved oxygen
      content decreased abruptly at about 120 degrees C and the carbonyl values (CV)
      increased gradually with heating and reached values of 6-7 at 180 degrees C in
      the blended and canola oils, while the CV of trioctanoylglycerol was zero up to
      150 degrees C. Probably this abrupt decrease in oxygen content above 120 degrees
      C can be attributed to the solubility of oxygen in oil rather than because of
      oxidative reactions. The oxygen content of oil that has been stripped of part of
      its oxygen, increased at temperatures between 25 and 120 degrees C. In oils that
      have lost their oxygen by being heated to 180 degrees C, standing at room
      temperature will slowly restore their oxygen content as the oil cools.
      Intermittent simple heating of oil promoted oxygen absorbance during cooling
      periods and standing times, and it resulted in an elevated content of polar
      compounds (PC). Domestic deep-frying conditions also favor the presence of oxygen
      in oil below 120 degrees C and during the oil's long standing at room
      temperature. The oxygen content in oil was low during deep-frying, but oxidation
      was active at the oil/air interface of bubbles generated by foods being fried.
      Repeated use of oil at temperatures between 25-180 degrees C resulted in oil with
      low oxygen values. 

PMID- 24292351
TI  - Consumption of a structured triacylglycerol containing behenic and oleic acids
      increases fecal fat excretion in humans.
AB  - We examined the fecal fat excretion of mildly hypertriacylglycerolemic subjects
      who ingested soft cookies containing 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol
      (BOO) for 7 days. The subjects included 14 healthy men (average age; 44.9 +/-
      1.7) whose fasting plasma triacylglycerol level ranged from 150 to 250 mg/dL.
      Every day for 7 days, the subjects ate 5 soft cookies containing margarine with
      the BOO-rich experimental oil (BOO intake, 2.46 g/day). The placebo group ate
      soft cookies containing margarine without BOO. This study was a randomized double
      blind, placebo-controlled, crossover study. Feces were collected for 3 days prior
      to the end of the treatment period, and fecal fat and fatty acid composition were
      determined. The fecal wet weight was significantly increased in BOO group
      compared with that in the placebo group. Moreover, fecal fat and fatty acid level
      were significantly higher in the BOO group than in the placebo group. There were
      no significant differences in the fecal fatty acid composition of the BOO and
      placebo groups. These results suggest that dietary BOO increases fecal excretion
      of dietary fat in humans. However, BOO does not increase the excretion of
      specific fatty acids; it increases the excretion of all fatty acids of dietary
      origin, which may lead to lower and delay intestinal absorption of dietary fat. 

PMID- 24292352
TI  - Effect of droplet size on autoxidation rates of methyl linoleate and alpha
      linolenate in an oil-in-water emulsion.
AB  - Methyl linoleate and alpha-linolenate were used as representative n-6 and n-3
      polyunsaturated fatty acid esters, respectively, to examine the effect of oil
      droplet size on autoxidative stability in oil-in-water systems. The emulsions,
      which were prepared via membrane emulsification and had a mean oil droplet size
      of approximately 1-30 MUm, and had a stable size during the autoxidation of each
      substrate at 55 degrees C. The autoxidation of methyl linoleate did not depend on
      oil droplet size during the entire process and that of methyl alpha-linolenate
      was independent of oil droplet size during the first half of the autoxidation
      process. However, the autoxidation rate of methyl alpha-linolenate proceeded
      faster in the emulsion with smaller oil droplet size during the last half of the
      autoxidation process. 

PMID- 24292353
TI  - Actual ratios of triacylglycerol positional isomers and enantiomers comprising
      saturated fatty acids and highly unsaturated fatty acids in fishes and marine
      mammals.
AB  - It has been previously shown that the positional isomers of triacylglycerol (TAG)
      containing palmitic acid (P) and highly unsaturated fatty acids (HUFAs) such as
      DHA (D) and EPA (E) vary between fishes and marine mammals. However, it has not
      yet been understood why in marine mammals HUFAs are located only at the alpha
      position when two palmitic acid chains combine, and not in fishes. In order to
      gain further understanding of the biosynthetic pathways involved in the formation
      of these asymmetric TAGs, we investigated whether the HUFA in the TAG of marine
      mammals exists predominantly at the sn-1 or sn-3 position. We examined the TAG
      positional isomers and enantiomers in marine organisms in detail. As a result,
      while PDP and PEP were not detected, sn-PPD and sn-PPE were found in abundance in
      marine mammals. For fishes, on the other hand, PDP, PEP, sn-PPD, and sn-PPE were
      all identified. In the case of TAGs that contain two HUFAs and one palmitic acid,
      marine mammals were rich in DPD and EPE whereas fishes were rich in sn-PDD and sn
      PEE. 

PMID- 24292354
TI  - Interfacial properties in Langmuir monolayers and LB films of DPPC with partially
      fluorinated alcohol (F8H7OH).
AB  - Two-component interactions between (perfluorooctyl) heptanol (F8H7OH) and
      dipalmitoylphosphatidylcholine (DPPC), which is a major component of pulmonary
      surfactants in mammals, were systematically elucidated using Langmuir monolayers
      and Langmuir-Blodgett (LB) films of the compounds. The interactions such as the
      miscibility of the compounds and their phase behavior were examined from
      thermodynamic and morphological perspectives. The surface pressure (pi)-molecular
      area (A) and surface potential (DeltaV)-A isotherms of the binary monolayers
      containing F8H7OH in different mole fractions (XF8H7OH) were measured
      simultaneously. The excess Gibbs free energy of mixing of the two components was
      calculated from the pi-A isotherms. The resulting isotherm data were employed to
      construct a two-dimensional (2D) phase diagram of the system. The phase diagram
      revealed that the transition pressure as well as the monolayer collapse pressure
      change with changes in XF8H7OH. These thermodynamic analyses suggested that the
      miscibility of the two components and the solidification of DPPC monolayers can
      be induced by the addition of F8H7OH. The phase behavior upon monolayer
      compression was observed morphologically in situ using Brewster angle microscopy
      (BAM) and fluorescence microscopy (FM), as well as ex situ using atomic force
      microscopy (AFM). Interestingly, the AFM-based analysis revealed the formation of
      monodispersed 2D micelles consisting of F8H7OH at low surface pressures. 

PMID- 24292355
TI  - Two-component Langmuir monolayers and LB films of DPPC with partially fluorinated
      alcohol (F8H9OH).
AB  - The interaction of (perfluorooctyl)nonanol (F8H9OH) with
      dipalmitoylphosphatidylcholine (DPPC) was systematically studied in two-component
      monolayers at air-water interface. The thermodynamic property and phase
      morphology of the monolayers were investigated by isotherm measurements and
      several microscopic methods such as Brewster angle microscopy, fluorescence
      microscopy, and atomic force microscopy (AFM). The AFM topographies for Langmuir
      Blodgett films of F8H9OH exhibit the formation of monodispersed surface micelles.
      In the two-component system, the incorporation of F8H9OH induces condensation (or
      solidification) of DPPC monolayers. The excess Gibbs free energy and interaction
      parameter (or energy) of the two components were calculated from the isotherm
      data. Both the phase transition pressure for the coexistence of ordered and
      disordered phases and collapse pressure of monolayers vary with the mole fraction
      of F8H9OH, indicating binary miscibility between F8H9OH and DPPC within a
      monolayer state. The miscibility is also confirmed visually by in situ and ex
      situ microscopy at micro- and nanometer scales. 

PMID- 24292356
TI  - Calorimetric study of micelle formation of sodium alkyl sulfates in water.
AB  - Calorimetric measurements were conducted on aqueous solutions of sodium alkyl
      sulfates (SCnS; H(CH2)nOSO3Na, n = 5-13) at 298.15 K. The solute partial molar
      enthalpy, H(s), was evaluated referred to infinitely diluted state and compared
      for the SCnS homologues. At low concentrations, the H(s) increased with the
      molality m until the critical micelle concentration (CMC) was reached. In the
      concentration range between the CMC and about three times the CMC, the Hs
      decreased with increasing log m: H(s) = (17.9 - 1.8 n) - 14/(n-4.6) log m. The Hs
      observed at the CMC was taken as the enthalpy of micelle formation, DeltaH(m),
      which was expressed as DeltaH(m) / kJ mol(-1) = 21.3 - 1.7 n for SCnS with n from
      7 to 13. The Gibbs energy of micelle formation, DeltaG(m), was estimated from the
      CMC values: DeltaG(m) / kJ mol(-1) = 0.2 - 3.1 n. The entropy of micelle
      formation, DeltaS(m), was calculated as TDeltaS(m) / kJ mol(-1) = 21.1 + 1.4 n.
      The large positive entropy term was the driving force for micelle formation. An
      attempt was also made to calculate the concentration dependence of Hs for SDS
      (SC12S) from the concentrations and the apparent molar enthalpies estimated for
      the sodium ion, dodecyl sulfate ion, and the micelles.

PMID- 24292357
TI  - Effect of dietary Maitake (Grifola frondosa) mushrooms on plasma cholesterol and
      hepatic gene expression in cholesterol-fed mice.
AB  - To investigate the effects of dietary Grifola frondosa on cholesterol, normal
      mice were fed a diet containing 1% cholesterol (HC group) or 1% cholesterol and
      10% freeze-dried G. frondosa powder (HC+G group) for 4 weeks and hepatic and
      plasma lipid levels were compared with those of a cholesterol-free diet-fed mice
      (N group). Hepatic total cholesterol (TC), triacylglycerol contents were
      considerably increased and plasma TC / phospholipid (PL) was also increased
      significantly in the HC group compared with the N group. However, plasma TC
      content decreased in the HC+G group compared with the HC group. To characterize
      the mechanisms responsible for lowered plasma cholesterol in G. frondosa
      supplemented mice, hepatic gene expression was profiled using DNA microarray and
      gene ontology. Genome analyses revealed that de novo cholesterol synthesis genes
      were suppressed following cholesterol intake. However, expression of bile acid
      biosynthesis and low-density lipoprotein receptor genes showed little change.
      Scarb1, Abcg5, and Abcg8, involved in cholesterol transport and excretion, were
      slightly upregulated in the HC+G group compared with the HC group. These data
      indicate the plasma cholesterol-lowering effect of G. frondosa. Moreover, fatty
      acid (FA) beta-oxidation was promoted via adipocytokine signaling pathways, and
      Saa, encodes serum amyloid A related to arteriosclerosis, was suppressed in the
      HC+G group. 

PMID- 24292358
TI  - Structure-property studies of thermoplastic and thermosetting polyurethanes using
      palm and soya oils-based polyols.
AB  - Palm and soya oils were converted to monoglycerides via transesterification of
      triglycerides with glycerol by one step process to produce renewable polyols.
      Thermoplastic polyurethanes (TPPUs) were prepared from the reaction of the
      monoglycerides which act as polyol with 4,4'-methylenediphenyldiisocyanate (MDI)
      whereas, thermosetting polyurethanes (TSPUs) were prepared from the reaction of
      glycerol, MDI and monoglycerides in one pot. Characterization of the
      polyurethanes was carried out by FT-IR, (1)H NMR, and iodine value and sol-gel
      fraction. The TSPUs showed good thermal properties compared to TPPUs as well as
      TSPUs exhibits good properties in pencil hardness and adhesion, however poorer in
      flexural and impact strength compared to TPPUs. The higher percentage of cross
      linked fraction, the higher degree of cross linking occurred, which is due to the
      higher number of double bond presents in the TSPUs. These were reflected in
      iodine value test as the highest iodine value of the soya-based thermosetting
      polyurethanes confirmed the highest degree of cross linking. Polyurethanes based
      on soya oil showed better properties compared to palm oil. This study is a
      breakthrough development of polyurethane resins using palm and soya oils as one
      of the raw materials. 

PMID- 24292359
TI  - Nonionic reverse micelles near the critical point.
AB  - We report shape, size, and internal cross-sectional structure of diglycerol
      monomyristate (C14G2) reverse micelles in n-hexadecane near the critical point
      using small-angle X-ray scattering (SAXS). Pair-distance distribution function,
      p(r), which gives structural information in real-space, was obtained by indirect
      Fourier transformation (IFT) method. The p(r) showed a clear picture of rodlike
      micelles at higher temperatures well above the critical point (micellar solution
      phase separates into two immiscible liquids at ~ 48 degrees C). At a fixed
      surfactant concentration (5% C14G2), decrease in temperature increases the
      micellar size monotonously and surprisingly shape of the p(r) curve at 50 degrees
      C; close to the critical point, mimics the shape of the two dimensional disk-like
      micelles indicating the onset of critical fluctuations (attractive interactions
      among rodlike micelles forming a weak network). A similar behavior has been
      observed with normal micelles in aqueous system near the critical point. When the
      system is heated to 60 degrees C, shape of the p(r) curve regains rodlike
      structure. At fixed temperature of 60 degrees C, increase in C14G2 concentration
      induced one dimensional micellar growth. Maximum length of micelles increases
      from ca. 23.5 to 46.0 nm upon increasing concentration from 1 to 12% keeping
      cross section diameter apparently unchanged at ca. 4.0 nm.

PMID- 24292360
TI  - RNASurface: fast and accurate detection of locally optimal potentially structured
      RNA segments.
AB  - MOTIVATION: During the past decade, new classes of non-coding RNAs (ncRNAs) and
      their unexpected functions were discovered. Stable secondary structure is the key
      feature of many non-coding RNAs. Taking into account huge amounts of genomic
      data, development of computational methods to survey genomes for structured RNAs
      remains an actual problem, especially when homologous sequences are not available
      for comparative analysis. Existing programs scan genomes with a fixed window by
      efficiently constructing a matrix of RNA minimum free energies. A wide range of
      lengths of structured RNAs necessitates the use of many different window lengths
      that substantially increases the output size and computational efforts. RESULTS:
      In this article, we present an algorithm RNASurface to efficiently scan genomes
      by constructing a matrix of significance of RNA secondary structures and to
      identify all locally optimal structured RNA segments up to a predefined size.
      RNASurface significantly improves precision of identification of known ncRNA in
      Bacillus subtilis. AVAILABILITY AND IMPLEMENTATION: RNASurface C source code is
      available from http://bioinf.fbb.msu.ru/RNASurface/downloads.html.

PMID- 24292361
TI  - ABACUS: an entropy-based cumulative bivariate statistic robust to rare variants
      and different direction of genotype effect.
AB  - MOTIVATION: In the past years, both sequencing and microarray have been widely
      used to search for relations between genetic variations and predisposition to
      complex pathologies such as diabetes or neurological disorders. These studies,
      however, have been able to explain only a small fraction of disease heritability,
      possibly because complex pathologies cannot be referred to few dysfunctional
      genes, but are rather heterogeneous and multicausal, as a result of a combination
      of rare and common variants possibly impairing multiple regulatory pathways. Rare
      variants, though, are difficult to detect, especially when the effects of causal
      variants are in different directions, i.e. with protective and detrimental
      effects. RESULTS: Here, we propose ABACUS, an Algorithm based on a BivAriate
      CUmulative Statistic to identify single nucleotide polymorphisms (SNPs)
      significantly associated with a disease within predefined sets of SNPs such as
      pathways or genomic regions. ABACUS is robust to the concurrent presence of SNPs
      with protective and detrimental effects and of common and rare variants;
      moreover, it is powerful even when few SNPs in the SNP-set are associated with
      the phenotype. We assessed ABACUS performance on simulated and real data and
      compared it with three state-of-the-art methods. When ABACUS was applied to type
      1 and 2 diabetes data, besides observing a wide overlap with already known
      associations, we found a number of biologically sound pathways, which might shed
      light on diabetes mechanism and etiology. AVAILABILITY AND IMPLEMENTATION: ABACUS
      is available at http://www.dei.unipd.it/~dicamill/pagine/Software.html.

PMID- 24292362
TI  - Finding consistent disease subnetworks using PFSNet.
AB  - MOTIVATION: Microarray data analysis is often applied to characterize disease
      populations by identifying individual genes linked to the disease. In recent
      years, efforts have shifted to focus on sets of genes known to perform related
      biological functions (i.e. in the same pathways). Evaluating gene sets reduces
      the need to correct for false positives in multiple hypothesis testing. However,
      pathways are often large, and genes in the same pathway that do not contribute to
      the disease can cause a method to miss the pathway. In addition, large pathways
      may not give much insight to the cause of the disease. Moreover, when such a
      method is applied independently to two datasets of the same disease phenotypes,
      the two resulting lists of significant pathways often have low agreement.
      RESULTS: We present a powerful method, PFSNet, that identifies smaller parts of
      pathways (which we call subnetworks), and show that significant subnetworks (and
      the genes therein) discovered by PFSNet are up to 51% (64%) more consistent
      across independent datasets of the same disease phenotypes, even for datasets
      based on different platforms, than previously published methods. We further show
      that those methods which initially declared some large pathways to be
      insignificant would declare subnetworks detected by PFSNet in those large
      pathways to be significant, if they were given those subnetworks as input instead
      of the entire large pathways. AVAILABILITY:
      http://compbio.ddns.comp.nus.edu.sg:8080/pfsnet/

PMID- 24292364
TI  - Convergent and contingent community responses to grass source and dominance
      during prairie restoration across a longitudinal gradient.
AB  - Restoring prairie on formerly cultivated land begins by selecting propagule seed
      sources and the diversity of species to reintroduce. This study examined the
      effects of dominant grass propagule source (cultivar vs. non-cultivar) and sown
      propagule diversity (grass:forb sowing ratio) on plant community structure. Two
      field experiments were established in Kansas and Illinois consisting of identical
      split plot designs. Dominant grass source was assigned as the whole-plot factor,
      and sown dominance of grasses (five levels of seeded grass dominance) as the
      subplot factor. Species density, cover, and diversity were quantified for 5
      years. The effect of dominant grass source on the cover of focal grasses, sown
      species, and volunteer species was contingent upon location, with variation
      between dominant grass sources observed exclusively in Kansas. Species density
      and diversity showed regionally convergent patterns in response to dominant grass
      source. Contrary to our hypotheses, total species density and diversity were not
      lower in the presence of grass cultivars, the grass source we had predicted would
      be more competitive. Sown grass dominance effects on the cover of the focal grass
      species were contingent upon location resulting from establishment corresponding
      better to the assigned treatments in Illinois. All other cover groups showed
      regionally convergent patterns, with lower cover of volunteers and higher cover
      of sown forbs, diversity, and species density in the lowest sown grass dominance
      treatment in both sites. Thus, decisions regarding the diversity of propagules to
      reintroduce had more consequence for plant community structure than cultivar or
      non-cultivar source of dominant grasses.

PMID- 24292363
TI  - Comparative transcriptional and functional profiling defines conserved programs
      of intestinal DC differentiation in humans and mice.
AB  - Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in
      mice. Here we characterized human gut DC populations and defined their
      relationship to previously studied human and mouse DCs. CD103(+)Sirpalpha(-) DCs
      were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-)
      DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpalpha(+) DCs
      aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs
      and supported the induction of regulatory T cells. Both CD103(+) DC subsets
      induced the TH17 subset of helper T cells, while CD103(-)Sirpalpha(+) DCs induced
      the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed
      conserved transcriptional programs among CD103(+) DC subsets and identified a
      selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the
      specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs,
      respectively. Our results highlight evolutionarily conserved and divergent
      programming of intestinal DCs. 

PMID- 24292365
TI  - SNP genotyping allows an in-depth characterisation of the genome of sugarcane and
      other complex autopolyploids.
AB  - Many plant species of great economic value (e.g., potato, wheat, cotton, and
      sugarcane) are polyploids. Despite the essential roles of autopolyploid plants in
      human activities, our genetic understanding of these species is still poor.
      Recent progress in instrumentation and biochemical manipulation has led to the
      accumulation of an incredible amount of genomic data. In this study, we
      demonstrate for the first time a successful genetic analysis in a highly
      polyploid genome (sugarcane) by the quantitative analysis of single-nucleotide
      polymorphism (SNP) allelic dosage and the application of a new data analysis
      framework. This study provides a better understanding of autopolyploid genomic
      structure and is a sound basis for genetic studies. The proposed methods can be
      employed to analyse the genome of any autopolyploid and will permit the future
      development of high-quality genetic maps to assist in the assembly of reference
      genome sequences for polyploid species. 

PMID- 24292366
TI  - A method for predicting collagen fiber realignment in non-planar tissue surfaces
      as applied to glenohumeral capsule during clinically relevant deformation.
AB  - Previously developed experimental methods to characterize micro-structural tissue
      changes under planar mechanical loading may not be applicable for clinically
      relevant cases. Such limitation stems from the fact that soft tissues,
      represented by two-dimensional surfaces, generally do not undergo planar
      deformations in vivo. To address the problem, a method was developed to directly
      predict changes in the collagen fiber distribution of nonplanar tissue surfaces
      following 3D deformation. Assuming that the collagen fiber distribution was known
      in the un-deformed configuration via experimental methods, changes in the fiber
      distribution were predicted using 3D deformation. As this method was solely based
      on kinematics and did not require solving the stress balance equations, the
      computational efforts were much reduced. In other words, with the assumption of
      affine deformation, the deformed collagen fiber distribution was calculated using
      only the deformation gradient tensor (obtained via an in-plane convective
      curvilinear coordinate system) and the associated un-deformed collagen fiber
      distribution. The new method was then applied to the glenohumeral capsule during
      simulated clinical exams. To quantify deformation, positional markers were
      attached to the capsule and their 3D coordinates were recorded in the reference
      position and three clinically relevant joint positions. Our results showed that
      at 60deg of external rotation, the glenoid side of the posterior axillary pouch
      had significant changes in fiber distribution in comparison to the other sub
      regions. The larger degree of collagen fiber alignment on the glenoid side
      suggests that this region is more prone to injury. It also compares well with
      previous experimental and clinical studies indicating maximum principle strains
      to be greater on the glenoid compared to the humeral side. An advantage of the
      new method is that it can also be easily applied to map experimentally measured
      collagen fiber distribution (obtained via methods that require flattening of
      tissue) to their in vivo nonplanar configuration. Thus, the new method could be
      applied to many other nonplanar fibrous tissues such as the ocular shell, heart
      valves, and blood vessels. 

PMID- 24292368
TI  - [Phacomatoses].

PMID- 24292367
TI  - Antituberculosis treatment and hepatotoxicity in patients with chronic viral
      hepatitis.
AB  - BACKGROUND: Whether antituberculosis (anti-TB) treatment in patients with chronic
      viral hepatitis affects the incidence and onset time of drug-induced
      hepatotoxicity (DIH) is still controversial. The aim of this retrospective study
      was to find out whether chronic viral hepatitis affects the incidence and onset
      time of DIH. METHODS: All patients diagnosed with active TB and being treated at
      a tertiary referral hospital between 2002 and 2009 were identified from medical
      records, from which 553 patients were enrolled in the study. The incidence and
      onset of DIH in patients with and without chronic viral hepatitis (controls) were
      compared. RESULTS: The incidence of DIH was similar in patients with and without
      chronic hepatitis (8 % [32/392] vs. 7 % [11/161], P > 0.05). The incidence of
      transient liver function impairment (TLI) was significantly lower in controls
      than in chronic hepatitis patients (2 % [9/392] vs. 12 % [20/161], P < 0.001. The
      mean onset times of DIH in the control, hepatitis B virus (HBV), and hepatitis C
      virus (HCV) groups were not significantly different (40, 39, and 67 days,
      respectively, all P > 0.05). The mean onset times of TLI in the control, HBV, and
      HCV groups were significantly different (23, 48, and 68 days, respectively, all P
      < 0.05). CONCLUSIONS: Liver function impairment during anti-TB therapy in
      patients with chronic viral hepatitis was due to mostly TLI, with TLI occurring
      later than in controls. Chronic viral hepatitis had no significant effect on the
      incidence of DIH.

PMID- 24292369
TI  - [Sturge-Weber syndrome].
AB  - Sturge-Weber syndrome (SWS) is a rare congenital disease which affects the brain,
      the skin and the eyes. It is a sporadically occurring neurocutaneous syndrome
      affecting the intracerebral veins (venous angiomatosis). The frequency is
      estimated to be 1 in 50,000 births [1]. The main symptom is intracranial
      leptomeningeal angiomatosis which mostly affects the occipital and posterior
      parietal lobes and can occur unilaterally and also bilaterally. Facial cutaneous
      vascular alterations occur ipsilaterally in the form of port wine stains (nevus
      flammeus) which are normally found in the catchment area of the trigeminal branch
      VI. Other clinical symptoms associated with SWS are seizures, glaucoma,
      headaches, transient neurological stroke-like episodes and cognitive impairment.
      Neurological cortical symptoms often include hemiparesis, hemiatrophy and
      hemianopsia. 

PMID- 24292371
TI  - Newborn circumcision outcomes: are parents satisfied with the results?
AB  - BACKGROUND/PURPOSE: Although physician-reported complications following
      circumcision are very low, parental satisfaction is not well documented. This
      study examined parental opinions and compared these with those of the medical
      professional. METHODS: Physicians independently assessed complications and
      cosmetic outcome following the circumcision. Six weeks post-circumcision,
      parental report of complications, cosmetic outcome, and overall satisfaction were
      assessed. RESULTS: Newborn infants (n = 710) were prospectively recruited and
      underwent either a Gomco [n = 552 (78 %)] or Plastibell((r)) [n = 158 (22 %)]
      circumcision. Physician assessed complication rates were equivalent (Gomco 4.3 %
      versus Plastibell 5.1 %; p = 0.67), however, parental assessment found a much
      lower complication rate for Gomco 5.6 % versus Plastibell 12.0 % (p < 0.001).
      There was no difference between who performed the procedure nor between the
      techniques in regards to parental rating of overall satisfaction (excellent/good:
      Gomco 96.9 % versus Plastibell 95.6 %, p = 0.45). However, perceived post
      operative pain as scored by parents was significantly higher in patients
      undergoing Plastibell procedure (6.4 % too much pain) versus Gomco (2.7 %; p =
      0.05). Gomco accounted for 72.7 % of parental cosmetically unsatisfactory cases.
      CONCLUSIONS: Clinicians and parents differed considerably in terms of opinion of
      cosmetic outcome and occurrence of post-operative complications. This study
      emphasizes the need for clinicians to better understand and address parental
      concerns before and after circumcision.

PMID- 24292370
TI  - Changes in the levels of p-ERK, p-CREB, and c-fos in rat mesocorticolimbic
      dopaminergic system after morphine-induced conditioned place preference: the role
      of acute and subchronic stress.
AB  - ERK pathway plays a critical role in the cellular adaptive responses to
      environmental changes. Stressful conditions can induce the activation of activate
      ERK, and its downstream targets, CREB and c-fos, in neural cells. Exposure to
      opioids has the same effect. In this study, we investigated the effects of
      morphine-induced conditioned place preference (CPP) on p-ERK/ERK ratio, p
      CREB/CREB ratio and c-fos level in the mesocorticolimbic dopaminergic system
      including the nucleus accumbens (NAc), amygdala (AMY), striatum (Str), and
      prefrontal cortex (PFC).Our aim was to determine if acute and subchronic stress
      would affect these alterations. Male Wistar rats were divided into two saline-
      and morphine-treated groups. Each group contained of control, acute stress, and
      subchronic stress subgroups. The CPP procedure was performed for all of the rats.
      We dissected out the NAc, AMY, Str, and PFC regions and measured the mentioned
      ratios and c-fos level by Western blot analysis. The results revealed that in
      saline-treated animals, all factors enhanced significantly after performing acute
      and subchronic stress while there was an exception in p-ERK/ERK ratio in the Str
      and PFC; the changes were not significant during acute stress. Conditioning score
      decreased after applying the subchronic but not acute stress. In morphine-treated
      animals, all factors were increased after application of acute and subchronic
      stress, and conditioning scores also decreased after stress. Our findings suggest
      that in saline- or morphine-treated animals, acute and subchronic stress
      increases p-ERK, p-CREB, and c-fos levels in the mesocorticolimbic system. It has
      been shown that morphine induces the enhancement of the mentioned factors; on the
      other hand, our result demonstrates that stress can amplify these changes. 

PMID- 24292372
TI  - Organogallium- and organozinc-rich palladium and platinum clusters.
AB  - The heteroleptic, binuclear compounds [M2(GaCp*)3(PMe3)2] (M = Pd: 1a, Pt: 1b,
      Cp* = pentamethylcyclopentadienyl) can be obtained if [Pd2(dvds)3] (dvds = 1,3
      divinyl-1,1,3,3-tetramethyldisiloxane) or [Pt(COD)2] (COD = cyclooctadiene) were
      treated with a 3 : 2 ratio of GaCp* and PMe3. A trinuclear complex
      [Pd3(GaCp*)3(PMe3)3] (2) was isolated from in situ prepared [Pd(PMe3)2Me2] and
      treatment with GaCp*. The new complexes were used as starting compounds for
      selective Ga/Zn exchange reactions to afford the dinuclear palladium compound
      [Pd2(ZnCp*)(ZnMe)3(PMe3)5] (3a) and the mononuclear platinum compound
      [Pt(ZnCp*)2(ZnMe)2(PMe3)2] (3b). The effects of a final transition metal count in
      organozinc ligated compounds and stabilization of Lewis acidic fragments like
      [Pd(PPh3)3], [Ni(C2H4)3] or [Mo(CO)5] were presented and discussed. All compounds
      have been fully characterized by (1)H, (13)C, and (31)P NMR spectroscopy, mass
      spectrometry using a liquid injection field desorption ionization (LIFDI) method,
      elemental analysis, and single crystal X-ray diffraction studies and the
      coordination polyhedra were analysed by the method of continuous shape measure
      (CShM).

PMID- 24292373
TI  - Plasmon-enhanced ultraviolet photoluminescence from the hybrid plasmonic Fabry
      Perot microcavity of Ag/ZnO microwires.
AB  - We propose a kind of hybrid plasmonic Fabry-Perot (F-P) microcavity consisting of
      ZnO microwires with quadrate cross-section and planar multilayer metal-insulator
      metal (MIM) homostructures with a nanoscale SiO2 gap in between. MIM
      homostructures can be used to create a micro-resonator that simultaneously
      provides feedback for laser action and supports the coupling between the
      plasmonic waveguide modes and microwire modes across the gap. The hybridization
      of ZnO microwire modes and surface plasmons across the gap forms hybrid plasmonic
      F-P microcavity modes, which are highly confined to the low-loss SiO2 gap region.
      By comparing with bare ZnO microwires, an enhancement in photoluminescence (PL)
      intensity of two orders of magnitude is realized experimentally due to the
      coupling between plasmonic MIM homostructures and ZnO microwires. The
      controllability and miniaturization emission properties of this type of
      microcavity are potentially important for designing laser cavity applications and
      information transmission.

PMID- 24292374
TI  - Co-assembly of a three-dimensional open framework sulfide with a novel linkage
      between an oxygen-encapsulated T3 cluster and a supertetrahedral T2 cluster.
AB  - Solvothermal reactions of S, Ga and Sn using cis-2,6-dimethylmorpholine (DMMP) as
      an organic template, in the presence of a trace amount of H2O at 180  degrees C,
      generated microporous [C6H14NO]14.4[Ga6.40Sn21.60S52O8] material composed of
      hybrid T2 and T3 supertetrahedral clusters with a PtS type topology. 

PMID- 24292375
TI  - Health-related quality of life in children with specific learning disability:
      children's self-reports versus parents' proxy reports.

PMID- 24292376
TI  - Physical properties of K(x)Ni(2-y)Se2 single crystals.
AB  - We have synthesized K0.95(1)Ni1.86(2)Se2 single crystals. The single crystals
      contain K and Ni deficiencies not observed in KNi2Se2 polycrystals. Unlike
      KNi2Se2 polycrystals, the superconductivity is absent in single crystals. The
      detailed physical property study indicates that the K0.95Ni1.86Se2 single
      crystals exhibit heavy-fermion-like characteristics. The transition to a heavy
      fermion state below T ~ 30 K results in an enhancement of the electron-like
      carrier density whereas the magnetic susceptibility shows little anisotropy and
      suggests the presence of both itinerant and localized Ni orbitals.

PMID- 24292377
TI  - Re-interpretation of the evidence for the PVC cell plan supports a Gram-negative
      origin.
AB  - The PVC superphylum consists of the core phyla Planctomycetes, Verrucomicrobia
      and Chlamydiae, together with additional ones. Historically, the cell plan of PVC
      bacteria has been interpreted as an 'exception' to the classical Gram-negative
      (Gneg) one (Fuerst Antonie van Leeuwenhoek 104:451-466, 2013). However recent
      genomic and electron-microscopy data have argued against this exceptional status
      and suggested the need for a reinterpretation of the data in a more classical
      framework. In this perspective, I evaluate the arguments that have recently been
      presented by Fuerst as supporting the PVC cell plan as an 'exception' and present
      an alternative interpretation that is based on proposed evolutionary events that
      may have shaped the PVC genomes and proteomes. This interpretation supports the
      alternative proposal that the PVC cell plan is derived from a Gneg one. 

PMID- 24292378
TI  - Genetic diversity of rhizobia isolated from nodules of the relic species
      Vavilovia formosa (Stev.) Fed.
AB  - Sixteen bacterial strains were isolated from root nodules of Vavilovia formosa
      plants originated from the North Ossetian State Natural Reserve (Caucasus,
      Russia). Phylogenetic analysis of these strains was performed using partial 16S
      rRNA gene and internally transcribed spacer (ITS) sequences. The results showed
      that the isolates belong to three families of root nodule bacteria. Twelve of
      them were related to the genus Rhizobium (family Rhizobiaceae) but four strains
      can be most probably identified as Phyllobacterium-related (family
      Phyllobacteriaceae), Bosea- and Rhodopseudomonas-related (family
      Bradyrhizobiaceae). Amplified fragment length polymorphism clustering was
      congruent with ITS phylogeny but displayed more variability for Rhizobium
      isolates, which formed a single group at the level of 30 % similarity. We expect
      that the isolates obtained can belong to new taxa at genus, species or subspecies
      levels. The results of PCR amplification of the nodulation genes nodC and nodX
      showed their presence in all Rhizobium isolates and one Rhodopseudomonas-related
      isolate. The nodC gene sequences of V. formosa isolates were closely related to
      those of the species Rhizobium leguminosarum bv. viciae but formed separate
      clusters and did not intermingle with any reference strains. The presence of the
      nodX gene, which is necessary for nodulation of Afghan peas (Pisum sativum L.)
      originated from the Middle East, allows the speculation that these wild-type pea
      cultivars may be the closest existing relatives of V. formosa. Thus, the studies
      of genetic diversity and symbiotic genes of V. formosa microsymbionts provide the
      primary information about their phylogeny and contribute to the conservation of
      this relict leguminous species.

PMID- 24292379
TI  - CYP3A4 overexpression enhances apoptosis induced by anticancer agent
      imidazoacridinone C-1311, but does not change the metabolism of C-1311 in CHO
      cells.
AB  - AIM: To examine whether CYP3A4 overexpression influences the metabolism of
      anticancer agent imidazoacridinone C-1311 in CHO cells and the responses of the
      cells to C-1311. METHODS: Wild type CHO cells (CHO-WT), CHO cells overexpressing
      cytochrome P450 reductase (CPR) [CHO-HR] and CHO cells coexpressing CPR and
      CYP3A4 (CHO-HR-3A4) were used. Metabolic transformation of C-1311 and CYP3A4
      activity were measured using RP-HPLC. Flow cytometry analyses were used to
      examine cell cycle, caspase-3 activity and cell apoptosis. The expression of pH
      6.0-dependent beta-galactosidase (SA-beta-gal) was studied to evaluate
      accelerated senescence. ROS generation was analyzed with CM-H2 DCFDA staining.
      RESULTS: CYP3A4 overexpression did not change the metabolism of C-1311 in CHO
      cells: the levels of all metabolites of C-1311 increased with the exposure time
      to a similar extent, and the differences in the peak level of the main metabolite
      M3 were statistically insignificant among the three CHO cell lines. In CHO-HR-3A4
      cells, C-1311 effectively inhibited CYP3A4 activity without affecting CYP3A4
      protein level. In the presence of C-1311, CHO-WT cells underwent rather stable
      G2/M arrest, while the two types of transfected cells only transiently
      accumulated at this phase. C-1311-induced apoptosis and necrosis in the two types
      of transfected cells occurred with a significantly faster speed and to a greater
      extent than in CHO-WT cells. Additionally, C-1311 induced ROS generation in the
      two types of transfected cells, but not in CHO-WT cells. Moreover, CHO-HR-3A4
      cells that did not die underwent accelerated senescence. CONCLUSION: CYP3A4
      overexpression in CHO cells enhances apoptosis induced by C-1311, whereas the
      metabolism of C-1311 is minimal and does not depend on CYP3A4 expression.

PMID- 24292380
TI  - Combination effects of ZSET1446/ST101 with memantine on cognitive function and
      extracellular acetylcholine in the hippocampus.
AB  - In the novel object recognition task, ZSET1446 (also coded as ST101) enhanced
      object recognition memory in mice and ameliorated cognitive impairment caused by
      scopolamine in rats. The enhancement induced by ZSET1446 in mice was abolished by
      injection of mechamylamine, a nonselective antagonist of nicotinic acetylcholine
      (ACh) receptors, or dihydro-beta-erythroidine, a selective antagonist against the
      alpha4 subunit of nicotinic ACh receptors. These results suggest that the
      procognitive effect of ZSET146 is probably mediated by stimulation of nicotinic
      receptors. Memantine was also effective in these tests and concomitant
      administration of subeffective doses of ZSET1446 and memantine significantly
      ameliorated the cognitive performance in the novel object recognition task in
      both mice and rats. Moreover, oral administration of ZSET1446 or memantine
      increased the extracellular level of ACh in the hippocampus as compared with the
      control. Further, concomitant administration of subeffective doses of ZSET1446
      and memantine significantly increased the extracellular level of ACh as compared
      with the group of ZSET1446 or memantine alone. These results suggest that these
      two compounds have a synergistic effect on the cognitive function possibly by
      synergistic increase in the extracellular level of ACh in the hippocampus, and
      that the combination therapy of these compounds might be effective in clinical
      settings. 

PMID- 24292381
TI  - Fibrates reduce triacylglycerol content by upregulating adipose triglyceride
      lipase in the liver of rats.
AB  - Hepatic triacylglycerol (TAG) homeostasis is maintained by carefully regulated
      balance between its synthesis and disposal. Impairment in this balance causes
      steatosis. The aims of this study were i) to uncover whether fibrates control TAG
      concentration through the action of adipose triglyceride lipase (ATGL) and ii) to
      compare the potency of the effects on ATGL expression and TAG concentration among
      fenofibrate, bezafibrate, and clofibric acid in the liver of rats. Treatments of
      rats with the three fibrates induced ATGL and concomitantly decreased hepatic TAG
      concentration. The upregulation of ATGL was likely mediated through the
      activation of peroxisome proliferator-activated receptor alpha. Fibrates also
      expanded capacity of fatty acid beta-oxidation. Importantly, three fibric acids
      (fenofibric, bezafibric, and clofibric acids) that are active metabolites formed
      in the liver exhibited almost the same potency to elevate ATGL expression in
      vivo, despite the fact that there were considerable differences in this regard
      among fenofibrate, bezafibrate, and clofibric acid when compared on the basis of
      their dosage. These results suggest that ATGL represents a potential therapeutic
      target for ameliorating hepatic steatosis and that fibric acids are promising
      agents to ameliorate and/or protect against hepatic steatosis. 

PMID- 24292382
TI  - Significance of the vascular concentration of angiotensin II-receptor blockers on
      the mechanism of lowering blood pressure in spontaneously hypertensive rats.
AB  - To clarify the hypotensive mechanism of angiotensin II receptor-blockers (ARBs),
      drug concentrations in plasma and vascular tissues were measured using matrix
      assisted laser desorption ionization time-of-flight mass spectrometry and imaging
      mass spectrometry. In spontaneously hypertensive rats, systolic blood pressure
      (SBP) was measured 2 and 24 h after administration of candesartan cilexetil (0.3,
      1, or 3 mg/kg) or azilsartan (0.3, 1, or 3 mg/kg). SBP was similarly lowered 2 h
      after administration of azilsartan or candesartan cilexetil, but it was
      significantly lower in the azilsartan-treated group than in the candesartan
      cilexetil-treated group at 24 h. Angiotensin II-induced vascular contractions
      were similarly attenuated 2 h after administration of these drugs, and the
      contractions were significantly lower in the azilsartan-treated group at 24 h.
      Although plasma concentration was significantly lower in the azilsartan-treated
      group at 24 h, vascular concentration of azilsartan was significantly greater
      than that of candesartan. Significant correlations between SBP and vascular
      concentrations were observed both at 2 and 24 h, while no significant correlation
      was observed between plasma and vascular concentrations. In conclusion, the
      mechanism of ARB-induced hypotension is likely to depend on vascular
      concentrations rather than plasma concentrations. 

PMID- 24292383
TI  - Two distinct serotonin receptors co-mediate non-photic signals to the circadian
      clock.
AB  - Several lines of evidence indicate that serotonin type 7 (5-HT7) receptors play a
      critical role for non-photic resetting of the mammalian circadian clock; however,
      the contributions of other types of 5-HT receptors to non-photic entrainment are
      not yet clarified. The present study demonstrates that MKC-242, a selective 5
      HT1A receptor agonist, can evoke a non-photic-like phase-response in hamsters in
      vivo. This phase-shifting response to MKC-242 was antagonized not only by the
      selective 5-HT1A receptor blocker WAY100635 but also by the selective 5-HT7
      receptor blocker DR4004. These suggest that synchronous activation of 5-HT1A and
      5-HT7 receptors mediates non-photic signals to the hamster circadian clock. 

PMID- 24292386
TI  - Supraspinatus rupture at the musculotendinous junction in a young woman.
AB  - The vast majority of rotator cuff tears occur within the tendon or as an avulsion
      from the greater tuberosity. Supraspinatus injury at the musculotendinous
      junction is a very uncommon event. We describe a case of supraspinatus rupture at
      the musculotendinous junction, with successful conservative treatment. It
      occurred in a 23-year-old woman, the youngest patient with this uncommon type of
      injury. To our knowledge, this is the first case of rupture of the supraspinatus
      muscle at the musculotendinous junction in a young woman and the second in a
      woman.

PMID- 24292387
TI  - Spontaneous testicular tubular hypoplasia/atrophy in the Gottingen minipig: a
      retrospective study.
AB  - The aim of this retrospective study was to assess the incidence and severity of
      tubular atrophy/hypoplasia in the testes of 104 control Gottingen minipigs aged
      4.5 to 15 months. The finding was termed "tubular hypoplasia/atrophy" according
      to published descriptions for the dog. It included different microscopic changes
      that were considered part of a continuum, namely seminiferous epithelium
      vacuolation, presence of multinucleated germ cells in the tubular lumen, and
      decreased numbers (hypospermatogenesis) or absence of germ cells. This
      retrospective study demonstrates that tubular hypoplasia/atrophy is present in
      more than 70% of Gottingen minipigs and can occur at a marked severity in control
      animals. It correlated with a higher level of cell debris and a decrease in sperm
      content in the epididymides and with lower absolute and relative testes weights.
      There was no correlation with the weight of other sexual organs, total
      bodyweight, or age, which demonstrates that this change was not related to sexual
      immaturity. The distinction between this background finding and a compound
      related effect could be challenging for the pathologist.

PMID- 24292385
TI  - Effects of alcohol on automated and controlled driving performances.
AB  - RATIONALE: Alcohol is the most frequently detected substance in fatal automobile
      crashes, but its precise mode of action is not always clear. OBJECTIVE: The
      present study was designed to establish the influence of blood alcohol
      concentration as a function of the complexity of the scenarios. Road scenarios
      implying automatic or controlled driving performances were manipulated in order
      to identify which behavioral parameters were deteriorated. METHOD: A single blind
      counterbalanced experiment was conducted on a driving simulator. Sixteen
      experienced drivers (25.3 +/- 2.9 years old, 8 men and 8 women) were tested with
      0, 0.3, 0.5, and 0.8 g/l of alcohol. Driving scenarios varied: road tracking, car
      following, and an urban scenario including events inspired by real accidents.
      Statistical analyses were performed on driving parameters as a function of
      alcohol level. RESULTS: Automated driving parameters such as standard deviation
      of lateral position measured with the road tracking and car following scenarios
      were impaired by alcohol, notably with the highest dose. More controlled
      parameters such as response time to braking and number of crashes when confronted
      with specific events (urban scenario) were less affected by the alcohol level.
      CONCLUSION: Performance decrement was greater with driving scenarios involving
      automated processes than with scenarios involving controlled processes.

PMID- 24292388
TI  - Species-specific inflammatory responses as a primary component for the
      development of glomerular lesions in mice and monkeys following chronic
      administration of a second-generation antisense oligonucleotide.
AB  - Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense
      oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation,
      with secondary tubular degeneration. Glomerulopathy occurred in both species with
      species-specific characteristics. Glomerular lesions in mice were characterized
      by progressive hyaline matrix accumulation, accompanied by the presence of renal
      amyloid and with subsequent papillary necrosis. Early changes involved glomerular
      endothelial hypertrophy and degeneration, but the chronic glomerular amyloid and
      hyaline alterations in mice appeared to be species specific. An immune-mediated
      mechanism for the glomerular lesions in mice was supported by early inflammatory
      changes including increased expression of inflammatory cytokines and other
      immunomodulatory genes within the renal cortex, increased stimulation of CD68
      protein, and systemic elevation of monocyte chemotactic protein 1. In contrast,
      kidneys from monkeys given drisapersen chronically showed less severe glomerular
      changes characterized by increased mesangial and inflammatory cells, endothelial
      cell hypertrophy, and subepithelial and membranous electron-dense deposits, with
      ultrastructural and immunohistochemical characteristics of complement and
      complement-related fragments. Lesions in monkeys resembled typical features of C3
      glomerulopathy, a condition described in man and experimental animals to be
      linked to dysregulation of the alternative complement pathway. Thus,
      inflammatory/immune mechanisms appear critical to glomerular injury with species
      specific sensitivities for mouse and monkey. The lower observed proinflammatory
      activity in humans as compared to mice and monkeys may reflect a lower risk of
      glomerular injury in patients receiving AON therapy. 

PMID- 24292389
TI  - Relationship of body weight parameters with the incidence of common spontaneous
      tumors in Tg.rasH2 mice.
AB  - The mechanistic relationship between increased food consumption, increased body
      weights, and increased incidence of tumors has been well established in 2-year
      rodent models. Body weight parameters such as initial body weights, terminal body
      weights, food consumption, and the body weight gains in grams and percentages
      were analyzed to determine whether such relationship exists between these
      parameters with the incidence of common spontaneous tumors in Tg.rasH2 mice. None
      of these body weight parameters had any statistically significant relationship
      with the incidence of common spontaneous tumors in Tg.rasH2 males, namely lung
      tumors, splenic hemangiosarcomas, nonsplenic hemangiosarcomas, combined incidence
      of all hemangiosarcomas, and Harderian gland tumors. These parameters also did
      not have any statistically significant relationship with the incidence of lung
      and Harderian gland tumors in females. However, in females, increased initial
      body weights did have a statistically significant relationship with the
      nonsplenic hemangiosarcomas, and increased terminal body weights did have a
      statistically significant relationship with the incidence of splenic
      hemangiosarcomas, nonsplenic hemangiosarcomas, and the combined incidence of all
      hemangiosarcomas. In addition, increased body weight gains in grams and
      percentages had a statistically significant relationship with the combined
      incidence of all hemangiosarcomas in females, but not separately with splenic and
      nonsplenic hemangiosarcomas. 

PMID- 24292384
TI  - Using genetic findings in autism for the development of new pharmaceutical
      compounds.
AB  - RATIONALE: The main reason for the current lack of effective treatments for the
      core symptoms of autism is our limited understanding of the biological mechanisms
      underlying this heterogeneous group of disorders. A primary value of genetic
      research is enhancing our insight into the biology of autism through the study of
      identified autism risk genes. OBJECTIVES: In the current review we discuss (1)
      the genes and loci that are associated with autism, (2) how these provide us with
      essential cues as to what neurobiological mechanisms may be involved, and (3) how
      these mechanisms may be used as targets for novel treatments. Next, we provide an
      overview of currently ongoing clinical trials registered at clinicaltrials.gov
      with a variety of compounds. Finally, we review current approaches used to
      translate knowledge derived from gene discovery into novel pharmaceutical
      compounds and discuss their pitfalls and problems. CONCLUSIONS: An increasing
      number of genetic variants associated with autism have been identified. This will
      generate new ideas about the biological mechanisms involved in autism, which in
      turn may provide new leads for the development of novel pharmaceutical compounds.
      To optimize this pipeline of drug discovery, large-scale international
      collaborations are needed for gene discovery, functional validation of risk
      genes, and improvement of clinical outcome measures and clinical trial
      methodology in autism.

PMID- 24292390
TI  - Adaptive parotid gland hypertrophy induced by dietary treatment of GSE in rats.
AB  - In a 13-week feeding toxicity study of grape skin extract (GSE) performed
      previously, 5.0% GSE showed diffuse hypertrophy and basophilia in rat parotid
      glands. To clarify whether the change in the parotid glands was an adverse effect
      of GSE, 6-week-old male F344 rats were fed a diet containing 5.0% GSE or were
      administered a dose corresponding to the dietary concentration via gavage for 4
      weeks, and the treatment was stopped for 2 weeks. To ascertain the effect of
      astringency, other animals were fed a diet containing 5.0% tannic acid (TA) using
      the same protocol as the GSE feed group. Control groups were fed a basal diet or
      were administered sterilized distilled water by gavage. In the GSE and TA feed
      groups, diffuse severe hypertrophy and basophilia in the parotid glandular
      epithelial cells were observed. Macroscopic, microscopic, and ultrastructural
      characteristics consistent with cellular hypertrophy was less apparent after the
      recovery period in both feed groups. In contrast, no changes were observed in the
      parotid glands of the gavage GSE and control groups at week 4. Based on these
      findings of parotid hypertrophy without cytotoxicity, the data from this and
      previous studies suggest that hypertrophy of the parotid glands induced by
      feeding treatment with GSE is an adaptive non-adverse effect that is reversible
      upon removal of the sialotrophic agent.

PMID- 24292391
TI  - The effect of creep on human lumbar intervertebral disk impact mechanics.
AB  - The intervertebral disk (IVD) is a highly hydrated tissue, with interstitial
      fluid making up 80% of the wet weight of the nucleus pulposus (NP), and 70% of
      the annulus fibrosus (AF). It has often been modeled as a biphasic material,
      consisting of both a solid and fluid phase. The inherent porosity and osmotic
      potential of the disk causes an efflux of fluid while under constant load, which
      leads to a continuous displacement phenomenon known as creep. IVD compressive
      stiffness increases and NP pressure decreases as a result of creep displacement.
      Though the effects of creep on disk mechanics have been studied extensively, it
      has been limited to nonimpact loading conditions. The goal of this study is to
      better understand the influence of creep and fluid loss on IVD impact mechanics.
      Twenty-four human lumbar disk samples were divided into six groups according to
      the length of time they underwent creep (tcreep = 0, 3, 6, 9, 12, 15 h) under a
      constant compressive load of 400 N. At the end of tcreep, each disk was subjected
      to a sequence of impact loads of varying durations (timp = 80, 160, 320, 400,
      600, 800, 1000 ms). Energy dissipation (DeltaE), stiffness in the toe (ktoe) and
      linear (klin) regions, and neutral zone (NZ) were measured. Analyzing
      correlations with tcreep, there was a positive correlation with DeltaE and NZ,
      along with a negative correlation with ktoe. There was no strong correlation
      between tcreep and klin. The data suggest that the IVD mechanical response to
      impact loading conditions is altered by fluid content and may result in a disk
      that exhibits less clinical stability and transfers more load to the AF. This
      could have implications for risk of diskogenic pain as a function of time of day
      or tissue hydration. 

PMID- 24292393
TI  - Determination of 226Ra contamination depth in soil using the multiple photopeaks
      method.
AB  - Radioactive contamination presents a diverse range of challenges in many
      industries. Determination of radioactive contamination depth plays a vital role
      in the assessment of contaminated sites, because it can be used to estimate the
      activity content. It is determined traditionally by measuring the activity
      distributions along the depth. This approach gives accurate results, but it is
      time consuming, lengthy and costly. The multiple photopeaks method was developed
      in this work for (226)Ra contamination depth determination in a NORM contaminated
      soil using in-situ gamma spectrometry. The developed method bases on linear
      correlation between the attenuation ratio of different gamma lines emitted by
      (214)Bi and the (226)Ra contamination depth. Although this method is approximate,
      but it is much simpler, faster and cheaper than the traditional one. This method
      can be applied for any case of multiple gamma emitter contaminant. 

PMID- 24292392
TI  - Self-renewal as a therapeutic target in human colorectal cancer.
AB  - Tumor recurrence following treatment remains a major clinical challenge. Evidence
      from xenograft models and human trials indicates selective enrichment of cancer
      initiating cells (CICs) in tumors that survive therapy. Together with recent
      reports showing that CIC gene signatures influence patient survival, these
      studies predict that targeting self-renewal, the key 'stemness' property unique
      to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that
      tumor formation and, more specifically, human colorectal CIC function are
      dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1
      inhibits the ability of colorectal CICs to self-renew, resulting in the
      abrogation of their tumorigenic potential. Treatment of primary colorectal cancer
      xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss
      with long-term and irreversible impairment of tumor growth. Targeting the BMI-1
      related self-renewal machinery provides the basis for a new therapeutic approach
      in the treatment of colorectal cancer. 

PMID- 24292395
TI  - The effect of high level natural ionizing radiation on expression of PSA, CA19-9
      and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.
AB  - Since several high level natural radiation areas (HLNRAs) exist on our planet,
      considerable attention has been drawn to health issues that may develop as the
      result of visiting or living in such places. City of Ramsar in Iran is an HNLRA,
      and is a tourist attraction mainly due to its hot spas. However, the growing
      awareness over its natural radiation sources has prompted widespread scientific
      investigation at national level. In this study, using an ELISA method, the level
      of expression of three tumor markers known as carcinoembryonic antigen (CEA),
      prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum
      of 40 local men of Ramsar (subject group) was investigated and compared to 40 men
      from the city of Noshahr (control group). Noshahr was previously identified as a
      normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar.
      According to statistical analysis, there was a significant difference in the
      levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of
      Ramsar being considerably higher. CEA level did not show any difference. Although
      some of the volunteers tested positive to the markers, they were in good health
      as confirmed by the physician. Moreover, the high number of positive markers in
      Noshahr was considerable. Therefore, future study is needed to further validate
      this result and to determine the level of positivity to tumor markers in both
      cities. 

PMID- 24292396
TI  - Deforestation and forest management in southern Ethiopia: investigations in the
      Chencha and Arbaminch areas.
AB  - Long-term human impacts are considered to be the prime cause of unsustainable
      forest exploitation in Ethiopia. Yet there exist well-established systems and a
      wealth of local experience in maintaining and managing forests. This study
      explores the trends and driving forces of deforestation plus traditional
      practices regarding sustainable forest use and management in the Chencha and
      Arbaminch areas, Southern Ethiopia. Satellite image analysis (images from 1972,
      1984 and 2006) combined with field surveys were used to detect and map changes in
      forest cover. Household interviews and group discussions with experienced and
      knowledgeable persons were also employed. The results show a 23 % decline in
      forest cover between 1972 and 2006 with the most significant change from 1986 to
      2006. Change was greatest in the lowlands and remarkable episodic forest changes
      also occurred, suggesting nonlinear spatial and temporal forest cover dynamics.
      According to farmers, the main driver of deforestation is agricultural land
      expansion in response to local population increases and a decline in agricultural
      production. Growing local and regional fuel wood demand is another chief cause.
      Despite these issues, remarkable relicts of natural forests remain and trees on
      farmland, around homesteads and on fields in every village are basic elements of
      farm activities and social systems. This demonstrates the effect of cumulative
      traditional knowledge and long-term local experience with forest management and
      preservation. Therefore, these practices should be promoted and advanced through
      the integration of local knowledge and forest management practices in the design
      and implementation of sustainable environmental planning and management.

PMID- 24292394
TI  - Concentrations and fluxes of dissolved uranium in the Yellow River estuary:
      seasonal variation and anthropogenic (Water-Sediment Regulation Scheme) impact.
AB  - The Water-Sediment Regulation Scheme (WSRS) of the Yellow River is a procedure
      implemented annually from June to July to expel sediments deposited in Xiaolangdi
      and other large middle-reach reservoirs and to scour the lower reaches of the
      river, by controlling water and sediment discharges. Dissolved uranium isotopes
      were measured in river waters collected monthly as well as daily during the 2010
      WSRS (June 19-July 16) from Station Lijin (a hydrologic station nearest to the
      Yellow River estuary). The monthly samples showed dissolved uranium
      concentrations of 3.85-7.57 MUg l(-1) and (234)U/(238)U activity ratios of 1.24
      1.53. The concentrations were much higher than those reported for other global
      major rivers, and showed seasonal variability. Laboratory simulation experiments
      showed significant uranium release from bottom and suspended sediment. The
      uranium concentrations and activity ratios differed during the two stages of the
      WSRS, which may reflect desorption/dissolution of uranium from suspended river
      sediments of different origins. An annual flux of dissolved uranium of 1.04 *
      10(8) g y(-1) was estimated based on the monthly average water discharge and
      dissolved uranium concentration in the lower reaches of the Yellow River. The
      amount of dissolved uranium (2.65 * 10(7) g) transported from the Yellow River to
      the sea during the WSRS constituted about 1/4 of the annual flux. 

PMID- 24292397
TI  - Large intercostal pulmonary hernia secondary to limited-access aortic valve
      surgery: video-assisted thoracoscopic technique repair.

PMID- 24292398
TI  - Comparison of severe healthcare-associated pneumonia with severe community
      acquired pneumonia.
AB  - BACKGROUND: We compared the demographic characteristics and outcomes of patients
      with severe healthcare-associated pneumonia (HCAP) to those with severe community
      acquired pneumonia (CAP). METHODS: This was a retrospective study of
      prospectively collected data from all consecutive patients with severe pneumonia
      who were admitted to the hospital through the emergency department between
      January 2008 and December 2010. RESULTS: During the study period, 247 patients
      had severe pneumonia; of these, 107 had severe CAP and 140 had severe HCAP. There
      was no significant difference in demographic characteristics between the two
      groups, except for comorbidities. Although the incidence of potentially drug
      resistant pathogens was higher in patients with severe HCAP than in those with
      severe CAP (34 vs. 6 %, P = 0.004), there was no statistically significant
      difference in the rate of inappropriate antibiotic treatment (16 vs. 3 %, P =
      0.143). Finally, clinical outcomes, such as intensive care unit admission, length
      of hospital stay, and in-hospital mortality, were not different between the two
      groups. In a multiple logistic regression analysis, a higher PSI score (adjusted
      OR 1.01; 95 % CI 1.00-1.02; P = 0.024) and the need for mechanical ventilation
      (adjusted OR 2.62; 95 % CI 1.37-5.00; P = 0.004) were independently associated
      with in-hospital mortality. However, the type of pneumonia was not associated
      with in-hospital mortality after adjusting for potential confounding factors.
      CONCLUSIONS: The severity of illness rather than the type of pneumonia might be
      associated with in-hospital mortality in patients with severe pneumonia.

PMID- 24292399
TI  - Induction of female-to-male sex change in adult zebrafish by aromatase inhibitor
      treatment.
AB  - This study investigated whether undifferentiated germ and/or somatic stem cells
      remain in the differentiated ovary of a species that does not undergo sex changes
      under natural conditions and retain their sexual plasticity. The effect of
      aromatase inhibitor (AI)-treatment on sexually mature female zebrafish was
      examined. A 5-month AI treatment caused retraction of the ovaries after which
      testes-like organs appeared, and cyst structures filled with spermatozoa-like
      cells were observed in sections of these tissues. Electron microscopic
      observations revealed that these cells appeared as large sperm heads without
      tails. Sperm formation was re-examined after changing the diet to an AI-free
      food. A large number of normal sperm were obtained after eight weeks, and no
      formation of ovarian tissue was observed. Artificial fertilization using sperm
      from the sex-changed females was successful. These results demonstrated that sex
      plasticity remains in the mature ovaries of this species. 

PMID- 24292401
TI  - Optimal tolerability and high efficacy of a modified schedule of lapatinib
      capecitabine in advanced breast cancer patients.
AB  - PURPOSE: Diarrhea in relation to the lapatinib-capecitabine regimen is a common
      and debilitating side effect which may interfere with optimal treatment delivery.
      We performed a post hoc analysis in human epidermal growth factor receptor 2
      positive advanced breast cancer patients treated with a modified schedule in its
      administration, aimed primarily to evaluate grade (G) >= 2 diarrhea incidence
      and, secondarily, treatment efficacy. PATIENTS AND METHODS: Treatment schedule
      consisted of lapatinib 1,250 mg daily for the first 10 days, then in combination
      with capecitabine, 2,000 mg/m(2), starting day 11 for the first cycle, and
      thereafter from day 8, for 14 days of a 21-day cycle, in 3 daily administrations.
      Lapatinib was dissolved in water, and cholestyramine was continuously given twice
      a day. RESULTS: Among 38 patients treated and analyzed, the incidence of G >= 2
      diarrhea was 13.2 %. In 28 patients diarrhea was not observed, while G1-2
      diarrhea was reported in 9 (23.7 %) patients; a single episode of G3 diarrhea was
      observed in 1 (2.6 %) patient. Overall response rate was 34.2 %, clinical benefit
      55.3 %, and median progression-free survival 10 months. CONCLUSION: The results
      of the present post hoc analysis are very encouraging, both in terms of
      tolerability and treatment efficacy, and all data compare favorably with previous
      reports of "conventional" administration of the lapatinib-capecitabine regimen.

PMID- 24292400
TI  - Predictive factors for the development of brain metastases in patients with
      malignant melanoma: a study by the Anatolian society of medical oncology.
AB  - BACKGROUND: The development of brain metastases (BMs) was associated with poor
      prognosis in melanoma patients. Patients with BMs have a median survival of <6
      months. Melanoma is the third most common tumor to metastasize to the brain with
      a reported incidence of 10-40 %. Our aim was to identify factors predicting
      development of BMs and survival. PATIENTS AND METHODS: We performed a
      retrospective analysis of 470 melanoma patients between 2000 and 2012. The
      logistic regression analyses were used to identify the clinicopathological
      features of primary melanoma that are predictive of BMs development and survival
      after a diagnosis of brain metastases. RESULTS: There were 52 patients (11.1 %)
      who developed melanoma BMs during the study period. The analysis of post-BMs with
      Kaplan-Meier curves has resulted in a median survival rate of 4.1 months (range
      2.9-5.1 months). On logistic regression analysis site of the primary tumor on the
      head and neck (p = 0.002), primary tumor thickness (Breslow >4 mm) (p = 0.008),
      ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were
      found to be significantly associated with the development of BMs. In univariate
      analysis, tumor thickness and performance status had a significant influence on
      post-BMs survival. In multivariate analysis, these clinicopathologic factors were
      not remained as significant predictive factors. CONCLUSIONS: Our results revealed
      the importance of primary tumor characteristics associated with the development
      of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic >=N2
      disease were found to be significant predictors of BMs development.

PMID- 24292402
TI  - Impact of BMI on serum estradiol and bone turnover markers in postmenopausal
      women with hormone-sensitive early breast cancer treated with anastrozole.
AB  - PURPOSE: Obesity increases the risk of all-cause and breast cancer mortality. As
      obese patients have higher levels of aromatase enzyme activity, conflicting
      results on the effect of body mass index (BMI) of a standard dose aromatase
      inhibitor on estradiol depletion have been reported. METHODS: We prospectively
      investigated the effect of BMI on the efficacy of anastrozole in 70
      postmenopausal women with early, ER-positive breast cancer to decrease serum
      estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml
      over 24 months. Additionally, we examined the changes of bone markers expecting
      an inverse relationship. RESULTS: Overall, estradiol decreased from 12.6 pg/ml
      (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast,
      carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of
      type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD =
      0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both).
      Baseline estradiol comprised significant differences comparing normal weight with
      overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months,
      overweight and obese patients showed a slightly, but insignificantly higher
      concentrations of estradiol compared to normal weight subjects. We found
      differences of CTX in comparison between normal weight and obese patients (0.33
      vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a
      significant BMI-independent increase in CTX. CONCLUSIONS: Estradiol
      concentrations in postmenopausal women with early, ER-positive breast cancer on
      anastrozole were significantly different in normal weight versus overweight or
      obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a
      notable increase in the first 12 months of anastrozole treatment, stabilizing
      thereafter.

PMID- 24292403
TI  - [Von Hippel-Lindau syndrome].
AB  - Von Hippel-Lindau syndrome is an autosomal dominant inherited phacomatosis with a
      predisposition for the central nervous system and retina. There is variable
      expression with hemangioblastomas in the brain, medulla oblongata, spinal chord,
      renal carcinoma, pheochromocytoma, pancreatic cysts and islet cell tumors as well
      as tumors of the endolymphatic sac of the inner ear. Clinical symptoms occur
      first after an age of approximately 30 years. Magnetic resonance imaging (MRI) of
      the neuroaxis is indicated in all patients with a suspicion of von Hippel-Lindau
      syndrome. 

PMID- 24292404
TI  - Osteoblasts stimulate the osteogenic and metastatic progression of castration
      resistant prostate cancer in a novel model for in vitro and in vivo studies.
AB  - Castration-resistant prostate cancer (CRPC) is strongly associated with sclerotic
      bone metastases and poor prognosis. Models that mimic human CRPC are needed to
      identify the mechanisms for prostate cancer (PC) growth in bone and to develop
      new therapeutic strategies. We characterize a new model, LNCaP-19, and
      investigate the interaction between tumor cells and osteoblasts in the sclerotic
      tumor response of CRPC. Osteogenic profiling of PC cell lines (LNCaP-19, LNCaP,
      C4-2B4, and PC-3) was performed by gene expression arrays and mineral staining.
      Conditioned medium from MC3T3-E1 was used for osteoblast stimulation of CRPC
      cells. The capacity of LNCaP-19 cells to induce sclerotic lesions was assessed in
      intratibial xenografts and verified by serum markers, histological analysis and
      bone mineral density (BMD) measurements. The CRPC cell line LNCaP-19 expresses a
      pronounced osteogenic profile compared to its parental androgen-dependent cell
      line LNCaP. Osteoblast-derived factors further increase the expression of genes
      known to enhance metastatic progression of PC. LNCaP-19 forms sclerotic tumors in
      tibia of castrated mice as evident by increased total BMD (P < 0.01). There was a
      strong correlation between serum osteocalcin and BMD (total: R (2) 0.811, P <
      0.01, trabecular: R (2) 0.673, P < 0.05). For the first time we demonstrate that
      a CRPC cell line generated in vitro has osteogenic capacity and that osteomimicry
      can be an inherent feature of these cells. Osteoblast-derived factors further
      promote the osteogenic and metastatic phenotype in CRPC cells. Altogether, our
      model demonstrates that both tumor cells and osteoblasts are mediators of the
      bone forming process of CRPC.

PMID- 24292406
TI  - Interplay of nanoscale domain purity and size on charge transport and
      recombination dynamics in polymer solar cells.
AB  - Charge transport and bimolecular recombination dynamics were correlated with
      nanomorphology in polymer solar cells. The morphology of
      poly(diketopyrrolopyrrole-terthiophene) (PDPP3T) and phenyl-C61-butyric acid
      methyl ester (PC60BM) blend films was modified using different solvent additives
      namely 1-chloronaphthalene (CN), 1,8-diiodooctane (DIO) and 1,8-octanedithiol
      (ODT) and their role on steady state and transient optoelectronic properties was
      investigated. The energy filtered transmission electron microscopy (EFTEM) images
      showed that additives (e.g. CN and DIO) improved the domain purity which leads to
      significantly higher short circuit current densities (Jsc). However when the
      cells were processed with the ODT additive, the fill factor (FF) and open circuit
      voltage (Voc) decreased dramatically. Films processed with the ODT additive
      showed a smaller domain size but were more connected compared to films processed
      using CN and DIO additives. Transient photocurrent analysis indicates faster
      charge collection in the case of CN and DIO processed solar cells and the slowest
      charge collection in ODT processed solar cells. Interestingly devices processed
      with the ODT additive also showed the longest charge carrier recombination
      lifetime and lowest bimolecular recombination coefficient. This is attributed to
      the smaller donor domains that are connected with each other to provide a more
      interconnected and efficient charge transport matrix but longer pathways in ODT
      films. Such a matrix helped the charge to escape from the donor-acceptor
      interfaces and thus reduces the bimolecular recombination, while the longer
      pathway increases the charge collection time. Further insight is provided into
      the selection of processing conditions to achieve an ideal active layer
      morphology consisting of domains with higher polymer purity and optimal size that
      lead to higher Jsc and FF. 

PMID- 24292405
TI  - Modulation of matrix metalloproteinase-9 secretion from tumor-associated
      macrophage-like cells by proteolytically processed laminin-332 (laminin-5).
AB  - Macrophages infiltrating tumor tissues (tumor-associated macrophages, TAM) affect
      the malignant behaviors of tumor cells. We previously reported that monocytes
      were differentiated into TAM-like cells secreting matrix metalloproteinase (MMP)
      9 by co-culture with tumor cells, and that cell adhesion to extracellular matrix
      (ECM) proteins played a critical role in the differentiation. In this study, we
      found that the monocyte differentiation was promoted by laminin-332 (laminin-5),
      a major epithelial ECM component. We also demonstrated that the proteolytic
      processing of the gamma2 chain of laminin-332 was essential for its activity but
      that the N-terminal short arm of the gamma2 chain inhibited MMP-9 secretion.
      These results indicate that the activity of laminin-332 for monocyte
      differentiation is dynamically regulated by the proteolytic processing of the
      gamma2 chain.

PMID- 24292407
TI  - Incidental GIST after appendectomy in a pediatric patient: a first instance and
      review of pediatric patients with CD117 confirmed GISTs.
AB  - A 7-year-old boy underwent uncomplicated laparoscopic appendectomy for acute
      appendicitis. Incidentally, he was found to have a spindle cell tumor with CD117
      immunopositivity, consistent with gastrointestinal stromal tumor (GIST) in the
      appendix. Although commonly reported in adults, pediatric GISTs are rare
      gastrointestinal malignancies that occur in only 1.4-2.7% of children and
      adolescents. Due to the paucity of reports, data are insufficient to adequately
      characterize tumor behavior, recurrence, and survival. We present the first case
      of pediatric GIST in the appendix. In addition, a review of the literature for
      CD117 confirmed pediatric GISTs was conducted to summarize its clinical features
      and current treatment options.

PMID- 24292408
TI  - Technical innovation in minimally invasive repair of pectus excavatum.
AB  - The aim of study was to introduce technical innovation of MIRPE which reduces the
      risk of cardiac injury. Modification of MIRPE method with semiflexible
      thoracoscope and sternum elevating technique has been used. Volkmann bone hook
      has been inserted percutaneously to the sternum. The hook elevates the sternum
      forward and enlarges the retrosternal space for safer passage of
      thoracoscopically guided introducer. Using semiflexible thoracoscope allows
      better view from various angles via one site of insertion. During the period 2005
      2012, the MIRPE was performed on 29 girls and 151 boys; the mean age at the time
      of surgery was 15.9 years (range 13-18.7 years). The mean Haller index was 4.7
      (range 2.7-20.5). The most common complication was pneumothorax (3.3 %) and the
      incidence of bar displacement was 2 %. The most serious complication was cardiac
      perforation when inserting Lorenz introducer. This occurred in a 16-year-old
      girl; she required urgent sternotomy with right atrial repair and recovered well.
      External elevation of sternum with the hook was used since this case. Subsequent
      113 patients underwent surgery without any serious complications. Technical
      innovation using semiflexible thoracoscope and hook elevation of the sternum
      reduces the risk of cardiac injury. The hook opens the anterior mediastinum space
      effectively and makes the following dissection relatively safe and
      straightforward.

PMID- 24292410
TI  - Dual door entry to exciplex emission in a chimeric DNA duplex containing non
      nucleoside-nucleoside pair.
AB  - Dual door entry to exciplex formation was established in a chimeric DNA duplex
      wherein a fluorescent non-nucleosidic base surrogate () is paired against a
      fluorescent nucleosidic base surrogate (). Packing of the nucleobases via
      intercalative stacking interactions led to an exciplex emission either via FRET
      from the donor or direct excitation of the FRET acceptor . 

PMID- 24292409
TI  - Reconstructing single hepatic artery with two arterial stumps: biliary
      complications in pediatric living donor liver transplantation.
AB  - INTRODUCTION: Liver grafts can at times have two hepatic arterial stumps. This
      can result in a dilemma whether to reconstruct single or both the arteries.
      Hepatic artery (HA) thrombosis is the most dreaded complication in pediatric
      living donor liver transplantation (LDLT) as it can result in biliary
      complications and subsequent graft loss. We herein report the feasibility of
      reconstructing single hepatic artery in pediatric living donor liver
      transplantation having two arterial stumps in the liver graft. MATERIALS AND
      METHODS: From 2008 to 2010, 87 pediatric patients undergoing LDLT were divided
      into three groups. Group 1 (n = 20): two HA stumps with two HA reconstruction,
      Group 2 (n = 22): two HA stumps with one HA reconstruction and Group 3 (n = 45):
      one HA stump with one HA reconstruction. The decision regarding the
      reconstruction of single or multiple HAs was made depending on the pre-operative
      radiological and intraoperative assessments. RESULTS: The incidence of HA
      thrombosis (p = 0.126) and biliary complications (p = 0.617), was similar in the
      three groups. CONCLUSION: Single HA reconstruction does not increase the risk of
      biliary strictures in pediatric LDLT recipients having dual hepatic arterial
      stumps in the liver graft.

PMID- 24292411
TI  - Disorder-driven non-Fermi liquid behavior in single-crystalline Ce2Co0.8Si3.2.
AB  - A single crystal of the Ce-based ternary silicide Ce2Co0.8Si3.2, which
      crystallizes with a hexagonal AlB2-type related structure, was studied by means
      of magnetization, resistivity and heat capacity measurements. The compound was
      characterized as a Kondo paramagnet down to 0.4 K. Its low-temperature behavior
      is dominated by distinct non-Fermi liquid features, most likely arising due to
      structural disorder in the nonmagnetic-atom sublattice.

PMID- 24292412
TI  - Evaluation of a psychoeducation programme for parents of children and adolescents
      with ADHD: immediate and long-term effects using a blind randomized controlled
      trial.
AB  - Recent guidelines for the diagnosis and treatment of attention deficit
      hyperactivity disorder (ADHD) have claimed the possible benefits of
      psychoeducational techniques in the comprehensive management of ADHD. To evaluate
      the efficacy of a psychoeducation programme for parents of children and
      adolescents with ADHD in a clinical setting using a blind randomized trial. 81
      children/adolescents with ADHD were randomly assigned for their families to
      receive either a well-structured psychoeducation programme (intervention group, n
      = 44), or a parent counselling and support intervention (control group, n = 37).
      Measures of child ADHD symptoms, psychopathology, quality of life and family
      stress were taken before and after intervention and after a year follow-up.
      Parents and evaluators were unaware of the condition received. Compared to the
      support control group, the psychoeducation group showed ADHD Index and
      cognitive/inattention levels significantly reduced after the intervention ended
      (Mann-Whitney U = 3.34; p = 0.001; Mann-Whitney U = 3.47; p = 0.001). An
      improvement in the pro-social domain was also observed after 1 year follow-up
      (Mann-Whitney U = -2.37; p = 0.018), and clinical global impression found a
      statistically significant effect for severity over the time. Differences were
      initially found for the impact of the disorder in the family in different
      domains, including emotional and social functioning; these differences were no
      longer significant after alpha correction. No significant differences in quality
      of life or family stress were found in comparison with the control group. This
      psychoeducation programme is a valuable treatment for parents/carers of
      children/adolescents with ADHD, which needs to be considered when evaluating
      different non-pharmacological treatment options. Psychoeducation and other kind
      of non-pharmacological approaches need to be regarded not as a substitute, but as
      a complementary treatment to medications; these approaches might help other very
      crucial aspects of ADHD including social and familiar outcomes.

PMID- 24292413
TI  - Novel long-acting prostacyclin agonist (ONO-1301) with an angiogenic effect:
      promoting synthesis of hepatocyte growth factor and increasing cyclic AMP
      concentration via IP-receptor signaling.
AB  - The purpose of this study was to evaluate the angiogenic potency of ONO-1301, a
      novel prostacyclin agonist, using a murine sponge model. Solutions of ONO-1301 or
      hepatocyte growth factor (HGF), as a positive control, were injected into sponges
      in the backs of mice, daily for 14 days. Hemoglobin and HGF levels in the sponge
      were increased for up to 14 days on daily treatment with ONO-1301 while on HGF
      treatment, they peaked on day 7 and had decreased again by day 14. ONO-1301 also
      upregulated c-Met expression for 14 days in a dose-dependent manner. When the
      mice were pretreated with an antibody to HGF or the prostaglandin I (IP)-receptor
      antagonist CAY10441, the angiogenic effect of ONO-1301 was dramatically reduced.
      Plasma concentrations of cyclic adenosine monophosphate (cAMP) were increased in
      a dose-dependent manner by once daily treatment with ONO-1301 for 14 days. This
      effect was reduced by pretreatment with the IP-receptor antagonist. In
      conclusion, hemoglobin level was increased by repeated treatment with ONO-1301
      for 14 days. It is suggested that ONO-1301 induced angiogenesis by promoting the
      synthesis of HGF and upregulated c-Met expression, followed by an increase in
      cAMP concentrations mediated by IP-receptor signaling. 

PMID- 24292414
TI  - pH-sensitive unimolecular fluorescent polymeric micelles: from volume phase
      transition to optical response.
AB  - Unimolecular fluorescent micelles of star polyelectrolytes with a perylenediimide
      core are very sensitive to changes in pH values. The pH-responsive behavior
      relies on the ionization or deionization of the star polyelectrolytes, which
      causes a reversible volume phase transition and optical response. 

PMID- 24292415
TI  - Cerebral blood flow in a healthy Circle of Willis and two intracranial aneurysms:
      computational fluid dynamics versus four-dimensional phase-contrast magnetic
      resonance imaging.
AB  - Computational fluid dynamics (CFD) opens up multiple opportunities to investigate
      the hemodynamics of the human vascular system. However, due to numerous
      assumptions the acceptance of CFD among physicians is still limited in practice
      and validation through comparison is mandatory. Time-dependent quantitative phase
      contrast magnetic resonance imaging PC-MRI measurements in a healthy volunteer
      and two intracranial aneurysms were carried out at 3 and 7 Tesla. Based on the
      acquired images, three-dimensional (3D) models of the aneurysms were
      reconstructed and used for the numerical simulations. Flow information from the
      MR measurements were applied as boundary conditions. The four-dimensional (4D)
      velocity fields obtained by CFD and MRI were qualitatively as well as
      quantitatively compared including cut planes and vector analyses. For all cases a
      high similarity of the velocity patterns was observed. Additionally, the
      quantitative analysis revealed a good agreement between CFD and MRI. Deviations
      were caused by minor differences between the reconstructed vessel models and the
      actual lumen. The comparisons between diastole and systole indicate that relative
      differences between MRI and CFD are intensified with increasing velocity. The
      findings of this study lead to the conclusion that CFD and MRI agree well in
      predicting intracranial velocities when realistic geometries and boundary
      conditions are provided. Due to the considerably higher temporal and spatial
      resolution of CFD compared to MRI, complex flow patterns can be further
      investigated in order to evaluate their role with respect to aneurysm formation
      or rupture. Nevertheless, special care is required regarding the vessel
      reconstruction since the geometry has a major impact on the subsequent numerical
      results.

PMID- 24292416
TI  - Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord
      blood transplantation without ATG for acute leukemia in complete remission.
AB  - To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand
      incompatibility on outcomes of acute myeloid leukemia (AML) and acute
      lymphoblastic leukemia (ALL) patients in complete remission after single cord
      blood transplantation (CBT), we assessed the outcomes of CBT registered in the
      Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of
      643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized
      according to their KIR ligand incompatibility by determining whether or not they
      expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient-donor pairs
      were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139
      patient-donor pairs were incompatible in the host-versus-graft (HVG) direction.
      Univariate and multivariate analyses showed no significant differences between
      the KIR ligand-incompatible and compatible groups in the GVH direction for both
      AML and ALL patients of overall survival, disease-free survival, relapse
      incidence, non-relapse mortality and acute GVH disease. However, KIR
      incompatibility in the HVG direction ameliorated engraftment in ALL patients
      (hazard ratio 0.66, 95% confidence interval 0.47-0.91, P=0.013). Therefore, there
      were no effects of KIR ligand incompatibility in the GVH direction on single CBT
      outcomes for acute leukemia patients without anti-thymocyte globulin use.
      However, it is necessary to pay attention to KIR incompatibility in the HVG
      direction for engraftment. 

PMID- 24292417
TI  - (18)F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple
      myeloma affords objective evaluation of plasma cell tumor progression and
      therapeutic response to the proteasome inhibitor ixazomib.
AB  - (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed
      tomography (CT) are useful imaging modalities for evaluating tumor progression
      and treatment responses in genetically engineered mouse models of solid human
      cancers, but the potential of integrated FDG-PET/CT for assessing tumor
      development and new interventions in transgenic mouse models of human blood
      cancers such as multiple myeloma (MM) has not been demonstrated. Here we use
      BALB/c mice that contain the newly developed iMyc(DeltaEMU) gene insertion and
      the widely expressed H2-L(d)-IL6 transgene to demonstrate that FDG-PET/CT affords
      an excellent research tool for assessing interleukin-6- and MYC-driven plasma
      cell tumor (PCT) development in a serial, reproducible and stage- and lesion
      specific manner. We also show that FDG-PET/CT permits determination of objective
      drug responses in PCT-bearing mice treated with the investigational proteasome
      inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate
      (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival
      of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One
      outlier mouse presented with primary refractory disease. Our findings demonstrate
      the utility of FDG-PET/CT for preclinical MM research and suggest that this
      method will play an important role in the design and testing of new approaches to
      treat myeloma. 

PMID- 24292418
TI  - A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia
      with STAT-addictive oncokinases.
AB  - Signal transduction and activator of transcription (STAT) proteins are
      extracellular ligand-responsive transcription factors that mediate cell
      proliferation, apoptosis, differentiation, development and the immune response.
      Aberrant signals of STAT induce uncontrolled cell proliferation and apoptosis
      resistance and are strongly involved in cancer. STAT has been identified as a
      promising target for antitumor drugs, but to date most trials have not been
      successful. Here, we demonstrated that a novel STAT inhibitor, OPB-31121,
      strongly inhibited STAT3 and STAT5 phosphorylation without upstream kinase
      inhibition, and induced significant growth inhibition in various hematopoietic
      malignant cells. Investigation of various cell lines suggested that OPB-31121 is
      particularly effective against multiple myeloma, Burkitt lymphoma and leukemia
      harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities
      dependent on STAT3/5. Using an immunodeficient mouse transplantation system, we
      showed the significant antitumor effect of OPB-31121 against primary human
      leukemia cells harboring these aberrant kinases and its safety for normal human
      cord blood cells. Finally, we demonstrated a model to overcome drug resistance to
      upstream kinase inhibitors with a STAT inhibitor. These results suggested that
      OPB-31121 is a promising antitumor drug. Phase I trials have been performed in
      Korea and Hong Kong, and a phase I/II trial is underway in Japan. 

PMID- 24292419
TI  - Adaptive semiconductor/electrocatalyst junctions in water-splitting photoanodes.
AB  - High-efficiency photoelectrochemical water-splitting devices require the
      integration of electrocatalysts (ECs) with light-absorbing semiconductors (SCs),
      but the energetics and charge-transfer processes at SC/EC interfaces are poorly
      understood. We fabricate model EC-coated single-crystal TiO2 electrodes and
      directly probe SC/EC interfaces in situ using two working electrodes to
      independently monitor and control the potential and current at both the SC and
      the EC. We discover that redox-active ion-permeable ECs such as Ni(OH)2 or NiOOH
      yield 'adaptive' SC/EC junctions where the effective Schottky barrier height
      changes in situ with the oxidation level of the EC. In contrast, dense, ion
      impermeable IrOx ECs yield constant-barrier-height 'buried' junctions. Conversion
      of dense, thermally deposited NiOx on TiO2 into ion-permeable Ni(OH)2 or NiOOH
      correlated with increased apparent photovoltage and fill factor. These results
      provide new insight into the dynamic behaviour of SC/EC interfaces to guide the
      design of efficient SC/EC devices. They also illustrate a new class of adaptive
      semiconductor junctions.

PMID- 24292421
TI  - Direct visualization of magnetoelectric domains.
AB  - The coupling between the magnetic and electric dipoles in multiferroic and
      magnetoelectric materials holds promise for conceptually novel electronic
      devices. This calls for the development of local probes of the magnetoelectric
      response, which is strongly affected by defects in magnetic and ferroelectric
      ground states. For example, multiferroic hexagonal rare earth manganites exhibit
      a dense network of boundaries between six degenerate states of their crystal
      lattice, which are locked to both ferroelectric and magnetic domain walls. Here
      we present the application of a magnetoelectric force microscopy technique that
      combines magnetic force microscopy with in situ modulating high electric fields.
      This method allows us to image the magnetoelectric response of the domain
      patterns in hexagonal manganites directly. We find that this response changes
      sign at each structural domain wall, a result that is corroborated by symmetry
      analysis and phenomenological modelling, and provides compelling evidence for a
      lattice-mediated magnetoelectric coupling. The direct visualization of
      magnetoelectric domains at mesoscopic scales opens up explorations of emergent
      phenomena in multifunctional materials with multiple coupled orders. 

PMID- 24292420
TI  - Epithelial bridges maintain tissue integrity during collective cell migration.
AB  - The ability of skin to act as a barrier is primarily determined by the efficiency
      of skin cells to maintain and restore its continuity and integrity. In fact,
      during wound healing keratinocytes migrate collectively to maintain their
      cohesion despite heterogeneities in the extracellular matrix. Here, we show that
      monolayers of human keratinocytes migrating along functionalized micropatterned
      surfaces comprising alternating strips of extracellular matrix (fibronectin) and
      non-adherent polymer form suspended multicellular bridges over the non-adherent
      areas. The bridges are held together by intercellular adhesion and are subjected
      to considerable tension, as indicated by the presence of prominent actin bundles.
      We also show that a model based on force propagation through an elastic material
      reproduces the main features of bridge maintenance and tension distribution. Our
      findings suggest that multicellular bridges maintain tissue integrity during
      wound healing when cell-substrate interactions are weak and may prove helpful in
      the design of artificial scaffolds for skin regeneration.

PMID- 24292422
TI  - Mouldable liquid-crystalline elastomer actuators with exchangeable covalent
      bonds.
AB  - Liquid-crystal elastomers (LCEs) are a class of actively moving polymers with
      remarkable practical potential for converting external stimuli into mechanical
      actuation. However, real-world applications of LCEs are lacking because
      macroscopic orientation of liquid-crystal order, which is required for reversible
      actuations, is hard to achieve in practice. Here we show that the processing
      bottleneck of LCEs can be overcome by introducing exchangeable links in place of
      permanent network crosslinks, a concept previously demonstrated for vitrimers.
      Liquid-crystal elastomers with exchangeable links (xLCEs) are mouldable, allow
      for easy processing and alignment, and can be subsequently altered through
      remoulding with different stress patterns, thus opening the way to practical xLCE
      actuators and artificial muscles. Surprisingly, instead of external-stress
      relaxation through the creep of non-liquid-crystal transient networks with
      exchangeable links, xLCEs develop strong liquid-crystal alignment as an
      alternative mechanism of mechanical relaxation. 

PMID- 24292423
TI  - Early MRI diagnostics for suspected scaphoid fractures subsequent to initial
      plain radiography.
AB  - AIM: In the United Kingdom, diagnostic management of patients presenting to
      emergency department with a scaphoid injury varies. Follow-up plain radiographs,
      after an initial inconclusive X-ray, are common practice. We optimised the
      diagnostic pathway for these patients by focusing on the most appropriate
      diagnostic modality and on minimising the time to follow-up diagnostics.
      MATERIALS AND METHODS: A baseline audit in the period 2008-2009 involving a total
      of 184 patients was conducted, and after the introduction of new local guidelines
      for scaphoid injury diagnostics, a follow-up audit involving 79 patients was
      undertaken in 2010-2012. RESULTS: In the original audit, 130 patients had only
      scaphoid radiographs, of which 23 underwent initial and follow-up X-rays, and 107
      initial-only radiographs. Of those 23, just one single patient (4%) displayed a
      scaphoid fracture. Others underwent three imaging procedures: initial
      radiographs, follow-up radiographs and either bone scan (41 patients) or MRI (13
      patients). A further 6/41 (15%) and 4/13 (31%) fractures were detected by bone
      scan and MRI, respectively. In the re-audit, when MRI replaced follow-up X-rays
      and bone scans, 7 out of 77 (9%) patients were diagnosed with scaphoid fracture.
      Time from initial plain radiograph to follow-up MRI was reduced from an original
      mean of 36 to 14 days during the re-audit period. CONCLUSION: The introduction of
      early MRI enhances scaphoid injury diagnostics and accelerates patient
      management. We therefore endorse the introduction of this approach on a wider
      scale through an update of the clinical guidelines for scaphoid injuries.

PMID- 24292424
TI  - Evaluation of the morphological changes in the mandible for dentate and totally
      edentate elderly population using cone-beam computed tomography.
AB  - PURPOSE: The loss of teeth considerably modifies the mandibular shape. The aim of
      this study was to compare the morphological changes in the mandible for dentate
      and totally edentate elderly subjects using cone-beam computed tomography.
      METHODS: In total, 50 cone-beam computed tomography patients (25 dentate, 25
      edentate) without any maxilla-mandibular dysmorphosis were analyzed
      retrospectively. Panoramic representations of the mandible with superimposed
      axial slices and cross-sectional slices were developed with the cone-beam
      computed tomography scans. Values of the mandibular cortical index, bone quality
      index, gonial angle, antegonial angle, antegonial depth and condyle angle in the
      left and right side were measured. RESULTS: There was a significant difference in
      the mandibular cortical index between the total edentate group and the dentate
      group in the left side of the mandible (p < 0.001). There was a significant
      difference in the bone quality index between the total edentate group and the
      dentate group in the right side and the left side (p < 0.001). There was a
      significant difference in the bone quality index between the right side and the
      left side (p < 0.005). When comparing gender, there was only a difference in the
      right side (p < 0.05). CONCLUSIONS: Our study concluded that the mandibular basal
      bone morphology changes as a consequence of tooth loss. Cone-beam computed
      tomography is shown to be a good tool in investigating and achieving these
      results.

PMID- 24292426
TI  - Concentrations of 90Sr in the tooth tissues 60 years after intake: results of TL
      measurements and applications for Techa River dosimetry.
AB  - This article focuses on the study of (90)Sr in the tooth tissues of Techa
      riverside residents 60 years after intake. The Techa River was contaminated by
      radioactive wastes in the 1950s. Contamination of the river system, including
      water, bottom sediment, floodplain soil, and grass, depended on the distance from
      the source of releases. Therefore, the average (90)Sr intake was different in
      different settlements located downstream the river. An additional factor
      influencing (90)Sr accumulation in the teeth is the rate of tissue mineralization
      at the time of intake which depended on the donor's age at the time of releases.
      Measurements of (90)Sr concentration in various dental tissues (enamel, crown,
      and root dentin) of 166 teeth were performed about 60 years after the main intake
      using the method of thermoluminescence passive beta detection. The paper presents
      the current levels of tooth tissue contamination, and the tooth-to-tooth
      variability of (90)Sr concentration in tooth tissues was assessed for the tissues
      which were matured at the time of massive liquid radioactive waste releases into
      the Techa River. A model describing the expected levels of (90)Sr in matured
      dental tissues depending on age and intake has been elaborated for the population
      under study. The results obtained will be used for calculation of internal dose
      in enamel and for interpretation of tooth doses measured by means of the electron
      paramagnetic resonance method, among the population of the Techa River region.

PMID- 24292425
TI  - Intensity-modulated and hypofractionated simultaneous integrated boost adjuvant
      breast radiation employing statics ports of tomotherapy (TomoDirect): a
      prospective phase II trial.
AB  - PURPOSE: To report the 1-year outcomes of a prospective phase II study on
      hypofractionated whole-breast intensity-modulated radiotherapy (IM-WBRT) with a
      simultaneous integrated boost (SIB) to the tumor bed delivered with static ports
      of tomotherapy (TomoDirect) (TD). METHODS: A prospective cohort of 82 patients
      was enrolled between 2011 and 2012. Treatment schedule consisted of 45 Gy/20
      fractions to the whole breast and 50 Gy/20 fractions to the surgical bed
      delivered concomitantly with TD over 4 weeks. A one-armed optimal two-stage
      Simon's design was selected to test the hypothesis that treatment modality under
      investigation would decrease acute skin toxicity over historical data using
      conventional fractionation and sequential boost. Primary endpoint was acute skin
      toxicity. Secondary endpoints included late toxicity, cosmesis, quality of life
      and local control. RESULTS: Median follow-up was 12 months (range 6-18). Maximum
      detected acute skin toxicity was G0 41 %; G1 53 %; G2 6 %; G3 <1 %. With two G2
      G3 acute skin toxicity events in the first stage and four in the second, the
      study fulfilled the requirements for the definition of the treatment approach
      under investigation as promising. Late skin toxicity was mild with no >G2 events.
      Cosmesis was good/excellent in 91 % of patients and fair/poor in 9 %. Quality of
      life was preserved over time, with the exception of fatigue, which was
      transiently increased. CONCLUSIONS: Hypofractionated IM-WBRT with a SIB to the
      tumor bed delivered with TD provides consistent clinical results and it is able
      to reduce acute skin toxicity rate over conventionally fractionated and
      sequential boost tomotherapy-based IM-WBRT.

PMID- 24292427
TI  - Work-related upper limb musculoskeletal disorders in pediatric minimally invasive
      surgery: a multicentric survey comparing laparoscopic and sils ergonomy.
AB  - PURPOSE: Surgeons are at risk for developing work-related musculoskeletal
      symptoms (WMS). The present study aims to compare laparoscopy and SILS ergonomy
      among pediatric surgeons. METHODS: A questionnaire formed by 17 questions was
      mailed to 14 pediatric surgeons, seven with a large experience in laparoscopy and
      seven in SILS. All surgeons completed the survey. The questionnaires were focused
      on the type of laparoscopic or SILS activity, location and type of pain, need for
      drugs and its physical consequences. Results were analyzed using chi(2) test.
      RESULTS: Results indicated a similar incidence of WMS with shoulder symptoms
      (>75%) in both groups. In laparoscopic group this pain is evident only after a
      long lasting procedure, while in SILS group the pain is present after each
      procedure performed. SILS surgeons used painkillers and other therapies
      statistically more frequently than laparoscopic group (chi(2) = 0.001).
      CONCLUSIONS: This study confirms there is a strong association between WMS and
      MIS surgery. The incidence of pain is similar in both groups. Pain was present
      only after long lasting procedures in laparoscopic group, while SILS surgeons
      have pain after each procedure performed. In addition SILS surgeons use more
      frequently painkillers and other therapies compared to laparoscopic surgeons. In
      conclusion, it seems that SILS has a worse ergonomy compared to laparoscopy.

PMID- 24292428
TI  - First- and second-sphere contributions to Fe(II) site activation by cosubstrate
      binding in non-heme Fe enzymes.
AB  - Non-heme Fe(II) enzymes exhibit a general mechanistic strategy where binding all
      cosubstrates opens a coordination site on the Fe(II) for O2 activation. This
      study shows that strong-donor ligands, steric interactions with the substrate and
      second-sphere H-bonding to the facial triad carboxylate allow for five-coordinate
      site formation in this enzyme superfamily.

PMID- 24292429
TI  - Enzyme-linked immunosorbent assay in analysis of deoxynivalenol: investigation of
      the impact of sample matrix on results accuracy.
AB  - Enzyme-linked immunosorbent assay (ELISA) represents a bioanalytical strategy
      frequently used for rapid screening of mycotoxin deoxynivalenol (DON) in cereals
      and derived products. Due to a considerable affinity of some anti-DON antibodies
      to structurally similar DON metabolites, such as DON-3-glucoside (DON-3-Glc) and
      3-acetyl-DON (3-ADON), a significant overestimation of DON concentrations may
      occur. A validation study of six commercial DON-dedicated ELISA kits, namely
      Ridascreen DON, Ridascreen FAST, DON, DON EIA, AgraQuant DON Assay, Veratox 5/5,
      and Veratox HS was carried out on wheat, barley, and malt matrices. Performance
      characteristics of all tested ELISAs were determined using aqueous solutions of
      DON, DON-3-Glc, and 3-ADON analytical standards, further with extracts of
      artificially spiked blank cereals, and finally with matrix-matched standards of
      all three compounds. In the final phase, the accuracy of data was assessed
      through a comparison of DON concentrations determined by particular ELISAs and
      reference ultra-high-performance liquid chromatography-tandem mass spectrometry
      method. For this purpose, both quality control materials and a comprehensive set
      of naturally and artificially contaminated samples of wheat, barley, and malt
      were analyzed. High cross-reactivities were proved for both DON-3-Glc and 3-ADON
      in the majority of examined assays, and moreover, a considerable contribution of
      some matrix components to overestimation of DON results was confirmed. 

PMID- 24292430
TI  - Reconstitution of supramolecular organization involved in energy metabolism at
      electrochemical interfaces for biosensing and bioenergy production.
AB  - How the redox proteins and enzymes involved in bioenergetic pathways are
      organized is a relevant fundamental question, but our understanding of this is
      still incomplete. This review provides a critical examination of the
      electrochemical tools developed in recent years to obtain knowledge of the
      intramolecular and intermolecular electron transfer processes involved in
      metabolic pathways. Furthermore, better understanding of the electron transfer
      processes associated with energy metabolism will provide the basis for the
      rational design of biotechnological devices such as electrochemical biosensors,
      enzymatic and microbial fuel cells, and hydrogen production factories. Starting
      from the redox complexes involved in two relevant bacterial chains, i.e., from
      the hyperthermophile Aquifex aeolicus and the acidophile Acidithiobacillus
      ferrooxidans, examination of protein-protein interactions using electrochemistry
      is first reviewed, with a focus on the orientation of a protein on an
      electrochemical interface mimic of a physiological interaction between two
      partners. Special attention is paid to current research in the electrochemistry
      of essential membrane proteins, which is one mandatory step toward the
      understanding of energy metabolic pathways. The complex and challenging
      architectures built to reconstitute a membrane-like environment at an electrode
      are especially considered. The role played by electrochemistry in the attempt to
      consider full bacterial metabolism is finally emphasized through the study of
      whole cells immobilized at electrodes as suspensions or biofilms. Before the
      performances of biotechnological devices can be further improved to make them
      really attractive, questions remain to be addressed in this particular field of
      research. We discuss the bottlenecks that need to be overcome in the future. 

PMID- 24292431
TI  - ICP-MS-based characterization of inorganic nanoparticles--sample preparation and
      off-line fractionation strategies.
AB  - Validated and easily applicable analytical tools are required to develop and
      implement regulatory frameworks and an appropriate risk assessment for engineered
      nanoparticles (ENPs). Concerning metal-based ENPs, two main aspects are the
      quantification of the absolute mass concentration and of the "dissolved" fraction
      in, e.g., (eco)toxicity and environmental studies. To provide information on
      preparative aspects and on potential uncertainties, preferably simple off-line
      methods were compared to determine (1) the total concentration of suspensions of
      five metal-based ENP materials (Ag, TiO2, CeO2, ZnO, and Au; two sizes), and (2)
      six methods to quantify the "dissolved" fraction of an Ag ENP suspension.
      Focusing on inductively coupled plasma-mass spectrometry, the total concentration
      of the ENP suspensions was determined by direct measurement, after acidification
      and after microwave-assisted digestion. Except for Au 10 nm, the total
      concentrations determined by direct measurements were clearly lower than those
      measured after digestion (between 61.1 % for Au 200 nm and 93.7 % for ZnO). In
      general, acidified suspensions delivered better recoveries from 89.3 % (ZnO) to
      99.3 % (Ag). For the quantification of dissolved fractions two filtration methods
      (ultrafiltration and tangential flow filtration), centrifugation and ion
      selective electrode were mainly appropriate with certain limitations, while
      dialysis and cloud point extraction cannot be recommended. With respect to
      precision, time consumption, applicability, as well as to economic demands,
      ultrafiltration in combination with microwave digestion was identified as best
      practice. 

PMID- 24292432
TI  - Analysis and accurate reconstruction of incomplete data in X-ray differential
      phase-contrast computed tomography.
AB  - X-ray differential phase-contrast computed tomography (DPC-CT) is a powerful
      physical and biochemical analysis tool. In practical applications, there are
      often challenges for DPC-CT due to insufficient data caused by few-view, bad or
      missing detector channels, or limited scanning angular range. They occur quite
      frequently because of experimental constraints from imaging hardware, scanning
      geometry, and the exposure dose delivered to living specimens. In this work, we
      analyze the influence of incomplete data on DPC-CT image reconstruction. Then, a
      reconstruction method is developed and investigated for incomplete data DPC-CT.
      It is based on an algebraic iteration reconstruction technique, which minimizes
      the image total variation and permits accurate tomographic imaging with less
      data. This work comprises a numerical study of the method and its experimental
      verification using a dataset measured at the W2 beamline of the storage ring
      DORIS III equipped with a Talbot-Lau interferometer. The numerical and
      experimental results demonstrate that the presented method can handle incomplete
      data. It will be of interest for a wide range of DPC-CT applications in medicine,
      biology, and nondestructive testing. 

PMID- 24292433
TI  - High-throughput, multiparameter analysis of single cells.
AB  - Heterogeneity of cell populations in various biological systems has been widely
      recognized, and the highly heterogeneous nature of cancer cells has been emerging
      with clinical relevance. Single-cell analysis using a combination of high
      throughput and multiparameter approaches is capable of reflecting cell-to-cell
      variability, and at the same time of unraveling the complexity and
      interdependence of cellular processes in the individual cells of a heterogeneous
      population. In this review, analytical methods and microfluidic tools commonly
      used for high-throughput, multiparameter single-cell analysis of DNA, RNA, and
      proteins are discussed. Applications and limitations of currently available
      technologies for cancer research and diagnostics are reviewed in the light of the
      ultimate goal to establish clinically applicable assays. 

PMID- 24292434
TI  - Detection of silver nanoparticles in parsley by solid sampling high-resolution
      continuum source atomic absorption spectrometry.
AB  - In this work, we present a fast and simple approach for detection of silver
      nanoparticles (AgNPs) in biological material (parsley) by solid sampling high
      resolution-continuum source atomic absorption spectrometry (HR-CS AAS). A novel
      evaluation strategy was developed in order to distinguish AgNPs from ionic silver
      and for sizing of AgNPs. For this purpose, atomisation delay was introduced as
      significant indication of AgNPs, whereas atomisation rates allow distinction of
      20-, 60-, and 80-nm AgNPs. Atomisation delays were found to be higher for samples
      containing silver ions than for samples containing silver nanoparticles. A
      maximum difference in atomisation delay normalised by the sample weight of 6.27
      +/- 0.96 s mg(-1) was obtained after optimisation of the furnace program of the
      AAS. For this purpose, a multivariate experimental design was used varying
      atomisation temperature, atomisation heating rate and pyrolysis temperature.
      Atomisation rates were calculated as the slope of the first inflection point of
      the absorbance signals and correlated with the size of the AgNPs in the
      biological sample. Hence, solid sampling HR-CS AAS was proved to be a promising
      tool for identifying and distinguishing silver nanoparticles from ionic silver
      directly in solid biological samples. 

PMID- 24292435
TI  - In vitro stability of free and glucuronidated cannabinoids in urine following
      controlled smoked cannabis.
AB  - Analyte stability is an important factor in urine test interpretation, yet
      cannabinoid stability data are limited. A comprehensive study of Delta(9)
      tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC
      (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide
      stabilities in authentic urine was completed. Urine samples after ad libitum
      cannabis smoking were pooled to prepare low and high pools for each study
      participant; baseline concentrations were measured within 24 h at room
      temperature (RT), 4  degrees C and -20  degrees C. Stability at RT, 4  degrees C
      and -20  degrees C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC
      glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT
      THCCOOH baseline concentrations were significantly higher than -20  degrees C,
      but not 4  degrees C baseline concentrations. After 1 week at RT, THCCOOH
      increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In
      RT low pool, total THCCOOH (THCCOOH + THCCOOH-glucuronide) was significantly
      lower after 1 week. At 4  degrees C, THCCOOH was stable 2 weeks, THCCOOH
      glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable
      frozen for 1 year, but 6 months high pool results were significantly higher than
      baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total
      THCCOOH was stable 6 months at 4  degrees C, and frozen 6 months (low) and 1 year
      (high). THC, cannabidiol and cannabinol were never detected in urine; although
      not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after 1
      week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and
      4  degrees C. Analysis should be conducted within 3 months if non-hydrolyzed
      THCCOOH or THCCOOH-glucuronide quantification is required. 

PMID- 24292436
TI  - Community psychiatry tracks for residents: a review of four programs.
AB  - Many psychiatry residency graduates end up practicing at least in part in
      community settings. However, declining funding and other issues prevent many
      residency programs from offering robust community psychiatry training to all of
      their residents. Accordingly, some residency programs have developed Community
      Psychiatry Tracks, with the goal of developing future leaders in public sector
      psychiatry. We cataloged US psychiatry residency programs offering Community
      Psychiatry Tracks by reviewing the literature and surveying training directors
      and members of the American Association of Community Psychiatrists. Authors from
      each of the four programs found to be actively offering such tracks describe
      their track curricula, from which we elucidated common and variable elements as
      well as strengths and weaknesses and then make recommendations for other programs
      wishing to start a track. A Community Psychiatry Track preliminarily appears to
      be a well-received way to offer enhanced Community Psychiatry training to
      interested residents, to recruit medical students to residency programs, to offer
      opportunities for collaboration between residents and faculty members, and to
      expand opportunities for scholarly work by residents. 

PMID- 24292438
TI  - Contrasting diversity dynamics of phoretic mites and beetles associated with
      vertebrate carrion.
AB  - Carrion is an ephemeral and nutrient-rich resource that attracts a diverse array
      of arthropods as it decomposes. Carrion-associated mites often disperse between
      animal carcasses using phoresy, the transport of one species by another. Yet few
      studies have contrasted the dynamics of mite assemblages with other insect taxa
      present at carrion. We examined and compared the changes in abundance, species
      richness and composition of mite and beetle assemblages sampled at kangaroo
      carcasses in a grassy eucalypt woodland at four different times over a 6-month
      period. We found that the majority of mites were phoretic, with the mesostigmatid
      genera Uroseius (Uropodidae), Macrocheles (Macrochelidae) and Parasitus
      (Parasitidae) the most abundant taxa (excluding astigmatid mites). Abundance and
      richness patterns of mites and beetles were very different, with mites reaching
      peak abundance and richness at weeks 6 and 12, and beetles at weeks 1 and 6. Both
      mites and beetles showed clear successional patterns via changes in species
      presence and relative abundance. Our study shows that mesostigmatid mite
      assemblages have a delay in peak abundance and richness relative to beetle
      assemblages. This suggests that differences in dispersal and reproductive traits
      of arthropods may contribute to the contrasting diversity dynamics of carrion
      arthropod communities, and further highlights the role of carrion as a driver of
      diversity and heterogeneity in ecosystems.

PMID- 24292437
TI  - Population ageing and healthcare expenditure projections: new evidence from a
      time to death approach.
AB  - BACKGROUND: Health care expenditure (HCE) is not distributed evenly over a
      person's life course. How much is spent on the elderly is important as they are a
      population group that is increasing in size. However other factors, such as death
      related costs that are known to be high, need be considered as well in any
      expenditure projections and budget planning decisions. OBJECTIVE: This article
      analyses, for the first time in Scotland, how expenditure projections for acute
      inpatient care are influenced when applying two different analytical approaches:
      (1) accounting for healthcare (HC) spending at the end of life and (2) accounting
      for demographic changes only. The association between socioeconomic status and HC
      utilisation and costs at the end of life is also estimated. METHODS: A
      representative, longitudinal data set is used. Survival analysis is employed to
      allow inclusion of surviving sample members. Cost estimates are derived from a
      two-part regression model. Future population estimates were obtained for both
      methods and multiplied separately by cost estimates. RESULTS: Time to death
      (TTD), age at death and the interaction between these two have a significant
      effect on HC costs. As individuals approach death, those living in more deprived
      areas are less likely to be hospitalised than those individuals living in the
      more affluent areas, although this does not translate into incurring
      statistically significant higher costs. Projected HCE for acute inpatient care
      for the year 2028 was approximately 7% higher under the demographic approach as
      compared to a TTD approach. CONCLUSION: The analysis showed that if death is
      postponed into older ages, HCE (and HC budgets) would not increase to the same
      extent if these factors were ignored. Such factors would be ignored if the
      population that is in their last year(s) of life were not taken into
      consideration when obtaining cost estimates.

PMID- 24292440
TI  - A tellurium-substituted Lindqvist-type polyoxoniobate showing high H(2) evolution
      catalyzed by tellurium nanowires via photodecomposition.
AB  - A new tellurium-substituted Lindqvist-type polyoxoniobate [H2TeNb5O19](5-) was
      synthesized as a tetramethylammonium salt. When irradiated with a Xe lamp, a
      water-methanol solution of this cluster showed exceptionally high H2-evolution
      activity suggesting cocatalysis by the hexaniobate cluster and metallic
      tellurium, both of which are formed as photodecomposition products. 

PMID- 24292439
TI  - Highly stereoselective biosynthesis of (R)-alpha-hydroxy carboxylic acids through
      rationally re-designed mutation of D-lactate dehydrogenase.
AB  - An NAD-dependent D-lactate dehydrogenase (D-nLDH) of Lactobacillus bulgaricus
      ATCC 11842 was rationally re-designed for asymmetric reduction of a homologous
      series of alpha-keto carboxylic acids such as phenylpyruvic acid (PPA), alpha
      ketobutyric acid, alpha-ketovaleric acid, beta-hydroxypyruvate. Compared with
      wild-type D-nLDH, the Y52L mutant D-nLDH showed elevated activities toward
      unnatural substrates especially with large substitutes at C-3. By the
      biocatalysis combined with a formate dehydrogenase for in situ generation of
      NADH, the corresponding (R)-alpha-hydroxy carboxylic acids could be produced at
      high yields and highly optical purities. Taking the production of chiral (R)
      phenyllactic acid (PLA) from PPA for example, 50 mM PPA was completely reduced to
      (R)-PLA in 90 min with a high yield of 99.0% and a highly optical purity (>99.9%
      e.e.) by the coupling system. The results presented in this work suggest a
      promising alternative for the production of chiral alpha-hydroxy carboxylic
      acids.

PMID- 24292441
TI  - Low mercury levels in marine fish from estuarine and coastal environments in
      southern China.
AB  - This study is the first comprehensive evaluation of total Hg and methylmercury
      (MeHg) concentrations in wild marine fish from an estuarine and a coastal
      ecosystem in southern China. A total of 571 fish from 54 different species were
      examined. Our results showed that the Hg levels were generally low in the fish,
      and the Hg levels were below 30 ng g(-1) (wet weight) for 82% of the samples,
      which may be related to the reduced size of the fish and altered food web
      structure due to overfishing. Decreased coastal wetland coverage and different
      carbon sources may be responsible for the habitat-specific Hg concentrations. The
      degree of biomagnification was relatively low in the two systems. 

PMID- 24292442
TI  - Risk assessment of polychlorinated biphenyls and heavy metals in soils of an
      abandoned e-waste site in China.
AB  - Risk assessment of abandoned e-waste recycling areas received little attention.
      Herein, we report the concentrations of 16 PCBs and 7 heavy metals in soils near
      an abandoned e-waste recycling plant in Taizhou, China. Our data showed that
      levels of tri-, tetra-, penta-, hexa-PCBs were 9.01, 5.56, 12.93, 3.13 mg/kg, and
      Pb, Cd, Cu were 6082.9, 42.3, 2364.2 mg/kg soil. Cd was the most prevalent
      contaminant with Nemerow index value of 44.3. Contaminants have been transported
      from the abandoned site to nearby areas. The ecology risk assessment based on the
      high toxicological effect in Chinese hamster ovary cells and earthworms showed
      that both PCBs and heavy metal residue pose high risk to the ecosystem. Hazard
      quotient showed that Pb, Cd, Hg and Cu pose high health risks for adults and
      children. Our results recommended a full examination of the risk and regulatory
      compliance of abandoned e-waste recycling areas in the future. 

PMID- 24292443
TI  - Organocatalyzed cascade reactions of carbohydrates - a direct access to C
      glycosides.
AB  - An organocatalyzed transformation to elongate unprotected carbohydrates is
      described. This operationally simple methodology is based on a Knoevenagel-oxa
      Michael cascade. This reaction is catalyzed by proline and DBU. Products were
      obtained with exceptional high degrees of stereoselectivity. 

PMID- 24292444
TI  - Ferredoxin-dependent glutamate synthase: involvement in ammonium assimilation in
      Haloferax mediterranei.
AB  - Glutamate synthase (GOGAT) is one of the two important enzymes involved in the
      ammonium assimilation pathway glutamine synthetase (GS)/GOGAT, which enables Hfx.
      mediterranei to thrive in media with low ammonium concentration or containing
      just nitrate as single nitrogen source. The gene coding for this enzyme, gltS,
      has been sequenced, analysed and compared with other GOGATs from different
      organisms from the three domains of life. According to its amino acid sequence,
      Hfx. mediterranei GOGAT displays high homology with those from other archaeal
      halophilic organisms and with the bacterial alpha-like subunit. Hfx. mediterranei
      GOGAT and GS expression was induced under conditions of ammonium restriction. The
      GOGAT protein was found to be a monomer with a molecular mass of 163.78 kDa,
      which is consistent with that estimated by gel filtration, 198 +/- 30 kDa. The
      enzyme is highly ferredoxin dependent: activity was only observed with one of the
      two different 2Fe-2S ferredoxins chromatographically isolated from Hfx.
      mediterranei. The enzyme also displayed typical halophilic behaviour, being fully
      stable, and producing maximal activity, at salt concentrations from 3 to 4 M
      NaCl, pH 7.5 and a temperature of 50  degrees C.

PMID- 24292445
TI  - Diversity and abundance of the arsenite oxidase gene aioA in geothermal areas of
      Tengchong, Yunnan, China.
AB  - A total of 12 samples were collected from the Tengchong geothermal areas of
      Yunnan, China, with the goal to assess the arsenite (AsIII) oxidation potential
      of the extant microbial communities as inferred by the abundance and diversity of
      the AsIII oxidase large subunit gene aioA relative to geochemical context.
      Arsenic concentrations were higher (on average 251.68 MUg/L) in neutral or
      alkaline springs than in acidic springs (on average 30.88 MUg/L). aioA abundance
      ranged from 1.63 * 10(1) to 7.08 * 10(3) per ng of DNA and positively correlated
      with sulfide and the ratios of arsenate (AsV):total dissolved arsenic (AsTot).
      Based on qPCR estimates of bacterial and archaeal 16S rRNA gene abundance, aioA
      harboring organisms comprised as much as ~15% of the total community.
      Phylogenetically, the major aioA sequences (270 total) in the acidic hot springs
      (pH 3.3-4.4) were affiliated with Aquificales and Rhizobiales, while those in
      neutral or alkaline springs (pH 6.6-9.1) were inferred to be primarily bacteria
      related to Thermales and Burkholderiales. Interestingly, aioA abundance at one
      site greatly exceeded bacterial 16S rRNA gene abundance, suggesting these aioA
      genes were archaeal even though phylogenetically these aioA sequences were most
      similar to the Aquificales. In summary, this study described novel aioA sequences
      in geothermal features geographically far removed from those in the heavily
      studied Yellowstone geothermal complex.

PMID- 24292446
TI  - Just another brick in the wall: unravelling the epigenetic mechanism underlying
      tumour initiation of testicular germ cell cancer.

PMID- 24292447
TI  - A phase II multicentre study of ziv-aflibercept in combination with cisplatin and
      pemetrexed in patients with previously untreated advanced/metastatic non-squamous
      non-small cell lung cancer.
AB  - BACKGROUND: This study evaluated the efficacy and safety of ziv-aflibercept in
      combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC).
      METHODS: This single arm, multicentre phase II trial enrolled patients with
      previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients
      received intravenous ziv-aflibercept 6 mg kg(-1), pemetrexed 500 mg m(-2), and
      cisplatin 75 mg m(-2), every 21 days for up to six cycles. Maintenance
      administration of ziv-aflibercept was to continue until disease progression,
      intolerable toxicity or other cause for withdrawal. The co-primary end points
      were objective response rate (ORR) and progression-free survival (PFS). Planned
      sample size was 72 patients. RESULTS: The study was closed prematurely because of
      three confirmed and two suspected cases of reversible posterior
      leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median
      age was 61.5 years; 55% were male, 86% Caucasian and 50% had Eastern Cooperative
      Oncology Group performance status (ECOG PS)=0. A median of four cycles of ziv
      aflibercept was administered. The most common treatment-emergent adverse events
      (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%)
      as the most common grade 3/4 TEAE. Of the 38 evaluable patients, ORR was 26% and
      median PFS was 5 months. CONCLUSION: Cases of RPLS had been observed in other
      studies in the ziv-aflibercept clinical development programme but the rate
      observed in this study was higher than previously observed. This might be related
      to declining renal function and/or hypertension. Although ORR and PFS were in
      accordance with most historical first-line NSCLC studies, this combination of ziv
      aflibercept/cisplatin/pemetrexed will not be further explored in NSCLC.

PMID- 24292448
TI  - Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from
      a follow-up study.
AB  - BACKGROUND: The BRCA1 and BRCA2 genes confer increased susceptibility to breast
      and ovarian cancer and to a spectrum of other cancers. There is controversy
      regarding the risk of colorectal cancer conferred by germline mutations in these
      two genes. METHODS: We followed 7015 women with a BRCA mutation for new cases of
      colorectal cancer. Incidence rates in carriers were compared with population
      specific incidence rates, and standardised incidence ratios (SIRs) were
      estimated. The expected numbers of cancers were computed by multiplying person
      years at risk by the appropriate age-, sex- and country-specific incidence rates
      from the five countries. RESULTS: Twenty-one incident colorectal cancer cases
      were observed among all mutation carriers, compared with 23.6 cases expected. The
      SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7)
      and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon
      cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both
      genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and
      above. CONCLUSION: The risk of colorectal cancer is increased in female carriers
      of BRCA1 mutations below the age of 50 years but not in women with BRCA2
      mutations or in older women.

PMID- 24292449
TI  - Tumour-site-dependent expression profile of angiogenic factors in tumour
      associated stroma of primary colorectal cancer and metastases.
AB  - BACKGROUND: Tumour-associated stroma has a critical role in tumour proliferation.
      Our aim was to determine a specific protein expression profile of stromal
      angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential
      biomarkers or new therapy targets. METHODS: Frozen tissue of primary colorectal
      cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected
      to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein
      expression of nine angiogenic cytokines and eight MMPs was analysed using a
      multiplex-based protein assay. RESULTS: We found a differential expression of
      several MMPs and angiogenic cytokines in tumour cells compared with adjacent
      tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal
      expression of MMPs and angiogenic cytokines. Univariate analysis identified
      stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and
      Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases
      as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived
      Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung
      metastases. CONCLUSION: Expression of MMPs and angiogenic cytokines in tumour
      cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived
      MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can
      be helpful to identify new agents for a targeted therapy in patients with
      colorectal cancer.

PMID- 24292450
TI  - Is lack of surgery for older breast cancer patients in the UK explained by
      patient choice or poor health? A prospective cohort study.
AB  - BACKGROUND: Older women have lower breast cancer surgery rates than younger
      women. UK policy states that differences in cancer treatment by age can only be
      justified by patient choice or poor health. METHODS: We investigate whether lack
      of surgery for older patients is explained by patient choice/poor health in a
      prospective cohort study of 800 women aged >=70 years diagnosed with operable
      (stage 1-3a) breast cancer at 22 English breast cancer units in 2010-2013. DATA
      COLLECTION: interviews and case note review. OUTCOME MEASURE: surgery for
      operable (stage 1-3a) breast cancer <90 days of diagnosis. Logistic regression
      adjusts for age, health measures, tumour characteristics, socio-demographics and
      patient's/surgeon's perceived responsibility for treatment decisions. RESULTS: In
      the univariable analyses, increasing age predicts not undergoing surgery from the
      age of 75 years, compared with 70-74-year-olds. Adjusting for health measures and
      choice, only women aged >=85 years have reduced odds of surgery (OR 0.18, 95% CI:
      0.07-0.44). Each point increase in Activities of Daily Living score (worsening
      functional status) reduced the odds of surgery by over a fifth (OR 0.23, 95% CI:
      0.15-0.35). Patient's role in the treatment decisions made no difference to
      whether they received surgery or not; those who were active/collaborative were as
      likely to get surgery as those who were passive, that is, left the decision up to
      the surgeon. CONCLUSION: Lower surgery rates, among older women with breast
      cancer, are unlikely to be due to patients actively opting out of having this
      treatment. However, poorer health explains the difference in surgery between 75
      84-year-olds and younger women. Lack of surgery for women aged >=85 years
      persists even when health and patient choice are adjusted for.

PMID- 24292453
TI  - Cyclometallated ruthenium complex-modified upconversion nanophosphors for
      selective detection of Hg2+ ions in water.
AB  - Upconversion detection nanocomposites were assembled for the selective
      luminescent detection of mercury ions in water. A hydrophobic cyclometallated
      ruthenium complex [Ru(II)(bpy)2(thpy)]PF6 (abbreviated as Ru1; bpy = 2,2'
      bipyridine and thpy = 2-(2-thienyl)pyridine) is employed as a chemodosimeter to
      assemble on amphiphilic polymer-coating upconversion nanophosphors (UCNPs) based
      on the hydrophobic-hydrophobic interaction. Upon addition of Hg(2+), the
      nanocomposite not only exhibits a remarkable color change from deep-red to
      yellow, but also an enhanced upconversion luminescence (UCL) emission by
      hindering the luminescent resonance energy transfer (LRET) process from the
      upconversion emission of UCNPs to Ru1. Using the ratiometric UCL emission as a
      detection signal, the detection limit of Hg(2+) for this nanoprobe in aqueous
      solution is 8.2 ppb, which is much lower than that (329 ppb) determined by UV/Vis
      technology. Such an Hg(2+)-tunable LRET process provides a general strategy for
      fabricating a water-soluble upconversion-based nanoprobe for some special
      analyte. 

PMID- 24292451
TI  - Evidence that active demethylation mechanisms maintain the genome of carcinoma in
      situ cells hypomethylated in the adult testis.
AB  - BACKGROUND: Developmental arrest of fetal germ cells may lead to neoplastic
      transformation and formation of germ cell tumours via carcinoma in situ (CIS)
      cells. Normal fetal germ cell development requires complete erasure and re
      establishment of DNA methylation. In contrast to normal spermatogonia, the genome
      of CIS cells remains unmethylated in the adult testis. We here investigated the
      possible active and passive pathways that can sustain the CIS genome
      hypomethylated in the adult testis. METHODS: The levels of 5-methyl-cytosine
      (5mC) and 5-hydroxy-methyl-cytosine (5hmC) in DNA from micro-dissected CIS cells
      were assessed by quantitative measurements. The expression of TET1, TET2,
      APOBEC1, MBD4, APEX1, PARP1, DNMT1, DNMT3A, DNMT3B and DNMT3L in adult testis
      specimens with CIS and in human fetal testis was investigated by
      immunohistochemistry and immunofluorescence. RESULTS: DNA from micro-dissected
      CIS cells contained very low levels of 5hmC produced by ten eleven translocation
      (TET) enzymes. CIS cells and fetal germ cells expressed the suggested initiator
      of active demethylation, APOBEC1, and the base excision repair proteins MBD4,
      APEX1 and PARP1, whereas TETs - the alternative initiators were absent. Both
      maintenance and de novo methyltransferases were detected in CIS cells.
      CONCLUSION: The data are consistent with the presence of an active DNA de
      methylation pathway in CIS cells. The hypomethylated genome of CIS cells may
      contribute to phenotypic plasticity and invasive capabilities of this testicular
      cancer precursor.

PMID- 24292452
TI  - Urinary EpCAM in urothelial bladder cancer patients: characterisation and
      evaluation of biomarker potential.
AB  - BACKGROUND: Epithelial cell adhesion molecule is overexpressed in bladder tumours
      and released from bladder cancer cells in vitro. We test the hypotheses that
      urinary EpCAM could act as a biomarker for primary bladder cancer detection and
      risk stratification. METHODS: Epithelial cell adhesion molecule was measured by
      ELISA in urine from 607 patients with primary bladder tumours and in urine from
      53 non-cancer controls. Mann-Whitney tests and ROC analyses were used to
      determine statistical significance and discrimination between non-cancer controls
      and different stages and grades of disease. Multivariable modelling and Kaplan
      Meier analyses were used to determine prognostic significance. The structure of
      urinary EpCAM was investigated by western blotting and mass spectrometry.
      RESULTS: Urinary EpCAM levels increase with stage and grade of bladder cancer.
      Alongside grade and stage, elevated urinary EpCAM is an independent indicator of
      poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality.
      The soluble form of EpCAM in urine is the extracellular domain generated by
      cleavage between ala243 and gly244. Further studies are required to define the
      influence of other urinary tract malignancies and benign urological conditions on
      urinary EpCAM. CONCLUSION: The extracellular domain of EpCAM is shed into urine
      by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer
      specific survival, and may be useful within a multi-marker panel for disease
      detection or as a stand-alone marker to prioritise the investigation and
      treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder
      cancer are worthy of further investigation, and may identify novel therapeutic
      targets.

PMID- 24292454
TI  - 2-Arylacetic anhydrides as ammonium enolate precursors.
AB  - Readily prepared 2-arylacetic anhydrides act as convenient ammonium enolate
      precursors in isothiourea (HBTM-2.1)-mediated catalytic asymmetric intermolecular
      Michael addition-lactonisation processes, giving diverse synthetic building
      blocks in good yield with high diastereo- and enantiocontrol (up to 98 : 2 dr and
      >99% ee). 

PMID- 24292456
TI  - Disinfection capacity of seven constructed wetlands and ponds.
AB  - The disinfection performance of three subsurface flow constructed wetlands (SSF),
      a free-water surface-constructed wetland and three ponds were investigated. They
      functioned as advanced treatment stage following treatment in a large municipal
      wastewater treatment plant equipped with nutrient removal. Despite low influent
      concentrations of 10(3.9)/100 mL, Escherichia coli underwent a reduction of 1.7
      (ditch) to 2.3 (sandy loamy SSF) orders of magnitude. After passing through these
      treatment plants E. coli was lowered sufficiently to within the permitted levels
      thus allowing it to be used in drip irrigation of fruits and vegetables. The
      change of seasons and hydraulic loading (in the range of 50-150 mm/day) as well
      as short-term overloadings did not impact the effluents' quality.

PMID- 24292457
TI  - Occurrence and fate of N-nitrosamines and their formation potential in three
      wastewater treatment plants in Japan.
AB  - N-nitrosamines are well known as carcinogens present in the environment. However,
      studies of the occurrence and fate of N-nitrosamines and their N-nitrosamine
      formation potential (FP) in wastewater treatment plants (WWTPs) are lacking.
      Therefore, the objectives of this study were to determine the occurrence of N
      nitrosamines in WWTPs, the FP of N-nitrosamines on chloramination during
      wastewater treatment, and the efficiency of FPNH2Cl reduction by biological
      treatment. Also, the residual FPNH2Cl in the final discharge was investigated.
      The efficiencies of removal of N-nitrosamines ranged from 35 to 94% (WWTP O;
      residential area), from 58 to 98% (WWTP E; industrial area), and from 58% to >99%
      (WWTP N; industrial area). In WWTP O, the rates of production of N
      nitrosodimethylamine (NDMA) (42%) and NDBA (58%) were the highest. In WWTP E,
      only NDBA (34%) was produced. In WWTP N, NPYR and NPIP (both >99%) were produced.
      NDMA FPNH2Cl values were very high in influent in all WWTPs. The efficiencies of
      removal of N-nitrosamine FPNH2Cl during biological treatment ranged from 20% to
      >99%, but there is no obvious explanation for this variability. Residual N
      nitrosamine FPNH2Cl ranged from 2 to 22 ng L(-1). Thus, N-nitrosamines could be
      produced in water purification or reclamation plants using discharge from WWTPs. 

PMID- 24292459
TI  - Urban drainage models--simplifying uncertainty analysis for practitioners.
AB  - There is increasing awareness about uncertainties in the modelling of urban
      drainage systems and, as such, many new methods for uncertainty analyses have
      been developed. Despite this, all available methods have limitations which
      restrict their widespread application among practitioners. Here, a modified Monte
      Carlo based method is presented that reduces the subjectivity inherent in typical
      uncertainty approaches (e.g. cut-off thresholds), while using tangible concepts
      and providing practical outcomes for practitioners. The method compares the
      model's uncertainty bands to the uncertainty inherent in each measured/observed
      datapoint; an issue that is commonly overlooked in the uncertainty analysis of
      urban drainage models. This comparison allows the user to intuitively estimate
      the optimum number of simulations required to conduct uncertainty analyses. The
      output of the method includes parameter probability distributions (often used for
      sensitivity analyses) and prediction intervals. To demonstrate the new method, it
      is applied to a conceptual rainfall-runoff model (MOPUS) using a dataset
      collected from Melbourne, Australia. 

PMID- 24292458
TI  - Restoration of two shallow, urban lakes using the phosphorus inactivation method 
      preliminary results.
AB  - This paper presents the initial environmental effects of polyaluminum chloride
      application on the water quality of two connected, shallow urban lakes in the
      Mazurian Lakeland, Poland. The water quality of Lake Domowe Duze (62 ha, mean
      depth 2.4 m) and Lake Domowe Male (11 ha, mean depth 2.8 m) in Szczytno did not
      improve after sewage discharge cutoff. Thus, local authorities decided to
      implement a restoration project involving the 3-year application of aluminum
      coagulant (26 g Al m(-2)) and manipulation of fish stocking. In 2010 and 2011,
      the first two stages of the project were conducted. After restoration measures,
      phosphorus concentration in water, chemical oxygen demand, chlorophyll 'a' and
      phytoplankton biomass decreased significantly compared to the control years. No
      long-term decrease of pH was obtained after aluminum application. Low
      concentrations of dissolved aluminum in a water column (below 0.2 mg L(-1) during
      technical operations) did not show any negative effects on aquatic fauna. 

PMID- 24292460
TI  - Modelling of percolation rate of stormwater from underground infiltration
      systems.
AB  - Underground or surface stormwater storage tank systems that enable the
      infiltration of water into the ground are basic elements used in Sustainable
      Urban Drainage Systems (SUDS). So far, the design methods for such facilities
      have not taken into account the phenomenon of ground clogging during stormwater
      infiltration. Top layer sealing of the filter bed influences the infiltration
      rate of water into the ground. This study presents an original mathematical model
      describing changes in the infiltration rate variability in the phases of filling
      and emptying the storage and infiltration tank systems, which enables the
      determination of the degree of top ground layer clogging. The input data for
      modelling were obtained from studies conducted on experimental sites on objects
      constructed on a semi-technological scale. The experiment conducted has proven
      that the application of the model developed for the phase of water infiltration
      enables us to estimate the degree of module clogging. However, this method is
      more suitable for reservoirs embedded in more permeable soils than for those
      located in cohesive soils. 

PMID- 24292461
TI  - Start-up of a granular sludge sequencing batch reactor for the treatment of 2,4
      dichlorophenol-contaminated wastewater.
AB  - In this study, a granular sludge sequencing batch reactor (GSBR) was started-up
      for the biological aerobic treatment of wastewater containing highly toxic 2,4
      dichlorophenol (2,4-DCP), in presence of readily biodegradable sodium acetate
      (NaAc) as the growth substrate. Different influent concentrations of NaAc (420
      800 mg/L) and 2,4-DCP (0-20 mg/L), as well as different operating conditions
      (i.e. cycle length), were tested in order to determine the optimal strategy for
      successful GSBR start-up: stable granulation and complete 2,4-DCP removal were
      achieved only when high NaAc influent concentration and volumetric organic
      loading rates (800 mg/L and 1.9 kgCOD/(m(3).d), respectively), prolonged reaction
      phase (cycle time of 4 hours) and gradual increase of 2,4-DCP concentration in
      the influent were applied, thus providing useful information for process
      optimization in view of future scale-up. Granules were initially colonized by
      fungi which progressively disappeared during the start-up process, and complete
      2,4-DCP removal was mostly due to bacterial activity, in particular
      Betaproteobacteria, as shown by fluorescence in situ hybridization (FISH). 

PMID- 24292462
TI  - Adsorption of chloro-anilines from solution by modified peanut husk in fixed-bed
      column.
AB  - Natural peanut husk (NPH) modified with hexadecyl trimethyl ammonium bromide
      (CTAB) was used as adsorbent to remove 2,5-dimethoxy-4-chloroaniline (DMCH) from
      solution in a fixed-bed column. Fourier transform infrared spectroscopy analysis
      and X-ray fluorescence of NPH and modified peanut husk (MPH) showed that CTAB had
      been introduced onto the surface of NPH. The effects of flow rate and bed depth
      on breakthrough curves were studied. The Thomas model and the Yan model were
      selected to fit the column adsorption data and the results showed that the Yan
      model was better at predicting the breakthrough curves. The adsorption quantity
      was up to 6.46 mg/g according to the Yan model. The bed depth service time model
      was used to calculate the critical bed depth from experimental data and it was
      directly related to flow rate. As a low-cost adsorbent, MPH is promising for the
      removal of DMCH from solution. 

PMID- 24292463
TI  - Catchment-scale evaluation of pollution potential of urban snow at two
      residential catchments in southern Finland.
AB  - Despite the crucial role of snow in the hydrological cycle in cold climate
      conditions, monitoring studies of urban snow quality often lack discussions about
      the relevance of snow in the catchment-scale runoff management. In this study,
      measurements of snow quality were conducted at two residential catchments in
      Espoo, Finland, simultaneously with continuous runoff measurements. The results
      of the snow quality were used to produce catchment-scale estimates of areal snow
      mass loads (SML). Based on the results, urbanization reduced areal snow water
      equivalent but increased pollutant accumulation in snow: SMLs in a medium-density
      residential catchment were two- to four-fold higher in comparison with a low
      density residential catchment. The main sources of pollutants were related to
      vehicular traffic and road maintenance, but also pet excrement increased
      concentrations to a high level. Ploughed snow can contain 50% of the areal
      pollutant mass stored in snow despite its small surface area within a catchment. 

PMID- 24292464
TI  - Characterization of polyhydroxyalkanoate-producing bacteria isolated from sludge
      of commercial pig farms for producing methyl esters.
AB  - The objectives of this work were to isolate and characterize the
      polyhydroxyalkanoate (PHA) producing bacteria in enriched piggery sludge and make
      methyl esters from PHA for industrial applications. The strain ECAe24 isolated
      from piggery sludge with the highest PHA production was selected to produce PHA
      and then methyl ester by trans-esterification using glucose as substrate under
      mesophilic conditions. The final product after trans-esterification consisted of
      approximately 75.39% of fatty acid methyl ester and was identified as decanoic
      acid-3-hydroxy-methyl ester, octanoic acid-3-hydroxy-methyl ester, and some other
      contents. The novelty of this study is to use PHA-producing bacteria from piggery
      sludge to make fatty acid methyl esters which can be used as materials for
      producing biodiesel from piggery wastes. 

PMID- 24292465
TI  - Visible light-degradation of azo dye methyl orange using TiO2/beta-FeOOH as a
      heterogeneous photo-Fenton-like catalyst.
AB  - In this study, a novel TiO2/beta-FeOOH composite photocatalyst was synthesized by
      a hydrothermal method. X-ray diffraction, Fourier transform infrared spectrum, UV
      vis diffuse reflectance spectra and scanning electron microscopy (SEM) were used
      to characterize the composite photocatalyst. The photocatalytic activity of the
      prepared composite photocatalyst was evaluated in a heterogeneous photo-Fenton
      like process using methyl orange (MO) as target pollutant. The TiO2/beta-FeOOH
      composites exhibited higher photocatalytic activity than pure beta-FeOOH and TiO2
      under visible-light irradiation. The enhanced photocatalytic activity can be
      ascribed to the formation of TiO2/beta-FeOOH heterostructure, which plays an
      important role in expanding the photoactivity to the visible light region and in
      effectively prolonging the lifetime of photoinduced electrons and holes. Further
      investigation revealed that the 25TiO2/beta-FeOOH composite synthesized with the
      TiO2/Fe(3+) in a mole ratio of 25:75 showed the highest catalytic activity. 

PMID- 24292466
TI  - Trialling urine diversion in Australia: technical and social learnings.
AB  - This paper discusses a urine diversion (UD) trial implemented within the
      institutional setting of the University of Technology Sydney that sought to
      identify key issues for public UD and reuse systems at scale in the Australian
      urban context. The trial was novel in its transdisciplinary action research
      approach, that included consideration of urine diverting toilets (UDTs) as socio
      technical systems where interactions between users' practices and perceptions and
      the performance of the technology were explored. While the study explored a broad
      range of issues that included urine transport, reuse, and regulations, amongst
      others, the boundary of the work presented in this paper is the practicalities of
      UD practice within public urban buildings. Urine volume per urinal use, an
      important metric for sizing tanks for collecting urine from waterless urinal
      systems in commercial buildings, was also estimated. The project concluded that
      current UDTs are unsuitable to public/commercial spaces, but waterless urinals
      have a key role. 

PMID- 24292467
TI  - Performance characterisation of a constructed wetland.
AB  - Performance of a constructed wetland is commonly reported as being variable due
      to the site specific nature of influential factors. This paper discusses the
      outcomes from an in-depth study which characterised the treatment performance of
      a wetland based on the variation in the runoff regime. The study included a
      comprehensive field monitoring of a well-established constructed wetland in Gold
      Coast, Australia. Samples collected at the inlet and outlet were tested for Total
      Suspended Solids (TSS), Total Nitrogen (TN) and Total Phosphorus (TP). Pollutant
      concentrations in the outflow were found to be consistent irrespective of the
      variation in inflow water quality. The analysis revealed two different treatment
      characteristics for events with different rainfall depths. TSS and TN load
      reduction was found to be strongly influenced by the hydraulic retention time
      where performance was relatively superior for rainfall events below the design
      event. For small events, treatment performance was higher at the beginning of the
      event and gradually decreased during the course of the event. For large events,
      the treatment performance was comparatively poor at the beginning and improved
      during the course of the event. The analysis also confirmed the variable
      treatment trends for different pollutant types. 

PMID- 24292468
TI  - Removal of ecotoxicity and COD from tank truck cleaning wastewater.
AB  - Tank truck cleaning (TTC) activities generate highly complex wastewater. In a
      previous study, we found that a significant ecotoxic effect was still present in
      biologically treated TTC wastewater. The aim of the present study was therefore
      to investigate the removal of acute toxicity from TTC wastewater by a sequence of
      technologies routinely applied for industrial wastewater. Acute toxicity was
      assayed with the widely applied and standardized Vibrio fischeri bioluminescence
      inhibition test. During a 5-month period, raw wastewater was grab-sampled from a
      full-scale TTC company and treated by the different unit operations on a
      laboratory scale. Chemical pretreatment of the wastewater by coagulation with
      FeCl3 removed approx. 38% of the influent chemical oxygen demand (COD) and
      reduced the bioluminescence inhibition by 8%. Biological treatment with activated
      sludge subsequently removed another 77% of the remaining COD. This treatment step
      also reduced the bioluminescence inhibition but the removal efficiency varied
      strongly from 5 to 92% for the different samples. Powdered activated carbon
      almost completely removed the remaining COD and inhibition in all samples. The
      results suggest that conventional technologies did not suffice for complete
      removal of toxicity from TTC wastewater, and that advanced wastewater treatment
      technologies such as activated carbon are required for a satisfactory
      detoxification. 

PMID- 24292469
TI  - Sorption of thallium(I) ions by peat.
AB  - The increasing industrial use of thallium has raised the need for removal of this
      highly toxic element from wastewater. Thallium is more toxic than cadmium,
      copper, zinc, lead and mercury and as it is easily accumulated in humans, animals
      and plants, it poses a threat to both the environment and human health. Peat has
      been used as an effective, relatively cheap and easily available sorbent to treat
      waters containing heavy metals. In this study, peat was characterized and used as
      sorbent for the removal of Tl(I) ions from aqueous solution. The effect of
      initial Tl(I) concentration, pH, contact time, temperature and ionic strength was
      studied in batch mode. The maximum sorption capacity of peat reached 24.14 mg/g
      at 20  degrees C and initial Tl(I) concentration of 500 mg/L. Sorption capacity
      was found to be pH dependent and maximum uptake occurred at pH 10. Kinetic data
      revealed that sorption was relatively rapid - 82.8% of Tl(I) ions were sorbed in
      the first 10 min. The kinetics of sorption was analyzed using pseudo-first order
      and pseudo-second order models. Results show that peat can be used as an
      effective sorbent to remove Tl(I) ions from aqueous solutions. 

PMID- 24292470
TI  - Toxicity reduction and biodegradability enhancement of cork processing
      wastewaters by ozonation.
AB  - Biodegradability enhancement and detoxification of cork boiling wastewater (CBW)
      are required for the successful implementation of biological treatment options.
      We studied the possibility of achieving these goals through ozonation pre
      treatment by experimenting on the effect of ozone dose and pH. The CBW used had a
      pH of 5.81, a chemical oxygen demand (COD) of 1,865 mg L(-1), a biochemical
      oxygen demand (BOD5) of 498 mg L(-1) and total phenol (TP) and tannin compounds
      concentrations of 523 and 399 mg L(-1), respectively. The ozone doses ranged from
      0.27 to 2.63 for the O3(applied)/COD0 ratios with samples at natural pH and set
      to 3.33 and 9.96. Ozonation allowed the BOD20/COD ratio (biodegradability index)
      to increase from 0.37 to 0.63 and a toxicity reduction from 3.08 to 1.24 TU
      (Microtox). The corresponding removals obtained were 15.2-62.0%, 38.4-83.2% and
      56.7-92.1% for COD, TP and colour, respectively. The best outcome of ozonation
      pre-treatment requires O3(applied)/COD0 ratios over 1.5 and an acid pH. The
      increase of TP removals with ozone dose at acid pH led to biodegradability
      enhancement and CBW detoxification. However, for similar conditions the highest
      COD removals were obtained at alkaline pH due to the hydroxyl radicals' high
      oxidation ability but lack of selectivity. 

PMID- 24292471
TI  - The treatment of zinc-cyanide electroplating rinse water using an
      electrocoagulation process.
AB  - This paper investigates the treatment of zinc-cyanide electroplating rinse water
      using an electrocoagulation process (ECP). The effects of operating parameters
      such as electrode material, current density (2.5-40 A/m(2)), operating time (0-60
      min), initial pH (5-12) and electrode connection mode (monopolar parallel (MP-P),
      monopolar series and bipolar series) on the ECP were evaluated to find the
      optimum operating conditions. At 20 A/m(2), 60 min, the highest removal
      efficiencies were obtained with 85 and 99% for Fe and 64 and 33% for Al
      electrodes, for cyanide and zinc, respectively. The optimum operating conditions
      were found to be 30 A/m(2) and 40 min, for the Fe electrode at the original pH
      (9.5) of the rinse water. Considering efficiency and economy, the MP-P connection
      mode was determined as the optimum connection mode. 

PMID- 24292472
TI  - Biological Cr(VI) removal using bio-filters and constructed wetlands.
AB  - The bioreduction of hexavalent chromium from aqueous solution was carried out
      using suspended growth and packed-bed reactors under a draw-fill operating mode,
      and horizontal subsurface constructed wetlands. Reactors were inoculated with
      industrial sludge from the Hellenic Aerospace Industry using sugar as substrate.
      In the suspended growth reactors, the maximum Cr(VI) reduction rate (about 2 mg/L
      h) was achieved for an initial concentration of 12.85 mg/L, while in the attached
      growth reactors, a similar reduction rate was achieved even with high initial
      concentrations (109 mg/L), thus confirming the advantage of these systems. Two
      horizontal subsurface constructed wetlands (CWs) pilot-scale units were also
      built and operated. The units contained fine gravel. One unit was planted with
      common reeds and one was kept unplanted. The mean influent concentrations of
      Cr(VI) were 5.61 and 5.47 mg/L for the planted and unplanted units, respectively.
      The performance of the planted CW units was very effective as mean Cr(VI) removal
      efficiency was 85% and efficiency maximum reached 100%. On the contrary, the
      unplanted CW achieved very low Cr(VI) removal with a mean value of 26%. Both
      attached growth reactors and CWs proved efficient and viable means for Cr(VI)
      reduction. 

PMID- 24292473
TI  - Hygienization of sludge through anaerobic digestion at 35, 55 and 60  degrees C.
AB  - Legislation in Sweden and the European Union concerning the use of sewage sludge
      in agriculture is under revision and future concentration limits for pathogens in
      treated sludge are likely to be expected. The aim of this study was to evaluate
      the hygienization of Salmonella, Escherichia coli, Enterococcus and Clostridium
      perfringens through continuous anaerobic digestion at 35, 55 or 60  degrees C, as
      well as to investigate process stability and methane production at 60  degrees C.
      The results indicated that digestion at 55 or 60  degrees C with a minimum
      exposure time of 2 h resulted in good reduction of Salmonella, E. coli and
      Enterococcus and that anaerobic digestion could thus be used to reach the
      concentration limits suggested for the EU, as well as Sweden. Furthermore, stable
      continuous anaerobic digestion of sludge was achieved at 60  degrees C, albeit
      with 10% less methane production compared to digestion at 35 and 55  degrees C. 

PMID- 24292474
TI  - Adsorption of methylene blue and Congo red from aqueous solution by activated
      carbon and carbon nanotubes.
AB  - This study was conducted to determine the adsorption removal of dyes by powdered
      activated carbon (PAC, Norit) and multi-walled carbon nanotubes (MWCNTs, Chinese
      Academy of Science) from an aqueous solution. Methylene blue (MB) and Congo red
      (CR) were selected as model compounds. The adsorbents tested have a high surface
      area (PAC 835 m(2)/g, MWCNTs 358 m(2)/g) and a well-developed porous structure
      which enabled the effective treatment of dye-contaminated waters and wastewaters.
      To evaluate the capacity of PAC and MWCNTs to adsorb dyes, a series of batch
      adsorption experiments was performed. Both adsorbents exhibited a high adsorptive
      capacity for MB and CR, and equilibrium data fitted well with the Langmuir model,
      with the maximum adsorption capacity up to 400 mg/g for MB and 500 mg/g for CR.
      The separation factor, RL, revealed the favorable nature of the adsorption
      process under experimental conditions. The kinetics of adsorption was studied at
      various initial dye concentrations and solution temperatures. The pseudo-second
      order model was used for determining the adsorption kinetics of MB and CR. The
      data obtained show that adsorption of both dyes was rapid in the initial stage
      and followed by slower processing to reach the plateau. The uptake of dyes
      increased with contact time, irrespective of their initial concentration and
      solution temperature. However, changes in the solution temperature did not
      significantly influence dye removal. 

PMID- 24292475
TI  - Effect of primary particle size on colloidal stability of multiwall carbon
      nanotubes.
AB  - Multiwall carbon nanotubes (MWCNTs) are one type of nanoparticles that have
      various special properties and potential applications. Due to their increasing
      production and potential toxicological effects, the environmental behavior and
      transport of MWCNTs have become important research topics. Particle size is one
      of the important properties of nanoparticles, yet its effects on MWCNT
      environmental behaviors have not been fully investigated. In this study, we
      tested how the length of MWCNTs influenced their settling in the presence of
      Na(+) and/or natural organic matter (NOM), and postulated the governing
      mechanisms. The results showed that when adding Na(+) the shorter MWCNTs
      exhibited preferential aggregation and settling. One possible reason could be
      that shorter MWCNTs possess larger specific surface area and consequently
      stronger attraction forces. However, NOM strongly mitigated such aggregation, and
      helps to disperse MWCNTs regardless of their length and aqueous conditions. 

PMID- 24292476
TI  - Physical-chemical characterization of sludge and granular materials from a
      vertical flow constructed wetland for municipal wastewater treatment.
AB  - The use of vertical flow constructed wetlands (VFCWs) is well developed in France
      and other countries for the treatment of wastewaters from small communities. The
      patented Azoe(r) process has been developed by a French company, SCIRPE, in order
      to improve denitrification and phosphorus removal as compared to classical VFCWs.
      It includes a biological trickling filter pretreatment followed by two stages of
      partially flooded VFCW. The performances of partially flooded VFCW are well
      demonstrated for the removal of organic matter and nitrogen. The system is now
      being considered for phosphorus removal as well. In this article, sludge and
      granular materials sampled from the filters of a municipal plant where the
      Azoe(r) system has been operated for 8 years were analyzed in order to provide
      data that may contribute to a better understanding of the dynamics of phosphorus
      retention. Elemental analyses showed that phosphorus was predominantly captured
      in the sludge layer accumulated at the surface of the first stage. The
      progressive mineralization of the sludge over time was also clearly highlighted.
      The phosphate phases were mainly associated with iron and calcium. The transport
      of phosphorus via the migration of fine particles through the porous medium in
      the first stage was also observed. 

PMID- 24292477
TI  - Material selection for a constructed wetroof receiving pre-treated high strength
      domestic wastewater.
AB  - A constructed wetroof (CWR) is defined in this study as the combination of a
      green roof and a constructed wetland: a shallow wastewater treatment system
      placed on the roof of a building. The foremost challenge of such CWRs, and the
      main aim of this investigation, is the selection of an appropriate matrix capable
      of assuring the required hydraulic retention time, the long-term stability and
      the roof load-bearing capacity. Six substrata were subjected to water dynamics
      and destructive tests in two testing-tables. Among all the materials tested, the
      substratum configuration composed of sand, light expanded clay aggregates,
      biodegradable polylactic acid beads together with stabilization plates and a turf
      mat is capable of retaining the water for approximately 3.8 days and of providing
      stability (stabilization plates) and an immediate protection (turf mat) to the
      system. Based on those results, a full-scale CWR was built, which did not show
      any physical deterioration after 1 year of operation. Preliminary wastewater
      treatment results on the full-scale CWR suggest that it can highly remove main
      wastewater pollutants (e.g. chemical oxygen demand, PO4(3-)-P and NH4(+)-N). The
      results of these tests and practical design considerations of the CWR are
      discussed in this paper. 

PMID- 24292478
TI  - Performance assessment of pilot horizontal sub-surface flow constructed wetlands
      for removal of diesel from wastewater by Scirpus grossus.
AB  - One of the appropriate development technology options for the treatment of
      wastewater contaminated with diesel is constructed wetlands (CWs). Throughout 72
      days of exposure, sampling was carried out for monitoring of physical parameters,
      plant growth and the efficiency of total petroleum hydrocarbon (TPH) removal, as
      an indication for diesel contamination, to assess the pilot-scale performance.
      Four pilot CWs with a horizontal sub-surface flow system were applied using the
      bulrush of Scirpus grossus. The CWs were loaded with different diesel
      concentrations of 0, 0.1, 0.2 and 0.25% (Vdiesel/Vwater). The TPH removal
      efficiencies were 82, 71, and 67% at the end of 72 days for diesel concentrations
      of 0.1, 0.2, and 0.25% respectively. In addition, the high removal efficiency of
      total suspended solids and chemical oxygen demand (COD) were 100 and 75.4%
      respectively, for a diesel concentration of 0.1%. It was concluded that S.
      grossus is a potential plant that can be used in a well-operated CW for restoring
      0.1% diesel-contaminated water. 

PMID- 24292479
TI  - Photodegradation of chlorpyrifos in water by UV/H2O2 treatment: toxicity
      evaluation.
AB  - Chlorpyrifos (CP) is an organophosphorus pesticide widely used in agriculture.
      Due to its toxicity, it has been necessary to develop a treatment to eliminate
      the environmental wastes generated by this substance. The combination of UV
      radiation and hydrogen peroxide seemed an interesting option to reduce the
      concentration of CP in water, as it has proved to be a simple and effective
      method to degrade other similar pesticides. The purpose of this work is to study
      the effect of different initial concentrations of H2O2 on the degradation of
      commercial CP in water using UV/H2O2. Conversions of 93% were achieved in 20 min
      with 450 mg L(-1) of H2O2 initial concentration (0.16 mg of CP degraded per mg of
      H2O2 consumed). The total organic carbon analysis showed interesting
      mineralization values, reaching a 70% conversion after 4 h of reaction. In
      addition, this degradation procedure leads to a clear reduction of the toxicity
      of the reaction mixture over Vibrio fischeri. 

PMID- 24292480
TI  - Surface coating with Ca(OH)2 for improvement of the transport of nanoscale zero
      valent iron (nZVI) in porous media.
AB  - A novel thermal deposition method was developed to coat Ca(OH)2 on the surface of
      nanoscale zero-valent iron (nZVI). The nZVI particles with the Ca(OH)2 coating
      layer, nZVI/Ca(OH)2, had a clear core-shell structure based on the transmission
      electron microscopy observations, and the Ca(OH)2 shell was identified as an
      amorphous phase. The Ca(OH)2 coating shell would not only function as an
      effective protection layer for nZVI but also improve the mobility of nZVI in
      porous media for its use in environmental decontamination. A 10% Ca/Fe mass ratio
      was found to result in a proper thickness of the Ca(OH)2 shell on the nZVI
      surface. Based on the filtration tests in sand columns, the Ca(OH)2-based surface
      coating could greatly improve the mobility and transport of nZVI particles in
      porous media. In addition, batch experiments were conducted to evaluate the
      reactivity of Ca(OH)2-coated nZVI particles for the reduction of Cr(VI) and its
      removal from water. 

PMID- 24292481
TI  - Separation of hydrophobic organic compound from surfactant solutions with
      activated carbon in a fixed bed.
AB  - The adsorption behavior of phenanthrene (PHE) in Triton X-100 (TX100) solutions
      with fixed activated carbon (AC) bed was studied to recover the surfactant. The
      effect of various parameters like bed depths, flow rates, influent TX100
      concentration, and influent PHE concentration were investigated. The breakthrough
      time of both TX100 and PHE increased with the increase of bed height and decrease
      of flow rate and influent concentration. In the case of fixed length, a lower
      flow rate, higher concentration of TX100, and lower concentration of PHE will
      benefit the longer effective surfactant recovery time. The adsorption data were
      integrated into bed depth service time models. The height of exchange zone of
      TX100 should be much shorter than that of PHE, which provides conditions to
      separate the hydrophobic organic compound from surfactant solutions with AC in a
      fixed bed. It is likely that the adsorption process is controlled by hydrophobic
      interaction. 

PMID- 24292482
TI  - Correct manipulation method of MBR operating parameters in membrane fouling
      studies.
AB  - In this study, various parameter manipulation methods, variable sludge retention
      time (SRT)-variable mixed liquor suspended solids (MLSS) concentration, constant
      SRT-variable MLSS concentration and variable SRT-constant MLSS concentration,
      were compared based on the interrelationships among the following membrane
      bioreactor operating parameters: SRT, food to microorganisms (biomass) (F/M)
      ratio, MLSS concentration, volumetric organic loading rate (OLR) and membrane
      flux. Although it is the most applied method, concurrent change of SRT (or F/M
      ratio) and MLSS concentration is not a good parameter manipulation method because
      it causes unnecessary changes in many other parameters such as viscosity, oxygen
      transfer efficiency and oxygen utilization rate. The method of constant SRT
      variable MLSS concentration has similar disadvantages to the method of variable
      SRT-variable MLSS concentration. The best alternative parameter manipulation
      method to study membrane fouling is the method of variable SRT-constant MLSS
      concentration because this method eliminates unnecessary changes in other
      parameters. In addition, while changing OLR or hydraulic retention time (HRT),
      contrary to the common application, membrane flux should be kept constant because
      any change in flux overrides changes in other parameters. Accordingly, required
      changes in OLR or HRT should be made by adjusting membrane area rather than
      membrane flux. 

PMID- 24292483
TI  - The effect of several parameters on catalytic denitrification of water by the use
      of H2 in the presence of O2 over metal supported catalysts.
AB  - The present paper involves a detailed study of the selective catalytic reduction
      of nitrates in aqueous mediums by the use of H2 in the presence of O2 over
      monometallic and bimetallic supported catalysts. In this study, an attempt has
      been made to improve the denitrification efficiency (XNO3(-), SN2) of several
      catalysts by regulating some experimental parameters that are involved in the
      process. Therefore, the effects of the type of reactor (semi-batch reactor vs
      continuous flow reactor), the nature of the active phase (Pd, Cu, and Pd-Cu) and
      the particle size of gamma-Al2O3 spheres (particle diameter = 1.8 mm and 3 mm) on
      catalytic activity and reaction selectivity, as well as the adsorption capacity
      of gamma-Al2O3 spheres for nitrates, were examined. As the review indicates, most
      of the research has so far been conducted on batch or semi-batch reactors. This
      study successfully demonstrates the benefits of using a continuous flow reactor
      in terms of catalytic activity (XNO3(-), %) and reaction selectivity (SN2, %).
      Another important aspect of this study is the crucial role of bimetallic Pd-Cu
      clusters for the prevention of NH4(+) formation. Moreover, the use of 1.8 mm
      diameter gamma-Al2O3 spheres as a support was proved to significantly enhance the
      catalytic performance of bimetallic Pd-Cu catalysts towards nitrate reduction
      compared to 3 mm diameter gamma-Al2O3 spheres. This difference may be attributed
      to mass (NO3(-), OH(-)) transfer effects (external mass transfer phenomena). 

PMID- 24292484
TI  - Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their
      progeny.
AB  - Although Lgr5(+) intestinal stem cells have been expanded in vitro as organoids,
      homogeneous culture of these cells has not been possible thus far. Here we show
      that two small molecules, CHIR99021 and valproic acid, synergistically maintain
      self-renewal of mouse Lgr5(+) intestinal stem cells, resulting in nearly
      homogeneous cultures. The colony-forming efficiency of cells from these cultures
      is ~100-fold greater than that of cells cultured in the absence of CHIR99021 and
      valproic acid, and multilineage differentiation ability is preserved. We made use
      of these homogeneous cultures to identify conditions employing simultaneous
      modulation of Wnt and Notch signaling to direct lineage differentiation into
      mature enterocytes, goblet cells and Paneth cells. Expansion in these culture
      conditions may be feasible for Lgr5(+) cells from the mouse stomach and colon and
      from the human small intestine. These methods provide new tools for the study and
      application of multiple intestinal epithelial cell types.

PMID- 24292486
TI  - Instrument intercomparison in the high-energy mixed field at the CERN-EU
      reference field (CERF) facility.
AB  - This paper discusses an intercomparison campaign performed in the mixed radiation
      field at the CERN-EU (CERF) reference field facility. Various instruments were
      employed: conventional and extended-range rem counters including a novel
      instrument called LUPIN, a bubble detector using an active counting system (ABC
      1260) and two tissue-equivalent proportional counters (TEPCs). The results show
      that the extended range instruments agree well within their uncertainties and
      within 1sigma with the H*(10) FLUKA value. The conventional rem counters are in
      good agreement within their uncertainties and underestimate H*(10) as measured by
      the extended range instruments and as predicted by FLUKA. The TEPCs slightly
      overestimate the FLUKA value but they are anyhow consistent with it when taking
      the comparatively large total uncertainties into account, and indicate that the
      non-neutron part of the stray field accounts for ~30 % of the total H*(10). 

PMID- 24292485
TI  - A chemoproteomic platform to quantitatively map targets of lipid-derived
      electrophiles.
AB  - Cells produce electrophilic products with the potential to modify and affect the
      function of proteins. Chemoproteomic methods have provided a means to
      qualitatively inventory proteins targeted by endogenous electrophiles; however,
      ascertaining the potency and specificity of these reactions to identify the sites
      in the proteome that are most sensitive to electrophilic modification requires
      more quantitative methods. Here we describe a competitive activity-based
      profiling method for quantifying the reactivity of electrophilic compounds
      against >1,000 cysteines in parallel in the human proteome. Using this approach,
      we identified a select set of proteins that constitute 'hot spots' for
      modification by various lipid-derived electrophiles, including the oxidative
      stress product 4-hydroxy-2-nonenal (HNE). We show that one of these proteins, ZAK
      kinase, is labeled by HNE on a conserved, active site-proximal cysteine and that
      the resulting enzyme inhibition creates a negative feedback mechanism that can
      suppress the activation of JNK pathways normally induced by oxidative stress. 

PMID- 24292487
TI  - Measurement of potential alpha energy exposure and potential alpha energy
      concentration and estimating radiation dose of radon in Sari city in the north
      region of Iran.
AB  - In dwellings in Sari city in the northern region of Iran, the potential alpha
      energy exposure (PAEE) and potential alpha energy concentration (PAEC) have been
      measured and the radiation dose due to radon and its progenies has been
      estimated. In this study, the dosemeters DOSEman and SARAD GmbH (Germany), which
      are sensitive to alpha particles, were used. The population of the city of Sari
      is 495,369 people and the density of population is 116.5 people per km(2). A
      percentage of the total household population of Sari in areas of geographically
      different samples was selected. The PAEE, PAEC and radon concentration in four
      different seasons in a year in homes for sampling were measured. The mean PAEE
      due to indoor radon in homes of four cities in Sari city was estimated to be
      28.23 Bq m(-3) and the mean PAEC was estimated to be 27.11 Bq m(-3). Also the
      mean indoor radon level was found to be 29.95 Bq m(-3). The annual dose
      equivalent is ~0.0151 MUSv y(-1). Measurement results show that the average PAEE,
      PAEC and radon concentration are higher in winter than in other seasons. This
      difference could be due to stillness and lack of air movement indoors in winter.

PMID- 24292489
TI  - Tamponade dressings may be unnecessary after haemorrhoidectomy: a randomised
      controlled clinical trial.
AB  - PURPOSE: Bleeding after haemorrhoidectomy is common. Many surgical textbooks
      recommend insertion of an anal tampon in order to reduce postoperative bleeding.
      This practice, however, is bothersome and probably painful for patients. The
      effect of using a tamponade has not been validated in randomised controlled
      trials. METHODS: The study included 100 patients who were scheduled for Milligan
      Morgan haemorrhoidectomy. During surgery, patients were randomly assigned to
      receive or not to receive an anal tampon at the end of the procedure. Data on
      pain, complications and wound care were collected. The trial was registered
      (DRKS00003116) and all analyses were by intention-to-treat. RESULTS: There were
      48 patients in the group with tamponade, and 52 patients were left without
      tamponade. The trial's primary outcome and maximum pain intensity, averaged 6.1
      and 4.2 in the two groups (P = 0.001). In the group with tamponade, a
      complication was recorded in seven patients (15 %), which was similar to the
      group without tamponade (21 %). Severe anal bleeding occurred in two and five
      patients, respectively. Bandage changes were less necessary often in the group
      treated without tamponade (P = 0.013). Hospital stay was 4 days in both groups.
      CONCLUSIONS: Data indicate that insertion of an anal tampon after
      haemorrhoidectomy does not reduce postoperative bleeding but causes significantly
      more pain. After haemorrhoidectomy, anal tampons should not be used routinely but
      may be considered when specific indications justify its use.

PMID- 24292488
TI  - Risk of cancer and secondary proctectomy after colectomy and ileorectal
      anastomosis in familial adenomatous polyposis.
AB  - PURPOSE: The aim of our retrospective study was to review the outcome of patients
      undergoing colectomy with ileorectal anastomosis (IRA) due to familial
      adenomatous polyposis (FAP) in Finland during the last 50 years. METHODS: The
      cumulative risk of rectal cancer and the rate of anus preservation were analyzed.
      A total of 140 FAP patients with previous colectomy combined with ileorectal
      anastomosis were included. Kaplan-Meier analysis was performed to evaluate
      cumulative risks. RESULTS: Secondary proctectomy was performed for 39 (28 %) of
      140 patients. The cumulative risk of secondary proctectomy was 53 % at 30 years
      after colectomy with IRA. A total of 17 (44 %) secondary proctectomies were
      performed due to cancer or suspicion of cancer, and another 17 (44 %) secondary
      proctectomies were performed due to uncontrollable rectal polyposis. During our
      study, the anus preservation rate in secondary proctectomies was 49 %. The
      cumulative risk of rectal cancer was 24 % at 30 years after colectomy with IRA.
      Therefore, the cumulative rectal cancer mortality 30 years after colectomy with
      IRA was 9 %. CONCLUSIONS: Proctocolectomy and ileal pouch-anal anastomosis (IPAA)
      should be favored as a primary operation for patients not having technical or
      medical contraindications for it because colectomy with IRA carried a rectal
      cancer risk of 13 % with a mortality of 7 % during our study, and because IPAA is
      likely to succeed better at earlier phase of the disease. Patients with
      attenuated FAP had no rectal cancer in our study, and they may form a group where
      IRA should still be the first choice as an exception.

PMID- 24292490
TI  - Integrating various common indexes of bony alignment in femoral supracondyle.
AB  - OBJECTIVE: Indexes, which can optimally represent the bony alignment around the
      knee, are still controversial. Three common indexes, mechanical axis (MA),
      anatomic axis (AA), and anatomic lateral distal femoral angle (aLDFA), were
      integrated to simplify patient follow-up in the femoral supracondylar region.
      MATERIALS AND METHODS: Eighty consecutive adult patients (40 men, 40 women; age
      range 19-40 years) were studied using a full-length standing scanogram. Thirteen
      indexes, including MA, AA, and aLDFA, were measured and integrated. The
      relationships among these indexes were analyzed. RESULTS: The MA of the lower
      extremity passed with an average of 6.6 mm (9.2% of the tibial articular surface
      width) medial to the knee center. The supracondylar axis (SA) was an average of
      2.0 degrees  more valgus than the AA in the femoral supracondyle. An average 1.1
      degrees  deviation was noted in the AA, as measured by the femoral shaft axis or
      a line connecting the piriformis fossa to the knee center. CONCLUSION: The
      femoral MA may be more favorable than the MA of the lower extremity in order to
      represent an ideal weight-bearing line. The AA and aLDFA may be measurable via
      the SA in the anteroposterior view of the plain knee radiograph. Thus, patient
      follow-up becomes much more convenient.

PMID- 24292491
TI  - Three-dimensional fast imaging employing steady-state acquisition MRI and its
      diagnostic value for lumbar foraminal stenosis.
AB  - The aim of this study was to evaluate the usefulness of three-dimensional (3D)
      fast imaging employing steady-state acquisition (3D FIESTA) in the diagnosis of
      lumbar foraminal stenosis (LFS). Fifteen patients with LFS and 10 healthy
      volunteers were studied. All patients met the following criteria: (1) single L5
      radiculopathy without compressive lesion in the spinal canal, (2) pain
      reproduction during provocative radiculography, and (3) improvement of symptoms
      after surgery. We retrospectively compared the symptomatic nerve roots to the
      asymptomatic nerve roots on fast spin-echo (FSE) T1 sagittal, FSE T2 axial and
      reconstituted 3D FIESTA images. The kappa values for interobserver agreement in
      determining the presence of LFS were 0.525 for FSE T1 sagittal images, 0.735 for
      FSE T2 axial images, 0.750 for 3D FIESTA sagittal, 0.733 for axial images, and
      0.953 for coronal images. The sensitivities and specificities were 60 and 86 %
      for FSE T1 sagittal images, 27 and 91 % for FSE T2 axial images, 60 and 97 % for
      3D FIESTA sagittal images, 60 and 94 % for 3D FIESTA axial images, and 100 and 97
      % for 3D FIESTA coronal images, respectively. 3D FIESTA can provide more reliable
      and additional information for the running course of lumbar nerve root, compared
      with conventional magnetic resonance imaging. Particularly, use of 3D FIESTA
      coronal images enables accurate diagnosis for LFS. 

PMID- 24292492
TI  - Perceptual scaling of visual and inertial cues: effects of field of view, image
      size, depth cues, and degree of freedom.
AB  - In the field of motion-based simulation, it was found that a visual amplitude
      equal to the inertial amplitude does not always provide the best perceived match
      between visual and inertial motion. This result is thought to be caused by the
      "quality" of the motion cues delivered by the simulator motion and visual
      systems. This paper studies how different visual characteristics, like field of
      view (FoV) and size and depth cues, influence the scaling between visual and
      inertial motion in a simulation environment. Subjects were exposed to simulator
      visuals with different fields of view and different visual scenes and were asked
      to vary the visual amplitude until it matched the perceived inertial amplitude.
      This was done for motion profiles in surge, sway, and yaw. Results showed that
      the subjective visual amplitude was significantly affected by the FoV, visual
      scene, and degree-of-freedom. When the FoV and visual scene were closer to what
      one expects in the real world, the scaling between the visual and inertial cues
      was closer to one. For yaw motion, the subjective visual amplitudes were
      approximately the same as the real inertial amplitudes, whereas for sway and
      especially surge, the subjective visual amplitudes were higher than the inertial
      amplitudes. This study demonstrated that visual characteristics affect the
      scaling between visual and inertial motion which leads to the hypothesis that
      this scaling may be a good metric to quantify the effect of different visual
      properties in motion-based simulation. 

PMID- 24292493
TI  - Atypical monitoring and responsiveness to goal-directed gaze in autism spectrum
      disorder.
AB  - We hypothesized that difficulty in understanding the goals of others' actions in
      autism spectrum disorder (ASD) might be linked to a diminished attention and
      responsivity to relevant social cues. Using an eye-tracking paradigm, we
      investigated how 24 children with ASD and 24 matched children without ASD
      responded to the observation of uncompleted actions without a clear target
      (neutral condition) versus a condition in which the actor's gaze direction
      indicated the target of the actions (head-turning condition). Children without
      ASD significantly increased their attention to the actor's face and to the
      action's target in the head-turning condition compared to the neutral condition,
      while this was not the case in the ASD group. Overall, our findings suggest a
      diminished monitoring and responsivity to social cues signalling goal
      directedness, which might impact on the ability to understand other's action
      goals in young children with ASD. 

PMID- 24292494
TI  - Direction-dependent differences in temporal kinematics for vertical prehension
      movements.
AB  - In our daily lives, we can appropriately perform movements on the earth,
      suggesting that the central nervous system takes into account gravitational
      forces that act on our bodies during the movements. Recently, gravitational
      forces have been observed to generate the direction-dependent differences in the
      spatial properties of the kinematics of prehension movements. However, little is
      known about how gravitational forces affect the temporal properties of the
      kinematics of these movements. In this study, we tried to elucidate the
      gravitational effects on the temporal properties of the kinematics of movements
      by comparing upward (against gravity) and downward (with gravity) movements. As a
      result, we found the direction-dependent differences in temporal kinematics in
      both the reaching and grasping components of movements. For the reaching
      component, a shorter acceleration time was observed for the upward movements
      compared to the downward movements. For the grasping component, participants
      opened their hands earlier and faster for the upward movements than for the
      downward movements. These direction-dependent differences in the temporal
      kinematics suggested that the central nervous system takes into account and takes
      advantage of gravitational effects in the motor plans and controls of vertical
      prehension movements. 

PMID- 24292496
TI  - Acculturation stress and mental health among the marriage migrant women in Busan,
      South Korea.
AB  - Our study investigated mental health and associated factors, especially
      acculturation stress and coping resources, among "marriage migrant" women. Cross
      sectional data were collected for 501 marriage migrant women, about 10 % of those
      living in Busan, South Korea. Acculturation stress, coping resources,
      sociodemographic factors were examined using structured questionnaires, and the
      General Health Questionnaire-28 was administered as a measure of mental health.
      Many factors were related to mental health, especially marital satisfaction. Core
      cultural shock and self-rated economic status, interpersonal stress, and social
      support were also significantly related to mental health status. This study
      highlights the importance of marriage migrant women's mental health in South
      Korea. To improve their mental health, increased marital satisfaction, social
      support, resettlement funds, and/or educational programs that foster coping are
      needed. Additionally, we should encourage establishment of and participation in
      marriage migrant self-help groups, which can facilitate adaptation to marriage
      and to Korean culture.

PMID- 24292495
TI  - Finite element prediction of transchondral stress and strain in the human hip.
AB  - Cartilage fissures, surface fibrillation, and delamination represent early signs
      of hip osteoarthritis (OA). This damage may be caused by elevated first principal
      (most tensile) strain and maximum shear stress. The objectives of this study were
      to use a population of validated finite element (FE) models of normal human hips
      to evaluate the required mesh for converged predictions of cartilage tensile
      strain and shear stress, to assess the sensitivity to cartilage constitutive
      assumptions, and to determine the patterns of transchondral stress and strain
      that occur during activities of daily living. Five specimen-specific FE models
      were evaluated using three constitutive models for articular cartilage:
      quasilinear neo-Hookean, nonlinear Veronda Westmann, and tension-compression
      nonlinear ellipsoidal fiber distribution (EFD). Transchondral predictions of
      maximum shear stress and first principal strain were determined. Mesh convergence
      analysis demonstrated that five trilinear elements were adequate through the
      depth of the cartilage for precise predictions. The EFD model had the stiffest
      response with increasing strains, predicting the largest peak stresses and
      smallest peak strains. Conversely, the neo-Hookean model predicted the smallest
      peak stresses and largest peak strains. Models with neo-Hookean cartilage
      predicted smaller transchondral gradients of maximum shear stress than those with
      Veronda Westmann and EFD models. For FE models with EFD cartilage, the
      anterolateral region of the acetabulum had larger peak maximum shear stress and
      first principal strain than all other anatomical regions, consistent with
      observations of cartilage damage in disease. Results demonstrate that tension
      compression nonlinearity of a continuous fiber distribution exhibiting strain
      induced anisotropy incorporates important features that have large effects on
      predictions of transchondral stress and strain. This population of normal hips
      provides baseline data for future comparisons to pathomorphologic hips. This
      approach can be used to evaluate these and other mechanical variables in the
      human hip and their potential role in the pathogenesis of osteoarthritis (OA). 

PMID- 24292497
TI  - Assessing squalor in hoarding: the Home Environment Index.
AB  - The current study examined a new measure of squalor associated with hoarding, the
      Home Environment Index (HEI). Participants (N = 793) were recruited from a large
      database of individuals who sought information about hoarding following national
      media appearances and consented to an internet study. Participants completed
      measures of hoarding and related psychopathology, including the HEI. The HEI
      showed good internal consistency and construct validity and reflected a single
      factor of home squalor (15 items). The HEI correlated positively with measures of
      hoarding and mood psychopathology. Recommendations for future modifications and
      further study are provided.

PMID- 24292498
TI  - Morphological analysis of the glenoid version in the axial plane according to
      age.
AB  - PURPOSE: Total shoulder arthroplasty planning requires a preoperative assessment
      of the glenoid version. This study aimed to determine the morphologic profile of
      the glenoid cavity and our null hypothesis was that age may affect the spiraling
      aspect. METHOD: 114 CT arthrographies of patients from 15 to 78 years old were
      included. Four groups were defined according to age: 15-29, 30-44, 45-59 years
      old, and over 60. The version of the glenoid was measured in the axial plane
      according to the most common method: a line is drawn between the osseous anterior
      and posterior margins of the glenoid and the version corresponds to the angle
      between this line and the transverse axis of the glenoid. The transverse axis of
      the scapula is determined by a line drawn from the center of the glenoid fossa to
      the medial border of the scapula. The axial plane (perpendicular to the supero
      inferior axis of the glenoid cavity) was defined by multiplanar reconstruction.
      The measurements were performed at three regions of interest: the level of the
      coracoid process (region A), the level of the notch on the anterior border of the
      glenoid (region B), and the region of the greater antero-posterior diameter
      (region C). RESULTS: 96 % of the glenoid cavities included were retroverted. The
      mean version in region A was 11.9 degrees  (0-24.3, S-D 5.2), in region B 6.85
      degrees  (-5.2 to 12.1, S-D 4.13) and in region C 4.04 degrees  (-7.7 to 11.1, S
      D 4.04). The difference between the mean version of region A and region B was
      5.02 degrees  and the difference between the mean version of the region B and the
      mean version of the region C was 2.81 degrees . When considering the rate of
      change of the mean version between two adjacent regions, no difference was
      observed between the four groups of age. DISCUSSION: The analysis showed the
      importance of the axial reconstruction plan chosen to allow interpretable and
      reproducible measures. A decreasing version of the glenoid superior-to-inferior
      was observed, presenting a spiraling twist as described in previous studies. The
      profile of variation does not change in the four groups of patients included. The
      reconstruction of an articular surface as close to the anatomy as possible would
      also participate in establishing the muscular balance and the constraints on
      implants. Up to now, implants do not take into account this cranio-caudal
      twisting.

PMID- 24292499
TI  - Branching patterns and localization of the common fibular (peroneal) nerve: an
      anatomical basis for planning safe surgical approaches.
AB  - PURPOSE: Given the severity and incidence of injury to the common fibular
      (peroneal) nerve (CFN), there is a need to further clarify its anatomical
      location and branching patterns. This project attempts to consolidate current
      anatomical understanding of this nerve and provide physicians with reproducible
      measurements regarding the CFN and its branches. METHODS: Dissections were
      performed on 50 specimens (28 cadavers), both fresh and preserved. The CFN was
      dissected from its emergence from the fibular tunnel to its anterior tibial
      recurrent nerve (ATRN), superficial fibular nerve (SFN), and deep fibular nerve
      (DFN) branches. The CFN branching patterns were assessed and all variations were
      categorized into four types. RESULTS: Several significant relationships were
      identified between observable traits and key anatomical characteristics of the
      CFN. A significant correlation was found between fibular length and distance from
      the tip of the fibula to the DFN/ATRN branch, as well as between fibular length
      and distance from the tibial tuberosity to the SFN/DFN and DFN/ATRN branches. An
      association was identified between length of exposed sub-cutaneous CFN and
      height. Thickness of the biceps femoris tendon correlated significantly with BMI.
      CONCLUSIONS: These findings allow physicians to better assess a patient's
      individual CFN anatomy based on correlations with measureable physical traits and
      will contribute to anatomic education and successful completion of various
      surgical, anesthetic, and physical therapy procedures.

PMID- 24292500
TI  - Developmental variation of the SUUR protein binding correlates with gene
      regulation and specific chromatin types in D. melanogaster.
AB  - Eukaryotic genomes are organized in large chromatin domains that maintain proper
      gene activity in the cell. These domains may be permissive or repressive to the
      transcription of underlying genes. Based on its protein makeup, chromatin in
      Drosophila cell culture has been recently categorized into five color-coded
      states. Suppressor of Under-Replication (SUUR) protein was found to be the major
      component present in all three repressive chromatin states named BLACK, BLUE, and
      GREEN and to be depleted from the active YELLOW and RED chromatin types. Here, we
      addressed the question of developmental dynamics of SUUR binding as a marker of
      repressed chromatin types. We established genomewide SUUR binding profiles in
      larval salivary gland, brain, and embryos using DNA adenine methyltransferase
      identification (DamID) technique, performed their pairwise comparisons and
      comparisons with the published data from Drosophila Kc cells. SUUR binding
      pattern was found to vary between the samples. Increase in SUUR binding
      predominantly correlated with local gene repression suggesting heterochromatin
      formation. Reduction in SUUR binding often coincided with activation of tissue
      specific genes probably reflecting the transition to permissive chromatin state
      and increase in accessibility to specific transcription factors. SUUR binding
      plasticity accompanied by the regulation of the underlying genes was mainly
      observed in BLACK, BLUE, and RED chromatin types. Our results provide novel
      insight into the developmental dynamics of repressive chromatin and reveal a link
      to the chromatin-guided regulation of gene expression. 

PMID- 24292501
TI  - Bispecific Her2 * cotinine antibody in combination with cotinine-(histidine)2
      iodine for the pre-targeting of Her2-positive breast cancer xenografts.
AB  - PURPOSE: Cotinine has optimal characteristics as a hapten for pre-targeted
      radioimmunotherapy (PRIT). This study was performed to evaluate the applicability
      of cotinine/anti-cotinine antibody to PRIT. METHODS: We developed and prepared a
      tandem, single-chain, variable fragment Fc fusion protein [tandem single-chain
      variable fragment (scFv) Fc fusion protein] that is reactive to both human
      epidermal growth factor receptor 2 (Her2) and cotinine. Its simultaneous
      reactivity to Her2 and cotinine was tested in an enzyme-linked immunosorbent
      assay (ELISA) and two radioimmunoassays (RIA) employing Her2-coated RIA tubes and
      a Her2-overexpressing cell line. For in vivo imaging, mice bearing Her2-positive
      tumors were injected with a mixture of tandem scFv Fc fusion and (125)I-cotinine
      conjugated histidine dipeptide ((125)I-cotinine peptide). After a delay, (125)I
      cotinine peptide was injected again. RESULTS: ELISA and RIA results showed that
      tandem scFv Fc fusion protein successfully bound to both Her2 and cotinine. In
      single-photon emission computed tomography (SPECT), the complex of tandem scFv Fc
      fusion protein and (125)I-cotinine peptide was localized to Her2-positive tumor
      xenografts in mice 4 h after the first injection. Enhanced radioactivity at the
      site of the Her2-positive tumor lesion was monitored 1 h after the second
      injection. CONCLUSIONS: With these findings, we conclude that the tandem scFv Fc
      fusion protein and cotinine hapten system have the potential to be applied in
      PRIT.

PMID- 24292502
TI  - Detection of pelvic lymph node micrometastasis by real-time reverse transcriptase
      polymerase chain reaction in prostate cancer patients after hormonal therapy.
AB  - OBJECTIVE: To determine the feasibility of prostatic-specific antigen (PSA) mRNA
      and prostatic-specific membrane antigen (PSMA) mRNA measurement in detection of
      pelvic lymph node (PLN) micrometastasis for prostate cancer (PCa) after hormonal
      therapy (HT). METHODS: Fifty-four patients diagnosed as high risk localized PCa
      were given HT for 3 months before radical prostatectomy. Under bipedal
      lymphangiography, a needle was punctured into involved lymph nodes (LN) and
      aspirated lymphatic fluid was obtained preoperatively. The expression of PSA mRNA
      and PSMA mRNA in aspirated fluid was assessed by a fully quantitative real-time
      reverse transcriptase polymerase chain reaction (RT-PCR) and also in LN specimens
      from pelvic lymphadenectomy during prostatectomy. RESULTS: Median follow-up was
      36 months (range 18-58 months). Without histological evidence of PLN metastasis,
      twelve patients showed positive PSA and/or PSMA mRNA expressions and regarded as
      having micrometastases to PLNs. Biochemical recurrence (BCR) rate and interval
      between prostatectomy and BCR in patients with micrometastases (group B) were not
      significantly different to histologically proven PLN metastatic patients (group
      A) (58.3 vs. 83.3 %, P = 0.26; 10.9 vs. 9.2 months, P = 0.29, respectively), but
      significantly different to those with no PLN involvement (group C) (58.3 vs. 11.1
      %, P = 0.002; 10.9 vs. 21.3 months, P < 0.001, respectively). Kaplan-Meier
      analysis showed both groups A and B had significantly lower non-BCR rate than
      group C (P < 0.001, P < 0.001, respectively). CONCLUSIONS: For PCa patients
      receiving HT, measurement of PSA mRNA and PSMA mRNA in aspirated PLN fluid by
      real-time RT-PCR could effectively detect PLN micrometastases without surgical
      intervention.

PMID- 24292504
TI  - Charge transfer-assisted self-limited decyanation reaction of TCNQ-type electron
      acceptors on Cu(100).
AB  - TCNQ derivatives adsorbed on a metal surface undergo a self-limited decyanation
      reaction that only affects two out of the four cyano groups in the molecule.
      Combined Scanning Tunneling Microscopy/X-ray Photoelectron Spectroscopy
      experiments and Density Functional Theory calculations relate the self-limiting
      behavior to the transfer of electrons from the metal to the molecule. 

PMID- 24292503
TI  - Burden of disease in multiple sclerosis patients with spasticity in Germany:
      mobility improvement study (Move I).
AB  - OBJECTIVES: To describe the current management patterns of multiple sclerosis
      (MS) patients with spasticity in Germany and the impact of MS spasticity on
      quality of life (QoL) and associated costs. METHODS: Non-interventional,
      multicentre, cross-sectional and retrospective burden-of-disease study including
      414 MS patients with spasticity (age from 25 to 80 years) from 42 clinical
      practices across Germany. All patients were diagnosed with MS-related spasticity
      based on neurological examination at least 12 months before inclusion in the
      study. Three different forms were completed on different aspects of the disease:
      the patient questionnaire, the chart documentation form and the physician
      questionnaire. RESULTS: Mild, moderate and severe spasticity were found in 27.3,
      44.0 and 28.7 % of patients, respectively. Associated symptoms and QoL scores
      were worse in patients with higher degrees of spasticity. In particular, higher
      mean scores for sleep impairment (mild vs. severe, 2.1 vs. 4.3), mean spasm count
      (3/day vs. 10.1/day), mean WEIMuS fatigue score (15.8 vs. 19.8), increased
      walking time (9.6 vs. 20.2 s) and lower mean QoL scores (MSQoL-54 physical
      subscale, 54.9 vs. 39.5; EQ-5D, 0.60 vs. 0.30) were reported in patients with
      severe spasticity in comparison to patients with mild spasticity. Patient
      management mainly comprised physiotherapy (mild vs. severe, 65.5 vs. 85.7 %) and
      medication (84.2 vs. 64.8 %) with baclofen. The average cost for patients with
      mild spasticity was ?2,268/year, increasing to ?8,688/patient/year for patients
      with severe spasticity. The health insurance costs showed the same trend.
      CONCLUSIONS: MS patients with spasticity suffer a significant burden because of
      resulting disabilities and reduced QoL, especially in cases of severe spasticity.
      Moreover, spasticity causes high costs that increase with increasing severity.

PMID- 24292505
TI  - Extracellular NAD(+) inhibits human neutrophil apoptosis.
AB  - Regulation of neutrophil apoptosis plays a critical role in the inflammatory
      response. Inflammation has previously been shown to increase levels of
      extracellular beta-nicotinamide adenine dinucleotide (NAD(+)). The present study
      demonstrates that extracellular NAD(+) at concentrations found in the inflamed
      tissues profoundly delays spontaneous apoptosis of human neutrophils as was
      evidenced by inhibition of phosphatidylserine (PS) exposure, DNA fragmentation
      and caspase-3 activation. The effect was abrogated by NF157, an antagonist of
      P2Y11 receptor, and was pertussis toxin-insensitive. The NAD(+)-mediated delay of
      neutrophil apoptosis was reversed by 2',5'-dideoxyadenosine, an inhibitor of
      adenylyl cyclase, and Rp-8-Br-cAMPS, an inhibitor of type I cAMP-dependent
      protein kinase A (PKA). Blocking of NAD(+)-induced influx of extracellular Ca(2+)
      with EGTA did not abolish the pro-survival effect of NAD(+). Extracellular NAD(+)
      inhibited proteasome-dependent degradation of Mcl-1 upstream of caspase
      activation and, furthermore, suppressed Bax translocation to the mitochondria and
      attenuated both dissipation of mitochondrial transmembrane potential (DeltaPsim)
      and cytochrome c release from the mitochondria into the cytosol. Finally, we
      found that extracellular NAD(+) inhibited spontaneous activation of caspase-9,
      but not caspase-8, and the pro-survival effect of extracellular NAD(+) was
      abrogated by the inhibitor of caspase-9, but not by the inhibitor of caspase-8.
      Together, these results demonstrate that extracellular NAD(+) inhibits neutrophil
      apoptosis via P2Y11 receptor and cAMP/PKA pathway by regulating Mcl-1 level, Bax
      targeting to the mitochondria and mitochondrial apoptotic pathway. Thus,
      extracellular NAD(+) acts as a neutrophil survival factor that can contribute to
      prolonged neutrophil lifespan in inflammatory response. 

PMID- 24292507
TI  - Molecular assembly, interfacial rheology and foaming properties of oligofructose
      fatty acid esters.
AB  - Two major types of food-grade surfactants used to stabilize foams are proteins
      and low molecular weight (LMW) surfactants. Proteins lower the surface tension of
      interfaces and tend to unfold and stabilize the interface by the formation of a
      visco-elastic network, which leads to high surface moduli. In contrast, LMW
      surfactants lower the surface tension more than proteins, but do not form
      interfaces with a high modulus. Instead, they stabilize the interface through the
      Gibbs-Marangoni mechanism that relies on rapid diffusion of surfactants, when
      surface tension gradients develop as a result of deformations of the interface. A
      molecule than can lower the surface tension considerably, like a LMW surfactant,
      but also provide the interface with a high modulus, like a protein, would be an
      excellent foam stabilizer. In this article we will discuss molecules with those
      properties: oligofructose fatty acid esters, both in pure and mixed systems.
      First, we will address the synthesis and structural characterization of the
      esters. Next, we will address self-assembly and rheological properties of
      air/water interfaces stabilized by the esters. Subsequently, this paper will deal
      with mixed systems of mono-esters with either di-esters and lauric acid, or
      proteins. Then, the foaming functionality of the esters is discussed. 

PMID- 24292508
TI  - On the set of the numbers of conjugates of noncyclic proper subgroups of finite
      groups.
AB  - Let G be a finite group and N C (G) the set of the numbers of conjugates of
      noncyclic proper subgroups of G. We prove that (1) if |N C G)| <= 2, then G is
      solvable, and (2) G is a nonsolvable group with |N C (G)| = 3 if and only if
      G?PSL(2,5) or PSL(2,13) or SL(2,5) or SL(2,13).

PMID- 24292510
TI  - Facile preparation of hierarchically porous polymer microspheres for
      superhydrophobic coating.
AB  - A facile method, i.e., nonsolvent assisted electrospraying, is proposed to
      fabricate hierarchically porous microspheres. The pore size on the microsphere
      surface ranges from a few tens to several hundred nanometers. Thermally and
      nonsolvent induced phase separation as well as breath figure is responsible for
      the formation of the hierarchical structures with different nano-sized pores. The
      nonsolvent could not only induce phase separation, but also stabilize the
      interface between the droplet and air, which can prevent the droplet from strong
      deformation, and is therefore beneficial to the formation of regular and uniform
      microspheres. On the other hand, solvent evaporation, polymer diffusion and
      Coulomb fission during electrospraying influence the morphology of finally
      obtained products. In this paper, the influence of polymer concentration, the
      weight ratio between nonsolvent and polymer and the flowing rate on the
      morphology of the porous microsphere is carefully studied. The hierarchically
      porous microsphere significantly increases the surface roughness and thus the
      hydrophobicity, and the contact angle can reach as high as 152.2 +/- 1.2 degrees
      . This nonsolvent assisted electrospraying opens a new way to fabricate
      superhydrophobic coating materials. 

PMID- 24292509
TI  - Sulfolobus tokodaii ST2133 is characterized as a thioredoxin reductase-like
      ferredoxin:NADP+ oxidoreductase.
AB  - The putative gene (st2133) for ferredoxin:NADP(+) oxidoreductase (FNR) from
      Sulfolobus tokodaii, a thermoacidophilic crenarchaeon, was heterologously
      expressed. About 90% of the purified product was a homodimer containing 0.46 mol
      FAD/mol subunit, and showing NADPH:DCPIP oxidoreductase activity, V max being
      1.38 and 21.8 U/mg (70  degrees C) in the absence and presence of 1 mM FMN. NADPH
      was a much better electron donor than NADH with various electron acceptors, such
      as oxygen, hydrogen peroxide, DCPIP, cytochrome c, and dithiobisnitrobenzoate.
      Most of the reactions were activated by 15- to 140-fold on addition of FMN, while
      FAD was 5-10 times less effective. Ferredoxin (Fd) from S. tokodaii served as an
      electron carrier in both Fd-dependent NADPH formation and NADPH-dependent Fd
      reduction. ST2133 belongs to the thioredoxin reductase-like protein family, which
      is slightly distantly related to FNR family proteins from bacteria, plants and
      man. This is the first report on FNR from a crenarchaeon, providing a clue to the
      recycling of Fd during archaeal metabolism.

PMID- 24292511
TI  - Synthesis of hierarchically structured ZnO nanomaterials via a supercritical
      assisted solvothermal process.
AB  - Hierarchically structured ZnO nanomaterials with flower-sheet-particle
      morphologies were synthesized via a supercritical assisted solvothermal process
      free from any other auxiliary chemicals. 

PMID- 24292512
TI  - Genetic diversity and linkage disequilibrium analysis in elite sugar beet
      breeding lines and wild beet accessions.
AB  - Linkage disequilibrium decay in sugar beet is strongly affected by the breeding
      history, and varies extensively between and along chromosomes, allowing
      identification of known and unknown signatures of selection. Genetic diversity
      and linkage disequilibrium (LD) patterns were investigated in 233 elite sugar
      beet breeding lines and 91 wild beet accessions, using 454 single nucleotide
      polymorphisms (SNPs) and 418 SNPs, respectively. Principal coordinate analysis
      suggested the existence of three groups of germplasm, corresponding to the wild
      beets, the seed parent and the pollen parent breeding pool. LD was investigated
      in each of these groups, with and without correction for genetic relatedness.
      Without correction for genetic relatedness, in the pollen as well as the seed
      parent pool, LD persisted beyond 50 centiMorgan (cM) on four (2, 3, 4 and 5) and
      three chromosomes (2, 4 and 6), respectively; after correction for genetic
      relatedness, LD decayed after <6 cM on all chromosomes in both pools. In the wild
      beet accessions, there was a strong LD decay: on average LD disappeared after 1
      cM when LD was calculated with a correction for genetic relatedness. Persistence
      of LD was not only observed between distant SNPs on the same chromosome, but also
      between SNPs on different chromosomes. Regions on chromosomes 3 and 4 that harbor
      disease resistance and monogermy loci showed strong genetic differentiation
      between the pollen and seed parent pools. Other regions, on chromosomes 8 and 9,
      for which no a priori information was available with respect to their
      contribution to the phenotype, still contributed to clustering of lines in the
      elite breeding material.

PMID- 24292513
TI  - Hierarchical assembly of metal nanoparticles, quantum dots and organic dyes using
      DNA origami scaffolds.
AB  - The self-assembly of nanoscale elements into three-dimensional structures with
      precise shapes and sizes is important in fields such as nanophotonics,
      metamaterials and biotechnology. Short molecular linkers have previously been
      used to create assemblies of nanoparticles, but the approach is limited to small
      interparticle distances, typically less than 10 nm. Alternatively, DNA origami
      can precisely organize nanoscale objects over much larger length scales. Here we
      show that rigid DNA origami scaffolds can be used to assemble metal
      nanoparticles, quantum dots and organic dyes into hierarchical nanoclusters that
      have a planet-satellite-type structure. The nanoclusters have a tunable
      stoichiometry, defined distances of 5-200 nm between components, and controllable
      overall sizes of up to 500 nm. We also show that the nanoscale components can be
      positioned along the radial DNA spacers of the nanostructures, which allows short
      and long-range interactions between nanoparticles and dyes to be studied in
      solution. The approach could, in the future, be used to construct efficient
      energy funnels, complex plasmonic architectures, and porous, nanoengineered
      scaffolds for catalysis. 

PMID- 24292514
TI  - Nanoparticle-detained toxins for safe and effective vaccination.
AB  - Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely
      used to promote antitoxin immunity for the treatment and prevention of bacterial
      infections. Following chemical or heat denaturation, inactivated toxins can be
      administered to mount toxin-specific immune responses. However, retaining
      faithful antigenic presentation while removing toxin virulence remains a major
      challenge and presents a trade-off between efficacy and safety in toxoid
      development. Here, we show a nanoparticle-based toxin-detainment strategy that
      safely delivers non-disrupted pore-forming toxins for immune processing. Using
      erythrocyte membrane-coated nanoparticles and staphylococcal alpha-haemolysin, we
      demonstrate effective virulence neutralization via spontaneous particle
      entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated
      with the nanoparticle-detained toxin showed superior protective immunity against
      toxin-mediated adverse effects. We find that the non-disruptive detoxification
      approach benefited the immunogenicity and efficacy of toxoid vaccines. We
      anticipate that this study will open new possibilities in the preparation of
      antitoxin vaccines against the many virulence factors that threaten public
      health.

PMID- 24292515
TI  - Three-question dementia screening. Development of the Salzburg Dementia Test
      Prediction (SDTP).
AB  - BACKGROUND: To date, short dementia screenings are often limited by poor
      specificity or still take too much time with respect to the restricted resources
      of primary care physicians and the increasing number of dementia disorders. As a
      new instrument, the three-question dementia screening (SDTP, Salzburg Dementia
      Test Prediction) should be compared with the eight-item screening of Chen et al.
      and the CERAD battery (Consortium to Establish a Registry for Alzheimer's
      Disease), focusing on specificity and economy of time. MATERIALS AND METHODS: We
      tested 404 patients (243 women). The mean age of the subjects was 80.1 years (SD
      = 6.8) for men and 83.2 years (SD = 6.0) for women. The mean Mini-Mental State
      Examination (MMSE) score was 21.9 (SD =  5.8) for men and 21.1 (SD =  6.3) for
      women. Artificial neural networks (ANNs) were used to find a mathematical model
      that allows the total MMSE to be predicted with only three questions of the MMSE.
      This is achieved by multiplying the outcome of the three best predictor questions
      with a weighting coefficient, which was delineated by using ANNs. RESULTS: The
      Salzburg Dementia Test Prediction (SDTP) had a sensitivity of 94% (95% CI: 87
      97%) for screening of possible dementia, when the MMSE (MMSE < 25/30) was used as
      the reference test method and 96% when the CERAD was used. The specificity was
      68% (95% CI: 57-77%) if the MMSE was used and 70% if the whole test battery
      (CERAD) was used, which is as sensitive as and more specific than the eight-item
      screening. CONCLUSION: The SDTP is a time-saving instrument for screening of
      dementia, which is as sensitive as and more specific than the eight-item
      screening of Chen et al. and provides a prediction of the MMSE with high
      accuracy.

PMID- 24292516
TI  - [Measuring gait velocity in the elderly with a gait analysis system and a 10
      meter walk test. A comparison].
AB  - BACKGROUND: Gait disorders are common in the elderly, compromising quality of
      life and increasing the risk for falls. Mobility and fall risk assessment usually
      includes measurement of gait velocity. Computerized gait analyses are able to
      measure additional gait parameters. MATERIALS AND METHODS: This study addressed
      the question whether elderly patients (n=66) change their self-selected gait
      speed when walking on a computerized platform compared to a 10-m walk test. A
      second aim was to compare gait velocity, gait parameters, and clinical
      measurements (TUG, POMA) in subgroups of patients with a history of a fall (n=27)
      vs. without a history of a fall (n=39). RESULTS: Our results demonstrate that
      gait velocity was significantly reduced in the subgroup of fallers, but not in
      the group of nonfallers. Moreover, other gait parameters and the clinical tests
      differed significantly between fallers and nonfallers. DISCUSSION: A possible
      explanation could be the visual requirements of the test environment, which may
      influence the walking speed in terms of a dual-task paradigm in those
      participants with mobility problems.

PMID- 24292517
TI  - Identifying axial and cognitive correlates in patients with Parkinson's disease
      motor subtype using the instrumented Timed Up and Go.
AB  - Parkinson's disease (PD) is clinically highly heterogeneous, often divided into
      tremor dominant (TD) and postural instability gait difficulty (PIGD). To better
      understand these subtypes and to help stratify patients, we applied an objective
      marker, i.e., an instrumented version of the traditional "Timed Up and Go" test
      (iTUG). It is not known whether the iTUG is sensitive to PD motor phenotypes or
      what are its behavioral and cognitive correlates. Subjects performed the iTUG
      wearing a body-fixed sensor. Subcomponents were studied including walking,
      transitions and turning. Gait, balance and cognitive function and the
      associations between iTUG, behavioral and cognitive domains were assessed. We
      also compared two representative subtypes, with minimal symptom overlap, referred
      to here as predominant PIGD (p-PIGD) and predominant TD (p-TD). One hundred and
      six patients with PD performed the iTUG. Significant correlations were found
      between iTUG measures and the PIGD score, but not with TD score. Thirty p-PIGD
      and 31 p-TD patients were identified. Both groups were similar with respect to
      age and disease duration (p > 0.75). The p-PIGD patients took significantly
      longer to complete the iTUG (p = 0.026), used more steps (p = 0.031), albeit with
      similar step duration (p = 0.936). In the sit-to-stand transition, the p-PIGD
      patients exhibited lower anterior-posterior jerk (p = 0.04) and lower pitch range
      (p = 0.012). During the turn, the p-PIGD patients had a lower yaw amplitude (p <
      0.038). Cognitive domains were correlated with iTUG measures in the p-PIGD
      patients, but not in the p-TD. These findings demonstrate that a single sensor
      can identify axial and cognitive correlates using subcomponents of the iTUG and
      reveals subtle alterations between the PD motor subtypes.

PMID- 24292518
TI  - Effects of strobe light stimulation on postnatal developing rat retina.
AB  - The nature and intensity of visual stimuli have changed in recent years because
      of television and other dynamic light sources. Although light stimuli accompanied
      by contrast and strength changes are thought to have an influence on visual
      system development, little information is available on the effects of dynamic
      light stimuli such as a strobe light on visual system development. Thus, this
      study was designed to evaluate changes caused by dynamic light stimuli during
      retinal development. This study used 80 Sprague-Dawley rats. From eye opening
      (postnatal day 14), half of the rats were maintained on a daily 12-h light/dark
      cycle (control group) and the remaining animals were raised under a 12-h strobe
      light (2 Hz)/dark cycle (strobe light-reared group). Morphological analyses and
      electroretinogram (ERG) were performed at postnatal weeks 3, 4, 6, 8, and 10.
      Among retinal neurons, tyrosine hydroxylase-immunoreactive (TH-IR, dopaminergic
      amacrine cells) cells showed marked plastic changes, such as variations in
      numbers and soma sizes. In whole-mount preparations at 6, 8, and 10 weeks, type I
      TH-IR cells showed a decreased number and larger somata, while type II TH-IR
      cells showed an increased number in strobe-reared animals. Functional assessment
      by scotopic ERG showed that a-wave and b-wave amplitudes increased at 6 and 8
      weeks in strobe-reared animals. These results show that exposure to a strobe
      light during development causes changes in TH-IR cell number and morphology,
      leading to a disturbance in normal visual functions.

PMID- 24292519
TI  - Influence of two different doses of antithymocyte globulin in patients with
      standard-risk disease following haploidentical transplantation: a randomized
      trial.
AB  - To evaluate the effect of the different doses of antithymocyte globulin (ATG) on
      the incidence of acute GVHD among patients receiving hematopoietic SCT without ex
      vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk
      hematological malignancy were randomized in this study. One hundred and twelve
      patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg
      ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC
      11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group
      (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%,
      CI, 0.7-8.3%, P=0.005, 95% CI for the difference, -19.4% to -3.8%). EBV
      reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%)
      than in the ATG-6 group (9.6% (4.0-15.2%), P=0.001). The 1-year disease-free
      survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group
      and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG
      applied in haploidentical transplantation decreased the risk of EBV reactivation
      compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for
      severe acute GVHD. 

PMID- 24292520
TI  - Allogeneic hematopoietic cell transplantation for myelofibrosis in patients
      pretreated with the JAK1 and JAK2 inhibitor ruxolitinib.
AB  - The Janus-activated kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is effective
      in decreasing symptomatic splenomegaly and myelofibrosis (MF)-related symptoms.
      However, allogeneic hematopoietic cell transplantation (HCT) remains the only
      curative option. We evaluated the impact of ruxolitinib on the outcome after HCT.
      A cohort of 14 patients (median age 58 years) received a subsequent graft from
      related (n=3) and unrelated (n=11) donors after a median exposure of 6.5 months
      to ruxolitinib. At HCT, MF risk for survival according to the International
      Prognostic Scoring System was intermediate-2 or high risk in 86% of patients.
      Under ruxolitinib, MF-related symptoms were ameliorated in 10 (71.4%) patients
      and the palpable spleen reduced by a median of 41% in 7 (64%) of 11 patients with
      splenomegaly. Engraftment occurred in 13 (93%) patients. Acute GvHD grade-III
      occurred in 2 (14%) patients. Median follow-up was 9 months. Survival, EFS and
      treatment-related mortality were 78.6, 64 and 7%, respectively. Through the anti
      JAK-mediated reduction in both cytokines and splenomegaly as well as improvement
      in performance status, ruxolitinib might improve outcome after allogeneic HCT in
      patients with MF. The downregulation of inflammatory cytokines might have a
      beneficial impact on graft failure and acute GvHD. 

PMID- 24292521
TI  - EBV-associated post-transplant lymphoproliferative disorder after umbilical cord
      blood transplantation in adults with hematological diseases.
AB  - We analyzed the incidence, clinicopathological features, risk factors and
      prognosis of patients with EBV-associated post-transplant lymphoproliferative
      disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation
      (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a
      median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of
      EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal
      involvement. Most frequently affected sites were the liver, spleen, central
      nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients,
      respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7
      diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic
      lymphomas). We confirmed donor origin and EBV infection in all histological
      samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23
      days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and
      2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning
      (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion,
      adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The
      prognosis was poor despite routine viral monitoring and early intervention. An
      increased risk of EBV-PTLD was noted among recipients of RIC regimens. 

PMID- 24292523
TI  - Suicidal behaviors and the use of mental health services among active duty Army
      soldiers.
AB  - OBJECTIVE: U.S. Army personnel experience a significant mental health burden,
      particularly during times of war and multiple deployments. This study identified
      rates of suicidality (seriously considering or attempting suicide) and types of
      mental health services used in the past 12 months by active duty Army soldiers.
      METHODS: This study used the 2008 Department of Defense Survey of Health Related
      Behaviors Among Active Duty Military Personnel, which sampled 10,400 Army
      soldiers from a total population of 508,088 soldiers. Mental health service
      utilization included receiving counseling or therapy from a general medical
      doctor, receiving counseling or therapy from a mental health professional, and
      being prescribed medications for depression, anxiety, or sleep. Suicidality was
      assessed via self-report questions. RESULTS: Thirteen percent had seriously
      considered or attempted suicide at some point in their lives, 7% since joining
      the military. One percent who reported suicidality since joining the Army
      reported having considered or attempted suicide in the past year. After the
      analyses adjusted for sociodemographic factors, soldiers who seriously considered
      or attempted suicide since joining the military versus those who did not were
      1.71 times more likely to have used a mental health service, 2.33 times more
      likely to have used two or more types of services, 1.82 times more likely to have
      seen a mental health specialist, and 1.67 times more likely to have received
      medication in the past year. CONCLUSIONS: Understanding the relationship between
      suicidal thoughts and behaviors and the specific levels and types of mental
      health services received in this military population is important for health care
      provision and planning.

PMID- 24292524
TI  - [Destruction of the articular cartilage in osteoarthritis].
AB  - Osteoarthritis (OA) is the most common joint disease characterized by destruction
      of articular cartilage induced primarily by mechanical stresses to joints.
      Destruction of the articular cartilage in OA is caused by combination of
      increased degradation of ECM (extracellular matrix) , decreased production of ECM
      and chondrocyte death. Members of the MMP (matrix metalloproteinase) and ADAMTS
      (a disintegrin and metalloproteinase with thrombospondin motifs) gene families
      are considered to play a key role in the degradation of cartilage. 

PMID- 24292525
TI  - [Cartilage repair and regenerative medicine ; past, present, and future].
AB  - Since the days of ancient Greece, it has been known that articular cartilage has
      poor potential to repair. In April, 2013, autologous chondrocyte implantation
      (ACI) was approved by the Japanese ministry of Health, Labour and Welfare, as the
      first orthopedic cell therapy in Japan. Half a century has passed since
      Chesterman's report on rabbit allogeneic chondrocyte implantation, and
      approximately 20 years since the first human ACI report by Brittberg. In Japan,
      24 years has passed since Wakitani's allogeneic chondrocyte implantation, and
      over 10 years since the human ACI report by Ochi. A long-term follow-up clinical
      trial with the high statistical power is needed to verify the safety and efficacy
      of new cartilage joint therapy. Moreover, we need the infrastructure, including
      drug and/or device regulation and timely approved by the government, to apply new
      therapies in similar time frames to other developed nations.

PMID- 24292522
TI  - Outcomes of adults with active or progressive hematological malignancies at the
      time of allo-SCT: a survey from the Societe Francaise de Greffe de Moelle et de
      Therapie Cellulaire (SFGM-TC).
AB  - Previous data suggested that allo-SCT might be an effective therapy in the
      setting of chemo-refractory/relapsed diseases because of the potent long-term
      immune-mediated tumor control. This retrospective study aimed to analyze the
      outcome of adult patients who received allo-SCT in a chemo-refractory/relapsed
      status. The series included 840 patients with active or progressive disease at
      the time of transplant. Median age was 50 years. With a median follow-up of 40
      months, 3-year OS, disease-free survival (DFS), and non-relapse mortality rates
      were 29+/-2, 23+/-2, and 30+/-2%, respectively. At the last follow-up, 252
      patients (30%) were still alive (of whom 201 were in CR (24%). In a Cox
      multivariate analysis, the use of a reduced-intensity conditioning (RIC) before
      allo-SCT and use of an HLA-identical sibling donor remained independently
      associated with a better OS (hazard ratio (HR)=0.82; 95% confidence interval
      (CI), 0.69-0.98, P=0.03; and HR=0.79; 95% CI, 0.66-0.93, P=0.006, respectively).
      Also, a diagnosis of myelodysplastic syndrome/myeloproliferative disorder,
      Hodgkin lymphoma and non-Hodgkin lymphoma compared with acute leukemia had a
      favorable impact on OS (HR=0.55; 95% CI, 0.45-0.68, P<0.0001; HR=0.49; 95% CI,
      0.31-0.75, P=0.001; and HR=0.47; 95% CI, 0.35-0.63, P<0.0001, respectively). In
      conclusion, this study suggests that allo-SCT may be of benefit in some subgroups
      of patients with active or progressive hematological malignancies at the time of
      allo-SCT. 

PMID- 24292526
TI  - [Identification of osteogenic signal and the development of artificial bones].
AB  - Mammalian skeletons are formed through two distinct processes, intramembranous
      ossification and endochondral ossification. During the endochondral ossification,
      indian hedgehog (Ihh) /parathyroid hormone-related protein (PTHrP) negative
      feedback loop regulates the distance between epiphysis and the layer of
      hypertrophic chondrocytes. Ihh also stimulates bone formation. Based on such
      knowledge, bioactive molecule-loaded artificial bones are expected to achieve
      efficient bone regeneration without cell transplantation. 

PMID- 24292527
TI  - [Development of meniscus biomaterial].
AB  - Meniscus is one of the most important tissues in knee joint from the
      biomechanical point of view. Meniscus injury is well known to cause
      osteoarthritis. At moment, there is a limitation of operative repair procedure
      especially for the meniscus injury with defect. We have been investigating the
      development of meniscus biomaterials. Meniscus substitute made of atelo-collagen
      was proved to be one of the candidates of meniscus biomaterial by our experiments
      using human cell culture, three-dimensional cultured tissue, and animal study. 

PMID- 24292528
TI  - [Articular cartilage regenerative therapy with synovial mesenchymal stem cells in
      a pig model].
AB  - Current therapies for cartilage injury remain some issues such as the quality of
      regenerated cartilage and its invasiveness. We have been trying to develop a low
      invasive treatment for cartilage regeneration with synovial mesenchymal stem
      cells (MSCs) . Here we introduce our preclinical study with miniature pigs whose
      knee joints are similar to those of humans in terms of size and cartilage
      metabolism. Cartilage defect was created at the weight bearing area of both
      porcine knee joints. Synovial MSCs were transplanted by delivering a synovial MSC
      suspension onto the cartilage defect of the one side and the knee was kept
      immobilized for 10 minutes. Sequential arthroscopic and histological observations
      showed the contribution of synovial MSCs after transplantation, and a better
      hyaline cartilaginous-tissue regeneration in the MSC-treated knees than in the
      non-treated control knees at 12 weeks. Based on this and other preclinical
      studies, we have started a clinical study for cartilage regeneration with
      autologous synovial MSCs. 

PMID- 24292529
TI  - [Articular cartilage therapy using cell sheet].
AB  - We previously reported achieving robust tissue repair in rabbits when covering
      only the surface layer of partial-thickness defects with layered chondrocyte
      sheets prepared in a temperature-responsive culture dish, and also reported
      excellent Safranin O staining and integration with surrounding tissue in a mini
      pig model of full-thickness cartilaginous defects in the knee joint. Thus we
      discovered that the layered chondrocyte sheets have therapeutic effects on the
      two types of cartilage damage which often exist in the joints of osteoarthritis
      patients. We have confirmed the safety of human chondrocyte sheets, and have
      submitted a report to the Ministry of Health, Labour, and Welfare in Japan. In
      2011, the Ministry gave us approval to perform a clinical study of joint repair
      using cell sheets. We have just started implanting cell sheets in patients at
      Tokai University Hospital. 

PMID- 24292530
TI  - [Endoplasmic reticulum stress response involved in osteogenesis and
      chondrogenesis].
AB  - The endoplasmic reticulum (ER) is a central cellular organelle responsible for
      the synthesis, folding and posttranslational modifications of proteins destined
      for the secretory pathway. Various pathophysiological conditions, such as ER
      calcium depletion, oxidative stress, hypoglycemia, expression of mutated proteins
      and hypoxia, interfere with the correct folding of proteins and these misfolded
      or unfolded proteins accumulate in the ER lumen. These conditions, which are
      collectively termed ER stress, have the potential to induce cellular damage.
      Recently, the ER stress has been demonstrated to be associated with bone and
      cartilage diseases. Further, it has been known that the ER stress and its stress
      response also play important roles in osteogenesis and chondrogenesis. 

PMID- 24292531
TI  - [Intravital optical imaging of bone and cartilage tissues].
AB  - Intravital optical imaging technique is a promising method that allows us to
      investigate complex vital phenomena in vivo . In particular, discovery and
      development of unique fluorescent proteins and smart fluorescent dyes in
      conjunction with appropriate equipment such as two-photon microscopy and image
      processing software allow visualization of the behavior and function of bone and
      cartilage-related cells as well as the microenvironment of the cells in bone and
      cartilage in living animals. Here we show recent technological development and
      issues of the intravital optical imaging and the application of the fluorescent
      imaging approaches to bone and cartilage biology.

PMID- 24292532
TI  - [Transcriptional regulation of chondrogenesis and articular cartilage
      destruction].
AB  - In 20th century, cartilage researches were performed by in vitro culture system,
      and current trend of mouse genetic approaches makes a good progress in the
      studies of molecular mechanisms underlying chondrogenesis. Sox family and Runt
      family transcription factors play central roles in chondrogenesis and
      pathogenesis of osteoarthritis. In this review, we would like to introduce recent
      progress in understanding of molecular regulation of transcription factors in
      chondrogenesis and articular cartilage destruction. 

PMID- 24292533
TI  - [Fetal therapy of skeletal dysplasias].
AB  - Three types of fetal therapy of skeletal dysplasias, as enzyme replacement, in
      utero stem cell transplantation, and gene therapy, are reviewed. Clinical trial
      of recombinant ALP for infantile hypophosphatasia has already started in Japan.
      In future, such enzyme replacement therapy is expected to be adapted to fetus.
      There are several reports of mesenchymal stem cell transplantation for
      osteogenesis imperfecta fetus. These case reports have showed that stem cell
      transplantation is safe and to some extent works in patients. No clinical trial
      for gene therapy has been reported. Recently, the study of gene therapy of using
      HPP fetal mouse showed an excellent therapeutic effect. Fetal therapy of skeletal
      dysplasias is still the stage of research because of the safety and the ethical
      issues. However, in order to treat severe cases of skeletal dysplasias which
      abnormal development has been already completed at birth, fetal therapy at an
      early stage would be demanded. 

PMID- 24292534
TI  - [Clinical condition and therapy of bone diseases].
AB  - Skeletal dysplasia is the term which represents disorders including growth and
      differentiation of bone, cartilage and ligament. A lot of diseases are included,
      and new disorders have been added. However, the therapy of most bone diseases is
      less well-established. Achondroplasia, hypochondroplasia, and osteogenesis
      imperfecta are most frequent bone diseases. There is no curative treatment for
      these diseases, however, supportive therapies are available ; for example, growth
      hormone therapy for achondroplasia and hypochondroplasia, and bisphosphonate
      therapy for osteogenesis imperfecta. In addition, enzyme replacement therapy for
      hypophosphatasia is now on clinical trial. 

PMID- 24292535
TI  - Self-powered visual ultraviolet photodetector with Prussian blue electrochromic
      display.
AB  - A novel self-powered ultraviolet (UV) photodetector was successfully constructed
      through combining Pt-modified TiO2 nanotubes and Prussian blue (PB)-modified ITO,
      in which the existence of UV could be judged easily by naked eye with the aid of
      PB for electrochromic display. More importantly, it could also self-recover
      without UV light illumination. 

PMID- 24292536
TI  - Ionomycin inhibits Jurkat T cell behaviors in the presence of phorbol-12,13
      dibutyrate.
AB  - Ionomycin in conjunction with phorbol-12,13-dibutyrate (PDBu) is conventionally
      used as a stimulator to activate cells, especially original T cells. But we
      accidently found it had an entirely opposite action on malignant tumor cells
      derived from T cells. Thus, influence of ionomycin on human leukemia Jurkat T
      cell behaviors and its preliminary mechanistic process were explored in the
      presence of PDBu. Ionomycin could remarkably inhibit colony formation of the
      cells, and inhibitory rate of the cell proliferation was increased with ionomycin
      treatment in a dose- or time-related relationship, following the reduction of
      ERK1/2 and phosphorylated-ERK1/2 levels. However, a high dose of ionomycin might
      moderately repress mid-stage activation of the cells. It also blocked the cell
      entry at S-phase and G2/M-phase with the attenuation of transforming growth
      factor-beta (TGF-beta) level in the cells, and promoted the cell apoptosis
      following the augment of caspase-3 and cleaved caspase-3 in the cells. The
      dramatic elevation of [Ca2(+)]i and intracellular pH (pHi) was simultaneously
      followed by the above alteration of the cell behaviors. These results indicate
      that ionomycin may strongly inhibit human acute T lymphocyte leukemia progress in
      the presence of PDBu through the inhibition of ERK1/2 signaling, the activation
      of caspase-3 and the attenuation of TGF-beta mediated by the [Ca2(+)]i and pHi
      enhancement, providing a novel insight into function and potential application of
      both ionomycin and PDBu. 

PMID- 24292537
TI  - Diagnosis of brainstem involvement in NK/T cell lymphoma.

PMID- 24292538
TI  - Hyperammonemic encephalopathy in multiple myeloma.

PMID- 24292539
TI  - EUTOS score predicts early optimal response to imatinib according to the revised
      2013 ELN recommendations.

PMID- 24292540
TI  - Novel enzyme-linked immunosorbent assay for bivalent ZnT8 autoantibodies.
AB  - Autoantibodies to zinc transporter 8 (ZnT8A) are a powerful diagnostic or
      predictive marker in type 1 diabetes. However, the widely used current ZnT8A
      radioligand binding assay (RBA) has proved to be difficult for many laboratories
      to implement. The aim of this study was the development and characterization of
      the performance of a novel fluid-phase ZnT8A enzyme-linked immunosorbent assay
      (ELISA) in relation to standard RBA in type 1 diabetes. Sera from 114 patients
      with type 1 diabetes and 140 blinded Islet Autoantibody Standardization Program
      (IASP2012) samples were studied. The sensitivity of ELISA-ZnT8A is equivalent to
      or slightly higher than that of conventional RBA with similar specificity.
      Furthermore, the median SD score using this ELISA was significantly higher than
      that obtained with RBA (P < 0.0001). Multiple logistic regression analysis
      revealed that ELISA-ZnT8A positivity was associated with younger age of onset
      (<=20 years; OR 15.91, P = 0.0002), acute-onset form of type 1 diabetes (OR 3.38,
      P = 0.019), and the presence of IA-2 autoantibodies (OR 3.75, P = 0.014).
      Furthermore, the levels of ELISA-ZnT8A were associated with the reactivity to
      ZnT8-325Arg, but not ZnT8-325Trp. We conclude that this nonradioactive bivalent
      ZnT8A assay has high performance and should facilitate large-scale autoantibody
      screening. Moreover, these results suggest that the humoral autoimmunity against
      ZnT8 is related to a high risk of faster development of type 1 diabetes and the
      ZnT8A levels are associated with the known aa325 variants. 

PMID- 24292541
TI  - Determination of the susceptibility of unengorged larvae and engorged females of
      Rhipicephalus microplus (Acari: Ixodidae) to different methods of dissolving
      thymol.
AB  - The present study evaluated efficacy of thymol against engorged females and
      unengorged larvae of Rhipicephalus microplus when diluted in 1 % dimethyl
      sulfoxide (DMSO) (formulation 1) and diluted in hydro-ethanol solutions of 50 %
      (formulation 2), 40 % (formulation 3), and 30 % (formulation 4). The immersion
      test was used on the engorged females for all dilution methods, while the larval
      packet method was applied to the larvae to test formulations 3 and 4 since the
      other two had already been tested before. Two control groups were established in
      both experiments; in one, ticks were treated with 1 % DMSO, and in the other,
      with 50 % ethanol, with ten repetitions for each treatment. The groups were
      maintained at 27+/-1  degrees C and RH>80 +/- 10 %. For engorged females, the
      parameters weight before oviposition, egg mass weight, hatching percentage of
      larvae, and percentage of control were evaluated, while for larvae, percentage of
      mortality was evaluated. The egg mass weight of all treatments differed
      significantly (p<0.05) from the control groups; however, the reduction in egg
      mass weight was more accentuated (p<0.05) in the treatments with formulations 1,
      3, and 4. The values of hatching percentage of the group treated with formulation
      2 and control group were statistically similar (p>0.05). The group treated with
      formulation 2 attained the lowest percentage of control (66 %). In the other
      treatments, the control percentages were greater than 99 %. In larval test, the
      mortality was 100 % in all the treatments, and there was no mortality in the
      control groups.

PMID- 24292542
TI  - Analysis of Glossina palpalis gambiensis and Glossina tachinoides from two
      distant locations in Burkina Faso using MALDI TOF MS.
AB  - Riverine tsetse (Glossina) as Glossina palpalis gambiensis Vanderplank 1949 and
      Glossina tachinoides Westwood 1850 are the main vectors for African animal
      trypanosomoses in Burkina Faso. Vector control has been proven efficient in
      disease containment, but its success is endangered by the reinvasion of tsetse
      from neighbouring areas. Thus, identifying relic populations can enhance the
      success rate of vector control efforts. This is currently carried out through
      microsatellite analysis which is time-consuming and costly. Recently, matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry-based
      analysis has become a routine method in microbial species identification. Owing
      to the rapidness and cost-effectiveness, this approach has been extended towards
      species identification of higher organisms such as tsetse. Following the recent
      experiences in distinguishing two genotypes of Prototheca spp., it is of interest
      to explore the validity of mass spectrometry for tsetse population
      differentiation. As a preliminary test, we submitted male and female G. palpalis
      gambiensis and G. tachinoides from Sideradougou and Folonzo, Burkina Faso
      (distance 60 km) to matrix-assisted laser desorption/ionisation analysis. The
      wing samples were utilized for protein extraction and mass spectra in a broad
      mass to charge ratio (2,000-20,000 kDa) were obtained. Specific peaks appeared to
      represent species, sex and location. Then, a peak list was extracted, containing
      the peaks in mass-to-charge ratio by revealing their intensities as well. These
      lists were used to compute a spectral dendrogram and a principle component
      analysis which displayed the differences among the samples from the two different
      regions. The results indicate that this technique can be extended with additional
      tsetse species, ideally with supporting genomic data, to later assist in
      designing rational vector control strategies.

PMID- 24292543
TI  - Prevalence and diversity of Encephalitozoon spp. and Enterocytozoon bieneusi in
      wild boars (Sus scrofa) in Central Europe.
AB  - From 2011 to 2012, the occurrence of Enterocytozoon bieneusi and Encephalitozoon
      spp. was surveyed at 29 randomly selected localities (both forest areas and
      enclosures) across four Central European countries: Austria, the Czech Republic,
      Poland, and the Slovak Republic. Isolates were genotyped by PCR amplification and
      characterization of the internal transcribed spacer (ITS) region using
      Enterocytozoon and Encephalitozoon-specific protocols. PCR revealed 16 mono
      infections of Encephalitozoon cuniculi, 33 mono-infections of Enterocytozoon
      bieneusi and 5 concurrent infections of both Encephalitozoon cuniculi and
      Enterocytozoon bieneusi out of 460 faecal samples. Two genotypes (I and II) were
      revealed by sequence analysis of the ITS region of Encephalitozoon cuniculi.
      Eleven genotypes, five previously found in other hosts including domestic pigs
      (D, EbpA, EbpC, G and Henan-I) and six novel (WildBoar1-6), were identified in
      Enterocytozoon bieneusi. No other microsporidia infection was found in the
      examined faecal samples. Prevalence of microsporidia at the locality level ranged
      from 0 to 58.8 %; the prevalence was less than 25 % at more than 86 % of
      localities. Enterocytozoon bieneusi was detected as a predominant species
      infecting Eurasian wild boars (Sus scrofa). The present report is the most
      comprehensive survey of microsporidia infections in wild boars within the Czech
      Republic and selected Central European countries.

PMID- 24292544
TI  - Design and development of aqueous nanoformulations for mosquito control.
AB  - Microemulsions (ME) are thermodynamically stable isotropic mixtures of oil,
      water, and surfactant; they would also be attractive as potential insecticidal
      products due to the high bioviability of the active ingredient, attributable to
      the small sizes of the oil drops. A laboratory study was conducted in order to
      compare the biological effect of oil in water (o/w) geranium essential oil (EO)
      and geraniol MEs and emulsions, against Culex pipiens pipiens mosquito larvae.
      The systems were based on three nonionic surfactants (Cremophor EL, Brij 35,
      Tween 80). The MEs showed dispersed phase diameters in the range of 8 to 14 nm
      and had low PDI values (<0.2). The MEs were analyzed by TEM, indicating that they
      had nearly spherical morphology. The microemulsified systems based on geranium EO
      and those of geraniol produced a notable increase of the larvicidal activity when
      compared with the respectably emulsions, concluding that the biological effect is
      related with the diameter of the dispersed phase. The smallest drops achieved the
      highest larvicidal activity, being the aqueous nanoformulations based on geraniol
      most effective than those of geranium EO. However, geranium microemulsions are
      preferred due to their residual toxicological profiles. The results indicate that
      these novel systems could be used in integrated pest management program for the
      C. pipiens pipiens.

PMID- 24292545
TI  - Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the
      treatment of toxoplasmosis.
AB  - We propose an innovative product based on the nanoencapsulation of pyrimethamine
      (PYR), aiming an improvement of drug efficacy for the treatment of toxoplasmosis.
      The in vitro cytotoxicity effect of encapsulated PYR and PYR-colloidal suspension
      was concomitantly evaluated against LLC-MK2 lineage and mouse peritoneal
      macrophage showing that the cells had similar tolerance for both PYR encapsulated
      or in the aqueous suspension. CF1 mice acutely infected with tachyzoites of
      Toxoplasma gondii RH strain treated with different doses (5.0-10 mg/kg/day) of
      PYR-nanocapsules had survival rate higher than the animals treated with the same
      doses of non-encapsulated PYR. Thus, encapsulation of PYR improved the efficacy
      of this drug against an acute model of toxoplasmosis in mice and can be
      considered an alternative for reducing the dose of PYR, which, in turn, could
      also reduce the side effects associated to the treatment.

PMID- 24292546
TI  - Association between serum ferritin levels and the incidence of obesity in Korean
      men: a prospective cohort study.
AB  - Elevated serum ferritin levels are associated with insulin resistance, type 2
      diabetes, cardiovascular disease, and metabolic syndrome. To date, however, no
      cohort studies have examined whether serum ferritin levels are an independent
      risk factor for the obesity. Therefore, we conducted a prospective cohort study
      to evaluate the temporal relationship between serum ferritin levels and obesity
      development in Korean men. Total 17,812 healthy Korean men who participated in a
      medical health check-up program in 2005 were followed-up until 2010. Obesity was
      defined as a body mass index >=25 kg/m(2). Cox proportional hazards model was
      used to measure the hazard ratio of the quartile groups of serum ferritin levels.
      During 64,446.5 person-years of follow-up carried out, 2,627 patients became
      obese. After adjusting for multiple covariates, we found that the hazard ratios
      (95% confidence interval) for incident obesity when we compared the second, third
      and fourth quartiles of serum ferritin levels with the first quartile were 1.08
      (0.95-1.23), 1.14 (1.00-1.30), and 1.24 (1.09-1.41), respectively (p for trend =
      0.003). Both severe obesity (body mass index >= 30 kg/m(2)) and abdominal obesity
      based on waist circumference (>90 cm) showed consistent longitudinal associations
      (p for trend <0.001). Elevated serum ferritin levels may have been a predictive
      factor for obesity during the 5-year follow-up in 17,812 Korean men. 

PMID- 24292548
TI  - Self-assembly of gold nanorods into vertically aligned, rectangular microplates
      with a supercrystalline structure.
AB  - Vertically aligned, supercrystalline microplates with a well-defined rectangular
      shape were fabricated in a large area through self-assembly of gold nanorods by a
      novel bulk solution evaporation method. This evaporative self-assembly strategy
      involving continuous movement of the contact line can prevent the coffee-ring
      effect, thus allowing uniform deposition of discrete GNR superstructures over a
      large area and favoring the formation of GNR supercrystals with geometrically
      symmetric shapes. A mechanism based on the continuing nucleation and growth of
      smectic GNR superstructures accompanying the movement of the contact line was put
      forward for the formation of the unique GNR supercrystal arrays. Based on this
      mechanism, a micropatterned substrate was designed to control the nucleation
      location and growth direction, leading to the spontaneous self-assembly of nearly
      parallel arrays of vertically aligned, supercrystalline microplates of GNRs. The
      obtained rectangular-plate-shaped GNR supercrystals exhibited interesting
      anisotropic optical reflection properties, which were revealed by polarized light
      microscopy. 

PMID- 24292547
TI  - Involvement of larder beetles (Coleoptera: Dermestidae) on human cadavers: a
      review of 81 forensic cases.
AB  - From 1994 to 2013, French forensic entomology laboratories investigated 1,093
      cases. Larder beetles (Coleoptera: Dermestidae) were observed in 81 (7.5%) of
      these cases. To describe and analyze these 81 cases, eight parameters were used:
      city, location (indoor or outdoor), decay stage (fresh, decay, or dry), dermestid
      species and instar (adults and/or larvae), presence of living calliphorid larvae,
      presence of calliphorid pupae or adults, and presence of other necrophagous
      species. Eight Dermestidae species were observed: Dermestes frischii (42% of
      cases), Dermestes undulatus (35.8%), Dermestes peruvianus (12.3%), Dermestes
      lardarius (9.9%), Dermestes haemorrhoidalis (8.6%), Dermestes maculatus (7.4%),
      Dermestes bicolor (3.7%), and Dermestes ater (1.2%). Larder beetles primarily
      developed on human cadavers in outdoor locations in areas with a dry climate and
      were never reported in oceanic areas (which are characterized by frequent
      rainfall and high ambient humidity). The number of dermestid species on a single
      corpse never exceeded three. Typically, one species was found per corpse. Species
      differed between indoor and outdoor cases, with D. frischii and D. undulatus
      dominant in outdoor cases, while D. peruvianus dominant in indoor cases.
      Calliphoridae was found in 88% of the cases, while Hydrotaea and Piophilidae were
      observed 40% of the time. Regarding Coleoptera, Necrobia spp. (Coleoptera:
      Cleridae) was observed in 46% of the cases. Lastly, we observed a typical
      decomposition pattern, with preferential feeding areas on the face, hands, and
      feet (i.e., the extremities). Pupation chambers on or inside the bones were not
      observed.

PMID- 24292550
TI  - Healthy ageing and regenerative medicine.

PMID- 24292551
TI  - Nanoscale resolution scanning thermal microscopy using carbon nanotube tipped
      thermal probes.
AB  - We present an experimental proof of concept of scanning thermal nanoprobes that
      utilize the extreme thermal conductance of carbon nanotubes (CNTs) to channel
      heat between the probe and the sample. The integration of CNTs into scanning
      thermal microscopy (SThM) overcomes the main drawbacks of standard SThM probes,
      where the low thermal conductance of the apex SThM probe is the main limiting
      factor. The integration of CNTs (CNT-SThM) extends SThM sensitivity to thermal
      transport measurement in higher thermal conductivity materials such as metals,
      semiconductors and ceramics, while also improving the spatial resolution.
      Investigation of thermal transport in ultra large scale integration (ULSI)
      interconnects, using the CNT-SThM probe, showed fine details of heat transport in
      ceramic layers, vital for mitigating electromigration in ULSI metallic current
      leads. For a few layer graphene, the heat transport sensitivity and spatial
      resolution of the CNT-SThM probe demonstrated significantly superior thermal
      resolution compared to that of standard SThM probes achieving 20-30 nm topography
      and ~30 nm thermal spatial resolution compared to 50-100 nm for standard SThM
      probes. The outstanding axial thermal conductivity, a high aspect ratio and
      robustness of CNTs can make CNT-SThM the perfect thermal probe for the
      measurement of nanoscale thermophysical properties and an excellent candidate for
      the next generation of thermal microscopes.

PMID- 24292553
TI  - Learning from unbalanced data: a cascade-based approach for detecting clustered
      microcalcifications.
AB  - Finding abnormalities in diagnostic images is a difficult task even for expert
      radiologists because the normal tissue locations largely outnumber those with
      suspicious signs which may thus be missed or incorrectly interpreted. For the
      same reason the design of a Computer-Aided Detection (CADe) system is very
      complex because the large predominance of normal samples in the training data may
      hamper the ability of the classifier to recognize the abnormalities on the
      images. In this paper we present a novel approach for computer-aided detection
      which faces the class imbalance with a cascade of boosting classifiers where each
      node is trained by a learning algorithm based on ranking instead of
      classification error. Such approach is used to design a system (CasCADe) for the
      automated detection of clustered microcalcifications (MUCs), which is a severely
      unbalanced classification problem because of the vast majority of image locations
      where no MUC is present. The proposed approach was evaluated with a dataset of
      1599 full-field digital mammograms from 560 cases and compared favorably with the
      Hologic R2CAD ImageChecker, one of the most widespread commercial CADe systems.
      In particular, at the same lesion sensitivity of R2CAD (90%) on biopsy proven
      malignant cases, CasCADe and R2CAD detected 0.13 and 0.21 false positives per
      image (FPpi), respectively (p-value=0.09), whereas at the same FPpi of R2CAD
      (0.21), CasCADe and R2CAD detected 93% and 90% of true lesions respectively (p
      value=0.11) thus showing that CasCADe can compete with high-end CADe commercial
      systems. 

PMID- 24292552
TI  - New viruses for cancer therapy: meeting clinical needs.
AB  - Early-stage clinical trials of oncolytic virotherapy have reported the safety of
      several virus platforms, and viruses from three families have progressed to
      advanced efficacy trials. In addition, preclinical studies have established proof
      of-principle for many new genetic engineering strategies. Thus, the virotherapy
      field now has available a diverse collection of viruses that are equipped to
      address unmet clinical needs owing to improved systemic administration, greater
      tumour specificity and enhanced oncolytic efficacy. The current key challenge for
      the field is to develop viruses that replicate with greater efficiency within
      tumours while achieving therapeutic synergy with currently available treatments. 

PMID- 24292554
TI  - Contour tracking in echocardiographic sequences via sparse representation and
      dictionary learning.
AB  - This paper presents a dynamical appearance model based on sparse representation
      and dictionary learning for tracking both endocardial and epicardial contours of
      the left ventricle in echocardiographic sequences. Instead of learning offline
      spatiotemporal priors from databases, we exploit the inherent spatiotemporal
      coherence of individual data to constraint cardiac contour estimation. The
      contour tracker is initialized with a manual tracing of the first frame. It
      employs multiscale sparse representation of local image appearance and learns
      online multiscale appearance dictionaries in a boosting framework as the image
      sequence is segmented frame-by-frame sequentially. The weights of multiscale
      appearance dictionaries are optimized automatically. Our region-based level set
      segmentation integrates a spectrum of complementary multilevel information
      including intensity, multiscale local appearance, and dynamical shape prediction.
      The approach is validated on twenty-six 4D canine echocardiographic images
      acquired from both healthy and post-infarct canines. The segmentation results
      agree well with expert manual tracings. The ejection fraction estimates also show
      good agreement with manual results. Advantages of our approach are demonstrated
      by comparisons with a conventional pure intensity model, a registration-based
      contour tracker, and a state-of-the-art database-dependent offline dynamical
      shape model. We also demonstrate the feasibility of clinical application by
      applying the method to four 4D human data sets. 

PMID- 24292555
TI  - ER stress does not cause upregulation and activation of caspase-2 to initiate
      apoptosis.
AB  - A recent report claimed that endoplasmic reticulum (ER) stress activates the ER
      trans-membrane receptor IRE1alpha, leading to increased caspase-2 levels via
      degradation of microRNAs, and consequently induction of apoptosis. This
      observation casts caspase-2 into a central role in the apoptosis triggered by ER
      stress. We have used multiple cell types from caspase-2-deficient mice to test
      this hypothesis but failed to find significant impact of loss of caspase-2 on ER
      stress-induced apoptosis. Moreover, we did not observe increased expression of
      caspase-2 protein in response to ER stress. Our data strongly argue against a
      critical role for caspase-2 in ER-stress-induced apoptosis. 

PMID- 24292556
TI  - Splicing factor SRSF3 represses the translation of programmed cell death 4 mRNA
      by associating with the 5'-UTR region.
AB  - Serine/arginine-rich splicing factor 3 (SRSF3), a member of the serine/arginine
      (SR)-rich family of proteins, regulates both alternative splicing of pre-mRNA and
      export of mature mRNA from the nucleus. Although its role in nuclear mRNA
      processing is well understood, the mechanism by which it alters the fate of
      cytoplasmic mRNA molecules remains elusive. Here, we provide evidence that SRSF3
      not only regulates the alternative splicing pattern of programmed cell death 4
      (PDCD4) mRNA, but also modulates its translational efficiency in the cytoplasm by
      lowering translation levels. We observed a marked increase in PDCD4 mRNA in
      translating polysome fractions upon silencing of SRSF3, and, conversely, ectopic
      overexpression of SRSF3 shifted PDCD4 mRNA into non-translating ribosomal
      fractions. In live cells, SRSF3 colocalized with PDCD4 mRNA in P-bodies (PBs),
      where translationally silenced mRNAs are deposited, and this localization was
      abrogated upon SRSF3 silencing. Furthermore, using two different reporter
      systems, we showed that SRSF3 interacts directly with PDCD4 mRNA and mediates
      translational repression by binding to the 5'-untranslated region (5'-UTR). In
      summary, our data suggest that the oncogenic potential of SRSF3 might be
      realized, in part, through the translational repression of PDCD4 mRNA. 

PMID- 24292557
TI  - Effect of remote ischaemic conditioning on contrast-induced nephropathy in
      patients undergoing elective coronary angiography (ERICCIN): rationale and study
      design of a randomised single-centre, double-blind placebo-controlled trial.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN), an acute kidney injury resulting
      from the administration of intravascular iodinated contrast media, is an
      important cause of morbidity/mortality following coronary angiographic procedures
      in high-risk patients. Despite preventative measures intended to mitigate the
      risk of CIN, there remains a need for an effective intervention. Remote ischaemic
      conditioning (RIC), where non-injurious ischaemia is applied to an arm prior to
      the administration of contrast, has shown promise in attenuating CIN but its
      effectiveness in preserving long-term renal function is unknown, which will be
      studied as part of the effect of remote ischaemic conditioning against contrast
      induced nephropathy (ERICCIN) trial. ( http://Controlled-trials.com Identifier:
      ISRCTN49645414.) METHODS: The ERICCIN trial is a single-centre, randomised double
      blinded placebo-controlled trial which plans to recruit 362 patients who are at
      risk of CIN, defined by pre-existent renal impairment (estimated glomerular
      filtration rate <60 ml/min/1.73 m2), over a period of 2 years. Patients will be
      randomised to either control or RIC consisting of 4, 5 min 200 mmHg balloon-cuff
      inflation/deflations, to the upper arm. The primary endpoint will be the
      development of CIN (>25% of eGFR, or rise of creatinine of >44 MUmol/l) at 48 h.
      A key secondary endpoint will be whether RIC impacts upon persistent renal
      impairment over the 3-month follow-up period. Additional secondary endpoints
      include the measurement of serum neutrophil gelatinase-associated lipocalin and
      urinary albumin at 6, 48 h and 3 months following administration of contrast.
      IMPLICATIONS: Findings from ERICCIN trial will potentially demonstrate that RIC
      attenuates contrast-induced acute and chronic kidney injury and influence future
      clinical practice guidelines in at-risk patients undergoing coronary angiographic
      procedures.

PMID- 24292558
TI  - Reversion of DNA strand displacement using functional nucleic acids as toeholds.
AB  - Herein we report the reversion of DNA strand displacement using functional
      nucleic acids as toeholds. 

PMID- 24292559
TI  - Integrated IMR for psychiatric and general medical illness for adults aged 50 or
      older with serious mental illness.
AB  - OBJECTIVES: Self-management is promoted as a strategy for improving outcomes for
      serious mental illness as well as for chronic general medical conditions. This
      study evaluated the feasibility and effectiveness of an eight-month program
      combining training in self-management for both psychiatric and general medical
      illness, including embedded nurse care management. METHODS: Participants were 71
      middle-aged and older adults (mean age=60.3 +/- 6.5) with serious mental illness
      and chronic general medical conditions who were randomly assigned to receive
      integrated Illness Management and Recovery (I-IMR) (N=36) or usual care (N=35).
      Feasibility was determined by attendance at I-IMR and nurse sessions.
      Effectiveness outcomes were measured two and six months after the intervention
      (ten- and 14-month follow-ups) and included self-management of psychiatric and
      general medical illness, participation in psychiatric and general medical
      encounters, and self-reported acute health care utilization. RESULTS: I-IMR
      participants attended 15.8 +/- 9.5 I-IMR and 8.2 +/- 5.9 nurse sessions, with 75%
      attending at least ten I-IMR and five nurse sessions. Compared with usual care, I
      IMR was associated with greater improvements in participant and clinician ratings
      for psychiatric illness self-management, greater diabetes self-management, and an
      increased preference for detailed diagnosis and treatment information during
      primary care encounters. The proportion of I-IMR participants with at least one
      psychiatric or general medical hospitalization decreased significantly between
      baseline and ten- and 14-month follow-ups. CONCLUSIONS: I-IMR is a feasible
      intervention for this at-risk group and demonstrated potential effectiveness by
      improving self-management of psychiatric illness and diabetes and by reducing the
      proportion of participants requiring psychiatric or general medical
      hospitalizations.

PMID- 24292560
TI  - Alemtuzumab in chronic lymphocytic leukemia: final results of a large
      observational multicenter study in mostly pretreated patients.
AB  - This retrospective study evaluated the benefit of alemtuzumab monotherapy in
      unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and
      prolymphocytic leukemia (B-PLL) to definitely describe the impact of this
      antibody in clinical routine use. Data were collected from 208 consecutive,
      mainly pretreated, patients with CLL (n = 202), and B-PLL (n = 6) who had
      received alemtuzumab. Response, progression-free survival (PFS), and overall
      survival (OS) in various settings were assessed, and toxicities were documented.
      In these routine patients, a comparably low cumulative dose of alemtuzumab
      (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various
      pre-therapeutic parameters were predictive for inferior response, among them, the
      prior administration of >=3 therapy lines (P < 0.001), refractoriness to
      fludarabine (P = 0.002), and bulky lymphadenopathy (P = 0.003). PFS and OS after
      start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky
      lymphadenopathy was the prominent risk factor for both inferior PFS (P < 0.001)
      and OS (P = 0.002). In B-PLL, four patients experienced a fatal outcome, whereas
      two patients had some benefit with alemtuzumab. The main adverse effects were CMV
      reactivation (20 %) and a broad spectrum of infections, which together were the
      main reasons for treatment interruption and/or premature termination. In
      conclusion, alemtuzumab administered even at low dose levels was effective but
      overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab
      remains an important therapeutic option in subsets of CLL patients.

PMID- 24292561
TI  - Effectiveness of treatment of iron deficiency anemia in rats with squid ink
      melanin-Fe.
AB  - Iron deficiency anemia (IDA) is the one of the most common nutritional problems
      and is encountered all over the world. This study analysed the effects of squid
      ink melanin-Fe (SM-Fe) on IDA in rats. Forty weanling SD male rats were used and
      thirty-two rats were fed an iron-deficient diet for 4 weeks. Then SM-Fe (dosages
      of iron is 6 mg kg(-1) BW) was given to the IDA rats once a day for 3 weeks by
      intragastric administration, with FeCl3 and FeSO4 (dosages of iron is 6 mg kg(-1)
      BW) as positive controls. While the IDA model group and the control group were
      administrated distilled deionized water each day for 3 weeks. The content of
      haemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC), serum
      ferritin (SF), transferrin receptor (sTfR), erythropoietin (EPO), and iron
      content in the liver and spleen were measured. The results showed that the
      content of Hb, SI, SF, EPO, iron content in the liver and spleen were
      significantly increased in the iron supplement groups (SM-Fe, FeCl3 and FeSO4)
      compared with the model group (P < 0.05), while TIBC and sTfR were significantly
      decreased in the iron supplement groups compared with the model group (P < 0.05).
      In comparison with the FeCl3 and FeSO4 groups, a higher bioavailability of iron
      and fewer side effects were observed in the SM-Fe group. The present study
      indicated that SM-Fe is an effective source of iron supplement for IDA rats and
      might be exploited as a new iron fortifier. 

PMID- 24292562
TI  - On flat objects of finitely accessible categories.
AB  - Flat objects of a finitely accessible additive category C are described in terms
      of some objects of the associated functor category of C, called strongly flat
      functors. We study closure properties of the class of strongly flat functors, and
      we use them to deduce the known result that every object of a finitely accessible
      abelian category has a flat cover.

PMID- 24292563
TI  - Analysis of Chinese hamster ovary cell metabolism through a combined
      computational and experimental approach.
AB  - Optimization of cell culture processes can benefit from the systematic analysis
      of experimental data and their organization in mathematical models, which can be
      used to decipher the effect of individual process variables on multiple outputs
      of interest. Towards this goal, a kinetic model of cytosolic glucose metabolism
      coupled with a population-level model of Chinese hamster ovary cells was used to
      analyse metabolic behavior under batch and fed-batch cell culture conditions. The
      model was parameterized using experimental data for cell growth dynamics,
      extracellular and intracellular metabolite profiles. The results highlight
      significant differences between the two culture conditions in terms of metabolic
      efficiency and motivate the exploration of lactate as a secondary carbon source.
      Finally, the application of global sensitivity analysis to the model parameters
      highlights the need for additional experimental information on cell cycle
      distribution to complement metabolomic analyses with a view to parameterize
      kinetic models. 

PMID- 24292564
TI  - Attenuation of flightless I improves wound healing and enhances angiogenesis in a
      murine model of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Skin lesions and ulcerations are severe complications of
      diabetes that often result in leg amputations. In this study we investigated the
      function of the cytoskeletal protein flightless I (FLII) in diabetic wound
      healing. We hypothesised that overexpression of FLII would have a negative effect
      on diabetic wound closure and modulation of this protein using specific FLII
      neutralising antibodies (FnAb) would enhance cellular proliferation, migration
      and angiogenesis within the diabetic wound. METHODS: Using a streptozotocin
      induced model of diabetes we investigated the effect of altered FLII levels
      through Flii genetic knockdown, overexpression or treatment with FnAb on wound
      healing. Diabetic wounds were assessed using histology, immunohistochemistry and
      biochemical analysis. In vitro and in vivo assays of angiogenesis were used to
      assess the angiogenic response. RESULTS: FLII levels were elevated in the wounds
      of both diabetic mice and humans. Reduction in the level of FLII improved healing
      of murine diabetic wounds and promoted a robust pro-angiogenic response with
      significantly elevated von Willebrand factor (vWF) and vascular endothelial
      growth factor (VEGF)-positive endothelial cell infiltration. Diabetic mouse
      wounds treated intradermally with FnAb showed improved healing and a
      significantly increased rate of re-epithelialisation. FnAb improved the
      angiogenic response through enhanced formation of capillary tubes and functional
      neovasculature. Reducing the level of FLII led to increased numbers of mature
      blood vessels, increased recruitment of smooth muscle actin-alpha-positive cells
      and improved tight junction formation. CONCLUSIONS/INTERPRETATION: Reducing the
      level of FLII in a wound may be a potential therapeutic approach for the
      treatment of diabetic foot ulcers.

PMID- 24292565
TI  - Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and
      infant death: a population-based study.
AB  - AIMS/HYPOTHESIS: Pre-existing diabetes is associated with an increased risk of
      stillbirth, but few studies have excluded the effect of congenital anomalies.
      This study used data from a long-standing population-based survey of women with
      pre-existing diabetes to investigate the risks of fetal and infant death and
      quantify the contribution of glycaemic control. METHODS: All normally formed
      singleton offspring of women with pre-existing diabetes (1,206 with type 1
      diabetes and 342 with type 2 diabetes) in the North of England during 1996-2008
      were identified from the Northern Diabetes in Pregnancy Survey. RRs of fetal
      death (>=20 weeks of gestation) and infant death were estimated by comparison
      with population data from the Northern Perinatal Morbidity and Mortality Survey.
      Predictors of fetal and infant death in women with pre-existing diabetes were
      examined by logistic regression. RESULTS: The prevalence of fetal death in women
      with diabetes was over four times greater than in those without (RR 4.56 [95% CI
      3.42, 6.07], p < 0.0001), and for infant death it was nearly doubled (RR 1.86
      [95% CI 1.00, 3.46], p = 0.046). There was no difference in the prevalence of
      fetal death (p = 0.51) or infant death (p = 0.70) between women with type 1
      diabetes and women with type 2 diabetes. There was no evidence that the RR of
      fetal and infant death had changed over time (p = 0.95). Increasing
      periconception HbA1c concentration above 49 mmol/mol (6.6%) (adjusted odds ratio
      [aOR] 1.02 [95% CI 1.00, 1.04], p = 0.01), prepregnancy retinopathy (aOR 2.05
      [95% CI 1.04, 4.05], p = 0.04) and lack of prepregnancy folic acid consumption
      (aOR 2.52 [95% CI 1.12, 5.65], p = 0.03) were all independently associated with
      increased odds of fetal and infant death. CONCLUSIONS/INTERPRETATION: Pre
      existing diabetes is associated with a substantially increased risk of fetal and
      infant death in normally formed offspring, the effect of which is largely
      moderated by glycaemic control.

PMID- 24292566
TI  - Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of
      hepatocytes via the S1P2 receptor subtype.
AB  - AIMS/HYPOTHESIS: Enhanced plasma levels of NEFA have been shown to induce hepatic
      insulin resistance, which contributes to the development of type 2 diabetes.
      Indeed, sphingolipids can be formed via a de novo pathway from the saturated
      fatty acid palmitate and the amino acid serine. Besides ceramides, sphingosine 1
      phosphate (S1P) has been identified as a major bioactive lipid mediator.
      Therefore, our aim was to investigate the generation and function of S1P in
      hepatic insulin resistance. METHODS: The incorporation of palmitate into
      sphingolipids was performed by rapid-resolution liquid chromatography-MS/MS in
      primary human and rat hepatocytes. The influence of S1P and the involvement of
      S1P receptors in hepatic insulin resistance was examined in human and rat
      hepatocytes, as well as in New Zealand obese (NZO) mice. RESULTS: Palmitate
      induced an impressive formation of extra- and intracellular S1P in rat and human
      hepatocytes. An elevation of hepatic S1P levels was observed in NZO mice fed a
      high-fat diet. Once generated, S1P was able, similarly to palmitate, to
      counteract insulin signalling. The inhibitory effect of S1P was abolished in the
      presence of the S1P2 receptor antagonist JTE-013 both in vitro and in vivo. In
      agreement with this, the immunomodulator FTY720-phosphate, which binds to all S1P
      receptors except S1P2, was not able to inhibit insulin signalling.
      CONCLUSIONS/INTERPRETATION: These data indicate that palmitate is metabolised by
      hepatocytes to S1P, which acts via stimulation of the S1P2 receptor to impair
      insulin signalling. In particular, S1P2 inhibition could be considered as a novel
      therapeutic target for the treatment of insulin resistance.

PMID- 24292569
TI  - Establishment of human retinal microvascular endothelial cells with extended life
      span.
AB  - AIM: To generate and characterize a telomerase-immortalized human retinal
      microvascular endothelial cell (HREC) line. This cell line may be utilized as an
      in vitro model to study the molecular basis of several diseases of the human
      retina. MATERIALS AND METHODS: Primary retinal neuronal cells were isolated and
      transfected with plasmid encoding full-length human telomerase reverse
      transcriptase (hTERT). Transfected cells were selected and characterized to
      determine telomerase activity, karyotype, proliferative capacity and
      functionality. RESULTS: HREC-hTERT cells appear morphologically similar to
      primary endothelial cells and have an extended in vitro life-span. HREC-hTERT
      cells express the progenitor/stem cell marker nestin. They have active telomerase
      and a high proliferative capacity. These cells also maintain a diploid karyotype.
      The HREC-hTERT cells showed high colony-formation capacity and plating efficiency
      compared to the primary cells. These cells are capable of differentiation into
      neuronal and glial cell phenotypes and the differentiated cells express the
      astrocyte marker glial fibrillary acidic protein (GFAP) and the neuronal marker
      microtubule-associated protein-2 (MAP2), respectively. CONCLUSION: The in vitro
      life-span of human retinal neuronal endothelial cells can be extended by ectopic
      expression of hTERT without altering the genetic stability and functionality of
      these cells. These cells will be a valuable tool to further our understanding on
      the role of HRECs in the human blood-retinal-barrier and in angiogenesis and
      neovascularization.

PMID- 24292570
TI  - Low-dose radiation modifies skin response to acute gamma-rays and protons.
AB  - The goal of the present study was to obtain pilot data on the effects of
      protracted low-dose/low-dose-rate (LDR) gamma-rays on the skin, both with and
      without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were
      examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f)
      LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h),
      whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min,
      respectively). Assays were performed 56 days after exposure. Skin samples from
      all irradiated groups had activated caspase-3, indicative of apoptosis. The
      significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups
      were not present when LDR pre-exposure was included. However, the terminal
      deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation
      and histological examination of hematoxylin and eosin-stained sections revealed
      no significant differences among groups, regardless of radiation regimen. The
      data demonstrate that caspase-3 activation initially triggered by both forms of
      acute radiation was greatly elevated in the skin nearly two months after whole
      body exposure. In addition, LDR gamma-ray priming ameliorated this response. 

PMID- 24292571
TI  - The chorioallantoic membrane assay is a promising ex vivo model system for the
      study of vascular anomalies.
AB  - The present feasibility study evaluated the chorioallantoic membrane (CAM) assay
      established in cancer and angiogenesis research as a tool for the study of
      vascular anomalies (VAs) in the head and neck area, since the lack of appropriate
      model systems poses a major obstacle in VA research. MATERIALS AND METHODS: VA
      tissues from three patients, two with an arteriovenous and one with a lymphatic
      malformation, were analyzed and evaluated in the CAM assay. RESULTS: The
      arteriovenous malformations induced a potent angiogenic reaction, resulting in
      new vessel growth and reperfusion by chicken embryo blood, which was comparable
      in extent with the positive vascular endothelial growth factor control. An
      angiogenic reaction, although less pronounced, was also observed in the single
      tested lymphatic malformation. CONCLUSION: Our observations indicate the CAM
      assay to be a suitable model system for the study of VAs, as well as to show how
      treatment with pro- and antiangiogenic drugs affects VA growth patterns. The CAM
      assay has the potential to become a valuable tool for VA studies.

PMID- 24292568
TI  - Role of cytokines as a double-edged sword in sepsis.
AB  - BACKGROUND: Sepsis is a deadly immunological disorder and its pathophysiology is
      still poorly understood. We aimed to determine if specific pro-inflammatory and
      anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for
      sepsis. MATERIALS AND METHODS: Recent publications in the MEDLINE database were
      searched for articles regarding the clinical significance of inflammatory
      cytokines in sepsis. RESULTS: In response to pathogen infection, pro-inflammatory
      cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-alpha (TNF
      alpha)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis.
      Importantly, a decrease in IL-6 was associated with a better prognosis and
      overproduction of IL-10 was found to be the main predictor of severity and fatal
      outcome. CONCLUSION: Both pro-inflammatory and anti-inflammatory cytokines
      constitute a double-edged sword in sepsis; on one hand they are critical to
      eliminate the infection while on the other, excessive production can cause tissue
      and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF
      alpha may have implications in diagnosis and treatment of sepsis.

PMID- 24292572
TI  - Baicalin scavenges reactive oxygen species and protects human keratinocytes
      against UVC-induced cytotoxicity.
AB  - Long-term exposure to solar ultraviolet (UV) radiation can cause multiple skin
      disorders, including skin cancer. Protection against UV-induced damage is,
      therefore, a worldwide concern. Baicalin, a major component of traditional
      Chinese medicine Scutellaria baicalensis, has been reported to have antioxidant
      and cytostatic effects on normal epithelial and normal peripheral blood and
      myeloid cells. In the current study, we examined whether baicalin could also
      effectively protect human keratinocytes from damaging short-wave UVC irradiation.
      Baicalin-scavenged reactive oxygen species increased within 2 h after UVC
      radiation. Baicalin also abrogated UVC-induced apoptosis. In addition, we
      identified the major products after UVC radiation with T4 UV endonuclease,
      finding that baicalin prevented cyclobutane pyrimidine dimer formation induced by
      UVC. Furthermore, baicalin also prevented formation of oxidative adducts induced
      by UVC. Our results demonstrated the utility of baicalin in assessing the
      potential contribution of traditional Chinese medicinal agents in therapy of UVC
      induced genomic damage to skin and suggest potential application of these agents
      as pharmaceuticals in prevention of solar-induced skin damage. 

PMID- 24292573
TI  - Systemic and neuronal inflammatory markers in a mouse model of mevalonate kinase
      deficiency: a strain-comparative study.
AB  - BACKGROUND/AIM: There is a lack of reliable animal models for the study of the
      rare auto-inflammatory disease mevalonate kinase deficiency (MKD). The one most
      frequently used is a biochemical model, obtained by treating BALB/c mice in order
      to block the mevalonate pathway, thus attempting to reproduce the inflammatory
      pattern presented in patients. This study aims to assess the role played in
      pathology by the inflammasome and the reliability of this model. MATERIALS AND
      METHODS: We mimicked MKD using two different mice strains (BALB/c and C57BL/6),
      evaluating typical inflammatory markers of MKD and inflammasome modulation.
      RESULTS: Without significant differences, both strains exhibited a general MKD
      like inflammation, including the modulation of the molecular platform
      inflammasome, mimicking the characteristics observed in human patients.
      CONCLUSION: Although with some limitations, the mouse model appears robust and
      suitable for studying MKD. Results do not seem to vary with the mouse strain
      used, and appear to be treatment-dependent. Finally, in vivo inflammasome
      activation was assessed for the first time here.

PMID- 24292574
TI  - B-scan ultrasonographic monitoring of orthotopic xenografted plexiform
      neurofibroma in mice.
AB  - BACKGROUND/AIM: Xenografted benign tumours in immunodeficient mice provide an in
      vivo model to study tumour biology and the effect of agents on tumour growth.
      Conventionally, these small grafts can only be monitored upon sacrificing the
      animals. We evaluated ultrasound biomicroscopy for monitoring such grafts in
      vivo. MATERIALS AND METHODS: Small fragments (<10 mm(3)) of a plexiform
      neurofibroma obtained from patients with established diagnosis of
      neurofibromatosis type-1 (NF1) were orthotopically-xenografted onto the sciatic
      nerve of immunodeficient mice and monitored using a high-resolution in vivo micro
      imaging system. RESULTS: Grafts were identified in most cases and were
      distinguished from the surrounding inflammatory host tissues by detailed
      ultrasonographic signals. Graft sizes could be calculated precisely from serial
      scan sections and monitored during the whole course of drug treatment.
      CONCLUSION: High frequency sonographic measurement is a superior non-invasive
      method for monitoring small grafts of slowly growing benign tumours in mice in
      vivo, e.g. plexiform neurofibroma, and is especially suitable for tracing the
      effects of drugs at multiple time-points, thus allowing a very cost-effective
      follow-up.

PMID- 24292575
TI  - Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0
      mouse melanoma cells.
AB  - In a previous study performed by our group, we demonstrated that the water
      extract of Cordyceps sinensis (WECS) significantly prevented tumor metastasis
      from the spleen to the liver, using B16-F0 mouse melanoma cells as a model. In
      this study, we investigated the anti-metastatic activity of cordycepin (3'
      deoxyadenosine), one of the components of WECS, using an identical model of mice
      injected with B16-F0 cells into the spleen. All mice inoculated with B16-F0 cells
      died due to liver metastases via the portal vein from the spleen. Control mice
      not administered cordycepin exhibited higher serum levels of alanine
      aminotransferase (ALT) due to damage to the liver by metastasized B16-F0 cells
      from the spleen, and survival times ranged from 17 to 22 days after tumor
      inoculation. Cordycepin was intraperitoneally administered to mice, and resulted
      in significantly lower serum ALT levels and longer survival times than those
      observed in control mice. Taken together, these results indicate that cordycepin
      may be the active ingredient in C. sinensis exerting an anti-metastatic effect,
      and may be a potential candidate anti-metastatic agent. 

PMID- 24292576
TI  - Wogonin, a natural and biologically-active flavonoid, influences a murine WEHI-3
      leukemia model in vivo through enhancing populations of T- and B-cells.
AB  - Wogonin, a natural and biologically-active flavonoid found in plants, has been
      reported to exhibit anticancer effects on several cancer cell types. However,
      there is no available information regarding the responses to wogonin in leukemia
      mouse models. At concentrations of 10-200 MUM, wogonin reduced the percentage of
      viable WEHI-3 cells in a concentration-dependent manner. In an in vivo study,
      WEHI-3 cells were intraperitoneally injected into normal BALB/c mice for
      establishing leukemic BALB/c mice to determine the anti-leukemia activity of
      wogonin. Wogonin increased the survival rate and the body weight of leukemic mice
      when compared to vehicle (olive oil)-treated groups. Furthermore, the results
      also revealed that wogonin increased the percentage of cluster of differentiation
      3 CD3 (T-cell marker) and CD19 (B-cell marker) but reduced that of Mac-3
      (macrophages) and CD11b (monocytes) cell surface markers in treated mice as
      compared with the untreated leukemia group. Based on these observations, wogonin
      might exhibit anti-leukemia effects on murine WEHI-3 cell line-induced leukemia
      in vivo. 

PMID- 24292577
TI  - Toxicological evaluation of Antrodia cinnamomea in BALB/c mice.
AB  - Antrodia cinnamomea is a natural component of some herbal medicines used for
      treatment of abdominal pain, hypertension and hepatocellular carcinoma in Taiwan
      and other countries. Subchronic oral toxicity studies of A. cinnamomea extracts
      in male and female BALB/c mice were performed to evaluate its safety. Three
      different concentrations of A. cinnamomea (16.67, 833.3 and 1666.67 mg/kg/day)
      were given orally to groups of mice (10 mice/dose) for 90 consecutive days. All
      animals survived to the end of the study, and there were no significant
      differences in body weight among the control and treatment groups. No significant
      differences were found in hematological and serum biochemical parameters among
      the control and treatment groups. No abnormalities of internal organs were
      observed in the treated groups. 

PMID- 24292578
TI  - Photodynamic diagnosis of colitis-associated dysplasia in a mouse model after
      oral administration of 5-aminolevulinic acid.
AB  - BACKGROUND: Detection of dysplastic lesions in mouse colonic tissue was
      investigated by accumulation of photosensitizer protoporphyrin IX (PpIX) induced
      by oral administration of 5-aminolevulinic acid (5-ALA), a precursor of PplX.
      MATERIALS AND METHODS: Inflammatory oncogenesis was induced in C57BL/6J-Apc(Min)
      (Apc(Min/+)) mouse by oral administration of dextran sodium sulfate (DSS). After
      oral administration of 5-ALA, the colonic tissue was observed by autofluorescent
      stereoscopy and histopathological examination. The localization of fluorescence
      signals in the colonic tissue was determined with a mobile ultraviolet Xe lamp
      light. RESULTS: Several small polypoid lesions were found in the mucosal layer of
      DSS-treated Apc(Min/+) mice. Strong reddish ring-shaped fluorescence signals of
      PpIX, at 635 nm measured by a spectrum analyzer, were observed on the mucosal
      surface of all protruding lesions that were confirmed to be histopathologically
      dysplastic. CONCLUSION: Photodynamic diagnosis with 5-ALA was useful in detecting
      dysplastic lesions in the colonic mucosa in a mouse model.

PMID- 24292579
TI  - Healing effect of acellular dermal matrixes for repair of abdominal wall defects
      in a rat model.
AB  - BACKGROUND: Although acellular dermal matrix (ADM) is a widely used graft
      material for abdominal wall repair, differences in processing methods might yield
      different healing activities. The aim of this study was to compare the healing
      effects of two human-derived ADM prototypes in abdominal wall reconstruction.
      MATERIALS AND METHODS: A standardized 15*50 mm abdominal wall defect was created
      in 28 Sprague-Dawley rats, which were then implanted with either an EDTA-treated
      ADM prototype or a salt/solvent-treated ADM prototype. Adhesion formation,
      tensile strength, tissue ingrowth, neovascularization and inflammatory cell
      infiltration were then assessed in the two ADM prototypes during the experimental
      period. RESULTS: In both ADM prototypes, mild adhesion formation with the omentum
      was observed at autopsy at one and four weeks post-implantation. Tensile strength
      was higher at four weeks post-implantation than that at one week post
      implantation. Good neovascularization was observed in the periphery of the ADM,
      but not in the ADM core. Muscles facing the ADM and muscle-ADM junctions were
      thick and long at one week post-implantation and had been replaced by new host
      collagen at four weeks post-implantation. No mesothelial cells at the margins
      were observed at one and four weeks post-implantation. The thickness of the
      remaining implanted ADM at four weeks post-implantation was less than that at one
      week post-implantation. There were no statistical differences between the two ADM
      prototypes in terms of adhesion formation, tensile strength, tissue ingrowth,
      neovascularization and inflammatory cell infiltration during the experimental
      period. CONCLUSION: These results indicate that both ADM prototypes are
      applicable implant materials for repair of abdominal wall defects.

PMID- 24292580
TI  - Distribution changes of epithelial dendritic cells in canine cornea and mucous
      membranes related to hematopoietic stem cell transplantation.
AB  - BACKGROUND/AIM: Dendritic cells (DCs) are important immune mediators following
      allogeneic hematopoietic stem cell transplantation (HSCT). We screened for DC
      frequency in the cornea and oral mucous membranes after HSCT by confocal laser
      scanning microscopy (CLSM) in a canine model. MATERIALS AND METHODS: In vivo CLSM
      images of the epithelia were taken the day before and on days 28, 56 and 112
      following HSCT. Peripheral blood counts and chimerism were determined. RESULTS:
      An increase of DCs after HSCT was detected in each animal in both investigated
      tissue types. Highest DC numbers in the flew and the gingiva were detected on day
      28 and in the corneal epithelium on day 56 after HSCT, respectively. CONCLUSION:
      Changes of DCs in ocular and non-ocular mucous membranes can be monitored by CLSM
      in vivo. The DC frequency in the cornea and mucosa changes following HSCT. DC
      recovery is rapid and their numbers correlate with the development of chimerism
      of peripheral blood mononuclear cells.

PMID- 24292581
TI  - Human platelet antigen-3 genotype predicts platelet count in patients with HCV
      infection.
AB  - BACKGROUND/AIM: A low platelet count is one of the most sensitive tests for
      cirrhosis detection in patients with hepatitis C virus (HCV) infection. We
      evaluated whether the human platelet antigen (HPA) genotype could predict
      platelet count in HCV-positive patients. MATERIALS AND METHODS: We genotyped the
      HPA 1, 2, 3, 5 and 15 polymorphisms in consecutive patients with HCV infection.
      RESULTS: Out of the 56 patients enrolled, 56.1% had liver cirrhosis. The mean
      platelet count was significantly lower in those with HPA1aa genotype than in
      those with HPA1ab/bb genotype. Platelet count did not differ among the other HPA
      polymorphisms. However, at logistic regression analysis, only the HPA3aa genotype
      and liver cirrhosis were independent predictors of a low platelet count.
      CONCLUSION: HPA3aa is an independent factor for a low platelet count in this
      cohort of patients with HCV chronic infection regardless of disease stage.

PMID- 24292582
TI  - Extract of medicinal mushroom Agaricus blazei Murill enhances the non-specific
      and adaptive immune activities in BALB/c mice.
AB  - Agaricus blazei Murill (AbM) is traditionally used against a wide range of
      conditions such as ulcerative colitis, Crohn's disease, foot-and-mouth disease
      and chronic hepatitis C infection. In this study, we evaluated the
      immunomodulatory effects of AbM. For the non-specific immune response
      experiments, a total of 40 female BALB/c mice were divided into control (group 1)
      and experimental (groups 2-4) groups of 10 animals each. Groups 2, 3 and 4 were
      orally-administered high (819 mg/kg), medium (273 mg/kg) and low (136.5 mg/kg)
      doses of AbM daily for six weeks and then six parameters related to non-specific
      immune response were detected. For the adaptive immune response experiments, 40
      female mice were similarly divided into four groups. After six weeks of
      treatment, animals were immunized with the OVA immunogen. Two weeks later,
      splenocytes and sera were collected. Four parameters related to adaptive immune
      response were evaluated. We found that feeding mice with AbM extract increased
      the IgG level in serum, promoted phagocytosis of peritoneal macrophages and
      elevated the activity of Natural killer cells. We also found that the highest
      dose of AbM increased interleukin-2 (IL-2) levels in splenocytes and that a
      medium dose increased interferon-gamma. The levels of interleukin-4 (IL-4) were
      reduced or unchanged. T-helper type 1 cytokine levels were increased. AbM
      increased the humoral immune response and also affected the cellular immune
      response. These results provide evidence that AbM can modulate innate and
      adaptive immunity. 

PMID- 24292583
TI  - IL-17E production is elevated in the lungs of Balb/c mice in the later stages of
      Chlamydia muridarum infection and re-infection.
AB  - BACKGROUND: Pathogens can influence allergic respiratory diseases. We previously
      found that multiple infections with Chlamydophila pneumoniae induce the
      production of interleukin-17A (IL-17A) and IL-17E, which have roles in the
      pathogenesis of asthma. The present work was designed to investigate our
      hypothesis that infections with another pathogen can induce the production of IL
      17A and IL-17E. MATERIALS AND METHODS: At an internal of 28 days, mice were
      infected twice with Chlamydia muridarum; the kinetics of IL-17A and IL-17E
      expression was subsequently determined at the mRNA and protein levels. The
      amounts of IL-17 cytokines produced by the stimulated spleen cells were
      determined by enzyme-linked immunosorbent assay (ELISA). The presence of IL-17E
      in the lungs was revealed by an indirect immunofluorescence test. RESULTS: The
      infection with C. muridarum induced the production of IL-17A at the early stages
      of infection. The quantity of IL-17E was highest on days 28 and 56 after the
      first infection (28 days after the second infection). In the later stages of
      infection, IL-17E was produced by epithelial cells. The re-stimulated peripheral
      spleen cells produced IL-17A. CONCLUSION: Multiple infection with C. muridarum
      induces the production of a high amount of IL-17E, which plays an important part
      in the pathogenesis of allergic pulmonary diseases.

PMID- 24292584
TI  - Immunohistochemical characterization of N-methyl-N-nitrosourea-induced mammary
      tumours of Sprague-Dawley rats.
AB  - BACKGROUND: Single dose of N-methyl-N-nitrosourea (MNU) was shown to induce
      malignant tumours in susceptible rat strains. However, such tumours are not well
      characterized. MATERIAL AND METHODS: We characterized MNU-induced tumours in
      Sprague-Dawley rats using ultrasonographic, radiographic and immunohistochemical
      (IHC) methods. RESULTS: In 27 rats, 41 tumours developed, appearing
      ultrasonographically as hypodense, non-homogenic areas with signal enhancement at
      their periphery. Out of these, 39 were of malignant epithelial origin, with an
      IHC phenotype closely-resembling that of human invasive ductal breast carcinoma.
      One case was diagnosed as carcinosarcoma. IHC analysis revealed that Ki-67
      antigen expression correlated positively with tumour volume (r=0.40, p=0.0079).
      Moreover, tumours with alpha-smooth muscle actin in the tumour stroma were
      characterized by a higher proliferative rate as compared to those without its
      expression (p<0.05). CONCLUSION: This rat model of chemical carcinogenesis may be
      suitable for examining breast cancer development and progression.

PMID- 24292585
TI  - Ultrasonographic evaluation of gastrocnemius muscle in a rat model of N-methyl-N
      nitrosourea-induced mammary tumor.
AB  - BACKGROUND/AIM: Ultrasonography is frequently used to study body tissues. Our aim
      was to evaluate by ultrasonography, gastrocnemius muscle wasting induced by
      cancer in a rat model of chemically-induced mammary tumor, muscular response to
      exercise. MATERIALS AND METHODS: Female Sprague-Dawley rats were divided into as
      well as four groups. Groups I and II were injected with N-methyl-N-nitrosourea
      (MNU). Groups I and III performed endurance training on a treadmill.
      Gastrocnemius muscles were palpated for tonus evaluation. Gastrocnemius muscle
      and fibrous tissue between muscle and tibia were examined by ultrasonography. At
      necropsy, muscle was collected and weighed. Myostatin was assessed by
      immunoblotting. RESULTS: The final body weight, gastrocnemius weight, length and
      width were similar among groups. Tone of muscle was higher in exercised animals.
      Myostatin was higher in MNU-treated groups. Echogenicity of muscle and fibrous
      tissue in group IV was higher than in other groups (p<0.05). Echogenicity of
      fibrous tissue was higher than echogenicity of muscle in all groups. CONCLUSION:
      Our results showed that muscle ultrasonography is a useful tool to identify
      alterations in muscle structure. More studies are necessary for researchers to
      understand the influence of fat location in muscle ultrasonographic imaging.

PMID- 24292586
TI  - Alpha-phellandrene promotes immune responses in normal mice through enhancing
      macrophage phagocytosis and natural killer cell activities.
AB  - alpha-Phellandrene, a natural compound from natural plants, has been used in the
      food and perfume industry. We investigated the effects of alpha-phellandrene on
      the immune responses on normal murine cells in vivo. Normal BALB/c mice were
      treated orally with or without alpha-phellandrene at 0, 1, 5 and 25 mg/kg and
      olive oil as a positive control for two weeks. Results indicated that alpha
      phellandrene did not change the weight of animals when compared to olive oil
      (vehicle for alpha-phellandrene)-treated groups. After flow cytometric assay of
      blood samples it was shown that alpha-phellandrene increased the percentage of
      CD3 (T-cell marker), CD11b (monocytes) and MAC3 (macrophages), but reduced the
      percentage of CD19 (B-cell marker) cell surface markers in alpha-phellandrene
      treated groups, compared to untreated groups. alpha-Phellandrene promoted the
      phagocytosis of macrophages from blood samples at 5 and 25 mg/kg treatment and
      promoted natural killer cell activity from splenocytes at 25 mg/kg. Furthermore,
      alpha-phellandrene increased B-cell proliferation at 25 mg/kg with or without
      stimulation but promoted cell proliferation only at 25 mg/kg treatment with
      stimulation. Based on these observations, 25 mg/kg with alpha-phellandrene seems
      to have promoted immune responses in this murine model. 

PMID- 24292587
TI  - Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma
      and human prostate cancer cell lines in vitro.
AB  - BACKGROUND: Cancer cells become refractory to chemotherapy as a consequence of
      their overexpression of multidrug transporters. MATERIALS AND METHODS: The
      anticancer and multidrug resistance (MDR) reversal effects of the racemic form
      and the two enantiomers of thoridazine were investigated on a mouse T-lymphoma
      cell line over-expressing the ATP-binding cassette, subfamily-B (MDR/TAP), member
      1 (ABCB1) transporter (also known as P-glycoprotein) and on human PC3 prostate
      cancer cell line by 3-(4.5-dimethylthiazolyl-2)-2.5-diphenyl tetrazolium bromide
      (MTT) assay. The modulation of ABCB1 transporter activity was studied by
      rhodamine123 accumulation, the apoptosis-inducing effect was investigated using
      fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.
      RESULTS: The thioridazine racemic and (+) and (-) enantiomers were similarly
      effective. Drug accumulation by MDR mouse T-lymphoma cells was moderately
      modified in the presence of thioridazine derivatives. Thioridazine induced
      apoptosis of the MDR cancer cell line, but there was no significant apoptotic
      effect on the PC3 cell line. CONCLUSION: Apparently, the chirality of
      thioridazine has no importance in the inhibition of MDR phenotype of cancer
      cells.

PMID- 24292588
TI  - PET-positive polyostotic fibrous dysplasia mimicking Ollier disease.
AB  - Fibrous dysplasia can be monostotic or, less commonly, polyostotic. The imaging
      features of polyostotic fibrous dysplasia may closely mimic those of metastatic
      bone disease, Paget disease, or enchondromatosis (Ollier disease). We present a
      unique case of polyostotic fibrous dysplasia in a 57-year-old female with a
      medical history of enchondromas involving the proximal phalanges of the left
      hand. The skeletal radiographs showed unilateral multiple bone lesions suggestive
      of polyostotic fibrous dysplasia. On magnetic resonance imaging, the lesions
      exhibited low-to-intermediate signal intensity on T1-weighted images and
      heterogeneous high signal intensity on T2-weighted images. Contrast-enhanced fat
      suppressed T1-weighted images demonstrated moderate heterogenous enhancement.
      Integrated positron-emission tomography (PET)/computed tomography scan
      demonstrated increased (18)F-fluorodeoxyglucose (FDG) uptake within several
      bones, including the humerus, ilium, femur, and fibula, all on the left side. The
      maximal standardized uptake value of these lesions ranged from 2.18 to 3.78. We
      performed an open biopsy of the left humerus and histological examination
      confirmed the diagnosis of fibrous dysplasia. To the best of our knowledge, this
      is the first case of biopsy-proven FDG PET-positive polyostotic fibrous dysplasia
      with enchondromas of the hand. 

PMID- 24292589
TI  - The integrated role of ultrasonography in the diagnosis of soft tissue metastases
      from melanoma: preliminary report of a single-center experience and literature
      review.
AB  - Currently melanoma has the fastest growing incidence of all cancers in men and
      the second in women (after lung cancer) in Western countries. Since prognosis of
      skin melanoma is excellent in early stages but dramatically worsens in advanced
      stages, an early diagnosis is fundamental in granting patients a favorable
      outcome. Sentinel node (SN) biopsy represents the gold standard for accurately
      staging melanoma, but other tests are commonly endorsed both in the initial
      staging work-up and in the follow-up, such as ultrasonography, computed
      tomography (CT)-scan and positron emission tomography (PET)-CT. PET-CT, among
      others, has high sensitivity and specificity for the study of distant metastases,
      the assessment of soft tissues and lymph node involvement, and for the guidance
      of surgical biopsies. Ultrasonography (US) is a non-invasive procedure whose use
      has recently expanded in our service, both preoperatively, intraoperatively and
      postoperatively, thanks to its wide availability, low costs and easy and fast
      reproducibility; ultrasonography even surpassed the reliability of PET-CT or CT
      scan in the seven cases presented herein. US is operator-dependent, and this is
      probably the major limitation of the procedure, together with lack of prospective
      studies validating its strength, but our preliminary study demonstrates that
      ultrasound can assume an important role in melanoma, both for staging and the
      follow-up of patients, especially with lymph nodal or subcutaneous involvement. 

PMID- 24292590
TI  - Submaximal spiroergometric parameters are unaffected by severity of chronic
      obstructive pulmonary diseases.
AB  - BACKGROUND/AIM: The Global initiative for chronic obstructive lung diseases
      (GOLD) reports a staging system for chronic obstructive pulmonary disease (COPD)
      based on airflow limitations at rest. Cardiopulmonary exercise testing (CPET) is
      used in surveys to determine the remaining working capacity concerning the degree
      of disability and the disability benefit payment after rehabilitation in patients
      with COPD. The aim of the present study was to examine if sub-maximal exercise
      levels also correlate with COPD disease stage. PATIENTS AND METHODS: A total of
      63 consecutive male patients with COPD and 24 elderly healthy volunteers
      underwent pulmonary functional tests including CPET. Work capacity, oxygen
      uptake, ventilation volume, carbon dioxide production and arterial blood gases
      were measured. RESULTS: Exercise capacity, oxygen uptake, ventilation volume,
      oxygen pulse, carbon dioxide output and arterial oxygen pressure decreased
      significantly (p<0.001) with advancing GOLD stage. Significant positive
      correlations (p<0.001) to GOLD stage were seen for the alveolar-arterial
      differences for oxygen pressure and arterial carbon dioxide pressure. Weight
      related exercise capacity (p<0.001), oxygen uptake (p<0.01) and lactate
      concentrations (p<0.05) were significantly lower in patients with COPD. Reduction
      of (weight-related) oxygen uptake, ventilation volume, oxygen pulse or carbon
      dioxide output at identical sub-maximal workload was not detected according to
      GOLD stage, not in comparison of patients with healthy individuals. CONCLUSION:
      The GOLD staging system correlates with maximal CPET. At identical workload,
      discrimination between patients with different GOLD stages and healthy
      individuals was not possible. For the detection of exercise impairment, maximal
      CPET is recommended.

PMID- 24292592
TI  - Bioelectrical impedance analysis in pregnancy: reference ranges.
AB  - AIM: To generate reference values for bioelectrical impedance analysis (BIA) in a
      German collective of healthy pregnant women. MATERIALS AND METHODS: A total of 90
      women with a singleton gestation from 23+0 to 40+6 weeks of pregnancy were
      enrolled from April 2012 until May 2013. Each week of gestation was represented
      by the same number of women (n=5). Mean BIA indices were generated for all
      patients and according to gestational age so that three collectives <30, 30 to 35
      and >35 weeks of gestation were formed. Multiple regression analysis was
      implemented using maternal height, weight, body-mass index, gestational age,
      hematocrit and abdominal circumference to generate formulae to calculate
      individualized reference values for resistance, reactance, phase angle,
      height(2)/resistance, and total body water adjusted for gestation. RESULTS:
      Individualised reference values using the new formulae led to results which are
      more accurate than general mean values or mean values corresponding to the
      gestational age only. CONCLUSION: As far as we are aware of the present study is
      the first to report reference values for BIA indices in a German collective of
      healthy pregnant women. The new formulae generated by multiple regression
      analysis enabled for assessment of individualized reference values for BIA
      indices.

PMID- 24292591
TI  - Prevalence of HHV-6 and HHV-8 antibodies in patients with autism spectrum
      disorders.
AB  - BACKGROUND/AIM: The etiology of autism spectrum disorders (ASD) still eludes
      investigators. Several viral infections have been associated with ASD
      etiopathogenesis but few studies have ever focused on the role of HHV-6 and HHV
      8, two members of the herpesviridae family. The aim of the present study was to
      evaluate seropositivity rate and levels of antibodies to HHV6 and HHV-8 in
      children with ASD compared to controls. PATIENTS AND METHODS: We measured and
      compared seropositivity rate and levels of antibodies to HHV-6 and HHV-8 in 30
      children with ASD (14 with autistic disorder and 16 with non-autistic disorder
      ASD) and in 28 healthy controls of the same age. RESULTS: Seropositivity rate and
      levels of the two antibodies were similar in cases and controls. Seropositivity
      rate and levels of antibodies were not correlated with disease severity in
      children with ASD. CONCLUSION: Levels and seropositivity rate of antibodies to
      HHV-6 and HHV-8 do not differ between children with ASD and controls.

PMID- 24292593
TI  - Financial viability of perinatal centers in the longer term, taking legislative
      requirements into account. An examination of the cost-revenue structure of a
      Level I perinatal center.
AB  - BACKGROUND: Debate is currently taking place over minimum case numbers for the
      care of premature infants and neonates in Germany. As a result of the Federal
      Joint Committee (Gemeinsamer Bundesauschuss, G-BA) guidelines for the quality of
      structures, processes, and results, requiring high levels of staffing resources,
      Level I perinatal centers are increasingly becoming the focus for health
      economics questions, specifically, debating whether Level I structures are
      financially viable. MATERIALS AND METHODS: Using a multistep contribution margin
      analysis, the operating results for the Obstetrics Section at the University
      Perinatal Center of Franconia (Universitats-Perinatalzentrum Franken) were
      calculated for the year 2009. Costs arising per diagnosis-related group (DRG)
      (separated into variable costs and fixed costs) and the corresponding revenue
      generated were compared for 4,194 in-patients and neonates, as well as for 3,126
      patients in the outpatient ultrasound and pregnancy clinics. RESULTS: With a
      positive operating result of ? 374,874.81, a Level I perinatal center on the
      whole initially appears to be financially viable, from the obstetrics point of
      view (excluding neonatology), with a high bed occupancy rate and a profitable
      case mix. By contrast, the costs of prenatal diagnostics, with a negative
      contribution margin II of ? 50,313, cannot be covered. A total of 79.4% of DRG
      case numbers were distributed to five DRGs, all of which were associated with
      pregnancies and neonates with the lowest risk profiles. CONCLUSION: A Level I
      perinatal center is currently capable of covering its costs. However, the cost
      revenue ratio is fragile due to the high requirements for staffing resources and
      numerous economic, social, and regional influencing factors.

PMID- 24292594
TI  - Complementary medicine on side-effects of adjuvant hormone therapy in patients
      with breast cancer.
AB  - BACKGROUND: This clinical investigation was performed in order to evaluate the
      benefit of complementary medicine in patients with breast cancer undergoing
      adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=680) were
      treated according to international guidelines. All patients suffered from
      arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce
      side-effects, the patients were complementarily treated with a combination of
      sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens
      culinaris lectin. On case report formulas, self assessment of defined side
      effects of HT (namely arthralgia and mucosal dryness) were documented before and
      four weeks after complementary treatment. Validation was carried out by scoring
      from 1 (no side-effects/optimal tolerability) to 6 (extreme side
      effects/extremely poor tolerability), however, only patients suffering from
      severe side-effects (symptom scores >3) were enrolled in this investigation.
      RESULTS: A total of 64% (316 out of 494) of patients suffering from severe
      arthralgia and 62% of patients (194 out of 310) with severe mucosal dryness
      significantly benefited from complementary medicine. The severity of side-effects
      of HT was reduced by complementary treatment. Mean scores of symptoms declined
      from 4.92 before treatment to 3.16 after four weeks of treatment for arthralgia
      and from 4.83 before treatment to 3.21 after four weeks of treatment for mucosal
      dryness, and these were the primary aims of this investigation. The reduction of
      side-effects of HT was statistically significant (p<0.001) after four weeks.
      CONCLUSION: This investigation further demonstrates benefits of indication-based
      complementary treatment with the combination of sodium selenite, proteolytic
      enzymes and L. culinaris lectin in patients with breast cancer.

PMID- 24292595
TI  - Methicillin-resistant Staphylococcus aureus infection rate after implementation
      of an antibiotic care bundle based on results of rapid molecular screening.
AB  - AIM: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a
      risk factor for subsequent invasive MRSA infection, particularly in patients
      admitted to critical areas. We conducted a surveillance among patients admitted
      to our Intensive Care Unit (ICU) to determine whether the implementation of a
      specific MRSA antibiotic care bundle (ACB) based on rapid molecular screening for
      MRSA and de-colonization, reduced the total MRSA infection rate. MATERIALS AND
      METHODS: A total of 431 and 577 nasal swabs were obtained from ICU patients at
      admission from April 2009 through December 2010 (pre-ACB period) and, after the
      bundle implementation, from January 2011 through December 2012 (post-ACB period),
      respectively. Nasal swabs were analyzed by the rapid molecular test Xpert MRSA.
      All patients were followed-up during their whole ICU stay to determine whether
      they developed MRSA infection. RESULTS: Overall, 31 out of 431 (7.1%) patients
      were colonized with MRSA at admission during the pre-ACB period and 49 out of 577
      (8.4%) were colonized with MRSA during the post-ACB period. The rate of MRSA
      infection in ICU significantly declined from 2% in pre-ACB to 0.3% in post-ACB,
      with a total decrease of 100% in two consecutive semesters between July 2011 and
      July 2012 (p<0.001). CONCLUSION: The analysis demonstrated a significant decline
      in MRSA infections following the introduction of active rapid molecular
      surveillance and the specific ACB at our ICU and in the risk associated with MRSA
      bacteremia.

PMID- 24292596
TI  - Association between AMH, oocyte number and availability of embryos for
      cryopreservation in IVF.
AB  - AIM: To investigate possible associations between serum anti-Mullerian hormone
      (AMH) levels, the number of oocytes collected and the availability and
      suitability of produced embryos for cryopreservation in in-vitro fertilization
      (IVF) cycles. PATIENTS AND METHODS: Sixty women in their first
      IVF/intracytoplasmic sperm injection (ICSI) cycle were studied. The short
      stimulation protocol was used for controlled ovarian hyperstimulation. AMH levels
      were measured during the menstrual cycle preceding treatment. RESULTS: A strong,
      positive correlation between AMH and the number of collected oocytes was found.
      The patients with available and suitable embryos for cryopreservation had
      significantly higher levels of AMH. CONCLUSION: AMH appears to be a valuable
      marker mainly for ovarian reserve and response to IVF treatment. AMH levels are
      strongly associated with the number of retrieved oocytes and the availability of
      supernumerary embryos suitable for cryopreservation.

PMID- 24292598
TI  - Effect of whole-body vibration and insulin-like growth factor-I on muscle
      paralysis-induced bone degeneration after botulinum toxin injection in mice.
AB  - Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone
      degradation with substantial bone loss. We hypothesized that whole-body vibration
      (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis
      induced bone degradation following BTX injections by activation of the protein
      kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were
      assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I,
      BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the
      study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right
      hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous
      injections of human IGF-I (1 MUg/day). The BTX+WBV and BTX+WBV+IGF-I groups
      underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks.
      Femora were scanned by pQCT, and mechanical properties were determined. On tibial
      sections TRAP staining, static histomorphometry, and immunohistochemical staining
      against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were
      conducted. BTX injection decreased trabecular and cortical bone mineral density.
      The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral
      density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings
      were not differentially altered in the injected hind limbs between groups. We
      found that high-frequency, low-magnitude WBV can counteract paralysis-induced
      bone loss following BTX injections, while we could not detect any effect of
      treatment with IGF-I.

PMID- 24292599
TI  - Endohedral metal or a fullerene cage based oxidation? Redox duality of nitride
      clusterfullerenes Ce(x)M(3-x)N@C(78-88) (x = 1, 2; M = Sc and Y) dictated by the
      encaged metals and the carbon cage size.
AB  - Redox behavior of endohedral metallofullerenes, in particular their oxidation
      process, can be classified as a fullerene-based or endohedral species-based
      process according to the mechanism of the electron transfer. Here we report on
      the phenomenon of the strain-driven electrochemical behavior achieved by
      encapsulating the cerium-containing clusters into a series of carbon cages
      ranging from C78 to C88. The Ce-based mixed metal nitride clusterfullerenes CexM3
      xN@C2n (x = 1, 2; M = Sc or Y; 2n = 78-88) were synthesized and characterized.
      The magnitude of the inherent strain caused by the limited inner space of the
      carbon cage for the relatively large nitride clusters can be varied by choosing
      different scaffold metals (Sc, Lu, or Y) to tailor the size of the encaged CexM3
      xN cluster and by matching the nitride cluster with different fullerene cages in
      the size range from C78 to C88. The redox properties of CexM3-xN@C2n were
      investigated by cyclic and square wave voltammetry. The mechanism of the
      electrochemical oxidation of Ce-based mixed metal nitride clusterfullerenes, in
      particular whether the fullerene-based oxidation or the Ce(III) -> Ce(IV) process
      is observed, is found to be dependent on the scaffold metal and the size of the
      fullerene cage. The endohedral oxidation of Ce(III) to Ce(IV) was observed for a
      number of compounds as revealed by the negative shift of their oxidation
      potentials with respect to the values measured for the non-Ce analogues.
      Experimental studies are supported by DFT calculations. We conclude that the
      prerequisites for the Ce-based endohedral oxidation process are suitable inherent
      cluster-cage strain and sufficiently high oxidation potential of the fullerene
      cage. 

PMID- 24292600
TI  - Two-stage operation for thoracic esophageal cancer: esophagectomy and subsequent
      reconstruction by a free jejunal flap.
AB  - When the stomach is unavailable for esophageal reconstruction due to previous
      gastrectomy or synchronous gastric cancer, a pedicled jejunum or colon, with or
      without vascular supercharge, has been the alternative. However, these
      reconstructions are not free from severe complications, such as necrosis. We have
      introduced a new surgical technique for delayed esophageal reconstruction using a
      free jejunal flap. We used this technique in 11 patients. Four weeks after
      subtotal esophagectomy, reconstruction using free jejunal flaps was performed. A
      free jejunum was placed at the pre-sternum, and the internal thoracic artery and
      vein were usually used as the recipient vessels. There were no cases of flap
      necrosis and no hospital deaths. Anastomotic leakage occurred in two cases. Both
      leakages were cured by conservative treatment. Delayed esophageal reconstruction
      using a free jejunal flap can be considered to be a safe procedure when the
      stomach is unavailable as an esophageal substitute.

PMID- 24292601
TI  - Anti-Mullerian hormone: determination of ovarian reserve in early breast cancer
      patients.
AB  - Breast cancer is the most common invasive cancer in women of reproductive age. In
      young women, chemotherapy may induce amenorrhea: it is still uncertain how to
      assess menopausal status in these patients despite the importance of its
      definition for choosing appropriate endocrine treatment. In the development of
      sensitive biomarkers for fertility and ovarian reserve, anti-Mullerian hormone
      (AMH) is considered a promising marker of ovarian reserve. The clearest data
      regarding a clinical use of AMH are related to the measurement of the ovarian
      pool in women who undergo IVF: the available data, also in breast cancer
      patients, seem to suggest that AMH measurement, before gonadotropin
      administration, can be a useful marker for the prediction of women at risk for
      poor-response or no response to ovarian stimulation. The utility of AMH as a
      potential marker of chemotherapy-induced ovarian follicular depletion and an
      early plasma marker of chemotherapy-induced gonadal damage has been evaluated
      both in young women after treatment for cancer in childhood and in young
      survivors of hematological malignancies and solid tumors. Several studies have
      demonstrated a potential utility of AMH, inhibin, or follicle-stimulating factor
      as biomarkers predicting infertility risk in breast cancer patients, but the
      studies conducted so far are not conclusive. Further studies are needed in order
      to define the regimen-specific action of chemotherapy on AMH levels, the
      percentage of post-treatment recovery of plasma levels of the hormone, and the
      relationship between menopausal status and AMH. 

PMID- 24292602
TI  - Zebrafish as an innovative model for neuroendocrine tumors.
AB  - Tumor models have a relevant role in furthering our understanding of the biology
      of malignant disease and in preclinical cancer research. Only few models are
      available for neuroendocrine tumors (NETs), probably due to the rarity and
      heterogeneity of this group of neoplasms. This review provides insights into the
      current state-of-the-art of zebrafish as a model in cancer research, focusing on
      potential applications in NETs. Zebrafish has a complex circulatory system
      similar to that of mammals. A novel angiogenesis assay based on the injection of
      human NET cell lines (TT and DMS79 cells) into the subperidermal space of the
      zebrafish embryos has been developed. Proangiogenic factors locally released by
      the tumor graft affect the normal developmental pattern of the subintestinal
      vessels by stimulating the migration and growth of sprouting vessels toward the
      implant. In addition, a description of the striking homology between zebrafish
      and humans of molecular targets involved in tumor angiogenesis (somatostatin
      receptors, dopamine receptors, mammalian target of rapamycin), and currently used
      as targeted therapy of NETs, is reported. 

PMID- 24292603
TI  - The histone methyltransferase EZH2, an oncogene common to benign and malignant
      parathyroid tumors.
AB  - Primary hyperparathyroidism (pHPT) resulting from parathyroid tumors is a common
      endocrine disorder with incompletely understood etiology. In renal failure,
      secondary hyperparathyroidism (sHPT) occurs with multiple tumor development as a
      result of calcium and vitamin D regulatory disturbance. The aim of this study was
      to investigate a potential role of the histone 3 lysine 27 methyltransferase EZH2
      in parathyroid tumorigenesis. Parathyroid tumors from patients with pHPT included
      adenomas and carcinomas. Hyperplastic parathyroid glands from patients with HPT
      secondary to uremia and normal parathyroid tissue specimens were included in this
      study. Quantitative RT-PCR, western blotting, bisulfite pyrosequencing, colony
      formation assay, and RNA interference were used. EZH2 was overexpressed in a
      subset of the benign and in all malignant parathyroid tumors as determined by
      quantitative RT-PCR and western blotting analyses. Overexpression was explained
      by EZH2 gene amplification in a large fraction of tumors. EZH2 depletion by RNA
      interference inhibited sHPT-1 parathyroid cell line proliferation as determined
      by tritium-thymidine incorporation and colony formation assays. EZH2 depletion
      also interfered with the Wnt/beta-catenin signaling pathway by increased
      expression of growth-suppressive AXIN2, a negative regulator of beta-catenin
      stability. Indeed, EZH2 contributed to the total level of aberrantly accumulated
      transcriptionally active (nonphosphoylated) beta-catenin in the parathyroid tumor
      cells. To our knowledge EZH2 gene amplification presents the first genetic
      aberration common to parathyroid adenomas, secondary hyperplastic parathyroid
      glands, and parathyroid carcinomas. This supports the possibility of a common
      pathway in parathyroid tumor development. 

PMID- 24292604
TI  - Association of water extract of green propolis and liposomal meglumine
      antimoniate in the treatment of experimental visceral leishmaniasis.
AB  - This work investigated the use of water extract of green propolis (WEP) and its
      association with free or liposomal meglumine antimoniate (MA) for the treatment
      of murine visceral leishmaniasis. Mice infected with Leishmania infantum were
      treated with oral doses of WEP associated or not with a single dose of liposomal
      MA by intraperitoneal route. Parasite burden was assessed in the liver and spleen
      by limiting dilution assay, and alterations in the spleen cellular phenotype were
      evaluated by flow cytometry. Tissue damage was assessed by determination of
      biochemical markers of the liver, heart, and kidney function and
      histopathological analysis of the liver and spleen. Our data showed that
      treatment with WEP was able to reduce parasite load in the liver but not in the
      spleen. On the other hand, liposomal MA reduced parasite load in both organs.
      Unexpectedly, there was no synergism with the combination of WEP and liposomal MA
      in reducing the parasite load. The histopathological analysis showed that
      administration of WEP, liposomal MA, or their association was able to protect the
      liver and spleen from lesions caused by infection. No alteration in the profile
      of spleen cells by flow cytometry or in the liver, heart, and kidney functions by
      biochemical markers due to any of the treatments was observed. These results
      demonstrate that although WEP was able to significantly reduce the liver parasite
      load, its association with liposomal MA did not lead to significant improvement
      in reducing parasite load. On the other hand, treatment with WEP and/or liposomal
      MA protected the liver and spleen from lesions caused by the infection. 

PMID- 24292605
TI  - Single- or mixed-sex Schistosoma japonicum infections of intermediate host snails
      in hilly areas of Anhui, China.
AB  - Schistosomiasis japonicum is one of the most serious communicable diseases, and
      the transmission of the parasite is dependent of its complex life cycle on which
      many factors can have an impact. Multiple infections comprising both male and
      female schistosome within snail intermediate hosts, for example, would facilitate
      parasite transmission. However, no research on Schistosoma japonicum communities
      in field-collected Oncomelania hupensis hupensis in relation to schistosome sex
      has been reported. Therefore, snail survey was performed in a hilly region of
      Anhui, China, and single- or mixed-sex schistosome infections of snails were
      detected with final host mouse infection. A total of 8,563 snails were sampled in
      the field, and 67 were identified with schistosome infections. Of these infected
      snails, 46 were selected for final host infection. From this, 21 snails were
      infected with female schistosome, 23 with males and 2 with both males and
      females. More worms were recovered for snails with mixed-sex infections than with
      single-sex infection and for snails with male schistosome infection than with
      female infection (P<0.001). The observed frequency of mixed-sex infections of
      snails was significantly higher than would be expected if randomly distributed
      (P<0.01). The ratio male/female of schistosome infections in snails was nearly
      equal and up to 95.65 % (44/46) of infected snails were single-sex infection.
      Schistosome infections in snails collected from the hilly area of Anhui Province
      were not randomly distributed but over-dispersed.

PMID- 24292606
TI  - Endovascular embolization of cerebral arteriovenous malformations: results of the
      Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2.
AB  - This retrospective study constitutes a part of the Japanese Registry of
      Neuroendovascular Therapy (JR-NET) 1 and 2. Its purpose is to evaluate the
      feasibility, safety, and outcome of endovascular embolization for cerebral
      arteriovenous malformations (AVMs) in Japan. Nine hundred and eighty-seven
      embolization procedures were registered with JR-NET 1 and 2 (424 procedures in
      122 institutions with JRNET 1 and 563 procedures in 150 institutions with JRNET
      2). In total, 790 patients (80.1%) had favourable clinical outcomes defined as
      modified Rankin Scale (mRS) scores 0-2 at 30 days after embolization. Complete
      AVM obliteration by embolization alone was achieved in 90 procedures (9.1%). The
      procedural morbidity and mortality rate was 2.5% and 0.3% per procedure,
      respectively. In the multivariate logistic regression models, deep venous
      drainage and embolization of four or more feeding pedicles per session were
      significantly associated with any treatment-related complications (P = 0.02 and P
      = 0.003, respectively). About 6 cm or more in maximum nidus diameter had a
      negative correlation with complications (P = 0.003). Our study shows that
      embolization of cerebral AVMs was performed with a high degree of safety and a
      low rate of symptomatic complications in Japan. 

PMID- 24292607
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- 24292608
TI  - Endovascular treatment of acute stroke with major vessel occlusion before
      approval of mechanical thrombectomy devices in Japan: Japanese Registry of
      Neuroendovascular Therapy (JR-NET) and JR-NET 2.
AB  - The aim of this study was to clarify the general status and historical transition
      of endovascular therapy (EVT) of acute stroke with major vessel occlusion before
      approval of mechanical thrombectomy devices in Japan from January 2005 to
      December 2009. We extracted 1,409 acute ischemic stroke patients receiving EVT
      (513 women, 69.8 +/- 11.8 years) from two nationwide registry studies, the
      Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2. The median
      baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and
      81.3% of the patients received EVT within 6 hours after symptom onset. The
      culprit occluded arteries were the internal carotid artery (ICA) in 21.2%, middle
      cerebral artery (MCA) in 53.0%, and basilar artery (BA) in 20.6%. Intravenous
      thrombolysis was administered to 6.7% of the patients, and EVT mainly consisted
      of intra-arterial thrombolysis and percutaneous balloon angioplasty/balloon clot
      disruption. The final recanalization rate was 82.5%, and the clinical outcome was
      favorable in 35.8% and fatal in 11.6% at 30 days after onset or at discharge.
      There was no significant change in neurological severity at baseline throughout
      the study period, but the onset-to-treatment time became longer and the
      proportion of ICA or BA occlusion increased annually. Although the final
      recanalization rate was similar throughout the study period, the incidence of a
      favorable outcome tended to decreased annually from 41.0% to 29.0%. These results
      could be considered as baseline data that can be used to validate the beneficial
      effects of novel EVT devices in Japan. 

PMID- 24292609
TI  - Gymnastics participation is associated with skeletal benefits in the distal
      forearm: a 6-month study using peripheral Quantitative Computed Tomography.
AB  - OBJECTIVES: Musculoskeletal development of the upper limbs during exposure to
      weight-bearing loading is under-researched during early pubescent growth. The
      purpose was to assess the changes in upper body musculoskeletal strength in young
      girls following 6 months of non-elite gymnastics participation. METHODS: Eighty
      four girls, 6-12 years were divided into groups based on gymnastics
      participation: high-training (HGYM, 6-16 hr/wk), low-training (LGYM, 1-5 hr/wk),
      and non-gymnasts (NONGYM). Volumetric BMD, bone geometry, estimated bone strength
      and muscle size were assessed at the non-dominant forearm (4% and 66% radius and
      ulna) with pQCT. DXA assessed aBMD and body composition. Tests for explosive
      power, muscle strength, and endurance were also performed. RESULTS: Interaction
      effects were observed in all variables at the 4% radius. At the 66% ulna, HGYM
      and LGYM had greater bone mass, size and bone strength than NONGYM, furthermore a
      dose-response relationship was observed at this location. Body composition was
      better for HGYM than LGYM and NONGYM, however muscle function was better for HGYM
      and LGYM than NONGYM. CONCLUSION: The greatest changes were obtained with more
      than one gymnastics class per week. Separating gymnastics participation-related
      changes from those associated with normal growth and development remains
      difficult, particularly at the 4% radius.

PMID- 24292610
TI  - Spaceflight and hind limb unloading induce similar changes in electrical
      impedance characteristics of mouse gastrocnemius muscle.
AB  - OBJECTIVE: To assess the potential of electrical impedance myography (EIM) to
      serve as a marker of muscle fiber atrophy and secondarily as an indicator of bone
      deterioration by assessing the effects of spaceflight or hind limb unloading.
      METHODS: In the first experiment, 6 mice were flown aboard the space shuttle (STS
      135) for 13 days and 8 earthbound mice served as controls. In the second
      experiment, 14 mice underwent hind limb unloading (HLU) for 13 days; 13
      additional mice served as controls. EIM measurements were made on ex vivo
      gastrocnemius muscle. Quantitative microscopy and areal bone mineral density
      (aBMD) measurements of the hindlimb were also performed. RESULTS: Reductions in
      the multifrequency phase-slope parameter were observed for both the space flight
      and HLU cohorts compared to their respective controls. For ground control and
      spaceflight groups, the values were 24.7+/-1.3 degrees /MHz and 14.1+/-1.6
      degrees /MHz, respectively (p=0.0013); for control and HLU groups, the values
      were 23.9+/-1.6 degrees /MHz and 19.0+/-1.0 degrees /MHz, respectively (p=0.014).
      This parameter also correlated with muscle fiber size (rho=0.65, p=0.011) for
      spaceflight and hind limb aBMD (rho=0.65, p=0.0063) for both groups. CONCLUSIONS:
      These data support the concept that EIM may serve as a useful tool for assessment
      of muscle disuse secondary to immobilization or microgravity.

PMID- 24292611
TI  - Vibration platform for mice to deliver precise, low intensity mechanical signals
      to the musculoskeleton.
AB  - OBJECTIVE: Low intensity vibration as a therapeutic and training modality has
      received increased attention despite the lack of clear mechanistic pathways.
      Thus, to determine mechanisms underpinning vibration-induced musculoskeletal
      adaptations, a vibration platform for mice was designed, constructed, and
      validated. METHODS: Critical aspects of the platform include use of off-the-shelf
      components to (1) tailor individual parameter selection (acceleration and
      frequency), (2) produce low error across the plate's surface and throughout the
      range of vibration parameters, and (3) utilize accelerometer feedback to ensure
      fidelity within and between bouts of vibration. The vibration device is
      controlled by a centrally-mounted linear actuator on the underside of the
      platform that is modulated by accelerometer feedback. RESULTS: Triaxial
      accelerometers confirmed that vibrations were purely vertical and acceleration
      responses were within 5% of target stimuli for all accelerations (0.2-1.0 g) and
      frequencies (25-90 Hz). The platform produced acceleration responses with <=4%
      error between 25-90 Hz. Vibration modes were not detected indicating that the
      circular plate produced uniform stimuli across the platform (error <=1.1%,
      P>=0.23) and mouse body mass did not affect the platform's performance (P>=0.43).
      CONCLUSIONS: Our vibration device for mice improves upon existing devices and
      enables precise, low intensity mechanical signals to be applied with confidence.

PMID- 24292612
TI  - Musculoskeletal response of dystrophic mice to short term, low intensity, high
      frequency vibration.
AB  - OBJECTIVES: We aimed to identify parameters of low-intensity vibration that
      initiate the greatest osteogenic response in dystrophin-deficient mice and
      determine vibration safety for diseased muscle in three separate studies.
      METHODS: Study1: Mdx mice were randomized into seven vibration treatments and 14
      d later, plasma osteocalcin and tibial osteogenic gene expression were compared
      among treatments. Study2: Three days of vibration was compared to other
      modalities known to elicit muscle injury in mdx mice. Study3: Dystrophic mice
      with more severe phenotypes due to altered utrophin were subjected to 7 d
      vibration to determine if muscle injury was induced. Muscle torque and genes
      associated with inflammation and myogenesis were assessed in Studies 2-3.
      RESULTS: Two sets of parameters (45 Hz 0.6 g and 90 Hz 0.6 g) evoked osteogenic
      responses. 45 Hz upregulated alkaline phosphatase and tended to upregulate
      osteoprotegerin without altering RANKL, and 90 Hz simultaneously upregulated
      osteprotegerin and RANKL. Thus, subsequent muscle studies utilized 45 Hz.
      Vibration for 3 or 7 d was not injurious to dystrophic muscle as shown by the
      lack of differences between vibrated and non-vibrated mice in torque and gene
      expression. CONCLUSIONS: Results indicate that vibration at 45 Hz and 0.6 g is
      safe for dystrophic muscle and may be a therapeutic modality to improve
      musculoskeletal health in DMD.

PMID- 24292613
TI  - Long-term effects of whole-body vibration on motor unit contractile function and
      myosin heavy chain composition in the rat medial gastrocnemius.
AB  - Structural and physiological mechanisms underling functional adaptations of a
      muscle to chronic whole-body vibration (WBV) are poorly understood. The study
      aimed at examining the contractile properties of motor units and the myosin heavy
      chain (MHC) expression in rat medial gastrocnemius muscle in response to 3- or 6
      month periods of the WBV. The three-month WBV induced modifications of
      contractile properties principally in slow (S) and fast resistant to fatigue (FR)
      motor units. In S units an increase in the maximum tetanus force, a reduction in
      the twitch force and a decrease in the twitch-to-tetanus force ratio were found.
      In FR units a shortening in the twitch time parameters, a decrease in the twitch
      to-tetanus ratio and an increase in the fatigue resistance were observed. In
      addition, a decrease in the type I and an increase in the type IIax MHC content
      were revealed. The six-month WBV caused a decrease in the twitch-to-tetanus force
      ratio in S and FR units. Other structural and physiological changes in MU
      properties previously seen were no longer apparent. In conclusion, responses to
      the long-term WBV stimulus vary between particular types of motor units, what
      suggests that multiple adaptive processes in muscle tissue are involved. 

PMID- 24292614
TI  - Effects of vibration on flexibility: a meta-analysis.
AB  - Exogenous stimulation of skeletal muscle or tendon is often used to improve range
      of motion. Despite substantial research efforts, however, the effects of
      vibration on flexibility have not been clarified. In this review, we investigated
      the effects of acute and chronic intervention programs which used vibration to
      improve flexibility in young healthy individuals. Effect size was calculated
      using data from a total of 600 participants in 19 studies before and after the
      introduction of vibration-based intervention, and a total of 324 participants in
      13 studies on the additive effects of vibration compared with the identical
      conditions without vibration. Sub-group analyses were performed based on
      intervention period, type of exercise, and type of vibration. Meta-analysis
      showed that vibration interventions had significant effects on flexibility
      (standardized mean difference [SMD]=-0.79, 95% confidence interval [CI]=-1.14- 
      0.43; p<0.001), albeit with the possibility of heterogeneity (I(2)=75%). Another
      meta-analysis revealed a significant additive effect of vibration on flexibility
      compared with the identical condition without vibration (SMD=0.25, 95%CI=0.03
      0.48; P=0.03), with small heterogeneity (I(2)=0%). The risk of publication bias
      was low judged from Kendall's tau statistic. We concluded that the use of
      vibration might lead to additive improvements in flexibility. 

PMID- 24292615
TI  - Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's
      disease patients: a retrospective cohort study.
AB  - OBJECTIVES: This study was designed to assess effects of cholinergic stimulation
      using acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate
      cholinergic receptors and are used to treat Alzheimer's disease (AD), on healing
      of hip fractures. METHODS: A retrospective cohort study was performed using 46
      female AD patients, aged above 75 years, who sustained hip fractures. Study
      analyses included the first 6-months after hip fracture fixation procedure.
      Presence of AChEIs was used as predictor variable. Other variables that could
      affect study outcomes: age, body mass index (BMI), mental state or type of hip
      fracture, were also included. Radiographic union at fracture site (Hammer index),
      bone quality (Singh index) and fracture healing complications were recorded as
      study outcomes. The collected data was analyzed by student's-t, Mann-Whitney-U
      and chi-square tests. RESULTS: No significant differences in age, BMI, mental
      state or type of hip fracture were observed between AChEIs-users and nonusers.
      However, AChEIs-users had better radiographic union at the fracture site
      (relative risk (RR),2.7; 95%confidence interval (CI),0.9-7.8), better bone
      quality (RR,2.0; 95%CI,1.2-3.3) and fewer healing complications (RR,0.8;
      95%CI,0.7-1.0) than nonusers. CONCLUSION: In elderly female patients with AD, the
      use of AChEIs might be associated with an enhanced fracture healing and minimized
      complications.

PMID- 24292616
TI  - Vitamin D status and bone health in immigrant versus Swedish women during
      pregnancy and the post-partum period.
AB  - OBJECTIVE: We evaluated the association between vitamin D status and bone health
      in pregnant and post-partum immigrant versus Swedish women. METHODS: We
      consecutively recruited 41 immigrant and 19 age-matched healthy native Swedish
      women. Serum 25-hydroxy vitamin D(3) [25(OH)D] and parathyroid hormone (PTH) were
      analyzed at pregnancy week 12 and 6-12 months postpartum. Dual X-ray
      absorptiometry (DXA) of the hip and lumbar spine, and peripheral quantitative
      computed tomography (pQCT) of the radius and tibia were analyzed 6-12 months
      postpartum. RESULTS: The mean+/-SD 25(OH)D in gestational week 12 was 20+/-11
      nmol/L among the immigrants and 60+/-17 nmol/L among the Swedish women (p<0.001).
      The postpartum 25(OH)D was 29+/-18 nmol/L among the immigrants and 53+/-19 nmol/L
      among the Swedish women (p=0.003). BMD measured with DXA and pQCT did not differ
      significantly between groups. The ratio of cortical and trabecular density, a
      potential sign of osteomalacia, did not differ between groups. There were no
      significant correlations between 25(OH)D and the bone density measurements.
      CONCLUSIONS: Immigrant young women in Sweden are at a high risk of persistent and
      pronounced 25(OH)D deficiency. However, radiological measures of bone health were
      not affected by persisting low 25(OH)D. The health consequences of 25(OH)D
      deficiency should be studied in future studies.

PMID- 24292618
TI  - Intra- and inter-rater reliability of jumping mechanography muscle function
      assessments.
AB  - Muscle function can be assessed through jumping mechanography, where portable
      ground reaction force plates collect dynamic information as a subject jumps. The
      aim of this study was to assess both intra- and inter- rater reliability of
      jumping mechanography. Ten healthy adults underwent 3 sets of testing (collected
      by 3 different raters) at two separate sessions, one week apart. They performed a
      number of tests in each session: multiple one-legged hopping (M1LH; on right and
      left legs) and single two-legged jumps (S2LJ; with or without arm swing). The
      S2LJ assessed variables of power per body mass, jump height, velocity and
      efficiency; whereas, M1LH assessed maximum force per body mass and stiffness.
      Inter-rater coefficients of variation (CV) were less than 0.6% and 2.6% for the
      S2LJ and M1LH, respectively, for the primary outcome variables of power/body mass
      and force/body mass. Analyzing intra-rater results also produced CVs less than
      5.3% for all variables. The present study reports that the Leonardo ground
      reaction force plate system yields reproducible results between sessions, without
      significant contribution of variability from the test operator. Jumping
      mechanography is an easy, safe and reliable method for the assessment of lower
      limb musculoskeletal function. 

PMID- 24292619
TI  - The HEPHAISTOS study: compliance and adherence with a novel orthotic device for
      calf muscle unloading.
AB  - The present manuscript seeks to discuss methodological aspects regarding the
      application of the novel unloading orthosis 'HEPHAISTOS' that has been
      specifically developed to study physiological effects of muscular unloading
      without altering the impact of gravitational loading. The 'HEPHAISTOS' has been
      applied in an ambulatory clinical interventional study. During gait, the
      'HEPHAISTOS' significantly reduces activation and force production of calf
      muscles while it completely retains body mass-related force on the tibia. Eleven
      healthy male subjects participated in the study and followed their normal
      everyday lives while wearing the orthosis. Several measurement sessions have been
      performed to investigate the time course of structural and functional adaptations
      during intervention and recovery. Follow-up measurements were performed for one
      year after the intervention. In consideration of the experiences of a unique
      ambulant unloading study, organizational and methodological recommendations are
      discussed in this manuscript. Activity monitoring data obtained with portable
      accelerometers reveal unchanged gait activities and good subject compliance
      throughout the intervention. Moreover, electromyography (EMG) and motion data
      investigating gait properties on reambulation day are illustrated. These data
      show that during the initial steps following removal of 'HEPHAISTOS', gait was
      significantly asynchronous indicating an acutely altered motor control in the
      unloaded lower leg muscles. 

PMID- 24292617
TI  - Longitudinal changes in calcium and vitamin D intakes and relationship to bone
      mineral density in a prospective population-based study: the Canadian Multicentre
      Osteoporosis Study (CaMos).
AB  - OBJECTIVES: Our objective was to study changes in calcium and vitamin D intakes
      over time, and their cross-sectional and longitudinal associations with bone
      mineral density (BMD). METHODS: We followed 9382 women and men aged >=25 and 899
      aged 16-24, for 10 and 2 years respectively. RESULTS: Calcium and vitamin D
      intakes increased over time in adults, but decreased in women aged 16-18. The
      increased intakes in adults were largely attributable to the increased use of
      calcium and/or vitamin D supplements. Both the percentage of supplement users and
      average dose among users increased over time. There was nevertheless a high
      prevalence of calcium and vitamin D intake below the estimated average
      requirement. At baseline, higher calcium and vitamin D intakes were associated
      with higher total hip and femoral neck BMD in young men, and cumulatively high
      levels of calcium and vitamin D intakes over time contributed to better BMD
      maintenance at lumbar spine and hip sites in adult women. CONCLUSIONS: Although
      total intakes, particularly of vitamin D, frequently fell below the Institute of
      Medicine recommendations despite an increase over time in supplement use, we
      found some positive associations between total calcium and vitamin D intake and
      bone health.

PMID- 24292620
TI  - The effects of a varus unloader brace for lateral tibiofemoral osteoarthritis and
      valgus malalignment after anterior cruciate ligament reconstruction: a single
      case study.
AB  - We investigated the immediate effects of a varus knee brace on knee symptoms and
      knee-joint biomechanics in an individual with predominant lateral tibiofemoral
      joint osteoarthritis (TFJOA) and valgus malalignment after anterior cruciate
      ligament (ACL) reconstruction. A varus unloader brace was prescribed to a 48-year
      old male with predominant lateral radiographic and symptomatic TFJOA and valgus
      malalignment eight-years following ACL reconstruction. During a step-down task,
      the participant rated knee pain, task-difficulty, knee-stability and knee
      confidence on four separate visual analogue scales. Quantitative gait analysis
      was conducted during self-selected walking trials under three test conditions in
      a randomized order: (i) no brace; (ii) brace without frontal plane adjustment (no
      varus re-alignment); and (ii) brace with frontal plane adjustment (varus re
      alignment). Post-processing of gait data involved calculation of knee kinematics
      and net joint moments for the reconstructed limb. The participant reported
      improved pain (3%), task difficulty (41%), stability (46%) and confidence (49%)
      when performing the step-down task with the brace. The varus brace resulted in
      immediate reductions in knee abduction angle (24%) and internal rotation angle
      (56%), and increased knee adduction moment (18%). These findings provide
      preliminary evidence for potentially beneficial effects of bracing on knee
      symptoms and biomechanics in individuals with lateral TFJOA after reconstruction.

PMID- 24292621
TI  - Genetic association of rs1800780 (A->G) polymorphism of the eNOS gene with
      susceptibility to essential hypertension in a Chinese Han population.
AB  - To investigate the association of eNOS gene polymorphism with essential
      hypertension in the Chinese Han population, we examined polymorphisms of the
      rs2070744 (T->C), rs1800780 (A->G), and rs3918181 (A->G) loci. The results
      demonstrated that the genotypic frequency at the rs1800780 (A->G) locus was
      significantly different between patients with essential hypertension and the
      control cohorts (P < 0.05); while genotypic frequencies and allelic frequencies
      at rs2070744 (T->C) and rs3918181 (A->G) loci had no statistical difference
      between the patient group and controls (P > 0.05). In addition, haplotype
      analysis found a statistically significant difference for haplotype TGA, with OR
      (95% CI) of 1.549 (1.116-2.150) (P < 0.05). These findings suggest that
      polymorphism of rs1800780 (A->G) in the eNOS gene may be one of the most
      important genetic factors associated with essential hypertension susceptibility,
      and those who have haplotype TGA may be at risk to develop essential
      hypertension. 

PMID- 24292622
TI  - Effects of silver nanoparticles with different sizes on photochemical responses
      of polythiophene-fullerene thin films.
AB  - Effects of size and coverage density of silver nanoparticles (AgPs) on the
      fluorescence emission and fluorescence lifetime of poly(3-hexylthiophene-2,5
      diyl) (P3HT) thin films were investigated. AgPs of 64 nm diameter showed greater
      effects on the fluorescence decay process of P3HT films as compared with 7 nm
      AgPs. The fluorescence lifetime (FL) of P3HT decreased from 0.61 to 0.22 ns in
      the presence of 64 nm AgPs, while no appreciable change (0.60 ns) was seen in the
      case of 7 nm AgPs. The results suggest that the 64 nm AgPs showed a greater
      effect on the enhancement of the decay rate of excited P3HT. The photoelectric
      conversion of thin films consisting of P3HT and phenyl-C61-butyric acid methyl
      ester (PCBM) was also investigated. AgPs of 7 or 64 nm diameters were first
      deposited on indium-tin-oxide substrates with controlled surface coverage
      densities from ~1 to 40%. When the coverage densities of deposited AgPs were ~20%
      for both 7 and 64 nm, the enhancement of photoelectric conversion efficiency
      reached maximum. The degree of enhancement in the case of 64 nm AgPs was larger
      than in the case of 7 nm AgPs.

PMID- 24292623
TI  - The myeloma drug lenalidomide promotes the cereblon-dependent destruction of
      Ikaros proteins.
AB  - Thalidomide-like drugs such as lenalidomide are clinically important treatments
      for multiple myeloma and show promise for other B cell malignancies. The
      biochemical mechanisms underlying their antitumor activity are unknown.
      Thalidomide was recently shown to bind to, and inhibit, the cereblon ubiquitin
      ligase. Cereblon loss in zebrafish causes fin defects reminiscent of the limb
      defects seen in children exposed to thalidomide in utero. Here we show that
      lenalidomide-bound cereblon acquires the ability to target for proteasomal
      degradation two specific B cell transcription factors, Ikaros family zinc finger
      proteins 1 and 3 (IKZF1 and IKZF3). Analysis of myeloma cell lines revealed that
      loss of IKZF1 and IKZF3 is both necessary and sufficient for lenalidomide's
      therapeutic effect, suggesting that the antitumor and teratogenic activities of
      thalidomide-like drugs are dissociable. 

PMID- 24292624
TI  - Drosophila life span and physiology are modulated by sexual perception and
      reward.
AB  - Sensory perception can modulate aging and physiology across taxa. We found that
      perception of female sexual pheromones through a specific gustatory receptor
      expressed in a subset of foreleg neurons in male fruit flies, Drosophila
      melanogaster, rapidly and reversibly decreases fat stores, reduces resistance to
      starvation, and limits life span. Neurons that express the reward-mediating
      neuropeptide F are also required for pheromone effects. High-throughput whole
      genome RNA sequencing experiments revealed a set of molecular processes that were
      affected by the activity of the longevity circuit, thereby identifying new
      candidate cell-nonautonomous aging mechanisms. Mating reversed the effects of
      pheromone perception; therefore, life span may be modulated through the
      integrated action of sensory and reward circuits, and healthy aging may be
      compromised when the expectations defined by sensory perception are discordant
      with ensuing experience. 

PMID- 24292627
TI  - The missing mountain water: slower westerlies decrease orographic enhancement in
      the Pacific Northwest USA.
AB  - Trends in streamflow timing and volume in the Pacific Northwest United States
      have been attributed to increased temperatures, because trends in precipitation
      at lower-elevation stations were negligible. We demonstrate that observed
      streamflow declines are probably associated with declines in mountain
      precipitation, revealing previously unexplored differential trends. Lower
      troposphere winter (November to March) westerlies are strongly correlated with
      high-elevation precipitation but weakly correlated with low-elevation
      precipitation. Decreases in lower-tropospheric winter westerlies across the
      region from 1950 to 2012 are hypothesized to have reduced orographic
      precipitation enhancement, yielding differential trends in precipitation across
      elevations and contributing to the decline in annual streamflow. Climate
      projections show weakened lower-troposphere zonal flow across the region under
      enhanced greenhouse forcing, highlighting an additional stressor that is relevant
      for climate change impacts on hydrology. 

PMID- 24292626
TI  - Males shorten the life span of C. elegans hermaphrodites via secreted compounds.
AB  - How an individual's longevity is affected by the opposite sex is still largely
      unclear. In the nematode Caenorhabditis elegans, the presence of males
      accelerated aging and shortened the life span of individuals of the opposite sex
      (hermaphrodites), including long-lived or sterile hermaphrodites. The male
      induced demise could occur without mating and required only exposure of
      hermaphrodites to medium in which males were once present. Such communication
      through pheromones or other diffusible substances points to a nonindividual
      autonomous mode of aging regulation. The male-induced demise also occurred in
      other species of nematodes, suggesting an evolutionary conserved process whereby
      males may induce the disposal of the opposite sex to save resources for the next
      generation or to prevent competition from other males. 

PMID- 24292625
TI  - Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma
      cells.
AB  - Lenalidomide is a drug with clinical efficacy in multiple myeloma and other B
      cell neoplasms, but its mechanism of action is unknown. Using quantitative
      proteomics, we found that lenalidomide causes selective ubiquitination and
      degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN
      CRL4 ubiquitin ligase. IKZF1 and IKZF3 are essential transcription factors in
      multiple myeloma. A single amino acid substitution of IKZF3 conferred resistance
      to lenalidomide-induced degradation and rescued lenalidomide-induced inhibition
      of cell growth. Similarly, we found that lenalidomide-induced interleukin-2
      production in T cells is due to depletion of IKZF1 and IKZF3. These findings
      reveal a previously unknown mechanism of action for a therapeutic agent:
      alteration of the activity of an E3 ubiquitin ligase, leading to selective
      degradation of specific targets. 

PMID- 24292628
TI  - First-photon imaging.
AB  - Imagers that use their own illumination can capture three-dimensional (3D)
      structure and reflectivity information. With photon-counting detectors, images
      can be acquired at extremely low photon fluxes. To suppress the Poisson noise
      inherent in low-flux operation, such imagers typically require hundreds of
      detected photons per pixel for accurate range and reflectivity determination. We
      introduce a low-flux imaging technique, called first-photon imaging, which is a
      computational imager that exploits spatial correlations found in real-world
      scenes and the physics of low-flux measurements. Our technique recovers 3D
      structure and reflectivity from the first detected photon at each pixel. We
      demonstrate simultaneous acquisition of sub-pulse duration range and 4-bit
      reflectivity information in the presence of high background noise. First-photon
      imaging may be of considerable value to both microscopy and remote sensing. 

PMID- 24292629
TI  - Thermodynamic analysis of osmolyte effect on thermal stability of ribonuclease A
      in terms of water activity.
AB  - Thermal unfolding of ribonuclease A (RNase) was analyzed in various osmolyte
      solutions of glycine, proline, sarcosine, N,N-dimethylglycine, betaine, myo
      inositol, taurine, and trimethylamine-N-oxide (TMAO). All the osmolytes tested
      stabilized the protein. The thermal unfolding curve was described well by the
      van't Hoff equation and the melting temperature and the enthalpy of protein
      unfolding were obtained. The Wyman-Tanford equation, which describes the unfolded
      to-folded protein ratio as a function of water activity, was successfully applied
      to obtain a linear plot. In consideration of this experimentally obtained
      linearity, the Wyman-Tanford plot could be integrated to calculate the
      stabilization free energy of the protein (??G) in the solution. The ??G was
      proved to be described by the property of the microstructure around the protein
      surface, which is composed of the protein hydration, the cosolute-binding, and
      the preferential exclusion, and the property of the bulk solution; water
      activity. The m-values of osmolytes for protein unfolding were obtained from ??G
      calculated. Among the osmolytes tested, myo-inositol showed the highest m-value. 

PMID- 24292630
TI  - Neural-specific expression of miR-344-3p during mouse embryonic development.
AB  - MicroRNAs are small noncoding RNAs involved in various biological processes. We
      characterized the expression of miR-344-3p during mouse embryonic development. At
      E9.5-E10.5 and E15.5, in situ hybridization detected strong miR-344-3p signal in
      the central nervous system, including the cerebral cortex, hindbrain, cerebellum,
      thalamus, hindbrain, medulla oblongata, spinal cord, and dorsal root ganglia.
      Further, qRT-PCR analysis identified miR-344-3p expression at E15.5, with
      expression stably maintained in the brain from E12.5 to E18.5 before decreasing
      to relatively low levels postnatally. We also analyzed miR-344-3p expression
      using immunofluorescence in situ hybridization at E18.5 and within the adult
      brain. miR-344-3p signal was mainly detected in cortical regions surrounding the
      ventricular system, choroid plexus, glomerular layer of the olfactory bulb, and
      granular cell layer of the cerebellar cortex. Altogether, our results indicate
      miR-344-3p may play an important role in morphogenesis, nervous system
      development in the brain. 

PMID- 24292631
TI  - Interlayer micromechanics of the aortic heart valve leaflet.
AB  - While the mechanical behaviors of the fibrosa and ventricularis layers of the
      aortic valve (AV) leaflet are understood, little information exists on their
      mechanical interactions mediated by the GAG-rich central spongiosa layer.
      Parametric simulations of the interlayer interactions of the AV leaflets in
      flexure utilized a tri-layered finite element (FE) model of circumferentially
      oriented tissue sections to investigate inter-layer sliding hypothesized to
      occur. Simulation results indicated that the leaflet tissue functions as a
      tightly bonded structure when the spongiosa effective modulus was at least 25 %
      that of the fibrosa and ventricularis layers. Novel studies that directly
      measured transmural strain in flexure of AV leaflet tissue specimens validated
      these findings. Interestingly, a smooth transmural strain distribution indicated
      that the layers of the leaflet indeed act as a bonded unit, consistent with our
      previous observations (Stella and Sacks in J Biomech Eng 129:757-766, 2007) of a
      large number of transverse collagen fibers interconnecting the fibrosa and
      ventricularis layers. Additionally, when the tri-layered FE model was refined to
      match the transmural deformations, a layer-specific bimodular material model
      (resulting in four total moduli) accurately matched the transmural strain and
      moment-curvature relations simultaneously. Collectively, these results provide
      evidence, contrary to previous assumptions, that the valve layers function as a
      bonded structure in the low-strain flexure deformation mode. Most likely, this
      results directly from the transverse collagen fibers that bind the layers
      together to disable physical sliding and maintain layer residual stresses.
      Further, the spongiosa may function as a general dampening layer while the AV
      leaflets deforms as a homogenous structure despite its heterogeneous
      architecture.

PMID- 24292632
TI  - Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia
      inducible factor-1 alpha (HIF-1alpha), in patients with refractory solid tumors.
AB  - PURPOSE: Hypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal
      and tumor tissues to oxygen deprivation. HIF-1 is frequently overexpressed in
      cancer cells, where it is involved in the upregulation of many genes necessary
      for survival. EZN-2968 is an antisense oligodeoxynucleotide that specifically
      targets HIF-1alpha, one of the subunits of HIF-1. We conducted a trial of EZN
      2968 in patients with refractory solid tumors to evaluate antitumor response and
      to measure modulation of HIF-1alpha mRNA and protein levels as well as HIF-1
      target genes. METHODS: Adult patients with refractory advanced solid tumors were
      administered EZN-2968 as a 2-h IV infusion at a dose of 18 mg/kg once a week for
      three consecutive weeks followed by 3-week off; in a 6-week cycle. Tumor biopsies
      and dynamic contrast enhanced MRI (DCE-MRI) were performed at baseline and after
      the third dose. RESULTS: Ten patients were enrolled, of whom all were evaluable
      for response; one patient with a duodenal neuroendocrine tumor had prolonged
      stabilization of disease (24 weeks). Reduction in HIF-1alpha mRNA levels compared
      to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies.
      Reductions in levels of HIF-1alpha protein and mRNA levels of some target genes
      were observed in two patients. Quantitative analysis of DCE-MRI from two patients
      revealed changes in K (trans) and k ep. The trial was closed prematurely when the
      sponsor suspended development of this agent. CONCLUSION: This trial provides
      preliminary proof of concept for modulation of HIF-1alpha mRNA and protein
      expression and target genes in tumor biopsies following the administration of EZN
      2968.

PMID- 24292633
TI  - Microfluidic evaluation of red cells collected and stored in modified processing
      solutions used in blood banking.
AB  - The most recent American Association of Blood Banks survey found that 40,000
      units of blood are required daily for general medicine, hematology/oncology,
      surgery, and for accident and trauma victims. While blood transfusions are an
      extremely important component of critical healthcare, complications associated
      with transfusion of blood components still exist. It is well-established that the
      red blood cell (RBC) undergoes many physical and chemical changes during storage.
      Increased oxidative stress, formation of advanced glycation endproducts, and
      microparticle formation are all known to occur during RBC storage. Furthermore,
      it is also known that patients who receive a transfusion have reduced levels of
      available nitric oxide (NO), a major determinant in blood flow. However, the
      origin of this reduced NO bioavailability is not completely understood. Here, we
      show that a simple modification to the glucose concentration in the solutions
      used to process whole blood for subsequent RBC storage results in a remarkable
      change in the ability of these cells to stimulate NO. In a controlled in vitro
      microflow system, we discovered that storage of RBCs in normoglycemic versions of
      standard storage solutions resulted in RBC-derived ATP release values 4 weeks
      into storage that were significantly greater than day 1 release values for those
      RBCs stored in conventional solutions. During the same storage duration,
      microfluidic technologies enabled measurements of endothelium-derived NO that
      were stimulated by the ATP release from the stored RBCs. In comparison to
      currently accepted processing solutions, the NO production increased by more than
      25% in the presence of the RBCs stored in the normoglycemic storage solutions.
      Control experiments using inhibitors of ATP release from the RBCs, or ATP binding
      to the endothelium, strongly suggest that the increased NO production by the
      endothelium is directly related to the ability of the stored RBCs to release ATP.
      We anticipate these findings to represent a starting point in controlling glucose
      levels in solutions used for blood component storage, especially considering that
      current solutions contain glucose at levels that are nearly 20-fold greater than
      blood glucose levels of a healthy human, and even 10-fold greater than levels
      found in diabetic bloodstreams.

PMID- 24292635
TI  - Accurate and robust molecular crystal modeling using fragment-based electronic
      structure methods.
AB  - Accurately modeling molecular crystal polymorphism requires careful treatment of
      diverse intra- and intermolecular interactions which can be difficult to achieve
      without the use of high-level ab initio electronic structure techniques. Fragment
      based methods like the hybrid many-body interaction QM/MM technique enable the
      application of accurate electronic structure models to chemically interesting
      molecular crystals. The theoretical underpinnings of this approach and the
      practical requirements for the QM and MM contributions are discussed. Benchmark
      results and representative applications to aspirin and oxalyl dihydrazide
      crystals are presented. 

PMID- 24292634
TI  - Pharmacological inhibition of NOX reduces atherosclerotic lesions, vascular ROS
      and immune-inflammatory responses in diabetic Apoe(-/-) mice.
AB  - AIMS/HYPOTHESIS: Enhanced vascular inflammation, immune cell infiltration and
      elevated production of reactive oxygen species (ROS) contribute significantly to
      pro-atherogenic responses in diabetes. We assessed the immunomodulatory role of
      NADPH oxidase (NOX)-derived ROS in diabetes-accelerated atherosclerosis. METHODS:
      Diabetes was induced in male Apoe(-/-) mice with five daily doses of
      streptozotocin (55 mg kg(-1) day(-1)). Atherosclerotic plaque size, markers of
      ROS and immune cell accumulation were assessed in addition to flow cytometric
      analyses of cells isolated from the adjacent mediastinal lymph nodes (meLNs). The
      role of NOX-derived ROS was investigated using the NOX inhibitor, GKT137831 (60
      mg/kg per day; gavage) administered to diabetic and non-diabetic Apoe(-/-) mice
      for 10 weeks. RESULTS: Diabetes increased atherosclerotic plaque development in
      the aortic sinus and this correlated with increased lesional accumulation of T
      cells and CD11c(+) cells and altered T cell activation in the adjacent meLNs.
      Diabetic Apoe(-/-) mice demonstrated an elevation in vascular ROS production and
      expression of the proinflammatory markers monocyte chemoattractant protein 1,
      vascular adhesion molecule 1 and IFNgamma. Blockade of NOX-derived ROS using
      GKT137831 prevented the diabetes-mediated increase in atherosclerotic plaque area
      and associated vascular T cell infiltration and also significantly reduced
      vascular ROS as well as markers of inflammation and plaque necrotic core area.
      CONCLUSIONS/INTERPRETATION: Diabetes promotes pro-inflammatory immune responses
      in the aortic sinus and its associated lymphoid tissue. These changes are
      associated with increased ROS production by NOX. Blockade of NOX-derived ROS
      using the NOX inhibitor GKT137831 is associated with attenuation of these changes
      in the immune response and reduces the diabetes-accelerated development of
      atherosclerotic plaques in Apoe(-/-) mice.

PMID- 24292637
TI  - Prevalence and correlates of suicidal ideation among parolees.
AB  - OBJECTIVE: This study examined the prevalence and correlates of suicidal ideation
      among parolees and among persons who were not on parole. METHODS: Three years of
      data (2009 to 2011) from the National Survey on Drug Use and Health were
      analyzed. Data on sociodemographic and clinical characteristics and violent
      behaviors of parolees (N=1,249) and nonparolees (N=114,033) were examined as
      indicators of need and as predictors of suicidal ideation. Multivariate logistic
      regression analysis was conducted, using suicidal ideation as the dependent
      variable. RESULTS: Over the three years, the average prevalence of suicidal
      ideation among parolees (8.6%) was more than twice that among nonparolees (3.7%).
      Characteristics associated with decreased suicidal ideation among nonparolees,
      such as being married, older, and employed, were not related to lower suicidal
      ideation among parolees. For parolees, having health insurance decreased the
      likelihood of suicidal ideation by 50%. Parolees who received a past-year
      prescription for a mood disorder did not have higher rates of suicidal ideation,
      although this variable was associated with higher suicidal ideation among
      nonparolees. Parolees were significantly more likely than nonparolees to rate
      their health as poor (4.1% versus 2.6%). CONCLUSIONS: Results indicated that
      parolees have more life stressors and that providing them with access to health
      care might lower suicidal ideation. Because parolees were more likely to rate
      their health as poor, providing access to medical care may improve their quality
      of life and their chance of successful return to the community.

PMID- 24292636
TI  - Electrocardiographic left ventricular hypertrophy Cornell product is a feasible
      predictor of cardiac prognosis in patients with chronic heart failure.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for
      cardiovascular disease and is associated with heart failure development. The
      Cornell product is an easily measured electrocardiographic parameter for
      assessing LVH. However, it is undetermined whether the Cornell product can
      predict the cardiac prognosis of chronic heart failure (CHF) patients. METHODS
      AND RESULTS: We performed standard 12-lead electrocardiography and calculated the
      Cornell product in 432 consecutive CHF patients. LV geometry was assessed as
      normal, concentric remodeling, concentric or eccentric hypertrophy. The Cornell
      product was significantly higher in patients with eccentric hypertrophy, and
      increased with advancing New York Heart Association functional class. During a
      median follow-up of 660 days, there were 121 cardiac events including 36 cardiac
      deaths and 85 re-hospitalizations for worsening heart failure. Multivariate Cox
      proportional hazard analysis showed that the Cornell product was an independent
      predictor of cardiac events in CHF patients. Patients in the highest quartile of
      Cornell product had a higher prevalence of LV eccentric hypertrophy (22, 29, 33
      and 67 % for quartiles one through four). Kaplan-Meier analysis demonstrated that
      the highest quartile of Cornell product was associated with the greatest risk
      among CHF patients. CONCLUSION: The Cornell product is associated with LV
      eccentric hypertrophy and can be used to predict future cardiac events in CHF
      patients.

PMID- 24292638
TI  - Reduced circulating endothelial progenitor cells in thromboangiitis obliterans
      (Buerger's disease).
AB  - To determine the role of endothelial progenitor cells (EPCs) in the pathogenesis
      of thromboangiitis obliterans (TAO), EPC numbers and colony-forming units,
      migratory function and tubular structure formation in vitro were compared between
      13 young male TAO patients and two age-matched healthy control groups: 11 smokers
      and 12 non-smokers. TAO patients had significantly lower numbers of EPCs and EPC
      colonies compared to both non-smokers [190 (97.0-229) vs 528 (380-556), p < 0.001
      for EPCs and 0.80 (0.53-1.00) vs 2.80 (2.08-4.00) per mm(2), p = 0.001 for EPC
      colonies] and smokers [190 (97.0-229) vs 272 (229-326), p = 0.012 for EPCs and
      0.80 (0.53-1.00) vs 2.80 (1.80-3.93) per mm(2), p = 0.001 for EPC colonies].
      However, there were no significant differences in migratory function or tube
      formation between the three groups. These results suggest that TAO patients have
      an intrinsic decrease in EPCs not entirely associated with smoking, which may be
      the cause of endothelial dysfunction seen in TAO patients leading to the
      development of this disease at early ages. 

PMID- 24292639
TI  - Correlates of reactive hyperemic index in men and postmenopausal women.
AB  - The aim of the present study was to investigate the differences in digital
      reactive hyperemic index (RHI) in men and postmenopausal women. We investigated
      the differences in and correlates of RHI, measured by peripheral artery tonometry
      (PAT), in a group of 82 men (mean age +/- SD: 55.6 +/- 8.2 years; body mass
      index: 29.0 +/- 4.2 kg/m(2)) and 125 postmenopausal women (58.9 +/- 5.2 years;
      27.7 +/- 4.1 kg/m(2)). We also examined fRHI values (natural log of the PAT ratio
      of the 90-120 seconds post-occlusion interval) and augmentation index (AIx) as a
      measure of arterial stiffness. We found that RHI, fRHI and AIx were significantly
      lower in men compared to postmenopausal women (p<0.0001). We also found that fRHI
      values were significantly lower in individuals with (MetS+) versus without (MetS
      ) the metabolic syndrome (MetS). Endothelial inflammation was present in MetS+
      subjects as indicated by increased plasma soluble intercellular adhesion molecule
      1 (sICAM-1) (p<0.001) and E-selectin (p=0.0519) concentrations compared to MetS-
      individuals. No significant difference was found in RHI or AIx between MetS+
      versus MetS- individuals. In summary, our study reveals that men have an
      impairment of endothelial function, assessed by digital PAT, compared to
      postmenopausal women. Furthermore, we show that the presence of the MetS is
      characterized by endothelial dysfunction, as suggested by lower fRHI, as well as
      by endothelial inflammation, which likely contributes to the increased
      cardiovascular disease risk associated with the MetS. ClinicalTrials.gov
      Identifier: NCT01085019. 

PMID- 24292640
TI  - International ABI awareness as the next step in the PAD campaign.

PMID- 24292641
TI  - Allometric scaling of endothelium-dependent vasodilation: brachial artery flow
      mediated dilation coming of age?

PMID- 24292642
TI  - Five keys for diagnosing most vertigo, dizziness, and imbalance syndromes: an
      expert opinion.

PMID- 24292643
TI  - Cortical dysfunction in cerebellar ataxia with antibodies to glutamic acid
      decarboxylase.

PMID- 24292644
TI  - Association of sleep apnea with clinically silent microvascular brain tissue
      changes in acute cerebral ischemia.
AB  - The aim of this study was to determine the importance of sleep apnea in relation
      to clinically silent microvascular brain tissue changes in patients with acute
      cerebral ischemia. Patients with acute cerebral ischemia prospectively underwent
      nocturnal respiratory polygraphy within 5 days from symptom-onset. Sleep apnea
      was defined as apnea-hypopnea-index (AHI) >=5/h. Experienced readers blinded to
      clinical and sleep-related data reviewed brain computed tomography and magnetic
      resonance imaging scans for leukoaraiosis and chronic lacunar infarctions.
      Ischemic lesions were considered clinically silent when patients did not recall
      associated stroke-like symptoms. Functional outcome was assessed with modified
      Rankin Scale at discharge, 6 and 12 months. Fifty-one of 56 (91 %) patients had
      sleep apnea of any degree. Patients with moderate-to-severe leukoaraiosis
      (Wahlund score >=5) were found to have higher mean AHI than those with none or
      mild leukoaraiosis (34.4 vs. 12.8/h, p < 0.001). Moderate-to-severe sleep apnea
      (AHI >=15/h) was found to be an independent predictor of moderate-to-severe
      leukoaraiosis (adjusted OR 6.03, 95 % CI 1.76-20.6, p = 0.0042) and of moderate
      to-severe leukoaraiosis associated with clinically silent chronic lacunar
      infarctions (adjusted OR 10.5, 95 % CI 2.19-50.6, p = 0.003). The higher the
      Wahlund score and the AHI, the more likely unfavorable functional outcome
      resulted over time (p = 0.0373). In acute cerebral ischemia, sleep apnea is
      associated with clinically silent microvascular brain tissue changes and may
      negatively influence functional outcome. Routine sleep apnea screening and
      further investigation of possible long-term effects of non-invasive ventilatory
      treatment of sleep apnea appear warranted in this at-risk population. 

PMID- 24292645
TI  - Energetic analysis of the rhodopsin-G-protein complex links the alpha5 helix to
      GDP release.
AB  - We present a model of interaction of Gi protein with the activated receptor (R*)
      rhodopsin, which pinpoints energetic contributions to activation and reconciles
      the beta2 adrenergic receptor-Gs crystal structure with new and previously
      published experimental data. In silico analysis demonstrated energetic changes
      when the Galpha C-terminal helix (alpha5) interacts with the R* cytoplasmic
      pocket, thus leading to displacement of the helical domain and GDP release. The
      model features a less dramatic domain opening compared with the crystal
      structure. The alpha5 helix undergoes a 63 degrees  rotation, accompanied by a
      5.7-A translation, that reorganizes interfaces between alpha5 and alpha1 helices
      and between alpha5 and beta6-alpha5. Changes in the beta6-alpha5 loop displace
      alphaG. All of these movements lead to opening of the GDP-binding pocket. The
      model creates a roadmap for experimental studies of receptor-mediated G-protein
      activation. 

PMID- 24292647
TI  - Synthesis and electrocatalytic properties of PtBi nanoplatelets and PdBi
      nanowires.
AB  - We have demonstrated a one-pot, facile and rapid strategy to synthesize novel
      PtBi nanoplatelets (NPLs) and PdBi nanowires (NWs) with controlled shape, size,
      and composition in the presence of oleylamine (OAm) and NH4Br. In contrast to the
      conventional face centered cubic (fcc) structure of Pt-based NPs, PtBi possesses
      a chemically ordered intermetallic hexagonal close packed (hcp) structure. Using
      this uniaxial crystal structural character of PtBi, we succeed in synthesizing
      two-dimensional (2-D) PtBi NPLs. Significantly, the electrochemical studies
      indicate that the as-prepared 2-D PtBi NPLs exhibit enhanced electrocatalytic
      activity toward formic acid and methanol oxidation with larger oxidation current
      density, higher tolerance to CO poisoning, and more negative onset potential in
      comparison with the commercial Pt/C catalyst. This is attributed to the addition
      of second metal Bi. In addition, to the best of our knowledge, this is the first
      time that synthesis of one-dimensional (1-D) PdBi alloy NWs has been reported.
      The as-synthesized 1-D PdBi bimetallic NWs may find promising potential
      applications in various fields, such as fuel cells, electrochemical sensors, and
      organocatalysis. 

PMID- 24292646
TI  - Structural basis for processive DNA synthesis by yeast DNA polymerase E.
AB  - DNA polymerase E (Pol E) is a high-fidelity polymerase that has been shown to
      participate in leading-strand synthesis during DNA replication in eukaryotic
      cells. We present here a ternary structure of the catalytic core of Pol E (142
      kDa) from Saccharomyces cerevisiae in complex with DNA and an incoming
      nucleotide. This structure provides information about the selection of the
      correct nucleotide and the positions of amino acids that might be critical for
      proofreading activity. Pol E has the highest fidelity among B-family polymerases
      despite the absence of an extended beta-hairpin loop that is required for high
      fidelity replication by other B-family polymerases. Moreover, the catalytic core
      has a new domain that allows Pol E to encircle the nascent double-stranded DNA.
      Altogether, the structure provides an explanation for the high processivity and
      high fidelity of leading-strand DNA synthesis in eukaryotes. 

PMID- 24292648
TI  - Determination of transgene copy number in stably transfected mammalian cells by
      PCR-capillary electrophoresis assay.
AB  - The quantitative determination of transgene copy number in stably transfected
      mammalian cells has been traditionally estimated by Southern blot analysis.
      Recently, other methods have become available for appraisal of gene copy number,
      such as real-time PCR. Herein we describe a new method based on a fluorescently
      labeled PCR, followed by capillary electrophoresis. We amplified our target gene
      (prothrombin) and the internal control originating from genomic DNA (18S rRNA) in
      the same PCR tube and calculated the mean peak height ratio of the target:control
      gene for every cell clone sample. With this approach we identified stably
      transfected cell clones bearing the same transgene copy number. The results of
      our assay were confirmed by real-time PCR. Our method proves to be fast, low
      cost, and reproducible compared with traditionally used methods. This assay can
      be used as a rapid screening tool for the determination of gene copy number in
      gene expression experiments. 

PMID- 24292649
TI  - Antimicrobial and antioxidant activities with acute toxicity, cytotoxicity and
      mutagenicity of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the coast
      of Urla (Izmir, Turkey).
AB  - The aim of the study was to evaluate the biological activities with toxic
      properties of the methanol, hexane, and chloroform extracts of Cystoseira
      compressa (Esper) Gerloff & Nizamuddin from the Coast of Urla in the Aegean Sea.
      The extracts of C. compressa were tested for their antimicrobial and antioxidant
      activities in this study. Cytotoxic and mutagenic potentials of the extracts were
      also evaluated using cell culture and mutagenicity assays. Hexane extract was
      found to have higher total flavonoid and phenolic contents than the other
      extracts and exerted higher antioxidant activity than other extracts. All
      extracts exhibited moderate antimicrobial activity against tested microorganisms
      (minimum inhibitory concentration ranges are 32-256 MUg/mL). The results
      indicated that the extracts had no significant cytotoxic activity against human
      hepatocellular carcinoma Hep 3B cell line in all treated concentrations (5-50
      MUg/mL) and did not show mutagenicity in the Ames test. Lethality was not
      observed among mice treated with oral doses of the extracts. In conclusion,
      results of investigations indicate that brown alga C. compressa is a natural
      source of antioxidant. It has moderate antimicrobial activities with no toxicity.

PMID- 24292650
TI  - Common genetic factors influence hand strength, processing speed, and working
      memory.
AB  - BACKGROUND: It is important to detect cognitive decline at an early stage,
      especially before onset of mild cognitive impairment and dementia. Processing
      speed and working memory are aspects of cognitive function that are associated
      with cognitive decline. Hand strength is an inexpensive, easily measurable
      indicator of cognitive decline. However, associations between hand strength,
      processing speed, and working memory have not been studied. In addition, the
      genetic and environmental structure of the association between hand strength and
      cognitive decline is unclear. We investigated phenotypic associations between
      hand strength, processing speed, and working memory and examined the genetic and
      environmental structure of the associations between phenotypes. METHODS: Hand
      strength, processing speed (digit symbol performance), and working memory (digit
      span performance) were examined in monozygotic and dizygotic twin pairs.
      Generalized estimating equations were used to identify phenotypic associations,
      and structural equation modeling was used to investigate the genetic and
      environmental structure of the association. RESULTS: Generalized estimating
      equations showed that hand strength was phenotypically associated with digit
      symbol performance but not with digit span performance. Structural equation
      modeling showed that common genetic factors influenced hand strength and digit
      symbol and digit span performance. CONCLUSIONS: There was a phenotypic
      association between hand strength and processing speed. In addition, some genetic
      factors were common to hand strength, processing speed, and working memory.

PMID- 24292651
TI  - Genome-wide analysis of the WD-repeat protein family in cucumber and Arabidopsis.
AB  - The WD-repeat (WDR) proteins comprise an astonishingly diverse superfamily of
      regulatory proteins. To date, genome-wide characterization of this family has
      only been conducted in Arabidopsis and little is known about WDR genes in
      cucumber (Cucumis sativus L.). This study identified 191 cucumber WDR genes in
      the latest cucumber genome and the CsWDR family contained a smaller number of
      identified genes compared to Arabidopsis. The results of this study were also
      supported by genome distribution and gene duplication analysis. Phylogenetic
      analysis showed that the WDR proteins could be classified into 21 subgroups.
      Moreover, an additional 12 AtWDR proteins were also identified and a complete
      overview of this gene family in Arabidopsis is presented, including the
      phylogeny, chromosome locations and duplication events. In addition, a
      comparative analysis between these genes in cucumber and Arabidopsis was
      performed and it suggested that there was strong gene conservation and that there
      was an expansion of particular functional genes during the evolution of the two
      species. The transcript abundance level analysis during abiotic stress (NaCl, ABA
      and low temperature treatments) identified six CsWDR genes that responded to one
      or more treatments. Tissue-specific expression profiles of these six genes were
      also analyzed. This study has produced a comparative genomics analysis of the WDR
      gene family in cucumber and Arabidopsis and provides the first steps towards the
      selection of CsWDR genes for cloning and functional dissection that can be used
      in further studies into their roles in cucumber stress resistance.

PMID- 24292653
TI  - Coexisting right nonrecurrent and right recurrent inferior laryngeal nerves: a
      rare and controversial entity: report of a case and review of the literature.
AB  - Variations in the course of the recurrent laryngeal nerve (RLN) can occur,
      including the development of a nonrecurrent inferior laryngeal nerve (NRILN).
      Rarely, both a right RLN and a right NRILN have been reported in the same
      patient, merging before they enter the larynx. A case is presented, including
      images, and the literature concerning this rare anatomical finding is reviewed,
      including studies suggesting alternative explanations for these cases. Fourteen
      previously reported cases of coexisting RLN and NRILN were identified, all
      involving the right side. Some cases were associated with an anomalous origin of
      the right subclavian artery and some were not. The alternative explanations that
      a communicating branch of the sympathetic nerve, which joins the RLN, is mistaken
      for an NRILN or that a collateral branch from an NRILN is mistaken for an RLN in
      these cases are also considered. Surgeons must be aware of these unusual
      variations to minimize nerve injury during neck surgery. 

PMID- 24292652
TI  - Elastography for hepato-biliary-pancreatic surgery.
AB  - Palpation is a subjective and non-sharable diagnostic method. Recently, palpation
      has been supported and replaced by elastography, which provides a novel parameter
      of "stiffness" as a visual representation or quantified value. Today,
      elastography is performed using two major modalities: strain elastography and
      shear wave elastography. Strain elastography converts the extent of deformation
      during external compression into colors, displaying these colors as a strain map
      in a motion picture representing the relative elasticity inside the region of
      interest. Shear wave elastography can quantify the elasticity of a target by
      calculating the velocity of shear waves generated by a probe. In addition to
      superficial organs, elastography has also been applied to upper abdominal organs,
      including the liver, pancreas and spleen. The visualization of the stiffness of
      focal lesions in the liver or the pancreas has enabled a more sensitive and
      specific depiction of small, non-palpable nodules, which are difficult to depict
      using B-mode ultrasonography. The quantification of stiffness also enables non
      invasive estimates of liver fibrosis, the risk of postoperative liver
      insufficiency and the risk of recurrence of viral hepatitis after
      transplantation. In this article, we review the major reports that have recently
      been published describing the effective application of elastography to solid
      upper abdominal organs in a clinical setting. 

PMID- 24292654
TI  - New operative strategy for refractory microcystic lymphangioma.
AB  - The optimal management of microcystic lymphatic malformations (LMs) in children
      has not been established. We describe how we used the LigasureTM Vessel Sealing
      System (LVSS) to achieve partial resection of refractory microcystic LMs in a 1
      year-old boy. The child was admitted in respiratory distress caused by infection
      and swelling of cervical LMs. The LMs had been diagnosed prenatally, but had not
      decreased in size despite three treatments with OK-432 sclerotherapy. We
      performed direct dissection of the microcystic LMs using the LVSS with minimal
      intraoperative blood loss or lymphatic leakage. The LMs were resected as
      completely as possible without damage to the jugular vein or major nerves. His
      postoperative course was uneventful. Histological examination revealed complete
      sealing of the lymphovascular channels with obliterated lumens. Resection using
      the LVSS is effective and easy to perform for partial resection of microcystic
      LMs. We recommend the combination of initial OK-432 injection therapy and
      subsequent partial resection using the LVSS for refractory microcystic LMs. 

PMID- 24292655
TI  - Measuring residual dipolar couplings at high hydrostatic pressure: robustness of
      alignment media to high pressure.
AB  - Among other perturbations, high hydrostatic pressure has proven to be a mild yet
      efficient way to unfold proteins. Combining pressure perturbation with NMR
      spectroscopy allows for a residue-per-residue description of folding reactions.
      Accessing the full power of NMR spectroscopy under pressure involves the
      investigation of conformational sampling using orientational restraints such as
      residual dipolar couplings (RDCs) under conditions of partial alignment. The aim
      of this study was to identify and characterize stable and pressure resistant
      alignment media for measurement of RDCs at high pressure. Four alignment media
      were tested. A C12E5/n-hexanol alcohol mixture remains stable from 1 to 2,500
      bar, whereas Pf1 phage and DNA nanotubes undergo a reversible transition between
      300 and 900 bar. Phospholipid bicelles are stable only until 300 bar at ambient
      temperature. Hence, RDCs can be measured at high pressure, and their
      interpretation will provide atomic details of the structural and dynamic
      perturbations on unfolded or partially folded states of proteins under pressure.

PMID- 24292656
TI  - Aneuploidy analysis of non-pronuclear embryos from IVF with use of array CGH: a
      case report.
AB  - By using array comparative genomic hybridization (array CGH), to analyze the
      aneuploidy of the single blastomeres from non-pronuclear embryos on cleavage
      stage in IVF cycle. Four non-pronuclear embryos were got from an IVF cycle, and
      the each single cell was biopsied from the four cleavage-stage embryos on the
      third day after the insemination which was investigated by using array CGH. After
      the biopsy, all the embryos continued to cleave, and lately entered the morula
      stage on the fifth day, just one embryo 3 was developed to early blastocyst stage
      on the sixth day. The four blastomere 24 chromosomes showed one X monomer and
      three normal XY diploids; the autosome chromosomes of blastomeres were abnormally
      gained or lost at different chromosome from four embryos, such as Embryo 1 : 49,X
      (-1, -5, -11, -19, -20, -21, -Y, +3, +6, +7, +8, +10, +13, +14, +16, +17, +18);
      Embryo 2 : 44,XY (-12, -15); Embryo 3: 47,XY (-3, -8, -9, -21, +7, +17, +18, +19,
      +20); Embryo 4 : 54,XY (+4, +7, +10, +12, +13, +16, +17, +22). With the use of
      the array CGH, the aneuploidy analysis could review the abnormal chromosomes of
      single blastomere from the non-pronuclear embryos, which can harbor the risk of
      abnormal sex chromosome and autosome chromosomes. 

PMID- 24292657
TI  - Autophagy is Impaired in the Tibialis Anterior of Dystrophin Null Mice.
AB  - Background Duchenne muscular dystrophy is a lethal, progressive, muscle-wasting
      disease caused by mutations in the DMD gene. Structural remodelling processes are
      responsible for muscle atrophy and replacement of myofibers by fibrotic and
      adipose tissues. Molecular interventions modulating catabolic pathways, such as
      the ubiquitin-proteasome and the autophagy-lysosome systems, are under
      development for Duchenne and other muscular dystrophies. The Akt signaling
      cascade is one of the main pathways involved in protein synthesis and autophagy
      repression and is known to be up-regulated in dystrophin null mdx mice. Results
      We report that autophagy is triggered by fasting in the tibialis anterior muscle
      of control mice but not in mdx mice. Mdx mice show persistent Akt activation upon
      fasting and failure to increase the expression of FoxO3 regulated autophagy and
      atrophy genes, such as Bnip3 and Atrogin1. We also provide evidence that
      autophagy is differentially regulated in mdx tibialis anterior and diaphragm
      muscles. Conclusions Our data support the concept that autophagy is impaired in
      the tibialis anterior muscle of mdx mice and that the regulation of autophagy is
      muscle type dependent. Differences between muscle groups should be considered
      during the pre-clinical development of therapeutic strategies addressing muscle
      metabolism. 

PMID- 24292658
TI  - Kinetic studies of the BrO + ClO cross-reaction over the range T = 246-314 K.
AB  - The kinetics of the atmospherically important gas phase radical reaction between
      BrO and ClO have been studied over the temperature range T = 246-314 K by means
      of laser flash photolysis coupled with UV absorption spectroscopy. Charge-coupled
      device (CCD) detection allowed simultaneous monitoring of both free radicals and
      the OClO product using 'differential' spectroscopy, which minimised interference
      from underlying UV absorbing species. In this way, the total rate coefficient for
      BrO + ClO -> products (1) was measured, along with that for the OClO producing
      channel of this process BrO + ClO -> OClO + Br (1c). These reaction rate
      coefficients are described by the Arrhenius expressions: k1/cm(3) molecule(-1) s(
      1) = (2.5 +/- 2.2) * 10(-12) exp[(630 +/- 240)/T] and k(1c)/cm(3) molecule(-1) s(
      1) = (4.6 +/- 3.0) * 10(-12) exp[(280 +/- 180)/T], where errors are 2sigma,
      statistical only. An extensive sensitivity analysis was performed to quantify the
      potential additional systematic uncertainties in this work arising from
      uncertainties in secondary chemistry, absorption cross-sections and precursor
      concentrations. This analysis identified the reactions of initial and secondarily
      generated bromine atoms (specifically Br + O3 and Br + Cl2O) as particularly
      important, along with the reversible combination of ClO with OClO forming Cl2O3.
      Potential uncertainty in this latter process was used to define the lowest
      temperature of the present study. Results from this work indicate larger absolute
      values for k1 and k(1c) than those reported in previous studies, but a weaker
      negative temperature dependence for k(1c) than previously observed, resulting in
      a branching ratio for with a positive temperature dependence, in disagreement
      with previous studies. is the principal source of OClO in the polar stratosphere
      and is commonly used in atmospheric models as an indicator of stratospheric
      bromine chemistry. Thus these measurements might lead to a reinterpretation of
      modelled stratospheric OClO, which has also been suggested by previous
      comparisons of observations with atmospheric model studies.

PMID- 24292659
TI  - A conversation with Thomas Sudhof. Interview by Ushma S. Neill.

PMID- 24292660
TI  - Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype
      targeted drugs.
AB  - Serotonin (5-hydroxytryptamine, or 5-HT) receptors mediate a plethora of
      physiological phenomena in the brain and the periphery. Additionally,
      serotonergic dysfunction has been implicated in nearly every neuropsychiatric
      disorder. The effects of serotonin are mediated by fourteen GPCRs. Both the
      therapeutic actions and side effects of commonly prescribed drugs are frequently
      due to nonspecific actions on various 5-HT receptor subtypes. For more than 20
      years, the search for clinically efficacious drugs that selectively target 5-HT
      receptor subtypes has been only occasionally successful. This review provides an
      overview of 5-HT receptor pharmacology and discusses two recent 5-HT receptor
      subtype-selective drugs, lorcaserin and pimavanserin, which target the 5HT2C and
      5HT2A receptors and provide new treatments for obesity and Parkinson's disease
      psychosis, respectively. 

PMID- 24292661
TI  - Macrophages, fat, and the emergence of immunometabolism.
AB  - Over the last century, our modern concepts and understanding of metabolism and
      immunology have evolved largely in parallel. Notably, during the last decade,
      there has been a sharpened focus on the convergence of metabolism and immune
      function. In part motivated by studies originally published in the JCI, we now
      recognize that the immune system monitors the metabolic state of tissues and
      organisms and responds in kind by modulating metabolic function. The complexity
      of these interactions, both adaptive and pathologic, continues to be studied and
      revealed, with the hope that harnessing the reins that control immune function
      may one day be used for metabolic benefit. 

PMID- 24292666
TI  - Protective effect of phosphatidylcholine on restoration of ethanol-injured
      hepatocytes related with caveolin-1.
AB  - The absorption of phospholipid may improve the fluidity of membrane and enzyme
      activities. Phospholipids also play a role in promoting Caveolae formation and
      membrane synthesis. Caveolin-1 has a significant effect on signaling pathways
      involved in regulating cell proliferation and stress responsiveness. Thus, we can
      speculate that Caveolin-1 could affect the sense of environmental stress. We use
      Chang liver cell line to investigate the ability of Caveolin-1 to modulate the
      cellular response to ethanol injury. Caveolin-1 downregulate cells (Cav-1(-/-))
      were established by stable transfecting with psiRNA-CAV1 plasmids, which were
      more sensitive to toxic effects of ethanol than the untransfected parental cells
      (WT). Releasing of ALT and electric conductivity were changed significantly in
      Cav-1(-/-) cells compared with WT. Caveolin-1 gene silencing could obviously down
      regulate the activities of protein kinase C-alpha (PKC-alpha) and phospho-p42/44
      MAP kinase, indicating cell proliferation and self-repairing abilities were
      inhibited. However, the levels of Caveolin-1 and PKC-alpha were increased by
      phosphatidylcholine administration. The results indicated that the inhibition of
      lipid peroxidation by phosphatidylcholine could lead to the prevention of
      membrane disruption, which closely correlated with the level of Caveolin-1. Since
      the protective effects of phosphatidylcholine against ethanol-induced lipid
      peroxidation might be regulated by phospholipid-PKC-alpha signaling pathway,
      related with Caveolin-1, the potential effects of phosphatidylcholine on
      membranes need to be verified. 

PMID- 24292668
TI  - A novel tool for dynamic cell adhesion studies--the De-Adhesion Number
      Investigator DANI.
AB  - For an optimal implementation of materials, such as, e.g. medical implants in
      living environments, a thorough characterization of cell adhesion, kinetics and
      strength is required, as well as a prerequisite e.g. for bone integration. Here
      we present a miniaturized (~100 MUl) lab-on-a-chip implant hybrid system which
      allows quantification of cell adhesion under dynamic conditions mimicking those
      of physiological relevance. Surface acoustic waves are excited and used on
      optical transparent chips to induce micro acoustic streaming and to create a
      microfluidic shear spectrum ranging from 0 to ~35 s(-1). We demonstrate its
      potential for a time-efficient, dynamic screening test of new implant materials
      using a model of an osseointegration with SAOS-2 cells. The upside-down
      orientation also allows utilization of the micro reactor on non-transparent
      materials like titanium and diamond-like-carbon (DLC). 

PMID- 24292669
TI  - The immigrant paradox: immigrants are less antisocial than native-born Americans.
AB  - PURPOSE: Although recent research on crime and violence among immigrants suggests
      a paradox--where immigrants are more socially disadvantaged yet less likely to
      commit crime--previous research is limited by issues of generalizability and
      assessment of the full depth of antisocial behavior. METHODS: We surmount these
      limitations using data from waves I and II of the National Epidemiologic Survey
      on Alcohol and Related Conditions (NESARC) and compare immigrants (N = 7,320)
      from Asia, Africa, Europe, and Latin America to native-born Americans (N =
      34,622) with respect to violent and nonviolent forms of antisocial behavior.
      RESULTS: After controlling for an extensive array of confounds, results indicate
      that immigrants are significantly less antisocial despite being more likely to
      have lower levels of income, less education, and reside in urban areas. These
      findings hold for immigrants from major regions of the world including Africa,
      Asia, Europe, and Latin America. CONCLUSIONS: This study confirms and extends
      prior research on crime and antisocial behavior, but suggests that it is
      premature however to think of immigrants as a policy intervention for treating
      high crime areas.

PMID- 24292667
TI  - Prediction of aquaporin function by integrating evolutionary and functional
      analyses.
AB  - Aquaporins (AQPs) are a family of channel proteins, which transport water and/or
      small solutes across cell membranes. AQPs are present in Bacteria, Eukarya, and
      Archaea. The classical AQP evolution paradigm explains the inconsistent
      phylogenetic trees by multiple transfer events and emphasizes that the assignment
      of orthologous AQPs is not possible, making it difficult to integrate functional
      information. Recently, a novel phylogenetic framework of eukaryotic AQP evolution
      showed congruence between eukaryotic AQPs and organismal trees identifying 32
      orthologous clusters in plants and animals (Soto et al. Gene 503:165-176, 2012).
      In this article, we discuss in depth the methodological strength, the ability to
      predict functionality and the AQP community perception about the different
      paradigms of AQP evolution. Moreover, we show an updated review of AQPs transport
      functions in association with phylogenetic analyses. Finally, we discuss the
      possible effect of AQP data integration in the understanding of water and solute
      transport in eukaryotic cells. 

PMID- 24292670
TI  - Establishing serological classification tree model in rheumatoid arthritis using
      combination of MALDI-TOF-MS and magnetic beads.
AB  - To establish a serological classification tree model for rheumatoid arthritis
      (RA), protein/peptide profiles of serum were detected by matrix-assisted laser
      desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined
      with weak cationic exchange (WCX) from Cohort 1, including 65 patients with RA
      and 41 healthy controls (HC). The samples were randomly divided into a training
      set and a test set. Twenty-four differentially expressed peaks (P < 0.05) were
      identified in the training set and 4 of them, namely m/z 3,939, 5,906, 8,146, and
      8,569 were chosen to set up our model. This model exhibited a sensitivity of
      100.0% and a specificity of 96.0% for differentiating RA patients from HC. The
      test set reproduced these high levels of sensitivity and specificity, which were
      100.0 and 81.2%, respectively. Cohort 2, which include 228 RA patients, was used
      to further verify the classification efficiency of this model. It came out that
      97.4% of them were classified as RA by this model. In conclusion, MALDI-TOF-MS
      combined with WCX magnetic beads was a powerful method for constructing a
      classification tree model for RA, and the model we established was useful in
      recognizing RA.

PMID- 24292671
TI  - An in vivo RNAi screen identifies SALL1 as a tumor suppressor in human breast
      cancer with a role in CDH1 regulation.
AB  - The gold standard for determining the tumorigenic potential of human cancer cells
      is a xenotransplantation into immunodeficient mice. Higher tumorigenicity of
      cells is associated with earlier tumor onset. Here, we used xenotransplantation
      to assess the tumorigenic potential of human breast cancer cells following RNA
      interference-mediated inhibition of over 5000 genes. We identify 16 candidate
      tumor suppressors, one of which is the zinc-finger transcription factor SALL1.
      Analyzing this particular molecule in more detail, we show that inhibition of
      SALL1 correlates with reduced levels of CDH1, an important contributor to
      epithelial-to-mesenchymal transition. Furthermore, SALL1 expression led to an
      increased migration and more than twice as many cells expressing a cancer stem
      cell signature. Also, SALL1 expression correlates with the survival of breast
      cancer patients. These findings cast new light on a gene that has previously been
      described to be relevant during embryogenesis, but not carcinogenesis. 

PMID- 24292672
TI  - Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is
      associated with tumor grade and overexpression of cyclin D1 protein.
AB  - Human protein arginine N-methyltransferase 2 (PRMT2, HRMT1L1) is a protein that
      belongs to the arginine methyltransferase family, and it has diverse roles in
      transcriptional regulation through different mechanisms depending on its binding
      partners. In this study, we provide evidences for the negative effect of PRMT2 on
      breast cancer cell proliferation in vitro and in vivo. Morever, cyclin D1, one of
      the key modulators of cell cycle, was found to be downregulated by PRMT2, and
      PRMT2 was further shown to suppress the estrogen receptor alpha-binding affinity
      to the activator protein-1 (AP-1) site in cyclin D1 promoter through indirect
      binding with AP-1 site, resulting in the inhibition of cyclin D1 promoter
      activity in MCF-7 cells. Furthermore, a positive correlation between the
      expression of PRMT2 and cyclin D1 was confirmed in the breast cancer tissues by
      using tissue microarray assay. In addition, PRMT2 was found to show a high absent
      percentage in breast caner cell nuclei and the nuclear loss ratio of PRMT2 was
      demonstrated to positively correlate with cyclin D1 expression and the increasing
      tumor grade of invasive ductal carcinoma. Those results offer an essential
      insight into the effect of PRMT2 on breast carcinogenesis, and PRMT2 nuclear loss
      might be an important biological marker for the diagnosis of breast cancer. 

PMID- 24292673
TI  - ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in
      acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is frequently linked to epigenetic abnormalities and
      deregulation of gene transcription, which lead to aberrant cell proliferation and
      accumulation of undifferentiated precursors. ZRF1, a recently characterized
      epigenetic factor involved in transcriptional regulation, is highly overexpressed
      in human AML, but it is not known whether it plays a role in leukemia
      progression. Here, we demonstrate that ZRF1 depletion decreases cell
      proliferation, induces apoptosis and enhances cell differentiation in human AML
      cells. Treatment with retinoic acid (RA), a differentiating agent currently used
      to treat certain AMLs, leads to a functional switch of ZRF1 from a negative
      regulator to an activator of differentiation. At the molecular level, ZRF1
      controls the RA-regulated gene network through its interaction with the RA
      receptor alpha (RARalpha) and its binding to RA target genes. Our genome-wide
      expression study reveals that ZRF1 regulates the transcription of nearly half of
      RA target genes. Consistent with our in vitro observations that ZRF1 regulates
      proliferation, apoptosis, and differentiation, ZRF1 depletion strongly inhibits
      leukemia progression in a xenograft mouse model. Finally, ZRF1 knockdown
      cooperates with RA treatment in leukemia suppression in vivo. Taken together, our
      data reveal that ZRF1 is a key transcriptional regulator in leukemia progression
      and suggest that ZRF1 inhibition could be a novel strategy to be explored for AML
      treatment. 

PMID- 24292674
TI  - PPARgamma E3 ubiquitin ligase regulates MUC1-C oncoprotein stability.
AB  - MUC1-C oncoprotein is associated with colon, breast, ovarian, lung and pancreatic
      cancers. MUC1-C interacts with intracellular proteins to elicit signaling
      cascades that induce cell proliferation and tumor growth. Here we report that
      peroxisome proliferator-activated receptor gamma (PPARgamma), an E3 ubiquitin
      ligase, is an inhibitor of MUC1-C-mediated cell proliferation. PPARgamma does so
      by binding to and inducing MUC1-C proteasome-dependent degradation that was
      independent of PPARgamma transcriptional activity. Lys134 residue was found to be
      critically important for PPARgamma-mediated MUC1-C degradation, as it terminated
      MUC1-C-mediated cell proliferation. These findings demonstrate PPARgamma induces
      MUC1-C ubiquitination and degradation that is critical to terminate MUC1-C
      signaling pathway-elicited cancer. 

PMID- 24292675
TI  - The deubiquitylase Ataxin-3 restricts PTEN transcription in lung cancer cells.
AB  - The phosphatidylinositol-3-kinase (PI3K) pathway is commonly hyperactivated in
      cancer. One mechanism by which this occurs is by silencing of the phosphatase and
      tensin homolog (PTEN), a tumor suppressor and major antagonist of the pathway,
      through genetic, epigenetic or posttranscriptional mechanisms. Here, we used an
      unbiased siRNA screen in non-small-cell lung cancer cells to identify
      deubiquitylases (DUBs) that have an impact on PI3K signaling by regulating the
      abundance of PTEN. We found that PTEN expression was induced by depleting any of
      three members of the Josephin family DUBs: ataxin 3 (ATXN3), ataxin 3-like
      (ATXN3L) and Josephin domain containing 1 (JOSD1). However, this effect is not
      mediated through altered PTEN protein stability. Instead, depletion of each DUB
      increases expression of both the PTEN transcript and its competing endogenous
      RNA, PTENP1. In ATXN3-depleted cells, under conditions of transcriptional
      inhibition, PTEN and PTENP1 mRNAs rapidly decay, suggesting that ATXN3 acts
      primarily by repressing their transcription. Importantly, the PTEN induction
      observed in response to ATXN3 siRNA is sufficient to downregulate Akt
      phosphorylation and hence PI3K signaling. Histone deacetylase inhibitors (HDACi)
      have been suggested as potential mediators of PTEN transcriptional reactivation
      in non-small-cell lung cancer. Although PTEN exhibits a very limited response to
      the broad-spectrum HDACi Vorinostat (SAHA) in A549 cells, we find that
      combination with ATXN3 depletion enhances PTEN induction in an additive manner.
      Similarly, these interventions additively decrease cell viability. Thus, ATXN3
      provides an autonomous, complementary therapeutic target in cancers with
      epigenetic downregulation of PTEN. 

PMID- 24292677
TI  - YGLF motif in the Kaposi sarcoma herpes virus G-protein-coupled receptor adjusts
      NF-kappaB activation and paracrine actions.
AB  - Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) are two pathologies
      associated with KS herpes virus (KSHV/HHV-8) infection. KSHV genome contains
      several oncogenes, among which, the viral G-protein-coupled receptor (vGPCR open
      reading frame 74) has emerged as a major factor in KS pathogenicity. Indeed,
      vGPCR is a constitutively active receptor, whose expression is sufficient to
      drive cell transformation in vitro and tumour development in mice. However,
      neither the role of vGPCR in KSHV-infected B-lymphocytes nor the molecular basis
      for its constitutive activation is well understood. Here, we show that vGPCR
      expression contributes to nuclear factor-kappaB (NF-kappaB)-dependent cellular
      survival in both PEL cells and primary B cells from HIV-negative KS patients. We
      further identified within vGPCR an AP2 consensus binding motif, Y326GLF, that
      directs its localization between the plasma membrane and clathrin-coated
      vesicles. The introduction of a mutation in this site (Y326A) increased NF-kappaB
      activity and proinflammatory cytokines production. This correlated with
      exacerbated morphological rearrangement, migration and proliferation of non
      infected monocytes. Collectively, our work raises the possibility that KSHV
      infected B-lymphocytes use vGPCR to impact ultimately the immune response and
      communication within the tumour microenvironment in KSHV-associated pathologies. 

PMID- 24292676
TI  - Conditional deletion of p53 and Rb in the renin-expressing compartment of the
      pancreas leads to a highly penetrant metastatic pancreatic neuroendocrine
      carcinoma.
AB  - Efforts to model human pancreatic neuroendocrine tumors (PanNETs) in animals have
      been moderately successful, with minimal evidence for glucagonomas or metastatic
      spread. The renin gene, although classically associated with expression in the
      kidney, is also expressed in many other extrarenal tissues including the
      pancreas. To induce tumorigenesis within rennin-specific tissues, floxed alleles
      of p53 and Rb were selectively abrogated using Cre-recombinase driven by the
      renin promoter. The primary neoplasm generated is a highly metastatic islet cell
      carcinoma of the pancreas. Lineage tracing identifies descendants of renin
      expressing cells as pancreatic alpha cells despite a lack of active renin
      expression in the mature pancreas. Both primary and metastatic tumors express
      high levels of glucagon; furthermore, an increased level of glucagon is found in
      the serum, identifying the pancreatic cancer as a functional glucagonoma. This
      new model is highly penetrant and exhibits robust frequency of metastases to the
      lymph nodes and the liver, mimicking human disease, and provides a useful
      platform for better understanding pancreatic endocrine differentiation and
      development, as well as islet cell carcinogenesis. The use of fluorescent
      reporters for lineage tracing of the cells contributing to disease initiation and
      progression provides an unique opportunity to dissect the timeline of disease,
      examining mechanisms of the metastatic process, as well as recovering primary and
      metastatic cells for identifying cooperating mutations that are necessary for
      progression of disease. 

PMID- 24292678
TI  - Restricting direct interaction of CDC37 with HSP90 does not compromise
      chaperoning of client proteins.
AB  - The HSP90 molecular chaperone plays a key role in the maturation, stability and
      activation of its clients, including many oncogenic proteins. Kinases are a
      substantial and important subset of clients requiring the key cochaperone CDC37.
      We sought an improved understanding of protein kinase chaperoning by CDC37 in
      cancer cells. CDC37 overexpression in human colon cancer cells increased CDK4
      protein levels, which was negated upon CDC37 knockdown. Overexpressing CDC37
      increased CDK4 protein half-life and enhanced binding of HSP90 to CDK4,
      consistent with CDC37 promoting kinase loading onto chaperone complexes. Against
      expectation, expression of C-terminus-truncated CDC37 (DeltaC-CDC37) that lacks
      HSP90 binding capacity did not affect kinase client expression or activity;
      moreover, as with wild-type CDC37 overexpression, it augmented CDK4-HSP90 complex
      formation. However, although truncation blocked binding to HSP90 in cells, DeltaC
      CDC37 also showed diminished client protein binding and was relatively unstable.
      CDC37 mutants with single and double point mutations at residues M164 and L205
      showed greatly reduced binding to HSP90, but retained association with client
      kinases. Surprisingly, these mutants phenocopied wild-type CDC37 overexpression
      by increasing CDK4-HSP90 association and CDK4 protein levels in cells.
      Furthermore, expression of the mutants was sufficient to protect kinase clients
      CDK4, CDK6, CRAF and ERBB2 from depletion induced by silencing endogenous CDC37,
      indicating that CDC37's client stabilising function cannot be inactivated by
      substantially reducing its direct interaction with HSP90. However, CDC37 could
      not compensate for loss of HSP90 function, showing that CDC37 and HSP90 have
      their own distinct and non-redundant roles in maintaining kinase clients. Our
      data substantiate the important function of CDC37 in chaperoning protein kinases.
      Furthermore, we demonstrate that CDC37 can stabilise kinase clients by a
      mechanism that is not dependent on a substantial direct interaction between CDC37
      and HSP90, but nevertheless requires HSP90 activity. These results have
      significant implications for therapeutic targeting of CDC37. 

PMID- 24292679
TI  - Mechanism of human PTEN localization revealed by heterologous expression in
      Dictyostelium.
AB  - Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated tumor
      suppressor genes in cancers. PTEN has a central role in phosphatidylinositol
      (3,4,5)-trisphosphate (PIP3) signaling and converts PIP3 to phosphatidylinositol
      (4,5)-bisphosphate at the plasma membrane. Despite its importance, the mechanism
      that mediates membrane localization of PTEN is poorly understood. Here, we
      generated a library that contains green fluorescent protein fused to randomly
      mutated human PTEN and expressed the library in Dictyostelium cells. Using live
      cell imaging, we identified mutations that enhance the association of PTEN with
      the plasma membrane. These mutations were located in four separate regions,
      including the phosphatase catalytic site, the calcium-binding region 3 (CBR3)
      loop, the Calpha2 loop and the C-terminal tail phosphorylation site. The
      phosphatase catalytic site, the CBR3 loop and the Calpha2 loop formed the
      membrane-binding regulatory interface and interacted with the inhibitory
      phosphorylated C-terminal tail. Furthermore, we showed that membrane recruitment
      of PTEN is required for PTEN function in cells. Thus, heterologous expression
      system in Dictyostelium cells provides mechanistic and functional insight into
      membrane localization of PTEN. 

PMID- 24292681
TI  - The role of p21(waf1/cip1) and p27(Kip1) in HDACi-mediated tumor cell death and
      cell cycle arrest in the EMU-myc model of B-cell lymphoma.
AB  - Following the establishment of histone deacetylases (HDACs) as promising
      therapeutic targets for the reversal of aberrant epigenetic states associated
      with cancer, the development of HDAC inhibitors (HDACi) and their underlying
      mechanisms of action has been a significant area of scientific interest. HDACi
      induce diverse biological responses including the inhibition of cell
      proliferation by blocking progression through the G1 or G2/M phases of the cell
      cycle. As a putative tumor-suppressor protein, p21(waf1/cip1) influences cell
      proliferation by inhibiting the activity of cyclin-cyclin-dependent kinase (CDK)
      complexes at the G1/S and G2/M cell cycle checkpoints. HDACi transcriptionally
      activate CDKN1A, and it has been proposed that induction of p21(waf1/cip1) can
      determine if a cell undergoes apoptosis or cell cycle arrest following HDACi
      treatment. In the EMU-myc transgenic mouse model of B-cell lymphoma, knockout of
      cdkn1a had no effect on disease latency, indicating that p21(waf1/cip1) did not
      function as a tumor suppressor in this system. Although HDACi robustly induced
      expression of p21(waf1/cip1) in wild-type EMU-myc lymphomas, deletion of cdkn1a
      did not sensitize the lymphoma cells to HDACi-induced apoptosis and HDACi-induced
      cell cycle arrest still occurred. However, knockdown of cdkn1b in cdkn1a knockout
      lymphomas resulted in defective vorinostat-mediated arrest at G1/S indicating an
      essential role of p27(Kip1) in mediating this biological response to vorinostat.
      These data demonstrate that induction of cdkn1a does not regulate HDACi-mediated
      tumor cell apoptosis and refute the notion that p21(waf1/cip1) is an obligate
      mediator of HDACi-induced cell cycle arrest.

PMID- 24292680
TI  - Elevated levels of FOXA1 facilitate androgen receptor chromatin binding resulting
      in a CRPC-like phenotype.
AB  - Castration-resistant prostate cancer (CRPC) continues to pose a significant
      clinical challenge with new generation second-line hormonal therapies affording
      limited improvement in disease outcome. As the androgen receptor (AR) remains a
      critical driver in CRPC, understanding the determinants of its transcriptional
      activity is important for developing new AR-targeted therapies. FOXA1 is a key
      component of the AR transcriptional complex yet its role in prostate cancer
      progression and the relationship between AR and FOXA1 are not completely
      resolved. It is well established that FOXA1 levels are elevated in advanced
      prostate cancer and metastases. We mimicked these conditions by overexpressing
      FOXA1 in the androgen-responsive LNCaP prostate cancer cell line and observed a
      significant increase in AR genomic binding at novel regions that possess
      increased chromatin accessibility. High levels of FOXA1 resulted in increased
      proliferation at both sub-optimal and high 5alpha-dihydrotestosterone (DHT)
      concentrations. Immunohistochemical staining for FOXA1 in a clinical prostate
      cancer cohort revealed that high FOXA1 expression is associated with shorter time
      to biochemical recurrence after radical prostatectomy (hazard ratio (HR) 5.0, 95%
      confidence interval (CI) 1.2-21.1, P=0.028), positive surgical margins and higher
      stage disease at diagnosis. The gene expression program that results from FOXA1
      overexpression is enriched for PTEN, Wnt and other pathways typically represented
      in CRPC gene signatures. Together, these results suggest that in an androgen
      depleted state, elevated levels of FOXA1 enhance AR binding at genomic regions
      not normally occupied by AR, which in turn facilitates prostate cancer cell
      growth. 

PMID- 24292682
TI  - MiR-106b expression determines the proliferation paradox of TGF-beta in breast
      cancer cells.
AB  - TGF-beta has paradoxical effects on cancer cell proliferation, as it suppresses
      proliferation of normal epithelial and low-invasive cancer cells, but enhances
      that of high-invasive cancer cells. However, how cancer cells acquire the ability
      to evade the tumor-suppressing effects of TGF-beta, yet still take advantage of
      its tumor-promoting effects, remains elusive. Here, we identified miR-106b as a
      molecular switch to determine TGF-beta effects on cell proliferation. TGF-beta1
      enhances the transcription of miR-106b via a promoter independent of its host
      gene MCM7 by activating c-jun. In high-invasive breast cancer cells, miR-106b is
      upregulated by TGF-beta1 at a much higher level than that in normal or low
      invasive cancer cells. Accumulation of miR-106b counterbalances TGF-beta growth
      inhibiting effects by eliminating activated retinoblastoma (RB) and results in
      enhanced proliferation. Furthermore, miR-106b mediates TGF-beta effects on tumor
      growth and metastasis in breast cancer xenografts. In addition, miR-106b
      expression is elevated in higher stage tumors and correlated with tumor
      progression in breast cancer patients. These findings suggest that high level of
      miR-106b induced by TGF-beta determines the tumor-promoting effects of TGF-beta
      in breast cancer. 

PMID- 24292683
TI  - Downregulation of IGFBP2 is associated with resistance to IGF1R therapy in
      rhabdomyosarcoma.
AB  - Agents targeting the insulin-like growth factor-1 receptor (IGF1R) are in
      clinical development, but, despite some initial success of single agents in
      sarcoma, response rates are low with brief durations. Thus, it is important to
      identify markers predictive of response, to understand mechanisms of resistance,
      and to explore combination therapies. In this study, we found that, although
      associated with PAX3-FKHR translocation, increased IGF1R level is an independent
      prognostic marker for worse overall survival, particularly in patients with PAX3
      FKHR-positive rhabdomyosarcoma (RMS). IGF1R antibody-resistant RMS cells were
      generated using an in vivo model. Expression analysis indicated that IGFBP2 is
      both the most affected gene in the insulin-like growth factor (IGF) signaling
      pathway and the most significantly downregulated gene in the resistant lines,
      indicating that there is a strong selection to repress IGFBP2 expression in tumor
      cells resistant to IGF1R antibody. IGFBP2 is inhibitory to IGF1R phosphorylation
      and its signaling. Similar to antibodies to IGF1/2 or IGF2, the addition of
      exogenous IGFBP2 potentiates the activity of IGF1R antibody against the RMS
      cells, and it reverses the resistance to IGF1R antibody. In contrast to IGF1R,
      lower expression of IGFBP2 is associated with poorer overall survival, consistent
      with its inhibitory activity found in this study. Finally, blocking downstream
      Protein kinase B (AKT) activation with Phosphatidylinositide 3-kinases (PI3K)- or
      mammalian target of rapamycin (mTOR)-specific inhibitors significantly sensitized
      the resistant cells to the IGF1R antibody. These findings show that constitutive
      IGFBP2 downregulation may represent a novel mechanism for acquired resistance to
      IGF1R therapeutic antibody in vivo and suggest various drug combinations to
      enhance antibody activity and to overcome resistance. 

PMID- 24292684
TI  - CRL4B promotes tumorigenesis by coordinating with SUV39H1/HP1/DNMT3A in DNA
      methylation-based epigenetic silencing.
AB  - Cullin 4B (CUL4B) is a component of the Cullin4B-Ring E3 ligase complex (CRL4B)
      that functions in proteolysis and is implicated in tumorigenesis. Here, we report
      that CRL4B is associated with histone methyltransferase SUV39H1, heterochromatin
      protein 1 (HP1) and DNA methyltransferases 3A (DNMT3A). We showed that CRL4B,
      through catalyzing H2AK119 monoubiquitination, facilitates H3K9 tri-methylation
      and DNA methylation, two key epigenetic modifications involved in DNA methylation
      based gene silencing. Depletion of CUL4B resulted in loss of not only H2AK119
      monoubiquitination but also H3K9 trimethylation and DNA methylation, leading to
      derepression of a collection of genes, including the tumor suppressor IGFBP3. We
      demonstrated that CUL4B promotes cell proliferation and invasion, which are
      consistent with a tumorigenic phenotype, at least partially by repressing IGFBP3.
      We found that the expression of CUL4B is markedly upregulated in samples of human
      cervical carcinoma and is negatively correlated with the expression of IGFBP3.
      Our experiments unveiled a coordinated action between histone
      ubiquitination/methylation and DNA methylation in transcription repression,
      providing a mechanism for CUL4B in tumorigenesis. 

PMID- 24292685
TI  - Multisite study of an evidence-based practice to reduce seclusion and restraint
      in psychiatric inpatient facilities.
AB  - OBJECTIVE: This federally funded study examined implementation and outcomes of
      the Six Core Strategies for Reduction of Seclusion and Restraint (6CS) in 43
      inpatient psychiatric facilities. METHODS: A prototype Inventory of Seclusion and
      Restraint Reduction Interventions (ISRRI) tracked fidelity over time. Outcome
      measures--seclusion and restraint events as percentages of total inpatient
      population and seclusion and restraint hours as percentages of total inpatient
      hours--conformed to licensed Behavioral Health Performance Measurement System
      specifications. Independent variables were facility and patient characteristics.
      Facilities were classified into five implementation types based on ISRRI scores:
      stabilized (N=28), continued (N=7), decreased (N=5), discontinued (N=1), or never
      implemented (N=2). For the stabilized group, linear modeling and random-effects
      meta-analysis compared the contribution of individual facilities to an overall
      effect. Subgroup analyses explored relationships between facility characteristics
      and outcomes. Dose-effect analysis tested the hypothesis that the stabilized
      group would have more positive outcomes. RESULTS: Overall, the stabilized group
      reduced the percentage secluded by 17% (p=.002), seclusion hours by 19% (p=.001),
      and proportion restrained by 30% (p=.03). The reduction in restraint hours was
      55% but nonsignificant (p=.08). Individual facility effect sizes varied; some
      rates increased for some facilities. The dose-effect hypothesis was supported for
      two outcomes, seclusion hours and percentage restrained. The order of
      implementation group effects in relation to each outcome varied unpredictably.
      CONCLUSIONS: The 6CS was feasible to implement and effective in diverse facility
      types. Fidelity over time was nonlinear and varied among facilities. Further
      research on relationships between facility characteristics, fidelity patterns,
      and outcomes is needed.

PMID- 24292686
TI  - No evidence for a genetic association of IRF4 with systemic lupus erythematosus
      in a Chinese population.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with
      immunological defects caused by abnormal immune regulation and excessive
      production of autoantibodies. Interferon regulatory factor 4 (IRF4) as a
      lymphocyte-restricted member of the IRF family is expressed exclusively in immune
      system cells and is essential for the development of T helper-2 (Th2) cells, IL17
      producing T helper (Th17) cells, and IL9-producing T helper (Th9) cells. Some
      studies have shown that IRF4 is important in the development of autoimmune
      diseases. The role of IRF4 in human SLE has not been extensively studied. This
      article will discuss the relationship between the IRF4 gene polymorphism (single
      nucleotide polymorphism rs872071) and the susceptibility to SLE in a Chinese Han
      population. A case-control study was performed with 663 SLE patients and 658
      healthy controls. The results showed that IRF4 gene polymorphism (rs872071) was
      not significantly different between SLE patients and healthy controls [A/G vs.
      G/G: p = 0.543, odds ratio (OR) = 0.872, 95 % confidence interval (CI) 0.562
      1.355; G vs. A: p = 0.512, OR = 1.058, 95 % CI 0.893-1.254; A/A + A/G vs. G/G: p
      = 0.475, OR = 0.857, 95 % CI 0.562-1.308]. Similarly, in a subgroup analysis of
      clinical manifestation of lupus nephritis (LN), no significant differences were
      found between the non-LN group and the LN group (G/G vs. A/G vs. A/A: chi(2) =
      0.611, p = 0.631; G vs. A: chi(2) = 0.411, p = 0.521).These findings suggest that
      the IRF4 gene polymorphism is not associated with SLE in a Chinese Han
      population; further studies are needed to establish the role of IRF4 in SLE with
      a larger sample size.

PMID- 24292687
TI  - [Remission induction in ANCA-associated vasculitis: Follow-up data of the RAVE
      study].

PMID- 24292689
TI  - A twisted bi-icosahedral Au(25) cluster enclosed by bulky arenethiolates.
AB  - Ligation of 2,6-diphenylbenzenethiol (DppSH) onto Au clusters stabilized by
      poly(N-vinyl-2-pyrrolidone) and subsequent core etching yielded a single cluster
      Au25(SDpp)11. High-energy X-ray diffraction measurement showed that Au25
      constitutes a core in Au25(SDpp)11. We propose a bi-icosahedral Au25 core whose
      22 Au surface atoms are capped directly by 11 bulky arenethiolates. 

PMID- 24292688
TI  - Novel approaches to the post-myocardial infarction/heart failure neural
      remodeling.
AB  - The review aims to discuss the role of nerve growth factor (NGF) as a potential
      novel biomarker in post-myocardial infarction (MI) and in heart failure (HF),
      with a specific focus on neural remodeling and sprouting processes occurring
      after tissue damage. Many experimental data show that MI induces nerve sprouting,
      leading to increased sympathetic outflow and higher risk of ventricular
      arrhythmias and sudden cardiac death. In this framework, cardiac and circulating
      NGF might be an indicator of the innervation process and neural remodeling: it
      dramatically increases after MI, while it declines along with advanced HF and
      ventricular dysfunction. The bimodal behavior of NGF in acute and chronic
      settings leads to the speculation that NGF modulation may be a pharmacological
      target for intervention in different stages of the ischemic heart disease.
      Specifically, a fascinating possibility is to support or to inhibit NGF
      receptors, in order to prevent negative cardiac remodeling after MI and
      consequent ventricular dysfunction. 

PMID- 24292690
TI  - Association of insulin resistance with lower glomerular filtration rate and all
      cause mortality in the Korean elderly population: a community-based prospective
      cohort study.
AB  - Insulin resistance (IR) is a common metabolic disorder in chronic kidney disease
      patients. In the elderly population, it is not clear whether IR is associated
      with lower glomerular filtration rate (GFR) and mortality. Here, we analyzed the
      association between IR and GFR, all-cause mortality (ACM), or cardiovascular
      mortality (CVM) in the elderly population. This was a community-based prospective
      study. Participants were selected by random sampling from those aged >= 65 years
      in Seongnam, a satellite city of Seoul, Korea. A total of 743 participants were
      analyzed. IR was calculated using the homeostasis model assessment of insulin
      resistance (HOMA-IR). The mean age was 76.4 +/- 9.3 years. After multivariate
      analysis, HOMA-IR was negatively associated with GFR as a continuous variable
      (per 10 mL/min/1.73 m(2) increase, beta = -0.10, P = 0.004). Analyzing GFR as a
      categorical variable, HOMA-IR was still higher those with GFR < 60 mL/min/1.73
      m(2) (GFR < 60 vs. 60-89 and >= 90 mL/min/1.73 m(2): 1.3 vs. 1.2 and 1.1,
      respectively; P = 0.025 and 0.019) by covariance analysis. During the follow-up
      period of 62.9 +/- 16.9 months, there were 168 (22.6%) cases of ACM and 47 (6.3%)
      cases of CVM. Those in the third quintile HOMA-IR group showed the lowest ACM
      rate, compared with the other quintiles (P < 0.001). CVM was not significantly
      associated with HOMA-IR. In conclusion, a lower GFR is associated with higher IR
      in the elderly population. Moreover, the lowest or the highest levels of HOMA-IR
      are associated with higher mortality rates. 

PMID- 24292691
TI  - Novel chiral ionic liquids: physicochemical properties and investigation of the
      internal rotameric behaviour in the neat system.
AB  - Optically active S-alkyl-N,N'-bis((S)-1-phenylethyl)thiouronium salts,
      abbreviated as (S)-[C(n)petu]Y (where Y is an anion; n = 1, 2, 3, 4, 6, 8, 10, 12
      or 16), have been prepared and studied by a broad spectrum of analyses. This
      consists of density, viscosity, and conductivity determination, followed by a
      discussion of relevant correlations. Unusual trends depending on the S-alkyl
      chain length were documented for (S)-[C(n)petu][NTf2] series (where [NTf2](-) =
      bis{(trifluoromethyl)sulfonyl}amide), including the viscosity decreasing with
      increasing chain length, and the conductivity showing a maximum between the S
      butyl and the S-hexyl derivative. In addition, a hindered rotamerism of the
      thiouronium cation in dmso-d6 solution was recognised by (1)H and (13)C NMR
      techniques. Thorough analysis of NMR spectra confirmed that the main contribution
      comes from rotation about the partial double C-S bond. For the first time, a neat
      thiouronium ionic liquid system has been subjected to quantitative analysis of
      hindered rotamerism by dynamic NMR coalescence studies, with estimated activation
      energy for rotation of 63.9 +/- 0.4 kJ mol(-1). Finally, the application of (S)
      [C(n)petu]Y salts as chiral discriminating agents for carboxylates by (1)H NMR
      spectroscopy was further investigated, demonstrating the influence of the S-alkyl
      chain length on chiral recognition; (S)-[C2petu][NTf2] ionic liquid with the
      mandelate anion gave the best results.

PMID- 24292692
TI  - Horizontal and vertical distribution of lead, cadmium, and zinc in farmlands
      around a lead-contaminated goldmine in Zamfara, northern Nigeria.
AB  - This study was undertaken to evaluate the vertical and horizontal distribution of
      lead (Pb), cadmium (Cd), and zinc (Zn) in farmlands around a Pb-contaminated
      goldmine. Total concentrations of Pb and Cd recorded were at maximum values of
      2,246.55 and 68.7 mg kg(-1), respectively; these are greater than the threshold
      values for Pb (300 mg kg(-1)) and Cd (3 mg kg(-1)). However, the concentration of
      Zn was within acceptable limits (300 mg kg(-1)). Down the soil profile,
      concentrations of Pb, Cd, and Zn showed two peaks; these were attributed to
      facilitated transport and ground-water enrichment. Incubation of the soil samples
      with glucose indicated low microbial process(es), which could be due to the
      increased levels of Pb and Cd. Factor analysis showed a close association of Pb
      and Cd with the soil-exchange complex with a possibility of these heavy metals
      replacing Ca and other divalent cations in the soil-exchange site. This will,
      however, increase the risk of Pb and Cd leaching and uptake by plants. Although
      the metals were more associated with resistant soil fraction (sand), which also
      indicates their geogenic origin, chemical weathering under the influence of pH
      could release these metals into the soil-exchange site.

PMID- 24292693
TI  - Ion exchangers as adsorbents for removing metals from aquatic media.
AB  - A polyaniline-based composite cation-exchange material was synthesized by way of
      sol-gel method and studied to explore its analytical and environmental
      applications. It was characterized by using instrumental analyses [Fourier
      transform infrared (spectrometer), X-ray, thermogravimetric analysis/differential
      thermal analysis, standard electron microscopy, and transmission electron
      microscopy]. Physicochemical studies, such as ion-exchange capacity, pH
      titrations, and chemical stability, along with effect of eluent concentration and
      elution, were also performed to exploit the ion-exchange capabilities. pH
      titration studies showed that the material presents monofunctional strong cation
      exchange behavior. This nanocomposite material is semicrystalline in nature and
      exhibits improved thermal and chemical stability. The partition coefficient
      studies of different metal ions in the material were performed in demineralised
      water and different surfactant media, and it was found to be selective for Pb(II)
      and Hg(II) ions. To exploit the usefulness of the material as an adsorbent, some
      important quantitative binary separations of metal ions were performed on
      polyaniline Zr(IV) molybdophosphate columns. This composite cation exchanger can
      be applied for the treatment of polluted water to remove heavy metals. 

PMID- 24292694
TI  - Assessment of elemental distribution and heavy metals contamination in phosphate
      deposits: potential health risk assessment of finer-grained size fraction.
AB  - The concentrations and chemical distributions of heavy metals (Cd, Cr, Ni, Zn, U,
      and V) in the Al-Jiza phosphate ores were investigated. Typically, the mean
      concentration values of Cd, Cr, Ni, U, and Zn are 15 +/- 8, 109 +/- 21, 34 +/- 6,
      211 +/- 55, 142 +/- 55, and 161 +/- 57 mg kg(-1), respectively. On the other
      hand, the encountered average concentration values of Cd, Cr, Ni, Zn, U, and V in
      the phosphate dust particles (<0.053) were found to be 22 +/- 5, 179 +/- 5, 67 +/
      11, 441 +/- 14, 225 +/- 58, and 311 +/- 9 mg kg(-1), respectively. The
      contamination factors of U and Cr are greater than 1, indicating that these heavy
      metals could be potentially hazardous, if released to the environment.
      Multivariate statistical analysis allowed the identification of three main
      factors controlling the distribution of these heavy metals and the other chemical
      constituents. The extracted factors are as follows: francolite mineral factor,
      clay minerals factor, and diagenesis factor. Health risk assessments of non
      cancerous effects in finer-grained size fraction that might be caused by
      contamination with the heavy elements have been calculated for both children and
      adults. The risk assessments in case of children for non-cancerous effects showed
      that U has values greater than the safe level of hazard index (HI = 1). In case
      of adults, the value of risk for U is also higher as compared to those of Cd, Ni,
      Cr, and Zn where it lies within the safe range of hazard index (HI < 1). Child
      health risk assessment indicates that children are more vulnerable to
      contaminants from phosphate mining than adults.

PMID- 24292695
TI  - Garden soil and house dust as exposure media for lead uptake in the mining
      village of Stratoni, Greece.
AB  - The relationships between two exposure media, garden soil and house dust, were
      studied for Pb uptake in Stratoni village in northern Greece, an industrial area
      of mining and processing of sulphide ore. Lead data for the two media were
      assessed in terms of total and bioaccessible content, measurement and geochemical
      variability, and mineralogical composition. It was found that total Pb was
      enriched in house dust samples by a factor of 2 on average. Total Pb
      concentration in soil samples had a maximum of 2,040 mg/kg and reached a maximum
      of 7,000 mg/kg in house dust samples. The estimated variability due to
      measurement uncertainty was dominated by the sampling process, and the proportion
      of sampling variance was greater for soil samples, indicating a higher degree of
      Pb heterogeneity in soil on the given spatial scale of sampling strata. Although
      the same general spatial trend was observed for both sampling media with
      decreasing Pb concentration by increasing distance from the ore-processing plant,
      Pb in dust samples displayed the highest concentrations within a 300-600-m zone
      from the ore-processing facility. The significant differences which were observed
      in Pb speciation between the studied media were explained by differences in
      mineralogical composition of outdoor soil and indoor dust. Lead-enriched Fe and
      Mn oxides predominated in soil samples while fine galena grains (<10-20 MUm
      diameter) were the major Pb-bearing phase in dust samples. The integrated
      exposure uptake biokinetic model was used to predict the risk of elevated blood
      lead levels in children of Stratoni. Model prediction indicated an average
      probability of 61 % for blood-Pb to exceed 10 MUg/dl. The results underline the
      importance of house dust in risk assessment and highlight the effect of outdoor
      and indoor conditions on the fate of Pb in the particular environment of
      Stratoni.

PMID- 24292696
TI  - Renal amyloidosis in a patient with X-linked agammaglobulinemia (Bruton's
      disease) and bronchiectasis.
AB  - PURPOSE: We present a patient with Bruton's disease and bronchiectasis who
      developed renal AA amyloidosis. CASE REPORT: A 38 year-old man was diagnosed with
      X-linked agammaglobulinemia (Bruton's disease) when he was 3 years old, and he
      has been treated with parenteral immunoglobulin since then. Eighteen years later,
      he was diagnosed with central pulmonary bronchiectasis by computerized tomography
      (CT). In 2008, he gradually developed anemia, edema of lower limbs, and loss of
      weight. METHOD AND RESULTS: Laboratory studies revealed deterioration of renal
      function, normocytic normochromic anemia and nephrotic range proteinuria.
      Hepatitis B and C and HIV serology were negative. Ultrasound and CT of abdomen
      were normal. A renal biopsy revealed deposits with positive PAS and Congo red
      staining in glomeruli, interstitium, and vessel's walls. Immunohistochemistry
      showed positive staining of the A amyloid. Direct immunofluorescence was positive
      with thioflavin and showed focal and glomerular mesangial IgG deposits,
      suggesting renal AA amyloidosis. For 2 years the patient conducted
      pharmacological treatment and follow-up for the Nephrology department with poor
      prognosis and progression of renal function impairment. In January 2011 he began
      dialysis treatment with improvement, and he is currently on the waiting list for
      renal transplantation. CONCLUSION: We present a patient with Bruton's disease and
      bronchiectasis who developed renal AA amyloidosis a finding rarely reported.

PMID- 24292698
TI  - Genetic diversity and conservation implications of four Cupressus species in
      China as revealed by microsatellite markers.
AB  - Understanding the extent and distribution of genetic diversity is crucial for the
      conservation and management of endangered species. Cupressus chengiana, C.
      duclouxiana, C. gigantea, and C. funebris are four ecologically and economically
      important species in China. We investigated their genetic diversity, population
      structure, and extant effective population size (35 populations, 484 individuals)
      employing six pairs of nuclear microsatellite markers (selected from 53). Their
      genetic diversity is moderate among conifers, and genetic differentiation among
      populations is much lower in C. gigantea than in the other three species; the
      estimated effective population size was largest for C. chengiana, at 1.70, 2.91,
      and 3.91 times the estimates for C. duclouxiana, C. funebris, and C. gigantea,
      respectively. According to Bayesian clustering analysis, the most plausible
      population subdivision scheme within species is two groups in C. chengiana, three
      groups in C. duclouxiana, and a single group for both C. funebris and C.
      gigantea. We propose a conservation strategy for these cypress species. 

PMID- 24292699
TI  - Factors associated with pulmonary recurrence after pulmonary metastasectomy for
      sarcomatous disease.
AB  - PURPOSE: To analyze the factors associated with survival and pulmonary recurrence
      after complete metastasectomy for patients with sarcomatous disease. METHODS:
      Among the 51 patients who underwent complete pulmonary metastasectomy at our
      hospital between January 2002 and November 2010, 30 (58.8 %) suffered pulmonary
      recurrence in an ipsilateral hemithorax. We analyzed the factors affecting
      survival and recurrence after complete metastasectomy. RESULTS: The 51 patients
      who underwent pulmonary metastasectomy comprised 33 male and 18 female patients,
      with a median age of 22 years (range 11-61 years). The median survival was 24
      months. Multivariate analysis revealed recurrence (p = 0.016) and the type of
      tumor (p = 0.024) as independent predictors of survival. Recurrence developed in
      30 (58.8 %) patients. The risk of recurrence was higher in patients with a DFI
      <12 months and >1 metastasis resected during the initial metastasectomy.
      CONCLUSIONS: Based on the findings of our analysis, patients with a DFI <12
      months and >1 metastases resected during initial surgery have a higher risk of
      recurrence. We recommend postoperative follow-up at frequent intervals and
      reconsideration of oncological treatment after complete resection.

PMID- 24292697
TI  - Ocular involvement in primary immunodeficiency diseases.
AB  - Primary immunodeficiency diseases (PID) are a group of inherited disorders
      characterized by recurrent infections, and in many cases autoimmunity and
      malignancies. A number of PID patients suffer from a variety of ocular
      manifestations. Although these associated ocular features are not common,
      awareness combined with better understanding of the contributing mechanisms will
      allow prompt diagnosis and specific treatment, leading to reduction or prevention
      of serious visual morbidities. 

PMID- 24292700
TI  - Increased sensitivity to glucose starvation correlates with downregulation of
      glycogen phosphorylase isoform PYGB in tumor cell lines resistant to 2-deoxy-D
      glucose.
AB  - BACKGROUND: As tumors evolve, they upregulate glucose metabolism while also
      encountering intermittent periods of glucose deprivation. Here, we investigate
      mechanisms by which pancreatic cancer cells respond to therapeutic (2-deoxy-D
      glucose, 2-DG) and physiologic (glucose starvation, GS) forms of glucose
      restriction. METHODS: From a tumor cell line (1420) that is unusually sensitive
      to 2-DG under normoxia, low (14DG2)- and high (14DG5)-dose resistant cell lines
      were selected and used to probe the metabolic pathways involved with their
      response to different forms of glucose deprivation. RESULTS: Muted induction of
      the unfolded protein response was found to correlate with resistance to 2-DG.
      Additionally, 14DG2 displayed reduced 2-DG uptake, while 14DG5 was cross
      resistant to tunicamycin, suggesting it has enhanced ability to manage
      glycosylation defects. Conversely, 2-DG-resistant cell lines were more sensitive
      than their parental cell line to GS, which coincided with lowered levels of
      glycogen phosphorylase (PYGB) and reduced breakdown of glycogen to glucose in the
      2-DG-resistant cell lines. Moreover, by inhibiting PYGB in the parental cell
      line, sensitivity to GS was increased. CONCLUSIONS: Overall, the data demonstrate
      that the manner in which glucose is restricted in tumor cells, i.e., therapeutic
      or physiologic, leads to differential biological responses involving distinct
      glucose metabolic pathways. Moreover, in evolving tumors where glucose
      restriction occurs, the identification of PYGB as a metabolic target may have
      clinical application.

PMID- 24292701
TI  - Usability of a gravity- and tilt-compensated sensor with data logging function to
      measure posturing compliance in patients after macular hole surgery: a pilot
      study.
AB  - BACKGROUND: To investigate the use of a small gravity- and tilt-compensated, head
      fixed sensor with data-logging function to measure compliance and head posture of
      patients after macular hole surgery based on the recommendation of a face-down
      position. Main outcome measures were the median inclination, the times with
      correct or incorrect head position and the acceptance/annoyance of a data-logging
      device. METHODS: A small battery-driven electronic sensor device with gravity and
      tilt compensations was placed within a plastic box and fixed on a patient's head
      with a headband. Face-down position data were logged every half second for 24 h
      after macular hole surgery and were stored on a memory card. RESULTS: Thirteen
      patients were involved (seven females, six males, median age, 68 years, range, 50
      75 years), two cases with early dropout. Ten of 11 datasets could be evaluated
      showing a complete data record file. The average percentage for face-down >45
      degrees  was 18% within 24 h and 17% in the daytime. The median inclination was 
      6.7 degrees  (min: -89.7 degrees  max: 90 degrees ). The sensor system was well
      tolerated and disturbance was rated low by all ten patients. CONCLUSIONS: While
      the patients' face-down posture considerably varied over time in extent and
      continuity, the assessment might lead to optimizing the patients' compliance with
      the optimal position. Results showed an excellent acceptance of the motion
      sensor.

PMID- 24292702
TI  - Can optical coherence tomography replace fluorescein angiography in detection of
      ischemic diabetic maculopathy?
AB  - BACKGROUND: We studied the association between (1) the retinal thickness, volume
      and structure assessed by optical coherence tomography (OCT), and (2) vascular
      changes around the fovea in FA to define the role of these methods in the
      detection of ischemic diabetic maculopathy. METHODS: This retrospective
      observational study included 51 eyes of 51 patients with severe non-proliferative
      and proliferative diabetic retinopathy, considering that they present advanced
      ischemic retinal changes. Based on the clinical examination and presence of
      leakage on FA, patients with clinically significant macular edema were excluded.
      On FA, foveal avascular zone (FAZ) corresponds to capillary loss and reflects
      ischemic processes. Its outline and size were assessed according to the ETDRS
      standards. Patients were divided in two groups according to the severity of
      damage of the FAZ outline: <= grade 2 (n = 28) and >= grade 3 (n = 23). As we
      expected ischemia-related damage, SD-OCT images were evaluated for retinal
      structure, volume, total thickness with division into the outer and inner retina
      (to assess the influence of two, non-overlapping blood sources) and ganglion cell
      layer thickness. RESULTS: The comparisons revealed that at least currently with
      described methods: 1. There is no significant association between FAZ outline and
      retinal volume, total thickness, and thickness of the outer and inner retina and
      ganglion cell layer. 2. There is no significant association between FAZ outline
      and following retinal structure characteristics: continuity of the external
      limiting membrane and inner segment/outer segment junction, and identification of
      the inner/outer retina boundary. 3. The identification of ganglion cell layer
      boundaries was significantly more difficult in more advanced FAZ outline grades.
      4. FAZ size is not correlated with the retinal thickness and volume. CONCLUSIONS:
      In patients with severe non-proliferative and proliferative diabetic retinopathy,
      it is not possible to predict FAZ outline/size based solely on the measurements
      assessing volume and thickness or retinal structure evaluation on OCT.
      Consequently, at present OCT cannot replace FA in the detection of ischemic
      diabetic maculopathy.

PMID- 24292704
TI  - Direct observation of carbon nanostructure growth at liquid-solid interfaces.
AB  - Our TEM observation revealed that in a carbon-Pt3Co system, amorphous carbon
      first crystallized into nanoclusters at step-edges on melting Pt3Co surfaces
      before merging into graphene layers through a kinetic restructuring via oriented
      attachment, leading to the final formation of few-layered graphene
      nanostructures. The result obtained from density-functional theory calculations
      further suggested that Co atoms rather than Pt atoms acted as initial nucleation
      centers. 

PMID- 24292703
TI  - Effects of arteriolar constriction on retinal gene expression and Muller cell
      responses in a rat model of branch retinal vein occlusion.
AB  - BACKGROUND: To investigate the effect of induced arteriolar constriction (AC) on
      alterations in gene expression of factors implicated in the development of edema
      in branch retinal vein occlusion (BRVO). METHODS: In Brown-Norway rats, BRVO was
      induced by laser photocoagulation of the veins in one half of the retina. AC of
      the afferent arterioles was performed 30 min later. We then determined the
      expression of Vegfa, Vegfb, Pedf, Kir4.1, Aqp4, Aqp1, Il1beta, and Il6 with real
      time polymerase chain reaction (RT-PCR) in the neuroretina and retinal pigment
      epithelium (RPE) after 1, 3, and 7 days. Immunostaining against GFAP, aquaporin
      (AQP)-4, and Kir4.1 was performed on days 1 and 3. RESULTS: BRVO resulted in
      transient upregulation of Vegfa in the neuroretina on day 1. The expressions of
      Kir4.1, AQP4, and AQP1 were downregulated, and Il1beta and Il6 were strongly
      upregulated, on days 1 and 3. The retinal distribution of GFAP and AQP4 proteins
      remained unaltered, while the Kir4.1 protein displayed redistribution from
      polarized to uniform retinal distribution. AC accelerated the restoration of
      downregulated Kir4.1, Aqp4, and Aqp1 in the RPE, of Kir4.1 in the neuroretina,
      and of upregulated Il6 in the neuroretina. AC did not influence the gliotic
      alterations of Muller cells and the redistribution of the Kir4.1 protein.
      CONCLUSION: Constriction of the afferent artery in the BRVO region accelerated
      the restoration of potassium channels and Il6. These alterations may contribute
      to faster resorption of retinal edema, and may decrease the level of
      inflammation.

PMID- 24292705
TI  - A digital microfluidic electrochemical immunoassay.
AB  - Digital microfluidics (DMF) has emerged as a popular format for implementing
      quantitative immunoassays for diagnostic biomarkers. All previous reports of such
      assays have relied on optical detection; here, we introduce the first digital
      microfluidic immunoassay relying on electrochemical detection. In this system, an
      indium tin oxide (ITO) based DMF top plate was modified to include gold sensing
      electrodes and silver counter/pseudoreference electrodes suitable for in-line
      amperometric measurements. A thyroid stimulating hormone (TSH) immunoassay
      procedure was developed relying on magnetic microparticles conjugated with
      primary antibody (Ab1). Antigen molecules are captured followed by capture of a
      secondary antibody (Ab2) conjugated with horseradish peroxidase enzyme (HRP). HRP
      catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) which can be
      detected amperometrically. The limit of detection of the technique (2.4 MUIU mL(
      1)) is compatible with clinical applications; moreover, the simplicity and the
      small size of the detector suggest utility in the future for portable analysis. 

PMID- 24292706
TI  - IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients.
AB  - High-dose (HD) IL-2 therapy in patients with cancer increases the general
      population of Tregs, which are positive for CD4, CD25, and the Treg-specific
      marker Foxp3. It is unknown whether specific subsets of Tregs are activated and
      expanded during HD IL-2 therapy or whether activation of any particular Treg
      subset correlates with clinical outcome. Here, we evaluated Treg population
      subsets that were induced in patients with melanoma following HD IL-2 therapy. We
      identified a Treg population that was positive for CD4, CD25, Foxp3, and the
      inducible T cell costimulator (ICOS). This Treg population increased more than
      any other lymphocyte subset during HD IL-2 therapy and had an activated Treg
      phenotype, as indicated by high levels of CD39, CD73, and TGF-beta. ICOS(+) Tregs
      were the most proliferative lymphocyte population in the blood after IL-2
      therapy. Patients with melanoma with enhanced expansion of ICOS(+) Tregs in blood
      following the first cycle of HD IL-2 therapy had worse clinical outcomes than
      patients with fewer ICOS(+) Tregs. However, there was no difference in total Treg
      expansion between HD IL-2 responders and nonresponders. These data suggest that
      increased expansion of the ICOS(+) Treg population following the first cycle of
      HD IL-2 therapy may be predictive of clinical outcome.

PMID- 24292707
TI  - Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK
      3beta.
AB  - Cardiac resynchronization therapy (CRT), the application of biventricular
      stimulation to correct discoordinate contraction, is the only heart failure
      treatment that enhances acute and chronic systolic function, increases cardiac
      work, and reduces mortality. Resting myocyte function also increases after CRT
      despite only modest improvement in calcium transients, suggesting that CRT may
      enhance myofilament calcium responsiveness. To test this hypothesis, we examined
      adult dogs subjected to tachypacing-induced heart failure for 6 weeks, concurrent
      with ventricular dyssynchrony (HF(dys)) or CRT. Myofilament force-calcium
      relationships were measured in skinned trabeculae and/or myocytes. Compared with
      control, maximal calcium-activated force and calcium sensitivity declined
      globally in HF(dys); however, CRT restored both. Phosphatase PP1 induced calcium
      desensitization in control and CRT-treated cells, while HF(dys) cells were
      unaffected, implying that CRT enhances myofilament phosphorylation. Proteomics
      revealed phosphorylation sites on Z-disk and M-band proteins, which were
      predicted to be targets of glycogen synthase kinase-3beta (GSK-3beta). We found
      that GSK-3beta was deactivated in HF(dys) and reactivated by CRT. Mass
      spectrometry of myofilament proteins from HF(dys) animals incubated with GSK
      3beta confirmed GSK-3beta-dependent phosphorylation at many of the same sites
      observed with CRT. GSK-3beta restored calcium sensitivity in HF(dys), but did not
      affect control or CRT cells. These data indicate that CRT improves calcium
      responsiveness of myofilaments following HF(dys) through GSK-3beta reactivation,
      identifying a therapeutic approach to enhancing contractile function

PMID- 24292708
TI  - Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity.
AB  - Recent studies have underscored the importance of memory T cells in mediating
      protective immunity against pathogens and cancer. Pharmacological inhibition of
      regulators that mediate T cell differentiation promotes the differentiation of
      activated CD8(+) T cells into memory cells. Nonetheless, pharmacological agents
      have broad targets and can induce undesirable immunosuppressive effects. Here, we
      tested the hypothesis that aptamer-targeted siRNA inhibition of mTOR complex 1
      (mTORC1) function in CD8(+) T cells can enhance their differentiation into memory
      T cells and potentiate antitumor immunity more effectively than the pharmacologic
      inhibitor rapamycin. To specifically target activated cells, we conjugated an
      siRNA targeting the mTORC1 component raptor to an aptamer that binds 4-1BB, a
      costimulatory molecule that is expressed on CD8(+) T cells following TCR
      stimulation. We found that systemic administration of the 4-1BB aptamer-raptor
      siRNA to mice downregulated mTORC1 activity in the majority of CD8(+) T cells,
      leading to the generation of a potent memory response that exhibited cytotoxic
      effector functions and enhanced vaccine-induced protective immunity in tumor
      bearing mice. In contrast, while treatment with the general mTORC1 inhibitor
      rapamycin also enhanced antigen-activated CD8(+) T cell persistence, the
      cytotoxic effector functions of the reactivated memory cells were reduced and the
      alloreactivity of DCs was diminished. Consistent with the immunological findings,
      mice treated with rapamycin, but not with 4-1BB aptamer-raptor siRNA, failed to
      reject a subsequent tumor challenge.

PMID- 24292709
TI  - Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent
      Plasmodium falciparum infection.
AB  - Malaria, which is the result of Plasmodium falciparum infection, is a global
      health threat that resulted in 655,000 deaths and 216 million clinical cases in
      2010 alone. Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01
      (RTS,S) in children has demonstrated modest efficacy against clinical and severe
      malaria. RTS,S targets the pre-erythrocytic phase of the disease and induces high
      antibody titers against the P. falciparum circumsporozoite protein (CSP) and a
      moderate CD4(+) T cell response. The individual contribution of these adaptive
      immune responses to protection from infection remains unknown. Here, we found
      that prophylactic administration of anti-CSP mAbs derived from an RTS,S
      vaccinated recipient fully protected mice with humanized livers from i.v.- and
      mosquito bite-delivered P. falciparum sporozoite challenge. Titers of anti-CSP
      that conveyed full protection were within the range observed in human RTS,S
      vaccine recipients. Increasing anti-CSP titers resulted in a dose-dependent
      reduction of the liver parasite burden. These data indicate that RTS,S-induced
      antibodies are protective and provide sterilizing immunity against P. falciparum
      infection when reaching or exceeding a critical plasma concentration.

PMID- 24292710
TI  - Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation
      throughout life.
AB  - Mammals transport blood through a high-pressure, closed vascular network and
      lymph through a low-pressure, open vascular network. These vascular networks
      connect at the lymphovenous (LV) junction, where lymph drains into blood and an
      LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we
      describe an essential role for platelets in preventing blood from entering the
      lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates
      platelets in response to lymphatic endothelial cells, resulted in backfilling of
      the lymphatic network with blood from the thoracic duct (TD) in both neonatal and
      mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in
      the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice
      lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus
      formation limits LV backflow under conditions of impaired valve function.
      Examination of mice lacking integrin-mediated platelet aggregation indicated that
      platelet aggregation stabilizes thrombi that form in the lymphatic vascular
      environment to prevent retrograde blood flow. Collectively, these studies unveil
      a newly recognized form of hemostasis that functions with the LVV to safeguard
      the lymphatic vascular network throughout life.

PMID- 24292711
TI  - Sprouty-2 regulates HIV-specific T cell polyfunctionality.
AB  - The ability of individual T cells to perform multiple effector functions is
      crucial for protective immunity against viruses and cancer. This
      polyfunctionality is frequently lost during chronic infections; however, the
      molecular mechanisms driving T cell polyfunctionality are poorly understood. We
      found that human T cells stimulated by a high concentration of antigen lacked
      polyfunctionality and expressed a transcription profile similar to that of
      exhausted T cells. One specific pathway implicated by the transcription profile
      in control of T cell polyfunctionality was the MAPK/ERK pathway. This pathway was
      altered in response to different antigen concentrations, and polyfunctionality
      correlated with upregulation of phosphorylated ERK. T cells that were stimulated
      with a high concentration of antigen upregulated sprouty-2 (SPRY2), a negative
      regulator of the MAPK/ERK pathway. The clinical relevance of SPRY2 was confirmed
      by examining SPRY2 expression in HIV-specific T cells, where high levels of SPRY2
      were seen in HIV-specific T cells and inhibition of SPRY2 expression enhanced the
      HIV-specific polyfunctional response independently of the PD-1 pathway. Our
      findings indicate that increased SPRY2 expression during chronic viral infection
      reduces T cell polyfunctionality and identify SPRY2 as a potential target for
      immunotherapy.

PMID- 24292712
TI  - TTC7A mutations disrupt intestinal epithelial apicobasal polarity.
AB  - Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is
      sometimes associated with a combined immunodeficiency (CID), leading to increased
      susceptibility to infections. The factors underlying this rare disease are poorly
      understood. We characterized the immunological and intestinal features of 6
      unrelated MIA-CID patients. All patients displayed a profound, generalized
      lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was
      hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients
      also had profound disruption of the epithelial barrier along the entire
      gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we
      identified 10 mutations in tetratricopeptide repeat domain-7A (TTC7A), all of
      which potentially abrogate TTC7A expression. Intestinal organoid cultures from
      patient biopsies displayed an inversion of apicobasal polarity of the epithelial
      cells that was normalized by pharmacological inhibition of Rho kinase. Our data
      indicate that TTC7A deficiency results in increased Rho kinase activity, which
      disrupts polarity, growth, and differentiation of intestinal epithelial cells,
      and which impairs immune cell homeostasis, thereby promoting MIA-CID development.

PMID- 24292713
TI  - Targeting SOD1 reduces experimental non-small-cell lung cancer.
AB  - Approximately 85% of lung cancers are non-small-cell lung cancers (NSCLCs), which
      are often diagnosed at an advanced stage and associated with poor prognosis.
      Currently, there are very few therapies available for NSCLCs due to the
      recalcitrant nature of this cancer. Mutations that activate the small GTPase KRAS
      are found in 20% to 30% of NSCLCs. Here, we report that inhibition of superoxide
      dismutase 1 (SOD1) by the small molecule ATN-224 induced cell death in various
      NSCLC cells, including those harboring KRAS mutations. ATN-224-dependent SOD1
      inhibition increased superoxide, which diminished enzyme activity of the
      antioxidant glutathione peroxidase, leading to an increase in intracellular
      hydrogen peroxide (H(2)O(2)) levels. We found that ATN-224-induced cell death was
      mediated through H(2)O(2)-dependent activation of P38 MAPK and that P38
      activation led to a decrease in the antiapoptotic factor MCL1, which is often
      upregulated in NSCLC. Treatment with both ATN-224 and ABT-263, an inhibitor of
      the apoptosis regulators BCL2/BCLXL, augmented cell death. Furthermore, we
      demonstrate that ATN-224 reduced tumor burden in a mouse model of NSCLC. Our
      results indicate that antioxidant inhibition by ATN-224 has potential clinical
      applications as a single agent, or in combination with other drugs, for the
      treatment of patients with various forms of NSCLC, including KRAS-driven cancers.

PMID- 24292714
TI  - Gender differences in the mental health of single parents: New Zealand evidence
      from a household panel survey.
AB  - BACKGROUND: In many countries single parents report poorer mental health than
      partnered parents. This study investigates whether there are gender differences
      in the mental health of single parents in New Zealand (and whether any gender
      difference varies with that among partnered parents), and examines key social and
      demographic mediators that may account for this difference. METHODS: We used data
      on 905 single parents and 4,860 partnered parents from a New Zealand household
      panel survey that included the Kessler-10 measure of psychological distress.
      Linear regression analyses were used to investigate both interactions of gender
      and parental status, and confounding or mediation by other covariates. RESULTS:
      High/very high levels of psychological distress were reported by 15.7 % of single
      mothers and 9.1 % of single fathers, and 6.1 % of partnered mothers and 4.1 % of
      partnered fathers. In an Ordinary Least Squares regression of continuous K10
      scores on gender, parental status and the interaction of both (plus adjustment
      for ethnicity, number of children and age), female single parents had a 1.46
      higher K10 score than male single parents (95 % CI 0.48-2.44; 1.46). This
      difference was 0.98 (95 % CI -0.04 to 1.99) points greater than the gender
      difference among partnered parents. After controlling for further confounding or
      mediating covariates (educational level, labour force status and socioeconomic
      deprivation) both the gender difference among single parents (0.38, -0.56 to
      1.31) and the interaction of gender and parental status (0.28 greater gender
      difference among single parents, -0.69 to 1.65) greatly reduced in magnitude and
      became non-significant, mainly due to adjustment for individual socioeconomic
      deprivation. CONCLUSION: The poorer mental health of single parents remains an
      important epidemiological phenomenon. Although research has produced mixed
      findings of the nature of gender differences in the mental health of single
      parents, our research adds to the increasing evidence that it is single mothers
      who have worse mental health. Our findings on the potential explanations of the
      gender difference in sole parent mental health suggest that socioeconomic
      deprivation is a key contributor.

PMID- 24292715
TI  - Napyradiomycins CNQ525.510B and A80915C target the Hsp90 paralogue Grp94.
AB  - The intracellular localization and target of the napyradiomycin congeners
      CNQ525.510B and A80815C were explored using an immunoaffinity fluorescence (IAF)
      approach. Semi-synthetic methods were used to prepare probes from napyradiomycin
      CNQ525.510B and derivative A80815C. The results of confocal microscopy indicated
      that probes from both natural products localized predominantly within the
      endoplasmic reticulum (ER) of HCT-116 human colon carcinoma cells. Parallel
      immunoaffinity precipitation efforts using a monoclonal antibody designed against
      the IAF tag, resulted in the isolation of an Hsp90 family member. This protein
      was identified as human Grp94 (hGrp94), by its specific mass spectral signature.
      This observation was validated by Western blot analyses and by the result of an
      in vitro Grp94 binding assay. The fact that the napyradiomycins CNQ525.510B and
      A80815C bind to hGrp94, and their associated probes localize within the ER,
      suggest the use of these materials as molecular probes for monitoring ER-based
      chaperone function. 

PMID- 24292716
TI  - Responses to nitrogen pulses and growth under low nitrogen availability in
      invasive and native tree species with differing successional status.
AB  - Invasive species are frequently found in recently disturbed sites. To examine how
      these disturbance-dependent invasive species exploit resource pulses resulting
      from disturbance, twelve physiological and morphological traits, including age
      dependent responsiveness in leaf traits to nitrogen pulse, were compared between
      Bischofia javanica, an invasive tree species in Ogasawara islands, and three
      native Ogasawara species, each having a different successional status. When
      exposed to a nitrogen pulse, invasive B. javanica showed higher increases in
      photosynthetic capacity, leaf area, epidermal cell number and cell size in leaves
      of broad age classes, and root nitrogen absorption ability than two native mid
      /late or late-successional species, but showed no particular superiority to a
      native pioneer species in these responses. Under low nitrogen, however, it showed
      the largest relative growth rate among the four species, while the native pioneer
      showed the lowest growth. From these results, we concluded that the combination
      of moderately high responsiveness to resource pulses and the ability to maintain
      steady growth under resource limitations may give B. javanica a competitive
      advantage over a series of native species with different successional status from
      early to late-successional stages. 

PMID- 24292718
TI  - The peculiarities of the SDF-1/CXCL12 system: in some cells, CXCR4 and CXCR7 sing
      solos, in others, they sing duets.
AB  - The chemokine SDF-1/CXCL12 induces and modulates major steps of ontogenesis,
      regeneration and tumorigenesis. Depending on the organ or tissue, CXCL12 serves
      as a proliferation or cell survival factor, influences differentiation, induces
      adhesion and/or regulates cell migration. These functions are mediated by the two
      chemokine receptors, CXCR4 and CXCR7. Whereas CXCR4 is still viewed as the sole G
      protein-activating and, hence, signaling receptor for CXCL12, CXCR7 is regarded
      as a non-classic scavenging or decoy receptor that modulates the function of
      CXCR4. However, this view might be too limited, since evidence has accumulated
      favoring a cell-type-specific mode of CXCL12 signaling. In addition to the
      "classic" CXCL12 signaling mode via CXCR4, CXCR4 and CXCR7 have to form a
      receptor unit for successful CXCL12 signaling in some cells. Moreover, examples
      exist whereby CXCL12 receptors split functions or switch roles, such that CXCR7
      (instead of CXCR4) mediates signal transduction. The obvious lack of a universal
      mode of CXCL12 signaling urges a re-evaluation of the role of this chemokine in
      development, health and disease. This review depicts the exceptional
      characteristics of CXCL12-induced signal transduction in various cells and
      organs, points out remaining controversies and mentions consequences for
      therapeutic interventions. 

PMID- 24292719
TI  - Effects of insulin on norepinephrine- and acetylcholine-induced membrane currents
      of pinealocytes from healthy Wistar and type 2 diabetic GK rats.
AB  - The neurohormone melatonin is synthesized by the pineal gland under the
      stimulation of norepinephrine (NE). Its synthesis is inhibited by acetylcholine
      (ACh) and by insulin. Type 2 diabetic Goto Kakizaki (GK) rats have higher insulin
      and lower melatonin plasma levels than healthy Wistar rats. We investigate
      membrane potentials and currents of isolated pinealocytes in both rat strains and
      the influence of NE, ACh and insulin by using the perforated patch whole cell
      clamp technique. Pinealocyte membranes displayed a high resting Na(+)
      conductance. Stimulation with NE further increased this Na(+) conductance, which
      led to a slight depolarization in unclamped cells. The amplitude of the NE-evoked
      current was similar in both rat strains but the current fraction carried by Na(+)
      was stronger in GK rats. Stimulation with ACh induced a transient inward current
      and depolarization. These effects were much more pronounced in the pinealocytes
      of GK rats. The NE-induced current, the ACh-induced current and the membrane
      depolarization were reduced by pre-administration of insulin in Wistar
      pinealocytes. Our results provide the first electrophysiological evidence for the
      modulation, by insulin, of the effects of NE and ACh in pinealocytes of normal
      rats. The pinealocytes of type 2 diabetic rats were not responsive to insulin.
      This might explain the reported correlation between the decreased insulin
      receptor mRNA transcript levels in GK rat pinealocytes and the lack of effect of
      insulin on ion channels in their cell membranes. 

PMID- 24292720
TI  - Osteoblast ontogeny and implications for bone pathology: an overview.
AB  - Osteoblasts are specialized mesenchyme-derived cells accountable for bone
      synthesis, remodelling and healing. Differentiation of osteoblasts from
      mesenchymal stem cells (MSC) towards osteocytes is a multi-step process strictly
      controlled by various genes, transcription factors and signalling proteins. The
      aim of this review is to provide an update on the nature of bone-forming
      osteoblastic cells, highlighting recent data on MSC-osteoblast-osteocyte
      transformation from a molecular perspective and to discuss osteoblast
      malfunctions in various bone diseases. We present here the consecutive stages
      occurring in the differentiation of osteoblasts from MSC, the transcription
      factors involved and the role of miRNAs in the process. Recent data concerning
      the pathogenic mechanisms underlying the loss of bone mass and architecture
      caused by malfunctions in the synthetic activity and metabolism of osteoblasts in
      osteoporosis, osteogenesis imperfecta, osteoarthritis and rheumatoid arthritis
      are discussed. The newly acquired knowledge of the ontogeny of osteoblasts will
      assist in unravelling the abnormalities taking place during their differentiation
      and will facilitate the prevention and/or treatment of bone diseases by therapy
      directed against altered molecules and mechanisms. 

PMID- 24292722
TI  - Palladium-catalyzed intermolecular [3 + 2] carbocyclization of alkynols and
      propiolates: an efficient entry to halo-cyclopentadienes.
AB  - A novel and efficient Pd-catalyzed intermolecular [3 + 2] carbocyclization of
      alkynols and electron-deficient alkynes for the synthesis of halo
      cyclopentadienes (Cps) has been developed. The present protocol employs simple
      propargyl alcohols as the C3 group to participate in the cyclization reaction,
      providing a highly convenient and atom-economical entry to the halo
      cyclopentadiene framework. 

PMID- 24292723
TI  - Theoretical study on the peroxyl radicals scavenging activity of esculetin and
      its regeneration in aqueous solution.
AB  - The study of the OOH, OOCH3 and OOCHCH2 radicals scavenging processes by
      esculetin (ES) was carried out in aqueous and lipid media, using the density
      functional theory. Three reaction mechanisms were considered: single electron
      transfer (SET), hydrogen transfer (HT) and radical adduct formation (RAF). Rate
      constants and branching ratios for the different paths are reported. It was found
      that in lipid media the main mechanism of reaction is HT, while in aqueous
      solution it depends on the predominant acid-base form of esculetin. HT was found
      to be the main mechanism involved in the free radical scavenging activity of
      neutral esculetin (H2ES), while for anionic esculetin (HES(-)) the relative
      importance of the different mechanisms changes with the reacting radical. Based
      on the calculated rate constants, it is proposed that esculetin has moderate
      peroxyl scavenging activity in lipid media while in aqueous solution, at
      physiological pH, it is excellent for that purpose. In addition, the possible
      regeneration of ES, after scavenging the first radical, was investigated in
      aqueous solution, at physiological pH. It was found that regeneration is very
      likely to occur, which suggests that this compound has the ability to scavenge
      several radical equivalents (two per cycle), under such conditions. 

PMID- 24292725
TI  - Silicon/copper dome-patterned electrodes for high-performance hybrid
      supercapacitors.
AB  - This study proposes a method for manufacturing high-performance electrode
      materials in which controlling the shape of the current collector and electrode
      material for a Li-ion capacitor (LIC). In particular, the proposed LIC
      manufacturing method maintains the high voltage of a cell by using a microdome
      patterned electrode material, allowing for reversible reactions between the Li
      ion and the active material for an extended period of time. As a result, the LICs
      exhibit initial capacities of approximately 42 F g-1, even at 60 A g-1. The LICs
      also exhibit good cycle performance up to approximately 15,000 cycles. In
      addition, these advancements allow for a considerably higher energy density than
      other existing capacitor systems. The energy density of the proposed LICs is
      approximately nine, two, and 1.5 times higher than those of the electrochemical
      double layer capacitor (EDLC), AC/LiMn2O4 hybrid capacitor, and intrinsic Si/AC
      LIC, respectively.

PMID- 24292724
TI  - Positive correlation of STAT1 and miR-146a with anemia in patients with systemic
      lupus erythematosus.
AB  - PURPOSE: Anemia is one of the most common hematological manifestations in SLE
      patients, occurring in about 50% of active cases. STAT1 is a critical signaling
      molecule required for the production of type-1 interferon (I-IFN), CCL2, and
      CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been
      described to be involved in anemia in animal models. The aim of this study is to
      analyze how these components are involved in SLE-associated anemia. METHODS:
      Blood samples were collected from 39 healthy donors and 101 SLE patients
      fulfilling ACR criteria. Samples were collected from a total of 180 visits (58
      patients had 2 or more visits) of which 52 visits included a diagnosis of anemia.
      Healthy donors had only single visit. Total RNA, isolated from leukocytes, was
      analyzed by Taqman qPCR. Relative expression levels of I-IFN signature genes,
      chemokines, and miR-146a were determined by the DeltaDeltaCT method. Results were
      correlated with clinical data and analyzed by the Wilcoxon/Kruskal-Wallis test
      and Fisher's exact test. RESULTS: Significant increases in IFN score (p <
      0.0001), STAT1 (p < 0.0001), miR-146a (p < 0.0005), CCL2 (p = 0.0047), and CXCL10
      (p = 0.017), as well as a significant decrease in pri-miR-146a (p = 0.0002), were
      detected in the anemic SLE patient visits (n = 52) compared to non-anemic SLE
      visits (n = 128). Regardless of disease activity, lupus nephritis, or race,
      anemic SLE patients displayed significantly elevated levels of STAT1 and miR-146a
      compared to non-anemic SLE patients. CONCLUSIONS: STAT1 and miR-146a may be
      upregulated during inflammation and via proinflammatory cytokines and chemokines
      in SLE. Prolonged upregulation of STAT1 and miR-146a appears to play an important
      role in anemia in SLE patients.

PMID- 24292726
TI  - Today I wear a blue hat, too.

PMID- 24292729
TI  - Today I wear a blue hat.

PMID- 24292730
TI  - Antipsychotic formulation and one-year rehospitalization of schizophrenia
      patients: a population-based cohort study.
AB  - OBJECTIVE The authors compared the efficacy of long-acting injectable
      antipsychotics and oral antipsychotics on rehospitalization rate of community
      dwelling patients with schizophrenia who had frequent admissions. METHODS The
      cohort study of 14,610 patients was conducted by analyzing the Taiwan National
      Health Research Institutes data. The patients were divided into groups that
      received oral antipsychotics (risperidone, a different second-generation
      antipsychotic, or a first-generation antipsychotic) or long-acting injectable
      antipsychotics (risperidone, haloperidol, or flupenthixol). RESULTS One-year
      rehospitalization rates of the final cohort of 10,552 patients were the same for
      both groups (by long-acting injection, 27.3%; by oral administration, 27.3%).
      Secondary analysis of groups receiving long-acting injectable medication showed
      that haloperidol resulted in lower rehospitalization rates (haloperidol, 22.5%;
      risperidone, 27.1%; and flupenthixol, 29.5%). Patients' characteristics,
      including age, region, and insurance payments were significantly correlated with
      the risk of relapse (p<.05). CONCLUSIONS Except for injectable haloperidol, long
      acting injectable antipsychotics seem not to be superior to oral antipsychotics
      in reducing rehospitalization. 

PMID- 24292732
TI  - Case managers' perceptions of consumer work readiness and association with
      pursuit of employment.
AB  - OBJECTIVE The purpose of this study was to determine whether case managers'
      perceptions of consumers' work readiness-in the areas of the individual
      consumer's hygiene, social skills, medication adherence, psychiatric symptoms,
      and substance use-influence pursuit of employment. METHODS A cross-sectional
      survey study design was used to assess the role of staff perceptions in
      consumers' pursuit of employment. A hierarchical generalized linear model with a
      logit link function was used to analyze data from 1,556 consumers nested within
      data for 113 case manager caseloads. RESULTS Case managers' perception of work
      readiness was significantly associated with pursuit of employment. CONCLUSIONS
      The clients of case managers with less stringent criteria for pursuing employment
      were more likely to take positive steps toward employment. 

PMID- 24292731
TI  - Facilitators and barriers associated with implementation of evidence-based
      psychotherapy in community settings.
AB  - OBJECTIVE Despite widespread use of individual outpatient psychotherapies among
      community mental health centers (CMHCs), few studies have examined implementation
      of these psychotherapies. This exploratory qualitative study identified key
      themes associated with the implementation of an empirically supported
      psychotherapy in CMHCs. METHODS The authors conducted semistructured interviews
      with 12 key informants from four CMHCs that had implemented interpersonal and
      social rhythm therapy (IPSRT). Their responses were categorized into key themes.
      RESULTS Five major themes were identified: pretraining familiarity with IPSRT,
      administrative support for implementation, IPSRT fit with usual practice and
      clinic culture, implementation team and plan, and supervision and consultation.
      Discussion of these themes varied among participants from clinics considered
      successful or unsuccessful implementers. CONCLUSIONS Participants identified both
      key themes and several strategies for facilitating implementation. The findings
      suggest that when these key factors are present, outcome-enhancing treatments can
      be implemented and sustained, even in clinics with limited resources. 

PMID- 24292733
TI  - Parents' stigmatizing attitudes toward psychiatric labels for ADHD and
      depression.
AB  - OBJECTIVE There is concern that diagnostic labels for psychiatric disorders may
      invoke damaging stigma, especially for children. This study compared parents'
      stigma toward children with the symptoms of attention-deficit hyperactivity
      disorder (ADHD) or depression versus the same symptoms plus a psychiatric label.
      METHODS Parents (N=225) rated their stereotypes, prejudice, and social distance
      toward vignettes of children with a developmentally typical range of behaviors,
      symptoms that met DSM-IV-TR criteria for ADHD or depression, and the same
      symptoms plus a label of ADHD or depression. RESULTS Children described as having
      symptoms only were more stigmatized than children with typical behaviors (d=.97
      2.69). Adding a diagnostic label resulted in significant but small increases in
      stigma (d=.12-.23). CONCLUSIONS Parents highly stigmatized children with
      psychiatric problems, but adding a diagnostic label made only a small
      contribution to worsening the stigma. The benefits of seeking psychiatric
      services-accessing treatment and providing validation-may outweigh fears of
      labeling. 

PMID- 24292734
TI  - Social networks and arrest among persons with severe mental illness: an
      exploratory analysis.
AB  - OBJECTIVE This exploratory study examined whether social network structures among
      persons with severe mental illness-the size of the current friendship network and
      the frequency of contact with it-are related to lifetime arrest. METHODS Data
      from 119 individuals who participated in psychosocial rehabilitation programs in
      Los Angeles County were used. Hierarchical logistic regression modeling was
      applied. RESULTS Having frequent contact with the network was associated with a
      five times greater likelihood of lifetime arrest (odds ratio [OR]=4.99, 95%
      confidence interval [CI]=1.31-19.12), and having a larger network was associated
      with a 76% decrease in likelihood (OR=.24, CI=.06-.92). CONCLUSIONS Social
      network theories suggest that network structures influence attitudes and
      behaviors and access to resources among network members. Results indicate that
      friendship network structures in this population, typified by concentrated
      disadvantage, may be related to arrest and should be considered in future studies
      examining risk and protective factors for criminal justice involvement. 

PMID- 24292735
TI  - "Prosumers" and recovery.

PMID- 24292736
TI  - Alternative settings: unintended consequences.

PMID- 24292737
TI  - Alternative settings: unintended consequences: in reply.

PMID- 24292738
TI  - ICD-11 and DSM-5 classifications: a survey of Japanese psychiatrists.

PMID- 24292739
TI  - Disengagement in a torture treatment program.

PMID- 24292740
TI  - SAMHSA releases Behavioral Health, United States, 2012.

PMID- 24292743
TI  - Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein
      hydrolysate against high blood pressure in spontaneously hypertensive rats.
AB  - PURPOSE: This work determined the ability of hemp seed meal protein hydrolysate
      (HMH)-containing diets to attenuate elevated blood pressure (hypertension)
      development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma
      levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also
      determined. METHODS: Defatted hemp seed protein meal was hydrolyzed using
      simulated gastrointestinal tract digestion with pepsin followed by pancreatin,
      and the resulting HMH used as a source of antihypertensive peptides. The HMH was
      substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8
      weeks (preventive phase) or adult rats for 4 weeks (treatment phase). RESULTS:
      Feeding of young growing SHRs with HMH resulted in attenuation of the normal
      increases in systolic blood pressure (SBP) with an average value of ~120 mmHg
      when compared to the casein-only group of rats (control) with a maximum of 158 mm
      Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week
      period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison
      with 150 mmHg for the control rats. Plasma ACE activity was significantly (p <
      0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats
      (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054
      MUg/mL) when compared to control rats that were fed only with casein (0.151
      MUg/mL). CONCLUSIONS: The results suggest that HMH with strong hypotensive
      effects in SHRs could be used as a therapeutic agent for both the prevention and
      treatment of hypertension.

PMID- 24292744
TI  - Dietary patterns and risk of urinary tract tumors: a multilevel analysis of
      individuals in rural and urban contexts.
AB  - INTRODUCTION: Bladder cancer is the fourth most frequently diagnosed malignancy
      in males in Cordoba, Argentina. The evidence regarding an association between
      urinary tract tumors and dietary factors still remains controversial. Argentina
      has particular dietary habits, which have already been associated with cancer
      occurrence. PURPOSES: (a) To estimate the association of typical dietary patterns
      in Argentina on the occurrence of urinary tract tumors and (b) to assess the
      urban-rural context of residence and cancer occurrence dependency. METHODS: A
      case-control study of urinary tract tumors (n = 123, 41/82 cases/controls) was
      performed in Cordoba Province (Argentina), 2006-2011. A two-level logistic
      regression model was fitted, taking into account rural-urban residence. An
      exhaustive probabilistic sensitivity analysis (bias analysis) was performed.
      RESULTS: Southern Cone pattern, characterized by red meat, starchy vegetables and
      wine consumptions (OR 1.75 high versus low level of adherence to the pattern),
      and a medium adherence to a high-sugar drinks pattern, with high loadings for
      soft drinks (OR 2.55), were associated with increasing risk of urinary tract
      tumors. High adherence to the latter pattern was inversely associated (OR 0.72).
      The occurrence of urinary tract tumors was also linked to place of residence
      (urban-rural), explaining more than 20% of outcome variability and improving the
      above risk estimations. CONCLUSIONS: A high intake of red meat, starchy
      vegetables and wine, and a moderate intake of high-sugar drinks seem to be
      associated with increased risk of urinary tract tumors, with differences related
      to the context of residence.

PMID- 24292745
TI  - Long-term effect of altered nutrition induced by litter size manipulation and
      cross-fostering in suckling male rats on development of obesity risk and health
      complications.
AB  - OBJECTIVE: We investigated the long-term effect of pre-weaning nutrition on
      positive and/or adverse regulation of obesity risk and health complications in
      male Sprague-Dawley rats. DESIGN AND SUBJECT: Two experimental models were used
      in the present work: (1) To induce postnatal over- or normal nutrition, the
      litter size was adjusted to 4 (small litters-SL) and to 10 pups (normal litters
      NL) in the nest, (2) in suckling pups at day 10, we used cross-fostering to
      identify the effect of altered dietary environment on their future body fat
      regulation, food intake, blood pressure, and the duodenal and jejunal alkaline
      phosphatase activity. After weaning, these control (NL, SL) and cross-fostered
      (NL-SL, SL-NL) groups were exposed to standard laboratory diet. RESULTS: On day
      50, the SL in comparison with NL rats became heavier and displayed enhanced
      adiposity accompanied by significantly increased systolic blood pressure (19%)
      and duodenal (16%) and jejunal (21%) alkaline phosphatase (AP) activity. The
      impact of pre-weaning over-nutrition of NL-SL pups was associated with long
      lasting positive effect on obesity. In contrast, SL-NL rats submitted until
      weaning to the opposite normalized feeding condition on day 50 showed
      significantly decreased fat deposition (21%), systolic blood pressure (20%), and
      AP activity in duodenum and jejunum (14%). CONCLUSIONS: These results contribute
      to a better understanding of how early-acquired dietary habits determine the
      attenuation or prevention of obesity development in later life and can provide
      some benefit for optimizing the future dietary strategies in young and adult
      obese individuals.

PMID- 24292746
TI  - Vitamin B12 as a potential compliance marker for fish intake.
AB  - OBJECTIVES: The aim of the present study was to investigate whether the following
      four markers: vitamin B12, selenium, vitamin D, and parvalbumin may be used as
      compliance markers for fish intake. METHODS: Blood samples from a randomized
      cross-over herring intervention study (n = 32) were analysed by HPLC and
      immunochemistry. The criteria were that plasma or serum concentrations of
      candidate compliance markers after the herring diet should increase significantly
      compared to starting concentrations. In addition, the reference meat diet should
      not yield an increase in plasma concentration of the candidate marker. RESULTS:
      Vitamin B12 and selenium met the set criteria for indicating a correlation
      between the marker and fish intake with significant increases in serum
      concentrations at 8.9% (p = 0.008) and 4.6% (p = 0.02), respectively, after a 6
      week herring intervention (5 meals a week). Parvalbumin and 25-hydroxy vitamin D3
      levels did not increase significantly after the herring interventions.
      CONCLUSIONS: Vitamin B12 may be suitable as a compliance marker for fish intake.
      Although selenium also met the criteria, the change in selenium serum
      concentrations was small compared to the change in vitamin B12 levels.

PMID- 24292747
TI  - Alcohol flushing and positive ethanol patch test in patients with coronary
      spastic angina: possible role of aldehyde dehydrogenase 2 polymorphisms.
AB  - OBJECTIVE: Coronary spasm plays an important role in the pathogenesis of coronary
      heart disease (CHD) and angina pectoris caused by coronary spasm or coronary
      spastic angina (CSA) is prevalent in Japan. However, the precise mechanisms
      underlying coronary spasm are unclear. Alcohol intolerance is prevalent among
      East Asians, and we previously reported that coronary spasm could be induced by
      alcohol intake in CSA patients. We herein examined whether CSA is associated with
      alcohol intolerance in Japanese subjects. METHODS: The study subjects consisted
      of 80 CSA patients (57 men/ 23 women, mean age 62 +/- 12) and 52 non-CSA patients
      (25 men/27 women, mean age 63 +/- 10). The ethanol patch test (EPT) and
      questionnaire which evaluates flushing after ethanol intake, along with an
      examination of clinical features and laboratory chemistry data for CHD risk
      factors were done. Gender (male) and smoking were higher (p=0.007, and p=0.019,
      respectively) and plasma HDL cholesterol level was lower (p=0.035) in the CSA
      patients than in the non-CSA patients. Multivariable logistic regression analysis
      including age, EPT, smoking, and plasma HDL cholesterol level as independent
      variables revealed that positive EPT and smoking were significant predictors of
      CSA (p=0.011 and p=0.016, respectively). CONCLUSION: Positive EPT and alcohol
      flushing following alcohol intake, as well as smoking and plasma levels of HDL
      cholesterol, were significantly associated with CSA in Japanese patients.
      Therefore, alcohol ingestion as well as smoking is a significant risk factor for
      CSA in Japanese.

PMID- 24292749
TI  - Regression of follicular lymphoma of the duodenum following eradication of H.
      pylori infection.
AB  - A 64-year-old woman was referred for an examination of the upper gastrointestinal
      (GI) tract. Endoscopy showed an elevated lesion in the duodenum with central
      depression and multiple white granules. Biopsy specimens revealed lymphoid
      follicles composed predominantly of centrocytes with scattered centroblasts. The
      tumor cells were positive for bcl-2. The patient was diagnosed with follicular
      lymphoma and underwent antibiotic therapy for Helicobacter pylori (H. pylori)
      infection. The regression of the lesion was obvious. After 5.5 years of follow
      up, there has been no evidence of recurrence. This case suggests that H. pylori
      eradication therapy is effective for treating follicular lymphoma in the
      duodenum. 

PMID- 24292748
TI  - Increased expression of HBZ and Foxp3 mRNA in bronchoalveolar lavage cells taken
      from human T-lymphotropic virus type 1-associated lung disorder patients.
AB  - OBJECTIVE: Human T-lymphotropic virus type 1 (HTLV-I) causes adult T-cell
      leukemia/lymphoma (ATLL), and is associated with chronic inflammatory diseases,
      including inflammatory pulmonary diseases. HTLV-I bZIP factor (HBZ), which is
      expressed in all adult T-cell leukemia cells, plays a critical role in the
      development of lymphoma and systemic inflammation. HTLV-I is harbored by CD4(+) T
      cells that express forkhead box P3 (Foxp3), and HBZ interacts with Foxp3. This
      study investigated the chest computed tomography (CT) findings and expression of
      HBZ and Foxp3 in the bronchoalveolar lavage (BAL) cells from patients with HTLV-I
      associated lung disorders. METHODS: CT scans obtained from 37 patients (10 men
      and 27 women, aged 37-77 years) with HTLV-I-associated lung disorders were
      retrospectively evaluated. The expression levels of HBZ and Foxp3 mRNA in BAL
      cells and the levels of inflammatory cytokines in the BAL fluid (BALF) from
      patients were compared with those in control subjects. RESULTS: CT scans
      frequently revealed a diffuse panbronchiolitis (DPB)-like pattern, along with a
      nonspecific interstitial pneumonia (NSIP) pattern. An analysis of the BALF
      revealed lymphocytosis and increased expression of HBZ mRNA in patients with HTLV
      I-associated lung disorders. The expression of Foxp3 mRNA positively correlated
      with the percentages of lymphocytes present in the BALF. The inflammatory
      cytokine and IL-10 levels were significantly increased in the BALF from patients
      with HTLV-I-associated lung disorders. CONCLUSION: The NSIP pattern may be a
      manifestation of pulmonary involvement in HTLV-I-infected patients, as is the DPB
      like pattern. HBZ and Foxp3 likely have a role in the development of lung
      inflammation.

PMID- 24292750
TI  - Lacrimal gland marginal zone lymphoma: regression after treatment of chronic
      hepatitis C virus infection: case report and review of the literature.
AB  - A 43-year-old woman was first admitted to the ophthalmology clinic with the
      complaint of a mass compressing the right eye. Based on clinical and laboratory
      examinations she was diagnosed as having marginal zone lymphoma (MZL) of the
      right lacrimal gland in addition to hepatitis C virus (HCV) infection. After the
      treatment for HCV infection with pegylated interferon plus ribavirin, a
      radiographic response of the MZL was obtained; she remains in remission through
      thirty months of clinical follow-up. In this case, the treatment of HCV infection
      led to regression of MZL suggesting the necessity of testing for HCV infection
      and treatment of the HCV infection should be highly considered in all HCV
      positive patients with MZL's. 

PMID- 24292751
TI  - Successful non-surgical treatment of ruptured pyogenic liver abscess.
AB  - A 72-year-old man with a fever and abdominal pain was referred to our hospital.
      On admission, the patient exhibited the clinical signs of septic shock. Computed
      tomography revealed a rim-and septal-enhanced lesion in the left lobe of the
      liver with hemorrhage along the hepatic capsule. Because Klebsiella pneumoniae
      was detected in both the blood and aspirated abdominal fluid, the patient was
      diagnosed with a ruptured pyogenic liver abscess. He was successfully treated
      with percutaneous abscess drainage and the systemic administration of
      antibiotics. Non-surgical treatment for a ruptured pyogenic liver abscess is
      therefore effective in at least some cases. 

PMID- 24292752
TI  - Successful percutaneous coil embolization of a large and tortuous coronary artery
      to pulmonary artery fistula.
AB  - We herein report the case of a 73-year-old woman with a large and tortuous
      coronary artery to pulmonary artery fistula treated with percutaneous coil
      embolization. The patient was hospitalized due to unstable angina with an
      elevated serum troponin-T level. Coronary angiography revealed no significant
      atherosclerotic stenosis, with a large and tortuous coronary artery to pulmonary
      artery fistula originating from the proximal portion of the left anterior
      descending artery. We successfully performed percutaneous coil embolization of
      the fistula. In this case, 320-slice multidetector computed tomography played a
      pivotal role in the diagnosis and percutaneous intervention. 

PMID- 24292753
TI  - Successful treatment of chronic intractable itching using oral pregabalin in a
      patient with diabetes and systemic prurigo nodularis: a case report of an
      iliopsoas muscle abscess.
AB  - A 73-year-old Japanese man developed chronic intractable itching due to prurigo
      nodularis. High-dose glucocorticoid ointment failed, and the treatment resulted
      in poor glycemic control. Repeated scratching caused hematogenous bacterial
      dissemination via cutaneous injuries, resulting in the formation of iliopsoas and
      spinal epidural abscesses that required long-term antibiotic treatment.
      Pregabalin was administered to treat the pruritus, and a considerable improvement
      was observed. A reduction in the dose and intensity of the topical
      corticosteroids improved the patient's glycemic control, resulting in the
      complete resolution of the abscesses. Pregabalin significantly improved the
      patient's pruritus and decreased the risk of infection. 

PMID- 24292754
TI  - Slowly progressive type 1 diabetes treated with metformin for five years after
      onset.
AB  - A 52-year-old man was diagnosed with slowly progressive type 1 diabetes (SPIDDM).
      We expected him to quickly progress to an insulin-dependent state due to a high
      anti-glutamic acid decarboxylase antibody titer (23.9 U/mL). At SPIDDM diagnosis,
      he was in a non-insulin-dependent state, with a fasting serum C-peptide
      immunoreactivity level of 2.5 ng/mL. Therefore, we prescribed metformin. His
      glycemic control remained stable, and his intrinsic insulin secretion capacity
      was maintained for five years. Although one case is insufficient to draw firm
      conclusions, this report suggests that metformin is a therapeutic choice for
      SPIDDM when the insulin secretion capacity is maintained. 

PMID- 24292755
TI  - Sarcoidosis in a chronic dialysis patient diagnosed by sarcoidosis-related
      hypercalcemia with no common systemic clinical manifestations: a case report and
      review of the literature.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown origin. We herein
      report a case of sarcoidosis in a chronic dialysis patient diagnosed by
      hypercalcemia without any common clinical manifestations. The onset of
      sarcoidosis in chronic dialysis patients is rare; to the best of our knowledge,
      only 23 cases have been reported. Evaluation of the 23 previously published cases
      revealed that a diagnosis of sarcoidosis was often achieved by the presence of
      sarcoidosis-related hypercalcemia without any common clinical presentations, as
      in the present case. This characteristic may arise from a specific immune
      deficiency and the unique physiology of 1,25-dihydroxyvitamin D3, a main cause of
      sarcoidosis-related hypercalcemia, in chronic dialysis patients. These clinical
      features may be useful to understand the pathogenesis of sarcoidosis. 

PMID- 24292756
TI  - Anaplastic large cell lymphoma mimicking fibrosing mediastinitis.
AB  - Fibrosing mediastinitis is rare. One type of this disease is idiopathic fibrosing
      mediastinitis. It is necessary to rule out malignancy in order to accurately
      diagnose fibrosing mediastinitis. We herein report a case of anaplastic large
      cell lymphoma diagnosed three months after a preliminary diagnosis of fibrosing
      mediastinitis. Glucocorticoid therapy was not successful in controlling disease
      progression. Immediately after initiating chemotherapy for lymphoma, the
      patient's symptoms improved dramatically and the mediastinal lesion decreased in
      size. Although few similar cases have been reported, hidden malignancy may
      present as fibrosing mediastinitis. Therefore, physicians should consider the
      probability of malignancy in patients with fibrosing mediastinitis because
      treatments may vary accordingly. 

PMID- 24292757
TI  - Mycobacterium shinjukuense lung disease that was successfully treated with
      antituberculous drugs.
AB  - An 80-year-old woman was referred to our hospital due to a persistent productive
      cough. Acid-fast staining and a commercial Mycobacterium tuberculosis
      identification kit with TRC (TRC kit) were positive. However, a false-positive
      result on the TRC kit was suspected because Mycobacterium tuberculosis was not
      detected in the sputum culture. Finally, Mycobacterium shinjukuense was detected
      in an analysis of the rpoB and hsp65 gene sequences. As the diagnostic criteria
      proposed by the American Thoracic Society were met, a diagnosis of Mycobacterium
      shinjukuense lung disease was made. Following treatment with isoniazid,
      rifampicin and ethambutol with drug susceptibility, the patient's acid-fast
      culture became negative, and the areas of opacity improved. 

PMID- 24292758
TI  - Propylthiouracil-induced bronchiolitis obliterans organizing pneumonia.
AB  - Propylthiouracil (PTU) is commonly used to treat hyperthyroidism. However, it is
      also associated with a number of adverse events. In particular, pulmonary
      complications, although rare, can be serious. Therefore, early detection is
      paramount. We herein describe a first case of PTU-induced bronchiolitis
      obliterans organizing pneumonia (BOOP) pathologically confirmed on a surgical
      lung biopsy. The present case shows that early detection coupled with the
      immediate withdrawal of PTU can lead to a successful resolution of symptoms and
      radiographic abnormalities without the need for corticosteroids. Although rare,
      PTU-induced BOOP should be considered in the differential diagnosis of pulmonary
      opacity in patients receiving PTU therapy. 

PMID- 24292759
TI  - Acquired von Willebrand syndrome associated with Hashimoto's thyroiditis and
      subcutaneous mucosa-associated lymphoid tissue lymphoma.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with
      laboratory findings similar to those of congenital von Willebrand disease. We
      herein report a case of AVWS associated with Hashimoto's thyroiditis and
      subcutaneous mucosa-associated lymphoid tissue lymphoma. An IgG autoantibody
      against von Willebrand factor (VWF) was detected. The antibody bound to VWF but
      did not inhibit VWF activity. Rapid clearance of VWF seemed to be the cause of
      AVWS in the present case. VWF-containing concentrates stopped the bleeding. Even
      if such a complication is rare, for AVWS patients, prompt recognition of the
      underlying mechanism can save lives. 

PMID- 24292760
TI  - Neuromyelitis optica preceded by hyperCKemia and a possible association with
      coxsackie virus group A10 infection.
AB  - We report the case of a 48-year-old woman presenting with an elevated serum
      creatine kinase level (hyperCKemia) associated with an initial attack of
      neuromyelitis optica (NMO). The patient initially showed general fatigue with
      fever. Laboratory findings showed hyperCKemia and subsequently she developed a
      slight weakness of both lower limbs and reduced vision. Autoantibodies against
      aquaporin 4 were found in her serum, and a retrospective examination of viral
      titers indicated a possible coxsackie virus group A10 infection. The present case
      suggests that hyperCKemia-mediated disease onset is involved in some patients
      with NMO, and furthermore, it may be related to muscular destruction associated
      with viral infection. 

PMID- 24292761
TI  - Disseminated gonococcal infection in an elderly Japanese man.
AB  - We herein present the case of a 69-year-old Japanese man who had unprotected
      sexual contact with a local commercial sex worker in an East Asian country and
      was diagnosed as having disseminated gonococcal infection (DGI). The organism was
      confirmed to be Neisseria gonorrhoeae based on 16S rRNA sequencing and positive
      results for the cppB gene. This case indicates that a diagnosis of DGI should
      also be considered in elderly individuals. DGI potentially causes many
      complications, and the pathogen has recently been reported to be resistant to
      various antibiotics. Physicians must therefore pay more attention to the possible
      occurrence of DGI in various clinical settings. 

PMID- 24292762
TI  - Group A streptococcal meningitis in a patient with palmoplantar pustulosis.
AB  - A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent
      history of cranial surgery and a persistent upper airway infection presented with
      a high fever and deep coma. The patient was diagnosed with Group A Streptococcal
      meningitis and promptly treated with antibiotics. Although his general condition
      recovered well, sensorineural hearing loss and facial palsy remained. Group A
      Streptococcal meningitis is a rare condition, and its typical clinical picture
      and epidemiological features remain poorly understood. Physicians need to be more
      aware of this infection, which is extremely rare but frequently causes various
      complications and yields a high mortality. 

PMID- 24292763
TI  - Duplication of the etrahepatic bile duct with a benign stricture.

PMID- 24292764
TI  - (18)F-FDG-PET CT findings in a patient with early-phase cardiac sarcoidosis.

PMID- 24292765
TI  - Granulomatous-lymphocytic interstitial lung disease in a patient with common
      variable immunodeficiency.

PMID- 24292766
TI  - Cholesterol crystals in pleural effusion.

PMID- 24292767
TI  - Susceptibility-weighted imaging effectively reveals small cavernomas.

PMID- 24292768
TI  - Multiple tumoral calcinosis in systemic sclerosis.

PMID- 24292769
TI  - Magnetic resonance myelography in a patient with cerebrospinal fluid hypovolemia.

PMID- 24292770
TI  - Diversity of lactic acid bacteria associated with fresh coffee cherries in
      Taiwan.
AB  - A total of 102 lactic acid bacteria (LAB) were isolated from three different
      coffee farms in Taiwan. These isolates were classified and identified by the
      restriction fragment length polymorphism analysis and sequencing of 16S ribosomal
      DNA. Heterofermentative Leuconostoc, and Weissella species were the most common
      LAB found in two farms located at an approximate altitude of 800 m. Lactococcus
      lactis subsp. lactis was the most common LAB found in the remaining farm was
      located at an approximate altitude of 1,200 m. It is therefore suggested that the
      altitude and climate may affect the distribution of LAB. On the basis of
      phylogenetic analysis, two strains included in the genera Enterococcus were
      considered as two potential novel species or subspecies. In addition, a total of
      34 isolates showed the antifungal activity against Aspergillus flavus. Moreover,
      seven Lactococcus lactis subsp. lactis strains and one Enterococcus faecalis
      strain were found to have bacteriocin-like inhibitory substance-producing
      capability. These results suggest that various LAB are associated with fresh
      coffee cherries in Taiwan. Some of the isolates found in this study showed
      potential as antifungal agents. 

PMID- 24292771
TI  - Acute toxicity of copper, zinc, and ammonia to larvae (Glochidia) of a native
      freshwater mussel Echyridella menziesii in New Zealand.
AB  - Adult New Zealand freshwater mussel Echyridella menziesii were collected from
      three locations in the North Island of New Zealand. In a series of tests that
      followed standard test guidance, glochidia were exposed to either dissolved
      copper (Cu), zinc (Zn), or total ammonia nitrogen (TAN) for 6, 24, or 48 h (20 
      degrees C, pH 7.8, water hardness 30 mg L(-1) as CaCO3, dissolved organic carbon
      [DOC] 2.0-2.9 mg L(-1)). Of the three contaminants and tests that met control
      survival criteria, mussel larvae (glochidia) were most sensitive to Cu exposure
      (48-h EC50 = 1.7-3.4 MUg L(-1), 48-h no observed effect concentrations (NOEC) of
      1.3-2.6 MUg L(-1)). The Zn 48-h EC50 concentrations were 229-337 MUg L(-1) and
      the 48-h NOEC values were 128-240 MUg L(-1). Compared with other native New
      Zealand species, glochidia were also relatively sensitive to TAN exposure (48-h
      EC50 12-15 mg TAN L(-1) [pH 7.8], 48-h NOEC 8-10 mg TAN L(-1)). Comparison of our
      data with those of previous studies on North American freshwater mussels
      indicates that (1) E. menziesii are among those aquatic species most sensitive to
      acute Cu or TAN exposure; and (2) E. menziesii juveniles would not be adequately
      protected by current ANZECC water quality guidelines for TAN or Cu. Inclusion of
      North American juvenile mussel data in a revision of the current ANZECC water
      quality guideline (95th percentile) for chronic ammonia exposure results in a
      decrease from 0.9 mg to 0.2 mg TAN L(-1) (pH 8).

PMID- 24292772
TI  - Mechanism underlying ATP release in human epidermal keratinocytes.

PMID- 24292774
TI  - Vestibular schwannoma surgery via the retrosigmoid transmeatal approach.
AB  - BACKGROUND: Aims of modern vestibular schwannoma surgery are complete tumor
      resection with functional facial nerve and hearing preservation, if possible.
      Here we present our technique of bimanual dissection for vestibular schwannoma
      resection through the retrosigmoid approach. METHOD: A slightly curved surgical
      incision is planned two fingers behind the ear extending from the level of the
      tip of the ear to 1 cm below the mastoid tip. The retrosigmoid craniectomy
      exposes the sinus knee, the inferior border of the transverse sinus, the medial
      border of the sigmoid sinus and horizontal segment of the occipital squama. The
      dura is opened under the microscope in semilunar fashion parallel to the course
      of the sigmoid sinus. We open the IAC with a high-speed diamond drill from
      lateral to medial, opening the canal for 180 degrees  of its circumference. The
      intrameatal part of the vestibular schwannoma is partially removed and the facial
      nerve identified Thereafter, we open the capsule and debulk the tumor with an
      ultrasonic surgical aspirator in the CPA. Once the tumor's mass is significantly
      reduced, a bimanual dissection of the cleavage plane between capsule and the
      surrounding arachnoid is performed. Starting from below, the capsule is elevated
      with a tumor grasping forceps and the arachnoid membrane is peeled off. Following
      the cleavage plane, the facial nerve is separated in a medial to lateral
      direction from the VS's capsule. Throughout the whole procedure the field is
      irrigated with warm Ringer's solution. We seal the drilled posterior lip of the
      IAC as well as eventually opened mastoid air cells with a free muscle or fat
      patch. CONCLUSION: Vestibular schwannoma surgery through the retrosigmoid
      approach is a safe procedure that allows gaining good functional results.

PMID- 24292773
TI  - Intercellular skin barrier lipid composition and organization in Netherton
      syndrome patients.
AB  - Netherton syndrome (NTS) is a rare genetic skin disease caused by mutations in
      the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho
      epithelial Kazal-type-related inhibitor. NTS patients have profoundly impaired
      skin barrier function. As stratum corneum (SC) lipids have a crucial role in the
      skin barrier function, we investigated the SC lipid composition and organization
      in NTS patients. We studied the SC lipid composition by means of mass
      spectrometry, and the lipid organization was examined by infrared spectroscopy
      and X-ray diffraction. Decreased free fatty acid (FFA) chain length and increased
      levels of monounsaturated FFAs were observed in the SC of NTS patients compared
      with controls. Furthermore, the level of short-chain ceramides (CERs) was
      enhanced in NTS patients and a strong reduction in long-chain CER levels was seen
      in several patients. The changes in lipid composition modified the lipid
      organization leading to an increased disordering of the lipids compared with the
      controls. In addition, in a subgroup of patients the organization of the lipid
      layers changed dramatically. The altered FFA and CER profiles in NTS patients
      corresponded to changes in the expression of enzymes involved in SC lipid
      processing. The observed changes in lipid composition, lipid organization, and
      enzyme expression are likely to contribute to the barrier dysfunction in NTS. 

PMID- 24292775
TI  - Overcoming CSF overdrainage with the adjustable gravitational valve proSA.
AB  - BACKGROUND: Despite progress in shunt valve technology, CSF overdrainage is still
      one of the most frequent complications in shunt-treated hydrocephalus.
      Particularly with regard to young and adolescent patients, treatment of manifest
      overdrainage is complicated by several hardly influenceable factors such as
      increasing height and mobility. Therefore, the aim of this study was to evaluate
      the therapeutic efficiency of the new adjustable gravitational valve, proSA.
      METHODS: Sixty-four shunt-treated young hydrocephalus patients aged 1.8-41.4
      years (15.5 +/- 10.5 years) suffering from clinical and/or radiological
      overdrainage underwent shunt revision surgery with the implantation of the new
      proSA valve. Clinical outcome after a 1-year follow-up period, pumping function
      of the valve chambers as well as the number of necessary postoperative valve
      adjustments were examined. RESULTS: Fifty-five patients completed the study as
      planned. All reported a significant improvement of their clinical condition; 91 %
      described a complete resolution in symptoms related to overdrainage.
      Preoperatively, more than 85 % of the valve chambers showed no or very slow
      refilling with CSF. After a year of proSA treatment, more than 90 % exhibited a
      normal valve chamber function. During the follow-up period, a total of 136 valve
      adjustments were necessary. None of the proSA valves had to be surgically
      revised. CONCLUSIONS: The postoperative adjustability of the opening pressure
      level is the advantage of the new gravitational valve. The good clinical outcome
      is attributed to the new valve technology. The proSA appears to be a promising
      shunt valve to overcome overdrainage in adolescent and adult hydrocephalus
      patients.

PMID- 24292776
TI  - Surgical management of diffuse low-grade gliomas associated with other
      intracranial diseases.
AB  - BACKGROUND: The association of diffuse, low-grade glioma (DLGG) with other
      intracranial pathologies is a rare condition, raising the question of what
      constitutes its most effective therapeutic management. It is not known whether
      this is a simple coincidence or whether there is a higher significant risk
      involved with the co-existence of DLGG and another disease. We report the first
      consecutive series of nine patients who underwent surgical resection for such a
      glioma. METHOD: We reviewed DLGGs removed between 1998 and 2013 that were
      associated with another intracranial pathology. For all cases, we collected and
      analyzed information regarding clinico-radiological features, surgical
      procedures, and clinical outcomes. RESULTS: Nine consecutive patients (four men,
      five women, mean age: 38.8 years) presented with a conjunction of DLGG and
      another disease: two cases of vestibular schwannoma, two pituitary adenomas, two
      meningiomas, one lymphoma, one arteriovenous malformation, and one case of
      multiple sclerosis. The DLGG was diagnosed because of seizures in four patients
      and incidentally in the other five patients. The average delay between the
      diagnosis of the glioma and its resection was 40.8 months (range 1-84 months).
      The mean follow-up after surgery was 43 months (6-120 months). Gross-total or
      subtotal resection was achieved in all cases. There were no cases of mortality or
      permanent morbidity associated with surgery. The Karnofsky Performance Scale
      score was 90 or 100 in all cases. The associated pathology was treated surgically
      in three cases, medically in four cases, and tracked under observation in two
      cases. These intracranial diseases, especially meningiomas and pituitary
      adenomas, might have a significant higher risk to be associated with DLGGs in
      comparison with their incidence and prevalence in the general population.
      CONCLUSIONS: Active management of this rare, dual pathology allows patients to
      enjoy a normal and prolonged quality of life. We therefore suggest considering
      early and maximal surgical resection as the first therapeutic option for DLGGs
      combined with another intracranial disease, as is done in the case of isolated
      DLGGs.

PMID- 24292777
TI  - Surgical management of cervical spondylotic myelopathy - indications for
      anterior, posterior or combined procedures for decompression and stabilisation.
AB  - BACKGROUND: The authors describe their experience with the choice of anterior,
      posterior and combined approaches for the surgical treatment of spondylotic
      myelopathy. METHODS: Description of surgical anatomy, surgical technique,
      indications, limitations, complications, specific perioperative considerations
      and specific information to give to the patient about surgery and potential risks
      and a summary of 10 key points is given. CONCLUSIONS: If the disease extends
      behind the posterior vertebral body and if reestablishing spinal sagittal and
      coronal balance is an aim, then the anterior approach is the best choice. In
      cases of predominant posterior spinal cord compression and lordotic configuration
      the posterior approach should be preferred. Decompression of three or more
      levels, especially in combination with poor bone quality, requires a combined
      approach.

PMID- 24292778
TI  - Unveiling the electronic origin of anion order in CrO(2-x)F(x).
AB  - Electron-diffraction and high-resolution lattice images reveal superstructure
      stripes with wave vectors of (1/3, 0, 1/3) and (-1/3, 0, 1/3), which are
      associated with the ordered arrangement of F(-). Charge density distribution
      suggests that these stripes manifest themselves electronically as F(-)-Cr(3+)-F(
      ) zigzag chains, driven by the anisotropic charge interaction of F(-) anions. 

PMID- 24292779
TI  - Investigation of targeted biomolecules in a micro-fluxgate-based bio-sensing
      system.
AB  - An investigation of targeted biomolecules was accomplished by combining a micro
      fluxgate-based bio-sensing system and Dynabeads. The fluxgate sensor for
      biomolecule detection was fabricated by Micro Electro-Mechanical system
      technology, including thick photoresist lithography, electroplating and chemical
      wet etching. The magnetic core of the sensor was made of Fe-based amorphous
      ribbon core and three dimension solenoid coils were used as magnetic sensitive
      elements. The micro-fluxgate-based bio-sensing system was characterized firstly
      in different concentrations of Dynabeads, and a concentration as low as 100 ng/ml
      was detected with an external dc magnetic field in the range of 525 MUT to 875
      MUT. Sandwich assays are performed using antibody-antigen pair combination of
      biotin-streptavidin on a separated Au film substrate surface with a self
      assembled layer. Detection of Alpha Fetoprotein antigens with different
      concentrations was performed and a minimum detectable concentration of 1 pg/ml
      was achieved by the bio-sensing system. It is of considerable interest due to its
      potential application in the biomedical field based on known specific binding of
      target and labels. 

PMID- 24292780
TI  - Mortality, oxidative stress and hepatotoxicity in juvenile African catfish,
      Clarias gariepinus Burchell, exposed to lead and cypermethrin.
AB  - In this study, juvenile catfish (Clarias gariepinus) were exposed to 2 mg/L Pb,
      0.5 MUg/L cypermethrin, or both for 96 h. Survival ranged from 100% in both
      treatments without cypermethrin, to 50% in fish exposed to cypermethrin only or
      the mixture. There were significant decreases in liver lysozyme, gamma-glutamyl
      transpeptidase, and alanine aminotransferase activities in fish exposed to
      cypermethrin or the mixture. Liver aspartate aminotransferase activity (AST)
      showed a significant reduction after exposure to Pb or cypermethrin alone, and
      the effect of the mixture on AST was additive or potentially synergistic. Liver
      lipid peroxidation (LPO) was increased in fish exposed to the mixture compared to
      those exposed to cypermethrin only, indicating that Pb presence enhanced LPO
      caused by cypermethrin. Our study demonstrates the potential for toxic
      interaction between Pb and cypermethrin in fish and suggests that due to the
      varying responses to contaminant mixtures in our study, researchers should
      consider using a variety of biomarkers.

PMID- 24292781
TI  - Droplet-based in situ compartmentalization of chemically separated components
      after isoelectric focusing in a Slipchip.
AB  - Isoelectric focusing (IEF) is a powerful and widely used technique for protein
      separation and purification. There are many embodiments of microscale IEF that
      use capillary or microfluidic chips for the analysis of small sample volumes.
      Nevertheless, collecting the separated sample volumes without causing remixing
      remains a challenge. Herein, we describe a microfluidic Slipchip device that is
      able to efficiently compartmentalize focused analyte bands in situ into
      microdroplets. The device contains a microfluidic "zig-zag" separation channel
      that is composed of a sequence of wells formed in the two halves of the Slipchip.
      The analytes are focused in the channel and then compartmentalised into droplets
      by slipping the chip. Importantly, sample droplets can be analysed on chip or
      collected for subsequent analysis using electrophoresis or mass spectrometry for
      example. To demonstrate this approach, we perform IEF separation using standard
      markers and protein samples, with on-chip post-processing. Compared to
      alternative approaches for sample collection, the method avoids remixing, is
      scalable and is easily hyphenated with the other analytical methods. 

PMID- 24292782
TI  - Discovery and exploitation of AZADO: the highly active catalyst for alcohol
      oxidation.
AB  - The oxidation of primary and secondary alcohols to the corresponding aldehydes
      (or carboxylic acids) or ketones is a fundamental transformation in organic
      synthesis. Stable organic nitroxyl radicals as represented by 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO) (1) have been used extensively to catalyze
      the oxidation of a number of alcohol substrates employing environmentally benign
      co-oxidants such as bleach (NaOCl) or PhI(OAc)2. Although TEMPO oxidation is
      better known as a method for selective oxidation of primary alcohols to the
      corresponding aldehydes, the TEMPO-based method is not very efficient for the
      oxidation of structurally hindered secondary alcohols. We designed and
      synthesized 2-azaadamantane N-oxyl [AZADO (11)] and 1-Me-AZADO (20), a
      structurally less hindered class of nitroxyl radical. AZADOs were found to
      exhibit excellent catalytic activity enabling oxidation of a variety of alcohols
      with which TEMPO exhibits poor reactivity. Based on structure-activity
      relationships (SAR) employing AZADO (11), 1-Me-AZADO (20), 1,3-dimethyl-AZADO
      (33), 9-azabicyclo[3.3.1]nonane-N-oxyl [ABNO (34)] and 9-azanoradamantane N-oxyl
      [Nor-AZADO (37)], we concluded that the alpha-methyl group flanked nearby the
      nitroxyl group affects the reactivity for the oxidation of sterically hindered
      alcohols and the azaadamantane skeleton contributes to the high turnover of the
      catalyst. The highly active nature of AZADOs spurred us to exploit their further
      use in alcohol oxidations. A facile, green, one-pot oxidation of primary alcohols
      to carboxylic acids with broad substrate applicability has been developed by
      employing an expedient catalytic system consisting of the oxoammonium salt [1-Me
      AZADO(+)X(-) (X=Cl, BF4)]/NaClO2. The synthetic use of AZADOs and the related
      nitroxyl radicals/oxoammonium salts-based methods for alcohol oxidation have been
      demonstrated in several total syntheses of natural products. We also describe the
      development of a Nor-AZADO (37)/DIAD/AcOH method that offers exceptionally mild
      and highly chemoselective oxidation of alcohols.

PMID- 24292783
TI  - Quantum chemical study for radical-induced DNA effects and damage.
AB  - Differences in molecular interaction between bases (adenine (A), guanine (G), and
      cytosine (C)) and the methyl (Me)-radical were investigated by perturbation
      analysis using the quantum chemical method. Part of the source of damage to the
      DNA was elucidated at the molecular level. In the reaction of each of the
      saccharide derivatives (dA, dG, and dC) with Me-radical, the reactivity of dG
      (~dA) is more than about 10 times larger than that of dC. Therefore, it is
      expected that the base G (and A) was more than about 10 times than the base C in
      radical-reactivity of the base. For the reaction of dA and dG with the radical,
      the C(8) site of the partial purine ring of dA and dG, and the C(5) site of the
      pyrimidine ring of dC were the main reaction sites for methylation. In the
      reaction of DNA composed of hydrogen-bonded base pairs G-C and A-T with the
      radical, the purine ring in the constituent base G reacted preferentially with
      the radical to yield 8-methyl-guanines. 

PMID- 24292784
TI  - Continuous wavelet transforms for the simultaneous quantitative analysis and
      dissolution testing of lamivudine-zidovudine tablets.
AB  - Dissolution testing has a very vital importance for a quality control test and
      prediction of the in vivo behavior of the oral dosage formulation. This requires
      the use of a powerful analytical method to get reliable, accurate and precise
      results for the dissolution experiments. In this context, new signal processing
      approaches, continuous wavelet transforms (CWTs) were improved for the
      simultaneous quantitative estimation and dissolution testing of lamivudine (LAM)
      and zidovudine (ZID) in a tablet dosage form. The CWT approaches are based on the
      application of the continuous wavelet functions to the absorption spectra-data
      vectors of LAM and ZID in the wavelet domain. After applying many wavelet
      functions, the families consisting of Mexican hat wavelet with the scaling factor
      a=256, Symlets wavelet with the scaling factor a=512 and the order of 5 and
      Daubechies wavelet at the scale factor a=450 and the order of 10 were found to be
      suitable for the quantitative determination of the mentioned drugs. These wavelet
      applications were named as mexh-CWT, sym5-CWT and db10-CWT methods. Calibration
      graphs for LAM and ZID in the working range of 2.0-50.0 ug/mL and 2.0-60.0 ug/mL
      were obtained measuring the mexh-CWT, sym5-CWT and db10-CWT amplitudes at the
      wavelength points corresponding to zero crossing points. The validity and
      applicability of the improved mexh-CWT, sym5-CWT and db10-CWT approaches was
      carried out by the analysis of the synthetic mixtures containing the analyzed
      drugs. Simultaneous determination of LAM and ZID in tablets was accomplished by
      the proposed CWT methods and their dissolution profiles were graphically
      explored.

PMID- 24292785
TI  - Impact of physicochemical profiling for rational approach on drug discovery.
AB  - Solid-state characterization plays a vital role in lead optimization and
      candidate selection with the appropriate physicochemical properties for proper
      oral dosage formulation. Aqueous solubility is an important parameter in the
      successful development of oral dosage formulation since poor aqueous solubility
      limits absorption. In this study, we summarized an efficient approach using a
      small amount of sample for solid-state characterization, including thermodynamic
      solubility, which is defined as physicochemical profiling. By using the
      physicochemical profiling results of 75 anti-cancer drugs and clinical
      candidates, we examined the relationship between thermodynamic solubility and
      molecular structural parameters and assessed the effects of thermodynamic
      solubility on pharmacokinetic profile for rational soluble drug design. The Log
      DpH 7.4, aromatic ring count, and hydrogen bond count were good indicators for
      predicting sparingly soluble compounds that increase the lattice energy because
      of pi-pi stacking and hydrogen bonds, resulting in lowered thermodynamic
      solubility. The level of thermodynamic solubility in simulated intestinal fluid
      (pH 6.8) in the presence and absence of bile acid, which is required for minimal
      acceptable bioavailability (>30%), was 1 ug/mL and 10 ug/mL, respectively.
      Physicochemical profiling, which includes thermodynamic solubility considering
      its solid-state properties, contributes to rational lead optimization and
      efficient candidate selection for drug development.

PMID- 24292786
TI  - Synthesis and structure-activity relationship of naphtho[1,2-b]furan-2
      carboxamide derivatives as melanin concentrating hormone receptor 1 antagonists.
AB  - The discovery that novel naphtho[1,2-b]furan-2-carboxamides containing linked
      piperidinylphenylacetamide groups serve as melanin concentrating hormone receptor
      1 (MCH-R1) antagonists is described. An extensive structure-activity relationship
      (SAR) study, probing members of this family that contain a variety of aryl and
      heteroaryl groups at C-5 of the naphtho[1,2-b]furan-2-carboxamide skeleton and
      having different chain linker lengths, led to the identification of the 5-(4
      pyridinyl) substituted analog 10b as a highly potent MCH-R1 antagonist with an
      IC50 value of 3 nM. This substance also displays good metabolic stability and it
      does not significantly inhibit cytochrome P450 (CYP450) enzymes. However, 10b has
      unacceptable oral bioavailability.

PMID- 24292787
TI  - Synthesis and structure-activity relationships of novel zwitterionic compounds as
      peroxisome proliferator activated receptor alpha/gamma dual agonists with
      improved physicochemical properties.
AB  - We describe herein the design, syntheses and structure-activity relationships
      (SAR) of novel zwitterionic compounds as non-thiazolidinedion (TZD) based
      peroxisome proliferator activated receptor (PPAR) alpha/gamma dual agonists. In
      the previous report, we obtained compound 1 showing potent PPARalpha/gamma dual
      agonistic activities, together with a great glucose lowering effect in the db/db
      mice. However, this compound possessed fatal issues such as potent cytochrome
      P450 (CYP)3A4 direct inhibitory activity. Thus, we carried out the medicinal
      optimization to improve these while maintaining the potent PPAR agonistic
      activity. As a result, the issues were addressed by changing the furan ring to a
      low lipophilic 1,3,4-oxadiazole ring. Additionally, these oxadiazole derivatives
      exhibited a significant decrease in plasma glucose and plasma triglyceride levels
      without marked weight gain. 

PMID- 24292788
TI  - Determination of selected nitropolycyclic aromatic hydrocarbons in water samples.
AB  - A new method for the analysis of selected nitropolycyclic aromatic hydrocarbons
      (NPAHs) at ultra-trace levels in water samples is proposed. Particulate NPAHs
      were collected on a GC glass fiber filter. Soluble NPAHs were collected on a C18
      Empore disk. After simple clean-up and concentration of NPAHs in both phases, the
      NPAHs were analyzed using HPLC equipped with clean-up, reducer, concentration and
      chemiluminescence detection units. The proposed method showed good linear
      calibration curves with correlation coefficients (r(2)) ranging from 0.9954 to
      0.9998. The limits of detection ranged from 0.013 to 0.15 nmol/L (soluble NPAHs)
      and from 0.01 to 0.13 nmol/L (particulate NPAHs) for 5 NPAHs [(9-nitroanthracene,
      1-nitropyrene, 6-nitrochrysene (6-NC), 7-nitrobenz[a]anthracene and 6
      nitrobenzo[a]pyrene] having 3 to 5 rings analyzed, when 1.5 L of water sample was
      used. The repeatability for soluble NPAHs ranged between 4.2 and 6.8% (n=5),
      while for particulate NPAHs, it varied between 2.2 and 2.8% (n=5). The proposed
      method successfully determined the above NPAHs expect 6-NC in river water
      samples, suggesting that this method is suitable for the ultra-trace analysis of
      NPAHs in water samples.

PMID- 24292789
TI  - Iontophoretic transdermal delivery of glycyrrhizin: effects of pH, drug
      concentration, co-ions, current intensity, and chemical enhancers.
AB  - The aim of the present study was to evaluate the feasibility of transdermal
      delivery of glycyrrhizin, an agent used in the treatment of chronic hepatitis C,
      by cathodal iontophoresis using Ag/AgCl electrodes in vitro. The effects of donor
      pH (pH 4-7), concentration of drug (0.025-0.2% (w/v)), concentration of external
      chloride ions (Cl(-)) (0-133 mM), current strength (0-0.5 mA/cm(2)), and
      permeation enhancers (urea and Tween 80) on the skin permeability of glycyrrhizin
      were examined in in vitro skin permeation studies using porcine ear skin as the
      membrane. The cumulative amount of permeated glycyrrhizin and the steady-state
      skin permeation flux of glycyrrhizin across porcine skin increased in a pH
      dependent manner. The skin permeability of glycyrrhizin was independent of the
      concentration of drug and competed only with a high external Cl(-) concentration.
      The skin permeation flux of glycyrrhizin increased with the current
      (R(2)=0.8955). The combination of iontophoresis and enhancers provided an
      additive or synergistic effect, and a skin permeation flux of about 60 ug/h/cm(2)
      was achieved. The plasma concentration of glycyrrhizin in humans, extrapolated
      from the in vitro steady-state permeation flux across porcine skin, was within
      the therapeutic level. These results suggest that cathodal iontophoresis can be
      used as a transdermal drug delivery system for glycyrrhizin using reasonable
      patch sizes and acceptable levels of current intensity.

PMID- 24292790
TI  - Synthesis and antioxidant activity of styrylsulfonylmethyl 1,3,4-oxadiazoles,
      pyrazolyl/isoxazolyl-1,3,4-oxadiazoles.
AB  - A new class of mono and bis heterocycles-styrylsulfonylmethyl 1,3,4-oxadiazoles,
      pyrazolyl/isoxazolyl-1,3,4-oxadiazoles were prepared and studied their
      antioxidant activity. The compound methyl substituted 2-(p-methylphenylamino
      sulfonylmethyl)-5-[Z-(p-methylstyrylsulfonylmethyl)]-1,3,4-oxadiazole displayed
      slightly higher antioxidant activity than the standard ascorbic acid. 

PMID- 24292791
TI  - Facile preparation of dehydrodigallic acid and its derivative for the synthesis
      of ellagitannins.
AB  - A facile method for the synthesis of dehydrodigallic acid, which is a fundamental
      structure of ellagitannins, was developed. A classical Ullmann condition was
      effective for the formation of the highly hindered biaryl ether structure, and we
      clarified that the suitable protection of the phenolic hydroxy groups was crucial
      in this reaction. In this way, the synthesis of dehydrodigallic acid and its
      derivative was successfully performed. The described method would provide a
      synthetic utility toward ellagitannins. 

PMID- 24292792
TI  - Human dendritic cells derived from embryonic stem cells stably modified with CD1d
      efficiently stimulate antitumor invariant natural killer T cell response.
AB  - Invariant natural killer T (iNKT) cells are a unique lymphocyte subpopulation
      that mediates antitumor activities upon activation. A current strategy to harness
      iNKT cells for cancer treatment is endogenous iNKT cell activation using patient
      derived dendritic cells (DCs). However, the limited number and functional defects
      of patient DCs are still the major challenges for this therapeutic approach. In
      this study, we investigated whether human embryonic stem cells (hESCs) with an
      ectopically expressed CD1d gene could be exploited to address this issue. Using a
      lentivector carrying an optimized expression cassette, we generated stably
      modified hESC lines that consistently overexpressed CD1d. These modified hESC
      lines were able to differentiate into DCs as efficiently as the parental line.
      Most importantly, more than 50% of such derived DCs were CD1d+. These CD1d
      overexpressing DCs were more efficient in inducing iNKT cell response than those
      without modification, and their ability was comparable to that of DCs generated
      from monocytes of healthy donors. The iNKT cells expanded by the CD1d
      overexpressing DCs were functional, as demonstrated by their ability to lyse iNKT
      cell-sensitive glioma cells. Therefore, hESCs stably modified with the CD1d gene
      may serve as a convenient, unlimited, and competent DC source for iNKT cell-based
      cancer immunotherapy. 

PMID- 24292793
TI  - Generation of functional insulin-producing cells from mouse embryonic stem cells
      through 804G cell-derived extracellular matrix and protein transduction of
      transcription factors.
AB  - Embryonic stem (ES) and induced pluripotent stem (iPS) cells have potential
      applications to regenerative medicine for diabetes; however, a useful and safe
      way to generate pancreatic beta cells has not been developed. In this study, we
      tried to establish an effective method of differentiation through the protein
      transduction of three transcription factors (Pdx1, NeuroD, and MafA) important to
      pancreatic beta cell development. The method poses no risk of unexpected genetic
      modifications in target cells. Transduction of the three proteins induced the
      differentiation of mouse ES and mouse iPS cells into insulin-producing cells.
      Furthermore, a laminin-5-rich extracellular matrix efficiently induced
      differentiation under feeder-free conditions. Cell differentiation was confirmed
      with the expression of the insulin 1 gene in addition to marker genes in
      pancreatic beta cells, the differentiated cells secreted glucose-responsive C
      peptide, and their transplantation restored normoglycemia in diabetic mice.
      Moreover, Pdx1 protein transduction had facilitative effects on differentiation
      into pancreatic endocrine progenitors from human iPS cells. These results suggest
      the direct delivery of recombinant proteins and treatment with laminin-5-rich
      extracellular matrix to be useful for the generation of insulin-producing cells. 

PMID- 24292794
TI  - Moving beyond surrogate endpoints in cell therapy trials for heart disease.
AB  - Cell therapy for heart disease began clinically more than a decade ago. Since
      then, numerous trials have been performed, but the studies have been
      underpowered, focusing primarily on low-risk patients with a recent myocardial
      infarction. Many data have accumulated on surrogate endpoints such as ejection
      fraction, but few clinical conclusions can be drawn from such studies. We argue
      here that the time is right for targeting larger and/or higher-risk populations
      for whom there is some expectation of being able to influence mortality or
      rehospitalization. 

PMID- 24292795
TI  - Senescence in cell oxidative status in two bird species with contrasting life
      expectancy.
AB  - Oxidative stress occurs when the production of reactive oxygen species (ROS) by
      an organism exceeds its capacity to mitigate the damaging effects of the ROS.
      Consequently, oxidative stress hypotheses of ageing argue that a decline in
      fecundity and an increase in the likelihood of death with advancing age reported
      at the organism level are driven by gradual disruption of the oxidative balance
      at the cellular level. Here, we measured erythrocyte resistance to oxidative
      stress in the same individuals over several years in two free-living bird species
      with contrasting life expectancy, the great tit (known maximum life expectancy is
      15.4 years) and the Alpine swift (26 years). In both species, we found evidence
      for senescence in cell resistance to oxidative stress, with patterns of
      senescence becoming apparent as subjects get older. In the Alpine swift, there
      was also evidence for positive selection on cell resistance to oxidative stress,
      the more resistant subjects being longer lived. The present findings of inter
      individual selection and intra-individual deterioration in cell oxidative status
      at old age in free-living animals support a role for oxidative stress in the
      ageing of wild animals.

PMID- 24292796
TI  - Informed renesting decisions: the effect of nest predation risk.
AB  - Animals should cue on information that predicts reproductive success. After
      failure of an initial reproductive attempt, decisions on whether or not to
      initiate a second reproductive attempt may be affected by individual experience
      and social information. If the prospects of breeding success are poor, long-lived
      animals in particular should not invest in current reproductive success (CRS) in
      case it generates costs to future reproductive success (FRS). In birds, predation
      risk experienced during breeding may provide a cue for renesting success. Species
      having a high FRS potential should be flexible and take predation risk into
      account in their renesting decisions. We tested this prediction using breeding
      data of a long-lived wader, the southern dunlin Calidris alpina schinzii. As
      predicted, dunlin cued on predation risk information acquired from direct
      experience of nest failure due to predation and ambient nest predation risk.
      While the overall renesting rate was low (34.5%), the early season renesting rate
      was high but declined with season, indicating probable temporal changes in the
      costs and benefits of renesting. We develop a conceptual cost-benefit model to
      describe the effects of the phase and the length of breeding season on predation
      risk responses in renesting. We suggest that species investing in FRS should not
      continue breeding in short breeding seasons in response to predation risk but
      without time constraints, their response should be similar to species investing
      in CRS, e.g. within-season dispersal and increased nest concealment.

PMID- 24292797
TI  - Elastase, alpha1-proteinase inhibitor, and interleukin-8 in children and young
      adults with end-stage kidney disease undergoing continuous ambulatory peritoneal
      dialysis.
AB  - Peritoneal dialysis is one of the main modality of treatment in end-stage kidney
      diseases (ESKD) in children. In our previous work in chronic kidney disease
      patients, in pre-dialyzed period and on hemodialysis, the neutrophils were highly
      activated. The aim of this study was to assess an inflammatory condition and
      neutrophil activation in ESKD patients undergoing continuous ambulatory
      peritoneal dialysis (CAPD). Thirteen CAPD patients without infection, both sexes,
      aged 2.5-24 years, and group of healthy subjects (C) were studied. For
      comparative purposes the conservatively treated (CT) group of ESKD patients was
      included. Neutrophil elastase in complex with alpha1-proteinase inhibitor (NE
      alpha1PI; ELISA), alpha1-proteinase inhibitor (alpha1PI; radial immunodiffusion)
      and interleukin-8 (IL-8; ELISA) were measured in the blood samples from CAPD, CT,
      and C group and in the peritoneal dialysate fluid (PDF) samples of patients on
      CAPD. A significantly increased plasma NE-alpha1PI levels (median 176.5 MUg/L,
      range 85.2-373.2 MUg/L; p < 0.00005), serum IL-8 (median 18.6 pg/mL, range 15.73
      35.28 pg/mL; p < 0.05), and slightly decreased serum alpha1PI (median 1,540 mg/L,
      range 1,270-1,955; p <= 0.05) compared to the control groups were found. There
      were no significant differences of analyzed parameters between CAPD and CT
      patients. The concentration ratio of NE-alpha1PI, alpha1PI and IL-8 in blood/PDF
      was 29.97, 8.24, and 4.48, respectively. There were significantly positive
      correlations between serum and PDF concentration of alpha1PI and IL-8 (r = 0.613,
      p < 0.05; r = 0.59; p < 0.005, respectively). The results of our study
      demonstrate that neutrophils are highly activated in non-infected CAPD patients.
      The pivotal marker of this activation is NE-alpha1PI. It may contribute to
      chronic inflammation and tissues injury.

PMID- 24292799
TI  - Role of vascular endothelial growth factor (VEGF) in the neurological
      manifestations of dengue: a preliminary study.
AB  - This study reports on vascular endothelial growth factor (VEGF) in dengue
      patients with neurological manifestations. Their bleeding diathesis, hypotension,
      edema, flushing, and hepatosplenomegaly were noted. Complete blood counts, serum
      chemistry, coagulation profile, liver and kidney function tests, creatine kinase
      (CK), and MRI in encephalopathic patients were carried out. Serum VEGF was
      estimated by ELISA in 21 dengue patients and 14 controls. Twelve patients had
      dengue fever (DF), eight dengue hemorrhagic fever (DHF), and one dengue shock
      syndrome (DSS). Fifteen patients had neurological manifestation, 12 had muscle
      involvement (raised CK with or without weakness), and 3 had encephalopathy. The
      VEGF level in dengue patients was 50.0 +/- 56.1 pg/mL and in the controls, 60.6
      +/- 20.3 pg/mL. The VEGF level neither correlated with the severity nor with the
      neurological involvement. Thrombocytopenia, however, correlated with the severity
      of dengue and neurological manifestations. The VEGF level is not related to the
      severity of dengue and neurological syndrome.

PMID- 24292798
TI  - Diverse roles of natural killer T lymphocytes in liver and spleen in mice with
      experimental autoimmune uveitis.
AB  - Natural killer T lymphocytes (NKT cells) have diverse roles in different organs.
      However, it is still unclear whether NKT cells play different roles in the liver
      and spleen in mice with experimental autoimmune uveitis. In the present study, we
      explored their diverse roles of NKT cells in the liver and spleen and found that
      liver-derived NKT cells could efficiently inhibit Th1 and Th17 differentiation,
      whereas the function of spleen-derived NKT cells was less potent. Meanwhile, the
      occurrence of the peak ratios of NKT cells/T cells in the spleen and liver was
      markedly asynchronous after immunization. Moreover, different methods of
      immunization could result in different immune responses in mice. Furthermore, the
      memory response was also found in the generation of NKT cells in mice when they
      received the same antigen. These results indicate that the functional roles of
      NKT cells possess diversity in the spleen and liver in mice with experimental
      autoimmune uveitis. 

PMID- 24292800
TI  - Inflammatory mediators as biomarkers in brain disorders.
AB  - Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral
      sclerosis, and Huntington are incurable and debilitating conditions that result
      in progressive death of the neurons. The definite diagnosis of a
      neurodegenerative disorder is disadvantaged by the difficulty in obtaining
      biopsies and thereby to validate the clinical diagnosis with pathological
      results. Biomarkers are valuable indicators for detecting different phases of a
      disease such as prevention, early onset, treatment, progression, and monitoring
      the effect of pharmacological responses to a therapeutic intervention.
      Inflammation occurs in neurodegenerative diseases, and identification and
      validation of molecules involved in this process could be a strategy for finding
      new biomarkers. The ideal inflammatory biomarker needs to be easily measurable,
      must be reproducible, not subject to wide variation in the population, and
      unaffected by external factors. Our review summarizes the most important
      inflammation biomarkers currently available, whose specificity could be utilized
      for identifying and monitoring distinctive phases of different neurodegenerative
      diseases. 

PMID- 24292801
TI  - The relationship between serum lipoprotein (a) levels and ischemic stroke risk: a
      cohort study in the Chinese population.
AB  - The role of atherosclerosis in ischemic stroke has been intensively investigated
      in recent years, and lipoprotein (a) [Lp(a)] is found to have roles during the
      process. The aim of this study was to investigate the relationship between acute
      ischemic stroke (AIS) and serum Lp(a) levels in the Chinese population. All
      consecutive patients with first-ever acute ischemic stroke during 2011-2012 were
      recruited to participate in the study. Serum Lp(a) levels and routine tests were
      examined in both groups. The National Institutes of Health Stroke Scale (NIHSS)
      score was assessed on admission blinded to Lp(a) levels. In this study, 181
      patients with acute ischemic stroke were included. There was a significant
      difference in median serum Lp(a) levels between acute ischemic stroke patients
      and control cases (328 [IQR, 173-554] vs. 145 [IQR, 66-254] mg/L, respectively; P
      = 0.000). Lp(a) levels increased with increasing severity of stroke as defined by
      the NIHSS score (P = 0.000). For the entire group, when adjusting for other
      possible risk factors, an elevated Lp(a) level was an independent risk factor for
      stroke, and a serum Lp(a) level >=300 mg/L was associated with a 2.23-fold
      increase in AIS (P = 0.015). In addition, this association was stronger in male
      than in female patients. High Lp(a) levels are significantly related to stroke,
      independent from other traditional and emerging risk factors, suggesting that
      they may play a role in its pathogenesis. It should be considered as a routine
      risk factor for stroke in the Chinese population. 

PMID- 24292804
TI  - Verification of radiocesium decontamination from farmlands by plants in
      Fukushima.
AB  - The purpose of this study was to verify radiocesium decontamination from
      Fukushima farmland by plants and to screen plants useful for phytoremediation.
      Thirteen species from three families (Asteraceae, Fabaceae, and Poaceae) of crops
      were grown in shallow and deeply cultivated fields (0-8 and 0-15 cm plowing,
      respectively). To change plowing depth was expected to make different contacting
      zone between root system and radiocesium in soil. The radioactivity values of the
      plants due to the radiocesium 134Cs and 137Cs were 22-179 and 29-225 Bq kg dry
      weight-1, respectively. The 134Cs and 137Cs transfer factors for plants grown in
      the shallow field ranged from 0.021 to 0.12 and fro 0.019 to 0.13, respectively,
      with the geometric means of 0.051 and 0.057, respectively. The 134Cs and 137Cs
      transfer factors for plants grown in the deep field ranged from 0.019 to 0.13 and
      from 0.022 to 0.13, respectively, with the geometric means of 0.045 and 0.063,
      respectively. Although a reducing ratio was calculated to evaluate the decrease
      in radiocesium from contaminated soil during cultivation (i.e., phytoremediation
      ability), no plant species resulted in a remarkable decrease in radiocesium in
      soil among the tested crops. These results should be followed up for several
      years and further analyses are required to evaluate whether the phytoremediation
      technique is applicable to radioactively contaminated farmlands.

PMID- 24292805
TI  - Duodenal haematoma following endoscopy as a marker of coagulopathy.
AB  - BACKGROUND: Intramural duodenal haematomas (IDHs) are a rare complication of
      endoscopic biopsy but can cause significant morbidity and mortality, including
      duodenal obstruction, hospitalization and needing intravenous feeding. They are
      extremely uncommon in those with normal haematology. OBJECTIVE: To describe the
      occurrence of IDHs following endoscopic biopsy in our institution. MATERIALS AND
      METHODS: We identified three patients who developed a post biopsy IDH during an
      18-month period (2010-2012) in a retrospective search of our hospital pathology
      and imaging databases. RESULTS: All three children had complex medical problems
      and presented with gastrointestinal symptoms including severe abdominal pain,
      reflux, poor feeding and abnormal gut transit time. All underwent normal upper GI
      endoscopy with duodenal biopsy. Following endoscopy, they presented with
      intermittent GI obstruction with severe abdominal pain, distension and bilious
      vomiting or symptoms of pancreatitis, had imaging features of IDH and were
      managed conservatively making a full recovery. Initial haematology including
      platelet counts were normal, but two children were subsequently found to have
      platelet dysfunction and the third to have an unclassified coagulopathy.
      CONCLUSION: IDHs may be the presenting factor in children with unsuspected
      bleeding problems. We present these findings to raise awareness of the imaging
      features and clinical impact of these cases because better understanding of these
      risk factors may help to avoid these complications in children in the future.

PMID- 24292806
TI  - Metabolic syndrome and associated factors in people with chronic obstructive
      pulmonary disease.
AB  - The prevalence of metabolic syndrome (MetS) in people with chronic obstructive
      pulmonary disease (COPD) varies in European and Asian countries and does not
      always mirror the prevalence of the general population in a given country. We
      compared the prevalence of MetS in people with COPD with a comparison group in
      the United States. The National Health and Nutrition Evaluation Survey data set
      (2007-2010) was used to identify 94 people with COPD (mean age = 62). Data for
      demographic and clinical characteristics were obtained by interview and physical
      examination. Descriptive and inferential statistics were used to analyze the
      data. The prevalence of MetS was 57.5% in the COPD group and 53.6% in the
      comparison group. In people with COPD, the factors most significantly associated
      with MetS were age, income level, marital status, and respiratory symptoms.
      People with COPD should be screened for MetS. 

PMID- 24292807
TI  - Clinical significance of STA-MCA double anastomosis for hemodynamic compromise in
      post-JET/COSS era.
AB  - BACKGROUND: Even after the recent randomized clinical trials JET and COSS, it is
      still unclear that impaired cerebrovascular reactivity (CVR) to acetazolamide and
      oxygen extraction fraction (OEF) can identify the candidates for superficial
      temporal artery to middle cerebral artery (STA-MCA) anastomosis. This prospective
      study was aimed to evaluate the benefits of STA-MCA "double" anastomosis on long
      term outcome in patients with reduced cerebral blood flow (CBF) and CVR (Type 3
      ischemia) and elevated OEF attributable to occlusive carotid diseases. METHODS:
      This study included 49 patients with reduced CBF and CVR on SPECT in the
      ipsilateral MCA area. Using (15)O-gas PET, OEF was also measured in all patients.
      STA-MCA double anastomosis was recommended to the patients with Type 3 and
      elevated OEF. Those with Type 3 but normal OEF were medically treated. RESULTS:
      Of 36 patients with Type 3 and elevated OEF, 25 consented to surgery. No
      perioperative morbidity or mortality were noted. The other 11 patients with Type
      3 and elevated OEF were medically treated. Annual incidence of ipsilateral stroke
      was 0.7% and 6.5% in surgically and medically treated patients with Type 3 and
      elevated OEF, respectively (P = 0.0188). None of patients with Type 3 but normal
      OEF developed ipsilateral stroke during follow-up periods. STA-MCA "double"
      anastomosis significantly decreased OEF. CONCLUSIONS: STA-MCA "double"
      anastomosis may still have the potential to reduce the risk of recurrent
      ipsilateral stroke in hemodynamically compromised patients. Further studies would
      be essential to advance diagnosis, surgical procedures, and perioperative
      managements to bring out maximal effects of bypass surgery.

PMID- 24292808
TI  - Comparative outcomes of ulnar nerve transposition versus neurolysis in patients
      with entrapment neuropathy at the cubital tunnel: a 20-year analysis.
AB  - BACKGROUND: Entrapment neuropathy of the ulnar nerve at the level of the elbow is
      the shared domain of multiple surgical specialties. A wide variety of operative
      methods for its surgical management have been reported. Our hospital utilizes
      neurolysis (NL) and subcutaneous transposition (AST). The aim of this paper was
      to compare the clinical outcomes in patients treated by ulnar nerve transposition
      versus neurolysis over a 20-year period. METHODS: We included patients who
      underwent either neurolysis or an ulnar nerve transposition. A retrospective
      analysis was performed which included 480 patients at our institution between
      January 1992 and December 2012. In total, physical and electronic records for 480
      patients were reviewed. Three-hundred and one underwent ulnar nerve transposition
      and 179 underwent ulnar nerve neurolysis . RESULTS: In the AST group 201/301
      patients suffered from parasthesiae pre-operatively and 156/301 had pain at and
      around the cubital tunnel. Paresis of the ulnar nerve innervated muscles was
      present in 99/301 patients. At the 3-month follow-up appointment, 187/201
      patients with parasthesiae and 113/156 patients with local pain had resolution of
      their symptoms. In the NL group 151/179 patients had parasthesiae pre-operatively
      and 126/179 had pain at and around the cubital tunnel. Paresis of the ulnar nerve
      innervated muscles was present in 56/179 patients. At the 3-month follow-up
      appointment, 141/151 patients with parasthesiae and 117/126 patients with local
      pain had resolution of their symptoms. CONCLUSIONS: In cases of ulnar nerve
      compression at the cubital tunnel, both neurolysis and transposition are
      effective in improving clinical outcome. The only statistically significant
      advantage of neurolysis over transposition seems to be relief of localized elbow
      pain. We recommend neurolysis as the preferred procedure.

PMID- 24292810
TI  - Integrative approaches to safeguarding the health and safety of workers.

PMID- 24292809
TI  - Prevalence of rheumatoid arthritis in Serbia.
AB  - The aim of this study was to estimate the prevalence of rheumatoid arthritis (RA)
      in Serbia, using the European EULAR project methodology. In a detection phase, a
      previously translated and validated telephone Questionnaire was used by lay
      interviewers on 6,213 randomly selected telephone numbers representing urban
      population from four Serbian towns: Belgrade (north), Cacak, Uzice and Krusevac
      (south). Patients with suspected RA were called again by a rheumatologist. For
      patients with self-reported diagnosis and positive symptoms, patient's
      rheumatologist was contacted to confirm diagnosis; a complete rheumatologist
      examination was scheduled for those with positive symptoms only. Prevalence
      estimates were standardised for age and sex in relation to Serbian population
      (census 2002) and further to French population, according to EULAR project
      methodology. The response rate was 63.6 % (3,950 respondents). The rheumatologist
      called 571 people, among whom 23 RA cases were confirmed (21 diagnosed previously
      and 2 newly diagnosed during the examination). The prevalence was 0.16 % (95 %
      confidence interval CI 0.01-0.32) for men and 0.51 % (95 % CI 0.26-0.76) for
      women; a female-to-male ratio 3.18. The overall Serbian standardised prevalence
      was 0.35 % (95 % CI 0.18-0.52); when standardised on French population 0.34 % (95
      % CI 0.17-0.51). The highest age-specific rate was in the 65-74-year age band.
      The EULAR prevalence study, conducted with similar methodology and design, showed
      that RA prevalence estimates in Serbia (0.34 %) were in accordance with France
      (0.31 %), but lower than in Lithuania (0.55 %). 

PMID- 24292811
TI  - Tumor suppressor functions of Dnmt3a and Dnmt3b in the prevention of malignant
      mouse lymphopoiesis.

PMID- 24292812
TI  - Proton transfer and hydrogen bonding in the organic solid state: a combined
      XRD/XPS/ssNMR study of 17 organic acid-base complexes.
AB  - The properties of nitrogen centres acting either as hydrogen-bond or Bronsted
      acceptors in solid molecular acid-base complexes have been probed by N 1s X-ray
      photoelectron spectroscopy (XPS) as well as (15)N solid-state nuclear magnetic
      resonance (ssNMR) spectroscopy and are interpreted with reference to local
      crystallographic structure information provided by X-ray diffraction (XRD). We
      have previously shown that the strong chemical shift of the N 1s binding energy
      associated with the protonation of nitrogen centres unequivocally distinguishes
      protonated (salt) from hydrogen-bonded (co-crystal) nitrogen species. This result
      is further supported by significant ssNMR shifts to low frequency, which occur
      with proton transfer from the acid to the base component. Generally, only minor
      chemical shifts occur upon co-crystal formation, unless a strong hydrogen bond is
      formed. CASTEP density functional theory (DFT) calculations of (15)N ssNMR
      isotropic chemical shifts correlate well with the experimental data, confirming
      that computational predictions of H-bond strengths and associated ssNMR chemical
      shifts allow the identification of salt and co-crystal structures (NMR
      crystallography). The excellent agreement between the conclusions drawn by XPS
      and the combined CASTEP/ssNMR investigations opens up a reliable avenue for local
      structure characterization in molecular systems even in the absence of crystal
      structure information, for example for non-crystalline or amorphous matter. The
      range of 17 different systems investigated in this study demonstrates the generic
      nature of this approach, which will be applicable to many other molecular
      materials in organic, physical, and materials chemistry. 

PMID- 24292814
TI  - DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation
      and doxorubicin.
AB  - DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA
      double-strand breaks (DSBs) that are probably the most deleterious form of DNA
      damage. Inhibition of DNA-PK has been considered as an attractive approach to
      decrease resistance to therapeutically induced DNA DSBs. Ionizing radiation (IR)
      and doxorubicin, which induce DSBs, are used in the treatment of breast cancer.
      We determined the cellular concentration of DNA-PK and other DSB-activated
      kinases: ATM and ATR and the effect of DNA-PK inhibition by NU7441 on DNA repair,
      cell cycle, and survival after IR or doxorubicin treatment in three human breast
      cancer cell lines (MCF-7, MDA-MB-231, and T47D) representing different breast
      cancer subtypes. T47D cells had the highest expression of DNA-PKcs, ATM, and ATR
      and the most rapid rate of DNA DSB repair. IR caused a 10- to 16-fold increase in
      DNA-PK activity and two to threefold induction of ATM in all 3 cell lines. NU7441
      inhibited IR-induced DNA-PK activity in all cell lines with IC50s in the range
      0.17-0.25 MUM. NU7441 retarded the repair of DSB and significantly increased the
      sensitivity of all cell lines to IR (4- to 12-fold) and doxorubicin (3- to 13
      fold). The greatest sensitization by NU7441 was observed in MDA-MB-231 cells.
      NU7441 affected the cell cycle distribution in all studied cell lines; increasing
      accumulation of cells in G2/M phase after DNA damage. Our data indicate that DNA
      PK might be an effective target for chemo- and radio-potentiation in breast
      cancer and suggest that further development of DNA-PK inhibitors for clinical use
      is warranted.

PMID- 24292813
TI  - Characterizing the heterogeneity of triple-negative breast cancers using
      microdissected normal ductal epithelium and RNA-sequencing.
AB  - Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined
      by an absence of actionable therapeutic targets (ER, PR, and HER-2).
      Microdissected normal ductal epithelium from healthy volunteers represents a
      novel comparator to reveal insights into TNBC heterogeneity and to inform drug
      development. Using RNA-sequencing data from our institution and The Cancer Genome
      Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal
      breast tissues from healthy volunteers from the Susan G. Komen for the Cure
      Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway
      analysis comparing TNBCs to optimized normal controls of microdissected normal
      epithelium versus classic controls composed of adjacent normal tissue revealed
      distinct molecular signatures. Differential gene expression of TNBC compared with
      normal comparators demonstrated important findings for TNBC-specific clinical
      trials testing targeted agents; lack of over-expression for negative studies and
      over-expression in studies with drug activity. Next, by comparing each individual
      TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity
      is attributable to transcriptional chaos, is associated with non-silent DNA
      mutational load, and explains transcriptional heterogeneity in addition to known
      molecular subtypes. Finally, chaos analysis identified 146 core genes
      dysregulated in >90 % of TNBCs revealing an over-expressed central network. In
      conclusion, use of microdissected normal ductal epithelium from healthy
      volunteers enables an optimized approach for studying TNBC and uncovers
      biological heterogeneity mediated by transcriptional chaos. 

PMID- 24292815
TI  - Superior outcome after neoadjuvant chemotherapy with docetaxel, anthracycline,
      and cyclophosphamide versus docetaxel plus cyclophosphamide: results from the
      NATT trial in triple negative or HER2 positive breast cancer.
AB  - The purpose of this study is to evaluate the efficacy and safety of docetaxel
      plus cyclophosphamide(TC) compared with docetaxel, anthracycline, and
      cyclophosphamide(TEC) in neoadjuvant treatment of triple negative or HER2
      positive breast cancer. Eligible breast cancer patients were randomized to
      receive six cycles of TC or TEC. The primary end point was pathological complete
      remission (pCR). Secondary end points included safety, clinical response rate,
      and survival outcome. One hundred and two patients were initially randomized and
      96 patients were available for efficacy analysis. 96.9 % patients were treated
      with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 %
      (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20
      (3-36) months, non-anthracycline-containing TC regimen treatment resulted in a
      worse event free survival (adjusted hazard ratio [HR] 2.42; 95 % CI1.11-5.30) and
      disease-free survival (HR 2.85; 95 % CI1.21-6.74) compared with TEC regimen,
      which was more apparent in triple negative subtype. Severe adverse event rates
      were similar, except that patients treated with TEC had a higher rate of
      neutropenia and leucopenia. TEC treatment had a superior survival outcome and
      trend of higher pCR rate compared with TC in this trial setting, especially in
      triple negative subtype, which deserves further validation.

PMID- 24292816
TI  - Multiscale immunomagnetic enrichment of circulating tumor cells: from tubes to
      microchips.
AB  - We review the rare cancer cell sorting technologies, with a focus on multiscale
      immunomagnetic approaches. Starting from the conventional magnetic activated cell
      sorting system, we derive the scaling laws of immunomagnetic assay and justify
      the recent trend of using downscaled systems for CTC studies. Furthermore, we
      introduce recent work on combining the immunomagnetic assay with microfluidic
      technology for enhanced separation. We summarize different types of in-channel
      micro-magnetic structures that can further increase the local magnetic field
      without lowering the system throughput. Related design concepts, principles, and
      microfabrication techniques are presented and evaluated. 

PMID- 24292817
TI  - Looking above the prairie: localized and upward acute vision in a native
      grassland bird.
AB  - Visual systems of open habitat vertebrates are predicted to have a band of acute
      vision across the retina (visual streak) and wide visual coverage to gather
      information along the horizon. We tested whether the eastern meadowlark
      (Sturnella magna) had this visual configuration given that it inhabits open
      grasslands. Contrary to our expectations, the meadowlark retina has a localized
      spot of acute vision (fovea) and relatively narrow visual coverage. The fovea
      projects above rather than towards the horizon with the head at rest, and
      individuals modify their body posture in tall grass to maintain a similar foveal
      projection. Meadowlarks have relatively large binocular fields and can see their
      bill tips, which may help with their probe-foraging technique. Overall,
      meadowlark vision does not fit the profile of vertebrates living in open
      habitats. The binocular field may control foraging while the fovea may be used
      for detecting and tracking aerial stimuli (predators, conspecifics). 

PMID- 24292818
TI  - Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm
      infants until 6 months post-term.
AB  - PURPOSE: An iron intake of >2 mg/kg/d is recommended for preterm infants. We
      hypothesized that human milk (HM)-fed preterm infants require iron
      supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8-1.0 mg
      iron/100 ml) may provide sufficient dietary iron until 6 months post-term.
      METHODS: At term age, 3 and 6 months post-term, ferritin (MUg/l) was measured in
      92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4)
      weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0
      (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term
      age and 6 months post-term was calculated. RESULTS: Iron was supplemented to
      71.7% of HM-fed and 83.7% of IFF-fed infants between term age and 3 months post
      term and to 13% of HM-fed and 0% of IFF-fed infants between 3 and 6 months post
      term. IFF-fed infants had an iron intake from supplements and formula of 2.66
      (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d
      between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of
      ferritin <12 MUg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs.
      7.8% and 26.3 vs. 9.5%, P < 0.02). CONCLUSION: This observational study
      demonstrates that ferritin <12 MUg/l is more prevalent in HM-fed infants until 6
      months post-term. This may be due to early cessation of additional iron
      supplementation. We speculate that additional iron supplementation is not
      necessary in preterm infants fed IFF (0.8-1.0 mg iron/100 ml), as they achieve
      ferritin >=12 MUg/l without additional iron supplements between 3 and 6 months
      post-term.

PMID- 24292819
TI  - Frequencies and demographic determinants of breastfeeding and DHA supplementation
      in a nationwide sample of mothers in Germany.
AB  - PURPOSE: German guidelines recommend breast milk as ideal for infant's nutrition,
      supporting exclusive breastfeeding for at least 4 months. Moreover, in mothers
      with insufficient fish intake, DHA status may be improved by supplementation
      during pregnancy and lactation. However, little is known on current rates of
      breastfeeding and DHA supplementation in Germany. The objective of this study was
      to analyse frequencies and demographic determinants of breastfeeding and DHA
      supplementation in Germany. METHODS: Data derived from a nationwide consumer
      survey of 986 mothers with children between 5 and 36 months of age in Germany.
      RESULTS: 78.3% reported that they ever breastfed their children, and 55.6% of the
      mothers exclusively breastfed for at least 4 months. Mothers who did not
      breastfeed were less likely to be informed by their paediatrician or midwife and
      were more often not informed at all; 27.8% of mothers used DHA supplements during
      pregnancy, 16.8% postnatal. DHA supplementation was more common in women with a
      high versus a low fish intake. The social status was the major determinant of
      breastfeeding initiation and exclusivity and also DHA supplementation.
      CONCLUSION: Breastfeeding initiation and duration of exclusive breastfeeding in
      Germany need to be improved. Professional counselling and support, with a focus
      on mothers from lower social classes, appears necessary to increase current rates
      of breastfeeding initiation, duration, and exclusiveness, but also to ensure a
      sufficient supply with DHA in pregnant and lactating women, particularly in women
      with low fish consumption.

PMID- 24292820
TI  - Vitamin D supplementation, body weight and human serum 25-hydroxyvitamin D
      response: a systematic review.
AB  - PURPOSE: There is considerable variation in incremental circulating 25
      hydroxyvitamin D (25OHD) levels on vitamin D supplements, even when similar age
      groups and identical vitamin D doses are compared. We therefore aimed to
      investigate the importance of body weight for the dose-response relation in
      circulating 25OHD. METHODS: We performed a systematic review of randomized
      placebo-controlled vitamin D supplementation trials in all age groups >=10 years
      to clarify the influence of body weight and other parameters on incremental
      circulating 25OHD levels (difference between baseline and in-study values) in
      vitamin D-deficient and non-deficient individuals. RESULTS: We included 144
      cohorts from 94 independent studies, published from 1990 to November 2012, in our
      systematic review. There was a logarithmic association between vitamin D dose per
      kg body weight per day and increment in circulating 25OHD. In multivariable
      regression analysis, vitamin D dose per kg body weight per day could explain
      34.5% of variation in circulating 25OHD. Additional significant predictors were
      type of supplement (vitamin D2 or vitamin D3), age, concomitant intake of calcium
      supplements and baseline 25OHD, explaining 9.8, 3.7, 2.4 and 1.9%, respectively,
      of the variation in circulating 25OHD. CONCLUSIONS: This systematic review
      demonstrates that body weight is an important predictor of variation in
      circulating 25OHD in cohorts on vitamin D supplements. Our model provides an
      estimate of the daily vitamin D dose that is necessary for achieving adequate
      circulating 25OHD levels in vitamin D-insufficient or vitamin D-deficient
      individuals/cohorts with different body weights and ages.

PMID- 24292821
TI  - A comparison of the incidence of hypercapnea in non-obese and morbidly obese peri
      operative patients using the SenTec transcutaneous pCO(2) monitor.
AB  - Obese patients are at increased risk for hypoventilation, leading to hypercapnea
      and acidosis. The primary objective of this study was to compare the incidence of
      perioperative hypercapnea in non-obese and morbidly obese patients using the
      SenTec transcutaneous PCO2 (tcPCO2) monitor. 10 morbidly obese subjects (BMI > 40
      kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 non-obese subjects
      (BMI < 30 kg/m(2)) undergoing laparoscopic abdominal procedures were studied,
      using a standardized anesthesia regimen. TcPCO2 and SpO2 were monitored
      continuously intraoperatively, and during the first 24 h postoperatively. Opiate
      consumption, respiratory rate (RR), and pain scores were collected from
      postanesthesia care unit (PACU) and ward nursing notes. RR, SpO2, and tcPCO2 did
      not differ significantly between groups during PACU or ward time periods. End
      tidal CO2 (EtCO2) values were similar between groups during the intraoperative
      period, but tcPCO2 was significantly higher in the obese group at specific time
      points, and trended towards being higher throughout the case. Our study did not
      show significant tcPCO2 differences between non-obese and obese post-surgical
      patients, however, it did allow for continuous, trendable, nonobtrusive
      monitoring throughout the perioperative period. As V/Q mismatch increases with
      the PaCO2/EtCO2 gradient, and this effect is most pronounced in morbidly obese
      patients, tcPCO2 monitoring may prove to be a useful additional monitor in these
      patients during the intraoperative period. 

PMID- 24292823
TI  - Arrestin interactions with G protein-coupled receptors.
AB  - G-protein-coupled receptors (GPCRs) are the primary interaction partners for
      arrestins. The visual arrestins, arrestin1 and arrestin4, physiologically bind to
      only very few receptors, i.e., rhodopsin and the color opsins, respectively. In
      contrast, the ubiquitously expressed nonvisual variants beta-arrestin1 and 2 bind
      to a large number of receptors in a fairly nonspecific manner. This binding
      requires two triggers, agonist activation and receptor phosphorylation by a G
      protein-coupled receptor kinase (GRK). These two triggers are mediated by two
      different regions of the arrestins, the "phosphorylation sensor" in the core of
      the protein and a less well-defined "activation sensor." Binding appears to occur
      mostly in a 1:1 stoichiometry, involving the N-terminal domain of GPCRs, but in
      addition a second GPCR may loosely bind to the C-terminal domain when active
      receptors are abundant.Arrestin binding initially uncouples GPCRs from their G
      proteins. It stabilizes receptors in an active conformation and also induces a
      conformational change in the arrestins that involves a rotation of the two
      domains relative to each other plus changes in the polar core. This
      conformational change appears to permit the interaction with further downstream
      proteins. The latter interaction, demonstrated mostly for beta-arrestins,
      triggers receptor internalization as well as a number of nonclassical signaling
      pathways.Open questions concern the exact stoichiometry of the interaction,
      possible specificity with regard to the type of agonist and of GRK involved,
      selective regulation of downstream signaling (=biased signaling), and the options
      to use these mechanisms as therapeutic targets.

PMID- 24292822
TI  - Therapeutic potential of small molecules and engineered proteins.
AB  - Virtually all currently used therapeutic agents are small molecules, largely
      because the development and delivery of small molecule drugs is relatively
      straightforward. Small molecules have serious limitations: drugs of this type can
      be fairly good enzyme inhibitors, receptor ligands, or allosteric modulators.
      However, most cellular functions are mediated by protein interactions with other
      proteins, and targeting protein-protein interactions by small molecules presents
      challenges that are unlikely to be overcome with these compounds as the only
      tools. Recent advances in gene delivery techniques and characterization of cell
      type-specific promoters open the prospect of using reengineered signaling-biased
      proteins as next-generation therapeutics. The first steps in targeted engineering
      of proteins with desired functional characteristics look very promising. As
      quintessential scaffolds that act strictly via interactions with other proteins
      in the cell, arrestins represent a perfect model for the development of these
      novel therapeutic agents with enormous potential: custom-designed signaling
      proteins will allow us to tell the cell what to do and when to do it in a way it
      cannot disobey. 

PMID- 24292824
TI  - Quantifying biased beta-arrestin signaling.
AB  - It is now established that agonists do not uniformly activate pleiotropic
      signaling mechanisms initiated by receptors but rather can bias signals according
      to the unique receptor conformations they stabilize. One of the important
      emerging signaling systems where this can occur is through beta-arrestin. This
      chapter discusses biased signaling where emphasis or de-emphasis of beta-arrestin
      signaling is postulated (or been shown) to be beneficial. The chapter
      specifically focuses on methods to quantify biased effects; these methods furnish
      scales that can be used in the process of optimizing biased agonism (and
      antagonism) for therapeutic benefit. Specifically, methods to derive
      DeltaDeltaLog(tau/K A) or DeltaDeltaLog(Relative Activity) values are described
      to do this. 

PMID- 24292825
TI  - The physiological roles of arrestin-1 in rod photoreceptor cells.
AB  - Arrestin-1 is the second most abundant protein in rod photoreceptors and is
      nearly equimolar to rhodopsin. Its well-recognized role is to "arrest" signaling
      from light-activated, phosphorylated rhodopsin, a prototypical G protein-coupled
      receptor. In doing so, arrestin-1 plays a key role in the rapid recovery of the
      light response. Arrestin-1 exists in a basal conformation that is stabilized by
      two independent sets of intramolecular interactions. The intramolecular
      constraints are disrupted by encountering (1) active conformation of the receptor
      (R*) and (2) receptor-attached phosphates. Requirement for these two events
      ensures its highly specific high-affinity binding to phosphorylated, light
      activated rhodopsin (P-R*). In the dark-adapted state, the basal form is further
      organized into dimers and tetramers. Emerging data suggest pleiotropic roles of
      arrestin-1 beyond the functional range of rod cells. These include light-induced
      arrestin-1 translocation from the inner segment to the outer segment, a process
      that may be protective against cellular damage incurred by constitutive
      signaling. Its expanding list of binding partners also hints at additional, yet
      to be characterized functions. Uncovering these novel roles of arrestin-1 is a
      subject of future studies. 

PMID- 24292826
TI  - Not just signal shutoff: the protective role of arrestin-1 in rod cells.
AB  - The retinal rod cell is an exquisitely sensitive single-photon detector that
      primarily functions in dim light (e.g., moonlight). However, rod cells must
      routinely survive light intensities more than a billion times greater (e.g.,
      bright daylight). One serious challenge to rod cell survival in daylight is the
      massive amount of all-trans-retinal that is released by Meta II, the light
      activated form of the photoreceptor rhodopsin. All-trans-retinal is toxic, and
      its condensation products have been implicated in disease. Our recent work has
      developed the concept that rod arrestin (arrestin-1), which terminates Meta II
      signaling, has an additional role in protecting rod cells from the consequences
      of bright light by limiting free all-trans-retinal. In this chapter we will
      elaborate upon the molecular mechanisms by which arrestin-1 serves as both a
      single-photon response quencher as well as an instrument of rod cell survival in
      bright light. This discussion will take place within the framework of three
      distinct functional modules of vision: signal transduction, the retinoid cycle,
      and protein translocation. 

PMID- 24292827
TI  - Cone arrestin: deciphering the structure and functions of arrestin 4 in vision.
AB  - Cone arrestin (Arr4) was discovered 20 years ago as a human X-chromosomal gene
      that is highly expressed in pinealocytes and cone photoreceptors. Subsequently,
      specific antibodies were developed to identify Arr4 and to distinguish cone
      photoreceptor morphology in health and disease states. These reagents were used
      to demonstrate Arr4 translocation from cone inner segments in the dark to outer
      segments with light stimulation, similarly to Arrestin 1 (Arr1) translocation in
      rod photoreceptors. A decade later, the Arr4 crystal structure was solved, which
      provided more clues about Arr4's mechanisms of action. With the creation of
      genetically engineered visual arrestin knockout mice, one critical function of
      Arr4 was clarified. In single living cones, both visual arrestins bind to light
      activated, G protein receptor kinase 1 (Grk1) phosphorylated cone opsins to
      desensitize them, and in their absence, mouse cone pigment shutoff is delayed.
      Still under investigation are additional functions; however, it is clear that
      Arr4 has non-opsin-binding partners and diverse synaptic roles, including
      cellular anchoring and trafficking. Recent studies reveal Arr4 is involved in
      high temporal resolution and contrast sensitivity, which opens up a new direction
      for research on this intriguing protein. Even more exciting is the potential for
      therapeutic use of the Arr4 promoter with an AAV-halorhodopsin that was shown to
      be effective in using the remaining cones in retinal degeneration mouse models to
      drive inner retinal circuitry for motion detection and light/dark discrimination.

PMID- 24292828
TI  - Enhanced phosphorylation-independent arrestins and gene therapy.
AB  - A variety of heritable and acquired disorders is associated with excessive
      signaling by mutant or overstimulated GPCRs. Since any conceivable treatment of
      diseases caused by gain-of-function mutations requires gene transfer, one
      possible approach is functional compensation. Several structurally distinct forms
      of enhanced arrestins that bind phosphorylated and even non-phosphorylated active
      GPCRs with much higher affinity than parental wild-type proteins have the ability
      to dampen the signaling by hyperactive GPCR, pushing the balance closer to
      normal. In vivo this approach was so far tested only in rod photoreceptors
      deficient in rhodopsin phosphorylation, where enhanced arrestin improved the
      morphology and light sensitivity of rods, prolonged their survival, and
      accelerated photoresponse recovery. Considering that rods harbor the fastest, as
      well as the most demanding and sensitive GPCR-driven signaling cascade, even
      partial success of functional compensation of defect in rhodopsin phosphorylation
      by enhanced arrestin demonstrates the feasibility of this strategy and its
      therapeutic potential. 

PMID- 24292829
TI  - Targeting individual GPCRs with redesigned nonvisual arrestins.
AB  - Numerous human diseases are caused by excessive signaling of mutant G protein
      coupled receptors (GPCRs) or receptors that are overstimulated due to upstream
      signaling imbalances. The feasibility of functional compensation by arrestins
      with enhanced ability to quench receptor signaling was recently tested in the
      visual system. The results showed that even in this extremely demanding situation
      of rods that have no ability to phosphorylate rhodopsin, enhanced arrestin
      improved rod morphology, light sensitivity, survival, and accelerated
      photoresponse recovery. Structurally distinct enhanced mutants of arrestins that
      bind phosphorylated and non-phosphorylated active GPCRs with much higher affinity
      than parental wild-type (WT) proteins have been constructed. These "super
      arrestins" are likely to have the power to dampen the signaling by hyperactive
      GPCRs. However, most cells express 5-20 GPCR subtypes, only one of which would be
      overactive, while nonvisual arrestins are remarkably promiscuous, binding
      hundreds of different GPCRs. Thus, to be therapeutically useful, enhanced
      versions of nonvisual arrestins must be made fairly specific for particular
      receptors. Recent identification of very few arrestin residues as key receptor
      discriminators paves the way to the construction of receptor subtype-specific
      nonvisual arrestins. 

PMID- 24292830
TI  - beta-arrestins and G protein-coupled receptor trafficking.
AB  - Nonvisual arrestins (beta-arrestin-1 and beta-arrestin-2) are adaptor proteins
      that function to regulate G protein-coupled receptor (GPCR) signaling and
      trafficking. beta-arrestins are ubiquitously expressed and function to inhibit
      GPCR/G protein coupling, a process called desensitization, and promote GPCR
      trafficking and arrestin-mediated signaling. beta-arrestin-mediated endocytosis
      of GPCRs requires the coordinated interaction of beta-arrestins with clathrin,
      adaptor protein 2 (AP2), and phosphoinositides. These interactions are
      facilitated by a conformational change in beta-arrestin that is thought to occur
      upon binding to a phosphorylated activated GPCR. In this review, we provide an
      overview of the key interactions involved in beta-arrestin-mediated trafficking
      of GPCRs. 

PMID- 24292831
TI  - Arrestin interaction with E3 ubiquitin ligases and deubiquitinases: functional
      and therapeutic implications.
AB  - Arrestins constitute a small family of four homologous adaptor proteins
      (arrestins 1-4), which were originally identified as inhibitors of signal
      transduction elicited by the seven-transmembrane G protein-coupled receptors.
      Currently arrestins (especially arrestin2 and arrestin3; also called beta
      arrestin1 and beta-arrestin2) are known to be activators of cell signaling and
      modulators of endocytic trafficking. Arrestins mediate these effects by binding
      to not only diverse cell-surface receptors but also by associating with a variety
      of critical signaling molecules in different intracellular compartments. Thus,
      the functions of arrestins are multifaceted and demand interactions with a host
      of proteins and require an array of selective conformations. Furthermore,
      receptor ligands that specifically induce signaling via arrestins are being
      discovered and their physiological roles are emerging. Recent evidence suggests
      that the activity of arrestin is regulated in space and time by virtue of its
      dynamic association with specific enzymes of the ubiquitination pathway.
      Ubiquitin-dependent, arrestin-mediated signaling could serve as a potential
      platform for developing novel therapeutic strategies to target transmembrane
      signaling and physiological responses. 

PMID- 24292832
TI  - Self-association of arrestin family members.
AB  - Mammals express four arrestin subtypes, three of which have been shown to self
      associate. Cone photoreceptor-specific arrestin-4 is the only one that is a
      constitutive monomer. Visual arrestin-1 forms tetramers both in crystal and in
      solution, but the shape of its physiologically relevant solution tetramer is very
      different from that in the crystal. The biological role of the self-association
      of arrestin-1, expressed at very high levels in rod and cone photoreceptors,
      appears to be protective, reducing the concentration of cytotoxic monomers. The
      two nonvisual arrestin subtypes are highly homologous, and self-association of
      both is facilitated by IP6, yet they form dramatically different oligomers.
      Arrestin-2 apparently self-associates into "infinite" chains, very similar to
      those observed in IP6-soaked crystals, where IP6 connects the concave sides of
      the N- and C-domains of adjacent protomers. In contrast, arrestin-3 only forms
      dimers, in which IP6 likely connects the C-domains of two arrestin-3 molecules.
      Thus, each of the three self-associating arrestins does it in its own way,
      forming three different types of oligomers. The physiological role of the
      oligomerization of arrestin-1 and both nonvisual arrestins might be quite
      different, and in each case it remains to be definitively elucidated. 

PMID- 24292833
TI  - Arrestin-dependent activation of ERK and Src family kinases.
AB  - The four members of the mammalian arrestin family, two visual and two nonvisual,
      share the property of stimulus-dependent docking to G protein-coupled receptors.
      This conformational selectivity permits them to function in receptor
      desensitization, as arrestin binding sterically inhibits G protein coupling. The
      two nonvisual arrestins further act as adapter proteins, linking receptors to the
      clathrin-dependent endocytic machinery and regulating receptor sequestration,
      intracellular trafficking, recycling, and degradation. Arrestins also function as
      ligand-regulated scaffolds, recruiting catalytically active proteins into
      receptor-based multiprotein "signalsome" complexes. Arrestin binding thus marks
      the transition from a transient G protein-coupled state on the plasma membrane to
      a persistent arrestin-coupled state that continues to signal as the receptor
      internalizes. Two of the earliest discovered and most studied arrestin-dependent
      signaling pathways involve regulation of Src family nonreceptor tyrosine kinases
      and the ERK1/2 mitogen-activated kinase cascade. In each case, arrestin
      scaffolding imposes constraints on kinase activity that dictate signal duration
      and substrate specificity. Evidence suggests that arrestin-bound ERK1/2 and Src
      not only play regulatory roles in receptor desensitization and trafficking but
      also mediate longer term effects on cell growth, migration, proliferation, and
      survival. 

PMID- 24292835
TI  - Arrestin-mediated activation of p38 MAPK: molecular mechanisms and behavioral
      consequences.
AB  - Studies of kappa opioid receptor signaling mechanisms during the last decade have
      demonstrated that agonist activation of the receptor results in Gbetagamma
      dependent signaling and distinct arrestin-dependent signaling events. Gbetagamma
      dependent signaling results in ion channel regulation causing neuronal
      inhibition, inhibition of transmitter release, and subsequent analgesic
      responses. In contrast, arrestin-dependent signaling events result in p38 MAPK
      activation and subsequent dysphoric and proaddictive behavioral responses.
      Resolution of these two branches of signaling cascades has enabled strategies
      designed to identify pathway-selective drugs that may have unique therapeutic
      utilities. 

PMID- 24292834
TI  - Arrestin-dependent activation of JNK family kinases.
AB  - The activity of all mitogen-activated protein kinases (MAPKs) is stimulated via
      phosphorylation by upstream MAPK kinases (MAPKK), which are in their turn
      activated via phosphorylation by MAPKK kinases (MAPKKKs). The cells ensure the
      specificity of signaling in these cascades by employing a variety of scaffolding
      proteins that bind matching MAPKKKs, MAPKKs, and MAPKs. All four vertebrate
      arrestin subtypes bind JNK3, but only arrestin-3 serves as a scaffold, promoting
      JNK3 activation in intact cells. Arrestin-3-mediated JNK3 activation does not
      depend on arrestin-3 interaction with G protein-coupled receptors (GPCRs), as
      demonstrated by the ability of some arrestin mutants that cannot bind receptors
      to activate JNK3, whereas certain mutants with enhanced GPCR binding fail to
      promote JNK3 activation. Recent findings suggest that arrestin-3 directly binds
      both MAPKKs necessary for JNK activation and facilitates JNK3 phosphorylation at
      both Thr (by MKK4) and Tyr (by MKK7). JNK3 is expressed in a limited set of cell
      types, whereas JNK1 and JNK2 isoforms are as ubiquitous as arrestin-3. Recent
      study showed that arrestin-3 facilitates the activation of JNK1 and JNK2,
      scaffolding MKK4/7-JNK1/2/3 signaling complexes. In all cases, arrestin-3 acts by
      bringing the kinases together: JNK phosphorylation shows biphasic dependence on
      arrestin-3, being enhanced at lower and suppressed at supraoptimal
      concentrations. Thus, arrestin-3 regulates the activity of multiple JNK isoforms,
      suggesting that it might play a role in survival and apoptosis of all cell types.

PMID- 24292836
TI  - Arrestin-dependent localization of phosphodiesterases.
AB  - Many G-protein-coupled receptors trigger the synthesis of cAMP in order to
      transduce signals from the membrane into the cell cytoplasm. As stimulation of
      each receptor type results in a specific physiological outcome,
      compartmentalization of proteins that make, break, and are activated by cAMP
      underpin receptor-specific responses. Until 2002, it was thought that static
      compartmentalization of phosphodiesterase 4 (PDE4), conferred by N-terminal
      targeting sequences, was one way to shape intricate cAMP gradients that formed
      after receptor activation. Discovery of the PDE4-beta-arrestin complex
      represented a major breakthrough in cAMP signaling, as it spurred the initial
      realization that PDE4s could be transported to sites of high cAMP to orchestrate
      destruction of the second messenger at the same time as the receptor's signal to
      the G-protein is silenced. This chapter charts the scientific process that led to
      the discovery and characterization of the PDE4-beta-arrestin interaction and
      discusses the known functions of this signaling complex. 

PMID- 24292838
TI  - Molecular mechanisms underlying beta-arrestin-dependent chemotaxis and actin
      cytoskeletal reorganization.
AB  - beta-Arrestins play a crucial role in cell migration downstream of multiple G
      protein-coupled receptors (GPCRs) through multiple mechanisms. There is
      considerable evidence that beta-arrestin-dependent scaffolding of actin assembly
      proteins facilitates the formation of a leading edge in response to a chemotactic
      signal. Conversely, there is substantial support for the hypothesis that beta
      arrestins facilitate receptor turnover through their ability to desensitize and
      internalize GPCRs. This chapter discusses both theories for beta-arrestin
      dependent chemotaxis in the context of recent studies, specifically addressing
      known actin assembly proteins regulated by beta-arrestins, chemokine receptors,
      and signaling by chemotactic receptors. 

PMID- 24292839
TI  - Arrestins in host-pathogen interactions.
AB  - In the context of host-pathogen interaction, host cell receptors and signaling
      pathways are essential for both invading pathogens, which exploit them for their
      own profit, and the defending organism, which activates early mechanism of
      defense, known as innate immunity, to block the aggression. Because of their
      central role as scaffolding proteins downstream of activated receptors, beta
      arrestins are involved in multiple signaling pathways activated in host cells by
      pathogens. Some of these pathways participate in the innate immunity and the
      inflammatory response. Other beta-arrestin-dependent pathways are actually
      hijacked by microbes and toxins to penetrate into host cells and spread in the
      organism.

PMID- 24292840
TI  - Arrestin regulation of small GTPases.
AB  - The regulation of small GTPases by arrestins is a relatively new way by which
      arrestin can exert influence over cell signalling cascades, hence, molecular
      interactions and specific binding partners are still being discovered. A pathway
      showcasing the regulation of GTPase activity by beta-arrestin was first
      elucidated in 2001. Since this original study, growing evidence has emerged for
      arrestin modulation of GTPase activity through direct interactions and also via
      the scaffolding of GTPase regulatory proteins. Given the importance of small
      GTPases in a variety of essential cellular functions, pharmacological
      manipulation of this pathway may represent an area with therapeutic potential,
      particularly with respect to cancer pathology and cardiac hypertrophy.The
      regulation of small GTPases by arrestins is a relatively new way by which
      arrestin can exert influence over cell signalling cascades, hence, molecular
      interactions and specific binding partners are still being discovered. A pathway
      showcasing the regulation of GTPase activity by beta-arrestin was first
      elucidated in 2001. Since this original study, growing evidence has emerged for
      arrestin modulation of GTPase activity through direct interactions and also via
      the scaffolding of GTPase regulatory proteins. Given the importance of small
      GTPases in a variety of essential cellular functions, pharmacological
      manipulation of this pathway may represent an area with therapeutic potential,
      particularly with respect to cancer pathology and cardiac hypertrophy. 

PMID- 24292837
TI  - Arrestins in apoptosis.
AB  - Programmed cell death (apoptosis) is a coordinated set of events eventually
      leading to the massive activation of specialized proteases (caspases) that cleave
      numerous substrates, orchestrating fairly uniform biochemical changes than
      culminate in cellular suicide. Apoptosis can be triggered by a variety of
      stimuli, from external signals or growth factor withdrawal to intracellular
      conditions, such as DNA damage or ER stress. Arrestins regulate many signaling
      cascades involved in life-or-death decisions in the cell, so it is hardly
      surprising that numerous reports document the effects of ubiquitous nonvisual
      arrestins on apoptosis under various conditions. Although these findings hardly
      constitute a coherent picture, with the same arrestin subtypes, sometimes via the
      same signaling pathways, reported to promote or inhibit cell death, this might
      reflect real differences in pro- and antiapoptotic signaling in different cells
      under a variety of conditions. Recent finding suggests that one of the nonvisual
      subtypes, arrestin-2, is specifically cleaved by caspases. Generated fragment
      actively participates in the core mechanism of apoptosis: it assists another
      product of caspase activity, tBID, in releasing cytochrome C from mitochondria.
      This is the point of no return in committing vertebrate cells to death, and the
      aspartate where caspases cleave arrestin-2 is evolutionary conserved in
      vertebrate, but not in invertebrate arrestins. In contrast to wild-type arrestin
      2, its caspase-resistant mutant does not facilitate cell death. 

PMID- 24292841
TI  - GPCRs and arrestins in airways: implications for asthma.
AB  - The obstructive lung disease asthma is treated by drugs that target, either
      directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq
      are the primary mediators of airway smooth muscle (ASM) contraction and increased
      airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (beta2AR) promotes
      pro-relaxant signaling in and relaxation of ASM resulting in greater airway
      patency and reversal of life-threatening bronchoconstriction. In addition, GPCR
      mediated functions in other cell types, including airway epithelium and
      hematopoietic cells, are involved in the control of lung inflammation that causes
      most asthma. The capacity of arrestins to regulate GPCR signaling, via either
      control of GPCR desensitization/resensitization or G protein-independent
      signaling, renders arrestins an intriguing therapeutic target for asthma and
      other obstructive lung diseases. This review will focus on the potential role of
      arrestins in those GPCR-mediated airway cell functions that are dysregulated in
      asthma. 

PMID- 24292842
TI  - Arrestins as regulatory hubs in cancer signalling pathways.
AB  - Non-visual arrestins were initially appreciated for the roles they play in the
      negative regulation of G protein-coupled receptors through the processes of
      desensitisation and endocytosis. The arrestins are also now known as protein
      scaffolding platforms that act downstream of multiple types of receptors,
      ensuring relevant transmission of information for an appropriate cellular
      response. They function as regulatory hubs in several important signalling
      pathways that are often dysregulated in human cancers. Interestingly, several
      recent studies have documented changes in expression and localisation of
      arrestins that occur during cancer progression and that correlate with clinical
      outcome. Here, we discuss these advances and how changes in
      expression/localisation may affect functional outputs of arrestins in cancer
      biology. 

PMID- 24292844
TI  - Enantioselective bacterial hydrolysis of amido esters and diamides derived from
      (+/-)-trans-cyclopropane-1,2-dicarboxylic acid.
AB  - Different optically active amido esters, mixed acid esters, amido acids, and
      diamides derived from trans-cyclopropane-1,2-dicarboxylic acid were prepared from
      the commercially available diethyl (+/-)-trans-cyclopropane-1,2-dicarboxylate.
      The key step was the Rhodococcus rhodochrous IFO 15564 catalyzed hydrolysis of
      the corresponding racemic amide. The amidase present in this microorganism showed
      moderate to high enantioselectivity towards these substrates. In addition a
      simple and efficient Curtius rearrangement of some of the enzymatically prepared
      cyclopropanecarboxylic acids allowed us to obtain optically active beta
      aminocyclopropanecarboxylic acid derivatives with high yields and enantiomeric
      excesses. 

PMID- 24292843
TI  - beta-arrestins: regulatory role and therapeutic potential in opioid and
      cannabinoid receptor-mediated analgesia.
AB  - Pain is a complex disorder with neurochemical and psychological components
      contributing to the severity, the persistence, and the difficulty in adequately
      treating the condition. Opioid and cannabinoids are two classes of analgesics
      that have been used to treat pain for centuries and are arguably the oldest of
      "pharmacological" interventions used by man. Unfortunately, they also produce
      several adverse side effects that can complicate pain management. Opioids and
      cannabinoids act at G protein-coupled receptors (GPCRs), and much of their
      effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor
      (CB1R), respectively. These receptors couple to intracellular second messengers
      and regulatory proteins to impart their biological effects. In this chapter, we
      review the role of the intracellular regulatory proteins, beta-arrestins, in
      modulating MOR and CB1R and how they influence the analgesic and side-effect
      profiles of opioid and cannabinoid drugs in vivo. This review of the literature
      suggests that the development of opioid and cannabinoid agonists that bias MOR
      and CB1R toward G protein signaling cascades and away from beta-arrestin
      interactions may provide a novel mechanism by which to produce analgesia with
      less severe adverse effects. 

PMID- 24292845
TI  - Immunohistochemical analyses point to epidermal origin of human Merkel cells.
AB  - Merkel cells, the neurosecretory cells of skin, are essential for light-touch
      responses and may probably fulfill additional functions. Whether these cells
      derive from an epidermal or a neural lineage has been a matter of dispute for a
      long time. In mice, recent studies have clearly demonstrated an epidermal origin
      of Merkel cells. Given the differences in Merkel cell distribution between human
      and murine skin, it is, however, unclear whether the same holds true for human
      Merkel cells. We therefore attempted to gain insight into the human Merkel cell
      lineage by co-immunodetection of the Merkel cell marker protein cytokeratin 20
      (CK20) with various proteins known to be expressed either in epidermal or in
      neural stem cells of the skin. Neither Sox10 nor Pax3, both established markers
      of the neural crest lineage, exhibited any cell co-labeling with CK20. By
      contrast, beta1 integrin, known to be enriched in epidermal stem cells, was found
      in nearly 70 % of interfollicular epidermal and 25 % of follicular Merkel cells.
      Moreover, LRIG1, also enriched in epidermal stem cells, displayed significant co
      immunolabeling with CK20 as well (approximately 20 % in the interfollicular
      epidermis and 7 % in the hair follicle, respectively). Further epidermal markers
      were detected in sporadic Merkel cells. Cells co-expressing CK20 with epidermal
      markers may represent a transitory state between stem cells and differentiated
      cells. beta1 integrin is probably also synthesized by a large subset of mature
      Merkel cells. Summarizing, our data suggest that human Merkel cells may originate
      from epidermal rather than neural progenitors. 

PMID- 24292847
TI  - Source apportionment of PAHs using Unmix model for Yantai costal surface
      sediments, China.
AB  - 16 Polycyclic aromatic hydrocarbons (PAHs) in 20 surface sediments from Yantai
      offshore area were measured. The total PAHs concentrations varied from 450.0 to
      4,299.0 ng/g, with a mean of 2,492.9 ng/g. The high molecular weight (HMW) PAHs
      were most abundant and the ratio ranged from 54.9 % to 81.6 % in all sampling
      stations, indicating that pyrogenic sources were a predominant contribution to
      PAHs pollution. The source contributions of PAHs were estimated based on the EPA
      Unmix 6.0 receptor model. The data were well simulated due to a high correlation
      coefficient between predicted and measured PAHs concentration (R(2) = 0.99). A
      mixed source of coal combustion and traffic pollution contributed to 38.9 % of
      the measured PAHs, followed by diesel emission (38.8 %) and a mixed source of
      biomass combustion and gasoline engine emissions (22.3 %). The current findings
      further validated that Unmix model could be applied to apportion the sources of
      PAHs in sediments.

PMID- 24292846
TI  - ID2 and ID3 protein expression mirrors granulopoietic maturation and
      discriminates between acute leukemia subtypes.
AB  - The inhibitors of DNA binding (ID) inhibit basic helix-loop-helix transcription
      factors and thereby guide cellular differentiation and proliferation. To
      elucidate the involvement of IDs in hematopoiesis and acute leukemias (AL), we
      analyzed ID2 and ID3 expression in hematopoiesis and leukemic blasts in bone
      marrow biopsies (BMB). BMB of healthy stem cell donors (n = 19) and BMB of
      patients with acute myeloid leukemia (AML) with myelodysplasia-related changes
      (AML-MD; n = 19), de novo AML (n = 20), B-acute lymphoblastic leukemia (B-ALL) (n
      = 23), T-ALL (n = 19), were immunohistochemically stained for ID2 and ID3
      expression. The expression patterns were evaluated and quantified for each
      hematopoietic lineage and each leukemia subtype. In normal BMB, immature
      granulopoiesis showed weak ID2 and strong ID3 expression, which was lost during
      maturation (p < 0.001). Erythropoiesis remained negative for ID2/3 (p < 0.001).
      ID2/3 expression differed between immature granulopoiesis and leukemic blasts (p
      < 0.001). Moreover, differential ID2/3 expression was seen between AL subgroups:
      AML, especially AML-MD, had more ID2- (p < 0.001) and ID3-positive (p < 0.001)
      blasts than ALL. We show a comprehensive in situ picture of ID2/3 expression in
      hematopoiesis and AL. Morphologically, ID2/3 proteins seem to be involved in the
      granulopoietic maturation. Importantly, the distinct ID2/3 expression patterns in
      AL indicate a specific deregulation of ID2/3 in the various types of AL and may
      support subtyping of AL. 

PMID- 24292848
TI  - Effect of flubendiamide, lead and their combined exposure on erythrocytic indices
      in water buffalo calves.
AB  - This study evaluated the effect of flubendiamide, lead and their combined oral
      administration on erythrocytic indices in water buffalo calves. Exposure to
      flubendiamide alone resulted in non-significant decreases in Hemoglobin (Hb),
      packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular volume
      (MCV) and mean corpuscular hemoglobin (MCH). Lead acetate exposure resulted in
      significant declines in Hb, PCV and TEC. Combined exposure to flubendiamide and
      lead resulted in declines in Hb, TEC and PCV, but values did not differ
      significantly from corresponding values in the group treated with lead alone.
      Changes in MCV, MCHC and MCH were inconsistent. Plasma calcium concentration
      declined on day 90 in lead-exposed animals, but increased again on day 30 post
      treatment. Results of the present study indicated that flubendiamide exposure
      results in marginal alterations in erythrocytic indices, but lead exposure caused
      significant declines in Hb, PCV and TEC. No interactive effects were observed for
      flubendiamide and lead on changes in erythrocytic indices. 

PMID- 24292849
TI  - Lower lid retraction in thyroid orbitopathy: lamellar shortening or proptosis?
AB  - To investigate any correlation between lower lid retraction and proptosis and
      also between lower lid retraction and lamellar length, as measured by fornix
      depth, in patients with thyroid eye disease (TED). One hundred and sixty-six eyes
      of 83 patients with TED were enrolled. The inferior fornix depth, Hertel
      exophthalmometry measurement, clinical activity score, and lower lid position
      were the main outcome variables. The correlation between lower lid position
      measurement and Hertel measurements and also between the lower lid position
      measurement and inferior fornix depth were evaluated using ANOVA and Pearson's
      tests. The mean age of subjects in patients with and without lid retraction was
      42.8 +/- 1.5 and 47.7 +/- 1.6 years, respectively (P = 0.4). The inferior fornix
      depth in patients with and without lower lid retraction was 11.8 +/- 1.5 and 11.8
      +/- 1.3 mm, respectively (P = 0.960). Pearson's analysis showed a significant
      correlation between the degree of proptosis and lower lid retraction in TED
      patients (P = 0.01). However, no significant correlation was found between the
      level of lower lid retraction and the fornix depth (P = 0.87). The main cause of
      lower lid retraction in TED is proptosis. The beneficial effect of orbital
      decompression on improvement of lower lid retraction must be considered during a
      stepwise surgical approach in TED patients.

PMID- 24292851
TI  - As we begin a new year with the Journal of Plant Research.

PMID- 24292850
TI  - Screening for celiac disease, by endomysial antibodies, in patients with
      unexplained articular manifestations.
AB  - Celiac disease (CD) is an autoimmune systemic disease characterized by not only
      gastrointestinal but also extraintestinal manifestations. The aim of our study
      was to do a serological screening for CD, by IgA endomysial antibodies (EmA), in
      patients with unexplained articular manifestations. Two hundred and eleven
      patients suffering from arthritis or arthralgia without evident cause were
      studied. EmA were determined by indirect immunofluorescence on human umbilical
      cord. Two thousand and five hundred blood donors served as control group. Out of
      211 patients, 5 had EmA (2.37 %). The frequency of EmA in our patients was
      significantly higher than in the control group (2.37 vs. 0.28 %, p < 0.01). All
      patients with positive EmA were female. EmA were significantly more frequent in
      female patients than in female healthy subjects (3 vs. 0.4 %, p < 0.01). Medical
      records revealed: diarrhea (one patient), short size (one patient), anemia (three
      patients), weight loss (two patients) spontaneous abortion (three patients),
      secondary amenorrhea (one patient), early menopause (one patient) and early baby
      death (one patient). Biochemical analysis showed decreased level of calcium (one
      patient), vitamin D (one patient) and cholesterol (one patient). Unexplained
      liver cytolysis was observed in two patients. Radiological examination showed
      demineralization of two hands in one patient. Bone osteodensitometry done in one
      patient out of five revealed lumbar osteopenia. The articular manifestations of
      the five patients did not respond to corticosteroid treatment. CD must be
      considered among the differential diagnosis in a patient with arthritis or
      arthralgia. 

PMID- 24292852
TI  - Therapeutic targeting of the oncostatin M receptor-beta prevents inflammatory
      heart failure.
AB  - Heart failure (HF) is a common and potentially deadly condition, which frequently
      develops as a consequence of various diseases of the heart. The incidence of
      heart failure continuously increases in aging societies illustrating the need for
      new therapeutic approaches. We recently discovered that continuous activation of
      oncostatin M (OSM), a cytokine of the interleukin-6 family that induces
      dedifferentiation of cardiomyocytes, promotes progression of heart failure in
      dilative cardiomyopathy. To evaluate whether inhibition of OSM signaling
      represents a meaningful therapeutic approach to prevent heart failure we
      attenuated OSM-receptor (Obeta) signaling in a mouse model of inflammatory
      dilative cardiomyopathy. We found that administration of an antibody directed
      against the extracellular domain of Obeta or genetic inactivation of a single
      allele of the Obeta gene reduced cardiomyocyte remodeling and dedifferentiation
      resulting in improved cardiac performance and increased survival. We conclude
      that pharmacological attenuation of long-lasting Obeta signaling is a promising
      strategy to treat different types and stages of HF that go along with
      infiltration by OSM-releasing inflammatory cells.

PMID- 24292853
TI  - Development of novel wound dressing composed of hyaluronic acid and collagen
      sponge containing epidermal growth factor and vitamin C derivative.
AB  - This study was designed to investigate the potential of a wound dressing composed
      of hyaluronic acid (HA) and collagen (Col) spongy sheet containing epidermal
      growth factor (EGF) and vitamin C derivative (VC). High-molecular-weight HA
      aqueous solution, hydrolyzed low-molecular-weight HA aqueous solution and heat
      denatured Col aqueous solution were mixed, followed by freeze-drying to obtain a
      spongy sheet. Cross-linkage between Col molecules was induced by UV irradiation
      of the spongy sheet (C-wound dressing). In a similar manner, three types of
      spongy sheet containing EGF (EGF-wound dressing), containing VC (VC-wound
      dressing) or containing EGF and VC (EGF.VC-wound dressing) were prepared by
      freeze-drying the mixed solution containing the specified components. Cytokine
      production by fibroblasts was assessed in a wound surface model using a
      fibroblast-incorporating Col gel sheet (cultured dermal substitute; CDS). CDS was
      elevated to the air-medium interface, onto which each wound dressing was placed
      and cultured for 7 days. Fibroblasts in CDS covered with EGF-wound dressing
      released 3.6 times more VEGF and 3.0 times more HGF, as compared with the C-wound
      dressing. Fibroblasts in CDS covered with EGF.VC-wound dressing released 4.2
      times more VEGF and 6.0 times more HGF, as compared with the C-wound dressing.
      The efficacy of these wound dressings was evaluated in animal tests using
      diabetic mice. Each wound dressing was applied to a full-thickness skin defect on
      the dorsal area measuring 1.5 * 2.0 cm. After 1 week of application, wound
      conditions were evaluated histologically. The EGF.VC-wound dressing more
      effectively promoted granulation tissue formation associated with angiogenesis,
      as compared with other wound dressings.

PMID- 24292854
TI  - Influence of the washing program on the blood processing performance of a
      continuous autotransfusion device.
AB  - The continuous autotransfusion system has been widely used in surgical
      operations. It is known that if oil is added to blood, and this mixture is then
      processed by an autotransfusion device, the added oil is removed and reinfusion
      of fat is prevented by the device. However, there is no detailed report on the
      influence of the particular washing program selected on the levels of blood
      components including blood fat after continuous autotransfusion using such a
      system. Fresh bovine blood samples were processed by a commercial continuous
      autotransfusion device using the "emergency," "quality," and "high-quality"
      programs, applied in random order. Complete blood count (CBC) and serum chemistry
      were analyzed to determine how the blood processing performance of the device
      changes with the washing program applied. There was no significant difference in
      the CBC results obtained with the three washing programs. Although all of the
      blood lipids in the processed blood were decreased compared to those in the blood
      before processing, the levels of triglyceride, phospholipid, and total
      cholesterol after processing via the emergency program were significantly higher
      than those present after processing via the quality and high-quality programs.
      Although the continuous autotransfusion device provided consistent hematocrit
      quality, the levels of some blood lipid components showed significant differences
      among the washing programs. 

PMID- 24292855
TI  - Comprehensive evaluation of fibrin glue as a local drug-delivery system-efficacy
      and safety of sustained release of vancomycin by fibrin glue against local
      methicillin-resistant Staphylococcus aureus infection.
AB  - Infection of prosthetic grafts, especially with methicillin-resistant
      Staphylococcus aureus (MRSA), often becomes critical. Although topical
      administration of antibiotics has been applied empirically, no comprehensive data
      are available showing long-lasting effects and safety of local antibiotic usage.
      By means of animal experiments we assessed fibrin glue (FG) as a slow-release
      vehicle for vancomycin (VCM) against local MRSA infection. Preliminary in-vitro
      experiments were performed to confirm that the FG-VCM mixture maintained
      viscosity as a sealant and led to slow-release of VCM. We next created a
      subcutaneous pocket in a rodent back and implanted a 1 cm (2) woven graft with 1
      ml FG alone, or with serial concentrations of VCM (0-120 mg/ml. n = 3 for each
      group). MRSA of 1 * 10(7) colony-forming units (CFU) was injected into the pocket
      after wound closure. The graft was explanted 7 days later and was submitted for
      culture ("Culture-graft"). Blood samples were obtained for regular blood work,
      serum VCM concentration measurements, and blood culture ("Culture-blood"). The
      pocket tissue was also submitted for measurement of local VCM concentration.
      There was a remarkable infectious response in the group without vancomycin;
      however, no other groups developed any sign of infection. "Culture-graft"
      resulted in MRSA growth for V0 only. "Culture-blood" was negative in all groups,
      and only minimal serum concentrations of vancomycin were detected. One-dose
      topical administration of VCM via FG was effective against localized MRSA graft
      infection without systemic VCM administration. Topical administration of
      antibiotics may help treat difficult graft infections and reduce systemic use of
      potent antibiotics.

PMID- 24292856
TI  - pH changes the aggregation propensity of amyloid-beta without altering the
      monomer conformation.
AB  - Decoupling conformational changes from aggregation will help us understand
      amyloids better. Here we attach Alzheimer's amyloid-beta(1-40) monomers to silver
      nanoparticles, preventing their aggregation, and study their conformation under
      aggregation-favoring conditions using SERS. Surprisingly, the alpha-helical
      character of the peptide remains unchanged between pH 10.5 and 5.5, while the
      solubility changes >100*. Amyloid aggregation can therefore start without
      significant conformational changes.

PMID- 24292857
TI  - Deep brain stimulation in critical care conditions.
AB  - Some neurological conditions require admission to an intensive care unit (ICU)
      where deep sedation and mechanical ventilation are administered to improve the
      patient's condition. Nevertheless, these treatments are not always helpful in
      disease control. At this stage, deep brain stimulation (DBS) could become a
      viable alternative in the treatment of critical neurological conditions with long
      lasting clinical benefit. The value of deep brain stimulation has been
      investigated in the treatment of patients who had undergone surgical electrode
      implants as an emergency procedure to treat acute life-threatening conditions
      requiring admission to neurological ICU (NICU). A before-and-after perspective
      study was examined of seven patients who were treated with DBS for status
      dystonicus (SD) and post-stroke severe hemiballismus. Bilateral globus pallidus
      internus (GPi) DBS was performed in five SD patients and unilateral ventralis
      oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post
      stroke hemiballismus patients. Bilateral GPi-DBS allowed SD resolution in a time
      lapse varying from 1 week to 3 months. No clear improvements compared to the
      baseline clinical condition were observed. Unilateral Voa/Vop-DBS intervention
      controlled hemiballismus after 10 h, and the patient was discharged in 2 days.
      The other patient was transferred from the NICU to the neurosurgery ward after 13
      days. No surgical complications were observed in any of the above procedures.
      Neurostimulation procedures could represent a valuable choice in critical care
      conditions, when involuntary movements are continuous, life-threatening and
      refractory to intensive care procedures. DBS is feasible, safe and effective in
      selected cases. 

PMID- 24292858
TI  - A chloroplast pump model for the CO2 concentrating mechanism in the diatom
      Phaeodactylum tricornutum.
AB  - Prior analysis of inorganic carbon (Ci) fluxes in the diatom Phaeodactylum
      tricornutum has indicated that transport of Ci into the chloroplast from the
      cytoplasm is the major Ci flux in the cell and the primary driving force for the
      CO2 concentrating mechanism (CCM). This flux drives the accumulation of Ci in the
      chloroplast stroma and generates a CO2 deficit in the cytoplasm, inducing CO2
      influx into the cell. Here, the "chloroplast pump" model of the CCM in P.
      tricornutum is formalized and its consistency with data on CO2 and HCO3 (-)
      uptake rates, carbonic anhydrase (CA) activity, intracellular Ci concentration,
      intracellular pH, and RubisCO characteristics is assessed. The chloroplast pump
      model can account for the major features of the data. Analysis of photosynthetic
      and Ci uptake rates as a function of external Ci concentration shows that the
      model has the most difficulty obtaining sufficiently low cytoplasmic CO2
      concentrations to support observed CO2 uptake rates at low external Ci
      concentrations and achieving high rates of photosynthesis. There are multiple
      ways in which model parameters can be varied, within a plausible range, to match
      measured rates of photosynthesis and CO2 uptake. To increase CO2 uptake rates, CA
      activity can be increased, kinetic characteristics of the putative chloroplast
      pump can be enhanced to increase HCO3 (-) export, or the cytoplasmic pH can be
      raised. To increase the photosynthetic rate, the permeability of the pyrenoid to
      CO2 can be reduced or RubisCO content can be increased. 

PMID- 24292859
TI  - Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in
      vitro and in vivo.
AB  - OBJECTIVE AND DESIGN: High mobility group box 1 (HMGB1) protein acts as a late
      mediator of severe vascular inflammatory conditions. Rutin (RT), an active
      flavonoid compound, is well known to possess potent antiplatelet, antiviral and
      antihypertensive properties. In this study, we investigated the anti-inflammatory
      effects of RT against pro-inflammatory responses in human umbilical vein
      endothelial cells (HUVECs) induced by HMGB1 and the associated signaling
      pathways. METHODS: The anti-inflammatory activities of RT were determined by
      measuring permeability, monocytes adhesion and migration, and activation of pro
      inflammatory proteins in HMGB1-activated HUVECs and mice. RESULTS: We found that
      RT potently inhibited HMGB1 release, down-regulated HMGB1-dependent inflammatory
      responses in human endothelial cells, and inhibited HMGB1-mediated
      hyperpermeability and leukocyte migration in mice. In addition, treatment with RT
      resulted in reduced cecal ligation and puncture-induced release of HMGB1 and
      sepsis-related mortality. Further studies revealed that RT suppressed the
      production of tumor necrosis factor-alpha and interleukin 6 and the activation of
      nuclear factor-kappaB and extracellular regulated kinases 1/2 by HMGB1.
      CONCLUSION: Collectively, these results indicate that RT could be a candidate
      therapeutic agent for treatment of various severe vascular inflammatory diseases
      via inhibition of the HMGB1 signaling pathway.

PMID- 24292860
TI  - Objective measurement of minimal fat in normal skeletal muscles of healthy
      children using T2 relaxation time mapping (T2 maps) and MR spectroscopy.
AB  - BACKGROUND: Various skeletal muscle diseases result in fatty infiltration, making
      it important to develop noninvasive biomarkers to objectively measure muscular
      fat. OBJECTIVE: We compared T2 relaxation time mapping (T2 maps) and magnetic
      resonance spectroscopy (MRS) with physical characteristics previously correlated
      with intramuscular fat to validate T2 maps and MRS as objective measures of
      skeletal muscle fat. MATERIALS AND METHODS: We evaluated gluteus maximus muscles
      in 30 healthy boys (ages 5-19 years) at 3 T with T1-weighted images, T2-W images
      with fat saturation, T2 maps with and without fat saturation, and MR
      spectroscopy. We calculated body surface area (BSA), body mass index (BMI) and
      BMI percentile (BMI %). We performed fat and inflammation grading on T1-W imaging
      and fat-saturated T2-W imaging, respectively. Mean T2 values from T2 maps with
      fat saturation were subtracted from T2 maps without fat saturation to determine
      T2 fat values. We obtained lipid-to-water ratios by MR spectroscopy. Pearson
      correlation was used to assess relationships between BSA, BMI, BMI %, T2 fat
      values, and lipid-to-water ratios for each boy. RESULTS: Twenty-four boys
      completed all exams; 21 showed minimal and 3 showed no fatty infiltration. None
      showed muscle inflammation. There was correlation between BSA, BMI, and BMI %,
      and T2 fat values (P < 0.05), and between BMI and BMI %, and lipid-to-water
      ratios (P < 0.05). There was strong correlation between T2 fat values and lipid
      to-water ratios (P < 0.0001, r = 0.83). CONCLUSION: T2 maps and MR spectroscopy
      correlate with physical characteristics associated with fatty infiltration of
      skeletal muscles, even in microscopic amounts, and validate each other. Both
      techniques might enable detection of minimal pathological fatty infiltration in
      children with skeletal muscle disorders.

PMID- 24292861
TI  - Intracranial haemorrhage: an incidental finding at magnetic resonance imaging in
      a cohort of late preterm and term infants.
AB  - BACKGROUND: Intracranial haemorrhage (ICH) in term newborns has been increasingly
      recognised but the occurrence in late preterm infants and the clinical
      presentation are still unclear. OBJECTIVE: To investigate the appearance of
      intracranial haemorrhage at MRI in a cohort of infants born at 34 weeks'
      gestation or more and to correlate MRI findings with neonatal symptoms. MATERIALS
      AND METHODS: We retrospectively reviewed neonatal brain MRI scans performed
      during a 3-year period. We included neonates >=34 weeks' gestation with
      intracranial haemorrhage and compared findings with those in babies without
      intracranial haemorrhage. Babies were classified into three groups according to
      haemorrhage location: (1) infratentorial, (2) infra- and supratentorial, (3)
      infra- and supratentorial + parenchymal involvement. RESULTS: Intracranial
      haemorrhage was observed in 36/240 babies (15%). All of these 36 had subdural
      haemorrhage. Sixteen babies were included in group 1; 16 in group 2; 4 in group
      3. All infants in groups 1 and 2 were asymptomatic except one who was affected by
      intraventricular haemorrhage grade 3. Among the infants in group 3, who had
      intracranial haemorrhage with parenchymal involvement, three of the four (75%)
      presented with acute neurological symptoms. Uncomplicated spontaneous vaginal
      delivery was reported in 20/36 neonates (56%), vacuum extraction in 4 (11%) and
      caesarean section in 12 (33%). Babies with intracranial haemorrhage had
      significantly higher gestational age (38 +/- 2 weeks vs. 37 +/- 2 weeks) and
      birth weight (3,097 +/- 485 g vs. 2,803 +/- 741 g) compared to babies without
      intracranial haemorrhage and were more likely to be delivered vaginally than by
      caesarian section. CONCLUSION: Mild intracranial haemorrhage (groups 1 and 2) is
      relatively common in late preterm and term infants, although it mostly represents
      an incidental finding in clinically asymptomatic babies; early neurological
      symptoms appear to be related to parenchymal involvement.

PMID- 24292862
TI  - Pediatric Radiology Editorial Board - acknowledgements and updates.

PMID- 24292863
TI  - Synchronized reinjection and coalescence of droplets in microfluidics.
AB  - Coalescence of two kinds of pre-processed droplets is necessary to perform
      chemical and biological assays in droplet-based microfluidics. However, a robust
      technique to accomplish this does not exist. Here we present a microfluidic
      device to synchronize the reinjection of two different kinds of droplets and
      coalesce them, using hydrostatic pressure in conjunction with a conventional
      syringe pump. We use a device consisting of two opposing T-junctions for
      reinjecting two kinds of droplets and control the flows of the droplets by
      applying gravity-driven hydrostatic pressure. The hydrostatic-pressure operation
      facilitates balancing the droplet reinjection rates and allows us to synchronize
      the reinjection. Furthermore, we present a simple but robust module to coalesce
      two droplets that sequentially come into the module, regardless of their arrival
      times. These re-injection and coalescence techniques might be used in lab-on-chip
      applications requiring droplets with controlled numbers of solid materials, which
      can be made by coalescing two pre-processed droplets that are formed and sorted
      in devices. 

PMID- 24292864
TI  - Native Fluorescence and Time Resolved Fluorescence Spectroscopic Characterization
      of Normal and Malignant Oral Tissues Under UV Excitation--an In Vitro Study.
AB  - The present work aims to investigates the native fluorescence and time resolved
      fluorescence spectroscopic characterization of oral tissues under UV excitation.
      The fluorescence emission spectra of oral tissues at 280 nm excitation were
      obtained. From the spectra, it was observed that the alteration in the
      biochemical and morphological changes present in tissues. Subsequently, the Full
      width at Half Maximum (FWHM) of every individual spectra of 20 normal and 40
      malignant subjects were calculated. The student's t-test analysis reveals that
      the data were statistically significant (p = 0.001). The fluorescence excitation
      spectra at 350 nm emission of malignant tissues confirms the alteration in
      protein fluorescence with respect to normal counterpart. To quantify the observed
      spectral differences, the two ratio variables R1 = I275/I310 and R2 = I310/I328
      were introduced in the excitation spectra. Among them, the Linear Discriminant
      Analysis (LDA) of R1 reveals better classification with 86.4 % specificity and
      82.5 % sensitivity. The fluorescence decay kinetics of oral tissues was obtained
      at 350 nm emission and it was found that the decay kinetics was triple
      exponential. Then the ROC analysis of fractional amplitudes and component
      lifetime reveals that the average lifetime shows 77 % sensitivity and 70 %
      specificity with the cut off value 4.85 ns. Briefly, the average lifetime
      exhibits better statistical significance when compared to fractional amplitudes
      and component lifetimes. 

PMID- 24292866
TI  - Thotneosides A, B and C: potent antioxidants from nepalese crude drug, leaves of
      Aconogonon molle.
AB  - Three new glycosides: thotneoside A (quercetin 3-O-(6"-O-phenylacetyl)-beta-D
      galactopyranoside) (1), thotneoside B (quercetin 3-O-(6"-O-phenylacetyl)-beta-D
      glucopyranoside) (2) and thotneoside C (3-methyl-2-butenoic acid 1-O-beta-D
      glucopyranoside) (3), together with nine known compounds; quercetin (4),
      quercetin 3-O-beta-D-galactopyranoside (5), quercetin 3-O-(6"-O-galloyl)-beta-D
      galactopyranoside (6), quercetin 3-O-beta-D-galacturonopyranoside (7), quercetin
      3-O-beta-D-glucuronopyranoside (8), quercetin 3-O-alpha-L-rhamnopyranoside (9),
      rutin (10), quercetin 3-O-alpha-L-arabinopyranoside (11) and 2,4,6
      trihydroxyacetophenone 2-O-beta-D-glucopyranoside (12) have been isolated from
      the shade dried leaves of Aconogonon molle, commonly known as "Thotne" in Nepal.
      The structures were elucidated on the basis of chemical and spectroscopic
      methods. All of these compounds were isolated for the first time from A. molle
      and their in vitro antioxidant activity was evaluated by 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free radical scavenging assay. Quercetin (4) and its
      glycosides (1-2, 5-11) showed potent free radical scavenging activity. 

PMID- 24292868
TI  - Patient preferences regarding intraoperative versus external beam radiotherapy
      following breast-conserving surgery.
AB  - The TARGIT-A Trial is an international randomized, prospective trial comparing
      intraoperative radiotherapy (IORT) for equivalence to external beam radiotherapy
      (EBRT) following lumpectomy for invasive breast cancer in selected low-risk
      patients; early results suggest that outcomes are similar. In addition to
      effectiveness data and cost considerations, the preferences of patients should
      help inform practice. This study was undertaken to explore and quantify
      preference in choosing between IORT and the current standard, EBRT. Eligible
      subjects were current or past candidates for breast-conserving surgery and
      radiation being seen at the University of California, San Francisco Breast Care
      Center. A trade-off technique varying the risk of local recurrence for IORT was
      used to quantify any additional accepted risk that these patients would accept to
      receive either treatment. Patients were first presented with a slideshow
      comparing EBRT with the experimental IORT option before being asked their
      preferences given hypothetical 10-year local recurrence risks. Patients were then
      given a questionnaire on demographic, social and clinical factors. Data from 81
      patients were analyzed. The median additional accepted risk to have IORT was 2.3
      % (-9 to 39 %), mean 3.2 %. Only 7 patients chose to accept additional risk for
      EBRT; 22 accepted IORT at no additional risk; and the remaining 52 chose IORT
      with some additional risk. Patients weigh trade-offs of risks and benefits when
      presented with medical treatment choices. Our results show that the majority of
      breast cancer patients will accept a small increment of local risk for a simpler
      delivery of radiation. Further studies that incorporate outcome and side effect
      data from the TARGIT-A trial clarify the expected consequences of a local
      recurrence, and include an expanded range of radiation options that could help
      guide clinical decision making in this area. 

PMID- 24292867
TI  - Breast cancer susceptibility risk associations and heterogeneity by E-cadherin
      tumor tissue expression.
AB  - E-cadherin is involved in cell-cell adhesion and epithelial-to-mesenchymal
      transitions. In cancers, loss or inactivation of E-cadherin is associated with
      epithelial cell proliferation and invasion. Here, we sought to determine, if risk
      associations for 18 breast cancer susceptibility single nucleotide polymorphisms
      (SNPs) differed by E-cadherin tumor tissue expression in the Polish Breast Cancer
      Study (PBCS), using data on 1,347 invasive breast cancer cases and 2,366
      controls. E-cadherin expression (low/high) was assessed using immunohistochemical
      staining of tumor tissue microarrays. Replication data on 2,006 cases and 6,714
      controls from the Study of Epidemiology and Risk Factors in Cancer Heredity was
      used to follow-up promising findings from PBCS. In PBCS, we found the rs11249433
      SNP at the 1p11.2 locus to be more strongly associated with risk of E-cadherin
      low tumors (OR = 1.30, 95 % CI = 1.08-1.56) than with E-cadherin high tumors [OR
      = 1.06, 95 % CI = 0.95-1.18; case-only p-heterogeneity (p-het) = 0.05]. Findings
      in PBCS for rs11249433 were replicated in SEARCH. Combined analyses of the two
      datasets for SNP rs11249433 revealed significant heterogeneity by E-cadherin
      expression (combined case-only p-het = 0.004). Further, among carriers of
      rs11249433, the highest risk was seen for E-cadherin low tumors that were ER
      positive and of lobular histology. Our results in two independent data sets
      suggest that rs11249433, which is located between the NOTCH2 and FCGR1B genes
      within the 1p11.2 locus, is more strongly associated with risk of breast tumors
      with low or absent E-cadherin expression, and suggest that evaluation of E
      cadherin tumor tissue expression may be useful in clarifying breast cancer risk
      factor associations. 

PMID- 24292865
TI  - The emerging role of genomics in the diagnosis and workup of congenital urinary
      tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1.
AB  - BACKGROUND: Copy number variants (CNVs) are increasingly recognized as an
      important cause of congenital malformations and likely explain over 16% of cases
      of congenital anomalies of the kidney and urinary tract (CAKUT). Here, we
      illustrate how a molecular diagnosis of CNV can be beneficial to the clinical
      management of a pediatric patient presenting with CAKUT and other organ defects.
      METHODS: We describe a 14-year-old girl with a large de novo deletion of
      chromosome 3q13.31-22.1 that disrupts 101 known genes. The patient presented with
      CAKUT, neurodevelopmental delay, agenesis of corpus callosum (ACC), cardiac
      malformations, electrolyte and endocrine disorders, skeletal abnormalities and
      dysmorphic features. We performed extensive annotation of the deleted region to
      prioritize genes for specific phenotypes and to predict future disease risk.
      RESULTS: Our case defined new minimal chromosomal candidate regions for both
      CAKUT and ACC. The presence of the CASR gene in the deleted interval predicted a
      diagnosis of hypocalciuric hypercalcemia, which was confirmed by the serum and
      urine chemistries. Our gene annotation explained clinical hypothyroidism and
      predicted that the index case is at increased risk of thoracic aortic aneurysm,
      renal cell carcinoma and myeloproliferative disorder. CONCLUSIONS: Extended
      annotation of CNV regions refines the diagnosis and uncovers previously
      unrecognized phenotypic features. This approach enables personalized treatment
      and prevention strategies in patients harboring genomic deletions.

PMID- 24292869
TI  - Possible role of the aromatase-independent steroid metabolism pathways in hormone
      responsive primary breast cancers.
AB  - Aromatase inhibitors (AIs) exert antiproliferative effects by reducing local
      estrogen production from androgens in postmenopausal women with hormone
      responsive breast cancer. Previous reports have shown that androgen metabolites
      generated by the aromatase-independent enzymes, 5alpha-androstane-3beta, 17beta
      diol (3beta-diol), androst-5-ene-3beta, and 17beta-diol (A-diol), also activate
      estrogen receptor (ER) alpha. Estradiol (E2) can also reportedly be generated
      from estrone sulfate (E1S) pooled in the plasma. Estrogenic steroid-producing
      aromatase-independent pathways have thus been proposed as a mechanism of AI
      resistance. However, it is unclear whether these pathways are functional in
      clinical breast cancer. To investigate this issue, we assessed the
      transcriptional activities of ER in 45 ER-positive human breast cancers using the
      adenovirus estrogen-response element-green fluorescent protein assay and mRNA
      expression levels of the ER target gene, progesterone receptor, as indicators of
      ex vivo and in vivo ER activity, respectively. We also determined mRNA expression
      levels of 5alpha-reductase type 1 (SRD5A1) and 3beta-hydroxysteroid dehydrogenase
      type 1 (3beta-HSD type 1; HSD3B1), which produce 3beta-diol from androgens, and
      of steroid sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type 1 (17beta
      HSD type 1; HSD17B1), which produce E2 or A-diol from E1S or
      dehydroepiandrosterone sulfate. SRD5A1 and HSD3B1 expression levels were
      positively correlated with ex vivo and in vivo ER activities. STS and HSD17B1
      expression levels were positively correlated with in vivo ER activity alone.
      Elevated expression levels of these steroid-metabolizing enzymes in association
      with high in vivo ER activity were particularly notable in postmenopausal
      patients. Analysis of the expression levels of steroid-metabolizing enzymes
      revealed positive correlations between SRD5A1 and HSD3B1, and STS and HSD17B1.
      These findings suggest that the SRD5A1-HSD3B1 as well as the STS-HSD17B pathways,
      could contributes to ER activation, especially postmenopause. These pathways
      might function as an alternative estrogenic steroid-producing, aromatase
      independent pathways. 

PMID- 24292870
TI  - Dual-colour CISH is a reliable alternative to FISH for assessment of
      topoisomerase 2-alpha amplification in breast carcinomas.
AB  - Anthracyclines are among the most powerful antineoplastic drugs available for
      breast cancer treatment. Although HER2 amplification has been postulated to
      predict anthracycline benefit, numerous reports have demonstrated that HER2/TOP2A
      co-amplification is the clinically useful predictive marker of response to
      anthracyclines. The standard technique to evaluate gene status for target therapy
      selection is fluorescence in situ hybridization (FISH), but this technique has
      some disadvantages. Dual-colour chromogenic in situ hybridization (CISH) is an
      extension of the FISH protocol that allows bright-field microscopy and thus
      represents a user-friendly alternative to FISH. In order to evaluate whether dual
      colour CISH is a reliable alternative to FISH in determining TOP2A gene
      amplification and to determine the frequency with which TOP2A and HER2 were co
      amplified, we analysed 100 invasive breast cancer specimens (70 consecutive and
      30 HER2-amplified samples) using tissue microarrays. Thus, a 99 % agreement was
      found between TOP2A status determined by dual-colour CISH and FISH, as well as a
      high degree of correlation in TOP2A ratios using both techniques. TOP2A gene
      amplification was present in 8.6 % of the 70 consecutive samples studied, all of
      which were HER2-amplified. Co-amplification of TOP2A was observed in 46.5 % of
      the additional 30 HER2-amplified samples (no TOP2A amplification was seen in non
      amplified HER2 samples). We conclude that dual-colour CISH represents an
      excellent alternative to FISH for determination of TOP2A gene status in invasive
      breast cancer. Our results showing TOP2A amplification only in HER2-amplified
      cases also add to the evidence that TOP2A determination should be restricted to
      those cases. 

PMID- 24292871
TI  - Polycyclic aromatic hydrocarbon concentrations, mutagenicity, and Microtox(r)
      acute toxicity testing of Peruvian crude oil and oil-contaminated water and
      sediment.
AB  - The oil industry is a major source of contamination in Peru, and wastewater and
      sediments containing oil include harmful substances that may have acute and
      chronic effects. This study determined polycyclic aromatic hydrocarbon (PAH)
      concentrations by GC/MS, mutagenicity using TA98 and TA100 bacterial strains with
      and without metabolic activation in the Muta-ChromoPlateTM test, and Microtox(r)
      5-min EC50 values of Peruvian crude oil, and water and sediment pore water from
      the vicinity of San Jose de Saramuro on the Maranon River and Villa Trompeteros
      on the Corrientes River in Loreto, Peru. The highest total PAH concentration in
      both areas was found in water (Saramuro = 210.15 MUg/ml, Trompeteros = 204.66
      MUg/ml). Total PAH concentrations in water from San Jose de Saramuro ranged from
      9.90 to 210.15 MUg/ml (mean = 66.48 MUg/ml), while sediment pore water
      concentrations ranged from 2.19 to 70.41 MUg/ml (mean = 24.33 MUg/ml). All water
      samples tested from Saramuro and Trompeteros sites, and one out of four sediment
      pore water samples from Trompeteros, were found to be mutagenic (P < 0.001). One
      sediment pore water sample in Saramuro was determined to have a measurable
      toxicity (Microtox EC50 = 335.1 mg/l), and in Trompeteros, the EC50 in water and
      sediment pore water ranged from 25.67 to 133.86 mg/l. Peruvian crude oil was
      mutagenic using the TA98 strain with metabolic activation, and the EC50 was 17.18
      mg/l. The two areas sampled had very high PAH concentrations that were most
      likely associated with oil activities, but did not lead to acute toxic effects.
      However, since most of the samples were mutagenic, it is thought that there is a
      greater potential for chronic effects.

PMID- 24292872
TI  - Spatial heterogeneity of stream environmental conditions and macroinvertebrates
      community in an agriculture dominated watershed and management implications for a
      large river (the Liao River, China) basin.
AB  - Understanding the effects of watershed land uses (e.g., agriculture, urban
      industry) on stream ecological conditions is important for the management of
      large river basins. A total of 41 and 56 stream sites (from first to fourth
      order) that were under a gradient of watershed land uses were monitored in 2009
      and 2010, respectively, in the Liao River Basin, Northeast China. The monitoring
      results showed that a total of 192 taxa belonging to four phyla, seven classes,
      21 orders and 91 families were identified. The composition of macroinvertebrate
      community in the Liao River Basin was dominated by aquatic insect taxa
      (Ephemeroptera and Diptera), Oligochaeta and Molluscs. The functional feeding
      group GC (Gatherer/Collector) was dominant in the whole basin. Statistical
      results showed that sites with less watershed impacts (lower order sites) were
      characterized by higher current velocity and habitat score, more sensitive taxa
      (e.g., Ephemeroptera), and the substrate was dominated by high percentage of
      cobble and pebble. The sites with more impacts from agriculture and urban
      industry (higher order sites) were characterized by higher biochemical (BOD5) and
      chemical oxygen demand (COD), more tolerant taxa (e.g., Chironominae), and the
      substrate was dominated by silt and sand. Agriculture and urban-industry
      activities have reduced habitat condition, increased organic pollutants, reduced
      macroinvertebrate abundance, diversity, and sensitive taxa in streams of the
      lower Liao River Basin. Restoration of degraded habitat condition and control of
      watershed organic pollutants could be potential management priorities for the
      Basin. 

PMID- 24292873
TI  - Early postoperative prophylactic noninvasive ventilation after major lung
      resection in COPD patients: a randomized controlled trial.
AB  - OBJECTIVES: To investigate whether prophylactic postoperative NIV prevents
      respiratory complications following lung resection surgery in COPD patients.
      METHODS: In seven thoracic surgery departments, 360 COPD patients undergoing lung
      resection surgery were randomly assigned to two groups: conventional
      postoperative treatment without (n = 179) or with (n = 181) prophylactic NIV,
      applied intermittently during 6 h per day for 48 h following surgery. The primary
      endpoint was the rate of acute respiratory events (ARE) at 30 days
      postoperatively (ITT analysis). Secondary endpoints were acute respiratory
      failure (ARF), intubation rate, mortality rate, infectious and non-infectious
      complications, and duration of ICU and hospital stay. MEASUREMENTS AND MAIN
      RESULTS: ARE rates did not differ between the prophylactic NIV and control groups
      (57/181, 31.5 vs. 55/179, 30.7%, p = 0.93). ARF rate was 18.8% in the
      prophylactic NIV group and 24.5% in controls (p = 0.20). Re-intubation rates were
      similar in the prophylactic NIV and control group [10/181 (5.5%) and 13/179
      (7.2%), respectively, p = 0.53]. Mortality rates were 5 and 2.2% in the control
      and prophylactic NIV groups, respectively (p = 0.16). Infectious and non
      infectious complication rates, and duration of ICU and hospital stays were
      similar between groups. CONCLUSIONS: Prophylactic postoperative NIV did not
      reduce the rate of ARE in COPD patients undergoing lung resection surgery and did
      not influence other postoperative complications rates, mortality rates, and
      duration of ICU and hospital stay.

PMID- 24292874
TI  - Surprising physiologic side effects of an alternating pressure air mattress
      during prone position in an ARDS patient.

PMID- 24292875
TI  - Sepsis without borders.

PMID- 24292876
TI  - Asbestos exposure among construction workers during demolition of old houses in
      Tehran, Iran.
AB  - Air quality in demolition practices has seldom been evaluated in Iran.
      Accordingly, we evaluated asbestos exposure among Tehran construction workers
      during the demolition of old houses. To identify possible sources of asbestos
      exposure, including thermal insulations, chimney pipes and cement sheets, were
      all sampled. This study also were taken the personal air samples to evaluate any
      asbestos exposure during the demolition. The asbestos fibers found in the samples
      were analyzed by phase-contrast optical microscopy (PCM), scanning electron
      microscopy (SEM) equipped with an energy dispersive X-ray analysis, and polarized
      light microscopy (PLM) methods. Personal monitoring of asbestos fiber levels
      indicated a range from 0.01 to 0.15 PCM f/ml (0.02-0.42 SEM f/ml). The geometric
      mean concentrations were 0.07 PCM f/ml (0.20 SEM f/ml), which is considerably
      higher than the threshold limit value (TLV) proposed by American Conference of
      Governmental Industrial Hygienist (ACGIH), which is 0.1 f/ml. The analysis showed
      a presence in the bulk samples only chrysotile asbestos and an absence of the
      other type asbestos. Therefore, it might be expected that workers who worked in
      the demolition of old houses will suffer from negative effects of exposing to the
      asbestos fibers. 

PMID- 24292877
TI  - Do I just look stressed or am I stressed? Work-related stress in a sample of
      Italian employees.
AB  - Work-related stress is becoming a significant problem in Italy and it is
      therefore essential to advance the theory and methodology required to detect this
      phenomenon at work. Thus, the aim of this paper is to propose a new method for
      evaluating stress at work by measuring the discrepancies between employees'
      perceptions of stress and their leaders' evaluation of the stress of their
      subordinates. In addition, a positive impression scale was added to determine
      whether workers might give socially desirable responses in organizational
      diagnosis. Over 1,100 employees and 200 leaders within several Italian
      organizations were involved in this study. Structural equation modeling was used
      to test such new method for evaluating stress in a model of stress at work that
      incorporates relationships among individual (positive impression), interpersonal
      (workplace bullying) and organizational factors (working conditions, welfare
      culture, training). Results showed that the leaders' capacity to understand
      subordinates' stress is associated with subordinates' psychological well-being
      since higher disagreement between self and leaders' ratings was related to lower
      well-being. We discuss the implications of healthy leadership for the development
      of healthy organizations. 

PMID- 24292878
TI  - The prevalence of musculoskeletal disorder and association with productivity
      loss: a preliminary study among labour intensive manual harvesting activities in
      oil palm plantation.
AB  - Production agriculture such as harvesting in oil palm plantation has been
      frequently associated with MSD and significant loss of productivities. This study
      tends to evaluate from the viewpoint of health, the association between self
      reported prevalence of musculoskeletal disorders and productivities; the impact
      of musculoskeletal disorders on productivity. A cross-sectional study was
      conducted among 143 harvesters in oil palm plantation. A general questionnaire
      was used to collect socio-demographic background data while Nordic
      Musculoskeletal Questionnaire was used to determine the prevalence of MSD.
      Expressed in 4 different indicators; daily harvesting quantity, efficiency score,
      sick leave and presenteeism, the productivity data were analysed for association.
      There is significant association between reported acute prevalence of MSD (within
      7 d) and productivity loss in terms of presenteeism (chi(2)=5.088; p<0.05) as
      well as quantity of daily harvest (chi(2)=7.406; p<0.01). Logistic regression
      adjusted for age, BMI and smoking indicate that harvesters with MSD (past seven
      days) were more likely to be engaged in presenteeism (OR=2.87 95% CI=1.34, 6.14)
      and had lower daily productivity (OR=2.09 95% CI=1.02, 4.29) compared to
      harvesters without MSD (past 7 d). This study reveals that oil palm harvesters
      suffering acute MSD (for the past week) were likely to be still present to work
      and produce half lesser than their healthy counterparts. Thus, further study with
      comprehensive surveillance strategy is essential in order to determine the
      urgency or need of appropriate intervention. 

PMID- 24292879
TI  - Effects of two 15-min naps on the subjective sleepiness, fatigue and heart rate
      variability of night shift nurses.
AB  - The purpose of this study was to examine the effects of two 15-min naps on nurses
      who work at night in a three-shift system. Of the 15 nurses who were included as
      study subjects on a night shift, eight took two short naps (the Nap condition),
      and seven worked without taking a nap (the No-nap condition) during the night
      shift. We measured sublingual temperature and the bispectral index (BIS),
      obtained heart rate and heart rate variability measures from an electrocardiogram
      (ECG), and evaluated sleepiness and fatigue levels every hour using the Visual
      Analog Scale (VAS). Both subjective sleepiness and fatigue increased between 4:00
      and 5:00, with no significant differences observed between the two groups.
      However, the low- to high-frequency ratio (LF/HF) in the Nap condition group was
      found to be significantly lower than in the No-nap condition group. Furthermore,
      a sudden, brief increase in HF values was observed in the No-nap condition group
      in the morning. The results of this study suggest that taking two short naps may
      effectively reduce tension and prevent a brief increase in HF values by
      suppressing sympathetic nervous activity in the morning. 

PMID- 24292880
TI  - Sleep polysomnography and reported stress across 6 weeks.
AB  - Despite the common notion that stress impairs sleep there is little published
      data showing that sleep (polysomnography (PSG)) is impaired across several sleep
      episodes in individuals who complain of daily stress during the same period. The
      present paper aimed at investigating such a connection. 33 subjects had 3 sleeps
      recorded with PSG at home across 6 weeks and kept a sleep/wake diary each day,
      including 3-hourly ratings of stress (scale 1-9). The stress ratings and the
      conventional PSG parameters were averaged across time. A stepwise multiple
      regression analysis showed that the best predictors of stress were Stage 1 sleep
      (beta = 0.49), latency to Stage 1 sleep (0.47) (adjusted for anxiety and age).
      Other sleep continuity variables had significant correlations with stress
      (reversed) but did not enter the multiple regression analysis. The correlation
      between stress before the start of the study and PSG data was not significant. It
      was concluded that moderately increased stress over a longer period of time is
      related to moderate signs of disturbed sleep during that period. This may be of
      importance when considering stress as a work environment problem. 

PMID- 24292881
TI  - MiRNA regulation of TRAIL expression exerts selective cytotoxicity to prostate
      carcinoma cells.
AB  - Prostate carcinoma is the most common cancer for men and among the leading cancer
      related causes. Many evidences have shown that tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) potently induces apoptosis in cancer cells, and
      thus, is a promising biologic agent for prostate carcinoma therapy. However,
      TRAIL expression mediated by the current vectors lacks tumor specificity, thereby
      exerting cytotoxicity to normal cells. To solve this problem, we inserted miRNA
      response elements (MREs), miR-143 and miR-145, expression levels of which were
      reduced in prostate carcinoma, as well as that of miR-122, which is specifically
      expressed in hepatic cells, into adenoviral vectors to control TRAIL expression
      (Ad-TRAIL-M3). qPCR data confirmed that miR-143, miR-145, and miR-122 levels were
      all decreased in prostate carcinoma cell lines and prostate cancer samples from
      patients. Luciferase assays showed that MREs-regulated luciferase expression was
      potently suppressed in normal cells, but not in prostate cancer cells. Ad-TRAIL
      M3, which expresses TRAIL in a MREs-regulated manner, produced high level of
      TRAIL and suppressed the survival of prostate cancer cells by inducing apoptosis,
      while Ad-TRAIL-M3 had no TRAIL expression in normal cells and thus exerted no
      cytotoxicity to them. The studies on PC-3 tumor xenograft in mice further
      confirmed that Ad-TRAIL-M3 was able to inhibit the growth of tumors and possessed
      high biosafety. In conclusion, we successfully generated an adenoviral vector
      that expresses TRAIL in miRNA-regulated mechanism. This miRNA-based gene therapy
      may be promising for prostate carcinoma treatment. 

PMID- 24292882
TI  - Leptin signaling in skeletal muscle after bed rest in healthy humans.
AB  - PURPOSE: This study aimed at determining the effects of bed rest on the skeletal
      muscle leptin signaling system. METHODS: Deltoid and vastus lateralis muscle
      biopsies and blood samples were obtained from 12 healthy young men (mean +/- SD,
      BMI 22.8 +/- 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor
      isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine
      phosphatase 1B (PTP1B) protein expression and signal transducer and activator of
      transcription 3 (STAT3) phosphorylation were analyzed by Western blot. RESULTS:
      After bed rest basal insulin concentration was increased by 53% (P < 0.05), the
      homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin
      concentration by 35% (P < 0.05) with no changes in body fat mass. Although the
      soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar
      excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05).
      OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained
      unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid.
      PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05).
      There was a linear relationship between the increase in vastus lateralis PTP1B
      and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and
      HOMA (r = 0.68, P < 0.05) with bed rest. CONCLUSIONS: One week of bed rest is
      associated with increased leptin levels without augmenting STAT3 phosphorylation
      indicating some degree of leptin resistance in skeletal muscle, which can be
      explained, at least in part, by an elevation of PTP1B protein content in the
      vastus lateralis muscle.

PMID- 24292883
TI  - Evaluation of diabetic retinopathy screening using a non-mydriatic retinal
      digital camera in primary care settings in south Israel.
AB  - To evaluate the effectiveness of the non-mydriatic digital camera for diabetic
      retinopathy (DR) screening. Secondary purposes of the study were to characterize
      diabetic patients being screened for the presence of DR and to calculate the
      sensitivity, specificity, and positive predictive value of the test. All 6,962
      consecutive patients with type 2 diabetes undergoing non-mydriatic digital
      retinal photography between January 1, 2009 and June 30, 2010 in eight community
      health clinics in the south of the country were included. Comparison of a random
      sample of patients who underwent non-mydriatic retinal photography, and who were
      also examined by an ophthalmologist with pupil dilation was also performed. The
      average age of all patients was 64.2 years. A total of 5,960 cases (85.6 % of all
      photographs) were of adequate quality for the diagnosis. DR of any degree was
      found in 1,092 (18.3 %) patients. Normal fundus pictures were found in 49.4 % of
      patients. In 32.2 % of cases, non-DR pathologies were found. Among cases in which
      DR was found, 73.3 % (801 cases) had mild non-proliferative retinopathy (NPDR),
      7.1 % (77 cases) had moderate NPDR, 6.8 % (74 cases) had proliferative
      retinopathy, and 12.8 % (140 cases) had diabetic macular edema. Older patients
      had more chance of having poor quality pictures (p < 0.001 between patients older
      and younger than 70 years). When non-mydriatic fundus photography was compared
      with dilated fundus examination by an ophthalmologist, sensitivity of 99.3 %,
      specificity of 88.3 %, and positive predictive value of 85.3 % were found. Non
      mydriatic digital retinal photography is an efficient method for DR screening.
      The test has high sensitivity and specificity. The test, as performed in
      community health centers in the south of the country, contributed to the early
      diagnosis of >1,000 cases of DR. Many patients can be followed up in a fast and
      efficient way, although the test cannot replace a complete eye examination after
      pupil dilation mainly in older people. Other non-DR sight-threatening ocular
      pathologies can be also detected.

PMID- 24292884
TI  - Trb3 regulates LR axis formation in zebrafish embryos.
AB  - Tribless family proteins are pseudokinases that lack DFG (Asp-Phe-Gly) motif in
      the functional kinase domain, regulating Akt and BMP pathways, insulin
      metabolism, hypoxia, and ubiquitination. This report concerns expression patterns
      and functional roles of trb3 in zebrafish embryonic development. trb3 is
      evolutionarily well-conserved and located on zebrafish chromosome 11.
      Spatiotemporal expression studies show that trb3 transcripts are abundant
      throughout embryogenesis, but confined to mesendodermal cells during the late
      blastula phase. Over-expression of trb3 ventralizes the embryos while a knockdown
      of trb3 using morpholino alters positioning of the heart, liver, and pancreatic
      buds as well as gut looping. Furthermore, constitutive activation of TGF
      signaling with TARAM-A* (TGF-related type I receptor) significantly increases the
      level of trb3 transcripts during the late blastula phase. Over-expression of trb3
      reduces the level of smurf1 transcripts, a member of TGF-signaling. We thus
      propose that Trb3 governs left-right (LR) axis patterning as a component of TGF
      signaling in vertebrate embryonic development. 

PMID- 24292885
TI  - Urimem, a membrane that can store urinary proteins simply and economically, makes
      the large-scale storage of clinical samples possible.
AB  - By nature, biomarker is the measurable change associated with a physiological or
      pathophysiological process. Unlike blood which has mechanisms to minimize changes
      and to keep the internal environment homeostatic, urine is more likely to reflect
      changes of the body and is a better biomarker source. Because of its potential in
      biomarker discovery, urinary proteins should be preserved comprehensively as the
      duration of the patients' corresponding medical records. Here, we propose a
      method to adsorb urinary proteins onto a membrane we named Urimem. This simple
      and inexpensive method requires minimal sample handling, uses no organic
      solvents, and is environmentally friendly. Urine samples were filtered through
      the membrane, and urinary proteins were adsorbed onto the membrane. The proteins
      on the membrane were dried and stored in a vacuum bag, which keeps the protein
      pattern faithfully preserved. The membrane may even permit storage at room
      temperature for weeks. Using this simple and inexpensive method, it is possible
      to begin preserving urine samples from all consenting people. Thus, medical
      research especially biomarker research can be conducted more economically. Even
      more objective large-scale prospective studies will be possible. This method has
      the potential to change the landscape of medical research and medical practice. 

PMID- 24292886
TI  - Quantitative assessment of intragenic receptor tyrosine kinase deletions in
      primary glioblastomas: their prevalence and molecular correlates.
AB  - Intragenic deletion is the most common form of activating mutation among receptor
      tyrosine kinases (RTK) in glioblastoma. However, these events are not detected by
      conventional DNA sequencing methods commonly utilized for tumor genotyping. To
      comprehensively assess the frequency, distribution, and expression levels of
      common RTK deletion mutants in glioblastoma, we analyzed RNA from a set of 192
      glioblastoma samples from The Cancer Genome Atlas for the expression of EGFRvIII,
      EGFRvII, EGFRvV (carboxyl-terminal deletion), and PDGFRADelta8,9. These mutations
      were detected in 24, 1.6, 4.7, and 1.6 % of cases, respectively. Overall, 29 %
      (55/189) of glioblastomas expressed at least one RTK intragenic deletion
      transcript in this panel. For EGFRvIII, samples were analyzed by both
      quantitative real-time PCR (QRT-PCR) and single mRNA molecule counting on the
      Nanostring nCounter platform. Nanostring proved to be highly sensitive, specific,
      and linear, with sensitivity comparable or exceeding that of RNA seq. We
      evaluated the prognostic significance and molecular correlates of RTK
      rearrangements. EGFRvIII was only detectable in tumors with focal amplification
      of the gene. Moreover, we found that EGFRvIII expression was not prognostic of
      poor outcome and that neither recurrent copy number alterations nor global
      changes in gene expression differentiate EGFRvIII-positive tumors from tumors
      with amplification of wild-type EGFR. The wide range of expression of mutant
      alleles and co-expression of multiple EGFR variants suggests that quantitative
      RNA-based clinical assays will be important for assessing the relative expression
      of intragenic deletions as therapeutic targets and/or candidate biomarkers. To
      this end, we demonstrate the performance of the Nanostring assay in RNA derived
      from routinely collected formalin-fixed paraffin-embedded tissue.

PMID- 24292887
TI  - Neuropathology of substance use disorders.
AB  - Addictions to licit and illicit drugs are chronic relapsing brain disorders that
      affect circuits that regulate reward, motivation, memory, and decision-making.
      Drug-induced pathological changes in these brain regions are associated with
      characteristic enduring behaviors that continue despite adverse biopsychosocial
      consequences. Repeated exposure to these substances leads to egocentric behaviors
      that focus on obtaining the drug by any means and on taking the drug under
      adverse psychosocial and medical conditions. Addiction also includes craving for
      the substances and, in some cases, involvement in risky behaviors that can cause
      death. These patterns of behaviors are associated with specific cognitive
      disturbances and neuroimaging evidence for brain dysfunctions in a diverse
      population of drug addicts. Postmortem studies have also revealed significant
      biochemical and/or structural abnormalities in some addicted individuals. The
      present review provides a summary of the evidence that has accumulated over the
      past few years to implicate brain dysfunctions in the varied manifestations of
      drug addiction. We thus review data on cerebrovascular alterations, brain
      structural abnormalities, and postmortem studies of patients who abuse cannabis,
      cocaine, amphetamines, heroin, and "bath salts". We also discuss potential
      molecular, biochemical, and cellular bases for the varied clinical presentations
      of these patients. Elucidation of the biological bases of addiction will help to
      develop better therapeutic approaches to these patient populations. 

PMID- 24292888
TI  - Incremental value of 3-D transesophageal echocardiographic imaging of the mitral
      valve.
AB  - Transesophageal echocardiography provides excellent visualization of the
      posteriorly located mitral valve. Over the last decade, 3-dimensional
      transesophageal echocardiography (3D TEE) has emerged as an exciting imaging
      modality, particularly of the mitral valve. The current generation matrix array
      technology allows the operator to perform 2D and 3D imaging with a single
      transducer. 3D TEE affords the unique ability to view the mitral valve and its
      surrounding structures "en face" in real time (RT), and provide contextual
      anatomical guidance during surgical and transcatheter interventions.
      Additionally, offline quantification has made significant contributions to our
      mechanistic understanding of the normal and diseased mitral valve, and
      alterations induced by therapeutic intervention such as surgical repair. This
      review will address recent advances in the incremental role of 3D TEE in mitral
      valve imaging. 

PMID- 24292889
TI  - Ube3a, the E3 ubiquitin ligase causing Angelman syndrome and linked to autism,
      regulates protein homeostasis through the proteasomal shuttle Rpn10.
AB  - Ubiquitination, the covalent attachment of ubiquitin to a target protein,
      regulates most cellular processes and is involved in several neurological
      disorders. In particular, Angelman syndrome and one of the most common genomic
      forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a
      ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during
      brain development. We have now devised a protocol to screen for substrates of
      this particular ubiquitin ligase. In a neuronal cell system, we find direct
      ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and
      CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is
      targeted for degradation upon ubiquitination by Ube3a, indicating that
      degradation might not be the only effect of Ube3a on its substrates. Furthermore,
      we report the genetic interaction in vivo between Ube3a and the C-terminal part
      of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of
      ubiquitinated proteins, further supporting the biochemical evidence of
      interaction obtained in neuronal cells.

PMID- 24292890
TI  - Investigating the potential causal relationship between parental knowledge and
      youth risky behavior: a propensity score analysis.
AB  - This longitudinal study aims to explore the potential causal relationship between
      parental knowledge and youth risky behavior among a sample of rural, early
      adolescents (84 % White, 47 % male). Using inverse propensity weighting, the
      sample was adjusted by controlling for 33 potential confounding variables.
      Confounding variables include other aspects of the parent-child relationship,
      parental monitoring, demographic variables, and earlier levels of problem
      behavior. The effect of parental knowledge was significant for youth substance
      and polysubstance use initiation, alcohol and cigarette use, attitudes towards
      substance use, and delinquency. Our results suggest that parental knowledge may
      be causally related to substance use during middle school, as the relationship
      between knowledge and youth outcomes remained after controlling for 33 different
      confounding variables. The discussion focuses on understanding issues of
      causality in parenting and intervention implications.

PMID- 24292891
TI  - Elevated resting heart rate and reduced orthostatic tolerance in obese humans.
AB  - BACKGROUND: Obesity is linked with numerous physiological impairments; however,
      its impact on orthostatic tolerance (OT) remains unknown. This study tested the
      hypothesis that OT is reduced in obese individuals, and that reduced heart rate
      (HR) reserve and impaired cerebral autoregulation contribute to impaired OT.
      METHODS: Eleven obese (8 females) and 22 non-obese (10 females) individuals were
      exposed to incremental lower body negative pressure (LBNP) to presyncope while
      HR, arterial blood pressure, and cerebral perfusion (middle cerebral artery blood
      velocity; MCA V mean) were measured. OT was quantified with a cumulative stress
      index (CSI). RESULTS: OT was reduced in obese subjects, and there was an inverse
      relationship between body mass index (BMI) and OT (R = -0.47). HR was higher at
      rest and during each level of LBNP completed by all subjects. Similar peak HR
      (HRpeak) during LBNP between obese and non-obese subjects resulted in obese
      having a higher %peak HR at rest and at each stage of LBNP compared.
      Relationships existed for BMI and resting %HRpeak (R = 0.45) and resting %HRpeak
      and CSI (R = -0.52). Despite lower CSI in obese, MCA V mean and indices of
      cerebral autoregulation were similar between groups at all time points.
      CONCLUSIONS: These data suggest that OT is reduced in obese and a higher resting
      HR, but not impaired regulation of cerebral perfusion, may contribute to this
      reduction.

PMID- 24292892
TI  - Clinical validation of semi-automated software for volumetric and dynamic
      contrast enhancement analysis of soft tissue venous malformations on magnetic
      resonance imaging examination.
AB  - OBJECTIVES: To evaluate venous malformation (VM) volume and contrast-enhancement
      analysis on magnetic resonance imaging (MRI) compared with diameter evaluation.
      METHODS: Baseline MRI was undertaken in 44 patients, 20 of whom were followed by
      MRI after sclerotherapy. All patients underwent short-tau inversion recovery
      (STIR) acquisitions and dynamic contrast assessment. VM diameters in three
      orthogonal directions were measured to obtain the largest and mean diameters.
      Volumetric reconstruction of VM was generated from two orthogonal STIR sequences
      and fused with acquisitions after contrast medium injection. Reproducibility
      (interclass correlation coefficients [ICCs]) of diameter and volume measurements
      was estimated. VM size variations in diameter and volume after sclerotherapy and
      contrast enhancement before sclerotherapy were compared in patients with clinical
      success or failure. RESULTS: Inter-observer ICCs were similar for diameter and
      volume measurements at baseline and follow-up (range 0.87-0.99). Higher
      percentages of size reduction after sclerotherapy were observed with volume (32.6
      +/- 30.7%) than with diameter measurements (14.4 +/- 21.4%; P = 0.037). Contrast
      enhancement values were estimated at 65.3 +/- 27.5% and 84 +/- 13% in patients
      with clinical failure and success respectively (P = 0.056). CONCLUSIONS: Venous
      malformation volume was as reproducible as diameter measurement and more
      sensitive in detecting therapeutic responses. Patients with better clinical
      outcome tend to have stronger malformation enhancement. KEY POINTS: * Magnetic
      resonance imaging readily demonstrates diameters and volumes of venous
      malformations * MRI diameter calculations are reproducible in estimating the size
      of venous malformations * But volumetric models of malformations are more
      sensitive in detecting therapeutic response * Dynamic enhancement is also better
      assessed with automated volumetric software * Volumetric analysis of
      malformations offers promise to guide therapy and assess response.

PMID- 24292893
TI  - Design of novel leads: ligand based computational modeling studies on non
      nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1.
AB  - Researchers are on the constant lookout for new antiviral agents for the
      treatment of AIDS. In the present work, ligand based modeling studies are
      performed on analogues of substituted phenyl-thio-thymines, which act as non
      nucleoside reverse transcriptase inhibitors (NNRTIs) and novel leads are
      extracted. Using alignment-dependent descriptors, based on group center overlap
      (SALL, HDALL, HAALL and RALL), an alignment-independent descriptor (S log P), a
      topological descriptor (Balaban index (J)) and a 3D descriptor dipole moment (MU)
      and shape based descriptors (Kappa 2 index ((2)kappa)), a correlation is derived
      with inhibitory activity. Linear and non-linear techniques have been used to
      achieve the goal. Support Vector Machine (SVM, R = 0.929, R(2) = 0.863) and Back
      Propagation Neural Network (BPNN, R = 0.928, R(2) = 0.861) methods yielded near
      similar results and outperformed Multiple Linear Regression (MLR, R = 0.915, R(2)
      = 0.837). The predictive ability of the models are cross-validated using a test
      dataset (SVM: R = 0.846, R(2) = 0.716, BPNN: R = 0.841, R(2) = 0.707 and MLR: R =
      0.833, R(2) = 0.694). It is concluded that the hydrophobicity (S log P) and the
      polarity (MU) of a ligand and the presence of hydrogen donor (HDALL) moieties are
      the deciding factors in improving antiviral activity and pharmaco-therapeutic
      properties. Based on the above findings, a virtual dataset is created to extract
      probable leads with reasonable antiviral activity as well as better
      pharmacophoric properties.

PMID- 24292894
TI  - Change in electrodermal activity after acute tryptophan depletion associated with
      aggression in young people with attention deficit hyperactivity disorder (ADHD).
AB  - We investigated the impact of acute tryptophan depletion (ATD) and reduced brain
      serotonin synthesis on physiological arousal in 15 young people with ADHD
      participating in an aggression-inducing game. ATD was not associated with altered
      physiological arousal, as indexed by electrodermal activity (EDA). Baseline
      aggression was negatively correlated with the mean ATD effect on EDA. In
      accordance with the low arousal theory related to aggressive behavior, subjects
      with reduced physiological responsiveness/lower electrodermal reactivity to ATD
      tended to display elevated externalizing behavior. 

PMID- 24292895
TI  - Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the
      spectrum of Alzheimer's disease.
AB  - Increasing evidence links dysregulation of NR2B-containing N-methyl-D-aspartate
      receptor remodelling and trafficking to Alzheimer's disease (AD). This theme
      offers the possibility that the GRIN2B gene, encoding this selective NR2B
      subunit, represents a potential molecular modulating factor for this disease.
      Based on this hypothesis, we carried out a mutation scanning of exons and
      flanking regions of GRIN2B in a well-characterized cohort of AD patients,
      recruited from Southern Italy. A "de novo" p.K1293R mutation, affecting a highly
      conserved residue of the protein in the C-terminal domain, was observed for the
      first time in a woman with familial AD, as the only genetic alteration of
      relevance. Moreover, an association study between the other detected sequence
      variants and AD was performed. In particular, the study was focused on five
      identified single nucleotide polymorphisms: rs7301328, rs1805482, rs3026160,
      rs1806191 and rs1806201, highlighting a significant contribution from the GRIN2B
      rs1806201 T allele towards disease susceptibility [adjusted odds ratio (OR) =
      1.92, 95% confidence interval (CI) 1.40-2.63, p < 0.001, after correction for
      sex, age, and APOE epsilon4 genotype]. This was confirmed by haplotype analysis
      that identified a specific haplotype, carrying the rs1806201 T allele (CCCTC),
      over-represented in patients versus controls (adjusted OR = 6.03; p < 0.0001).
      Although the pathogenic role of the GRIN2B-K1293R mutation in AD is not clear,
      our data advocate that genetic variability in the GRIN2B gene, involved in
      synaptic functioning, might provide valuable insights into disease pathogenesis,
      continuing to attract significant attention in biomedical research on its genetic
      and functional role. 

PMID- 24292896
TI  - Public trust in genomic risk assessment for type 2 diabetes mellitus.
AB  - Patient trust in personal medical information is critical to increasing adherence
      to physician recommendations and medications. One of the anticipated benefits of
      learning of one's genomic risk for common diseases is the increased adoption of
      screening, preventive care and lifestyle changes. However, the equivocal results
      thus far reported of the positive impact of knowledge of genomic risk on behavior
      change may be due to lack of patients' trust in the results. As part of a
      clinical study to compare two methods of communication of genomic risk results
      for Type 2 diabetes mellitus (T2DM), we assessed patients' trust and preferred
      methods of delivery of genomic risk information. A total of 300 participants
      recruited from the general public in Durham, NC were randomized to receive their
      genomic risk for T2DM in-person from a genetic counselor or online through the
      testing company's web-site. Participants completed a baseline survey and three
      follow-up surveys after receiving results. Overall, participants reported high
      levels of trust in the test results. Participants who received their results in
      person from the genetic counselor were significantly more likely to trust their
      results than those who reviewed their results on-line (p = 0.005). There was not
      a statistically significant difference in levels of trust among participants with
      increased genetic risk, as compared to other those with decreased or same as
      population risk (p = 0.1154). In the event they undergo genomic risk testing
      again, 55 % of participants overall indicated they would prefer to receive their
      results online compared to 28 % that would prefer to receive future results in
      person. Of those participants preferring to receive results online, 77 %
      indicated they would prefer to have the option to speak to someone if they had
      questions with the online results (compared to accessing results online without
      the option of professional consultation). This is the first study to assess
      satisfaction with genomic risk testing by the method of delivery of the test
      result. The higher rate of trust in results delivered in-person suggests that
      online access reports may not result in serious consideration of results and lack
      of adoption of recommended preventive recommendations. 

PMID- 24292898
TI  - Association of aortic wall thickness on contrast-enhanced chest CT with major
      cerebro-cardiac events.
AB  - BACKGROUND: There is a significant association between aortic atherosclerosis and
      previous major cardiovascular events. Particularly, thoracic aortic
      atherosclerosis is closely related to the degree of coronary and carotid artery
      disease. Thus, there is a rationale for screening the thoracic aorta in patients
      who undergo a chest computed tomography (CT) for any clinical question, in order
      to detect patients at increased risk of cerebro-cardiovascular (CCV) events.
      PURPOSE: To estimate the association between either thoracic aortic wall
      thickness (AWT) or aortic total calcium score (ATCS) and CCV events. MATERIAL AND
      METHODS: One hundred and forty-eight non-cardiac patients (78 men; 67 +/- 12
      years) underwent chest contrast-enhanced multidetector CT (MDCT). The AWT was
      measured at the level of the left atrium (AWTref) and at the maximum AWT
      (AWTmax). Correlation with clinical CCV patients' history was estimated. The
      value of AWTmax and of a semi-quantitative ATCS as a marker for CCV events was
      assessed using receiver-operating characteristic curve (ROC) analysis and
      multivariate regression analysis. RESULTS: Out of 148 patients, 59% reported
      sedentary lifestyle, 44% hypertension, 32% smoking, 23% hypercholesterolemia, 13%
      family history of cardiac disease, 12% diabetes, and 10% BMI >= 30 kg/m(2); 9%
      reported myocardial infarction, 8% aortic aneurism, 8% myocardial
      revascularization, and 2% ischemic stroke. Twenty-six percent of patients had a
      medium-to-high ATCS. Both AWTmax and AWTref correlated with hypertension and age
      (P < 0.002). At the ROC analysis, a 4.8 mm threshold was associated to a 90%
      specificity and an odds ratio of 6.3 (AUC = 0.735). Assuming as threshold the
      AWTmax median value (4.3 mm) of patients who suffered from at least one CCV event
      in their history, a negative predictive value of 90%, a RR of 3.6 and an OR of
      6.3 were found. At the multivariate regression analysis, AWTmax was the only
      independent variable associated to the frequency of CCV events. CONCLUSION:
      Patients with increased thoracic AWTmax on chest MDCT could be considered at risk
      for CCV disease.

PMID- 24292897
TI  - Blockade of Nav1.8 currents in nociceptive trigeminal neurons contributes to anti
      trigeminovascular nociceptive effect of amitriptyline.
AB  - Amitriptyline (AMI), a tricyclic antidepressant, has been widely used to prevent
      migraine attacks and alleviate other various chronic pain, but the underlying
      mechanism remains unclear. Accumulated evidence suggests that the efficacy of AMI
      is related to the blockade of voltage-gated sodium channels. The aim of the
      present study was to investigate the effect of AMI on Na(v)1.8 currents in
      nociceptive trigeminal neurons and trigeminovascular nociception induced by
      electrical stimulation of the dura mater surrounding the superior sagittal sinus
      (SSS) in rats, as in the animal model of vascular headaches such as migraines.
      Using a whole-cell voltage recording technique, we showed that Na(v)1.8 currents
      were blocked by AMI in a concentration-dependent manner, with an IC50 value of
      6.82 MUM in acute isolated trigeminal ganglion neurons of the rats. AMI caused a
      hyperpolarizing shift in the voltage-dependent activation and steady-state
      inactivation and significantly blocked in a use-dependent manner and slowed the
      recovery from the inactivation of Na(v)1.8 currents. In addition, the systemic
      administration of AMI and A-803467 (a selective Na(v)1.8 channel blocker)
      potently alleviated the nociceptive behaviors (head flicks and grooming) induced
      by the electrical stimulation of the dura mater surrounding the SSS. Taken
      together, our data suggest that Na(v)1.8 currents in nociceptive trigeminal
      neurons are blocked by AMI through modulating the activation and inactivation
      kinetics, which may contribute to anti-nociceptive effect of AMI in animal models
      of migraines.

PMID- 24292899
TI  - Rabbit hepatic arterial anatomy variations: implications on experimental design.
AB  - BACKGROUND: The VX2 rabbit model of liver cancer is commonly used to evaluate the
      efficacy of locoregional anticancer therapy and knowledge of the hepatic arterial
      anatomy in the rabbit is important for catheter-directed experiments. PURPOSE: To
      describe the normal anatomy and anatomic variations of the celiac axis and
      hepatic artery in the rabbit. MATERIAL AND METHODS: Angiograms of 222 rabbits
      were retrospectively reviewed. The branching pattern of the celiac axis was
      classified and the diameters of the major branches were measured. Paired t-tests
      were used to compare the difference between the average sizes of arteries.
      RESULTS: Variant celiac axis or hepatic artery anatomy was noted in 25.9% of
      angiograms, with the gastric branches arising from the proper hepatic artery in
      23.3% of cases. The celiac axis could be successfully classified into one of five
      distinct branching patterns in 193 (86.9%) cases. The mean diameters of the right
      and left hepatic arteries were 0.67 mm (95% CI [0.64, 0.7]) and 1.25 mm (95% CI
      [1.19, 1.31]), respectively. The mean diameters of the medial and lateral
      branches of the left hepatic artery were 0.63 mm (95% CI [0.6, 0.67]) and 0.91 mm
      (95% CI [0.86, 0.96]), respectively. The right hepatic artery was significantly
      smaller than the left hepatic artery and the lateral branch of the left hepatic
      artery (all P values <0.0001). CONCLUSION: Arterial variants in the rabbit are
      not uncommon. The proper hepatic artery often gives origin to gastric artery
      branches. To facilitate superselective intra-arterial intervention, the left
      lateral lobe of the liver should be targeted for tumor implantation because of
      the significant size difference between the right and left hepatic arteries.

PMID- 24292900
TI  - Risk factors of radiation dose in patients undergoing peripherally-inserted
      central catheter procedure using conventional angiography equipment and flat
      panel detector-based mobile C-arm fluoroscopy.
AB  - BACKGROUND: Although peripherally-inserted central catheter (PICC) insertion is
      commonly performed under fluoroscopic guidance, few reports have addressed
      performance and dosimetry when PICC is inserted under C-arm fluoroscopy. PURPOSE:
      To evaluate the risk factors of radiation dose in performing PICC insertion using
      flat panel detector-based mobile C-arm fluoroscopy and a conventional angiography
      machine. MATERIAL AND METHODS: Ninety-eight patients underwent the PICC procedure
      using conventional angiography equipment (n=49) or flat panel detector-based
      mobile C-arm fluoroscopy (n=49). Data were prospectively analyzed from July to
      November 2012. Dose-area product (DAP), tube voltage, tube current, fluoroscopy
      time, and image quality measured on a 5-point scale were estimated and compared
      using appropriate statistical tests. RESULTS: There were no significant
      differences in tube voltage, fluoroscopy time, and image quality between
      conventional angiography and mobile C-arm fluoroscopy. DAP, mean arm tube
      current, and tube current in chest fluoroscopy were significantly lower in mobile
      C-arm fluoroscopy than using the conventional angiography machine (P < 0.05).
      Multivariate analysis identified tube current in chest fluoroscopy, arm tube
      current, and fluoroscopy equipment as significant risk factors for elevated
      radiation dose in PICC insertion. CONCLUSION: PICC insertion can be performed
      using flat panel detector-based mobile C-arm fluoroscopy instead of a
      conventional angiography machine. Image quality and fluoroscopy time were not
      different between the two systems and the use of C-arm fluoroscopy significantly
      reduced radiation dose.

PMID- 24292901
TI  - Screening of marine bacterial producers of polyunsaturated fatty acids and
      optimisation of production.
AB  - Water samples from three different environments including Mid Atlantic Ridge, Red
      Sea and Mediterranean Sea were screened in order to isolate new polyunsaturated
      fatty acids (PUFAs) bacterial producers especially eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA). Two hundred and fifty-one isolates were screened
      for PUFA production and among them the highest number of producers was isolated
      from the Mid-Atlantic Ridge followed by the Red Sea while no producers were found
      in the Mediterranean Sea samples. The screening strategy included a simple
      colourimetric method followed by a confirmation via GC/MS. Among the tested
      producers, an isolate named 66 was found to be a potentially high PUFA producer
      producing relatively high levels of EPA in particular. A Plackett-Burman
      statistical design of experiments was applied to screen a wide number of media
      components identifying glycerol and whey as components of a production medium.
      The potential low-cost production medium was optimised by applying a response
      surface methodology to obtain the highest productivity converting industrial by
      products into value-added products. The maximum achieved productivity of EPA was
      20 mg/g, 45 mg/l, representing 11% of the total fatty acids, which is
      approximately five times more than the amount produced prior to optimisation. The
      production medium composition was 10.79 g/l whey and 6.87 g/l glycerol. To our
      knowledge, this is the first investigation of potential bacteria PUFA producers
      from Mediterranean and Red Seas providing an evaluation of a colourimetric
      screening method as means of rapid screening of a large number of isolates.

PMID- 24292902
TI  - T cell responses: naive to memory and everything in between.

PMID- 24292904
TI  - Interactive mobile learning: a pilot study of a new approach for sport science
      and medical undergraduate students.
AB  - Mobile learning has increasingly become interwoven into the fabric of learning
      and teaching in the United Kingdom higher education sector, and as technological
      issues become addressed, this phenomena has accelerated. The aim of the study was
      to examine whether learning using a mobile learning device (Samsung NC10 Netbook)
      loaded with interactive exercises promoted learning compared with a traditional
      library exercise. Using a randomized trial, 55 students from an undergraduate
      sports science course (n = 28) and medical course (n = 27) volunteered to
      participate in this study. A mixed-model design ANOVA was used to examine the
      percent change in test score after a 3-wk intervention. Results showed that there
      was a significant difference between the two courses (P < 0.001), methods (P =
      0.01), and trials (P < 0.001). The findings suggested that both methods augmented
      student knowledge and understanding in sports science and medical students. The
      sports science group demonstrated proportionally greater increases in test
      performance when exposed to the mobile interactive intervention compared with the
      traditional library approach. Qualitative data suggest an increased level of
      engagement with the Netbooks due to the stimulating interactive content. In
      conclusion, the Netbooks were an effective additional learning tool,
      significantly enhancing knowledge and understanding in students. Further research
      should ensure that participants are assessed for preferred learning styles, the
      subjective task value of expectancy value, and readiness for mobile learning to
      ascertain if this has an effect on the potential for using mobile learning and
      interactivity. 

PMID- 24292905
TI  - Medical students' participation in and perception of unprofessional behaviors:
      comparison of preclinical and clinical phases.
AB  - We aimed to compare reported observations, participation in, and perceptions of
      unprofessional behaviors across preclinical and clinical medical students using a
      23-item questionnaire that asked participants whether they witnessed or
      participated in the behavior and considered it unprofessional. Overall, 111
      preclinical (year 3) and 104 clinical (year 4) students responded. For all of the
      behaviors, significant positive correlations were present between participation
      and affirmative perceptions. Participation rates for several unprofessional
      behaviors (14 of 23 items) were higher in the clinical phase. Clinical students
      more frequently perceived unprofessional behaviors as appropriate (17 of 23
      items) compared with preclinical students. In conclusion, both preclinical and
      clinical medical students in our setting commonly witness unprofessional
      behaviors. Clinical students participate in and tend to rationalize these
      behaviors more frequently than preclinical students do. 

PMID- 24292903
TI  - Pattern recognition receptors in innate immunity, host defense, and
      immunopathology.
AB  - Infection by pathogenic microbes initiates a set of complex interactions between
      the pathogen and the host mediated by pattern recognition receptors. Innate
      immune responses play direct roles in host defense during the early stages of
      infection, and they also exert a profound influence on the generation of the
      adaptive immune responses that ensue. An improved understanding of the pattern
      recognition receptors that mediate innate responses and their downstream effects
      after receptor ligation has the potential to lead to new ways to improve vaccines
      and prevent autoimmunity. This review focuses on the control of innate immune
      activation and the role that innate immune receptors play in helping to maintain
      tissue homeostasis. 

PMID- 24292906
TI  - A set of vertically integrated inquiry-based practical curricula that develop
      scientific thinking skills for large cohorts of undergraduate students.
AB  - Science graduates require critical thinking skills to deal with the complex
      problems they will face in their 21st century workplaces. Inquiry-based curricula
      can provide students with the opportunities to develop such critical thinking
      skills; however, evidence suggests that an inappropriate level of autonomy
      provided to underprepared students may not only be daunting to students but also
      detrimental to their learning. After a major review of the Bachelor of Science,
      we developed, implemented, and evaluated a series of three vertically integrated
      courses with inquiry-style laboratory practicals for early-stage undergraduate
      students in biomedical science. These practical curricula were designed so that
      students would work with increasing autonomy and ownership of their research
      projects to develop increasingly advanced scientific thinking and communication
      skills. Students undertaking the first iteration of these three vertically
      integrated courses reported learning gains in course content as well as skills in
      scientific writing, hypothesis construction, experimental design, data analysis,
      and interpreting results. Students also demonstrated increasing skills in both
      hypothesis formulation and communication of findings as a result of participating
      in the inquiry-based curricula and completing the associated practical assessment
      tasks. Here, we report the specific aspects of the curricula that students
      reported as having the greatest impact on their learning and the particular
      elements of hypothesis formulation and communication of findings that were more
      challenging for students to master. These findings provide important implications
      for science educators concerned with designing curricula to promote scientific
      thinking and communication skills alongside content acquisition. 

PMID- 24292907
TI  - Flipped classroom model improves graduate student performance in cardiovascular,
      respiratory, and renal physiology.
AB  - The purpose of this study was to assess the effectiveness of a traditional
      lecture-based curriculum versus a modified "flipped classroom" curriculum of
      cardiovascular, respiratory, and renal physiology delivered to first-year
      graduate students. Students in both courses were provided the same notes and
      recorded lectures. Students in the modified flipped classroom were required to
      watch the prerecorded lectures before class and then attend class, where they
      received a quiz or homework covering material in each lecture (valued at 25% of
      the final grade) followed by a question and answer/problem-solving period. In the
      traditional curriculum, attending lectures was optional and there were no
      quizzes. Evaluation of effectiveness and student performance was achieved by
      having students in both courses take the same multiple-choice exams. Within a
      comparable group of graduate students, participants in the flipped course scored
      significantly higher (P <= 0.05) on the cardiovascular, respiratory, and weighted
      cumulative sections by an average of >12 percentage points. Exam averages for
      students in the flipped course also tended to be higher on the renal section by
      ~11 percentage points (P = 0.06). Based on our experience and responses obtained
      in blinded student surveys, we propose that the use of homework and in-class
      quizzes were critical motivating factors that likely contributed to the increase
      in student exam performance. Taken together, our findings support that the
      flipped classroom model is a highly effective means in which to disseminate key
      physiological concepts to graduate students. 

PMID- 24292908
TI  - A novel laboratory approach for the demonstration of hemodynamic principles: the
      arterial blood flow reflection.
AB  - In the frame of a laboratory training course for medicine students, a new
      approach for laboratory exercises has been applied to teach the phenomena of
      circulation. The exercise program included measurements of radial artery blood
      flow waveform for different age groups using a noninvasive optical sensor.
      Arterial wave reflection was identified by measurements of blood flow waveforms
      before and after arterial branching. Students were able to distinguish between
      different waveforms of blood flow within different age groups. Furthermore,
      students were given the opportunity to explore the effect of aging on the
      elasticity of blood vessels. This exercise is an introduction to the fundamental
      physical laws of hemodynamics that can facilitate the learning and understanding
      of cardiovascular physiology to students of medicine. 

PMID- 24292909
TI  - A novel approach to teach the generation of bioelectrical potentials from a
      descriptive and quantitative perspective.
AB  - In electrophysiology studies, it is becoming increasingly common to explain
      experimental observations using both descriptive methods and quantitative
      approaches. However, some electrophysiological phenomena, such as the generation
      of extracellular potentials that results from the propagation of the excitation
      source along the muscle fiber, are difficult to describe and conceptualize. In
      addition, most traditional approaches aimed at describing extracellular
      potentials consist of complex mathematical machinery that gives no chance for
      physical interpretation. The aim of the present study is to present a new method
      to teach the formation of extracellular potentials around a muscle fiber from
      both a descriptive and quantitative perspective. The implementation of this
      method was tested through a written exam and a satisfaction survey. The new
      method enhanced the ability of students to visualize the generation of
      bioelectrical potentials. In addition, the new approach improved students'
      understanding of how changes in the fiber-to-electrode distance and in the shape
      of the excitation source are translated into changes in the extracellular
      potential. The survey results show that combining general principles of
      electrical fields with accurate graphic imagery gives students an intuitive, yet
      quantitative, feel for electrophysiological signals and enhances their motivation
      to continue their studies in the biomedical engineering field. 

PMID- 24292910
TI  - Introducing e-learning/teaching in a physiology course for medical students:
      acceptance by students and subjective effect on learning.
AB  - Retrieval of information has substantially changed within the last two decades.
      Naturally, this has also affected learning/teaching techniques, and methods that
      are commonly referred to as "e-learning" have become an important part in modern
      education. Institutions have to decide if (and how) to implement this new form of
      teaching but face the problem that little subject-specific research has been
      published for different teaching modes and methods. The present study compares a
      course module of the physiology laboratory course for medical students in the
      preclinical phase before and after the introduction of computer-aided course
      instructions (CACI). Students were provided with an online questionnaire
      containing Likert items evaluating workspace redesign, acceptance of course
      instructions, incentive to actively participate in the course, and subjective
      gain of knowledge. CACI was clearly preferred over the previously used paper
      workbook. However, the questionnaire also revealed that the gain in knowledge, as
      subjectively perceived by the students, had not improved, which is in agreement
      with several studies that neglected a beneficial effect of e-learning on learning
      success. We conclude that the CACI meet today's student's expectations and that
      introducing this system seems justified from this perspective. 

PMID- 24292911
TI  - An inexpensive 2-D and 3-D model of the sarcomere as a teaching aid.
AB  - To address a common problem of teaching the sliding filament theory (that is,
      students have difficulty in visualizing how the component proteins of the
      sarcomere differ, how they organize themselves into a single working unit, and
      how they function in relation to each other), we have devised a simple model,
      with inexpensive materials, to be built by students in the fourth year of an
      undergraduate biology course. This model can be quickly built by the students
      themselves and is functional enough to allow visualization of the filaments and
      their properties. The model uses cheap, simple materials, mostly party and craft
      supplies, to simulate the component proteins of the sarcomere, and the proposed
      materials can be readily replaced by more available ones. 

PMID- 24292912
TI  - A comparison of traditional and engaging lecture methods in a large, professional
      level course.
AB  - In engaging lectures, also referred to as broken or interactive lectures,
      students are given short periods of lecture followed by "breaks" that can consist
      of 1-min papers, problem sets, brainstorming sessions, or open discussion. While
      many studies have shown positive effects when engaging lectures are used in
      undergraduate settings, the literature surrounding use of the learning technique
      for professional students is inconclusive. The novelty of this study design
      allowed a direct comparison of engaging physiology lectures versus didactic
      lecture formats in the same cohort of 120 first-year School of Dentistry DMD
      students. All students were taught five physiological systems using traditional
      lecture methods and six physiological systems using engaging lecture methods. The
      use of engaging lectures led to a statistically significant higher average on
      unit exams compared with traditional didactic lectures (8.6% higher, P < 0.05).
      Furthermore, students demonstrated an improved long-term retention of information
      via higher scores on the comprehensive final exam (22.9% higher in engaging
      lecture sections, P < 0.05). Many qualitative improvements were also indicated
      via student surveys and evaluations, including an increased perceived
      effectiveness of lectures, decrease in distractions during lecture, and increased
      confidence with the material. The development of engaging lecture activities
      requires a significant amount of instructor preparation and limits the time
      available to provide traditional lectures. However, the positive results of this
      study suggest the need for a restructuring of the physiology curriculum to
      incorporate more engaging lectures to improve both the qualitative experiences
      and performance levels of professional students. 

PMID- 24292913
TI  - Case-based learning in endocrine physiology: an approach toward self-directed
      learning and the development of soft skills in medical students.
AB  - The Medical Council of India, in the recent Vision 2015 document, recommended
      curricular reforms for undergraduates. Case-based learning (CBL) is one method
      where students are motivated toward self-directed learning and to develop
      analytic and problem-solving skills. An overview of thyroid physiology was given
      in a didactic lecture. A paper-based case scenario of multinodular goiter was
      given to phase I Bachelor of Medicine, Bachelor of Surgery students in two
      sessions. An attitude survey of the students and teachers was done using a Likert
      scale ranging from strongly disagrees to strongly agree. A pretest and posttest
      were conducted. The students opined that CBL helped them to better their
      understanding of a particular topic, gave them better retention of knowledge,
      helped them to relate clinical conditions to basic sciences, improved soft skills
      such as communication skills and group dynamics, and promoted a better teacher
      student relationship. There was significant improvement in student's performance
      when pre- and posttest scores were compared (P = 0.018). Furthermore, faculty
      members opined that CBL promoted self-study and problem-solving abilities of the
      students. In conclusion, CBL motivates students toward self-directed learning and
      to develop analytic and problem-solving skills; thus, CBL could be beneficial for
      students' entry into clinical departments and, finally, in managing patients. 

PMID- 24292914
TI  - CO(2) rebreathing: an undergraduate laboratory to study the chemical control of
      breathing.
AB  - The Read CO2 rebreathing method (Read DJ. A clinical method for assessing the
      ventilatory response to carbon dioxide. Australas Ann Med 16: 20-32, 1967)
      provides a simple and reproducible approach for studying the chemical control of
      breathing. It has been widely used since the modifications made by Duffin and
      coworkers. Our use of a rebreathing laboratory to challenge undergraduate science
      students to investigate the control of breathing provided 8 yr of student
      generated data for comparison with the literature. Students (age: 19-22 yr,
      Research Ethics Board approval) rebreathed from a bag containing 5% CO2 and 95%
      O2 (to suppress the peripheral chemoreflex to hypoxia). Rebreathing was
      performed, and ventilation measured, after hyperventilation to deplete tissue CO2
      stores and enable the detection of the central chemoreflex threshold. We analyzed
      43 data sets, of which 10 were rejected for technical reasons. The mean threshold
      and ventilatory sensitivity to CO2 were 43.3 +/- 3.8 mmHg and 4.60 +/- 3.04
      l.min(-1).mmHg(-1) (means +/- SD), respectively. Threshold values were normally
      distributed, whereas sensitivity was skewed to the left. Both mean values agreed
      well with those in the literature. We conclude that the modified rebreathing
      protocol is a robust method for undergraduate investigation of the chemical
      control of breathing. 

PMID- 24292915
TI  - A comparison of student performance on discipline-specific versus integrated
      exams in a medical school course.
AB  - Curricular reform is a widespread trend among medical schools. Assessing the
      impact that pedagogical changes have on students is a vital step in review
      process. This study examined how a shift from discipline-focused instruction and
      assessment to integrated instruction and assessment affected student performance
      in a second-year medical school pathology course. We investigated this by
      comparing pathology exam scores between students exposed to traditional
      discipline-specific instruction and exams (DSE) versus integrated instruction and
      exams (IE). Exam content was controlled, and individual questions were evaluated
      using a modified version of Bloom's taxonomy. Additionally, we compared United
      States Medical Licensing Examination (USMLE) step 1 scores between DSE and IE
      groups. Our findings indicate that DSE students performed better than IE students
      on complete pathology exams. However, when exam content was controlled, exam
      scores were equivalent between groups. We also discovered that the integrated
      exams were composed of a significantly greater proportion of questions classified
      on the higher levels of Bloom's taxonomy and that IE students performed better on
      these questions overall. USMLE step 1 exam scores were similar between groups.
      The finding of a significant difference in content complexity between discipline
      specific and integrated exams adds to recent literature indicating that there are
      a number of potential biases related to curricular comparison studies that must
      be considered. Future investigation involving larger sample sizes and multiple
      disciplines should be performed to explore this matter further. 

PMID- 24292916
TI  - Animal galloping and human hopping: an energetics and biomechanics laboratory
      exercise.
AB  - This laboratory exercise demonstrates fundamental principles of mammalian
      locomotion. It provides opportunities to interrogate aspects of locomotion from
      biomechanics to energetics to body size scaling. It has the added benefit of
      having results with robust signal to noise so that students will have success
      even if not "meticulous" in attention to detail. First, using respirometry,
      students measure the energetic cost of hopping at a "preferred" hop frequency.
      This is followed by hopping at an imposed frequency half of the preferred. By
      measuring the O2 uptake and work done with each hop, students calculate
      mechanical efficiency. Lessons learned from this laboratory include 1) that the
      metabolic cost per hop at half of the preferred frequency is nearly double the
      cost at the preferred frequency; 2) that when a person is forced to hop at half
      of their preferred frequency, the mechanical efficiency is nearly that predicted
      for muscle but is much higher at the preferred frequency; 3) that the preferred
      hop frequency is strongly body size dependent; and 4) that the hop frequency of a
      human is nearly identical to the galloping frequency predicted for a quadruped of
      our size. Together, these exercises demonstrate that humans store and recover
      elastic recoil potential energy when hopping but that energetic savings are
      highly frequency dependent. This stride frequency is dependent on body size such
      that frequency is likely chosen to maximize this function. Finally, by requiring
      students to make quantitative solutions using appropriate units and dimensions of
      the physical variables, these exercises sharpen analytic and quantitative skills.

PMID- 24292917
TI  - Measuring dynamic kidney function in an undergraduate physiology laboratory.
AB  - Most undergraduate physiology laboratories are very limited in how they treat
      renal physiology. It is common to find teaching laboratories equipped with the
      capability for high-resolution digital recordings of physiological functions
      (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most
      urinary laboratories still rely on a "dipstick" approach of urinalysis. Although
      this technique can provide some basic insights into the functioning of the
      kidneys, it overlooks the dynamic processes of filtration, reabsorption, and
      secretion. In the present article, we provide a straightforward approach of using
      renal clearance measurements to estimate glomerular filtration rate, fractional
      water reabsorption, glucose clearance, and other physiologically relevant
      parameters. The estimated values from our measurements in laboratory are in close
      agreement with those anticipated based on textbook parameters. For example, we
      found glomerular filtration rate to average 124 +/- 45 ml/min, serum creatinine
      to be 1.23 +/- 0.4 mg/dl, and fractional water reabsorption to be ~96.8%.
      Furthermore, analyses for the class data revealed significant correlations
      between parameters like fractional water reabsorption and urine concentration,
      providing opportunities to discuss urine concentrating mechanisms and other
      physiological processes. The procedures outlined here are general enough that
      most undergraduate physiology laboratory courses should be able to implement them
      without difficulty. 

PMID- 24292918
TI  - Ion permeability of artificial membranes evaluated by diffusion potential and
      electrical resistance measurements.
AB  - In the present article, a novel model of artificial membranes that provides
      efficient assistance in teaching the origins of diffusion potentials is proposed.
      These membranes are made of polycarbonate filters fixed to 12-mm plastic rings
      and then saturated with a mixture of creosol and n-decane. The electrical
      resistance and potential difference across these membranes can be easily measured
      using a low-cost volt-ohm meter and home-made Ag/AgCl electrodes. The advantage
      of the model is the lack of ionic selectivity of the membrane, which can be
      modified by the introduction of different ionophores to the organic liquid
      mixture. A membrane treated with the mixture containing valinomycin generates
      voltages from -53 to -25 mV in the presence of a 10-fold KCl gradient (in to out)
      and from -79 to -53 mV in the presence of a bi-ionic KCl/NaCl gradient (in to
      out). This latter bi-ionic gradient potential reverses to a value from +9 to +20
      mV when monensin is present in the organic liquid mixture. Thus, the model can be
      build stepwise, i.e., all factors leading to the development of diffusion
      potentials can be introduced sequentially, helping students to understand the
      quantitative relationships of ionic gradients and differential membrane
      permeability in the generation of cell electrical signals. 

PMID- 24292919
TI  - Investigating autonomic control of the cardiovascular system: a battery of simple
      tests.
AB  - Sympathetic and parasympathetic divisions of the autonomic nervous system
      constantly control the heart (sympathetic and parasympathetic divisions) and
      blood vessels (predominantly the sympathetic division) to maintain appropriate
      blood pressure and organ blood flow over sometimes widely varying conditions.
      This can be adversely affected by pathological conditions that can damage one or
      both branches of autonomic control. The set of teaching laboratory activities
      outlined here uses various interventions, namely, 1) the heart rate response to
      deep breathing, 2) the heart rate response to a Valsalva maneuver, 3) the heart
      rate response to standing, and 4) the blood pressure response to standing, that
      cause fairly predictable disturbances in cardiovascular parameters in normal
      circumstances, which serve to demonstrate the dynamic control of the
      cardiovascular system by autonomic nerves. These tests are also used clinically
      to help investigate potential damage to this control. 

PMID- 24292920
TI  - An active learning mammalian skeletal muscle lab demonstrating contractile and
      kinetic properties of fast- and slow-twitch muscle.
AB  - The fact that humans possess fast- and slow-twitch muscle in the ratio of ~50%
      has profound implications for designing exercise training strategies for power
      and endurance activities. With the growth of exercise and sport science courses,
      we have seen the need to develop an undergraduate student laboratory that
      demonstrates the basic properties of fast- and slow-twitch mammalian skeletal
      muscle. This laboratory illustrates the major differences in contractile
      properties and fatigue profiles exhibited by the two muscle types. Students
      compare and contrast twitch kinetics, fused tetanus characteristics, force
      frequency relationships, and fatigue properties of fast- and slow-twitch muscles.
      Examples of results collected by students during class are used to illustrate the
      type of data collected and analysis performed. During the laboratory, students
      are encouraged to connect factual information from their skeletal muscle lectures
      to their laboratory findings. This enables student learning in an active fashion;
      in particular, the isolated muscle preparation demonstrates that much of what
      makes muscle fast or slow is myogenic and not the product of the nervous or
      circulatory systems. This has far-reaching implications for motor control and
      exercise behavior and therefore is a crucial element in exercise science, with
      its focus on power and endurance sport activities. To measure student
      satisfaction with this active learning technique, a questionnaire was
      administered after the laboratory; 96% of the comments were positive in their
      support of active versus passive learning strategies. 

PMID- 24292921
TI  - Glucose transport into everted sacs of the small intestine of mice.
AB  - The Na(+)-glucose cotransporter is a key transport protein that is responsible
      for absorbing Na(+) and glucose from the luminal contents of the small intestine
      and reabsorption by the proximal straight tubule of the nephron. Robert K. Crane
      originally described the cellular model of absorption of Na(+) and glucose by a
      "cotransport process" in 1960. Over the past 50+ yr, numerous groups have tested
      and verified Crane's hypothesis. Eventually, Wright and colleagues cloned the
      Na(+)-glucose cotransporter (SGLT1; the product of the SLC5A1 gene) in 1987. This
      article provides a "hands-on" laboratory exercise using the everted mouse jejunal
      preparation (everted sac) that allows students to investigate various components
      of the Na(+)-glucose cotransport absorptive cell model (e.g., Na(+) dependence of
      SGLT1, inhibition of SGLT1, and inhibition of Na(+)-K(+)-ATPase). Additionally,
      the laboratory exercise includes a case-based study of glucose-galactose
      malabsorption in which the students conduct an internet search and participate in
      a small-group discussion during the laboratory period to better understand the
      basic principles and functions of the Na(+)-glucose absorptive process of the
      small intestine. This laboratory exercise was introduced into the second-year
      undergraduate physiology curriculum in 2008, and >850 physiology students have
      participated in this laboratory exercise. The students have produced very robust
      and reproducible data that clearly illustrate the theory of the cellular model
      for Na(+)-glucose absorption by the jejunum. 

PMID- 24292922
TI  - An educational device for a hands-on activity to visualize the effect of
      atherosclerosis on blood flow.
AB  - An educational device was created to develop a hands-on activity to illustrate
      how atherosclerosis can dramatically reduce blood flow in human vessels. The
      device was conceived, designed, and built at the University of Coimbra, in
      response to a request from the Exploratorio Infante D. Henrique Science Centre
      Museum, where it is presently installed. The device was designed to allow lay
      audience to operate it, including school-age youngsters. The two blood flow
      reduction mechanisms that can be visualized are 1) thickening of the artery wall
      and 2) hardening of the artery wall. The main objective is to promote the
      understanding of atherosclerotic cardiovascular physiology by simple and direct
      experiments. This original educational interactive device was constructed using,
      in the conceptual and design stages of the project, a Newtonian theoretical flow
      model based on Poiseuille's equation. This device is driven by human force and
      provides a visualization of the effect of atherosclerosis on flow. The main
      aspects relating to its design and construction are described here to explain and
      disseminate this approach. Throughout more than 4 yr of real operation, this
      educational device proved to be a simple and attractive way of understanding
      atherosclerosis, especially among young people. 

PMID- 24292923
TI  - Training TAs in scientific teaching for the human physiology and anatomy
      laboratory.

PMID- 24292924
TI  - Student construction of anatomic models for learning complex, seldom seen
      structures.

PMID- 24292925
TI  - Mongolian pines (Pinus sylvestris var. mongolica) in the Hulun Buir steppe,
      China, respond to climate in adjustment to the local water supply.
AB  - The growth response of Mongolian pine (Pinus sylvestris var. mongolica) to
      climate was studied at three sites in the Hulun Buir steppe on the eastern
      Mongolian Plateau, China. Correlation analysis revealed two patterns of response:
      (1) trees on two sites in the upstream section of the Yimin River are strongly
      limited by temperature and precipitation during the growing season from April to
      September, and (2) trees in the convergence area of the downstream section of the
      Yimin River and of the midstream section of the Hailar River are sensitive to
      precipitation during winter (December-January) and early spring (April) as well
      as to the early growing season temperature (April and June). These responses can
      be attributed to the positions where groundwater, recharged by the runoff from
      summer to autumn (July-September), could supply sufficient water needed for tree
      growth. Therefore, the patterns of growth-climate responses and of climate
      variation trends in this steppe region should be considered for the management
      and afforestation of Mongolian pines. 

PMID- 24292927
TI  - Pediatric thoracolumbar spine trauma.
AB  - Thoracolumbar spine trauma is an important cause of morbidity and mortality in
      pediatric patients. Special attention to this population is necessary because
      several unique features of the growing pediatric spine separate these patients
      from adult patients. These injuries are frequently associated with high-energy
      trauma and concurrent thoracic or abdominal injuries that require coordinated
      multidisciplinary care. Thoracolumbar spine trauma in pediatric patients may lead
      to compression fractures, burst fractures, flexion-distraction injuries (ie,
      Chance fracture), fracture-dislocation injuries, apophyseal
      fractures/herniations, and spinous process and transverse process fractures.
      Depending on the nature of the injury and the patient's level of skeletal
      maturity, thoracolumbar spinal injuries may have substantial ability to heal and
      remodel. Because the impact of thoracolumbar spinal injury on pediatric patients
      can be devastating, appropriate early diagnosis and management, as well as long
      term follow-up, are imperative. 

PMID- 24292928
TI  - Iatrogenic nerve injuries in shoulder surgery.
AB  - The range of open and arthroscopic shoulder procedures continues to evolve and
      expand. Despite advances in instrumentation and technology, complications still
      exist and neurologic injury remains an inherent part of these procedures.
      Iatrogenic nerve injuries are among the more commonly cited complications
      associated with shoulder surgery. Various surgical procedures about the shoulder
      are known to place the brachial plexus and peripheral motor nerves at risk.
      Peripheral nerve monitoring has been helpful in identifying specific surgical
      steps and key anatomic regions that are susceptible to iatrogenic nerve injury. 

PMID- 24292926
TI  - In vivo antioxidative and neuroprotective effect of 4-Allyl-2-methoxyphenol
      against chlorpyrifos-induced neurotoxicity in rat brain.
AB  - Chlorpyrifos exposure leads to various neurological disorders adverting
      disturbance in molecular pathways and normal brain functions. Major complications
      arise when these potent nerve agents access neuronal mechanisms causing adverse
      effect on acetylcholinesterase and brain lipids with generation of reactive
      oxygen species. Chlorpyrifos elicits chronic intoxication leading to redox
      disturbance with irreversible brain damage and oxidative stress. In the present
      study, neuroprotective and anti-apoptotic effects of eugenol (EO), a phenolic
      antioxidant, against chlorpyrifos-induced neurotoxicity was explored on rat brain
      cortex. Rats treated orally with chlorpyrifos [89.4 mg/kg body weight (BW)] for
      15 consecutive days showed changes in brain lipid profile, increased levels of
      lipid peroxidation, inhibition of acetylcholinesterase activity, and changes in
      antioxidant enzymes. EO (250 mg/kg BW), administered 1 h after chlorpyrifos
      treatment, restored lipid, acetylcholinesterase, and antioxidant enzyme levels of
      brain cortex by suppressing chlorpyrifos-induced oxidative stress and
      neurotoxicity. Histological findings further demonstrated damage to brain
      morphology with increased protein levels of caspase-3 in CPF-treated animals.
      Alterations caused by neurotoxic effects of chlorpyrifos were attenuated by EO
      administration with decreased protein expressions of caspase-3. Thus, through its
      antioxidant and anti-apoptotic activities, EO showed protective effect against
      chlorpyrifos-induced neuronal damage. 

PMID- 24292929
TI  - Early weight bearing after lower extremity fractures in adults.
AB  - Weight-bearing protocols should optimize fracture healing while avoiding fracture
      displacement or implant failure. Biomechanical and animal studies indicate that
      early loading is beneficial, but high-quality clinical studies comparing weight
      bearing protocols after lower extremity fractures are not universally available.
      For certain fracture patterns, well-designed trials suggest that patients with
      normal protective sensation can safely bear weight sooner than most protocols
      permit. Several randomized, controlled trials of surgically treated ankle
      fractures have shown no difference in outcomes between immediate and delayed (>=6
      weeks) weight bearing. Retrospective series have reported low complication rates
      with immediate weight bearing following intramedullary nailing of femoral shaft
      fractures and following surgical management of femoral neck and intertrochanteric
      femur fractures in elderly patients. For other fracture patterns, particularly
      periarticular fractures, the evidence in favor of early weight bearing is less
      compelling. Most surgeons recommend a period of protected weight bearing for
      patients with calcaneal, tibial plafond, tibial plateau, and acetabular
      fractures. Further studies are warranted to better define optimal postoperative
      weight-bearing protocols. 

PMID- 24292930
TI  - Platelet-rich plasma in orthopaedic applications: evidence-based recommendations
      for treatment.
AB  - Autologous platelet-rich plasma (PRP) therapies have seen a dramatic increase in
      breadth and frequency of use for orthopaedic conditions in the past 5 years. Rich
      in many growth factors that have important implications in healing, PRP can
      potentially regenerate tissue via multiple mechanisms. Proposed clinical and
      surgical applications include spinal fusion, chondropathy, knee osteoarthritis,
      tendinopathy, acute and chronic soft-tissue injuries, enhancement of healing
      after ligament reconstruction, and muscle strains. However, for many conditions,
      there is limited reliable clinical evidence to guide the use of PRP. Furthermore,
      classification systems and identification of differences among products are
      needed to understand the implications of variability. 

PMID- 24292931
TI  - Adhesive capsulitis of the hip: a review.
AB  - Adhesive capsulitis of the hip (ACH) is a rare clinical entity. Similar to
      adhesive capsulitis of the shoulder, ACH is characterized by a painful decrease
      in active and passive range of motion as synovial inflammation in the acute
      stages of the disease progresses to capsular fibrosis in the chronic stages. Once
      other diagnoses have been ruled out, management of ACH is tailored to reduce
      inflammation in the acute stages with NSAIDs, intra-articular steroid injections,
      and targeted physical therapy while biomechanical dysfunction in the spine, hip,
      sacroiliac joint, or lower limb joints is addressed. In chronic stages of the
      disease, intervention should focus on decreasing the progression of fibrotic
      changes and regaining range of motion through aggressive physical therapy.
      Interventions described for chronic ACH include manipulation under anesthesia;
      pressure dilatation; and open or arthroscopic synovectomy, lysis of adhesions,
      and capsular release. Surgical intervention should be considered only after
      failure of a minimum 3-month course of nonsurgical treatment. 

PMID- 24292932
TI  - Fingertip injuries: an update on management.
AB  - Injuries to the fingertip are common. The goal of treatment is restoration of a
      painless, functional digit with protective sensation. The amount of soft-tissue
      loss, the integrity of the nail bed, and the age and physical demands of the
      patient should be considered when selecting a treatment method. Some new products
      are effective for management of injuries to the fingertip. The use of 2
      octylcyanoacrylate for nail bed repair is faster than suture repair, with
      equivalent results reported. Dermal regeneration template is effective for
      coverage of digital injuries with exposed tendons or bones that lack peritenon or
      periosteum. Although fingertip replantation offers better functional results than
      does revision amputation, replantation is more technically demanding and requires
      longer recovery time. Complications associated with management of injuries to the
      fingertip include nail deformities, insensate digits, and painful neuromas. 

PMID- 24292933
TI  - Optimizing the management of full-thickness rotator cuff tears.
AB  - The American Academy of Orthopaedic Surgeons has developed Appropriate Use
      Criteria (AUC) on Optimizing the Management of Full-Thickness Rotator Cuff Tears
      (RC). Evidence-based information, in conjunction with clinical expertise of
      physicians, was used to develop the criteria to improve patient care and obtain
      best outcomes while considering the subtleties and distinctions necessary in
      making clinical decisions. The RC AUC Writing Panel began the development of the
      clinical scenarios by identifying clinical indications typical of patients
      commonly presenting with full-thickness rotator cuff tears in clinical practice,
      as well as from the current evidence-based clinical practice guidelines and its
      supporting literature. The 432 patient scenarios and 5 treatments were developed
      by the Writing Panel, a group of clinicians who are specialists in this AUC
      topic. Next, the Review Panel, a separate group of volunteer physicians,
      independently reviewed these materials to ensure that they were representative of
      patient scenarios that clinicians are likely to encounter in daily practice.
      Finally, the multidisciplinary Voting Panel (made up of specialists and
      nonspecialists) rated the appropriateness of treatment of each patient scenario
      using a 9-point scale to designate a treatment as appropriate (median rating, 7
      to 9), may be appropriate (median rating, 4 to 6), or rarely appropriate (median
      rating, 1 to 3). 

PMID- 24292934
TI  - AAOS appropriate use criteria: optimizing the management of full-thickness
      rotator cuff tears.

PMID- 24292935
TI  - Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential
      coexpression test for gene sets.
AB  - MOTIVATION: To date, gene set analysis approaches primarily focus on identifying
      differentially expressed gene sets (pathways). Methods for identifying
      differentially coexpressed pathways also exist but are mostly based on aggregated
      pairwise correlations or other pairwise measures of coexpression. Instead, we
      propose Gene Sets Net Correlations Analysis (GSNCA), a multivariate differential
      coexpression test that accounts for the complete correlation structure between
      genes. RESULTS: In GSNCA, weight factors are assigned to genes in proportion to
      the genes' cross-correlations (intergene correlations). The problem of finding
      the weight vectors is formulated as an eigenvector problem with a unique
      solution. GSNCA tests the null hypothesis that for a gene set there is no
      difference in the weight vectors of the genes between two conditions. In
      simulation studies and the analyses of experimental data, we demonstrate that
      GSNCA captures changes in the structure of genes' cross-correlations rather than
      differences in the averaged pairwise correlations. Thus, GSNCA infers differences
      in coexpression networks, however, bypassing method-dependent steps of network
      inference. As an additional result from GSNCA, we define hub genes as genes with
      the largest weights and show that these genes correspond frequently to major and
      specific pathway regulators, as well as to genes that are most affected by the
      biological difference between two conditions. In summary, GSNCA is a new approach
      for the analysis of differentially coexpressed pathways that also evaluates the
      importance of the genes in the pathways, thus providing unique information that
      may result in the generation of novel biological hypotheses. AVAILABILITY AND
      IMPLEMENTATION: Implementation of the GSNCA test in R is available upon request
      from the authors.

PMID- 24292936
TI  - Accessibility of microRNA binding sites in metastable RNA secondary structures in
      the presence of SNPs.
AB  - MOTIVATION: We study microRNA (miRNA) bindings to metastable RNA secondary
      structures close to minimum free energy conformations in the context of single
      nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) concentration levels,
      i.e. whether features of miRNA bindings to metastable conformations could provide
      additional information supporting the differences in expression levels of the two
      sequences defined by a SNP. In our study, the instances [mRNA/3'UTR; SNP; miRNA]
      were selected based on strong expression level analyses, SNP locations within
      binding regions and the computationally feasible identification of metastable
      conformations. RESULTS: We identified 14 basic cases [mRNA; SNP; miRNA] of 3' UTR
      lengths ranging from 124 up to 1078 nt reported in recent literature, and we
      analyzed the number, structure and miRNA binding to metastable conformations
      within an energy offset above mfe conformations. For each of the 14 instances,
      the miRNA binding characteristics are determined by the corresponding STarMir
      output. Among the different parameters we introduced and analyzed, we found that
      three of them, related to the average depth and average opening energy of
      metastable conformations, may provide supporting information for a stronger
      separation between miRNA bindings to the two alleles defined by a given SNP.
      AVAILABILITY AND IMPLEMENTATION: At http://kks.inf.kcl.ac.uk/MSbind.html the
      MSbind tool is available for calculating features of metastable conformations
      determined by putative miRNA binding sites.

PMID- 24292937
TI  - Exact likelihood computation in Boolean networks with probabilistic time delays,
      and its application in signal network reconstruction.
AB  - MOTIVATION: For biological pathways, it is common to measure a gene expression
      time series after various knockdowns of genes that are putatively involved in the
      process of interest. These interventional time-resolved data are most suitable
      for the elucidation of dynamic causal relationships in signaling networks. Even
      with this kind of data it is still a major and largely unsolved challenge to
      infer the topology and interaction logic of the underlying regulatory network.
      RESULTS: In this work, we present a novel model-based approach involving Boolean
      networks to reconstruct small to medium-sized regulatory networks. In particular,
      we solve the problem of exact likelihood computation in Boolean networks with
      probabilistic exponential time delays. Simulations demonstrate the high accuracy
      of our approach. We apply our method to data of Ivanova et al. (2006), where RNA
      interference knockdown experiments were used to build a network of the key
      regulatory genes governing mouse stem cell maintenance and differentiation. In
      contrast to previous analyses of that data set, our method can identify feedback
      loops and provides new insights into the interplay of some master regulators in
      embryonic stem cell development. AVAILABILITY AND IMPLEMENTATION: The algorithm
      is implemented in the statistical language R. Code and documentation are
      available at Bioinformatics online. CONTACT: duemcke@mpipz.mpg.de or
      tresch@mpipz.mpg.de SUPPLEMENTARY INFORMATION: Supplementary Materials are
      available at Bioinfomatics online.

PMID- 24292938
TI  - A mathematical model describing the mechanical kinetics of kinesin stepping.
AB  - MOTIVATION: Kinesin is a smart motor protein that steps processively forward and
      backward along microtubules (MTs). The mechanical kinetics of kinesin affecting
      its stepping behavior is not fully understood. Here, we propose a mathematical
      model to study the mechanical kinetics of forward and backward stepping of
      kinesin motor based on the four-state discrete stochastic model of the motor.
      RESULTS: Results show that the probabilities of forward and backward stepping can
      be modeled using the mean probabilities of forward and backward kinetic
      transitions, respectively. We show that the backward stepping of kinesin motor
      starts when the probability of adenosine diphosphate (ADP) binding to the motor
      is much higher than that of adenosine triphosphate (ATP) binding. Furthermore,
      our results indicate that the backward stepping is related to both ATP hydrolysis
      and synthesis with rate limiting factor being ATP synthesis. Low rate of ATP
      synthesis under high backward loads above 10 pN is also suggested as a reason for
      the detachment of kinesin motor from MT in the kinetic state MTcKinesincADPcPi.
      AVAILABILITY AND IMPLEMENTATION: The code for this work is written in Visual C#
      and is available by request from the authors.

PMID- 24292939
TI  - GPU linear and non-linear Poisson-Boltzmann solver module for DelPhi.
AB  - SUMMARY: In this work, we present a CUDA-based GPU implementation of a Poisson
      Boltzmann equation solver, in both the linear and non-linear versions, using
      double precision. A finite difference scheme is adopted and made suitable for the
      GPU architecture. The resulting code was interfaced with the electrostatics
      software for biomolecules DelPhi, which is widely used in the computational
      biology community. The algorithm has been implemented using CUDA and tested over
      a few representative cases of biological interest. Details of the implementation
      and performance test results are illustrated. A speedup of ~10 times was achieved
      both in the linear and non-linear cases. AVAILABILITY AND IMPLEMENTATION: The
      module is open-source and available at
      http://www.electrostaticszone.eu/index.php/downloads.

PMID- 24292940
TI  - Fingerprinting protein structures effectively and efficiently.
AB  - MOTIVATION: One common task in structural biology is to assess the similarities
      and differences among protein structures. A variety of structure alignment
      algorithms and programs has been designed and implemented for this purpose. A
      major drawback with existing structure alignment programs is that they require a
      large amount of computational time, rendering them infeasible for pairwise
      alignments on large collections of structures. To overcome this drawback, a
      fragment alphabet learned from known structures has been introduced. The method,
      however, considers local similarity only, and therefore occasionally assigns high
      scores to structures that are similar only in local fragments. METHOD: We propose
      a novel approach that eliminates false positives, through the comparison of both
      local and remote similarity, with little compromise in speed. Two kinds of
      contact libraries (ContactLib) are introduced to fingerprint protein structures
      effectively and efficiently. Each contact group of the contact library consists
      of one local or two remote fragments and is represented by a concise vector.
      These vectors are then indexed and used to calculate a new combined hit-rate
      score to identify similar protein structures effectively and efficiently.
      RESULTS: We tested our method on the high-quality protein structure subset of
      SCOP30 containing 3297 protein structures. For each protein structure of the
      subset, we retrieved its neighbor protein structures from the rest of the subset.
      The best area under the Receiver-Operating Characteristic curve, archived by
      ContactLib, is as high as 0.960. This is a significant improvement compared with
      0.747, the best result achieved by FragBag. We also demonstrated that
      incorporating remote contact information is critical to consistently retrieve
      accurate neighbor protein structures for all- query protein structures.
      AVAILABILITY AND IMPLEMENTATION: https://cs.uwaterloo.ca/~xfcui/contactlib/.

PMID- 24292941
TI  - AISAIC: a software suite for accurate identification of significant aberrations
      in cancers.
AB  - Accurate identification of significant aberrations in cancers (AISAIC) is a
      systematic effort to discover potential cancer-driving genes such as oncogenes
      and tumor suppressors. Two major confounding factors against this goal are the
      normal cell contamination and random background aberrations in tumor samples. We
      describe a Java AISAIC package that provides comprehensive analytic functions and
      graphic user interface for integrating two statistically principled in silico
      approaches to address the aforementioned challenges in DNA copy number analyses.
      In addition, the package provides a command-line interface for users with
      scripting and programming needs to incorporate or extend AISAIC to their
      customized analysis pipelines. This open-source multiplatform software offers
      several attractive features: (i) it implements a user friendly complete pipeline
      from processing raw data to reporting analytic results; (ii) it detects deletion
      types directly from copy number signals using a Bayes hypothesis test; (iii) it
      estimates the fraction of normal contamination for each sample; (iv) it produces
      unbiased null distribution of random background alterations by iterative
      aberration-exclusive permutations; and (v) it identifies significant consensus
      regions and the percentage of homozygous/hemizygous deletions across multiple
      samples. AISAIC also provides users with a parallel computing option to leverage
      ubiquitous multicore machines. AVAILABILITY AND IMPLEMENTATION:  AISAIC is
      available as a Java application, with a user's guide and source code, at
      https://code.google.com/p/aisaic/.

PMID- 24292942
TI  - Alignment does not influence cartilage T2 in asymptomatic knee joints.
AB  - PURPOSE: To investigate whether the static knee alignment affects articular
      cartilage ultrastructures when measured using T2 relaxation among asymptomatic
      subjects. METHODS: Both knee joints (n = 96) of 48 asymptomatic volunteers (26
      females, 22 males; 25.4 +/- 1.7 years; no history of major knee trauma or
      surgery) were evaluated clinically (Lysholm, Tegner) and by MRI (hip-knee-ankle
      angle, standard knee protocol, T2 mapping). Group (n = 4) division was as
      follows: neutral (<1 degrees  varus/valgus), mild varus (2 degrees -4 degrees 
      varus), severe varus (>4 degrees  varus) and valgus (2 degrees -4 degrees 
      valgus) deformity with n = 12 subjects/group; n = 24 knees/group. Regions of
      interest (ROI) for T2 assessment were placed within full-thickness cartilage
      across the whole joint surface and were divided respecting compartmental as well
      as functional joint anatomy. RESULTS: Leg alignment was 0.7 degrees  +/- 0.5
      degrees  varus among neutral, 3.0 degrees  +/- 0.6 degrees  varus among mild
      varus, 5.0 degrees  +/- 1.1 degrees  varus among severe varus and 2.5 degrees  +/
      0.7 degrees  valgus among valgus group subjects and thus significantly
      different. No differences between the groups emerged from clinical measures. No
      morphological pathology was detected in any knee joint. Global T2 values (42.3 +/
      2.3; 37.7-47.9 ms) of ROIs placed within every knee joint per subject were not
      different between alignment groups or between genders, respectively. CONCLUSION:
      Static frontal plane leg malalignment does not affect cartilage ultrastructure
      among young, asymptomatic individuals as measured by T2 quantitative imaging.
      LEVEL OF EVIDENCE: Cross-sectional study, Level II-III.

PMID- 24292943
TI  - Sagittal plane evaluation of patellofemoral movement in patellofemoral pain
      patients with no evidence of maltracking.
AB  - PURPOSE: The cause of abnormal patellar kinematics in patients with
      patellofemoral pain remains unclear. Many patients who develop patellofemoral
      pain symptoms do not exhibit evidence of maltracking. In these patients, sagittal
      plane evaluation of patellofemoral movement should be performed. METHODS: Knee
      radiographs were obtained for forty healthy volunteers and thirty patients at 0
      degrees , 30 degrees , 60 degrees , 90 degrees  and 120 degrees  of flexion in a
      standing weight-bearing position. The degree of active patellar movement was
      measured by a newly developed technique called "patellar motion angle". Three
      independent examiners sequentially performed all of the measurements under
      identical conditions. RESULTS: A significant decrease in the patellar motion
      angle was found during deep knee flexion from 90 degrees  to 120 degrees  in the
      patient group compared to the volunteer group (mean 18.5 degrees  +/- 5.8 degrees
      and 23.6 degrees  +/- 6.2 degrees , respectively) (P = 0.001). From 0 degrees 
      to 90 degrees  of knee flexion, no significant differences in the patellar motion
      angle were found between the two groups. CONCLUSION: Sagittal plane
      patellofemoral joint kinematics is an area of interest in the study of the
      mechanical factors associated with patellofemoral pain. This study demonstrated a
      decrease in patellar movement during deep knee bending activity in patients with
      patellofemoral pain. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 24292944
TI  - Identification of nucleolin as a lipid-raft-dependent beta1-integrin-interacting
      protein in A375 cell migration.
AB  - Lipid rafts are related to cell surface receptor function. Integrin is a major
      surface receptor protein in cell adhesion and migration on the extracellular
      matrix (ECM). Here, we showed that lipid rafts played a critical role in human
      melanoma A375 cell spreading and migration on fibronectin; an important component
      of the ECM that interacts with beta1 integrin. We found that the disruption of
      lipid rafts did not markedly inhibit the expression and activation of beta1
      integrin. By coimmunoprecipitation and mass spectrometry, we investigated the
      influence of lipid rafts on the beta1 integrin complex and identified nucleolin
      as a potential lipid-raft-dependent beta1-integrin-interacting protein. Upon
      confirmation of the interaction between beta1 integrin and nucleolin, further
      studies revealed that nucleolin colocalized with beta1 integrin in lipid rafts
      and raft disruption interrupted their association. In addition, knockdown of
      nucleolin markedly attenuated A375 cell spreading and migration on fibronectin.
      Taken together, we demonstrated that nucleolin is a critical lipid-raft-dependent
      beta1-integrin-interacting protein in A375 cell spreading and migration on
      fibronectin. 

PMID- 24292945
TI  - Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of
      ischemic brain damage in rats.
AB  - Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from
      the chemically related antipsychotic drug tiospirone, and it improves
      neurological functions of the ischemic brain and is effective in treatment of
      schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading
      candidate for neurological regenerative therapy because of their neural
      differentiation properties in damaged brain. We investigated whether the
      transplantation of neural progenitor cells (NPCs) derived from adipose
      mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects
      in an animal model of focal cerebral ischemia. In combination therapy groups,
      significant reduction of infarct volume and improvement of neurological functions
      were observed at 3 days after middle cerebral artery occlusion (MCAO) compared
      with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti
      apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs
      alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone
      and NPCs induced the expression of endogenous neurotrophic factor gene brain
      derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell
      derived neurotrophic factor (GDNF). The immunohistochemical investigation
      revealed that the ziprasidone and NPCs attenuated the increased intensity of
      microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of
      transplanted NPCs on day 7 with combination therapy was significantly higher than
      with NPCs alone. These effects might be responsible for improved functional
      behavior and increased survival of NPCs. Our finding indicates that combination
      therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain
      injury. 

PMID- 24292946
TI  - Structural and functional characterization of Arabidopsis GSK3-like kinase
      AtSK12.
AB  - Plant GSK3-like kinases are key regulators that modulate a broad range of
      physiological processes such as cell growth, stomatal and flower development,
      responses for abiotic and biotic stress, and carbohydrate metabolism. Arabidopsis
      Shaggy/GSK3-like kinases (AtSK) consist of ten members that are classified into
      four subfamilies (I~IV). Only one of these Arabidopsis GSK3s, BIN2 (also named
      AtSK21), has been characterized by biochemical and genetic studies. BIN2 acts as
      a negative regulator in brassinosteroid (BR) signaling that controls cell growth
      and differentiation. Recent studies suggest that at least seven AtSKs are
      involved in BR signaling. However, specificities for the substrates and the
      functional differences of each member of the family remain to be determined. Here
      we report structural characteristics and distinct function of AtSK12 compared
      with BIN2. AtSK12 has a longer N-terminal extension, which is absent in BIN2.
      Transgenic plants overexpressing the AtSK12 mutant carrying deletion of Nterminal
      region display more severe dwarf phenotypes than those of the wild-type AtSK12.
      Microscopic analysis reveals that N-terminal-deleted AtSK12 accumulates in the
      nucleus. This implies that structural difference in the Nterminal region of AtSK
      members contributes to their subcellular localization. In contrast to BIN2,
      overexpression of AtSK12 does not cause a stomatal cluster. Furthermore, we show
      that YODA MAPKKK, which controls stomatal development, interacts with BIN2 but
      not with AtSK12. Our results suggest that AtSK12 mediates BR-regulated cell
      growth but not stomatal development while BIN2 regulates both processes. Our
      study provides evidence that different GSK3 members can have overlapping but non
      identical functions. 

PMID- 24292947
TI  - ELOVL2 gene polymorphisms are associated with increases in plasma
      eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement.
AB  - Fish oil supplementation provides an inconsistent degree of protection from
      cardiovascular disease (CVD), which may be attributed to genetic variation.
      Single nucleotide polymorphisms (SNPs) in the elongation-of-very-long-chain-fatty
      acids-2 (ELOVL2) gene have been strongly associated with plasma proportions of n
      3 long-chain polyunsaturated fatty acids (LC-PUFA). We investigated the effect of
      genotype interaction with fish oil dosage on plasma n-3 LC-PUFA proportions in a
      parallel double-blind controlled trial, involving 367 subjects randomised to
      treatment with 0.45, 0.9 and 1.8 g/day eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) (1.51:1) or olive oil placebo for 6 months. We
      genotyped 310 subjects for ELOVL2 gene SNPs rs3734398, rs2236212 and rs953413. At
      baseline, carriers of all minor alleles had lower proportions of plasma DHA than
      non-carriers (P = 0.021-0.030). Interaction between genotype and treatment was a
      significant determinant of plasma EPA (P < 0.0001) and DHA (P = 0.004-0.032).
      After the 1.8 g/day dose, carriers of ELOVL2 SNP minor alleles had approximately
      30 % higher proportions of EPA (P = 0.002-0.004) and 9 % higher DHA (P = 0.013
      0.017) than non-carriers. Minor allele carriers could therefore particularly
      benefit from a high intake of EPA and DHA in maintaining high levels of plasma n
      3 PUFA conducive to protection from CVD. 

PMID- 24292948
TI  - Expression of "brown-in-white" adipocyte biomarkers shows gender differences and
      the influence of early dietary exposure.
AB  - Induction of brown-like adipocytes (brite) in white adipose tissues may allow the
      conversion of lipid storage cells in fat-burning cells. Little is known
      concerning browning potential in males compared with females. In this study, we
      aimed to analyse whether gender differences were present in gene expression of
      "brite" markers as well as the impact of dietary manipulation at both early
      stages and adulthood in rats. We have determined the expression of brite markers
      and genes associated with lipid and energy metabolism in inguinal adipose tissue
      in adult male and female rats. We have analysed the impact of high-fat (HF) diet
      in adult life and of early leucine supplementation (2 %) during lactation.
      Results show that although both genders have the potential to induce brite genes
      in inguinal adipose tissue, males expressed higher levels (CIDEA, HOXC9 and
      SHOX2), which would imply a higher browning capacity in comparison with females.
      Minor impact of HF diet in adult life was observed in most of the genes studied.
      Interestingly, results showed that early Leu was able to compromise the metabolic
      fate of white and brite adipocytes later in adult life. Leucine supplementation
      programmed higher expression of cell death-inducing DFFA-like effector,
      accompanied with induction of sterol regulatory element binding transcription 1c
      factor and lower UPC2 expression, particularly in females. In addition, Leucine
      supplementation was associated with higher expression of leptin and PPARgamma and
      decreased carnitine palmitoyl transferase in both genders. Although the exact
      role of these adaptations needs further comprehensive analysis, dietary Leu
      supplementation at early age programmed inguinal adipose tissue in a gender
      specific manner. 

PMID- 24292949
TI  - Dietary supplementation with soy isoflavones or replacement with soy proteins
      prevents hepatic lipid droplet accumulation and alters expression of genes
      involved in lipid metabolism in rats.
AB  - Accumulation of hepatic lipid droplet (HLD) is the hallmark pathology of non
      alcoholic fatty liver disease (NAFLD). This study examined the effects of soy
      isoflavones (ISF) and different amounts of soy proteins on the accumulation of
      HLD, lipid metabolism and related gene expression in rats. Weanling Sprague
      Dawley rats were fed diets containing either 20 % casein protein without (D1) or
      with (D2) supplemental ISF (50 mg/kg diet) or substitution of casein with
      increasing amounts of alcohol-washed soy protein isolate (SPI, 5, 10, and 20 %;
      D3, D4, D5) for 90 days. Dietary casein (20 %) induced accumulation of HLD in
      female, but not in male rats. Both soy proteins and ISF remarkably prevented the
      formation of HLD. Soy proteins lowered hepatic total cholesterol and triglyceride
      in a dose-dependent manner. Interestingly, soy proteins but not ISF significantly
      increased free fatty acids in the liver of the female rats compared to D1.
      Proteomic analysis showed that at least 3 enzymes involved in lipogenesis were
      down-regulated and 7 proteins related to fatty acid beta-oxidation or lipolysis
      were up-regulated by soy protein over D1. Additionally, 9 differentially
      expressed proteins identified were related to amino acid metabolism, 5 to
      glycolysis and 2 to cholesterol metabolism. Dietary ISF and SPI markedly reduced
      hepatic-peroxisome-proliferator-activated receptor gamma2 (PPARgamma2) and fat
      specific protein 27 (FSP27) in female rats. Overall, this study has shown that
      partial or full replacement of dietary casein by soy protein or supplementation
      with soy ISF can effectively prevent the accumulation of HLD. The potential
      molecular mechanism(s) involved might be due to suppression of lipogenesis and
      stimulation of lipolysis and down-regulation of PPARgamma2 and FSP27. This
      suggests that consumption of soy foods or supplements might be a useful strategy
      for the prevention or treatment of fatty liver diseases. 

PMID- 24292950
TI  - Evaluation of genotoxic effects of benzene and its derivatives in workers of gas
      stations.
AB  - The search for reliable biomarkers of human exposure to benzene and its
      derivatives is still subject of research. Many of the proposed biomarkers have
      limitations ranging from the low sensitivity to the wide variability of results.
      Thus, the aim of our study was to assess the frequencies of chromosomal
      abnormalities (CA) and sister chromatid exchanges (SCE) in workers of gas
      stations, with (cases, n = 19) and without (local controls, n = 6) risk of
      exposure to benzene and its derivatives, comparing them with the results from the
      general population (external controls, n = 38). The blood dosages of benzene,
      toluene, and xylenes were measured in all participants. Blood solvent levels were
      compared with the findings obtained in cytogenetic evaluation and a research
      protocol which included data of the workplace, lifestyle, and health of the
      individuals. We did not detect the presence of benzene and its derivatives and
      did not find chromosomal damage that may be associated with the gas station
      activity in cases. Moreover, although we found an association of increased SCE
      and the working time in the local controls, the values found for SCE are within
      normal limits. Thus, our evaluation of SCE and CA reflected the levels of benzene
      and its derivatives observed in the blood. We believe, therefore, that SCE and CA
      may actually constitute possible tests for the evaluation of these exposures.
      However, we believe that further studies, including individuals at risk, are
      important to confirm this assertion.

PMID- 24292951
TI  - Assessment of trace elements in the shell layers and soft tissues of the pearl
      oyster Pinctada radiata using multivariate analyses: a potential proxy for
      temporal and spatial variations of trace elements.
AB  - Concentrations of trace elements (Cd, Cu, Ni, Pb, V, and Zn) were determined in
      the soft tissues (adductor muscle and gills) of the pearl oyster Pinctada radiata
      and surficial sediments from two sampling sites located in the northern part of
      the Persian Gulf by Graphite Furnace Atomic Absorption Spectrophotometer (GFAAS).
      Moreover, the levels of Li, Mg, Al, Mn, Fe, Cu, Sr, Ba, Pb, and Zn were measured
      in two shell layers (prismatic and nacreous) using Laser Ablation Inductively
      Coupled Plasma Mass Spectrometer (LA-ICP-MS). There were significant differences
      between the sampling sites with regard to mean concentrations of Cu, Mn, and Al
      in the prismatic layers of the shells. But in terms of the soft tissues, only in
      the case of Ni accumulation in the muscle significant differences between the
      sites could be observed. No significant differences could be found between the
      sites from the elements concentrations in the sediments point of view. The levels
      of Cd, Cu, Ni, and Zn in the gills were markedly higher than those in the muscle.
      Concentrations of Mn, Mg, Li, and Cu in the prismatic layer were significantly
      higher than in the nacreous but the reverse case could be found for Sr. The
      patterns of metal occurrence in the selected tissues, shell layers, and sediments
      exhibited the following descending order: Zn, Ni > Cd, Cu > V, and Pb and Zn, Ni,
      Cd > Cu, V, and Pb for muscle and gills, respectively; Zn > Cu, Ni, Pb, Cd, and V
      for sediments; Mg > Sr, Mn, Li, Al, Fe, Ba, Cu, Pb, and Zn for the prismatic
      layer; and Sr, Mg > Mn, Al, Fe, Li, Ba, Cu, Pb, and Zn for the nacreous layer. In
      most cases, the temporal variations of the elements levels in the prismatic layer
      were clearer than those in the nacreous layer (especially for Li, Mg, Mn, Pb, and
      Fe). Comparison of the gained data from this study with the other relevant
      researches shows that in most cases the levels of the elements in this
      investigation either fell within the range for other world areas or were lower.
      Generally, it can be concluded that the shell (especially prismatic layer) of P.
      radiata can be considered as a suitable proxy for temporal and spatial variations
      of the trace elements (and probably some environmental parameters) in the study
      area.

PMID- 24292952
TI  - EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction
      apoptosis and angiogenesis.
AB  - This study aimed to analyze the expression, clinical significance of epithelial
      membrane protein-1 (EMP1) in nasopharyngeal carcinoma, and the biological effect
      in its cell line by EMP1 overexpression. Immunohistochemistry and Western blot
      were used to analyze the EMP1 protein expression in 75 cases of nasopharyngeal
      cancer and 31 cases of normal tissues to study the relationship between EMP1
      expression and clinical factors. Recombinant lentiviral vector was constructed to
      overexpress EMP1 and then infect nasopharyngeal cancer CNE2 cell line.
      Quantitative real-time RT-PCR and Western blot were used to detect the mRNA level
      and protein of EMP1. MTT assay, cell apoptosis, migration, and invasion assays
      were also conducted to determine the influence of the upregulated expression of
      EMP1 that might be found on CNE2 cells' biological effect. Immunohistochemistry
      and Western blot: The level of EMP1 protein expression was found to be
      significantly lower in nasopharyngeal cancer tissue than in the normal tissues (P
      < 0.05). Decreased expression of EMP1 was significantly correlated with T stages,
      lymph node metastasis, clinic stage, and histological grade of patients with
      nasopharyngeal cancer (P < 0.05). Meanwhile, the loss of EMP1 expression
      correlated significantly with poor overall survival time by Kaplan-Meier analysis
      (P < 0.05). The result of biological function has shown that CNE2 cell
      transfected EMP1 had a lower survival fraction, higher cell apoptosis,
      significant decrease in migration and invasion, higher caspase-9, and lower
      vascular endothelial growth factor C protein expression compared with CNE2 cell
      untransfected EMP1 (P < 0.05). EMP1 expression decreased in nasopharyngeal cancer
      and correlated significantly T stages, lymph node metastasis, clinic stage,
      histological grade, and poor overall survival, suggesting that EMP1 may play
      important roles as a negative regulator to nasopharyngeal cancer cell.

PMID- 24292954
TI  - Dextran-functionalized magnetic fluid mediating magnetohyperthermia for treatment
      of Ehrlich-solid-tumor-bearing mice: toxicological and histopathological
      evaluations.
AB  - Dextran-functionalized maghemite fluid (DexMF) has been tested to treat Ehrlich
      solid-tumor-bearing mice, evidencing its potential use in mediating
      magnetohyperthermia in breast cancer treatment. However, although magnetic
      nanoparticles tend to accumulate in tumor tissues, part of the nanomaterial can
      reach the blood stream, and then the organism. The aim of this study was to
      investigate the acute systemic effects of the intratumoral injection of DexMF
      mediating magnetohyperthermia in the treatment of an advanced clinical Ehrlich
      solid-tumor, assessed through histopathological analyses of liver, kidneys, heart
      and spleen, comet assay, micronucleus test, hemogram, and serum levels of
      bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl
      transferase, alkaline phosphatase, creatinine, and urea. The tumor's
      histopathology and morphometry were used to assess its aggressiveness and
      regression. DexMF mediating hyperthermia was effective in containing tumor
      aggressiveness and in inducing tumor regression, besides showing no toxic
      effects. Its physical characteristics also suggest that it is safe to use in
      other biomedical applications. 

PMID- 24292955
TI  - A vinyl chloride-exposed worker with an adrenal gland angiosarcoma: a case
      report.
AB  - Adrenal epithelioidangiosarcoma (AEA) is a rare neoplasm that accounts for less
      than 1% of sarcomas. Due to its rarity, it can easily be misdiagnosed, both by
      the clinician and the pathologist. Data on the patient's occupational history was
      collected and analyzed. The bibliographic data was found on the PUBMED
      bibliographic search site after entering the word "extrahepaticangiosarcoma". We
      report a case of adrenal epithelioidangiosarcoma (AEA) in a 68 yr-old Caucasian
      male factory worker exposed to Vinyl Chloride (VC) for 15 yr. He underwent
      surgery, chemotherapy and radiotherapy. Hepatic angiosarcoma is a known
      consequence of VC exposure, but occupational causality of extra-hepatic
      angiosarcoma is controversial. Extra-hepatic angiosarcomas have been reported in
      VC workers, but never AEA. Cancerogenic effects of VC involve all endothelial
      areas of the body and extra-hepatic endothelial tumors may also be caused by this
      substance. This is the first published report of AEA diagnosed in a worker
      exposed to VC.

PMID- 24292956
TI  - The potential utility of geminin as a predictive biomarker in breast cancer.
AB  - Compared with other markers of cell proliferation, geminin is unique being
      expressed selectively during the proliferative phase of the cell cycle,
      specifically S, G2 and early mitosis, disappearing completely at the metaphase
      anaphase transition. We aimed to compare the prognostic significance of geminin
      to that of Ki67, a proliferation marker which has been investigated in many
      breast cancer studies. Breast cancer tissue microarrays containing 368 tumours
      were stained using anti-geminin and Ki67 antibodies. Labelling index (LI) was
      calculated for geminin, and the percentage of positive cancer nuclei was
      determined for Ki67. A receiver operation characteristics analysis was used to
      determine the optimum cut-off value for geminin (LI >= 2), and for Ki67, a score
      of >=14 % was considered as positive for survival analysis. Geminin expression
      correlated positively with Ki67 expression (r = 0.686, p = 0.001). Survival
      analysis showed only geminin, and not Ki67-positive patients to have poor (breast
      cancer-specific survival) BCSS [HR 2.85 (1.53-5.32)] and (disease-free survival)
      DFS [HR 2.63 (1.47-4.71)]. On univariate analysis, along with known
      clinicopathological variables, both Ki67 and geminin LI were found to be
      significant predictors of BCSS and DFS. On multivariate analysis, only tumour
      size, nodal status and adjuvant hormonal therapy were found to be independent
      predictors for both BCSS and DFS, while geminin positivity (LI >= 2 %) was found
      to be an independent predictor for BCSS [HR 2.27 (1.01-5.06); p = 0.04]. In
      comparison with Ki67, a more established proliferation marker, geminin expression
      was a better predictor of adverse outcome in this cohort of breast cancers.
      Selective expression of geminin during the proliferative phase of the cell cycle
      and its nuclear specificity increase its potential to be used as an alternative
      marker of proliferation in breast cancer patients. 

PMID- 24292957
TI  - Phosphorylated VEGFR2 and hypertension: potential biomarkers to indicate VEGF
      dependency of advanced breast cancer in anti-angiogenic therapy.
AB  - The efficacy of anti-VEGF agents probably lies on VEGF-dependency. Apatinib, a
      specific tyrosine kinase inhibitor that targets VEGF receptor 2, was assessed in
      patients with advanced breast cancer (ABC) (ClinicalTrials.gov NCT01176669 and
      NCT01653561). This substudy was to explore the potential biomarkers for VEGF
      dependency in apatinib-treated breast cancer. Eighty pretreated patients received
      apatinib 750 or 500 mg/day orally in 4-week cycles. Circulating biomarkers were
      measured using a multiplex assay, and tissue biomarkers were identified with
      immunostaining. Baseline characteristics and adverse events (AEs) were included
      in the analysis. Statistical confirmation of independent predictive factors for
      anti-tumor efficacy was performed using Cox and Logistic regression models.
      Median progression-free survival (PFS) was 3.8 months, and overall survival (OS)
      was 10.6 months, with 17.5 % of objective response rate. Prominent AEs (>=60 %)
      were hypertension, hand-foot skin reaction (HFSR), and proteinuria. Higher tumor
      phosphorylated VEGFR2 (p-VEGFR2) expressions (P = 0.001), higher baseline serum
      soluble VEGFR2 (P = 0.031), hypertension (P = 0.011), and HFSR (P = 0.018) were
      significantly related to longer PFS, whereas hypertension (P = 0.002) and HFSR (P
      = 0.001) were also related to OS. Based on multivariate analysis, only p-VEGFR2
      (adjusted HR, 0.40; P = 0.013) and hypertension (adjusted HR, 0.58; P = 0.038)
      were independent predictive factors for both PFS and clinical benefit rate.
      Apatinib had substantial antitumor activity in ABC and manageable toxicity. p
      VEGFR2 and hypertension may be surrogate predictors of VEGF-dependency of breast
      cancer, which may identify an anti-angiogenesis sensitive population. 

PMID- 24292958
TI  - Biomarkers for NeuroAIDS: recent progress in the field.

PMID- 24292959
TI  - Wellness and health omics linked to the environment: the WHOLE approach to
      personalized medicine.
AB  - The WHOLE approach to personalized medicine represents an effort to integrate
      clinical and genomic profiling jointly into preventative health care and the
      promotion of wellness. Our premise is that genotypes alone are insufficient to
      predict health outcomes, since they fail to account for individualized responses
      to the environment and life history. Instead, integrative genomic approaches
      incorporating whole genome sequences and transcriptome and epigenome profiles,
      all combined with extensive clinical data obtained at annual health evaluations,
      have the potential to provide more informative wellness classification. As with
      traditional medicine where the physician interprets subclinical signs in light of
      the person's health history, truly personalized medicine will be founded on
      algorithms that extract relevant information from genomes but will also require
      interpretation in light of the triggers, behaviors, and environment that are
      unique to each person. This chapter discusses some of the major obstacles to
      implementation, from development of risk scores through integration of diverse
      omic data types to presentation of results in a format that fosters development
      of personal health action plans. 

PMID- 24292960
TI  - Characterizing multi-omic data in systems biology.
AB  - In today's biology, studies have shifted to analyzing systems over discrete
      biochemical reactions and pathways. These studies depend on combining the results
      from scores of experimental methods that analyze DNA; mRNA; noncoding RNAs, DNA,
      RNA, and protein interactions; and the nucleotide modifications that form the
      epigenome into global datasets that represent a diverse array of "omics" data
      (transcriptional, epigenetic, proteomic, metabolomic). The methods used to
      collect these data consist of high-throughput data generation platforms that
      include high-content screening, imaging, flow cytometry, mass spectrometry, and
      nucleic acid sequencing. Of these, the next-generation DNA sequencing platforms
      predominate because they provide an inexpensive and scalable way to quickly
      interrogate the molecular changes at the genetic, epigenetic, and transcriptional
      level. Furthermore, existing and developing single-molecule sequencing platforms
      will likely make direct RNA and protein measurements possible, thus increasing
      the specificity of current assays and making it possible to better characterize
      "epi-alterations" that occur in the epigenome and epitranscriptome. These diverse
      data types present us with the largest challenge: how do we develop software
      systems and algorithms that can integrate these datasets and begin to support a
      more democratic model where individuals can capture and track their own medical
      information through biometric devices and personal genome sequencing? Such
      systems will need to provide the necessary user interactions to work with the
      trillions of data points needed to make scientific discoveries. Here, we describe
      novel approaches in the genesis and processing of such data, models to integrate
      these data, and the increasing ubiquity of self-reporting and self-measured
      genomics and health data. 

PMID- 24292961
TI  - High-throughput translational medicine: challenges and solutions.
AB  - Recent technological advances in genomics now allow producing biological data at
      unprecedented tera- and petabyte scales. Yet, the extraction of useful knowledge
      from this voluminous data presents a significant challenge to a scientific
      community. Efficient mining of vast and complex data sets for the needs of
      biomedical research critically depends on seamless integration of clinical,
      genomic, and experimental information with prior knowledge about genotype
      phenotype relationships accumulated in a plethora of publicly available
      databases. Furthermore, such experimental data should be accessible to a variety
      of algorithms and analytical pipelines that drive computational analysis and data
      mining. Translational projects require sophisticated approaches that coordinate
      and perform various analytical steps involved in the extraction of useful
      knowledge from accumulated clinical and experimental data in an orderly
      semiautomated manner. It presents a number of challenges such as (1) high
      throughput data management involving data transfer, data storage, and access
      control; (2) scalable computational infrastructure; and (3) analysis of large
      scale multidimensional data for the extraction of actionable knowledge.We present
      a scalable computational platform based on crosscutting requirements from
      multiple scientific groups for data integration, management, and analysis. The
      goal of this integrated platform is to address the challenges and to support the
      end-to-end analytical needs of various translational projects. 

PMID- 24292962
TI  - Computational approaches for human disease gene prediction and ranking.
AB  - While candidate gene association studies continue to be the most practical and
      frequently employed approach in disease gene investigation for complex disorders,
      selecting suitable genes to test is a challenge. There are several computational
      approaches available for selecting and prioritizing disease candidate genes. A
      majority of these tools are based on guilt-by-association principle where novel
      disease candidate genes are identified and prioritized based on either functional
      or topological similarity to known disease genes. In this chapter we review the
      prioritization criteria and the algorithms along with some use cases that
      demonstrate how these tools can be used for identifying and ranking human disease
      candidate genes. 

PMID- 24292963
TI  - A personalized treatment for lung cancer: molecular pathways, targeted therapies,
      and genomic characterization.
AB  - Lung cancer is a heterogeneous, complex, and challenging disease to treat. With
      the arrival of genotyping and genomic profiling, our simple binary division of
      lung cancer into non-small-cell lung cancer (NSCLC) and small-cell lung cancer
      (SCLC) is no longer acceptable. In the past decade and with the advent of
      personalized medicine, multiple advances have been made in understanding the
      underlying biology and molecular mechanisms of lung cancer. Lung cancer is no
      longer considered a single disease entity and is now being subdivided into
      molecular subtypes with dedicated targeted and chemotherapeutic strategies. The
      concept of using information from a patient's tumor to make therapeutic and
      treatment decisions has revolutionized the landscape for cancer care and research
      in general.Management of non-small-cell lung cancer, in particular, has seen
      several of these advances, with the understanding of activating mutations in
      EGFR, fusion genes involving ALK, rearrangements in ROS-1, and ongoing research
      in targeted therapies for K-RAS and MET. The next era of personalized treatment
      for lung cancer will involve a comprehensive genomic characterization of
      adenocarcinoma, squamous-cell carcinoma, and small-cell carcinoma into various
      subtypes. Future directions will involve incorporation of molecular
      characteristics and next generation sequencing into screening strategies to
      improve early detection, while also having applications for joint treatment
      decision making in the clinics with patients and practitioners. Personalization
      of therapy will involve close collaboration between the laboratory and the
      clinic. Given the heterogeneity and complexity of lung cancer treatment with
      respect to histology, tumor stage, and genomic characterization, mind mapping has
      been developed as one of many tools which can assist physicians in this era of
      personalized medicine. We attempt to utilize the above tool throughout this
      chapter, while reviewing lung cancer epidemiology, lung cancer treatment, and the
      genomic characterization of lung cancer. 

PMID- 24292964
TI  - Rejection and victimization among elementary school children: the buffering role
      of classroom-level predictors.
AB  - This study examined features of classroom peer ecologies and teaching practices
      that may attenuate the prevalence of victimization and its connection to peer
      rejection. Participants were 1020 elementary school students from 54 classrooms
      and their teachers followed for one academic year. In the majority of classrooms
      students who were rejected in fall tended to be victimized in spring, but the
      strength of this association varied across classrooms. The positive relationship
      between rejection in the fall and victimization in the spring was stronger in
      classrooms where victimization was strongly centralized around specific victims
      in the fall. In addition, victimization in the spring was higher in classrooms
      that had higher levels of peer rejection in the fall, where victimization was
      strongly centralized in the fall, and where teachers reported making fewer
      efforts to reduce social status inequality. This study contributes to a growing
      body of research into contextual factors that may attenuate negative outcomes
      associated with peer rejection and reduce levels of peer harassment in elementary
      school. 

PMID- 24292966
TI  - A tripeptide (NSK) inhibits Japanese encephalitis virus infection in vitro and in
      vivo.
AB  - Japanese encephalitis virus (JEV) is a major pathogen that can cause acute viral
      encephalitis in both humans and animals. Domain III of the viral envelope protein
      (EDIII) is involved in binding to host cell receptor(s) to facilitate virus
      entry. Our previous study showed that the loop3 peptide of EDIII possesses
      antiviral activity against JEV infection. In this paper, we demonstrate that
      three residues (NSK) in loop3 are responsible for the antiviral activity of loop3
      peptide. In vitro experiments showed that the tripeptide NSK could inhibit JEV
      infection in both BHK-21 and Neuro-2A cells by inhibiting attachment of JEV to
      the cells, with IC50 values of 8 MUM and 6.5 MUM, respectively. In vivo
      experiments showed that the tripeptide could increase the survival of mice
      challenged with JEV to 75 % when administrated intracerebrally. Therefore, this
      tripeptide may serve as the basis for the development of novel antiviral agents
      against Japanese encephalitis virus infection.

PMID- 24292965
TI  - Cognitive vulnerabilities as mediators between emotional abuse and depressive
      symptoms.
AB  - This study tested whether childhood parental emotional abuse and peer emotional
      bullying serve as antecedents of depression in adolescence and identified the
      cognitive mechanisms involved in this process. It was hypothesized that the
      experience of emotional abuse would predict depressive symptoms via development
      of rumination and negative inferences. A 3-wave longitudinal study was carried
      out with 998 adolescents (471 girls and 526 boys) between 13 and 17 years of age.
      Results showed that emotional abuse by parents and peers at Time 1 predicted a
      worsening of several cognitive vulnerabilities at Time 2. In addition, brooding
      mediated between the experiences of abuse and the increase of depressive symptoms
      at Time 3. Thus, findings suggest that the experiences of childhood emotional
      abuse by parents and peers serve as antecedents to develop a negative cognitive
      style, vulnerability that, once developed, is a risk factor for the onset of
      depressive symptoms in adolescence. 

PMID- 24292967
TI  - Phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) field strains in
      central China based on the ORF3 gene and the main neutralization epitopes.
AB  - Since 2010, porcine epidemic diarrhea has re-emerged with devastating impact on
      the swine-raising industry in central China. To investigate the epidemic
      characteristics of PEDV, the complete ORF3 genes of 14 PEDV field strains from
      central China during 2012 to 2013 were cloned, sequenced and compared with
      reference strains. Phylogenetic analysis based on the complete ORF3 gene showed
      that the PEDVs in central China and the reference strains could be divided into
      three groups: G1, G2, and G3. The 14 PEDV isolates were classified as G1 and
      showed a close relationship to some Chinese strains isolated previously in
      central China and differed genetically from recent isolates from southern China,
      Korean strains (SM98 and DB1865, 2012), the Chinese LZC strain (2007), and the
      vaccine strain (CV777) being used in China. Our findings suggested that the PEDVs
      circulating between 2012 and 2013 in central China might have evolved from
      earlier strains in the local region. To determine the reason for recent
      vaccination failures, we also studied variations in antigenicity of field strains
      by analyzing the three neutralizing epitope regions in the S gene. The results
      showed that the neutralizing epitopes at aa 245-252 were highly conserved, but
      most of the amino acid changes occurred in the epitope regions aa 7-146 and 271
      278. We speculate that the amino acid mutations in the neutralizing epitope
      regions may be associated with changes in the antigenicity of PEDV and
      consequently result in vaccination failure. Together, these findings may be
      useful for understanding the epidemiology of PEDV and may be relevant for
      designing of new and more efficacious vaccines. 

PMID- 24292968
TI  - Inpatient hypoglycemia: a challenge that must be addressed.
AB  - Hypoglycemia in the inpatient setting is a common occurrence with potentially
      harmful outcomes. Large trials in both the inpatient and outpatient settings have
      found a correlation between hypoglycemia and morbidity and mortality. The
      incidence of hypoglycemia is difficult to assess, due to a lack of standardized
      definitions and different methods of data collection between hospital systems.
      Risk factors that predispose to hypoglycemia involve the changing clinical
      statuses of patients, nutrition issues, and hospital processes. Mechanisms
      contributing to morbidity due to hypoglycemia may include an increase in
      sympathoadrenal responses, as well as indirect changes affecting cytokine
      production, coagulation, fibrinolysis, and endothelial function. Prevention of
      hypoglycemia requires implementation of several strategies that include patient
      safety, quality control, multidisciplinary communication, and transitions of
      care. In this article, we discuss all of these issues and provide suggestions to
      help predict and prevent hypoglycemic episodes during an inpatient stay. We
      address the issues that occur upon admission, during the hospital stay, and
      around the time of discharge. We believe that decreasing the incidence of
      inpatient hypoglycemia will both decrease costs and improve patient outcomes.

PMID- 24292969
TI  - Maternal and in utero determinants of type 2 diabetes risk in the young.
AB  - The global prevalence of diabetes mellitus has reached epidemic proportions. In
      2010, it was estimated that 6.4 % of the adult population (285 million) have
      diabetes. In recent years, the incidence of type 2 diabetes (T2D), a condition
      traditionally associated with aging, has been steadily increasing among younger
      individuals. It is now a well-established notion that the early-life period is a
      critical window of development and that influences during this period can
      "developmentally prime" the metabolic status of the adult. This review discusses
      the role of maternal and in utero influences on the developmental priming of T2D
      risk. Both human epidemiological studies and experimental animal models are
      beginning to demonstrate that early dietary challenges can accelerate the onset
      of age-associated metabolic disturbances, including insulin resistance, T2D,
      obesity, hypertension, and cardiovascular disease. These findings show that poor
      maternal nutrition can prime a prediabetes phenotype, often manifest as insulin
      resistance, by very early stages of life. Thus, the maternal diet is a critical
      determinant of premature T2D risk. While the mechanisms that link early nutrition
      to age-associated metabolic decline are currently unclear, preliminary findings
      suggest perturbations in a number of processes involved in cellular aging, such
      as changes in longevity-associated Sirtuin activity, epigenetic regulation of key
      metabolic genes, and mitochondrial dysfunction. Preliminary studies show that
      pharmacological interventions in utero and dietary supplementation in early
      postnatal life may alleviate insulin resistance and reduce T2D risk. However,
      further studies are warranted to fully understand the relationship between the
      early environment and long-term effects on metabolism. Such mechanistic insights
      will facilitate strategic interventions that prevent accelerated metabolic
      decline and the premature onset of T2D in the current and future generations.

PMID- 24292970
TI  - Glucose control during labor and delivery.
AB  - Neonatal hypoglycemia is an important consequence for the infant of the mother
      with diabetes. We have reviewed 24 published papers of various protocols for
      control of glucose in pregnant diabetic women during labor and delivery including
      our own published work. A relationship of maternal glucose during labor and
      neonatal hypoglycemia was sought in 19 of these studies. A significant inverse
      relationship was found in 10 reports with 3 others showing a similar trend. In
      all but 1 of these 13 studies the participants had pregestational diabetes. Three
      of the 6 studies not reporting an inverse relationship involved women with GDM.
      From this review it appears that the maternal glucose should be maintained
      between 4.0 and 6.0-7.0 mmol/L during labor. Most women with gestational
      diabetes, especially if they require <1.0 units/kg/d of insulin, can simply be
      monitored without intravenous insulin. Our own results demonstrate that a target
      glucose of 4.0-6.0 mmol/L can be used safely and results in a low rate of
      neonatal hypoglycemia using an iterative glucose insulin infusion protocol for
      women with pregestational diabetes and when needed for women with gestational
      diabetes.

PMID- 24292972
TI  - Making use of guava seed (Psidium guajava L): the effects of pre-treatments on
      its chemical composition.
AB  - The guava processing industry in Malaysia produces by-products in the form of
      seed core and peel. These by-products can be regarded as underused resources but
      there are concerns about their composition that prevent their use in the food and
      feed industries. This study aims to analyze the respective effects of heat
      treatments (boiling or autoclaving) and germination periods on the nutritional
      composition and phytochemical content of guava seeds. The guava seeds were found
      to contain 618, 78, 72, and 5 mg/g dry weight total dietary fiber, fat, protein,
      and ash, respectively. The tannin and saponin contents, but not the phytic acid
      content, were below the respective anti-nutritional thresholds. The heat
      treatments did not affect the total dietary fiber and ash contents but reduced
      all other chemical components to different extents (15-91%). Boiling did not
      reduce the phytic acid content substantially but autoclaving caused a reduction
      of 91% to a level below the anti-nutritional threshold. Germination for 14 days
      caused a significant reduction in nutrient contents in the range of 16-79%.
      Germination also reduced the phytic acid content by 90% in the seed but did not
      significantly affect the saponin content. Thus, guava seed can be treated
      thermally or germinated to manipulate its chemical composition to enable its use
      in the food and feed industries.

PMID- 24292971
TI  - Advanced glycation end products (AGE) and diabetes: cause, effect, or both?
AB  - Despite new and effective drug therapies, insulin resistance (IR), type 2
      diabetes mellitus (T2D) and its complications remain major medical challenges. It
      is accepted that IR, often associated with over-nutrition and obesity, results
      from chronically elevated oxidant stress (OS) and chronic inflammation. Less
      acknowledged is that a major cause for this inflammation is excessive consumption
      of advanced glycation end products (AGEs) with the standard western diet. AGEs,
      which were largely thought as oxidative derivatives resulting from diabetic
      hyperglycemia, are increasingly seen as a potential risk for islet beta-cell
      injury, peripheral IR and diabetes. Here we discuss the relationships between
      exogenous AGEs, chronic inflammation, IR, and T2D. We propose that under chronic
      exogenous oxidant AGE pressure the depletion of innate defense mechanisms is an
      important factor, which raises susceptibility to inflammation, IR, T2D and its
      complications. Finally we review evidence on dietary AGE restriction as a
      nonpharmacologic intervention, which effectively lowers AGEs, restores innate
      defenses and improves IR, thus, offering new perspectives on diabetes etiology
      and therapy.

PMID- 24292973
TI  - Directed evolution of GH43 beta-xylosidase XylBH43 thermal stability and L186
      saturation mutagenesis.
AB  - Directed evolution of beta-xylosidase XylBH43 using a single round of gene
      shuffling identified three mutations, R45K, M69P, and L186Y, that affect thermal
      stability parameter K(t)0.5 by -1.8 +/- 0.1, 1.7 +/- 0.3, and 3.2 +/- 0.4 
      degrees C, respectively. In addition, a cluster of four mutations near hairpin
      loop-D83 improved K(t)0.5 by ~3  degrees C; none of the individual amino acid
      changes measurably affect K(t)0.5. Saturation mutagenesis of L186 identified the
      variant L186K as having the most improved K(t)0.5 value, by 8.1 +/- 0.3  degrees
      C. The L186Y mutation was found to be additive, resulting in K(t)0.5 increasing
      by up to 8.8 +/- 0.3  degrees C when several beneficial mutations were combined.
      While k cat of xylobiose and 4-nitrophenyl-beta-D-xylopyranoside were found to be
      depressed from 8 to 83 % in the thermally improved mutants, K(m), K(ss)
      (substrate inhibition), and K(i) (product inhibition) values generally increased,
      resulting in lessened substrate and xylose inhibition.

PMID- 24292974
TI  - Functional consequences of chronic bladder ischemia.
AB  - The pathophysiology of lower urinary tract symptoms (LUTS), particularly in the
      elderly, seems to be multifactorial. One of the factors involved may be chronic
      ischemia of the bladder caused by bladder outflow obstruction (male) or
      atherosclerosis (male/female). The mechanisms by which chronic ischemia initiates
      and causes LUTS and progressive bladder dysfunction, and the time course of the
      effects, are incompletely known. Bladder ischemia and repeated
      ischemia/reperfusion during a micturition cycle may produce oxidative stress,
      leading to denervation of the bladder and the expression of tissue damaging
      molecules in the bladder wall. This may be responsible for the development of
      detrusor overactivity progressing to detrusor underactivity and inability to
      empty the bladder. The extent of bladder dysfunction in chronic bladder ischemia
      may depend on the degree and duration of ischemia. To prevent chronic bladder
      ischemia caused by atherosclerosis and to treat its consequences, more
      pathophysiological knowledge is needed. Several animal models of atherosclerosis
      induced chronic bladder ischemia are available and should be useful tools for
      further research.

PMID- 24292975
TI  - Pathologic reporting of lymph node metastases in differentiated thyroid cancer: a
      call to action for the College of American Pathologists.
AB  - Lymph nodes in differentiated thyroid cancer have many different histomorphologic
      features. The current AJCC staging system does not distinguish between different
      lymph node characteristics and is based entirely on the presence of metastatic
      disease to upstage pN0 to pN1. However, clinicians involved in the management of
      thyroid cancer recognize that there is a difference in the clinical significance
      of finding macroscopic versus microscopic nodes. There appears to be a difference
      in disease biology that allows lymph nodes to reach different sizes and to
      manifest disease extension outside the capsule, which has led clinicians, and
      even clinical practice guidelines, to stratify nodal metastases on the basis of
      these features. The inherent presumption is that all lymph node metastases in
      differentiated thyroid cancer do not have the same clinical significance with
      respect to the risk of recurrence and the risk of death. However, the College of
      American Pathology (CAP) has not mandated that pathologists include these
      findings as part of their standard reporting protocol in thyroid cancer. In order
      to arm clinicians with the tools to design clinical trials and to make important
      patient management decisions in the presence of lymph node metastases, it is
      imperative that the CAP adopt a strategy for more detailed reporting that is
      similar to the protocol currently utilized in breast cancer pathologic reporting.

PMID- 24292976
TI  - O-GlcNAcylation as a novel ammonia-induced posttranslational protein modification
      in cultured rat astrocytes.
AB  - Hepatic encephalopathy (HE) is a clinical manifestation of a low grade cerebral
      edema with a mutual interrelationship between osmotic- and oxidative stress. This
      leads to RNA oxidation and posttranslational protein modifications such as
      protein tyrosine nitration with pathophysiological relevance. Here, we report on
      O-GlcNAcylation as another ammonia-induced posttranslational protein modification
      in cultured rat astrocytes. NH4Cl induced O-GlcNAcylation of distinct proteins
      (25-250 kDa) in astrocytes in a dose- and time-dependent manner. Exposure of
      astrocytes to NH4Cl (5 mmol/l) for 48 h and 72 h significantly increased protein
      O-GlcNAcylation by about 2-fold and 4-fold, respectively. NH4Cl at a
      concentration of 1 mmol/l was sufficient to double protein O-GlcNAcylation in
      astrocytes after 72 h as compared to untreated controls. Ammonia-induced protein
      O-GlcNAcylation was sensitive towards glutamine-synthetase inhibition by
      methionine sulfoximine (MSO), but was not induced by hypoosmolarity (205
      mosmol/l) or CH3NH3Cl (5 mmol/l). Increased protein O-GlcNAcylation in NH4Cl (5
      mmol/l, 48 h)-treated astrocytes was fully reversible within 24 h after
      withdrawal of NH4Cl from culture medium. Amongst the proteins which are O
      GlcNAcylated in response to ammonia, GAPDH was identified. It is concluded that
      ammonia induces reversible protein O-GlcNAcylation in astrocytes that depends on
      glutamine synthesis but not on astrocyte swelling per se or ammonia-induced pH
      changes. In view of the complex involvement of O-GlcNAcylation in cell
      regulation, such as energy metabolism, apoptosis and circadian rhythmicity and in
      pathologies, such as neurodegenerative diseases, O-GlcNAcylation might contribute
      to the pathophysiology of hepatic encephalopathy. 

PMID- 24292977
TI  - Tristetraprolin down-regulates IL-23 expression in colon cancer cells.
AB  - Interleukin 23 (IL-23) is an inflammatory cytokine that plays an important role
      in tumor promotion. Expression of IL-23 is increased in cancer cells and
      correlates with tumor progression. However, the mechanisms regulating IL-23
      expression in cancer cells are still unclear. Here we report that tristetraprolin
      (TTP), an AU-rich element (ARE)-binding protein, inhibits IL-23 production in
      CT26 mouse colon cancer cells. Overexpression of TTP decreased the stability of
      IL-23 mRNA and the expression level of IL-23 in CT26 cells. Conversely,
      inhibition of TTP by siRNA increased IL-23 production. TTP destabilized a
      luciferase mRNA reporter containing the IL-23 mRNA 3'UTR, which contains five
      AREs. Analyses of deletion and point mutants of the IL-23 mRNA 3'UTR demonstrated
      that the ARE cluster between the third and fifth AREs was responsible for TTP
      mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift
      assay confirmed that TTP binds to this ARE cluster. Taken together, these results
      demonstrate that TTP acts as a negative regulator of IL-23 gene expression in
      mouse colon cancer cells and suggest its potential application as a novel
      therapeutic target to control IL-23-mediated tumor promotion. 

PMID- 24292978
TI  - Graphene films show stable cell attachment and biocompatibility with electrogenic
      primary cardiac cells.
AB  - Graphene has attracted substantial attention due to its advantageous
      materialistic applicability. In the present study, we tested the biocompatibility
      of graphene films synthesized by chemical vapor deposition with electrogenic
      primary adult cardiac cells (cardiomyocytes) by measuring the cell properties
      such as cell attachment, survival, contractility and calcium transients. The
      results show that the graphene films showed stable cell attachment and excellent
      biocompatibility with the electrogenic cardiomyocytes, suggesting their useful
      applications for future cell biology studies. 

PMID- 24292979
TI  - Clinical outcomes of platelet rich plasma (PRP) as an adjunct to microfracture
      surgery in osteochondral lesions of the talus.
AB  - PURPOSE: To compare the effect of arthroscopic microfracture surgery alone or in
      combination with platelet rich plasma (PRP) on functional outcomes in
      osteochondral lesions of the talus. METHODS: A total of 35 patients were included
      in the study. Control subjects (n = 16) received treatment with microfracture
      surgery alone, while the remaining patients (PRP group, n = 19) were also given
      PRP. After an average follow-up of 16.2 months (range 12-24 months), patients
      were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS)
      scoring system, Foot and Ankle Ability Measure (FAAM), and the visual analogue
      scale (VAS) for pain. RESULTS: At baseline, AOFAS and FAAM scores were similar in
      the two groups, whereas pain scores (VAS) were higher in those who were assigned
      to combined treatment. Despite the latter finding, the combined treatment with
      PRP resulted in better outcomes in terms of functional scores [AOFAS, 89.2 +/-
      3.9 vs. 71.0 +/- 10.2, (p = 0.001); FAAM overall pain domain, 1.0 (1.0-2.0) vs.
      2.5 (1.0-4.0), (p = 0.04); FAAM 15-min walking domain, 1.0 (1.0-2.0) vs. 2.0 (1.0
      4.0) (p = 0.001)]; and pain-related scores [VAS, 2.2 +/- 0.8 vs. 3.8 +/- 1.2, (p
      = 0.001)] as compared to arthroscopic microfracture surgery alone. CONCLUSIONS:
      PRP as an adjunct to arthroscopic microfracture surgery for the treatment of
      osteochondral lesions of the talus resulted in improved functional score status
      in the medium-term. Further studies to determine the long-term efficacy of this
      approach were warranted. LEVEL OF EVIDENCE: II.

PMID- 24292981
TI  - Erratum to: Reliability of the imaging software in the preoperative planning of
      the open-wedge high tibial osteotomy.

PMID- 24292980
TI  - Local infiltration analgesia following total knee arthroplasty: effect on post
      operative pain and opioid consumption--a meta-analysis.
AB  - INTRODUCTION: Local infiltration analgesia (LIA) is a popular method for
      decreasing post-operative pain after total knee arthroplasty (TKA). The goal of
      this meta-analysis is to compare the effect of LIA with placebo on the intensity
      of post-operative pain and the consumption of opioids. METHODS: A search was
      performed in the PubMed/MEDLINE, Cochrane, EMBASE and TRIP databases. All (quasi)
      randomized controlled trials (RCTs) were included. LIA consists of intra
      operative infiltration with at least one analgesic component. Data were pooled
      using Cochrane software. RESULTS: Seven placebo-controlled RCTs were included,
      involving 405 TKAs. On the first post-operative day, LIA provides an average
      decrease in VAS scores at rest of 12.3 % compared to placebo. Six RCTs studied
      opioid consumption in patients following TKA. There was a decrease in opioid
      consumption of 14.8 % compared to placebo 24 h after surgery. This suggests a
      reduced pain perception due to LIA. On the second post-operative day, the effect
      on both outcome measures was diminished and no longer significant. Heterogeneity
      between the studies was 71 % for pain and 39 % for opioid consumption (p = 0.002
      and p = 0.0005). No major complications were reported with the use of LIA.
      CONCLUSION: LIA might be able to decrease pain and the use of opioids on the
      first post-operative day following TKA. However, due to the high level of
      heterogeneity between the studies, no firm conclusions can be drawn. LEVEL OF
      EVIDENCE: Meta-analysis, Level II.

PMID- 24292982
TI  - Delusions of expertise: the high standard of proof needed to demonstrate skills
      at horserace handicapping.
AB  - Gamblers who participate in skill-oriented games (such as poker and sports
      betting) are motivated to win over the long-term, and some monitor their betting
      outcomes to evaluate their performance and proficiency. In this study of
      Australian off-track horserace betting, we investigated which levels of sustained
      returns would be required to establish evidence of skill/expertise. We modelled a
      random strategy to simulate 'naive' play, in which equal bets were placed on
      randomly selected horses using a representative sample of 211 weekend races.
      Results from a Monte Carlo simulation yielded a distribution of return-on
      investments for varying number of bets (N), showing surprising volatility, even
      after a large number of repeated bets. After adjusting for the house advantage, a
      gambler would have to place over 10,000 bets in individual races with net returns
      exceeding 9 % to be reasonably considered an expert punter (alpha = .05).
      Moreover, a record of fewer bets would require even greater returns for
      demonstrating expertise. As such, validated expertise is likely to be rare among
      race bettors. We argue that the counter-intuitively high threshold for
      demonstrating expertise by tracking historical performance is likely to
      exacerbate known cognitive biases in self-evaluation of expertise.

PMID- 24292983
TI  - Just like the lottery? Player behaviour and anomalies in the market for football
      pools.
AB  - Football pools were an antecedent to lotto in providing a long-odds, high-prize
      gambling opportunity for a mass market in Europe. Even after lotto has become
      well established, pools games continue to occupy a significant niche in the
      gaming market in several jurisdictions, most notably Spain. This paper employs 23
      years of sales data from the national pools game in Spain to investigate
      similarities between the behaviour of lotto players and pools players. It
      observes similar phenomena as have been noted in lotto sales studies, including
      strong sensitivity of sales to the size of jackpot on offer, significant habit
      effects, a halo effect whereby there is some short-term persistence in increased
      sales whenever a high jackpot is offered (even after jackpot size has returned to
      normal), and a tendency to jackpot fatigue (over time, the size of the jackpot
      has to be increased to more than before to stimulate the same increase in sales).
      Notwithstanding that the football pools are marketed as based on knowledge and
      understanding of sport whereas lotto is a pure numbers game, modelling sales of
      the pools therefore yields findings very similar to those reported in the
      literature on lotto. This suggests that both sets of players share common
      psychological and cognitive traits and economic motivation. Those responsible for
      promoting pools should therefore be able to draw on findings from the much more
      extensive literature on lotto when formulating strategy in terms of game design
      and marketing. 

PMID- 24292984
TI  - Physicochemical parameters aid microbial community? A case study from marine
      recreational beaches, Southern India.
AB  - A total of 176 (water and sediment) samples from 22 stations belonging to four
      different (urban, semi-urban, rural, and holy places) human habitations of Tamil
      Nadu beaches were collected and analyzed for physiochemical and microbial
      parameters during 2008-2009. Bacterial counts were two- to tenfold higher in
      sediments than in water due to strong bacterial aggregations by dynamic
      flocculation and rich organic content. The elevated bacterial communities during
      the monsoon explain rainfalls and several other wastes from inlands. Coliform
      counts drastically increased at holy and urban places due to pilgrimage and other
      ritual activities. Higher values of the pollution index (PI) ratio (>1) reveals,
      human fecal pollutions affect the water quality. The averaged PI ratio shows a
      substantial higher microbial contamination in holy places than in urban areas and
      the order of decreasing PI ratios observed were: holy places > urban areas > semi
      urban areas > rural areas. Correlation and factor analysis proves microbial
      communities were not related to physicochemical parameters. Principal component
      analysis indicates 55.32 % of the total variance resulted from human/animal fecal
      matters and sewage contaminants whereas 19.95 % were related to organic contents
      and waste materials from the rivers. More than 80 % of the samples showed a
      higher fecal coliform and Streptococci by crossing the World Health
      Organization's permissible limits. 

PMID- 24292985
TI  - Selecting the optimum plot size for a California design-based stream and wetland
      mapping program.
AB  - Accurate estimates of the extent and distribution of wetlands and streams are the
      foundation of wetland monitoring, management, restoration, and regulatory
      programs. Traditionally, these estimates have relied on comprehensive mapping.
      However, this approach is prohibitively resource-intensive over large areas,
      making it both impractical and statistically unreliable. Probabilistic (design
      based) approaches to evaluating status and trends provide a more cost-effective
      alternative because, compared with comprehensive mapping, overall extent is
      inferred from mapping a statistically representative, randomly selected subset of
      the target area. In this type of design, the size of sample plots has a
      significant impact on program costs and on statistical precision and accuracy;
      however, no consensus exists on the appropriate plot size for remote monitoring
      of stream and wetland extent. This study utilized simulated sampling to assess
      the performance of four plot sizes (1, 4, 9, and 16 km(2)) for three geographic
      regions of California. Simulation results showed smaller plot sizes (1 and 4
      km(2)) were most efficient for achieving desired levels of statistical accuracy
      and precision. However, larger plot sizes were more likely to contain rare and
      spatially limited wetland subtypes. Balancing these considerations led to
      selection of 4 km(2) for the California status and trends program.

PMID- 24292986
TI  - XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in
      breast cancer patients.
AB  - Radiotherapy is an important weapon in the treatment of breast cancer, but normal
      tissue injury after radiotherapy can be a threat for patients. Genetic markers
      conferring the ability to identify hyper-sensitive patients at risk of normal
      tissue injury in advance would considerably improve therapy. Association studies
      on genetic variation and occurrence of normal tissue injury can help us identify
      such markers, but previous studies on the association between XRCC1 R399Q
      polymorphism and risk of normal tissue injury after radiotherapy in breast cancer
      patients report conflicting findings. We performed a meta-analysis to
      comprehensively evaluate the association between XRCC1 R399Q polymorphism and
      risk of normal tissue injury after radiotherapy in breast cancer patients. The
      pooled odds ratios (ORs) with their 95% confidence interval (95% CIs) were
      calculated to assess the strength of the association. Fourteen case-control
      studies with a total of 2,448 breast cancer cases were finally included into the
      meta-analysis. Overall, XRCC1 R399Q polymorphism was significantly associated
      with increased risk of normal tissue injury after radiotherapy under all three
      models (for QQ versus RR: fixed-effects OR = 1.06, 95% CI 1.00-1.13, P = 0.050;
      for RQ versus RR: fixed-effects OR = 1.05, 95% CI 1.00-1.10, P = 0.047; for QQ/RQ
      versus RR: fixed-effects OR = 1.26, 95% CI 1.01-1.58, P = 0.041). The meta
      analysis suggests that XRCC1 R399Q polymorphism was significantly associated with
      increased risk of normal tissue injury after radiotherapy in breast cancer
      patients, and XRCC1 R399Q polymorphism is a genetic marker of normal tissue
      injury after radiotherapy in breast cancer patients.

PMID- 24292988
TI  - Fetal alcohol spectrum disorders and childhood cancer: a concise review of case
      reports and future research considerations.
AB  - We reviewed the published literature on the relationship between childhood cancer
      and fetal alcohol spectrum disorders (FASD). A Pub Med search identified 12
      subjects with the co-occurrence of FASD and cancer. We included an additional
      case from the author's institution. Neuroblastomas comprised 6 of the 13 (46%)
      case reports, yet neuroblastomas comprise only about 10% of childhood cancers (z
      = 4.1; P < 0.001). Other than rhabdomyosarcoma, no other cancer was reported more
      than once. Few cases of childhood cancer associated with FASD were identified
      likely due to under ascertainment of FASD.

PMID- 24292987
TI  - Comparative effectiveness of rosuvastatin versus simvastatin in primary
      prevention among new users: a cohort study in the French national health
      insurance database.
AB  - PURPOSE: Using the French claims database (Systeme National d'Information Inter
      Regimes de l'Assurance Maladie) linked to the hospital discharge database
      (Programme de Medicalisation des Systemes d'Information), this observational
      study compared the effectiveness of rosuvastatin and simvastatin prescribed at
      doses with close LDL-cholesterol-lowering potency on all-cause mortality and
      cardiovascular and cerebrovascular diseases (CCDs) in primary prevention.
      METHODS: This historical cohort included patients with no prior CCD, aged 40-79
      years, who initiated statin therapy with rosuvastatin 5 mg or simvastatin 20 mg
      in 2008-2009 in general practice. Follow-up started after a 1-year period used to
      select patients who regularly received the initial treatment. In an intention-to
      treat analysis, patients were followed up to December 2011. In a per-protocol
      analysis, they were censored prematurely when they discontinued their initial
      treatment. Adjustment for baseline covariates (age, deprivation index,
      comedications, comorbidities, prior hospital admissions) was carried out by a Cox
      proportional hazards model. In the per-protocol analysis, estimation was done by
      "inverse probability of censoring weighting" using additional time-dependent
      covariates. Analyses were gender-specific. RESULTS: A total of 106941 patients
      initiated statin therapy with rosuvastatin 5 mg and 56860 with simvastatin 20 mg.
      Mean follow-up was 35.8 months. For both genders and both types of analyses, the
      difference in incidence rates of mortality and/or CCD between rosuvastatin 5 mg
      and simvastatin 20 mg users was not statistically significant after adjustment
      (e.g., for CCD and/or mortality in men, in intention-to-treat analysis HR=0.94
      [95% CI=0.85-1.04], in per-protocol analysis HR=0.98 [0.87-1.10]). CONCLUSIONS:
      The results of this real-life study based on medico-administrative databases do
      not support preferential prescription of rosuvastatin compared to simvastatin for
      primary prevention of CCD.

PMID- 24292989
TI  - Conjugated and free sterols from black bean (Phaseolus vulgaris L.) seed coats as
      cholesterol micelle disruptors and their effect on lipid metabolism and
      cholesterol transport in rat primary hepatocytes.
AB  - Phytosterols have been widely studied for their cholesterol-lowering effect.
      Conjugated phytosterol forms have been found more active than free moieties.
      There are no reports about the sterol profile of black bean seed coats neither
      its effects on cholesterol metabolism. The aim of this research was to identify
      and quantify phytosterols from black bean seed coats and to determine their
      effects on cholesterol micellar solubility and on mRNA and key protein levels
      involved in lipid/cholesterol metabolism and cholesterol transport in primary rat
      hepatocytes. Free phytosterols, acylated steryl glycosides, and steryl glycosides
      were extracted from black bean seed coats. They were identified through HPLC-MS
      TOF and quantified through HPLC equipped with UV-visible and evaporative light
      scattering detectors. Free and conjugated phytosterols from the coats
      significantly increased the inhibitory effect of cholesterol micelle formation
      compared with stigmasterol, which was used as control (P < 0.05). In addition,
      phytosterols of black bean seed coat decreased lipogenesis by the downregulation
      of lipogenic proteins such as sterol regulatory element-binding protein 1 and
      fatty acid synthesis (FAS) in primary rat hepatocytes. Regarding beta-oxidation,
      phytosterols upregulated the expression of carnitine palmitoyltransferase I and
      promoted the beta-oxidation of long-chain fatty acids. Phytosterols inhibited
      cholesterol micellar solubility and reduced the activation of the liver X
      receptor, decreasing hepatic FAS and promoting hepatic beta-oxidation of long
      chain fatty acids. 

PMID- 24292990
TI  - Responses to FTO genetic test feedback for obesity in a sample of overweight
      adults: a qualitative analysis.
AB  - Current evidence indicates that genetic testing for obesity risk has limited
      affective or behavioral impact, but few studies have explored the effects among
      individuals who self-identify as having weight problems. Here, we report findings
      from in-depth telephone interviews with seven overweight or obese volunteers who
      were genotyped for one weight-related gene (FTO), which may offer interesting
      insights into motivations to seek out genetic testing and immediate reactions to
      it. All participants had a BMI > 25. The gene test identified one participant as
      homozygous for the 'higher-risk' variant (AA), three heterozygous (AT), and three
      homozygous for the 'lower-risk' variant (TT) of FTO. All participants said they
      took part to find an explanation for their personal struggle with weight control.
      Those with one or two higher-risk variants experienced relief and saw the result
      as confirming their private assumption that they were susceptible to weight gain
      for reasons perceived as 'external' to them. However, at the same time, they
      described themselves as more motivated to overcome their genetic predisposition.
      Those with lower-risk variants reported brief disappointment, but then focused on
      alternative explanations, reinforcing the multifactorial nature of obesity.
      Despite objectively low 'information value,' all individuals derived some
      'personal' benefit from FTO genetic test feedback. However, improving education
      about the multifactorial nature of complex conditions is important to decrease
      polarized thinking and associated genetic determinism and stigma to derive the
      greatest benefits of novel genetic technologies for individuals and their health.

PMID- 24292991
TI  - Effect of clarithromycin in patients with suspected Gram-negative sepsis: results
      of a randomized controlled trial.
AB  - BACKGROUND: A previous randomized study showed that clarithromycin decreases the
      risk of death due to ventilator-associated pneumonia and shortens the time until
      infection resolution. The efficacy of clarithromycin was tested in a larger
      population with sepsis. METHODS: Six hundred patients with systemic inflammatory
      response syndrome due to acute pyelonephritis, acute intra-abdominal infections
      or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized,
      multicentre trial. Clarithromycin (1 g) was administered intravenously once daily
      for 4 days consecutively in 302 patients; another 298 patients were treated with
      placebo. Mortality was the primary outcome; resolution of infection and
      hospitalization costs were the secondary outcomes. RESULTS: The groups were well
      matched for demographics, disease severity, microbiology and appropriateness of
      the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths)
      in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671).
      Nineteen out of 26 placebo-treated patients with septic shock and multiple organ
      dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated
      patients (53.6%, P = 0.020). The median time until resolution of infection was 5
      days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in
      the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of
      hospitalization was lower after treatment with clarithromycin (P = 0.044).
      Serious adverse events were observed in 1.3% and 0.7% of placebo- and
      clarithromycin-treated patients, respectively (P = 0.502). CONCLUSIONS:
      Intravenous clarithromycin did not affect overall mortality; however,
      administration shortened the time to resolution of infection and decreased the
      hospitalization costs.

PMID- 24292992
TI  - Predicting the restricted mean event time with the subject's baseline covariates
      in survival analysis.
AB  - For designing, monitoring, and analyzing a longitudinal study with an event time
      as the outcome variable, the restricted mean event time (RMET) is an easily
      interpretable, clinically meaningful summary of the survival function in the
      presence of censoring. The RMET is the average of all potential event times
      measured up to a time point tau and can be estimated consistently by the area
      under the Kaplan-Meier curve over $[0, ?tau ]$. In this paper, we study a class
      of regression models, which directly relates the RMET to its "baseline"
      covariates for predicting the future subjects' RMETs. Since the standard Cox and
      the accelerated failure time models can also be used for estimating such RMETs,
      we utilize a cross-validation procedure to select the "best" among all the
      working models considered in the model building and evaluation process. Lastly,
      we draw inferences for the predicted RMETs to assess the performance of the final
      selected model using an independent data set or a "hold-out" sample from the
      original data set. All the proposals are illustrated with the data from the an
      HIV clinical trial conducted by the AIDS Clinical Trials Group and the primary
      biliary cirrhosis study conducted by the Mayo Clinic. 

PMID- 24292993
TI  - Alterations in the levels of vesicular trafficking proteins involved in HIV
      replication in the brains and CSF of patients with HIV-associated neurocognitive
      disorders.
AB  - Human immunodeficiency virus (HIV) associated neurocognitive disorders (HAND)
      remain prevalent despite improved antiretroviral therapies. A HAND-specific
      biomarker indicative of neuropsychological impairment (NPI) would give insight
      into disease progression and aid clinicians in designing therapy. Endosomal
      sorting complex required for transport (ESCRT) proteins such as tumor
      susceptibility gene (TSG)-101, vacuolar protein sorting (VPS)-4 and LIP-5 are
      important for HIV replication and recently antiviral interferon stimulated gene
      (ISG)-15 was proposed as a biomarker for CNS injury. Here, we analyzed a well
      characterized cohort of HIV+ cerebral spinal fluid (CSF) and postmortem brain
      specimens for multiple vesicular trafficking proteins and a related innate immune
      protein, ISG-15, TSG-101, VPS-4 and LIP-5. All protein levels trended higher with
      increased NPI and neuropathology. ISG-15 CSF levels were increased in HIV
      encephalitis (HIVE) compared to normal cases, and three quarters of HIVE samples
      had above average CSF ISG-15 levels. VPS-4 CSF levels were increased in NPI/NPI-O
      compared to normal patients. VPS-4 CSF levels in HIV-associated dementia were
      equivalent to that of normal patients. LIP-5 CSF levels positively correlate with
      ISG-15 levels, and higher than average ISG-15 levels indicate elevated viral
      load. Immunoblot and immunohistochemical analyses show increased expression of
      ISG-15, VPS-4 and LIP-5 in neuronal cell bodies and astroglial cells. ESCRT
      protein CSF levels analyzed in conjunction with viral load may be indicative of
      NPI stage, and may aid in the diagnosis and design of therapies for HIV patients.
      Further studies on the ESCRT protein expression during HIV infection may lead to
      a promising biomarker for predicting progression of NPI. 

PMID- 24292994
TI  - Expression of cellular retinoic acid-binding protein-I (CRABP-I) in the
      cerebrospinal fluid of adult onset moyamoya disease and its association with
      clinical presentation and postoperative haemodynamic change.
AB  - OBJECTIVE: The elevation of cellular retinoic acid-binding protein-I (CRABP-I)
      has been suggested as a candidate in the pathogenesis of paediatric moyamoya
      disease (MMD). However, few studies have addressed CRABP-I in adult onset MMD.
      The aim of this study was to examine the expression of CRABP-I in the
      cerebrospinal fluid (CSF) of adult onset MMD, and to evaluate its association
      with clinical presentation and postoperative haemodynamic change. METHODS: This
      study examined the CSF from 103 patients: bilateral MMD, n=58 (56.3%); unilateral
      MMD, n=19 (18.4%); atherosclerotic cerebrovascular disease (ACVD), n=21 (20.4%);
      and control group, n=5 (4.9%). The intensity of CRABP-I was confirmed by western
      blotting and expressed as the median (25th-75th percentile). The differences in
      CRABP-I expression according to disease entity (unilateral MMD vs bilateral MMD
      vs ACVD), initial presenting symptoms (haemorrhage vs ischaemia) and
      postoperative haemodynamic change (vascular reserve in single photon emission CT
      and basal collateral vessels in digital subtraction angiography) were analysed.
      RESULTS: CRABP-I intensities in bilateral MMD (1.45(0.86-2.52)) were
      significantly higher than in unilateral MMD (0.91(0.78-1.20)) (p=0.044) or ACVD
      (0.85(0.66-1.11)) (p=0.004). No significant differences were noted based on the
      initial presenting symptoms (p=0.687). CRABP-I was not associated with
      improvement in vascular reserve (p=0.327), but with decrease in basal collateral
      vessels (p=0.023) postoperatively. CONCLUSIONS: Higher CRABP-I in the CSF can be
      associated with typical bilateral MMD pathogenesis in adults. Additionally,
      postoperative basal collateral change may be related to the degree of CRABP-I
      expression.

PMID- 24292996
TI  - Time to next relapse as a primary endpoint in neuromyelitis optica clinical
      trials.

PMID- 24292995
TI  - Time to 12-month remission and treatment failure for generalised and unclassified
      epilepsy.
AB  - OBJECTIVES: To develop prognostic models for time to 12-month remission and time
      to treatment failure after initiating antiepileptic drug monotherapy for
      generalised and unclassified epilepsy. METHODS: We analysed data from the
      Standard and New Antiepileptic Drug (arm B) study, a randomised trial that
      compared initiating treatment with lamotrigine, topiramate and valproate in
      patients diagnosed with generalised or unclassified epilepsy. Multivariable
      regression modelling was used to investigate how clinical factors affect the
      probability of achieving 12-month remission and treatment failure. RESULTS:
      Significant factors in the multivariable model for time to 12-month remission
      were having a relative with epilepsy, neurological insult, total number of tonic
      clonic seizures before randomisation, seizure type and treatment. Significant
      factors in the multivariable model for time to treatment failure were treatment
      history (antiepileptic drug treatment prior to randomisation), EEG result,
      seizure type and treatment. CONCLUSIONS: The models described within this paper
      can be used to identify patients most likely to achieve 12-month remission and
      most likely to have treatment failure, aiding individual patient risk
      stratification and the design and analysis of future epilepsy trials.

PMID- 24292997
TI  - Dystrophin levels and clinical severity in Becker muscular dystrophy patients.
AB  - OBJECTIVE: Becker muscular dystrophy (BMD) is characterised by broad clinical
      variability. Ongoing studies exploring dystrophin restoration in Duchenne
      muscular dystrophy ask for better understanding of the relation between
      dystrophin levels and disease severity. We studied this relation in BMD patients
      with varying mutations, including a large subset with an exon 45-47 deletion.
      METHODS: Dystrophin was quantified by western blot analyses in a fresh muscle
      biopsy of the anterior tibial muscle. Disease severity was assessed using
      quantitative muscle strength measurements and functional disability scoring. MRI
      of the leg was performed in a subgroup to detect fatty infiltration. RESULTS: 33
      BMD patients participated. No linear relation was found between dystrophin levels
      (range 3%-78%) and muscle strength or age at different disease milestones, in
      both the whole group and the subgroup of exon 45-47 deleted patients. However,
      patients with less than 10% dystrophin all showed a severe disease course. No
      relation was found between disease severity and age when analysing the whole
      group. By contrast, in the exon 45-47 deleted subgroup, muscle strength and
      levels of fatty infiltration were significantly correlated with patients' age.
      CONCLUSIONS: Our study shows that dystrophin levels appear not to be a major
      determinant of disease severity in BMD, as long as it is above approximately 10%.
      A significant relation between age and disease course was only found in the exon
      45-47 deletion subgroup. This suggests that at higher dystrophin levels, the
      disease course depends more on the mutation site than on the amount of the
      dystrophin protein produced.

PMID- 24292998
TI  - Natural course of idiopathic normal pressure hydrocephalus.
AB  - OBJECTIVES: The natural course of idiopathic normal pressure hydrocephalus (iNPH)
      has not been thoroughly studied. The consequences of postponing shunt treatment
      are largely unknown. We aimed to describe the effects of waiting for more than 6
      months before surgery and to compare the outcome with that seen in patients who
      waited for less than 3 months. METHODS: 33 patients (iNPHDelayed) underwent an
      initial investigation (Pre-op 1), followed by re-examination, just prior to
      surgery, after waiting for at least 6 months (Pre-op 2). Outcome was evaluated
      after 3 months of treatment. 69 patients who were surgically treated within 3
      months after Pre-op 1 and who were also evaluated after 3 months of treatment
      constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH
      scale and the modified Rankin Scale (mRS). iNPHDelayed patients were
      prospectively studied with regard to outcome, whereas the comparison group
      iNPHEarly was defined and analysed retrospectively. RESULTS: iNPHDelayed patients
      deteriorated significantly during their wait for surgery, with progression of
      symptom severity ranging from +7 to -47 on the iNPH scale, and from 0 to +3 on
      the mRS (both p<0.001). The magnitude of change after surgery was similar in the
      groups, but since the symptoms of iNPHDelayed patients had worsened while
      waiting, their final outcome was significantly poorer. CONCLUSIONS: The natural
      course of iNPH is symptom progression over time, with worsening in gait, balance
      and cognitive symptoms. This deterioration is only partially reversible. To
      maximise the benefits of shunt treatment, surgery should be performed soon after
      diagnosis.

PMID- 24292999
TI  - Efficacy of subcutaneous interferon beta-1a on MRI outcomes in a randomised
      controlled trial of patients with clinically isolated syndromes.
AB  - AIM: The REbif FLEXible dosing in early MS (REFLEX) study compared several brain
      MRI outcomes in patients presenting with clinically isolated syndromes suggestive
      of multiple sclerosis and treated with two dose-frequencies of subcutaneous
      interferon (IFN) beta-1a or placebo. METHODS: Patients were randomised (1:1:1) to
      IFN beta-1a, 44 ug subcutaneously three times a week or once a week, or placebo
      three times a week for up to 24 months. MRI scans were performed every 3 months,
      or every 6 months if the patient developed clinically definite multiple
      sclerosis. End points analysed included: number of combined unique active lesions
      per patient per scan; numbers and volumes of new T2, T1 hypointense and
      gadolinium-enhancing (Gd+) lesions per patient per scan; and brain volume.
      RESULTS: 517 patients were randomised (intent-to-treat population: subcutaneous
      IFN beta-1a three times a week, n=171; subcutaneous IFN beta-1a once a week,
      n=175; placebo, n=171). Combined unique active lesions were lower in patients
      treated with subcutaneous IFN beta-1a versus placebo (mean (SD) lesions per
      patient per scan: three times a week 0.6 (1.15); once a week 1.23 (4.26); placebo
      2.70 (5.23); reduction versus placebo: three times a week 81%; once a week 63%;
      p<0.001) and with three times a week versus once a week (48% reduction; p=0.002).
      The mean numbers of new T2, T1 hypointense and Gd+ lesions were all significantly
      lower in the two active treatment arms compared with placebo (p<=0.004 for three
      times a week or once a week) and in the three times a week group compared with
      once a week (p<=0.012). CONCLUSIONS: Both subcutaneous IFN beta-1a 44 ug regimens
      improved MRI outcomes versus placebo, with the three times a week regimen having
      a more pronounced effect than once a week dosing. TRIAL REGISTRATION:
      clinicaltrial.gov identifier, NCT00404352.

PMID- 24293000
TI  - Complications to invasive epilepsy surgery workup with subdural and depth
      electrodes: a prospective population-based observational study.
AB  - OBJECTIVE: In some patients who undergo presurgical workup for drug-resistant
      epilepsy invasive seizure monitoring is needed to define the seizure onset zone
      and delineate eloquent cortex. Such procedures carry risks for complications
      causing permanent morbidity and even mortality. In this study, prospective data
      on complications in a national population-based sample were analysed. DESIGN:
      Complication data from the prospective Swedish National Epilepsy Surgery Register
      were analysed for 271 patients in whom therapeutic surgery was preceded by
      invasive monitoring 1996-2010. RESULTS: Complications occurred in 13/271 patients
      (4.8%). Subdural grids carried the highest risk of complications (7.4%). There
      was no surgical mortality or permanent morbidity. Subdural haematomas were most
      common (n=7) followed by epidural haematomas (n=3). Valproate treatment and
      having a haematoma was associated with an OR of 1.53 (CI 0.38 to 6.12) compared
      to having a haematoma without valproate treatment. Having a complication during
      invasive monitoring was associated with a significant OR of 6.27 (CI 1.32 to
      29.9) of also having a complication at therapeutic surgery compared to the risk
      of having a complication only at surgery. CONCLUSIONS: In this prospective
      population-based epilepsy surgery series, the most common complications were
      haematomas, and subdural grids carried the highest risk. Close supervision and
      rapid interventions led to avoidance of permanent morbidity. The clinical
      implications of the slightly increased risk of haematomas with valproate
      treatment needs further investigation as does the finding of an increased risk
      for complications at epilepsy surgery for patients who had a complication during
      invasive monitoring.

PMID- 24293001
TI  - Cancer mortality and quantitative oil production in the Amazon region of Ecuador,
      1990-2010.
AB  - PURPOSE: Controversy persists over whether cancer risk is increased in
      communities surrounding oil fields, especially in the Oriente region of Ecuador.
      This ecologic study uses quantitative exposure data, updated mortality data, and
      improved statistical methods to study the impact of oil exploration and
      production activities on cancer mortality rates in the Oriente. METHODS: Cancer
      mortality rates in the Oriente in 1990 through 2010 were compared between seven
      cantons with active oil exploration and production as of 1990 and thirteen
      cantons with little or no such activities. Poisson regression was used to
      estimate mortality rate ratios (RRs) adjusted for age and sex. In a two-stage
      analysis, canton-specific log-RRs were regressed against quantitative estimates
      of cumulative barrels of oil produced and well-years per canton, adjusting for
      canton-level demographic and socioeconomic factors. RESULTS: Overall and site
      specific cancer mortality rates were comparable between oil-producing and non-oil
      producing cantons. For overall cancer mortality in males and females combined,
      the RR comparing oil-producing to non-oil-producing cantons was 0.85 [95 %
      confidence interval (CI) 0.72-1.00]. For leukemia mortality, the corresponding RR
      was 0.80 (95 % CI 0.57-1.13). Results also revealed no excess of mortality from
      acute non-lymphocytic, myeloid, or childhood leukemia. Standardized mortality
      ratios were consistent with RRs. Canton-specific RRs showed no pattern in
      relation to oil production volume or well-years. CONCLUSIONS: Results from this
      first ecologic study to incorporate quantitative measures of oil exploration and
      production showed no association between the extent of these activities and
      cancer mortality, including from cancers associated with benzene exposure.

PMID- 24293002
TI  - Interpretation and expectation in childhood anxiety disorders: age effects and
      social specificity.
AB  - Theory and treatment for childhood anxiety disorders typically implicates
      children's negative cognitions, yet little is known about the characteristics of
      thinking styles of clinically anxious children. In particular, it is unclear
      whether differences in thinking styles between children with anxiety disorders
      and non-anxious children vary as a function of child age, whether particular
      cognitive distortions are associated with childhood anxiety disorders at
      different child ages, and whether cognitive content is disorder-specific. The
      current study addressed these questions among 120 7-12 year old children (53%
      female) who met diagnostic criteria for social anxiety disorder, other anxiety
      disorder, or who were not currently anxious. Contrary to expectations, threat
      interpretation was not inflated amongst anxious compared to non-anxious children
      at any age, although older (10-12 year old) anxious children did differ from non
      anxious children on measures of perceived coping. The notion of cognitive-content
      specificity was not supported across the age-range. The findings challenge
      current treatment models of childhood anxiety, and suggest that a focus on
      changing anxious children's cognitions is not warranted in mid-childhood, and in
      late childhood cognitive approaches may be better focussed on promoting
      children's perceptions of control rather than challenging threat interpretations.

PMID- 24293003
TI  - Sleeping site selection by savanna chimpanzees in Ugalla, Tanzania.
AB  - We examined sleeping site selection by chimpanzees (Pan troglodytes) in the
      Ugalla savanna woodland area, western Tanzania, from 1994 to 2012. We established
      488 km of line transects and recorded 379 chimpanzee beds within 30 m
      perpendicular to the transects. Comparisons between 60 * 60 m(2) quadrats
      containing new and recent beds and the remaining quadrats without beds along the
      transects indicated that evergreen forests accounted for disproportionately more
      area in quadrats with beds than in those without beds during both the dry and
      rainy seasons. In Ugalla, chimpanzees coexist with lions (Panthera leo) and
      leopards (Panthera pardus). They may sleep in forests to reduce predation risk by
      these carnivores, as trees are dense and the canopy is high and closed. The angle
      of slope was steeper in quadrats containing beds than in those without beds
      during the dry season, whereas the angle was less steep in quadrats with beds
      than in those without beds during the rainy season. Additionally, fewer beds were
      found further from forests. The distance between beds and forests during the dry
      season was shorter than that during the rainy season. Chimpanzees may sleep in or
      near forests and on slopes because of water pools in the valley forests along the
      slopes during the dry season. Quadrats with beds were at slightly higher altitude
      than those without beds during the rainy season; however, the difference was not
      significant during the dry season. The number of beds found in or close to
      feeding trees was not related to the fruiting period. Sleeping site selection by
      chimpanzees may be affected by predation pressure and water availability in the
      savanna woodland area.

PMID- 24293004
TI  - Manipulation of hematopoietic stem cells for regenerative medicine.
AB  - Hematopoietic stem cells (HSCs) are defined by their capacity to self-renew and
      to differentiate into all blood cell lineages while retaining robust capacity to
      regenerate hematopoiesis. Based on these characteristics, they are widely used
      for transplantation and gene therapy. However, the dose of HSCs available for use
      in treatments is limited. Therefore, extensive work has been undertaken to expand
      HSCs in culture and to produce HSCs from embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs) in order to improve the efficiency and outcome of
      HSC-based therapies. Various surface markers have been characterized to improve
      the purification of HSCs and a huge number of cytokines and small-molecule
      compounds have been screened for use in the expansion of HSCs. In addition,
      attempts to generate not only HSCs but also mature blood cells from ESCs and
      iPSCs are currently ongoing. This review covers recent approaches for the
      purification, expansion or production of human HSCs and provides insight into
      problems that need to be resolved.

PMID- 24293005
TI  - Composition of antioxidants and amino acids in Stevia leaf infusions.
AB  - Stevia, a non-caloric natural sweetener with beneficial properties and
      considerable antioxidants and amino acids, is increasingly consumed as an
      infusion. This work evaluates the influence of the conditions (temperature: 50,
      70 or 90  degrees C and time: 1, 5, 20 or 40 min) applied to obtain Stevia
      infusions, on antioxidants (total phenols, flavonoids and antioxidant activity)
      and amino acids. The total concentration of the eleven amino acids found was
      11.70 mg/g in dried leaves and from 6.84 to 9.11 mg/g per gram of Stevia in
      infusions. However, infusions showed higher levels of certain amino acids
      (alanine, asparagine, leucine and proline), and greater values of the three
      antioxidant parameters in comparison with dry leaves. Temperature had more
      influence (minimum values at 50  degrees C and maximum at 90  degrees C) than
      time in the case of antioxidants. At 90  degrees C there were no important
      increases in the extraction of antioxidant compounds after 5 min; each gram of
      Stevia had 117 mg trolox (total antioxidant activity), 90 mg gallic acid (total
      phenols) and 56 mg catechin equivalents (flavonoids). Varying the temperature and
      time conditions no notable differences were observed in the concentrations of the
      majority of amino acids. However, the infusion treatment at 90  degrees C for 5
      min was the best, as it gave the highest yield of 8 of the 11 amino acids.
      Therefore, with respect to the compounds analyzed in this study, the best way to
      obtain Stevia leaf infusions is the same as the domestic process, almost boiling
      water for a short time.

PMID- 24293006
TI  - Memory deficits associated with sublethal cyanide poisoning relative to cyanate
      toxicity in rodents.
AB  - Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate,
      metabolites of which we sought to elucidate the differential toxicity effects on
      memory. Young 6-8 weeks old male rats were treated intraperitoneally with either
      2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1
      MUl/g bw saline, daily for 6 weeks. Short-term and long-term memories were
      assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an
      influence on short-term working memory with fewer correct arm entries (F(2, 19) =
      4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05)
      and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to
      NaCN and saline treatments. The long-term working memory was significantly
      impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01)
      and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative
      to NaOCN or vehicle treated animals. Reference memory was not affected by either
      cyanide or cyanate. Our study findings provide an experimental evidence for the
      biological plausibility that cassava cyanogens may induce cognition deficits.
      Differential patterns of memory deficits may reflect the differences in toxicity
      mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava
      cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

PMID- 24293008
TI  - Killing machines: three pore-forming proteins of the immune system.
AB  - The evolution of early multicellular eukaryotes 400-500 million years ago
      required a defensive strategy against microbial invasion. Pore-forming proteins
      containing the membrane-attack-complex-perforin (MACPF) domain were selected as
      the most efficient means to destroy bacteria or virally infected cells. The
      mechanism of pore formation by the MACPF domain is distinctive in that pore
      formation is purely physical and unspecific. The MACPF domain polymerizes,
      refolds, and inserts itself into bilayer membranes or bacterial outer cell walls.
      The displacement of surface lipid/carbohydrate molecules by the polymerizing
      MACPF domain creates clusters of large, water-filled holes that destabilize the
      barrier function and provide access for additional anti-bacterial or anti-viral
      effectors to sensitive sites that complete the destruction of the invader via
      enzymatic or chemical attack. The highly efficient mechanism of anti-microbial
      defense by a combined physical and chemical strategy using pore-forming MACPF
      proteins has been retargeted during evolution of vertebrates and mammals for
      three purposes: (1) to kill extracellular bacteria C9/polyC9 evolved in
      conjunction with complement, (2) to kill virus infected and cancer cells perforin
      1/polyperforin-1 CTL evolved targeted by NK and CTL, and (3) to kill
      intracellular bacteria transmembrane perforin-2/putative polyperforin-2 evolved
      targeted by phagocytic and nonphagocytic cells. Our laboratory has been involved
      in the discovery and description of each of the three pore-formers that will be
      reviewed here. 

PMID- 24293009
TI  - B cell regulation of anti-tumor immune response.
AB  - Our laboratory has been investigating the role of B cells on tumor immunity. We
      have studied the immune response in mice that are genetically lacking in B cells
      (BCDM) using a variety of syngeneic mouse tumors and compared immune responses in
      BCDM with those seen in wild type (WT) immunocompetent mice (ICM). A variety of
      murine tumors are rejected or inhibited in their growth in BCDM, compared with
      ICM, including the EL4 thymoma, and the MC38 colon carcinoma in C57BL/6 mice, as
      well as the EMT-6 breast carcinoma in BALB/c mice. In all three murine models,
      tumors show reduced growth in BCDM which is accompanied by increased T cell and
      NK cell infiltration, and a more vigorous Th1 cytokine response, and increased
      cytolytic T cell response in the absence of B cells. Reconstitution of the mice
      with B cells results in augmented tumor growth due to a diminished anti-tumor
      immune response and in reduction in CD8+ T cell and NK cell infiltration. Studies
      involving BCR transgenic mice indicated that B cells inhibit anti-tumor T cell
      responses through antigen non-specific mechanisms. More recent studies using the
      EMT-6 model demonstrated that both the number and function of Treg cells in ICM
      was increased relative to that seen in BCDM. Increased expansion of Treg cells
      was evident following EMT-6 implantation in ICM relative to that seen in non
      tumor-bearing mice or BCDM. The percentage and number of Tregs in spleen, tumor
      draining lymph nodes, and the tumor bed are increased in ICM compared with BCDM.
      Treg functional capacity as measured by suppression assays appears to be reduced
      in BCDM compared with ICM. In contrast to other described types of B regulatory
      activity, adoptive transfer of B cells can rescue tumor growth independently of
      the ability of B cells to secrete IL-10, and also independently of MHC-II
      expression. In experiments using the MC38 adenocarcinoma model, BCDM
      reconstituted with WT B cells support tumor growth while tumor growth continues
      to be inhibited in BCDM reconstituted with OX40L(-/-) B cells. This suggests that
      interaction between OX40 on T cells and OX40-ligand on B cells may be important
      in modulating anti-tumor immune response. Ongoing experiments in the laboratory
      indicate that B cells migrate to the site of tumor and acquire expression of
      immunosuppressive ligands and/or cytokines that contribute to the inhibition of
      anti-tumor immune response. Significant infiltration of human tumors by Treg
      cells as well as B cells suggests that observations made in murine systems may be
      applicable to human tumors as well. 

PMID- 24293010
TI  - (S)-tetrahydroisoquinoline alkaloid inhibits LPS-induced arachidonic acid release
      through downregulation of cPLA2 expression.
AB  - Sepsis, a systemic inflammatory response syndrome, remains a potentially lethal
      condition. (S)-1-alpha-Naphthylmethyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline (CKD712) is noted as a drug candidate for sepsis. Many
      studies have demonstrated its significant anti-inflammatory effects. Here we
      first examined whether CKD712 inhibits lipopolysaccharide (LPS)-induced
      arachidonic acid (AA) release in the RAW 264.7 mouse monocyte cell line, and
      subsequently, its inhibitory mechanisms. CKD712 reversed LPS-associated
      morphological changes in the RAW 264.7 cells, and inhibited LPS-induced release
      of AA in a concentrationdependent manner. The inhibition was apparently due to
      the diminished expression of a cytosolic form of phospholipase A2 (cPLA2) by
      CKD712, resulting from reduced NF-kappaB activation. Furthermore, CKD712
      inhibited the activation of ERK1/2 and SAP/JNK, but not of p38 MAPK. CKD712 had
      no effect on the activity or phosphorylation of cPLA2 and on calcium influx. Our
      results collectively suggest that CKD712 inhibits LPS-induced AA release through
      the inhibition of a MAPKs/NF-kappaB pathway leading to reduced cPLA2 expression
      in RAW 264.7 cells. 

PMID- 24293007
TI  - B-lymphocyte tolerance and effector function in immunity and autoimmunity.
AB  - B-lymphocytes are integral to host defense against microbial pathogens and are
      associated with many autoimmune diseases. The B-cell receptor implements B-cell
      self-tolerance based on the antigen specificity, and B-cell-activating factor
      receptor (BAFF-R) imposes homeostatic control. While shaping the repertoire, the
      immune tolerance process also culls mature B cells into distinct populations. The
      activation response of B cells is tailored to the type of pathogen attack and is
      facilitated by T-cell help via CD40/CD40L interaction and/or innate cell help via
      toll-like receptors in conjunction with BAFF receptors and ligands. Activated
      effector B cells not only produce antibodies, but also produce a variety of
      cytokines to enhance and suppress the immune response. Not surprisingly, B cells
      play multiple roles in both humoral and cellular immune responses during
      infection and autoimmune pathogenesis. Here, we discuss how gene expression and
      signaling networks regulate peripheral B-cell tolerance, B-cell effector
      functions and emerging therapies targeting B-cell signaling in autoimmune
      diseases. 

PMID- 24293011
TI  - The protein kinase 2 inhibitor CX-4945 regulates osteoclast and osteoblast
      differentiation in vitro.
AB  - Drug repositioning can identify new therapeutic applications for existing drugs,
      thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945
      regulates human cancer cell survival and angiogenesis. Here we found that CX-4945
      significantly inhibited the RANKL-induced osteoclast differentiation, but
      enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX
      4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression
      accompanied with suppression of Akt phosphorylation, but in contrast, it enhanced
      the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus
      a novel drug candidate for bone-related disorders such as osteoporosis. 

PMID- 24293012
TI  - Isolation of EpCAM(+)/CD133 (-) hepatic progenitor cells.
AB  - Progenitor cell-derived hepatocytes are critical for hepatocyte replenishment.
      Therefore, we established a line of human hepatic progenitor (HNK1) cells and
      determined their biological characteristics for experimental and therapeutic
      applications. HNK1 cells, isolated from human noncirrhotic liver samples with
      septal fibrosis, showed high expression of the hepatic progenitor cell (HPC)
      markers EpCAM, CK7, CK19, alpha-fetoprotein (AFP), CD90 (Thy1), and EFNA1.
      Expression of CD133 was very low. Ductular reactions at the periphery of
      cirrhotic nodules were immunohistochemically positive for these HPC markers,
      including EFNA1. Sodium butyrate, a differentiation inducer, induced hepatocyte
      like morphological changes in HNK1 cells. It resulted in down-regulation of the
      hepatic progenitor cell markers EpCAM, CK7, CK19, AFP, and EFNA1 and up
      regulation of mature hepatocyte markers, including albumin, CK8, and CK18.
      Furthermore, sodium butyrate treatment and a serial passage of HNK1 cells
      resulted in enhanced albumin secretion, ureagenesis, and CYP enzyme activity, all
      of which are indicators of differentiation in hepatocytes. However, HNK1 cells at
      passage 50 did not exhibit anchorage-independent growth capability and caused no
      tumors in immunodeficient mice, suggesting that they had no spontaneous malignant
      transformation ability. From this evidence, HNK1 cells were found to be
      EpCAM(+)/CD133(-) hepatic progenitor cells without spontaneous malignant
      transformation ability. We therefore conclude that HNK1 cells could be useful for
      experimental and therapeutic applications. 

PMID- 24293013
TI  - Impulsivity, gambling cognitions, and the gambler's fallacy in university
      students.
AB  - The present study explored the associations among impulsivity, gambling
      cognitions, and behavioral adherence to the gambler's fallacy in university
      students (N = 142). Both impulsivity and gambling cognitions were significant
      predictors of non-problem and problem gambler categories as defined the Problem
      Gambling Severity Index. A logistic regression analysis showed that the
      independent contribution of cognition was statistically significant but that the
      contribution of impulsivity was not. A behavioral measure of gambling was
      obtained by asking participants to play an online game of roulette for a maximum
      of 15 min. Only outside bets were permitted whereby participants were to bet on
      the color of the winning number. Adherence to the gambler's fallacy was indexed
      by the likelihood of betting on an alternation in the color of the winning number
      as the number of consecutive outcomes of the other color increased. Gambling
      cognitions and gender, but not impulsivity, were associated with adherence to the
      gambler's fallacy. Tracing the sources of specific influences on gambling
      behavior may benefit from a framework that distinguishes between "hot"
      (emotional) and "cold" (non-emotional) mechanisms that promote problem gambling.

PMID- 24293014
TI  - Desensitization of triggers and urge reprocessing for pathological gambling: a
      case series.
AB  - This case series introduces the desensitization of triggers and urge reprocessing
      (DeTUR), as a promising adjunctive therapy in addition to comprehensive treatment
      package for pathological gambling. This addiction protocol of eye movement
      desensitization and reprocessing was delivered to four male inpatients admitted
      to a 10-week inpatient program for pathological gambling. The therapist gave
      three 60-min weekly sessions of the DeTUR using bilateral stimulation (horizontal
      eye movements or alternative tactile stimuli) focusing on the hierarchy of
      triggering situations and the urge to initiate gambling behaviors. After
      treatment, self-reported gambling symptoms, depression, anxiety, and
      impulsiveness were all improved, and all the participants reported satisfaction
      with the therapy. They were followed up for 6 months and all maintained their
      abstinence from gambling and their symptomatic improvements. Given the efficiency
      (i.e., brevity and efficacy) of the treatment, a controlled study to confirm the
      effects of the DeTUR on pathological gambling would be justified.

PMID- 24293015
TI  - Adolescent online gambling in Cyprus: associated school performance and
      psychopathology.
AB  - This paper presents results from the study of gambling behaviors in a
      representative sample of Cypriot high-school students. The aim of the study was
      to ascertain epidemiology of adolescent online gambling in Cyprus and possible
      correlates. The sample consisted of 2,684 students (48.5% boys, 51.5% girls) from
      the first grades of junior (Gymnasium) and senior (Lyceum) high school. Our
      results indicate that gamblers presented with lower school achievement and
      related expectations while scoring consistently higher on measures of Internet
      addiction, parental bonding and psychopathology. Discriminant analysis revealed
      two profiles which explained the most variance in gambling behavior; the first
      profile that corresponded to more explained variance was the student with higher
      psychopathology, less prosocial behavior, higher Internet addiction score with
      higher frequencies of online activities and moderate levels of truancy and lower
      expectation of school achievement. The second profile was that of a student who
      reported less psychopathology, more prosocial behavior, less involvement with the
      Internet in general but skipped classes more and his prospects on finishing high
      school were even slimmer. These results will be utilized in the design of a
      comprehensive prevention program in an effort to combat online addictive
      behaviors.

PMID- 24293016
TI  - A passion for gambling: a generation-specific conceptual analysis and review of
      gambling among older adults in Canada.
AB  - The proliferation of gambling opportunities in Canada, coupled with an aging
      population, has led to an increased prevalence of gambling among older adults.
      Encouraged by this trend, gambling industries have modified their activities to
      attract and market to this group. Yet, older adults are not a homogeneous group.
      The life experiences, values, and attitudes shared by generations make a cohort
      specific analysis of gambling among older adults a worthwhile pursuit. Drawing
      from the Dualistic Model of Passion (Vallerand et al. in J Pers Soc Psychol
      85(4):756-767, 2003), we discuss the role of passion in shaping gambling
      behaviours, and the implications of a harmonious or obsessive passion on the
      benefits and risks to two distinct generations of older adults. Based on their
      generational attributes, we posit that members of the Silent Generation (those
      born between 1925 and 1942) stand to gain more from the benefits of recreational
      gambling, but also stand lose more from problem gambling, than their children's
      generation, the Baby Boomers (those born between 1942 and 1964). Preventative
      strategies to assist problem gambling seniors, along with recommendations for
      further research, are discussed. 

PMID- 24293017
TI  - Clinical and personality characteristics associated with post traumatic stress
      disorder in problem and pathological gamblers recruited from the community.
AB  - Problem and pathological gamblers (PPGs) are more likely than the general
      population to experience co-occurring psychiatric problems. However, the problem
      gambling literature has largely overlooked the importance of trauma and post
      traumatic stress disorder (PTSD) as a prevalent co-occurring condition among
      PPGs. This study examined clinical differences between PPGs with and without a
      history of co-occurring PTSD. Lifetime PPGs (N = 150) recruited from community
      sources completed clinical assessments including measures of problem gambling
      severity, co-occurring psychiatric conditions, gambling motivations and
      personality traits. Over 19% of the participants met criteria for a lifetime
      diagnosis of PTSD. Those presenting with PTSD histories were more likely to be
      women, and were more likely to have lifetime substance use disorder (abuse and/or
      dependence) and substance dependence, lifetime major depressive disorder, current
      dysthymic disorder, and lifetime and current anxiety disorder. Those with
      lifetime PTSD also were more likely to use gambling as a way to cope with
      negative emotions and experienced greater negative emotionality. Few PPGs (16%)
      had ever sought treatment for their gambling problems. PTSD is a prevalent
      condition among individuals with lifetime PPG recruited from the community, and
      is associated with greater psychiatric co-morbidity among these populations. More
      research is needed to further understand the relationship between gambling and
      trauma, and better outreach is needed to encourage these individuals to seek
      treatment.

PMID- 24293019
TI  - Can't see the (bamboo) forest for the trees: examining bamboo's fit within
      international forestry institutions.
AB  - Over the centuries, governments and international agencies have developed a wide
      range of institutions to manage timber resources and conserve values provided by
      treed lands. Concerns regarding the sustainable supply of timber have provided
      opportunities for the development of substitute resources; however, bamboo and
      other non-timber forest resources have not been a part of the development of
      these institutions. Bamboo is a unique Non-Timber Forest Product, as it is often
      classified as forest or timber, and therefore must adhere to the same regulations
      as timber. Given the recent global expansion of bamboo, it is timely to examine
      the interplay between bamboo and the traditional institutions of forest
      governance. This paper aims to contribute to debates regarding cognitive
      institutional constraints on the development of substitute natural resources
      using bamboo as a case study, with specific focus on the applicability of Forest
      Stewardship Council certification, timber legality verification and Reducing
      Emissions from Deforestation and Forest Degradation to bamboos. 

PMID- 24293018
TI  - Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery.
AB  - With recent studies showing increased prevalence of hepatitis delta (HDV) even in
      the US, Australia, and some countries in Europe, and very high prevalence in
      endemic regions, HDV infection is far from being a disappearing disease. Although
      immigrants from endemic countries have been shown to have increased risk, studies
      have clearly shown that the disease is not solely appearing in traditional high
      risk groups. Recent studies provide increasing evidence that sexual transmission
      may be an important factor in HDV infection spread. Based on the totality of
      evidence showing increased disease progression and substantially increased risk
      of cirrhosis in HDV-infected CHB patients, and the current studies showing higher
      than expected prevalence, it is time to call for HDV screening of all CHB
      patients. HDV viral load detection and measurement should be considered in all
      patients whether or not they are anti-HDV-positive. With universal screening of
      CHB patients for HDV, earlier diagnosis and consideration of treatment would be
      possible. Current treatment of HDV is IFN-based therapy with or without HBV
      antivirals, but current research indicates the possibility that prenylation
      inhibitors, entry inhibitors, HBsAg release inhibitors, or other therapies
      currently in the pipeline may provide more effective therapy in the future. In
      addition, universal screening would serve the important public health goal of
      allowing patients to be educated on their status and on the need for HDV-negative
      patients to protect themselves against superinfection and for HDV-infected
      patients to protect against transmission to others. Further studies and global
      awareness of HDV infection are needed. 

PMID- 24293020
TI  - Spatio-temporal measures of electrophysiological correlates for behavioral
      multisensory enhancement during visual, auditory and somatosensory stimulation: A
      behavioral and ERP study.
AB  - Multisensory enhancement, as a facilitation phenomenon, is responsible for
      superior behavioral performance when an individual is responding to cross-modal
      versus modality-specific stimuli. However, the event-related potential (ERP)
      counterparts of behavioral multisensory enhancement are not well known. We
      recorded ERPs and behavioral data from 14 healthy volunteers with three types of
      target stimuli (modality-specific, bimodal, and trimodal) to examine the spatio
      temporal electrophysiological characteristics of multisensory enhancement by
      comparing behavioral data with ERPs. We found a strong correlation between P3
      latency and behavioral performance in terms of reaction time (RT) (R = 0.98, P
      <0.001), suggesting that P3 latency constitutes a temporal measure of behavioral
      multisensory enhancement. In addition, a fast RT and short P3 latency were found
      when comparing the modality-specific visual target with the modality-specific
      auditory and somatosensory targets. Our results indicate that behavioral
      multisensory enhancement can be identified by the latency and source distribution
      of the P3 component. These findings may advance our understanding of the neuronal
      mechanisms of multisensory enhancement. 

PMID- 24293022
TI  - [Primary Prevention during Interaction of Teachers and Students--An
      Interdisciplinary Modular Programme According to Psychic and Psychosomatic
      Disorders in the Setting of Vocational Schools].
AB  - The aim of the project was the development of a modular primary preventive
      programme according to psychic and psychosomatic disorders in the setting of
      vocational schools and the evaluation of the corresponding interventions.
      Preventive strategies were integrated in the basic and further education of
      teachers and a concept for their occupational medical care. These strategies with
      long-term effects were supplemented by interventions to promote health and
      competence directly in the field. 

PMID- 24293021
TI  - NMR study of short beta(1-3)-glucans provides insights into the structure and
      interaction with Dectin-1.
AB  - beta(1-3)-Glucans, abundant in fungi, have the potential to activate the innate
      immune response against various pathogens. Although part of the action is exerted
      through the C-type lectin-like receptor Dectin-1, details of the interaction
      mechanism with respect to glucan chain-length remain unclear. In this study, we
      investigated a set of short beta(1-3)-glucans with varying degree of
      polymerization (DP); 3, 6, 7, 16, and laminarin (average DP; 25), analyzing the
      relationship between the structure and interaction with the C-type lectin-like
      domain (CTLD) of Dectin-1. The interaction of short beta(1-3)-glucans (DP6, DP16,
      and laminarin) with the CTLD of Dectin-1 was systematically analyzed by (1)H-NMR
      titration as well as by saturation transfer difference (STD)-NMR. The domain
      interacted weakly with DP6, moderately with DP16 and strongly with laminarin, the
      latter plausibly forming oligomeric protein-laminarin complexes. To obtain
      structural insights of short beta(1-3)-glucans, the exchange rates of hydroxy
      protons were analyzed by deuterium induced (13)C-NMR isotope shifts. The hydroxy
      proton at C4 of laminarin has slower exchange with the solvent than those of DP7
      and DP16, suggesting that laminarin has a secondary structure. Diffusion ordered
      spectroscopy revealed that none of the short beta(1-3)-glucans including
      laminarin forms a double or triple helix in water. Insights into the interaction
      of the short beta(1-3)-glucans with Dectin-1 CTLD provide a basis to understand
      the molecular mechanisms of beta-glucan recognition and cellular activation by
      Dectin-1. 

PMID- 24293023
TI  - [Children and Adolescents--Preventive Activities are Effective].
AB  - Health-related attitudes and behaviour are working already in the first years of
      life. Approaches of prevention for children and adolescents exist from structured
      programmes to promote healthy behaviour and to strengthen life skills through the
      support of parents to the qualification of professionals for the promotion of
      childhood resources. An essential starting point is the design of living
      conditions in which children and young people spend a lot of their time. An
      important goal of the BMBF-Forderschwerpunkt "Prevention Research" was the
      knowledge about which programmes, policies and approaches are effective and
      justify a transfer into practice. On looking back on the projects, some factors
      for the effectiveness of the measures could be identified: the presence of a
      reason, context reference, programme offerings and activation of all actors. The
      research projects also provide evidence of an increase in knowledge of effective
      evaluation since supply onset, although a binding standard of evaluation, the
      understanding of relevant outcome measures and other aspects are still lacking. 

PMID- 24293024
TI  - [Sociocultural Factors and Eating Disorders in Adolescence: Evaluation of a
      School-Based Programme].
AB  - Eating disorders are serious, hard to treat and widely spread. Hence it was the
      goal of the present project to develop and evaluate a universal preventive
      concept (Potsdam Prevention at Schools). The POPS programme focuses in an
      interactive manner on topics such as coping with social pressure, strengthening
      the media and problem-solving competence and healthy eating. Results from the ITT
      analysis support its efficacy, even over the course of one year in terms of
      reduction of body dissatisfaction, perceived media pressure, internalising of the
      media beauty ideal and disordered eating. 

PMID- 24293025
TI  - [Management of patients with the cardinal symptom dizziness or vertigo].
AB  - BACKGROUND: Vertigo and dizziness are common symptoms leading patients to consult
      a physician. The nationally representative "2003 Health Survey" depicts the
      epidemiology of the symptoms vertigo and dizziness across all of Germany. A
      breakdown of the data by region is not available. METHODS: Routine data of the
      Bavarian Association of Statutory Health Insurance Physicians accounting centre
      ("Kassenarztliche Vereinigung Bayerns", KVB) from 2008 were analysed using
      multilevel models to investigate individual and regional factors and the
      relevance of nonspecific regional heterogeneity. RESULTS: Altogether, 866,086 of
      9,269,729 (9.34%) inhabitants received an ambulatory diagnosis of vertigo or
      dizziness, including 1.77 times as many women as men. Visits to the doctor
      because of vertigo or dizziness increased with age. After adjustments for age and
      sex, a North-South divide and a higher prevalence in the urban centres were
      apparent within Bavaria. The majority of patients were seen by their GP and
      nearby doctors. This held especially true for women. Also older patients were
      less likely to go to specialists further afield. CONCLUSION: This analysis of the
      KVB data of patients with vertigo or dizziness underlines the central role that
      is played by GPs in diagnosis and treatment. In order to correctly diagnose the
      underlying causes, treat patients or send them to specialists effectively, all
      doctors need to be trained about this relevant clinical symptom. The insufficient
      representation of clinically established vertigo disorders by the ICD-10 was
      problematic. The most frequently coded diagnosis was N95.1 "postmenopausal
      dizziness".

PMID- 24293028
TI  - England's health department agrees to independent review of standardised tobacco
      packaging.

PMID- 24293026
TI  - School-associated problem behavior in childhood and adolescence and development
      of adult schizotypal symptoms: a follow-up of a clinical cohort.
AB  - How school-associated behavioral problems in childhood and adolescence precede
      distinctive adult schizotypal symptoms was examined. Gender specific findings
      were explored. After 11.6 (SD = 3.1) years, 159 patients of the Department of
      Child and Adolescent Psychiatry of the University Medical Centre Utrecht, the
      Netherlands were reassessed for adult schizotypal symptoms. Severity of
      behavioral symptoms in childhood and adolescence using Teacher Report Form (TRF;
      Verhulst et al. 1997) and adult schizotypal symptoms using Schizotypal
      Personality Questionnaire-Revised (Raine in Schizophrenia Bulletin 17:555-564,
      1991) were examined by Spearman's bivariate correlations. Multiple regression
      analyses were performed to determine the combined predictive value of significant
      TRF subscales for schizotypal symptomatology. Moderation was tested by adding the
      interactions of gender with TRF subscales to the models. Disregarding gender,
      correlational analyses revealed that TRF Total problems, in specific thought
      problems, social problems, and attentional problems were associated with
      disorganized schizotypal symptoms in adult life. TRF thought problems was also
      associated with future positive schizotypal symptoms. When gender was taken into
      account, for boys only thought problems was associated with adult positive
      schizotypal symptoms, whereas for girls externalizing problems, specifically
      attentional and aggressive problems, were associated with the higher levels of
      adult disorganized schizotypal symptoms. Moderated regression analyses provided
      trend significant evidence confirming that in girls externalizing problems were
      positively associated with general and disorganized schizotypal symptoms. When
      using teachers as informants, it was found that juvenile behavioral abnormalities
      were differentially associated with type of adult schizotypal symptoms, with
      these associations being further modified by gender. 

PMID- 24293029
TI  - Quality of life of leprosy sequelae patients living in a former leprosarium under
      home care: univariate analysis.
AB  - INTRODUCTION: Quality of life (QoL) is a broad concept that has become more
      important during the last decades. Despite this fact, few studies have been
      conducted to evaluate leprosy patients, none of which has specifically addressed
      patients with leprosy sequels submitted to home care. PURPOSE: To evaluate the
      QoL of leprosy sequel bearers and the factors that may affect their perception of
      their condition. METHODS: WHOQoL-BREF, a questionnaire developed by the World
      Health Organization, was administered to 32 people living in the coverage area of
      a former leprosarium. Patient socio-demographic and care-related caregiver data
      were collected. Activities of daily living and Instrumental Activities of Daily
      Living Scales were used to evaluate autonomy. Mini-Mental Status Examination was
      used to evaluate cognitive status. Simple linear regression analyses were
      conducted using SPSS Statistical Software and the non-standardized beta values
      were presented. RESULTS: The patients were mainly female, widowed, elderly, with
      bone sequels; all had impairment of at least one Instrumental Daily Living
      Activity. QoL scores were 12.35 in a 4-20 scale (52.18 %) in the physical domain,
      12.95 (55.94 %) in the psychological health domain, 13.18 (57.40 %) in the
      environment domain, and 16.09 (75.56 %) in the social domain. Univariate analysis
      suggests that instrumental daily activity "capacity of shopping," marital status,
      and caregiver age were associated with self-perceived QoL. Data were also
      compared to those from other studies. CONCLUSION: Individuals affected by leprosy
      had low QoL scores in the physical and psychological health domains and high
      scores in the social domain. The factors that impact their QoL seem to be related
      to specific conditions found in the leprosarium and the previous isolation
      practices.

PMID- 24293030
TI  - A framework for correcting brain retraction based on an eXtended Finite Element
      Method using a laser range scanner.
AB  - BACKGROUND: Brain retraction causes great distortion that limits the accuracy of
      an image-guided neurosurgery system that uses preoperative images. Therefore,
      brain retraction correction is an important intraoperative clinical application.
      METHODS: We used a linear elastic biomechanical model, which deforms based on the
      eXtended Finite Element Method (XFEM) within a framework for brain retraction
      correction. In particular, a laser range scanner was introduced to obtain a
      surface point cloud of the exposed surgical field including retractors inserted
      into the brain. A brain retraction surface tracking algorithm converted these
      point clouds into boundary conditions applied to XFEM modeling that drive brain
      deformation. To test the framework, we performed a brain phantom experiment
      involving the retraction of tissue. Pairs of the modified Hausdorff distance
      between Canny edges extracted from model-updated images, pre-retraction, and post
      retraction CT images were compared to evaluate the morphological alignment of our
      framework. Furthermore, the measured displacements of beads embedded in the brain
      phantom and the predicted ones were compared to evaluate numerical performance.
      RESULTS: The modified Hausdorff distance of 19 pairs of images decreased from
      1.10 to 0.76 mm. The forecast error of 23 stainless steel beads in the phantom
      was between 0 and 1.73 mm (mean 1.19 mm). The correction accuracy varied between
      52.8 and 100 % (mean 81.4 %). CONCLUSIONS: The results demonstrate that the brain
      retraction compensation can be incorporated intraoperatively into the model
      updating process in image-guided neurosurgery systems.

PMID- 24293031
TI  - A rare cause of upper gastrointestinal bleeding in an elderly patient: primary
      duodenal malignant melanoma.

PMID- 24293032
TI  - Simultaneous analysis and peroxynitrite-scavenging activity of galloylated
      flavonoid glycosides and ellagic acid in Euphorbia supina.
AB  - The herbs of Euphorbia supina (Euphorbiaceae) have been used to treat hemorrhage,
      chronic bronchitis, hepatitis, jaundice, diarrhea, gastritis, and hemorrhoids as
      a medicinal herb. This work is aimed to qualitatively and quantitatively analyze
      the polyphenols with peroxynitrite-scavenging activities. The eight compounds:
      gallic acid, methyl gallate, avicularin, astragalin, juglanin, isoquercitrin 6"
      gallate, astragalin 6"-gallate, and ellagic acid, were isolated from E. supina
      and used for HPLC analysis and peroxynitrite (ONOO(-))-scavenging assay.
      Simultaneous analysis of the eight compounds was performed on MeOH extract and
      its fractions. The contents in MeOH extract and peroxynitrite-scavenging
      activities of the dimer of gallic acid, ellagic acid (15.64 mg/g; IC50 0.89 MUM),
      and two galloylated flavonoid glycosides, astragalin 6"-gallate (13.72 mg/g; IC50
      1.43 MUM) and isoquercitrin 6"-gallate (16.99 mg/g; IC50 1.75 MUM), were high,
      compared to other compounds. The legendary uses of E. supina could be attributed
      to the high content of polyphenols, particularly ellagic acid, isoquercitrin 6"
      gallate, and astragalin 6"-gallate as active principles.

PMID- 24293033
TI  - Will artificial gametes end infertility?
AB  - In this paper we will look at the various ways in which infertility can be
      understood and at how need for reproductive therapies can be construed. We will
      do this against the background of research with artificial gametes (AGs). Having
      explored these questions we will attempt to establish the degree to which
      technologies such as AGs could expand the array of choices that people have to
      reproduce and/or become parents. Finally, we will examine whether and in what
      ways the most promising developments of such technologies are likely to bring
      about the "end of infertility". 

PMID- 24293034
TI  - Exercise intolerance in chronic heart failure: the role of cortisol and the
      catabolic state.
AB  - Chronic heart failure (CHF) is a complex clinical syndrome leading to exercise
      intolerance due to muscular fatigue and dyspnea. Hemodynamics fail to explain the
      reduced exercise capacity, while a significant skeletal muscular pathology seems
      to constitute the main underlying mechanism for exercise intolerance in CHF
      patients. There have been proposed several metabolic, neurohormonal and immune
      system abnormalities leading to an anabolic/catabolic imbalance that plays a
      central role in the pathogenesis of the wasting process of skeletal muscle
      myopathy. The impairment of the anabolic axes is associated with the severity of
      symptoms and the poor outcome in CHF, whereas increased cortisol levels are
      predictive of exercise intolerance, ventilatory inefficiency and chronotropic
      incompetence, suggesting a significant contributing mechanism to the limited
      functional status. Exercise training and device therapy could have beneficial
      effects in preventing and treating muscle wasting in CHF. However, specific
      anabolic treatment needs more investigation to prove possible beneficial effects.

PMID- 24293035
TI  - Angiotensin-converting enzyme 2 as a therapeutic target for heart failure.
AB  - The renin-angiotensin system (RAS) plays a major role in the pathophysiology of
      cardiovascular disorders. Angiotensin II (Ang-II), the final product of this
      pathway, is known for its vasoconstrictive and proliferative effects. Angiotensin
      converting enzyme 2 (ACE2), a newly discovered homolog of ACE, plays a key role
      as the central negative regulator of the RAS. It diverts the generation of
      vasoactive Ang-II into the vasodilatory and growth inhibiting peptide
      angiotensin(1-7) [Ang(1-7)], thereby providing counter-regulatory responses to
      neurohormonal activation. There is substantial experimental evidence evaluating
      the role of ACE2/Ang(1-7) in hypertension, heart failure, and atherosclerosis. In
      this review, we aim to focus on the conceptual facts of the ACE2-Ang(1-7) axis
      with regards to clinical implications and therapeutic targets in cardiovascular
      disorders, with emphasis on the potential therapeutic role in cardiovascular
      diseases. 

PMID- 24293036
TI  - Simultaneous procedures during left ventricular assist device implantation: is
      less always more?
AB  - In up to 50% of patients undergoing continuous flow, axial pump, left-ventricular
      and assist device (LVAD) placement, concomitant procedures are performed. The
      underlying lesions have a broad spectrum of severity, complexity, and impact on
      clinical outcomes. This review describes the concomitant lesions often
      encountered with LVAD implantation and clinical relevance of their repair.

PMID- 24293038
TI  - Symptom recognition to diagnosis of autism in Nepal.
AB  - Awareness and knowledge about autism is almost non-existent in Nepal. Children
      who eventually get the diagnosis often miss their opportunity for early
      intervention. The current study shows that medical help was seeked at mean age of
      27.9 + 14.5 months and most of them were for delayed language and the first
      preference for parents were pediatricians. The mean age of diagnosis of autism
      was 55.6 months. The time length between help seeking to diagnosis was 29.4
      months with longest time lag of 13 years. Delay in recognition of symptoms, delay
      in health seeking and lack of awareness even in treating physicians might be the
      reason for advanced age at diagnosis of autism in Nepal. 

PMID- 24293039
TI  - Symbolic understanding of pictures in low-functioning children with autism: the
      effects of iconicity and naming.
AB  - This research investigated whether symbolic understanding of pictures in low
      functioning children with autism is mediated by iconicity and language. In
      Experiment 1, participants were taught novel words paired with unfamiliar
      pictures that varied in iconicity (black-and-white line drawings, greyscale
      photographs, colour line drawings, colour photographs). Unlike mental-age matched
      typically developing peers, children with autism generally mapped words onto
      pictures rather than depicted referents, however, they generalised labels more
      frequently in colour picture conditions. In Experiment 2, children with autism
      categorised a line drawing with its referent, rather than another picture,
      regardless of whether it was named. Typically developing children only viewed
      pictures as symbols when they were labelled. Overall, symbolic understanding of
      pictures in children with autism is facilitated by iconicity (particularly
      colour), but not language. 

PMID- 24293040
TI  - Rigid-compulsive behaviors are associated with mixed bowel symptoms in autism
      spectrum disorder.
AB  - Based on clinical experience, we hypothesized that rigid-compulsive behaviors are
      associated with severe constipation and co-occurring diarrhea or underwear
      staining in children with autism spectrum disorder. Using data from the Autism
      Treatment Network, we evaluated the association between these gastrointestinal
      symptoms and measures of rigid compulsive behavior in children ages 2-17.
      Following statistical correction, four of five primary measures were
      significantly associated with constipation and diarrhea or underwear staining,
      including parental report of repetitive behavior, parental report of compulsive
      behavior, clinician diagnosis of obsessive-compulsive disorder, and report of
      rituals observed on the autism diagnostic observation schedule. This association
      could point to a causal connection between these symptoms or to a common
      biological pathway that impacts both gut and brain. 

PMID- 24293041
TI  - Epicardial adipose tissue: relationship between measurement location and
      metabolic syndrome.
AB  - Epicardial adipose tissue (EAT) is a contributing factor of metabolic syndrome
      (MS) and coronary artery disease (CAD). However, it is still unclear which
      measurement location of EAT area best reflects its cardiometabolic risk. The
      purpose of our study was to investigate the distribution of EAT and its
      relationship to the total EAT volume and MS. To assess volume and cross-sectional
      areas of EAT, coronary CT angiography were obtained in 256 asymptomatic subjects.
      The EAT areas within the threshold range of -190 to -30 Hounsfield units were
      measured at six representative slices. Correlations between single slice EAT
      areas and total EAT volumes were high across all measurement locations
      (correlation coefficient r > 0.80). The receiver-operator characteristic curves
      demonstrated EAT area at left main coronary artery (LMCA) was well discriminative
      for MS (AUC 0.82, p < 0.001) and CAD (AUC 0.76, p < 0.001). EAT areas across all
      measurement locations were significantly increased linearly with increasing
      number of MS components. EAT areas were significantly associated with MS at all
      measurement locations; the highest odds ratio (OR) between EAT area and MS was at
      the LMCA level (OR 5.86, p < 0.001). The OR between EAT area and coronary artery
      calcium was also significant in LMCA locations (OR 1.56, p = 0.042). We
      demonstrated that the single-slice EAT area measurement is a simple and reliable
      method compared with time-consuming volumetric measurements. The EAT area at LMCA
      level was the best single slice representing the risk of metabolic syndrome and
      coronary atherosclerosis.

PMID- 24293042
TI  - Comparison of characteristic CT findings of lymphedema, cellulitis, and
      generalized edema in lower leg swelling.
AB  - To determine the different computed tomography (CT) findings of lymphedema,
      cellulitis, and generalized edema in the lower leg. CT images of 44 patients with
      confirmed lymphedema (n = 19), cellulitis (n = 11), or generalized edema (n = 14)
      were retrospectively reviewed. The following characteristics were evaluated:
      extent of edema, laterality, skin thickening, honeycombing, taller than wide
      appearance, muscle edema, conglomeration of septum of fat lobule, fluid
      collection, fascial enhancement, inguinal lymph node (LN) enlargement, medullary
      fat obliteration of inguinal LN, trunk subcutaneous edema, and bone marrow edema.
      Fisher's exact test with Bonferroni correction was used for multiple comparisons.
      Honeycombing and taller than wide appearance of fat lobules were more common in
      lymphedema (P < 0.01). Fat obliteration of inguinal LN and inguinal LN
      enlargement at the affected side were more common in cellulitis (P < 0.01). Bone
      marrow and subcutaneous edema of the trunk were more common in generalized edema
      (P < 0.01). Honeycombing is commonly seen in lymphedema, but is not a specific
      finding. Inguinal LN enlargement is a specific sign of cellulitis. Truncal edema
      and bone marrow edema were specific findings of generalized edema.

PMID- 24293043
TI  - Quantification of coronary artery plaque using 64-slice dual-source CT:
      comparison of semi-automatic and automatic computer-aided analysis based on
      intravascular ultrasonography as the gold standard.
AB  - We evaluated the feasibility of automatic computer-aided analysis (CAA) compared
      with semi-automatic CAA for differentiating lipid-rich from fibrous plaques based
      on coronary CT angiography (CCTA) imaging. Seventy-four coronary plaques in 57
      patients were evaluated by CCTA using 64-slice dual-source CT. Quantitative
      analysis of coronary artery plaques was performed by measuring the relative
      volumes (low, medium, and calcified) of plaque components using automatic CAA and
      by measuring mean CT density using semi-automatic CAA. We compared the two plaque
      measurement methods for lipid-rich and fibrous plaques using Pearson's
      correlation. Intravascular ultrasonography was used as the goal standard for
      assessment of plaques. Mean CT density of plaques tended to increase in the order
      of lipid [36 +/- 19 Hounsfield unit (HU)], fibrous (106 +/- 34 HU), and then
      calcified plaques (882 +/- 296 HU). The mean relative volumes of 'low' components
      measured by automatic CAA were 13.8 +/- 4.6, 7.9 +/- 6.7, and 3.5 +/- 3.0 % for
      lipid, fibrous, and calcified plaques, respectively (r = -0.348, P = 0.022). The
      mean relative volumes of 'medium' components on automatic CAA were 12.9 +/- 4.1,
      15.7 +/- 9.6, and 5.6 +/- 4.8 % for lipid, fibrous, and calcified plaques,
      respectively (r = -0.385, P = 0.011). The mean relative volumes of low and medium
      components within plaques significantly correlated with the types of plaques.
      Plaque analysis using automatic CAA has the potential to differentiate lipid from
      fibrous plaques based on measurement of the relative volume percentages of the
      low and medium components.

PMID- 24293044
TI  - Coronary CTA appearance of anomalous left coronary artery arising from the
      pulmonary artery with intramural aortic route.
AB  - Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare
      anomaly in which the left main coronary artery (LM) typically arises from the
      left infero-lateral aspect of the main pulmonary artery just above the pulmonary
      valve. This case report presents a case of variant ALCAPA where the LM arises
      from the supero-medial aspect of the distal pulmonary artery, taking an unusual
      course within the wall of the aorta: ALCAPA with Intramural Aortic Route (ALCAPA
      IAR). Both Coronary artery Computed Tomographic Angiography (CCTA) and digital
      subtraction angiography were used to image the patient prior to surgical
      intervention. ALCAPA-IAR was confirmed and repaired in the operating room. While
      this variant has been described in the literature, the appearance on CCTA has not
      yet been described. Recognizing this variant on preoperative imaging is vitally
      important as it can affect the surgical approach. 

PMID- 24293045
TI  - Cardiac computed tomography angiography results in diagnostic and therapeutic
      change in prosthetic heart valve endocarditis.
AB  - Echocardiography may miss prosthetic heart valve (PHV) endocarditis which
      advocates for novel imaging techniques to improve diagnostic accuracy and patient
      outcome. The purpose of this study was to determine the complementary diagnostic
      value of cardiac computed tomography angiography (CTA) to the clinical routine
      workup including transthoracic and transesophageal echocardiography (TTE/TEE) in
      patients with suspected PHV endocarditis and its impact on patient treatment. A
      diagnostic prospective cross-sectional study was chosen as design. Besides
      clinical routine workup (including TTE/TEE), CTA was performed to assess its
      diagnostic accuracy and complementary diagnostic/therapeutic value. For the
      diagnostic accuracy, the reference standard was surgical findings or clinical
      follow-up. To determine the complementary diagnostic/therapeutic value an expert
      panel was used as reference standard. Twenty-eight patients were included. CTA
      resulted in a major diagnostic change in six patients (21 %) mainly driven by
      novel detection of mycotic aneurysms by CTA. Furthermore, treatment changes
      occurred in seven patients (25 %) compared to clinical routine workup. Diagnostic
      accuracy of routine clinical workup plus CTA was superior to clinical routine
      workup alone for the detection of PHV endocarditis in general, vegetations and
      peri-annular extension. This study demonstrates that CTA and clinical workup
      including TTE and TEE are complementary in patients with PHV endocarditis.
      Therefore, CTA imaging has to be considered after clinical routine workup in
      patients with a high suspicion on PHV endocarditis.

PMID- 24293046
TI  - Type B aortic interruption in an adult.
AB  - A 19-year-old male presented with mild to moderate hypertension and differential
      cyanosis. Transthoracic echocardiography and multi-slice computed tomography
      revealed type B aortic interruption along with various congenital cardiac defects
      including patent ductus arteriosus with bidirectional shunt, perimembranous
      ventricular septal defect with left-to-right shunt, bicuspid aortic valve, and
      severe pulmonary hypertension. 

PMID- 24293047
TI  - Correlates of left ventricular mass in chronic hemodialysis recipients.
AB  - We aimed to clarify the correlates of left ventricular mass and secondarily, left
      ventricular volume, in a cohort of prevalent hemodialysis recipients. Left
      ventricular hypertrophy is common and left ventricular mass is a widely-accepted
      surrogate for clinical outcomes in dialysis recipients, who are often subjected
      to chronic pressure and volume overload. However, the precise pathophysiologic
      mechanisms of left ventricular hypertrophy in this unique population have not
      been well understood. This was a cross-sectional study of patients receiving
      conventional thrice-weekly dialysis in Toronto, Canada. Left ventricular mass and
      volume were assessed with cardiac magnetic resonance and indexed to the patient's
      height to the power of 2.7. Fibroblast growth factor-23 concentration was
      measured using a C-terminal enzyme-linked immunosorbent assay. Patient
      demographics, comorbidities, dialysis-associated blood pressures and
      ultrafiltration volumes, biochemical and hematologic parameters, vascular access
      and medications were extracted from clinical records. Multivariable linear
      regression was used to identify independent correlates of left ventricular mass
      index (LVMI) and the left ventricular end diastolic volume index (LVEDVI). We
      enrolled 56 patients, of whom 23 (41.1 %) were women with mean age 54 +/- 12
      years. Mean LVMI was 31.1 +/- 6.8 g/m(2.7). In multivariable analyses, systolic
      blood pressure and LVEDVI were the only factors significantly associated with
      LVMI. Post-dialysis weight, percent reduction in urea and the presence of a
      permanent form of vascular access were associated with LVEDVI. Fibroblast growth
      factor-23 was not associated with either LVMI or LVEDVI. Blood pressure and left
      ventricular dilatation are independent determinants of elevated left ventricular
      mass. Aggressive blood pressure reduction and avoidance of volume overload may
      confer LVM regression and improve clinical outcomes.

PMID- 24293049
TI  - Major and minor neurocognitive disorders in DSM-5: the difference between the map
      and the terrain.

PMID- 24293048
TI  - The role of F18-fluorodeoxyglucose positron emission tomography in identifying
      patients at high risk for lethal arrhythmias from cardiac sarcoidosis and the use
      of serial scanning to guide therapy.
AB  - Substantial literature exists linking inflammation with arrhythmia, in particular
      with regards to serological markers of systemic inflammation. Regional
      inflammation can be identified using positron emission tomography (PET) with the
      radiotracer F18-fluorodeoxyglucose (F18-FDG). In the current series, we
      demonstrate novel applications of cardiac PET using F18-FDG and N13-ammonia
      radiotracers in the evaluation and treatment of arrhythmia associated with
      cardiac sarcoidosis. These applications include defining the cause of arrhythmia,
      identifying arrhythmias that will be amenable to medical management, and guiding
      therapy using serial scanning. Though these applications are promising,
      prospective multicenter studies are needed to provide better understanding of the
      utility of PET imaging in the diagnosis and treatment of arrhythmias. 

PMID- 24293050
TI  - Are we over-diagnosing autism? The case against.

PMID- 24293051
TI  - The autism spectrum disorder 'epidemic': need for biopsychosocial formulation.

PMID- 24293052
TI  - Should we deplore the disappearance of hypochondriasis from DSM-5?

PMID- 24293053
TI  - The poetics of therapeutic practice: motivational interviewing and the powers of
      pause.
AB  - Motivational interviewing (MI) is an increasingly prominent behavioral therapy
      that draws from and claims to synthesize two American therapeutic traditions long
      thought to be antithetical-"client-centered" and "directive" approaches. This
      paper proposes that MI achieves its hallmark "client-centered directiveness"
      through the aesthetic management of the therapeutic encounter, and more
      particularly, through MI practitioners' marked use of silence. Drawing on data
      collected during the ethnographic study of MI trainings and the formal analysis
      of video-recorded MI sessions that are commonly used as models in such trainings,
      we identify three patterns of pause that regularly fall at specific grammatical
      junctures within seasoned MI practitioners' turns-at-talk. We demonstrate how
      these pauses allow MI practitioners to subtly direct the conversation while
      simultaneously displaying unequivocal signs of client-centeredness. In other
      words, we show how and explain why the poetics of pause matter to MI. In
      presenting this case, we more generally highlight practice poetics-that is, the
      aesthetic management of the style and delivery of a professional message with a
      particular practical aim in mind-suggesting that this is a central if under
      appreciated aspect of therapeutic practices. 

PMID- 24293054
TI  - Ethical standards in sport and exercise science research: 2014 update..

PMID- 24293055
TI  - Validation of the CORB75 (confusion, oxygen saturation, respiratory rate, blood
      pressure, and age >= 75 years) as a simpler pneumonia severity rule.
AB  - PURPOSE: This study compares the ability of two simpler severity rules (classical
      CRB65 vs. proposed CORB75) in predicting short-term mortality in elderly patients
      with community-acquired pneumonia (CAP). METHODS: A population-based study was
      undertaken involving 610 patients >= 65 years old with radiographically confirmed
      CAP diagnosed between 2008 and 2011 in Tarragona, Spain (350 cases in the
      derivation cohort, 260 cases in the validation cohort). Severity rules were
      calculated at the time of diagnosis, and 30-day mortality was considered as the
      dependent variable. The area under the receiver operating characteristic curves
      (AUC) was used to compare the discriminative power of the severity rules.
      RESULTS: Eighty deaths (46 in the derivation and 34 in the validation cohorts)
      were observed, which gives a mortality rate of 13.1 % (15.6 % for hospitalized
      and 3.3 % for outpatient cases). After multivariable analyses, besides CRB
      (confusion, respiration rate >= 30/min, systolic blood pressure <90 mmHg or
      diastolic <= 60 mmHg), peripheral oxygen saturation (<= 90 %) and age >= 75 years
      appeared to be associated with increasing 30-day mortality in the derivation
      cohort. The model showed adequate calibration for the derivation and validation
      cohorts. A modified CORB75 scoring system (similar to the classical CRB65, but
      adding oxygen saturation and increasing the age to 75 years) was constructed. The
      AUC statistics for predicting mortality in the derivation and validation cohorts
      were 0.79 and 0.82, respectively. In the derivation cohort, a CORB75 score >= 2
      showed 78.3 % sensitivity and 65.5 % specificity for mortality (in the validation
      cohort, these were 82.4 and 71.7 %, respectively). CONCLUSIONS: The proposed
      CORB75 scoring system has good discriminative power in predicting short-term
      mortality among elderly people with CAP, which supports its use for severity
      assessment of these patients in primary care.

PMID- 24293056
TI  - A phase I open-label study to investigate the potential drug-drug interaction
      between single-dose dacomitinib and steady-state paroxetine in healthy
      volunteers.
AB  - Dacomitinib is currently in development for the treatment of non-small cell lung
      cancer. Formation of the major circulating metabolite (PF-05199265) is mediated
      by cytochrome P450 (CYP) 2D6 and CYP2C9. This phase I, single fixed-sequence, two
      period study evaluated the effect of paroxetine, a CYP2D6 inactivator, on
      dacomitinib pharmacokinetics in healthy volunteers who were extensive CYP2D6
      metabolizers. Subjects received a single 45-mg dacomitinib dose alone and in
      combination with paroxetine (30 mg/day for 10 consecutive days, with dacomitinib
      administered on day 4) at steady-state levels. Blood samples were collected
      through 240 hours post-dacomitinib dosing. Dacomitinib exposure (area under the
      concentration-time curve from 0 to infinity; AUCinf) increased 37%; however a
      reduction in PF-05199265 AUCinf of approximately 90% was observed during the
      paroxetine treatment period. The maximum concentration of dacomitinib changed
      minimally. Adverse events reported with single-dose dacomitinib administered
      alone or in the presence of steady-state levels of paroxetine were mostly mild,
      and no serious adverse events were reported. While paroxetine significantly
      inhibited CYP2D6-mediated metabolism of a single dose of dacomitinib, the modest
      effect on dacomitinib exposure is unlikely to be clinically relevant when
      dacomitinib is given daily. Dose adjustment of dacomitinib may therefore not be
      required upon coadministration with a CYP2D6 inhibitor. 

PMID- 24293057
TI  - A new mixed-mode model for interpreting and predicting protein elution during
      isoelectric chromatofocusing.
AB  - Experimental data are combined with classic theories describing electrolytes in
      solution and at surfaces to define the primary mechanisms influencing protein
      retention and elution during isoelectric chromatofocusing (ICF) of proteins and
      protein mixtures. Those fundamental findings are used to derive a new model to
      understand and predict elution times of proteins during ICF. The model uses a
      modified form of the steric mass action (SMA) isotherm to account for both ion
      exchange and isoelectric focusing contributions to protein partitioning. The
      dependence of partitioning on pH is accounted for through the characteristic
      charge parameter m of the SMA isotherm and the application of Gouy-Chapman theory
      to define the dependence of the equilibrium binding constant Kbi on both m and
      ionic strength. Finally, the effects of changes in matrix surface pH on protein
      retention are quantified through a Donnan equilibrium type model. By accounting
      for isoelectric focusing, ion binding and exchange, and surface pH contributions
      to protein retention and elution, the model is shown to accurately capture the
      dependence of protein elution times on column operating conditions.

PMID- 24293058
TI  - Pharmaceutical pricing in emerging markets: effects of income, competition, and
      procurement.
AB  - This paper analyzes determinants of ex-manufacturer prices for originator and
      generic drugs across countries. We focus on drugs to treat HIV/AIDS, TB, and
      malaria in middle and low-income countries (MLICs), with robustness checks to
      other therapeutic categories and the full income range of countries. We examine
      the effects of per capita income, income dispersion, competition from originator
      and generic substitutes, and whether the drugs are sold to retail pharmacies
      versus tendered procurement by non-government organizations. The cross-national
      income elasticity of prices is 0.27 across the full income range of countries but
      is 0.0-0.10 between MLICs, implying that drugs are least affordable relative to
      income in the lowest income countries. Within-country income inequality
      contributes to relatively high prices in MLICs. Although generics are priced
      roughly 30% lower than originators on average, the variance is large. Additional
      generic competitors only weakly affect prices, plausibly because generic quality
      uncertainty leads to competition on brand rather than price. Tendered procurement
      that imposes quality standards attracts multinational generic suppliers and
      significantly reduces prices of originator and generic drugs, compared with their
      respective prices to retail pharmacies.

PMID- 24293059
TI  - Quality of life and related factors: a questionnaire survey of older people
      living alone in Mainland China.
AB  - PURPOSE: There is a growing population of older people living alone within the
      context of dramatic population ageing and changing living arrangements. However,
      little is known about the quality of life (QoL) of older people living alone in
      Mainland China. This study aimed to investigate QoL and its related factors among
      Chinese older people who live alone. METHODS: A stratified random cluster sample
      of 521 community-dwelling older people living alone in Shanghai completed a
      structured questionnaire through face-to-face interviews. QoL was measured using
      the Older People's Quality of Life Questionnaire. Other data collected included
      self-rated health, physical health, cognitive function, depression, functional
      ability, loneliness, social support, physical activity, health services
      satisfaction, satisfaction with overall dwelling conditions and socio-demographic
      variables. RESULTS: Older people living alone in Mainland China rated social
      relationships and financial circumstances as sources of low satisfaction within
      their QoL. Multiway analysis of variance showed that satisfaction with overall
      dwelling conditions, self-rated health, functional ability, depression, economic
      level, social support, loneliness, previous occupation and health services
      satisfaction were independently related to QoL, accounting for 68.8% of the
      variance. Depression and previous occupation had an interaction effect upon QoL.
      CONCLUSIONS: This study identified nine factors influencing the QoL of older
      people living alone in Mainland China. Interventions to increase satisfaction
      with dwelling conditions, improve economic level, social support and functional
      ability, decrease loneliness and depression and improve health services
      satisfaction appear to be important for enhancing their QoL.

PMID- 24293060
TI  - A novel missense mutation in AFG3L2 associated with late onset and slow
      progression of spinocerebellar ataxia type 28.
AB  - SCA28 is caused by mutations in the AFG3L2 gene. This gene encodes a subunit of
      the mitochondrial metalloprotease AFG3L2 (AFG3-like protein 2). Clinical features
      of SCA28 include slow to moderate progressive ataxia, dysarthria, and additional
      symptoms such as nystagmus, slow saccades, and increased deep tendon reflexes.
      Here, we report on a novel AFG3L2 mutation in a patient with slowly progressive
      ataxia and a positive family history. The nucleotide change results in the
      substitution of an evolutionarily highly conserved tyrosine by histidine
      (p.Y689H) in the M41 peptidase domain of AFG3L2. 

PMID- 24293061
TI  - Optimization of ultrasonic-assisted extraction of continentalic acid from the
      root of Aralia continentalis by using the response surface methodology.
AB  - In order to optimize the extraction conditions of continentalic acid, the main
      compound from Aralia continentalis root, we developed a model using the response
      surface methodology. The continentalic acid yield was analyzed and quantified by
      high-performance liquid chromatography coupled with UV detection. The extraction
      solvent, temperature, and time the three main factors for ultrasound-assisted
      extraction were optimized using the central composite design. Analysis of
      variance showed a good model fit (R (2) = 0.9323). The maximum extraction of
      continentalic acid obtained experimentally was 1.0138 % under an extraction
      temperature of 33  degrees C and extraction time of 28 min when 100 % ethanol was
      used as the solvent. The experimental value was in good agreement (the yield
      1.0103 %) with those predicted values. The results clearly showed that quality by
      statistical design could be effectively applied to optimize extraction of
      continentalic acid.

PMID- 24293062
TI  - Three new diphenylpropanes from Celastrus hindsii.
AB  - Three new diphenylpropanes, Hindsiipropane A-C (1-3), together with one known
      arylpropyl quinone Griffithane D (4), were isolated from Celastrus hindsii. Their
      structures were established by 1D and 2D nuclear magnetic resonance spectroscopic
      analysis, and mass spectroscopy. Compound 4 was firstly obtained in this genus.
      All the isolated compounds were evaluated in vitro for cytotoxicity against four
      human tumor cell lines (A549, HCT116, MDA-MB-231, BEL7404) by the MTT assay.

PMID- 24293063
TI  - Latest status of the clinical and industrial applications of cell sheet
      engineering and regenerative medicine.
AB  - Cell sheet engineering, which allows tissue engineering to be realized without
      the use of biodegradable scaffolds as an original approach, using a temperature
      responsive intelligent surface, has been applied in regenerative medicine for
      various tissues, and a number of clinical studies have been already performed for
      life-threatening diseases. By using the results and findings obtained from the
      initial clinical studies, additional investigative clinical studies in several
      tissues with cell sheet engineering are currently in preparation stage. For
      treating many patients effectively by cell sheet engineering, an automated system
      integrating cell culture, cell-sheet fabrication, and layering is essential, and
      the system should include an advanced three-dimensional suspension cell culture
      system and an in vitro bioreactor system to scale up the production of cultured
      cells and fabricate thicker vascularized tissues. In this paper, cell sheet
      engineering, its clinical application, and further the authors' challenge to
      develop innovative cell culture systems under newly legislated regulatory
      platform in Japan are summarized and discussed. 

PMID- 24293065
TI  - Accelerated wound healing and anti-inflammatory effects of physically cross
      linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic
      rats.
AB  - Diabetes is one of the leading causes of impaired wound healing. The objective of
      this study was to develop a bee venom-loaded wound dressing with an enhanced
      healing and anti-inflammatory effects to be examined in diabetic rats. Different
      preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based
      wound dressing containing bee venom (BV) were developed using freeze-thawing
      method. The mechanical properties such as gel fraction, swelling ratio, tensile
      strength, percentage of elongation and surface pH were determined. The
      pharmacological activities including wound healing and anti-inflammatory effects
      in addition to primary skin irritation and microbial penetration tests were
      evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in
      the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed
      of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than
      other formulations. Pharmacologically, the bee venom-loaded wound dressing that
      has the same previous composition showed accelerated healing of wounds made in
      diabetic rats compared to the control. Moreover, this bee venom-loaded wound
      dressing exhibited anti-inflammatory effect that is comparable to that of
      diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound
      tissues covered with this preparation displayed higher hydroxyproline and
      glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom
      loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound
      dressing with excellent forming and enhanced wound healing as well as anti
      inflammatory activities.

PMID- 24293064
TI  - New anti-inflammatory flavonoids from Cadaba glandulosa Forssk.
AB  - Three new flavonoids; kaempferol-4'-phenoxy-3,3',5'-trimethylether (3),
      rhamnocitrin-4'-(4-hydroxy-3-methoxy)phenoxy-3-methyl ether (4), and rhamnocitrin
      3-O-neohesperoside-4'-O-rhamnoside (6), along with three known compounds; 4
      methoxy-benzyldehyde (1), kaempferol-3-methylether (2), and stachydrine (5) were
      isolated from the aerial parts of Cadaba glandulosa Forssk. Their chemical
      structures were established by physical, chemical, and spectral methods, as well
      as comparison with literature data. The antioxidant and anti-inflammatory
      activities of the isolated compounds were determined. Compounds 2-4, and 6
      exhibited potent anti-inflammatory activity comparable with indomethacin and
      moderate antioxidant activity. 

PMID- 24293066
TI  - A new age of regenerative medicine: fusion of tissue engineering and stem cell
      research.

PMID- 24293067
TI  - Down-regulation of collagen synthesis and matrix metalloproteinase expression in
      myofibroblasts from Dupuytren nodule using adenovirus-mediated relaxin gene
      therapy.
AB  - Dupuytren's disease is a fibroproliferative connective tissue disorder
      characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a
      multifunctional factor which contributes to the remodeling of the pelvic ligament
      by inhibiting fibrosis and inflammatory activities. The aim of this study was to
      investigate the effect of the RLN gene on the inhibition of fibrosis in
      myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a
      marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene
      expressions in beta-galactosidase assay and Western blot analysis.
      Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in
      collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70%
      decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein
      expression compared with cultures with viral control and saline control. In
      addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a
      15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral
      control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a
      74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at
      48 h compared with cultures with viral control and saline control. In conclusion,
      the RLN gene render antifibrogenic effect on myofibroblastic cells from
      Dupuytren's nodule via direct inhibition of collagen synthesis not through
      collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can
      be an alternative therapeutic strategy in initial stage of Dupuytren's disease by
      its antifibrogenic effect.

PMID- 24293068
TI  - Removal of nitrogen from MBT residues by leachate recirculation in combination
      with intermittent aeration.
AB  - Mechanical-biological treatment (MBT) techniques have been used to reduce the
      emission potential of waste before placement in landfills for a couple of years,
      especially in Europe. The main focus of MBT is on the reduction of native organic
      substances and not on nitrogen compounds. As a result, the concentrations of
      organic substances in leachate from MBT landfills are considerably reduced in
      comparison to leachates from municipal solid waste landfills, while the ammonia
      nitrogen concentrations remain at a high level. From the stabilization of old
      landfills it is well known that recirculation of leachate and supplementary
      aeration can reduce emissions to an acceptable level in a comparatively short
      time. In a series of laboratory-scale tests the efficiency of this technique for
      MBT residues was investigated under different boundary conditions. While the
      effect of leachate recirculation is also well known for MBT residues, the
      additional aeration has so far not been investigated. The results show that this
      technique has only a limited influence on the reduction of organic carbon
      compounds. In view of nitrogen compounds, only the additional aeration during
      recirculation shows a strong effect on the quality of leachate, in which the
      concentrations of ammonium and total nitrogen are reduced by more than 90%. The
      results indicate that by using simple techniques the long-term emission behavior
      of MBT residues can be quickly reduced to an acceptable level. 

PMID- 24293069
TI  - Life cycle assessment of manure management and nutrient recycling from a Chinese
      pig farm.
AB  - Driven by the growing numbers of intensified pig farms around cities in China,
      there are problems of nutrient surplus and shortage of arable land for utilising
      the manure. Hence, sustainable livestock systems with effective manure management
      are needed. The objective of this study is to compare the existing manure
      treatment of a typical pig farm in Beijing area (separate collection of faeces;
      'Gan qing fen' system) with an alternative system and to identify the nutrients
      flow of the whole farm in order to quantify environmental burdens and to estimate
      the arable land required for sustainable nutrients recycling. Life cycle
      assessment is used for this purpose. Acidification potential (AP), eutrophication
      potential (EP) and global warming potential (GWP) are analysed in detail; the
      functional unit is the annual production of the pig farm. The results show that
      the cropland area demand for sustainable land application of the effluent can be
      reduced from 238 to 139 ha with the alternative system. It is possible to
      transfer 29% of total nitrogen, 87% of phosphorus, 34% of potassium and 75% of
      magnesium to the compost, and to reduce the total AP, EP and GWP of manure
      management on the farm by 64.1%, 96.7% and 22%, respectively, compared with the
      current system. Besides an effective manure management system, a full inventory
      of the regional nutrients flow is needed for sustainable development of livestock
      systems around big cities in China. 

PMID- 24293070
TI  - Under-utilisation of organic wastes during brownfield regeneration to community
      woodland: tackling the barriers.
AB  - The regeneration of brownfield land to greenspace is a governmental policy
      objective of many European countries. Healthy vegetation establishment and growth
      is an essential component of successful greenspace establishment, and research
      has shown that a planting medium of an appropriate standard for supporting
      vegetation can be created through amendment of soil-forming materials with
      organic wastes. However, failed regeneration projects suggest that barriers may
      exist that prevent the use of suitable quality soil materials. The aim of this
      research was to identify barriers to the use of organic wastes for improving soil
      materials for brownfield regeneration to community woodland. We conducted
      interviews with a range of professionals experienced in regeneration to
      greenspace, and used content analysis on interview transcripts. A diverse set of
      barriers was revealed, including a low technical awareness among some
      professional groups of how to improve soil quality, coupled with a low awareness
      of the published technical guidance. Other barriers include regulatory and
      project management issues, which influence the timings and economics of raising
      brownfield soil quality. We highlight areas in which future efforts may be
      focused to improve the quality of planting media used in land regeneration. Such
      effort will improve the sustainability of greenspaces created and complement
      effective management of organic waste streams. 

PMID- 24293071
TI  - Peribronchovascular haze: a frequently observed finding on chest X-rays in the
      acute phase of Kawasaki disease.
AB  - PURPOSE: To evaluate the frequency of peribronchovascular haze on chest X-rays
      (CXR) in patients with Kawasaki disease (KD), a finding not previously
      emphasized, and to contrast this finding with clinical, laboratory and
      echocardiographic findings. METHODS: Sixty-nine patients diagnosed as KD from
      January 2010 to December 2011 were eligible for this study. The initial CXRs were
      retrospectively reviewed by two radiologists for the presence of
      peribronchovascular haze and related findings. Echocardiography was reviewed by
      one pediatrician for the presence of coronary artery abnormalities. The follow up
      CXRs and post-remission echocardiograms were also reviewed. Patients' medical
      records were reviewed for clinical findings. Correlation between CXR findings and
      clinical findings were assessed. RESULTS: On the initial CXR, peribronchovascular
      haze was observed in 57/69 patients (82.6 %). Twenty-nine out of 69 patients
      showed abnormalities on echocardiogram (42.0 %). In the follow-up studies, CXR
      findings were improved in 25/29 patients (86.2 %). The frequencies of five
      principal clinical features of KD were from 55.1 to 88.4 %. There was no
      statistically significant correlation between the CXR finding and clinical
      findings. CONCLUSION: Peribronchovascular haze on CXR was observed in the acute
      phase of KD as frequently as the principal clinical features of KD, and more
      frequently than echocardiographic abnormalities.

PMID- 24293072
TI  - Treatment of two cases with refractory, metastatic intermediate-risk
      neuroblastoma with isotretenoin alone or observation.
AB  - Patients <12 months with favorable biology, metastatic neuroblastoma have >90%
      overall survival following treatment with chemotherapy and surgery. We report two
      infants with favorable biology, stage 4 neuroblastoma with refractory disease
      after standard intermediate-risk chemotherapy and additional retrieval
      chemotherapy. One patient was treated with six additional cycles of isotretinoin
      and the other observed. Both remain clinically well with persistent disease but
      no evidence of tumor progression for 28 and 13 months following completion of
      cytotoxic treatment. Similar to residual tumor in primary sites, refractory
      metastatic disease may not portend a poor outcome in patients with favorable
      biology, intermediate-risk neuroblastoma.

PMID- 24293073
TI  - Publishers should offer subscription discounts to universities that pay author
      fees, government agrees.

PMID- 24293074
TI  - Palliative treatment of metastatic colorectal cancer: what is the optimal
      approach?
AB  - Worldwide, colorectal cancer (CRC) is responsible for over 600,000 deaths
      annually and remains a significant public health concern. Because of therapeutic
      advancements over the past two decades, patients with metastatic CRC are living
      longer with an improved quality of life. This review will highlight recent trial
      evidence that improves outcomes for patients with metastatic disease. Topics will
      include the optimal use of first-line combination chemotherapy, bevacizumab in
      patients with advanced age or comorbidities, maintenance chemotherapy, first-line
      use of anti-EGFR therapies, first-line cetuximab versus bevacizumab, anti
      angiogenic therapies past progression, and management of treatment-refractory
      disease. Clinical trial evidence will be presented, along with guidance on how to
      integrate recent evidence into clinical practice. Finally, this review will
      examine innovative drug development strategies, and will discuss potentially
      actionable targets identified by molecular testing. 

PMID- 24293075
TI  - African American and Latino low income families' food shopping behaviors:
      promoting fruit and vegetable consumption and use of alternative healthy food
      options.
AB  - Minority families often reside in neighborhoods with few supermarkets or
      alternative healthy food options (e.g., farmers markets, community gardens),
      making fresh produce difficult to obtain. This qualitative study identified
      factors influencing fruit and vegetable shopping and use of alternative healthy
      food options. Forty-eight minority women with children completed interviews
      regarding food shopping habits and use of and attitudes toward alternative
      healthy food options. Interviews were subjected to thematic analysis. Produce
      shopping was motivated by costs and family preferences. For African American
      women, poor cooking skills restricted the variety of fruits and vegetables
      purchased. Latinas were receptive to alternative healthy food options, but did
      not use them because these sources were inconvenient. African American women were
      not receptive to them. Improving cooking skills and perceptions of acceptable
      foods may be as important as increased access to promote greater consumption of
      fruits and vegetables. 

PMID- 24293077
TI  - Optimal distribution of medical backpacks and health surveillance assistants in
      Malawi.
AB  - Despite recent progress, Malawi continues to perform poorly on key health
      indicators such as child mortality and life expectancy. These problems are
      exacerbated by a severe lack of access to health care. Health Surveillance
      Assistants (HSAs) help bridge this gap by providing community-level access to
      basic health care services. However, the success of these HSAs is limited by a
      lack of supplies and long distances between HSAs and patients. To address this
      issue, we used large-scale weighted p-median and capacitated facility location
      problems to create a scalable, three-tiered plan for optimal allocation of HSAs,
      HSA designated medical backpacks, and backpack resupply centers. Our analysis
      uses real data on the location and characteristics of hospitals, health centers,
      and the general population. In addition to offering specific recommendations for
      HSA, backpack, and resupply center locations, it provides general insights into
      the scope of the proposed HSA backpack program scale-up. In particular, it
      demonstrates the importance of local health centers to the resupply network. The
      proposed assignments are robust to changes in the underlying population
      structure, and could significantly improve access to medical supplies for both
      HSAs and patients. 

PMID- 24293076
TI  - Low level of efavirenz in HIV-1-infected Thai adults is associated with the
      CYP2B6 polymorphism.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infections with a plasma
      efavirenz concentration of <1,000 ng/mL appear to have a high risk for the
      emergence of drug resistance. In the present study, we assessed the influence of
      the CYP2B6 polymorphism on the plasma efavirenz level. METHODS: CYP2B6 T18492C
      (rs2279345) in 149 HIV-infected Thai adults were genotyped. Plasma efavirenz
      concentrations 12 h after dosing were measured using a validated high-performance
      liquid chromatography. The relationship between the plasma efavirenz level and
      the CYP2B6 T18492C polymorphism were analysed. RESULTS: Among the 149 patients,
      the frequency of T18492C heterozygous (T/C) and homozygous mutant (C/C) was 38.26
      % (n = 57) and 6.04 % (n = 9), respectively. In the entire cohort, the median
      efavirenz plasma concentration was 2,410 ng/mL [interquartile range (IQR) 1,460
      4,120 ng/mL]. The plasma efavirenz concentration for patients with 18492CC (1,200
      ng/mL, IQR 1,050-1,990 ng/mL) or 18492TC (1,900 ng/mL, IQR 1,320-2,510 ng/mL)
      genotypes were significantly lower than those with homozygous wild type (3,380
      ng/mL, IQR 2,040-5,660 ng/mL), P-value < 0.001. CONCLUSIONS: The CYP2B6 T18492C
      polymorphism was significantly associated with lower efavirenz concentrations
      compared to those with homozygous wild type in HIV-1 infections. The genetic
      polymorphism CYP2B6 T18492C may be useful for the optimised efavirenz dose.
      Further studies in the clinical setting will need to be conducted before such an
      approach can be recommended for widespread use.

PMID- 24293078
TI  - Intertemporal analysis of organizational productivity in residential aged care
      networks: scenario analyses for setting policy targets.
AB  - With an increasing ageing population, there is a growing concern about how the
      elderly would be looked after. The primary purpose of this paper is to develop
      scenario analysis using simulated data where various criteria are incorporated
      into modeling policy targets, and apply an intertemporal productivity analysis to
      observe inefficiencies as reform unfolds. The study demonstrates how dynamic
      network data envelopment analysis (DN-DEA) can be used to evaluate the changing
      productivity of residential aged care (RAC) networks over time. Results indicate
      that it takes 9 years for 90 % of the RAC networks to have 85 % or more of the
      total beds in high-level care, and an optimal bed capacity is reached by the end
      of year 7. Number of beds and registered nurses employed are the main sources of
      inefficiency. The common core inefficient cohort identified with the paper's
      method represents a sub-group of RAC networks more deserving of closer managerial
      attention because of their constantly inefficient operations over time.

PMID- 24293079
TI  - Severe chest pain caused by Mycoplasma myocarditis in an adolescent patient.
AB  - Intermittent chest pain is a common symptom in adolescent patients, which can be
      attributed to musculoskeletal disorders in the majority of cases. While most
      patients have a benign course of their pain episodes, the differential diagnosis
      includes diseases which are associated with serious and even life-threatening
      complications. Therefore, careful examination and systematic diagnostic
      evaluation is important. We report on an adolescent, who presented with severe
      chest pain and distinct electrocardiographic findings caused by Mycoplasma
      pneumoniae myocarditis. 

PMID- 24293080
TI  - Meconium aspiration syndrome--a 21-years' experience from a tertiary care center
      and analysis of risk factors for predicting disease severity.
AB  - Aim of this study was to describe the course of perinatal factors in neonates
      with meconium aspiration syndrome (MAS) from 1990 to 2010 and to determine risk
      factors for a severe course of the disease.All neonates with MAS hospitalized in
      our level III neonatal intensive care unit from 1990 to 2010.Retrospective
      analysis of trends of perinatal factors in neonates with MAS over time and of the
      association of these factors with severe MAS (need for invasive mechanical
      ventilation for >=7 days, or need for high frequency oscillation or need for
      extracorporeal membrane oxygenation).We included 205 neonates with MAS, 55 had
      severe MAS (27%). MAS incidence and absolute number of MAS cases per year
      decreased during the observation period (p=0.003 and 0.005, respectively) as well
      as rates of outborn deliveries (p=0.004), duration of invasive mechanical
      ventilation (p=0.004), and hospital stay (p=0.036). Incidence and absolute number
      of severe MAS cases per year decreased (p=0.008 and 0.006, respectively), though
      the percentage of severe MAS among all neonates with MAS did not change. Risk
      factors for severe MAS were acute tocolysis (odds ratio 18.2 (95% confidence
      interval 2.1-155.3), p<0.001) fetal distress (3.4 (1.8-6.4), p<0.001), and severe
      and moderate birth asphyxia (4.4 (2.0-9.7), p=0.001 and 2.9 (1.5-5.6),
      p=0.009).The incidence and absolute numbers of MAS and severe MAS cases changed
      during the study period as well as neonatal management. Acute tocolysis, fetal
      distress, and asphyxia were associated with severe MAS.

PMID- 24293081
TI  - Fear of recurrence in long-term breast cancer survivors-still an issue. Results
      on prevalence, determinants, and the association with quality of life and
      depression from the cancer survivorship--a multi-regional population-based study.
AB  - BACKGROUND: Fear of recurrence (FoR) is a widespread problem among breast cancer
      survivors. So far, little is known about prevalence, determinants, and
      consequences of FoR specifically in long-term breast cancer survivors, even
      though it was found to be one of the most important concerns in this group.
      METHODS: Analyses are based on data of several population-based cohorts of long
      term breast cancer survivors, recruited by six German cancer registries. Overall,
      2671 women were included in the analyses. FoR was assessed using the short form
      of the Fear of Progression Questionnaire. Potential determinants of moderate/high
      FoR and the association with depression and quality of life (QoL) were explored
      via multiple logistic and linear regression. RESULTS: Even though the majority of
      women reported low levels of FoR (82%), a substantial percentage experienced
      moderate (11%) and high (6%) FoR. Younger age (odds ratio = 3.00, confidence
      intervals = 1.91-4.73 for women below age 55 years) and considering oneself as a
      tumor patient (odds ratio = 3.36, confidence intervals = 2.66-4.25) were found to
      exhibit the strongest associations with moderate/high FoR. Overall, psychosocial
      and sociodemographic factors played a far bigger role in FoR than clinical
      factors. Higher FoR was associated with higher depression and lower QoL.
      CONCLUSION: Fear of recurrence (mostly low levels) is highly prevalent among long
      term breast cancer survivors and can negatively affect QoL and well-being.
      Therefore, it should be given appropriate consideration in research and clinical
      practice. As specifically younger women tended to be impacted by FoR, it is
      crucial to be particularly attentive to specific needs of younger survivors.

PMID- 24293082
TI  - Application of synchrotron X-ray microtomography for visualizing bacterial
      biofilms 3D microstructure in porous media.
AB  - The development of reliable models to accurately predict biofilm growth in porous
      media relies on a good knowledge of the temporal evolution of biofilms structure
      within the porous network. Since little is known on the true 3D structure of
      biofilms developed in porous media, this work aimed at developing a new
      experimental protocol to visualize the 3D microstructure of bacterial biofilms in
      porous media. The main originality of the proposed procedure lies on the
      combination of the more recent advances in synchrotron microtomography (Paganin
      mode) and of a new contrast agent (1-chloronaphtalene) that has never been
      applied to biofilm visualization. It is shown that the proposed methodology takes
      advantage of the contrasting properties of 1-chloronaphtalene to prevent some
      limitations observed with more classical contrast agents. A quantitative analysis
      of the microstructural properties (volume fractions and specific surface area) of
      bacterial biofilms developed in columns of clay beads is also proposed on the
      basis of the obtained 3D images.

PMID- 24293084
TI  - Ulnar neuropathy at the elbow.

PMID- 24293083
TI  - Sex differences in social perception in children with ASD.
AB  - Autism spectrum disorder (ASD) is more common in males than females. An
      underrepresentation of females in the ASD literature has led to limited knowledge
      of differences in social function across the sexes. Investigations of face
      perception represent a promising target for understanding variability in social
      functioning between males and females. The current study analyzed
      electrophysiological brain recordings during face perception to investigate sex
      differences in the neural correlates of face perception and their relationship to
      social function. Event related potentials (ERP) were recorded from children with
      ASD while viewing faces, inverted faces, and houses. Relative to males, females
      showed attenuated response at an ERP marker of face perception, the N170. Among
      females, but not males, atypical face response was associated with symptom
      severity. Observed sex differences reflect influential differences in social
      information processing, and impairment in these features correlates with deficits
      in social information processing in females, but not males, with ASD. These
      findings hold significance for future treatment protocols, which should account
      for differences in males and females with ASD in clinical presentation and neural
      phenotypes. 

PMID- 24293085
TI  - Saving a life but losing the patient.
AB  - Gregor Samsa awakes to find himself transformed into a gigantic bug. The
      creature's inchoate flailing leads Gregor's sister to conclude that Gregor is no
      more, having been replaced by a brute beast lacking any vestige of human
      understanding. Sadly, real cases of brain injury and disease can lead to
      psychological metamorphoses so profound that we cannot easily think that the
      survivor is the person we knew. I argue that there can be cases in which
      statements like, "It's just not Gregor anymore," are not merely figures of
      speech. With this in mind, I consider three possible results of saving a
      biological life: (1) ordinary cases where saving the life will save the person,
      with strong duties to save the life; (2) cases where the intervention needed to
      save the life will replace the person, with strong duties not to save the life;
      (3) cases in which it is indeterminate whether the person will be saved or
      replaced. How should we think about indeterminate cases? Impersonal ethical
      considerations miss the point, while standard person-affecting considerations are
      inapplicable. I suggest turning attention away from survival towards a richer
      focus on what I call "personal concern." I show how considerations of personal
      concern, unlike those of self-interest, need not be tied to survival and how this
      allows personal concern to provide a basis for ethically substantive discussion
      of cases where saving a life might result in losing the patient. 

PMID- 24293087
TI  - Dermatitis herpetiformis: clinical presentations are independent of
      manifestations of celiac disease.
AB  - BACKGROUND: Dermatitis herpetiformis (DH) is a skin manifestation of celiac
      disease (CD), and is often the presenting and only complaint. There are few data
      comparing those with DH who present only with DH and those with DH who present
      mainly due to CD. OBJECTIVE: We compared the prevalence of features usually
      associated with CD in those who presented with DH with patients in whom DH was
      part of a typical CD presentation. METHODS: A cross-sectional study of a
      prospectively maintained database of 1,050 patients with CD was analyzed. Only
      biopsy-diagnosed patients were analyzed for small bowel findings. All patients
      were included in the analysis of autoimmune diseases and lymphoma incidence.
      Small bowel biopsies were classified into mild and severe. RESULTS: The
      prevalence of villous atrophy was significantly higher in the patients who
      presented with CD than in those who presented with DH alone (61.8 vs. 12.5%; p =
      0.005). However, the prevalence of nutritional deficiencies, autoimmune diseases,
      and lymphoma occurred at a similar rate in patients with DH and patients with CD
      without DH. CONCLUSIONS: Patients who present with CD and concurrent DH are more
      likely to have more severe pathology than those with predominantly DH, although
      nutritional deficiencies are similar between the two groups. It is important to
      screen for nutritional deficiencies in patients with DH, irrespective of the
      presence of typical CD manifestations.

PMID- 24293086
TI  - Meta-analysis shows clinically relevant and long-lasting deterioration in health
      related quality of life after esophageal cancer surgery.
AB  - PURPOSE: The purpose of the study is to (1) estimate the direction, clinical
      relevance, and duration of health-related quality-of-life (HRQL) change in the
      first year following esophageal cancer surgery and (2) to assess the robustness
      of the estimates by subgroup and sensitivity analyses, and an exploration of
      publication bias. METHODS: A systematic literature search in MEDLINE, EMBASE,
      CINAHL, PsychINFO, and CENTRAL to identify randomized and non-randomized studies
      was performed. We compared the baseline HRQL data with 3-, 6-, 9-, or 12-month
      follow-ups to estimate the magnitude and duration of HRQL change. These estimates
      were then classified as trivial, small, medium, or large. Primary outcomes were
      role functioning, eating, and fatigue. Secondary outcomes were physical and
      social functioning, dysphagia, pain, and coughing problems. We conducted subgroup
      analysis for open surgery, open surgery preceded by neoadjuvant therapy, and
      minimally invasive surgery. Sensitivity analyses assessed the influence of study
      design, transformation/imputation of the data, and HRQL questionnaire used.
      RESULTS: We included the data from 15 studies to estimate the change in 28 HRQL
      outcomes after esophageal cancer surgery. The main analysis showed that patients'
      social functioning deteriorated. Symptoms of fatigue, pain, and coughing problems
      increased. These changes lasted for 9-12 months, although some symptoms persisted
      beyond the first year after surgery. For many other HRQL outcomes, estimates were
      only robust after subgroup or sensitivity analyses (e.g., role and physical
      functioning), or remained too heterogeneous to interpret (e.g., eating and
      dysphagia). CONCLUSIONS: Patients will experience a clinically relevant and long
      lasting deterioration in HRQL after esophageal cancer surgery. However, for many
      HRQL outcomes, more and better quality evidence is needed.

PMID- 24293088
TI  - Sphenopalatine ganglion neuromodulation in migraine: what is the rationale?
AB  - OBJECTIVE: The objective of this article is to review the prospect of treating
      migraine with sphenopalatine ganglion (SPG) neurostimulation. BACKGROUND: Fuelled
      by preliminary studies showing a beneficial effect in cluster headache patients,
      the potential of treating migraine with neurostimulation has gained increasing
      interest within recent years, as current treatment strategies often fail to
      provide adequate relief from this debilitating headache. Common migraine symptoms
      include lacrimation, nasal congestion, and conjunctival injection, all
      parasympathetic manifestations. In addition, studies have suggested that
      parasympathetic activity may also contribute to the pain of migraineurs. The SPG
      is the largest extracranial parasympathetic ganglion of the head, innervating the
      meninges, lacrimal gland, nasal mucosa, and conjunctiva, all structures involved
      in migraine with cephalic autonomic symptoms. CONCLUSION: We propose two possible
      mechanisms of action: 1) interrupting the post-ganglionic parasympathetic outflow
      to inhibit the pain and cephalic autonomic symptoms, and 2) modulating the
      sensory processing in the trigeminal nucleus caudalis. To further explore SPG
      stimulation in migraineurs as regards therapeutic potential and mode of action,
      randomized clinical trials are warranted.

PMID- 24293089
TI  - Definitions of medication-overuse headache in population-based studies and their
      implications on prevalence estimates: a systematic review.
AB  - BACKGROUND: Case definitions of medication-overuse headache (MOH) in population
      based research have changed over time. This study aims to review MOH prevalence
      reports with respect to these changes, and to propose a practical case definition
      for future studies based on the ICHD-3 beta. METHODS: A systematic literature
      search was conducted to identify MOH prevalence studies. Findings were summarized
      according to diagnostic criteria. RESULTS: Twenty-seven studies were included.
      The commonly used case definition for MOH was headache >=15 days/month with
      concurrent medication overuse >=3 months. There were varying definitions for what
      was considered as overuse. Studies that all used ICHD-2 criteria showed a wide
      range of prevalence among adults: 0.5%-7.2%. CONCLUSIONS: There are limits to
      comparing prevalence of MOH across studies and over time. The wide range of
      reported prevalence might not only be due to changing criteria, but also the
      diversity of countries now publishing data. The criterion "headache occurring on
      >=15 days per month" with concurrent medication overuse can be applied in
      population-based studies. However, the new requirement that a respondent must
      have "a preexisting headache disorder" has not been previously validated.
      Exclusion of other headache diagnoses by expert evaluation and ancillary
      examinations is not feasible in large population-based studies.

PMID- 24293090
TI  - Integrated primary care improves access to healthcare for newly arrived refugees
      in Canada.
AB  - In this study we quantify the impact of a partnership between a dedicated health
      clinic for government assisted refugees (GARs), a local reception centre and
      community providers, on wait times and referrals. This study used a before and
      after, repeated survey study design to analyze archived administrative data.
      Using various statistical techniques, outcomes for refugees arriving 18 months
      prior to the introduction of the clinic were compared with those of refugees
      arriving in the 18 months after the clinic was established. Our investigation
      revealed wait times to see a health care provider decreased by 30 % with the
      introduction of a dedicated refugee health clinic. The likelihood of GARs being
      referred to physician specialists decreased by 45 %, but those referred were more
      likely to require multiple referrals due to increasingly complex medical needs.
      Referrals to non-physician specialist health care providers nearly doubled
      following the availability of the clinic. The time-limited, but intense health
      needs of GARs, require an integrated community-based primary healthcare
      intervention that includes dedicated health system navigators to support timely,
      more culturally appropriate care and successful integration.

PMID- 24293091
TI  - Incidence and risk factors for central venous catheter-related thrombosis in
      hematological patients.
AB  - Catheter-related thrombosis (CRT) is a serious complication in hematological
      patients, but the risk factors for its occurrence are not well established. The
      study objectives were to estimate the incidence of CRT and to identify the risk
      factors for developing CRT in hematological patients. In a prospective setting,
      104 consecutive patients with 200 insertions of central venous catheters were
      enrolled into the study. The patients were screened for CRT by compression
      Doppler ultrasound every 10-14 days. Additionally, ultrasonography was performed
      in the case of clinical symptoms suggesting CRT. Over the course of 6,098
      catheter days of follow-up, the incidence of CRT was 13.5 %. In 18/27 cases (66.6
      %), radiological evidence of CRT was preceded by clinical symptoms. However, in
      9/27 (33.3 %), CRT was clinically asymptomatic. The median times to symptomatic
      and asymptomatic CRT were 17 (range 1-49) and 8 (range 1-16) catheter days,
      respectively. In univariate analysis, the risk factors for CRT were exit-site
      infection (ESI) (P < 0.001), two or more prior chemotherapy lines (P = 0.015),
      catheter-related blood stream infection (P < 0.001), and Coagulase-negative
      staphylococci infection (P = 0.002). In multivariate analysis, ESI (OR 5.0; 95 %
      CI 1.6-6.3; P = 0.006) and two or more prior chemotherapy lines (OR 3.57; 95 % CI
      1.27-10.11; P = 0.015) remained significantly associated with the risk of CRT.
      The results of our study provide information regarding the characteristic
      features of the patients who are at high risk of thrombosis, for whom Doppler
      ultrasound screening should be considered.

PMID- 24293092
TI  - The expression of miR-25 is increased in colorectal cancer and is associated with
      patient prognosis.
AB  - MicroRNA-25 (miR-25) has recently been found to be involved in many critical
      processes in human malignancies. We aimed to investigate the expression pattern
      and prognostic role of miR-25 in colorectal cancer. Colorectal cancer and
      adjacent normal specimens from 186 patients who had not received neoadjuvant
      chemotherapy were collected. The expression of miR-25 was detected with a
      quantitative real-time PCR assay, and the association of miR-25 with overall
      patient survival was analyzed via statistical analysis. The results indicated
      that the level of miR-25 expression was significantly elevated in colorectal
      cancer compared with the level observed in the adjacent normal tissue. It was
      also demonstrated that miR-25 expression is associated with tumor invasion, lymph
      node metastasis, distant metastasis and the TNM stage of colorectal cancer. In
      addition, a Kaplan-Meier analysis revealed that an increased level of miR-25
      expression is associated with a poor overall survival of patients. A multivariate
      survival analysis also indicated that miR-25 is an independent prognostic marker
      after adjusting for known prognostic factors. These results prove that miR-25
      expression is increased in colorectal cancer and is associated with tumor
      progression. This study also provides the first evidence that miR-25 is an
      independent prognostic factor for patients with colorectal cancer, indicating the
      potential role of miR-25 as a highly specific and sensitive biomarker. 

PMID- 24293093
TI  - Functional polymorphism of CYP2B6 G15631T is associated with hematologic and
      cytogenetic response in chronic myeloid leukemia patients treated with imatinib.
AB  - In the spite of the impressive results achieved with imatinib in chronic myeloid
      leukemia (CML) patients, differences in patient's response are observed, which
      may be explained by interindividual genetic variability. It is known that
      cytochrome P450 enzymes play a major role in the metabolism of imatinib. The
      present study aimed to understand the functional impact of CYP2B6 15631G>T
      polymorphism on the response of imatinib in CML patients and its relation to CML
      susceptibility. We have genotyped CYP2B6 G15631T in 48 CML patients and 64
      controls by PCR-RFLP. CYP2B6 15631G>T was not found to be a risk factor for CML
      (OR 95 % CI, 1.12, 0.6-2, p > 0.05). Hematologic response loss was higher in
      patients with 15631GG/TT genotype when compared with 15631GT (36.8 vs. 13.8 %; X
      (2) = 3.542, p = 0.063). Complete cytogenetic response was higher in 15631GG/GT
      genotype groups when compared with 15631TT (X (2) = 3.298, p = 0.024). Primary
      cytogenetic resistance was higher in patients carrying 15631GG/TT genotype when
      compared with 15631GT carriers (52.6 vs. 17.2 %; X (2) = 6.692, p = 0.010).
      Furthermore, side effects were more common for patients carrying 15631GG
      genotypes when compared with GT/TT carriers (36 vs. 13.8 %; X (2) = 8.3, p =
      0.004). In light of our results, identification of 15631G>T polymorphism in CML
      patients might be helpful to predict therapeutic response to imatinib.

PMID- 24293094
TI  - Spatial heterogeneity in the response of the proximal femur to two lower-body
      resistance exercise regimens.
AB  - Understanding the skeletal effects of resistance exercise involves delineating
      the spatially heterogeneous response of bone to load distributions from different
      muscle contractions. Bone mineral density (BMD) analyses may obscure these
      patterns by averaging data from tissues with variable mechanoresponse. To assess
      the proximal femoral response to resistance exercise, we acquired pretraining and
      posttraining quantitative computed tomography (QCT) images in 22 subjects (25-55
      years, 9 males, 13 females) performing two resistance exercises for 16 weeks. One
      group (SQDL, n = 7) performed 4 sets each of squats and deadlifts, a second group
      (ABADD, n = 8) performed 4 sets each of standing hip abductions and adductions,
      and a third group (COMBO, n = 7) performed two sets each of squat/deadlift and
      abduction/adduction exercise. Subjects exercised three times weekly, and the load
      was adjusted each session to maximum effort. We used voxel-based morphometry
      (VBM) to visualize BMD distributions. Hip strength computations used finite
      element modeling (FEM) with stance and fall loading conditions. We used QCT
      analysis for cortical and trabecular BMD, and cortical tissue volume. For muscle
      size and density, we analyzed the cross-sectional area (CSA) and mean Hounsfield
      unit (HU) in the hip extensor, flexor, abductor, and adductor muscle groups.
      Whereas SQDL increased vertebral BMD, femoral neck cortical BMD and volume, and
      stance hip strength, ABADD increased trochanteric cortical volume. The COMBO
      group showed no changes in any parameter. VBM showed different effects of ABADD
      and SQDL exercise, with the former causing focal changes of trochanteric cortical
      bone, and the latter showing diffuse changes in the femoral neck and head. ABADD
      exercise increased adductor CSA and HU, whereas SQDL exercise increased the hip
      extensor CSA and HU. In conclusion, we observed different proximal femoral bone
      and muscle tissue responses to SQDL and ABADD exercise. This study supports VBM
      and volumetric QCT (vQCT) to quantify the spatially heterogeneous effects of
      types of muscle contractions on bone.

PMID- 24293095
TI  - A coronary "tunnel": optical coherence tomography assessment after rotational
      atherectomy.
AB  - A 81-year-old woman was admitted for exertional angina. Coronary angiogram
      revealed a severely calcific proximal circumflex lesion. Rotational atherectomy
      was performed with 1.5 and 1.75 burrs, obtaining a good angiographic result.
      Optical coherence tomography (OCT) assessment revealed a large dissection
      parallel to the true lumen. We implanted a 3.0 mm * 38 mm Xience Prime((r)) stent
      and postdilated it with a 3.0-mm non-compliant balloon. Final OCT pullback showed
      mild malapposed struts with large lumen area. 3D-OCT reconstruction confirmed a
      large lumen after stent implantation.

PMID- 24293096
TI  - Articular cartilage regeneration using cell sheet technology.
AB  - Cartilage damage is typically treated by chondrocyte transplantation,
      mosaicplasty, or microfracture. Recent advances in tissue engineering have
      prompted research on techniques to repair articular cartilage damage using a
      variety of transplanted cells. We studied the repair and regeneration of
      cartilage damage using layered chondrocyte sheets prepared in a temperature
      responsive culture dish. We previously reported achieving robust tissue repair
      when covering only the surface layer of partial-thickness defects with layered
      chondrocyte sheets in domestic rabbits. We also reported good Safranin O staining
      and integration with surrounding tissue in a minipig model of full-thickness
      cartilaginous defects in the knee joint. We have continued our studies using
      human chondrocytes obtained from patients under IRB approval, and have confirmed
      the safety and efficacy of chondrocyte sheets, and have submitted a report to the
      Ministry of Health, Labour, and Welfare in Japan. In 2011, the Ministry gave us
      approval to perform a clinical study of joint repair using cell sheets. We have
      just started implanting cell sheets in patients at Tokai University Hospital.

PMID- 24293097
TI  - Patients will be involved in assessing CCGs, NHS England decides.

PMID- 24293099
TI  - Everolimus for the treatment of subependymal giant cell astrocytoma probably
      causing seizure aggravation in a child with tuberous sclerosis complex: a case
      report.
AB  - We are reporting on a 13.5-year-old girl with tuberous sclerosis complex (TSC)
      who was treated with everolimus because of giant cell astrocytoma and bilateral
      angiomyolipoma. She suffered from pharmacoresistant partial epilepsy with
      clusters of tonic and tonic-clonic seizures. Treatment with carbamazepine and
      sulthiame had led to a stable situation for more than 2.5 years. The dosage of
      everolimus had to be increased and refractory status epilepticus followed after
      12 days. In the absence of any other possible cause, we believe that the status
      epilepticus was provoked by everolimus. So far, only a few cases of possible
      seizure aggravation by everolimus have been reported. The clinical relevance of
      possible negative effects in epileptic patients remains unclear. Similar
      observations should be documented and reported. 

PMID- 24293100
TI  - Robotic-assisted rehabilitation for Parsonage-Turner syndrome.

PMID- 24293098
TI  - Pharmacologic augmentation of implant fixation in osteopenic bone.
AB  - Osteoporosis presents a challenge for successful implant fixation due to an
      impaired healing response. Preclinical studies have consistently reported reduced
      osseointegration capability in trabecular bone. Although clinical studies of
      implant success in dentistry have not found a negative effect due to
      osteoporosis, low bone mass is a significant risk factor for implant migration in
      orthopedics. Pharmacologic treatment options that limit bone resorption or
      upregulate formation have been studied preclinically. While, both treatment
      options improve implant fixation, direct comparisons to-date have found anti
      catabolic more effective than anabolic treatments for establishing implant
      fixation, but combination approaches are better than either treatment alone.
      Clinically, anti-catabolic treatments, particularly bisphosphonates have been
      shown to increase the longevity of implants, while limited clinical evidence on
      the effects of anabolic treatment exists. Preclinical experiments are needed to
      determine the effects of osteoporosis and subsequent treatment on the long-term
      maintenance of fixation and recovery after bone loss. 

PMID- 24293101
TI  - A nonclassical IFITM5 mutation located in the coding region causes severe
      osteogenesis imperfecta with prenatal onset.
AB  - Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder
      characterized by a wide range of skeletal symptoms. Most patients have dominantly
      inherited or de novo mutations in COL1A1 or COL1A2. Up to 5% of patients have OI
      type V, characterized by hyperplastic callus formation after fractures,
      calcification of the interosseous membrane of the forearm, and a mesh-like
      lamellation pattern observed in bone histology. Recently, a heterozygous mutation
      in the 5'-untranslated region (UTR) of IFITM5 (c.-14C > T) was identified as the
      underlying cause of OI type V, and only this specific mutation was subsequently
      identified in all patient cohorts with this OI subtype. We now present a case of
      a heterozygous mutation within the coding region of IFITM5 (c.119C > T; p.S40L).
      The mutation occurred de novo in the patient and resulted in severe OI with
      prenatal onset and extreme short stature. At the age of 19 months, the typical
      clinical hallmarks of OI type V were not present. Our finding has important
      consequences for the genetic "work-up" of patients suspected to have OI, both in
      prenatal and in postnatal settings: The entire gene-not only the 5'-UTR harboring
      the "classical" OI type V mutation-has to be analyzed to exclude a causal role of
      IFITM5. We propose that this should be part of the initial diagnostic steps for
      genetic laboratories performing SANGER sequencing in OI patients.

PMID- 24293102
TI  - Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b
      in Alzheimer's disease (AD) and in primary human neuronal-glial (HNG) cells.
AB  - Inducible microRNAs (miRNAs) perform critical regulatory roles in central nervous
      system (CNS) development, aging, health, and disease. Using miRNA arrays, RNA
      sequencing, enhanced Northern dot blot hybridization technologies, Western
      immunoblot, and bioinformatics analysis, we have studied miRNA abundance and
      complexity in Alzheimer's disease (AD) brain tissues compared to age-matched
      controls. In both short post-mortem AD and in stressed primary human neuronal
      glial (HNG) cells, we observe a consistent up-regulation of several brain
      enriched miRNAs that are under transcriptional control by the pro-inflammatory
      transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA
      146a, and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is
      among the most abundant and significantly induced miRNA species in human brain
      cells and tissues. Bioinformatics analysis indicated that an up-regulated miRNA
      125b could potentially target the 3'untranslated region (3'-UTR) of the messenger
      RNA (mRNA) encoding (a) a 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized
      in the conversion of docosahexaneoic acid into neuroprotectin D1 (NPD1), and (b)
      the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor
      superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid
      mediated signaling, neurotrophic support, defense against reactive oxygen and
      nitrogen species (reactive oxygen and nitrogen species), and neuroprotection in
      the CNS. Pathogenic effects appear to be mediated via specific interaction of
      miRNA-125b with the 3'-UTR region of the 15-LOX and VDR messenger RNAs (mRNAs).
      In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation
      and a deficiency in neurotrophic support may therefore be explained by the
      actions of a single inducible, pro-inflammatory miRNA-125b. We will review the
      recent data on the pathogenic actions of this up-regulated miRNA-125b in AD and
      discuss potential therapeutic approaches using either anti-NF-kB or anti-miRNA
      125b strategies. These may be of clinical relevance in the restoration of 15-LOX
      and VDR expression back to control levels and the re-establishment of homeostatic
      neurotrophic signaling in the CNS. 

PMID- 24293104
TI  - Molecular phylogeny of elasmobranchs inferred from mitochondrial and nuclear
      markers.
AB  - The elasmobranchs (sharks, rays and skates) being the extant survivors of one of
      the earliest offshoots of the vertebrate evolutionary tree are good model
      organisms to study the primitive vertebrate conditions. They play a significant
      role in maintaining the ecological balance and have high economic value. Due to
      over-exploitation and illegal fishing worldwide, the elasmobranch stocks are
      being decimated at an alarming rate. Appropriate management measures are
      necessary for restoring depleted elasmobranch stocks. One approach for restoring
      stocks is implementation of conservation measures and these measures can be
      formulated effectively by knowing the evolutionary relationship among the
      elasmobranchs. In this study, a total of 30 species were chosen for molecular
      phylogeny studies using mitochondrial cytochrome c oxidase subunit I, 12S
      ribosomal RNA gene and nuclear Internal Transcribed Spacer 2. Among different
      genes, the combined dataset of COI and 12S rRNA resulted in a well resolved tree
      topology with significant bootstrap/posterior probabilities values. The results
      supported the reciprocal monophyly of sharks and batoids. Within Galeomorphii,
      Heterodontiformes (bullhead sharks) formed as a sister group to Lamniformes
      (mackerel sharks): Orectolobiformes (carpet sharks) and to Carcharhiniformes
      (ground sharks). Within batoids, the Myliobatiformes formed a monophyly group
      while Pristiformes (sawfishes) and Rhinobatiformes (guitar fishes) formed a
      sister group to all other batoids.

PMID- 24293105
TI  - Carcinoembryonic antigen expression level as a predictive factor for response to
      5-fluorouracil in colorectal cancer.
AB  - Carcinoembryonic antigen (CEA) expression has been shown to protect cancer cell
      lines from apoptosis and anoikis. The aim of this study was to further elucidate
      the role of CEA expression on resistance to anticancer drugs in human colorectal
      cancer (CRC). We transfected CEA negative CRC cell line SW742 as well as CHO
      cells to overexpress CEA and their chemoresistance were assessed by MTT assay. In
      comparison to the parental cell lines, transfected cells had significantly
      increased resistance to 5-fluorouracil (5-FU). The results also showed a direct
      correlation between the amount of cellular CEA protein and 5-FU resistance in CEA
      expressing cells. We found no significant difference in sensitivity to cisplatin
      and methotrexate between CEA-transfected cells and their counter parental cells.
      We also compared the association between CEA expression and chemoresistance of 4
      CRC cell lines which differed in the levels of CEA production. The CEA expression
      levels in monolayer cultures of these cell lines did not correlate with the 5-FU
      resistance. However, 5-FU treatment resulted in the selection of sub-populations
      of resistant cells that displayed increased CEA expression levels by increasing
      drug concentration. We analyzed the effect of 5-FU in a 3D multicellular culture
      generated from the two CRC cell lines, LS180 and HT29/219. Compared with
      monolayer culture, CEA production and 5-FU resistance in both cell lines were
      stimulated by 3D growth. In comparison to the 3D spheroids of parental CHO, we
      observed a significantly elevated 5-FU resistance in 3D culture of the CEA
      expressing CHO transfectants. Our findings suggest that the CEA level may be a
      suitable biomarker for predicting tumor response to 5-FU-based chemotherapy in
      CRC.

PMID- 24293103
TI  - Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current
      insights and emerging therapeutic strategies.
AB  - Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important
      functions in the proteasomal protein degradation pathway and regulation of
      transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine
      (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the
      neurodegenerative disease spinocerebellar ataxia 3 (SCA3). In spite of extensive
      research, the molecular mechanisms underlying the cellular toxicity resulting
      from mutant ataxin-3 remain elusive and no preventive treatment is currently
      available. It has become clear over the last decade that the hallmark
      intracellular ataxin-3 aggregates are likely not the main toxic entity in SCA3.
      Instead, the soluble PolyQ containing fragments arising from proteolytic cleavage
      of ataxin-3 by caspases and calpains are now regarded to be of greater influence
      in pathogenesis. In addition, recent evidence suggests potential involvement of a
      RNA toxicity component in SCA3 and other PolyQ expansion disorders, increasing
      the pathogenic complexity. Herein, we review the functioning of ataxin-3 and the
      involvement of known protein and RNA toxicity mechanisms of mutant ataxin-3 that
      have been discovered, as well as future opportunities for therapeutic
      intervention. 

PMID- 24293107
TI  - Membrane potential-dependent binding of polysialic acid to lipid monolayers and
      bilayers.
AB  - Polysialic acids are linear polysaccharides composed of sialic acid monomers.
      These polyanionic chains are usually membrane-bound, and are expressed on the
      surfaces of neural, tumor and neuroinvasive bacterial cells. We used toluidine
      blue spectroscopy, the Langmuir monolayer technique and fluorescence spectroscopy
      to study the effects of membrane surface potential and transmembrane potential on
      the binding of polysialic acids to lipid bilayers and monolayers. Polysialic acid
      free in solution was added to the bathing solution to assess the metachromatic
      shift in the absorption spectra of toluidine blue, the temperature dependence of
      the fluorescence anisotropy of DPH in liposomes, the limiting molecular area in
      lipid monolayers, and the fluorescence spectroscopy of oxonol V in liposomes. Our
      results show that both a positive surface potential and a positive transmembrane
      potential inside the vesicles can facilitate the binding of polysialic acid
      chains to model lipid membranes. These observations suggest that these membrane
      potentials can also affect the polysialic acid-mediated interaction between
      cells. 

PMID- 24293106
TI  - A clinical and pharmacologic assessment of once-daily versus twice-daily dosing
      for rivaroxaban.
AB  - Altering doses and regimens of a drug has consequences for the drug's
      pharmacokinetic and pharmacodynamic profile. Based on a half-life of 5-13 h, it
      is expected that the Factor Xa inhibitor rivaroxaban would be best suited to a
      twice-daily rather than a once-daily dose regimen. However, although rivaroxaban
      is used as a twice-daily regimen for the initial treatment of venous
      thromboembolism (VTE) and secondary prevention after acute coronary syndromes,
      the approved dosing is once-daily for prevention of VTE after orthopaedic
      surgery, long-term secondary prevention of VTE and stroke prevention in patients
      with non-valvular atrial fibrillation. Rivaroxaban dosing was based on the
      evaluation of the efficacy and safety of several rivaroxaban doses and regimens
      in phase II trials. A clear overall advantage of twice-daily dosing compared with
      once-daily dosing was not documented for indications for which once-daily dosing
      was subsequently selected. Once-daily dosing was therefore selected for these
      indications because it is expected to be associated with better compliance than
      twice-daily dosing, and potentially, with improved outcomes. These studies and
      data obtained with another Factor Xa inhibitor, edoxaban, in addition to previous
      experience with low molecular weight heparins, indicate that the clinical impact
      of once-daily versus twice-daily doses on outcome in terms of efficacy and safety
      cannot be reliably predicted from pharmacology data, e.g. elimination half-life,
      obtained during pre-clinical and early phase I clinical studies but rather should
      be ascertained empirically in phase II and III clinical trials. 

PMID- 24293108
TI  - The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor
      mRNA expression in human breast cancer.
AB  - Lamin A/C (LMNA), lamin B1 (LMNB1) and lamin B receptor (LBR) have key roles in
      nuclear structural integrity and chromosomal stability. In this study, we have
      studied the relationships between the mRNA expressions of A-type lamins, LMNB1
      and LBR and the clinicopathological parameters in human breast cancer. Samples of
      breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT; n =
      30) were assessed using reverse transcription and quantitative PCR. Transcript
      levels were correlated with clinicopathological data. Higher levels of A-type
      lamins and LMNB1 mRNA expression were seen in ANCT. Higher lamin A/C expression
      was associated with the early clinical stage (TNM1 vs. TNM3 - 13 vs. 0.21; p =
      0.0515), with better clinical outcomes (disease-free survival vs. mortality - 11
      vs. 1; p = 0.0326), and with better overall (p = 0.004) and disease-free survival
      (p = 0.062). The expression of LMNB1 declined with worsening clinical outcome
      (disease-free vs. mortalities - 0.0011 vs. 0.000; p = 0.0177). LBR mRNA
      expression was directly associated with tumor grade (grade 1 vs. grade 3 - 0.00
      vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 - 0.00 vs.
      0.00; p = 0.0551). To the best of our knowledge, this is the first study to
      suggest such a role for A-type lamins, lamin B1 and LBR in human breast cancer,
      identifying an important area for further research. 

PMID- 24293111
TI  - Tissue engineering in the vasculature.
AB  - Tissue engineering holds great promise to address complications and limitations
      encountered with the use of traditional prosthetic materials, such as
      thrombogenicity, infection, and future degeneration which represent the major
      morbidity and mortality after device implant surgery. The general concept of
      tissue engineering consists of three main components: a scaffold material, a cell
      type for seeding the scaffold, and biochemical, physio-chemical signaling and
      remodeling process. This remodeling process is guided by cell signals derived
      from both seeded cells and host inflammatory cells that infiltrate the scaffold
      and deposit extracellular matrix, forming the neotissue. Vascular tissue
      engineering is at the forefront in the translation of this technology to clinical
      practice, as tissue engineered vascular grafts (TEVGs) have now been successfully
      implanted in children with congenital heart disease. In this report, we review
      the history, advances, and state of the art in TEVGs.

PMID- 24293110
TI  - Cancer-induced oxidative stress and pain.
AB  - Cancer pain is a well-documented and prevalent healthcare problem, with current
      treatment strategies often failing to achieve acceptable efficacy. One of the
      major difficulties in treating cancer pain owes to the complex interplay between
      the cancer microenvironment, cancer therapy, and the body's own responses to
      these biochemical changes. A better understanding of the molecular pathways of
      nociception that are activated during cancer progression and treatment is
      necessary for better pain management and increased quality of life. This article
      reviews the current research that implicates oxidative stress as an important
      target for attenuating cancer pain. Sources of oxidative stress are first
      established, followed by a discussion of the various pathways that are affected
      by oxidative stress and that ultimately cause cancer pain. 

PMID- 24293113
TI  - Aging as a social form: the phenomenology of the passage.
AB  - If philosophers have discussed life as preparation for death, this seems to make
      aging coterminous with dying and a melancholy passage that we are condemned to
      survive. It is important to examine the discourse on aging and end of life and
      the ways various models either limit possibilities for human agency or suggest
      means of being innovative in relation to such parameters. I challenge
      developmental views of aging not by arguing for eternal life, but by using
      Plato's conception of form in conjunction with Simmel's work and Arendt's
      meditation on intergenerational solidarity, to evoke a picture of the subject as
      having capacities that offer avenues for improvisational action. This paper
      proposes a method for analyzing any social form as a problem-solving situation
      where the real "problem" is the fundamental ambiguity that inheres in the mix
      between the finite characteristics of the action and its infinite perplexity. I
      work through the most conventional chronological view of aging to show how it
      dramatizes a fundamental ethical collision in life that intensifies anxiety under
      many conditions, always raising the question of what is to be done with respect
      to contingency, revealing such "work" as a paradigm of the human condition. 

PMID- 24293112
TI  - DMPPQA, a novel angiogenesis inhibitor, induces apoptosis in human colon cancer
      HCT-116 cells and HUVECs.
AB  - Cytotoxic activity of 5,7-dimethoxy-2-phenyl-N-propylquinolin-4-amine (DMPPQA)
      was investigated in human colon cancer cells HCT-116 and umbilical vein
      endothelial cell line HUVEC. The IC(50) of DMPPQA on HCT-116 and HUVEC cells were
      respectively 1.26 and 7.43 uM after 72 h treatment. DMPPQA inhibited the growth
      of HCT-116 and HUVEC cells in concentration- and time-dependent manners. Typical
      morphological changes of apoptotic body formation were seen after DMPPQA with
      Hoechst 33258 staining. FCM analysis showed that DMPPQA induced apoptosis,
      mitochondrial membrane potential loss (DeltaPsim) and increase in the production
      of intracellular reactive oxygen species (ROS) of HCT-116 cells. After treating
      with DMPPQA, apoptosis-related protein expression of Bax, cytochrome c, caspase
      9, caspase-3, PARP-1 and P53 increased and Bcl-2 protein expression decreased.
      DMPPQA treatment of HUVECs reduced cell migration and microcapillary tube
      formation in a Matrigel matrix. It also decreased VEGF protein expression. Thus
      DMPPQA acts as an angiogenesis inhibitor and induces cell apoptosis by a caspase
      dependent mitochondrial pathway.

PMID- 24293114
TI  - Physicochemical modulation of chitosan-based hydrogels induces different
      biological responses: interest for tissue engineering.
AB  - Polysaccharide-based hydrogels are remarkable materials for the development of
      tissue engineering strategies as they meet several critical requirements for such
      applications and they may partly mimic the extracellular matrix. Chitosan is
      widely envisioned as hydrogel in biomedical fields for its bioresorbability,
      biocompatibility, and fungistatic and bacteriostatic properties. In this study,
      we report that the modulation of the polymer concentration, the degree of
      acetylation, the gelation processes [or neutralization routes (NR)] in the
      preparation of different chitosan-based hydrogels lead to substantially and
      significantly different biological responses. We show that it is possible to tune
      the physicochemical characteristics, mechanical properties, and biological
      responses of such matrices. Physical hydrogels prepared from highly acetylated
      chitosan were softer, degraded quickly in vivo, and were not suitable for in
      vitro culture of human mesenchymal stem and progenitor derived endothelial cells.
      In contrast, for a same chitosan concentration and obtained by the same
      processing route, a low degree of acetylation chitosan hydrogel provided a more
      elastic material, better cell adhesion on its surface and tissue regeneration,
      and restored tissue neo-vascularization as well. This work offers promising and
      innovative perspectives for the design of hydrogel materials with tunable
      properties for tissue engineering and regenerative medicine.

PMID- 24293115
TI  - A new treatment to avoid severe ovarian hyperstimulation utilizing insights from
      in vitro maturation therapy.

PMID- 24293116
TI  - Immunological Mechanisms of Low and Ultra-Low Dose Cancer Chemotherapy.
AB  - Traditionally, anticancer chemotherapy has been generally considered to be
      strongly immunosuppressive. However, increasing evidence suggests that certain
      chemotherapeutic agents rely on the induction of antitumor immune responses, in
      both experimental animal models and patients with cancer. Many of these
      chemotherapeutic agents exert immunogenic effects via the induction and release
      of immunostimulatory "danger" signals from dying cancerous cells when used in low
      doses. New data suggests that several common chemotherapeutic agents may also
      display direct stimulating effects on immune cells even when applied in ultra-low
      concentrations (chemoimmunomodulation). Importantly, it is becoming clear that
      both immune effector cells and immune regulatory cells can be targeted by various
      chemotherapeutic agents to produce favorable antitumor immune responses.
      Therefore, utilizing cancer drugs to enhance host antitumor immunity should be
      considered a feasible therapeutic approach; and recent characterization of the
      immunomodulatory mechanisms of anticancer chemotherapy using both new and
      traditional cytotoxic agents suggests that combinations of these approaches with
      "classical" immunomodulatory agents could lead to a viable new therapeutic
      paradigm for the treatment of cancer. 

PMID- 24293117
TI  - Linaclotide: a review of its use in the treatment of irritable bowel syndrome
      with constipation.
AB  - Linaclotide (Constella(r)) is a synthetic 14-amino acid peptide, structurally
      related to guanylin and uroguanylin, that acts as a potent guanylate cyclase C
      receptor agonist. It is a first-in-class agent recently approved in the EU for
      the treatment of adult patients with moderate to severe irritable bowel syndrome
      with constipation (IBS-C). Linaclotide has very low oral bioavailability and acts
      locally in the gastrointestinal tract to stimulate fluid secretion, increase
      colonic transit, and reduce abdominal pain. In phase III trials, once-daily, oral
      linaclotide significantly increased compared with placebo the proportions of 12
      week abdominal pain/discomfort responders and 12-week degree-of-relief responders
      (co-primary endpoints recommended by the European Medicines Agency). Linaclotide
      also significantly increased the proportions of responders at 26 weeks compared
      with placebo, and significantly improved all abdominal symptoms and measures of
      bowel function at 12 weeks compared with placebo. In addition, linaclotide
      generally improved health-related quality of life compared with placebo.
      Linaclotide was generally well tolerated; the most common adverse event was
      diarrhoea. Thus, linaclotide is a novel and effective single agent for the
      treatment of IBS-C in adults.

PMID- 24293118
TI  - MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in
      human non-small cell lung cancer A549 cells.
AB  - PURPOSE: Curcumin, a natural phytochemical, exhibits potent anticancer
      activities. Here, we sought to determine the molecular mechanisms underlying the
      cytotoxic effects of curcumin against human non-small cell lung cancer (NSCLC)
      cells. METHODS: MTT assay and annexin-V/PI staining were used to analyze the
      effects of curcumin on the proliferation and apoptosis of A549 cells. The
      expression of microRNA-21 in curcumin-treated A549 cells was measured by
      quantitative real-time polymerase chain reaction assay. The protein level of
      phosphatase and tensin homolog (PTEN), a putative target of microRNA-21, was
      determined by Western blot analysis. Transfection of A549 cells with microRNA-21
      mimic or PTEN small interfering RNA was performed to modulate the expression of
      microRNA-21 and PTEN under the treatment of curcumin. RESULTS: Curcumin at 20-40
      MUM inhibited cell proliferation and induced apoptosis in A549 cells. Curcumin
      treatment produced a dose-dependent and significant (P < 0.05) suppression of
      microRNA-21 expression, compared to untreated A549 cells. Moreover, the protein
      level of PTEN, a putative target of microRNA-21, was significantly elevated in
      curcumin-treated A549 cells, as determined by Western blot analysis. Transfection
      of A549 cells with microRNA-21 mimic or PTEN small interfering RNA significantly
      (P < 0.05) reversed the growth suppression and apoptosis induction by curcumin,
      compared to corresponding controls. CONCLUSIONS: Our data suggest a novel
      molecular mechanism in which inhibition of microRNA-21 and upregulation of PTEN
      mediate the anticancer activities of curcumin in NSCLC cells. Suppression of
      microRNA-21 may thus have therapeutic benefits against this malignancy.

PMID- 24293119
TI  - Low brain CB1 receptor occupancy by a second generation CB1 receptor antagonist
      TM38837 in comparison with rimonabant in nonhuman primates: a PET study.
AB  - Both central and peripheral cannabinoid receptor type 1 (CB1R) have been
      considered to be among the key targets for obesity treatment. First generation
      CB1R antagonists/inverse agonists such as rimonabant and taranabant exhibited
      severe CNS side effects such as anxiety and depression, which are considered to
      be related to the compounds' ability to access central CB1R. Recently, several
      compounds have been developed as second generation antagonists with a profile of
      restriction to peripheral CB1R. We evaluated the distribution of TM38837, a
      second generation CB1R antagonist, using brain and whole body PET in three
      cynomolgus monkeys, and established the relationship between CB1R occupancy and
      dose/plasma concentration of TM38837 in comparison with rimonabant. A brain PET
      study was performed using [(11) C]MePPEP, a PET radioligand for CB1R, to evaluate
      the brain CB1R occupancy of TM38837 at various plasma concentrations in
      comparison with rimonabant at known efficacious plasma concentrations. A whole
      body PET study was performed to investigate the change of peripheral distribution
      of [(11) C]MePPEP by TM38837 administration, which indirectly estimated the
      effects to the peripheral CB1R by TM38837. CB1R occupancy by both TM38837 and
      rimonabant increased in a dose/plasma concentration-dependent manner. However, in
      vivo affinity by plasma level was more than 100 times lower for TM38837.
      Peripherally, [(11) C]MePPEP accumulation decreased in gall bladder and brown
      adipose tissue by TM38837 administration. TM38837 showed rather lower CB1R
      occupancy than rimonabant at the expected therapeutic plasma level, which is
      expected to reduce CNS side effects in clinical situations. Further clinical
      development of TM38837 is warranted.

PMID- 24293120
TI  - A telerehabilitation intervention for patients with Chronic Obstructive Pulmonary
      Disease: a randomized controlled pilot trial.
AB  - OBJECTIVE: First, to investigate the effects of a telerehabilitation intervention
      on health status and activity level of patients with Chronic Obstructive
      Pulmonary Disease (COPD), compared to usual care. Second, to investigate how
      patients comply with the intervention and whether compliance is related to
      treatment outcomes. DESIGN: a randomized controlled pilot trial SUBJECTS: Thirty
      four patients diagnosed with COPD. INTERVENTION: The telerehabilitation
      application consists of an activity coach (3D-accelerometer with smartphone) for
      ambulant activity registration and real-time feedback, complemented by a web
      portal with a symptom diary for self-treatment of exacerbations. The intervention
      group used the application for 4 weeks. The control group received usual care.
      MAIN MEASURES: Activity level measured by a pedometer (in steps/day), health
      status by the Clinical COPD Questionnaire at baseline and after intervention.
      Compliance was expressed as the time the activity coach was worn. RESULTS:
      Fourteen intervention and 16 control patients completed the study. Activity level
      (steps/day) was not significantly affected by the intervention over time. There
      was a non-significant difference in improvement in health status between the
      intervention (-0.34+/-0.55) and control group (0.02+/-0.57, p=0.10). Health
      status significantly improved within the intervention group (p=0.05). The
      activity coach was used more than prescribed (108%) and compliance was related to
      the increase in activity level for the first two feedback weeks (r=0.62, p=0.03).
      CONCLUSIONS: This pilot study shows the potential of the telerehabilitation
      intervention: compliance with the activity coach was high, which directly related
      to an improvement in activity levels.

PMID- 24293122
TI  - [EUS-guided drainage of the pancreatic duct (EUPD)--promising therapeutic
      alternative to surgical intervention in case of symptomatic retention of the
      pancreatic duct and unsuccessful ERP].
AB  - BACKGROUND: Transpapillary ERP is the gold standard in symptomatic retention of
      the pancreatic duct or pancreatic fistula; however, it fails in 5-10 % due to a
      papilla which cannot be reached or cannulated, or in postoperative changes which
      do not allow conventional endoscopic drainage. METHOD: Based on our clinical,
      endoscopic and EUS-related experience as well as a literature search, EUS-guided
      pancreaticography and drainage of the pancreatic duct (EUPD) are described as
      alternative approach i) to symptomatic retention of pancreatic duct, ii) for
      cases with stenoses of the pancreatic duct and anastomoses which cannot be
      treated with conventional endoscopy, and iii) for patients with postoperative
      pancreatic fistula within the diagnostic and therapeutic management, including
      adequate indication, performance and outcome. RESULTS: EUPD is indicated in cases
      with i) altered anatomy of upper GI tract (congenital; papilla or
      pancreaticoenteric anastomosis), ii) symptomatic retention of pancreatic duct due
      to changes in peripapillary region or iii) stenosis of pancreatic
      duct/anastomosis, and iv) if surgical intervention cannot be done with a
      reasonable risk-benefit ratio. EUPD can provide a success rate of 25 to 92 %, a
      complication rate of 14 to 40 % (bleeding, perforation, pancreatitis, pain) and
      long-term clinical success rate of 69 to 78 % (pain-, symptom-free). Advantages
      are sustained endoscopic methodological variability, minimal invasiveness,
      improvement in quality of life, possible endoscopic revision of complications and
      conventional endoscopic equipment. In contrast disadvantages include high level
      of expertise, only low case load, long learning curve, instruments needing
      further optimisation, and a still not good clinical success rate of 70 % as well
      as status as an experimental clinical method. CONCLUSION: With adequate
      experience EUPD is for carefully selected patients an uncomplicated, elegant and
      safe method and represents an alternative therapeutic option for the
      interventional endoscopist allowing more invasive procedures to be avoided.
      Further prospective and systematic evaluations and technical refinements of EUPD
      associated results are needed in order to establish general therapeutic
      guidelines on indications, peri-interventional management and to define a
      practical guideline-relevant procedure.

PMID- 24293123
TI  - Over-expression of Rap2a inhibits glioma migration and invasion by down
      regulating p-AKT.
AB  - Ras-oncogenic pathway contributes to the pathogenesis of various tumours in
      humans, in which mutations of three canonical genes including H-Ras, N-Ras and K
      Ras are the most common events. Dysregulation of Ras signalling can be
      tumourigenic, especially gliomas of the central nervous system. Rap proteins are
      members of the small GTPase superfamily that involved in many biological
      processes. However, it remains largely unclear as to whether and how Rap proteins
      are involved in the development of multiple gliomas. We found that the levels of
      the protein Rap2a and the activity of Rap2a (GTP-Rap2a) were weakly expressed in
      glioma tissues. Overexpressed Rap2a significantly inhibited the migration and
      invasion of glioma cells with an increase of GTP-Rap2a. Overexpression of the
      dominant-active (DA-Rap2a), but not the dominant-negative (DN-Rap2a) form of
      Rap2a, also similarly inhibited the migration and invasion of glioma cells by
      reducing the phosphorylation level of AKT. In contrast, downregulation of Rap2a
      promoted glioma migration and invasion, and raised the phosphorylation level of
      AKT, whereas these effects were inhibited by PI3K-specific inhibitor, LY294002.
      Thus unlike the other family members of Ras, Rab2a probably serves as a tumour
      suppressor in the pathogenesis of glioma. 

PMID- 24293121
TI  - Apolipoprotein E, gender, and Alzheimer's disease: an overlooked, but potent and
      promising interaction.
AB  - Alzheimer's disease (AD) is an increasingly prevalent, fatal neurodegenerative
      disease that has proven resistant, thus far, to all attempts to prevent it,
      forestall it, or slow its progression. The epsilon4 allele of the Apolipoprotein
      E gene (APOE4) is a potent genetic risk factor for sporadic and late-onset
      familial AD. While the link between APOE4 and AD is strong, many expected
      effects, like increasing the risk of conversion from MCI to AD, have not been
      widely replicable. One critical, and commonly overlooked, feature of the APOE4
      link to AD is that several lines of evidence suggest it is far more pronounced in
      women than in men. Here we review previous literature on the APOE4 by gender
      interaction with a particular focus on imaging-related studies. 

PMID- 24293124
TI  - Head and brain response to blast using sagittal and transverse finite element
      models.
AB  - Mild traumatic brain injury caused by blast exposure from Improvised Explosive
      Devices has become increasingly prevalent in modern conflicts. To investigate
      head kinematics and brain tissue response in blast scenarios, two solid
      hexahedral blast-head models were developed in the sagittal and transverse
      planes. The models were coupled to an Arbitrary Lagrangian-Eulerian model of the
      surrounding air to model blast-head interaction, for three blast load cases (5 kg
      C4 at 3, 3.5 and 4 m). The models were validated using experimental kinematic
      data, where predicted accelerations were in good agreement with experimental
      tests, and intracranial pressure traces at four locations in the brain, where the
      models provided good predictions for frontal, temporal and parietal, but
      underpredicted pressures at the occipital location. Brain tissue response was
      investigated for the wide range of constitutive properties available. The models
      predicted relatively low peak principal brain tissue strains from 0.035 to 0.087;
      however, strain rates ranged from 225 to 571 s-1. Importantly, these models have
      allowed us to quantify expected strains and strain rates experienced in brain
      tissue, which can be used to guide future material characterization. These
      computationally efficient and predictive models can be used to evaluate
      protection and mitigation strategies in future analysis.

PMID- 24293125
TI  - Faith-based perspectives on the use of chimeric organisms for medical research.
AB  - Efforts to advance our understanding of neurodegenerative diseases involve the
      creation chimeric organisms from human neural stem cells and primate embryos-
      known as prenatal chimeras. The existence of potential mentally complex beings
      with human and non-human neural apparatus raises fundamental questions as to the
      ethical permissibility of chimeric research and the moral status of the creatures
      it creates. Even as bioethicists find fewer reasons to be troubled by most types
      of chimeric organisms, social attitudes towards the non-human world are often
      influenced by religious beliefs. In this paper scholars representing eight major
      religious traditions provide a brief commentary on a hypothetical case concerning
      the development and use of prenatal human-animal chimeric primates in medical
      research. These commentaries reflect the plurality and complexity within and
      between religious discourses of our relationships with other species. Views on
      the moral status and permissibility of research on neural human animal chimeras
      vary. The authors provide an introduction to those who seek a better
      understanding of how faith-based perspectives might enter into biomedical ethics
      and public discourse towards forms of biomedical research that involves chimeric
      organisms.

PMID- 24293126
TI  - A novel mouse model for Down syndrome that harbor a single copy of human
      artificial chromosome (HAC) carrying a limited number of genes from human
      chromosome 21.
AB  - Down syndrome (DS), also known as Trisomy 21, is the most common chromosome
      aneuploidy in live-born children and displays a complicated symptom. To date,
      several kinds of mouse models have been generated to understand the molecular
      pathology of DS, yet the gene dosage effects and gene(s)-phenotype(s) correlation
      are not well understood. In this study, we established a novel method to generate
      a partial trisomy mice using the mouse ES cells that harbor a single copy of
      human artificial chromosome (HAC), into which a small human DNA segment
      containing human chromosome 21 genes cloned in a bacterial artificial chromosome
      (BAC) was recombined. The produced mice were found to maintain the HAC carrying
      human genes as a mini-chromosome, hence termed as a Trans-Mini-Chromosomal (TMC)
      mouse, and HAC was transmitted for more than twenty generations independent from
      endogenous mouse chromosomes. The three human transgenes including cystathionine
      beta-synthase, U2 auxiliary factor and crystalline alpha A were expressed in
      several mouse tissues with various expression levels relative to mouse endogenous
      genes. The novel system is applicable to any of human and/or mouse BAC clones.
      Thus, the TMC mouse carrying a HAC with a limited number of genes would provide a
      novel tool for studying gene dosage effects involved in the DS molecular
      pathogenesis and the gene(s)-phenotype(s) correlation. 

PMID- 24293127
TI  - Construction and identification of a cDNA library for use in the yeast two-hybrid
      system from duck embryonic fibroblast cells post-infected with duck enteritis
      virus.
AB  - To explore and isolate genes related to duck embryonic fibroblast cells (DEFs)
      post-infected with duck enteritis virus (DEV), a cDNA library was established
      using SMART (Switching Mechanism At 5' end of the RNA Transcript) technique
      coupling with a homologous recombination method. The cells were harvested and
      total RNA was extracted at 48 h post infection. Then the mRNAs were purified and
      reverse transcribed to first-strand cDNAs using oligo (dT) primers (CDS III).
      Subsequently, long distance-PCR was performed, the double-stranded cDNAs were
      purified, and a transformation assay was carried out in that order. Eventually, a
      high qualitative library was successfully established according to an evaluation
      on quality. The transformation efficiency was about 2.33 * 10(6)
      transformants/4.34 MUg pGADT7-Rec (>1.0 * 10(6)). The cell density of the library
      was 1.75 * 10(9) cells/mL (>2 * 10(7) cells/mL). The titer of the primary cDNA
      library and amplified cDNA library was 6.75 * 10(5) and 2.33 * 10(7) CFU/mL
      respectively. The numbers for the primary cDNA library and amplified cDNA library
      were 1.01 * 10(7) and 1.14 * 10(9), respectively, and the recombinant rate was
      97.14 %. The sequence results of 27 randomly picked independent clones revealed
      the insert ranged from 0.323 to 2.017 kb with an average insert size of 0.807 kb.
      Full-length transcripts of DEV-CHv LORF3, UL26 and UL35 genes were acquired
      through sequence similarity analysis from the non-redundant nucleic acid or
      protein database. Five polyA sites were identified in the DEV-CHv genome. Also, a
      new transcript of 668 bp was found between the IRS gene and US1 gene of the DEV
      CHv genome. Thus, we concluded that the constructed cDNA library will be a useful
      tool in proteomic analysis of interactions between the DEV and host DEFs, and
      discovery of biomarkers studies on the mechanism of DEV and subsequently
      exploitation original vaccines and antiviral drugs to prevent or cure diseases.

PMID- 24293128
TI  - A trehalose-6-phosphate synthase gene from Saccharina japonica (Laminariales,
      Phaeophyceae).
AB  - The full-length cDNA sequence of a trehalose-6-phosphate synthase gene from
      Saccharina japonica (designated as SjaTPS) (Accession: KC578568) was isolated
      based on homologous cloning and RACE-PCR. It was 4,127 bp, with 320 bp 5'-UTR, 21
      bp 3'-UTR, and open reading frame (ORF) of 3,786 bp. The deduced 1,261 amino
      acids characterized with predicted molecular weight of 137.84 kDa and theoretical
      isoelectric point of 7.12. The SjaTPS had one N-terminal CBM20 (family 20
      carbohydrate-binding module) domain, one TPS domain (trehalose-6-phosphate
      synthase) in the middle region and a single TPP (trehalose-6-phosphate
      phosphatase) domain near the C-terminus. Structural analysis suggested that the
      SjaTPS putatively functioned as trehalose-6-phosphate synthase, and might be
      related to laminaran metabolism in S. japonica. Homology analysis indicated that
      the SjaTPS shared 49-70 % similarities with the 13 known TPS sequences of other
      algae; only 55 % amino acid similarities were detected between SjaTPS and the
      previously reported TPS sequence of S. japonica (Accession: DQ666325).
      Phylogenetic analysis revealed close affinity between SjaTPS and TPS of brown
      alga Ectocarpus siliculosus (Accession: CBJ29609). Transcriptional analysis
      showed that desiccation greatly enhanced SjaTPS expression and the maximum
      appeared at 3 h, which was about 300-fold compared to that of the start, implied
      that SjaTPS was involved with drought adaption in kelp. In vitro expression of
      SjaTPS showed that one distinct band existed at ~115 kDa, and western blot
      detection proved that it was positive to the anti-His antibody with high
      specificity. Our results increased the knowledge of trehalose-6-phosphate
      synthase properties in S. japonica and also important for better understanding
      the role trehalose plays in kelp abiotic tolerance for adaption to the
      sublittoral habitats.

PMID- 24293129
TI  - Using cryoEM reconstruction and phase extension to determine crystal structure of
      bacteriophage phi6 major capsid protein.
AB  - Bacteriophage phi6 is a double-stranded RNA virus that has been extensively
      studied as a model organism. Here we describe structure determination of phi6
      major capsid protein P1. The protein crystallized in base centered orthorhombic
      space group C2221. Matthews's coefficient indicated that the crystals contain
      from four to seven P1 subunits in the crystallographic asymmetric unit. The self
      rotation function had shown presence of fivefold axes of non-crystallographic
      symmetry in the crystals. Thus, electron density map corresponding to a P1
      pentamer was excised from a previously determined cryoEM reconstruction of the
      phi6 procapsid at 7 A resolution and used as a model for molecular replacement.
      The phases for reflections at higher than 7 A resolution were obtained by phase
      extension employing the fivefold non-crystallographic symmetry present in the
      crystal. The averaged 3.6 A-resolution electron density map was of sufficient
      quality to allow model building. 

PMID- 24293130
TI  - Sensitive determination of the potential biomarker sarcosine for prostate cancer
      by LC-MS with N,N'-dicyclohexylcarbodiimide derivatization.
AB  - Sarcosine, a potential biomarker of prostate cancer, has drawn great attention in
      recent years. However, controversial research keeps arising about its role as a
      biomarker that might come from the two isomers (alpha-alanine and beta-alanine)
      of sarcosine due to their same molecular weight and similar properties, which
      could interfere with the accurate detection of sarcosine. In this study, a simple
      and sensitive method was developed for the detection of sarcosine and the two
      isomers by LC with ion-trap MS through a novel derivatization reagent N,N'
      dicyclohexylcarbodiimide. N,N'-Dicyclohexylcarbodiimide is usually considered as
      a condensation reagent, however, it was directly used as a derivatization reagent
      through a rearrangement side reaction in this study. The proposed method not only
      improved the chromatographic retention behavior of sarcosine and its two isomers,
      which was a benefit to their separation, but also dramatically enhanced the
      detection sensitivity of sarcosine, which was more favorable for real sample
      analysis. The factors affecting the productivity of the derivatization reaction,
      such as reaction time and amount of derivatization reagent, were systematically
      optimized. The method shows good linearity (R(2) > 0.99), sensitivity with LODs
      of sarcosine as low as 1 ng/mL, and repeatability with the RSD < 6.07%. The
      developed method was applied to the analysis of urine. 

PMID- 24293131
TI  - The INITIATOR study: pilot data on real-world clinical and economic outcomes in
      US patients with type 2 diabetes initiating injectable therapy.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) progression often results in
      treatment intensification with injectable therapy to maintain glycemic control.
      Using pilot data from the Initiation of New Injectable Treatment Introduced after
      Anti-diabetic Therapy with Oral-only Regimens study, real-world treatment
      patterns among T2DM patients initiating injectable therapy with insulin glargine
      or liraglutide were assessed. METHODS: This was a retrospective analysis of
      claims from the OptumInsightTM (OI; January 1, 2010 to July 30, 2010) and
      HealthCore((r)) (HC; January 1, 2010 to June 1, 2010) health insurance databases.
      Baseline characteristics, health care resource utilization, and costs were
      compared between adults with T2DM initiating injectable therapy with insulin
      glargine pen versus liraglutide. Follow-up outcomes, including glycated
      hemoglobin A1c (A1C), hypoglycemia, health care utilization, and costs, were
      assessed. RESULTS: At baseline, almost one in three liraglutide patients (OI, n =
      363; HC, n = 521) had A1C <7.0%, while insulin glargine patients (OI, n = 498;
      HC, n = 1,188) had poorer health status, higher A1C (insulin glargine: 9.8% and
      9.1% versus liraglutide: 7.9% and 7.7%, OI and HC, respectively, both P < 0.001),
      and were less likely to be obese (insulin glargine: 10.8% and 9.2% versus
      liraglutide: 17.4% and 18.8%, OI and HC, respectively, both P < 0.01). The
      percentage of patients experiencing a hypoglycemic event was numerically higher
      for insulin pen use for both cohorts (OI 4.4% versus 3.0%; HC 6.2% versus 2.3%).
      During follow-up, in the insulin glargine cohort, annualized diabetes-related
      costs remained unchanged ($8,344 versus $7,749 OI, and $7,094 versus $7,731 HC),
      despite a significant increase in pharmacy costs, due to non-significant
      decreases in medical costs, while the liraglutide cohort had a significant
      increase in annualized diabetes-related costs ($4,510 versus $7,731 OI, and
      $4,136 versus $7,111 HC; both P < 0.001) due to a non-significant increase in
      medical costs coupled with a significant increase in pharmacy costs. CONCLUSION:
      These descriptive data identified differences in demographic and baseline
      clinical characteristics among patients initiating injectable therapies. The
      different health care utilization and cost patterns warrant further cost
      effectiveness analysis.

PMID- 24293133
TI  - Simeprevir: first global approval.
AB  - Simeprevir (Sovriad(TM)) is a new direct-acting antiviral drug and a second
      generation small-molecule NS3/4A serine protease inhibitor developed by Janssen
      and Medivir for the oral treatment of adults with genotype 1 and/or genotype 4
      chronic hepatitis C virus (HCV) infection (chronic hepatitis C). Simeprevir
      antiviral activity is achieved by its non-covalent binding to HCV protease, with
      a fast association and slow dissociation rate. The capsule formulation is
      approved in Japan and Canada for use in combination with pegylated interferon
      (peginterferon) and ribavirin for genotype 1 chronic hepatitis C, and has been
      filed for approval in the US in this indication. In addition, the capsule
      formulation has been filed for approval in the EU for use in combination with
      peginterferon and ribavirin for genotype 1 and 4 chronic hepatitis C. Phase III
      trials of the capsule formulation of simeprevir are underway in several other
      regions, including China. In the pivotal phase III trials, simeprevir was
      administered once daily for 12 weeks in combination with peginterferon and
      ribavirin for 24 or 48 weeks. This article summarizes the milestones in the
      development of simeprevir leading to this first approval for chronic hepatitis C.

PMID- 24293132
TI  - The fixed-dose combination of olmesartan/amlodipine was superior in central
      aortic blood pressure reduction compared with perindopril/amlodipine: a
      randomized, double-blind trial in patients with hypertension.
AB  - INTRODUCTION: Central blood pressure (BP), an important measure of cardiovascular
      risk, has been shown to be effectively reduced by calcium channel blockade with
      amlodipine (AML) plus renin-angiotensin system blockade by the angiotensin
      converting enzyme inhibitor, perindopril (PER). The aim of the SEVITENSION study
      was to compare the central effects of PER/AML against renin-angiotensin system
      blockade with the angiotensin II receptor blocker olmesartan (OLM) plus AML.
      METHODS: In this multicenter, parallel group, non-inferiority study, patients
      received AML 10 mg during a 2- to 4-week run-in before randomization to 24 weeks
      of double-blind treatment with the fixed-dose combination of OLM/AML 40/10 mg or
      PER/AML 8/10 mg. Hydrochlorothiazide was added at Weeks 4, 8, or 12 in patients
      with inadequate BP control. The primary efficacy variable was the absolute change
      in central systolic BP (CSBP) from baseline to the final examination, measured by
      radial artery applanation tonometry and analyzed by parametric analysis of
      covariance. Secondary variables included 24-h ambulatory and seated BP
      measurements as well as BP normalization. RESULTS: Of 600 patients enrolled, 486
      were randomized (244 to OLM/AML 40/10 mg, 242 to PER/AML 8/10 mg). The reduction
      in CSBP was larger with OLM/AML (14.5 +/- 0.83 mmHg) than with PER/AML (10.4 +/-
      0.84 mmHg). The between-group difference was -4.2 +/- 1.18 mmHg with 95%
      confidence intervals (-6.48 to -1.83 mmHg) within the predefined non-inferiority
      margin (2 mmHg). An integrated superiority test confirmed that OLM/AML was
      superior to PER/AML (p < 0.0001) in reducing CSBP. The superiority of OLM/AML
      over PER/AML was also established for the majority of secondary efficacy
      variables; at the final examination, 75.6% of OLM/AML recipients achieved BP
      normalization (mean seated systolic BP/diastolic BP <140/90 mmHg) compared with
      57.5% of PER/AML recipients (p < 0.0001). CONCLUSION: The combination of OLM/AML
      was superior to PER/AML in reducing CSBP and other efficacy measures, including a
      significantly higher rate of BP normalization.

PMID- 24293134
TI  - Development of purely structure-based pharmacophores for the topoisomerase I-DNA
      ligand binding pocket.
AB  - Purely structure-based pharmacophores (SBPs) are an alternative method to ligand
      based approaches and have the advantage of describing the entire interaction
      capability of a binding pocket. Here, we present the development of SBPs for
      topoisomerase I, an anticancer target with an unusual ligand binding pocket
      consisting of protein and DNA atoms. Different approaches to cluster and select
      pharmacophore features are investigated, including hierarchical clustering and
      energy calculations. In addition, the performance of SBPs is evaluated
      retrospectively and compared to the performance of ligand- and complex-based
      pharmacophores. SBPs emerge as a valid method in virtual screening and a
      complementary approach to ligand-focussed methods. The study further reveals that
      the choice of pharmacophore feature clustering and selection methods has a large
      impact on the virtual screening hit lists. A prospective application of the SBPs
      in virtual screening reveals that they can be used successfully to identify novel
      topoisomerase inhibitors. 

PMID- 24293135
TI  - Fascinating interaction between host and pathogen.
AB  - Clinical manifestations of disease depend upon host's immune response that is
      induced by pathogen and modified by the host's innate and adaptive immunity.
      Immunocompetent children of similar age and nutrition evoke different responses
      to the same pathogen varying from benign to potentially fatal condition. This
      results in diverse clinical presentations of a disease, that is different from
      the standard expected pattern and thus, poses a diagnostic challenge. Even,
      subsequent progression of a disease is also variable. It is the balance between
      immune stimulation, immune suppression and immune tolerance that decides the
      outcome. In case of balanced response, child recovers completely without any
      damage. However at times, cure is at the expense of permanent sequalae while in
      case of unfavourable immune response, survival may not be certain inspite of
      successful therapy. Symptoms and physical signs of primary disease often overlap
      with those caused by host's immune response. In such a situation, it is difficult
      to decide whether therapy of primary disease has failed due to drug resistance or
      whether persistence or deterioration is the result of immune response.
      Occasionally pathogen can transform into "superantigen" that may lead to
      "cytokine storm". Resulting immune-mediated complications may endanger life and
      at best, treated symptomatically. Immune suppressive drugs such as steroids,
      chemotherapeutic agents, IVIG or specific antibodies may not be able to suppress
      undesirable immune response. It is not just the immune suppression that is
      required but ideally immune modulation. Immune modulation refers to enhancing
      protective responses while avoiding destructive ones. At present, science falls
      short of anticipating harmful immune responses and lacks specific immune
      intervention.Laboratory test results are also dependent on host response and
      hence need cautious interpretation based on clinical profile in consideration
      with multiple variables. In final analysis, fight between host and pathogen is a
      complex one and often unpredictable. It is hoped that most children evoke
      favourable response but pediatrician has to be watchful even in the most benign
      disease. 

PMID- 24293136
TI  - Loss of Bcl-2 expression correlates with increasing sensitivity to apoptosis in
      differentiating ES cells.
AB  - Embryonic stem (ES) cells are derived from the inner cell mass of blastocysts and
      have a pluripotency to differentiate into a variety of cell types. ES cells have
      high resistance to environmental stress compared to functional cells, which can
      undergo apoptosis when stressed. We have investigated whether ES cells have
      resistance to multiple types of stress or selective stress. Phytosphingosine
      (PHS) and staurosporine (STS) were used as chemical stressors. PHS induced
      mitochondria-mediated apoptosis in several cell lines. STS is a protein kinase
      inhibitor that induces apoptosis even without mitochondrial involvement. PHS
      treatment damaged 3T3 mouse fibroblasts, but did not damage ES cells. STS damaged
      ES cells as well as 3T3 mouse fibroblasts at similar doses. Susceptibility to
      cell damage is correlated with the retention of the mitochondrial membrane
      potential. PHS treatment could induce DNA fragmentation in differentiated ES
      cells. Differences in cell-death susceptibility between the undifferentiated and
      differentiated states showed that the mitochondria-localised anti-apoptotic
      protein Bcl-2 was highly expressed in undifferentiated ES cells, which gradually
      decreased during differentiation. These results suggest that undifferentiated
      mouse ES cells have a high resistance to mitochondria-involved extracellular
      stress. 

PMID- 24293137
TI  - GC models for separation optimization in pressure-tunable tandem capillary
      columns operated isothermally: part 2: control experiments using a new capillary
      column interface.
AB  - In the previous part of this study, a significant improvement of the fundamental
      relationships that control GC resolution in a pressure-tunable assembly operating
      in isothermal conditions inside a single oven was made. A theoretical approach
      for the correct choice of the working temperature was proposed for the first
      time. In this second part of our report, a new interfacing device has been
      proposed for a rapid and reliable alignment of the two columns at the midpoint
      junction. Moreover, the results of a series of experimental tests have confirmed
      the validity of the proposed mathematical models. 

PMID- 24293138
TI  - Predictive models of resting state networks for assessment of altered functional
      connectivity in mild cognitive impairment.
AB  - Due to the difficulties in establishing correspondences between functional
      regions across individuals and populations, systematic elucidation of functional
      connectivity alterations in mild cognitive impairment (MCI) in comparison with
      normal controls (NC) is still a challenging problem. In this paper, we assessed
      the functional connectivity alterations in MCI via novel, alternative predictive
      models of resting state networks (RSNs) learned from multimodal resting state
      fMRI (R-fMRI) and diffusion tensor imaging (DTI) data. First, ICA-clustering was
      used to construct RSNs from R-fMRI data in NC group. Second, since the RSNs in
      MCI are already altered and can hardly be constructed directly from R-fMRI data,
      structural landmarks derived from DTI data were employed as the predictive models
      of RSNs for MCI. Third, given that the landmarks are structurally consistent and
      correspondent across NC and MCI, functional connectivities in MCI were assessed
      based on the predicted RSNs and compared with those in NC. Experimental results
      demonstrated that the predictive models of RSNs based on multimodal R-fMRI and
      DTI data systematically and comprehensively revealed widespread functional
      connectivity alterations in MCI in comparison with NC. 

PMID- 24293140
TI  - Flow-mediated dilatation (FMD) and prevalence of cardiovascular risk factors: the
      value of FMD assessment in high risk patients is limited.
AB  - BACKGROUND: Since flow-mediated dilatation (FMD) is influenced by different
      factors, its clinical usefulness and validation is widely discussed. AIM: To
      assess the major factors that determine FMD values in a wide range of subjects
      with and without cardiovascular (CV) risk factors/diseases (CVRF/CVD). METHODS
      AND RESULTS: 617 consecutive patients (mean age: 50.1 +/- 14.9 years, males:
      349/56.5%) hospitalised between 2005 and 2011 were enrolled into the study.
      Demographic data and CVRF/CVD with a significant impact on FMD values were
      analysed: hyperlipidaemia, active smoking, arterial hypertension, coronary artery
      disease, diabetes mellitus and heart valve disease. The population was divided
      depending on the number of coexisting CVRF/CVD (0-, 1-, 2-, 3-, 4-, 5-CVRF/CVD
      groups). The median FMD value in the entire group of patients was 10% (5-17). An
      analysis of the FMD percentage in particular groups showed significantly higher
      FMD values in patients without any CVRF/CVD (group 0), as well as in patients
      with one coexisting CVRF/CVD (group 1) compared to the other groups. The presence
      of two or more CVRF/CVD was not associated with a significantly higher FMD
      reduction. The analysis of patients with only one CVRF/CVD revealed the lowest
      FMD values in patients with coronary artery disease. CONCLUSIONS: FMD is related
      to the number of traditional CVRF/CVDs; however, coronary artery disease has the
      most significant influence on FMD decrease among analysed factors. The value of
      FMD assessment in high risk patients is limited.

PMID- 24293139
TI  - Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response
      to microbiota and proinflammatory cytokines increases IL-23p19 expression.
AB  - Commensal flora plays an important role in the development of the mucosal immune
      system and in maintaining intestinal homeostasis. However, the mechanisms
      involved in regulation of host-microbiota interaction are still not completely
      understood. In this study, we examined how microbiota and intestinal inflammatory
      conditions regulate host microRNA expression and observed lower microRNA-107 (miR
      107) expression in the inflamed intestines of colitic mice, compared with that in
      normal control mice. miR-107 was predominantly reduced in epithelial cells and
      CD11c(+) myeloid cells including dendritic cells and macrophages in the inflamed
      intestines. We demonstrate that IL-6, IFN-gamma, and TNF-alpha downregulated,
      whereas TGF-beta promoted, miR-107 expression. In addition, miR-107 expression
      was higher in the intestines of germ-free mice than in mice housed under specific
      pathogen-free conditions, and the presence of microbiota downregulated miR-107
      expression in DCs and macrophages in a MyD88- and NF-kappaB-dependent manner. We
      determined that the ectopic expression of miR-107 specifically repressed the
      expression of IL-23p19, a key molecule in innate immune responses to commensal
      bacteria. We concluded that regulation of miR-107 by intestinal microbiota and
      proinflammatory cytokine serve as an important pathway for maintaining intestinal
      homeostasis. 

PMID- 24293141
TI  - Comparison between optical coherence tomography and intravascular ultrasound in
      detecting neointimal healing patterns after stent implantation.
AB  - BACKGROUND: The amount of data comparing intravascular ultrasound (IVUS) and
      optical coherence tomography (OCT) for the detection of stent coverage in
      clinical settings is limited. AIM: To make a qualitative and quantitative
      assessment of the vascular healing patterns in patients after stent implantations
      visualised by both IVUS and OCT. METHODS: Images were obtained in patients with
      clinical symptoms of angina, who had had a bare metal stent implanted in the
      previous 12 months. Angiography, IVUS and OCT were performed in 14 coronary
      arteries. Measurements of stent, lumen and neo-intima areas and dimensions were
      performed in stented regions and in both 10 mm references. IVUS, OCT, and
      angiographic data were compared in matched regions. Off-line analyses were
      performed by an independent core lab. RESULTS: 14 stents were imaged without any
      procedural complications. The nominal stent length was 28 +/- 4.5 mm. OCT was the
      most accurate technique for assessing stent length (28.12 +/- 6.8 mm), while QCA
      underestimated length due to foreshortening (22.16 +/- 6.39 mm) and IVUS was
      vulnerable to random error due to discontinuous pullbacks and vessel movements
      (24.21 +/- 7.90 mm). Minimum lumen area (MLA) and minimum lumen diameter (MLD) in
      reference sites were comparable in IVUS and OCT, whereas there were significant
      differences between these two modalities for MLA (3.30 +/- 1.49 vs. 2.19 +/- 1.30
      mm2, p = 0.0046) and for MLD (2.42 +/- 0.51 vs. 1.58 +/- 0.56 mm2, p = 0.0023) in
      stented segments. There was a slight overestimation of lumen volume (130.18 +/-
      70.61 vs. 117.82 +/- 67.02 mm3, p = 0.7256),a marked overestimation of stent
      volume (179.29 +/- 97.58 vs. 226.46 +/- 108.76 mm3, p = 0.0544) and a
      statistically significant difference in the neointima volume (49.11 +/- 39.70 vs.
      108.64 +/- 43.77 mm3, p = 0.0060) by IVUS compared to OCT. Mean neointima burden
      in IVUS was much smaller than in OCT (20.79 +/- 14.27% vs. 58.16 +/- 18.25%, p =
      0.0033). CONCLUSIONS: OCT can precisely quantify struts coverage and is more
      accurate than IVUS in the assessment of vascular healing in patients after stent
      implantation.

PMID- 24293142
TI  - Translation and cultural adaptation of a Patient Perception of Arrhythmia
      Questionnaire in Poland.
AB  - BACKGROUND: The Patient Perception of Arrhythmia Questionnaire (PPAQ) is a
      disease-specific questionnaire designed to measure symptoms and health-related
      quality of life in patients suffering from a group of arrhythmias collectively
      known as supraventricular tachycardias (SVT). There is no valid translation of
      PPAQ available in Poland, which hinders research in this area with Polish
      arrhythmia patients. AIM: To conduct initial content validity testing through
      translation and cultural adaptation of the English language version of the PPAQ
      to the Polish language. METHODS: The whole project was conducted according to the
      ISPOR Principles of Good Practice for the Translation and Cultural Adaptation
      Process for Patient-Reported Outcomes (PRO) Measures published in 2005. RESULTS:
      In 2011, the PPAQ was translated into Polish and cultural adaptation was
      performed on 20 patients with SVT (12 male, age 54.9 +/- 17.4). Issues concerning
      the exact meanings of symptom names and language-dependant gender-related
      distinctions were identified. The former was solved by cooperation with experts
      in arrhythmia, and the latter by incorporating patients' preferences during
      cognitive debriefing. CONCLUSIONS: The Polish translation was well accepted by
      patients during this translation and initial content validity testing. Issues
      arising during the translation process may recur in other translations and be
      resolved in a similar manner.

PMID- 24293143
TI  - Inflammatory activity of pericoronary adipose tissue may affect plaque
      composition in patients with acute coronary syndrome without persistent ST
      segment elevation: preliminary results.
AB  - BACKGROUND: The extravascular expression of inflammatory mediators may adversely
      influence coronary lesion formation and plaque stability through outside-to
      inside signalling. It has been shown that the maximal standardised uptake value
      (SUV) of 18-fluorodeoxyglucose detected by positron emission tomography (PET/CT)
      is proportional to macrophage density. AIM: To investigate whether the
      inflammatory activity of pericoronary adipose tissue (PVAT) may influence plaque
      composition in acute coronary syndrome without persistent ST-segment elevation
      (NSTE-ACS) patients. METHODS: In a prospective study, 36 coronary arteries (LM,
      RCA, LCX, LAD) were investigated in non-diabetic patients with a low or
      intermediate risk of NSTE-ACS (GRACE <= 140). SUV was measured in fat surrounding
      coronary arteries on the sections corresponding to proximal and medial segments
      (Siemens biograph 64-PET/CT system). Additionally, SUV was measured in
      subcutaneous fat (SC), visceral thoracic fat (VS), and epicardial fat over the
      right ventricle (EPI). Virtual histology intravascular ultrasound (VH-IVUS) was
      performed to assess plaque composition (Volcano, USA). PET/CT sections were
      further examined in segments corresponding to coronary plaques. RESULTS: PVAT SUV
      in NSTE-ACS patients was significantly greater than in other fat locations (LM
      SUV: 1.60; RCA SUV: 1.54; LCX SUV: 1.94; LAD SUV: 2.37 vs. SC SUV: 0.57; VS SUV:
      0.77; EPI SUV: 0.98; p < 0.001; ANOVA). PVAT SUV positively correlated with
      plaque burden (r = 0.49, p < 0.05) and necrotic core plaque rate (r = 0.68, p <
      0.05), and negatively correlated with fibrous plaque rate (r = -0.52, p < 0.05).
      CONCLUSIONS: The inflammatory activity of PVAT reflected by SUV is greater than
      in subcutaneous, visceral thoracic, or epicardial tissue in NSTE-ACS patients;
      PVAT SUV correlates with the plaque burden and necrotic core component of
      coronary plaque.

PMID- 24293145
TI  - Relationship between epicardial fat and coronary microvascular dysfunction.
AB  - BACKGROUND: Coronary microvascular dysfunction (CMVD) is often suggested in
      patients with typical chest pain and abnormal stress test results that are
      indicative of myocardial ischaemia, in whom coronary angiography fails to show
      fixed stenosis inepicardial coronary arteries. The efficacy of pharmacologic
      treatment on clinical outcome remains to be determined. AIM: To determine the
      relationship between CMVD and epicardial fat thickness (EFT). METHODS: A case
      controlled study was conducted on 124 patients, aged 40-91 years. A matched set
      of 62 symptomatic and 62 asymptomatic patients underwent an exercise
      electrocardiogram and transthoracic echocardiography. Coronary angiography was
      performed in patients with abnormal exercise test results. Patients without
      coronary artery disease were considered for the study. EFT was measured by
      transthoracic echocardiography in all patients. RESULTS: EFT was significantly
      higher in patients with positive exercise test results (but normal epicardial
      coronary arteries) compared to patients with negative exercise test results (p <
      0.001). Additionally, the HDL-cholesterol level was significantly lower in
      patients with positive exercise test results (but normal epicardial coronary
      arteries) compared to patients with negative exercise test results (p < 0.0001).
      CONCLUSIONS: Patients with increased EFT are at an increased risk for developing
      angina, recurrent hospitalisation and adverse outcomes, even with normal
      epicardial coronary arteries.

PMID- 24293146
TI  - Cardiac magnetic resonance feature tracking: a novel method to assess myocardial
      strain. Comparison with echocardiographic speckle tracking in healthy volunteers
      and in patients with left ventricular hypertrophy.
AB  - BACKGROUND: Left ventricular longitudinal strain (LV-LS) and strain rate (SR) are
      sensitive markers of early systolic dysfunction. AIM: To evaluate the feasibility
      of a novel, cardiac magnetic resonance (CMR) based method known as feature
      tracking (FT) for the assessment of strain and SR, and to compare the CMR based
      results to those obtained on standard transthoracic echocardiography (TTE) in
      healthy volunteers and in patients with left ventricular hypertrophy
      cardiomyopathy (HCM). METHODS: Overall, 20 healthy volunteers (ten male, mean age
      24 +/- 3 years) and 20 consecutive patients with HCM (12 male, mean age 47 +/- 19
      years) were included. Longitudinal and circumferential strain and SR of the left
      ventricle were measured on CMR at 1.5 Tesla and TTE and interobserver variability
      was assessed. RESULTS: FT measurements were feasible in all subjects. A good
      agreement between global LV-LS measured on CMR (controls: 20.8 +/- 3.0; HCM: 17.6
      +/- 3.8) and TTE (controls: 19.4 +/- 2.1; HCM: 16.6 +/- 2.9) was found, while the
      agreement was worse for circumferential strain and all SR measurements. For the
      left and right ventricles, interobserver reproducibility was higher for strain
      measurements compared to SR. Coefficients of variation were lowest for LV-LS
      (13.2%) by CMR. CONCLUSIONS: FT analysis is a novel CMR based method for the
      analysis of myocardial strain and SR that is simple and correlates well with the
      echocardiographic measurements. Since CMR is unaffected by inadequate acoustic
      windows, FT may represent an attractive alternative to echocardiography in
      assessing the increasingly important parameters of myocardial deformation.

PMID- 24293144
TI  - Drug-eluting stents compared to bare-metal stents improve short-term survival in
      patients with acute myocardial infarction undergoing primary percutaneous
      coronary intervention: a nationwide prospective analysis of the AMIS Plus
      registry.
AB  - BACKGROUND: Recently, it has been suggested that the type of stent used in
      primary percutaneous coronary interventions (pPCI) might impact upon the outcomes
      of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents
      (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS).
      Moreover, the later generation DES, due to its biocompatible polymer coatings and
      stent design, allows for greater deliverability, improved endothelial healing and
      therefore less restenosis and thrombus generation. However, data on the safety
      and performance of DES in large cohorts of AMI is still limited. AIM: To compare
      the early outcome of DES vs. BMS in AMI patients. METHODS: This was a
      prospective, multicentre analysis containing patients from 64 hospitals in
      Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint
      was in-hospital all-cause death, whereas the secondary endpoint included a
      composite measure of major adverse cardiac and cerebrovascular events (MACCE) of
      death, reinfarction, and cerebrovascular event. RESULTS: Of 20,464 patients with
      a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were
      referred for pPCI and 13,442 received stent implantation. 10,094 patients were
      implanted with DES and 2,260 with BMS. The overall in-hospital mortality was
      significantly lower in patients with DES compared to those with BMS implantation
      (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly
      lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all
      confounding covariables, DES remained an independent predictor for lower in
      hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed
      as regards to baseline characteristics and pharmacological treatment, we
      performed a propensity score matching (PSM) to limit potential biases. Even after
      the PSM, DES implantation remained independently associated with a reduced risk
      of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001).
      CONCLUSIONS: In unselected patients from a nationwide, real-world cohort, we
      found DES, compared to BMS, was associated with lower in-hospital mortality and
      MACCE. The identification of optimal treatment strategies of patients with AMI
      needs further randomised evaluation; however, our findings suggest a potential
      benefit with DES.

PMID- 24293147
TI  - Hybrid cardiovascular procedures in the treatment of selected congenital heart
      disease in children: a single-centre experience.
AB  - BACKGROUND: Paediatric hybrid cardiovascular procedures are becoming increasingly
      popular due to the wide spectrum of cardiovascular abnormalities and a large
      population of patients who could benefit from hybrid therapy. Contemporary hybrid
      procedures are introduced in the settings where routine cardiac surgery or
      cardiac interventions would not allow satisfactory results. Combining cardiac
      surgery and interventional cardiology techniques appears more beneficial and less
      invasive for the patient. AIM: To present results of hybrid procedures performed
      in the treatment of selected congenital heart disease in our centre in 2008-2013.
      METHODS: We retrospectively analysed consecutive 80 patients referred for hybrid
      procedures. RESULTS: Overall, 73 patients survived, with 4 early and 3 late
      deaths. CONCLUSIONS: Hybrid procedures in children with congenital heart disease
      combine the experience of cardiac surgery and interventional cardiology. Hybrid
      treatment is an alternative option for selected borderline patients. Initial
      results of hybrid treatment encourage further development of these methods and
      strategies to provide optimal benefits for the patients.

PMID- 24293148
TI  - The effects of platelet-rich clot releasate on the expression of MMP-1 and type I
      collagen in human adult dermal fibroblasts: PRP is a stronger MMP-1 stimulator.
AB  - Platelet-rich plasma is widely used in acute and chronic ulcers due to its
      capacity to enhance the wound healing process. Fibroblasts are believed to be the
      most important cells in the production and remodeling of the extracellular matrix
      (ECM). Matrix metalloproteinase (MMP)-1 is the proteolytic enzyme of collagen I,
      and has a key role in collagen remodeling during wound healing. Whether or not
      platelet-rich clot releasate (PRCR) is able to effectively modulate the ECM, and
      the effect of PRCR on the expression of type I collagen and MMP-1 in human dermal
      fibroblasts was evaluated. Specifically, human adult dermal fibroblasts were
      incubated in PRCR-containing solutions for 24 and 48 h, after which the levels of
      collagen and MMP-1 were quantified by reverse transcription PCR at the
      transcriptional level, and ELISA and immunoblot analyses at the post
      transcriptional level. PRCR markedly up-regulated the expression of MMP-1 and
      type I collagen in fibroblasts incubated in 20 % PRCR solutions for 48 h. These
      findings suggest that increased MMP-1 expression after PRCR treatment enable
      remodeling the ECM.

PMID- 24293149
TI  - Influence of estrogen and variations at the BRCA1 promoter region on
      transcription and translation.
AB  - We analyzed wild-type (WT) and four sequence variants of the BRCA1 promoter
      region-found in patients selected for hereditary breast and ovarian cancer
      syndrome-in respect to their influence on transcription and translation
      efficiencies in transient transfection assays in the presence or absence of
      estrogen. Five types of plasmids containing the EGFP reporter gene proceeded by
      WT 5'UTR-a, WT 5'UTR-b, and the three 5'UTR-b variants were constructed to
      evaluate their influence on translation. Plasmids containing the firefly
      luciferase reporter gene were constructed with the WT BRCA1 promoter region
      (containing promoter alpha, 5'UTR-a, promoter beta, and 5'UTR-b) and with the
      four promoter variants for evaluating their influence on transcription and
      translation. All constructs were transfected in MCF7 cells maintained with and
      without estrogen. Expression of EGFP plasmids with WT 5'UTR-a was six to
      sevenfold higher than of plasmids with WT 5'UTR-b, expression of WT and the three
      variant 5'UTR-b plasmids showed slight differences in EGFP expression, and the
      presence or absence of estrogen result in non-significant changes in expression.
      Promoter's constructs that carry the variants WT or g.3988C showed a higher
      firefly luciferase activity when estrogen is present; conversely, no significant
      differences were found in the transcription efficiency of the reporter gene
      indicating that estrogen affect the translation rather than transcription. The
      presence or absence of estrogen did not affect the activity of firefly luciferase
      for constructs with the other promoter variants, being the transcription
      efficiencies equivalent in both conditions.

PMID- 24293150
TI  - Transcriptome characterization and sequencing-based identification of drought
      responsive genes in potato.
AB  - Potato (Solanum tubersosum L.) is relatively vulnerable to abiotic stress
      conditions such as drought, but the tolerance mechanisms to such stress in potato
      are largely unknown. To gain insight into the transcriptome dynamics that are
      associated with drought stress, genome-wide gene expression profile was conducted
      by Solexa sequencing to generate a large dataset and a comprehensive
      transcriptome profile for potato. Here, we report a reference for the potato
      transcriptome using leaf tissues under drought-stressed condition from a local
      potato cultivar 'Longshu 3'. Analysis of 86,965,482 RNA-Seq reads permitted the
      detection and quantification of expression levels of 7,284 genes at
      transcriptional levels, among them, 6,754 genes were enriched in draught-treated
      leaves while 6,419 in control. We identified 842 drought-responsive up-regulated
      and 494 down-regulated candidate genes with significantly differentially
      expression under continued drought stress treatments. Those differently expressed
      genes were mostly enriched in 89 gene categories and 21 KEGG pathways. Drought
      stressed leaves had increased expression of genes involved in stress response
      compared with control leaves. A subset of differentially expressed genes
      associated with drought response was examined using quantitative real-time PCR.
      These results provide a broad spectrum of candidate genes that are essential for
      understanding the molecular regulation of potato in response to abiotic stresses.

PMID- 24293151
TI  - In vivo effect of selected medicinal plants against gastrointestinal nematodes of
      sheep.
AB  - Nematode resistance to anthelmintic drugs affects small ruminant production
      globally. This study evaluated in vivo effects of five plant extracts as
      alternative nematode treatments. Animals were divided into six groups. Each group
      was randomly assigned a treatment: Abamectin and Praziquantel (CAP) (positive
      Control), ethanol extracts of Ananas comosus (AC), Aloe ferox (AF), Allium
      sativum (AS), Lespedeza cuneata (LC) and Warburgia salutaris (WS). These were
      applied as an oral dose (100 mg kg(-1) BW), one dose per week per sheep for 42
      days (Phase 1). From day 42 sheep were orally dosed for 3 consecutive days with
      the same treatments in the same groups (Phase 2). Rectal faecal samples were
      taken every 7 days up to day 63. Eggs per gram of faeces were counted in
      individual rectal samples, L3 larval stage was counted in faecal cultures, with
      four replicates per group. For plant extracts, EPG decreased (P < 0.001) with
      time and efficacy of plant increased (P < 0.001) with time. Ananas comosus and L.
      cuneata treatments had the highest efficacies of 58% and 61%, respectively, in
      Phase 1; and 77% and 81%, respectively, in Phase 2. Continuous treatment with
      these plants could further reduce nematode parasites and improve host health.

PMID- 24293152
TI  - Current reports on autoerotic deaths--five persistent myths.
AB  - Autoerotic deaths are defined as accidental deaths that occur during individual,
      solitary sexual activity in which some type of apparatus that was used to enhance
      the sexual stimulation of the deceased caused unintentional death. In the Western
      countries, the incidence of these deaths is of approximately 0.5 deaths per
      million inhabitants per year. In this paper, five myths about autoerotic death
      are explored. Myth #1: the manner of death in autoerotic death is usually
      accidental but could also be suicidal or natural (reality: by definition, all
      autoerotic deaths are accidental). Myth #2: autoerotic death can happen with a
      sexual partner (reality: by definition, autoerotic deaths are solitary
      activities). Myth #3: an escape mechanism must be found at the scene (reality:
      there is no escape mechanism to be observed at the scene in the majority of
      autoerotic deaths). Myth #4: all autoerotic deaths are related to asphyxia
      (reality: not all autoerotic deaths are related to asphyxia). Myth #5:
      masturbation is an important component of all autoerotic activities and therefore
      all autoerotic deaths (reality: evidence of masturbation at the scene is a rare
      finding). 

PMID- 24293153
TI  - Adenovirus and Norovirus Contaminants in Commercially Distributed Shellfish.
AB  - Shellfish complying with European Regulations based on quantification of fecal
      bacterial indicators (FIB) are introduced into markets; however, information on
      viruses, more stable than FIB, is not available in the literature. To assess the
      presence of noroviruses (NoVs) GI and GII and human adenoviruses (HAdV) in
      domestic and imported mussels and clams (n = 151) their presence was analyzed
      during winter seasons (2004-2008) in north-west Spanish markets through a routine
      surveillance system. All samples tested negative for NoV GI and 13 % were
      positive for NoV GII. The role of HAdV as viral indicator was evaluated in 20
      negative and 10 positive NoV GII samples showing an estimated sensitivity and
      specificity of HAdV to predict the presence of NoV GII of 100 and 74 % (cut-off
      0.5). The levels of HAdV and NoVs and the efficiency of decontamination in
      shellfish depuration plants (SDP) were evaluated analyzing pre- and post
      depurated mussels collected in May-June 2010 from three different SDP. There were
      no statistically significant differences in the prevalence and quantification of
      HAdV between pre- and post-depurated shellfish and between seawater entering and
      leaving the depuration systems. Moreover, infectious HAdV were detected in
      depurated mussels. These results confirm previous studies showing that current
      controls and depuration treatments limiting the number of FIB do not guarantee
      the absence of viruses in shellfish. 

PMID- 24293154
TI  - Model-based prediction of fusimotor activity and its effect on muscle spindle
      activity during voluntary wrist movements.
AB  - Muscle spindles provide critical information about movement position and
      velocity. They have been shown to act as stretch receptors in passive muscle,
      however, during active movements their behavior is less clear. In particular,
      spindle responses have been shown to be out-of-phase or phase advanced with
      respect to their expected muscle length-sensitivity. Whether this apparent
      discrepancy of spindle responses between passive and active movements is due to
      fusimotor (gamma-drive) remains unresolved, since the activity of fusimotor
      neurons during voluntary non-locomotor movements are largely unknown. We
      developed a computational model to predict fusimotor activity and to investigate
      whether fusimotor activity could explain the empirically observed phase advance
      of spindle responses. The model links a biomechanical wrist model to length- and
      gamma-drive-dependent transfer functions of type Ia and type II muscle spindle
      activity. Our simulations of two wrist-movement tasks suggest that (i)
      experimentally observed type Ia and type II activity profiles can to a large part
      be explained by appropriate, i.e. strongly modulated and task-dependent, gamma
      drive. That (ii) the empirically observed phase advance of type Ia or of type II
      profiles during active movement can be similarly explained by appropriate gamma
      drive. In summary, the simulation predicts that a highly task-modulated
      activation of the gamma-system is instrumental in producing a large part of the
      empirically observed muscle spindle activity for voluntary wrist movements. 

PMID- 24293155
TI  - Insight of endo-1,4-xylanase II from Trichoderma reesei: conserved water-mediated
      H-bond and ion pairs interactions.
AB  - Endo-1,4-Xylanase II is an enzyme which degrades the linear polysaccharide beta
      1,4-xylan into xylose. This enzyme shows highest enzyme activity around 55 
      degrees C, even without being stabilized by the disulphide bridges. A set of nine
      high resolution crystal structures of Xylanase II (1.11-1.80 A) from Trichoderma
      reesei were selected and analyzed in order to identify the invariant water
      molecules, ion pairs and water-mediated ionic interactions. The crystal structure
      (PDB-id: 2DFB) solved at highest resolution (1.11 A) was chosen as the reference
      and the remaining structures were treated as mobile molecules. These structures
      were then superimposed with the reference molecule to observe the invariant water
      molecules using 3-dimensional structural superposition server. A total of 37
      water molecules were identified to be invariant molecules in all the crystal
      structures, of which 26 invariant molecules have hydrogen bond interactions with
      the back bone of residues and 21 invariant water molecules have interactions with
      side chain residues. The structural and functional roles of these water molecules
      and ion pairs have been discussed. The results show that the invariant water
      molecules and ion pairs may be involved in maintaining the structural
      architecture, dynamics and function of the Endo-1,4-Xylanase II. 

PMID- 24293156
TI  - Structure-function studies on non-synonymous SNPs of chemokine receptor gene
      implicated in cardiovascular disease: a computational approach.
AB  - Among non-communicable diseases, cardiovascular disease (CVD) is claimed to be
      the leading cause of death worldwide. The chemokine (C-C Motif) receptor 5 (CCR5)
      gene has a strong association with the development of CVD and may culminate in
      myocardial infarction. In this study, its potential variations have been
      determined using molecular dynamics approach. Single nucleotide polymorphisms
      (SNPs) are the predominant mutations and their deleterious effects were initially
      screened using prediction tools. Further, for the 75 % of deleterious non
      synonymous SNPs predicted in common by the above tools, root mean square
      deviation (RMSD) and stability residues were determined using SWISS-PDB viewer
      and SRide server respectively. Accordingly, four point mutations L55Q, V131F,
      R223W, and G301R which had RMSD >=2.0 A were selected and trajectory analyses
      were performed. In common, all trajectory analyses reported no similarities
      between native and mutants. Combined mutational analysis comparing all the
      mutants together with the native also showed significant and similar changes.
      Thus we conclude that the above four mutations are the potential targets of CCR5
      and may lead to CVD. 

PMID- 24293157
TI  - Junctional spitz tumor (nevus) of the upper lip.
AB  - Spitz tumor (nevus) is a rare, melanocytic lesion that primarily affects children
      and adolescents. The lesion may share many clinical and histological similarities
      with malignant melanoma and careful microscopic examination is required to render
      the proper diagnosis. Complete excision with close follow-up is considered the
      appropriate treatment. Despite the common presentation of Spitz nevi on the
      facial skin, lip involvement has only rarely been described in the English
      language literature. In the present study, a case of Spitz tumor located on the
      vermilion border of the upper lip in a 16-year old female patient is reported. 

PMID- 24293158
TI  - LINE-1 hypomethylation in spermatozoa is associated with Bisphenol A exposure.
AB  - Bisphenol A (BPA) is an endocrine disruptor with potentially harmful effects on
      humans. However, epigenetic mechanisms that modulate the effects of BPA remain
      unclear. Methylation of long interspersed nucleotide elements (LINE-1) is a
      marker of genome-wide methylation status. This study aims to examine whether BPA
      exposure was associated with LINE-1 methylation changes in men. Male factory
      workers in Hunan, China (N = 149) were studied, 77 with BPA exposure in workplace
      (BPA-exposed group) and 72 without BPA exposure in workplace (control group). Pre
      shift and post-shift urine samples were collected from the BPA-exposed group and
      spot urine samples were collected from the control group. Urine samples were
      assessed for BPA. In addition, blood and semen samples were collected from both
      groups for LINE-1 methylation analysis. In multivariate analysis adjusted for
      age, education, smoking habits and alcohol consumption, sperm LINE-1 methylation
      level was significantly lower in BPA exposed workers (p < 0.001) compared to that
      in the unexposed workers. Linear regression analysis also showed that log
      transformed urine BPA levels were inversely associated with sperm LINE-1
      methylation (p < 0.0001), but not peripheral blood cell LINE-1 methylation.
      Moreover, the association between urine BPA level and semen quality was not
      attenuated after adjustments for LINE-1 level. In summary, the observed
      independent relationship between BPA exposure and LINE-1 methylation may have
      public health implications on reproductive health in men because of ubiquitous
      exposure to BPA. 

PMID- 24293160
TI  - Preliminary Findings of Single- and Multifocused Epileptiform Discharges in
      Nonepileptic Psychiatric Patients.
AB  - Epileptiform discharges (EDs) in nonepileptic populations remain controversial as
      to their role in psychopathology. Previous studies have unsuccessfully attempted
      to correlate specific waveforms of EDs, defined by duration and morphology, with
      broad diagnostic categories such as depression and anxiety. These diagnostic
      categories often include heterogeneous patient populations, with potentially
      divergent biological underpinnings of clinical presentation. This study examined
      epileptiform activities as a single phenomenon, identifying the relationships
      between distribution patterns of EDs and endorsement of clinical symptoms across
      affective, cognitive, and somatic domains. In a sample of 71 nonepileptic
      psychiatric patients, those with EDs appearing in homologous electrode pairs
      endorsed significantly fewer symptoms related to affective deregulation. These
      patients were also significantly less likely to endorse a history of severe
      symptomatology, including suicidal ideation/previous attempt, self-injurious
      behavior, psychoses or dissociation, and previous psychiatric hospitalization.
      Conversely, patients with isolated EDs focused to a single brain region endorsed
      greater affective deregulation and severe clinical symptoms. These findings offer
      new possibilities regarding the potentially protective role that EDs may play
      when distributed across hemispheres, particularly in light of recent theories
      exploring functional connectivity of neuronal networks.

PMID- 24293159
TI  - Diffusion tensor image registration using hybrid connectivity and tensor
      features.
AB  - Most existing diffusion tensor imaging (DTI) registration methods estimate
      structural correspondences based on voxelwise matching of tensors. The rich
      connectivity information that is given by DTI, however, is often neglected. In
      this article, we propose to integrate complementary information given by
      connectivity features and tensor features for improved registration accuracy. To
      utilize connectivity information, we place multiple anchors representing
      different brain anatomies in the image space, and define the connectivity
      features for each voxel as the geodesic distances from all anchors to the voxel
      under consideration. The geodesic distance, which is computed in relation to the
      tensor field, encapsulates information of brain connectivity. We also extract
      tensor features for every voxel to reflect the local statistics of tensors in its
      neighborhood. We then combine both connectivity features and tensor features for
      registration of tensor images. From the images, landmarks are selected
      automatically and their correspondences are determined based on their
      connectivity and tensor feature vectors. The deformation field that deforms one
      tensor image to the other is iteratively estimated and optimized according to the
      landmarks and their associated correspondences. Experimental results show that,
      by using connectivity features and tensor features simultaneously, registration
      accuracy is increased substantially compared with the cases using either type of
      features alone.

PMID- 24293161
TI  - Real-time functional mapping with electrocorticography in pediatric epilepsy:
      comparison with fMRI and ESM findings.
AB  - SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection)
      software provides real-time functional mapping (RTFM) of eloquent cortex for
      epilepsy patients preparing to undergo resective surgery. This study presents the
      first application of paradigms used in functional magnetic resonance (fMRI) and
      electrical cortical stimulation mapping (ESM) studies for shared functional
      cortical mapping in the context of RTFM. Results from the 3 modalities are
      compared. A left-handed 13-year-old male with intractable epilepsy participated
      in functional mapping for localization of eloquent language cortex with fMRI,
      ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex.
      Several paradigms were sequentially presented: passive (listening to stories) and
      active (picture naming and verb generation). For verb generation and story
      processing, fMRI showed atypical right lateralizing language activation within
      temporal lobe regions of interest and bilateral frontal activation with slight
      right lateralization. Left hemisphere ESM demonstrated no eloquent language
      areas. RTFM procedures using story processing and picture naming elicited
      activity in the right lateral and basal temporal regions. Verb generation
      elicited strong right lateral temporal lobe activation, as well as left frontal
      lobe activation. RTFM results confirmed atypical language lateralization evident
      from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM
      stimulation paradigm during presurgical evaluation. Block design paradigms used
      in fMRI may be optimal for this purpose. Further development is needed to create
      age-appropriate RTFM test batteries.

PMID- 24293162
TI  - The Clinical Features and Prognosis of Patients With Nonconvulsive Status
      Epilepticus in the Neurological Intensive Care Unit of a Tertiary Referral Center
      in Turkey.
AB  - The availability of video electroencephalography monitoring (VEEGM) in
      neurological intensive care units has allowed the recognition and treatment of
      nonconvulsive status epilepticus (NCSE). However, little is known about
      characteristics, management, and outcomes in patients with NCSE in developing
      countries. We retrospectively reviewed the video-EEG reports of 120 patients who
      were monitored from November 2009 to March 2013. Indications for video-EEG were
      mostly unexplained alterations of consciousness or witnessed convulsive seizures.
      We identified the clinical characteristics, treatment regimes, and outcomes of
      patients with NCSE and tried to determine which parameters were associated with
      prognosis. NCSE was detected in 12/120 (10%) patients (3 females, 9 males; age 24
      86 years). Admission diagnoses were: stroke (3), epilepsy (3), autoimmune limbic
      encephalitis (3), herpes encephalitis (1), presumed encephalitis-cardiac arrest
      (1), and malignancy (1). Eight patients had witnessed convulsive seizures before
      video-EEG. Interictal periodic epileptiform discharges were detected in 9
      patients. In one-third of patients, >=2 EEG recordings were required to capture
      seizures. In addition to anticonvulsants, 3 patients received immunosuppressive
      therapy, while intravenous anesthetics were given to 7 patients. Four patients
      (33.3%; 1 female, 3 males; age 51-67 years; etiology: stroke, autoimmune
      encephalitis, encephalitis-cardiac arrest, and malignancy; Glasgow coma scale
      (GCS) score <8 in 3 patients; all had periodic discharges; intravenous
      anesthetics were used) died in the intensive care unit. NCSE is not an infrequent
      finding in neurological intensive care units, thus necessitating prolonged video
      EEG monitoring in patients at risk. Witnessed convulsions may indicate the
      presence of nonconvulsive seizures in patients with altered consciousness.
      Repeated recordings may increase the detection of ictal events. Periodic
      epileptiform discharges are commonly observed and may predict poor prognosis.
      Mortality seems to be influenced mostly by the underlying etiology.

PMID- 24293163
TI  - Gastric bypass surgery may improve beta cell apoptosis with ghrelin
      overexpression in patients with BMI >= 32.5 kg/m(2.).
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery can lead to long-term
      remission of type 2 diabetes mellitus, depending on changes in weight and
      circulating levels of gut hormones. The general objectives of this study were to
      evaluate changes in plasma levels of the ghrelin gene products following RYGB
      surgery and to determine the role of ghrelin in inhibiting apoptosis of INS-1
      cells induced by hyperglycemia. METHODS: Sixteen obese Chinese patients with type
      2 diabetes mellitus who underwent gastric bypass surgery were assessed in this
      investigation. Blood plasma levels of acylated ghrelin (AG), unacylated ghrelin
      (UAG), and obestatin (OB) were measured both before and 12 months after RYGB
      surgery. To determine the effect of ghrelin on inhibition of apoptosis, INS-1
      cells were cultured in a high glucose concentration and treated with AG, UAG, or
      OB. Cell viability was assessed using the MTT assay, and apoptosis was evaluated
      by flow cytometry with Annexin-V FITC/PI double staining and transmission
      electron microscopy. Intracellular calcium trafficking was assessed using flow
      cytometry and confocal microscopy. All the data was processed using the SPSS
      statistical package and expressed as means +/- SD, with p < 0.05 considered
      statistically significant. RESULTS: Fasting and postprandial plasma levels of AG,
      UAG, and OB were significantly elevated 1 year after RYGB surgery. Mean fasting
      plasma AG, UAG, and OB increased from preoperative levels of 37.0, 462, and 69.4
      pg/mL, respectively, to 61.4, 804, and 112 pg/mL (with p < 0.05) 1 year after
      surgery. Mean 120-min postprandial plasma AG, UAG, and OB increased from
      preoperative levels of 23.8, 287, and 53.8 pg/mL, respectively, to 39.7, 516, and
      69.0 pg/mL (with p < 0.05) postoperatively. After a 1-week culture of INS-1 beta
      cell in high glucose, peptide treatment showed increased cell survival by 69 %
      (AG), 60 % (UAG), and 73 % (OB) and decreased apoptosis by 49 % (AG), 37 % (UAG),
      and 38 % (OB) compared to cells cultured in high glucose without peptides,
      respectively (with p < 0.05). Treatment with AG, UAG, and OB inhibited
      intracellular calcium mobilization and intramitochondrial calcium accumulation in
      INS-1 cells to protect the cells from hyperglycemia-induced apoptosis.
      CONCLUSIONS: The remission of diabetes following RYGB surgery seems to be
      associated with increased plasma levels of AG, UAG, and OB. Moreover, the ghrelin
      gene products probably protect beta cells by maintaining calcium homeostasis.
      Additional mechanisms, currently unclear, are likely to be involved as well.

PMID- 24293164
TI  - Invariant chain as a vehicle to load antigenic peptides on human MHC class I for
      cytotoxic T-cell activation.
AB  - Protective T-cell responses depend on efficient presentation of antigen (Ag) in
      the context of major histocompatibility complex class I (MHCI) and class II
      (MHCII) molecules. Invariant chain (Ii) serves as a chaperone for MHCII molecules
      and mediates trafficking to the endosomal pathway. The genetic exchange of the
      class II-associated Ii peptide (CLIP) with antigenic peptides has proven
      efficient for loading of MHCII and activation of specific CD4(+) T cells. Here,
      we investigated if Ii could similarly activate human CD8(+) T cells when used as
      a vehicle for cytotoxic T-cell (CTL) epitopes. The results show that wild type
      Ii, and Ii in which CLIP was replaced by known CTL epitopes from the cancer
      targets MART-1 or CD20, coprecipitated with HLA-A*02:01 and mediated
      colocalization in the endosomal pathway. Furthermore, HLA-A*02:01-positive cells
      expressing CLIP-replaced Ii efficiently activated Ag-specific CD8(+) T cells in a
      TAP- and proteasome-independent manner. Finally, dendritic cells transfected with
      mRNA encoding IiMART-1 or IiCD20 primed naive CD8(+) T cells. The results show
      that Ii carrying antigenic peptides in the CLIP region can promote efficient
      presentation of the epitopes to CTLs independently of the classical MHCI peptide
      loading machinery, facilitating novel vaccination strategies against cancer. 

PMID- 24293165
TI  - Short-term amiodarone therapy after reversion of persistent atrial fibrillation
      reduces recurrences at 18 months.
AB  - BACKGROUND: The aim of this study was to compare the outcome of 3 months vs. 18
      months of amiodarone treatment after atrial fibrillation (AF) conversion in
      patients who experienced the first episode of persistent AF. METHODS: We included
      51 patients who experienced the first episode of persistent AF receiving
      amiodarone (600 mg) daily for 4-6 weeks. If AF persisted, electrical
      cardioversion (ECV) was performed. All patients received amiodarone (200 mg
      daily) for 3 months and then were randomized to amiodarone (Group I) or placebo
      (Group II) and followed for 15 months. The control group comprised 9 untreated
      patients undergoing ECV. Treatment effectiveness was evaluated using a Bayesian
      model. RESULTS: Eighteen months after AF reversion, 22 (81.5%) patients in Group
      I, 13 (54.2%) patients in Group II, and 1 (11.1%) patient in the control group
      remained in sinus rhythm. No differences were found between Group I patients who
      required ECV and Group II patients. Sinus rhythm was preserved in all Group I
      patients when it was achieved during amiodarone administration. Limiting adverse
      effects occurred in 3 (11.1%) patients in Group I. CONCLUSIONS: In patients
      regaining sinus rhythm after the first episode of persistent AF, a 3-month
      amiodarone treatment after reversion is a reasonable option for rhythm control.

PMID- 24293166
TI  - Biomarkers of myocardial injury with different energy sources for atrial
      fibrillation catheter ablation.
AB  - BACKGROUND: Our study aims to compare acute myocardial injury biomarker rise
      after atrial fibrillation ablation performed with different technologies. METHODS
      AND RESULTS: One hundred and ten patients were treated with pulmonary vein
      isolation with 4 different technologies: open-irrigated tip radiofrequency (RF)
      catheter in35 patients (Group A), cryoballoon in 35 patients (Group B), visually
      guided laser balloon in 20 patients (Group C), open-irrigated tip RF catheter
      with contact-force-sensing technology in 20 patients (Group D). Post-procedure
      samples of cardiac troponin I (cTnI) and creatinine kinase-MB (CK-MB) were
      collected at 19 +/- 3 h and 43 +/- 3 h after ablation. At the first
      postprocedural sample, cTnI and CK-MB levels were found elevated in all 110
      patients with a median value of 2.11 ng/mL and 8.95 ng/mL, respectively. Group B
      showed cTnI levels increased (median 5.96 ng/mL) compared to other groups (median
      Group A: 1.72 ng/mL, Group C: 1.54 ng/mL, Group D: 2.0 ng/mL; p < 0.001). Also CK
      MB levels resulted higher in cryoablation (median 26.4 ng/mL) compared to other
      groups (median Group A: 6.40 ng/mL, Group C: 7.15 ng/mL, Group D: 6.50 ng/mL; p <
      0.001). No significant association was observed between biomarker levels and
      recurrences of atrial fibrillation after a mean follow-up of 369 +/- 196 days.
      CONCLUSIONS: Highest markers for myocardial injury were observed in the
      cryoballoon group. It is possible that a longer delivery energy duration and
      other factors affecting lesion size resulted in higher amount of cardiac injury
      in cryoablation. The higher levels of cardiac biomarkers did not translate into a
      better outcome and its physiologic significance is unknown.

PMID- 24293167
TI  - Effect of oral vitamin C on atrial fibrillation development after isolated
      coronary artery bypass grafting surgery: A prospective randomized clinical trial.
AB  - BACKGROUND: Some evidences have shown the role of antioxidant vitamins in
      preventing atrial fibrillation (AF) after coronary artery bypass grafting (CABG)
      surgery. We sought to determine the effect of oral vitamin C on the incidence of
      postoperative AF in patients undergoing elective isolated on-pump CABG surgery.
      METHODS: One-hundred patients who underwent isolated CABG surgery were
      prospectively assigned into two groups: Group 1 - 50 patients received 2 g of
      oral vitamin C before and 500 mg twice daily lasting for 5 days after surgery;
      Group 2 - 50 patients as the control group did not receive any. All patients were
      continuously monitored after surgery in the intensive careunit (ICU), and then
      Holter monitoring was implemented for 72 h. RESULTS: The mean of patients' age
      was 61.31 +/- 6.42 years. Postoperative AF occurred in 16 and 4 patients in
      control and treatment groups, respectively (32% vs. 8%, p = 0.003). The ICU stay
      was 1.79 +/- 0.313 and 2.10 +/- 0.61 days for vitamin C and control groups,
      respectively (p = 0.002). The hospital stay was significantly lower in vitamin C
      group compared with that of the control group (5.32 +/- 0.59 vs. 5.74 +/- 1.30
      days, respectively, p = 0.041). Baseline erythrocyte sedimentation rate (OR
      1.030, 95% CI 1.003-1.058, p = 0.030) and taking vitamin C (OR 8.068, 95% CI
      1.783-36.517, p = 0.007) were the independent predictors of postoperative AF.
      CONCLUSIONS: Oral vitamin C can be safely used to decrease the incidence of
      postoperative AF in patients undergoing elective isolated on-pump CABG surgery.

PMID- 24293168
TI  - Oncogenic Papillomavirus and Polyomavirus in Water Environments: Is There a
      Potential for Waterborne Transmission?
AB  - Waterborne exposure to human viruses through contact with sewage-contaminated
      water environments can result in infections associated with a wide range of
      illnesses. Gastrointestinal symptoms are the most commonly encountered
      manifestations of waterborne viral illness. Respiratory diseases, neurological
      diseases and paralysis can also occur. Whether viral infections resulting in
      health outcomes like cancer might also be transmitted by the waterborne route is
      unknown. Recently, viruses belonging to two oncogenic groups-Human
      Papillomaviruses (HPVs) and Human Polyomaviruses (HPyVs)-have been detected in
      urban sewages worldwide. The latter have also been identified in other water
      environments. HPVs are epitheliotropic viruses responsible for several diseases
      of skin and mucosae, from common warts to squamous intraepithelial lesions that
      can either heal or progress to invasive carcinoma of the cervix, vulva, vagina,
      penis, anus or oropharynx. Human PyVs infect different tissues and organs,
      causing infections that are usually subclinical in immunocompetent individuals
      but can be serious in immunocompromised hosts. These pathogens belong to a family
      of DNA tumour viruses. Merkel cell polyomavirus, a HPyV identified in recent
      years, has attracted much attention due to its link with a rare and aggressive
      form of human cancer. Merkel cell carcinoma, the incidence of which has tripled
      over the past two decades. JC polyomavirus and BK polyomavirus are also
      potentially oncogenic. The observed abundance and wide dissemination of HPVs and
      HPyVs in water environments strongly suggest the need to shed light on the fate
      of these viruses in water environments and to elucidate their potential for
      waterborne transmission. Such information is essential for the improvement of
      wastewater management programs in terms of both sewage treatment and water
      quality surveillance. 

PMID- 24293169
TI  - Specific detection of Bjerkandera adusta by polymerase chain reaction and its
      incidence in fungus-associated chronic cough.
AB  - Chronic cough is a common symptom at outpatient care. An uncontrollable cough
      with difficulty in treatment is called chronic idiopathic cough. Recent reports
      have demonstrated that the presence of basidiomycetous fungi in sputum is an
      important clinical finding that assists in clarifying the cause of chronic cough
      in some cases. Research has suggested that Bjerkandera adusta is related to
      fungus-associated chronic cough (FACC). FACC is defined as a chronic cough
      associated with basidiomycetous fungi found in induced sputum and can be treated
      with antifungal medication. B. adusta is one of the basidiomycetous fungi that
      exist in cosmopolitan environments. The aim of this study was to develop a B.
      adusta detection method using polymerase chain reaction (PCR) with a specific
      primer set and to research the incidence of B. adusta in FACC. The new method
      successfully detected B. adusta from FACC patients. The incidence of B. adusta in
      FACC was 42.86 %. Antifungal drugs were effective in most cases. Significant
      differences in treatment duration between B. adusta patients and non-B. adusta
      patients were observed. It is therefore suggested that the presence of B. adusta
      may be one of the allergic intractable factors of chronic cough. This finding may
      provide identifiable differences in clinical manifestations between B. adusta and
      non-B. adusta in FACC and lead to possible differing remedies to treat the two
      forms. PCR can specifically detect B. adusta from patients suffering from chronic
      cough and provides a new diagnosis for FACC associated with B. adusta. 

PMID- 24293170
TI  - Cryptococcal meningitis in Senegal: epidemiology, laboratory findings,
      therapeutic and outcome of cases diagnosed from 2004 to 2011.
AB  - BACKGROUND: Cryptococcal meningitis is one of the most important opportunistic
      infection and a major contributor to early mortality. In sub-Saharan Africa,
      particularly in Senegal, prevalence of cryptococcal meningitis remains high. This
      study aimed to describe the epidemiology, laboratory profile, therapeutic and
      outcome of cases diagnosed in Dakar. METHODS: We analyzed the cryptococcosis
      cases diagnosed at the department of parasitology-mycology in Fann Teaching
      Hospital in Dakar from 2004 to 2011. The diagnosis was confirmed by culture on
      Sabouraud's dextrose agar and/or by India ink preparation and/or by cryptococcal
      antigen detection. The diagnosis methods were assessed by using culture as
      reference. RESULTS: A total of 106 cases of cryptococcal meningitis were
      diagnosed. The prevalence of cryptococcal meningitis was 7.8 %. The mean age of
      the patients was 40.17 +/- 9.89 years. There were slightly more male (53.8 %)
      than female (46.2 %) patients; 89.6 % were found to be infected with HIV, and the
      median CD4+ count was 27/mm(3). Approximately 79.5 % of the patients had <100
      CD4+ lymphocytes/mm(3). India ink staining presented sensitivity at 94.11 % and
      specificity at 100 %. Sensitivity and specificity of cryptococcal antigen
      detection in cerebrospinal fluid were, respectively, 96.96 and 15.78 %. The most
      frequently used antifungal drug was fluconazole (86.7 %), and the mortality rate
      was 62.2 % (66 deaths). CONCLUSION: Early diagnosis is essential to control
      cryptococcosis, and countries should prioritize widespread and reliable access to
      rapid diagnostic cryptococcus antigen assays. But it is important to make
      available conventional methods (India ink and culture) in the maximum of
      laboratory in regional health facilities.

PMID- 24293171
TI  - A quantitative assessment of the insertional footprints of the hip joint capsular
      ligaments and their spanning fibers for reconstruction.
AB  - Quantitative descriptions of the hip joint capsular ligament insertional
      footprints have been reported. Using a three-dimensional digitizing system, and
      computer modeling, the area, and dimensions of the three main hip capsular
      ligaments and their insertional footprints were quantified in eight cadaveric
      hips. The iliofemoral ligament (ILFL) attaches proximally to the anterolateral
      supra-acetabular region (mean area = 4.2 cm(2)). The mean areas of the ILFL
      lateral and medial arm insertional footprints are 4.8 and 3.1 cm(2),
      respectively. The pubofemoral ligament (proximal footprint mean area = 1.4 cm(2))
      blends with the medial ILFL anteriorly and the proximal ischiofemoral ligament
      (ISFL) distally without a distal bony insertion. The proximal and distal ISFL
      footprint mean areas are 6.4 and 1.2 cm(2), respectively. The hip joint capsular
      ligaments have consistent anatomic and insertional patterns. Quantification of
      the ligaments and their attachment sites may aid in improving anatomic repairs
      and reconstructions of the hip joint capsule using open and/or arthroscopic
      techniques.

PMID- 24293173
TI  - Atrial fibrillation following open heart surgery: long-term incidence and
      prognosis.
AB  - INTRODUCTION: While early postoperative atrial fibrillation (post op AF)
      following valve and coronary artery bypass surgery is a known common cause of
      increased morbidity and mortality, the late recurrence of AF long term in this
      group of patients has not been well studied. OBJECTIVE: The objective of this
      study was to assess the late recurrence and predictors of AF in patients
      undergoing open heart surgery. METHODS: From a prospective cardiovascular surgery
      registry, 519 patients with no prior history of AF who underwent open heart
      surgery for cardiac bypass/valvular surgeries between May 2000 and April 2004
      were followed until May 2009. A Cox proportional hazards model was used to assess
      the impact of early post op AF on the long-term AF after adjusting for
      significant covariates RESULTS: Of these patients, 25.6 % (133) had early (0-3
      months) post op AF (group A). The remainder of patients were considered as
      controls (group B, n = 386). Late occurrence of AF (3-84 months) was 5.3 % (n =
      28) after a mean follow up duration of 5 +/- 1.9 years. The late occurrence of AF
      in group A (recurrent AF) was significantly higher than in group B (11 vs 3 % n =
      15 vs 13, p = 0.0002). Early postoperative AF was a significant predictor of late
      recurrence of AF in multivariate analysis (hazard ratio (HR) 3.9, CI 1.8-8.4, p =
      0.0003). Group A also had higher mortality compared to group B (21 vs 13 %, n =
      28 vs n = 51, p = 0.003) with early postoperative AF showing a trend towards
      higher mortality on multivariate analysis (HR 1.7, p = 0.06). CONCLUSIONS: Late
      recurrence of AF is higher than was previously thought to be in patients
      experiencing early post operative AF with a trend towards higher long-term
      mortality. Post op AF should not be dismissed as a benign entity and these
      patients should be followed closely.

PMID- 24293174
TI  - Cryoablation versus radiofrequency ablation of atrioventricular nodal reentrant
      tachycardia.
AB  - BACKGROUND: Ablation of the slow pathway is an established cure for
      atrioventricular nodal reentrant tachycardia (AVNRT). Periprocedural damage to
      the conduction system is a major concern during AVNRT ablation, and cryoablation
      (CRYO) has been suggested to improve the procedural safety compared to standard
      radiofrequency (RF) ablation, without reducing the procedural success. OBJECTIVE:
      We performed a systematic review and meta-analysis of studies comparing CRYO with
      RF ablation of AVNRT. METHODS: We searched PubMed, CENTRAL, the BioMed Central,
      EMBASE, CardioSource, clinicaltrials.gov, and ISI Web of Science (January 1980 to
      July 2013). No language restriction was applied. Two independent reviewers
      screened titles and abstracts to identify studies that compared the procedural
      outcomes of AVNRT ablation with either CRYO or RF energy. Two independent
      reviewers assessed the risk of bias according to the Cochrane Collaboration, and
      extracted patient, study characteristics, and procedural outcome data. Results
      are expressed as odds ratio (OR) or as weighted mean difference (WMD) with their
      95 % confidence interval (CI). RESULTS: Fourteen studies (5 prospective
      randomized and 9 observational) with 2,340 patients (mean age range 13 to 53
      years, 1,522 (65 %) females) were included in the analysis. RF ablation was
      performed in 1,262 (54 %) patients, while CRYO in 1,078 (46 %) patients. Acute
      success (abolition of dual atrioventricular node physiology or single echo beats)
      was achieved in 88 % of patients treated with RF versus 83 % of those treated
      with CRYO (OR = 0.72, 95 % CI 0.46 to 1.13; P = 0.157). RF ablation was
      associated with shorter total procedure time (WMD = -13.7 min, 95 % CI -23 to 
      4.3 min; P = 0.004), but slightly longer fluoroscopy time (WMD = +4.6 min 95 % CI
      +1.7 to +7.6 min; P = 0.002). Permanent atrioventricular block occurred in 0.87 %
      RF cases and in no CRYO case (OR = 3.60, 95 % CI 1.09 to 11.81; P = 0.035). Over
      a median follow-up of 10.5 months (range 6 to 12 months), freedom from recurrent
      AVNRT was 96.5 % in the RF group versus 90.9 % in the CRYO group (OR = 0.40, 95 %
      CI 0.28 to 0.58; P < 0.001). At meta-regression analysis, no clinical or
      procedural variable had a significant interaction with the results above.
      CONCLUSIONS: In patients undergoing AVNRT ablation, RF significantly reduces the
      risk of long-term arrhythmia recurrence compared to CRYO, but is associated with
      a higher risk of permanent atrioventricular block.

PMID- 24293175
TI  - A novel fluoroscopic method of measuring right-to-left interlead distance as a
      predictor of reverse left ventricular remodeling after cardiac resynchronization
      therapy.
AB  - PURPOSE: In spite of technological breakthroughs, the choice of a suitable
      location for the coronary sinus (CS) lead in biventricular implants is still
      mostly empiric. The aim of this study was to investigate the utility of a
      radiological index-the distance between the right ventricular (RV) and CS lead
      tips on fluoroscopic recordings, measured by means of a new method-as a tool for
      selecting the most profitable left ventricular (LV) lead position. METHODS: Forty
      nine consecutive patients (36 male, 13female; mean age 63 +/- 19 year), in whom
      the LV electrode was implanted in a lateral/postero-lateral position in the CS,
      were evaluated immediately after implantation. The fluoroscopic distances between
      the RV and LV lead tips were calculated off-line in antero-posterior (2DAP) and
      latero-lateral (2DLL) projections by means of integrated software. RESULTS: On 1
      year follow-up evaluation, 53 % patients were classed as responders (R) (>15 %
      reduction in LV end-systolic volume) and 47 % as non-responders (NR). On receiver
      operating curve analysis, 2DAP and 2DLL showed cut-off values of 81 mm and 51 mm,
      respectively. In discriminating between R and NR, 2DAP >81 mm displayed 95 %
      specificity and 74 % sensitivity, while 2DLL >51 mm displayed 74 % specificity
      and 92 % sensitivity. On multivariate analysis, the cut-off values of 2DAP and
      2DLL were significantly predictive of R to CRT. CONCLUSIONS: In our single-center
      prospective experience, RV-LV interlead distance measured by means of a novel
      method on fluorographic recordings correlated with CRT response. The use of this
      method as an intra-operative guide to identifying suitable lead placement in the
      CS needs evaluating on-line and on a large scale.

PMID- 24293177
TI  - Evaluation of the safety and effectiveness of the CryoMedix cryoablation catheter
      system for the treatment of atrial flutter and fibrillation.
AB  - BACKGROUND: Catheter ablation of atrial flutter and fibrillation (AFL and AF) has
      typically been performed with radiofrequency energy. Cryoablation has recently
      been used for AF and AFL, but its success has been limited by the nadir
      temperature achievable using nitrous oxide as a refrigerant. In this study, a
      novel approach allowing for use of a liquid refrigerant capable of achieving
      lower nadir temperatures was tested in a canine model with cavo-tricuspid isthmus
      (CTI) and left atrial (LA) ablation. METHODS AND RESULTS: In six dogs, under
      general anesthesia, standard catheters were placed in the coronary sinus and
      right ventricular apex, and the CryoMedix cryoablation catheter (CAC) in the
      right (CTI) and left atrium (for ablation, across the LA roof, mitral isthmus,
      and LA septum). Double-freezes up to 2 min each were performed, with a 30-s thaw
      cycle between freezes. Ablated areas were subsequently grossly inspected and
      photographed and tissues fixed in formalin for histologic analysis to determine
      if the lesions were contiguous and transmural. In all animals, long linear (from
      4-8 cm) transmural atrial lesions were observed on gross and histological
      examination in the left atrial roof, septum and mitral isthmus, and across the
      cavo-trisucpid isthmus. In all animals, bi-directional cavo-tricuspid isthmus
      block was observed after ablation, during pacing from the coronary sinus ostium
      and low lateral right atrium, respectively. Up to 50% thickness lesions were
      observed in the right ventricle below the tricuspid valve in all animals. There
      were no acute complications noted in any animals. CONCLUSIONS: The CAC system
      produces extremely negative freezing temperatures, significantly lower than those
      reported for nitrous oxide based systems. The CTI was easily ablated with the CAC
      system, producing bi-directional conduction block, suggesting a potential role
      for the system in the treatment of isthmus-dependent atrial flutter. Transmural
      LA lesions were also produced with the CAC system, suggesting a potential role in
      treating AF.

PMID- 24293176
TI  - The impact of age on clinical outcomes following cardiac resynchronisation
      therapy.
AB  - BACKGROUND: Cardiac resynchronisation therapy (CRT) is an established treatment
      for selected patients with symptomatic left ventricular (LV) systolic
      dysfunction. Heart failure (HF) is primarily a disease of the elderly; however,
      these patients are underrepresented in CRT trials. Our aim was to evaluate the
      impact of age on clinical outcomes following CRT. METHODS: A consecutive series
      of 177 patients was identified and divided into those aged <= 7 5 years (n = 131,
      mean +/- SD 62.1 +/- 11.2 years) and those aged >75 years (n = 46, mean +/- SD
      80.7 +/- 4.1 years). The primary end point was a composite of all-cause mortality
      or HF hospitalisation. RESULTS: During a median +/- IQR follow up of 28.5 +/-
      33.7 months, the event rate for the primary end point was significantly higher in
      the elderly compared to younger patients (20.1 vs. 11.1 %, respectively, logrank
      p = 0.020). This was mainly driven by an excess mortality rate among those aged
      >75 years (10 vs. 4.7%, respectively, logrank p = 0.018) whereas HF
      hospitalisation rates were similar between groups (10 vs. 6.4%, respectively,
      logrank p = 0.301). After adjusting for comorbidities and ICD status, the
      difference in the composite end point rates was attenuated and no longer
      significant (HR 1.580, 95% CI 0.899-2.778; p = 0.112 for >75 vs. <= 75 years).
      Notably, both groups demonstrated similar response rates to CRT in terms of
      symptomatic improvement, reverse LV remodelling and neurohormonal activation.
      CONCLUSIONS: CRT is equally effective in the elderly as in younger patients to
      reduce adverse clinical outcomes. For those who fulfil the prerequisite selection
      criteria, it should be considered as a valid therapeutic option.

PMID- 24293178
TI  - Single-center experience of a quadripolar pacing lead for cardiac
      resynchronization therapy.
AB  - AIM: Recent studies have shown that a quadripolar left ventricular (LV) lead can
      result in low rates of dislocation and phrenic nerve stimulation (PNS) acutely
      and on medium-term follow-up in cardiac resynchronization therapy (CRT). We
      evaluated the outcomes of CRT patients in whom a quadripolar LV lead was
      implanted in our institution. METHODS: We studied 45 consecutive heart failure
      patients (75 % men; age, 70.3 +/- 9.0 years) following successful implantation of
      a quadripolar LV lead. Demographic and clinical data were collected
      preoperatively, and patients were followed up for 18.9 months. RESULTS: The
      implantation success rate was 100 %. Mean overall duration was 100.1 +/- 34.6
      min, and X-ray exposure time was 13.20 +/- 13.5 min. The most distal effective
      pacing site was used as the final pacing configuration in all patients. Acute
      dislodgment requiring reoperation occurred before discharge in three cases (6.6
      %). Six patients (13 %) suffered PNS during follow-up; we solved this problem by
      changing the stimulation vector. Three months after implantation, a mean of six
      out of ten effective sites (threshold <2.5 V at 1.5 ms, no PNS) per patient was
      recorded. CONCLUSIONS: Over the relatively long term, the quadripolar LV lead was
      associated with excellent pacing thresholds and low rates of dislocation and PNS.

PMID- 24293179
TI  - Findings on magnetic resonance imaging of fascicular ventricular tachycardia.
AB  - BACKGROUND: Idiopathic left ventricular tachycardia (ILVT) with right bundle
      branch block and left axis deviation originates from the left posterior fascicle-
      Purkinje fiber network. Scar-related ventricular tachycardias (VTs) with Purkinje
      fibers as a part of the reentry circuit have also been described in patients with
      structural heart disease. METHODS AND RESULTS: Nine patients with fascicular VT
      (left posterior, n = 8; left anterior, n = 1) with preserved left ventricular
      ejection fraction (60 +/- 10%) underwent cardiac magnetic resonance imaging (MRI)
      including functional analysis and delayed enhancement magnetic resonance imaging
      (DE-MRI). No definite structural abnormalities were detected by DE-MRI in four
      patients. DE-MRI revealed unifocal or multifocal areas of fibrosis or scar in
      three patients corresponding to the regions where typical Purkinje potentials
      guided successful ablation of the sustained fascicular VT. A false tendon
      extending from the free wall to the septum was found in one patient. Moderate
      reduction of left ventricular ejection fraction associated with septal or
      multifocal left ventricular fibrosis was detected in two patients with
      ventricular bigeminy originating from the left posterior fascicle. During the
      follow-up of 29 +/- 22 months after successful catheter ablation in the nine
      patients, one patient with septal fibrosis detected by DE-MRI had VT recurrence
      and received an implantable cardioverter defibrillator. CONCLUSION: Detection of
      local areas of fibrosis or scar by DE-MRI may help to distinguish idiopathic
      fascicular tachycardia from scar-related fascicular VT in patients with preserved
      left ventricular function.

PMID- 24293181
TI  - Capacitation and Ca(2+) influx in spermatozoa: role of CNG channels and protein
      kinase G.
AB  - Cyclic guanosine monophosphate (cGMP) has been recently shown to modulate in
      vitro capacitation of mammalian spermatozoa, but the mechanisms through which it
      influences sperm functions have not been clarified. There are at least two
      targets of cGMP, cyclic nucleotide-gated (CNG) channels and cGMP-dependent
      protein kinase (PKG), involved in several physiological events in mammalian
      spermatozoa. It has been suggested that CNG channels allow the influx of Ca(2+)
      to cytoplasm during capacitation, whereas PKG could trigger a phosphorylation
      pathway which might also, indirectly, mediate calcium entry. Using the patch
      clamp technique in whole-cell configuration, we showed how l-cis-Diltiazem (a CNG
      channel inhibitor) and KT5823 (a PKG inhibitor) decreased significantly the
      amplitude of macroscopic ion currents in a dose-response manner, and decreased in
      vitro capacitation. The inhibition of CNG channels completely abolishes the
      Ca(2+) influx induced by cyclic nucleotides in mouse spermatozoa. This work
      suggests that the downstream cGMP pathway is required in mammalian sperm
      capacitation and the mechanisms involved include CNG channels and PKG,
      highlighting these molecules as important therapeutic targets for infertility
      treatments or to develop new male contraceptives. 

PMID- 24293180
TI  - Information for physicians and pharmacists about drugs that might cause dry
      mouth: a study of monographs and published literature.
AB  - BACKGROUND: Over three-quarters of the older population take medications that can
      potentially cause dry mouth. Physicians or pharmacists rarely inform patients
      about this adverse effect and its potentially severe damage to the teeth, mouth
      and general health. OBJECTIVES: The objectives of this study were to (1) identify
      warnings in the literature about dry mouth associated with the most frequently
      prescribed pharmaceutical products in Canada; and (2) consider how this
      information might be obtained by physicians, pharmacists and patients. METHODS:
      Monographs on the 72 most frequently prescribed medications during 2010 were
      retrieved from the Compendium of Pharmaceuticals and Specialties (CPS, a standard
      drug information reference for physicians and pharmacists), the National Library
      of Medicine's 'DailyMed' database, directly from the manufacturers, and from a
      systematic search of biomedical journals. RESULTS: The CPS provided monographs
      for 43% of the medications, and requests to manufacturers produced the remaining
      monographs. Mentions of dry mouth were identified in 61% of the products (43%
      amongst CPS monographs; an additional 43% amongst manufacturers' monographs; 7%
      in the DailyMed database and 7% from biomedical journals); five medications had
      contradictory reports in different monographs. CONCLUSION: Nearly two-thirds
      (61%) of the most commonly prescribed medications can cause dry mouth, yet
      warnings about this adverse effect and its potentially serious consequences are
      not readily available to physicians, pharmacists, dentists or patients.

PMID- 24293182
TI  - Characterization and structural analysis of hepcidin like antimicrobial peptide
      from Schizothorax richardsonii (Gray).
AB  - Innate immune system is a primary line of defense in fish that protects it from
      the invading pathogens. Antimicrobial peptides (AMPs) are widely distributed in
      nature and are essential components of innate immunity. These molecules enable
      the host's innate immune system to fight against a variety of infectious agents.
      One such AMP, hepcidin, is a cysteine rich amphipathic peptide. We have
      amplified, cloned and characterized hepcidin like AMP from Schizothorax
      richardsonii that inhabits one of the most difficult aquatic ecosystems in the
      Indian Himalayas. The cDNA encoding hepcidin like peptide was amplified as a 371
      bp fragment with an open reading frame (ORF) of 279 nucleotides flanked by 5' and
      3' UTRs of 70 and 22 bases respectively. This ORF encodes a peptide of 93 amino
      acids with a signal peptide of 24 amino acids and a mature peptide of 25 amino
      acids. The mature hepcidin like peptide of S. richardsonii has eight cystine
      residues that participate in the formation of four disulfide bonds, a unique
      feature of hepcidin like AMPs. A 3D model of hepcidin like mature peptide was
      generated using Modeller 9.10 which was validated using PROCHECK and ERRAT.
      Phylogenetic analysis of hepcidin like AMP from S. richardsonii revealed that it
      was closely related to hepcidin from olive barb (Puntius sarana). 

PMID- 24293183
TI  - Age-related changes in stem cell dynamics, neurogenesis, apoptosis, and gliosis
      in the adult brain: a novel teleost fish model of negligible senescence.
AB  - Adult neurogenesis, the generation of new neurons in the adult central nervous
      system, is a reported feature of all examined vertebrate species. However, a
      dramatic decline in the rates of cell proliferation and neuronal differentiation
      occurs in mammals, typically starting near the onset of sexual maturation. In the
      present study, we examined possible age-related changes associated with adult
      neurogenesis in the brain of brown ghost knifefish (Apteronotus leptorhynchus), a
      teleost fish distinguished by its enormous neurogenic potential. Contrary to the
      well-established alterations in the mammalian brain during aging, in the brain of
      this teleostean species we could not find evidence for any significant age
      related decline in the absolute levels of stem/progenitor cell proliferation,
      neuronal and glial differentiation, or long-term survival of newly generated
      cells. Moreover, there was no indication that the amount of glial fibrillary
      acidic protein or the number of apoptotic cells in the brain was altered
      significantly over the course of adult life. We hypothesize that this first
      demonstration of negligible cellular senescence in the vertebrate brain is
      related to the continued growth of this species and to the lack of reproductive
      senescence during adulthood. The establishment of the adult brain of this species
      as a novel model of negligible senescence provides new opportunities for the
      advancement of our understanding of the biology of aging and the fundamental
      mechanisms that underlie senescence in the brain.

PMID- 24293184
TI  - Emotional eating moderates the relationship of night eating with binge eating and
      body mass.
AB  - Night eating syndrome is marked by substantial evening or nocturnal food intake,
      insomnia, morning anorexia, and depressed mood. Night eating severity has been
      positively associated with body mass index (BMI), binge eating frequency, and
      emotional eating tendencies. We conducted an online questionnaire study among
      students (N=729) and explored possible interactive effects between those
      variables. Night eating severity, binge eating frequency, BMI and emotional
      eating were all positively correlated with each other. Regression analyses showed
      that night eating severity was particularly related to more frequent binge
      episodes and higher BMI at high levels of emotional eating but unrelated to those
      variables at low levels of emotional eating. Thus, eating as a means of emotion
      regulation appears to be an important moderator of the relationship between night
      eating and both binge eating and BMI.

PMID- 24293185
TI  - The duodenal-jejunal bypass liner for the treatment of type 2 diabetes mellitus
      and/or obesity: a systematic review.
AB  - This systematic literature review applies the GRADE approach to evaluate the
      efficacy and safety of the duodenal-jejunal bypass liner (DJBL) for the treatment
      of (a) patients with obesity >= grade II (with comorbidities) and (b) patients
      with type 2 diabetes mellitus + obesity >= grade I. We included ten studies with
      a total of 342 patients that primarily investigated a prototype of the DJBL. In
      high-grade obese patients, short-term excess weight loss was observed. For the
      remaining patient-relevant endpoints and patient populations, evidence was either
      not available or ambiguous. Complications (mostly minor) occurred in 64-100% of
      DJBL patients compared to 0-27% in the control groups. Gastrointestinal bleeding
      was observed in 4% of patients. We do not yet recommend the device for routine
      use.

PMID- 24293186
TI  - Roles of the PDZ domain-binding motif of the human papillomavirus type 16 E6 on
      the immortalization and differentiation of primary human foreskin keratinocytes.
AB  - A number of PDZ domain-containing proteins have been identified as binding
      partners for the oncoprotein E6 of the high-risk type human papillomaviruses
      (HPVs). These include hDlg, hScrib, MAGI1, MAGI2, and MAGI3, MUPP1, 14-3-3zeta,
      Na/H exchange regulatory factor 1, PTPN13, TIP-2/GIPC, Tip-1, and PATJ. The PDZ
      domain-binding motif (-X-T-X-V) at the carboxy terminus of E6 is essential for
      targeting PDZ proteins for proteasomal degradation. However, contribution of
      degradation of PDZ proteins by E6 to HPV-induced oncogenesis is still
      controversial. In order to clarify potential roles of molecular interactions
      between high-risk HPV E6 and one of best characterized PDZ proteins, hDlg in HPV
      induced transformation, we used a retroviral infection system to overexpress
      HPV16 E7 gene alone or together with either HPV16 E6 wild type or E6 mutant gene
      lacking the PDZ domain-binding motif and investigated the effect of mutating the
      PDZ domain-binding motif of E6 on the immortalization and differentiation of
      human foreskin keratinocytes (HFKs) by the high-risk type HPV E6 and E7. Although
      the PDZ domain-binding motif of E6 was found to be required for the efficient
      growth of HFKs, it was not necessary for the E6 and E7-induced immortalization of
      HFKs. Furthermore, the overexpression of E6 and E7 neither induced degradation
      nor altered cellular localization of hDlg in undifferentiated or differentiated
      HFKs. These data indicate that the PDZ domain-binding motif of E6 contributes to
      the efficient cellular growth through mechanisms other than degradation and
      changes in the subcellular localizations of hDlg.

PMID- 24293187
TI  - Substrate modification by adding ablation of localized complex fractionated
      electrograms after stepwise linear ablation in persistent atrial fibrillation.
AB  - PURPOSE: Linear left atrial (LA) ablation in patients with persistent atrial
      fibrillation (PsAF) resulting in the elimination of most complex fractionated
      electrogram (CFE) sites has been demonstrated. This study was designed to
      evaluate the impact of a localized CFE ablation in addition to a representative
      linear LA ablation in patients with PsAF. METHODS: A total of 40 consecutive
      patients with PsAF underwent construction of CFE and dominant frequency (DF) maps
      using NavX. A stepwise linear ablation including at the PV antra, septum, roof,
      mitral annulus, and ridge of the appendage was performed followed by additional
      ablation of localized CFEs detected by an automatic algorithm. RESULTS: A
      significant reduction in the continuous CFE burden (<50 ms) after the linear
      ablation (69 vs. 21 %; P < 0.0001) was confirmed, and localized CFEs (40-120 ms)
      were observed with a significant predilection for the anterior (30 %), posterior
      (30 %), and inferior LA (38 %) regions (P < 0.01). Comparing the localized CFEs
      with higher frequency sources, 45 % (70/156) of the localized CFE sites included
      continuous CFE regions, and 59 % (92/156) of those sites overlapped with the high
      DF sites (>8 Hz). Additional localized CFE-targeted ablation further terminated
      PsAF in 20 % of the patients and further increased the mean CFE cycle length (110
      +/- 31 to 125 +/- 39 ms; P = 0.0033) and decreased the DF (6.0 +/- 0.8 to 5.7 +/-
      0.7 Hz; P = 0.0013) within the CS. CONCLUSIONS: The presence of localized CFE
      sites with a predilection for particular LA regions after a representative linear
      LA ablation could provide the optimal sites for selective substrate modification
      of the atrial fibrillation substrate in patients with PsAF.

PMID- 24293188
TI  - Antimicrobial activity of nisin, thymol, carvacrol and cymene against growth of
      Candida lusitaniae.
AB  - Yeasts are tolerant to acid pH values, are able to grow in anaerobic media and
      have minimum nutrition requirements. These capabilities enable them to survive
      and even grow in foods prepared from acid fruits or vegetables. Among yeasts,
      Candida is one of the genus most frequently isolated from fruit juices.
      Bacteriocins and essential oils from spices and aromatic herbs are an alternative
      to preservatives and other technological treatments and have the advantage that
      their natural origins do not lead to consumer rejection. However, before the food
      industry uses them on a large scale, it is necessary to know their effects on
      microorganisms. The objective of this research was to study the effect of
      different concentrations of nisin, thymol, carvacrol and cymene on the growth of
      Candida lusitaniae in pH 5 broth at 25 C, and their potential uses as food
      preservatives. The addition of nisin at the concentrations tested (up to 3 umol
      L(-1)) did not affect the yeast growth. Thymol, carvacrol and cymene completely
      inhibited the yeast growth at concentrations over 1 mM for at least 21 days at 25
      C. Below this concentration, inhibitions on yeast growth were observed at
      increasing concentrations. The effect of thymol was also proved in tomato juice.
      This study indicates the potential use of essential oils for preservation of
      minimally processed foods. 

PMID- 24293189
TI  - Postnatal changes in the number of serotonin-immunoreactive cells in midbrain
      raphe nuclei of male rats.
AB  - To clarify the developmental changes in serotonergic neurons in the subdivisions
      of the dorsal (DR) and median raphe (MR) nuclei before puberty, the extent of the
      nuclei and the number of serotonin (5-HT) immunoreactive (ir) cells were measured
      in 5-, 15-, and 30-day-old rats and 8-week-old (adult) castrated male rats. The
      brains were fixed and 50 MUm frozen sections prepared. After immunostaining for 5
      HT, the number of 5-HT-ir cells in a 0.2 * 0.2 mm frame in the dorsal, ventral
      and lateral subdivisions of the DR (dDR, vDR and lDR, respectively) and MR were
      counted. Total numbers of 5-HT-ir cells counted in the frame of three sections in
      each rat were expressed as the number of cells per cubic millimeter (density).
      The results indicated that the densities of 5-HT-ir cells in the MR were almost
      the same in all age groups. On the other hand, among the subdivisions of the DR,
      the mean density of 5-HT-ir cells in 15-day-old rats was higher than that in the
      5-day-old group in the lDR only. The area of the three sections of the DR and of
      the MR was also measured. The area of the DR in 15-day-old rats was found to be
      twice that in the 5-day-old rats, and differed from the area in 30-day-old rats
      and adults. There were no differences among the age groups in the areas of the
      MR. The results indicate that the expression of 5-HT in the lDR and extent of the
      DR increased to adult levels from days 5 to 15 after birth. In the dDR, vDR and
      MR, expression of 5-HT at postnatal day 5 was at adult levels already. 

PMID- 24293190
TI  - Managing humiliation.
AB  - This paper reviews findings concerning ways that people have found to minimize or
      avoid humiliation. It concludes with a discussion of addressing the task of
      creating humiliation-free institutions. 

PMID- 24293192
TI  - Foreword: Veneto Dialysis and Transplantation Registry, 2008-2010 report.

PMID- 24293191
TI  - Enhancement of peripheral nerve regeneration due to treadmill training and
      electrical stimulation is dependent on androgen receptor signaling.
AB  - Moderate exercise in the form of treadmill training and brief electrical nerve
      stimulation both enhance axon regeneration after peripheral nerve injury.
      Different regimens of exercise are required to enhance axon regeneration in male
      and female mice (Wood et al.: Dev Neurobiol 72 (2012) 688-698), and androgens are
      suspected to be involved. We treated mice with the androgen receptor blocker,
      flutamide, during either exercise or electrical stimulation, to evaluate the role
      of androgen receptor signaling in these activity-based methods of enhancing axon
      regeneration. The common fibular (CF) and tibial (TIB) nerves of thy-1-YFP-H
      mice, in which axons in peripheral nerves are marked by yellow fluorescent
      protein (YFP), were transected and repaired using CF and TIB nerve grafts
      harvested from non-fluorescent donor mice. Silastic capsules filled with
      flutamide were implanted subcutaneously to release the drug continuously.
      Exercised mice were treadmill trained 5 days/week for 2 weeks, starting on the
      third day post-transection. For electrical stimulation, the sciatic nerve was
      stimulated continuously for 1 h prior to nerve transection. After 2 weeks,
      lengths of YFP+ profiles of regenerating axons were measured from harvested
      nerves. Both exercise and electrical stimulation enhanced axon regeneration, but
      this enhancement was blocked completely by flutamide treatments. Signaling
      through androgen receptors is necessary for the enhancing effects of treadmill
      exercise or electrical stimulation on axon regeneration in cut peripheral nerves.

PMID- 24293193
TI  - Incidence of renal replacement therapy in Veneto for 2008, 2009 and 2010.
AB  - This section of the report of the Veneto Dialysis and Transplantation Registry
      (VDTR) provides data on the incidence of patients receiving renal replacement
      therapy (RRT) in the region from 2008 to 2010. Its purpose is to provide health
      authorities with the information they need to plan the delivery of RRT in Veneto.
      Data were obtained from the VDTR, defining incident patients according to the
      recommendations of the Italian Dialysis and Transplantation Registry. The
      incidence rate was calculated per million population (pmp). Variability by
      province and treatment center was studied by applying multilevel modeling
      methods. An age-period-cohort model was used to forecast the incidence rate of
      RRT over the years to come. The incidence of patients on RRT was 114.23 pmp in
      2008, 120.15 pmp in 2009 and 107.08 pmp in 2010. The patients' median age at the
      time of starting RRT was 70.5 in 2008, 68.7 in 2009 and 69.5 in 2010. During
      these 3 years, 66.3% of patients were male, and 33.7% were female. Incidence
      rates were not uniformly distributed between the provinces in the region, but
      were significantly higher in 2. The incidence rate of patients needing RRT seems
      likely to remain stable in the future, until 2015 at least. Renal vascular
      disease was the primary cause of end-stage renal disease (ESRD), followed closely
      by diabetes, while the proportion due to primary glomerulonephritis has gradually
      decreased. Initial dialysis modality was hemodialysis (HD) for 78% of patients,
      while about 20% started RRT on peritoneal dialysis (PD), and a negligible
      proportion had a preemptive kidney transplantation. About 35% patients began
      dialysis with a temporary vascular catheter; this percentage remained fairly
      constant until 2010. The incidence of RRT in Veneto is one of the lowest in Italy
      and remained substantially stable over the period 1998-2010, despite the
      population of patients with ESRD becoming older and more severely ill. This
      finding could mean a heavier burden on the welfare system in the future.

PMID- 24293194
TI  - Prevalence of renal replacement therapy in Veneto for 2008, 2009 and 2010.
AB  - The aim of this section is to provide descriptive data for end-stage renal
      disease (ESRD) in the Veneto Region (Italy). Data were obtained from the Veneto
      Dialysis and Transplantation Registry (VDTR). Patients were considered to be
      prevalent renal replacement therapy (RRT) patients if alive on 31 December of
      each year examined. Prevalence is expressed per million population (pmp). The
      trend for prevalence of each treatment in the period examined was estimated by
      random effects longitudinal logistic regression. Prevalence of RRT in Veneto in
      the years 2008, 2009 and 2010 was 888, 923 and 950 pmp, respectively. The
      prevalence of RRT patients by treatment modality showed a slight increase for
      hemodialysis, notable stability for peritoneal dialysis and a more pronounced
      increase for transplantation. Every year, about 10% of peritoneal dialysis
      patients shifted to hemodialysis, and 12% received a transplant. The transition
      probability from hemodialysis to peritoneal dialysis was negligible, and less
      than 5% of hemodialysis patients received a transplant. The probability of
      returning to hemodialysis after having received a transplant was less than 2% a
      year. Bicarbonate hemodialysis slowly increased from 1998 to 2010, both in
      percentage and in prevalence per million population; conversely,
      hemodiafiltration (HDF) showed a mild but constant decrease. Automated peritoneal
      dialysis (APD), which was quantitatively almost negligible in 1998, reached the
      same level as continuous ambulatory peritoneal dialysis (CAPD) in 2010. The
      prevalence of patients undergoing living donor transplants almost doubled in the
      period 1998-2010. The increase of prevalence over time was not proportional for
      the 3 modalities of RRT: hemodialysis prevalence grew slowly, peritoneal dialysis
      prevalence remained stable, and renal transplant prevalence quickly increased.

PMID- 24293195
TI  - Mortality in the Veneto population on renal replacement therapy.
AB  - This section reports survival rates for patients on renal replacement therapy
      (RRT). The data obtained from the Veneto Dialysis and Transplantation Registry
      (VDTR) cover the whole population in the region. Patients on RRT alive on 31
      December of each year were assumed to be at risk of dying in the following year.
      Furthermore, time-to-event analysis was used to describe the complete history of
      patients from when they started RRT until they died, including transitions
      between the 3 main treatment modalities - hemodialysis (HD), peritoneal dialysis
      (PD) and renal transplantation. The cohort of patients starting RRT from 1998 to
      2010 was followed up until 31 December 2010. Survival rates from the first
      treatment to death were calculated according to the life table method. Relative
      survival and excess mortality rates were estimated according to the Ederer II
      method. A multistate model was used to describe changes in a patient's condition
      (changes of treatment, or death) over time. Among prevalent patients on RRT, the
      annual risk of death was 10.65% in 2008, 9.35% in 2009 and 8.86% in 2010. The
      overall mortality rate was 12.5 per 100 patient-years (95% confidence interval
      [95% CI], 12.1-13.0). The 5-year relative survival was 59% (95% CI, 57%-60%), and
      at 10 years relative survival was 41% (95% CI, 39%-43%); the estimated excess
      mortality rate was very high at the start of RRT (18 per 100 patient-years) but
      gradually decreased after the second year. On multivariate analysis, excess
      mortality was associated with age and primary renal diseases. Less than 10% of
      patients starting on PD shifted to HD in the first year of RRT, and a
      considerable proportion received a transplant, amounting to 6% in the first year,
      and thereafter increasing steadily: at the end of the fifth year, 34% of patients
      starting RRT on PD had received a transplant. HD patients behaved differently:
      any shift to PD was negligible, and the patients receiving a transplant amounted
      to only 2% in the first year and about 16% by the end of the fifth year.
      Cumulative mortality among HD patients was particularly high (already 18% at 1
      year, and 70% at 10 years) by comparison with those on PD (8% at 1 year, 54% at
      10 years). Although mortality on RRT is not particularly high in Veneto by
      comparison with countries other than Italy, this result is mainly due to an
      increasing number of patients receiving transplants, which makes them a favorably
      selected population. The mortality rate was high among those on HD, particularly
      in the first year. Our population on RRT is rather heterogeneous, and a
      description of the outcomes based only on the whole population may be misleading.

PMID- 24293196
TI  - Eusociality: from the first foragers to the first states. Introduction to the
      special issue.
AB  - People have always been social. Ethnographic evidence suggests that transfers of
      food and labor are common among contemporary hunter-gatherers, and they probably
      were common in Paleolithic groups. Archaeological evidence suggests that
      cooperative breeding went up as we settled down: as territory defenders became
      more successful breeders, their helpers' fertility would have been delayed or
      depressed. And written evidence from the Neolithic suggests that the first
      civilizations were often eusocial; emperors fathered hundreds of children, who
      were provided for and protected by workers in sterile castes. Papers in this
      issue of Human Nature look at helpers and workers across the eusociality
      continuum--from hard-working grandmothers and grandfathers, to celibate sisters
      and brothers, to castrated civil servants--from the first foragers to the first
      states.

PMID- 24293197
TI  - Comparative and cost effectiveness of treatment modalities for hepatocellular
      carcinoma in SEER-Medicare.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing in the
      USA and worldwide. Several treatments are available for patients diagnosed at any
      disease stage. It remains unclear how medical expenditures vary across patients
      who remain untreated or undergo different modes of therapy. We evaluate the
      comparative and cost effectiveness of treatment modalities for HCC from a
      Medicare perspective. METHODS: The Surveillance, Epidemiology, and End Results
      (SEER) registries and linked Medicare database with claims from Parts A/B were
      used to identify Medicare enrollees with initial diagnosis of HCC between 2000
      and 2007 and followed through 2009. Patients were assigned to treatment
      modalities based on HCC staging systems: transplant, resection, liver directed,
      radiation, chemotherapy or no treatment. Survival benefits and cumulative
      Medicare expenditures were estimated in multivariate models, stratified by
      initial disease stage, to control for confounding. Cost-effectiveness ratios
      compared costs and benefits of the modalities across initial stages. RESULTS:
      Cancer stages I, II, III, IV and unstaged represented 24, 9, 14, 17 and 37 % of
      11,047 patients, respectively. Fewer than 40 % received any treatment. Relative
      to no treatment, transplant was most effective in reducing mortality, followed by
      resection, liver directed, and radiation or chemotherapy. Resection tended to be
      most cost effective in early staged and unstaged patients; transplant was least
      cost effective. In stage IV patients, liver directed therapy was more cost
      effective than chemotherapy or radiation. CONCLUSIONS: Survival benefit was
      attributable to all treatment modalities. More effective treatments incurred
      greater Medicare expenditures, but resection patients incurred the least
      expenditures per year of life gained.

PMID- 24293198
TI  - The value of a QALY: individual willingness to pay for health gains under risk.
AB  - BACKGROUND: There is an increased interest in the monetary value of a quality
      adjusted life-year (QALY). Past studies commonly derived willingness to pay (WTP)
      for certain future QALY gains. However, obtaining valid WTP per QALY estimates
      proved to be difficult. OBJECTIVE: We conducted a contingent valuation study and
      estimated the individual WTP per QALY under risk. We demonstrate the impact of
      probability weighting on WTP per QALY estimates in the Netherlands. RESULTS: Our
      estimates of the value of a QALY are in the range of ?80,000-110,000 when the
      weighting correction was applied, and ?250,500 without correction. The validity
      of these estimates, applying probability weighting, appears to be good.
      CONCLUSIONS: Given the reasonable support for their validity and practical
      meaningfulness, the estimates derived while correcting for probability weighting
      may provide valuable input for the debate on the consumption value of health.
      While decision makers should not apply these estimates without further
      consideration, since strictly individual valuations may not carry all relevant
      information and values for societal decision-making, the current estimates may
      provide a good and informed basis for further discussion and study of this
      important topic.

PMID- 24293199
TI  - Critical theory as an approach to the ethics of information security.
AB  - Information security can be of high moral value. It can equally be used for
      immoral purposes and have undesirable consequences. In this paper we suggest that
      critical theory can facilitate a better understanding of possible ethical issues
      and can provide support when finding ways of addressing them. The paper argues
      that critical theory has intrinsic links to ethics and that it is possible to
      identify concepts frequently used in critical theory to pinpoint ethical
      concerns. Using the example of UK electronic medical records the paper
      demonstrates that a critical lens can highlight issues that traditional ethical
      theories tend to overlook. These are often linked to collective issues such as
      social and organisational structures, which philosophical ethics with its typical
      focus on the individual does not tend to emphasise. The paper suggests that this
      insight can help in developing ways of researching and innovating responsibly in
      the area of information security. 

PMID- 24293200
TI  - Global chain properties of an all l-alpha-eicosapeptide with a secondary alpha
      helix and its all retro d-inverso-alpha-eicosapeptide estimated through the
      modeling of their CZE-determined electrophoretic mobilities.
AB  - Several global chain properties of relatively long peptides composed of 20 amino
      acid residues are estimated through the modeling of their experimental effective
      electrophoretic mobilities determined by CZE for 2 < pH < 6. In this regard, an
      all l-alpha-eicosapeptide, including a secondary alpha-helix (Peptide 1) and its
      all retro d-inverso-alpha-eicosapeptide (Peptide 2), are considered. Despite
      Peptides 1 and 2 are isomeric chains, they do not present similar global
      conformations in the whole range of pH studied. These peptides may also differ in
      the quality of BGE components chain interactions depending on the pH value. Three
      Peptide 1 fragments (Peptides 3, 4, and 5) are also analyzed in this framework
      with the following purposes: (i) visualization of the effects of initial and
      final strands at each side of the alpha-helix on the global chain conformations
      of Peptide 1 at different pHs and (ii) analysis of global chain conformations of
      Peptides 1 and 2, and Peptide 1 fragments in relation to their pI values. Also,
      the peptide maximum and minimum hydrations predicted by the model, compatible
      with experimental effective electrophoretic mobilities at different pHs, are
      quantified and discussed, and needs for further research concerning chain
      hydration are proposed. It is shown that CZE is a useful analytical tool for
      peptidomimetic designs and purposes. 

PMID- 24293201
TI  - Effect of contrast leakage on the detection of abnormal brain tumor vasculature
      in high-grade glioma.
AB  - Abnormal brain tumor vasculature has recently been highlighted by a dynamic
      susceptibility contrast (DSC) MRI processing technique. The technique uses
      independent component analysis (ICA) to separate arterial and venous perfusion.
      The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially
      occurs in brain tumors and predicts response to anti-angiogenic therapy. The
      effects of contrast agent leakage on the AVOL biomarker have yet to be
      established. DSC was acquired during two separate contrast boluses in ten
      patients undergoing clinical imaging for brain tumor diagnosis. Three components
      were modeled with ICA, which included the arterial and venous components. The
      percentage of each component as well as a third component were determined within
      contrast enhancing tumor and compared. AVOL within enhancing tumor was also
      compared between doses. The percentage of enhancing tumor classified as not
      arterial or venous and instead into a third component with contrast agent leakage
      apparent in the time-series was significantly greater for the first contrast dose
      compared to the second. The amount of AVOL detected within enhancing tumor was
      also significantly greater with the second dose compared to the first. Contrast
      leakage results in large signal variance classified as a separate component by
      the ICA algorithm. The use of a second dose mitigates the effect and allows
      measurement of AVOL within enhancement. 

PMID- 24293202
TI  - The association between cytokines and insulin sensitivity in Iraqi immigrants and
      native Swedes.
AB  - OBJECTIVES: To investigate the associations between cytokines and insulin
      sensitivity in Swedish residents born in Iraq and Swedish residents born in
      Sweden. DESIGN: Cross-sectional study. SETTINGS: Iraqi and Swedish origin
      residents of Rosengard area of Malmo, aged 45-65 years, were randomly selected
      from the census register. PARTICIPANTS/METHODS: 194 (Iraqi, n=107; Swedish, n=87)
      participants agreed to participate in the study. Nineteen participants dropped
      out (Iraqi, n=11; Swedish, n=8). Participants who had already been diagnosed with
      type 2 diabetes mellitus (T2DM), those who could not participate in an oral
      glucose tolerance test and those who had a cold/fever at the time of blood
      sampling were excluded. In total, serum samples from 135 individuals of Swedish
      (n=62) and Iraqi (n=73) origin were included. Serum concentrations of a panel of
      10 cytokines, comprising interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10,
      IL-12 (p70), IL-13, interferon-gamma and tumour necrosis factor-alpha were
      analysed by Luminex multiplex assay. RESULTS: In the whole study population,
      levels of all tested cytokines were inversely associated with insulin sensitivity
      index (ISI), independent of age, sex, body mass index (BMI), sedentary lifestyle
      and family history of T2DM (p <= 0.05). Interestingly, stratification of the
      study population according to country of birth showed a significant inverse
      association between all tested cytokines and ISI in the Iraqi-born population (p
      <= 0.01). The association was independent of age, sex, BMI, sedentary lifestyle
      and family history of T2DM. In contrast, with the exception for IL-6 (p=0.05), no
      other tested cytokine was found to be significantly associated with ISI in the
      Swedish-born population (p>=0.05). CONCLUSIONS: Our results show an association
      between cytokines and ISI in the Iraqi-born population but not in the Swedish
      born population.

PMID- 24293203
TI  - Mindfulness online: an evaluation of the feasibility of a web-based mindfulness
      course for stress, anxiety and depression.
AB  - OBJECTIVES: Face-to-face mindfulness interventions have been shown to
      significantly decrease perceived stress, anxiety and depression and research is
      beginning to show similar benefits for such courses delivered via the internet.
      We investigated the feasibility and effectiveness of an online mindfulness course
      for perceived stress, anxiety and depression. DESIGN: A follow-up investigation
      of an online mindfulness course. Previous research examining the change in
      perceived stress showed promising results. Measures of anxiety and depression
      were added to the online mindfulness course and these were investigated as well
      as perceived stress using a new, larger sample. PARTICIPANTS: Participants
      (N=273) were self-referrals to the online course who completed the outcome
      measure immediately before the course, upon course completion and at 1 month
      follow-up. INTERVENTION: The programme consists of 10 sessions, guided meditation
      videos and automated emails, with elements of Mindfulness-Based Stress Reduction
      and Mindfulness-Based Cognitive Therapy, completed at a pace to suit the
      individual (minimum length 4 weeks). PRIMARY AND SECONDARY OUTCOME MEASURES: The
      Perceived Stress Scale, the Generalised Anxiety Disorder Assessment-7 and the
      Patient Health Questionnaire-9 (for depression). Mindfulness practice was self
      reported at automated time points upon login, once the exercises and sessions for
      each week were completed. RESULTS: Perceived stress, anxiety and depression
      significantly decreased at course completion and further decreased at 1 month
      follow-up, with effect sizes comparable to those found with face-to-face and
      other online mindfulness courses and to other types of intervention, such as
      cognitive behavioural therapy for stress. The amount of meditation practice
      reported did affect outcome when controlling for baseline severity. CONCLUSIONS:
      The online mindfulness course appears to be an acceptable, accessible
      intervention which reduces stress, anxiety and depression. However, there is no
      control comparison and future research is required to assess the effects of the
      course for different samples.

PMID- 24293204
TI  - The relationship between suicidal ideation and symptoms of depression in Japanese
      workers: a cross-sectional study.
AB  - OBJECTIVES: The prevalence of suicidal ideation and predictors for suicidal
      ideation among Japanese workers is unknown, although a previous study reported a
      30% prevalence rate of suicidal ideation in a psychosomatic clinical setting.
      Hence, we evaluated the prevalence of suicidal ideation and its relationship with
      depressive symptoms among Japanese workers. METHODS: For this purpose, a cross
      sectional design was used. Major depressive disorder (MDD) and suicidal ideation
      in 1266 workers (1100 men and 166 women, aged 20-69 years) were assessed through
      clinical interviews conducted in accordance with the fourth edition of the
      Diagnostic and Statistical Manual of Mental Disorders. RESULTS: A total of 34 and
      70 participants were diagnosed with suicidal ideation and MDD, respectively.
      Suicidal ideation was especially prevalent in 40-year-olds to 49-year-olds. Six
      of the eight symptoms of MDD (depressive mood, loss of interest, weight loss,
      psychomotor agitation, worthlessness and concentration loss) were related to
      suicidal ideation. Depressive mood had the strongest relationship with suicidal
      ideation, followed by worthlessness and concentration loss. Worthlessness had the
      highest area under the curve in predicting suicidal ideation, followed by
      concentration loss and depressive mood. CONCLUSIONS: We conclude that MDD
      symptoms-particularly depressive mood, worthlessness and concentration loss-are
      potential predictors of suicidal ideation in Japanese workers.

PMID- 24293205
TI  - Herbal medicines for the treatment of acute otitis media: protocol for a
      systematic review.
AB  - INTRODUCTION: The aim of this systematic review is to analyse the trial data on
      the efficacy of herbal medicines for acute otitis media. METHODS AND ANALYSIS:
      The following 11 databases will be searched from their inception: MEDLINE, the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Allied
      and Complementary Medicine Database (AMED), the Cochrane Central Register of
      Controlled Trials (CENTRAL), China Network Knowledge Infrastructure (CNKI) and
      five Korean databases (Oriental Medicine Advanced Searching Integrated System
      (OASIS), DBPIA, KoreaMed, Research Information Service System (RISS) and the
      Korean Studies Information Service System (KISS)). The selection of the studies,
      the data abstraction and the validations will be performed independently by two
      researchers. DISSEMINATION: The systematic review will be published in a peer
      reviewed journal. The review will also be disseminated electronically and in
      print. Updates of the review will be conducted to inform and guide the healthcare
      practice and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2013:CRD42013005100.

PMID- 24293206
TI  - Knowledge, attitudes and practices regarding infant feeding among HIV-infected
      pregnant women in Gaborone, Botswana: a cross-sectional survey.
AB  - OBJECTIVES: To assess knowledge, attitudes and practices regarding infant feeding
      among HIV-positive pregnant women in Gaborone, Botswana, and factors that
      influence their infant feeding choices. DESIGN: A cross-sectional study. METHODS
      AND STUDY SETTING: A questionnaire survey of 96 HIV-positive pregnant women
      attending four public infectious disease control clinics in Gaborone, Botswana.
      RESULTS: Only about half of the study participants had knowledge about prevention
      of mother-to-child transmission (PMTCT) services related to breastfeeding, and
      very few (19.8%) chose to breastfeed their infants exclusively. Results of
      multiple logistic regression analysis showed that receiving infant feeding
      counselling as part of the PMTCT programme was significantly associated with a
      decision to exclusively breastfeed (OR (95% CI) 5.38 (1.83 to 15.81)). Similarly,
      HIV-positive pregnant women who received breastfeeding counselling through the
      PMTCT programme had higher knowledge of PMTCT practices related to appropriate
      infant feeding (OR (95% CI) 5.91 (1.06 to 34.31)). Women who did not express
      concern about HIV stigma had significantly higher knowledge of PMTCT practices
      related to infant feeding (OR (95% CI) 5.91 (1.69 to 15.56)). Knowledge of PMTCT
      practices related to breastfeeding was negatively associated with the belief that
      breastfeeding could transmit HIV to the baby (OR (95% CI) 9.73 (3.37 to 28.08)).
      CONCLUSIONS: Knowledge, attitudes and practices related to breastfeeding among
      HIV-positive pregnant women need further improvement, and the PMTCT programme
      should strengthen infant feeding counselling services to assist HIV-positive
      mothers in making informed and appropriate decisions regarding infant feeding.

PMID- 24293207
TI  - Famine in childhood and postmenopausal coronary artery calcification: a cohort
      study.
AB  - OBJECTIVE: To assess the effects of famine exposure during childhood on coronary
      calcium deposition and, secondarily, on cardiac valve and aortic calcifications.
      DESIGN: Retrospective cohort. SETTING: Community. PATIENTS: 286 postmenopausal
      women with individual measurements of famine exposure during childhood in the
      Netherlands during World War II. INTERVENTION/EXPOSURE: Famine exposure during
      childhood. MAIN OUTCOME MEASURES: Coronary artery calcifications measured by CT
      scan and scored using the Agatston method; calcifications of the aorta and
      cardiac valves (mitral and/or aortic) measured semiquantitatively. Logistic
      regression was used for coronary Agatston score of >100 or <=100, valve or aortic
      calcifications as the dependent variable and an indicator for famine exposure as
      the independent variable. These models were also used for confounder adjustment
      and stratification based on age groups of 0-9 and 10-17 years. RESULTS: In the
      overall analysis, no statistically significant association was found between
      severe famine exposure in childhood and a high coronary calcium score (OR 1.80,
      95% CI 0.87 to 3.78). However, when looking at specific risk periods, severe
      famine exposure during adolescence was related to a higher risk for a high
      coronary calcium score than non-exposure to famine, both in crude (OR 3.47, 95%
      CI 1.00 to 12.07) and adjusted analyses (OR 4.62, 95% CI 1.16 to 18.43). No
      statistically significant association was found between childhood famine exposure
      and valve or aortic calcification (OR 1.66, 95% CI 0.69 to 4.10). CONCLUSIONS:
      Famine exposure in childhood, especially during adolescence, seems to be
      associated with a higher risk of coronary artery calcification in late adulthood.
      However, the association between childhood famine exposure and cardiac
      valve/aortic calcification is less clear.

PMID- 24293208
TI  - Fear of childbirth predicts postpartum depression: a population-based analysis of
      511 422 singleton births in Finland.
AB  - OBJECTIVES: To study how reproductive risks and perinatal outcomes are associated
      with postpartum depression treated in specialised healthcare defined according to
      the International Classification of Diseases (ICD)-10 codes, separately among
      women with and without a history of depression. DESIGN: A retrospective
      population-based case-control study. SETTING: Data gathered from three national
      health registers for the years 2002-2010. PARTICIPANTS: All singleton births
      (n=511 422) in Finland. PRIMARY OUTCOME MEASURES: Prevalence of postpartum
      depression and the risk factors associated with it. RESULTS: In total, 0.3% (1438
      of 511 422) of women experienced postpartum depression, the prevalence being 0.1%
      (431 of 511 422) in women without and 5.3% (1007 of 18 888) in women with a
      history of depression. After adjustment for possible covariates, a history of
      depression was found to be the strongest risk factor for postpartum depression.
      Other strong predisposing factors for postpartum depression were fear of
      childbirth, caesarean birth, nulliparity and major congenital anomaly.
      Specifically, among the 30% of women with postpartum depression but without a
      history of depression, postpartum depression was shown to be associated with fear
      of childbirth (adjusted OR (aOR 2.71, 95% CI 1.98 to 3.71), caesarean birth (aOR
      1.38, 95% CI 1.08 to 1.77), preterm birth (aOR 1.65, 95% CI 1.08 to 2.56) and
      major congenital anomaly (aOR 1.67, 95% CI 1.15 to 2.42), compared with women
      with no postpartum depression and no history of depression. CONCLUSIONS: A
      history of depression was found to be the most important predisposing factor of
      postpartum depression. Women without previous episodes of depression were at an
      increased risk of postpartum depression if adverse events occurred during the
      course of pregnancy, especially if they showed physician-diagnosed fear of
      childbirth.

PMID- 24293209
TI  - Baggage handler seniority and musculoskeletal symptoms: is heavy lifting in
      awkward positions associated with the risk of pain?
AB  - OBJECTIVES: Heavy lifting is associated with musculoskeletal disorders but it is
      unclear whether it is related to acute reversible effects or to chronic effects
      from cumulated exposure. The aim of this study was to examine whether
      musculoskeletal symptoms in Danish airport baggage handlers were associated with
      their seniority as baggage handler, indicating chronic effects from cumulated
      workload. METHODS: We established a group of baggage handlers employed at
      Copenhagen Airport during the period 1983-2012 (n=3092) and a reference group of
      men in other unskilled occupations with less heavy work (n=2478). Data regarding
      work history, lifestyle and musculoskeletal symptoms were collected using a self
      administered questionnaire (response rate 70.1% among baggage handlers and 68.8%
      among the reference group). RESULTS: The ORs of self-reported musculoskeletal
      symptoms during the last 12 months in the neck/upper back, lower back, shoulders,
      elbows, wrists, hips and knees were significantly higher in baggage handlers than
      in the reference group. These differences were explained by significant linear
      effects of baggage handler seniority for six anatomical regions. Adjustment for
      age, body mass index, smoking and leisure-time physical activity did not change
      these results. The findings were stable over age strata and among present and
      former baggage handlers. CONCLUSIONS: The risk of musculoskeletal symptoms in six
      anatomical regions increased with increasing seniority as a baggage handler. This
      is consistent with the assumption that cumulated heavy lifting may cause chronic
      or long-lasting musculoskeletal symptoms. However, we cannot exclude that other
      factors related to baggage handler seniority may explain some of the
      associations.

PMID- 24293210
TI  - Labile carbon retention compensates for CO2 released by priming in forest soils.
AB  - Increase of belowground C allocation by plants under global warming or elevated
      CO2 may promote decomposition of soil organic carbon (SOC) by priming and
      strongly affects SOC dynamics. The specific effects by priming of SOC depend on
      the amount and frequency of C inputs. Most previous priming studies have
      investigated single C additions, but they are not very representative for
      litterfall and root exudation in many terrestrial ecosystems. We evaluated
      effects of (13)C-labeled glucose added to soil in three temporal patterns:
      single, repeated, and continuous on dynamics of CO2 and priming of SOC
      decomposition over 6 months. Total and (13)C labeled CO2 were monitored to
      analyze priming dynamics and net C balance between SOC loss caused by priming and
      the retention of added glucose-C. Cumulative priming ranged from 1.3 to 5.5 mg C
      g(-1) SOC in the subtropical, and from -0.6 to 5.5 mg C g(-1) SOC in the tropical
      soils. Single addition induced more priming than repeated and continuous inputs.
      Therefore, single additions of high substrate amounts may overestimate priming
      effects over the short term. The amount of added glucose C remaining in soil
      after 6 months (subtropical: 8.1-11.2 mg C g(-1) SOC or 41-56% of added glucose;
      tropical: 8.7-15.0 mg C g(-1) SOC or 43-75% of glucose) was substantially higher
      than the net C loss due to SOC decomposition including priming effect. This
      overcompensation of C losses was highest with continuous inputs and lowest with
      single inputs. Therefore, raised labile organic C input to soils by higher plant
      productivity will increase SOC content even though priming accelerates
      decomposition of native SOC. Consequently, higher continuous input of C
      belowground by plants under warming or elevated CO2 can increase C stocks in soil
      despite accelerated C cycling by priming in soils.

PMID- 24293211
TI  - The effects of cannabidiol and its synergism with bortezomib in multiple myeloma
      cell lines. A role for transient receptor potential vanilloid type-2.
AB  - Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the
      accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol
      (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the
      transient receptor potential vanilloid type-2 (TRPV2) channel has been reported
      as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and
      increases susceptibility to drug-induced cell death in human cancer cells.
      However, no functional role has been ascribed to CBD and TRPV2 in MM. In this
      study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2-
      PC populations in MM patients, whereas only the CD138+ TRPV2- population was
      present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly
      used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2-
      MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These
      results showed that CBD by itself or in synergy with BORT strongly inhibited
      growth, arrested cell cycle progression and induced MM cells death by regulating
      the ERK, AKT and NF-kappaB pathways with major effects in TRPV2+ cells. These
      data provide a rationale for using CBD to increase the activity of proteasome
      inhibitors in MM.

PMID- 24293212
TI  - Anaphylaxis caused by intravenous fluorescein: clinical characteristics and
      review of literature.
AB  - Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that
      suddenly occurs after contact with an allergy-causing substance. The aims of this
      study were to evaluate the clinical characteristics and outcomes of patients who
      were diagnosed with anaphylaxis to fluorescein. The medical records of patients
      with anaphylaxis to intravenous fluorescein angiography (IVFA) admitted to the
      emergency department between January 2010 and June 2012 were retrospectively
      reviewed. Among 12,005 times of IVFA, a total of 10 patients (0.083 %) were
      included in this study. The mean age was 58.3 years, and 50.0 % were men. The
      most common presentation was hypotension (systolic blood pressure <90 mmHg) (70
      %) followed by nausea and vomiting (60 %). Especially, patients with diabetes
      were more prone to develop hypotension and most hypotensive events occurred in
      less than 3 min. All of our patients recovered without sequelae and mortality
      following prompt and proper intervention. Although the incidence is low,
      anaphylaxis due to intravenous fluorescein can occur during IVFA. Physicians
      should be aware of this possible complication, and be prepared to treat it. 

PMID- 24293213
TI  - Target lesions in a neutropenic patient.

PMID- 24293214
TI  - Diagnosing small bowel malabsorption.

PMID- 24293215
TI  - Bone bonding ability of a chemically and thermally treated low elastic modulus Ti
      alloy: gum metal.
AB  - The gum metal with composition Ti-36Nb-2Ta-3Zr-0.3O, is free from cytotoxic
      elements and exhibits a low elastic modulus as well as high mechanical strength.
      We have previously demonstrated that this gum metal, once subjected to a series
      of surface treatments--immersion in 1 M NaOH (alkali treatment) and then 100 mM
      CaCl2, before heating at 700  degrees C (sample: ACaH-GM), with an optional final
      hot water immersion (sample: ACaHW-GM)--has apatite-forming ability in simulated
      body fluid. To confirm the in vivo bioactivity of these treated alloys, failure
      loads between implants and bone at 4, 8, 16, and 26 weeks after implantation in
      rabbits' tibiae were measured for untreated gum metal (UT-GM), ACaH-GM and ACaHW
      GM, as well as pure titanium plates after alkali and heat treatment (AH-Ti). The
      ACaH-GM and UT-GM plates showed almost no bonding, whereas ACaHW-GM and AH-Ti
      plates showed successful bonding by 4 weeks, and their failure loads subsequently
      increased with time. The histological findings showed a large amount of new bone
      in contact with the surface of ACaHW-GM and AH-Ti plates, suggesting that the
      ACaHW treatment could impart bone-bonding bioactivity to a gum metal in vivo.
      Thus, with this improved bioactive treatment, these advantageous gum metals
      become useful candidates for orthopedic and dental devices.

PMID- 24293216
TI  - The estimation of utility weights in cost-utility analysis for mental disorders:
      a systematic review.
AB  - OBJECTIVE: To systematically review approaches and instruments used to derive
      utility weights in cost-utility analyses (CUAs) within the field of mental
      disorders and to identify factors that may have influenced the choice of the
      approach. METHODS: We searched the databases DARE (Database of Abstracts of
      Reviews of Effects), NHS EED (National Health Service Economic Evaluation
      Database), HTA (Health Technology Assessment), and PubMed for CUAs. Studies were
      included if they were full economic evaluations and reported quality-adjusted
      life-years as the health outcome. Study characteristics and instruments used to
      estimate utility weights were described and a logistic regression analysis was
      conducted to identify factors associated with the choice of either the direct
      (e.g. standard gamble) or the preference-based measure (PBM) approach (e.g. EQ
      5D). RESULTS: We identified 227 CUAs with a maximum in 2009, 2010, and 2012. Most
      CUAs were conducted in depression, dementia, or psychosis, and came from the US
      or the UK, with the EQ-5D being the most frequently used instrument. The
      application of the direct approach was significantly associated with depression,
      psychosis, and model-based studies. The PBM approach was more likely to be used
      in recent studies, dementia, Europe, and empirical studies. Utility weights used
      in model-based studies were derived from only a small number of studies.
      LIMITATIONS: We only searched four databases and did not evaluate the quality of
      the included studies. CONCLUSIONS: Direct instruments and PBMs are used to elicit
      utility weights in CUAs with different frequencies regarding study type, mental
      disorder, and country.

PMID- 24293217
TI  - Nonmicrobial-mediated inflammatory airway diseases--an update.
AB  - In lungs, airways are in constant contact with air, microbes, allergens, and
      environmental pollutants. The airway epithelium represents the first line of lung
      defense through different mechanisms, which facilitate clearance of inhaled
      pathogens and environmental particles while minimizing an inflammatory response.
      The innate immune system facilitates immediate recognition of both foreign
      pathogens and tissue damage through toll-like receptor, which acts as a gateway
      for all intracellular events leading to inflammation. In the absence of microbial
      stimulus, the immune system is capable of detecting a wide range of insults
      against the host. This review focuses on various molecular mechanisms involved in
      pathophysiology of airway inflammation mediated by environmental factors,
      cellular stress, and pharmacological and clinical agents. 

PMID- 24293218
TI  - PPARgamma-inactive Delta2-troglitazone independently triggers ER stress and
      apoptosis in breast cancer cells.
AB  - Our aim was to better understand peroxisome proliferator-activated receptor gamma
      (PPARgamma)-independent pathways involved in anti-cancer effects of
      thiazolidinediones (TZDs). We focused on Delta2-troglitazone (Delta2-TGZ), a
      PPARgamma inactive TZD that affects breast cancer cell viability. Appearance of
      TUNEL positive cells, changes in mitochondrial membrane potential, cleavage of
      poly(ADP-ribose) polymerase (PARP)-1 and caspase-7 revealed that apoptosis
      occurred in both hormone-dependent MCF7 and hormone-independent MDA-MB-231 breast
      cancer cells after 24 and 48 h of treatment. A microarray study identified
      endoplasmic reticulum (ER) stress as an essential cellular function since many
      genes involved in ER stress were upregulated in MCF7 cells following Delta2-TGZ
      treatment. Delta2-TGZ-induced ER stress was further confirmed in MCF7 cells by
      phosphorylation of pancreatic endoplasmic reticulum kinase-like endoplasmic
      reticulum kinase (PERK) and its target eIF2alpha after 1.5 h, rapid increase in
      activating transcription factor (ATF) 3 mRNA levels, splicing of X-box binding
      protein 1 (XBP1) after 3 h, accumulation of binding immunogloblulin protein (BiP)
      and CCAAT-enhancer-binding protein homologous protein (CHOP) after 6 h.
      Immunofluorescence microscopy indicated that CHOP was relocalized to the nucleus
      of treated cells. Similarly, in MDA-MB-231 cells, overexpression of ATF3,
      splicing of XBP1, and accumulation of BiP and CHOP were observed following Delta2
      TGZ treatment. In MCF7 cells, knock-down of CHOP or the inhibition of c-Jun N
      terminal kinase (JNK) did not impair cleavage of PARP-1 and caspase-7.
      Altogether, our results show that ER stress is an early response of major types
      of breast cancer cells to Delta2-TGZ, prior to, but not causative of apoptosis.

PMID- 24293219
TI  - Complete genome sequence of Courdo11 virus, a member of the family Mimiviridae.
AB  - Giant viruses of amoebae were discovered 10 years ago and led to the description
      of two new viral families: Mimiviridae and Marseilleviridae. These viruses
      exhibit remarkable features, including large capsids and genomes that are similar
      in size to those of small bacteria and their large genetic repertoires include
      genes that are unique among viruses. The family Mimiviridae has grown during the
      past decade since the discovery of its initial member, Mimivirus, and continues
      to expand. Here, we describe the genome of a new giant virus that infects
      Acanthamoeba spp., Courdo11 virus, isolated in 2010 by inoculating Acanthamoeba
      spp. with freshwater collected from a river in southeastern France. The Courdo11
      virus genome is a double stranded DNA molecule composed of 1,245,674 nucleotides.
      The comparative analyses of Courdo11 virus with the genomes of other giant
      viruses showed that it belongs to lineage C of mimiviruses of amoebae, being most
      closely related to Megavirus chilensis and LBA 111, the first mimivirus isolated
      from a human. Major characteristics of the M. chilensis genome were identified in
      the Courdo11 virus genome, found to encode three more tRNAs. Genomic architecture
      comparisons mirrored previous findings that showed conservation of collinear
      regions in the middle part of the genome and diversity towards the extremities.
      Finally, fourteen ORFans were identified in the Courdo11 virus genome, suggesting
      that the pan-genome of mimiviruses of amoeba might reach a plateau.

PMID- 24293220
TI  - Proteome reference maps of the Lotus japonicus nodule and root.
AB  - Legume symbiosis with rhizobia results in the formation of a specialized organ,
      the root nodule, where atmospheric dinitrogen is reduced to ammonia. In Lotus
      japonicus (Lotus), several genes involved in nodule development or nodule
      function have been defined using biochemistry, genetic approaches, and high
      throughput transcriptomics. We have employed proteomics to further understand
      nodule development. Two developmental stages representing nodules prior to
      nitrogen fixation (white) and mature nitrogen fixing nodules (red) were compared
      with roots. In addition, the proteome of a spontaneous nodule formation mutant
      (snf1) was determined. From nodules and roots, 780 and 790 protein spots from 2D
      gels were identified and approximately 45% of the corresponding unique gene
      accessions were common. Including a previous proteomics set from Lotus pod and
      seed, the common gene accessions were decreased to 7%. Interestingly, an
      indication of more pronounced PTMs in nodules than in roots was determined.
      Between the two nodule developmental stages, higher levels of pathogen-related 10
      proteins, HSPs, and proteins involved in redox processes were found in white
      nodules, suggesting a higher stress level at this developmental stage. In
      contrast, protein spots corresponding to nodulins such as leghemoglobin,
      asparagine synthetase, sucrose synthase, and glutamine synthetase were prevalent
      in red nodules. The distinct biochemical state of nodules was further highlighted
      by the conspicuous presence of several nitrilases, ascorbate metabolic enzymes,
      and putative rhizobial effectors. 

PMID- 24293221
TI  - Retrospective evaluation of the outcomes of children with diffuse intrinsic
      pontine glioma treated with radiochemotherapy and valproic acid in a single
      center.
AB  - Diffuse intrinsic pontine glioma is a pediatric oncologic disease with dismal
      prognosis and no effective treatment. Since 2007, our patients have been using
      valproic acid as prophylactic anticonvulsant. We have undertaken a retrospective
      study in order to evaluate the influence of valproate in the outcomes of children
      with this disease in our center. Patients were treated with weekly carboplatin
      and vincristine and received conformal radiotherapy, either concurrent or
      sequential. Event-free survival and overall survival of patients not treated with
      valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a
      parametric multivariate regression test for time-to-failure data) showed a
      statistically significant superiority of the median event-free survival of
      treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33
      0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated
      patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).

PMID- 24293222
TI  - Development and use of an atomistic CHARMM-based forcefield for peptoid
      simulation.
AB  - Peptoids are positional isomers of peptides: peptoid sidechains are attached to
      backbone nitrogens rather than alpha-carbons. Peptoids constitute a class of
      sequence-specific polymers resistant to biological degradation and potentially as
      diverse, structurally and functionally, as proteins. While molecular simulation
      of proteins is commonplace, relatively few tools are available for peptoid
      simulation. Here, we present a first-generation atomistic forcefield for
      peptoids. Our forcefield is based on the peptide forcefield CHARMM22, with key
      parameters tuned to match both experimental data and quantum mechanical
      calculations for two model peptoids (dimethylacetamide and a sarcosine
      dipeptoid). We used this forcefield to demonstrate that solvation of a dipeptoid
      substantially modifies the conformations it can access. We also simulated a
      crystal structure of a peptoid homotrimer, H-(N-2-phenylethyl glycine)3 -OH, and
      we show that experimentally observed structural and dynamical features of the
      crystal are accurately described by our forcefield. The forcefield presented here
      provides a starting point for future development of peptoid-specific simulation
      methods within CHARMM.

PMID- 24293223
TI  - Participatory data analysis alongside co-researchers who have Down syndrome.
AB  - BACKGROUND: There is comparatively little published research that transparently
      charts the contribution of people with an intellectual disability to a
      collaborative research process. This paper illustrates the process of data
      analysis in a project located within the Emancipatory Disability Research (EDR)
      paradigm. MATERIALS AND METHODS: Textual data was made available from a
      participatory action research project involving young people who have Down
      syndrome. A university based researcher analysed a portion of the data set using
      thematic networks with the participation of co-researchers in iterative cycles of
      reflexivity. RESULTS: The participation of the co-researchers is demonstrated and
      a global theme, deduced from the collaborative analysis, is described.
      CONCLUSION: Authentic participation of co-researchers in the data analysis stage
      of the research process is an example of 'inclusive research' and assures
      adherence to the principles of EDR in informing the theory and practice of social
      inclusion for young adults with an intellectual disability. BACKGROUND: There are
      not many research projects which include people with an intellectual disability
      in data analysis. This paper tells the story of how a small group of people with
      Down syndrome called co-researchers, joined in analysing data from their peers in
      a research project. MATERIALS AND METHODS: The co-researchers worked in a group.
      They took some copies of typed up interviews, underlined words and made notes on
      parts of the interview they found interesting and important. RESULTS: Through
      their work, the co-researchers found that being involved with other people and
      having friends is important but can be hard sometimes. CONCLUSION: This work is
      important as it shows the abilities of some people with Down syndrome in data
      analysis work. The co-researchers were included in research that is about
      themselves and other people with intellectual disabilities.

PMID- 24293224
TI  - Regulatory circuits in cell motility.

PMID- 24293225
TI  - A multi-site controlled trial of the R&R2MHP cognitive skills program for
      mentally disordered female offenders.
AB  - This study aimed to evaluate the acceptability and efficacy of delivering the
      Reasoning and Rehabilitation Mental Health Program (R&R2MHP) to female mentally
      disordered offenders detained in medium and low secure hospital settings. Group
      treatment participants (N = 18) and control participants receiving treatment as
      usual (N = 20) completed self-report measures pre- and post-group. An informant
      measure of ward behavior was also completed by staff. Violent attitudes and locus
      of control were assessed at 3-month follow-up. Program completion was excellent
      (89%). A conservative intention-to-treat analysis found significant treatment
      effects post-group for positive problem-solving orientation, rational problem
      solving style, and locus of control (medium-large effect), but no treatment
      effect for violent attitudes, anger, and ward behavior. At follow-up, a large
      treatment effect was found for locus of control. Ad hoc per protocol analyses
      found a large treatment effect for ward behavior. The findings provide
      preliminary support for the feasibility and utility of delivering R&R2MHP to
      females in secure psychiatric settings. 

PMID- 24293226
TI  - Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot
      (Myiopsitta monachus).
AB  - Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a
      progressive disease characterized by the formation of plaques in the arteries
      accompanied by underlying chronic inflammation. The family of n-3 fatty acids,
      especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n
      3, DHA), have consistently been shown to reduce atherosclerotic risk factors in
      humans and other mammals. Some avian species have been observed to convert alpha
      linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk
      71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore,
      the metabolic effects of including flaxseed oil, as a source of ALA, in the diet
      at three different levels (low, medium, and high) on the lipid metabolism of Monk
      parrots was evaluated through measuring plasma total cholesterol (TC), free
      cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed
      intake, body weight, and body condition score were also assessed. Thus the dose
      and possible saturation response of increasing dietary ALA at constant linoleic
      acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M.
      monachus) was evaluated. Calculated esterified cholesterol in addition to plasma
      TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had
      elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn
      3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid
      20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the
      present data were combined with data from a previous study (Petzinger et al. in J
      Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when
      LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were
      positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Delta7),
      arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with
      dietary en% ALA. 

PMID- 24293228
TI  - 'Sustainable materials management': a new international solid waste paradigm.

PMID- 24293227
TI  - Conjugated linoleic acid (t-10, c-12) reduces fatty acid synthesis de novo, but
      not expression of genes for lipid metabolism in bovine adipose tissue ex vivo.
AB  - We hypothesized that exogenous fatty acids, and especially or 18:2 trans-10, cis
      12 conjugated linoleic acid (CLA), would decrease adipogenic and lipogenic gene
      expression and de novo fatty acid biosynthesis in intramuscular (i.m.) and
      subcutaneous (s.c.) adipose tissues. Fresh i.m. and s.c. adipose tissues were
      collected from the longissimus thoracis muscle of Angus steers at 12, 14, and 16
      months of age (n = 4 per time point). Adipose tissue explants were incubated in
      duplicate for 48 h with 40 MUM alpha-linolenic (ALA), oleic, stearic, trans
      vaccenic, or CLA. Adipocyte size, acetate and glucose incorporation into fatty
      acids in vitro and mRNA levels for C/EBPbeta, CPT1beta, GPR43, PPARgamma, PRKAA1
      (AMPKalpha) and SCD1 were measured following the incubations. PRKAA1 and SCD1gene
      expression were greater (P < 0.001) in s.c. adipose tissue than in i.m. adipose
      tissue and acetate incorporation into lipids and C/EBPbeta, PPARgamma, and
      SCD1gene expression were greater at 16 months of age than at 12 months of age in
      i.m. adipose (P < 0.01). C/EBPbeta gene expression increased by 16 months of age
      and PRKAA1 gene expression decreased by 16 months of age in s.c. adipose tissue.
      All fatty acids increased s.c. adipocyte volumes whereas CLA decreased acetate
      incorporation into lipids in s.c. adipose tissue (P < 0.05), but none of the
      fatty acids affected gene expression in i.m. or s.c. adipose tissue (P > 0.10).
      Thus, CLA depressed de novo fatty acid biosynthesis from acetate but neither CLA
      nor other fatty acids significantly affected adipogenic or lipogenic gene
      expression. 

PMID- 24293229
TI  - A Comparison of deterministic and probabilistic approaches for assessing risks
      from contaminated aquifers: an Italian case study.
AB  - In this article we consider the methods of deterministic and probabilistic risk
      analysis regarding the presence of chemical contaminants in soil, water and air,
      with a broader meaning than usual for the latter, as we extended the
      probabilistic treatment to the parameters that influence the transport to a
      greater extent, in particular hydraulic conductivity and partition coefficient.
      These parameters, to which only one value is assigned, are considered here as
      random variables. The objective of the study reported herein was to demonstrate
      that application of the probabilistic method of risk assessment is preferable to
      the use of the deterministic method. Both methods yield contaminant removal
      levels that will reduce adverse effects on human health and the environment, but
      results from the deterministic method are typically more conservative than
      necessary, and are thus more costly to achieve. In addition, we found it
      essential to consider the importance of random variables (the parameters
      influencing the flow and the transport), such as the hydraulic conductivity and
      the partition coefficient, when assessing health risks. Both methodologies of
      health risk analysis, deterministic and probabilistic, were applied to a site in
      southern Italy, contaminated by heavy metals. The results obtained confirm the
      purposes of this study. 

PMID- 24293230
TI  - Review, mapping and analysis of the agricultural plastic waste generation and
      consolidation in Europe.
AB  - A review of agricultural plastic waste generation and consolidation in Europe is
      presented. A detailed geographical mapping of the agricultural plastic use and
      waste generation in Europe was conducted focusing on areas of high concentration
      of agricultural plastics. Quantitative data and analysis of the agricultural
      plastic waste generation by category, geographical distribution and compositional
      range, and physical characteristics of the agricultural plastic waste per use and
      the temporal distribution of the waste generation are presented. Data were
      collected and cross-checked from a variety of sources, including European,
      national and regional services and organizations, local agronomists, retailers
      and farmers, importers and converters. Missing data were estimated indirectly
      based on the recorded cultivated areas and the characteristics of the
      agricultural plastics commonly used in the particular regions. The temporal
      distribution, the composition and physical characteristics of the agricultural
      plastic waste streams were mapped by category and by application. This study
      represents the first systematic effort to map and analyse agricultural plastic
      waste generation and consolidation in Europe. 

PMID- 24293231
TI  - Household hazardous wastes as a potential source of pollution: a generation
      study.
AB  - Certain domestic wastes exhibit characteristics that render them dangerous, such
      as explosiveness, flammability, spontaneous combustion, reactivity, toxicity and
      corrosiveness. The lack of information about their generation and composition
      hinders the creation of special programs for their collection and treatment,
      making these wastes a potential threat to human health and the environment. We
      attempted to quantify the levels of hazardous household waste (HHW) generated in
      Mexicali, Mexico. The analysis considered three socioeconomic strata and eight
      categories. The sampling was undertaken on a house-by-house basis, and hypothesis
      testing was based on differences between two proportions for each of the eight
      categories. In this study, HHW comprised 3.49% of the total generated waste,
      which exceeded that reported in previous studies in Mexico. The greatest quantity
      of HHW was generated by the middle stratum; in the upper stratum, most packages
      were discarded with their contents remaining. Cleaning products represent 45.86%
      of the HHW generated. Statistical differences were not observed for only two
      categories among the three social strata. The scarcity of studies on HHW
      generation limits direct comparisons. Any decrease in waste generation within the
      middle social stratum will have a large effect on the total amount of waste
      generated, and decrease their impact on environmental and human health. 

PMID- 24293233
TI  - Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO
      (Italian Association of Neuro-Oncology).
AB  - The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in
      recurrent glioblastoma is unknown. We performed a phase 2 trial of combined
      bevacizumab and fotemustine for patients with glioblastoma at first relapse after
      radiotherapy and temozolomide. The primary endpoint was 6-month progression-free
      survival (PFS), while secondary endpoints were overall survival (OS), response
      rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM
      were enrolled. The authors observed a 6-month PFS rate of 42.6% (95% CI 29.3
      55.2) and a median PFS of 5.2 months (95% CI 3.8-6.6). The median OS was 9.1
      months (95% CI 7.3-10.3). Twenty-eight patients (52%) had a radiographic
      response, and a significant neurological improvement with steroid reduction was
      observed in 25/42 symptomatic patients (60%). MGMT promoter methylation was
      significantly associated with improved PFS in univariate analysis. Most unifocal
      tumors at baseline had a focal enhancing progression (76%), while the diffuse non
      enhancing progression accounted for 9.5%. Response or survival were not
      associated with any pattern of progression. Survival after failure of treatment
      was short. Twelve out of 54 patients (22%) discontinued fotemustine for grade 3/4
      myelotoxicity, while 4/54 (7.4%) discontinued bevacizumab. This study failed to
      demonstrate a superiority of the combination of bevacizumab and fotemustine over
      either bevacizumab or fotemustine alone as historical controls. Future studies
      should explore alternative regimens of combination of the two drugs.

PMID- 24293237
TI  - Proteome characterization of splenocytes from an Abetapp/ps-1 Alzheimer's disease
      model.
AB  - Alzheimer's disease (AD) is the sixth leading cause of US deaths. In addition to
      neurodegenerative deficits in AD, changes in the immune system have also been
      observed. Proteomic analysis of specific immune cell populations may help gain
      insights into mechanisms of peripheral immunity in AD. Herein, we report proteome
      characterization for two subsets of splenocytes (i.e. CD90+ cells and a
      heterogeneous pool of CD90- cells) from a double transgenic mutant amyloid
      precursor protein/presenilin-1 (Abetapp/ps-1) AD mouse model. Overall, 906
      proteins were identified from both cell types with 275 and 334 proteins uniquely
      identified as CD90+ and CD90- cells, respectively. Proteins identified in CD90+
      and CD90- cells were significantly involved in 18 and 19 KEGG pathways,
      respectively. Amongst these, pathways associated with AD and antigen processing
      and presentation were identified in CD90+ and CD90- subsets, respectively. This
      is the first study to provide a reference proteome map for splenocyte populations
      in Abetapp/ps-1 double transgenic mice which will be helpful for future studies
      focused on understanding peripheral changes in this model. All MS data have been
      deposited in the ProteomeXchange with identifier PXD000203
      (http://proteomecentral.proteomexchange.org/dataset/PXD000203). 

PMID- 24293234
TI  - Withaferin A inhibits experimental epithelial-mesenchymal transition in MCF-10A
      cells and suppresses vimentin protein level in vivo in breast tumors.
AB  - We have shown previously that withaferin A (WA), a bioactive component of the
      medicinal plant Withania somnifera, inhibits growth of cultured and xenografted
      human breast cancer cells and prevents breast cancer development and pulmonary
      metastasis incidence in a transgenic mouse model. The present study was
      undertaken to determine if the anticancer effect of WA involved inhibition of
      epithelial-mesenchymal transition (EMT). Experimental EMT induced by exposure of
      MCF-10A cells to tumor necrosis factor-alpha (TNF-alpha) and transforming growth
      factor-beta1 (TGF-beta) was partially reversed by treatment with WA but not by
      its structural analogs withanone or withanolide A. Combined TNF-alpha and TGF
      beta treatments conferred partial protection against MCF-10A cell migration
      inhibition by WA. Inhibition of TNF-alpha and TGF-beta-induced MCF-10A cell
      migration by WA exposure was modestly attenuated by knockdown of E-cadherin
      protein. MCF-7 and MDA-MB-231 cells exposed to WA exhibited sustained (MCF-7) or
      transient (MDA-MB-231) induction of E-cadherin protein. On the other hand, the
      level of vimentin protein was increased markedly after 24 h treatment of MDA-MB
      231 cells with WA. WA-induced apoptosis was not affected by vimentin protein
      knockdown in MDA-MB-231 cells. Protein level of vimentin was significantly lower
      in the MDA-MB-231 xenografts as well as in MMTV-neu tumors from WA-treated mice
      compared with controls. The major conclusions of the present study are that (a)
      WA treatment inhibits experimental EMT in MCF-10A cells, and (b) mammary cancer
      growth inhibition by WA administration is associated with suppression of vimentin
      protein expression in vivo.

PMID- 24293238
TI  - In vitro biocompatibility evaluations of hyperbranched polyglycerol hybrid
      nanostructure as a candidate for nanomedicine applications.
AB  - In the present study, a detailed biocompatibility testing of a novel class of
      hybrid nanostructure based on hyperbranched polyglycerol and beta-cyclodextrin is
      conducted. This highly water soluble nanostructure with size of less than 10 nm,
      polydispersity of less than 1.3, chemical tenability and highly branched
      architecture with the control over branching structure could be potentially used
      as a carrier in drug delivery systems. To this end, extensive studies in vitro
      and in vivo conditions have to be demonstrated. The in vitro studies include in
      vitro cytotoxicity tests; MTT and Neutral Red assay as an indicator of
      mitochondrial and lysosomal function, and blood biocompatibility tests such as
      effects on coagulation cascade, and complement activation. The results show that
      these hybrid nanostructures, which can be prepared in a simple reaction, are
      considerably biocompatible. The in vivo studies showed that the hybrid
      nanostructure is well tolerated by rats even in high doses of 10 mg ml(-1). After
      autopsy, the normal structure of liver tissue was observed; which divulges high
      biocompatibility and their potential applications as drug delivery and
      nanomedicine. 

PMID- 24293240
TI  - A combined semiempirical and DFT computational protocol for studying
      bioorganometallic complexes: application to molybdocene-cysteine complexes.
AB  - Computational methods can help in the design of new bioorganometallic compounds.
      However, the presence of multihapto or sigma/pi metal-ligand bonding still
      precludes the direct application of either pure molecular mechanics (MM) or
      hybrid quantum mechanics-MM methods to study the flexibility of biomolecules in
      complex with organometallics. Herein, we present a computational protocol aimed
      to the evaluation of the relative free energies of bioorganometallic compounds,
      which explores the conformational space by means of Molecular Dynamics
      simulations using the semiempirical PM6 method coupled with the COnductor-like
      Screening MOdel solvation model followed by density functional theory (DFT)
      calculations including the DFT-D3 dispersion energy correction on the most stable
      conformers. This protocol is applied to investigate the complexes formed between
      cysteine and the molybdocene entity Cp2Mo(2+) (Cp=eta(5)-C5H5), which has
      received considerable attention due to its potential antitumor activity and
      chemical reactivity. The calculated structures and free energies are in agreement
      with those of the experimentally detected molybdocene-cysteine adducts and allow
      us to investigate the reaction mechanism for the formation of the most stable 1:1
      and 1:2 adducts.

PMID- 24293239
TI  - Nitric oxide-eluting nanocomposite for cardiovascular implants.
AB  - Cardiovascular implants must resist thrombosis and intimal hyperplasia, but they
      are prone to such patency limiting conditions during graft implantation and prior
      to endothelialisation. Nitric oxide (NO) released from the endothelium has a
      complex protective role in the cardiovascular system, and this study has
      addressed: (1) in situ NO release profiles from S-nitrosothiols ((S-Nitroso-N
      acetylpenicillamine (SNAP) and (S-Nitrosoglutathione (GSNO)) incorporated into
      polyhedral oligomeric silsesquioxanepoly(carbonate-urea)urethane (POSS-PCU)
      coronary artery bypass grafts (CABG) in a physiological pulsatile flow, and (2)
      the determination of their interaction with endothelial progenitor cells (EPCs),
      smooth muscle cells, platelets, whole blood kinetics. It was found that 1, 2, and
      3 wt% SNAP/GSNO incorporated into POSS-PCU-CABG successfully eluted NO, but
      optimal elution was evident with 2 %-SNAP-POSS-PCU. NO release determined under
      static conditions using the Griess assay, and in situ measurements under
      pulsatile flow using amperometric probe was found to differ, thus confirming the
      significance of monitoring NO-elution under haemodynamic conditions. 2 %-SNAP
      POSS-PCU demonstrated anti-thrombogenic kinetics through thromboelastography
      measurements, while metabolic activity using Alamar BlueTM assay and scanning
      electron microscopy demonstrated greater adhesion of EPCs and reduced adhesion of
      platelets. 

PMID- 24293241
TI  - Development of an indirect sandwich ELISA for detection of urinary antigen, using
      Legionella pneumophila PAL protein.
AB  - Legionella pneumophila peptidoglycan-associated lipoprotein (PAL) protein is an
      extremely conserved antigen among Legionella species. In this study, rabbit and
      rat anti-PAL immunoglobulin G antibodies were produced by immunization with
      purified, recombinant PAL (r-PAL) protein of L. pneumophila serogroup 1 and used
      as capture and detection antibodies in the PAL antigen-based enzyme-linked
      immunosorbent assay (ELISA) to detect urinary PAL antigen. Urine samples were
      obtained from rats experimentally infected with L. pneumophila serogroup 1. The
      PAL antigen was measured in urine samples of 40 infected and 40 uninfected rats.
      After choosing the cut-off value of 0.192, the sensitivity and specificity of the
      PAL antigen-based ELISA were 87.5 and 97.5 %, respectively. The results obtained
      by PAL antigen base ELISA were compared with those obtained by Biotest. The PAL
      antigen was detected efficiently by both of the assays and all of the control
      human urine samples were negative by the ELISA test. The PAL antigen-based ELISA
      assay was relatively simple to perform, precise, highly sensitive and specific,
      and reproducible. Based on our data the PAL antigen-based ELISA described here is
      the first indirect sandwich ELISA for urinary antigen detection which could
      easily be applied for diagnosis of Legionnaires disease.

PMID- 24293242
TI  - Clinical evaluation of mtp40 polymerase chain reaction for the diagnosis of extra
      pulmonary tuberculosis.
AB  - Rapid and sensitive detection of Mycobacterium tuberculosis from patient samples
      is vital for clinical diagnosis and treatment. The emergence of M. tuberculosis
      strains with either no copies or only a single copy of IS6110 in Asian countries
      makes the standard PCR based diagnosis of M. tuberculosis using IS6110 not
      reliable. We studied the diagnostic efficacy of the in-house PCR amplification of
      the candidate gene mtp40 as an alternative to IS6110 element based diagnosis.
      Clinical samples included pulmonary and extra-pulmonary specimens from TB
      suspected patients residing in Puducherry, South India and were analyzed using in
      house PCR procedures targeting IS6110 element and mtp40 genes. Out of 317
      clinical specimens analyzed, 132 (41.6 %) and 114 (36 %) were found positive for
      mtp40 PCR and IS6110 PCR, respectively. However, 18 specimens that were found to
      negative for IS6110 PCR were found positive for mtp40 PCR, which was further
      confirmed by DNA sequencing method. PCR amplification of mtp40 gene for the
      diagnosis of M. tuberculosis in clinical samples is fast, sensitive, and further
      identified clinical strains that lack IS6110 element in this region. It is
      clearly demonstrated that there is a significant difference between the two PCR
      procedures and the sensitivity and specificity levels of mtp40 PCR were found to
      be higher when compared with DNA sequencing method. Thus, mtp40 based PCR
      technique will be beneficial in diagnosis of TB where M. tuberculosis strains
      lack of IS6110 element is predominant. 

PMID- 24293243
TI  - Characterization of cis-acting elements residing in the chitinase promoter of
      Bacillus pumilus SG2.
AB  - Bacillus pumilus SG2 is a chitinolytic bacterium that produces two chitinases,
      namely ChiS and ChiL. The chiS and chiL genes are consecutively expressed under a
      common promoter. Regulation of the chiS and chiL genes is under the control of
      carbon catabolite repression (CCR) in B. pumilus. This study aimed to investigate
      the cis-acting elements of the chitinase promoter. For this purpose, we
      transferred the chiS gene along with its specific promoter to Bacillus subtilis
      as a host. Primer extension analysis revealed two transcription start sites
      located 287 and 65 bp upstream of the chiS start codon. The distal promoter was
      highly compatible with the consensus sequence of the sigma(A)-type promoters in
      B. subtilis, whereas the proximal promoter sequence showed less similarity to the
      sigma(A)-type consensus sequence. A catabolite responsive element (cre), which is
      required for CCR in Bacillus species, was found to be 136 to 123 bp upstream of
      the chiS start codon. Interestingly, this cre site was located upstream of the 
      35 of the proximal promoter and downstream of the distal promoter. Deletion of
      this cre site sequence rendered the chiS expression constitutive.

PMID- 24293244
TI  - Tests examining skill outcomes in sport: a systematic review of measurement
      properties and feasibility.
AB  - BACKGROUND: A high level of participant skill is influential in determining the
      outcome of many sports. Thus, tests assessing skill outcomes in sport are
      commonly used by coaches and researchers to estimate an athlete's ability level,
      to evaluate the effectiveness of interventions or for the purpose of talent
      identification. OBJECTIVE: The objective of this systematic review was to examine
      the methodological quality, measurement properties and feasibility
      characteristics of sporting skill outcome tests reported in the peer-reviewed
      literature. DATA SOURCES: A search of both SPORTDiscus and MEDLINE databases was
      undertaken. STUDY SELECTION: Studies that examined tests of sporting skill
      outcomes were reviewed. Only studies that investigated measurement properties of
      the test (reliability or validity) were included. A total of 22 studies met the
      inclusion/exclusion criteria. STUDY APPRAISAL AND SYNTHESIS METHODS: A customised
      checklist of assessment criteria, based on previous research, was utilised for
      the purpose of this review. RESULTS: A range of sports were the subject of the 22
      studies included in this review, with considerations relating to methodological
      quality being generally well addressed by authors. A range of methods and
      statistical procedures were used by researchers to determine the measurement
      properties of their skill outcome tests. The majority (95%) of the reviewed
      studies investigated test-retest reliability, and where relevant, inter and intra
      rater reliability was also determined. Content validity was examined in 68% of
      the studies, with most tests investigating multiple skill domains relevant to the
      sport. Only 18% of studies assessed all three reviewed forms of validity
      (content, construct and criterion), with just 14% investigating the predictive
      validity of the test. Test responsiveness was reported in only 9% of studies,
      whilst feasibility received varying levels of attention. LIMITATIONS: In
      organised sport, further tests may exist which have not been investigated in this
      review. This could be due to such tests firstly not being published in the peer
      review literature and secondly, not having their measurement properties (i.e.,
      reliability or validity) examined formally. CONCLUSIONS: Of the 22 studies
      included in this review, items relating to test methodological quality were, on
      the whole, well addressed. Test-retest reliability was determined in all but one
      of the reviewed studies, whilst most studies investigated at least two aspects of
      validity (i.e., content, construct or criterion-related validity). Few studies
      examined predictive validity or responsiveness. While feasibility was addressed
      in over half of the studies, practicality and test limitations were rarely
      addressed. Consideration of study quality, measurement properties and feasibility
      components assessed in this review can assist future researchers when developing
      or modifying tests of sporting skill outcomes.

PMID- 24293245
TI  - Nonmicrosurgical options for soft tissue reconstruction of the hand.
AB  - There are many options for nonmicrosurgical soft tissue coverage of hand wounds,
      ranging from split thickness skin grafting to pedicled soft tissue transfer,
      depending on the size, location, blood supply, and depth of the wound. Although
      many of these techniques have been available for decades, recent advancements in
      wound management include synthetic dermal substitution, new dressing materials,
      and variations on previously described or novel pedicled flaps.The goals of
      coverage include maximizing healing, function, aesthetic appearance, and patient
      satisfaction, while minimizing donor site morbidity. Optimal management often
      relies on an individual surgeon's assessment and judgment, as hand wounds can
      vary greatly and pose unique challenges, and multiple coverage options often
      exist for each wound. Here, we aim to present useful and up-to-date information
      on nonmicrosurgical soft tissue coverage for hand reconstruction focusing on
      recent findings of interest to provide an update on areas with evolving evidence.

PMID- 24293246
TI  - Towards area-wide control of Bactrocera invadens: prospects of the sterile insect
      technique and molecular entomology.
AB  - It is 10 years since the first detection of the invader fruit fly, Bactrocera
      invadens, in sub-Saharan Africa. The pest continues to hamper fruit production
      and create barriers to trade. Strategies currently employed to control B.
      invadens are insufficient, and more effective area-wide strategies are needed.
      The sterile insect technique and molecular entomology approaches have high
      potential and could help to bring about effective area-wide control of the pest
      if adopted and used as components of area-wide integrated pest management.

PMID- 24293247
TI  - A cure with successful staged treatment of aortoesophageal fistula.
AB  - Aortoesophageal fistula is a fatal disease which needs immediate control of
      bleeding and infection. We report a case of aortoesophageal fistula successfully
      treated with extra-anatomical bypass and complete resection of infected aorta and
      esophagus following endovascular repair. He was discharged after reconstruction
      of esophagus and recurrence of infection has not been observed for the past 5
      years.

PMID- 24293248
TI  - Bioactive nanocomposite for chest-wall replacement: Cellular response in a murine
      model.
AB  - Chest-wall invading malignancies usually necessitate the resection of the
      respective part of the thoracic wall. Gore-Tex(r) is the material of choice that
      is traditionally used to repair thoracic defects. This material is well accepted
      by the recipient; however, though not rejected, it is an inert material and
      behaves like a 'foreign body' within the thoracic wall. By contrast, there are
      materials that have the potential to physiologically integrate into the host, and
      these materials are currently under in vitro and also in vivo investigation.
      These materials offer a gradual but complete biodegradation over time, and severe
      adverse inflammatory responses can be avoided. Here, we present a novel material
      that is a biodegradable nanocomposite based on poly-lactic-co-glycolic acid and
      amorphous calcium phosphate nanoparticles in comparison to the traditionally
      employed Gore-Tex(r) being the standard for chest-wall replacement. On a mouse
      model of thoracic wall resection, that resembles the technique and localization
      applied in humans, poly-lactic-co-glycolic acid and amorphous calcium phosphate
      nanoparticles and Gore-Tex(r) were implanted subcutaneously and additionally
      tested in a separate series as a chest-wall graft. After 1, 2, 4 and 8 weeks cell
      infiltration into the respective materials, inflammatory reactions as well as neo
      vascularization (endothelial cells) were determined in six different zones. While
      Gore-Tex(r) allowed for cell infiltration only at the outer surface, electrospun
      poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles were
      completely penetrated by infiltrating cells. These cells were composed mainly by
      macrophages, with only 4% of giant cells and lymphocytes. Total macrophage count
      increased by time while the number of IL1-beta-expressing macrophages decreased,
      indicating a protective state towards the graft. As such, poly-lactic-co-glycolic
      acid and amorphous calcium phosphate nanoparticles seem to develop ideal
      characteristics as a material for chest-wall replacement by (a) having the
      advantage of full biodegradation, (b) displaying stable chest-wall structures and
      (c) adapting a physiological and integrating graft compared to Gore-Tex(r).

PMID- 24293249
TI  - Tat-DJ-1 protects neurons from ischemic damage in the ventral horn of rabbit
      spinal cord via increasing antioxidant levels.
AB  - The DJ-1 gene is highly conserved in diverse species and DJ-1 is known as an anti
      oxidative stress factor. In this study, we investigated the neuroprotective
      effects of DJ-1 against ischemic damage in the rabbit spinal cord. Tat-DJ-1
      fusion proteins were constructed to facilitate the penetration of DJ-1 protein
      into the neurons. Tat-1-DJ-1 fusion protein was administered to the rabbit 30 min
      after ischemia/reperfusion, and transient spinal cord ischemia was induced by
      occlusion of the aorta at the subrenal region for 15 min. The administration of
      Tat-DJ-1 significantly improved the Tarlov score compared to that in the Tat
      (vehicle)-treated group at 24, 48 and 72 h after ischemia/reperfusion. At 72 h
      after ischemia/reperfusion, the number of cresyl violet-positive neurons was
      significantly increased in the Tat-DJ-1-treated group compared to that in the
      vehicle-treated group. Lipid peroxidation as judged from the malondialdehyde
      levels was significantly decreased in the Tat-DJ-1-treated group compared to that
      in the vehicle-treated group. In contrast, superoxide dismutase and catalase
      levels were significantly increased in the Tat-DJ-1-treated group compared to
      that in the vehicle-treated group. This result suggests that DJ-1 protects
      neurons from ischemic damage in the ventral horn of the spinal cord via its
      antioxidant effects.

PMID- 24293251
TI  - Conserved genes, sampling error, and phylogenomic inference.

PMID- 24293250
TI  - Nanomedicine: action of metal nanoparticles on neuronal nitric oxide synthase
      fluorimetric analysis on the mechanism for fibrillogenesis.
AB  - The incubation of neuronal nitric oxide synthase with the five amyloid peptide
      fragments [Abeta17-21; Abeta25-29; Abeta29-33; Abeta33-37; Abeta25-37] catalyzed
      the formation of fibrils. The role of neuronal isomer (nNOS) involved the
      entrapment of free monomers and seed aggregates to initiate the events of
      nucleation and elongation, critical for the formation of fibrils. It was evident
      that the hydrophobic nature of Abeta17-21, the three glycine zipper peptides
      [Abeta25-29; Abeta29-33; Abeta33-37] and Abeta25-37 was a trigger in the
      formation of fibrils and was a force critical in the association of the peptides
      with the enzyme. Gold and silver nanoparticles (average 4.0 nm) inhibited fibril
      formation when added to the induced fibrils from nNOS-Abeta incubation. The
      addition of nNOS and/or Abeta to co-incubated solutions of nanoparticle-Abeta or
      nanoparticle-nNOS respectively did not prevent fibril formation but reversed it.
      Three mechanisms for this reversal were proposed: (1) depletion of free Abeta
      monomer in solution and blocking potential aggregation sites on the nNOS molecule
      due to large surface area of the nanoparticle (2) hydrophobic interaction between
      the Abeta peptide and nanoparticle (3) disruption of binary adducts between Abeta
      peptides and nNOS by nanoparticles.

PMID- 24293252
TI  - Two-dimensional gel electrophoresis of gastric tissue in an alkaline pH range.
AB  - 2DE in combination with MS has facilitated the discovery of several proteins with
      altered abundance in gastric cancer. While acidic and wide pH ranges have been
      widely investigated, analysis in the alkaline pH range has not been specifically
      performed in gastric cancer to date. In the present study, we initially optimized
      the 2DE in alkaline pH range (pH 7-11) for gastric tissue samples. Using a
      modified lysis buffer, we analyzed pooled nontumor and tumor samples for proteins
      with altered abundance in gastric adenocarcinoma. We successfully identified 38
      silver-stained spots as 24 different proteins. Four of these were chosen for
      investigation with immunoblotting on individual paired samples to determine
      whether the changes seen in 2DE represent the overall abundance of the protein or
      possibly only a single form. While mitochondrial trifunctional protein (MTP)
      subunits were decreased in 2DE gels, immunoblotting identified their overall
      abundance as being differently dysregulated: in the gastric tumor samples, the
      MTP-alpha subunit was decreased, and the MTP-beta subunit was increased. On the
      other hand, heterogenous nuclear ribonucleoprotein M and galectin-4 were
      increased in the gastric tumor samples in both 2DE and immunoblotting. 

PMID- 24293253
TI  - Phenotypic impact of deregulated expression of class I histone deacetylases in
      urothelial cell carcinoma of the bladder.
AB  - Deregulated expression of histone deacetylases (HDACs) has been implicated in
      tumorigenesis. Herein, we investigated class I HDACs expression in bladder
      urothelial cell carcinoma (BUCC), its prognostic value and biological
      significance. Significantly increased transcript levels of all HDACs were found
      in BUCC compared to 20 normal mucosas, and these were higher in lower grade and
      stage tumors. Increased HDAC3 levels were associated with improved patient
      survival. SiRNA experiments showed decrease cell viability and motility, and
      increased apoptosis. We concluded that class I HDACs play an important role in
      bladder carcinogenesis through deregulation of proliferation, migration and
      apoptosis, constituting putative therapeutic targets.

PMID- 24293255
TI  - Preparation of triacylglycerols rich in omega-3 fatty acids from sardine oil
      using a Rhizomucor miehei lipase: focus in the EPA/DHA ratio.
AB  - The increasing evidence on the differential biochemical effects of
      eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) raises the need of n-3
      highly unsaturated fatty acid concentrates with different amounts of these fatty
      acids. In the present work, physicochemical and enzymatic techniques were
      combined to obtain acylglycerols, mainly triacylglycerols (TAG), rich in n-3
      fatty acids. Sardine oil was obtained by washing sardine (Sardina pilchardus)
      mince with a NaHCO3 solution, hydrolyzed in a KOH-ethanol solution, and
      concentrated with urea. The esterification reaction was performed in the
      stoichiometric proportion of substrates for re-esterification to TAG, with 10 %
      level of Rhizomucor miehei lipase based on the weight of substrates, without any
      solvent, during 48 h. This procedure led to approximately 88 % of acylglycerols,
      where more than 66 % were TAG and the concentration of n-3 fatty acids was higher
      than 60 %, the EPA and DHA ratio (EPA/DHA) was 4:1. The content of DHA in the
      unesterifed fraction (free fatty acids) increased from 20 to 54 %, while the EPA
      level in the same fraction decreased from 33 to 12.5 % (EPA/DHA ratio ~1:4).
      Computational methods (density functional theory calculations) have been carried
      out at the B3LYP/6-31G(d,p) level to explain some of the experimental results.

PMID- 24293256
TI  - Artificial enzyme mimics for catalysis and double natural enzyme co
      immobilization.
AB  - This work presents a new chemiluminescent (CL) probe array assay. The new type CL
      probe array is based on enzyme mimics of Co3O4-SiO2 mesoporous nanocomposite
      material, which not only have an excellent catalytic effect on the luminol-H2O2
      CL reaction in an alkaline medium but also can be used for the immobilization of
      enzymes. The linear range of the lactose concentration is 3.0 * 10(-7) to 1.0 *
      10(-5) g mL(-1) and the detection limit is 6.9 * 10(-8) g mL(-1). beta
      Galactosidase and glucose oxidase were selected as a model for enzyme assays to
      demonstrate the applicability of Co3O4-SiO2 mesoporous nanocomposite material in
      multienzyme immobilization. The novel bifunctional CL probe array has been
      successfully applied to the determination of lactose in milk.

PMID- 24293254
TI  - Next-generation sequencing to dissect hereditary nephrotic syndrome in mice
      identifies a hypomorphic mutation in Lamb2 and models Pierson's syndrome.
AB  - The study of mutations causing the steroid-resistant nephrotic syndrome in
      children has greatly advanced our understanding of the kidney filtration barrier.
      In particular, these genetic variants have illuminated the roles of the podocyte,
      glomerular basement membrane and endothelial cell in glomerular filtration.
      However, in a significant number of familial and early onset cases, an underlying
      mutation cannot be identified, indicating that there are likely to be multiple
      unknown genes with roles in glomerular permeability. We now show how the
      combination of N-ethyl-N-nitrosourea mutagenesis and next-generation sequencing
      could be used to identify the range of mutations affecting these pathways. Using
      this approach, we isolated a novel mouse strain with a viable nephrotic phenotype
      and used whole-genome sequencing to isolate a causative hypomorphic mutation in
      Lamb2. This discovery generated a model for one part of the spectrum of human
      Pierson's syndrome and provides a powerful proof of principle for accelerating
      gene discovery and improving our understanding of inherited forms of renal
      disease.

PMID- 24293257
TI  - Solution structure of a putative FKBP-type peptidyl-propyl cis-trans isomerase
      from Giardia lamblia.

PMID- 24293258
TI  - Chronic myeloid leukemia patient with co-occurrence of BCR-ABL junction and JAK2
      V617F mutation.
AB  - The JAK2 V617F mutation is common in patients with Philadelphia-negative chronic
      myeloproliferative neoplasms, but few cases of the JAK2 V617F mutation have been
      described in Philadelphia-positive chronic myeloid leukemia (CML) patients. Here,
      we report a 21-year-old female who presented with phenotype of CML in whom BCR
      ABL transcript and JAK2V617F mutation co-occurred. These findings were determined
      through cytogenetic analysis, fluorescence in situ hybridization, and allele
      specific (AS) PCR. The patient's BCR-ABL transcript disappeared after 6 months of
      treatment with imatinib, while the JAK2V617F mutation remained positive. We
      discuss this case with reference to the current literature. 

PMID- 24293259
TI  - The crystal structure of LidA, a translocated substrate of the Legionella
      pneumophila type IV secretion system.

PMID- 24293260
TI  - Light-induced protein translocation by genetically encoded unnatural amino acid
      in Caenorhabditis elegans.

PMID- 24293261
TI  - Gastrodin ameliorates depressive-like behaviors and up-regulates the expression
      of BDNF in the hippocampus and hippocampal-derived astrocyte of rats.
AB  - Gastrodin (GAS), a main constituent of a Chinese herbal medicine Tian ma, has
      been shown to be effective in treating various mood disorders. The purpose of the
      present study was to assess the effects of GAS on alleviating depressive-like
      behaviors in a rat model of chronic unpredictable stress (CUS) and regulating the
      expression of BDNF in the hippocampus and hippocampal-derived astrocyte from
      Sprague-Dawley (SD) rats. Following CUS, rats were intraperitoneally administered
      gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Rats were then
      experienced sucrose preference test and forced swim test. The expressions of GFAP
      and BDNF in the hippocampus were evaluated. In addition, hippocampal astrocytes
      were isolated from neonatal SD rats and exposed to different concentrations of
      GAS (sham, 5, 10, 20, 50 and 100 MUg/mL) for 48 and 72 h before the cell
      viability and the levels of pERK1/2 and BDNF were analyzed. Furthermore, the cell
      viability was also tested after exposure to serum-free condition that contain
      different concentrations of GAS for 48 and 72 h. GAS administration (100 and 200
      mg/kg daily) reversed depressive-like behaviors in rats exposed to CUS paradigm
      and restored the expression of GFAP and BDNF in the hippocampus. Moreover, in
      vitro experiments revealed that GAS did not increase the cell viability of
      astrocytes but protected it from 72 h's serum-free damage at the dosage 20
      MUg/mL. Increased levels of ERK1/2 phosphorylation and BDNF protein were also
      observed after GAS (20 MUg/mL) treatment for 72 h. These results indicate that
      gastrodin possesses antidepressant effect. The changes of the astrocyte
      activation and the level of BDNF may play a critical role in the pharmacological
      action of GAS.

PMID- 24293262
TI  - Delousing efficiency of farmed ballan wrasse (Labrus bergylta) against
      Lepeophtheirus salmonis infecting Atlantic salmon (Salmo salar) post-smolts.
AB  - BACKGROUND: Cleaner-fish (wrasse, Labridae) are increasingly deployed within the
      Atlantic salmon (Salmo salar L.) industry as a biological control against sea
      lice (Lepeophtheirus salmonis Kroyer). Two tank-based trials were performed to
      test the effect of farmed ballan wrasse (Labrus bergylta Ascanius) body mass and
      supplementary feeding on the delousing of Atlantic salmon post-smolts with an
      initial infection level of ~12 lice salmon(-1) and a ~5% wrasse:salmon ratio.
      RESULTS: Sea-louse levels below 0.5 lice salmon(-1) were obtained within 84 h,
      and preferential preying upon larger motile stages was found. The wrasse body
      mass and the availability of fresh, opened blue mussels (Mytilus edulis L.) did
      not significantly affect delousing efficiency. The functional predator response
      was linear, showing no minimum prey density threshold for sea-louse foraging and
      no satiation plateau, in spite of the high consumption rates measured. Sea-louse
      infection levels declined following a one-phase exponential decay model, with a
      standardised decline time constant of 0.8-1.3% h(-1) for each wrasse stocked per
      100 salmon. CONCLUSIONS: Farmed ballan wrasse are confirmed as highly effective
      therapeutic and preventive biological controls against sea-lice. The study
      supports the current minimum hatchery size target (10 mm total length) and the
      use of supplementary feeding to sustain the wrasse stocks in operation. The
      functional predator response and the standardised decline time constant of sea
      louse abundance are proposed as useful indicators of delousing efficiency.

PMID- 24293263
TI  - Doppler evaluation of the posterior cerebral artery in normally grown and growth
      restricted fetuses.
AB  - OBJECTIVE: To evaluate Doppler parameters of the two segments of the posterior
      cerebral artery (PCA) in normally grown and growth restricted (IUGR) fetuses.
      METHODS: Normal reference values of the pulsatility index (PI), peak systolic
      velocity, end-diastolic velocity, and time-averaged maximum velocity from the two
      segments of the PCA (segment one, PCA-S1; segment two, PCA-S2) were constructed
      in 350 pregnant women from 20 to 40 weeks of gestation. The association of the
      two PCA segments with the middle cerebral artery (MCA), and with the umbilical
      artery was evaluated in 50 IUGR fetuses. RESULTS: In normal fetuses, Doppler
      parameters from PCA-S1 and PCA-S2 showed similar behavior throughout gestation.
      In IUGR fetuses, the PI of the two PCA segments was significantly reduced with no
      differences between them. PCA-S2 PI showed a higher correlation with the MCA-PI
      (r = 0.73) than PCA-S1 PI (r = 0.63; p = 0.001). IUGR fetuses showed
      vasodilatation in the PCA earlier than in the MCA disregarding the umbilical
      artery-PI value. CONCLUSION: In IUGR fetuses, the two segments of the PCA show
      signs of vasodilatation earlier than the MCA. As IUGR fetuses deteriorate, the
      two segments of the PCA and the MCA behave similarly.

PMID- 24293264
TI  - Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming
      hypothesis of cancer?
AB  - This article as designed to examine whether the "stoichiometric" or "elite
      models" of the origin of the "induced pluripotent stem" (iPS) cells fits some
      experiment facts from the developmental biology of adult stem cells and from the
      field of cancer research. In brief, since the evidence presented to support the
      stoichiometric model failed to recognize the factual existence of adult organ
      specific stem cells, the model has not been rigorously tested. In addition, the
      demonstration of a subset of cells (MUSE cells) in normal primary in vitro
      cultures of human fibroblasts (the usual source of iPS cells) seems to be the
      origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem
      cell" versus "de-differentiation" or "reprogramming" hypotheses were examined.
      Again, using the role of glycolysis, known to be associated with the Warburg
      effect in cancer cells, a list of experiments showing that (a) normal stem cells,
      which have few mitochondria, metabolize via glycolysis; (b) the stem cells are
      targets for "initiation" or "immortalization" or the blockage of differentiation
      and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate
      dehydrogenase A (LDHA), when expressed, is associated with glycolysis and
      therefore, must be expressed in normal adult stem cells, as well as in cancer
      cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen,
      is associated with the reduction of mitochondrial function and mass and is
      associated with the Warburg effect. Together, these observations from the iPS and
      "cancer stem cell" fields support the idea that both iPS cells and cancer stem
      cell are derived from adult organ-specific stem cells that do not restore or
      switch their metabolism of glucose from oxidative metabolism to glycolysis but,
      rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is
      prevented from differentiation or from metabolizing by oxidative phosphorylation.

PMID- 24293265
TI  - Inability to empathize: brain lesions that disrupt sharing and understanding
      another's emotions.
AB  - Emotional empathy--the ability to recognize, share in, and make inferences about
      another person's emotional state--is critical for all social interactions. The
      neural mechanisms underlying emotional empathy have been widely studied with
      functional imaging of healthy participants. However, functional imaging studies
      reveal correlations between areas of activation and performance of a task, so
      that they can only reveal areas engaged in a task, rather than areas of the brain
      that are critical for the task. Lesion studies complement functional imaging, to
      identify areas necessary for a task. Impairments in emotional empathy have been
      mostly studied in neurological diseases with fairly diffuse injury, such as
      traumatic brain injury, autism and dementia. The classic 'focal lesion' is
      stroke. There have been scattered studies of patients with impaired empathy after
      stroke and other focal injury, but these studies have included small numbers of
      patients. This review will bring together data from these studies, to complement
      evidence from functional imaging. Here I review how focal lesions affect
      emotional empathy. I will show how lesion studies contribute to the understanding
      of the cognitive and neural mechanisms underlying emotional empathy, and how they
      contribute to the management of patients with impaired emotional empathy.

PMID- 24293266
TI  - The medial frontal-prefrontal network for altered awareness and control of action
      in corticobasal syndrome.
AB  - The volitional impairments of alien limb and apraxia are a defining feature of
      the corticobasal syndrome, but a limited understanding of their neurocognitive
      aetiology has hampered progress towards effective treatments. Here we combined
      several key methods to investigate the mechanism of impairments in voluntary
      action in corticobasal syndrome. We used a quantitative measure of awareness of
      action that is based on well-defined processes of motor control; structural and
      functional anatomical information; and evaluation against the clinical volitional
      disorders of corticobasal syndrome. In patients and healthy adults we measured
      'intentional binding', the perceived temporal attraction between voluntary
      actions and their sensory effects. Patients showed increased binding of the
      perceived time of actions towards their effects. This increase correlated with
      the severity of alien limb and apraxia, which we suggest share a core deficit in
      motor control processes, through reduced precision in voluntary action signals.
      Structural neuroimaging analyses showed the behavioural variability in patients
      was related to changes in grey matter volume in pre-supplementary motor area, and
      changes in its underlying white matter tracts to prefrontal cortex. Moreover,
      changes in functional connectivity at rest between the pre-supplementary motor
      area and prefrontal cortex were proportional to changes in binding. These
      behavioural, structural and functional results converge to reveal the frontal
      network for altered awareness and control of voluntary action in corticobasal
      syndrome, and provide candidate markers to evaluate new therapies. 

PMID- 24293268
TI  - Making Pono Choices: a collaborative approach to developing a culturally
      responsive teen pregnancy and sexually transmitted infections prevention
      curriculum in Hawai'i.
AB  - The overall extent of evidence-based culturally responsive health education
      programs targeting ethnic minority groups in Hawai'i is limited. The few that do
      exist were adapted from models developed with other majority ethnic groups in
      mind and may not always be appropriate for Native Hawaiian or Pacific Islander
      youth (Okamoto et al. in J Alcohol Drug Educ 54(1):56-75, 2010; Helm and Baker in
      J Ethn Cult Divers Soc Work 20(2):131-149, 2011; Po'a-Kekuawela et al. in J Ethn
      Cult Divers Soc Work 18(3):242-258, 2009). The need for a culturally responsive,
      evidence-based health curriculum is clear considering the large disparities
      reported among Hawaiian youth in health, academic achievement, and other
      identified risk factors. School-based health interventions are an opportunity not
      only to improve the physical well being of students, but also to increase their
      ability to learn and succeed in school. The University of Hawai'i at Manoa-Center
      on Disability Studies (UH-CDS) received a highly competitive grant from the US
      Office of Adolescent Health to develop a teen pregnancy and sexually transmitted
      infection (STI) prevention curriculum for Hawai'i middle school youth. The
      authors will detail a collaborative process that led to a culturally responsive
      sexual health curriculum for middle school youth designed to meet the rigorous
      standards of an evidenced-based review and more importantly reduce teen
      pregnancies and STI transmission. 

PMID- 24293267
TI  - Neural mechanisms of discourse comprehension: a human lesion study.
AB  - Discourse comprehension is a hallmark of human social behaviour and refers to the
      act of interpreting a written or spoken message by constructing mental
      representations that integrate incoming language with prior knowledge and
      experience. Here, we report a human lesion study (n = 145) that investigates the
      neural mechanisms underlying discourse comprehension (measured by the Discourse
      Comprehension Test) and systematically examine its relation to a broad range of
      psychological factors, including psychometric intelligence (measured by the
      Wechsler Adult Intelligence Scale), emotional intelligence (measured by the
      Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits
      (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores
      obtained from these factors were submitted to voxel-based lesion-symptom mapping
      to elucidate their neural substrates. Stepwise regression analyses revealed that
      working memory and extraversion reliably predict individual differences in
      discourse comprehension: higher working memory scores and lower extraversion
      levels predict better discourse comprehension performance. Lesion mapping results
      indicated that these convergent variables depend on a shared network of frontal
      and parietal regions, including white matter association tracts that bind these
      areas into a coordinated system. The observed findings motivate an integrative
      framework for understanding the neural foundations of discourse comprehension,
      suggesting that core elements of discourse processing emerge from a distributed
      network of brain regions that support specific competencies for executive and
      social function. 

PMID- 24293269
TI  - Sport-specific balance.
AB  - This review includes the latest findings based on experimental studies addressing
      sport-specific balance, an area of research that has grown dramatically in recent
      years. The main objectives of this work were to investigate the postural sway
      response to different forms of exercise under laboratory and sport-specific
      conditions, to examine how this effect can vary with expertise, and to provide
      examples of the association of impaired balance with sport performance and/or
      increasing risk of injury. In doing so, sports where body balance is one of the
      limiting factors of performance were analyzed. While there are no significant
      differences in postural stability between athletes of different specializations
      and physically active individuals during standing in a standard upright position
      (e.g., bipedal stance), they have a better ability to maintain balance in
      specific conditions (e.g., while standing on a narrow area of support).
      Differences in magnitude of balance impairment after specific exercises (rebound
      jumps, repeated rotations, etc.) and mainly in speed of its readjustment to
      baseline are also observed. Besides some evidence on an association of greater
      postural sway with the increasing risk of injuries, there are many myths related
      to the negative influence of impaired balance on sport performance. Though this
      may be true for shooting or archery, findings have shown that in many other
      sports, highly skilled athletes are able to perform successfully in spite of
      increased postural sway. These findings may contribute to better understanding of
      the postural control system under various performance requirements. It may
      provide useful knowledge for designing training programs for specific sports. 

PMID- 24293270
TI  - Novel on-demand bioadhesion to soft tissue in wet environments.
AB  - Current methods of tissue fixation rely on mechanical-related technologies
      developed from the clothing and carpentry industries. Herein, a novel bioadhesive
      method that allows tuneable adhesion and is also applicable to biodegradable
      polyester substrates is described. Diazirine is the key functional group that
      allows strong soft tissue crosslinking and on-demand adhesion based on a free
      radical mechanism. Plasma post-irradiation grafting makes it possible to graft
      diazirine onto PLGA substrates. When the diazirine-PLGA films, placed on wetted
      ex vivo swine aortas, are activated with low intensity UV light, lap shear
      strength of up to 450 +/- 50 mN cm(-2) is observed, which is one order of
      magnitude higher than hydrogel bioadhesives placed on similar soft tissues. The
      diazirine-modified PLGA thin films could be added on top of previously developed
      technologies for minimally invasive surgeries. The present work is focused on the
      chemistry, grafting, and lap shear strength of the alkyl diazirine-modified PLGA
      bioadhesive films.

PMID- 24293271
TI  - Highly size-selective ionically crosslinked multilayer polymer films for light
      gas separation.
AB  - Exceptionally high hydrogen permselectivity, exceeding that of any polymeric or
      porous inorganic systems, is achieved using an ionically crosslinked multilayer
      polymer thin film. 

PMID- 24293272
TI  - What are the qualifications and selection criteria for women to be appointed to
      society journal editorial boards?
AB  - Japan ranks extremely low in global ranking of gender equality. It is not easy
      for female doctors to acquire leadership positions in member societies of the
      Japanese Association of Medical Science (JAMS). Very few women are included on
      editorial boards of English medical journals in Japan. Furthermore, until last
      year, there had been no female editors in English language journals of surgical
      societies. The qualifications and criteria for selecting editorial board members
      of medical journals should be clarified. Medical journals in Japan would gain
      diversity by including women on editorial boards in the same proportion as women
      membership in the corresponding medical societies. 

PMID- 24293273
TI  - Anterolateral approach for minimally invasive aortic valve replacement.
AB  - OBJECTIVE: Right anterior thoracotomy is the most common approach of minimally
      invasive aortic valve replacement (MIAVR) via intercostal mini-thoracotomy.
      However, there are some disadvantages including sacrificing the right internal
      thoracic artery (RITA). The aim of the present study was to investigate the
      efficacy of anterolateral thoracotomy (ALT), which is similar to lateral
      thoracotomy used for minimally invasive mitral valve surgery, for MIAVR. METHODS:
      From October 2012 to June 2013, 21 patients underwent MIAVR through ALT.
      Perioperative outcome of these patients was compared with those of 59 patients
      who underwent MIAVR via standard anterior thoracotomy (SAT) from May 2007 to
      September 2012. RESULTS: Mean age, body surface area, annular size, the ratio of
      aortic stenosis, and Japan score (30 days mortality), in ALT group were
      significantly more severe than those in SAT group. There was no significant
      difference in operative time; however, cardiopulmonary bypass and cross-clamping
      times in ALT group were significantly longer than those in SAT group. Significant
      differences were not found in mortality, morbidity, intubation time, blood
      transfusion rate, intensive care unit stay, hospital stay, and echocardiographic
      data such as effective orifice area index between both groups. CONCLUSIONS:
      Anterolateral approach has several advantages including no need to sacrifice the
      RITA and cosmetic benefit in female patients, offering similar results as SAT
      even with more severe patient characteristics.

PMID- 24293274
TI  - MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by
      targeting KRAS, PIK3CD and BCL2.
AB  - Colorectal cancer (CRC) is the third most common cancer in the USA. MicroRNAs
      play important roles in the pathogenesis of CRC. In this study, we investigated
      the role of miR-30b in CRC and found that its expression was significantly lower
      in CRC tissues than that in normal tissues. We showed that a low expression level
      of miR-30b was closely related to poor differentiation, advanced TNM stage and
      poor prognosis of CRC. Further experiments showed that over-expression of miR-30b
      suppressed CRC cell proliferation in vitro and tumour growth in vivo.
      Specifically, miR-30b promoted G1 arrest and induced apoptosis. Moreover, KRAS,
      PIK3CD and BCL2 were identified as direct and functional targets of miR-30b. MiR
      30b directly targeted the 3'-untranslated regions of their mRNAs and repressed
      their expression. This study revealed functional and mechanistic links between
      miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of CRC. MiR-30b
      not only plays important roles in the regulation of cell proliferation and tumour
      growth in CRC, but is also a potential prognostic marker or therapeutic target
      for CRC. Restoration of miR-30b expression may represent a promising therapeutic
      approach for targeting malignant CRC.

PMID- 24293275
TI  - Identification of novel rab27a/melanophilin blockers by pharmacophore-based
      virtual screening.
AB  - Melanocytes are unique cells that produce specific melanin-containing
      intracellular organelles called melanosomes. Melanosomes are transported from the
      perinuclear area of melanocytes toward the plasma membrane as they become more
      melanized in order to increase skin pigmentation. In this vesicular trafficking
      of melanosomes, Rab27a, melanophilin, and myosin Va play crucial roles in linking
      melanosomes to actin-based motors. To identify novel compounds to inhibit binding
      interface between Rab27a and melanophilin, a pharmacophore model was built based
      on a modeled 3D structure of the protein complex that describes the essential
      binding residues in the intermolecular interaction. A pharmacophore model was
      employed to screen a chemical library database. Finally, 25 virtual hits were
      selected for biological evaluations. The biological activities of 11 analogues
      were evaluated in a second assay. Two compounds were identified as having
      concentration-dependent inhibitory activity. By analyzing structure-activity
      relationships of derivatives of BMD-20, two hydroxyl functional groups were found
      to be critical for blocking the intermolecular binding between Rab27a and
      melanophilin. 

PMID- 24293276
TI  - An indigenous hyperproductive species of Aureobasidium pullulans RYLF-10:
      influence of fermentation conditions on exopolysaccharide (EPS) production.
AB  - In recent years, a significant interest has been generated in discovering and
      developing exopolysaccharides (EPS) produced by microorganisms, especially fungi
      due to their multifaceted industrial and pharmacological applications. A number
      of filamentous and cellular fungi have been explored for this; however, according
      to the existing literature, the work on exopolysaccharide production by
      indigenous culture on this aspect is still very less and requires a serious
      attention. The present work is an attempt in this regard and aims to optimize the
      submerged culture conditions to produce the exopolysaccharides from an indigenous
      yeast Aureobasidium pullulans RYLF-10 with respect to several operating
      parameters in shake flask fermentation. The yeast A. pullulans RYLF-10 was
      identified by 18s RNA sequencing and detailed study on its nutritional
      requirements, and environmental conditions for submerged culture have been
      optimized. The optimal temperature and pH for both the vegetative growth and EPS
      production were found to be 28 +/- 1  degrees C and 5.0, respectively, while the
      agitation speed and inoculum size were reported to be 150 rpm and 1 % (v/v),
      respectively. Sucrose (50 g/l) and yeast extract (1 g/l) were found to be the
      most suitable carbon and nitrogen sources which worked best in the ratio of 60:1
      and resulted in the maximum EPS yield. Similarly, the other variables like growth
      regulator (riboflavin) and minerals (NaCl + K2HPO4 + MgSO4) altogether resulted
      in a noteworthy EPS yield of 45.24 g/l which is the maximum yield from this
      indigenous isolate of A. pullulans RYLF-10.

PMID- 24293277
TI  - A review on optimization production and upgrading biogas through CO2 removal
      using various techniques.
AB  - Biogas from anaerobic digestion of organic materials is a renewable energy
      resource that consists mainly of CH4 and CO2. Trace components that are often
      present in biogas are water vapor, hydrogen sulfide, siloxanes, hydrocarbons,
      ammonia, oxygen, carbon monoxide, and nitrogen. Considering the biogas is a clean
      and renewable form of energy that could well substitute the conventional source
      of energy (fossil fuels), the optimization of this type of energy becomes
      substantial. Various optimization techniques in biogas production process had
      been developed, including pretreatment, biotechnological approaches, co-digestion
      as well as the use of serial digester. For some application, the certain purity
      degree of biogas is needed. The presence of CO2 and other trace components in
      biogas could affect engine performance adversely. Reducing CO2 content will
      significantly upgrade the quality of biogas and enhancing the calorific value.
      Upgrading is generally performed in order to meet the standards for use as
      vehicle fuel or for injection in the natural gas grid. Different methods for
      biogas upgrading are used. They differ in functioning, the necessary quality
      conditions of the incoming gas, and the efficiency. Biogas can be purified from
      CO2 using pressure swing adsorption, membrane separation, physical or chemical
      CO2 absorption. This paper reviews the various techniques, which could be used to
      optimize the biogas production as well as to upgrade the biogas quality. 

PMID- 24293278
TI  - Hepcidin production in response to iron is controlled by monocyte-derived humoral
      factors.
AB  - Hepcidin, which is mainly produced by the liver, is the key regulator in iron
      homeostasis. Hepcidin expression is up-regulated by iron loading in vivo, but the
      mechanism underlying this process is not completely understood. In the present
      study, we investigated the mechanism, following the hypothesis that hepcidin
      production in response to iron loading is regulated by extra-hepatic iron
      sensors. We measured serum hepcidin concentrations and iron indices in Wistar
      rats treated with saccharated ferric oxide (SFO). Human hepatoma-derived HepG2
      cells were stimulated using SFO-administered rat sera, and co-cultured with rat
      spleen cells, human monocyte-derived THP-1 cells, or human monocytes with
      diferric transferrin (holo-Tf), and hepcidin concentrations in the conditioned
      media were measured. SFO elevated rat serum hepcidin concentrations. SFO-treated
      rat sera increased hepcidin production from HepG2 cells, and this induction
      correlated with serum hepcidin levels, but not with iron indices. Holo-Tf up
      regulated hepcidin concentrations in media from HepG2 cells co-cultured with rat
      spleen cells, THP-1 cells, or human monocytes with or without cell-to-cell
      contacts, while holo-Tf did not up-regulate hepcidin from HepG2 cells alone. Our
      results suggest the existence of humoral factors capable of inducing hepcidin
      production that are secreted by extra-hepatic cells, such as reticuloendothelial
      monocytes, in response to iron. 

PMID- 24293279
TI  - Expression of different functional isoforms in haematopoiesis.
AB  - Haematopoiesis is a complex process regulated at various levels facilitating
      rapid responses to external factors including stress, modulation of lineage
      commitment and terminal differentiation of progenitors. Although the
      transcription program determines the RNA pool of a cell, various mRNA strands can
      be obtained from the same template, giving rise to multiple protein isoforms. The
      majority of variants and isoforms co-occur in normal haematopoietic cells or are
      differentially expressed at various maturity stages of progenitor maturation and
      cellular differentiation within the same lineage or across lineages. Genetic
      aberrations or specific cellular states result in the predominant expression of
      abnormal isoforms leading to deregulation and disease. The presence of upstream
      open reading frames (uORF) in 5' untranslated regions (UTRs) of a transcript,
      couples the utilization of start codons with the cellular status and availability
      of translation initiation factors (eIFs). In addition, tissue-specific and cell
      lineage-specific alternative promoter use, regulates several transcription
      factors producing transcript variants with variable 5' exons. In this review, we
      propose to give a detailed account of the differential isoform formation, causing
      haematological malignancies. 

PMID- 24293280
TI  - Successful repeated treatment of acute myeloid leukemia in early relapse with
      gemtuzumab ozogamicin alone.
AB  - A 68-year-old female was diagnosed with acute myeloid leukemia (AML-M2 without
      8/21 translocation) in December 2006. Although a complete remission (CR) was
      obtained after induction chemotherapy, the first post-remission therapy was
      discontinued because of severe cardiovascular complications. She had a relapse of
      AML with CD33-positive myeloblasts which comprised 38.4 % of the bone marrow
      cells in November 2007. She received two courses of low-dose chemotherapy because
      of the previous complications. The amount of Wilm's tumor 1 (WT1) mRNA in the
      peripheral blood was 13,000 copies/MUg RNA after the first course of the
      chemotherapy, and 4.8 % myeloblasts remained in the bone marrow after the second
      course. She was treated with a single course of gemtuzumab ozogamicin (GO), with
      a subsequent CR with 0.9 % marrow myeloblasts and fewer than 50 copies of WT-1
      mRNA (normal level). Thereafter, she received five courses of GO monotherapy at
      each occasion of early AML relapse. Hematological remission has been sustained
      over a period of about 24 months with the GO monotherapy alone. This case
      suggests that GO monotherapy is a useful salvage therapy for early relapse of
      CD33-positive AML in situations in which standard chemotherapy is not indicated. 

PMID- 24293281
TI  - P wave duration and dispersion in Holter electrocardiography of patients with
      obstructive sleep apnea.
AB  - PURPOSE: The underlying mechanisms of the association between obstructive sleep
      apnea (OSA) and atrial fibrillation (AF) remained unclear. We investigated P wave
      parameters as indicators of atrial conduction status among OSA patients. METHODS:
      We studied 42 untreated OSA patients, categorized into mild (6), moderate (18),
      and severe (18) OSA based on the apnea/hypopnea index (AHI) and 18 healthy
      controls. Twenty-four-hour Holter electrocardiography was applied to measure P
      wave parameters including P wave duration and P wave dispersion; difference
      between the maximum (P-max) and minimum (P-min) measured P wave duration.
      RESULTS: Mean P wave duration ranged from 110.2 +/- 9.3 ms in mild OSA patients
      to 121.1 +/- 15.4 ms in severe OSA patients and was 113.4 +/- 10.0 ms in controls
      with no significant difference among the groups, P = 0.281. P wave dispersion and
      P-max were significantly longer in those with moderate OSA (68.0 +/- 9.3 and
      154.2 +/- 9.3 ms) and those with severe OSA (71.6 +/- 13.7 and 157.2 +/- 13.3 ms)
      than controls (52.6 +/- 15.3 and 142.1 +/- 15.4 ms), P < 0.05. AHI was
      significantly correlated with P-max (r = 0.407, P = 0.012) and P wave dispersion
      (r = 0.431, P = 0.008). With linear regression analysis controlling for age,
      gender, and BMI, the AHI was independently associated with P wave dispersion
      (beta = 0.482, P = 0.002). CONCLUSIONS: Using Holter monitoring for measurement
      of P wave parameters, this study showed an association of OSA with prolonged P
      max and P wave dispersion. These results indicate that patients with OSA have
      disturbances in atrial conduction associated with OSA severity. Repeating this
      study in a larger sample of patients is warranted.

PMID- 24293282
TI  - Challenges in measuring medication adherence: experiences from a controlled
      trial.
AB  - Measurement of adherence is complex and many methods, both direct and indirect
      are used; there is no universal gold standard. In this article, we share our
      experiences in a randomised controlled study, the Hypertension Adherence Program
      in Pharmacy trial, evaluating a community pharmacy-based intervention for
      improving adherence to antihypertensive medication. Several objective and
      subjective measures of adherence (Morisky score, TABS score, MedsIndex, Medicines
      Possession Ratio) were used, but produced varying results, limiting confidence in
      the conclusions that could be drawn. Despite using a specifically designed data
      mining software program to identify potentially nonadherent patients from
      dispensing records, many participants were found to be adherent by the self
      reported Morisky scale. A lesson to be learned when targeting people for
      interventions to improve adherence is that information from dispensing records
      should be supplemented by other methods in order to identify patients most in
      need of assistance. 

PMID- 24293284
TI  - A method for calculating adherence to polypharmacy from dispensing data records.
AB  - BACKGROUND: Several measures for calculating adherence to one medication from
      dispensing data records have been proposed, but the nomenclature is inconsistent
      and computations vary. The same measures, like the medication possession ratio
      (MPR), have been used for multiple medication regimens, and have tended to over-
      or under-estimate adherence rates. OBJECTIVE: To demonstrate the impact of
      varying elements in MPR to a single medication regimen; to define standards for
      the estimation of adherence to polypharmacy; to propose a new method for
      calculating adherence to polypharmacy; to face validate it. SETTING: Face
      validity of the proposed method. METHOD: Variations in the MPR formula were
      simulated. Standards for the estimation of adherence to polypharmacy were
      defined. A new method to calculate adherence to polypharmacy was established. Its
      face validity with three illustrative cases obtained from a pharmacy refill
      database was assessed. MAIN OUTCOME MEASURE: Adherence rate to polypharmacy from
      refill data records. RESULTS: MPR to a single medication is operationalized in
      the numerator and denominator and is influenced by the parameters like
      observation period, medication gaps, overlap. For polypharmacy, an average MPR is
      commonly used, which is not accounting for the specificity of multiple
      medications, and hence overestimating adherence rate. We propose the daily
      polypharmacy possession ratio (DPPR) as an index of adherence to polypharmacy. It
      estimates the proportion of time a patient had medication available for use by
      considering the presence or absence of multiple medications on each day in the
      observation period. We calculated possession rates from refill histories over 31
      months (January 1, 2011-July 31, 2013) for three illustrative patients. The
      average MPR estimates were 80 % for a patient with 6 medications/20 refill dates,
      90 % for a patient with 4 medications/11 refill dates, and 89 % for a patient
      with 3 medications/17 refill dates. The corresponding DPPRs were 75, 88 and 99 %,
      indicating overestimations by 5 and 2 %, and underestimation by 10 %,
      respectively. CONCLUSION: The DPPR accounts for the specificity of polypharmacy
      including number of medications, medication switching, duplication, overlapping.
      Research is needed to further confirm the validity of this new index.

PMID- 24293285
TI  - Seed treatments to control seedborne fungal pathogens of vegetable crops.
AB  - Vegetable crops are frequently infected by fungal pathogens, which can include
      seedborne fungi. In such cases, the pathogen is already present within or on the
      seed surface, and can thus cause seed rot and seedling damping-off. Treatment of
      vegetable seeds has been shown to prevent plant disease epidemics caused by
      seedborne fungal pathogens. Furthermore, seed treatments can be useful in
      reducing the amounts of pesticides required to manage a disease, because
      effective seed treatments can eliminate the need for foliar application of
      fungicides later in the season. Although the application of fungicides is almost
      always effective, their non-target environmental impact and the development of
      pathogen resistance have led to the search for alternative methods, especially in
      the past few years. Physical treatments that have already been used in the past
      and treatments with biopesticides, such as plant extracts, natural compounds and
      biocontrol agents, have proved to be effective in controlling seedborne
      pathogens. These have been applied alone or in combination, and they are widely
      used owing to their broad spectrum in terms of disease control and production
      yield. In this review, the effectiveness of different seed treatments against the
      main seedborne pathogens of some important vegetable crops is critically
      discussed.

PMID- 24293286
TI  - Biparietal diameter at 11 to 13 weeks' gestation in fetuses with
      holoprosencephaly.
AB  - OBJECTIVE: Studies have suggested that fetuses with holoprosencephaly have
      smaller head size, demonstrated as early as the first trimester. However, the
      majority of these cases were diagnosed in the second or third trimesters. The aim
      of this study was to investigate biparietal diameter (BPD) measured at 11 to 13
      weeks' gestation in fetuses with holoprosencephaly. METHODS: This was a
      retrospective study in which BPD was measured at 11 to 13 weeks in 34 fetuses
      with prenatal diagnosis of holoprosencephaly and 7775 unaffected controls. BPD
      values were converted into multiples of the expected median (MoM) after
      adjustment for crown-rump length and maternal characteristics. RESULTS: The
      median gestational age at the BPD recording was 12.6 (interquartile range 12.3
      13.0) weeks. The nuchal translucency was increased (>=3mm) in 58.8% of the cases.
      Aneuploidy was confirmed in 73.5% of the cases; the commonest was trisomy 13
      (50.0%). BPD values at 11 to 13 weeks were below the 5(th) centile in 32.4% of
      cases and below the 50(th) centile in 67.6%. BPD MoM values were significantly
      smaller than in the control group (median: 0.98; interquartile range: 0.90-1.06
      vs 1.00; 0.96-1.04 MoM, p = 0.03). CONCLUSION: Fetuses with holoprosencephaly
      have a smaller BPD in the first trimester. This property may be useful in early
      diagnosis.

PMID- 24293288
TI  - Directed water shedding on high-aspect-ratio shape memory polymer micropillar
      arrays.
AB  - A reconfigurable, droplet-directing surface is developed based on high-aspect
      ratio shape-memory polymer (SMP) pillars. The water droplet on the original or
      recovered SMP pillars can slide off the surface at a finite angle of inclination
      while being fully pinned on the deformed pillar array. This wettability contrast
      allows directed water shredding from the straight pillars to the deformed ones. 

PMID- 24293287
TI  - The effects of shRNA-mediated gene silencing of transcription factor SNAI1 on the
      biological phenotypes of breast cancer cell line MCF-7.
AB  - To research the effects of silencing transcription factor SNAI1 on the in vitro
      biological phenotypes of breast cancer cell line MCF-7, based on the gene
      sequence of SNAI1, we linked shRNA with the green fluorescent protein-expressing
      eukaryotic expression vector pGCsilencerTM U6/Neo/GFP, and transfected it into
      MCF-7 cells. The SNAI1 gene-silencing effect was authenticated by RT-PCR and
      immunofluorescence. We then examined the effect of gene silencing on the
      expression of epithelial and mesenchymal markers and on their biological
      phenotypes of the target cells. Finally, we explained that SNAI1 was bound to E
      cadherin in MCF-7 cells by ChIP. Silencing SNAI1 upregulated the expression of
      epithelial markers claudin-4, claudin-7, and E-cadherin, while expression of the
      mesenchymal marker matrix metalloproteinase-2 was downregulated. The capacity for
      proliferation, migration, and invasion was diminished. SNAI1 binds to the E
      cadherin gene promoter and inhibits its transcription. We can conclude that
      silencing gene SNAI1 inhibits expression of properties that are associated with
      the malignant phenotype of MCF-7 cells and reverses the epithelial-mesenchymal
      transition process by regulating relevant target gene E-cadherin. 

PMID- 24293289
TI  - Angiographic evaluation of graft patency in robotic-assisted coronary artery
      bypass surgery: 8 year follow-up.
AB  - BACKGROUND: Robotic telemanipulation systems have emerged as facilitating tools
      that enhance minimally invasive cardiac surgery.The purpose of this study was to
      evaluate graft patency by a combination of invasive and non-invasive coronary
      angiography methods in robotic-assisted coronary artery surgery(CABG) for optimal
      quality control. METHODS: Between April 2004 and February 2012, patients who had
      robotic-assisted CABG were called to have cardiac catheterization or multislice
      computed tomographic angiography to evaluate graft patency. RESULTS: One hundred
      patients out of a total 250 cases were followed for graft patency for a mean
      period of 60.3 +/- 23.8 (range 12-94) months. Mean operative time and left
      internal mammary artery harvest time was 165.96 +/- 19.5 and 41.74 +/- 5.9 (range
      30-55) min. Postoperative graft patency rate was 94% and freedom from target
      vessel re-interventions was 98%. CONCLUSION: Robotic-assisted CABG can be
      accomplished with low morbidity, mortality and re-intervention rates. It is a
      safe procedure in selected patients and produces excellent mid-term graft
      patency.

PMID- 24293290
TI  - Tissue engineering and regenerative medicine approaches to enhance the functional
      response to skeletal muscle injury.
AB  - The well-recognized ability of skeletal muscle for functional and structural
      regeneration following injury is severely compromised in degenerative diseases
      and in volumetric muscle loss. Tissue engineering and regenerative medicine
      strategies to support muscle reconstruction have typically been cell-centric with
      approaches that involve the exogenous delivery of cells with myogenic potential.
      These strategies have been limited by poor cell viability and engraftment into
      host tissue. Alternative approaches have involved the use of biomaterial
      scaffolds as substrates or delivery vehicles for exogenous myogenic progenitor
      cells. Acellular biomaterial scaffolds composed of mammalian extracellular matrix
      (ECM) have also been used as an inductive niche to promote the recruitment and
      differentiation of endogenous myogenic progenitor cells. An acellular approach,
      which activates or utilizes endogenous cell sources, obviates the need for
      exogenous cell administration and provides an advantage for clinical translation.
      The present review examines the state of tissue engineering and regenerative
      medicine therapies directed at augmenting the skeletal muscle response to injury
      and presents the pros and cons of each with respect to clinical translation.

PMID- 24293291
TI  - WITHDRAWN: Prophylactic antibiotic therapy for chronic bronchitis.

PMID- 24293292
TI  - Chromium picolinate supplementation for overweight or obese adults.
AB  - BACKGROUND: Obesity is a global public health threat. Chromium picolinate (CrP)
      is advocated in the medical literature for the reduction of bodyweight, and
      preparations are sold as slimming aids in the USA and Europe, and on the
      Internet. OBJECTIVES: To assess the effects of CrP supplementation in overweight
      or obese people. SEARCH METHODS: We searched The Cochrane Library, MEDLINE,
      EMBASE, ISI Web of Knowledge, the Chinese Biomedical Literature Database, the
      China Journal Full text Database and the Chinese Scientific Journals Full text
      Database (all databases to December 2012), as well as other sources (including
      databases of ongoing trials, clinical trials registers and reference lists).
      SELECTION CRITERIA: We included trials if they were randomised controlled trials
      (RCT) of CrP supplementation in people who were overweight or obese.We excluded
      studies including children, pregnant women or individuals with serious medical
      conditions. DATA COLLECTION AND ANALYSIS: Two authors independently screened
      titles and abstracts for relevance. Screening for inclusion, data extraction and
      'Risk of bias'assessment were carried out by one author and checked by a second.
      We assessed the risk of bias by evaluating the domains selection,performance,
      attrition, detection and reporting bias. We performed a meta-analysis of included
      trials using Review Manager 5. MAIN RESULTS: We evaluated nine RCTs involving a
      total of 622 participants. The RCTs were conducted in the community setting, with
      interventions mainly delivered by health professionals, and had a short- to
      medium-term follow up (up to 24 weeks). Three RCTs compared CrPplus resistance or
      weight training with placebo plus resistance or weight training, the other RCTs
      compared CrP alone versus placebo.We focused this review on investigating which
      dose of CrP would prove most effective versus placebo and therefore assessed the
      results according to CrP dose. However, in order to find out if CrP works in
      general, we also analysed the effect of all pooled CrP doses versus placebo on
      body weight only.Across all CrP doses investigated (200 MUg, 400 MUg, 500 MUg,
      1000 MUg) we noted an effect on body weight in favour of CrP of debatable
      clinical relevance after 12 to 16 weeks of treatment: mean difference (MD) -1.1
      kg (95% CI -1.7 to -0.4); P = 0.001; 392 participants;6 trials; low-quality
      evidence (GRADE)). No firm evidence and no dose gradient could be established
      when comparing different doses of CrP with placebo for various weight loss
      measures (body weight, body mass index, percentage body fat composition, change
      in waist circumference).Only three studies provided information on adverse events
      (low-quality evidence (GRADE)). There were two serious adverse events and study
      dropouts in participants taking 1000 MUg CrP, and one serious adverse event in an
      individual taking 400 MUg CrP. Two participants receiving placebo discontinued
      due to adverse events; one event was reported as serious. No study reported on
      all-cause mortality,morbidity, health-related quality of life or socioeconomic
      effects. AUTHORS' CONCLUSIONS: We found no current, reliable evidence to inform
      firm decisions about the efficacy and safety of CrP supplements in overweight or
      obese adults.

PMID- 24293293
TI  - Whole-exome sequencing of pancreatic neoplasms with acinar differentiation.
AB  - Pancreatic carcinomas with acinar differentiation, including acinar cell
      carcinoma, pancreatoblastoma and carcinomas with mixed differentiation, are
      distinct pancreatic neoplasms with poor prognosis. Although recent whole-exome
      sequencing analyses have defined the somatic mutations that characterize the
      other major neoplasms of the pancreas, the molecular alterations underlying
      pancreatic carcinomas with acinar differentiation remain largely unknown. In the
      current study, we sequenced the exomes of 23 surgically resected pancreatic
      carcinomas with acinar differentiation. These analyses revealed a relatively
      large number of genetic alterations at both the individual base pair and
      chromosomal levels. There was an average of 119 somatic mutations/carcinoma. When
      three outliers were excluded, there was an average of 64 somatic mutations/tumour
      (range 12-189). The mean fractional allelic loss (FAL) was 0.27 (range 0-0.89)
      and heterogeneity at the chromosome level was confirmed in selected cases using
      fluorescence in situ hybridization (FISH). No gene was mutated in >30% of the
      cancers. Genes altered in other neoplasms of the pancreas were occasionally
      targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six
      tumours (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1
      in one (4%). Somatic mutations were identified in genes in which constitutional
      alterations are associated with familial pancreatic ductal adenocarcinoma, such
      as ATM, BRCA2 and PALB2 (one tumour each), as well as in genes altered in extra
      pancreatic neoplasms, such as JAK1 in four tumours (17%), BRAF in three (13%),
      RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3
      in two (9%) and BAP1 in one (4%). Perhaps most importantly, we found that more
      than one-third of these carcinomas have potentially targetable genetic
      alterations, including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1.

PMID- 24293294
TI  - Risk factors for hospital-acquired bloodstream infections caused by extended
      spectrum beta-lactamase Klebsiella pneumoniae among cancer patients.
AB  - BACKGROUND: Incidence of infection due to extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae (ESBL-KP) has increased rapidly in recent years.
      However, its prevalence in cancer patients is seldom reported. AIMS: This study
      was designed to identify the risk factors for bloodstream infections (BSIs) with
      ESBL-KP, and to understand its susceptibility among cancer patients on
      antibiotics. METHODS: We conducted a retrospective study with a total of 118
      cancer patients between 2009 and 2011 with BSIs, among which 88 were infected
      with non-ESBL-KP and 30 with ESBL-KP. Patterns of susceptibility, clinical
      characteristics and mortality were investigated. Multivariate logistic regression
      model was used to unveil independent risk factors. RESULTS: On multivariate
      analysis, length of stay (LOS) (p = 0.025), and prior exposure to cephalosporins
      (p = 0.006), fluoroquinolones (p = 0.011), macrolides (p = 0.007) and
      aminoglycosides (p = 0.008) were independent risk factors for BSIs of ESBL-KP.
      For mortality, there was no significant difference between ESBL-KP and non-ESBL
      KP groups (p = 0.431). Moreover, compared with non-ESBL-KP, ESBL-KP displayed
      reduced sensitivity to aminoglycosides (p < 0.001, except amikacin),
      fluoroquinolones (p < 0.001), piperacillin-tazobactam (p = 0.005) and
      trimethoprim-sulfamethoxazole (p < 0.001), respectively. CONCLUSIONS: ESBL-KP
      exhibited less susceptibility to various non-beta-lactamase antibiotics, and
      infections due to these organisms were related to LOS and preexisting use of
      antibiotics. Thus, judicious use of all antibiotics should be underscored to
      reduce the infections caused by ESBL-KP.

PMID- 24293295
TI  - Protective effect of CDP-choline on ischemia-reperfusion-induced myocardial
      tissue injury in rats.
AB  - BACKGROUND: CDP-choline exerts tissue protective effect in several ischemic
      conditions. Recently we have reported that the drug prevents cardiac arrhythmias
      and improves survival rate in short-term myocardial ischemia reperfusion in rats.
      AIM: In the current study, we determined the effect of intravenously administered
      CDP-choline on myocardial tissue injury induced by 30-min ischemia followed by 3
      h reperfusion in anesthetized rats. METHODS: Myocardial ischemia was produced by
      ligature of the left main coronary artery. CDP-choline (100-500 mg/kg) was
      intravenously injected in the middle of the ischemic period. Cardiovascular
      parameters were recorded through the experimental period. At the end of the
      reperfusion period, the hearts of the animals were removed and stained for the
      investigation of tissue necrosis and apoptosis. The infarct size was evaluated as
      the ratio of the infarct area to the risk area. Apoptotic activation was assessed
      by TUNEL assay. Also the blood samples of rats were collected for the measurement
      of M30-M65, ADMA, homocysteine, and lactate levels. RESULTS: Ischemia/reperfusion
      caused serious injury in myocardium, increased blood ADMA and lactate levels
      without influencing other parameters. CDP-choline significantly reduced the
      infarct size and the number of apoptotic cells in the risk area. Blood pressure
      increased after CDP-choline injection; however, it returned back to the basal
      levels before the onset of reperfusion. CDP-choline failed to alter any other
      measured parameters. CONCLUSION: The present results demonstrate that
      intravenously administered CDP-choline is able to protect myocardium from injury
      induced by long-term coronary occlusion-reperfusion in rats. The inhibition of
      apoptosis by the drug may contribute to its protective effect. But neither the
      increase in blood pressure in response to CDP-choline injection nor changes in
      plasma ADMA concentration appear to mediate the attenuation of the myocardial
      injury.

PMID- 24293296
TI  - Metal oxide-coated anodes in wastewater treatment.
AB  - Electrochemical oxidation is an effective wastewater treatment method. Metal
      oxide-coated substrates are commonly used as anodes in this process. This article
      compiles the developments in the fabrication, application, and performance of
      metal oxide anodes in wastewater treatment. It summarizes the preparative methods
      and mechanism of oxidation of organics on the metal oxide anodes. The discussion
      is focused on the application of SnO2, PbO2, IrO2, and RuO2 metal oxide anodes
      and their effectiveness in wastewater treatment process. 

PMID- 24293297
TI  - Decolourisation of Acid Orange 7 recalcitrant auto-oxidation coloured by-products
      using an acclimatised mixed bacterial culture.
AB  - This study focuses on the biodegradation of recalcitrant, coloured compounds
      resulting from auto-oxidation of Acid Orange 7 (AO7) in a sequential facultative
      anaerobic-aerobic treatment system. A novel mixed bacterial culture, BAC-ZS,
      consisting of Brevibacillus panacihumi strain ZB1, Lysinibacillus fusiformis
      strain ZB2, and Enterococcus faecalis strain ZL bacteria were isolated from
      environmental samples. The acclimatisation of the mixed culture was carried out
      in an AO7 decolourised solution. The acclimatised mixed culture showed 98 %
      decolourisation within 2 h of facultative anaerobic treatment using yeast extract
      and glucose as co-substrate. Subsequent aerobic post treatment caused auto
      oxidation reaction forming dark coloured compounds that reduced the percentage
      decolourisation to 73 %. Interestingly, further agitations of the mixed culture
      in the solution over a period of 48 h significantly decolourise the coloured
      compounds and increased the decolourisation percentage to 90 %. Analyses of the
      degradation compounds using UV-visible spectrophotometer, Fourier transform
      infrared spectroscopy (FTIR) and high performance liquid chromatography (HPLC)
      showed complete degradation of recalcitrant AO7 by the novel BAC-ZS.
      Phytotoxicity tests using Cucumis sativus confirmed the dye solution after post
      aerobic treatment were less toxic compared to the parent dye. The quantitative
      real-time PCR revealed that E. faecalis strain ZL was the dominant strain in the
      acclimatised mix culture.

PMID- 24293298
TI  - Effects of the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate on
      the growth of wheat seedlings.
AB  - Ionic liquids (ILs) are called "green" solvents, which are due to their unique
      physicochemical properties and potential applications in various areas. However,
      the toxicity of ILs has attracted increasing attention from scientific
      researchers. The present paper studied the toxic effects of 1-octyl-3
      methylimidazolium hexafluorophosphate ([C8mim]PF6) on wheat seedlings at 0, 1, 2,
      4, 6, and 8 mg l(-1) on days 7, 10 and 13. The present results showed that the
      growth of wheat seedlings was seriously inhibited when the concentration was
      higher than 2 mg l(-1) and the inhibitory effect enhanced with increasing
      concentration and time. The EC50 values for germination, shoot length, root
      length and dry weight were 11.104, 5.187, 4.380 and 6.292 mg l(-1), respectively.
      [C8mim]PF6 could cause an increase in the production of ROS, which led to the
      oxidative damage and lipid peroxidation. Furthermore, these toxic effects on
      wheat seedlings were irreversible.

PMID- 24293299
TI  - Air-soil exchange of PCBs: levels and temporal variations at two sites in Turkey.
AB  - Seasonal distribution of polychlorinated biphenyls (PCBs) at the air-soil
      intersection was determined for two regions: one with urban characteristics where
      traffic is dense (BUTAL) and the other representing the coastal zone (Mudanya).
      Fifty-one air and soil samples were simultaneously collected. Total PCB (Sigma82
      PCB) levels in the soil samples collected during a 1-year period ranged between
      105 and 7,060 pg/g dry matter (dm) (BUTAL) and 110 and 2,320 pg/g dm (Mudanya).
      Total PCB levels in the gaseous phase were measured to be between 100 and 910
      pg/m(3) (BUTAL) and 75 and 1,025 pg/m(3) (Mudanya). Variations in the
      concentrations were observed depending on the season. Though the PCB
      concentrations measured in the atmospheres of both regions in the summer months
      were high, they were found to be lower in winter. However, while soil PCB levels
      were measured to be high at BUTAL during summer months, they were found to be
      high during winter months in Mudanya. The direction and amount of the PCB
      movement were determined by calculating the gaseous phase change fluxes at air
      soil intersection. While a general PCB movement from soil to air was found for
      BUTAL, the PCB movement from air to soil was calculated for the Mudanya region in
      most of the sampling events. During the warmer seasons PCB movement towards the
      atmosphere was observed due to evaporation from the soil. With decreases in the
      temperature, both decreases in the number of PCB congeners occurring in the air
      and a change in the direction of some congeners were observed, possibly caused by
      deposition from the atmosphere to the soil. 3-CB and 4-CB congeners were found to
      be dominant in the atmosphere, and 4-, 5-, and 6-CBs were found to dominate in
      the surface soils.

PMID- 24293300
TI  - Lipase production from a novel thermo-tolerant and extreme acidophile Bacillus
      pumilus using palm oil as the substrate and treatment of palm oil-containing
      wastewater.
AB  - The thermo-tolerant and extreme acidophilic microorganism Bacillus pumilus was
      isolated from the soil collected from a commercial edible-oil extraction
      industry. Optimisation of conditions for the lipase production was conducted
      using response surface methodology. The optimum conditions for obtaining the
      maximum activity (1,100 U/mL) of extremely acidic thermostable lipase were
      fermentation time, 96 h; pH, 1; temperature, 50  degrees C; and concentration of
      palm oil, 50 g/L. After purification, a 7.1-fold purity of lipase with specific
      activity of 5,173 U/mg protein was obtained. The molecular weight of the thermo
      tolerant acidophilic lipase (TAL) was 55 kDa. The predominant amino acid in the
      TAL was glycine. The functional groups of lipase were determined by Fourier
      transform infrared spectroscopy. TAL exhibited enhanced activity (114 %) with
      dimethyl sulphoxide (20 %, v/v), and it showed a moderate activity with methanol,
      hexane and benzene. The optimum conditions for the treatment of palm oil in
      wastewater using the TAL were found to be time, 3 h; pH, 1; temperature, 50 
      degrees C with pseudo second-order kinetic constant of 1.88 * 10(-3) L mol(-1)
      min(-1). The Michaelis-Menten enzyme kinetic model and the nonlinear kinetic
      model were evaluated for the TAL. TAL established hydrolysis efficiency of 96 %
      for palm oil in wastewater at 50  degrees C.

PMID- 24293301
TI  - Occurrence and distribution of selected heavy metals and boron in groundwater of
      the Gulf of Khambhat region, Gujarat, India.
AB  - The concentration of selected heavy metals, like As, Co, Cr, Cu, Fe, Mn, Ni, Pb,
      and Zn as well as B, was measured by inductively coupled plasma-optical emission
      spectrometry (ICP-OES) in groundwater samples from various locations in the Gulf
      of Khambhat (GoK), an inlet of the Arabian Sea in the state of Gujarat, India,
      during post-monsoon, winter, and pre-monsoon seasons in a year. Most heavy
      elements are characterized by low mobility under slightly alkaline and reducing
      conditions; concentrations in confined aquifers are smaller than the maximum
      permissible values for drinking water. The temporal changes indicate that a
      majority of metals is entering the aquifer during monsoon. Principle component
      analysis of the heavy metal data suggests that Co, Cu, Cd, and Zn are
      interrelated with each other and derived significantly from anthropogenic route,
      while input of Pb and Cr may be due to atmospheric deposition in the study area.
      Both weathering of rocks and anthropogenic input were found to be main sources of
      elements in the groundwater. The heavy metal levels in groundwaters of the GoK
      region in comparison with some of the European and Asian sites were higher;
      however, these metal levels were found to be comparable with few urban sites in
      the world.

PMID- 24293302
TI  - Toward a robust analytical method for separating trace levels of nano-materials
      in natural waters: cloud point extraction of nano-copper(II) oxide.
AB  - Cloud point extraction (CPE) factors, namely Triton X-114 (TX-114) concentration,
      pH, ionic strength, incubation time, and temperature, were optimized for the
      separation of nano-sized copper(II) oxide (nCuO) in aqueous matrices. The
      kinetics of phase transfer was studied using UV-visible spectroscopy. From the
      highest separation rate, the most favorable conditions were observed with 0.2 %
      w/v of TX-114, pH = 9.0, ionic strength of 10 mM NaCl, and incubation at 40 
      degrees C for 60 min, yielding an extraction efficiency of 89.2 +/- 3.9 % and a
      preconcentration factor of 86. The aggregate size distribution confirmed the
      formation of very large nCuO-micelle assemblies (11.9 MUm) under these
      conditions. The surface charge of nCuO was also diminished effectively. An
      extraction efficiency of 91 % was achieved with a mixture of TX-100 and TX-114
      containing 30 wt.% of TX-100. Natural organic and particulate matters,
      represented by humic acid (30 mg/L) and micron-sized silica particles (50 mg/L),
      respectively, did not significantly reduce the CPE efficiency (<10 %). The
      recovery of copper(II) ions (20 mg/L) in the presence of humic acid was low (3-10
      %). The spiked natural water samples were analyzed either directly or after CPE
      by inductively coupled plasma mass spectrometry following acid
      digestion/microwave irradiation. The results indicated the influence of matrix
      effects and their reduction by CPE. A delay between spiking nCuO and CPE may also
      influence the recovery of nCuO due to aggregation and dissolution. A detection
      limit of 0.04 MUg Cu/L was achieved for nCuO.

PMID- 24293303
TI  - Solid malignant retroperitoneal masses-a pictorial review.
AB  - Primary retroperitoneal masses are a rare but important group of neoplasms. Cross
      sectional imaging has revolutionised the investigation of patients with
      retroperitoneal neoplasms. Both computed tomography (CT) and magnetic resonance
      imaging (MRI) can contribute to tumour diagnosis, though histological
      confirmation is often required because of the considerable overlap of imaging
      features. Cross-sectional imaging is key to the pre-operative staging and
      planning of retroperitoneal masses, though ultrasound may also help in certain
      instances. Imaging also helps to select and guide the site to biopsy from these
      usually large and heterogeneous neoplasms. This article aims to review many of
      the primary retroperitoneal neoplasms that may be encountered by the radiologist.

PMID- 24293304
TI  - Atypical ultrasound features of parathyroid tumours may bear a relationship to
      their clinical and biochemical presentation.
AB  - OBJECTIVES: To describe atypical ultrasound features of parathyroid lesions and
      correlate them with clinical presentation and histopathology. MATERIALS AND
      METHODS: Retrospective review of 264 patients with primary hyperparathyroidism
      who underwent ultrasound imaging prior to parathyroidectomy was performed.
      Patients with atypical ultrasound findings (n = 26) were identified; imaging
      findings were correlated with clinical presentation and histopathology. RESULTS:
      Twenty-one (80 %) lesions were adenomas, two (8 %) were adenomas with cellular
      atypia, and three (11.5 %) were carcinomas. Seventeen (65 %) lesions showed
      cystic change; five (19 %) of them had >50 % cystic change. These lesions were
      adenomas with cystic degeneration. Cystic degeneration had significant positive
      correlation with the lesion size and PTH level, but cystic adenomas correlated
      negatively with lesion weight. Six (23 %) lesions were isoechoic and one (4 %)
      was hyperechoic; histology predominantly revealed haemorrhage, hyalinisation and
      fibrosis; one lesion showed fat deposition and another had multiple granulomas
      within the adenoma. Twenty (83 %) lesions had heterogeneous echotexture and
      showed combinations of acinar dilatation, necrosis, haemorrhage and fibrosis.
      Heterogeneous lesions tended to be significantly larger and heavier, and they
      were associated with higher PTH levels. Four (15 %) lesions had calcifications.
      Scintigraphy was concordant in 22 (96 %), n = 23. One scintigraphy-negative
      lesion was a cystic parathyroid adenoma. CONCLUSION: Atypical ultrasound features
      of parathyroid lesions pose a diagnostic challenge. Awareness of these features
      would help improve lesion detection. TEACHING POINTS: 1. Cystic change is
      significantly related to the size, weight and measured parathyroid hormone
      levels. 2. Cystic change in parathyroid tumours indicated a slightly higher risk
      of malignancy. 3. Heterogeneous parathyroid adenomas are larger in size and
      heavier, and they have higher PTH levels. 4. Awareness of atypical ultrasound
      features will improve preoperative clinical prediction.

PMID- 24293305
TI  - The ESPACOMP and its role in promoting knowledge and competencies in the matter
      of patient adherence.

PMID- 24293306
TI  - Experiences of a community pharmacy service to support adherence and self
      management in chronic heart failure.
AB  - BACKGROUND: Heart failure (HF) is common, disabling and deadly. Patients with HF
      often have poor self-care and medicines non-adherence, which contributes to poor
      outcomes. Community pharmacy based cognitive services have the potential to help,
      but we do not know how patients view community-pharmacist-led services for
      patients with HF. OBJECTIVE: We aimed to explore and portray in detail, the
      perspectives of patients receiving, and pharmacists delivering an enhanced, pay
      for performance community pharmacy HF service. SETTING: Community pharmacies and
      community-based patients in Greater Glasgow and Clyde, Scotland. METHODS: Focus
      groups with pharmacists and semi-structured interviews with individual patients
      by telephone. Cross sectional thematic analysis of qualitative data used
      Normalization Process Theory to understand and describe patient's reports. MAIN
      OUTCOME MEASURE: Experiences of receiving and delivering an enhanced HF service.
      RESULTS: Pharmacists voiced their confidence in delivering the service and
      highlighted valued aspects including the structured consultation and repeated
      contacts with patients enabling the opportunity to improve self care and
      medicines adherence. Discussing co-morbidities other than HF was difficult and
      persuading patients to modify behaviour was challenging. Patients were
      comfortable discussing symptoms and medicines with pharmacists; they identified
      pharmacists as fulfilling roles that were needed but not currently addressed.
      Patients reported the service helped them to enact HF medicines and HF self care
      management strategies. CONCLUSION: Both patients receiving and pharmacists
      delivering a cognitive HF service felt that it addressed a shortfall in current
      care. There may be a clearly defined role for pharmacists in supporting patients
      to address the burden of understanding and managing their condition and
      treatment, leading to better self management and medicines adherence. This study
      may inform the development of strategies or policies to improve the process of
      care for patients with HF and has implications for the development of other
      extended role services.

PMID- 24293307
TI  - Evidence for compliance with long-term medication: a systematic review of
      randomised controlled trials.
AB  - BACKGROUND: Pharmacists play a pivotal role in optimising medication use which
      often includes actions to maximise compliance with long-term medication. The best
      evidence to support medication use is derived from randomised controlled trials
      (RCTs). It is often assumed that 100 % compliance is required to obtain the
      outcomes identified in the trial. This assumption needs to be examined.
      OBJECTIVE: To systematically review the reporting of compliance in RCTs of long
      term medications. METHOD: RCTs published in the New England Journal of Medicine,
      Journal of the American Medical Association, Lancet and BMJ in 2012, were
      reviewed to identify trials of medications for long-term use in adults. These
      trials were examined to evaluate the reporting of compliance. MAIN OUTCOME
      MEASURES: The proportion of trials reporting compliance data, the methods used,
      and the proportion of trials using more than one method to determine compliance.
      RESULTS: Of the 289 RCTs published in 2012, 25 assessed long-term medications in
      adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies
      used more than one method to measure compliance. Pill count was the most commonly
      reported method for measuring compliance, with patient reports and blood levels
      also being used. CONCLUSION: The reporting of compliance in RCTs is poor and the
      methodology inconsistent. The methods used overestimate compliance. If compliance
      in a clinical trial is low, the evidence for the effectiveness and most
      importantly safety of the medication(s) is questionable. Two or more methods, one
      of which is standardised, should be used to measure compliance in clinical
      trials. The requirement to report compliance should be included in publication
      guidelines.

PMID- 24293308
TI  - Wernicke encephalopathy in pediatric neuro-oncology: presentation of 2 cases and
      review of literature.
AB  - Wernicke encephalopathy represents a well-known entity characterized by a set of
      cognitive and neurologic alterations. Wernicke encephalopathy is rare and under
      recognized in childhood and may be fatal. Few cases have been documented in
      pediatric oncology. We report on 2 Wernicke encephalopathy cases that occurred in
      children having a brain tumor. The diagnosis of Wernicke encephalopathy was
      suggested by clinical manifestations associated with the typical radiologic
      findings and a laboratory evidence of thiamine deficiency. No large series have
      been published to support the evidence that pediatric malignancies represent a
      demonstrated factor of increased risk to develop a Wernicke encephalopathy.
      Moreover, the diagnosis may be even more difficult in brain tumors, considering
      the overlapping symptoms and the risk of encephalopathy related to both the
      disease and the treatment. Wernicke encephalopathy should be considered in all
      children with cancer presenting a neurologic deterioration, mainly in brain
      tumors. An early diagnosis is imperative for a prompt therapy that might prevent
      or minimize the irreversible brain damage related to this condition.

PMID- 24293309
TI  - Epileptic encephalopathy with continuous spike and wave during sleep associated
      to periventricular leukomalacia.
AB  - Periventricular leukomalacia is the most common type of brain injury in premature
      infants. Our aim is to describe the frequency and the features of epilepsy in a
      single-center population of 137 children with periventricular leukomalacia. Forty
      two of the 137 (31%) patients presented epilepsy. Twelve percent of these
      patients presented West syndrome, whereas 19% showed a pattern of continuous
      spike-waves during slow sleep syndrome. In the latter group, outcome was
      frequently unfavorable, with a greater number of seizures and more drug
      resistance. A significant association was found between epilepsy and neonatal
      seizures, spastic tetraplegia, and mental retardation. Although less common than
      in other forms of brain injury, epilepsy is nevertheless a significant
      complication in children with periventricular leukomalacia. The fairly frequent
      association with continuous spike-waves during slow sleep syndrome deserves
      particular attention: electroencephalographic sleep monitoring is important in
      order to provide early treatment and prevent further neurologic deterioration. 

PMID- 24293310
TI  - Neuropsychological findings in childhood narcolepsy.
AB  - Narcolepsy with cataplexy is a severely disabling disorder very often arising in
      childhood. Data on neuropsychological impairment in children are scant. We
      administered standardized neuropsychological tests to 13 children with narcolepsy
      with cataplexy. Overall, our patients displayed multiple patterns of cognitive
      and behavioral dysfunction, and often academic failure (7 cases out of 13). All
      children had a normal full intelligence quotient (IQ), but 3 patients presented a
      significantly higher and 2 a significantly lower Verbal IQ compared to
      Performance IQ, respectively. Mean sleep latency was significantly correlated (P
      < .05) to alertness functions. Eight patients displayed behavioral problems:
      emotional symptoms and conduct problems prevailed. Childhood narcolepsy with
      cataplexy represents a risk factor for subtle and heterogeneous cognitive
      impairments potentially resulting in academic failure, despite the normal IQ.
      These children also have a certain psychopathological risk. All this seems to be
      at least partially detached from the direct effects of daytime sleepiness. 

PMID- 24293311
TI  - Perspectives in multiphasic osteochondral tissue engineering.
AB  - Critical-sized osteochondral defects are clinically challenging, with limited
      treatment options available. By engineering osteochondral grafts using a
      patient's own cells and osteochondral scaffolds designed to facilitate cartilage
      and bone regeneration, osteochondral defects may be treated with less
      complications and better long-term clinical outcomes. Scaffolds can influence the
      development and structure of the engineered tissue, and there is an increased
      awareness that osteochondral tissue engineering concepts need to take the in vivo
      complexities into account in order to increase the likelihood of successful
      osteochondral tissue repair. The developing trend in osteochondral tissue
      engineering is the utilization of multiphasic scaffolds to recapitulate the
      multiphasic nature of the native tissue. Cartilage and bone have different
      structural, mechanical, and biochemical microenvironments. By designing
      osteochondral scaffolds with tissue-specific architecture, it may be possible to
      enhance osteochondral repair within shorter timeframe. While there are promising
      in vivo outcomes using multiphasic approaches, functional regeneration of
      osteochondral constructs still remains a challenge. In this review, we provide an
      overview of in vivo osteochondral repair studies that have taken place in the
      past three years, and define areas which needs improvement in future studies.

PMID- 24293312
TI  - Bioremediation of Cd by microbially induced calcite precipitation.
AB  - Contamination by Cd is a significant environmental problem. Therefore, we
      examined Cd removal from an environmental perspective. Ureolysis-driven calcium
      carbonate precipitation has been proposed for use in geotechnical engineering for
      soil remediation applications. In this study, 55 calcite-forming bacterial
      strains were newly isolated from various environments. Biomineralization of Cd by
      calcite-forming bacteria was investigated in laboratory-scale experiments. A
      simple method was developed to determine the effectiveness of microbially induced
      calcite precipitation (MICP). Using this method, we determined the effectiveness
      of biomineralization for retarding the flow of crystal violet through a 25-mL
      column. When the selected bacteria were analyzed using an inductively coupled
      plasma optical emission spectrometer, high removal rates (99.95 %) of Cd were
      observed following incubation for 48 h. Samples of solids that formed in the
      reaction vessels were examined using a scanning electron microscope. The CdCO3
      compounds primarily showed a spherical shape. The results of this study
      demonstrate that MICP-based sequestration of soluble heavy metals via
      coprecipitation with calcite may be useful for toxic heavy metal bioremediation.

PMID- 24293313
TI  - High-performance electrocatalysts for oxygen reduction derived from cobalt
      porphyrin-based conjugated mesoporous polymers.
AB  - A cobalt-nitrogen-doped porous carbon that exhibits a ribbon-shape morphology,
      high surface area, mesoporous structure, and high nitrogen and cobalt content is
      fabricated for high-performance self-supported oxygen reduction electrocatalytsts
      through template-free pyrolysis of cobalt porphyrin-based conjugated mesoporous
      polymer frameworks. 

PMID- 24293314
TI  - The 'captain of the men of death', Streptococcus pneumoniae, fights oxidative
      stress outside the 'city wall'.

PMID- 24293315
TI  - New targets for old diseases: lessons from mucolipidosis type II.

PMID- 24293316
TI  - Combining chemotherapeutic agents and netrin-1 interference potentiates cancer
      cell death.
AB  - The secreted factor netrin-1 is upregulated in a fraction of human cancers as a
      mechanism to block apoptosis induced by netrin-1 dependence receptors DCC and
      UNC5H. Targeted therapies aiming to trigger tumour cell death via netrin
      1/receptors interaction interference are under preclinical evaluation. We show
      here that Doxorubicin, 5-Fluorouracil, Paclitaxel and Cisplatin treatments
      trigger, in various human cancer cell lines, an increase of netrin-1 expression
      which is accompanied by netrin-1 receptors increase. This netrin-1 upregulation
      which appears to be p53-dependent is a survival mechanism as netrin-1 silencing
      by siRNA is associated with a potentiation of cancer cell death upon Doxorubicin
      treatment. We show that candidate drugs interfering with netrin-1/netrin-1
      receptors interactions potentiate Doxorubicin, Cisplatin or 5-Fluorouracil
      induced cancer cell death in vitro. Moreover, in a model of xenografted nude
      mice, we show that systemic Doxorubicin treatment triggers netrin-1 upregulation
      in the tumour but not in normal organs, enhancing and prolonging tumour growth
      inhibiting effect of a netrin-1 interfering drug. Together these data suggest
      that combining conventional chemotherapies with netrin-1 interference could be a
      promising therapeutic approach. 

PMID- 24293317
TI  - Compound loss of muscleblind-like function in myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is a multi-systemic disease that impacts cardiac and
      skeletal muscle as well as the central nervous system (CNS). DM is unusual
      because it is an RNA-mediated disorder due to the expression of toxic
      microsatellite expansion RNAs that alter the activities of RNA processing
      factors, including the muscleblind-like (MBNL) proteins. While these mutant RNAs
      inhibit MBNL1 splicing activity in heart and skeletal muscles, Mbnl1 knockout
      mice fail to recapitulate the full-range of DM symptoms in these tissues. Here,
      we generate mouse Mbnl compound knockouts to test the hypothesis that Mbnl2
      functionally compensates for Mbnl1 loss. Although Mbnl1(-/-) ; Mbnl2(-/-) double
      knockouts (DKOs) are embryonic lethal, Mbnl1(-/-) ; Mbnl2(+/-) mice are viable
      but develop cardinal features of DM muscle disease including reduced lifespan,
      heart conduction block, severe myotonia and progressive skeletal muscle weakness.
      Mbnl2 protein levels are elevated in Mbnl1(-/-) knockouts where Mbnl2 targets
      Mbnl1-regulated exons. These findings support the hypothesis that compound loss
      of MBNL function is a critical event in DM pathogenesis and provide novel mouse
      models to investigate additional pathways disrupted in this RNA-mediated disease.

PMID- 24293320
TI  - Sphingosine 1-phosphate (S1P) promotes mitochondrial biogenesis in Hep G2 cells
      by activating Peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha).
AB  - Sphingosine 1-phosphate (S1P), a potent bioactive phospholipid, has been reported
      to regulate a broad spectrum of biological processes. However, little is known
      regarding S1P's effects on mitochondrial function. In this study, we investigated
      the S1P's effects on the Peroxisome proliferator-activated receptor gamma
      coactivator 1alpha (PGC-1alpha) signaling pathway and mitochondrial biogenesis in
      Hep G2 cells. Our results indicate that administration of S1P leads to a
      significant upregulation of mitochondrial DNA replication and transcription,
      increased mitochondrial mass, and elevated adenosine triphosphate synthesis. In
      addition, we found that treatment with S1P stimulates expression of PGC-1alpha, a
      master regulator of mitochondrial biogenesis, as well as its downstream targets:
      nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A
      (TFAM). Moreover, our data demonstrate that S1P's effects on PGC-1alpha and
      mitochondrial biogenesis are mediated by the protein kinase A/cAMP response
      element-binding protein (PKA/CREB) pathway. Importantly, we also revealed that
      S1P's effects on mitochondrial biogenesis are dependent on its type 2 receptor
      (S1P2), though not on either its type 1 (S1P1) or type 3 (S1P3) receptors. Based
      on these observations, we concluded that S1P activates the PKA/CREB pathway
      through S1P2, which then promotes expression of PGC-1alpha/NRF1/TFAM and
      subsequent mitochondrial biogenesis in Hep G2 cells. 

PMID- 24293318
TI  - Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell
      differentiation and enhances CNS remyelination.
AB  - The increasing effectiveness of new disease-modifying drugs that suppress disease
      activity in multiple sclerosis has opened up opportunities for regenerative
      medicines that enhance remyelination and potentially slow disease progression.
      Although several new targets for therapeutic enhancement of remyelination have
      emerged, few lend themselves readily to conventional drug development. Here, we
      used transcription profiling to identify mitogen-activated protein kinase (Mapk)
      signalling as an important regulator involved in the differentiation of
      oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue
      culture that activation of Mapk signalling by elevation of intracellular levels
      of cyclic adenosine monophosphate (cAMP) using administration of either dibutyryl
      cAMP or inhibitors of the cAMP-hydrolysing enzyme phosphodiesterase-4 (Pde4)
      enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a
      Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of
      toxin-induced demyelination and a consequent acceleration of remyelination. These
      data reveal a novel approach to therapeutic enhancement of remyelination amenable
      to pharmacological intervention and hence with significant potential for
      translation. 

PMID- 24293321
TI  - Consequences of antagonistic interactions between endophytic fungus and bacterium
      on plant growth and defense responses in Atractylodes lancea.
AB  - Many studies have examined pair-wise interactions between plants and endophytes,
      while overlooking the interplays among multiple endosymbionts and their combined
      impacts on hosts. In this study, Atractylodes lancea plantlets were inoculated
      with endophytic fungus Acremonium strictum AL16, or endophytic bacterium
      Acinetobacter sp., or both, to investigate the impacts of the three-way symbiosis
      on the host. Our results showed that defense-related responses of the co
      inoculated plantlets were delayed and weakened relative to plantlets with single
      inoculants, but no detrimental effects on phyto-physiology (growth,
      photosynthesis) were observed after combined inoculations. Quantitative PCR
      analysis verified a decrease in AL16 colonization density within plants after co
      inoculation with the endobacteria. An in vitro assay was then performed to
      elucidate the suppressed plant defense responses and reduced fungal colonization
      by dual inoculation. The data showed that the presence of Acinetobacter sp.
      reduced AL16 colony diameter and spore germination rate without negatively
      affecting fungal morphology. Additionally, direct hyphal attachment of the
      bacterium to AL16 in vitro was visualized by scanning electronic microscopy.
      Therefore, we propose that a balanced and compatible symbiosis might require
      constraints conferred by the antagonistic endophyte Acinetobacter sp. on the
      fungus AL16 in the tripartite endophytic bacterium-fungus-plant system. 

PMID- 24293322
TI  - Treatment for femoral pseudoaneurysms.
AB  - BACKGROUND: Femoral pseudoaneurysms may complicate up to 8% of vascular
      interventional procedures. Small pseudoaneurysms can spontaneously clot, but
      sometimes definitive treatment is needed. Surgery has traditionally been
      considered the 'gold standard' treatment, although it is not without risk in
      patients with severe cardiovascular disease. Less invasive treatment options such
      as Duplex ultrasound-guided compression and percutaneous thrombin injection are
      available, however, evidence of their efficacy is limited. This is an update of a
      Cochrane review first published in 2006. OBJECTIVES: To assess the effects of
      different treatments for femoral pseudoaneurysms resulting from endovascular
      procedures, specifically assessing less invasive treatment options such as blind
      manual or mechanical compression, ultrasound-guided compression, or percutaneous
      thrombin injection. SEARCH METHODS: For this update the Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator searched the Specialised
      Register (last searched October 2013) and CENTRAL (2013, Issue 9). SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing two treatments for
      femoral pseudoaneurysms following vascular interventional procedures were
      considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Four
      studies were included in the analyses comparing: manual compression versus
      ultrasound-guided compression; ultrasound-guided application of a mechanical
      device (FemoStop) versus blind application; and ultrasound-guided compression
      versus percutaneous thrombin injection (two studies). There were no studies with
      a surgical intervention arm. Data were extracted independently by both authors.
      MAIN RESULTS: Compression (manual or FemoStop) was effective in achieving
      pseudoaneurysm thrombosis although ultrasound-guided application failed to confer
      any benefit (risk ratio (RR) 0.96; 95% confidence interval (CI) 0.88 to
      1.04).Percutaneous thrombin injection was more effective than a single session of
      ultrasound-guided compression in achieving primary pseudoaneurysm thrombosis
      within individual RCTs but merged data failed to show statistical significance
      (RR 2.81; 95% CI 0.44 to 18.13). There was no statistically significant
      difference in the length of hospital stay between the two groups and no
      complications were reported apart from one deep vein thrombosis in the
      compression group. AUTHORS' CONCLUSIONS: The limited evidence base appears to
      support the use of thrombin injection as an effective treatment for femoral
      pseudoaneurysm. A pragmatic approach may be to use compression (blind or
      ultrasound-guided) as first-line treatment, reserving thrombin injection for
      those in whom the compression procedure fails.

PMID- 24293323
TI  - A host deficiency of discoidin domain receptor 2 (DDR2) inhibits both tumour
      angiogenesis and metastasis.
AB  - Discoidin domain receptor 2 (DDR2) is a unique receptor tyrosine kinase (RTK)
      that signals in response to collagen binding and is implicated in tumour
      malignant phenotypes such as invasion and metastasis. Although it has been
      reported that DDR2 expression is up-regulated in activated endothelial cells
      (ECs), functional studies are lacking. Herein, we found that enforced expression
      of DDR2 promoted proliferation, migration and tube formation of primary human
      umbilical vein endothelial cells (HUVECs). The results of immunohistochemical
      analysis showed a strikingly high level of DDR2 in human tumour ECs. Most
      significantly, we discovered that a host deficiency of DDR2 inhibits subcutaneous
      angiogenesis induced by either VEGF or tumour cells. In addition, the remaining
      tumour vessels in DDR2-deficient mice exhibit some normalized properties. These
      vascular phenotypes are accompanied by the up-regulation of anti-angiogenic genes
      and down-regulation of pro-angiogenic genes, as well as by alleviated tumour
      hypoxia. By use of a tail vein metastasis model of melanoma, we uncovered that
      loss of stromal DDR2 also suppresses tumour metastasis to the lung. Hence, our
      current data disclose a new mechanism by which DDR2 affects tumour progression,
      and may strengthen the feasibility of targeting DDR2 as an anticancer strategy.

PMID- 24293324
TI  - Physiological and oxidative stress biomarkers in the freshwater monosex Nile
      tilapia, Oreochromis niloticus L., exposed to pendimethalin-based herbicide.
AB  - Fish are relatively sensitive to changes in their surrounding environment,
      including increasing pollution. Therefore, the present study was undertaken to
      evaluate the impact of contamination with the pendimethalin-based herbicide;
      Stomp((r)) 50% EC (50% pendimethalin as emulsive concentrate) on adults of the
      monosex Nile tilapia Oreochromis niloticus L. A total of 260 fish with body
      weights of 90 +/- 5.0 g were used in the determination of the 96-h LC50 value and
      of the impacts of acute exposure to pendimethalin on physiological parameters,
      and oxidative stress and antioxidant biomarkers. The 96-h median lethal
      concentration (96-h LC50 ) value of pendimethalin for monosex Nile tilapia was
      determined as 4.92 mg/L. Abnormal behavioral responses of the fish and the toxic
      symptoms of pendimethalin exposure are described. Acute exposure to pendimethalin
      induced leukocytosis, hyperglobulinemia, and hyperglycemia, but resulted in
      nonsignificant changes in other hemato-biochemical parameters. Moreover,
      pendimethalin increased lipid peroxidation (LPO) and decreased levels of reduced
      glutathione and antioxidant enzymes; superoxide dismutase, catalase, and
      glutathione reductase in both liver and gill tissues, in a time-dependent manner,
      with maximum alterations observed in the gills rather than the liver. We conclude
      that although pendimethalin is moderately toxic, it does not cause hepatorenal
      toxicity. However, this herbicide pollutant induces major disturbances to the
      antioxidant system; induction of oxidative stress and LPO is the proposed
      toxicodynamic pathway for such stress.

PMID- 24293325
TI  - The basis for rootstock resilient to Capnodis species: screening for genes
      encoding delta-endotoxins from Bacillus thuringiensis.
AB  - BACKGROUND: Conventional methods often fail to control the flatheaded borers
      Capnodis spp., major pests of stone fruit trees; the larvae are protected from
      insecticides and predation because they feed deep in the roots. A potential
      solution is transgenic trees producing in their roots toxic compounds such as Cry
      proteins of Bacillus thuringiensis (Bt). RESULTS: Toxicities against Capnodis
      larvae were demonstrated by exploiting a recently designed artificial larval diet
      and an available collection of field isolated Bt. An isolate of Bt tenebrionis
      (Btt) from commercial bioinsecticide (Novodor) displayed LC50 and LC95 values of
      3.2 and 164 mg g(-1) , respectively, against neonates of Capnodis tenebrionis,
      whereas values of the most toxic field isolate K-7 were 1.9 and 25.6 mg g(-1)
      respectively. Weights of surviving larvae after 1 month on diets containing low
      concentrations of K-7 (0.1-1.0 mg g(-1) ) were lower than on Btt or untreated
      larvae. K-7 was also toxic against larvae of C. cariosa and C. miliaris and found
      to harbour genes encoding Cry9Ea-like and Cry23Aa/Cry37Aa binary toxins.
      CONCLUSION: Larvae of Capnodis spp. are susceptible to Bt Cry toxins. Expressing
      cry genes active against these pests thus seems a feasible solution towards
      production of transgenic rootstock trees resilient to the pest.

PMID- 24293326
TI  - Does the type of fluid affect rapidity of shock reversal in an anaesthetized
      piglet model of near-fatal controlled haemorrhage? A randomized study.
AB  - BACKGROUND: The optimal resuscitation fluid for the early treatment of severe
      bleeding patients remains highly debated. The objective of this experimental
      study was to compare the rapidity of shock reversal with lactated Ringer (LR) or
      hydroxyethyl starch (HES) 130/0.4 at the early phase of controlled haemorrhagic
      shock. To assess the influence of vascular permeability in this model, we
      measured plasma vascular endothelial growth factor (VEGF) levels during the
      experiment. METHODS: Thirty-six anaesthetized and mechanically ventilated piglets
      were bled (<30 ml kg(-1)) to hold mean arterial pressure (MAP) at 40 mm Hg for
      more than 30 min and were resuscitated in two randomized groups: LR (n=14) or HES
      (n=14) at 1 ml kg(-1) min(-1) until MAP reached its baseline value of +/-10%. MAP
      was maintained at its baseline value for 1 h. The time and fluid volume necessary
      to restore the baseline MAP value were measured. RESULTS: The time to restore the
      baseline MAP value of +/-10% was significantly lower in the HES group (P<0.001).
      During the initial resuscitation phase, the infused volume was 279 (119) ml in
      the HES group and 1011 (561) ml in the LR group (P<0.0001). During the
      stabilization phase, the infused volume was 119 (124) ml in the HES group and 541
      (506) ml in the LR group. Biological data and plasma VEGF levels were similar
      between the groups. CONCLUSIONS: Restoration of MAP was four times faster with
      HES than with LR in the early phase of controlled haemorrhagic shock. However,
      there was no evidence of increased vascular permeability.

PMID- 24293327
TI  - Intracranial pressure monitoring, cerebral perfusion pressure estimation, and
      ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?
AB  - Measurement of intracranial pressure (ICP) and mean arterial pressure (MAP) is
      used to derive cerebral perfusion pressure (CPP) and to guide targeted therapy of
      acute brain injury (ABI) during neurointensive care. Here we provide a narrative
      review of the evidence for ICP monitoring, CPP estimation, and ICP/CPP-guided
      therapy after ABI. Despite its widespread use, there is currently no class I
      evidence that ICP/CPP-guided therapy for any cerebral pathology improves
      outcomes; indeed some evidence suggests that it makes no difference, and some
      that it may worsen outcomes. Similarly, no class I evidence can currently advise
      the ideal CPP for any form of ABI. 'Optimal' CPP is likely patient-, time-, and
      pathology-specific. Further, CPP estimation requires correct referencing (at the
      level of the foramen of Monro as opposed to the level of the heart) for MAP
      measurement to avoid CPP over-estimation and adverse patient outcomes. Evidence
      is emerging for the role of other monitors of cerebral well-being that enable the
      clinician to employ an individualized multimodality monitoring approach in
      patients with ABI, and these are briefly reviewed. While acknowledging
      difficulties in conducting robust prospective randomized studies in this area,
      such high-quality evidence for the utility of ICP/CPP-directed therapy in ABI is
      urgently required. So, too, is the wider adoption of multimodality
      neuromonitoring to guide optimal management of ICP and CPP, and a greater
      understanding of the underlying pathophysiology of the different forms of ABI and
      what exactly the different monitoring tools used actually represent. 

PMID- 24293328
TI  - Appropriateness of referrals to a tertiary referral centre for bone mineral
      density testing.
AB  - INTRODUCTION: Evidence-based guidelines for who should have a dual-energy X-ray
      absorptiometry (DXA) scan are well established. Much attention has been
      appropriately focussed on increasing the proportion of persons at high risk for
      fracture who are being referred for such investigation. Little literature exists
      on the extent of inappropriate referrals for DXA. In this cross-sectional study
      we assessed the prevalence of inappropriate referrals for DXA studies at our
      centre using modified International Society for Clinical Densitometry (ISCD)
      guidelines. METHODS: All DXA referrals were vetted for appropriateness and
      priority using established ISCD criteria. We evaluated the reasons for DXA
      referral on all subjects and studied the prevalence of missing information, and
      the number of referrals for DXA deemed to be inappropriate at our institution.
      RESULTS: Two thousand and twenty-five DXA referrals were reviewed. Information
      was missing on many requests (e.g., menopausal status, body mass index), and 33 %
      of the referrals were deemed as inappropriate. Compared to those deemed
      appropriate, inappropriate referrals were more likely to be younger females, had
      no risk factors for osteoporosis, had an inappropriate referral reason, and had
      less/missing information. CONCLUSIONS: In this study we have noted a concerning
      number of DXA referrals with limited information or no appropriate indication for
      such an examination. Education of referring physicians should focus on not only
      improving referrals for subjects at high risk, but also inappropriate referrals
      for subjects at low risk.

PMID- 24293329
TI  - Meeting report - Arf and Rab family G proteins.
AB  - A FASEB Summer Research Conference entitled 'Arf and Rab family G proteins' was
      held in July 2013 at Snowmass Village, Snowmass, Colorado. Arfs and Rabs are two
      families of GTPases that control membrane trafficking in eukaryotic cells, and
      increasing evidence indicates that their functions are tightly coordinated.
      Because many workers in this field have focused on only one family, this meeting
      was designed to integrate our understanding of the two families. The conference
      was organized by Elizabeth Sztul (University of Alabama, Birmingham, USA) and Jim
      Casanova (University of Virginia, Charlottesville, USA), and provided an
      opportunity for approximately 90 scientists to communicate their work and discuss
      future directions for the field. The talks highlighted the structural, functional
      and regulatory properties of Arf and Rab GTPases and the need to develop
      coordinated approaches to investigate them. Here, we present the major themes
      that emerged from the meeting.

PMID- 24293330
TI  - Misregulation of autophagy and protein degradation systems in myopathies and
      muscular dystrophies.
AB  - A number of recent studies have highlighted the importance of autophagy and the
      ubiquitin-proteasome in the pathogenesis of muscle wasting in different types of
      inherited muscle disorders. Autophagy is crucial for the removal of dysfunctional
      organelles and protein aggregates, whereas the ubiquitin-proteasome is important
      for the quality control of proteins. Post-mitotic tissues, such as skeletal
      muscle, are particularly susceptible to aged or dysfunctional organelles and
      aggregation-prone proteins. Therefore, these degradation systems need to be
      carefully regulated in muscles. Indeed, excessive or defective activity of the
      autophagy lysosome or ubiquitin-proteasome leads to detrimental effects on muscle
      homeostasis. A growing number of studies link abnormalities in the regulation of
      these two pathways to myofiber degeneration and muscle weakness. Understanding
      the pathogenic role of these degradative systems in each inherited muscle
      disorder might provide novel therapeutic targets to counteract muscle wasting. In
      this Commentary, we will discuss the current view on the role of autophagy
      lysosome and ubiquitin-proteasome in the pathogenesis of myopathies and muscular
      dystrophies, and how alteration of these degradative systems contribute to muscle
      wasting in inherited muscle disorders. We will also discuss how modulating
      autophagy and proteasome might represent a promising strategy for counteracting
      muscle loss in different diseases. 

PMID- 24293331
TI  - A new age of regenerative medicine: fusion of tissue engineering and stem cell
      research.

PMID- 24293332
TI  - Assessing the impact of multi-compartment compliance aids on clinical outcomes in
      the elderly: a pilot study.
AB  - BACKGROUND: Medication non-adherence is a major problem for elderly people.
      Multicompartment compliance aids (MCAs) have been advocated as a solution for
      this problem. OBJECTIVE: To assess the impact of using MCAs in self-reported
      adherence and clinical biomarkers of elderly patients followed in a community
      pharmacy. SETTING: One community pharmacy at Sabugal (Portugal). METHODS: A four
      month prospective, non-randomised, controlled study was performed. Autonomous
      patients aged 65 or more using 3 or more medicines and under follow-up in the
      pharmacy were invited to participate. All patients were offered to receive their
      medication in MCAs prepared in the pharmacy. Patients refusing the MCA were used
      as control. The intervention consisted of providing 4 weekly MCAs during the
      monthly visit. All patients received regular pharmacy counselling. Blood pressure
      (BP), lipid profile and glycaemia were assessed at baseline and monthly for all
      the patients. Morisky self-reported scale was applied at baseline and at the end
      of the study. Bivariate analysis and generalized estimation equations (GEE) were
      used. MAIN OUTCOME MEASURE: Self-reported medication adherence, clinical
      biomarkers: BP, lipid profile, glycaemia. RESULTS: 54 patients between 65 and 90
      years were under follow-up. 44 patients accepted the MCA, constituting the
      intervention group. No difference in the baseline biomarkers between both groups
      was found. The bivariate pre-post analysis yielded significant improvements in
      the intervention groups, but not in the control, for glycaemia (p < 0.001), HDL-c
      (p = 0.018), and systolic (p < 0.001) and diastolic (p = 0.012) BP. However, when
      introducing the 'time in follow-up' in the GEE model, all the differences became
      non-significant, except systolic BP, but the time remained significant for all
      the biomarkers. CONCLUSION: MCAs apparently improve several clinical biomarkers
      in a cohort of patients under pharmacist's follow-up. When including the time in
      pharmacist's followup in a GEE, the effect of the MCA disappeared, remaining only
      the time as a significant variable. Not considering the time in follow-up may be
      overestimating the effect of MCAs.

PMID- 24293333
TI  - Adherence to inhaled corticosteroids by asthmatic patients: measurement and
      modelling.
AB  - BACKGROUND: Poor adherence to inhaled corticosteroids (ICS) is known as the main
      cause for therapeutic failure in asthma treatment and associated morbidity. To
      improve adherence, targetted and effective interventions need to be developed
      ideally based on using longitudinal follow-up of a large study cohort to
      establish patterns and influences on adherence. OBJECTIVE: To develop an annual
      measure of asthma patients' adherence to ICS using primary care prescribing data
      over consecutive annual intervals, and to statistically model ICS adherence
      controlling for a range of patient factors. SETTING: A retrospective cohort study
      between 1997 and 2010 using United Kingdom general practice prescribing data on
      asthma patients aged between 12 and 65 years, without a diagnosis of chronic
      obstructive pulmonary disease. METHOD: Patient's ICS prescriptions are used to
      calculate the 'number of days prescribed during calendar year' divided by 'number
      of days in the interval' to form an annual prescription possession ratio (PPR)
      for each patient. Several definitions of PPR are considered and compared when
      calculating numerator and denominator. Adherence, measured by the preferred PPR,
      is then modelled to estimate the effect of asthma exacerbation, severity, control
      and other patient factors on adherence. MAIN OUTCOME MEASURE: PPR, being a proxy
      measure for adherence. RESULTS: Annual PPR by all strategies gave a similar
      frequency profile. ICS were either over- or under-prescribed for over half of the
      follow-up time. Adherence was lower in younger patients, those newer to the study
      timeframe, those with less severe asthma, those with good control, with lower
      previous adherence, and who had not previously experienced an exacerbation.
      CONCLUSION: The chosen PPR simulated clinical use of ICS most closely; including
      overlapping days, excess days passed to the next interval, considering gaps in
      the denominator, with censoring at 100 %. The PPR is a useful measure for
      signalling or measuring adherence changes over time. The modelling results
      identified many characteristics which would indicate which asthma patients and at
      what points in their treatment cycle they would be at increased risk of low
      adherence.

PMID- 24293334
TI  - Look alike/sound alike drugs: a literature review on causes and solutions.
AB  - BACKGROUND: The implementation of preventive measures of look-alike/sound-alike
      drugs incidents has given rise to a fundamental rule in Clinical Risk Management,
      but the problem is underestimated, endorsed by the absence or inadequate presence
      of specific uniformed procedures. In literature, there are few reviews about look
      alike/sound-alike drugs. AIM OF THE REVIEW: To collect and summarize best
      practice and significant technological solutions proposed by different
      disciplines involved in look-alike/soundalike drugs limiting solution research.
      METHOD: A PubMed (any date) and EMBASE (all years) search was conducted in
      January 2013 with look alike sound alike drug [look AND (sound/exp OR sound) AND
      alike AND (drug/exp OR drug)] as search term. Later, references were selected
      focusing on lookalike/sound-alike drugs original research describing incident,
      identifying health operator difficulty, testing any type of intervention against
      errors, reporting a qualitative or quantitative description of the look
      alike/sound-alike drugs errors. RESULTS: Forty and ninety-four articles were
      identified by a PubMed and Embase search respectively, with search term and
      limits described above. Later, articles not respecting selection criteria or
      overlapping were eliminated. In the end, 14 references were considered, 10 being
      from PubMed and 4 from Embase. CONCLUSION: Results show and confirm the
      multidisciplinary interest of the research on look-alike/sound-alike drugs, and
      the difficulty to perform systematic review or metaanalysis for many clinical
      questions that have great relevance. This review has identified technology and
      management solutions that could effectively limit, or eliminate, look-alike/sound
      alike drugs errors in hospital wards, or outside the hospital where the risk is
      more uncontrollable: however look-alike/sound-alike drugs therapy errors are not
      supported by reliable statistics but events reported in the literature can not be
      underestimated.

PMID- 24293335
TI  - Pharmacist-led intervention study to improve drug therapy in asthma and COPD
      patients.
AB  - BACKGROUND: Pharmacists can play an important role in identifying and instructing
      pulmonary patients on their inhalation techniques in their patient contacts when
      dispensing inhalation medication. Pharmacy dispensing data can be used to
      identify inappropriate drug use in asthma and chronic obstructive pulmonary
      disease (COPD) patients. Recent studies found beneficial effects of pharmacy care
      services in improving drug adherence of pulmonary patients. However, large-scale
      and rigorous evaluations on pharmacist-led interventions in community care
      settings to enhance evidence-based drug treatment in patients with asthma and
      COPD seems to be lacking and results from studies on pharmacist-led interventions
      for pharmacotherapy improvements are inconsistent. This study evaluated the
      effectiveness of pharmacist-led interventions on suboptimal drug use patterns
      with asthma or COPD medication with substantial numbers of pharmacies and
      patients involved. SETTING: A prospective cohort study in a group of community
      pharmacies (intervention group) with a matched control group of Dutch community
      pharmacies was conducted between May 2011 and February 2012. Algorithms on 19
      potential problems with asthma or COPD medication in a national dispensing
      database were used to signal patients to pharmacists of the intervention group
      (IG). METHODS: IG pharmacists selected patients for comprehensive care by a
      structured program. Changes in problems were measured during 10 months in
      selected and all users of asthma and COPD medication of IG pharmacies and in
      compared to a control pharmacies (CG) without the structured program. Primary
      outcome was reduction of oral high dosage corticosteroids or antibiotics (HDT).
      Secondary outcomes were changes in the persistence of 19 potential problems in
      the IG compared to CG. RESULTS: In the 107 IG pharmacies, 3,757 patients were
      selected for comprehensive care from totally 102,497 asthma or COPD patients and
      compared with 105,507 patients from 105 CG pharmacies. The mean number of HDT
      decreased in selected IG patients by an additional 0.54 (95 % CI 0.21-0.86) HDT
      treatments. From the problems with specific COPD and asthma medication, all
      problems decreased additionally to the CG within the total asthma or COPD
      population from the IG. Within the selected IG population the following problems
      decreased additionally for obsolete medication by 35 % (95 % CI 6-54 %), contra
      indicated medication by 61 % (95 % CI 38-75 %) and lower use of powder inhalers
      in elderly patients by 29 % (95 % CI 13-42 %). CONCLUSION: Community pharmacists
      actively providing comprehensive pharmacy care could improve effective treatment
      in asthma and COPD patients and thereby decrease the number of prescriptions for
      exacerbations for these patients.

PMID- 24293336
TI  - Correlation between the use of 'over-the-counter' medicines and adherence in
      elderly patients on multiple medications.
AB  - BACKGROUND: Medication adherence is a multifaceted issue that is influenced by
      various factors. One factor may be the concurrent use of over-the-counter
      (OTC)medicines. The use of OTC medicine has been reported as common amongst
      elderly patients. OBJECTIVE: To determine if a correlation exists between the use
      of OTC medicines and adherence to prescribed medications in elderly patients.
      SETTING: Non-institutionalised elderly patients in Denmark. METHODS: Elderly
      unassisted patients aged >=65 prescribed five or more prescription drugs were
      included in the study. Information on the use of concurrent OTC medications
      (herbal medicines, dietary supplements, or non-prescribed drugs) was elicited
      during home visit interviews. Prescription drug adherence was determined by pill
      counts. A patient was categorised as non-adherent if the me an adherence rate for
      all drugs consumed was?80 %. Different sensitivity analyses were made where
      adherence was defined different. MAIN OUTCOME MEASURE: Medication adherence based
      on pill-count. RESULTS: A total of 253 participants included 72 % who used OTC
      medicines and 11 % who did not adhere to their prescriptions. Users of OTC
      medicines, however, were significantly more likely to be adherent than were non
      users (odds ratio 0.41; 95 %confidence interval 0.18-0.91). Sensitivity analyses
      where adherence was defined different show no relationship between adherence and
      use of OTC medicine. Furthermore,separate analyses of herbal medicines, dietary
      supplements,or non-prescribed drugs did not correlate with adherence to
      prescriptions. CONCLUSION: Amongst elderly patients on multiple medications a
      positive relationship was found between the overall use of OTC medicines and
      adherence to prescription drugs, in contrast to none when adherence were defined
      different or herbal medicines, dietary supplements, or non-prescribed drugs were
      analysed separately.

PMID- 24293337
TI  - Investigating the association between health literacy and non-adherence.
AB  - BACKGROUND: Low health literacy is expected to be associated with medication non
      adherence and early research indicated that this might be the case. Further
      research suggested that the relationship may be more equivocal. AIM OF THE
      REVIEW: The goal of this paper is initially to clarify whether there is a clear
      relationship between health literacy and non-adherence. Additionally, this review
      aims to identify factors that may influence that relationship and ultimately to
      better understand the mechanisms that may be at work in the relationship. METHOD:
      English language original research or published reviews of health literacy and
      non-adherence to orally administered medications in adults were identified
      through a search of four bibliographic databases (PubMed, EMBASE, CINAHL, and
      EBSCO Health). RESULTS: The search protocol produced 78 potentially relevant
      articles, of which 16 articles addressed factors that contribute to non-adherence
      and 24 articles reported on the results of research into the relationship between
      non-adherence and health literacy. Factors that contribute to non-adherence can
      be categorised into patient related factors, including patient beliefs;
      medication related factors; logistical factors; and factors around the patient
      provider relationship. Of the 23 original research articles that investigated the
      relationship between non-adherence and health literacy, only five reported
      finding clear evidence of a relationship, four reported mixed results and 15
      articles reported not finding the expected relationship. Research on possible
      mechanisms relating health literacy to non-adherence suggest that disease and
      medication knowledge are not sufficient for addressing non-adherence while self
      efficacy is an important factor. Other findings suggest a possible U-shaped
      relationship between non-adherence and health literacy where people with low
      health literacy are more often non-adherent, largely unintentionally; people with
      moderate health literacy are most adherent; and people with high health literacy
      are somewhat non-adherent, sometimes due to intentional non-adherence.
      CONCLUSION: It is clear that relevant research generally fails to find a
      significant relationship between non-adherence and health literacy. A U-shaped
      relationship between these two conditions would explain why linear statistical
      tests fail to identify a relationship across all three levels of health literacy.
      It can also account for the conditions under which both positive and negative
      relationships may be found.

PMID- 24293338
TI  - The Aston Medication Adherence Study: mapping the adherence patterns of an inner
      city population.
AB  - BACKGROUND: The Aston Medication Adherence Study was designed to examine non
      adherence to prescribed medicines within an inner-city population using general
      practice (GP) prescribing data. OBJECTIVE: To examine non-adherence patterns to
      prescribed oral medications within three chronic disease states and to compare
      differences in adherence levels between various patient groups to assist the
      routine identification of low adherence amongst patients within the Heart of
      Birmingham teaching Primary Care Trust (HoBtPCT). SETTING: Patients within the
      area covered by HoBtPCT (England) prescribed medication for dyslipidaemia, type-2
      diabetes and hypothyroidism, between 2000 and 2010 inclusively. HoBtPCT's
      population was disproportionately young, with seventy per cent of residents from
      Black and Minority Ethnic groups. METHOD: Systematic computational analysis of
      all medication issue data from 76 GP surgeries dichotomised patients into two
      groups (adherent and non-adherent) for each pharmacotherapeutic agent within the
      treatment groups. Dichotomised groupings were further analysed by recorded
      patient demographics to identify predictors of lower adherence levels. Results
      were compared to an analysis of a self-report measure of adherence [using the
      Modified Morisky Scale((c)) (MMAS-8)] and clinical value data (cholesterol
      values) from GP surgery records. MAIN OUTCOME: Adherence levels for different
      patient demographics, for patients within specific longterm treatment groups.
      RESULTS: Analysis within all three groups showed that for patients with the
      following characteristics, adherence levels were statistically lower than for
      others; patients: younger than 60 years of age; whose religion is coded as
      "Islam"; whose ethnicity is coded as one of the Asian groupings or as
      "Caribbean", "Other Black" and "African"; whose primary language is coded as
      "Urdu" or "Bengali"; and whose postcodes indicate that they live within the most
      socioeconomically deprived areas of HoBtPCT. Statistically significant
      correlations between adherence status and results from the selfreport measure of
      adherence and of clinical value data analysis were found. CONCLUSION: Using data
      from GP prescribing systems, a computerised tool to calculate individual
      adherence levels for oral pharmacotherapy for the treatment of diabetes,
      dyslipidaemia and hypothyroidism has been developed. The tool has been used to
      establish nonadherence levels within the three treatment groups and the
      demographic characteristics indicative of lower adherence levels, which in turn
      will enable the targeting of interventional support within HoBtPCT.

PMID- 24293339
TI  - Impact of pharmaceutical care on adherence, hospitalisations and mortality in
      elderly patients.
AB  - BACKGROUND: Elderly polypharmacy patients may be more at risk of not adhering to
      medication. If so, the underlying reasons may be more readily disclosed during
      private discussions with patients. Hence pharmaceutical care discussions at home
      might improve treatment adherence. OBJECTIVE: The aim of this study was to
      investigate the impact of pharmaceutical care on medication adherence,
      hospitalisation and mortality in elderly patients prescribed polypharmacy.
      SETTING: Pharmaceutical care discussed at home. METHODS: A randomised controlled
      trial with two arms; pharmaceutical care (n = 315) and controls (n = 315) was
      designed. It involved patients aged 65+ years living in Aarhus, Denmark who used
      five drugs or more without assistance. Pharmacists visited the pharmaceuticalcare
      patients at home, once only, and followed them during the subsequent year with
      three telephone calls. Non-adherence was measured by a pill-count. Patients were
      categorised as non-adherent if their mean adherence rate for all drugs consumed
      was <80 %. The impact of pharmaceutical care on non-adherence and hospitalisation
      was analysed by 2 * 2 tables, and mortality by Cox regression. MAIN OUTCOME
      MEASURE: Medication adherence, hospitalisation and mortality. RESULTS: The final
      analyses included 517 patients (median age 74 years; females 52 %). Dropouts were
      more frequent for the pharmaceutical-care group than for controls. Pharmacists
      encountered drug-related problems amongst 72 % of pharmaceutical-care patients.
      Pharmaceutical-care patients (11 %) and control patients (10 %) were similarly
      nonadherent (Odds ratio 1.14; 95 % confidence interval 0.65-2.00), and similar
      with respect to hospitalisation frequency (30 vs. 28 %; Odds ratio 1.14; 95 %
      confidence interval 0.78-1.67) and mortality (7.5 vs. 5 %; Hazard ratio 1.41; 95
      % confidence interval 0.71-2.82). CONCLUSIONS: Pharmaceutical care given to our
      elderly polypharmacy patients made no significant impact on medication adherence,
      hospitalisation or mortality, when compared to comparable control patients.

PMID- 24293340
TI  - Differential expression of serum/plasma proteins in various infectious diseases:
      specific or nonspecific signatures.
AB  - Apart from direct detection of the infecting organisms or biomarker of the
      pathogen itself, surrogate host markers are also useful for sensitive and early
      diagnosis of pathogenic infections. Early detection of pathogenic infections,
      discrimination among closely related diseases with overlapping clinical
      manifestations, and monitoring of disease progression can be achieved by
      analyzing blood biomarkers. Therefore, over the last decade large numbers of
      proteomics studies have been conducted to identify differentially expressed human
      serum/plasma proteins in different infectious diseases with the intent of
      discovering novel potential diagnostic/prognostic biomarkers. However, in-depth
      review of the literature indicates that many reported biomarkers are altered in
      the same way in multiple infectious diseases, regardless of the type of
      infection. This might be a consequence of generic acute phase reactions, while
      the uniquely modulated candidates in different pathogenic infections could be
      indicators of some specific responses. In this review article, we will provide a
      comprehensive analysis of differentially expressed serum/plasma proteins in
      various infectious diseases and categorize the protein markers associated with
      generic or specific responses. The challenges associated with the discovery,
      validation, and translational phases of serum/plasma biomarker establishment are
      also discussed. 

PMID- 24293341
TI  - Effect of the fibrillar microstructure on the efficiency of high molecular weight
      diketopyrrolopyrrole-based polymer solar cells.
AB  - The nature of the solubilizing alkyl side chains has a strong effect on the
      performance of semiconducting diketopyrrolopyrrole polymers in organic solar
      cells with fullerene acceptors. The effect relates to the width of
      semicrystalline polymer fibrils that form in these blends. If the width of the
      fibril is wider than the exciton diffusion length, fewer charges form and the
      efficiency drops. 

PMID- 24293342
TI  - Developing a novel method to analyse Gafchromic EBT2 films in intensity modulated
      radiation therapy quality assurance.
AB  - Recently individual intensity modulated radiation therapy quality assurances
      (IMRT QA) have been more and more performed with GafchromicTM EBT series films
      processed in red-green-blue (R-G-B) channel due to their extremely high spatial
      resolution. However, the efficiency of this method is relatively low, as for each
      box of film, a calibration curve must be established prior to the film being used
      for measurement. In this study, the authors find a novel method to process the
      GafchromicTM EBT series, that is, to use the 16-bit greyscale channel to process
      the exposed film rather than the conventional 48-bit R-G-B channel, which greatly
      increases the efficiency and even accuracy of the whole IMRT procedure. The main
      advantage is that when processed in greyscale channel, the GafchromicTM EBT2
      films exhibits a linear relationship between the net pixel value and the dose
      delivered. This linear relationship firstly reduces the error in calibration
      curve fitting, and secondly saves the need of establishing a calibration curve
      for each box of films if it is only to be used for relative measurements.
      Clinical testing for this novel method was carried out in two radiation therapy
      centres that involved a total of 743 IMRT cases, and 740 cases passed the 3 mm 3
      % gamma analysis criteria. The cases were also tested with small ionization
      chambers (cc-13) and the results were convincing. Consequently the authors
      recommend the use of this novel method to improve the accuracy and efficiency of
      individual IMRT QA procedure using Gafchromic EBT2 films.

PMID- 24293343
TI  - Isolation and characterization of dissolved organic matter fractions from
      antialgal products of Microcystis aeruginosa.
AB  - An antialgal bacterium, Streptomyces sp. HJC-D1, was applied for the
      biodegradation of cyanobacterium Microcystis aeruginosa, and the isolation and
      characterization of dissolved organic matter (DOM) fractions in antialgal
      products were studied. Results showed the the growth of M. aeruginosa was
      significantly inhibited by the cell-free filtrate of Streptomyces sp. HJC-D1 with
      the growth inhibition of 86 +/- 7 %. The antialgal products were divided using
      resin adsorbents into the hydrophilic fraction (HPI), hydrophobic acid (HPO-A),
      transphilic acid (TPI-A), hydrophobic neutral and transphilic neutral, and then
      the five fractions were analyzed by the 3-D fluorescence spectroscopy, gel
      permeation chromatography, and Fourier transform infrared spectroscopy. The
      results indicated that the HPI component was the most abundant DOM fraction in
      the antialgal products, and its concentration was increased with the increase of
      cell-free filtrate concentration. The fluorescence peak location and intensity
      analysis showed that the protein-, fulvic-, and humic-like substances were
      dominant in the HPI, HPO-A, and TPI-A fractions, and intensities of the relevant
      fluorescence peaks were stronger in the experimental groups than those of the
      control groups. It was also found that the number-average molecular weight of DOM
      fractions ranged from 245 to 1,452 g mol(-1), and thereinto organic acids such as
      HPO-A and TPI-A exhibited lower molecular weights.

PMID- 24293344
TI  - Letter to the editor concerning Tsuchiya K et al. "Dosimetric comparison between
      intensity-modulated radiotherapy and standard wedged tangential technique for
      whole-breast radiotherapy in Asian women with relatively small breast volumes".

PMID- 24293345
TI  - New diphtheria toxin repressor types depicted in a Romanian collection of
      Corynebacterium diphtheriae isolates.
AB  - Corynebacterium diphtheriae is the etiological agent of diphtheria, a potential
      fatal disease caused by a corynephage toxin. The expression of this diphtheria
      toxin is controlled via an iron-dependent repressor with various functions
      (DtxR). Some mutations in the dtxR gene are associated with diminished activity
      or even with total loss of DtxR function. We conducted a molecular study to
      characterize the dtxR alleles harbored by 34 isolates of C. diphtheriae recovered
      from Romanian patients between 1961 and 2007. Three of the seven alleles
      identified in this study have not previously been described. Two new DtxR types
      were identified, one of which has an unusual polypeptide length. All the new DtxR
      types were found in toxigenic isolates, suggesting that they effectively regulate
      the expression of diphtheria toxin. Furthermore, one of the new DtxR identified
      was also found in a non-toxigenic isolate, making it a potential source of
      toxigenic isolates after lysogenic conversion.

PMID- 24293346
TI  - Novel therapies for treating familial hypercholesterolemia.
AB  - Familial hypercholesterolemia is an inherited disorder associated with early
      accelerated atherosclerosis with morbidity and mortality resulting from premature
      cardiovascular disease. Affected individuals have extreme elevations in low
      density lipoprotein cholesterol levels. Patients usually do not achieve target
      reductions in cholesterol levels with conventional antihyperlipidemic
      pharmacotherapy. This unmet need has resulted in the recent development and
      approval of novel therapies targeting different cholesterol pathways. This
      article briefly summarizes familial hypercholesterolemia and then discusses the
      newer pharmacotherapies available in the management of familial
      hypercholesterolemia. 

PMID- 24293347
TI  - Genetics and personalized medicine--a role in statin therapy?
AB  - Pharmacogenetics uses the genetic variation in metabolic pathways to identify
      groups of patients who may respond differently in terms of therapeutic and
      adverse effects. Much clinical interest lies in drug metabolism and the
      opportunity to improve prescribing efficacy and safety. Owing to widespread use
      and increasing concern regarding side effects, statins are of significant
      interest in this area. Among other benefits, statins have been shown to improve
      lipid profiles and reduce coronary heart disease event rates in many populations.
      However, variability in drug response exists, and genetic variability may be a
      contributing factor. Our primary goal is to feature the most important genes
      involved in lipid metabolism, clinical outcomes, and statin-induced side effects,
      highlighting genome-wide association studies and the candidate gene approach. 

PMID- 24293349
TI  - Mandating advance directives.
AB  - As the population ages, end-of-life care (EOLC) costs become an increasingly
      pressing subject. Advance directives (ADs) are legal documents that allow
      individuals to convey their decisions about EOLC. Although ADs have been shown to
      reduce EOLC costs, most people do not have ADs. To address this issue, we propose
      that Congress instruct the Centers for Medicare and Medicaid Services to collect
      ADs from Medicare beneficiaries. Because ADs can improve care and reduce
      unnecessary spending, this solution would likely be attractive to a broad
      coalition of support from providers, insurers, and the public. 

PMID- 24293348
TI  - Aggressive tumors and difficult choices in acromegaly.
AB  - PURPOSE: The current article looks at some of the factors associated with
      pituitary adenomas displaying unusually aggressive biological and clinical
      behaviour in patients with acromegaly. METHODS: This was a retrospective,
      narrative review of previously published evidence chosen at the authors'
      discretion and presented from the perspective of a Latin American case study.
      FINDINGS AND CONCLUSIONS: Although most pituitary tumors in acromegalic patients
      are benign and non-aggressive many can behave more aggressively, compromising
      local surrounding structures. These lesions tend to respond poorly to
      somatostatin analogs, have a higher risk of recurrence after surgery and, thus, a
      worse prognosis. Patients with more aggressive tumors constitute a particular
      challenge, as they often require several therapeutic approaches and may be
      difficult to manage, especially when options are restricted due to limited
      resources.

PMID- 24293350
TI  - Quality indicators in acute stroke care: a prospective observational survey in 13
      Italian regions.
AB  - BACKGROUND AND AIMS: Quality monitoring has great relevance in stroke care. The
      Project "How to guarantee adherence to effective interventions in stroke care"
      aimed to estimate adherence to acute-phase guidelines in stroke care in Italy.
      METHODS: A prospective observational study was performed in 27 hospitals of 13
      Italian Regions. Adherence to 15 process indicators was evaluated, comparing also
      stroke units (SU) with conventional wards. An overall score of care, defined as
      the sum of achieved indicators, was calculated. A multilevel hierarchical model
      described performance at patient, hospital and regional level. RESULTS: Overall,
      484 consecutive stroke patients (mean age, 73.4 years; 52.7 % males) were
      included. Total score ranged from 2 to 15 (mean 8.5 +/- 2.4). SU patients were
      more often evaluated with the National Institutes of Health Stroke Scale (NIHSS)
      within 24 h, had more frequently an assessment of pre- and post-stroke
      disability, and a CT scan the same or the day after admission. Regional-hospital-
      and patient-level variability explained, respectively, 25, 34, and 41 % of total
      score variance. In multivariate models, patients >80 years vs. younger showed a
      change in total score of -0.45 (95 % CI -0.79 to -0.12), and those with NIHSS
      >=14 vs. <=5 of -0.92 (95 % CI -1.53 to -0.30). A negative change means a worse
      adjusted average adherence to process indicators. SU admission increased total
      score of 1.55 (95 % CI 0.52-2.58). CONCLUSIONS: Our data confirm the need of
      quality monitoring in stroke care. Although SU patients showed a better adherence
      to quality indicators, overall compliance was unsatisfactory.

PMID- 24293351
TI  - PTEN loss and KRAS activation leads to the formation of serrated adenomas and
      metastatic carcinoma in the mouse intestine.
AB  - Mutation or loss of the genes PTEN and KRAS have been implicated in human
      colorectal cancer (CRC), and have been shown to co-occur despite both playing a
      role in the PI3' kinase (PI3'K) pathway. We investigated the role of these genes
      in intestinal tumour progression in vivo, using genetically engineered mouse
      models, with the aim of generating more representative models of human CRC.
      Intestinal-specific deletion of Pten and activation of an oncogenic allele of
      Kras was induced in wild-type (WT) mice and mice with a predisposition to adenoma
      development (Apc(fl/+) ). The animals were euthanized when they became
      symptomatic of a high tumour burden. Histopathological examination of the tissues
      was carried out, and immunohistochemistry used to characterize signalling pathway
      activation. Mutation of Pten and Kras resulted in a significant life-span
      reduction of mice predisposed to adenomas. Invasive adenocarcinoma was observed
      in these animals, with evidence of activation of the PI3'K pathway but no
      metastasis. However, mutation of Pten and Kras in WT animals not predisposed to
      adenomas led to perturbed homeostasis of the intestinal epithelium and the
      development of hyperplastic polyps, dysplastic sessile serrated adenomas and
      metastasizing adenocarcinomas with serrated features. These studies demonstrate
      synergism between Pten and Kras mutations in intestinal tumour progression, in an
      autochthonous and immunocompetent murine model, with potential application to
      preclinical drug testing. In particular, they show that Pten and Kras mutations
      alone predispose mice to the spectrum of serrated lesions that reflect the
      serrated pathway of CRC progression in humans.

PMID- 24293352
TI  - Pharmacological studies confirm neurotoxic metabolite(s) produced by the bloom
      forming Cylindrospermopsis raciborskii in Hungary.
AB  - A rapid cyanobacterial bloom of Cylindrospermopsis raciborskii (3.2 * 10(4)
      filaments/mL) was detected early November, 2012, in the Fancsika pond (East
      Hungary). The strong discoloration of water was accompanied by a substantial fish
      mortality (even dead cats were seen on the site), raising the possibility of some
      toxic metabolites in the water produced by the bloom-forming cyanobacteria (C.
      raciborskii). The potential neuronal targets of the toxic substances in the bloom
      sample were studied on identified neurons (RPas) in the central nervous system of
      Helix pomatia. The effects of the crude aqueous extracts of the Fancsika bloom
      sample (FBS) and the laboratory isolate of C. raciborskii from the pond (FLI)
      were compared with reference samples: C. raciborskii ACT 9505 (isolated in 1995
      from Lake Balaton, Hungary), the cylindrospermopsin producer AQS, and the
      neurotoxin (anatoxin-a, homoanatoxin-a) producer Oscillatoria sp. (PCC 6506)
      strains. Electrophysiological tests showed that both FBS and FLI samples as well
      the ACT 9505 extracts modulate the acetylcholine receptors (AChRs) of the
      neurons, evoking ACh agonist effects, then inhibiting the ACh-evoked neuronal
      responses. Dose-response data suggested about the same range of toxicity of FBS
      and FLI samples (EC50  = 0.397 mg/mL and 0.917 mg/mL, respectively) and ACT 9505
      extracts (EC50  = 0.734 mg/mL). The extract of the neurotoxin-producing PCC 6506
      strain, however, proved to be the strongest inhibitor of the ACh responses on the
      same neurons (EC50  = 0.073 mg/mL). The presented results demonstrated an
      anatoxin-a-like cholinergic inhibitory effects of cyanobacterial extracts (both
      the environmental FBS sample, and the laboratory isolate, FLI) by some (yet
      unidentified) toxic components in the matrix of secondary metabolites. Previous
      pharmacological studies of cyanobacterial samples collected in other locations
      (Balaton, West Hungary) resulted in similar conclusions; therefore, we cannot
      exclude that this chemotype of C. raciborskii which produce anatoxin-a like
      neuroactive substances is more widely distributed in this region.

PMID- 24293353
TI  - Intranasal steroids for acute sinusitis.
AB  - BACKGROUND: Acute sinusitis is a common reason for primary care visits. It causes
      significant symptoms and often results in time off work and school. OBJECTIVES:
      We examined whether intranasal corticosteroids (INCS) are effective in relieving
      symptoms of acute sinusitis in adults and children. SEARCH METHODS: We searched
      CENTRAL 2013, Issue 4, MEDLINE (January 1966 to May week 2, 2013), EMBASE (1990
      to May 2013) and bibliographies of included studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing INCS treatment to placebo or no
      intervention in adults and children with acute sinusitis. Acute sinusitis was
      defined by clinical diagnosis and confirmed by radiological evidence or by nasal
      endoscopy. The primary outcome was the proportion of participants with either
      resolution or improvement of symptoms. Secondary outcomes were any adverse events
      that required discontinuation of treatment, drop-outs before the end of the
      study, rates of relapse, complications and return to school or work. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data,
      assessed trial quality and resolved discrepancies by consensus. MAIN RESULTS: No
      new trials were found for inclusion in this update. Four studies involving 1943
      participants with acute sinusitis met our inclusion criteria. The trials were
      well-designed and double-blind and studied INCS versus placebo or no intervention
      for 15 or 21 days. The rates of loss to follow-up were 7%, 11%, 41% and 10%. When
      we combined the results from the three trials included in the meta-analysis,
      participants receiving INCS were more likely to experience resolution or
      improvement in symptoms than those receiving placebo (73% versus 66.4%; risk
      ratio (RR) 1.11; 95% confidence interval (CI) 1.04 to 1.18). Higher doses of INCS
      had a stronger effect on improvement of symptoms or complete relief: for
      mometasone furoate 400 ug versus 200 ug (RR 1.10; 95% CI 1.02 to 1.18 versus RR
      1.04; 95% CI 0.98 to 1.11). No significant adverse events were reported and there
      was no significant difference in the drop-out and recurrence rates for the two
      treatment groups and for groups receiving higher doses of INCS. AUTHORS'
      CONCLUSIONS: Current evidence is limited for acute sinusitis confirmed by
      radiology or nasal endoscopy but supports the use of INCS as a monotherapy or as
      an adjuvant therapy to antibiotics. Clinicians should weigh the modest but
      clinically important benefits against possible minor adverse events when
      prescribing therapy.

PMID- 24293354
TI  - Common vole (Microtus arvalis) ecology and management: implications for risk
      assessment of plant protection products.
AB  - Common voles (Microtus arvalis) are common small mammals in some European
      landscapes. They can be a major rodent pest in European agriculture and they are
      also a representative generic focal small herbivorous mammal species used in risk
      assessment for plant protection products. In this paper, common vole population
      dynamics, habitat and food preferences, pest potential and use of the common vole
      as a model small wild mammal species in the risk assessment process are reviewed.
      Common voles are a component of agroecosystems in many parts of Europe,
      inhabiting agricultural areas (secondary habitats) when the carrying capacity of
      primary grassland habitats is exceeded. Colonisation of secondary habitats occurs
      during multiannual outbreaks, when population sizes can exceed 1000 individuals
      ha(-1) . In such cases, in-crop common vole population control management has
      been practised to avoid significant crop damage. The species' status as a crop
      pest, high fecundity, resilience to disturbance and intermittent colonisation of
      crop habitats are important characteristics that should be reflected in risk
      assessment. Based on the information provided in the scientific literature, it
      seems justified to modify elements of the current risk assessment scheme for
      plant protection products, including the use of realistic food intake rates,
      reduced assessment factors or the use of alternativee focal rodent species in
      particular European regions. Some of these adjustments are already being applied
      in some EU member states. Therefore, it seems reasonable consistently to apply
      such pragmatic and realistic approaches in risk assessments for plant protection
      products across the EU.

PMID- 24293355
TI  - Periodontal tissue engineering strategies based on nonoral stem cells.
AB  - Periodontal disease is an inflammatory disease which constitutes an important
      health problem in humans due to its enormous prevalence and life threatening
      implications on systemic health. Routine standard periodontal treatments include
      gingival flaps, root planning, application of growth/differentiation factors or
      filler materials and guided tissue regeneration. However, these treatments have
      come short on achieving regeneration ad integrum of the periodontium, mainly due
      to the presence of tissues from different embryonic origins and their complex
      interactions along the regenerative process. Tissue engineering (TE) aims to
      regenerate damaged tissue by providing the repair site with a suitable scaffold
      seeded with sufficient undifferentiated cells and, thus, constitutes a valuable
      alternative to current therapies for the treatment of periodontal defects. Stem
      cells from oral and dental origin are known to have potential to regenerate these
      tissues. Nevertheless, harvesting cells from these sites implies a significant
      local tissue morbidity and low cell yield, as compared to other anatomical
      sources of adult multipotent stem cells. This manuscript reviews studies
      describing the use of non-oral stem cells in tissue engineering strategies,
      highlighting the importance and potential of these alternative stem cells sources
      in the development of advanced therapies for periodontal regeneration.

PMID- 24293356
TI  - Improved meta-analytic methods show no effect of chromium supplements on fasting
      glucose.
AB  - The trace mineral chromium has been extensively researched over the years in its
      role in glucose metabolism. Dietary supplement companies have attempted to make
      claims that chromium may be able to treat or prevent diabetes. Previous meta
      analyses/systematic reviews have indicated that chromium supplementation results
      in a significant lowering of fasting glucose in diabetics but not in
      nondiabetics. A meta-analysis was conducted using an alternative measure of
      effect size, d(ppc2) in order to account for changes in the control group as well
      as the chromium group. The literature search included MEDLINE, the Cochrane
      Controlled Trials Register, and previously published article reviews, systematic
      reviews, and meta-analyses. Included studies were randomized, placebo-controlled
      trials in the English language with subjects that were nonpregnant adults, both
      with and without diabetes. Sixteen studies with 809 participants (440 diabetics
      and 369 nondiabetics) were included in the analysis. Screening for publication
      bias indicated symmetry of the data. Tests of heterogeneity indicated the use of
      a fixed-effect model (I2 = 0 %). The analysis indicated that there was no
      significant effect of chromium supplementation in diabetics or nondiabetics, with
      a weighted average effect size of 0.02 (SE = 0.07), p = 0.787, CI 95 % = -0.12 to
      0.16. Chromium supplementation appears to provide no benefits to populations
      where chromium deficiency is unlikely.

PMID- 24293357
TI  - Prostate angiogenesis in development and inflammation.
AB  - BACKGROUND: Prostatic inflammation is an important factor in development and
      progression of BPH/LUTS. This study was performed to characterize the normal
      development and vascular anatomy of the mouse prostate and then examine, for the
      first time, the effects of prostatic inflammation on the prostate vasculature.
      METHODS: Adult mice were perfused with India ink to visualize the prostatic
      vascular anatomy. Immunostaining was performed on the E16.5 UGS and the P5, P20,
      and adult prostate to characterize vascular development. Uropathogenic E. coli
      1677 was instilled transurethrally into adult male mice to induce prostate
      inflammation. RT-PCR and BrdU labeling was performed to assay anigogenic factor
      expression and endothelial proliferation, respectively. RESULTS: An artery on the
      ventral surface of the bladder trifurcates near the bladder neck to supply the
      prostate lobes and seminal vesicle. Development of the prostatic vascular system
      is associated with endothelial proliferation and robust expression of pro
      angiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, and
      Figf. Bacterial-induced prostatic inflammation induced endothelial cell
      proliferation and increased vascular density but surprisingly decreased pro
      angiogenic factor expression. CONCLUSIONS: The striking decrease in pro
      angiogenic factor mRNA expression associated with endothelial proliferation and
      increased vascular density during inflammation suggests that endothelial response
      to injury is not a recapitulation of normal development and may be initiated and
      regulated by different regulatory mechanisms.

PMID- 24293359
TI  - On-chip photonic memory elements employing phase-change materials.
AB  - Phase-change materials integrated into nanophotonic circuits provide a flexible
      way to realize tunable optical components. Relying on the enormous refractive
      index contrast between the amorphous and crystalline states, such materials are
      promising candidates for on-chip photonic memories. Nonvolatile memory operation
      employing arrays of microring resonators is demonstrated as a route toward all
      photonic chipscale information processing. 

PMID- 24293358
TI  - Guidance of transcatheter aortic valve replacement by echocardiography.
AB  - Transcatheter aortic valve replacement (TAVR) has recently emerged as an
      alternative to surgical aortic valve replacement for patients with severe aortic
      stenosis who are at "high risk" or deemed inoperable. Careful pre-procedural
      preparation requires multi-modality imaging. Intra-procedural imaging frequently
      relies on transesophageal echocardiography (TEE). This review will discuss the
      role of TEE in pre-implantation assessment, intra-procedural guidance, and post
      implantation evaluation. 

PMID- 24293361
TI  - Monte Carlo calculation of patient organ doses from computed tomography.
AB  - In this study, we aimed to evaluate quantitatively the patient organ dose from
      computed tomography (CT) using Monte Carlo calculations. A multidetector CT unit
      (Aquilion 16, TOSHIBA Medical Systems) was modeled with the GMctdospp (IMPS,
      Germany) software based on the EGSnrc Monte Carlo code. The X-ray spectrum and
      the configuration of the bowtie filter for the Monte Carlo modeling were
      determined from the chamber measurements for the half-value layer (HVL) of
      aluminum and the dose profile (off-center ratio, OCR) in air. The calculated HVL
      and OCR were compared with measured values for body irradiation with 120 kVp. The
      Monte Carlo-calculated patient dose distribution was converted to the absorbed
      dose measured by a Farmer chamber with a (60)Co calibration factor at the center
      of a CT water phantom. The patient dose was evaluated from dose-volume histograms
      for the internal organs in the pelvis. The calculated Al HVL was in agreement
      within 0.3% with the measured value of 5.2 mm. The calculated dose profile in air
      matched the measured value within 5% in a range of 15 cm from the central axis.
      The mean doses for soft tissues were 23.5, 23.8, and 27.9 mGy for the prostate,
      rectum, and bladder, respectively, under exposure conditions of 120 kVp, 200 mA,
      a beam pitch of 0.938, and beam collimation of 32 mm. For bones of the femur and
      pelvis, the mean doses were 56.1 and 63.6 mGy, respectively. The doses for bone
      increased by up to 2-3 times that of soft tissue, corresponding to the ratio of
      their mass-energy absorption coefficients.

PMID- 24293360
TI  - A novel TaMYB4 transcription factor involved in the defence response against
      Puccinia striiformis f. sp. tritici and abiotic stresses.
AB  - MYB transcription factors are a large family of proteins involved in the
      regulation of secondary metabolism and cell shape, the enhancement of disease
      resistance and the response to different stresses. In this study, the role of
      TaMYB4 in wheat against biotic and abiotic stresses was investigated. TaMYB4 was
      cloned from wheat cv. Suwan11 [the leaves were infected with Puccinia striiformis
      f.sp. tritici (Pst)]; the TaMYB4 protein is 243 amino acids in length. In
      addition, TaMYB4 exhibited high similarity with BdMYB4 from Brachypodium
      distachyon, which was also identified as a member of the R2R3-MYB family of
      genes. Furthermore, transient expression analysis showed that the deduced TaMYB4
      protein was localised in the nucleus of onion epidermal cells. Additionally, a
      yeast one-hybrid assay revealed that TaMYB4 exhibits transcriptional activity and
      the C-terminus is necessary for the activation of transcription. The transcript
      levels of TaMYB4 were observed directly and were found to be significantly
      upregulated in the early stage and 48 h after inoculation with the incompatible
      Pst. The transcripts of TaMYB4 were detected in the wheat roots, culms and
      leaves. Moreover, the transcription of TaMYB4 was induced by salicylic acid,
      ethylene, abscisic acid and methyl jasmonate hormones. The same results were
      obtained with cold and wound treatments. Furthermore, the knockdown of TaMYB4
      expression using virus-induced gene silencing enhanced the susceptibility of
      wheat cultivar Suwon11 to the incompatible race of Pst. These results demonstrate
      that TaMYB4 plays a role in the wheat response to biotic stress. 

PMID- 24293363
TI  - Aim for production of Glycyrrhizae Radix in Japan (3): development of a new
      licorice cultivar.
AB  - The development of cultivars is indispensable for the establishment of a method
      aimed at producing licorice in Japan. The cultivar should have the following
      attributes: (1) the underground parts should grow vigorously; (2) the
      glycyrrhizin (GL) content must be 2.5 % or greater; and (3) the architecture of
      the aerial parts should be erect. A new cultivar suitable for the domestic
      production of licorice was developed by crossbreeding between strain A-19 (with a
      high GL content) as the mother and strain G-6 (with vigorous growth) as the
      father. After 2 years of cultivation, strain C-2 exhibited vigorous growth; the
      fresh weight and stem diameter were 148.8 g and 0.89 mm, respectively. Moreover,
      the dry-weight GL and total flavonoid contents of the new cultivar (strain C-2)
      from cultured plants were 3.61 and 1.365 %, respectively.

PMID- 24293362
TI  - Mitogen-activated protein kinase signaling and its association with oxidative
      stress and apoptosis in lead-exposed hepatocytes.
AB  - Lead toxicity has become a serious public health concern all over the world.
      Previous studies have shown that lead induces biochemical and structural changes
      in liver. However, although lead is known to alter liver functions, the
      underlying molecular mechanisms of hepatotoxicity are not yet clear. We
      hypothesized that a correlation exists between oxidative stress, apoptosis and
      mitogen-activated protein kinases (MAPKs) in lead-exposed liver. Wistar rats were
      treated with 0, 0.5%, and 1% lead acetate for 3d, 14d, and 35d and sacrificed the
      next day. On 4d, oxidative stress and apoptosis were correlated with
      downregulated expressions of ERK1/2 and p38-MAPKalpha/beta, and upregulated
      expressions of JNK1/3 in males. In females, the correlation was with
      downregulated expressions of ERK1/2 and upregulated expressions of p38
      MAPKalpha/beta and JNK1/3. On 15d, the correlation was observed with upregulated
      expressions of p38-MAPKalpha/beta in males and downregulated expressions of p38
      MAPKalpha/beta in females. In both sexes, a correlation was observed with
      upregulated expressions of ERK1/2 and JNK1/3 in 1% groups. On 36d, the
      correlation was observed with downregulated expressions of p38-MAPKalpha/beta in
      males and their upregulated expressions in females. Time-dependent increase in
      lipid peroxidation on 15d and 36d correlated with upregulated expressions of p38
      MAPKalpha/beta in females and ERK1/2 in 1% groups in both sexes. The lower dose
      induced more apoptosis up to 15d in females and the higher dose induced in males
      on 36d. Generally, the female livers had more p38-MAPKalpha/beta than the male
      livers. On 36d, the female livers showed more p38-MAPKalpha/beta and JNK1/3 than
      the male livers. In conclusion, although not clearly defined, a correlation
      exists among oxidative stress, apoptosis, and the MAPKs in lead-exposed
      hepatocytes. The sex-dependent effects may be due to differences in hormonal or
      other physiological mechanisms. In lead-exposed hepatocytes, the apoptosis may be
      induced via oxidative stress-mediated alterations in the MAPKs.

PMID- 24293364
TI  - A novel cell adhesion region in tropoelastin mediates attachment to integrin
      alphaVbeta5.
AB  - Tropoelastin protein monomers assemble to form elastin. Cellular integrin
      alphaVbeta3 binds RKRK at the C-terminal tail of tropoelastin. We probed cell
      interactions with tropoelastin by deleting the RKRK sequence to identify other
      cell-binding interactions within tropoelastin. We found a novel human dermal
      fibroblast attachment and spreading site on tropoelastin that is located
      centrally in the molecule. Inhibition studies demonstrated that this cell
      adhesion was not mediated by either elastin-binding protein or
      glycosaminoglycans. Cell interactions were divalent cation-dependent, indicating
      integrin dependence. Function-blocking monoclonal antibodies revealed that alphaV
      integrin(s) and integrin alphaVbeta5 specifically were critical for cell adhesion
      to this part of tropoelastin. These data reveal a common alphaV integrin-binding
      theme for tropoelastin: alphaVbeta3 at the C terminus and alphaVbeta5 at the
      central region of tropoelastin. Each alphaV region contributes to fibroblast
      attachment and spreading, but they differ in their effects on cytoskeletal
      assembly. 

PMID- 24293365
TI  - Very low density lipoprotein receptor (VLDLR) expression is a determinant factor
      in adipose tissue inflammation and adipocyte-macrophage interaction.
AB  - Obesity is associated with adipose tissue remodeling, characterized by adipocyte
      hypertrophy and macrophage infiltration. Previously, we have shown that very low
      density lipoprotein receptor (VLDLR) is virtually absent in preadipocytes but is
      strongly induced during adipogenesis and actively participates in adipocyte
      hypertrophy. In this study, we investigated the role of VLDLR in adipose tissue
      inflammation and adipocyte-macrophage interactions in wild type and VLDLR
      deficient mice fed a high fat diet. The results show that VLDLR deficiency
      reduced high fat diet-induced inflammation and endoplasmic reticulum (ER) stress
      in adipose tissue in conjunction with reduced macrophage infiltration, especially
      those expressing pro-inflammatory markers. In adipocyte culture, VLDLR deficiency
      prevented adipocyte hypertrophy and strongly reduced VLDL-induced ER stress and
      inflammation. Likewise, cultures of primary peritoneal macrophages show that
      VLDLR deficiency reduced lipid accumulation and inflammation but did not alter
      chemotactic response of macrophages to adipocyte signals. Moreover, VLDLR
      deficiency tempered the synergistic inflammatory interactions between adipocytes
      and macrophages in a co-culture system. Collectively, these results show that
      VLDLR contributes to adipose tissue inflammation and mediates VLDL-induced lipid
      accumulation and induction of inflammation and ER stress in adipocytes and
      macrophages. 

PMID- 24293366
TI  - Matrilin-1 is essential for zebrafish development by facilitating collagen II
      secretion.
AB  - Matrilin-1 is the prototypical member of the matrilin protein family and is
      highly expressed in cartilage. However, gene targeting of matrilin-1 in mouse did
      not lead to pronounced phenotypes. Here we used the zebrafish as an alternative
      model to study matrilin function in vivo. Matrilin-1 displays a multiphasic
      expression during zebrafish development. In an early phase, with peak expression
      at about 15 h post-fertilization, matrilin-1 is present throughout the zebrafish
      embryo with exception of the notochord. Later, when the skeleton develops,
      matrilin-1 is expressed mainly in cartilage. Morpholino knockdown of matrilin-1
      results both in overall growth defects and in disturbances in the formation of
      the craniofacial cartilage, most prominently loss of collagen II deposition. In
      fish with mild phenotypes, certain cartilage extracellular matrix components were
      present, but the tissue did not show features characteristic for cartilage. The
      cells showed endoplasmic reticulum aberrations but no activation of XBP-1, a
      marker for endoplasmic reticulum stress. In severe phenotypes nearly all
      chondrocytes died. During the early expression phase the matrilin-1 knockdown had
      no effects on cell morphology, but increased cell death was observed. In
      addition, the broad deposition of collagen II was largely abolished.
      Interestingly, the early phenotype could be rescued by the co-injection of mRNA
      coding for the von Willebrand factor C domain of collagen IIalpha1a, indicating
      that the functional loss of this domain occurs as a consequence of matrilin-1
      deficiency. The results show that matrilin-1 is indispensible for zebrafish
      cartilage formation and plays a role in the early collagen II-dependent
      developmental events. 

PMID- 24293367
TI  - The two Na+ sites in the human serotonin transporter play distinct roles in the
      ion coupling and electrogenicity of transport.
AB  - Neurotransmitter transporters of the SLC6 family of proteins, including the human
      serotonin transporter (hSERT), utilize Na(+), Cl(-), and K(+) gradients to induce
      conformational changes necessary for substrate translocation. Dysregulation of
      ion movement through monoamine transporters has been shown to impact neuronal
      firing potentials and could play a role in pathophysiologies, such as depression
      and anxiety. Despite multiple crystal structures of prokaryotic and eukaryotic
      SLC transporters indicating the location of both (or one) conserved Na(+)-binding
      sites (termed Na1 and Na2), much remains uncertain in regard to the movements and
      contributions of these cation-binding sites in the transport process. In this
      study, we utilize the unique properties of a mutation of hSERT at a single,
      highly conserved asparagine on TM1 (Asn-101) to provide several lines of evidence
      demonstrating mechanistically distinct roles for Na1 and Na2. Mutations at Asn
      101 alter the cation dependence of the transporter, allowing Ca(2+) (but not
      other cations) to functionally replace Na(+) for driving transport and promoting
      5-hydroxytryptamine (5-HT)-dependent conformational changes. Furthermore, in two
      electrode voltage clamp studies in Xenopus oocytes, both Ca(2+) and Na(+) illicit
      5-HT-induced currents in the Asn-101 mutants and reveal that, although Ca(2+)
      promotes substrate-induced current, it does not appear to be the charge carrier
      during 5-HT transport. These findings, in addition to functional evaluation of
      Na1 and Na2 site mutants, reveal separate roles for Na1 and Na2 and provide
      insight into initiation of the translocation process as well as a mechanism
      whereby the reported SERT stoichiometry can be obtained despite the presence of
      two putative Na(+)-binding sites. 

PMID- 24293368
TI  - Crystal structure of the tetrameric fibrinogen-like recognition domain of
      fibrinogen C domain containing 1 (FIBCD1) protein.
AB  - The high resolution crystal structures of a recombinant fragment of the C
      terminal fibrinogen-like recognition domain of FIBCD1, a vertebrate receptor that
      binds chitin, have been determined. The overall tetrameric structure shows
      similarity in structure and aggregation to the horseshoe crab innate immune
      protein tachylectin 5A. The high affinity ligand N-acetylmannosamine (ManNAc)
      binds in the S1 site, predominantly via the acetyl group with the oxygen and
      acetamide nitrogen hydrogen-bonded to the protein and the methyl group inserted
      into a hydrophobic pocket. The binding of the ManNAc pyranose ring differs
      markedly between the two independent subunits, but in all structures the binding
      of the N-acetyl group is conserved. In the native structure, a crystal contact
      results in one of the independent protomers binding the first GlcNAc of the
      Asn(340) N-linked glycan on the other independent protomer. In the ligand-bound
      structure this GlcNAc is replaced by the higher affinity ligand ManNAc. In
      addition, a sulfate ion has been modeled into the electron density at a location
      similar to the S3 binding site in L-ficolin, whereas in the native structure an
      acetate ion has been placed in the S1 N-acetyl binding site, and a sulfate ion
      has been placed adjacent to this site. These ion binding sites are ideally placed
      to receive the N-acetyl and sulfate groups of sulfated GalNAc residues of
      glycosaminoglycans such as chondroitin and dermatan sulfate. Together, these
      structures give insight into important determinants of ligand selectivity,
      demonstrating versatility in recognition and binding while maintaining
      conservation in N-acetyl and calcium binding. 

PMID- 24293370
TI  - Associations between teasing, quality of life, and physical activity among
      preadolescent children.
AB  - OBJECTIVE: This study assessed longitudinal associations between preadolescent's
      physical activity engagement (PA), health-related quality of life (HRQOL), and
      teasing during physical activity (TDPA). METHODS: 108 children completed measures
      of PA, HRQOL, and TDPA during fourth or fifth grade and 1 year later. Potential
      longitudinal associations between study variables were tested using structural
      equation modeling. RESULTS: Weight status emerged as an important moderator of
      the structural relationships. TDPA predicted later HRQOL for children with
      overweight and obesity, whereas HRQOL predicted later PA in children with normal
      weight. Both groups demonstrated a significant association between TDPA and HRQOL
      cross-sectionally. CONCLUSIONS: Children with overweight or obesity who
      experience TDPA are more likely to report poorer subsequent HRQOL. Children with
      normal weight who experience TDPA are at increased risk for reduced PA 1 year
      later. Efforts to reduce TDPA may benefit children's HRQOL and increase PA
      participation.

PMID- 24293369
TI  - The A2A adenosine receptor is a dual coding gene: a novel mechanism of gene usage
      and signal transduction.
AB  - The A2A adenosine receptor (A2AR) is a G protein-coupled receptor and a major
      target of caffeine. The A2AR gene encodes alternative transcripts that are
      initiated from at least two independent promoters. The different transcripts of
      the A2AR gene contain the same coding region and 3'-untranslated region and
      different 5'-untranslated regions that are highly conserved among species. We
      report here that in addition to the production of the A2AR protein, translation
      from an upstream, out-of-frame AUG of the rat A2AR gene produces a 134-amino acid
      protein (designated uORF5). An anti-uORF5 antibody recognized a protein of the
      predicted size of uORF5 in PC12 cells and rat brains. Up-regulation of A2AR
      transcripts by hypoxia led to increased levels of both the A2AR and uORF5
      proteins. Moreover, stimulation of A2AR increased the level of the uORF5 protein
      via post-transcriptional regulation. Expression of the uORF5 protein suppressed
      the AP1-mediated transcription promoted by nerve growth factor and modulated the
      expression of several proteins that were implicated in the MAPK pathway. Taken
      together, our results show that the rat A2AR gene encodes two distinct proteins
      (A2AR and uORF5) in an A2AR-dependent manner. Our study reveals a new example of
      the complexity of the mammalian genome and provides novel insights into the
      function of A2AR. 

PMID- 24293371
TI  - Changes in body composition and use of blood cholesterol lowering drugs predict
      changes in blood lipids during 12 weeks of resistance exercise training in old
      adults.
AB  - PURPOSE: Aging is associated with an impairment of blood lipids. The present
      study investigated the response of blood lipids to resistance exercise in old
      adults. The particular aim was to investigate whether the response of blood
      lipids is associated with changes in body composition of blood lipid medication.
      METHODS: Subjects (N = 236, 73.7 +/- 5.7 years, 58.2 % female) participated in a
      12-week resistance exercise program (3 times/week; 3 sets, 6-8 repetitions at 75
      80 % of the 1-repetition maximum), designed to increase strength and muscle mass
      of major muscle groups. Body composition, drug use, triglycerides (TG), total
      cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) were assessed at baseline and endpoint. RESULTS: The concentrations of HDL
      (-6 mg/dl), LDL (-18 mg/dl), TC (-26 mg/dl) and TG (-12 mg/g) decreased
      significantly during the study period. A reduction in fat mass by 1 kg predicted
      a reduction in TG (5.0 mg/dl, P = 0.017) and a gain in lean body mass by 1 kg
      predicted also a reduction in TG (-4.5 mg/dl, P = 0.023). The use of blood
      cholesterol lowering drugs predicted greater reductions in TC (-16.9 mg/dl, P =
      0.032) and LDL (-11.8 mg/dl, P = 0.038) during training. CONCLUSIONS: TG, TC, LDL
      and HDL decreased significantly after 12 weeks of progressive resistance exercise
      in old adults. Changes in body composition, i.e., reduction in fat mass and gain
      in lean body mass improved the blood lipid profile. Use of blood lipid lowering
      drugs was associated with greater reductions in TC and LDL after the training.

PMID- 24293372
TI  - Preoperative transarterial chemoembolization and resection for hepatocellular
      carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors.
AB  - BACKGROUND: To explore long-term predictors of outcome after TACE and resection
      in a population of patients with hepatocellular carcinoma (HCC). METHODS: A total
      of 648 had received TACE before liver resection (TACE group) while 10,431
      patients had received liver resection without TACE (LR group). Propensity scores
      were calculated by entering the patient data into a logistic regression model for
      predicting HCC outcomes. RESULTS: Compared to the LR group, the TACE group did
      not significantly differ in disease-free survival (DFS) (median, 17 months in the
      TACE group vs. 13 months in the LR group; P = 0.410) and overall-survival (OS)
      (median, 56 months in the TACE group vs. 54 months in the LR group; P = 0.777).
      The TACE group also showed that gender, liver cirrhosis, CCI score, hospital
      volume, and surgeon volume were independently associated with DFS while gender,
      CCI score and hospital level were independently associated with DFS/OS.
      CONCLUSIONS: This population-based cohort study provides compelling evidence that
      preoperative TACE does not significantly reduce DFS or OS in patients with
      resectable HCC. Moreover, long-term outcomes for these procedures are
      significantly associated with patient characteristics and hospital
      characteristics. Medical professionals and health care providers should carefully
      evaluate candidates for preoperative TACE in patients with resectable HCC.

PMID- 24293373
TI  - CYP1A2 rs762551 polymorphism contributes to risk of lung cancer: a meta-analysis.
AB  - Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated
      with risk of lung cancer by influencing the function of CYP1A2. However, previous
      studies on the association between CYP1A2 rs762551 polymorphism and risk of lung
      cancer reported inconsistent findings. We performed a meta-analysis of the
      published case-control studies to assess the association between CYP1A2 rs762551
      polymorphism and risk of lung cancer. PubMed and Embase were searched to identify
      relevant studies on the association between CYP1A2 rs762551 polymorphism and risk
      of lung cancer, and seven studies with a total of 3,320 subjects were finally
      included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence
      interval (95%CI) was calculated to evaluate the association. Meta-analysis of
      total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of
      lung cancer under all four genetic models (C versus A: OR = 1.26, 95%CI 1.13 to
      1.40, P < 0.001; CC versus AA: OR = 1.61, 95%CI 1.28 to 2.04, P < 0.001; CC
      versus AA/AC: OR = 1.52, 95%CI 1.11 to 2.09, P = 0.009; CC/AC versus AA: OR =
      1.28, 95%CI 1.10 to 1.48, P = 0.001). Subgroup analysis based on ethnicity
      further suggested that CYP1A2 rs762551 polymorphism was associated with risk of
      lung cancer in Caucasians. These results from the meta-analysis suggest that
      CYP1A2 rs762551 polymorphism contributes to risk of lung cancer. 

PMID- 24293374
TI  - Effect of cyclin G2 on proliferative ability of prostate cancer PC-3 cell.
AB  - This study aimed to analyze the expression, clinical significance of cyclin G2
      (CCNG2) in prostate carcinoma, and the biological effect in its cell line by
      CCNG2 overexpression. Immunohistochemistry and Western blot were used to analyze
      CCNG2 protein expression in 85 cases of prostate cancer and normal tissues to
      study the relationship between CCNG2 expression and clinical factors. CCNG2
      lentiviral vector and empty vector were, respectively, transfected into prostate
      cancer PC-3 cell line. Reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot were used to detect the mRNA level and protein of CCNG2. MTT
      assay and cell cycle were also conducted as to the influence of the upregulated
      expression of CCNG2 that might be found on PC-3 cells biological effect. The
      level of CCNG2 protein expression was found to be significantly lower in prostate
      cancer tissue than normal tissues (P < 0.05). The level of CCNG2 protein
      expression was not correlated with age, PSA contention, and tumor size (P <
      0.05), but it was correlated with lymph node metastasis, clinic stage, and
      Gleason score (P < 0.05). The result of biological function shown that PC-3 cell
      transfected CCNG2 had a lower survival fraction, more percentage of the G0/G1
      phases, and lower CDK2 protein expression compared with PC-3 cell untransfected
      CCNG2 (P < 0.05). CCNG2 expression decreased in prostate cancer and correlated
      significantly with lymph node metastasis, clinic stage, and Gleason score,
      suggesting that CCNG2 may play important roles as a negative regulator to
      prostate cancer cell.

PMID- 24293375
TI  - N stages of the seventh edition of TNM Classification are the most intensive
      variables for predictions of the overall survival of gastric cancer patients who
      underwent limited lymphadenectomy.
AB  - The objective of this study was to explore the prognostic prediction rationality
      of the seventh edition N stage for gastric cancer (GC) patients who underwent the
      limited lymphadenectomy. Clinicopathological data of 769 GC patients who
      underwent the curative resection between 1997 and 2006 were analyzed for
      demonstration that the seventh edition N stage had the significant superiorities
      of prognostic prediction to the patients who underwent the limited
      lymphadenectomy. Although the extent of lymphadenectomy was associated with the
      overall survival (OS) of gastric cancer (GC) patients, the N stages of the
      seventh edition of the TNM Classification were identified as the most intensively
      independent predictors of GC prognosis. Using stratum analysis, the 5-year
      survival rate of patients who underwent limited lymphadenectomy was observed to
      be significantly different from that of patients who underwent extended
      lymphadenectomy, regardless of the extent of lymph node metastasis. Multinomial
      logistic regression analysis revealed that combining the extents of lymph node
      metastasis and lymphadenectomy could improve the prediction accuracy of patient
      survival status. Case control analysis showed that regardless of the extent of
      lymphadenectomy, the seventh edition N stages featured significant superiority
      for OS evaluation of GC patients. The seventh edition N stage had the prediction
      rationality for the OS of GC patients who underwent the limited lymphadenectomy. 

PMID- 24293377
TI  - POLYS 2.0: An open source software package for building three-dimensional
      structures of polysaccharides.
AB  - This article describes an update of POLYS, the POLYSaccharide builder, for
      generating three-dimensional structures of polysaccharides and complex
      carbohydrates (Engelsen et al., Biopolymers 1996, 39, 417-433). POLYS is written
      in portable ANSI C and is now released under an open source license. Using this
      software, complex branched carbohydrate structures and polysaccharides can be
      constructed from their primary structure and the relevant monosaccharides stored
      in database containing information on optimized glycosidic linkage geometries.
      The constructed three-dimensional structures are described as Cartesian
      coordinate files which can be used as input to other molecular modeling software.
      The new version of POLYS includes a large database of monosaccharides and a
      helical generator to build and optimize regular single helix or double helix
      structures. To demonstrate the efficiency of POLYS to build carbohydrate
      structures, four examples of increasing complexity are presented in the
      manuscript, from simple alpha glucans over complex starch fragments and the
      double helical structure of amylopectin to the mega-oligosaccharide
      RhamnoGalacturonan II.

PMID- 24293376
TI  - MiR-495 regulates proliferation and migration in NSCLC by targeting MTA3.
AB  - Our previous studies have showed that metastasis-associated protein 3 (MTA 3) is
      overexpressed in non-small cell lung cancer (NSCLC) tissue, and increased MTA3
      mRNA levels is a risk factor of lymph node metastasis. Using bioinformatics
      analyses, we found that MTA3 was a potential target of miR-495. However, the
      pathophysiological role of miR-495 and its relevance to the growth and
      development of NSCLC have yet to be investigated. The purpose of this study was
      to elucidate the molecular mechanisms by which miR-495 acts as a tumor suppressor
      in NSCLC. qRT-PCR data showed significant downregulation of miR-495 in 56 NSCLC
      tissue samples and 5 lung cancer cell lines, compared with their adjacent normal
      tissue; furthermore, western blotting analysis revealed MTA3 protein was
      overexpressed in the tumor samples compared with the matched adjacent normal
      tissue. MiR-495 was shown to not only inhibit the proliferation of lung cancer
      cells (A549 and Calu-3) but also to inhibit cell migration in vitro. Using
      western blotting and luciferase assays, MTA3 was identified as a target of miR
      495. These findings suggest the importance of miR-495 targeting of MTA3 in the
      regulation of lung cancer growth and migration. 

PMID- 24293378
TI  - Mesenchymal stem cells and their subpopulation, pluripotent muse cells, in basic
      research and regenerative medicine.
AB  - Mesenchymal stem cells (MSCs) have gained a great deal of attention for
      regenerative medicine because they can be obtained from easy accessible
      mesenchymal tissues, such as bone marrow, adipose tissue, and the umbilical cord,
      and have trophic and immunosuppressive effects to protect tissues. The most
      outstanding property of MSCs is their potential for differentiation into cells of
      all three germ layers. MSCs belong to the mesodermal lineage, but they are known
      to cross boundaries from mesodermal to ectodermal and endodermal lineages, and
      differentiate into a variety of cell types both in vitro and in vivo. Such
      behavior is exceptional for tissue stem cells. As observed with hematopoietic and
      neural stem cells, tissue stem cells usually generate cells that belong to the
      tissue in which they reside, and do not show triploblastic differentiation.
      However, the scientific basis for the broad multipotent differentiation of MSCs
      still remains an enigma. This review summarizes the properties of MSCs from
      representative mesenchymal tissues, including bone marrow, adipose tissue, and
      the umbilical cord, to demonstrate their similarities and differences. Finally,
      we introduce a novel type of pluripotent stem cell, multilineage-differentiating
      stress-enduring (Muse) cells, a small subpopulation of MSCs, which can explain
      the broad spectrum of differentiation ability in MSCs.

PMID- 24293379
TI  - Prevalence of eating disorders in middle-aged women.
AB  - OBJECTIVE: Little is known about the prevalence and correlates of eating
      disorders (ED) in middle-aged women. METHOD: We mailed anonymous questionnaires
      to 1,500 Austrian women aged 40-60 years, assessing ED (defined by DSM-IV),
      subthreshold ED, body image, and quality of life. We broadly defined
      "subthreshold ED" by the presence of either (1) binge eating with loss of control
      or (2) purging behavior, without requiring any of the other usual DSM-IV criteria
      for frequency or severity of these symptoms. RESULTS: Of the 715 (48%)
      responders, 33 [4.6%; 95% confidence interval (CI): 3.3-6.4%] reported symptoms
      meeting full DSM-IV criteria for an ED [bulimia nervosa = 10; binge eating
      disorder = 11; eating disorder not otherwise specified (EDNOS) = 12]. None
      displayed anorexia nervosa. Another 34 women (4.8%; CI: 3.4-6.6%) displayed
      subthreshold ED. These women showed levels of associated psychopathology
      virtually equal to the women with full-syndrome diagnoses. DISCUSSION: ED appear
      common in middle-aged women, with a preponderance of binge eating disorder and
      EDNOS diagnoses as compared to the "classical" diagnoses of anorexia and bulimia
      nervosa. Interestingly, middle-aged women with even very broadly defined
      subthreshold ED showed distress and impairment comparable to women with full
      scale ED.

PMID- 24293380
TI  - Evaluation of the accuracy of preoperative MRI in measuring myometrial
      infiltration in endometrial carcinoma.
AB  - The aim of our study was to evaluate the diagnostic performance of magnetic
      resonance imaging (MRI) in the pretreatment evaluation of myometrium invasion in
      endometrial cancer. Our retrospective study concerns 89 patients with endometrial
      cancer, who had preoperative MR evaluation of myometrium invasion and we compared
      it with histological results. Considering histological type and grade, we had
      excluded patients with poor prognosis, and separately evaluated those cases where
      the depth of myometrium invasion is the main prognostic factor determining the
      choice treatment. Of the 89 cases MRI had accurately evaluated the depth of
      myometrial invasion in 75 patients. Based on data from all cases, we found the
      sensitivity of detection of deep myometrial infiltration by MRI (Sv) 71 %,
      specificity (Sp) 92 %, accuracy (Acc) 84 %, positive predictive value (PPV) 86 %
      and negative predictive value (NPV) 83 %. Excluding patients with poor prognosis
      according to histology and grade, these data were Sv 71 %, Sp 95 %, Acc 87 %, PPV
      90 %, NPV 84 %. In conclusion, MRI is an efficient diagnostic tool in assessing
      myometrial infiltration, which is necessary for proper preoperative staging and
      therapy planning, including evaluation of the necessity of lymphadenectomy.
      Certain factors may interfere with evaluation of MRI results, thus hindering the
      precise determination of the level of myometrial infiltration.

PMID- 24293381
TI  - Clinicopathological and molecular spectrum of ewing sarcomas/PNETs, including
      validation of EWSR1 rearrangement by conventional and array FISH technique in
      certain cases.
AB  - Over the years, a wide clinicopathological spectrum has been identified within
      Ewing family of tumors (EFTs). As these tumors are chemosensitive, their correct
      and timely identification is necessary. The aims of this study were (1) to
      present the diverse clinicopathological and molecular profile of EFTs in our
      settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially
      for application of ancillary techniques, namely RT-PCR for specific transcripts
      (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and
      (3) to show the utility of tissue microarray in establishing a new FISH test.
      Fifty-eight EFTs were identified in 38 males and 20 females within an age-range
      of 1-65 years (median, 16), mostly in lower extremities (14) (24.1 %).
      Therapeutically, most patients underwent neoadjuvant chemotherapy with subsequent
      surgery. Histopathologically, diagnosis of EFTs was initially offered in 41/58
      (70.6 %) tumors. On review, 59 % tumors showed diffuse pattern, while 41 %
      displayed rosettes. Immunohistochemically, tumor cells were mostly diffusely
      positive for CD99 (48/52) (92.3 %); FLI-1 (17/18) (94.4 %); variably for BCL2
      (16/18) (88.8 %), synaptophysin (6/20) (35 %), S100-P (2/7) (28.5 %), CD56 (2/5)
      (40 %), NSE (2/5) (40 %), calponin (3/4) (75 %), EMA (5/24) (20.8 %) and CK
      (3/24) (12.5 %), the latter two mostly focally. Fifty five tumors were EWS-FLI1
      positive, while a single tumor was EWS-ERG positive. Sensitivity for PCR was 61
      %. EWSR1 rearrangement was detected by FISH in 12/13 Ewing sarcomas/PNETs.
      Sensitivity for EWSR1 test was 92.3 % and specificity was 100 %. Thirty-eight
      tumors, including 14 molecular confirmed EFTs and 21 other tumors were tested for
      EWSR1 rearrangement. Among 21 unrelated tumors, EWSR1 rearrangement was detected
      in few myoepithelial tumors, occasional desmoplastic small round cell tumor and
      an extraskeletal myxoid chondrosarcoma. Further, a tissue microarray with a
      separate set of 8 EFTs, confirmed at another laboratory was analysed for
      validation of EWSR1 rearrangement test. 23/28 (82.1 %) tissue cores of the tissue
      microarray, stained by FISH were interpretable, including EWSR1 rearrangement,
      detected in 20/28 tissue cores; not detected in 3 liver cores and uninterpretable
      in 5 (17.8 %) cores. Classical EFTs can be diagnosed with diffuse, membranous
      CD99 positivity, intranuclear FLI1 positivity and LCA negativity in malignant
      round cells. In unconventional cases, it is indispensable to reveal the
      concomitant fusion m-RNA by RT-PCR. In case of negative molecular results, it is
      necessary to prove EWSR1 rearrangement by FISH. These tests should be interpreted
      with clinicopathological correlation. Tissue microarrays for FISH are useful
      during validation of a new test, especially when sarcomas like EFTs show less
      genetic heterogeneity within tumor cells.

PMID- 24293382
TI  - Fuzzy clustering analysis of osteosarcoma related genes.
AB  - Osteosarcoma is the most common malignant bone-tumor with a peak manifestation
      during the second and third decade of life. In order to explore the influence of
      genetic factors on the mechanism of osteosarcoma by analyzing the inter
      relationship between osteosarcoma and its related genes, and then provide
      potential genetic references for the prevention, diagnosis and treatment of
      osteosarcoma, we collected osteosarcoma related gene sequences in Genebank of
      National Center for Biotechnology Information (NCBI) and local alignment analysis
      for a pair of sequences was carried out to identify the measurement association
      among related sequences. Then fuzzy clustering method was used for clustering
      analysis so as to contact the unknown genes through the consistent osteosarcoma
      related genes in one class. From the result of fuzzy clustering analysis, we
      could classify the osteosarcoma related genes into two groups and deduced that
      the genes clustered into one group had similar function. Based on this knowledge,
      we found more genes related to the pathogenesis of osteosarcoma and these genes
      could exert similar function as Runx2, a risk factor confirmed in osteosarcoma,
      this study may help better understand the genetic mechanism and provide new
      molecular markers and therapies for osteosarcoma. 

PMID- 24293383
TI  - Protective effects of diallyl disulfide on carbon tetrachloride-induced
      hepatotoxicity through activation of Nrf2.
AB  - This study was conducted to investigate the potential effects of diallyl
      disulfide (DADS) on carbon tetrachloride (CCl4 )-induced acute hepatotoxicity and
      to determine the molecular mechanisms of protection offered by DADS in rats. DADS
      was administered orally at 50 and 100 mg/kg/day once daily for 5 consecutive days
      prior to CCl4 administration. The single oral dose of CCl4 (2 mL/kg) caused a
      significant elevation in serum aspartate and alanine aminotransferase activities,
      which decreased upon pretreatment with DADS. Histopathological examinations
      showed extensive liver injury, characterized by extensive hepatocellular
      degeneration/necrosis, fatty changes, inflammatory cell infiltration, and
      congestion, which were reversed following pretreatment with DADS. The effects of
      DADS on cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl4
      bioactivation, were also investigated. DADS pretreatment resulted in a
      significant decrease in CYP2E1 protein levels in dose-dependent manner. In
      addition, CCl4 caused a decrease in protein level of cytoplasmic nuclear factor
      E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2
      concurrent with downregulation of detoxifying phase II enzymes and a decrease in
      antioxidant enzyme activities. In contrast, DADS prevented the depletion of
      cytoplasmic Nrf2 and enhanced nuclear translocation of Nrf2, which, in turn,
      upregulated antioxidant and/or phase II enzymes. These results indicate that the
      protective effects of DADS against CCl4 -induced hepatotoxicity possibly involve
      mechanisms related to its ability to induce antioxidant or detoxifying enzymes by
      activating Nrf2 and block metabolic activation of CCl4 by suppressing CYP2E1.

PMID- 24293384
TI  - The effects of L-arginine, alone and combined with vitamin C, on mineral status
      in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in
      male rats on a high-fat diet.
AB  - The aim of this study was to evaluate the influence of the intake of L-arginine
      alone and of L-arginine with vitamin C on mineral concentration in rats fed with
      a high-fat diet, and to assess the lipid glucose, insulin, and total antioxidant
      status (TAS) and tumor necrosis factor (TNF) alpha serum levels that result.
      Wistar rats were assigned to groups fed with either a standard control diet (C),
      a diet high in fat (FD), a diet high in fat with L-arginine, or a diet high in
      fat with L-arginine and vitamin C. After 6 weeks, the length and weight of the
      rats were measured, and the animals were euthanized. The liver, spleen, kidneys,
      pancreas, heart, and gonads were collected, as were blood samples. The total
      serum cholesterol, triglyceride, fasting glucose, insulin, TAS, and TNF alpha
      levels were measured. The tissue calcium, magnesium, iron, zinc, and copper
      concentrations were determined. It was found that L-arginine supplementation
      diminished the effect of the modified diet on the concentration of iron in the
      liver and spleen and of copper in heart. At the same time, it was observed that L
      arginine supplementation reduced the effect of the high-fat diet on insulin, TNF
      alpha, and TAS. The combination of L-arginine and vitamin C produced a similar
      effect on the mineral levels in the tissues as did L-arginine used alone.
      Moreover, positive correlations between serum insulin and iron in the liver,
      between TNF alpha and iron in the liver, and between TNF alpha and copper in the
      heart were observed. The level of TAS in serum was inversely correlated with the
      copper level in the heart and the iron level in the liver. We concluded that the
      beneficial influence of L-arginine on insulin, TAS, and TNF alpha serum level is
      associated with changes in the iron and copper status in rats fed with a high-fat
      diet. No synergistic effect of L-arginine and vitamin C in the biochemical
      parameters or in the mineral status in rats fed with the modified diet was
      observed.

PMID- 24293385
TI  - The effects of glial cell line-derived neurotrophic factor on the in vitro
      matured porcine oocyte transcriptome.
AB  - It is well documented that oocytes from small antral follicles are less competent
      than those derived from large follicles, and we have previously shown that glial
      cell line-derived neurotrophic factor (GDNF) enhances developmental competence in
      oocytes from antral follicles. Exactly how GDNF effects this change and if it
      depends on the stage of oocyte development is currently unknown. The objective of
      this study was to examine the transcriptomic effects of follicle size and GDNF on
      the in vitro maturation of porcine oocytes. Microarray analysis uncovered
      differentially expressed transcripts among in vitro-matured porcine oocytes from
      different-size antral follicles, in the absence or presence of GDNF. Oocytes
      isolated from small follicles showed a lower state of maturation than those from
      large follicles, with several transcripts associated with meiotic arrest.
      Addition of GDNF to the culture media had effects that depended on the stage of
      the follicle from which the oocyte was isolated, with those from small follicles
      showing decreased expression of genes associated with acetyltransferase activity
      while those from large follicles showed decreased metabolic activity. In summary,
      our results revealed considerable differences between the transcriptomes of small
      and large-follicle-derived oocytes. Furthermore, GDNF affects the developmental
      competence of oocytes in follicle-stage dependent manner. Thus, improving our
      understanding of the requirements for successful in vitro maturation of porcine
      oocytes will inform current reproductive technologies, with implications for the
      future of animal and human health.

PMID- 24293386
TI  - Incomplete contingency tables with censored cells with application to estimating
      the number of people who inject drugs in Scotland.
AB  - Estimating the size of hidden or difficult to reach populations is often of
      interest for economic, sociological or public health reasons. In order to
      estimate such populations, administrative data lists are often collated to form
      multi-list cross-counts and displayed in the form of an incomplete contingency
      table. Log-linear models are typically fitted to such data to obtain an estimate
      of the total population size by estimating the number of individuals not observed
      by any of the data-sources. This approach has been taken to estimate the current
      number of people who inject drugs (PWID) in Scotland, with the Hepatitis C virus
      diagnosis database used as one of the data-sources to identify PWID. However, the
      Hepatitis C virus diagnosis data-source does not distinguish between current and
      former PWID, which, if ignored, will lead to overestimation of the total
      population size of current PWID. We extend the standard model-fitting approach to
      allow for a data-source, which contains a mixture of target and non-target
      individuals (i.e. in this case, current and former PWID). We apply the proposed
      approach to data for PWID in Scotland in 2003, 2006 and 2009 and compare with the
      results from standard log-linear models.

PMID- 24293387
TI  - New cytotoxic apotirucallanes from the leaves of Walsura trichostemon.
AB  - Three new apotirucallanes (1-3) were isolated from the leaves of Walsura
      trichostemon. Their structures were identified by interpretation of their
      spectroscopic data as well as comparison with those reported in the literature.
      In addition, all isolated compounds were evaluated for their cytotoxicity against
      KB and HeLa cells. 

PMID- 24293389
TI  - Tissue engineering in the trachea.
AB  - This review summarizes efforts to generate an autologous tissue-engineered
      trachea (TET) using various biomaterial or cell sources to make tracheal
      cartilage to form the structural components of a functional tracheal replacement.
      Biomechanical assessments of the TET showed that the cartilage stiffness was
      excellent in the nude models; however, the sheep autologous TET did not provide
      sufficient support and collapsed easily. As a result, tissue engineering
      technology is still far from allowing the functional recovery of patients who
      suffer from severe tracheal disease. On the other hand, there are several
      clinical reports seeding cells to decellularized tissue using tissue engineering
      techniques. However, the working mechanisms of the tissue-engineered trachea
      remain unclear. Nevertheless, we believe that the field of tissue engineering has
      great potential for surmounting these obstacles and allowing us to generate
      functional tracheal replacements in the near future.

PMID- 24293388
TI  - The potential of encapsulating "raw materials" in 3D osteochondral gradient
      scaffolds.
AB  - Scaffolds with continuous gradients in material composition and bioactive signals
      enable a smooth transition of properties at the interface. Components like
      chondroitin sulfate (CS) and bioactive glass (BG) in 3D scaffolds may serve as
      "raw materials" for synthesis of new extracellular matrix (ECM), and may have the
      potential to completely or partially replace expensive growth factors. We
      hypothesized that scaffolds with gradients of ECM components would enable
      superior performance of engineered constructs. Raw material encapsulation altered
      the appearance, structure, porosity, and degradation of the scaffolds. They
      allowed the scaffolds to better retain their 3D structure during culture and
      provided a buffering effect to the cells in culture. Following seeding of rat
      mesenchymal stem cells, there were several instances where glycosaminoglycan
      (GAG), collagen, or calcium contents were higher with the scaffolds containing
      raw materials (CS or BG) than with those containing transforming growth factor
      (TGF)-beta3 or bone morphogenetic protein (BMP)-2. It was also noteworthy that a
      combination of both CS and TGF-beta3 increased the secretion of collagen type II.
      Moreover, cells seeded in scaffolds containing opposing gradients of CS/TGF-beta3
      and BG/BMP-2 produced clear regional variations in the secretion of tissue
      specific ECM. The study demonstrated raw materials have the potential to create a
      favorable microenvironment for cells; they can significantly enhance the
      synthesis of certain extracellular matrix (ECM) components when compared to
      expensive growth factors; either alone or in combination with growth factors they
      can enhance the secretion of tissue specific matrix proteins. Raw materials are
      promising candidates that can be used to either replace or be used in combination
      with growth factors. Success with raw materials in lieu of growth factors could
      have profound implications in terms of lower cost and faster regulatory approval
      for more rapid translation of regenerative medicine products to the clinic.

PMID- 24293390
TI  - An updated meta-analysis of the association between ADIPOQ rs2241766 polymorphism
      and colorectal cancer.
AB  - Adiponectin (ADIPOQ) is a cytokine produced by adipose tissue involved in
      carcinogenesis. ADIPOQ SNP rs2241766 has been extensively studied in colorectal
      cancer (CRC) community with contentious and conflicting conclusions. The
      objective of this study was to comprehensively assess the association between SNP
      rs2241766 and CRC risk. PubMed, Embase, CNKI, as well as the references of the
      retrieved articles were searched to identify the eligible studies for this meta
      analysis. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to
      assess the association. We also examined the heterogeneity and publication bias
      and performed sensitivity analyses. Seven studies with 2,414 cases and 2,796
      controls together did not show any significant association between SNP rs2241766
      and CRC risk. Subgroup analyses by ethnicity and sample size also failed to
      provide statistically significant evidence. This meta-analysis demonstrates that
      ADIPOQ SNP rs2241766 may not represent as an effect modifier for the risk of CRC.

PMID- 24293391
TI  - HIF-1alpha P582S and A588T polymorphisms and digestive system cancer risk-a meta
      analysis.
AB  - Hypoxia-inducible factor-1 (HIF-1) influences cancer progression and metastasis
      through various mechanisms, and HIF-1alpha polymorphisms are reportedly
      associated with many cancers; however, the associations of HIF-1alpha P582S and
      A588T polymorphisms with the risk of digestive system cancer remain inconclusive.
      To understand the role of HIF-1alpha P582S and A588T genotypes in digestive
      cancer development, we conducted a comprehensive meta-analysis involving 1,517
      cases and 3,740 controls. Overall, the P582S polymorphism was not significantly
      associated with digestive system cancers in all genotypes. By contrast, the A588T
      polymorphism was significantly associated with digestive system cancers in the
      dominant model (TT/AT vs. AA: OR = 3.17, 95% CI: 1.21, 8.25; P heterogeneity <
      0.001). In subgroup analysis for cancer types, the two polymorphisms were only
      associated with increased risk of pancreatic cancer (P582S: SS vs. PP: OR = 2.51,
      95% CI: 1.31, 4.81; SS vs. PP/PS: OR = 8.73, 95% CI: 1.33, 57.1; A588T: TT vs.
      AA: OR = 9.30, 95% CI: 1.12, 77.6; P heterogeneity = 0.478; TT vs. AA/AT: OR =
      3.14, 95% CI: 1.99, 4.97; P heterogeneity = 0.098; TT/AT vs. AA: OR = 8.65, 95%
      CI: 1.05, 71.6; P heterogeneity = 0.418). According to the source of ethnicity,
      the P582S and the A588T polymorphisms are both significantly associated with an
      increased risk of cancer among Caucasians in the homozygote model (SS vs. PP: OR
      = 2.41, 95% CI: 1.24, 4.691; P heterogeneity = 0.010; TT vs. AA: OR = 98.6, 95%
      CI: 4.37, 2,224; P heterogeneity = 0.040) and the recessive model (SS vs. PP/PS:
      OR = 9.48, 95% CI: 1.12, 80.3; P heterogeneity < 0.001; TT vs. AA/AT: OR = 82.7,
      95% CI: 3.79, 1,802; P heterogeneity = 0.041). Our findings suggest that the HIF
      1alpha A588T polymorphism is significantly associated with higher cancer risk and
      the P582S polymorphism is significantly associated with pancreatic cancer risk.
      Furthermore, the effect of both polymorphisms on digestive system cancer is more
      pronounced among Caucasians than that among Asians.

PMID- 24293392
TI  - MDM2 rs2279744 polymorphism and endometrial cancer: a meta-analysis.
AB  - Case-control studies on the association between mouse double minute 2 homolog
      (MDM2) rs2279744 polymorphism and endometrial cancer have provided either
      controversial or inconclusive results. To clarify the effect of MDM2 rs2279744
      polymorphism on the risk of endometrial cancer, a meta-analysis of all case
      control observational studies was performed. Pooled odds ratios (ORs) for various
      polymorphisms were estimated using random and fixed effect models. Q-statistic
      was used to evaluate the homogeneity, and Egger and Begg tests were used to
      assess publication bias. Overall, the MDM2 rs2279744 polymorphism was associated
      with a risk of endometrial cancer (OR = 0.76; 95% CI = 0.64-0.90 for allele
      contrast, p = 0.002, P(het) = 0.003). The contrast of homozygotes and the
      recessive and dominant models produced the same pattern of results as the allele
      contrast. In the analysis stratified by ethnicity, significant associations were
      found in the Caucasian population in all of the genetic models. Our pooled data
      suggest evidence for a major role of MDM2 rs2279744 polymorphism in the
      carcinogenesis of endometrial cancer, especially among Caucasian populations.

PMID- 24293393
TI  - The growth inhibitory effect of 17-DMAG on ALK and MYCN double-positive
      neuroblastoma cell line.
AB  - Neuroblastoma (NB), an embryonal tumor derived from the neural crest, originates
      from sympathetic nerve system, manifests as thoracic, paraspinous or abdominal
      tumors, and metastases to bone in high-risk cases. Although NB stands as the most
      common solid tumor in early childhood and accounts for about 15% of total
      pediatric cancer death, there has been limited success in searching for novel
      therapeutic regimen for this lethal disease during the past two decades. Numerous
      epidemiological and clinical studies have pinpointed anaplastic lymphoma kinase
      (ALK) and MYCN as potent governors for NB malignant behavior. ALK and MYCN
      amplification and constitutive active mutations are common in high-risk NB
      patients. However, there is still lack of evidence showing that a small molecule
      compound could simultaneously inhibits ALK and MYCN and plays strong negative
      regulatory roles in NB. Here, we showed that 17-DMAG, a well-known HSP-90
      inhibitor, significantly inhibits NB cell growth, arrests cell cycle, and
      strongly induces NB cell apoptosis. Interestingly, our data suggests that NB
      cells with both ALK and MYCN amplification/mutation are more sensitive to 17-DMAG
      treatment, while NB cells with only ALK or MYCN amplification are less sensitive
      and NB cells without ALK or MYCN amplification/mutation are least sensitive.
      Moreover, we also found that knocking down ALK and MYCN additively inhibits NB
      cell growth and that transduction of MYCN largely abolished the ALK-dependent NB
      cell growth, indicating that there is a cross-talk between MYCN and ALK signaling
      machinery. Our results provide proof-of-principle that 17-DMAG strongly inhibits
      NB cell growth by targeting both ALK and MYCN. Our findings might shed a light
      for further investigation of novel small molecule compound which is safe and
      exerts similar strong effects in vivo as novel approaches for management of high
      risk NB.

PMID- 24293394
TI  - Genome-wide pathway analysis in neuroblastoma.
AB  - The aim of this study was to identify candidate single-nucleotide polymorphisms
      (SNPs) that might play a role in susceptibility to neuroblastoma, elucidate their
      potential mechanisms, and generate SNP-to-gene-to-pathway hypotheses. A genome
      wide association study (GWAS) dataset of neuroblastoma that included 442,976 SNPs
      from 1,627 neuroblastoma patients and 3,254 control subjects of European descent
      was used in this study. The identify candidate causal SNPs and pathways
      (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis
      identified 15 candidate SNPs, 10 genes, and 31 pathways, which revealed 10
      hypothetical biological mechanisms. The strongest hypothetical biological
      mechanism was one wherein SNPrs40401 modulates the role of IL3 in several
      pathways and conditions, including the stem pathway, asthma (hsa05310), the
      dendritic cell pathway, and development (0.001 < p < 0.004; 0.001 < FDR < 0.033).
      The second strongest mechanism identified was that in which rs1048108 and
      rs16852600 alter the function of BARD1, which negatively regulates developmental
      process and modulates processes including cell development and programmed cell
      death (0.001 < p < 0.004; 0.001 < FDR < 0.033). The third mechanism identified
      was one wherein rs1939212 modulated CFL1, resulting in negative regulation of
      development, cell death, neural crest cell migration, and apoptosis (0.001 < p <
      0.004; 0.001 < FDR < 0.033). By using the ICSNPathway to analyze neuroblastoma
      GWAS data, 15 candidate SNPs, 10 genes including IL3, BARD1, and CFL, and 31
      pathways were identified that might contribute to the susceptibility of patients
      to neuroblastoma.

PMID- 24293396
TI  - Ochratoxin A biocontrol and biodegradation by Bacillus subtilis CW 14.
AB  - BACKGROUND: Ochratoxin A (OTA) is a mycotoxin produced by some Aspergillus and
      Penicillium species. In this study a strain of Bacillus subtilis was tested for
      its effects on OTA-producing Aspergillus and OTA degradation. The mechanisms of
      the effects were also investigated. RESULTS: A strain of Bacillus spp. isolated
      from fresh elk droppings was screened out using the methods described by Guan et
      al. (Int J Mol Sci 9:1489-1503 (2008)). The 16S rRNA gene sequence suggested that
      it was B. subtilis CW 14. It could inhibit the growth of the OTA-producing
      species Aspergillus ochraceus 3.4412 and Aspergillus carbonarius, with inhibition
      rates of 33.0 and 33.3% respectively. At 6 ug mL(-1) OTA, both viable and
      autoclaved (121  degrees C, 20 min) cells of CW 14 bound more than 60% of OTA. In
      addition, OTA was degraded by the cell-free supernatant of CW 14. By high
      performance liquid chromatography, the cell-free supernatant degraded 97.6% of
      OTA after 24 h of incubation at 30  degrees C, and no degradation products were
      produced. The fastest degradation occurred during the first 2 h. In 3 g samples
      of contaminated maize, 47.1% of OTA was degraded by 50 mL inocula of overnight
      cultures of CW 14. CONCLUSION: These findings indicated that B. subtilis CW 14
      could both prevent OTA contamination and degrade OTA in crops.

PMID- 24293397
TI  - Protective effects of placental growth factor on retinal neuronal cell damage.
AB  - Placental growth factor (PlGF) is a member of the vascular endothelial growth
      factor family. Although it has been reported that PlGF protects against neuronal
      damage in the brain, little is known about the effects of PlGF in the retina.
      Therefore, we investigated the effects of PlGF on retinal neuronal cells. To
      evaluate the effects of PlGF against L-buthionine-(S,R)-sulfoximine
      (BSO)/glutamate cell death, oxygen-glucose deprivation (OGD)-induced cell death,
      and light-induced cell death, RGC-5 and 661W cells were used. We evaluated the
      mechanism responsible for the protective effects of PlGF against retinal neuronal
      cell death by performing the examinations with U1026, which is a mitogen
      activated protein kinase (MEK) inhibitor, and LY294002, which is a
      phosphoinositide 3-kinase (PI3K) inhibitor. In addition, we measured caspase-3/7
      activity in RGC-5 cells and 661W cells. PlGF protected against RGC-5 cell death
      induced by BSO/glutamate and OGD and against 661W cell death induced by light
      irradiation. Moreover, an anti-PlGF antibody negated these protective effects.
      The protective effects of PlGF against OGD-induced RGC-5 cell death and light
      induced 661W cell death were suppressed by using an anti-PlGF antibody, U1026,
      and LY294002. Treatment with PlGF suppressed caspase-3/7 activity in both cell
      lines. We demonstrated for the first time that PlGF exerts a protective effect by
      inhibiting the activation of caspase-3/7 through the MEK and PI3K pathway in
      retinal neuronal cells. These data suggest that PlGF may be an important
      protective factor in the retina.

PMID- 24293398
TI  - The fermented non-digestible fraction of common bean (Phaseolus vulgaris L.)
      triggers cell cycle arrest and apoptosis in human colon adenocarcinoma cells.
AB  - Cancer is a leading cause of death worldwide with colorectal cancer (CRC) ranking
      as the third contributing to overall cancer mortality. Non-digestible compounds
      such as dietary fiber have been inversely associated with CRC in epidemiological
      in vivo and in vitro studies. In order to investigate the effect of fermentation
      products from a whole non-digestible fraction of common bean versus the short
      chain fatty acid (SCFAs) on colon cancer cells, we evaluated the human gut
      microbiota fermented non-digestible fraction (hgm-FNDF) of cooked common bean
      (Phaseolus vulgaris L.) cultivar Negro 8025 and a synthetic mixture SCFAs,
      mimicking their concentration in the lethal concentration 50 (SCFA-LC50) of FNDF
      (hgm-FNDF-LC50), on the molecular changes in human colon adenocarcinoma cells (HT
      29). Total mRNA from hgm-FNDF-LC50 and SCFA-LC50 treated HT-29 cells were used to
      perform qPCR arrays to determine the effect of the treatments on the
      transcriptional expression of 84 genes related to the p53-pathway. This study
      showed that both treatments inhibited cell proliferation in accordance with
      modulating RB1, CDC2, CDC25A, NFKB and E2F genes. Furthermore, we found an
      association between the induction of apoptosis and the modulation of APAF1, BID,
      CASP9, FASLG, TNFR10B and BCL2A genes. The results suggest a mechanism of action
      by which the fermentation of non-digestible compounds of common bean exert a
      beneficial effect better than the SCFA mixture by modulating the expression of
      antiproliferative and pro-apoptotic genes in HT-29 cells to a greater extent,
      supporting previous results on cell behavior, probably due to the participation
      of other compounds, such as phenolic fatty acids derivatives and biopetides. 

PMID- 24293395
TI  - Unmet needs in respiratory diseases : "You can't know where you are going until
      you know where you have been"--Anonymous.
AB  - The care of patients with respiratory diseases has improved vastly in the past 50
      years. In spite of that, there are still massive challenges that have not been
      resolved. Although the incidence of tuberculosis has decreased in the developed
      world, it is still a significant public health problem in the rest of the world.
      There are still over 2 million deaths annually from tuberculosis, with most of
      these occurring in the developing world. Even with the development of new
      pharmaceuticals to treat tuberculosis, there is no indication that the disease
      will be eradicated. Respiratory syncytial virus, severe acute respiratory
      syndrome, and pertussis are other respiratory infectious diseases with special
      problems of their own, from vaccine development to vaccine coverage. Asthma, one
      of the most common chronic diseases in children, still accounts for significant
      mortality and morbidity, as well as high health care costs worldwide. Even in
      developed countries such as the USA, there are over 4,000 deaths per year. Severe
      asthma presents a special problem, but the question is whether there can be one
      treatment pathway for all patients with severe asthma. Severe asthma is a
      heterogeneous disease with many phenotypes and endotypes. The gene for cystic
      fibrosis was discovered over 24 years ago. The promise of gene therapy as a cure
      for the disease has fizzled out, and while new antimicrobials and other
      pharmaceuticals promise improved longevity and better quality of life, the
      average life span of a patient with cystic fibrosis is still at about 35 years.
      What are the prospects for gene therapy in the twenty-first century? Autoimmune
      diseases of the lung pose a different set of challenges, including the
      development of biomarkers to diagnose and monitor the disease and biological
      modulators to treat the disease. 

PMID- 24293400
TI  - Retinal stem cells and regeneration of vision system.
AB  - The vertebrate retina is a well-characterized model for studying neurogenesis.
      Retinal neurons and glia are generated in a conserved order from a pool of
      mutlipotent progenitor cells. During retinal development, retinal stem/progenitor
      cells (RPC) change their competency over time under the influence of intrinsic
      (such as transcriptional factors) and extrinsic factors (such as growth factors).
      In this review, we summarize the roles of these factors, together with the
      understanding of the signaling pathways that regulate eye development. The
      information about the interactions between intrinsic and extrinsic factors for
      retinal cell fate specification is useful to regenerate specific retinal neurons
      from RPCs. Recent studies have identified RPCs in the retina, which may have
      important implications in health and disease. Despite the recent advances in stem
      cell biology, our understanding of many aspects of RPCs in the eye remains
      limited. PRCs are present in the developing eye of all vertebrates and remain
      active in lower vertebrates throughout life. In mammals, however, PRCs are
      quiescent and exhibit very little activity and thus have low capacity for retinal
      regeneration. A number of different cellular sources of RPCs have been identified
      in the vertebrate retina. These include PRCs at the retinal margin, pigmented
      cells in the ciliary body, iris, and retinal pigment epithelium, and Muller cells
      within the retina. Because PRCs can be isolated and expanded from immature and
      mature eyes, it is possible now to study these cells in culture and after
      transplantation in the degenerated retinal tissue. We also examine current
      knowledge of intrinsic RPCs, and human embryonic stems and induced pluripotent
      stem cells as potential sources for cell transplant therapy to regenerate the
      diseased retina.

PMID- 24293399
TI  - Risks of nutrigenomics and nutrigenetics? What the scientists say.
AB  - Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for
      beneficial applications in public health and individuals. Yet, the potential
      achievability of such promise is not without socioethical considerations that
      challenge NGx implementation. This paper focuses on the opinions of NGx
      researchers about potential risks raised by NGx. The results of an online survey
      show that these researchers (n = 126) are fairly confident about the potential
      benefits of NGx, and that most downplay its potential risks. Researchers in this
      field do not believe that NGx will reconfigure foods as medication or transform
      the conception of eating into a health hazard. The majority think that NGx will
      produce no added burden on individuals to get tested or to remain compliant with
      NGx recommendations, nor that NGx will threaten individual autonomy in daily food
      choice. The majority of researchers do not think that NGx will lead to
      discrimination against and/or stigmatization of people who do not comply with NGx
      dietary recommendations. Despite this optimism among NGx researchers, we suggest
      that key risk factors raised by the socioethical context in which NGx
      applications will be implemented need to be considered. 

PMID- 24293401
TI  - Synthesis, characterization, and antioxidant and bleomycin-dependent DNA damage
      evaluation of curcumin analogs.
AB  - In an attempt to find a new class of antioxidant agents, a series of pyrazole,
      pyridopyrazoltriazine, pyrazolotriazine, isoxazole, and pyridine-containing
      products were prepared, starting with curcumin and appropriate chemical reagents.
      Thus, curcumin 1 undergoes coupling reaction with diazonium salts 2-5 to afford
      the corresponding 4-arylazo derivatives 6-9. Heating of 6 and/or 7 in acetic acid
      furnished the corresponding pyrazolotriazines 10 and 11. Also, pyrazole and
      isoxazole derivatives were obtained upon treatment of 10 with hydrazines or
      hydroxylamine hydrochloride. Furthermore, multicomponent reaction of 10 with
      malononitrile/CH3 COONH4 or phenacylpyridinium iodide/CH3 COONH4 produced the
      corresponding bispyridines 16 and 17, respectively. Furthermore, condensation of
      10 with guanidine nitrate or thiourea gave the corresponding pyrimidines 18 and
      19, respectively. Finally, other curcumin derivatives were obtained on
      condensation of 1 with isatins and pyrazole-4-aldehyde. The newly synthesized
      compounds were evaluated as antioxidant agents. The results showed clearly that
      most of the compounds exhibited good activities, except for compounds 9 and 12.
      Compounds 1, 3, 15, and 23 exhibited high protection against DNA damage induced
      by the bleomycine-iron complex. 

PMID- 24293402
TI  - Baclofen-induced edema in alcohol use disorders.

PMID- 24293403
TI  - Synthesis of some heterofunctionalized penicillanic acid derivatives and
      investigation of their biological activities.
AB  - 6-Substituted amino-penicillanic acid esters were synthesized starting with 6
      apa. The compounds containing a 1,3-thiazole- or 1,3-thiazolidinone nucleus
      linked to the penicillanic acid skeleton via a hydrazino linkage were obtained
      from 6-apa. The treatment of carbonylamino and carbonothioylamino compounds with
      4-chlorophenacyl bromide or ethyl bromoacetate gave 6-bis{4-[1,3
      thiazol(idinone)amino]benzoyl}amino derivatives of 6-apa. Benzyl derivatives were
      synthesized in several steps, starting with 4-aminobenzoyl chloride. The
      treatment of 4-{[3-benzyl-4-oxo-1,3-thia(oxa)zolidin-2-ylidene]amino}benzoyl
      chlorides with 6-apa in ethanolic solution produced the 6-[bis(4-{[3-benzyl-4-oxo
      1,3-thiazolidin-2-ylidene]amino}benzoyl)amino] derivative of penicillanic acid,
      while the reaction of the same intermediates in DMF gave the mono-substituted
      amino derivative of 6-apa. The synthesized compounds were screened for their
      biological activities, and some of them were found to possess good to moderate
      antimicrobial activity. Moreover, some of the compounds displayed antiurease,
      anti-beta-lactamase, and/or antilipase activities. 

PMID- 24293404
TI  - Kidney regeneration and stem cells.
AB  - The kidney has the capacity to recover from ischemic and toxic insults. Although
      there has been debate about the origin of cells that replace injured epithelial
      cells, it is now widely recognized that intrinsic surviving tubular cells are
      responsible for the repair. On the other hand, the cells, which have stem cell
      like characteristics, have been isolated in the kidney using various methods, but
      it remains unknown if these stem cells actually exist in the adult kidney and if
      they are involved in kidney regeneration. This review will focus on the
      pathophysiology of kidney regeneration and the contribution of renal stem cells.
      We also discuss possible therapeutic applications to kidney disease.

PMID- 24293405
TI  - Potentially simple score of late gadolinium enhancement cardiac MR in acute
      myocarditis outcome.
AB  - PURPOSE: To determine the value of cardiac MRI for the monitoring and the
      prognosis of patients with acute myocarditis. Cardiac MRI plays an increasingly
      important role in the diagnosis of acute myocarditis. However, it is less
      established as a prognostic tool, which requires specific postprocessing of
      images. MATERIALS AND METHODS: In a prospective pilot study, we assessed the
      prognostic value of the evolution in a simplified visual quantitative score (SQS)
      of late gadolinium enhancement (LGE) between initial hospitalization and 3 months
      later. The prognostic value was assessed at 1 year using a combination of death,
      heart transplant, and confirmed recurrence as main outcome. RESULTS: Twenty-eight
      patients were included in this study. A significant correlation was found between
      LGE measured by SQS and planimetry (r = 0.95, P < 0.001). Intraobserver and
      interobserver reproducibilities were good for SQS (ICC = 0.95 [95% CI: 0.86 to
      0.98], and 0.94 [95% CI: 0.84 to 0.98], respectively). At initial
      hospitalization, patient characteristics between the two groups were similar.
      Patients with stable or increased SQS suffered more frequently from clinical
      outcome events than patients with a decrease in SQS (P = 0.02). CONCLUSION:
      Monitoring of the evolution of LGE using a simple visual score is of interest to
      identify patients at risk of pejorative prognosis after acute myocarditis.

PMID- 24293406
TI  - Crucial roles for olfactory ensheathing cells and olfactory mucosal cells in the
      repair of damaged neural tracts.
AB  - Olfactory ensheathing cells, the glial cells of the olfactory nervous system,
      exhibit unique growth-promoting and migratory properties that make them
      interesting candidates for cell therapies targeting neuronal injuries such as
      spinal cord injury. Transplantation of olfactory cells is feasible and safe in
      humans; however, functional outcomes are highly variable with some studies
      showing dramatic improvements and some no improvements at all. We propose that
      the reason for this is that the identity and purity of the cells is different in
      each individual study. We have shown that olfactory ensheathing cells are not a
      uniform cell population and that individual subpopulations of OECs are present in
      different regions of the olfactory nervous system, with strikingly different
      behaviors. Furthermore, the presence of fibroblasts and other cell types in the
      transplant can dramatically alter the behavior of the transplanted glial cells.
      Thus, a thorough characterization of the differences between olfactory
      ensheathing cell subpopulations and how the behavior of these cells is affected
      by the presence of other cell types is highly warranted.

PMID- 24293408
TI  - Reduced expression of the chromatin remodeling gene ARID1A enhances gastric
      cancer cell migration and invasion via downregulation of E-cadherin
      transcription.
AB  - The chromatin remodeling gene AT-rich interactive domain-containing protein 1A
      (ARID1A) encodes the protein BAF250a, a subunit of human SWI/SNF-related
      complexes. Recent studies have identified ARID1A as a tumor suppressor. Here, we
      show that ARID1A expression is reduced in gastric cancer (GC) tissues, which are
      significantly associated with local lymph node metastasis, tumor infiltration and
      poor patient prognosis. ARID1A silencing enforces the migration and invasion of
      GC cells, whereas ectopic expression of ARID1A inhibits migration. The adhesive
      protein E-cadherin is remarkably downregulated in response to ARID1A silencing,
      but it is upregulated by ARID1A overexpression. E-cadherin overexpression
      significantly inhibits GC cell migration and invasion, whereas CDH1 (coded E
      cadherin) silencing promotes migration. Restored expression of CDH1 in ARID1A
      silenced cell lines restores the inhibition of cell migration. Luciferase
      reporter assays and chromatin immunoprecipitation indicate that the ARID1A
      associated SWI/SNF complex binds to the CDH1 promoter and modulates CDH1
      transcription. ARID1A knockdown induces evident morphological changes of GC cells
      with increased expression of mesenchymal markers, indicating an epithelial
      mesenchymal transition. ARID1A silencing does not alter the level of beta-catenin
      but induces a subcellular redistribution of beta-catenin from the plasma membrane
      to the cytoplasm and nucleus. Immunohistochemical studies demonstrate that
      reduced expression of E-cadherin is associated with local lymph node metastasis,
      tumor infiltration and poor clinical prognosis. ARID1A and E-cadherin expression
      show a strong correlation in 75.4% of the analyzed GC tissues. They are
      synergistically downregulated in 23.5% of analyzed GC tissues. In conclusion,
      ARID1A targets E-cadherin during the modulation of GC cell migration and
      invasion. 

PMID- 24293407
TI  - WNT5A-mediated beta-catenin-independent signalling is a novel regulator of cancer
      cell metabolism.
AB  - WNT5A has been identified as an important ligand in the malignant progression of
      a number of tumours. Although WNT5A signalling is often altered in cancer, the
      ligand's role as either a tumour suppressor or oncogene varies between tumour
      types and is a contemporary issue for investigators of beta-catenin-independent
      WNT signalling in oncology. Here, we report that one of the initial effects of
      active WNT5A signalling in malignant melanoma cells is an alteration in cellular
      energy metabolism and specifically an increase in aerobic glycolysis. This was
      found to be at least in part due to an increase in active Akt signalling and
      lactate dehydrogenase (LDH) activity. The clinical relevance of these findings
      was strengthened by a strong correlation (P < 0.001) between the expression of
      WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found
      effects of WNT5A on energy metabolism in breast cancer cells, but rather than
      promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased
      oxidative phosphorylation rates in breast cancer cells. These findings support a
      new role for WNT5A in the metabolic reprogramming of cancer cells that is a
      context- dependent event. 

PMID- 24293409
TI  - Combined inhibition of Notch and JAK/STAT is superior to monotherapies and
      impairs pancreatic cancer progression.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high rate
      of metastasis. Recent studies have indicated that Notch and janus kinase 2
      (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling
      pathways are both important for the initiation and progression of PDAC. The
      purpose of this study was to determine the outcome of targeting these two tumor
      signaling pathways simultaneously both in vitro and in vivo. We assessed the
      combinational effects of the gamma-secretase inhibitor IX (GSI IX) and JAK2
      inhibitor (AG-490) on growth and epithelial plasticity of human pancreatic cancer
      cell lines, and in a genetically engineered mouse model (Pdx1-Cre, LSL-KrasG12D,
      p53(lox/+)) of PDAC. Dual treatment with GSI IX and AG-490 significantly impaired
      cell proliferation, migration, invasion, soft agar growth and apoptosis when
      compared with monotherapies. Most importantly, combinational treatment
      significantly attenuates tumor progression in vivo and suppresses conversion from
      acinar-ductal-metaplasia to PDAC. Our results suggest that targeting Notch and
      JAK2/STAT3 signaling pathways simultaneously is superior to single inhibitions,
      supporting combined treatment by GSI IX and AG-490 as a potential therapeutic
      approach for PDAC. However, the study design limits the direct transfer into the
      clinic and the impact of dual treatment in patients with PDAC remains still to be
      determined. 

PMID- 24293410
TI  - CXCL5 contributes to tumor metastasis and recurrence of intrahepatic
      cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils.
AB  - CXCL5 is a member of the CXC-type chemokine family that may play a role in
      carcinogenesis and cancer progression. This study investigates the biological
      function and clinical significance of CXCL5 in intrahepatic cholangiocarcinoma
      (ICC). We demonstrated that CXCL5 was overexpressed in ICC cell lines and tumor
      samples compared with paired normal tissues. CXCL5 had a direct chemoattractant
      effect on neutrophils in vitro through PI3K-Akt and extracellular signal
      regulated kinase 1/2 signaling pathways. In animal studies, CXCL5 promoted tumor
      growth and metastasis without altering in vitro proliferative and invasive
      ability of ICC cells, and this effect was mediated by the recruitment of
      intratumoral infiltrative neutrophils by tumor-derived CXCL5. Immunohistochemical
      analysis of ICC samples showed that overexpression of CXCL5 correlated strongly
      with intratumoral neutrophil infiltration, shorter overall survival and high
      tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone,
      or combined with the presence of intratumoral neutrophils, was an independent
      prognostic indicator for ICC. In conclusion, our data showed that CXCL5 promotes
      ICC growth and metastasis by recruiting intratumoral neutrophils. CXCL5 alone or
      combined with intratumoral neutrophils is a novel prognostic predictor for ICC
      patients and a potential therapeutic target.

PMID- 24293412
TI  - The European lung corner.

PMID- 24293411
TI  - Cancerous inhibitor of PP2A is targeted by natural compound celastrol for
      degradation in non-small-cell lung cancer.
AB  - Celastrol binds CIP2A and enhances CIP2A-CHIP interaction, leading to
      ubiquitination/degradation of CIP2A and inhibition of lung cancer cells in vitro
      and in vivo. Celastrol potentiates cisplatin's efficacy by suppressing the CIP2A
      Akt pathway, and therefore CIP2A inhibitors may represent novel therapeutics for
      cancer. 

PMID- 24293413
TI  - Putting noninvasive lung mechanics into context.

PMID- 24293414
TI  - The CFTR and EGFR relationship in airway vascular growth, and its importance in
      cystic fibrosis.

PMID- 24293415
TI  - Bronchodilator combinations for COPD: real hopes or a new Pandora's box?

PMID- 24293416
TI  - Clinical trials in idiopathic pulmonary fibrosis: a framework for moving forward.

PMID- 24293417
TI  - Therapeutic drug management: is it the future of multidrug-resistant tuberculosis
      treatment?

PMID- 24293418
TI  - Legionnaires' disease in Europe: all quiet on the eastern front?

PMID- 24293419
TI  - Avoiding overdiagnosis in lung cancer screening: the volume doubling time
      strategy.

PMID- 24293420
TI  - Does drug-induced emphysema exist?

PMID- 24293421
TI  - Canaries in the coal mine.

PMID- 24293422
TI  - Drug concentration in lung tissue in multidrug-resistant tuberculosis.

PMID- 24293424
TI  - Each December, the United Nations (UN) holds an 'International Day of Disabled
      Persons' to promote better understanding of disability. Introduction.

PMID- 24293425
TI  - Letter to the editor: "Pulsatile pulmonary artery pressure: are fluid-filled
      catheters accurate in pulmonary hypertension?".

PMID- 24293426
TI  - Reply to "Letter to the editor: 'Pulsatile pulmonary artery pressure: are fluid
      filled catheters accurate in pulmonary hypertension?'".

PMID- 24293428
TI  - CVOs quizzed on pet travel and exotic and endemic diseases.

PMID- 24293430
TI  - Assessing the impact of Typhoon Haiyan on animals in the Philippines.

PMID- 24293431
TI  - FVE backs 'suitability lists' for exotic pet species.

PMID- 24293436
TI  - Mongolian teachers look at new approaches to veterinary education.

PMID- 24293438
TI  - Industry's dismay at Defra's plans for electronic identification of sheep.

PMID- 24293439
TI  - The changing face of mastitis control.
AB  - Over the past 125 years, mastitis has been one of the most studied conditions of
      dairy cows. This is confirmed by a search of peer-reviewed literature covering
      this period, which revealed more than 12,000 papers. Yet mastitis is still one of
      the most relevant and problematic diseases to treat and control in practice,
      which is testament to the complexity and mutability of the condition. Although
      progress has been made, recent research suggests that substantial areas require
      better understanding. Here, Martin Green and Andrew Bradley reflect on the
      control of mastitis over past decades and look forward to an interesting future.

PMID- 24293440
TI  - Detecting mycobacteria in cattle blood.

PMID- 24293441
TI  - Mitral valve disease study.

PMID- 24293442
TI  - Change in advice on selecting sires and dams for breeding under the BVA/KC elbow
      dysplasia scheme.

PMID- 24293443
TI  - Reporting rabies risk.

PMID- 24293445
TI  - Grammatical exactitude.

PMID- 24293446
TI  - Pre-exposure vaccination against rabies.

PMID- 24293447
TI  - Biomechanics and load resistance of small-diameter and mini dental implants: a
      review of literature.
AB  - In recent years, the application of small-diameter and mini dental implants to
      support removable and fixed prosthesis has dramatically increased. However, the
      success of these implants under functional biting forces and the reaction of the
      bone around them need to be analyzed. This review was aimed to present studies
      that deal with the fatigue life of small-diameter and mini dental implants under
      normal biting force, and their survival rate. The numerical and experimental
      studies concluded that an increase in the risk of bone damage or implant failure
      may be assumed in critical clinical situations and implants with <3 mm diameter
      have a risk of fracture in clinical practice. The survival rate of the small
      diameter and mini dental implants over 5 years was 98.3-99.4%.

PMID- 24293451
TI  - Editorial.

PMID- 24293449
TI  - Performance of urinary NGAL and L-FABP in predicting acute kidney injury and
      subsequent renal recovery: a cohort study based on major surgeries.
AB  - BACKGROUND: Acute kidney injury (AKI) is a frequent complication of major
      surgery. The current study evaluated the power of two biomarkers [urinary
      neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid
      binding protein (L-FABP)] to detect the occurrence of AKI and to predict the
      recovery from renal dysfunction in a major surgery cohort. METHODS: In this
      prospective study, 199 patients undergoing major surgery were enrolled. Urinary
      samples collected from participants before surgery, and 0, 4, and 12 h and 1, 2,
      7, and 14 days after surgery were tested for NGAL and L-FABP. RESULTS: Thirty
      seven (18.6%) subjects developed AKI. Urinary NGAL and L-FABP were significantly
      increased from the time surgery was completed (p<0.05). The peak levels of NGAL
      and L-FABP occurred 12 and 4 h postoperatively (16.4- and 172.0-fold compared to
      baseline) in AKI group, respectively. The area under the receiver operating
      characteristic (ROC) curve (AUC) in NGAL (at 12 h), L-FABP (at 4 h), the most
      predictive model (NGAL at 12 h+L-FABP at 4 h), and the best combination at the
      same time point (12 h) was 0.83 [95% confidence interval (CI), 0.74-0.91], 0.85
      (95% CI 0.77-0.93), 0.94 (95% CI 0.89-0.98), and 0.91 (95% CI 0.85-0.97),
      respectively. However, the largest AUC of single and combined biomarkers for
      predicting non-recovery after AKI only reached 0.70. CONCLUSIONS: Urinary NGAL
      and L-FABP can be used to detect AKI and combining NGAL and L-FABP may improve
      the diagnostic performance; however, NGAL and L-FABP may be poor predictors for
      renal recovery after AKI.

PMID- 24293450
TI  - Instability of cerebrospinal fluid after delayed storage and repeated freezing: a
      holistic study by drop coating deposition Raman spectroscopy.
AB  - BACKGROUND: The handling of cerebrospinal fluid (CSF) affects the biomarker
      quantification used to diagnose Alzheimer's disease (AD). Only specialized
      centers can test for AD markers. The precise timing and freezing is required to
      correctly measure these biomarkers. Therefore, the effects of CSF storage
      temperature and repeated freeze/thaw cycles on CSF stability were investigated.
      METHODS: Drop coating deposition Raman spectroscopy in combination with principal
      component analysis was used to analyze CSF and its dialyzed form (ELISA confirmed
      the removal of up to 80% of the AD markers). The advantage of this approach is
      that no prior knowledge of the biomarkers is necessary and that both the
      concentration and the protein structure of intact CSF are analyzed. RESULTS:
      Dialyzed CSF was stable for up to 5 h after its collection, while native CSF
      started to denature nearly immediately. Most of the unstable proteins were
      denatured within 24 h. The dialyzed CSF was not affected by freeze/thaw cycles,
      but the native CSF exhibited significant progressive changes, even after the
      first freezing. The mechanism as well as the resulting structures of the freeze
      denatured proteins differed from those of the temporally denatured proteins,
      although both protein sets began with the same initial proteins. CONCLUSIONS: CSF
      must be processed immediately, within 5 h of collection. Flash cooling is
      recommended for freezing CSF, but any freeze/thaw cycle will affect the protein
      component of CSF.

PMID- 24293448
TI  - The peripheral whole-blood transcriptome of acute pyelonephritis in human
      pregnancya.
AB  - OBJECTIVE: Human pregnancy is characterized by activation of the innate immune
      response and suppression of adaptive immunity. The former is thought to provide
      protection against infection for the mother, and the latter, tolerance against
      paternal antigens expressed in fetal cells. Acute pyelonephritis is associated
      with an increased risk of acute respiratory distress syndrome and sepsis in
      pregnant (vs. nonpregnant) women. The objective of this study was to describe the
      gene expression profile (transcriptome) of maternal whole blood in acute
      pyelonephritis. METHOD: A case-control study was conducted to include pregnant
      women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34).
      Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used
      for gene expression profiling. A linear model was used to test the association
      between the presence of pyelonephritis and gene expression levels while
      controlling for white blood cell count and gestational age. A fold change of 1.5
      was considered significant at a false discovery rate of 0.1. A subset of
      differentially expressed genes (n=56) was tested with real-time quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls,
      n=59). Gene ontology and pathway analyses were applied. RESULTS: A total of 983
      genes were differentially expressed in acute pyelonephritis: 457 were upregulated
      and 526 were downregulated. Significant enrichment of 300 biological processes
      and 63 molecular functions was found in pyelonephritis. Significantly impacted
      pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction,
      (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and
      coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation
      of differential expression. CONCLUSION: This is the first study of the
      transcriptomic signature of whole blood in pregnant women with acute
      pyelonephritis. Acute infection during pregnancy is associated with the increased
      expression of genes involved in innate immunity and the decreased expression of
      genes involved in lymphocyte function.

PMID- 24293452
TI  - Association between respiratory prescribing, air pollution and deprivation, in
      primary health care.
AB  - BACKGROUND: We investigated the association between respiratory prescribing, air
      quality and deprivation in primary health care. Most previous studies have used
      data from secondary and tertiary care to quantify air pollution effects on
      exacerbations of asthma and chronic obstructive pulmonary disease (COPD).
      However, these outcomes capture patients who suffer from relatively severe
      symptoms. METHODS: This is a population-based ecological study. We analysed
      respiratory medication (salbutamol) prescribed monthly by 63 primary care
      practices, UK. Firstly, we captured the area-wide seasonal variation in
      prescribing. Then, using the area-wide variation in prescribing as an offset, we
      built a mixed-effects model to assess the remaining variation in relation to air
      quality and demographic variables. RESULTS: An increase of 10 MUg/m(3) in ambient
      PM10 was associated with an increase of 1% (95% CI: 0.1-2%) in salbutamol
      prescribing. An increase of 1 SD in income and employment deprivation was
      associated with an increase of 20.5% (95% CI: 8.8-33.4%) and 14.7% (95% CI: 4.3
      26.2%) in salbutamol prescribing rate, respectively. CONCLUSIONS: The study
      provides evidence that monthly respiratory prescribing in primary care is a
      useful indicator of the extent to which air pollution exacerbates asthma and COPD
      symptoms. Respiratory prescribing was higher on deprived populations.

PMID- 24293453
TI  - Cochrane update: building capacity in evidence-informed decision-making to
      improve public health.

PMID- 24293454
TI  - NICE public health guidance update.

PMID- 24293455
TI  - Five-year results from a phase 2 study of oral fingolimod in relapsing multiple
      sclerosis.
AB  - We present here results at 60 months (M), from the extension component of a phase
      2, randomized, placebo-controlled, double-blind, six-month study evaluating oral
      fingolimod (1.25 mg or 5 mg daily) in relapsing multiple sclerosis. Placebo
      patients from the core study were re-randomized to fingolimod 1.25 mg or 5 mg in
      the extension. All patients received 1.25 mg fingolimod after the M24 visit. A
      total of 140/281 (49.8%) patients completed M60. Fingolimod treatment was
      associated with a low annualized relapse rate (0.2 relapses/ year), low MRI
      activity, and a modest rate of disability progression in those treated for five
      years. No new safety issues were reported.

PMID- 24293456
TI  - Risk evaluation and monitoring in multiple sclerosis therapeutics.
AB  - BACKGROUND: Risk for multiple sclerosis (MS) disease-modifying therapies (DMT)
      must be assessed on an ongoing basis. Early concerns regarding the first-approved
      DMTs for MS have been mitigated, but recently licensed therapies have been linked
      to possibly greater risks. OBJECTIVES: The objective of this review is to discuss
      risk assessment in MS therapeutics based on an international workshop and
      comprehensive literature search and recommend strategies for risk
      assessment/monitoring. RESULTS: Assessment and perception of therapeutic risks
      vary between patients, doctors and regulators. Acceptability of risk depends on
      the magnitude of risk and the demonstrated clinical benefits of any agent. Safety
      signals must be distinguishable from chance occurrences in a clinical trial and
      in long-term use of medications. Post-marketing research is crucial for assessing
      longer-term safety in large patient cohorts. Reporting of adverse events is
      becoming more proactive, allowing more rapid identification of risks.
      Communication about therapeutic risks and their relationship to clinical benefit
      must involve patients in shared decision making. CONCLUSIONS: It is difficult to
      produce a general risk-assessment algorithm for all MS therapies. Specific
      algorithms are required for each DMT in every treated-patient population. New and
      evolving risks must be evaluated and communicated rapidly to allow patients and
      physicians to be well informed and able to share treatment decisions.

PMID- 24293458
TI  - Inhibition of BET bromodomain proteins as a therapeutic approach in prostate
      cancer.
AB  - BET (bromodomain and extra-terminal) proteins regulate gene expression through
      their ability to bind to acetylated chromatin and subsequently activate RNA PolII
      driven transcriptional elongation. Small molecule BET inhibitors prevent binding
      of BET proteins to acetylated histones and inhibit transcriptional activation of
      BET target genes. BET inhibitors attenuate cell growth and survival in several
      hematologic cancer models, partially through the down-regulation of the critical
      oncogene, MYC. We hypothesized that BET inhibitors will regulate MYC expression
      in solid tumors that frequently over-express MYC. Here we describe the effects of
      the highly specific BET inhibitor, I-BET762, on MYC expression in prostate cancer
      models. I-BET762 potently reduced MYC expression in prostate cancer cell lines
      and a patient-derived tumor model with subsequent inhibition of cell growth and
      reduction of tumor burden in vivo. Our data suggests that I-BET762 effects are
      partially driven by MYC down-regulation and underlines the critical importance of
      additional mechanisms of I-BET762 induced phenotypes. 

PMID- 24293459
TI  - A paradigm shift in pulmonary arterial hypertension management.

PMID- 24293460
TI  - Lymphoproliferative lung disorders: clinicopathological aspects.

PMID- 24293461
TI  - Respiratory manifestations in patients with inherited metabolic diseases.
AB  - Growing evidence indicates that inherited metabolic diseases are increasingly
      being recognised. Life expectancy for many patients is progressively improving
      because new therapeutic strategies are available. Because most inherited
      metabolic diseases are systemic disorders, virtually all organs may be involved.
      Respiratory disease complicates the management of several inherited metabolic
      diseases, either at presentation or as late-onset features. This review will
      describe the most exemplary respiratory manifestations of inherited metabolic
      diseases in childhood and adulthood. Since airways disease worsens the morbidity
      of many inherited metabolic disorders, leading to increased hospitalisations,
      mortality and overall healthcare costs, respiratory manifestations of inherited
      metabolic diseases need to be carefully recognised and treated. All patients with
      inherited metabolic disease and suspected airway disease should undergo a
      detailed diagnostic work-up. Current treatments for several inherited metabolic
      diseases (including enzyme replacement therapy, substrate reduction, bone marrow
      transplantation, or even more innovative strategies such as pharmacological
      chaperone or gene therapies) may provide significant benefits for associated
      respiratory disease. The integration of several specialists dedicated to airway
      disease management in a multidisciplinary team is essential to provide the most
      appropriate care to children and adults with inherited metabolic disease. 

PMID- 24293462
TI  - Comorbidities of COPD.
AB  - By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of
      mortality. Extrapulmonary comorbidities influence the prognosis of patients with
      COPD. Tobacco smoking is a common risk factor for many comorbidities, including
      coronary heart disease, heart failure and lung cancer. Comorbidities such as
      pulmonary artery disease and malnutrition are directly caused by COPD, whereas
      others, such as systemic venous thromboembolism, anxiety, depression,
      osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and
      anaemia, have no evident physiopathological relationship with COPD. The common
      ground between most of these extrapulmonary manifestations is chronic systemic
      inflammation. All of these diseases potentiate the morbidity of COPD, leading to
      increased hospitalisations and healthcare costs. They can frequently cause death,
      independently of respiratory failure. Comorbidities make the management of COPD
      difficult and need to be evaluated and treated adequately. 

PMID- 24293463
TI  - Systematic review of the dry powder inhalers colistimethate sodium and tobramycin
      in cystic fibrosis.
AB  - This systematic review evaluated evidence for two dry powder formulations,
      colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas
      aeruginosa in cystic fibrosis, as part of the UK national recommendation process
      for new technologies. Electronic bibliographic databases were searched in May
      2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL,
      Web of Science, Conference Proceedings Citation Index and BIOSIS Previews).
      Relevant outcomes included rate and extent of microbial response (e.g. sputum
      density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s
      (FEV1)), frequency, severity of acute exacerbations and adverse events. Three
      trials were included, and both dry powder formulations were reported to be non
      inferior in the short term to nebulised tobramycin for FEV1. However, long-term
      follow-up data were missing and the effect on exacerbation rates was not always
      reported. Whilst short-term results showed that both dry powder drugs were non
      inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3
      trials compared nebulised and dry powder colistimethate sodium. The use of FEV1
      as the primary end-point may not accurately represent changes in lung health.
      This review illustrates the difficulty in assessing new technologies where the
      evidence base is poor. 

PMID- 24293464
TI  - The need to move from 6-minute walk distance to outcome trials in pulmonary
      arterial hypertension.
AB  - Assessment of change in exercise capacity using the 6-min walk distance (6MWD)
      test has been the primary end-point in the majority of pulmonary arterial
      hypertension (PAH) clinical trials. The 6MWD has some advantages as an end-point
      in such studies. It is simple and inexpensive to perform, reproducible and
      validated. In short-term studies with small patient numbers, as is typical in a
      rare disease like PAH, using change from baseline in 6MWD as the primary outcome
      measure demonstrated statistically significant differences between placebo and
      study drugs, leading to their approval. However, there have been increasing calls
      for clinical trials to employ primary end-points that reflect long-term disease
      progression and morbidity. While the 6MWD was initially considered to be a
      potentially reliable surrogate for disease progression in PAH, there is
      increasing evidence that this is not necessarily the case. Given this, there is a
      need to re-examine the role of 6MWD in PAH trials, and to evaluate the evidence
      supporting whether there is a need to move from 6MWD to more robust measures of
      clinical outcomes, such as morbidity and mortality. However, in the clinic the
      6MWD test, alongside symptoms, haemodynamics and biomarkers, remains a useful
      tool in the assessment and management of PAH patients. 

PMID- 24293465
TI  - New perspectives in long-term outcomes in clinical trials of pulmonary arterial
      hypertension.
AB  - The past two decades have seen significant improvements in the management of
      patients with pulmonary arterial hypertension (PAH). Although outcome has
      improved, long-term prognosis remains unsatisfactory. The development of new
      treatment options is clearly important. Equally important is testing new agents
      in trials designed to provide robust evidence for sustained clinical benefits
      enabling clinicians to determine the optimal treatment strategy for individual
      patients. End-points such as the change in 6-min walk distance (6MWD) have been
      pivotal in the registration trials of currently available PAH-specific therapies.
      However, as current clinical trials enrol patients with milder disease, many
      already on background therapy, there is growing evidence that change from
      baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short
      term trials allowed for the rapid approval of PAH therapies in the past, there is
      increasing recognition that clinical trials for new agents must provide evidence
      of long-term benefits. Clinical trials need to evolve to provide the long-term,
      clinically relevant data required to appropriately assess new therapies. Event
      driven long-term morbidity and mortality trials are currently underway, and will
      provide robust data on the frequency and timing of events, and are likely to
      reflect the future of clinical trial design in PAH. 

PMID- 24293466
TI  - New horizons in pulmonary arterial hypertension therapies.
AB  - Pulmonary arterial hypertension (PAH) is a fatal disease associated with
      vasoconstriction and vascular remodelling. There are three well-known pathways
      that contribute to the pathogenesis of PAH: endothelin, nitric oxide and
      prostacyclin. Treatments targeting these pathways are well established in
      clinical practice, such as endothelin receptor antagonists, phosphodiesterase
      type-5 inhibitors and epoprostenol. New treatments have been developed with the
      aim of improving efficacy and ease of administration of therapies targeting these
      three established pathways, and several of these new treatments have recently
      undergone phase III investigation. Ongoing pre-clinical studies are also
      beginning to uncover other mechanisms that play a role in the complex
      pathobiology of PAH. These include genetic targets, transcription factors and
      signalling pathways. The discovery of new treatment targets may change the
      landscape of PAH therapy in the future. Herein, we present some of the promising
      future treatments and interesting new therapeutic targets. 

PMID- 24293467
TI  - Screening patients with scleroderma for pulmonary arterial hypertension and
      implications for other at-risk populations.
AB  - Pulmonary arterial hypertension (PAH) is a progressive vasculopathy that is
      advanced by the time symptoms develop. As symptoms are nonspecific and the
      condition uncommon, continued progression toward end-stage disease occurs for an
      average of 2 years between symptom onset and diagnosis. There is need for earlier
      diagnosis and treatment, as most patients are severely symptomatic when diagnosed
      and their mortality is high despite therapy. Screening can help; however, it is
      not straightforward due to the diversity of patient profiles and lack of
      sufficiently accurate tools. Echocardiography, currently the best available
      screening tool, lacks both sensitivity and specificity. The low prevalence of PAH
      renders many screening tools unfit for purpose. However, this may be overcome, in
      some instances, by using enrichment tools to preselect screening populations. The
      majority of data are available for systemic sclerosis. A recent study has
      demonstrated how lung function can be used to enrich PAH prevalence in a systemic
      sclerosis population. A screening bundle then selects patients for right heart
      catheterisation with improved rates of sensitivity compared to current
      guidelines. 

PMID- 24293468
TI  - Cardiac magnetic resonance imaging in pulmonary arterial hypertension.
AB  - Cardiac magnetic resonance imaging (CMRI) provides accurate information about
      right ventricular (RV) mass, RV volumes and other markers of RV function. CMRI is
      proving to be a particularly useful tool in pulmonary arterial hypertension
      (PAH), as measures of RV function have been shown to be prognostic of long-term
      outcomes in this disease. Changes in RV function can also provide important
      information about a patient's disease course and response to treatment. As CMRI
      is noninvasive it can be used to regularly monitor patients with PAH, which is an
      important advantage over invasive right heart catheterisation. This review will
      explore the use of CMRI in the context of existing monitoring tools for PAH and
      will explore the forthcoming developments that are likely to be important in the
      future monitoring of patients with PAH. 

PMID- 24293469
TI  - Understanding the impact of pulmonary arterial hypertension on patients' and
      carers' lives.
AB  - Pulmonary arterial hypertension (PAH) is a rare, debilitating and rapidly
      progressive disease. Although there have been important medical advances in PAH
      management, the search for a cure continues. Despite an increased understanding
      of the disease, data on the wider effect of PAH on patients and carers, beyond
      the clinical symptoms, are still limited. In order to explore this, a large-scale
      international survey investigated four key areas affected by PAH (physical and
      practical, emotional, social, and information needs) and provides new insight
      into patients' and carers' experiences of living with the disease. The results
      from the survey highlight not only the limited ability of patients to carry out
      everyday tasks, but also the financial impact and social isolation experienced by
      both patients and carers. The study confirmed that a decline in a patient's World
      Health Organization functional class, which indicates an increase in clinical
      severity of the disease, is associated with greater limitations. Results from the
      survey demonstrate the need for multidisciplinary PAH management and a
      comprehensive standard of care to assess and improve all aspects of well-being
      for both patients and carers. In addition, they underline the need for updated
      PAH guidelines that address these needs. 

PMID- 24293470
TI  - Pathogenesis of pulmonary arterial hypertension: lessons from cancer.
AB  - Although the causal pathomechanisms contributing to remodelling of the pulmonary
      vascular bed in pulmonary arterial hypertension (PAH) are still unclear, several
      analogous features with carcinogenesis have led to the emergence of the cancer
      like concept. The major similarities concern the altered crosstalk between cells
      from different tissue types, unexplained proliferation and survival of pulmonary
      smooth muscle and endothelial cells, the metabolic (glycolytic) shifts, and the
      association with the immune system. However, major differences between PAH and
      cancer exist, including the absence of invasion and metastasis, as well as the
      pathogenic genes involved and the degrees of angiogenesis impairment and genetic
      instability. It is clear that PAH is not a cancer, but this cancer-like concept
      has opened a new field of investigation and raises the possibility that
      antiproliferative and/or oncological drugs may exert therapeutic effects not only
      in cancer, but also in PAH. Such analogies and differences are discussed here. 

PMID- 24293471
TI  - Fibrocytes in pulmonary fibrosis: a brief synopsis.
AB  - Fibrocytes are bone marrow-derived, circulating mesenchymal progenitor cells that
      play a role in several fibrotic disorders, including lung fibrosis. They are
      attracted to injured tissue by various chemokines. It is likely that fibrocytes
      play a detrimental role in tissue homeostasis and promote fibrosis, although this
      paradigm needs further confirmation. This would make fibrocytes a possible novel
      treatment target for fibrotic disorders. Fibrocytes also have some potential as a
      biomarker for idiopathic pulmonary fibrosis (IPF) and other diseases, but the
      promising preliminary data from single centre studies still require independent
      validation. Despite several, as yet, unresolved issues, it has become clear that
      fibrocytes are more than an incidental finding in lung injury and repair, and may
      hold great promise for the future of IPF management. 

PMID- 24293472
TI  - Eisenmenger syndrome in an adult patient with a large patent ductus arteriosus.
AB  - This is the case of a young female who was seen at our adult congenital heart
      disease and pulmonary hypertension service (Royal Brompton Hospital, London, UK)
      at the age of 17 years. She initially presented at the age of 4 years with
      increasing shortness of breath. At that time, there was differential cyanosis
      with clubbing and lower oxygen saturations in the toes (82%) compared with her
      fingers (95%). On echocardiography there was evidence of severe pulmonary
      hypertension and a large patent ductus arteriosus (PDA) with low velocity
      bidirectional shunting. She underwent cardiac catheterisation at the time which
      showed a pulmonary arterial pressure equal to that of the aorta. 

PMID- 24293473
TI  - Predictive biomarkers in patients with resected non-small cell lung cancer
      treated with perioperative chemotherapy.
AB  - The aim of this article is to summarise the published data on prognostic and
      predictive biomarkers for early-stage non-small cell lung cancer (NSCLC), and
      discuss how to integrate them into clinical trials. Large phase III trials have
      been published in resected NSCLC with biomarkers identifying subsets of patients
      benefitting from perioperative chemotherapy. Initial findings of predictive
      implications for the DNA repair protein, ERCC1, were not confirmed in a larger
      series of patients due to the versatility of the commercially available
      monoclonal ERCC1 antibody. Prediction of survival by RRM1 tumour expression was
      not confirmed in a prospective phase III trial in 275 patients with stage IV
      disease, precluding its use in early-stage NSCLC. BRCA1 mRNA tumour content also
      failed to predict platinum resistance in 287 stage IV NSCLC patients included in
      a phase II trial, and the results of a similar trial in early-stage patients are
      still pending. Of the several cDNA gene expression studies in early-stage NSCLC
      with non-overlapping prognostic signatures, few have been replicated in
      independent cohorts for prognostic value, and none received external validation
      for predictive value. Therefore, use of biomarkers predicting chemotherapy
      efficacy still needs additional validation before becoming routine practice in
      oncogene-driven pan-negative NSCLC patients. 

PMID- 24293474
TI  - How to adapt the pulmonary rehabilitation programme to patients with chronic
      respiratory disease other than COPD.
AB  - Dyspnoea, fatigue, reduced exercise tolerance, peripheral muscle dysfunction and
      mood disorders are common features of many chronic respiratory disorders.
      Pulmonary rehabilitation successfully treats these manifestations in chronic
      obstructive pulmonary disease (COPD) and emerging evidence suggests that these
      benefits could be extended to other chronic respiratory conditions, although
      adaptations to the standard programme format may be required. Whilst the benefits
      of exercise training are well established in asthma, pulmonary rehabilitation can
      also provide evidence-based interventions including breathing techniques and self
      management training. In interstitial lung disease, a small number of trials show
      improved exercise capacity, symptoms and quality of life following pulmonary
      rehabilitation, which is a positive development for patients who may have few
      treatment options. In pulmonary arterial hypertension, exercise training is safe
      and effective if patients are stable on medical therapy and close supervision is
      provided. Pulmonary rehabilitation for bronchiectasis, including exercise
      training and airway clearance techniques, improves exercise capacity and quality
      of life. In nonsmall cell lung cancer, a comprehensive interdisciplinary approach
      is required to ensure the success of pulmonary rehabilitation following surgery.
      Pulmonary rehabilitation programmes provide important and underutilised
      opportunities to improve the integrated care of people with chronic respiratory
      disorders other than COPD. 

PMID- 24293475
TI  - Rituximab-induced pneumonitis mimicking miliary tuberculosis.

PMID- 24293477
TI  - MicroRNAs as regulators of tumor-associated stromal cells.

PMID- 24293478
TI  - [Prevention and cancer care in Italy at the time of the world economic crisis].

PMID- 24293479
TI  - [A free and wide debate on the future of the Italian National Health Service].

PMID- 24293480
TI  - [Why public service is to be safeguarded].

PMID- 24293481
TI  - [A debate on changes in the Italian National Health Service at the times of the
      crisis].

PMID- 24293482
TI  - [Electronic health archives are evolving].

PMID- 24293483
TI  - [In the crisis, beyond the crisis].

PMID- 24293484
TI  - [Particulate and lung cancer: there are no thresholds].

PMID- 24293485
TI  - [EpiAir Project: introduction and reading guide to the articles].

PMID- 24293486
TI  - [Environmental indicators in EpiAir2 project: air quality data for
      epidemiological surveillance].
AB  - OBJECTIVE: construction of environmental indicators of air pollution suitable for
      epidemiological surveillance in 25 Italian cities for EpiAir2 project (2006-2010)
      and presentation of the results from a 10 years of surveillance system (2001
      2010) in 10 Italian cities. DESIGN: data on particulate matter (PM10 and its fine
      fraction PM2.5), nitrogen dioxide (NO2), and ozone (O3), measured in the 2006
      2010 calendar period, were collected. Meteorological data needed to estimate
      unbiased measures of the effect of pollutants are: temperature, relative humidity
      (estimated "apparent temperature"), and barometric pressure. In continuity with
      the previous EpiAir project, the same criteria for the selection of monitoring
      stations were applied and standard methods to estimate daily environmental
      indicators were used. Furthermore, it was checked the adequacy of the selected
      data to represent the population exposure. SETTING AND PARTICIPANTS: EpiAir2
      project, relative to the period 2006-2010, involves the cities of Milano, Mestre
      Venezia, Torino, Bologna, Firenze, Pisa, Roma, Taranto, Cagliari, and Palermo,
      already included in the previous study. The city of Treviso, Trieste, Padova,
      Rovigo, Piacenza, Parma, Ferrara, Reggio Emilia, Modena, Genova, Rimini, Ancona,
      Bari, Brindisi, and Napoli are added to the previous group. RESULTS: particulate
      matter concentrations have decreased in most cities during the study period,
      while concentrations of NO2 and ozone do not show a similar clear trend. The
      analysis of the trend showed annual mean values of PM10 higher than 40 ug/m(3) in
      some areas of the Po Valley, and annual mean values of NO2 higher than 40 ug/m(3)
      in the cities of Trieste, Milano, Padova, Torino, Modena, Bologna, Roma, and
      Napoli. CONCLUSION: the enlargement of the EpiAir project to 13 other cities has
      highlighted critical issues related to the different geographical areas under
      study. Results of EpiAir2 project point out the need of a monitoring system of
      air pollution concentrations in both urban and industrial sites, in order to
      obtain reliable estimates of exposure for resident populations and to evaluate
      the related time trend.

PMID- 24293487
TI  - [Air pollution and mortality in twenty-five Italian cities: results of the
      EpiAir2 Project].
AB  - OBJECTIVES: this study aims at presenting the results from the Italian EpiaAir2
      Project on the short-term effects of air pollution on adult population (35+ years
      old) in 25 Italian cities. DESIGN: the short-term effects of air pollution on
      resident people died in their city were analysed adopting the time series
      approach. The association between increases in 10ug/m(3) in PM10, PM2.5, NO2 and
      O3 air concentration and natural, cardiac, cerebrovascular and respiratory
      mortality was studied. City-specific Poisson models were fitted to estimate the
      association of daily concentrations of pollutants with daily counts of deaths.
      The analysis took into account temporal and meteorological factors to control for
      potential confounding effect. Pooled estimates have been derived from random
      effects meta-analysis, evaluating the presence of heterogeneity in the city
      specific results. SETTING AND PARTICIPANTS: it was analysed 422,723 deaths in the
      25 cities of the project among people aged 35 years or more, resident in each
      city during the period 2006-2010. MAIN OUTCOME MEASURES: daily counts of natural,
      cardiac, cerebrovascular, and respiratory mortality, obtained from the registries
      of each city. Demographic information were obtained by record linkage procedure
      with the civil registry of each city. RESULTS: mean number of deaths for natural
      causes ranged from 513 in Rovigo to 20,959 in Rome. About 25% of deaths are due
      to cardiac diseases, 10% to cerebrovascular diseases, and 7% to respiratory
      diseases. It was found an immediate effect of PM10 on natural mortality (0.51%;
      95%CI 0.16-0.86; lag 0-1). More relevant and prolonged effects (lag 0-5) have
      been found for PM2.5 (0.78%; 95%CI 0.12-1.46) and NO2 (1.10%; 95%CI 0.63-1.58).
      Increases in cardiac mortality are associated with PM10 (0.93%; 95%CI 0.16-1.70)
      and PM2.5 (1.25%; 95%CI 0.17-2.34), while for respiratory mortality exposure to
      NO2 has an important role (1.67%; 95%CI 0.23-3.13; lag 2-5), as well as PM10
      (1.41%; 95%CI - 0.23;+3.08). Results are strongly homogeneous among cities,
      except for respiratory mortality. No effect has been found for cerebrovascular
      mortality and weak evidence of association has been observed between ozone and
      mortality. CONCLUSIONS: a clear increase in mortality associated to air
      pollutants was observed. More important are the effects of NO2 (on natural
      mortality), mostly associated with traffic emissions, and of PM2.5 (on cardiac
      and respiratory mortality). Nitrogen dioxide shows an independent effect from the
      particulate matter, as observed in the bi-pollutant models.

PMID- 24293492
TI  - [A screening and comprehensive assessment programme aimed at secondary prevention
      of disability in community-dwelling frail older subjects: a pilot study].
AB  - OBJECTIVE: to test a screening and comprehensive assessment procedures for frail
      elderly in Tuscany (Central Italy) in the perspective of interventions to prevent
      disability. DESIGN: two-phases feasibility study: a) screening phase, using a
      postal questionnaire and b) comprehensive assessment phase, aimed at identifying
      risk factors for disability that might be targeted by specific interventions.
      SETTING AND PARTICIPANTS: 11,589 individuals aged over 70, living at home,
      identified from residents registry of 2 health care districts in Tuscany,
      excluding subjects with recognized disability and those living in nursing home.
      Participants were sent a 7-item postal questionnaire (modified Sherbrooke Postal
      Questionnaire). Respondents with a score =3, suggestive of frailty, were offered
      an in-home comprehensive assessment performed by a nurse or social worker,
      oriented to ascertain independence in activities of daily living, lower limbs
      extremity function, mood status, malnutrition risk, cognitive level, visual
      acuity, hearing function, environmental risk and medications number. General
      practitioners, social workers or specific health care services were thereafter
      informed about results of the assessment with recommendations for specific
      interventions. RESULTS: among 6,629 respondents to the questionnaire, 52% (No.
      3,432) scored =3, triggering the comprehensive assessment, which was performed in
      66% of cases (No. 2,276). Out of them, 38% showed already a disability in basic
      activities of daily living. Of the remaining 1,411, 38% showed a disability in
      instrumental activities of daily living, 30% a reduced lower limb extremity
      function, 18% depressive symptoms, and 11% a cognitive impairment. Human
      resources used for the project were limited in relation to the extent of the
      involved population. CONCLUSIONS: postal screening of frailty in older subjects
      is feasible and is able to identify patients who might benefit from further
      assessment to address interventions for specific risk factors.

PMID- 24293491
TI  - [Volumes of services supplied by Italian Stop-Smoking Services and their
      characteristics predictive of abstinence].
AB  - OBJECTIVE: to evaluate differences in terms of smokers' attendance to National
      Health System (NHS) Stop-Smoking Services with a prevalent individual approach
      (SSSi), and to those with a prevalent group approach (SSSg). To identify
      predictive characteristics of success, in terms of quit rates at the end of
      treatment (QR0) and after 6 months (QR1), according to SSS type (SSSi/SSSg),
      treatment (individual/ group counseling with/without pharmacologic treatments), 5
      SSS scores: type of structure (S), number and hours per week of SSS health
      professionals (P), SSS involvement in local tobacco control networks (N), and
      type of smokers' assessment (A); and 3 principal components of SSS
      characteristics. DESIGN: survey to 19 SSSs, and survey to smokers attending these
      SSSs, with a six month follow-up. SETTING AND PARTICIPANTS: 1,276 smokers
      attending 19 SSSs (664 at 7 SSSi; 612 at 12 SSSg) in 9 months in the period 2008
      2010. MAIN OUTCOME MEASURES: smokers' attendance to scheduled sessions; QR0; QR1.
      RESULTS: even though SSSi treated more smokers per month (12 vs. 8 in SSSg), SSSi
      scheduled fewer treatment sessions (7 vs. 9 sessions) in a wider treatment period
      (3 months vs. 2 in SSSg). SSSg recorded lower P and higher A scores. Four out of
      5 smokers attending SSSg and 2/5 of smokers attending SSSi completed treatment
      protocols. Considering all smokers, QR1 in both types of SSS were around 36%.
      Smokers treated with pharmacotherapy, those more motivated and with high self
      efficacy, and those non-living together with smokers were more likely to recorded
      higher QR1. CONCLUSIONS: the most relevant interventions in order to increase the
      number of smokers treated at SSS and to improve cessation rates among them were:
      for SSSi, increasing completion to treatment protocol; for SSSg, improving the P
      scores to increase the number of treated smokers; for all SSS, increasing the use
      of pharmacotherapy in combination with individual/group counseling to sustain
      abstinence.

PMID- 24293488
TI  - [Air pollution and urgent hospital admissions in 25 Italian cities: results from
      the EpiAir2 project].
AB  - OBJECTIVE: to evaluate the relationship between air pollution and hospital
      admissions in 25 Italian cities that took part in the EpiAir (Epidemiological
      surveillance of air pollution effects among Italian cities) project. DESIGN:
      study of time series with case-crossover methodology, with adjustment for
      meteorological and time-dependent variables. The association air pollution
      hospitalisation was analyzed in each of the 25 cities involved in the study; the
      overall estimates of effect were obtained subsequently by means of a meta
      analysis. The pollutants considered were PM10, PM2.5 (in 13 cities only), NO2 and
      ozone (O3); this last pollutant restricted to the summer season (April
      September). SETTING AND PARTICIPANTS: the study has analyzed 2,246,448 urgent
      hospital admissions for non-accidental diseases in 25 Italian cities during the
      period 2006- 2010; 10 out of 25 cities took part also in the first phase of the
      project (2001-2005). MAIN OUTCOME MEASURES: urgent hospital admissions for
      cardiac, cerebrovascular and respiratory diseases, for all age groups, were
      considered. The respiratory hospital admissions were analysed also for the 0-14
      year subgroup. Percentage increases risk of hospitalization associated with
      increments of 10 ug/m(3) and interquartile range (IQR) of the concentration of
      each pollutant were calculated. RESULTS: reported results were related to an
      increment of 10 ug/m(3) of air pollutant. The percent increase for PM10 for
      cardiac causes was 0.34% at lag 0 (95%CI 0.04-0.63), for respiratory causes 0.75%
      at lag 0-5 (95%CI 0.25-1.25). For PM2.5, the percent increase for respiratory
      causes was 1.23% at lag 0- 5 (95%CI 0.58-1.88). For NO2, the percent increase for
      cardiac causes was 0.57% at lag 0 (95%CI 0.13-1.02); 1.29% at lag 0-5 (95%CI 0.52
      2.06) for respiratory causes. Ozone (O3) did not turned out to be positively
      associated neither with cardiac nor with respiratory causes as noted in the
      previous period (2001-2005). CONCLUSION: the results of the study confirm an
      association between PM10, PM2.5, and NO2 on hospital admissions among 25 Italian
      cities. No positive associations for ozone was noted in this period.

PMID- 24293489
TI  - [Policies for the promotion of sustainable mobility and the reduction of traffic
      related air pollution in the cities participating in the EpiAir2 project].
AB  - OBJECTIVE: to describe transport policies adopted in recent years (2006-2010) by
      some Italian municipalities and their effectiveness. DESIGN AND SETTING: survey
      data refer to fifteen cities participating in the EpiAir2 project: Torino,
      Milano, Venezia, Bologna, Firenze, Pisa, Roma, Taranto, Palermo, Cagliari,
      Trieste, Genova, Ancona, Napoli, and Bari. RESULTS: this survey revealed
      strengths and weaknesses of the way in which these Italian cities address the
      promotion of sustainable mobility. As a general rule, the vehicle fleets have
      been renewed with a reduction of old-emission-standard vehicles. Italian cities
      reported a considerable delay in the development of underground and tram systems,
      and suburban rail networks, compared to other European urban areas. Regarding
      other aspects of urban mobility (supply/demand for public transport, low traffic
      and pedestrian zones, bike paths, car and bike sharing), this survey highlighted
      a great heterogeneity among Italian cities. CONCLUSION: differences between
      Italian cities are partly explained by structural and cultural features and also
      by local governance, specifically the political capability to design and adopt
      effective policies concerning urban transportation systems and their
      environmental impact. Various and fragmented initiatives are signs that Italy has
      not formulated a comprehensive and integrated strategy about sustainable mobility
      in urban areas yet.

PMID- 24293493
TI  - [Using hospital discharge records, birth certificates and a birth defects
      registry for epidemiological and public health purposes: experience in Emilia
      Romagna region (northern Italy)].
AB  - OBJECTIVES: implementation and validation of a methodology to link and integrate
      hospital discharge record (SDO), birth certificate (CeDAP) and the population
      based registry of congenital malformations of the Emilia-Romagna Region (IMER).
      An algorithm has been developed to link registry data and administrative data
      through the use of indirect patient identifiers in order to exploit the strengths
      of the different data sources and to expand the pool of existing data available
      for the analysis. DESIGN: use of IMER Registry, birth certificates and hospital
      discharge records to assess and diagnose congenital malformations; these data
      sources vary in terms of availability and accuracy. SETTING AND PARTICIPANTS:
      data from IMER Registry, SDO and CeDAP for year 2009 have been used. RESULTS: the
      main results of the study are: 1. a perfect monitoring system does not exist, the
      algorithm proposed enabled the integration of three different sources and the
      evaluation of the capacity to identify different anomalies to be capitalized on;
      2. the high number of false positives in audit reporting in 4 hospitals
      underlines the importance of the contribution of clinical experts in the review
      of the case to exclude coding errors, clarify unspecific diagnostic categories
      and identify syndromes; 3. the IMER Registry with over 30 years of experience has
      been the catalyst for this work by integrating clinical skills in the registry
      with the public health expertise of other professionals involved in information
      flows; 4. in the absence of a single comprehensive source of data collection, the
      advantage of the integration of the information collected from multiple sources
      is confirmed. CONCLUSION: birth defects surveillance programmes are critical
      resources that can provide fundamental information to take sound decisions in
      healthcare planning and for environmental epidemiology studies. This experience,
      whilst not mechanically transferable to other areas and circumstances, is a model
      for the future clinical and epidemiological management of congenital anomalies.

PMID- 24293490
TI  - [Short-term impact of air pollution among Italian cities covered by the EpiAir2
      project].
AB  - OBJECTIVES: to estimate the short-term impact of air pollutants on adult
      population of 23 Italian cities on the calendar period 2006- 2009 as part of the
      EpiAir2 project. DESIGN, MATERIALS AND METHODS: for each city, the short-term
      impact of air pollution on mortality was estimated. In particular, it was
      calculated the number of deaths attributable to particulate matter levels (PM10
      and PM2.5) exceeding different thresholds deriving from the European Union
      legislation and the World Health Organization guidelines (PM10: 20 and 40
      ug/m(3), reduction of 20% up to 20 ug/m(3) and more than 35 days per year with
      daily average above 50 ug/m(3); PM2.5: 10, 18 and 25 ug/m(3), reduction of 20% up
      to 18 ug/m(3)). The impact evaluation was done combining the effect estimates of
      air pollutant, the observed mortality level and the air pollution concentration
      measured by the ambient monitors. Regarding effects, the posterior city-specific
      distributions arising from a Bayesian metanalysis was employed. Uncertainty
      around the impact estimates was obtained by Monte Carlo methods. RESULTS:
      overall, in the 23 cities considered in the present study attributable deaths to
      short-term effects of PM10 concentrations above 20 ug/m(3) as annual average and
      of PM2.5 concentrations above 10 ug/m(3) on the period 2006-2009 was respectively
      0.9% (assuming independence among cities the 80% credibility interval is 0.4-1.4)
      and 0.8% (80%CrI 0.2-1.3) of natural mortality. The impact was larger for the
      cities of the river Po valley, the Florence area and the large conurbations of
      Rome, Naples and Palermo: considering PM10 1.0% (80%CrI 0.4-1.5) vs. 0.4% (80%CrI
      0.2-0.7) of natural deaths among the other cities in the study. Pollution
      reduction actions as prescribed by the European Union legislation, i.e. a 20%
      reduction up to 20 ug/m(3) for PM10 and up to 18 ug/m(3) for PM2.5, would have
      saved, over all the cities covered by this study, 42% and 51% of all attributable
      deaths, respectively. CONCLUSIONS: during the study period, air pollution
      exposure was responsible for a relevant impact on mortality in the enrolled
      cities. Policies based on percent reduction of PM10 and PM2.5 as prescribed by
      the European Union could substantially reduce the short term impact on population
      mortality.

PMID- 24293494
TI  - [Information on educational level from hospital discharge register: an analysis
      of validity].
AB  - OBJECTIVE: to analyze the validity of information on educational level from
      Hospital discharge register, by comparison with the 2001 Census; to develop a
      hierarchical algorithm which allows to maximize its validity. METHODS: Hospital
      Information System (HIS) of Lazio Region and 2001 Census were used to select all
      the hospital admissions between 2000 and 2009 of at least 35-year-old people
      living in Rome and registered at 2001 Census. For each hospitalisation, the
      information on education stated on Census was associated. Agreement with Census
      was measured using Cohen's kappa. A hierarchical algorithm based on the results
      of agreement analysis was developed. For each patient, it selects the most valid
      admission in order to find the most accurate information on education. The
      application of the algorithm was tested on four cohorts of 2008-2009 hospital
      admissions. RESULTS: a good agreement on education from HIS and Census (k between
      0.5 and 0.6) was found. The information on education was better for planned
      hospitalisations placed in hospitals with a volume of care within the 12,000
      admissions per year. The agreement between HIS and Census in hip fractures and
      acute myocardial infarction cohorts was considered sufficient (k=0.3), while it
      was found a good/excellent agreement in cholecystectomy and coronary artery
      bypass (k=0.6 for both conditions) cohorts. The application of the algorithm to
      the cohorts of acute care hospitalisations allowed moving to a level of good
      agreement (increase: 19%). The gain was much lower in the elective admission
      cohorts (4%). CONCLUSIONS: the overall agreement is good, but it depends on the
      characteristics of the hospital admission. However, these differences may be
      reduced by using hierarchical algorithm.

PMID- 24293496
TI  - [Focus on electronic cigarettes].
AB  - There is no clear regulation on electronic cigarettes (e-cig); their health
      effects are not yet fully investigated and there is insufficient standardisation
      and quality control of the product. Moreover, the e-cig could be a gateway for
      young people to nicotine addiction and traditional cigarette smoking. In Italy,
      the Ministry of Health banned the sale of e-cig with nicotine firstly to
      adolescents aged <16 years, then to people <18 years. Until further scientific
      evidence is available, it is mandatory to regulate the production and marketing
      of e-cigs, to make them less attractive, to forbid their use in enclosed areas,
      and prevent them from being promoted. E-cigs, however, seem to be much less
      dangerous than traditional cigarettes, although the few studies conducted are not
      sufficient to demonstrate either a clear therapeutic efficacy of e-cig or their
      total harmlessness. If e-cig had a known content, were made according to clear
      rules and in certified laboratories, without toxic substances, it could be used
      to help heavy smokers to quit, or at least to reduce smoking habits. There is a
      large proportion of smokers who are unable to quit. The revision of the European
      Directive (the proposal is being evaluated and we are waiting for its final
      approval) on tobacco recommends free sale for a minority of e-cigs only, those
      with a nicotine content <4 mg/ml. This will be difficult, considering that the
      business is just the free sale of e-cig and the much more dangerous tobacco
      cigarettes are still sold without any restriction. 

PMID- 24293495
TI  - [Interrater reliability of the Bayley III test in the Italian Northern-Adriatic
      Cohort II].
AB  - OBJECTIVE: to assess the agreement between two trained psychologists who
      administered the Bayley Scale of Infant Development III (BSID III) to detect
      neurodevelopment deficits in a cohort of children within the Northern Adriatic
      Cohort II (NAC II) longitudinal study, which aims to assess the impact of mercury
      exposure through food consumption of mothers in pregnancy on their children's
      neurodevelopment. DESIGN: a reliability study was carried out. Two trained
      psychologists administered the test, each one scoring the test independently, and
      serving as the primary examiner for half of the sample and as the observer for
      the other half. SETTING AND PARTICIPANTS: a sample of 53 children of 18 months of
      age was enrolled consecutively within the Italian NAC II, and tested using the
      Bayley Scale of Infant Development III (BSID III) to detect neurodevelopment
      deficits. MAIN OUTCOME MEASURES: the cognitive, language, and motor scales of the
      BSID III were evaluated and the respective Intraclass Correlation Coefficients
      (ICC) were calculated. RESULTS: overall, the ICCs for the cognitive and language
      scales were very high (>=0.98), while the ICCs for the motor scales were slightly
      lower, ranging from 0.86 (gross motor, scaled) to 0.97 (fine motor, scaled), but
      still higher than 0.80, reported as the general acceptable benchmark for
      psychological testing. CONCLUSION: the interrater reliability of all BSID III
      scales for this sample of 18-month-old children is very high and assures
      comparable results between the two psychologists involved in the Italian NAC II
      study. The reasons are a common training, the joint evaluation of many children
      during the preliminary phase of the study, the discussion of inconsistent
      results, but also the "go no-go" nature of the items in BSID III.

PMID- 24293497
TI  - [Routine health statistics are unknown].
AB  - Caesarean section is a topic of particular attention and interest both for woman
      and newborn health, and for its economic implications. Unfortunately, there is
      inadequate information arising from Certificates of Attendance at Birth and
      Nosological Cards Discharge Hospital, in order to enable possible measures for
      reducing the excess of caesarean section as an alternative method to vaginal
      delivery. Moreover, the existing current health surveys do not distinguish
      properly between the various reasons of performing caesarean section, and do not
      provide a correct and exhaustive framework of the collateral aspects of this
      practice and the dramatic consequences which may result from maneuvers, such as
      manual fundal pressures, performed during delivery. Further investigations
      confirm the presence of unexplained, and therefore unjustifiable, discrepancies. 

PMID- 24293499
TI  - [Consensus conference: should breast cancer screening be tailored to selected
      risk factors?].

PMID- 24293498
TI  - [Tailored Breast Screening Trial (TBST)].
AB  - BACKGROUND: mammography screening in premenopausal women is still the object of
      controversy and the cost and harms-benefit balance is lower than the one observed
      for women aged 50 years or more. The reasons are the lower screening sensitivity
      and the lower risk of occurrence of breast cancer at younger ages. For these
      reasons, an annual interval is suggested for this age group, and a lower positive
      predictive value of the recall rate is observed in screening practice. Harms of
      screening are false positive rates and overdiagnosis (that is an exceeding number
      of cases over the women's lifetime ascribable to early diagnosis). A tailored
      approach to screening could both contribute to a reduction of possible harms and
      reduce the costs of the service screening programmes, which started to offer
      screening mammography to 45- 49-year-old women also in Italy, according with the
      suggestions of the Italian Group for Mammography Screening. Higher breast density
      is considered a marker of risk and, at the same time, it brings about a masking
      effect that decreases the screening mammography sensitivity at younger ages. AIM:
      the Tailored Breast Screening Trial (TBST) is a population-based, non-inferiority
      randomised trial aimed at evaluating the impact of a change in the screening
      protocol in a service screening practice. "Tailored" means that the use of a
      breast density classification allocates women to a longer interval, decreasing
      the number of screening rounds in the 45- 50-year age range. Density of the
      breast at the baseline is considered as an indicator of risk and also as a
      masking factor. The aim of this study is to assess the impact of a longer
      interval and the reduction of side effects for women allocated to the
      intervention group. In this study, any further intervention is offered to high
      density women who are followed-up according to the usual care interval, since the
      study aimed at decreasing the screening burden. METHODS: 45-year-old women
      resident in the screening centre catchment area will be invited to attend for
      mammography screening and will be asked for informed consent in order to be
      included in the study. After the enrolment, they will receive a high quality
      digital mammography; two views and breast density will be classified according
      with the BI-RADS classification. Women are randomly allocated either to an usual
      care group or to the intervention group. In the intervention group, women with a
      dense breast (3-4 categories in BI-RADS)will be invited again after 1 year, while
      the lower-density group in the intervention arm will be invited after 2 years.
      After the age of 50, all women will continue to be screened in the usual service
      screening programme. Density of the breast will be read by 2 readers, and
      controversies will be solved by a consensus. Allocation of women is blinded to
      the mammography readers. EXPECTED RESULTS: the outcomes are: A. cumulative
      incidence of interval-cancer cases by intention to treat (ITT) grouping and by
      density group, aimed at assessing the non inferiority of screening performance;
      B. cumulative incidence of T2+/node-positive status breast cancer cases between
      arms and by protocol. Screening performance parameters will be evaluated at each
      screening round. Interim and outcome analysis are expected at 3 and 6 years
      average follow- up, respectively, starting from the beginning of the screening.
      SAMPLE SIZE: the non-inferiority limit is derived from the accepted level of
      interval cancers in women 50-69 years, which was considered acceptable by the
      European Community Guidelines. Assuming a 70%BI-RADS 1-2 at the baseline on the
      basis of the digital mammography experience, the estimated sample size with a
      power of 90% is 16,596 women per arm. RESULTS OF THE FEASIBILITY STUDY: the
      background of the study, that uses data from cancer registries and screening
      centres, describes the most relevant characteristics of breast cancer occurring
      in the Italian regions where the study will be conducted. The description of
      stage distribution in the 40-54-year-old group and the coverage by spontaneous
      screening, as available by outpatient current data, showed the modification of
      stage at presentation, according with the implementation of service screening in
      women 50-54 years. In Emilia-Romagna and Piedmont Regions, service screening is
      already active for women aged 45 years and more, even though different invitation
      protocols were used. In Tuscany Region the extension of screening has already
      been planned for the next few years. Performance data are reported: they show the
      recall and the detection rates at first and at repeated screening rounds in
      Emilia-Romagna Region. In order to assess the feasibility and the interobserver
      reproducibility of breast density visual classification by BI-RADS, two testing
      sets of 80 digital mammograms for screened women aged 50-52 years were made
      available by the ISPO (Institute for oncological study and prevention) service
      screening tests. The test was performed by 11 radiologists, which are members of
      the working group. Concordance was moderate with a BI-RADS classification in 4
      categories (kappa=0.46;95%CI 0.41-0.53), and substantial using 1-2 vs.3-4
      (kappa=0.68;95%CI 0.59-0.79). The retest performed using the second mammography
      test did not change the results. CONCLUSION: the TBST was authorised by the
      Ethical Committee in Florence (Tuscany Region, Central Italy) and the recruitment
      is still in progress through the invitation of the target population in the
      participating screening centres. In Florence and Veneto Region, the first round
      is almost completed and it confirmed the feasibility of the study and of the
      randomisation process.

PMID- 24293500
TI  - [Identical yet different twins].

PMID- 24293503
TI  - Relevance of hospital characteristics as performance indicators for treatment of
      very-low-birth-weight neonates.
AB  - BACKGROUND: Current attempts at centralization of neonatal care in Germany focus
      on a minimum volume of 30 very-low-birth-weight (VLBW, weighing <1250 g) neonate
      admissions per year. However, the evidence for a selective referral strategy
      based on hospital volume is unclear. METHOD: A total of 5575 neonates weighing
      <1250 g treated in 31 hospitals in Bavaria between 2000 and 2011 were analysed
      using population-based data. The relevance of different hospital characteristics
      (i.e. hospital volume, bed capacity and teaching status) for explaining
      individual in-hospital mortality as well as interhospital variation in mortality
      rates was analysed using multilevel logistic regression analysis. RESULTS: In a
      risk-adjusted model, only dichotomized hospital volume (<30 admissions) was
      significantly associated with higher mortality in VLBW neonates (odds ratio:
      1.74; 95% confidence interval: 1.02-2.99). However, the higher mortality risk
      only applied to neonates with higher Clinical Risk Index for Babies (CRIB)
      scores. There was considerable heterogeneity in mortality rates between Bavarian
      hospitals. The median odds ratio for mortality between two neonates treated in a
      randomly chosen low-performing versus high-performing hospital was 1.62 in the
      null model (without explanatory variables). Hospital volume only explained 15.1%
      of interhospital variation in mortality rates after adjustment for case-mix.
      Other hospital characteristics were of minor relevance. A funnel plot of the
      standardized mortality ratio against the number of admissions showed that 41% of
      small-volume hospitals performed better than expected. CONCLUSION: A selective
      referral strategy based solely on hospital volume will fall short of the task of
      optimal allocation of neonatal care by means of centralization.

PMID- 24293504
TI  - Sleep problems, exercise and obesity and risk of chronic musculoskeletal pain:
      the Norwegian HUNT study.
AB  - BACKGROUND: The objective was to investigate the association between self
      reported sleep problems and risk of chronic pain in the low back and
      neck/shoulders, and whether physical exercise and body mass index (BMI) alter
      this association. METHODS: The study comprised data on 26 896 women and men in
      the Nord-Trondelag Health Study (Norway) without chronic pain or physical
      impairment at baseline in 1984-86. Occurrence of chronic pain was assessed at
      follow-up in 1995-97. A generalized linear model was used to calculate adjusted
      risk ratios. RESULTS: Sleep problems were dose-dependently associated with risk
      of pain in the low back and neck/shoulders in both women and men (P < 0.001 both
      genders). Women and men who reported sleep problems 'sometimes' and
      'often/always' had a higher risk of chronic pain of 23-32% and 51-66%,
      respectively, than those who reported sleep problems 'never'. Combined analyses
      showed that persons with sleep problems 'sometimes' and who exercised >=1 hour
      per week had lower risk of chronic pain in the low back (P < 0.04) and
      neck/shoulders (P < 0.001) than inactive persons with a similar level of sleep
      problems (P < 0.04). Likewise, persons with BMI <25 kg/cm(2) and sleep problems
      'sometimes' had lower risk of chronic pain in the low back (P < 0.001) and
      neck/shoulders (P < 0.001) than persons with BMI >=25 kg/cm(2) and a similar
      level of sleep problems. CONCLUSION: Sleep problems are associated with an
      increased risk of chronic pain in the low back and neck/shoulders. Regular
      exercise and maintenance of normal body weight may reduce the adverse effect of
      mild sleep problems on risk of chronic pain.

PMID- 24293505
TI  - How might the alcohol minimum unit pricing (MUP) impact upon local off-sales
      shops and the communities which they serve?
AB  - AIMS: The aim of the study was to assess the likely impact of the Scottish
      Government's proposed alcohol minimum unit pricing (MUP) policy on community off
      sales outlets (convenience stores or corner shops), and, in turn, on the local
      people who purchase drinks at such premises. This research adds to our knowledge
      by linking sales of alcohol products which will be affected by MUP (e.g. at the
      proposed 50 ppu) to the types of communities where these are the 'drinks-of
      choice'. METHODS: A survey of independent community off-sales operating within
      the city of Glasgow, Scotland (n = 271) returned 144 completed questionnaires
      enquiring about each shop's customer base, best-selling alcohol products and
      participating shopkeepers' views on MUP. Responses were measured against current
      alcohol product prices (i.e. whether potentially affected by MUP) and local
      levels of socio-economic deprivation. RESULTS: Participating shopkeepers were
      divided in their support for MUP, although more were in favour than against.
      Support for MUP tended to be rooted in business concerns. A majority reported
      having at least one best-selling alcohol product which will be affected by the
      proposed MUP policy at current prices, with the beverages that would be most
      affected (e.g. white cider) tending to be best-sellers at shops serving deprived
      communities. CONCLUSION: MUP is likely to impact most in socio-economically
      deprived communities. This is also where alcohol-related health and other
      inequalities are currently greatest.

PMID- 24293506
TI  - Exposure of children and adolescents to alcohol marketing on social media
      websites.
AB  - AIMS: In 2011, online marketing became the largest marketing channel in the UK,
      overtaking television for the first time. This study aimed to describe the
      exposure of children and young adults to alcohol marketing on social media
      websites in the UK. METHODS: We used commercially available data on the three
      most used social media websites among young people in the UK, from December 2010
      to May 2011. We analysed by age (6-14 years; 15-24 years) and gender the reach
      (proportion of internet users who used the site in each month) and impressions
      (number of individual pages viewed on the site in each month) for Facebook,
      YouTube and Twitter. We further analysed case studies of five alcohol brands to
      assess the marketer-generated brand content available on Facebook, YouTube and
      Twitter in February and March 2012. RESULTS: Facebook was the social media site
      with the highest reach, with an average monthly reach of 89% of males and 91% of
      females aged 15-24. YouTube had a similar average monthly reach while Twitter had
      a considerably lower usage in the age groups studied. All five of the alcohol
      brands studied maintained a Facebook page, Twitter page and YouTube channel, with
      varying levels of user engagement. Facebook pages could not be accessed by an
      under-18 user, but in most cases YouTube content and Twitter content could be
      accessed by those of all ages. CONCLUSION: The rise in online marketing of
      alcohol and the high use of social media websites by young people suggests that
      this is an area requiring further monitoring and regulation.

PMID- 24293507
TI  - Pathophysiology of human heart failure: importance of skeletal muscle myopathy
      and reflexes.
AB  - In the last 20 years there has been mounting evidence that chronic heart failure
      (CHF) has a complex pathophysiology, which begins with an abnormality of the
      heart as a 'primum movens', but involves adaptive changes in many body parts,
      including the cardiovascular, musculoskeletal, renal, neuroendocrine,
      haemostatic, immune and inflammatory systems. Alterations in skeletal muscle are
      also of importance in limiting functional capacity in patients with CHF, because
      reduced physical activity plays some part in the muscle alterations in CHF. On
      the whole, these abnormalities resemble those induced by physical deconditioning.
      Moreover, the overactivation of signals originating from skeletal muscle
      receptors (mechano-metaboreceptors) is an intriguing hypothesis proposed to
      explain the origin of symptoms and the beneficial effect of exercise training in
      the CHF syndrome. These reflexes may contribute to sympathetic overactivation, to
      exercise intolerance and to the progression of CHF syndrome. The so-called
      metaboreflex has been reported to be hyperactive in CHF and to be responsible for
      a paradoxical increase in systemic vascular resistance and decrease in cardiac
      output whenever activated in these patients. This report is a brief summary of
      the latest news in this area of research. 

PMID- 24293508
TI  - Dual contraceptive use among adolescents and young adults: correlates and
      implications for condom use and sexually transmitted infection outcomes.
AB  - BACKGROUND: Simultaneous condom and hormonal contraception usage ('dual method
      use') maximises protection against pregnancy and sexually transmitted infection
      (STI), although there is concern that promotion of this strategy could result in
      diminished condom use and inadvertently increase STI risk. In this study, we (1)
      assessed how the use of dual methods, versus condoms alone, related to STI and
      consistency of condom use and (2) described the correlates of dual use. METHODS:
      A sample of 1450 young people aged 12-25 years were surveyed and screened for
      chlamydia and gonorrhoea at non-clinical sites in two high morbidity Californian
      counties in 2002-2003. Differences in STI prevalence and reported consistency of
      condom use were assessed for 'condom only' and 'dual method' users. Correlates of
      dual use were analysed via multivariate polytomous logistic regression. RESULTS:
      Condom only and dual method users did not significantly differ in terms of STI
      prevalence or reported consistency of condom use. Sex, age, race and relationship
      tenure were significant correlates of dual use. DISCUSSION: In these
      observational data, dual method use did not detrimentally affect STI risk. If
      interpreted alongside each subgroups' risk patterns for STI and unplanned
      pregnancy, the correlates of dual use can inform STI and pregnancy prevention
      interventions.

PMID- 24293516
TI  - Long-term cognitive and functional effects of potentially inappropriate
      medications in older women.
AB  - BACKGROUND: The use of potentially inappropriate medications in older adults can
      lead to known adverse drug events, but long-term effects are less clear. We
      therefore conducted a prospective cohort study of older women to determine
      whether PIM use is associated with risk of functional impairment or low cognitive
      performance. METHODS: We followed up 1,429 community-dwelling women (>= 75 years)
      for a period of 5 years at four clinical sites in the United States. The primary
      predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed
      anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes
      included scores on a battery of six cognitive tests at follow-up and having one
      or more incident impairments in instrumental activities of daily living.
      Regression models were adjusted for baseline age, race, education, smoking,
      physical activity, a modified Charlson Comorbidity Index, and cognitive score.
      RESULTS: The mean +/- SD age of women at baseline was 83.2 +/- 3.3. In
      multivariate models, baseline PIM use and higher ACB scores were significantly
      associated with poorer performance in category fluency (PIM: p = .01; ACB: p =
      .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p =
      .04). Both PIM use (odds ratio [OR]: 1.36 [1.05-1.75]) and higher ACB scores (OR:
      1.11 [1.04-1.19]) were also strongly associated with incident functional
      impairment. CONCLUSIONS: The results provide suggestive evidence that PIM use and
      increased anticholinergic load may be associated with risk of functional
      impairment and low cognitive performance. More cautious selection of medications
      in older adults may reduce these potential risks.

PMID- 24293518
TI  - BACs to the future: new genetic models for cardiovascular discovery.

PMID- 24293517
TI  - Loss of ATE1-mediated arginylation leads to impaired platelet myosin
      phosphorylation, clot retraction, and in vivo thrombosis formation.
AB  - Protein arginylation by arginyl-transfer RNA protein transferase (ATE1) is
      emerging as a regulator protein function that is reminiscent of phosphorylation.
      For example, arginylation of beta-actin has been found to regulate lamellipodial
      formation at the leading edge in fibroblasts. This finding suggests that similar
      functions of beta-actin in other cell types may also require arginylation. Here,
      we have tested the hypothesis that ATE1 regulates the cytoskeletal dynamics
      essential for in vivo platelet adhesion and thrombus formation. To test this
      hypothesis, we generated conditional knockout mice specifically lacking ATE1 in
      their platelets and in their megakaryocytes and analyzed the role of arginylation
      during platelet activation. Surprisingly, rather than finding an impairment of
      the actin cytoskeleton structure and its rearrangement during platelet
      activation, we observed that the platelet-specific ATE1 knockout led to enhanced
      clot retraction and in vivo thrombus formation. This effect might be regulated by
      myosin II contractility since it was accompanied by enhanced phosphorylation of
      the myosin regulatory light chain on Ser19, which is an event that activates
      myosin in vivo. Furthermore, ATE1 and myosin co-immunoprecipitate from platelet
      lysates. This finding suggests that these proteins directly interact within
      platelets. These results provide the first evidence that arginylation is involved
      in phosphorylation-dependent protein regulation, and that arginylation affects
      myosin function in platelets during clot retraction. 

PMID- 24293519
TI  - Acetylation of cyclophilin A is required for its secretion and vascular cell
      activation.
AB  - AIMS: Cyclophilin A (CyPA) is a pro-inflammatory mediator involved in oxidative
      stress-related cardiovascular diseases. It is secreted from vascular smooth
      muscle cell (VSMC) in response to reactive oxygen species (ROS) in a highly
      regulated manner. Extracellular CyPA activates VSMCs and endothelial cells (ECs)
      promoting inflammation, cell growth, and cell death. Recently, it was shown that
      acetylated CyPA (AcK-CyPA) affects its function. We investigated the role of
      acetylation of CyPA for its secretion and signalling in vascular cells. METHODS
      AND RESULTS: We used angiotensin II (Ang II) to create sustained ROS and found
      significantly increased AcK-CyPA in VSMC. Site-directed mutagenesis showed that
      lysines K82 and K125 were the predominant CyPA residues acetylated in response to
      Ang II. Importantly, acetylation of K82 and K125 were required for Ang II
      mediated CyPA secretion. ROS inhibitors, Tiron, and N-acetylcysteine inhibited
      Ang II-induced intracellular CyPA acetylation and also AcK-CyPA secretion. Using
      secreted CyPA from wild type and K82/125R mutants expressed in transduced VSMC or
      in vitro acetylated recombinant CyPA, we showed that extracellular AcK-CyPA
      significantly increased pERK1/2, matrix metalloproteinase-2 activation, and ROS
      production in VSMC compared with non-acetylated CyPA. Moreover, extracellular AcK
      CyPA increased adhesion molecule expression (VCAM-1 and ICAM-1) in EC, which
      promoted monocyte adhesion. CONCLUSIONS: ROS-dependent acetylation of CyPA is
      required for the generation of extracellular CyPA. Acetylated extracellular CyPA
      regulates VSMC and EC activation, suggesting that inhibition of acetylation of
      CyPA may prevent the pathogenesis of oxidative stress-related cardiovascular
      diseases.

PMID- 24293520
TI  - Acute chest pain and massive LV hypertrophy in a 38-year-old man.

PMID- 24293521
TI  - Risk stratification in adults with repaired tetralogy of fallot: the long journey
      from clinical parameters and surface ecg to in-depth assessment of myocardial
      mechanics, volume and pressure loading.

PMID- 24293522
TI  - Progress: the ROPAC multinational registry advances our understanding of an
      important outcome in pregnant women with heart disease.

PMID- 24293523
TI  - Heart failure in pregnant women with cardiac disease: data from the ROPAC.
AB  - OBJECTIVE: Heart failure (HF) is one of the most important complications in
      pregnant women with heart disease, causing maternal and fetal mortality and
      morbidity. METHODS: This is an international observational registry of patients
      with structural heart disease during pregnancy. Sixty hospitals in 28 countries
      enrolled 1321 women between 2007 and 2011. Pregnant women with valvular heart
      disease, congenital heart disease, ischaemic heart disease, or cardiomyopathy
      could be included. Main outcome measures were onset and predictors of HF and
      maternal and fetal death. RESULTS: In total, 173 (13.1%) of the 1321 patients
      developed HF, making HF the most common major cardiovascular complication during
      pregnancy. Baseline parameters associated with HF were New York Heart Association
      class >= 3, signs of HF, WHO category >= 3, cardiomyopathy or pulmonary
      hypertension. HF occurred at a median time of 31 weeks gestation (IQR 23-40) with
      the highest incidence at the end of the second trimester (34%) or peripartum
      (31%). Maternal mortality was higher in patients with HF (4.8% in patients with
      HF and 0.5% in those without HF p<0.001). Pre-eclampsia was strongly related to
      HF (OR 7.1, 95% CI 3.9 to 13.2, p<0.001). Fetal death and the incidence of
      preterm birth were higher in women with HF compared to women without HF (4.6% vs
      1.2%, p=0.001; and 30% vs 13%, p=0.001). CONCLUSIONS: HF was the most common
      complication during pregnancy, and occurred typically at the end of the second
      trimester, or after birth. It was most common in women with cardiomyopathy or
      pulmonary hypertension and was strongly associated with pre-eclampsia and an
      adverse maternal and perinatal outcome.

PMID- 24293524
TI  - Understanding partial protection and HIV risk and behavior following voluntary
      medical male circumcision rollout in Kenya.
AB  - In the midst of scaling up voluntary medical male circumcision (VMMC) in Kenya,
      there is concern that men do not adequately understand that circumcision provides
      only partial protection against HIV. The study goal was to determine men's
      understanding of partial protection, perceptions of HIV risk before and after
      VMMC and use of protective measures following VMMC. In-depth interviews with 44
      men aged 18-39 years recently circumcised or planning to undergo VMMC were
      conducted in two urban and rural districts in Nyanza Province, Kenya.
      Participants described partial protection as the need to continue using other HIV
      protective measures such as condoms, with numbers such as a '60 percent
      protection' or 'not 100 percent protection', and described how circumcision
      reduces HIV transmission such as reduced penile bruising or bleeding. Most said
      their HIV risk before VMMC was high and that VMMC would reduce their risk
      moderately. Participants demonstrated good understanding of partial protection
      and there was little suggestion of risk compensation following VMMC. 

PMID- 24293525
TI  - CrossTalk proposal: Guyton's venous return curves should be taught.

PMID- 24293526
TI  - CrossTalk opposing view: Guyton's venous return curves should not be taught.

PMID- 24293527
TI  - Rebuttal from Philip Andrew.

PMID- 24293528
TI  - Rebuttal from Daniel Beard and Eric Feigl.

PMID- 24293529
TI  - Nanotechnology tracks to the renal ward.

PMID- 24293530
TI  - Hypertension: is it more than just a numbers game?

PMID- 24293531
TI  - Coronary artery disease and age: beyond atherosclerosis.

PMID- 24293532
TI  - Treating hypertension by targeting orexin receptors: potential effects on the
      sleep-related blood pressure dipping profile.

PMID- 24293533
TI  - Reply from Aihua Li, Charles C. T. Hindmarch, Eugene E. Nattie and Julian F. R.
      Paton.

PMID- 24293534
TI  - An unusual cause of pneumonia: seen but not heard.
AB  - A 75-year-old man presented with a non-resolving pneumonia, malaise and weight
      loss. His medical history included a squamous cell carcinoma of the larynx and a
      non-small cell carcinoma of the lung. Chest CT showed right lower lobe collapse
      and consolidation. Bronchoscopy identified a foreign body in the right main
      bronchus and was subsequently removed with rigid bronchoscope. The removed
      foreign body was identified as a Blom-Singer speaking valve which had been
      aspirated 3 months previously. This is a rare complication of a speaking valve
      aspiration. This case illustrates the potential differential diagnoses of
      retained foreign bodies in the lung and that the symptoms can mimic neoplastic
      disease. Once removed, patients can have a dramatic improvement in quality of
      life and it is important to remember that a speaking valve may be aspirated, even
      if one present on the initial examination! 

PMID- 24293535
TI  - Cerebral arteriopathy associated with Arg179His ACTA2 mutation.
AB  - ACTA2 mutations have recently been shown to cause a multisystem smooth muscle
      dysfunction syndrome that may result in pediatric stroke. We report a case of
      ACTA2 mutation in a 3-year-old girl presenting with acute ischemic stroke and
      provide high resolution imaging of the cerebral arteries demonstrating novel
      findings of multiple tiny aneurysms (particularly in the posterior circulation),
      as well as the more characteristic imaging phenotype of straightened and narrowed
      proximal intracranial vessels, dilated cervical vessels and occlusion of the M1
      MCA segment without lenticulostriate collateral formation. This newly identified
      disease should be added to the differential diagnosis of pediatric stroke and
      cerebral vasculopathy. Neuroradiologists, interventionalists, surgeons and
      neurologists should become familiar with this rare disease and its clinical
      sequelae. 

PMID- 24293536
TI  - Pancreatic cancer presenting as a Sister Mary Joseph's nodule.
AB  - A 69-year-old man presented with a painful umbilical nodule of 1 month duration.
      On examination the nodule was blackish in colour with a serous discharging fluid
      and was 2*2 cm in size, tender and fixed to the skin. There were no scars or
      sinuses at the umbilicus and no palpable mass or organomegaly on systemic
      examination. The patient underwent wide local excision of the skin nodule and on
      histopathology was reported as metastatic adenocarcinoma of the skin. A CT of the
      abdomen was performed to look for the primary site, which showed a 5*4 cm lesion
      in the tail of the pancreas. A biopsy from the pancreatic lesion was taken which
      was reported as an adenocarcinoma. CA19-9 was more than 1000 U/mL. The patient
      was advised palliative chemotherapy with gemcitabine. He was unwilling to take
      any further treatment in view of the advanced nature of the disease. 

PMID- 24293537
TI  - Boerhaave's syndrome presenting as an upper gastrointestinal bleed.
AB  - A 64-year-old man without any significant medical history presented to accident
      and emergency department with haematemesis and melaena, quite similar to an upper
      gastrointestinal bleed. However, the unexplained left-sided neck pain with a
      history of overnight vomiting prompted further imaging. Air was visible in the
      soft tissues on a lateral X-ray of the neck, which led to a CT scan and this
      showed a proximal-mid oesophageal rupture. The patient was stabilised and
      transferred to a cardiothoracic unit for observation. An inpatient endoscopy did
      not detect a perforation and the patient was discharged 5 days later without any
      further complications. This case report highlights how a high oesophageal rupture
      can mimic an upper gastrointestinal bleed and also the need for further imaging
      when there is an incongruent history, so that appropriate care is provided to
      minimise mortality. 

PMID- 24293538
TI  - Stage 3 pyomyositis of the gluteus minimus; Staphylococcus aureus sepsis,
      autoanticoagulation, proximal femoral osteomyelitis and the role of surgical
      intervention.
AB  - Primary pyomyositis is a rare bacterial infection of the skeletal muscle.
      Traditionally a tropical disease, it is increasingly described in westernised
      urban populations. The aetiology is due to transient bacteraemia in the presence
      of risk factors such as traumatised muscle, or immunocompromise. The condition
      presents in one of three stages, representing progression of disease severity.
      Intravenous antibiotic therapy is often sufficient for this disease at its early
      stage, but surgical drainage is necessary for advanced presentations. We report a
      severe case of stage 3 pyomyositis of the gluteus minimus, which led to
      Staphylococcus aureus sepsis, deranged liver function, acute kidney injury,
      autoanticoagulation and proximal femoral osteomyelitis in a healthy 64-year-old
      Caucasian man. This illustrates the potential severity of the disease, the life
      threatening sequelae when diagnosis is delayed and the role of surgical drainage
      in averting the progression of systemic sepsis to end-organ dysfunction,
      disseminated intravascular coagulation and potentially death. 

PMID- 24293539
TI  - Recurrent cardiac tamponade in a young woman.
AB  - A young woman presented with recurrent pericardial effusion, she had previously
      been treated with antitubercular medications. She had clinical features of
      systemic sclerosis (SSc) which was subsequently confirmed on further workup. She
      was also found to be profoundly hypothyroid. Cardiac tamponade is uncommon in
      both SSc as well as hypothyroidism, unlike in our patient who was found to have
      both of these disorders. In her case, the pericardial involvement probably ante
      dated the other features of SSc. 

PMID- 24293540
TI  - Late relapse myoclonus in a case of Lance-Adams syndrome.
AB  - A 66-year-old man had a history of an anterior myocardial infarction followed by
      a successful cardiopulmonary resuscitation and a posthypoxic myoclonus, also
      known as Lance-Adams syndrome (LAS). Eight years ago, he was admitted to the
      emergency department with the same myoclonic jerks during an intercurrent
      respiratory infection. After treatment with clonazepam and resolution of the
      infection, the myoclonus promptly disappeared. This case report suggests that
      relapses of successfully treated LAS can occur in vulnerable patients, as it's a
      chronic form of myoclonus. 

PMID- 24293541
TI  - Compression neuropathy of the common peroneal nerve by the fabella.
AB  - The fabella is a normal anatomical variant and has been found in up to 30% of the
      general population. We present the case of a 67-year-old man with pain down the
      lateral aspect of the left lower limb of 18 months duration. A clinical
      examination revealed a palpable fabella and nerve conduction studies confirmed a
      common peroneal nerve neuropathy at its level. Dynamic ultrasound scan and MRI of
      the knee showed the fabella to be impinging on the common peroneal nerve.
      Operative excision of the fabella was performed with significant improvement at 3
      months and full recovery at 1 year. A literature review has shown that the last
      reported case of a compression neuropathy of the common peroneal nerve was in
      1976. Anatomical considerations need to be taken into account and operative
      treatment has been recommended due to the favourable outcome in this case. 

PMID- 24293542
TI  - Acute kidney injury as first presentation of lymphoma: the role of renal biopsy.
AB  - A 65-year-old man with an insidious history of being generally unwell with weight
      loss, a poor appetite and night sweats was transferred to a tertiary nephrology
      unit after being found to be in acute kidney injury (AKI). A renal biopsy was
      performed on the same day which revealed lymphomatous infiltration of the renal
      parenchyma. He required temporary haemodialysis as he was oliguric and was
      started on chemotherapy. His renal function improved to baseline 3 weeks after
      treatment. This case illustrates the uncommon presentation of direct lymphomatous
      infiltration as a cause of AKI and the integral role of renal biopsy in
      ascertaining the diagnosis. 

PMID- 24293543
TI  - Fracture of tibial tuberosity in an adult.
AB  - The fracture of tibial tuberosity is a rare lesion and still more unusual in
      adults. We describe a case in an adult who suffered a left knee injury due to a
      fall from height. No risk factors were identified. The lesion was treated with
      surgical reduction and internal fixation. The rehabilitation method was
      successful, resulting in excellent function and rage of motion of the knee. The
      aim of this study was to present an unusual case of direct trauma of the tibial
      tuberosity in an adult and the therapy performed. 

PMID- 24293545
TI  - DNAJB4 molecular chaperone distinguishes WT from mutant E-cadherin, determining
      their fate in vitro and in vivo.
AB  - E-cadherin (Ecad) is a well-known invasion suppressor and its loss of expression
      is common in invasive carcinomas. Germline Ecad mutations are the only known
      genetic cause of hereditary diffuse gastric cancer (HDGC), demonstrating the
      causative role of Ecad impairment in gastric cancer. HDGC-associated Ecad
      missense mutations can lead to folding defects and premature proteasome-dependent
      endoplasmic reticulum-associated degradation (ERAD), but the molecular
      determinants for this fate were unidentified. Using a Drosophila-based genetic
      screen, we found that Drosophila DnaJ-1 interacts with wild type (WT) and mutant
      human Ecad in vivo. DnaJ (Hsp40) homolog, subfamily B, member 4 (DNAJB4), the
      human homolog of DnaJ-1, influences Ecad localization and stability even in the
      absence of Ecad endogenous promoter, suggesting a post-transcriptional level of
      regulation. Increased expression of DNAJB4 leads to stabilization of WT Ecad in
      the plasma membrane, while it induces premature degradation of unfolded HDGC
      mutants in the proteasome. The interaction between DNAJB4 and Ecad is direct, and
      is increased in the context of the unfolded mutant E757K, especially when
      proteasome degradation is inhibited, suggesting that DNAJB4 is a molecular
      mediator of ERAD. Post-translational regulation of native Ecad by DNAJB4
      molecular chaperone is sufficient to influence cell adhesion in vitro. Using a
      chick embryo chorioallantoic membrane assay with gastric cancer derived cells, we
      demonstrate that DNAJB4 stimulates the anti-invasive function of WT Ecad in vivo.
      Additionally, the expression of DNAJB4 and Ecad is concomitantly decreased in
      human gastric carcinomas. Altogether, we demonstrate that DNAJB4 is a sensor of
      Ecad structural features that might contribute to gastric cancer progression. 

PMID- 24293544
TI  - Expression of alternative oxidase in Drosophila ameliorates diverse phenotypes
      due to cytochrome oxidase deficiency.
AB  - Mitochondrial dysfunction is a significant factor in human disease, ranging from
      systemic disorders of childhood to cardiomyopathy, ischaemia and
      neurodegeneration. Cytochrome oxidase, the terminal enzyme of the mitochondrial
      respiratory chain, is a frequent target. Lower eukaryotes possess alternative
      respiratory-chain enzymes that provide non-proton-translocating bypasses for
      respiratory complexes I (single-subunit reduced nicotinamide adenine dinucleotide
      dehydrogenases, e.g. Ndi1 from yeast) or III + IV [alternative oxidase (AOX)],
      under conditions of respiratory stress or overload. In previous studies, it was
      shown that transfer of yeast Ndi1 or Ciona intestinalis AOX to Drosophila was
      able to overcome the lethality produced by toxins or partial knockdown of complex
      I or IV. Here, we show that AOX can provide a complete or substantial rescue of a
      range of phenotypes induced by global or tissue-specific knockdown of different
      cIV subunits, including integral subunits required for catalysis, as well as
      peripheral subunits required for multimerization and assembly. AOX was also able
      to overcome the pupal lethality produced by muscle-specific knockdown of subunit
      CoVb, although the rescued flies were short lived and had a motility defect. cIV
      knockdown in neurons was not lethal during development but produced a rapidly
      progressing locomotor and seizure-sensitivity phenotype, which was substantially
      alleviated by AOX. Expression of Ndi1 exacerbated the neuronal phenotype produced
      by cIV knockdown. Ndi1 expressed in place of essential cI subunits produced a
      distinct residual phenotype of delayed development, bang sensitivity and male
      sterility. These findings confirm the potential utility of alternative
      respiratory chain enzymes as tools to combat mitochondrial disease, while
      indicating important limitations thereof. 

PMID- 24293549
TI  - Structural insights into the function of a thermostable copper-containing nitrite
      reductase.
AB  - Copper-containing nitrite reductase (CuNIR) catalyzes the reduction of nitrite
      (NO(-)2) to nitric oxide (NO) during denitrification. We determined the crystal
      structures of CuNIR from thermophilic gram-positive bacterium, Geobacillus
      thermodenitrificans (GtNIR) in chloride- and formate-bound forms of wild type at
      1.15 A resolution and the nitrite-bound form of the C135A mutant at 1.90 A
      resolution. The structure of C135A with nitrite displays a unique eta(1)-O
      coordination mode of nitrite at the catalytic copper site (T2Cu), which has never
      been observed at the T2Cu site in known wild-type CuNIRs, because the mobility of
      two residues essential to catalytic activity, Asp98 and His244, are sterically
      restricted in GtNIR by Phe109 on a characteristic loop structure that is found
      above Asp98 and by an unusually short CH-O hydrogen bond observed between His244
      and water, respectively. A detailed comparison of the WT structure with the
      nitrite-bound C135A structure implies the replacement of hydrogen-bond networks
      around His244 and predicts the flow path of protons consumed by nitrite
      reduction. On the basis of these observations, the reaction mechanism of GtNIR
      through the eta(1)-O coordination manner is proposed. 

PMID- 24293546
TI  - CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice.
AB  - Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is
      the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are
      major clinical features of CHARGE syndrome, affecting >75% of patients, it
      remains unclear whether CHD7 can directly regulate cardiogenic genes in embryos.
      Our complementary yeast two-hybrid and biochemical assays reveal that CHD7 is a
      novel interaction partner of canonical BMP signaling pathway nuclear mediators,
      SMAD1/5/8, in the embryonic heart. Moreover, CHD7 associates in a BMP-dependent
      manner with the enhancers of a critical cardiac transcription factor, Nkx2.5,
      that contain functional SMAD1-binding elements. Both the active epigenetic
      signature of Nkx2.5 regulatory elements and its proper expression in
      cardiomyocytes require CHD7. Finally, inactivation of Chd7 in mice impairs
      multiple BMP signaling-regulated cardiogenic processes. Our results thus support
      the model that CHD7 is recruited by SMAD1/5/8 to the enhancers of BMP-targeted
      cardiogenic genes to epigenetically regulate their expression. Impaired BMP
      activities in embryonic hearts may thus have a major contribution to CHDs in
      CHARGE syndrome. 

PMID- 24293552
TI  - Loneliness and social isolation: risk factors long overdue for surveillance.

PMID- 24293550
TI  - Addition of lysophosphatidic acid to mouse oocyte maturation media can enhance
      fertilization and developmental competence.
AB  - STUDY QUESTION: Does exposure to lysophosphatidic acid (LPA) during in vitro
      maturation (IVM) enhance the maturation and developmental competence of mouse
      oocytes? SUMMARY ANSWER: Supplementation of IVM medium with 30 MUM LPA enhanced
      the developmental competence of in vitro matured oocytes and so made them more
      comparable to in vivo matured control oocytes. WHAT IS KNOWN ALREADY: LPA is a
      small phospholipid that acts as an extracellular signaling molecule by binding to
      and activating at least five G protein-coupled receptors. LPA has various
      biological actions, with both developmental and physiological effects. STUDY
      DESIGN, SIZE, DURATION: During IVM, LPA at six different doses (0, 1, 10, 30, 50
      or 100 MUM) was added into the TCM-199 medium. After maturation, the
      developmental competence and other parameters of the oocytes were assessed.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Immature GV stage oocytes from 5- to 6
      week-old female BDF-1 mice were incubated for 17-18 h in IVM medium containing 0,
      1, 10 or 30 MUM LPA and then either fertilized in vitro with epididymal sperm, or
      assessed for spindle morphology, mitochondrial membrane potential (DeltaPsim) or
      the mRNA expression of a meiotic checkpoint gene (Mad2), a microtubule structure
      gene (Hook1), two maternally derived genes (Mater and Hsf1) and an apoptosis
      related gene (Caspase6). The fertilized embryos were grown in vitro to assess
      blastocyst-formation rates, differential cell counts and apoptosis. MAIN RESULTS
      AND THE ROLE OF CHANCE: Rates of maturation, fertilization and blastocyst
      formation and hatching were significantly higher in the 30 MUM LPA-supplemented
      group (94.3, 96.3, 79.1 and 51.3%, respectively) than in the unsupplemented
      control (0 MUM) group (80.5, 87.5, 61.3 and 37.8%, respectively) and more
      comparable to that of the in vivo matured oocytes (100, 96.5, 95.3 and 92.9%,
      respectively). LPA did not adversely affect mitochondrial activity, spindle
      integrity, blastocyst cell number, caspase positivity or Mad2 expression. Oocytes
      matured in 30 MUM LPA had reduced Caspase6 expression, but Hook1, Mater and Hsf1
      were up-regulated in all of the LPA-supplemented groups. LIMITATIONS, REASONS FOR
      CAUTION: Chromosomal aneuploidy in the resultant blastocysts and the production
      of normal pups were not assessed. Only mouse oocytes were assessed. WIDER
      IMPLICATIONS OF THE FINDINGS: Supplementation of IVM medium with 30 MUM LPA may
      enhance the developmental competence of mouse oocytes without affecting
      apoptosis, spindle normalcy or mitochondrial integrity. STUDY FUNDING/COMPETING
      INTEREST(S): This study was supported by a research grant (02-2012-021) from the
      Seoul National University Bundang Hospital. The authors declare that they have no
      competing interests.

PMID- 24293553
TI  - Permissive hypotension in bleeding trauma patients: helpful or not and when?
AB  - Severity of hemorrhage and rate of bleeding are fundamental factors in the
      outcomes of trauma. Intravenous administration of fluid is the basic treatment to
      maintain blood pressure until bleeding is controlled. The main guideline, used
      almost worldwide, Advanced Trauma Life Support, established by the American
      College of Surgeons in 1976, calls for aggressive administration of intravenous
      fluids, primarily crystalloid solutions. Several other guidelines, such as
      Prehospital Trauma Life Support, Trauma Evaluation and Management, and Advanced
      Trauma Operative Management, are applied according to a patient's current
      condition. However, the ideal strategy remains unclear. With permissive
      hypotension, also known as hypotensive resuscitation, fluid administration is
      less aggressive. The available models of permissive hypotension are based on
      hypotheses in hypovolemic physiology and restricted clinical trials in animals.
      Before these models can be used in patients, randomized, controlled clinical
      trials are necessary. 

PMID- 24293554
TI  - Brain death: assessment, controversy, and confounding factors.
AB  - When brain injury is refractory to aggressive management and is considered
      nonsurvivable, with loss of consciousness and brain stem reflexes, a brain death
      protocol may be initiated to determine death according to neurological criteria.
      Clinical evaluation typically entails 2 consecutive formal neurological
      examinations to document total loss of consciousness and absence of brain stem
      reflexes and then apnea testing to evaluate carbon dioxide unresponsiveness
      within the brain stem. Confounding factors such as use of therapeutic
      hypothermia, high-dose metabolic suppression, and movements associated with
      complex spinal reflexes, fasciculations, or cardiogenic ventilator autotriggering
      may delay initiation or completion of brain death protocols. Neurodiagnostic
      studies such as 4-vessel cerebral angiography can rapidly document absence of
      blood flow to the brain and decrease intervals between onset of terminal brain
      stem herniation and formal declaration of death by neurological criteria.
      Intracranial pathophysiology leading to brain death must be considered along with
      clinical assessment, patterns of vital signs, and relevant diagnostic studies. 

PMID- 24293555
TI  - Extubation with or without spontaneous breathing trial.
AB  - Purpose- To evaluate whether spontaneous breathing trials (SBTs) are necessary
      when extubating critical care patients. Methods- A prospective, randomized,
      double-blind study was performed in adult patients supported by mechanical
      ventilation for at least 48 hours in the general intensive care unit of a
      teaching hospital. Patients ready for weaning were randomly assigned to either
      the SBT group (extubation with an SBT) or the no-SBT group (extubation without an
      SBT). Patients in the SBT group who tolerated SBT underwent immediate extubation.
      Patients in the no-SBT group who met the weaning readiness criteria underwent
      extubation without an SBT. The primary outcome measure was a successful
      extubation or the ability to maintain spontaneous breathing for 48 hours after
      extubation. Results- A total of 139 adult patients were enrolled. No significant
      difference in the demographic, respiratory, and hemodynamic characteristics was
      indicated between the groups at the end of weaning readiness assessment.
      Successful extubation was achieved in 56 of 61 patients (91.8%) in the SBT group
      and 54 of 60 patients (90.0%) in the no-SBT group. In the SBT and no-SBT groups,
      5 (8.2%) and 6 (10.0%) patients, respectively, needed reintubation; 7 (11.5%) and
      9 (15.0%) patients, respectively, required noninvasive ventilation after
      extubation. In-hospital mortality did not differ significantly between the
      groups. Conclusion- Intensive care patients can be extubated successfully without
      an SBT. 

PMID- 24293556
TI  - Evidence-based prevention of pressure ulcers in the intensive care unit.
AB  - The development of stage III or IV pressure ulcers is currently considered a
      never event. Critical care patients are at high risk for development of pressure
      ulcers because of the increased use of devices, hemodynamic instability, and the
      use of vasoactive medications. This article addresses risk factors, risk scales
      such as the Norden, Braden, Waterlow, and Jackson-Cubbin scales used to determine
      the risk of pressure ulcers in critical care patients, and prevention of device
      related pressure ulcers in patients in the critical care unit. 

PMID- 24293557
TI  - The gift of certification.

PMID- 24293558
TI  - Avoiding infection when adding a urine meter.

PMID- 24293559
TI  - Surfactant therapy for bronchiolitis in critically ill infants.

PMID- 24293560
TI  - Elimination of catheter-associated urinary tract infections in an adult
      neurological intensive care unit.

PMID- 24293561
TI  - I am a critical care nurse.

PMID- 24293562
TI  - Spatially invariant coding of numerical information in functionally defined
      subregions of human parietal cortex.
AB  - Macaque electrophysiology has revealed neurons responsive to number in lateral
      (LIP) and ventral (VIP) intraparietal areas. Recently, fMRI pattern recognition
      revealed information discriminative of individual numbers in human parietal
      cortex but without precisely localizing the relevant sites or testing for
      subregions with different response profiles. Here, we defined the human
      functional equivalents of LIP (feLIP) and VIP (feVIP) using neurophysiologically
      motivated localizers. We applied multivariate pattern recognition to investigate
      whether both regions represent numerical information and whether number codes are
      position specific or invariant. In a delayed number comparison paradigm with
      laterally presented numerosities, parietal cortex discriminated between
      numerosities better than early visual cortex, and discrimination generalized
      across hemifields in parietal, but not early visual cortex. Activation patterns
      in the 2 parietal regions of interest did not differ in the coding of position
      specific or position-independent number information, but in the expression of a
      numerical distance effect which was more pronounced in feLIP. Thus, the
      representation of number in parietal cortex is at least partially position
      invariant. Both feLIP and feVIP contain information about individual numerosities
      in humans, but feLIP hosts a coarser representation of numerosity than feVIP,
      compatible with either broader tuning or a summation code. 

PMID- 24293563
TI  - The emergence of orthographic word representations in the brain: evaluating a
      neural shape-based framework using fMRI and the HMAX model. Addendum to
      retraction notice: 'The emergence of orthographic word representations in the
      brain: evaluating a neural shape-based framework using fMRI and the HMAX model'
      by Braet, W., Kubilius, J., Wagemans, J., & Op de Beeck, H. P.
      doi:10.1093/cercor/bhs355 (published online November 16, 2012, retracted May 17,
      2013).

PMID- 24293565
TI  - Subjective olfactory desensitization and recovery in humans.
AB  - Adaptation to smells is a well-known phenomenon and appears to be one of the
      major characteristics of olfaction. However, no standardized protocols for the
      psychophysical measurement of olfactory adaptation and recovery are available to
      date. Twenty normosmic participants were included. Hydrogen sulfide (H2S) and
      phenylethyl alcohol were used in different concentrations based on air dilution
      olfactometry. Volunteers were exposed to a constant flow of odorous air until
      perception disappeared completely. For testing recovery, the volunteers were
      exposed to a reference stimulus following complete self-desensitization with the
      same odor. The subjects were then again exposed to the same odorant after
      recovery periods of different lengths and instructed to rate stimulus intensity.
      The time to complete desensitization increased with increasing stimulus
      concentration for both odorants. Subjects desensitized more rapidly using H2S.
      Olfactory adaptation led to a reduction in stimulus intensity for the subsequent
      identical stimulation. Longer recovery periods resulted in increased intensity of
      the subsequent stimulus independent of the stimulus used. The results confirm
      current knowledge regarding the dynamics of olfactory adaptation and demonstrate
      differences in olfactory desensitization between the 2 odorants used. Olfactory
      recovery was independent of the odorant used, indicating that olfactory recovery
      after complete desensitization may be a uniform process. 

PMID- 24293564
TI  - Cognitive abilities on transitive inference using a novel touchscreen technology
      for mice.
AB  - Cognitive abilities are impaired in neurodevelopmental disorders, including
      autism spectrum disorder (ASD) and schizophrenia. Preclinical models with strong
      endophenotypes relevant to cognitive dysfunctions offer a valuable resource for
      therapeutic development. However, improved assays to test higher order cognition
      are needed. We employed touchscreen technology to design a complex transitive
      inference (TI) assay that requires cognitive flexibility and relational learning.
      C57BL/6J (B6) mice with good cognitive skills and BTBR T+tf/J (BTBR), a model of
      ASD with cognitive deficits, were evaluated in simple and complex touchscreen
      assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR
      displayed deficits on components of TI, when 4 stimuli pairs were interspersed,
      which required flexible integrated knowledge. BTBR displayed impairment on the A
      > E inference, analogous to the A > E deficit in ASD. B6 and BTBR mice both
      reached criterion on the B > D comparison, unlike the B > D impairment in
      schizophrenia. These results demonstrate that mice are capable of complex
      discriminations and higher order tasks using methods and equipment paralleling
      those used in humans. Our discovery that a mouse model of ASD displays a TI
      deficit similar to humans with ASD supports the use of the touchscreen technology
      for complex cognitive tasks in mouse models of neurodevelopmental disorders. 

PMID- 24293566
TI  - Associations of smoking and alcohol consumption with disease activity and
      functional status in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the associations of smoking and alcohol consumption
      with disease activity and functional status in rheumatoid arthritis (RA).
      METHODS: We conducted a prospective study consisting of 662 patients with RA who
      were followed up to 7 years from the Brigham and Women's Hospital Rheumatoid
      Arthritis Sequential Study. Smoking and alcohol consumption were assessed through
      yearly questionnaires. The disease activity and functional status were measured
      annually by the Disease Activity Score examined in 28 commonly affected joints
      using C-reactive protein (DAS28-CRP3) and the Modified Health Assessment
      Questionnaire (MHAQ). Linear mixed models were developed to assess the
      longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ
      after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE)
      by smoking and alcohol interactions were also evaluated in the analysis. RESULTS:
      The median followup time of the cohort was 4 years. Current smoking was not
      associated with DAS28-CRP3 in our study, but was associated with a higher MHAQ
      than nonsmokers with seropositive RA (p = 0.05). Alcohol consumption showed an
      approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1
      10.0 g/day. Compared to no alcohol use, alcohol consumption of 5.1-10.0 g/day was
      associated with a significant decrease of MHAQ (p = 0.02). When stratified by HLA
      SE, the effect of alcohol consumption appeared to be stronger in HLA-SE-positive
      RA than HLA-SE-negative RA. CONCLUSION: We found that current smoking was
      associated with a worse functional status, while moderate alcohol consumption was
      associated with a better functional status in RA. Replications of these findings
      in other prospective studies are needed.

PMID- 24293567
TI  - Interleukin 28B gene polymorphisms in hepatitis C virus-related cryoglobulinemic
      vasculitis.
AB  - OBJECTIVE: Single-nucleotide polymorphisms (SNP) in the interleukin 28B (IL-28B)
      gene region are strongly predictive of the response of infected patients to
      antiviral therapy for hepatitis C virus (HCV). We sought to determine the
      prevalence of SNP IL-28B rs12979860 C/C and non-C/C (C/T plus T/T) genotypes in
      HCV-related cryoglobulinemic vasculitis (CV), as compared with HCV-positive
      patients without CV. We also searched for their association with peculiar
      clinical manifestations of CV and potential influence on the complete response
      (virological, molecular, and immunological) to the therapy. METHODS: The study
      cohort comprised 159 and 172 HCV-infected patients with and without CV,
      respectively, prospectively followed starting from 1990. SNP rs12979860
      genotyping was performed by Taq-Man allelic discrimination. In 106 patients
      (66.6%) with CV, the profile of circulating B cell clonalities was determined as
      well. All patients with CV were treated with pegylated interferon-alpha/ribavirin
      based antiviral therapy. RESULTS: The T/T IL-28B genotype was more common in
      patients with CV than in those without (17% vs 8.1%, p = 0.02). In patients with
      CV, compared with non-C/C variants, the IL-28B C/C genotype was associated with a
      higher rate of complete response (52.6% vs 39.2%, p = 0.13), whereas a treatment
      response of 61.4% was demonstrated when solely virological response was
      considered (p = 0.008). A higher frequency of expanded B cell clonalities in the
      circulation (84.2% vs 55.9%; p = 0.005), kidney involvement (21% vs 2.9%; p =
      0.003), and B cell non-Hodgkin lymphoma (17.5% vs 6.8%; p = 0.048), were also
      observed. CONCLUSION: In HCV-positive patients with CV, the IL-28B C/C genotype
      is distinguished biologically by a higher frequency of restriction of B cell
      response and clinically by a higher risk of cryoglobulinemic nephropathy and B
      cell malignancies, while acting as an independent predictor of a sustained
      virological response to antiviral therapy. In addition, we found that IL-28B T/T
      variant was more prevalent in patients with CV than in those without.

PMID- 24293568
TI  - The OMERACT-RAMRIS rheumatoid arthritis magnetic resonance imaging joint space
      narrowing score: intrareader and interreader reliability and agreement with
      computed tomography and conventional radiography.
AB  - OBJECTIVE: To test the intrareader and interreader reliability of assessment of
      joint space narrowing (JSN) in rheumatoid arthritis (RA) wrist and
      metacarpophalangeal (MCP) joints on magnetic resonance imaging (MRI) and computed
      tomography (CT) using the newly proposed OMERACT-RAMRIS JSN scoring method, and
      to compare JSN assessment on MRI, CT, and radiography. METHODS: After calibration
      of readers, MRI and CT images of the wrist and second to fifth MCP joints from 14
      patients with RA and 1 healthy control were assessed twice for JSN by 3 readers,
      blinded to clinical and imaging data. Radiographs were scored by the Sharp/van
      der Heijde method. Intraclass correlation coefficients (ICC) and smallest
      detectable differences (SDD) were calculated, and the performance of various
      simplified scores was investigated. RESULTS: Both MRI and CT showed high
      intrareader (ICC >= 0.95) and interreader (ICC >= 0.94) reliability for total
      (wrist + MCP) assessment of JSN. Agreement was generally lower for MCP joints
      than for wrist joints, particularly for CT. Intrareader SDD for MCP/wrist/MCP +
      wrist were 1.2/6.1/6.4 JSN units for MRI, while 2.7/8.3/9.9 JSN units for CT. JSN
      on MRI and CT correlated moderately well with corresponding radiographic JSN
      scores (MCP 2-5: 0.49 and 0.56; wrist areas assessed by Sharp/van der Heijde:
      0.80 and 0.95), and high ICC between scores on MRI and CT were demonstrated (MCP:
      0.94; wrist: 0.92; MCP + wrist: 0.92). CONCLUSION: The OMERACT-RAMRIS MRI JSN
      scoring system showed high intrareader and interreader reliability, and high
      correlation with CT scores of JSN. The suggested JSN score may, after further
      validation in longitudinal studies, become a useful tool in RA clinical trials.

PMID- 24293569
TI  - Sleep problems in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate sleep problems, and the relationship between sleep and
      disease activity, in Belgian patients with established rheumatoid arthritis (RA).
      METHODS: This cross-sectional, observational, multicenter study assessed sleep
      quality using the Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index
      (PSQI), and daytime sleepiness using the Epworth Sleepiness Scale (ESS).
      Additional patient-reported outcomes included visual analog scales (VAS) for
      fatigue and pain, the Medical Outcomes Study Short Form-36 Health Survey, the
      Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Positive and
      Negative Affect Schedule. Multivariate regression and structural equation
      modeling identified factors associated with sleep quality, with the 28-joint
      Disease Activity Score [DAS28-C-reactive protein (CRP)] as a continuous or
      categorical variable. Analyses were performed on the total population and on
      patients stratified by disease activity status: remission/low (DAS28-CRP <= 3.2)
      or moderate to high (DAS28-CRP > 3.2). RESULTS: Among 305 patients, mean (SD) age
      was 57.00 (12.38) years and mean (SD) disease duration was 11.77 (9.94) years.
      Mean (SD) AIS, PSQI, and ESS scores were 6.8 (4.79), 7.8 (4.30), and 7.3 (4.67),
      respectively. Mean (SD) VAS fatigue, VAS pain, and HAQ-DI were 45.22 (26.29),
      39.04 (26.21), and 1.08 (0.75), respectively. There were significant positive
      relationships between DAS28-CRP and AIS/PSQI, but a significant negative
      relationship between DAS28-CRP and ESS. Several potentially confounding factors
      were identified. CONCLUSIONS: Poor control of RA is associated with a reduction
      in sleep quality and decreased daytime sleepiness, which is likely explained by
      pain-related alertness. Future prospective studies are needed to confirm
      potential relationships between sleep quality, sleepiness, and RA treatment.

PMID- 24293570
TI  - Iterative development and reliability of the OMERACT hand osteoarthritis MRI
      scoring system.
AB  - OBJECTIVE: To develop and test the interreader reliability of the OMERACT Hand
      Osteoarthritis Magnetic Resonance Scoring System (HOAMRIS) for assessment of
      structural and inflammatory hand OA features in the interphalangeal joints.
      METHODS: The HOAMRIS was developed through an iterative process. Selection of
      features and their scaling was agreed upon through consensus by members of the
      OMERACT Magnetic Resonance Imaging (MRI) Task Force, using the Oslo Hand
      Osteoarthritis (OA) MRI Score system as a template. Two reliability exercises
      were performed, in which 6 and 4 readers participated, respectively. After the
      first exercise, an atlas was developed and used in the second exercise to
      facilitate reading. In each exercise, readers independently scored 8 MRI scans
      from the Oslo Hand OA cohort (coronal/axial short-tau inversion recovery and
      coronal/axial/sagittal T1-weighted fat-suppressed pre-/post-Gadolinium images).
      Interreader reliability was assessed by intraclass correlation coefficients
      (ICC), percentage exact and close agreement (PEA/PCA). RESULTS: The preliminary
      OMERACT HOAMRIS included assessment of synovitis, erosive damage, cysts,
      osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML),
      of which all were scored on a 0-3 scale for normal, mild, moderate, and severe
      (increments of 0.5 for synovitis, erosive damage, and BML). In the first
      exercise, most features showed good to very good ICC values (0.64-0.94), except
      synovitis (0.34). In the second exercise using the atlas, the ICC values were >
      0.74 for all MRI features, and the PEA/PCA values were higher than in the first
      exercise. CONCLUSION: A preliminary HOAMRIS with good to very good interreader
      reliability was developed. Longitudinal studies are needed to assess its
      sensitivity to change.

PMID- 24293571
TI  - Update of strategies to translate evidence from cochrane musculoskeletal group
      systematic reviews for use by various audiences.
AB  - For rheumatology research to have a real influence on health and well-being,
      evidence must be tailored to inform the decisions of various audiences. The
      Cochrane Musculoskeletal Group (CMSG), one of 53 groups of the not-for-profit
      international Cochrane Collaboration, prepares, maintains, and disseminates
      systematic reviews of treatments for musculoskeletal diseases. While systematic
      reviews provided by the CMSG fill a major gap in meeting the need for high
      quality evidence syntheses, our work does not end at the completion of a review.
      The term "knowledge translation" (KT) refers to the activities involved in
      bringing research evidence to various audiences in a useful form so it can be
      used to support decision making and improve practices. Systematic reviews give
      careful consideration to research methods and analysis. Because the review is
      often long and detailed, the clinically relevant results may not be apparent or
      in the optimal form for use by patients and their healthcare practitioners. This
      paper describes 10 formats, many of them new, for ways that evidence from
      Cochrane Reviews can be translated with the intention of meeting the needs of
      various audiences, including patients and their families, practitioners, policy
      makers, the press, and members of the public (the "5 Ps"). Current and future
      knowledge tools include summary of findings tables, patient decision aids, plain
      language summaries, press releases, clinical scenarios in general medical
      journals, frequently asked questions (Cochrane Clinical Answers), podcasts,
      Twitter messages, Journal Club materials, and the use of storytelling and
      narratives to support continuing medical education. Future plans are outlined to
      explore ways of improving the influence and usefulness of systematic reviews by
      providing results in formats suitable to our varied audiences. 

PMID- 24293572
TI  - Fat infiltration on magnetic resonance imaging of the sacroiliac joints has
      limited diagnostic utility in nonradiographic axial spondyloarthritis.
AB  - OBJECTIVE: To explore whether morphological features of fat infiltration (FI) on
      sacroiliac joint (SIJ) magnetic resonance imaging (MRI) contribute to diagnostic
      utility in 2 inception cohorts of patients with nonradiographic axial
      spondyloarthritis (nr-axSpA). METHODS: Four blinded readers assessed SIJ MRI in 2
      cohorts (A/B) of 157 consecutive patients with back pain who were <= 50 years
      old, and in 20 healthy controls. Patients were classified according to clinical
      examination and pelvic radiography as having nr-axSpA (n = 51), ankylosing
      spondylitis (n = 34), or nonspecific back pain (n = 72). Readers recorded FI,
      bone marrow edema (BME), and erosion, predefined morphological features of FI
      (distinct border, homogeneity, subchondral location), and anatomical distribution
      of SIJ FI. The proportion of SIJ quadrants affected by FI and frequencies of
      various SIJ FI features were analyzed descriptively. We calculated
      positive/negative likelihood ratios (LR) to estimate the diagnostic utility of
      various features of FI, with and without associated BME, and erosion. RESULTS: Of
      the patients with nr-axSpA in cohorts A/B, 45.0%/48.4% had FI in >= 2 SIJ
      quadrants. Of those, 25.0%/22.6% and 20.0%/25.8% showed FI with distinct border
      or homogeneous pattern, respectively, and 50% to 100% of those patients displayed
      concomitant BME or erosion. FI per se in >= 2 SIJ quadrants had no diagnostic
      utility (LR+ 1.62/1.91). FI with distinct border (LR+ 8.29/2.13) or homogeneity
      (LR+ 6.24/3.78) demonstrated small to moderate diagnostic utility. CONCLUSION:
      SIJ FI per se was not of clinical utility in recognition of nr-axSpA. Distinct
      border or homogeneity of FI on SIJ MRI showed small to moderate diagnostic
      utility in nr-axSpA, but were strongly associated with concomitant BME or
      erosion, highlighting the contextual interpretation of SIJ MRI.

PMID- 24293573
TI  - Changes in body mass index in children with juvenile idiopathic arthritis treated
      with tumor necrosis factor inhibitors.
AB  - OBJECTIVE: To evaluate changes in body mass index (BMI) among cohorts of children
      with juvenile idiopathic arthritis (JIA) with and without tumor necrosis factor
      (TNF) inhibitor therapy. METHODS: We performed a retrospective chart review of
      children with JIA who newly initiated TNF inhibitor therapy and had at least 1
      year of subsequent followup (TNF cohort). We also included children with JIA and
      at least 1 year of followup without any TNF inhibitor therapy (comparator
      cohort). Children with systemic arthritis were excluded. Age and sex specific BMI
      z-scores and their corresponding categories (normal, overweight, obese) were
      determined. We compared changes from a baseline visit to the last followup visit
      using t-test for BMI z-scores and chi square and Kruskal-Wallis tests for BMI
      categories. RESULTS: The TNF cohort had 167 patients; the comparator cohort had
      37. The median study followup was 2.8 and 2.2 years, respectively. The cohorts
      had similar age, sex, race, weight, and height distributions. The TNF cohort had
      a statistically significant increase in BMI z-score from baseline (+0.15; p =
      0.02) that was not significantly different from the increase (+0.09) observed in
      the comparator cohort (p = 0.5). There was no significant change in the
      proportions of overweight and obese children in the TNF cohort compared to
      baseline (p = 0.6) or compared to the change in the comparator cohort (p = 0.2).
      CONCLUSION: Over more than 2 years of followup, we did not observe a significant
      increase in BMI among children with JIA receiving TNF inhibitor compared to those
      not receiving it.

PMID- 24293574
TI  - Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate
      dihydrate crystal deposition disease.
AB  - OBJECTIVE: Accumulation of excess extracellular inorganic pyrophosphate leads to
      calcium pyrophosphate dihydrate (CPPD) crystal formation in articular cartilage.
      CPPD crystal formation occurs near morphologically abnormal chondrocytes
      resembling hypertrophic chondrocytes. The ANK protein was recently implicated as
      an important factor in the transport of intracellular inorganic pyrophosphate
      across the cell membrane. We characterized ANK in joint tissues from patients
      with and without CPPD deposition and correlated the presence of ANK with markers
      of chondrocyte hypertrophy. METHODS: Articular tissues were obtained from 24
      patients with CPPD crystal deposition disease, 11 patients with osteoarthritis
      (OA) without crystals, and 6 controls. We determined the number of ANK-positive
      cells in joint tissues using immunohistochemistry and in situ hybridization, and
      correlated ANK positivity with markers of chondrocyte hypertrophy including
      Runx2, type X collagen, osteopontin (OPN), and osteocalcin (OCN). RESULTS: ANK
      was detected in synoviocytes, chondrocytes, osteoblasts, and osteocytes. ANK was
      seen extracellularly only in the matrix of cartilage and meniscus. The number of
      ANK-positive cells was significantly higher in CPPD than in OA or normal joint
      tissues. The amount and intensity of ANK immunoreactivity reached maximum levels
      in the large chondrocytes around crystal deposits. ANK was similarly distributed
      to and significantly correlated with Runx2, type X collagen, OPN, and OCN.
      CONCLUSION: ANK levels were higher in articular tissues from patients with CPPD
      deposition. ANK was concentrated around crystal deposits and correlated with
      markers of chondrocyte hypertrophy. These findings support a role for ANK in CPPD
      crystal formation in cartilage.

PMID- 24293575
TI  - One-year followup study on clinical findings and changes in magnetic resonance
      imaging-based disease activity scores in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate whether clinical disease activity findings during 1-year
      followup of patients with juvenile idiopathic arthritis (JIA) is associated with
      changes of magnetic resonance imaging (MRI)-based disease activity scores.
      METHODS: Patients with JIA who had active knee involvement were studied using an
      open-bore MRI. After followup of a median of 1.3 years, patients were re
      evaluated and classified as improved or unimproved according to the American
      College of Rheumatology Pediatric-50 (ACR-Ped50) criteria. Baseline and followup
      MRI features were scored by 2 readers using the Juvenile Arthritis MRI Scoring
      (JAMRIS) system, comprising validated scores for synovial hypertrophy, bone
      marrow changes, cartilage lesions, and bone erosions. RESULTS: Data of 40
      patients were analyzed (62.5% female, mean age 12.2 yrs). After followup, 27
      patients (67.5%) were classified as clinically improved, whereas 13 patients
      (32.5%) showed no clinical improvement. The clinically improved patients showed a
      significant reduction in synovial hypertrophy scores during followup (p < 0.001),
      with substantial effects (standardized response mean -0.70). No such changes were
      observed for any of the other MRI features. Significant differences were detected
      regarding a change in synovial hypertrophy scores comparing clinically improved
      and unimproved patients (p = 0.004), without statistically significant
      differences for changes in scores for bone marrow changes (p = 0.079), cartilage
      lesions (p = 0.165), and bone erosions (p = 0.078). CONCLUSION: This is one of
      the first studies to provide evidence for MRI-based improvement upon followup in
      JIA patients with knee involvement. There is a strong association with clinical
      improvement according to the ACR-Ped50 criteria and changes in MRI-based synovial
      hypertrophy scores, supporting the role of MRI as a responsive outcome measure to
      evaluate disease activity with antiinflammatory treatment strategies.

PMID- 24293576
TI  - Effect of biologic treatments on growth in children with juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: Growth retardation is a frequent complication of severe juvenile
      idiopathic arthritis (JIA). Biologic treatments may improve growth velocity by
      controlling systemic inflammation and reducing corticosteroids. Our goals were to
      compare growth velocity before and after the onset of biologic therapy and to
      determine whether the JIA subtype, the use of steroids, the requirement of one or
      several biologic agents, or the disease activity influenced growth velocity.
      METHODS: We retrospectively analyzed the growth of children with JIA who never
      received growth hormone treatment, who started biologic treatment before puberty,
      and who were followed for at least 6 months afterward. RESULTS: We included 100
      children (33 boys). Median patient age was 7.1 years (range: 1.6-15.7) at the
      onset of biologic treatment and 11.0 years (range: 2.3-19.5) at the latest
      followup. Forty-six patients had received corticosteroid and 34 had received more
      than 1 biologic agent. Patient median height expressed as SD score (SDS) was 0.31
      (range: -2.47 to 5.46) at disease onset, -0.24 (-3.63 to 2.90) at biologic
      therapy onset (p < 0.0001), and -0.15 (-4.95 to 3.52) at the latest followup (p =
      0.171 compared to biologic treatment onset). Patients who required several
      biologics and systemic patients had a significantly lower growth velocity after
      the onset of biologic treatment. At the latest followup, 18% of our study group
      had low growth velocities and 19% were below -2SD or shorter than genetically
      programmed. CONCLUSION: In a subset of patients, particularly systemic JIA
      patients and patients who required more than 1 biologic, biologic therapy may be
      insufficient to restore normal growth velocity.

PMID- 24293577
TI  - Clinical features of patients with morphea and the pansclerotic subtype: a cross
      sectional study from the morphea in adults and children cohort.
AB  - OBJECTIVE: Pansclerotic morphea is a poorly described form of morphea with little
      information on prevalence, demographics, and clinical features. Classification
      criteria for this subtype varies and the distinction from other forms of morphea,
      such as extensive generalized morphea and pansclerotic morphea, is not always
      clear. The purpose of our study was to clarify classification criteria for
      pansclerotic morphea by identifying its prevalence in the morphea in adults and
      children (MAC) cohort and describing its demographic and clinical features as
      compared with generalized morphea. METHODS: Patients who met predefined criteria
      for generalized and pansclerotic morphea were identified using a modified Laxer
      and Zulian classification system. Baseline demographic and clinical features of
      the patients were compiled and then analyzed for traits characteristic of
      pansclerotic morphea versus those of generalized morphea. One hundred and
      thirteen patients met the criteria for inclusion: pansclerotic (n = 13) and
      generalized morphea type (n = 100). RESULTS: Patients with pansclerotic morphea
      were more frequently male (46.2% vs 6%; p < 0.0001); had a shorter time to
      diagnosis (mean difference of 10.4 mos; 95% CI: 0.8-19.9 mos; p = 0.0332); higher
      rates of functional impairment (61.5% vs 16%; p = 0.0046); higher rates of deep
      involvement (61.5% vs 17%; p = 0.004); and higher average Rodnan Skin Score (mean
      difference of 10.8 points; 95% CI: 5-16.6; p = 0.0017), Localized Scleroderma
      Skin Damage Index (mean difference 28.3; 95% CI: 9-47.6; p = 0.009), and
      Physician Global Assessment of Disease Damage scores (mean difference 25.1; 95%
      CI: 0.3-50; p = 0.048). CONCLUSION: Our results suggest demographic and clinical
      features are sufficient to define the pansclerotic subtype as they represent a
      distinct clinical phenotype with a more rapidly progressive and severe course
      commonly accompanied by disability. Presence of features of the pansclerotic
      phenotype should alert practitioners to the possibility of significant morbidity
      and the need for early aggressive treatment.

PMID- 24293578
TI  - Effect of low-dose oral prednisolone on symptoms and systemic inflammation in
      older adults with moderate to severe knee osteoarthritis: a randomized placebo
      controlled trial.
AB  - OBJECTIVE: To investigate the efficacy of 6 weeks of daily low-dose oral
      prednisolone in improving pain, mobility, and systemic low-grade inflammation in
      the short term and whether the effect would be sustained at 12 weeks in older
      adults with moderate to severe knee osteoarthritis (OA). METHODS: A total of 125
      patients with primary knee OA were randomized 1:1; 63 received 7.5 mg/day of
      prednisolone and 62 received placebo for 6 weeks. Outcome measures included pain
      reduction and improvement in function scores and systemic inflammation markers.
      Pain was assessed using the visual analog pain scale (0-100 mm). Secondary
      outcome measures included the Western Ontario and McMaster Universities
      Osteoarthritis Index scores, patient global assessment (PGA) of the severity of
      knee OA, and 6-min walk distance (6MWD). Serum levels of interleukin 1 (IL-1), IL
      6, tumor necrosis factor (TNF)-alpha, and high-sensitivity C-reactive protein
      (hsCRP) were measured. RESULTS: There was a clinically relevant reduction in the
      intervention group compared to the placebo group for knee pain, physical
      function, PGA, and 6MWD at 6 weeks. The mean difference between treatment arms
      (95% CI) was 10.9 (4.8-18.0), p < 0.001; 9.5 (3.7-15.4), p < 0.05; 15.7 (5.3
      26.1), p < 0.001; and 86.9 (29.8-144.1), p < 0.05, respectively. Further, there
      was a clinically relevant reduction in the serum levels of IL-1, IL-6, TNF-alpha,
      and hsCRP at 6 weeks in the intervention group when compared to the placebo
      group. These differences remained significant at 12 weeks. The Outcome Measures
      in Rheumatology Clinical Trials-Osteoarthritis Research Society International
      responder rate was 65% in the intervention group and 34% in the placebo group (p
      < 0.05). CONCLUSION: Low-dose oral prednisolone had both a short-term and a
      longer sustained effect resulting in less knee pain, better physical function,
      and attenuation of systemic inflammation in older patients with knee OA
      (ClinicalTrials.gov identifier NCT01619163).

PMID- 24293579
TI  - Update on the OMERACT magnetic resonance imaging task force: research and future
      directions.
AB  - Magnetic resonance imaging (MRI) provides an important biomarker across a range
      of rheumatological diseases. At the Outcome Measures in Rheumatology (OMERACT) 11
      meeting, the MRI task force continued its work of developing and improving the
      use of MRI outcomes for use in clinical trials. The breadth of pathology in the
      Rheumatoid Arthritis MRI Score has been strengthened with further work on the
      development of a joint space narrowing score, and a series of exercises presented
      at OMERACT 11 demonstrated good reliability and construct validity for this
      assessment. Understanding the importance of residual inflammation after RA
      treatment remains a major focus of the group's work. Analyses were presented on
      defining the level of synovitis (using MRI scores of a single hand) that would
      predict absence of erosion progression. The development of the OMERACT Hand
      Osteoarthritis MRI score has continued with substantial work presented on its
      iterative development, including pathology definition, scaling, and subsequent
      reliability of the score. Optimizing the role of MRI as a robust biomarker and
      surrogate outcome remains a priority for this group. 

PMID- 24293580
TI  - Variability in recommendations for total knee arthroplasty among rheumatologists
      and orthopedic surgeons.
AB  - OBJECTIVE: The most rapidly growing population of patients undergoing total knee
      arthroplasty (TKA) is under the age of 65. The objective of our study was to gain
      insight into the factors influencing physicians' recommendations for persons in
      this age group with moderate osteoarthritis (OA). METHODS: Rheumatologists and
      orthopedic surgeons attending national meetings were asked to complete a survey
      including a standardized scenario of a 62-year-old person with knee OA who has
      moderate knee pain limiting strenuous activity despite medical management. We
      used an experimental 2 * 2 * 2 design to examine the effects of sex, employment
      status, and severity of radiographic OA on physicians' recommendations. Each
      physician was asked to rate a single scenario. RESULTS: The percentage of
      physicians recommending TKA varied from 30% to 55% for scenarios describing a
      patient with mild radiographic OA, and from 39% to 71% for scenarios describing a
      patient with moderate radiographic OA. Surgeons were less likely to recommend TKA
      for women compared to men of the same age, employment status, symptom severity,
      and functional status, and radiographs. Rheumatologists practicing in academic
      settings were more likely to recommend TKA compared to those practicing in
      nonacademic settings, and American surgeons were more likely to recommend TKA
      compared to their European counterparts. CONCLUSION: Orthopedic surgeons and
      rheumatologists vary significantly in their recommendations for patients with
      moderate knee pain and functional limitations. Both patient and physician
      characteristics influence physicians' recommendations, and rheumatologists and
      orthopedic surgeons display different patterns of decision making.

PMID- 24293581
TI  - Updated method guidelines for cochrane musculoskeletal group systematic reviews
      and metaanalyses.
AB  - The Cochrane Musculoskeletal Group (CMSG), one of 53 groups of the not-for
      profit, international Cochrane Collaboration, prepares, maintains, and
      disseminates systematic reviews of treatments for musculoskeletal diseases. It is
      important that authors conducting CMSG reviews and the readers of our reviews be
      aware of and use updated, state-of-the-art systematic review methodology. One
      hundred sixty reviews have been published. Previous method guidelines for
      systematic reviews of interventions in the musculoskeletal field published in
      2006 have been substantially updated to incorporate methodological advances that
      are mandatory or highly desirable in Cochrane reviews and knowledge translation
      advances. The methodological advances include new guidance on searching, new risk
      of-bias assessment, grading the quality of the evidence, the new Summary of
      Findings table, and comparative effectiveness using network metaanalysis. Method
      guidelines specific to musculoskeletal disorders are provided by CMSG editors for
      various aspects of undertaking a systematic review. These method guidelines will
      help improve the quality of reporting and ensure high standards of conduct as
      well as consistency across CMSG reviews. 

PMID- 24293582
TI  - Does clinically important change in function after knee replacement guarantee
      good absolute function? The multicenter osteoarthritis study.
AB  - OBJECTIVE: Poor functional outcomes post-knee replacement are common, but
      estimates of its prevalence vary, likely in part because of differences in
      methods used to assess function. The agreement between improvement in function
      and absolute good levels of function after knee replacement has not been
      evaluated. We evaluated the attainment of improvement in function and absolute
      good function after total knee replacement (TKR) and the agreement between these
      measures. METHODS: Using data from The Multicenter Osteoarthritis (MOST) Study,
      we determined the prevalence of achieving a minimal clinically important
      improvement (MCII, >= 14.2/68 point improvement) and Patient Acceptable Symptom
      State (PASS, <= 22/68 post-TKR score) on the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) Physical Function subscale at least 6
      months after knee replacement. We also assessed the frequency of co-occurrence of
      the 2 outcomes, and the prevalence according to pre-knee replacement functional
      status. RESULTS: We included 228 subjects who had a knee replacement during
      followup (mean age 65 yrs, mean body mass index 33.4, 73% female). Seventy-one
      percent attained the PASS for function after knee replacement, while only 44%
      attained the MCII. Of the subjects who met the MCII, 93% also attained the PASS;
      however, of subjects who did not meet the MCII, 54% still achieved a PASS.
      Baseline functional status was associated with attainment of each MCII and PASS.
      CONCLUSION: There was only partial overlap between attainment of a good level of
      function and actually improving by an acceptable amount. Subjects were more
      likely to attain an acceptable level of function than to achieve a clinically
      important amount of improvement post-knee replacement.

PMID- 24293583
TI  - Clinical, functional, and radiographic implications of time to treatment response
      in patients with early rheumatoid arthritis: a posthoc analysis of the PREMIER
      study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) treatment recommendations suggest target
      attainment within the first 3 months of therapy, yet delayed clinical responses
      can occur. This analysis assessed the longterm clinical, functional, and
      radiographic outcomes associated with delayed responses to methotrexate (MTX)
      monotherapy or to the combination of adalimumab (ADA) + MTX. METHODS: In this
      posthoc analysis, patients with early RA who received MTX monotherapy or ADA +
      MTX in the PREMIER study were categorized based on clinical responses at 3 and 6
      months [American College of Rheumatology response, 28-joint Disease Activity
      Score (DAS28)-C-reactive protein (CRP) improvement and targets]. "Month 3"
      responders met the clinical measure at both months 3 and 6, and "Month 6"
      responders met the clinical measure only at Month 6. The odds of achieving
      longterm outcomes [remission (DAS28-CRP < 2.6), normal function (Health
      Assessment Questionnaire-Disability Index < 0.5), or rapid radiographic
      progression (Delta modified total Sharp score > 3 U/yr)] were modeled using
      logistic regression, including treatment, response, and interaction. RESULTS: A
      delayed or low-level response was associated with poorer longterm outcomes.
      Generally, MTX Month 6 responders demonstrated worse clinical, functional, and
      radiographic outcomes than Month 3 MTX and Month 3 or 6 ADA + MTX responders.
      Although similar longterm benefit was observed for ADA + MTX responders, delayed
      (Month 6) responders exhibited downward trends in clinical, functional, and
      radiographic outcomes that were comparable with those experienced by Month 3 MTX
      responders. CONCLUSION: Response speed and magnitude predict longterm outcomes in
      patients with early RA treated with MTX or ADA + MTX. MTX-treated patients
      failing to demonstrate a Month 3 clinical response have less-favorable outcomes
      than other groups, while outcomes in ADA + MTX Month 3 and Month 6 responders
      tended to be comparable.

PMID- 24293584
TI  - Prevalence, correlates and outcomes of gastric antral vascular ectasia in
      systemic sclerosis: a EUSTAR case-control study.
AB  - OBJECTIVE: To estimate the prevalence, determine the subgroups at risk, and the
      outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular
      ectasia (GAVE). METHODS: We queried the European League Against Rheumatism
      Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients
      with SSc-GAVE. Each case was matched for cutaneous subset and disease duration
      with 2 controls with SSc recruited from the same center, evaluated at the time
      the index case made the diagnosis of GAVE. SSc characteristics were recorded at
      the time GAVE occurred and the last observation was collected to define the
      outcomes. RESULTS: Forty-nine patients with SSc and GAVE were included (24 with
      diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of
      GAVE was estimated at about 1% of patients with SSc. By multivariate analysis,
      patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value
      (OR 12.8; 95% CI 1.9-82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95%
      CI 0.1-0.6). GAVE was also associated with the presence of anti-RNA-polymerase
      III antibodies (OR 4.6; 95% CI 1.2-21.1). SSc-GAVE was associated with anemia
      (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were
      performed in 45% of patients with GAVE. After a median followup of 30 months
      (range 1-113 months), survival was similar in patients with SSc-GAVE compared to
      controls, but a higher number of scleroderma renal crisis cases occurred (12% vs
      2%; p = 0.01). CONCLUSION: GAVE is rare and associated with a vascular phenotype,
      including anti-RNA-polymerase III antibodies, and a high risk of renal crisis.
      Anemia, usually requiring blood transfusions, is a common complication.

PMID- 24293585
TI  - Joint Registries: a Ptolemaic model of data interpretation?

PMID- 24293586
TI  - Enhanced recovery in total hip replacement: a clinical review.
AB  - The outcome after total hip replacement has improved with the development of
      surgical techniques, better pain management and the introduction of enhanced
      recovery pathways. These pathways require a multidisciplinary team to manage pre
      operative education, multimodal pain control and accelerated rehabilitation. The
      current economic climate and restricted budgets favour brief hospitalisation
      while minimising costs. This has put considerable pressure on hospitals to
      combine excellent results, early functional recovery and shorter admissions. In
      this review we present an evidence-based summary of some common interventions and
      methods, including pre-operative patient education, pre-emptive analgesia, local
      infiltration analgesia, pre-operative nutrition, the use of pulsed
      electromagnetic fields, peri-operative rehabilitation, wound dressings, different
      surgical techniques, minimally invasive surgery and fast-track joint replacement
      units.

PMID- 24293587
TI  - Controversies relating to the management of acromioclavicular joint dislocations.
AB  - The aim of this review is to address controversies in the management of
      dislocations of the acromioclavicular joint. Current evidence suggests that
      operative rather than non-operative treatment of Rockwood grade III dislocations
      results in better cosmetic and radiological results, similar functional outcomes
      and longer time off work. Early surgery results in better functional and
      radiological outcomes with a reduced risk of infection and loss of reduction
      compared with delayed surgery. Surgical options include acromioclavicular
      fixation, coracoclavicular fixation and coracoclavicular ligament reconstruction.
      Although non-controlled studies report promising results for arthroscopic
      coracoclavicular fixation, there are no comparative studies with open techniques
      to draw conclusions about the best surgical approach. Non-rigid coracoclavicular
      fixation with tendon graft or synthetic materials, or rigid acromioclavicular
      fixation with a hook plate, is preferable to fixation with coracoclavicular
      screws owing to significant risks of loosening and breakage. The evidence,
      although limited, also suggests that anatomical ligament reconstruction with
      autograft or certain synthetic grafts may have better outcomes than non
      anatomical transfer of the coracoacromial ligament. It has been suggested that
      this is due to better restoration horizontal and vertical stability of the joint.
      Despite the large number of recently published studies, there remains a lack of
      high-quality evidence, making it difficult to draw firm conclusions regarding
      these controversial issues.

PMID- 24293588
TI  - Ceramic-on-ceramic bearings in young patients: outcomes and activity levels at
      minimum ten-year follow-up.
AB  - We report the clinical and radiological outcomes of a series of contemporary
      cementless ceramic-on-ceramic total hip replacements (THRs) at ten years in
      patients aged <= 55 years of age. Pre- and post-operative activity levels are
      described. A total of 120 consecutive ceramic cementless THRs were performed at a
      single centre in 110 patients from 1997 to 1999. The mean age of the patients at
      operation was 45 years (20 to 55). At ten years, four patients had died and six
      were lost to follow-up, comprising ten hips. The mean post-operative Harris hip
      score was 94.7 (55 to 100). Radiological analysis was undertaken in 90 available
      THRs of the surviving 106 hips at final review: all had evidence of stable bony
      ingrowth, with no cases of osteolysis. Wear was undetectable. There were four
      revisions. The survival for both components with revision for any cause as an
      endpoint was 96.5% (95% confidence interval 94.5 to 98.7). The mean modified
      University of California, Los Angeles activity level rose from a mean of 6.4 (4
      to 10) pre-operatively to 9.0 (6 to 10) at the ten-year post-operative period.
      Alumina ceramic-on-ceramic bearings in cementless primary THR in this series have
      resulted in good clinical and radiological outcomes with undetectable rates of
      wear and excellent function in the demanding younger patient group at ten years.

PMID- 24293589
TI  - Clinical results, radiological findings and survival of a proximally
      hydroxyapatite-coated hip ABG II stem at a minimum of ten years' follow-up:
      results of a consecutive multicentre study of 1148 hips in 1053 patients.
AB  - We report a multicentre prospective consecutive study assessing the long-term
      outcome of the proximally hydroxyapatite (HA)-coated ABG II monobloc femoral
      component in a series of 1148 hips in 1053 patients with a mean age at surgery of
      64.77 years (22 to 80) at a mean follow-up of 10.84 years (10 to 15.25). At
      latest follow-up, the mean total Harris hip score was 94.7 points (sd; 6.87; 49
      to 100), and the mean Merle d'Aubigne-Postel score was 17.6 points (sd 1.12; 7 to
      18). The mean total Engh radiological score score was 21.54 (sd 5.77; 3.5 to 27),
      with 95.81% of 'confirmed ingrowth', according to Engh's classification. With
      aseptic loosening or pain as endpoints, three AGB II stems (0.26%) failed, giving
      a 99.7% survival rate (se 0.002; 95% confidence interval (CI) 0.994 to 1) at 14
      years' follow-up. The survival of patients <= 50 years of age (99.0% (se 0.011;
      95% CI 0.969 to 1)) did not differ significantly from those of patients aged > 50
      years (99.8% (se 0.002; 95% CI 0.994 to 1)). This study confirmed the excellent
      long-term results currently achieved with the ABG II proximally HA-coated
      monobloc stem. Cite this article: Bone Joint J 2013;95-B:1610-16.

PMID- 24293590
TI  - Clinical and radiological outcome of the cemented Contemporary acetabular
      component in patients < 50 years of age.
AB  - Despite the worldwide usage of the cemented Contemporary acetabular component
      (Stryker), no published data are available regarding its use in patients aged <
      50 years. We undertook a mid- to long-term follow-up study, including all
      consecutive patients aged < 50 years who underwent a primary total hip
      replacement using the Contemporary acetabular component with the Exeter cemented
      stem between January 1999 and January 2006. There were 152 hips in 126 patients,
      61 men and 65 women, mean age at surgery 37.6 years (16 to 49 yrs). One patient
      was lost to follow-up. Mean clinical follow-up of all implants was 7.6 years (0.9
      to 12.0). All clinical questionnaire scores, including Harris hip score, Oxford
      hip score and several visual analogue scales, were found to have improved. The
      eight year survivorship of all acetabular components for the endpoints revision
      for any reason or revision for aseptic loosening was 94.4% (95% confidence
      interval (CI) 89.2 to 97.2) and 96.4% (95% CI 91.6 to 98.5), respectively.
      Radiological follow-up was complete for 146 implants. The eight year survival for
      the endpoint radiological loosening was 93.1% (95% CI 86.2 to 96.6). Three
      surviving implants were considered radiologically loose but were asymptomatic.
      The presence of acetabular osteolysis (n = 17, 11.8%) and radiolucent lines (n =
      20, 13.9%) in the 144 surviving cups indicates a need for continued observation
      in the second decade of follow-up in order to observe their influence on long
      term survival. The clinical and radiological data resulting in a ten-year
      survival rate > 90% in young patients support the use of the Contemporary
      acetabular component in this specific patient group.

PMID- 24293591
TI  - Asymptomatic pseudotumours after metal-on-metal hip resurfacing show little
      change within one year.
AB  - The aim of this study was to establish the natural course of unrevised
      asymptomatic pseudotumours after metal-on-metal (MoM) hip resurfacing during a
      six- to 12-month follow-up period. We used repeated metal artefact reduction
      sequence (MARS)-magnetic resonance imaging (MRI), serum metal ion analysis and
      clinical examination to study 14 unrevised hips (mean patient age 52.7 years, 46
      to 68, 5 female, 7 male) with a pseudotumour and 23 hips (mean patient age 52.8
      years, 38 to 69, 7 female, 16 male) without a pseudotumour. The mean post
      operative time to the first MARS-MRI scan was 4.3 years (2.2 to 8.3), and mean
      time between the first and second MARS-MRI scan was eight months (6 to 12). At
      the second MRI scan, the grade of severity of the pseudotumour had not changed in
      35 hips. One new pseudotumour (Anderson C2 score, moderate) was observed, and one
      pseudotumour was downgraded from C2 (moderate) to C1 (mild). In general, the
      characteristics of the pseudotumours hardly changed. Repeated MARS-MRI scans
      within one year in patients with asymptomatic pseudotumours after MoM hip
      resurfacing showed little or no variation. In 23 patients without pseudotumour,
      one new asymptomatic pseudotumour was detected. This is the first longitudinal
      study on the natural history of pseudotumours using MARS-MRI scans in hip
      resurfacing, and mirrors recent results for 28 mm diameter MoM total hip
      replacement.

PMID- 24293592
TI  - Total knee replacement in patients with concomitant back pain results in a worse
      functional outcome and a lower rate of satisfaction.
AB  - This study assessed the effect of concomitant back pain on the Oxford knee score
      (OKS), Short-Form (SF)-12 and patient satisfaction after total knee replacement
      (TKR). It involved a prospectively compiled database of demographics and outcome
      scores for 2392 patients undergoing primary TKR, of whom 829 patients (35%)
      reported back pain. Compared with those patients without back pain, those with
      back pain were more likely to be female (odds ratio (OR) 1.5 (95% confidence
      interval (CI) 1.3 to 1.8)), have a greater level of comorbidity, a worse pre
      operative OKS (2.3 points (95% CI 1.7 to 3.0)) and worse SF-12 physical (2.0
      points (95% CI 1.4 to 2.6)) and mental (3.3 points (95% CI 2.3 to 4.3))
      components. One year post-operatively, those with back pain had significantly
      worse outcome scores than those without with a mean difference in the OKS of 5
      points (95% CI 3.8 to 5.4), in the SF-12 physical component of 6 points (95% CI
      5.4 to 7.1) and in the mental component of 4 points (95% CI 3.1 to 4.9). Patients
      with back pain were less likely to be satisfied (OR 0.62, 95% CI 0.5 to 0.78).
      After adjusting for confounding variables, concomitant back pain was an
      independent predictor of a worse post-operative OKS, and of dissatisfaction.
      Clinicians should be aware that patients suffering concomitant back pain pre
      operatively are at an increased risk of being dissatisfied post-operatively.

PMID- 24293593
TI  - Metal metaphyseal sleeves in revision total knee replacement.
AB  - Bone loss in the proximal tibia and distal femur is frequently encountered in
      revision knee replacement surgery. The various options for dealing with this
      depend on the extent of any bone loss. We present our results with the use of
      cementless metaphyseal metal sleeves in 103 patients (104 knees) with a mean
      follow-up of 43 months (30 to 65). At final follow-up, sleeves in 102 knees had
      good osseointegration. Two tibial sleeves were revised for loosening, possibly
      due to infection. The average pre-operative Oxford Knee Score was 23 (11 to 36)
      and this improved to 32 (15 to 46) post-operatively. These early results
      encourage us to continue with the technique and monitor the outcomes in the long
      term.

PMID- 24293594
TI  - Popliteal artery injury during knee replacement: a population-based nationwide
      study.
AB  - Popliteal artery injury (PAI) is a feared complication during knee replacement.
      Our aim was to investigate those injuries that occurred in association with knee
      replacement in terms of the type of injury, treatment and outcomes. From our
      national vascular registry (Swedvasc) and the Swedish Patient Insurance databases
      a total of 32 cases were identified. Prospective data from the registries was
      supplemented with case-records, including long-term follow-up. We estimated the
      incidence during 1998 to 2010 to be 0.017%. In our series of 32 patients with PAI
      occurring between 1987 and 2011, 25 (78%) were due to penetrating trauma and
      seven were caused by blunt trauma. The patients presented in three ways: bleeding
      (14), ischaemia (7) and false aneurysm formation (11), and five occurred during
      revision surgery. A total of 12 injuries were detected intra-operatively, eight
      within 24 hours (3 to 24) and 12 at more than 24 hours post-operatively (2 to 90
      days). Treatment comprised open surgery in 28 patients. Patency of the vascular
      repair at 30 days was 97% (31 of 32, one amputation). At the time of follow-up
      (median 546 days, mean 677 days (24 to 1251)), 25 patients had residual symptoms.
      Of seven patients with a complete recovery, six had had an early diagnosis of the
      PAI during the procedure, and were treated by a vascular surgeon in the same
      hospital. PAI is a rare adverse event during knee replacement surgery. The
      outcome following such events is often adversely affected by diagnostic and
      therapeutic delay. Bleeding and false aneurysm were the most common clinical
      presentations.

PMID- 24293595
TI  - Treatment of osteochondral defects of the talus with a metal resurfacing inlay
      implant after failed previous surgery: a prospective study.
AB  - We have evaluated the clinical effectiveness of a metal resurfacing inlay implant
      for osteochondral defects of the medial talar dome after failed previous surgical
      treatment. We prospectively studied 20 consecutive patients with a mean age of 38
      years (20 to 60), for a mean of three years (2 to 5) post-surgery. There was
      statistically significant reduction of pain in each of four situations (i.e.,
      rest, walking, stair climbing and running; p <= 0.01). The median American
      Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from 62
      (interquartile range (IQR) 46 to 72) pre-operatively to 87 (IQR 75 to 95) at
      final follow-up (p < 0.001). The Foot and Ankle Outcome Score improved on all
      subscales (p <= 0.03). The mean Short-Form 36 physical component scale improved
      from 36 (23 to 50) pre-operatively to 45 (29 to 55) at final follow-up (p =
      0.001); the mental component scale did not change significantly. On radiographs,
      progressive degenerative changes of the opposing tibial plafond were observed in
      two patients. One patient required additional surgery for the osteochondral
      defect. This study shows that a metal implant is a promising treatment for
      osteochondral defects of the medial talar dome after failed previous surgery.

PMID- 24293596
TI  - Long-term follow-up of mobile-bearing total ankle replacement in patients with
      inflammatory joint disease.
AB  - Little is known about the long-term outcome of mobile-bearing total ankle
      replacement (TAR) in the treatment of end-stage arthritis of the ankle, and in
      particular for patients with inflammatory joint disease. The aim of this study
      was to assess the minimum ten-year outcome of TAR in this group of patients. We
      prospectively followed 76 patients (93 TARs) who underwent surgery between 1988
      and 1999. No patients were lost to follow-up. At latest follow-up at a mean of
      14.8 years (10.7 to 22.8), 30 patients (39 TARs) had died and the original TAR
      remained in situ in 28 patients (31 TARs). The cumulative incidence of failure at
      15 years was 20% (95% confidence interval (CI) 11 to 28). The mean American
      Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score of the surviving
      patients at latest follow-up was 80.4 (95% CI 72 to 88). In total, 21 patients
      (23 TARs) underwent subsequent surgery: three implant exchanges, three bearing
      exchanges and 17 arthrodeses. Neither design of TAR described in this study, the
      LCS and the Buechel-Pappas, remains currently available. However, based both on
      this study and on other reports, we believe that TAR using current mobile-bearing
      designs for patients with end-stage arthritis of the ankle due to inflammatory
      joint disease remains justified.

PMID- 24293597
TI  - Screw fixation of medial malleolar fractures: a cadaveric biomechanical study
      challenging the current AO philosophy.
AB  - The AO Foundation advocates the use of partially threaded lag screws in the
      fixation of fractures of the medial malleolus. However, their threads often
      bypass the radiodense physeal scar of the distal tibia, possibly failing to
      obtain more secure purchase and better compression of the fracture. We therefore
      hypothesised that the partially threaded screws commonly used to fix a medial
      malleolar fracture often provide suboptimal compression as a result of bypassing
      the physeal scar, and proposed that better compression of the fracture may be
      achieved with shorter partially threaded screws or fully threaded screws whose
      threads engage the physeal scar. We analysed compression at the fracture site in
      human cadaver medial malleoli treated with either 30 mm or 45 mm long partially
      threaded screws or 45 mm fully threaded screws. The median compression at the
      fracture site achieved with 30 mm partially threaded screws (0.95 kg/cm(2)
      (interquartile range (IQR) 0.8 to 1.2) and 45 mm fully threaded screws (1.0
      kg/cm(2) (IQR 0.7 to 2.8)) was significantly higher than that achieved with 45 mm
      partially threaded screws (0.6 kg/cm(2) (IQR 0.2 to 0.9)) (p = 0.04 and p <
      0.001, respectively). The fully threaded screws and the 30mm partially threaded
      screws were seen to engage the physeal scar under an image intensifier in each
      case. The results support the use of 30 mm partially threaded or 45 mm fully
      threaded screws that engage the physeal scar rather than longer partially
      threaded screws that do not. A 45 mm fully threaded screw may in practice offer
      additional benefit over 30 mm partially threaded screws in increasing the thread
      count in the denser paraphyseal region.

PMID- 24293598
TI  - Bone transport with an external fixator and a locking plate for segmental tibial
      defects.
AB  - Although gradual bone transport may permit the restoration of large-diameter
      bones, complications are common owing to the long duration of external fixation.
      In order to reduce such complications, a new technique of bone transport
      involving the use of an external fixator and a locking plate was devised for
      segmental tibial bone defects. A total of ten patients (nine men, one woman) with
      a mean age at operation of 40.4 years (16 to 64) underwent distraction
      osteogenesis with a locking plate to treat previously infected post-traumatic
      segmental tibial defects. The locking plate was fixed percutaneously to bridge
      proximal and distal segments, and was followed by external fixation. After
      docking, percutaneous screws were fixed at the transported segment through plate
      holes. At the same time, bone grafting was performed at the docking site with the
      external fixator removed. The mean defect size was 5.9 cm (3.8 to 9.3) and mean
      external fixation index was 13.4 days/cm (11.8 to 19.5). In all cases, primary
      union of the docking site and distraction callus was achieved, with an excellent
      bony result. There was no recurrence of deep infection or osteomyelitis, and with
      the exception of one patient with a pre-existing peroneal nerve injury, all
      achieved an excellent or good functional result. With short external fixation
      times and low complication rates, bone transport with a locking plate could be
      recommended for patients with segmental tibial defects.

PMID- 24293599
TI  - Distraction osteogenesis in the treatment of long bone defects of the lower
      limbs: effectiveness, complications and clinical results; a systematic review and
      meta-analysis.
AB  - We carried out a systematic review of the literature to evaluate the evidence
      regarding the clinical results of the Ilizarov method in the treatment of long
      bone defects of the lower limbs. Only 37 reports (three non-randomised
      comparative studies, one prospective study and 33 case-series) met our inclusion
      criteria. Although several studies were unsatisfactory in terms of statistical
      heterogeneity, our analysis appears to show that the Ilizarov method of
      distraction osteogenesis significantly reduced the risk of deep infection in
      infected osseous lesions (risk ratio 0.14 (95% confidence interval (CI) 0.10 to
      0.20), p < 0.001). However, there was a rate of re-fracture of 5% (95% CI 3 to
      7), with a rate of neurovascular complications of 2.2% (95% CI 0.3 to 4) and an
      amputation rate of 2.9% (95% CI 1.4 to 4.4).The data was generally not
      statistically heterogeneous. Where tibial defects were > 8 cm, the risk of re
      fracture increased (odds ratio 3.7 (95% CI 1.1 to 12.5), p = 0.036). The
      technique is demanding for patients, illustrated by the voluntary amputation rate
      of 1.6% (95% CI 0 to 3.1), which underlines the need for careful patient
      selection.

PMID- 24293600
TI  - Two-stage revision for the treatment of the infected total elbow arthroplasty.
AB  - We report our experience of staged revision surgery for the treatment of infected
      total elbow arthroplasty (TEA). Between 1998 and 2010 a consecutive series of 33
      patients (34 TEAs) underwent a first-stage procedure with the intention to
      proceed to second-stage procedure when the infection had been controlled. A
      single first-stage procedure with removal of the components and cement was
      undertaken for 29 TEAs (85%), followed by the insertion of antibiotic-impregnated
      cement beads, and five (15%) required two or more first-stage procedures. The
      most common organism isolated was coagulase-negative Staphylococcus in 21 TEAs
      (62%). A second-stage procedure was performed for 26 TEAs (76%); seven patients
      (seven TEAs, 21%) had a functional resection arthroplasty with antibiotic beads
      in situ and had no further surgery, one had a persistent discharge preventing
      further surgery. There were three recurrent infections (11.5%) in those patients
      who underwent a second-stage procedure. The infection presented at a mean of
      eight months (5 to 10) post-operatively. The mean Mayo Elbow Performance Score
      (MEPS) in those who underwent a second stage revision without recurrent infection
      was 81.1 (65 to 95). Staged revision surgery is successful in the treatment of
      patients with an infected TEA and is associated with a low rate of recurrent
      infection. However, when infection does occur, this study would suggest that it
      becomes apparent within ten months of the second stage procedure.

PMID- 24293601
TI  - Simple debridement has little useful value on the clinical course of recalcitrant
      ulnar wrist pain.
AB  - The purpose of this study was to evaluate treatment results following
      arthroscopic triangular fibrocartilage complex (TFCC) debridement for
      recalcitrant ulnar wrist pain. According to the treatment algorithm, 66 patients
      (36 men and 30 women with a mean age of 38.1 years (15 to 67)) with recalcitrant
      ulnar wrist pain were allocated to undergo ulnar shortening osteotomy (USO; n =
      24), arthroscopic TFCC repair (n = 15), arthroscopic TFCC debridement (n = 14) or
      prolonged conservative treatment (n = 13). The mean follow-up was 36.0 months (15
      to 54). Significant differences in Hand20 score at 18 months were evident between
      the USO group and TFCC debridement group (p = 0.003), and between the TFCC repair
      group and TFCC debridement group (p = 0.029). Within-group comparisons showed
      that Hand20 score at five months or later and pain score at two months or later
      were significantly decreased in the USO/TFCC repair groups. In contrast, scores
      in the TFCC debridement/conservative groups did not decrease significantly. Grip
      strength at 18 months was significantly improved in the USO/TFCC repair groups,
      but not in the TFCC debridement/conservative groups. TFCC debridement shows
      little benefit on the clinical course of recalcitrant ulnar wrist pain even after
      excluding patients with ulnocarpal abutment or TFCC detachment from the fovea
      from the indications for arthroscopic TFCC debridement.

PMID- 24293602
TI  - Management and incidence of tibial tubercle fractures in bicondylar fractures of
      the tibial plateau.
AB  - Bicondylar tibial plateau fractures result from high-energy injuries. Fractures
      of the tibial plateau can involve the tibial tubercle, which represents a
      disruption to the extensor mechanism and logically must be stabilised. The
      purpose of this study was to identify the incidence of an independent tibial
      tubercle fracture in bicondylar tibial plateau fractures, and to report
      management strategies and potential complications. We retrospectively reviewed a
      prospectively collected orthopaedic trauma database for the period January 2003
      to December 2008, and identified 392 bicondylar fractures of the tibial plateau,
      in which 85 tibial tubercle fractures (21.6%) were identified in 84 patients.
      There were 60 men and 24 women in our study group, with a mean age of 45.4 years
      (18 to 71). In 84 fractures open reduction and internal fixation was undertaken,
      either with screws alone (23 patients) or with a plate and screws (61 patients).
      The remaining patient was treated non-operatively. In all, 52 fractures were
      available for clinical and radiological assessment at a mean follow-up of 58.5
      weeks (24 to 94). All fractures of the tibial tubercle united, but 24 of 54
      fractures (46%) required a secondary procedure for their tibial plateau fracture.
      Four patients reported pain arising from prominent tubercle plates and screws,
      which in one patient required removal. Tibial tubercle fractures occurred in over
      one-fifth of the bicondylar tibial plateau fractures in our series. Fixation is
      necessary and can be reliably performed with screws alone or with a screw and
      plate, which restores the extensor mechanism and facilitates early knee flexion.

PMID- 24293603
TI  - Does human immunodeficiency virus status affect early wound healing in open
      surgically stabilised tibial fractures?: A prospective study.
AB  - We compared early post-operative rates of wound infection in HIV-positive and 
      negative patients presenting with open tibial fractures managed with surgical
      fixation. The wounds of 84 patients (85 fractures), 28 of whom were HIV positive
      and 56 were HIV negative, were assessed for signs of infection using the ASEPIS
      wound score. There were 19 women and 65 men with a mean age of 34.8 years. A
      total of 57 fractures (17 HIV-positive, 40 HIV-negative) treated with external
      fixation were also assessed using the Checkett score for pin-site infection. The
      remaining 28 fractures were treated with internal fixation. No significant
      difference in early post-operative wound infection between the two groups of
      patients was found (10.7% (n = 3) vs 19.6% (n = 11); relative risk (RR) 0.55 (95%
      confidence interval (CI) 0.17 to 1.8); p = 0.32). There was also no significant
      difference in pin-site infection rates (17.6% (n = 3) vs 12.5% (n = 5); RR 1.62
      (95% CI 0.44 to 6.07); p = 0.47). The study does not support the hypothesis that
      HIV significantly increases the rate of early wound or pin-site infection in open
      tibial fractures. We would therefore suggest that a patient's HIV status should
      not alter the management of open tibial fractures in patients who have a CD4
      count > 350 cells/MUl.

PMID- 24293604
TI  - Avascular necrosis after chemotherapy for haematological malignancy in childhood.
AB  - Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for
      haematological malignancy in childhood. In order to describe its incidence and
      main risk factors and to evaluate the current treatment options, we reviewed 105
      children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or
      acute myeloid leukaemia, or a non-Hodgkin's lymphoma. Overall, eight children
      (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys
      and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18
      involved sites, 12 of which were in the femoral head. All these children were
      aged > nine years (p < 0.001). All had received steroid treatment with a mean
      cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of
      3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed
      between genders and no thrombophilic disorders were identified. Their initial
      treatment included 11 core decompressions and two bipolar hip replacements.
      Later, two salvage osteotomies were done and three patients (four hips)
      eventually needed a total joint replacement. We conclude that AVN mostly affects
      the weight-bearing epiphyses. Its risk increases with age and higher steroid
      doses. These high-risk patients may benefit from early screening for AVN.

PMID- 24293605
TI  - The treatment of stable paediatric forearm fractures using a cast that may be
      removed at home: comparison with traditional management in a randomised
      controlled trial.
AB  - We investigated whether, in the management of stable paediatric fractures of the
      forearm, flexible casts that can be removed at home are as clinically effective,
      cost-effective and acceptable to both patient and parent as management using a
      cast conventionally removed in hospital. A single-centre randomised controlled
      trial was performed on 317 children with a mean age of 9.3 years (2 to 16). No
      significant differences were seen in the change in Childhood Health Assessment
      Questionnaire index score (p = 0.10) or EuroQol 5-Dimensions domain scores
      between the two groups one week after removal of the cast or the absolute scores
      at six months. There was a significantly lower overall median treatment cost in
      the group whose casts were removed at home (L150.88 (sem 1.90) vs L251.62 (sem
      2.68); p < 0.001). No difference was seen in satisfaction between the two groups
      (p = 0.48).

PMID- 24293606
TI  - The Ponseti method in the treatment of children with idiopathic clubfoot
      presenting between five and ten years of age.
AB  - Our goal was to evaluate the use of Ponseti's method, with minor adaptations, in
      the treatment of idiopathic clubfeet presenting in children between five and ten
      years of age. A retrospective review was performed in 36 children (55 feet) with
      a mean age of 7.4 years (5 to 10), supplemented by digital images and video
      recordings of gait. There were 19 males and 17 females. The mean follow-up was
      31.5 months (24 to 40). The mean number of casts was 9.5 (6 to 11), and all
      children required surgery, including a percutaneous tenotomy or open tendo
      Achillis lengthening (49%), posterior release (34.5%), posterior medial soft
      tissue release (14.5%), or soft-tissue release combined with an osteotomy (2%).
      The mean dorsiflexion of the ankle was 9 degrees  (0 degrees  to 15 degrees ).
      Forefoot alignment was neutral in 28 feet (51%) or adducted (< 10 degrees ) in 20
      feet (36%), > 10 degrees  in seven feet (13%). Hindfoot alignment was neutral or
      mild valgus in 26 feet (47%), mild varus (< 10 degrees ) in 19 feet (35%), and
      varus (> 10 degrees ) in ten feet (18%). Heel-toe gait was present in 38 feet
      (86%), and 12 (28%) exhibited weight-bearing on the lateral border (out of a
      total of 44 feet with gait videos available for analysis). Overt relapse was
      identified in nine feet (16%, six children). The parents of 27 children (75%)
      were completely satisfied. A plantigrade foot was achieved in 46 feet (84%)
      without an extensive soft-tissue release or bony procedure, although under
      correction was common, and longer-term follow-up will be required to assess the
      outcome.

PMID- 24293609
TI  - Chromogenic in situ hybridisation (CISH) is a powerful method to detect ALK
      positive non-small cell lung carcinomas.
AB  - AIM: We assessed the potential of a chromogenic in situ hybridisation (CISH)
      assay in comparison with quantitative reverse transcription (RT)-PCR (qPCR) to
      detect anaplastic lymphoma kinase (ALK) break apart-positive lung carcinomas.
      METHODS: Dual-colour CISH using a break apart probe for the ALK gene on 2p23 was
      performed with 181 formalin-fixed, paraffin-embedded tissue and agar block
      sections from 175 cases of non-small cell lung carcinomas (NSCLC). Stained slides
      were analysed with a standard bright-field microscope at 1000* magnification by
      counting signals from 60 non-overlapping nuclei from three different tumour
      areas. Samples with >=15% of positive nuclei were judged as ALK break apart
      positive. All samples were simultaneously analysed by qPCR for EML4-ALK to
      validate CISH results, and positive samples were subject to Sanger sequencing.
      RESULTS: CISH was successful with 173 of 181 hybridised samples (96%), and seven
      ALK break apart-positive cases were detected. CISH signals were specific and
      distinct for both colours. All positive cases were confirmed by qPCR and Sanger
      sequencing, and concordance between CISH and qPCR was 100%. Nearly all samples
      (9/10) which failed by qPCR were accessible to CISH analysis. CONCLUSIONS: CISH
      is a very reliable, convenient and inexpensive method to detect ALK-positive
      NSCLC. CISH success rate is comparably high as with qPCR, and it detects all ALK
      break apart events in a single assay. It is of special value when RNA quality is
      poor, or when small biopsies with a very limited amount of tumour cells have to
      be analysed.

PMID- 24293610
TI  - Alteration of energy metabolism in the pathogenesis of bile duct lesions in
      primary biliary cirrhosis.
AB  - AIM: Primary biliary cirrhosis (PBC) is characterised by antimitochondrial
      antibody against the pyruvate dehydrogenase complex (PDC) and chronic non
      suppurative destructive cholangitis (CNSDC). Pyruvate oxidation to acetyl-CoA by
      PDC is a key step in the glycolytic system. Oestrogen-related receptor-alpha
      (ERRalpha) is functionally activated by inducible coactivators such as peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and Bcl-3.
      Moreover, the PGC-1alpha-ERRalpha axis interrupts glycolytic metabolism through
      the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which
      functionally inhibits PDC-E1alpha and stimulates fatty acid oxidation. In this
      study, we investigated the PGC-1alpha-ERRalpha axis to clarify PDC dysfunction in
      CNSDC of PBC. METHODS: The expression of PGC-1alpha, Bcl-3, ERRalpha, PDK4 and
      PDC-E1alpha was examined by immunohistochemistry in liver sections from patients
      with PBC and controls. The expression of these molecules, the activity of
      mitochondrial dehydrogenase and PDC, and their alterations by starvation, a
      treatment used to induce PGC-1alpha expression, were examined in cultured human
      biliary epithelial cells (BECs). RESULTS: The nuclear expression of PGC-1alpha,
      Bcl-3 and ERRalpha was exclusively observed in CNSDC of PBC. Moreover, the
      expression of PDK4 and PDC-E1alpha was enhanced in CNSDC of PBC. In cultured
      BECs, the amplification of Bcl-3 and PDK4 mRNAs by reverse-transcription-PCR and
      mitochondrial dehydrogenase activity were markedly increased but PDC activity was
      decreased according to the upregulation of PGC-1alpha. CONCLUSIONS: In CNSDC of
      PBC, the activation of the ERRalpha-PGC-1alpha axis was exclusively observed,
      suggesting the interference of PDC-related glycolytic function and the induction
      of the fatty acid degradation system. The switching of the cellular energy system
      is possibly associated with the pathogenesis of CNSDC in PBC.

PMID- 24293611
TI  - Expression of thymoproteasome subunit beta5t in type AB thymoma.
AB  - Type AB thymoma is a thymic epithelial tumour composed of lymphocyte-poor type A
      and lymphocyte-rich type B components. Although it is categorised as a single
      entity in the classification of WHO, it shows a broad range of morphology. To
      investigate whether the functional characteristic of neoplastic cells in type AB
      thymoma relates to morphological diversity, we performed immunohistochemical
      analysis using anti-beta5t antibody in 20 cases of type AB thymoma. beta5t is a
      recently discovered proteasomal beta subunit expressed exclusively in cortical
      thymic epithelial cells and tumour epithelial cells of thymomas with cortical
      differentiation. Consistent with our previous observation, beta5t was
      predominantly expressed in the type B component. When the type B component was
      divided into three groups morphologically, beta5t was expressed more frequently
      in cases with round to polygonal than spindle to oval tumour cells. Furthermore,
      the ratio of terminal deoxynucleotidyl transferase (TdT)-positive lymphocytes was
      increased in components with higher expression of beta5t. These results indicate
      that the histological diversity of type AB thymoma correlates with expression of
      a functional marker beta5t and abundance of TdT-positive lymphocytes. 

PMID- 24293612
TI  - Substantial roles of hexokinase and fructokinase in the effects of sugars on
      plant physiology and development.
AB  - The basic requirements for plant growth are light, CO2, water, and minerals.
      However, the absorption and utilization of each of these requires investment on
      the part of the plant. The primary products of plants are sugars, and the hexose
      sugars glucose and fructose are the raw material for most of the metabolic
      pathways and organic matter in plants. To be metabolized, hexose sugars must
      first be phosphorylated. Only two families of enzymes capable of catalysing the
      essential irreversible phosphorylation of glucose and fructose have been
      identified in plants, hexokinases (HXKs) and fructokinases (FRKs). These hexose
      phosphorylating enzymes appear to coordinate sugar production with the abilities
      to absorb light, CO2, water, and minerals. This review describes the long- and
      short-term effects mediated by HXK and FRK in various tissues, as well as the
      role of these enzymes in the coordination of sugar production with the absorption
      of light, CO2, water, and minerals.

PMID- 24293613
TI  - Molecular mechanisms involved in plant adaptation to low K(+) availability.
AB  - Potassium is a major inorganic constituent of the living cell and the most
      abundant cation in the cytosol. It plays a role in various functions at the cell
      level, such as electrical neutralization of anionic charges, protein synthesis,
      long- and short-term control of membrane polarization, and regulation of the
      osmotic potential. Through the latter function, K(+) is involved at the whole
      plant level in osmotically driven functions such as cell movements, regulation of
      stomatal aperture, or phloem transport. Thus, plant growth and development
      require that large amounts of K(+) are taken up from the soil and translocated to
      the various organs. In most ecosystems, however, soil K(+) availability is low
      and fluctuating, so plants have developed strategies to take up K(+) more
      efficiently and preserve vital functions and growth when K(+) availability is
      becoming limited. These strategies include increased capacity for high-affinity
      K(+) uptake from the soil, K(+) redistribution between the cytosolic and vacuolar
      pools, ensuring cytosolic homeostasis, and modification of root system
      development and architecture. Our knowledge about the mechanisms and signalling
      cascades involved in these different adaptive responses has been rapidly growing
      during the last decade, revealing a highly complex network of interacting
      processes. This review is focused on the different physiological responses
      induced by K(+) deprivation, their underlying molecular events, and the present
      knowledge and hypotheses regarding the mechanisms responsible for K(+) sensing
      and signalling.

PMID- 24293615
TI  - ANCA-associated vasculitis: a prothrombotic state even in remission?

PMID- 24293614
TI  - The American Quarter Horse: population structure and relationship to the
      thoroughbred.
AB  - A breed known for its versatility, the American Quarter Horse (QH), is
      increasingly bred for performance in specific disciplines. The impact of
      selective breeding on the diversity and structure of the QH breed was evaluated
      using pedigree analysis and genome-wide SNP data from horses representing 6
      performance groups (halter, western pleasure, reining, working cow, cutting, and
      racing). Genotype data (36 037 single nucleotide polymorphisms [SNPs]) from 36
      Thoroughbreds were also evaluated with those from the 132 performing QHs to
      evaluate the Thoroughbred's influence on QH diversity. Results showed significant
      population structure among all QH performance groups excepting the comparison
      between the cutting and working cow horses; divergence was greatest between the
      cutting and racing QHs, the latter of which had a large contribution of
      Thoroughbred ancestry. Significant coancestry and the potential for inbreeding
      exist within performance groups, especially when considering the elite
      performers. Relatedness within performance groups is increasing with popular
      sires contributing disproportionate levels of variation to each discipline.
      Expected heterozygosity, inbreeding, F ST, cluster, and haplotype analyses
      suggest these QHs can be broadly classified into 3 categories: stock, racing, and
      pleasure/halter. Although the QH breed as a whole contains substantial genetic
      diversity, current breeding practices have resulted in this variation being
      sequestered into subpopulations. 

PMID- 24293616
TI  - Tuberculosis screening before and during treatment with tumor necrosis factor
      antagonists: something old, something new.

PMID- 24293617
TI  - Interleukin 6 targeting in refractory Takayasu arteritis: serial noninvasive
      imaging is mandatory to monitor efficacy.

PMID- 24293618
TI  - Cardiovascular risk in rheumatoid arthritis (RA): does it matter if RA is
      diagnosed in early or late age?

PMID- 24293619
TI  - The kidney in familial Mediterranean fever.

PMID- 24293620
TI  - Isolated inflammatory arthritis of the atlantooccipital joint confused with
      migraine.

PMID- 24293621
TI  - Clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography in Takayasu arteritis -- a report of 3 demonstrative cases.

PMID- 24293622
TI  - Expression of podoplanin in minor salivary glands increases in primary Sjogren
      syndrome.

PMID- 24293623
TI  - Rituximab for primary angiitis of the central nervous system: report of 2
      patients from the French COVAC cohort and review of the literature.

PMID- 24293627
TI  - CD8+ T cell-independent tumor regression induced by Fc-OX40L and therapeutic
      vaccination in a mouse model of glioma.
AB  - Despite the growing number of preclinical and clinical trials focused on
      immunotherapy for the treatment of malignant gliomas, the prognosis for this
      disease remains grim. Although some promising advances have been made, the immune
      response stimulated as a result of immunotherapeutic protocols has been
      inefficient at complete tumor elimination, primarily due to our lack of
      understanding of the necessary effector functions of the immune system. We
      previously demonstrated that a tumor lysate vaccine/Fc-OX40L therapy is capable
      of inducing enhanced survival and tumor elimination in the GL261 mouse glioma
      model. The following experiments were performed to determine the mechanism(s) of
      action of this therapy that elicits a potent antitumor immune response. The
      evidence subsequently outlined indicates a CD8(+) T cell-independent and CD4(+) T
      cell-, NK cell-, and B cell-dependent means of prolonged survival. CD8(+) T cell
      independent tumor clearance is surprising considering the current focus of many
      cancer immunotherapy protocols. These results provide evidence for CD8(+) T cell
      independent means of antitumor response and should lead to additional examination
      of the potential manipulation of this mechanism for future treatment strategies. 

PMID- 24293628
TI  - MyD88 signaling regulates both host defense and immunopathogenesis during
      pneumocystis infection.
AB  - The immune response protects against Pneumocystis infection but is also a key
      component of Pneumocystis pneumonia (PcP)-related immunopathogenesis. Signaling
      through myeloid differentiation factor 88 (MyD88) is critical for activation of
      immune pathways downstream of TLRs and IL-1R. To determine whether MyD88
      regulates normal host defense against Pneumocystis, nonimmunosuppressed wild-type
      (WT) and MyD88-deficient mice were infected. MyD88(-/-) mice had higher early
      Pneumocystis burdens than did WT mice but mounted an effective adaptive immune
      response and cleared Pneumocystis similarly to WT. However, MyD88(-/-) mice
      displayed a more intense and prolonged pulmonary immune response than did WT
      mice. To determine the role of MyD88 in the development of PcP-related
      immunopathogenesis, WT and MyD88(-/-) mice were rendered susceptible to PcP by
      depletion of CD4(+) T cells. At 4 wk postinfection, CD4-depleted WT and MyD88(-/
      ) mice harbored similar organism burdens, but MyD88(-/-) mice were protected from
      the PcP-related respiratory impairment observed in WT mice. Improved pulmonary
      physiology in MyD88(-/-) mice correlated with lower lung CCL2 levels and reduced
      cell recruitment. However, by 5 wk postinfection, the overall health of MyD88(-/
      ) mice began to deteriorate rapidly relative to WT, with accelerated weight loss,
      impaired lung function, and exacerbated alveolar inflammation. This physiological
      decline of MyD88(-/-) mice was associated with increased TNF-alpha and IFN-gamma
      in the lung, and by the inability to control Pneumocystis burden. Thus, MyD88 is
      not required for resistance to Pneumocystis infection, but limits the adaptive
      immune response in immunocompetent mice. In the setting of active PcP, MyD88
      signaling contributes to both immunopathogenesis and control of fungal burden. 

PMID- 24293629
TI  - TGF-beta promotes immune responses in the presence of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) possess potent immunosuppression capacity and could
      exert strong therapeutic effects in many diseases, especially inflammatory
      disorders, in animal models and clinical settings. Although inflammatory
      cytokines are critical in inducing the immune modulatory properties of MSCs,
      detailed molecular mechanisms are yet to be fully understood. TGF-beta is a well
      known anti-inflammatory cytokine and exists in various inflammatory processes;
      therefore, we investigated whether it could synergize with MSCs in suppressing
      immune responses. To our surprise, we found that TGF-beta actually reversed the
      immunosuppressive effect of MSCs on anti-CD3 activated splenocytes. Using TGF
      beta unresponsive MSCs, we demonstrated that the TGF-beta directly acted on MSCs.
      Furthermore, we showed that the effect of TGF-beta is exerted through inhibiting
      inflammatory cytokines induced inducible NO synthase (iNOS) expression in a SMAD3
      dependent manner. Interestingly, we found that TGF-beta produced by MSCs could
      act in an autocrine manner to reduce inflammatory cytokine-induced inducible NO
      synthase expression by MSCs themselves. Therefore, our study revealed a
      previously unrecognized property of TGF-beta in promoting immune responses in the
      presence of MSCs. 

PMID- 24293630
TI  - Two separate defects affecting true naive or virtual memory T cell precursors
      combine to reduce naive T cell responses with aging.
AB  - Naive T cell responses are eroded with aging. We and others have recently shown
      that unimmunized old mice lose >= 70% of Ag-specific CD8 T cell precursors and
      that many of the remaining precursors acquire a virtual (central) memory (VM;
      CD44(hi)CD62L(hi)) phenotype. In this study, we demonstrate that unimmunized TCR
      transgenic (TCRTg) mice also undergo massive VM conversion with age, exhibiting
      rapid effector function upon both TCR and cytokine triggering. Age-related VM
      conversion in TCRTg mice directly depended on replacement of the original TCRTg
      specificity by endogenous TCRalpha rearrangements, indicating that TCR signals
      must be critical in VM conversion. Importantly, we found that VM conversion had
      adverse functional effects in both old wild-type and old TCRTg mice; that is, old
      VM, but not old true naive, T cells exhibited blunted TCR-mediated, but not IL-15
      mediated, proliferation. This selective proliferative senescence correlated with
      increased apoptosis in old VM cells in response to peptide, but decreased
      apoptosis in response to homeostatic cytokines IL-7 and IL-15. Our results
      identify TCR as the key factor in differential maintenance and function of Ag
      specific precursors in unimmunized mice with aging, and they demonstrate that two
      separate age-related defects--drastic reduction in true naive T cell precursors
      and impaired proliferative capacity of their VM cousins--combine to reduce naive
      T cell responses with aging.

PMID- 24293632
TI  - Lidocaine reduces neutrophil recruitment by abolishing chemokine-induced arrest
      and transendothelial migration in septic patients.
AB  - The inappropriate activation, positioning, and recruitment of leukocytes are
      implicated in the pathogenesis of multiple organ failure in sepsis. Although the
      local anesthetic lidocaine modulates inflammatory processes, the effects of
      lidocaine in sepsis are still unknown. This double-blinded, prospective,
      randomized clinical trial was conducted to investigate the effect of lidocaine on
      leukocyte recruitment in septic patients. Fourteen septic patients were
      randomized to receive either a placebo (n = 7) or a lidocaine (n = 7) bolus (1.5
      mg/kg), followed by continuous infusion (100 mg/h for patients >70 kg or 70 mg/h
      for patients <70 kg) over a period of 48 h. Selectin-mediated slow rolling,
      chemokine-induced arrest, and transmigration were investigated by using flow
      chamber and transmigration assays. Lidocaine treatment abrogated chemokine
      induced neutrophil arrest and significantly impaired neutrophil transmigration
      through endothelial cells by inhibition of the protein kinase C-theta while not
      affecting the selectin-mediated slow leukocyte rolling. The observed results were
      not attributable to changes in surface expression of adhesion molecules or
      selectin-mediated capturing capacity, indicating a direct effect of lidocaine on
      signal transduction in neutrophils. These data suggest that lidocaine selectively
      inhibits chemokine-induced arrest and transmigration of neutrophils by inhibition
      of protein kinase C-theta while not affecting selectin-mediated slow rolling.
      These findings may implicate a possible therapeutic role for lidocaine in
      decreasing the inappropriate activation, positioning, and recruitment of
      leukocytes during sepsis. 

PMID- 24293631
TI  - Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5.
AB  - There is intense interest in induction and characterization of strain
      transcending neutralizing Ab against antigenically variable human pathogens. We
      have recently identified the human malaria parasite Plasmodium falciparum
      reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly
      neutralizing Abs, but there is little information regarding the functional
      mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine
      induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to
      erythrocytes and are capable of blocking the interaction of PfRH5 with its
      receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence
      of the following: 1) the ability to block the PfRH5-basigin interaction in vitro
      is predictive of functional activity, but absence of blockade does not predict
      absence of functional activity; 2) neutralizing mAbs bind spatially related
      epitopes on the folded protein, involving at least two defined regions of the
      PfRH5 primary sequence; 3) a brief exposure window of PfRH5 is likely to
      necessitate rapid binding of Ab to neutralize parasites; and 4) intact bivalent
      IgG contributes to but is not necessary for parasite neutralization. These data
      provide important insight into the mechanisms of broadly neutralizing anti
      malaria Abs and further encourage anti-PfRH5-based malaria prevention efforts. 

PMID- 24293633
TI  - Helicobacter pylori cytotoxin-associated gene A impairs human dendritic cell
      maturation and function through IL-10-mediated activation of STAT3.
AB  - Helicobacter pylori infection induces chronic gastric inflammation that can
      progress to cancer. In this process, the virulence factor cytotoxin-associated
      gene A (CagA) plays a central role by directly altering epithelial cell signaling
      and inducing a strong Th1 immune response, which contributes to carcinogenesis.
      It is still barely understood how the bacterium evades clearance despite this
      solid immune response and persists lifelong. Dendritic cells (DCs) play a major
      role in determining the adaptive immune response toward H. pylori, and high
      levels of regulatory T cells have been detected infiltrating the gastric mucosa
      of H. pylori-infected patients, which contribute to bacterial persistence.
      Although murine studies indicate that H. pylori induces tolerization of DCs and
      impairs DC maturation, the virulence determinants involved are still
      controversial. Moreover, the signaling cascades engaged in human DC tolerization
      upon H. pylori infection remain unknown. In the current study, we analyzed the
      effect of H. pylori infection on human DC maturation and function, focusing on
      the virulence factors implicated and signaling pathways involved. Our results
      reveal that CagA is crucial for DC tolerization by modulating IL-10 secretion
      and, in turn, STAT3 phosphorylation, favoring a regulatory T cell immune
      response. Our findings help to unravel the paradox why CagA-positive strains,
      although eliciting a stronger inflammatory response, have overcome evolutionary
      pressure and persisted in their human host. 

PMID- 24293634
TI  - Immunotherapy with TCR-redirected T cells: comparison of TCR-transduced and TCR
      engineered hematopoietic stem cell-derived T cells.
AB  - Redirecting Ag specificity by transfer of TCR genes into PBLs is an attractive
      method to generate large numbers of cytotoxic T cells for immunotherapy of cancer
      and viral diseases. However, transferred TCR chains can pair with endogenous TCR
      chains, resulting in the formation of mispaired TCR dimers and decreased or
      unspecific reactivity. TCR gene transfer into hematopoietic stem cells (HSCs) is
      an alternative to create T cells with desired Ag specificity, because in this
      case expression of endogenous TCR chains is then less likely owing to allelic
      exclusion. We generated TCR-transduced T cells from peripheral T cells using the
      lymphocytic choriomeningitis virus-specific P14 TCR. After transfer of the P14
      TCR genes into HSCs and subsequent reconstitution of irradiated mice, TCR
      engineered HSC-derived T cells were produced. We then compared the Ag-specific T
      cell populations with P14 TCR-transgenic T cells for their therapeutic efficiency
      in three in vivo models. In this study, we demonstrate that TCR-transduced T
      cells and TCR-engineered HSC-derived T cells are comparable in controlling
      lymphocytic choriomeningitis virus infection in mice and suppress growth of B16
      tumor cells expressing the cognate Ag in a comparable manner. 

PMID- 24293635
TI  - Social networking sites: a clinical dilemma?
AB  - Social networking sites (SNS) are having an increasing influence on patients'
      lives and doctors are far from certain about how to deal with this new challenge.
      In our literature search, we could find no research on how doctors could engage
      positively with SNS to improve patient outcomes or create more patient-led care.
      We need to acknowledge the fact that a review of a patient's SNS page has the
      potential to enhance assessment and management, particularly where a corroborant
      history is hard to attain. As doctors, we need to think clearly about how to
      adapt our practice in light of this new form of communication; in particular,
      whether there is a case for engaging with SNS to improve patient care. 

PMID- 24293636
TI  - Rationing, inefficiency and the role of clinicians.

PMID- 24293637
TI  - Comparative analysis of microbiome between accurately identified 16S rDNA and
      quantified bacteria in simulated samples.
AB  - Although 16S rRNA gene (rDNA) sequencing is the gold standard for categorizing
      bacteria or characterizing microbial communities its clinical utility is limited
      by bias in metagenomic studies, in either the experiments or the data analyses.
      To evaluate the efficiency of current metagenomic methods, we sequenced seven
      simulated samples of ten bacterial species mixed at different concentrations. The
      V3 region of 16S rDNA was targeted and used to determine the distribution of
      bacterial species. The number of target sequences in individual simulated samples
      was in the range 1-1000 to provide a better reflection of natural microbial
      communities. However, for a given bacterial species present in the same
      proportion but at different concentrations, the observed percentage of 16S rDNAs
      was similar, except at very low concentrations that cannot be detected by real
      time PCR. These results confirmed that the comparative microbiome in a sample
      characterized by 16S rDNA sequencing is sufficient to detect not only potential
      infectious pathogens, but also the relative proportion of 16S rDNA in the sample.

PMID- 24293638
TI  - Detection of inducible clindamycin resistance in group B Streptococcus: does the
      distance between the disks matter?

PMID- 24293640
TI  - Endogenous beta-glucocerebrosidase activity in Abca12-/-epidermis elevates
      ceramide levels after topical lipid application but does not restore barrier
      function.
AB  - ABCA12 mutations disrupt the skin barrier and cause harlequin ichthyosis. We
      previously showed Abca12(-/-) skin has increased glucosylceramide (GlcCer) and
      correspondingly lower amounts of ceramide (Cer). To examine why loss of ABCA12
      leads to accumulation of GlcCer, de novo sphingolipid synthesis was assayed using
      [(14)C]serine labeling in ex vivo skin cultures. A defect was found in beta
      glucocerebrosidase (GCase) processing of newly synthesized GlcCer species. This
      was not due to a decline in GCase function. Abca12(-/-) epidermis had 5-fold more
      GCase protein (n = 4, P < 0.01), and a 5-fold increase in GCase activity (n = 3,
      P < 0.05). As with Abca12(+/+) epidermis, immunostaining in null skin showed a
      typical interstitial distribution of the GCase protein in the Abca12(-/-) stratum
      corneum. Hence, we tested whether the block in GlcCer conversion could be
      circumvented by topically providing GlcCer. This approach restored up to 15% of
      the lost Cer products of GCase activity in the Abca12(-/-) epidermis. However,
      this level of barrier ceramide replacement did not significantly reduce trans
      epidermal water loss function. Our results indicate loss of ABCA12 function
      results in a failure of precursor GlcCer substrate to productively interact with
      an intact GCase enzyme, and they support a model of ABCA12 function that is
      critical for transporting GlcCer into lamellar bodies. 

PMID- 24293639
TI  - Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2-/-
      lipodystrophic mice independent of hepatocyte leptin receptors.
AB  - Leptin is essential for energy homeostasis and regulation of food intake.
      Patients with congenital generalized lipodystrophy (CGL) due to mutations in 1
      acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) and the CGL murine model
      (Agpat2(-/-) mice) both have severe insulin resistance, diabetes mellitus,
      hepatic steatosis, and low plasma leptin levels. In this study, we show that
      continuous leptin treatment of Agpat2(-/-) mice for 28 days reduced plasma
      insulin and glucose levels and normalized hepatic steatosis and
      hypertriglyceridemia. Leptin also partially, but significantly, reversed the low
      plasma thyroxine and high corticosterone levels found in Agpat2(-/-) mice. Levels
      of carbohydrate response element binding protein (ChREBP) were reduced, whereas
      lipogenic gene expression were increased in the livers of Agpat2(-/-) mice,
      suggesting that deregulated ChREBP contributed to the development of fatty livers
      in these mice and that this transcription factor is a target of leptin's
      beneficial metabolic action. Leptin administration did not change hepatic fatty
      acid oxidation enzymes mRNA levels in Agpat2(-/-) mice. The selective deletion of
      leptin receptors only in hepatocytes did not prevent the positive metabolic
      actions of leptin in Agpat2(-/-) mice, supporting the notion that the majority of
      metabolic actions of leptin are dependent on its action in nonhepatocyte cells
      and/or the central nervous system.

PMID- 24293641
TI  - Cholesteryl ester transfer proteins from different species do not have equivalent
      activities.
AB  - Site-specific changes in the amino acid composition of human cholesteryl ester
      transfer protein (CETP) modify its preference for triglyceride (TG) versus
      cholesteryl ester (CE) as substrate. CETP homologs are found in many species but
      little is known about their activity. Here, we examined the lipid transfer
      properties of CETP species with 80-96% amino acid identity to human CETP. TG/CE
      transfer ratios for recombinant rabbit, monkey, and hamster CETPs were 1.40-,
      1.44-, and 6.08-fold higher than human CETP, respectively. In transfer assays
      between VLDL and HDL, net transfers of CE into VLDL by human and monkey CETPs
      were offset by equimolar net transfers of TG toward HDL. For hamster CETP this
      process was not equimolar but resulted in a net flow of lipid (TG) into HDL. When
      assayed for the ability to transfer lipid to an acceptor particle lacking CE and
      TG, monkey and hamster CETPs were most effective, although all CETP species were
      able to promote this one-way movement of neutral lipid. We conclude that CETPs
      from human, monkey, rabbit, and hamster are not functionally equivalent. Most
      unique was hamster CETP, which strongly prefers TG as a substrate and promotes
      the net flow of lipid from VLDL to HDL. 

PMID- 24293642
TI  - Role of D2 dopamine receptor in adrenal cortical cell proliferation and
      aldosterone-producing adenoma tumorigenesis.
AB  - Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia are the two
      characteristic types of primary aldosteronism. Dysregulation of adrenal cortical
      cell proliferation contributes to both diseases. We previously demonstrated that
      APA expressed less dopamine D2 receptor than the respective non-tumor tissue and
      might contribute to the overproduction of aldosterone. As activation of D2
      receptor inhibits the proliferation of various cells, downregulation of D2
      receptor in APA may play a role in the tumorigenesis of APA. In this study, we
      demonstrate that D2 receptor plays a role in angiotensin II (AII)-stimulated
      adrenal cortical cell proliferation. The D2 receptor agonist, bromocriptine,
      inhibited AII-stimulated cell proliferation in primary cultures of the normal
      human adrenal cortex and APA through attenuating AII-induced phosphorylation of
      PK-stimulated cyclin D1 protein expression and cell proliferation. D2 receptor
      also inhibited AII-induced ERK1/2 phosphorylation. Our results demonstrate that,
      in addition to inhibiting aldosterone synthesis/production, D2 receptor exerts an
      anti-proliferative effect in adrenal cortical and APA cells by attenuating PKCMU
      and ERK phosphorylation. The lower level of expression of D2 receptor in APA may
      augment cell proliferation and plays a crucial role in the tumorigenesis of APA.
      Our novel finding suggests a new therapeutic target for primary aldosteronism. 

PMID- 24293643
TI  - RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator
      nucleotide GTP to form a mechanistically important pre-initiation state.
AB  - Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the
      single-stranded RNA genome in the absence of a primer. The template sequence 5'
      CU-3' at the 3'-end of the flaviviral genome is highly conserved. Surprisingly,
      flaviviral RdRps require high concentrations of the second incoming nucleotide
      GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP
      stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp)
      also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for
      specific recognition of GTP. Comparison of the jRdRpGTP structure with other
      viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo
      jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple
      conformations in absence of GTP. Motif F becomes ordered on GTP binding and
      occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key
      residues that interact with GTP evinces that the jRdRpGTP structure represents a
      novel pre-initiation state. Also, binding studies show that GTP binding reduces
      affinity of RdRp for RNA, but the presence of the catalytic Mn(2+) ion abolishes
      this inhibition. Collectively, these observations suggest that the observed pre
      initiation state may serve as a checkpoint to prevent erroneous template
      independent RNA synthesis by jRdRp during initiation. 

PMID- 24293644
TI  - Structural mechanism of transcription regulation of the Staphylococcus aureus
      multidrug efflux operon mepRA by the MarR family repressor MepR.
AB  - The multidrug efflux pump MepA is a major contributor to multidrug resistance in
      Staphylococcus aureus. MepR, a member of the multiple antibiotic resistance
      regulator (MarR) family, represses mepA and its own gene. Here, we report the
      structure of a MepR-mepR operator complex. Structural comparison of DNA-bound
      MepR with 'induced' apoMepR reveals the large conformational changes needed to
      allow the DNA-binding winged helix-turn-helix motifs to interact with the
      consecutive major and minor grooves of the GTTAG signature sequence.
      Intriguingly, MepR makes no hydrogen bonds to major groove nucleobases. Rather,
      recognition-helix residues Thr60, Gly61, Pro62 and Thr63 make sequence-specifying
      van der Waals contacts with the TTAG bases. Removing these contacts dramatically
      affects MepR-DNA binding activity. The wings insert into the flanking minor
      grooves, whereby residue Arg87, buttressed by Asp85, interacts with the O2 of T4
      and O4' ribosyl oxygens of A23 and T4. Mutating Asp85 and Arg87, both conserved
      throughout the MarR family, markedly affects MepR repressor activity. The
      His14':Arg59 and Arg10':His35:Phe108 interaction networks stabilize the DNA
      binding conformation of MepR thereby contributing significantly to its high
      affinity binding. A structure-guided model of the MepR-mepA operator complex
      suggests that MepR dimers do not interact directly and cooperative binding is
      likely achieved by DNA-mediated allosteric effects. 

PMID- 24293645
TI  - STITCH 4: integration of protein-chemical interactions with user data.
AB  - STITCH is a database of protein-chemical interactions that integrates many
      sources of experimental and manually curated evidence with text-mining
      information and interaction predictions. Available at http://stitch.embl.de, the
      resulting interaction network includes 390 000 chemicals and 3.6 million proteins
      from 1133 organisms. Compared with the previous version, the number of high
      confidence protein-chemical interactions in human has increased by 45%, to 367
      000. In this version, we added features for users to upload their own data to
      STITCH in the form of internal identifiers, chemical structures or quantitative
      data. For example, a user can now upload a spreadsheet with screening hits to
      easily check which interactions are already known. To increase the coverage of
      STITCH, we expanded the text mining to include full-text articles and added a
      prediction method based on chemical structures. We further changed our scheme for
      transferring interactions between species to rely on orthology rather than
      protein similarity. This improves the performance within protein families, where
      scores are now transferred only to orthologous proteins, but not to paralogous
      proteins. STITCH can be accessed with a web-interface, an API and downloadable
      files. 

PMID- 24293646
TI  - DNA binding properties of human Cdc45 suggest a function as molecular wedge for
      DNA unwinding.
AB  - The cell division cycle protein 45 (Cdc45) represents an essential replication
      factor that, together with the Mcm2-7 complex and the four subunits of GINS,
      forms the replicative DNA helicase in eukaryotes. Recombinant human Cdc45
      (hCdc45) was structurally characterized and its DNA-binding properties were
      determined. Synchrotron radiation circular dichroism spectroscopy, dynamic light
      scattering, small-angle X-ray scattering and atomic force microscopy revealed
      that hCdc45 exists as an alpha-helical monomer and possesses a structure similar
      to its bacterial homolog RecJ. hCdc45 bound long (113-mer or 80-mer) single
      stranded DNA fragments with a higher affinity than shorter ones (34-mer). hCdc45
      displayed a preference for 3' protruding strands and bound tightly to single
      strand/double-strand DNA junctions, such as those presented by Y-shaped DNA,
      bubbles and displacement loops, all of which appear transiently during the
      initiation of DNA replication. Collectively, our findings suggest that hCdc45 not
      only binds to but also slides on DNA with a 3'-5' polarity and, thereby acts as a
      molecular 'wedge' to initiate DNA strand displacement. 

PMID- 24293647
TI  - ASD v2.0: updated content and novel features focusing on allosteric regulation.
AB  - Allostery is the most direct and efficient way for regulation of biological
      macromolecule function and is induced by the binding of a ligand at an allosteric
      site topographically distinct from the orthosteric site. AlloSteric Database
      (ASD, http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive
      information on allostery. Owing to the inherent high receptor selectivity and
      lower target-based toxicity, allosteric regulation is expected to assume a more
      prominent role in drug discovery and bioengineering, leading to the rapid growth
      of allosteric findings. In this updated version, ASD v2.0 has expanded to 1286
      allosteric proteins, 565 allosteric diseases and 22 008 allosteric modulators. A
      total of 907 allosteric site-modulator structural complexes and >200 structural
      pairs of orthosteric/allosteric sites in the allosteric proteins were constructed
      for researchers to develop allosteric site and pathway tools in response to
      community demands. Up-to-date allosteric pathways were manually curated in the
      updated version. In addition, both the front-end and the back-end of ASD have
      been redesigned and enhanced to allow more efficient access. Taken together,
      these updates are useful for facilitating the investigation of allosteric
      mechanisms, allosteric target identification and allosteric drug discovery. 

PMID- 24293649
TI  - The SILVA and "All-species Living Tree Project (LTP)" taxonomic frameworks.
AB  - SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive
      resource for up-to-date quality-controlled databases of aligned ribosomal RNA
      (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and
      supplementary online services. SILVA provides a manually curated taxonomy for all
      three domains of life, based on representative phylogenetic trees for the small-
      and large-subunit rRNA genes. This article describes the improvements the SILVA
      taxonomy has undergone in the last 3 years. Specifically we are focusing on the
      curation process, the various resources used for curation and the comparison of
      the SILVA taxonomy with Greengenes and RDP-II taxonomies. Our comparisons not
      only revealed a reasonable overlap between the taxa names, but also points to
      significant differences in both names and numbers of taxa between the three
      resources. 

PMID- 24293648
TI  - Differential contribution of basic residues to HIV-1 nucleocapsid protein's
      nucleic acid chaperone function and retroviral replication.
AB  - The human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein
      contains 15 basic residues located throughout its 55-amino acid sequence, as well
      as one aromatic residue in each of its two CCHC-type zinc finger motifs. NC
      facilitates nucleic acid (NA) rearrangements via its chaperone activity, but the
      structural basis for this activity and its consequences in vivo are not
      completely understood. Here, we investigate the role played by basic residues in
      the N-terminal domain, the N-terminal zinc finger and the linker region between
      the two zinc fingers. We use in vitro ensemble and single-molecule DNA stretching
      experiments to measure the characteristics of wild-type and mutant HIV-1 NC
      proteins, and correlate these results with cell-based HIV-1 replication assays.
      All of the cationic residue mutations lead to NA interaction defects, as well as
      reduced HIV-1 infectivity, and these effects are most pronounced on neutralizing
      all five N-terminal cationic residues. HIV-1 infectivity in cells is correlated
      most strongly with NC's NA annealing capabilities as well as its ability to
      intercalate the DNA duplex. Although NC's aromatic residues participate directly
      in DNA intercalation, our findings suggest that specific basic residues enhance
      these interactions, resulting in optimal NA chaperone activity. 

PMID- 24293650
TI  - The output of the tRNA modification pathways controlled by the Escherichia coli
      MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species.
AB  - In Escherichia coli, the MnmEG complex modifies transfer RNAs (tRNAs) decoding
      NNA/NNG codons. MnmEG catalyzes two different modification reactions, which add
      an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the
      anticodon wobble uridine using ammonium or glycine, respectively. In
      tRNA(cmnm5s2UUG)(Gln) and tRNA(cmnm5UmAA)(Leu), however, cmnm(5) appears as the
      final modification, whereas in the remaining tRNAs, the MnmEG products are
      converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional
      enzyme MnmC. MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts
      nm(5) into mnm(5), thus producing an atypical network of modification pathways.
      We investigate the activities and tRNA specificity of MnmEG and the MnmC domains,
      the ability of tRNAs to follow the ammonium or glycine pathway and the effect of
      mnmC mutations on growth. We demonstrate that the two MnmC domains function
      independently of each other and that tRNA(cmnm5s2UUG)(Gln) and
      tRNA(cmnm5UmAA)(Leu), are substrates for MnmC(m), but not MnmC(o). Synthesis of
      mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in
      tRNA(mnm5s2UUU)(Lys). We also show that MnmEG can modify all the tRNAs via the
      ammonium pathway. Strikingly, the net output of the MnmEG pathways in vivo
      depends on growth conditions and tRNA species. Loss of any MnmC activity has a
      biological cost under specific conditions.

PMID- 24293651
TI  - Conformations of p53 response elements in solution deduced using site-directed
      spin labeling and Monte Carlo sampling.
AB  - The tumor suppressor protein p53 regulates numerous signaling pathways by
      specifically recognizing diverse p53 response elements (REs). Understanding the
      mechanisms of p53-DNA interaction requires structural information on p53 REs.
      However, such information is limited as a 3D structure of any RE in the unbound
      form is not available yet. Here, site-directed spin labeling was used to probe
      the solution structures of REs involved in p53 regulation of the p21 and Bax
      genes. Multiple nanometer distances in the p21-RE and BAX-RE, measured using a
      nucleotide-independent nitroxide probe and double-electron-electron-resonance
      spectroscopy, were used to derive molecular models of unbound REs from pools of
      all-atom structures generated by Monte-Carlo simulations, thus enabling analyses
      to reveal sequence-dependent DNA shape features of unbound REs in solution. The
      data revealed distinct RE conformational changes on binding to the p53 core
      domain, and support the hypothesis that sequence-dependent properties encoded in
      REs are exploited by p53 to achieve the energetically most favorable mode of
      deformation, consequently enhancing binding specificity. This work reveals
      mechanisms of p53-DNA recognition, and establishes a new
      experimental/computational approach for studying DNA shape in solution that has
      far-reaching implications for studying protein-DNA interactions. 

PMID- 24293652
TI  - Novel method for site-specific induction of oxidative DNA damage reveals
      differences in recruitment of repair proteins to heterochromatin and euchromatin.
AB  - Reactive oxygen species (ROS)-induced DNA damage is repaired by the base excision
      repair pathway. However, the effect of chromatin structure on BER protein
      recruitment to DNA damage sites in living cells is poorly understood. To address
      this problem, we developed a method to specifically produce ROS-induced DNA
      damage by fusing KillerRed (KR), a light-stimulated ROS-inducer, to a tet
      repressor (tetR-KR) or a transcription activator (TA-KR). TetR-KR or TA-KR, bound
      to a TRE cassette (~ 90 kb) integrated at a defined genomic locus in U2OS cells,
      was used to induce ROS damage in hetero- or euchromatin, respectively. We found
      that DNA glycosylases were efficiently recruited to DNA damage in
      heterochromatin, as well as in euchromatin. PARP1 was recruited to DNA damage
      within condensed chromatin more efficiently than in active chromatin. In
      contrast, recruitment of FEN1 was highly enriched at sites of DNA damage within
      active chromatin in a PCNA- and transcription activation-dependent manner. These
      results indicate that oxidative DNA damage is differentially processed within
      hetero or euchromatin.

PMID- 24293653
TI  - ARF induction in response to DNA strand breaks is regulated by PARP1.
AB  - The ARF tumour suppressor protein, the gene of which is frequently mutated in
      many human cancers, plays an important role in the cellular stress response by
      orchestrating up-regulation of p53 protein and consequently promoting cell-cycle
      delay. Although p53 protein function has been clearly linked to the cellular DNA
      damage response, the role of ARF protein in this process is unclear. Here, we
      report that arf gene transcription is induced by DNA strand breaks (SBs) and that
      ARF protein accumulates in response to persistent DNA damage. We discovered that
      poly(ADP-ribose) synthesis catalysed by PARP1 at the sites of unrepaired SBs
      activates ARF transcription through a protein signalling cascade, including the
      NAD(+)-dependent deacetylase SIRT1 and the transcription factor E2F1. Our data
      suggest that poly(ADP-ribose) synthesis at the sites of SBs initiates DNA damage
      signal transduction by reducing the cellular concentration of NAD(+), thus down
      regulating SIRT1 activity and consequently activating E2F1-dependent ARF
      transcription. Our findings suggest a vital role for ARF in DNA damage
      signalling, and furthermore explain the critical requirement for ARF inactivation
      in cancer cells, which are frequently deficient in DNA repair and accumulate DNA
      damage. 

PMID- 24293654
TI  - The SEED and the Rapid Annotation of microbial genomes using Subsystems
      Technology (RAST).
AB  - In 2004, the SEED (http://pubseed.theseed.org/) was created to provide consistent
      and accurate genome annotations across thousands of genomes and as a platform for
      discovering and developing de novo annotations. The SEED is a constantly updated
      integration of genomic data with a genome database, web front end, API and server
      scripts. It is used by many scientists for predicting gene functions and
      discovering new pathways. In addition to being a powerful database for
      bioinformatics research, the SEED also houses subsystems (collections of
      functionally related protein families) and their derived FIGfams (protein
      families), which represent the core of the RAST annotation engine
      (http://rast.nmpdr.org/). When a new genome is submitted to RAST, genes are
      called and their annotations are made by comparison to the FIGfam collection. If
      the genome is made public, it is then housed within the SEED and its proteins
      populate the FIGfam collection. This annotation cycle has proven to be a robust
      and scalable solution to the problem of annotating the exponentially increasing
      number of genomes. To date, >12 000 users worldwide have annotated >60 000
      distinct genomes using RAST. Here we describe the interconnectedness of the SEED
      database and RAST, the RAST annotation pipeline and updates to both resources. 

PMID- 24293655
TI  - Poly(A) RNA and Paip2 act as allosteric regulators of poly(A)-binding protein.
AB  - When bound to the 3' poly(A) tail of mRNA, poly(A)-binding protein (PABP)
      modulates mRNA translation and stability through its association with various
      proteins. By visualizing individual PABP molecules in real time, we found that
      PABP, containing four RNA recognition motifs (RRMs), adopts a conformation on
      poly(A) binding in which RRM1 is in proximity to RRM4. This conformational change
      is due to the bending of the region between RRM2 and RRM3. PABP-interacting
      protein 2 actively disrupts the bent structure of PABP to the extended structure,
      resulting in the inhibition of PABP-poly(A) binding. These results suggest that
      the changes in the configuration of PABP induced by interactions with various
      effector molecules, such as poly(A) and PABP-interacting protein 2, play pivotal
      roles in its function. 

PMID- 24293656
TI  - SCOP2 prototype: a new approach to protein structure mining.
AB  - We present a prototype of a new structural classification of proteins, SCOP2
      (http://scop2.mrc-lmb.cam.ac.uk/), that we have developed recently. SCOP2 is a
      successor to the Structural Classification of Proteins (SCOP, http://scop.mrc
      lmb.cam.ac.uk/scop/) database. Similarly to SCOP, the main focus of SCOP2 is to
      organize structurally characterized proteins according to their structural and
      evolutionary relationships. SCOP2 was designed to provide a more advanced
      framework for protein structure annotation and classification. It defines a new
      approach to the classification of proteins that is essentially different from
      SCOP, but retains its best features. The SCOP2 classification is described in
      terms of a directed acyclic graph in which nodes form a complex network of many
      to-many relationships and are represented by a region of protein structure and
      sequence. The new classification project is expected to ensure new advances in
      the field and open new areas of research. 

PMID- 24293657
TI  - Planar cell polarity and the kidney.
AB  - Planar cell polarity (PCP) is the uniform orientation and alignment of a group of
      cells orthogonal to the apical-basal axis within a tissue. Originally described
      in insects, it is now known that PCP is required for many processes in
      vertebrates, including directional cell movement, polarized cell division,
      ciliary orientation, neural tube closure, heart development and lung branching.
      In this review, we outline the evidence implicating PCP in kidney development and
      disease focusing initially on the function of PCP in ureteric bud branching and
      elongation. We then describe how defects in PCP may lead to polycystic kidney
      disease and discuss a newly identified role for PCP in the kidney filtration
      barrier. 

PMID- 24293659
TI  - International variation in classification of dialysis withdrawal: a systematic
      review.
AB  - BACKGROUND AND OBJECTIVES: In patients with end-stage renal disease (ESRD), the
      rate of deaths preceded by dialysis withdrawal is high. However, rates vary
      across studies and national renal registries. This study aimed to (i) determine
      how dialysis withdrawal mortality is defined in the literature and (ii) whether
      mortality rates preceded by dialysis withdrawal change over time. METHODS:
      MEDLINE (1946 to March 2012) and EMBASE (1980 to March 2012) databases were
      searched. We included epidemiological studies that reported data permitting
      calculation of crude (unadjusted) mortality rates preceded by dialysis
      withdrawal. Definitions of dialysis withdrawal were also extracted. Crude
      mortality rates and 95% confidence intervals were calculated using OpenEpi
      software. Non-English language studies were excluded. RESULTS: Twenty-three
      eligible studies were identified; these included 14 527 885 dialysis patients at
      risk from six countries. Crude mortality rates preceded by dialysis withdrawal
      ranged from 3 to 50.2 per 1000 person-years. Seven different definitions of
      dialysis withdrawal were identified, with no assessment of validity. Crude
      mortality rates preceded by withdrawal have increased over time across the study
      period 1966 (3 per 1000 person-years) to 2010 (48.6 per 1000 person-years),
      although these rates are difficult to interpret because of differences in
      classification. In the USA crude mortality rates preceded by dialysis withdrawal
      are higher in the older population and have increased over time in the age group
      65+ years. In this age group, the crude mortality rate preceded by dialysis
      withdrawal was 89.4 per 1000 person-years (2008-10) compared with 26.1 per 1000
      person-years in the age group 50-64 years (2008-10). CONCLUSION: Mortality rates
      preceded by dialysis withdrawal over time should be interpreted with caution
      because of differences in classification. Types of dialysis withdrawal need more
      careful elucidation, and we propose a unified classification of dialysis
      withdrawal based on trajectories and causal criteria.

PMID- 24293658
TI  - Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France:
      outcome with eculizumab.
AB  - BACKGROUND: An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin
      secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts
      occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all
      patients were treated with the monoclonal anti-C5 antibody, eculizumab. METHODS:
      The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and
      acute kidney injury. Data were obtained from initial gastrointestinal symptoms to
      the end of follow-up 10 weeks after the start of eculizumab. RESULTS: Among 24
      cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and
      one child), 6 (median; range 3-12) days after digestive symptoms begun. The
      median (range) highest or lowest biological values were platelet count 26 (range
      14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L;
      creatinine 152 (range 48-797) umol/L. All patients had extra-renal complications
      (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one
      was ventilated. After failure of plasma exchange to increase platelets in the
      first three patients, eculizumab was administered in all nine patients, 0-4 days
      after HUS diagnosis (median 1 day). One patient with very severe neurological HUS
      received immunoadsorption. Outcome was favourable in all patients, with rapid
      normalization of haemoglobin, platelets, LDH levels, renal function and
      neurological improvement. There were no deaths and no serious adverse events
      related to eculizumab. CONCLUSIONS: Early treatment of O104:H4 STEC-HUS by
      eculizumab was associated with a rapid and efficient recovery. Controlled
      prospective evaluation of eculizumab in STEC-HUS is warranted.

PMID- 24293660
TI  - A randomized controlled trial evaluating the erythropoiesis stimulating agent
      sparing potential of a vitamin E-bonded polysulfone dialysis membrane.
AB  - BACKGROUND: Vitamin E (VE) bonded polysulfone dialysis membranes have putative
      erythropoiesis stimulating agent (ESA)-sparing and anti-inflammatory properties
      based on data from a small number of studies. We sought to investigate this in a
      large, prospective 12-month randomized controlled trial. METHODS: Two-hundred and
      sixty prevalent haemodialysis (HD) patients were randomized to dialysis with VE
      bonded polysulfone membranes or non-VE-bonded equivalents. All ESA-dosing was
      performed by means of a computer-based anaemia management decision support
      system. Monthly data were used to calculate the ESA resistance index (ERI) and
      blood tests were performed at baseline, 6 and 12 months for measurement of C
      reactive protein (CRP) levels. RESULTS: Of the 260 patients, 123 were randomized
      to dialysis with the VE-membrane and 12-month data was available for 220
      patients. At the study population level, no beneficial effect of the VE membranes
      on the ERI or CRP levels was observed. Post hoc analyses indicated that there was
      a significant fall in ERI for patients with the highest baseline ESA resistance
      dialysed with the VE (9.28 [7.70-12.5] versus 7.70 [5.34-12.7] IU/week/kg/g/dL
      Hb, P = 0.01) but not the control membranes (9.45 [7.62-12.3] versus 8.14 [4.44
      15.6] IU/week/kg/g/dL Hb, P = 0.41); this was not attributable to changes in CRP
      levels. CONCLUSIONS: Wholesale switching of all chronic HD patients to dialysis
      with VE-bonded polysulfone membranes appears not to be associated with
      improvements in ESA-responsiveness or CRP. These membranes may have utility in
      patients with heightened ESA resistance.

PMID- 24293662
TI  - Peritoneal dialysis-related peritonitis with Acinetobacter baumannii: a review of
      seven cases.
AB  - Peritonitis is still known as an important complication of continuous ambulatory
      peritoneal dialysis (CAPD). Multi-drug resistant (MDR) Acinetobacter baumannii is
      an increasing problem worldwide. Moreover, the increasing reports of carbapenem
      resistant A. baumannii strains is common. Although peritoneal dialysis-related
      peritonitis with MDR A. baumannii is rarely reported, infection with this
      organism always results in serious peritonitis and increases the possibility of
      dropout or mortality. Here, we present 7 cases of peritonitis caused by A.
      baumannii species. Among those 7 cases, 2 involved MDR A. baumannii, and 1
      involved a carbapenem-resistant strain. All the MDR bacterial infections failed
      treatment. We also review the literature about Acinetobacter peritonitis and
      current treatment protocols. 

PMID- 24293663
TI  - Clinical outcomes in elderly patients on chronic peritoneal dialysis: a
      retrospective study from a single center in china.
AB  - OBJECTIVES: We aimed to evaluate clinical outcomes and identify the predictors of
      mortality in elderly patients undergoing continuous ambulatory peritoneal
      dialysis (CAPD). METHODS: This retrospective cohort study included all incident
      CAPD patients treated at our center from 2006 to 2009. Demographic and clinical
      data on initiation of CAPD and clinical events during the study period were
      collected. Survival probabilities were generated using the Kaplan-Meier method,
      and risk factors for mortality were evaluated using Cox proportional hazards
      models. RESULTS: Of 805 patients on CAPD, the elderly group (>=65 years; mean
      age: 71.3 +/- 4.3 years) consisted of 148 patients, and the younger group (<65
      years; mean age: 43.1 +/- 12.2years) consisted of 657 patients. The 1-, 2-, 3-,
      and 5-year patient survival rates were 97%, 92%, 88%, and 73% for the younger
      group, and 79%, 67%, 56%, and 30% for elderly group. The patient survival rates
      were significantly lower for the elderly group than for the younger group (p =
      0.000). However, technique survival did not significantly differ between the
      groups (p = 0.559). In the patients overall, the independent predictors of death
      were old age (p = 0.003), diabetes (p = 0.000), cardiovascular disease (p =
      0.006), lower hemoglobin (p = 0.010), and lower serum albumin (p = 0.024).
      Mortality in the elderly patients was associated with advanced age [relative risk
      (RR): 1.088; 95% confidence interval (CI): 1.027 to 1.153; p = 0.004], diabetes
      (RR: 2.064; 95% CI: 1.236 to 3.445; p = 0.006), and lower serum albumin (RR:
      0.940; 95% CI: 0.897 to 0.985; p = 0.010). CONCLUSIONS: The elderly patients on
      CAPD experienced technique survival comparable with that of younger patients, but
      their patient survival was lower. In elderly patients, mortality was determined
      predominantly by greater age, diabetes, and lower serum albumin. Our results
      indicate that chronic peritoneal dialysis is a viable dialysis option for elderly
      patients with end-stage renal disease. Better management of hypoalbuminemia and
      comorbid conditions might improve survival in elderly PD patients.

PMID- 24293664
TI  - Differences in coagulation between hemodialysis and peritoneal dialysis.
AB  - BACKGROUND: End-stage renal disease patients have significant cardiovascular
      morbidity and mortality, but little is known about differences in coagulation
      profiles between patients on hemodialysis (HD) and on peritoneal dialysis (PD).
      Given their long-term exposure to glucose-based dialysate, patients on PD can
      experience metabolic derangements. Theoretically, that exposure should create a
      more prothrombotic environment than occurs in HD patients. The objective of the
      present study was to quantify potential differences in baseline coagulation
      between PD and HD patients. ? METHODS: Our single-center cross-sectional study at
      a large academic health science center enrolled 50 age-, race-, and sex-matched
      subjects (10 control subjects, 20 HD patients, and 20 PD patients). Measurements
      included platelet function, platelet receptor distribution, and coagulation
      dynamics by thromboelastography and Hemodyne hemostasis assay (Hemodyne,
      Richmond, VA, USA). ? RESULTS: Compared with healthy control subjects, patients
      on both forms of dialysis showed prothrombotic coagulation protein profiles. The
      tissue-factor pathway was markedly elevated in both groups, but PD was associated
      with significantly greater concentrations of tissue factor (p = 0.0056) and
      tissue-factor pathway inhibitor (p = 0.0138). Similarly, compared with patients
      receiving HD, patients on PD had greater concentrations of fibrinogen (p =
      0.0325), which corresponded with platelet hyperfunction as measured by platelet
      contractile force and clot elastic modulus (p = 0.003 and 0.017 respectively,
      compared with values in HD patients). Platelet receptor distribution was similar
      between the groups. ? CONCLUSIONS: Compared with patients on HD, patients on PD
      appear to have a more prothrombotic profile. The clinical relevance of these
      findings needs to be studied in a prospective manner.

PMID- 24293665
TI  - The impact of transfer from hemodialysis on peritoneal dialysis technique
      survival.
AB  - BACKGROUND: A significant proportion of peritoneal dialysis (PD) patients receive
      an initial period of hemodialysis (HD) before transitioning to PD ("PD-switch").
      We sought to better understand the risks of PD technique failure (TF) and
      mortality for those patients compared with patients starting with PD as their
      first dialysis modality ("PD-first"). METHODS: Using Canadian Organ Replacement
      Register data, we compared the risk of PD TF between PD-first and PD-switch
      patients within the first year after HD initiation. In a secondary analysis, the
      PD-switch patients were stratified into three groups based on timing of the
      switch from initial HD to PD as follows: 0 - 90 days, 91 - 180 days, and 181 -
      365 days. Each group was compared with PD-first patients for risk of PD TF and
      death. RESULTS: Between 2001 and 2010, 9404 patients initiated PD as their first
      renal replacement therapy, and 3757 switched from HD to PD. After multivariable
      adjustment, the risk of PD TF was higher among PD-switch patients than among PD
      first patients [adjusted hazard ratio (AHR): 1.37; 95% confidence interval (CI):
      1.26 to 1.49], particularly within the first year after the switch from HD to PD
      (AHR: 1.51; 95% CI: 1.36 to 1.68). There was no association between time on HD
      within the first year and subsequent risk of PD TF. For all the stratified PD
      switch groups, death rates were higher than those for PD-first patients.
      CONCLUSIONS: Compared with patients who start renal replacement therapy with PD,
      those who transfer from HD to PD within the first year on dialysis experience
      higher rates of PD TF and death, with the highest risk being observed in the
      initial year after the switch to PD.

PMID- 24293669
TI  - Veterinary schools and satellite clinics.

PMID- 24293668
TI  - In defence of the veterinary profession.

PMID- 24293666
TI  - High glucose concentrations in peritoneal dialysate are associated with all-cause
      and cardiovascular disease mortality in continuous ambulatory peritoneal dialysis
      patients.
AB  - BACKGROUND: The effect of high peritoneal dialysate glucose concentration (PDGC)
      on all-cause and cardiovascular disease (CVD) mortality in peritoneal dialysis
      (PD) patients is unclear. OBJECTIVE: Our study aimed to investigate the effect of
      high PDGC on all-cause and CVD mortality in continuous ambulatory PD (CAPD)
      patients. METHODS: The study enrolled 716 patients newly initiated on CAPD
      therapy between January 2006 and December 2010. We allocated the patients to low
      (< 1.56%), medium (>= 1.56% to < 1.74%), and high (>= 1.74%) average PDGC groups
      according to the tertile of average PDGC in the first 6 months after PD
      initiation. Cox regression and ordinal logistic regression were used to analyze
      determinants of mortality and of PDGC use respectively. RESULTS: Mean follow-up
      in the study cohort was 31 +/- 15 months. The all-cause mortality was 4.7 events
      per 100 patient-years, and the leading cause of death was CVD. Patients with a
      higher PDGC had significantly higher cumulative rates of all-cause (log-rank p <
      0.001) and CVD mortality (log-rank p < 0.001). In Cox regression analysis, high
      PDGC independently predicted higher all-cause (hazard ratio: 2.63; p = 0.004) and
      CVD mortality (hazard ratio: 2.78; p = 0.01). Compared with a lower PDGC, a
      higher PDGC was significantly associated with older age [odds ratio (OR): 1.02; p
      < 0.001], low residual renal function (OR: 0.91; p < 0.001), and high dialysate
      to-plasma ratio of creatinine (OR: 28.61; p < 0.001) in ordinal logistic
      regression. CONCLUSIONS: Higher PDGC is associated with higher allcause and CVD
      mortality in CAPD patients.

PMID- 24293670
TI  - An ethicist's commentary on interdicting sick pigs at the border.

PMID- 24293671
TI  - A retrospective study of non-suppurative encephalitis in beef cattle from western
      Canada.
AB  - Non-suppurative encephalitis occurs sporadically in beef cattle in western
      Canada, leading to loss of animals. This retrospective study investigated the
      presence of viral, bacterial, and protozoal antigens or DNA in 37 western
      Canadian feedlot cattle with non-suppurative encephalitis for which a cause had
      not been identified. Cases were selected based on the age of the animal (> 7
      months), and clinical history of recumbency and depression. The identification of
      rabies in 1 case stresses the importance of including this viral disease in the
      list of differential diagnoses. Because there was variation in the severity,
      distribution, and type of lesions, it is possible that there may be more than 1
      cause, but failure to identify an infectious agent might also suggest that non
      infectious agents could play a role. 

PMID- 24293672
TI  - Myelomeningocoele and a dermoid sinus-like lesion in a French bulldog.
AB  - A 2-year-old male French bulldog was presented for investigation of lumbosacral
      pain and hindlimb ataxia associated with urinary and fecal incontinence. Survey
      radiography, myelography, and computed tomography images were suggestive of a
      dermoid sinus with associated spina bifida. Surgical intervention led to a
      resolution of pain and neurological deficits. Histopathological analysis of the
      excised tissue was compatible with a myelomeningocoele of the 7th lumbar
      vertebra. 

PMID- 24293673
TI  - Use of lomustine (CCNU) in a case of cutaneous equine lymphoma.
AB  - A 12-year-old gelding was diagnosed with recurrent lymphoma in multiple cutaneous
      sites. A highly invasive preputial mass caused urethral obstruction. The horse
      was treated with surgery and chemotherapy consisting of lomustine (CCNU) and
      prednisolone. The treatment was well-tolerated and effective. This is the first
      reported use of lomustine (CCNU) in a horse for the treatment of equine lymphoma.

PMID- 24293674
TI  - Ultrasound-guided percutaneous antegrade hydropropulsion to relieve ureteral
      obstruction in a pet guinea pig (Cavia porcellus).
AB  - Severe hydroureter and hydronephrosis secondary to ureteral obstruction by
      calculus were present in a guinea pig. A palliative ultrasound-guided
      percutaneous antegrade hydropropulsion was performed under general anesthesia to
      relieve the ureteral obstruction and the associated clinical signs. We describe
      the technique and the considerations for its potential application in similar
      cases. 

PMID- 24293675
TI  - The effect of antimicrobial treatment and preventive strategies on bovine
      respiratory disease and genetic relatedness and antimicrobial resistance of
      Mycoplasma bovis isolates in a western Canadian feedlot.
AB  - Feedlot calves (n = 3784) were systematically randomized and allocated in a 2 * 2
      factorial study to receive metaphylactic oxytetracycline (OTC) on arrival or no
      antimicrobial, as well as florfenicol once subcutaneously or twice
      intramuscularly (48 h apart) if diagnosed with bovine respiratory disease (BRD).
      Calves of different treatment groups were comingled and followed from placement
      to re-implantation (~100 days). Animals receiving OTC had a reduced risk of BRD,
      an increased risk of arthritis, and no significant differences in average daily
      gain, BRD relapse, overall mortality, or BRD mortality. There were no significant
      differences between treatment protocols. Deep nasal swabs (n = 233) taken at
      arrival (n = 122), treatment (n = 77), and swabs from lungs and joints at
      postmortem (n = 34) were cultured for Mycoplasma bovis from 61 animals ill or
      dying of chronic pneumonia and arthritis and from 61 healthy calves. There was
      significant variation in diversity among isolates (n = 51) between study years
      and different cattle. Metaphylaxis or antimicrobial treatment did not affect the
      diversity of isolates. Except for tilmicosin, isolates were largely susceptible
      to tested antimicrobials. 

PMID- 24293677
TI  - Trends in antimicrobial use in Marine Harvest Canada farmed salmon production in
      British Columbia (2003-2011).
AB  - Marine Havest Canada has significantly reduced its antimicrobial usage in salmon
      farming over the last 8 years. Change has come about largely through improvements
      in production, health management, and livestock selection. However, antimicrobial
      treatments are still required for stomatitis and bacterial kidney disease. Lack
      of efficacious vaccines and the limited number of licensed antimicrobials
      available to the industry continue to be of concern. 

PMID- 24293676
TI  - Evaluation of bacterial contamination on surgical drapes following use of the
      Bair Hugger((r)) forced air warming system.
AB  - This pilot study determined the rate of bacterial contamination on surgical
      drapes of small animal patients warmed intra-operatively with the Bair
      Hugger((r)) forced air warming system compared to a control method. Surgical
      drapes of 100 patients undergoing clean surgical procedures were swabbed with
      aerobic culturettes at the beginning and end of surgery. Samples were cultured on
      Trypticase soy agar. Contamination of the surgical drapes was identified in 6/98
      cases (6.1%). There was no significant difference in the number of contaminated
      surgical drapes between the Bair Hugger((r)) and control groups (P = 0.47). 

PMID- 24293678
TI  - Use of pimobendan in feline congenital heart failure.
AB  - A 6-month-old domestic shorthair cat was referred for evaluation of sudden
      lethargy and tachypnea following ovariohysterectomy. Upon failure of improvement
      with supportive care, a cardiologist identified congenital tricuspid dysplasia
      with signs of heart failure. Furosemide, enalapril, and pimobendan were used to
      reduce clinical signs and improve length and quality of life. 

PMID- 24293679
TI  - The ultimate communication challenge.

PMID- 24293680
TI  - Enantioselective Extraction System Containing Binary Chiral Selectors and
      Chromatographic Enantioseparation Method for Determination of the Absolute
      Configuration of Enantiomers of Cyclopentolate.
AB  - The distribution coefficients and enantioseparation of cyclopentolate were
      studied in an extraction system containing d-tartaric acid ditertbutyl ester in
      organic phase and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous
      phase. Various parameters involved in the enantioseparation such as the type and
      the concentration of chiral selectors, pH value and a wide range of organic
      solvents were investigated. The maximum enantioselectivity (alpha = 2.13) and
      optimum distribution coefficients (KR = 0.85, KS = 0.40) were obtained under the
      following conditions: 0.10 mol/L HP-beta-CD in aqueous phase and 0.20 mol/L d
      tartaric acid ditertbutyl ester in decanol as organic phase. Cyclopentolate is
      present as a racemic mixture to the aqueous phase. The potentially different
      biological activities of cyclopentolate enantiomers have not been examined yet.
      Two chiral liquid chromatography methods have been developed for the direct
      separation of the enantiomers of cyclopentolate. First method was used for the
      quantification analysis of cyclopentolate enantiomers in aqueous phase. Second
      method used two chiroptical detectors: electronic circular dichroism (ECD) and
      optical rotation (OR) for the identification of individual cyclopentolate
      enantiomers from the organic phase enriched with (R)-enantiomer. The absolute
      stereochemistry was determined by means of the comparison of the experimental and
      computed ECD spectra and signs of OR. The ECD spectra of chiral analytes were
      measured on-line using HPLC-ECD technique.

PMID- 24293681
TI  - Determination of Nitric Oxide-Derived Nitrite and Nitrate in Biological Samples
      by HPLC Coupled to Nitrite Oxidation.
AB  - Nitrite and nitrate are main stable products of nitric oxide, a pivotal cellular
      signaling molecule, in biological fluids. Therefore, accurate measurement of the
      two ions is profoundly important. Nitrite is difficult to be determined for a
      larger number of interferences and unstable in the presence of oxygen. In this
      paper, a simple, cost-effective and accurate HPLC method for the determination of
      nitrite and nitrate was developed. On the basis of the reaction that nitrite is
      oxidized rapidly to nitrate with the addition of acidic potassium permanganate,
      the determination of nitrite and nitrate was achieved by the following strategy:
      each sample was injected twice for HPLC analysis, i.e. the first injection was to
      measure nitrate, and the second injection was to measure total nitrate including
      initial nitrate and the nitrate from the conversion of nitrite with the addition
      of acid potassium permanganate in the sample. The amount of nitrite can be
      calculated as difference between injections 2 and 1. The HPLC separation was
      performed on a reversed phase C18 column for 15 min. The mobile phase consisted
      of methanol-water (2:98 by volume); the water in the mobile phase contained 0.60
      mM phosphate salt (potassium dihydrogen and disodium hydrogen phosphate) and 2.5
      mM tetrabutylammonium perchlorate (TBAP). The UV wavelength was set at 210 nm.
      Additionally, we systemically investigated the effects of the concentration of
      phosphate salt and TBAP in the mobile phase, the pH of the mobile phase, and the
      amount of acidic potassium permanganate added to the sample on the separation
      efficacy. The results showed that the limits of detection (LOD) and the limit of
      quantitation (LOQ) were 0.075 and 0.25 MUM for nitrate (containing the oxidized
      nitrite), respectively. The linear range was 1-800 MUM. This developed approach
      was successfully applied to assay nitrite/nitrate levels in cell culture medium,
      cell lysate, rat plasma and urine.

PMID- 24293682
TI  - Concordant female mate preferences in the cichlid fish Tropheus moorii.
AB  - Discriminating female mate preferences enhance the variance in reproductive
      success among males of a population and create a potential for sexual selection,
      which can account for trait evolution and diversification. Fish color patterns
      are among the prime targets of mate choice-driven sexual selection. Populations
      of the cichlid Tropheus from Lake Tanganyika display remarkable geographic color
      pattern variation, but the role of female choice in their rapid and rich
      phenotypic diversification is unclear. Males and females establish a pair bond
      prior to spawning monogamously, but as brood care is strictly maternal, female
      investment in reproduction is high and the operational sex ratio is male-biased.
      Therefore, variance in male reproductive success can accrue if individual males
      succeed repeatedly in securing a mate. To test this prediction in the red colored
      Tropheus moorii "Chimba", four pairs of males were presented to a series of
      females and female mate preferences were inferred from pairwise interactions.
      There was a significant difference in mating success between the males of each
      pair (P < 0.001 over all trials), as-with one exception-females shared
      preferences for the same males. Male courtship activity was strongly correlated
      with female choice. Our experiment suggests that female choice contributes to the
      variance in male reproductive success in the tested population.

PMID- 24293683
TI  - Modelling single- and tandem-bubble dynamics between two parallel plates for
      biomedical applications.
AB  - Carefully timed tandem microbubbles have been shown to produce directional and
      targeted membrane poration of individual cells in microfluidic systems, which
      could be of use in ultrasound-mediated drug and gene delivery. This study aims at
      contributing to the understanding of the mechanisms at play in such an
      interaction. The dynamics of single and tandem microbubbles between two parallel
      plates is studied numerically and analytically. Comparisons are then made between
      the numerical results and the available experimental results. Numerically,
      assuming a potential flow, a three-dimensional boundary element method (BEM) is
      used to describe complex bubble deformations, jet formation, and bubble
      splitting. Analytically, compressibility and viscous boundary layer effects along
      the channel walls, neglected in the BEM model, are considered while shape of the
      bubble is not considered. Comparisons show that energy losses modify the bubble
      dynamics when the two approaches use identical initial conditions. The initial
      conditions in the boundary element method can be adjusted to recover the bubble
      period and maximum bubble volume when in an infinite medium. Using the same
      conditions enables the method to recover the full dynamics of single and tandem
      bubbles, including large deformations and fast re-entering jet formation. This
      method can be used as a design tool for future tandem-bubble sonoporation
      experiments.

PMID- 24293684
TI  - Characteristics and consumer acceptance of healthier meat and meat product
      formulations-a review.
AB  - Awareness of health and nutrition has led to the development of "functional
      foods" which is a new approach to achieve healthier status thus reducing the risk
      of diseases. Meat has been highly exploited as a functional ingredient/food in
      recent years wherein meat has either been modified or incorporated into non meat
      products. Changing consumer demand has influenced the market for all types of
      meat. The development and marketing the functional foods can be, however, very
      challenging compared to the foods that conventionally have a high health image.
      This review gives the overall perception about importance of using meat/meat
      products as a functional food. 

PMID- 24293685
TI  - Cereal based functional food of Indian subcontinent: a review.
AB  - Due to constant health awareness and readily available information on usefulness
      of different diet and their direct link with health, the demand of functional
      food is increasing day by day. The concept of functional foods includes foods or
      food ingredients that exert a beneficial effect on host health and/or reduce the
      risk of chronic disease beyond basic nutritional functions. Increasing awareness
      of consumer health and interest in functional foods to achieve a healthy
      lifestyle has resulted in the need for food products with versatile health
      benefiting properties. Cereal- and cereal component-based food products offer
      opportunities to include probiotics, prebiotics, and fibers in the human diet.
      Various growth studies using probiotic Lactic acid bacteria on cereal-based
      substrates and utilization of whole grain or components as high-fiber foods in
      developing novel food products lend support to the idea that cereal-based media
      may well be good probiotic carriers. It is essential that science and traditional
      knowledge should go together to find mutually beneficial results. In the Indian
      subcontinent, making use of fermented food and beverages using local food crops
      and other biological resources are very common. But the nature of the products
      and the base material vary from region to region. 

PMID- 24293686
TI  - Effect of certain indigenous processing methods on the bioactive compounds of ten
      different wild type legume grains.
AB  - In recent years, research efforts are under-way on the possibilities of
      utilization of natural source of bioactive compounds for the dietary management
      of certain chronic diseases such as diabetes, obesity, cardiovascular diseases,
      cancer etc. In this connection, seed materials of promising wild type under
      utilized food legume grains such as Acacia nilotica (L.) Willd. Ex Delile,
      Bauhinia purpurea L., Canavalia ensiformis (L.) DC., Cassia hirsuta L.,
      Caesalpinia bonducella F., Erythrina indica L., Mucuna gigantea (Willd.) DC.,
      Pongamia pinnata (L.) Pierre, Sebania sesban (L.) Merr. and Xylia xylocarpa Roxb.
      Taub., collected from South India, were investigated for certain bioactive
      compounds. All the samples were found to constitute a viable source of total free
      phenolics (3.12-6.69 g/100 g DM), tannins (1.10-4.41 g/100 g DM), L-Dopa (1.34
      5.45 g/100 g DM) and phytic acid (0.98-3.14 g/100 g DM). In general, the seed
      materials of X. xylocarpa recorded high levels of total free phenolics and
      tannins, whereas the maximum levels of L-Dopa and phytic acid were noticed in M.
      gigantea and S. sesban, respectively. Further, presently investigated all the
      bioactive compounds were drastically reduced during soaking in tamarind solution
      + cooking as well as soaking in alkaline solution + cooking, and thus these
      treatments were considered to be more aggressive practices. Open-pan roasting
      also demonstrated a significant reduction of total free phenolics, tannins and
      moderate loss of L-Dopa and phytic acid. Alternatively, sprouting + oil-frying
      showed significant level of increase of total free phenolics (9-27%) and tannins
      (12-28%), but diminishing effect on phytic acid and L-Dopa. Hence, among the
      presently employed treatments, sprouting + oil-frying could be recommended as a
      suitable treatment for the versatile utilization of these wild under-utilized
      legume grains for the dietary management of certain chronic diseases. 

PMID- 24293687
TI  - Effects of preharvest treatment, disinfections, packaging and storage environment
      on quality of tomato.
AB  - The major objective of this study was to explore the significance of an
      integrated agro technology in maintenance of postharvest quality of tomato.
      Preharvest ComCat(r) treated tomatoes and untreated controls were evaluated for
      changes in physiological, chemical, and microbiological quality during storage at
      13  degrees C and room temperature (16.9-25.2  degrees C) and a relative humidity
      of 34-76%. Effects of disinfection coupled with packaging were evaluated.
      Physiological weight loss, total soluble solids, peroxidase activity and
      marketability were maintained better in anolyte disinfected tomatoes. At harvest,
      ComCat(r) treated tomatoes had lower pH, glucose and microbial populations, and
      higher total soluble solids, total titratable acids, sucrose, peroxidase activity
      than controls. The total soluble solids were better retained in ComCat(r) treated
      tomatoes than in control, while the sucrose and glucose contents remained lower
      after ripening. Peroxidase activities were lower in ripening ComCat(r) treated
      tomatoes, and difference in polygalactronase activity was only visible after 30
      days. The microbial populations were lower in ComCat(r) treated fruit.
      Marketability of ComCat(r) treated tomatoes was better than that of the control.
      Integrated technology covering preharvest ComCat(r) application, disinfection
      with anolyte water and packaging combined with cold storage at 13  degrees C
      maintained the superior quality of tomato. 

PMID- 24293688
TI  - Preparation of chitosan oligomers COS and their effect on the retrogradation of
      intermediate amylose rice starch.
AB  - Chitosan oligomers (COS) were obtained by enzymatic hydrolysis and H2O2 oxidative
      treatment, and then separated into different fractions using ultra-filtration
      membranes. Each COSM fraction prepared using enzymatic hydrolysis retained its
      structure, especially the reduced end residue (-NH2 group), and had a peak for
      molecular weight. On the other hand, each COSH fraction prepared by oxidative
      treatment had partly damaged -NH2 groups and two peaks for molecular weight.
      These results indicate that the same COS fractions prepared by the two methods
      differ in their amino groups and in their molecular weights, though they can both
      pass through the same size ultra-filtration membrane. The effect of COS on the
      retrogradation of intermediate amylose rice starch (IA-RS) was also investigated.
      The 5 k < COSM < 10 k fraction had the best anti-retrogradation ability; the
      retrogradation ratio of IA-RS with this fraction was reduced by 14.5%, compared
      to the control, and its relative crystallinity was only 59.69%. 10 k < COSM < 30
      k fraction was second best, while the COSM < 5 k fraction had no effect.
      Therefore, the molecular size of COS determined its anti-retrogradation
      capability. All COSH fractions from oxidative treatment had no effect on the
      retrogradation. 

PMID- 24293689
TI  - Effect of fat and sugar substitution on the quality characteristics of low
      calorie milk drinks.
AB  - The study was undertaken to develop low calorie functional milk drinks using
      inulin and sucralose as fat and sugar substitutes, respectively. Cardamom was
      incorporated as a flavouring ingredient. The milk fat varied from 0.5 to 1.0%,
      sugar replacement from 0 to 100%, and inulin incorporation from 0 to 8%. The
      effect on total solids (TS), total soluble solids (TSS), specific gravity,
      viscosity and sensory scores was studied. Sugar replacement considerably
      decreased TS, TSS, viscosity and sensory scores. However, increase in inulin
      significantly improved these parameters. Addition of 4% inulin was found to
      impart viscosity and sensory properties equivalent to that of control (2% fat).
      The cardamom flavoured milk drinks were prepared by replacing sugar and adding 4%
      inulin in milk of 0.5% fat and 8.5% milk solid-not-fat. The calorific value
      decreased by 43% in the experimental milk drink compared to control. 

PMID- 24293690
TI  - Effect of blends of dehydrated green pea flour and amaranth seed flour on the
      rheological, microstructure and pasta making quality.
AB  - Effect of dehydrated green pea flour (DGPF) and additives like glycerol mono
      stearate (GMS), sodium stearoyl lactylate (SSL) and dry gluten on the rheological
      characteristics and pasta making quality made from Indian Triticum aestivum was
      studied. 5-10% of amaranth seed flour was used in the formulation to enhance the
      protein and fiber contents of the product. Increase in DGPF from 0 to 30%
      decreased the maximum consistency values from 550 to 513 FU, whereas the mixing
      tolerance index values decreased from 108 to 52 FU. The cooked weight and cooking
      loss increased from 320.8 to 332.9 g% and 5.0 to 8.2% respectively and the
      firmness values decreased from 104 to 75 g. Sensory evaluation of pasta showed
      that addition of DGPF above 20% resulted in greenish colour pasta of mashy
      texture. Addition of additives improved the quality of pasta at 30% level as seen
      in the reduction in the cooking loss from 8.2 to 5.9%, increase in the firmness
      values to 140 g and improvement in the eating quality. Protein content of pasta
      improved from 9.56 to 16.57%. Scanning electron microscopic studies revealed that
      the addition of additives in combination helped in the formation of rupture free
      structure with a continuous network. 

PMID- 24293691
TI  - Effects of modified atmosphere packaging on quality of 'Alphonso' Mangoes.
AB  - Postharvest quality of Alphonso mangoes (Mangifera indica L) is vital to ensure
      proper ripening and good quality. 500 g mature green mangoes, were subjected to
      three pre- packaging hot water dips (20, 30 & 40 degrees C) for 40 min, two
      packaging films (OPP unperforated and perforated), using three levels of gas
      concentrations of 25,50 and 75% v/v CO2 treatments (balance N2) and stored at 10
      degrees C for 21 days. During the storage period headspace gas composition,
      weight loss, ascorbic acid, pulp firmness, external fruit colour and overall
      quality score were measured to determine optimum storage conditions. The most
      effective postharvest condition was found to be dipping in water maintained at 40
      degrees C for 40 min, followed by packaging under 50% CO2 in bags made of
      unperforated film when compared to mangoes packed under 25 and 75% CO2 which
      showed deteriorated quality including spoilage and mould. Good keeping quality of
      at least 21 days was achieved under these conditions, which was much superior to
      the control samples that showed deterioration after 12 days of storage. 

PMID- 24293692
TI  - Characterization of the antioxidant properties of phenolic extracts from some
      citrus peels.
AB  - This study sought to determine the distribution of free and bound phenolics in
      some Nigerian citrus peels [orange (Citrus sinensis), grapefruit (Citrus
      paradisii) and shaddock (Citrus maxima)] and characterize the antioxidant
      properties. The free phenolics were extracted with 80% acetone, while the bound
      phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl
      acetate. Free phenolic extracts had significantly higher (P < 0.05) DPPH*
      scavenging ability than the bound phenolic extracts, except in orange peels where
      the bound phenolic extracts had significantly higher (P < 0.05) DPPH* scavenging
      ability. Bound phenolics from orange peels had the highest ABTS* scavenging
      ability (6.09 mmol./TEAC g) and ferric reducing antioxidant properties (FRAP)
      (71.99 mg/GAE 100 g), while bound phenolics from shaddock peels had the least
      ABTS* scavenging ability (1.35 mmol./TEAC g) and FRAP (2.58 mg/GAE 100 g) . Bound
      phenolics from grapefruit peels had the highest OH* scavenging ability (EC50 =
      3.8 mg/ml), while bound phenolics from shaddock peels had the least (EC50 = 16.1
      mg/ml). The phenolics chelated Fe(2+) and inhibited malondialdehyde production in
      rat's pancreas in a dose-dependent manner. The additive and/or synergistic action
      of the free and bound phenolics could have contributed to the observed medicinal
      properties of the peels; therefore, the high antioxidant properties of the free
      and bound phenolic extracts from orange peels could be harness in the formulation
      of nutraceuticals and food preservatives. 

PMID- 24293693
TI  - Effect of multiple fortification on the bioavailability of minerals in wheat meal
      bread.
AB  - Bioavailability of calcium, iron and zinc as calcium carbonate (CaCO3), ferrous
      sulfate (FeSO4) and zinc sulphate (ZnSO4) @ 1,000, 40 and 20 mg kg(-1)
      respectively from fortified bread of 72% extraction straight grade flour was
      assessed. Fortified bread diets were fed to 64 female Sprague-Dawley Albino rats
      for a period of 28 days. The retention of Ca, Fe and Zn was measured in plasma,
      femur and liver tissues of rats. The results showed that the feed intake and live
      body weight of the experimental animals increased significantly with the time
      period. The Ca levels in plasma and liver did not change significantly while in
      femur, Ca retention changed significantly with changing type of the fortificants.
      Similarly, the results for percent apparent absorption (AA) of Ca also remained
      unchanged (P < 0.05). The Fe and Zn levels were significantly higher in the
      plasma, liver and femur of rats fed Fe and Zn fortified bread. Interaction of Ca,
      Fe and Zn resulted in their decreased bioavailability. However Ca, Fe and Zn
      absorption was higher in the rats fed triple fortified diet compared with those
      fed unfortified bread diet. This negative interaction did not appear to be great
      enough to discourage multiple fortification of flour to address minerals
      malnutrition in the vulnerable groups. 

PMID- 24293694
TI  - Fermentation of xylo-oligosaccharides obtained from wheat bran and Bengal gram
      husk by lactic acid bacteria and bifidobacteria.
AB  - Different strains of Bifidobacteria, Lactobacilli and Pediococci spp. were
      evaluated for their utilization of xylo-oligosaccharides derived from Bengal gram
      husk and wheat bran water extractable polysaccharides. The fermentation pattern
      of xylo-oligosaccharides by bacteria depends on the nature of xylo
      oligosaccharides i.e. degree of polymerization and arabinose to xylose ratio as
      well as the bacterial strain tested, which inturn are very important for
      designing species-specific prebiotic xylo-oligosaccharides and synbiotic
      preparations for incorporation in various health foods. All the bacterial strains
      tested readily utilized xylo-oligosaccharides derived from bengal gram husk and
      wheat bran as indicated by the increase in (a) turbidity of the culture broth (b)
      xylanase, xylosidase and arabinosidase activities (c) dry cell mass and (d) the
      liberation of short chain fatty acids (SCFA). Acetate was found to be the major
      SCFA produced as the end product of fermentation and its amount varied from 75.4
      to 100 mol%. Xylo-oligosaccharides derived from wheat bran were found to have
      better prebiotic activity compared to the one derived from Bengal gram husk and
      this can be ascribed to relatively high amount of arabinose. 

PMID- 24293695
TI  - Effect of skin coatings on prolonging shelf life of kagzi lime fruits (Citrus
      aurantifolia Swingle).
AB  - An experiment was conducted to assess the influence of chemical and oil coatings
      on storage life of kagzi lime fruits. Fruits were harvested at physiological
      light green mature stage and treated with different concentrations of chemicals
      viz., Cacl2 and KMnO4 and edible coatings viz., (coconut oil, mustard oil,
      sesamum oil, castor oil and liquid paraffin wax). After treatment, fruits were
      kept at ambient condition (25-30  degrees C, 60-70% RH) till 18 days and analyzed
      for various physical and chemical parameters like PLW, marketable fruits
      retained, TSS, acidity, ascorbic acid, juice content and also organoleptic
      values. The results revealed that edible oil emulsion coating particularly
      coconut oil had significantly (p <= 0.05) effect on reduction of the
      physiological loss in weight (9.67%) and maximum marketable fruits retained
      (70%), total soluble solids (8.43%), ascorbic acid (49.93 mg/100 ml juice),
      acidity (1.52%) and juice content (42.34%) of fruits. Similarly, application of
      this oil emulsion coating acceptable for sensory quality parameters such as
      appearance, flavour, taste, external colour and no incidence of moulds & their
      growth up to 18 days of storage. 

PMID- 24293696
TI  - Infrared drying of sweet potato (Ipomoea batatas L.) slices.
AB  - The effect of different infrared power levels (104, 125, 146 and 167 W) on drying
      kinetics and rehydration ratio of sweet potato slices was investigated. It was
      observed that the power levels affected the drying time and rehydration ratio.
      The increase in infrared power level decreased the drying time. The experimental
      data obtained from drying study were fitted with Newton, Henderson and Pabis and
      Logarithmic models to evaluate the drying kinetics of the sweet potato slices.
      The fit quality of the proposed models was evaluated by using the determination
      of coefficient (R (2) ), mean relative percent error (P), reduced chi-square (chi
      (2) ) and root means square error (RMSE). Among the three drying models, the
      Logarithmic model gave a better fit over the other two models. Effective
      diffusivity varied from 1.31 * 10(-10) to 3.66 * 10(-10) m(2)/s and was
      significantly influenced by infrared power. 

PMID- 24293697
TI  - Fibres as an additive for oil reduction in deep fat fried poori.
AB  - Models capable of predicting the moisture and oil content as well as overall
      acceptability (OAA) of poori, prepared from wheat flour incorporated with wheat
      bran and oat bran were developed using response surface methodology. Central
      composite rotatable design with two independent variables (wheat bran and oat
      bran) at five levels (wheat bran, 3-9 g/100 g wheat flour and oat bran 6-12 g/100
      g wheat flour) was used to optimize the bran level. Results showed that oat bran
      had significant (p <= 0.05) positive effect on moisture retention and negative
      effect on oil absorption, while wheat bran had reverse effect. Based on
      compromise optimization, it was recommended to incorporate 3.0 g wheat bran and
      11.0 g oat bran (per 100 g wheat flour) for making fibre rich (4.2% total dietary
      fibre, 1.3% soluble dietary fibre) poori with lower oil content (20% less as
      control) and optimum acceptability (88.6). 

PMID- 24293698
TI  - Evaluation of the proximate, fatty acid and mineral composition of representative
      green, brown and red seaweeds from the Persian Gulf of Iran as potential food and
      feed resources.
AB  - The proximate, fatty acid and mineral composition were determined for green (Ulva
      lactuca and Enteromorpha intestinalis), brown (Sargassum ilicifolium and
      Colpomenia sinuosa) and red (Hypnea valentiae and Gracilaria corticata) seaweeds
      collected from the Persian Gulf of Iran. Results showed that the seaweeds were
      high in carbohydrate (31.8-59.1%, dry weight) and ash (12.4-29.9%) but low in
      lipid content (1.5-3.6%). The protein content of red or green seaweeds was
      significantly higher (p < 0.05) compared to brown seaweeds. The fatty acid
      composition of various seaweed lipids varied considerably with 51.9-67.4% of
      saturates, 22.0-32.9% of monoenes and 9.2-19.1% of polyunsaturated fatty acids
      (PUFA). E. intestinalis contained the highest total n-3 PUFA content with the
      lowest n-6/n-3 ratio. Persian Gulf seaweeds contained higher concentrations of
      all the minerals examined (K, Mg, Fe, Mn, Cu, Zn and Co) compared to terrestrial
      vegetables. Seaweeds could potentially be used as a food or feed additive in
      Iran. 

PMID- 24293699
TI  - Comparative antioxidant effect of aqueous extracts of curry leaves, fenugreek
      leaves and butylated hydroxytoluene in raw chicken patties.
AB  - Antioxidant properties and use of aqueous extracts of curry leaves (Murraya
      koenigii) and fenugreek leaves (Trigonella foenum-graecum) as source of natural
      antioxidant in raw chicken meat were evaluated. Four treatments viz., I. Control
      (meat +2% salt), II.BHT (meat +2% salt +0.1% BHT), III. CLE (meat +2% salt +2%
      curry leaves extract) and IV. FLE (meat +2% salt +2% fenugreek leaves extract)
      were compared for lipid oxidation during eight days refrigerated storage. The
      average phenolic content was 59.2 and 52.8 mg/g gallic acid equivalent in CLE and
      FLE respectively. Free radical scavenging activity was 61.4 and 64.2% in CLE and
      FLE, respectively. CLE had significantly (P < 0.05) higher reducing activity
      (2.4) as compared to FLE (2.2). Observation on lipid oxidation showed a
      significant (p < 0.05) higher TBARS values in control patties than other patties
      containing BHT, CLE and FLE. Overall percent increase during storage period was
      highest in control followed by BHT, CLE and FLE. Both synthetic antioxidants and
      natural extracts significantly (p < 0.05) decreased the TBARS values. The average
      percent decrease in TBARS values during storage was 18, 25.5 and 27.5 in BHT, CLE
      and FLE treatments, respectively. Therefore, it was concluded that water extracts
      obtained from curry leaves and fenugreek leaves could be explored as natural
      antioxidants in poultry meat and meat products. 

PMID- 24293700
TI  - Quality characteristics of bread produced from wheat, rice and maize flours.
AB  - Rice (Oryza sativa) flour and maize (Zea mays) meal substitution in wheat
      (Triticum aestivum) flour, from 0 to 100% each, for the production of bread was
      investigated. The proximate analysis, pasting properties, bread making qualities
      of raw materials and sensory evaluation of the bread samples were determined. The
      pasting temperature increased with increased percentage of rice flour and maize
      meal. But the other pasting characters decreased with the higher proportion of
      rice flour. The baking absorption was observed to increase with higher level of
      maize meal but it decreased when level of rice flour was increased. Loaf weight
      (g) decreased with progressive increase in the proportion of maize meal but
      increased when rice flour incorporation was increased. Loaf volume, loaf height
      and specific volume decreased for progressively higher level of maize meal and
      rice flour. The sensory evaluation revealed that 25% replacement of wheat flour
      was found to be more acceptable than control sample. 

PMID- 24293701
TI  - From Statistics to Diagnostics: Medical Certificates, Melancholia, and "Suicidal
      Propensities" in Victorian Psychiatry.

PMID- 24293702
TI  - Surface-initiated Polymerization of Azidopropyl Methacrylate and its Film
      Elaboration via Click Chemistry.
AB  - Azidopropyl methacrylate (AzPMA), a functional monomer with a pendent azido
      group, polymerizes from surfaces and provides polymer brushes amenable to
      subsequent elaboration via click chemistry. In DMF at 50  degrees C, click
      reactions between poly(AzPMA) brushes and an alkynylated dye proceed with >90%
      conversion in a few minutes. However, in aqueous solutions, reaction with an
      alkyne-containing poly(ethylene glycol) methyl ether (mPEG, Mn=5000) gives <10%
      conversion after a 12-h reaction at room temperature. Formation of copolymers
      with AzPMA and polyethylene glycol methyl ether methacrylate (mPEGMA) enables
      control over the hydrophilicity and functional group density in the copolymer to
      increase the yield of aqueous click reactions. The copolymers show reaction
      efficiencies as high as 60%. These studies suggest that for aqueous applications
      such as bioconjugation via click chemistry, control over brush hydrophilicity is
      vital.

PMID- 24293703
TI  - Urban Vegetation Cover and Vegetation Change in Accra, Ghana: Connection to
      Housing Quality.
AB  - The objectives are to (1) quantify, map, and analyze vegetation cover
      distributions and changes across Accra, Ghana, for 2002 and 2010; and (2) examine
      the statistical relationship between vegetation cover and a housing quality index
      (HQI) for 2000 at the neighborhood level. Pixel-level vegetation cover maps
      derived using threshold classification of 2002 and 2010 QuickBird normalized
      difference vegetation index images have very high overall accuracies and yield an
      estimate of 5.9 percent vegetation cover reduction over the study area between
      2002 and 2010. A high degree of variance in vegetation cover for individual dates
      is explained by HQI at the neighborhood level, although minimal covariability
      between absolute or relative vegetation cover change and HQI for 2000 was
      observed.

PMID- 24293704
TI  - India's Latent Foe: Multi Drug Resistant Tuberculosis.

PMID- 24293705
TI  - Trichoderma-plant-pathogen interactions: advances in genetics of biological
      control.
AB  - Trichoderma spp. are widely used in agriculture as biofungicides. Induction of
      plant defense and mycoparasitism (killing of one fungus by another) are
      considered to be the most important mechanisms of Trichoderma-mediated biological
      control. Understanding these mechanisms at the molecular level would help in
      developing strains with superior biocontrol properties. In this article, we
      review our current understanding of the genetics of interactions of Trichoderma
      with plants and plant pathogens. 

PMID- 24293707
TI  - Mining the metagenome of activated biomass of an industrial wastewater treatment
      plant by a novel method.
AB  - Metagenomic libraries herald the era of magnifying the microbial world, tapping
      into the vast metabolic potential of uncultivated microbes, and enhancing the
      rate of discovery of novel genes and pathways. In this paper, we describe a
      method that facilitates the extraction of metagenomic DNA from activated sludge
      of an industrial wastewater treatment plant and its use in mining the metagenome
      via library construction. The efficiency of this method was demonstrated by the
      large representation of the bacterial genome in the constructed metagenomic
      libraries and by the functional clones obtained. The BAC library represented 95.6
      times the bacterial genome, while, the pUC library represented 41.7 times the
      bacterial genome. Twelve clones in the BAC library demonstrated lipolytic
      activity, while four clones demonstrated dioxygenase activity. Four clones in pUC
      library tested positive for cellulase activity. This method, using FTA cards, not
      only can be used for library construction, but can also store the metagenome at
      room temperature. 

PMID- 24293706
TI  - Acquired resistance to macrolide-lincosamide-streptogramin antibiotics in lactic
      Acid bacteria of food origin.
AB  - Antibiotic resistance is a growing problem in clinical settings as well as in
      food industry. Lactic acid bacteria (LAB) commercially used as starter cultures
      and probiotic supplements are considered as reservoirs of several antibiotic
      resistance genes. Macrolide-lincosamide-streptogramin (MLS) antibiotics have a
      proven record of excellence in clinical settings. However, the intensive use of
      tylosin, lincomysin and virginamycin antibiotics of this group as growth
      promoters in animal husbandry and poultry has resulted in development of
      resistance in LAB of animal origin. Among the three different mechanisms of MLS
      resistance, the most commonly observed in LAB are the methylase and efflux
      mediated resistance. This review summarizes the updated information on MLS
      resistance genes detected and how resistance to these antibiotics poses a threat
      when present in food grade LAB. 

PMID- 24293708
TI  - Assessment of Microbial Richness in Pelagic Sediment of Andaman Sea by Bacterial
      Tag Encoded FLX Titanium Amplicon Pyrosequencing (bTEFAP).
AB  - Microbial diversity of 1,000 m deep pelagic sediment from off Coast of Andaman
      Sea was analyzed by a culture independent technique, bacterial tag encoded FLX
      titanium amplicon pyrosequencing. The hypervariable region of small subunit
      ribosomal rRNA gene covering V6-V9, was amplified from the metagenomic DNA and
      sequenced. We obtained 19,271 reads, of which 18,206 high quality sequences were
      subjected to diversity analysis. A total of 305 operational taxonomic units
      (OTUs) were obtained corresponding to the members of firmicutes, proteobacteria,
      plantomycetes, actinobacteria, chloroflexi, bacteroidetes, and verucomicrobium.
      Firmicutes was the predominant phylum, which was largely represented with the
      family bacillaceae. More than 44 % of sequence reads could not be classified up
      to the species level and more than 14 % of the reads could not be assigned to any
      genus. Thus, the data indicates the possibility for the presence of uncultivable
      or unidentified novel bacterial species. In addition, the community structure
      identified in this study significantly differs with other reports from marine
      sediments. 

PMID- 24293709
TI  - Mycotoxin-producing ability and chemotype diversity of Aspergillus section flavi
      from soils of peanut-growing regions in iran.
AB  - Invasion of crops with Aspergillus flavus may result in contamination of food and
      feed with carcinogenic mycotoxins such as aflatoxins (AF) and cyclopiazonic acid
      (CPA). In the present study, distribution and toxigenicity of Aspergillus flavus
      and A. parasiticus in soils of five peanut fields located in Guilan province,
      Northern Iran was investigated. From a total of 30 soil samples, 53 strains were
      isolated which all of them were finally identified as A. flavus by a combination
      of colony morphology, microscopic criteria and mycotoxin profiles.
      Chromatographic analysis of fungal cultures on yeast extract sucrose broth by tip
      culture method showed that 45 of the 53 A. flavus isolates (84.9 %) were able to
      produce either CPA or AFB1, while eight of the isolates (15.1 %) were non
      toxigenic. The amounts of CPA and AFB1 produced by the isolates were reported in
      the range of 18.2-403.8 MUg/g and 53.3-7446.3 MUg/g fungal dry weights,
      respectively. Chemotype classification of A. flavus isolates based on the ability
      for producing mycotoxins and sclerotia showed that 43.4 % were producers of CPA,
      AFB1 and sclerotia (group I), 13.2 % of CPA and AFB1 (group II), 9.4 % of AFB1
      and sclerotia (group III), 13.2 % of AFB1 (group IV), 5.7 % of CPA and sclerotia
      (group V) and 15.1 % were non-toxigenic with no sclerotia (group VI). No strain
      was found as producer of only CPA or sclerotia. These results indicate different
      populations of mycotoxigenic A. flavus strains enable to produce hazardous
      amounts of AFB1 and CPA are present in peanuts field soils which can be quite
      important regard to their potential to contaminate peanuts as a main crop
      consumed in human and animal nutrition. 

PMID- 24293710
TI  - High Prevalence and Significant Association of ESBL and QNR Genes in Pathogenic
      Klebsiella pneumoniae Isolates of Patients from Kolkata, India.
AB  - Pathogenic Klebsiella pneumoniae, resistant to beta-lactam and quinolone drugs,
      is widely recognized as important bacteria causing array of diseases. The
      resistance property is obtained by acquisition of plasmid encoded blaTEM, blaSHV,
      blaCTX-M, QNRA, QNRB and QNRS genes. The aim of this study was to document the
      prevalence and association of these resistant genes in K. pneumoniae infecting
      patients in India. Approximately 97 and 76.7 % of the 73 K. pneumoniae isolates
      showed resistance towards beta-lactam and quinolone drugs respectively. Bla genes
      were detected in 74 % of K. pneumoniae isolates; with prevalence in the following
      order: blaTEM > blaSHV > blaCTXM. QNR genes were detected in 67 % samples. Chi
      square analysis revealed significant association between presence of bla and qnr
      genes in our study (P value = 0.000125). Sequence analysis of some blaTEM,
      blaSHV, blaCTX-M and QNRB PCR products revealed presence of blaTEM1 (GenBank
      accession: JN193522), blaTEM116 (JN193523 and JN193524), blaSHV11, blaCTXM72
      variants (JF523199) and QNRB1 (JN193526 and JN193527) in our samples. 

PMID- 24293711
TI  - A New Species and Genus Distribution Record from China: Neoscytalidium
      novaehollandiae.
AB  - One isolate from bark beetle galleries was identified and characterized using
      morphological and molecular methodology, and described and illustrated based on
      these data. These results identified a new species distribution record in China
      for Neoscytalidium novaehollandiae. Species morphology and micrographs are
      provided in this paper. The specimens are stored in Northeast Forestry
      University. 

PMID- 24293712
TI  - Genetic Variability of Beauveria bassiana and a DNA Marker for Environmental
      Monitoring of a Highly Virulent Isolate Against Cosmopolites sordidus.
AB  - The banana weevil Cosmopolites sordidus (Germar) is one of a number of pests that
      attack banana crops. The use of the entomopathogenic fungus Beauveria bassiana as
      a biological control agent for this pest may contribute towards reducing the
      application of chemical insecticides on banana crops. In this study, the genetic
      variability of a collection of Brazilian isolates of B. bassiana was evaluated.
      Samples were obtained from various geographic regions of Brazil, and from
      different hosts of the Curculionidae family. Based on the DNA fingerprints
      generated by RAPD and AFLP, we found that 92 and 88 % of the loci were
      polymorphic, respectively. The B. bassiana isolates were attributed to two
      genotypic clusters based on the RAPD data, and to three genotypic clusters, when
      analyzed with AFLP. The nucleotide sequences of nuclear ribosomal DNA intergenic
      spacers confirmed that all isolates are in fact B. bassiana. Analysis of
      molecular variance showed that variability among the isolates was not correlated
      with geographic origin or hosts. A RAPD-specific marker for isolate CG 1024,
      which is highly virulent to C. sordidus, was cloned and sequenced. Based on the
      sequences obtained, specific PCR primers BbasCG1024F (5'-TGC GGC TGA GGA GGA CT
      3') and BbasCG1024R (5'-TGC GGC TGA GTG TAG AAC-3') were designed for detecting
      and monitoring this isolate in the field. 

PMID- 24293713
TI  - Altered Transcriptome of the B. melitensis Vaccine Candidate 16MDeltavjbR,
      Implications for Development of Genetically Marked Live Vaccine.
AB  - The VjbR protein induced antibody responses in both human and animal brucellosis,
      and the vjbR mutant 16MDeltavjbR is an ideal vaccine candidate because of the
      feasibility of using the VjbR as diagnostic antigen. To further characterize this
      vaccine candidate and provide information for vaccine development, in the present
      study, a whole genome DNA microarray of 16M were used to compare the
      transcriptome of the vjbR mutant to that of the wild type strains. A total of 126
      genes were greatly differentially expressed in the vjbR mutant. A great
      proportion of virB and flagellar genes were differentially expressed in the vjbR
      mutant, implying that the vjbR regulate expression of virulence genes by sensing
      intracellular environments. Interestingly, the virB genes are regulated by the
      vjbR in independent manners as shown by their different fold changes and
      transcription abundances. A number of genes involved in translation, stress
      response, amino acid transport and metabolism, cell wall/membrane biogenesis,
      energy production and conversion, translation were differentially expressed. The
      vjbR mutant showed increased sensitivity to stresses of nutrition limitation,
      oxidative stress and acidification, and decreased survival in macrophage and
      mice, being consistent with its transcription profiles. These results indicated
      that the quorum sensing regulator vjbR could sense intracellular environments and
      response to them by regulate expression of virulence genes and other
      intracellular survival related genes, and therefore contribute to Brucella
      survival in host cells. This also provided direct evidence for the rational
      vaccine design by using antigenic global regulator for future development of
      genetically marked vaccine for brucellosis. 

PMID- 24293714
TI  - Detection of Quorum Sensing Signal Molecules in Edwardsiella ictaluri Ei-151.
AB  - Edwardsiella ictaluri is a Gram-negative pathogenic bacterium in the family
      Enterobacteriaceae that causes enteric septicemia of catfish, which has become a
      significant problem in the aquaculture of striped catfish (Pangasianodon
      hypophthalmus) in Vietnam. In this study, a bacterium designated as Ei-151 was
      isolated from diseased striped catfish and proved to be virulent. Based on 16S
      rDNA sequencing and phenotypic tests, the pathogenic bacterium was identified as
      Edw. ictaluri. The presence of quorum sensing signal molecules in Edw. ictaluri
      Ei-151 was detected with different biosensor strains. The results showed that Ei
      151 produced at least three kinds of acylated homoserine lactone (AHL) signal
      molecules as detected with the biosensor Agrobacterium tumefaciens KYC55, and the
      AHLs fingerprint was similar to that of Edw. tarda. During its entire growth, the
      levels of AHLs and autoinducer-2 produced by Ei-151 peaked at the stationary
      phase (OD600 1.8), which suggested that both of them may function at the
      stationary phase. No Cholerae autoinducer-1-like activity (including Edw.
      ictaluri LMG7860(T)) was detected. 

PMID- 24293715
TI  - Putative Virulence Genes and Biofilm Production Among Typical Enteroaggregative
      Escherichia coli Isolates from Diarrhoeic Children in Kashmir and Andhra Pradesh.
AB  - Fifty-eight typical EAEC isolates from children with diarrhoea were examined for
      HEp-2 cell adherence assay, presence of dispersin (aap), yersiniabactin (irp2),
      plasmid encoded toxins (pet), Shigella enterotoxin1 (set1A) and cryptic open
      reading frame (shf) putative virulence genes by polymerase chain reaction as well
      as for biofilm production. All the isolates showed aggregative adherence pattern
      on HEp-2 cells. All but five isolates (91.3 %) carried aap gene. While irp2, pet,
      set1A and shf genes were detected in 68.9, 5.1, 39.6, and 60.3 % isolates,
      respectively. Thirty-three (64.7 %) isolates out of 51 tested were found to
      produce biofilm which was found to be significantly associated only with set1A
      virulence gene (P = 0.025). Highest amount of biofilm was produced by a strain
      that possessed all the genes studied. Out of 14 isolates in which the most
      frequent gene combination (aap, irp2 and shf) was observed, only six produced
      biofilm. It is concluded that there is significant heterogeneity in putative
      virulence genes of EAEC isolates from diarrhoeic children and biofilm formation
      is associated with multiple genes. 

PMID- 24293716
TI  - Characterisation of the Virulence Factors and Genetic Types of Methicillin
      Susceptible Staphylococcus aureus from Patients and Healthy Individuals.
AB  - Methicillin sensitive Staphylococcus aureus is an important bacterial pathogen
      associated with hospital- and community-acquired infections leading to
      endocarditis, skin tissue infection and pneumonia. The objective of this study
      was to determine both the genetic characteristics of methicillin-sensitive S.
      aureus (MSSA) strains, and the occurrence of virulence factors produced by S.
      aureus strains isolated from UMMC and healthy students in the University from
      year 2009. Out of 429 nasal swab samples, 67 were MSSA. The prevalence of 21
      different virulence genes among 67 Malaysian clinical and community MSSA strains
      was determined by PCR, and their genetic features were assessed by PCR-RFLP of
      coa gene, agr types, spa typing and PFGE. The five predominant virulence genes
      were ica (79 %), efb and fnbA (61 % each), sdrE (57 %) and hlg (45 %). Toxin
      genes (enterotoxin, etd and pvl) were significantly more common (P < 0.05) in
      clinical strains compared to community strains. Three agr genotypes were
      observed: agr type I (45 %), agr type III (25 %) and agr type II (19 %). All 67
      MSSA strains were distinguished into 26 profiles by PCR-RFLP of coa, 55
      pulsotypes and 21 spa types. Four novel spa types (t7312, t7581, t7582 and t7583)
      were observed. In conclusion, different virulence profiles were observed in MSSA
      strains in Malaysia where toxin genes were more prevalent among clinical strains.
      No correlation between DNA profiles (coa-RFLP, PFGE and spa) and virulotypes was
      observed. The Malaysian MSSA strains from clinical and community sources were
      genetically diverse and heterogeneous. 

PMID- 24293717
TI  - Antimicrobial Activity of Artemisia absinthium Against Surgical Wounds Infected
      by Staphylococcus aureus in a Rat Model.
AB  - The wound infection is one of the frequent complications in patients undergoing
      surgical operations. Staphylococcus aureus is the most common cause of surgical
      wounds. Artemisia absinthium has been shown to bear strong antimicrobial
      activity, especially against Gram-positive pathogens. This study was designed to
      investigate the antimicrobial effects of A. absinthium against surgical wounds
      infected by S. aureus in a rat model. Twenty male Sprague-Dawley rats were
      divided randomly into two equal groups of treated and control rats. A circular
      incision was created on the dorsal inter-scapular region of each rat. After skin
      wounding, rats were inoculated locally with 1 * 10(4) CFU of S. aureus at sites
      of skin wounds. The extract was applied topically twice a day throughout the
      experiment. Animals of the control group were left untreated. Results have
      revealed that topical application of A. absinthium extract on the infected wound
      sites produced significant antibacterial activity against S. aureus. 

PMID- 24293718
TI  - Streptomyces antibioticalis, a Novel Species from a Sanitary Landfill Soil.
AB  - A novel isolate belonging to the genus Streptomyces, strain SL-4(T), was isolated
      from soil sample collected from a sanitary landfill, New Delhi, India. The
      taxonomic status of this isolate was studied by polyphasic approach including
      morphological, physiological and chemo-taxonomic characterization. Spore chains
      of SL-4(T) were open loops, hooks or extended spirals of wide diameter
      (retinaculiperti). The cell wall peptidoglycan of the isolate SL-4(T) contained
      L,L-diaminopimelic acid, suggesting that the strain has a cell wall of chemotype
      I. The polar lipid profile of the isolate was of Type II, with
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and
      phosphatidylinositol mannosides. The 16SrRNA gene sequence similarity between SL
      4(T) and its phylogenetic relatives Streptomyces atrovirens NRRLB 16357 (T)
      (DQ026672), S. albogriseolus NRRLB 1305 (T) (AJ494865), S viridodiastaticus NBRC
      13106 (T) (AB184317), S. caelestis NRRL 2418 (T) (X80824), S. flavoviridis NBRC
      12772 (T) (AB184842), S. pilosus NBRC 12807 (T) (AB184161) and S. longispororuber
      NBRC 13488 (T) (AB184440) was 99.65, 99.65, 99.64, 99.23, 99.15, 99.14 and 99.13
      % respectively. Subsequent DNA-DNA hybridization experiments with the test strain
      and its clade members showed 55.27, 44.27, 36.86, and 15.65 % relatedness between
      SL-4(T) and its relatives S. atrovirens, S. albogriseolus, S. viridodiastaticus
      and S. longispororuber respectively. The genotypic and phenotypic data was
      analyzed to verify possibility of the isolate SL-4(T) representing novel member
      of the genus Streptomyces, for which the name S. antibioticalis is being
      proposed. The type strain is SL-4(T) (=CCM 7434(T)=MTCC 8588(T)). 

PMID- 24293719
TI  - Frequency of ace, epa and elrA Genes in Clinical and Environmental Strains of
      Enterococcus faecalis.
AB  - Surface proteins play an important role in the pathogenesis of enterococcal
      infections. Some of them are candidates for a vaccine, e.g., the frequency of
      endocarditis in rats vaccinated with Ace protein was 75 % as 12 opposed to 100 %
      in those who weren't. However, there are other components of enterococcal cells,
      such as Epa antigens or internalin-like proteins, which may be used in the
      prophylaxis of infections caused by them. However, also other virulence factors
      and resistance to antibiotics are important during enterococcal infection.
      Therefore, the relevance of ace, epa, elrA, other virulence genes, as well as
      resistance to antibiotics was investigated. 161 Enterococcus faecalis strains
      isolated from teaching hospitals in Lodz, cultured according to standard
      microbiological methods, were investigated for the presence of genes encoding
      surface proteins by PCR. Results were analyzed with chi(2) test. The elrA gene
      was found in all clinical and environmental strains, the ace gene was also
      widespread among E. faecalis (96.9 %). Both tested epa genes were found in the
      majority of isolates (83.25 %). There was correlation between the presence of esp
      and ace genes (p = 0.046) as well as between epa and agg genes (p = 0.0094;
      chi(2) test). The presence of the genes encoding surface proteins investigated in
      our study in the great majority of isolates implies that they would appear to be
      required during E. faecalis infection. Therefore, they could be excellent targets
      in therapy of enterococcal infections or, as some studies show, candidates for
      vaccines. 

PMID- 24293720
TI  - Isolation and Characterization of Antibacterial Compound from a Mangrove
      Endophytic Fungus, Penicillium chrysogenum MTCC 5108.
AB  - Microorganisms, especially endophytic fungi that reside in the tissue of living
      mangrove plants, seem to play a major role in meeting the general demand for new
      biologically active substances. During the course of screening for biologically
      active secondary metabolites from marine microorganisms, an antibiotic compound
      containing an indole and a diketopiperazine moiety was isolated from the culture
      medium of Penicillium chrysogenum, (MTCC 5108), an endophytic fungus on the
      mangrove plant Porteresia coarctata (Roxb.). The cell free culture medium of P.
      chrysogenum showed significant activity against Vibrio cholerae, (MCM B-322), a
      pathogen causing cholera in humans. Bioassay guided chemical characterization of
      the crude extract led to the isolation of a secondary metabolite possessing a
      molecular formula C19H21O2N3. Its antibacterial activity was comparable with
      standard antibiotic, streptomycin. This compound (1) was found to be (3,1'
      didehydro-3[2"(3'",3'"-dimethyl-prop-2-enyl)-3"-indolylmethylene]-6-methyl pipera
      zine-2,5-dione) on the basis of mass spectrometry, infrared spectroscopy and one
      and two-dimensional nuclear magnetic resonance analysis. 

PMID- 24293721
TI  - Isolation and Characterization of Antidermatophytic Bioactive Molecules from
      Piper longum L. Leaves.
AB  - Piper longum L. (Piperaceae) commonly known as "long pepper" is a well known
      medicinal plant in ayurveda. Different parts of this plant, such as root, seed,
      fruit, whole plant etc. are used traditionally in various ailments. Here we have
      investigated the antidermatophytic activity of sequentially extracted petroleum
      ether, chloroform, methanol and water extracts from P. longum leaf against
      Trichophyton mentagrophytes, T. rubrum, T. tonsurans, Microsporum fulvum and M.
      gypseum. Better activity of chloroform and methanol extracts was observed. The
      chloroform extract was selected for further study and the MIC value was recorded
      as 5.0 mg ml(-1) against the test organisms. In the chloroform extract, tannins
      and phenolic compounds were detected. Further activity-guided fractionation of
      chloroform extract by silica gel column chromatography yielded nine major
      fractions. Among these, fraction-1, 4, 5 and 7 showed higher antidermatophytic
      activity. Fraction-4 on further purification by repeated column chromatography
      yielded a potential antidermatophytic fraction showing MIC value of 0.625 mg ml(
      1) against T. mentagrophytes and T. rubrum as determined by broth microdilution
      method. The major compounds were identified as 1,2-benzenedicarboxylic acid,
      bis(2-ethylhexyl) ester (C24H38O4] (41.45 %), 2,2-dimethoxybutane (C6H14O2] (13.6
      %) and beta-myrcene (C10H16) (6.75 %) based on GC-MS data. 

PMID- 24293722
TI  - Molecular Cloning and Nucleotide Sequence of the Gene for an Alkaline Protease
      from Bacillus circulans MTCC 7906.
AB  - Bacillus circulans MTCC 7906, an extracellular alkaline protease producer was
      genetically characterized. B. circulans genomic DNA was isolated, oligonucleotide
      primers specific to alkaline protease gene of B. circulans were designed and its
      PCR amplification was done. The purified PCR product and pTrcHisA vector were
      subjected to restriction digestion with NcoI and HindIII and transformed into
      Escherichia coli DH5-alpha competent cells. The recombinant expression of
      alkaline protease gene studied by inducible expression and analysis by SDS-PAGE,
      established that the alkaline protease protein had an estimated molecular size of
      46 kDa. Gene sequencing of the insert from selected recombinant clone showed it
      to be a 1329 bp gene encoding a protein of 442 amino acids. The sequence was
      blasted and aligned with known alkaline protease genes for comparison with their
      nucleotide and amino acid sequences. This identified major matches with three
      closely related subsp. of B. subtilis (B. subtilis subsp. subtilis strain 168, B.
      subtilis BSn5 and B. subtilis subsp. spizizenii strain W23). The insert also
      showed a number of substitutions (mutations) with other sp. of Bacillus which
      established that alkaline protease of B. circulans MTCC 7906 is a novel gene. The
      phylogenetic analysis of alkaline protease gene and its predicted amino acid
      sequences also validated that alkaline protease gene is a novel gene and the same
      has been accessioned in GenBank with accession number JN645176.1. 

PMID- 24293723
TI  - Antibacterial Efficacy of Dihydroxylated Chalcones in Binary and Ternary
      Combinations with Nalidixic Acid and Nalidix Acid-Rutin Against Escherichia coli
      ATCC 25 922.
AB  - In order to determine the existence of synergism, the bacteriostatic action of
      flavonoids against Escherichia coli ATCC 25 922 between dihydroxylated chalcones
      and a clinically interesting conventional antibiotic, binary combinations of 2',3
      dihydroxychalcone, 2',4-dihydroxychalcone and 2',4'-dihydroxychalcone with
      nalidixic acid and its ternary combinations with rutin (inactive flavonoid) were
      assayed against this Gram negative bacterium. Using a kinetic-turbidimetric
      method, growth kinetics were monitored in broths containing variable amounts of
      dihydroxychalcone alone, combinations of dihydroxychalcone variable concentration
      nalidixic acid constant concentration and dihydroxychalcone variable
      concentration-nalidixic acid constant concentration-rutin constant concentration,
      respectively. The minimum inhibitory concentrations of dihydroxychalcones alone
      and its binary and ternary combinations were evaluated. All chalcones, and their
      binary and ternary combinations showed antibacterial activity, being rutin an
      excellent synergizing for the dihydroxychalcone-nalidixic acid binary combination
      against E. coli ATCC 25 922. Thus, this synergistic effect is an important way
      that could lead to the development of new combination antibiotics against
      infections caused by E. coli. 

PMID- 24293724
TI  - Degradation of 2,4,6-Trinitrophenol (TNP) by Arthrobacter sp. HPC1223 Isolated
      from Effluent Treatment Plant.
AB  - Arthrobacter sp. HPC1223 (Genebank Accession No. AY948280) isolated from
      activated biomass of effluent treatment plant was capable of utilizing 2,4,6
      trinitrophenol (TNP) under aerobic condition at 30  degrees C and pH 7 as
      nitrogen source. It was observed that the isolated bacteria utilized TNP up to 70
      % (1 mM) in R2A media with nitrite release. The culture growth media changed into
      orange-red color hydride-meisenheimer complex at 24 h as detected by HPLC. Oxygen
      uptake of Arthrobacter HPC1223 towards various nitro/amino substituted phenols
      such as dinitrophenol (1.2 nmol/min/mg cells), paranitrophenol (0.9 nmol/min/mg
      cells), 2-aminophenol (0.75 nmol/min/mg cells), p-aminophenol (0.4 nmol/min/mg
      cells), phenol (0.56 nmol/min/mg cells) and TNP (2.42 nmol/min/mg cell) was
      analysed, which showed its additional characteristic of broad substrate catabolic
      capacity. The present study thus report a novel indigenous bacteria isolated from
      activated sludge utilized TNP and has broad catabolic potential towards
      substituted phenols. 

PMID- 24293725
TI  - Optimization of Cultivating Conditions for Triterpenoids Production from Antrodia
      cinnmomea.
AB  - The submerged cultivating conditions for triterpenoids production from Antrodia
      cinnamomea were optimized using uniform design method and the one-factor-at-a
      time method was adopted to investigate the effect of plants oils and glucose
      supply on triterpenoids production and mycelia growth. Corn starch and culturing
      time were identified as more significant variables for triterpenoids production.
      The optimal conditions for triterpenoids production was 20.0 g/L corn starch,
      20.0 g/L wheat bran, 1.85 g/L MgSO4, initial pH 3 and 16 days of cultivation. In
      addition, investigation of plant oils and glucose supply showed that 0.3 % (v/v)
      olive oil supply at the beginning of fermentation stimulated mycelia growth and
      significantly increased triterpenoids production; 0.2 % (w/v) glucose supplement
      at 10th day enhanced production of triterpenoids with slight effect on biomass,
      which is reported for the first time. The triterpenoids production experimentally
      obtained under the optimal conditions was 7.23 % (w/w). The uniform design method
      may be used to optimize many environmental and genetic factors such as
      temperature and agitation that can also affect the triterpenoids production from
      A. cinnamomea. 

PMID- 24293726
TI  - Astaxanthin Synthesis by Yeast Xanthophyllomyces dendrorhous and its Mutants on
      Media Based on Plant Extracts.
AB  - The study evaluated the effect of media based on plant extracts: potato, carrot
      and barley malt broth, on growth and astaxanthin synthesis by yeast
      Xanthophyllomyces dendrorhous DSM 5626 and its mutants. The carrot medium
      promoted carotenogenesis most effectively. In cultures on this medium the highest
      volumetric and cellular concentrations of astaxanthin were recorded for four out
      of five tested strains. Also the share of astaxanthin in the total carotenoids
      produced by the tested strains was the highest. 

PMID- 24293727
TI  - Identification of Outer Membrane Proteins Altered in Response to UVC-Radiation in
      Vibrio parahaemolyticus and Vibrio alginolyticus.
AB  - Vibrio parahaemolyticus and V. alginolyticus, marine foodborne pathogens, were
      treated with UVC-radiation (240 J/m(2)) to evaluate alterations in their outer
      membrane protein profiles. Outer membrane protein patterns of UVC-irradiated
      bacteria were found altered when analyzed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. Altered proteins were identified by mass
      spectrometry (MS and MS/MS) and analysis revealed that OmpW, OmpA, Long-chain
      fatty acid transport protein, Outer membrane receptor protein, Putative
      uncharacterized protein VP0167, Maltoporin (lamB), Polar flagellin B/D,
      Agglutination protein Peptidoglycan-associated lipoprotein and MltA-interacting
      protein MipA were appeared, thereby they can be considered as UVC-stress proteins
      in some vibrios. In addition, expression of OmpK decreased to non-detectable
      level. Furthermore, we observed a decrease or an increase in the expression level
      of other outer membrane proteins. 

PMID- 24293728
TI  - Culture Age, Intracellular Ca(2+) Concentration, and Protein Phosphorylation in
      Encystment-Induced Colpoda cucullus.
AB  - In Colpoda cucullus, intracellular Ca(2+) mediates the encystment induction and
      protein phosphorylation that occur just prior to morphogenetic transformation
      into the resting form. When rapidly growing cells were stimulated to encyst,
      encystment was not readily induced, and the protein phosphorylation level was
      lower. On the other hand, in post-growing cells stimulated to encyst, the
      encystment rate and protein phosphorylation level were elevated. These results
      suggest that protein phosphorylation is closely linked to encystment induction.
      Why, then, are the protein phosphorylation level and encystment rate difficult to
      elevate in the rapidly growing cells? Fura 2 ratiometry showed that the
      intracellular Ca(2+) concentration (F340/F380 ratio) was raised in rapidly
      growing cells as well as in post-growing cells when the cells were stimulated to
      encyst. It is presumed that the Ca(2+)-mediated signal transduction pathways for
      protein phosphorylation and encystment may be triggered in rapidly growing cells,
      but downstream certain steps may be suppressed by certain intracellular
      components. 

PMID- 24293729
TI  - A Shortcut to the Optimization of Cellulase Production Using the Mutant
      Trichoderma reesei YC-108.
AB  - Trichoderma reesei YC-108, a strain isolated by a kind of newly invented plate
      was found to over produce cellulase and it was then used as a cellulase producer.
      To get the maximum amount of cellulase, the combination of the medium
      ingredients, which has a profound influence on metabolic pathway was optimized
      using response surface methodology. The optimum composition was found to be 24.63
      g/L wheat bran, 30.78 g/L avicel, and 19.16 g/L soya-bean cake powder. By using
      the optimized medium, the filter paper activity (FPA) increased nearly five times
      to 15.82 IU/mL in a 30 L stirred fermenter, carboxymethyl cellulase activity
      (CMCase) was increased from 83.02 to 628.05 IU/mL and the CMCase/FPA ratio was
      nearly doubled compared with the parent strain at initial medium. 

PMID- 24293730
TI  - Antimicrobial and Antimycobacterial Activities of Methyl Caffeate Isolated from
      Solanum torvum Swartz. Fruit.
AB  - ABSTRACT: Solanum torvum Swartz. (Solanaceae) fruit is traditionally used for the
      treatment of bacterial and fungal infections. The methanolic extract was
      subjected to activity guided fractionation by column chromatography over silica
      gel. The structure of the compound was elucidated using physical and
      spectroscopic data. The antimicrobial activity was screened using five Gram
      positive bacteria, six Gram-negative bacteria, seven clinical isolates and four
      fungi. Antimycobacterial activity was screened against two Mycobacterium strains.
      The zone of inhibition by methyl caffeate ranged from 0 to 22 mm. The lowest
      minimum inhibitory concentration (MIC) values of methyl caffeate were: 50 MUg/ml
      against P. vulgaris, 25 MUg/ml against K. pneumoniae (ESBL-3971), 8 MUg/ml
      against M. tuberculosis (H(37)Rv) and 8 MUg/ml against M. tuberculosis (Rif(R)).
      Methyl caffeate showed moderate antimicrobial and prominent antimycobacterial
      activities. Methyl caffeate can be evaluated further for drug development.

PMID- 24293731
TI  - Cloning, Expression, and Characterization of an GHF 11 Xylanase from Aspergillus
      niger XZ-3S.
AB  - A xylanase gene (xynZF-2) from the Aspergillus niger XZ-3S was cloned and
      expressed in Escherichia coli. The coding region of the gene was separated by
      only one intron with the 68 bp in length. It encoded 225 amino acid residues of a
      protein with a calculated molecular weight of 24.04 kDa plus a signal peptide of
      18 amino acids. The amino acid sequence of the xynZF-2 gene had a high similarity
      with those of family 11 of glycosyl hydrolases reported from other
      microorganisms. The mature peptide encoding cDNA was subcloned into pET-28a(+)
      expression vector. The resultant recombinant plasmid pET-28a-xynZF-2 was
      transformed into E. coli BL21(DE3), and finally the recombinant strain BL21/xynZF
      2 was obtained. A maximum activity of 42.33 U/mg was gained from cellular of E.
      coli BL21/xynZF-2 induced by IPTG. The optimum temperature and pH for recombinant
      enzyme which has a good stability in alkaline conditions were 40  degrees C and
      5.0, respectively. Fe(3+) had an active effect on the enzyme obviously. 

PMID- 24293732
TI  - Spontaneous Super-Swarming Derivatives of Azospirillum brasilense Sp245 have
      Different DNA Profiles and Behavior in the Presence of Various Nitrogen Sources.
AB  - Azospirillum brasilense swims in liquid environments and swarms in semisolid
      media. Five variants of A. brasilense Sp245, Sp245.P1-Sp245.P5, which swarmed
      faster than Sp245 in a semisolid malate-salt medium, have been isolated. In
      Sp245.P1-Sp245.P4, a new megaplasmid was revealed instead of an indigenous 85-MDa
      plasmid (p85). By polymerase chain reactions (PCR) with primers to the segments
      of p85 important for proper bacterial motility/flagellation and for dissimilatory
      nitrite and NO reduction, that DNA of p85 was found retained by all the variants.
      In ERIC- and RAPD-PCR, microdiversity between the total DNAs of Sp245 and its
      variants was detected. Interstrain differences in growth characteristics in
      liquid peptone-succinate-salt medium with KNO3 or KNO2 and in KNO2
      production/consumption were revealed. Although all the variants swam and swarmed
      faster than Sp245 in the medium supplemented with NH4Cl or KNO3, not all of them
      could do so in MPSS with KNO2. 

PMID- 24293733
TI  - Cloning of a Family 11 Xylanase Gene from Bacillus amyloliquefaciens CH51
      Isolated from Cheonggukjang.
AB  - Bacillus amyloliquefaciens CH51, an isolate from cheonggukjang, Korean fermented
      soyfood, secretes several enzymes into culture medium. A gene encoding 19 kDa
      xylanase was cloned by PCR. Sequencing showed that the gene encoded a
      glycohydrolase family 11 xylanase and named xynA. xynAHis, xynA with additional
      codons for his-tag, was overexpressed in Escherichia coli BL21(DE3) using pET
      26b(+). XynAHis was purified using HisTrap affinity column. Km and Vmax of
      XynAHis were 0.363 mg/ml and 701.1 MUmol/min/mg, respectively with birchwood
      xylan as a substrate. The optimum pH and temperature were pH 4 and 25  degrees C,
      respectively. When xynA was introduced into Bacillus subtilis WB600, active XynA
      was secreted into culture medium. 

PMID- 24293734
TI  - The Determination of Assay for Laccase of Bacillus subtilis WPI with Two Classes
      of Chemical Compounds as Substrates.
AB  - Ligninolytic enzyme complexes are involved in lignin degradation. Among them
      laccases are outstanding because they use molecular oxygen as a co-substrate
      instead of hydrogen peroxide as used by peroxidases. Bacterial laccase of
      Bacillus genus was first reported in Claus and Filip (Microbiol Res 152:209-216,
      1997), since then more bacterial laccases have been found. In this research,
      laccase-producing bacteria were screened from pulp and paper industry wastewater,
      bagass and sugarcane rhizosphere. Nutrient agar medium containing 0.5 mM of
      guaiacol was used. It was observed that the laccase-producing strains developed
      brown colour from which 16 strains of Bacillus were identified. One of the
      isolated strains was identified as Bacillus subtilis WPI based on the results of
      biochemical tests and 16S rDNA sequence analysis. This strain showed laccase-like
      activity towards the oxidizing substrates ABTS and guaiacol. In this study
      guaiacol was used as the substrate of laccase activity assay. For determination
      of laccase activity of this isolate guaiacol was used as a substrate of assay for
      the first time in this study. SDS-PAGE and Native-PAGE confirmed the presence of
      laccase. 

PMID- 24293735
TI  - Antibacterial Screening of Secreted Compounds Produced by the Phase I Variant of
      Photorhabdus luminescens.
AB  - In this study, antibacterial activity of metabolites secreted by the phase I
      variant of Photorhabdus luminescens was investigated. Bioactivity of these
      metabolites was screened against 28 different bacterial species and strains.
      Bacterial sensitivity was determined by a modified-version of the Kirby-Bauer
      disk diffusion susceptibility method, whereas the phase I variant's culture
      permeate was utilized as the "antibacterial" agent. This investigation
      demonstrates that 11 of the 28 bacterial species tested were sensitive to at
      least one of the secreted compounds or a combination thereof. 

PMID- 24293736
TI  - A Simple Novel Agar Diffusion Method for Isolation of Indigenous Microalgae
      Chlamydomonas sp. CRP7 and Chlorella sp. CB4 from Operational Swampy Top Soil.
AB  - A simple agar diffusion method is developed where pure colony of Chlamydomonas
      sp. CRP7 was isolated from Chlorella sp. CB4 mixtures by passing through agar
      migration with a light exposure of 6,000 lux for 7 h. The main concept behind it
      is that Chlamydomonas has flagella and the rhodopsin pigment is attracted towards
      light. Thus the above two microalgae species can be separated from the mixtures
      as eye spot serves as a navigator and flagella serves as a propeller for
      Chlamydomonas spp. Further the genomic DNA was isolated and purified from the
      above mentioned two species after the separation from the mixtures. PCR
      amplification was carried out for ITS1, 5.8S and ITS2 regions. The amplified
      products were sequenced and the sequence analysis confirmed that they belong to
      Chlamydomonas sp. and Chlorella sp. This is an important augmentation for
      isolation and separation of microalgae. 

PMID- 24293737
TI  - India losing battle against multi drug resistant tuberculosis.

PMID- 24293739
TI  - Bone Histology Reveals a High Environmental and Metabolic Plasticity as a
      Successful Evolutionary Strategy in a Long-Lived Homeostatic Triassic
      Temnospondyl.
AB  - Evolutionary stasis (long-term stability of morphology in an evolving lineage) is
      a pattern for which explanations are usually elusive. The Triassic tetrapod
      Gerrothorax pulcherrimus, a gill-bearing temnospondyl, survived for 35 million
      years in the Germanic Basin of Central Europe persisting throughout the dinosaur
      dominated Late Triassic period. This evolutionary stasis coincides with the
      occurrence of this species in a wide range of habitats and environmental
      conditions. By the combination of palaeoecological and palaeohistological
      analyses, we found great ecological flexibility in G. pulcherrimus and present
      substantial evidence of developmental and metabolic plasticity despite the
      morphological stasis. We conclude that G. pulcherrimus could show the capacity to
      settle in water bodies too harsh or unpredictable for most other tetrapods. This
      would have been made possible by a unique life history strategy that involved a
      wide reaction norm, permitting adjustment to fluctuating conditions such as
      salinity and level of nutrients. Growth rate, duration of juvenile period, age at
      maturity, and life span were all subject to broad variation within specimens of
      G. pulcherrimus in one single lake and in between different lakes. In addition to
      providing a better understanding of fossil ecosystems, this study shows the
      potential of such a methodology to encourage palaeobiologists and evolutionary
      biologists to consider the mechanisms of variation in extant and fossil organisms
      by using a similar time-scope reference.

PMID- 24293738
TI  - Expression and Evolution of Short Wavelength Sensitive Opsins in Colugos: A
      Nocturnal Lineage That Informs Debate on Primate Origins.
AB  - A nocturnal activity pattern is central to almost all hypotheses on the adaptive
      origins of primates. This enduring view has been challenged in recent years on
      the basis of variation in the opsin genes of nocturnal primates. A correspondence
      between the opsin genes and activity patterns of species in Euarchonta-the
      superordinal group that includes the orders Primates, Dermoptera (colugos), and
      Scandentia (treeshrews)-could prove instructive, yet the basic biology of the
      dermopteran visual system is practically unknown. Here we show that the eye of
      the Sunda colugo (Galeopterus variegatus) lacks a tapetum lucidum and has an
      avascular retina, and we report on the expression and spectral sensitivity of
      cone photopigments. We found that Sunda colugos have intact short wavelength
      sensitive (S-) and long wavelength sensitive (L-) opsin genes, and that both
      opsins are expressed in cone photoreceptors of the retina. The inferred peak
      spectral sensitivities are 451 and 562 nm, respectively. In line with adaptation
      to nocturnal vision, cone densities are low. Surprisingly, a majority of S-cones
      coexpress some L-opsin. We also show that the ratio of rates of nonsynonymous to
      synonymous substitutions of exon 1 of the S-opsin gene is indicative of purifying
      selection. Taken together, our results suggest that natural selection has favored
      a functional S-opsin in a nocturnal lineage for at least 45 million years.
      Accordingly, a nocturnal activity pattern remains the most likely ancestral
      character state of euprimates.

PMID- 24293740
TI  - Structure of observed temperament in middle childhood.
AB  - Although much is known about the structure of adult temperament and personality,
      significantly less is known about the structure of child temperament. We examined
      the structure of child temperament in 205 seven-year-olds using observational
      measures. Exploratory factor analysis identified factors representing positive
      emotionality/sociability, disinhibition/anger, fear/behavioral inhibition, and
      sadness. The predictive validity of these dimensions was evaluated by examining
      their associations with children's internalizing and externalizing symptoms:
      positive emotionality/sociability showed positive associations with ADHD
      symptoms, disinhibition/anger showed positive associations with externalizing
      symptoms, fear/behavioral inhibition showed negative associations with ADHD and
      CD symptoms, and sadness showed positive associations with both internalizing and
      externalizing problems. These associations were consistent with extant literature
      on temperament and psychopathology, supporting the validity of the structure
      obtained.

PMID- 24293741
TI  - Listening with a foreign-accent: The interlanguage speech intelligibility benefit
      in Mandarin speakers of English.
AB  - This study examined the intelligibility of native and Mandarin-accented English
      speech for native English and native Mandarin listeners. In the latter group, it
      also examined the role of the language environment and English proficiency. Three
      groups of listeners were tested: native English listeners (NE), Mandarin-speaking
      Chinese listeners in the US (M-US) and Mandarin listeners in Beijing, China (M
      BJ). As a group, M-US and M-BJ listeners were matched on English proficiency and
      age of acquisition. A nonword transcription task was used. Identification
      accuracy for word-final stops in the nonwords established two independent
      interlanguage intelligibility effects. An interlanguage speech intelligibility
      benefit for listeners (ISIB-L) was manifest by both groups of Mandarin listeners
      outperforming native English listeners in identification of Mandarin-accented
      speech. In the benefit for talkers (ISIB-T), only M-BJ listeners were more
      accurate identifying Mandarin-accented speech than native English speech. Thus,
      both Mandarin groups demonstrated an ISIB-L while only the M-BJ group overall
      demonstrated an ISIB-T. The English proficiency of listeners was found to
      modulate the magnitude of the ISIB-T in both groups. Regression analyses also
      suggested that the listener groups differ in their use of acoustic information to
      identify voicing in stop consonants.

PMID- 24293742
TI  - 30 years of science and technology: the example of malaria.

PMID- 24293743
TI  - Low energy ion scattering: Determining overlayer thickness for functionalized
      gold nanoparticles.
AB  - With the widespread use of engineered nanoparticles for biomedical applications,
      detailed surface characterization is essential for ensuring reproducibility and
      the quality/suitability of the surface chemistry to the task at hand. One
      important surface property to be quantified is the overlayer thickness of self
      assembled monolayer (SAM) functionalized nanoparticles, as this information
      provides insight into SAM ordering and assembly. We demonstrate the application
      of high sensitivity low energy ion scattering (HS-LEIS) as a new analytical
      method for the fast thickness characterization of SAM functionalized gold
      nanoparticles (AuNPs). HS-LEIS demonstrates that a complete SAM is formed on 16
      mercaptohexadecanoic acid (C16COOH) functionalized 14 nm AuNPs. HS-LEIS also
      experimentally provides SAM thickness values that are in good agreement with
      previously reported results from simulated electron spectra for surface analysis
      (SESSA) analysis of X-ray photoelectron spectroscopy (XPS) data. These results
      indicate HS-LEIS is a valuable surface analytical method for the characterization
      of SAM functionalized nanomaterials.

PMID- 24293745
TI  - Melanin-concentrating hormone neurons promote and stabilize sleep.

PMID- 24293746
TI  - The role of Hcrt/Orx and MCH neurons in sleep-wake state regulation.

PMID- 24293747
TI  - MCH neurons: the end of the beginning.

PMID- 24293748
TI  - Role of MCH neurons in paradoxical (REM) sleep control.

PMID- 24293749
TI  - Relation of melanin concentrating hormone levels to sleep, emotion and hypocretin
      levels.

PMID- 24293750
TI  - MCH neurons are the primary sleep-promoting group.

PMID- 24293751
TI  - MCH neurons: vigilant workers in the night.

PMID- 24293752
TI  - Association of restless legs syndrome variants in Korean patients with restless
      legs syndrome.
AB  - STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians
      identified several allelic variants associated with increased risk of developing
      restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the
      pathogenic mechanisms of RLS are not entirely understood, it is becoming
      increasingly evident that many diseases such as RLS can be attributed to an
      epistasis. The study objectives were to evaluate whether the associations of RLS
      with all loci determined in previous GWAS for Caucasians can be replicated
      significantly for the Korean population and to elucidate whether an epistasis
      plays a role in the pathogenesis of RLS. DESIGN SETTING AND PARTICIPANTS: DNA
      from 320 patients with RLS and 320 age- and sex-matched controls were genotyped
      for variants in the RLS loci. MEASUREMENTS AND RESULTS: A significant association
      was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001,
      respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P
      < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002),
      according to the model of inheritance. The OR for the interaction between
      rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive
      model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the
      recessive model. There was no significant association between genotypes of all
      tested single nucleotide polymorphisms and the mean value of serum iron
      parameters. CONCLUSIONS: Our results suggest that the role of BTBD9 in the
      pathogenesis of restless legs syndrome is more universal across populations than
      previously reported and more efforts should be focused on the role of epistasis
      in the genetic architecture of restless legs syndrome.

PMID- 24293753
TI  - Testosterone conversion blockade increases breathing stability in healthy men
      during NREM sleep.
AB  - STUDY OBJECTIVES: Gender differences in the prevalence of sleep apnea/hypopnea
      syndrome may be mediated via male sex hormones. Our objective was to determine
      the exact pathway for a testosterone-mediated increased propensity for central
      sleep apnea via blockade of the 5alpha-reductase pathway of testosterone
      conversion by finasteride. DESIGN: Randomization to oral finasteride vs. sham,
      single-center study. SETTING: Sleep research laboratory. PARTICIPANTS: Fourteen
      healthy young males without sleep apnea. INTERVENTION: Hypocapnia was induced via
      brief nasal noninvasive positive pressure ventilation during stable NREM sleep.
      Cessation of mechanical ventilation resulted in hypocapnic central apnea or
      hypopnea. MEASUREMENTS AND RESULTS: The apnea threshold (AT) was defined as the
      end-tidal CO2(P(ET)CO2) that demarcated the central apnea closest to the eupneic
      P(ET)CO2. The CO2 reserve was defined as the difference in P(ET)CO2 between
      eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and
      repeated after at a minimum of 1 month. Administration of finasteride resulted in
      decreased serum dihydrotestosterone. In the finasteride group, the eupneic
      ventilatory parameters were unchanged; however, the AT was decreased (38.9 +/-
      0.6 mm Hg vs.37.7 +/- 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (
      2.5 +/- 0.3 mm Hg vs. -3.8 +/- 0.5 mm Hg, P = 0.003) at follow-up, with a
      significantly lower hypocapnic ventilatory response, thus indicating increased
      breathing stability during sleep. No significant changes were noted in the sham
      group on follow-up study. CONCLUSIONS: Inhibition of testosterone action via the
      5alpha-reductase pathway may be effective in alleviating breathing instability
      during sleep, presenting an opportunity for novel therapy for central sleep apnea
      in selected populations.

PMID- 24293754
TI  - Effectiveness of three sleep apnea management alternatives.
AB  - RATIONALE: Home respiratory polygraphy (HRP) may be a cost-effective alternative
      to polysomnography (PSG) for diagnosis and treatment election in patients with
      high clinical probability of obstructive sleep apnea (OSA), but there is
      conflicting evidence on its use for a wider spectrum of patients. OBJECTIVES: To
      determine the efficacy and cost of OSA management (diagnosis and therapeutic
      decision making) using (1) PSG for all patients (PSG arm); (2) HRP for all
      patients (HRP arm); and (3) HRP for a subsample of patients with high clinical
      probability of being treated with continuous positive airway pressure (CPAP) and
      PSG for the remainder (elective HRP arm). METHODS: Multicentric study of 366
      patients with intermediate-high clinical probability of OSA, randomly subjected
      to HRP and PSG. We explored the diagnostic and therapeutic decision agreements
      between the PSG and both HRP arms for several HRP cutoff points and calculated
      costs for equal diagnostic and/or therapeutic decision efficacy. RESULTS: For
      equal diagnostic and therapeutic decision efficacy, PSG arm costs were 18% higher
      than HRP arm costs and 20% higher than elective HRP arm costs. HRP arm costs
      tended to be lower than elective HRP arm costs, and both tended to be lower than
      PSG arm costs if patient costs were omitted. CONCLUSION: Home respiratory
      polygraphy is a less costly alternative than polysomnography for the diagnosis
      and therapeutic decision making for patients with suspected obstructive sleep
      apnea. We found no advantage in cost terms, however, in using home respiratory
      polygraphy for all patients or home respiratory polygraphy for the most
      symptomatic patients and polysomnography for the rest.

PMID- 24293755
TI  - A subset of cholinergic mushroom body neurons requires Go signaling to regulate
      sleep in Drosophila.
AB  - STUDY OBJECTIVES: Identifying the neurochemistry and neural circuitry of sleep
      regulation is critical for understanding sleep and various sleep disorders. Fruit
      flies display sleep-like behavior, sharing essential features with sleep of
      vertebrate. In the fruit fly's central brain, the mushroom body (MB) has been
      highlighted as a sleep center; however, its neurochemical nature remains unclear,
      and whether it promotes sleep or wake is still a topic of controversy. DESIGN: We
      used a video recording system to accurately monitor the locomotor activity and
      sleep status. Gene expression was temporally and regionally manipulated by heat
      induction and the Gal4/UAS system. MEASUREMENTS AND RESULTS: We found that
      expressing pertussis toxin (PTX) in the MB by c309-Gal4 to block Go activity led
      to unique sleep defects as dramatic sleep increase in daytime and fragmented
      sleep in nighttime. We narrowed down the c309-Gal4 expressing brain regions to
      the MB alpha/beta core neurons that are responsible for the Go-mediated sleep
      effects. Using genetic tools of neurotransmitter-specific Gal80 and RNA
      interference approach to suppress acetylcholine signal, we demonstrated that
      these MB alpha/beta core neurons were cholinergic and sleep-promoting neurons,
      supporting that Go mediates an inhibitory signal. Interestingly, we found that
      adjacent MB alpha/beta neurons were also cholinergic but wake-promoting neurons,
      in which Go signal was also required. CONCLUSION: Our findings in fruit flies
      characterized a group of sleep-promoting neurons surrounded by a group of wake
      promoting neurons. The two groups of neurons are both cholinergic and use Go
      inhibitory signal to regulate sleep.

PMID- 24293756
TI  - Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia.
AB  - STUDY OBJECTIVES: Investigate the hypnotic effects of repeated doses of
      neurokinin-1 receptor antagonist, vestipitant, in primary insomnia. DESIGN:
      Randomized, double-blind, placebo-controlled 28-day parallel-group study.
      SETTING: Eleven sleep centers in Germany. PATIENTS: One hundred sixty-one
      patients with primary insomnia. INTERVENTIONS: Patients received vestipitant (15
      mg) or placebo for 28 days; 2-night polysomnographic assessment occurred on
      nights 1/2 and 27/28. MEASUREMENTS AND RESULTS: Wake after sleep onset (WASO) was
      improved on nights 1/2 and 27/28 (ratio, vestipitant versus placebo [95%
      confidence interval]: 0.76 [0.65, 0.90], P = 0.001 and 0.79 [0.65, 0.96], P =
      0.02, respectively), demonstrating maintenance of the effect following repeated
      dosing. Latency to persistent sleep was shorter with vestipitant on nights 1/2 (P
      = 0.0006 versus placebo), but not on nights 27/28. Total sleep time (TST)
      improved with vestipitant (nights 1/2: P < 0.0001, nights 27/28: P = 0.02 versus
      placebo). Next-day cognitive function tests demonstrated no residual effects of
      vestipitant (P > 0.05 versus placebo). Adverse events (AEs) occurred in 25% of
      vestipitant patients versus 22% for placebo. Headache was the most common AE (8%
      of vestipitant patients versus 9% for placebo). CONCLUSIONS: Vestipitant improved
      sleep maintenance in patients with primary insomnia, with no associated next-day
      cognitive impairment. The effects on wake after sleep onset and total sleep time
      were maintained following repeated dosing.

PMID- 24293757
TI  - Circulating FABP4 and FABP5 levels are differently linked to OSA severity and
      treatment.
AB  - OBJECTIVE: To evaluate circulating adipocyte and epidermal fatty acid-binding
      protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea
      (OSA), as well as the effects of continuous positive airway pressure (CPAP)
      treatment. METHODS: Our cross-sectional study included 125 patients. After
      polysomnography, 58 participants met the criteria for CPAP treatment and were
      included in a closed cohort study of 8 weeks of CPAP treatment. General
      anthropometric and biochemical data and circulating FABP4 and FABP5 levels were
      determined in all patients at baseline and after CPAP treatment in those
      receiving this therapy. RESULTS: Circulating FABP4 but not FABP5 levels were
      higher in patients with OSA (P = 0.003). FABP4 but not FABP5 values were
      associated with parameters of OSA severity independently of age, gender,
      adiposity and insulin resistance (P < 0.05). FABP4 but not FABP5 concentrations
      were determinants of OSA presence (OR: 1.11, P = 0.010) and severity (OR: 1.06, P
      = 0.020). After CPAP treatment, FABP4 levels decreased in the more severe
      patients (P = 0.019), while FABP5 levels increased in all patients (P < 0.001).
      CONCLUSIONS: FABP4 is directly associated with obstructive sleep apnea severity
      and did not change with continuous positive airway pressure treatment, while
      FABP5 was not associated with obstructive sleep apnea severity and increased with
      continuous positive airway pressure treatment. FABP4 and FABP5 have different
      associations with obstructive sleep apnea. FABP4 but not FABP5 could be
      considered a marker of metabolic alterations in obstructive sleep apnea patients.

PMID- 24293758
TI  - Kv2.2: a novel molecular target to study the role of basal forebrain GABAergic
      neurons in the sleep-wake cycle.
AB  - STUDY OBJECTIVES: The basal forebrain (BF) has been implicated as an important
      brain region that regulates the sleep-wake cycle of animals. Gamma-aminobutyric
      acidergic (GABAergic) neurons are the most predominant neuronal population within
      this region. However, due to the lack of specific molecular tools, the roles of
      the BF GABAergic neurons have not been fully elucidated. Previously, we have
      found high expression levels of the Kv2.2 voltage-gated potassium channel on
      approximately 60% of GABAergic neurons in the magnocellular preoptic area and
      horizontal limb of the diagonal band of Broca of the BF and therefore proposed it
      as a potential molecular target to study this neuronal population. In this study,
      we sought to determine the functional roles of the Kv2.2-expressing neurons in
      the regulation of the sleep-wake cycle. DESIGN: Sleep analysis between two
      genotypes and within each genotype before and after sleep deprivation. SETTING:
      Animal sleep research laboratory. PARTICIPANTS: Adult mice. Wild-type and Kv2.2
      knockout mice with C57/BL6 background. INTERVENTIONS: EEG/EMG recordings from the
      basal state and after sleep-deprivation which was induced by mild agitation for 6
      h. RESULTS: Immunostaining of a marker of neuronal activity indicates that these
      Kv2.2-expressing neurons appear to be preferentially active during the wake
      state. Therefore, we tested whether Kv2.2-expressing neurons in the BF are
      involved in arousal using Kv2.2-deficient mice. BF GABAergic neurons exhibited
      augmented expression of c-Fos. These knockout mice exhibited longer consolidated
      wake bouts than wild-type littermates, and that phenotype was further exacerbated
      by sleep deprivation. Moreover, in-depth analyses of their cortical
      electroencephalogram revealed a significant decrease in the delta-frequency
      activity during the nonrapid eye movement sleep state. CONCLUSIONS: These results
      revealed the significance of Kv2.2-expressing neurons in the regulation of the
      sleep-wake cycle.

PMID- 24293759
TI  - Intermittent hypoxia exacerbates pancreatic beta-cell dysfunction in a mouse
      model of diabetes mellitus.
AB  - STUDY OBJECTIVES: The effects of intermittent hypoxia (IH) on pancreatic function
      in the presence of diabetes and the underlying mechanisms are unclear. We
      hypothesized that IH would exacerbate pancreatic beta-cell dysfunction and alter
      the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2
      diabetes. DESIGN: TH mice were exposed for 14 d to either 8 h of IH or
      intermittent air (IA), followed by an intraperitoneal glucose tolerance test
      (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by
      using a beta3-adrenergic receptor (AR) agonist. MEASUREMENTS AND RESULTS: During
      IH, pancreatic tissue pO2 decreased from 20.4 +/- 0.9 to 5.7 +/- 2.6 mm Hg, as
      determined by electron paramagnetic resonance oximetry. TH mice exposed to IH
      exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the
      insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group
      showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the beta
      AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the
      total free fatty acids and saturated fatty acids (palmitic and stearic acids),
      and decreased levels of the monounsaturated fatty acids in the pancreas and
      plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin
      secretion and decreased islet cell viability. CONCLUSIONS: Intermittent hypoxia
      increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent
      model of diabetes. An increase in free fatty acids and a shift in composition
      towards long chain saturated fatty acid species appear to mediate these effects.

PMID- 24293760
TI  - The complex associations among sleep quality, anxiety-depression, and quality of
      life in patients with extreme obesity.
AB  - INTRODUCTION: Sleep duration and quality have been associated with obesity. Sleep
      disturbance has been reported to be associated with stress and depression among
      non-obese populations, but these relationships have not been previously examined
      in the obese population. The objective of the current study was to examine the
      complex associations among sleep disturbance, quality of life, anxiety, and
      depression in a patient sample with severe obesity. METHODS: Two hundred seventy
      consecutively recruited patients with a mean body mass index (BMI) of 47.0 kg/m2
      were studied. The correlation coefficient, multiple linear regressions, and
      structural equation modeling (SEM) analysis were used to evaluate the association
      between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale
      (ESS), Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Hospital Anxiety
      and Depression Scale (HADS). RESULTS: The mean (standard deviation; SD) PSQI
      score was 8.59 (5.11), and mean ESS score was 8.84 (5.79). After controlling for
      potential confounders, poor sleep quality and excessive daytime sleepiness were
      found to be significantly associated of all the components of IWQOL-Lite;
      physical function (beta = -0.32, beta = -0.27; P < 0.01), self-esteem (beta = 
      0.23, beta = -0.30; P < 0.05), sexual-life (beta = -0.30, beta = -0.35; P <
      0.05), public distress (beta = -0.39, beta = -0.39; P < 0.01), and work (beta = 
      0.26, beta = -0.48; P < 0.01). We also found that the PSQI global score had a
      positive significant association with anxiety (beta = 0.29; P = 0.01) and
      depression (beta = 0.31; P = 0.01) components of HADS. CONCLUSION: Poor sleep
      quality was strongly associated with mood disturbance and poor quality of life
      among extremely obese patients. Future interventions are needed to address sleep
      disturbance to prevent further development of psychological co-morbidity and
      potentially worsening of obesity among these individuals.

PMID- 24293761
TI  - Now you hear me, now you don't: eyelid closures as an indicator of auditory task
      disengagement.
AB  - STUDY OBJECTIVES: Eyelid closures in fatigued individuals signify task
      disengagement in attention-demanding visual tasks. Here, we studied how varying
      degrees of eyelid closure predict responses to auditory stimuli depending on
      whether a participant is well rested or sleep deprived. We also examined time-on
      task effects and how more and less vulnerable individuals differed in frequency
      of eye closures and lapses. DESIGN: Six repetitions of an auditory vigilance task
      were performed in each of two sessions: rested wakefulness (RW) and total sleep
      deprivation (TSD) (order counterbalanced). SETTING: Sleep laboratory.
      PARTICIPANTS: Nineteen healthy young adults (mean age: 22 +/- 2.8 y; 11 males).
      INTERVENTION: Approximately 24 h of TSD. MEASUREMENTS AND RESULTS: Eyelid closure
      was rated on a 9-point scale (1 = fully closed to 9 = fully opened) using video
      segments time-locked to the auditory event. Eyes-open trials predominated during
      RW, but different degrees of eye closure were uniformly distributed during TSD.
      The frequency of lapses (response time > 800 ms or nonresponses) to auditory
      stimuli increased dramatically with greater degrees of eye closure, but the
      association was strong only during TSD. There were significant within-run time-on
      task effects on eye closure and auditory lapses that were exacerbated by TSD.
      Participants who had more auditory lapses during TSD (more vulnerable) had
      greater variability in their eyelid closures. CONCLUSIONS: Eyelid closures are a
      strong predictor of auditory task disengagement in the sleep-deprived state but
      are less relevant during rested wakefulness. Individuals relatively more impaired
      in this auditory vigilance task during total sleep deprivation display oculomotor
      evidence for greater state instability.

PMID- 24293762
TI  - Rapid eye movement and non-rapid eye movement sleep contributions in memory
      consolidation and resistance to retroactive interference for verbal material.
AB  - STUDY OBJECTIVES: To test the hypothesis that rapid eye movement (REM) sleep
      contributes to the consolidation of new memories, whereas non-rapid eye movement
      (NREM) sleep contributes to the prevention of retroactive interference. DESIGN:
      Randomized, crossover study. SETTING: Two sessions of either a morning nap or
      wakefulness. PARTICIPANTS: Twenty-five healthy young adults. INTERVENTIONS:
      Declarative learning of word pairs followed by a nap or a wake interval, then
      learning of interfering word pairs and delayed recall of list A. MEASUREMENTS AND
      RESULTS: After a restricted night (24:00-06:00), participants learned a list of
      word pairs (list A). They were then required to either take a nap or stay awake
      during 45 min, after which they learned a second list of word pairs (list B) and
      then had to recall list A. Fifty percent of word pairs in list B shared the first
      word with list A, resulting in interference. Ten subjects exhibited REM sleep
      whereas 13 subjects exhibited NREM stage 3 (N3) sleep. An interference effect was
      observed in the nap but not in the wake condition. In post-learning naps, N3
      sleep was associated with a reduced interference effect, which was not the case
      for REM sleep. Moreover, participants exhibiting N3 sleep in the post-learning
      nap condition also showed a reduced interference effect in the wake condition,
      suggesting a higher protection ability against interference. CONCLUSION: Our
      results partly support the hypothesis that non-rapid eye movement sleep
      contributes in protecting novel memories against interference. However, rapid eye
      movement sleep-related consolidation is not evidenced.

PMID- 24293763
TI  - Altered nigrostriatal and nigrocortical functional connectivity in rapid eye
      movement sleep behavior disorder.
AB  - STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is a condition
      closely associated with Parkinson disease (PD). RBD is a sleep disturbance that
      frequently manifests early in the development of PD, likely reflecting disruption
      in normal functioning of anatomical areas affected by neurodegenerative
      processes. Although specific neuropathological aspects shared by RBD and PD have
      yet to be fully documented, further characterization is critical to discovering
      reliable biomarkers that predict PD onset. In the current study, we tested the
      hypothesis of altered functional connections of the substantia nigra (SN) in
      patients in whom RBD was diagnosed. DESIGN: Between-groups, single time point
      imaging. SETTING: UTHSC-H 3 telsa MRI center. PARTICIPANTS: Ten patients with
      RBD, 11 patients with PD, and 10 age-matched controls. INTERVENTIONS: NA.
      MEASUREMENTS AND RESULTS: We measured correlations of SN time series using
      resting state blood oxygen level-dependent functional magnetic resonance imaging
      (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD,
      patients in whom PD was diagnosed, and age-matched controls. Using voxelwise
      analysis of variance, different correlations (P < 0.01, whole-brain corrected)
      between left SN and left putamen were found in patients with RBD compared with
      controls and patients with PD. SN correlations with right cuneus/precuneus and
      superior occipital gyrus were significantly different for patients with RBD
      compared with both controls and patients with PD. CONCLUSIONS: The results
      suggest that altered nigrostriatal and nigrocortical connectivity characterizes
      rapid eye movement sleep behavior disorder before onset of obvious motor
      impairment. The functional changes are discussed in the context of degeneration
      in dopaminergic and cognition-related networks.

PMID- 24293764
TI  - Electroencephalographic findings related with mild cognitive impairment in
      idiopathic rapid eye movement sleep behavior disorder.
AB  - STUDY OBJECTIVES: Mild cognitive impairment (MCI) and electroencephalographic
      (EEG) slowing have been reported as common findings of idiopathic rapid eye
      movement (REM) sleep behavior disorder (iRBD) and alpha-synucleinopathies. The
      objective of this study is to clarify the relation between MCI and physiological
      markers in iRBD. DESIGN: Cross-sectional study. SETTING: Yoyogi Sleep Disorder
      Center. PATIENTS OR PARTICIPANTS: Thirty-one patients with iRBD including 17
      younger patients with iRBD (younger than 70 y) and 17 control patients for the
      younger patients with iRBD. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
      Montreal Cognitive Assessment (MoCA) and n-polysomnogram (PSG) were conducted of
      all participants. In patients with iRBD, the factors associated with MCI were
      explored among parameters of REM sleep without atonia (RWA), score of Sniffin'
      Sticks Test (threshold-discrimination-identification [TDI] score), RBD morbidity,
      and RBD severity evaluated with the Japanese version of the RBD questionnaire
      (RBDQ-JP). The younger iRBD group showed significantly lower alpha power during
      wake and lower MoCA score than the age-matched control group. MCI was detected in
      13 of 17 patients (76.5%) on MoCA in this group. Among patients wtih iRBD, the
      MoCA score negatively correlated with age, proportion of slow wave sleep, TDI
      score, and EEG spectral power. Multiple regression analysis provided the
      following equation: MoCA score = 50.871-0.116*age -5.307*log (delta power during
      REM sleep) + 0.086*TDI score (R2 = 0.598, P < 0.01). The standardized partial
      regression coefficients were -0.558 for age, -0.491 for log (delta power during
      REM sleep), and 0.357 for TDI score (F = 9.900, P < 0.001). CONCLUSIONS:
      Electroencephalographic slowing, especially during rapid eye movement sleep and
      olfactory dysfunction, was revealed to be associated with cognitive decline in
      idiopathic rapid eye movement sleep behavior disorder.

PMID- 24293765
TI  - Symptoms of insomnia among patients with obstructive sleep apnea before and after
      two years of positive airway pressure treatment.
AB  - STUDY OBJECTIVES: To assess the changes of insomnia symptoms among patients with
      obstructive sleep apnea (OSA) from starting treatment with positive airway
      pressure (PAP) to a 2-y follow-up. DESIGN: Longitudinal cohort study. SETTING:
      Landspitali--The National University Hospital of Iceland. PARTICIPANTS: There
      were 705 adults with OSA who were assessed prior to and 2 y after starting PAP
      treatment. INTERVENTION: PAP treatment for OSA. MEASUREMENTS AND RESULTS: All
      patients underwent a medical examination along with a type 3 sleep study and
      answered questionnaires on health and sleep before and 2 y after starting PAP
      treatment. The change in prevalence of insomnia symptoms by subtype was assessed
      by questionnaire and compared between individuals who were using or not using PAP
      at follow-up. Symptoms of middle insomnia were most common at baseline and
      improved significantly among patients using PAP (from 59.4% to 30.7%, P < 0.001).
      Symptoms of initial insomnia tended to persist regardless of PAP treatment, and
      symptoms of late insomnia were more likely to improve among patients not using
      PAP. Patients with symptoms of initial and late insomnia at baseline were less
      likely to adhere to PAP (odds ratio [OR] 0.56, P = 0.007, and OR 0.53, P < 0.001,
      respectively). CONCLUSION: Positive airway pressure treatment significantly
      reduced symptoms of middle insomnia. Symptoms of initial and late insomnia,
      however, tended to persist regardless of positive airway pressure treatment and
      had a negative effect on adherence. Targeted treatment for insomnia may be
      beneficial for patients with obstructive sleep apnea comorbid with insomnia and
      has the potential to positively affect adherence to positive airway pressure.

PMID- 24293766
TI  - Cerebrovascular control is altered in healthy term infants when they sleep prone.
AB  - STUDY OBJECTIVES: Sudden infant death syndrome (SIDS) is a leading cause of
      infant death, and prone sleeping is the major risk factor. Prone sleeping impairs
      arousal from sleep and cardiovascular control in infants at 2-3 months,
      coinciding with the highest risk period for SIDS. We hypothesized that prone
      sleeping would also alter cerebrovascular control, and aimed to test this
      hypothesis by examining responses of cerebral oxygenation to head-up tilts (HUTs)
      over the first 6 months after birth. STUDY DESIGN AND PARTICIPANTS: Seventeen
      healthy full-term infants were studied at 2-4 weeks, 2-3 months, and 5-6 months
      of age using daytime polysomnography, with the additional measurements of blood
      pressure (BP, FinometerTM, Finometer Medical Systems, The Netherlands) and
      cerebral tissue oxygenation index (TOI, NIRO 200, Hamamatsu Photonics KK, Japan).
      HUTs were performed in active sleep (AS) and quiet sleep (QS) in both prone and
      supine positions. RESULTS: When infants slept in the prone position, a sustained
      increase in TOI (P < 0.05) occurred following HUTs, except in QS at 2-3 months
      when TOI was unchanged. BP was either unchanged or fell below baseline during the
      sustained TOI increase, signifying cerebro-vasodilatation. In contrast, when
      infants slept supine, TOI did not change after HUTs, except in QS at 2-3 and 5-6
      months when TOI dropped below baseline (P < 0.05). CONCLUSIONS: When infants
      slept in the prone position, cerebral arterial vasodilation and increased
      cerebral oxygenation occurred during head-up tilts, possibly as a protection
      against cerebral hypoxia. Absence of the vasodilatory response during quiet sleep
      at 2-3 months possibly underpins the decreased arousability from sleep and
      increased risk for sudden infant death syndrome at this age.

PMID- 24293767
TI  - Circadian variation of heart rate variability across sleep stages.
AB  - STUDY OBJECTIVES: Nocturnal cardiovascular events are more frequent at the
      beginning and end of the night. It was proposed that this pattern reflects the
      nocturnal distribution of sleep and sleep stages. Using heart rate variability
      (HRV), we recently showed an interaction between the circadian system and
      vigilance states on the regulation of cardiac rhythmicity. Here, we further
      investigate this interaction in order to clarify the specific effects of sleep
      stages on the regulation of the heart. DESIGN: Participants underwent a 72-h
      ultradian sleep-wake cycle procedure in time isolation consisting of alternating
      60-min wake episodes in dim light and 60-min nap opportunities in total darkness.
      SETTING: Time isolation suite. PATIENTS OR PARTICIPANTS: Fifteen healthy young
      participants; two were subsequently excluded. INTERVENTIONS: N/A. MEASUREMENTS
      AND RESULTS: The current study revealed that sleep onset and progression to
      deeper sleep stages was associated with a shift toward greater parasympathetic
      modulation, whereas rapid eye movement (REM) sleep was associated with a shift
      toward greater sympathetic modulation. We found a circadian rhythm of heart rate
      (HR) and high-frequency power during wakefulness and all non-REM sleep stages. A
      significant circadian rhythm of HR and sympathovagal balance of the heart was
      also observed during REM sleep. During slow wave sleep, maximal parasympathetic
      modulation was observed at ~02:00, whereas during REM sleep, maximal sympathetic
      modulation occurred in the early morning. CONCLUSION: The circadian and sleep
      stage-specific effects on heart rate variability are clinically relevant and
      contribute to the understanding of the degree of cardiovascular vulnerability
      during sleep.

PMID- 24293768
TI  - Predictors of long-term adherence to continuous positive airway pressure therapy
      in patients with obstructive sleep apnea and cardiovascular disease in the SAVE
      study.
AB  - STUDY OBJECTIVES: To determine the clinical variables that best predict long-
      term continuous positive airway pressure (CPAP) adherence among patients with
      cardiovascular disease who have obstructive sleep apnea (OSA). DESIGN: 12-mo
      prospective within-trial observational study. SETTING: Centers in China,
      Australia, and New Zealand participating in the Sleep Apnea cardioVascular
      Endpoints (SAVE) study. PATIENTS: There were 275 patients age 45-70 y with
      cardiovascular disease (i.e., previously documented transient ischemic attack,
      stroke, or coronary artery disease) and OSA (4% oxygen desaturation index (ODI) >
      12) who were randomized into the CPAP arm of the SAVE trial prior to July 1,
      2010. METHODS: Age, sex, country of residence, type of cardiovascular disease,
      baseline ODI, severity of sleepiness, and Hospital Anxiety and Depression Scale
      (HADS) scores plus CPAP side effects and adherence at 1 mo were entered in
      univariate analyses in an attempt to identify factors predictive of CPAP
      adherence at 12 mo. Variables with P < 0.2 were then included in a multivariate
      analysis using a linear mixed model with sites as a random effect and 12-mo CPAP
      use as the dependent outcome variable. MEASUREMENTS AND RESULTS: CPAP adherence
      at 1, 6, and 12 mo was (mean +/- standard deviation) 4.4 +/- 2.0, 3.8 +/- 2.3,
      and 3.3 +/- 2.4 h/night, respectively. CPAP use at 1 mo (effect estimate +/-
      standard error, 0.65 +/- 0.07 per h increase, P < 0.001) and side effects at 1 mo
      (-0.24 +/- 0.092 per additional side effect, P = 0.009) were the only independent
      predictors of 12- mo CPAP adherence. CONCLUSION: Continuous positive airway
      pressure use in patients with coexisting cardiovascular disease and moderate to
      severe obstructive sleep apnea decreases significantly over 12 months. This
      decline can be predicted by early patient experiences with continuous positive
      airway pressure (i.e., adherence and side effects at 1 month), raising the
      possibility that intensive early interventions could improve long-term continuous
      positive airway pressure compliance in this patient population. CLINICAL TRIALS
      REGISTER: Clinical Trials, http://www.clinicaltrials.gov, NCT00738179.

PMID- 24293769
TI  - Children's sleep and autonomic function: low sleep quality has an impact on heart
      rate variability.
AB  - OBJECTIVES: Short sleep duration and poor sleep quality in children have been
      associated with concentration, problem behavior, and emotional instability, but
      recently also with disrupted autonomic nervous function, which predicts
      cardiovascular health. Heart rate variability (HRV) was used as noninvasive
      indicator of autonomic function to examine the influence of sleep. DESIGN: Cross
      sectional and longitudinal observational study on the effect of sleep on HRV.
      PARTICIPANTS: Belgian children (5-11 years) of the ChiBS study in 2010 (N = 334)
      and 2011 (N = 293). INTERVENTIONS: N/A. METHODS: Sleep duration was reported and
      in a subgroup sleep quality (efficiency, latency, awakenings) was measured with
      accelerometry. High-frequency (HF) power and autonomic balance (LF/HF) were
      calculated on supine 5-minute HRV measurements. Stress was measured by emotion
      and problem behavior questionnaires. Sleep duration and quality were used as HRV
      predictors in corrected cross-sectional and longitudinal regressions. Stress was
      tested as mediator (intermediate pathway) or moderator (interaction) in sleep-HRV
      associations. RESULTS: In both cross-sectional and longitudinal analyses, long
      sleep latency could predict lower HF (parasympathetic activity), while nocturnal
      awakenings, sleep latency, low sleep efficiency, and low corrected sleep duration
      were related to higher LF/HF (sympathetic/parasympathetic balance). Parental
      reported sleep duration was not associated with HRV. The significances remained
      after correction for stress. Stress was not a mediator, but a moderator
      (enhancer) in the relationship between sleep quality and HRV. CONCLUSIONS: Low
      sleep quality but not parent-reported low sleep duration leads to an unhealthier
      heart rate variability pattern (sympathetic over parasympathetic dominance). This
      stresses the importance of good sleep quality for cardiovascular health in
      children.

PMID- 24293770
TI  - A pro-inflammatory role for nuclear factor kappa B in childhood obstructive sleep
      apnea syndrome.
AB  - STUDY OBJECTIVES: Childhood obstructive sleep apnea syndrome (OSAS) is associated
      with an elevation of inflammatory markers such as C-reactive protein (CRP) that
      correlates with specific morbidities and subsides following intervention. In
      adults, OSAS is associated with activation of the transcription factor nuclear
      factor kappa B (NF-kB). We explored the mechanisms underlying NF-kB activation,
      based on the hypothesis that specific NF-kB signaling is activated in children
      with OSAS. DESIGN: Adenoid and tonsillar tissues from children with OSAS and
      matched controls were immunostained against NF-kB classical (p65 and p50) and
      alternative (RelB and p52) pathway subunits, and NF-kB-dependent cytokines:
      interleukin (IL)- 1alpha, IL-1beta, tumor necrosis factor-alpha, and IL-8). Serum
      CRP levels were measured in all subjects. NF-kB induction was evaluated by a
      luciferase-NF-kB reporter assay in L428 cells constitutively expressing NF-kB and
      in Jurkat cells with inducible NF-kB expression. p65 translocation to the
      nucleus, reflecting NF-kB activation, was measured in cells expressing
      fluorescent NF-kB-p65-GFP (green fluorescent protein). SETTING: Sleep research
      laboratory. PATIENTS OR PARTICIPANTS: Twenty-five children with OSAS and 24
      without OSAS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Higher expression of
      IL-1alpha and classical NF-kB subunits p65 and p50 was observed in adenoids and
      tonsils of children with OSAS. Patient serum induced NF-kB activity, as measured
      by a luciferase-NF-kB reporter assay and by induction of p65 nuclear
      translocation in cells permanently transfected with GFP-p65 plasmid. IL-1beta
      showed increased epithelial expression in OSAS tissues. CONCLUSIONS: Nuclear
      factor kappa B is locally and systemically activated in children with obstructive
      sleep apnea syndrome. This observation may motivate the search for new anti
      inflammatory strategies for controlling nuclear factor kappa B activation in
      obstructive sleep apnea syndrome.

PMID- 24293771
TI  - Alexithymia associated with nightmare distress in idiopathic REM sleep behavior
      disorder.
AB  - STUDY OBJECTIVES: Idiopathic REM sleep behavior disorder (iRBD) is characterized
      by atypical REM sleep motor activity, vivid dreams and nightmares, and dream
      enacting behaviors that can result in injuries to the patient and bed partner. It
      is also a known predictor of Parkinson disease (PD). Alexithymia has been
      associated with disturbances in sleep and dreaming (e.g., nightmares) and is a
      non-motor symptom of PD. We assessed alexithymia and disturbed dreaming in iRBD
      patients with the aim of determining if these two factors are elevated and
      interrelated among this population. DESIGN: Questionnaire study of clinically
      diagnosed patients. SETTING: Clinical sleep disorders center. PATIENTS OR
      PARTICIPANTS: Thirty-two iRBD patients and 30 healthy age- and sex-matched
      control participants. MEASUREMENTS AND RESULTS: Participants completed the 20
      item Toronto Alexithymia Scale (TAS-20), the Dream Questionnaire, and the Beck
      Depression Inventory. iRBD patients obtained higher TAS-20 total scores (62.16 +/
      13.90) than did controls (52.84 +/- 7.62; F 1,59 = 10.44, P < 0.01), even when
      controlling for depressive symptoms, and more frequently attained the suggested
      cutoff for alexithymia than did controls (P < 0.01). iRBD patients obtained
      higher scores on the Difficulty Identifying Feelings alexithymia subscale. For
      both iRBD and control groups, the Difficulty Indentifying Feelings subscale
      correlated positively with the Nightmare Distress scale of the Dream
      Questionnaire. CONCLUSIONS: Elevated alexithymia scores among idiopathic rapid
      eye movement sleep behavior disorder patients, and especially a difficulty in
      identifying feelings, parallels evidence of dysautonomia in this population. The
      higher incidence of distressing nightmares and the association of nightmares with
      alexithymia further extend similar findings for both clinical and non-clinical
      samples and suggest that an affect regulation disturbance may be common to the
      two sets of symptoms.

PMID- 24293772
TI  - Sleep disorders and increased risk of subsequent acute coronary syndrome in
      individuals without sleep apnea: a nationwide population-based cohort study.
AB  - OBJECTIVES: Studies investigating the relationship between nonapnea sleep
      disorders and the risk of acute coronary syndrome (ACS) are scant. This study
      evaluated whether the risk of ACS is associated with sleep disorders other than
      sleep apnea in Taiwan. METHODS: This longitudinal nationwide population-based
      cohort study investigated the incidence and risk of ACS in 49,099 cases of
      nonapnea sleep disorders newly diagnosed from January 1997 to December 2001. In
      total, 98,198 control participants without sleep disorders were randomly
      selected, frequency matched by age and sex from the general population. The
      follow-up period started from the date of entering the study cohort to the date
      of an ACS event, censoring, or December 31, 2010. We conducted Cox proportional
      hazard regression analysis to estimate the effects of nonapnea sleep disorders on
      ACS risk. RESULTS: The nonapnea sleep disorder cohort had an adjusted hazard
      ratio (HR; 95% confidence interval [CI] = 1.29-1.60) of subsequent ACS 1.43-fold
      higher than that of the cohort without sleep disorders. The highest crude effect
      of nonapnea sleep disorders on ACS incidence was detected among young adults.
      However, by adjusting for probable risk factors, the HR of ACS increased with
      age. Compared with women, men had an adjusted HR of 1.57 (95% CI = 1.42-1.75).
      Hypertension, diabetes mellitus (DM), and hyperlipidemia were also significant
      factors associated with the increased risk of ACS. CONCLUSION: This nationwide
      population-based cohort study provides evidence that patients with nonapnea sleep
      disorders are at higher risk of developing acute coronary syndrome, which
      increases with age.

PMID- 24293773
TI  - Are nocturnal breathing, sleep, and cognitive performance impaired at moderate
      altitude (1,630-2,590 m)?
AB  - STUDY OBJECTIVES: Newcomers at high altitude (> 3,000 m) experience periodic
      breathing, sleep disturbances, and impaired cognitive performance. Whether
      similar adverse effects occur at lower elevations is uncertain, although numerous
      lowlanders travel to moderate altitude for professional or recreational
      activities. We evaluated the hypothesis that nocturnal breathing, sleep, and
      cognitive performance of lowlanders are impaired at moderate altitude. DESIGN:
      Randomized crossover trial. SETTING: University hospital at 490 m, Swiss mountain
      villages at 1,630 m and 2,590 m. PARTICIPANTS: Fifty-one healthy men, median
      (quartiles) age 24 y (20-28 y), living below 800 m. INTERVENTIONS: Studies at
      Zurich (490 m) and during 4 consecutive days at 1,630 m and 2,590 m,
      respectively, 2 days each. The order of altitude exposure was randomized.
      Polysomnography, psychomotor vigilance tests (PVT), the number back test, several
      other tests of cognitive performance, and questionnaires were evaluated.
      MEASUREMENTS AND RESULTS: The median (quartiles) apnea-hypopnea index at 490 m
      was 4.6/h (2.3; 7.9), values at 1,630 and 2,590 m, day 1 and 2, respectively,
      were 7.0/h (4.1; 12.6), 5.4/h (3.5; 10.5), 13.1/h (6.7; 32.1), and 8.0/h (4.4;
      23.1); corresponding values of mean nocturnal oxygen saturation were 96% (95;
      96), 94% (93; 95), 94% (93; 95), 90% (89; 91), 91% (90; 92), P < 0.05 versus 490
      m, all instances. Slow wave sleep on the first night at 2,590 m was 21% (18; 25)
      versus 24% (20; 27) at 490 m (P < 0.05). Psychomotor vigilance and various other
      measures of cognitive performance did not change significantly. CONCLUSIONS:
      Healthy men acutely exposed during 4 days to hypoxemia at 1,630 m and 2,590 m
      reveal a considerable amount of periodic breathing and sleep disturbances.
      However, no significant effects on psychomotor reaction speed or cognitive
      performance were observed. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov:
      NCT01130948.

PMID- 24293774
TI  - A gonadotropin-releasing hormone agonist model demonstrates that nocturnal hot
      flashes interrupt objective sleep.
AB  - OBJECTIVES: Sleep interruption is often reported by women with hot flashes and
      night sweats (or vasomotor symptoms, VMS). Although women report that VMS awaken
      them, polysomnography (PSG) studies have not consistently supported this
      contention. DESIGN: We mimicked menopause using a gonadotropin-releasing hormone
      agonist (GnRHa) to investigate whether VMS increase awakenings and wake after
      sleep onset (WASO). VMS, serum estradiol, and at-home PSGs (two pretreatment, two
      posttreatment) were measured before and after 4 weeks on GnRHa. Regression models
      were used to determine the effect of increasing VMS frequency on awakenings and
      WASO, as measured objectively and subjectively. PARTICIPANTS: Twenty-nine healthy
      women (mean 27.3 y). SETTING: Academic medical center. INTERVENTIONS: Depot GnRHa
      (leuprolide 3.75-mg). RESULTS: Serum estradiol was rapidly and uniformly
      suppressed on GnRHa. Persistent VMS were reported by 69% of women. The number of
      nighttime VMS correlated directly with the degree of sleep disturbance. Each
      additional reported nighttime VMS was associated with a 62% increase from
      baseline in PSG-measured WASO (P = 0.007), a 3% increase in awakenings (P =
      0.05), and 6% increase in %N1 sleep (P = 0.02). Nighttime VMS were also
      associated with increased perceived WASO (312%; P = 0.02), awakenings (16%; P =
      0.007), Insomnia Severity Index (P = 0.03), and Pittsburgh Sleep Quality Index (P
      = 0.03) scores, and decreased perceived sleep efficiency (P = 0.01). Objectively
      recorded nighttime VMS correlated with PSG-measured WASO (rs = 0.45, P = 0.02).
      CONCLUSIONS: This menopause model demonstrates that nighttime vasomotor symptoms
      correlate with increased sleep fragmentation. These findings are consistent with
      a specific contribution of vasomotor symptoms to polysomnography-measured sleep
      interruption suggesting that nighttime vasomotor symptoms interrupt sleep in the
      setting of menopause.

PMID- 24293775
TI  - Dynamic circadian modulation in a biomathematical model for the effects of sleep
      and sleep loss on waking neurobehavioral performance.
AB  - Recent experimental observations and theoretical advances have indicated that the
      homeostatic equilibrium for sleep/wake regulation--and thereby sensitivity to
      neurobehavioral impairment from sleep loss--is modulated by prior sleep/wake
      history. This phenomenon was predicted by a biomathematical model developed to
      explain changes in neurobehavioral performance across days in laboratory studies
      of total sleep deprivation and sustained sleep restriction. The present paper
      focuses on the dynamics of neurobehavioral performance within days in this
      biomathematical model of fatigue. Without increasing the number of model
      parameters, the model was updated by incorporating time-dependence in the
      amplitude of the circadian modulation of performance. The updated model was
      calibrated using a large dataset from three laboratory experiments on psychomotor
      vigilance test (PVT) performance, under conditions of sleep loss and circadian
      misalignment; and validated using another large dataset from three different
      laboratory experiments. The time-dependence of circadian amplitude resulted in
      improved goodness-of-fit in night shift schedules, nap sleep scenarios, and
      recovery from prior sleep loss. The updated model predicts that the homeostatic
      equilibrium for sleep/wake regulation--and thus sensitivity to sleep loss-
      depends not only on the duration but also on the circadian timing of prior sleep.
      This novel theoretical insight has important implications for predicting operator
      alertness during work schedules involving circadian misalignment such as night
      shift work.

PMID- 24293776
TI  - The impact of circadian misalignment on athletic performance in professional
      football players.
AB  - OBJECTIVE: We hypothesized that professional football teams would perform better
      than anticipated during games occurring close to their circadian peak in
      performance. DESIGN: We reviewed the past 40 years of evening and daytime
      professional football games between west coast and east coast United States
      teams. In order to account for known factors influencing football game outcomes
      we compared the results to the point spread which addresses all significant
      differences between opposing teams for sports betting purposes. One sample t
      tests, Wilcoxon signed ranked tests, and linear regression were performed.
      Comparison to day game data was included as a control. SETTING: Academic medical
      center. PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: The results were strongly
      in favor of the west coast teams during evening games against east coast teams,
      with the west coast teams beating the point spread about twice as often (t =
      3.95, P < 0.0001) as east coast teams. For similar daytime game match-ups, we
      observed no such advantage. CONCLUSIONS: Sleep and circadian physiology have
      profound effects on human function including the performance of elite athletes.
      Professional football players playing close to the circadian peak in performance
      demonstrate a significant athletic advantage over those who are playing at other
      times. Application of this knowledge is likely to enhance human performance.

PMID- 24293778
TI  - Estimation and inference concerning ordered means in analysis of covariance
      models with interactions.
AB  - When interactions are identified in analysis of covariance models it becomes
      important to identify values of the covariates for which there are significant
      differences or, more generally, significant contrasts among the group mean
      responses. Inferential procedures that incorporate a priori order restrictions
      among the group mean responses would be expected to be superior to those that
      ignore this information. In this paper we focus on analysis of covariance models
      with pre-specified order restrictions on the mean response across the levels of a
      grouping variable when the grouping variable may interact with model covariates.
      In order for the restrictions to hold in the presence of interactions, it is
      necessary to impose the requirement that the restrictions hold over all levels of
      interacting categorical covariates and across pre-specified ranges of interacting
      continuous covariates. The parameter estimation procedure involves solving a
      quadratic programming minimization problem with a carefully specified constraint
      matrix. Simultaneous confidence intervals for treatment group contrasts and tests
      for equality of the ordered group mean responses are determined by exploiting
      previously unconnected literature. The proposed methods are motivated by a
      clinical trial of the dopamine agonist pramipexole for the treatment of early
      stage Parkinson's disease.

PMID- 24293779
TI  - A GEE Approach to Determine Sample Size for Pre- and Post-Intervention
      Experiments with Dropout.
AB  - Pre- and post-intervention experiments are widely used in medical and social
      behavioral studies, where each subject is supposed to contribute a pair of
      observations. In this paper we investigate sample size requirement for a scenario
      frequently encountered by practitioners: All enrolled subjects participate in the
      pre-intervention phase of study, but some of them will drop out due to various
      reasons, thus resulting in missing values in the post-intervention measurements.
      Traditional sample size calculation based on the McNemar's test could not
      accommodate missing data. Through the GEE approach, we derive a closed-form
      sample size formula that properly accounts for the impact of partial
      observations. We demonstrate that when there is no missing data, the proposed
      sample size estimate under the GEE approach is very close to that under the
      McNemar's test. When there is missing data, the proposed method can lead to
      substantial saving in sample size. Simulation studies and an example are
      presented.

PMID- 24293780
TI  - RIEMANN ZEROS AND THE INVERSE PHASE PROBLEM.
AB  - Finding a universal method of crystal structure solution and proving the Riemann
      hypothesis are two outstanding challenges in apparently unrelated fields. For
      centrosymmetric crystals however, a connection arises as the result of a
      statistical approach to the inverse phase problem. It is shown that parameters of
      the phase distribution are related to the non-trivial Riemann zeros by a Mellin
      transform.

PMID- 24293781
TI  - Skeletal Involvement of Brucella melitensis in Children: A Systematic Review.
AB  - Brucellosis is a protean disease and should be excluded in any febrile child with
      a constellation of symptoms such as fever, malaise, sweating, arthralgia, and
      joint swelling in endemic areas. Skeletal system involvement is the most common
      source of complaints in brucellosis. The frequency of skeletal involvement in
      children is 6.4% to 73.5%. There are some controversies regarding the most common
      sites of involvement: sacroiliac versus peripheral joints. In the vast majority
      of cases, peripheral joint involvement in pediatric brucellosis has a
      monoarticular pattern, although there is no agreement about the most commonly
      involved peripheral joint. In this systematic review, published articles that
      describe the bone involvement of Brucella melitensis, as the most prevalent kind
      of the microorganism in the region, in children are evaluated. 

PMID- 24293782
TI  - Efficacy of topical alpha ointment (containing natural henna) compared to topical
      hydrocortisone (1%) in the healing of radiation-induced dermatitis in patients
      with breast cancer: a randomized controlled clinical trial.
AB  - BACKGROUND: This two-arm, randomized clinical study aimed to compare efficacy
      between topical Alpha ointment and topical hydrocortisone cream (1%) in the
      healing of radiation-induced dermatitis in breast cancer patients. METHODS: The
      inclusion criteria comprised newly pathologically proven, locally advanced breast
      cancer (treated with modified radical mastectomy followed by sequential adjuvant
      treatments, including chest wall radiotherapy [45-50.4 Gy]) and grade 2 and/or 3
      chest wall dermatitis. The exclusion criteria were comprised of any underlying
      disease or medications interfering with the wound healing process, previous
      history of chest wall radiotherapy, and concurrent use of chemotherapy. Sixty
      eligible patients were randomly assigned to use either topical Alpha ointment
      (study arm, n=30) or topical hydrocortisone cream (1%) (control arm, n=30)
      immediately after receiving a total dose of 45-50 Gy chest wall radiotherapy.
      RESULTS: The mean radiation dose was 49.1 Gy in the control arm and 48.8 Gy in
      the study arm. The mean dermatitis area was 13.54 cm(2) in the control arm and
      17.02 cm(2) in the study arm. Topical Alpha ointment was more effective on the
      healing of radiation-induced dermatitis than was topical hydrocortisone cream
      (1%) (P=0.001). This effect was significant in the second week (P=0.007). In
      addition, Alpha ointment decreased the patients' complaints such as pain
      (P<0.001), pruritus (P=0.009), and discharge (P=0.010) effectively and
      meaningfully. CONCLUSION: Topical Alpha ointment was more effective on the
      healing of radiation-induced dermatitis than was topical hydrocortisone cream
      (1%) in our patients with breast cancer. TRIAL REGISTRATION NUMBERS:
      IRCT201206099979N1, ACTRN12612000837820.

PMID- 24293783
TI  - Cytogenetic findings of patients with acute lymphoblastic leukemia in fars
      province.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the sixth most common
      malignancy in Iran. Cytogenetic analysis of leukemic blasts plays an important
      role in classification and prognosis in ALL patients. The purpose of this study
      was to define the frequency of chromosomal abnormalities of ALL patients in
      adults and children in Fars province, Iran. METHODS: In this cross-sectional
      study, we evaluated karyotype results of bone marrow specimens in 168 Iranian
      patients with ALL (154 B-ALL and 14 T-ALL) in Fars Province using the
      conventional cytogenetic G-banding method. RESULTS: The frequency of cytogenetic
      abnormalities, including numerical and/or structural changes, was 61.7% and 53.8%
      in the B-ALL and T-ALL patients, respectively. Hyperdiploidy was the most common
      (32%) cytogenetic abnormality. Among structural abnormalities, the most common
      was t(9;22) in 11% of the patients. The children showed a higher incidence of
      hyperdiploidy and lower incidence of t(9;22) than adults (P<0.05). We found a
      lower incidence of recurrent abnormalities such as 11q23, t(1;19), and t(12;21)
      than those reported in previous studies. CONCLUSION: Normal karyotype was more
      frequent in our study. The frequencies of some cytogenetic abnormalities such as
      hyperdiploidy and t(9;22) in our study were comparable to those reported in the
      literature. The results of this study in Fars Province can be used as baseline
      information for treatment decision and research purposes in ALL patients. We
      recommend the use of advanced molecular techniques in the future to better
      elucidate cryptic cytogenetic abnormalities.

PMID- 24293784
TI  - Evaluation of factors influencing liver function test in on-pump coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Liver dysfunction during on-pump coronary artery bypass graft surgery
      (CABG) is a rare complication but is associated with significant morbidity and
      mortality. The ability to identify high-risk patients may be helpful in planning
      appropriate management strategies. We aimed to evaluate the factors influencing
      liver function tests during on-pump CABG. METHODS: In 146 patients scheduled for
      on-pump CABG, the liver function test was done preoperatively and on the first
      postoperative day. Some preoperative and intraoperative risk factors were checked
      and then the postoperative liver function tests were compared with the
      preoperative ones. Probable relationships between these changes and the
      preoperative and intraoperative risk factors were studied. RESULTS: A medical
      history of diabetes had a significant relationship with the changes in direct
      bilirubin. Preoperative central venous pressure had a significant relationship
      with the changes in aspartate aminotransferase and alanine aminotransferase. Use
      of intra-aortic balloon pump and duration of aortic cross-clamp were
      significantly related to the changes in the liver function tests except for
      alanine aminotransferase and alkaline phosphatase. CONCLUSION: It seems that the
      techniques for the reduction of cardiopulmonary bypass and aortic cross-clamp
      duration may be useful to protect liver function. We recommend that a larger
      population of patients be studied to confirm these findings.

PMID- 24293785
TI  - Hospital mortality associated with stroke in southern iran.
AB  - BACKGROUND: Unlike the western hemisphere, information about stroke epidemiology
      in southern Iran is scarce. The aim of this study was to determine the main
      epidemiological characteristics of patients with stroke and its mortality rate in
      southern Iran. METHODS: A retrospective, single-center, hospital-based
      longitudinal study was performed at Nemazee Hospital in Shiraz, Southern Iran.
      Patients with a diagnosis of hemorrhagic and ischemic strokes were identified
      based on the International Classification of Diseases, 9th and 10th editions, for
      the period between 2001 and 2010. Demographics including age, sex, area of
      residence, socioeconomic status, length of hospital stay, and discharge
      destinations were analyzed in association with mortality. RESULTS: 16351 patients
      with a mean age of 63.4 years (95% CI: 63.1, 63.6) were included in this
      analysis. Men were slightly predominant (53.6% vs. 46.4%). Forty-seven percent of
      the total sample was older than 65,17% were younger than 45, and 2.6% were
      children younger than 18. The mean hospital stay was 6.3 days (95% CI: 6.2, 6.4).
      Among all types of strokes, the overall hospital mortality was 20.5%. Multiple
      logistic regression revealed significantly higher in-hospital mortality in women
      and children (P<0.001) but not in patients with low socioeconomic status or from
      rural areas. During the study period, the mortality proportions increased from
      17.8% to 22.2%. CONCLUSION: In comparison to western countries, a larger
      proportion of our patients were young adults and the mortality rate was higher.

PMID- 24293786
TI  - Effect of Heparin Administration during Coronary Angiography on Vascular or
      Peripheral Complications: A Single-Blind Randomized Controlled Clinical Trial.
AB  - BACKGROUND: Coronary angiography consists of the selective injection of contrast
      agents in coronary arteries. Optimal strategy for heparin administration during
      coronary angiography has yet to be determined. We assessed the effect of heparin
      administration during coronary angiography on vascular, hemorrhagic, and ischemic
      complications. METHODS: Five hundred candiates for diagnostic coronary
      angiography (femoral approach) were randomly divided into case (intravenous
      Heparin [2000-3000 units]) and control (placebo) groups. Assessment included
      vascular complications like groin hematoma, retroperitoneal hematoma,
      pseudoaneurysm, active hemorrhage, cerebral ischemia, and clot formation in the
      catheter or the sheath during angiography. Information was obtained about the
      patients' age, sex, and hypertension and diabetes mellitus history. Patients with
      severe peripheral vascular disease, aortic stenosis, history of coagulopathy, and
      angiography over 30 minutes were excluded. RESULTS: Nine patients from each group
      were excluded. The remaining 482 patients included 285 (59.1%) men and 197
      (40.9%) women. In the case group (n=241), 7 (2.9%) patients experienced active
      hemorrhage at the site of angiographic puncture, 2 (0.83%) developed groin
      hematoma, and 8 (3.32%) experienced clot formation during angiography, while the
      corresponding figures for the control group (n=241) were 3 (1.24%), 2 (083%), and
      13 (5.39%), respectively. No significant differences were found in hemorrhagic,
      ischemic, and vascular complications between the two groups. CONCLUSION: Heparin
      administration during coronary angiography had no effect on clot formation as
      well as hemorrhagic, ischemic, and vascular complications in our patients. TRIAL
      REGISTRATION NUMBER: IRCT201202199080N1.

PMID- 24293787
TI  - Is Abdominal Muscle Activity Different from Lumbar Muscle Activity during Four
      Point Kneeling?
AB  - BACKGROUND: Stabilization exercises can improve the performance of trunk and back
      muscles, which are effective in the prevention and treatment of low back pain.
      The four-point kneeling exercise is one of the most common types of stabilization
      exercises. This quasi-experimental study aimed to evaluate and compare the level
      of activation between abdominal and lumbar muscles in the different stages of the
      four-point kneeling exercise. METHODS: The present study was conducted on 30
      healthy women between 20 and 30 years old. Muscle activity was recorded
      bilaterally from transversus abdominis, internal oblique, and multifidus muscles
      with an electromyography (EMG) device during the different stages of the four
      point kneeling exercise. All the collected EMG data were normalized to the
      percentage of maximum voluntary isometric contraction. The repeated measures
      ANOVA and paired t-test were used for the statistical analysis of the data.
      RESULTS: A comparison between mean muscle activation in right arm extension and
      left leg extension showed that left internal oblique and left transverse
      abdominis muscles produced greater activation during left leg extension (P<0.05).
      The comparison of mean muscle activation between right arm extension and the bird
      dog position showed that, except for the right internal oblique, all the muscles
      produced higher activation in the bird-dog stage (P<0.05). In comparison to the
      bird-dog stage, the left multifidus showed high activation during left leg
      extension (P<0.05). CONCLUSION: The results of this study showed that the
      activity of all the above-mentioned muscles during quadruped exercise can provide
      stability, coordination, and smoothness of movements.

PMID- 24293788
TI  - Inactivation of Gram-Negative Bacteria by Low-Pressure RF Remote Plasma Excited
      in N2-O2 Mixture and SF6 Gases.
AB  - The role of low-pressure RF plasma in the inactivation of Escherichia coli O157,
      Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter sakazakii using N2-O2
      and SF6 gases was assessed. 1*10(9) colony-forming units (CFUs) of each bacterial
      isolate were placed on three polymer foils. The effects of pressure, power,
      distance from the source, and exposure time to plasma gases were optimized. The
      best conditions to inactivate the four bacteria were a 91%N2-9%O2 mixture and a
      30-minute exposure time. SF6 gas was more efficient for all the tested isolates
      in as much as the treatment time was reduced to only three minutes. Therefore,
      low-pressure plasma could be used to sterilize heat and/or moisture-sensitive
      medical instruments. 

PMID- 24293789
TI  - Successful Vaginal Delivery despite a Huge Ovarian Mucinous Cystadenoma
      Complicating Pregnancy: A Case Report.
AB  - A 22-year-old patient with 9 months of amenorrhea and a huge abdominal swelling
      was admitted to our institution with an ultrasonography report of a
      multiloculated cystic space-occupying lesion, almost taking up the whole abdomen
      (probably of ovarian origin), along with a single live intrauterine fetus. She
      delivered vaginally a boy baby within 4 hours of admission without any maternal
      complication, but the baby had features of intrauterine growth restriction along
      with low birth weight. On the 8(th) postpartum day, the multiloculated cystic
      mass, which arose from the right ovary and weighed about 11 kg, was removed via
      laparotomy. A mucinous cystadenoma with no malignant cells in peritoneal washing
      was detected in histopathology examination. This report describes a rare case of
      a successful vaginal delivery despite a huge cystadenoma of the right ovary
      complicating the pregnancy. 

PMID- 24293790
TI  - Co-incidence of acute appendicitis and appendiceal transection after blunt
      abdominal trauma: a case report.
AB  - A 13-year-old boy with a history of bicycle handlebar injury to the left side of
      his abdomen was brought to the Emergency Department of our center. On admission,
      his vital signs were stable and abdominal examination revealed ecchymosis and
      tenderness of the injured areas. Mild to moderate free fluid and two small foci
      of free air in the anterior aspect of the abdomen, in favor of pneumoperitoneum,
      were detected in abdominopelvic sonography and CT-scan, respectively. In less
      than 6 hours, the patient developed generalized peritonitis. Therefore,
      exploratory laparotomy was promptly performed, which revealed appendiceal
      transection and rupture of the small bowel mesentery. Appendectomy and small
      bowel mesoplasty were done, with pathological diagnosis of acute appendicitis and
      periappendicitis. After surgery, the patient had a non-complicated hospital
      course. This rare case highlights the significance of the early management of
      appendiceal traumatic injuries in order to prevent further complicated events,
      especially in patients who are much more exposed to this risk due to their
      traumatic background. 

PMID- 24293791
TI  - Methamphetamine intoxication in emergency departments of hospitals in iran:
      implications for treatment.

PMID- 24293792
TI  - Effect of Low versus Moderate Dose of Clofibrate on Serum Bilirubin in Healthy
      Term Neonates with Indirect Hyperbilirubinemia.

PMID- 24293793
TI  - Multivariate meta-analysis: a method to summarize non-linear associations.
AB  - Multivariate meta-analysis represents a promising statistical tool in several
      research areas. Here, we provide a brief overview of the application of this
      methodology to combining complex multi-parameterized relationships, such as non
      linear or delayed associations, in multi-site studies. The discussion focuses on
      the advantages over simpler univariate methods, estimation and computational
      issues and directions for further research.

PMID- 24293794
TI  - Solvent induced phenomena in a dendronized linear polymer.
AB  - The properties of a dendronized linear polymer (DP) in dilute solutions depending
      on solvent quality and temperature are described. The polymer has a contour
      length of Lc = 1,060 nm. The sample of the fourth generation (PG4) was analyzed
      in the thermodynamically good solvents dioxane, chloroform, and methanol. The
      wormlike macromolecule has a persistence length lp = 7 nm in dioxane and a cross
      section radius determined by small angle X-ray scattering (SAXS) of Rc (SAXS) =
      2.8 nm. The bulk density of PG4 determined by SAXS was compared with solution
      density. Evidence for substantial swelling of the cross-section was found.
      Toluene acts as a thermodynamically poor solvent (theta solvent). Above the theta
      temperature Ttheta , a strong temperature dependence of the size and the Young's
      modulus E was observed. Following Odijk, E/kBT ~1 was found. Below Ttheta , a
      regime characterized by unswelling of the wormlike chains was observed. The
      results suggest that DPs can be described as soft colloid filaments, which are
      subject to commonly observed interactions in colloidal systems. A phase diagram
      indicates a regime below Ttheta in which fluctuations of osmotic pressure inside
      the filaments result in periodic undulation of the chains. In summary,
      introducing a dense dendritic shell around the backbone converts conventional
      polymers into molecular colloids. Figure?

PMID- 24293796
TI  - The service component of interventional radiology.

PMID- 24293795
TI  - Physiochemical properties and kinetics of glucoamylase produced from deoxy-d
      glucose resistant mutant of Aspergillus niger for soluble starch hydrolysis.
AB  - Glucoamylases (GAs) from a wild and a deoxy-d-glucose-resistant mutant of a
      locally isolated Aspergillus niger were purified to apparent homogeneity. The
      subunit molecular mass estimated by SDS-PAGE was 93 kDa for both strains, while
      the molecular masses determined by MALDI-TOF for wild and mutant GAs were 72.876
      and 72.063 kDa, respectively. The monomeric nature of the enzymes was confirmed
      through activity staining. Significant improvement was observed in the kinetic
      properties of the mutant GA relative to the wild type enzyme. Kinetic constants
      of starch hydrolysis for A. niger parent and mutant GAs calculated on the basis
      of molecular masses determined through MALDI-TOF were as follows: kcat = 343 and
      727 s-1, Km = 0.25 and 0.16 mg mL-1, kcat/Km (specificity constant) = 1374 and
      4510 mg mL-1 s-1, respectively. Thermodynamic parameters for soluble starch
      hydrolysis also suggested that mutant GA was more efficient compared to the
      parent enzyme.

PMID- 24293797
TI  - Chest drainage.
AB  - Infectious, traumatic, or neoplastic processes in the chest often result in fluid
      collections within the pleural, parenchymal, or mediastinal spaces. The same
      fundamental principles that guide drainages of the abdomen can be applied to the
      chest. This review discusses various pathologic conditions of the thorax that can
      result in the abnormal accumulation of fluid or air, and their management using
      image-guided methods. 

PMID- 24293798
TI  - Approaches to the difficult drainage and biopsy.
AB  - Percutaneous abscess drainage and percutaneous biopsy are effective and widely
      used techniques in the diagnosis and treatment of patients with abdominal or
      pelvic abscesses and lesions. Some abscesses and lesions can initially appear
      unsuitable for percutaneous access for a variety of reasons. This article reviews
      the circumstances in which collections or lesions may appear undrainable or
      inaccessible to percutaneous biopsy, and it describes techniques for overcoming
      these circumstances. 

PMID- 24293799
TI  - Use of fibrinolytics in abdominal and pleural collections.
AB  - Fluid collections that are incompletely drained despite adequate catheter
      position, size, and number represent a minority of abscesses but a source of
      great frustration for patients, surgeons, and interventional radiologists.
      Drainage of such complex collections is known to be more effective with the
      adjunctive use of intracavitary fibrinolytic agents instilled via the drainage
      catheter. In this review article, we discuss the role of fibrinolytics
      specifically tissue plasminogen activator as explored by interventional
      radiologists in enhancing effective drainage of these complex abdominal and
      pelvic collections as well as complex pleural collections. 

PMID- 24293800
TI  - Musculoskeletal aspiration procedures.
AB  - With advances in imaging technology, there has been a significant increase in the
      number and range of interventional musculoskeletal image-guided procedures. One
      of the most commonly performed image-guided musculoskeletal interventions is the
      diagnostic and therapeutic percutaneous aspiration and drainage of multiple types
      of intra-articular, juxta-articular, and intramuscular pathologic fluid
      collections. These procedures may be performed under fluoroscopic, ultrasound,
      computed tomography, or even magnetic resonance guidance depending on the
      location to be accessed, type of pathology, patient characteristics, and operator
      preference. Musculoskeletal image-guided aspiration and drainage procedures are
      minimally invasive and generally very safe while offering valuable diagnostic
      information as well as therapeutic benefit. This article focuses on the
      appropriate indications, contraindications, and general technique for accessing
      the major joints via imaging guidance. For each joint, we discuss pertinent
      anatomy, appropriate imaging modalities, and preferred approaches to gaining
      intra-articular access. Additionally, the article discusses some of the more
      frequently encountered juxta-articular and intramuscular fluid collections that
      can be accessed and aspirated via percutaneous intervention, with mention of the
      importance of recognizing extremity sarcomas that can mimic these benign
      collections. 

PMID- 24293802
TI  - Percutaneous sclerotherapy of cystic lesions.
AB  - With modern cross-sectional imaging techniques, cystic lesions are very common
      and usually incidental findings, especially if small. However, when cysts
      enlarge, become infected, bleed, or undergo torsion, they can be symptomatic, and
      percutaneous drainage can be effective in the management. When cysts recur after
      aspiration, which is often the case for hepatic and renal cysts, cyst sclerosis
      or surgical unroofing may be required. This article describes the indications for
      and technical aspects of percutaneous sclerotherapy of cystic lesions of multiple
      organ systems. 

PMID- 24293801
TI  - Percutaneous drainage of abdominal and pelvic abscesses in children.
AB  - It has only been in the last several decades that abscesses within deep
      compartments, particularly within the abdomen and pelvis, have become safely
      accessible with imaging guidance. Since that time, percutaneous abscess drainage
      has become the standard of care in children. We review the clinical features,
      diagnosis, and image-guided management of abdominal and pelvic abscesses in
      children. 

PMID- 24293803
TI  - Image-guided percutaneous splenic biopsy and drainage.
AB  - Percutaneous splenic biopsy and drainage are relatively safe and accurate
      procedures. The risk of major complication (1.3%) following percutaneous splenic
      biopsy does not exceed that of other solid intra-abdominal organ biopsies, and it
      has less morbidity and mortality than splenectomy. Both computed tomography and
      ultrasound can be used to provide image guidance for biopsy and drainage. The
      safety profile of fine-needle aspiration cytology is better than core needle
      biopsy, but core biopsy has superior diagnostic accuracy. 

PMID- 24293804
TI  - Intra-abdominal abscess drainage: interval to surgery.
AB  - Placement of percutaneous drainage catheters has become first-line therapy in the
      treatment of patients with intra-abdominal abscesses. Catheters can be used to
      avoid surgical intervention or to improve surgical outcomes. This article
      discusses the current evidence describing the optimal interval between
      percutaneous drainage procedures and surgery, focusing on patients with Crohn's
      disease, appendicitis, and diverticulitis. 

PMID- 24293805
TI  - The role of imaging-guided percutaneous procedures in the multidisciplinary
      approach to treatment of pancreatic fluid collections.
AB  - Pancreatic fluid collections include a wide range of entities such as cystic
      neoplasms, both benign and malignant; vascular pathology such as pseudoaneurysms
      and hematomas; and a host of other entities such as pseudocysts, seromas,
      abscesses, and bilomas. The distinction between these entities requires
      correlating an often complex and overlapping clinical presentation with findings
      on imaging studies, typically computed tomography, magnetic resonance imaging,
      and ultrasound. As complex as the diagnostic work-up may be, the treatment of
      pancreatic collections poses its own set of challenges and often requires a
      multidisciplinary collaboration among interventional radiologists, surgeons, and
      gastroenterologists. The best treatment algorithm is determined by careful review
      of radiologic imaging studies combined with endoscopic retrograde
      cholangiopancreatography to apply therapies such as surgical resection; drainage
      or debridement; endoscopic ultrasound-guided drainage; aspiration or biopsy; and
      imaging-guided percutaneous drainage, aspiration, or biopsy. This article focuses
      on the diagnosis and multidisciplinary management of pancreatic fluid collections
      such as abscesses, pseudocysts, and necrosis. 

PMID- 24293806
TI  - Updates in percutaneous lung biopsy: new indications, techniques and
      controversies.
AB  - The objective of percutaneous chest biopsy is to consistently reach the amount of
      tissue required to meet or exceed published diagnostic accuracy rates. Many
      recent publications have reevaluated the subject of chest biopsy to assess
      borderline or controversial indications such as very small lesions, ground-glass
      opacities, and cases with a past nondiagnostic percutaneous biopsy. In addition,
      publications have reviewed sample adequacy for the accurate determination of
      molecular markers. These new indications promise to expand the numbers of biopsy
      procedures performed by radiologists. This article discusses the current role of
      image-guided percutaneous lung biopsies in the management of patients with
      pulmonary malignancies. 

PMID- 24293807
TI  - Abscess drainage.

PMID- 24293808
TI  - Error by distraction.

PMID- 24293809
TI  - Molecular imaging with surface-enhanced Raman spectroscopy nanoparticle
      reporters.
AB  - Molecular imaging scans cellular and molecular targets in living subjects through
      the introduction of imaging agents that bind to these targets and report their
      presence through a measurable signal. The picomolar sensitivity, signal
      stability, and high multiplexing capacity of Raman spectroscopy satisfies
      important needs within the field of molecular imaging, and several groups now
      utilize Raman and surface-enhanced Raman spectroscopy to image molecular targets
      in small animal models of human disease. This article details the role of Raman
      spectroscopy in molecular imaging, describes some substrates and imaging agents
      used in animal models, and illustrates some examples.

PMID- 24293810
TI  - The economic value of Quebec's water fluoridation program.
AB  - AIM: Dental caries is a major public health problem worldwide, with very
      significant deleterious consequences for many people. The available data are
      alarming in Canada and the province of Quebec. The water fluoridation program has
      been shown to be the most effective means of preventing caries and reducing oral
      health inequalities. This article analyzes the cost-effectiveness of Quebec's
      water fluoridation program to provide decision-makers with economic information
      for assessing its usefulness. METHODS: An approach adapted from economic
      evaluation was used to: (1) build a logic model for Quebec's water fluoridation
      program; (2) determine its implementation cost; and (3) analyze its cost
      effectiveness. Documentary analysis was used to build the logic model. Program
      cost was calculated using data from 13 municipalities that adopted fluoridation
      between 2002 and 2010 and two that received only infrastructure grants. Other
      sources were used to collect demographic data and calculate costs for caries
      treatment including costs associated with travel and lost productivity. RESULTS:
      The analyses showed the water fluoridation program was cost-effective even with a
      conservatively estimated 1 % reduction in dental caries. The benefit-cost ratio
      indicated that, at an expected average effectiveness of 30 % caries reduction,
      one dollar invested in the program saved $71.05-$82.83 per Quebec's inhabitant in
      dental costs (in 2010) or more than $560 million for the State and taxpayers.
      CONCLUSION: The results showed that the drinking-water fluoridation program
      produced substantial savings. Public health decision-makers could develop
      economic arguments to support wide deployment of this population-based
      intervention whose efficacy and safety have been demonstrated and acknowledged.

PMID- 24293811
TI  - Recent Advances in Development of DNA Vaccines Against Hepatitis C virus.
AB  - Hepatitis C is one of the foremost challenging diseases all over the world. No
      vaccine has been developed, yet against Hepatitis C virus (HCV). This is partly
      due to the high mutation rate in the HCV genome, which generates new genotypes
      and sub genotypes. A mass of efforts have been devoted for the development of an
      efficient vaccine against HCV. DNA Vaccines, an emerging field of Vaccinology,
      grasp strong potential to be the most reliable and efficient mode of vaccination
      in the future. This technology is under investigation currently. Incredibly
      diverse approaches have been applied as an endeavor to develop a potent DNA
      vaccine against HCV. The HCV structural genes and the virus like particles have
      been attempted and so far the results are quite promising in the Lab animals. As
      there is no proper animal model for HCV infection except chimpanzees, it is very
      difficult to articulate whether these vaccines will also be pertinent in humans
      or not. This review will focus on different approaches being used for the
      development of DNA vaccines, the major tribulations in designing a DNA vaccine
      against HCV as well as the future prospects for the improvement of under trials
      DNA vaccines developed against HCV. 

PMID- 24293812
TI  - Adaptations of a competitive enzyme-linked immunosorbent assays for the detection
      of antibodies to influenza a virus in horse sera for use in wild aquatic birds.
AB  - We applied a competitive enzyme-linked immunosorbent assay for the detection of
      antibodies for influenza A in equine sera to their detection in sera from wild
      aquatic birds. Suboptimal results were obtained for the optical density (OD) of
      the monoclonal antibody (MAb) control and reproducibility between duplicate
      analyses in the initial assessment. It was therefore necessary to modify the
      assay to deliver increased reliability and reproducibility while maintaining
      adequate sensitivity. We optimized reagent concentrations to obtain optimal OD
      values (close to 2) for the monoclonal antibody control and used 2, 2'-Azino-bis:
      3-Benzthiazoline-6-Sulphonic Acid as an alternative chromogen to potentially
      reduce variability in duplicate analyses. The original assay was compared with
      the optimized versions, with and without post coating, for the detection of avian
      influenza viral antibodies in 240 sera obtained from wild plumed whistling ducks.
      A separate analytical sensitivity study on diluted positive field sera of plumed
      whistling ducks and a test of antigen stability after post coating were also
      performed. Some quantitative differences were detected between the original and
      modified assays. The original assay recorded higher percentage inhibition results
      which were potentially indicative of increased sensitivity. However, when reagent
      concentrations were increased in the original assay to the same levels as used in
      the modified versions, there were no quantitative differences for practical
      purposes. The original assay produced a median (OD) value of 0.81 for the (MAb)
      controls that is at the limit of acceptability. By contrast, the modified assays
      always produced acceptable optical density values for MAb controls. Our overall
      results indicated the modified assays were potentially more reliable (OD values
      close to 2), and of adequate sensitivity compared to the original assay in the
      detection of avian influenza viral antibodies in wild bird sera. Although further
      optimization of antigen and MAb concentrations should also be considered to
      increase the sensitivity of a modified assay, while maintaining acceptable
      optical density values for the MAb control. Post coating had a minimal
      quantitative effect on the results and stabilized the plates for 214 days. We
      therefore recommend the incorporation of post coating. 

PMID- 24293813
TI  - Higher Immunological Protection of Pandemic 2009 H1N1 Influenza Live Virus
      Infection than Split Vaccine Against the Homologous Virus for Long Term
      Immunization in Ferret.
AB  - The study was to evaluate the long term immunological efficacy of pandemic 2009
      H1N1 influenza live virus infection and split vaccine against the homologous
      virus challenge in ferrets. Antibodies in ferrets were monitored by
      haemagglutination inhibition (HI) assay for 200 days, the HI titers of both
      infected-only and vaccinated plus infected ferrets could maintain a high level
      for at least 182 days, without significant difference between the two infected
      groups. While one-dose and two-dose vaccinated ferrets could last a moderate
      antibody titers for 81 days, with its peak value at day 7 post immunization.
      After the virus challenge at day 207, the two groups of vaccinated ferrets shed
      virus for longer time than the two infected groups, while the latter two groups
      basically did not shed any virus particles. Furthermore, the vaccinated and
      infected ferrets which were sacrificed at day 211 exerted moderate immune
      protection against the challenge by alleviating clinical signs and lung lesion
      without obvious difference between groups. These data supported that both one
      dose and two-dose vaccination of 2009 influenza A (H1N1) split vaccine conferred
      a moderate protection against challenge after 207 days, and there was no
      significant difference between the two groups. Either the infected only or
      vaccinated plus infected ones exerted more effective protective immune than one
      dose and two-dose vaccination against the challenge, especially in preventing
      virus shedding, and vaccination primed before infection had no additional
      efficacy. 

PMID- 24293814
TI  - Functional Characterization of Interferon Regulation Element of Hepatitis B virus
      Genome In Vivo.
AB  - The roles of interferon regulatory element (IRE) in Hepatitis B virus (HBV)
      genome on inhibitory effect of interferon against HBV are controversial in vitro.
      This study aimed to determine the functional characterization of HBV-IRE sequence
      in vivo. Wild-type or IRE-mutant HBV replication-competent mice were firstly
      established, and mice were subquently treated with polyinosinic-polytidylin acid
      (polyI.C) or phosphate-buffered saline via intraperitoneal. Results showed that
      PolyI.C inhibited viral replication, and increased the level of 2',5'
      oligoadenylate synthase mRNA transcripts, a marker of INF-alpha/beta induction.
      Between wild-type and IRE-mutant HBV replication-competent mice, the levels of
      HBV-RNA and HBV-DNA replication intermediates were similar. After PolyI.C
      treatment, the decreasing of HBV-RNA was similar between two groups, but HBV-DNA
      replication intermediates decreased significantly less in IRE-mutant than wild
      type HBV replication-competent mice. These findings suggested that IRE mutant
      reduced the inhibitory effect of interferon on HBV replication, which played a
      role in antiviral effect of interferon against HBV. 

PMID- 24293815
TI  - The Distribution of CCR2-64I, SDF1-3'A and MCP1-2518 G/A Genes Polymorphism in a
      Specific High Risk Group from the Northeastern States West Bengal, and Gorkha
      Population in India.
AB  - We studied the prevalence and effects of host genetic polymorphisms for the three
      AIDS restriction genes (ARGs) namely CCR2-64I, SDF1-3'A and MCP1-2518 G/A for HIV
      infection and progression to AIDS using PCR-RFLP analysis on a total of 568 HIV
      seronegative serum samples collected from a specific high risk and young
      population hailing from the seven Northeastern states of India (n = 346), West
      Bengal (n = 96) and Gorkha population (n = 101). In addition, 181 HIV
      seropositive cases of which 92 inpatient cases in a large tertiary care hospital
      located at Kolkata were included in the study. HIV prevalence in our study group
      was 0.52 %. Four cases seroconverted, 25 cases progressed to AIDS and 05 died
      during the follow up period of 41 months. The genotype percentage of CCR2-64I,
      SDF1-3'A and MCP1-2518 G/A in the Northeastern states were 18.5, 40.3 and 54 %
      respectively in the seronegative population. Allele frequencies for SDF1-3'A in
      Northeastern states were significantly higher as compared to the Gorkha (21 %)
      and the North Indian population (24 %). Relative Hazard values were more than 0.9
      for progression to AIDS and death. Kaplan-Meier survival analysis using Cox
      proportional regression model did not reveal any significant survival benefit (p
      value <0.05) for any of the 3 ARGs individually or in combination either to
      seroconversion or disease progression. This is the first study on host genetic
      polymorphism amongst the Eastern, Northeastern and Gorkha regions in India. We
      are also the first to report the MCP1-2518 G/A polymorphism in India that is
      known to increase the rate of neuropsychological impairment (NPI) in AIDS
      patients. 

PMID- 24293817
TI  - A colorimetric-based accurate method for the determination of enterovirus 71
      titer.
AB  - The 50 % tissue culture infectious dose (TCID50) is still one of the most
      commonly used techniques for estimating virus titers. However, the traditional
      TCID50 assay is time consuming, susceptible to subjective errors and generates
      only quantal data. Here, we describe a colorimetric-based approach for the
      titration of Enterovirus 71 (EV71) using a modified method for making virus
      dilutions. In summary, the titration of EV71 using MTT or MTS staining with a
      modified virus dilution method decreased the time of the assay and eliminated the
      subjectivity of observational results, improving accuracy, reproducibility and
      reliability of virus titration, in comparison with the conventional TCID50
      approach (p < 0.01). In addition, the results provided evidence that there was
      better correlation between a plaquing assay and our approach when compared to the
      traditional TCID50 approach. This increased accuracy also improved the ability to
      predict the number of virus plaque forming units present in a solution. These
      improvements could be of use for any virological experimentation, where a quick
      accurate titration of a virus capable of causing cell destruction is required or
      a sensible estimation of the number of viral plaques based on TCID50 of a virus
      is desired. 

PMID- 24293816
TI  - Enteroviral central nervous system infections in children of the region of
      monastir, Tunisia: diagnosis, laboratory findings of cerebrospinal fluid and
      clinical manifestations.
AB  - Human enteroviruses (HEV) are one of the major causes of central nervous system
      (CNS) infections in pediatrics. A prospective study was conducted to assess the
      epidemiological, clinical, and laboratory characteristics of enterovirus (EV)
      infections of the CNS in children under 15-years-old, suspected of having viral
      CNS infections and admitted to the Pediatric Department of Monastir University
      Hospital, Tunisia. Enteroviral RNA was detected by 5' NCR nested RT-PCR assay in
      33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples
      (10 %) were EV positive in cell culture. EV-positive patients were clustered
      according to their clinical manifestations, predominantly diagnosed as aseptic
      meningitis (65 %) and meningoencephalitis (20 %). Fever, headache, vomiting, and
      neck stiffness were the most pronounced symptoms. Pleocytosis with the
      predominance of lymphocytes was observed in 60 % of EV positive specimens.
      Although patients suffering from EV infections were encountered throughout the
      year, most occurred during spring and summer months. Using VP1-2A nested RT-PCR
      and sequence analysis, three of the 20 positive HEV were identified as Echovirus
      (E)-9. This is the first report of a cluster of aseptic meningitis cases caused
      by E-9 in Monastir. 

PMID- 24293818
TI  - Comparative proteomics analysis of mice lymphocytes in early stages of infection
      by different strains of rabies virus.
AB  - The CNS immune response to rabies virus has been shown to be influenced by
      virulence of the virus strains. There is no comprehensive report of the
      peripheral immune response against different strains of rabies virus. In this
      report we used a comparative proteome analysis to find the early events in the
      spleen lymphocytes of mice infected by a street strain and an attenuated strain
      of the rabies virus. Differentially expressed proteins were identified which play
      important biological roles such as T and B lymphocyte activation (coronin 1),
      antiviral activity (peroxiredoxin 1), and cytoskeletal reorganization (cofilin
      1). These results could be strong hints of early divergence on peripheral immune
      response under influence of viral strain and their pathogenicity. 

PMID- 24293819
TI  - Development of monoclonal antibodies suitable for rabies virus antibody and
      antigen detection.
AB  - The control of an infectious viral disease as rabies is made easier by rapid and
      accurate diagnosis. Successful rabies prophylaxis is dependent upon the active
      immunization with vaccine along with passive administration of rabies virus
      neutralizing antibodies which together clear the virus before widespread
      infection of central nervous system occurs. The present study aimed at the
      development of monoclonal antibodies (MAbs) suitable for rabies virus antibody
      and antigen detection. For the production of rabies specific MAbs, immunization
      of Swiss albino mice with a commercially available vaccine was done and
      Polyethylene glycol mediated fusion of spleenocytes with myeloma cells was
      performed. The positive clones were selected on the basis of distinct reactivity
      by cell Enzyme linked immunosorbent assay and fluorescence in Indirect
      Fluorescent antibody test. The positive clones obtained were subjected to single
      cell cloning by limiting dilution method. The reactive clones were further
      titrated and employed for virus titration and virus neutralization. The
      neutralizing activity was evaluated using Fluorescence Activated Cell Sorter
      technique. Three MAb clones showed a distinct percent inhibition in the presence
      of positive serum. One of the MAb clone No. 5C3 was relatively more specific in
      detecting rabies antibodies and also found suitable for competitive ELISA to
      assess the antibody level in vaccinated subjects. 

PMID- 24293820
TI  - Expression of Foot-and-Mouth Disease Virus Non-Structural Protein, 3D in Insect
      Cells and its Application in Detection of Anti-FMDV Antibodies.
AB  - Non-structural proteins (NSPs) based diagnostics are useful for large-scale sero
      surveillance of foot-and-mouth disease (FMD) and to monitor viral activity as a
      follow up to the vaccination campaign in FMD endemic countries like India which
      aim at disease control through vaccination. These diagnostics are also handy in
      the serology of import/export of cloven-footed animals. In the present study, non
      structural protein RNA polymerase (3D gene) of FMD virus (FMDV) was expressed
      using baculovirus expression system. Protein expression was analyzed by SDS-PAGE
      and confirmed by its immuno-reactivity with serum from a FMDV infected bovine, in
      the western blot. Recombinant 3D protein was purified and evaluated in the
      indirect ELISA with 1072 cattle serum samples. Diagnostic sensitivity and
      specificity of the assay were found to be 92 and 100 %, respectively, when tested
      with cattle sera of known FMD status. The 3D based ELISA developed here is useful
      for screening the animals as an adjunct to other NSP based diagnostics available
      for routine serosurveillance of FMD. 

PMID- 24293821
TI  - Transcript Analysis of White spot syndrome virus Latency and Phagocytosis
      Activating Protein Genes in Infected Shrimp (Penaeus monodon).
AB  - Viral latency has been recently observed to be associated with White spot
      syndrome virus (WSSV) infection in shrimp. In the present study, shrimp samples
      (Penaeus monodon) surviving WSSV infection were examined for presence of WSSV in
      latent phase. Virus latency was observed in shrimp which were either
      experimentally challenged with WSSV and survived the infection or those which
      survived the natural infection. Three viral transcripts (ORFs 427, 151, 366)
      associated with latency were analyzed by real-time PCR. The shrimp surviving the
      natural WSSV infection on estimation with RT-PCR were found to have low grade of
      WSSV infection (less than 56 copies of WSSV). All the shrimp samples were RT-PCR
      negative for structural protein genes of WSSV, VP24 and VP28, indicating that
      these samples were harboring latent phase virus. RT-PCR of all the shrimp samples
      which survived WSSV infection revealed amplification of phagocytosis activating
      protein (PAP) gene (435 bp) with higher gene expression levels in experimentally
      challenged shrimp when compared to naturally infected shrimp. The expression of
      PAP in WSSV infected shrimp samples indicates its possible role in host response
      for resistance against WSSV infection. PAP was cloned and expressed as
      recombinant protein for protection studies. Shrimp were injected with three doses
      (5, 15 and 20 MUg g(-1) body weight) of recombinant PAP. Relative percent
      survival of 10 % was observed in shrimp immunized with the dose of 15 MUg g(-1)
      body weight of recombinant PAP. The expression of both WSSV latency associated
      and PAP genes obtained from shrimp surviving the WSSV infection, indicates the
      possible role of these genes in host-pathogen interaction. 

PMID- 24293822
TI  - Main Factors Influencing the Efficient Propagation of Virulent or Attenuated
      Strains of Japanese encephalitis virus in BHK-21 Cells.
AB  - Japanese encephalitis virus (JEV) causes severe viral encephalitis in humans and
      some other mammalian animals. Highly efficient culture of the virus is critical
      for antigen preparation, vaccine production and other basic researches. We have
      investigated the influence of a number of variables such as the strain virulence,
      the state of the host cells, medium composition, infection method and others on
      the proliferation of distinct JEV strains in BHK-21 cells. The results showed
      that two distinct strategies are needed for the propagation of virulent or
      attenuated JEV strains. The most critical variables were the method of infection,
      and especially the density of the host cell. Our studies indicate the general
      approaches to the in vitro culture of other JEV strains using BHK-21 cell line. 

PMID- 24293823
TI  - Diversity of Hepatitis C virus in Southern India Based on 5'UTR Sequence.
AB  - Hepatitis C virus (HCV) exhibits genotype-specific variations in geographical
      distribution as a consequence of drug and immune induced evolution. Present study
      was aimed at discerning the distribution and prevalence of the various genotypes
      and subtypes of HCV in southern India. The HCV positive patient's serum was
      collected from different hospitals and blood banks from the states of Kerala,
      Tamil Nadu, Andhra Pradesh and Karnataka. Among 114 HCV positive samples, we
      could find only 44 isolates that are found both positive in ELISA and RT-PCR.
      From these samples 5' untranslated region (5'UTR) were amplified, sequenced and
      sub typed. Analysis of 5'UTR region of the 44 isolates shows that, genotypes 1,
      3, 4 and 6 are present with genotype 3 being the most frequent. The present study
      shows that HCV genotype 3 subtype B was the most prevalent, forming 47.7 % among
      the population in southern India. The present study urges for discovering novel
      therapeutic agents that should be specific to genotype 3 subtype B, for the
      management of HCV in southern India. 

PMID- 24293824
TI  - Occurrence and Partial Characterization of Lettuce big vein associated virus and
      Mirafiori lettuce big vein virus in Lettuce in Iran.
AB  - Mirafiori lettuce big vein virus (MiLBVV) and lettuce big vein associated virus
      (LBVaV) were found in association with big vein disease of lettuce in Iran.
      Analysis of part of the coat protein (CP) gene of Iranian isolates of LBVaV
      showed 97.1-100 % nucleotide sequence identity with other LBVaV isolates. Iranian
      isolates of MiLBVV belonged to subgroup A and showed 88.6-98.8 % nucleotide
      sequence identity with other isolates of this virus when amplified by PCR primer
      pair MiLV VP. The occurrence of both viruses in lettuce crop was associated with
      the presence of resting spores and zoosporangia of the fungus Olpidium brassicae
      in lettuce roots under field and greenhouse conditions. Two months after sowing
      lettuce seed in soil collected from a lettuce field with big vein affected
      plants, all seedlings were positive for LBVaV and MiLBVV, indicating soil
      transmission of both viruses. 

PMID- 24293825
TI  - Molecular Detection of Latent Apple chlorotic leaf spot virus in Elite Mother
      Plants of Apple.
AB  - Apple chlorotic leaf spot virus (ACLSV; family Betaflexiviridae genus
      Trichovirus) is one of the economically important latent virus infecting apple
      (Malus * domestica Borkh.). Reverse transcriptase polymerase chain reaction (RT
      PCR) procedures were used to amplify coat protein gene of ACLSV. Among 5 primer
      sets used, two primer sets (1F1R and 1F2R) amplified fragments of expected size
      (432 bp). Products visible on agarose gel were produced using templates extracted
      from apple leaves. The results were further validated by sequencing fragment of
      432 bp which was amplified from leaf of apple by using primer set 1F 1R.
      Comparisons with published sequences indicated that the isolate have very high 91
      % identity values to the corresponding region of ACLSV isolate from apple.
      Selected primer pair (1F1R) was further used for screening 42 elite mother plants
      collected from apple growing areas of Himachal Pradesh, India, where in 17 were
      found free from ACLSV. Use of NAD5 gene in mitochondrial mRNA of the apple as an
      internal control, reduced the risk of false negative results that may occur with
      routine RT-PCR assays. 

PMID- 24293826
TI  - Cloning and Sequence Analysis of N Gene of Transmissible Gastroenteritis Virus
      HYM-09 Isolated from Dog in China.
AB  - Transmissible gastroenteritis virus (TGEV) is the etiological agent of TGE, and
      dogs are potential carriers of TGEV. In this study, genomic RNA were extracted
      from TGEV designated HYM-09 isolated from dog naturally infected with TGEV. The
      nucleocapsid (N) gene of HYM-09 was amplified by RT-PCR and cloned into pMD18-T
      vector. The N gene cDNA was sequenced and encompassed an open reading frame of
      1,149 nucleotides, encoding a 382-amino acids protein. Sequence analyses of the N
      genes were performed, including homologous comparison, phylogenetic tree analysis
      and residue substitution analysis. The results showed that there existed some
      unique mutations in the HYM-09 isolate N gene, but HYM-09 N gene shared over 96 %
      homologous identities compared with 12 TGEV reference strains derived from other
      regions or countries respectively. The phylogenetic tree analysis revealed that
      the HYM-09 branched into the most strains group. This study shows that the
      nucleotide sequence analysis can form a base or further study on the mutation
      trend of non-porcine TGEV. 

PMID- 24293827
TI  - Newcastle disease virus in pakistan: genetic characterization and implication in
      molecular diagnosis.
AB  - Newcastle disease (ND) is a fatal and contagious disease that poses a constant
      threat to the poultry industry around the globe. Due to the complex clinico
      pathological picture and high genetic variability, the efficient diagnosis of NDV
      strains is a challenge. In an emerging wave of ND in the north of Pakistan,
      samples from six outbreaks in commercial poultry and two from healthy backyard
      poultry flocks were screened for NDV. A real-time PCR based on the fusion and
      polymerase genes of NDV detected all six isolates whereas a validated real-time
      PCR based on the matrix gene failed to detect any of these isolates, most likely
      due to substantial mismatches in the probe-binding site. All isolates have shown
      ICPI and MDT values similar to the velogenic form of NDV strains. The cleavage
      site in the F protein was found to be (112)RRQKR?F(117), typical of virulent NDV.
      Phylogenetic reconstruction, based on fusion and matrix genes, provided enough
      evidences to consider these isolates as a new subgenotype within genotype VII.
      This study raised concerns about the genetic variability of NDV circulating in
      Pakistan, and sensitivity of the assays for the detection of the NDV isolates in
      clinical samples. 

PMID- 24293828
TI  - Production and Application of Polyclonal Antibodies Against Recombinant Capsid
      Protein of Extra Small Virus of Macrobrachium rosenbergii.
AB  - Macrobrachium rosenbergii nodavirus along with a satellite virus, extra small
      virus (XSV) causes white tail disease (WTD) in the giant freshwater prawn M.
      rosenbergii. Infected M. rosenbergii postlarvae were collected from a hatchery in
      Kakinada, Andhra Pradesh. The gene coding the capsid protein of XSV was cloned in
      a bacterial expression vector pRSET A and the recombinant protein was expressed
      in Escherichia coli BL21(DE3)pLysS cells. The recombinant protein was purified by
      Nickel affinity chromatography. Polyclonal antibodies were produced in mice
      against the recombinant protein and the antibodies reacted specifically with the
      recombinant protein and XSV in WTD-infected tissues. This is the first report of
      detection of XSV using antibodies against recombinant capsid protein. 

PMID- 24293829
TI  - Molecular Characterization of a Nucleopolyhedrovirus Newly Isolated from Ophiusa
      disjungens in China.
AB  - Ophiusa disjungens nucleopolyhedrovirus (OpdiNPV) was newly found in Guangdong
      Province, China. Using BamHI, EcoRI, HindIII, PstI, XhoI, XbaI digestion, the
      size of the OpdiNPV genome was estimated to be 92,000 base pair. The pstI-G
      genomic fragment of OpdiNPV was cloned and sequenced. Searches of databases
      identified at least four open reading frames (ORFs) within this fragment. These
      ORFs encode odv-e66 (EU 623602), p87/vp80 (EU 732665), odv-ec43 (EU617337) and
      ac108 gene (EU 732666) respectively. The phylogenetic tree of NPVs based on the
      combined sequences of odv-ec43 and ac108 indicated that OpdiNPV was most closely
      related to Mamestra configurata NPV-A and Mamestra configurata NPV-B. The
      characterization of OpdiNPV in this paper would provide better understanding
      molecular properties of this virus and be helpful in the development of the newly
      isolated virus as a biopesticide or an engineered pesticide to control more
      species of insect pests. 

PMID- 24293830
TI  - Interaction of Paramecium caudatum and Picornaviruses.
AB  - In our paper we have researched the relationship between picornaviruses
      (poliovirus, foot-and-mouth disease virus and encephalomyocarditis virus) and
      Ciliata (Paramecium caudatum). We show that the number of Paramecium in medium
      sharply increased during coincubation with picornaviruses within 2-5 days. This
      cannot be explained only by the fact that viruses were nutrient source for
      Paramecium because in case of inactivated viruses the number of infusorians in
      medium increased a little. At the same time the titer of viruses harshly
      decreased whereas in the control group, which is free of Paramecium, the fall of
      titer was little. Picornaviruses were eliminated from medium if only living
      Parameciums were present in medium. After 7-9 days of coincubation only a few
      number of viruses were liberated from destroyed Parameciums. These results will
      be especially useful for management of reservoirs of picornaviruses in water and
      prevention of diseases. 

PMID- 24293831
TI  - Detection and molecular characterization of porcine picobirnavirus in feces of
      domestic pigs from kolkata, India.
AB  - Picobirnaviruses (PBVs) are small, non-enveloped, 35-41 nm virion with
      bisegmented double-stranded RNA genome. PBVs are widespread and were detected in
      feces of humans and a wide variety of animals. Domestic pig, one of the
      ubiquitous farm animal reported incessant association with a variety of viral
      zoonoses. The objective of our study is to find out the incidence of PBV
      infection in healthy domestic pigs. The study was conducted by collecting feces
      of healthy/asymptomatic pigs from a piggery located in an urban slum at Kolkata,
      India to detect PBV infections. All the 11 fecal samples were tested by
      polyacrylamide gel electrophoresis and reverse transcription-polymerase chain
      reaction assay. In this study, we report the first incidence of detection and
      molecular characterization of porcine PBV (BG-Por-2/2010 and BG-Por-7/2010) in
      feces of domestic pigs from India using the human PBV genogroup I specific primer
      pair: PicoB25(+) and PicoB43(-). Sequence comparison and phylogenetic analysis of
      partial RNA-dependent RNA polymerase gene of genome segment 2 revealed genetic
      relatedness to hitherto reported porcine, murine and human genogroup I PBVs from
      different geographical regions. This warrants a stringent global surveillance to
      study the potential zoonotic and emerging PBV infections. 

PMID- 24293832
TI  - Evaluation of rt-PCR assay for routine laboratory diagnosis of rabies in post
      mortem brain samples from different species of animals.
AB  - Rabies in domestic and wild animals continues to be a major public health threat
      in India. Rapid and accurate diagnosis of rabies in animals is therefore of
      utmost importance as the individuals who were in contact with the rabid animals
      are at a greater risk. A significant amount of diagnostic tissue samples
      submitted to our laboratory are often autolysed and the WHO recommended direct
      fluorescent antibody test (FAT) for rabies diagnosis cannot be used in such
      samples. In this pilot study we have evaluated three different diagnostic primer
      sets for rapid sensitive and specific detection of rabies genome from the brain
      samples of different species of animals. We have validated a sensitive RT-PCR
      assay using brain tissue samples from different species of animals such as cat,
      cattle, dog, mouse and human, for routine diagnosis of rabies. Our results show
      the potential of this assay as a confirmatory test when the FAT results are
      unreliable and also as an alternative diagnostic test in circumstances when the
      diagnostic samples are unsuitable for use in FAT. Furthermore the nucleotide
      sequence of nucleoprotein gene amplified using this assay can also be used for
      the molecular epidemiological study of the rabies viruses in India. 

PMID- 24293833
TI  - Prokaryotic expression and purification of highly soluble partial glycoprotein
      erns of Indian strain of classical Swine Fever virus.
AB  - Classical swine fever (CSF) or hog cholera, caused by a positive stranded RNA
      virus belonging to the genus Pestivirus of the Flaviviridae family, is highly
      contagious and fatal disease of pigs. We report the novel design of construct for
      production of highly soluble glycoprotein Erns fragment using prokaryotic
      expression system. A truncated fragment of the Erns gene (coding for aa 109-170)
      denoted as 'Erns-Ag' was subcloned and expressed as hexa-histidine tag fusion on
      both terminus of protein in Escherichia coli. The highly soluble recombinant Erns
      Ag protein with purity >95 % was purified by one step Ni-NTA affinity
      chromatography under native condition. Anti Erns-Ag polyclonal antibodies raised
      in guinea pig was found to react with CSFV antigen in infected MDCK cell line
      during immunoperoxidase test. The described methodology of producing a highly
      soluble recombinant protein with native conformation would likely to assist in
      development of differential diagnostic test as well as its application in raising
      hyperimmune sera for detection of CSFV antigen either in tissue materials or
      infected cell lines. 

PMID- 24293834
TI  - Glycoprotein C gene based molecular subtyping of a bovine herpesvirus -1 isolate
      from uttar pradesh, India.
AB  - Bovine herpesvirus -1 (BHV-1) is the etiological agent of many clinical syndromes
      in cattle which causes huge economic losses to the animal husbandry sector
      annually. Since the first report of its presence in India in 1976, the disease is
      considered to be endemic in the country. In the present study, a case of
      keratoconjunctivitis in a cow was investigated to find out the underlying cause
      of the condition. The clinical material (ocular swab) was tested by BHV-1
      glycoprotein D gene specific PCR using in house designed primers and found to be
      positive by the presence of a 212 bp DNA product in agarose gel electrophoresis.
      The virus was isolated in MDBK cell line in the third passage and the serum from
      the animal, was positive for antibodies against BHV-1 by ELISA. A 575 bp segment
      of the glycoprotein C gene of the isolate was amplified by PCR, cloned and
      sequenced. On phylogenetic analysis, it was seen that the sequence matched with
      published BHV-1.1 sequences from USA and Uruguay whereas it was divergent from
      Brazilian BHV-1.1 isolates. This study highlights the isolation, rapid and
      sensitive detection of BHV-1 virus from clinical cases and its subtyping by
      nucleotide sequencing and subsequent phylogenetic analysis which gives invaluable
      information about the molecular epidemiology of BHV-1 subtypes prevalent in the
      country. 

PMID- 24293835
TI  - Maternal nutritional deficiencies and interventions.

PMID- 24293836
TI  - Indian contribution to obstetrics and gynecology.

PMID- 24293837
TI  - Pearls and pitfalls of mesh surgery.
AB  - OBJECTIVES: This article attempts to offer balanced insight into the use of
      transvaginal mesh for pelvic organ prolapse especially in the light of the
      negative publicity in recent times. The role of transvaginal mesh has been in the
      limelight for a number of reasons and it is important to address this issue in an
      objective, fair, and balanced manner. The conventional approach to prolapse
      surgery has undergone a paradigm shift and the principles of mesh replacement
      surgery sharply contrast with many traditionally held beliefs. This has created a
      new set of challenges that has revealed a sharp division of opinion among
      specialists and sub-specialists alike. CONCLUSION: The article is an attempt to
      explain how mesh surgery can be safely and efficiently performed in carefully
      selected cases and is based on the combined wisdom of some of the leading
      surgeons in the sub-specialty today.

PMID- 24293838
TI  - Validation of Tamil Version of Cranley's 24-Item Maternal-Fetal Attachment Scale
      in Indian Pregnant Women.
AB  - BACKGROUND: Maternal-fetal attachment has not been formally studied among
      pregnant Indian women using Cranley's 24-item maternal-fetal attachment scale.
      OBJECTIVE: The purpose of this study was to validate the Cranley's 24-item
      maternal-fetal attachment scale (MFAS-24). METHODS: Consecutive pregnant Indian
      women of all trimesters were studied in Pondicherry, India. STATISTICAL ANALYSIS:
      The mean, standard deviation (SD), Cronbach's alpha, content validity index
      (CVI), correlation coefficient, and simple correlation analyses were calculated.
      RESULTS: 230 pregnant women of various sociodemographic, religious and
      educational background formed the sample. Mean age of sample was 23 (SD +/- 3)
      years, mean MFAS scores was 87.4 (SD +/- 10), mean GHQ scores was 14 (SD +/-
      1.2), and mean gestational age was 27.2 (SD +/- 7) weeks. Cronbach's reliability
      alpha of MFAS was high (0.71). There was no correlation between MFAS scores and
      gestational age or the pregnancy trimester. CVI of the scale, for the Tamil
      version was 0.72 and for the English version was 0.78. CONCLUSIONS: This study
      shows applicability of MFAS-24 in Indian settings also for measuring maternal
      fetal attachment.

PMID- 24293839
TI  - Partographic analysis of spontaneous labour at term in primigravida.
AB  - PURPOSE OF THE STUDY: To study the use of partogram in the analysis of
      spontaneous labour at term in primigravida with cephalic presentation.
      METHODOLOGY: Partographic analysis of labour was done in 200 primigravidae.
      Partographic variables are plotted, and the study population was divided into
      three groups. Group I: Cervix dilatation and descent curve falling to the left of
      alert line; Group II: Cervix dilatation and descent curve falling to the right of
      alert line; and Group III: Cervix dilatation and descent curve falling to the
      right of action line. Maternal and neonatal outcomes were studied in each of
      three groups. RESULTS: Amongst the 200 primigravid labours analysed, 133 (66.5 %)
      belonged to group I, 40 (20.0 %) belonged to group II and 27 (13.5 %) belonged to
      group III. Mean durations of active phases of labour were 4.1 h, 6.9 h and 9.6 h,
      in groups I, II and III, respectively. In group I, 130 women (97.7 %) delivered
      vaginally, 3 (2.3 %) underwent LSCS. In group II, 29 (72.5 %) delivered
      vaginally, 4 (10 %) delivered instrumentally and 7 (17.5 %) underwent LSCS, and
      in group III, 5 (18.5 %) delivered vaginally, 7 (25.9 %) delivered instrumentally
      and 15 (55.5 %) delivered by LSCS. CONCLUSION: Mean duration of active phase of
      labour increased as the partographic curve fell to the right of alert and action
      line. Increased rates of instrumental deliveries, LSCS, babies with lower APGAR
      score at 5 min, and NICU admissions were observed in group III compared with
      groups I and II.

PMID- 24293840
TI  - Episiotomies During Deliveries of Singletons in Cephalic Presentation: The
      Incidence can be Reduced.
AB  - OBJECTIVES: To verify if episiotomy rate could be reduced without compromising
      materno-fetal well-being. MATERIAL AND METHODS: This retrospective study was
      conducted between January 1 and December 31, 2010 in the maternity unit of the
      University Teaching Hospital Yaounde (Cameroon). All cases of singletons in
      cephalic presentation with episiotomies done or not done during deliveries were
      recruited. Data were analyzed by means of SPSS 12.0. The Fisher's exact test was
      used for comparison. The level of significance was 0.05. RESULTS: We performed
      163 episiotomies (9.6 %). Main indications were rigid perineum, fetal weight
      >=3,500 g, prolonged second stage of labor, and instrumental deliveries; 82.2 %
      of patients were nullipara. Mean 5th minute Apgar score was 9.2. Short term
      maternal complications were mainly perineal pain. Among fetuses delivered with or
      without episiotomy, no case of early neonatal death was recorded. CONCLUSIONS:
      The use of episiotomy can be reduced without increasing maternal and fetal
      morbidities.

PMID- 24293841
TI  - Outcome of gestational diabetes mellitus from a tertiary referral center in South
      India: a case-control study.
AB  - BACKGROUND: Carbohydrate intolerance is the most common metabolic complication of
      pregnancy. Gestational diabetes mellitus (GDM) poses numerous problems for both
      mother and fetus. The objective of this study was to compare the maternal and
      perinatal outcome between women with gestational diabetes mellitus and non
      diabetic women. STUDY DESIGN: A case-control study with 286 cases and 292 age
      matched controls was conducted for a period of 11 months (August 2007-June 2008)
      in Sree Avittom Thirunal Hospital, Thiruvananthapuram, India. MATERIALS AND
      METHODS: Universal screening was applied by means of glucose challenge test (GCT)
      using 50 g of glucose. If GCT >130 mg%, the patients were subjected to oral
      glucose tolerance test with 100 g of glucose. National Diabetes Data Group
      criteria was taken to assign patients to study group. These women were further
      followed up and the maternal and perinatal outcomes were assessed. STATISTICAL
      ANALYSIS: Univariate analysis was done by means of t test, Odd's ratio, Chi
      square test, and Fisher Exact test. P < 0.05 was taken as significant. RESULTS:
      The frequency of induction of labor was significantly higher than spontaneous
      labor (OR = 1.84, P = 0.001). 40.1 % GDM mothers and 35.8 % of non-diabetic
      mothers were delivered by Cesarean section. Premature rupture of membranes (PROM)
      was the most common complication of labor (OR = 1.66, P = 0.04). Babies of
      diabetic mothers had a positive trend toward prematurity (OR = 2.3, P = 0.007).
      Hypoglycemia was the most common neonatal complication (OR = 11.97, P < 0.001)
      and nine babies of diabetic mothers were macrosomic (OR = 5.2, P = 0.02).
      CONCLUSIONS: Maternal morbidities and neonatal complications such as neonatal
      hypoglycemia, macrosomia, and prematurity were significantly higher in GDM.

PMID- 24293842
TI  - Association of umbilical coiling index by colour Doppler ultrasonography at 18-22
      weeks of gestation and perinatal outcome.
AB  - OBJECTIVE: To study the association between antenatal umbilical coiling index
      (aUCI) and perinatal outcome. METHODS: 600 primigravidas with uncomplicated
      singleton pregnancies had an ultrasonography between 18 and 22 weeks of gestation
      for aUCI by colour Doppler. The aUCI was calculated as the reciprocal of the
      distance between a pair of coils. It was then correlated with the following
      pregnancy outcomes: birth weight, mode of delivery, meconium staining of liquor,
      Apgar scores and gestational age. The results were statistically analysed by
      chi(2)-test. RESULTS: The mean aUCI was 0.41. Undercoiling was associated with
      spontaneous preterm delivery (47.87 %), low Apgar score (52.13 %), LBW (52.59 %),
      FGR (21.28 %) and NICU admission (76.34 %). Overcoiling was associated with
      preterm deliveries (65.38 %), increased caesarean sections (61.54 %), meconium
      staining of liquor (67.31 %), low Apgar score (63.46 %) and NICU admission (72.55
      %). There was a positive strong correlation between aUCI and birth weight (r =
      +0.426). CONCLUSIONS: Abnormal coiling is strongly correlated with low birth
      weight.

PMID- 24293843
TI  - The art of fetoscopy: a step toward minimally invasive fetal therapy.
AB  - PURPOSE: To study the feasibility, learning curve, and safety of fetoscopy, so
      that fetal surgery can be confidently performed in ongoing pregnancies. METHODS:
      Fetoscopy was performed at 12-20 weeks of gestation, in 12 women with fetal
      congenital malformations and/or for termination of pregnancy, under local
      anesthesia using fine fetoscopes ranging from 1 to 2-mm diameter. The fetal parts
      and placenta were examined for clarity of vision, identification, and anomalies.
      RESULTS: Fetoscopy required great skill, patience, and extensive use of
      ultrasound for correct orientation. Visualization was better with endoscope of 2
      mm diameter. Laser coagulation of placental vessels using diode laser system was
      possible in the last two cases. There were no major complications. CONCLUSIONS:
      Fetal endoscopy is a feasible procedure, safe in experienced hands but has an
      appreciable learning curve.

PMID- 24293844
TI  - Evaluation of outcomes associated with placement of elective, urgent, and
      emergency cerclage.
AB  - OBJECTIVES: The aim of this study was to assess pregnancy outcomes after cervical
      cerclage. METHODS: A retrospective analysis of all cervical cerclages placed at
      Al Qassimi Hospital from 2004 to 2008 was performed. The primary outcome of
      interest was prolongation of pregnancy beyond 36 wks. Secondary outcomes were
      premature rupture of membranes, birth weight <1,500 g, and neonatal death.
      RESULTS: Cerclage was placed in 145 women: 112 elective, 16 urgent, and 17
      emergency groups. Delivery beyond 36 weeks occurred in 79.4, 73.3, and 47.1 % in
      the elective, urgent, and emergency groups, respectively, p = 0.011. When
      comparing between elective, urgent, and emergency groups, incidences of low birth
      weight were 9.8, 13.3, and 33.3 %, respectively, p = 0.06, and premature ruptures
      of membranes occurred in 7.2, 6.3, and 17.7 %, respectively, p = 0.16. There were
      five neonatal deaths. CONCLUSION: Therefore, although cerclage gives best results
      when it is performed as an elective procedure, emergency cerclage still confers
      some benefits.

PMID- 24293845
TI  - A Case Series of Uterine Rupture: Lessons to be Learned for Future Clinical
      Practice.
AB  - OBJECTIVE: In this article, we try to discuss risk factors and diagnostic
      difficulties for uterine rupture. METHODS: Case series of 12 cases of uterine
      rupture observed in the Norfolk and Norwich University Hospital in the UK, with
      an average yearly birth rate of 6,000 deliveries, over a 6-year period. RESULTS:
      In the present case series, there was no maternal mortality, and uterine rupture
      was a rare occurrence (12 in 36,000 births). Uterine rupture is associated with
      clinically significant uterine bleeding, fetal distress, expulsion or protrusion
      of the fetus, placenta or both into the abdominal cavity, and the need for prompt
      cesarean delivery and uterine repair or hysterectomy. The risk factors for
      rupture include previous cesarean sections, multiparity, malpresentation and
      obstructed labor, uterine anomalies, and use of prostaglandins for induction of
      labor. Previous cesarean section is, however, the most commonly associated risk
      factor. The most consistent early indicator of uterine rupture is the onset of a
      prolonged, persistent, and profound fetal bradycardia. CONCLUSION: In this case
      series, we suggest that the signs and symptoms of uterine rupture are typically
      nonspecific, which makes diagnosis difficult. Delay in definitive therapy causes
      significant fetal morbidity. The inconsistent signs and the short time in
      prompting definitive treatment of uterine rupture make it a challenging event.
      For the best outcome, vaginal birth after previous cesarean section needs to be
      looked after in an appropriately staffed and equipped unit for an immediate
      cesarean delivery and advanced neonatal support.

PMID- 24293846
TI  - Risk factors and clinical aspects of recurrent invasive cervical carcinoma.
AB  - OBJECTIVES: Recurrence of cervical cancer is one of the important and plausible
      discussions in oncology especially in patients with advanced stages. The purpose
      of this study was to introduce probability invasive cervical carcinoma recurrence
      as well as determining characteristics and the prognostic factors of this entity.
      METHODS: A retrospective study was designed to identify risk factors and pattern
      of uterine cervical carcinoma recurrence evaluating the outcome of 36 registered
      patients. Recurrence was defined based on clinical or para-clinical documentation
      over at least 6 months after complete remission following surgery or
      radiotherapy. Treatment consisted of a radiosurgical combination and exclusive
      radiotherapy. RESULTS: Mean age in selected patients is 54.8 +/- 12.0 years. The
      pathological reports of primary diagnosis are squamous cell carcinoma in 94.44 %
      and adenocarcinoma in remaining patients. Mean duration of recurrence among
      patients is 2.75 +/- 1.5 years after the initial treatment. Metrorrhagia is
      mostly revealing symptom which patients present in recurrent episode. Usually,
      the recurrence of cervical cancer is presented in pelvic cavity locally. Marginal
      involvement is documented in 50 % of cases and lymph node in 33.3 % of patients
      with recurrent episode being involved. Most important prognostic factors are
      improper treatment (16.66 % of cases) after initial diagnosis. CONCLUSIONS:
      Prognostic factors such as selection of appropriate method for treatment are an
      important point for reducing the rate of recurrence. Moreover, warning patients
      about symptoms and frequent episodes of follow up is necessary for early
      diagnosis of recurrence.

PMID- 24293848
TI  - Vesical calculus: an uncommon cause of obstructed labor.

PMID- 24293847
TI  - Pure accelerated radiation versus concomitant chemoradiation in selected cases of
      locally advanced carcinoma cervix: a prospective study.
AB  - OBJECTIVE: This non-randomized study was conducted to assess and compare the
      response and safety of true accelerated radiation alone to concomitant
      chemoradiation in locally advanced squamous cell carcinoma of the uterine cervix.
      METHODS: Sixty patients with locally advanced squamous cell carcinoma of the
      uterine cervix, FIGO Stages (2009) IB2-IIIB were non-randomized to receive six
      fractions per week of external beam radiation (EBRT) (will be henceforth referred
      to as Arm A or Study arm or pure accelerated radiation arm) and five fractions
      per week of EBRT and chemotherapy with inj cisplatin 40 mg/m(2) i.v. every Monday
      during the course of EBRT (will be henceforth referred to as Arm B or Control arm
      or chemoradiation arm). RESULTS: The median follow-up was 15 months in both the
      arms. The overall treatment time was 56.54 days for Arm A and 62.59 days for
      patients in Arm B (P value < 0.000**). The median EBRT time was 32.25 days in Arm
      A and 38.85 days in Arm B, a statistically significant delay for patients of
      chemoradiation Arm B (P value < 0.000**). The response assessment at the end of
      the study was not statistically different among the patients in both the
      treatment arms (P value 0.631). CONCLUSION: The early responses to treatment with
      pure accelerated EBRT are non-inferior to concomitant chemoradiation and the
      acute toxicities are lesser.

PMID- 24293849
TI  - Pregnancy after unilateral salpingo oophorectomy and contralateral cystectomy.

PMID- 24293850
TI  - Spontaneous rupture of spleen during pregnancy.

PMID- 24293851
TI  - An unusual case of rupture of right horn of bicornuate uterus at eighteen weeks
      of gestation.

PMID- 24293854
TI  - A case of cervical ectopic pregnancy: successful therapy with methotrexate.

PMID- 24293855
TI  - Successful outcome of a rare case of ruptured sinus of valsalva aneurysm in
      pregnancy.

PMID- 24293856
TI  - Strangulating ileocolic intussusception in pregnancy.

PMID- 24293857
TI  - Transient osteoporosis of hip and lumbar spine in pregnancy.

PMID- 24293858
TI  - Ovarian pregnancy: report of two cases.

PMID- 24293859
TI  - A successful pregnancy outcome after antenatal surgical decompression of Arnold
      Chiari malformation.

PMID- 24293860
TI  - Acardius acephalus: "headless-heartless nine-month life".

PMID- 24293861
TI  - Triplets with Two IUFD with IUGR of Live Fetus with DIC in a Patient with BOH and
      Septate Uterus.

PMID- 24293862
TI  - Successful pregnancy outcome in a case of protein s deficiency.

PMID- 24293863
TI  - Full-term viable broad ligament pregnancy surgically managed with favorable feto
      maternal outcome.

PMID- 24293864
TI  - Successful pregnancy outcome following conservative management of morbidly
      adherent placenta.

PMID- 24293865
TI  - Antepartum eclampsia with posterior reversible encephalopathy syndrome.

PMID- 24293866
TI  - Pregnancy in survivor of acute lymphoblastic leukemia with thalassemia trait.

PMID- 24293867
TI  - Pregnancy in Non-communicating Half of Septate Uterus.

PMID- 24293868
TI  - A case of folic Acid allergy in pregnancy.

PMID- 24293869
TI  - Successful outcome of eisenmenger with term pregnancy.

PMID- 24293870
TI  - Pregnancy with carcinoma cervix.

PMID- 24293871
TI  - Pre-natal Ultrasonographic Diagnosis of Cystic Meconium Peritonitis with
      Intestinal Atresia and Its Post-natal Management.

PMID- 24293872
TI  - Intrafetal laser ablation of umbilical vessels in acardiac twin with successful
      outcome.

PMID- 24293873
TI  - PMD Initially Diagnosed as Partial Mole.

PMID- 24293874
TI  - Complete Cervical Stenosis Following Cesarean Section & VVF Repair.

PMID- 24293875
TI  - Bilateral huge adenocarcinoma of the ovary.

PMID- 24293876
TI  - Benign cytic teratoma of ovary perforating into the urinary bladder: a rare case.

PMID- 24293877
TI  - Inadvertent intraarterial injection leading to gangrene: a rare but devastating
      postoperative complication.

PMID- 24293878
TI  - Metastatic clear cell carcinoma of cervix.

PMID- 24293879
TI  - Fallopian tube carcinoma.

PMID- 24293880
TI  - Squamous cell carcinoma developing in mature cystic teratoma of the ovary: a rare
      case.

PMID- 24293881
TI  - XY Female with Complete Androgen Insensitivity Syndrome with Bilateral Inguinal
      Hernia.

PMID- 24293882
TI  - Malignant mixed mullerian tumor of endometrium coexisting with bilateral
      papillary serous adenocarcinoma of fallopian tube: a rare case report.

PMID- 24293883
TI  - Heterogenous presentation of chorioadenoma destruens.

PMID- 24293884
TI  - Complete androgen insensitivity syndrome.

PMID- 24293885
TI  - A success story in congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      characterized by enzyme defects in adrenal steroidogenic pathways. CAH due to 21
      hydroxylase deficiency accounts for 95 % of cases. This case was diagnosed to
      have simple virilizing type of CAH and started on dexamethasone, and underwent
      genitoplasty and clitoroplasty at 25 years of age, then was married 3 years after
      surgery and conceived spontaneously 2 years after marriage, to deliver a healthy
      male baby. Thus, proper diagnosis and treatment with steroids and genitoplasty
      can give females with CAH a normal sexual, normal menstrual, and reproductive
      function. 

PMID- 24293886
TI  - Endodermal sinus tumor of the vagina in a child.

PMID- 24293887
TI  - Mayer-Rokitansky-Kuster-Hauser Type-B Anomaly with MURCS Association and Gonadal
      Dysgenesis.

PMID- 24293888
TI  - Benign fibrous histiocytoma of vulva: rare case.

PMID- 24293889
TI  - Nodular vulvar melanoma: a rare tumor with worse prognosis.

PMID- 24293890
TI  - Abdominal Incision Metastasis from Carcinoma Cervix After Wertheim's
      Hysterectomy.

PMID- 24293891
TI  - Primary granulocytic sarcoma of ovary.

PMID- 24293892
TI  - A rare presentation of endometriosis.

PMID- 24293893
TI  - Atypical case of choriocarcinoma with breast metastasis.

PMID- 24293894
TI  - Cervical priming and scar rupture.

PMID- 24293895
TI  - Oral cancer-curse, cure and challenge.

PMID- 24293896
TI  - Analysis of Trauma Outcome Using the TRISS Method at a Tertiary Care Centre in
      Pune.
AB  - Out of the various systems used to assess the outcome of polytrauma patients,
      trauma and injury severity score (TRISS) is considered as the standard tool for
      evaluating the performance of trauma centres. The present study was carried out
      to evaluate the outcome of severely injured patients using the TRISS method in a
      developing country like India and to compare it with the major trauma outcome
      study (MTOS). A prospective study of 300 patients of trauma was done. Outcome
      assessment was done for the severely injured patients using the TRISS method.
      Road traffic accidents (213 cases) were the most common cause of injury. Fifty
      seven (19%) cases were severely injured defined as having an injury severity
      score >=16. Outcome assessment was done for these patients using the TRISS
      method. The predicted mortality was 15.7%, while the observed mortality was
      33.3%. The mean revised trauma score was 6.63 +/- 1.79 and the mean injury
      severity score (ISS) was 23.7 +/- 8.17. Compared to the MTOS, the patients in the
      present study had more severe injuries with higher mortality. The present method
      of comparison of trauma care, i.e. TRISS which uses the MTOS coefficients, does
      not accurately predict survival of trauma patients in the developing countries as
      indicated by the present and other studies. There is a need for developing a
      national trauma registry to derive new coefficients for trauma scoring for the
      Indian subcontinent so that the quality of trauma care can be compared with that
      in the developed countries. 

PMID- 24293897
TI  - Multi detector computed tomography in the diagnosis of bowel injury.
AB  - Bowel Injuries are uncommonly associated with traumatic abdominal injuries.
      However, they are associated with significant morbidity and mortality and require
      operative intervention unlike solid organ injuries. Hence, early diagnosis is of
      paramount importance. Computed tomographic (CT) scan is a well-established and
      highly accurate imaging modality for the detection of solid organ injury after
      blunt abdominal trauma. However, its role in diagnosing hollow viscus injury
      remains controversial. The aim of our study was to analyze the accuracy of
      multidetector CT (MDCT) in the diagnosis of bowel injury. Imaging features of
      surgically proven cases of bowel injury were identified over 8-year period (i.e.,
      from January 2003 to December 2010) and were retrospectively analyzed. There were
      32 patients with age range of 3-90 years. There was only one female. Sensitivity
      of various CT signs specific to bowel injury (i.e., extravasation of contrast and
      discontinuity of bowel wall) was 15.62, and 28.12%, respectively. While that of
      signs suggestive of bowel injury were pneumoperitoneum, 62.5%; gas in the
      vicinity, 40.62%; bowel wall hematoma, 21.87%; bowel wall thickening, 75%;
      ascites, 78.12%; mesenteric hematoma, 46.87%; and mesenteric stranding, 40.62%.
      Based on the major and minor signs, a diagnosis of bowel injury could be made in
      all patients except one. The minor signs showed a higher sensitivity than the
      major signs. Hence, we recommend that multidetector CT should be used as the
      modality of choice in case of patients with suspected bowel injury. We also
      suggest that the minor signs should be given as much importance as the major
      signs. 

PMID- 24293898
TI  - Role of epidermal growth factor in healing of diabetic foot ulcers.
AB  - Diabetes mellitus may lead to amputation in 3 % of population. Risk for
      amputation is 15 folds in diabetics compared with nondiabetics. The aim of the
      study is to compare the outcome of dressing a diabetic foot ulcer with epidermal
      growth factor with that of conventional dressing with normal saline. The patients
      with diabetic foot were divided into study and control groups of 20 each. In the
      study group, epidermal growth factor (EGF) gel was used as dressing; in control
      group, dressing was done with normal saline. Treatment was given for 8 weeks or
      until ulcer healed, whichever occurred first. Evaluation of healing response was
      recorded on 1, 3, 5, and 8 weeks. After the first week of dressing 90 % of the
      study group and 30 % of the control group patients showed decrease in wound
      soakage, size, and increase in proliferation of healthy granulation tissue. After
      the eighth week of dressing in the study group, 80 % of the patients showed
      complete response to EGF application. Whereas in control group only 35 % of the
      patients showed complete response. Duration of hospital stay in the study group
      was lower as compared with the control group. EGF dressing causes early healing
      up to first 5 weeks as compared with conventional dressing. The results in
      healing were not significantly different in two study groups after 8-week
      duration. Hospital stay was lower in the study group as compared with the control
      group. 

PMID- 24293899
TI  - Impact of trauma system preparedness on the outcomes of severe injuries among
      child populations.
AB  - Severe child trauma poses a heavy burden upon the public's health and the
      nations' economies, in terms of mortality, morbidity, and disability. The burden
      varies by the maturity level of the adopted trauma system. This work aimed to
      identify the impact of trauma system maturity on the outcomes of care of severely
      injured children. Discharge data for the hospitalized trauma children in Florida
      (mature trauma system) and Indiana (immature trauma system) were retrospectively
      analyzed. All severely injured children, 1-15 years of age with an injury
      severity score >=25 during 1999-2000 were included. Assessment involved the
      differences in specified treatment procedures, survival rates, hospital length of
      stay, and the need for post-hospital institutional care. Analysis revealed that
      Indiana children significantly stay longer in hospital, and that no differences
      in the rates of patient mortality, discharge-home, and selected procedures were
      found. Trauma system maturity impacts the volume and complexity of interventions,
      as well as the mortality, morbidity, and disability associated with severe
      children and adolescent trauma. The cost of such burden could be directed to
      improving the quality of the state's injury management services. 

PMID- 24293900
TI  - Comparative Study between Staplers and Conventional(Hand-Sewn) Anastomosis in
      Gastrointestinal Surgery.
AB  - Conventional (hand-sewn) technique of intestinal anastomosis has been in vogue
      for decades. Staplers which were developed to simplify surgery began to have
      significant impact. To compare staplers versus conventional anastomosis with
      respect to certain intra operative and post operative parameters. Prospective
      study from November 2008 to October 2010 in Hyderabad at OSMANIA, GANDHI, MNJ
      CANCER hospitals. 120 patients were divided into three groups of 40 each,
      depending on the surgery like posterior gastrojejunostomy, distal gastrectomy and
      reconstruction (Billroth II) and colorectal anastomosis. Of these 40 patients, 20
      were in hand-sewn group and the other 20 in stapler group. Unpaired 't' test was
      used to find 'p' value . 'p' value less than 0.05 was considered statistically
      significant. Total operating time was shortened in stapler group. No significant
      difference was found in terms of restoration of intestinal function, post
      operative hospital stay, post-operative complications like anastomotic leak.
      Staplers can expedite surgery. They have better access to difficult-to-reach
      areas. Thus staplers can be beneficial though one should not forget the art of
      conventional suturing. 

PMID- 24293901
TI  - Primary cutaneous zygomycosis in India.
AB  - Cutaneous zygomycosis remains underdiagnosed despite being frequently
      encountered. Delay in the diagnosis contributes to delay in treatment, and a
      resultant high morbidity and mortality. A retrospective analysis of the reported
      cases of cutaneous zygomycosis from India was made using various search engines
      and cross-referencing from available manuscripts. A total of 42 publications from
      India on the topic were identified, since the first reported case of primary
      cutaneous zygomycosis by Veliath et al. (1976). There are 130 described cases of
      cutaneous zygomycosis with an overall mortality of 35 %. The commonest zygomycete
      identified was Apophysomyces elegans, and the commonest predisposing factor was
      breach of the skin. Surprisingly, diabetes was reported only in 36 cases (27.69
      %). It is important to be aware of this unusual but fatal infection in order to
      manage it properly and have a good outcome. 

PMID- 24293902
TI  - Cecal volvulus.
AB  - A twisted loop of the bowel and its mesentery on a fixed point is known as
      volvulus and it may arise more frequently in the sigmoid colon and cecum. Cecal
      volvulus as an uncommon cause of acute intestinal obstruction is axial twist of
      the cecum, ascending colon and terminal ileum around their mesenteric pedicles.
      Although there are many different etiologic and predisposing factors for cecal
      volvulus, exact etiology is most likely multifactorial in presence of mobile
      cecum. Its clinical presentation is highly variable, ranging from intermittent
      episodes of abdominal pain to abdominal catastrophe depending on pattern,
      severity and duration of cecal volvulus causing intestinal obstruction. Due to
      its rarity and nonspecific presentation, preoperative diagnosis is rarely
      achieved in most cases. Abdominal radiographs as an initial diagnostic test are
      usually abnormal and can detect cecal volvulus in half of cases. Nowadays,
      computerized tomography is used for more accurate diagnosis and differentiation
      from other acute emergent conditions. Resection with right hemicolectomy and
      primary ileocolic anastomosis has been recommended for surgical treatment of
      cecal volvulus. 

PMID- 24293903
TI  - Actinomycetoma-the welsh regimen in a rural Indian scenario.
AB  - We describe a case of Actinomycetoma foot which presented to us after 3yrs of
      onset of symptoms.We have attempted a chemotherapeutic treatment regime and are
      reporting the healing changes that have taken place radiologically and
      macroscopically. A review of literature has been done of various treatment
      regimens used for Actinomycetoma foot and used and their practical applications
      in rural hospital. 

PMID- 24293904
TI  - Percutaneous cyanoacrylate glue embolization for peripheral pseudoaneurysms: an
      alternative treatment.
AB  - Post-traumatic pseudoaneurysms are rare in the peripheral arteries and usually
      occur as a late sequel of trauma. Surgery has traditionally been considered as
      the gold standard of therapy for traumatic peripheral pseudoaneurysms. We report
      2 cases of post traumatic pseudoaneurysms successfully treated by percutaneous
      cyanoacrylate glue (N-Butyl 2 cyanoacrylate) embolization. This method offers
      complete exclusion of the pseudoaneurysm, at the same time avoiding the morbidity
      of open surgery. 

PMID- 24293905
TI  - Scarless cholecystectomy: laparoscopic cholecystectomy with abdominoplasty.
AB  - Three patients presented to our hospital with abdominal wall laxity and
      symptomatic cholelithiasis. All of them wanted to undergo a cosmetic procedure
      (abdominoplasty) to reduce the abdominal wall laxity. They were also diagnosed to
      have cholelithiasis and had intermittent episodes of pain in the right upper
      quadrant of the abdomen. The ports for laparoscopic cholecystectomy were made in
      such a way that all the ports sites were removed in the skin flap that was
      excised during abdominoplasty, and there was no scar in the upper abdomen. The
      procedure was completed without leaving any telltale signs of laparoscopic
      cholecystectomy, and this led to a better cosmetic result from the patients'
      point of view. 

PMID- 24293906
TI  - Is this phantom pain?
AB  - Right upper quadrant abdominal pain may be due to many causes, and at times may
      give rise to diagnostic dilemma. We present here a young lady with biliary type
      of pain who was eventually found to have gall bladder agenesis with aerobilia, in
      the absence of prior biliary intervention. 

PMID- 24293907
TI  - Venous aneurysm complicating dialytic arteriovenous fistula.
AB  - A case of venous aneurysm complicating arteriovenous fistula created for chronic
      haemodialysis is presented. The patient underwent successful ligation and
      excision of the fistula and creation of a fistula on the opposite limb. 

PMID- 24293908
TI  - Evaluation of effect and comparision of superoxidised solution (oxum) v/s
      povidone iodine (betadine): points to ponder.

PMID- 24293909
TI  - Learning from mistakes: femoral vein cannulation-need for basic clinical
      guidelines.

PMID- 24293910
TI  - Surgical management of resistant priapism.
AB  - We report a 31 year old patient, presented with painful erection since 48 hours.
      There was no known predisposing factor on history and examination. Surgery for
      priapism is rarely indicated nowadays but conservative management failed to
      achieve detumescence in our case. So Winter's shunt surgery was done which failed
      then a formal shunt was created between corpora cavernosa and spongiosum which
      also failed to achieve detumescence. After 4 days - a formal left side cavernosa
      saphenous shunt procedure was done and detumescence achieved within 24 hrs
      .Follow up showed good results. 

PMID- 24293911
TI  - Gastric gangrene "an iatrogenic misadventure".
AB  - In gastrointestinal system gangrene commonly involves intestines. Involvement of
      stomach is a rare finding. Herein we describe a case of gastric gangrene
      secondary to herniation of stomach through an iatrogenic defect. Gangrene of the
      stomach is a rare and a catastrophic occurrence as stomach is a highly
      vascularised organ. Gastric gangrene could be secondary to atherosclerosis,
      arterial embolism, iatrogenic gelfoam embolism, venous thrombosis, gastric
      volvulus, bulimia nervosa, endoscopic haemostatic injections, diaphragmatic
      hernia and infectious gastritis. Most reported cases have occurred due to gastric
      volvulus (Amin El-Gohary and Etiaby, Paedr Surg Intl 9:486-488, 1994; Al-Salem,
      Pediatr Radiol 30(12):842-5, 2000). Few cases have been reported as complicated
      hernias either a Bochdalek hernia (Ghanem, Chankun, Brooks, BJS V74(9):779, 2005)
      or as peristomal hernias which initially lead to gastric outlet obstruction
      (Ellingson, Maki, Kozarek, Patterson, J Clin Gastroenterol 17(4):314-6, 1993). 

PMID- 24293912
TI  - Asymptomatic infantile cystic nephroma: a diagnostic dilemma.
AB  - Cystic nephroma, also called multilocular cystic nephroma, is a relatively rare,
      nongenetic, benign, unilateral, renal multicystic lesion. The non-specific
      clinical findings and the poor contribution of imaging examinations make the
      preoperative diagnostic dilemma from other cystic renal neoplasia; thus
      nephrectomy seems to be the most preferable treatment. We report a case of cystic
      nephroma in 11 months old male child presented with asymptomatic lump in abdomen.
      After a series of examinations including abdominal ultrasound, intravenous
      pylography and computed tomography, he underwent radical nephrectomy and
      diagnosis is confirmed on histopathology. 

PMID- 24293913
TI  - Giant malignant cystic pheochromocytoma: a case report.
AB  - Cystic malignant pheochromocytomas are uncommon. Differing from solid
      pheochromocytomas, which produce catecholamines and present adrenergic syndrome,
      cystic pheochromocytomas, may not produce these. Preoperative diagnosis may be
      difficult. Ct scan is useful for preoperative management. In this report, we
      describe a case of a giant malignant cystic pheochromocytoma in a young woman (17
      years old) which presented as giant abdominal mass. The malignancy was confirmed
      by the presence of liver metastasis. Two years after curative resection, the
      patient is in good health with no recurrence. 

PMID- 24293914
TI  - Phlegmonous appendicitis and mobile cecum syndrome simulating ileal duplication
      cyst in a 9 year old girl.
AB  - Mobile cecum syndrome is a rare entity that produces recurrent lower abdominal
      pain mimicking appendicitis. Appendicitis developing in a mobile cecum at an
      abnormal location eludes the clinical diagnosis and confuses the clinicians
      unless a high index of suspicion is harbored. We present an unusual case of
      phlegmonous appendicitis in a mobile cecum masquerading as duplication cyst of
      ileum in a 9 years old girl. 

PMID- 24293915
TI  - Papillary carcinoma of the breast- case reports and review of literature
      regarding management guidelines.
AB  - Papillary carcinoma of the breast is a very rare entity accounting for approx 1 %
      of all breast carcinomas. The diagnosis is difficult due to different clinical
      and radiological features. Pathological diagnosis is conclusive. Being aware of
      the diagnostic difficulties and differences in management from the more commonly
      reported IDC, makes it easier to treat these patients. Because this is an
      uncommon disease, we report here 2 cases recently diagnosed and treated in our
      hospital. We have also reviewed the literature regarding the diagnosis, treatment
      and prognosis of these patients. 

PMID- 24293916
TI  - Hypersensitivity to titanium: a less explored area of research.
AB  - Titanium is considered as an excellent biocompatible metal and it is used in
      implant dentistry. Literature suggests that Ti can induce clinically relevant
      hypersensitivity and other immune dysfunctions in certain patients chronically
      exposed to this reactive metal. At the same time, no standard patch test for Ti
      has so far been developed, and positive reactions to Ti have therefore only
      rarely been demonstrated with skin testing. This article reports about the
      corrosion of dental implants, their significance when hypersensitivity is
      present, and the literature available till date regarding hypersensitivity of
      titanium. 

PMID- 24293917
TI  - A comparative study of mandibular incisor relation to the lingual frenum in
      natural dentition and in complete denture wearers.
AB  - The determination of the occlusal vertical dimension and proper positioning of
      the anterior teeth are major factors in making complete dentures which will give
      optimum service. In this study, efforts were made to evaluate the reliability of
      measurement of vertical distance between the anterosuperior most point on the
      lingual frenum and mesioincisal edges of mandibular central incisors in natural
      dentition among different age groups and in complete denture wearers. Three
      hundred dentulous subjects belonging to different age groups and hundred
      edentulous patients wearing complete dentures were selected. The dentulous group
      was divided into three groups, group I (20-40 years), group II (41-60 years),
      group III (61 years and above) and the edentulous subjects being group IV ( 40-60
      years). Mandibular irreversible hydrocolloid impression (Alginate) was made using
      modified stock tray. In edentulous subjects impression was made with denture in
      position. The vertical distance between anterosuperior most point on the lingual
      frenum and mesioincisal edges of mandibular central incisors was measured on the
      dentulous casts and casts of complete denture wearer using dental surveyor and
      the vernier calipers. The values were tabulated and statistically analysed. The
      mean vertical distance between anterosuperior most point on the lingual frenum
      and mesioincisal edges of mandibular central incisors among dentulous subjects
      was 12.3 mm and among complete denture wearers was found to be 13.2 mm. There was
      no significant variation in the mean vertical distance among dentulous subjects
      belonging to different age groups. At 5 % significance level, statistically there
      was a significant difference in the mean vertical distance between group I and
      group IV; group II and group IV. 

PMID- 24293918
TI  - A positional analyzer for measuring centric slide.
AB  - Centric relation (CR) has been considered mainly as a position posterior to
      habitual occlusion or maximum intercuspation (MI). Awareness of the tooth
      contacts relationship in centric relation position of the mandible and diagnosing
      the case from this position is essential to consistently select treatment plans
      that will allow to treat to or very near to centric relation occlusion. Centric
      slide and other occlusal relationships are conceived of as positions, which can
      be studied in three dimensions. Clinically, the difference between the two
      occlusal positions namely CR and MI (centric slide) can easily be determined, but
      for a more precise evaluation of its length and directions, an occlusal analysis
      on articulator mounted casts is necessary. Study was under taken on the mounted
      casts of ten subjects on a semi adjustable articulator to which a stylus and
      recording table was devised and attached for measurement of CR-MI slide in the
      three planes namely anterior-posterior, medio-lateral and superior-inferior. It
      was found that there was a displacement from CR to MI (centric slide) in all the
      three planes and numerically the mean slide was 0.688 +/- 0.623, 0.261 +/- 0.627
      and 0.127 +/- 0.541 mm in the antero-posterior, medio- lateral and superior
      inferior directions respectively. The stylus and table attachment may be an
      accurate indirect method to measure positional changes of the condyle in 3D. 

PMID- 24293919
TI  - An evaluation of shade differences between natural anterior teeth in different
      age groups and gender using commercially available shade guides.
AB  - Shade selection with the help of shade guides and color matching the restorations
      to the natural dentition continues to be one of the most perplexing and
      frustrating problems in fixed prosthodontics. The purpose of the study was to
      evaluate the shade differences of the natural anterior teeth in different age
      groups and gender, within the cross sectional Bangalore, Karnataka population,
      using commercially available shade guides. The shade of a cross section of the
      population comprising of 400 subjects of both the sexes (800 incisors; 400
      maxillary central incisors; 400 mandibular central incisors) visiting the
      outpatient Department of Government Dental College was selected randomly and
      evaluated visually by a single observer using three commonly used shade guides
      i.e. Vita Lumin, Chromascop and the Vita 3D Master. The incidence of the most
      common shades in the different age groups and gender using these shade guides was
      obtained and this data was subjected to the chi(2) test (p < 0.05-significant).
      The most common shade for the maxillary and mandibular incisors in the younger
      age group is A2/2R1.5/140 and A1/1M2/120 for the males and females using Vita
      Lumin, Vita 3D Master and Chromascop shade guides respectively. In the advanced
      age group the most common shade for the maxillary and mandibular incisors is
      A2/2R2.5/140 using the same order of shade guides. However the results showed no
      statistical significance in shade variation in males and females in different age
      groups using different shade guides. Although the incidence of males with darker
      teeth as compared to females was higher; the study showed no statistical
      significant correlation between shade differences in both the sexes. It is also
      observed that there is a significant darkening of teeth as the age advances. 

PMID- 24293920
TI  - Denture marking for forensic identification using memory card: an innovative
      technique.
AB  - Identification of individuals in crime or mass disaster is a daunting task for
      the forensic experts. The purpose of this study is to evaluate the feasibility of
      using a memory card for the forensic identification of dentures. The memory card
      was programmed with all the relevant information regarding the patient
      identification and the photograph of the patient. A recess was made in the
      maxillary denture's polished surface on the palatal aspect. The card was wrapped
      in cellophane, placed in the recess and then covered with pink auto polymerizing
      acrylic resin. On retrieval of the card from the denture, the entire data could
      be read as before without any distortion. The identification cards did not pose
      any problems in function and speech and were esthetically acceptable by the
      patients. 

PMID- 24293921
TI  - The incisive papilla: a significant landmark in prosthodontics.
AB  - Several investigators have studied the horizontal relationship between incisive
      papilla and maxillary central incisor and measured the papilla incisor distance
      in dentate subjects to extrapolate this distance as a guide to place maxillary
      central incisors in complete dentures. Based on this premise, incisive papilla is
      recognized as an important landmark in complete denture construction. Papilla
      incisor measurements were made either from the middle or posterior border of the
      papilla and certain ethnic and national norms have been recommended to set the
      central incisors in complete dentures. This study was done on Dravidian dentate
      subjects to relate incisive papilla to central incisors and canines and also to
      ascertain its shape. During its transition to the edentulous state, incisive
      papilla changes its shape consequent to remodeling of the alveolar bone, palatal
      mucosa and interdental papilla following extraction of central incisor teeth. It
      was found that the papilla in dentate is not always round but seen in several
      forms. In some it was a double papilla and in a few it was rudimentary. The
      center of the papilla also changes from its dentulous to edentulous state. The
      posterior border is a relatively stable landmark since it undergoes least change
      after extraction of anterior teeth. 

PMID- 24293922
TI  - A comparitive evaluation of the marginal adaptation of zirconium coping and
      nickel-chromium coping using shoulder finish line design: an invitro study.
AB  - Marginal adaptation is an important factor for long term clinical success of the
      restoration. This study aims to evaluate and compare the marginal adaptation of
      zirconium coping and nickel-chromium coping using the shoulder finish line
      design. For the purpose of this study 30 master dies were fabricated. A total of
      30 copings were fabricated in which 15 zirconia copings and 15 Ni-Cr copings were
      fabricated. The copings obtained were seated on the die and marginal discrepancy
      between the metal die and the copings were then measured with Scanning electron
      microscope at magnification of *50 and the findings were statistically analyzed.
      Mean and standard deviation values of marginal discrepancy of cervical margins of
      zirconia copings were 39.32 and 2.66 MUm and Ni-Cr copings were 129.98 and 2.57
      MUm. Higher mean marginal gap (MUm) is recorded in Ni-Cr copings compared to
      zirconia copings. The difference in mean marginal gap (MUm) between the two
      copings is found to be statistically significant (P < 0.001). Within the
      limitation of this study it was concluded that higher mean marginal gap (MUm) was
      recorded in Ni-Cr copings compared to zirconia copings. The difference in mean
      marginal gap (MUm) between the two copings is found to be statistically
      significant (P < 0.001). 

PMID- 24293923
TI  - A case of cleidocranial dysostosis: dilemma for a prosthodontist.
AB  - Cleidocranial dysostosis (CCD) is an uncommon, generalized skeletal disorder
      characterized by delayed ossification of the skull, aplastic or hypoplastic
      clavicles, and complex dental abnormalities such as retention of multiple
      deciduous teeth, impaction or delayed eruption of permanent teeth and presence of
      supernumerary teeth. This case report describes a 30-year old male patient of CCD
      with classical findings and the challenges faced in his prosthodontic
      rehabilitation. Conventional complete dentures following interim complete
      dentures therapy had to be given as all other treatment modalities were ruled out
      because of anatomic limitations. Despite the disadvantages of removable dentures
      the patient adapted admirably to them with significant improvement in self
      esteem. Though orthodontic and surgical correction may be the treatment of
      choice, the need to preserve the alveolar ridge could make fabrication of
      removable dentures in such patients, a viable option. 

PMID- 24293924
TI  - A New Approach for Management of Kennedy's Class I Condition Using Dental
      Implants: A Case Report.
AB  - Replacement of multiple missing teeth mainly in the Kennedy's class I and class
      II condition is a challenge for the clinician and the patient in terms of
      retention, masticatory efficiency, esthetics, comfort and importantly economics.
      Here, a case using implants in the distal denture bearing area with ball
      attachments and fabricating a cast partial denture over it utilizing the best of
      all benefits has been presented. 

PMID- 24293925
TI  - An innovative design of 2-piece saliva reservoir using precision attachment: a
      case report.
AB  - Standard head and neck radiotherapy results in serious, often irreversible damage
      to the major and minor salivary gland tissues. The resultant profound hypo
      salivation leads to serious oral health and functional problems that seriously
      affect oral health-related quality of life. Intra-oral devices with reservoirs
      have been developed that allow the release of saliva substitute into the mouth.
      This case report describes an innovative technique for incorporation of saliva
      reservoir in cast partial denture in patient with post irradiation xerostomia. 

PMID- 24293926
TI  - Poor oral Hygiene may be the Sole Cause of Oral Cancer.
AB  - PURPOSE: The purpose of this case-control study was to draw attention to the
      possibility that poor oral hygiene resulting from infrequent and inadequate use
      of chewing sticks might be the sole cause of oral cancer in 60 patients
      investigated in the maxillofacial units of two specialist hospitals in eastern
      Nigeria. METHODS: Sixty cases and 60 controls made up the study population. We
      matched them for age, gender, period of admission and study site. The interview
      of all the participants contained data on demographic factors, family history of
      cancer, tobacco habits, oral hygiene, dietary habits and use of alcohol. We took
      biopsies of the lesions for histo-pathological examination. We entered the
      collected data into Microsoft excel package and transported it to Stata for
      generation of statistical test. RESULT: Poor oral hygiene due to infrequent tooth
      brushing was associated with primary oral cancer in this patient sample. On the
      other hand, frequent tooth brushing was related to healthy status. CONCLUSION: In
      the absence of other known carcinogens, poor oral hygiene may be the single
      factor that caused oral cancer in these subjects. Research is needed to
      investigate the pathological mechanism that is associated with this risk factor.

PMID- 24293927
TI  - Standards of facial esthetics: an anthropometric study.
AB  - AIM: Anthropometry is an art and science used extensively for measuring the soft
      tissue proportions. While it is true that error is found in measurements of this
      kind, a great many trends of growth and development and therapy changes can be
      recorded with a significant degree of accuracy. OBJECTIVE: Facial proportion
      varies among the different ethnic groups and today, most of the available studies
      are done on western population. Hence an Anthropometric study was conducted in
      the local population. MATERIALS AND METHODS: The study was carried out with the
      aim of measuring the facial soft tissue proportion in the local population using
      anthropometry. Study was done using 100 subjects (50 males and 50 females) with
      Class I skeletal relationship and pleasing profile. Using standard anthropometric
      landmarks the various anthropometric measurements and facial proportional indices
      were determined (both horizontal and vertical) and were compared with that for
      North American Caucasians. RESULTS: The statistical analysis revealed significant
      differences in the facial proportion between the two populations.

PMID- 24293928
TI  - Role of Arthrocentesis in the Management of Acute Closed Lock of TM Joint: A
      Pilot study.
AB  - The following study was conducted in Meenakshi Ammal Dental College on 32
      patients. The objective of our study was to assess the efficacy of arthrocentesis
      for the management of acute closed lock of TMJ. All patients presented with a
      history of sudden and persistent difficulty in mouth opening and associated TMJ
      pain. A total of 27 female and 5 male patients were treated using arthrocentesis
      and lavage under local anesthesia. Patients were assessed for pain and jaw
      function using visual analogue scales, VAS I (Fig. 4b), VAS II (Fig. 4c),
      respectively and mouth opening MMO (Fig. 4a) for a period of 6 months. Our
      results showed satisfactory relief in pain and improved mouth opening in 30
      patients. The results proved that arthrocentesis is a very useful technique for
      treatment of acute closed lock of TMJ. However to arrive at a definitive
      conclusion a long term evaluation is required. 

PMID- 24293929
TI  - Evaluation of Neurosensory Changes in the Infraorbital Nerve following Zygomatic
      Fractures.
AB  - PURPOSE: To evaluate the incidence and recovery of persistent sensory
      disturbances of the infraorbital (IO) nerve after isolated zygomatic complex
      fractures with various treatment methods. METHODS AND RESULTS: The study was
      inclusive of isolated unilateral zygomatic complex fractures and fractures of IO
      rim .Tests performed were Pin prick and Electrical detection threshold test. The
      evaluation was done preoperatively, after 1 month and after 6 months of surgery.
      The results suggested that neurosensory disturbance was present in all the
      patients with zygomatic complex fractures. At 1 month post-operatively some
      sensory deficit was present in all the patients on the affected side. After 6
      months all the patients showed near to normal improvement comparable to normal
      side. CONCLUSION: Study shows that earlier the surgical intervention, more the
      recovery of the nerve injury is appreciable during the 1 and 6  months follow up
      period.

PMID- 24293930
TI  - Bio-resorbable plates as effective implant in paediatric mandibular fracture.
AB  - AIM: To evaluate the efficacy of bio-resorbable plates in paediatric mandibular
      fracture. MATERIALS AND METHODS: In the present study, 40 cases of mandibular
      fractures were treated by Inion Cps plating system using, 2 and 2.5 mm
      (LPLA/DLPLA/TMC/PGA) bio-resorbable bone plates and screws of 6 and 8 mm screws.
      The assessment of the patients was done at 2 week, 1, 3, and 6 months using the
      clinical parameters and bite force recording. RESULTS: There was significant
      reduction in pain at different follow-ups. Paraesthesia was found in two patients
      with body fracture which remained for 2 week and 1 month follow-up. No
      paraesthesia was found after 3rd follow-up. Significant stability of fracture
      fragments were found on different follow ups. Implant exposure was present only
      in two patients (5%) at 1 month follow up. There was significant increase in
      incisor, right molar and left molar bite force at 1, 3 and 6 months, from 2nd
      week onwards. CONCLUSION: These findings show that the use of bio-resorbable
      plates in paediatric mandibular fracture was efficacious enough to bear the
      masticatory loads during osteosynthesis of the fracture. The recent and
      significant achievement is the advent of bio-resorbable osteosynthesis devices
      that has almost solved the problems of stress shielding, secondary surgery and
      corrosion when metal implants are left-in situ.

PMID- 24293931
TI  - Safety of extracapsular dissection in benign superficial parotid lesions.
AB  - INTRODUCTION: The current practice for removal of clinically benign superficial
      parotid lesions is an appropriate superficial parotidectomy with a cuff of normal
      parotid tissue for complete pathological clearance. This technique requires the
      identification of the facial nerve at the main trunk and dissection of the
      segment of the facial nerve deep to the lesion. The reported major complications
      of this procedure include temporary or permanent facial nerve weakness, Frey's
      syndrome and salivary leaks. In order to avoid these complications, a local
      extracapsular dissection technique can be utilised in the management of small
      inferiorly located benign lesions of the parotid gland. METHODS: A retrospective
      case note review was performed for all parotidectomies between 2004 and 2009 in
      Addenbrooke's Hospital, Cambridge by the senior authors. RESULTS: A total of 172
      cases were identified out which 46 underwent an extracapsular dissection. The
      average size of these lesions was 1.9 cm (0.9-2.4 cm) with all universally
      located inferior or posterior to the angle of the mandible. The pathologies were
      14 pleomorphic adenomas, 24 Warthin's tumours, 6 lymphangiomas and 2 simple
      cysts. There were no post-operative facial nerve weaknesses, Frey's syndrome or
      salivary leaks within the extracapsular dissection group. The median follow-up of
      these patients were 4.6 years (2-6 years) with 6 patients lost to follow-up. No
      recurrences have been noted in the cohort at follow-up.

PMID- 24293932
TI  - Cutaneous sinuses of cervicofacial region: a clinical study of 200 cases.
AB  - PURPOSE: To evaluate the sinuses in the cervicofacial region and to identify the
      focus of infection. It is also to help the clinician in differentiating the
      sinuses' of odontogenic and nonodontogenic focus of infection. MATERIALS AND
      METHODS: The study has been conducted in 200 patients, aged between 11 and 77
      years for a period of 6 and a half years at Narayana Dental College and Hospital,
      Nellore. History of present illness, clinical, radiological and laboratory
      examinations were carried out on all the patients. RESULTS: Majority of the
      cervical sinuses are of odontogenic origin (80%) and non-odontogenic being (20%)
      of the cases. CONCLUSION: The literature reveals that many cases have been
      misdiagnosed and inappropriately treated by many specialties of Medicine and
      Surgery wherein the odontogenic foci of infection is the main etiological factor
      for cervicofacial sinuses. A proper diagnosis is important and forms a key to the
      successful management of these sinuses in the head and neck region.

PMID- 24293933
TI  - Versatility of Dieffenbach's Modification of Weber Fergusson's Approach for
      Treatment of Maxillary Pathologies.
AB  - OBJECTIVE: The aim of the study is to evaluate the usage of Dieffenbach's
      modification of Weber-Fergusons approach in the treatment of lesions involving
      maxilla. STUDY: In this study five different maxillary pathologies were
      approached through Dieffenbach's modification of Weber-Fergusons approach.
      Partial and subtotal procedures were performed depending on the type of pathology
      and the extent of the lesion which was assessed both clinically and
      radiologically. The study evaluates the easy exposure of the site, post operative
      complications like scar formation and infra orbital nerve parasthesia. RESULTS:
      There were two subtotal maxillectomy procedures and three partial maxillectomy
      procedures approached through Dieffenbach's modification of Weber-Fergusson's
      approach. All the cases recovered well in the post operative healing period
      without noticeable scarring. There was parasthesia in three cases which subsided
      in 3 months. CONCLUSION: The approach through Dieffenbach's modification of Weber
      Fergusons incision gave better visibility and accessibility to the lesions of
      maxilla. Because there is direct access to the pathology, the inadvertent
      resection of the un-involved structures is prevented thus minimizing the
      morbidity.

PMID- 24293934
TI  - Bear maul injuries in maxillofacial region: our experience.
AB  - Injuries due to bear mauling are rarely reported in the literature. Bears are
      strong and agile wild animals, potentially dangerous, unpredictable and can
      inflict serious injuries. Mammalian attack injuries have a special place in
      traumatology because of their high complication rate when compared with similar
      soft tissue wounds otherwise caused. Bites from attacking animals may lead to
      local infection, and wounds that are potentially contaminated with a variety of
      pathogens. The excellent blood supply of the face makes infection a rare
      occurrence, however, the injury may cause sufficient disfigurement to require
      extensive reconstruction. Treatment of mammalian bite wounds must address both
      the management of soft tissue deformities and then prevention of post treatment
      infection. Although generally considered to be dirty or contaminated they could
      be successfully treated by surgical cleansing and primary suture with a
      favourable outcome. The bony injuries also have to be addressed. Management of
      such injuries often need multidisciplinary approach and multiple secondary
      surgeries to treat the secondary defects. 

PMID- 24293935
TI  - Peripheral osteoma of the maxillofacial region diagnosis and management: a study
      of 06 cases.
AB  - BACKGROUND: Osteomas are benign neoplasm often associated with facial asymmetry,
      pain and surface ulceration. Peripheral osteomas are more common in the cranio
      maxillofacial region. It is prevalent at younger age but maximum seen in the
      sixth decade, with a female to male ratio is 1:2. The aim of this study was to
      review the clinical presentations and management protocol of such lesions in
      cranio-maxillofacial region. MATERIALS AND METHODS: The study was conducted at
      Command Military Dental Centre (EC) during May 2004 to May 2007. Six serving
      soldiers and their families (four males, two females), age group ranging between
      13 and 56 years, mean age 34.5 years were recruited in this study. The tumors
      were excised using extra oral, intra oral and combined approaches; no
      complications were reported during post op period. RESULTS: All the cases were
      operated under GA through extra oral, intra oral and combined approaches with
      satisfactory results. HPE report was benign in all our cases with no post
      operative complications reported during follow up. CONCLUSION: Cranio
      maxillofacial osteomas are exclusively benign tumors and not very common
      entities. Proper diagnosis and precision management alleviates symptoms without
      any post surgical complications. In our series of six cases the tumors were
      diagnosed and managed as per standard surgical protocol with excellent result.

PMID- 24293936
TI  - Platelet rich fibrin: a novel approach for osseous regeneration.
AB  - : To evaluate the efficacy of autologous platelet rich fibrin in soft tissue
      healing and bone regeneration in mandibular third molar extraction sockets.
      METHOD: The study was conducted in 20 patients visiting in outpatient department
      of Oral and Maxillofacial Surgery, requiring extraction of bilateral mandibular
      third molar, following extraction platelet rich fibrin (PRF) was placed in one
      extraction sockets, the other socket was studied as the control sites with no
      PRF. The patient were assessed for post operative pain, soft tissue healing and
      trabecular pattern in healing bone. Radiological assessment of the extraction
      site was done for period of 3 months to evaluate the change in bone density.
      RESULTS: Pain was less in study side compare to control site soft tissue was
      healing was better in study site. Evaluation of trabecular bone formation started
      earlier in PRF site compare to control site. The evaluation of bone density by
      radiological assessment showed the grey level value calculated after 3 months at
      the PRF site well comparatively higher than the average baseline value of the
      bone density at the extraction site in control site. CONCLUSION: The study showed
      that autologous PRF is biocompatible and has significantly improved soft tissue
      healing. Bone regeneration and increase in bone density in extraction sockets.
      However, a more elaborate study with a large number of clinical cases is
      essential to be more conclusive regarding its efficacy.

PMID- 24293937
TI  - Comparison of preauricular approach versus retromandibular approach in management
      of condylar fractures.
AB  - AIM: The aim of the study is to compare the two extra oral approaches to the TMJ
      viz preauricular and retromandibular approach in management of condylar fractures
      of mandible. METHODS AND MATERIALS: Patients with fractured dislocation and
      displacement of mandible condyle in medial direction were managed by preauricular
      approach. Patients with lateral displacement of mandibular condyle were managed
      by retromandibular approach. OPG, Reverse towne's, and C.T. scan were taken in
      all the cases prior to surgery to assess the pattern of displacement. RESULTS: In
      our study both approaches have given excellent access and visibility to the
      condylar fractures but with limitations in each technique. Minimal intraoperative
      and postoperative complications were encountered in both approaches. The duration
      of the procedure for preauricular approach was much longer when compared with
      retromandibular approach. Facial nerve weakness was common in patients treated
      with preauricular approach, which they improved over a period of time and had
      complete recovery. Postoperative scar was imperceptible in all cases and good
      cosmetic results were seen with both approaches. Mouth opening, mandibular
      movements and occlusion were more or less same in both the approaches while pain
      and clicking was common in preauricular approach. CONCLUSION: Both approaches
      have good results in managing condylar fractures with retromandibular approach
      having ease of access and ease of fixation. So one can always give preference to
      retromandibular approach over preauricular approach in managing the condylar
      fracture except in some cases where preauricular approach is the only option like
      anteromedial dislocation or complete medial dislocation of condylar segment.
      Situations, where patients who reported very late for the surgery with resultant
      scarring of the tissue, in those cases preauricular approach is the only option.

PMID- 24293938
TI  - A Comparative Evaluation of Fixation Techniques in Anterior Mandibular Fractures
      Using 2.0 mm Monocortical Titanium Miniplates Versus 2.4 mm Cortical Titanium Lag
      Screws.
AB  - OBJECTIVE: To compare the efficacy and surgical outcome of treatment of anterior
      mandibular fracture using either 2.0 mm titanium miniplate or 2.4 mm titanium lag
      screw technique. MATERIALS AND METHODS: A total of 30 patients were managed by
      open reduction and internal fixation utilizing the miniplate and lag screw
      technique for fractures of anterior mandible. The patients were randomly divided
      into two groups. Group I: (15 patients) were treated with Leibinger, 2.0 mm
      titanium mini plates system with self-tapping screws and Group II: (15 patients)
      were treated with 2.4 mm cortical lag screw (Synthes). Intraoperatively duration
      of surgery was measured from the time incision was placed till the closure of
      wound. Subsequent follow up was done at 3, 6, 12, 24 weeks, postoperatively.
      During every follow up, patients were assessed clinically for malocclusion,
      neurosensory deficit, biting efficiency, implant failure, mal-union/non-union.
      Pre and postoperative radiographs were taken to assess the gap between fracture
      segments. Results were evaluated using Chi square and the unpaired t test.
      RESULTS: In our study, the mean duration of surgery (hours) was 1.97 +/- 0.52 for
      group I and 1.26 +/- 0.55 for group II. The difference was found to be
      statistically significant (p value 0.001). i.e. more time was taken in case of
      surgery with mini-plates when compared to the lag screw. Short surgical procedure
      reduces the incidence of infectious complications, which significantly lowers the
      financial burden. The mean post-operative radiographic distance between all
      measuring points were considerably more in case of mini-plate group as compared
      to lag screw group. Lag screw group showed faster improvement in terms of biting
      efficiency as compared to mini-plate group which showed a tendency to masticate
      only medium hard food items by 24 weeks. In both groups, no postoperative
      malocclusion was noted. In initial weeks, neurosensory deficit was seen more in
      mini-plate group as compared to lag screw group but after six weeks all patients
      showed improvement in neurosensory function without any permanent nerve damage.
      CONCLUSION: According to this prospective study, rigid internal fixation provided
      by lag screw technique for anterior mandibular fracture offers several advantages
      over conventional bone plating. It is an excellent means of achieving rapid and
      safe fixation which is followed by primary bone healing in anterior mandibular
      fractures, without any major complications.

PMID- 24293939
TI  - Use of nasolabial flap in intra and extraoral reconstruction: our experience with
      40 cases.
AB  - PURPOSE: This article represents the use of inferiorly based nasolabial flap in
      reconstruction of various intraoral and extraoral defects. PATIENTS AND METHODS:
      Nasolabial flaps were performed in 40 patients, for reconstruction of buccal
      mucosa, gingivobuccal sulcus, commissure, lower lip, floor of mouth, upper lip
      and lower alveolar defects. RESULTS: The most common defect site in the oral
      cavity was the buccal mucosa. Partial flap necrosis occurred in five patients.
      Out of 40 cases of carcinoma of lip, commissure and floor of the mouth, all the
      patients had good speech after complete healing of the wound. None of the
      patients who had lip or commissure reconstruction developed drooling of saliva
      due to lip incompetence. CONCLUSION: The inferiorly based nasolabial flap
      provides reliable coverage of intermediate-sized oral cavity defects when used
      alone. Minimal donor morbidity is associated with its use. It is especially
      useful in elderly patients with facial skin laxity and where esthetics is not a
      major concern.

PMID- 24293940
TI  - Impacted Inverted Teeth with their Possible Treatment Protocols.
AB  - INTRODUCTION: Inversion of the impacted tooth is a rare condition. The purpose of
      this article is to review this rare condition in detail on the basis of available
      literature. In addition, this article also explores the various multidisciplinary
      approaches varying from space creation to prosthodontic rehabilitation and
      reimplantation to endodontic treatment for inverted impacted teeth. DISCUSSION: A
      very few cases of inverted and impacted third molars have been reported in the
      literature. We describe few rare cases of inverted impacted teeth which presented
      to us in the Dept. Of Oral Surgery, K.D. Dental College and Hospital over a
      period of 2 years approx. we report of four cases presented to us with inverted
      maxillary third molars (Figs. 1, 2), inverted supernumerary tooth in anterior
      maxilla (Figs. 3, 4). RESULT: The first and second case of maxillary third molar
      and third case, of supernumerary tooth, the patients presented were asymptomatic,
      hence patient opted for conservative management and continued follow up, in the
      fourth case, the supernumerary tooth was removed for orthodontic reasons.
      CONCLUSION: On the basis of literature available, it has been noticed that
      related complications particularly depend on justification on whether the tooth
      follicle is with a pathology or is pathology-free. Pathology-free and
      asymptomatic cases can be treated in a conservative manner. Possible treatment
      protocol for impacted inversion is entirely dependent on patient's needs,
      findings and surgeons skills.

PMID- 24293941
TI  - A study on dentigerous cystic changes with radiographically normal impacted
      mandibular third molars.
AB  - BACKGROUND: Dentigerous cyst develops in the follicular tissue surrounding the
      impacted lower third molar. A study was carried out to know the incidence of
      Association of Dentigerous cyst with radiographically normal impacted lower third
      molars and to draw the attention of the Oral Surgeons towards the prophylactic
      removal of impacted third molars. METHODS: A prospective study was done on 30
      patients with impacted lower third molars which were indicated for extraction.
      The follicle tissue surrounding the impacted tooth was subjected for
      histopathologic investigations. Only those teeth with a radiographic finding of
      pericoronal space of less than 2.5 mm were considered. Two Oral Pathologists
      reviewed the slides for any changes suggestive of cystic pathology. RESULTS:
      Pathologic changes suggestive of Dentigerous cyst was found in 7 of the 30
      follicular tissue sent for histopathologic testing. It was found to be
      statistically significant (P < 0.001). CONCLUSION: This study shows statistically
      high incidence of Dentigerous cyst association with radiographically normal
      impacted lower third molar teeth. Hence the Oral and Maxillofacial surgeons
      should consider histopathologic evaluation and radiographic diagnosis in the
      management of impacted lower third molars. Prophylactic extractions of normal
      impacted lower third molars should be considered as a treatment option.

PMID- 24293943
TI  - Functional and esthetic rehabilitation in a partially edentulous patient: a case
      report.
AB  - A young male patient reported with forwardly placed mandible and partially
      edentulous upper and lower jaws. Patient's chief concern was towards his abnormal
      facial profile and difficulty in mastication. This case report describes various
      procedures performed to rehabilitate the patient functionally and esthetically.
      The treatment plan included Onlay bone grafting of mandible using iliac crest,
      body osteotomy of edentulous mandible and implant retained overdenture. 

PMID- 24293942
TI  - Evolution and trends in reconstructive facial surgery: an update.
AB  - Surgical correction of congenital and acquired facial deformities has transcended
      the primitive era of using non biologic materials to current attempts at own face
      growing through biotechnology. A summative account of this trend is still lacking
      in the literature. The objective of this article is to present an update on
      current knowledge in the strides to achieve functionally and aesthetically
      perfect facial reconstruction. It highlights the impact of advancements in 3D
      imaging, stereolithographic biomodelling, microvascular surgical tissue
      transplantation and tissue biotechnology in the surgical efforts to solve the
      problems of facial disfigurement whether congenital or acquired. 

PMID- 24293944
TI  - A Large Sialolith Perforating the Wharton's Duct: Review of Literature and a Case
      Report.
AB  - Sialolithiasis accounts for the most common cause of diseases of salivary glands.
      The majority of sialoliths occur in the submandibular gland or the Wharton's
      duct. This article discusses review of literature, predisposing factors, signs
      and symptoms, diagnostic methods and various modalities available for the
      management of sialolithiasis. This case report presents a case of sialolith of a
      large size in the left Wharton's duct, which was explored and removed via an
      intra-oral approach. 

PMID- 24293945
TI  - Warthin's Tumor of Bilateral Parotid Glands: A Case Report.
AB  - Bilateral Warthin's tumours of parotid constitute a small proportion of all
      salivary gland tumours. We present a case report of surgical management of a
      prototype case. 

PMID- 24293946
TI  - Huge plunging ranula.

PMID- 24293947
TI  - Intraoral schwannoma in retromolar region.
AB  - Schwannomas of the intra oral region are relatively uncommon; these are benign
      nerve sheath tumors that arise from schwann cells of the neural sheath. They are
      solitary, slow-growing, smooth-surfaced, usually asymptomatic, and encapsulated
      tumors, about 25% of all schwannomas are located in the head and neck, but only
      1% show intraoral origin. We are contributing a report of 24 years old woman with
      slow progressive swelling over the right retromolar region. Magnetic resonance
      imaging presented a well defined mass over the right retromolar area measuring 19
      * 19 mm(2) and fine needle aspiration cytology revealed that it was a tumor mass
      of neurogenic origin. Diagnosis was confirmed by excisional histological
      identification of Antoni A areas with marked palisading of nuclei. Although these
      rare entities of oral cavity are routinely not encountered in practice, they
      should be added in differential diagnosis of intraoral tumors. 

PMID- 24293948
TI  - Bilateral transmigration of mandibular canines: a rare occurrence.
AB  - Transmigration is a phenomenon in which an unerupted tooth migrates and crosses
      the midline. Transmigration of the mandibular permanent canine is a rare
      phenomenon. We report a case of bilateral transmigrated mandibular canines, which
      presented as pain in the lower anterior teeth. 

PMID- 24293949
TI  - Extensor indicis proprius opponensplasty - the burkhalter revisited.
AB  - The Extensor Indicis Proprius Opponensplasty although not widely exercised by
      hand surgeons has previously been shown to produce good results in the
      restoration of thumb opposition. Over the last 5 years the Extensor Indicis
      Proprius was selectively used in cases where the Flexor Digitorum Superficialis
      was unavailable or inappropriate. In a small case series operating on a total of
      six male patients with an average age of 32 and follow up of 12 months we have
      been impressed by the functional outcome and lack of donor site morbidity. The
      Extensor Indicis Proprius is expendable with minimal donor site morbidity, is of
      sufficient length and has an optimal line of pull to provide a superior
      mechanical advantage and a favourable torque when compared to Flexor Digitorum
      Superficialis. 

PMID- 24293950
TI  - Comparison between external fixators and fixed-angle volar-locking plates in the
      treatment of distal radius fractures.
AB  - Distal radius fractures are a common disorder in industrialized nations
      associated with osteoporosis, with a reported incidence of two fractures per
      thousand patients per year. We performed a retrospective study comparing two sets
      of 40 patients, with fracture of the distal radius treated with Penning external
      fixator, compared to 40 patients treated with fixed-angle volar-locking plate
      (Plate Depuy (r) DVR), with the objective of finding differences between both
      treatment methods in anatomical values, functional outcomes and complication
      rates. All fractures were classified according to the AO classification. Postero
      anterior and lateral radiographs of the wrist were taken after fracture, after
      surgery and at 6 months after surgery. We also assessed functional outcome.
      Minimum follow up was of 10 months. We compared complications between both
      groups. In the group of patients treated with fixed-angle volar-locked plate,
      radiological results are found to be closer to the anatomical references. Final
      outcomes revealed similar functional scores between both groups. The
      complications rate was statistically higher in the group of patients who
      underwent external fixation. In the fixed-angle volar-locked plate group, most of
      complications were related to patient discomfort due to the volar-locking plate. 

PMID- 24293951
TI  - A cadaveric study of the first dorsal compartment of the wrist and its content
      tendons: anatomical variations in the Indian population.
AB  - de Quervain's disease is a commonly encountered problem; its management is
      multimodal, and often, there is recurrence which is commonly associated with
      anatomical variation in the first dorsal compartment of the wrist. Our purpose
      was to find out the anatomical variation of the first dorsal compartment of the
      wrist in the general population to assess the anatomical basis of de Quervain's
      disease and its recurrence. In this cadaveric study, 86 wrists in 46 patients
      were dissected to search out the first dorsal compartment of the wrist and its
      content tendons, presence of septa in the compartment, and insertion of the
      tendons. Supernumerary tendons in the first dorsal compartment were seen in 74.41
      % of cases. The most commonly found tendon arrangement was two abductor pollicis
      longus (APL) and one extensor pollicis brevis (EPB). In all cases, there was a
      fixed insertion of APL to the base of the first metacarpal. Among other sites,
      the most common site of insertion of APL is the trapezium, which was 56.14 %.
      Variations of EPB with respect to number, site of insertion, thickness, and
      bilaterality were also found. The presence of septations was found in 37.20 % of
      dissected cadaveric wrists. We had found supernumerary tendons or slips in the
      first dorsal compartment very commonly. The presence of a septum was less
      frequently found. So, it may be concluded that there is immense anatomical
      variation present in the first dorsal compartment of the wrist, supernumerary
      tendons/tendon slips are commonly found, there is a variation of insertions
      present in the population, septum/aberrant compartment are also present, and
      bilateral variations are present in the population. These variations may be
      responsible for recurrence and unilateral affection in de Quervain's disease. 

PMID- 24293952
TI  - The biomechanical and histological effects of diabetes on tendon healing:
      experimental study in rats.
AB  - The aim of this study was to investigate the biomechanical and histological
      perspectives of healing of Achilles tendon in diabetic rats and compare the
      results with non-diabetic subjects. Fifty four adult Wistar Albino rats weighing
      300-350 g were used throughout the study. Six animals were excluded from the
      study and replaced. Rats were randomly assigned to either the experimental or the
      control group comprised of 24 rats in each. Diabetes was induced in experimental
      group with streptozotocin. 3 days after the induction of diabetes, both Achilles
      tendons were transected 5 mm proximal to their insertions to the calcaneal bone
      and repaired by using 6/0 polypropylene sutures with modified Kessler method. At
      weeks 2, 4 and 6, eight rats from each group were euthanized. Left Achilles
      tendons including the repair site were prepared for histological evaluation and
      right legs were prepared for mechanical testing. When compared to control group,
      diabetic animals displayed a lower peak force for failure in each of the second,
      fourth and sixth week. The differences between the groups in each week were found
      to be significant in statistical assessments (p < 0.05). Histologic assessment
      revealed that the diabetic animals had significantly less amount of fibroblast
      proliferation and lymphocyte infiltration compared to the control group. There is
      significant delay in tendon strength at the end of week 2, 4 and 6
      postoperatively in the diabetic rats. Therefore diabetic individuals require
      specific postoperative follow up and rehabilitation procedures. 

PMID- 24293953
TI  - Rehabilitation regimens following surgical repair of extensor tendon injuries of
      the hand-a systematic review of controlled trials.
AB  - There is no consensus on the most effective rehabilitation regimen following
      extensor tendon repair of the hand. This systematic review evaluates the outcomes
      of the various regimens. The Cochrane, MEDLINE, EMBASE, CINAHL, AMED, PEDro,
      OTseeker databases were searched for any prospective randomised clinical trials
      comparing rehabilitation regimens for acute extensor tendon injuries in adults.
      Five papers met the inclusion criteria. The regimens were static immobilisation,
      dynamic splinting and early active motion (EAM). There was no standard format of
      reporting. The sample size ranged from 27 to 100 patients. The duration of follow
      up ranged from 8 to 24 weeks. Overall, patients' total active motion improved
      with time. Early mobilisation regimens (active and passive) achieve quicker
      recovery of motion than static immobilisation but the long-term outcome appears
      similar. Given the comparable outcomes between dynamic splinting and EAM, we
      therefore favour EAM which is simpler and more convenient. 

PMID- 24293954
TI  - Skin Prepping for Upper Limb Procedures: Should I Keep my Eyes Closed Doc?
AB  - Antiseptics containing alcohol are commonly used due to their effective
      antiseptic properties. However, they may cause eye irritation if splashed into
      the eyes in awake patients receiving regional anaesthesia. We present a simple
      technique to avoid such cases. 

PMID- 24293955
TI  - These Wire Cutters are Broken.
AB  - K-wire cutters have a fixed range of cutting capabilities. Wire cutters are most
      efficiently applied perpendicular to the K-wire as oblique application increases
      the effective diameter of the K-wire, which may cause the wire cutters to break. 

PMID- 24293956
TI  - Mixed Infections of the Paronychium with Prevotella bivia.

PMID- 24293957
TI  - Multiple osteochondroma of the hand in a 6 year old child- a case report.

PMID- 24293958
TI  - Triquetrohamate coalition with lunotriquetral and lunohamate osteoarthritis.

PMID- 24293959
TI  - Desk of the editor.

PMID- 24293960
TI  - Are We Over-treating Neck in Buccal & Alveolo-buccal Cancers: Experience from a
      Tertiary Cancer Care Center.
AB  - Oral cancer is one of the most common types of cancer seen in India with buccal
      and alveolo buccal regions being the most frequent subsites. A retrospective
      analysis of buccal and alveolo buccal cancer patients undergoing neck dissection
      from 1995 to 2009 was performed to analyze the profile of neck dissections and
      patterns of nodal involvement in these patients. Total 310 neck dissections were
      done for buccal and alveolo-buccal cancer including 41 (13.2 %) RND, 231(74.5 %)
      MND and 38 (12.2 %) Supraomohyoid neck dissection (SOHND). Clinically palpable
      nodes were present in 75.9 % patients but only 117 (38 %) were pathologically
      node positive. 20 % had occult positive nodes in N0 group. Level I was most
      commonly involved with 35 % having positive nodes in more than one level. There
      were no patients with isolated involvement of level IV or V with only 3.9 %
      patients with involvement of level III. Current guidelines recommend neck
      dissection in all clinically node positive patients. However, our experience
      shows that neck is over treated in majority of patients and there is a need to
      optimize surgical management of neck in these patients. 

PMID- 24293961
TI  - Acute abdomen as an unusual presentation of broad ligament angiomyolipoma. A case
      report and review of literature.

PMID- 24293962
TI  - Robotic right colon resection: evaluation of first 50 consecutive cases for
      malignant disease.

PMID- 24293963
TI  - Obesity, HDL and Breast Cancer.

PMID- 24293964
TI  - Current trends in breast surgery.
AB  - Breast surgery has evolved significantly over the last decade. This includes
      developments in pre-operative assessment of patients and surgical options offered
      to patients. Oncoplastic breast surgery has emerged as a new approach and uses
      plastic surgery techniques for reconstructing the wide local excision defect. 

PMID- 24293965
TI  - The Effect of Simultaneous Peripheral Excision in Breast Conservation upon Margin
      Status.

PMID- 24293966
TI  - Penile metastasis from carcinoma of caecum- unusual cause of priapism: a case
      report and review of literature.

PMID- 24293967
TI  - Preoperative radiotherapy in carcinoma rectum.
AB  - The present study was undertaken to address the various concerns that has limited
      the use of preoperative radiotherapy in rectal cancer in our institution. All
      patients diagnosed as having carcinoma rectum between August 2005 and July 2007
      were included in the study. Group 1 patients consisted of those presenting with
      T2, T3 and T4 who received preoperative radiation of 25 Gy. Group 2 consisted of
      those with T4 tumours, who received Long course radiotherapy. Complication of
      radiation like dermatitis, enteritis and proctitis were noted. Before surgery CT
      scan and TRUS were repeated. In the postoperative period a record of abdominal,
      perineal wound complications and other complications were noted. The results were
      compared with a similar group of patients who did not receive preoperative
      radiotherapy. There were 21 patients (12males) with a mean age of 48.4 years
      (Range 18-70) in the radiotherapy group. Sixteen patients received short course
      (25 Gy) and five patients received long course of preoperative radiotherapy.
      Fourteen patients underwent definitive surgery in the form of abdominoperineal
      resection (APR) or anterior resection (AR). In the non-RT group there were 17
      patients (8 males) with a mean age of 50.2 year. Fourteen patients underwent
      definitive surgery like APR (11) and AR (3). In the RT group CT scan and TRUS
      failed show any significant downsizing or down staging of tumour. In the RT
      group, incidence of acute skin toxicity was 23.8 % (5/21), all were seen in those
      who received long course of radiotherapy (Group 2). Grade 2 or 3 lower G I
      symptoms occurred in 3 (18.6 %) patients of Group 1 and 1(20 %) patient of group
      2. There was higher incidence of perineal wound complication in the RT group
      (19.0 % vs 5.9 %). Preoperative long course of radiotherapy may be associated
      with high rates of dermatitis and perineal wound infection. Short course may be
      associated with lower G I toxicity. 

PMID- 24293968
TI  - An unusual presentation of primary rib non hodgkins lymphoma masquerading as male
      breast cancer.

PMID- 24293969
TI  - Caecal gastrointestinal stromal tumor with perforation and obstruction.

PMID- 24293970
TI  - Rhabdomyosarcoma of biliary tract- a diagnostic dilemma.
AB  - Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor. It is a rare
      tumor in children but the most common cause of malignant obstructive jaundice in
      them. A 4-year-old child presented to us with obstructive jaundice and palpable
      liver. He was misdiagnosed as choledochal cyst on imaging studies; however,
      intraoperative and histopathological features confirmed the diagnosis of
      rhabdomyosarcoma. Mass excision and Roux en Y portoenterostomy was performed.
      Post operatively; the patient was put on multimodal chemotherapy. This, being an
      uncommon entity, is being reported with a review of the available literature. 

PMID- 24293971
TI  - Role of sentinel lymph node biopsy in early cervical cancer.

PMID- 24293972
TI  - Influence of margins on disease free survival following hepatic resection for
      colorectal metastasis: a meta-analysis.
AB  - The aim of our study was to conduct a meta-analysis of reports published on
      hepatic resection for colorectal liver metastases (CRLM) and determine if a
      negative margin >=1 cm confers a disease free survival (DFS) advantage over sub
      centimeter negative margins. The 357 initially selected articles were screened to
      identify 90 articles of interest of which eleven were finally included in the
      meta-analysis. Patients with positive margins were excluded from the meta
      analysis. Meta-analysis was performed using STATA 9.2 statistical software. A
      total of 1,989 patients with negative margins from the eleven studies were
      included in the meta-analysis. The 5-year DFS for all patients was 27.9 % (95 %
      CI 23.5 % to 32.2 %). The 5-year DFS for >=1 cm negative margin subgroup was 34.4
      % (95 % CI 27.97 % to 40.7 %) when compared to 21.0 % (95 % CI 17.4 % to 24.7 %)
      for <1 cm negative margin subgroup. The odds ratio for >=1 cm negative margins
      was found to be 0.552 (95 % CI 0.408 to 0.747, p < 0.001) when compared to <1 cm
      negative margins. The results of this meta-analysis demonstrate that in patients
      undergoing hepatic resection for CRLM, a negative margin >= 1 cm may confer a
      better DFS compared with a sub-centimeter negative margin. 

PMID- 24293973
TI  - Metastatic squamous cell carcinoma of colon presenting as a parietal abscess.
AB  - Metastatic squamous cell carcinoma of the gastrointestinal tract is relatively
      uncommon. It is associated with a poor prognosis and behaves more aggressively.
      We report a case of metastatic growth in the ascending flexure of the colon that
      had eroded into the anterior abdominal wall muscles and resulted in a large
      parietal abscess. She had undergone radical hysterectomy followed by radiation
      therapy for stage II carcinoma of the uterine cervix 14 months back. Ultrasound
      guided drainage of the abscess was done as an emergency procedure to control the
      sepsis. After 3 days an extended Right Hemicolectomy with stapled ileo colic
      anastomosis was done with resection of a part of abdominal wall adherent to the
      growth with a grossly normal margin. Histopathological examination confirmed
      metastatic squamous cell carcinoma. She is disease free 2 months after surgery.
      Surgical management of the metastatic tumour was palliative but necessary to
      prevent intestinal obstruction in future. 

PMID- 24293974
TI  - Nutritional status and nutritional support before and after pancreatectomy for
      pancreatic cancer and chronic pancreatitis.
AB  - Cachexia, malnutrition, significant weight loss, and reduction in food intake due
      to anorexia represent the most important pathophysiological consequences of
      pancreatic cancer. Pathophysiological consequences result also from
      pancreatectomy, the type and severity of which differ significantly and depend on
      the type of the operation performed. Nutritional intervention, either parenteral
      or enteral, needs to be seen as a method of support in pancreatic cancer patients
      aiming at the maintenance of the nutritional and functional status and the
      prevention or attenuation of cachexia. Oral nutrition could reduce complications
      while restoring quality of life. Enteral nutrition in the post-operative period
      could also reduce infective complications. The evidence for immune-enhanced feed
      in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported
      by the available clinical data. Nutritional support during the post-operative
      period on a cyclical basis is preferred because it is associated with low
      incidence of gastric stasis. Postoperative total parenteral nutrition is
      indicated only to those patients who are unable to be fed orally or enterally.
      Thus nutritional deficiency is a relatively widesoread and constant finding
      suggesting that we must optimise the nutritional status both before and after
      surgery. 

PMID- 24293975
TI  - A review of the role of anticoagulation in the treatment of peripheral arterial
      disease.
AB  - Peripheral arterial disease (PAD) is a major medical/surgical problem associated
      with high risk for coronary heart disease (CHD). Anticoagulation plays a
      significant role in the management of the PAD patient. However, evidence-based
      medicine supports only select anticoagulants, mainly antiplatelet agents. The
      available anticoagulant classes, their individual medications, and the mechanisms
      of action are described. Dextran 40, platelet glycoprotein (GP) IIb/IIIa receptor
      antagonists, direct thrombin (factor IIa, FIIa) inhibitors, and factor Xa (FXa)
      inhibitors do not, at this juncture, appear to have a significant role to play in
      the PAD patient. Aspirin has been used in PAD patients for a few decades, as has
      warfarin, but the role of warfarin is very limited. An attempt has been made to
      place each medication and its function in context all the way to the present with
      oral direct thrombin (FIIa) and FXa inhibitors described. These inhibitors may
      ultimately play an, as yet, undefined role in PAD. Specific use of anticoagulants
      in PAD patients is described and aspirin still stands out as a fundamental
      therapy. The thienopyridines, especially clopidogrel, have their established
      place and there is some evidence for benefit from the use of clopidogrel in dual
      therapy with aspirin. Dipyridamole, especially with aspirin as dual therapy, and
      cilostazol also have their evidence-based niches. The main role played by
      warfarin is for the patient with a vein graft in the arterial circulation.
      Heparin retains significant procedural importance. For now, Class I, Level of
      Evidence A center around aspirin for the PAD patient with clopidogrel, an
      alternative agent. 

PMID- 24293976
TI  - No effect of clopidogrel activity or cessation on vascular function or markers of
      inflammation.
AB  - The platelet adenosine diphosphate (ADP)-receptor blocker clopidogrel is
      effective in reducing the rate of thrombosis in cardiovascular disease, but may
      also have nonplatelet activity. However, there is variability in the suppression
      of platelet function in individuals, leading to the concept of clopidogrel
      resistance, that is, reduced platelet-suppressing activity. We tested the
      hypothesis that some of the beneficial effect of clopidogrel may be due to the
      variable activity of this drug on the vascular system (assessed by plasma markers
      von Willebrand factor and soluble E-selectin, and functional arterial pulse wave
      velocity) and inflammation (C-reactive protein and interleukin-6) while 32
      patients with coronary artery disease taking 75 mg clopidogrel daily, and again 2
      weeks after cessation of clopidogrel therapy. Platelet responsiveness to
      clopidogrel was assessed by the phosphorylation of intracellular regulatory
      protein-vasodilator-stimulated phosphoprotein method and aggregometry to ADP.
      Response to aspirin was assessed using arachidonic acid (AA), and soluble P
      selectin and PAC-1 were also measured. While on clopidogrel, there were no
      relationships between any vascular or inflammatory index and the response to
      clopidogrel. After stopping clopidogrel, there were no differences in platelet
      aggregation to AA, or the expression of P-selectin or PAC-1 at rest, or after
      stimulation by AA, but platelet responses to ADP all increased (p < 0.01).
      Although soluble P-selectin increased when clopidogrel was stopped (p = 0.006),
      there were no changes in plasma markers or vascular function. We conclude that 75
      mg/day clopidogrel has no effect of markers of vascular function or inflammation.

PMID- 24293977
TI  - Treatment of varicose veins by transilluminated powered phlebectomy surgery: a 9
      year experience.
AB  - Transilluminated powered phlebectomy (TIPP) is a minimally invasive technique for
      varicose vein removal that addresses some limitations of traditional procedures.
      The study objective was to analyze perioperative and follow-up outcomes after
      TIPP and present modifications gleaned over 9 years of performing the technique.
      Four hundred and thirty-one patients who underwent TIPP performed between June
      2002 and April 2011 were included in this retrospective review. Descriptive
      statistics were used to describe demographic, treatment, and outcome data. The
      mean procedure time was 20.2 minutes. The majority (50.5%) of cases involved 10
      to 20 incisions. No significant varicosities were reported at a follow-up of 12
      weeks. Postoperative complications included 2 (0.5%) deep vein thromboses, 8
      (1.9%) cellulitis episodes, 16 (3.7%) hemosiderin staining cases, 2 (0.5%)
      abscesses, and 2 (0.5%) cases of excessive or hypertrophic scarring. All but one
      patient reported good outcomes and were satisfied with the procedure. With proper
      training and experience, TIPP with a lower oscillation frequency and secondary
      tumescence results in good outcome and high patient satisfaction. 

PMID- 24293978
TI  - Variability in carotid endarterectomy at a single medical center: an outcome and
      cost analysis.
AB  - Carotid endarterectomy (CEA) is a common surgical procedure. Its efficacy in the
      prevention of stroke has been proven by multiple clinical trials including North
      American Symptomatic Carotid Endarterectomy Trial and Asymptomatic Carotid
      Atherosclerosis Study. Currently, there is a wide variability in the technique of
      this operation. This study was performed to determine the variability of CEA at
      the University of Kentucky Medical Center with a focus on cost and short-term
      outcome. We reviewed the charts of a consecutive series of 349 patients
      undergoing CEA at our institution. We analyzed the variability in shunt used
      across surgeons, intraoperative variables, cost, and outcome. Data on 374
      procedures on 349 patients who underwent CEA showed shunt utilization varied
      significantly by surgeon from 3 to 94%. Patch utilization also varied
      significantly by surgeon. Two in-hospital deaths occurred in the shunt group
      (1.3%) and none in the no-shunt group. Shunt placement was associated with 1 hour
      24 minutes increase in operative time from 2 hours 3 minutes in the no-shunt
      group to 3 hours 27 minutes in the shunt group (t test, p < 0.01). Shunt
      placement was associated with a 1.74-day increase in length of stay, from 2.97
      days in the no-shunt group to 4.71 days in the shunt group. There was no
      significant difference in the cost of procedure in these two groups: no-shunt
      $11,510 +/- $3,977, shunt group $11,479 +/- $4,030. This study showed no
      significant difference in cost or outcome between various techniques. 

PMID- 24293979
TI  - Screening of diabetic foot in surgical inpatients: a hospital-based study in
      saudi arabia.
AB  - Previous reports found that identification of diabetic patients at high risk of
      foot ulcers, and managing the risk factors early, lower extremity amputations
      could be prevented. The aim of this study is to determine the value of screening
      diabetics in estimating the risk of foot ulceration among surgical inpatients.
      This is a prospective study on all diabetic patients admitted to the surgical
      department, King Fahd Hospital of the University, Saudi Arabia, during the year
      2011. Patients were screened for the presence of diabetic foot. They were
      classified according to the international working group on the diabetic foot into
      four grades [0 (lowest risk patients), 1, 2, 3 (highest risk patients)]. During
      the study period, 391 patients had diabetes mellitus (DM), of these 73 (19%) had
      active ulcer and were excluded from the study and the rest were screened. Grade 0
      was in 174 (54.5%) patients, the rest were grades 1, 2, and 3. There was
      significant difference between low-risk groups (grades 0, 1) and high-risk groups
      (grades 2, 3) as regards age, smoking and duration of DM. This study indicates
      that prevalence of diabetic patients with risk of foot ulceration in surgical
      inpatients was high. Routine screening of diabetic foot is recommended specially
      in old patients. 

PMID- 24293980
TI  - Associated venous injury significantly complicates presentation, management, and
      outcomes of axillosubclavian arterial trauma.
AB  - Axillosubclavian vessel injury (ASVI) is associated with high morbidity and
      mortality. Most studies are single-center experiences of small numbers of
      patients with penetrating injury. We assessed 21st-century presentation and
      management of ASVI and focused on outcomes of combined arterial/venous injury. We
      reviewed the National Trauma Data Bank for patients with isolated arterial ASVI
      (group 1) and combined arterial/venous ASVI (group 2). Demographics, injury
      severity parameters, interventions, complications, and outcomes were compared. We
      identified 581 patients with ASVI (mean age 35.1; 88.1% male), with 466 isolated
      arterial injuries and 115 combined arterial/venous injuries. Group 2 had lower
      presenting systolic blood pressure and Glasgow Coma Scale, and had higher rates
      of operative repair (55.7 vs. 43.1%, p = 0.016) and higher mortality (33.9 vs.
      13.9%, p < 0.001). There were no differences in amputation (5.2 vs. 2.4%, p =
      0.121), compartment syndrome (2.6 vs. 1.9%, p = 0.713), and deep vein thrombosis
      (0.9 vs. 0.2%, p = 0.357). When separated by mechanism of injury, combined
      injuries from blunt trauma did increase amputation rates (27.8 vs. 4.2%, p =
      0.002). Multivariate analysis revealed that combined arterial/venous injury
      significantly increased risk of death (odds ratio [OR], 2.99; confidence interval
      [CI], 1.73 to 5.17; p = 0.0001). Penetrating injury had higher odds of death than
      blunt injury (OR, 1.96; CI, 1.03 to 3.73; p = 0.041). ASVI is rare but extremely
      lethal. Concomitant venous and arterial injury is not associated with worse limb
      related outcomes, except in blunt injuries and resultant amputations, but is
      associated with a threefold increase in mortality rates compared with isolated
      arterial injury. 

PMID- 24293981
TI  - Looking for a Learning Curve in EVAR Based on the Zenith Stent Graft.
AB  - The purpose of this study was to report the learning curve of endovascular
      aneurysm repair (EVAR) based on the Zenith stent graft (Cook Medical Inc.,
      Bloomington, IN). In the last 9 years, 101 patients were treated with a Zenith
      stent graft. To display the learning curve, a cumulative sum (CUSUM) failure
      analysis curve of the 30-day technical success rate was calculated. For detailed
      analysis, our EVAR patient cohort was chronologically divided into three groups.
      Technical and clinical results, basic patient parameters, and procedural data
      were compared. The CUSUM graph indicated an initial sharp rise within the first
      35 cases and a plateau thereafter. The 30-day technical success rate
      significantly increased from the first to the second group (83 vs. 100%; p =
      0.019), as did the primary technical success rate (66 vs. 97%; p = 0.001). EVAR
      based on the Zenith stent graft required ~35 cases to reach a stably high rate of
      short-term technical success. 

PMID- 24293982
TI  - Very Late Development of Coronary Artery Aneurysm with Total Occlusion following
      Sirolimus-Eluting Stent Implantation.
AB  - A 41-year-old African American woman presented with chest pain and was found to
      have non-ST segment elevation myocardial infarction with a peak cardiac troponin
      I of 28.5. Elective cardiac catheterization revealed a 70% ostial left anterior
      descending (LAD) artery stenosis. The patient underwent percutaneous coronary
      intervention and a sirolimus-eluting stent (Cypher, Miami, FL, 3.5 * 8 mm) was
      successfully deployed. Three years after stent implantation, the patient
      presented with recurrent angina. Repeat coronary angiography revealed a large
      aneurysm involving the proximal portion of the stent with a total occlusion at
      the mid to distal portion of the stent with collaterals to LAD from left
      circumflex artery. The patient underwent coronary artery bypass surgery with left
      internal mammary artery graft to LAD and ligation of LAD at its origin proximal
      to the aneurysm. 

PMID- 24293983
TI  - Klippel-trenaunay syndrome: an often overlooked risk factor for venous
      thromboembolic disease.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital condition redefined by Oduber et
      al (2008) by the coexistence of vascular malformations and disturbed soft tissue
      or bony growth, including hypertrophy or hypotrophy in the same or opposite sides
      of the body. The anomalies may involve part of a limb, a whole limb, a limb
      girdle, or a hemibody. Vascular malformations may involve veins, capillaries, or
      lymphatics although venous or capillary malformations are essential for the
      diagnosis. Associated venous anomalies include dysplasia, valvular malformations,
      and varicosities. Congenital venous anomalies are often associated with
      disturbances of blood flow and should be considered as prothrombotic states.
      However, such anomalies are not considered in Wells scores and used to determine
      the risk for venous thromboembolism (VTE). We present the case of a male with
      unrecognized crossed dissociated form of KTS and unsuspected VTE. The
      pathophysiology and the treatment of VTE in KTS are discussed. We suggest
      physicians to be aware of KTS and that its recognition in a critically ill
      patient should prompt consideration for appropriate prophylaxis for high-risk
      category for VTE. Dedicated duplex sonography should be obtained if VTE is
      suspected. We also suggest a modification of the Wells scores to reflect the
      association of KTS and VTE. 

PMID- 24293984
TI  - Embolization of an Aberrant Right Subclavian Artery Aneurysm with Amplatzer
      Vascular Plug without Bypass.
AB  - Aberrant right subclavian artery (ARSA) aneurysms are rare, but the risk of
      rupture and thromboembolism is high, with a postrupture mortality rate of 50%.
      Open surgical repair of ARSA aneurysms usually requires thoracotomy and aortic
      grafting, which can be contraindicated in high-risk patients with multiple
      comorbidities. Endovascular repair of ARSA aneurysms has been reported, with or
      without adjunctive surgical bypass. We report a case of an 80-year-old woman
      resenting with an asymptomatic 4 cm ARSA aneurysm who underwent a completely
      endovascular treatment of the aneurysm using an Amplatzer vascular plug II (St.
      Jude Medical Inc., St. Paul, MN). 

PMID- 24293985
TI  - Broken guidewire fragment.
AB  - Advances in technology and greater operator experience have increased the success
      rate of percutaneous coronary intervention while lowering the complication rates.
      The broken guidewire is a rare complication of percutaneous coronary
      intervention. We present this rare complication in a patient who was medically
      treated. 

PMID- 24293986
TI  - Toward uniformity in reporting of thoracic aortic diameter.

PMID- 24293987
TI  - "Internal Mammary Vein Cannulation during Port-o-Cath Insertion".

PMID- 24293988
TI  - Hierarchical Adaptive Regression Kernels for Regression with Functional
      Predictors.
AB  - We propose a new method for regression using a parsimonious and scientifically
      interpretable representation of functional predictors. Our approach is designed
      for data that exhibit features such as spikes, dips, and plateaus whose
      frequency, location, size, and shape varies stochastically across subjects. We
      propose Bayesian inference of the joint functional and exposure models, and give
      a method for efficient computation. We contrast our approach with existing state
      of-the-art methods for regression with functional predictors, and show that our
      method is more effective and efficient for data that include features occurring
      at varying locations. We apply our methodology to a large and complex dataset
      from the Sleep Heart Health Study, to quantify the association between sleep
      characteristics and health outcomes. Software and technical appendices are
      provided in online supplemental materials.

PMID- 24293989
TI  - Case report of a neonate with ocular toxoplasmosis due to congenital infection:
      estimation of the percentage of ocular toxoplasmosis in Greece caused by
      congenital or acquired infection.
AB  - We report a case of a newborn male child with congenital toxoplasmosis. During
      pregnancy seroconversion occurred and positive titers of antitoxoplasmic
      antibodies (immunoglobulin M and G) were found in the mother, in the third
      trimester. She received treatment with spiramycin. After birth, the neonate
      presented with chorioretinitis and intracranial calcifications. The neonate
      received treatment with pyrimethamine, sulfadiazine, and leucovorin for 1 year.
      In addition to using a previously described method, we report for the first time
      in Greece an estimation regarding the percentage of ocular toxoplasmosis caused
      by congenital or acquired infection. We estimate that ocular toxoplasmosis in
      Greece is caused in 7% of the cases by congenital infection, and in 93% of the
      cases by acquired infection. 

PMID- 24293990
TI  - Central retinal artery occlusion in association with fibromuscular dysplasia.
AB  - A 14 year-old female, whose chief complaint was severe vision loss in the right
      eye for 2 days, presented to the Clinic of Ophthalmology of Fatih Sultan Mehmet
      Education and Research Hospital. The patient had been attending follow-up visits
      for 4 years, following a diagnosis of fibromuscular dysplasia by the Clinic of
      Pediatrics. The patient underwent a complete ophthalmo-logic, angiographic,
      hematologic, and systemic evaluation. Fundus fluorescein angiography was
      performed immediately, because of the cherry-red spot sign in the macula of the
      right eye. Fundus fluorescein angiography revealed evidence of marked stasis of
      the retinal arterial circulation in the right eye. Best corrected visual acuity
      was 20/400 in the right eye and 20/20 in the left eye. 

PMID- 24293991
TI  - Preferences for oral versus intravenous adjuvant chemotherapy among early breast
      cancer patients.
AB  - PURPOSE: The purpose of this study was to evaluate preferences for oral versus
      intravenous adjuvant chemotherapy among early breast cancer patients (UMIN-CTR
      number UMIN000004696). PATIENTS AND METHODS: Eighty-two postmenopausal women with
      estrogen receptor-positive, human epidermal growth-factor receptor 2-negative
      breast cancer who had completed adjuvant chemotherapy were asked about their
      preferred route of administration of chemotherapy and the reason. Women also
      answered questions about their physical and psychological status and quality of
      life during chemotherapy. RESULTS: Patients who had received oral chemotherapy
      preferred it more frequently than those who had received intravenous chemotherapy
      (100% versus 37%, respectively, chi-square =15.5; P<0.001). Patients who
      preferred the same route of administration of chemotherapy as they had previously
      received showed a significantly better psychological status during chemotherapy
      compared with those who preferred a different route. CONCLUSION: Our study showed
      that preferences for oral and intravenous chemotherapy strongly depended on the
      actual prior administration of chemotherapy and patients' own experiences during
      chemotherapy.

PMID- 24293992
TI  - Epidemiology of non-fatal cerebrovascular stroke and transient ischemic attacks
      in Al Quseir, Egypt.
AB  - BACKGROUND AND PURPOSE: Stroke is a medical emergency that can cause permanent
      neurological damage, complications, and disability. We aim to determine the
      epidemiology of non-fatal cerebrovascular stroke (CVS) and transient ischemic
      attacks (TIAs) in Al Quseir City, Red Sea, Egypt. METHODS: The total population
      (n=33,285) was screened through a door to door study by three specialists of
      neurology and 15 female social workers (for demographic data collection). All
      suspected stroke patients were subjected to a full clinical examination,
      computerized tomography (CT) and/or magnetic resonance imaging (MRI) of their
      brain, blood sugar, lipogram, serum uric acid, complete blood cells, blood urea,
      and serum creatinine, as well as evaluated by Barthel Index and Scandinavian
      Stroke Scale. Carotid doppler, echocardiography, and thyroid functions were done
      for selected cases. RESULTS: CVS was recorded among 130 patients out of 19,848
      subjects aged 20 years and more, yielding a total prevalence of 6.55/1,000
      population. From June 1, 2010 to May 31, 2011, 36 patients were recorded to have
      stroke within 1-year, yielding an incidence rate of 1.81/1,000. Prevalence and
      incidence rates were higher among males than females, and both indices increased
      steadily with advancing age to reach the highest prevalence (37.02/1,000) and
      incidence rate (9.5/1,000) among aged persons 60 years and more. CONCLUSION: The
      prevalence of non-fatal stroke in Al Quseir city (6.55/1,000) was at the lower
      range of that recorded in developing countries (5-10/1,000) and slightly higher
      than that recorded in industrialized countries (5/1,000 population). Ischemic
      stroke is the most common type of stroke. The prevalence of TIAs was 0.15/1,000.

PMID- 24293993
TI  - Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and
      oxidative stress in COPD patients.
AB  - BACKGROUND: Previous studies have demonstrated the potential beneficial effect of
      N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD). However,
      the required dose and responder phenotype remain unclear. The current study
      investigated the effect of high-dose NAC on airway geometry, inflammation, and
      oxidative stress in COPD patients. Novel functional respiratory imaging methods
      combining multislice computed tomography images and computer-based flow
      simulations were used with high sensitivity for detecting changes induced by the
      therapy. METHODS: Twelve patients with Global Initiative for Chronic Obstructive
      Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo
      daily for 3 months and were then crossed over to the alternative treatment for a
      further 3 months. RESULTS: Significant correlations were found between image
      based resistance values and glutathione levels after treatment with NAC (P =
      0.011) and glutathione peroxidase at baseline (P = 0.036). Image-based resistance
      values appeared to be a good predictor for glutathione peroxidase levels after
      NAC (P = 0.02), changes in glutathione peroxidase levels (P = 0.035), and
      reduction in lobar functional residual capacity levels (P = 0.00084). In the
      limited set of responders to NAC therapy, the changes in airway resistance were
      in the same order as changes induced by budesonide/formoterol. CONCLUSION: A
      combination of glutathione, glutathione peroxidase, and imaging parameters could
      potentially be used to phenotype COPD patients who would benefit from addition of
      NAC to their current therapy. The findings of this small pilot study need to be
      confirmed in a larger pivotal trial.

PMID- 24293994
TI  - Noninvasive positive pressure ventilation in subjects with stable COPD: a
      randomized trial.
AB  - BACKGROUND: The use of domiciliary noninvasive positive pressure ventilation
      (NPPV) in stable chronic obstructive pulmonary disease (COPD) with chronic
      hypercapnic respiratory failure has yielded variable effects on survival, quality
      of life, and dyspnea. We hypothesized that use of NPPV in stable COPD and partial
      pressure of carbon dioxide (PaCO2) <52 mmHg might result in improvement in
      quality of life and dyspnea. METHODS: Thirty patients with stable COPD (forced
      expiratory volume in the first second <50% predicted and PaCO2 <52 mmHg) were
      prospectively randomized to receive domiciliary NPPV (bilevel positive airway
      pressure, 15/5 cm H2O) or usual therapy for 6 months. Measurements were made at
      baseline, 6 weeks, 3 months, and 6 months. Primary outcomes were quality of life
      as assessed by the Chronic Respiratory Disease Questionnaire (CRQ), and dyspnea
      as measured by the Transitional Dyspnea Index (TDI). RESULTS: Fifteen subjects in
      the NPPV arm and 12 controls completed all the study visits. At 6 weeks and 3
      months, the NPPV arm showed significant improvement in TDI total score. However,
      this effect persisted only in the TDI-Task at 6 months (P=0.03). NPPV use was
      associated with a small improvement in the CRQ-Mastery domain (0.6 versus -0.1,
      P=0.04). The arterial partial pressure of oxygen (PaO2) in the control arm
      worsened over the period of the study, whereas it remained stable in the NPPV arm
      (change -7.2 mmHg versus +2.1 mmHg, respectively, P=0.02). CONCLUSION: NPPV
      resulted in a small improvement in quality of life indices in stable COPD
      patients with PaCO2 <52 mmHg. Future larger studies will clarify the role of NPPV
      in this stable subgroup of patients with COPD.

PMID- 24293995
TI  - Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular
      hypertrophy.
AB  - BACKGROUND: The electrocardiographic diagnostic dyad of emphysema, namely a
      combination of the frontal vertical P-vector and a narrow QRS duration, can serve
      as a quasidiagnostic marker for emphysema, with specificity close to 100%. We
      postulated that the presence of left ventricular hypertrophy in emphysema may
      affect the sensitivity of this electrocardiographic criterion given that left
      ventricular hypertrophy generates prominent left ventricular forces and may
      increase the QRS duration. METHODS: We reviewed the electrocardiograms and
      echocardiograms for 73 patients with emphysema. The patients were divided into
      two groups based on the presence or absence of echocardiographic evidence of left
      ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume
      in one second (FEV1) were computed and compared between the two subgroups.
      RESULTS: There was no statistically significant difference in qualitative lung
      function (FEV1) between the subgroups. There was no statistically significant
      difference in mean P-vector between the subgroups. The mean QRS duration was
      significantly longer in patients with left ventricular hypertrophy as compared
      with those without left ventricular hypertrophy. CONCLUSION: The presence of left
      ventricular hypertrophy may not affect the sensitivity of the P-vector
      verticalization when used as a lone criterion for diagnosing emphysema. However,
      the presence of left ventricular hypertrophy may significantly reduce the
      sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it
      causes a widening of the QRS duration.

PMID- 24293996
TI  - Development and characterization of an injectable cement of nano calcium
      deficient hydroxyapatite/multi(amino acid) copolymer/calcium sulfate hemihydrate
      for bone repair.
AB  - A novel injectable bone cement was developed by integration of nano calcium
      deficient hydroxyapatite/multi(amino acid) copolymer (n-CDHA/MAC) and calcium
      sulfate hemihydrate (CSH; CaSO4 . 1/2H2O). The structure, setting time, and
      compressive strength of the cement were investigated. The results showed that the
      cement with a liquid to powder ratio of 0.8 mL/g exhibited good injectability and
      appropriate setting time and mechanical properties. In vitro cell studies
      indicated that MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite spread
      well and showed a good proliferation state. The alkaline phosphatase activity of
      the MC3T3-E1 cells cultured on the n-CDHA/MAC/CSH composite was significantly
      higher than that of the cells on pure CSH at 4 and 7 days of culture. The n
      CDHA/MAC/CSH cement was implanted into critical size defects of the femoral
      condyle in rabbits to evaluate its biocompatibility and osteogenesis in vivo.
      Radiological and histological results indicated that introduction of the n
      CDHA/MAC into CSH enhanced new bone formation, and the n-CDHA/MAC/CSH cement
      exhibited good biocompatibility and degradability. In conclusion, the injectable
      n-CDHA/MAC/CSH composite cement has a significant clinical advantage over pure
      CSH cement, and may be a promising bone graft substitute for the treatment of
      bone defects. 

PMID- 24293998
TI  - Synthesis, characterization, and antimicrobial properties of copper
      nanoparticles.
AB  - Copper nanoparticle synthesis has been gaining attention due to its availability.
      However, factors such as agglomeration and rapid oxidation have made it a
      difficult research area. In the present work, pure copper nanoparticles were
      prepared in the presence of a chitosan stabilizer through chemical means. The
      purity of the nanoparticles was authenticated using different characterization
      techniques, including ultraviolet visible spectroscopy, transmission electron
      microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and field
      emission scanning electron microscopy. The antibacterial as well as antifungal
      activity of the nanoparticles were investigated using several microorganisms of
      interest, including methicillin-resistant Staphylococcus aureus, Bacillus
      subtilis, Pseudomonas aeruginosa, Salmonella choleraesuis, and Candida albicans.
      The effect of a chitosan medium on growth of the microorganism was studied, and
      this was found to influence growth rate. The size of the copper nanoparticles
      obtained was in the range of 2-350 nm, depending on the concentration of the
      chitosan stabilizer. 

PMID- 24293997
TI  - Reducing the risk of infection associated with vascular access devices through
      nanotechnology: a perspective.
AB  - Intravascular catheter-related infections are still a major problem in health
      care and are associated with significant morbidity, mortality, and additional
      cost. The formation of microbial biofilm on catheters makes these infections
      particularly complicated, as microbial cells that detach from the biofilm can
      lead to infection, and because these microorganisms are highly resistant to many
      antimicrobial agents; thus, catheter removal is often required to successfully
      treat infection. To reduce the risks of catheter-related infections, many
      strategies have been applied, such as improvements in aseptic insertion and post
      insertion care practices, implantation techniques, and antibiotic coated or
      impregnated materials. However, despite significant advances in using these
      methods, it has not been possible to completely eradicate biofilm infections.
      Currently, nanotechnology approaches seem to be among the most promising for
      preventing biofilm formation and resultant catheter-related bloodstream infection
      (especially with multi-resistant bacterial strains). In this review, current
      knowledge about catheter technology and design, the mechanisms of catheter
      related bloodstream infection, and the insertion and care practices performed by
      medical staff, are discussed, along with novel, achievable approaches to
      infection prevention, based on nanotechnology. 

PMID- 24293999
TI  - Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal
      nanoparticles inhibit tumor growth in lung cancer.
AB  - MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the
      expression of target genes by posttranscriptional repression. miRs are
      dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic
      miR, is downregulated in lung cancers. Our earlier studies demonstrated that let
      7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be
      a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2)
      tyrosine kinase is overexpressed in most cancer cells, including MPM and non
      small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2
      receptor, inhibits cell proliferation and migration. In this study, to enhance
      the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3
      dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG
      (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was
      conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells.
      The LNP with an average diameter of 100 nm showed high stability, low
      cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1.
      The ephrin-A1 conjugated LNP (ephrin-A1-LNP) and let-7a miR encapsulated LNP (miR
      LNP) showed improved transfection efficiency against MPM and NSCLC. The
      effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1
      conjugated LNP (miR-ephrin-A1-LNP) was determined on MPM and NSCLC tumor growth
      in vitro. miR-ephrin-A1-LNP significantly increased the delivery of let-7a miR in
      lung cancer cells when compared with free let-7a miR. In addition, the expression
      of target gene Ras was significantly repressed following miR-ephrin-A1-LNP
      treatment. Furthermore, the miR-ephrin-A1-LNP complex significantly inhibited MPM
      and NSCLC proliferation, migration, and tumor growth. Our results demonstrate
      that the engineered miR-ephrin-A1-LNP complex is an effective carrier for the
      targeted delivery of small RNA molecules to lung cancer cells. This could be a
      potential therapeutic approach against tumors overexpressing the EphA2 receptor. 

PMID- 24294000
TI  - Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced
      oxidative stress and inflammation.
AB  - BACKGROUND: Cerium oxide nanoparticles (nanoceria) are effective at quenching
      reactive oxygen species (ROS) in cell culture and animal models. Although
      nanoceria reportedly deposit in lungs, their efficacy in conferring lung
      protection during oxidative stress remains unexplored. Thus, the study evaluated
      the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia.
      METHODS: A total of 48 animals were randomly divided into four equal groups
      (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus
      hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5
      MUg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H
      groups) for 5 weeks. After the final dose, H and T+H animals were challenged with
      hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were
      isolated and homogenate was obtained for analysis of ROS, lipid peroxidation,
      glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma
      was used for estimating major inflammatory cytokines using enzyme-linked
      immunosorbent assay. Intact lung tissues were fixed and both transmission
      electron microscopy and histopathological examinations were carried out
      separately for detecting internalization of nanoparticles as well as altered lung
      morphology. RESULTS: Spherical nanoceria of 7-10 nm diameter were synthesized
      using a microemulsion method, and the lung protective efficacy of the nanoceria
      evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of
      low micromole concentration, we successfully localized the nanoceria in rodent
      lung without any inflammatory response. The lung-deposited nanoceria limited ROS
      formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative
      protein modifications like nitration and carbonyl formation during hypobaric
      hypoxia. We also observed reduced lung inflammation in the nanoceria-injected
      lungs, supporting the anti-inflammatory properties of nanoceria. CONCLUSION:
      Cumulatively, these results suggest nanoceria deposit in lungs, confer protection
      by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any
      inflammatory response.

PMID- 24294001
TI  - Duloxetine in panic disorder with somatic gastric pain.
AB  - PANIC DISORDER IS THE MOST COMMON TYPE OF ANXIETY DISORDER, AND ITS MOST COMMON
      EXPRESSION IS PANIC ATTACKS CHARACTERIZED WITH SUDDEN ATTACKS OF ANXIETY WITH
      NUMEROUS SYMPTOMS, INCLUDING PALPITATIONS, TACHYCARDIA, TACHYPNEA, NAUSEA, AND
      VERTIGO: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic
      symptoms. In clinical practice, panic disorder manifests with isolated
      gastroenteric or cardiovascular symptoms, requiring additional clinical visits
      after psychiatric intervention. The first-line treatment for anxiety disorders,
      and in particular for panic disorder, is the selective serotonin reuptake
      inhibitors. However, these drugs can have adverse effects, including sexual
      dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic
      for some patients. Here we report the case of a 29-year-old Caucasian woman
      affected by panic disorder with agoraphobia who was referred to our clinic for
      recurrent gastroenteric panic symptoms. The patient reported improvement in her
      anxiety symptoms and panic attacks while on a selective serotonin reuptake
      inhibitor, but not in her gastric somatic problems, so the decision was taken to
      start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6
      months of treatment, the patient achieved complete remission of her gastric and
      panic-related symptoms, and was able to stop triple gastric therapy. Other
      authors have hypothesized and confirmed that duloxetine has greater initial
      noradrenergic effects than venlafaxine and is effective in patients with panic
      disorder. This case report underscores the possibility of tailoring therapeutic
      strategies for the gastroenteric expression of panic disorder. 

PMID- 24294002
TI  - Asperger syndrome related suicidal behavior: two case studies.
AB  - Asperger syndrome hinders adaptation to developmental challenges during childhood
      and adolescence, particularly with regard to interpersonal relationships.
      Individuals with Asperger syndrome display lack of empathy and limited ability to
      understand social and emotional exchanges with other people. Individuals with
      Asperger syndrome are significantly exposed to the risk of suicidal behavior,
      especially during adolescence. The authors describe cases of suicidal behavior in
      two adolescent boys with Asperger syndrome. 

PMID- 24294003
TI  - Visceral obesity is not an independent risk factor of mortality in subjects over
      65 years.
AB  - The aim of the study was to determine the role of obesity evaluated by body mass
      index (BMI), waist circumference (WC), and their combined effect on all-cause
      mortality according to age and related risk factors. This study included 119,090
      subjects (79,325 men and 39,765 women), aged from 17 years to 85 years, who had a
      general health checkup at the Centre d'Investigations Preventives et Cliniques,
      Paris, France. The mean follow-up was 5.6+/-2.4 years. The prevalence of obesity,
      defined by WC and BMI categories, was determined according to age groups (<55, 55
      65, >65 years). All-cause mortality according to obesity and age was determined
      using Cox regression analysis, adjusted for related risk factors and previous
      cardiovascular events. For the entire population, WC adjusted for BMI, an index
      of central obesity, was strongly associated with mortality, even after adjustment
      for hypertension, dyslipidemia, and diabetes. The prevalence of obesity increased
      with age, notably when defined by WC. Nonetheless, the association between WC
      adjusted for BMI and mortality was not observed in subjects>65 years old (hazard
      ratio [HR]=1.010, P=NS) but was found in subjects<55 (HR=1.030, P<0.0001) and 55
      65 years old (HR=1.023, P<0.05). By contrast, hypertension (HR=1.31, P<0.05),
      previous cardiovascular events (HR=1.98, P<0.05), and smoking (HR=1.33, P<0.05)
      remained associated with mortality even after age 65. In conclusion, WC adjusted
      for BMI is strongly and independently associated with all-cause mortality before
      65 years of age, after taking into account the associated risk factors. This
      relationship disappears in subjects>65 years of age, suggesting a differential
      impact of visceral fat deposition according to age.

PMID- 24294004
TI  - Body mass index and patient CT measurements as a predictor of benefit of
      intensity-modulated radiotherapy to the supraclavicular fossa.
AB  - BACKGROUND: Irradiation of the supraclavicular fossa is commonly used as part of
      adjuvant breast radiotherapy. Intensity-modulated radiotherapy (IMRT) may be used
      to target this region accurately, and there are subgroups of patients that may
      benefit more from IMRT than others. We identify the benefit of IMRT over fixed
      depth dose prescription to the supraclavicular fossa in patients of different
      builds in a clinical setting. METHODS: Fifteen patients who received radiotherapy
      to the left breast and supraclavicular fossa were selected. Computed tomographic
      planning was used to generate plans for supraclavicular fossa coverage. Dose
      prescription to 1.5 cm and 3.0 cm depths was compared with IMRT plans. Coverage
      of the planning target volume and dose to the organs at risk were compared and
      correlated with patient body mass index (BMI) and computed tomography
      measurements. RESULTS: Within the IMRT group, increasing depth of the
      supraclavicular fossa produced significantly better coverage of the planning
      target volume with IMRT. IMRT resulted in lower mean doses to the brachial plexus
      (P = 0.00) when compared with 1.5 cm and 3 cm depth dose prescriptions, but
      higher maximum brachial plexus doses. IMRT was more beneficial in patients with
      lower BMI because this resulted in a decreased maximum brachial plexus dose (P
      values of 0.03 and 0.001 when compared with 1.5 cm and 3.0 cm depth dose
      prescriptions, respectively). Higher patient BMI resulted in a lower dose
      contribution of IMRT to the cord (P-values 0.066 and 0.034 when compared with 1.5
      cm and 3.0 cm depth dose prescriptions respectively). CONCLUSION: IMRT of the
      supraclavicular fossa results in lower brachial plexus doses for patients with
      low BMI while patients with higher BMI benefit from lower mean cord doses. IMRT
      provides superior coverage of the planning target volume, especially in patients
      with a deeper supraclavicular fossa.

PMID- 24294005
TI  - Features and outcomes of lupus nephritis in Morocco: analysis of 114 patients.
AB  - BACKGROUND: There is wide variation in clinical presentation and outcome of lupus
      nephritis (LN) among different ethnic groups. Few data for LN exist on North
      Africans, especially those from Morocco. The aim of our study was to review
      retrospectively the features and outcome of LN in Moroccan patients. PATIENTS AND
      METHODS: We performed a single-center retrospective study. A total of 114
      patients with LN were included. All patients met American Rheumatism Association
      criteria. LN was classified according to the International Society of
      Nephrology/Renal Pathology Society classification. We adopted previously defined
      outcome criteria for LN. RESULTS: There were 101 females and 13 males, with a
      mean age of 29.9 years. At first presentation, we noted hypertension in 33%,
      hematuria in 76%, nephrotic syndrome in 53%, and renal failure in 60% of cases.
      Renal biopsy revealed predominant proliferative classes in more than 80% of
      patients. Patients received different regimens mainly based on intravenous
      cyclophosphamide. After a mean follow-up of 22 months, remission occurred in
      45.5%, relapses in 82%, end-stage renal failure in 21%, and death in 16% of
      cases. Infection and neurological and cardiovascular diseases were the most
      frequent causes of death. CONCLUSION: LN seems to be severe in our study, with a
      predominance of proliferative forms, severe renal manifestations, and poor renal
      and overall survival.

PMID- 24294006
TI  - Neuropathic pain and cytokines: current perspectives.
AB  - Neuropathic pain represents a major problem in clinical medicine because it
      causes debilitating suffering and is largely resistant to currently available
      analgesics. A characteristic of neuropathic pain is abnormal response to somatic
      sensory stimulation. Thus, patients suffering peripheral neuropathies may
      experience pain caused by stimuli which are normally nonpainful, such as simple
      touching of the skin or by changes in temperature, as well as exaggerated
      responses to noxious stimuli. Convincing evidence suggests that this
      hypersensitivity is the result of pain remaining centralized. In particular, at
      the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons
      is increased and neurons begin to be activated by innocuous inputs. In recent
      years, it has become appreciated that a remote damage in the peripheral nervous
      system results in neuronal plasticity and changes in microglial and astrocyte
      activity, as well as infiltration of macrophages and T cells, which all
      contribute to central sensitization. Specifically, the release of pronociceptive
      factors such as cytokines and chemokines from neurons and non-neuronal cells can
      sensitize neurons of the first pain synapse. In this article we review the
      current evidence for the role of cytokines in mediating spinal neuron-non
      neuronal cell communication in neuropathic pain mechanisms following peripheral
      nerve injury. Specific and selective control of cytokine-mediated neuronal-glia
      interactions results in attenuation of the hypersensitivity to both noxious and
      innocuous stimuli observed in neuropathic pain models, and may represent an
      avenue for future therapeutic intervention. 

PMID- 24294008
TI  - Managing and monitoring tuberculosis using web-based tools in combination with
      traditional approaches.
AB  - Tuberculosis (TB) remains a global health emergency. Ongoing challenges include
      the coordination of national and international control programs, high levels of
      drug resistance in many parts of the world, and availability of accurate and
      rapid diagnostic tests. The increasing availability and reliability of Internet
      access throughout both affluent and resource-limited countries brings new
      opportunities to improve TB management and control through the integration of web
      based technologies with traditional approaches. In this review, we explore
      current and potential future use of web-based tools in the areas of TB diagnosis,
      treatment, epidemiology, service monitoring, and teaching and training. 

PMID- 24294007
TI  - Personalized treatment for advanced colorectal cancer: KRAS and beyond.
AB  - Targeted therapies have improved the survival of patients with advanced
      colorectal cancer (CRC). However, further improvements in patient outcomes may be
      gained by the development of predictive biomarkers in order to select individuals
      who are most likely to benefit from treatment, thus personalizing treatment.
      Using the epidermal growth-factor receptor (EGFR) pathway, we discuss the
      existing and potential predictive biomarkers in clinical development for use with
      EGFR-targeted agents in metastatic CRC. The data and technological issues
      surrounding such biomarkers as expression of EGFR or its family members or
      ligands, KRAS-, NRAS-, and BRAF-mutation status, PI3K/PTEN expression, and
      imaging and clinical biomarkers, such as rash and hypomagnesemia, are summarized.
      Although the discovery of KRAS mutations has improved patient selection for EGFR
      targeted treatments, further biomarkers are required, especially for those
      patients who exhibit KRAS mutations rather than the wild-type gene. 

PMID- 24294009
TI  - Prevalence and risk factors for postpartum depressive symptoms in Argentina: a
      cross-sectional study.
AB  - INTRODUCTION: Postpartum depression is a prevalent disorder with negative
      consequences for women, infants, and the family as a whole. Most studies of this
      disorder have been conducted in Western countries, and studies from developing
      countries are few. In this paper, we report the first - as far as we are aware -
      study of the prevalence and risk factors associated with postpartum depressive
      symptoms in Argentina. MATERIALS AND METHODS: The study participants were 86
      women attending 6 week checkups, (range 4-12 weeks) postpartum at a private
      health care center in the metropolitan area of Buenos Aires. The women completed
      the Edinburgh Postnatal Depression Scale (EPDS) and a questionnaire collecting
      demographic and obstetric data. Data were described as proportions (percentages).
      Differences between proportions were assessed with chi-squared tests. To control
      for possible confounders, we fitted bivariate logistic regression models in which
      the dependent variable was an EPDS sum score of <10 versus a score of >=10.
      RESULTS: We found a high prevalence of depressive symptoms. A total of 32 women
      (37.2%) had an EPDS score of >=10, 16 (18.6%) had a score between 10 and 12, and
      16 (18.6%) had a score of >=13. In our sample, an EPDS score of >=10 was
      significantly associated with multiparity (odds ratio [OR] =3.58; 95% confidence
      interval [CI]: 1.13-11.30; P=0.030), pregnancy complications (OR =3.40; 95% CI:
      1.03-11.26; P=0.045), labor complications (OR =11.43; 95% CI: 1.71-76.61;
      P=0.012), cesarean section (OR =4.19; 95% CI: 1.10-16.01; P=0.036), and
      incomplete breast-feeding (OR =5.00; 95% CI: 1.42-17.54; P=0.012). CONCLUSION:
      Our results indicate that postpartum depression may be prevalent in Argentina,
      and may be associated with incomplete breast-feeding, cesarean section, perinatal
      complications and multiparity. The prevalence and risk factors for postpartum
      depression has not been described previously and is a considerable health-related
      problem among women. Argentinian health professionals should be aware of the high
      prevalence rate and possible risk factors so that these women and families can be
      identified and receive adequate support and treatment.

PMID- 24294010
TI  - Acute liver failure caused by mushroom poisoning: a case report and review of the
      literature.
AB  - It is estimated that there are over 5,000 species of mushrooms worldwide. Some of
      them are edible and some are poisonous due to containing significant toxins. In
      more than 95% of mushroom toxicity cases, poisoning occurs as a result of
      misidentification of the mushroom by an amateur mushroom hunter. The severity of
      mushroom poisoning may vary, depending on the geographic location where the
      mushroom is grown, growth conditions, the amount of toxin delivered, and the
      genetic characteristics of the mushroom. Amanita phalloides is the most common
      and fatal cause of mushroom poisoning. This mushroom contains amanitins, which
      are powerful hepatotoxins that inhibit RNA polymerase II in liver. Mushroom
      poisoning is a relatively rare cause of acute liver failure. A 63-year-old male
      patient was admitted to the emergency room with weakness, nausea, vomiting, and
      diarrhea. He reported ingesting several wild mushrooms about 36 hours earlier. In
      this article we report a case of lethal Amanita phalloides intoxication from
      stored mushrooms. 

PMID- 24294011
TI  - Erratum: Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic
      model [Corrigendum].
AB  - [This corrects the article on p. 153 in vol. 5, PMID: 24106429.].

PMID- 24294012
TI  - Will an increased supply of undertrained, under-resourced surgeons solve our wait
      list problems?

PMID- 24294013
TI  - An analysis of quantitative measurements of drainage exudate using negative
      suction in 96 microtia ear reconstructions.
AB  - Negative suction drainage is commonly used for the prevention of seromas or
      hematomas in auricular reconstruction surgery; however, there are few reports
      regarding the quantitative measurement of negative suction and its relation to
      disposed time, patient age or microtia type. In the present study, the authors
      recorded the volume of suction exudate in microtia reconstruction and elaborate
      on the relevant details of controlling negative suction. A negative suction
      drainage system was applied in 96 microtia patients between 2007 and 2010. Two
      small polyethylene drains were inserted adjacent to the concha and the scapha,
      respectively. The volume of exudate was recorded for three days after surgery and
      was analyzed according to disposed time, patient age and microtia type. The
      drains were removed on the third postoperative day, when only a small amount of
      exudate remained. A significant change in drainage was observed over three days
      postoperatively, and the quantity decreased progressively on the third
      postoperative day. Comparison of age groups showed that the volume of drainage
      from adults was greater than that from children or adolescents in the first two
      postoperative days, regardless of whether the drains were inserted in the scapha
      or concha. No statistical differences were found on the third postoperative day.
      A comparison of drain types revealed no statistically significant differences
      between scapha and concha drains three days postoperatively. The analysis
      demonstrated that drainage quantity is related to disposed time and patient age,
      but not to microtia type. The authors recommend removal of suction drains on the
      third postoperative day. Moreover, individualized negative suction treatment
      according to age or microtia type provides a safe and consistent approach to
      achieving acceptable results and fewer complications. 

PMID- 24294014
TI  - Short-term vasculoprotective effects of imatinib mesylate on intimal hyperplasia
      of arterial anastomosis: An experimental study using a rabbit model.
AB  - BACKGROUND: Since the beginning of the 'microvascular era', the success rates of
      microvascular procedures have increased to more than 90% in most series. The main
      reason for failure, however, is the healing of microarterial anastomosis, which
      is dependent on the status of endothelial cells and affects the rate of arterial
      thrombosis. In 80% of arterial thrombosis cases, complications are primarily
      observed during the first 72 h after surgery. Healing of arterial anastomosis
      results in intimal hyperplasia in which myofibroblasts comprise the predominant
      cell type. Intimal hyperplasia has been described previously as an adaptive
      process that occurs in response to hemodynamic stress or injuries to the vascular
      bed. During wound healing, fibroblasts proliferate, migrate and differentiate
      into myofibroblasts - a process that takes one to three days. Imatinib mesylate
      (ST1571-Gleevec, Novartis, Germany) is a specific platelet-derived growth factor
      receptor blocker that has found use as an adjunct to sirolimus in cardiovascular
      surgery for restenosis. However, its potential utility in preventing arterial
      thrombosis in microvascular surgery has not been evaluated in routine plastic
      surgery practice. METHODS: Twenty-four randomly selected, male, white New Zealand
      rabbits were divided into six groups (A to F), and the femoral artery model was
      used for arterial anastomosis. Following anastomosis, groups A, B and C received
      phosphate-buffered saline orogastrically. In groups D, E and F, imatinib mesylate
      was administered via an orogastric tube twice per day at a dose of 10 mg/kg
      starting two days before arterial anastomosis. Following anastomosis, imatinib
      mesylate was administered for one, three and seven days, and the regression of
      intimal hyperplasia was recorded. RESULTS: In groups administered imatinib
      mesylate (ie, groups D, E and F), intimal hyperplasia decreased by up to 50%,
      which represented a statistically significant difference. Histological analysis
      confirmed smooth muscle cell migration from the tunica intima to media on days 3
      and 7 in groups E and F. CONCLUSION: The present study revealed that imatinib
      mesylate, which was initiated as a prophylactic, systemic pretreatment and
      continued for seven days, gradually decreased intimal hyperplasia at the
      anastomosis site.

PMID- 24294015
TI  - Plastic surgery wait times in Ontario: A potential surrogate for workforce
      demand.
AB  - BACKGROUND: Accurate projections of plastic surgeon workforce requirements are
      essential to ensure a high standard of care and to properly allocate health care
      resources. Wait-time data were used to identify geographical areas that may
      benefit from additional plastic surgeons. METHODS: Plastic surgery wait times
      were analyzed using data from Ontario's Wait Time Information System for 2009 to
      2010. Data were compared with benchmarks published by the Canadian Society of
      Plastic Surgeons, and plastic surgeon density was captured by the Ontario
      Physician Human Resources Data Centre. RESULTS: Aggregate plastic surgery wait
      times at the 90th percentile failed to meet targets based on priority. For
      priority 2 (target = 28 days) and priority 3 cases (target = 84 days), wait times
      were 35 and 101 days, respectively (P<0.05). Wait times also consistently
      exceeded provincial standards in the southwestern (Local Health Integration
      Network [LHIN] 2), eastern (LHINs 10 and 11) and northeastern (LHIN 13) regions
      of Ontario. A negative correlation (r=-0.37; P<0.05) between wait times and
      surgeon density for priority 4 cases was observed, suggesting that more surgeons
      per capita is associated with shorter wait times for these lower-priority cases.
      In contrast, a positive correlation was observed for priority 2 (r=0.50; P<0.05)
      and priority 3 cases (r=0.35; P<0.05). CONCLUSION: Plastic surgery wait times in
      Ontario exceeded benchmarks in several geographical regions. Paradoxically, for
      high-priority cases, wait times were longer in LHINs with a higher density of
      plastic surgeons. Further investigation into patient mobility, physician practice
      patterns and the availability of hospital resources, such as hospital beds or
      operating room time, is required.

PMID- 24294016
TI  - Iatrogenic comminution of the phalangeal head during reduction or fixation of
      phalangeal neck fractures.
AB  - INTRODUCTION: Iatrogenic comminution of the phalangeal head during management of
      phalangeal neck fractures has not been previously investigated. OBJECTIVE: To
      investigate the causes and outcomes of this particular iatrogenic complication.
      METHODS: A database of phalangeal neck fractures over a six-year period (2006 to
      2011) was reviewed for this iatrogenic complication. Special attention was
      devoted to documenting the cause and pattern of comminution of the phalangeal
      head, as well as the outcome in range of motion. RESULTS: Of 152 cases treated
      during the study period, there were five (two children and three adults) with
      comminution. Two patterns of comminution were encountered: splitting and
      fragmentation of the phalangeal head. The complication occurred during open
      reduction and K-wire fixation, or during closed reduction in the emergency room.
      The outcome was generally poor and worse in patients with fragmentation of the
      entire head. Two of the five cases ultimately resulted in medicolegal claims.
      CONCLUSION: Comminution of the phalangeal head is a serious iatrogenic
      complication that may occur during the management of phalangeal neck fractures.
      Awareness of this complication is important and attempts should be made to avoid
      it.

PMID- 24294017
TI  - The effects of transcutaneous electrical nerve stimulation on tissue repair: A
      literature review.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) consists of a
      generic application of low-frequency, pulsed electrical currents transmitted by
      electrodes through the skin surface. It is a therapeutic modality that is
      nonpharmacological, noninvasive, inexpensive, easy to use and widely applied in
      clinical practice. OBJECTIVE: To narratively review the scientific evidence of
      the effects of TENS on tissue repair with respect to wound healing, skin flap
      viability and tendinous repair. METHODS: The study was conducted using the
      MEDLINE, Lilacs and Scielo databases, without limit to the period of publication,
      and was completed in November 2011. Inclusion criteria were randomized or
      nonrandomized, controlled or noncontrolled clinical trials, and experimental
      trials involving rats subjected to TENS for tissue repair. RESULTS: Thirty
      articles on tissue repair were found and, among these, 14 reported on wound
      healing, 14 reported on skin flaps and two analyzed tedinous repair. DISCUSSION:
      It was suggested that TENS stimulates skin wound healing and tendon repair, as
      well as the viability of random skin flaps. Such effects may be due to the
      release of substance P and calcitonin gene-related peptide, which would increase
      blood flow and, consequently, hasten the events leading to tissue repair.
      CONCLUSIONS: Based on the scientific evidence regarding the effects of TENS on
      tissue repair, the findings of the present literature review were inconclusive
      because data from the randomized controlled clinical trials were insufficient to
      confirm such effects.

PMID- 24294018
TI  - Treatment of vaginal agenesis using a modified McIndoe technique: Long-term
      follow-up of 23 patients and a literature review.
AB  - BACKGROUND: Congenital vaginal agenesis is a rare malformation with an incidence
      of one in 4000 to 5000 female newborns. The purpose of vaginal agenesis treatment
      is not only to create an adequate passageway for penetration but also to
      facilitate satisfactory sexual intercourse. OBJECTIVE: To present the results of
      a modified McIndoe technique with respect to sexual function, vaginal length and
      complication rates in patients with vaginal agenesis. METHODS: Between 2002 and
      2010, 23 patients with vaginal agenesis were admitted to the Gynecology Clinic of
      Istanbul University School of Medicine (Istanbul, Turkey) for vaginal
      reconstruction. All patients underwent a modified McIndoe procedure. The long
      term results with a follow-up period ranging from 18 to 118 months are presented.
      RESULTS: The postoperative mean vaginal length was 8.4 cm (range 6 cm to 11 cm)
      in 19 patients who used the mould regularly. Among 14 patients who used the mould
      regularly and had partners, only one experienced severe pain during intercourse
      and 13 reported that they were engaging in satisfactory sexual activity with mild
      or no pain, and with good mucosal sensitivity. Conversely, two of three patients
      who used the mould irregularly experienced severe pain during intercourse and had
      a mean vaginal length of 6 cm (range 4 cm to 8 cm). CONCLUSION: The findings
      suggest that a modified McIndoe technique is a simple, effective procedure for
      the treatment of vaginal agenesis; however, proper mould use after surgery
      remains the cornerstone of the treatment.

PMID- 24294019
TI  - Challenges and strategies for determining workforce requirements in plastic
      surgery.
AB  - BACKGROUND: Accurate projections of the future plastic surgeon workforce are
      essential to provide a high standard of care and to properly allocate scarce
      health care resources. This is not a straightforward task. Longstanding concerns
      over physician surpluses have been replaced by fears of physician shortages.
      METHODS: A review of previous efforts to predict future plastic surgeon workforce
      requirements highlights the challenges associated with deriving a solution.
      Physician workforce is dependent on numerous factors, including both physician
      supply factors, such as practice patterns and age, and population-demand factors
      including disease burden and socioeconomic factors. Factors unique to plastic
      surgery, such as overlap with other specialties and performance of uninsured
      services, must also be considered. Previous strategies from other areas of
      medicine are described with associated strengths and weaknesses. These strategies
      include needs- and demand-based approaches, economic analysis and benchmarking.
      Finally, the need for appropriate outcomes from which to assess adequacy of
      physician supply is discussed. CONCLUSIONS: Projections of future plastic surgeon
      workforce requirements must not only consider a multitude of physician supply and
      population demand factors, but also factors unique to plastic surgery. Future
      strategies to predict workforce requirements should balance the strengths and
      weaknesses of each approach with the data and outcomes available in plastic
      surgery.

PMID- 24294020
TI  - Postoperative management of Dupuytren's disease with topical nitroglycerin.
AB  - Dupuytren's contracture remains a significant clinical challenge due to
      associated complications and a recurrence rate of up to 60%. Commonly, the
      operated skin tends to rebuild scar in the area of surgery. Assuming local
      ischemia as an etiological factor, two cases in which topical nitroglycerin was
      used following surgical treatment of Dupuytren's disease are presented. In these
      patients, no raised scar formation developed during healing. At least six months
      after surgery, disease recurrence was not noted and the patients and surgeon
      reported improved skin quality. In the present study, the use of topical
      nitroglycerin, a local vasodilator, appeared to prevent recurrent scar formation,
      possibly through prevention of local ischemia. Further study and follow-up is
      necessary. 

PMID- 24294021
TI  - Forehead reconstruction using a modified dual-plane A to T flap.
AB  - Forehead defects often present myriad challenges for the reconstructive surgeon.
      Many options exist for forehead reconstruction, from primary closure to free
      flaps. To optimally match colour, contour and texture, the best approach replaces
      'like with like'. When primary closure is not possible due to size limitations,
      and colour or depth is not suitable for grafts, then locoregional flaps become
      the mainstay of repair. The authors present three cases in which a dual-plane
      modified A to T flap is used to reconstruct central and lateral forehead defects
      up to 8 cm in size with excellent aesthetic results. This technique applies
      principles of the periglabellar flap, with modifications designed to encompass
      larger defects as well as defects of the lateral forehead. 

PMID- 24294022
TI  - Extensor indicis proprius opponensplasty for isolated traumatic low median nerve
      palsy: A case series.
AB  - INTRODUCTION: The standard opponensplasty for isolated low median nerve palsy in
      nonleprosy patients uses the flexor digitorum superficialis of the ring finger.
      OBJECTIVE: To report the results of extensor indicis proprius (EIP)
      opponensplasty in 15 consecutive nonleprosy patients with isolated traumatic low
      median nerve palsy. METHODS: A retrospective study of the author's cases of EIP
      opponensplasty for isolated traumatic median nerve palsy over the past 15 years
      was conducted. The author used the EIP to restore thumb opposition in all cases
      of isolated median nerve palsies when the following conditions were present:
      protective sensibility in the median nerve distribution; normal power of EIP;
      supple hands; and full passive range of opposition with no contracture of the
      first web space. There were a total of 15 patients with a mean age of 30 years
      (range 20 to 45 years). They all had traumatic isolated low median nerve palsy
      with recovery of at least protective sensation and no recovery of opposition. The
      tendon was harvested just proximal to the extensor expansion, the flexor carpi
      ulnaris was used as a pulley and the insertion was to the tendon of abductor
      pollicis brevis. RESULTS: There were no postoperative complications or extension
      lag of the donor finger. Using previously published criteria, 12 patients
      experienced excellent results while the remaining three had a good result.
      CONCLUSIONS: In nonleprosy patients with isolated traumatic low median nerve
      palsy, the results of this transfer are consistent and there is no need to
      harvest the EIP tendon distal to the extensor expansion because a single
      insertion to the abductor pollicis brevis is sufficient.

PMID- 24294023
TI  - Concomitant sublay mesh repair of umbilical hernia and abdominoplasty.
AB  - Concomitant mesh repair of large umbilical hernias and abdominoplasty pose a
      serious risk of devascularizing the umbilical stalk. A technique of placing mesh
      in a sublay manner, deep to the fascial defect, for an umbilical herniorrhaphy to
      avoid damage to the deep umbilical perforators during an abdominoplasty is
      described. 

PMID- 24294024
TI  - Compensating a plastic surgeon: What is the best way to reward quality while
      optimizing efficiency?

PMID- 24294025
TI  - Oral exam.

PMID- 24294026
TI  - Factors that motivate people to undergo cosmetic surgery.
AB  - A sample of 204 British participants completed a questionnaire that assessed
      their attitude toward cosmetic surgery as well as measures of self-esteem, life
      satisfaction, self-rated physical attractiveness, religiosity and media
      consumption. Two factors emerged from a factor analysis of their attitudes toward
      surgery: likelihood to undergo, and benefits of undergoing, cosmetic surgery.
      Females with low self-esteem, low life satisfaction, low self-rated
      attractiveness and little religious beliefs who were heavy television watchers
      reported a greater likelihood of undergoing cosmetic surgery. Stepwise regression
      analysis with the two attitude factors as criterion variables showed two major
      predictors for likelihood: religiousness and low self-esteem, and four major
      predictors for benefit: religousness, media consumption, life satisfaction and
      sex. The role of religion is considered in this context. 

PMID- 24294027
TI  - In utero arterial thrombosis treated with recombinant tissue plasminogen
      activator in an infant of a diabetic mother: A case report and literature review.
AB  - A 36+5 days' gestation infant of a diabetic mother suffered arterial thrombosis
      with severe vascular occlusions in multiple limbs, especially of the left upper
      extremity. Although the mechanism remains elusive, the association between venous
      and arterial thrombi in infants and diabetic mothers has previously been
      established. Cases typically result in the amputation of the dysvascular limbs.
      In the present case, the use of selective angiography to administer recombinant
      tissue plasminogen activator allowed the left upper extremity to be salvaged with
      amputation of only the left thumb. 

PMID- 24294028
TI  - Nonprogessive size reduction of limbs involved in giant congenital nevi: A
      magnetic resonance imaging study.
AB  - Giant congenital nevi are hamartomas of neuroectodermal origin predominantly
      involving the trunk; two or more body segments are also commonly involved. A
      feature observed when giant congenital nevi are involved in a limb is a
      nonprogressive reduction in limb size. This feature has been evaluated, and
      demonstrates alterations only in the skin and subcutaneous tissue of the affected
      limb, with all other structures normal compared with the unaffected contralateral
      limb. The present magnetic resonance imaging study clearly demonstrates the
      substitution of subcutaneous tissue and fat cells by nevus cells, leading to a
      dramatic volume reduction in these tissues. The volumes of the deeper structures
      were not affected. 

PMID- 24294029
TI  - Depression increases the risk for uncontrolled hypertension.
AB  - BACKGROUND: Because hypertension and depression share common pathways, it is
      possible that each disease has an impact on the natural history of the other.
      OBJECTIVE: To determinate whether depression influences blood pressure control in
      hypertensive patients. METHODS: Forty hypertensive patients undergoing
      antihypertensive treatment, excluding beta-blockers and central-acting agents,
      self-measured their blood pressure several times a day for three days using a
      validated, commercially available device. All patients also completed the Zung
      Self-rating Depression Scale survey for depression. Associations between the
      results of the blood pressure and depression tests were determined using the
      Spearman correlation coefficient; RR was also measured. RESULTS: Of the 40
      patients, 23 were depressed, and 21 of these 23 had poor control of their blood
      pressure. The RR for uncontrolled hypertension in depressed patients was 15.5. A
      significant correlation between systolic (r=0.713) and diastolic (r=0.52) blood
      pressure values and depression was found. CONCLUSION: Depression is common in
      patients with uncontrolled hypertension and may interfere with blood pressure
      control. Screening for depression in hypertensive patients is a simple and cost
      effective tool that may improve outcomes.

PMID- 24294030
TI  - Effect of prostaglandin E1 inhalation on pulmonary hypertension following
      corrective surgery for congenital heart disease.
AB  - BACKGROUND: Intravenous infusion of prostaglandin E1 (PGE1) has been used to
      treat pulmonary arterial hypertension (PAH); however, the efficacy and safety of
      inhaled PGE1 is unclear. OBJECTIVES: To investigate the effect of inhaled PGE1 on
      PAH following corrective surgery for congenital heart disease. METHODS: Sixty
      patients with postoperative residual PAH following corrective surgery for
      congenital heart disease were randomly assigned to a control group, a PGE1
      infusion group (intravenous PGE1 infusion; 30 ng/kg/min daily for 10 days) or a
      PGE1 inhalation group (100 MUg nebulized PGE1 every 8 h for 10 days). Systolic
      blood pressure, mean pulmonary arterial pressure, arterial oxygen pressure,
      oxygen saturation and serum endothelin-1 level were measured before and after the
      treatment. RESULTS: At the end of the study, the mean pulmonary arterial pressure
      in the two PGE1 groups were lower than in the control group (P<0.01), whereas the
      mean arterial oxygen pressure was higher (P<0.01). Compared with the PGE1
      infusion group, the mean pulmonary arterial pressure in the PGE1 inhalation group
      was lower (P<0.01) whereas the arterial oxygen pressure was higher (P<0.01). The
      mean endothelin-1 levels in the two PGE1 groups were lower than in the control
      group (P<0.01), but there was no statistically significant difference in
      endothelin-1 levels between the PGE1 inhalation and infusion groups (P>0.05).
      CONCLUSIONS: In pediatric patients with PAH, PGE1 inhalation was associated with
      a reduction in pulmonary arterial pressure and improvement in arterial blood
      oxygen levels.

PMID- 24294031
TI  - Percutaneous coronary intervention delays pacemaker implantation in coronary
      artery disease patients with established bradyarrhythmias.
AB  - BACKGROUND: Pacemakers have long been used to assist the heart under pathological
      conditions, and they are the first choice in the treatment of systematic
      bradyarrhythmias. However, the effect of percutaneous coronary intervention (PCI)
      in patients with coronary artery disease as well as bradyarrhythmias remains
      unknown. METHODS: In the present study, 42 patients with chest pain and/or
      abnormal stress test results were surveyed. Before coronary angiography, patients
      underwent complete examination, including a 24 h dynamic electrocardiogram, which
      was used to diagnose bradyarrhythmias that were not suitable for pacemaker
      implantation due to a lack of arrhythmia-related symptoms. All patients underwent
      PCI but did not undergo pacemaker implantation. Forty-one patients with chest
      pain and/or abnormal stress test results, as well as symptom-free
      bradyarrhythmias, were selected as the control group. All of the patients in the
      control group were committed to treatments without PCI. RESULTS: During a mean
      (+/-SD) of 3.3+/-0.5 years of follow-up (range 2.5 to 4.5 years), 24 of 42
      patients who received PCI underwent pacemaker implantation for arrhythmia-related
      symptoms, eight were shown by Holter monitoring to have worsened but still
      exhibited no symptoms, and the remainder did not show any changes according to
      the examinations performed. In the control group, 31 patients underwent pacemaker
      implantation for arrhythmia-related symptoms, eight were shown by Holter
      monitoring to have worsened but still exhibited no symptoms, and two did not show
      any changes according to the examinations performed. Nevertheless, the rates of
      pacemaker implantation each year (from the first to the third year) between the
      two groups were 7.1% versus 39.0% (P=0.001); 33.3% versus 63.4% (P=0.006); and
      57.1% versus 75.6%, (P=0.075), respectively. CONCLUSIONS: The present study found
      that PCI delayed the demand for pacemaker implantation among coronary artery
      disease patients.

PMID- 24294032
TI  - Mitral valve repair versus replacement in simultaneous aortic and mitral valve
      surgery.
AB  - BACKGROUND: Double valve replacement for concomitant aortic and mitral valve
      disease is associated with substantial morbidity and mortality. Excellent results
      with valve repair in isolated mitral valve lesions have been reported; therefore,
      whether its potential benefits would translate into better outcomes in patients
      with combined mitral-aortic disease was investigated. METHODS: A retrospective
      observational study was performed involving 341 patients who underwent aortic
      valve replacement with either mitral valve repair (n=42) or double valve
      replacement (n=299). Data were analyzed for early mortality, late valve-related
      complications and survival. RESULTS: The early mortality rate was 11.9% for valve
      repair and 11.0% for replacement (P=0.797). Survival (+/- SD) was 67+/-11% in
      mitral valve repair with aortic valve replacement and 81+/-3% in double valve
      replacement at five years of follow-up (P=0.187). The percentage of patients who
      did not experience major adverse valve-related events at five years of follow-up
      was 83+/-9% in those who underwent mitral valve repair with aortic valve
      replacement and 89+/-2% in patients who underwent double valve replacement
      (P=0.412). Age >70 years (HR 2.4 [95% CI 1.1 to 4.9]; P=0.023) and renal
      dysfunction (HR 1.9 [95% CI 1.2 to 3.7]; P=0.01) were independent predictors of
      decreased survival. CONCLUSIONS: In patients with double valve disease, both
      mitral valve repair and replacement provided comparable early outcomes. There
      were no significant differences in valve-related reoperations, anticoagulation
      related complications or prosthetic valve endocarditis. Patient-related factors
      appear to be the major determinant of late survival, irrespective of the type of
      operation.

PMID- 24294033
TI  - Right ventricular myocardial infarction: From pathophysiology to prognosis.
AB  - Right ventricle myocardial infarctions (RVMIs) accompany inferior wall ischemia
      in up to one-half of cases. The clinical sequelae of RVMIs vary from no
      hemodynamic compromise to severe hypotension and cardiogenic shock. Diagnosis is
      based on physical examination, electrocardiography, echocardiography and coronary
      angiography. Because the standard 12-lead electrocardiogram is insufficient for
      the assessment of RV involvement, right-sided precordial leads should always be
      included. Adequate fluid administration in combination with positive inotropic
      agents and early coronary reperfusion are crucial components of treatment, while
      diuretics and nitrates should be avoided. Intra-aortic balloon counterpulsation
      and right ventricle assist devices may be used with success in RVMIs associated
      with medically refractory heart failure. Right ventricular involvement appears to
      be an independent prognostic factor that dramatically increases in-hospital
      mortality, due, in part, to a significantly higher risk of hemodynamically
      compromising arrhythmias. Thus, using right-sided precordial leads and early RVMI
      identification to trigger an appropriately aggressive treatment protocol may
      improve patients' prognosis. 

PMID- 24294034
TI  - Cardioverter-defibrillator implantation in myeloma-associated cardiac
      amyloidosis.
AB  - A 62-year-old woman with multiple myeloma and light-chain amyloidosis with
      significant heart involvement developed an in-hospital cardiac arrest. After
      cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage
      was restored, and the patient was admitted to the coronary care unit. A
      cardioverter-defibrillator was implanted, and it successfully intervened in two
      sustained ventricular tachycardia episodes and one ventricular fibrillation
      episode, which were recorded during hospitalization. After achieving discrete
      cardiac compensation, the patient was transferred to the emergency medicine
      department where she underwent chemotherapy for multiple myeloma. The patient
      died 40 days after admission from refractory heart failure. In the literature,
      there are studies that describe the use of cardioverter-defibrillator
      implantation in cardiac amyloidosis; however, at present, there is no evidence of
      a beneficial effect on survival with the use of this intervention. A high index
      of suspicion for amyloid heart disease and early diagnosis are critical to
      improving outcomes. 

PMID- 24294035
TI  - Pacemaker-mediated angina.
AB  - Angina is a clinical syndrome characterized by discomfort in the chest, jaw,
      shoulder, back or arm. It is typically aggravated by exertion or emotional stress
      and relieved by nitroglycerin. Atherosclerotic coronary artery disease is the
      most common cause of angina. Dual-chamber pacemakers track the atrial electrical
      activity by pacing the ventricle. The present article reports the first case in
      the literature involving pacemaker-mediated angina. A 78-year-old man complained
      of chest pain shortly after the placement of a permanent dual-chamber pacemaker
      and experienced immediate relief of his pain after the pacemaker mode was
      switched from tracking the atrium and pacing the ventricle to sensing and pacing
      the ventricle. The pain was identified as angina pectoris. The comprehensive
      history-taking performed before pacemaker placement helped to quickly identify
      the cause of the patient's pain. 

PMID- 24294036
TI  - Effect of the stellate ganglion on atrial fibrillation and atrial
      electrophysiological properties and its left-right asymmetry in a canine model.
AB  - OBJECTIVE: To investigate the effect of the stellate ganglion (SG) and its left
      right asymmetry on atrial fibrillation (AF) inducibility, AF duration and atrial
      electrophysiological properties. METHODS: Sixteen adult mongrel dogs were
      randomly assigned to three groups. The control group (n=4) underwent 6 h rapid
      atrial pacing (RAP) only; the right SG (RSG) group (n=6) underwent 6 h RSG
      stimulation plus RAP; and the left SG (LSG) group (n=6) underwent 6 h LSG
      stimulation plus RAP. AF induction rate, AF duration, effective refractory period
      (ERP) and dispersion of ERP (dERP) were measured. RESULTS: In the RSG group, the
      induction rate of AF was significantly increased in sites in the right atrium
      (RA) compared with baseline (P<0.05). In the LSG group, the induction rate of AF
      was significantly increased (P<0.05) compared with baseline in the left atrium
      (LA), left superior pulmonary vein and left inferior pulmonary vein,
      respectively. Compared with RSG stimulation, right stellate ganglionectomy
      markedly decreased the AF induction rate of the RA (P<0.05). Compared with LSG
      stimulation, left stellate ganglionectomy markedly decreased the AF induction
      rate of the LA, the left superior pulmonary vein and the left inferior pulmonary
      vein (P<0.05). In the RSG group, the ERP was significantly shortened (P<0.05) and
      the dERP was significantly increased (P<0.05) in RA sites (P<0.05). The ERP was
      significantly shortened in the LSG group (P<0.05). The dERP was significantly
      increased (P<0.05) in LA and pulmonary vein sites (P<0.05). CONCLUSIONS:
      Unilateral electrical stimulation of the SG in combination with RAP can
      successfully establish a canine model of acute AF mediated by excessive
      sympathetic activity. SG stimulation facilitates AF induction and aggravates
      electrical remodelling in sites in the atrium and pulmonary vein. Inhibiting
      sympathetic nerve activation through unilateral stellate ganglionectomy can
      reduce AF initiation.

PMID- 24294037
TI  - Validation of the vitronectin knockout mouse as a model for studying myocardial
      infarction: Vitronectin appears to influence left ventricular remodelling
      following myocardial infarction.
AB  - BACKGROUND: Vitronectin (VN) is an abundant acute-phase plasma protein that
      regulates cell adhesion and migration as well as interactions with components of
      the plasminogen activator/plasmin system, specifically plasminogen activator
      inhibitor type 1. This system plays a major role in tissue remodelling regulating
      wound healing after myocardial infarction. OBJECTIVES: To investigate the
      feasibility of using VN knockout mice (VN(-/-)) to study the role of VN on
      ventricular remodelling following myocardial infarction. METHODS: Specifically
      bred VN(-/-) mice and normal wild-type (VN(+/+)) mice underwent coronary artery
      ligation and were assessed 28 days postligation using echocardiography and
      morphometric histology. RESULTS: No difference was observed between VN(-/-) mice
      and VN(+/+) mice with respect to gross phenotype, weight, coronary anatomy or
      echocardiographically measured ejection fraction (56%). Following myocardial
      infarction, VN(-/-) mice exhibited less ventricular dilation and less impairment
      in echocardiographic ejection fraction compared with VN(+/+) mice (48% versus
      41%; P=0.01). VN(-/-) mice also exhibited smaller infarcts on morphometric
      analysis. CONCLUSIONS: The results of the present study confirmed the feasibility
      of using coronary artery ligation in VN knockout mice to investigate the role of
      VN in post-myocardial infarction remodelling. The absence of VN appears to result
      in favourable effects on wound healing. These data suggest that this model may
      offer novel insights into the role of VN in the regulation of myocardial
      remodelling.

PMID- 24294038
TI  - A novel measurement technique for the design of fenestrated stent grafts:
      Comparison with three-dimensional aorta models.
AB  - BACKGROUND: Stent graft placement is an acceptable treatment option for aortic
      disease, particularly for abdominal aortic aneurysm. At present, the use of stent
      grafts is expanding beyond current indications for use. Fenestrated stent grafts
      are used in patients with abdominal aortic aneurysms whose aortic anatomy is
      unsuitable for repair using standard devices. The success of fenestrated stent
      graft placement is largely dependent on planning, including obtaining
      measurements and designing the stent. OBJECTIVE: To demonstrate a measurement
      technique that may be used for the design of fenestrated stent grafts to repair
      endovascular aneurysms, and to compare these measurements, obtained using
      archived two-dimensional patient data, with measurements obtained using a three
      dimensional (3-D) computer-assisted design model. METHODS: Fenestrated stent
      grafts were designed and fabricated based on computed tomographic angiography
      images. 3-D models were constructed using modelling software and rapid
      prototyping technology incorporated with fused deposition modelling. The stent
      grafts were trunk-type, with four holes for the visceral branches (celiac axis,
      superior mesenteric artery, right renal artery and left renal artery). Computed
      tomography scans of 10 patients with abdominal aortic aneurysms were reviewed.
      Axial, multiplanar reconstruction and curved multiplanar reconstruction images
      were used to measure 11 parameters. Sizing of the fenestrated aortic stent grafts
      was performed independently by an experienced interventional radiologist, and the
      results were compared with the same measurements calculated using the 3-D aorta
      model (generated using Materialise Interactive Medical Image Control System
      software [Materialise NV, Belgium]). Data were reported as the mean of the
      measurements. Measurements were evaluated using Bland-Altman analysis and
      concordance correlation coefficients (CCCs). RESULTS: A total of 10 fenestrated
      stent grafts were fabricated. The proximal landing section above the celiac axis
      (one point of the wall being defined as the standard point) was 3 cm, and the
      distal flared section was 3 cm below the lowest renal artery. Ten computer
      assisted design aorta models were successfully constructed. Measurements of the
      aortic diameter showed high agreement between those obtained using the archived
      patient computer system stent graft and those obtained using the 3-D aorta model.
      The CCC for variability was 0.9974. The distance from the standard point to the
      branch vessels also demonstrated good agreement. The CCC for variability was
      0.9999. DISCUSSION: A direct measurement technique using a standard point was
      simple to perform and was easily applied to the fabrication process. Preparation
      time will likely be shortened and the versatility of stent grafts will be
      improved using this method. It will be possible to produce standardized
      fenestrated stent grafts once patients' measurements are recorded and analyzed.
      CONCLUSION: A fenestrated stent graft design technique using measurements of
      distance from a standard point generally showed a high level of agreement with a
      3-D aorta model.

PMID- 24294039
TI  - Role of gamma-glutamyltransferase in cardiovascular diseases.
AB  - Cardiovascular diseases are threatening human health with rising morbidity and
      mortality rates. Gamma-glutamyltransferase (GGT) has been found to be involved in
      the pathogenesis of cardiovascular diseases, especially coronary artery disease,
      and the prognosis of cardiovascular disease may be predicted by increasing GGT
      levels. GGT levels are related to cardiovascular emergencies of chronic heart
      failure, and an elevated GGT level has been shown to be an independent predictive
      maker for cardiac death and cardiac transplantation. Investigation of the role of
      GGT in the mechanism of cardiac diseases will be helpful in developing preventive
      strategies and treatment methods. 

PMID- 24294040
TI  - Left ventricular systolic and diastolic function in subjects with a bicuspid
      aortic valve without significant valvular dysfunction.
AB  - BACKGROUND: The bicuspid aortic valve (BAV) represents the most common cardiac
      congenital malformation in adults. It is frequently associated with dilation,
      aneurysm and dissection of the ascending aorta. OBJECTIVE: To evaluate left
      ventricular systolic and diastolic function in subjects with BAVs. METHODS:
      Thirty-five subjects with BAV (mean [+/- SD] age 25.9+/-5.7 years [range 17 to 36
      years]; 18 male, 17 female) with either no valvular impairment or mild valvular
      impairment were recruited along with 30 control subjects (24.5+/-4.4 years of age
      [range 15 to 35 years]; 15 male, 15 female) who were matched for age, sex and
      body surface area. Left ventricular systolic and diastolic function were
      evaluated using conventional and tissue Doppler echocardiography. Left
      ventricular systolic and diastolic parameters were compared between the two
      groups. RESULTS: In subjects with BAVs, the ratio of mitral early diastolic
      velocity to late diastolic velocity was lower (0.95+/-0.4 versus 1.27+/-0.9;
      P=0.001), the ratio of mitral early diastolic velocity to myocardial early
      diastolic velocity was higher (10.1+/-3.2 versus 6.5+/-2.4; P=0.001) and the
      myocardial early diastolic velocity was lower (8.4+/-2.1 versus 15.3+/-3.6;
      P<0.001) compared with control subjects. In addition, the myocardial performance
      index was higher in subjects with BAVs than in control subjects (P=0.03). The
      left ventricular ejection fraction was also lower (53+/-11% versus 64+/-13%;
      P<0.001). No other statistically significant differences were observed between
      the two groups with regard to left ventricular systolic and diastolic parameters.
      In addition, the number of mitral valve prolapses and atrial septal aneurysms was
      higher in subjects with BAVs. CONCLUSION: BAVs may be associated with left
      ventricular systolic and diastolic dysfunction.

PMID- 24294041
TI  - Hematological parameters and coronary collateral circulation in patients with
      stable coronary artery disease.
AB  - BACKGROUND: Although hematological parameters have been associated with prognosis
      in patients with various cardiovascular diseases, their relationship with
      coronary collateral (CC) circulation in patients with stable coronary artery
      disease (CAD) is unknown. OBJECTIVE: To investigate the relationship between
      hematological parameters and CC vessel development in patients with stable CAD.
      METHODS: A total of 96 patients who underwent coronary angiography were
      retrospectively enrolled. All study participants had at least one occluded major
      coronary artery. Development of CCs was classified using the method of Rentrop.
      Rentrop grades of 0 and 1 indicate poor CCs, whereas grades 2 and 3 indicate good
      CCs. Hematological parameters, including mean platelet volume (MPV) and
      neutrophil/lymphocyte (N/L) ratio, were measured. Multivariate logistic
      regression analysis was performed to identify independent variables. RESULTS: The
      MPV and N/L ratio were significantly higher in the poor CC group compared with
      the good CC group. Negative correlations were found in the analyses comparing
      Rentrop score with MPV and N/L ratio (r=-0.274; P=0.012 and r=-0.339; P=0.001,
      respectively). In multivariate analysis, the N/L ratio was independently related
      to CC circulation (OR 0.762 [95% CI 0.587 to 0.988]; P=0.04). CONCLUSION: The
      results suggest that N/L ratio and MPV are associated with poor CCs, and a high
      N/L ratio is a significant predictor of poor CC development in patients with
      stable CAD.

PMID- 24294042
TI  - High prevalence of subclinical thyroid dysfunction and the relationship between
      thyrotropin levels and cardiovascular risk factors in residents of the coastal
      area of China.
AB  - OBJECTIVES: To investigate the prevalence of subclinical thyroid dysfunction and
      the relationship between thyrotropin levels and cardiovascular risk factors in
      residents of the coastal area of China. METHODS: Atotalof4256individuals(mean[+/
      SD]age50.51+/-14.24years; 2079 males, 2177 females,) were enrolled in the present
      study. Sex, blood pressure, body mass index, waist-to-hip ratio, serum levels of
      fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, triglycerides, uric acid and smoking status were
      measured. The relationship between thyrotropin levels and cardiovascular risk
      factors was analyzed. RESULTS: The overall prevalence of thyroid dysfunction was
      11.07%. The prevalence of subclinical hypothyroidism (6.32%) was higher than that
      of hyperthyroidism (1.53%). The prevalence of thyroid dysfunction among female
      subjects was higher than that among male subjects (16.54% versus 5.34%,
      respectively; P<0.001). Significant differences were detected with respect to
      body mass index (P=0.026), waist-to-hip ratio (P<0.001), fasting glucose levels
      (P=0.001), total cholesterol levels (P=0.013), triglyceride levels (P=0.003) and
      smoking status according to different thyrotropin levels. CONCLUSION: The
      prevalence of thyroid dysfunction was high in residents of China's coastal area.
      Significant differences were detected with regard to body mass index, waist-to
      hip ratio, fasting glucose levels, total cholesterol levels, triglyceride levels
      and smoking status according to different thyrotropin levels.

PMID- 24294043
TI  - How do cardiorespiratory fitness improvements vary with physical training
      modality in heart failure patients? A quantitative guide.
AB  - BACKGROUND: Peak oxygen consumption (VO2) is the gold standard measure of
      cardiorespiratory fitness and a reliable predictor of survival in chronic heart
      failure patients. Furthermore, any form of physical training usually improves
      cardiorespiratory fitness, although the magnitude of improvement in peak VO2 may
      vary across different training prescriptions. OBJECTIVE: To quantify, and
      subsequently rank, the magnitude of improvement in peak VO2 for different
      physical training prescriptions using data from published meta-analyses and
      randomized controlled trials. METHODS: Prospective randomized controlled parallel
      trials and meta-analyses of exercise training in chronic heart failure patients
      that provided data on change in peak VO2 for nine a priori comparative analyses
      were examined. RESULTS: All forms of physical training were beneficial, although
      the improvement in peak VO2 varied with modality. High-intensity interval
      exercise yielded the largest increase in peak VO2, followed in descending order
      by moderate-intensity aerobic exercise, functional electrical stimulation,
      inspiratory muscle training, combined aerobic and resistance training, and
      isolated resistance training. With regard to setting, the present study was
      unable to determine whether outpatient or unsupervised home exercise provided
      greater benefits in terms of peak VO2 improvment. CONCLUSIONS: Interval exercise
      is not suitable for all patients, especially the high-intensity variety; however,
      when indicated, this form of exercise should be adopted to optimize peak VO2
      adaptations. Other forms of activity, such as functional electrical stimulation,
      may be more appropriate for patients who are not capable of high-intensity
      interval training, especially for severely deconditioned patients who are
      initially unable to exercise.

PMID- 24294044
TI  - Combined circumferential and longitudinal left ventricular systolic dysfunction
      in patients with type 2 diabetes mellitus without myocardial ischemia.
AB  - BACKGROUND/OBJECTIVE: Left ventricular (LV) circumferential or longitudinal
      shortening may be impaired in patients with type 2 diabetes mellitus (DM). In the
      present study, patients with type 2 DM without myocardial ischemia and combined
      impairment of circumferential and longitudinal (C+L) shortening were studied to
      assess the prevalence and factors associated with this condition. METHODS: Data
      from 386 patients with type 2 DM enrolled in the SHORTening of midWall and
      longitudinAl left Ventricular fibers in diabEtes study were analyzed. One hundred
      twenty healthy subjects were used to define C+L dysfunction. Stress-corrected
      midwall shortening and mitral annular peak systolic velocity were considered as
      indexes of C+L shortening and classified as low if <89% and <8.5 cm/s,
      respectively (10th percentiles of controls). RESULTS: Combined C+L dysfunction
      was detected in 66 patients (17%). The variables associated with this condition
      were lower glomerular filtration rate (OR 0.98 [95% CI 0.96 to 0.99], greater LV
      mass (OR 1.05 [95% CI 1.02 to 1.08]), high pulmonary artery wedge pressure (OR
      1.23 [95% CI 1.04 to 1.44]) and mitral annular calcifications (OR 3.35 [95% CI
      1.71 to 6.55]). Considering the entire population, the relationship between
      stress-corrected midwall shortening and peak systolic velocity was poor (r=0.20),
      and the model was linear. The relationship was considerably closer and nonlinear
      in patients with combined C+L dysfunction (r=0.61; P<0.001), having the best fit
      by cubic function. CONCLUSIONS: Combined C+L dysfunction was present in one-sixth
      of patients with type 2 DM without myocardial ischemia. This condition was
      associated with reduced renal function, worse hemodynamic status and structural
      LV abnormalities, and may be considered a preclinical risk factor for heart
      failure.

PMID- 24294045
TI  - Prevalence of mixed dyslipidemia among Australian patients undergoing lipid
      modifying therapy.
AB  - BACKGROUND: Few studies have assessed the prevalence of mixed dyslipidemia (MD)
      and the effectiveness of lipid-modifying therapy (LMT) for the treatment of
      abnormal levels of low-density lipoprotein cholesterol (LDL-C), triglycerides
      (TG) and high-density lipoprotein cholesterol (HDL-C) in Australian clinical
      practice. OBJECTIVE: To estimate the prevalence of MD in Australian patients
      undergoing LMT. METHODS: Patients 35 years of age and older undergoing LMT for
      >=1 year were enrolled from nine general practice and
      cardiologist/endocrinologist outpatient clinics in Australia between April 2007
      and May 2008. Lipid levels, including LDL-C, HDL-C and TG levels, were
      prospectively collected at the enrollment date and from patient records one year
      before LMT was initiated. Normal lipid levels were assessed according to
      Australian guidelines. Multivariate logistic regression was used to evaluate
      predictors of normal lipid level attainment. RESULTS: Of 297 patients (mean age
      60.1 years; 43% male), the prevalence of MD before LMT was 61%; 93% of patients
      had elevated LDL-C levels, 17% had low HDL-C levels and 62% had elevated TG
      levels. Following LMT (98.3% statins), 31% of patients had MD. The prevalence of
      elevated LDL-C levels, low HDL-C levels and elevated TG levels were 44%, 21% and
      42%, respectively. Baseline lipid levels were significant predictors of
      attainment of normal LDL-C levels (OR 0.42 [95% CI 0.27 to 0.63]) and TG levels
      (OR 0.26 [95% CI 0.16 to 0.45]). CONCLUSION: Among Australian patients primarily
      treated with statins, nearly one-third had MD despite LMT. LMT considerably
      improved LDL-C goal attainment; however, a large proportion of patients did not
      achieve normal HDL-C and TG levels. Patients may benefit from a more
      comprehensive approach to lipid management that treats all three lipid risk
      factors, as suggested in clinical guidelines.

PMID- 24294046
TI  - Relationship between serum uric acid levels and ventricular function in patients
      with idiopathic pulmonary hypertension.
AB  - OBJECTIVE: To investigate the relationship between serum uric acid levels and
      pulmonary hypertension in patients with idiopathic pulmonary artery hypertension
      (IPAH). METHODS: Serum uric acid levels were measured in 86 patients (mean [+/-
      SD] age 35.2+/-12.3 years; 36 men) with IPAH. Pulmonary arterial pressure and
      ventricular function were assessed using echocardiography. Serum uric acid levels
      were also measured in 40 healthy subjects (35.9+/-11.6 years of age; 15 men).
      RESULTS: Serum uric acid levels in IPAH patients were higher compared with
      control subjects (405+/-130 MUmol/L versus 344+/-96 MUmol/L; P<0.05). Fifty-two
      (60.4%) of the 86 patients with IPAH had elevated serum uric acid levels. The
      pulmonary systolic pressure and mean pulmonary pressure in the high uric acid
      group were higher than in the normal uric acid group (P<0.05). The left and right
      ventricular ejection fractions were lower in the high uric acid group compared
      with the normal uric acid group (P<0.05). Serum uric acid levels were correlated
      with the mean pulmonary arterial pressure (r=0.387; P<0.01) and New York Heart
      Association class (r=0.41; P<0.01). There was also an inverse correlation between
      uric acid levels and the left (r=-0.550; P<0.01) and right ventricular ejection
      fractions (r=-0.481; P<0.05). CONCLUSION: Serum uric acid levels are associated
      with IPAH severity and the severity of ventricular dysfunction.

PMID- 24294047
TI  - Atorvastatin improves endothelial progenitor cell function and reduces pulmonary
      hypertension in patients with chronic pulmonary heart disease.
AB  - OBJECTIVE: To explore the effects of atorvastatin on the migration and adhesion
      of endothelial progenitor cells (EPCs) and on pulmonary artery pressure (PAP) in
      patients with chronic pulmonary heart disease. METHODS: A total of 68 patients
      with chronic pulmonary heart disease were randomly assigned to either a control
      group (n=35) or a treatment group (n=33). In addition, 30 healthy volunteers (17
      male, 13 female) were enrolled as healthy controls. Atorvastatin (20 mg per day)
      was administered to the treatment group. The migration and adhesion activities of
      EPCs in peripheral blood were assessed before and six months after the treatment.
      PAP was measured using echocardiography before and after the treatment. RESULTS:
      EPC number, migration ability and adhesion activity in the peripheral blood of
      patients in the control and treatment groups were lower than in patients in the
      healthy control group at baseline (all P<0.05). After six months of atorvastatin
      therapy, the number of EPCs in the treatment group was greater than in the
      control group (P<0.05). Migration and adhesion functions of EPCs in the treatment
      group were greater than in the control group (all P<0.05). The reduction in PAP
      in the treatment group was greater than in the untreated control group following
      six months of therapy (P<0.05). CONCLUSION: Atorvastatin therapy increased the
      migration and adhesion activities of EPCs in patients with chronic pulmonary
      heart disease. Atorvastatin treatment was also associated with a reduction in PAP
      in these patients.

PMID- 24294048
TI  - Abnormal myocardial perfusion and risk of heart failure in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Diabetes is a major risk factor for heart failure (HF), although the
      pathophysiological processes have not been clarified. OBJECTIVE: To determine the
      prevalence of HF and of abnormal myocardial perfusion in diabetic patients
      evaluated using technetium (99m) sestamibi single-photon emission computed
      tomography. METHODS: An observational cross-sectional study was conducted that
      included patients with type 2 diabetes mellitus who underwent echocardiography to
      diagnose HF and a pharmacological stress test with intravenous dipyridamole to
      examine cardiac scintigraphic perfusion abnormalities. Clinical and biochemical
      data were also collected. RESULTS: Of the 160 diabetic patients included, 92
      (57.6%) were in HF and 68 (42.5%) were not. When patients were stratified
      according to the presence of abnormal myocardial perfusion, those with abnormal
      perfusion had a higher prevalence of HF (93%) than those with normal perfusion
      (44.4%) (P<0.0001). Patients with HF weighed more (P=0.03), used insulin less
      frequently (P=0.01), had lower total cholesterol (P=0.05) and high-density
      lipoprotein cholesterol concentrations (P=0.002), and a greater number of their
      myocardial segments showed abnormal perfusion (P<=0.001). More HF patients had a
      history of myocardial infarction (P<0.001) compared with those without HF. In a
      logistic regression analysis, the number of segments exhibiting abnormal
      myocardial perfusion was an independent risk factor for HF. CONCLUSIONS: The
      prevalence of HF in diabetic patients was high and HF predominantly occured in
      association with myocardial ischemia.

PMID- 24294049
TI  - Evaluation of left ventricular function, rotation, twist and untwist in patients
      with hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a disease with an autosomal-dominant pattern
      of inheritance associated with a variety of disease courses, age of onset,
      symptom severity, left ventricular outflow obstruction and risk for sudden
      cardiac death. Left ventricular systolic function is typically normal in most HCM
      patients using conventional echocardiographic indexes; however, myocardial
      systolic and diastolic function are reduced, and the mechanism of myocardial
      dysfunction remains unclear. Echocardiography is an invaluable tool for the
      diagnosis and assessment of hemodynamic condition, evaluation of therapy and
      outcome, and follow-up of patients with HCM. The recent advent of speckle
      tracking imaging provides a novel index for the noninvasive assessment of left
      ventricular myocardial dysfunction, and has been confirmed by many studies. A
      search for original articles focusing on HCM and its associated twist and untwist
      mechanisms was performed in the MEDLINE and PubMed databases with no date
      restrictions. All articles identified were English-language, full-text
      publications. The reference lists of identified articles were also searched for
      additional articles and reviews. 

PMID- 24294050
TI  - Mitral annulus calcification is independently associated with all-cause
      mortality.
AB  - BACKGROUND: Mitral annulus calcification (MAC) is an important echocardiographic
      finding that is significantly associated with valvular abnormalities. However,
      the effect of documented MAC on all-cause mortality is not known. Using a large
      database, associations between MAC and long-term all-cause mortality were
      evaluated. METHODS: A retrospective analysis of 3169 echocardiograms, which were
      performed for clinical reasons in southern California between 1983 and 1998 in
      patients between 16 and 99 years of age, was performed. Mortality data were
      extracted from the national mortality database at the end of 2007. Using uni- and
      multivariate analysis, associations between total mortality and the
      echocardiographic presence of MAC documented in the final report by the
      interpreting cardiologist were evaluated. RESULTS: MAC was significantly
      associated with all-cause mortality (174 of 334 [52.1%] patients with MAC died
      versus 709 of 2835 [25.0%] patients without MAC; OR 3.26 [95% CI 2.58 to 4.10];
      P<0.001). Using multivariate analysis adjusting for age, left ventricular
      hypertrophy, sex, abnormal left ventricular systolic function and significant
      valvular abnormalities, MAC remained independently associated with all-cause
      mortality (OR 2.50 [95% CI 1.81 to 3.45]; P<0.001). CONCLUSION: Using a large
      echocardiographic database, MAC was found to be independently associated with all
      cause mortality. This finding confirms the importance of an abnormal mitral
      annulus as an important prognostic marker.

PMID- 24294051
TI  - Patent ductus arteriosus closure using an Amplatzer(TM) ventricular septal defect
      closure device.
AB  - The ductus arteriosus originates from the persistence of the distal portion of
      the left sixth aortic arch. It connects the descending aorta (immediately distal
      to the left subclavian artery) to the roof of the main pulmonary artery, near the
      origin of the left pulmonary artery. Persistence of the duct beyond 48 h after
      birth is abnormal and results in patent ductus arteriosus (PDA). PDA is rare in
      adults because it is usually discovered and treated in childhood. Mechanical
      closure remains the definitive therapy because the patency of ductus arteriosus
      may lead to multiple complications, depending on the size and flow through the
      ductus. PDA closure is indicated in patients with symptoms and evidence of left
      heart enlargement, and in patients with elevated pulmonary pressures when
      reversal is possible. Transcatheter closure is the preferred technique in adults
      because it avoids sternotomy, reduces the length of hospital stay and is
      associated with fewer complications compared with surgery. First demonstrated in
      1967, both the technique and the occluder devices used have since evolved.
      However, designing an ideal PDA occluder has been a challenge due to the
      variability in size, shape and orientation of PDAs. The present article describes
      a case involving a 35-year-old woman who presented to the Center for Advanced
      Heart Failure (Houston, USA) with congestive heart failure due to a large PDA,
      which was successfully occluded using an Amplatzer (St Jude Medical, USA)
      muscular ventricular septal defect closure device. The wider waist and dual
      retention discs of these ventricular septal defect closure devices may be
      important factors to consider in the future development of devices for the
      occlusion of large PDAs. 

PMID- 24294052
TI  - What lies beneath: Posterior ST elevation myocardial infarction with underlying
      right ventricular-paced rhythm.
AB  - A 66-year-old man with a history of coronary artery disease, stage V chronic
      kidney disease, peripheral arterial disease and a dual-chamber pacemaker
      experienced persistent chest and shoulder discomfort following his daily
      hemodialysis treatment. Treatment with clopidogrel had been discontinued three
      days previously due to impending vascular surgery. Electrocardiography revealed a
      right ventricular-paced rhythm with ST abnormalities indicative of posterior ST
      elevation myocardial infarction. The patient underwent urgent cardiac
      catheterization and required percutaneous coronary intervention for an acutely
      occluded coronary artery. The present case report emphasizes the importance of
      careful and timely review of the electrocardiogram of any patient with a
      ventricular-paced rhythm who experiences signs and symptoms consistent with acute
      coronary syndrome. Certain characteristic electrocardiographic abnormalities have
      been demonstrated to predict acute myocardial infarction in such patients. 

PMID- 24294053
TI  - Cocaine-induced coronary stent thrombosis.
AB  - Cocaine is the most commonly abused drug in patients presenting to emergency
      rooms. Compliance with medical instructions and medications is poor in patients
      who use cocaine. A case involving a 41-year-old cocaine user who developed
      subacute stent thrombosis is described. The patient underwent bare metal stent
      implantation three days before presentation and had confirmed compliance with
      dual antiplatelet therapy. The stent thrombosis was treated with a manual and
      mechanical thrombectomy, in addition to percutaneous transluminal coronary
      angioplasty. Given the issue of compliance and the increased evidence of cocaine
      induced thrombosis in native vessels and stents, it is recommended that balloon
      angioplasty alone should be the treatment of choice when intervention is
      required. 

PMID- 24294054
TI  - Omega-3 polyunsaturated fatty acid-enriched diet differentially protects two
      subpopulations of myocardial mitochondria against Ca(2+)-induced injury.
AB  - Omega-3 polyunsaturated fatty acids (PUFA) confer protection against myocardial
      injury after ischemia-reperfusion. There are two subfractions of mitochondria
      located in different regions of the cell: subsarcolemmal mitochondria (SSM) and
      interfibrillar mitochondria (IFM). The present study explored possible
      differences between Ca(2+)-induced mitochondrial swelling in rat SSM and IFM
      fractions under control conditions (control group [CG]) and after dietary
      supplementation with omega-3 PUFA (experimental group [EG]). Changes in
      mitochondrial matrix volumes were measured using the light-scattering technique.
      In the CG, the time courses of swelling were comparable in both mitochondrial
      fractions, with no difference in Ca(2+)-induced swelling between the two
      mitochondrial fractions. In the SSM fraction, no difference in the time course of
      swelling in Ca(2+)-free solution between CG and EG was detected. In the EG, both
      SSM and IFM fractions demonstrated a decreased sensitivity to Ca(2+); IFM
      fractions, however, exhibited significantly less pronounced swelling following
      Ca(2+) addition. The authors conclude that IFM and SSM fractions do not differ in
      their sensitivity to Ca(2+)-induced swelling. While dietary omega-3 PUFA
      protected both mitochondrial fractions against Ca(2+)-evoked swelling, the
      protective effect appeared to be more pronounced for the IFM fraction than for
      the SSM fraction. 

PMID- 24294055
TI  - Smooth muscle-like cells resident in the media participate in spasm-induced
      coronary intimal hyperplasia.
AB  - BACKGROUND: Coronary intimal hyperplasia occurs at the site of spasm in patients
      with vasospastic angina. The migration of vascular smooth muscle cells (VSMCs)
      from the media has been proposed as a potential mechanism; however, this has not
      been confirmed with supportive evidence. OBJECTIVE: To determine which cell types
      participate in spasm-induced coronary intimal hyperplasia. METHODS: Morphological
      changes in spastic coronary artery segments in beagles were examined using
      electron microscopy and immunohistochemical staining of cell markers at 1 h, 3 h
      and 6 h, and two and four weeks after spasm provocation. RESULTS: Small smooth
      muscle-like cells (SMLCs) were observed in the media of nonspastic coronary
      segments using electron microscopy. These cells attached side-to-side to large,
      known VSMCs. At 1 h to 6 h after spasm provocation, SMLCs separated from VSMCs,
      changed to an amoebic configuration and migrated through cleaved junctions or
      disrupted portions of the internal elastic lamina into the subendothelial space.
      The SMLCs expressed alpha-smooth muscle actin and N-cadherin, but not smooth
      muscle myosin heavy chain-1 and beta-actin, suggesting that they were
      myofibroblasts and not a synthetic phenotype of VSMCs. Intimal hyperplasia was
      observed in all preparations at two and four weeks after spasm provocation.
      Furthermore, alpha-smooth muscle actin-positive SMLCs, often amoebic in
      configuration, were observed in the hyperplastic intima. CONCLUSIONS: On coronary
      spasm provocation, SMLCs (ie, possible myofibroblasts) resident in the media
      migrate as a spearhead into the intima and play a role in coronary intimal
      hyperplasia.

PMID- 24294056
TI  - Detection of left ventricular asynchrony and its relationship with the Tei index
      in patients with coronary artery ectasia.
AB  - OBJECTIVE: To evaluate left ventricular (LV) systolic asynchrony and its
      relationship with the Tei index using tissue Doppler imaging (TDI); and to
      evaluate the relationship of thrombolysis in myocardial infarction frame count
      (TFC) and Tei index with LV asynchrony in patients with coronary artery ectasia
      (CAE). METHODS: A total of 50 CAE patients and 40 control subjects were
      evaluated. Diagnosis of CAE was made angiographically and TFC was calculated. LV
      systolic and diastolic function was assessed by conventional echocardiography and
      TDI. Evaluation of intra-LV systolic asynchrony was performed using tissue
      synchronization imaging (TSI). RESULTS: In patients with CAE, the Tei index was
      significantly higher than in controls (0.63+/-0.12 versus 0.52+/-0.12; P<0.001).
      LV systolic asynchrony parameters of TSI including SD of the peak tissue velocity
      (Ts) of the 12 LV segments (Ts-SD-12), maximal difference in Ts between any two
      of the 12 LV segments (Ts-12), SD of the Ts of the six basal LV segments (Ts-SD
      6), maximal difference in Ts between any of the six basal LV segments (Ts-6) were
      significantly lengthened in patients with subclinical hypothyroidism compared
      with controls (P<0.001, P<0.001, P<0.001 and P<0.001, respectively). In addition,
      a positive correlation was found between Ts-SD-12 and the Tei index in patients
      with CAE (r=0.841; P<0.001) and mean TFC was positively correlated with Ts-SD-12
      and the Tei index (r=0.345; P=0.013 and r=0.291; P=0.021, respectively).
      CONCLUSION: Patients with CAE exhibit evidence of LV systolic asynchrony
      according to TSI. LV systolic asynchrony is related to the Tei index and mean
      TFC. Furthermore, the Tei index is an independent risk factor for LV systolic
      asynchrony.

PMID- 24294057
TI  - The promise of the early years: How long should children wait?

PMID- 24294058
TI  - Improving the odds for effective developmental surveillance.

PMID- 24294059
TI  - A holiday wish list for Canada's Early Years System.
AB  - The evidence is clear that early childhood interventions and supports have long
      term health and social benefits - coordinated action is required to ensure that
      every Canadian child benefits. While many advances have been made to improve the
      chances for Canadian children to have a healthy opportunity for early childhood
      development, there is much to be done to ensure that they have the best
      opportunities possible. To ensure every child is able to reach their full
      potential, the following wishes are identified for Canadian children: a fairer
      share of the GDP for Canadian children; the development of a strong early years
      system; designation of a national lead on behalf of children and youth; a focus
      on prevention; and development of systems to monitor success and failure. 

PMID- 24294060
TI  - Pediatric Emergency Medicine Fellows Education Day: Addressing CanMEDS objectives
      at a national subspecialty conference.
AB  - Canadian subspecialty residency training programs are developed around the
      learning objectives listed in the seven Canadian Medical Education Directives for
      Specialists (CanMEDS) criteria. Delivering content on objectives outside of those
      traditionally acquired in clinical rotations can be a challenge. In the present
      article, the planning process, curriculum development, and evaluation and
      assessment of a national subspecialty conference model in providing CanMEDS
      objective-based content sessions in the categories other than Medical Expert
      (Professional, Scholar, Communicator, Collaborator, Manager and Health Advocate)
      is described. It is hypothesized that the development of a CanMEDS objective
      based curriculum would be positively received by subspecialty residents attending
      this conference. Attendees of sessions in a two-year curriculum cycle assessed
      the content as valuable, relevant and effective. The application of this process
      can be useful to other subspecialty residency training programs to meet the needs
      of their CanMEDS objective-based training requirements. 

PMID- 24294061
TI  - Investigation of test characteristics of two screening tools in comparison with a
      gold standard assessment to detect developmental delay at 36 months: A pilot
      study.
AB  - BACKGROUND: The ability of the Rourke Baby Record (Rourke) and the Nipissing
      District Developmental Screen (NDDS) to detect developmental delay is not known.
      OBJECTIVE: To determine the test characteristics of the Rourke and NDDS compared
      with the Bayley Scales of Infant and Toddler Development III for detecting
      developmental delay in high-risk children. METHODS: Three-year-olds were
      recruited from the IWK Health Centre (Halifax, Nova Scotia). Two cut-points were
      evaluated (one and two or more areas of concern) from the Rourke and NDDS, and
      were compared with a score of <=85 on the Bayley Scales of Infant and Toddler
      Development III. RESULTS: The majority (67.7%) of the 31 participants reported no
      concern. At one area of concern, sensitivity was 75% for both the Rourke and
      NDDS. When two areas of concern were noted, specificity was 93% for the Rourke
      and 96% for NDDS. CONCLUSIONS: Both the Rourke and the NDDS appear to be
      reasonably sensitive and specific, but further investigation is warranted.

PMID- 24294062
TI  - Cystic fibrosis adolescent transition care in Canada: A snapshot of current
      practice.
AB  - Cystic fibrosis (CF) adolescent transition is not a new health care issue, yet
      progress in many areas associated with the transition process has been slow. In
      Canada, the status of CF transition has not been previously reported. The aim of
      the present study was to describe the transition from paediatric to adult health
      care for CF patients in Canada, specifically: availability of adult CF clinic
      services; average age of transfer from paediatric to adult CF health care; and
      existing CF transition practices. Results show that access to appropriate adult
      CF health care in Canada is universal; however, the availability, quantity and
      quality of CF transition care vary among CF clinics. Over a four-year period, the
      number of CF clinics using formal transition protocols almost doubled, but more
      work remains to be performed. 

PMID- 24294063
TI  - The CanMEDS role of Collaborator: How is it taught and assessed according to
      faculty and residents?
AB  - OBJECTIVE: To explore the perspectives of paediatric residents and faculty
      regarding how the Collaborator role is taught and assessed. METHODS: Using a
      constructivist grounded theory approach, focus groups at four Canadian
      universities were conducted. Data were analyzed iteratively for emergent themes.
      RESULTS: Residents reported learning about collaboration through faculty role
      modelling but did not perceive that it was part of the formal curriculum. Faculty
      reported that they were not trained in how to effectively model this role. Both
      groups reported a need for training in conflict management, particularly as it
      applies to intraprofessional (physician-to-physician) relationships. Finally, the
      participants asserted that current methods to assess residents on their
      performance as collaborators are suboptimal. CONCLUSIONS: The Collaborator role
      should be a formal part of the residency curriculum. Residents need to be better
      educated with regard to managing conflict and handling intraprofessional
      relationships. Finally, innovative methods of assessing residents on this non
      medical expert role need to be created.

PMID- 24294064
TI  - Evidence-based milestone ages as a framework for developmental surveillance.
AB  - Developmental surveillance is the process of monitoring child development over
      time to promote healthy development and to identify possible problems.
      Standardized developmental screeners have greater sensitivity than milestone
      based history taking. Unfortunately, Canadian screening guidelines, to date, are
      sparse, logistical barriers to implementation have slowed uptake of screening
      tests and physicians continue to rely on milestones. When using clinical
      impression as a framework for surveillance, clinicians may not know when to
      consider a milestone delayed because developmental attainments exist within an
      age range and there is an absence of referenced percentiles on available
      published tables, which are particularly problematic for the cognitive and social
      emotional sectors, which are less familiar to physicians. A novel, five-sector
      milestone framework with upper limits, referenced to the best available level of
      evidence, is presented. This framework may be used in teaching and may help
      physicians to better recognize failed milestones to facilitate early
      identification of children at risk for developmental disorders. 

PMID- 24294065
TI  - Case 1: A boy with asthma and leg pain.

PMID- 24294066
TI  - Case 2: Gait disturbance with unilateral intoeing.

PMID- 24294067
TI  - Identifying depression in childhood: Symptoms, signs and significance.

PMID- 24294068
TI  - Postnatal corticosteroids to treat or prevent chronic lung disease in preterm
      infants.
AB  - Postnatal corticosteroids have been used for prevention and treatment of neonatal
      chronic lung disease (CLD) (also know as bronchopulmonary dysplasia), a
      significant cause of mortality and morbidity in preterm infants. As both
      dexamethasone and hydrocortisone administration within the first seven days of
      life is associated with an increased risk of cerebral palsy, early postnatal
      corticosteroid therapy is not recommended to prevent CLD. After seven days of
      life, dexamethasone has been shown to decrease the rate of CLD at 36 weeks'
      postmenstrual age with less impact on neurodevelopmental outcome. No trials have
      examined whether the benefits of corticosteroids outweigh the adverse effects for
      infants at high risk of, or with, severe CLD. While routine dexamethasone therapy
      of all ventilated infants is not recommended, clinicians may consider a short
      course of low-dose dexamethasone for individual infants at high risk of or with
      severe CLD. There is no evidence that hydrocortisone is an effective or safe
      alternative to dexamethasone and little evidence to support routine use of
      inhaled corticosteroids for prevention or treatment. Inhaled corticosteroids may
      be considered as an alternative to dexamethasone for treating individual infants
      with severe CLD. This revision replaces a statement published jointly with the
      American Academy of Pediatrics in 2002. 

PMID- 24294069
TI  - Using probiotics in the paediatric population.
AB  - As more is learned about the importance of the intestinal microbiome to human
      health there is increasing interest in the potential benefits of probiotics.
      Probiotics are live micro-organisms which, when consumed in adequate amounts,
      confer a health effect on the host by altering its microflora. Probiotics have
      been administered both prophylactically and therapeutically for various
      conditions. This statement defines the development and role of intestinal
      microflora, and examines the evidence supporting the use of different probiotics
      to treat common paediatric conditions, such as diarrhea, atopy, functional
      intestinal disorders and necrotizing enterocolitis. 

PMID- 24294070
TI  - Transfusion and risk of infection in Canada: Update 2012.
AB  - Although multiple critical steps are taken to minimize the risk of infection from
      transfusion of blood or blood products in developed countries, this risk can
      never be entirely eliminated. In Canada, the risks of noninfectious transfusion
      reactions, such as transfusion-related acute lung injury and major allergic or
      anaphylactic reactions, are greater than that of infection. This updated practice
      point provides an overview of transfusion infection risks in Canada. Infectious
      agents, systemic conditions, donor and recipient factors, and collection and
      infusion techniques are considered. Suggestions are offered to improve both
      system and process, and to help practitioners who are discussing informed consent
      with patients and parents before administering blood or a blood product. 

PMID- 24294071
TI  - Six new deep-water sternaspid species (Annelida, Sternaspidae) from the Pacific
      Ocean.
AB  - Most sternaspid species have been described from shallow water, and Caulleryaspis
      Sendall & Salazar-Vallejo, 2013 includes one deep water species: C. gudmundssoni
      Sendall & Salazar-Vallejo, 2013 from Iceland. In Sternaspis Otto, 1821, the most
      speciose genus, most species were described from shallow water and only three
      thrive in deep water: S. maior Chamberlin, 1919 from the Gulf of California, S.
      princeps Selenka, 1885 from New Zealand, and S. riestchi Caullery, 1944 from
      Indonesia. The study of some deep sea sternaspids from the Pacific Ocean in the
      collections of six research institutions resulted in the discovery of six
      undescribed species, and for three of them there were abundant materials showing
      ventro-caudal shield development. Caulleryaspis fauchaldi sp. n. is described
      based on specimens from Oregon and California; it differs from the known species
      because it has a shield with rounded anterior margins and its peg chaetae form
      thin, small spines. Caulleryaspis nuda sp. n. was collected off Oregon; it is
      unique because its shield lacks a layer of sediment particles firmly attached,
      but has instead a thin layer of small particles loosely attached. Four other
      species are newly described in Sternaspis: S. annenkovae sp. n. was collected
      east off the northern Kurile Islands in about 4,000 m depth; it differs from
      other species by having a bicolored body, with the introvert darker than the
      abdomen, and its ventro-caudal shield plates are divergent resulting in a divided
      fan. The second species, S. maureri sp. n. was found off Peru in 1296-6489 m
      water depths and in the Southwestern Pacific in 795-3830 m; it resembles S.
      williamsae sp. n. but differs because its shield has better-developed ribs, the
      fan has a shallow or indistinct median notch and has lateral notches well
      developed. The third species, S. uschakovi sp. n., was found in the Okhotsk Sea
      in 592-1366 m, off California in 1585 m, Gulf of California in 1200-1274 m, and
      Western Mexico in 2548 m; it resembles S. africana Augener, 1918 and S.
      andamanensis Sendall & Salazar-Vallejo, 2013 in having shields with a denticulate
      posterior margin; the latter two species live in shallow water and they differ
      from each other and from the new species by a combination of shield and papillae
      features. The fourth species, S. williamsae sp. n., was found off Oregon in 1000
      2400 m, and off California in 878-1246 m; it resembles S. annenkovae because both
      species have shields with fans narrower than the anterior margin width, but
      differ in the relative development of shield features and in the relative size of
      prostomium and mouth; as stated above it also resembles S. maureri sp. n. but its
      shield has poorly-developed ribs, its median notch is distinct, and the lateral
      notches are poorly developed or indistinct. Keys to identify all species of
      Caulleryaspis and Sternaspis are also included. 

PMID- 24294072
TI  - A new species of Euscorpius Thorell, 1876 (Scorpiones, Euscorpiidae) from south
      western Turkey.
AB  - A new scorpion species, Euscorpius lycius sp. n., is described based on specimens
      collected from Mugla and Antalya Provinces, in southwestern Turkey. It is
      characterized by a standard trichobothrial pattern (Pv=8/9, et=6, em=4, eb=4),
      small size and light brown/reddish coloration. With the description of Euscorpius
      lycius sp. n., the number of valid species of the genus Euscorpius in Turkey
      increases to 5. 

PMID- 24294073
TI  - The genus Aspidimerus Mulsant, 1850 (Coleoptera, Coccinellidae) from China, with
      descriptions of two new species.
AB  - Chinese members of the genus Aspidimerus Mulsant, 1850 are reviewed. Ten species
      are recognized, including two new species: A. zhenkangicus Huo & Ren, sp. n. and
      A. menglensis Huo & Ren, sp. n. A. kabakovi Hoang is recorded from China for the
      first time. A. blandus (Mader, 1954) is recognized as synonymous with A. ruficrus
      Gorham, 1895 (syn. n.). Aspidimerus rectangulatus Kuznetsov & Pang, 1991 and A.
      serratus Kuznetsov & Pang, 1991 are transferred to the genus Pseudaspidimerus
      Kapur, 1948 (comb. n.). All species from China are described and illustrated.
      Distribution maps of the Chinese species, a key and a catalogue of all known
      Aspidimerus are provided. 

PMID- 24294074
TI  - Three new species of the genus Probles Forster (Hymenoptera, Ichneumonidae,
      Tersilochinae) from South Korea.
AB  - Three closely related species of the genus Probles Forster, P. fulgida sp. n., P.
      korusa sp. n. and P. rukora sp. n., belong to the subgenus Euporizon Horstmann
      and differ from other Palearctic species of the genus by a combination of long
      and apically weakly sinuate ovipositor and short temple. These three species are
      assigned to a newly designated fulgida species-group, and a portion of the key
      for identification of this species-group is provided. Based on the shape of the
      ovipositor apex, the fulgida species-group resemble members of the subgenus
      Microdiaparsis Horstmann but are distinct in having a much shorter temple. 

PMID- 24294075
TI  - Discovery of the male of Lobrathium rotundiceps (Koch), and a new species of
      Lobrathium from Jiangxi, East China (Coleoptera, Staphylinidae, Paederinae).
AB  - The male of Lobrathium rotundiceps (Koch, 1939) from Zhejiang and L. luoxiaoense
      sp. n. from Jiangxi are described and illustrated. 

PMID- 24294076
TI  - Occurrence of species of the genus Pityophthorus Eichhoff (Coleoptera,
      Curculionidae, Scolytinae) in the province of Quebec, Canada.
AB  - Twig beetles in the genus Pityophthorus Eichhoff, 1864 include more than 300
      species worldwide, with maximum diversity in tropical and subtropical regions. To
      date, approximately 50 species of Pityophthorus have been recorded in Canada, and
      these species are associated mainly with coniferous trees. Since 1981, no
      comprehensive study on this difficult taxonomic group has been conducted in
      Quebec, Canada, most likely due to their limited significance as forest pests.
      Based on data gathered from five years of field sampling in conifer seed orchards
      and compiled from various entomological collections, the distribution of
      Pityophthorus species in Quebec is presented. Approximately 291 new localities
      were recorded for the Pityophthorus species. Five species-group taxa, namely
      Pityophthorus puberulus (LeConte, 1868), Pityophthorus pulchellus pulchellus
      Eichhoff, 1869, Pityophthorus pulicarius (Zimmermann, 1868), Pityophthorus
      nitidus Swaine, 1917,and Pityophthorus cariniceps LeConte&Horn, 1876 were the
      most widespread. In contrast, Pityophthorus consimilis LeConte, 1878,
      Pityophthorus intextus Swaine, 1917, Pityophthorus dentifrons Blackman, 1922,
      Pityophthorus ramiperda Swaine, 1917, and Pityophthorus concavus Blackman, 1928
      display a notably limited distribution. In addition, the first distribution
      records of Pityophthorus intextus and Pityophthorus biovalis Blackman, 1922 are
      furnished, and the subspecies Pityophthorus murrayanae murrayanae Blackman,
      1922is reported from Quebec for the second time. Moreover, distribution maps are
      provided for all Pityophthorus species recorded in the province of Quebec. 

PMID- 24294077
TI  - A new species of Ocydromia Meigen from China, with a key to species from the
      Palaearctic and Oriental Regions (Diptera, Empidoidea, Ocydromiinae).
AB  - Previously only one species of the genus Ocydromia Meigen was recorded from
      China. Here a second species of the genus from China, Ocydromia shanxiensis sp.
      n., is reported. A key to the species of the genus from the Palaearctic and
      Oriental regions is presented. 

PMID- 24294078
TI  - New species and host records of New World, mostly Neotropical, opiine Braconidae
      (Hymenoptera) reared from flower-infesting, stem-galling, and stem-mining
      Tephritidae (Diptera).
AB  - New host records (all members of the family Tephritidae) are presented for 14
      newly described species of opiine Braconidae from the neotropics and two
      previously described species, one from the neotropics and one from the Nearctic
      Region. Doryctobracon anneae Wharton, Opius baderae Wharton, O. baeblus Wharton,
      O. cablus Wharton, O. dablus Wharton, O. danielsae Wharton, O. gabriellae
      Wharton, O. godfrayi Wharton, O. marshi Wharton, O. nablus Wharton, O. pipitae
      Wharton, O. stecki Wharton, O. taramegillae Wharton, and O. yoderi Wharton are
      newly described. Hosts are newly recorded for the previously described species
      Opius nympha Fischer and O. peleus Fischer. A key is presented to Opiinae that
      have been reared from flower, stem, and leaf feeding tephritids in the New World.
      Host and host plant associations are discussed; a few of the tephritid host plant
      records are also new. Opius cosa (Fischer), is a comb. n. 

PMID- 24294079
TI  - A new species of Austrodecus Hodgson, 1907 (Arthropoda, Pycnogonida,
      Austrodecidae) from the Southwest Indian Ridge.
AB  - A new species of pycnogonid collected by the Chinese research vessel R/V
      Dayangyihao during cruises to the Southwest Indian Ridge in 2008 and 2009 is
      recorded. The new species, Austrodecus bamberi, is placed into the tristanense
      section by the characters of 4-articled ovigers and present auxiliary claws and
      is distinguished from other species in this section by the number and length of
      tubercles on the first coxae. 

PMID- 24294080
TI  - Definition and review of the lancangjiang species group of the termitophilous
      genus Orthogonius Macleay, 1825 (Coleoptera, Carabidae, Orthogoniini).
AB  - The lancanjiang species group of the termitophilous ground beetle genus
      Orthogonius Macleay, 1825, is defined and reviewed. This group is characterized
      by the black and rather elongate body, dense punctation on head and elytra, long
      and slender appendages, thin fore tibiae, and elytral interval 3 without a
      subapical setiferous pore. To date, the lancanjiang species group is composed of
      four species and one subspecies, including three new species and one new
      subspecies which are described in the present paper: O. macrophthalmus sp. n.
      (northern Vietnam), O. euthyphallus sp. n. (southern Vietnam), O. euthyphallus
      bolavenensis ssp. n. (southern Laos) and O. carinatus sp. n. (northern Laos). A
      distribution map and a key to all species of this group are also provided. 

PMID- 24294081
TI  - The hydrobioid freshwater gastropods (Caenogastropoda, Truncatelloidea) of
      Greece: new records, taxonomic re-assessments using DNA sequence data and an
      update of the IUCN Red List Categories.
AB  - Hydrobioid freshwater gastropods were collected from mainland and insular Greece.
      Several threatened taxa, such as Graecoanatolica vegorriticola, Pseudamnicola
      negropontina, Pseudamnicola pieperi, Pseudobithynia eubooensis and Pseudoislamia
      balcanica, were recorded from new localities. Trichonia trichonica, which has
      been considered extinct from its type locality for the last twenty eight years,
      was re-discovered, whereas the presence of Daphniola exigua, G. vegorriticola,
      Marstoniopsis graeca, P. pieperi and Pseudobithynia trichonis in their type
      localities was verified. The taxonomic status of P. negropontina and the newly
      discovered populations of G. vegorriticola was elucidated using COI sequence
      data. The new data recorded during this survey indicate that the IUCN status of
      some Greek endemic hydrobioids needs to be updated. 

PMID- 24294082
TI  - Taxonomic revision of Madagascan Rhantus (Coleoptera, Dytiscidae, Colymbetinae)
      with an emphasis on Manjakatompo as a conservation priority.
AB  - We review the diving-beetle genus Rhantus Dejean of Madagascar (Coleoptera,
      Dytiscidae, Colymbetinae) based on museum collection holdings and recently
      collected expedition material. Both morphology and DNA is used to test species
      boundaries, in particular whether newly collected material from the Tsaratanana
      mountains in the north represent a new species or are conspecific with Rhantus
      manjakatompo Pederzani and Rocchi 2009, described based on a single male specimen
      from the central Ankaratra mountains. DNA of the holotype of R. manjakatompo was
      successfully extracted in a non-destructive way and sequenced. The general mixed
      Yule coalescent model applied to an ultrametric tree constructed from
      mitochondrial cytochrome c oxidase subunit I (COI) sequence data delimited three
      species. Morphological characters supported the same species unambiguously. We
      therefore recognise three species of Rhantus to occur in Madagascar: R. latus
      (Fairmaire, 1869), R. bouvieri Regimbart, 1900 and R. manjakatompo Pederzani and
      Rocchi, 2009. All three species are endemic to Madagascar and restricted to the
      highlands of the island. Rhantusstenonychus Regimbart, 1895, syn. n., is
      considered a junior synonym of R. latus. We designate lectotypes for R. bouvieri
      and R. goudoti Sharp, 1882, the latter a junior synonym of R. latus. We provide
      descriptions, a determination key, SEM-images of fine pronotal and elytral
      structures, distribution maps, habitus photos, and illustrations of male
      genitalia and pro- and mesotarsal claws. We discuss the role of the Manjakatompo
      forest as a refugium for Madagascan Rhantus diversity and other endemics of the
      montane central high plateau. 

PMID- 24294083
TI  - Four new species of Oidardis Hermann, 1912 (Diptera, Asilidae, Laphriinae,
      Atomosiini) from two major faunistic surveys in the Atlantic Rainforest.
AB  - Two recent faunistic surveys in the Brazilian Atlantic Forests region, the
      PROFAUPAR and the Biota/FAPESP Program, have provided important material for the
      discovery of new taxa from Brazil. We describe herein four new species of robber
      flies of the genus Oidardis (O. falcimystax sp. n., O. fontenellei sp. n., O.
      maculiseta sp. n. and O. marinonii sp. n.), including illustrations and details
      on male hypopygia and female genitalia. A distribution map and a key to the
      species of Oidardis from the Brazilian Atlantic Forests region, including O.
      triangularis (Hermann), 1912, are also provided. 

PMID- 24294084
TI  - Two new species of gorgonian octocorals from the Tropical Eastern Pacific
      Biogeographic Region (Cnidaria, Anthozoa, Gorgoniidae).
AB  - The gorgoniid Eugorgia is exclusively an eastern Pacific genus. It has a wide
      geographic and bathymetric range of distribution, found from California to Peru
      and extends down to 65 m deep. Two new species are herein described. The
      morphological characters were analyzed and illustrated by light and scanning
      electron microscopy. Eugorgia beebei sp. n. can be distinguished by its white,
      ascending, sparse colony growth. Eugorgia mutabilis sp. n. can be distinguished
      by its white colony that changes color after collection, and the conspicuous
      sharp-crested disc sclerites. From a morphological point of view the new species
      are related to the daniana-group, the rubens-group and the siedenburgae-group of
      Eugorgia; their affiliations, and the proposal of a new group are discussed.
      These new species increases the number of species in the genus to 15, and
      contribute to the knowledge of the eastern Pacific octocoral biodiversity. 

PMID- 24294085
TI  - Description of Eucyclops tziscao sp. n., E. angeli sp. n., and a new record of E.
      festivus Lindberg, 1955 (Cyclopoida, Cyclopidae, Eucyclopinae) in Chiapas,
      Mexico.
AB  - Two new species of the freshwater cyclopoid genera Eucyclops are described,
      Eucyclops tziscao sp. n. and E. angeli sp. n. Both species belong to the
      serrulatus-group defined by morphological features such as: the presence of
      distal spinules or hair-like setae (groups N1 and N2) on frontal surface of
      antennal basis; the fourth leg coxa with a strong inner spine that bears dense
      setules on inner side, yet proximally naked (large gap) on outer side; and a 12
      segmented antennule with smooth hyaline membrane on the three distalmost
      segments. Eucyclops tziscao sp. n. is morphologically similar to E. bondi and E.
      conrowae but differs from these species in having a unique combination of
      characters, including a caudal ramus 4.05+/-0.25 times as long as wide, lateral
      seta of Enp3P4 modified as a strong, sclerotized blunt seta, coxal spine of
      fourth leg with inner spinule-like setules distally, and sixth leg of males
      bearing a strong and long inner spine 2.3 times longer than median seta.
      Eucyclops angeli sp. n. can be distinguished by an unique combination of
      morphological features: the short caudal ramus; the long spine on the sixth
      antennular segment of A1; the presence of one additional group of spinules (N12')
      on the caudal surface of A2; the presence of long setae in females, or short
      spinules in males on the lateral margin of fourth prosomite; the strong
      ornamentation of the intercoxal sclerite of P4, specially group I modified as
      long denticles; the distal modified setae of Exp3P3 and Exp3P4 in females and
      males; and the short lateral seta of P5. Finally, we report on a new record of E.
      festivus in Mexico, and add data on morphology of the species. 

PMID- 24294086
TI  - First description of the male of Cryptothele verrucosa L. Koch, 1872 (Araneae),
      the type species of the genus.
AB  - The male of Cryptothele verrucosa L. Koch, 1872, the type species of Cryptothele
      L. Koch, 1872, known from Fiji and Samoa, is described for the first time. It is
      compared with the male of C. alluaudi Simon, 1893, the single properly described
      species of the genus. 

PMID- 24294087
TI  - New species and records of the stonefly genus Neoperla (Plecoptera, Perlidae)
      from Jinhuacha Nature Reserve, Guangxi of China.
AB  - Two new Neoperla species (Neoperla mesospina, Neoperla latispina) are described
      from the adult male stage from the Jinhuacha Nature Reserve, Guangxi of China.
      The new species are compared with similar taxa. Taxonomic remarks are also
      provided for N. transversprojecta Du & Sivec and N. yao Stark. The latter species
      is newly recorded for Guangxi. 

PMID- 24294088
TI  - Taxonomic and morphological survey of the Lygephila lusoria (Linnaeus, 1758)
      species-group with description of a new species (Lepidoptera, Erebidae,
      Toxocampinae).
AB  - The taxa of the Lygephila lusoria (Linnaeus, 1758) species-group are revised. The
      genital features of all known taxa are described and illustrated with special
      reference to the structure of vesica. The male genitalia of L. pallida pallida
      (Bang-Haas, 1907) are described and illustrated for the first time. L. pallida
      subpicata (Wiltshire, 1971) is treated here as a species, L. pallida subpicata
      (Wiltshire, 1971), stat. n., distinct from L. pallida. A new species, L. minima,
      sp. n.,from South Russia is described. Illustrations of the holotype and its
      genitalia are provided; a diagnostic comparison with L. pallida is given. L.
      alaica Remm, 1983 is included in the L. lusoria species-group for the first time.

PMID- 24294089
TI  - First report on the leafhopper genus Balera Young (Hemiptera, Cicadellidae,
      Typhlocybinae, Alebrini) from Argentina, and description of a new species.
AB  - The genus Balera Young is reported for first time to Argentina and a new species
      is described, Balera floripara sp. n. Detailed morphological descriptions and
      illustrations of the new species and a key to males of known species are
      provided. Habralebra amoena is also recorded for the first time from Argentina. 

PMID- 24294090
TI  - Deep phylogenetic divergence between Scolytoplatypus and Remansus, a new genus of
      Scolytoplatypodini from Madagascar (Coleoptera, Curculionidae, Scolytinae).
AB  - Scolytoplatypodini Blandford is a monotypic tribe of ambrosia beetles found in
      Asia, Madagascar and Africa. Only three species are currently known from
      Madagascar and four additional species are here described as new to science.
      Phylogenetic analyses of morphological and molecular data revealed that four of
      the seven endemic species are deeply separated from all other species by genetic
      and distinct morphological characters and therefore placed in a new genus
      Remansus Jordal. The split between this ancient lineage and Scolytoplatypus
      Schaufuss was estimated to approximate Palaeocene age (63 Ma), extending the
      minimum age of ambrosia feeding for this tribe to the beginning of the Palaeocene
      Eocene thermal maximum (PETM). In addition to the ancient origin of Remansus in
      Madagascar during the Palaeocene, a second origin occurred in Scolytoplatypus no
      more than 13 Ma. A geographical origin of the latter in South-Eastern Africa was
      unequivocally inferred from the phylogenies. 

PMID- 24294091
TI  - On five species of the tribes Abacetini and Pterostichini (Coleoptera,
      Carabidae).
AB  - Metabacetus willi sp. n. (type locality: Indonesia, Central Java Province,
      Purworejo Regency, Kaligesing District, cave Seplawan near Donorejo) and
      Rhytiferonia beroni sp. n. (type locality: Papua New Guinea, West Sepik Province,
      Bonforok bil, Tifalmin, 1600 m) are described. Two new combinations: Poecilus
      (Ancholeus) campania (Andrewes, 1937), comb. n. of Feronia campania Andrewes,
      1937, Aristochroa poecilma (Andrewes, 1937), comb. n. of Feronia poecilma
      Andrewes, 1937, and a new synonymy: Pterostichus (Oreophilus) podgoricensis B.
      Gueorguiev, 2013, syn. n. of Pterostichus (Oreophilus) flavofemoratus pinguis
      (Dejean, 1828), are proposed, too. 

PMID- 24294092
TI  - A new genus and eight new species of the subtribe Anillina (Carabidae, Trechinae,
      Bembidiini) from Mexico, with a cladistic analysis and some notes on the
      evolution of the genus.
AB  - One new genus and eight new species of anilline carabids are described from
      southern Mexico. The new genus, Zapotecanillus gen. n., is established for Z.
      oaxacanus (type species) sp. n., Z. nanus sp. n., Z. iviei sp. n., Z. ixtlanus
      sp. n., Z. montanus sp. n., and Z. kavanaughi sp. n. from the Sierra Madre de
      Oaxaca, Z. pecki sp. n. from the Sierra Madre del Sur, and Z. longinoi sp. n.
      from the Sierra Madre de Chiapas. A taxonomic key for all described species of
      Zapotecanillus and a cladistic analysis, based on morphological data, are
      provided. Morphological, behavioral and biogeographical aspects of the speciation
      in the genus obtained from the resulting cladogram are discussed. 

PMID- 24294093
TI  - Three new species of Fufius Simon, 1888 (Araneae, Cyrtaucheniidae) from Brazil
      with the redescription of Fufius funebris Vellard, 1924 and description of the
      female of Fufius lucasae Guadanucci & Indicatti, 2004.
AB  - The mygalomorph neotropical genus Fufius Simon, 1888 comprises ten species,
      distributed from Guatemala in Central America to southeastern Brazil, in South
      America. Most of the species were described from northern South America, in the
      Amazonian region. Only F. funebris Vellard, 1924 and F. lucasae Guadanucci &
      Indicatti, 2004 are known from regions more to the south of the continent. Herein
      we describe three new Brazilian species, Fufius minusculus sp. n. and F.
      jalapensis sp. n. from the state of Tocantins, and F. candango sp. n. from
      Distrito Federal. The female of F. lucasae is described for first time and the
      male and female of F. funebris are redescribed based on specimens collected at
      the type locality. 

PMID- 24294094
TI  - First description of the male of Thaida chepu Platnick, 1987 (Araneae,
      Austrochilidae) with micro-computed tomography of the palpal organ.
AB  - The male of the austrochilid spider Thaida chepu Platnick, 1987 is described for
      the first time. We analyzed the internal anatomy of the palpal organ by using
      micro-computed tomography to investigate the spermophor as well as the muscles
      and tendons in the cymbium and tibia in detail. As shown by our data, muscles 29
      and 30 originate in the tibia and continue with tendons to the base of the bulb,
      which resembles the ancestral organization for the male palp of spiders; this
      condition has not been described for Araneomorphae until now. The 3D
      reconstruction of the spermophor confirms recent interpretations of the male palp
      sclerites within Austrochilidae. 

PMID- 24294095
TI  - Molecular and microscopic analysis of the gut contents of abundant rove beetle
      species (Coleoptera, Staphylinidae) in the boreal balsam fir forest of Quebec,
      Canada.
AB  - Experimental research on beetle responses to removal of logging residues
      following clearcut harvesting in the boreal balsam fir forest of Quebec revealed
      several abundant rove beetle (Staphylinidae) species potentially important for
      long-term monitoring. To understand the trophic affiliations of these species in
      forest ecosystems, it was necessary to analyze their gut contents. We used
      microscopic and molecular (DNA) methods to identify the gut contents of the
      following rove beetles: Atheta capsularis Klimaszewski, Atheta klagesi Bernhauer,
      Oxypoda grandipennis (Casey), Bryophacis smetanai Campbell, Ischnosoma longicorne
      (Maklin), Mycetoporus montanus Luze, Tachinus frigidus Erichson, Tachinus
      fumipennis (Say), Tachinus quebecensis Robert, and Pseudopsis subulata Herman. We
      found no apparent arthropod fragments within the guts; however, a number of fungi
      were identified by DNA sequences, including filamentous fungi and budding yeasts
      [Ascomycota: Candida derodonti Suh & Blackwell (accession number FJ623605),
      Candida mesenterica (Geiger) Diddens & Lodder (accession number FM178362),
      Candida railenensis Ramirez and Gonzales (accession number JX455763), Candida
      sophie-reginae Ramirez & Gonzalez (accession number HQ652073), Candida sp.
      (accession number AY498864), Pichia delftensis Beech (accession number AY923246),
      Pichia membranifaciens Hansen (accession number JQ26345), Pichia misumaiensis Y.
      Sasaki and Tak. Yoshida ex Kurtzman 2000 (accession number U73581), Pichia sp.
      (accession number AM261630), Cladosporium sp. (accession number KF367501),
      Acremoniumpsammosporum W. Gams (accession number GU566287), Alternaria sp.
      (accession number GU584946), Aspergillus versicolor Bubak (accession number
      AJ937750), and Aspergillusamstelodami (L. Mangin) Thom and Church (accession
      number HQ728257)]. In addition, two species of bacteria [Bradyrhizobium japonicum
      (Kirchner) Jordan (accession number BA000040) and Serratia marcescens Bizio
      accession number CP003942] were found in the guts. These results not only provide
      evidence of the consumer-resource relations of these beetles but also clarify the
      relationship between rove beetles, woody debris and fungi. Predominance of yeast
      feeding by abundant rove beetles suggests that it may play an important role in
      their dietary requirements. 

PMID- 24294096
TI  - A revision of the Neotropical genus Paraberismyia Woodley (Diptera,
      Stratiomyidae, Beridinae) with three new species.
AB  - The Neotropical genus Paraberismyia Woodley, 1995, is revised. Three new species,
      P. chiapas sp. n., P. mathisi sp. n., and P. triunfo sp. n. are described, all
      having type localities in Chiapas, Mexico. A key to the four known species is
      provided. 

PMID- 24294097
TI  - Genetic variation corroborates subspecific delimitation in the Namib fog-basking
      beetle, Onymacris unguicularis (Haag) (Tenebrionidae, Coleoptera).
AB  - The fog-basking beetle, Onymacris unguicularis (Haag, 1875), is currently listed
      as a polytypic form comprising two subspecies. A flightless substrate specialist,
      the beetleis endemic to vegetationless dunes in the Namib, where southern
      populations constitute the nominate subspecies, O. u. unguicularis, and
      populations some 300 km to the north compose O. u. schulzeae Penrith, 1984. Their
      taxonomic descriptions are based on minor differences in pronotal and prosternal
      shape, and the phylogenetic validity of these subspecies has yet to be
      ascertained. Here we reassess the polytypic status of O. unguicularis by (1)
      examining diagnostic phenotypic characters in conjunction with a geometric
      morphometric analysis, and (2) conducting phylogenetic analysis of mitochondrial
      DNA sequences. Our results confirm pronotal and prosternal differences, which are
      complemented by geometric morphometric resolution of the subspecies. Phylogenetic
      analysis recovered two reciprocally monophyletic lineages that exhibit perfect
      phylogeographic congruence with phenotypic variation. Our genetic data identify
      southern and northern populations as distinct lineages, corroborate morphometric
      data regarding subspecific delimitation, and therefore support the recognition of
      O. u. unguicularis and O. u. schulzeae as valid taxa under the general lineage
      concept. 

PMID- 24294098
TI  - Two new species and one subspecies of Craniophora Snellen, 1867 (Lepidoptera,
      Noctuidae, Acronictinae) from China.
AB  - Three Craniophora taxa from China, C. fujianensis Kiss and Gyulai, sp. n., C.
      fujianensis hainanensis Kiss and Gyulai, ssp. n. and C. sichuanensis Kiss, Gyulai
      and Saldaitis, sp. n., are newly described. Adult habitus and male genitalia are
      illustrated and compared with those of C. harmandi (Poujade) and C. praeclara
      (Graeser). Females of the new taxa are unknown. 

PMID- 24294099
TI  - Two new species of Abernessia Arle (Pompilidae, Ctenocerinae).
AB  - Two new species are added to the rare pompilid genus Abernessia Arle. Abernessia
      capixaba sp. n. and A. giga sp. n. are described and illustrated. This is the
      first record of the genus from the states of Espirito Santo and Minas Gerais,
      Brazil. The genus now contains four species. A brief discussion of generic
      characters, illustrations, and a key to the known species of Abernessia are
      provided. 

PMID- 24294100
TI  - A catalog of bird specimens associated with Prince Maximilian of Wied-Neuwied and
      potential type material in the natural history collection in Wiesbaden.
AB  - Bird specimens collected by 19(th) century explorer and ornithologist Prince
      Maximilian of Wied-Neuwied form one of the foundation collections of the American
      Museum of Natural History in New York. However, parts of his collection remained
      in Germany and came to the Museum Wiesbaden. Since Wied described numerous new
      species without designating types, some of these specimens might be type
      material. Here we present a catalog of the 30 Wiesbaden specimens associated with
      him and discuss their potential type status. We conclude that 17 individuals in
      11 species are potential type specimens that should be considered in future
      taxonomic work. 

PMID- 24294101
TI  - Revision of the Afrotropical Phaeogenini (Ichneumonidae, Ichneumoninae), with
      description of a new genus and twelve new species.
AB  - We revise the 10 genera and 23 species of the tribe Phaeogenini (Ichneumonidae:
      Ichneumoninae) known to occur in the Afrotropical region. We describe the
      following 13 new taxa: Kibalus Rousse, van Noort & Diller, gen. n.; K. toro
      Rousse, van Noort & Diller, sp. n.; K. mubfs Rousse & van Noort, sp. n.; Arearia
      oxymoron Rousse & van Noort, sp. n.; Chauvinia nyanga Rousse & van Noort, sp. n.;
      Dicaelotus asantesana Rousse & van Noort, sp. n.; D. hoerikwaggoensis Rousse &
      van Noort, sp. n.; D. tablemountainensis Rousse & van Noort, sp. n.; Heterischnus
      mfongosi Rousse & van Noort, sp. n.; H. mkomazi Rousse & van Noort, sp. n.;
      Lusius flummox Rousse & van Noort, sp. n.; Tycherus amatola Rousse & van Noort,
      sp. n.; and T. nardousberg Rousse & van Noort, sp. n. New distribution records:
      Heterischnus africanus (Heinrich, 1936) from South Africa, Tanzania and Uganda;
      H. krausi Schonitzer, 1999 from Rwanda; Lusius tenuissimus (Heinrich, 1938) from
      Democratic Republic of Congo, Malawi, Nigeria, South Africa, and Zimbabwe. A
      doubtful record of Aethecerus foveolatus Gregor, 1940 from Sao Tome is
      additionaly reported in the appendix. We provide illustrated diagnoses and
      identification notes. Online interactive dichotomous and matrix Lucid keys to
      genera and species are available at http://www.waspweb.org. 

PMID- 24294102
TI  - Generalization of value-based attentional priority.
AB  - Attention is the mechanism by which important or salient stimuli are selected for
      perceptual and cognitive processing. Which stimuli are attended has important
      implications for effective goal-directed behaviour, survival, and well-being. A
      growing body of evidence suggests that reward-predicting stimuli capture
      attention involuntarily. In previous studies, value-based attentional priority
      has been observed only when the formerly reward-related stimuli themselves were
      presented as targets or distractors. Here we show that stimulus-reward
      associations learned in one task generalize to different stimuli that share a
      defining feature (colour) in another task. Our results reveal a broad and
      flexible role for reward learning in modulating attentional priority.

PMID- 24294103
TI  - Wild mice as bountiful resources of novel genetic variants for quantitative
      traits.
AB  - Most traits of biological importance, including traits for human complex diseases
      (e.g., obesity and diabetes), are continuously distributed. These complex or
      quantitative traits are controlled by multiple genetic loci called QTLs
      (quantitative trait loci), environments and their interactions. The laboratory
      mouse has long been used as a pilot animal model for understanding the genetic
      architecture of quantitative traits. Next-generation sequencing analyses and
      genome-wide SNP (single nucleotide polymorphism) analyses of mouse genomes have
      revealed that classical inbred strains commonly used throughout the world are
      derived from a few fancy mice with limited and non-randomly distributed genetic
      diversity that occurs in nature and also indicated that their genomes are
      predominantly Mus musculus domesticus in origin. Many QTLs for a huge variety of
      traits have so far been discovered from a very limited gene pool of classical
      inbred strains. However, wild M. musculus mice consisting of five subspecies
      widely inhabit areas all over the world, and hence a number of novel QTLs may
      still lie undiscovered in gene pools of the wild mice. Some of the QTLs are
      expected to improve our understanding of human complex diseases. Using wild M.
      musculus subspecies in Asia as examples, this review illustrates that wild mice
      are untapped natural resources for valuable QTL discovery. 

PMID- 24294105
TI  - Gene-based Genomewide Association Analysis: A Comparison Study.
AB  - The study of gene-based genetic associations has gained conceptual popularity
      recently. Biologic insight into the etiology of a complex disease can be gained
      by focusing on genes as testing units. Several gene-based methods (e.g., minimum
      p-value (or maximum test statistic) or entropy-based method) have been developed
      and have more power than a single nucleotide polymorphism (SNP)-based analysis.
      The objective of this study is to compare the performance of the entropy-based
      method with the minimum p-value and single SNP-based analysis and to explore
      their strengths and weaknesses. Simulation studies show that: 1) all three
      methods can reasonably control the false-positive rate; 2) the minimum p-value
      method outperforms the entropy-based and the single SNP-based method when only
      one disease-related SNP occurs within the gene; 3) the entropy-based method
      outperforms the other methods when there are more than two disease-related SNPs
      in the gene; and 4) the entropy-based method is computationally more efficient
      than the minimum p-value method. Application to a real data set shows that more
      significant genes were identified by the entropy-based method than by the other
      two methods. 

PMID- 24294104
TI  - Regulation of cellulase and hemicellulase gene expression in fungi.
AB  - Research on regulation of cellulases and hemicellulases gene expression may be
      very useful for increasing the production of these enzymes in their native
      producers. Mechanisms of gene regulation of cellulase and hemicellulase
      expression in filamentous fungi have been studied, mainly in Aspergillus and
      Trichoderma. The production of these extracellular enzymes is an energy-consuming
      process, so the enzymes are produced only under conditions in which the fungus
      needs to use plant polymers as an energy and carbon source. Moreover, production
      of many of these enzymes is coordinately regulated, and induced in the presence
      of the substrate polymers. In addition to induction by mono- and oligo
      saccharides, genes encoding hydrolytic enzymes involved in plant cell wall
      deconstruction in filamentous fungi can be repressed during growth in the
      presence of easily metabolizable carbon sources, such as glucose. Carbon
      catabolite repression is an important mechanism to repress the production of
      plant cell wall degrading enzymes during growth on preferred carbon sources. This
      manuscript reviews the recent advancements in elucidation of molecular mechanisms
      responsible for regulation of expression of cellulase and hemicellulase genes in
      fungi. 

PMID- 24294106
TI  - 'From death, lead me to immortality' - mantra of ageing skeletal muscle.
AB  - Skeletal muscle is a post-mitotic tissue maintained by repair and regeneration
      through a population of stem cell-like satellite cells. Following muscle injury,
      satellite cell proliferation is mediated by local signals ensuring sufficient
      progeny for tissue repair. Age-related changes in satellite cells as well as to
      the local and systemic environment potentially impact on the capacity of
      satellite cells to generate sufficient progeny in an ageing organism resulting in
      diminished regeneration. 'Rejuvenation' of satellite cell progeny and
      regenerative capacity by environmental stimuli effectors suggest that a subset of
      age-dependent satellite cell changes may be reversible. Epigenetic regulation of
      satellite stem cells that include DNA methylation and histone modifications which
      regulate gene expression are potential mechanisms for such reversible changes and
      have been shown to control organismal longevity. The area of health and ageing
      that is likely to benefit soonest from advances in the biology of adult stem
      cells is the emerging field of regenerative medicine. Further studies are needed
      to elucidate the mechanisms by which epigenetic modifications regulate satellite
      stem cell function and will require an increased understanding of stem-cell
      biology, the environment of the aged tissue and the interaction between the two. 

PMID- 24294108
TI  - Evolutionary constraints favor a biophysical model explaining hox gene
      collinearity.
AB  - The Hox gene collinearity enigma has often been approached using models based on
      biomolecular mechanisms. The biophysical model is an alternative approach based
      on the hypothesis that collinearity is caused by physical forces pulling the Hox
      genes from a territory where they are inactive to a distinct spatial domain where
      they are activated in a step by step manner. Such Hox gene translocations have
      recently been observed in support of the biophysical model. Genetic engineering
      experiments, performed on embryonic mice, gave rise to several unexpected mutant
      expressions that the biomolecular models cannot predict. On the contrary, the
      biophysical model offers convincing explanation. Evolutionary constraints
      consolidate the Hox clusters and as a result, denser and well organized clusters
      may create more efficient physical forces and a more emphatic manifestation of
      gene collinearity. This is demonstrated by stochastic modeling with white noise
      perturbing the expression of Hox genes. As study cases the genomes of mouse and
      amphioxus are used. The results support the working hypothesis that vertebrates
      have adopted their comparably more compact Hox clustering as a tool needed to
      develop more complex body structures. Several experiments are proposed in order
      to test further the physical forces hypothesis. 

PMID- 24294107
TI  - KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological
      Functions.
AB  - Zinc finger proteins containing the Kruppel associated box (KRAB-ZFPs) constitute
      the largest individual family of transcriptional repressors encoded by the
      genomes of higher organisms. KRAB domain, positioned at the NH2 terminus of the
      KRAB-ZFPs, interacts with a scaffold protein, KAP-1, which is able to recruit
      various transcriptional factors causing repression of genes to which KRAB ZFPs
      bind. The relevance of such repression is reflected in the large number of the
      KRAB zinc finger protein genes in the human genome. However, in spite of their
      numerical abundance little is currently known about the gene targets and the
      physiological functions of KRAB- ZFPs. However, emerging evidence links the
      transcriptional repression mediated by the KRAB-ZFPs to cell proliferation,
      differentiation, apoptosis and cancer. Moreover, the fact that KRAB containing
      proteins are vertebrate-specific suggests that they have evolved recently, and
      that their key roles lie in some aspects of vertebrate development. In this
      review, we will briefly discuss some regulatory functions of the KRAB-ZFPs in
      different physiological and pathological states, thus contributing to better
      understand their biological roles. 

PMID- 24294109
TI  - Speech and Language Disorders in Kenyan Children: Adapting Tools For Regions With
      Few Assessment Resources.
AB  - This study sought to adapt a battery of Western speech and language assessment
      tools to a rural Kenyan setting. The tool was developed for children whose first
      language was KiGiryama, a Bantu language. A total of 539 Kenyan children
      (males=271, females=268, ethnicity=100% Kigiryama. Data were collected from 303
      children admitted to hospital with severe malaria and 206 age-matched children
      recruited from the village communities. The language assessments were based upon
      the Content, Form and Use (C/F/U) model. The assessment was based upon the
      adapted versions of the Peabody Picture Vocabulary Test, Test for the Reception
      of Grammar, Renfrew Action Picture Test, Pragmatics Profile of Everyday
      Communication Skills in Children, Test of Word Finding and language specific
      tests of lexical semantics, higher level language. Preliminary measures of
      construct validity suggested that the theoretical assumptions behind the
      construction of the assessments were appropriate and re-test and inter-rater
      reliability scores were acceptable. These findings illustrate the potential to
      adapt Western speech and language assessments in other languages and settings,
      particularly those in which there is a paucity of standardised tools.

PMID- 24294110
TI  - Triarylmethanols bearing bulky aryl groups and the NOESY/EXSY experimental
      observation of two-ring-flip mechanism for helicity reversal of molecular
      propellers.
AB  - Triarylmethanols - the direct precursors of persistent trityl radicals - are
      racemic mixtures of chiral three-bladed molecular propellers. Depending on
      bulkiness of aryl groups they exhibit various liabilities to interconversion, the
      half- life time of room temperature racemization varying in a range between 8.4
      hours and 1.32 years. NOESY/EXSY experiment performed on two representative
      models strongly supports the two-ring flip mechanism for the configurational
      interchange.

PMID- 24294111
TI  - Reference gene identification for reverse transcription-quantitative polymerase
      chain reaction analysis in an ischemic wound-healing model.
AB  - Reference genes are often used in RT-quantitative PCR (qPCR) analysis to
      normalize gene expression levels to a gene that is expressed stably across study
      groups. They ultimately serve as a control in RT-qPCR analysis, producing more
      accurate interpretation of results. Whereas many reference genes have been used
      in various wound-healing studies, the most stable reference gene for ischemic
      wound-healing analysis has yet to be identified. The goal of this study was to
      determine systematically the most stable reference gene for studying gene
      expression in a rat ischemic wound-healing model using RT-qPCR. Twelve commonly
      used reference genes were analyzed using RT-qPCR and geNorm data analysis to
      determine stability across normal and ischemic skin tissue. It was ultimately
      determined that Ubiquitin C (UBC) and beta-2 Microglobulin (B2M) are the most
      stably conserved reference genes across normal and ischemic skin tissue. UBC and
      B2M represent reliable reference genes for RT-qPCR studies in the rat ischemic
      wound model and are unaffected by sustained tissue ischemia. The geometric mean
      of these two stable genes provides an accurate normalization factor. These
      results provide insight on dependence of reference-gene stability on experimental
      parameters and the importance of such reference-gene investigations. 

PMID- 24294112
TI  - The use of ammonium formate as a mobile-phase modifier for LC-MS/MS analysis of
      tryptic digests.
AB  - A major challenge facing current mass spectrometry (MS)-based proteomics research
      is the large concentration range displayed in biological systems, which far
      exceeds the dynamic range of commonly available mass spectrometers. One approach
      to overcome this limitation is to improve online reversed-phase liquid
      chromatography (RP-LC) separation methodologies. LC mobile-phase modifiers are
      used to improve peak shape and increase sample load tolerance. Trifluoroacetic
      acid (TFA) is a commonly used mobile-phase modifier, as it produces peptide
      separations that are far superior to other additives. However, TFA leads to
      signal suppression when incorporated with electrospray ionization (ESI), and
      thus, other modifiers, such as formic acid (FA), are used for LC-MS applications.
      FA exhibits significantly less signal suppression, but is not as effective of a
      modifier as TFA. An alternative mobile-phase modifier is the combination of FA
      and ammonium formate (AF), which has been shown to improve peptide separations.
      The ESI-MS compatibility of this modifier has not been investigated, particularly
      for proteomic applications. This work compares the separation metrics of mobile
      phases modified with FA and FA/AF and explores the use of FA/AF for the LC-MS
      analysis of tryptic digests. Standard tryptic-digest peptides were used for
      comparative analysis of peak capacity and sample load tolerance. The
      compatibility of FA/AF in proteomic applications was examined with the analysis
      of soluble proteins from canine prostate carcinoma tissue. Overall, the use of
      FA/AF improved online RP-LC separations and led to significant increases in
      peptide identifications with improved protein sequence coverage. 

PMID- 24294113
TI  - Development of a genotyping microarray for studying the role of gene-environment
      interactions in risk for lung cancer.
AB  - A microarray (LungCaGxE), based on Illumina BeadChip technology, was developed
      for high-resolution genotyping of genes that are candidates for involvement in
      environmentally driven aspects of lung cancer oncogenesis and/or tumor growth.
      The iterative array design process illustrates techniques for managing large
      panels of candidate genes and optimizing marker selection, aided by a new
      bioinformatics pipeline component, Tagger Batch Assistant. The LungCaGxE platform
      targets 298 genes and the proximal genetic regions in which they are located,
      using ~ 13,000 DNA single nucleotide polymorphisms (SNPs), which include
      haplotype linkage markers with a minimum allele frequency of 1% and additional
      specifically targeted SNPs, for which published reports have indicated functional
      consequences or associations with lung cancer or other smoking-related diseases.
      The overall assay conversion rate was 98.9%; 99.0% of markers with a minimum
      Illumina design score of 0.6 successfully generated allele calls using genomic
      DNA from a study population of 1873 lung-cancer patients and controls.

PMID- 24294114
TI  - Comparison of protein-extraction methods for gills of the shore crab, Carcinus
      maenas (L.), and application to 2DE.
AB  - As it is well-established that protein extraction constitutes a crucial step for
      two-dimensional electrophoresis (2DE), this work was done as a prerequisite to
      further the study of alterations in the proteome in gills of the shore crab
      Carcinus maenas under contrasted environmental conditions. Because of the
      presence of a chitin layer, shore crab gills have an unusual structure.
      Consequently, they are considered as a hard tissue and represent a challenge for
      optimal protein extraction. In this study, we compared three published extraction
      procedures for subsequent applications to 2DE: the first one uses homogenization
      process, the second one included an additional TCA-acetone precipitation step,
      and finally, the third one associated grinding in liquid nitrogen (N2) and TCA
      acetone precipitation. Extracted proteins were then resolved using 1DE and 2DE.
      Although interesting patterns were obtained using 1DE with the three methods,
      only the one involving grinding in liquid N2 and TCA-acetone precipitation led to
      proper resolution after 2DE, showing a good level of reproducibility at technical
      (85%) and biological (84%) levels. This last method is therefore proposed for
      analysis of gill proteomes in the shore crab. 

PMID- 24294117
TI  - Steven d. Mills, MD.

PMID- 24294115
TI  - A simple method of genomic DNA extraction from human samples for PCR-RFLP
      analysis.
AB  - Isolation of DNA from blood and buccal swabs in adequate quantities is an
      integral part of forensic research and analysis. The present study was performed
      to determine the quality and the quantity of DNA extracted from four commonly
      available samples and to estimate the time duration of the ensuing PCR
      amplification. Here, we demonstrate that hair and urine samples can also become
      an alternate source for reliably obtaining a small quantity of PCR-ready DNA. We
      developed a rapid, cost-effective, and noninvasive method of sample collection
      and simple DNA extraction from buccal swabs, urine, and hair using the phenol
      chloroform method. Buccal samples were subjected to DNA extraction, immediately
      or after refrigeration (4-6 degrees C) for 3 days. The purity and the
      concentration of the extracted DNA were determined spectrophotometerically, and
      the adequacy of DNA extracts for the PCR-based assay was assessed by amplifying a
      1030-bp region of the mitochondrial D-loop. Although DNA from all the samples was
      suitable for PCR, the blood and hair samples provided a good quality DNA for
      restriction analysis of the PCR product compared with the buccal swab and urine
      samples. In the present study, hair samples proved to be a good source of genomic
      DNA for PCR-based methods. Hence, DNA of hair samples can also be used for the
      genomic disorder analysis in addition to the forensic analysis as a result of the
      ease of sample collection in a noninvasive manner, lower sample volume
      requirements, and good storage capability. 

PMID- 24294118
TI  - Trauma, bowel obstruction, and colorectal emergencies.

PMID- 24294120
TI  - Management of colonic obstruction: a review.
AB  - Large bowel obstruction is a common problem with many different causes, the most
      common being colorectal adenocarcinoma, extracolonic adenocarcinoma, diverticular
      disease, volvulus, and inflammatory bowel disease. The nature of the obstruction
      can influence the best management. Historically, treatment of obstruction
      consisted of surgical removal of the obstruction if possible and decompression of
      the bowel with an ostomy. Other strategies for managing obstruction have evolved
      as alternatives to stomas, including primary resection with anastomosis and
      endoscopic stent placement. The choice of treatment can therefore be tailored to
      the individual patient with good success. 

PMID- 24294119
TI  - Historical and current trends in colon trauma.
AB  - The authors discuss the evolution of the evaluation and management of colonic
      trauma, as well as the debate regarding primary repair versus fecal diversion.
      Their evidence-based review covers diagnosis, management, surgical approaches,
      and perioperative care of patients with colon-related trauma. The management of
      traumatic colon injuries has evolved significantly over the past 50 years; here
      the authors describe a practical approach to the treatment and management of
      traumatic injuries to the colon based on the most current research. However,
      management of traumatic colon injuries remains a challenge and continues to be
      associated with significant morbidity. Familiarity with the different methods to
      the approach and management of colonic injuries will allow surgeons to minimize
      unnecessary complications and mortality. 

PMID- 24294121
TI  - Surgical Management of Clostridium difficile Colitis.
AB  - Clostridium difficile infection (CDI) will progress to fulminant disease in 3 to
      5% of cases. With the emergence of hypervirulent, multidrug-resistant strains,
      the incidence and severity of disease are continuing to rise. Prompt
      identification, early resuscitation, and treatment are critical in preventing
      morbidity and mortality in this increasingly common condition. Discontinuation of
      antibiotics and treatment with oral vancomycin and intravenous or oral
      metronidazole are first-line treatments, but complicated cases may require
      surgery. Subtotal colectomy with ileostomy remains the standard of care when
      toxic megacolon, perforation, or an acute surgical abdomen is present, but
      mortality rates are high. Recognition of risk factors for fulminant CDI and
      earlier surgical intervention may decrease mortality from this highly lethal
      disease. 

PMID- 24294122
TI  - Care of the patient with anorectal trauma.
AB  - Blunt and penetrating injuries to the anus and rectum are uncommon. Considerable
      debate remains regarding the optimal treatment of rectal injuries. Although
      intraperitoneal rectal injuries can be treated similarly to colonic injuries,
      treatment options for extraperitoneal injuries include fecal diversion with a
      colostomy, presacral drainage, repair of the rectal defect, and distal rectal
      washout. Perineal injuries resulting in anal sphincter disruption often occur
      with severe associated injuries. Small defects can be repaired primarily, but
      extensive injuries often require diversion and sphincter reconstruction. 

PMID- 24294123
TI  - Rectal foreign bodies: what is the current standard?
AB  - Rectal foreign bodies represent a challenging and unique field of colorectal
      trauma. The approach includes a careful history and physical examination, a high
      index of suspicion for any evidence of perforation, a creative approach to
      nonoperative removal, and appropriate short-term follow-up to detect any delayed
      perforation. 

PMID- 24294124
TI  - Current treatment of lower gastrointestinal hemorrhage.
AB  - Massive lower gastrointestinal bleeding is a significant and expensive problem
      that requires methodical evaluation, management, and treatment. After initial
      resuscitation, care should be taken to localize the site of bleeding. Once
      localized, lesions can then be treated with endoscopic or angiographic
      interventions, reserving surgery for ongoing or recurrent bleeding. 

PMID- 24294125
TI  - Management of ischemic colitis.
AB  - Ischemic colitis is a commonly misunderstood clinical condition. Although the
      colon is the most common region of ischemia in the gastrointestinal tract, many
      surgeons have difficulty with diagnosis and treatment of ischemic colitis. The
      process can occur from either occlusive vascular disease or nonocclusive disease,
      and can be gangrenous or nongangrenous. Differentiating gangrenous from
      nongangrenous disease can be a difficult clinical challenge as both sets of
      patients generally present with abdominal pain and bloody diarrhea. Although the
      majority of patients have transient ischemia with nongangrenous colitis that can
      be successfully managed nonoperatively, prompt recognition and surgical
      intervention is critical in patients with gangrenous colitis. In this article,
      the diagnosis and treatment of ischemic colitis is reviewed with emphasis on a
      systematic, evidence-based approach to management. 

PMID- 24294126
TI  - Management of colonic volvulus.
AB  - Colonic volvulus is a common cause of large bowel obstruction worldwide. It can
      affect all parts of the colon, but most commonly occurs in the sigmoid and cecal
      areas. This disease has been described for centuries, and was studied by
      Hippocrates himself. Currently, colonic volvulus is the third most common cause
      of large bowel obstruction worldwide, and is responsible for ~15% of large bowel
      obstructions in the United States. This article will discuss the history of
      colonic volvulus, and the predisposing factors that lead to this disease.
      Moreover, the epidemiology and diagnosis of each type of colonic volvulus, along
      with the various treatment options will be reviewed. 

PMID- 24294127
TI  - Using the Social Enterprise Intervention (SEI) and Individual Placement and
      Support (IPS) models to improve employment and clinical outcomes of homeless
      youth with mental illness.
AB  - Prior research reveals high unemployment rates among homeless youth. The
      literature offers many examples of using evidence-informed and evidence-based
      supported employment models with vulnerable populations to assist them in
      obtaining and maintaining employment and concurrently addressing mental health
      challenges. However, there are few examples to date of these models with homeless
      youth with mental illness. The purpose of this article was thus to describe a
      methodology for establishing a university-agency research partnership to design,
      implement, evaluate, and replicate evidence-informed and evidence-based
      interventions with homeless youth with mental illness to enhance their
      employment, mental health, and functional outcomes. Data from two studies are
      used to illustrate the relationship between vocational skill-building/employment
      and mental health among homeless youth. The article concludes with a discussion
      of the implications of conducting community-based participatory employment and
      clinical intervention research. The author highlights the opportunities and
      tensions associated with this approach.

PMID- 24294128
TI  - Fathers' Contributions to Housework and Childcare and Parental Aggravation Among
      First-Time Parents.
AB  - This study investigated the associations between fathers' contributions to
      housework and childcare and both spouses' parenting aggravation. It was
      hypothesized that greater father contributions to domestic labor would be
      associated with more paternal aggravation but less maternal aggravation. Data are
      from a four-wave study of 178 married couples undergoing the transition to first
      parenthood. Dyadic growth-curve models revealed gender differences in aggravation
      trajectories over the first year of the child's life. Fathers were higher in
      initial aggravation, but mothers' aggravation grew at a faster rate over time.
      The primary hypothesis was only partially supported. Fathers' contributions to
      childcare were associated with significantly lower maternal aggravation levels,
      but only among more religious mothers. Child fussiness and unpredictability were
      consistently significant predictors of higher aggravation for both parents.
      Depressive symptomatology was positively related to aggravation for fathers,
      whereas love for the spouse was associated with lower aggravation for mothers,
      controlling for other factors.

PMID- 24294129
TI  - Comparative evaluation of agroindustrial byproducts for the production of
      alkaline protease by wild and mutant strains of Bacillus subtilis in submerged
      and solid state fermentation.
AB  - The present study describes the screening of different agroindustrial byproducts
      for enhanced production of alkaline protease by a wild and EMS induced mutant
      strain of Bacillus subtilis IH-72(EMS8). During submerged fermentation, different
      agro-industrial byproducts were tested which include defatted seed meals of rape,
      guar, sunflower, gluten, cotton, soybean, and gram. In addition to these meals,
      rice bran, wheat bran, and wheat flour were also evaluated for protease
      production. Of all the byproducts tested, soybean meal at a concentration of 20
      g/L gave maximum production of the enzyme, that is, 5.74  +/-  0.26 U/mL from
      wild and 11.28  +/-  0.45 U/mL from mutant strain, during submerged fermentation.
      Different mesh sizes (coarse, medium, and fine) of the soybean meal were also
      evaluated, and a finely ground soybean meal (fine mesh) was found to be the best.
      In addition to the defatted seed meals, their alkali extracts were also tested
      for the production of alkaline protease by Bacillus subtilis, but these were
      proved nonsignificant for enhanced production of the enzyme. The production of
      the enzyme was also studied in solid state fermentation, and different agro
      industrial byproducts were also evaluated for enzyme production. Wheat bran
      partially replaced with guar meal was found as the best substrate for maximum
      enzyme production under solid state fermentation conditions.

PMID- 24294130
TI  - Efficient and convenient synthesis of 1,8-dioxodecahydroacridine derivatives
      using Cu-doped ZnO nanocrystalline powder as a catalyst under solvent-free
      conditions.
AB  - A simple and convenient one-step method for synthesis of acridines and their
      derivatives from condensation of aromatic aldehydes, cyclic diketones, and aryl
      amines using Cu-doped ZnO nanocrystalline powder as a catalyst is reported. The
      present protocol provides several advantages such as good yields, short reaction
      time, easy workup, and simplicity in operation. 

PMID- 24294131
TI  - A novel approach to word sense disambiguation based on topical and semantic
      association.
AB  - Word sense disambiguation (WSD) is a fundamental problem in nature language
      processing, the objective of which is to identify the most proper sense for an
      ambiguous word in a given context. Although WSD has been researched over the
      years, the performance of existing algorithms in terms of accuracy and recall is
      still unsatisfactory. In this paper, we propose a novel approach to word sense
      disambiguation based on topical and semantic association. For a given document,
      supposing that its topic category is accurately discriminated, the correct sense
      of the ambiguous term is identified through the corresponding topic and semantic
      contexts. We firstly extract topic discriminative terms from document and
      construct topical graph based on topic span intervals to implement topic
      identification. We then exploit syntactic features, topic span features, and
      semantic features to disambiguate nouns and verbs in the context of ambiguous
      word. Finally, we conduct experiments on the standard data set SemCor to evaluate
      the performance of the proposed method, and the results indicate that our
      approach achieves relatively better performance than existing approaches. 

PMID- 24294132
TI  - Multidimensional scaling analysis of the dynamics of a country economy.
AB  - This paper analyzes the Portuguese short-run business cycles over the last 150
      years and presents the multidimensional scaling (MDS) for visualizing the
      results. The analytical and numerical assessment of this long-run perspective
      reveals periods with close connections between the macroeconomic variables
      related to government accounts equilibrium, balance of payments equilibrium, and
      economic growth. The MDS method is adopted for a quantitative statistical
      analysis. In this way, similarity clusters of several historical periods emerge
      in the MDS maps, namely, in identifying similarities and dissimilarities that
      identify periods of prosperity and crises, growth, and stagnation. Such features
      are major aspects of collective national achievement, to which can be associated
      the impact of international problems such as the World Wars, the Great
      Depression, or the current global financial crisis, as well as national events in
      the context of broad political blueprints for the Portuguese society in the
      rising globalization process. 

PMID- 24294133
TI  - Transcriptional regulation of Delta6-desaturase by peroxisome proliferative
      activated receptor delta agonist in human pancreatic cancer cells: role of
      MEK/ERK1/2 pathway.
AB  - The Delta6-desaturase (Delta6D), also known as fatty acid desaturase 2, is a
      regulatory enzyme in de novo fatty acid synthesis, which has been linked to
      obesity and diabetes. The aim of the present study was to investigate the effect
      of peroxisome proliferative-activated receptor delta (PPAR delta ) agonist and
      MEK/ERK1/2-dependent pathway on the expression of Delta6D in human pancreatic
      carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to
      the commonly used ERK1/2 pathway inhibitor PD98059 and PPAR delta agonist GW0742.
      Changes in mRNA and protein expression of Delta6D were then determined using real
      time RT-PCR and Western blot, respectively. The expression of Delta6D (P < 0.01)
      increased following treatment with PPAR delta agonist both at mRNA and protein
      levels, whereas no significant change was observed after treatment with
      MEK/ERK1/2 pathway inhibitor. It was also found that the increase in the
      expression of Delta6D in response to GW0742 was significantly inhibited by
      PD98059 (>40%, P < 0.05) or EGF receptor-selective inhibitor AG1478 (>25%, P <
      0.05) pretreatment. PPAR delta and MEK/ERK1/2 signaling pathways affect
      differentially the expression of Delta6D in pancreatic cancer cells. Furthermore,
      there may be an inhibitory crosstalk between these two regulatory pathways on the
      mRNA expression of Delta6D and subsequently on Delta6D protein expression. 

PMID- 24294135
TI  - Full glowworm swarm optimization algorithm for whole-set orders scheduling in
      single machine.
AB  - By analyzing the characteristics of whole-set orders problem and combining the
      theory of glowworm swarm optimization, a new glowworm swarm optimization
      algorithm for scheduling is proposed. A new hybrid-encoding schema combining with
      two-dimensional encoding and random-key encoding is given. In order to enhance
      the capability of optimal searching and speed up the convergence rate, the
      dynamical changed step strategy is integrated into this algorithm. Furthermore,
      experimental results prove its feasibility and efficiency. 

PMID- 24294134
TI  - Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico
      predictions, and molecular studies.
AB  - Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty
      acid oxidation characterized by hypoglycemic crisis under fasting or during
      stress conditions, leading to lethargy, seizures, brain damage, or even death.
      Biochemical acylcarnitines data obtained through newborn screening by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular
      analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000
      newborns screened, we identified 14 MCADD patients, in whom, by molecular
      analysis, we found a new nonsense c.823G>T (p.Gly275*) and two new missense
      mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics
      predictions based on both phylogenetic conservation and functional/structural
      software were used to characterize the new identified variants. Our findings
      confirm the rising incidence of MCADD whose existence is increasingly recognized
      due to the efficacy of an expanded newborn screening panel by LC-MS/MS making
      possible early specific therapies that can prevent possible crises in at-risk
      infants. We noticed that the "common" p.Lys329Glu mutation only accounted for 32%
      of the defective alleles, while, in clinically diagnosed patients, this mutation
      accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are
      especially critical when considering screening programs. The functional and
      pathogenic characterization of genetic variants presented here is required to
      predict their medical consequences in newborns. 

PMID- 24294137
TI  - Deliberations on the external morphology and modification of the labial segments
      in the Nepomorpha (Heteroptera: Insecta) with notes on the phylogenetic
      characteristics.
AB  - The present study provides new data concerning the external morphology of the
      labial segments of 46 species from nine Nepomorpha families using the scanning
      electron microscope. The labial segments are described in detail and images of
      their structures are presented for the systematic groups. Subsequent segments of
      the labium (I, II, III, and IV) are shaped similarly in all investigated taxa but
      carry individual characters in some (sub-)families. Five morphologically distinct
      forms of the apical plate and five intercalary sclerites have been identified.
      Additionally, three types of the articulation on the dorsal side between the
      third and second segments are interpreted as the new characters. The presence of
      the midventral condyle on the distal edge of the first segment and the third
      segment has been reanalyzed. New position of the midventral condyle on the
      proximal edge of the fourth labial segment has been distinguished in several
      groups. The new set of characters has been estimated from the plesiomorphic taxa
      of the Nepoidea (Nepidae and Belostomatidae) and subsequently through the more
      advanced taxa in the relation to the outgroup (Gerromorpha). The evaluation of
      these characters has revealed twenty-seven new apomorphies for the labium in the
      Nepomorpha. 

PMID- 24294136
TI  - A high-fat diet enriched with low omega-6 to omega-3 fatty acid ratio reduced fat
      cellularity and plasma leptin concentration in Sprague-Dawley rats.
AB  - This study was aimed to investigate the effects of dietary fatty acids on the
      accretion pattern of major fat pads, inguinal fat cellularity, and their relation
      with plasma leptin concentration. Forty Sprague-Dawley rats were randomly
      assigned into four groups and received the following diets for 22 weeks: (1)
      standard rat chow diet (CTRL), (2) CTRL + 10% (w/w) butter (HFAR), (3) CTRL +
      3.33% (w/w) menhaden fish oil + 6.67% (w/w) soybean oil (MFAR), and (4) CTRL +
      6.67% (w/w) menhaden fish oil + 3.33% (w/w) soybean oil (LFAR). Inguinal fat
      cellularity and plasma leptin concentration were measured in this study. Results
      for inguinal fat cellularity showed that the mean adipocyte number for the MFAR
      (9.2 * 105 +/- 3.6) and LFAR (8.5 * 105 +/- 5.1) groups was significantly higher
      (P < 0.05) than the rest, while the mean adipocyte diameter of HFAR group was
      larger (P < 0.05) (46.2 +/- 2.8) than the rest. The plasma leptin concentration
      in the HFAR group was higher (P < 0.05) (3.22 +/- 0.32 ng/mL), than the other
      groups. The higher inguinal fat cellularity clearly indicated the ability of the
      polyunsaturated fatty acids (PUFA) and butter supplemented diets to induce
      hyperplasia and hypertrophy of fat cells, respectively, which caused adipocyte
      remodeling due to hyperleptinemia.

PMID- 24294138
TI  - Evaluation of arterial stiffness for predicting future cardiovascular events in
      patients with ST segment elevation and non-ST segment elevation myocardial
      infarction.
AB  - BACKGROUND: Arterial stiffness parameters in patients who experienced MACE after
      acute MI have not been studied sufficiently. We investigated arterial stiffness
      parameters in patients with ST segment elevation (STEMI) and non-ST segment
      elevation myocardial infarction (NSTEMI). METHODS: Ninety-four patients with
      acute MI (45 STEMI and 49 NSTEMI) were included in the study. Arterial stiffness
      was assessed noninvasively by using TensioMed Arteriograph. RESULTS: Arterial
      stiffness parameters were found to be higher in NSTEMI group but did not achieve
      statistical significance apart from pulse pressure (P = 0.007). There was no
      significant difference at MACE rates between two groups. Pulse pressure and heart
      rate were also significantly higher in MACE observed group. Aortic pulse wave
      velocity (PWV), aortic augmentation index (AI), systolic area index (SAI), heart
      rate, and pulse pressure were higher; ejection fraction, the return time (RT),
      diastolic reflex area (DRA), and diastolic area index (DAI) were significantly
      lower in patients with major cardiovascular events. However, PWV, heart rate, and
      ejection fraction were independent indicators at development of MACE.
      CONCLUSIONS: Parameters of arterial stiffness and MACE rates were similar in
      patients with STEMI and NSTEMI in one year followup. The independent prognostic
      indicator aortic PWV may be an easy and reliable method for determining the risk
      of future events in patients hospitalized with acute MI.

PMID- 24294140
TI  - Performance evaluation and microstructure characterization of metakaolin-based
      geopolymer containing oil palm ash.
AB  - This study reports on the microstructure, compressive strength, and drying
      shrinkage of metakaolin (MK) based geopolymers produced by partially replacing MK
      by oil palm ash (OPA). The OPA was used as raw material producing different molar
      ratios of SiO2/Al2O3 and CaO/SiO2. The geopolymer samples were cured at 80
      degrees C for 1, 2, or 4 hours and kept at ambient temperature until testing. The
      compressive strength was measured after 2, 6, and 24 hours and 7 and 28 days. The
      testing results revealed that the geopolymer with 5% OPA (SiO2  : Al2O3 = 2.88 :
      1) gave the highest compressive strength. Scanning electron microscopy (SEM)
      indicated that the 5% OPA sample had a dense-compact matrix and less unreacted
      raw materials which contributed to the higher compressive strength. In the X-ray
      diffraction (XRD) patterns, the change of the crystalline phase after heat curing
      for 4 hours was easily detectable compared to the samples subjected to a shorter
      period of heat curing.

PMID- 24294139
TI  - Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies
      in systemic lupus erythematosus.
AB  - Little information exists about the association of anti-SSA/Ro60 and anti
      Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we
      analysed the associations of both anti-Ro reactivities with clinical and
      immunological manifestations in 141 SLE patients. Photosensitivity and
      xerophtalmia/xerostomia were found to be positively associated with both anti
      SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P =
      0.022, resp.). In contrast, a negative association was detected regarding anti
      phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than
      anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with
      hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas
      anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon
      (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA
      (P = 0.013). Lymphocytes are involved in the relationship between anti
      Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than
      negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21
      showed both common and specific associations in SLE. These data thus increase
      evidence of the different associations of the two anti-Ro specificities even in a
      particular disease. 

PMID- 24294141
TI  - Synthesis and use of [Cd(Detu)2(OOCCH3)2].H2O as single molecule precursor for
      Cds nanoparticles.
AB  - Substituted thiourea ligands are of interest because they possess various donor
      sites for metal ions and their application in separation of metal ions and as
      antimicrobial agents. The coordination of the sulfur donor atom led to interest
      in them as precursor for semiconductor nanoparticles. In this study, cadmium(II)
      complex of diethylthiourea was synthesized and characterized by elemental
      analysis, FTIR, and X-ray crystallography. Single crystal X-ray structure of the
      complex showed that the octahedral geometry around the Cd ion consists of two
      molecules of diethylthiourea acting as monodentate ligands and two chelating
      acetate ions. The thermal decomposition of the compound showed that it decomposed
      to give CdS. The compound was thermolysed in hexadecylamine (HDA) to prepare HDA
      capped CdS nanoparticles. The absorption spectrum showed blue shifts in its
      absorption band edges which clearly indicated quantum confinement effect, and the
      emission spectrum showed characteristic band edge luminescence. The broad
      diffraction peaks of the XRD pattern showed the materials to be of the nanometric
      size. 

PMID- 24294142
TI  - Lateral inhibition in accumulative computation and fuzzy sets for human fall
      pattern recognition in colour and infrared imagery.
AB  - Fall detection is an emergent problem in pattern recognition. In this paper, a
      novel approach which enables to identify a type of a fall and reconstruct its
      characteristics is presented. The features detected include the position previous
      to a fall, the direction and velocity of a fall, and the postfall inactivity.
      Video sequences containing a possible fall are analysed image by image using the
      lateral inhibition in accumulative computation method. With this aim, the region
      of interest of human figures is examined in each image, and geometrical and
      kinematic characteristics for the sequence are calculated. The approach is valid
      in colour and in infrared video. 

PMID- 24294143
TI  - Are Koreans prepared for the rapid increase of the single-household elderly? Life
      satisfaction and depression of the single-household elderly in Korea.
AB  - PURPOSE: In Korea, it has been estimated that the number of the single-household
      elderly increased 45% from 2005 to 2010. This research was conducted to provide
      empirical resources for development of a community mental health program by an
      explorative investigation on depression, coping mechanism, and life satisfaction
      of a single-household elderly population. DESIGN AND METHODS: This research
      applied a descriptive survey research design. Participants were 225 single
      household elderlies residing in Seoul, Korea. The geriatric depression scale and
      the satisfaction with life scale were used to check the level of depression and
      life satisfaction of the participants. RESULTS: Results showed that 46.3 percent
      of the participants were categorized as having light-to-severe level of
      depression, and 80.5 percent of the participants responded that they were
      dissatisfied with their lives. This research demonstrated that the level of
      depression and life satisfaction of the Korean single-household elderly is
      statistically significantly related to age and gender as well as coping resources
      and human resources. IMPLICATIONS: Current public health services in Korea for
      the single-household elderly are still lacking and require active support,
      intervention, and research to provide effective programs and services. Case
      management, counseling, and various programs based on Korean culture including
      support from family members and community-based assistance are recommended to
      help the vulnerable population.

PMID- 24294144
TI  - A Semi-Automated Positioning System for contact-mode Atomic Force Microscopy
      (AFM).
AB  - Contact mode Atomic Force Microscopy (CM-AFM) is popularly used by the biophysics
      community to study mechanical properties of cells cultured in petri dishes, or
      tissue sections fixed on microscope slides. While cells are fairly easy to
      locate, sampling in spatially heterogeneous tissue specimens is laborious and
      time-consuming at higher magnifications. Furthermore, tissue registration across
      multiple magnifications for AFM-based experiments is a challenging problem,
      suggesting the need to automate the process of AFM indentation on tissue. In this
      work, we have developed an image-guided micropositioning system to align the AFM
      probe and human breast-tissue cores in an automated manner across multiple
      magnifications. Our setup improves efficiency of the AFM indentation experiments
      considerably. Note to Practitioners: Human breast tissue is by nature
      heterogeneous, and in the samples we studied, epithelial tissue is formed by
      groups of functional breast epithelial cells that are surrounded by stromal
      tissue in a complex intertwined way. Therefore sampling a specific cell type on
      an unstained specimen is very difficult. To aid us, we use digital stained images
      of the same tissue annotated by a certified pathologist to identify the region of
      interest (ROI) at a coarse magnification and an image-guided positioning system
      to place the unstained tissue near the AFM probe tip. Using our setup, we could
      considerably reduce AFM operating time and we believe that our setup is a viable
      supplement to commercial AFM stages with limited X-Y range.

PMID- 24294145
TI  - Group Process in the single-gender Women's Recovery Group compared with mixed
      gender Group Drug Counseling.
AB  - Enhanced affiliation among members is thought to provide increased support for
      women in single-gender compared with mixed-gender group therapy for substance use
      disorders (SUDs) and to provide a potential mechanism of action for its efficacy.
      In a Stage I trial of single-gender versus mixed-gender group therapy for SUDs we
      examined affiliative statements made by members in two group treatments, single
      gender Women's Recovery Group (WRG) and mixed-gender Group Drug Counseling (GDC).
      Twenty-eight WRG and 17 GDC group therapy tapes were coded and compared for five
      types of affiliative statements. Three types of affiliative statements
      (agreement, supportive, and completing a thought) were highly correlated and were
      more frequent in WRG than GDC (D=0.882, p=0.27). In GDC, women were more likely
      to provide an affiliative statement to a male group member than any other
      combination of directionality (p<0.01). Compared with mixed-gender, single-gender
      group therapy for SUDs may enhance support through greater frequency of
      affiliative statements.

PMID- 24294146
TI  - Blood pressure changes in African American patients receiving chiropractic care
      in a teaching clinic: a preliminary study.
AB  - OBJECTIVE: The purpose of this preliminary study was to determine if a course of
      chiropractic care would change blood pressure measurements in African American
      patients and to determine if a study was feasible in a chiropractic teaching
      clinic. METHODS: Twenty-four African American patients received chiropractic care
      in a chiropractic teaching clinic over a study period that spanned 23 visits for
      each patient. Inclusion criteria consisted of patients having a diagnosis of
      prehypertension (120-139/80-89) or hypertension stage 1 (140-159/90-99). The mean
      values of 3 baseline blood pressure readings were compared with the mean values
      of blood pressure readings taken on visits 21, 22, and 23. RESULTS: For the
      entire sample, reductions for both systolic and diastolic blood pressures were
      not statistically significant (P > .07). When 4 patients having body mass index
      values that were considered as outliers were excluded, a statistically
      significant decrease in diastolic blood pressure was observed (P = .004). By
      group, a statistically significant reduction occurred in the hypertension stage 1
      group for systolic and diastolic blood pressures. CONCLUSION: This study showed
      that research of this nature may be feasible in chiropractic teaching clinics.
      The preliminary findings of this study showed that, for a subgroup of African
      American patients receiving chiropractic care, blood pressure decreased for (a)
      hypertension stage 1 patients and (b) the sample when those with excessive body
      mass index were excluded.

PMID- 24294147
TI  - Chiropractic care using a functional neurologic approach for idiopathic cervical
      dystonia in a 59-year-old woman.
AB  - OBJECTIVE: The purpose of this case report is to describe the care and outcomes
      of a patient with cervical dystonia who was treated using chiropractic and other
      alternative medicine interventions. CLINICAL FEATURES: A 59-year-old woman had an
      11-year history of cervical dystonia. She had an uncontrollable 60 degrees 
      leftward head rotation upon shutting her eyes and had spasmodic contractions that
      caused fatigue. INTERVENTION AND OUTCOME: The management consisted of blue-lensed
      glasses, vibration stimulation, spinal manipulation, and eye-movement exercises.
      Within the first week of treatment, she had a reduction in symptoms, which was
      documented using a functional numeric scale, and improved posture, which was
      assessed using measurements from her midsternal line to the center of her chin.
      CONCLUSION: This patient with cervical dystonia responded to the use of
      conservative, nonpharmacological treatment procedures that consisted of
      chiropractic care using a functional neurologic approach aimed at improving her
      spasmodic contractions and function.

PMID- 24294148
TI  - Chiropractic management of a patient with ulnar nerve compression symptoms: a
      case report.
AB  - OBJECTIVE: The purpose of this case report is to describe chiropractic management
      of a patient with arm and hand numbness and who was suspected to have ulnar nerve
      compression. CLINICAL FEATURES: A 41-year-old woman presented with hand weakness
      and numbness along the medial aspect of her right forearm and the 3 most medial
      fingers. The onset of symptoms presented suddenly, 3 weeks prior, when she woke
      up in the morning and assumed she had "slept wrong." The patient's posture showed
      protracted shoulders and moderate forward head carriage. Orthopedic assessment
      revealed symptomatic right elevated arm stress test, grip strength asymmetry, and
      a Tinel sign at the right cubital tunnel. INTERVENTION AND OUTCOME: The patient
      was treated using chiropractic care, which consisted of manipulative therapy,
      myofascial therapy, and elastic therapeutic taping. Active home care included
      performing postural exercises and education about workstation ergonomics. She
      demonstrated immediate subjective improvement of her numbness and weakness after
      the first treatment. Over a series of 11 treatments, her symptoms resolved
      completely; and she was able to perform work tasks without dysfunction.
      CONCLUSION: Chiropractic treatment consisting of manipulation, soft tissue
      mobilizations, exercise, and education of workstation ergonomics appeared to
      reduce the symptoms of ulnar nerve compression symptoms for this patient.

PMID- 24294149
TI  - Breech repositioning unresponsive to Webster technique: coexistence of
      oligohydramnios.
AB  - OBJECTIVE: The purpose of this report is to describe the results of a pregnant
      woman demonstrating breech fetal presentation who was managed with Webster
      technique in the presence of oligohydramnios. CLINICAL FEATURES: A 23-year-old
      primigravida woman sought chiropractic care for the management of breech
      presentation and bilateral sacroiliac arthralgia at 34 weeks' gestation.
      INTERVENTION AND OUTCOME: Sacral manipulation and abdominal effleurage (Webster
      Technique) was used to address breech presentation and sacroiliac arthralgia for
      a total of 7 treatments over a 3 1/2-week duration. The patient's sacroiliac pain
      reduced from 8/10 to 3/10. However, breech presentation was unchanged at each
      treatment. At a scheduled prenatal surveillance during the 37th week of
      gestation, the midwife detected vaginal bleeding and reduced fundal height, which
      resulted in hospitalization, diagnosis of oligohydramnios, and an emergency
      cesarean delivery. CONCLUSION: For this particular patient, the breech
      presentation was not corrected using the Webster technique. Clinicians who use
      the Webster technique to manage breech fetal presentation should be aware of
      undiagnosed comorbidities as a complicating factor in clinical presentation.
      Screening for previously undiagnosed comorbidities, such as oligohydramnios, must
      be considered.

PMID- 24294151
TI  - Abstracts of the Scientific Sessions from the WFC'S 12th Biennial Congress
      Proceedings, Durban, South Africa, April 10-13, 2013.

PMID- 24294150
TI  - Management of trapeziometacarpal osteoarthritis pain and dysfunction using
      mobilization with movement technique in combination with kinesiology tape: a case
      report.
AB  - OBJECTIVE: The purpose of this report is to describe the management of a patient
      with advanced trapeziometacarpal (TMC) osteoarthritis (OA) using mobilization
      with movement technique in combination with kinesiology tape to decrease pain and
      improve range of motion. CLINICAL FEATURES: A 52-year-old female seamstress (a
      career of 35 years' duration) presented to a physiotherapy clinic with pain in
      the dorsal aspect of the thumb carpometacarpal region of the right (dominant)
      hand. Examination revealed reduced ability to abduct the right thumb, significant
      loss of web space, weakness of pinch grip, and deterioration of hand function.
      Radiographs demonstrated OA of the TMC stage IV according to the Eaton-Littler
      Burton classification, with instability and subluxation of the joint.
      INTERVENTION AND OUTCOME: A combined treatment protocol of mobilization with
      movement and kinesiology tape at the TMC joint for 12 weekly sessions was
      performed. Outcome measures were assessed at baseline, immediately upon
      completion of treatment, and at 2-month follow-up and included numeric pain
      rating scale, range of motion, pressure pain threshold, and tip pinch strength at
      the TMC joint. Treatment interventions were applied for 12 sessions over a period
      of 2 months. Outcome measures indicated significant reduction of the patient's
      subjective pain reports and considerable improvement in functional and
      occupational tasks. A follow-up visit at 4 months (2 months after last treatment)
      showed that the improvement was maintained. CONCLUSION: A combined program of
      mobilization with movement and kinesiology tape reduced pain, increased range of
      motion, and increased tip pinch strength in a patient with severe functional
      impairment related to dominant TMC OA.

PMID- 24294152
TI  - Treatment of carpal tunnel syndrome by members of the American Association for
      Hand Surgery.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common compressive
      neuropathy affecting the upper extremity, yet evidence-based guidelines for its
      diagnosis and treatment are lacking. We set out to expose any potential
      discrepancies in CTS practice attitudes based on surgeon's academic background,
      residency training, clinical experience, and other factors. METHODS: This was an
      online survey-based study. Members of the American Association for Hand Surgery
      (AAHS) were sent an electronic mail request (n = 817). The online questionnaire
      consisted of 12 questions that queried surgeons' approaches to the diagnosis as
      well as operative and non-operative management of carpal tunnel syndrome.
      RESULTS: One hundred twenty-three surgeons responded to the survey (15.1 %). The
      locations of surgical practices varied within the United States and beyond. Most
      respondents were either orthopedic or plastic surgeons. With respect to practice
      duration, 15.4 % had been in practice for 5 years or less, 30.9 % of the
      respondents had been in practice between 6 and 15 years, 30.9 % had been in
      practice between 16 and 25 years, and 26.8 % had been in practice for more than
      25 years. The most notable interspecialty differences were related to the use of
      operative antibiotics and the surgical approach. Plastic surgeons were less
      likely to recommend antibiotic use during surgery and more likely to utilize an
      open extensile approach during surgical release. Younger surgeons were more
      likely to employ a mini-open approach for carpal tunnel release. CONCLUSIONS: We
      conclude that background training and generational differences contribute to the
      varied approaches observed in the diagnosis and management of CTS.

PMID- 24294153
TI  - Impairment and disability: Renoir's adaptive coping strategies against rheumatoid
      arthritis.
AB  - Pierre-Auguste Renoir was one of the most influential painters in art history,
      but few people know that he suffered from debilitating rheumatoid arthritis.
      Despite his arthritis, he was able to maintain an incredible level of precision
      and efficiency with his painting. More importantly, he remained positive and did
      not let his condition affect his passion for painting or take away from the
      beauty that he saw in the world around him. Renoir applied a wide variety of
      coping mechanisms and used his ingenuity to come up with different ways to
      continue painting even as his arthritis weakened him. Renoir's long battle with
      rheumatoid arthritis serves as an inspiration to patients who experience the pain
      and limited mobility associated with this disease, encouraging them to persevere
      and to develop coping mechanisms that prevent the effects of their impairment
      from disabling them. 

PMID- 24294154
TI  - Minimally invasive partial fasciectomy for Dupuytren's contractures.
AB  - BACKGROUND: Numerous options exist for the treatment of Dupuytren's contracture.
      This study describes the technique and early results of partial fasciectomy
      through a mini-incision approach as an additional treatment option for
      Dupuytren's disease. METHODS: This procedure involves the excision of diseased
      Dupuytren's tissue with the use of multiple 1 cm transverse incisions. Patient
      demographics, digit involvement, the number of incisions required to release each
      digit, and complications were recorded for all patients. Range of motion data was
      obtained from a subgroup of patients that had at least 6 months of follow-up. A
      paired t test was used to compare preoperative and postoperative contracture.
      RESULTS: Sixty-seven patients underwent 75 procedures that involved 119 digits.
      The mean patient age at the time of surgery was 63 years (range, 33-95 years). A
      total of 32 digits (47 joints) were available for range of motion analysis. After
      a mean of 2.2 years following surgery, metacarpophalangeal joint contractures
      maintained correction (34 degrees  preoperatively, 19 degrees  postoperatively, p
      = 0.008). After a mean postoperative duration of 2.0 years, proximal
      interphalangeal joint contractures trended worse than preoperative levels (39
      degrees  preoperatively, 45 degrees  postoperatively, p = 0.319). There was one
      major complication, which consisted of a nerve laceration that was identified and
      repaired intraoperatively. CONCLUSIONS: Partial fasciectomy through the described
      mini-incision approach provides an additional surgical option for patients who
      desire a less invasive surgical procedure than traditional fascietomy. Although
      this procedure is safe and effective at achieving immediate cord release,
      maintenance of correction for proximal interphalangeal joint contractures remains
      problematic.

PMID- 24294155
TI  - Correlation between preoperative Kimura inching studies and intraoperative
      findings during endoscopic-assisted decompression of the ulnar nerve at the
      elbow.
AB  - BACKGROUND: During the evolution of the senior author's technique of ulnar nerve
      transposition to in situ decompression for ulnar neuropathy at the elbow, nerve
      conduction studies (NCS) including the Kimura inching method were performed
      preoperatively in an effort to ensure that all potential sites of compression
      were investigated intraoperatively. The purpose of this study is to compare the
      results of the Kimura inching technique with the intraoperative findings noted
      during decompression of the ulnar nerve at the elbow. METHODS: The medical
      records of consecutive patients who underwent in situ decompression of their
      ulnar nerves combined with endoscopic examination between March and December of
      2009 were retrospectively reviewed. The site of ulnar nerve compression noted
      using the Kimura inching technique was compared with the intraoperative findings.
      RESULTS: Twelve consecutive patients (four with bilateral symptoms) underwent
      endoscopic ulnar nerve compression in the study period for a total of 16 cases
      analyzed. In 12 cases, the Kimura method localized the site of compression to
      Osborne's bands and/or the aponeurosis of the flexor carpi ulnaris (FCU).
      Intraoperatively, compression was noted at Osborne's bands, the FCU aponeurosis,
      and/or the FCU) muscle proper in all 16 patients. There was partial or full
      correlation between the nerve conduction data and intraoperative findings in
      13/16 cases. CONCLUSIONS: There was good but not perfect agreement between the
      NCS and intraoperative findings, perhaps because transcutaneous NCS are less
      accurate when a nerve is surrounded by muscle. The information obtained in this
      study is valuable when planning surgery to address ulnar nerve compression.

PMID- 24294156
TI  - Cell migration after synovium graft interposition at tendon repair site.
AB  - BACKGROUND: We have recently reported that interpositional synovium grafts from
      tendon sheath have a potential to accelerate tendon healing when implanted at the
      repair site. The purpose of this study was to investigate the effect of
      orientation of the synovium after synovium graft transplantation, by comparing
      the ability of cells from the visceral and parietal surfaces to migrate into the
      tendon in a canine tissue culture model. METHODS: The synovium graft was placed
      within a complete tendon laceration, with either the visceral or parietal surface
      facing the proximal end of the lacerated tendon. The number of migrating cells
      was quantified by a cell migration assay. Qualitative immunohistochemistry and
      confocal laser microscopy were also used at day 10. RESULTS: Many labeled
      synovial cells were observed within the tendon to which the visceral surface of
      the synovium graft was facing. Migrated cells were also observed on the parietal
      side, but there were fewer cells compared to visceral surface cells. Migrating
      cells all expressed alpha-smooth muscle actin. CONCLUSION: We found that graft
      orientation affected cell migration. Whether this finding has clinical
      significance awaits in vivo study.

PMID- 24294157
TI  - Treatment of dorsal perilunate dislocations and fracture-dislocations using a
      standardized protocol.
AB  - BACKGROUND: The aims of this study were to evaluate the associated injuries
      occurring with acute perilunate instability and to assess the clinical and
      radiographic outcomes of perilunate dislocations and fracture-dislocations
      treated with a combined dorsal and volar approach. METHODS: A total of 45
      patients (46 wrist injuries) with perilunate dislocations and fracture
      dislocations were prospectively evaluated. The size of the mid-carpal ligament
      tear, the location of the scapholunate ligament tear, and the presence of
      osteochondral fragments and of the dorsal radiocarpal ligament avulsions were
      recorded at injury. Final clinical and radiographic outcomes were evaluated in 25
      cases (25 wrists) with a minimum of 6 months of follow-up. RESULTS:
      Intraoperative examination of the 46 cases with operative treatment showed the
      volar carpal ligament tear to be present 100 % of the time and to be an average
      length of 3.4 cm. Complete avulsion of the dorsal extrinsic radiocarpal ligaments
      was found in 65.2 % of cases. The scapholunate ligament was torn in 35 cases.
      Osteochondral fragments were found either volarly or dorsally in 74 % of the
      cases. The average flexion-extension arc was 82 degrees , forearm rotation was
      155 degrees , and grip strength averaged 59 % of the uninjured hand. The average
      final scapholunate angle was 55 degrees  and the scapholunate gap was 2.2 mm.
      CONCLUSION: Treatment of perilunate fracture-dislocations with a combined volar
      and dorsal approach results in reasonable and functional clinical results. The
      incidence of associated injuries with these carpal dislocations is high. Although
      the perilunate fracture-dislocations have a slightly better radiologic alignment
      than the dislocation group, the clinical outcome is similar.

PMID- 24294158
TI  - Modification of VY flap to preserve fingertip contour.
AB  - BACKGROUND: VY flap is a reliable treatment for fingertip amputation injuries.
      Insetting the flap to replicate fingertip contour can be challenging with the
      conventional method of using sutures. We propose a modification of inset
      technique with K-wire to simplify contouring during flap inset. METHODS: Seven
      patients underwent VY flap reconstruction with the modified inset technique for
      fingertip defects ranging from 10 * 15 to 20 * 15 mm. The flaps were advanced
      between 6 and 10 mm and inset with K-wires. The donor site is allowed to heal by
      secondary intention. At 6 months, static two-point discrimination, sensitivity,
      and flap appearance were assessed. RESULTS: All flaps healed uneventfully, and
      each patient returned to work between 8 and 10 weeks. Fingertip and nail contour
      were satisfactory in every case. CONCLUSION: This modification simplified
      contouring during flap inset and provided a viable alternative to flap inset and
      contour adjustment.

PMID- 24294159
TI  - A new documentation system for congenital absent digits.
AB  - BACKGROUND: Congenital absent digits continue to be described by many confusing
      terms and are currently classified in categories I, V, and VI of the
      International Federation of Societies for Surgery of the Hand classification and
      seven subclassification systems. Very few classification systems provide any
      logical basis for surgical reconstruction. The purpose of this study was to
      develop a simple alphanumerical documentation system to reproducibly describe the
      morphological or radiographic appearance of congenital absent digits and
      facilitate communication of these childrens' hand anomalies from one hand surgeon
      to another. METHODS: Dorsal and palmar photographs and PA radiographs of 235
      hands in 204 children born with congenital absent digits over a 15-year period
      were analyzed to determine which digital rays were missing and their level of
      absence. Each hand can be described by three letters, R (radial), C (central),
      and U (ulnar), as well as numbers 1-5. The first letter and number designate
      which rays are missing and the second and third letters and numbers designate
      which rays remain present. RESULTS: There are 15 morphological phenotypes of
      congenital absent digits. The three most common phenotypes are U4R1 (a thumb but
      absence of all four fingers), R1U4 (absent thumb), and R5 (aplastic hand).
      CONCLUSIONS: This new documentation system allows hand surgeons to describe the
      simple morphological or radiographic appearance of congenital absent digits;
      incorporates all the previous subclassification systems that have attempted to
      describe congenital absent digits in radial, central, and ulnar deficiencies,
      symbrachydactyly, and congenital constriction ring syndrome; and has subsequently
      allowed the development of an algorithm which predicts whether conventional or
      microsurgical reconstruction is indicated for each specific phenotype.

PMID- 24294161
TI  - Association between individual DASH tasks and restricted wrist flexion and
      extension after volar plate fixation of a fracture of the distal radius.
AB  - BACKGROUND: Symptoms and psychosocial factors are suggested to account for more
      of the variation in disability than physical impairment, but perhaps less so at
      the level of specific tasks. This study assessed the influence of impaired wrist
      motion on specific tasks on the Disabilities of the Arm, Shoulder, and Hand
      (DASH) questionnaire. METHODS: Sixty-three patients with an operatively treated
      fracture of the distal radius completed the Pain Catastrophizing Scale (PCS),
      Pain Anxiety Symptoms Scale, and Center for Epidemiologic Studies Depression
      Scale (CES-D) just before surgery and the DASH questionnaire 3 months after
      surgery. Nine questions on the DASH were selected as potentially sensitive to
      changes in wrist motion and evaluated in bivariate and multivariable analyses.
      RESULTS: In multivariable models of factors associated with specific tasks, only
      "Open a tight or new jar" was affected by wrist flexion and PCS accounting for 33
      % of the variation. Motion, pain, and PCS were significant predictors of the DASH
      score. Among the eight tasks not related to wrist motion, 33 % of the variation
      in disability with writing was accounted for by PCS and limb dominance; 20 % of
      disability preparing a meal by pain, CES-D, and PCS; 14 % of disability with
      making a bed by pain and CES-D; and 23 % of changing a light bulb overhead by
      age, pain, and fracture type. CONCLUSIONS: After volar plate fixation of a
      fracture of the distal radius, upper extremity disability based on select items
      from the DASH questionnaire correlated minimally with impairment of wrist motion,
      even at the level of specific tasks. LEVEL OF EVIDENCE: Prognostic Level II.

PMID- 24294160
TI  - Development of a method for analyzing three-dimensional scapula kinematics.
AB  - BACKGROUND: Scapula mobility complicates upper extremity kinematics assessment.
      Existing methods are diverse, providing inconsistent results. The current gold
      standard (bone pins) is prohibitively invasive. The purposes of the current study
      are to describe a virtual projection alternative to surface markers for video
      motion capture (VMC) of the scapula and to compare the results of the projection
      and surface marker methods to the results of similar existing methods. METHODS:
      Ten participants were evaluated using VMC. Surface markers were applied to the
      trunk and arm in accordance with existing guidelines. Three markers were affixed
      to plastic base on the skin over the acromion process. Other scapular landmarks
      were digitized in a neutral position. These landmarks' locations were defined in
      reference to the acromion cluster and used to generate the projection.
      Humerothoracic, glenohumeral, and scapulothoracic kinematics were evaluated
      during shoulder abduction, flexion, and scaption. Joint angles produced by the
      surface markers and the projection were compared by Bonferroni-adjusted t tests.
      The results were compared to prior findings in the literature. RESULTS: The
      projection resulted in greater scapulothoracic upward rotation, internal
      rotation, and anterior-posterior tilt and less glenohumeral elevation (p < .0055)
      than did surface markers. The virtual scapula produced greater estimates of
      scapular mobility than did surface markers, corresponding to pre-existing results
      from similar methodologies. CONCLUSIONS: The result is a noninvasive measurement
      tool that produces different and superior results than do scapula surface
      markers. Measuring scapula kinematics via VMC without bone pins will facilitate
      future investigations into interactions between upper extremity injury,
      kinematics, and activity performance.

PMID- 24294162
TI  - Anatomic reconstruction of the radioulnar ligament.
AB  - INTRODUCTION: Twenty-five patients (19 males and six females) were included in
      the study based on: chronic symptoms of distal radioulnar joint instability,
      demonstrable instability on examination, MRI evidence of radioulnar ligament
      deficiency, and arthroscopic findings of foveal disruption of the radioulnar
      ligament. MATERIALS AND METHODS: Exclusion criteria were: distal radius malunion,
      congenital malformation of the sigmoid notch, DRUJ arthritis, and less than 24
      months minimum follow-up. Mean age was 35 years old with a mean interval from
      injury to surgery of 5 months. Surgery began with arthroscopic confirmation of
      the chronic foveal detachment followed by open reconstruction of the radioulnar
      ligament using the palmaris longus tendon. The specific method employed three
      drill tunnels corresponding to the true anatomic points of attachment of the
      radioulnar ligament. Patients were examined post-operatively at 2 weeks, 4 weeks,
      6 weeks, 12 weeks, and 6 months. RESULTS AND DISCUSSION: Final evaluation
      averaged 51 (+/-14) months following surgery. Measures obtained before and after
      treatment included: wrist range of motion, forearm range of motion, grip
      strength, examination findings of distal radioulnar joint instability, and
      Disabilities of Arm, Shoulder, and Hand (DASH) scores. Pre-operative and post
      operative measures were compared using the paired Student's t test, accepting a p
      value of 0.05 as statistically significant. All patients healed the
      reconstruction without major complications and demonstrated distal radioulnar
      joint stability at the 6-week examination. Mean ranges of motion, in degrees, pre
      /post-operative were: wrist flexion 53 (+/-13)/61 (+/-10), wrist extension 53 (+/
      13)/62 (+/-15), supination 65 (+/-12)/74 (+/-7), and pronation 66 (+/-11)/71 (+/
      8). Grip strengths expressed as % contralateral pre-/post-operative were: 57 (+/
      23)/79 (+/-25). The differences in these measures were not found to be
      statistically significant. The mean pre-/post-operative DASH scores were: 62 (+/
      16)/7 (+/-3). This difference was found to be statistically significant.
      CONCLUSION: Reconstruction of the RUL with a free palmaris longus tendon graft
      using the truly anatomic points of original RUL attachment at both the ulna and
      radius restored DRUJ stability and improved DASH scores without limiting forearm
      or wrist motion.

PMID- 24294163
TI  - Does the quality, accuracy, and readability of information about lateral
      epicondylitis on the internet vary with the search term used?
AB  - BACKGROUND: Concern exists over the quality, accuracy, and accessibility of
      online information about health care conditions. The goal of this study is to
      evaluate the quality, accuracy, and readability of information available on the
      internet about lateral epicondylitis. METHODS: We used three different search
      terms ("tennis elbow," "lateral epicondylitis," and "elbow pain") in three search
      engines (Google, Bing, and Yahoo) to generate a list of 75 unique websites. Three
      orthopedic surgeons reviewed the content of each website and assessed the quality
      and accuracy of information. We assessed each website's readability using the
      Flesch-Kincaid method. Statistical comparisons were made using ANOVA with post
      hoc pairwise comparisons. RESULTS: The mean reading grade level was 11.1. None of
      the sites were under the recommended sixth grade reading level for the general
      public. Higher quality information was found when using the terms "tennis elbow"
      and "lateral epicondylitis" compared to "elbow pain" (p < 0.001). Specialty
      society websites had higher quality than all other websites (p < 0.001). The
      information was more accurate if the website was authored by a health care
      provider when compared to non-health care providers (p = 0.003). Websites seeking
      commercial gain and those found after the first five search results had lower
      quality information. CONCLUSIONS: Reliable information about lateral
      epicondylitis is available online, especially from specialty societies. However,
      the quality and accuracy of information vary significantly with the search term,
      website author, and order of search results. This leaves less educated patients
      at a disadvantage, particularly because the information we encountered is above
      the reading level recommended for the general public.

PMID- 24294164
TI  - Incidence of metacarpal fractures in the US population.
AB  - BACKGROUND: There are scarce data regarding the epidemiology of metacarpal
      fractures within the US population. The purpose of this study is to report the
      epidemiology of metacarpal fractures in the USA using the National Electronic
      Injury Surveillance System Database (NEISS). METHODS: The NEISS database
      represents a national probability sample of approximately 100 hospitals in the
      USA and its territories. The database was queried for metacarpal fractures during
      the time period 2002-2006. US census data were used to calculate incidence rate
      (IR) for various demographic criteria. RESULTS: A total of 4,718 metacarpal
      fractures were identified, representing approximately 160,790 metacarpal
      fractures. The calculated IR was 13.6 (95 % CI, 13.6-13.67) per 100,000 person
      years. The highest IR occurred in the 10-19 age group (IR 38.8; 95 % CI, 38.6
      38.9) followed by those 20-29 years of age (IR 28.4; 95 % CI, 28.3-28.5).
      Metacarpal fractures were found more commonly in males (IR 23; 95 % CI, 22.9
      23.1) than females (IR 4.5; 95 % CI, 4.5-4.5), with an incidence rate ratio of
      5.08. The most common mechanisms of injury were contact with a wall or door, and
      falls. The most common setting was in the home, followed by recreational
      locations. CONCLUSIONS: The estimated incidence of metacarpal fractures
      presenting for acute hospital care in the USA is 13.6 per 100,000 person-years.
      Males in the second and third decades of life sustain this injury most commonly.
      Metacarpal fractures occur frequently in the home or recreational setting, with
      contact force as the primary mechanism of injury.

PMID- 24294165
TI  - Locking of the metacarpophalangeal joint caused by idiopathic intrinsic muscle
      atrophy of the hand: report of three cases.

PMID- 24294166
TI  - Late presentation of isolated digital contracture following forearm fracture.

PMID- 24294167
TI  - Carpal tunnel syndrome caused by a large osteochondroma.

PMID- 24294168
TI  - Pediatric blastomycotic osteomyelitis of the hand.

PMID- 24294169
TI  - Evaluation of patients' perception of safety to drive after outpatient, minimally
      invasive procedures of the hand.

PMID- 24294170
TI  - Locking of the index finger metacarpophalangeal joint due to a chronic
      osteochondral fracture fragment of the metacarpal head: a case report.

PMID- 24294171
TI  - Unusual proximal dislocation without fracture: a case report.
AB  - Carpal instability includes a broad spectrum of osseous and ligamentous injuries
      which have been subclassified into greater and lesser arc injuries, in addition
      to combinations of both (Mayfield et al. J Hand Surg [Am] 5:226-241, 1980; Yaeger
      et al. Skeletal Radiol 13(2):120-30, 1985). The injuries typically occur from a
      fall on the outstretched hand with the wrist in ulnar deviation, hyperextension,
      and intercarpal supination (Yaeger et al. Skeletal Radiol 13(2):120-30, 1985).
      The force classically propagates from the radial to the ulnar side of the wrist
      resulting in a fracture (greater arc) or dislocation (lesser arc) pattern with
      the extent of the injury occurring in an orderly pattern depending upon the
      degree of hyperextension and the duration and magnitude of the force (Mayfield et
      al. J Hand Surg [Am] 5:226-241, 1980; Yaeger et al. Skeletal Radiol 13(2):120-30,
      1985). Multiple variations occur, including transradial styloid fractures as well
      as fractures through carpal bones surrounding the lunate (Mayfield et al. J Hand
      Surg [Am] 5:226-241, 1980; Yaeger et al. Skeletal Radiol 13(2):120-30, 1985;
      Kozin SH. J Am Acad Orthop Surg 6 (2): 114-20, 1998. Although carpal dislocations
      have been noted for many years, the mechanisms and classification have only been
      recently clarified. We report a case of a complex dislocation involving the
      entire proximal carpal row without an associated fracture. While this type of
      complex carpal dislocation has been previously described, to our knowledge, it
      has never been reported without a fracture of the forearm, wrist, or hand. 

PMID- 24294172
TI  - Corticocancellous olecranon autograft for metacarpal defect reconstruction: a
      case report.
AB  - BACKGROUND: High-energy injuries to the hand frequently lead to bone defects as
      well as soft tissue loss. Early bone grafting of defects is well established in
      the literature; however, few options are available for autologous
      corticocancellous grafts. Most frequently cited studies describe the iliac crest
      or the distal radius donor sites. METHODS: In this case report, we describe a new
      technique of obtaining corticocancellous bone graft from the olecranon. RESULTS:
      Complete union of the segmental defect was achieved with this technique.
      CONCLUSIONS: The olecranon donor site is outside the zone of injury and therefore
      safe to access, but within the upper extremity, thus avoiding the need for
      harvest from a distant site such as the iliac crest or the distal femur.
      Additional benefits of this site are the greater volume of graft that can be
      harvested compared to the distal radius as well as a more optimal ratio of
      cancellous to cortical graft available, compared to the iliac crest where the
      graft may be excessively cortical in nature.

PMID- 24294173
TI  - A three-step technique to correctly identify the trapezium without the need for
      fluoroscopic imaging.
AB  - Thumb pain secondary to degenerative arthritis of the carpometacarpal joint of
      the thumb is a common disabling condition. The key principles of successful basal
      joint arthroplasty involve trapezial excision, which is required for pain relief,
      with or without some form of ligament reconstruction. The majority of basal joint
      reconstructive procedures include partial or complete trapeziectomy, with and
      without some types of tendon transfer and ligament reconstruction and with or
      without tendon interposition and/or temporary wire stabilisation. When performing
      a trapeziectomy, it is important to identify the trapezium correctly before
      excising it. Excision of the incorrect bone during trapeziectomy for basal joint
      arthritis of the thumb has been reported within the NHS Litigation Authority
      database. We describe the senior author's routinely used three-step technique to
      confirm the identity of the trapezium before excision. This technique has been
      reliably used in over 300 cases with successful excision of the trapezium without
      intraoperative fluoroscopy. 

PMID- 24294174
TI  - Polydactyly in the Southwest: art or anatomy-a photo essay.
AB  - Rock art in the Four Corners area often includes pictures of hands and feet,
      which may be representational or symbolic. There is correlation between actual
      metatarsal bones and carvings of polydactyl feet. No duplicated hand bones have
      been found, but we postulate petroglyphs of polydactyl hands are a reflection of
      a real congenital difference. 

PMID- 24294175
TI  - MicroRNAs and long non-coding RNAs: prospects in diagnostics and therapy of
      cancer.
AB  - BACKGROUND: Non-coding RNAs (ncRNAs) are key regulatory molecules in cellular
      processes, and are potential biomarkers in many diseases. Currently, microRNAs
      and long non-coding RNAs are being pursued as diagnostic and prognostic
      biomarkers, and as therapeutic tools in cancer, since their expression profiling
      is able to distinguish different cancer types and classify their sub-types.
      CONCLUSIONS: There are numerous studies confirming involvement of ncRNAs in
      cancer initiation, development and progression, but have only been recently
      identified as new diagnostic and prognostic tools. This can be beneficial in
      future medical cancer treatment options, since ncRNAs are natural antisense
      interactors included in regulation of many genes connected to survival and
      proliferation. Research is directed in development of useful markers for
      diagnosis and prognosis in cancer and in developing new RNA-based cancer
      therapies, of which some are already in clinical trials.

PMID- 24294177
TI  - Expansive growth of two glioblastoma stem-like cell lines is mediated by bFGF and
      not by EGF.
AB  - BACKGROUND: Patient-derived glioblastoma (GBM) stem-like cells (GSCs) represent a
      valuable model for basic and therapeutic research. GSCs are usually propagated in
      serum-free Neural Basal medium supplemented with bFGF and EGF. Yet, the exact
      influence of these growth factors on GSCs is still unclear. Recently it was
      suggested that GBM stem-like cells with amplified EGFR should be cultured in stem
      cell medium without EGF, as the presence of EGF induced rapid loss of EGFR
      amplification. However, patient biopsies are usually taken into culture before
      their genomic profiles are defined. Thus, an important question remains whether
      GBM cells without EGFR amplification also can be cultured in stem cell medium
      without EGF. MATERIALS AND METHODS: [corrected] To address this question, we used
      two heterogeneous glioblastoma GSC lines (NCH421k and NCH644) that lack EGFR
      amplification. RESULTS: Although both cell lines showed very low EGFR expression
      under standard growth conditions, bFGF stimulation induced higher expression of
      EGFR in NCH644. In both cell lines, expression of the stem cell markers nestin
      and CD133 was higher upon stimulation with bFGF compared to EGF. Importantly,
      bFGF stimulated the growth of both cell lines, whereas EGF had no effect. We
      verified that the growth stimulation by bFGF was either mediated by proliferation
      (NCH421k) or resistance to apoptosis (NCH644). CONCLUSIONS: We demonstrate that
      GSC cultures without EGFR amplification can be maintained and expanded with bFGF,
      while the addition of EGF has no significant effect and therefore can be omitted.

PMID- 24294176
TI  - Emerging clinical importance of the cancer biomarkers kallikrein-related
      peptidases (KLK) in female and male reproductive organ malignancies.
AB  - BACKGROUND: Tumor tissue-associated KLKs (kallikrein-related peptidases) are
      clinically important biomarkers that may allow prognosis of the cancer disease
      and/or prediction of response/failure of cancer patients to cancer-directed
      drugs. Regarding the female/male reproductive tract, remarkably, all of the
      fifteen KLKs are expressed in the normal prostate, breast, cervix uteri, and the
      testis, whereas the uterus/endometrium and the ovary are expressing a limited
      number of KLKs only. CONCLUSIONS: Most of the information regarding elevated
      expression of KLKs in tumor-affected organs is available for ovarian cancer;
      depicting them as valuable biomarkers in the cancerous phenotype. In contrast,
      for breast cancer, a series of KLKs was found to be downregulated. However, in
      breast cancer, KLK4 is elevated which is also true for ovarian and prostate
      cancer. In such cases, selective synthetic KLK inhibitors that aim at blocking
      the proteolytic activities of certain KLKs may serve as future candidate
      therapeutic drugs to interfere with tumor progression and metastasis.

PMID- 24294178
TI  - Heterogeneity of uroplakin localization in human normal urothelium, papilloma and
      papillary carcinoma.
AB  - BACKGROUND: Uroplakins are differentiation-related membrane proteins of
      urothelium. We compared uroplakin expression and ultrastructural localization in
      human normal urothelium, papilloma and papillary carcinoma. Because of high
      recurrence rate of these tumours, treated by transurethral resection, we
      investigated urothelial tumour, resection border and uninvolved urothelium.
      PATIENTS AND METHODS: Urinary bladder samples were obtained from tumour free
      control subjects and patients with papilloma and papillary carcinoma.
      Immunohistochemical and immunoelectron labelling of uroplakins were performed.
      RESULTS: In normal human urothelium with continuous uroplakin-positive
      superficial cell layer uroplakins were localized to flattened mature fusiform
      vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin
      expression was found in papilloma and papillary carcinoma. Three aberrant
      differentiation stages of urothelial cells, not found in normal urothelium, were
      recognized in tumours. Diverse uroplakin expression and aberrant differentiation
      were occasionally found in resection border and in uninvolved urothelium.
      CONCLUSIONS: We demonstrated here that uroplakin expression and localization in
      urothelial tumours is altered when compared to normal urothelium. In patients
      with papilloma and papillary carcinoma immunolabelling of uroplakins at
      ultrastructural level shows aberrant urothelial differentiation. It is possible
      that aberrant differentiation stages of urothelial cells in resection border and
      in uninvolved urothelium contribute to high recurrence rate.

PMID- 24294179
TI  - Biological evaluation of transdichloridoplatinum(II) complexes with 3- and 4
      acetylpyridine in comparison to cisplatin.
AB  - BACKGROUND: In our previous study we reported the synthesis and cytotoxicity of
      two trans-platinum(II) complexes: trans-[PtCl2(3-acetylpyridine)2] (1) and trans
      [PtCl2(4-acetylpyridine)2] (2), revealing significant cytotoxic potential of 2.
      In order to evaluate the mechanism underlying biological activity of both trans
      Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC
      5 and MS1 cells. MATERIALS AND METHODS: The cytotoxic activity of the
      investigated complexes was determined using SRB assay. The colagenolytic activity
      was determined using gelatin zymography, while the effect of platinum complexes
      on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by
      quantitative real-time PCR. Apoptotic potential and cell cycle alterations were
      determined by FACS analyses. Western blot analysis was used to evaluate the
      effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR
      was used for the ERCC1 mRNA expression analysis. In vitro antiangiogenic
      potential was determined by tube formation assay. Platinum content in
      intracellular DNA and proteins was determined by inductively coupled plasma
      optical emission spectrometry. RESULTS: Compound 2 displayed an apparent
      cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2
      exerted antiproliferative effect through apoptosis induction, while 1 induced
      both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real
      time PCR and Western blot, was associated with down-regulation of ERCC1. Both
      trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly
      abrogated in vitro tubulogenesis in MS1 cells. CONCLUSIONS: The ability of 2 to
      induce multiple and selective in vitro cytotoxic effects encourages further
      investigations of trans-platinum(II) complexes with substituted pyridines.

PMID- 24294180
TI  - Dual time point imaging fluorine-18 flourodeoxyglucose positron emission
      tomography for evaluation of large loco-regional recurrences of breast cancer
      treated with electrochemotherapy.
AB  - BACKGROUND: Electrochemotherapy is a local anticancer treatment very efficient
      for treatment of small cutaneous metastases. The method is now being investigated
      for large cutaneous recurrences of breast cancer that are often confluent masses
      of malignant tumour with various degrees of inflammation. To this end 18-Flourine
      Flourodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT)
      could be a method for response evaluation. However, a standard FDG-PET/CT scan
      cannot differentiate inflammatory tissue from malignant tissue. Dual point time
      imaging (DTPI) FDG-PET has the potential of doing so. The purpose of this study
      was to investigate if DTPI FDG-PET/CT could assess response to
      electrochemotherapy and to assess the optimal timing of imaging. PATIENTS AND
      METHODS: Within a phase II clinical trial 11 patients with cutaneous recurrences
      had FDG-PET/CT scans at three time points: 60 min, 120 min and 180 min after FDG
      injection. The scans were performed before and 3 weeks after electrochemotherapy.
      RESULTS: A significant reduction in maximum standard uptake value at 60 min post
      injection was seen after treatment. Furthermore a change in the FDG uptake
      pattern was observed; from increasing uptake in up to 180 min post injection
      before treatment to stabilization of FDG uptake at 120 min post injection after
      treatment. The change in FDG uptake pattern over time lead to change of response
      in three target lesions; two lesions changed from stable metabolic disease to
      partial metabolic response and one lesion changed from partial metabolic response
      to stable metabolic disease. To ensure detection of the change in uptake pattern,
      scanning 60 and 180 min post injection seems optimal. CONCLUSIONS: The present
      study shows that FDG-PET/CT 60 and 180 min after tracer injection is a promising
      tool for response evaluation of cutaneous recurrences of breast cancer treated
      with electrochemotherapy.

PMID- 24294181
TI  - Electrochemotherapy as a new therapeutic strategy in advanced Merkel cell
      carcinoma of head and neck region.
AB  - BACKGROUND: Merkel Cell Carcinoma (MCC) is a rare and aggressive tumour, arising
      from a cutaneous mechanoceptor cell located in the basal layer of epidermis, with
      poor prognosis. The treatment of choice for the initial stage of the disease is
      surgery and/or radiotherapy. The treatment of recurrent or advanced disease is
      still controversial. CASE REPORT: We report a case of 84 years old woman with a
      recurrent MCC of the chin treated with electrochemotherapy (ECT). During the
      period of 20 months, four sessions of ECT were employed, which resulted in an
      objective response of the tumour and good quality of residual life. CONCLUSIONS:
      Our case shows the effectiveness of ECT in the treatment of locally advanced MCC
      of the head and neck region in a patient not suitable for standard therapeutic
      options.

PMID- 24294182
TI  - Minimally invasive treatment of peristomal metastases from gastric cancer at an
      ileostomy site by electrochemotherapy.
AB  - BACKGROUND: Peristomal metastases are rare, but potentially associated with
      relevant morbidity. Surgical resection, followed by stoma relocation, represent
      the gold standard in most patients. We describe electrochemotherapy (ECT), a
      minimally invasive method for locally-enhancing drug delivery by means of
      electric pulses, as an alternative approach. PATIENT AND METHODS: A 49-year-old
      man with advanced gastric cancer developed skin metastases around an ileostomy
      site. The ulcerated and oozing tumor growth impaired patient's quality of life
      due to continuous trouble in fitting the ostomy appliance, its poor adherence and
      consequent stools spillage. ECT consisted of a 20-minute course under mild
      general sedation. A bleomycin bolus of 15 000 IU/m(2) was followed by the
      percutaneous application of multiple, 1.5 ms -long electric pulses by means of a
      needle electrode. RESULTS: Post ECT course was uneventful and the patient was
      discharged on the same day. After one week, tumor nodules were flattened and
      partial tumor regression was appreciable at one-month follow-up. More
      importantly, peristomal skin conditions significantly improved, thus allowing for
      an effective application of the ostomy appliance during the following moths,
      until patient's death. CONCLUSIONS: This report suggests the feasibility of ECT
      as a minimally invasive approach for peristomal tumors. In selected cases, ECT,
      by achieving a rapid tumor control, may ensure effective ostomy management and
      preserve patients' quality of life.

PMID- 24294183
TI  - Effect of ionizing radiation on human skeletal muscle precursor cells.
AB  - BACKGROUND: Long term effects of different doses of ionizing radiation on human
      skeletal muscle myoblast proliferation, cytokine signalling and stress response
      capacity were studied in primary cell cultures. MATERIALS AND METHODS: Human
      skeletal muscle myoblasts obtained from muscle biopsies were cultured and
      irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects
      of radiation were studied by interleukin - 6 (IL-6) release and stress response
      detected by the heat shock protein (HSP) level, while long term effects were
      followed by proliferation capacity and cell death. RESULTS: Compared with non
      irradiated control and cells treated with inhibitor of cell proliferation Ara C,
      myoblast proliferation decreased 72 h post-irradiation, this effect was more
      pronounced with increasing doses. Post-irradiation myoblast survival determined
      by measurement of released LDH enzyme activity revealed increased activity after
      exposure to irradiation. The acute response of myoblasts to lower doses of
      irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher
      doses of irradiation triggered a stress response in myoblasts, determined by
      increased levels of stress markers (HSPs 27 and 70). CONCLUSIONS: Our results
      show that myoblasts are sensitive to irradiation in terms of their proliferation
      capacity and capacity to secret IL-6. Since myoblast proliferation and
      differentiation are a key stage in muscle regeneration, this effect of
      irradiation needs to be taken in account, particularly in certain clinical
      conditions.

PMID- 24294184
TI  - Recombinant human erythropoietin alters gene expression and stimulates
      proliferation of MCF-7 breast cancer cells.
AB  - BACKGROUND: Functional erythropoietin (EPO) signaling is not specific only to
      erythroid lineages and has been confirmed in several solid tumors, including
      breast. Three different isoforms of erythropoietin receptor (EPOR) have been
      reported, the soluble (EPOR-S) and truncated (EPOR-T) forms acting
      antagonistically to the functional EPOR. In this study, we investigated the
      effect of human recombinant erythropoietin (rHuEPO) on cell proliferation, early
      gene response and the expression of EPOR isoforms in the MCF-7 breast cancer cell
      line. MATERIALS AND METHODS: The MCF-7 cells were cultured with or without rHuEPO
      for 72 h or 10 weeks and assessed for their growth characteristics, expression of
      early response genes and different EPOR isoforms. The expression profile of EPOR
      and EPOR-T was determined in a range of breast cancer cell lines and compared
      with their invasive properties. RESULTS: MCF-7 cell proliferation after rHuEPO
      treatment was dependent on the time of treatment and the concentration used. High
      rHuEPO concentrations (40 U/ml) stimulated cell proliferation independently of a
      preceding long-term exposure of MCF-7 cells to rHuEPO, while lower concentrations
      increased MCF-7 proliferation only after 10 weeks of treatment. Gene expression
      analysis showed activation of EGR1 and FOS, confirming the functionality of EPOR.
      rHuEPO treatment also slightly increased the expression of the functional EPOR
      isoform, which, however, persisted throughout the 10 weeks of treatment. The
      expression levels of EPOR-T were not influenced. There were no correlations
      between EPOR expression and the invasiveness of MCF-7, MDA-MB-231, Hs578T,
      Hs578Bst, SKBR3, T-47D and MCF-10A cell lines. CONCLUSIONS: rHuEPO modulates MCF
      7 cell proliferation in time- and concentration-dependent manner. We confirmed
      EGR1, FOS and EPOR as transcription targets of the EPO-EPOR signaling loop, but
      could not correlate the expression of different EPOR isoforms with the
      invasiveness of breast cancer cell lines.

PMID- 24294185
TI  - The usefulness of F-18 FDG PET/CT-mammography for preoperative staging of breast
      cancer: comparison with conventional PET/CT and MR-mammography.
AB  - BACKGROUND: The objective of the study was to compare the diagnostic efficacy of
      an integrated Fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT-mammography (mammo
      PET/CT) with conventional torso PET/CT (supine-PET/CT) and MR-mammography for
      initial assessment of breast cancer patients. PATIENTS AND METHODS: Forty women
      (52.0 +/- 12.0 years) with breast cancer who underwent supine-PET/CT, mammo
      PET/CT, and MR-mammography from April 2009 to August 2009 were enrolled in the
      study. We compared the size of the tumour, tumour to chest wall distance, tumour
      to skin distance, volume of axillary fossa, and number of meta-static axillary
      lymph nodes between supine-PET/CT and mammo-PET/CT. Next, we assessed the
      difference of focality of primary breast tumour and tumour size in mammo-PET/CT
      and MR-mammography. Histopathologic findings served as the standard of reference.
      RESULTS: In the comparison between supine-PET/CT and mammo-PET/CT, significant
      differences were found in the tumour size (supine-PET/CT: 1.3 +/- 0.6 cm, mammo
      PET/CT: 1.5 +/- 0.6 cm, p < 0.001), tumour to thoracic wall distance (1.8 +/- 0.9
      cm, 2.2 +/- 2.1 cm, p < 0.001), and tumour to skin distance (1.5 +/- 0.8 cm, 2.1
      +/- 1.4 cm, p < 0.001). The volume of axillary fossa was significantly wider in
      mammo-PET/CT than supine-PET/CT (21.7 +/- 8.7 cm(3) vs. 23.4 +/- 10.4 cm(3), p =
      0.03). Mammo-PET/CT provided more correct definition of the T-stage of the
      primary tumour than did supine-PET/CT (72.5% vs. 67.5%). No significant
      difference was found in the number of metastatic axillary lymph nodes. Compared
      with MR-mammography, mammo-PET/CT provided more correct classification of the
      focality of lesion than did MR-mammography (95% vs. 90%). In the T-stage, 72.5%
      of cases with mammo-PET/CT and 70% of cases with MR-mammography showed
      correspondence with pathologic results. CONCLUSIONS: Mammo-PET/CT provided more
      correct definition of the T-stage and evaluation of axillary fossa may also be
      delineated more clearly than with supine-PET/CT. The initial assessment of mammo
      PET/CT would be more useful than MR-mammography because the mammo-PET/CT
      indicates similar accuracy with MR-mammography for decision of T-stage of primary
      breast tumour and more correct than MR-mammography for defining focality of
      lesion.

PMID- 24294186
TI  - Role of contrast-enhanced ultrasound in evaluating the efficiency of ultrasound
      guided percutaneous microwave ablation in patients with renal cell carcinoma.
AB  - BACKGROUND: The aim of the study was to evaluate the efficiency and feasibility
      of contrast-enhanced ultrasound (CEUS) with Sonovue in assessing of renal cell
      carcinomas (RCCs) following ultrasound (US)-guided percutaneous microwave
      ablation (MWA). PATINETS AND METHODS: Seventy-nine patients (60 males and 19
      females) with 83 lesions (mean size 3.2+/-1.6 cm) were treated by US-guided
      percutaneous MWA. The CEUS results of the third day after the ablation were
      compared with the synchronous contrast-enhanced computed tomography (CT)/magnetic
      resonance imaging (MRI) results and biopsy pathological results. The follow-up
      was performed by CEUS and CT/MRI after 1, 3, 6 months and every 6 months
      subsequently. The combination of clinical follow-up results and CT/MRI imaging
      findings was the reference standard of CEUS results for evaluating the
      therapeutic effect. The identification of residual or recurrence tumour was
      assessed by two blinded radiologists. RESULTS: On the third day after MWA, CEUS
      showed 68 of 83 lesions (68/83, 81.9%) successfully ablated and 15 of 83 (18.1%)
      with residual tumours. Among residual tumours, 13 (86.7%) were confirmed by
      contrast-enhanced CT/MRI findings and biopsy results. The sensitivity,
      specificity, accuracy, positive and negative predictive value of CEUS evaluating
      the short-term MWA effectiveness were 100%, 97.1%, 97.6%, 86.7% and 100%,
      respectively. During the six years follow-up (median 26 months), the CEUS showed
      recurrence in 7 patients, and six of them achieved consistent results on CEUS and
      CT/MRI imaging. The sensitivity, specificity, accuracy, positive and negative
      predictive value for CEUS evaluating long-term MWA effectiveness were 85.7%,
      98.7%, 97.6%, 85.7% and 98.7%, respectively. CONCLUSIONS: The post-procedural
      CEUS demonstrated as an effective and feasible method in evaluating a therapeutic
      effect of RCCs following MWA.

PMID- 24294187
TI  - Impact of CD133 positive stem cell proportion on survival in patients with
      glioblastoma multiforme.
AB  - BACKGROUND: The aim of the study was to assess the impact of CD133-positive
      (CD133+) cancer stem cell proportions on treatment results of glioblastoma
      multiforme (GBM) patients. PATIENTS AND METHODS: Patients with GBM (n = 42)
      received postoperative radiotherapy (+/- chemotherapy). Surgically excised GBM
      tissue sections were immunohistochemically examined for CD133 expression. The
      proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM
      stem cells was established by 2 independent researchers whose results were in
      good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were
      correlated with patients overall survival. RESULTS: The proportion of CD133+
      cells varied between patients, being from 0.5% to 82%. Mean and median
      proportions of CD133+ cells of the entire study group were 33% +/- 24% (mean +/-
      SD) and 28%, respectively. Clinical data do not support the association between
      higher proportion of stem cells and the aggressiveness of GBM. Median survival
      time of the study group was 10.0 months (95% CI 9.0-11.0). The survival time
      clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02).
      Median survival times for patients with low (< median) and high (>= median)
      proportion of CD133+ cells were 9.0 months (95% CI 7.6-10.5) and 12.0 months (95%
      CI 9.3-14.7), respectively. In multivariate analysis, the proportion of CD133+
      cells emerged as a significant independent predictor for longer overall survival
      (HR 2.0, 95% CI 1.0-3.8, p = 0.04). CONCLUSIONS: In patients with higher stem
      cell proportion, significantly longer survival times after postoperative
      radiotherapy were achieved. Underlying reasons and possible higher sensitivity of
      GBM stem cells to fractionated radio-therapy should be clarified in further
      studies.

PMID- 24294188
TI  - Dosimetric evaluation of an ipsilateral intensity modulated radiotherapy beam
      arrangement for parotid malignancies.
AB  - BACKGROUND: We conducted a dosimetric comparison of an ipsilateral beam
      arrangement for intensity modulated radiotherapy (IMRT) with off-axis beams.
      PATIENTS AND METHODS: Six patients who received post-operative radiotherapy (RT)
      for parotid malignancies were used in this dosimetric study. Four treatment plans
      were created for each CT data set (24 plans): 1) ipsilateral 4-field off-axis
      IMRT (4fld-OA), 2) conventional wedge pair (WP), 3) 7 field co-planar IMRT
      (7fld), and 4) ipsilateral co-planar 4-field quartet IMRT (4fld-CP). Dose, volume
      statistics for the planning target volumes (PTVs) and planning risk volumes
      (PRVs) were compared for the four treatment techniques. RESULTS: Wedge pair plans
      inadequately covered the deep aspect of the PTV. The 7-field IMRT plans delivered
      the largest low dose volumes to normal tissues. Mean dose to the contralateral
      parotid was highest for 7 field IMRT. Mean dose to the contralateral
      submandibular gland was highest for 7 field IMRT and WP. 7 field IMRT plans had
      the highest dose to the oral cavity. The mean doses to the brainstem, spinal
      cord, ipsilateral temporal lobe, cerrebellum and ipsilateral cochlea were similar
      among the four techniques. CONCLUSIONS: For postoperative treatment of the
      parotid bed, 4-field ipsilateral IMRT techniques provided excellent coverage
      while maximally sparing the contralateral parotid gland and submandibular gland.

PMID- 24294189
TI  - Low metabolic activity of biofilm formed by Enterococcus faecalis isolated from
      healthy humans and wild mallards (Anas platyrhynchos).
AB  - It is widely known that Enterococcus faecalis virulence is related to its biofilm
      formation. Although Enterococci are common commensal organisms of the
      gastrointestinal tract, the difference between commensal and pathogen strains
      remain unclear. In this study, we compare the biochemical profile of the biofilms
      formed by two groups of medical and two groups of commensal strains. The medical
      strains were isolated as pathogens from infections of urinary tract and other
      infections (wounds, pus and bedsores), and the commensal strains were taken from
      faeces of healthy volunteers and faeces of wild mallards (Anas platyrhynchos)
      living in an urban environment. The properties of biofilms formed by medical and
      commensal strains differed significantly. Commensal strains showed lower
      metabolic activity and glucose uptake and higher biofilm biomass than the medical
      ones. Consistent with glucose uptake experiments, we found that the glucose
      dehydrogenase gene was more expressed in medical strains. These results indicate
      that higher metabolic activity and lower protein concentration of E. faecalis
      cells within biofilms are formed during infections.

PMID- 24294190
TI  - Modulation of feedback-related negativity during trial-and-error exploration and
      encoding of behavioral shifts.
AB  - The feedback-related negativity (FRN) is a mid-frontal event-related potential
      (ERP) recorded in various cognitive tasks and associated with the onset of
      sensory feedback signaling decision outcome. Some properties of the FRN are still
      debated, notably its sensitivity to positive and negative reward prediction error
      (RPE)-i.e., the discrepancy between the expectation and the actual occurrence of
      a particular feedback,-and its role in triggering the post-feedback adjustment.
      In the present study we tested whether the FRN is modulated by both positive and
      negative RPE. We also tested whether an instruction cue indicating the need for
      behavioral adjustment elicited the FRN. We asked 12 human subjects to perform a
      problem-solving task where they had to search by trial and error which of five
      visual targets, presented on a screen, was associated with a correct feedback.
      After exploration and discovery of the correct target, subjects could repeat
      their correct choice until the onset of a visual signal to change (SC) indicative
      of a new search. Analyses showed that the FRN was modulated by both negative and
      positive prediction error (RPE). Finally, we found that the SC elicited an FRN
      like potential on the frontal midline electrodes that was not modulated by the
      probability of that event. Collectively, these results suggest the FRN may
      reflect a mechanism that evaluates any event (outcome, instruction cue) signaling
      the need to engage adaptive actions. 

PMID- 24294191
TI  - Dynamics of action potential firing in electrically connected striatal fast
      spiking interneurons.
AB  - Fast-spiking interneurons (FSIs) play a central role in organizing the output of
      striatal neural circuits, yet functional interactions between these cells are
      still largely unknown. Here we investigated the interplay of action potential
      (AP) firing between electrically connected pairs of identified FSIs in mouse
      striatal slices. In addition to a loose coordination of firing activity mediated
      by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent
      inhibition of spike discharge in coupled cells. At relatively low firing rates (2
      20 Hz), some APs were tightly synchronized whereas others were inhibited.
      However, burst firing at intermediate frequencies (25-60 Hz) mostly induced spike
      inhibition, while at frequencies >50-60 Hz FSI pairs tended to synchronize. Spike
      silencing occurred even in the absence of GABAergic synapses or persisted after a
      complete block of GABAA receptors. Pharmacological suppression of presynaptic
      spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more
      prone to trigger spikes at near-threshold potentials, leading to a mostly
      synchronous firing activity. The complex pattern of functional coordination
      mediated by GJ endows FSIs with peculiar dynamic properties that may be critical
      in controlling striatal-dependent behavior. 

PMID- 24294193
TI  - Musical expertise and foreign speech perception.
AB  - The aim of this experiment was to investigate the influence of musical expertise
      on the automatic perception of foreign syllables and harmonic sounds.
      Participants were Cuban students with high level of expertise in music or in
      visual arts and with the same level of general education and socio-economic
      background. We used a multi-feature Mismatch Negativity (MMN) design with
      sequences of either syllables in Mandarin Chinese or harmonic sounds, both
      comprising deviants in pitch contour, duration and Voice Onset Time (VOT) or
      equivalent that were either far from (Large deviants) or close to (Small
      deviants) the standard. For both Mandarin syllables and harmonic sounds, results
      were clear-cut in showing larger MMNs to pitch contour deviants in musicians than
      in visual artists. Results were less clear for duration and VOT deviants,
      possibly because of the specific characteristics of the stimuli. Results are
      interpreted as reflecting similar processing of pitch contour in speech and non
      speech sounds. The implications of these results for understanding the influence
      of intense musical training from childhood to adulthood and of genetic
      predispositions for music on foreign language perception are discussed. 

PMID- 24294192
TI  - New roles for the cerebellum in health and disease.
AB  - The cerebellum has a well-established role in maintaining motor coordination and
      studies of cerebellar learning suggest that it does this by recognizing neural
      patterns, which it uses to predict optimal movements. Serious damage to the
      cerebellum impairs this learning and results in a set of motor disturbances
      called ataxia. However, recent work implicates the cerebellum in cognition and
      emotion, and it has been argued that cerebellar dysfunction contributes to non
      motor conditions such as autism spectrum disorders (ASD). Based on human and
      animal model studies, two major questions arise. Does the cerebellum contribute
      to non-motor as well as motor diseases, and if so, how does altering its function
      contribute to such diverse symptoms? The architecture and connectivity of
      cerebellar circuits may hold the answers to these questions. An emerging view is
      that cerebellar defects can trigger motor and non-motor neurological conditions
      by globally influencing brain function. Furthermore, during development
      cerebellar circuits may play a role in wiring events necessary for higher
      cognitive functions such as social behavior and language. We discuss genetic,
      electrophysiological, and behavioral evidence that implicates Purkinje cell
      dysfunction as a major culprit in several diseases and offer a hypothesis as to
      how canonical cerebellar functions might be at fault in non-motor as well as
      motor diseases. 

PMID- 24294194
TI  - A neurobiology of learning beyond the declarative non-declarative distinction.

PMID- 24294195
TI  - Multisensory integration of dynamic emotional faces and voices: method for
      simultaneous EEG-fMRI measurements.
AB  - Combined EEG-fMRI analysis correlates time courses from single electrodes or
      independent EEG components with the hemodynamic response. Implementing
      information from only one electrode, however, may miss relevant information from
      complex electrophysiological networks. Component based analysis, in turn, depends
      on a priori knowledge of the signal topography. Complex designs such as studies
      on multisensory integration of emotions investigate subtle differences in
      distributed networks based on only a few trials per condition. Thus, they require
      a sensitive and comprehensive approach which does not rely on a-priori knowledge
      about the underlying neural processes. In this pilot study, feasibility and
      sensitivity of source localization-driven analysis for EEG-fMRI was tested using
      a multisensory integration paradigm. Dynamic audiovisual stimuli consisting of
      emotional talking faces and pseudowords with emotional prosody were rated in a
      delayed response task. The trials comprised affectively congruent and incongruent
      displays. In addition to event-locked EEG and fMRI analyses, induced oscillatory
      EEG responses at estimated cortical sources and in specific temporo-spectral
      windows were correlated with the corresponding BOLD responses. EEG analysis
      showed high data quality with less than 10% trial rejection. In an early time
      window, alpha oscillations were suppressed in bilateral occipital cortices and
      fMRI analysis confirmed high data quality with reliable activation in auditory,
      visual and frontal areas to the presentation of multisensory stimuli. In line
      with previous studies, we obtained reliable correlation patterns for event locked
      occipital alpha suppression and BOLD signal time course. Our results suggest a
      valid methodological approach to investigate complex stimuli using the present
      source localization driven method for EEG-fMRI. This novel procedure may help to
      investigate combined EEG-fMRI data from novel complex paradigms with high spatial
      and temporal resolution. 

PMID- 24294196
TI  - Dissociating task difficulty from incongruence in face-voice emotion integration.
AB  - In the everyday environment, affective information is conveyed by both the face
      and the voice. Studies have demonstrated that a concurrently presented voice can
      alter the way that an emotional face expression is perceived, and vice versa,
      leading to emotional conflict if the information in the two modalities is
      mismatched. Additionally, evidence suggests that incongruence of emotional
      valence activates cerebral networks involved in conflict monitoring and
      resolution. However, it is currently unclear whether this is due to task
      difficulty-that incongruent stimuli are harder to categorize-or simply to the
      detection of mismatching information in the two modalities. The aim of the
      present fMRI study was to examine the neurophysiological correlates of processing
      incongruent emotional information, independent of task difficulty. Subjects were
      scanned while judging the emotion of face-voice affective stimuli. Both the face
      and voice were parametrically morphed between anger and happiness and then paired
      in all audiovisual combinations, resulting in stimuli each defined by two
      separate values: the degree of incongruence between the face and voice, and the
      degree of clarity of the combined face-voice information. Due to the specific
      morphing procedure utilized, we hypothesized that the clarity value, rather than
      incongruence value, would better reflect task difficulty. Behavioral data
      revealed that participants integrated face and voice affective information, and
      that the clarity, as opposed to incongruence value correlated with categorization
      difficulty. Cerebrally, incongruence was more associated with activity in the
      superior temporal region, which emerged after task difficulty had been accounted
      for. Overall, our results suggest that activation in the superior temporal region
      in response to incongruent information cannot be explained simply by task
      difficulty, and may rather be due to detection of mismatching information between
      the two modalities. 

PMID- 24294197
TI  - Dissecting empathy: high levels of psychopathic and autistic traits are
      characterized by difficulties in different social information processing domains.
AB  - Individuals with psychopathy or autism spectrum disorder (ASD) can behave in ways
      that suggest lack of empathy towards others. However, many different cognitive
      and affective processes may lead to unempathic behavior and the social processing
      profiles of individuals with high psychopathic vs. ASD traits are likely
      different. Whilst psychopathy appears characterized by problems with resonating
      with others' emotions, ASD appears characterized by problems with cognitive
      perspective-taking. In addition, alexithymia has previously been associated with
      both disorders, but the contribution of alexithymia needs further exploration. In
      a community sample (N = 110) we show for the first time that although affective
      resonance and cognitive perspective-taking are related, high psychopathic traits
      relate to problems with resonating with others' emotions, but not cognitive
      perspective taking. Conversely, high ASD traits relate to problems with cognitive
      perspective-taking but not resonating with others' emotions. Alexithymia was
      associated with problems with affective resonance independently of psychopathic
      traits, suggesting that different component processes (reduced tendency to feel
      what others feel and reduced ability to identify and describe feelings) comprise
      affective resonance. Alexithymia was not associated with the reduced cognitive
      perspective-taking in high ASD traits. Our data suggest that (1) elevated
      psychopathic and ASD traits are characterized by difficulties in different social
      information processing domains and (2) reduced affective resonance in individuals
      with elevated psychopathic traits and the reduced cognitive perspective taking in
      individuals with elevated ASD traits are not explained by co-occurring
      alexithymia. (3) Alexithymia is independently associated with reduced affective
      resonance. Consequently, our data point to different component processes within
      the construct of empathy that are suggestive of partially separable cognitive and
      neural systems. 

PMID- 24294199
TI  - It's hard to forget: resetting memory in delay-match-to-multiple-image tasks.
AB  - The Delay-Match-to-Sample (DMS) task has been used in countless studies of
      memory, undergoing numerous modifications, making the task more and more
      challenging to participants. The physiological correlate of memory is modified
      neural activity during the cue-to-match delay period reflecting reverberating
      attractor activity in multiple interconnected cells. DMS tasks may use a fixed
      set of well-practiced stimulus images-allowing for creation of attractors-or
      unlimited novel images, for which no attractor exists. Using well-learned stimuli
      requires that participants determine if a remembered image was seen in the same
      or a preceding trial, only responding to the former. Thus, trial-to-trial
      transitions must include a "reset" mechanism to mark old images as such. We test
      two groups of monkeys on a delay-match-to-multiple-images task, one with well
      trained and one with novel images. Only the first developed a reset mechanism. We
      then switched tasks between the groups. We find that introducing fixed images
      initiates development of reset, and once established, switching to novel images
      does not disable its use. Without reset, memory decays slowly, leaving ~40%
      recognizable after a minute. Here, presence of reward further enhances memory of
      previously-seen images. 

PMID- 24294198
TI  - The neuromodulator of exploration: A unifying theory of the role of dopamine in
      personality.
AB  - The neuromodulator dopamine is centrally involved in reward, approach behavior,
      exploration, and various aspects of cognition. Variations in dopaminergic
      function appear to be associated with variations in personality, but exactly
      which traits are influenced by dopamine remains an open question. This paper
      proposes a theory of the role of dopamine in personality that organizes and
      explains the diversity of findings, utilizing the division of the dopaminergic
      system into value coding and salience coding neurons (Bromberg-Martin et al.,
      2010). The value coding system is proposed to be related primarily to
      Extraversion and the salience coding system to Openness/Intellect. Global levels
      of dopamine influence the higher order personality factor, Plasticity, which
      comprises the shared variance of Extraversion and Openness/Intellect. All other
      traits related to dopamine are linked to Plasticity or its subtraits. The general
      function of dopamine is to promote exploration, by facilitating engagement with
      cues of specific reward (value) and cues of the reward value of information
      (salience). This theory constitutes an extension of the entropy model of
      uncertainty (EMU; Hirsh et al., 2012), enabling EMU to account for the fact that
      uncertainty is an innate incentive reward as well as an innate threat. The theory
      accounts for the association of dopamine with traits ranging from sensation and
      novelty seeking, to impulsivity and aggression, to achievement striving,
      creativity, and cognitive abilities, to the overinclusive thinking characteristic
      of schizotypy. 

PMID- 24294200
TI  - Diverse sources of reward value signals in the basal ganglia nuclei transmitted
      to the lateral habenula in the monkey.
AB  - The lateral habenula (LHb) plays an important role in motivational decision
      making. Neurons in the primate LHb signal negative 'reward prediction errors' and
      inhibit midbrain dopamine (DA) neurons. These negative reward prediction error
      signals in the LHb are, at least partly, provided by a distinct group of neurons
      in the border region of the globus pallidus internal segment (GPb). However, it
      is still unclear whether other basal ganglia nuclei provide the LHb with reward
      signals, either through the GPb or through different circuits. As a first step to
      answer this question, we electrically stimulated various parts of the basal
      ganglia and monitored the neural activity in the LHb in the awake monkey. First,
      we found that low intensity stimulations in the GPb and the internal segment of
      the globus pallidus (GPi) evoked a short latency (5 ms) excitatory response in
      LHb neurons. Second, LHb neurons were inhibited by stimulations in the ventral
      pallidum (VP). These results suggest that reward-related signals are transmitted
      to the LHb mainly through excitatory connections from the GPb and inhibitory
      connections from the VP. Finally, excitations or inhibitions are induced in LHb
      neurons from diverse but patchy regions in the striatum. These effects have
      considerably longer latencies, suggesting that they may be mediated by the GPb or
      the VP. The patchy nature of the stimulation effect raises the possibility that
      the striosomes are the source of reward-related signals transmitted to the LHb. 

PMID- 24294201
TI  - Reduced Theta Connectivity during Set-Shifting in Children with Autism.
AB  - Autism spectrum disorder (ASD) is a characterized by deficits in social cognition
      and executive function. An area of particular difficulty for children with ASD is
      cognitive flexibility, such as the ability to shift between attentional or
      response sets. The biological basis of such deficits remains poorly understood,
      although atypical development of structural and functional brain connectivity
      have been reported in ASD, suggesting that disruptions of normal patterns of
      inter-regional communication may contribute to cognitive problems in this group.
      The present magnetoencephalography study measured inter-regional phase
      synchronization while children with ASD and typically developing matched controls
      (6-14 years of age) performed a set-shifting task. Reduced theta-band phase
      synchronization was observed in children with ASD during extradimensional set
      shifting. This reduction in task-dependent inter-regional connectivity
      encompassed numerous areas including multiple frontal lobe regions, and indicates
      that problems with communication among brain areas may contribute to difficulties
      with executive function in ASD. 

PMID- 24294202
TI  - The impact of binaural beats on creativity.
AB  - Human creativity relies on a multitude of cognitive processes, some of which are
      influenced by the neurotransmitter dopamine. This suggests that creativity could
      be enhanced by interventions that either modulate the production or transmission
      of dopamine directly, or affect dopamine-driven processes. In the current study
      we hypothesized that creativity can be influenced by means of binaural beats, an
      auditory illusion that is considered a form of cognitive entrainment that
      operates through stimulating neuronal phase locking. We aimed to investigate
      whether binaural beats affect creative performance at all, whether they affect
      divergent thinking, convergent thinking, or both, and whether possible effects
      may be mediated by the individual striatal dopamine level. Binaural beats were
      presented at alpha and gamma frequency. Participants completed a divergent and a
      convergent thinking task to assess two important functions of creativity, and
      filled out the Positive And Negative Affect Scale-mood State questionnaire (PANAS
      S) and an affect grid to measure current mood. Dopamine levels in the striatum
      were estimated using spontaneous eye blink rates (EBRs). Results showed that
      binaural beats, regardless of the presented frequency, can affect divergent but
      not convergent thinking. Individuals with low EBRs mostly benefitted from alpha
      binaural beat stimulation, while individuals with high EBRs were unaffected or
      even impaired by both alpha and gamma binaural beats. This suggests that binaural
      beats, and possibly other forms of cognitive entrainment, are not suited for a
      one-size-fits-all approach, and that individual cognitive-control systems need to
      be taken into account when studying cognitive enhancement methods. 

PMID- 24294203
TI  - Age differences in the intrinsic functional connectivity of default network
      subsystems.
AB  - Recent work suggests that the default mode network (DMN) includes two core
      regions, the ventromedial prefrontal cortex and posterior cingulate cortex (PCC),
      and several unique subsystems that are functionally distinct. These include a
      medial temporal lobe (MTL) subsystem, active during remembering and future
      projection, and a dorsomedial prefrontal cortex (dmPFC) subsystem, active during
      self-reference. The PCC has been further subdivided into ventral (vPCC) and
      dorsal (dPCC) regions that are more strongly connected with the DMN and cognitive
      control networks, respectively. The goal of this study was to examine age
      differences in resting state functional connectivity within these subsystems.
      After applying a rigorous procedure to reduce the effects of head motion, we used
      a multivariate technique to identify both common and unique patterns of
      functional connectivity in the MTL vs. the dmPFC, and in vPCC vs. dPCC. All four
      areas had robust functional connectivity with other DMN regions, and each also
      showed distinct connectivity patterns in both age groups. Young and older adults
      had equivalent functional connectivity in the MTL subsystem. Older adults showed
      weaker connectivity in the vPCC and dmPFC subsystems, particularly with other DMN
      areas, but stronger connectivity than younger adults in the dPCC subsystem, which
      included areas involved in cognitive control. Our data provide evidence for
      distinct subsystems involving DMN nodes, which are maintained with age.
      Nevertheless, there are age differences in the strength of functional
      connectivity within these subsystems, supporting prior evidence that DMN
      connectivity is particularly vulnerable to age, whereas connectivity involving
      cognitive control regions is relatively maintained. These results suggest an age
      difference in the integrated activity among brain networks that can have
      implications for cognition in older adults. 

PMID- 24294204
TI  - New advances in beta-blocker therapy in heart failure.
AB  - The use of beta-blockers (BB) in heart failure (HF) has been considered a
      contradiction for many years. Considering HF simply as a state of inadequate
      systolic function, BB were contraindicated because of their negative effects on
      myocardial contractility. Nevertheless, evidence collected in the past years have
      suggested that additional mechanisms, such as compensatory neuro-humoral
      hyperactivation or inflammation, could participate in the pathogenesis of this
      complex disease. Indeed, chronic activation of the sympathetic nervous system,
      although initially compensating the reduced cardiac output from the failing
      heart, increases myocardial oxygen demand, ischemia and oxidative stress;
      moreover, high catecholamine levels induce peripheral vasoconstriction and
      increase both cardiac pre- and after-load, thus determining additional stress to
      the cardiac muscle (1). As a consequence of such a different view of the
      pathogenic mechanisms of HF, the efficacy of BB in the treatment of HF has been
      investigated in numerous clinical trials. Results from these trials highlighted
      BB as valid therapeutic tools in HF, providing rational basis for their inclusion
      in many HF treatment guidelines. However, controversy still exists about their
      use, in particular with regards to the selection of specific molecules, since BB
      differ in terms of adrenergic beta-receptors selectivity, adjunctive effects on
      alpha-receptors, and effects on reactive oxygen species and inflammatory
      cytokines production. Further concerns about the heterogeneity in the response to
      BB, as well as the use in specific patients, are matter of debate among
      clinicians. In this review, we will recapitulate the pharmacological properties
      and the classification of BB, and the alteration of the adrenergic system
      occurring during HF that provide a rationale for their use; we will also focus on
      the possible molecular mechanisms, such as genetic polymorphisms, underlying the
      different efficacy of molecules belonging to this class. 

PMID- 24294206
TI  - Dimensional assessment of psychopathy and its relationship with physiological
      responses to empathic images in juvenile offenders.
AB  - OBJECTIVE: Many psychophysiological studies investigate whether psychopaths
      present low levels of electrodermal activity (EDA). However, despite evidence
      that varying degrees of psychopathy are normally distributed in the population,
      there is a paucity of EDA studies evaluating dimensionally. Moreover, although
      lack of empathy is a cornerstone of psychopathy, there has been a lack of studies
      using pictures of empathic emotional content to assess psychophysiological
      responses. METHOD: We studied a population of young male delinquents (n = 30)
      from a detention center, using the Psychopathy Checklist Revised (PCL-R) to
      determine if higher levels of psychopathy were related to lesser degrees of EDA
      in response to emotion-eliciting pictures of empathic content. RESULTS: There
      were significant correlations (p < 0.05) between latency and peak of EDA
      responses to unpleasant pictures and factor 1 scores, as well as between lability
      of EDA responses and factor 2 scores. CONCLUSION: These results extend previous
      findings indicating direct relationship between EDA and psychopathy, and suggest
      that separate investigations of the two PCL-R factors have the potential to
      unravel more complex relationships between EDA and psychopathy. Also, by
      demonstrating such associations using emotion-provoking stimuli with empathic
      content, our results provide a link between levels of psychopathy and biological
      indices of empathic detachment.

PMID- 24294205
TI  - Near-infrared spectroscopy in schizophrenia: a possible biomarker for predicting
      clinical outcome and treatment response.
AB  - Functional near-infrared spectroscopy (fNIRS) is a relatively new technique that
      can measure hemoglobin changes in brain tissues, and its use in psychiatry has
      been progressing rapidly. Although it has several disadvantages (e.g., relatively
      low spatial resolution and the possibility of shallow coverage in the depth of
      brain regions) compared with other functional neuroimaging techniques (e.g.,
      functional magnetic resonance imaging and positron emission tomography), fNIRS
      may be a candidate instrument for clinical use in psychiatry, as it can measure
      brain activity in naturalistic position easily and non-invasively. fNIRS
      instruments are also small and work silently, and can be moved almost everywhere
      including schools and care units. Previous fNIRS studies have shown that patients
      with schizophrenia have impaired activity and characteristic waveform patterns in
      the prefrontal cortex during the letter version of the verbal fluency task, and
      part of these results have been approved as one of the Advanced Medical
      Technologies as an aid for the differential diagnosis of depressive symptoms by
      the Ministry of Health, Labor and Welfare of Japan in 2009, which was the first
      such approval in the field of psychiatry. Moreover, previous studies suggest that
      the activity in the frontopolar prefrontal cortex is associated with their
      functions in chronic schizophrenia and is its next candidate biomarker. Future
      studies aimed at exploring fNIRS differences in various clinical stages,
      longitudinal changes, drug effects, and variations during different task
      paradigms will be needed to develop more accurate biomarkers that can be used to
      aid differential diagnosis, the comprehension of the present condition, the
      prediction of outcome, and the decision regarding treatment options in
      schizophrenia. Future fNIRS researches will require standardized measurement
      procedures, probe settings, analytical methods and tools, manuscript description,
      and database systems in an fNIRS community. 

PMID- 24294207
TI  - Causal inference of asynchronous audiovisual speech.
AB  - During speech perception, humans integrate auditory information from the voice
      with visual information from the face. This multisensory integration increases
      perceptual precision, but only if the two cues come from the same talker; this
      requirement has been largely ignored by current models of speech perception. We
      describe a generative model of multisensory speech perception that includes this
      critical step of determining the likelihood that the voice and face information
      have a common cause. A key feature of the model is that it is based on a
      principled analysis of how an observer should solve this causal inference problem
      using the asynchrony between two cues and the reliability of the cues. This
      allows the model to make predictions about the behavior of subjects performing a
      synchrony judgment task, predictive power that does not exist in other
      approaches, such as post-hoc fitting of Gaussian curves to behavioral data. We
      tested the model predictions against the performance of 37 subjects performing a
      synchrony judgment task viewing audiovisual speech under a variety of
      manipulations, including varying asynchronies, intelligibility, and visual cue
      reliability. The causal inference model outperformed the Gaussian model across
      two experiments, providing a better fit to the behavioral data with fewer
      parameters. Because the causal inference model is derived from a principled
      understanding of the task, model parameters are directly interpretable in terms
      of stimulus and subject properties. 

PMID- 24294209
TI  - Aftereffects in face processing.

PMID- 24294208
TI  - Negative correlation between leftward bias in line bisection and schizotypal
      features in healthy subjects.
AB  - INTRODUCTION: Recent studies have found a lack of normal pseudoneglect in
      schizophrenia patients and in their first degree relatives. Similarly, several
      contributions have reported that measures of schizotypy in the healthy population
      may be related to signs of right-sided lateralization, but most of these studies
      differ greatly in methodology (sample size, choice of schizotypy scales, and
      laterality tasks) and, consequently, the results cannot be compared and so
      definitive conclusion cannot be drawn. In this study, our purpose is to
      investigate whether some tasks of spatial attention may be related to different
      dimensions of schizotypy not only in a larger sample of healthy subjects (HS),
      but testing the same people with several supposedly related measures several
      times. MATERIALS AND METHODS: In the first part of the study (Part I), the
      performance on "paper and pencil" line bisection (LB) tasks in 205 HS was
      investigated. Each task was repeated three times. In the second part of the study
      (Part II), a subgroup of 80 subjects performed a computerized version of the LB
      test and of the mental number line bisection (MNL) test. In both parts of the
      study, every subject completed the 74-item version of the Schizotypal Personality
      Questionnaire (SPQ) and the Edinburgh Handedness Inventory (EHI). RESULTS: In
      both parts of the study, high scores on the subscale "magical thinking" of SPQ
      have resulted in being closely linked to a decreased pseudoneglect as assessed by
      the LB task. On the contrary, right handedness is related to an increased
      leftward bias at the same task. No association was found between MNL and the
      other variables. DISCUSSION: The main finding of this study is that a decreased
      spatial leftward bias at the LB task correlates with positive schizotypy in the
      healthy population. This finding supports the hypothesis that a deviation from
      leftward hemispatial visual preference may be related to the degree of psychosis
      like schizotypal signs in non-clinical population and should be investigated as a
      possible marker of psychosis.

PMID- 24294210
TI  - Causality within the Epileptic Network: An EEG-fMRI Study Validated by
      Intracranial EEG.
AB  - Accurate localization of the Seizure Onset Zone (SOZ) is crucial in patients with
      drug-resistance focal epilepsy. EEG with fMRI recording (EEG-fMRI) has been
      proposed as a complementary non-invasive tool, which can give useful additional
      information in the pre-surgical work-up. However, fMRI maps related to interictal
      epileptiform activities (IED) often show multiple regions of signal change, or
      "networks," rather than highly focal ones. Effective connectivity approaches like
      Dynamic Causal Modeling (DCM) applied to fMRI data potentially offers a framework
      to address which brain regions drives the generation of seizures and IED within
      an epileptic network. Here, we present a first attempt to validate DCM on EEG
      fMRI data in one patient affected by frontal lobe epilepsy. Pre-surgical EEG-fMRI
      demonstrated two distinct clusters of blood oxygenation level dependent (BOLD)
      signal increases linked to IED, one located in the left frontal pole and the
      other in the ipsilateral dorso-lateral frontal cortex. DCM of the IED-related
      BOLD signal favored a model corresponding to the left dorso-lateral frontal
      cortex as driver of changes in the fronto-polar region. The validity of DCM was
      supported by: (a) the results of two different non-invasive analysis obtained on
      the same dataset: EEG source imaging (ESI), and "psycho-physiological
      interaction" analysis; (b) the failure of a first surgical intervention limited
      to the fronto-polar region; (c) the results of the intracranial EEG monitoring
      performed after the first surgical intervention confirming a SOZ located over the
      dorso-lateral frontal cortex. These results add evidence that EEG-fMRI together
      with advanced methods of BOLD signal analysis is a promising tool that can give
      relevant information within the epilepsy surgery diagnostic work-up. 

PMID- 24294211
TI  - That's disturbing! An exploration of the bacteriophage biology of change.

PMID- 24294213
TI  - Complementarity of Binding Motifs is a General Property of HLA-A and HLA-B
      Molecules and Does Not Seem to Effect HLA Haplotype Composition.
AB  - Different human leukocyte antigen (HLA) haplotypes (i.e., the specific
      combinations of HLA-A, -B, -DR alleles inherited together from one parent) are
      observed in different frequencies in human populations. Some haplotypes, like HLA
      A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while
      others are very rare. Numerous studies have identified associations between HLA
      haplotypes and diseases, and differences in haplotype frequencies can in part be
      explained by these associations: the stronger the association with a severe
      (autoimmune) disease, the lower the expected HLA haplotype frequency. The peptide
      repertoires of the HLA molecules composing a haplotype can also influence the
      frequency of a haplotype. For example, it would seem advantageous to have HLA
      molecules with non-overlapping binding specificities within a haplotype, as
      individuals expressing such an haplotype would present a diverse set of peptides
      from viruses and pathogenic bacteria on the cell surface. To test this
      hypothesis, we collect the proteome data from a set of common viruses, and
      estimate the total ligand repertoire of HLA class I haplotypes (HLA-A-B) using in
      silico predictions. We compare the size of these repertoires to the HLA haplotype
      frequencies reported in the National Marrow Donor Program (NMDP). We find that in
      most HLA-A and HLA-B pairs have fairly distinct binding motifs, and that the
      observed haplotypes do not contain HLA-A and -B molecules with more distinct
      binding motifs than random HLA-A and HLA-B pairs. In addition, the population
      frequency of a haplotype is not correlated to the distinctness of its HLA-A and
      HLA-B peptide binding motifs. These results suggest that there is a not a strong
      selection pressure on the haplotype level favoring haplotypes having HLA
      molecules with distinct binding motifs, which would result the largest possible
      presented peptide repertoires in the context of infectious diseases. 

PMID- 24294212
TI  - Mechanisms of survival, responses and sources of Salmonella in low-moisture
      environments.
AB  - Some Enterobacteriaceae possess the ability to survive in low-moisture
      environments for extended periods of time. Many of the reported food-borne
      outbreaks associated with low-moisture foods involve Salmonella contamination.
      The control of Salmonella in low-moisture foods and their production environments
      represents a significant challenge for all food manufacturers. This review
      summarizes the current state of knowledge with respect to Salmonella survival in
      intermediate- and low-moisture food matrices and their production environments.
      The mechanisms utilized by this bacterium to ensure their survival in these dry
      conditions remain to be fully elucidated, however, in depth transcriptomic data
      is now beginning to emerge regarding this observation. Earlier research work
      described the effect(s) that low-moisture can exert on the long-term persistence
      and heat tolerance of Salmonella, however, data are also now available
      highlighting the potential cross-tolerance to other stressors including commonly
      used microbicidal agents. Sources and potential control measures to reduce the
      risk of contamination will be explored. By extending our understanding of these
      geno- and phenotypes, we may be able to exploit them to improve food safety and
      protect public health. 

PMID- 24294215
TI  - Uptake and regulation of resource allocation for optimal plant performance and
      adaptation to stress.

PMID- 24294214
TI  - Comparative transcript profiling by SuperSAGE identifies novel candidate genes
      for controlling potato quantitative resistance to late blight not compromised by
      late maturity.
AB  - Resistance to pathogens is essential for survival of wild and cultivated plants.
      Pathogen susceptibility causes major losses of crop yield and quality. Durable
      field resistance combined with high yield and other superior agronomic characters
      are therefore, important objectives in every crop breeding program. Precision and
      efficacy of resistance breeding can be enhanced by molecular diagnostic tools,
      which result from knowledge of the molecular basis of resistance and
      susceptibility. Breeding uses resistance conferred by single R genes and
      polygenic quantitative resistance. The latter is partial but considered more
      durable. Molecular mechanisms of plant pathogen interactions are elucidated
      mainly in experimental systems involving single R genes, whereas most genes
      important for quantitative resistance in crops like potato are unknown.
      Quantitative resistance of potato to Phytophthora infestans causing late blight
      is often compromised by late plant maturity, a negative agronomic character. Our
      objective was to identify candidate genes for quantitative resistance to late
      blight not compromised by late plant maturity. We used diagnostic DNA-markers to
      select plants with different field levels of maturity corrected resistance (MCR)
      to late blight and compared their leaf transcriptomes before and after infection
      with P. infestans using SuperSAGE (serial analysis of gene expression) technology
      and next generation sequencing. We identified 2034 transcripts up or down
      regulated upon infection, including a homolog of the kiwi fruit allergen
      kiwellin. 806 transcripts showed differential expression between groups of
      genotypes with contrasting MCR levels. The observed expression patterns suggest
      that MCR is in part controlled by differential transcript levels in uninfected
      plants. Functional annotation suggests that, besides biotic and abiotic stress
      responses, general cellular processes such as photosynthesis, protein
      biosynthesis, and degradation play a role in MCR. 

PMID- 24294216
TI  - Zn/Fe remobilization from vegetative tissues to rice seeds: should I stay or
      should I go? Ask Zn/Fe supply!

PMID- 24294218
TI  - Genetic associations with 25-hydroxyvitamin D deficiency in HIV-1-infected youth:
      fine-mapping for the GC/DBP gene that encodes the vitamin D-binding protein.
AB  - Serum 25-hydroxyvitamin D [25(OH)D] is often deficient (<12 ng/ml) or
      insufficient (<20 ng/ml) in youth living with human immunodeficiency virus type 1
      infection (YLH). Based on evidence from multiple genome-wide association studies,
      we hypothesized that genetic factors associated with 25(OH)D deficiency should be
      readily detectable in YLH even when controlling for other known factors,
      including use of the antiretroviral drug efavirenz (EFV). Genotyping by bi
      directional sequencing targeted 15 single nucleotide polymorphisms (SNPs) at the
      GC/DBP locus, with a focus on coding and regulatory variants, as well as those
      repeatedly reported in the literature. Three intronic SNPs (rs222016, rs222020,
      and rs222029) in a conserved haplotype block had unequivocal association signals
      (false discovery rate <= 0.006). In particular, the minor allele G for rs222020
      was highly unfavorable among 192 YLH (99 African-Americans and 93 others), as
      gauged by relatively low likelihood for 25(OH)D sufficiency at enrollment (odds
      ratio = 0.31, p = 9.0 * 10(-4)). In a reduced multivariable model, race, season,
      latitude, body mass index, exposure to EFV, and rs222020-G were independent
      factors that collectively accounted for 38% of variance in the log10-transformed
      25(OH)D concentration (p < 0.0001). Interaction terms were evident for rs222020-G
      * season (p < 0.001), latitude * season (especially fall and winter; p < 0.01),
      and race * EFV use (p = 0.024). Overall, variance in serum 25(OH)D is
      substantially attributable to multiple factors, but the exact contribution of
      genetic and non-genetic factors can be obscured by partial overlaps and frequent
      interactions. 

PMID- 24294219
TI  - Practice variation across consent templates for biobank research. a survey of
      German biobanks.
AB  - INTRODUCTION: Informed, voluntary, and valid consent from biomaterial donors is a
      precondition for biobank research. Valid consent protects donors' rights and
      helps maintain public trust in biobank research. Harmonization of consent
      procedures in biobank research is needed, because of the widely shared vision on
      national and international networking of biobanks including data and sample
      sharing. So far, no study has assessed and compared the content of current
      consent forms especially for biobank research. The objective of this study was to
      perform a content analysis of consent forms in German biobanks. METHODS: Based on
      ten guidelines for biomedical research, we developed an assessment matrix with 41
      content issues that are potentially relevant for consent forms in biobank
      research. This assessment matrix was applied in a thematic text analysis to 30
      consent documents of German biobanks identified via the German Biobank Registry
      in July 2012. RESULTS: Coverage of the 41 items in the assessed consent forms
      varied widely. For example, the items "Right to withdraw consent (without
      disadvantage)," "Policy for genetic information/consent to genetic analyzes" and
      "International cooperation/transborder use" were addressed in 97, 40, and 23% of
      all 30 consent forms respectively. The number of items covered by a single
      consent form ranged from 9 to 36 (22-88% out of 41 items). DISCUSSION: Our
      findings serve as a starting point to reflect upon the spectrum of consent issues
      that must be addressed in biobank research. The findings show that the majority
      of consent forms for German biobanks, if not all, should be improved and
      harmonized to better support an informed and balanced choice of potential donors
      and to facilitate networking of biobanks. Best practice models for consent forms
      in biobank research should be developed and biobank operators need to be more
      aware of relevant consent issues.

PMID- 24294217
TI  - Thiol-based redox regulation in sexual plant reproduction: new insights and
      perspectives.
AB  - The success of sexual reproduction in plants involves (i) the proper formation of
      the plant gametophytes (pollen and embryo sac) containing the gametes, (ii) the
      accomplishment of specific interactions between pollen grains and the stigma,
      which subsequently lead to (iii) the fusion of the gametes and eventually to (iv)
      the seed setting. Owing to the lack of mobility, plants have developed specific
      regulatory mechanisms to control all developmental events underlying the sexual
      plant reproduction according to environmental challenges. Over the last decade,
      redox regulation and signaling have come into sight as crucial mechanisms able to
      manage critical stages during sexual plant reproduction. This regulation involves
      a complex redox network which includes reactive oxygen species (ROS), reactive
      nitrogen species (RNS), glutathione and other classic buffer molecules or
      antioxidant proteins, and some thiol/disulphide-containing proteins belonging to
      the thioredoxin superfamily, like glutaredoxins (GRXs) or thioredoxins (TRXs).
      These proteins participate as critical elements not only in the switch between
      the mitotic to the meiotic cycle but also at further developmental stages of
      microsporogenesis. They are also implicated in the regulation of pollen rejection
      as the result of self-incompatibility. In addition, they display precise space
      temporal patterns of expression and are present in specific localizations like
      the stigmatic papillae or the mature pollen, although their functions and
      subcellular localizations are not clear yet. In this review we summarize insights
      and perspectives about the presence of thiol/disulphide-containing proteins in
      plant reproduction, taking into account the general context of the cell redox
      network. 

PMID- 24294220
TI  - Microbiological, technological and therapeutic properties of kefir: a natural
      probiotic beverage.
AB  - Kefir is a fermented milk beverage produced by the action of bacteria and yeasts
      that exist in symbiotic association in kefir grains. The artisanal production of
      the kefir is based on the tradition of the peoples of Caucasus, which has spread
      to other parts of the world, from the late 19(th) century, and nowadays
      integrates its nutritional and therapeutic indications to the everyday food
      choices of several populations. The large number of microorganisms present in
      kefir and their microbial interactions, the possible bioactive compounds
      resulting of microbial metabolism, and the benefits associated with the use this
      beverage confers kefir the status of a natural probiotic, designated as the
      21(th) century yoghurt. Several studies have shown that kefir and its
      constituents have antimicrobial, antitumor, anticarcinogenic and immunomodulatory
      activity and also improve lactose digestion, among others. This review includes
      data on the technological aspects, the main beneficial effects on human health of
      kefir and its microbiological composition. Generally, kefir grains contain a
      relatively stable and specific microbiota enclosed in a matrix of polysaccharides
      and proteins. Microbial interactions in kefir are complex due to the composition
      of kefir grains, which seems to differ among different studies, although some
      predominant Lactobacillus species are always present. Besides, the specific
      populations of individual grains seem to contribute to the particular sensory
      characteristics present in fermented beverages. This review also includes new
      electron microscopy data on the distribution of microorganisms within different
      Brazilian kefir grains, which showed a relative change in its distribution
      according to grain origin. 

PMID- 24294221
TI  - Recombinants proteins for industrial uses: utilization of Pichia pastoris
      expression system.
AB  - The innovation in industrial process with impact in the efficient production is
      the major challenge for actual industry. A high numerous of enzymes are utilized
      in at different level of process; the search for new alternatives with better
      characteristic has become a field of study of great interest, the recombinant
      protein achievement in a different host system is an alternative widely assessed
      for production of this. The microorganism Pichia pastoris has been used like a
      successful expression system in diverse areas, improved the yield and extraction
      recovery of the product expressed. The reported of diverse authors in the
      production of enzymes with different application in industry is varied, in this
      review the different industry areas and the characteristic of the enzymes
      produced are detailed. 

PMID- 24294222
TI  - Inhibitory activity of Syzygium aromaticum and Cymbopogon citratus (DC.) Stapf.
      essential oils against Listeria monocytogenes inoculated in bovine ground meat.
AB  - This research evaluated the antimicrobial effect of the clove (Syzygium
      aromaticum) and lemongrass (Cymbopogon citratus (DC.) Stapf.) essential oils
      (EOs) against Listeria monocytogenes ATCC 19117 growth added to bovine ground
      meat stored under refrigeration (5 +/- 2  degrees C) for three days. The EOs,
      extracted by hydrodistillation and analyzed by gas chromatography-mass
      spectrometry (GC-MS), were tested in vitro using an agar well diffusion
      methodology for determination of Minimum Inhibitory Concentration (MIC). The MIC
      concentrations for both essential oils on culture tested of L. monocytogenes were
      1.56%. The EOs concentrations applied in contaminated ground beef were 1.56,
      3.125 and 6.25% (w/v) based on MIC levels and possible activity reductions by
      food constituents. The bacteria populations were significantly reduced (p <=
      0.05) after one day of storage in ground meat samples treated with clove and
      lemongrass EOs at concentrations of 1.56%. There were no significant counts of L.
      monocytogenes in samples at the other concentrations of the two oils applied
      after the second day of storage. The sensory acceptability evaluation of the
      bovine ground meat samples treated with EOs showed that the addition at
      concentrations higher than 1.56% promote undesirable alterations of taste, odor
      and characteristic color. The application of EOs at low concentrations in food
      products can be used in combination with other preservation methods, such as
      refrigeration, to control pathogens and spoilage bacteria during shelf-life;
      which goes according to current market trends, where consumers are requesting
      natural products. 

PMID- 24294223
TI  - Commercially laid eggs vs. discarded hatching eggs: contamination by Salmonella
      spp.
AB  - Salmonella enterica is frequently associated with outbreaks of human
      salmonellosis, and products of avian origin, such as eggs and chicken meat, are
      the main vehicles of its transmission. The present study describes the occurrence
      of different serovars of Salmonella enterica and phagotypes of S. enterica
      serovar Enteritidis in eggs destined for human consumption. Four thousand eggs
      obtained from commercial egg laying farms and one thousand discarded hatching
      eggs from broiler farms, which were acquired at farmers' markets and informal
      shops, were analyzed. Salmonella spp. was isolated from 52.0% of the discarded
      hatching eggs, in which the predominant serovar was Enteritidis (84.6%), and the
      predominant Salmonella Enteritidis phagotype (PT) was PT7 (26.9%). Salmonella
      spp. was not isolated from eggs obtained from commercial egg laying farms. The
      antimicrobial resistance profile showed that 23.1% (n = 6) of the SE strains were
      resistant to nalidixic acid. The results suggest that the consumption of
      discarded hatching eggs represents an important source of Salmonella transmission
      to humans. 

PMID- 24294224
TI  - Occurrence of zearalenone in wheat- and corn-based products commercialized in the
      State of Parana, Brazil.
AB  - The productivity of wheat and corn crops depends on climatic conditions and
      resistance against phytopathogenic fungi such as those of the genus Fusarium.
      Some species of this genus produce zearalenone (ZEA), a mycotoxin with
      hyperestrogenic effects. The objective of this study was to investigate the
      presence of ZEA in samples of cracked wheat (n = 109), popcorn (n = 51) and corn
      grits (n = 50) commercialized in the State of Parana, Brazil. Commercial samples
      of each crop were collected between September 2007 and June 2008 and analyzed by
      thin-layer chromatography. The method used for detection of the mycotoxin in
      wheat and corn derivatives presented a recovery rate of 94.5% and 99.5%,
      respectively, detection limit of 40 MUg.kg(-1) and quantification limit of 55
      MUg.kg(-1). No contamination with ZEA was detected in cracked wheat samples.
      Among the corn derivatives, only one cracked corn sample was contaminated with
      ZEA (64 MUg.kg(-1)). Despite the low contamination observed, monitoring the
      occurrence of mycotoxins in foods is important to ensure safety. 

PMID- 24294225
TI  - Ochratoxigenic fungi associated with green coffee beans (Coffea arabica L.) in
      conventional and organic cultivation in Brazil.
AB  - The genera Aspergillus comprises species that produce mycotoxins such as
      aflatoxins, ochratoxins and patulin. These are cosmopolitan species, natural
      contaminants of agricultural products. In coffee grains, the most important
      Aspergillus species in terms of the risk of presenting mycotoxins belong to the
      genera Aspergillus Section Circumdati and Section Nigri. The purpose of this
      study was to assess the occurrence of isolated ochratoxigenic fungi of coffee
      grains from organic and conventional cultivation from the South of Minas Gerais,
      Brazil, as well as to evaluate which farming system presents higher contamination
      risk by ochratoxin A (OTA) produced by fungi. Thirty samples of coffee grains
      (Coffea arabica L.) were analysed, being 20 of them of conventional coffee grains
      and 10 of them organic. The microbiological analysis was done with the Direct
      Plating Technique in a Dichloran Rose Bengal Chloramphenicol Agar (DRBC) media.
      The identification was done based on the macro and micro morphological
      characteristics and on the toxigenic potential with the Plug Agar technique. From
      the 30 samples analysed, 480 filamentous fungi of the genera Aspergillus of the
      Circumdati and Nigri Sections were isolated. The ochratoxigenic species
      identified were: Aspergillus auricoumus, A. ochraceus, A. ostianus, A. niger and
      A. niger Aggregate. The most frequent species which produces ochratoxin A among
      the isolated ones was A. ochraceus, corresponding to 89.55%. There was no
      significant difference regarding the presence of ochratoxigenic A. ochreceus
      between the conventional and organic cultivation systems, which suggests that the
      contamination risk is similar for both cultivation systems. 

PMID- 24294226
TI  - Characterization of antibiotic resistance in Salmonella enterica isolates
      determined from ready-to-eat (RTE) salad vegetables.
AB  - In the last decade, ready-to-eat (RTE) salad vegetables are gaining increasing
      importance in human diet. However, since they are consumed fresh, inadequate
      washing during processing can bring on some foodborne illnesses, like
      salmonellosis, since these food items have natural contamination from soil and
      water. During 2009-2010, a total of 81 samples were purchased arbitrarily from
      local markets in Ankara, and were examined for Salmonella contamination.
      Salmonella screening was performed by using anti-Salmonella magnetic beads system
      and polymerase chain reaction (PCR) identification of the suspected colonies.
      Then, the antibiotic resistance profiles of four Salmonella strains identified
      (strains RTE-1, RTE-2, RTE-3, and RTE-4) were also investigated, since the
      mechanism by which Salmonella spp. have accumulated antibiotic resistance genes
      is of interest. All strains showed resistance against sulfonamides (MIC > 128
      mg/L). Further results suggested that associated sulfonamide resistance genes
      were encoded by the 55.0 kb plasmid of strain RTE-1 that involves no integrons.
      As a result of using two primers (P1254 and P1283) in randomly amplified
      polymorphic DNA-PCR (RAPD-PCR) analysis, two common amplicons (364 bp and 1065
      bp) were determined. The findings of this study provide support to the adoption
      of guidelines for the prudent use of antibiotics in order to reduce the number of
      pathogens present on vegetable and fruit farms. Besides, since it is shown that
      these bacteria started to gain resistance to antibiotics, it is necessary to
      further investigate the prevalence of them in foods. 

PMID- 24294227
TI  - Enterotoxigenicity of Staphylococcus aureus isolated from traditional and
      commercial dairy products marketed in Iran.
AB  - This study was conducted to determine the prevalence rate, enterotoxigenecity,
      and antimicrobial resistance of S. aureus isolated from dairy products in Iran.
      From September 2010 to July 2011, a total of 347 samples from various dairy
      products, traditional and commercial, were collected from randomly selected
      retail stores. Overall, 20 samples (5.8%) were found to be contaminated with S.
      aureus. The highest prevalence of S. aureus was found in traditional cheese
      (11.1%), followed by traditional ice-cream (5.9%), cream (5.6%), and butter
      (5.3%). The ability to synthesize classical staphylococcal enterotoxins (SEA-E)
      was determined in 7 of 20 (35%) isolates by using ELISA. SE type C was the most
      common enterotoxin found in the isolated S. aureus (42.9%), followed by SE type A
      (28.6%), SEA+SEC and SE type D (14.3%). Of the 20 isolates, 16 (80.0%) were
      positive for one or more entrotoxin genes and 8 different genotypes were
      observed. Susceptibilities of the isolates were determined for 14 antimicrobial
      drugs using the disk diffusion assay. Most of the isolates (95.0%) were resistant
      to one or more two antimicrobial agent and 45.0% of the isolates were resistant
      to three or more of drugs. Resistance to ampicillin was the most common finding
      (55.0%), followed by tetracycline (40.0%) and penicillin G (30.0%). The results
      of this study showed the wide spread of enterotoxigenic and multidrug-resistant
      S. aureus strains in traditional dairy products in Iran and highlighted their
      public health hazards. 

PMID- 24294228
TI  - Incidence and multiplex PCR based detection of trichothecene chemotypes of
      Fusarium culmorum isolates collected from freshly harvested Maize kernels in
      Southern India.
AB  - Hundred Fusarium culmorum strains, isolated from freshly harvested maize grain
      samples from Southern parts of India, were incubated in czapek-dox medium and
      analyzed for trichothecene (DON/NIV) production. The mPCR assay was standardized
      targeting trichothecene metabolic pathway genes viz., Tri6, Tri7, Tri13 for
      detection of trichothecene (DON/NIV) chemotypes and rDNA gene for specific
      detection of F. culmorum species. Primers for targeted genes were designed and
      used to predict whether these isolates could produce deoxynivalenol/nivalenol, 94
      isolates were able to produce DON/NIV by mPCR assay. Chemical analysis of DON/NIV
      was carried out for mPCR positive isolates by high performance-thin layer
      chromatography (HPTLC). To check the practical usefulness of developed mPCR
      assay, 150 field samples of maize were evaluated and results were compared with
      conventional HPTLC method. Out of 150 samples, 34% samples stayed as a positive
      for NIV contamination whereas 44% were found to have deoxynivalenol
      contamination. Moreover, mPCR results are equivocally matched with the HPTLC
      chemical analysis for field samples. Chemotyping of F. culmorum isolates were
      reported for the first time from India, and highlights the important potential of
      F. culmorum to contaminate maize with DON/NIV. 

PMID- 24294229
TI  - The influences of fish infusion broth on the biogenic amines formation by lactic
      acid bacteria.
AB  - The influences of fish infusion decarboxylase broth (IDB) on biogenic amines (BA)
      formation by lactic acid bacteria (LAB) were investigated. BA productions by
      single LAB strains were tested in five different fish (anchovy, mackerel, white
      shark, sardine and gilthead seabream) IDB. The result of the study showed that
      significant differences in ammonia (AMN) and BA production were observed among
      the LAB strains in fish IDB (p < 0.05). The highest AMN and TMA production by LAB
      strains were observed for white shark IDB. The all tested bacteria had
      decarboxylation activity in fish IDB. The uppermost accumulated amines by LAB
      strains were tyramine (TYM), dopamine, serotonin and spermidine. The maximum
      histamine production was observed in sardine (101.69 mg/L) and mackerel (100.84
      mg/L) IDB by Leuconostoc mesenteroides subsp. cremoris and Pediococcus
      acidophilus, respectively. Lactobacillus delbrueckii subsp. lactis and
      Pediococcus acidophilus had a high TYM producing capability (2943 mg/L and 1157
      mg/L) in sardine IDB. 

PMID- 24294230
TI  - Toxigenic potential of Fusarium graminearum isolated from maize of northwest
      Argentina.
AB  - Twenty six isolates of Fusarium graminearum from grains of maize hybrids
      harvested in +/-west Argentina were grown on autoclaved rice grain to assess
      their ability to produce type B trichothecenes. Chemical analysis indicated that
      38% of isolates were nivalenol (NIV) producers only, 31% were major NIV producers
      with high DON(deoxynivalenol)/NIV ratios, 8% were major DON producers with minor
      NIV production, and 23% were DON producers only. Isolates showed a high
      variability in their toxigenic potential which was not related to fungal biomass.
      The distribution of the different chemotypes as well as the high and the low
      trichothecene-producing Fusarium isolates could not be associated to a
      geographical origin. Our results confirmed for the first time that isolates of
      Fusarium graminearum from maize of northwest Argentina are able to produce DON
      and NIV. A substancial contamination with both NIV and DON is likely in maize
      from northwest Argentina. Their contents should be quantified in regional
      surveillances for mycotoxin contamination. 

PMID- 24294231
TI  - Biofilm formation on polystyrene under different temperatures by antibiotic
      resistant Enterococcus faecalis and Enterococcus faecium isolated from food.
AB  - The ability of antibiotic resistant E. faecalis and E. faecium isolated from food
      to form biofilm at different temperatures in the absence or presence of 0.75%
      glucose was evaluated. A synergistic effect on biofilm at 10  degrees C, 28 
      degrees C, 37  degrees C and 45  degrees C and glucose was observed for E.
      faecalis and E. faecium. 

PMID- 24294232
TI  - Phenotypic and genotypic characterization of lactic acid bacteria isolated from
      cow, ewe and goat dairy artisanal farmhouses.
AB  - Lactic acid bacteria collected from artisanal farmhouses were characterized using
      a polyphasic approach. Phenotypic methods including biochemical assays, ribosomal
      DNA restriction analysis and 16S rDNA sequence analysis were performed. This
      approach provides accuracy for identification, and helps to avoid the loss of
      natural biodiversity including potentially valuable strains. 

PMID- 24294233
TI  - Influence of fructooligosaccharides on the fermentation profile and viable counts
      in a symbiotic low fat milk.
AB  - This study evaluated the effects of prebiotics on fermentation profile and growth
      of Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus,
      and Bifidobacterium lactis in co-cultures with Streptococcus thermophilus.
      Acidification rate and viability were positively influenced by the co-culture
      with B. lactis and by both inulin or oligofructose in low fat milk. 

PMID- 24294234
TI  - Carbapenem and cefoxitin resistance of Klebsiella pneumoniae strains associated
      with porin OmpK36 loss and DHA-1 beta-lactamase production.
AB  - Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae)
      strains are being increased worldwide. Five pan-resistant K. pneumoniae strains
      have been isolated from respiratory and ICU wards in a Chinese hospital, and
      reveal strong resistance to all beta-lactams, fluoroquinolones and
      aminoglycosides. Totally 27 beta-lactamase genes and 2 membrane pore protein
      (porin) genes in 5 K. pneumoniae strains were screened by polymerase chain
      reaction (PCR). The results indicated that all of 5 K. pneumoniae strains carried
      blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or
      OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the resistant isolates
      markedly lacked the protein band of 34-40 kDa, which might be the outer membrane
      proteins of OmpK36 according to the electrophoresis mobility. In addition, the
      conjugation test was confirmed that blaDHA-1 mediated by plasmids could be
      transferred between resistant and sensitive strains. When reserpine (30 MUg/mL)
      and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 MUg/mL) were added in
      imipenem and meropenem, the MICs had no change against K. pneumoniae strains.
      These results suggest that both DHA-1 beta-lactamase and loss or deficiency of
      porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance
      in K. pneumoniae strains in our hospital. 

PMID- 24294235
TI  - Dermatophytosis diagnosed at the Evandro Chagas Institute, Para, Brazil.
AB  - Dermatophytosis is caused by a dermatophyte fungus that affects the stratum
      corneum and keratinized tissue. Dermatophyte fungus has been reported worldwide
      as the causative agent of dermatophytosis, but the etio-epidemiological aspects
      of these mycoses in the state of Para remain unknown. The purpose of this study
      was to describe the etio-epidemiological profile of dermatophytosis diagnosed in
      patients at the Evandro Chagas Institute from May 2005 to June 2006. A total of
      494 patients were admitted, and their samples were collected, submitted for
      direct microscopic examination using 20% KOH and cultured in Sabouraud and
      Mycosel medium. The identification was based in macro and microscopic
      characteristics. Direct examinations were positive in 13% (66/494) of the
      patients, and agent isolation by cultivation of the biological sample was
      successful in 4% (20/494), with a high prevalence of T. mentagrophytes (40%;
      8/20). Dermatophytosis was more frequent in women (58%; 38/66). Fifty-two percent
      (21/38) of the cases were children with an average age of 8 years. The most
      frequent clinical presentation was Tinea corporis (55%, 36/66). For the cases in
      which the dermatophyte agent was not isolated, we discuss the factors that may be
      interfering with isolation. Tinea corporis occurred more frequently observed when
      T. mentagrophytes and T. rubrum were the major etiologic agents. 

PMID- 24294236
TI  - Toxigenic profile and AFLP variability of Alternaria alternata and Alternaria
      infectoria occurring on wheat.
AB  - The objectives of this study were to evaluate the ability to produce alternariol
      (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TA) by A.
      alternata and A. infectoria strains recovered from wheat kernels obtained from
      one of the main production area in Argentina; to confirm using AFLPs molecular
      markers the identify of the isolates up to species level, and to evaluate the
      intra and inter-specific genetic diversity of these two Alternaria species. Among
      all the Alternaria strains tested (254), 84% of them were able to produce
      mycotoxins. The most frequent profile of toxin production found was the co
      production of AOH and AME in both species tested. TA was only produced by strains
      of A. alternata. Amplified fragment polymorphism (AFLPs) analysis was applied to
      a set of 89 isolates of Alternaria spp (40 were A. infectoria and 49 were A.
      alternata) in order to confirm the morphological identification. The results
      showed that AFLPs are powerful diagnostic tool for differentiating between A.
      alternata and A. infectoria. Indeed, in the current study the outgroup strains,
      A. tenuissima was consistently classified. Characteristic polymorphic bands
      separated these two species regardless of the primer combination used. Related to
      intraspecific variability, A. alternata and A. infectoria isolates evaluated
      seemed to form and homogeneous group with a high degree of similarity among the
      isolates within each species. However, there was more scoreable polymorphism
      within A. alternata than within A. infectoria isolates. There was a concordance
      between morphological identification and separation up to species level using
      molecular markers. Clear polymorphism both within and between species showed that
      AFLP can be used to asses genetic variation in A. alternata and A. infectoria.
      The most important finding of the present study was the report on AOH and AME
      production by A. infectoria strains isolated from wheat kernels in Argentina on a
      semisynthetic media for the first time. Also, specific bands for A. alternata and
      A. infectoria have been identified; these may be useful for the design of
      specific PCR primers in order to differentiate these species and to detect them
      in cereals. 

PMID- 24294237
TI  - Antimicrobial effect of para-alkoxyphenylcarbamic acid esters containing
      substituted N-phenylpiperazine moiety.
AB  - In current research, nine basic esters of para-alkoxyphenylcarbamic acid with
      incorporated 4-(4-fluoro-/3-trifluoromethylphenyl)piperazin-1-yl fragment, 6i-6m
      and 8f-8i, were screened for their in vitro antimicrobial activity against
      Candida albicans, Staphylococcus aureus and Escherichia coli, respectively.
      Taking into account the minimum inhibitory concentration assay (MIC), as the most
      active against given yeast was evaluated 8i (MIC = 0.20 mg/mL), the most
      lipophilic structure containing para-butoxy and trifluoromethyl substituents.
      Investigating the efficiency of the compounds bearing only a single atom of
      fluorine and appropriate para-alkoxy side chain against Candida albicans, the cut
      off effect was observed. From evaluated homological series, the maximum of the
      effectiveness was noticed for the stucture 6 k (MIC = 0.39 mg/mL), containing
      para-propoxy group attached to phenylcarbamoyloxy fragment, beyond which the
      compounds ceased to be active. On the contrary, all the tested molecules were
      against Staphylococcus aureus and Escherichia coli (MICs > 1.00 mg/mL)
      practically inactive. 

PMID- 24294238
TI  - Viability of stressed Mycobacterium tuberculosis and association with multidrug
      resistance.
AB  - This study investigated biological characteristics of recovered stressed M.
      tuberculosis isolates that failed to grow in differential culture media for
      phenotypic identification and in culture media containing anti-tuberculosis drugs
      for drug-susceptibility testing, despite of having grown in primary culture. It
      represents an improvement in the diagnosis of MDR tuberculosis and tuberculosis
      control. 

PMID- 24294239
TI  - Extended-spectrum beta-lactamase-producing enterobacteriaceae in community
      acquired urinary tract infections in Sao Luis, Brazil.
AB  - The number of ESBL-producing Enterobacteriaceae in community-acquired urinary
      tract infections worldwide is probably underestimated because of the technical
      difficulties encountered with their detection. In this study, out of 5,672 urine
      samples analyzed, 916 were positive for uropathogens, 472 of them being
      enterobacteria of which 7.6% produced beta-lactamases. Analysis of the isolated
      from 36 patients showed a high level of antibiotic resistance, with 52.7% and
      80.5% of isolates expressing bla TEM and bla CTX-M, respectively. 

PMID- 24294240
TI  - Pasteurella multocida bacterial meningitis caused by contact with pigs.
AB  - Pasteurella multocida belongs to the normal flora of the respiratory and
      digestive tract of many animals. Animal exposure is a considerable risk factor
      for Pasteurella infection. P. multocida is the most common cause of local
      infection after an animal bite but is an unusual cause of meningitis. We present
      a case of bacterial meningitis by P. multocida in a 37-year-old man who worked in
      a pig farm and was bitten by a pig. The patient had a defect located in the
      lamina cribosa and this lesion could be the gateway of the infection, although in
      this case the infection could also be acquired through the pig bite. The bacteria
      was identified as P. multocida with the biochemical test API 20E (bioMerieux). In
      agreement with findings in the literature, the strain was susceptible in vitro to
      penicillin, ampicillin, cefotaxime, ceftriaxone ciprofloxacin, levofloxacin,
      imipenem and tetracycline. 

PMID- 24294241
TI  - A fatal case of urosepsis due to Corynebacterium riegelii.
AB  - Corynebacterium species other than Corynebacterium diphtheriae rarely cause
      infections in human but rather reside in flora, however they have been reported
      to cause opportunistic infections in both immunocompromised and immunecompetent
      patients. Here we report for the first time a case of an elderly female patient
      presenting with a fatal urosepsis caused by a recently defined pathogen,
      Corynebacterium riegelii, identified on second day after patient hospitalization
      leading to a progressive worsening and death of the patient on 6th day. 

PMID- 24294242
TI  - Frequency of plasmid-mediated AmpC in Enterobacteriaceae isolated in a Brazilian
      Teaching Hospital.
AB  - In Brazil, the presence of plasmid-mediated AmpC (pAmpC)-producing isolates has
      been sporadically reported. We evaluated the frequency of pAmpC among 133
      Enterobacteriaceae clinical isolates. The bla CMY-2-like gene was detected in a
      single Klebsiella pneumoniae isolate. In our study, the pAmpC frequency was very
      low as previously reported. 

PMID- 24294243
TI  - In vitro activity of disinfectants against Aspergillus spp.
AB  - Fungi of the Aspergillus genus are widespread and contaminate the environment.
      Thousands of conidia are released from each phialide and dispersed in the air
      every day. These fungi are considered important mycose-causing agents in
      hospitals. Due to this, research to determine prevalent fungi from the
      Aspergillus genus in hospital environments, and an adequate disinfection program
      in these areas is are needed. This study evaluated the susceptibility of
      Aspergillus spp. isolated from a veterinary environment against four
      disinfectants. Successive dilutions of disinfectants (log2) were used according
      to CLSI M38-A2 microdilution technique adapted to chemical agents against 18
      isolates of this genus. After 72 hours of incubation, the Minimum Inhibiting
      Concentration and Minimum Fungicidal Concentration capable of inhibiting 50% and
      90% of the isolates were determined. Chlorexidine-cetrimine, benzalconium
      chloride and a chlorophenol derivative proved to be effective against all
      isolates with a lower MIC than that suggested by the manufacturer, except for the
      A. flavus strain. Sodium hypochlorite was ineffective against three A. fumigatus,
      three A. flavus and one A. niger isolate. These results demonstrated that all
      studied disinfectants were effective against environmental isolates, with the
      exception of sodium hypochlorite, which showed lower effectiveness. 

PMID- 24294244
TI  - Identification of pathogens and virulence profile of Rhodococcus equi and
      Escherichia coli strains obtained from sand of parks.
AB  - The identification of pathogens of viral (Rotavirus, Coronavirus), parasitic
      (Toxocara spp.) and bacterial (Escherichia coli, Salmonella spp., Rhodococcus
      equi) origin shed in feces, and the virulence profile of R. equi and E. coli
      isolates were investigated in 200 samples of sand obtained from 40 parks, located
      in central region of state of Sao Paulo, Brazil, using different diagnostic
      methods. From 200 samples analyzed, 23 (11.5%) strains of R. equi were isolated.
      None of the R. equi isolates showed a virulent (vapA gene) or intermediately
      virulent (vapB gene) profiles. Sixty-three (31.5%) strains of E. coli were
      identified. The following genes encoding virulence factors were identified in E.
      coli: eae, bfp, saa, iucD, papGI, sfa and hly. Phylogenetic classification showed
      that 63 E. coli isolates belonged to groups B1 (52.4%), A (25.4%) and B2 (22.2%).
      No E. coli serotype O157:H7 was identified. Eggs of Toxocara sp. were found in
      three parks and genetic material of bovine Coronavirus was identified in one
      sample of one park. No Salmonella spp. and Rotavirus isolates were identified in
      the samples of sand. The presence of R. equi, Toxocara sp, bovine Coronavirus and
      virulent E. coli isolates in the environment of parks indicates that the sanitary
      conditions of the sand should be improved in order to reduce the risks of fecal
      transmission of pathogens of zoonotic potential to humans in these places. 

PMID- 24294245
TI  - Comparative analysis of agr groups and virulence genes among subclinical and
      clinical mastitis Staphylococcus aureus isolates from sheep flocks of the
      Northeast of Brazil.
AB  - Staphylococcus aureus is one of the most frequent mastitis causative agents in
      small ruminants. The expression of most virulence genes of S. aureus is
      controlled by an accessory gene regulator (agr) locus. This study aimed to
      ascertain the prevalence of the different agr groups and to evaluate the
      occurrence of encoding genes for cytotoxin, adhesins and toxins with superantigen
      activity in S. aureus isolates from milk of ewes with clinical and subclinical
      mastitis in sheep flocks raised for meat production The agr groups I and II were
      identified in both cases of clinical and subclinical mastitis. Neither the arg
      groups III and IV nor negative agr were found. The presence of cflA gene was
      identified in 100% of the isolates. The frequency of hla and lukE-D genes was
      high - 77.3 and 82.8%, respectively and all isolates from clinical mastitis
      presented these genes. The sec gene, either associated to tst gene or not, was
      identified only in isolates from subclinical mastitis. None of the following
      genes were identified: bbp, ebpS, cna, fnbB, icaA, icaD, bap, hlg, lukM-lukF-PV
      and se-a-b-d-e. 

PMID- 24294246
TI  - Action of phosphorylated mannanoligosaccharides on immune and hematological
      responses and fecal consistency of dogs experimentally infected with
      enteropathogenic Escherichia coli strains.
AB  - The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was
      investigated regarding its prebiotic activity on enteropathogenic Escherichia
      coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC
      strains. Then MOS was supplied once a day, in water for 20 days. Immunological
      (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and
      bacteriological variables (PCR detection of the eae gene of EPEC recovered from
      stool culture), as well as occurrence of diarrhea were evaluated. All strains
      caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E.
      coli isolated from stool culture of all infected animals had the eae gene. There
      was no significant difference among groups as to number of blood cells in the
      hemogram and IgA and IgG production. MOS was effective in recovering of EPEC
      infected dogs since prebiotic-treated animals recovered more rapidly from
      infection than untreated ones (p < 0.05). This is an important finding since
      diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for
      humans and other animals with diarrhea can be an alternative for the treatment
      and prophylaxis of EPEC infections. 

PMID- 24294247
TI  - A Multiplex real-time PCR for detection of Mycoplasma gallisepticum and
      Mycoplasma synoviae in clinical samples from Brazilian commercial poultry flocks.
AB  - Mycoplasma gallisepticum (MS) and Mycoplasma synoviae (MS) are important avian
      pathogens and cause economic losses to the poultry industry. Molecular biology
      techniques are currently used for a rapid detection of these pathogens and the
      adoption of control measures of the diseases. The aim of this study was to
      develop and validate a technique for simultaneous detection of MG and MS by
      multiplex real time polymerase chain reaction (PCR). The complete assay
      (Multiplex MGMS) was designed with primers and probes specific for each pathogen
      and developed to be carried out in a single tube reaction. Vaccines, MG and MS
      isolates and DNA from other Mycoplasma species were used for the development and
      validation of the method. Further, 78 pooled clinical samples from different
      poultry flocks in Brazil were obtained and used to determine the sensitivity and
      specificity of the technique in comparison to 2 real time PCR assays specific for
      MG (MG PCR) and MS (MS PCR). The results demonstrated an agreement of 100% (23
      positive and 44 negative samples) between Multiplex MGMS and MG PCR in the
      analysis of 67 samples from MG positive and negative poultry flocks, and an
      agreement of 96.9% between Multiplex MGMS and MS PCR in the analysis of 64
      samples from MS positive and negative poultry flocks. Considering the single
      amplification tests as the gold standard, the Multiplex MGMS showed 100% of
      specificity and sensitivity in the MG analysis and 94.7% sensitivity and 100%
      specificity in the MS analysis. This new assay could be used for rapid analysis
      of MG and MS in the poultry industry laboratories. 

PMID- 24294248
TI  - Bovine response to lipoarabinomannan vaccination and challenge with Mycobacterium
      paratuberculosis.
AB  - This study aimed to evaluate the immune response in bovines following
      immunization with a mycobaterial Lipoarabinomannan extract (LAMe) and the effect
      of Map challenge. LAMe vaccine induced specific antibody levels that diminished
      after the challenge and affected Map excretion at least for 100 days thereafter. 

PMID- 24294249
TI  - Prevalence of the paa gene (porcine attaching and effacing associated) in porcine
      enteropathogenic Escherichia coli (PEPEC) associated with postweaning diarrhea in
      south Brazil.
AB  - Paa (porcine attaching and effacing associated) may be an important virulence
      factor E. coli of piglets with diarrhea. This study showed for the first time in
      Brazil the prevalence of the paa gene (22%) in E. coli strains isolated from
      piglets and these isolates also harboured genes for other adhesins and toxins LT
      II, STa and STb. 

PMID- 24294250
TI  - Immunologic cross-reactivity between Muscovy duck parvovirus and goose parvovirus
      on the basis of epitope prediction.
AB  - Through bioinformatic prediction, between Muscovy duck parvovirus (MDPV) and
      goose parvovirus (GPV), there were one epitope AA503-509 (RANEPKE) on non
      structural protein and three epitopes AA426-430 (SQDLD), 540-544 (DPYRS), 685-691
      (KENSKRW) on structural protein might cross-react with each other. Furthermore,
      the four epitops were expressed in Escherichia coli. All the four recombinant
      proteins could react with GPV-antisera and MDPV-antisera in Western blot. 

PMID- 24294251
TI  - Bacterial consortium for copper extraction from sulphide ore consisting mainly of
      chalcopyrite.
AB  - The mining industry is looking forward for bacterial consortia for economic
      extraction of copper from low-grade ores. The main objective was to determine an
      optimal bacterial consortium from several bacterial strains to obtain copper from
      the leach of chalcopyrite. The major native bacterial species involved in the
      bioleaching of sulphide ore (Acidithiobacillus ferrooxidans, Acidithiobacillus
      thiooxidans, Leptospirillum ferrooxidans and Leptospirillum ferriphilum) were
      isolated and the assays were performed with individual bacteria and in
      combination with At. thiooxidans. In conclusion, it was found that the consortium
      integrated by At. ferrooxidans and At. thiooxidans removed 70% of copper in 35
      days from the selected ore, showing significant differences with the other
      consortia, which removed only 35% of copper in 35 days. To validate the assays
      was done an escalation in columns, where the bacterial consortium achieved a
      higher percentage of copper extraction regarding to control. 

PMID- 24294252
TI  - Optimization and characterization of alkaline protease and carboxymethyl
      cellulase produced by Bacillus pumillus grown on Ficus nitida wastes.
AB  - The potentiality of 23 bacterial isolates to produce alkaline protease and
      carboxymethyl-cellulase (CMCase) on Ficus nitida wastes was investigated.
      Bacillus pumillus ATCC7061 was selected as the most potent bacterial strain for
      the production of both enzymes. It was found that the optimum production of
      protease and CMCase were recorded at 30  degrees C, 5% Ficus nitida leaves and
      incubation period of 72 h. The best nitrogen sources for protease and CMCase
      production were yeast extract and casein, respectively. Also maximum protease and
      CMCase production were reported at pH 9 and pH 10, respectively. The enzymes
      possessed a good stability over a pH range of 8-10, expressed their maximum
      activities at pH10 and temperature range of 30-50  degrees C, expressed their
      maximum activities at 50  degrees C. Ions of Hg(2+), Fe2+ and Ag(+) showed a
      stimulatory effect on protease activity and ions of Fe(2+), Mg(2+), Ca(2+),
      Cu(2+) and Ag(+) caused enhancement of CMCase activity. The enzymes were stable
      not only towards the nonionic surfactants like Triton X-100 and Tween 80 but also
      the strong anionic surfactant, SDS. Moreover, the enzymes were not significantly
      inhibited by EDTA or cystein. Concerning biotechnological applications, the
      enzymes retained (51-97%) of their initial activities upon incubation in the
      presence of commercials detergents for 1 h. The potential use of the produced
      enzymes in the degradation of human hair and cotton fabric samples were also
      assessed. 

PMID- 24294253
TI  - Semi-scale production of PHAs from waste frying oil by Pseudomonas fluorescens
      S48.
AB  - The present study aimed at developing a strategy to improve the volumetric
      production of PHAs by Pseudomonas fluorescens S48 using waste frying oil (WFO) as
      the sole carbon source. For this purpose, several cultivations were set up to
      steadily improve nutrients supply to attain high cell density and high biopolymer
      productivity. The production of PHAs was examined in a 14 L bioreactor as one
      stage batch, two-stage batch, and high-cell-density fed-batch cultures. The
      highest value of polymer content in one-stage bioreactor was obtained after 60 h
      (33.7%). Whereas, the two-stage batch culture increased the polymer content to
      50.1% after 54 h. High-cell-density (0.64 g/L) at continuous feeding rate 0.55
      mL/l/h of WFO recorded the highest polymer content after 54 h (55.34%). Semi
      scale application (10 L working volume) increased the polymer content in one
      stage batch, two-stage batch and high cell density fed-batch cultures by about
      12.3%, 5.8% and 11.3%, respectively, as compared with that obtained in 2 L
      fermentation culture. Six different methods for biopolymer extraction were done
      to investigate their efficiency for optimum polymer recovery. The maximum
      efficiency of solvent recovery of PHA was attained by chloroform-hypochlorite
      dispersion extraction. Gas chromatography (GC) analysis of biopolymer produced by
      Pseudomonas fluorescens S48 indicated that it solely composed of 3-hydrobutyric
      acid (98.7%). A bioplastic film was prepared from the obtained PHB. The isolate
      studied shares the same identical sequence, which is nearly the complete 16S rRNA
      gene. The identity of this sequence to the closest pseudomonads strains is about
      98-99%. It was probably closely related to support another meaningful parsiomony
      analysis and construction of a phylogenetic tree. The isolate is so close to
      Egyptian strain named EG 639838. 

PMID- 24294254
TI  - Yeast biomass production: a new approach in glucose-limited feeding strategy.
AB  - The aim of this work was to implement experimentally a simple glucose-limited
      feeding strategy for yeast biomass production in a bubble column reactor based on
      a spreadsheet simulator suitable for industrial application. In biomass
      production process using Saccharomyces cerevisiae strains, one of the constraints
      is the strong tendency of these species to metabolize sugars anaerobically due to
      catabolite repression, leading to low values of biomass yield on substrate. The
      usual strategy to control this metabolic tendency is the use of a fed-batch
      process in which where the sugar source is fed incrementally and total sugar
      concentration in broth is maintained below a determined value. The simulator
      presented in this work was developed to control molasses feeding on the basis of
      a simple theoretical model in which has taken into account the nutritional growth
      needs of yeast cell and two input data: the theoretical specific growth rate and
      initial cell biomass. In experimental assay, a commercial baker's yeast strain
      and molasses as sugar source were used. Experimental results showed an overall
      biomass yield on substrate of 0.33, a biomass increase of 6.4 fold and a specific
      growth rate of 0.165 h(-1) in contrast to the predicted value of 0.180 h-1 in the
      second stage simulation. 

PMID- 24294255
TI  - Some factors affecting tannase production by Aspergillus niger Van Tieghem.
AB  - One variable at a time procedure was used to evaluate the effect of qualitative
      variables on the production of tannase from Aspergillus niger Van Tieghem. These
      variables including: fermentation technique, agitation condition, tannins source,
      adding carbohydrates incorporation with tannic acid, nitrogen source type and
      divalent cations. Submerged fermentation under intermittent shaking gave the
      highest total tannase activity. Maximum extracellular tannase activity (305
      units/50 mL) was attained in medium containing tannic acid as tannins source and
      sodium nitrate as nitrogen source at 30  degrees C for 96 h. All added
      carbohydrates showed significant adverse effects on the production of tannase.
      All tested divalent cations significantly decreased tannase production. Moreover,
      split plot design was carried out to study the effect of fermentation temperature
      and fermentation time on tannase production. The results indicated maximum
      tannase production (312.7 units/50 mL) at 35  degrees C for 96 h. In other words,
      increasing fermentation temperature from 30  degrees C to 35  degrees C resulted
      in increasing tannase production. 

PMID- 24294256
TI  - Efficient production of lignocellulolytic enzymes xylanase, beta-xylosidase,
      ferulic acid esterase and beta-glucosidase by the mutant strain Aspergillus
      awamori 2B.361 U2/1.
AB  - The production of xylanase, beta-xylosidase, ferulic acid esterase and beta
      glucosidase by Aspergillus awamori 2B.361 U2/1, a hyper producer of glucoamylase
      and pectinase, was evaluated using selected conditions regarding nitrogen
      nutrition. Submerged cultivations were carried out at 30  degrees C and 200 rpm
      in growth media containing 30 g wheat bran/L as main carbon source and either
      yeast extract, ammonium sulfate, sodium nitrate or urea, as nitrogen sources; in
      all cases it was used a fixed molar carbon to molar nitrogen concentration of
      10.3. The use of poor nitrogen sources favored the accumulation of xylanase, beta
      xylosidase and ferulic acid esterase to a peak concentrations of 44,880; 640 and
      118 U/L, respectively, for sodium nitrate and of 34,580, 685 and 170 U/L,
      respectively, for urea. However, the highest beta-glucosidase accumulation of
      10,470 U/L was observed when the rich organic nitrogen source yeast extract was
      used. The maxima accumulation of filter paper activity, xylanase, beta
      xylosidase, ferulic acid esterase and beta-glucosidase by A. awamori 2B.361 U2/1
      was compared to that produced by Trichoderma reesei Rut-C30. The level of beta
      glucosidase was over 17-fold higher for the Aspergillus strain, whereas the
      levels of xylanase and beta-xylosidase were over 2-fold higher. This strain also
      produced ferulic acid esterase (170 U/L), which was not detected in the T. reesei
      culture. 

PMID- 24294257
TI  - Chemical and botanical characterization of Chilean propolis and biological
      activity on cariogenic bacteria Streptococcus mutans and Streptococcus sobrinus.
AB  - Propolis is a non-toxic natural substance with multiple pharmacological
      properties including anti-cancer, antioxidant, fungicidal, antibacterial,
      antiviral, and anti-inflammatory among others. The aim of this study was to
      determine the chemical and botanical characterization of Chilean propolis samples
      and to evaluate their biological activity against the cariogenic bacteria
      Streptococcus mutans and Streptococcus sobrinus. Twenty propolis samples were
      obtained from beekeeping producers from the central and southern regions of
      Chile. The botanical profile was determined by palynological analysis. Total
      phenolic contents were determined using colorimetric assays. Reverse phase HPLC
      and HPLC-MS were used to determine the chemical composition. The minimum
      inhibitory concentration (MIC) was determined on S. mutans and S. sobrinus. All
      propolis samples were dominated by structures from native plant species. The
      characterization by HPLC/MS, evidenced the presence of quercetin, myricetin,
      kaempferol, rutine, pinocembrin, coumaric acid, caffeic acid and caffeic acid
      phenethyl ester, that have already been described in these propolis with
      conventional HPLC. Although all propolis samples inhibited the mutans
      streptococci growth, it was observed a wide spectrum of action (MIC 0.90 to 8.22
      MUg mL(-1)). Given that results it becomes increasingly evident the need of
      standardization procedures, where we combine both the determination of botanical
      and the chemical characterization of the extracts. Research conducted to date,
      describes a promising effectiveness of propolis in the prevention of caries and
      other diseases of the oral cavity, making it necessary to develop studies to
      identify and understand the therapeutic targets or mechanisms of molecular action
      of the various compounds present on them. 

PMID- 24294258
TI  - Screening of efficient arbuscular mycorrhizal fungi for Azadirachta indica under
      nursery condition: a step towards afforestation of semi-arid region of western
      India.
AB  - To optimize nursery practices for efficient plant production procedures and to
      keep up to the ever growing demand of seedlings, identification of the most
      suitable species of arbuscular mycorrhizal fungi (AMF), specific for a given tree
      species, is clearly a necessary task. Sixty days old seedlings of Neem
      (Azadirachta indica A. Juss) raised in root trainers were inoculated with six
      species of AMF and a mixed inoculum (consortia) and kept in green house.
      Performances of the treatments on this tree species were evaluated in terms of
      growth parameters like plant height shoot collar diameter, biomass and
      phosphorous uptake capabilities. Significant and varied increase in the growth
      parameters and phosphorous uptake was observed for most of the AMF species
      against control. Consortia culture was found to be the best suited AMF treatment
      for A. indica, while Glomus intraradices and Glomus mosseae were the best
      performing single species cultures. It is the first time in the state of Gujarat
      that a wide variety of AMF species, isolated from the typical semi-arid region of
      western India, were tested for the best growth performance with one of the most
      important tree species for the concerned region. 

PMID- 24294259
TI  - In situ biosurfactant production and hydrocarbon removal by Pseudomonas putida CB
      100 in bioaugmented and biostimulated oil-contaminated soil.
AB  - In situ biosurfactant (rhamnolipid) production by Pseudomonas putida CB-100 was
      achieved during a bioaugmented and biostimulated treatment to remove hydrocarbons
      from aged contaminated soil from oil well drilling operations. Rhamnolipid
      production and contaminant removal were determined for several treatments of
      irradiated and non-irradiated soils: nutrient addition (nitrogen and phosphorus),
      P. putida addition, and addition of both (P. putida and nutrients). The results
      were compared against a control treatment that consisted of adding only
      sterilized water to the soils. In treatment with native microorganisms (non
      irradiated soils) supplemented with P. putida, the removal of total petroleum
      hydrocarbons (TPH) was 40.6%, the rhamnolipid production was 1.54 mg/kg, and a
      surface tension of 64 mN/m was observed as well as a negative correlation (R = 
      0.54; p < 0.019) between TPH concentration (mg/kg) and surface tension (mN/m),
      When both bacteria and nutrients were involved, TPH levels were lowered to 33.7%,
      and biosurfactant production and surface tension were 2.03 mg/kg and 67.3 mN/m,
      respectively. In irradiated soil treated with P. putida, TPH removal was 24.5%
      with rhamnolipid generation of 1.79 mg/kg and 65.6 mN/m of surface tension, and a
      correlation between bacterial growth and biosurfactant production (R = -0.64; p <
      0.009) was observed. When the nutrients and P. putida were added, TPH removal was
      61.1%, 1.85 mg/kg of biosurfactants were produced, and the surface tension was
      55.6 mN/m. In summary, in irradiated and non-irradiated soils, in situ
      rhamnolipid production by P. putida enhanced TPH decontamination of the soil. 

PMID- 24294260
TI  - Epicoccum nigrum and Cladosporium sp. for the treatment of oily effluent in an
      air-lift reactor.
AB  - The metalworking industry is responsible for one of the most complex and
      difficult to handle oily effluents. These effluents consist of cutting fluids,
      which provide refrigeration and purification of metallic pieces in the machining
      system. When these effluents are biologically treated, is important to do this
      with autochthonous microorganisms; the use of these microorganisms
      (bioaugmentation) tends to be more efficient because they are already adapted to
      the existing pollutants. For this purpose, this study aimed to use two indigenous
      microorganisms, Epicoccum nigrum and Cladosporium sp. for metalworking effluent
      treatment using an air-lift reactor; the fungus Aspergillus niger (laboratory
      strain) was used as a reference microorganism. The original effluent
      characterization presented considerable pollutant potential. The color of the
      effluent was 1495 mg Pt/L, and it contained 59 mg/L H2O2, 53 mg/L total phenols,
      2.5 mgO2/L dissolved oxygen (DO), and 887 mg/L oil and grease. The COD was 9147
      mgO2/L and the chronic toxicity factor was 1667. Following biotreatment, the
      fungus Epicoccum nigrum was found to be the most efficient in reducing (effective
      reduction) the majority of the parameters (26% COD, 12% H2O2, 59% total phenols,
      and 40% oil and grease), while Cladosporium sp. was more efficient in color
      reduction (77%). 

PMID- 24294261
TI  - Copper resistance of different ectomycorrhizal fungi such as Pisolithus
      microcarpus, Pisolithus sp., Scleroderma sp. and Suillus sp.
AB  - Environments contaminated with heavy metals negatively impact the living
      organisms. Ectomycorrhizal fungi have shown important role in these impacted
      sites. Thus, this study aimed to evaluate the copper-resistance of
      ectomycorrhizal fungi isolates Pisolithus microcarpus - UFSC-Pt116; Pisolithus
      sp. - UFSC-PT24, Suillus sp. - UFSM RA 2.8 and Scleroderma sp. - UFSC-Sc124 to
      different copper doses in solid and liquid media. The copper doses tested were:
      0.00, 0.25, 0.5, 0.75, 1.0 and 1.25 mmol L(-1) in the solid medium and 0.00,
      0.32, 0.64 and 0.96 mmol L(-1) in the liquid medium. Copper was amended as copper
      sulphate in order to supplement the culture medium MNM at pH 4.8, with seven
      replicates to each fungus-dose combination. The fungal isolates were incubated
      for 30 days at 28  degrees C. UFSC-Pt116 showed high copper-resistance such as
      accessed by CL50 determinations (concentration to reduce 50% of the growth) as
      while as UFSC-PT24 displayed copper-resistance mechanism at 0.50 mmol L(-1) in
      solid medium. The UFSC-PT24 and UFSC-Sc124 isolates have increased copper
      resistance in liquid medium. The higher production of extracellular pigment was
      detected in UFSC-Pt116 cultures. The UFSC-Pt116 and UFSC-PT24 isolates showed
      higher resistance for copper and produced higher mycelium biomass than the other
      isolates. In this way, the isolates UFSG-Pt116 and UFSC-PT24 can be important
      candidates to survive in copper-contaminated areas, and can show important role
      in plants symbiosis in these contaminated sites. 

PMID- 24294262
TI  - Colonization and plant growth promoting characterization of endophytic
      Pseudomonas chlororaphis strain Zong1 isolated from Sophora alopecuroides root
      nodules.
AB  - The endophytic strain Zong1 isolated from root nodules of the legume Sophora
      alopecuroides was characterized by conducting physiological and biochemical tests
      employing gfp-marking, observing their plant growth promoting characteristics
      (PGPC) and detecting plant growth parameters of inoculation assays under
      greenhouse conditions. Results showed that strain Zong1 had an effective growth
      at 28 oC after placed at 4-60 oC for 15 min, had a wide range pH tolerance of 6.0
      11.0 and salt tolerance up to 5% of NaCl. Zong1 was resistant to the following
      antibiotics (MUg/mL): Phosphonomycin (100), Penicillin (100) and Ampicillin
      (100). It could grow in the medium supplemented with 1.2 mmol/L Cu, 0.1% (w/v)
      methylene blue and 0.1-0.2% (w/v) methyl red, respectively. Zong1 is closely
      related to Pseudomonas chlororaphis based on analysis the sequence of 16S rRNA
      gene. Its expression of the gfp gene indicated that strain Zong1 may colonize in
      root or root nodules and verified by microscopic observation. Furthermore, co
      inoculation with Zong1 and SQ1 (Mesorhizobium sp.) showed significant effects
      compared to single inoculation for the following PGPC parameters: siderophore
      production, phosphate solubilization, organic acid production, IAA production and
      antifungal activity in vitro. These results suggest strains P. chlororaphi Zong1
      and Mesorhizobium sp. SQ1 have better synergistic or addictive effect. It was
      noteworthy that each growth index of co-inoculated Zong1+SQ1 in growth assays
      under greenhouse conditions is higher than those of single inoculation, and
      showed a significant difference (p < 0.05) when compared to a negative control.
      Therefore, as an endophyte P. chlororaphis Zong1 may play important roles as a
      potential plant-growth promoting agent. 

PMID- 24294263
TI  - Transcriptional profiling of genes involved in n-hexadecane compounds
      assimilation in the hydrocarbon degrading Dietzia cinnamea P4 strain.
AB  - The petroleum-derived degrading Dietzia cinnamea strain P4 recently had its
      genome sequenced and annotated. This allowed employing the data on genes that are
      involved in the degradation of n-alkanes. To examine the physiological behavior
      of strain P4 in the presence of n-alkanes, the strain was grown under varying
      conditions of pH and temperature. D. cinnamea P4 was able to grow at pH 7.0-9.0
      and at temperatures ranging from 35 oC to 45 oC. Experiments of gene expression
      by real-time quantitative RT-PCR throughout the complete growth cycle clearly
      indicated the induction of the regulatory gene alkU (TetR family) during early
      growth. During the logarithmic phase, a large increase in transcriptional levels
      of a lipid transporter gene was noted. Also, the expression of a gene that
      encodes the protein fused rubredoxin-alkane monooxygenase was enhanced. Both
      genes are probably under the influence of the AlkU regulator. 

PMID- 24294264
TI  - The potential effects of Zataria multiflora Boiss essential oil on growth,
      aflatoxin production and transcription of aflatoxin biosynthesis pathway genes of
      toxigenic Aspergillus parasiticus.
AB  - This study aims at evaluating the effects of Zataria multiflora (Z. multiflora)
      essential oil (EO) on growth, aflatoxin production and transcription of aflatoxin
      biosynthesis pathway genes. Total RNAs of Aspergillus parasiticus (A.parasiticus)
      ATCC56775 grown in yeast extract sucrose (YES) broth medium treated with Z.
      multiflora EO were subjected to reverse transcription- polymerase chain reaction
      (RT-PCR). Specific primers of nor-1, ver-1, omt-A and aflR genes were used. In
      parallel mycelial dry weight of samples were measured and all the media were
      assayed by high-pressure liquid chromatography (HPLC) for aflatoxinB1 (AFB1),
      aflatoxinB2 (AFB2), aflatoxinG1 (AFG1), aflatoxinG2 (AFG2) and aflatoxin total
      (AFTotal) production. The results showed that mycelial dry weight and aflatoxin
      production reduce in the presence of Z. multiflora EO (100 ppm) on day 5 of
      growth. It was found that the expression of nor-1, ver-1, omt-A and aflR genes
      was correlated with the ability of fungus to produce aflatoxins on day 5 in YES
      medium. RT-PCR showed that in the presence of Z.multiflora EO (100 ppm) nor-1,
      ver-1 and omtA genes expression was reduced. It seems that toxin production
      inhibitory effects of Z. multiflora EO on day 5 may be at the transcription level
      and this herb may cause reduction in aflatoxin biosynthesis pathway genes
      activity. 

PMID- 24294265
TI  - Plasmid-mediated quinolone resistance (PMQR) and mutations in the topoisomerase
      genes of Salmonella enterica strains from Brazil.
AB  - The objective of this study was to identify mutations in the Quinolone Resistance
      Determining sources Regions (QRDR) of the gyrA, gyrB, parC, and parE genes and to
      determine if any of the qnr variants or the aac(6')-Ib-cr variant were present in
      strains of Salmonella spp. isolated in Brazil. A total of 126 Salmonella spp.
      strains from epidemic (n = 114) and poultry (n = 12) origin were evaluated. One
      hundred and twelve strains (88.8%) were resistant to nalidixic acid (NAL) and 29
      (23.01%) showed a reduced susceptibility to ciprofloxacin (Cip). The mutations
      identified were substitutions limited to the QRDR of the gyrA gene in the codons
      for Serine 83, Aspartate 87 and Alanine 131. The sensitivity to NAL seems to be a
      good phenotypic indication of distinguishing mutated and non-mutated strains in
      the QRDR, however the double mutation in gyrA did not cause resistance to
      ciprofloxacin. The qnrA1 and qnrB19 genes were detected, respectively, in one
      epidemic strain of S. Enteritidis and one strain of S. Corvallis of poultry
      origin. Despite previous detection of qnr genes in Brazil, this is the first
      report of qnr gene detection in Salmonella, and also the first detection of
      qnrB19 gene in this country. The results alert for the continuous monitoring of
      quinolone resistance determinants in order to minimize the emergence and
      selection of Salmonella spp. strains showing reduced susceptibility or resistance
      to quinolones. 

PMID- 24294267
TI  - Mechanistic understanding of the effect of obesity on asthma and allergy.

PMID- 24294266
TI  - Molecular approach to characterize ectomycorrhizae fungi from Mediterranean pine
      stands in Portugal.
AB  - Stone pine (Pinus pinea L.), like other conifers, forms ectomycorrhizas (ECM),
      which have beneficial impact on plant growth in natural environments and forest
      ecosystems. An in vitro co-culture of stone pine microshoots with pure mycelia of
      isolated ECM sporocarps was used to overcome the root growth cessation not only
      in vitro but also to improve root development during acclimation phase.
      Pisolithus arhizus (Scop.) Rauschert and Lactarius deliciosus (L. ex Fr.) S.F.
      Gray fungi, were collected, pure cultured and used in in vitro co-culture with
      stone pine microshoots. Samples of P. arhizus and L. deliciosus for the in vitro
      co-cultures were collected from the pine stands southwest Portugal. The in situ
      characterization was based on their morphotypes. To confirm the identity of the
      collected material, ITS amplification was applied using the pure cultures derived
      from the sporocarps. Additionally, a molecular profile using PCR based genomic
      fingerprinting comparison was executed with other genera of Basidiomycetes and
      Ascomycetes. Our results showed the effectiveness of the techniques used to
      amplify DNA polymorphic sequences, which enhances the characterization of the
      genetic profile of ECM fungi and also provides an option to verify the fungus
      identity at any stage of plant mycorrhization. 

PMID- 24294268
TI  - A review of 11 years of Stenotrophomonas maltophilia blood isolates at a tertiary
      care institute in Canada.
AB  - BACKGROUND: Stenotrophomonas maltophilia has emerged as a significant nosocomial
      pathogen with increasing resistance to trimethoprim/sulphamethoxazole (TMP/SMX),
      the current drug of choice for treatment. OBJECTIVES: To describe the
      microbiological and clinical characteristics of S maltophilia bloodstream
      infections (BSIs) over an 11-year period at a tertiary care centre in Canada.
      METHODS: All adult S maltophilia BSIs from 1999 to 2009 in a 750-bed tertiary
      care teaching hospital (University of Alberta Hospital, Edmonton, Alberta) were
      identified through the infection control nosocomial infection surveillance
      program. Demographic and clinical data were extracted from the infection control
      database and from patient charts. Microbiological data were confirmed through the
      laboratory information system. RESULTS: Twenty-five episodes of S maltophilia BSI
      (0.9% of all BSIs) involving 24 patients were identified between 1999 and 2009.
      The patient age range was 18 to 83 years (average 45.7 years). The majority were
      men (14 of 24 [58.3%]). The mean length of hospital stay was 83.3 days (range
      eight to 310 days). The rate of S maltophilia BSIs per 1000 admissions ranged
      from 0.04 to 0.22 (average 0.09). Greater than one-half of the episodes (13 of 25
      [52%]) were admitted to the intensive care unit before BSI onset. Laboratory data
      were available for 24 of the 25 isolates. Polymicrobial infections were present
      in 11 of 24 (45.8%) patients. Resistance to TMP/SMX occurred in 8.3% of all
      infections. Fifteen per cent of isolates were resistant to
      ticarcillin/clavulanate. Mortality attributed to bacteremia was 16.7%.
      CONCLUSIONS: In the University of Alberta Hospital, the rate of S maltophilia BSI
      remains low and constant, and TMP/SMX remains the drug of choice for treatment.

PMID- 24294269
TI  - Community-onset bloodstream infection during the 'after hours' is not associated
      with an increased risk for death.
AB  - BACKGROUND/OBJECTIVE: Patients admitted to hospital during the 'after hours'
      (weekends and evenings) may be at increased risk for adverse outcome. The
      objective of the present study was to assess whether community-onset bloodstream
      infections presenting in the after hours are associated with death. METHODS: All
      patients in the Victoria area of British Columbia, who had first admissions with
      community-onset bloodstream infections between 1998 and 2005 were included. The
      day of admission to hospital, the day and time of culture draw, and all-cause, in
      hospital mortality were ascertained. RESULTS: A total of 2108 patients were
      studied. Twenty-six per cent of patients were admitted on a weekend. Blood
      cultures were drawn on a weekend in 27% of cases and, in 43%, 33%, and 25% of
      cases, cultures were drawn during the day (08:00 to 17:59), the evening (18:00 to
      22:59) and night (23:00 to 07:59), respectively. More than two-thirds (69%) of
      index cultures were drawn during the after hours (any time Saturday or Sunday and
      weekdays 18:00 to 07:59). The overall in-hospital case fatality rate was 13%. No
      difference in mortality was observed in relation to the day of the week of
      admission or time period of sampling. After-hours sampling was not associated
      with mortality in a multivariable logistic regression model examining factors
      associated with death. CONCLUSION: Presentation with community-onset, bloodstream
      infection during the after hours does not increase the risk of death.

PMID- 24294270
TI  - Tuberculosis in the intensive care unit: A retrospective descriptive cohort study
      with determination of a predictive fatality score.
AB  - BACKGROUND: Despite effective treatments, tuberculosis-related mortality remains
      high among patients requiring admission to the intensive care unit (ICU).
      OBJECTIVE: To determine prognostic factors of death in tuberculosis patients
      admitted to the ICU, and to develop a simple predictive scoring system. METHODS:
      A 10-year, retrospective study of 53 patients admitted consecutively to the
      Hopitaux de Paris, Hopital Lariboisiere (Paris, France) ICU with confirmed
      tuberculosis, was conducted. A multivariate analysis was performed to identify
      risk factors for death. A predictive fatality score was determined. RESULTS:
      Diagnoses included pulmonary tuberculosis (96%) and tuberculous
      encephalomeningitis (26%). Patients required mechanical ventilation (45%) and
      vasopressor infusion (28%) on admission. Twenty patients (38%) died, related to
      direct tuberculosis-induced organ failure (n=5), pulmonary bacterial coinfections
      (n=14) and pulmonary embolism (n=1). Using a multivariate analysis, three
      independent factors on ICU admission were predictive of fatality: miliary
      pulmonary tuberculosis (OR 9.04 [95% CI 1.25 to 65.30]), mechanical ventilation
      (OR 11.36 [95% CI 1.55 to 83.48]) and vasopressor requirement (OR 8.45 [95% CI
      1.29 to 55.18]). A score generated by summing these three independent variables
      was effective at predicting fatality with an area under the ROC curve of 0.92
      (95% CI 0.85 to 0.98). CONCLUSIONS: Fatalities remain high in patients admitted
      to the ICU with tuberculosis. Miliary pulmonary tuberculosis, mechanical
      ventilation and vasopressor requirement on admission were predictive of death.

PMID- 24294271
TI  - Breakthrough filamentous fungal infections in pediatric hematopoetic stem cell
      transplant and oncology patients receiving caspofungin.
AB  - BACKGROUND: Caspofungin is an echinocandin class antifungal medication that is
      commonly used empirically in immunocompromised patients at high risk for invasive
      fungal disease. OBJECTIVE: To describe the clinical characteristics of
      breakthrough fungal infections in pediatric hematopoetic stem cell transplant
      recipients, and oncology and hematology patients receiving caspofungin. METHODS:
      A five-year retrospective review, from 2004 through 2008, of all cases of proven
      invasive filamentous fungal infection of children admitted to The Hospital for
      Sick Children (Toronto, Ontario) was conducted. A breakthrough infection was
      defined as new onset of symptoms that were later proven to be due to an invasive
      mold infection on day 3 or later after initiation of caspofungin therapy.
      RESULTS: Six confirmed positive cultures (Aspergillus fumigatus [two cases],
      Aspergillus niger, Fusarium oxysporum, Alternaria infectoria and Rhizomucor
      pusillus) met the criteria for breakthrough filamentous mold infection while on
      caspofungin therapy. Underlying immunocompromising conditions included acute
      lymphoblastic leukemia (two cases), acute myeloid leukemia (two cases), Burkitt's
      lymphoma and aplastic anemia. Four of the patients underwent a hematopoetic stem
      cell transplant. All patients received a lipid amphotericin B product as part of
      their treatment for breakthrough infection. Five patients also received
      voriconazole and one received posaconazole. Four of the six patients died and two
      responded with a clinical and microbiological cure. DISCUSSION: There are few
      descriptions of breakthrough fungal infections in pediatric patients receiving
      caspofungin. The six cases presented here, all microbiologically proven, are
      likely only a fraction of the total number of possible breakthrough invasive
      fungal infections that occured over the study period. CONCLUSION: Clinicians must
      remain aware that breakthrough fungal infections by species not covered by
      particular antifungals, including caspofungin, do occur and may have poor
      outcomes.

PMID- 24294272
TI  - Application and interpretation of an interferon-gamma release assay: Results of
      an audit in a Canadian centre.
AB  - BACKGROUND: Interferon-gamma release assays (IGRAs) are newly approved for
      diagnosing latent tuberculosis infection (LTBI). An internal audit was conducted
      to review the use of a newly implemented IGRA at the Hopital du Sacre-Coeur de
      Montreal (Montreal, Quebec) to evaluate its concordance with Canadian
      recommendations and its implication on diagnosis. METHODS: From April 2007 to
      January 2009, all Quantiferon TB Gold In-Tube (QFT, Cellestis inc, USA) tests
      performed in at the Hopital du Sacre-Coeur de Montreal were retrieved. Strategies
      used to investigate LTBI and clinical interpretation of test results were
      compared with the local algorithm, which is derived from the current national
      guidelines. RESULTS: A total of 200 patients tested with QFT were included in the
      analysis. LTBI investigation and QFT testing were considered to be appropriate in
      87.5% and 66.5% of patients, respectively. Overall, 67 QFT tests were performed
      inappropriately; 25 were performed when a LTBI investigation was not indicated
      and 42 were performed whe LTBI interpretation was possible with the result of the
      tuberculin skin test alone. Among the 175 patients investigated appropriately for
      LTBI, 49 QFT tests (28%) were interpreted incorrectly; 32 patients (at high risk
      of developing active tuberculosis) had a positive tuberculin skin test and a
      negative QFT result wrongly interpreted as being negative for LTBI and 13
      patients should have undergone further LTBI investigations. CONCLUSION: Globally,
      the present study revealed that there are discrepancies on how the IGRA was
      employed and interpreted in a Montreal hospital and that strict compliance to the
      guidelines could significantly reduce errors in interpretation.

PMID- 24294273
TI  - Cost comparison of linezolid versus vancomycin for treatment of complicated skin
      and skin-structure infection caused by methicillin-resistant Staphylococcus
      aureus in Quebec.
AB  - BACKGROUND: In Canada, complicated skin and skin-structure infection (cSSSI)
      caused by methicillin-resistant Staphylococcus aureus (MRSA) is usually treated
      with antibiotics in hospital, with a follow-up course at home for stable
      patients. The cost implications of using intravenous and oral linezolid instead
      of intravenous vancomycin in Canadian clinical practice have not been examined.
      OBJECTIVES: To evaluate the potential treatment cost impact for the Quebec health
      care system of linezolid versus vancomycin for MRSA-related cSSSI therapy, using
      a net impact analysis approach. METHODS: Health care resource use associated with
      linezolid and vancomycin therapy was estimated for patients in Quebec, based on
      expert opinion. Costs were assigned to health care resources (antibiotics,
      medical supplies, laboratory testing and health care professional time) based on
      unit prices. The base-case analysis assumed 14 days of antibiotic treatment for
      both agents; five days in hospital followed by nine days at home. Therapy
      duration, length of inpatient treatment and discharge rates were varied in
      sensitivity analyses. RESULTS: Antibiotic costs were higher for linezolid than
      for vancomycin, for both inpatient ($874 versus $144, respectively) and
      outpatient therapy ($1,356 versus $1,242, respectively). Compared with
      vancomycin, lower costs for antibiotic preparation, administration and monitoring
      of linezolid offset drug acquisition costs. Total treatment costs were $3,850 for
      linezolid versus $5,189 for vancomycin. Results were sensitive to the number of
      treatment days spent at home and the discharge rate. CONCLUSION: Using linezolid
      instead of vancomycin to treat MRSA-related cSSSI, for hospital and home courses
      combined, may reduce health care resource utilization and costs in Quebec.

PMID- 24294274
TI  - Penicillin susceptibility and macrolide-lincosamide-streptogramin B resistance in
      group B Streptococcus isolates from a Canadian hospital.
AB  - BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) is recommended for pregnant
      women who test positive for group B Streptococcus (GBS) in their genitourinary
      tract to prevent GBS-induced neonatal sepsis. Penicillin G is used as the primary
      antibiotic, and clindamycin or erythromycin as the secondary, if allergies exist.
      Decreased susceptibility to penicillin G has occasionally been reported; however,
      clindamycin and erythromycin resistance is on the rise and is causing concern
      over the use of clindamycin and erythromycin IAP. METHODS: Antibiotic resistance
      was characterized phenotypically using a D-Test for erythromycin and clindamycin,
      while an E-Test (E-strip) was used for penicillin G. GBS was isolated from
      vaginal-rectal swabs and serologically confirmed using Prolex (Pro-Lab
      Diagnostics, Canada) streptococcal grouping reagents. Susceptibility testing of
      isolates was performed according to the Clinical Laboratory Standards Institute
      guidelines. RESULTS: All 158 isolates were penicillin G sensitive. Inducible
      macrolide-lincosamide-streptogramin B (MLSB) resistance was observed in 13.9% of
      isolates. Constitutive MLSB resistance was observed in 12.7% of isolates. M
      phenotype resistance was observed in 6.3% of isolates. In total, erythromycin
      resistance was present in 32.9% of the GBS isolates, while clindamycin resistance
      was present in 26.6%. DISCUSSION: The sampled GBS population showed no sign of
      reduced penicillin susceptibility, with all being well under susceptible minimum
      inhibitory concentration values. These data are congruent with the large body of
      evidence showing that penicillin G remains the most reliable clinical antibiotic
      for IAP. Clindamycin and erythromycin resistance was higher than expected,
      contributing to a growing body of evidence that suggests the re-evaluation of
      clindamycin and erythromycin IAP is warranted.

PMID- 24294275
TI  - Risk factors and outcomes for pandemic H1N1 influenza compared with seasonal
      influenza in hospitalized children in China.
AB  - OBJECTIVE: To compare clinical features and outcomes of children hospitalized in
      China with pandemic (p)H1N1 between 2009 and 2010 versus seasonal influenza A
      between 2008 and 2009. METHODS: Systematic review of laboratory-confirmed
      admissions to the Children's Hospital, Soochow University (Suzhou, China).
      RESULTS: Seventy-five children younger than 14 years of age were admitted with
      pH1N1, 70 with H3N2 and three with seasonal H1N1. With pH1N1, the mean age was
      older (36 months versus seven months), the length of stay was longer (nine days
      versus seven days), underlying conditions were more common (29% versus 15%),
      anemia was more common (11% versus 0%) (P<0.05), with trends toward more
      secondary bacterial pneumonia and intensive care unit care, compared with
      seasonal influenza. Two of the 75 children with pH1N1 died versus no deaths in
      children with seasonal influenza. None of the children had received pH1N1,
      seasonal influenza, conjugated pneumococal or Haemophilus influenzae b vaccines.
      CONCLUSION: In China, children hospitalized with pH1N1 influenza differed from
      case series in Canada, Argentina and the United States, suggesting that locale,
      background and health care system influenced the presentation and outcomes of
      pandemic and seasonal influenza.

PMID- 24294276
TI  - Coagulase-negative Staphylococcus, catheter-related, bloodstream infections and
      their association with acute phase markers of inflammation in the intensive care
      unit: An observational study.
AB  - OBJECTIVE: To examine the relationship between the isolation of coagulase
      negative Staphylococcus in blood cultures and acute phase markers of
      inflammation. METHODS: The present study was a prospective observational analysis
      conducted at three medical/surgical intensive care units (ICUs) involving adult
      patients with an expected ICU stay of more than 24 h duration. RESULTS: Of the
      598 patients enrolled, 573 developed suspected bloodstream infection and 434
      (72.6%) had blood cultures sent 24 h after ICU admission; 142 were excluded due
      to positive cultures from other sites. Of the remaining 292 patients, 31 (10.7%)
      grew coagulase-negative Staphylococcus, 59 (20.2%) grew known pathogenic
      organisms and 202 (69.2%) did not grow any organisms in their blood cultures.
      Twenty-five patients without suspicion of infection served as the control group.
      Interleukin (IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) levels were
      highest among the known pathogen group (IL-6 271.8 U/L, PCT 4.6 U/L and CRP 164
      mg/L), were similar between the coagulase-negative Staphylococcus and negative
      culture groups (IL-6 67.0 U/L versus 61.4 U/L [P=1.00]; PCT 1.0 U/L versus 0.9
      U/L [P=0.80]; and CRP 110 mg/L versus 103 mg/L [P=0.75]), and were lowest in the
      control group (IL-6 31.0 U/L, PCT 0.2 U/L and CRP 41.0 mg/L). In the coagulase
      negative Staphylococcus group, patients who died by day 28 had increased
      inflammatory bio-marker levels compared with survivors, although the differences
      were not statistically significant. CONCLUSIONS: Coagulase-negative
      Staphylococcus isolated from blood cultures were associated with lower levels of
      inflammation compared with bloodstream infections due to known pathogens and were
      comparable with levels in patients with negative cultures.

PMID- 24294277
TI  - Recognizing cognitive and psychiatric changes in the post-highly active
      antiretroviral therapy era.
AB  - Amid numerous complications that plague the health and quality of life of people
      living with HIV, neurocognitive and psychiatric illnesses pose unique challenges.
      While there remains uncertainty with respect to the pathophysiology surrounding
      these disorders, their adverse implications are increasingly recognized. Left
      undetected, they have the potential to significantly impact patient well being,
      adherence to antiretroviral treatment and overall health outcomes. As such, early
      identification of HIV-associated neurocognitive disorders (HAND) and psychiatric
      illnesses will be paramount in the proactive management of affected patients. The
      present review focuses on strategies to ensure optimal screening and detection of
      HAND, depression and substance abuse in routine practice. For each topic,
      currently available screening methods are discussed. These include identification
      of risk factors, recognition of relevant symptomatology and an update on
      validated screening tools that can be efficiently implemented in the clinical
      setting. Specifically addressed in the present review are the International HIV
      Dementia Scale, a novel screening equation and algorithm for HAND, as well as
      brief, validated, verbal questionnaires for detection of depression and substance
      abuse. Adequate understanding and usage of these screening mechanisms can ensure
      effective use of resources by distinguishing patients who require referral for
      more extensive diagnostic procedures from those who likely do not. 

PMID- 24294278
TI  - Culture-negative endocarditis diagnosed using 16S DNA polymerase chain reaction.
AB  - 16S DNA polymerase chain reaction (PCR) is a molecular amplification technique
      that can be used to identify bacterial pathogens in culture-negative
      endocarditis. Bacterial DNA can be isolated from surgically excised valve tissue
      or from blood collected in EDTA vials. Use of this technique is particularly
      helpful in identifying the bacterial pathogen in cases of culture-negative
      endocarditis. A case involving a 48-year-old man who presented with severe aortic
      regurgitation and a four-month prodrome of low-grade fever is reported. Blood and
      valve tissue cultures following valve replacement were negative. A valve tissue
      sample was sent for investigation with 16S DNA PCR, which successfully identified
      Streptococcus salivarius and was interpreted as the true diagnosis. A review of
      the literature suggests that 16S DNA PCR from valve tissue is a more sensitive
      diagnostic test than culture. It is also extremely specific, based on a sequence
      match of at least 500 base pairs. 

PMID- 24294279
TI  - The coincidence of necrotizing enterocolitis and rotavirus infections and
      potential associations with cytokines.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal
      disease in neonatal intensive care units. Although the pathogenesis of NEC
      remains unclear, evidence suggests that infections, especially bacterial
      infections, may play an important role. Viral infections may also result in NEC.
      Several outbreaks of NEC associated with rotaviruses have been described
      previously. OBJECTIVE: To investigate the association between rotavirus (RV) and
      serum interleukin (IL)-6 and IL-8 levels in infants with NEC. METHODS: RV
      infections were prospectively studied using antigen detection in the stools of 31
      infants with NEC. Additionally, serum levels of IL-6, IL-8 and tumour necrosis
      factor-alpha were tested using micro-ELISA at 0 h and 48 h after diagnosis of
      NEC. RESULTS: Fecal specimens from 13 infants were positive, while fecal
      specimens from 18 infants were negative for RV according to antigen detection
      (RV+ and RV- groups, respectively). The mortality rate and the severity of NEC
      were not significantly different between the RV+ and RV- groups. IL-6 levels at 0
      h and 48 h after diagnosis of NEC in RV+ infants were lower compared with RV-
      infants, while IL-8 levels were greater at 0 h and 48 h after diagnosis of NEC in
      RV+ infants compared with RV- infants. CONCLUSION: A high prevalence of RV
      infection in neonates with NEC was found. Decreased IL-6 levels and increased IL
      8 and tumour necrosis factor-alpha levels in RV+ neonates with NEC suggests a
      role for RV in NEC.

PMID- 24294280
TI  - Mycobacterium marinum infection from sea monkeys.
AB  - A case of cutaneous Mycobacterium marinum infection acquired from Artemia nyos
      (sea monkeys) is presented. The infection was unresponsive to initial
      antimicrobial therapies. A biopsy of a lesion revealed granulomatous inflammation
      with cultures that subsequently grew M marinum. A three-month course of
      clarithromycin provided complete resolution. 

PMID- 24294281
TI  - Invasive Bacillus cereus infection in a renal transplant patient: A case report
      and review.
AB  - Bacillus cereus is a common cause of gastrointestinal diseases. The majority of
      individuals with B cereus-related food poisoning recover without any specific
      treatment. It can, however, rarely cause invasive disease in immunocompromised
      patients. 

PMID- 24294282
TI  - A 45-year-old man with cough and a cavitary lung lesion.

PMID- 24294283
TI  - The use of antiviral drugs for influenza: Guidance for practitioners 2012/2013.
AB  - The present article addresses the use of antiviral drugs in the management of
      seasonal influenza illness for the 2012/2013 season. It updates the previous
      document published in 2011 (1). Noteworthy guidance updates since 2011 include
      the following: Seasonal influenza in 2012/2013 is predicted to be caused by two
      human influenza A and one influenza B strain, all of which are anticipated to
      remain generally susceptible to oseltamivir.The predicted strains are
      A/California/7/2009 (H1N1) pdm09-like, A/Victoria/361/2011 (H3N2)-like and
      B/Wisconsin/1/2010-like (Yamagata lineage). All are included in the seasonal
      influenza vaccine and are susceptible to oseltamivir.Swine-variant H3N2v, which
      has rarely caused infection in humans exposed to infected swine within the past
      year in the United States, is susceptible to oseltamivir. It is not included in
      the current seasonal influenza vaccine.It is still considered that initiation of
      antiviral therapy more than 36 h to 48 h after onset of symptoms is beneficial in
      patients hospitalized with complicated influenza and severe illness.Oseltamivir
      continues to be recommended for the treatment of influenza in pregnant women.The
      use of antiviral drugs among measures to control outbreaks of influenza in closed
      facilities such as correctional institutions is now included in the present
      document. 

PMID- 24294284
TI  - AMMI Canada position paper: 2012 Mandatory influenza immunization of health care
      workers.

PMID- 24294285
TI  - Comparison of late HIV diagnosis as a marker of care for Aboriginal versus non
      Aboriginal people living with HIV in Ontario.
AB  - BACKGROUND: Studies have found that Aboriginal people living with HIV/AIDS
      (APHAs) are more likely than non-APHAs to receive suboptimal HIV care, yet
      achieve similar clinical outcomes with proper care. OBJECTIVE: To compare the
      proportions of individuals diagnosed late with HIV between APHAs and non-APHAs
      within the Ontario HIV Treatment Network Cohort Study (OCS). METHODS: The
      analysis included OCS participants who completed the baseline visit by November
      2009. Two definitions of the outcome of late HIV diagnosis were used: the
      proportion of participants with an AIDS-defining illness (ADI) before or within
      three months of HIV diagnosis; and the proportion of participants with a CD4(+)
      count <200 cells/mL at diagnosis. Logistic regression analysis was used to assess
      the association between Aboriginal ethnicity and late HIV diagnosis. RESULTS:
      APHAs were more likely to be female and have lower income, education and
      employment. No statistically significant differences were noted in the
      proportions receiving a late HIV diagnosis defined by ADI (Aboriginal 5.2% versus
      non-Aboriginal 6.3%; P=0.40). Multivariate logistic regression analysis revealed
      a significant association between Aboriginal ethnicity and late HIV diagnosis
      defined by CD4(+) count after adjusting for age and HIV risk factor (OR 1.55;
      P=0.04). DISCUSSION: APHAs were more likely to have a CD4(+) count <200 cells/mL
      at diagnosis but had similar clinical outcomes from late diagnosis when defined
      by ADI. However, differences may be underestimated due to recruitment limitations
      and selection bias. CONCLUSION: Additional work is needed to address the
      socioeconomic and health care needs of APHAs.

PMID- 24294286
TI  - Children's Provision of Family Caregiving: Benefit or Burden?
AB  - Despite the high numbers of children who provide care to family members in
      industrialized countries, relatively little is known about the impact of
      caregiving on children's development. In this article, issues related to
      children's caregiving, including a discussion of who provides care, the costs and
      benefits of caring, and directions for future research are reviewed. This review
      is intended to stimulate further study of this issue, particularly in clarifying
      who is most vulnerable to caregiving burden and understanding how caregiving
      affects children's lives and development.

PMID- 24294287
TI  - Actinic keratosis underlying cutaneous horn at an unusual site-a case report.
AB  - Cutaneous horns are usually found on chronic sun-damaged skin. A cutaneous horn
      is a rare tumour, often conical, circumscribed, and composed of dead keratin
      usually derived from base keratinocytes. It occurs mainly in association with
      underlying benign, premalignant, and malignant cutaneous diseases. The commonest
      malignancy is squamous cell carcinoma. Thus, to accurately ascertain the nature
      of the condition at the base of the lesion and to rule out malignancy, an
      excision biopsy is indicated. Here, we report a case of cutaneous horn over the
      palmar aspect of the left middle finger in a 45-year-old man whose histopathology
      showed actinic keratosis. 

PMID- 24294288
TI  - Prevention of recurrent urinary tract infections by intravesical administration
      of heparin: a pilot study.
AB  - OBJECTIVE: To assess the effect of bladder instillations using heparin on the
      rate of urinary tract infections in women resistant to standard therapy. PATIENTS
      AND METHODS: The medical records of all women who received bladder instillations
      between May 2009 and January of 2010 at the University of Wisconsin urogynecology
      clinic were reviewed. Eighteen women (mean age 67 years) with a history of
      recurrent urinary tract infections received intravesical instillations (heparin
      40,000 U, 2% lidocaine 8 ml, sodium bicarbonate 4 ml) once weekly for 6 weeks.
      Patients were considered resistant to standard therapy if their condition failed
      to respond to chronic suppression antibiotic therapy; they had chronic infections
      and for this reason could not be placed on chronic suppression; or they were not
      candidates for chronic suppression due to drug allergies. The number of urinary
      tract infections was monitored during treatment and for 6 months after therapy.
      The urinary tract infection rates were compared with the rates of urinary tract
      infection in the 6 months before treatment. RESULTS: Seventy-eight percent of
      patients responded to therapy. Subjects were thought to have responded to therapy
      if there was a greater than 50% reduction in the rate of urinary tract infection.
      Other variables reviewed included evidence of chronic infection, hormonal status,
      glomerular filtration rate, age, body mass index, antibiotic allergies, diabetes,
      hypertension, and chronic antibiotic therapy during bladder instillations. None
      of these variables were found to be statistically significant. CONCLUSION:
      Bladder instillations decreased the rate of urinary tract infection in this pilot
      study; this effect persisted into the post-treatment period. More research is
      needed to confirm these preliminary findings.

PMID- 24294289
TI  - Desmopressin in the treatment of nocturia: clinical evidence and experience.
AB  - Nocturia is a common and bothersome condition experienced by both men and women.
      Studies have suggested that nocturia contributes a level of morbidity to those
      who suffer from the condition, both young and old. Desmopressin has historically
      been utilized to treat conditions such as central diabetes insipidus, certain
      bleeding disorders and primary nocturnal enuresis. Recently, interest has
      increased as to the use of desmopressin (a vasopressin analog) in the treatment
      of adult nocturia, for whom nocturnal polyuria is prevalent. While desmopressin
      has been traditionally administered in tablet and bioequivalent high dose melt
      formulations, newer low-dose orally disintegrating sublingual desmopressin has
      been recently studied to determine safe and efficacious dosing strategies. In
      this review, nocturia and its associated morbidities are discussed, followed by a
      contemporary literature review regarding the safety and efficacy of desmopressin
      for its treatment. 

PMID- 24294290
TI  - Biomarkers in prostate cancer surveillance and screening: past, present, and
      future.
AB  - The use of biomarkers for prostate cancer (PCa) screening, detection, and
      prognostication have revolutionized the diagnosis and management of the disease.
      Current clinical practice has been driven largely by the utilization of prostate
      specific antigen (PSA). The lack of specificity of PSA for PCa has led to both
      unnecessary biopsies and overdiagnosis of indolent cancers. The recent
      controversial recommendation by the United States Preventive Services Task Force
      against PCa screening has highlighted the need for novel clinically useful
      biomarkers. We review the literature on PCa biomarkers in serum, urine, and
      tissue. While these markers show promise, none seems poised to replace PSA, but
      rather may augment it. Further validation and consideration of how these novel
      markers improve clinical outcome is necessary. The discovery of new genetic
      markers shows promise in stratifying men with aggressive PCa. 

PMID- 24294291
TI  - Considerations for patient selection for focal therapy.
AB  - Focal therapy for prostate cancer is a nascent and emerging field. As such, the
      patient selection criteria for this new treatment paradigm are evolving in
      parallel to both the technology on which this approach depends and to our
      unfolding understanding of the natural history of prostate cancer. Until, and
      while, prospective trials of focal therapy are being reported, patient selection
      criteria will be flexible and very dependent on the therapeutic goals. We must
      carefully define the therapeutic intentions of focal therapy before engaging in
      the actual process of determining optimal patient selection. The therapeutic
      intent will define the most appropriate candidate for such therapy. Patient
      selection encompasses multiple complex issues including the type of prostate
      biopsy (12 core transrectal versus mapping transperineal) to the type of imaging
      (multiparametric magnetic resonance imaging or enhanced ultrasound) to the
      specific anatomical location of the disease within the prostate (apex, mid
      prostate, base) and a comprehensive assessment of the patient's overall health
      and life expectancy. It is not as simple as saying a patient with a certain grade
      or a certain number of cores is or is not appropriate for focal therapy. There
      are many more considerations for a reasonable and thoughtful approach to this new
      treatment. 

PMID- 24294294
TI  - Mental and physical health parity: not a luxury but a necessity.

PMID- 24294292
TI  - Recent developments in the treatment of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) management has been imbued with new interest, in large
      part due to the recent success of new treatment options for advanced and
      metastatic disease. This has also been accompanied by less generally well known
      advances in the understanding of the molecular characterizations of subtypes of
      RCC with potential to lead to new therapeutic options. Additionally, the urologic
      oncology community is focusing on nephron-sparing surgical approaches with
      limited surgery if possible, and in conjunction with interventional radiologists,
      on ablative procedures for incidentally determined small renal masses. This
      report reviews some of the new biologic findings of adenocarcinoma of the kidney,
      and reviews the new therapeutics which continue to change the landscape for
      treatment of RCC. 

PMID- 24294295
TI  - Vitamin D and the perinatal period in women suffering from schizophrenia.

PMID- 24294293
TI  - Current status of minimally invasive endoscopic management of ureteric
      strictures.
AB  - Endourological techniques are used more often nowadays in the treatment of
      ureteric strictures of various etiologies. Advances in technology have provided
      new tools to the armamentarium of the endoscopic urological surgeon. Numerous
      studies exist that investigate the efficiency and safety of each of the
      therapeutic modalities available. In this review, we attempt to demonstrate the
      available and contemporary evidence supporting each minimally invasive modality
      in the management of ureteric strictures. 

PMID- 24294296
TI  - Training teachers to teach mental health skills to staff in primary care settings
      in a vast, under-populated area.
AB  - Background The Arkhangelsk Oblast is an area the size of France with a sparsely
      distributed population. The existing primary care staff have had very little
      training in the management of mental health disorders, despite the frequency of
      these disorders in the population. They requested special teaching on depression,
      suicide, somatisation and alcohol problems. Methods An educational intervention
      was developed in partnership with mental health and primary care staff in Russia,
      to develop mental health skills using established, evidence-based methods. After
      a preliminary demonstration of teaching methods to be employed, a 5-day full-time
      teaching course was offered to trainers of general practitioners and feldshers.
      Results The findings are presented by providing details of improvements that
      occurred over a 3-month period in four areas, namely depression in primary care,
      somatic presentations of distress, dealing with suicidal patients, and alcohol
      problems. We present preliminary data on how the training has generalised since
      our visits to Archangelsk. Conclusions Teachers who are used to teaching by
      didactic lectures can be taught the value of short introductory talks that invite
      discussion, and mental health skills can be taught using role play. The content
      of such training should be driven by perceived local needs, and developed in
      conjunction with local leaders and teachers within primary care services. Further
      research will be needed to establish the impact on clinical outcomes. 

PMID- 24294297
TI  - Attitudes and sexual behaviours of unmarried people with HIV/AIDS living in the
      Niger Delta region of Nigeria.
AB  - Background Increasing morbidity and mortality associated with HIV/AIDS may be
      attributable to the lifestyle of individuals. Appropriate sexual behaviour and
      lifestyle modification may be helpful strategies for prevention and control of
      HIV/AIDS in many countries. Aim The study was designed to assess the impact of
      attitudes and sexual behaviour on control of HIV/AIDS among unmarried people
      living with HIV/AIDS in Uyo, a community in the Niger Delta region of Nigeria.
      Method A total of 365 unmarried individuals living with HIV/AIDS were assessed at
      the HIV clinic of the University of Uyo Teaching Hospital. Attitudes and sexual
      behaviour were evaluated using the Attitude and Sexual Behaviour Questionnaire
      adapted from previous studies. Results Of the 365 individuals living with
      HIV/AIDS, 142 (38.9%) were male and 223 (61.1%) were female. The majority of the
      subjects were below 50 years of age. The mean ages (+/- SD) of men and women were
      36.8 +/- 3.9 and 29.2 +/- 1.7 years, respectively. Sexual attitudes and
      behaviours were variable. There was no change in the partner's reaction to sex
      for 28.9% of men and 27.8% of women, abstinence in 7.7% of men and 8.1% of women,
      and breakdown of the relationship with the partner for 4.9% of men and 7.2% of
      women. More women than men agreed to undergo testing after their partners had
      tested positive for HIV. Sexual activity was higher in women than men, with 4.9%
      of men and 10.3% of women reporting daily sexual intercourse, 16.2% of men and
      15.7% of women reporting weekly intercourse, and occasional sexual intercourse
      being reported by 44.4% of both men and women. After testing positive, 58.4% of
      male partners and 56.9% of female partners were persuaded to use condoms during
      sexual intercourse. Conclusion This study has demonstrated unhealthy attitudes
      and sexual behaviour among individuals living with HIV/AIDS in the Niger Delta
      region of Nigeria. This can potentially limit efforts and investment in
      controlling HIV/AIDS in this region. Therefore there is a need to initiate
      concrete policies and programmes that would encourage people living with HIV/AIDS
      in the Niger Delta region to adopt a healthy lifestyle. 

PMID- 24294298
TI  - The Northampton Physical Health and Wellbeing Project: the views of patients with
      severe mental illness about their physical health check.
AB  - Background Annual health checks are recommended for people with severe mental
      illness, as they are at high risk of cardiovascular disease. We trained practice
      nurses from six primary care centres in Northampton, in the UK, how to deliver
      health checks for this population. Aims The purpose of this study was to examine
      patients' views about the physical health check delivered by a nurse trained in
      the Northampton Physical Health and Wellbeing (PhyHWell) project. Method We
      interviewed five patients from three primary care centres using a topic guide.
      Results From a total of 29 patients who were invited, five attended. They had a
      good understanding of the importance of a healthy diet and taking regular
      exercise, but did not appear to be aware of the risk of cardiovascular disease.
      Being treated consistently by the same healthcare professional and/or by a nurse
      was cited as a helpful factor in managing their physical health. Most of the
      patients were glad to be invited for a health check and thought that it was
      worthwhile. They would have liked more information about blood tests and
      medication. All of the patients reported that they had started to make changes to
      their lifestyle since the health check. Recommendations Training for practice
      nurses to provide physical health checks for people with severe mental illness
      should emphasise the patients' views of what will make them effective. 

PMID- 24294299
TI  - Does consanguinity increase the risk of schizophrenia? Study based on primary
      health care centre visits.
AB  - Background Consanguinity has been suggested as a risk factor for the development
      of schizophrenia in offspring in some Middle Eastern countries. Aim The purpose
      of this study was to review the frequency, pattern of parental consanguinity, and
      family history of schizophrenia among schizophrenia patients in Qatar, and to
      determine their impact on the associated risk factors. Design This is a cross
      sectional study which was conducted between January 2009 and December 2010, in
      the setting of primary health care (PHC) centres of the Supreme Council of
      Health, State of Qatar. Subjects A total of 1491 patients aged 18-55 years were
      approached, of whom 1184 individuals agreed to participate in the study, giving a
      response rate of 79.4%. Methods The study was based on face-to-face interviews
      using a specially designed questionnaire that covered sociodemographic
      characteristics and genetic and other biological factors (e.g. obstetric
      complications), and a diagnostic screening questionnaire which consisted of six
      questions about the symptoms of schizophrenia. The diagnostic screening
      questionnaire was reviewed and used to calculate the final score, which
      determined a provisional diagnosis. The psychiatrists discussed the psychiatric
      diagnosis and confirmed it using DSM-IV criteria. The degree of consanguinity
      between the patient's parents was recorded. Consanguinity was evaluated based on
      the coefficient of inbreeding (F), which is the probability of homozygosity.
      Results More than half of the schizophrenia patients were female (57.1%) and over
      45 years of age (62.5%). A family history of schizophrenia was significantly more
      common in parents of schizophrenia patients than in the Arab population without
      schizophrenia (24.6% vs. 17.1%; P = 0.038). Parental consanguinity was elevated
      among the patients with schizophrenia (41.3%) with a higher mean coefficient of
      inbreeding (0.04356 +/- 0.028) than in non-schizophrenic subjects (28.7%) with a
      lower mean coefficient of inbreeding (0.0298 +/- 0.035). Schizophrenia diagnoses
      were more frequent among the offspring of consanguineous parents than among the
      offspring of non-consanguineous parents. Conclusion The substantial risk observed
      in the present study reveals that consanguinity is an important risk factor for
      schizophrenia in Qatar. In addition, the study confirms that the higher familial
      risks provide strong genetic epidemiological evidence for the overall heritable
      effects in the aetiology of schizophrenia. 

PMID- 24294300
TI  - Supportive family relationships and adolescent health in the socio-cultural
      context of Iran: a qualitative study.
AB  - Parents have a critical role in adolescent health. The association of
      adolescents' perceptions of family relationships with adolescent health was
      investigated using a sample of 67 female adolescents who participated in eight
      focus group discussions, utilising a purposeful sampling method. All tape
      recorded data were fully transcribed and content analysis was performed. Three
      themes were identified, namely emotional support, responsible parents and well
      informed parents. With regard to some of the challenges in Iranian adolescents'
      relationships with their parents, it is necessary to educate parents to be alert
      to their role in adolescent health. 

PMID- 24294301
TI  - A feasibility study of a telephone-supported self-care intervention for
      depression among adults with a comorbid chronic physical illness in primary care.
AB  - Objective We assessed the feasibility and acceptability to patients of a
      telephone-supported self-care intervention for depression among adults aged 40
      years or over with one of six targeted chronic physical illnesses and comorbid
      depressive symptoms in family practice settings. Methods An open, uncontrolled
      trial (feasibility study) was conducted among patients treated in Montreal family
      practices. Eligible patients were aged 40 years or over, had one or more of the
      targeted chronic physical illnesses for at least 6 months (arthritis,
      hypertension, diabetes, heart disease, asthma and chronic obstructive pulmonary
      disease) and were evaluated as having at least mild depressive symptoms (a score
      of >= 5 on the 9-item Patient Health Questionnaire, PHQ-9). Participants received
      a package of six self-care tools (information booklet, video, Internet programme,
      action plan, workbook and mood-monitoring tool) with telephone support by a lay
      coach for up to 6 months. Results In total, 63 eligible patients provided written
      consent and completed the baseline interview; 57 (90%) and 55 (87%) patients
      completed 2-month and 6-month follow-up interviews, respectively. The mean number
      of telephone calls made by coaches to participants was 10.5 (SD 4.0), and the
      average length of these calls was 10.6 minutes. At the 6-month follow-up, 83.6%
      of the participants reported that one or more of the tools were helpful.
      Clinically significant improvements were seen in depressive symptoms (as assessed
      by the PHQ-9) at 6 months, with an effect size of 0.88 (95% CI, 0.55, 1.14).
      Conclusion A telephone-supported self-care intervention for depression was
      feasible, was acceptable to patients, and was associated with a significant 6
      month improvement in depressive symptoms. A randomised trial of this intervention
      is justified. 

PMID- 24294302
TI  - Factors associated with maternal depressive symptoms among low-income, African
      American smokers enrolled in a secondhand smoke reduction programme.
AB  - Introduction Maternal depressive symptoms increase the risk of poor maternal and
      child health outcomes, and are a primary barrier to health behaviour change.
      Social cognitive theory can guide our understanding of risk factors that may have
      an impact on maternal depressive symptoms. The aim of this paper was to
      understand the correlates of maternal depressive symptoms among low-income
      African American smokers completing a 16-week intervention trial to reduce young
      children's second-hand smoke exposure (SHSe). Methods This study presents a
      secondary analysis of depression symptoms among 227 maternal smokers completing
      the SHSe-reduction trial. The end-of-treatment Center of Epidemiologic Studies
      Depression Scale (CES-D) score was used to assess depressive symptoms
      (dichotomised as 0 = score of < 16 and 1 = score of >= 16). Multivariate logistic
      regression analysis was used to test the one-way hypothesis that odds of
      significant depressive symptoms would be associated with greater total number of
      household smokers, greater number of paediatric sick visits, greater daily
      exposure of child to cigarette smoke by their mother, greater life-event stress,
      and lower social support, marital status, employment status and level of
      educational attainment. Results Number of household smokers (OR = 1.57, P =
      0.049), social support (OR = 0.88, P < 0.001) and life-event stress (OR = 1.04, P
      = 0.001) predicted significant maternal depressive symptoms; all other variables
      were not significant predictors in the model. Conclusion Number of household
      smokers is a novel risk factor for understanding significant maternal depressive
      symptoms in the context of a childhood SHSe-reduction trial. Improving our
      understanding of the household-level social milieu in the context of SHSe
      reduction interventions will assist in reducing the risk of maternal depressive
      symptoms. 

PMID- 24294303
TI  - Clinical experience with duloxetine in the management of chronic musculoskeletal
      pain. A focus on osteoarthritis of the knee.
AB  - Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with
      central nervous system activity. Its analgesic efficacy in central pain is
      putatively related to its influence on descending inhibitory pain pathways. The
      analgesic efficacy of duloxetine has been demonstrated in four distinct chronic
      pain conditions. These include neuropathic pain associated with diabetic
      peripheral neuropathy, fibromyalgia, chronic low back pain, and osteoarthritis
      knee pain (OAKP). The purpose of this review is to examine the clinical efficacy
      and safety of duloxetine in the management of chronic OAKP. Three separate
      randomized, double-blind placebo-controlled trials have demonstrated that (1) a
      clinically meaningful decrease in pain severity occurs at about 4 weeks relative
      to placebo, (2) patients receiving duloxetine report better improvements in
      physical functioning relative to placebo, (3) duloxetine is safe and effective
      when used adjunctively with nonsteroidal anti-inflammatory drugs, and (4) that
      there are no new safety signals beyond what has been observed in other
      indications. 

PMID- 24294304
TI  - Catastrophic antiphospholipid syndrome: how to diagnose a rare but highly fatal
      disease.
AB  - Antiphospholipid syndrome (APS) is a multisystem autoimmune condition
      characterized by vascular thromboses and/or pregnancy loss associated with
      persistently positive antiphospholipid antibodies (aPL). Catastrophic APS (CAPS)
      is the most severe form of APS with multiple organ involvement developing over a
      short period of time, usually associated with microthrombosis. 'Definite' and
      'probable' CAPS have been defined based on the preliminary classification
      criteria; however, in a real-world setting, aPL-positive patients with multiple
      organ thromboses and/or thrombotic microangiopathies exist who do not fulfill
      these criteria. Previous APS diagnosis and/or persistent clinically significant
      aPL positivity is of great importance for the CAPS diagnosis; however, almost
      half of the patients who develop CAPS do not have a history of aPL positivity.
      The purpose of this paper is to summarize the diagnostic challenges and the
      recently updated diagnostic algorithms for CAPS providing a 'step-by-step'
      approach for clinicians (and researchers) in the assessment of patients with
      multiple organ thromboses. 

PMID- 24294305
TI  - Canakinumab in patients with cryopyrin-associated periodic syndrome: an update
      for clinicians.
AB  - The cryopyrin-associated periodic syndrome (CAPS) is a very rare disease. It is
      estimated that there are 1-2 cases for every 1 million people in the US and 1 in
      every 360,000 in France. However, many patients are diagnosed very late or not at
      all, meaning the real prevalence is likely to be higher. CAPS encompasses the
      three entities of familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells
      syndrome (MWS), and neonatal-onset multisystem inflammatory disease
      (NOMID)/chronic infantile neurologic, cutaneous and articular (CINCA) syndrome.
      They have in common a causative mutation in the NLRP3 gene. The altered gene
      product cryopyrin leads to activation of the inflammasome which in turn is
      responsible for excessive production of interleukin (IL)-1beta. IL-1beta causes
      the inflammatory manifestations in CAPS. These appear as systemic inflammation
      including fever, headache or fatigue, rash, eye disease, progressive
      sensorineural hearing loss, musculoskeletal manifestations and central nervous
      system (CNS) symptoms (NOMID/CINCA only). With the advent of IL-1 Inhibitors,
      safe and effective therapeutic options became available for this devastating
      disease. To prevent severe and possible life-threatening disease sequelae, early
      and correct diagnosis and immediate initiation of therapy are mandatory in most
      patients. Canakinumab is a fully human monoclonal IgG1 anti-IL-1beta antibody. It
      provides selective and prolonged IL-1beta blockade and has demonstrated a rapid
      (within hours), complete and sustained response in most CAPS patients without any
      consistent pattern of side effects. Long-term follow-up trials have demonstrated
      sustained efficacy, safety and tolerability. Canakinumab is approved by the US
      Food and Drug Administration for FCAS and MWS and by European Medicines Agency
      for treatment of all three phenotypes of CAPS. 

PMID- 24294307
TI  - SENSING DNA WITH ALTERNATING CURRENTS USING A NANOGAP SENSOR EMBEDDED IN A
      NANOCHANNEL DEVICE.
AB  - We report an integrated nanochannel/nanoelectrode sensor for the detection of DNA
      using alternating currents. We find that DNA can be detected using platinum as
      the metal for the detecting electrodes, with a signal to noise ratio exceeding
      10. We argue that the signal is at least in part electrochemical in nature, thus
      holds the promise to yield a sequence-dependent signal. However, we also find
      that for large voltages, DNA attaches irreversibly to the driving electrodes.

PMID- 24294308
TI  - Valgus extension femoral osteotomy to treat "hinge abduction" in Perthes'
      disease.
AB  - PURPOSE: "Hinge abduction" is a complication of Perthes' disease caused by
      impingement of the extruded superolateral portion of the femoral head against the
      lateral lip of the acetabulum. Catterall first described femoral valgus extension
      osteotomy (VGEO) to treat this condition. We report the results of this operation
      in 16 cases of Perthes' disease with "hinge abduction". METHODS: Sixteen hips in
      16 patients affected by Perthes' disease and "hinge abduction" were operated on
      at a mean age of 10.1 years and followed up an average of 6.5 years later. Before
      surgery, the mean Iowa hip score was 44.4 points. Preoperative radiographs were
      taken with the affected hip in maximum adduction in order to calculate the amount
      of valgus correction. The osteotomy was performed between the greater and the
      lesser trochanter, and it was fixed with a hip plate. RESULTS: All the
      osteotomies healed uneventfully. At follow-up, no patient complained of pain and
      hip abduction ranged from 20 degrees  to 45 degrees . Four out of the 16 patients
      had a moderate limp, and 12 had an improvement in gait pattern compared to
      preoperatively. At follow-up, the Iowa hip score totaled a mean of 83.6 points,
      with a statistically significant improvement in comparison to the preoperative
      evaluation. At follow-up, two hips were classified as Stulberg II-III, ten hips
      as Stulberg III, and four as Stulberg IV. CONCLUSIONS: In our hands, VGEO was an
      effective procedure to treat "hinge abduction" in severe Perthes' disease with
      satisfactory results. The main limitation of our study is its short follow-up.

PMID- 24294309
TI  - The effect of Dega acetabuloplasty and Salter innominate osteotomy on acetabular
      remodeling monitored by the acetabular index in walking DDH patients between 2
      and 6 years of age: short- to middle-term follow-up.
AB  - INTRODUCTION: The surgical management of neglected developmental dysplasia of the
      hip (DDH) in walking children has always been a challenge to orthopedic surgeons.
      The aim of this study was to evaluate the short- to middle-term clinical and
      radiographic results of the management of DDH. PATIENTS AND METHODS: Patients
      less than 6 years old using two of the most commonly used osteotomies, namely,
      Salter innominate osteotomy and the Dega acetabuloplasty. Special attention was
      paid to acetabular remodeling after concentric reduction, which was monitored by
      the acetabular index, that, in turn, was measured preoperatively, immediately
      postoperatively, every 6 months, and at the final follow-up examination. RESULTS:
      The final overall clinical end results were favorable (excellent or good) in 93
      hips (85.3 %). There was a marked improvement of the acetabular coverage during
      the follow-up period, which proved the good remodeling potential of the
      acetabulum for this particular age group after concentric reduction was achieved
      and maintained. CONCLUSION: Both osteotomy types were found to be adequate for
      the management of neglected walking DDH patients under the age of 6 years.

PMID- 24294310
TI  - Comparing caudal and intravenous ketamine for supplementation of analgesia after
      Salter innominate osteotomy.
AB  - PURPOSE: Previous studies claim that caudal administration of ketamine causes
      effective analgesia. The aim of this study was to assess the clinical
      effectiveness of ketamine after caudal or intravascular administration in
      pediatric patients that underwent orthopedic surgery to distinguish between local
      and systemic analgesia. METHODS: After the induction of general anesthesia, 36
      patients, aged 18 months to 10 years, assigned to undergo orthopedic surgery,
      received a caudal injection of bupivacaine and were randomly blinded into two
      groups: one group received 1 mg/kg S(+)-ketamine as the caudal group and the
      other group received 1 mg/kg S(+)-ketamine as the intravascular group.
      Postsurgical measurements included the effectiveness of postsurgical analgesia,
      which was assessed by using the observational pain scale (OPS), duration of
      analgesia, sedation score, and hemodynamic and respiratory monitoring. RESULTS:
      The mean time to first analgesia was clearly longer in the caudal ketamine group
      (13.35 h) than in the intravenous ketamine (9.93 h) group (P < 0.01). During the
      24-h observation time, fewer children asked for additional analgesic drugs in the
      caudal group (8 of 18, 44.4 %) than in the intravenous group (12 of 18, 66.6 %; P
      = 0.01). The times to first micturation and spontaneous leg movements and the
      incidence of nausea and vomiting were similar in the two groups. The OPS and
      sedation scores after operation showed no obvious differences between the groups
      at any time. CONCLUSION: Although caudal ketamine provides good postsurgical
      analgesia due to its potential neurotoxicity and only small clinical differences
      with intravenous ketamine, the administration of intravenous ketamine might be a
      reasonable option to potentially extend the postsurgical analgesic effect of the
      caudal administration of local anesthetics in children undergoing Salter
      osteotomy.

PMID- 24294311
TI  - Orthopedic surgery and mobility goals for children with cerebral palsy GMFCS
      level IV: what are we setting out to achieve?
AB  - BACKGROUND: Multilevel orthopedic surgery is considered to be the gold standard
      treatment for ambulatory children with cerebral palsy (CP), classified at levels
      I, II, or III according to the Gross Motor Function Classification System
      (GMFCS). Hip enlocation and stability are the main goals of orthopedic
      intervention in the GMFCS level IV subgroup and are well researched; however,
      there is no evidence to date to support or challenge the effectiveness of
      orthopedic treatment to preserve functional mobility in this patient group. The
      aim of this study was to evaluate the results of orthopedic surgery to maintain
      or restore standing transfers and supported walking in children with CP at GMFCS
      level IV. METHODS: Twenty-two children with CP GMFCS level IV who underwent
      orthopedic surgery to improve mobility between the years 2004 and 2008 were
      included in this study. A retrospective chart review was performed and a
      satisfaction questionnaire sent to all patients. The primary outcome measure was
      the attainment and maintenance of mobility goals 2 years post-surgery. The
      secondary outcome measures were family/patient satisfaction, Functional Mobility
      Scale (FMS), and complications. RESULTS: The two goals identified by the patients
      and carers were standing transfers and supported walking. At the 2-year post
      surgery assessment, 14 children (63.6 %) did not reach their pre-determined
      goals. In the questionnaire, 21.4 % of the families reported that surgery was not
      beneficial. The FMS score remained unchanged in 95.4 % of the patients. Fourteen
      patients (63.6 %) had at least one complication that prolonged their post
      operative rehabilitation (e.g., neuropraxia). CONCLUSION: This study suggests
      that orthopedic surgery in children with CP at GMFCS level IV is unlikely to
      maintain or restore mobility. Furthermore, it carries a significant risk of
      complications. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 24294312
TI  - The talar axis-first metatarsal base angle in CVT treatment: a comparison of
      idiopathic and non-idiopathic cases treated with the Dobbs method.
AB  - PURPOSE: Congenital vertical talus (CVT) appears as an idiopathic or non
      idiopathic deformity. In this study, we analysed the talar axis-first metatarsal
      base angle (TAMBA) values of idiopathic and non-idiopathic CVT cases treated with
      the Dobbs method. MATERIALS AND METHODS: Between January 2007 and July 2012, 20
      cases of CVT were treated, starting with a manipulation, casting and a minimally
      invasive surgical approach. We analysed retrospectively the TAMBA values in
      idiopathic and non-idiopathic CVT. As a new indicator for the mobility in the
      talonavicular complex, we used the difference of the TAMBA in neutral position
      and the TAMBA in plantarflexion. TAMBA measurements of CVT successfully treated
      with the Dobbs method were compared to TAMBA values of CVT unsuccessfully treated
      using a minimally invasive approach. RESULTS: Out of 20 CVT, 14 were successfully
      treated with the Dobbs method. Of these 14, five feet were non-idiopathic and
      nine feet were idiopathic. Six feet did not have complete correction following
      the Dobbs protocol, and were associated with arthrogryposis or caudal regression
      syndrome. The initial TAMBA in idiopathic feet ranged from 70 to 110 degrees 
      (mean 88 degrees ). The TAMBA in non-idiopathic feet ranged from 75 to 128
      degrees  (mean 105). Feet successfully treated with the Dobbs method had an
      initial TAMBA between 74 and 110 degrees  (mean 87 degrees ). Feet unsuccessfully
      treated with the Dobbs method had an initial TAMBA between 95 and 128 degrees 
      (mean 118 degrees ).The measurement difference between the TAMBA in neutral and
      plantarflexion positions in cases unsuccessfully treated with the Dobbs method
      were smaller compared to values of feet successfully treated with the Dobbs
      method. These differences were statistically significant (p < 0.0001).
      CONCLUSION: In our series, the success of the Dobbs method in CVT treatment
      depended on the flexibility in the talonavicular complex. The TAMBA value and
      TAMBA difference (TAMBA neutral minus TAMBA plantarflexion) express the
      flexibility in the talonavicular joint and could be predictive for the success of
      a minimally invasive treatment. Only in a few cases is the success of the Dobbs
      method limited. These feet are associated with a TAMBA greater than 120 degrees 
      in neutral position and, particularly, a TAMBA difference smaller than 25 degrees
      .

PMID- 24294315
TI  - Re: Feng L, Do P, Aiona M, Feng J, Pierce R, Sussman M (2012) Comparison of
      hamstring lengthening with hamstring lengthening plus transfer for the treatment
      of flexed knee gait in ambulatory patients with cerebral palsy. J Child Orthop
      6:229-235.

PMID- 24294316
TI  - Response to letter re: Comparison of hamstring lengthening with hamstring
      lengthening plus transfer for treatment of flexed knee gait in ambulatory
      patients with cerebral palsy.

PMID- 24294313
TI  - Prevalence of vitamin D insufficiency in Swiss teenagers with appendicular
      fractures: a prospective study of 100 cases.
AB  - BACKGROUND: The significance of subclinical vitamin D deficiency in the
      pathogenesis of fractures in children and adolescents currently remains unclear.
      OBJECTIVE: We aimed to determine the prevalence of vitamin D insufficiency and
      its effect on bone mineral density (BMD) and bone mineral content (BMC) values in
      a collective of Swiss Caucasian children with a first episode of appendicular
      fracture. DESIGN AND METHODS: One hundred teenagers with a first episode of
      appendicular fracture [50 upper limb fractures (group 1) and 50 lower limb
      fractures (group 2)] and 50 healthy controls (group 3) were recruited into a
      cross-sectional study. The BMC and BMD values were measured by dual-energy X-ray
      absorptiometry, and serum 25 hydroxyvitamin D [25(OH)D] was assessed by
      electrochemiluminescence immunoassays. RESULTS: From the 100 injured teenagers in
      the study, 12 % had deficient vitamin D levels (<20 ng/mL; <50 nmol/L) and 36 %
      had insufficient levels (>=20 <30 ng/mL; >=50 <78 nmol/L), whereas 6 and 34 % of
      healthy controls were, respectively, vitamin D deficient and insufficient. There
      were no significant differences for serum 25(OH)D levels, L2-L4 BMD Z-score, and
      L2-L4 BMC Z-score variables (p = 0.216) between the three groups nor for the
      calcaneal BMD Z-score variables (p = 0.278) between healthy controls and lower
      limb fracture victims. Investigations on the influences of serum 25(OH)D on BMD
      and BMC showed no correlation between serum 25(OH)D and L2-L4 BMD Z-scores (r = 
      0.15; p = 0.135), whereas low but significant inverse correlations were,
      surprisingly, detected between serum 25(OH)D and calcaneal BMD Z-scores (r = 
      0.21; p = 0.034) and between serum 25(OH)D and L2-L4 BMC Z-scores (r = -0.22; p =
      0.029). CONCLUSIONS: A significant proportion of Swiss Caucasian teenagers were
      vitamin D insufficient, independent of limb fracture status, in our study.
      However, this study failed to show an influence of low vitamin D status on BMD
      and/or BMC of the lumbar spine and heel.

PMID- 24294314
TI  - Titanium elastic nail in femur fractures as an alternative to spica cast in
      preschoolers.
AB  - PURPOSE: Titanium elastic nail (TEN) as an alternative to traction and spica cast
      in preschool children has not been widely studied for its safety and
      effectiveness. METHODS: A cohort of 59 children with 59 fractures (non
      pathological; not involving condyles or cervicotrochanteric area) were
      retrospectively examined. Their mean age was 4.5 +/- 0.9 years and their mean
      weight was 14.5 +/- 3.7 kg. All but five were closed (21 transverse, 19 oblique
      and 19 spiral). Thirty-five were caused by motor vehicle accidents and 24 by
      falls. There were six upper third, 27 upper-middle junction, 14 middle third,
      seven lower-middle junction, and five lower third fractures. RESULTS: The mean
      follow-up was 41.8 +/- 4.3 months, the mean hospital stay was 1.3 +/- 0.87 days,
      and the mean time to nail removal was 20.3 +/- 10.2 weeks. The mean time to union
      was 7.6 +/- 1.5 weeks. Union was significantly correlated to age (p = 0.000) and
      fracture shape (p = 0.005), but not to the fracture level, nature, or mechanism.
      Shortening of >=1.0 cm occurred in two cases (3.4 %), with an overall mean of
      0.06 +/- 0.21 cm. Shortening was significantly correlated to the fracture shape
      (p = 0.020), but not to the level. Overgrowth of >=1 cm occurred in seven cases
      (11.9 %), with an overall mean of 0.22 +/- 0.41 cm. Overgrowth was
      insignificantly correlated to the fracture level and shape. Frontal angulation of
      5-9o occurred in six cases (10.2 %) and sagittal angulation of 3-7o occurred in
      seven cases (11.9 %). A rotational deformity of 10o occurred in two cases (3.4
      %). Five cases had a painful nail end (8.5 %) and exteriorization with
      superficial infection occurred in two cases (3.4 %). CONCLUSION: TEN is a
      dependable, safe, and cost-effective alternative to traction and cast in
      preschool children.

PMID- 24294317
TI  - Retraction Note: Clinical effectiveness of continuous passive motion (CPM)
      following femoroacetabular impingement surgery in adolescents.

PMID- 24294319
TI  - A chronic flexion-distraction injury with a "fistulous wither" on the split
      spinous process of the L1 vertebra-a case report of a modified transpedicle wedge
      osteotomy.

PMID- 24294320
TI  - News from the NIH: highlights in implementation science from the National Cancer
      Institute and the National Institute of Mental Health.

PMID- 24294318
TI  - Strategies to target tumors using nanodelivery systems based on biodegradable
      polymers, aspects of intellectual property, and market.

PMID- 24294321
TI  - News from the CDC: chronic fatigue syndrome (CFS) and standardized patient videos
      - a novel approach to educating medical students about CFS.

PMID- 24294322
TI  - Results from the dissemination of an evidence-based telephone-delivered
      intervention for healthy lifestyle and weight loss: the Optimal Health Program.
AB  - Despite proven efficacy, there are few published evaluations of telephone
      delivered interventions targeting physical activity, healthy eating, and weight
      loss in community dissemination contexts. This study aims to evaluate participant
      and program outcomes from the Optimal Health Program, a telephone-delivered
      healthy lifestyle and weight loss program provided by a primary health care
      organization. Dissemination study used a single-group, repeated measures design;
      outcomes were assessed at 6-month (mid-program; n = 166) and 12-month (end of
      program; n = 88) using paired analyses. The program reached a representative
      sample of at-risk, primary care patients, with 56 % withdrawing before program
      completion. Among completers, a statistically significant improvement between
      baseline and end of program was observed for weight [mean change (SE) -5.4 (7.0)
      kg] and waist circumference [-4.8 (9.7) cm], underpinned by significant physical
      activity and dietary change. Findings suggest that telephone-delivered weight
      loss and healthy lifestyle programs can provide an effective model for use in
      primary care settings, but participant retention remains a challenge. 

PMID- 24294323
TI  - Dissemination of an evidence-based telephone-delivered lifestyle intervention:
      factors associated with successful implementation and evaluation.
AB  - To inform wider-scale dissemination efforts of health behavior change
      interventions, we need to better understand factors associated with successful
      implementation and evaluation in nonresearch settings. Using the experience of
      the Optimal Health Program dissemination (OHP), a 12-month evidence-based
      telephone-delivered intervention for physical activity, healthy eating, and
      weight loss, we provide a detailed account according to the reach,
      efficacy/effectiveness, adoption, implementation, and maintenance (RE-AIM)
      framework of the supports that were needed to facilitate the delivery and
      evaluation of the program in an applied community-based primary health care
      setting. Substantial initial research support including development of data
      collection procedures, staff training in intervention protocols, and ongoing
      support for fidelity of data collection and intervention delivery, as well as
      evaluation and reporting of outcomes was required. The RE-AIM framework can
      highlight common elements that will require attention from researchers to promote
      success of programs in applied settings. 

PMID- 24294324
TI  - Implementation and evaluation of an incentivized Internet-mediated walking
      program for obese adults.
AB  - In response to rising health care costs associated with obesity rates, some
      health care insurers are adopting incentivized technology-enhanced wellness
      programs. The purpose of this study is to evaluate the large-scale implementation
      of an incentivized Internet-mediated walking program for obese adults and to
      examine program acceptance, adherence, and impact. A mixed-methods evaluation was
      conducted to investigate program implementation, acceptance, and adherence rates,
      and physical activity rates among program participants. Program implementation
      was shaped by national and state policies, data security concerns, and challenges
      related to incentivizing participation. Among 15,397 eligible individuals, 6,548
      (43 %) elected to participate in the walking program, achieving an average of
      6,523 steps/day (SD 2,610 steps). Participants who uploaded step counts for 75 %
      of days for a full year (n = 2,885) achieved an average of 7,500 steps (SD
      3,093). Acceptance and participation rates in this incentivized Internet-mediated
      walking program suggest that such interventions hold promise for engaging obese
      adults in physical activity. 

PMID- 24294325
TI  - Implementing point of care "e-referrals" in 137 clinics to increase access to a
      quit smoking internet system: the Quit-Primo and National Dental PBRN HI-QUIT
      Studies.
AB  - Integrating electronic referral systems into clinical practices may increase use
      of web-accessible tobacco interventions. We report on our feasibility evaluation
      of using theory-driven implementation science techniques to translate an e
      referral system (ReferASmoker.org) into the workflow of 137 community-based
      medical and dental practices, including system use, patient registration,
      implementation costs, and lessons learned. After 6 months, 2,376 smokers were e
      referred (medical, 1,625; dental, 751). Eighty-six percent of the medical
      practices [75/87, mean referral = 18.7 (SD = 17.9), range 0-105] and dental
      practices [43/50, mean referral = 15.0 (SD = 10.5), range 0-38] had e-referred.
      Of those smokers e-referred, 25.3 registered [mean smoker registration rate
      medical 4.9 (SD = 7.6, range 0-59), dental 3.6 (SD = 3.0, range 0-10)]. Estimated
      mean implementation costs are medical practices, US$429.00 (SD = 85.3); and
      dental practices, US$238.75 (SD = 13.6). High performing practices reported
      specific strategies to integrate ReferASmoker.org; low performers reported lack
      of smokers and patient disinterest in the study. Thus, a majority of practices e
      referred and 25.3 % of referred smokers registered demonstrating e-referral
      feasibility. However, further examination of the identified implementation
      barriers is important as of the estimated 90,000 to 140,000 smokers seen in the
      87 medical practices in 6 months, only 1,625 were e-referred. 

PMID- 24294326
TI  - Psychometric assessment of the Primary Care Behavioral Health Provider Adherence
      Questionnaire (PPAQ).
AB  - Adherence to protocol among behavioral health providers working in co-located,
      collaborative care or Primary Care Behavioral Health settings has rarely been
      assessed due to limited measurement options. Development of psychometrically
      sound measures of provider fidelity may improve the translation of these service
      delivery models into every day practice. One hundred seventy-three integrated
      behavioral health providers in VA primary care clinics responded to an online
      questionnaire to assess the reliability and validity of the Primary Care
      Behavioral Health Provider Adherence Questionnaire (PPAQ). Psychometric
      assessment resulted in a reliable 48-item measure with two subscales that
      specified essential and prohibited provider behaviors. The PPAQ demonstrated
      strong convergent and divergent validity when compared to another measure of
      health care integration. Known-group comparisons provided partial support for
      criterion validity. The PPAQ is a reliable and valid self-report of behavioral
      health provider fidelity with implications for improving provider training,
      program monitoring, and clinical research. 

PMID- 24294327
TI  - A systematic review of eHealth cancer prevention and control interventions: new
      technology, same methods and designs?
AB  - There has been a recent surge of eHealth programs in cancer and other content
      areas, but few reviews have focused on the methodologies and designs employed in
      these studies. We conducted a systematic review of studies on eHealth
      interventions on cancer prevention and control published between 2001 and 2010
      applying the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria
      and external validity components from the Reach Effectiveness Adoption
      Implementation Maintenance (RE-AIM) framework. We identified 113 studies that
      focused on cancer prevention and control of eHealth interventions. Most studies
      fell midway along the explanatory/pragmatic trial continuum, but few reported on
      various practical feasibility criteria for translation. Despite vast interest in
      cancer eHealth and the applied nature of this field, few studies considered key
      external validity issues. There is a need for use of alternative pragmatic study
      designs and transparent reporting of external validity components to produce more
      rapid and generalizable results. 

PMID- 24294328
TI  - HCI and mobile health interventions: How human-computer interaction can
      contribute to successful mobile health interventions.
AB  - Advances in mobile computing offer the potential to change when, where, and how
      health interventions are delivered. Rather than relying on occasional in-clinic
      interactions, mobile health (mHealth) interventions may overcome constraints due
      to limited clinician time, poor patient adherence, and inability to provide
      meaningful interventions at the most appropriate time. Technological capability,
      however, does not equate with user acceptance and adoption. How then can we
      ensure that mobile technologies for behavior change meet the needs of their
      target audience? In this paper, we argue that overcoming acceptance and adoption
      barriers requires interdisciplinary collaborations, bringing together not only
      technologists and health researchers but also human-computer interaction (HCI)
      experts. We discuss the value of human-computer interaction research to the
      nascent field of mHealth and demonstrate how research from HCI can offer
      complementary insights on the creation of mobile health interventions. We
      conclude with a discussion of barriers to interdisciplinary collaborations in
      mobile health and suggest ways to overcome them. 

PMID- 24294330
TI  - Translation of a comprehensive health behavior intervention for women living with
      HIV: the SMART/EST Women's Program.
AB  - Translation of behavioral interventions into community settings for people living
      with HIV/AIDS can decrease the risk of comorbid conditions. This study was
      designed to determine whether a multiple health behavior intervention for women
      with HIV/AIDS could be effectively translated into community health centers
      (CHCs), delivered by CHC primary care staff. Health Resources and Services
      Administration-supported CHCs in Miami, FL, and the New York metropolitan area
      participated. Six health behavior domains were assessed at baseline, 6 months,
      and 12 months post-intervention: nutrition, physical activity, sexual risk
      behavior, alcohol use, drug use, and tobacco use. Behavioral outcomes were
      compared between research staff-led and CHC staff-led intervention groups.
      Research staff and CHC staff outcomes were similar for the majority of outcomes.
      Results indicate that complex, multicomponent behavioral interventions can be
      translated into community-based settings with existing CHC staff and can produce
      clinical effects similar to those achieved by research staff. 

PMID- 24294329
TI  - mHealth approaches to child obesity prevention: successes, unique challenges, and
      next directions.
AB  - Childhood obesity continues to be a significant public health issue. mHealth
      systems offer state-of-the-art approaches to intervention design, delivery, and
      diffusion of treatment and prevention efforts. Benefits include cost
      effectiveness, potential for real-time data collection, feedback capability,
      minimized participant burden, relevance to multiple types of populations, and
      increased dissemination capability. However, these advantages are coupled with
      unique challenges. This commentary discusses challenges with using mHealth
      strategies for child obesity prevention, such as lack of scientific evidence base
      describing effectiveness of commercially available applications; relatively
      slower speed of technology development in academic research settings as compared
      with industry; data security, and patient privacy; potentially adverse
      consequences of increased sedentary screen time, and decreased focused attention
      due to technology use. Implications for researchers include development of more
      nuanced measures of screen time and other technology-related activities, and
      partnering with industry for developing healthier technologies. Implications for
      health practitioners include monitoring, assessing, and providing feedback to
      child obesity program designers about users' data transfer issues, perceived
      security and privacy, sedentary behavior, focused attention, and maintenance of
      behavior change. Implications for policy makers include regulation of claims and
      quality of apps (especially those aimed at children), supporting standardized
      data encryption and secure open architecture, and resources for research-industry
      partnerships that improve the look and feel of technology. Partnerships between
      academia and industry may promote solutions, as discussed in this commentary. 

PMID- 24294331
TI  - Healthy eating for life: rationale and development of an English as a second
      language (ESL) curriculum for promoting healthy nutrition.
AB  - Low health literacy contributes significantly to cancer health disparities
      disadvantaging minorities and the medically underserved. Immigrants to the United
      States constitute a particularly vulnerable subgroup of the medically
      underserved, and because many are non-native English speakers, they are pre
      disposed to encounter language and literacy barriers across the cancer continuum.
      Healthy Eating for Life (HE4L) is an English as a second language (ESL)
      curriculum designed to teach English language and health literacy while promoting
      fruit and vegetable consumption for cancer prevention. This article describes the
      rationale, design, and content of HE4L. HE4L is a content-based adult ESL
      curriculum grounded in the health action process approach to behavior change. The
      curriculum package includes a soap opera-like storyline, an interactive student
      workbook, a teacher's manual, and audio files. HE4L is the first teacher
      administered, multimedia nutrition-education curriculum designed to reduce cancer
      risk among beginning-level ESL students. HE4L is unique because it combines adult
      ESL principles, health education content, and behavioral theory. HE4L provides a
      case study of how evidence-based, health promotion practices can be implemented
      into real-life settings and serves as a timely, useful, and accessible nutrition
      education resource for health educators. 

PMID- 24294332
TI  - Peer-delivered physical activity interventions: an overlooked opportunity for
      physical activity promotion.
AB  - The purpose of this systematic review was to catalogue and synthesize published
      studies that have examined the effects of peer-delivered physical activity
      interventions on physical activity behavior. Ten published studies were
      identified that met the inclusion criteria. The following information was
      extracted from each study: study design and duration; characteristics of the
      sample, peers, and interventions; and physical activity outcomes. In all articles
      reporting within-groups analyses, peer-delivered interventions led to increases
      in physical activity behavior. When compared to alternatives, peer-delivered
      interventions were just as effective as professionally delivered interventions
      and more effective than control conditions for increasing physical activity. Only
      three studies included measures of social cognitive variables, yielding some
      evidence that peers may enhance self-efficacy and self-determined forms of
      motivation. Based on these findings, interventionists are encouraged to include
      peer mentors in their intervention delivery models. Investigators are encouraged
      to pursue a more comprehensive understanding of factors that can explain and
      maximize the impact of peer-delivered activity interventions. 

PMID- 24294333
TI  - Dynamics of the semantic priming shift: behavioral experiments and cortical
      network model.
AB  - Multiple semantic priming processes between several related and/or unrelated
      words are at work during the processing of sequences of words. Multiple priming
      generates rich dynamics of effects depending on the relationship between the
      target word and the first and/or second prime previously presented. The
      experimental literature suggests that during the on-line processing of the
      primes, the activation can shift from associates to the first prime to associates
      to the second prime. Though the semantic priming shift is central to the on-line
      and rapid updating of word meanings in the working memory, its precise dynamics
      are still poorly understood and it is still a challenge to model how it functions
      in the cerebral cortex. Four multiple priming experiments are proposed that cross
      manipulate delays and association strength between the primes and the target.
      Results show for the first time that association strength determines complex
      dynamics of the semantic priming shift, ranging from an absence of a shift to a
      complete shift. A cortical network model of spike frequency adaptive neuron
      populations is proposed to account for the non-continuous evolution of the
      priming shift over time. It allows linking the dynamics of the priming shift
      assessed at the behavioral level to the non-linear dynamics of the firing rates
      of neurons populations. 

PMID- 24294334
TI  - Identifying type I excitability using dynamics of stochastic neural firing
      patterns.
AB  - The stochastic firing patterns are simulated near saddle-node bifurcation on an
      invariant cycle corresponding to type I excitability in stochastic Morris-Lecar
      model. In absence of external periodic signal, the stochastic firing manifests
      continuous distribution in ISI histogram (ISIH), whose amplitude at first
      increases sharply and then decreases exponentially. In presence of the external
      periodic signal, stochastic firing patterns appear as two cases of integer
      multiple firing with multiple discrete peaks in ISIH. One manifests perfect
      exponential decay in all peaks and the other imperfect exponential decay except a
      lower first peak. These stochastic firing patterns simulated with or without
      external periodic signal can be demonstrated in the experiments on rat
      hippocampal CA1 pyramidal neurons. The exponential decay laws in the multiple
      peaks are also acquired using probability analysis method. The perfect decay law
      is determined by the independent characteristic within the firing while the
      imperfect decay law is from the inhibitory effect. In addition, the stochastic
      firing patterns corresponding to type I excitability are compared to those of
      type II excitability. The results not only reveal the dynamics of stochastic
      firing patterns with or without external signal corresponding to type I
      excitability, but also provide practical indicators to availably identify type I
      excitability. 

PMID- 24294335
TI  - Combined effects of LTP/LTD and synaptic scaling in formation of discrete and
      line attractors with persistent activity from non-trivial baseline.
AB  - In this article, we analyze combined effects of LTP/LTD and synaptic scaling and
      study the creation of persistent activity from a periodic or chaotic baseline
      attractor. The bifurcations leading to the creation of new attractors have been
      detailed; this was achieved using a mean field approximation. Attractors encoding
      persistent activity can notably appear via generalized period-doubling
      bifurcations, tangent bifurcations of the second iterates or boundary crises,
      after which the basins of attraction become irregular. Synaptic scaling is shown
      to maintain the coexistence of a state of persistent activity and the baseline.
      According to the rate of change of the external inputs, different types of
      attractors can be formed: line attractors for rapidly changing external inputs
      and discrete attractors for constant external inputs. 

PMID- 24294336
TI  - A new discriminant NMF algorithm and its application to the extraction of subtle
      emotional differences in speech.
AB  - In this study we propose a new feature extraction algorithm, dNMF (discriminant
      non-negative matrix factorization), to learn subtle class-related differences
      while maintaining an accurate generative capability. In addition to the minimum
      representation error for the standard NMF (non-negative matrix factorization)
      algorithm, the dNMF algorithm also results in higher between-class variance for
      discriminant power. The multiplicative NMF learning algorithm has been modified
      to cope with this additional constraint. The cost function was carefully designed
      so that the extraction of feature coefficients from a single testing pattern with
      pre-trained feature vectors resulted in a quadratic convex optimization problem
      in non-negative space for uniqueness. It also resolves issues related to the
      previous discriminant NMF algorithms. The developed dNMF algorithm has been
      applied to the emotion recognition task for speech, where it needs to emphasize
      the emotional differences while de-emphasizing the dominant phonetic components.
      The dNMF algorithm successfully extracted subtle emotional differences,
      demonstrated much better recognition performance and showed a smaller
      representation error from an emotional speech database. 

PMID- 24294337
TI  - Investigation of changes in EEG complexity during memory retrieval: the effect of
      midazolam.
AB  - The aim of this study is applying nonlinear methods to assess changes in brain
      dynamics in a placebo-controlled study of midazolam-induced amnesia. Subjects
      injected with saline and midazolam during study, performed old/new recognition
      memory tests with EEG recording. Based on previous studies, as midazolam causes
      anterograde amnesia, we expected that midazolam would affect the EEG's degree of
      complexity. Recurrence quantification analysis, and approximate entropy were used
      in this assessment. These methods compare with other nonlinear techniques such as
      computation of the correlation dimension, are suitable for non-stationary EEG
      signals. Our findings suggest that EEG's complexity decreases during memory
      retrieval. Although this trend is observed in nonlinear curves related to the
      midazolam condition, the overall complexity were greater than in the saline
      condition. This result implies that impaired memory function caused by midazolam
      is associated with greater EEG's complexity compared to normal memory retrieval
      in saline injection. 

PMID- 24294338
TI  - Predictive adjustment of the perceived direction of gaze during saccadic eye
      movements.
AB  - When we look at a stationary object, the perceived direction of gaze (where we
      are looking) is aligned with the physical direction of eyes (where our eyes are
      oriented) by which the object is foveated. However, this alignment may not hold
      in a dynamic situation. Our experiments assessed the perceived locations of two
      brief stimuli (1 ms) simultaneously displayed at two different physical locations
      during a saccade. The first stimulus was in the instantaneous location to which
      the eyes were oriented and the second one was always in the same location as the
      initial fixation point. When the timing of these stimuli was changed intra
      saccadically, their perceived locations were dissociated. The first stimuli were
      consistently perceived near the target that will be foveated at saccade
      termination. The second stimuli once perceived near the target location, shifted
      in the direction opposite to that of saccades, as its latency from saccades
      increased. These results suggested an independent adjustment of gaze orientation
      from the physical orientation of eyes during saccades. The spatial dissociation
      of two stimuli may reflect sensorimotor control of gaze during saccades. 

PMID- 24294339
TI  - Analysis of the multicopper oxidase gene regulatory network of Aeromonas
      hydrophila.
AB  - Multicopper oxidase (MCO) is an enzyme which involves in reducing the oxygen in a
      four electron reduction to water with concomitant one electron oxidation of
      reducing the substrate. We have generated the 3-D structure of MCO by homology
      modeling and validated on the basis of free energy while 90.4 % amino acid
      residues present in allowed regions of Ramachandran plot. The screening of
      potential hazardous aromatic compounds for MCO was performed using molecular
      docking. We obtained Sulfonaphthal, Thymolphthalein, Bromocresol green and
      Phloretin derivatives of phenol and aromatic hydrocarbon were efficient
      substrates for MCO. The phylogeny of MCO reveals that other bacteria restrain the
      homologous gene of MCO may play an important role in biodegradation of aromatic
      compounds. We have demonstrated the gene regulatory network of MCO with other
      cellular proteins which play a key role in gene regulation. These findings
      provide a new insight for oxidization of phenolic and aromatic compounds using
      biodegradation process for controlling environmental pollution. 

PMID- 24294340
TI  - Optimizing bioethanol production by regulating yeast growth energy.
AB  - The goal of this work is to optimize production of bio-ethanol by fermentation
      through regulating yeast growth energy (YGE), and provide the mechanism of
      ethanol production from food-waste leachate (FWL) using yeast (S. cerevisiae) as
      inoculums to be predictable and controllable. The wide range of reduced sugar
      concentration (RSC) which is commonly administered from low (35 g per liter) to
      very high (100 g per liter) is responsible for costs increasing besides risks of
      FWL contamination and death of yeast cells. A mathematical model is presented to
      describe yeast growth energy (YGE) due to RSC doses along with predicting the
      amounts of ethanol yield by each dose to identify the optimum one. Simulations of
      the presented model showed that YGE, energy intake (EI), and their produced
      ethanol energy (PEE) are always balanced during fermentation process according to
      the law of conservation of energy. For a better fermentation rate in a continuous
      process and a large-scale production; YGE should be less than half of EI and more
      than its quarter (i.e. [Formula: see text]) which keeps the residual energy less
      than YGE to avoid risks of osmotic stresses or aging of cells allowing the
      survival of all yeast cells as long as possible to maximize ethanol production
      and decrease productivity costs. 

PMID- 24294341
TI  - Gene regulatory network modeling using literature curated and high throughput
      data.
AB  - Building on the linear matrix inequality (LMI) formulation developed recently by
      Zavlanos et al. (Automatica: Special Issue Syst Biol 47(6):1113-1122, 2011), we
      present a theoretical framework and algorithms to derive a class of ordinary
      differential equation (ODE) models of gene regulatory networks using literature
      curated data and microarray data. The solution proposed by Zavlanos et al.
      (Automatica: Special Issue Syst Biol 47(6):1113-1122, 2011) requires that the
      microarray data be obtained as the outcome of a series of controlled experiments
      in which the network is perturbed by over-expressing one gene at a time. We note
      that this constraint may be relaxed for some applications and, in addition,
      demonstrate how the conservatism in these algorithms may be reduced by using the
      Perron-Frobenius diagonal dominance conditions as the stability constraints. Due
      to the LMI formulation, it follows that the bounded real lemma may easily be used
      to make use of additional information. We present case studies that illustrate
      how these algorithms can be used on datasets to derive ODE models of the
      underlying regulatory networks. 

PMID- 24294342
TI  - Are we doing synthetic biology?
AB  - Synthetic Biology is a singular, revolutionary scenario with a vast range of
      practical applications but, is SB research really based on engineering
      principles? Is it contributing to the artificial synthesis of life or using
      approaches "sophisticated" enough to fall outside the scope of biotechnology or
      metabolic engineering? We have reviewed the state of the art on synthetic biology
      and we conclude that most research projects actually describe an extension of
      metabolic engineering. We draw this conclusion because the complexity of living
      organisms, their tight dependence on evolution and our limited knowledge of the
      interactions between the molecules they are made of, actually make life difficult
      to engineer. We therefore propose the term synthetic biology should be used more
      sparingly. 

PMID- 24294343
TI  - Interventional musculoskeletal US: an update on materials and methods.
AB  - Pain is one of the most common causes of reduced productivity. The annual cost of
      health-related reductions in productivity has been estimated at approximately 225
      billion dollars in the United States alone. Ultrasound-guided locoregional
      infiltration procedures have frequently been shown to offer economical,
      effective, lasting relief of pain. In-depth familiarity with the equipment
      (probes and needles) and techniques used to perform these procedures are
      fundamental for safe, effective treatment. In fact, depending on the
      characteristics of the patient and the clinical problem, the approach and
      technique may have to be modified to simplify the procedure and ensure better
      results. Up-to-date knowledge of the drugs used for these infiltrations
      (indications, how they are used) is equally important. Our aim is to provide an
      update on the techniques and materials used in interventional musculoskeletal
      ultrasonography based on a review of the most recent literature as well as on our
      personal experience. 

PMID- 24294344
TI  - Hemodynamic classification of varicoceles in men: our experience.
AB  - AIM: The aim of this work is to propose a new hemodynamic classification of male
      varicoceles that can improve the accuracy of staging and the quality of the
      examination report. We retrospectively analyzed data on outpatients referred to
      our vascular ultrasonography service by general practitioners or urologists for
      work-up of "varicoceles." Quantification and characterization of venous reflux is
      essential for selecting patients who require treatment and for evaluating the
      latter's effectiveness, as demonstrated by our experience in a subgroup of 58
      patients referred for imaging after surgery on endovascular procedures. MATERIALS
      AND METHODS: We performed scrotal Doppler sonography on 278 males seen during the
      period 2009-2011 for doubts raised during clinical assessment of varicoceles or
      for postoperative evaluation of residual reflux. RESULTS: The diagnosis of
      varicocele was confirmed on 193 subjects; in 32 patients who had undergone
      percutaneous or surgical treatment the examination demonstrated the presence of
      residual reflux, while in 85 cases the presence of pain or a scrotal mass was not
      associated with venous reflux. CONCLUSIONS: Standardized instrumental criteria
      have been developed for the diagnosis of varicoceles but not for their staging.
      The classification system we propose provides a simple, hemodynamically accurate
      method for qualitatively evaluating venous reflux, and it can be a useful tool
      for verifying the success of surgical and endovascular procedures for correcting
      varicoceles.

PMID- 24294345
TI  - Focal splenic lesions: US findings.
AB  - Ultrasound (US) imaging of the spleen was considered of little use in the past
      and was performed only to distinguish between cystic and solid lesions. However,
      in the last decade due to experience acquired and the introduction of second
      generation contrast agents, this technique has been re-evaluated as contrast
      enhanced US (CEUS) allows detection and characterization of most focal lesions of
      the spleen with a high sensitivity and a good specificity. Gray-scale US presents
      a low specificity in splenic infarctions with a high rate of false negative
      cases, whereas specificity reaches 100 %, if the examination is performed using
      US contrast agents. Gray-scale US can provide a correct diagnosis in simple
      cysts, whereas CEUS is useful when cystic lymphangioma is suspected. In the study
      of splenic lesions, the most important problem is to differentiate between
      angioma, hamartoma, lymphoma, and metastasis. CEUS reaches a good specificity in
      the differentiation of benign from malignant splenic lesions, as hypo-enhancement
      in the parenchymal phase is predictive of malignancy in 87 % of cases. In
      conclusion, Gray-scale US and particularly CEUS are at present widely indicated
      in the study of focal splenic lesions. 

PMID- 24294346
TI  - Pitfalls of contrast-enhanced ultrasound (CEUS) in the diagnosis of splenic
      sarcoidosis.
AB  - By observing the real-time behavior of focal liver lesions at three vascular
      phases (arterial, portal-venous, and late), contrast-enhanced ultrasound (CEUS)
      has been successfully applied to differentiate benign from malignant hepatic
      nodules. In recent years, numerous studies highlighted the usefulness of CEUS
      also for other applications such as abdominal trauma, renal, pancreatic, thyroid,
      and inflammatory bowel diseases, supporting its role even in differentiating
      benign from malignant splenic nodules. Therefore, the European Federation of
      Societies for Ultrasound in Medicine and Biology (EFSUMB) recently updated the
      guidelines for the use of ultrasound contrast agents in clinical practice,
      pointing out the indication to characterize splenic parenchymal inhomogeneity or
      suspected lesions found on conventional ultrasound (BUS). We describe the case of
      a patient with a history of colon cancer and finding, at BUS and CEUS, of
      hypoechoic lesions with a highly suggestive pattern for metastases, subsequently
      histologically proved to be splenic localizations of a benign and multisystemic
      granulomatous disease such as sarcoidosis. We therefore reviewed the current
      literature focusing on the role of CEUS in differentiating benign from malignant
      splenic lesions, emphasizing on the lack of data and numerical shortage of
      sarcoidosis derived-lesions in the available studies. We conclude that
      sarcoidosis remains a diagnosis of exclusion and new studies are needed before
      defining precise indications of CEUS in these patients. 

PMID- 24294347
TI  - Testicular adrenal rest tissue in a patient with classical congenital adrenal
      hyperplasia: color Doppler findings.
AB  - Congenital adrenal hyperplasia (also known as congenital adrenogenital syndromes)
      refers to a group of autosomal recessive diseases characterized by altered
      cortisol production, which may be associated with aldosterone deficiency. The
      absence of cortisol synthesis stimulates corticotropin production by the adrenal
      cells and the accumulation of cortisol precursors, which will be diverted for the
      production of sex hormones. In affected males, ectopic adrenal tissue frequently
      develops, usually at the testicular level. This tissue is absolutely identical to
      that of the adrenal gland itself, and its functionality can be stimulated by ACTH
      and suppressed with glucocorticoid therapy. The authors report the case of a male
      patient with classic congenital adrenal hyperplasia, who was referred to our
      staff for evaluation of bilateral testicular tenderness and enlargement. Color
      Doppler sonography revealed mild enlargement of both gonads, widespread
      disruption of the testicular echostructure, and hypervascularization. Two months
      later, when the underlying disease had been controlled, repeat color Doppler
      ultrasonography revealed markedly decreased vascularity, although no change was
      noted on the B-mode examination. The color Doppler findings thus represent an
      early indicator of response to treatment. 

PMID- 24294348
TI  - Testicular neuroblastoma.
AB  - We report a case of isolated intratesticular neuroblastoma in a 17-year-old boy
      with a history of recurrent metastatic neuroblastoma. He had undergone multiple
      cycles of chemotherapy, and at the time of our examination was apparently disease
      free. Testicular metastases are not uncommon in patients with active metastatic
      neuroblastoma, but isolated testicular involvement is rare. In this case,
      ultrasound follow-up allowed early diagnosis and prompt treatment of the
      testicular lesion. At the 18-month follow-up visit, the patient remains disease
      free. 

PMID- 24294349
TI  - Intralesional hemorrhage in Krukenberg tumor: a case report and review of the
      literature.
AB  - Acute abdomen due to female genital apparatus disease is very rare. Most are due
      to intralesional effusion of benign tumors. The authors present a 40-year-old
      woman with acute abdomen pain due to haemorrhagic ovarian metastasis of
      colorectal cancer, focusing on the role of imaging to get the management of the
      patient. 

PMID- 24294350
TI  - Urinary tract disease in dogs: US findings. A mini-pictorial essay.
AB  - Ultrasound (US) is the most commonly used imaging method for studying urinary
      tract disorders in dogs, as it is easy to perform, inexpensive and provides
      excellent contrast resolution in real-time. However, US examination of dogs
      presents a series of technical difficulties, and the US operator must therefore
      have a longstanding experience and access to high-quality equipment including a
      range of different probes to achieve a correct diagnosis. The aim of this mini
      pictorial essay is to describe US findings and patterns which permit
      identification of the most common pathologies of the urinary tract in dogs. The
      technical difficulties that may be encountered are also evaluated as well as
      integration with other imaging modalities (traditional X-ray, computed
      tomography, magnetic resonance imaging). 

PMID- 24294351
TI  - Functional MRI demonstrates pain perception in hand osteoarthritis has features
      of central pain processing.
AB  - BACKGROUND: Hand osteoarthritis (HOA) is typified by pain and reduced function.
      We hypothesised that people with HOA have enhanced sensitivity and activation of
      peripheral nociceptors in the hand, thereby potentiating chronic pain. In our
      study we aimed to assess if central sensitisation mediates pain perception in
      osteoarthritis of the hand. METHODS: Participants with proximal and distal
      interphalangeal joint (PIP/DIP) HOA and non-OA controls were recruited. Clinical
      pain scores using the visual analogue scale (VAS) were recorded before and after
      performing a painful hand task. Central pain processing was evaluated with
      functional brain neuroimaging (fMRI) using a finger flexion-extension (FFE) task
      performed over 3 minutes. Data was analysed with FMRIB software
      (www.fmrib.ox.ac.uk/fsl). Group mean activation of functional MRI signal between
      hand osteoarthritis and control non-arthritic participants was compared. RESULTS:
      Our group of hand OA participants reported high pain levels compared with non
      arthritic controls as demonstrated by the mean VAS in hand OA participants of
      59.31+/- 8.19 mm compared to 4.00 +/- 1.89 mm in controls (p < 0.0001), despite
      all participants reporting analgesic use. Functional MRI analysis showed
      increased activation in the thalamus, cingulate, frontal and somatosensory cortex
      in the hand OA group but not in controls (thresholded at p < 0.05). Regions of
      activation were mapped to Brodmann areas 3, 4, 6, 9, 13, 22, 24 and 44. Activated
      regions found in our study are recognised higher brain pain processing centres
      implicated in central sensitisation. CONCLUSIONS: People with hand osteoarthritis
      demonstrated features of central sensitisation that was evident after a finger
      flexion-extension task using functional MRI. Functional MRI is a useful biomarker
      in detecting pain in hand osteoarthritis and could be used in future hand
      osteoarthritis pain studies to evaluate pain modulation strategies.

PMID- 24294352
TI  - Effects and interactions of MiR-577 and TSGA10 in regulating esophageal squamous
      cell carcinoma.
AB  - Testis specific 10 (TSGA10) was originally identified as a testis-specific
      protein and tumor-associated antigen in a number of cancer types. In this study,
      we found that down-regulation of TSGA10 was associated with increased malignancy
      and clinical features of esophageal squamous cell carcinomas (ESCCs). Moreover,
      increased expression of TSGA10 inhibited, while its knockdown promoted, tumor
      formation in vivo in nude mice. At the 3'UTR of the TSGA10 gene we identified two
      binding sites for microRNA-577 (miR-577). Further investigation demonstrated that
      expression levels of miR-577 and TSGA10 were negatively correlated to each other
      in ESCC cell lines and tumor samples. Moreover, manipulation of miR-577 and
      TSGA10 expression confirmed that miR-577 can regulate TSGA10 and in turn affect
      cell proliferation in vitro. Additionally, with flow cytometry and manipulation
      of the mir-577/TSGA10 axis, it was found that mir-577/TSGA10 axis influenced the
      growth of ESCC through regulating the G1-S phase transition. We also obtained
      evidence to establish that mir-577/TSGA10 axis activation was always accompanied
      by inactivation of the p53 pathway or the Rb pathway or both, thus, the latter
      two pathways are obligatory for progression of ESCCs with mir-577/TSGA10 axis
      activation. In addition, we found that such an interactive pathway in regulating
      cancer cell proliferation was restricted to a few cancer types including ESCC,
      but not uniformly applicable to other cancer types. This newly discovered
      regulatory mechanism provides a new dimension for ESCC diagnosis and therapy. 

PMID- 24294354
TI  - The missing puzzle piece: splicing mutations.
AB  - Proper gene splicing is highly dependent on the correct recognition of exons.
      Among the elements allowing this process are the "cis" (conserved sequences) and
      "trans" (snRNP, splicing factors) elements. Splicing mutations are related with a
      number of genetic disorders and usually induce exon skipping, form new
      exon/intron boundaries or activate new cryptic exons as a result of alterations
      at donor/acceptor sites. They constitute more than 9% of the currently published
      mutations, but this value is highly underestimated as many of the potential
      mutations are located in the "cis" elements and should be confirmed
      experimentally. The most commonly detected splicing mutations are located at
      donor (5') and acceptor (3') sites. Mutations at the branch point are rare (only
      over a dozen are known to date), and are mostly searched and detected when no
      alteration has been detected in the sequenced exons and UTRs. Polypyrimidine
      tract mutations are equally rare. High throughput technologies, as well as
      traditional Sanger sequencing, allow detection of many changes in intronic
      sequences and intron/exon boundaries. However, the assessment whether a mutation
      affects exon recognition and results in a genetic disorder has to be conducted
      using molecular biology methods: in vitro transcription of the sequence of
      interest cloned into a plasmid, with and without alterations, or mutation
      analysis via a hybrid minigene system. Even though microarrays and new generation
      sequencing methods pose difficulties in detecting novel branch point mutations,
      these tools seem appropriate to expand the mutation detection panel especially
      for diagnostic purposes. 

PMID- 24294353
TI  - Regulatory T cells and B cells: implication on autoimmune diseases.
AB  - The regulatory T (Treg) cells play an important role in the maintenance of
      homeostasis and the prevention of autoimmune diseases. Although most studies are
      focusing on the role of Treg cells in T cells and T cells-mediated diseases,
      these cells also directly affect B cells and other non-T cells. This manuscript
      updates the role of Treg cells on the B cells and B cell-mediated diseases. In
      addition, the mechanisms whereby Treg cells suppress B cell responses have been
      discussed. 

PMID- 24294355
TI  - Morphological and functional characterization of non-alcoholic fatty liver
      disease induced by a methionine-choline-deficient diet in C57BL/6 mice.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic
      steatohepatitis (NASH), appears to be increasingly common worldwide. Its
      histopathology and the effects of nutrition on liver function have not been fully
      determined. AIM: To elucidate the cellular mechanisms of NAFLD induced by a
      methionine-choline-deficient (MCD) diet in mice. Particular focus was placed on
      the role of phagocytic cells. METHODS: Male C57BL/6 mice were fed an MCD diet for
      30 weeks. A recovery model was also established wherein a normal control diet was
      provided for 2 weeks after a period of 8, 16, or 30 weeks. RESULTS: Mice fed the
      MCD diet for >= 2 weeks exhibited severe steatohepatitis with elevated serum
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.
      Steatohepatitis was accompanied by the infiltration of CD68-positive macrophages
      (Kupffer cells). The severity of steatohepatitis increased in the first 16 weeks
      but was seen to lessen by week 30. Fibrosis began to develop at 10 weeks and
      continued thereafter. Steatohepatitis and elevated serum hepatic enzyme
      concentrations returned to normal levels after switching the diet back to the
      control within the first 16 weeks, but fibrosis and CD68-positive macrophages
      remained. CONCLUSIONS: The histopathological changes and irreversible fibrosis
      seen in this model were caused by prolonged feeding of an MCD diet. These results
      were accompanied by changes in the activity of CD68-positive cells with temporary
      elevation of CCL-2, MMP-13, and MMP-9 levels, all of which may trigger early
      steatohepatitis and late fibrosis through phagocytosis-associated MMP induction.

PMID- 24294356
TI  - Effects of industrial noise on circumpulpar dentin--a field emission scanning
      electron microscopy and energy dispersive spectroscopy analysis.
AB  - Chronic exposure to Industrial Noise (IN), rich in Low Frequency Noise (LFN),
      causes systemic fibrotic transformation and sustained stress. Dental wear,
      significantly increased with exposure to LFN, affects the teeth particularly
      through the circumpulpar dentin. Our goal is to understand the consequences of IN
      exposure on the circumpulpar dentin of Wistar rats. 10 Wistar rats were exposed
      to IN for 4 months, according to an occupationally simulated time schedule and 10
      animals were used as age-matched controls. The first and the second upper and
      lower molars of each animal were processed for observation by Field Emission
      Scanning Electron Microscopy (FESEM) and Energy Dispersive Spectroscopy (EDS)
      analysis was performed. In exposed animals FESEM showed a 2.0 to 6.0 MUm-dense
      mineral band between dentin and the pulp with no regular continuity with the
      tubules. This structure had a few tubules where the odontoblasts processes could
      be observed embedded within the band and collagen fibers were trapped inside. EDS
      analysis revealed that it was hydroxyapatite similar to dentin, with a higher
      carbon content. FESEM results show that the band may be tertiary reparative
      dentin formed by odontoblast-like cells, but the increased amount of carbon (EDS)
      could mean that it is sclerotic dentin. IN should be acknowledge as a strong
      stimulus, able to cause an injury to odontoblasts and to the formation of
      reparative tertiary dentin, in a process that may accelerate the aging of the
      teeth, either by direct impact of acoustic pressure pulsations or by increased
      stress and dental wear. 

PMID- 24294357
TI  - Therapeutic effect of human umbilical cord-derived mesenchymal stem cells in rat
      severe acute pancreatitis.
AB  - AIM: To investigate the therapeutic effect of umbilical cord-derived mesenchymal
      stem cells (UC-MSCs) on rat severe acute pancreatitis (SAP). METHODS: Rats were
      randomly divided into three groups (n = 15 per group): control group, SAP group,
      and SAP+MSCs group. SAP was established by retrograde pancreatic duct injection
      of 3% sodium taurocholate. In SAP+MSCs group, UC-MSCs at 1 * 10(7) cells/kg were
      injected via the tail vein 12 h after SAP. Rats (n = 5 per group) were sacrificed
      on days 1, 3 and 5, and the blood and pancreatic tissues were collected. The
      levels of serum amylase, lipase, inflammatory cytokines, and anti-inflammatory
      cytokines were determined. Pathological changes of the pancreas (HE staining) and
      apoptotic acinar cells (TUNEL staining) were observed under light microscope.
      RESULTS: The levels of serum amylase and lipase in SAP group were significantly
      higher than those in control group (P<0.05). The pancreas in SAP group showed
      significantly massive edema, inflammation, hemorrhage and necrosis when compared
      with control group. There were numerous TUNEL-positive apoptotic acinar cells
      after SAP. However, in SAP+MSCs group, the levels of serum amylase were
      significantly reduced on days 1, 3, and 5 after MSC transplantation (P<0.01). The
      serum lipase level in SAP+MSCs group was significantly lower than that in SAP
      group on days 3 and 5 (P<0.01). The edema formation, inflammatory cell
      infiltration, hemorrhage, and necrosis were reduced significantly attenuated in
      SAP+MSCs group as compared to SAP group (P<0.05). MSCs significantly reduced the
      levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), but
      increased the levels of anti-inflammatory cytokines (IL-4 and IL-10) in SAP rats.
      The number of TUNEL-positive acinar cells was significantly reduced on days 3 and
      5 after MSCs transplantation (P<0.01). CONCLUSION: Transplantation of UC-MSCs
      significantly inhibits inflammation and decreases pancreatic injury secondary to
      SAP.

PMID- 24294358
TI  - Various tumors in the nasal vestibule.
AB  - Various types of diseases can involve the nasal vestibule. Diagnosis and
      treatment of a nasal vestibular mass is often challenging due to the anatomical
      features of the nasal vestibule. Here, we present four cases with nasal
      vestibular masses. Two cases were diagnosed as squamous papillomas. The others
      were a trichofolliculoma and pseudoepitheliomatous hyperplasia with
      hyperkeratosis. Our aim was to discuss the characteristics of each disease and
      the considerations thought to be necessary for diagnosis and treatment of nasal
      vestibular tumors from these cases and the related literature. 

PMID- 24294359
TI  - Comparing the expression of integrins alphavbeta3, alphavbeta5, alphavbeta6,
      alphavbeta8, fibronectin and fibrinogen in human brain metastases and their
      corresponding primary tumors.
AB  - AIMS: To evaluate the expression of alphav-series integrins in brain metastases.
      Inhibitors targeting these integrins are being tested for their therapeutic
      potential. MATERIAL AND METHOD: The extracellular regions of the alphavbeta3,
      alphavbeta5, alphavbeta6, alphavbeta8, the cytoplasmic domain of beta3, the
      alphav-chain, and the ECM molecules fibronectin and fibrinogen were studied
      immunohistochemically in a series of 122 carcinoma and 60 melanomas metastatic to
      the central nervous system. In addition, 38 matched primary and metastatic tumors
      to the brain were compared directly. RESULTS: The alphav-subunit was generally
      moderately to highly expressed in most tumors. alphavbeta3 and cytoplasmic beta3
      were weakly to moderately detectable in metastatic renal cell carcinomas and
      melanomas, alphavbeta5 was prominently expressed in metastatic renal and
      colorectal carcinomas, alphavbeta6 was most abundantly detectable in metastatic
      lung adenocarcinomas, but absent in melanomas. The tumor associated vessels in
      CNS metastases consistently expressed alphavbeta3, alphavbeta5, alphav-,
      fibronectin and fibrinogen, however, mostly at low levels, while alphavbeta6,
      alphavbeta8 were lacking in vasculature. The comparative analysis of 38 matched
      primary tumors and brain metastases showed comparable levels of expression only
      for alphavbeta3 and alphavbeta8, while alphavbeta6 and alphavbeta5 were higher in
      primaries. CONCLUSION: We confirmed that integrin expression exhibits
      considerable heterogeneity according to tumor origin. alphavbeta5 is the most
      promising target for integrin targeted treatment in brain metastases.

PMID- 24294360
TI  - Deoxycytidine kinase promotes the migration and invasion of fibroblast-like
      synoviocytes from rheumatoid arthritis patients.
AB  - Rheumatoid arthritis (RA) is a complex, multi-system disease whose primary site
      of inflammatory tissue damage is the joint. The increasing evidences indicate
      that activated RA fibroblast-like synoviocytes (FLS) play a critical role in the
      development of pannus by migrating into cartilage and bone. Furthermore FLS and T
      cells can activate each other in vitro and in vivo, which is crucial for the
      progress of RA. Deoxycytidine kinase (DCK) has been linked to peripheral T cell
      homeostatic proliferation and survival, which is very important for RA. Yet, the
      function of DCK in FLS is still unknown. Here, we present a story that DCK could
      regulate the migration and invasion of FLS through AKT pathway in RA patients.
      Moreover, DCK seems to be the upstream of AKT and FAK, and AKT inhibitor exerted
      the similar effect on FLS motility. In summary, our study characterized the new
      role of DCK in human primary FLS cells, and figured out the possible pathway DCK
      involved in, and these findings might propose DCK as a novel target for
      controlling joint destruction of RA. 

PMID- 24294361
TI  - Potential biomarkers for paclitaxel sensitivity in hypopharynx cancer cell.
AB  - Paclitaxel has been proved to be active in treatment and larynx preservation of
      HNSCC, however, the fact that about 20-40% patients do not respond to paclitaxel
      makes it urgent to figure out the biomarkers for paclitaxel-based treatment in
      Hypopharynx cancer (HPC) patients to improve the therapy effect. In this work,
      Fadu cells, treated or untreated with low dose of paclitaxel for 24 h, were
      applied to DNA microarray chips. The differential expression in mRNAs and miRs
      was analyzed and the network between expression-altered mRNAs and miRs was
      constructed. Differentially expressed genes were mainly enriched in superpathway
      of cholesterol biosynthesis (ACAT2, MSMO1, LSS, FDFT1 and FDPS etc.), complement
      system (C3, C1R, C1S, CFR and CFB etc.), interferon signaling (IFIT1, IFIT3,
      IFITM1 and MX1 etc.), mTOR signaling (MRAS, PRKAA2, PLD1, RND3 and EIF4A1 etc.)
      and IGF1 signaling (MRAS, IGFBP7, JUN and FOS etc.), most of these pathways are
      implicated in tumorigenesis or chemotherapy resistance. The first three pathways
      were predicted to be suppressed, while the last two pathways were predicted to be
      induced by paclitaxel, suggesting the combination therapy with mTOR inhibition
      and paclitaxel might be better than single one. The dramatically expression
      altered miRs were miR-112, miR-7, miR-1304, miR-222*, miR-29b-1* (these five miRs
      were upregulated) and miR-210 (downregulated). The 26 putative target genes
      mediated by the 6 miRs were figured out and the miR-gene network was constructed.
      Furthermore, immunoblotting assay showed that ERK signaling in Fadu cells was
      active by low dose of paclitaxel but repressed by high dose of paclitaxel.
      Collectively, our data would provide potential biomarkers and therapeutic targets
      for paclitaxel-based therapy in HPC patients. 

PMID- 24294362
TI  - Development of neural stem cells at different sites of fetus brain of different
      gestational age.
AB  - OBJECTIVE: This study aimed to investigate the development of neural stem cells
      (NSCs) in fetal brain, which may provide experimental evidence for the clinical
      treatment of brain injury in children. METHODS: A total of 60 fetuses were
      collected after labor induction and divided into 6 groups according to the
      gestational age (16 w, 20 w, 24 w, 28 w, 32 w and 36 w; n=10 per group). The
      hippocampus, striatum, subventricular zone, frontal lobe, temporal lobe,
      occipital lobe and parietal lobe were harvested. In situ hybridization,
      immunohistochemistry and light microscopy were done to determine the morphology
      and quantity of NSCs. RESULTS: NSCs were identified in the brain of fetuses with
      different gestational age. NSCs were round, oval, spindle-shaped, starlike,
      triangular or polygonal. NSC colony was also observed with symmetrical or
      asymmetrical division. Single NSC, group-like NSCs and cluster-like NSCs were
      found in the different sites of fetal brain, and NCSs interacted with each other
      via synapses. However, the distribution, morphology, growth and quantity of NSCs
      were different in the brain of fetuses with different gestational age. The number
      of NSCs reduced with the increase in gestational age, but they were always
      observed. CONCLUSION: The morphology of NSCs in fetal brain is variable and they
      are widely distributed in the hippocampus, subventricular zone, striatum and
      cortex. The number of NSCs reduced with the increase of gestational age.

PMID- 24294363
TI  - Epstein-Barr virus infection correlates with the expression of COX-2, p16(INK4A)
      and p53 in classic Hodgkin lymphoma.
AB  - Classic Hodgkin lymphoma (cHL), a germinal-center related B cell neoplasm in
      almost all cases, is characterized by scarcity of the neoplastic Hodgkin/Reed
      Sternberg (H/RS) cells. Epstein-Barr virus (EBV) has been shown to affect cell
      cycle and regulation of apoptosis. In total, 95 cases of cHL were studied. Five
      micrometer sections were prepared and stained with hematoxylin and eosin and
      immunohistochemical streptavidin-biotin methods for EBV-LMP-1, COX-2, p53, p16,
      ki-67 and cleaved caspase-3. In-situ hybridization for EBV encoded RNA was used
      to confirm the detection of EBV in H/RS. There were 49 nodular sclerosis, 32
      mixed cellularity, 8 lymphocyte-rich, and 6 lymphocyte-depleted subtypes in this
      series of cases. EBV, COX-2, p16(INK4A) and p53 were detected in 55% (52/95), 64%
      (61/95), 62% (59/95), and 65% (62/95) of the cases respectively. EBV was detected
      in 62% (38/61), 70% (41/59), and 69% (43/62) of COX2, p16 and p53 positive cases
      respectively. On the other hand, EBV-non-infected cases of cHL are associated
      with 59% (20/34), 69% (25/36), and 73% (24/33) of COX2, p16 and p53 negative
      cases respectively. In conclusion, EBV infection is associated with the
      expression of COX-2, p16(INK4A) and p53. EBV might be the dominant factor in
      determining the expression of these three proteins. 

PMID- 24294364
TI  - Investigation of age-related changes in LMNA splicing and expression of progerin
      in human skeletal muscles.
AB  - Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina
      proteins lamin A/C, have not been investigated in skeletal muscle. In the rare
      premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo
      point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a
      150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform,
      progerin. The LMNA Delta150 progerin transcript has also been found in trace
      quantities in tissues of healthy people and its implication in 'natural' ageing
      has been proposed. We therefore investigated the expression of progerin and lamin
      A/C in normal human and mouse skeletal muscles of different ages. LMNA Delta150
      was detected in most muscle samples from healthy individuals aged 16-71 years,
      but was not present in any mouse muscle samples up to the age of 18 months. Real
      time qPCR of human muscle samples showed that there was an age-related increase
      in both the full length lamin A and LMNA Delta150 transcripts, whereas their
      protein levels did not change significantly with age. These findings indicate
      that there is a basal level of mis-splicing during LMNA expression that does not
      change with ageing in human muscle, but at levels that do not result in increased
      aberrant protein. The significance of these findings in the pathophysiology of
      muscle ageing is uncertain and warrants further investigation. 

PMID- 24294365
TI  - The correlation between morphology and the expression of TGF-beta signaling
      pathway proteins and epithelial-mesenchymal transition-related proteins in
      synovial sarcomas.
AB  - Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late
      local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT)
      has been implicated in the pathogenesis of diverse human malignancies.
      Immunohistochemical techniques were used to assess EMT-related proteins (E
      cadherin, N-cadherin, beta-catenin, Snail, and Slug) and the TGF-beta1 pathway
      (TGF-beta1 and Smad2/3) proteins expression in different histological subtypes
      and epithelial mesenchymal compositions of SS. The expression of cell-surface (E
      cadherin) and cytoskeletal proteins (beta-catenin) were higher significantly in
      biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic
      fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively
      correlated with expression Snail, Slug, TGF-beta1, and Smad2/3. The expression
      levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV;
      P=0.047, P=0.021) and TGF-beta1 exhibited a tendency toward a positive
      correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate
      with the histological grade (p>0.05). Interestingly, our data showed that
      expression of E-cadherin protein correlated with greater survival in SS patients.
      Overexpression of Snail, and TGF-beta1 is associated with suppressed expression
      of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may
      have developed via neoplastic EMT. 

PMID- 24294366
TI  - EGFR mutation testing on cytological and histological samples in non-small cell
      lung cancer: a Polish, single institution study and systematic review of European
      incidence.
AB  - The targeted treatment of advanced non-small-cell lung cancer (NSCLC) depends on
      confirmation of activating somatic EGFR mutation. The aim of the study was to
      evaluate the incidence of EGFR mutations in NSCLC detected in cytological and
      histological material and present literature review on European EGFR mutation
      incidence. 273 patients with confirmed NSCLC were entered into the study: 189
      histological, paraffin-embedded materials, 12 fresh and 72 fixed cytological
      specimens. DNA was extracted from both types of material and the EGFR mutation in
      exons 18-21 was analyzed by direct sequencing. In addition the EGFR gene copy
      number in cases with sufficient histological material (110 patients) was
      evaluated by fluorescent in situ hybridization (FISH) technique. The percentage
      of EGFR somatic mutations was 10.62%. FISH positive results (amplification or
      high polysomy of EGFR gene) were identified in 33 patients (30.0%). The strongest
      clinicopathological correlation with the EGFR mutation was found for histological
      type (adenocarcinoma; p < 0.01), gender (females; p < 0.01) and FISH positive
      result (p < 0.05). This is the first, single institution study that estimates the
      EGFR mutation incidence in the Polish population. Cytological material recovered
      from fixed preparations and stained with hematoxylin and eosin showed DNA quality
      comparable to fresh tumor cells and histological samples. 

PMID- 24294367
TI  - TLR2-deficiency of cKit+ bone marrow cells is associated with augmented potency
      to stimulate angiogenic processes.
AB  - OBJECTIVE: Toll-like receptor 2 (TLR2)-deficiency is associated with the
      preservation of vascular function and TLR2-deficient (TLR2(-/-)) mice exhibit
      increased neovascularization following induction of hindlimb ischemia.
      Hematopoietic stem cells play an important role in ischemia-induced angiogenesis
      and we now investigated whether the effects observed in TLR2(-/-) mice may be
      attributed to TLR2 deficiency on bone marrow-derived stem cells. APPROACH AND
      RESULTS: cKit-positive (cKit(+)) bone marrow cells (BMC) were isolated from wild
      type (WT) and TLR2(-/-) mice employing MACS-bead technology. Co-incubation of
      TLR2(-/-)cKit(+) BMC with mature endothelial cells (ECs) resulted in increased
      tube formation of ECs on matrigel, augmented sprouting in a 3D-collagen matrix
      and increased migratory capacity compared to co-incubation with WT cKit(+) BMC.
      In an in vivo matrigel plug assay, TLR2(-/-)cKit(+) BMC exhibited enhanced
      formation of capillary-like networks. In a murine model of hindlimb ischemia,
      administration of TLR2(-/-) cKit(+) BMC to WT mice augmented capillary density
      and reperfusion of ischemic M. gastrocnemius muscle tissue to the level of TLR2(
      /-) mice. Western Blot analysis revealed comparable expression of CXCR4 on TLR2(
      /-)cKit(+) BMC but increased activation of the PI3K downstream signaling molecule
      protein kinase B (PKB/AKT) compared to WT cKit(+) cells. CONCLUSIONS: The absence
      of TLR2 on cKit(+) BMC is associated with augmented potency to support angiogenic
      processes in vitro and in vivo. Functional inhibition of TLR2 may therefore
      provide a novel tool to enhance stem cell function for the treatment of vascular
      diseases.

PMID- 24294368
TI  - MiR-195 inhibits proliferation and growth and induces apoptosis of endometrial
      stromal cells by targeting FKN.
AB  - MiR-195, which exhibits a proliferation-inhibiting role in different tumors, has
      been reported to be down-regulated in the ectopic endometrium. The aim of this
      study was to determine the impact of miR-195 on the biological characteristic of
      the endometrial stromal cells (ESCs). MiR-195 has been presumed to target the 3'
      untranslated regions (3'-UTR) of Fractalkine (FKN), which also plays important
      roles in endometriosis. Fluorescence reporter assays showed that miR-195
      effectively binds to the 3'-UTR of FKN. The normal ESCs showed a significant
      higher miR-195 expression than that of eutopic and ectopic ESCs associated with
      endometriosis, while the FKN expression showed opposite results. MiR-195 mimics
      inhibited proliferation and growth and induced apoptosis of eutopic ESCs, and
      these effects were abolished by FKN-siRNA. miR-195 could decrease the expression
      of survivin, matrix metalloproteinase-9 (MMP9) and up-regulate the expression of
      CD82, tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 of eutopic ESCs
      by targeting FKN. Our study has demonstrated for the first time that miR-195
      plays important roles in regulating the functions of ESCs through targeting FKN.
      The information may be useful for developing a new therapeutic strategy for
      endometriosis. 

PMID- 24294369
TI  - Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal
      cancer: its relationship to clinicopathological parameters.
AB  - Cancer testis (CT) antigens are attractive targets for cancer immunotherapy
      because their expression is restricted in normal germ line tissues but frequently
      detected in variety of tumors. OY-TES-1 is identified as a member of CT antigens.
      Current knowledge about OY-TES-1 expression in colorectal cancer (CRC) is solely
      based on mRNA analysis. None of previous researches has studied OY-TES-1 at
      protein level. In this study, OY-TES-1 polyclonal antibody was generated. The
      expression of OY-TES-1 mRNA and protein was detected by RT-PCR and
      immunohistochemistry in 60 CRC and paired adjacent non-tumor tissues, 24
      colorectal adenoma and 3 normal colon tissues, respectively. Sera from 73 CRC
      patients were also tested for OY-TES-1 antibody by ELISA. Our results showed that
      the frequency of OY-TES-1 mRNA expression was statistically higher in CRC (73.3%,
      44/60) than that in adjacent non-tumor tissue (55.0%, 33/60) and colorectal
      adenoma (45.8%, 11/24). For the first time, OY-TES-1 protein expression was found
      in (43.3%, 26/60) of CRC tissues, but absent in any of adjacent non-tumor and
      colorectal adenoma tissues. No OY-TES-1 expression was found in normal colon by
      either RT-PCR or immunohistochemistry. Furthermore, OY-TES-1 protein expression
      was correlated with tumor invasion stage (P=0.004) and histological grade
      (P=0.040). Anti-OY-TES-1 antibody was detected in (9.6%, 7/73) of CRC patients'
      sera but not in 76 healthy donors. This finding demonstrates that OY-TES-1 is
      frequently expressed in CRC and is able to induce humoral immune response
      spontaneously in CRC patients, suggesting that it might be a promising
      immunotherapy target for CRC. 

PMID- 24294370
TI  - Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in
      patients with small cell lung cancer.
AB  - OBJECTIVES: The central issue in this study is to investigate the expression of
      Sex determining region Y-BOX2 (SOX2) and fibroblast growth factor receptor 1
      (FGFR1), evaluate their clinicopathological variables and prognostic significance
      in small cell lung cancer (SCLC). METHODS: Specimens from 222 SCLC patients and
      53 adjacent normal lung tissues were detected by the immunohistochemistry for
      SOX2 and FGFR1 expression. The relationship between the expression of both
      markers and survival status was determined. RESULTS: Overexpression of SOX2 and
      FGFR1 were revealed in SCLC tumors than in normal tissues (P<0.05). SOX2
      expression was associated with clinical stage (P=0.014) and lymph node status
      (P=0.041). Besides, FGFR1 expression was significantly higher in ever smokers
      (P=0.030) and late stage SCLC (P=0.005). SOX2, FGFR1 and TNM stage were
      independent prognostic factors for overall survival (OS) and Recurrence-free
      survival (RFS) by multivariate analysis. In stage I patients, only overexpression
      of SOX2, but not of FGFR1, predicted poor OS (0.027) and RFS (P=0.013). According
      to the expression of SOX2 and FGFR1, patients were categorized into three groups.
      Patients with elevated expression of both markers belonged to the group with the
      shortest RFS (P<0.0001) and OS (P<0.0001). CONCLUSIONS: Increased expression of
      SOX2 and FGFR1 may be available as poor prognostic indicators in SCLC patients.

PMID- 24294371
TI  - Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of
      the skin.
AB  - Claudins are tight junction proteins regulating the paracellular permeability of
      cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a
      sample set consisting of a total of 93 cases representing normal skin, actinic
      keratoses and squamous cell carcinomas of the skin. There were several changes
      found in claudin expression. Claudin 1 appeared to be progressively decreased in
      solar keratosis and skin squamous cell carcinomas compared to normal skin while
      expression of claudin 2 was increased. With claudins 3 and 5 occasional
      immunoreactivity was found in squamous cell carcinomas. Claudins 4 and 7 were
      variably expressed in skin neoplasia compared to normal skin. According to the
      results expression of claudins 1 and 2 change in parallel with the severity of
      the epidermal preneoplastic and neoplastic lesions thus probably influencing the
      disturbed epithelial polarity characteristic of these lesions. Claudin 1 under-
      and claudin 2 overexpression also lead to a leakier epithelial barrier function
      of the skin with a resulting damage to skin epithelial resistance. Other claudins
      investigated in this study did not show progressive changes even though
      occasional overexpression of them was found in skin squamous cell carcinoma. 

PMID- 24294372
TI  - KAT5 and KAT6B are in positive regulation on cell proliferation of prostate
      cancer through PI3K-AKT signaling.
AB  - Histone modifications play important roles in the tumorigenesis and progression
      of prostate cancer (PCa) and genes involved in histone modifications are seemed
      as ideal targets for treatment of PCa patients. However, clinical trials have
      shown that those existing drugs exert the minimal antitumor activity and excess
      adverse effects on PCa patients. Therefore, it is of great interest to figure out
      novel specific biomarkers to guide the development of new drugs. In present
      study, an RNAi screening with 44 genes involved in histone modifications was
      applied to a PCa cell line, Du145. The results showed that nine genes were in
      positive regulation of Du145 cell growth. Then four selected genes (KAT2B, KAT5,
      KAT6B and HDAC1) were found to exert this effect by a gene-specific manner when
      silenced. And then KAT5 or KAT6B silenced cells were subjected to DNA microarray
      analysis. The common differentially expressed genes were analyzed by Ingenuity
      Pathway Analysis (IPA) and found that PDEF signaling, EIF2 signaling and PI3K
      signaling was suppressed following by KAT5 or KAT6B silencing. Subsequent
      immunoblotting assay showed that AKT signaling was inhibited, which suggested
      that KAT5 or KAT6B regulates cancer cell growth through PI3K-AKT signaling.
      Together with our published data [31] that AURKA inhibitoin increased drug
      sensitivity of DU145, our work demonstrated the underlying mechanism that how the
      acetylation enzyme regulates cancer cells survial and might provide potential
      therapeutic targets for prostate cancer patients in future epigenetic drug
      development. 

PMID- 24294373
TI  - Mouse p63 variants and chondrogenesis.
AB  - As a critical member of the p53 family of transcription factors, p63 has been
      implicated a role in development than in tumor formation, because p63 is seldom
      mutated in human cancers, while p63 null mice exhibit severe developmental
      abnormalities without increasing cancer susceptibility. Notably, besides the
      major epithelial and cardiac defect, p63 deficient mice show severe limb and
      craniofacial abnormalities. In addition, humans with p63 mutations also show
      severe limb and digit defects, suggesting a putative role of p63 in skeletal
      development. There are eight p63 variants which encode for the TAp63 and
      DeltaNp63 isoforms by alternative promoters. How these isoforms function during
      skeletal development is currently largely unknown. Our recent transgenic studies
      suggest a role of TAP63alpha, but not DeltaNP63alpha, during embryonic long bone
      development. However, the moderate skeletal phenotypes in the TAP63alpha
      transgenic mice suggest requirement of additional p63 isoform(s) for the limb
      defects in p63 null mice. Here, we report analysis of mouse p63 variants in MCT
      and ATDC5 cells, two cell models undergo hypertrophic differentiation and mimic
      the process of endochondral bone formation upon growth arrest or induction. We
      detected increased level of p63 variants in hypertrophic MCT cells by regular RT
      PCR analysis. Further analysis by qRT-PCR, we detected significantly upregulated
      level of gamma variant (p<0.05), but not alpha or beta variant (p>0.05), in
      hypertrophic MCT cells than in proliferative MCT cells. Moreover, we detected
      upregulated TAP63gamma in ATDC5 cells undergoing hypertrophic differentiation.
      Our results suggest that TAp63gamma plays a positive role during endochondral
      bone formation. 

PMID- 24294374
TI  - Delineation of biological and molecular mechanisms underlying the diverse
      anticancer activities of mycophenolic acid.
AB  - BACKGROUND: Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA)
      which has been widely used for the prevention of acute graft rejection, is a
      potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) that is up
      regulated in many tumors and potentially a target for cancer therapy. MPA is
      known to inhibit cancer cell proliferation and induces apoptosis; however, the
      underlying molecular mechanisms remain elusive. METHODS: We first demonstrated
      MPA's antiproliferative and proapoptotic activities using in vitro studies of 13
      cancer cell lines and a xenograft model. Key proteins involved in cell cycle,
      proliferation and apoptosis were analyzed by Western blotting. RESULTS: In vitro
      treatment of thirteen cancer cell lines indicated that five cell lines (AGS, NCI
      N87, HCT-8, A2780 and BxPC-3) are highly sensitive to MPA (IC50 < 0.5 MUg/ml),
      four cell lines (Hs746T, PANC-1, HepG2 and MCF-7) are very resistant to MPA (IC50
      > 20 MUg/ml) and the four other cell lines (KATO III, SNU-1, K562 and HeLa) have
      intermediate sensitivity. The anticancer activity of MPA was confirmed in vivo
      using xenograft model with gastric AGS cell line. Further in vitro analyses using
      AGS cells indicated that MPA can potently induce cell cycle arrest and apoptosis
      as well as inhibition of cell proliferation. Targeted proteomic analyses indicate
      that many critical changes responsible for MPA's activities occur at the protein
      expression and phosphorylation levels. MPA-induced cell cycle arrest is achieved
      through reduction of many cell cycle regulators such as CDK4, BUB1, BOP1, Aurora
      A and FOXM1. We also demonstrate that MPA can inhibit the PI3K/AKT/mTOR pathway
      and can induce caspase-dependent apoptosis. CONCLUSIONS: These results suggest
      that MPA has beneficial activities for anticancer therapy through diverse
      molecular pathways and biological processes.

PMID- 24294375
TI  - Increased ZO-1 expression predicts valuable prognosis in non-small cell lung
      cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the expression of Zonula
      Occludens-1 (ZO-1) and its potential value as prognostic indicator of survival in
      patients with primary non-small cell lung cancer (NSCLC). METHODS: Quantitative
      real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry with
      tissue microarrays were used to characterize the expression of the ZO-1 mRNA and
      protein in NSCLC. The correlation of ZO-1 expression with clinical
      characteristics and prognosis was determined by statistical analysis. RESULTS:
      The ZO-1 mRNA and protein levels were significantly lower in NSCLC tissue
      compared with corresponding peritumoral tissue (P<0.05). ZO-1 protein expression
      in NSCLC was related to age (P=0.042) and 5-year survival (P<0.001). Kaplan-Meier
      survival and Cox regression analyses revealed that low ZO-1 expression (P<0.001)
      and later stage grouping by TNM (P=0.031) were independent factors predicting
      poor prognosis for patients with NSCLC. CONCLUSIONS: Our findings provide the
      first evidence that high expression of ZO-1 is associated with good prognosis in
      NSCLC.

PMID- 24294376
TI  - Bee venom ameliorates compound 48/80-induced atopic dermatitis-related symptoms.
AB  - Honeybee (Apis mellifera L.) venom (BV) has been traditionally used for the
      treatment of pain and inflammatory diseases such as itchy skin problems. However,
      the precise mechanism of BV in ameliorating the scratching behavior is not fully
      understood. OBJECTIVE: In order to evaluate the effect of BV on atopic dermatitis
      related symptoms in mice, we used a mouse skin scratching model induced by
      compound 48/80. The anti-itch effect of BV was investigated in a compound 48/80
      induced mouse scratching behavior model. BALB/c mice were injected
      intraperitoneally with vehicle (saline 0.9%) or BV (0.01 and 0.1 mg/kg). One hour
      after treatment, the animals received a subcutaneous injection of compound 48/80.
      Intraperitoneal administration of BV (0.01 and 0.1 mg/kg) attenuated compound
      48/80-induced scratching behaviors. The anti-scratching behavior effect of BV was
      in proportional to its vascular permeability effects. Treatment with BV also
      inhibited the degranulation of mast cells and the production of pro-inflammatory
      cytokines in compound 48/80-treated skin tissues. According to these results, BV
      may improve atopic dermatitis-related symptoms by inhibiting the mast cell
      degranulation and pro-inflammatory cytokine expression.

PMID- 24294377
TI  - Decreased expression of miR-218 is associated with poor prognosis in patients
      with colorectal cancer.
AB  - The identification of biomarkers in colorectal cancer (CRC) diagnosis and therapy
      is important in achieving early cancer diagnosis and improving patient outcomes.
      The aim of this study was to examine clinical significance of miR-218 expression
      in sera and tissues from CRC patients. A total of 189 cases and 30 healthy
      subjects were included. The expression levels of miR-218, SLIT2 and SLIT3 were
      measured by quantitative reverse transcription PCR (qRT-PCR). The relationship
      between miR-218 expression and clinicopathological characteristics was
      investigated. The expression levels of miR-218, SLIT2 and SLIT3 in CRC tissues
      were decreased than those in adjacent normal tissues (all P < 0.05). miR-218
      expression was significantly associated with TNM stage, lymph node metastasis
      (LNM) and differentiation (all P < 0.05). Patients with low miR-218 expression
      had shorter survival time than those with high miR-218 expression (P = 0.036).
      Furthermore, the expression levels of serum miR-218 in CRC patients were lower
      than those in controls (P = 0.005). An increased level of serum miR-218 was found
      1 month after surgery (P = 0.026). In conclusion, the miR-218 may has important
      roles in the development and progression of CRC and be a potential diagnostic and
      prognostic biomarker of CRC. 

PMID- 24294378
TI  - HIF-1alpha and VEGF expression correlates with thrombus remodeling in cases of
      intravascular papillary endothelial hyperplasia.
AB  - Intravascular papillary endothelial hyperplasia (IPEH) is histopathologically
      characterized by endothelium-lined papillary structures encircling an acellular
      fibrin core. The process of IPEH pathogenesis is unclear. The purpose of our
      study was to identify histopathological and immunohistochemical characteristics
      of IPEH to better understand the pathogenesis of this disease. After reviewing
      microscopic and medical records from Kyungpook National University Hospital, we
      selected 16 cases of IPEH. Masson's trichrome and immunohistochemical staining as
      well as hematoxylin-eosin staining for 16 cases of IPH were performed.
      Immunohistochemical studies included CD31, CD68, mast cell tryptase, hypoxia
      inducible factor-1 (HIF-1alpha), and vascular endothelial growth factor (VEGF).
      Sections from all our cases showed three distinct histological regions including
      a papillary portion with hyalinized fibrous or fibroblastic cores, an area
      containing an unorganized thrombus, and organization area with an ingrowth of
      endothelial cells, myofibroblasts, and fibroblasts. In the organization area, HIF
      1alpha-positive cells were identified in the loose connective tissue. Endothelial
      cells forming vascular channels were negative for HIF-1alpha while VEGF was
      highly expressed in both interstitial mononuclear and endothelial cells. In the
      papillary portion, the cellular cores were strongly positive for both HIF-1alpha
      and VEGF, but the acellular cores were negative. Our investigation confirmed that
      IPEH is a reactive lesion that incidentally arises during the organization
      process of older thrombi. It was also found that HIF-1alpha and VEGF expression
      was dependent on the thrombus remodeling stage in cases of IPEH. 

PMID- 24294379
TI  - Immunohistochemical expression of nuclear and cytoplasmic survivin in
      gastrointestinal carcinoma.
AB  - Survivin is a protein that is highly expressed in many embryonic tissues, as well
      as most human tumors. Prior studies have reported both positive and negative
      correlations between survivin expression and cancer prognosis, but these
      associations remain controversial. In the present study, we assessed the
      expression of nuclear and cytoplasmic survivin in gastrointestinal carcinomas.
      Using these data, we determined the correlation between nuclear and cytoplasmic
      survivin and, further, investigated correlations between survivin expression and
      clinicopathological parameters. Seventy-two advanced gastric adenocarcinomas and
      78 colorectal adenocarcinomas were analyzed for survivin expression by
      immunohistochemistry. Expression of both nuclear and cytoplasmic survivin was
      significantly higher in colorectal carcinomas than in gastric carcinomas (P <
      0.01). There was a positive correlation between nuclear and cytoplasmic
      expression of survivin (r = 0.42, P < 0.001). In gastric carcinomas, the level of
      survivin protein expression was associated with tumor differentiation, patient
      age, and lymphatic invasion (P < 0.05, 0.01, and 0.01, respectively). In
      colorectal carcinomas, the level of nuclear survivin expression was significantly
      higher in females than in males (P < 0.05). There were no significant
      associations between survivin expression and most of the clinicopathological
      parameters. Nevertheless, there was a trend towards an inverse correlation
      between nuclear survivin expression and tumor aggressiveness in gastric
      carcinoma; there was a similar trend for cytoplasmic survivin expression. In
      summary, our results suggest that levels of nuclear and cytoplasmic survivin
      expression differ between gastric carcinoma and colorectal carcinoma. 

PMID- 24294380
TI  - Clinical usefulness of immunohistochemistry for plakoglobin, N-cadherin, and
      connexin-43 in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.
AB  - Diagnosing arrhythmogenic right ventricular cardiomyopathy (ARVC) is often
      challenging because no single diagnostic tool is available to detect the disease.
      We evaluated whether analysis of plakoglobin, N-cadherin, and connexin-43
      immunoreactivity can be used as a significant test in diagnosis of ARVC. We
      selected subjects with suspicion of ARVC (n=22) in patients who underwent
      endomyocardial biopsy (EMB) in Kyungpook National University Hospital (n=1326).
      The patients (n=22) were classified into definite ARVC patients (n=17) and
      borderline ARVC (n=5). We selected control subjects (n=20) who were autopsied and
      died of non-cardiac disease. Hematoxylin-eosin, Masson's trichrome, and
      immunohistochemical stains for plakoglobin, N-cadherin, and connexin-43 were used
      for all specimens. Reduced immunoreactivity of plakoglobin was observed in 13
      (76%) of the 17 patients with a definite ARVC and in 4 (80%) of the 5 patients
      with a borderline ARVC. All subjects displayed no significant reduction of the
      immunoreactivity for connexin-43 as well as for N-cadherin. Our investigation
      revealed that the immunohistochemical analysis for plakoglobin had an accuracy of
      81%, 76% sensitivity, and 84% specificity in diagnosis of ARVC. Results of our
      study showed that the immunohistochemical analysis of plakoglobin had a
      relatively high sensitivity and specificity in ARVC, but immunohistochemistry for
      plakoglobin alone could not be relied upon as a diagnostic test for ARVC. We
      confirmed that N-cadherin and connexin-43 had no diagnostic value in ARVC. 

PMID- 24294381
TI  - Clear cell papillary renal cell carcinoma: a clinicopathological study
      emphasizing ultrastructural features and cytogenetic heterogeneity.
AB  - Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal
      neoplasm, which was initially described in end-stage renal disease (ESRD), but
      some cases have been reported in otherwise normal kidneys. We report a series of
      11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was
      available for 8 patients. No patients developed local recurrence, distant or
      lymph-node metastasis, or cancer death. Histologically, all tumors exhibit
      morphologic features typical of CCPRCC including a mixture of cystic and
      papillary components, covered by small to medium-sized cuboidal cells with
      abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity
      for CK7, CA9, Vim, and HIF-1alpha, coupled with negative reactions for CD10,
      P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of
      chromosomes 3 (monoploid chromosome 3) was detected in 3 cases.
      Ultrastructurally, the tumor cells composed of numerous glycogens with scanty
      cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In
      conclusion, the coexpression of CA9 and HIF-1alpha in the absence of VHL gene
      abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms
      independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome
      3) was detected in 3 cases suggesting that at least some of these lesions have
      demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed
      of numerous glycogens with scanty cell organelles, reminiscent of CCRCC
      suggesting the close pathogenesis relationship of CCPRCC with CCRCC. 

PMID- 24294382
TI  - Transposable hypomethylation is associated with metastatic capacity of primary
      melanomas.
AB  - Despite the strong progress has been made in the field of melanoma epigenetics,
      the importance of genome-wide demethylation or hypomethylation remains
      underestimated. However, this phenomenon might also reflect important epigenetic
      alterations due to its ability to cause genetic instability. Furthermore, no
      methylation-based distinction has been drawn among the diverse primary melanoma
      subtypes. To assess global methylation we measured the methylation level on the 6
      CpG sites of LINE1 sequences in 46 primary melanomas in association with
      patients' survivals and the clinicopathological characteristics of specimens. We
      demonstrate that LINE1 hypomethylation is accompanied by the shortened relapse
      free survival of melanoma patients; however, Cox regression analysis shows a
      direct relationship between the overall loss of 5-methylcytosine and metastatic
      potential of primary melanomas, which is confirmed by Kruskal-Wallis tests with
      Dunn's Multiple Comparison Post-test showing that not only the presence but the
      number of metastases during the 5-year follow-up period is associated with the
      transposon demethylation. In this study, we demonstrate the strong influence of
      global DNA demethylation in the metastatic formation of primary melanomas during
      the follow-up period. 

PMID- 24294383
TI  - Leiomyomatosis peritonealis disseminata coexisting with endometriosis within the
      same lesions: a case report with review of the literature.
AB  - Leiomyomatosis peritonealis disseminata (LPD) is an extremely rare condition,
      which is characterized by the presence of multiple peritoneal and subperitoneal
      nodules composed of bland smooth muscle cells. Albeit extremely rare, coexistence
      of endometriosis within LPD lesions has also reported. Herein, we report the
      seventh documented case of LPD coexisting with endometriosis within the same
      lesions and review the pathogenesis of this lesion. A 42-year-old Japanese female
      presented with an abdominal tumor. Computed tomography revealed a tumorous lesion
      in the right ovary and multiple small nodules in the abdominal cavity. Under a
      clinical diagnosis of ovarian cancer with peritoneal dissemination, resection of
      these lesions was performed. Histopathological study of the disseminated
      peritoneal nodules revealed proliferation of interlacing bundles of spindle cells
      with eosinophilic cytoplasm and bland cigar-shaped nuclei. Mitotic figures were
      hardly seen. The peritoneal nodules of the rectum had cystic cavities within the
      spindle cell bundles, and endometrial glands and stroma were present around the
      cystic cavities and spindle cells. The resected tissues of the ovary and cecum
      showed the same histopathological features. Accordingly, a diagnosis of LPD with
      endometriosis within the same lesions was made. A possible origin of LPD is
      thought to be the submesothelial multipotential stem cells, also referred to as
      the secondary mullerian system. The presence of endometrial tissues within LPD
      lesions, as seen in the present case, also support this hypothesis because
      endometrial tissues are also derived from the mullerian system. 

PMID- 24294384
TI  - Role of calretinin immunohistochemical stain in evaluation of Hirschsprung
      disease: an institutional experience.
AB  - BACKGROUND: The use of calretinin immunostain (IHC) in the evaluation of rectal
      suction biopsies for Hirschsprung disease (HD) has been reported by Kapur et al.
      and others. The first goal of this article is to report our institutional
      experience with the use of calretinin in specimens for evaluation of HD. The
      second goal is to describe the pattern of expression of calretinin in the
      junction of ganglionic-to-aganglionic segment of pull through specimens of
      patients with a previous diagnosis of HD on suction rectal biopsy. MATERIAL AND
      METHODS: Three pathologists at University of Texas at Houston evaluated 28 rectal
      biopsy specimens from 2010-2011. The patients' age ranged from 15 days to 8
      years. Twenty-three cases were suction biopsies, and five were rectal full
      thickness biopsies. Hematoxylin-eosin (H&E) stain was performed on at least 80
      levels for the suction biopsy specimens. Calretinin immunohistochemical stain was
      performed on levels 40-42 in all cases, with adequate controls. The H&E slides of
      nine pull through specimens with a diagnosis of HD on a suction rectal biopsy
      that was evaluated in this study, were evaluated. Calretinin IHC was performed on
      the slide(s) showing the junction of aganglionic-to-normal rectum, along with
      adequate controls. RESULTS: The presence of ganglion cells consistently
      correlated with calretinin-positive thin nerve fibrils in the lamina propria,
      muscularis mucosae and superficial submucosa. These nerve fibrils were absent in
      the aganglionic segments of bowel and in the areas without ganglion cells from
      the junction of normal with diseased rectum. Calretinin was strongly expressed in
      the submucosal and subserosal nerve trunks in the ganglionic segment. It had
      faint expression in the thick nerve trunks from the areas without ganglion cells
      1.6-2.5 cm proximal to the normal rectum. No calretinin expression was seen in
      the nerve trunks in the rest of the aganglionic segment. CONCLUSION: The pattern
      of expression of calretinin in rectal suction biopsies in HD and normal rectum
      coincide with the ones previously described in the literature. Calretinin IHC
      offered additional diagnostic value in the specimens with inadequate amount of
      submucosa and rarely seen ganglion cells. The pattern of expression of calretinin
      in HD pull-through specimens correlates with the rectal biopsy ones. Faint
      positivity of the thick submucosal and subserosal nerves in the absence of
      ganglion cells and calretinin positive nerve fibrils, is characteristic of the
      junction of the aganglionic-to-normal rectum. We are the first ones to document
      this finding.

PMID- 24294385
TI  - Clinical usefulness of fine needle aspiration cytology in patients less than 20
      years old: a 10-year experience at a single institution.
AB  - The purpose of this study was to identify the spectrum of cytological diagnoses
      and evaluate the diagnostic effectiveness of fine needle aspiration cytology
      (FNA) in patients less than 20 years old. The subjects were selected by
      retrospectively reviewing records from 1999 to 2009. Selected patients less than
      20 years old underwent FNA. Cytological and histological slides of samples from
      the subjects were reviewed. Our study included a total of 909 subjects with a
      mean age of 14.6 years. The majority of the FNA samples were taken from lymph
      nodes (n = 448, 49.3%), with the remaining aspirates obtained from the thyroid
      gland (n = 247, 27.2%), soft tissues of head and neck masses (n = 106, 11.7%),
      salivary glands (n = 75, 8.3%), breasts (n = 18, 1.9%), skins (n = 9, 1.0%) and
      soft tissues of extremity (n = 6, 0.7%). The majority (87.6%, n = 796) of the FNA
      samples were categorized as 'benign', with the remaining designated as 'atypical
      lesion' (n = 18, 2.0%), 'malignant' (n = 24, 2.6%), or 'inadequate specimen' (n =
      71, 7.8%). FNA accuracy was 92% for diagnosing cancer. Specificity and
      sensitivity were 99% and 63%, respectively. Our study first revealed that FNA has
      a high specificity for diagnosing cancer in various anatomical locations in young
      patients and can be confidently used as an effective tool for diagnosing
      malignancies in young individuals with a clinically suspicious lesion. 

PMID- 24294386
TI  - Association between PKA gene polymorphism and NTDs in high risk Chinese
      population in Shanxi.
AB  - OBJECTIVE: This study aimed to investigate the single nucleotide polymorphisms
      (SNPs) of PKA and neural tube defects (NTDs) in Chinese population. METHOD: A
      total of 183 NTDs cases and 200 healthy controls were used in this study. 7
      selected single nucleotide polymorphism (SNP) sites in the PKA gene were analyzed
      with MassArray high-throughput DNA analyzer with matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. A series of
      statistical methods were carried out to investigate the correlation between the
      SNPs and the patient susceptibility to NTDs. RESULTS: Statistical analysis showed
      a significant correlation between the SNP sites rs12132032 in PRKACB and NTDs.
      The AA genotype, A-allele and dominant AA in rs12132032 significantly increased
      the incidence of NTDs especially anencephaly (OR=3.87, 95% CI: 1.80-8.34 with
      genotype; OR=2.08, 95% CI: 1.43-3.04 with allele; OR=3.10, 95% CI: 1.53-6.26 with
      dominant). The T-allele of rs594631 in PRKACB was correlative with NTDs in male
      but not in female. CONCLUSIONS: The gene polymorphism loci rs12132032 in PRKACB
      maybe a potential risk factor for anencephaly in Chinese population from Shanxi,
      while gender susceptibility may influence the correlation.

PMID- 24294387
TI  - A new technique for the obliterative urethral strictures.
AB  - There have been a troublesome problem to treat with obliterative urethral
      strictures, the challenge is how to reduce wound of surgery and improve
      therapeutic success rates. In this study, we reported single-hospital institution
      case-series including 97 patients with obliterative urethral strictures were
      enrolled with "three lines lie within one imaginary plane (TLLWOIP)" to treat
      with patients with the obliterative urethral strictures. Perioperative variables
      and success rates were evaluated. Urinary flow rate, residual urine (RU) volume
      and quality-of-life score (QoLs) of patients were analyzed. In the obliterative
      urethral strictures, postoperative maximum urinary flow rate was 24.36 +/- 10.69
      ml, and postoperative RU volume and QoLs outcomes were significantly lower than
      preoperative outcomes with TLLWOIP. A total of success rate was 62.9% with
      TLLWOIP. Our results suggested that it was ideal candidates for initial treatment
      with TLLWOIP for the obliterative urethral strictures.

PMID- 24294388
TI  - Diffuse large B-cell lymphoma of the uterus suspected of having transformed from
      a marginal zone B-cell lymphoma harboring trisomy 18: a case report and review of
      the literature.
AB  - The patient was a 72-year-old female with the chief complaint of abdominal
      fullness. A giant primary myoma of the uterine cervix was suspected, and total
      hysterectomy was performed. Based on a postoperative histopathological
      examination of the tumor a diagnosis of diffuse large B-cell lymphoma (DLBCL) was
      made in the uterus and a mass in the greater omentum was diagnosed as a marginal
      zone B-cell lymphoma (MZBCL). No flow-cytometry studies or chromosome or gene
      examinations were performed on a fresh specimen. The results of an examination of
      a paraffin block histopathology specimen by fluorescence in-situ hybridization
      (FISH) showed no mucosa associated lymphoid tissue lymphoma translocation gene 1
      (MALT1) (18q21.1), B-cell lymphoma 2 (BCL2) (18q21.3), or BCL6 (3q27) split
      signals in either the uterus or the greater omentum, however, trisomy 18 was
      detected in approximately 50%-70% of the tumor cells in both the uterus and the
      greater omentum. Trisomy 18 was present in around 15-33% of the DLBCL cells and
      MZBCL cells. These findings suggested a strong possibility that the tumor cells
      in the uterus and greater omentum were the same clone and that transformation
      from MZBCL to DLBCL had occurred. Since DLBCLs that result from a transformation
      usually have a worse outcome than de novo DLBCLs, even when a DLBCL seems to have
      originated in the uterus the surrounding tissue should always be examined, and
      caution should be exercised in regard to transformation from a low-grade B-cell
      lymphoma to a DLBCL. 

PMID- 24294389
TI  - Long segmental hyperplasia of interstitial cells of Cajal with giant diverticulum
      formation.
AB  - Sporadic gastrointestinal stromal tumors (GISTs) usually form a well
      circumscribed mass. In contrast, diffuse interstitial cell of Cajal (ICC)
      hyperplasia along the Auerbach plexus without a discrete mass may occur in
      patients with germline mutations in the NF1, c-KIT or PDGFRA genes. However,
      sporadic, diffuse ICC hyperplasia without c-KIT or PDGFRA mutations has not been
      reported. We describe herein one such case, forming a giant diverticulum. A 63
      year-old woman with no features of Neurofibromatosis 1 (NF1) presented with
      increasing abdominal pain for more than 30 years. A large, diverticulum-like mass
      in the ileum was resected. Microscopically, a diffuse proliferation of bland
      spindle cells was seen extending for 12 cm, replacing the muscularis propria and
      lined by intact mucosa. The spindle cells were CD117+/CD34+/DOG1+/SMA+/Desmin
      /S100-. Mutation analyses did not reveal any mutations in c-KIT or PDGFRA. The
      lesion had two silent mutations in the NF1 gene. It is rare of the diffuse form
      of sporadic ICC hyperplasia showing diffuse longitudinal microscopic growth
      completely replacing the muscularis propria, mimicking diffuse ICC hyperplasia in
      hereditary GIST syndromes, but without solid components and no c-KIT or PDGFRA
      gene mutations. This peculiar form of sporadic ICC hyperplasia may be related to
      intestinal dysmotility in this ileal segment and giant diverticulum formation. 

PMID- 24294390
TI  - Endometrial stromal sarcoma arising in vagina.
AB  - Endometrial stromal sarcoma (ESS) arising in the vagina is an extremely rare
      extrauterine endometrial stroma sarcoma, with only 4 cases reported in the
      literature up to date. Here we report a case of neoplasm originating from vagina.
      A 32-year-old woman complained of intermittent vaginal bleeding especially after
      intercourse. A mass with a diameter of 1.0 cm was found in the middle and upper
      segments of the right posterior vaginal wall. Biopsy showed ESS. Total abdominal
      hysterectomy, unilateral salpingo-oophorectomy (right) and partial vaginectomy
      were performed. No ESS lesion was found in endometrium. The patient received six
      courses of platinum-containing combination chemotherapy after surgery and was
      free of tumor 18 months after the diagnosis of ESS. The diagnosis of ESS relies
      on pathologic examination. CD10 is the most useful immunohistochemical marker for
      the diagnosis of this tumor. The mainstay treatment of ESS is surgery. Local
      excision and ovarian retaining may be considered in premenopausal women. 

PMID- 24294391
TI  - Soft tissue perineurioma and other unusual tumors in a patient with
      neurofibromatosis type 1.
AB  - Perineurioma is a rare benign peripheral nerve sheath tumor featuring perineurial
      differentiation. Perineurioma occurs sporadically with only one reported case in
      the setting of neurofibromatosis type 1 (NF-1). We present a 6.7-cm soft tissue
      perineurioma of the lower leg in a 51-year-old man with proven NF-1. The tumor
      displayed whorled and fascicular pattern with infiltrative margins and expressed
      EMA, GLUT-1, claudin-1, and CD34. Electron microscopy confirmed diagnosis.
      Furthermore, lipomatosis, cutaneous angiomatous nodules, vasculopathy, and iliac
      spine lesion consistent with non-ossifying fibroma were observed. Tumor DNA
      revealed no NF2 mutations or chromosomal aberrations but a germline NF1-deletion
      (c.449_502delTGTT) was detected in his blood sample. His brother displayed
      neurofibromas, duodenal ganglioneuroma and colonic juvenile polyp, and his mother
      a neurofibroma, cutaneous squamous cell carcinoma, and jejunal gastrointestinal
      stromal tumor (GIST); both were affected by NF-1. In conclusion, perineurioma may
      rarely be NF-1 related and should be included in the spectrum of neoplasms
      occurring in this disorder. 

PMID- 24294392
TI  - Post cardiac transplantation T-cell lymphoproliferative disorder presenting as a
      solitary lung nodule.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) is an infrequent, but
      serious complication of solid organ and bone marrow transplantations. The vast
      majority of the cases are of B-cell origin and usually associated with Epstein
      Barr virus (EBV) infection. The non-B (T and NK cell) PTLDs account for up to 14%
      of the PTLD cases in Western countries. We report a case of a 66-year-old man who
      received an orthotopic heart transplant for cardiomyopathy 7 years prior to
      presentation. He was referred to our institution with a hypermetabolic solitary
      right lower lobe lung nodule with an SUV of 9.2 on PET scan. The combined
      histomorphological and immunohistochemical pattern was most consistent with
      monomorphic PTLD, peripheral T-cell lymphoma with angioimmunoblastic features.
      Molecular studies showed clonal T-cell gamma receptor gene rearrangement. Primary
      pulmonary involvement of T-cell PTLD is extremely rare. This is the third
      reported case of T-cell PTLD after cardiac transplantation, primarily involving
      the lung. Further, studies will be required to determine the appropriate
      treatment and prognosis of this rare entity. 

PMID- 24294393
TI  - Adult T-cell leukemia/lymphoma accompanying follicular mucinosis: a case report
      with review of the literature.
AB  - Follicular mucinosis is recognized as one of the histopathological reaction
      patterns characterized by the accumulation of mucin within follicular epithelium.
      It is induced by various causes including inflammatory diseases, and more than
      half of the cases are associated with malignant lymphoma, mainly mycosis
      fungoides. Herein, we describe the third documented case of adult T-cell
      leukemia/lymphoma (ATLL) accompanying follicular mucinosis. A 72-year-old
      Japanese male presented with persistent erythema in his arm and neck. Laboratory
      tests demonstrated positivity for human T-cell leukemia virus (HTLV)-1
      antibodies. Histopathological study of the biopsy specimen from the neck revealed
      superficial perivascular, nodular, and intrafollicular lymphocytic infiltrations.
      These lymphocytes were small- to medium-sized and had convoluted nuclei. Mucoid
      material deposition was observed within the hair follicles, and it was digested
      by hyaluronidase. Immunohistochemically, these lymphocytes were positive for CD3,
      CD4, CD25, and Foxp3. Accordingly, an ultimate diagnosis of ATLL accompanying
      follicular mucinosis was made. The skin is the most common extralymphatic site of
      involvement of ATLL. The present case clearly demonstrated that albeit extremely
      rare, ATLL can cause follicular mucinosis. Therefore, ATLL should be included in
      the differential diagnostic consideration of follicular mucinosis. 

PMID- 24294394
TI  - Follicular hybrid cyst: a combination of bullous pilomatricoma and epidermoid
      cyst.
AB  - The follicular hybrid is composed of more than two components of pilosebaceous
      unit. There are several studies of hybrid cyst, combination of trichilemmal and
      epidermoid cyst was the most frequently reported. In this paper, we reported one
      case of hybrid cyst composed of bullous pilomatricoma and epidermoid cyst. A 14
      year-old girl was complaint of a solitary flesh-colored to erythematous nodule
      with flaccid appearance sized 3.2 * 1.8 cm in diameter on her right upper back
      for one year. The histologic findings showed there were edema and proliferation
      of capillaries in the superficial dermis, a cyst in the middle to deep dermis.
      There were laminated keratins in the cystic space. The cyst wall was composed of
      two different components, one was composed of epithelial cells containing of
      granular layer, and another consisted of basophilic cells, transient cells and
      shadow cells. The cyst not related with Gardner's syndrome. Hybrid cyst such as
      trichilemmal cyst, epidermoid and pilomatricoma cysts maybe have same clinical
      features or mimicking each others, but we can distinguish them from
      histopathology evaluation.

PMID- 24294395
TI  - CD56 positive diffuse large B-cell lymphoma: a case report and literature review.
AB  - CD56 positive B-cell lymphoma is very rare. We experienced a case of CD56
      positive diffuse large B-cell lymphoma, occurred in a young child. A 5-year-old
      girl complained with snoring and open mouth breathing. No any abnormality in
      laboratory or physical examination was present, except enlarged both tonsils.
      Bilateral tonsillectomy was performed. Cut sections of right tonsil showed a 2 cm
      size, solid mass. On microscopically, large monomorphic lymphoid cells were
      diffusely proliferated and showed positivity for CD20 and CD56 and negative for
      Epstein-Barr virus (EBV) polymerase chain reaction (PCR). Monoclonality was
      observed on immunoglobulin heavy chain gene rearrangement. This is a unique case
      with incidentally found and occurred in a young child. 

PMID- 24294396
TI  - Esophageal squamous cell carcinoma in situ overlying leiomyoma: a case report
      with review of the literature.

PMID- 24294397
TI  - Sebaceous carcinoma associated with Bowen's disease: a case report with emphasis
      on the pathogenesis of sebaceous carcinoma.

PMID- 24294398
TI  - Pigmented porocarcinoma: a case report with review of the literature.

PMID- 24294399
TI  - Importance of spondin 1 and cellular retinoic acid binding protein 1 in the
      clinical diagnosis of ovarian cancer.
AB  - BACKGROUND: Diagnosis of ovarian cancer is often delayed because of subtle
      symptoms and a lack of a specific, sensitive test useful for the general
      population. The majority of cases are diagnosed at late stages, after the tumor
      has metastasized and implanted on many other abdominal organs and cavity
      surfaces. A paucity of prognostic markers makes it difficult to define which
      tumors will act aggressively and shorten survival. Hence, it is imperative to
      have new screening tests for diagnosis of ovarian cancer at earlier stages, prior
      to metastatic progression. Diagnosis at these early stages will dramatically
      increase the overall survival of women with ovarian cancer. MATERIAL AND METHODS:
      Based on previously published literature on proposed molecular cell markers in
      ovarian carcinoma, we sought to validate the overexpression of two genes
      (cellular retinoic acid Binding Protein, CRABP-1, and spondin 1) through
      immunohistochemistry. RESULTS: We verified the overexpression of spondin 1 in
      ovarian cancer. Expression of cellular retinoic acid Binding Protein, CRABP-1 in
      whole ovarian cancer tissue sections was higher than in the TMA tissue cores.
      CONCLUSION: Our results thus demonstrate that spondin 1 is a useful marker for
      ovarian cancer; additionally, the high percentages of tumors that are positive
      for spondin 1 make it an ideal target for therapy. CRABP-1 was not expressed at
      high levels in any subtype of ovarian cancer, making it a poor marker.

PMID- 24294400
TI  - Development of a model system to analyze chondrogenic differentiation of
      mesenchymal stem cells.
AB  - High-density cell culture is widely used for the analysis of cartilage
      development of human mesenchymal stem cells (HMSCs) in vitro. Several cell
      culture systems, as micromass, pellet culture and alginate culture, are applied
      by groups in the field to induce chondrogenic differentiation of HMSCs. A draw
      back of all model systems is the high amount of cells necessary for the
      experiments. Further, handling of large experimental approaches is difficult due
      to culturing e.g. in 15 ml tubes. Therefore, we aimed to develop a new model
      system based on "hanging drop" cultures using 10 to 100 fold less cells. Here, we
      demonstrate that differentiation of chondrogenic cells was induced as previously
      shown in other model systems. Real time RT-PCR analysis demonstrated that
      Collagen type II and MIA/CD-RAP were upregulated during culturing whereas for
      induction of hypertrophic markers like Collagen type X and AP-2 epsilon treatment
      with TGF beta was needed. To further test the system, siRNA against Sox9 was used
      and effects on chondrogenic gene expression were evaluated. In summary, the
      hanging drop culture system was determined to be a promising tool for in vitro
      chondrogenic studies. 

PMID- 24294401
TI  - Salivary gland trauma: a review of diagnosis and treatment.
AB  - Salivary gland trauma is uncommon. Parotid gland and duct injuries are far more
      common than injuries to submandibular and sublingual glands due to anatomic
      position. Several methods of treating salivary duct injuries and their
      complications have been advocated. Optimal treatment outcomes can be achieved
      with early diagnosis, adequate evaluation, and proper management. This article
      presents current diagnostic and treatment protocols of salivary gland trauma. The
      anatomy of the salivary glands is briefly described and clinical cases are also
      presented to illustrate the treatment options described. 

PMID- 24294402
TI  - Maxillofacial trauma in central karnataka, India: an outcome of 95 cases in a
      regional trauma care centre.
AB  - Materials and Methods A 6-year retrospective analysis of 111 patients treated for
      maxillofacial fractures in Davangere, Karnataka from January 2004 to December
      2009 was performed. Variables like age, gender, occupation, type of fracture and
      mechanism of injury, concomitant injury, mode of treatment, and complications
      were recorded and assessed. Results Men between 21 and 30 years were mostly
      affected (male-to-female ratio = 10:1; age range = 17.60 years; mean 31.7 +/- 9.8
      [standard deviation]). Most fractures were caused by road traffic accidents
      (RTAs; 74.7%), followed by interpersonal violence (IPV; 15.8%), falls (4.2%),
      industrial hazards and animal attacks (2.1% each), and self-inflicted injury
      (1.1%). Forty-two cases were isolated zygomaticomaxillary complex (ZMC)
      fractures. The total number of facial fractures documented was 316, of which 222
      were purely related to the ZMC; however, 11 were confined only to the midface.
      Fifty-three cases had concomitant lower jaw fractures, totaling 83. Ophthalmic
      injuries occurred in 30.52% of cases. Ninety-two cases were treated with open
      reduction and internal fixation (ORIF), and three cases were managed
      conservatively. The complication rate observed was 25.26%. Conclusion RTA
      continues to be the chief etiological factor in maxillofacial injury with males
      being affected predominantly. IPV and falls next contribute significantly to the
      incidence of such injuries. Concomitant injuries, however, require prompt
      recognition and appropriate management. ORIF still remains the mainstay of
      treatment; however, fixation devices are constantly being improved upon in an
      attempt to reduce immobilization time thereby facilitating early return to
      function with minimal morbidity. Nevertheless, future advances in maxillofacial
      trauma diagnosis and management are likely to reduce associated morbidity. 

PMID- 24294403
TI  - Free flap reconstruction for complex scalp and forehead defects with associated
      full-thickness calvarial bone resections.
AB  - Extensive defects of the scalp and forehead associated with calvarial bone
      resections demand complex reconstructions. Free flaps offer vascularized tissue
      of excellent quality and quantity. We report six patients with extensive scalp
      and forehead defects associated with calvarial bone resections reconstructed with
      free flaps. Five patients also required a cranioplasty. The flaps used were two
      anterolateral thigh flaps, one vastus lateralis flap, one myocutaneous latissimus
      dorsi flap, one latissimus dorsi flap, and one radial forearm flap. All flaps
      survived with no partial necrosis. There were no donor site complications. One
      patient presented an exposure of the alloplastic material used for cranioplasty.
      We strongly recommend the use of free flaps for this kind of reconstruction. 

PMID- 24294404
TI  - Global trends in maxillofacial fractures.
AB  - Background The etiology, demographics, fracture site in facial injury patients
      have been reported worldwide. However, few studies have attempted to identify
      changes in maxillofacial fractures over time periods and between countries. The
      statistics are vastly different due to variations in social, environmental, and
      cultural factors. Methods Data were collected from departmental records between
      1996 and 2006 for patients treated at Christchurch Hospital for facial fractures.
      Variables examined included incidence, demographics, site of fracture, and
      treatment methods. Results A total of 2563 patients presented during the study
      period, 1158 patients in the first half and 1404 patients in the second half.
      Male-to-female ratio was 4:1 in both periods and males in 16- to 30-year group
      accounted for about half of all patients. Interpersonal violence was the most
      common cause of injuries, and there was a decrease in injuries caused by motor
      vehicle accidents. Approximately half of all patients required hospitalization
      and surgery, and the most common method of treatment was open reduction and
      internal fixation. Conclusion Maxillofacial fracture is a common injury in young
      males following interpersonal violence in New Zealand. Studies in other countries
      and over different time periods yield interesting differences in the etiology,
      demographics, and fractures patterns. These are due to environmental, societal,
      cultural, and legislative differences. 

PMID- 24294405
TI  - Radiomorphometric quantitative analysis of vasculature utilizing micro-computed
      tomography and vessel perfusion in the murine mandible.
AB  - Purpose Biomechanical, densitometric, and histological analyses have been the
      mainstay for reproducible outcome measures for investigation of new bone
      formation and osseous healing. Here we report the addition of radiomorphometric
      vascular analysis as a quantitative measure of vascularity in the murine
      mandible. To our knowledge this is the first description of using micro-computed
      tomography (micro-CT) to evaluate the temporal and spatial pattern of
      angiogenesis in the craniofacial skeleton. Methods The vessel perfusion technique
      was performed on 10 Sprague-Dawley rats using Microfil (MV-122, Flow Tech;
      Carver, MA). After decalcification, hemimandibles were imaged using high
      resolution micro-CT. Six separate radiomorphometric vascular metrics were
      calculated. Results Radiomorphometric values were analyzed using three different
      thresholds on micro-CT. Experimentally, 1000 Hounsfield units was found to be the
      optimal threshold for analysis to capture the maximal vascular content of the
      bone. Data from seven hemimandibles were analyzed. Minimal statistical variance
      in each of the quantitative measures of vascularity resulted in reproducible
      metrics for each of the radiomorphometric parameters. Conclusions We have
      demonstrated that micro-CT vascular imaging provides a robust methodology for
      evaluation of vascular networks in the craniofacial skeleton. This technique
      provides 3D quantitative data analysis that differs significantly from laser
      Doppler and microsphere methods, which simply measure flow. This technique is
      advantageous over labor-intensive 2D conventional analyses using histology and X
      ray microangiography. Our data establish the appropriate thresholding for optimal
      vascular analyses and provide baseline measurements that can be used to analyze
      the role of angiogenesis in bone regeneration and repair in the craniofacial
      skeleton. 

PMID- 24294406
TI  - An analysis of malar fat volume in two age groups: implications for craniofacial
      surgery.
AB  - Objective To evaluate how malar fat pad (MFP) volumes vary with age, after
      controlling for gender and body mass index (BMI). Study Design A prospective case
      control study evaluating volume of the MFP in women of two age groups. Methods
      Soft tissue dimensions were measured in eight subjects using magnetic resonance
      imaging. A multiplanar localizing sequence, followed in sagittal and coronal
      orientations using a turbo spin echo sequence, was performed to define the MFP.
      Volumetric calculations were then performed using a 3D image analysis application
      (Dextroscope, Volume Interactions, Republic of Singapore) to circumscribe areas,
      orient dimensions, and calculate volumes of the MFP. Results These data reveal no
      significant difference in the mean (standard deviation) right MFP (p = 0.50),
      left MFP (p = 0.41), or total MFP (p = 0.45) volumes when comparing the two age
      groups. In addition, these data indicate that there was no correlation between
      age and total MFP volume (Pearson correlation coefficient 0.27). Moreover, there
      was no correlation between age and the ratio of total volume/BMI (Pearson
      correlation coefficient -0.18). Conclusions Although the sample size of this
      study was small, these data indicate that ptosis of midfacial fat is more
      important than volume loss in midfacial aging. These data would suggest
      repositioning as the primary modality for craniofacial reconstruction. 

PMID- 24294407
TI  - Iatrogenic oculocardiac reflex in a patient with head injury.
AB  - A 16-year-old girl with a history of a recent fall from the third floor was
      transferred to the emergency room. On presentation, the patient, who had
      sustained multiple facial fractures, was in clinical shock with a blood pressure
      80/40 mm Hg, heart rate 130/min, tachypnea (>30/min), Po2 50 mm Hg, and So2 82%,
      and she was intubated for airway protection. Severe nasal hemorrhage was detected
      (hematocrit: 22%), therefore a bilateral anteroposterior balloon nasal catheter
      was inserted and inflated with air. Bleeding was controlled. A few minutes later,
      her heart rate dropped to 40/min. Atropine was administered intravenously and the
      rate increased to 60/min. Computed tomography of the head revealed brain and
      subarachnoid hemorrhage, multiple fractures of the facial skeleton, and a round
      foreign body, full of air, compressing the left eye. The medial wall and the
      floor of the ipsilateral orbit were also fractured, establishing a naso-orbital
      communication. The left catheter was immediately removed. Heart rate was restored
      to normal. Facial fractures were addressed surgically. Patient's vision is
      intact. 

PMID- 24294408
TI  - A rare case of multiple oblique facial clefts with supernumerary teeth: case
      report.
AB  - Oblique facial clefts are rare congenital anomalies that can present alone or in
      association with other craniofacial anomalies. A high degree of clefting in the
      embryo may lead to hyperdontia secondary to dichotomy of the dental lamina.
      Multiple facial clefts with hyperdontia are clinically challenging and demand
      comprehensive rehabilitation. This article reports a case of multiple oblique
      facial clefts of variable severity with multiple supernumerary teeth in a 12-year
      old boy. The varied clinical presentation along with the rarity of the occurrence
      mandate documentation. 

PMID- 24294409
TI  - Investigation of severe craniomaxillofacial battle injuries sustained by u.s.
      Service members: a case series.
AB  - This case series describes craniomaxillofacial battle injuries, currently
      available surgical techniques, and the compromised outcomes of four service
      members who sustained severe craniomaxillofacial battle injuries in Iraq or
      Afghanistan. Demographic information, diagnostic evaluation, surgical procedures,
      and outcomes were collected and detailed with a follow-up of over 2 years.
      Reconstructive efforts with advanced, multidisciplinary, and multiple revision
      procedures were indicated; the full scope of conventional surgical options and
      resources were utilized. Patients experienced surgical complications, including
      postoperative wound dehiscence, infection, flap failure, inadequate mandibular
      healing, and failure of fixation. These complications required multiple revisions
      and salvage interventions. In addition, facial burns complicated reconstructive
      efforts by delaying treatment, decreasing surgical options, and increasing
      procedural numbers. All patients, despite multiple surgeries, continue to have
      functional and aesthetic deficits as a result of their injuries. Currently, no
      conventional treatments are available to satisfactorily reconstruct the face
      severely ravaged by explosive devices to an acceptable level, much less to
      natural form and function. 

PMID- 24294410
TI  - Soft tissue coverage for mandibular fractures using two miniplates.
AB  - Recent reports have raised the concern that the two miniplate fixation technique
      for mandibular symphysis and body fractures may lead to greater complications
      than previously thought. However, it is possible that the surgical exposure and
      methods of soft tissue closure may be a major contributor to plate exposure. In
      this article, we detail a technique for vascularized tissue coverage of the
      hardware used to repair these mandibular fractures. We believe that this soft
      tissue coverage is crucial for minimizing complications associated with plate
      fixation. 

PMID- 24294411
TI  - Small-Molecule Allosteric Activation of Human Glucokinase in the Absence of
      Glucose.
AB  - Synthetic allosteric activators of human glucokinase are receiving considerable
      attention as potential diabetes therapeutic agents. Although their mechanism of
      action is not fully understood, structural studies suggest that activator
      association requires prior formation of a binary enzyme-glucose complex. Here, we
      demonstrate that three previously described activators associate with glucokinase
      in a glucose-independent fashion. Transient-state kinetic assays reveal a lag in
      enzyme progress curves that is systematically reduced when the enzyme is
      preincubated with activators. Isothermal titration calorimetry demonstrates that
      activator binding is enthalpically driven for all three compounds, whereas the
      entropic changes accompanying activator binding can be favorable or unfavorable.
      Viscosity variation experiments indicate that the kcat value of glucokinase is
      almost fully limited by product release, both in the presence and absence of
      activators, suggesting that activators impact a step preceding product release.
      The observation of glucose-independent allosteric activation of glucokinase has
      important implications for the refinement of future diabetes therapeutics and for
      the mechanism of kinetic cooperativity of mammalian glucokinase.

PMID- 24294413
TI  - You Can't Fix by Analysis What You've Spoiled by Design: Developing Survey
      Instruments and Collecting Validity Evidence.

PMID- 24294412
TI  - Spin-Noise-Detected Two-Dimensional Fourier-Transform NMR Spectroscopy.
AB  - We introduce two-dimensional NMR spectroscopy detected by recording and
      processing the noise originating from nuclei that have not been subjected to any
      radio frequency excitation. The method relies on cross-correlation of two noise
      blocks that bracket the evolution and mixing periods. While the sensitivity of
      the experiment is low in conventional NMR setups, spin-noise-detected NMR
      spectroscopy has great potential for use with extremely small numbers of spins,
      thereby opening a way to nanoscale multidimensional NMR spectroscopy.

PMID- 24294414
TI  - Residents teaching residents: how the duty hour limits have changed us.

PMID- 24294415
TI  - Duty hour reform through the eyes of neurological surgery residents.

PMID- 24294416
TI  - Self versus external assessment for technical tasks in surgery: a narrative
      review.
AB  - BACKGROUND: Self-assessment is an intricate component of continuing professional
      development and lifelong learning for health professionals. The agreement between
      self and external assessment for cognitive tasks in health professionals is
      reported to be poor; however, this topic has not been reviewed for technical
      tasks in surgery. OBJECTIVE: To compare self and external assessment for
      technical tasks in surgery. METHODS: MEDLINE, ERIC, and Google Scholar databases
      were searched for data from January 1960 to November 2011. Inclusion criteria
      were restricted to articles published in English in peer-reviewed journals, which
      reported on a comparison between self and external assessment for a technical
      task in a surgical specialty and involved medical students, surgical residents,
      surgical fellows, or practicing surgeons. Abstracts of identified articles were
      reviewed and pertinent full-text versions were retrieved. Manual searching of
      bibliographies for additional studies was performed. Data were extracted in a
      systematic manner. RESULTS: From a total of 49 citations, 17 studies (35%) were
      selected for review. Eight of the 17 studies (47%) reported no agreement, whereas
      9 studies (53%) reported an agreement between self and external assessment for
      technical tasks in surgery. Four studies (24%) reported higher self versus
      external assessment scores, whereas 3 studies (18%) reported lower self versus
      external assessment scores. Sixteen studies (94%) focused on retrospective self
      assessment and 1 study (6%) focused on predictive self-assessment. Agreement
      improved with higher levels of participant training; with high-quality, timely,
      and relevant feedback; and with postprocedure video review. CONCLUSIONS: This
      review demonstrated mixed results regarding an agreement between self and
      external assessment scores for technical tasks in surgery. Future investigations
      should attempt to improve the study design by accounting for differences between
      men and women, conducting paired and independent mean comparisons of self and
      external assessments, and ensuring that external assessments are valid and
      reliable.

PMID- 24294417
TI  - Barriers to Implementing the ACGME Outcome Project: A Systematic Review of
      Program Director Surveys.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME)
      introduced the Outcome Project in July 2001 to improve the quality of resident
      education through competency-based learning. The purpose of this systematic
      review is to determine and explore the perceptions of program directors regarding
      challenges to implementing the ACGME Outcome Project. METHODS: We used the PubMed
      and Web of Science databases and bibliographies for English-language articles
      published between January 1, 2001, and February 17, 2012. Studies were included
      if they described program directors' opinions on (1) barriers encountered when
      attempting to implement ACGME competency-based education, and (2) assessment
      methods that each residency program was using to implement competency-based
      education. Articles meeting the inclusion criteria were screened by 2
      researchers. The grading criterion was created by the authors and used to assess
      the quality of each study. RESULTS: The survey-based data reported the opinions
      of 1076 program directors. Barriers that were encountered include: (1) lack of
      time; (2) lack of faculty support; (3) resistance of residents to the Outcome
      Project; (4) insufficient funding; (5) perceived low priority for the Outcome
      Project; (6) inadequate salary incentive; and (7) inadequate knowledge of the
      competencies. Of the 6 competencies, those pertaining to patient care and medical
      knowledge received the most responses from program directors and were given
      highest priority. CONCLUSIONS: The reviewed literature revealed that time and
      financial constraints were the most important barriers encountered when
      implementing the ACGME Outcome Project.

PMID- 24294418
TI  - Influence of clinical experience and productivity on emergency medicine faculty
      teaching scores.
AB  - BACKGROUND: Commonly cited barriers to effective teaching in emergency medicine
      include lack of time, competing demands for patient care, and a lack of formal
      teaching experience. Teaching may be negatively affected by demands for increased
      clinical productivity, or positively influenced by clinical experience.
      OBJECTIVE: To examine the association between faculty teaching scores and
      clinical productivity, years of clinical experience, and amount of clinical
      contact with resident physicians. METHODS: We conducted a retrospective,
      observational study with existing data on full-time faculty at a high-volume,
      urban emergency medicine residency training program for academic year 2008-2009.
      Residents rated faculty on 9 domains of teaching, including willingness to teach,
      enthusiasm for teaching, medical knowledge, preparation, and communication.
      Clinical productivity data for relative value units per hour and number of
      patients per hour, years of clinical experience, and annual clinical hours were
      obtained from existing databases. RESULTS: For the 25 core faculty members
      included in the study, there was no relationship between faculty teaching scores
      and clinical productivity measures (relative value units per hour: r (2)  = 
      0.01, P  =  .96, patients per hour: r (2)  =  0.00, P  =  .76), or between
      teaching scores and total clinical hours with residents (r (2)  =  0.07, P  = 
      .19). There was a significant negative relationship between years of experience
      and teaching scores (r (2)  =  0.27, P < .01). CONCLUSIONS: Our study
      demonstrated that teaching scores for core emergency medicine faculty did not
      correlate with clinical productivity or amount of clinical contact with
      residents. Teaching scores were inversely related to number of years of clinical
      experience, with more experienced faculty earning the lowest teaching scores.
      Further study is necessary to determine if there are clinical measures that
      identify good educators.

PMID- 24294419
TI  - Systems-based content in medical morbidity and mortality conferences: a decade of
      change.
AB  - BACKGROUND: Following the Accreditation Council for Graduate Medical Education
      recommendations in 1999 to foster education in the systems-based practice (SBP)
      competency by examining adverse clinical events, institutions have modified the
      morbidity and mortality conference (MMC) to increase SBP-related discussion. We
      sought to examine the extent to which SBP-related content has increased in our
      department's MMCs compared with MMCs 10 years prior. METHOD: We qualitatively
      analyzed audio recordings of our MMCs during 2 academic years, 1999-2000 (n  = 
      30) and 2010-2011 (n  =  30). We categorized comments and questions from
      moderators and faculty as SBP or non-SBP and characterized conferences by whether
      adverse events were presented and which systems issues were discussed. RESULTS:
      Compared with MMCs in 1999-2000, present-day MMCs included a greater average
      percentage of SBP comments stated (69% versus 12%; P <= .001) and questions asked
      (13% versus 1%; P  =  .001) by the moderator, SBP comments stated (44% versus 4%;
      P <= .001) and questions asked (19% versus 1%; P <= .001) by faculty, and were
      more likely to present adverse events (87% versus 13%; P < .001). Interrater
      reliability for the distinction between SBP and non-SBP content was good (kappa 
      =  0.647). Most common categories of systems issues discussed in 2010-2011 were
      critical laboratory value processing and reporting, institutional policies, and
      hospital-based factors. CONCLUSIONS: Over the past decade, our MMC has
      transformed to include more discussion of SBP-related content and adverse events.
      The MMC can be used to educate residents in SBP and can also serve as a
      cornerstone for departmental quality and safety initiatives.

PMID- 24294420
TI  - Self-assessment on the competencies and reported improvement priorities for
      pediatrics residents.
AB  - BACKGROUND: Self-assessment and self-directed learning are essential to becoming
      an effective physician. OBJECTIVE: To identify factors associated with resident
      self-assessment on the competencies, and to determine whether residents chose
      areas of self-assessed relative weakness as areas for improvement in their
      Individualized Learning Plan (ILP). METHODS: We performed a cross-sectional
      analysis of the American Academy of Pediatrics' PediaLink ILP database.
      Pediatrics residents self-assessed their competency in the 6 Accreditation
      Council for Graduate Medical Education competencies using a color-coded slider
      scale with end anchors "novice" and "proficient" (0-100), and then chose at least
      1 competency to improve. Multivariate regression explored the relationship
      between overall confidence in core competencies, sex, level of training, and
      degree (MD or DO) status. Correlation examined whether residents chose to improve
      competencies in which they rated themselves as lower. RESULTS: A total of 4167
      residents completed an ILP in academic year 2009-2010, with residents' ratings
      improving from advanced beginner (48 on a 0-100 scale) in postgraduate year-1
      residents (PGY-1s) to competent (75) in PGY-3s. Residents rated themselves as
      most competent in professionalism (mean, 75.3) and least competent in medical
      knowledge (mean, 55.8) and systems-based practice (mean, 55.2). In the adjusted
      regression model, residents' competency ratings increased by level of training
      and whether they were men. In PGY-3s, there was no difference between men and
      women. Residents selected areas for improvement that correlated to competencies
      where they had rated themselves lower (P < .01). CONCLUSION: Residents' self
      assessment of their competencies increased by level of training, although
      residents rated themselves as least competent in medical knowledge and systems
      based practice, even as PGY-3s. Residents tended to choose subcompetencies, which
      they rated as lower to focus on improving.

PMID- 24294421
TI  - A thematic review of resident commentary on duty hours and supervision
      regulations.
AB  - BACKGROUND: The implementation on July 1, 2011, of new Accreditation Council for
      Graduate Medical Education (ACGME) standards for resident supervision and duty
      hours has prompted considerable debate about the potential positive and negative
      effects of these changes on patient care and resident education. A recent large
      sample study analyzed resident responses to these changes, using a Likert scale
      response. In this same study, 874 residents also provided free-text comments,
      which provide added insight into resident perspectives on duty hours and
      supervision. METHODS: A mixed-methods quantitative and qualitative survey of
      residents was conducted in August 2010 to assess resident perceptions of the
      proposed ACGME regulations. Common concerns in the residents' free responses were
      synthesized and quantified using content analysis, a common method for
      qualitative research. RESULTS: A total of 11 617 residents received the survey.
      Completed surveys were received from 2561 residents (22.0%), with 874 residents
      (34.1%) providing free-text responses. Most residents (83.0%) expressed
      unfavorable opinions about the new standards. The most frequently cited concerns
      included coverage issues, and a negative impact on patient care and education, as
      well as lack of preparation for senior roles. A smaller portion of residents
      commented they thought the standards would contribute to improvements in quality
      of life (36.1%) and patient care (4.9%). CONCLUSIONS: ACGME standards are
      important for graduate medical education, and their aim is to promote high
      quality education and better care to patients in teaching institutions. Yet, many
      residents are concerned about the day-to-day impact of the 2011 regulations, in
      particular the 16-hour duty period for interns. Most residents who provided free
      text responses had a negative impression of the new ACGME regulations. Residents'
      resistance to duty hour changes may represent a realization that residents are
      losing a central role in patient care. The concerns identified in this study
      demonstrate important issues for administrators and policymakers. Resident ideas
      and opinions should be considered in future revisions of ACGME requirements.

PMID- 24294422
TI  - Impact of web-based review on long-term retention of simulation-acquired knee and
      shoulder aspiration and injection skills.
AB  - BACKGROUND: Musculoskeletal problems are the reason for one-quarter of primary
      care visits. Opportunities for internal medicine residents to perform joint
      aspirations and injections have declined. Simulation has been shown to improve
      procedure skills post completion of simulation courses, yet controversy exists
      about the durability of simulation-acquired skills. OBJECTIVE: To investigate
      whether web-based review preserves residents' joint procedure skills 6 to 30
      months after a simulation course. METHODS: Postgraduate year-1 internal medicine
      residents participated in a simulation-based Joint Aspiration Injection Course
      consisting of web-based instructional material, guided practice on joint models,
      and a multiple-choice test. Procedure proficiency was scored by using a 3
      component skills checklist. Six to 30 months later, residents who had
      participated in the simulation were randomly assigned to review or not to review
      the original web-based instructional material before retesting. The groups were
      compared by using Wilcoxon rank sum and matched pairs signed rank tests. RESULTS:
      Compared to the performance at the end of the simulation course, scores of all 3
      procedure components declined (informed consent, 64.7-43.0 versus 30.6-23.8, P <
      .001; procedure proficiency, 63.4-61.7 versus 46.4-44.3, P < .001; and
      postprocedure instructions, 58.0-54.1 versus 29.9-29.4, P < .001). However, the
      review group outperformed the nonreview group on informed consent (shoulder: 37.1
      versus 24.6, P  =  .01) and postprocedure instructions (shoulder: 34.0 versus
      25.2, P  =  .01; knee: 35.5 versus 24.8, P < .001). Residents who reported doing
      actual procedures maintained a higher confidence level, compared with those
      reporting none (6.8-5.1 versus 4.1-3.6, P < .001). CONCLUSION: Shoulder and knee
      simulation-acquired skills declined 6 to 30 months after a simulation course.
      However, rereview of web-based instructional material improved proficiency in
      informed consent, shoulder, and postprocedure instructions, shoulder and knee.

PMID- 24294423
TI  - An observational study of hospital paging practices and workflow interruption
      among on-call junior neurological surgery residents.
AB  - BACKGROUND: Previous studies suggest that nonurgent pages comprise a substantial
      portion of the pages received by residents while on duty. We evaluated the
      number, type, and urgency of pages received and the task being performed at the
      time of paging by on-call junior neurosurgery residents at a large teaching
      hospital, with the aim of providing insight into mechanisms that can be developed
      to improve paging patterns and ultimately reduce physician distractions due to
      nonurgent communications. METHODS: For eight 12-hour call sessions, a medical
      student shadowed the on-call junior neurosurgery resident and recorded all pages
      received and the time, paging number and location, priority of the page
      (nonurgent, urgent, or emergency), and the activity the resident performed when
      the page was received. During one 5-hour session, a recorder measured the amount
      of time spent returning pages. RESULTS: During the study period, 439
      communications were recorded (mean of 54.9 per 12-hour session; range, 33-75).
      Communications occurred at a rate of every 13 minutes and ranged from every 34
      minutes to every 8.7 minutes. Paging remained frequent even during the hours when
      on-call residents are most likely to sleep (2-5 am), with an average of 4
      communications per hour. The time to return pages ranged from 15 to 174 seconds
      (mean, 79.7 seconds). Most pages were nonurgent (68.3%) and occurred during
      patient care activities (65%). CONCLUSIONS: Paging communications were frequent.
      Most pages were nonurgent and were received during important patient care
      activities. This suggests that a viable solution must address the work context of
      the individual being paged and the individual initiating the page to ensure that
      urgent communications are properly prioritized and attended to.

PMID- 24294424
TI  - Resident perceptions of service versus clinical education.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education states that
      education needs to have priority over service. There is a potential for residents
      to have a negative perception of activities termed service. OBJECTIVE: To
      understand how residents of one obstetrics and gynecology program conceptualize
      service and clinical education in their daily training experiences. METHODS: We
      conducted a qualitative survey using semistructured interviews with 9 residents
      in obstetrics and gynecology. Verbatim transcripts underwent phenomenologic
      analysis for themes and statements exemplifying the essence and nuances of
      residents' experiences. RESULTS: The conceptualization of service and clinical
      education encompassed 6 categories, with some overlap between terms. The category
      education encompassed (1) tasks and situations with some educational value termed
      indirect patient care; (2) tasks and situations with high educational values
      subdivided into direct patient care and teacher-learner interactions; and (3)
      traditional educational activities, including reflection. Service denoted: (1)
      tasks and situations with little to no educational value subdivided into indirect
      and direct patient care categories; (2) tasks and situations with some
      educational value described as direct patient care; and (3) community service to
      patients and communities. CONCLUSIONS: Definitions and the relative educational
      value of service and clinical education experiences overlapped considerably, but
      they varied by systematic, environmental, and personal factors. Service was used
      interchangeably to connote negative experiences that interfered with educational
      goals and positive experiences at the core of the profession's higher calling,
      the raison d'etre of many physicians. The community needs to agree on the
      definitions of these terms and clarify the meaning of an appropriate balance.

PMID- 24294425
TI  - Effect of procedure simulation workshops on resident procedural confidence and
      competence.
AB  - BACKGROUND: Pediatrics residents perform a limited number of some procedures in
      the clinical setting and may benefit from procedure simulation workshops.
      OBJECTIVE: To examine (1) the number and types of procedures performed by
      pediatrics residents in the clinical setting, (2) the relationship between the
      number of procedures performed and self-reported procedural confidence and
      competence, and (3) the effect of a procedure simulation workshop on self
      reported procedural confidence and competence. METHODS: Pediatrics residents at
      Lucile Packard Children's Hospital at Stanford attended a half-day procedure
      workshop, rotating between 6 procedure simulation stations: vascular access,
      airway management, bladder catheterization, chest tube placement, lumbar
      puncture, and umbilical lines. Residents completed a survey immediately before
      and after the workshop to self-assess procedural confidence and competence.
      RESULTS: Seventy-two residents participated in a procedure workshop. The average
      number of procedures performed increased significantly from intern to junior to
      senior year. A positive correlation was found between number of procedures
      performed and preworkshop confidence (P < .001, R (2)  =  0.86) and competence (P
      < .001, R (2)  =  0.88). For each procedure assessed, completion of the procedure
      simulation workshop resulted in a statistically significant (P < .001) increase
      in self-perceived confidence (14%-131%; average, 48%) and competence (12%-119%;
      average, 50%). Statistically significant (P < .05) increases remained when
      results for interns, juniors, and seniors were examined separately. CONCLUSION:
      Procedure simulation workshops improve resident self-reported procedural
      confidence and competence, particularly for procedures that are least performed.

PMID- 24294426
TI  - Medical students' perception of residents as teachers: comparing effectiveness of
      residents and faculty during simulation debriefings.
AB  - BACKGROUND: Simulation can enhance undergraduate medical education. However, the
      number of faculty facilitators needed for observation and debriefing can limit
      its use with medical students. The goal of this study was to compare the
      effectiveness of emergency medicine (EM) residents with that of EM faculty in
      facilitating postcase debriefings. METHODS: The EM clerkship at Indiana
      University School of Medicine requires medical students to complete one 2-hour
      mannequin-based simulation session. Groups of 5 to 6 students participated in 3
      different simulation cases immediately followed by debriefings. Debriefings were
      led by either an EM faculty volunteer or EM resident volunteer. The Debriefing
      Assessment for Simulation in Healthcare (DASH) participant form was completed by
      students to evaluate each individual providing the debriefing. RESULTS: In total,
      273 DASH forms were completed (132 EM faculty evaluations and 141 EM resident
      evaluations) for 7 faculty members and 9 residents providing the debriefing
      sessions. The mean total faculty DASH score was 32.42 and mean total resident
      DASH score was 32.09 out of a possible 35. There were no statistically
      significant differences between faculty and resident scores overall (P  =  .36)
      or by case type (P trauma  =  .11, P medical  =  .19, P pediatrics  =  .48).
      CONCLUSIONS: EM residents were perceived to be as effective as EM faculty in
      debriefing medical students in a mannequin-based simulation experience. The use
      of residents to observe and debrief students may allow additional simulations to
      be incorporated into undergraduate curricula and provide valuable teaching
      opportunities for residents.

PMID- 24294427
TI  - Pilot program using medical simulation in clinical decision-making training for
      internal medicine interns.
AB  - BACKGROUND: The use of high-fidelity medical simulation in cognitive skills
      training within internal medicine residency programs remains largely unexplored.
      OBJECTIVE: To design a pilot study to introduce clinical decision-making training
      using simulation into a large internal medicine residency program, explore the
      practicability of using junior and senior residents as facilitators, and examine
      the feasibility of using the program to improve interns' clinical skills.
      METHODS: Interns on outpatient rotations participated in a simulation curriculum
      on a voluntary basis. The curriculum consisted of 8 cases focusing on acute
      clinical scenarios encountered on the wards. One-hour sessions were offered twice
      monthly from August 2010 to February 2011. Internal medicine residents and
      simulation faculty served as facilitators. RESULTS: A total of 36 of 75 total
      interns volunteered to participate in the program, with 42% attending multiple
      sessions. Of all participants, 88% rated the sessions as "excellent," 97% felt
      that the program improved their ability to function as an intern and generate a
      plan, and 81% reported improvement in differential diagnosis skills. CONCLUSIONS:
      Simulation training was well received by the learners and improved self-reported
      clinical skills. Using residents as facilitators, supervised by faculty, was well
      received by the learners and enabled the implementation of the curriculum in a
      large training program. Simulation can provide opportunities for deliberate
      practice, and learners perceive this modality to be effective.

PMID- 24294428
TI  - An incremental approach to improving scholarly activity.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education requires
      scholarly activity for both faculty and residents in obstetrics and gynecology
      (Ob-Gyn). There is little evidence on the most effective method to train,
      recruit, and retain research faculty who can mentor resident researchers at small
      programs. INNOVATION: To address this problem, we created the "Baby Steps"
      program for a small university-based Ob-Gyn program. METHODS: After a thorough
      assessment of existing resources, a postdoctoral researcher was recruited and
      coupled with an established researcher to raise the standards of resident
      research, facilitate and coordinate resident projects, and support clinical
      faculty participation in research activities. Grant submissions, grants awarded,
      publications submitted, presentations, and awards were tracked before and after
      the implementation of the Baby Steps program for faculty and residents. RESULTS:
      After 2 years the program has already begun to show an increase in scholarly
      activity. In a program of 12 residents, 8 made one or more presentations at
      regional or national meetings within the previous 24 months. Additionally, 8 of
      12 clinical faculty members were engaged as mentors in resident research,
      compared with only 3 in past years. Further, abstract, paper, and grant
      submissions by faculty increased approximately 25%. CONCLUSION: The addition of a
      mentored postdoctoral researcher was associated with improvements to both
      resident and faculty research activities. Based on this success, a sister
      residency program has incorporated the Baby Steps approach into its training.

PMID- 24294429
TI  - A Citation Tracking System to Facilitate Sponsoring Institution Oversight of
      ACGME-Accredited Programs.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      requires the graduate medical education committee and the designated
      institutional official to ensure that citations for noncompliance with the
      accreditation standards and institutional trends in citations are reviewed and
      corrected. OBJECTIVE: To describe a citation tracking system (CTS) that uses
      Microsoft Office Access to efficiently catalogue, monitor, and document
      resolution of citations. INNOVATION: The CTS was implemented in a sponsoring
      institution with oversight of 133 ACGME-accredited programs. The designated
      institutional official and the graduate medical education committee review all
      program letters of notification and enter citations into the CTS. A program
      correction plan is required for each citation and is entered into the database.
      Open citations and action plans are reviewed by the graduate medical education
      committee and the designated institutional official on a quarterly basis, with
      decisions ranging from "closing" the citation to approving the action plan in
      process to requiring a new or modified action plan. Citation categories and
      subcategories are accessed on the ACGME website and entered into the CTS to
      identify trends. RESULTS: All 236 citations received since the 2006 Mayo School
      of Graduate Medical Education institutional site visit were entered into the CTS.
      On November 22, 2011, 26 of 236 citations (11%) were in active status with
      ongoing action plans, and 210 (89%) citations had been resolved and were closed.
      CONCLUSIONS: The CTS uses commercially available software to ensure citations are
      monitored and addressed and to simplify analysis of citation trends. The approach
      requires minimal staff time for data input and updates and can be performed
      without institutional information technology assistance.

PMID- 24294430
TI  - System-based approach to educating internal medicine residents on preventable
      hospital readmissions.
AB  - BACKGROUND: A literature gap exists in educating internal medicine residents
      about hospital readmissions and how to prevent them. INTERVENTION: The study
      aimed to implement a readmissions education initiative for general internal
      medicine inpatient resident teams in 3 general practice units at an urban,
      tertiary hospital. METHODS: Senior residents were given access to a daily list of
      readmissions, used a readmission assessment tool to investigate causes and to
      assess whether each readmission was preventable, led a monthly general practice
      unit team meeting to discuss each case, and presented their findings at the
      monthly multidisciplinary readmissions meeting for additional feedback. For
      program evaluation, we hypothesized that the "preventable" readmissions count
      tracked via the readmissions assessment tool would increase as residents became
      better educated on the root causes of readmissions. We also conducted a survey to
      assess perception of the readmissions education initiative. RESULTS:
      "Preventable" readmissions increased from 21% for the first 3 months of the
      intervention (September-November 2010) to 46% for the most recent 3 months
      (January-March 2011). The survey showed that 98% (41 of 42) of respondents who
      had attended a multidisciplinary readmissions meeting felt involved in an effort
      to review or improve the rate of hospital readmissions, whereas only 40% (21 of
      53) of the group that never attended a session shared the same answer.
      CONCLUSIONS: This initiative required few resources, and it appeared to help
      residents identify "preventable" reasons for readmissions, as well as increased
      their perceptions of being actively involved in reducing hospital readmissions.
      The intervention was not associated with a statistically significant reduction in
      readmissions, which may be influenced primarily by multiple factors outside
      residents' control.

PMID- 24294431
TI  - Quality and safety training in primary care: making an impact.
AB  - PURPOSE: Preparing residents for future practice, knowledge, and skills in
      quality improvement and safety (QI/S) is a requisite element of graduate medical
      education. Despite many challenges, residency programs must consider new
      curricular innovations to meet the requirements. We report the effectiveness of a
      primary care QI/S curriculum and the role of the chief resident in quality and
      patient safety in facilitating it. METHOD: Through the Veterans Administration
      Graduate Medical Education Enhancement Program, we added a position for a chief
      resident in quality and patient safety, and 4 full-time equivalent internal
      medicine residents, to develop the Primary Care Interprofessional Patient
      Centered Quality Care Training Curriculum. The curriculum includes a first-or
      second-year, 1-month block rotation that serves as a foundational experience in
      QI/S and interprofessional care. The responsibilities of the chief resident in
      quality and patient safety included organizing and teaching the QI/S curriculum
      and mentoring resident projects. Evaluation included prerotation and postrotation
      surveys of self-assessed QI/S knowledge, abilities, skills, beliefs, and
      commitment (KASBC); an end-of-the-year KASBC; prerotation and postrotation
      knowledge test; and postrotation and faculty surveys. RESULTS: Comparisons of
      prerotation and postrotation KASBC indicated significant self-assessed
      improvements in 4 of 5 KASBC domains: knowledge (P < .001), ability (P < .001),
      skills (P < .001), and belief (P < .03), which were sustained on the end-of-the
      year survey. The knowledge test demonstrated increased QI/S knowledge (P  = 
      .002). Results of the postrotation survey indicate strong satisfaction with the
      curriculum, with 76% (25 of 33) and 70% (23 of 33) of the residents rating the
      quality and safety curricula as always or usually educational. Most faculty
      members acknowledged that the chief resident in quality and patient safety
      enhanced both faculty and resident QI/S interest and participation in projects.
      CONCLUSIONS: Our primary care QI/S curriculum was associated with improved and
      persistent resident self-perceived knowledge, abilities, and skills and increased
      knowledge-based scores of QI/S. The chief resident in quality and patient safety
      played an important role in overseeing the curriculum, teaching, and providing
      leadership.

PMID- 24294432
TI  - Evaluation of a faculty development program aimed at increasing residents' active
      learning in lectures.
AB  - BACKGROUND: Active engagement in the learning process is important to enhance
      learners' knowledge acquisition and retention and the development of their
      thinking skills. This study evaluated whether a 1-hour faculty development
      workshop increased the use of active teaching strategies and enhanced residents'
      active learning and thinking. METHODS: Faculty teaching in a pediatrics residency
      participated in a 1-hour workshop (intervention) approximately 1 month before a
      scheduled lecture. Participants' responses to a preworkshop/postworkshop
      questionnaire targeted self-efficacy (confidence) for facilitating active
      learning and thinking and providing feedback about workshop quality. Trained
      observers assessed each lecture (3-month baseline phase and 3-month intervention
      phase) using an 8-item scale for use of active learning strategies and a 7-item
      scale for residents' engagement in active learning. Observers also assessed
      lecturer-resident interactions and the extent to which residents were asked to
      justify their answers. RESULTS: Responses to the workshop questionnaire (n  = 
      32/34; 94%) demonstrated effectiveness and increased confidence. Faculty in the
      intervention phase demonstrated increased use of interactive teaching strategies
      for 6 items, with 5 reaching statistical significance (P <= .01). Residents'
      active learning behaviors in lectures were higher in the intervention arm for all
      7 items, with 5 reaching statistical significance. Faculty in the intervention
      group demonstrated increased use of higher-order questioning (P  =  .02) and
      solicited justifications for answers (P  =  .01). CONCLUSION: A 1-hour faculty
      development program increased faculty use of active learning strategies and
      residents' engagement in active learning during resident core curriculum
      lectures.

PMID- 24294433
TI  - Experience-based guidance for implementing a direct observation checklist in a
      pediatric emergency department setting.
AB  - BACKGROUND: The importance and benefits of direct observation in residency
      training have been underscored by a number of studies. Yet, implementing direct
      observation in an effective and sustainable way is hampered by demands on
      physicians' time and shrinking resources for educational innovation. OBJECTIVE:
      To describe the development and pilot implementation of a direct observation tool
      to assess the history and physical examination skills of interns in a pediatric
      emergency department rotation. METHODS: A task force developed specific history
      and physical examination checklists for a range of common conditions. For the
      pilot implementation, 10 pediatric emergency medicine faculty attendings
      conducted the initial observations of 34 interns during the course of 1 academic
      year. At the conclusion of the pilot, the faculty observers and interns were
      interviewed to assess the feasibility and benefits of the process. RESULTS: A
      total of 33 of the 34 interns were observed during their rotation, with 26 of the
      observations conducted when the faculty observer was off shift, and it took
      approximately 20 minutes to complete each observation. In terms of learning
      benefits, interns and faculty observers reported that it facilitated clear and
      useful feedback and revealed gaps that would not have otherwise been identified.
      Faculty observers also mentioned that it helped them focus their teaching effort,
      built empathy with learners, and gave them a way to demonstrate a true concern
      for their learning. CONCLUSION: Our results offer evidence for the feasibility
      and benefits of the direct observation checklists. The description of the
      implementation, challenges, and response to those challenges may help others
      avoid some of the common problems faced when implementing direct observation
      methods.

PMID- 24294434
TI  - Anesthesiology Residents-as-Teachers Program: A Pilot Study.
AB  - BACKGROUND: The role of residents as teachers has grown over time. Programs have
      been established within various specialties to formally develop these skills.
      Anesthesiology residents are frequently asked to provide supervision for novice
      learners and have numerous opportunities for teaching skills and clinical
      decision making. Yet, there are no educational programs described in the
      literature to train anesthesiology residents to teach novice learners. OBJECTIVE:
      To explore whether a resident-as-teacher program would increase anesthesiology
      residents' self-reported teaching skills. METHODS: An 8-session interactive
      Anesthesiology Residents-as-Teachers (ART) Program was developed to emphasize 6
      key teaching skills. During a 2-year period, 14 anesthesiology residents attended
      the ART program. The primary outcome measure was resident self-assessment of
      their teaching skills across 14 teaching domains, before and 6 months after the
      ART program. Residents also evaluated the workshops for quality with a 9-item,
      postworkshop survey. Paired t testing was used for analysis. RESULTS: Resident
      self-assessment led to a mean increase in teaching skills of 1.04 in a 5-point
      Likert scale (P < .001). Residents reported the greatest improvement in
      writing/using teaching objectives (+1.29, P < .001), teaching at the bedside
      (+1.57, P  =  .002), and leading case discussions (+1.64, P  =  .001). Residents
      rated the workshops 4.2 out of 5 (3.9-4.7). CONCLUSIONS: Residents rated their
      teaching skills as significantly improved in 13 of 14 teaching domains after
      participation in the ART program. The educational program required few resources
      and was rated highly by residents.

PMID- 24294435
TI  - Internal medicine residents' computer use in the inpatient setting.
AB  - BACKGROUND: Studies have suggested that patient contact time for internal
      medicine residents is decreasing and being replaced with computer-related
      activities, yet objective data regarding computer use by residents are lacking.
      OBJECTIVE: The aim of this study was to objectively measure time use by internal
      medicine residents while on duty in the hospital setting using real-time, voice
      capture technology. METHODS: First- and third-year categoric internal medicine
      residents participated (n  =  25) during a 3-month period in 2010 while rotating
      on general internal medicine rotations. Portable speech-recognition technology
      was used to record residents' activities. The residents were prompted every 15
      minutes from an earpiece and asked to categorize the activity they had been doing
      since the last prompt, choosing from a predetermined list of 15 activities.
      RESULTS: Of the 1008 duty-time responses, 493 (49%) were classified as computer
      related activities, whereas 341 (34%) were classified as direct patient care, 110
      (11%) were classified as noncomputer-related education, and 64 (6%) were
      classified as other activities. Of resident reported computer-use time, 70% was
      spent on patient notes and order entry. CONCLUSIONS: The results of our study
      suggest that computer use is the predominant activity for internal medicine
      residents while in the inpatient setting. Work redesign because of duty hour
      regulations should consider how to free up residents' time from computer-based
      activities to allow residents to engage in more direct patient care and
      noncomputer-based learning.

PMID- 24294436
TI  - Patient communication during handovers between emergency medicine and internal
      medicine residents.
AB  - BACKGROUND: Communication failures are a key cause of medical errors and are
      particularly prevalent during handovers of patients between services. OBJECTIVE:
      To explore current perceptions of effectiveness in communicating critical patient
      information during admission handovers between emergency medicine (EM) residents
      and internal medicine (IM) residents. METHODS: Study design was a survey of IM
      and EM residents at a large urban hospital. Residents were surveyed about whether
      critical information was communicated during patient handovers. Measurements
      included comparisons between IM and EM residents about their perceptions of
      effective communication of key patient information and the quality of handovers.
      RESULTS: Ninety-three percent of EM residents (50 of 54) and 80% of IM residents
      (74 of 93) responded to the survey. The EM residents judged their handover
      performance to be better than how their IM colleagues assessed them on most
      questions. The IM residents reported that one-half of the time, EM residents
      provided organized and clear information, whereas EM residents self-reported that
      they did so most of the time (80%-90%). The IM residents reported that 25% of
      handovers were suboptimal and resulted in admission to an inappropriate level of
      care, and 10% led to harm or delay in care. The EM residents reported suboptimal
      communication was less common (5%). On the global assessment of whether the
      admission handover provided the information needed for good patient care, IM
      residents rated the quality of the handover data lower than did responding EM
      residents. CONCLUSIONS: There are gaps in communicating critical patient
      information during admission handovers as perceived by EM and IM residents. This
      information can form the basis for efforts to improve these handovers.

PMID- 24294437
TI  - Simulation in graduate medical education: understanding uses and maximizing
      benefits.

PMID- 24294438
TI  - A guide to writing peer-reviewed publications: a common program requirement and
      resume builder.

PMID- 24294439
TI  - Morbidity and mortality conferences: change you can believe in?

PMID- 24294440
TI  - Time to refine resident duty hour guidelines.

PMID- 24294441
TI  - Education and service: definitions are the easy part.

PMID- 24294442
TI  - Simulation-based curriculum: the breadth of applications in graduate medical
      education.

PMID- 24294443
TI  - Integrated care of refugees in a primary care residency clinic.

PMID- 24294444
TI  - The paradoxical influence of resident continuity clinic on primary care.

PMID- 24294445
TI  - Postures and Practice: A Yoga Student's Reflections.

PMID- 24294447
TI  - Next Accreditation System Time Line for Phase II.

PMID- 24294446
TI  - Defining scholarly activity in graduate medical education.
AB  - BACKGROUND: Scholarly activity is a requirement for accreditation by the
      Accreditation Council for Graduate Medical Education. There is currently no
      uniform definition used by all Residency Review Committees (RRCs). A total of 6
      of the 27 RRCs currently have a rubric or draft of a rubric to evaluate scholarly
      activity. OBJECTIVE: To develop a definition of scholarly activity and a set of
      rubrics to be used in program accreditation to reduce subjectivity of the
      evaluation of scholarly activity at the level of individual residency programs
      and across RRCs. METHODS: We performed a review of the pertinent literature and
      selected faculty promotion criteria across the United States to develop a
      structure for a proposed rubric of scholarly activity, drawing on work on
      scholarship by experts to create a definition of scholarly activity and rubrics
      for its assessment. RESULTS: The literature review showed that academic
      institutions in the United States place emphasis on all 4 major components of
      Boyer's definition of scholarship: discovery, integration, application, and
      teaching. We feel that the assessment of scholarly activity should mirror these
      findings as set forth in our proposed rubric. Our proposed rubric is intended to
      ensure a more objective evaluation of these components of scholarship in
      accreditation reviews, and to address both expectations for scholarly pursuits
      for core teaching faculty and those for resident and fellow physicians.
      CONCLUSION: The aim of our proposed rubric is to ensure a more objective
      evaluation of these components of scholarship in accreditation reviews, and to
      address expectations for scholarly pursuits for core teaching faculty as well as
      those for resident and fellow physicians.

PMID- 24294448
TI  - ACGME Awardees and Call for Nominations.

PMID- 24294449
TI  - Analysis of measurement accuracy for craniovertebral junction pathology : most
      reliable method for cephalometric analysis.
AB  - OBJECTIVE: This study was designed to determine the most reliable cephalometric
      measurement technique in the normal population and patients with basilar
      invagination (BI). METHODS: Twenty-two lateral radiographs of BI patients and 25
      lateral cervical radiographs of the age, sex-matched normal population were
      selected and measured on two separate occasions by three spine surgeons using six
      different measurements. Statistical analysis including intraclass correlation
      coefficient (ICC) was carried out using the SPSS software (V. 12.0). RESULTS:
      Redlund-Johnell and Modified (M)-Ranawat had a highest ICC score in both the
      normal and BI groups in the inter-observer study. The M-Ranawat method (0.83) had
      a highest ICC score in the normal group, and the Redlund-Johenll method (0.80)
      had a highest ICC score in the BI group in the intra-observer test. The McGregor
      line had a lowest ICC score and a poor ICC grade in both groups in the intra
      observer study. Generally, the measurement method using the odontoid process did
      not produce consistent results due to inter and intra-observer differences in
      determining the position of the odontoid tip. Opisthion and caudal point of the
      occipital midline curve are somewhat ambiguous landmarks, which induce variable
      ICC scores. CONCLUSION: On the contrary to other studies, Ranawat method had a
      lower ICC score in the inter-observer study. C2 end-plate and C1 arch can be the
      most reliable anatomical landmarks.

PMID- 24294450
TI  - Pre- and Post-Angioplasty Perfusion CT with Acetazolamide Challenge in Patients
      with Unilateral Cerebrovascular Stenotic Disease.
AB  - OBJECTIVE: Perfusion computed tomography (PCT) has the ability to measure
      quantitative value and produce maps of mean transit time (MTT), cerebral blood
      flow (CBF), and cerebral blood volume (CBV). We assessed cerebral hemodynamics by
      using these parameters and acetazolamide (ACZ) challenge for pre- and post
      procedural evaluation in patients with unilateral cerebrovascular stenotic
      disease. METHODS: Thirty patients underwent pre-procedural PCT with ACZ
      challenge, and 24 patients (80%) was conducted follow up PCT after angioplasty
      with same protocol. The mean MTT, CBF, and CBV were measured and compared in both
      middle cerebral arterial (MCA) territories before and after ACZ challenge.
      Hemispheric ratio and percent change after ACZ challenge were calculated before
      and after angioplasty. RESULTS: The mean stenosis rate was 76.6%. Significant
      increases in MTT (32.6%, p=0.000) and significant decreases in CBF (-14.2%,
      p=0.000) were found in stenotic side MCA territories. After ACZ challenge, there
      were significant changes in MTT (37.4%, p=0.000), CBF (-13.1%, p=0.000), and CBV
      (-10.5%, p=0.001) in pre-procedural perfusion study. However, no significant
      increases were found in MTT, or decreases in CBF and CBV in post-procedural
      study. There were no significant changes after ACZ challenge also. In addition,
      the degrees of these changes (before and after ACZ challenge) were highly
      correlated with the stenotic degrees in pre-procedural perfusion study.
      CONCLUSION: PCT with ACZ challenge appears to be a useful tool to assess the
      cerebral perfusion status especially in patients with unilateral symptomatic
      stenotic disease.

PMID- 24294451
TI  - Significance of C-reactive protein and transcranial Doppler in cerebral vasospasm
      following aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Cerebral vasospasm is a common and potentially devastating
      complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes
      seem to play a major role in the pathogenesis of vasospasm. C-reactive protein
      (CRP) constitutes a highly sensitive inflammatory marker. Elevation of serum CRP
      levels has been demonstrated in patients with aSAH. The purpose of the current
      study was to evaluate the possible relationship between CRP levels in the serum
      and transcranial Doppler (TCD) and the development of vasospasm in patients with
      aSAH. METHODS: A total of 61 adult patients in whom aSAH was diagnosed were
      included in the study from November 2008 to May 2011. The patients' demographics,
      Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography
      studies, and daily neurological examinations were recorded. Serial serum CRP
      measurements were obtained on days 1, 3, 5, 7, 9, 11 and 13 and TCD was measured
      on days 3, 5, 7, 9, 11 and 13. All patients underwent either surgical or
      endovascular treatment within 24 hours of their hemorrhagic attacks. RESULTS:
      Serum CRP levels peaked on the 3rd postoperative day. There were significant
      differences between the vasospasm group and the non-vasospasm group on the 1st,
      3rd and 5th day. There were significant differences between the vasospasm group
      and the non-vasospasm group on the 3rd day in the mean middle cerebral artery
      velocities on TCD. CONCLUSION: Patients with high levels of CRP on the 1st
      postoperative day and high velocity of mean TCD on the 3rd postoperative day may
      require closer observation to monitor for the development of vasospasm.

PMID- 24294452
TI  - Prognostic factors and clinical outcomes of acute intracerebral hemorrhage in
      patients with chronic kidney disease.
AB  - OBJECTIVE: We conducted a retrospective study examining the outcomes of
      intracerebral hemorrhage (ICH) in patients with chronic kidney disease (CKD) to
      identify parameters associated with prognosis. METHODS: From January 2001 to June
      2008, we treated 32 ICH patients (21 men, 11 women; mean age, 62 years) with CKD.
      We surveyed patients age, sex, underlying disease, neurological status using
      Glasgow Coma Scale (GCS), ICH volume, hematoma location, accompanying
      intraventricular hemorrhage, anti-platelet agents, initial and 3rd day systolic
      blood pressure (SBP), clinical outcome using the modified Rankin Scale (mRS) and
      complications. The severity of renal functions was categorized using a modified
      glomerular filtration rate (mGFR). Multifactorial effects were identified by
      regression analysis. RESULTS: The mean GCS score on admission was 9.4+/-4.4 and
      the mean mRS was 4.3+/-1.8. The overall clinical outcomes showed a significant
      relationship on initial neurological status, hematoma volume, and mGFR. Also, the
      outcomes of patients with a severe renal dysfunction were significantly different
      from those with mild/moderate renal dysfunction (p<0.05). Particularly, initial
      hematoma volume and sBP on the 3rd day after ICH onset were related with
      mortality (p<0.05). However, the other factors showed no correlation with
      clinical outcome. CONCLUSION: Neurological outcome was based on initial
      neurological status, renal function and the volume of the hematoma. In addition,
      hematoma volume and uncontrolled blood pressure were significantly related to
      mortality. Hence, the severity of renal function, initial neurological status,
      hematoma volume, and uncontrolled blood pressure emerged as significant
      prognostic factors in ICH patients with CKD.

PMID- 24294453
TI  - The usefulness of the ivy sign on fluid-attenuated intensity recovery images in
      improved brain hemodynamic changes after superficial temporal artery-middle
      cerebral artery anastomosis in adult patients with moyamoya disease.
AB  - OBJECTIVE: MR perfusion and single photon emission computerized tomography
      (SPECT) are well known imaging studies to evaluate hemodynamic change between
      prior to and following superficial temporal artery (STA)-middle cerebral artery
      (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness
      make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated
      inversion recovery (FLAIR) images in adult patients with moyamoya disease and
      compared it with result of SPECT and MR perfusion images. METHODS: We enrolled
      twelve patients (thirteen cases) who were diagnosed with moyamoya disease and
      underwent STA-MCA anastomosis at our medical institution during a period ranging
      from September of 2010 to December of 2012. The presence of the ivy sign on MR
      FLAIR images was classified as Negative (0), Minimal (1), and Positive (2).
      Regions were classified into four territories: the anterior cerebral artery
      (ACA), the anterior MCA, the posterior MCA and the posterior cerebral artery.
      RESULTS: Ivy signs on preoperative and postoperative MR FLAIR were improved (8
      and 4 in the ACA regions, 13 and 4 in the anterior MCA regions and 19 and 9 in
      the posterior MCA regions). Like this result, the cerebrovascular reserve (CVR)
      on SPECT was significantly increased in the sum of CVR in same regions after STA
      MCA anastomosis. CONCLUSION: After STA-MCA anastomosis, ivy signs were decreased
      in the cerebral hemisphere. As compared with conventional diagnostic modalities
      such as SPECT and MR perfusion images, the ivy sign on MR FLAIR is considered as
      a useful indicator in detecting brain hemodynamic changes between preoperatively
      and postoperatively in adult moyamoya patients.

PMID- 24294454
TI  - Clinical analysis of intracranial hemangiopericytoma.
AB  - OBJECTIVE: Intracranial hemangiopericytomas (HPCs) are rare tumors with
      aggressive behavior, including local recurrence and distant metastasis. We
      conducted this retrospective study to evaluate the efficacy of grossly total
      resection and adjuvant radiotherapy (RT) for these tumors. METHODS: A total of 13
      patients treated for intracranial HPC from January 1995 through May 2013 were
      included in this retrospective study. We analyzed the clinical presentations,
      radiologic appearances, treatment results, and follow-up outcomes, as well as
      reviewed other studies. RESULTS: The ages of the patients at the time of
      diagnosis ranged from 26 to 73 years (mean : 48 years). The majority of the
      patients were male (92.3%), and the majority of the tumors were located in the
      parasagittal and falx. The ratio of intracranial HPCs to meningiomas was 13 : 598
      in same period, or 2.2%. Seven patients (53.8%) had anaplastic HPCs. Nine
      patients (69.2%) underwent gross total tumor resection in the first operation
      without mortality. Eleven patients (84.6%) underwent postoperative adjuvant RT.
      Follow-up period ranged from 13 to 185 months (mean : 54.3 months). The local
      recurrence rate was 46.2% (6/13), and there were no distant metastases. The 10
      year survival rate after initial surgery was 83.9%. The initial mean Karnofsky
      performance scale (KPS) was 70.8 and the final mean KPS was 64.6. CONCLUSION:
      Gross total tumor resection upon initial surgery is very important. We believe
      that adjuvant RT is helpful even with maximal tumor resection. Molecular biologic
      analyses and chemotherapy studies are required to achieve better outcomes in
      recurrent intracranial HPCs.

PMID- 24294455
TI  - Feasibility of endoscopic endonasal approach for recurrent pituitary adenomas
      after microscopic trans-sphenoidal approach.
AB  - OBJECTIVE: The surgical approach for recurrent pituitary adenoma after trans
      sphenoidal approach (TSA) is challenging. We report the outcomes of the
      endoscopic TSA for recurrent pituitary adenoma after microscopic TSA. METHODS:
      From February 2010 to February 2013, endoscopic TSA was performed for removal of
      30 recurrent pituitary adenomas after microscopic TSA. Twenty-seven (90%)
      patients had a clinically non-functioning pituitary adenoma. Twenty-four (80%)
      patients suffered from a visual disturbance related to tumor growth. The clinical
      features and surgical outcomes were retrospectively analyzed for the
      ophthalmological, endocrinological, and oncological aspects. RESULTS: The mean
      tumor volume was 11.7 cm(3), and gross total resection was achieved in 50% of
      patients. The volumetric analysis based on the postoperative MR showed that the
      mean extent of resection rates were 90%. Vision was improved in 19 (79%) of 24
      patients with visual symptoms, and endocrinological cure was achieved in all of
      three functioning pituitary adenomas; however, the post-operative follow-up
      endocrinological examination revealed a new endocrinological deficit in one
      patient. Two patients required antibiotics management for post-operative
      meningitis. CONCLUSION: The endoscopic TSA can be an effective treatment option
      for recurrent pituitary adenoma after microscopic TSA with acceptable outcome.

PMID- 24294456
TI  - The efficacy and perioperative complications associated with lumbar spinal fusion
      surgery, focusing on geriatric patients in the republic of Korea.
AB  - OBJECTIVE: The purpose of this study was to examine the efficacy and
      perioperative complications associated with lumbar spinal fusion surgery,
      focusing on geriatric patients in the Republic of Korea. METHODS: We
      retrospectively investigated 485 patients with degenerative spinal diseases who
      had lumbar spinal fusion surgeries between March 2006 and December 2010 at our
      institution. Age, sex, comorbidity, American Society of Anesthesiologists (ASA)
      class, fusion segments, perioperative complications, and outcomes were analyzed
      in this study. Risk factors for complications and their association with age were
      analyzed. RESULTS: In this study, 81 patients presented complications (16.7%).
      The rate of perioperative complications was significantly higher in patients 70
      years or older than in other age groups (univariate analysis, p=0.015;
      multivariate analysis, p=0.024). The perioperative complications were not
      significantly associated with the other factors tested (sex, comorbidity, ASA
      class, and fusion segments). Post-operative outcomes of lumbar spinal fusion
      surgeries for the patients were determined on the basis of MacNab's criteria
      (average follow up period : 19.7 months), and 412 patients (85.0%) were
      classified as having "excellent" or "good" results. CONCLUSION: Increasing age
      was an important risk factor for perioperative complications in patients
      undergoing lumbar spinal fusion surgery, whereas other factors were not
      significant. However, patients' satisfaction or return to daily activities when
      compared with younger patients did not show much difference. We recommend good
      clinical judgment as well as careful selection of geriatric patients for lumbar
      spinal fusion surgery.

PMID- 24294457
TI  - Clinical outcome in gamma knife radiosurgery for metastatic brain tumors from the
      primary breast cancer : prognostic factors in local treatment failure and
      survival.
AB  - OBJECTIVE: Brain metastases in primary breast cancer patients are considerable
      sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained
      popularity as an up-front therapy in treating such metastases over traditional
      radiation therapy due to better neurocognitive function preservation. The aim of
      this study was to clarify the prognostic factors for local tumor control and
      survival in radiosurgery for brain metastases from primary breast cancer.
      METHODS: From March 2001 to May 2011, 124 women with metastatic brain lesions
      originating from a primary breast cancer underwent GKRS at a tertiary medical
      center in Seoul, Korea. All patients had radiosurgery as a primary treatment or
      salvage therapy. We retrospectively reviewed their clinical outcomes and
      radiological responses. The end point of this study was the date of patient's
      death or the last follow-up examination. RESULTS: In total, 106 patients (268
      lesions) were available for follow-up imaging. The median follow-up time was 7.5
      months. The mean treated tumor volume at the time of GKRS was 6273 mm(3) (range,
      4.5-27745 mm(3)) and the median dose delivered to the tumor margin was 22 Gy
      (range, 20-25 Gy). Local recurrence was assessed in 86 patients (216 lesions) and
      found to have occurred in 36 patients (83 lesions, 38.6%) with a median time of 6
      months (range, 4-16 months). A treated tumor volume >5000 mm(3) was significantly
      correlated with poor local tumor control through a multivariate analysis (hazard
      risk=7.091, p=0.01). Overall survival was 79.9%, 48.3%, and 15.3% at 6, 12, and
      24 months, respectively. The median overall survival was 11 months after GKRS
      (range, 6 days-113 months). Multivariate analysis showed that the pre-GKRS
      Karnofsky performance status, leptomeningeal seeding prior to initial GKRS, and
      multiple metastatic lesions were significant prognostic factors for reduced
      overall survival (hazard risk=1.94, p=0.001, hazard risk=7.13, p<0.001, and
      hazard risk=1.46, p=0.046, respectively). CONCLUSION: GKRS has shown to be an
      effective and safe treatment modality for treating brain metastases of primary
      breast cancer. Most metastatic brain lesions initially respond to GKRS, though,
      many patients have further CNS progression in subsequent periods. Patients with
      poor Karnofsky performance status and multiple metastatic lesions are at risk of
      CNS progression and poor survival, and a more frequent and strict surveillance
      protocol is suggested in such high-risk groups.

PMID- 24294458
TI  - Galeal tack-up sutures to prevent subgaleal cerebrospinal fluid collection.
AB  - OBJECTIVE: Postoperative subgaleal cerebrospinal fluid (CSF) collection is
      considered as one of the common minor surgical complication which can lead to
      prolonged hospitalization. We introduce "galeal tack-up suture" to prevent
      postoperative subgaleal CSF collection. METHODS: Galeal tack-up suture consists
      of various surgical techniques which aim to fix galea to cranium in order to
      prevent CSF pooling in subgaleal space. A total of 87 patients who underwent
      craniotomy were divided into two groups while closing the wound : group A with
      galeal tack-up suture and group B with routine wound closure without galeal tack
      up suture. The patients were observed for postoperative subgaleal CSF collection.
      RESULTS: Among 87 cranitomy cases, galeal tack-up suture was performed in 32
      cases and routine wound closure was done in 55 cases. Postoperative subgaleal CSF
      collection occurred in 13 cases (15%) in which 12 cases occurred in group B
      patients and 1 case occurred in group A patients (p=0.026). CONCLUSION: Galeal
      tack-up suture is an easy and effective technique in wound closure to prevent
      postoperative CSF collection.

PMID- 24294459
TI  - Supratentorial intracerebral schwannoma : its fate and proper management.
AB  - Intracerebral schwannomas are rare and there have been none reported in Korea. We
      present the case of a 25-year-old man with newly developed right-side weakness
      and recent seizure aggravation. His seizures started approximately 9 years prior
      to admission. At that time, a 1 cm diameter intra-axial enhancing mass at the
      left precentral gyrus was found on magnetic resonance image (MRI). After 9 years
      of observation and treatment with antiepileptic medication, an MRI taken due to
      symptom aggravation revealed peri-tumoral cyst formation with tumor enlargement.
      The tumor was surgically removed. Subsequently, right-side weakness diminished
      and there was good seizure control. Pathologic diagnosis was schwannoma.
      Schwannoma is a very rare tumor and there are no pathognomonic findings on
      radiologic images; thus, it is challenging to make a correct diagnosis. However,
      considering the natural course and excellent prognosis after surgical treatment
      of this kind of intra-axial mass with benign features, early surgery for
      diagnosis and proper treatment is highly recommended. 

PMID- 24294460
TI  - Delayed Retroperitoneal Hemorrhage due to Lumbar Artery Pseudoaneurysm after
      Lumbar Posterolateral Fusion.
AB  - A 55-year-old female patient presented with lower back pain and neurogenic
      intermittent claudication and underwent L3-L4 posterolateral fusion. To prepare
      the bone fusion bed, the transverse process of L3 and L4 was decorticated with a
      drill. On the 9th post-operative day, the patient complained of a sudden onset of
      severe abdominal pain and distension. Abdominal computed tomography revealed
      retroperitoneal hematoma in the right psoas muscle and iatrogenic right L3
      transverse process fracture. Lumbar spinal angiography showed the delayed
      hematoma due to rupture of the 2nd lumbar artery pseudoaneurysm and coil
      embolization was done at the ruptured lumbar artery pseudoaneusyrm. Since then,
      the patient's postoperative progress proceeded normally with recovery of the
      hemodynamic parameters. 

PMID- 24294461
TI  - Cervical Compressive Myelopathy due to Anomalous Bilateral Vertebral Artery.
AB  - We report a very rare case of cervical compressive myelopathy by an anomalous
      bilateral vertebral artery (VA) entering the spinal canal at the C1 level and
      compressing the spinal cord. A 70-year-old woman had been suffering from
      progressive gait disturbance. Magnetic resonance imaging revealed that a
      bilateral VA at the V4 segment had abnormal courses and caused compression to the
      high cervical cord. VA repositioning was performed by anchoring a suture between
      the artery and around the arachnoid membrane and dentate ligament, and then,
      microvascular decompression using a Teflon sponge was done between the VA and the
      spinal cord. The weakness in the patient improved in the lower extremity after
      the operation. Anomalous VA could be one of the rare causes of cervical
      compressive myelopathy. Additionally, an anchoring suture and microvascular
      decompression around the VA could be a sufficient and safe method to indirectly
      decompress the spinal canal. 

PMID- 24294462
TI  - Cystic giant sacral schwannoma mimicking aneurysmal bone cyst : a case report and
      review of literatures.
AB  - To present a rare case of a cystic giant schwannoma of the sacrum mimicking
      aneurysmal bone cyst (ABC). A 54-year-old man visited our institute complaining
      left leg weakness and sensory change for several years. Magnetic resonance
      imaging revealed a large multilocular cystic mass with canal invasion and bone
      erosion confined to left S1 body. The lesion showed multiple septal enhancement
      without definite solid component. Initially the tumor was considered as ABC. The
      patient underwent grossly-total tumor resection with lumbosacral reconstruction
      via posterior approach. The tumor was proved to be a cystic schwannoma. The
      postoperative course was uneventful and the patient was relieved from
      preoperative symptoms. We present a rare case of pure cystic giant schwannoma
      confined to sacrum mimicking ABC. The surgical treatment is challenging due to
      the complex anatomy of the sacrum. Schwannoma should be considered in the
      differential diagnosis of osteolytic sacral cysts. 

PMID- 24294463
TI  - Spinal extradural arachnoid cyst.
AB  - Spinal extradural arachnoid cyst (SEAC) is a rare disease and uncommon cause of
      compressive myelopathy. The etiology remains still unclear. We experienced 2
      cases of SEACs and reviewed the cases and previous literatures. A 59-year-old man
      complained of both leg radiating pain and paresthesia for 4 years. His MRI showed
      an extradural cyst from T12 to L3 and we performed cyst fenestration and repaired
      the dural defect with tailored laminectomy. Another 51-year-old female patient
      visited our clinical with left buttock pain and paresthesia for 3 years. A large
      extradural cyst was found at T1-L2 level on MRI and a communication between the
      cyst and subarachnoid space was illustrated by CT-myelography. We performed cyst
      fenestration with primary repair of dural defect. Both patients' symptoms
      gradually subsided and follow up images taken 1-2 months postoperatively showed
      nearly disappeared cysts. There has been no documented recurrence in these two
      cases so far. Tailored laminotomy with cyst fenestration can be a safe and
      effective alternative choice in treating SEACs compared to traditional complete
      resection of cyst wall with multi-level laminectomy. 

PMID- 24294464
TI  - Phrenic nerve stimulation for diaphragm pacing in a quadriplegic patient.
AB  - Chronic hypoventilation due to injury to the brain stem respiratory center or
      high cervical cord (above the C3 level) can result in dependence to prolonged
      mechanical ventilation with tracheostomy, frequent nosocomial pneumonia, and
      prolonged hospitalization. Diaphragm pacing through electrical stimulation of the
      phrenic nerve is an established treatment for central hypoventilation syndrome.
      We performed chronic phrenic nerve stimulation for diaphragm pacing with the
      spinal cord stimulator for pain control in a quadriplegic patient with central
      apnea due to complete spinal cord injury at the level of C2 from cervical
      epidural hematoma. After diaphragmatic pacing, the patient who was completely
      dependent on the mechanical ventilator could ambulate up to three hours every day
      without aid of mechanical ventilation during the 12 months of follow-up.
      Diaphragm pacing through unilateral phrenic nerve stimulation with spinal cord
      stimulator was feasible in an apneic patient with complete quadriplegia who was
      completely dependent on mechanical ventilation. Diaphragm pacing with the spinal
      cord stimulator is feasible and effective for the treatment of the central
      hypoventilation syndrome. 

PMID- 24294465
TI  - Split cord malformation combined with tethered cord syndrome in an adult.
AB  - Split cord malformations (SCMs) usually present in childhood, and are rarely
      reported in adults. And also, a cervicothoracic SCM associated with tethered cord
      syndrome has very rarely been reported in the literature. We report a case of SCM
      associated with tethered cord and spina bifida in an adult. This report describes
      the case of a 34-year-old woman who presented for evaluation of neck pain, back
      pain, and intermittent paraparesis of several months duration. The MRI and CT
      showed a SCM at the cervicothoracic level and a fibrous septum at the thoracic
      level. She underwent surgery for the SCM and tethered cord syndrome, and was
      followed for 7 years. Patient presented complete recovery in the follow-up. The
      authors discuss this unusual lesion and describe the anatomical relationship of
      the level of cord duplication and fibrous septum. 

PMID- 24294466
TI  - Surgical Tips to Preserve the Facet Joint during Microdiscectomy.
AB  - Lumbar microdiscectomy (MD) is the gold standard for treatment of lumbar disc
      herniation. Generally, the surgeon attempts to protect the facet joint in hopes
      of avoiding postoperative pain/instability and secondary degenerative
      arthropathy. We believe that preserving the facet joint is especially important
      in young patients, owing to their life expectancy and activity. However,
      preserving the facet joint is not easy during lumbar MD. We propose several
      technical tips (superolateral extension of conventional laminotomy, oblique
      drilling for laminotomy, and additional foraminotomy) for facet joint
      preservation during lumbar MD. 

PMID- 24294468
TI  - Pattern of chronic lung lesions in adults with sickle cell disease in Lagos,
      Nigeria.
AB  - BACKGROUND: The vascular response to recurrent tissue hypoxia and reperfusion
      following red blood cell sickling causes acute chest syndrome and chronic lung
      disease. The purpose of this study was to determine the pattern of chronic lung
      lesions and possible risk factors in sickle cell patients in lagos, Nigeria.
      METHODS: From July 2012 to April 2013, Pulmonary function test (PFT) and chest-x
      ray were determined in 56 eligible patients with sickle cell disease. Full blood
      count, red cell indices, hemoglobin F level, oxygen saturation, liver function
      tests, lactate dehydrogenase and tricuspid regurgitant jet velocity were
      measured. RESULTS: The mean age of the patients was 22+/-6 years. The mean forced
      vital capacity was low (76.49%+/-16). Abnormal PFTs were restrictive lung lesion
      (53%), obstructive lesions (3.7%) and mixed lesions (11%). The vital capacity had
      negative correlation with the white cell count and platelet count while it had
      positive correlation with age. There were no significant differences when normal
      and abnormal PFTs were compared based on the following laboratory data: lactate
      dehydrogenase (244 vs. 301), hematocrit (22.7 vs. 23.6), fetal hemoglobin (6.2%
      vs. 4.2%), mean corpuscular hemoglobin concentration (33.7 vs 33.3), aspartate
      transferase (34.2 vs. 35.1), tricuspid regurgitant jet velocity (1.3 vs. 0.92)
      and oxygen saturation (95.8 vs. 95.5). Abnormal x-ray findings were present in
      84% of participants. Chest x ray showed ischemic (17%), congestive (69%),
      fibrotic and inflammatory (14%) changes. CONCLUSION: Chronic lung lesion is
      common in sickle cell disease associated with rising white cell count, platelet
      count. All adult patients should have regular spirometry done to ensure early
      detection.

PMID- 24294467
TI  - Helicobacter pylori Infection in the general population: A Middle Eastern
      perspective.
AB  - Helicobacter pylori (H.pylori) infection is probably the most important factor
      that has been associated with the development of gastric cancers in human
      populations. However, there are no reliable data on the prevalence of this
      infection in the Middle East. In this article, based on a comprehensive
      literature review, we aimed to evaluate the situation in this region. The
      literature has been searched for the incidence and prevalence of H.pylori
      infection by Pubmed and Google Scholar. Search was repeated for each of the
      Middle Eastern countries, and to empower the method, citations of each found
      article were searched for the related studies. Seventy seven reports from the
      countries of the Middle East region had been reviewed and they all indicated a
      high rate of infection either in the general population or in the dyspeptic
      patients, the rate seemed to be higher in patients with dyspepsia, in patients
      with histologically confirmed gastritis and in patients of older age groups. 

PMID- 24294469
TI  - Association between diabetic retinopathy and hemoglobin level.
AB  - BACKGROUND: Anemia may be considered to be an independent risk factor for the
      development of diabetic retinopathy (DR) in patients with renal failure. The
      purpose of this study was to investigate the association between blood hemoglobin
      level and retinopathy in diabetic patients with normal renal function tests.
      METHODS: From 2009 to 2011, 1100 diabetic patients underwent retinal examination.
      Among them, 159 subjects were diagnosed to have DR and were compared with 318
      diabetic subjects with normal retinal examination as the control group. The level
      of hemoglobin (Hb), Hb A1C, serum iron, ferritin, and total iron binding capacity
      were compared between these two groups. RESULTS: Among the 159 patients with DR,
      112 (70.4%) had mild to moderate no proliferative retinopathy (NPDR) and 47
      (29.6%) had advanced retinopathy (severe NPDR or proliferative). The mean
      hemoglobin level in case and control group was 12.15+/-1.50 and 12.73+/-1.38
      g/dl, respectively (p<0.001). Anemia was seen in 45.9% and 26.1% in the case and
      the control groups, respectively (p<0.001). Ferritin <15ng/ml was seen in 7.4%
      and 6.1% of patients with and without DR, respectively (p=0.8). CONCLUSION: The
      results show that diabetic patients with retinopathy have lower level of
      hemoglobin and higher frequency of anemia. It is suggested that the level of
      hemoglobin should be evaluated periodically in diabetic patients.

PMID- 24294470
TI  - Hypoglycemic activity of Pyrus biossieriana Buhse leaf extract and arbutin:
      Inhibitory effects on alpha amylase and alpha glucosidase.
AB  - BACKGROUND: The mechanism of hypoglycemic and hypolipidemic activities of Pyrus
      biossieriana Buhse leaf extract (PbBLE) and its phytochemical component arbutin,
      have not been well determined. The present study was performed to understand the
      hypoglycemic activity mechanisms of pbBLE and arbutin more clearly. METHODS: In
      vitro enzymatic carbohydrate digestion with PbBLE and arbutin was assessed using
      alpha-amylase and alpha-glucosidase powders. The enzyme solutions were premixed
      with PbBLE and arbutin at different concentrations (0.1, 1, 10 and 100 mg/ml).
      Substrate solutions and colorimetric reagents were added to the reaction. The
      release of glucose was determined by spectrophotometric method. Acarbose was used
      as the positive control. RESULTS: The extract (10, 100 mg/ ml) completely inhibit
      alpha- amylase and alpha- glucosidase activities. The extract produced higher
      reduction of alpha-amylase and alpha-glucosidase activity than arbutin.
      Inhibition at various concentrations (0.1, 1, 10, 100 mg/ml) were significantly
      different (p<0.05). CONCLUSION: Our results exhibited that both the extract and
      arbutin were able to suppress the enzymes strongly.

PMID- 24294471
TI  - The association between CD166 detection rate and clinicopathologic parameters of
      patients with colorectal cancer.
AB  - BACKGROUND: Metastasis and recurrence of colorectal cancer after treatment is
      attributed to stem cells. The aim of this study was to determine the relationship
      between the expression of stem cell marker CD166 in colorectal cancer by
      immunohistochemistry and clinicopathologic parameters. METHODS: From 2006 to
      2012, 121 colectomy specimens of patients with colon cancer that were operated in
      Babol Medical University in Iran were evaluated. The paraffin blocks were
      extracted from the archive and the slides were prepared and stained for H&E and
      Immunohistochemical (IHC) methods. The samples with cytoplasmic and/or membranous
      staining more than 50% of tumor cells were considered as positive. Pathological
      parameter including type of tumor, stage and grade, vascular invasion and
      location of the tumors were recoerded. RESULTS: The mean age of the patients was
      58.7+/-15.1 years. Sixty-four (54.9%) patients were males. Eighty-six (71.1%)
      subjects were positive for cytoplasmic and 42 (34.7%) for membranous and 42
      (34.7%) for both cytoplasmic and membranous staining. The cytoplasmic expression
      of marker CD166 marker in mucinous type was 10 (50%) and was lower than non
      mucinous type 76 (75.2%) (p=0.031). There was significant relationship between
      membranous expression of CD166 marker and tumor location (right colon in
      23(54.8%), left colon in 18 (24.3%)] (p=0.001). There was no significant
      difference in the expression of marker with other demographic and
      clinicopathologic variables. CONCLUSION: The results show that CD166 expression
      was seen in more than two-thirds of the patients. The cytoplasmic expression of
      CD166 marker was higher in non-mucinous type. The distributions of membranous
      expression of marker CD166 was related more in right colon with colorectal
      cancer.

PMID- 24294472
TI  - Frequency of different oral lesions in children and adolescents in Babol,
      Northern Iran.
AB  - BACKGROUND: Few studies regarding oral lesions of children and adolescents were
      reported in the medical literature. The aim of this study was to determine the
      frequency of these lesions in patients from birth to 20 years old in Babol,
      Northern Iran. METHODS: The slides of all cases of oral lesions in children and
      adolescents, between 1990 and 2012 were obtained from the pathology archives of
      Shahid Beheshti Hospital and School of Dentistry, Babol University of Medical
      Sciences in Iran. The lesions were categorized as follows: cystic lesions,
      tumor/tumor-like lesions and inflammatory/reactive lesions. The data were
      collected and analyzed. RESULTS: The 244 retrieved cases accounted for 27% of
      total oral biopsies (8956) were performed during this period. Male to female
      ratio was 0.8. Inflammatory / reactive category (61.9%), tumor/ tumor-like
      category (23%) and cystic category (15.2%) were in order of frequency. Mucocele
      was seen in 55 (35.8%) of 151 cases of inflammatory/ reactive, centeral giant
      cell granoloma (CGCG) in 15 (26.8%) of 56 tumor/ tumor like and radicular cyst in
      14 (37.9%) of 37 cystic lesions. CONCLUSION: Our findings indicate that mucocele,
      CGCG and radicular cyst were frequent lesions in inflammatory / reactive, tumor /
      tumor like and cystic categories, respectively in our region.

PMID- 24294473
TI  - Chest radiological features among patients with smear positive pulmonary
      tuberculosis.
AB  - BACKGROUND: Chest x-ray has an important role in the diagnosis of tuberculosis
      (TB). The aim of this study was to determine the radiological changes in patients
      with smear positive pulmonary tuberculosis. METHODS: In this study, 325 patients
      with smear positive pulmonary TB was enrolled. The affected lobe or lobes of the
      left or right lung were recorded. The types of involvement were categorized based
      on patchy consolidation, cavitation, collapse consolidation and bronchopneumonia.
      The data were collected and analyzed. RESULTS: From the 325 patients, 116 (35.7%)
      were males and 209 (64.3%) were females. The most frequent involved site was the
      left upper lobe in 175 (53.8%) followed by the right upper lobe in 134 (41.2%)
      cases. The most frequent radiographic finding was bronchopneumonia in 242 (74.4%)
      cases. Patchy consolidation was detected in 99 (30.4%) patients. Cavitary lesion
      and pleural effusion were observed in 68 (20.9%) and 35 (10.7%) patients,
      respectively. CONCLUSION: The results show that pulmonary upper lobes were the
      most frequent involved sites.

PMID- 24294474
TI  - Comparative study on toxoplasma serology among HIV positive and HIV negative
      illicit drug users in Ahvaz, Iran.
AB  - BACKGROUND: Toxoplasmosis is a common parasitic infection in human around the
      world and can cause life-threatening encephalitis in human immunodeficiency virus
      (HIV) infected host. The aim of this study was to assess the frequency of
      toxoplasma infection in illicit drug users (IDUs) with and without HIV infection
      in Iran. METHODS: This study was carried out on 84 IDUs (42 HIV positive as case
      group and 42 HIV negative subjects as control group) from 2008 to 2009. Serum
      samples were tested for T. gondii IgG antibodies by Enzym linked immunosorbant
      assay (ELISA). Based on the company brochure kit, the test was defined positive
      if the antibody titer was 3 IU/ml or more. The data from these two groups were
      collected and analyzed. RESULTS: The mean age of HIV positive cases was 34.4+/
      8.6 and for HIV negative cases was 35.9+/-9.3 year. The mean age and distribution
      of sex in both groups were equal. The frequency of toxoplasma-IgG in HIV positive
      and HIV negative was 73.8% and 81%, respectively (p=0.19). CONCLUSION: The
      results show that prevalence of toxoplasmosis infection in the illicit drug users
      with HIV positive or negative is equal.

PMID- 24294475
TI  - Drug resistance pattern and associated risk factors of tuberculosis patients in
      the central province of Iran.
AB  - BACKGROUND: One of the fundamental issues of infectious disease treatment is drug
      resistance. The aim of the present study was to investigate the first-line anti
      tuberculosis drug resistance rates and determine the risk factors related to
      multidrug resistant mycobacterium tuberculosis. METHODS: From March 2011 to
      September 2012, mycobacterial strains were collected from one hundred fifteen
      diagnosed smear positive patients in the central province of Iran and tested for
      drug susceptible against ethambutol, rifampicin, isoniazid and streptomycin and
      the risk factors influencing the development of drug resistance were determined.
      RESULTS: The mean age of patients was 52.23+/-19.75 years. The rate of multi-drug
      resistant tuberculosis (MDR-TB) was 7.8%. Our study revealed that there were
      significant associations between prior treatment, age < 45 years, positive smear
      result at the end of the second month and positive smear result at the end of the
      third month. However, there was no association found between gender, inhabitant,
      nationality, close contact with TB patient, HIV infection and size of mantoux
      test. CONCLUSION: The results show that about 8% of TB cases in Arak are MDR TB.
      The age under 45 years, previous TB treatment and positive smear at the end of
      the second and third months of treatment were the main factors in the development
      of MDR-TB.

PMID- 24294476
TI  - Carcinoma of the breast presenting as deep vein thrombosis of the axillary vein.
AB  - BACKGROUND: Breast cancer is the most common type of malignancy in the female
      population, rarely is reported by thromboembolic events during the course of the
      disease. In this case, we present a rare case of breast cancer presenting as deep
      vein thrombosis of the axillary vein. CASE PRESENTATION: A 40-year- old female
      was admitted due to pain and swelling of her right arm and forearm of two months'
      duration. The right arm was grossly edematous with pitting edema. Breast
      examination showed non-tender fixed nodules in the right outer quadrant of the
      right breast. Doppler ultrasonography showed right axillary vein thrombosis. The
      pathologic examination of the nodules confirmed infiltrating ductal
      adenocarcinoma. CONCLUSION: This case highlights the procoagulant state of
      malignancies and it is important to remember that though rare, breast
      malignancies can present as deep venous thrombosis. This case also highlights the
      early and aggressive evaluation of any breast discharge to rule out carcinoma of
      the breast.

PMID- 24294477
TI  - Multiple recurrent vesicles in oral mucosa suggestive of superficial mucocele: An
      unusual presentation of allergic stomatitis.
AB  - BACKGROUND: Superficial mucocele presents as small, clear vesicle on noninflamed
      mucosa. In this study, we report several vesicles on the bucal mucosa of a woman
      diagnosed as superficial mucocele. CASE PRESENTATION: A 48-year old woman
      presented with multiple vesicles on her labial mucosa, ventral surface of the
      tongue, floor of the mouth and palate. A mucosal biopsy was taken from the
      vesicle. Histopathologically, intraepithelial mucocele was diagnosed. The lesion
      was successfully treated with mouthwash betamethasone. There has been no
      recurrence for 18 months. CONCLUSION: In the present study, several mucoceles
      were seen in the oral mucosa. No similar case was reported previously.

PMID- 24294478
TI  - Noninvasive evaluation of nonalcoholic steatohepatitis (NASH).

PMID- 24294479
TI  - Grip strength at four years in relation to birth weight.
AB  - Consistent positive relationships have been found between birth weight and grip
      strength in adults but evidence in children is limited. In a prospective general
      population birth cohort (Southampton Women's Survey) grip strength and
      anthropometry (height and weight) were measured in 968 children at age 4 years.
      Mean (standard deviation (S.D.)) birth weight was 3.48 (0.52) kg. Birth weight,
      adjusted for sex and gestational age, was positively associated with grip
      strength (beta = 0.22 kg/S.D. increase in adjusted birth weight; 95% CI 0.11,
      0.34). The relationship was attenuated after adjustment for current height and
      weight such that it became non-significant (beta = 0.03 kg/S.D. increase in
      adjusted birth weight; 95% CI -0.08, 0.14), suggesting that body size may be on
      the causal pathway. Early influences on muscle development appear to impact on
      grip strength in children as well as adults.

PMID- 24294481
TI  - Sachet drinking water in Ghana's Accra-Tema metropolitan area: past, present, and
      future.
AB  - Population growth in West Africa has outpaced local efforts to expand potable
      water services, and private sector sale of packaged drinking water has filled an
      important gap in household water security. Consumption of drinking water packaged
      in plastic sachets has soared in West Africa over the last decade, but the long
      term implications of these changing consumption patterns remain unclear and
      unstudied. This paper reviews recent shifts in drinking water, drawing upon data
      from the 2003 and 2008 Demographic and Health Surveys, and provides an overview
      of the history, economics, quality, and regulation of sachet water in Ghana's
      Accra-Tema Metropolitan Area. Given the pros and cons of sachet water, we suggest
      that a more holistic understanding of the drinking water landscape is necessary
      for municipal planning and sustainable drinking water provision.

PMID- 24294480
TI  - Photoredox Activation and Anion Binding Catalysis in the Dual Catalytic
      Enantioselective Synthesis of beta-Amino Esters.
AB  - The enantioselective oxidative C-H functionalization of tetrahydroisoquinoline
      derivatives is achieved through the merger of photoredox and asymmetric anion
      binding catalysis. This combination of two distinct catalysis concepts introduces
      a potentially general approach to asymmetric transformations in oxidative
      photocatalysis.

PMID- 24294482
TI  - Editorial.

PMID- 24294483
TI  - Study of effects of selective serotonin reuptake inhibitors on stages of sexual
      function in Iranian patients with major depressive disorder.
AB  - OBJECTIVE: Depression is one of the most common psychiatric disorders in the
      world. Lifetime prevalence is 15% among men and 25% among women. Selective
      serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and monoamine
      oxidase inhibitor antidepressants are often used for depression, with their own
      side effects. This study was carried out since little information on sexual
      dysfunction due to these medications is available in Iran. METHODS: This
      observational cross-sectional study included 100 patients attending a university
      or private psychiatry clinic who, after an interview based on Diagnostic and
      Statistical Manual of Mental Disorders fourth edition criteria, were considered
      depressed. These patients had no history of depression, sexual dysfunction or use
      of psychiatric medications. Sexual functioning of patients was evaluated at the
      start of the study, and after 2, 4 and 8 weeks of treatment. Data were evaluated
      using SPSS software and t and chi(2) tests. RESULTS: A total of 75% of patients
      reported sexual dysfunction: 66.7% of men and 79.7% of women. A total of 74.1% of
      patients on fluvoxamine, 100% on fluoxetine, 75% on sertraline, 71.4% on
      citalopram and 100% on paroxetine reported sexual dysfunction. The most frequent
      sexual dysfunction was difficulty with orgasm, which affected 41.17% of women and
      33.33% of men. CONCLUSION: The incidence of sexual dysfunction among users of
      SSRIs was highest in patients on fluvoxamine, but this was not statistically
      significant. Minimization of sexual side effects should be an essential
      consideration when prescribing antidepressants.

PMID- 24294484
TI  - A naturalistic comparison of the efficacy and safety of intramuscular olanzapine
      and intramuscular haloperidol in agitated elderly patients with schizophrenia.
AB  - OBJECTIVE: This study was a comparative investigation of the clinical efficacy
      and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated
      elderly patients with schizophrenia at 2 hours postdose. METHODS: The subjects
      were 23 inpatients who had been diagnosed with schizophrenia according to the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical
      symptoms were assessed using Positive and Negative Syndrome Scale Excited
      Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and
      their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS),
      Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale
      (DIEPSS) and laboratory tests. RESULTS: The mean reduction from baseline on the
      PANSS-EC total score, the PANSS total score and the ACES score were significantly
      greater in the IM olanzapine injection group than in the IM haloperidol injection
      group. The mean changes from baseline on the AIMS score, the BARS score and the
      DIEPSS total score were significantly better in the IM olanzapine injection group
      than in the IM haloperidol injection group. No serious adverse events such as
      paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive
      dyskinesia occurred between the two groups. CONCLUSION: The results of this study
      suggest the possibility that agitated elderly patients may result in superior
      efficacy and safety after IM olanzapine without serious adverse events in
      comparison with IM haloperidol.

PMID- 24294486
TI  - Prolonged hypothermia due to olanzapine in the setting of renal failure: a case
      report and review of the literature.
AB  - Temperature dysregulation is an infrequent but previously documented adverse
      effect of antipsychotic medications. The majority of documented cases involve
      durations of hypothermia of less than 24 h. We present the case of a patient on
      therapeutic olanzapine for bipolar disease with dehydration from gastroenteritis
      leading to acute kidney injury in the setting of stage III chronic kidney
      disease, who presented with severe hypothermia of 31.2 degrees C (88.2 degrees
      F). He required active rewarming in the intensive care unit for a total of 9
      days. This is the second case report of prolonged hypothermia from olanzapine in
      the setting of kidney disease. Clinicians should be aware that patients with
      renal dysfunction may be at increased risk for prolonged hypothermia from
      olanzapine. 

PMID- 24294485
TI  - A new logical insight and putative mechanism behind fluoxetine-induced
      amenorrhea, hyperprolactinemia and galactorrhea in a case series.
AB  - With the exception of fluoxetine, all selective serotonin reuptake inhibitors
      (SSRIs) commonly cause hyperprolactinemia through presynaptic mechanisms
      indirectly via 5-hydroxytryptamine (5-HT)-mediated inhibition of
      tuberoinfundibular dopaminergic neurons. However, there is little insight
      regarding the mechanisms by which fluoxetine causes hyperprolactinemia via the
      postsynaptic pathway. In this text, analysis of five spontaneously reported
      clinical cases of hyperprolactinemia resulting in overt symptoms of amenorrhea
      with or without galactorrhea, were scrupulously analyzed after meticulously
      correlating relevant literature and an attempt was made to explore the putative
      postsynaptic pathway of fluoxetine inducing hyperprolactinemia. Hypothetically,
      serotonin regulates prolactin release either by increasing oxytocin (OT) level
      via direct stimulation of vasoactitive intestinal protein (VIP) or indirectly
      through stimulation of GABAergic neurons. The pharmacodynamic exception and
      pharmacokinetic aspect of fluoxetine are highlighted to address the regulation of
      prolactin release via serotonergic pathway, either directly through stimulation
      of prolactin releasing factors (PRFs) VIP and OT via 5-HT2A receptors
      predominantly on PVN (neurosecretory magnocellular cell) or through induction of
      5-HT1A-mediated direct and indirect GABAergic actions. Prospective molecular and
      pharmacogenetic studies are warranted to visualize how fluoxetine regulate
      neuroendocrine system and cause adverse consequences, which in turn may explore
      new ways of approach of drug development by targeting the respective metabolic
      pathways to mitigate these adverse impacts. 

PMID- 24294487
TI  - Addition of amoxapine improves positive and negative symptoms in a patient with
      schizophrenia.

PMID- 24294489
TI  - Involving clients and their relatives and friends in psychiatric care: Case
      managers' experiences of training in resource group assertive community
      treatment.
AB  - The purpose of this project was to do a qualitative study of an integrated and
      flexible ACT model, the Resource Group Assertive Community Treatment (RACT), as
      seen from the perspective of case managers in training. The resource group
      normally consists of the client, the case manager and other available personnel
      in the medical and support areas, as well as family members. Nineteen theses were
      randomly chosen from a set of 80 theses written by a group of Swedish trainee
      case managers. The exams were conducted as case studies and concerned 19 clients
      with psychotic problems, 11 men and 8 women. "The Empirical Phenomenological
      Psychological Method" was used in the analysis, which generated five overarching
      themes: (a) the RACT program; (b) the resource group; (c) the empowerment of the
      client; (d) progress in treatment; and (e) the case manager. These together
      constituted a "therapeutic circle," in which methods and tools used within the
      RACT made it possible for the resource group to empower the clients who, as a
      result, experienced progress with treatment, during which the case manager was
      the unifying and connecting link.

PMID- 24294490
TI  - Measuring adult Attention Deficit Hyperactivity Disorder using the Quantified
      Behavior Test Plus.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) occurs in approximately 5% of the
      adult population and includes cardinal symptoms of hyperactivity, inattention,
      and impulsivity that may be difficult to identify with clinical routine methods.
      Continuous performance tests are objective measures of inattention and
      impulsivity that, combined with objective measures of motor activity, facilitate
      identification of ADHD among adults. The aim of the present study was to examine
      the sensitivity, specificity, and a composite measure of ADHD using objective
      measures of the ADHD-cardinal symptoms in adult participants with ADHD and non
      ADHD normative participants. Cardinal symptoms were measured in 55 participants
      having ADHD, 202 non-ADHD normative participants, as well as 84 ADHD normative
      participants using the Quantified Behavior Test Plus. This test measures
      inattention and impulsivity using a continuous performance test, and
      hyperactivity using a motion-tracking system. A predictive variable for the
      detection of ADHD called Prediction of ADHD yielded 86% sensitivity and 83%
      specificity. A composite measure of ADHD cardinal symptoms was developed using a
      Weighed Core Symptoms scale that indicated the total amount of ADHD symptoms on a
      numeric scale from 0 to 100. The total amount of ADHD symptoms was measured on a
      scale and predicted with the categorical variable in a majority of the cases in
      the present study. Further studies are needed in order to confirm the results
      with regard to additional clinical and normative samples. Careful consideration
      of potential sex and diagnostic subtype differences are noteworthy aspects for
      future examinations of the new instruments.

PMID- 24294491
TI  - Assessment of bone fragility with clinical imaging modalities.
AB  - INTRODUCTION: Osteoporotic fractures are a vital public health concern and have
      created a great economic burden to our society. Therefore, early diagnosis of
      patients with high risk of osteoporotic fractures is essential. The current gold
      standard for assessment of fracture risk is the measurement of bone mineral
      density using dual-energy X-ray absorptiometry. However, such techniques are not
      very effective in the diagnosis of patients with osteopaenia. Doctors are usually
      unable to make an informed decision regarding the treatment plan of these
      patients. In addition to bone mineral density, advanced imaging modalities have
      been explored in recent years to assess bone quality in other contributing
      factors, such as microarchitecture of trabecular bone, mineralisation,
      microdamage and bone remodelling rates. Currently, the microarchitecture of
      trabecular bone can be evaluated in vivo by high-resolution peripheral
      quantitative computed tomography techniques, which have a resolution of 80 um.
      However, such imaging techniques still remain a high-end research tool rather
      than a diagnostic tool for clinical applications. Thus, the limited accessibility
      and affordability of high-resolution peripheral quantitative computed tomography
      have become major concerns for the general public. Alternatively, combining bone
      mineral density measurements with stochastic assessments of spatial bone mineral
      density distribution from dual-energy X-ray absorptiometry images may offer an
      economic and efficient approach to non-invasively evaluate skeletal integrity and
      identify the at-risk population for osteoporotic fractures. The aim of this
      critical review is to assess bone fragility with clinical imaging modalities.
      CONCLUSION: High-resolution quantitative computed tomography imaging technique
      may provide direct measurements of microarchitectures of trabecular bone in vivo.
      However, it is an expensive method of imaging modality.

PMID- 24294492
TI  - Mechanisms underlying effects of 1,25-Dihydroxyvitamin D3 on the Th17 cells.
AB  - Th17 cells, a class of CD4(+) T cells, have been identified as novel effector
      cells, which play a pivotal role in several inflammatory and autoimmune diseases.
      1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has emerged
      as a direct regulator of immune system function in humans. Accumulating reports
      demonstrated that 1,25(OH)2D3 possessed anti-inflammatory activity on Th17 cells
      to maintain immunologic homeostasis. This report will review the novel immune
      regulatory role of 1,25(OH)2D3 in its potential use for Th17 cell-related
      inflammatory and autoimmune conditions. 

PMID- 24294494
TI  - Evaluation of Mycobacterium tuberculosis drug susceptibility in clinical
      specimens from Nigeria using genotype MTBDRplus and MTBDRsl assays.
AB  - The incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR)
      continues to increase alarmingly worldwide, and reliable and fast diagnosis of
      MDR is essential for the adequate treatment of patients. In contrast to the
      standard culture methods, nucleid acid amplification tests (NAATs) provide
      information about presence of Mycobacterium tuberculosis complex (MTBC) DNA and a
      potential resistance pattern within hours. We analyzed specimens of 110 patients
      from Nigeria comparing culture-based drug susceptibility testing (DST) to NAAT
      assays detecting isoniazid (INH), rifampicin (RMP) (GenoType MTBDRplus), and
      ethambutol (EMB) (GenoType MTBDRsl) resistance. Compared to DST, the GenoType
      MTBDRplus and MTBDRsl showed a specificity of 100% (86.3-100) and a sensitivity
      of 86% (42.1-99.6%) for detection of INH and a specificity of 100% (86.3-100) and
      a sensitivity of 83% (35.9-99.6%) for detection of RMP, and a sensitivity 100%
      (47.8-100%) for EMB resistance. However, in two strains, the NAAT assays provided
      false susceptible results as the mutations causing resistance were in genomic
      regions not covered by the probes of the GenoType MTBDRplus assay. We show that,
      in combination to DST, application of the GenoType MTBDRplus and GenoType MTBDRsl
      assays might be a useful additional tool to allow a rapid and safe diagnosis of
      MDR and extensively drug-resistant (XDR) MTBC. 

PMID- 24294493
TI  - Antemortem and postmortem examinations of the cattle calf naturally infected with
      Mycobacterium avium subsp. paratuberculosis.
AB  - A male cattle calf was detected as subclinically and naturally infected with
      Mycobacterium avium subspecies paratuberculosis (MAP) by a series of antemortem
      and postmortem tests. The MAP infection was identified by strong antibody and
      cell-mediated immune (CMI) response by a commercial ELISA kit and an intradermal
      Johnin test, respectively, in the initial antemortem examination. The antemortem
      status of the calf was further confirmed by MAP-specific interferon gamma (IFN
      gamma) response. For detection of IFN-gamma response, MAP-specific IFN-gamma
      release assays (IGRAs): (a) immuno capture ELISA (IC-ELISA) and (b) ELISPOT was
      employed. In addition, the presence of intracellular cytokine IFN-gamma was
      detected by flow cytometry. For all cytokine assays, MAP-specific recombinant
      antigens HSP65 and 35 kDa were employed to overcome the poor sensitivity and
      specificity resulting from the use of Johnin, the crude protein purified
      derivative of MAP. Postmortem examination of the MAP-infected/suspected cattle
      calf did not reveal any pathognomonic gross lesions in the gastro-intestinal
      tract. Histopathological examination of multiple organs showed the presence of
      epithelioid cells/macrophages and edematous lesions in the mesenteric lymph nodes
      suggestive of MAP; however, no granulomas were observed in the intestinal tract.
      The necropsy samples of rectum and mesenteric lymph nodes were positive for
      isolation of MAP by culture in the BACTECTM MGITTM 960 system, and acid fast
      bacilli were demonstrated by fluorescence microscopy confirming the infection.
      Due to differential and complex expression patterns of MAP antigens reported in
      literature, a combination of assays such as those based on IGRAs and antibody
      detection is essential. Therefore, the current experimental evidence confirms the
      efficacy of the approach adopted. However, further studies will be needed to
      understand the optimal combination MAP-specific antigens for use in IGRAs or
      antibody assays that can be used for detecting MAP infection in every stage of
      the disease. 

PMID- 24294495
TI  - Hookworm-related cutaneous larva migrans in patients living in an endemic
      community in Brazil: immunological patterns before and after ivermectin treatmen.
AB  - Hookworm-related cutaneous larva migrans (Hr-CLM) is caused by animal hookworm
      larvae migrating in the human epidermis where they elicit an inflammatory
      response. This study describes the immunological profile in Hr-CLM patients. In
      77 Hr-CLM patients from Manaus, Brazil, peripheral eosinophils were counted, and
      serum concentrations of total immunoglobulin E (IgE) and selected cytokines were
      determined by ELISA before and after treatment with ivermectin. Controls included
      patients' household members (endemic controls), non-endemic Brazilian and
      Japanese individuals. Eosinophil counts and total IgE in Hr-CLM patients were
      higher than in controls and correlated with disease severity. Concentrations of
      interleukin (IL)-4, IL-5, IL-6, and IL-10 were higher in Hr-CLM patients than in
      endemic controls (p < 0.001) while no differences were detected for interferon
      (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-1beta, IL-2, or transforming
      growth factor (TGF)-beta. Following ivermectin treatment, numbers of eosinophils
      and concentrations of IL-4, IL-5, and IL-10 decreased whereas IgE, IFN-gamma, and
      TGF-beta concentrations increased. The IL-5/IFN-gamma ratio declined from 5.9
      (interquartile range [IQR] 0.8-31.6) before to 0.1 (IQR 0.05-0.2; p = 0.001)
      after treatment. Thus, although an impact of other infections on the immune
      parameters determined cannot be excluded, Hr-CLM in endemic areas is associated
      with eosinophilia and elevated cytokine levels, particularly of IL-5 and IL-10,
      which decrease following ivermectin treatment. 

PMID- 24294496
TI  - Prevalence of plasmid-mediated AmpC beta-lactamases in Escherichia coli and
      Klebsiella pneumonia at tertiary care hospital of Islamabad, Pakistan.
AB  - Enterobacteriaceae produces AmpC beta-lactamases that make them resistant to
      commonly used antibiotics. AmpC beta-lactamases can be chromosomal-mediated or
      plasmid-mediated AmpC beta-lactamases (PABLs). The present study was undertaken
      to determine the occurrence of PABLs production in clinical isolates in
      Escherichia coli and Klebsiella pneumoniae. Among 1328 culture positive samples,
      511 isolates were identified as E. coli (81.02%, n = 414) and K. pneumonia
      (18.98%, n = 97). Cefoxitin resistance was observed in E. coli (19.57%, n = 81)
      and K. pneumoniae (22.68%, n = 22). Out of these cefoxitin resistant isolates,
      40.74% (n = 33) E. coli and 54.55% (n = 12) K. pneumoniae came out to be PABL
      producers. Prevalence of both PABLs and ESBLs in E. coli and K. pneumoniae was
      29.24% (n = 8) and 47% (n = 5), respectively. Isolates coproducing PABLs and ESBL
      exhibited increased minimum inhibitory concentrations (MICs) for selected
      cephalosporins. This study documented a high frequency of PABLs producing
      isolates from hospital which may lead to serious therapeutic problem. 

PMID- 24294497
TI  - Antibacterial activity of some medicinal plants against selected human pathogenic
      bacteria.
AB  - Medicinal plants are traditionally used for the treatment of human infections.
      The present study was undertaken to investigate Bergenia ciliata, Jasminum
      officinale, and Santalum album for their potential activity against human
      bacterial pathogens. B. ciliata, J. officinale, and S. album extracts were
      prepared in cold and hot water. The activity of plant extracts and selected
      antibiotics was evaluated against five bacterial pathogens including
      Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Pseudomonas
      aeruginosa, and Escherichia coli using agar well diffusion method. Among the
      three medicinal plants, B. ciliata extracts displayed potential activity against
      bacterial pathogens. Cold water extract of Bergenia ciliate showed the highest
      activity against B. subtilis, which is comparable with a zone of inhibition
      exhibited by ceftriaxone and erythromycin. J. officinale and S. album extracts
      demonstrated variable antibacterial activity. Further studies are needed to
      explore the novel antibacterial bioactive molecules. 

PMID- 24294498
TI  - Bacillus thuringiensis strain 199 can induce systemic resistance in tomato
      against Fusarium wilt.
AB  - The research work was performed to investigate the potential of Bacillus
      thuringiensis strain 199 to induce systemic resistance in tomato against Fusarium
      wilt. Roots of two-week-old seedlings of tomato plants were primed with bacterial
      strain. After 10 days of transplantation, some pots of tomato seedlings were
      provided with inoculum of Fusarium oxysporum lycopersici according to
      experimental design to induce disease. After 15 days of incubation period, plants
      challenged with F. oxysporum lycopersici alone were having obvious symptoms of
      Fusarium wilt. Plants that were treated with B. thuringiensis 199 + F. oxysporum
      lycopersici were having significant reduction of disease severity. Quantity of
      total phenolics increased 1.7-fold in bacterial-treated plants as compared to
      nontreated. Likewise, in case of defense-related enzymes, a significant increase
      of 1.3-, 1.8-, and 1.4-fold in polyphenol oxidase (PPO), phenyl ammonia lyase
      (PAL), and peroxidase (PO) was observed in comparison with untreated control.
      These results, hence, prove the potential of this bacterial strain for use as
      plant protection agent. 

PMID- 24294499
TI  - Efflux transport of serum amyloid P component at the blood-brain barrier.
AB  - Serum amyloid P component (SAP), a member of the innate immune system, does not
      penetrate the brain in physiological conditions; however, SAP is a stabilizing
      component of the amyloid plaques in neurodegenerative diseases. We investigated
      the cerebrovascular transport of human SAP in animal experiments and in culture
      blood-brain barrier (BBB) models. After intravenous injection, no SAP could be
      detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella
      typhimurium lipopolysaccharide injection increased BBB permeability for SAP and
      the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP
      in mice. Furthermore, when SAP was injected to the rat hippocampus, a time
      dependent decrease in brain concentration was seen demonstrating a rapid SAP
      efflux transport in vivo. A temperature-dependent bidirectional transport of FITC
      SAP was observed in rat brain endothelial monolayers. The permeability
      coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain
      to blood) than in the opposite direction. The luminal release of FITC-SAP from
      loaded endothelial cells was also significantly higher than the abluminal one.
      Our data indicate the presence of BBB efflux transport mechanisms protecting the
      brain from SAP penetration. Damaged BBB integrity due to pathological insults may
      increase brain SAP concentration contributing to development of neurodegenerative
      diseases. 

PMID- 24294500
TI  - Risk-taking and decision-making in youth: relationships to addiction
      vulnerability.
AB  - BACKGROUND: Decision-making and risk-taking behavior undergo developmental
      changes during adolescence. Disadvantageous decision-making and increased risk
      taking may lead to problematic behaviors such as substance use and abuse,
      pathological gambling and excessive internet use. METHODS: Based on MEDLINE
      searches, this article reviews the literature on decision-making and risk-taking
      and their relationship to addiction vulnerability in youth. RESULTS: Decision
      making and risk-taking behaviors involve brain areas that undergoing
      developmental changes during puberty and young adulthood. Individual differences
      and peer pressure also relate importantly to decision-making and risk-taking.
      CONCLUSIONS: Brain-based changes in emotional, motivational and cognitive
      processing may underlie risk-taking and decision-making propensities in
      adolescence, making this period a time of heightened vulnerability for engagement
      in additive behaviors.

PMID- 24294501
TI  - Problematic Internet Use, Mental Health and Impulse Control in an Online Survey
      of Adults.
AB  - BACKGROUND AND AIMS: Internet use has become a popular entertainment source and
      has become highly integrated into daily life. However, some people display
      problematic or addictive usage of the Internet. The present study attempts to
      fill current knowledge gaps regarding at-risk/problematic Internet use (ARPIU)
      and its relation to various health and functioning measures. METHODS: Online
      survey data from 755 adults in the United States were analyzed using chi-square
      and ANOVAs. RESULTS: The ARPIU group did not differ from the non-ARPIU group with
      respect to substance use. Individuals with ARPIU were, however, more likely to
      report at-risk/problematic engagement in video-game playing and gambling.
      Compared to the non-ARPIU group, the ARPIU group reported poorer self-control and
      higher levels of impulsivity and depression. CONCLUSIONS: ARPIU appears
      associated with other risk behaviors, particularly those that might be performed
      on the Internet. Future studies should examine the extent to which the Internet
      may promote engagement in these risk behaviors and the extent to which
      preventative interventions targeting better self-control or negative mood states
      might help a range of non-substance-related addictive behaviors.

PMID- 24294502
TI  - Serious Physical Fighting and Gambling-Related Attitudes and Behaviors in
      Adolescents.
AB  - BACKGROUND AND AIMS: Physical fighting and gambling are common risk behaviors
      among adolescents. Prior studies have found associations among these behaviors in
      adolescents but have not examined systematically the health and gambling
      correlates of problem-gambling severity amongst youth stratified by fight
      involvement. METHODS: Survey data were used from 2,276 Connecticut high-school
      adolescents regarding their physical fight involvement, gambling behaviors and
      perceptions, and health and functioning. Gambling perceptions and correlates of
      problem-gambling severity were examined in fighting and non-fighting adolescents.
      RESULTS: Gambling perceptions were more permissive and at-risk/problem gambling
      was more frequent amongst adolescents reporting serious fights versus those
      denying serious fights. A stronger relationship between problem-gambling severity
      and regular smoking was observed for adolescents involved in fights. DISCUSSION
      AND CONCLUSIONS: The more permissive gambling attitudes and heavier gambling
      associated with serious fights in high-school students suggest that youth who
      engage in physical fights warrant enhanced prevention efforts related to
      gambling. The stronger relationship between tobacco smoking and problem-gambling
      severity amongst youth engaging in serious fights suggest that fighting youth who
      smoke might warrant particular screening for gambling problems and subsequent
      interventions.

PMID- 24294503
TI  - Intensifying local radiotherapy for pancreatic cancer-who benefits and how do we
      select them?

PMID- 24294504
TI  - New possibilities and potential benefits for local control in locally recurrent
      pancreatic cancer.

PMID- 24294505
TI  - Re-irradiation with stereotactic body radiation therapy as a novel treatment
      option for isolated local recurrence of pancreatic cancer after multimodality
      therapy: experience from two institutions.
AB  - Limited treatment options exist for isolated local recurrence of pancreatic
      ductal adenocarcinoma (PDA) following surgical resection accompanied by
      neoadjuvant or adjuvant chemoradiation therapy (CRT). While select patients are
      eligible for re-resection, recurrent lesions are often unresectable. Stereotactic
      body radiation therapy (SBRT) represents a possible minimally invasive treatment
      option for these patients, although published data in this setting are currently
      lacking. This study examines the safety, efficacy, and palliative capacity of re
      irradiation with SBRT for isolated local PDA recurrence. All patients undergoing
      SBRT at two academic centers from 2008-2012 were retrospectively reviewed to
      identify those who received re-irradiation with SBRT for isolated local
      recurrence or progression of PDA after previous conventionally fractionated CRT.
      Information regarding demographics, clinicopathologic characteristics, therapies
      received, survival, symptom palliation, and toxicity was obtained from patient
      charts. Kaplan-Meier statistics were used to analyze survival and the log-rank
      test was used to compare survival among patient subgroups. Eighteen patients were
      identified. Fifteen had previously undergone resection with neoadjuvant or
      adjuvant CRT, while 3 received definitive CRT for locally advanced disease.
      Median CRT dose was 50.4 Gy [interquartile range (IQR), 45.0-50.4 Gy] in 28
      fractions. All patients subsequently received gemcitabine-based maintenance
      chemotherapy, but developed isolated local disease recurrence or progression
      without evidence of distant metastasis. Locally recurrent or progressive disease
      was treated with SBRT to a median dose of 25.0 Gy (range, 20.0-27.0 Gy) in 5
      fractions. Median survival from SBRT was 8.8 months (95% CI, 1.2-16.4 months).
      Despite having similar clinicopathologic disease characteristics, patients who
      experienced local progression greater than vs. less than 9 months after
      surgery/definitive CRT demonstrated superior median survival (11.3 vs. 3.4
      months; P=0.019) and progression-free survival (10.6 vs. 3.2 months; P=0.030)
      after SBRT. Rates of freedom from local progression at 6 and 12 months after SBRT
      were 78% (14 of 18 patients) and 62% (5 of 8 patients), respectively. Effective
      symptom palliation was achieved in 4 of 7 patients (57%) who reported symptoms of
      abdominal or back pain prior to SBRT. Five patients (28%) experienced grade 2
      acute toxicity; none experienced grade >=3 acute toxicity. One patient (6%)
      experienced grade 3 late toxicity in the form of small bowel obstruction. In
      conclusion, re-irradiation with hypofractionated SBRT in this salvage scenario
      appears to be a safe and reasonable option for palliation of isolated local PDA
      recurrence or progression following previous conventional CRT. Patients with a
      progression-free interval of greater than 9 months prior to isolated local
      recurrence or progression may be most suitable for re-irradiation with SBRT, as
      they appear to have a better prognosis with survival that is long enough for
      local control to be of potential benefit. 

PMID- 24294506
TI  - Preoperative chemoradiation and IOERT for unresectable or borderline resectable
      pancreas cancer.
AB  - BACKGROUND AND OBJECTIVES: Pre-operative chemoradiation (preop CRT) plus
      intraoperative electron irradiation (IOERT) has been used in the
      multidisciplinary treatment for patients with locally advanced unresectable or
      borderline resectable pancreas cancer. This review was performed to evaluate
      survival, relapse patterns and prognostic factors in patients treated with
      curative intent. METHODS: Between January 2002 and December 2010, 48 patients
      with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior
      to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative
      intent surgical resection. Resection status prior to preop CRT was locally
      unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45
      50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based
      regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11;
      R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also
      received adjuvant post-operative systemic chemotherapy. Outcomes evaluated
      include survival, local failure in the EBRT field (LF), central failure in the
      IOERT field (CF), and distant metastases. RESULTS: Resection status was
      predictive for survival and for patterns of relapse. For patients with at least a
      gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both
      median and overall survival were improved (median 23 vs. 10 months; 2-year, 40%
      vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented
      in 22/31 patients (71%); LF/CF in 5/26 (16%). CONCLUSIONS: Long term survival and
      disease control are achievable in select patients with borderline resectable or
      locally unresectable pancreas cancer when gross total surgical resection is
      achieved after preop CRT. Continued evaluation of curative-intent combined
      modality therapy is warranted in this high risk population, but additional
      strategies are needed to improve resectability and disease control.

PMID- 24294507
TI  - Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients
      with locally advanced unresectable pancreatic cancer.
AB  - PURPOSE: RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in
      patients with resectable pancreatic carcinoma following surgery. Our study aimed
      to investigate whether CA 19-9 provided similar prognostic information in
      patients with locally advanced unresectable pancreatic cancer (LAPC) treated with
      chemoradiotherapy (CRT) and to determine whether such endpoints should therefore
      be reported in future randomized trials. METHODS AND MATERIALS: Between December
      1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil
      based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only
      patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was
      evaluated were included in the analysis to avoid the confounding effect of
      hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9
      values available. The median age was 68 years and 52% were female. Categorized
      versions of the first post-CRT CA 19-9 were tested in 50 point increments
      beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using
      cut points of 10% increments from <0% (increased) to >90%. Survival was measured
      from the date of first post CRT CA 19-9 level until death or last follow-up.
      Univariate and multivariate statistical methodologies were used to determine
      significant prognostic factors for overall survival. RESULTS: Median CA 19-9
      prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT,
      patients with a decrease of >90% from their baseline CA 19-9 level had a
      significantly improved median survival than those that did not (16.2 vs. 7.5
      months, P=0.01). The median survival of patients with a CA 19-9 level lower than
      the median post CRT value was 10.3 months, compared with 7.1 months for those
      with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than
      50 U/mL and histologic grade I-II also showed prognostic significance (both
      P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of
      85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95%
      CI, 0.13-0.85, P=0.02). CONCLUSIONS: Our results indicate that post treatment CA
      19-9 is predictive for overall survival in patient with LAPC following CRT. We
      recommend that pre and post treatment CA 19-9 levels be obtained in patients
      receiving CRT and that these values be considered for prognostic nomograms and
      future clinical trials.

PMID- 24294508
TI  - Nab-paclitaxel monotherapy in refractory pancreatic adenocarcinoma.
AB  - BACKGROUND: The standard of care in patients with metastatic pancreatic
      adenocarcinoma is undefined beyond second line of treatment. There have been
      scant reports of benefit from nab-paclitaxel in patients with refractory
      pancreatic cancer. MATERIALS AND METHODS: A retrospective review was carried out
      in patients with pancreatic adenocarcinoma at Siteman Cancer Center, who had
      received nab-paclitaxel monotherapy after experiencing disease progression on
      standard treatments. Nab-paclitaxel was given either two out of every three weeks
      or three out of every four weeks. RESULTS: Twenty patients were identified and
      included for data analysis. Median age was 63.5 years old. All patients had
      previously received gemcitabine, while 40% had also received FOLFIRINOX. Median
      number of prior lines of systemic treatment was 2. Patients were treated for a
      median of 15 weeks, with a range of 1 to 41.7 weeks. Median dose of nab
      paclitaxel was 100 mg/m(2) with range of 75-125 mg/m(2). Best response imaging
      was available in 17 patients and 11 out of the 17 patients (64.7%) had stable
      disease. Median progression-free survival (PFS) was 3.7 months and overall
      survival (OS) were 5.2 months. Most common treatment related toxicities included
      grade 1 pneumonitis in five patients (25%), grade 3 or 4 neutropenia in three
      patients (15%), and dehydration resulting in hospitalization in one patient (5%).
      CONCLUSIONS: Nab-paclitaxel monotherapy had acceptable level of toxicity in a
      heavily pretreated patient population with pancreatic cancer and appeared to
      provide a clinical benefit. This agent is worthy of further prospective studies
      to evaluate extent of benefit after standard therapies have failed.

PMID- 24294509
TI  - Proton therapy may allow for comprehensive elective nodal coverage for patients
      receiving neoadjuvant radiotherapy for localized pancreatic head cancers.
AB  - BACKGROUND: Neoadjuvant radiotherapy has the potential to improve local disease
      control for patients with localized pancreatic cancers. Concern about an
      increased risk of surgical complications due to small bowel and gastric exposure,
      however, has limited enthusiasm for this approach. Dosimetric studies have
      demonstrated the potential for proton therapy to reduce intestinal exposure
      compared with X-ray-based therapy. We sought to determine if neoadjuvant proton
      therapy allowed for field expansions to cover high-risk nodal stations in
      addition to the primary tumor. METHODS: Twelve consecutive patients with
      nonmetastatic cancers of the pancreatic head underwent proton-based planning for
      neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic
      computed tomography (CT) scans with oral and intravenous contrast. Four
      dimensional planning scans were utilized to define an internal clinical target
      volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were
      generated to establish an initial PTV (PTV1). A second PTV was created using the
      initial PTV but was expanded to include the high-risk nodal targets as defined by
      the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both
      PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent
      (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney,
      left kidney and liver were recorded. Point spinal cord dose was limited to 45
      CGE. RESULTS: Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)).
      Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the
      substantial enlargement of the PTV when high-risk lymph nodes were included in
      the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and
      kidneys) were only minimally increased relative to the exposures seen when only
      the gross tumor target was treated. CONCLUSIONS: Proton therapy appears to allow
      for field expansions to cover high-risk lymph nodes without significantly
      increasing critical normal-tissue exposure in the neoadjuvant setting.

PMID- 24294510
TI  - Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant
      chemotherapy in esophageal cancer: phase II study.
AB  - PURPOSE: Concomitant use of chemotherapy and a radiation dose schedule that is
      more efficient compared to conventional radiotherapy may provide better outcomes
      in patients with esophageal cancer. This study aimed to assess the efficacy and
      tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated
      accelerated radiotherapy regimen in this group of patients. METHODS AND
      MATERIALS: A total of 20 newly diagnosed treatment-naive esophageal cancer
      patients were included in the study. Neoadjuvant cisplatin and 5-FU were given
      with 28-day intervals in a total of three courses. Along with the third course of
      chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with
      the following dose schedule: 5760 cGy/36 fr/16 day. RESULTS: All patients could
      receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade
      III acute toxicity (50%). None of the acute toxicity reactions required treatment
      discontinuation. Grade III or higher subacute/late toxicity occurred in 10
      patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients
      (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable
      disease, with only 1 patient (5%) having progressive disease. Seven patients
      underwent surgery. Overall, 8 patients (40%) had local control. The 5 years
      overall survival rate was 38.1%. CONCLUSIONS: Neoadjuvant hyperfractionated
      accelerated radiotherapy plus chemotherapy may help to target local disease
      control and increase survival in patients with esophageal cancer. Further studies
      to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted
      for maximum tumor control rates with minimal toxicity.

PMID- 24294511
TI  - Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal
      and hepatic metastases: a case-control study.
AB  - BACKGROUND: Concomitant treatment of colorectal peritoneal metastases (PM) and
      hepatic metastases (HM) remains controversial. This study compares the
      cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of
      colorectal peritoneal metastases (PM) with the CRS/IPC/hepatic resection
      treatment of colorectal PM and HM. METHODS: All patients from a prospective PM
      registry at the Uppsala institution treated concomitantly for PM/HM with
      CRS/IPC/hepatic resections were included in a PM/HM-group, n=11. They were
      matched 1(:)2 with patients from the registry being treated only for PM with
      CRS/IPC, n=22. Overall survival (OS), disease-free survival (DFS), morbidity,
      mortality, and recurrences were compared. RESULTS: The PM/HM-group had median OS
      of 15 months (95% CI: 6-46 months) and the PM-group had a median OS of 34 months
      (95% CI: 19-37 months), P=0.2. The DFS was 10 months (95% CI: 3-14 months) ?and
      24 months (95% CI: 10-32 months) respectively, P=0.1. Morbidity was 27% in both
      groups and one postoperative death in the PM/HM-group. Currently, 1/10 (10%)
      patients with an R1 resection are ?disease-free in the PM/HM group while 9/20
      (45%) are disease-free in the PM group (P=0.05). CONCLUSIONS: Concomitant
      treatment of PM and HM with CRS/IPC/hepatic resections is feasible with no
      significant increase in morbidity compared to CRS/IPC. The risk of recurrences is
      higher in the PM/HM group with a tendency towards worse DFS.

PMID- 24294512
TI  - Mismatch repair protein expression in colorectal cancer.
AB  - INTRODUCTION: Alterations in at least six of the genes that encode proteins
      involved in the mismatch repair (MMR) system have been identified in either HNPCC
      or sporadic colon cancer. We aimed to analyse the proportion of patients with
      colorectal cancer with loss of immunostaining for MMR proteins in order to
      determine the feasibility of molecular screening for the loss of MMR proteins
      through the study of unselected patients with colorectal cancer. METHODS: A group
      of 33 patients with colorectal cancer was randomly selected from the department
      of surgery bio-bank to determine the expression of MMR proteins in their FFPE
      tumour tissues using immunohistochemistry techniques. Changes in protein
      expression following transfection of colorectal tissues were observed in stained
      cells using Olympus BX60 microscope and image analySIS software. RESULTS: Of the
      tissue specimens in which acceptable immunostaining was achieved, three samples
      showed loss of one or more of the MMR proteins. Both hMLH1 and hPMS2 proteins
      were not expressed in a 36 years old woman with cancer of the caecum. The
      expression of hMSH6 protein was undetermined in tumour tissues retrieved from a
      61 years old man with cancer of the proximal colon. The third case was a 77 years
      old man with no documented family history of cancer, who had carcinoma of the
      rectum. He showed loss of hMLH1 expression in the tumour tissues. CONCLUSIONS:
      Our findings and the previous reports pointed out the importance of molecular
      screening of patients with colorectal cancer for MSI using immunohistochemistry.
      This strategy managed to identify mutations in patients otherwise would not have
      been detected.

PMID- 24294514
TI  - A case report of trastuzumab dose in gastric cancer.
AB  - INTRODUCTION: Trastuzumab (Herceptin(r), F. Hoffman-La Roche) is now approved for
      the treatment of metastatic HER2-positive gastric cancer based on the improved
      survival observed on the phase III Trastuzumab for Gastric Adenocarcinoma (ToGA)
      study. Standard dosing of trastuzumab is currently extrapolated from breast
      cancer data: a 3-week schedule (8 mg/kg load, 6 mg/kg q 3 weeks) or a weekly
      schedule (4 mg/kg load, 2 mg/kg q week). CASE STUDY: Our case study examines an
      HER2-positive metastatic gastric cancer patient that required a higher than
      currently recommended standard dose of trastuzumab to achieve treatment response.
      DISCUSSION: Several mechanisms may explain these findings and include higher
      clearance of trastuzumab, higher tumor burden, and pharmacologic resistance in
      metastatic gastric cancer versus breast cancer. The question of trastuzumab
      dosing in gastric cancer is currently being evaluated in a phase III clinical
      trial.

PMID- 24294515
TI  - Intrapancreatic accessory spleen presenting as a pancreatic mass.

PMID- 24294516
TI  - Metachronous pancreatic metastasis of an ovarian serous papillary adenocarcinoma
      after 8 years.

PMID- 24294517
TI  - Cholangiocarcinoma: treatment with sorafenib extended life expectancy to greater
      than four years.
AB  - INTRODUCTION: Cholangiocarcinomas arise from the epithelial cells of intrahepatic
      and extrahepatic bile ducts. They generally have a very poor prognosis. Many
      studies report a dismal median survival of approximately 6 months. In this case,
      we have a patient diagnosed with cholangiocarcinoma who has remarkably exceeded
      life expectancy to greater than 4 years with a fourth line agent Sorafenib. CASE
      DESCRIPTION: This is a 51 y/o male who was diagnosed with cholangiocarcinoma
      approximately ?4.5 years ago. After initial work up suggested locally advanced
      carcinoma, the patient was started on systemic chemotherapy. Despite multiple
      cycles with GEMOX, capecitabine and 5-FU, the carcinoma progressed. A fourth line
      agent, Sorafenib, was initiated. This multikinase inhibitor drug is FDA approved
      for hepatocellular carcinoma and renal cell carcinoma, however the potential
      efficacy of this agent for treating cholangiocarcinoma is largely unknown.
      Despite some latest trials suggesting a median survival of ?4.4 months, our
      patient has survived on this chemotherapy agent for almost 4 years now.
      DISCUSSION: This case illustrates the potential benefit of using Sorafenib in
      locally advanced cholangiocarcinoma. This provides hope for more trials, to
      establish selection criteria for administration of this drug.

PMID- 24294513
TI  - Diet and supplements and their impact on colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is the third commonest cancer and the third leading
      cause of cancer death among men and women. It has been proposed that dietary
      factors are responsible for 70-90% of colorectal cancer and diet optimization may
      prevent most cases. AIM: To evaluate the role of dietary components and
      supplements in colorectal cancer. METHODS: Bibliographical searches were
      performed in Pubmed for the terms "diet and colorectal cancer", "diet and colon
      cancer", "diet and rectal cancer", "nutrition and colorectal cancer", "probiotics
      and colorectal cancer", "prebiotics and colorectal cancer", "alcohol and cancer"
      and "colorectal cancer epidemiology". RESULTS: Consumption of processed or red
      meat, especially when cooked at high temperatures may be associated with
      increased risk of colorectal cancer. The evidence for dietary fibre is unclear
      but foods that contain high amounts of fibre are usually rich in polyphenols
      which have been shown to alter molecular processes that can encourage colorectal
      carcinogenesis. Meta-analyses provide evidence on the benefits of circulating,
      diet-derived and supplemented, vitamin D and Calcium. We also found that diets
      rich in Folate may prevent colorectal carcinoma. The evidence on dietary
      micronutrients such as Zinc and Selenium in association with colorectal cancer is
      not conclusive. It has been suggested that there may be a direct association
      between alcohol intake and colorectal cancer. In vitro and in vivo studies have
      highlighted a possible protective role of prebiotics and probiotics. CONCLUSIONS:
      The lack of randomized trials and the presence of confounding factors including
      smoking, physical activity, obesity and diabetes may often yield inconclusive
      results. Carefully designed randomized trials are recommended.

PMID- 24294518
TI  - RE: Takatori K, Terashima K, Yoshida R, Horai A, Satake S, Ose T, Kitajima N,
      Kinoshita Y, Demizu Y, Fuwa N. Upper gastrointestinal complications associated
      with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer.
      J Gastroenterol. 2013; (E-pub only).

PMID- 24294520
TI  - Pediatric multiple sclerosis: current concepts and consensus definitions.
AB  - Multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central
      nervous system (CNS) commonly diagnosed in adults, is being recognized
      increasingly in children. An estimated 1.7%-5.6% of all patients with MS have
      clinical symptoms before reaching the age of 18 years. In comparison with adults,
      the diagnosis of MS in children can be more difficult, being dismissed or
      misdiagnosed as other clinical disorders. Although adults and children share
      basic aspects of the disorder, children have distinctive clinical features,
      neuroimaging, laboratory, and courses of the disease. The 2010 McDonald criteria
      have simplified the requirements for establishing the diagnosis of MS and have
      been proposed to be applicable for the diagnosis of pediatric MS, mainly in
      children 12 years and older. This paper describes the distinctive features of
      common pediatric demyelinating disorders, including MS, and summarizes the most
      recent advances based on the available literature. 

PMID- 24294519
TI  - NEUROBIOLOGICAL ASPECTS OF SUICIDE AND SUICIDE ATTEMPTS IN BIPOLAR DISORDER.
AB  - Suicide and bipolar disorder (BD) are challenging, complex, and intertwined areas
      of study in contemporary psychiatry. Indeed, BD is associated with the highest
      lifetime risk for suicide attempt and completion of all the psychiatric
      conditions. Given that several clinical risk factors for both suicide and BD have
      been well noted in the literature, exploring the neurobiological aspects of
      suicide in BD may provide insights into both preventive measures and future novel
      treatments. This review synthesizes findings regarding the neurobiological
      aspects of suicide and, when applicable, their link to BD. Neurochemical
      findings, genes/epigenetics, and potential molecular targets for current or
      future treatments are discussed. The role of endophenotypes and related proximal
      and distal risk factors underlying suicidal behavior are also explored. Lastly,
      we discuss the manner in which preclinical work on aggression and impulsivity may
      provide additional insights for the future development of novel treatments.

PMID- 24294523
TI  - Chelation therapy with oral solution of deferiprone in transfusional iron
      overloaded children with hemoglobinopathies.
AB  - Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic
      hemolysis, and increased iron absorption and leads to tissue injury requiring the
      early use of chelating agents. The available agents are parenteral deferoxamine
      and oral deferiprone and deferasirox. There are limited data on the safety and
      efficacy of deferiprone at a very young age. The aim of our study was the
      presentation of data regarding the use of oral solution of deferiprone in 9
      children (mean age 6.5, range 2-10) with transfusion dependent hemoglobinopathies
      (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta
      thalassemia). The mean duration of treatment was 21.5 months (range 15-31). All
      children received the oral solution without any problems of compliance. Adverse
      reactions were temporary abdominal discomfort and diarrhea (1 child), mild
      neutropenia (1 child) that resolved with no need of discontinuation of treatment,
      and transient arthralgia (1 child) that resolved spontaneously. The mean ferritin
      levels were significantly reduced at the end of 12 months (initial 2440 versus
      final 1420  MU g/L, P < 0.001). This small study shows that oral solution of
      deferiprone was well tolerated by young children and its use was not associated
      with major safety concerns. Furthermore, it was effective in decreasing serum
      ferritin. 

PMID- 24294521
TI  - An update in the use of antibodies to treat glioblastoma multiforme.
AB  - Glioblastoma is a deadly brain disease and modest improvement in survival has
      been made. At initial diagnosis, treatment consists of maximum safe surgical
      resection, followed by temozolomide and chemoirradiation or adjuvant temozolomide
      alone. However, these treatments do not improve the prognosis and survival of
      patients. New treatment strategies are being sought according to the biology of
      tumors. The epidermal growth factor receptor has been considered as the hallmark
      in glioma tumors; thereby, some antibodies have been designed to bind to this
      receptor and block the downstream signaling pathways. Also, it is known that
      vascularization plays an important role in supplying new vessels to the tumor;
      therefore, new therapy has been guided to inhibit angiogenic growth factors in
      order to limit tumor growth. An innovative strategy in the treatment of glial
      tumors is the use of toxins produced by bacteria, which may be coupled to
      specific carrier-ligands and used for tumoral targeting. These carrier-ligands
      provide tumor-selective properties by the recognition of a cell-surface receptor
      on the tumor cells and promote their binding of the toxin-carrier complex prior
      to entry into the cell. Here, we reviewed some strategies to improve the
      management and treatment of glioblastoma and focused on the use of antibodies. 

PMID- 24294524
TI  - The superficial musculoaponeurotic system of the face: a model explored.
AB  - Regional differences in the integument of the body are explained, at least in
      part, by differences in fascial arrangements. In the face, where the skin is more
      mobile due to the action of the underlying facial muscles, fascial organisation
      is important for support and separation of muscle groups. This study used
      bequeathed cadaver material to investigate a current model of the SMAS proposed
      by Macchi et al., the original boundaries of which were explored and extended
      using both histology and gross dissection. As a clearly identifiable structure
      spanning the lateral and midface, the SMAS in the specimen supported the model
      proposed by Macchi et al. The three main findings that support the model were the
      layered morphological appearance of the SMAS, its progression from fibrous to
      aponeurotic in a lateral to medial direction, and the enveloping of the
      zygomaticus musculature. Extension beyond the proposed model into the temporal
      region was observed, but nasal and forehead regions showed no evidence of SMAS,
      while its presence in the cervical platysma region remained inconclusive. Fascial
      and soft tissue variability was considerable within facial regions of the
      examined specimen, helping to explain the debate around the SMAS in the
      literature. 

PMID- 24294522
TI  - Cardiovascular disease in latin american patients with systemic lupus
      erythematosus: a cross-sectional study and a systematic review.
AB  - Objective. This study was performed to determine the prevalence of and associated
      risk factors for cardiovascular disease (CVD) in Latin American (LA) patients
      with systemic lupus erythematosus (SLE). Methods. First, a cross-sectional
      analytical study was conducted in 310 Colombian patients with SLE in whom CVD was
      assessed. Associated factors were examined by multivariate regression analyses.
      Second, a systematic review of the literature on CVD in SLE in LA was performed.
      Results. There were 133 (36.5%) Colombian SLE patients with CVD. Dyslipidemia,
      smoking, coffee consumption, and pleural effusion were positively associated with
      CVD. An independent effect of coffee consumption and cigarette on CVD was found
      regardless of gender and duration of disease. In the systematic review, 60
      articles fulfilling the eligibility criteria were included. A wide range of CVD
      prevalence was found (4%-79.5%). Several studies reported ancestry, genetic
      factors, and polyautoimmunity as novel risk factors for such a condition.
      Conclusions. A high rate of CVD is observed in LA patients with SLE. Awareness of
      the observed risk factors should encourage preventive population strategies for
      CVD in patients with SLE aimed at facilitating the suppression of cigarette
      smoking and coffee consumption as well as at the tight control of dyslipidemia
      and other modifiable risk factors. 

PMID- 24294525
TI  - Similar adverse pregnancy outcome in native and nonnative dutch women with
      pregestational type 2 diabetes: a multicentre retrospective study.
AB  - Objective. To assess the incidence of adverse pregnancy outcome in native and
      nonnative Dutch women with pregestational type 2 diabetes (T2D) in a multicenter
      study in The Netherlands. Methods. Maternal characteristics and pregnancy outcome
      were retrospectively reviewed and the influence of ethnicity on outcome was
      evaluated using independent t-test, Mann-Whitney U-test, and chi-square test.
      Results. 272 pregnant women (80 native and 192 non-native Dutch) with
      pregestational T2D were included. Overall outcome was unfavourable, with a
      perinatal mortality of 4.8%, major congenital malformations of 6.3%, preeclampsia
      of 11%, preterm birth of 19%, birth weight >90th percentile of 32%, and a
      Caesarean section rate of 42%. In nonnative Dutch women, the glycemic control was
      slightly poorer and the gestational age at booking somewhat later as compared to
      native Dutch women. However, there were no differences in incidence of
      preeclampsia/HELLP, preterm birth, perinatal mortality, macrosomia, and
      congenital malformations between those two groups. Conclusions. A high incidence
      of adverse pregnancy outcomes was found in women with pregestational T2D,
      although the outcome was comparable between native and non-native Dutch women.
      This suggests that easy access to and adequate participation in the local health
      care systems contribute to these comparable outcomes, offsetting potential
      disadvantages in the non-native group. 

PMID- 24294526
TI  - Therapeutic effects of tai chi in patients with Parkinson's disease.
AB  - Objective. The purpose of the study was to investigate the effects of a 12-week
      program of therapeutic Tai Chi on the motor function and physical function of
      idiopathic Parkinson's disease patients (PDs). Methods. The participants were 22
      clinically stable PDs in Hoehn-Yahr stages 1-2 randomly assigned to a therapeutic
      Tai Chi group (TTC, N = 11) or a control group (CON, N = 9). Two subjects in
      control group did not complete the study for personal reasons. TTC was performed
      three days a week (60 min/session). Motor symptoms by the UPDRS were assessed,
      and tests of physical function were administered before and after the 12-week
      trial. Results. The TTC group, as compared to the CON group, showed changes in
      the mentation, behavior, mood, and motor scales of the UPDRS (P < 0.05, P < 0.01,
      resp.), with no significant main effects on the activities of daily living scale
      (ADL). However, there was a significant interaction between the time and
      intervention group on ADL (P < 0.05). There were no significant main effects for
      any of the physical function variables. There were significant interaction
      effects in balance and agility (P < 0.05, resp.). Conclusions. This study showed
      that TTC training had modest positive effects on the functional status of
      Parkinson's disease patients. 

PMID- 24294528
TI  - Prostatic carcinosarcoma with lung metastases.
AB  - Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term
      prognosis. The cancer is typically discovered at an advanced stage, and with less
      than 100 reported cases, there is limited literature concerning treatment
      options. Our patient presented with a history of benign prostatic hypertrophy,
      erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the
      patient had prostatic adenocarcinoma, but histopathology after prostatectomy
      revealed carcinosarcoma. It has been over six years since this patient's
      diagnosis of carcinosarcoma. Over this span of time, he has received a radical
      prostatectomy, radiotherapy, and androgen ablative therapy. The patient also
      developed multiple lung metastases that have been treated with video-assisted
      thoracic surgery and stereotactic body radiosurgery. Overall, he has remained
      unimpaired and in good condition despite his aggressive form of cancer. 

PMID- 24294529
TI  - Gastric adenocarcinoma with yolk sac tumor differentiation and liver metastasis
      of yolk sac tumor component.
AB  - Gastric adenocarcinoma with yolk sac tumor (YST) differentiation has rarely been
      reported. We report a case of primary gastric adenocarcinoma with yolk sac tumor
      differentiation and liver metastases of the YST component in a 50-years-old
      patient. This was suspected due to high serum level of alpha fetoprotein in the
      presence of a gastric fundal tumor. Gastric carcinoma with yolk sac tumor
      component is a rare entity with a poor prognostic outcome. 

PMID- 24294530
TI  - Primary neuroendocrine carcinoma of ocular adnexa.
AB  - We present our findings in a case of primary neuroendocrine carcinoma (NEC) of
      the lacrimal gland and a case of primary Merkel cell carcinoma (MCC) of the
      eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three
      months earlier. We performed excision biopsy and histopathological examination
      indicated that he had a primary NEC of the left lacrimal gland. He underwent
      chemotherapy followed by excision including the clinically visible margins and 50
      Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis
      for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in
      the right upper eyelid and was referred to our hospital because the size was
      increasing rapidly. A complete surgical excision of the margins of the tumor was
      performed with histopathological confirmation of negative margins. The final
      diagnosis was a primary MCC of the right upper eyelid. After surgery, he
      underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or
      metastasis was found for two years. Although primary NEC of the ocular adnexa is
      extremely rare, the tumor has high malignancy and readily metastasizes. Thus,
      combined therapy including surgery, radiotherapy, and/or chemotherapy is needed
      for complete management of NEC. 

PMID- 24294531
TI  - Idiopathic Calcinosis Cutis over Elbow in a 12-Year Old Child.
AB  - Calcinosis cutis is an uncommon disorder caused by an abnormal deposit of calcium
      phosphate in the skin in various parts of the body. Four main types of calcinosis
      cutis have been recognized according to etiology: associated with localized or
      widespread tissue changes or damage (dystrophic calcification), that associated
      with an abnormal calcium and phosphorus metabolism (metastatic calcification),
      not associated with any tissue damage or demonstrable metabolic disorder
      (idiopathic calcification), and Iatrogenic. Very few cases of idiopathic
      calcinosis cutis are reported in early childhood in the literature. We report one
      such case of idiopathic calcinosis cutis over elbow in a 12-year-old female
      child. Histological examinations of the lesions resected in this case reveal
      calcium deposits in the dermis, surrounded by foreign body giant cells.
      Idiopathic calcinosis cutis is a rare phenomenon and occurs in the absence of
      known tissue injury or systemic metabolic defect. It is important to delineate it
      from other calcification disorders for further plan of management. Medical
      therapy in calcinosis cutis is of limited benefit in pediatric age group and
      poses a challenging problem of postsurgical management. 

PMID- 24294527
TI  - Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras
      Isoforms and Wild-Type versus Mutated Proteins.
AB  - The ability to selectively and directly target activated Ras would provide
      immense utility for treatment of the numerous cancers that are driven by
      oncogenic Ras mutations. Patients with disorders driven by overactivated wild
      type Ras proteins, such as type 1 neurofibromatosis, might also benefit from
      progress made in that context. Activated Ras is an extremely challenging direct
      drug target due to the inherent difficulties in disrupting the protein:protein
      interactions that underlie its activation and function. Major investments have
      been made to target Ras through indirect routes. Inhibition of farnesyl
      transferase to block Ras maturation has failed in large clinical trials. Likely
      reasons for this disappointing outcome include the significant and
      underappreciated differences in the isoforms of Ras. It is still plausible that
      inhibition of farnesyl transferase will prove effective for disease that is
      driven by activated H-Ras. The principal current focus of drugs entering clinic
      trial is inhibition of pathways downstream of activated Ras, for example,
      trametinib, a first-in-class MEK inhibitor. The complexity of signaling that is
      driven by activated Ras indicates that effective inhibition of oncogenic
      transduction through this approach will be difficult, with resistance being
      likely to emerge through switch to parallel pathways. Durable disease responses
      will probably require combinatorial block of several downstream targets. 

PMID- 24294532
TI  - Spontaneous symptomatic pseudoarthrosis at the l2-l3 intervertebral space with
      diffuse idiopathic skeletal hyperostosis: a case report.
AB  - Pseudoarthrosis at the intervertebral space in patients with ankylosing
      spondylitis has occasionally been reported, but symptomatic pseudoarthrosis at
      the intervertebral disc level is rare in patients with diffuse idiopathic
      skeletal hyperostosis (DISH). Here, we report a case of symptomatic
      pseudoarthrosis at the L2-L3 intervertebral space that was diagnosed based on
      clinical history. We first performed L1-L5 fixation, but back-out of the pedicle
      screw occurred in the early postoperative phase and may have been caused by a
      short fixation range and concomitant Parkinson's disease. However, the prognosis
      of the case was favorable after a second surgery. This case indicates that a
      fixation range of at least 3 above and 3 below is necessary for bone fracture of
      a thoracolumbar vertebra and pseudoarthrosis in patients with DISH. 

PMID- 24294533
TI  - The use of percutaneous lumbar fixation screws for bilateral pedicle fractures
      with an associated dislocation of a lumbar disc prosthesis.
AB  - Study Design. Case report. Objective. To identify a safe technique for salvage
      surgery following complications of total disc replacement. Summary of Background
      Data. Lumbar total disc replacement (TDR) is considered by some as the gold
      standard for discogenic back pain. Revision techniques for TDR and their
      complications are in their infancy. This case describes a successful method of
      fixation for this complex presentation. Methods and Results. A 48-year-old male
      with lumbar degenerative disc disease and no comorbidities. Approximately two
      weeks postoperatively for a TDR, the patient represented with acute severe back
      pain and the TDR polyethylene inlay was identified as dislocated anteriorly.
      Subsequent revision surgery failed immediately as the polyethylene inlay
      redislocated intraoperatively. Further radiology identified bilateral pedicle
      fractures, previously unseen on the plain films. The salvage fusion of L5/S1
      reutilized the anterior approach with an interbody fusion cage and bone graft.
      The patient was then turned intraoperatively and redraped. The percutaneous
      pedicle screws were used to fix L5 to the sacral body via the paracoccygeal
      corridor. Conclusion. The robust locking screw in the percutaneous screw allowed
      a complete fixation of the pedicle fractures. At 3-year followup, the patient has
      an excellent result and has returned to playing golf. 

PMID- 24294534
TI  - Severe hemorrhage from the umbilical cord at birth: a preventable cause of
      neonatal shock.
AB  - Posthemorrhagic anemia is a rare but important cause of anemia in neonates,
      second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia
      are reported from fetomaternal hemorrhage or umbilical cord accidents in utero.
      This case report describes a preterm infant who developed severe anemia and shock
      immediately after delivery related to an acute hemorrhage through patent
      umbilical cord vessels secondary to a tear in the umbilical cord at the site of
      cord clamping. We believe that umbilical cord bleeding from errors in cord
      clamping could be an important cause of acute blood loss in the delivery room and
      that it may result in significant clinical morbidity, especially in extremely
      premature infants. 

PMID- 24294535
TI  - An unusual case of dual left anterior descending artery with coronary computed
      tomographic angiographic correlation.
AB  - Dual left anterior descending artery (LAD) is a rare coronary anomaly that is
      important to recognize at coronary imaging as it may influence reperfusion
      strategies. Four types of dual LAD are described by the traditional literature.
      We present a novel case of dual LAD with coronary computed tomographic
      angiographic correlation that does not fit into this classification system.
      Rather, our case supports the recently proposed notion of adding a fifth variant
      to the traditional dual LAD classification system. 

PMID- 24294536
TI  - A review of the inflammatory chorioretinopathies: the white dot syndromes.
AB  - The white dot syndromes are a group of inflammatory chorioretinopathies of
      unknown etiology which have in common a unique and characteristic appearance of
      multiple yellow-white lesions affecting multiple layers of the retina, retinal
      pigment epithelium (RPE), choriocapillaris, and the choroid. They also have
      overlapping clinical features. We discuss acute retinal pigment epitheliopathy,
      multiple evanescent white dot syndrome, acute posterior multifocal placoid
      pigment epitheliopathy, multifocal choroiditis and panuveitis, acute zonal occult
      outer retinopathy, birdshot chorioretinopathy, and serpiginous choroidopathy.
      Some of these diseases are associated with a viral prodrome suggesting a possible
      viral/infectious etiology, while others are associated with a number of systemic
      processes suggesting an autoimmune etiology. We also review the presentation,
      evaluation/diagnosis, and treatment of these entities as well as the prognosis.
      Where applicable we discuss recent advancements in diagnosing and treating the
      white dot syndromes. 

PMID- 24294537
TI  - Bioprospecting the Bibleome: Adding Evidence to Support the Inflammatory Basis of
      Cancer.
AB  - BACKGROUND CANCER SIGNIFICANCE AND QUESTION: BioProspecting is a novel approach
      that enabled our team to mine genetic marker related data from the New England
      Journal of Medicine (NEJM) utilizing Systematized Nomenclature of Medicine
      Clinical Terms (SNOMED CT) and the Human Gene Ontology (HUGO). Genes associated
      with disorders using the Multi-threaded Clinical Vocabulary Server (MCVS) Natural
      Language Processing (NLP) engine, whose output was represented as an ontology
      network incorporating the semantic encodings of the literature. Metabolic
      functions were used to identify potentially novel relationships between (genes or
      proteins) and (diseases or drugs). In an effort to identify genes important to
      transformation of normal tissue into a malignancy, we went on to identify the
      genes linked to multiple cancers and then mapped those genes to metabolic and
      signaling pathways. FINDINGS: Ten Genes were related to 30 or more cancers, 72
      genes were related to 20 or more cancers and 191 genes were related to 10 or more
      cancers. The three pathways most often associated with the top 200 novel cancer
      markers were the Acute Phase Response Signaling, the Glucocorticoid Receptor
      Signaling and the Hepatic Fibrosis/Hepatic Stellate Cell Activation pathway.
      MEANING AND IMPLICATIONS OF THE ADVANCE: This association highlights the role of
      inflammation in the induction and perhaps transformation of mortal cells into
      cancers. MAJOR FINDINGS: BioProspecting can speed our identification and
      understanding of synergies between articles in the biomedical literature. In this
      case we found considerable synergy between the Oncology literature and the Sepsis
      literature. By mapping these associations to known metabolic, regulatory and
      signaling pathways we were able to identify further evidence for the inflammatory
      basis of cancer.

PMID- 24294538
TI  - A Frailty-Model-Based Method for Estimating Age-Dependent Penetrance from Family
      Data.
AB  - Accurate estimates of disease risk (penetrance) associated with inherited gene
      mutations are critical for the clinical management of individuals at risk, but
      this estimation raises many statistical challenges especially when performed in a
      family-based design. In this paper, we propose a general frailty model-based
      approach to accommodate this design, where the frailty random effect accounts for
      shared risk among family members not due to the observed risk factors. It is of
      major interest when the goal is to discover other genetic variations besides the
      major gene and to get accurate estimates of penetrance (i.e. unbiased by unknown
      confounding factors). This approach is further extended to accommodate missing
      genotypes in family members and the non-random ascertainment of the families.
      Simulation results show that the proposed method performs well in realistic
      settings. Finally, a family-based breast cancer study of the BRCA1 and BRCA2
      genes is used to illustrate the method.

PMID- 24294539
TI  - Coronary Arteries in Childhood Heart Disease: Implications for Management of
      Young Adults.
AB  - Survival of patients with congenital heart defects has improved dramatically.
      Many will undergo interventional catheter or surgical procedures later in life.
      Others will develop atherosclerotic or post-surgical coronary heart disease. The
      coronary artery anatomy in patients with congenital heart disease differs
      substantially from that seen in the structurally normal heart. This has
      implications for diagnostic procedures as well as interventions. The unique
      epicardial course seen in some defects could impair interpretation of coronary
      angiograms. Interventional procedures, especially at the base of the heart, risk
      injuring unusually placed coronary arteries so that coronary artery anatomy must
      be delineated thoroughly prior to the procedure. In this review, we will describe
      the variants of coronary artery anatomy and their implications for interventional
      and surgical treatment and for sudden death during late follow-up in several
      types of congenital heart defects including: tetralogy of Fallot, truncus
      arteriosus, transposition of the great arteries, double outlet right ventricle,
      congenitally corrected transposition of the great arteries and defects with
      functionally one ventricle. We will also discuss the coronary abnormalities seen
      in Kawasaki disease.

PMID- 24294542
TI  - Impaired of a non-DNA dependent methylation status decides the fat decision of
      bone marrow-derived C3H10T1/2 stem cell.
AB  - A decrease in the lineage commitment of multipotent Mesenchymal stem cells (MSC)
      to the bone forming osteoblast lineage and an increase in the commitment to the
      fat forming adipocyte lineage is more common in bone marrow of elderly persons. A
      link between methylation status and MSC differentiation remains unclear.
      Therefore, we hypothesize that hypomethylation may decide the fate decisions of
      MSC. In the current study, murine bone marrow derived-C3H10T1/2 stem cell was
      used to examine the role of methylation mechanism on the differentiation
      potential of stem cells into osteoblasts or adipocytes. C3H10T1/2 cells were
      treated with Periodate oxidized adenosine (Adox), an inhibitor of S
      adenosylhomocysteine-dependent hydrolase (SAHH), which in turn block the non-DNA
      methylation pathway. The effect of hypomethylation on C3H10T1/2 stem cell
      differentiation was determined by measuring the alkaline phosphates activity and
      the degree of mineralization as well as Oil-red O staining and lipid content. The
      ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) was
      determined as a metabolic indicator of cellular methylation potential. It was
      clearly observed that hypomethylation significantly (P < 0.05) reduces SAM: SAH
      ratio, alkaline phosphates activity, calcification and thereby, osteoblast
      differentiation. Conversely, adipocyte differentiation was stimulated by
      hypomethylation. Altogether, our data suggest that non-DNA hypomethylation
      changes the differentiation potential of C3H10T1/2 stem cells for less osteogenic
      and more adipogenic. 

PMID- 24294540
TI  - Congenital Heart Defects in Adults : A Field Guide for Cardiologists.
AB  - Advances in cardiology and cardiac surgery allow a large proportion of patients
      with congenital heart defects to survive into adulthood. These patients
      frequently develop complications characteristic of the defect or its treatment.
      Consequently, adult cardiologists participating in the care of these patients
      need a working knowledge of the more common defects. Occasionally, patients with
      congenital heart defects such as atrial septal defect, Ebstein anomaly or
      physiologically corrected transposition of the great arteries present for the
      first time in adulthood. More often patients previously treated in pediatric
      cardiology centers have transitioned to adult congenital heart disease centers
      for ongoing care. Some of the more important defects in this category are
      tetralogy of Fallot, transposition of the great arteries, functionally single
      ventricle defects, and coarctation. Through this field guide, we provide an
      overview of the anatomy of selected defects commonly seen in an adult congenital
      practice using pathology specimens and clinical imaging studies. In addition, we
      describe the physiology, clinical presentation to the adult cardiologist,
      possible complications, treatment options, and outcomes.

PMID- 24294543
TI  - A biomechanical study of spherical grip.
AB  - Use of the hand is vital in working life due to the grabbing and pinching it
      performs. Spherical grip is the most commonly used, due to similarity to the
      gripping of a computer mouse. Knowledge of its execution and the involved
      elements is essential. Analysis of this exertion with surface electromyography
      devices (to register muscular activity) and accelerometer devices (to register
      movement values ) can provide multiple variables. Six subjects performed ball
      gripping and registered real-time electromyography (thenar region, hypothenar
      region, first dorsal interosseous, flexors of the wrist, flexor carpi ulnaris and
      extensors of the wrist muscles) and accelerometer (thumb, index, middle, ring,
      pinky and palm) values. The obtained data was resampled "R software" and
      processed "Matlab Script" based on an automatic numerical sequence recognition
      program. Electromyography values were normalized on the basis of maximum
      voluntary contraction, whilst modular values were calculated for the acceleration
      vector. After processing and analysing the obtained data and signal, it was
      possible to identify five stages of movement in accordance with the module vector
      from the palm. The statistical analysis of the variables was descriptive: average
      and standard deviations. The outcome variables focus on the variations of the
      modules of the vector (between the maximum and minimum values of each module and
      phase) and the maximum values of the standardized electromyography of each
      muscle. Analysis of movement through accelerometer and electromyography variables
      can give us an insight into the operation of spherical grip. The protocol and
      treatment data can be used as a system to complement existing assessments in the
      hand. 

PMID- 24294541
TI  - Suicide Gene Therapy for Cancer - Current Strategies.
AB  - Current cancer treatments may create profound iatrogenic outcomes. The adverse
      effects of these treatments still remain, as the serious problems that practicing
      physicians have to cope with in clinical practice. Although, non-specific
      cytotoxic agents constitute an effective treatment modality against cancer cells,
      they also tend to kill normal, quickly dividing cells. On the other hand,
      therapies targeting the genome of the tumors are both under investigation, and
      some others are already streamlined to clinical practice. Several approaches have
      been investigated in order to find a treatment targeting the cancer cells, while
      not affecting the normal cells. Suicide gene therapy is a therapeutic strategy,
      in which cell suicide inducing transgenes are introduced into cancer cells. The
      two major suicide gene therapeutic strategies currently pursued are: cytosine
      deaminase/5-fluorocytosine and the herpes simplex virus/ganciclovir. The novel
      strategies include silencing gene expression, expression of intracellular
      antibodies blocking cells' vital pathways, and transgenic expression of caspases
      and DNases. We analyze various elements of cancer cells' suicide inducing
      strategies including: targets, vectors, and mechanisms. These strategies have
      been extensively investigated in various types of cancers, while exploring
      multiple delivery routes including viruses, non-viral vectors, liposomes,
      nanoparticles, and stem cells. We discuss various stages of streamlining of the
      suicide gene therapy into clinical oncology as applied to different types of
      cancer. Moreover, suicide gene therapy is in the center of attention as a
      strategy preventing cancer from developing in patients participating in the
      clinical trials of regenerative medicine. In oncology, these clinical trials are
      aimed at regenerating, with the aid of stem cells, of the patients' organs
      damaged by pathologic and/or iatrogenic factors. However, the stem cells carry
      the risk of neoplasmic transformation. We discuss cell suicide inducing
      strategies aimed at preventing stem cell-originated cancerogenesis.

PMID- 24294544
TI  - Application of alizarin colorimetric measurements for quantification of amine
      extraction by model food simulants from epoxy polymer.
AB  - A simple and straightforward method has been proposed for quantification of
      residual amine in cured epoxy resin. Non-bounded triethylenetetramine was
      extracted from epoxy polymer and determined via spectrophotometry using alizarin
      chromophore. Four solvents commonly used as food simulants, namely water, 95%
      ethanol, 10% ethanol and 3% acetic acid were examined. Released amine induces
      changes in the absorption spectrum of alizarin, by decreasing the intensity of
      the maximum at 430 nm band and mutually increasing the 527 nm band. These changes
      were proportional to the amounts of amine concentration in samples. The
      statistical significance of obtained calibration curves was validated. Among
      studied solvents, the highest amine release was observed for water solution and
      3% acetic acid, that is approximately 7% w/w. The maximal amount of residual
      amine extracted with 95% ethanol was about 1.25%, while for 10% ethanol this
      amount was 2%. The effect of aging of the samples and exposure to artificial
      sunlight were also examined. The proposed method has been proven to be fast, low
      cost and directly applicable for analysis of typical epoxy resins. 

PMID- 24294545
TI  - Proposed design for the PGAA facility at the TRIGA IPR-R1 research reactor.
AB  - BACKGROUND: This work presents an initial proposed design of a Prompt Gamma
      Activation Analysis (PGAA) facility to be installed at the TRIGA IPR-R1, a 60
      years old research reactor of the Centre of Development of Nuclear Technology
      (CDTN) in Brazil. The basic characteristics of the facility and the results of
      the neutron flux are presented and discussed. FINDINGS: The proposed design is
      based on a quasi vertical tube as a neutron guide from the reactor core, inside
      the reactor pool, 6 m below the room's level where shall be located the rack
      containing the set sample/detector/shielding. The evaluation of the thermal and
      epithermal neutron flux in the sample position was done considering the
      experimental data obtained from a vertical neutron guide, already existent in the
      reactor, and the simulated model for the facility. METHODS: The experimental
      determination of the neutron flux was obtained through the standard procedure of
      using Au monitors in different positions of the vertical tube. In order to
      validate both, this experiment and calculations of the simulated model, the flux
      was also determined in different positions in the core used for sample
      irradiation. The model of the system was developed using the Monte Carlo code
      MCNP5. CONCLUSION: The preliminary results suggest the possibility of obtaining a
      beam with minimum thermal flux of magnitude 10(6) cm(-2) s(-1), which confirm the
      technical feasibility of the installation of PGAA at the TRIGA IPR-R1 reactor.
      This beam would open new possibilities for enhancing the applications using the
      reactor.

PMID- 24294546
TI  - Nutrient utilization and rumen metabolism in sheep fed Prosopis juliflora pods
      and Cenchrus grass.
AB  - The present study was conducted to evaluate the effect of replacement of Prosopis
      juliflora pods (PJP) in the concentrate mixture fed to sheep along with Cenchrus
      grass (CG). Twenty four adult Malpura rams (3-5 years, 45.4 +/- 4.26 kg) were
      randomly divided into three equal groups on the basis of age and live weight
      (LW). Mature green Prosopis juliflora pods were collected, dried and ground to
      replace concentrate mixture at 0 (G1), 30% (G2) or 40% (G3). Cenchrus grass was
      offered ad libitum whereas the concentrate mixture was fed at the rate of 1% LW.
      Nutrient digestibility did not differ among the groups while N balance data
      showed reduced utilization in G3. However, the animals in G1, G2 and G3
      maintained LW and their nutritional profile indicated surplus of energy and
      protein with comparable feed value of all the three diets. Rumen pH decreased and
      volatile fatty acids increased (P < 0.05) 4 h after feeding in G2 and G3 compared
      to G1. In summary, Prosopis juliflora pods can replace concentrate mixture up to
      40% in sheep feeding without any adverse effect on nutrient intake and
      utilization as well as rumen fermentation characteristics. 

PMID- 24294547
TI  - Efficacy of retroperitoneal laparoscopic ureterolithotomy for the treatment of
      large proximal ureteric stones and its impact on renal function.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of
      retroperitoneal laparoscopic ureterolithotomy for the management of large
      proximal ureteric stones and the impact of this treatment on postoperative renal
      function. METHODS: The data of 12 patients (7 men and 5 women; mean age, 68.5 +/-
      8.9 years) with large pyeloureteral junction (2 cases) and upper ureteral (10
      cases) stones (25.3 +/- 7.4 mm) that had undergone retroperitoneal laparoscopic
      ureterolithotomy were reviewed. Renal function was analyzed by the estimated
      glomerular filtration rate (eGFR) and renal scintigraphy using 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) before and 3 months after surgery. RESULTS:
      The mean operative time was 129.5 +/- 21.4 minutes, with a mean blood loss of
      64.4 +/- 78.2 mL. The mean duration of hospital stay after surgery was 6.4 +/-
      2.7 days, and the mean duration of stenting was 7.2 +/- 1.7 weeks. A stone
      clearance rate of 100% was achieved, and no patient developed ureteric stricture.
      99mTc-MAG3 scintigraphy showed that laparoscopic removal of calculi did not
      affect renal function, but did improve ureteral occlusion. CONCLUSIONS:
      Retroperitoneal laparoscopic ureterolithotomy is a safe and effective treatment
      option for reducing ureteral obstruction in select patients with large proximal
      ureteric stones.

PMID- 24294548
TI  - Biomedical named entity extraction: some issues of corpus compatibilities.
AB  - BACKGROUND: Named Entity (NE) extraction is one of the most fundamental and
      important tasks in biomedical information extraction. It involves identification
      of certain entities from text and their classification into some predefined
      categories. In the biomedical community, there is yet no general consensus
      regarding named entity (NE) annotation; thus, it is very difficult to compare the
      existing systems due to corpus incompatibilities. Due to this problem we can not
      also exploit the advantages of using different corpora together. In our present
      work we address the issues of corpus compatibilities, and use a single objective
      optimization (SOO) based classifier ensemble technique that uses the search
      capability of genetic algorithm (GA) for NE extraction in biomedicine. We
      hypothesize that the reliability of predictions of each classifier differs among
      the various output classes. We use Conditional Random Field (CRF) and Support
      Vector Machine (SVM) frameworks to build a number of models depending upon the
      various representations of the set of features and/or feature templates. It is to
      be noted that we tried to extract the features without using any deep domain
      knowledge and/or resources. RESULTS: In order to assess the challenges of corpus
      compatibilities, we experiment with the different benchmark datasets and their
      various combinations. Comparison results with the existing approaches prove the
      efficacy of the used technique. GA based ensemble achieves around 2% performance
      improvements over the individual classifiers. Degradation in performance on the
      integrated corpus clearly shows the difficulties of the task. CONCLUSIONS: In
      summary, our used ensemble based approach attains the state-of-the-art
      performance levels for entity extraction in three different kinds of biomedical
      datasets. The possible reasons behind the better performance in our used approach
      are the (i). use of variety and rich features as described in Subsection
      "Features for named entity extraction"; (ii) use of GA based classifier ensemble
      technique to combine the outputs of multiple classifiers.

PMID- 24294549
TI  - Technical tips and procedural steps in endovascular aortic aneurysm repair with
      concomitant recanalization of iliac artery occlusions.
AB  - PURPOSE: The goal of this paper is to describe our technical strategy and
      procedural steps for endovascular aneurysm repair (EVAR) when performed with
      concomitant recanalization of the iliac artery occlusion. MATERIALS AND METHODS:
      Three octogenarians having abdominal aortic aneurysm (AAA)/common iliac artery
      aneurysms (CIAA) with unilateral external iliac artery (EIA) occlusion underwent
      EVAR with recanalization of the occluded iliac arteries. Crossing the iliac
      artery occlusions was attempted in a retrograde approach using a 0.035 inch
      hydrophilic guidewire. After passage of a guidewire, predilation was performed
      using 6mm balloon. Then a 12-Fr sheath was advanced via the occluded EIA for
      contralateral iliac limb delivery. Internal iliac artery embolization was
      subsequently performed as needed. A self-expanding stent was then placed in the
      occluded EIA after EVAR. RESULTS: Recanalization of the EIA occlusion, followed
      by stentgraft delivery through the occlusion and EVAR, was successfully performed
      in all three patients. Penetration of the occluded EIA was successfully achieved
      only by retrograde approach in two patients, and by bidirectional approach in the
      other patient. No perioperative complication or death occurred. Postoperative CT
      showed no type I or III endoleaks in the aneurysms and patent iliac arteries in
      all patients. CONCLUSIONS: Total endovascular repairs were successfully performed
      for three patients with AAA and concomitant unilateral EIA occlusions. The
      proposed steps described in this report might reduce the complication rate and
      enhance the technical success rate associated with this procedure.

PMID- 24294550
TI  - Experimental system for measurement of radiologists' performance by visual search
      task.
AB  - PURPOSE: Detective performance of radiologists for "obvious" targets should be
      evaluated by visual search task instead of ROC analysis, but visual task have not
      been applied to radiology studies. The aim of this study was to set up an
      environment that allows visual search task in radiology, to evaluate its
      feasibility, and to preliminarily investigate the effect of career on the
      performance. MATERIALS AND METHODS: In a darkroom, ten radiologists were asked to
      answer the type of lesion by pressing buttons, when images without lesions, with
      bulla, ground-glass nodule, and solid nodule were randomly presented on a
      display. Differences in accuracy and reaction times depending on board
      certification were investigated. RESULTS: The visual search task was successfully
      and feasibly performed. Radiologists were found to have high sensitivity,
      specificity, positive predictive values and negative predictive values in non
      board and board groups. Reaction time was under 1 second for all target types in
      both groups. Board radiologists were significantly faster in answering for bulla,
      but there were no significant differences for other targets and values.
      CONCLUSION: We developed an experimental system that allows visual search
      experiment in radiology. Reaction time for detection of bulla was shortened with
      experience.

PMID- 24294551
TI  - The value of resident presentations at scientific meetings.

PMID- 24294552
TI  - Characteristics and management of superior semicircular canal dehiscence.
AB  - Objectives To review the characteristic symptoms of superior semicircular canal
      dehiscence, testing and imaging of the disease, and the current treatment and
      surgical options. Results and Conclusions Symptoms of superior semicircular canal
      dehiscence (SSCD) include autophony, inner ear conductive hearing loss, Hennebert
      sign, and sound-induced episodic vertigo and disequilibrium (Tullio phenomenon),
      among others. Potential etiologies noted for canal dehiscence include possible
      developmental abnormalities, congenital defects, chronic otitis media with
      cholesteatoma, fibrous dysplasia, and high-riding jugular bulb. Computed
      tomography (CT), vestibular evoked myogenic potentials, Valsalva maneuvers, and
      certain auditory testing may prove useful in the detection and evaluation of
      dehiscence syndrome. Multislice temporal bone CT examinations are normally
      performed with fine-cut (0.5- to 0.6-mm) collimation reformatted to the plane of
      the superior canal such that images are parallel and orthogonal to the plane. For
      the successful alleviation of auditory and vestibular symptoms, a bony dehiscence
      can be surgically resurfaced, plugged, or capped through a middle fossa
      craniotomy or the transmastoid approach. SSCD should only be surgically treated
      in patients who exhibit clinical manifestations. 

PMID- 24294553
TI  - Skull base involvement by acinic cell carcinoma of the parotid gland.
AB  - Objective Describe the clinical course and outcomes of patients with primary
      acinic cell carcinoma (ACC) of the parotid gland with skull base invasion or
      metastasis. Design Retrospective case series (1995-2011) at a single institution.
      Results Ten patients met study criteria. Mean and median time from initial
      diagnosis of parotid ACC to development of skull base disease were 14.6 and 10.2
      years, respectively. Two patients demonstrated skull base disease on initial
      presentation. Those who pursued further treatment after developing disease at the
      skull base underwent surgery (4/7), stereotactic radiosurgery (4/7), or external
      beam radiation (3/7). The 10-year Kaplan-Meier estimated overall survival after
      initial diagnosis of parotid ACC was 80%. Once skull base invasion occurred, 2
      year estimated overall survival was 50%. Conclusion Although primary ACC of the
      parotid generally caries an excellent prognosis, tumor control with cranial base
      disease is difficult and the majority of patients present with late aggressive
      recurrences. Our observations underscore the importance of long-term follow-up in
      this patient group. 

PMID- 24294554
TI  - Endoscopic surgery of skull base chordomas.
AB  - Objective To assess our clinical experience in treating midline intracranial
      pathology using minimally invasive surgical techniques. Design Retrospective
      chart review of patients undergoing endoscopic endonasal resection of clival
      chordomas. Setting Two tertiary referral centers in Australia and New Zealand.
      Main Outcome Measures Patients were assessed by intraoperative findings
      (macroscopic resection rate, tumor size, and operative complications) and
      clinical outcomes (residual disease, postoperative complications, recurrence
      rate, and mortality). Results Fourteen patients underwent endoscopic resection of
      clival chordomas (seven primary, seven revision) with a mean follow-up of 41.45
      months (3 to 104 months). Macroscopic resection rates were 71% and 29%,
      respectively. Mean operative time was 386 minutes. Overall cerebrospinal fluid
      (CSF) leak rate was 3/14 (21%) and, using the nasoseptal flap, it was 0/5 (0%).
      Two patients developed late recurrence; one died of disease and one was treated
      with intensity modulated radiation therapy. Overall mortality was 2/14 (14%).
      Conclusion Endoscopic resection of clival chordomas is a safe and viable
      alternative to the traditional open approach. The nasoseptal flap is an excellent
      method of obtaining a watertight skull base closure. Furthermore, this series
      highlighted the fact that the primary attempt at surgery offers the best chance
      to achieve a total resection. 

PMID- 24294555
TI  - Combined subgaleal/myocutaneous technique for temporalis muscle dissection.
AB  - Background The frontal branch of the facial nerve (FBFN) is the most susceptible
      neural structure to injury during frontotemporal craniotomies. The balance
      between adequate temporalis muscle mobilization and frontal branch protection
      with minimal anatomical alteration is the philosophy behind our approach to
      temporalis muscle dissection. Objective To describe a combined
      subgaleal/myocutaneous technique for dissection and mobilization of the
      temporalis muscle in anterolateral cranial approaches. Methods Interdisciplinary
      literature review of the anatomical course of the FBFN was performed.
      Retrospective analysis of anterolateral craniotomies performed at our institution
      in which the combined subgaleal/myocutaneous (CSGMC) technique was performed.
      Results A total of 71 cases of anterolateral craniotomies (excluding full variant
      orbitozygomatic) were performed with the successful application of a CSGMC
      technique (36 pterional, 31 orbitopterional, and 4 fronto-orbital). Partial
      frontalis weakness was transient in one case. Conclusion The CSGMC technique
      provides sufficient protection for the FBFN and allows for adequate mobilization
      for a variety of skull base exposures while minimally violating myofascial
      anatomy. This is the first reported technique that allows both adequate
      temporalis muscle mobilization with performance of the one-piece orbitofrontal
      and orbitopterional approaches, without disruption of the superficial/deep
      temporalis fascia and fat-pad complex. 

PMID- 24294556
TI  - Transorbital neuroendoscopic management of sinogenic complications involving the
      frontal sinus, orbit, and anterior cranial fossa.
AB  - Transnasal endoscopic surgery has remained at the forefront of surgical
      management of sinogenic complications involving the frontal sinus, orbit, and
      anterior skull base. However, the difficulty in accessing certain areas of these
      anatomical regions can potentially limit its use. Transorbital neuroendoscopic
      surgery (TONES) was recently introduced to transgress the limits of transnasal
      endoscopic surgery; the access that it provides could add additional surgical
      pathways for treating sinogenic complications involving the frontal sinus, orbit,
      and anterior cranial fossa. We describe a prospective series of 13 patients who
      underwent TONES for the management of various sinogenic complications, including
      epidural abscess, orbital abscess, and fronto-orbital mucocele or mucopyocele, as
      well as subperiosteal abscess presenting with orbital apex syndrome. The primary
      outcome measurement was the efficacy of TONES in treating these pathologies.
      TONES provided effective access to the frontal sinus, orbit, and the anterior
      cranial fossa. All patients demonstrated postoperative resolution of initial
      clinical symptoms with well-hidden surgical scars. There were no ophthalmologic
      complications or recurrence of pathology. Based on our experience, TONES appears
      to provide a valuable addition to the current surgical armamentarium for treating
      selected complications of sinusitis. 

PMID- 24294557
TI  - The association of meningitis with postoperative cerebrospinal fluid fistula.
AB  - Objective To determine the risk factors for and the clinical course of
      postoperative meningitis following lateral skull base surgery and to determine
      its relationship to cerebrospinal fluid (CSF) fistula. Patients Patients
      undergoing lateral skull base surgery between July 1999 and February 2010 at an
      academic tertiary referral center. All subjects had culture-proven meningitis or
      suspected bacterial meningitis in the postoperative period. Medical records were
      compared with the lateral skull base patients who did not develop meningitis.
      Results Of 508 procedures, 16 patients developed meningitis (3.1%). The most
      common diagnosis was acoustic neuroma in 81.3%; 68.8% of patients had a CSF leak
      prior to onset of meningitis, and 50% received a lumbar drain. The median time
      from surgery to the onset of meningitis was 12 days with a range of 2 to 880
      days. The relative risk of developing meningitis in the setting of postoperative
      CSF fistula is 10.2 (p < 0.0001). No meningitis-associated mortality was
      observed. Conclusions Postoperative meningitis occurred in a small number of
      patients undergoing lateral skull base surgery. A postoperative CSF fistula leads
      to an increased risk of meningitis by a factor of 10.2. 

PMID- 24294558
TI  - Endoscopic endonasal pituitary surgery: impact of surgical education on operation
      length and patient morbidity.
AB  - Objectives To determine the difference in operative times and associated
      complications for cases performed solely by attending-level surgeons versus cases
      assisted by surgeons-in-training for endoscopic endonasal pituitary surgeries.
      Design Retrospective chart review. Setting Tertiary-care academic medical center.
      Participants A total of 228 patients having undergone endoscopic endonasal
      pituitary surgery from 2005 to 2011. Main Outcome Measure Duration of surgery
      comparing attending only (AO) and trainee-assisted (TA) surgeries. Results Thirty
      seven (19%) of 198 cases were identified as AO surgeries, the remaining 161 (81%)
      were TA. Operative times (minutes) for the AO group were significantly shorter
      than the TA group (149.1 +/- 54.8 vs 219.5 +/- 83.7, p < 0.001). The AO group had
      fewer intraoperative cerebrospinal fluid leaks (30% vs 39%, p = 0.318), decreased
      estimated blood loss (408 mL vs 523 mL, p = 0.176), fewer postoperative
      complications (27% vs 37%, p = 0.268), and shorter length of stay (3.5 vs 4.3
      days, p = 0.294). Conclusions This is the first study in otolaryngology or
      neurosurgery to compare operative times and outcomes for AO versus TA cases at a
      single academic institution. Operative times were significantly decreased and a
      trend toward a decrease in patient morbidity was noted for cases performed solely
      by attendings. The valuation of teaching activities in the operating room is a
      necessary first step toward optimizing the allocation of resources and funding of
      surgical education. 

PMID- 24294559
TI  - Microsurgical localization of the cochlea in the extended middle fossa approach.
AB  - Objective In the extended middle fossa approach, a portion of the petrous bone
      known as Kawase's rhomboid can be drilled to expose the posterior fossa through a
      middle fossa corridor. During this bony resection, the cochlea is placed at risk.
      The objective of this study was to objectively detail the position of the cochlea
      in relation to reliable surgical landmarks. Methods Eleven cadaveric specimens
      were dissected-including six cadaveric heads and five dry temporal bones by means
      of an anterior petrosectomy with skeletonization of the cochlea. Three anatomic
      measurements describing the location of the cochlea in relation to the
      extrapolated intersection of the greater superficial petrosal nerve (GSPN) and
      facial nerve were recorded. These measurements were then correlated with thin-cut
      temporal bone computed tomography scans from 25 patients with morphologically
      normal inner ears. Results In the cadaveric specimens, the anterior border of the
      membranous basal turn of the cochlea was located an average of 7.56 mm (6.4 to
      8.9 mm) anterior to the extrapolated junction of the GSPN and facial nerve, as
      measured along the course of the GSPN. The medial border of the membranous
      cochlea (medial margin of basal turn) was located an average of 8.2 mm (6.9 to
      8.9 mm) medial to the extrapolated junction of the GSPN and facial nerve, as
      measured along the course of the facial nerve. The average maximum distance from
      the extrapolated junction of the GSPN and facial nerve to the membranous cochlea
      was 9.3 mm (8.2 to 10.3 mm). These anatomic measurements correlated well with
      radiologic measurements of the same parameters. Conclusion When drilling Kawase's
      rhomboid, it is useful to locate the extrapolated junction of the GSPN and the
      facial nerve. Drilling of the anteromedial petrous bone outside of a radius of
      12.5 mm from the extrapolated junction of GSPN and facial nerve appears to be
      associated with a low degree of risk to the cochlear apparatus. 

PMID- 24294560
TI  - Computer modeled multiportal approaches to the skull base.
AB  - Skull base surgical approaches have evolved significantly to minimize collateral
      tissue damage and improve access to complex anatomic regions. Many endoscopic
      surgical portals have been described, and these can be combined in multiportal
      approaches that permit improved angles for visualization and instrumentation. To
      assist in the choice of entry portal and surgical pathway analysis, a three
      dimensional computer model with virtual endoscopy was created. The model was
      evaluated on transnasal and transorbital approaches to access 11 specified sellar
      and parasellar target locations on 14 computed tomography (CT) scans. Data were
      collected on length of approach, angle between instruments, and approach angle
      with respect to anatomical planes. Optimal multiportal approach combinations were
      derived. The data demonstrated that the shortest, most direct pathway to many
      sellar and parasellar targets was through transorbital portals. Distances were
      reduced by 35% for certain target locations; combining transorbital and
      transnasal portals increased the angle between instruments 4-fold for many
      targets. The predicted values from the model were validated on four cadaver
      specimens. Computer modeling holds the potential to play an integral role in the
      design, analysis, and testing of new surgical approaches, as well as in the
      selection of optimal approach strategies for the unique pathology of individual
      patients. 

PMID- 24294561
TI  - Anatomic variation of the optic strut: classification schema, radiologic
      evaluation, and surgical relevance.
AB  - Objective Anatomic variability of the optic strut in location, orientation, and
      dimensions is relevant in approaching ophthalmic artery aneurysms and tumors of
      the anterior cavernous sinus, medial sphenoid wing, and optic canal. Methods In
      84 dry human skulls, imaging studies were performed (64-slice computed tomography
      [CT] scanner, axial view, aligned with the zygomatic arch). Optic strut location
      related to the prechiasmatic sulcus was classified as presulcal, sulcal,
      postsulcal, and asymmetric. Morphometric analysis was performed. Results The
      optic strut was presulcal in 11.9% specimens (posteromedial margin bilaterally
      anterior to limbus sphenoidale), sulcal in 44% (posteromedial part adjacent to
      the sulcus's anterior two thirds bilaterally), postsulcal in 29.8% (posteromedial
      margin posterior to the sulcus's anterior two thirds), and asymmetric
      (left/right) in 14.3%. Optic strut length, width, and thickness measured 6.54 +/-
      1.69 mm, 4.23 +/- 0.69 mm, and 3.01 +/- 0.79 mm, respectively. Optic canal
      diameter was 5.14 +/- 0.47 mm anteriorly and 4.79 +/- 0.64 mm posteriorly.
      Angulation was flat (>45 degrees) in 13% or acute (<45 degrees) in 87% specimens.
      Conclusions Anatomical variations in the optic strut are significant in planning
      for anterior clinoidectomy and optic-canal decompression. Our optic strut
      classification considers these variations relative to the prechiasmatic sulcus on
      preoperative imaging. 

PMID- 24294562
TI  - Dorello's Canal and Gruber's Ligament: Historical Perspective.
AB  - Wenzel Leopold Gruber and Primo Dorello were great anatomists and researchers
      during the 19th and 20th centuries. Their contributions to neuroanatomy-namely
      the Gruber's (petrosphenoidal) ligament and Dorello's canal, respectively-have
      come to be important structures in various approaches through the middle fossa.
      These structures have also helped provide us with an understanding of the
      mechanism of sixth nerve paresis in various pathological conditions, such as
      raised intracranial pressure and Gradenigo syndrome. Their numerous publications
      have stood as a reference to anatomical researchers. Gruber's description of
      internal mesogastric hernia and the Meckel-Gruber anastomosis are also widely
      known in medical literature. The following article is an attempt to reflect upon
      the life and works of Gruber and Dorello and the importance of their research. 

PMID- 24294563
TI  - Metastatic renal cell carcinoma to the sinonasal cavity: a case series.
AB  - Objectives To describe the presentation, work-up, and management of patients with
      metastatic renal cell carcinoma (RCC) to the sinonasal cavity and skull base, and
      to describe our current treatment algorithm of endoscopic surgical resection
      followed by radiation therapy. Design Retrospective review of two recent cases
      from our institution over a 1-year period, with a relevant review of the
      literature. Setting A large regional tertiary care facility. Participants
      Consecutive cases of RCC with metastases to the sinonasal cavity presenting to
      our institution. Main Outcome Measures Preoperative and postoperative sinonasal
      outcome test (SNOT)-22 scores, duration of hospital stay, complications, and
      local disease control Results Patients in this series underwent preoperative
      embolization followed by endoscopic resection without complication.
      Postoperatively they were treated with radiation therapy. They experienced
      improvement in their SNOT-22 scores and are currently free of local disease.
      Conclusion Metastatic RCC to the sinonasal cavity can be safely treated with
      preoperative embolization followed by endoscopic surgical resection and radiation
      therapy, which can result in improvement in sinonasal quality of life and is a
      potential adjunct for local control of disease. 

PMID- 24294564
TI  - Abnormality of the Foramen Spinosum due to a Variation in the Trajectory of the
      Middle Meningeal Artery: A Case Report in Human.
AB  - Originating from the maxillary artery, the middle meningeal artery (MMA) is
      predominantly periosteal irrigating the bone and dura mater. It enters the floor
      of the middle cranial fossa through the foramen spinosum, travels laterally
      through a middle fossa bony ridge, and curves over the previous upper-greater
      wing of the sphenoid, where it in a variable point is divided into frontal and
      parietal branches. The complex sequence of the MMA development gives many
      opportunities for variant anatomy. In a Caucasian cadaver skull of an
      approximately 35-year-old individual belonging to the didactical collection of
      the Laboratory of Human Anatomy at the University of Santa Cruz do Sul, Brazil,
      it was noted that the right foramen spinosum has an abnormal shape. In this
      report, we discuss an abnormality of the foramen spinosum due to a variation in
      the trajectory of the MMA. Thus, the present study shall be important for health
      sciences and those who have some interest in pathologies associated with the MMA.

PMID- 24294565
TI  - Endovascular treatment of a temporal bone pseudoaneurysm presenting as bloody
      otorrhea.
AB  - Objective This case report is designed to illustrate an uncommon presentation of
      osteoradionecrosis (ORN) of the temporal bone and a treatment method for bloody
      otorrhea from a pseudoaneurysm of the internal carotid artery (ICA). Design This
      is a single patient case report Setting University of Missouri-Columbia Hospital
      and Clinics. Participants The report describes a patient with a history of
      hypopharyngeal squamous cell carcinoma (SCCA) who was previously treated with
      chemoradiation therapy and salvage bilateral neck dissections and then presented
      in a delayed fashion with profuse, episodic bloody otorrhea. Computed tomography
      (CT) was consistent with ORN of the temporal bone. The patient underwent emergent
      cerebral angiography. A pseudoaneurysm of the cervicopetrous ICA was confirmed to
      be the source of the patient's bloody otorrhea. The lesion was treated by
      endovascular sacrifice of the ICA using the two-catheter coiling technique.
      Results The patient had no neurologic sequelae or further bleeding after
      treatment. Conclusions Bloody otorrhea is an uncommon presentation of ORN.
      Sacrifice of the internal carotid can be considered as a treatment when the
      source is pseudoaneurysmal. 

PMID- 24294566
TI  - Mature teratoma of the petrous bone with extension into the cerebellopontine
      angle: case report.
AB  - Purpose Intracranial teratomas in children involving lateral structures such as
      the petrous portion of the temporal bone are very uncommon. The authors report a
      case of a petrous teratoma with significant extension into the cerebellopontine
      angle with brainstem compression. Case Report An 11-year-old girl presented left
      sided facial weakness. Computed tomography (CT) demonstrated a multiloculated
      lesion expanding the labyrinthine structures in the left petrous temporal bone
      including the vestibule, semicircular canals, and cochlea, with extension to the
      left cerebellopontine angle via the expanded left internal auditory canal. The
      tumor was resected via a transtemporal approach with no evidence of recurrence at
      nearly 2 years. Conclusion Complete resection should be the primary treatment for
      these tumors to minimize the risk of recurrence. To the authors' knowledge, this
      is the first case report of a mature teratoma originating in the petrous bone
      with extension into the cerebellopontine angle. 

PMID- 24294567
TI  - Transpterygoid stent placement for management of a recurrent infratemporal fossa
      epidermoid cyst: a technical note.
AB  - Epidermoid cysts (ECs) are benign congenital cysts that typically develop from
      misplaced stratified squamous epithelium during neural tube closure. They are
      most commonly encountered in the cerebellopontine angle, the fourth ventricle,
      and the region of the sella turcica. Recurrence of an EC or regrowth of residual
      components following surgery is known to occur, but the exact incidence is not
      defined. Repeat surgical removal is generally considered but may be complicated
      by significant morbidity. We present a novel endoscopic method by which to manage
      a recurrent EC of the infratemporal fossa using a silastic stent through a
      transpterygoid approach that permits periodic drainage of recurrent cyst material
      in the outpatient setting with minimal morbidity. 

PMID- 24294568
TI  - The bethesda system for reporting thyroid cytopathology: interpretation and
      guidelines in surgical treatment.
AB  - OBJECTIVES: (1) The aim of this study is to assess the efficacy of The Bethesda
      System for Reporting Thyroid Cytology (TBSRTC) in accurate prediction of thyroid
      lesions on fine needle aspiration (FNA). (2) To appraise the surgeon with
      guidelines for adequacy of samples, and interpretation of FNA reports with TBSRTC
      and hence aiding them in surgical decision making. Five hundred and sixty four
      FNAs were done on patients with thyroid swellings in the department of Pathology
      and reported using TBSRTC guidelines. In cases where surgery was done,
      histopathological report was correlated. Using TBSRTC the commonest cytological
      diagnosis was benign-Hashimotos thyroiditis followed by benign follicular nodule.
      TBSTRC reduces inter-observer variability in reporting thyroid FNAs and provides
      good communication between the surgeon and pathologist. It also implicates
      guidelines for cancer risk and clinical management to the surgeons, thus avoiding
      unnecessary surgery.

PMID- 24294569
TI  - Nasal septal deviation and external nasal deformity: a correlative study of 100
      cases.
AB  - A prospective study of 100 consecutive patients of deviated nasal septum to
      analyze association of septal deviation with external nasal deformity was
      undertaken at Acharya Vinoba Bhave rural Hospital of Jawaharlal Nehru Medical
      College, Sawangi (Meghe) Wardha from January 2009 to September 2010. Nasal septal
      deviations were evaluated by clinical examination and diagnostic nasal endoscopy
      while external nasal deformities, after evaluating, were documented using high
      resolution photography Nasal septal deviations were classified in seven types
      from I to VII by using Mladina's classification modified by Janardhan et al. Jang
      classification was employed to classify external nasal deformities. 66% of the
      patients with deviated nasal septum were symptomatic while 34 lacked symptoms.
      Nasal obstruction was the most frequent symptom in 64% followed by nasal
      discharge in 33% Type VII was the most common type of deviation in 29%. Study
      revealed that 67% of the patients with deviated nasal septum had external nasal
      deformity and of the 67 patients with external deformity, Type I deformity was
      most frequent (26%). Remarkable feature of our study was Type I, III, V septal
      deviations were not associated with external deviation Type II septal deviations
      were commonly associated with Type III external deformity (7%) and Type IV septal
      deviation were closely associated with Type I external deformity (12%). 

PMID- 24294570
TI  - Intact canal wall tympanomastoid surgery: 10 years experience.
AB  - 310 cases of chronic middle ear disease were managed by Intact canal wall
      tympanomastoid surgery. Intact canal wall tympanomastoid surgery technique used
      in this study has been compared with the Jansen's classic ICW technique. A
      retrospective analysis of 310 cases of chronic middle ear pathology managed by
      Intact canal wall technique over a period of 10 years (January 1996 to December
      2005) was conducted. Patients information was collected from the patients record.
      310 patients, aged 5-60 years, were managed by Intact canal wall technique and
      followed for a minimum period of 5 years. The male:female ratio in our study was
      1.25:1 (172 males:138 females). The ratio of adult to pediatric patients was
      2.7:1 (226 adults:84 children). Out of 274 (88.4%) cases having a regular follow
      up, 196 (71.6%) were found to be stable. Postoperative retraction of the tympanic
      membrane was observed in 24 (8.8%) cases and was managed by the placement of
      ventilation tube. Secretory otitis media was seen in 14 (5%) cases and was
      managed by myringotomy and placement of ventilation tube. 17(12.4%) cases were
      revised including recurrent disease (10 cases), residual disease (6 cases), graft
      failure (12 cases), stenosis of the ear canal (4 cases), meatomastoid fistula (2
      case). Our technique of Intact canal wall tympanomastoid surgery takes less time
      than the classic Jansen's technique, is easily reproducible and taught, is a
      single stage procedure and can be universally applied to various chronic middle
      ear pathologies as the primary treatment with low recidivism rate. 

PMID- 24294571
TI  - A study of the bacteriological profile of chronic suppurative otitis media in
      agartala.
AB  - Chronic suppurative otitis media (CSOM) is one of the most commonly encountered
      diseases in otolaryngology practice. Even in this era of powerful antibiotics,
      CSOM still consumes considerable medical expenditure, especially in the poorer
      sections of the society. The present prospective study was conducted at the IGM
      Hospital, Agartala, in North East India towards clinico-microbiologic evaluation
      of chronic suppurative otitis media. The focus was mainly on aerobic bacteria,
      involved in active CSOM in adults as well as children. An attempt was made,
      despite resource and man power constraints, to have a glimpse of the current
      antibiotic sensitivity pattern, with special reference to ciprofloxacin. However,
      the main aim of this study is to see the types of aerobic bacteria involved in
      CSOM, in our region. Aural swabs were collected from 100 ears, from 97 patients
      complaining of ear discharge, continuous or intermittent, with a non- intact
      tympanic membrane for at least 12 weeks. Swabs were sent to the hospitals
      microbiology laboratory for culture and sensitivity tests. Bacteria could be
      isolated in 53 cases and 47 swabs were culture negative. The commonest bacteria
      isolated was pseudomonas (20) followed by Staphylococcus aureus (11), E. coli
      (11), proteus (9) and klebseilla (2). Three patients had bilateral ear discharge
      of which one had proteus in both ear swabs, one grew proteus in one ear and no
      growth in the other, and one patient showed no aerobic bacteria in any of his ear
      swabs. Among the culture positive cases (n = 53) gram negative bacteria were
      isolated in 79.24% (n = 42) and S. aureus in 11(20.75%) cases. Among 97 patients
      number of male and female patients was 50 and 47, respectively. Pseudomonas, E.
      coli, Bacilli proteus and S. aureus were the predominant bacteria involved in
      CSOM. Out of the 53 positive isolates ciprofloxacin could be tested against 35
      i.e., 66%. Ciprofloxacin was sensitive in 26 isolates, intermediately sensitive
      in 4 and resistant in only five isolates. It is concluded that, gram negative
      bacteria especially pseudomonas is the commonest bacteria involved in CSOM in
      this part of north east India. Ciprofloxacin is an important tool in the
      management of active CSOM as it is cheap, less ototoxic and widely available as
      topical preparations. 

PMID- 24294572
TI  - Factors influencing delayed presentation of congenitally hearing impaired
      children in rural India.
AB  - A study was conducted to determine why there was a delay in detection of hearing
      loss in congenitally hearing impaired children in rural India. It was found that
      although the parents of these children visited a primary care physician, relevant
      information regarding investigation and rehabilitation of hearing loss was not
      available to the patient. In the absence of a universal hearing screening
      programme in this country, it is a matter of importance to strengthen this aspect
      of community otolaryngology in the undergraduate ENT programme. There is also a
      need for continuing medical education programmes for primary care physicians
      regarding available methods of investigation and rehabilitation for a hearing
      impaired person. 

PMID- 24294573
TI  - Is Lidocaine Infiltration Really Necessary in Micro Ear Surgeries performed Under
      General Anaesthesia?
AB  - To study the role of infiltrating 2% Lidocaine in Micro ear surgeries performed
      under general anaesthesia. To measure the impact of infiltration of 2% Lidocaine
      in post operative pain relief and per operative bleeding. A Double blinded,
      Prospective randomized comparative study was conducted in a tertiary care
      referral centre. A total of 30 patients planned for micro ear surgeries under
      general anaesthesia (Tympanoplasty and Cortical mastoidectomy) for CSOM
      tubotympanic disease were selected and divided into two groups randomly by the
      chief senior consultant. Group A patients received local infiltration of 2%
      Lidocaine with one in 200,000 adrenaline and Group B patients received
      infiltration of one in 200,000 adrenaline in distilled water alone. Operating
      surgeon assessed the bleeding in the surgical field using Boezaart's grading
      system. Post operative pain was assessed using a visual analog scale. Pain scores
      of these patients were assessed in the 1st, 4 and 24th h post operatively and
      recorded. The mean post operative pain score in the 1st h for the patients in
      Group A was 0.93 and for patients in Group B was two. The difference in the pain
      scores between the two groups was significant (P < 0.02).The difference in the
      mean post operative pain scores between the two groups in the 4 and 24th h were
      not significant (P < 0.1).Per operatively, grade III bleeding was present in 73%
      of patients in group B and only 33% of patients had grade III bleeding in group
      A. Infiltration of 2% Lidocaine has a significant impact over the grade of
      bleeding in the operative field and also on 1st h post operative pain relief. It
      did not have a significant influence on the pain relief in the 4 and 24th h post
      operatively. 

PMID- 24294574
TI  - Assessment of nasal airflow resistance in the healthy population of chattisgarh
      by active anterior rhinomanometry.
AB  - The aim of present study was to define a normal range of total nasal airflow
      resistance in the healthy population of Chattisgarh. This study was conducted at
      the Department of Otorhinolaryngology, Medical College Raipur, Chattisgarh over
      93 healthy adults. A proper otolaryngology examination was done prior to the
      study and all the subjects were free from any type upper respiratory tract
      infection. This was the main inclusion criteria for the present study. All the
      subjects were distributed according to age and sex. Active Anterior
      Rhinomanometry is the best recommended method for evaluating the objective
      assessment of nasal airflow resistance; it was preferred for the assessment of
      total nasal airway resistance in present study also. The present study concluded
      that the mean value of total nasal airway resistance was 0.21 at 150 Pa pressure.
      However the range of total nasal airway resistance was from 0.142 to 0.34
      Pa/cm(3)/s at the same pressure. The present study presents the normal range and
      mean value of total nasal airway resistance for the healthy adult population of
      Chattisgarh. Total nasal airway resistance is independent of age and sex. 

PMID- 24294575
TI  - Modified technique of anterior nasal packing: a comparative study report.
AB  - Anterior nasal packing, which is a common procedure in otorhinolaryngology
      practice, has different complications. Pain during introduction and removal of
      pack, bleeding after removal due to mucosal damage and synechia formation are
      common among them. A continuous effort is going on worldwide to combat those by
      modifying the nature of pack material or inventing new materials for nasal
      packing. In the present study an effort was made to compare a new modification of
      conventional gauze pack by using aluminum foil prepared from the cover of suture
      materials as septal splint (to reduce the mucosal damage) with conventional gauze
      pack and another costly material, nasal tampon (merocel). Comparisons were done
      in terms of cost, efficacy and complications. Prospective hospital based
      interventional study. Patients were distributed into three groups according to
      the material used for anterior nasal packing. Comparisons were made in terms of
      cost of the material used, pain during introduction of pack, rise of systolic
      blood pressure, incidences of bleeding while pack in situ, incidences of bleeding
      after removal of pack that required repacking and incidences of synechia
      formation after pack removal. The episodes of bleeding while pack in situ, within
      first 48 h and forced for repacking was observed to be significantly more
      prevalent among nasal tampon groups (12.5%) of patients but only 2.1 and 2.4%
      with use of conventional gauze pack and our modification respectively. Regarding
      bleeding after removal of pack, 10.6% patients experienced bleeding with
      conventional gauze pack, whereas with our modification it was only 2.4%. Synechia
      formation was found to be highest among the cases with conventional gauze pack
      (14.9%), but with our modification it is only 2.4%. In this study it is found
      that use of aluminum foil prepared from the cover of suture materials can be very
      useful and cost effective method to reduce some of the complications of anterior
      nasal packing. 

PMID- 24294576
TI  - Nasal septal clips: an alternative to nasal packing after septal surgery?
AB  - Surgeons have debated since decades on the efficacy or inefficacy of nasal
      packing yet it is considered routine after septal surgery. Various types of
      septal splints have been tried as an alternative to nasal packs but most of them
      need to be sutured around the septum which requires a meticulous approach and
      expertise. Our aim is to assess and compare the immediate post-operative
      morbidity and the eventual outcome of septal surgery while using glove finger
      packs with that of septal clips with splints. This comparative study was done at
      MCV Memorial ENT Trust Hospital on 80 patients who were diagnosed to have DNS and
      underwent septal surgery. Patients were divided into two groups. Group A (n = 40)
      constituted of patients who had glove finger packs and Group B (n = 40)
      constituted of patients who had septal clips. In the immediate post-operative
      period patients were assessed for pain, headache, dysphagia, epiphora, dryness of
      mouth and post-operative bleed. On the first post-operative night, patients were
      assessed for oxygen saturation. Patients underwent tympanometry just before
      pack/splint removal and on reviews if the same was abnormal. Post-operative
      complications like septal perforation and synechiae were noted for both groups
      and compared. We found that the incidence of pain and various other signs and
      symptoms was significantly higher in Group A. The difference in the complication
      rates among the two groups was not statistically significant. We observed that
      nasal packing is a cause for significant morbidity and discomfort in the
      immediate post-operative period and does not give any added advantage over septal
      clips used in our study as far as the final outcome is concerned. Nasal septal
      clips with splints are a useful alternative to existing techniques of flap
      approximation after septal surgery. The method is not expensive and needs no
      special expertise. 

PMID- 24294577
TI  - Clinical and Audio Vestibular Profile of Meniere's Disease in a Tertiary Care
      Centre in India.
AB  - The aims of this study are to determine the frequency of patients presenting with
      Meniere's Disease(MD) in an Indian setting, using the American Academy of
      Otolaryngology-Head and Neck Surgery (AAO) diagnostic criteria, and to describe
      the clinical and audio vestibular profiles of these patients. The study was based
      on prospective case series design in the settings of a tertiary referral
      hospital. The study included all consecutive patients aged between 5 and 75 years
      presenting with the history of hearing loss, vertigo, tinnitus and or aural
      fullness as participants, satisfying inclusion and exclusion criteria for MD (AAO
      1995) recruited over a 12 month period. Main outcome measures comprised the
      evaluation of epidemiological profile, clinical features, and results of audio
      vestibular investigations like Pure Tone Audiometry with and without glycerol,
      Impedance Audiometry, Electrocochleography (ECohG), Distortion Product
      Otoacoustic Emission and Electronystagmography (ENG). The results of the study
      are as follows: The frequency of MD was 15.6%, being commoner in males than
      females (2.6:1) and occurring more in the age group 40-49  years among males and
      30-39 years among females. High frequency tinnitus was commoner than low
      frequency tinnitus. Extra tympanic ECohG had a positive predictive value of 76%
      for endolymphatic hydrops. ENG was useful for demonstrating canal paresis pattern
      of nystagmus in 61%. Indian patients with MD commonly present to tertiary care at
      the functional level scale of 3. The results of this study revealed that the
      frequency of MD is not as low in the Indian ENT setting as earlier believed.
      There is a high chance of missing cases in the routine ENT outpatient clinic
      setting unless a structured proforma incorporating the AAO 1995 diagnostic
      criteria is used. 

PMID- 24294578
TI  - Hearing loss in patients of chronic renal failure: a study of 100 cases.
AB  - The purpose of our study was to determine the incidence of hearing loss and to
      describe the hearing impairment and the possible contributing factors,
      responsible for sensori neural hearing loss in chronic renal failure (CRF)
      patients. This was a prospective study carried out on 50 cases of CRF attending
      otorhinolaryngological services for hearing disturbance and on 50 healthy
      volunteers for control study, having the same inclusion criteria except (does not
      suffering with CRF) having normal renal function tests. These volunteers attended
      the ENT OPD, for oto-rhino-laryngological services but not for hearing problems.
      14 (28%) out of 50 cases of CRF had sensori neural hearing loss of moderate to
      severe degree in the high frequency range which was bilateral and symmetrical,
      while in control group the incidence of sensorineural hearing loss was only 6%. 

PMID- 24294579
TI  - A comparative study of trained and untrained rabindrasangeet singers.
AB  - This scientific paper proposes an analytic framework specifically for
      Rabindrasangeet singing that models the time-varying physical and expressive
      characteristics unique to an individual voice through a phonetogram analysis. The
      present study incorporates the most popular Rabindrasangeet into account for
      analysis to get an idea about the specific numerical data regarding the
      fundamental frequency, semitones, SPL range, and area as well as to give a
      precise guideline to those clients. While comparing the trained and untrained
      singers both males and females the F0 parameter is found to be louder in trained
      group. The mean semitone is always higher in females than in males and the
      trained male subjects have significantly higher SPL range than trained female
      subjects and trained females have higher SPL range than untrained female
      subjects. The enclosed area is larger in trained singers and more in females than
      males. Results of this study indicate differences between untrained and trained
      phonetograms. These differences can be attributed to greater natural capacities
      in trainedsubjects or a superior learned control over the voice mechanism. 

PMID- 24294580
TI  - Rheumatoid factor and hearing loss.
AB  - To find out the association between rheumatoid factor and hearing loss, a
      prospective study was conducted at Tertiary care/Medical college hospital. We
      screened 85 patients with positive rheumatoid factor for evidence of hearing
      loss. These patients were collected from the Departments of Medicine and
      Orthopedics. Out of 85 patients, who were positive for rheumatoid factor,
      underwent screening for hearing loss. These patients had a normal pure tone
      audiogram but Distortion product otoacoustic emission (DPOAE) was absent in
      twenty three patients. DPOAE was absent in 27% of cases, in whom there was
      positive rheumatoid factor. It was extremely statistically significant. 

PMID- 24294581
TI  - Endoscopic Endonasal Dacryocystorhinostomy: Best Surgical Management for DCR.
AB  - EEDCR is a highly rewarding Endoscopic procedure for management of dacryocystitis
      when epiphora does not respond to medications or repeated syringing of
      nasolacrimal duct. It is a simple, less time consuming, safe but skilful, highly
      satisfying surgery both for the patients as well as the surgeons. There is very
      big advantage of EEDCR, it is close 100% successful procedure, even if there is
      recurrence of epiphora it is again correctable fully with no residual affects.
      EEDCR is far more superior to External DCR/Laser DCR and there are definite
      reasons for it. A total number of 578 cases have been operated by me from April
      1, 2005 to March 31, 2011, only very few reoccurrences were there and they were
      corrected easily so much so that it can be said that it is a close 100%
      successful procedure and best surgical management of DACRYOCYSTITIS up to date.
      The successful outcome was defined as symptomatic relief from epiphora and
      dacryocystitis and a patent nasolacrimal duct upon syringing at the end of
      procedure and on follow up of patient. 

PMID- 24294582
TI  - Arteriovenous malformation of nose-revision surgery.
AB  - Areteriovenous malformations are rare in the head and neck region and generally
      arise from intracranial vessels. We present one rare case with spontaneous
      arteriovenous malformations related to the nose. 

PMID- 24294583
TI  - Relevance of Pure Tone Average (PTA) as a Predictor for Incus Erosion.
AB  - Between 40 and 90% of tympanoplasty require middle ear ossicular chain
      reconstruction. Ossicular discontinuity usually cannot be determined unless an
      operation is performed. The main objective was to determine the predictive value
      of pre-operative audiological factors in diagnosing incudal necrosis in patients
      with tubotympanic chronic suppurative otitis media. A retrospective clinical
      study of 20 patients who underwent ossicular reconstruction with autologous incus
      over a period of two years was performed. The mean pre-operative pure tone
      average was 49.18 dB HL.The minimum value being 45 dB HL and the maximum value
      being 64 dB HL. 

PMID- 24294584
TI  - Pre-Operative and Post-Operative Assessment of Hearing following Tympanoplasty.
AB  - Tympanoplasty is one of the ever evolving surgical procedures mainly aimed at
      restoring the hearing loss and eradication of middle ear disease. We have made an
      attempt to assess the hearing improvement of various types and techniques of
      tympanoplasty. A prospective observational study was done on 50 cases of CSOM, of
      which 45 cases were tubotympanic type, and 5 cases were attico-antral. Patients
      of only pure conductive component with good cochlear reserve and good Eustachian
      tube function were considered for the study. This study aims at assessing the
      hearing improvement with various types of tympanoplasty. 

PMID- 24294585
TI  - Impact of anatomical and radiological findings for consideration of functional
      endoscopic sinus surgery.
AB  - Endoscopic sinus surgery is being done more accurately and with better diagnosis
      and planning with the help of high resolution CT scan. It has played an
      invaluable role in the delineation of the sinonasal pathology and anatomic
      variations preoperatively. To correlate the CT scan findings with endoscopic
      findings with respect to anatomical variants and pathology and evaluation of its
      impact on surgical planning. A prospective study conducted on 300 patients who
      presented to the ENT out patient department with sinonasal diseases and underwent
      Functional endoscopic sinus surgery. There is a need to evaluate and correlate
      the findings to deduce the extent of relations CT findings have to that of
      findings observed during endoscopy as they really affect the surgical planning
      and outcomes. 

PMID- 24294586
TI  - Clinical importance of duplication of internal jugular vein.
AB  - Duplication of internal jugular vein (IJV) is rare. It is the larger channel
      draining the cranial cavity. We encountered duplication of the IJV while cervical
      node clearance in a patient with squamous cell carcinoma of left margin of the
      tongue. IJV divides into two parts anterior and posterior after descending about
      2.5 cm from the jugular foramen. IJV is an important landmark in neck surgery.
      Knowledge of its variations is essential to avoid complications during surgery
      and to avoid misinterpretation in CT angiography. 

PMID- 24294587
TI  - A study of closure of tympanic membrane perforations by chemical cauterisation.
AB  - To study the effectiveness of chemical cautery with patching on chronic tympanic
      membrane perforations of the pars tensa. Thirty-eight patients with dry tympanic
      membrane perforations due to inflammatory or traumatic etiology were selected
      after treating the primary etiological factors like septal deviation and allergic
      rhinitis. Fifty percentage silver nitrate was used to cauterize the margin and
      the perforation was covered with thin sterile aluminium foil as a patch. A
      maximum number of five applications were made, and the patients were followed up
      for the next 5 years. In this series of 38 patients, highest success was noted
      among those patients with traumatic perforation, while larger perforations were
      reduced to small pinhole sizes which were successfully closed by myringoplasty.
      An overall success rate of 73.75% was achieved. This is a time tested useful
      method which was popularized by Derlacki (1953), to close small to moderate sized
      tympanic membrane perforation and should be considered as a first line management
      in the treatment of tympanic membrane perforation prior to any surgical
      intervention. Apart from being a simple and economical mode of treatment, it is
      associated with minimal complications. Though various materials have been used to
      modify this technique, the principle remains the same and the results obtained in
      this study is comparable with the previous ones. 

PMID- 24294588
TI  - Postoperative histological changes in polypose rhinosinusitis.
AB  - The aim of this study was to evaluate the effect of surgery on the histology of
      nasal mucosa in patients with nasal polyposis and the comparison/also to compare
      it with normal population. This case-control study was conducted on 20 patients
      at the Otorhinolaryngology-Head and Neck Surgery Department, Qaem Hospital,
      Mashhad University of Medical Sciences during October 2007 to June 2008. Patients
      with polyposis and patients with septal deviation who were candidate for
      septoplasty were considered as case and control groups, respectively, including
      10 subjects in each. Specimens of polyp tissue and the inferior conchae (mucosa)
      were taken during sinus endoscopy from the case group. One month later, another
      specimen was taken from the inferior conchae (mucosa). Moreover, specimens of the
      inferior conchae (mucosa) were taken of the control group. Percentage of goblet
      cells among the epithelial cells was determined for each group. Goblet cell
      percentage found to be 15.7% in polyps, consistent with significant difference
      with that of in postoperative (13.3%) and in preoperative nasal mucosa specimens
      (39.86%), (P = 0.043 and P = 0.03, respectively). Goblet cell percentage was
      39.86% and 4.9% in the case and control groups, in that order, which were
      significantly high (P < 0.001). Percentage of goblet cells showed to be lower in
      polyps than mucosa. Also percentage of goblet cells in postoperative nasal mucosa
      specimens was significantly lower than preoperative specimens. Therefore, surgery
      has additional benefit of histological improvement rather than opening nasal
      airway. 

PMID- 24294589
TI  - Rare case of temporal bone carcinoma with intracranial extension.
AB  - Temporal bone cancer, a relatively rare disease, accounting for less than 0.2% of
      all tumors of the head and neck and is associated with a poor outcome; often
      presents in a subtle manner, which may delay diagnosis. It should be suspected in
      any case of persistent otitis media or otitis externa that fails to improve with
      adequate treatment. Despite advances in operative technique and postoperative
      care, long-term survival remains poor). It includes cancers arising from pinna
      that spreads to the temporal bone, primary tumors of the external auditory canal
      (EAC), middle ear, mastoid, petrous apex, and metastatic lesions to the temporal
      bone. Here is a report on a case of temporal bone carcinoma presenting with right
      otalgia, otorrhea and facial paralysis. The patient was initially diagnosed as
      mastoiditis and later the clinical impression was revised to temporal bone
      carcinoma (undifferentiated type), based on the pathologic findings. 

PMID- 24294590
TI  - Radical management of giant ameloblastomas: a case series.
AB  - Ameloblastomas are rare, slowly growing and locally invasive tumours with high
      recurrence rate, if not treated they can grow to enormous size; we report five
      such cases in our article and discuss their surgical management. We report five
      cases of giant ameloblastoma presented in our institute between 2007 and 2010, we
      treated them surgically with wide margin of resection. It is widely reported that
      recurrence of ameloblastoma in many cases reflects the inadequacy or failure of
      the primary surgical procedure. We treated all our cases with radical excision
      with free flap reconstruction with no recurrence in any of our patients in 2
      years follow-up. Radical excision of these benign but locally invasive lesions,
      which grows to giant size with reconstruction using micro vascular free flaps
      forms the best modality of treatment. 

PMID- 24294591
TI  - The role of postoperative radiation and chemoradiation in merkel cell carcinoma:
      a systematic review of the literature.
AB  - OBJECTIVE: A systematic review of the literature was undertaken to investigate
      whether adjuvant radiotherapy and/or chemotherapeutics offered any additional
      benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC).
      METHODS: A PubMed, MEDLINE search was conducted between 1995 and 2013, to
      identify reported cases of surgically treated MCC followed by either observation,
      radiation, or chemoradiation. Patient demographics and outcomes were recorded and
      compared in a systematic fashion. RESULTS: Thirty-four studies (n = 4475) were
      included. The median age was 73 years, median follow up was 36 months and there
      was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no
      further treatment, 1689 received postoperative RT, and 301 received postoperative
      chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most
      common clinical stage at diagnosis (57%). Three-year local control was 20%
      (median 10%) in the observation cohort, compared to 65% (62%) with postoperative
      RT, and 67% (75%) with postoperative chemoRT; these findings were statistically
      significant (P < 0.001). Recurrence was found to be 38% (60%) in the observation
      cohort, compared to 23% (20%) with postoperative RT (P < 0.001). Three-year
      overall survival (OS) was found to be 56% (57%) in the observation cohort,
      compared to 70% (78%) with postoperative RT and 73% (76%) with postoperative
      chemoRT (P < 0.001). The observation cohort had a median OS of 44 months compared
      with 64 months (P < 0.001) in the postoperative RT cohort. There was no
      statistically significant difference in any parameters assessed between
      postoperative radiation and postoperative chemoradiation arms. CONCLUSION: The
      comprehensive collection of retrospective data suggests a survival and control
      benefit for postoperative radiation in MCC. No differences were noted between
      adjuvant radiation and chemoradiation. This analysis indicates the need for
      prospective trials with patients stratified by known prognostic factors.

PMID- 24294592
TI  - PARP Inhibitors in Cancer Therapy: Magic Bullets but Moving Targets.

PMID- 24294593
TI  - Pseudomonas aeruginosa adapts its iron uptake strategies in function of the type
      of infections.
AB  - Pseudomonas aeruginosa is a Gram-negative gamma-Proteobacterium which is known
      for its capacity to colonize various niches, including some invertebrate and
      vertebrate hosts, making it one of the most frequent bacteria causing
      opportunistic infections. P. aeruginosa is able to cause acute as well as chronic
      infections and it uses different colonization and virulence factors to do so.
      Infections range from septicemia, urinary infections, burn wound colonization,
      and chronic colonization of the lungs of cystic fibrosis patients. Like the vast
      majority of organisms, P. aeruginosa needs iron to sustain growth. P. aeruginosa
      utilizes different strategies to take up iron, depending on the type of infection
      it causes. Two siderophores are produced by this bacterium, pyoverdine and
      pyochelin, characterized by high and low affinities for iron respectively. P.
      aeruginosa is also able to utilize different siderophores from other
      microorganisms (siderophore piracy). It can also take up heme from hemoproteins
      via two different systems. Under microaerobic or anaerobic conditions, P.
      aeruginosa is also able to take up ferrous iron via its Feo system using redox
      cycling phenazines. Depending on the type of infection, P. aeruginosa can
      therefore adapt by switching from one iron uptake system to another as we will
      describe in this short review. 

PMID- 24294595
TI  - Angiopoietin-like 3 induces podocyte F-actin rearrangement through integrin
      alpha(V)beta3/FAK/PI3K pathway-mediated Rac1 activation.
AB  - Glomerular podocytes are highly differentiated cells whose foot processes, which
      are mainly maintained by the architecture of actin filaments, have a unique
      morphology. A rearrangement of F-actin in podocytes causes changes in their
      motility that involve foot process effacement and proteinuria in glomerular
      diseases. Members of the Rho family small GTPases, especially RhoA, Rac1, and
      Cdc42, are key molecules in the regulation of actin cytoskeleton rearrangement.
      Our previous study showed that angiopoietin-like 3 (Angptl3) can increase the
      motility of podocytes in vitro. In this study, we found that recombinant Angptl3
      treatment, together with the activation of Rac1, could cause F-actin
      rearrangement in podocytes. We also found that these effects could be blocked by
      an integrin alpha(V)beta3 inhibitor, implicating integrin alpha(V)beta3 as the
      Angptl3 receptor in its effects on actin cytoskeleton rearrangement. In addition,
      we studied the molecular pathway for this process. Our results showed that in
      podocytes, Angptl3 could induce actin filament rearrangement, mainly in
      lamellipodia formation, and that this process was mediated by integrin
      alpha(V)beta3-mediated FAK and PI3K phosphorylation and Rac1 activation. Our
      results might provide a new explanation for the effect of Angptl3 on increasing
      podocyte motility.

PMID- 24294594
TI  - Bloodstream form pre-adaptation to the tsetse fly in Trypanosoma brucei.
AB  - African trypanosomes are sustained in the bloodstream of their mammalian hosts by
      their extreme capacity for antigenic variation. However, for life cycle
      progression, trypanosomes also must generate transmission stages called stumpy
      forms that are pre-adapted to survive when taken up during the bloodmeal of the
      disease vector, tsetse flies. These stumpy forms are rather different to the
      proliferative slender forms that maintain the bloodstream parasitaemia. Firstly,
      they are non proliferative and morphologically distinct, secondly, they show
      particular sensitivity to environmental cues that signal entry to the tsetse fly
      and, thirdly, they are relatively robust such that they survive the changes in
      temperature, pH and proteolytic environment encountered within the tsetse midgut.
      These characteristics require regulated changes in gene expression to pre-adapt
      the parasite and the use of environmental sensing mechanisms, both of which allow
      the rapid initiation of differentiation to tsetse midgut procyclic forms upon
      transmission. Interestingly, the generation of stumpy forms is also regulated and
      periodic in the mammalian blood, this being governed by a density-sensing
      mechanism whereby a parasite-derived signal drives cell cycle arrest and cellular
      development both to optimize transmission and to prevent uncontrolled parasite
      multiplication overwhelming the host. In this review we detail recent
      developments in our understanding of the molecular mechanisms that underpin the
      production of stumpy forms in the mammalian bloodstream and their signal
      perception pathways both in the mammalian bloodstream and upon entry into the
      tsetse fly. These discoveries are discussed in the context of conserved
      eukaryotic signaling and differentiation mechanisms. Further, their potential to
      act as targets for therapeutic strategies that disrupt parasite development
      either in the mammalian bloodstream or upon their transmission to tsetse flies is
      also discussed. 

PMID- 24294596
TI  - A recombinant multiepitope protein for hepatitis B diagnosis.
AB  - Hepatitis B is a liver inflammation caused by hepatitis B virus (HBV) and can be
      diagnosed in clinical stage by hepatitis B core antibody from IgM class (anti
      HBcIgM). Hepatitis B core antibody from IgG class (Anti-HBcIgG) appears quickly
      after IgM, reaching high titers in chronic hepatitis, and remains even after
      cure. Since hepatitis B core antibody (anti-HBc) is the first antibody identified
      and sometimes the only marker detected during the course of infection, it can be
      used both to indicate HBV acute infection (anti-HBc-IgM) and to identify
      individuals who have come into contact with the virus (anti-HBc-IgG). In this
      work we propose a recombinant hepatitis B core multiepitope antigen (rMEHB) to be
      used for diagnosis of hepatitis B. For this purpose, a synthetic gene coding for
      rMEHB was designed and cloned into vector pET21a with a 6xHis tag at the C
      terminal. Time course induction in E. coli showed an induced protein with an
      apparent molecular mass of ~21 kDa. Protein purification was performed by a
      single step with affinity chromatography Ni-NTA. Circular dichroism spectroscopy
      indicated rMEHB as a thermal stable protein at pH 7.0 and 8.0. In these
      conditions rMEHB was successfully used to perform an enzyme linked immuno sorbent
      assay (ELISA) with positive and negative sera. 

PMID- 24294597
TI  - Anthropometric measurements of the human distal femur: a study of the adult Malay
      population.
AB  - The distal femurs of 100 subjects (50 men, 50 women) from the Malay population
      aged between 19 and 38 years were scanned to measure the anterior-posterior (AP)
      and medial-lateral (ML) width. The mean AP values were 64.02 +/- 3.38 mm and
      57.33 +/- 3.26 mm for men and women, respectively, and the mean ML values were
      74.91 +/- 3.52 mm and 64.53 +/- 3.07 mm. We compared our data to that published
      previously for the Chinese and Indian populations. It was found that the Malay
      population had smaller distal femur than that of the Chinese but was larger than
      that of the Indian population (P < 0.05). In conclusion, although it is well
      established that Asians have a smaller distal femur size than that of the Western
      population, the variations in different Asian ethnicities may need to be
      considered when designing the appropriate knee implant. 

PMID- 24294598
TI  - Safety assessment and biological effects of a new cold processed SilEmulsion for
      dermatological purpose.
AB  - It is of crucial importance to evaluate the safety profile of the ingredients
      used in dermatological emulsions. A suitable equilibrium between safety and
      efficacy is a pivotal concern before the marketing of a dermatological product.
      The aim was to assess the safety and biological effects of a new cold processed
      silicone-based emulsion (SilEmulsion). The hazard, exposure, and dose-response
      assessment were used to characterize the risk for each ingredient. EpiSkin assay
      and human repeat insult patch tests were performed to compare the theoretical
      safety assessment to in vitro and in vivo data. The efficacy of the SilEmulsion
      was studied using biophysical measurements in human volunteers during 21 days.
      According to the safety assessment of the ingredients, 1,5-pentanediol was an
      ingredient of special concern since its margin of safety was below the threshold
      of 100 (36.53). EpiSkin assay showed that the tissue viability after the
      application of the SilEmulsion was 92 +/- 6% and, thus considered nonirritant to
      the skin. The human studies confirmed that the SilEmulsion was not a skin
      irritant and did not induce any sensitization on the volunteers, being safe for
      human use. Moreover, biological effects demonstrated that the SilEmulsion
      increased both the skin hydration and skin surface lipids. 

PMID- 24294599
TI  - Gene therapy and cell-based therapies for therapeutic angiogenesis in peripheral
      artery disease.
AB  - Gene therapy and cell-based therapy have emerged as novel therapies to promote
      therapeutic angiogenesis in critical limb ischemia (CLI) caused by peripheral
      artery disease (PAD). Although researchers initially focused on gene therapy
      using proangiogenic factors, such as vascular endothelial growth factor (VEGF),
      fibroblast growth factor (FGF), and hepatocyte growth factors (HGF), cell therapy
      using bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (BMMSCs), G
      CSF-mobilized peripheral blood mononuclear cells (M-PBMNCs), and endothelial
      progenitor cells (EPCs) have also been extensively studied. Based on the
      elaborate studies and favorable results of basic research, some clinical phase
      I/II trials have been performed, and the results demonstrate the safety of these
      approaches and their potential for symptomatic improvement in CLI. However, the
      phase 3 clinical trials have thus far been limited to gene therapy using the HGF
      gene. Further studies using well-designed larger placebo-controlled and long-term
      randomized control trials (RCTs) will clarify the effectiveness of gene therapy
      and cell-based therapy for the treatment of CLI. Furthermore, the development of
      efficient gene transfer systems and effective methods for keeping transplanted
      cells healthy will make these novel therapies more effective and ease the
      symptoms of CLI. 

PMID- 24294600
TI  - Demethylation of cancer/testis antigens and CpG ODN stimulation enhance dendritic
      cell and cytotoxic T lymphocyte function in a mouse mammary model.
AB  - BACKGROUND: Cancer/testis antigens (CTAs) are ideal targets for cancer
      immunotherapy in virtue of their restricted expression profile in normal tissues.
      However, CTA-targeted immunotherapy has been rather disappointing clinical
      setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG)
      methylation in their promoter regions, so that tumor cells have low
      immunogenicity. METHODS: We reinduced mouse CTA P1A through demethylation process
      and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H
      2(d)) mice with dendritic cells pulsed with a P1A-specific peptide and CpG
      oligodeoxynucleotide (ODN) immune adjuvant. RESULTS: We found that demethylation
      and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced
      the allogenic capacity of P1A-specific CTLs against target cells both in vitro
      and in vivo. CONCLUSIONS: Our results suggested that CTA induction and immune
      adjuvant stimulation is a feasible strategy in cancer immunotherapy.

PMID- 24294601
TI  - Exploring different virtual screening strategies for acetylcholinesterase
      inhibitors.
AB  - The virtual screening problems associated with acetylcholinesterase (AChE)
      inhibitors were explored using multiple shape, and structure-based modeling
      strategies. The employed strategies include molecular docking, similarity search,
      and pharmacophore modeling. A subset from directory of useful decoys (DUD)
      related to AChE inhibitors was considered, which consists of 105 known inhibitors
      and 3732 decoys. Statistical quality of the models was evaluated by enrichment
      factor (EF) metrics and receiver operating curve (ROC) analysis. The results
      revealed that electrostatic similarity search protocol using EON (ET_combo)
      outperformed all other protocols with outstanding enrichment of >95% in top 1%
      and 2% of the dataset with an AUC of 0.958. Satisfactory performance was also
      observed for shape-based similarity search protocol using ROCS and PHASE. In
      contrast, the molecular docking protocol performed poorly with enrichment factors
      <30% in all cases. The shape- and electrostatic-based similarity search protocol
      emerged as a plausible solution for virtual screening of AChE inhibitors. 

PMID- 24294602
TI  - Epiretinal membranes in patients with uveitis: morphological and functional
      analysis with spectral domain optical coherence tomography.
AB  - PURPOSE: To correlate the uveitic epiretinal membrane (ERM) features using
      spectral-domain optical coherence tomography (SD-OCT) with visual acuity (VA).
      METHODS: Forty-one eyes of 32 patients were included in this retrospective study.
      SD-OCT was performed in all patients and data were collected at the time of ERM
      diagnosis and at the final visit. Both best corrected visual acuity (BCVA) and
      ERM thickness were correlated with the morphological and clinical features.
      RESULTS: Final BCVA was positively correlated with male sex (P = 0.0055) and the
      focal pattern of ERM attachment (P = 0.031) and negatively correlated with IS/OS
      photoreceptor junction disruption (P = 0.042). BVCA change showed a positive
      correlation with the age of ERM onset (P = 0.056) but a negative correlation with
      IS/OS photoreceptor disruption at the ERM diagnosis (P = 0.029) and the increase
      of central subfield thickness (CST) (P = 0.95). Final ERM thickness correlated
      with the duration of uveitis (P = 0.0023) and the duration of ERM (P = 1.15  e
      05). During the follow-up, ERM thickening correlated with male sex (P = 0.042),
      posterior uveitis (P = 0.036), uveitis duration (P = 0.026), and broad attachment
      pattern (P = 0.052). CONCLUSIONS: In the uveitic ERM, VA negatively correlates
      with IS/OS photoreceptor junction disruption and the increase of CST. ERM
      thickness is influenced by longer duration of both uveitis and ERM.

PMID- 24294603
TI  - Similar-case-based optimization of beam arrangements in stereotactic body
      radiotherapy for assisting treatment planners.
AB  - OBJECTIVE: To develop a similar-case-based optimization method for beam
      arrangements in lung stereotactic body radiotherapy (SBRT) to assist treatment
      planners. METHODS: First, cases that are similar to an objective case were
      automatically selected based on geometrical features related to a planning target
      volume (PTV) location, PTV shape, lung size, and spinal cord position. Second,
      initial beam arrangements were determined by registration of similar cases with
      the objective case using a linear registration technique. Finally, beam
      directions of the objective case were locally optimized based on the cost
      function, which takes into account the radiation absorption in normal tissues and
      organs at risk. The proposed method was evaluated with 10 test cases and a
      treatment planning database including 81 cases, by using 11 planning evaluation
      indices such as tumor control probability and normal tissue complication
      probability (NTCP). RESULTS: The procedure for the local optimization of beam
      arrangements improved the quality of treatment plans with significant differences
      (P < 0.05) in the homogeneity index and conformity index for the PTV, V10, V20,
      mean dose, and NTCP for the lung. CONCLUSION: The proposed method could be usable
      as a computer-aided treatment planning tool for the determination of beam
      arrangements in SBRT.

PMID- 24294604
TI  - Medium-level laser in chronic tinnitus treatment.
AB  - The purpose of this study was to evaluate the effect of medium-level laser
      therapy in chronic tinnitus treatment. In a prospective double-blind placebo
      controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode
      laser) or placebo irradiation was applied through the external acoustic meatus of
      the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus
      were studied. The main outcome was measured using the Goebel tinnitus
      questionnaire, visual analogue scales measuring the perceived loudness of
      tinnitus, the annoyance associated with tinnitus, and the degree of attention
      paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and
      loudness. The results did show only very moderate temporary improvement of
      tinnitus. Moreover, no statistically relevant differences between laser and
      placebo group could be found. We conclude that medium-level laser therapy cannot
      be regarded as an effective treatment of chronic tinnitus in our therapy regime
      considering the limited number of patients included in our study. 

PMID- 24294605
TI  - Response of C2C12 myoblasts to hypoxia: the relative roles of glucose and oxygen
      in adaptive cellular metabolism.
AB  - BACKGROUND: Oxygen and glucose are two important nutrients for mammalian cell
      function. In this study, the effect of glucose and oxygen concentrations on C2C12
      cellular metabolism was characterized with an emphasis on detecting whether cells
      show oxygen conformance (OC) in response to hypoxia. METHODS: After C2C12 cells
      being cultured in the levels of glucose at 0.6 mM (LG), 5.6 mM (MG), or 23.3
      mM(HG) under normoxic or hypoxic (1% oxygen) condition, cellular oxygen
      consumption, glucose consumption, lactate production, and metabolic status were
      determined. Short-term oxygen consumption was measured with a novel oxygen
      biosensor technique. Longer-term measurements were performed with standard
      glucose, lactate, and cell metabolism assays. RESULTS: It was found that oxygen
      depletion in normoxia is dependent on the glucose concentration in the medium.
      Cellular glucose uptake and lactate production increased significantly in hypoxia
      than those in normoxia. In hypoxia the cellular response to the level of glucose
      was different to that in normoxia. The metabolic activities decreased while
      glucose concentration increased in normoxia, while in hypoxia, metabolic activity
      was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was
      not observed in the present study. CONCLUSIONS: Our findings suggested that a
      combination of low oxygen and low glucose damages the viability of C2C12 cells
      more seriously than low oxygen alone. In addition, when there is sufficient
      glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic
      respiration, as shown by lactate production.

PMID- 24294606
TI  - Monocyte locomotion inhibitory factor produced by E. histolytica improves motor
      recovery and develops neuroprotection after traumatic injury to the spinal cord.
AB  - Monocyte locomotion inhibitory factor (MLIF) is a pentapeptide produced by
      Entamoeba histolytica that has a potent anti-inflammatory effect. Either MLIF or
      phosphate buffered saline (PBS) was administered directly onto the spinal cord
      (SC) immediately after injury. Motor recovery was evaluated. We also analyzed
      neuroprotection by quantifying the number of surviving ventral horn motor neurons
      and the persistence of rubrospinal tract neurons. To evaluate the mechanism
      through which MLIF improved the outcome of SC injury, we quantified the
      expression of inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and
      transforming growth factor- beta (TGF- beta ) genes at the site of injury.
      Finally, the levels of nitric oxide and of lipid peroxidation were also
      determined in peripheral blood. Results showed that MLIF improved the rate of
      motor recovery and this correlated with an increased survival of ventral horn and
      rubrospinal neurons. These beneficial effects were in turn associated with a
      reduction in iNOS gene products and a significant upregulation of IL-10 and TGF-
      beta expression. In the same way, MLIF reduced the concentration of nitric oxide
      and the levels of lipid peroxidation in systemic circulation. The present results
      demonstrate for the first time the neuroprotective effects endowed by MLIF after
      SC injury. 

PMID- 24294609
TI  - The use of carbon nanotubes to reinforce 45S5 bioglass-based scaffolds for tissue
      engineering applications.
AB  - Bioglass has been used for bone-filling material in bone tissue engineering, but
      its lean mechanical strength limits its applications in load-bearing positions.
      Carbon nanotubes (CNTs), with their high aspect ratio and excellent mechanical
      properties, have the potential to strengthen and toughen bioactive glass material
      without offsetting its bioactivity. Therefore, in this research, multiwall carbon
      nanotube (MWCNT)/45S5 Bioglass composite scaffolds have been successfully
      prepared by means of freeze casting process. 45S5 Bioglass was synthesized by the
      sol-gel processing method. The obtained material was characterized with X-ray
      powder diffraction (XRD). The mechanical properties of the scaffolds, such as
      compression strength and elastic modulus, were measured. Finally, compared with
      the scaffolds prepared by 100% 45S5 Bioglass powders, the addition of 0.25 wt.%
      MWCNTs increases the compressive strength and elastic modulus of 45S5 Bioglass
      scaffolds from 2.08 to 4.56 MPa (a 119% increase) and 111.50 to 266.59 MPa (a
      139% increase), respectively. 

PMID- 24294607
TI  - Recent advances in genetic predisposition of myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of
      autoantibodies that bind to components of the neuromuscular junction, causing the
      symptoms of muscular weakness and fatigability. Like most autoimmune disorders,
      MG is a multifactorial, noninherited disease, though with an established genetic
      constituent. The heterogeneity observed in MG perplexes genetic analysis even
      more, as it occurs in various levels, including diverse autoantigens, thymus
      histopathology, and age at onset. In this context of distinct subgroups, a
      plethora of association studies, discussed in this review, have assessed the
      involvement of various HLA and non-HLA related loci in MG susceptibility, over
      the past five years. As expected, certain HLA alleles were strongly associated
      with MG. Many of the non-HLA genes, such as PTPN22 and CTLA-4, have been
      previously studied in MG and other autoimmune diseases and their association with
      MG has been reevaluated in more cohesive groups of patients. Moreover, novel risk
      or protective loci have been revealed, as in the case of TNIP1 and FOXP3.
      Although the majority of these results have been derived from candidate gene
      studies, the focal point of all recent genetic studies is the first genome-wide
      association study (GWAS) conducted on early-onset MG patients. 

PMID- 24294610
TI  - The effect of created local hyperosmotic microenvironment in microcapsule for the
      growth and metabolism of osmotolerant yeast Candida krusei.
AB  - Candida krusei is osmotolerant yeast used for the production of glycerol.
      Addition of osmolyte such as NaCl into culture medium can increase the production
      of glycerol from glucose, but osmolytes may burden the glycerol separation. A
      coencapsulation method was suggested to create local extracellular hyperosmotic
      stress for glycerol accumulation. Firstly, the influence of osmotic stress
      induced by the addition of PEG4000 on growth and metabolism of free cell was
      studied in detail. Glycerol accumulation could be improved by employing PEG4000
      as osmoregulator. Secondly, cells and PEG4000 were coentrapped in NaCS/PDMDAAC
      capsules to create local hyperosmotic stress. The effects of local hyperosmotic
      microenvironment on the cell growth and metabolism were studied. The coentrapment
      method increased the glycerol concentration by 25%, and the glycerol
      concentration attained 50 gL-1 with productivity of 18.8 gL-1Day-1 in shake
      flask. More importantly, the glycerol could be directly separated from the
      encapsulated cells. The entrapped cells containing PEG4000 were also cultivated
      for 15 days in an airlift reactor. The yield and productivity were ca. 35% and 21
      gL-1Day-1, respectively.

PMID- 24294608
TI  - Role of toll-interacting protein gene polymorphisms in leprosy Mexican patients.
AB  - BACKGROUND: Leprosy is a debilitating infectious disease of human skin and
      nerves. Genetics factors of the host play an important role in the disease
      susceptibility. Toll-interacting protein (TOLLIP) is an inhibitory adaptor
      protein within the toll-like receptor (TLR) pathway, which recognizes
      structurally conserved molecular patterns of microbial pathogens, initiating
      immune responses. The objective of this study was to investigate the association
      of variants in the TOLLIP gene with susceptibility to leprosy in Mexican
      patients. METHODS: TOLLIP polymorphisms were studied using a case-control design
      of Mexican patients with lepromatous leprosy (LL). The polymorphisms of TOLLIP at
      loci -526 C>G (rs5743854), 1309956C>T (rs3750920), 1298430C>A (rs5744015), and
      1292831 G>A (rs3750919) were analyzed by PCR, with sequence-specific primers in
      LL patients and healthy subjects (HS) as controls. RESULTS: Genotype
      distributions were in Hardy Weinberg equilibrium for all sites except for
      rs3750920. Neither genotype nor allele frequencies were statistically different
      between LL patients and controls (P > 0.05). The maximum pairwise D' coefficient
      reached was 0.44 of linkage (P = 0.01) for all the polymorphisms except for
      rs5743854. The three loci haplotype comparison yielded no significant differences
      between groups. CONCLUSIONS: Just the individuals with genotype C/C of rs3750920
      have a trend of protective effect to developing LL.

PMID- 24294612
TI  - From the patient's perspective.

PMID- 24294613
TI  - Selecting medical students who will become general practitioners: is the aptitude
      test suitable?

PMID- 24294611
TI  - Side population cells as prototype of chemoresistant, tumor-initiating cells.
AB  - Classically, isolation of CSCs from tumors exploits the detection of cell surface
      markers associated with normal stem cells. Invariable expression of these cell
      surface markers in almost all proliferating tumor cells that albeit impart
      specific functionality, the universality, and clinical credibility of CSC
      phenotype based on markers is still dubious. Side Population (SP) cells, as
      defined by Hoechst dye exclusion in flow cytometry, have been identified in many
      solid tumors and cell lines and the SP phenotype can be considered as an enriched
      source of stem cells as well as an alternative source for the isolation of cancer
      stem cells especially when molecular markers for stem cells are unknown. SP cells
      may be responsible for the maintenance and propagation of tumors and the
      proportion of SP cells may be a predictor of patient outcome. Several of these
      markers used in cell sorting have emerged as prognostic markers of disease
      progression though it is seen that the development of new CSC-targeted strategies
      is often hindered by poor understanding of their regulatory networks and
      functions. This review intends to appraise the experimental progress towards
      enhanced isolation and drug screening based on property of acquired
      chemoresistance of cancer stem cells. 

PMID- 24294614
TI  - Shaping the future medical workforce: take care with selection tools.
AB  - INTRODUCTION: Medical school selection is a first step in developing a general
      practice workforce. AIM: To determine the relationship between medical school
      selection scores and intention to pursue a career in general practice. METHODS: A
      longitudinal cohort study of students selected in 2006 and 2007 for The
      University of Auckland medical programme, who completed an exit survey on career
      intentions. Students are ranked for selection into year 2 of a six-year programme
      by combining grade point average from prior university achievement (60%),
      interview (25%) and Undergraduate Medicine and Health Sciences Admission Test
      (UMAT) scores (15%). The main outcome measure was level of interest in general
      practice at exit. Logistic regression assessed whether any demographic variables
      or admission scores predicted a 'strong' interest in general practice. RESULTS:
      None of interview scores, grade point average, age, gender, or entry pathway
      predicted a 'strong' interest in general practice. Only UMAT scores
      differentiated between those with a 'strong' interest versus those with 'some' or
      'no' interest, but in an inverse fashion. The best predictor of a 'strong'
      interest in general practice was a low UMAT score of between 45 and 55 on all
      three UMAT sections (OR 3.37, p=0.020). Yet, the academic scores at entry of
      students with these UMAT scores were not lower than those of their classmates.
      DISCUSSION: Setting inappropriately high cut-points for medical school selection
      may exclude applicants with a propensity for general practice. These findings
      support the use of a wider lens through which to view medical school selection
      tools.

PMID- 24294615
TI  - Sleep disorders among high school students in New Zealand.
AB  - INTRODUCTION: Adolescents are known to have high risk factors for sleep
      disorders, yet the youth rates of sleep disturbances are unknown. AIM: This study
      aimed to determine the prevalence of sleep disorders among New Zealand high
      school students. METHODS: The Auckland Sleep Questionnaire (ASQ) was administered
      to high school students at six schools in the North Island. Schools were chosen
      to reflect a range of ethnicities and school deciles, which identify the
      socioeconomic status of households in the school catchment area. RESULTS: A total
      of 1388 students completed the ASQ. The median age was 17 years (range 14-23) and
      females represented 43.5% (n=604) of the total group. A total of 37.2% of the
      students surveyed reported having significant sleep symptoms lasting longer than
      one month. Depression and anxiety were present in 51.7% and 44.8% of students
      reporting a sleep problem, respectively. A moderate correlation was observed
      between sleep problems and depression (r=0.34, p<0.01), and sleep problems and
      anxiety (r=0.31, p<0.01). Problem alcohol use and other substance use were more
      common in students with sleep symptoms (12.2% and 5.5% respectively). No
      difference was found in the rate of sleep problems reported by different ethnic
      groups. DISCUSSION: A considerable proportion of students surveyed reported
      significant sleep symptoms. This study has the potential to aid physicians within
      New Zealand in better appreciating the burden of sleep disorders faced by young
      people and in effectively assessing and managing different causes of sleep
      symptoms in this demographic.

PMID- 24294616
TI  - Staff views of an opportunistic chlamydia testing pilot in a primary health
      organisation.
AB  - INTRODUCTION: The Auckland chlamydia pilot was one of three pilots funded by the
      Ministry of Health to trial implementation of the 2008 Chlamydia Management
      Guidelines prior to national roll-out. AIM: To assess what elements in the
      testing programme pilot worked best for staff and to determine how an
      opportunistic testing programme could be better configured to meet staff needs
      and preferences. METHODS: A staff survey listed key chlamydia testing tasks in
      chronological order, and service interventions supporting these tasks. Staff were
      asked to rate each task on its difficulty prior to the pilot, and then on the
      difference the pilot had made to each task. They were also asked to rate service
      interventions on their usefulness during the pilot implementation. RESULTS: The
      survey had a response rate of 94%. The testing tasks posing the greatest
      difficulties to staff were those involving patient interactions (41%) and
      management of follow-up (52%). About 70% of staff felt tasks were improved by the
      pilot. Staff considered the three most useful service interventions to be a
      chlamydia-specific template created for the practice management system, provision
      of printed patient resources, and regular team discussions with other staff.
      DISCUSSION: A significant proportion of staff reported difficulties with routine
      tasks required for opportunistic testing for chlamydia, highlighting the need to
      involve staff during programme design. Practice nurse-led approaches to future
      opportunistic testing programmes should be considered as nurses had a more
      positive response to the pilot and nurse-led approaches have been shown to be
      successful overseas.

PMID- 24294617
TI  - The association between church attendance and obesity-related lifestyle
      behaviours among New Zealand adolescents from different Pacific Island ethnic
      groups.
AB  - INTRODUCTION: Obesity is disproportionately prevalent among Pacific population
      groups in New Zealand. Lifestyle behaviours of excessive consumption of high
      energy, unhealthy foods and inadequate physical activity are risk factors for
      obesity that can be modified. AIM: To identify and describe the risk factors for
      and protective factors against obesity among Pacific Island (PI) adolescents who
      attend church and compare them with PI adolescents who do not attend church.
      METHODS: We investigated the lifestyle behaviours of 2495 PI adolescents at six
      secondary schools in Auckland, New Zealand (NZ), 77% of whom attend a church or
      other place of worship. The cross-sectional survey was undertaken in 2005.
      Structured individual interviews and anthropometric measurements were undertaken.
      RESULTS: Church attendees had a higher mean body mass index (BMI) compared with
      non-attendees (BMI 27.4 vs BMI 26.6), adjusted for age, gender and PI ethnicity
      (p=0.01). The weight status of attendees was associated with less healthy
      breakfast and lunch sources, lower levels of physical activity, and limited
      knowledge of the risk factors for obesity (p<0.05) DISCUSSION: Culturally
      appropriate and ethnic-specific weight management interventions, including
      monitoring and policy development programmes, are needed urgently to change pro
      obesity lifestyle behaviours in PI adolescents and to avoid the burgeoning future
      obesity-related illnesses that would otherwise result. The church may be an
      important venue and change agent in the prevention of obesity for this
      population.

PMID- 24294618
TI  - Patients' perceptions of their general practitioner's health and weight
      influences their perceptions of nutrition and exercise advice received.
AB  - INTRODUCTION: General practitioners (GPs) play an important role in the
      management of patients who are overweight or obese. Previous research suggests
      that GPs' physical characteristics may influence patients' perceptions of health
      care received during consultations, mediating the likelihood of patients
      following health advice provided by GPs. This study aimed to explore patients'
      perceptions of their GP's health status and its influence on patients'
      perceptions of healthy eating and exercise advice. METHODS: An interpretive
      approach to phenomenology underpinned the qualitative inquiry and study design.
      Twenty-one participants (aged 55.9 +/- 6.5 years; 14 females, 7 males) who had
      previously received healthy eating and/or exercise advice from a GP participated
      in an individual semi-structured interview. A constant comparison approach to
      thematic analysis was conducted. FINDINGS: Participants identified three key
      indicators of perceived health of their GP. These included the GP's physical
      appearance, particularly weight status; perceived absence of ill health; and
      disclosure of a GP's health behaviours. Participants expressed favourable
      perceptions of the weight status of their GP. Participants expected their GP to
      be a healthy role model and often, but not always, felt more confident receiving
      advice from a GP that they perceived as healthy. CONCLUSION: The findings
      highlight that a GP's perceived health status influences patients' perceptions of
      the health advice received during consultations. These findings provide a
      foundation for future research that may allow GPs to modify patients' perceptions
      of their health status in order to facilitate behaviour change in overweight or
      obese patients.

PMID- 24294619
TI  - 'It's whanaungatanga and all that kind of stuff': Maori cancer patients'
      experiences of health services.
AB  - INTRODUCTION: There are unacceptable ethnic differences in cancer survival in
      Aotearoa/New Zealand. For people with cancer, quality of life and survival are
      shaped by access to care, but research on Maori access to, and through, cancer
      care is limited. Internationally, research has shown that primary care plays an
      important role in providing patient-centred, holistic care and information
      throughout the cancer care journey. Additionally, Maori health providers provide
      practical support and facilitate access to all levels of health care. Here we
      describe the cancer journeys of Maori patients and whanau and identify factors
      that may facilitate or inhibit access to and through cancer care services.
      METHODS: Twelve Maori patients affected by cancer and their whanau (family) in
      the lower North Island took part in face-to-face semi-structured interviews
      exploring their experiences of cancer screening, diagnosis, treatment, survival
      and palliative care. FINDINGS: Three key areas were identified that impacted upon
      the cancer care journey: the experience of support; continuity of care; and the
      impact of financial and geographic determinants. CONCLUSION: Primary care plays a
      key role in support and continuity of care across the cancer journey. Alongside
      interpersonal rapport, a long-term relationship with a primary health provider
      facilitated a more positive experience of the cancer care journey, suggesting
      that patients with a 'medical home' are happier with their care and report less
      problems with coordination between services. Positive, longstanding relationships
      with general practitioners and Maori health providers assisted patients and
      whanau with the provision and understanding of information, alongside practical
      support.

PMID- 24294620
TI  - Barriers to Maori sole mothers' primary health care access.
AB  - INTRODUCTION: International research consistently shows that sole mothers
      experience poorer health and suboptimal health care access. New Zealand studies
      on sole mothers' health report similar findings. The aim of this exploratory
      research was to better understand the experiences of Maori sole mothers' access
      to health services, particularly primary health care, for personal health needs.
      METHODS: This qualitative study employed a general inductive design informed by a
      Kaupapa Maori approach, providing guidance on appropriate cultural protocols for
      recruiting and engaging Maori participants. Distributing written information and
      snowballing techniques were used to purposively recruit seven Maori sole mothers.
      Data collection involved semi-structured interviews which were digitally recorded
      and transcribed verbatim. Data were analysed using general inductive thematic
      analysis to identify commonalities and patterns in participants' experiences.
      FINDINGS: The dominant themes that emerged captured and described participants'
      experiences in accessing health care. The major barrier to access reported was
      cost. Compounding cost, transport difficulties and location or scheduling of
      services were additional barriers to health service accessibility. Child-related
      issues also posed a barrier, including prioritising children's needs and
      childcare over personal health needs. CONCLUSION: The findings illuminate Maori
      sole mothers' experiences of accessing health care and the complex socioeconomic
      inequalities affecting access options and uptake of services. Further
      investigation of barriers to access is needed. The study has implications for
      addressing barriers to access at policy, funding and practice levels to improve
      health outcomes and equitable health care access for Maori sole mothers.

PMID- 24294621
TI  - Implementing a Continuity of Cancer Care nursing role into a New Zealand primary
      health organisation - the patient's perspective.
AB  - INTRODUCTION: A Continuity of Cancer Care pilot project was established in two
      urban general practices, with the goal of improving cancer care and patient
      access to services. Practice nurses were engaged as coordinators to implement a
      model of care and patient navigation to offer continued and consistent care, and
      to assist the patient to navigate their cancer experience. AIM: The aim was to
      evaluate the effectiveness of the Continuity of Cancer Care pilot project.
      METHODS: Patients enrolled in the pilot project were invited to participate. Each
      participant completed a Patient Satisfaction Questionnaire and SF-12 Health
      Survey, and was then invited to take part in an interview. The evaluation
      framework utilised concepts of informational, management and relational
      continuity. RESULTS: The SF-12 subcategories of physical functioning, role
      physical, bodily pain and role emotional were lower than other results from
      cancer patients in the literature. The Patient Satisfaction Questionnaire and
      interviews indicated patients were satisfied with the relational continuity
      components of the project, but that gaps existed within the management and
      informational continuity aspects of care. DISCUSSION: Overall, the participants
      were satisfied with the Continuity of Cancer Care programme and valued the
      support, clarification and listening aspects of the programme. However, when
      evaluated in relation to a more comprehensive definition of continuity of care,
      there were distinct gaps. While the relational aspects of continuity of care were
      mostly achieved, the management and informational aspects appeared to be limited
      primarily to nurses acting to interpret hospital and general practitioner
      comments for patients.

PMID- 24294622
TI  - New Zealand drinking water should be fluoridated: yes.

PMID- 24294623
TI  - New Zealand drinking water should be fluoridated: no.

PMID- 24294624
TI  - Responding to cellulitis in Pacific communities.

PMID- 24294625
TI  - Dynamic consent in the digital age of biology: online initiatives and regulatory
      considerations.

PMID- 24294626
TI  - Interprofessional education in our universities will ultimately bring better
      health outcomes to our patients.

PMID- 24294627
TI  - Response to medicines adherence: evidence for any intervention is disappointing.

PMID- 24294628
TI  - Screening of serine protease inhibitors with antimicrobial activity using iron
      oxide nanoparticles functionalized with dextran conjugated trypsin and in silico
      analyses of bacterial serine protease inhibition.
AB  - Plants produce a variety of proteins and peptides which are involved in their
      defense against pathogens. Serine protease inhibitors are a well-established
      class of inhibitors correlated with plant defense. Increased levels of protease
      inhibitors delay cell damage and expand the cell's life-span. Recently, the rapid
      emergence of antibiotic-resistant microbial pathogens has prompted immense
      interest in purifying novel antimicrobial proteins or peptides from plant
      sources. Usually, the purification of protease inhibitors is accomplished by salt
      extraction, ultrafiltration and affinity chromatography. Here, we developed a
      novel approach based on iron oxide nanoparticles conjugated to dextran
      functionalized with trypsin beads that accelerate the quick screening and
      purification of antimicrobial peptides with serine protease inhibitor activity.
      The method described here also works for screening other inhibitors using
      particular protein kinases, and it is therefore a novel tool for use as the
      leading method in the development of novel antimicrobial agents with protease
      inhibitory activity. Finally, and no less important, molecular modelling and
      dynamics studies of a homologous inhibitor studied here with Escherichia coli
      trypsin and chymotrypsin are provided in order to shed some light on inhibitor
      enzyme interactions. 

PMID- 24294629
TI  - Are you ready for the sheriff?

PMID- 24294630
TI  - Preparing for new dental legislation.

PMID- 24294631
TI  - A cosmos of particles. Neutninos from deep space are up a new kind of astronomy.

PMID- 24294632
TI  - Steer clear: turtles ultraviolet LEDs help sea turtles avoid deadly encounters
      with fishing nets.

PMID- 24294633
TI  - Why so jittery? More and more products contain more and more caffeine.

PMID- 24294634
TI  - Copayment for extended care services. Final rule.
AB  - This document promulgates Department of Veterans Affairs (VA) final regulations
      amending the definition of "spousal resource protection amount'' to reference the
      Maximum Community Spouse Resource Standard, which is adjusted and published each
      year by the Centers for Medicare and Medicaid Services (CMS). This change has the
      immediate effect of increasing the spousal resource protection amount from
      $89,280 to $115,920, and ensures that the spousal resource protection amount will
      stay consistent with the comparable protection for the spouses of Medicaid
      recipients.

PMID- 24294635
TI  - Medicare and Medicaid programs; Home Health Prospective Payment System rate
      update for CY 2014, home health quality reporting requirements, and cost
      allocation of home health survey expenses. Final rule.
AB  - This final rule will update the Home Health Prospective Payment System (HH PPS)
      rates, including the national, standardized 60-day episode payment rates, the
      national per-visit rates, the low-utilization payment adjustment (LUPA) add-on,
      and the non-routine medical supply (NRS) conversion factor under the Medicare
      prospective payment system for home health agencies (HHAs), effective January 1,
      2014. As required by the Affordable Care Act, this rule establishes rebasing
      adjustments, with a 4-year phase-in, to the national, standardized 60-day episode
      payment rates; the national per-visit rates; and the NRS conversion factor. In
      addition, this final rule will remove 170 diagnosis codes from assignment to
      diagnosis groups within the HH PPS Grouper, effective January 1, 2014. Finally,
      this rule will establish home health quality reporting requirements for CY 2014
      payment and subsequent years and will clarify that a state Medicaid program must
      provide that, in certifying HHAs, the state's designated survey agency carry out
      certain other responsibilities that already apply to surveys of nursing
      facilities and Intermediate Care Facilities for Individuals with Intellectual
      Disabilities (ICF-IID), including sharing in the cost of HHA surveys. For that
      portion of costs attributable to Medicare and Medicaid, we will assign 50 percent
      to Medicare and 50 percent to Medicaid, the standard method that CMS and states
      use in the allocation of expenses related to surveys of nursing homes.

PMID- 24294636
TI  - Medicare program; end-stage renal disease prospective payment system, quality
      incentive program, and durable medical equipment, prosthetics, orthotics, and
      supplies.
AB  - This rule updates and makes revisions to the End-Stage Renal Disease (ESRD)
      prospective payment system (PPS) for calendar year (CY) 2014. This rule also sets
      forth requirements for the ESRD quality incentive program (QIP), including for
      payment year (PY) 2016 and beyond. In addition, this rule clarifies the
      grandfathering provision related to the 3-year minimum lifetime requirement (MLR)
      for Durable Medical Equipment (DME), and provides clarification of the definition
      of routinely purchased DME. This rule also implements budget-neutral fee
      schedules for splints and casts, and intraocular lenses (IOLs) inserted in a
      physician's office. Finally, this rule makes a few technical amendments and
      corrections to existing regulations related to payment for durable medical
      equipment, prosthetics, orthotics, and supplies (DMEPOS) items and services.

PMID- 24294637
TI  - Schedules of controlled substances: placement of perampanel into Schedule III.
      Final rule.
AB  - With the issuance of this final rule, the Deputy Administrator of the Drug
      Enforcement Administration (DEA) places the substance perampanel [2-(2-oxo-1
      phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile], including its
      salts, isomers, and salts of isomers, into schedule III of the Controlled
      Substances Act (CSA). This scheduling action is pursuant to the CSA which
      requires that such actions be made on the record after opportunity for a hearing
      through formal rulemaking. This action imposes the regulatory controls and
      administrative, civil, and criminal sanctions applicable to schedule III
      controlled substances on persons who handle (manufacture, distribute, dispense,
      import, export, engage in research, conduct instructional activities with, or
      possess) or propose to handle perampanel.

PMID- 24294638
TI  - [Abstracts of the 101st Annual Meeting of the Japanese Urological Association.
      April 25-28, 2013. Sapporo, Japan].

PMID- 24294639
TI  - [Abstracts of the 55th Annual Meeting of the Japanese Society of Child Neurology.
      May 30-June 1, 2013. Oita, Japan].

PMID- 24294640
TI  - [The 110th meeting of the Japanese Society of Internal Medicine. Tokyo, Japan.
      April 12-14, 2013. Abstracts].

PMID- 24294641
TI  - [Abstracts of the 25th Spring Meeting of the Japanese Society of Allergology. May
      11-12, 2013, Yokohama, Japan].

PMID- 24294642
TI  - Re: Noninvasive methods to evaluate bladder obstruction in men.

PMID- 24294643
TI  - Reply by the authors.

PMID- 24294644
TI  - Methods, measures, and metrics of nurse staffing: uncovering the evidence.

PMID- 24294645
TI  - Staffing excellence in the decade of disruptive innovation in health care.

PMID- 24294646
TI  - The impact of research on staffing: an interview with Linden Aiken--Part 1.
      Interview by Karlene M Kerfoot and Kathy S Douglas.

PMID- 24294647
TI  - Nurse staffing: the Illinois experience.
AB  - In March of 2008 the final rules for Illinois' Nurse Staffing by Patient Acuity
      Act were published. This law represents the collaborative efforts of the Illinois
      Nurses Association and the Illinois Hospital Association in authoring legislation
      which is an alternative to mandated staffing ratios and provides nurses a voice
      in their organization's staffing plan. The rules are not prescriptive and
      therefore each organization has significant latitude in operationalizing the
      requirements. Best practices from across the state were identified and
      communicated to nurse leaders through a variety of mechanisms. The Illinois
      experience can serve as an exemplar for other states as nursing leaders debate
      the question of nurse staffing with legislators.

PMID- 24294648
TI  - Building effective workforce management practices through shared governance and
      technology systems integration.
AB  - In integrated delivery networks (IDNs) with complex management structures, shared
      governance in nursing is a proven model for health care delivery. After Advocate
      Health Care, the largest IDN in Illinois, implemented shared governance in its
      nursing, clinical, and non-clinical departments and restructured the
      organization's technology use, it benefited greatly from a new, shared decision
      making process. After listening to business consultants, clinical professionals,
      and information technology experts, hospitals should take the blended, or
      comprehensive, approach to new projects. They can succeed by promoting
      communication supported by an integrated computer platform that helps nursing and
      business executives reach a consensus. Traditional modes of operation, in which
      individual administrative, clinical, and technology departments separately
      introduce innovation, do not deliver an advantage. However, models that
      incorporate open communication, integration, and knowledge sharing will help
      large IDNs and other complex health care organizations make the best possible use
      of their resources and investments.

PMID- 24294649
TI  - What is driving the growing demand for consulting in hospital staffing,
      scheduling, and productivity?
AB  - Productivity improvement has been influenced by crises such as the initiation of
      diagnosis-related groups, the Balanced Budget Act, and now health care reform. A
      key element in successfully improving labor efficiency and productivity lies in
      developing relationships inside the organization. Essential to productivity
      improvement work is accurate, reliable information. Collaborating across
      departments and disciplines can greatly enhance the productivity efforts of
      staff. It is important to remember culture of the organization often drives the
      best approach and determines if the changes are sustainable. Only through deep
      learning and listening can the consultant or leader design the approach that will
      be successful for a given organization.

PMID- 24294650
TI  - Measuring nursing unit environments with four composite measure.
AB  - Understanding the context in which nurses work is an important step to designing
      work environments in which nurses can achieve targeted quality. Developing a
      usable instrument for describing the work environment and the relationship to
      staffing is essential for the development of evidence-based staffing decisions.
      The major implications of the research reported here are that the work
      environment of nurses, while complex, can be modeled with composite variables
      that reflect various dimensions of that environment. This ability to model the
      environment with fewer variables enhances the interpretation of environmental
      factors that have the greatest impact on patient outcomes. This reduction is
      valuable to the clinician, manager, and administrator in determining the key
      factors that need to be altered in the work environment to improve the quality of
      the patient experience.

PMID- 24294651
TI  - Nursing's role and staffing in accountable care.
AB  - Nurse staffing in a world of health care reform and accountable care is uncertain
      and creates fear not only for the nurse leaders, but all RNs. As health care
      reform transforms the environment, so must the role and staffing of nurses. There
      is still not one right answer or agreed upon manner to nurse staffing of
      inpatient units. This leaves nurses free to imagine roles and staffing
      possibilities for the future across the continuum. Including all RNs in
      conversations, visioning, and problem solving for the future will best prepare
      the profession for our role in caring for our patients.

PMID- 24294652
TI  - Historical data indicates a wage premium for black registered nurses.
AB  - The average observed wage of Black registered nurses (RNs) is higher than that of
      White RNs in the National Sample Survey of Registered Nurses over 2 decades from
      1984 to 2004. In this study, wages of Black and White RNs were analyzed
      controlling for factors likely to affect wages in addition to race. Results
      indicate racial inequality in wages of RNs: Black RN wages exceeded White RNs
      wages over 2 decades from 1984-2004. This significant difference remained after
      controlling for factors likely to affect wages in addition to race such as
      experience, education, employer type, and specialty among other factors.

PMID- 24294653
TI  - [Palliative sedation can not be ordered].

PMID- 24294654
TI  - [2013 Nobel Prize in Physiology or Medicine. The Nobel laureates have explored a
      complicated transport system].

PMID- 24294655
TI  - [Severe TBE with sequelae can also affect young children. Vaccination advice to
      children should be individualized, degree of exposure essential].

PMID- 24294656
TI  - [Methylene blue stopped metformin-associated lactic acidosis and refractory
      vasodilatation].

PMID- 24294657
TI  - [Updated management of adults with head injuries. Scandinavian Neurotrauma
      Committee's new guidelines provide guidance at minimal, mild and moderate
      injuries].

PMID- 24294658
TI  - [Paracetamol poisoning is getting more and more common. The Swedish Poison
      Information Centre raise the alarm--time for countermeasures].

PMID- 24294659
TI  - [Close monitoring is required when adrenaline is administered in combination with
      tricyclic antidepressive agents].

PMID- 24294660
TI  - [More kidney transplantations with matching mechanism].

PMID- 24294661
TI  - [Palliative care is life-help, not euthanasia].

PMID- 24294662
TI  - [Treatment of mental health problems needs to be evaluated].

PMID- 24294663
TI  - [Wind power noise is not an infrasound problem].

PMID- 24294664
TI  - [Medline--a treasure trove for physicians and researchers. How the database with
      over 20 million medical references was created].

PMID- 24294665
TI  - Sentinel event statistics for first half of 2013.

PMID- 24294666
TI  - New Speak Up video addresses medical care in the home.

PMID- 24294667
TI  - E-SOC gets a facelift. Small changes enhance user experience.

PMID- 24294668
TI  - Joint Commission and AMA-convened PCPI recommend strategies to minimize overuse.

PMID- 24294669
TI  - Stable pattern marks this year's salary survey, but retirement looms.

PMID- 24294670
TI  - Surgical liaisons: the bridge between the OR and family members.

PMID- 24294671
TI  - Robotic surgery complications underreported.

PMID- 24294672
TI  - Increased patient safety, cost savings head list of overall accomplishments.

PMID- 24294673
TI  - Comprehensive dashboards paint a fuller picture of OR performance.

PMID- 24294674
TI  - Survey suggests signs of improvement in ASC environment.

PMID- 24294675
TI  - Editorial: Embedding systems-level quality improvement for dissemination and
      sustainability across many practices and conditions.

PMID- 24294676
TI  - Complete care at Kaiser Permanente: transforming chronic and preventive care.
AB  - BACKGROUND: In 2004 Kaiser Permanente Southern California (KPSC) recognized the
      potential to improve the quality of care. Healthcare Effectiveness Data and
      Information Set (HEDIS) performance was below what regional leadership aspired to
      achieve, exceeding the 90th national percentile on only 15 of 34 measures.
      Beginning in 2005 regional leadership identified several system opportunities to
      enhance evidence-based, person-focused care. DEVELOPMENT OF COMPLETE CARE: KPSC
      developed and implemented a comprehensive delivery system redesign and expanded
      and integrated existing clinical information systems, decision support, work
      flows, and self-management support-collectively referred to as Complete Care. The
      goal of Complete Care is to transform care for healthy members, those with
      chronic conditions, and those with multiple comorbidities. To date, KPSC has
      applied Complete Care to 26 chronic conditions and areas of preventive and
      wellness care. Implemented in all care settings and optimizing the roles of all
      health care team members to maximal scope of practice, Complete Care provides
      evidence-based, person-focused care addressing a large set of protocol-based
      health needs for every individual during every encounter within the health care
      system. RESULTS: On 51 HEDIS metrics, KPSC improvement using Complete Care
      averaged 13.0%, compared with 5.5% improvement in the national HEDIS 50th
      percentile. CONCLUSION: Implementation of Complete Care at KPSC was followed by
      six-year quality gains that outpaced changes in the HEDIS national percentiles
      for many measures. Additional care gaps have been included in proactive office
      encounter checklists; these relate to elder care, advance directives,
      posthospital care, immunizations, health maintenance, and pregnancy care.

PMID- 24294677
TI  - Evaluation of a problem-specific SBAR tool to improve after-hours nurse-physician
      phone communication: a randomized trial.
AB  - BACKGROUND: After-hours telephone communications are common in patient
      management. Patterns of communication of key information during after-hours phone
      calls were evaluated, and the utility of problem-specific Situation, Background,
      Assessment, Recommendation (SBAR) forms in improving this communication was
      assessed. METHODS: In a randomized trial using a simulated on-call setting, 20
      nurses called physicians regarding six cases adapted from inpatient records and
      based on the six most common reasons for after-hours nurse-physician
      communication. Three of the cases were handled without the SBAR forms (control
      cases), and three cases were handled with the forms (SBAR cases). Two cue types
      of communication were evaluated: situation cues, which conveyed the patient's
      situation (for example, a patient is confused), and background cues, which
      conveyed problem-specific data indicated on the SBAR forms (for example, the
      patient has a low sodium level). RESULTS: Ninety-two phone calls were analyzed
      (43 SBAR/49 controls). Most of the nurses reported the situation cues (SBAR 88%,
      control 84%, p = .60) but not the background cues. There was a trend toward fewer
      background cues communicated in the SBAR cases (14% versus 31%, p = .08). In 14%
      of the cases, on average, nurses omitted information or reported wrong
      information regarding the background cue. Physicians asked questions that
      resulted in the communication of the cues in a minority of the cases when the
      background cues were not originally provided by the nurses (SBAR 6%, control 16%,
      p = .39). CONCLUSIONS: In after-hours phone communication between physicians and
      nurses, significant information was often not communicated and physicians did not
      elicit the necessary information. Simply providing an SBAR-based form did not
      ensure complete communication of key information.

PMID- 24294678
TI  - Development of an instrument to evaluate residents' confidence in quality
      improvement.
AB  - BACKGROUND: Practice-based learning and improvement is a core competency that all
      medical residents must demonstrate. Because confidence is important in
      translating competence into action, effective quality improvement (QI) curricula
      should evaluate trainees' knowledge and confidence to perform QI. Past efforts to
      assess educational outcomes in QI have not adequately evaluated trainees'
      confidence from a multidimensional perspective. METHODS: Participants--732
      internal medicine and family medicine residents from 42 training programs in the
      United States--completed the 31-item Quality Improvement Confidence Instrument
      (QICI), which was developed to measure confidence in six QI skill domains based
      on the Institute for Healthcare Improvement model ofQI. Confirmatory factor
      analysis was performed to support construct validity. Multivariate analysis of
      covariance was used to examine associations between residents' QI experience and
      other characteristics with confidence scores. RESULTS: Confirmatory factor
      analysis supported the QICI's multidimensional structure. Individual items
      yielded adequate variability, and reliability estimates for all six domains were
      high (> 0.86). On average, residents rated their confidence lowest for skills
      pertaining to choosing a target for improvement (specifically, using methods to
      evaluate interventions and to identify sources of process errors) and for testing
      a change in practice using specific tools for data collection and analysis. After
      controlling for program year and other characteristics, residents with previous
      QI experience reported significantly greater QI confidence. CONCLUSION: The QICI
      offers a psychometrically rigorous approach to evaluating residents' confidence
      levels. It can be used to gauge the appropriateness of a trainee's confidence
      against actual QI performance.

PMID- 24294679
TI  - A risk analysis of cancer care in Norway: the top 16 patient safety hazards.
AB  - BACKGROUND: Cancer care processes represents a number of potential threats to
      patient safety. A national risk analysis of Norwegian cancer care, entailing
      diagnosis, treatment, follow-up, palliative care, and terminal care, was
      conducted. METHODS: Literature review and a retrospective analysis of hazards in
      different national databases were combined with interviews with key health
      personnel in an attempt to identify 50 possible hazards. A project team from the
      Norwegian Board of Health Supervision (NBHS) and 23 other persons participated in
      the workshop in 2009. RESULTS: In a stepwise, consensus-driven process, the 23
      participants discussed the 50 possible hazards and then selected the 16 that they
      considered most important-clustered into three groups: diagnosis and primary
      treatment, interactions, and complications. The NBHS distributed the risk
      analysis report to a variety of stakeholders and asked Norway's hospital trusts
      to address the hazards. The report generally met a positive reception, albeit
      with local and interdisciplinary differences in the extent of the perceived
      applicability of the respective hazards. Two follow-up studies in 2012 and 2013
      showed that the hospital trusts lacked the implementation capacity to identify
      operational solutions to reduce the hazards. At the largest hospital trust in
      Norway-Oslo University Hospital-the Department of Oncology retested the national
      risk analysis in in 2011. Four groups, representing different parts of the
      patient care process. selected 9 of the 16 national hazards and identified 4 new
      ones. The department has established goals and appropriate activities for 3 of
      the hazards. CONCLUSIONS: The Ministry of Health and Care determined that
      hospital trusts must increase their implementation capacity regarding operational
      solutions to reduce the hazards.

PMID- 24294680
TI  - An initiative to improve the management of clinically significant test results in
      a large health care network.
AB  - BACKGROUND: The failure of providers to communicate and follow up clinically
      significant test results (CSTR) is an important threat to patient safety. The
      Massachusetts Coalition for the Prevention of Medical Errors has endorsed the
      creation of systems to ensure that results can be received and acknowledged.
      METHODS: In 2008 a task force was convened that represented clinicians,
      laboratories, radiology, patient safety, risk management, and information systems
      in a large health care network with the goals of providing recommendations and a
      road map for improvement in the management of CSTR and of implementing this
      improvement plan during the sub-force sequent five years. In drafting its
      charter, the task broadened the scope from "critical" results to "clinically
      significant" ones; clinically significant was defined as any result that requires
      further clinical action to avoid morbidity or mortality, regardless of the
      urgency of that action. RESULTS: The task force recommended four key areas for
      improvement--(1) standardization of policies and definitions, (2) robust
      identification of the patient's care team, (3) enhanced results
      management/tracking systems, and (4) centralized quality reporting and metrics.
      The task force faced many challenges in implementing these recommendations,
      including disagreements on definitions of CSTR and on who should have
      responsibility for CSTR, changes to established work flows, limitations of
      resources and of existing information systems, and definition of metrics.
      CONCLUSIONS: This large-scale effort to improve the communication and follow-up
      of CSTR in a health care network continues with ongoing work to address
      implementation challenges, refine policies, prepare for a new clinical
      information system platform, and identify new ways to measure the extent of this
      important safety problem.

PMID- 24294681
TI  - Congenital nasal pyriform aperture stenosis: conservative management.
AB  - OBJECTIVES: This case series outlines the advantages of using 0.1% intranasal
      dexamethasone drops (IDD) to treat nasal obstruction in patients with congenital
      pyriform aperture stenosis (PAS). METHODS: Five consecutive cases of PAS were
      reviewed. RESULTS: Three patients were treated with IDD alone, and 2 were treated
      surgically and had residual postoperative nasal obstruction before IDD. Four
      patients in follow-up (mean, 1 year) were weaned off the steroid drops with good
      breathing results. One patient developed iatrogenic Cushing's disease, and
      another, who was initially treated with surgery, eventually required nasal
      vestibular stenosis repair in addition to IDD. CONCLUSIONS: This study is the
      first to review the use of IDD in treating PAS. The potential impact of midnasal
      stenosis is discussed, and a conservative management algorithm for patients with
      PAS is presented. Careful surveillance for potential side effects of IDD is
      recommended, especially in cases that require elevated doses.

PMID- 24294682
TI  - Auditory brainstem implantation after unsuccessful cochlear implantation of
      children with clinical diagnosis of cochlear nerve deficiency.
AB  - OBJECTIVES: We compared the perceptual auditory abilities of 21 children with
      suspected cochlear nerve deficiency (CND) and a surgically verified absent
      cochlear nerve (CN) who first underwent cochlear implantation (CI) and
      subsequently underwent auditory brainstem implantation (ABI). METHODS: In this
      retrospective cohort study, from 2000 to 2011, 21 children initially underwent CI
      at an outside institution and failed to progress in their perceptual auditory
      abilities. Before CI, all of the children had severe to profound sensorineural
      hearing loss and a diagnosis of CND. Magnetic resonance imaging (MRI) documented
      an absent CN in 13 children and a small CN in 8 children. We performed
      explantation of the cochlear implant and simultaneous ABI on the same side. We
      performed MRI if no previous MRI results were available. All surgical videos were
      reviewed to determine the presence or absence of the CN. Measures of the
      patients' perceptual auditory abilities obtained after CI and after ABI were
      converted to the Category of Auditory Performance (CAP) scale. RESULTS: At
      surgery, all patients demonstrated an absent CN. After CI, all patients had a CAP
      score of 2 or less (mean, 0.52 +/- 0.68). After ABI, all patients had a CAP score
      of 2 or more (mean, 4.33 +/- 1.68); the improvement was statistically significant
      (p < 0.001). The complication rates were similar for CI and ABI. CONCLUSIONS: In
      this cohort of patients who had poor performance after CI, ABI achieved
      significantly improved performance as measured by the CAP and was shown to
      successfully rehabilitate hearing. Cases of a small CN may in reality represent
      an absent CN. Although this cohort was selected from patients with failed CI, the
      results have implications for the selection of device for patients with CND, in
      that ABI is a potential alternative to CI in select cases. In patients who fail
      to progress with intensive rehabilitation with CI or who have no progression in
      evoked auditory brainstem response, ABI must be considered early.

PMID- 24294683
TI  - Mastoid surgery under local anesthesia for medically unfit patients: techniques
      and outcome.
AB  - OBJECTIVES: We present the surgical techniques and outcomes of mastoid surgery
      under local anesthesia in patients who were unfit for general anesthesia.
      METHODS: Five tertiary-referred patients with multiple comorbidities and failed
      conservative treatment for chronic otitis media were operated on under local
      anesthesia. No sedation was administered. The principles of cholesteatoma surgery
      were observed, but the technique was adapted to keep surgical time to a minimum.
      RESULTS: None of the patients had perioperative problems, and all have dry,
      waterproof ears with preservation of hearing after surgery. So far, none of the
      patients have had recurrent or residual disease. CONCLUSIONS: Cholesteatoma
      surgery can be successfully performed with a local anesthetic in patients who are
      medically unfit for general anesthesia. Surgery requires a good coordination of
      the operating team in order to shorten the operating time. Otologists should
      develop and maintain their skills by performing ear surgery with local anesthetic
      on a regular basis.

PMID- 24294684
TI  - Antisecretory factor-inducing therapy improves patient-reported functional levels
      in Meniere's disease.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of specially
      processed cereal (SPC) as a suitable adjunctive treatment for Meniere's disease.
      METHODS: We performed a randomized double-blinded, placebo-controlled, crossover
      study in a tertiary referral center of patients who had a diagnosis of Meniere's
      disease based on the guidelines of the Committee on Hearing and Equilibrium of
      the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). The main
      outcome measure was the AAO-HNS Functional Level Scale (FLS). RESULTS: Thirty
      nine patients completed the study without any reported complications. The mean
      pretreatment FLS score for the entire study cohort was 3.8 (median, 4; range, 1
      to 6). The overall FLS score improved significantly (p < 0.001), to 2.8 (median,
      3), after SPC treatment. No patients showed worsening on the FLS during SPC or
      placebo treatment. Of the 39 patients, 23 showed improvement on the FLS, and no
      change was observed in the remaining 16. The median improvement on the FLS in
      these 23 patients was 2 points (mean, 1.7; range, 1 to 4). The mean FLS score
      after placebo cereal treatment was not significantly different from baseline (p =
      0.452), but was significantly higher than that after SPC treatment (mean, 3.7; p
      < 0.001). The marginal difference observed between the baseline FLS score and the
      placebo FLS score was due to the fact that 5 patients reported 1-point
      improvements on the FLS after placebo treatment. Nevertheless, significantly
      fewer patients improved on placebo than on SPC (p < 0.001). CONCLUSIONS:
      Treatment with SPC appears to be well tolerated by most patients (91%) without
      any complications. More than half (59%) of the study cohort reported subjective
      improvement in functional level.

PMID- 24294685
TI  - Multislice computed tomography overestimates superior semicircular canal
      dehiscence syndrome.
AB  - OBJECTIVES: We assessed the prevalence of superior semicircular canal dehiscence
      (SSCD) through examination of ultrahigh-resolution computed tomography (CT) scans
      of the temporal bone and attempted to verify the correspondence between a
      radiologic diagnosis of SSCD and clinical signs of SSCD syndrome. METHODS: A
      prospective study was carried out on 191 consecutive patients who underwent
      temporal bone ultrahigh-resolution CT scans. Cases that matched the radiologic
      diagnosis of SSCD were subsequently referred for a comprehensive audiological
      evaluation that might enable a final diagnosis of SSCD syndrome. RESULTS: Among
      the 191 patients, 17 had a radiologic diagnosis of SSCD, which was bilateral in 5
      cases, for a total of 22 SSCD cases, with a prevalence rate of 5.8%. In 2 of the
      17 patients, the audiological examination revealed signs and symptoms indicative
      of SSCD syndrome, with a total prevalence rate of 0.5%. CONCLUSIONS: Our data
      confirm that the radiologic diagnosis of SSCD, performed by mean thin-section CT
      scans reformatted in the plane of the superior semicircular canal, is not
      necessarily related to the clinical presentation of SSCD syndrome. Our study also
      showed a prevalence rate of SSCD syndrome that was similar to the prevalence of
      SSCD reported from studies of histologic specimens.

PMID- 24294686
TI  - Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic
      changes in airway epithelial cells.
AB  - OBJECTIVES: Laryngopharyngeal reflux (LPR) is associated with inflammatory and
      neoplastic airway diseases. Gastric pepsin internalized by airway epithelial
      cells during reflux contributes to oxidative stress, inflammation, and
      carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes
      and inflammatory or neoplastic changes to the esophagus in models of
      gastroesophageal reflux. This study examined the potential of chemoprotective
      phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of
      airway epithelial cells. METHODS: Cultured human laryngeal and hypopharyngeal
      epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium
      (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL)
      30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were
      treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and
      proliferative changes were assessed by electron microscopy, cell count, thymidine
      analog incorporation, and real-time polymerase chain reaction array. Pepsin
      inhibition was determined by in vitro kinetic assay. RESULTS: Micromolar
      concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited
      peptic activity and pepsin-induced mitochondrial damage and hyperproliferation.
      Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression
      and altered the subcellular localization of pepsin following endocytosis.
      CONCLUSIONS: Several phytochemicals inhibit the pepsin-mediated cell damage
      underlying inflammatory or neoplastic manifestations of LPR. Dietary
      supplementation or adjunctive therapy with phytochemicals may represent novel
      preventive or therapeutic strategies for LPR-attributed disease.

PMID- 24294687
TI  - Postoperative nasal debridement after endoscopic sinus surgery: a randomized
      controlled trial.
AB  - OBJECTIVES: Postoperative debridement is a controversial subject in the rhinology
      literature. The objective of this randomized controlled trial was to determine
      the effect of regular debridement versus no debridement on disease-specific
      outcomes and patient inconvenience. METHODS: Patients with chronic rhinosinusitis
      with polyposis who were to undergo basic sinus surgery (antrostomy,
      ethmoidectomy, and polypectomy) were randomized to either debridement (at
      postoperative weeks 2 and 4) or no debridement, and their outcomes were assessed
      at 4 weeks and at 6 months with the Lund-Kennedy Endoscopic Score (LKES), the
      Sino-Nasal Outcome Test-21 (SNOT-21), a visual analog scale for postoperative
      pain, and a novel scoring system for postoperative inconvenience (Post-Operative
      Inconvenience Scale; POIS). All patients were instructed to use high-volume
      saline rinses twice daily. RESULTS: At 4 weeks after operation, there was no
      difference between the groups in regard to LKESs (control group, 2.1 of 20;
      debridement group, 2.4 of 20; p = 0.59) or SNOT scores (control group, 9.1;
      debridement group, 8.3; p = 0.47). The visual analog scale pain scores showed
      significance (control group, 19 mm; debridement group, 38 mm; p = 0.019), as did
      the POIS scores (control group, 18.3; debridement group, 6.1; p = 0.002). At 6
      months after surgery, again no difference was seen between the groups on either
      LKESs or SNOT scores. CONCLUSIONS: In our patient population, debridement after
      surgery did not affect disease-specific outcomes.

PMID- 24294688
TI  - Does bone mineral density have an effect on hearing loss in postmenopausal
      patients?
AB  - OBJECTIVES: An age-related decline in the bone mineral density (BMD) of the
      temporal bone, specifically in the segments that house the middle and inner ear,
      has been suggested as an additional risk factor for sensorineural hearing loss.
      We evaluated the effect of BMD on hearing loss in postmenopausal patients.
      METHODS: This study involved 120 postmenopausal women who were referred between
      May 1,2012, and September 1, 2012. The age range was 50 to 55 years (mean, 52.7
      +/- 2.3 years). The subjects were divided into three groups according to the
      results of BMD measurements. Of these, 30 were control subjects with normal BMD
      values, 45 had osteopenia, and 45 had osteoporosis. Each subject was tested with
      low- and high-frequency audiometry by a single experienced investigator under
      standard audiometric testing conditions. For each set of tests, mean values of
      air and bone conduction at each frequency and tympanometric values were
      calculated for the osteopenia, osteoporosis, and control groups. RESULTS: All
      three groups were designed to have similar mean ages and roughly equal durations
      of menopause and body mass indexes. At low frequencies (0.25, 0.5, 1, and 2 kHz),
      the differences in the mean air conduction threshold values among the three
      groups were not statistically significant (p > 0.05). At high frequencies (4, 6,
      and 8 kHz), the difference in the mean air conduction threshold values between
      the osteopenia and control groups was not statistically significant (p > 0.05),
      but that in the osteoporosis group was statistically significantly higher than
      those in the osteopenia and control groups (p < 0.05). At low frequencies (0.5,
      1, and 2 kHz), the differences in the mean bone conduction threshold values among
      the three groups were not statistically significant (p > 0.05). At 4 kHz, the
      difference in the mean bone conduction threshold values between the osteopenia
      and control groups was not statistically significant (p > 0.05), but that in the
      osteoporosis group was statistically significantly higher than those in the
      osteopenia and control groups (p < 0.05). There was no statistically significant
      difference among the three groups in tympanometric values (p > 0.05).
      CONCLUSIONS: We conclude that patients with low BMD values should routinely be
      counseled for an audiological assessment to detect any change in hearing
      thresholds.

PMID- 24294690
TI  - Competency assessment in the transfusion service: tips and tools.

PMID- 24294689
TI  - Differences in laryngeal neurotrophic factor gene expression after recurrent
      laryngeal nerve and vagus nerve injuries.
AB  - OBJECTIVES: Recurrent laryngeal nerve (RLN) and vagus nerve (VN) injuries
      characteristically are followed by differing degrees of spontaneous
      reinnervation, yet laryngeal muscle neurotrophic factor (NF) expression profiles
      after RLN and VN injuries have not been well elucidated. This study's objective
      was to determine the relative changes in gene expression of 5 well-characterized
      NFs from laryngeal muscle after RLN or VN injuries in a time-dependent fashion,
      and demonstrate how these changes correspond with electromyography-assessed
      innervation status. METHODS: Thirty-six male rats underwent left RLN transection
      (12 rats), left VN transection (12 rats), or a sham procedure (12 rats). The
      primary outcomes included electromyographic assessment and laryngeal muscle NF
      expression quantification with reverse transcription polymerase chain reaction at
      3 days and at 1 month. RESULTS: Electromyography at 3 days demonstrated
      electrical silence in the VN injury group, normal activity in the sham group, and
      nascent units with decreased recruitment in the RLN injury group. Reverse
      transcription polymerase chain reaction demonstrated that changes in NF gene
      expression from laryngeal muscles varied depending on the type of nerve injury
      (RLN or VN) and the specific laryngeal muscle (posterior cricoarytenoid or
      adductor) assessed. CONCLUSIONS: Laryngeal muscle NF expression profiles after
      cranial nerve X injury depend both upon the level of nerve injury and upon the
      muscles involved.

PMID- 24294691
TI  - Optimizing preoperative blood product orders at the Johns Hopkins Hospital.

PMID- 24294692
TI  - The clinical application of islet autoantibody testing for the diagnosis of
      autoimmune diabetes.

PMID- 24294693
TI  - Improving cytology lab safety and efficiency with direct-to-slide printers.

PMID- 24294694
TI  - Cytology information systems.

PMID- 24294696
TI  - High throughput sequencing: next generation methods.

PMID- 24294695
TI  - Vitamin D testing: what is right for your laboratory?

PMID- 24294697
TI  - Relevance of persistent infection with high-risk HPV genotypes in cervical cancer
      progression.

PMID- 24294698
TI  - Lead testing: the changes and challenges.

PMID- 24294699
TI  - Automated mass spectrometry. Will it revolutionize the microbiology lab?

PMID- 24294700
TI  - A battle with many fronts: clinical laboratories respond to economic challenges.

PMID- 24294703
TI  - Medically assisted aid in dying? Vermont is now the fourth state to permit mercy.

PMID- 24294702
TI  - Medical issues 2013-2014.

PMID- 24294704
TI  - Cancer incidence in elderly West Virginians.
AB  - West Virginia has one of the oldest populations in the nation. Cancer is a common
      disease among the elderly. With the projected growth of the elderly population
      (defined as 65 years and older), cancer will become a major public health burden.
      This article provides a summary of cancer incidence in elderly West Virginians.
      Incidence data were obtained from the West Virginia Cancer Registry.
      Approximately 6,262 elderly persons are diagnosed with some form of reportable
      cancer in West Virginia each year. Among those aged 65 and older, the four
      leading primary cancer sites in the order of their relative frequency were lung
      and bronchus cancer (21.8%), prostate cancer (14.6%), colorectal cancer (12.7%),
      and female breast cancer (9.6%). In general, the burden of cancer was greater in
      elderly men than in elderly women. Knowledge of the epidemiology of cancer in the
      elderly can potentially help guide statewide cancer prevention and control
      efforts and be used for anticipating future health care needs in the state.

PMID- 24294706
TI  - Audit of the current drug shortage.

PMID- 24294705
TI  - A rare cause of postpartum chest pain.
AB  - We report the case of a 45-year-old postpartum female at low risk for coronary
      artery disease (CAD) who presented with chest pain, a normal electrocardiogram
      (ECG) and elevation of serial troponin-T levels. Coronary angiography revealed
      dissection of the first obtuse marginal branch of the left circumflex coronary
      artery. The patient was treated medically and discharged home safely. Spontaneous
      coronary artery dissection (SCAD) is a rare condition. In the absence of CAD, it
      is seen most frequently in young females during the peripartum period. Insult
      from the hemodynamic stresses during pregnancy and labor combined with the
      underlying pregnancy related arterial wall changes is the proposed mechanism of
      dissection in this setting. The normal ECG in the presence of an acute myocardial
      infarction (AMI) in this case also demonstrates the occasional electrically
      silent ECG that can occur during acute compromise of the left circumflex coronary
      artery.

PMID- 24294708
TI  - An atypical presentation of testicular torsion: a case report.
AB  - Testicular torsion is an emergent condition requiring prompt surgical
      intervention to avoid permanent testicular compromise and death. As its symptoms
      overlap with other disease processes, diagnosis is sometimes difficult. When
      considering the presenting symptoms, one must be careful not to ignore unusual
      causes of torsion and misdiagnose the patient. In this case report we describe an
      unusual etiology of testicular torsion (traumatic) with an atypical patient
      presentation (mildly painful) which presented many obstacles before proper
      diagnosis and treatment.

PMID- 24294707
TI  - Acute arthritis of the hip--case series describing emergency physician performed
      ultrasound guided hip arthrocentesis.
AB  - We report two cases of acute hip arthritis where arthrocentesis was able to be
      performed rapidly, at the bedside by the emergency physician using ultrasound
      guidance, expediting diagnosis and patient care. In the first case, the patient,
      who was 23 weeks pregnant, was diagnosed with septic hip arthritis, taken for
      operative washout of the joint and did very well postoperatively with no
      pregnancy or other complications. In the second case, the patient was determined
      to have a noninfectious etiology and also did well. Skilled ultrasound guidance
      allows hip arthrocentesis to be performed by the treating clinician, decreasing
      the time to diagnosis and definitive care.

PMID- 24294710
TI  - Fractured OG tip: a case report.
AB  - This case report describes a complication from use of an orogastric tube not
      previously described in the literature. An OG tube was placed and removed non
      traumatically for the anesthetic management for an anterior-posterior cervical
      spinal fusion. Despite smooth placement and removal, the patient coughed up the
      tip of the OG tube while in the post anesthesia care unit. Orogastric (OG) and
      nasogastric (NG) tubes are routinely used in anesthesia as well as many other
      fields of medicine. OG and NG tubes leading to morbidity are rare; however, this
      report describes a new potential adverse event that clinicians should be aware
      of.

PMID- 24294709
TI  - Glove perforations with blunt versus sharp surgical needles in caesarean
      delivery: a randomized trial.
AB  - AIMS: To compare the rate of glove perforations and surgeon satisfaction when
      utilizing blunt surgical needles compared to conventional sharp surgical needles.
      METHODS: Patients undergoing Caesarean delivery were randomly assigned to the use
      of blunt or sharp surgical suture needles. Surgical team members reported any
      known needlesticks or perforations of gloves and the primary surgeon completed a
      survey to gauge their satisfaction with the needles. Glove perforation was
      assessed by suspending gloves and filling with water. The chi-square test was
      used to assess categorical variables and the Mann-Whitney U-test was used to
      assess ordinal data. RESULTS: A total 240 patients were enrolled into the study.
      There was no statistically significant difference in the rate of glove
      perforation per case between groups assigned to sharp (24%) or blunt surgical
      needles (26%). (RR 1.05, 95% CI 0.68-1.63). There were significant differences in
      the surgeon satisfaction surveys, with surgeons in the sharp needle group being
      more satisfied with the tissue penetration of the needle (p < .001), needle
      integrity (p = .01), force to penetrate tissue (p < .001) and control of bleeding
      at the needle insertion site (p = .001). Surveys from surgeons in the blunt
      needle group showed a statistically significant improvement in the perceived
      safety profile of the blunt needles (p < .001) CONCLUSIONS: There was no
      significant difference in the rate of glove perforation between blunt and sharp
      surgical needles during Caesarean delivery. Overall surgeons were more satisfied
      with the sharp surgical needles.

PMID- 24294712
TI  - Customized solutions for your special concerns--Part I.

PMID- 24294711
TI  - Sunshine Act update.

PMID- 24294713
TI  - West Virginia Reportable Disease Rule changes.

PMID- 24294714
TI  - Parkersburg physician is first MD to obtain CMCO Certification!

PMID- 24294715
TI  - [Society and health management].
AB  - The Health Management require acting according the social reality. The economic
      crisis for the unemployments and the State debts could affected to support Health
      System. The cost per capita: 1,800 euros. At Alma-Ata 1970 WHO improve Primary
      Care as open door in the Heath System. Some problems are common to all countries
      (frequency of diseases, demands, danger individual and community, feasibility of
      action, economic consequences, (PC in our country 15,7%). Should improve the
      Community development, and the environment. The participation of Primary Health
      Workers in the Management cover health care and community development and
      coaching, should be regularly supervised, and to avoid Risk Factor to Health.

PMID- 24294716
TI  - [Clinical aspects of the Langerhans cell histiocytosis in childhood].
AB  - The author reviews his clinical experience in this rare and fascinating disease,
      including nosologic, etiopathogenic, diagnostic and therapeutic aspects.

PMID- 24294717
TI  - [Electric channels, genetics and cardiac sudden death. Brugada syndrome as an
      example].
AB  - Since the introduction of molecular biology techniques hereditary diseases can be
      studied. These techniques allow us to locate the gene that causes a disease in a
      family. The identification of this gene not only permits to diagnose and
      potentially treat those affected by the abnormal gene, but also helps in a better
      understanding of the pathophysiology and molecular basis of non-familial forms of
      the disease. Although these techniques have been incorporated slowly in the field
      of cardiology, now the speciality is completely submerged in molecular biology.
      The first gene that was found was that of hypertrophic cardiomyopathy, in 1989.
      Since then, we have advanced in all heart family illnesses. Hypertension,
      arteriosclerosis, congenital diseases and arrhythmias have benefited from these
      techniques. The understanding of arrhythmias that cause familial sudden death due
      to long QT syndrome or Brugada syndrome has progressed a lot. The first
      genetically guided therapy studies have shown that in the near future patients
      will receive a therapy according to their genetical default. Looking how fast
      these techniques are evolving, and the impressive advances of the Human Genome
      Project, probably the remaining genes causing familial diseases will be described
      in the coming years. These results are very encouraging and indicate a clear need
      to make a genetic diagnosis in all patients with these diseases. The diagnostic
      and therapeutic implications of these findings can be of enormous importance for
      our patients.

PMID- 24294718
TI  - [Neurobiology of neuronal circuits invoved in depression].
AB  - Many authors consider the most important step in understanding depression is to
      identify the neural systems responsible for this disease, thereby allowing
      treatment to be guided towards specific targets. Some of the neural networks that
      are involved in depression are already known thanks to molecular, neuroimaging,
      pathological and functional studies. Specific increases or decreases in certain
      activities, certain lesions and biochemical alterations and receptors as well as
      plasticity processes that are involved in depression-associated neural networks
      have been identified. These networks include cortical and subcortical structures
      that modulate cognitive and emotional aspects of behavior and the neural systems
      related to decision making and energy-vitality in thought and action. This
      article reviews and presents the best-studied networks and the alterations that
      are most likely to be involved in the pathophysiology of depression that can be
      summarized in the following points: 1) The medial prefrontal network is a nodal
      link of the neural network involved in the major (MDD) and bipolar (BD)
      depressive disorders, here the anatomical connections in the macaque monkey of
      one of the most distinctive components of this network: the medial orbitofrontal
      cortex are reviewed based on the findings of our group. 2) The neuroimaging and
      pathological findings in terms of size, composition and functionality of brain
      structures, specially this network, in patients with MDD and BD are summarized.
      3) The neural circuit involved in the MDD and BD is proposed and discussed. 4)
      The results of the first well regulated and controlled study on deep brain
      stimulation for treatment-resistant MDD and BD patients are presented.

PMID- 24294719
TI  - [Groundwater].
AB  - From the perspective of Hydrogeology, the concept and an introductory general
      typology of groundwater are established. From the perspective of Geotechnical
      Engineering works, the physical and mathematical equations of the hydraulics of
      permeable materials, which are implemented, by electric analogical simulation, to
      two unique cases of global importance, are considered: the bailing during the
      construction of the dry dock of the "new shipyard of the Bahia de Cadiz" and the
      waterproofing of the "Hatillo dam" in the Dominican Republic. From a physical
      fundamental perspective, the theories which are the subset of "analogical
      physical theories of Fourier type transport" are related, among which the one
      constituted by the laws of Adolf Fick in physiology occupies a historic role of
      some relevance. And finally, as a philosophical abstraction of so much useful
      mathematical process, the one which is called "the Galilean principle of the
      mathematical design of the Nature" is dealt with.

PMID- 24294720
TI  - [Schizophenia and premorbid infections].
AB  - Schizophrenia is a disease of unknown etiology. Many authors have studied its
      association with infections. By meta-analysis viruses are the most studied
      agents, relationship with the Borna virus and human endogenous retrovirus W.
      Also, C. pneumoniae and C. psittaci DNA in blood are more common in patients.
      Finally, there is association with parasitism by T. gondii, despite the existence
      of publication bias. Serologically, in our environment, anti-Toxoplasma IgG may
      be a risk factor related to schizophrenia, and may have potential value for
      better diagnosis and prevention.

PMID- 24294721
TI  - [New strategies for secondary prevention of cervical cancer].
AB  - The current incidence of cervical cancer is around 5,300,000 new cases per year
      worldwide and mortality 275,000 cases per year. The 80% of these cases are
      distributed in developing countries. Cervical cancer screening should cover to as
      much population as possible, for instance, through public health initiative;
      should be use previously validated test, and based on primary care. The
      efficiency is the basic criterion of this screening. The Pap smear is the best
      technique ever used by the Preventive Medicine; and in countries with sufficient
      capacity and proper application, the incidence/mortality can be decreased until
      75%. The introduction of DNA-HPV testing has increased the sensitivity of
      detecting cervical cancer, but with lower specificity. Actually it has been
      incorporated into the cervical screening as proposed by the Spanish Society of
      Obstetrics and Gynecology. The cervical screening must be maintained even in
      women who have been vaccinated; because of they may be at risk of contact with
      other high-risk HPV types not included in the vaccine. In the future, biomarkers
      will be of great importance. Inactivation of the retinoblastoma suppressor gene
      by the oncogene HPV E7 increases levels of p16INK4a in cytoplasm. Overexpression
      of nuclear antigen Ki67 is a marker of cell proliferation by HPV infection.

PMID- 24294722
TI  - [Tissue engineering of peripheral nerve].
AB  - The use in traumatic peripheral nerve pathology of conduits of different
      materials to connect the severed nerve ends and facilitate nerve fibers
      connection has not so far led to very satisfactory results. This paper presents
      preliminary results on the use of tissue engineering techniques to facilitate
      nerve regeneration using those conduits. Research carried out by clinical,
      histological, histochemical and neurophysiological methods shows a higher degree
      of nerve regeneration regarding the controls when a fibrin-agarose biomaterial is
      introduced in the conduit and even more when stem cells from the fat of the
      experimental animal are added to the fibrin-agarose biomaterial. These results
      could contribute to develop in the future better effective therapeutic results in
      traumatic peripheral nerve pathology.

PMID- 24294723
TI  - [Anankastic phenomena in psychiatry (predestination and dace in mental life)].
AB  - The purpose of this communication is to compare behavioral mineralization
      occurring in mental illness to the freshness and plasticity behavior in health.
      The epistemological fundamentals of this paper include the theories of chaos and
      complexity of Edgar Morin, the concept of autopoiesis developed from the theory
      of systems, the latest discoveries on the neurobiology of consciousness and their
      associations with Darwinian psychiatry and also, following Lain Entralgo,
      recreating the Greek concept of ananke to describe the behavior fixation in an
      anachronistic place of the physis in mental illness. It provides some empirical
      evidence to support the proposal, and all this is rigorously examined with
      hermeneutic phenomenology and its theoretical possibilities. This leads to an
      epistemological rethinking of clinical and therapeutic proposal aimed at the
      subject and the recovery of his or her freedom.

PMID- 24294724
TI  - [The Guadalupe's Monastery and the teaching of medicine].
AB  - The Monastery of Guadalupe was an important medical science teaching center from
      late Middle Ages until 1835, as a result of the high qualification of its
      professionals, its excellent facilities and perfect organization. Subsequently,
      we analyze the origin of the monastery and its government, the hospitals it held,
      its organization and functioning, and medical practice. We conclude with selected
      thoughts about the consideration of the Monastery as a School of Medicine, and a
      mention of some outstanding caregivers.

PMID- 24294725
TI  - [Academician D. Pedro Mata on the second centenary of his birth].
AB  - On 14 June 2012 marked the second centenary of the birth of Peter Mata, one of
      the most unique personalities medical Spanish doctor of the panorama of the
      nineteenth century. On the occasion of this anniversary is concisely recalls his
      biography, especially as the creator of the Forensic Medicine in Spain, and
      recalls its activity as Academician of the Royal National Academy of Medicine, an
      institution that was the protagonist after reading a speech in which he called
      overcome the work of Hippocrates.

PMID- 24294726
TI  - [Aging and inflammation: Klotho, diet and the kidney connection].
AB  - Despite renal replacement therapy mortality among chronic kidney disease patients
      is 10-1000-fold higher than in age-matched controls. Klotho is a kidney protein
      with anti-ageing hormonal properties that is also a co-receptor for the FGF23
      fosfatonin. There is a bidirectional relationship between Klotho and
      inflammation. Thus, inflammation decreases renal Klotho and Klotho has anti
      inflammatory properties. Mice with genetic defects in Klotho suffer from
      accelerated aging and early death. Decreasing the phosphate load improves the
      phenotype and prolongs survival in these mice. Unraveling the Klotho-phosphate
      inflammation interaction may open new avenues for research that may improve the
      outcomes of kidney patients as well as provide new tools to retard aging in the
      general population.

PMID- 24294727
TI  - [Robert Koch, eminent medical bacteriologist, creator of the applied microbiology
      and its technnology].
AB  - In our communication we wish consider to bring at a first instance the egregious
      figure of Robert Koch a hundred of years after his dead. Nobody else had
      contributed so much in the development of the bacteriology as unic and
      independent science. Several books and biographical sketchs had been published
      about Koch in german, english and french, mainly, with differents detais and
      interpretations, about his life. However, nobody doubred about his innovator
      spirit and scientist at highest level. This communication revise and discuss
      diverse chapters about his life as innovator, researcher, groups leader and
      Magister.

PMID- 24294728
TI  - [A new prevention strategy against meningococcal disease: the menigococcus B
      vaccine].
AB  - The new anti-meningococcal vaccine contributes not only to fight against a severe
      condition like the meningococcal disease caused by meningococcus B, but also
      gives us a new tool: inverse vaccinology. This technique parts from the bases of
      the virtual knowledge of the microorganism's genome, knowing all the proteins
      that the pathogen is able to express on its surface. This allows us to predict
      the candidate antigens which are most likely to be used in a potential vaccine.
      After the selection of these candidates, the vaccines are studied first in
      animals and later in humans. All this research was successful for the anti
      meningococcal vaccine candidate and has allowed to obtain, through inverse
      vaccinology, a 4CMenB vaccine, containing 4 protein components, obtained from the
      meningococcus B genome, with antigenic potential to induce immune response. This
      guaranties an appropriate protection without the possibility of reversion of the
      microorganism to cause the disease. This new finding and this new vaccine could
      significantly change the future of meningococcal disease worldwide.

PMID- 24294729
TI  - [Near death experiences].
AB  - Near Death Experiences are those accounted by people who after being clinically
      dead return to life spontaneously or after reanimation. These experiences have
      been used traditionally to support the belief in the existence of the soul and of
      life after death. However, today neuroscience tries to explain these experiences
      from the scientific point of view, i.e. explaining them based on their brain
      substrates. Their resemblance to mystic experiences and to altered states of
      consciousness seems to indicate that they may be produced by hyperactivity of
      limbic structures caused by anoxia or hypercapnia.

PMID- 24294730
TI  - [Treatment and prevention of tobacco addiction. Antinicotinic vaccine].
AB  - Tobacco addiction and its consequences are considered the leading avoidable cause
      of death, because of the great addictive power of nicotine, the main component in
      tobacco preparations. The addictive mechanism of nicotine is the stimulus of
      nicotinic cholinergic receptors at the mesolimbic areas of the brain, which in
      turn stimulate dopamine release in the brain centres of reward (mainly n.
      accumbens). Treatment of tobacco addiction includes nicotine replacement therapy
      (gums and dermal patches), pharmacological therapies (i.e. bupropion,
      varenicline) as well as behavioural and psychological support. Vaccination
      against nicotine addiction is a new approach, still in study (ongoing phase III
      clinical trial) as new treatment of tobacco addiction. The efficacy of such
      vaccines for smoking cessation is dependent upon their ability to increase
      concentration of nicotine antibodies. Nicotine vaccine stimulates immune system
      leading to the production of nicotine specific antibodies. These are linked to a
      larger carrier protein resulting complex too large to cross the blood-brain
      barrier, leading to a blockade of dopamine releasing mechanisms in the brain
      rewarding circuit. Several clinical trials currently carried out to assess the
      ability of nicotine vaccines in the prevention of tobacco dependence are reviewed
      here.

PMID- 24294731
TI  - [Present role of CT/PET in diffuse large B-cell lymphoma].
AB  - The Diffuse Large B-Cell Lymphoma is the most frequent non Hodgkin Lymphoma. The
      role of CT/PET in this relatively homogeneous group of lymphomas is
      controversial. It rarely changes the management of the patients in the initial
      staging. Recents publications, clinical trials and experts consensus meetings
      have demonstrated its utility in the evaluation of the response at the end of the
      treatment. The interest of CT/PET in the evaluation of the response during the
      treatment, with the objective of implement a "Risk Adapted Therapy", in
      increasing.

PMID- 24294732
TI  - [Vitamin D. A geriatric updated perspective].
AB  - The aim of this review is to offer an updated survey about the relationship
      between old age, vitamin D and different clinical conditions. Two third of people
      over 65 years has insufficient serum levels of vitamin D (<30 ng/ml). Almost half
      of them present deficiency (<20 ng/ml), severe in many cases (<15 ng/ml). This
      proportion increases when we analyze non-white populations, women, and people
      with obesity, diabetes mellitus or diets poor in Vitamin D. Low serum vitamin D
      concentration has been linked to mortality, osteoporosis, falls propensity,
      fractures, frailty, and cardiovascular diseases, including hypertension. Several
      epidemiological studies open the possibility to a relationship between low levels
      of the vitamin D and many other diseases. Among them with different cancer,
      diabetes, some types of dementia, Parkinson's disease, macular degeneration or
      periodontitis. Also with muscle strength, mobility and physical performance.
      Vitamin D supplementation has beneficial clinical effects, with a significant
      reduction of risks, specially in subjects living in nursing-homes and in those
      treated with corticoids or antireabsortive drugs. These effects are doses
      dependent. Risk of intoxication is minimal, even with high doses of vitamin.

PMID- 24294733
TI  - [Academies Institute Andalucia].
AB  - Academies Institute of Andalusia is the only corporation in the State grouping
      twenty seven Spanish Academies and Royal Academies of an autonomous region, with
      a total of 760 Academicians. This paper sets out as conceived, their roles and
      relationships with other national corporations, as well as the primary mission to
      maintain and strengthen fraternal relations, culture, research and collaboration
      between the Andalusian Academy, showing academic representation whole of them.

PMID- 24294734
TI  - [Sequencing and their use in the study of fundamental HIV virus].
AB  - The only massive sequencing genomes, also known as Ultra Deep Sequencing (UDS),
      has allowed great advances in the field of biomedical sciences. In the field of
      virology, is an excellent opportunity to study the genetic variability of the
      virus. Therefore, in the scenario of a virus with high replication capacity and
      high error rate of the enzyme that is responsible for this process, such as the
      Human Immunodeficiency Virus (HIV), the UDS provides a tool particularly useful
      to characterize more fully the details related to its variability. In this
      regard, one of the greatest advances has been the characterization of what has
      been termed "virus founders" in HIV infection, the disclosure is of particular
      importance in the development of vaccines against HIV. This technology also
      allows the estimation of HIV related virological aspects as important as
      population dynamics, viral evolution, and the study and characterization of
      superinfections and superinfections.

PMID- 24294735
TI  - [Personalized medicine in oncology: one drug, one biomarker].
AB  - Sir Williams Osler, the father of Modern Medicine, recognized more than one
      century ago, that "If it were not for the great variability among individuals,
      medicine might as well be a science and not an art". Nevertheless today, in our
      opinion this paradigm is presently in crisis. Clinical medicine starts to be a
      science thanks to this variability that is generating a personalized medicine
      based on the concepts of pharmacogenetic and pharmacogenomic. In the Medical
      Oncology field this era has begun: today the determination of mutations in
      several given genes such as Her2, KRAS, EGFR, ALK, and BRAF is translating into a
      individualized strategy that produces benefits that are clearly superior to
      present indiscriminate therapeutic decisions. This strategy is more active, more
      safe and also more efficient.

PMID- 24294736
TI  - [Preceptor's address. In memory of Manuel Armijo Valenzuela].

PMID- 24294737
TI  - [Prognostic factors and prognostic groups for overall survival of cervical cancer
      patients FIGO stage IB1].
AB  - A petro-prospective study on 132 women with early invasive cervical cancer was
      performed. According to Log-Rank test, Breslow and Tarone-Ware tests we analyzed
      the following factors: age, type of histology, tumor grading, tumor localization
      (exo-, endocervix), lymph node metastases, postoperative histologic findings,
      blood transfusion and Hb on the day of discharge. We found as an independent
      prognostic factors for overall survival: tumor localization, postoperative
      histologic findings and blood transfusion. Based on these factors two profnostic
      groups were created with favorable and unfavorable prognosis. The median survival
      for these two groups was 106 and 57 months, respectively.

PMID- 24294738
TI  - [Our experience in using liquid based cytology in cervical screening (LBC)].
AB  - AIM: Our aim is to summarize our experience in screening for cervical cancer
      using liquid-based cytology system and the Bethesda system. MATERIAL AND METHODS:
      We did a clinical study of 92 patients, aimed to summarize the results of liquid
      based cytology based on various criteria such as specificity, sensitivity,
      positive and false negative results. All patients had conventional Pap smear as
      well. RESULTS: The better results stand out of the LBC, mainly due to the reduced
      number of unsatisfactory results and higher specificity and sensitivity for low
      grade lesions--LSIL. There is better standardization of samples, because of the
      automation of the process. The method is much better quality and more economical.
      CONCLUSION: The results obtained by us confirm the diagnostic quality and
      efficiency of the method, so we offer routine use in Bulgaria, as it is in some
      developed countries.

PMID- 24294739
TI  - [Preoperative sonovue contrast color Doppler in patients with cervical cancer.
      Preliminary report].
AB  - OBJECTIVE: Angiogenesis has gained much attention in oncology in recent years.
      The purpose of this pilot study was to describe the preoperative sonographic
      patterns of SonoVue Contrast-Doppler ultrasound and the standard Color Dopper
      ultrasound of cervical cancer tumor angiogenesis. MATERIALS AND METHODS: This is
      a prospective observational study. The study included fifteen patients with
      proven cervical cancer. RESULTS: Contrast Doppler US after the SonoVue injection
      gave a good picture of the intense intralesional tumor angiogenesis. Of the 15
      patients with FIGO stage lb1 Contrast-sonography showed 12 patients stage Ib1, 1
      stage Ib2, 1-stage IIb and 1-stage Iva at final diagnosis. CONCLUSIONS: SonoVue
      Contrast Doppler Ultrasound gave a better definition of the margins of the
      neoplastic lesions in the cervical cancer Because contrast agents increase the
      sensitivity of detection of parametrial invasion and lymph node metastases, they
      could pay an important role in the evaluation of uterine cervical cancer

PMID- 24294740
TI  - [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and
      healthy women of reproductive age].
AB  - Polycystic Ovary Syndrome is the most common endocrine disorder in women of
      reproductive age, whose final pathogenesis remains unclear. PCOS is a distinctive
      disorder of follicular growth leading to obstruction of the selection of the
      dominant follicle, and as a result--arrest at small antral follicles. Anti
      Mullerian hormone (AMH) is a glycoprotein produced in the granulosa cells of the
      ovary and having regard to the regulation of growth and development of follicles.
      Study of the relationship between AMH and PCOS are conflicting and few. It is
      believed that women with PCOS had significantly higher levels of AMH compared
      with healthy, which is associated with an increased number of antral follicles
      pre-or is the result of a specific offense of AMH synthesis by the granulosa
      cells causes follicular arrest in PCOS. OBJECTIVES: Comparison of serum anti
      Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS) and
      healthy women (control group). As too study of correlation between serum Anti
      Mullerian hormone (AMH) and other hormonal parameters. DESIGN: Prospective
      comparative study. MATERIAL AND METHODS: This study was conducted in the
      Department of Obstetrics and Gynecology at the Medical University of Plovdiv and
      the Department of Endocrinology at the Medical University of PIovdiv. We studied
      the 100 women aged between 18-35. Divided into two groups: 50 women with
      polycystic ovary syndrome (PCOS) selected according to the criteria of the
      American Society of Reproductive Medicine (ASRM)--Rotterdam in 2003 and control
      group of 50 healthy women. 15 women with PCOS and amenorrhea. Serum levels of
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone,
      androstenedione, estradiol (E2) and Anti-Mullerian hormone (AMH) were measured
      during the early follicular phase (3-5 days) of spontaneous menstrual cycle or
      progestin-induced uterine bleeding. RESULTS: There was a statistically
      significant difference in serum AMH when compared to the values in the two groups
      subject to the study. In group of women with PCOS are found positive correlation
      between serum levels of AMH and androstenedione, testosterone and luteinizing
      hormone and negative correlation between AMH, FSH and E2. CONCLUSION: In this
      study group of women with PCOS had significantly higher serum levels of AMH
      compared with the control group. The presence of positive and negative
      correlations with other hormonal parameters revealed parts of AMH involvement in
      the pathogenesis of PCOS. These data on serum AMH levels in PCOS allow its use as
      a diagnostic criterion, but also the study of the level can serve as a reliable
      tool to characterize the severity of the syndrome, monitoring and forecasting.

PMID- 24294741
TI  - [Our and foreign experience in modern surgical treatment of cervical
      adenocarcinoma stage T(1A1)].
AB  - AIM: The aim of this research work was to evaluate the distant results in
      patients with cervical adenocarcinoma stage T(1A1) treated conservatively only by
      conization. MATERIAL AND METHODS: 60 patients were) examined for 10 years period
      with cervical adenocarcinoma stage T(1A1) (stromal invasion to 3 mm in deapth and
      7 mm horizontal spread). RESULTS: 50 patients were surgicaly treated by cold
      knife conization and 10 patients by LLETZ. In 40 patients a total hysterectomy
      was additionally performed. 20 patients (age range from 20 to 40 years) were
      treated only by conization because they desired to preserve fertility. In 12
      patients an attempt was made for to get pregnant. In 7 patients there was a
      successful pregnancy. CONCLUSIONS: The conization of the uterine cervix as the
      only treatment in patients with cervical cancer T(1A1) adenocarcinoma is
      effective and safe therapy. It is very important when patients desire to save
      their reproductive functions. The individualization of this treatment method is
      not yet obligatory because of the small number of treated patients.

PMID- 24294742
TI  - [The effect of vaginal sildenafil citrate on uterine blood flow and endometrium
      in the infertile women].
AB  - Evaluation of endometrial receptivity remains a challenge in clinical practice.
      Ultrasound evaluation of endometrial thickness and texture and measurement of
      uterine artery blood flow has been used for endometrial assessment. AIM: To
      investigate the role of combination of sildenafil citrate and serophene on
      endometrial thickness, endometrial volume, endometrial FI and VFI on
      Angiohistogram, RI and PI to a. uterine on the day of hCG, in prediction of IUI
      outcome in infertile women. MATERIALS AND METHODS: Forty two patients were
      selected randomly who had anovulatory infertility. In Sildenafil citrate plus
      Serophene group (Group I), patients got 25 mg sildenafil citrate (Silden)
      vaginally and Serophene 100-150 mg orally, and in Serophene group (Group II), 100
      150 mg of Serophene was given orally. RESULTS: Mean endometrial thickness and
      endometrial volume was 11.8 +/- 2.6 v/s 10.2 +/- 2.8 and 5.2 +/- 1.4 v/s 3.6 +/-
      1.8 respectively in group I and in group II (p < 0.05). There was significant
      decrease in PI and RI to a. uterina in group I. CONCLUSIONS: Combination of
      Sildenafil citrate and Serophene is an effective agent as a first-line of
      treatment for ovulation induction.

PMID- 24294743
TI  - [Oncologucal results after surgical and radio-surgical treatment in patients with
      cervical cancer stage Ib1].
AB  - One hundred thirty two patients with cervical cancer stage IB1 were evaluated for
      desease free (DFS) and overall survival (OS). All women were submitted to surgery
      radical hysterectomy class III and pelvic and/or paraaortic lymph node
      dissection. Ninety three women were irradiated after surgery-telegamma therapy
      (TGT) 50-52 Gy. After median period of follow-up 44 months (from 1 to 114) OS and
      DFS were estimated using Kaplan-Meier method. Five-year OS and DFS were 83% and
      82%, respectively.

PMID- 24294744
TI  - [Probiotic monotherapy of bacterial vaginosis: a open, randomized trial].
AB  - The aim of the current research is to establish the clinical and microbiological
      efficacy of the therapy with local probiotics in the treatment of anaerobic
      vaginal infections and the therapy's effect upon vaginal flora. STUDY
      DESIGN/METHODS: 381 (100%) women with bacterial vaginitis are included in the
      research. They were randomized into three groups. In the first group 143 women
      who were treated with local (10 applications) probiotics vaginal medicine,
      containing live lactobacillus types Lactobacillus acidophilus, Lactobacillus
      rhamnosus. In the second group 126 patients were treated with five days oral
      administration of Clindamycin (tabl.x 600 mg) BID and local therapy of two
      vaginal ovules containing each 1000 mg Metronidazole, which were administered
      intravaginal every other day. In the third group 112 women were treated with the
      same therapy as the second group and in addition started from the day 5 after it
      were administered locally probiotic medicine containing Lactobacillus acidophilus
      u Lactobacillus rhamnosus. The efficacy of the therapeutic scheme was evaluated
      via comparison of patients' clinical complains in the different groups, of data
      from clinical examinations (Amsel) and microbiological tests (Nugent) for each
      patient. RESULTS: Thirty five-forty days after the probiotic therapy, the
      clinical efficacy in this group (Amsel) is 42.7% and microbiological efficacy
      (Gram preparation - Nugent)--41.3%. They are lower than the results which we
      received in the groups where the combine nitroimidazole/incozamide treatment was
      performed with or without local probiotic. The second group: clinical efficacy-
      51.6%, microbiological (Nugent)--46.4%. The highest clinical--87.5% and
      microbiological--80.3% efficacy showed the combine
      nitroimidazole/lincozamide/probiotic treatment in the third group. CONCLUSIONS:
      Our results show that the local monotherapy with probiotics has fewer efficacies
      in comparison to the combine therapeutic schemes for treatment of vaginal
      disbacteriosis with dominant anaerobic species.

PMID- 24294745
TI  - [Postmenopausal osteoporosis. Role of vitamin K in the prevention of
      osteoporosis].
AB  - Low vitamin K1 intake and low plasma vitamin K1 levels are associated with low
      bone mineral density (BMD) and increased osteoporotic fracture risk in
      postmenopausal women. Despite the lack of a significant change or the occurrence
      of only a modest increase in bone mineral density, high-dose vitamin K(1)
      supplementation improved indices of bone strength in the femoral neck and reduced
      the incidence of clinical fractures.

PMID- 24294746
TI  - [Effect of Lactobacillus casei var rhamnosus (Gynophilus) in restoring the
      vaginal flora by female patients with bacterial vaginosis--randomized, open
      clinical trial].
AB  - The vaginal probiotics can increase the clinical and microbiological efficacy of
      the therapeutic regimens used for the treatment of bacterial vaginosis. The Aim
      of our study was to evaluate the effect of the application of Lactobacillus casei
      var rhamnosus (Gynophilus--probiotic species Lcr 35) in restoring the vaginal
      flora and prevention of relapses by female patients with anaerobic vaginal
      infection undergoing conventional (nitroimidazole) local and main therapy.
      METHODS: In the study were included 60 women with established Amsel/Nugent
      bacterial vaginosis who were randomized in two groups. The first group patients
      (n-30 beginning/n-25 controls) underwent a 5 day treatment with two daily peroral
      doses of metronidazole 500 mg, with local application of metronidazole ovules
      1000 mg at the 1st and the 3rd day (M+M). In the second group (n-30 beginning/n
      26 controls) the therapeutic regimen was the same as in the first group, with
      additional 7 day treatment with Lactobacillus casei var rhamnosus - Lcr 35.
      (Gynophilus) vaginal ovules, two daily doses (M+M+G). RESULTS: 30% to 40% was the
      difference/enhance of the clinical efficacy according to the clinical indicators
      when Lactobacillus casei var rhamnosus - Lcr 35 was added to the standard
      nitroimidazole therapy. Concerning the main clinical indicator: Amsel criteria,
      the improvement after the therapy in the first group (M+M) was 60% (n-15) and in
      the second group (M+M+G) 88.5% (n-23). According to the microbiological
      indicators the improvement in the first group (M+M) based on the vaginal flora
      evaluation (Nugent score) was 60% (n-15) and in the second group, after the
      addition of Lcr 35 it was 88.5% (n-23). CONCLUSIONS: The application of
      Gynophilus after conventional 5-nitroimidazole treatment for bacterial vaginosis
      increased the clinical and microbiological efficacy of the therapy by 25% - 30%.
      The microbial balance in the vaginal ecosystem was restored in the majority of
      patients (88%), which is a prerequisite for low percentage of bacterial vaginosis
      relapses.

PMID- 24294747
TI  - [Truscreen - Preliminary results].

PMID- 24294748
TI  - [Multiple primary neoplasms in the gynecological practice - characteristics,
      rareness and follow up algorithm ].

PMID- 24294749
TI  - [PlGF and sFlt-1--diagnostic significance in preeclampsia prediction in pregnant
      women with gestational and chronic hypertension].
AB  - Preeclampsia (PE) is characterized with hypertension and proteinuria after 20
      gestational weeks. and is the major reason for maternal and fetal mortality
      during pregnancy. Etiology of PE is still unclear. Clinical manifestation is
      connected to high levels of circulated anti-angiogenic proteins such as soluble
      Fms-like tyrosine kinase 1 (sFlt1) and soluble endolgin (sEng). Furthermore PE
      leads to low serum levels of Placental growth factor (PIGF). The change of these
      serum levels appears before clinical manifestation, which makes them useful for
      screening of pregnant women with high risk of PE. This opportunity for prediction
      of PE would significantly lower the mortality caused by PE. We measure serum sFlt
      1 and PIGF levels in pregnant women with normal and pathological pregnancy
      including gestational and chronic hypertension without PE. Population included 23
      pregnant women during a period of two years. Comparison between the groups was
      made with parametric Student's test. A level of p < 0.05 was accepted as
      statistically significant. Eight women were with PE (one of them with chronic
      hypertension). Six pregnant women were with isolated hypertension (four with
      chronic and 2 with gestational hypertension). Nine pregnant women were with
      normal pregnancy. Serum sFlt-1 and PIGF levels showed significant differences in
      pregnant women in between 25th and 28th gestational weeks: a) for sFlt-1--in PE
      (4859.88 pg/ml) and normal pregnancy (3125.53 pg/ml)--p = 0.0002 or isolated
      hypertension (2791.40 pg/ml)--p = 0.0054 and b) for PIGF--in PE (206.63 pg/ml)
      and normal pregnancy (667.87 pg/ml)--p = 0.0011 or isolated hypertension (560.20
      pg/ml)--p =0.0125. Our study shows that serum sFlt-1 and PIGF levels
      significantly changes during pregnancy and before clinical manifestation of PE
      (minimum in 15.5 gestational weeks).

PMID- 24294750
TI  - [Nonspecific immunomodulation in obstetrics and gynecology with Ecomer
      preliminary report].
AB  - The article gives a brief description of "Ecomer", preparation containing shark
      liver oil. Main immunoactive ingredient of the shark liver oil are the
      alkylglycerols. The main characteristics of alkylglycerols are noted together
      with their mechanism of action. There is also a list of indications for Ecomer
      administration. There is a summary of the authors' experience with Ecomer, its
      efficacy in ObGyn being the main aim of this study. METHODS AND MATERIALS: For
      the purpose of the study Ecomer is given to two main groups of patients: I
      pregnant women between 27 and 36 weeks of gestation having two subgroups: 1--with
      8 women with naso-pharyngeal complaints and 2--with 13 patients with urinary
      tract complaints, suggestive of cysto-pyelitic disorders and II main group of
      patients operated for cervical cancer in different stages with two subgroups--1
      with 17 patients with Ecomer intake started at the beginning of the radiation
      therapy, and 2 with 6 patients who began taking Ecomer before the beginning of
      the radiation therapy, after having a histologically proved diagnose. The I group
      took two capsules of Ecomer three times a day for 15 days or less if asymptomatic
      earlier; in the II group Ecomer was taken two capsules three times a day for 2
      months, then one capsule three times a day for a month, followed by a repetition
      of the scheme. RESULTS: In the pregnant women group, improvement was noticed in
      75% in the first subgroup and in 76% in the second subgroup. In the second main
      group the interpretation of results is hindered by the insufficient time
      interval. Nevertheless, fewer side effects of the radiation therapy was noticed
      in both groups. Improvement in the survival rate is yet to be followed up.
      CONCLUSIONS: Administration of Ecomer in pregnant women with naso-pharyngeal
      problems led to improvement in their general condition and less frequent need to
      prescribe antibiotics. In pregnant women with urinary tract problems, Ecomer
      resulted in easing the pain faster and lowered the recurrence risk. In women with
      cervical cancer, the treatment is quite aggressive and the opportunity to
      diminish the side effects by administration of a natural and harmless preparation
      should not be omitted.

PMID- 24294751
TI  - [A case with Azoospermia and YQ- chromosome microdeletion, affecting its proximal
      region Azoospermia factor-A (AZFA) ].

PMID- 24294752
TI  - [Hyalobarrier Gel and Hyalobarrier Gel Endo. Sterilization using hydrogen
      peroxide vapor ].

PMID- 24294753
TI  - [Challenges in front of the modern obstetrics and gynecology].

PMID- 24294754
TI  - [Contemporary methods for preterm labor diagnostics].
AB  - Authors track current trends in preterm labor diagnostics. The emphasis is laid
      on biochemical tests for examination of fibronectin (fFN) and insulin-like growth
      factor-binding protein (IGFBP-1) in cervical and vaginal secretions, as well as
      ultrasound assessment of cervical length.

PMID- 24294755
TI  - [Preterm birth--incidence and etiology].
AB  - Preterm birth is a major societal and economic problem. To him is accounting for
      80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a
      complex multifactorial condition with different underlying etiologies. Paramount
      in the prevention of preterm birth is physician education regarding known risk
      factors, signs and symptoms of preterm labor and the role of close follow-up in
      the patients identified as high risk.

PMID- 24294756
TI  - [Intraamniotic infection--cause and satellite of preterm birth].
AB  - Intraamniotic infection (IAI), most commonly presented as chorioamniotitis, plays
      a major role in the pathogenesis of preterm birth (PTB). In this study, we sought
      for signs of IAI through clinical and laboratory parameters (leukocyte count, CRP
      concentration and IL-6 in maternal blood), and compared those to the newborns'
      infectious condition. Using cervical and vaginal secretion cultures, we
      determined the probable causing agents of IAI. We also followed up the
      therapeutic effect from the use of corticosteroids, tocolitics and antibiotics
      for the treatment of PTB. The results demonstrated that over 46% of the pregnant
      women with PTB presented with evidence of IAI. The best diagnostic option to
      detect an IAI provides maternal blood IL-6, and the combination between leukocyte
      count and CRP is a must for routine examinations. We did not isolate a single
      vaginal pathogen but a combination of harmful microbes which provided evidence of
      a vaginal ecosystem disorder. The combination therapy in over 50% of women had a
      positive effect on PTB for the period of corticosteroid prophylaxis (72 hrs).
      From hour 84, antibiotic therapy can no longer control IAI development.

PMID- 24294757
TI  - [HIV infection in pregnant women and risk of preterm birth].
AB  - According to estimates by WHO and UNAIDS, 34 million people were living with HIV
      at the end of 2011. Transmission of the human immunodeficiency virus (HIV) from
      mother to child can occur in utero, during labour or after delivery from
      breastfeeding. The majority of infants are infected during delivery. Clinical
      records have found more evidence of an increased rate of preterm delivery in HIV
      positive women in low income countries.

PMID- 24294758
TI  - [Pregnancy termination in Bulgaria - past, present and future perspectives. Drugs
      induced abortion - guidelines by WHO].
AB  - There are still too many unsafe abortions performed worldwide. Together with the
      efforts to reduce the abortion by choice, we note a rise in the need for mid
      trimester pregnancy termination for medical reasons. The article looks at the
      past present and future perspective of the abortion as a procedure in Bulgaria.
      States the fact that medical abortion is officially not widely performed. We
      reckon that with the existing guidelines by WHO and with Mifepriston and
      Misoprostol recently registered in Bulgaria, it is time for the medical abortion
      to become part of the clinical practice in Bulgaria. We believe that early
      medical abortion as well as mid trimester induced abortion is and adequate if not
      better alternative to the existing in Bulgaria procedures.

PMID- 24294759
TI  - [Again about the drug induced abortion].
AB  - Medical abortion is known as a non-aspiration or non-surgical abortion for
      terminating an unwanted pregnancy up to 63 days' gestation. It is not officially
      regulated in Bulgaria.

PMID- 24294760
TI  - [Mid trimester pregnancy termination--review of the caseload for 2012 of
      Maternity University Hospital 'Maichin Dom', Sofia, Bulgaria].
AB  - Midtrimester pregnancy termination is yet an ongoing clinical issue in spite of
      the hard work on the matter in the recent years. There is a significant
      withdrawal from the surgical methods, absence of adequate drug preparations for
      medical termination and absence of guidelines for such form the Bulgarian Society
      of Obstetricians and Gynaecologists. In order to obtain a clear view on the
      current situation, we made a review on all the cases of midtrimester induced
      abortion in Maternity University Hospital 'Maichin dom' for the year of 2012. We
      found that the mid trimester abortions represent 11.7% of all abortions performed
      in the hospital in 2012. Most widely used are the following methods: vaginal
      application of prostaglandin E2 vag. tabl. 3 mg--33.5%, intrauterine balloon
      catheter application after priming of the cervix with prostaglandin E2 3 mg--18%,
      prostaglandin F 2alpha as intrauterine extraamniotic continuous infusion through
      a balloon catheter, noweighton--9%, vaginal application of Prostaglandin E1-
      5.4%. Surgical termination was used in as little as 6% of the cases. The shortest
      interval for expulsion had been registered with the application of PG E1--19'55",
      compared with the most widely spread method of application of PG E2, which was
      more than twice longer--42'12". Application of balloon catheter, after priming of
      the cervix with 3 mg PG E2 vag. tabl. proved to be inefficient with mean interval
      for expulsion of 88'42". Surgical termination for midtrimester pregnancy is seen
      as the last alternative, it is rarely applied and mostly as anurgent procedure.
      In conclusion, the existing regimes for medical termination of midtrimester
      pregnancy are inefficient; application of 3 mg PG E2 is ineffective during the
      second trimester, insertion of balloon catheter attached to a weight is
      unacceptable. It is highly recommended that more attention is paid to the
      surgical termination with regards to residence training programmes and
      maintaining of qualification. This is needed as the procedure is usually
      performed to stop life threatening bleeding and is hence urgent. We underline the
      necessity of adequate guidelines for midtrimester medical termination. They
      should be based on Misoprostol as this is the gold standard for this gestational
      age. We believe there is enough clinical and scientific evidence for its safety
      and efficacy. Moreover, we are happy to announce that Misoprostol is already
      registered in Bulgaria.

PMID- 24294761
TI  - [Induced labor in cases of intrauterine growth retardation].

PMID- 24294762
TI  - [Periodontal disease and preterm birth].
AB  - Preterm birth (PB) is a primary public health challenge in both developed and
      underdeveloped nations. Despite improvements in obstetric care, rates of preterm
      birth have not decreased during the last 10 years. The etiological role of
      maternal infection, either in the genital tract or elsewhere, on preterm delivery
      remains unclear. Periodontal disease (PD) is one of the most common chronic
      infectious diseases. This type of infection is caused primarily by Gram-negative
      anaerobic, and microaerophilic bacteria that colonize the subgingival area and
      produce significant amounts of proinflammatory cytokines, mainly interleukin 1
      beta and interleukin 6, prostaglandin E2, and Tumor necrosis factor alpha. PD may
      therefore influence PB through an indirect mechanism involving inflammatory
      mediators or through a direct bacterial assault on the amnion.

PMID- 24294763
TI  - [Potential for diagnosis in preeclampsia].
AB  - Preeclampsia (PE) is characterized with hypertension and proteinuria after 20
      gestational weeks and is the major reason for maternal and fetal mortality during
      pregnancy. Etiology of PE is still unclear. Cliniical manifestation is connected
      to high levels of circulated anti-angiogenic proteins such as soluble Fms-,like
      tyrosine kinase 1 (sFlt1) and soluble endolgin (sEng). Furthermore PE leads to
      low serum levels of Placental growth factor (PIGF). The change of these serum
      levels appears before clinical manifestation, which makes them useful for
      screening of pregnant women with high risk of PE. This opportunity for prediction
      of PE would significantly lower the mortality caused by PE. We measure serum sFlt
      1 and PIGF levels in pregnant women with normal and pathological pregnancy,
      including gestational and chronic hypertension without PE. Population included 40
      pregnant women during a period of two years. Comparison between the groups was
      made with parametric Student's test. A level of p < 0.05 was accepted as
      statistically significant. Ten women were with PE. Fifteen pregnant women were
      with chronic kidney disease without hypertension. Fifteen pregnant women were
      with normal pregnancy (control group). Serum sFlt-1 and PIGF levels showed
      significant differences in pregnant women with PE compared to control group and
      CKD patients: a) for sFlt-1--in PE (4971.25 pg/ml) and normal pregnancy (3125.53
      pg/ml)--p < 0.005 or CKD (3145.80 pg/ml)--p = 0.0032 and b) for PIGF--in PE
      (206.63 pg/ml) and normal pregnancy (667.87 pg/ml)--p = 0.0011 or CKD (643.13
      pg/ml)--p = 0.003. Our study shows that angiogenic factors may aid in
      differentiating between PE caused by angiogenic imbalance and by renal function
      worsening.

PMID- 24294764
TI  - [Our and foreign experience in diagnosis and treatment of preeclampsia].
AB  - AIM: Our aim was to evaluate our experience in diagnosis and treatment of
      preeclampsia in the clinic of Pathological pregnancy--Varna Medical University.
      We compared our results with the results of prominent western clinics. MATERIAL
      AND METHODS: We evaluated 140 patients with preeclampsia for the period of 2010
      to 2013. A special file was fulfilled. It included: age, parity, gestational age,
      value of arterial blood pressure, urea, creatinine, common protein in blood,
      duration of treatment, oedema, urine protein. RESULTS: The mean age of the
      patients was 30 years. The urea and creatinine were normal. The mean hospital
      stay was 5,71 days. The blood protein was 61 g/l, only 4.17% of the patients were
      with protein lower than 58 g/l. In 87.5% of the patients the systolic blood
      pressure was between 135 and 160 mmHg, in 12.5% the systolic blood pressure was
      over 160mm Hg. In 58.34% there was a proteinuria. The mean gestational age was 33
      gestational weeks. The delivery was performed in the most suitable for the
      preeclampsia gestational age. CONCLUSIONS: According to our research work the
      patients with preeclampsia have a very high risk for cardio-vessel diseases and
      again of preeclampsia in their future pregnancies from 30%-40%. High prenatal
      care can prevent most of the complications connected with this disease.

PMID- 24294765
TI  - [The probiotics effectiveness in the therapy of inflammatory bowel diseases].

PMID- 24294766
TI  - [Endoscopic diagnostics of colorectal endometriosis].
AB  - The purpose of the study is to explore and systematize the endoscopic features of
      colorectal endometriosis and to evaluate the role of colonoscopy in its
      diagnosis. MATERIAL AND METHODS: Were analyzed 320 diagnostic colonoscopies
      performed during the period from March 2011 till November 2012 in patients
      admitted to the hospital with a diagnosis of "infiltrative form of external
      endometriosis". RESULTS: Among all the identified cases of intestinal
      endometriosis (n = 67) pathological process was localized more often in the upper
      section of the rectum ampullar - 38 (56.7%), less often were revealed lesions of
      lower ampullar section of rectum and anal canal in 5 (7.4%). In 6 (8.9%) cases
      were detected multifocal lesions of the intestine. Authentic signs of colorectal
      endometriosis were detected in lesions of the mucous membrane. These include:
      polypoid growths above the endometriosis lesion (15 (22.4%)), endometrioid
      heterotopias in the colon mucosa (7 (10.4%)), the presence of ulceration of the
      mucous membrane in the projection of endometriosis (4 (5.9%)) geoidal mucosa (3
      (4.5%)). Colorectal endometriosis can be systematized according to the following
      endoscopic criteria: localization of the pathological focus, growth, the presence
      of mucosal lesions.

PMID- 24294767
TI  - [The composition of the gastrointestinal mucosa-associated microbiota in
      irritable bowel syndrome patients].
AB  - THE AIM OF THIS STUDY: To investigate and analyse the gastrointestinal mucosal
      associated microbiota in the samples from diarrhea-predominant IBS (D-IBS),
      constipation--predominant IBS (C-IBS) patients and healthy controls. METHODS:
      Oral cavity, duodenal, colonic and rectal mucosal samples were obtained from 40
      IBS patients (20 C-IBS, 20 D-IBS) and 14 healthy controls. Duodenal and colonic
      tissue was collected during a flexible duodenoscopy and colonoscopy. Tissue
      samples were frozen for further molecular analysis. DNA was extracted from all
      frozen samples and used to identify 29 specific bacterial groups using
      quantitative real-time PCR (qPCR). A statistical treatment of the received data
      was performed. RESULTS: The dominant groups of bacteria of various microbiotops
      of the gastrointestinal tract in IBS patients and healthy controls were
      determined. qPCR analysis of duodenal samples demonstrated a reduction in the
      Bifidobacterium concentration in tissue samples from C-IBS patients when compared
      to healthy controls (p < 0.05). Analysis of rectal samples demonstrated an
      increase in concentrations of Faecalibacterium praustnizi (p < 0.05) and a
      reduction in the concentration of Streptococcus spp. (p < 0.01), Atopobium
      claster (p < 0.05), Ralstonia spp.+Burkholderia spp (p < 0.05) in tissue samples
      from D-IBS and C-IBS patients when compared to healthy controls. CONCLUSIONS: Our
      molecular data indicate that quantitative differences exist in specific bacterial
      groups in the microbiota between IBS and healthy subjects. The concentration of
      representatives of Bacteroidetes phylotypes appeared to be the most stable in
      various microbiotops of the gastrointestinal tract. Small intestinal bacterial
      overgrowth in IBS patients was not found. Received data help to suggest
      correlation with the features of the microbiota with clinical form of IBS.

PMID- 24294768
TI  - [Clinical and morphological variants of diverticular disease in colon].
AB  - Our own results of two-stage research are presented in the article. The first
      stage contains the retrospective analysis of 3682 X-ray examining of large bowel
      which were conducted in 2002-2004 to define the structure of colon disease and to
      determine gender differences. The second stage is prospective research which took
      place from 2003 to 2012 and 486 patients with diverticular disease were regularly
      observed. Following parameters were estimated: dynamics of complaints, life
      quality, clinical symptoms. Multiple X-ray and endoscopic examining were done
      with estimation of quantity and size of diverticula, changes of colon mucosa,
      comparison of X-ray and endoscopic methods in prognosis of complications. Two
      basic clinical morphological variants of diverticular disease (DD) of colon are
      made out as a result of our research. There are IBD-like and DD with ischemic
      component. The variants differ by pain characteristics, presence of accompanying
      diseases, life quality parameters and description of colon mucosa morphological
      research. We suppose that different ethiopathogenetic factors of development of
      both variants mentioned above influence the disease prognosis and selection of
      treatment.

PMID- 24294769
TI  - [Cell adhesion molecules in evaluation of Crohn's disease therapy].
AB  - The treatment of inflammatory bowel diseases (IBD), which include ulcerative
      colitis (UC) and Crohn's disease (CD) is one of actual problems of modern
      gastroenterology and coloproctology. In recent years a great attention is paid to
      the molecules of adhesion. Adhesion proteins play a significant role in the
      development of inflammation in patients with IBD. They cause the migration of
      cells from the capillaries into the center of inflammation, i.e. do much to
      increase the inflammatory infiltration of the mucosa and homing of lymphocytes.
      Changes in the levels of adhesion factors under the influence of biological
      therapy have been insufficiently studied. So the aim of our study was to
      determine the diagnostic value of adhesion molecules--integrin-sVCAM-1 and
      selectins P-, E-, L- for the assessment of the effectiveness of therapy in
      patients with UC and CD and prognosis of the disease. 15 patients with IBD were
      examined (15 patients with Crohn's disease (CD)). 9 patients were treated using
      infliximab 5 mg/kg according to the standard scheme (0-2-6 and then every 8
      weeks). 3 patients with IBD received anti-inflammatory therapy with the
      introduction of the culture of MSC in the number of 150 x 108 cells suspended in
      200 ml of physiological solution with the addition of heparin (10 IU/ml). 3
      patients received azathioprine (2 mg/kg) and glucocorticosteroids (GCS) 1 mg/kg.
      The clinical symptoms, the level of leukocytes, erythrocyte sedimentation rate, C
      reactive protein and also were analyzed before and after the treatment with
      infliximab and transplantation of MSC. The status of the colonic mucosa was
      evaluated using colonoscopy with biopsy. The concentration of adhesion molecules
      L-selectin, E-selectin, P-selectin, integrin-sVCAM-1 in blood serum was analyzed
      using immunoenzyme method twice before the beginning of treatment and after 2
      months. It is established that after the standard therapy with the use of
      corticosteroids and azathioprine clinical and laboratory signs of IBD activity
      and increased levels of adhesion molecules remained in all patients. It is
      reliably determined that under the influence of infliximab the levels of P
      selectin, E-selectin and integrin-sVCAM-1 decrease to 8.9 +/- 1.0 ng/ml, 5.5 +/-
      1.7 ng/ml, 9.5 +/- 4.4 ng/ml, respectively (p < 0.001) in all patients with IBD.
      This point to the suppression of the synthesis of the main inflammatory cytokine
      alpha-TNF. Transplantation of MSC causes significant decrease of P-selectin, E
      selectin to 6.9 +/- 1.1 ng/ml and 5.7 +/- 1.3 ng/ml, respectively (p < 0.001).
      Integrin-sVCAM-1 has decreased slightly to 12.2 +/- 2.2 ng/ml, p > 0.1. This is
      associated with the onset of the maximum therapeutic effect only in 1-2 months
      after transplantation. The levels of P-selectin, E-selectin, integrin-sVCAM-1,
      reflecting the acute phase of inflammation, decreased after MSC transplantation
      and infliximab induction therapy. The level of L-selectin, reflecting a chronic
      autoimmune inflammation, practically does not decrease after the MSC
      transplantation (8.9 +/- 0.5 ng/ml, p < 0.05) and infliximab induction therapy
      (9.6 +/- 0.8 ng/ml, p > 0.1). These include the appointment of long-term
      infliximab therapy and repeated MSC transplantations. P-selectin, E-selectin, L
      selectin, integrin-sVCAM-1 are modern markers of inflammation and may be used to
      assess the effectiveness of standard and biological therapy in patients with IBD,
      and to predict the course of the disease.

PMID- 24294770
TI  - [Inflammatory nature of colon diverticula].
AB  - On the basis of morphological and immunological study of biopsies of the colon in
      patients with diverticulosis was revealed that microscopic inflammation of the
      mouth of the diverticulum is characterized by several features that include
      excessive proliferation of the epithelium, the predominance of macrophage
      reaction in the development of the immune response, increased cell adhesion and
      unusual ratio between the expression of cytokines and other regulatory molecules.
      Changes in the structure of the formed diverticula tissue are associated with
      dysregulation of many processes of tissue metabolism and morphogenesis. These
      include the dysregulation of cell renewal of the epithelium (increased level of
      proliferation of epithelial cells and inhibition of apoptosis), degradation of
      extracellular matrix components, moderate vascular reaction. All these processes
      take place on the background a particular form of immune protection and
      adaptation mechanisms.

PMID- 24294771
TI  - [Antibodies to Saccharomyces cerevisiae as predictors of the complicated flow of
      Crohn disease].
AB  - Among the 143 patients in the acute phase of IBD the ASCA detected in 34 people,
      accounting for 23.8%, and in 60 patients with CD the increased level of ASCA was
      found in 24 people (40%), in 83 patients with UC the increased level of ASCA was
      found in 9 (10, 8%). The appearance of antibodies to Saccharomyces cerevisiae in
      the blood serum of patients with CD is regarded as a prognostically unfavorable
      sign, indicating that the disease may have a complicated course. Also, high
      titers of ASCA combined with complicated CD, requiring surgical treatment.

PMID- 24294772
TI  - [Tacrolimus in perianal manifestations of Crohn's disease].

PMID- 24294773
TI  - [Inflammatory bowel disease and possible applications of tumor necrosis factor
      inhibitors in pregnant women].

PMID- 24294774
TI  - [Role of rifaximin in correction of IBS-like symptoms in patients with
      inflammatory bowel disease].
AB  - One of the important problems in the treatment of patients with inflammatory
      bowel disease are the persistent complaints of pain, abdominal distention,
      frequent stools, excretion of mucus with faeces with the presence of endoscopic
      or roentgenologic remission in the damaged parts of gastrointestinal tract. In
      this review we describe possible causes of such complaints and some methods of
      their therapeutic correction.

PMID- 24294775
TI  - [Leiomyoma of the small intestine as a cause of acute intestinal obstruction].

PMID- 24294776
TI  - [The 8th Congress of ECCO, 14-16 February 2013. Vienna, Austria].

PMID- 24294777
TI  - [Cross-autoimmune syndromes in hepatology].
AB  - Along with the traditional autoimmune liver diseases--autoimmune hepatitis (AIH),
      primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)--in
      clinical practice there are syndromes of autoimmune decussating. The term cross
      syndrome means that in one patient there are signs of two different autoimmune
      liver diseases, that probably have a common pathogenesis. In line with the
      literature data and own experience of the diagnostic criteria there are different
      cross-syndromes: AIH and PBC, AIH and PSC; and also a combination of AIH and
      chronic hepatitis C. The most appropriate combinations and doses of prednisolone
      (budesonid), azathioprine and ursodesoxycholic acid, recommended for treatment of
      various options of cross-syndrome, as well as medical tactics in view of the
      conjunction of AIH and chronic hepatitis C, have been considered.

PMID- 24294778
TI  - [Pathogenetic importance of proinflammatory cytokines in the formation and
      progression of fibrosis in alcoholic hepatitis].
AB  - AIM OF INVESTIGATION: To study the effect of tumor necrosis factor alpha (TNF
      alpha) and interleukin 6 (IL-6) on prognosis and outcome of alcoholic hepatitis
      (formation of fibrosis). METHODS: Overall 48 patients with alcoholic hepatitis
      (AH) were investigated. The control group consisted of 25 healthy donors.
      Morphological study of liver biopsies and 13C-methacetin breath test (13C MBT)
      was carried out at 15 patients with AH. Concentration of TNF-alpha, IL-6 and C
      reactive protein (CRP) in blood serum was detected by immunoenzyme assay with
      application of commercial tests-systems Vector-Best. STUDY RESULTS: At patients
      with AH TNF-alpha, IL-6 and CRP significantly increased in comparison to healthy
      persons. We found a significant correlation between fibrosis stage and TNF-alpha
      (r = 0.53; p < 0.01), IL-6 (r = 0.62; p < 0.01), the Knodell Histological
      Activity Index and TNF-alpha (r = 0.58, p < 0.05), IL-6 (r = 0.64; p < 0.01), the
      results of 13C MBT and TNF-alpha (r = -0.72; p < 0.01), IL-6 (r = -0.73; p <
      0.01), alanine aminotransferase and TNF-alpha (r = 0.61; p < 0.01), IL-6 (r =
      0.54; p < 0.01), aspartate aminotransferase and TNF-alpha (r = 0.64; p < 0.01),
      IL-6 (r = 0.65; p < 0.01), gamma-glutamyl transpeptidase and TNF-alpha (r = 0.46;
      p < 0.01), IL-6 (r = 0.48; p < 0.01). CONCLUSIONS: Serum TNF-alpha and IL-6 have
      predictive value for development of inflammation and fibrosis in patients with AH
      and can be used as non-invasive markers of fibrosis.

PMID- 24294779
TI  - [About the prevalence of diseases of pancreas in the Udmurt Republic].
AB  - THE AIM OF OUR INVESTIGATION: To study the dynamic of morbidity level of pancreas
      in Udmurt Republic (UR) and to prognose it for nearest years. MATERIALS AND
      METHODS: We used the official statistic materials of Republic medical information
      analytic center for 2001-2011 yy. In analyses of received data we used trend
      models and statistic method. THE RESULTS: We found that during analyzing period
      (2001-2011) common morbidity of pancreas in UR increased as well as primary--on
      246% and 92% correspondently, especially in rural population. Morbidity of adult
      urban population is significantly higher than. By trend model method we can
      prognose raising of pancreas for nearest 5 years till the level of Russian one
      and higher. CONCLUSION: The tendency to increasing of pancreas diseases morbidity
      in UR was revealed for last 10 years. Prognosing rise of morbidity, more in rural
      population, requires to organize active prophylactic measures.

PMID- 24294780
TI  - [Cholelithiasis and cholesterosis of a gallbladder: a comparison of pheno
      genetypic characteristics of patients].
AB  - A study was and comparison was carried out of the phenotypical and genotypical
      features in 115 patients with cholelythiasis and 97 patients with cholesterosis
      of the gallbladder. The received data proves that cholelythiasis is characterized
      by the domination of (prevalence) of type O I blood type, decrease of blood types
      B III and AB IV in comparison to the control group and to the group with
      cholesterosis of the gallbladder (p < 0.05), increase of the frequency of gene O
      decrease of frequency of gene B, decrease of heterozygosis. Patients with
      cholesterosis of the gallbladder are characterized by the increase of frequency
      of gene A, decrease of ratio of patients with blood type B III and increase of
      patients with AB IV blood type (p < 0.05). The received data (results) show the
      presence of different and multidirectional phenotypical and genotypical
      characteristics in patients with cholelythiasis and cholesterosis of the
      gallbladder, and therefore differ genotypically.

PMID- 24294781
TI  - [The association of indicators of serum lipids and bile in individuals with the
      family history, burdened by a bile stone disease].
AB  - PURPOSE: To evaluate serum and bile lipids levels in persons with and without
      positive family history of gallstone disease (PFH GSD). MATERIALS AND METHODS:
      165 people were surveyed: 71 people with PFH GSD and 94 persons without PFH GSD.
      was evaluated: in serum--total cholesterol--TCh, triglycerides--TG, HDL, in the
      gallbladder bile--cholesterol (BCh), total bile acids (TBA), TBA/BCh coefficient
      (TBC), sialic (SA) and cholic acid (CA). RESULTS: TCh (5.3 +/- 0.13 mmol/L), TG
      (2.1 +/- 0.13 mmol/L) blood serum levels and BCh (3.6 +/- 0.2 g/l) were higher in
      persons with PFH GSD than in those without PFH GSD (4.8 +/- 0.1; 1.2 +/- 0.09 and
      2.8 +/- 0.2, respectively), and HDL (1.0 +/- 0.04 mmol/L) and TBC levels (6.9 +/-
      0.5 Units) in persons with PFH GSD were lower than in those without PFH GSD (1.5
      +/- 0.03 and 9.3 +/- 0.8, respectively), p < 0.05 in all cases. TBA, SA and CA
      levels did not differ between two groups. CONCLUSION: PFH GSD was associated with
      blood serum lipid profile (total cholesterol, triglycerides, HDL) and the
      composition of bile (bile cholesterol, TBA/BCh coefficient).

PMID- 24294782
TI  - [Diagnostics of non-erosive gastroesophageal reflux disease with the use of new
      digital endoscopic techniques].
AB  - As gastroesophageal reflux disease is a "disease of the XXI century", the
      relevance of its diagnosis at early stages is high. Using transnasal
      esophagogastroduodenoscopy, which is significantly better tolerated by patients,
      and the technology of intelligent color coding of pathology of the mucous
      membrane FICE, can diagnose the earliest manifestations of GERD in the form of
      inflammatory noerosive changes in the mucous membrane of the distal esophagus, to
      evaluate the failure of the lower esophageal sphincter; to make a prognosis for
      the disease, and to formulate a rational policy of conducting the patient.

PMID- 24294783
TI  - [Acute hepatitis in infectious diseases].
AB  - Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis,
      however, there are many infectious diseases affecting liver and with fever, early
      diagnostics of which is very important for the clinic of internal diseases. This
      review presents infections, causing fever and hepatitis, but not necessarily
      accompanied by jaundice. Leptospirosis, yellow fever have been considered, in
      which liver damage determines the clinic and the prognosis of the disease. In
      other cases, such as infectious mononucleosis, cytomegalovirus and herpetic
      hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral
      diseases, malaria, Legionnaire's disease, hepatitis do not have their independent
      status and represent one of the important syndromes of a common disease. Modern
      methods of diagnostics and treatment of these diseases have been described.

PMID- 24294784
TI  - [Syndrome of endogenous intoxication in the pathogenesis of viral hepatitis].
AB  - This paper presents a review of the literature on the mechanisms of development
      the syndrome of endogenous intoxication. Given the different definitions the
      syndrome of endogenous intoxication, the phase of pathogenesis, the basic
      mechanisms of its development. The characteristic of endotoxic substances, their
      effects on the body as a whole and on the organs of detoxification, in
      particular. It is shown that the main role of the liver to detoxify the body and
      its functions in violation of the incidence of virus hepatitis. The methods of
      diagnosis of the syndrome of endogenous intoxication.

PMID- 24294785
TI  - [The transport component of the secretory activity of pancreas].
AB  - The transport processes take place on the all stages of pancreatic secretion. The
      article highlighted the multi-parametric regulated exosecret transport through
      the duct system of the pancreas. The system has valves and micro-reservoirs of
      secret. A disturbance of their motor coordination leads to the main cause of
      acute pancreatitis.

PMID- 24294786
TI  - [Overview of international recommendations on approaches a view of a physician
      and surgeon].
AB  - In different countries a set of recommendations for the diagnostics and treatment
      of chronic pancreatitis (CP) have been published, but to date a unified
      systematic management has not been developed yet. Because CP is within the
      interests of physicians of various specialties: surgeons, gastroenterologists,
      endoscopists and others, approaches to the most effective treatment--conservative
      therapy, endoscopic or surgical treatment--should be determined on an equal
      footing on the basis of well-known and well-conducted trials at the minimization
      of possible interpretations of the terms and tactics. In most cases there is a
      need for a comprehensive approach, which allows to achieve the main tasks: to cut
      pain short, maintain the function of the gland and/or compensate for pancreatic
      insufficiency, eliminate or prevent the development of complications, using a
      combination of the most effective methods of treatment. The opinion of all
      involved in the fate of particular patient specialists in the absence of common
      international standards, must be based on the results of the research evidence.
      The purpose of this review is to analyze the scientific studies in this field
      with a focus on existing practical guide of pancreatilogical associations of
      different countries of the world. Formulated during the analysis, the conclusions
      and provisions on the basis of strict methodological approach can be useful for
      Russian gastroenterologists, surgeons and general practitioners.

PMID- 24294787
TI  - [Simulation of the interaction of gastroenterologists, endoscopists and surgeons,
      as the present and the future of high-tech gastroenterology of Chuvashia].
AB  - The analysis of the joint work of gastroenterologists, surgeons and endoscopists
      Republican gastroenterological center of the Chuvash Republic. The importance of
      creating a model of interaction of gastroenterologists, surgeons and endoscopists
      for the development of high-tech gastroenterology in the Chuvash Republic.

PMID- 24294788
TI  - [Correction of indigestion in chronic biliary pancreatitis].
AB  - Chronic pancreatitis (CP) is one of the most urgent and investigated problems in
      gastroenterology. Despite the variety of the spectrum of etiologic, pathogenetic
      and provoking factors for CP, one of the leading causes of disease pathology is
      pathology of biliary tract. A key element in the treatment of CP is a correction
      of the digestive system, with biliary pancreatitis feature that distinguishes it
      from other forms of pancreatitis, is a combination of exocrine pancreatic
      insufficiency with chronic biliary insufficiency. The variety of biochemical and
      immunological effects of ursodeoxycholic acid (UDCA) can treat it with biliary
      pancreatitis as the drug of etiological, pathogenetic and substitution therapy.
      UDCA (Ursosan) in combination with modern mini-microspheroidal polyfermental
      drugs significantly improves the clinical efficacy of the correction of the
      digestive system in biliary pancreatitis.

PMID- 24294789
TI  - [Drug safety in gastroenterology].
AB  - Drug safety is one of the priorities of modern medicine and pharmacy. In modern
      gastroenterology drug safety issues due to a number of reasons even more relevant
      than in other branches of medicine. The major areas of drug ensure patient safety
      in the practice of gastroenterologists, as well as other doctors, are: 1) direct
      involvement of practitioners in the system of pharmacovigilance, 2) used in the
      practice of clinical research and evidence-based medicine, 3) the use of the
      principles of rational pharmacotherapy.

PMID- 24294790
TI  - [The use of endoscopic techniques in acute strangulated adhesive small bowel
      obstruction, proceeded under the guise of acute pancreatitis].
AB  - We report an unusual case of AASBO presenting like postcholecystectomy syndrome
      and acute pancreatitis. Diagnostic and therapeutic scope of laparoscopic
      interventions and endoscopic nasointestinal decompression in AASBO management is
      demonstrated.

PMID- 24294791
TI  - [Gluttony, obesity and the metabolic syndrome in the context of the "seven deadly
      sins". Historical-theological, literary and art, mass media, political,
      philosophical, medical-psychological and geriatric aspects of the problem].
AB  - In this pape different aspects of problem of obesity are analysed.

PMID- 24294792
TI  - [Kislovodsk is not only a resort-city. A report from the scientific forum].

PMID- 24294793
TI  - [2nd "European Days on Colorectal Cancer"].

PMID- 24294794
TI  - Pre-operative irradiation for retroperitoneal liposarcoma: results of a pilot
      study.
AB  - PURPOSE: The aim of this study was to evaluate toxicity and benefit of an
      original method of preoperative irradiation combined with adequate surgery in the
      treatment of retroperitoneal liposarcoma. Instead of irradiating the whole tumor
      volume, 50Gy in 25 fractions was delivered to the posterior part of the tumor and
      the contact zone with the postero-lateral abdominal wall only. METHODS: Between
      mid-2000 and end of 2011, 29 patients were included in this study, 22 with a
      primary tumor, 7 with a first local recurrence. The results obtained were
      compared with a well-matched control group operated on by the same surgeon during
      the same period. RESULTS: This therapy was well tolerated by all included
      patients and no difference in toxicity was found between pilot and control group.
      With a median follow-up of 84 months the oncological results were similar in both
      groups with a 5 y disease specific survival of 79 and 81% (p: 0.61). However a
      very significant difference was found according to histotype: five year disease
      specific survival was 84% (CI 66-93) for the well- differentiated and only 35%
      (CI 20-51) for the dedifferentiated liposarcoma (p < 0.0001). CONCLUSIONS: This
      form of combined treatment is well tolerated but superiority could not be
      demonstrated. Our experience clarifies some of the difficulties facing a
      randomized clinical trial on this topic.

PMID- 24294795
TI  - Anal stretch plus fissurectomy for chronic anal fissure.
AB  - INTRODUCTION: Anal fissure is a common disease. Usually chronic anal fissures are
      managed medically. When conservative management fails, surgical treatment should
      be considered. Lateral internal sphincterotomy has been advocated as the first
      choice invasive treatment but it has a reported rate of major fecal incontinence
      of 5%. In order to reduce the onset of major fecal incontinence after anal
      fissure surgery, it has been proposed to use the anal stretching plus
      fissurectomy. METHODS: From 2008 to 2011, 457 patients have been operated for
      chronic anal fissure. RESULTS: Twenty-seven patients underwent lateral internal
      sphincterotomy, two patients underwent posterior sphincterotomy and 428 patients
      underwent anal stretch plus fissurectomy. Satisfactory results have been reported
      in 95% of the cases. Transient incontinence rates have been of 3% after anal
      stretch and of 14.8% after lateral internal sphincterotomy (p < 0.05). Major and
      persistent incontinence rates have been reported in a case after later internal
      sphincterotomy (3%) but never after anal stretching (p = 0.059). Recurrence
      occurred in 2% of the patients after anal stretch and in 3% of the cases after
      lateral internal sphincterotomy (p = ns). CONCLUSION: Lateral internal
      sphincterotomy and anal stretch have nearly a reported 95% of good results but
      the first have 3-5% rates of major incontinence.

PMID- 24294796
TI  - Histopathological, histogenetic, and immunohistochemical analysis of epidermoid
      cyst of spleen.
AB  - Splenic cysts are encountered not uncommonly, but large cysts occupying a
      significant portion of the spleen are extremely rare. We report a case of a young
      female patient presenting with a large epidermoid cyst involving the majority of
      the spleen. The patient was involved in a motor vehicle accident during which she
      sustained multiple rib fractures and traumatic internal organ injuries. She
      subsequently underwent exploratory laparotomy and splenectomy for grade III
      splenic lacerations. Incidentally, a 13.3 cm in greatest dimension splenic cyst
      replacing the majority of the splenic parenchyma was identified. Grossly, the
      inner lining of cyst was gray-white, smooth, and glistening. Histologically, the
      thick fibrous cyst wall was composed of stratified squamous epithelium, scattered
      foci of which were denuded. A panel of properly-controlled immunohistochemical
      stains was performed and showed the squamous epithelium to be strongly and
      diffusely immunoreactive with carcinoembryonic antigen (CEA), CA 19-9, and
      cytokeratin 5/6, focally immunoreactive with HBME-1, and negative for calretinin.
      The histomorphological features and immunohistochemical staining pattern were
      consistent with a diagnosis of an epidermoid cyst of the spleen.

PMID- 24294797
TI  - Meta-analysis of temporary ileostomy versus colostomy for colorectal anastomoses.
AB  - BACKGROUND/AIMS: Defunctioning stoma is a common surgical procedure, it is now
      generally acknowledged that defunctioning stoma significantly reduce the rates of
      complications in colorectal surgery, but the choice of temporary ileostomy or
      temporary colostomy for defunctioning colorectal anastomoses remains
      controversial. This meta-analysis evaluated two types of defunctioning stoma to
      determine whether one is superior to the other. METHODOLOGY: Studies and relevant
      literatures comparing temporary ileostomy with temporary colostomy for
      defunctioning colorectal anastomoses were searched though PubMed, Embase and The
      Cochrane Library. The rates of complications were pooled and compared using a
      meta-analysis. The risk ratios were calculated with 95% confidence intervals to
      evaluate the safety and efficacy of each technique. RESULTS: Five randomized
      controlled trials and seven non-randomized studies were included, with 1687
      patients in total. The meta-analysis of the RCTs demonstrated a lower risk of
      stoma prolapse (RR 0.15; 95% CI: 0.04-0.48, p = 0.001) in the temporary ileostomy
      group. Meta-analysis of the non-randomized studies showed a lower risk of stoma
      prolapse (RR 0.26; 95% CI 0.10-0.67, p = 0.005) and wound infection after stoma
      closure (RR 0.28; 95% CI 0.5-0.52, p < 0.0001) in the temporary ileostomy group.
      No other statistically significant difference was observed for complications.
      CONCLUSIONS: Each type of defunctioning stoma has its advantages and
      disadvantages, and there is not a strong evidence for the superiority of one
      temporary stoma over another for colorectal anastomoses. According to this, large
      scale RCTs and high quality studies are needed to conduct.

PMID- 24294798
TI  - Pre-school children with hydatid lung disease.
AB  - BACKGROUND: Hydatid cyst disease is a major health problem in developing
      countries and it usually settles in the lungs in children. This study aimed to
      present pre-school children with lung hydatid cysts cases that underwent surgical
      treatment. METHODS: The authors retrospectively investigated 42 consecutive pre
      school patients who were diagnosed and surgical treated for hydatid cysts in
      their clinic between January 1998 and December 2011. RESULTS: Seventeen (40.5%)
      patients were female and 25 (59.5%) patients were male. The average age of the
      patients was 5.2 +/- 1.3 (between 2-7 years). The most common symptoms were cough
      (74%), chest pain (26.2%), and fever (26.2%). Twenty-eight cases had cysts in
      only one lung; in five cases, the cysts were in a single lung and the liver, in
      six cases, in bilateral lungs and liver, and in three cases, in bilateral lungs.
      The average cyst diameter was 6.2 +/- 2.4 (2-12) cm. In five cases, there were
      combined interventions to the right lung and liver cysts with a
      transdiaphragmatic approach. Nine patients with bilateral hydatid cysts underwent
      operations. Muscle protector thoracotomies were performed in eight cases.
      Cystotomy and capitonnage were applied to all lung cysts. One patient underwent a
      bronchoscopy for postoperative atelectasis. In one case, postoperative fever was
      observed. There was no postoperative mortality. Postoperative average hospital
      stay was 7.2 +/- 2.1 (3-13) days. CONCLUSION: Surgery is the definitive treatment
      for lung hydatid cysts. The most important way to protect against the adverse
      effects of a thoracotomy is to eliminate the routes of transmission.

PMID- 24294799
TI  - Pancreaticoduodenectomy for advanced gastric carcinoma patients.
AB  - OBJECTIVE: The prognosis for patients with gastric carcinoma that has invaded
      adjacent organs, especially the pancreas, is very poor. We evaluated the survival
      of patients following pancreaticoduodenectomy (PD) and the survival benefit of
      intravenous chemotherapy in these patients. METHODS: We reviewed the hospital
      records of 16 gastric carcinoma patients who underwent PD during the period from
      2001 to 2005. RESULTS: Half of the patients undergoing PD had Borrmann type III
      gastric carcinoma (8/16; 50%). Using Cox's proportional hazards regression model,
      only one factor was identified as an independent, statistically significant
      prognosticator intravenous chemotherapy (risk ratio, 0.054; 95% confidence
      interval, 0.01-0.45; p < 0.01). The 5-year survival rate was higher for patients
      who had intravenous chemotherapy than for patients who did not (22.2% vs. 0%; p <
      0.01). CONCLUSION: The results highlight the improved survivorship of gastric
      carcinoma patients with PD who received intravenous chemotherapy compared with
      those who did not. We recommend resection in these patients and the
      administration of intravenous chemotherapy to improve their survival.

PMID- 24294800
TI  - Retroperitoneal schwannoma. A complex surgical treatment of a tumor with
      uncertain behavior.
AB  - BACKGROUND: Retroperitoneal schwannoma is a rare nerve sheath tumor; the surgical
      removal of this tumor is sometimes compromised by its location. The aim of this
      study is to analyze our experience with the diagnosis and treatment of this type
      of tumor. METHOD: We present our experience between 1999 and 2011 in the
      diagnosis and treatment of retroperitoneal schwannoma. During that time, we
      diagnosed and treated five female patients (four adults and one infant) with the
      condition. The tumors appeared sporadically and were not associated with
      neurofibromatosis or other syndromes. Diagnosis was performed by computed
      tomography (CT) imaging in four cases and by magnetic resonance imaging (MRI) in
      one case. RESULTS: All patients underwent surgical treatment and complete
      resection of the lesion. An open resection was performed in four cases, and in
      the most recent case, the excision was conducted laparoscopically. In all of the
      cases, the histological diagnosis was retroperitoneal schwannoma, and in one
      case, there was a melanocytic variant that was not associated with Carney
      syndrome. At the time of this report, there has been no evidence of recurrence.
      CONCLUSION: Retroperitoneal schwannoma is a tumor that is difficult to diagnose
      with imaging techniques, and because of its localization, the tumor is difficult
      to remove surgically.

PMID- 24294801
TI  - Prenatal detection of an enteric duplication cyst.
AB  - Enteric duplication cysts are rare congenital malformations of unknown aetiology.
      Because of improvements in prenatal ultrasound, more and more duplication cysts
      are found prenatally and treatment is started early. We describe a case of
      enteric duplication cyst diagnosed prenatally and resected soon after birth.
      Early diagnosis and prompt surgical treatment are the best way to prevent
      associated morbidity.

PMID- 24294802
TI  - Leiomyomatosis peritonealis disseminata associated with ascites and
      endometriosis: a case report and review of the literature.
AB  - We present a case of leiomyomatosis peritonealis disseminata (LPD) and review the
      literature. LPD is a rare, benign disorder that is characterized by multiple
      subperitoneal or peritoneal nodules of varying sizes on the omentum and
      peritoneal surfaces, grossly resembling disseminated carcinoma. It should be
      differentiated from other peritoneal tumors. It is mostly asymptomatic and
      diagnosis is often incidental during surgery. One should be aware of the
      iatrogenic component of this entity. LPD is being documented with increasing
      frequency. We report the case of a 39-year-old woman with chronic abdominal pain
      and heavy dysmenorrhea due to endometriosis associated with LPD. She underwent an
      abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. LPD
      and endometriosis is a known association. LPD with ascites and endometriosis
      however has not yet been reported.

PMID- 24294803
TI  - Granular cell tumor of the abdominal wall: case report and review of the
      literature.
AB  - Granular cell tumors (GCT's) are uncommon soft tissue neoplasms most likely of
      neural or neuroectodermal origin. They can be found in virtually any body site,
      but they are rarely located in the abdominal wall. We report the case of a
      patient with a history of breast cancer presenting with a slow-growing, firm and
      painless nodule in the abdominal wall. After ruling out metastatic origin of the
      mass by CT scan and MRI, an incisional biopsy was performed. Anatomopathologic
      findings were congruent with a benign granular cell tumor of the abdominal wall.
      En-bloc surgical resection with reconstruction of the abdominal wall defect using
      a prosthetic mesh was performed. Preoperative histopathologic diagnosis of an
      abdominal wall tumor is important. Broad surgical excision to obtain negative
      margins should be the therapeutic goal in all cases of GCT as positive margins
      are highly correlated with recurrence of the lesion.

PMID- 24294804
TI  - Spontaneous rupture of an aneurysm of the right subclavian artery as a first
      presentation of Ehlers Danlos syndrome in a 15-year old boy.
AB  - We report a case of a spontaneous rupture of a right subclavian aneurysm in a 15
      year-old patient. This ruptured aneurysm was successfully treated in an
      endovascular manner by placing a covered stent-graft in the right subclavian
      artery via right brachial access. Subsequent work-up by skin biopsy and
      fibroblast culture and by DNA-screening revealed the diagnosis of Ehlers Danlos
      type IV. Meanwhile, the patient developed twice a spontaneous pneumothorax,
      treated with thoracoscopic pleurodesis. This article provides a clear overview of
      the clinical and genetic characteristics of a case of Ehlers Danlos type IV and
      illustrates the importance of avoiding surgery in patients with connective tissue
      disease because of the high risk of perioperative complications.

PMID- 24294805
TI  - Radiotherapy-induced mitral incompetence.
AB  - Radiotherapy-induced cardiac disease is a progressive condition with symptoms
      beginning several years after treatment. The following article reports the case
      of a 48-year-old woman who had undergone mediastinal radiation therapy for
      Hodgkin's lymphoma at age of 15 and, more than thirty years later, suffered from
      congestive heart failure due to fibrotic thickening of the mitral valve. She
      successfully underwent mitral valve repair with patch augmentation of the
      anterior leaflet. Long-term cardiac follow-up of patients treated by mediastinal
      radiation therapy is warranted.

PMID- 24294806
TI  - Meso-Rex shunt using deep femoral vein conduit: first report.
AB  - The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al.
      for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric
      liver transplant patients. This technique provides more physiological relief of
      portal hypertension compared to the porto-systemic shunts, which can lead to long
      term complications such as hyperammonaemia and hepato-pulmonary syndrome.
      Different conduits as autologous and cryopreserved veins or prosthetic grafts
      have been previously reported. We present herein the first case of a MRS using
      the autologous deep femoral vein in a 17-year-old female patient affected by
      EHPVO from unknown reasons.

PMID- 24294807
TI  - Jean-Marie Baud (1776-1852). Professor at the Faculty of Medicine in two
      consecutive universities of Louvain.

PMID- 24294808
TI  - Syncope in elderly patients--is there a place for endomyocardial biopsy?
AB  - Syncope in the aging population has two characteristics--it always has a
      multifactorial origin and age by itself is a predictor of a worse outcome even in
      syncope with an apparent benign mechanism. Therefore, it is worthwhile
      investigating extensively the cardiac substrate in selected cases when the
      initial evaluation demonstrates its presence. In the cases where the usual workup
      fails to unveil the cause for the decompensating heart substrate, morphological
      examination with endomyocardial biopsy should be taken into account, after
      matching every particular case with one of the clinical scenarios listed in the
      Scientific Statement on the role of endomyocardial biopsy in the management of
      cardiovascular disease.

PMID- 24294809
TI  - "Don't worry, be happy"--may be a first line therapy in cardiovascular diseases?
AB  - Cardiovascular diseases represent the most frequent type of pathology nowadays.
      One can consider that their high prevalence is generated by an unhealthy living
      style, by the increasing prevalence of all kind of metabolic abnormalities, by
      smoking and other bad habits, but we must not forget the role of stress. The
      present paper highlights the fact that a pathophysiological link between stress,
      adverse affect and poor quality of sleep and cardiovascular diseases is
      represented by the sympathetic overdrive. As opposite, positive affect can offer
      a significant protection against pro-atherogenic effects that are generating a
      significant increase of the prevalence and severity of cardiovascular diseases.
      Finally, the present paper underlines the deleterious cardiovascular effects of
      antidepressive and antipsychotic drugs, so that the final conclusion is: "Don't
      worry, be happy" and have positive thoughts for a healthier future.

PMID- 24294810
TI  - The solitary kidney--a nephrological perspective.
AB  - The solitary kidney (SK) is of special interest for practitioners because of the
      reduced number of nephrons as compared to persons who have 2 kidneys. It
      undergoes adaptive phenomena of hypertrophy and hyperfiltration that allow long
      term evolution, but pathological situations might occur in the remnant kidney. In
      some persons with a SK, the adaptive phenomena can be associated with
      proteinuria, arterial hypertension (AH) and diminished Glomerular Filtration Rate
      (GFR). In very rare situations, diminution of renal function in patients with a
      SK can progress to end-stage renal disease (ESRD) and, totally exceptionally, it
      requires renal replacement therapy. The SK can be congenital or acquired. At
      present patients with a SK address themselves more and more frequently to
      nephrology services which monitor the evolution of both the congenital and the
      surgically acquired SK. The congenital SK possesses a higher number of nephrons
      (75%, as compared to 2 functional kidneys in a healthy person) than the
      surgically acquired SK - 50% nephrons. This makes adaptive phenomena differ.
      Secondary lesions sometimes appear later in case of the congenital SK. In other
      situations, no significant differences between the evolution of the congenital or
      acquired SK are registered. The congenital solitary kidney is often associated
      with congenital abnormalities of the kidney and of the urinary tract (CAKUT).
      This association increases the risk for chronic kidney disease and for evolution
      towards chronic renal failure. The congenital SK is also often associated with
      gynaecological and other abnormalities. The acquired solitary kidney can be due
      to nephrectomy on a pathological kidney which could not be conservatively treated
      or due to donation of a kidney for renal transplantation. The SK itself sometimes
      requires partial nephrectomy intervention, for example sparing surgery. Although
      the evolution is in most cases favorable, it requires attentive monitoring.

PMID- 24294811
TI  - Genetic differences between patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease.
      RA likely develops beginning with genetic risk. Investigating of preclinical
      period of RA will lead to understanding the relationships between genetic and
      environmental factors. The recent studies confirm the polygenic contribution of
      the major histocompatibility complex (MHC) to RA. Various genetic factors
      involved in the pathogenesis of RA have been discovered. HLA genes contribute
      only a portion of the genetic susceptibility to RA. There is also evidence for a
      contribution of non-class II genes to susceptibility. Non-HLA genes are also
      involved in disease pathogenesis, and identifying them remains a challenge. The
      association between RA and certain MHC alleles may be important in the
      pathogenesis of RA. In the future, research into genetic factors correlated with
      the severity of RA is expected to yield interesting and hopefully clinically
      relevant results. In this review we present the current data supporting the
      existence of susceptibility gene for RA.

PMID- 24294812
TI  - Primary eosinophilic esophagitis in children and adults: new aspects for
      diagnosis.
AB  - Eosinophilic esophagitis (EoE) is a chronic, Th2-type immune-mediated disorder.
      During the past decade, the increasing prevalence of EoE has been recognized in
      pediatric and adult populations all over the world. EoE diagnosis can be frequent
      challenging. Three criteria must be met to diagnose EoE: clinical symptoms of
      esophageal dysfunction, an esophageal biopsy with a peak eosinophil count of at
      least 15 eosinophils per high-power microscopy field and exclusion of other
      possible causes of esophageal eosinophilia. Although eosinophils mediate the EoE
      pathogenesis, proinflammatory cytokines are also critically involved. In the past
      years biologic therapeutics have revolutionized treatment of EoE.

PMID- 24294813
TI  - Evaluation of oxidative stress in patients with acute ischemic stroke.
AB  - Oxidative stress is involved in the pathogenesis of acute ischemic stroke.
      Antioxidants are consumed in the reaction with free radicals generated during the
      oxidative stress. The aim of the study was the to evaluate the oxidative stress
      in patients with acute ischemic stroke. Malondialdehyde (MDA), plasma
      glutathione, plasma glutathione peroxidase (GPX), catalase (CAT), uric acid,
      bilirubin, plasma superoxide dismutase (SOD), red blood cells superoxide
      dismutase (RBS SOD) (spectrophotometric assay), total antioxidant capacity (TAC)
      (enhanced chemiluminescence), ceruloplasmin, C-reactive protein (CRP), albumin,
      transferrin (nephelometric assay) were performed in 57 patients (mean age 73.4 +/
      6.5 years) with acute ischemic stroke within 24 hours and at 7 days after stroke
      onset as compared to 51 age-and sex-matched controls. Significantly lower values
      in the first 24 hours were: plasma glutathione, CAT, plasma SOD, RBS SOD (p <
      0.001), plasma GPX, TAC, transferrin (p < 0.05). Significantly higher values in
      the first 24 hours were: CRP (p < 0.001), MDA, uric acid (p < 0.05).
      Significantly lower values at 7 days were: TAC, albumin, transferrin (p < 0.001),
      plasma glutathione, plasma SOD, CAT (p < 0.05). Significantly higher values at 7
      days were: MDA, plasma GPX, RBC SOD, CRP, uric acid, bilirubin (p < 0.001),
      ceruloplasmin (p < 0.05). These results indicate that oxidative stress is
      increased and that the majority of antioxidants are reduced; this suggests the
      possibility of therapeutic intervention with antioxidant agents.

PMID- 24294814
TI  - The adiponectin/leptin ratio is a useful tool to evaluate the metabolic status in
      an obstetrical intensive care unit.
AB  - INTRODUCTION: Critically ill patients, including obstetrical patients, face
      undernutrition but a reliable and cost effective study to assess their
      nutritional state is still missing. Our main objective was to analyze serum
      leptin and adiponectin concentrations in puerperal women attended in an
      Obstetrical Intensive Care Unit (OICU) in order to evaluate their potential role
      as nutritional metabolic parameter. METHODS: This was a descriptive, clinical,
      longitudinal and comparative study. We evaluated the anthropometric variables,
      clinical laboratories, daily calories and adiponectin and leptin serum levels of
      16 puerperal women attended at the OICU of the Materno Perinatal Hospital "Monica
      Pretelini" (HMPMP). RESULTS: For all women there was a negative correlation with
      Spearman test between leptin the day of discharge from the obstetrical intensive
      care unit and the days of stay -0.632 (p = 0.011). Considering an
      adiponectin/leptin ratio, the media in the first day was of 0.3 (0.07-13.6) and
      in the day of discharge it was of 2.4 (0.1-24.6) in overweight women. The same
      values for obese women were of 0.3 (0.2-0.4) and 0.5 (0.3-1.2). CONCLUSION: After
      an average of six days of hospitalization, leptin showed a decrement in women
      attended at the OICU. As expected, adiponectin increased in both groups. The
      adiponectin/ leptin ratio could be a useful metabolic parameter.

PMID- 24294815
TI  - A debate on the certainty of etiology in a case of syncope.
AB  - We present the case of a 47-year-old woman with reccurent syncope. The
      investigations for establishing the etiology of syncope were extended over 4
      years and multiple possible mecahisms for the syncope were identified. Even if
      the guidelines mention a good diagnostic yield for history and initial
      evaluation, for some selected cases the initial diagnostic supposition should be
      revised.

PMID- 24294816
TI  - Complete systolic obliteration of the left ventricle due to an apical
      hypertrophic cardiomyopathy in a totally asymptomatic patient.
AB  - A 30-years-old man, subjected to an electrocardiogram for screening, showed signs
      of left ventricular hypertrophy and "giant" inverted T-waves in pre-cordial
      leads. So, a transthoracic echocardiogram and a Coronary angiography were
      performed that showed first, a normal ventricular function and second, normal
      coronary arteries. Luckily, we associated to the Coronary angiography a
      Ventriculography that revealed a marked hypertrophy particularly in the apex and
      a 90% complete tele-systolic obliteration of the left ventricle. To better
      address our diagnosis, we performed a cardiac magnetic resonance that confirmed
      the Apical Hypertrophic Cardiomyopathy (AHCM) involving concentrically the apex
      known as "spade-like configuration" and an apical akinesia with slow-flow. Since
      the patient was totally asymptomatic, he was discharged without any treatment.
      AHCM is a form of Hypertrophic Cardiomyopathy (HCM) with an hypertrophy of the
      left ventricular apex. This disease is often sporadic and among the forms of HCM
      it has a benign prognosis although in > 50% of patients AHCM is symptomatic with
      chest pain and palpitations. Our patient incredibly never had cardiac symptoms
      and was always in a good health state, so only thanks to the association of
      Ventriculography to the Coronary angiography we were able to reach this unusual
      diagnosis.

PMID- 24294817
TI  - Association between signs and symptoms of temporomandibular disorders and
      pregnancy (case control study).
AB  - Temporomandibular disorders (TMD) are a combination of multifactoral etiological
      muscular-skeletal symptoms. Prevalence is greater in women, where sexual hormones
      are important in pathogenesis, and its behavior at different stages of the
      reproductive life of women has never been fully documented. The general objective
      was to determine the association between signs and symptoms of temporomandibular
      disorders and pregnancy. A case-control study was conducted on 66 pregnant
      patients who met with a medical specialist and 66 non-pregnant women paired by
      age, who visited the General Regional Hospital 36 of Mexico's Social Security
      Institute (IMSS). These patients were examined for the Temporomandibular (TMD)
      research project to establish the prevalence of TMD in both groups. Descriptive
      variables were calculated through him SPSS 17 program and the association between
      groups with Xi Square and Ratio Possibilities (OR), The average age was 28.23 +/-
      5.9 years in both groups, with median gestation 32.97 weeks. Most of the
      participants had a domestic partner. The prevalence of TDM in the non-pregnant
      group was 45.5% and only 15.2% in the pregnant group (chi2 = 14.34, p < .000). We
      calculated the ratio of possibilities (RP) pregnant/non-pregnant with a value of
      41 with confidence intervals from 23 to 72. In conclusion, pregnancy protects
      women from TDM signs and symptoms. Pregnant women have a considerably lower
      prevalence of these disorders.

PMID- 24294818
TI  - Dental caries experience in school children and the impact of non-cavitated
      lesions on the caries index.
AB  - The purpose of this study was to evaluate the current status of dental caries in
      11 to 13 year-old schoolchildren residing in Sucre Municipality, Miranda State,
      and the impact of the non-cavitated lesion on the caries index. Twelve elementary
      schools were included in this study and a sample of 1484 children was examined
      using artificial light, a #5 mirror and a #23 probe. The criteria followed were
      those proposed by Radike (1972) as modified by Acevedo et al. (2005) in order to
      include initial non-cavitated caries lesions. Teeth were cleaned and dried for 5
      seconds with a triple syringe. Caries prevalence was 94.07% and the average DMFS
      index for the total sample was 4.35 +/- 4.21. This increased significantly to
      6.45 +/- 5.01, when the initial caries lesions were included (p < 0.05).
      According to gender, DMFS was higher in the female population (4.51 +/- 4.45)
      than in males (4.21 +/- 3.97), but the difference was not statistically different
      (p > 0.05). The same pattern was observed, when the initial caries lesions were
      added. The new mean DMFS was 6.67 +/- 5.15 and 6.26 +/- 4.88 for females and
      males, respectively. Non-cavitated lesions represent 33% of the total caries
      lesions recorded. CONCLUSION: These results show that (i) dental caries
      prevalence in this population remains high and (ii) initial lesions contribute
      significantly to the DMFS index.

PMID- 24294819
TI  - Bruxism. Masticatory implications and anxiety.
AB  - In this study we investigate the phenomenon of bruxism, defined as the act of
      clenching and/or grinding the teeth, a habit that compromises the orofacial
      region. It is often associated with emotional aspects, such as anxiety and
      stress, and may result in alterations to orofacial structures, functional
      modifications and social repercussions. The aim of this study was to determine a
      possible association between bruxism and anxiety underscoring the primary
      complaints related to masticatory function. Eighty volunteers participated in the
      study. They were divided into bruxers (N = 40) and non-bruxers (N = 40) of both
      sexes. The diagnosis of bruxism was made by clinical examination. The Trait-State
      Anxiety Inventory was used to assess anxiety levels and a questionnaire with
      structured questions related to daily activities, focusing on masticatory
      function (for the bruxism group), was applied to evaluate psychosocial aspects.
      The results of the study show a significant difference in state anxiety. Mean and
      standard deviation of state anxiety in the bruxism and non-bruxism groups was
      42.7 +/- 9.6 and 38.6 +/- 8.2 (p < or = 0.04), respectively, while trait anxiety
      had a mean and standard deviation of 44.5 +/- 11.0 and 40.7 +/- 9.5 (p < or =
      0.11). The main complaints of bruxers during mastication were facial pain and
      headache while chewing as well as the presence of clicking sounds in the jaw
      joint. Findings demonstrate an association between emotional factors such as
      anxiety and bruxism, resulting in compromised masticatory function.

PMID- 24294820
TI  - Presence and antimicrobial profile of gram-negative facultative anaerobe rods in
      patients with chronic periodontitis and gingivitis.
AB  - Chronic periodontitis is a multifactorial infectious disease associated with Gram
      negative anaerobes which are part of the subgingival microflora. In recent years,
      studies have been conducted to assess the presence of Gram-negative facultative
      anaerobes (Enterobacteriaceae) and their participation in the development and
      progression of chronic periodontitis. The aim of this study was to determine the
      presence of Enterobacteriaceae in patients with chronic periodontitis and
      gingivitis and to assess antimicrobial susceptibility of clinical isolates. A
      descriptive, observational study was performed including 64 patients with chronic
      periodontitis and 22 patients with gingivitis. Microbiological samples were taken
      from the gingival sulcus using paper points, which then were placed in
      thioglycollate broth. Samples were incubated for 4 hours at 37 degrees C and
      finally replated on MacConkey agar Bacteria were identified using the API-20E
      system (Biomerieux, France) and antimicrobial susceptibility was determined using
      the disk diffusion method. The evaluation of samples showed presence of 29
      enterobacterial species distributed as follows: 7 in the group with gingivitis
      and 22 in the group with chronic periodontitis. In the chronic periodontitis
      group the most common species were: K. oxytoca n = 5, S. liquefaciens n = 4 and
      K. pneumoniae and E. coli with n = 3. The gingivitis group had the highest
      frequency of Erwinia sp. (n = 2). Clinical isolates showed very low sensitivity
      levels to beta-lactam ampicillin and amoxicillin/ clavulanic acid, 17.2% and
      27.6% respectively, and higher sensitivity levels to ciprofloxacin (96.6%),
      amikacin (79.3%), gentamicin (68.9%) and ceftazidime, ceftriaxone, kanamycin and
      trimethoprimsulfa (65.5%). In conclusion, the existence of a high frequency of
      enterobacteria in patients with chronic periodontitis and gingivitis shows that
      periodontologists should pay greater attention to prevention protocols, and
      develop mechanical and antimicrobial therapies in which antimicrobial
      susceptibility profile reports should be considered as part of periodontal
      treatment.

PMID- 24294821
TI  - Influence of cyclical fatigue on torsional fracture morphology in endodontic
      instruments.
AB  - Cyclical fatigue may influence the appearance and propagation of the type of
      fracture of an endodontic instrument. The aim of this study was to assess the
      influence of cyclic fatigue on morphological features of torsional fracture in
      Pathfile nickel-titanium rotary instruments for surgical preparation in
      endodontics. Thirty new Pathfile instruments (Dentsply- Maillefer. Ballaigues
      Switzerland) diameter .13 and taper .02 were randomly divided into 5 groups (n =
      6). Twenty-four of them were subject to cyclical fatigue by continuous rotation
      using a stainless steel cylinder with internal bore 0.5 mm, length 25 mm, with a
      curve of 45 degrees and radius 8 mm at 5 mm from the tip, at 300 rpm and 1 Ncm
      torque for different times: A: 15 sec, B: 75 sec, C: 150 sec and D: 300 sec,
      while the fifth group was kept as a control (group N). As a second step, the
      instruments were rotated at 2 rpm and 1 Ncm torque, with their apical 3 mm fixed
      in a resin block until they suffered torsional fracture. The fracture surfaces
      were analyzed using a conventional high-vacuum scanning electron microscope
      (Phillips mod. 515) at 400x. All instruments had ductile fracture areas of
      different sizes. The ductile fracture areas were measured as percentages of the
      total area of the instrument by means of Golden Ratio (Softonic) software for
      measuring images. The data obtained were analyzed statistically using one-way
      variance analysis followed by Tukey's multiple comparison test. There were
      significant differences among groups regarding cyclic fatigue time and fragile
      fracture area (P < .001). Comparison of percentages shows five significant
      differences between N/C; N/D; A/D; C/N and C/A. No other comparison was
      significant. It is concluded that the increase in cyclical fatigue to which the
      rotating PathFile instrument is subject significantly increases the percentage of
      ductile fracture area produced by torsion.

PMID- 24294822
TI  - Effect of surface treatments on the bond strength of different resin teeth to
      complete denture base material.
AB  - Although different commercial brands of artificial teeth are available in the
      market, debonding from the denture base is still an issue when rehabilitating
      edentulous patients with conventional or implant-supported complete dentures. The
      purpose of this study was to investigate the effect of surface treatments on the
      bond strength of four artificial teeth brands to a denture base material
      polymerized by microwave energy. Forty anterior artificial teeth of each brand
      (Biolux, Trilux, Biotone IPN, and Vipi Dent Plus) were bonded to denture base
      material (VipiWave). Before processing, groups often specimens of each brand
      received surface treatment: control, monomer application (MA), air abrasion (AA)
      or diatoric cavity (DC). After processing, a blinded examiner conducted the bond
      test by applying load to the specimens (0.5 mm/min, to 45 degrees). Data were
      analyzed by one-way ANOVA followed by Tukey's test (alpha = 0.05). Biolux teeth
      have stronger bonding to denture base than Trilux (p < 0.05) in control group;
      higher bond values than Biotone IPN (p < 0.05) in MA group; and higher bond
      strength than Vipi Dent Plus and Trilux (p < 0.01) in DC group; AA had no
      differential effect for any of the brands. With regard to the effect of the
      surface treatments on bond strength within groups of commercial brand,
      statistical analysis revealed no difference among them. According to results in
      general, Biolux teeth had the strongest bonding to the denture base material
      polymerized by microwave energy. Results may assist dentists in selecting denture
      teeth from the standpoint of shear bond strength.

PMID- 24294823
TI  - Growth inhibition in rats fed inadequate and incomplete proteins: repercussion on
      mandibular biomechanics.
AB  - This study describes the effects of feeding growing rats with a diet containing
      inadequate and incomplete proteins on both the morphological and the
      biomechanical properties of the mandible. Female rats aged 30 d were fed freely
      with one of two diets, control (CD, 301 Cal/100g) and experimental (ED, 359
      Cal/100g). CD was a standard laboratory diet, while ED was a synthetic diet
      containing cornflower supplemented with vitamins and minerals. Both diets had the
      same physical characteristics. Control (C) and experimental (E) animals were
      divided into 4 groups of 10 animals each. C40 and E40 rats were fed CD and ED,
      respectively, for 40 d; C105 were fed the CD for 105 d; and E105 were fed the ED
      for 40 d and then the CD for the remainder of the experimental period (65 d).
      Mandibular growth was estimated directly on excised and cleaned bones by taking
      measurements between anatomical points. Mechanical properties of the right
      hemimandible were estimated by using a 3-point bending test to estimate the
      structural properties of the bone. Geometric properties of both the entire bone
      and the cross-section were determined. Bone material properties were calculated
      from structural and geometric properties. The left hemimandibles were ashed and
      the ash weight obtained. Rats fed the ED failed to achieve normal body weight
      gain. Complete catch-up was observed at the end of nutritional rehabilitation.
      Mandibular weight and length were negatively affected by the ED, as were the
      cross-sectional area, the mineralized cortical area, and the cross-sectional
      moment of inertia. All of these parameters showed incomplete catch-up. The
      structural bone mechanical properties indicative of strength and stiffness were
      negatively affected. Intrinsic material properties, as assessed by the modulus of
      elasticity and maximal elastic stress, were within normal values. In summary, the
      experimental bone was weaker than the control and structurally incompetent. The
      bone considered was smaller than the control bone, showing a significant
      reduction in the cross-sectional area and the moment of inertia. However,
      material properties as well as the ash fraction and degree of mineralization were
      similar in E and C bones. Therefore, the E bone was weaker than the C bone
      because of its smaller bone mass, which appears to have been negatively
      influenced by the ED in relation to its effects on overall body mass.

PMID- 24294824
TI  - Multilayered polymer-coated carbon nanotubes to deliver dasatinib.
AB  - Multilayered, multifunctional polymer coatings were grafted onto carbon nanotubes
      (CNTs) using a one-pot, ring-opening polymerization in order to control the
      release kinetic and therapeutic efficacy of dasatinib. Biocompatible,
      biodegradable multilayered coatings composed of poly(glycolide) (PGA) and
      poly(lactide) (PLA) were polymerized directly onto hydroxyl-functionalized CNT
      surfaces. Sequential addition of monomers into the reaction vessel enabled
      multilayered coatings of PLA-PGA or PGA-PLA. Poly(ethylene glycol) capped the
      polymer chain ends, resulting in a multifunctional amphiphilic coating.
      Multilayer polymer coatings on CNTs enabled control of the anticancer drug
      dasatinib's release kinetics and enhanced the in vitro therapeutic efficacy
      against U-87 glioblastoma compared to monolayer polymer coatings. 

PMID- 24294825
TI  - Lipase-catalyzed ring-opening copolymerization of epsilon-caprolactone and beta
      lactam.
AB  - The enzymatic ring-opening copolymerization of epsilon-caprolactone (epsilon-CL)
      and beta-lactam by using Candida antarctica lipase B (CAL-B) as catalyst was
      studied. Variation of the feed ratios of 25:75, 50:50, and 75:25 of epsilon
      CL/beta-lactam was performed. The products contain poly(epsilon-CL-co-beta
      lactam) and the homopolymers of poly(epsilon-CL) and poly(beta-lactam). The
      structure of the copolymers was determined by MALDI-ToF MS. Poly(epsilon-CL-co
      beta-lactam) has an alternating and random structure consisting of alternating
      repeating units with oligo(epsilon-CL) or oligo(beta-lactam). The highest
      fraction of the alternating copolymers resulted from the reaction with a feed
      ratio 50:50. The copolymer is a semicrystalline polymer with a Tm at 124  degrees
      C and Tgs at -15 and 50  degrees C. Interestingly, the copolymer also
      demonstrated cold crystallization at 29 and 74  degrees C, after quenching the
      sample from the melt in liquid nitrogen. 

PMID- 24294826
TI  - Prevalence of and risk factors for poor functioning after isolated mild traumatic
      brain injury in children.
AB  - This study aimed to determine the prevalence and predictors of poor 3 and 12
      month quality of life outcomes in a cohort of pediatric patients with isolated
      mild TBI. We conducted a prospective cohort study of children and adolescents <18
      years of age treated for an isolated mild TBI, defined as "no radiographically
      apparent intracranial injury" or "an isolated skull fracture, and no other
      clinically significant non-brain injuries." The main outcome measure was the
      change in quality of life from baseline at 3 and 12 months following injury, as
      measured by the Pediatric Quality of Life index (PedsQL). Poor functioning was
      defined as a decrease in total PedsQL score of >15 points between baseline and
      follow-up scores (at 3 and 12 months). Of the 329 patients who met inclusion
      criteria, 11.3% (95% CI 8.3-15.3%) at 3 months and 12.9% (95% CI 9.6-17.2%) at 12
      months following injury had relatively poor functioning. Significant predictors
      of poor functioning included less parental education, Hispanic ethnicity (at 3
      months following injury, but not at 12 months); low household income (at 3 and 12
      months), and Medicaid insurance (at 12 months only). Children and adolescents
      sustaining a mild TBI who are socioeconomically disadvantaged may require
      additional intervention to mitigate the effects of mild TBI on their functioning.

PMID- 24294827
TI  - "There's no chasing involved": cis/trans relationships, "tranny chasers," and the
      future of a sex-positive trans politics.
AB  - This article adds to a small, but growing, body of work on trans sexualities and
      partnerships, and provides a much-needed inquiry into the complex and contested
      politics of desire when we take trans identities, bodies, and sexualities into
      account. Using digital ethnographic data from YouTube videos along with in-person
      observational data from LGBTQ and trans conferences in the U.S., Tompkins argues
      that a sex-positive trans politics cannot emerge in trans and trans-allied
      communities if the rhetoric of the "tranny chaser" continues to inform discourses
      of desire and attraction to trans people. 

PMID- 24294828
TI  - Conserved sequence repeats of IQGAP1 mediate binding to Ezrin.
AB  - Mammalian IQGAP proteins all feature multiple ~50 amino acid sequence repeats
      near their N-termini, and little is known about the function of these "Repeats".
      We have expressed and purified the Repeats from human IQGAP1 to identify binding
      partners. We used mass spectrometry to identify 42 mouse kidney proteins that
      associate with the IQGAP1 Repeats including the ERM proteins ezrin, radixin, and
      moesin. ERM proteins have an N-terminal FERM domain (4.1, ezrin, radixin, moesin)
      through which they bind to protein targets and phosphatidylinositol 4,5
      bisphosphate (PIP2) and a C-terminal actin-binding domain and function to link
      the actin cytoskeleton to distinct locations on the cell cortex. Isothermal
      titration calorimetry (ITC) reveals that the IQGAP1 Repeats directly bind to the
      ezrin FERM domain, while no binding is seen for full-length "autoinhibited" ezrin
      or a version of full-length ezrin intended to mimic the activated protein. ITC
      also indicates that the ezrin FERM domain binds to the Repeats from IQGAP2 but
      not the Repeats from IQGAP3. We conclude that IQGAP1 and IQGAP2 are positioned at
      the cell cortex by ERM proteins. We propose that the IQGAP3 Repeats may likewise
      bind to FERM domains for signaling purposes. 

PMID- 24294829
TI  - First clinical application of octacalcium phosphate collagen composite in human
      bone defect.
AB  - We have previously demonstrated that octacalcium phosphate (OCP) collagen
      composite (OCP/collagen) promotes bone regeneration in a critical-sized bone
      defect of a rodent or canine model. This study was designed to investigate the
      bone regeneration of OCP/collagen in human bone defect as a first clinical trial.
      Two patients who had a radicular cyst or apical periodontitis consented to
      participate in our clinical study, and OCP/collagen was implanted into the
      defects after operation. Radiographic examination showed effective bone healing
      in each bone defect at 3 or 6 months. Likewise, computed tomography value
      significantly increased after implantation. Postoperative wound healing was
      uneventful, and neither infection nor allergic reaction against OCP/collagen was
      observed for the entire period. This study demonstrated that OCP/collagen would
      be safely used and enhanced bone regeneration in human bone defects. To reinforce
      the efficacy of OCP/collagen as a bone substitute material, it should be compared
      with other suitable comparators in the future. 

PMID- 24294832
TI  - The zinc transporter LIV-1 is a novel regulator of stemness in pancreatic cancer
      cells.
AB  - OBJECTIVE: Recent studies have identified the existence a portion of cancer
      cells, called "cancer stem cells", within the entire cancer tissue. Cancer stem
      cells harbor highly tumorigenic and chemo-resistant phenotypes, which lead to
      recurrence or re-growth of the tumor after surgery. The mechanisms that regulate
      the stemness of cancer cells remain largely unknown. We hypothesized that LIV-1,
      a zinc transporter, regulates the stemness in pancreatic cancer cells. MATERIAL
      AND METHODS: We established two stable Panc-1 pancreatic cancer cell lines in
      which LIV-1 expression was knocked down by the introduction of siRNA against LIV
      1. Expression of cancer stem cell-related molecules was examined by quantitative
      real-time PCR. Expression of ATP-binding cassette sub-family G member 2 was also
      determined by flow cytometry. Spheroid culture was performed in low-adhesion
      coated plates. Cell migration was determined by using a modified 2-chamber
      migration assay. In vivo tumor formation was assessed in nude mice after the
      subcutaneous injection of cancer cells. The Agilent's miRNA microarray was used
      to identify differentially expressed miRNAs. RESULTS: Knockdown of LIV-1
      expression resulted in (i) decreased expression of cancer stem cell-related
      molecules such as LIN28 and ATP-binding cassette sub-family G member 2, (ii)
      decreased spheroid-forming ability, (iii) decreased migration, (iv) decreased
      incidence of tumor formation in nude mice, and (v) upregulation of miR-7
      expression. CONCLUSIONS: Our results suggest that LIV-1 might act as a novel
      regulator of stemness in pancreatic cancer cells.

PMID- 24294831
TI  - The role of mouse strain differences in the susceptibility to fibrosis: a
      systematic review.
AB  - In humans, a number of genetic factors have been linked to the development of
      fibrosis in a variety of different organs. Seeking a wider understanding of this
      observation in man is ethically important. There is mounting evidence suggesting
      that inbred mouse strains with different genetic backgrounds demonstrate variable
      susceptibility to a fibrotic injury. We performed a systematic review of the
      literature describing strain and organ specific response to injury in order to
      determine whether genetic susceptibility plays a role in fibrogenesis. Data were
      collected from studies that were deemed eligible for analysis based on set
      inclusion criteria, and findings were assessed in relation to strain of mouse,
      type of injury and organ of investigation. A total of 44 studies were included
      covering 21 mouse strains and focusing on fibrosis in the lung, liver, kidney,
      intestine and heart. There is evidence that mouse strain differences influence
      susceptibility to fibrosis and this appears to be organ specific. For instance,
      C57BL/6J mice are resistant to hepatic, renal and cardiac fibrosis but
      susceptible to pulmonary and intestinal fibrosis. However, BALB/c mice are
      resistant to pulmonary fibrosis but susceptible to hepatic fibrosis. Few studies
      have assessed the effect of the same injury stimulus in different organ systems
      using the same strains of mouse. Such mouse strain studies may prove useful in
      elucidating the genetic as well as epigenetic factors in humans that could help
      determine why some people are more susceptible to the development of certain
      organ specific fibrosis than others. 

PMID- 24294833
TI  - Syntheses of 3,4-disubstituted pyrroles and furans via Lewis acid-promoted
      semipinacol rearrangement/alkyne-ketone metathesis reaction of (C)-2-N- or O-((3
      arylpropargyl)methyl)-tethered 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones.
AB  - The synthesis of 2,3-disubstituted pyrroles via TMSOTf-assisted cyclization
      reaction of 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones incorporating a (3
      arylpropargyltosylamino)methyl tether at the C-2 position is described. The
      reaction starts with an acid-promoted semipinacol rearrangement to give a ring
      contraction cyclopentanone moiety bearing an arylpropargylaminoacetyl side chain.
      A subsequent alkyne-ketone metathesis affords the pyrrole derivatives in good
      yields. The 3,4-disubstituted furan analogues can also be available from 3,5,5
      trimethyl-2,3-epoxycyclohexan-1-ones with a tethered arylpropargyl methyl ether
      at the C-2 position and BF3.OEt2 under an atmosphere of oxygen. 

PMID- 24294834
TI  - Combined immunodeficiency presenting with vaccine-associated paralytic
      poliomyelitis: a case report and narrative review of literature.
AB  - Neurologic abnormalities compatible with vaccine-related poliovirus infection
      (VAPP) may be a first presentation of some primary immunodeficient patients. The
      risk of VAPP rises from 1 case per 750 000 in normal population to 1 per 7000
      times higher, particularly for persons with agammaglobulinemia and
      hypogammaglobulinemia. However, there is no appropriate estimation for VAPP
      occurrence in patients with cellular immunity defects. Herein we report a case of
      combined immunodeficiency with paralytic complication due to oral polio vaccine
      and we present a literature review on this topic. 

PMID- 24294835
TI  - AgF-mediated fluorinative homocoupling of gem-difluoroalkenes.
AB  - A novel silver(I)-fluoride-mediated homocoupling reaction of beta,beta
      difluorostyrene derivatives is described. The transformation is initiated via
      nucleophilic addition of silver(I) fluoride to beta,beta-difluorostyrenes, which
      is followed by dimerization of the corresponding benzylsilver intermediates. The
      reaction shows good substrate scope, functional group tolerance, and represents
      the first report on the reactivity of (alpha-trifluoromethyl)benzylsilver
      species. 

PMID- 24294836
TI  - A method for assessing fidelity of delivery of telephone behavioral support for
      smoking cessation.
AB  - OBJECTIVES: Behavioral support for smoking cessation is delivered through
      different modalities, often guided by treatment manuals. Recently developed
      methods for assessing fidelity of delivery have shown that face-to-face
      behavioral support is often not delivered as specified in the service treatment
      manual. This study aimed to extend this method to evaluate fidelity of telephone
      delivered behavioral support. METHOD: A treatment manual and transcripts of 75
      audio-recorded behavioral support sessions were obtained from the United
      Kingdom's national Quitline service and coded into component behavior change
      techniques (BCTs) using a taxonomy of 45 smoking cessation BCTs. Interrater
      reliability was assessed using percentage agreement. Fidelity was assessed by
      comparing the number of BCTs identified in the manual with those delivered in
      telephone sessions by 4 counselors. Fidelity was assessed according to session
      type, duration, counselor, and BCT. Differences between self-reported and actual
      BCT use were examined. RESULTS: Average coding reliability was high (81%). On
      average, 41.8% of manual-specified BCTs were delivered per session (SD = 16.2),
      with fidelity varying by counselor from 32% to 49%. Fidelity was highest in pre
      quit sessions (46%) and for BCT "give options for additional support" (95%).
      Fidelity was lowest for quit-day sessions (35%) and BCT "set graded tasks" (0%).
      Session duration was positively correlated with fidelity (r = .585; p < .01).
      Significantly fewer BCTs were used than were reported as being used, t(15) = 
      5.52, p < .001. CONCLUSIONS: The content of telephone-delivered behavioral
      support can be reliably coded in terms of BCTs. This can be used to assess
      fidelity to treatment manuals and to in turn identify training needs. The
      observed low fidelity underlines the need to establish routine procedures for
      monitoring delivery of behavioral support.

PMID- 24294830
TI  - Tetrahydrobiopterin in cardiovascular health and disease.
AB  - Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme
      systems, and considerable evidence implicates BH4 as a key regulator of
      endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health
      and disease. BH4 bioavailability is determined by a balance of enzymatic de novo
      synthesis and recycling, versus degradation in the setting of oxidative stress.
      Augmenting vascular BH4 levels by pharmacological supplementation has been shown
      in experimental studies to enhance NO bioavailability. However, it has become
      more apparent that the role of BH4 in other enzymatic pathways, including other
      NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on
      important aspects of vascular homeostasis, inflammation, and cardiac function.
      This article reviews the role of BH4 in cardiovascular development and
      homeostasis, as well as in pathophysiological processes such as endothelial and
      vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We
      discuss the therapeutic potential of BH4 in cardiovascular disease states and
      attempt to address how this modulator of intracellular NO-redox balance may
      ultimately provide a powerful new treatment for many cardiovascular diseases.

PMID- 24294837
TI  - Mindfulness-based cognitive therapy for preventing relapse in recurrent
      depression: a randomized dismantling trial.
AB  - OBJECTIVE: We compared mindfulness-based cognitive therapy (MBCT) with both
      cognitive psychological education (CPE) and treatment as usual (TAU) in
      preventing relapse to major depressive disorder (MDD) in people currently in
      remission following at least 3 previous episodes. METHOD: A randomized controlled
      trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus
      TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT =
      99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance
      with its published manual, modified to address suicidal cognitions; CPE was
      modeled on MBCT, but without training in meditation. Both treatments were
      delivered through 8 weekly classes. RESULTS: Allocated treatment had no
      significant effect on risk of relapse to MDD over 12 months follow-up, hazard
      ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95%
      CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard
      ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and
      significantly interacted with allocated treatment. Among participants above
      median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs.
      CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median
      severity, there were no such differences between treatment groups. CONCLUSION:
      MBCT provided significant protection against relapse for participants with
      increased vulnerability due to history of childhood trauma, but showed no
      significant advantage in comparison to an active control treatment and usual care
      over the whole group of patients with recurrent depression.

PMID- 24294840
TI  - Induced pluripotent stem cells as cardiac arrhythmic in vitro models and the
      impact for drug discovery.
AB  - INTRODUCTION: The development of new antiarrhythmic agents is challenging and is
      hampered by high attrition rate of novel drug candidates. One of the reasons for
      this is limited predictability of existing preclinical models for drug
      assessment. Cardiomyocytes (CMs) derived from disease-specific induced
      pluripotent stem cells (iPSC) represent a novel in vitro cellular model of
      cardiac arrhythmias with an unprecedented potential for generating new
      mechanistic insight into disease pathophysiology and improving the process of
      drug development. AREAS COVERED: This review outlines recent studies
      demonstrating the suitability and limitations of iPSC-derived CMs (iPS-CMs) for
      in vitro modeling inherited arrhythmias and drug testing. The authors focus on
      channelopathies and outline the properties of iPS-CMs, highlighting their utility
      and limitations for investigating the mechanism of cardiac arrhythmias and drug
      discovery. EXPERT OPINION: The iPS-CMs represent a valuable addition to the
      already existing armamentarium of cardiac arrhythmic models. However, the
      superiority of iPS-CMs over other arrhythmia models has not yet been rigorously
      established and the limitations of the model must be overcome before its full
      potential for antiarrhythmic drug discovery can be realized. Nevertheless, iPS
      cell-based platforms hold a great potential for increasing our knowledge about
      cellular arrhythmia mechanisms and improving the drug discovery process.

PMID- 24294838
TI  - A randomized trial of assertive continuing care and contingency management for
      adolescents with substance use disorders.
AB  - OBJECTIVE: Most adolescents relapse within 90 days of discharge from residential
      substance use treatment. We hypothesized that contingency management (CM),
      assertive continuing care (ACC), and their combination (CM + ACC) would each be
      more effective than usual continuing care (UCC). METHOD: Following residential
      treatment, 337 adolescents were randomized to 4 continuing care conditions: UCC
      alone, CM, ACC, or CM + ACC. UCC was available across all conditions. Outcome
      measures over 12 months included percentage of days abstinent from alcohol, heavy
      alcohol, marijuana, and any alcohol or other drugs (AOD) using self-reports and
      toxicology testing and remission status at 12 months. RESULTS: CM had
      significantly higher rates of abstinence than UCC for heavy alcohol use, t(297) =
      2.50, p < .01, d = 0.34; any alcohol use, t(297) = 2.58, p < .01, d = 0.36; or
      any AOD use, t(297) = 2.12, p = .01, d = 0.41; and had a higher rate in
      remission, odds ratio (OR) = 2.45, 90% confidence interval (CI) [1.18, 5.08], p =
      .02. ACC had significantly higher rates of abstinence than UCC from heavy alcohol
      use, t(297) = 2.66, p < .01, d = 0.31; any alcohol use, t(297) = 2.63, p < .01, d
      = 0.30; any marijuana use, t(297) = 1.95, p = .02, d = 0.28; or any AOD use,
      t(297) = 1.88, p = .02, d = 0.30; and had higher rates in remission, OR = 2.31,
      90% CI [1.10, 4.85], p = .03. The ACC + CM condition was not significantly
      different from UCC on any outcomes. CONCLUSIONS: CM and ACC are promising
      continuing care approaches after residential treatment. Future research should
      seek to further improve their effectiveness.

PMID- 24294841
TI  - Empathy, ToM, and self-other differentiation: an fMRI study of internal states.
AB  - This study used functional magnetic resonance imaging to examine the neural
      substrates of empathy, Theory of Mind (ToM), and self-other differentiation
      involved in the adaptive understanding of people's internal states. Three
      conditions were distinguished in both sad and neutral (no obvious emotion)
      contexts. The empathy condition involved imagining what another person is feeling
      while the more cognitively loaded ToM condition involved imagining what would
      make another person feel better. The self-reference condition required
      participants to imagine how they would feel in someone else's situation. Areas
      previously implicated in empathy, ToM, and self-other differentiation were
      identified within the different conditions, regardless of emotional context.
      Specifically, the frontal and temporal poles responded more strongly for ToM than
      for empathy. The self-reference condition was associated with stronger
      dorsolateral prefrontal response than the empathy condition, while the reverse
      comparison revealed a stronger role for right frontal pole. Activations in
      frontal pole and orbitofrontal cortex were shared between the three conditions.
      Contrasts of parameter estimates demonstrated modulation by emotional context.
      The findings of common and differential patterns of responding observed in
      prefrontal and temporal regions suggest that within the social cognition network
      empathy, ToM and self-other differentiation have distinct roles that are
      responsive to context. 

PMID- 24294839
TI  - Criteria for symptom remission revisited: a study of patients affected by
      schizophrenia and schizoaffective disorders.
AB  - BACKGROUND: This study aims to compare severity criteria defined by the Remission
      in Schizophrenia Working Group (RSWGcr) with other criteria in relation to
      functional and neurocognitive outcome. METHODS: 112 chronic psychotic outpatients
      were examined. Symptomatic remission according to RSWGcr was compared with the
      outcome achieved using criteria based on PANSS Positive and Negative Scales
      (PANSS-PNScr) and the entire PANSS (PANNS-TScr). RESULTS: Remission rates were
      50%, 35% and 23% respectively at RSWGcr, PANSS-PNScr and PANNS-TScr; functional
      remission rates were 32%, 42% and 54%. Sensitivity, specificity, predictive value
      and ROC analysis demonstrated the superiority of PANSS-PNScr in identifying
      patients with higher functional and cognitive outcomes. Regression analysis
      showed a significant predictive effect of PANSS-TScr on functioning. General
      linear model analyses demonstrated significantly higher mean scores at PSP and
      BACS for patients remitted according to PANSS-TScr. CONCLUSION: The use of more
      restrictive severity criteria of remission seems to be associated with improved
      identification of truly remitted patients.

PMID- 24294842
TI  - Mutated CaV2.1 channels dysregulate CASK/P2X3 signaling in mouse trigeminal
      sensory neurons of R192Q Cacna1a knock-in mice.
AB  - BACKGROUND: ATP-gated P2X3 receptors of sensory ganglion neurons are important
      transducers of pain as they adapt their expression and function in response to
      acute and chronic nociceptive signals. The present study investigated the role of
      calcium/calmodulin-dependent serine protein kinase (CASK) in controlling P2X3
      receptor expression and function in trigeminal ganglia from Cacna1a R192Q-mutated
      knock-in (KI) mice, a genetic model for familial hemiplegic migraine type-1.
      RESULTS: KI ganglion neurons showed more abundant CASK/P2X3 receptor complex at
      membrane level, a result that likely originated from gain-of-function effects of
      R192Q-mutated CaV2.1 channels and downstream enhanced CaMKII activity. The
      selective CaV2.1 channel blocker omega-Agatoxin IVA and the CaMKII inhibitor KN
      93 were sufficient to return CASK/P2X3 co-expression to WT levels. After CASK
      silencing, P2X3 receptor expression was decreased in both WT and KI ganglia,
      supporting the role of CASK in P2X3 receptor stabilization. This process was
      functionally observed as reduced P2X3 receptor currents. CONCLUSIONS: We propose
      that, in trigeminal sensory neurons, the CASK/P2X3 complex has a dynamic nature
      depending on intracellular calcium and related signaling, that are enhanced in a
      transgenic mouse model of genetic hemiplegic migraine.

PMID- 24294843
TI  - [Clinical characteristics of 520 children with hemophilia in a single medical
      center].
AB  - OBJECTIVE: To analyze the clinical characteristics, diagnosis and treatment of
      pediatric hemophilia in single center over the decade. METHODS: A retrospective
      study was conducted with 520 hemophilic children hospitalized in our medical
      center between January 2002 and December 2012. RESULTS: All the patients were
      male including 438 hemophilia A (HA) and 82 hemophilia B (HB). There were
      significant differences in APTT between severe and mild- to moderate hemophilia
      (P<0.05). In pediatric HA and HB, delay time of diagnosis were 1.42 and 1.17
      year, respectively. Children of 7-12 years were the largest population of
      visiting a doctor, and the spontaneous bleeding episode was the main cause. The
      most common hemorrhage site was soft tissue in early childhood, but joint was
      increasingly affected with age as children growth. All bleeding sites and
      frequencies were not associated with plasma factor level of patient (P>0.05).
      Knee and anKle were mainly involved in early child, while elbow and shoulder were
      involved increasingly in later childhood. Additionally, in HA and HB, inhibitor
      occurrence were 8.9%(19/214) and 12.8%(5/39), inducing 78.9%(15/19) and
      40.0%(2/5) of high titer inhalator, and antiHCV-positive rate were 2.8%(11/397)
      and 2.5%(2/79), respectively. CONCLUSION: Our data highlights that delay in
      diagnosis and blood-borne infections were significantly reduced over the decade,
      but the development of inhibitor still remains a major challenge with wide-scale
      usage of factor in replacement therapy.

PMID- 24294844
TI  - [Detection of intron 22 inversion of factor VIII gene in severe hemophilia A
      patients].
AB  - OBJECTIVE: To investigate the incidence of intron 22 inversion (INV22) of factor
      VIII (FVIII) gene in severe hemophilia A (HA) patients, clarify its pathological
      mechanism, and identify INV22 carrier in the female family members. METHODS: One
      stage method was used to assay the FVIII activity (FVIII:C)in 126 severe HA
      patients with a median age of 14 years old (range: 4 months-63 years). INV22 was
      analyzed by long-distance polymerase chain reaction (LD-PCR) and pulsed field gel
      electrophoresis (PFGE), and pedigree were conducted in 3 involved HA families.
      RESULTS: Of all the 126 severe HA, 52 (41.3%) cases had the INV22. Four females
      including 3 mothers and 1 sister of probands were diagnosed as INV22 carriers
      among 11 suspected carrier mosaicisms from 3 INV22 positive HA families. In 8
      females from one family without HA history, the patient's mother was a INV22
      carrier, but her maternal grandmother, 2 maternal aunts, 2 female siblings and 1
      elder female cousin were negative. CONCLUSION: LD-PCR and PFGE could be used to
      diagnose severe HA patients with INV22 and identify the carriers.

PMID- 24294845
TI  - [Prophylactic G-CSF mobilized donor lymphocytes infusion after non-myeloablative
      stem cell transplantation prevents relapse in patients with high-risk leukemia].
AB  - OBJECTIVE: To evaluate the anti-leukemia effects of prophylactic G-CSF mobilized
      donor lymphocytes infusion (pG-DLI) and its relationship with the incidence of
      graft-versus-host disease (GVHD) in high-risk leukemia patients with non
      myeloablative stem cell transplantation (NST). METHODS: 12 patients with high
      risk leukemia were analyzed, including Ph+ acute lymphocytic leukemia (n=1),
      acute leukemia (AL) with persistent non-complete remission (n=2), acute myeloid
      leukemia (AML) with central nervous system (CNS) relapse (n=3), hybrid AL (n=1),
      secondary AML evolving from myelodysplastic syndrome (MDS/AML) (n=2), chronic
      myeloid leukemia in accelerated phase (CML-AP) (n=1), CML in blastic phase (CML
      BP) (n=2). All patients received non-myeloablative conditioning and pG-DLIs were
      administered 30-40 days post transplantation if no signs of GVHD were present.
      The percentage of donor cell chimera was analyzed by short tandem repeat
      polymerase chain reaction (STR-PCR) just before and after pG-DLI. The incidence
      of leukemia relapse and GVHD were observed. RESULTS: 12 high-risk leukemia
      patients with a median age of 38 (range: 29-52) years received G-DLI at a median
      interval of 35 (32-40) days. The median numbers of infused mononuclear cells
      (MNCs), CD34+, and CD3+ cells/kg recipient body weight was 2.3*108/kg,
      1.7*106/kg, and 0.6*108/kg, respectively. 10 of 12 patients had full donor
      chimera before pG-DLIs and conversion from mixed to full donor chimera occurred
      in the other 2 patients shortly after pG-DLI. Grade II acute GVHD (aGVHD) was
      observed in only 2 patients and chronic GVHD (cGVHD) developed in 6 patients,
      including involvement of skin (n=3), skin and intestine (n=2), liver (n=1). 1
      patient died of cGVHD. With a median follow-up of 40 (24-64) months, 7 patients
      are alive in remission, with 3-year actuarial overall survival (OS) and disease
      free survival (DFS) rates of the same 58.3%. CONCLUSION: Our findings indicate
      that pG-DLI after NST does not increase the risk of aGVHD, but could enhance the
      capacity graft-vs-leukemia and prevent relapse in high-risk leukemia patients.

PMID- 24294846
TI  - [Study of RON mediated invasion of Raji cell line and drug-target effects].
AB  - OBJECTIVE: To study the proto-oncogene RON mediated aggression of Raji cells and
      the inhibitory effects by monoclonal antibody Zt/f2 (2f2). METHODS: The effects
      of RON ligand macrophage stimulating protein (MSP) (2.0 nmol/L) and inhibitory
      Zt/f2 (2F2) (2.0 nmol/L) antibody on proliferation of RON positive Raji cells
      after treatment for 24 and72 hours were detected by MTT method, colony formation
      units (CFU) of Raji cells by methylcellulose semi solid culture, Raji cells
      apoptosis and cell cycle analysis by AnnexinV/PI double staining, expression of
      RON, apoptosis-related proteins, and cyclins by Western blot. RESULTS:
      (1)Compared with the cell viability (1.0) and counts of CFU (103.6+/-7.0) in
      control group, Raji cells after MSP treatment had better viability (1.35+/-0.20)
      and CFU counts (133.7+/-10.4) (P<0.05), but worse viability (0.68+/-0.11) and CFU
      counts (66.3+/-6.1) after Zt/f2 (2F2) treatment (P<0.05). (2)Percentage of Raji
      cells apoptosis after Zt/f2 (2F2) antibody treatment (12.16+/-2.33)% was
      significantly increased than the control (2.89+/-1.03)% (P<0.05). The percentage
      of Raji cells arrested in G0/G1 phase was increased after Zt/f2 (2F2) antibody
      treatment as compared to the control [ (54.96 +/-3.70)% vs (39.10+/-2.30)%,
      (P<0.05) ]. (3) High-level of RON phosphorylation and beta-catenin expression
      activated by MSP could be inhibited significantly by Zt/f2 (2F2), which also up
      regulated the expression of caspase-3, caspase-8, caspase-9 and PARP and down
      regulated anti-apoptotic MCL-1 gene and inhibitor of apoptosis protein XIAP
      expression, accompanied with G1 phase protein changes accordingly. CONCLUSION:
      MSP could aggravate Raji cells proliferation. Inversely, Zt/f2 (2F2) could
      inhibit proliferation and induce apoptosis by inhibition of RON phosphorylation
      and up-regulation of apoptosis related proteins.

PMID- 24294847
TI  - [Apoptosis and its mechanisms of spleen CD4+ CD25+ regulatory T cells in severe
      aplastic anemia mouse model].
AB  - OBJECTIVE: To explore the apoptosis and its mechanisms of spleen CD4+ CD25+
      regulatory T (Treg) cells in severe aplastic anemia (SAA) mouse model induced by
      interferon (IFN-gamma) in combination with busulphan (BU). METHODS: The BALB/c
      female mice SAA model was induced by intraperitoneal injection with IFN-gamma and
      intragastric administration with BU (combined group, n=16), with BU group (n=16),
      IFN-gamma group (n=16) and normal group (n=16) as controls. Spleen Treg cells
      were purified by using of immunomagnetic beads. Apoptosis was detected by flow
      cytometry. AKt and TGF-beta expression was measured by Western blot. RESULTS:
      Apoptosis of spleen Treg cells in combined group [(33.21+/-0.65)%] was
      significantly higher than that in BU group [(21.58+/-0.64)%], IFN-gamma group
      [(17.62+/-1.05)%], and control[(27.38+/-1.89)%] (P<0.05). A significantly lower
      expression of AKt and TGF-beta protein was also seen in combined group (0.30+/
      0.05 and 0.17+/-0.05), as compared to the other three groups (P<0.05).
      CONCLUSION: Excessive apoptosis of Treg cells was found in SAA mouse model, which
      may be a cause of Treg cells decrease in patients with AA. The down-regulated
      expression of AKt and TGF-beta could play a role in increased apoptosis of Treg
      cells. Our data may provide a new treatment strategy in AA.

PMID- 24294848
TI  - [Imbalance of Th17 and Treg cells in peripheral blood from multiple myeloma
      patients].
AB  - OBJECTIVE: To investigate the ratio of Th17 cells and CD4+CD25+Foxp3+ regulatory
      T (Treg) cells in peripheral blood from patients with multiple myeloma (MM) and
      explore its pathological effects. METHODS: 70 MM patients were divided into three
      groups: newly diagnosed group (n=30), plateau stage group (n=23) and
      relapsed/refractory group (n=17). The controls consisted of 20 healthy donors.
      The frequencies of Th17 and Treg cells were detected by flow cytometry. RESULTS:
      Compared with controls [(0.72+/-0.33)%] and plateau stage group [(0.74+/-0.29)%],
      frequencies of Th17 cells were higher in newly diagnosed group [(1.62+/-0.65)%]
      and relapsed/refractory group [(1.45+/-0.51)%], respectively (P<0.05). Compared
      with controls [(2.33+/-0.90)%] and plateau stage group [(1.69+/-0.70)%],
      frequencies of Treg cells were significantly lower in newly diagnosed group
      [(0.55+/-0.23)%] and relapsed/refractory group [(0.82+/-0.54)%], respectively
      (P<0.05). The ratios of Th17/Treg in newly diagnosed group and
      relapsed/refractory group were higher than those in controls (P<0.05). There were
      no differences of the frequencies of CD3+CD4+ T cells and Th17 cells between
      plateau stage group and controls. The frequencies of Treg cells were
      significantly lower in plateau stage group than that in controls (P<0.05), and
      the ratio of Th17/Treg was significantly higher in plateau stage group than that
      in controls (P<0.05). CONCLUSION: The remarkable abnormality of T cells subsets
      was reduction of CD4+ T cells in MM. Higher frequency of Th17 and lower ratio of
      Treg could lead to imbalance of Th17/Treg, which may play a critical role in the
      pathogenesis of MM.

PMID- 24294849
TI  - [Effects of down-regulated TRAF6 gene expression on the proliferation and
      apoptosis in multiple myeloma cells].
AB  - OBJECTIVE: To investigate the down-regulated TRAF6 gene expression and its
      effects on proliferation and apoptosis in multiple myeloma (MM) cells. METHODS:
      Detection of TRAF6 expression were conducted by RT-PCR and Western blot in MM
      cell lines of KM3, U266, RPMI8226 and primary cells from patients. RPMI8226 cell
      lines were transfected with siRNA of TRAF6. The efficiency of transfection was
      identified by using of fluorescence microscope, RT-PCR, and Western blot. The
      levels of proliferation were analyzed by CCK-8 method under the different
      concentrations of siRNA. Apoptosis rate were detected with Hoechst33258/PI double
      staining by flow cytometry. Apoptosis related proteins Bcl-2, BAX, and NF-kappaB
      signal pathway were observed before and after siRNA transfection by Western blot.
      RESULTS: The levels of TRAF6 mRNA and protein in MM cell lines, especially in
      primary myeloma cells, were significantly higher than those in controls. After
      transfected with 50 nmol/L siRNA in RPMI8226 cells, the relative level of TRAF6
      mRNA (0.49+/-0.24) was significantly lower than that in non-transfected group
      (1.87+/-0.23) and idling group (1.74+/-0.35). The proliferation rate of siRNA
      transfected cells decreased with dose dependence (P<0.01). The apoptosis rates
      increased from 11.20% (before transfection) to 51.82% (after transfection),
      accompanied by down-regulated Bcl-2 protein, NF-kappaB signal pathway (p-p65 and
      p52), and up-regulated BAX protein. CONCLUSION: TRAF6 expression was high in
      myeloma cells. TRAF6 siRNA could inhibit proliferation of myeloma cells and
      induce apoptosis mediated by NF-kappaB classical and alternative pathway in
      myeloma cells.

PMID- 24294850
TI  - [Sensitivity to bortezomib of RPIM8226 cells after co-cultured with down
      regulated Cav-1 expression HUVECs].
AB  - OBJECTIVE: To investigate the sensitivity to bortezomib of RPMI8226 cells after
      co-cultured with down-regulated Caveolin (Cav)-1 expression of HUVECs by
      transfection with Cav-1 shRNA (HUVECs(Cav-1 low)). METHODS: Exposure to
      bortezomib with or without 50 nmol/L dexamethasone at different concentration,
      the proliferation of RPMI8226 was analyzed by MTT assay when it was cultured
      alone or co-cultured with HUVECs(Cav-1 low). Cav-1 expression was detected by
      using of Western blot and cell cycle, apoptosis and the level of reactive oxygen
      species (ROS) were analyzed by flow cytometry. RESULTS: Cav-1 expression was
      notably down-regulated in HUVECs(Cav-1 low) (0.2199+/-0.0288 vs 1.3195+/-0.2393)
      (P<0.01). The IC(50) of bortezomib for RPMI8226 cultured alone, co-cultured with
      HUVECs orHUVECCav- 1 low were 20 nmol/L, 50 nmol/L and 65 nmol/L, respectively.
      The percentages of G0/G1 phase in RPMI8226 cultured alone, co-cultured with
      HUVECs and HUVECs(Cav-1 low) were 28.49%, 30.41%, and 36.15% respectively. The
      protection of RPMI 8226 against apoptosis by HUVECs was demonstrated that the
      apoptosis/death rates were 66.8%, 10.7% and 8.6% in RPMI8226 cultured alone, co
      cultured with HUVECs and HUVECs(Cav-1 low) after exposure to 20 nmol/L bortezomib
      for 24 h. RPMI8226 could induce the oxidative stress of HUVECs before and after
      co-culture. The ROS level was raised from 15.0% to 35.2% in RPMI8226, from 80.4%
      to 91.0% in HUVECs, and from 84.6% to 96.8% in HUVECs(Cav-1 low). CONCLUSION: The
      down-regulated Cav-1 expression of HUVECs could promote proliferation and induce
      apoptosis of RMPI8226 cells, lead to G0/G1 phase arrest, and reduce the
      sensitivity to bortezomib.

PMID- 24294851
TI  - [Enhanced cytotoxicity against leukemia cells of natural Killer cells from cord
      blood after expansion in vitro].
AB  - OBJECTIVE: To investigate the enhanced cytotoxicity against leukemia cells of
      natural Killer (NK) cells from cord blood (CB) after expansion in vitro. METHODS:
      NK cells was expanded on a layer of trophoblast cells with irradiated K562-mb15
      41BBL cell line for 21 days. The levels of receptors on NK cells were detected by
      flow cytometry. Cytotoxicity of expanded NK cells against leukemia cells and
      specific ligand of immunoglobulin like(Ig- liKe)receptors were assessed using
      51Cr released assay. RESULTS: There were no differences of inhibitory receptors
      expression between fresh NK cells and expanded NK cells [CD158a:(16.77+/-11.65)%
      vs(14.37+/-11.12)%, P>0.05; CD158b: (42.48+/-18.11)% vs (40.92+/-19.02)%, P>0.05;
      NKG2A: (70.20+/-18.43)% vs (78.90+/-13.69)%, P>0.05], but higher activated
      receptors expression on expanded NK cells [NKp30: (54.10+/-13.27)% vs (4.14+/
      2.05)%, P<0.05; NKp44: (72.10+/-17.30)% vs (0.52+/-1.16)%, P<0.05; NKp46:
      (80.63+/-14.01)% vs (44.19+/-6.19)%, P<0.05; NKG2D: (97.50+/-2.55)% vs (72.25+/
      14.35)%, P<0.05]. Expanded NK cells showed higher cytotoxicity against leuKemia
      cell lines than fresh NK cells [K562: (74.3+/-3.6)% vs (55.3+/-4.2)%, P<0.05;
      Raji: (60.6+/-5.0)% vs (12.0+/-3.6)%, P<0.05]. CD158a- CD158b- NK cells had
      higher cytotoxicity on four types of target cells, but CD158a+CD158b- CB-NK cell
      had lower cytotoxicity on 221-Cw4 and 221-Cw3Cw4 cells. CD158a- CD158b+ CB- NK
      cells had lower cytotoxicity on 221-Cw3 and 221-Cw3Cw4, but CD158a+CD158b+ CB-NK
      cells had higher cytotoxicity on 721- 221 cells. CONCLUSION: Expression of
      activated receptors of expanded NK cells were up-regulated, but no changes of
      inhibitory receptors. Expanded NK cells showed high cytotoxicity against leukemia
      cells and kept the specificity of ligand of Ig-like receptors, which could be
      beneficial to cell-therapy for tumor.

PMID- 24294852
TI  - [Clinical analysis of non-Hodgkin lymphoma after renal transplantation].
AB  - OBJECTIVE: To investigate the clinical characteristics and therapeutic outcomes
      of non-Hodgkin lymphoma (NHL) occurring after renal transplantation. METHODS: We
      reviewed a total population of 2045 adult kidney recipients between January 1998
      and October 2012, 12 of which developed NHL. Their clinical features and outcomes
      were analyzed. RESULTS: 12 patients with a median age of 52.5 (range: 30-68)
      years old, including 5 males and 7 females, were diagnosed as diffuse large B
      cell lymphoma (DLBCL) at a median interval of 84 (range: 12-253) months after
      transplantation. The incidences of developing NHL at 2-year, 5-year and 10-year
      were 0.10%, 0.15% and 0.44%, respectively. The locations of lymphoma were
      diverse, including central nervous system, stomach, liver, kidney, pancreas,
      uterus, ribs, sKin, soft palate and Waldeyer ring. After reduction of
      immunosuppression intensity, 3 cases received surgical therapy, 6 cases with
      chemotherapy, 1 case with surgery combined with chemotherapy, 1 case with
      chemotherapy combined with irradiation and 1 case without treatment. The overall
      response rate was 81.8%, including 8 cases with CR, 1 with PR and 2 with
      progression. During a median of 11.5 (range: 1 to 130) months follow-up, 3
      patients died. CONCLUSION: NHL was a rare but serious complication after renal
      transplantation occurred with bimodal distribution, which was symptomatic
      diversity and non- specificity. The most histopathological type was DLBCL.
      Reduction of immunosuppression intensity was not enough to get efficacy, and CHOP
      with or without rituximab was effective in the treatment of NHL after renal
      transplantation.

PMID- 24294853
TI  - [Detection and analysis of factor VIII exon 14 mutation in severe hemophilia A
      patients].

PMID- 24294854
TI  - [Adult acute lymphoblastic leukemia with atypical BCR-ABL transcript e1a3: a case
      report and literature review].

PMID- 24294855
TI  - [Expression of T-bet mRNA and GATA-3 mRNA in peripheral blood mononuclear cells
      of patients with diffuse large B cell lymphoma].

PMID- 24294856
TI  - [Norcantharidin induce anti-myeloma effect on nude mouse xenografts through NF
      kappaB signal pathway].

PMID- 24294857
TI  - [Application of fluorescence in situ hybridization on archived bone marrow smears
      in retrospective diagnosis of hematologic malignancies].

PMID- 24294858
TI  - [Agnogenic eosinophilia in hematologic malignancies: four cases report and
      literature review].

PMID- 24294859
TI  - [Regulation of hematopoietic stem cell in endothelial niche].

PMID- 24294860
TI  - [Mechanisms of osteogenic inhibition in myeloma bone disease and its targeted
      therapy].

PMID- 24294861
TI  - [Consensus on the management of lymphoma with HBV infection].

PMID- 24294862
TI  - [Expert consensus on adult acute lymphoblastic leukemia in China-interpretation
      of diagnosis and prognosis stratification].

PMID- 24294863
TI  - [Expert consensus on adult acute lymphoblastic leukemia in China--thoughts and
      interpretation of Ph+ acute lymphoblastic leukemia].

PMID- 24294864
TI  - Does emotion help or hinder reasoning? The moderating role of relevance.
AB  - Some prior research has shown that emotion impairs logicality in deductive
      reasoning tasks, while other research suggests improved performance with
      emotional contents. We suggest that relevance, whether the affective state is
      associated with the semantic contents of the reasoning task, may be crucial in
      explaining these apparently inconsistent findings. This hypothesis is based on a
      framework distinguishing between integral emotions, where affective responses are
      evoked by the semantic contents of the target task, and incidental emotions,
      where affective responses are not related to the task. In 4 experiments we
      examined the effect of emotion on conditional reasoning when affective responses
      were relevant and irrelevant. We used images presented simultaneously with the
      reasoning stimuli (Experiments 1, 2, and 3) or videos presented prior to the
      reasoning stimuli (Experiment 4) that were either emotional or neutral and
      semantically related or not to the conditional statements. Results showed that
      emotion decreased the proportion of normatively correct responses only in the
      irrelevant condition. In the relevant condition, emotion did not produce reliable
      deleterious effects. We used reaction time and skin conductance measures to
      investigate the physiological and cognitive correlates of these effects. Results
      are discussed in terms of the distinction between incidental and integral
      emotions.

PMID- 24294865
TI  - The politics of the face-in-the-crowd.
AB  - Recent work indicates that the more conservative one is, the faster one is to
      fixate on negative stimuli, whereas the less conservative one is, the faster one
      is to fixate on positive stimuli. The present series of experiments used the face
      in-the-crowd paradigm to examine whether variability in the efficiency with which
      positive and negative stimuli are detected underlies such speed differences.
      Participants searched for a discrepant facial expression (happy or angry) amid a
      varying number of neutral distractors (Experiments 1 and 4). A combination of
      response time and eye movement analyses indicated that variability in search
      efficiency explained speed differences for happy expressions, whereas variability
      in post-selectional processes explained speed differences for angry expressions.
      These results appear to be emotionally mediated as search performance did not
      vary with political temperament when displays were inverted (Experiment 2) or
      when controlled processing was required for successful task performance
      (Experiment 3). Taken together, the present results suggest political temperament
      is at least partially instantiated by attentional biases for emotional material.

PMID- 24294866
TI  - Attentional flexibility during approach and avoidance motivational states: the
      role of context in shifts of attentional breadth.
AB  - In the present studies, we aimed to understand how approach and avoidance states
      affect attentional flexibility by examining attentional shifts on a trial-by
      trial basis. We also examined how a novel construct in this area, task context,
      might interact with motivation to influence attentional flexibility. Participants
      completed a modified composite letter task in which the ratio of global to local
      targets was varied by block, making different levels of attentional focus
      beneficial to performance on different blocks. Study 1 demonstrated that, in the
      absence of a motivation manipulation, switch costs were lowest on blocks with an
      even ratio of global and local trials and were higher on blocks with an uneven
      ratio. Other participants completed the task while viewing pictures (Studies 2
      and 3) and assuming arm positions (Studies 2 and 4) to induce approach,
      avoidance, and neutral motivational states. Avoidance motivation reduced switch
      costs in evenly proportioned contexts, whereas approach motivation reduced switch
      costs in mostly global contexts. Additionally, approach motivation imparted a
      similar switch cost magnitude across different contexts, whereas avoidance and
      neutral states led to variable switch costs depending on the context. Subsequent
      analyses revealed that these effects were driven largely by faster switching to
      local targets on mostly global blocks in the approach condition. These findings
      suggest that avoidance facilitates attentional shifts when switches are frequent,
      whereas approach facilitates responding to rare or unexpected local stimuli. The
      main implication of these results is that motivation has different effects on
      attentional shifts depending on the context.

PMID- 24294867
TI  - Narrative centrality and negative affectivity: independent and interactive
      contributors to stress reactions.
AB  - Reactions to stressful negative events have long been studied using approaches
      based on either the narrative interpretation of the event or the traits of the
      individual. Here, we integrate these 2 approaches by using individual-differences
      measures of both the narrative interpretation of the stressful event as central
      to one's life and the personality characteristic of negative affectivity. We show
      that they each have independent contributions to stress reactions and that high
      levels on both produce greater than additive effects. The effects on
      posttraumatic stress symptoms are substantial for both undergraduates (Study 1, n
      = 2,296; Study 3, n = 488) and veterans (Study 2, n = 104), with mean levels for
      participants low on both measures near floor on posttraumatic stress symptoms and
      those high on both measures scoring at or above diagnostic thresholds. Study 3
      included 3 measures of narrative centrality and 3 of negative affectivity to
      demonstrate that the effects were not limited to a single measure. In Study 4 (n
      = 987), measures associated with symptoms of posttraumatic stress correlated
      substantially with either measures of narrative centrality or measures of
      negative affectivity. The concepts of narrative centrality and negative
      affectivity and the results are consistent with findings from clinical
      populations using similar measures and with current approaches to therapy. In
      broad nonclinical populations, such as those used here, the results suggest that
      we might be able to substantially increase our ability to account for the
      severity of stress response by including both concepts.

PMID- 24294868
TI  - Awareness of implicit attitudes.
AB  - Research on implicit attitudes has raised questions about how well people know
      their own attitudes. Most research on this question has focused on the
      correspondence between measures of implicit attitudes and measures of explicit
      attitudes, with low correspondence interpreted as showing that people have little
      awareness of their implicit attitudes. We took a different approach and directly
      asked participants to predict their results on upcoming Implicit Association Test
      (IAT) measures of implicit attitudes toward 5 social groups. We found that
      participants were surprisingly accurate in their predictions. Across 4 studies,
      predictions were accurate regardless of whether implicit attitudes were described
      as true attitudes or culturally learned associations (Studies 1 and 2),
      regardless of whether predictions were made as specific response patterns (Study
      1) or as conceptual responses (Studies 2-4), and regardless of how much
      experience or explanation participants received before making their predictions
      (Study 4). Study 3 further suggested that participants' predictions reflected
      unique insight into their own implicit responses, beyond intuitions about how
      people in general might respond. Prediction accuracy occurred despite generally
      low correspondence between implicit and explicit measures of attitudes, as found
      in prior research. Altogether, the research findings cast doubt on the belief
      that attitudes or evaluations measured by the IAT necessarily reflect unconscious
      attitudes.

PMID- 24294870
TI  - Dissociating preview validity and preview difficulty in parafoveal processing of
      word n + 1 during reading.
AB  - Many studies have shown that previewing the next word n + 1 during reading leads
      to substantial processing benefit (e.g., shorter word viewing times) when this
      word is eventually fixated. However, evidence of such preprocessing in fixations
      on the preceding word n when in fact the information about the preview is
      acquired is far less consistent. A recent study suggested that such effects may
      be delayed into fixations on the next word n + 1 (Risse & Kliegl, 2012). To
      investigate the time course of parafoveal information-acquisition on the control
      of eye movements during reading, we conducted 2 gaze-contingent display-change
      experiments and orthogonally manipulated the processing difficulty (i.e., word
      frequency) of an n + 1 preview word and its validity relative to the target word.
      Preview difficulty did not affect fixation durations on the pretarget word n but
      on the target word n + 1. In fact, the delayed preview-difficulty effect was
      almost of the same size as the preview benefit associated with the n + 1 preview
      validity. Based on additional results from quantile-regression analyses on the
      time course of the 2 preview effects, we discuss consequences as to the
      integration of foveal and parafoveal information and potential implications for
      computational models of eye guidance in reading.

PMID- 24294871
TI  - Nonverbal communicative signals modulate attention to object properties.
AB  - We investigated whether the social context in which an object is experienced
      influences the encoding of its various properties. We hypothesized that when an
      object is observed in a communicative context, its intrinsic features (such as
      its shape) would be preferentially encoded at the expense of its extrinsic
      properties (such as its location). In 3 experiments, participants were presented
      with brief movies, in which an actor either performed a noncommunicative action
      toward 1 of 5 different meaningless objects, or communicatively pointed at 1 of
      them. A subsequent static image, in which either the location or the identity of
      an object changed, tested participants' attention to these 2 kinds of
      information. Throughout the 3 experiments we found that communicative cues tended
      to facilitate identity change detection and to impede location change detection,
      whereas in the noncommunicative contexts we did not find such a bidirectional
      effect of cueing. The results also revealed that the effect of the communicative
      context was a result the presence of ostensive-communicative signals before the
      object-directed action, and not to the pointing gesture per se. We propose that
      such an attentional bias forms an inherent part of human communication, and
      function to facilitate social learning by communication.

PMID- 24294872
TI  - Perceptual animacy: visual search for chasing objects among distractors.
AB  - Anthropomorphic interactions such as chasing are an important cue to perceptual
      animacy. A recent study showed that the detection of interacting (e.g., chasing)
      stimuli follows the regularities of a serial visual search. In the present set of
      experiments, we explore several variants of the chasing detection paradigm in
      order to investigate how human observers recognize chasing objects among
      distractors although there are no distinctive visual features attached to
      individual objects. Our results indicate that even a spatially separated
      presentation of potentially chasing pairs of objects requires attention at least
      for object selection (Experiment 1). In the chasing detection framework, a chase
      among nonchases is easier to find than a nonchase among chases, suggesting that
      cues indicating the presence of a chase prevail during chasing detection
      (Experiment 2). Spatial proximity is one of these cues toward the presence of a
      chase because decreasing the distance between chasing objects leads to shorter
      detection latencies (Experiment 3). Finally, our results indicate that single
      objects provide the basis of chasing detection rather than pairs of objects.
      Participants would rather search for one object that is approaching any other
      object in the display than for a pair of objects involved in a chase (Experiments
      4 and 5). Taken together, these results suggest that participants recognize a
      chase by detecting one object that is approaching any of the other objects in the
      display.

PMID- 24294873
TI  - End-state comfort trumps handedness in object manipulation.
AB  - A goal of research on human perception and performance is to explore the relative
      importance of constraints shaping action selection. The present study concerned
      the relative importance of two constraints that have not been directly
      contrasted: (1) the tendency to grasp objects in ways that afford comfortable or
      easy-to-control final postures; and (2) the tendency to grasp objects with the
      dominant rather than the nondominant hand. We asked participants to reach out and
      grasp a horizontal rod whose left or right end was to be placed into a target
      after a 90 degrees  rotation. In one condition, we told participants which hand
      to use and let them choose an overhand or underhand initial grasp. In another
      condition, we told participants which grasp to use and let them choose either
      hand. Participants sacrificed hand preference to perform the task in a way that
      ensured a comfortable or easy to control thumb-up posture at the time of object
      placement, indicating that comfort trumped handedness. A second experiment
      confirmed that comfort was indeed higher for thumb-down postures than thumb-up
      postures. A third experiment confirmed that the choice data could be linked to
      objective performance differences. The results point to the importance of
      identifying constraint weightings for action selection and support an account of
      hand selection that ascribes hand preference to sensitivity to performance
      differences. The results do not support the hypothesis that hand preference
      simply reflects a bias to use the dominant hand.

PMID- 24294874
TI  - The impact of alertness on cognitive control.
AB  - Many previous studies have found that an increase in phasic or tonic alertness
      impairs cognitive control, even though overall response times are decreased. This
      counterintuitive pattern of behavior is still poorly understood. Using a
      computational model, we show that the behavioral pattern follows directly from
      two simple and well-supported assumptions: increased alertness reduces the time
      needed for stimulus encoding; and cognitive control takes time to develop. The
      simulation results suggest that, although the arousal system and cognitive
      control system may be anatomically distinct, their effects on information
      processing may interact to produce a seemingly complicated pattern of behavior.

PMID- 24294875
TI  - Teachers' perceptions of students' mathematics proficiency may exacerbate early
      gender gaps in achievement.
AB  - A recent wave of research suggests that teachers overrate the performance of
      girls relative to boys and hold more positive attitudes toward girls' mathematics
      abilities. However, these prior estimates of teachers' supposed female bias are
      potentially misleading because these estimates (and teachers themselves) confound
      achievement with teachers' perceptions of behavior and effort. Using data from
      the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K),
      Study 1 demonstrates that teachers actually rate boys' mathematics proficiency
      higher than that of girls when conditioning on both teachers' ratings of behavior
      and approaches to learning as well as past and current test scores. In other
      words, on average girls are only perceived to be as mathematically competent as
      similarly achieving boys when the girls are also seen as working harder, behaving
      better, and being more eager to learn. Study 2 uses mediation analysis with an
      instrumental-variables approach, as well as a matching strategy, to explore the
      extent to which this conditional underrating of girls may explain the widening
      gender gap in mathematics in early elementary school. We find robust evidence
      suggesting that underrating girls' mathematics proficiency accounts for a
      substantial portion of the development of the mathematics achievement gap between
      similarly performing and behaving boys and girls in the early grades.

PMID- 24294876
TI  - The company they keep and avoid: social goal orientation as a predictor of
      children's ethnic segregation.
AB  - This study examined whether social goal orientation (i.e., demonstration
      approach, demonstration-avoid, and social development goals) predicts changes in
      ethnic segregation among 4th and 5th grade African American and European American
      children (n = 713, ages 9-11 years) from fall to spring. Segregation measures
      were (a) same-ethnicity favoritism in friendships, (b) same-ethnicity favoritism
      in peer group affiliations, and (c) cross-ethnicity dislike. Social goal
      orientation was asymmetrically associated with ethnic segregation for the 2
      groups. Among African Americans, aspiring to achieve high social status predicted
      increases in same-ethnicity favoritism and cross-ethnicity dislike. Among
      European Americans, aspiring to achieve high social status predicted decreases in
      same-ethnicity favoritism.

PMID- 24294877
TI  - Development of preference for conspecific faces in human infants.
AB  - Previous studies have proposed that humans may be born with mechanisms that
      attend to conspecifics. However, as previous studies have relied on stimuli
      featuring human adults, it remains unclear whether infants attend only to adult
      humans or to the entire human species. We found that 1-month-old infants (n = 23)
      were able to differentiate between human and monkey infants' faces; however, they
      exhibited no preference for human infants' faces over monkey infants' faces (n =
      24) and discriminated individual differences only within the category of human
      infants' faces (n = 30). We successfully replicated previous findings that 1
      month-old infants (n = 42) preferred adult humans, even adults of other races, to
      adult monkeys. Further, by 3 months of age, infants (n = 55) preferred human
      faces to monkey faces with both infant and adult stimuli. Human infants'
      spontaneous preference for conspecific faces appears to be initially limited to
      conspecific adults and afterward extended to conspecific infants. Future research
      should attempt to determine whether preference for human adults results from some
      innate tendency to attend to conspecific adults or from the impact of early
      experiences with adults.

PMID- 24294878
TI  - Orthographic and phonological contributions to reading development: tracking
      developmental trajectories using masked priming.
AB  - The present study used a variant of masked priming to track the development of 2
      marker effects of orthographic and phonological processing from Grade 1 through
      Grade 5 in a cross-sectional study. Pseudohomophone (PsH) priming served as a
      marker for phonological processing, whereas transposed-letter (TL) priming was a
      marker for coarse-grained orthographic processing. The results revealed a clear
      developmental picture. First, the PsH priming effect was significant and remained
      stable across development, suggesting that phonology not only plays an important
      role in early reading development but continues to exert a robust influence
      throughout reading development. This finding challenges the view that more
      advanced readers should rely less on phonological information than younger
      readers. Second, the TL priming effect increased monotonically with grade level
      and reading age, which suggests greater reliance on coarse-grained orthographic
      coding as children become better readers. Thus, TL priming effects seem to be a
      good marker effect for children's ability to use coarse-grained orthographic
      coding to speed up direct lexical access in alphabetic languages. The results
      were predicted by the dual-route model of orthographic processing, which suggests
      that direct orthographic access is achieved through coarse-grained orthographic
      coding that tolerates some degree of flexibility in letter order.

PMID- 24294879
TI  - Developmental trajectories of African American adolescents' family conflict:
      differences in mental health problems in young adulthood.
AB  - Family conflict is a salient risk factor for African American adolescents' mental
      health problems. No study we are aware of has estimated trajectories of their
      family conflict and whether groups differ in internalizing and externalizing
      problems during the transition to young adulthood, a critical antecedent in adult
      mental health and psychopathology. As hypothesized, latent class growth analysis
      approximated 4 developmental trajectories of family conflict during high school
      for 681 African American adolescents (49% boys). Trajectory classes differed in
      anxiety, depressive symptoms, and violent behavior at age 20, supporting
      expectations that adolescents demonstrating elevated levels and atypical
      trajectories of family conflict in high school would report greater mental health
      problems as young adults. Family conflict jeopardizes African American
      adolescents' transition to young adulthood by contributing to mental health
      problems.

PMID- 24294881
TI  - The role of moral emotions in the development of children's sharing behavior.
AB  - This study investigated the role of moral emotions in the development of
      children's sharing behavior (N = 244 4-, 8-, and 12-year-old children).
      Children's sympathy was measured with both self- and primary caregiver-reports,
      and participants anticipated their negatively and positively valenced moral
      emotions (i.e., feeling guilty, sad, or bad; and feeling proud, happy, or good)
      following actions that either violated or upheld moral norms. Sharing was
      measured through children's allocation of resources in the dictator game.
      Children's self-reported sympathy emerged as a significant predictor of sharing
      in early childhood. For children with low levels of sympathy, sharing was also
      predicted by negatively valenced moral emotions following the failure to perform
      prosocial actions. In addition, results demonstrated an age-related increase in
      sharing for boys between ages 4 and 8 and a decrease in sharing for boys between
      ages 8 and 12. We discuss the findings in relation to the emergence of 2
      compensatory emotional pathways to sharing, 1 via sympathy and 1 via negatively
      valenced moral emotions.

PMID- 24294880
TI  - Academic achievement as a moderator of genetic influences on alcohol use in
      adolescence.
AB  - Prior research suggests a link between academic performance and alcohol use
      during adolescence, but the degree to which this association reflects actual
      protective effects continues to be debated. We investigated the role of genetic
      factors in the association between academic achievement and adolescent alcohol
      use and whether achievement might constrain the translation of genetic influences
      on drinking into actual behavior (a Gene * Environment interaction). Analysis of
      twin data from Add Health (n = 399 monozygotic and dizygotic twin pairs) revealed
      not only common genetic factors underlying the association between achievement
      and alcohol consumption but also evidence for a gene-environment interaction.
      Specifically, the protective effect of achievement operated by moderating
      heritability of alcohol use, which was particularly salient for adolescents at
      high genetic risk for alcohol use.

PMID- 24294882
TI  - Developmental trajectories of work values and job entitlement beliefs in the
      transition to adulthood.
AB  - Employing a life span developmental systems perspective, this study used a 5-wave
      (1985-1992) Canadian longitudinal data set (N = 404) to examine trajectories of
      intrinsic and extrinsic work values and job entitlement beliefs from age 18 to
      25. Piecewise growth models (Slope 1: age 18-20; Slope 2: age 20-25) showed
      intriguing patterns of change. Unconditional and conditional models suggested
      downward trends in all 3 measures from age 18 to 20. After age 20, the 2 work
      values reversed direction. Competing scarcity and value reinforcement hypotheses
      guided the analysis of change in work values and job entitlement beliefs
      conditional on unemployment experiences and postsecondary education pathways.
      Supporting a scarcity hypothesis, more unemployment from age 18 to 20 was
      associated with a faster increase in intrinsic and extrinsic work values, and a
      slower decrease in job entitlement beliefs from age 20 to 25. In line with a
      value reinforcement hypothesis, more unemployment from age 20 to 25 was
      associated with a slower concurrent increase in intrinsic work values. A
      postsecondary selection effect was observed; individuals who eventually obtained
      a university degree had higher intrinsic work values and job entitlement beliefs
      at age 18. Also congruent with a scarcity hypothesis, young adults with only a
      high school education experienced a significantly faster increase in extrinsic
      work values from age 20 to 25. This study highlights the transition to adulthood
      as a key developmental period for change in work values and beliefs.

PMID- 24294883
TI  - Developmental change in proactive interference across the life span: evidence
      from two working memory tasks.
AB  - Working memory (WM) as the ability to temporarily maintain and manipulate various
      kinds of information is known to be affected by proactive interference (PI) from
      previously relevant contents, but studies on developmental changes in the
      susceptibility to PI are scarce. In the present study, we investigated life span
      development of item-specific PI. To this end, 92 individuals between the ages of
      8 and 74 years completed a recent-probes task and an n-back task that both
      composed experimental manipulations of PI. Regarding global WM development, young
      adults had higher WM performance than children and older adults in both tasks.
      Significant PI * Age interactions revealed that susceptibility to PI changed over
      the life span in both tasks, whereas the developmental course of PI differed
      between the tasks: Children committed more PI-related errors than young adults in
      the recent-probes task but showed marginally less PI in the n-back task.
      Regarding reaction time costs, children did not differ from adults in the recent
      probes task and were less affected than adults in the n-back. Older adults showed
      more PI-related errors than young adults in both tasks. Therefore, as expected,
      item-specific PI changed over the life span with the young adults being less
      susceptible to PI than children and older adults. The diverging developmental
      effects of PI across both tasks, especially in the children, are supposed to
      reflect different causes for the difficulties regarding resisting PI in children
      and older adults. These might concern differently developed underlying cognitive
      processes such as inhibition or recollection, or different responses to task
      demands across both tasks.

PMID- 24294884
TI  - Establishing and explaining the testing effect in free recall for young children.
AB  - Research has consistently shown memory is enhanced when learning combines test
      trials with study trials compared with study trials alone (i.e., testing effect).
      However, the majority of work on testing effects has involved undergraduate
      students. In the current experiment, the authors examined testing effects in 2
      groups of elementary school children. First and 3rd graders learned 1 list of
      words in a test-plus-restudy condition and a 2nd list of words in a restudy
      condition. In addition to examining the benefits of testing in children, the
      authors examined possible explanations for the memorial benefits of testing that
      have received initial support in adult populations (Zaromb & Roediger, 2010).
      Results showed that the benefits of testing extend to elementary school children
      and that testing enhanced item-specific processing but not relational processing.
      Third graders were also aware of the memorial benefits of testing, whereas 1st
      graders were not. Most important, even 1st graders benefit from testing, in part
      because testing allows them to capitalize on their ability to process item
      specific information.

PMID- 24294885
TI  - On the affective force of "nasty love".
AB  - Tackling the mimetic logic of sex-gender that limits the transsexual subject's
      sexuality into seeming a poor representation, the author argues that trans
      pornography and autoethnographic accounts from trans scholars emphasize the
      affective dimension of trans sex, a material remainder absent from mimetic
      theories of sexuality. Developing concepts from Alfred North Whitehead's process
      philosophy, in tandem with Morty Diamond's film Trans Entities: The Nasty Love of
      Papi and Wil (2007) and a selection of trans theorists, this article elaborates
      on the horizon of affective potential opened by transgender, brown, kinky, and
      pornographic "nastiness." The event of "nasty love" solicits a differential
      becoming, growing the edge of self.

PMID- 24294886
TI  - Patient-specific 3D microfluidic tissue model for multiple myeloma.
AB  - In vitro culturing of primary multiple myeloma cells (MMC) has been a major
      challenge as this plasma cell malignancy depends on the bone marrow environment
      for its survival. Using a microfluidic platform to emulate the dynamic physiology
      of the bone marrow microenvironment, we report here a new approach for culturing
      difficult to preserve primary human MMC. The system uses a three-dimensional
      ossified tissue to mimic the tumor niche and recapitulate interactions between
      bone marrow cells and osteoblasts (OSB). To this end, the human fetal OSB cell
      line hFOB 1.19 was cultured in an eight-chamber microfluidic culture device to
      facilitate the seeding of mononuclear cells from bone marrow aspirates from three
      multiple myeloma patients. Optical microscopy, used for real-time monitoring of
      mononuclear cell interactions with the ossified tissue, confirmed that these are
      drawn toward the OSB layer. After 3 weeks, cocultures were characterized by flow
      cytometry to evaluate the amount of expansion of primary MMC (with CD138(+) and
      CD38(+)CD56(+) phenotypes) in this system. For each of the three patients
      analyzed, bone marrow mononuclear cells underwent, on an average, 2 to 5
      expansions; CD38(+)CD56(+) cells underwent 1 to 3 expansions and CD138(+) cells
      underwent 2.5 to 4.6 expansions. This approach is expected to provide a new
      avenue that can facilitate: (1) testing of personalized therapeutics for multiple
      myeloma patients; (2) evaluation of new drugs without the need for costly animal
      models; and (3) studying the biology of multiple myeloma, and in particular, the
      mechanisms responsible for drug resistance and relapse. 

PMID- 24294887
TI  - Pharmacokinetics and treatment efficacy of camptothecin nanocrystals on lung
      metastasis.
AB  - Cancer metastasis is difficult to treat, and its outcome becomes dreadful for a
      patient. Lung is a major metastatic site for many types of cancers, and the need
      for finding effective treatment for lung metastasis cannot be overemphasized. In
      a previous study, we showed that camptothecin nanocrystals demonstrated greater
      anticancer efficacy and achieved significantly higher concentration in lungs than
      a conventional, solution-based formulation. In this study, we further determined
      the pharmacokinetics of camptothecin nanocrystals in rats and investigated
      treatment efficacy in mice against metastatic lung tumors. The results show that
      camptothecin nanocrystals were capable of eliciting greater antimetastatic
      efficacy and achieve a longer survival time in the murine model compared with
      camptothecin salt solution. The study suggests that using engineered, solid
      nanoparticles may be a feasible approach in the treatment of lung cancer and lung
      metastatic cancer. 

PMID- 24294889
TI  - Using deuterium in drug discovery: leaving the label in the drug.
AB  - Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its
      utility in mechanistic, spectroscopic, and tracer studies. In fact, well-known
      applications utilizing deuterium exist within every subdiscipline in
      pharmaceutical discovery and development. Recent emphasis on incorporation of
      deuterium into the active pharmaceutical ingredient has come about as a result of
      inquiries into the potential for substantial benefits of the deuterium kinetic
      isotope effect on the safety and disposition of the drug substance. This
      Perspective traces the author's experience in reviving and expanding this
      potential utility, first suggested many decades prior by the discoverer of this,
      the simplest of all isotopes. 

PMID- 24294890
TI  - Novel approaches to the development of tyrosine kinase inhibitors and their role
      in the fight against cancer.
AB  - INTRODUCTION: Protein tyrosine kinase inhibitors are currently one of the most
      important classes of cancer drugs and one of the most impressive approaches of
      targeted cancer therapy. Aberrant activation of tyrosine kinase pathways is among
      the most dysregulated molecular pathways in human cancers; therefore, a large
      number of tyrosine kinases may serve as valuable molecular targets. To date,
      several inhibitors of tyrosine kinases have been approved and there are hundreds
      more compounds that are in various stages of development. Because of the
      deregulation in human malignancies, the ABL1, SRC, the epidermal growth factor
      receptor and the vascular endothelial growth factor receptor kinases are among
      the protein kinases that are considered as prime molecular targets for selective
      inhibition. AREAS COVERED: This review focuses on most important small-molecule
      inhibitors that serve as a model for future development. They also provide a
      broad overview of some of the new approaches and challenges in the field. EXPERT
      OPINION: With the exception of a few malignancies seemingly driven by a limited
      number of genetic lesions, current targeted therapeutic approaches have shown
      only limited efficacy in advanced cancers. Consequently, more sophisticated
      strategies, such as identification of pathogenic 'driver' mutations and
      optimization of personalized therapies are needed.

PMID- 24294888
TI  - Valproic acid protects motor neuron death by inhibiting oxidative stress and
      endoplasmic reticulum stress-mediated cytochrome C release after spinal cord
      injury.
AB  - Both oxidative stress and endoplasmic reticulum (ER) stress are known to
      contribute to secondary injury, ultimately leading to cell death after spinal
      cord injury (SCI). Here, we showed that valproic acid (VPA) reduced cell death of
      motor neurons by inhibiting cytochrome c release mediated by oxidative stress and
      ER stress after SCI. After SCI, rats were immediately injected with VPA (300
      mg/kg) subcutaneously and further injected every 12 h for an indicated time
      period. Motor neuron cell death at an early time after SCI was significantly
      attenuated by VPA treatment. Superoxide anion (O2-) production and inducible NO
      synthase (iNOS) expression linked to oxidative stress was increased after injury,
      which was inhibited by VPA. In addition, VPA inhibited c-Jun N-terminal kinase
      (JNK) activation, which was activated and peaked at an early time after SCI.
      Furthermore, JNK activation and c-Jun phosphorylation were inhibited by a broad
      spectrum reactive oxygen species (ROS) scavenger, Mn (III) tetrakis (4-benzoic
      acid) porphyrin (MnTBAP), indicating that ROS including O2- increased after SCI
      probably contribute to JNK activation. VPA also inhibited cytochrome c release
      and caspase-9 activation, which was significantly inhibited by SP600125, a JNK
      inhibitor. The levels of phosphorylated Bim and Mcl-1, which are known as
      downstream targets of JNK, were significantly reduced by SP600125. On the other
      hand, VPA treatment inhibited ER stress-induced caspase-12 activation, which is
      activated in motor neurons after SCI. In addition, VPA increased the Bcl-2/Bax
      ratio and inhibited CHOP expression. Taken together, our results suggest that
      cell death of motor neurons after SCI is mediated through oxidative stress and ER
      stress-mediated cytochrome c release and VPA-inhibited cytochrome c release by
      attenuating ROS-induced JNK activation followed by Mcl-1 and Bim phosphorylation
      and ER stress-coupled CHOP expression.

PMID- 24294891
TI  - Quality education: the clinical application.

PMID- 24294892
TI  - Reflections on the starfish and the spider.
AB  - Organizations have varied configurations-top down, bottom up, matrixed, or
      flattened. This column explores the organizational structures described as
      resembling either a starfish or a spider in relation to the Professional Nurse
      Educators Group (PNEG), continuing education providers, and, most especially, the
      annual PNEG conference. The characteristics of effective catalysts within
      decentralized organizations are included.

PMID- 24294893
TI  - A nursing education strategic plan for conquering catheter-associated urinary
      tract infections.
AB  - Catheter-associated urinary tract infections (CAUTIs) intercept opportunities for
      hospitals to achieve quality patient care outcomes, maintain sound financial
      performance, and ensure a positive health care experience. Nurse educators play a
      key role in designing effective strategies and establishing important
      partnerships aimed at reducing CAUTIs in hospitalized patients.

PMID- 24294894
TI  - The language of scholarship for novice writers.
AB  - This article is an introduction to the language that is required to convey
      nursing knowledge through essays, dissertations, and articles in peer-reviewed
      journals. The tentative style of scholarly language is explored. Key elements of
      the uniform structure of headings, citations, and references are considered.
      Guidelines for reviewing one's own paper using computer-processing strategies are
      shared.

PMID- 24294896
TI  - Graph representation of high-dimensional alpha-helical membrane protein data.
AB  - BACKGROUND: In genomics and proteomics, membrane protein analysis have shown that
      such analyses are very important to support the understanding of complex
      biological processes. In Genome-wide investigations of membrane proteins a large
      number of short, distinct sequence motifs has been revealed. Such motifs found so
      far support the understanding of the folded membrane protein in the membrane
      environment. They provide important information about functional or stabilizing
      properties. Recently several integrative approaches have been proposed to extract
      meaningful information out of the membrane environment. However, many information
      based approaches deliver results having deficits of visualisation outputs.
      Outgoing from high-throughput protein data analysis, these outputs play an
      important role in the evaluation of high-dimensional protein data, to establish a
      biological relationship and ultimately to provide useful information for
      research. RESULTS: We have evaluated different resulting graphs generated from
      statistical analysis of consecutive motifs in helical structures of the membrane
      environment. Our results show that representative motifs with high occurrence in
      all investigated protein families are responsible for the general importance in
      alpha-helical membrane structure formation. Further, motifs which often occur
      with others in their function as so called "hubs" lead to the assumption, that
      these motifs constitute as important components in helical structures within the
      membrane. Otherwise, consecutive motifs and hubs which show a high occurrence in
      certain families only can be classified as important for family-specific
      functional characteristics. Summarized, we are able to bridge our graphical
      results from high-throughput analysis of membrane proteins over networking with
      databases to a biological context. CONCLUSIONS: Our results and the corresponding
      graphical visualisation support the understanding and interpretation of structure
      forming and functional motifs of membrane proteins. Our results are useful to
      interpret and refine results of common developed approaches. At last we show a
      simple way to visualise high-dimensional protein data in context to biological
      relevant information.

PMID- 24294898
TI  - Effects of temperature and salinity on emergence of Gynaecotyla adunca cercariae
      from the intertidal gastropod Ilyanassa obsoleta.
AB  - Fluctuating abiotic conditions within intertidal zones have been shown to affect
      the emergence of free-swimming trematode infectious stages (cercariae) from their
      gastropod first intermediate hosts, likely reflecting adaptations to maximize
      transmission in this marine environment. We investigated the influences of
      temperature (17 and 22 C) and salinity (25, 30, and 35 ppt) on the emergence of
      marine cercariae (Gynaecotyla adunca) from their mud snail first intermediate
      host ( Ilyanassa obsoleta ). Cercariae emerged in greater numbers at 22 C and the
      2 lowest salinities, with a sharp decrease at the 35 ppt level, but there was no
      interactive effect. We discuss these patterns of G. adunca emergence as possible
      adaptations to facilitate transmission to its amphipod second intermediate host (
      Corophium volutator ) in conditions common to the Upper Bay of Fundy.

PMID- 24294897
TI  - Adaptation to bipolar disorder and perceived risk to children: a survey of
      parents with bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BPD) is a common condition associated with
      significant morbidity and reduced quality of life. In addition to challenges
      caused by their mood symptoms, parents affected with BPD harbor concerns about
      the mental health of their children. Among adult parents who perceive themselves
      to have BPD, this study aims to examine participants' coping methods; identify
      predictors of adaptation; assess parental perceptions of risks for mood disorders
      among their children; and describe the relationships among illness appraisals,
      coping, adaptation to one's own illness, and perceived risk to one's children.
      METHODS: Parents who self-identified as having BPD completed a web-based survey
      that assessed dispositional optimism, coping, perceived illness severity,
      perceived etiology of BPD, perceived risk to offspring, and adaptation to BPD.
      Participants had at least one unaffected child who was 30 years of age or below.
      RESULTS: 266 parents were included in the analysis. 87% of parents endorsed a
      "somewhat greater" or "much greater" risk for mood disorders in one's child(ren)
      than someone without a family history. Endorsing a genetic/familial etiology to
      BPD was positively correlated with perceived risk for mood disorders in children
      (rs = .3, p < 0.01) and active coping with BDP (r = .2, p < 0.01). Increased
      active coping (beta = 0.4, p < 0.001) and dispositional optimism (beta = 0.3, p <
      0.001) were positively associated with better adaptation, while using denial
      coping was negatively associated with adaptation (beta = -0.3, p < 0.001). The
      variables explained 55.2% of the variance in adaptation (F = 73.2, p < 0.001).
      Coping mediated the effect of perceived illness severity on adaptation.
      CONCLUSIONS: These data inform studies of interventions that extend beyond
      symptom management and aim to improve the psychological wellbeing of parents with
      BPD. Interventions targeted at illness perceptions and those aimed at enhancing
      coping should be studied for positive effects on adaptation. Parents with BPD may
      benefit from genetic counseling to promote active coping with their condition,
      and manage worry about perceived risk to their children.

PMID- 24294899
TI  - Defined DNA-mediated assemblies of gene-expressing giant unilamellar vesicles.
AB  - The technological aspects of artificial vesicles as prominent cell mimics are
      evolving toward higher-order assemblies of functional vesicles with tissuelike
      architectures. Here, we demonstrate the spatially controlled DNA-directed bottom
      up synthesis of complex microassemblies and macroassemblies of giant unilamellar
      vesicles functionalized with a basic cellular machinery to express green
      fluorescent protein and specified neighbor-to-neighbor interactions. We show both
      that the local and programmable DNA pairing rules on the nanoscale are able to
      direct the microscale vesicles into macroscale soft matter assemblies and that
      the highly sensitive gene-expression machinery remains intact and active during
      multiple experimental steps. An in silico model recapitulates the experiments
      performed in vitro and covers additional experimental setups highlighting the
      parameters that control the DNA-directed bottom-up synthesis of higher-order self
      assembled structures. The controlled assembly of a functional vesicle matrix may
      be useful not only as simplified natural tissue mimics but also as artificial
      scaffolds that could interact and support living cells. 

PMID- 24294900
TI  - A new analytical bench assay for the determination of arylsulfatase a activity
      toward galactosyl-3-sulfate ceramide: implication for metachromatic
      leukodystrophy diagnosis.
AB  - Here, we present the design and validation of a new assay for the diagnosis of
      metachromatic leukodystrophy. The method is highly specific, simple,
      reproducible, and straightforward. In our spectrophotometric method, the
      determination of arylsulfatase A (ARSA) activity toward the natural substrate,
      galactosyl-3-sulfate ceramide (or sulfatide), is performed using neat sulfatide
      without chemical modification. This confers to the assay high analytical
      specificity. The hydrolyzed sulfatide is monitored upon inclusion of the
      colorimetric reagent Azure A. The nonhydrolyzed sulfatide-Azure A is recovered
      and measured at a wavelength of lambda = 650 nm. Thus, ARSA activity toward the
      sulfatide is obtained by subtracting the nonhydrolyzed sulfatide from the total
      sulfatide used in the enzyme reaction (sulfatide-Azure A present in a parallel
      assay performed in the absence of ARSA). Within a clinical context, our method
      definitely discriminated between healthy subject samples and metachromatic
      leukodystrophy patient samples, and, therefore, it is suitable for diagnostic
      applications and for monitoring the efficacy of therapeutic treatments in
      patients or animal models. 

PMID- 24294901
TI  - Ginsenoside Rh2-B1 stimulates cell proliferation and IFN-gamma production by
      activating the p38 MAPK and ERK-dependent signaling pathways in CTLL-2 cells.
AB  - CONTEXT: Ginsenoside Rh2, an active component of ginseng, exhibits
      immunoregulatory and anti-inflammatory properties. Rh2-B1, a sulfated derivative,
      was prepared to enhance its water solubility. We studied the effect of Rh2-B1 on
      CTLL-2, a CD8+ cytotoxic T cell line that was known for protecting against viral
      infection. OBJECTIVE: We aimed to investigate the effect of Rh2-B1 on interferon
      (IFN)-gamma production and cell proliferation and its possible mechanism.
      MATERIALS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) was employed to
      analyze the IFN-gamma concentration of the whole blood and the supernatant of
      CTLL-2 cell culture. Cell proliferation assay was conducted using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Western blots
      were used to evaluate changes in signal transduction pathways in CTLL-2 cells.
      RESULTS: Rh2-B1 was able to enhance IFN-gamma production from whole blood culture
      of Balb/c mice. We then evaluated the effect of Rh2-B1 on a cytotoxic T cell
      line, CTLL-2 for cell proliferation, IFN-gamma production and its molecular
      mechanism. Rh2-B1 promoted cell proliferation and IFN-gamma production of CTLL-2
      cells. It also induced activation of p38 mitogen-activated protein kinase (MAPK)
      and extracellular-signal-regulated kinases (ERK), but inhibited p56 Lck and
      transducer and activator of transcription 5 (STAT5) expression. The effect was
      blocked by the specific p38 MAPK inhibitor SB203580 and ERK inhibitor U0126.
      CONCLUSION: Rh2-B1 could stimulate cell proliferation and IFN-gamma production by
      activating the p38 MAPK- and ERK-dependent signaling pathways in cytotoxic T
      cells. This may be a novel medicine for treatment of viral infections.

PMID- 24294902
TI  - Phenotypic and functional maturation of murine dendritic cells induced by 18
      alpha- and beta-glycyrrhetinic acid.
AB  - Various studies have described glycyrrhizin (GL), an active triterpenoic saponin
      extract of licorice roots, as an anti-inflammatory, antiviral, antimicrobial,
      anti-tumor and immunomodulating agent. The activity of GL has been mainly
      attributed to its metabolites, 18-alpha (GA) and 18-beta-glycyrrhetinic acid
      (GB), which their mechanism of action on the immune system cells is not clearly
      known. In this study, we have investigated the effects of GA and GB on the immune
      system by targeting dendritic cells and analyzing phenotypic and functional
      maturity of murine dendritic cells (DCs) after treatment with these components.
      Stimulation of DCs with GA and GB resulted in up-regulation of CD40, CD86 and MHC
      II molecules indicating their effects on the maturation of DCs. These components
      induced the allogenic immunostimulatory capacity of DCs by stimulating the
      proliferation of T cells and production of the T helper (h)1-promoting cytokine,
      IL-12. They also increased the production of IFN-gamma by T cells in mixed
      lymphocyte reaction. In conclusion, these results indicate that GA and GB may
      insert their immunomodulatory effects by enhancing DC maturation and modulating
      Th1/Th2 response through an increase in Th1 responses, implying their beneficial
      in host defense against infectious diseases.

PMID- 24294903
TI  - A new class of antitumor compounds: 5'-nor and 5',6'-seco derivatives of
      vinblastine-type alkaloids.

PMID- 24294905
TI  - Asymmetric Diels-Alder reaction of 3-olefinic benzofuran-2-ones and polyenals:
      construction of chiral spirocyclic benzofuran-2-ones.
AB  - A highly enantioselective Diels-Alder reaction of 3-olefinic benzofuran-2-ones
      with polyenals catalyzed by diphenylprolinolsilyl ether through a trienamine
      activation strategy was developed. 

PMID- 24294904
TI  - Binding to WGR domain by salidroside activates PARP1 and protects hematopoietic
      stem cells from oxidative stress.
AB  - AIMS: A component of the base excision repair pathway, poly(ADP-ribose)
      polymerase-1 (PARP1) functions in multiple cellular processes, including DNA
      repair and programmed cell death. We previously showed that Salidroside, a
      phenylpropanoid glycoside isolated from medicinal plants, prevented the loss of
      hematopoietic stem cells (HSCs) in native mice and rescued HSCs repopulating in
      transplanted recipients under oxidative stress. The aim of this study was to
      investigate the mechanism by which PARP1 activation by Salidroside maintains HSCs
      under oxidative stress. RESULTS: We found that although there were no spontaneous
      defects in hematopoiesis in Parp1(-/-) mice, oxidative stress compromised the
      repopulating capacity of Parp1(-/-) HSCs in transplanted recipient mice. A
      biochemical study using truncated proteins lacking the defined functional domains
      of PARP1 showed that the tryptophan-glycine-arginine-rich (WGR) domain of PARP1
      was critical for Salidroside binding and subsequent PARP1 activation under
      oxidative stress. Functionally, complementation of Parp1(-/-) HSCs with full
      length PARP1WT, but not the PARP1R591K mutant in WGR domain restored Salidroside
      stimulated PARP1 activation in vitro. Mechanistically, activated PARP1 by
      Salidroside enhanced the repopulating capacity of the stressed HSCs by
      accelerating oxidative DNA damage repair. INNOVATIONS AND CONCLUSION: Our
      findings reveal the action of mechanism for Salidroside in PARP1 stimulation and
      a novel role of PARP1 activation in maintaining HSC function under oxidative
      stress.

PMID- 24294906
TI  - Establishing cooperation in a mixed-motive social dilemma. An fMRI study
      investigating the role of social value orientation and dispositional trust.
AB  - When people are confronted with social dilemmas, their decision-making strategies
      tend to be associated with individual social preferences; prosocials have an
      intrinsic willingness to cooperate, while proselfs need extrinsic motivators
      signaling personal gain. In this study, the biological roots for the
      proselfs/prosocials concept are explored by investigating the neural correlates
      of cooperative versus defect decisions when participants engage in a series of
      one-shot, anonymous prisoner's dilemma situations. Our data are in line with
      previous studies showing that prosocials activate several social cognition
      regions of the brain more than proselfs (here: medial prefrontal cortex, temporo
      parietal junction, and precuneus BA 7 (Brodmann area 7), and that dispositional
      trust positively affects prosocials' decisions to cooperate. At the neural level,
      however, dispositional trust appears to exert a greater marginal effect on brain
      activity of proselfs in three social cognition regions, which does not translate
      into an increase in cooperation. An event-related analysis shows that cooperating
      prosocials show significantly more activation in the precuneus (BA 7) than
      proselfs. Based on previous research, we interpret this result to be consistent
      with prosocials' enhanced tendency to infer the intentions of others in social
      dilemma games, and the importance of establishing norm congruence when they
      decide to cooperate. 

PMID- 24294907
TI  - Risk factors for lethal outcome in patients with delirium tremens -
      psychiatrist's perspective: a nested case-control study.
AB  - BACKGROUND: The aim was to identify potential risk factors for lethal outcome in
      patients with delirium tremens (DT) treated in the psychiatric setting. METHODS:
      In a nested case-control study, a total of 190 medical records of patients with
      DT hospitalized at the Psychiatric Clinic in Serbia between 2002 and 2011 were
      reviewed and analyzed. The characteristics of patients who died (cases) were
      compared with those who survived (controls). For each case, two controls (matched
      for age, gender, and year of hospitalization) were randomly chosen. RESULTS:
      Significant differences between cases and controls were found for serum potassium
      levels (p < 0.001), the number of hospitalizations (p < 0.001), and duration of
      hospitalization (p < 0.001). A significant association with lethal outcome was
      found for serum potassium levels even in the normal range (adjusted odds ratio
      40.52; 95% CI 1.20, >1,000.00; p = 0.004). CONCLUSIONS: Even though the number
      and duration of psychiatric hospitalizations were identified as factors
      determining survival after admission for DT, only serum potassium levels were
      found to be significant. Patients with an increase in potassium (or absence of
      hypokalemia) may require more intensive treatment. Monitoring of serum levels of
      potassium is important not only as an indicator for replacement but also as an
      indicator of maladaptation.

PMID- 24294908
TI  - Efficient large-scale generation of functional hepatocytes from mouse embryonic
      stem cells grown in a rotating bioreactor with exogenous growth factors and
      hormones.
AB  - INTRODUCTION: Embryonic stem (ES) cells are considered a potentially advantageous
      source of hepatocytes for both transplantation and the development of
      bioartificial livers. However, the efficient large-scale generation of functional
      hepatocytes from ES cells remains a major challenge, especially for those methods
      compatible with clinical applications. METHODS: In this study, we investigated
      whether a large number of functional hepatocytes can be differentiated from mouse
      ES (mES) cells using a simulated microgravity bioreactor. mES cells were cultured
      in a rotating bioreactor in the presence of exogenous growth factors and hormones
      to form embryoid bodies (EBs), which then differentiated into hepatocytes.
      RESULTS: During the rotating culture, most of the EB-derived cells gradually
      showed the histologic characteristics of normal hepatocytes. More specifically,
      the expression of hepatic genes and proteins was detected at a higher level in
      the differentiated cells from the bioreactor culture than in cells from a static
      culture. On further growing, the EBs on tissue-culture plates, most of the EB
      derived cells were found to display the morphologic features of hepatocytes, as
      well as albumin synthesis. In addition, the EB-derived cells grown in the
      rotating bioreactor exhibited higher levels of liver-specific functions, such as
      glycogen storage, cytochrome P450 activity, low-density lipoprotein, and
      indocyanine green uptake, than did differentiated cells grown in static culture.
      When the EB-derived cells from day-14 EBs and the cells' culture supernatant were
      injected into nude mice, the transplanted cells were engrafted into the recipient
      livers. CONCLUSIONS: Large quantities of high-quality hepatocytes can be
      generated from mES cells in a rotating bioreactor via EB formation. This system
      may be useful in the large-scale generation of hepatocytes for both cell
      transplantation and the development of bioartificial livers.

PMID- 24294911
TI  - Development of 3D dynamic flow model of human liver and its application to
      prediction of metabolic clearance of 7-ethoxycoumarin.
AB  - Primary and cryopreserved hepatocytes and immortalized hepatic cell lines in
      static two-dimensional monolayer culture format have been widely used as in vitro
      liver models for studies of xenobiotic metabolism, enzyme induction, hepatocyte
      regeneration, and hepatotoxicity. However, the tissue structure and metabolic
      capacity in these liver models are often ill-defined and are not well preserved
      compared to in vivo liver-specific architecture and functions. For this reason,
      we developed a three-dimensional (3D) dynamic flow model with primary human
      hepatocytes, which was optimized for cell seeding density, medium composition,
      and extracellular matrix proteins. Human hepatocytes cultured in this system were
      maintained for up to 7 weeks and reproducibly recapitulated in vivo liver-like
      structure and important liver-specific functions, such as albumin/total protein
      production, glucose utilization, lactate production, and cytochrome P450 (CYP)
      3A4 activity across multiple tissue donors. The in vitro intrinsic clearance
      (CLint) of 7-ethoxycoumarin (7-EC) was determined from human hepatocytes cultured
      in the 3D dynamic flow model and compared to that in hepatocyte suspension. The 7
      EC CLint values varied among individual batches and/or the two different in vitro
      liver models used in this study. The 3D flow model appeared to give more
      reproducible and stable estimates of clearance that is similar to previously
      published values. Overall, the results from these studies demonstrate that this
      culture system could be a valuable tool for making more accurate predictions of
      the metabolic clearance and long-term effects of chemicals and their metabolites
      in a complex 3D environment under dynamic flow. 

PMID- 24294910
TI  - Delivery of chemically glycosylated cytochrome c immobilized in mesoporous silica
      nanoparticles induces apoptosis in HeLa cancer cells.
AB  - Cytochrome c (Cyt c) is a small mitochondrial heme protein involved in the
      intrinsic apoptotic pathway. Once Cyt c is released into the cytosol, the caspase
      mediated apoptosis cascade is activated resulting in programmed cell death.
      Herein, we explore the covalent immobilization of Cyt c into mesoporous silica
      nanoparticles (MSN) to generate a smart delivery system for intracellular drug
      delivery to cancer cells aiming at affording subsequent cell death. Cyt c was
      modified with sulfosuccinimidyl-6-[3'-(2-pyridyldithio)-propionamido] hexanoate
      (SPDP) and incorporated into SH-functionalized MSN by thiol-disulfide
      interchange. Unfortunately, the delivery of Cyt c from the MSN was not efficient
      in inducing apoptosis in human cervical cancer HeLa cells. We tested whether
      chemical Cyt c glycosylation could be useful in overcoming the efficacy problems
      by potentially improving Cyt c thermodynamic stability and reducing proteolytic
      degradation. Cyt c lysine residues were modified with lactose at a lactose-to
      protein molar ratio of 3.7 +/- 0.9 using mono(lactosylamido)-mono(succinimidyl)
      suberate linker chemistry. Circular dichroism (CD) spectra demonstrated that part
      of the activity loss of Cyt c was due to conformational changes upon its
      modification with the SPDP linker. These conformational changes were prevented in
      the glycoconjugate. In agreement with the unfolding of Cyt c by the linker, a
      proteolytic assay demonstrated that the Cyt c-SPDP conjugate was more susceptible
      to proteolysis than Cyt c. Attachment of the four lactose molecules reversed this
      increased susceptibility and protected Cyt c from proteolytic degradation.
      Furthermore, a cell-free caspase-3 assay revealed 47% and 87% of relative caspase
      activation by Cyt c-SPDP and the Cyt c-lactose bioconjugate, respectively, when
      compared to Cyt c. This again demonstrates the efficiency of the glycosylation to
      improve maintaining Cyt c structure and thus function. To test for cytotoxicity,
      HeLa cells were incubated with Cyt c loaded MSN at different Cyt c concentrations
      (12.5, 25.0, and 37.5 MUg/mL) for 24-72 h and cellular metabolic activity
      determined by a cell proliferation assay. While MSN-SPDP-Cyt c did not induced
      cell death, the Cyt c-lactose bioconjugate induced significant cell death after
      72 h, reducing HeLa cell viability to 67% and 45% at the 25 MUg/mL and 37.5
      MUg/mL concentrations, respectively. Confocal microscopy confirmed that the MSN
      immobilized Cyt c-lactose bioconjugate was internalized by HeLa cells and that
      the bioconjugate was capable of endosomal escape. The results clearly demonstrate
      that chemical glycosylation stabilized Cyt c upon formulation of a smart drug
      delivery system and upon delivery into cancer cells and highlight the general
      potential of chemical protein glycosylation to improve the stability of protein
      drugs. 

PMID- 24294912
TI  - Revealing strong nanocomposite hydrogels reinforced by cellulose nanocrystals:
      insight into morphologies and interactions.
AB  - Understanding the reinforcement mechanism by dispersing nanoscale particles into
      a polymer matrix is a critical challenge toward refining control of the composite
      properties. In this paper, the morphologies and interactions of cellulose
      nanocrystal/poly(acrylic acid) (CNC/PAA) nanocomposite hydrogels are demystified
      based on a facile synthetic platform. Two sources of CNCs with different aspect
      ratios are applied to model the reinforcement process, and the uniaxial tensile
      measurements indicate that the CNC aspect ratio and the nanocomposite mechanical
      behaviors are coupled, where the values of aspect ratios and nonpermanent
      interactions between the fillers and matrix dominate the reinforcement. Dynamic
      mechanical analysis is performed to examine the nature of the constrained polymer
      as the semicrystalline fractions, and the results indicate that polymer chain
      mobility in the vicinity of CNC surfaces is significantly reduced, providing new
      insight into the origin of the reinforcement mechanism. Rheological analysis and
      transmission electron microscopy observations show that both stepwise
      dissociation and polymer chain rearrangements contribute to the viscoelastic
      behaviors of the nanocomposite hydrogels. The increased modulus of the hydrogels
      is correlated to the volume of the constrained polymer, where the CNCs impart
      significant enhancement to the entanglement network. This study of the structure
      property relationship deepens the understanding of the filler reinforcement
      mechanism and provides valuable knowledge for designing high performance
      nanocomposite hydrogels from cellulose as a raw material. 

PMID- 24294909
TI  - Novel multi-system functional gains via task specific training in spinal cord
      injured male rats.
AB  - Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative
      therapy used to enhance locomotor recovery. There is evidence, primarily
      anecdotal, also associating LT with improvements in bladder function and
      reduction in some types of SCI-related pain. In the present study, we determined
      if a step training paradigm could improve outcome measures of locomotion, bladder
      function, and pain/allodynia. After a T10 contusive SCI trained animals (adult
      male Wistar rats), trained animals began quadrupedal step training beginning 2
      weeks post-SCI for 1 h/day. End of study experiments (3 months of training)
      revealed significant changes in limb kinematics, gait, and hindlimb flexor
      extensor bursting patterns relative to non-trained controls. Importantly,
      micturition function, evaluated with terminal transvesical cystometry, was
      significantly improved in the step trained group (increased voiding efficiency,
      intercontraction interval, and contraction amplitude). Because both SCI and LT
      affect neurotrophin signaling, and neurotrophins are involved with post-SCI
      plasticity in micturition pathways, we measured bladder neurotrophin mRNA.
      Training regulated the expression of nerve growth factor (NGF) but not BDNF or
      NT3. Bladder NGF mRNA levels were inversely related to bladder function in the
      trained group. Monitoring of overground locomotion and neuropathic pain
      throughout the study revealed significant improvements, beginning after 3 weeks
      of training, which in both cases remained consistent for the study duration.
      These novel findings, improving non-locomotor in addition to locomotor functions,
      demonstrate that step training post-SCI could contribute to multiple quality of
      life gains, targeting patient-centered high priority deficits.

PMID- 24294913
TI  - MicroRNA let-7a and let-7f as novel regulatory factors of the sika deer (Cervus
      nippon) IGF-1R gene.
AB  - MicroRNAs and their roles in rapid antler growth and regeneration have attracted
      much attention. In the present study, we examined the effects of microRNAs let-7a
      and let-7f on antler cell proliferation. We used a luciferase reporter screen to
      demonstrate that insulin-like growth factor 1 receptor (IGF-1R) can be regulated
      by let-7a and let-7f. MTT assay confirmed that chondrocyte proliferation was
      inhibited by let-7a and let-7f mimics. In contrast, transfection of let-7a and
      let-7f inhibitors increased chondrocyte proliferation, indicating that inhibitors
      can competitively bind to endogenous miRNA, reducing the inhibitory effect of
      miRNA. Moreover, western blotting analysis further identified that let-7a and let
      7f mimics suppressed IGF-1R expression, and that let-7a and let-7f inhibitors
      increased the expression level of IGF-1R. Taken together, our study demonstrates
      the important roles of let-7a and let-7f in antler proliferation and its
      potential application in antler development. let-7a and let-7f may represent
      novel regulatory factors of IGF-1R expression in deer antler.

PMID- 24294914
TI  - Severe Kawasaki disease in a 3-month-old patient: a case report.
AB  - BACKGROUND: Kawasaki disease is a multi-system vasculitis which usually occurs in
      children under 5 years of age. In infants under three months of age, it is very
      rare and usually associated with a high incidence of incomplete or atypical
      forms, often unresponsive to treatment. This condition increases the risk of
      cardiovascular complications such as coronary artery aneurysms. CASE
      PRESENTATION: We describe a 3-month-old infant who developed early and severe
      aneurysms in three coronary arteries despite a timely administration of
      intravenous immunoglobulins, followed by three days of intravenous
      methylprednisolone. CONCLUSION: This case report underlines that the development
      of coronary artery aneurysm correlates with a delayed diagnosis and treatment,
      incomplete or atypical forms of the disease, and additionally the severity of
      clinical presentation, especially in cases of very young infants below 3 months
      of age. Our case is notable because of the very young age of the patient, the
      severity of clinical presentation with an early development of coronary artery
      aneurysms and the unresponsiveness to the therapy.

PMID- 24294915
TI  - Distractor repetitions retrieve previous responses and previous targets:
      experimental dissociations of distractor-response and distractor-target bindings.
AB  - Even an irrelevant distractor stimulus is integrated into event files.
      Subsequently repeating the distractor triggers retrieval of the event file;
      however, an unresolved issue concerns the question of what is retrieved by the
      distractor. While recent studies predominantly assume that the distractor
      retrieves the previous response, it is also possible that distractor repetition
      triggers retrieval of the previous target stimulus. In 3 experiments, we
      dissociated distractor-response and distractor-target binding processes using a
      sequential distractor-to-distractor repetition paradigm. In Experiment 1,
      response relation and target relation were manipulated orthogonally; results
      yielded independent evidence for both mechanisms. Experiment 2 provided distinct
      evidence for distractor-target binding and retrieval by avoiding response
      repetitions of any kind. Experiment 3 provided distinct evidence for distractor
      response binding and retrieval by eliminating target stimuli. We conclude that
      both distractor-target and distractor-response binding reflect independent
      processes in the service of behavior automatization.

PMID- 24294916
TI  - Cognitive advantages and disadvantages in early and late bilinguals.
AB  - Previous research has documented advantages and disadvantages of early
      bilinguals, defined as learning a 2nd language by school age and using both
      languages since that time. Relative to monolinguals, early bilinguals manifest
      deficits in lexical access but benefits in executive function. We investigated
      whether becoming bilingual after childhood (late bilinguals) can produce the
      cognitive advantages and disadvantages typical of early bilinguals. Participants
      were 30 monolingual English speakers, 30 late English-Spanish bilinguals, and 30
      early Spanish-English bilinguals who completed a picture naming task (lexical
      access) and an attentional network task (executive function). Late and early
      bilinguals manifested equivalent cognitive effects in both tasks, demonstrating
      lexical access deficits and executive function benefits. These findings provide
      support for the hypothesis that cognitive effects associated with bilingualism
      arise as the result of proficient, habitual use of 2 languages and not of
      developmental changes associated with becoming bilingual during childhood.

PMID- 24294917
TI  - Individual differences in contextual storage: evidence from the list-strength
      effect.
AB  - Strengthening some items in a list of words impairs free recall of the remaining
      items in the list-a phenomenon known as the list-strength effect (LSE; e.g.,
      Tulving & Hastie, 1972). Research indicates that whether the LSE is observed
      depends on the nature of the strengthening manipulation, and the effect is
      attributed to the enhancement of the contextual information in the memory trace
      of the items (e.g., Malmberg & Shiffrin, 2005). We investigated the magnitude of
      the LSE as a function of individual differences in working memory capacity (WMC).
      The findings indicate that low-WMC participants do not show the LSE, suggesting
      that they do not accumulate as much contextual information in the memory trace as
      the remaining participants do. These results suggest that the low-spans' deficits
      in utilizing contextual cues during retrieval (e.g., Spillers & Unsworth, 2011)
      could be partly linked to their deficits in encoding and storing contextual
      information. Implications for global theories of memory are discussed.

PMID- 24294918
TI  - Activation of lexical and semantic representations without intention along GPC
      sublexical and orthographic-lexical reading pathways in a Stroop paradigm.
AB  - Dual route models of reading suggest there are 2 pathways for reading words: an
      orthographic-lexical pathway, used to read familiar regular words and exception
      words, and a grapheme-to-phoneme-conversion-(GPC)-sublexical pathway, used to
      read unfamiliar regular words, pseudohomophones (PHs), and nonwords. It is
      unclear, however, whether PHs activate lexical and semantic representations
      without intention in the GPC-sublexical pathway to the same extent as words along
      the orthographic-lexical pathway. The present study explored this by introducing
      a novel condition, color pseudohomophone associates (CPHAs; e.g., "skigh"), in 3
      experiments using the Stroop paradigm. Experiment 1 examined 4 types of stimuli:
      color words (CWs), color word associates (CWAs), color PHs (CPHs), and color PH
      associates (CPHAs), in a mixed list context. Significant Stroop effects were
      found for all 4 types of stimuli. To ensure the robustness of this effect,
      Experiment 2 was conducted using pure list contexts whereby participants received
      only word stimuli (e.g., CWs, CWAs) or only PH stimuli (e.g., CPHs, CPHAs). The
      results replicated those of Experiment 1, suggesting that CPHAs activate lexical
      and semantic representations without intention in the GPC-sublexical pathway.
      Experiment 3 added 2 novel conditions: color exception word associates (which can
      only be pronounced correctly using the orthographic-lexical pathway) to compare
      the effects obtained with color exception PH associates (which rely on the GPC
      sublexical pathway for correct pronunciation). Stroop effects of similar
      magnitude were found for both types of stimuli, suggesting lexical and semantic
      representations are accessed without intention in either reading pathway to a
      similar degree. Implications for models of reading are discussed.

PMID- 24294919
TI  - Polyacrylate microspheres for tunable fluorimetric zinc ions sensor.
AB  - A novel concept of optical fluorimetric sensing using polymeric microspheres is
      explored on example of zinc ions sensors. The novel approach proposed uses the
      advantage of concomitant presence in a microsphere of two compounds: a receptor,
      fluorescently silent complexing ligand and an optical transducer, fluorescent
      compound. Binding of the analyte by the ligand affects its absorption spectrum,
      leading to decrease of the free ligand absorption and increase of complex
      absorption band. The decrease of free ligand absorption exposes emission of the
      transducer, yielding increase in fluorescence intensity on analyte concentration
      increase. This approach was verified experimentally using Zn(2+) as a model
      analyte, the fluorimetric sensor obtained uses 1-(2-pyridylazo)-2-naphthol (PAN)
      as analyte sensitive receptor and pyrene as optical transducer. In the absence of
      zinc ions in the sample emission of pyrene embedded in the spheres was
      significantly quenched, whereas increase of Zn(2+) ions concentration in the
      sample resulted in dependence of fluorescence intensity on logarithm of zinc ions
      concentration in extraordinary wide range, from 10(-7) to 0.1 M. The response
      mechanism was explained by surface accumulation of zinc ion-PAN complex on the
      microsphere/sample solution interface. It was also shown that introduction of
      cation-exchanging sites to the microspheres significantly alters the responses
      pattern leading to high sensitivity over relatively limited concentration range
      (3-4 orders of magnitude). In the latter case the observed responses can be tuned
      to occur in chosen concentration range, simply by adjusting sample pH. 

PMID- 24294921
TI  - Self-harm in young adolescents (12-16 years): onset and short-term continuation
      in a community sample.
AB  - BACKGROUND: To investigate the prevalence of self-harm in young adolescents and
      factors associated with onset and continuity over a one year period. METHOD:
      Prospective longitudinal study. Participants were young adolescents (n = 3964)
      aged 12-16 years attending 8 secondary schools in the Midlands and South West of
      England. RESULTS: Over a one year period 27% of young adolescents reported
      thoughts of self-harm and 15% reported at least one act of self-harm. Of those
      who self-harmed, less than one in five (18%) had sought help for psychological
      problems of anxiety or depression. Compared with boys, girls were at increased
      risk of developing thoughts (OR 1.61, 95% CI 1.26-2.06) and acts (OR 1.40, 95% CI
      1.06-1.84) of self-harm, particularly amongst those girls in school year 9 (aged
      13/14, thoughts adjusted Odds Ratio (aOR) 1.97, 95% CI 1.27-3.04; acts aOR 2.59,
      95% CI 1.52-4.41). Of those reporting thoughts of self-harm at baseline, 60% also
      reported these thoughts at follow-up. Similarly 55% of those who reported an act
      of self-harm at baseline also reported that they had self-harmed at follow-up.
      Insecure peer relationships increased the likelihood that boys and girls would
      develop self-harming behaviours, as did being bullied for boys. Low mood was
      associated with the development of self-harming thoughts and behaviours for boys
      and girls, whilst a strong sense of school membership was associated with a
      reduced risk of developing thoughts of self-harm for boys and increased the
      likelihood of self-harming thoughts and behaviours ceasing for girls. CONCLUSION:
      Self harm in young adolescents is common with one in four reporting self-harming
      thoughts and one in six engaging in self-harming behaviour over a one year
      period. Self-harm is already established by 12/13 years of age and for over half
      of our sample, self-harming thoughts and behaviour persisted over the year.
      Secure peer and strong school relationships were associated with less self-harm.
      Few seek help for psychological problems, suggesting a need to increase awareness
      amongst all professionals who work with young adolescents about self-harm and
      associated risk factors.

PMID- 24294922
TI  - Ewing's sarcoma cancer stem cell targeted therapy.
AB  - Ewing's sarcoma (ES) family of tumors (ESFTs) are round cell tumors of bone and
      soft tissues, afflicting children and young adults. This review summarizes the
      present findings about ES cancer stem cell (CSC) targeted therapy: prognostic
      factors, chromosomal translocations, initiation, epigenetic mechanisms, candidate
      cell of ES origin (Mesenchymal stem cells (MSCs) and Neural crest stem cells
      (NCSCs)). The ES CSC model, histopathogenesis, histogenesis, pathogenesis, ES
      mediated Hematopoietic stem progenitor cells (HSPCs) senescence are also
      discussed. ESFTs therapy is reviewed concerning CSCs, radiotherapy, risk of
      subsequent neoplasms, stem cell (SC) support, promising therapeutic targets for
      ES CSCs (CSC markers, immune targeting, RNAi phenotyping screens, proposed new
      drugs), candidate EWS-FLI1 target genes and further directions (including human
      embryonic stem cells (hESCs)). Bone marrow-derived human MSCs are permissive for
      EWS-FLI1 expression with transition to ESFT-like cellular phenotype. ESFTs are
      genetically related to NCSC, permissive for EWS-FLI1 expression and susceptible
      to oncogene-induced immortalization. Primitive neuroectodermal features and MSC
      origin of ESFTs provide a basis of immune targeting. The microRNAs profile of ES
      CSCs is shared by ESCs and CSCs from divergent tumor types. Successful
      reprogramming of differentiated human somatic cells into a pluripotent state
      allows creation of patient- and disease-specific SCs. The functional role of
      endogenous EWS at stem cell level on both senescence and tumorigenesis is a link
      between cancer and aging. The regulatory mechanisms of oncogenic activity of EWS
      fusions could provide new prognostic biomarkers, therapeutic opportunities and
      tumor-specific anticancer agents against ESFTs.

PMID- 24294920
TI  - Cellular biochemistry methods for investigating protein tyrosine phosphatases.
AB  - SIGNIFICANCE: The protein tyrosine phosphatases (PTPs) are a family of proteins
      that play critical roles in cellular signaling and influence many aspects of
      human health and disease. Although a wealth of information has been collected
      about PTPs since their discovery, many questions regarding their regulation and
      function still remain. CRITICAL ISSUES: Of particular importance are the
      elucidation of the biological substrates of individual PTPs and understanding of
      the chemical and biological basis for temporal and spatial resolution of PTP
      activity within a cell. RECENT ADVANCES: Drawing from recent advances in both
      biology and chemistry, innovative approaches have been developed to study the
      intracellular biochemistry and physiology of PTPs. We provide a summary of PTP
      tailored techniques and approaches, emphasizing methodologies to study PTP
      activity within a cellular context. We first provide a discussion of methods for
      identifying PTP substrates, including substrate-trapping mutants and synthetic
      peptide libraries for substrate selectivity profiling. We next provide an
      overview of approaches for monitoring intracellular PTP activity, including a
      discussion of mechanistic-based probes, gel-based assays, substrates that can be
      used intracellularly, and assays tied to cell growth. Finally, we review
      approaches used for monitoring PTP oxidation, a key regulatory pathway for these
      enzymes, discussing the biotin switch method and variants of this approach, along
      with affinity trapping techniques and probes designed to detect PTP oxidation.
      FUTURE DIRECTIONS: Further development of approaches to investigate the
      intracellular PTP activity and functions will provide specific insight into their
      mechanisms of action and control of diverse signaling pathways.

PMID- 24294923
TI  - Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase.
AB  - Acetyl-CoA carboxylase (ACC) is a target of interest for the treatment of
      metabolic syndrome. Starting from a biphenyloxadiazole screening hit, a series of
      piperazine oxadiazole ACC inhibitors was developed. Initial pharmacokinetic
      liabilities of the piperazine oxadiazoles were overcome by blocking predicted
      sites of metabolism, resulting in compounds with suitable properties for further
      in vivo studies. Compound 26 was shown to inhibit malonyl-CoA production in an in
      vivo pharmacodynamic assay and was advanced to a long-term efficacy study.
      Prolonged dosing with compound 26 resulted in impaired glucose tolerance in diet
      induced obese (DIO) C57BL6 mice, an unexpected finding. 

PMID- 24294924
TI  - Airway oxidative stress in chronic cough.
AB  - BACKGROUND: The mechanisms of chronic cough are unclear. Many reactive oxygen
      species affect airway sensory C-fibres which are capable to induce cough. Several
      chronic lung diseases are characterised by cough and oxidative stress. In asthma,
      an association between the cough severity and airway oxidative stress has been
      demonstrated. The present study was conducted to investigate whether airway
      oxidative stress is associated with chronic cough in subjects without chronic
      lung diseases. METHODS: Exhaled breath condensate samples were obtained in 43 non
      smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria
      included a doctor's diagnosis of any lung disorders and any abnormality in lung x
      ray. The concentration of 8-isoprostane was measured. In addition, the patients
      filled in Leicester Cough Questionnaire and underwent hypertonic saline cough
      provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide
      measurement, and histamine airway challenge. In a subgroup of patients the
      measurements were repeated during 12 weeks' treatment with inhaled budesonide,
      800 ug/day. RESULTS: The 8-isoprostane concentrations were higher in the cough
      patients than in the healthy subjects (24.6 +/- 1.2 pg/ml vs. 10.1 +/- 1.7 pg/ml,
      p = 0.045). The 8-isoprostane concentration was associated with the Leicester
      Cough Questionnaire total score (p = 0.044) but not with the cough sensitivity to
      saline or other tests. Budesonide treatment did not affect the 8-isoprostane
      concentrations. CONCLUSIONS: Chronic cough seems to be associated with airway
      oxidative stress in subjects with chronic cough but without chronic lung
      diseases. This finding may help to develop novel antitussive drugs. TRIAL
      REGISTRATION: The study was registered in ClinicalTrials.gov database
      (KUH5801112), identifier NCT00859274.

PMID- 24294925
TI  - Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer
      testing, bioavailability and biodistribution study.
AB  - BACKGROUND: The natural flavonoid fisetin has shown anticancer properties but its
      in vivo administration remains challenging due its poor aqueous solubility and
      extensive in vivo metabolism. This juncture demands an effective, controlled
      release and safe formulation of fisetin would be a significant advance for the
      treatment of cancer. OBJECTIVES: Nanocochleates are unique lipid-based
      supramolecular assemblies composed of a negatively charged phospholipid and a
      divalent cation. The aim was to develop and evaluate fisetin-loaded
      nanocochleates to improve its therapeutic efficacy. Using the trapping method,
      fisetin-loaded dimyristoylphosphatidylcholine liposomal vesicles were converted
      into nanocochleates by the action of Ca(2+) ions. These nanocochleates were
      further evaluated for physicochemical, in vitro anticancer and haemolysis,
      pharmacokinetics and tissue distribution study in mice. RESULTS: Stable rolled-up
      layers as well as elongated structure of nanocochleates possessing particle size
      and encapsulation efficiency (EE) of 275 + 4 nm and 84.31 +/- 2.52%, respectively
      were obtained. Nanocochleates demonstrated safety and a sustained release of
      fisetin at physiological pH. A 1.3-fold improvement in vitro anticancer towards
      human breast cancer MCF-7 cells was observed. Pharmacokinetics studies in mice
      revealed that nanocochleates injected intraperitonially showed a 141-fold higher
      relative bioavailability. Moreover, a low tissue distribution was observed.
      CONCLUSION: Developed nanocochleates markedly improved anticancer efficacy,
      bioavailability and safety of fisetin. The nanocochleates technology would
      facilitate the administration of this flavonoid in the clinical setting. AREAS
      COVERED: In this research article, we focused on lipid-based supramolecular
      assembly 'nanocochleates' composed of negatively charged phospholipids and
      divalent cation as drug carrier for systemic delivery system and discussed their
      formulations, optimisation, characterization, in vitro and in vivo performance.

PMID- 24294926
TI  - Potential biomarker of subjective quality of life: prefrontal activation
      measurement by near-infrared spectroscopy.
AB  - Recently, there has been growing emphasis on enhancing subjective quality of life
      (QOL), in addition to treating symptoms or extending one's life. However, the
      neurobiological basis of subjective QOL is unknown. To illuminate the neural
      substrates that inform subjective QOL, the association between prefrontal
      function and subjective QOL was explored in 72 healthy volunteers (40 women and
      32 men; age, 45.1 +/- 20.1 y), using 52-channel near-infrared spectroscopy
      (NIRS), a portable neuroimaging device that can measure brain function in a less
      constrained condition. Results confirmed that subjective QOL was positively
      correlated with prefrontal hemodynamic response during a cognitive task and that
      subjective satisfaction regarding social relationships and in the physical
      domains were cardinal contributors to the association. These findings suggest
      that subjective QOL has possible involvement in prefrontal function and that NIRS
      potentially plays a role as a biological marker of subjective QOL.

PMID- 24294929
TI  - Does premarital education decrease or increase couples' later help-seeking?
AB  - Interventions intended to prevent relationship distress are expected to enhance
      relationship satisfaction and, in turn, reduce the need for later couples
      counseling. We test this prediction against an alternative possibility:
      participation in preventive interventions may operate as a gateway for later help
      seeking, paradoxically increasing receipt of later couples counseling. A cross
      sectional study of 2,126 married individuals examined whether participation in
      premarital education covaried inversely or directly with couples counseling.
      Consistent with the gateway hypothesis, receiving premarital education covaried
      with an increased likelihood of receiving couples counseling. The association
      between receipt of premarital education and pursuit of couples counseling was
      moderated by demographic indicators, with the association being stronger for
      African Americans and for individuals with lower incomes and less formal
      education. Encouraging the use of premarital interventions may increase the use
      of therapeutic interventions later in the relationship, especially among high
      risk populations.

PMID- 24294927
TI  - Adolescent gender-related abuse, androphilia, and HIV risk among transfeminine
      people of color in New York City.
AB  - Public health research has indicated extremely high HIV seroprevalence (13%-63%)
      among low-income transfeminine people of color of African, Latina, and Asian
      descent living in the U.S. This article combines two data sets. One set is based
      on an ethnographic study (N = 50, 120 hours of participant observation). The
      other set is based on a longitudinal quantitative study (baseline N = 600, N =
      275 followed for 3 years). Transfeminine people of color are much more likely to
      be androphilic and at high HIV risk. A greater understanding of adolescent gender
      related abuse and trauma-impacted androphilia contributes toward a holistic
      conceptual model of HIV risk. A theoretical model is proposed that incorporates
      findings from both studies and integrates sociostructural, interpersonal, and
      intrapsychic levels of HIV risk.

PMID- 24294928
TI  - Increased expression of vascular endothelial growth factor attenuates contusion
      necrosis without influencing contusion edema after traumatic brain injury in
      rats.
AB  - To clarify the role of vascular endothelial growth factor (VEGF) in the formation
      of contusion edema and necrosis after traumatic brain injury, we examined the
      time course of changes in the VEGF expression (enzyme-linked immunosorbent
      assay), cerebrovascular permeability (extravasation of Evans blue), and water
      content (dry-wet weight method) of the contused brain tissue in a cortical impact
      injury model using rats. In addition, we tested the effects of administration of
      bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular
      permeability and water content of the contused brain tissue, as well as the
      neurological deficits (rota rod test) and volume of contusion necrosis. Increased
      VEGF expression was maximal at 72 h after injury (p<0.003). Increases in
      cerebrovascular permeability and water content, however, became maximal within 24
      h (p<0.001) after injury (p<0.01), respectively. Administration of bevacizumab
      did not influence these changes in cerebrovascular permeability and water
      content, but led to a significant rise in the neurological deficits at 72 h-14
      days (p<0.05 or 0.01) and the volume of contusion necrosis at 21 days (p<0.001)
      after injury. These findings suggest that increased expression of VEGF after
      injury does not contribute to the formation of contusion edema, but attenuates
      the formation of contusion necrosis. This is probably because of an increased
      angiogenesis and improved microcirculation in the areas surrounding the core of
      contusion.

PMID- 24294931
TI  - Patterns of depressive parenting: why they occur and their role in early
      developmental risk.
AB  - This study examined subgroups of depressed mothers who differ on their intrusive
      and withdrawn behavior. It explored the stability of these differences, why they
      occur, and their role in children's early developmental risk. With 6- to 24-month
      data from 1,364 dyads, latent class analysis identified 3 stable patterns of
      early parenting among mothers consistently above clinical thresholds on
      depressive symptoms (n = 159): 2 low-functioning patterns (high intrusive, high
      intrusive/high withdrawn) and 1 high-functioning pattern (low intrusive/low
      withdrawn). Low-functioning depressed mothers were no more depressed than high
      functioning depressed mothers, but lacked personal resources and were in low
      support, high-stress contexts. Differences in their children's development over
      the first 2 years appeared to depend primarily on demographic risk. By 36 months,
      however, stable differences in depressed mothers' patterns of intrusive and
      withdrawn parenting-independent of demographic risk-predicted cognitive and
      language development, the quality of the relationship with the mother
      (attachment, responsiveness to mothers), and socioemotional competence. Children
      of high-functioning depressed mothers were not significantly different from
      children of nondepressed mothers in cognitive and language development and in
      attachment and responsiveness to the mother, but displayed more behavior problems
      and less social competence. Findings reveal stable differences in parenting
      within a sample of depressed mothers, support a stress and coping perspective on
      why these differences occur, and demonstrate their potential role in determining
      the risk children of depressed mothers face over the first 3 years.

PMID- 24294932
TI  - Coparenting in immigrant Chinese Canadian families: the role of discrepancies in
      acculturation and expectations for adolescent assistance.
AB  - For immigrant families, differential acculturation between mothers and fathers
      may present challenges to parenting adolescents. The current study investigated
      the concurrent relations among discrepancies in parental acculturation,
      discrepancies in parental expectations for adolescents, and coparenting quality
      with a sample of 162 married immigrant Chinese Canadian couples with adolescents
      (mean age = 14.94 years; SD = 1.73). Acculturation was assessed as parents'
      behavioral involvement in both Canadian and Chinese cultures. As predicted,
      mother-father differences in acculturation (in relation to both cultures) were
      related to discrepant expectations for how much adolescents should assist the
      family. Further, mother-father differences in Chinese acculturation were related
      to fathers' perceptions of a poorer coparenting relationship. Finally, this
      relation was partially mediated by discrepant parental expectations for
      adolescent assistance. Implications for parenting roles, enculturation, family
      dynamics, and intervention are considered.

PMID- 24294934
TI  - Disappointment's sting is greater than help's balm: quasi-signal detection of
      daily support matching.
AB  - The optimal matching model of support suggests that supportive behaviors are
      effective when they match recipients' needs or goals. In 2 studies, we used quasi
      signal detection to test this model. Specifically, we simultaneously modeled the
      associations of affective and relational outcomes with matching ("hits"),
      underprovision ("misses"), and overprovision ("false alarms") regarding emotional
      or practical support. In both studies (N = 44 and 38 couples, respectively), both
      partners in committed relationships reported daily receipt of and desire for
      support, as well as moods and relational outcomes for 21 days. Emotional (but not
      practical) matching was associated with favorable relational outcomes only;
      overprovision had a minimal effect. In contrast, both emotional and practical
      support underprovision were associated with adverse outcomes, both affective and
      relational in nature. Study 2 ruled out the possibility that stress is the sole
      mechanism responsible for the adverse effects of underprovision, and found
      evidence for another, relational mechanism; specifically, the results documented
      the role of perceived partner responsiveness as a mechanism mediating the
      deleterious effect of underprovision.

PMID- 24294933
TI  - Internalizing and externalizing symptoms in young children exposed to intimate
      partner violence: examining intervening processes.
AB  - Children's emotion dysregulation, children's appraisals, maternal psychological
      functioning, and harsh discipline were investigated as potential mediators in the
      putative link between exposure to intimate partner violence and poor child
      outcomes. Participants included 132 children ages 6-8 and their mothers who had
      been enrolled in a longitudinal study of parenting and children's social
      development. The mothers were receiving some form of government-based economic
      assistance or other social services, and were currently involved in a romantic
      relationship. Results of structural equation modeling indicated children's
      emotion dysregulation mediated the links between exposure to intimate partner
      violence (IPV) and both internalizing and externalizing problems. Harsh
      discipline mediated the link between exposure to IPV and externalizing, but not
      internalizing, symptoms. Child appraisals and maternal psychological functioning
      mediated the link between exposure to IPV and internalizing, but not
      externalizing, symptoms.

PMID- 24294935
TI  - Mutations and seeding of amylin fibril-like oligomers.
AB  - Seeding a protein solution with preformed fibrils can dramatically enhance the
      growth rate of amyloids. As the seeds do not need to be of the same protein,
      seeding may account for the observed correlations between amyloid diseases. In an
      effort to understand better the molecular mechanisms behind cross seeding we have
      studied in silico the effect of mutations on the seeding of amylin fibrils. Our
      investigations of the structural stability of decamers of wild type amylin
      peptides, of Y37L mutants, and of heteroassemblies of wild-type and mutant amylin
      molecules show that the experimentally observed efficient cross seeding can be
      explained based on similarity in fibril structure of components. We find that
      amyloids with similar side chains packing at the beta-sheet interface are
      structurally compatible, acting as a good template for the congruent
      incorporation of homologues peptides. In the Y37L mutants, lack of tyrosine
      specific interactions causes significant higher flexibility of the C terminal
      than observed in the wild-type fibril. This effects elongation of the mutant
      fibril leading to the longer lag times during aggregation that are observed in
      experiments. Our study gives guidelines for the design of ligands that could
      stabilize amylin fibrils. 

PMID- 24294936
TI  - An efficient, modular approach for the synthesis of (+)-strictifolione and a
      related natural product.
AB  - An efficient, library amenable, "pot economical" total synthesis of (+)
      strictifolione and the related natural product, (6R)-6[(E,4R,6R)-4,6-dihydroxy-10
      phenyl-1-decenyl]-5,6-dihydro-2H-2-pyrone, are reported. This modular approach
      takes advantage of two consecutive phosphate tether-mediated, one-pot, sequential
      protocols, followed by a final cross metathesis to deliver both antifungal
      natural products in a three-pot process from the respective enantiomeric (R,R)-
      and (S,S)-trienes with minimal purification. A salient feature of this route is
      that additional protecting groups are not required as a result of the orthogonal
      protecting- and leaving-group properties innate to phosphate triesters. 

PMID- 24294937
TI  - Relative risk for concussions in young female soccer players.
AB  - The objective of this study was to determine the relative risk and reported
      symptoms of concussions in 11- to 13-year-old, female soccer players. For this, a
      survey to compare the reported incidence of concussion in age-matched female
      soccer players to nonsoccer players was performed. The survey included 342 girls
      between the ages of 11 and 13: 195 were involved in an organized soccer team and
      147 were not involved in organized soccer but were allowed to participate in any
      other sport or activity. A total of 94 of the 195 soccer players, or 48%,
      reported at least one symptom consistent with a concussion. The most prevalent
      symptom for these girls was headache (84%). A total of 34 of the 147 nonsoccer
      players, or 23%, reported at least one symptom consistent with a concussion in
      the previous six months. These results determined that the relative risk of
      probable concussions among 11- to 13-year-old, female soccer players is 2.09 (p <
      .001, alpha = .05, CI = 95%). This demonstrates that the relative risk of
      probable concussions in young female soccer players is significantly higher than
      in a control group of nonsoccer players of the same sex and age. 

PMID- 24294939
TI  - Modulation of intestinal folate absorption by erythropoietin in vitro.
AB  - Besides the direct stimulation of erythropoiesis, erythropoietin (EPO) therapy in
      renal anemia may also play a regulatory role in maintaining the homeostasis of
      hematopoietic nutrients. It has been reported that EPO can stimulate intestinal
      iron absorption. However, the involvement of EPO in intestinal folate absorption
      remains elusive. The objective of this study was to investigate the effect of EPO
      on intestinal transport of folate in vitro and to elucidate the possible
      mechanism(s) involved in this regulation. Transport assays of folic acid were
      performed in Caco-2 monolayers treated with EPO. The effect of EPO on the
      expression of transporters involved in the folate absorption was investigated.
      The possible involvement of three main EPO signaling pathways, the janus protein
      tyrosine kinase 2 (JAK-2) pathway, extracellular signal regulated kinases (ERK)
      pathway, and phosphatidylinositol 3 kinase/Akt (PI3K/Akt) pathway, in the
      transporter regulation was explored. The absorptive flux (apical to basolateral)
      of folic acid was enhanced by EPO treatment in a dose-dependent manner, which was
      companied with the significant up-regulation of reduced folate carrier (RFC) and
      apical proton coupled folate transporter (PCFT). The efflux (basolaterial to
      apical) of folic acid was enhanced only by the high dose of EPO treatment, which
      was associated with the significant up-regulation of apical multidrug resistance
      associated protein 2 (MRP2). The expression levels of all of these transporters
      were up-regulated by EPO treatment in a dose- and time-dependent manner.
      Transporter expression in response to blocking EPO induced activation of JAK-2,
      ERK, and PI3K/Akt was changed to a different extent. As a conclusion, intestinal
      folate absorption was enhanced by EPO treatment in vitro. Our findings provided
      direct evidence to establish the correlation between EPO and folate homeostasis. 

PMID- 24294938
TI  - Review of insecticide resistance and behavioral avoidance of vectors of human
      diseases in Thailand.
AB  - Physiological resistance and behavioral responses of mosquito vectors to
      insecticides are critical aspects of the chemical-based disease control equation.
      The complex interaction between lethal, sub-lethal and excitation/repellent
      ('excito-repellent') properties of chemicals is typically overlooked in vector
      management and control programs. The development of "physiological" resistance,
      metabolic and/or target site modifications, to insecticides has been well
      documented in many insect groups and disease vectors around the world. In
      Thailand, resistance in many mosquito populations has developed to all three
      classes of insecticidal active ingredients currently used for vector control with
      a majority being synthetic-derived pyrethroids. Evidence of low-grade insecticide
      resistance requires immediate countermeasures to mitigate further intensification
      and spread of the genetic mechanisms responsible for resistance. This can take
      the form of rotation of a different class of chemical, addition of a synergist,
      mixtures of chemicals or concurrent mosaic application of different classes of
      chemicals. From the gathered evidence, the distribution and degree of
      physiological resistance has been restricted in specific areas of Thailand in
      spite of long-term use of chemicals to control insect pests and disease vectors
      throughout the country. Most surprisingly, there have been no reported cases of
      pyrethroid resistance in anopheline populations in the country from 2000 to 2011.
      The precise reasons for this are unclear but we assume that behavioral avoidance
      to insecticides may play a significant role in reducing the selection pressure
      and thus occurrence and spread of insecticide resistance. The review herein
      provides information regarding the status of physiological resistance and
      behavioral avoidance of the primary mosquito vectors of human diseases to
      insecticides in Thailand from 2000 to 2011. 

PMID- 24294941
TI  - Cobalt fluorocarbenes: cycloaddition reactions with tetrafluoroethylene and
      reactivity of the perfluorometallacyclic products.
AB  - Cobalt fluorocarbene complexes CpCo(?CFR(F))(PPh2Me) (Cp = eta(5)-C5H5, R(F) = F
      or CF3) react with tetrafluoroethylene to give the metallacyclobutanes
      CpCo(kappa(2)-CFR(F)CF2CF2-)(PPh2Me) in the first examples of cycloaddition
      reactions between perfluoroalkenes and metal perfluorocarbenes. The metallacyclic
      products undergo a variety of reactions upon activation of the C-F bonds,
      including Bronsted acid-catalyzed C-F/Co-C scrambling. Implications for metal
      catalyzed metathesis and polymerization of perfluoroalkenes are discussed. 

PMID- 24294940
TI  - Patterns of risk for anxiety-depression amongst Vietnamese-immigrants: a
      comparison with source and host populations.
AB  - BACKGROUND: Studies suggest that immigrants have higher rates of anxiety
      depression than compatriots in low-middle income countries and lower rates than
      populations in host high income countries. Elucidating the factors that underlie
      these stepwise variations in prevalence may throw new light on the pathogenesis
      of anxiety-depressive disorders globally. This study aimed to examine whether
      quantitative differences in exposure to, or the interaction between, risk factors
      account for these anxiety-depression prevalence differences amongst immigrant
      relative to source and host country populations. METHODS: Multistage population
      mental health surveys were conducted in three groups: 1) a Vietnamese-immigrant
      sample settled in Australia (n = 1161); 2) a Vietnamese source country sample
      residing in the Mekong Delta region (n = 3039); 3) an Australian-born host
      country sample (n = 7964). Multivariable logistic regression analyses compared
      risk factors between the Vietnamese-immigrant group and: 1) the Mekong Delta
      Vietnamese; and 2) the Australian-born group. Twelve month anxiety-depression
      diagnoses were the main outcome measures, derived from the Composite
      International Diagnostic Interview (CIDI), supplemented by an indigenously
      derived measure - the Phan Vietnamese Psychiatric Scale (PVPS) in both Vietnamese
      groups. RESULTS: The 12-month prevalence of anxiety-depression showed a stepwise
      increase across groups: Mekong Delta Vietnamese 4.8%; Vietnamese-immigrants 7.0%;
      Australian-born 10.2%. The two Vietnamese populations showed a similar risk
      profile with older age, exposure to potentially traumatic events (PTEs), multiple
      physical illnesses and substance use disorder (SUD) being associated with anxiety
      depression, with the older Vietnamese-immigrants reporting greater exposure to
      these factors. The interaction between key risk factors differed fundamentally
      when comparing Vietnamese-immigrant and Australian-born samples. Age emerged as
      the major discriminator, with young Vietnamese-immigrants exhibiting particularly
      low rates of anxiety-depression. CONCLUSIONS: The findings reported here suggest
      that core risk factors for anxiety-depression may be universal, but their
      patterning and interaction may differ according to country-of-origin. The study
      also highlights the importance of including both standard international and
      culturally-specific measures to index cross-cultural manifestations of common
      mental disorders.

PMID- 24294942
TI  - Polyphenols: a nutraceutical approach against diseases.
AB  - Polyphenols are abundant in red grapes and in their derived products, amongst
      other natural food sources. These compounds are associated with the prevention of
      diseases caused by oxidative stress. The present review discusses the action of
      grape polyphenols against diseases and the new polyphenol-rich products developed
      to be used as nutraceuticals. Grape polyphenols demonstrated effects such as
      maintenance of endothelial function, increase in antioxidant capacity and
      protection against LDL oxidation. Recent patents regarding polyphenols show a
      tendency to use a right-on-target approach and the new patented products are
      aiming at preventing and treating specific diseases. 

PMID- 24294943
TI  - Recent innovations in the area of edible films and coatings.
AB  - Edible films/coatings have been considered as one of the potential technologies
      that can be used to increase the storability of foods and to improve the existent
      packaging technology, helping to ensure the microbial safety and the preservation
      of food from the influence of external factors. Innovations constantly appear in
      food packaging, always aiming at creating a more efficient quality preservation
      system while improving foods' attractiveness and marketability. The utilization
      of renewable sources for packaging materials, such as hydrocolloids and lipids
      from biological origin, is one the main trends of the industry. These films
      should have acceptable sensory characteristics, appropriate barrier properties
      (CO2, O2, water, oil), microbial, biochemical and physicochemical stability, they
      should be safe, and produced by simple technology in low cost. Also they can act
      as effective carrier for antioxidant, flavor, color and nutritional or anti
      microbial additives. Nowadays, a great discussion exists about the potential
      applications of edible films/coatings on food products. The general trend is to
      find the correct combination between the food product and the edible
      film/coating, which will ensure the success of the technology. 

PMID- 24294944
TI  - Dual drug-eluting stents coated with multilayers of hydrophobic heparin and
      sirolimus.
AB  - Polymer coatings for stents are considered one of the key factors that lead to
      adverse cardiac events after coronary arterial stenting. This study presents a
      dual drug-eluting stent (DES) that is coated with multilayers of Duraflo heparin
      and sirolimus but containing no other organic polymers. The hydrophobic Duraflo
      heparin coating was used to improve the hemocompatibility of the stent and serve
      as a drug reservoir for the controlled release of sirolimus, thus avoiding
      inflammatory reactions induced by the conventional polymers. The Duraflo heparin
      and sirolimus were coated layer-by-layer onto the stent surface using a homemade
      spray-coating device. The drug loading amount can be easily controlled by
      adjusting the numbers of layers applied and the concentration of the drug
      solution, indicating the developed coating process is reproducible and well
      controlled. After balloon expansion, the coating did not crack or peel off, which
      demonstrates that the sirolimus/Duraflo heparin coating layers tightly adhere to
      the stent surface. The activated partial thromboplastin time (APTT) assay showed
      that the Duraflo heparin coating significantly prolonged the APTT from 27.3 +/-
      0.3 s to 69.7 +/- 6.2 s, demonstrating the anticoagulant ability of the coated
      stents. The dual DES exhibited a nearly linear sustained-release profile of
      Duraflo heparin and an initial burst release followed by a slow release of
      sirolimus. Less than 15% of heparin was released from the DES within 14 days,
      indicating the stent can maintain its antithrombotic surface for a long time.
      Because of the layer-by-layer structure, the most outer layer of Duraflo heparin
      coating may act as a diffusion barrier to retard sirolimus release from the
      stent. These results confirm that the dual DESs enable simultaneous delivery of
      antithrombotic and antiproliferative drugs and have potential for the treatment
      of coronary artery disease. 

PMID- 24294946
TI  - Quantitative bottom-up proteomics depends on digestion conditions.
AB  - Accurate quantification is a fundamental requirement in the fields of proteomics
      and biomarker discovery, and for clinical diagnostic assays. To demonstrate the
      extent of quantitative variability in measurable peptide concentrations due to
      differences among "typical" protein digestion protocols, the model protein, human
      serum albumin (HSA), was subjected to enzymatic digestion using 12 different
      sample preparation methods, and separately, was examined through a comprehensive
      timecourse of trypsinolysis. A variety of digestion conditions were explored
      including differences in digestion time, denaturant, source of enzyme, sample
      cleanup, and denaturation temperature, among others. Timecourse experiments
      compared differences in relative peptide concentrations for tryptic digestions
      ranging from 15 min to 48 h. A predigested stable isotope-labeled ((15)N) form of
      the full-length (HSA) protein, expressed in yeast was spiked into all samples
      prior to LC-MS analysis to compare yields of numerous varieties of tryptic
      peptides. Relative quantification was achieved by normalization of integrated
      extracted ion chromatograms (XICs) using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) by multiple-reaction monitoring (MRM) on a triple
      quadrupole (QQQ) MS. Related peptide fragmentation transitions, and multiple
      peptide charge states, were monitored for validation of quantitative results.
      Results demonstrate that protein concentration was shown to be unequal to tryptic
      peptide concentrations for most peptides, including so-called "proteotypic"
      peptides. Peptide release during digestion displayed complex kinetics dependent
      on digestion conditions and, by inference, from denatured protein structure.
      Hydrolysis rates at tryptic cleavage sites were also shown to be affected by
      differences in nearest and next-nearest amino acid residues. The data suggesting
      nonstoichiometry of enzymatic protein digestions emphasizes the often overlooked
      difficulties for routine absolute protein quantification, and highlights the need
      for use of suitable internal standards and isotope dilution techniques. 

PMID- 24294947
TI  - Inter-joint sharing of total support moments in the lower extremities during gait
      in narrow-heeled shoes of different heights.
AB  - The study aimed to investigate the influence of the base and height of shoe heels
      on the total support moment (Ms) and individual joint contributions during gait.
      Fifteen healthy females walked barefoot and with narrow-heeled shoes (heel
      heights: 3.9, 6.3 and 7.3 cm) while kinematic and kinetic data were measured.
      Compared with the barefoot condition, the subjects maintained unaltered Ms in the
      sagittal plane in shod conditions. This was achieved by increasing the knee
      extensor moment to compensate for the diminished ankle plantarflexor moments in
      medium and high heel conditions. In the frontal plane, subjects in shod
      conditions had to sustain an increased Ms for balance control during late single
      leg stance with increased knee abductor and ankle pronator moments as a result of
      the reduced base of the heels. The results will be helpful for future shoe
      designs to reduce fall risks and prevent relevant musculoskeletal problems.

PMID- 24294948
TI  - Endocervical and high vaginal quantitative fetal fibronectin in predicting
      preterm birth.
AB  - OBJECTIVE: Accurate prediction of spontaneous preterm birth (sPTB) is essential
      to target interventions. Fetal fibronectin (fFN) is a leading predictor. A
      quantitative fFN (qfFN) test has improved prediction, based on high vaginal swabs
      (HVS). It is not known how endocervical (ECS) fFN levels compare, or which has
      the best predictive value. Our principal aim was to determine the difference in
      fFN concentration between HVS and ECS and compare their ability to predict sPTB.
      METHODS: Asymptomatic high risk women (18(+0)-30(+0) weeks gestation) had
      secretions sampled from the endocervix (ECS) and vaginal fornix (HVS), analyzed
      by the quantitative fFN analyzer (Hologic). Mean concentrations were compared;
      ROC curves were calculated using area under the curve (AUC) for prediction of
      delivery <30 and 37 weeks. RESULTS: Mean HVS value was lower than ECS (80 ng/ml
      (SD142) versus 217 (SD 212) (p < 0.05). Predictive ability was similar: AUC of
      0.92 and 0.94, respectively, for prediction of sPTB < 37 and 0.84 and 0.82 for
      <30 weeks. CONCLUSIONS: Endocervical qfFN is higher than HVS and clinicians
      should avoid ECS if using traditional thresholds. ECS and HVS are both useful
      predictors, but require different threshold values. Further work is needed to
      determine whether ECS is a better and safe test to justify the difficulty in
      sampling.

PMID- 24294949
TI  - A socio-ecological model for unintentional injuries in minorities: a case study
      of Arab Israeli children.
AB  - Minority children have often been reported to be at high risk of injury. The
      higher levels of reported unintentional injuries among Arab children compared to
      Jewish children in Israel are mainly due to pedestrian traffic crashes, falls and
      burns. Arab children aged 1-4 years have a higher relative risk of injury
      compared to Jews. We suggest a socio-ecological model to explain these
      differences in risk based on individual, interpersonal, community and societal
      ecological levels of society. Each level is divided into social and physical
      environments and behaviour. Two main factors may contribute to the high rates of
      injury among Arab children: the quality of the physical environment in which the
      children live and play and the levels of child supervision. Socio-economic status
      may contribute to these differences at all ecological levels of society. This
      approach could be useful for researchers and practitioners to analyse similar
      issues in other communities and help develop appropriate interventions. 

PMID- 24294945
TI  - Reactive oxygen and nitrogen species in steatotic hepatocytes: a molecular
      perspective on the pathophysiology of ischemia-reperfusion injury in the fatty
      liver.
AB  - SIGNIFICANCE: Hepatic ischemia-reperfusion (IR) injury results from the temporary
      deprivation of hepatic blood supply and is a common side effect of major liver
      surgery (i.e., transplantation or resection). IR injury, which in most severe
      cases culminates in acute liver failure, is particularly pronounced in livers
      that are affected by non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat
      laden hepatocytes are damaged by chronic oxidative/nitrosative stress (ONS), a
      state that is acutely exacerbated during IR, leading to extensive parenchymal
      damage. RECENT ADVANCES: NAFLD triggers ONS via increased (extra)mitochondrial
      fatty acid oxidation and activation of the unfolded protein response. ONS is
      associated with widespread protein and lipid (per)oxidation, which reduces the
      hepatic antioxidative capacity and shifts the intracellular redox status toward
      an oxidized state. Moreover, activation of the transcription factor peroxisome
      proliferator-activated receptor alpha induces expression of mitochondrial
      uncoupling protein 2, resulting in depletion of cellular energy (ATP) reserves.
      The reduction in intracellular antioxidants and ATP in fatty livers consequently
      gives rise to severe ONS and necrotic cell death during IR. CRITICAL ISSUES:
      Despite the fact that ONS mediates both NAFLD and IR injury, the interplay
      between the two conditions has never been described in detail. An integrative
      overview of the pathophysiology of NAFLD that renders steatotic hepatocytes more
      vulnerable to IR injury is therefore presented in the context of ONS. FUTURE
      DIRECTIONS: Effective methods should be devised to alleviate ONS and the
      consequences thereof in NAFLD before surgery in order to improve resilience of
      fatty livers to IR injury.

PMID- 24294951
TI  - Hepatitis B virus-induced hepatocellular carcinoma: the role of the virus x
      protein.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant diseases and
      has the fourth highest mortality rate worldwide. Chronic hepatitis B virus (HBV)
      infection has been identified as a major risk factor in HCC. Currently available
      evidence support a critical role of hepatitis B virus x (HBx) gene and protein in
      the pathogenesis of HBV-induced HCC. HBx protein is a multifunctional regulator
      that modulates cellular signal transduction pathways, transcriptional
      regulations, cell cycle progress, DNA repair, apoptosis, and genetic stability by
      interacting with different host factors. This review describes the current state
      of knowledge about the biological roles of this protein in the development of
      HCC.

PMID- 24294952
TI  - Mice immunogenicity after vaccination by DNA vaccines containing individual genes
      of a new type of reovirus.
AB  - In this study, we investigated humoral and cellular immune responses in mice to
      DNA vaccines containing individual S or M genes of a new type of reovirus (nRV)
      isolate from a severe acute respiratory syndrome (SARS) patient in Beijing,
      China. Mice were immunized intramuscularly (i.m.) with 100 MUg of S1, S2, S3, S4,
      M1, M2, and M3 DNA vaccine each 4 times in 2-week intervals and assayed for
      humoral IgG, IgG1, IgG2, and IgG2b antibodies by ELISA and for cellular immune
      response, particularly IFN-gamma induction by ELISpot assay. Moreover, CD4+ and
      CD8+ T cell levels in peripheral blood mononuclear cells were assayed by flow
      cytometry. We found that all DNA vaccines induced IgG antibodies, predominantly
      of the IgG2a class and S3 DNA vaccine was the strongest inducer. M2 and S3 DNA
      vaccines elicited Th1- and Th2-based immune responses, respectively, while S1 and
      M3 DNA vaccines induced a mixed Th1/Th2 response. M1, S2, and S4 DNA vaccines
      were poorly immunogenic. To our knowledge, this is the first report
      characterizing mammalian reovirus DNA vaccines applied to a mouse model.

PMID- 24294953
TI  - Characterization of betasatellite associated with the yellow mosaic disease of
      grain legumes in Southern India.
AB  - Yellow mosaic disease caused by mungbean yellow mosaic virus (MYMV) belonging to
      the genus Begomovirus (the family Geminiviridae) is a major constraint in
      cultivation of grain legumes in India. The urdbean (Vigna mungo (L.) Hepper) and
      mungbean (Vigna radiata (L.) R. Wilczek) samples affected with yellow mosaic
      disease exhibits yellow mosaic symptoms along with leaf puckering and leaf
      distortion in Tamil Nadu. Hence the study was performed to find out if there was
      any association and influence of betasatellite DNA on the symptom expression of
      MYMV. Full length viral clones of DNA A and DNA B were obtained through rolling
      circle amplification from YMD infected samples and identified as mungbean yellow
      mosaic virus. Interestingly, betasatellite was found to associate with MYMV, and
      its nucleotide sequence analysis showed its 95% identity with papaya leaf curl
      betasatellite (DQ118862) from cowpea. The present study represents the first
      report about the association of papaya leaf curl betasatellite with MYMV and
      represents a new member of the emerging group of bipartite begomovirus associated
      with betasatellite DNA.

PMID- 24294950
TI  - Extrapelvic endometriosis: a rare entity or an under diagnosed condition?
AB  - Endometriosis is a clinical entity characterized by the presence of normal
      endometrial mucosa abnormally implanted in locations other than the uterine
      cavity. Endometriosis can be either endopelvic or extrapelvic depending on the
      location of endometrial tissue implantation. Despite the rarity of extrapelvic
      endometriosis, several cases of endometriosis of the gastrointestinal tract, the
      urinary tract, the upper and lower respiratory system, the diaphragm, the pleura
      and the pericardium, as well as abdominal scars loci have been reported in the
      literature. There are several theories about the pathogenesis and the
      pathophysiology of endometriosis. Depending on the place of endometrial tissue
      implantation, endometriosis can be expressed with a wide variety of symptoms. The
      diagnosis of this entity is neither easy nor routine. Many diagnostic methods
      clinical and laboratory have been used, but none of them is the golden standard.
      The multipotent localization of endometriosis in combination with the wide range
      of its clinical expression should raise the clinical suspicion in every woman
      with periodic symptoms of extrapelvic organs. Finally, the therapeutic approach
      of this clinical entity is also correlated with the bulk of endometriosis and the
      locum that it is found. It varies from simple observation, to surgical treatment
      and treatment with medication as well as a combination of those. Virtual slides:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1968087883113362.

PMID- 24294954
TI  - Geographic distribution and phylogenetic analysis of cucurbit yellow stunting
      disorder virus in Iran.
AB  - Cucurbit yellow stunting disorder virus (CYSDV) is a destructive virus of
      cucurbits in Iran. During 2008-2012 growing seasons a total of 366 cucurbit
      samples including melon, cucumber, snakemelon and squash with typical symptoms of
      CYSDV infection were collected from ten Provinces in Iran. They were screened by
      ELISA and the infectivity of ELISA-positive samples was confirmed by RT-PCR. The
      results showed that 309 out of 366 samples were infected by CYSDV. The virus was
      present in many areas of southern and central Provinces of the country. Analyses
      of nucleotide and amino acid sequences of the CYSDV coat protein (CP) showed that
      Iranian isolates form a cluster and were placed in the Eastern subgroup of CYSDV.
      The Eastern subgroup of CYSDV was divided into two diverged subgroups including
      Iranian isolates and Saudi Arabian isolates. The identity among Iranian isolates
      was more than 99 %. Estimation of genetic distances showed that the number of
      nucleotide and amino acid substitutions per site from averaging overall Iranian
      sequence pairs were 0.004 and 0.008, respectively. Phylogenetic analyses and the
      estimation of genetic distance indicated that Iranian isolates have low genetic
      diversity.

PMID- 24294955
TI  - Vector-mediated expression of interferon gamma inhibits replication of hepatitis
      B virus in vitro.
AB  - Despite the existence of efficient vaccines against hepatitis B virus (HBV)
      infections, these still represent a serious threat to human health worldwide.
      Acute HBV infections often become chronic, marked by liver cirrhosis and
      hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN
      alpha, gamma) or nucleoside/nucleotide analogs in inhibiting HBV replication in
      vitro have led to therapeutic applications to chronic HBV patients, however,
      their results so far have not been satisfactory. The treatments were either not
      effective in all patients or had adverse effects. Certain progress was expected
      from expression of interferons targeted to liver by adenovirus vectors, however,
      this approach turned out to be limited by undesired expression of toxic viral
      genes and high production costs. Therefore, in this study, we attempted to
      inhibit HBV replication in HepG2.2.15 cells by human IFN-gamma expressed through
      a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN
      gamma, targeted to HBV-replicating cells, significantly inhibited the virus
      growth without inducing apoptosis and indicated that local expression of this
      kind of cytokine may be a promising strategy of gene therapy.

PMID- 24294956
TI  - Expression of bovine Mx1 protein inhibits the replication of foot-and-mouth
      disease virus in BHK-21 cells.
AB  - Mx proteins belonging to the dynamin superfamily of large GTPases inhibit
      replication of a wide range of RNA viruses. In this study, we examined whether
      bovine Mx1 protein could interfere with the replication of foot-and-mouth disease
      virus (FMDV). For this purpose we established cloned BHK-21 cells expressing
      bovine Mx1 protein (BM1 cells) and infected them with FMDV serotype O. Cloned BHK
      21 cells expressing neomycin resistance instead of Mx1 protein (BH1 cells) and
      original BHK-21 cells served as negative controls. The results showed that the
      expression of bovine Mx1 protein reduced viral yields by 90% and levels of viral
      VP1 mRNA by 60%. These findings correlated with a significant reduction of viral
      antigen detectable in infected cells by immunofluorescent assay. These results
      demonstrate that bovine Mx1 protein interferes with the replication of FMDV.

PMID- 24294957
TI  - Multiplex RT-PCR detection and distribution of four apple viruses in China.
AB  - Apple trees are natural hosts of four economically important virus species in
      China. We used a simple, sensitive multiplex RT-PCR protocol with an internal
      control to simultaneously detect and differentiate four apple viruses: apple
      chlorotic leaf spot virus (ACLSV), apple mosaic virus (ApMV), apple stem pitting
      virus (ASPV), and apple stem grooving virus (ASGV). This multiplex RT-PCR could
      be used as an alternative to other routinely used detection methods. We used this
      protocol to evaluate the occurrence and distribution of the four apple viruses in
      China. The four viruses were widely distributed throughout the main apple
      production region of China, including Heilongjiang, Liaoning, Hebei, Beijing,
      Henan, Shanxi, Shaanxi, Shandong, Gansu, Ningxia, Xinjiang, Sichuan, and Yunnan.
      The four viruses, ApMV, ASPV, ASGV, and ACLSV, were present in 80.1%, 65.1%,
      73.7%, and 69.7% of the samples, respectively. Two or more of the viruses were
      detected in most of the infections. The most frequent virus combinations were
      ApMV + ASGV + ASPV + ACLSV with an incidence of 27.22%, followed by ApMV + ASGV +
      ACLSV (14.37%), ApMV + ASGV + ASPV (12.54%), and ASGV + ApMV (11.01%). The
      incidence of the ASPV + ACLSV combination was the lowest (0.61%). This is the
      first extensive survey conducted in China for monitoring the four apple viruses,
      which provides important information for apple virus distribution and management
      in China.

PMID- 24294958
TI  - Expression and functional validation of Bombyx mori nucleopolyhedrovirus ORF29, a
      conserved Nudix motif protein.
AB  - Our previous study showed that Bombyx mori nucleopolyhedrovirus (BmNPV) orf29
      encodes a 26 kDa protein expressed in the early stage of infection cycle. BmNPV
      ORF29, contains a conserved motif of Nudix (nucleotide diphosphate X)
      superfamily. It has the highest homology with ADP-ribose pyrophosphatase
      (ADPRase), a subfamily of Nudix pyrophosphatase. In this work, we purified the
      recombinant BmNPV ORF29 in Escherichia coli by metal chelating affinity
      chromatography. The amino acid sequence of recombinant protein was confirmed by
      mass spectroscopic analysis and found that the purified protein could be able to
      catalyze the breakdown of ADP-ribose to AMP and ribose 5-phosphate, with Km and
      Kcat values of 182 MUmol/l and 5.3 s-1 respectively. The optimal activity was at
      alkaline pH (8.5) with Mg2+ (0.5-mmol/l) ions as the cofactor.

PMID- 24294959
TI  - Disruption of pocket protein dream complexes by E7 proteins of different types of
      human papillomaviruses.
AB  - It has been shown that the E7 protein of the high-risk HPV-16 transforms cells in
      vitro and binds pRB, p107 and p130, so called pocket proteins associated in cells
      with DREAM proteins, while that of the low-risk HPV-6 does not transform cells
      and binds p130 but not pRB or p107. These facts may indicate that p130 is
      essential for the HPV life cycle. To gain further insight into the relationship
      between HPV E7 proteins and pocket protein-DREAM complexes, E7 proteins of HPVs
      of various risk categories were expressed via appropriate vectors in T98G cells
      and the levels of various pocket proteins either total or associated with DREAM
      were analyzed. The obtained results demonstrated that high-risk HPV-16, HPV-18
      and HPV-33, low-risk HPV-1 and HPV-11, and cutaneous HPV-48 disrupted pocket
      protein-DREAM complexes in T98G cells to a similar extent.

PMID- 24294960
TI  - Complete genome sequence of an isolate of papaya leaf distortion mosaic virus
      from commercialized PRSV-resistant transgenic papaya in China.
AB  - Papaya leaf distortion mosaic virus is highly destructive to commercial papaya
      production. Here, the complete genome sequence was determined for an isolate of
      papaya leaf distortion mosaic virus, designated PLDMV-DF, infecting the
      commercialized papaya ringspot virus (PRSV)-resistant transgenic papaya from
      China. Excluding the 3'-poly (A) tail, the sequence shares high sequence identity
      to several PLDMV isolates from Taiwan and Japan and is phylogenetically most
      closely related to the isolate from Japan. Infection of PLDMV-DF in transgenic
      PRSV-resistant papaya may indicate emergence of this disease in genetically
      engineered plants. The reported sequence for this isolate may help generate bi
      transgenic papaya resistant to PRSV and PLDMV.

PMID- 24294961
TI  - Prokaryotic expression and immunoassay of grass carp reovirus capsid VP6 protein.
AB  - Grass carp reovirus (GCRV) of the genus Aquareovirus and the family Reoviridae
      causes a severe hemorrhagic disease in grass carp fingerlings in China. GCRV
      genome is composed of 11 double-stranded RNA segments, of which segment 8 encodes
      the major core capsid protein VP6. In this study, the VP6 gene following an RT
      PCR-amplification from the GCRV 104 strain was cloned into an expression vector
      pET-32a to obtain pET-32(a)-VP6. The VP6 protein was expressed in Escherichia
      coli BL21 as a fusion protein of 64 kDa. After purification with the HisLink Spin
      Protein Purification System the VP6 protein was used to raise a specific
      polyclonal antibody in Balb/c mice. Presence of VP6 protein was proved in
      bacterial lysates containing VP6 fusion protein by Western blot analysis and in
      GCRV-infected CIK cells by immunofluorescent staining using polyclonal antibody.
      These results may be helpful in further studies of interactions between GCRV and
      cells and in preparation of an engineered vaccine against GCRV.

PMID- 24294962
TI  - Histone deacetylase inhibitors suppress coxsackievirus B3 growth in vitro and
      myocarditis induced in mice.
AB  - Clinical importance of myocarditis, predominantly caused by coxsackievirus B3
      (CVB3), is recently rising. However, a detailed mechanism of pathogenesis of CVB3
      myocarditis still needs to be clarified. Recently, it has been reported that
      histone modifications including acetylation are involved in coxsackievirus
      replication. To examine whether the CVB3 replication requires histone
      acetylation, histone deacetylase (HDAC) inhibitors were employed. We found that
      the HDAC2 activity increased in virus-infected cells at 12 hrs p.i. and that HDAC
      inhibitors suppressed the virus replication in vitro. This suggests that the
      HDAC2 activity may be required for the virus replication. Eventually, a HDAC
      inhibitor trichostatin A protected against CVB3-induced myocardial injury in
      vivo. Our results suggest that HDAC may be a novel therapeutic target for
      treating viral myocarditis. KEYWORDS: coxsackievirus B3; histone
      acetyltransferase; histone deacetylase; HDAC inhibitors, trichostatin A;
      apicidin; valproic acid; shRNA; myocarditis; mouse.

PMID- 24294963
TI  - Serological correlates of immune protection conferred by Chikungunya virus
      infection.
AB  - Chikungunya virus (CHIKV), an Alphavirus of the family Togaviridae is a positive
      strand RNA virus that is transmitted commonly by the Aedes mosquitoes. The
      characteristic clinical symptom of the virus infection is incapacitating
      arthralgia that could persist for few weeks to several months in the affected
      individuals (1, 2). High morbidity with severe polyarthralgia, rashes and ocular,
      hemorrhagic and sensorineural complications are reported in the re-emerging
      infection (3-5). The acquisition of an A226V mutation in the envelope protein E1
      has increased the transmissibility of the virus in the widely prevalent Ae.
      Albopictus mosquitoes (6). CHIKV infection has become more widespread in the
      recent years as the mosquito vectors have expanded into new areas. Imported cases
      of CHIKV have been reported in nearly 40 countries until now (7).

PMID- 24294964
TI  - Virus dose-dependent neutrophil and lymphocyte proportions in peripheral blood
      during influenza A infection of mice.

PMID- 24294965
TI  - Increased formation of autophagosomes in ectromelia virus-infected primary
      culture of murine bone marrow-derived macrophages.
AB  - Induction of autophagy by ectromelia virus (ECTV) in primary cultures of bone
      marrow-derived macrophages (BMDMs) was investigated. The results showed that ECTV
      infection of BMDMs resulted in increased formation of autophagosomes, increased
      level of LC3-II protein present in aggregates and extensive cytoplasmic
      vacuolization. These data indicate an increased autophagic activity in BMDMs
      during ECTV infection.

PMID- 24294966
TI  - T regulatory cells in childhood arthritis--novel insights.
AB  - In recent years, there have been many new developments in the field of regulatory
      T cells (Treg), challenging the consensus on their behaviour, classification and
      role(s) in disease. The role Treg might play in autoimmune disease appears to be
      more complex than previously thought. Here, we discuss the current knowledge of
      regulatory T cells through animal and human research and illustrate the recent
      developments in childhood autoimmune arthritis (juvenile idiopathic arthritis
      (JIA)). Furthermore, this review summarises our understanding of the fields and
      assesses current and future implications for Treg in the treatment of JIA. 

PMID- 24294967
TI  - Delta-tocotrienol protects mice from radiation-induced gastrointestinal injury.
AB  - We recently demonstrated that natural delta-tocotrienol (DT3) significantly
      enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone
      marrow cells from radiation-induced damage through Erk activation-associated mTOR
      survival pathways. Here, we further evaluated the effects and mechanisms of DT3
      on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75
      100 mg/kg) or vehicle was administered as a single subcutaneous injection to
      CD2F1 mice 24 h before 10-12 Gy (60)Co total-body irradiation at a dose rate of
      0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum
      sections were stained with hematoxylin and eosin and the surviving crypts in
      irradiated mice were counted. Apoptosis in intestinal epithelial cells was
      measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from
      gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg)
      significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI.
      Administration of DT3 protected intestinal tissue, decreased apoptotic cells in
      jejunum and inhibited gut bacterial translocation in irradiated mice.
      Furthermore, DT3 significantly inhibited radiation-induced production of pro
      inflammatory factors interleukin-1beta and -6 and suppressed expression of
      protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis
      in mouse intestinal cells. Our data demonstrate that administration of DT3
      protected mice from radiation-induced gastrointestinal system damage. 

PMID- 24294968
TI  - Time-resolved fluorescence study of exciplex formation in diastereomeric naproxen
      pyrrolidine dyads.
AB  - The influence of chirality on the elementary processes triggered by excitation of
      the (S,S)- and (R,S)- diastereoisomers of naproxen-pyrrolidine (NPX-Pyr) dyads
      has been studied by time-resolved fluorescence in acetonitrile-benzene mixtures.
      In these systems, the quenching of the (1)NPX*-Pyr singlet excited state occurs
      through electron transfer and exciplex formation. Fluorescence lifetimes and
      quantum yields revealed a significant difference (around 20%) between the (S,S)-
      and (R,S)- diastereomers. In addition, the quantum yields of exciplexes differed
      by a factor of 2 regardless of solvent polarity. This allows us to suggest a
      similar influence of the chiral centers on the local charge transfer resulting in
      exciplex and full charge separation that leads to ion-biradicals. A simplified
      scheme is proposed to estimate a set of rate constant values (k1-k5) for the
      elementary stages in each solvent system. 

PMID- 24294969
TI  - Development of novel dual binders as potent, selective, and orally bioavailable
      tankyrase inhibitors.
AB  - Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase
      (PARP) family. They have been shown to directly bind to axin proteins, which
      negatively regulate the Wnt pathway by promoting beta-catenin degradation.
      Inhibition of tankyrases may offer a novel approach to the treatment of APC
      mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of
      tankyrases through a combination of substructure searching of the Amgen compound
      collection based on a minimal binding pharmacophore hypothesis and high
      throughput screening. Herein we report the structure- and property-based
      optimization of compound 8 leading to the identification of more potent and
      selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties
      in rodents, which are well suited as tool compounds for further in vivo
      validation studies. 

PMID- 24294971
TI  - Boycunts and bonus holes: trans men's bodies, neoliberalism, and the sexual
      productivity of genitals.
AB  - Recent theorizations of trans embodiment have brought attention to the ways
      neoliberalism limits the productivity of nonnormatively gendered bodies. This
      article deals with the discursive framing of embodiment and sexual desirability
      among trans men and other transmasculine persons negotiating Internet-mediated
      homoerotic spaces. Micro-level analysis of discourse structure and macro-level
      analysis of socio-political context together show how trans men navigate
      homonormative sexual economies by linguistically recuperating their bodies'
      sexually productivity. Instead of undermining claims of embodied masculinity and
      homoerotic value, potential sites of exclusion-i.e., trans genitals-become sites
      of flexible accumulation that enhance rather than detract from their bearers'
      desirability.

PMID- 24294970
TI  - Pycup--a bifunctional, cage-like ligand for (64)Cu radiolabeling.
AB  - In developing targeted probes for positron emission tomography (PET) based on
      (64)Cu, stable complexation of the radiometal is key, and a flexible handle for
      bioconjugation is highly advantageous. Here, we present the synthesis and
      characterization of the chelator pycup and four derivatives. Pycup is a cross
      bridged cyclam derivative with a pyridyl donor atom integrated into the cross
      bridge resulting in a pentadentate ligand. The pycup platform provides kinetic
      inertness toward (64)Cu dechelation and offers versatile bioconjugation
      chemistry. We varied the number and type of additional donor atoms by alkylation
      of the remaining two secondary amines, providing three model ligands, pycup2A,
      pycup1A1Bn, and pycup2Bn, in 3-4 synthetic steps from cyclam. All model copper
      complexes displayed very slow decomplexation in 5 M HCl and 90  degrees C (t1/2:
      1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal
      crystal X-ray structure of the [Cu(pycup2Bn)](2+) complex showed that the copper
      was coordinated in a trigonal, bipyramidal manner. The corresponding
      radiochemical complexes were at least 94% stable in rat plasma after 24 h.
      Biodistribution studies conducted in Balb/c mice at 2 h postinjection of (64)Cu
      labeled pycup2A revealed low residual activity in kidney, liver, and blood pool
      with predominantly renal clearance observed. Pycup2A was readily conjugated to a
      fibrin-targeted peptide and labeled with (64)Cu for successful PET imaging of
      arterial thrombosis in a rat model, demonstrating the utility of our new chelator
      in vivo. 

PMID- 24294972
TI  - Objective and subjective components of the first-night effect in young nightmare
      sufferers and healthy participants.
AB  - The first-night effect--marked differences between the first- and the second
      night sleep spent in a laboratory--is a widely known phenomenon that accounts for
      the common practice of excluding the first-night sleep from any polysomnographic
      analysis. The extent to which the first-night effect is present in a participant,
      as well as its duration (1 or more nights), might have diagnostic value and
      should account for different protocols used for distinct patient groups. This
      study investigated the first-night effect on nightmare sufferers (NM; N = 12) and
      healthy controls (N = 15) using both objective (2-night-long polysomnography) and
      subjective (Groningen Sleep Quality Scale for the 2 nights spent in the
      laboratory and 1 regular night spent at home) methods. Differences were found in
      both the objective (sleep efficiency, wakefulness after sleep onset, sleep
      latency, Stage-1 duration, Stage-2 duration, slow-wave sleep duration, and REM
      duration) and subjective (self-rating) variables between the 2 nights and the 2
      groups, with a more pronounced first-night effect in the case of the NM group.
      Furthermore, subjective sleep quality was strongly related to polysomnographic
      variables and did not differ among 1 regular night spent at home and the second
      night spent in the laboratory. The importance of these results is discussed from
      a diagnostic point of view.

PMID- 24294973
TI  - One-pot peptide ligation-desulfurization at glutamate.
AB  - An efficient methodology for ligation at glutamate (Glu) is described. A gamma
      thiol-Glu building block was accessed in only three steps from protected glutamic
      acid and could be incorporated at the N-terminus of peptides. The application of
      these peptides in one-pot ligation-desulfurization chemistry is demonstrated with
      a range of peptide thioesters, and the utility of this methodology is highlighted
      through the synthesis of the osteoporosis peptide drug teriparatide (Forteo). 

PMID- 24294974
TI  - Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus.
AB  - INTRODUCTION: The application of vesicular carrier formulations has generated
      promise of overcoming some problems associated with drug delivery arising from
      not only the physicochemical properties of the drug but also those of the
      biological barriers, such as the membrane linings of various body tissues and the
      skin. This review article discusses the importance of various vesicular carriers,
      namely liposomes, niosomes, transfersomes and ethosomes in drug delivery with
      greater emphasis on ethosomes. AREAS COVERED: The nature, mechanism of drug
      delivery, methods of preparation as well as characterization of vesicular
      carriers was discussed with a focus on ethosomes. An overview of their potential
      applications was provided with discussions on the future prospects and challenges
      of achieving enhanced drug delivery using ethosomes. EXPERT OPINION: Vesicular
      carriers offer controlled and sustained drug release, improved permeability and
      protection of the encapsulated bioactives. Ethosomes offer more efficient and
      enhanced bioavailability better than the older dosage forms owing to the high
      ethanol content. Ethosomes have potential applications in the development of
      nanomedicines, including phytomedicines, for the treatment of challenging
      diseases ravaging the world today. The future holds great prospects in the
      utilization of vesicular carriers, especially ethosomes, in overcoming peculiar
      problems of drug delivery.

PMID- 24294975
TI  - Fabrication of antireflective compound eyes by imprinting.
AB  - In this article, we demonstrate a simple and cost-effective approach to fabricate
      antireflective polymer coatings. The antireflective surfaces have 3D structures
      that mimick moth compound eyes. The fabrication is easily performed via a one
      step imprinting process. The 3D arrays exhibit better antireflective performance
      than 2D arrays over most wavelengths from 400 to 2400 nm. The reflectivity of the
      3D arrays is lower than 5.7% over the all of the wavelengths, and the minimum
      reflectivity is 0.27% at a wavelength of around 1000 nm. 

PMID- 24294976
TI  - EZH2 knockdown suppresses the growth and invasion of human inflammatory breast
      cancer cells.
AB  - INTRODUCTION: Inflammatory breast cancer (IBC) is the most metastatic variant of
      breast cancer with the poorest survival in all types of breast cancer patients
      and presently therapeutic targets for IBC are very limited. Enhancer of zeste
      homolog 2 (EZH2) is frequently expressed in human IBC and its expression
      positively correlates with worse clinical outcome. However, the molecular basis
      for EZH2 promoting IBC has not been explored. Here, we investigated the
      functional role of EZH2 in IBC cells by examining the effects of its knockdown on
      the formation of tumor spheroids and invasion of these cells in vitro and in vivo
      in an orthotopic xenograft model. METHODS: SUM149 and a new IBC cell line-FC-IBC
      02 derived from pleural effusion fluid of an IBC patient were used in this study.
      Specific knockdown of EZH2 was performed using short hairpin RNA (shRNA) specific
      to the human EZH2 gene. Cell growth and the formation of tumor spheroids were
      examined in vitro. The effects of EZH2 knockdown on IBC cell migration and
      invasion were examined by a Boyden chamber assay. For the in vivo tumor growth
      studies, IBC cells were orthotopically transplanted into the mammary fat pads of
      immunodeficient mice. RESULTS: The results showed that EZH2 is expressed at
      higher levels in human IBC cell lines compared with normal human mammary
      epithelial cells, and the knockdown of EZH2 expression significantly suppressed
      cell growth and tumor spheroid formation of human IBC cells in vitro. In
      addition, EZH2 knockdown inhibited the migration and invasion of IBC cells.
      Significantly, EZH2 knockdown suppressed the angiogenesis and tumor growth of IBC
      cells in vivo. CONCLUSIONS: Our results provide direct evidence that EZH2 is
      critical for the formation of tumor spheroids and invasion of human IBC cells and
      could be a potential target for developing novel therapeutic strategies for human
      IBC.

PMID- 24294977
TI  - The new nordic diet--consumer expenditures and economic incentives estimated from
      a controlled intervention.
AB  - BACKGROUND: Several studies suggest that a healthy diet with high emphasis on
      nutritious, low-energy components such as fruits, vegetables, and seafood tends
      to be more costly for consumers. Derived from the ideas from the New Nordic
      Cuisine--and inspired by the Mediterranean diet, the New Nordic Diet (NND) has
      been developed as a palatable, healthy and sustainable diet based on products
      from the Nordic region. The objective of the study is to investigate economic
      consequences for the consumers of the NND, compared with an Average Danish Diet
      (ADD). METHODS: Combine quantity data from a randomized controlled ad libitum
      dietary 6 month intervention for central obese adults (18-65 years) and market
      retail price data of the products consumed in the intervention. Adjust consumed
      quantities to market price incentives using econometrically estimated price
      elasticities. RESULTS: Average daily food expenditure of the ADD as represented
      in the unadjusted intervention (ADD-i) amounted to 36.02 DKK for the
      participants. The daily food expenditure in the unadjusted New Nordic Diet (NND
      i) costs 44.80 DKK per day per head, and is hence about 25% more expensive than
      the Average Danish Diet (or about 17% when adjusting for energy content of the
      diet). Adjusting for price incentives in a real market setting, the estimated
      cost of the Average Danish Diet is reduced by 2.50 DKK (ADD-m), compared to the
      unadjusted ADD-i diet, whereas the adjusted cost of the New Nordic Diet (NND-m)
      is reduced by about 3.50 DKK, compared to the unadjusted NND-i. The distribution
      of food cost is however much more heterogeneous among consumers within the NND
      than within the ADD. CONCLUSION: On average, the New Nordic Diet is 24-25 per
      cent more expensive than an Average Danish Diet at the current market prices in
      Denmark (and 16-17 per cent, when adjusting for energy content). The relatively
      large heterogeneity in food costs in the NND suggests that it is possible to
      compose an NND where the cost exceeds that of ADD by less than the 24-25 per
      cent.

PMID- 24294980
TI  - Presence of mycotoxins in sorghum and intake estimation in Tunisia.
AB  - Sorghum samples (n = 60) from Tunisian markets were analysed for the occurrence
      of 22 of both traditional and emerging mycotoxins. Samples were extracted with a
      QuEChERS-like method and mycotoxins were detected by LC-MS/MS. This method was
      validated and adequate analytical parameters were obtained. All samples had
      contamination with mycotoxins and several samples had higher contamination levels
      than European Union legislative limits (MLs). The most frequently found
      mycotoxins were ENB (100%), OTA (98%), ENA1 (63%), ENB1 (56%), BEA (48%), AFB1
      (38%) and STG (33%). Mean contaminations were 30.7, 1.93, 33.2, 51.0, 15.4, 1.49
      and 20.5 ug kg(-1), respectively. While two samples were contaminated with FB2
      and FB3 at mean values of 16.2 and 45.9 ug kg(-1), respectively, one sample was
      contaminated with AFB2 and ZEA at levels of 0.82 and 45.0 ug kg(-1),
      respectively. The results were used to estimate the daily intake of mycotoxins
      through sorghum consumption with regard to normal consumers (low-risk population)
      and high consumers such as babies (high-risk consumers) who are facing an
      alarming situation.

PMID- 24294978
TI  - NADPH oxidase 1, a novel molecular source of ROS in hippocampal neuronal death in
      vascular dementia.
AB  - AIMS: Chronic cerebral hypoperfusion (CCH) is a common pathological factor that
      contributes to neurodegenerative diseases such as vascular dementia (VaD).
      Although oxidative stress has been strongly implicated in the pathogenesis of
      VaD, the molecular mechanism underlying the selective vulnerability of
      hippocampal neurons to oxidative damage remains unknown. We assessed whether the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, a
      specialized superoxide generation system, plays a role in VaD by permanent
      ligation of bilateral common carotid arteries in rats. RESULTS: Male Wistar rats
      (10 weeks of age) were subjected to bilateral occlusion of the common carotid
      arteries (two-vessel occlusion [2VO]). Nox1 expression gradually increased in
      hippocampal neurons, starting at 1 week after 2VO and for approximately 15 weeks
      after 2VO. The levels of superoxide, DNA oxidation, and neuronal death in the CA1
      subfield of the hippocampus, as well as consequential cognitive impairment, were
      increased in 2VO rats. Both inhibition of Nox by apocynin, a putative Nox
      inhibitor, and adeno-associated virus-mediated Nox1 knockdown significantly
      reduced 2VO-induced reactive oxygen species generation, oxidative DNA damage,
      hippocampal neuronal degeneration, and cognitive impairment. INNOVATION AND
      CONCLUSION: We provided evidence that neuronal Nox1 is activated in the
      hippocampus under CCH, causing oxidative stress and consequential hippocampal
      neuronal death and cognitive impairment. This evidence implies that Nox1-mediated
      oxidative stress plays an important role in neuronal cell death and cognitive
      dysfunction in VaD. Nox1 may serve as a potential therapeutic target for VaD.

PMID- 24294979
TI  - Dynamic measurements of membrane insertion potential of synthetic cell
      penetrating peptides.
AB  - Cell penetrating peptides (CPPs) have been established as excellent candidates
      for mediating drug delivery into cells. When designing synthetic CPPs for drug
      delivery applications, it is important to understand their ability to penetrate
      the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers
      at the air-water interface are used as model cell membranes to monitor the
      membrane insertion potential of synthetic CPPs. The insertion potential of CPPs
      having different cationic and hydrophobic amino acids were recorded using a
      Langmuir monolayer approach that records peptide adsorption to model membranes.
      Fluorescence microscopy was used to visualize alterations in phospholipid packing
      due to peptide insertion. All CPPs had the highest penetration potential in the
      presence of anionic phospholipids. In addition, two of three amphiphilic CPPs
      inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did.
      All the CPPs studied induced disruptions in phospholipid packing and domain
      morphology, which were most pronounced for amphiphilic CPPs. Overall, small
      changes to amino acids and peptide sequences resulted in dramatically different
      insertion potentials and membrane reorganization. Designers of synthetic CPPs for
      efficient intracellular drug delivery should consider small nuances in CPP
      electrostatic and hydrophobic properties. 

PMID- 24294981
TI  - Liposomal codelivery of a synergistic combination of bioactive lipids in the
      treatment of acute myeloid leukemia.
AB  - AIM: The aim of this work was to develop a liposomal formulation to facilitate
      delivery of a synergistic safingol/C2-ceramide combination in the treatment of
      acute myeloid leukemia (AML). MATERIALS & METHODS: Liposomes were prepared using
      the extrusion method and the bioactive lipids were encapsulated passively. Drug
      concentrations were determined by liquid chromatography tandem mass spectrometry.
      Antileukemic activity was evaluated using human leukemic cell lines, patient
      samples and U937 leukemic xenograft models. RESULTS: A stable liposome
      formulation was developed to coencapsulate safingol and C2-ceramide at 1:1 molar
      ratio with >90% encapsulation efficiency. The liposomal safingol/C2-ceramide was
      effective in AML cell lines, patient samples and murine xenograft models of AML,
      compared with liposomal safingol or liposomal C2-ceramide alone despite a dose
      reduction of 33%. CONCLUSION: Our study provided proof-of-concept evidence to
      deliver synergistic combination of bioactive lipid to achieve complete remission
      in AML.

PMID- 24294982
TI  - PEG-PCL-DEX polymersome-protamine vector as an efficient gene delivery system via
      PEG-guided self-assembly.
AB  - AIM: The nonviral carrier system based on the triblock copolymer PEG-PCL-DEX
      (PPD) and protamine was developed for nucleic acid delivery. MATERIALS & METHODS:
      Self-assembly occurred in the PEG continuous phase to form 'dextran-interior'
      polymersomes. siRNA can be condensed by protamine and encapsulated into PPD
      polymersomes in order to form the PPD-protamine siRNA nanoparticles by
      thermodynamically preferential partition between the PEG continuous phase and the
      dextran cavity. RESULTS: This system can package siRNA into PPD polymersomes to
      form 145.2 +/- 8.02-nm (+/- standard deviation) nanoparticles, and the zeta
      potential can be reduced to approximately 0 mV. PPD-protamine siRNA nanoparticles
      achieved cellular uptake of siRNA in SMMC-7721 cells with negligible
      cytotoxicity, and the GL3 gene expression can be reduced to 61.73 +/- 6.25%. A
      biodistribution study of nanoparticles suggested that the PPD-protamine siRNA
      nanoparticles mainly accumulated in liver. CONCLUSION: All of these results
      suggest that PPD-protamine carriers may offer a promising gene delivery strategy
      for the treatment of liver-related disease.

PMID- 24294983
TI  - Facile preparation of well-defined hydrophilic core-shell upconversion
      nanoparticles for selective cell membrane glycan labeling and cancer cell
      imaging.
AB  - Molecular imaging enables in situ visualization of biomolecules in living
      organisms and creates numerous opportunities for basic biological research and
      early disease diagnosis. As luminescent probes for molecular imaging, lanthanide
      doped upconversion nanoparticles (UCNPs) exhibit superior performance compared to
      conventional fluorescent dyes in many ways, including high tissue penetration
      depth and minimized autofluorescence and photobleaching, making them particularly
      advantageous for imaging analysis. Although various synthesis methods have been
      reported, the preparation of high quality, water-soluble UCNPs remains
      challenging. For in situ imaging, glycans on the cell surface are particularly
      attractive due to their key roles in cellular activity and disease occurrence and
      development. However, glycan imaging is a challenging task due to their diverse
      structures and incompatibility with genetically encoded fluorescent tagging
      techniques. Herein, we report a new type of highly water-soluble, lectin
      functionalized core-shell UCNP synthesized by surface-initiated atom transfer
      radical polymerization (SI-ATRP) for selective cell membrane glycan labeling and
      cancer cell imaging. SI-ATRP modification results in controlled growth of
      hydrophilic polymers on the UCNP surface and well-defined core-shell structure,
      producing UCNPs with improved biocompatibility and intact luminance property.
      Furthermore, the numerous functional groups on the polymer brush shell provide a
      large number of binding sites and 3D support for lectin immobilization. The
      increased loading density and diversified architecture of the immobilized lectins
      facilitates multivalent binding between the lectins and the glycans on the cell
      surface and leads to selective labeling of highly metastatic hepatocellular
      carcinoma cells (HCCHM3) in vitro and successful in vivo imaging of HCCHM3
      inoculated mice. 

PMID- 24294985
TI  - Medicinal chemistry of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1).
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme primarily
      responsible for the regulation of intracellular cortisol levels. Inhibition of
      11beta-HSD1 is an attractive mechanism for the treatment of obesity and other
      elements of the metabolic syndrome. Emerging literature also supports a potential
      role in the treatment of other unmet medical needs including Alzheimer's disease,
      vascular inflammation, cardiovascular disease, and glaucoma. The aim of this
      article is to review the medicinal chemistry literature around small molecule
      approaches to developing synthetic inhibitors of 11beta-HSD1 and to highlight key
      compounds that have resulted from the efforts of both industrial and academic
      groups. The reported data from 11beta-HSD1 inhibitors that have progressed into
      the clinic are summarized followed by a perspective from the authors. 

PMID- 24294984
TI  - Parent-child relationships in Type 1 diabetes: associations among child behavior,
      parenting behavior, and pediatric parenting stress.
AB  - Interactions between parents and children can influence behavioral and emotional
      functioning related to Type 1 diabetes (T1D), yet have been relatively unexplored
      during preadolescence. The present study examined associations among child
      problem behaviors, critical parenting behaviors, and pediatric parenting stress
      in a sample of preadolescent youth with T1D. Data are available from 86
      preadolescent-parent dyads who participated in the initial baseline assessment of
      a randomized controlled trial designed to assess the efficacy of an adherence
      promotion program. Measures included the Eyberg Child Behavior Inventory, the
      Diabetes Family Behavior Checklist, and the Pediatric Inventory for Parents.
      After controlling for significant demographic and medical characteristics,
      parents who reported their child's behavior as more problematic reported more
      difficulty with pediatric parenting stress, which was also associated with more
      child-reported critical parenting behaviors. Child problem behaviors and critical
      parenting behaviors were associated with one another, partially via their
      association with increased pediatric parenting stress. Potential clinical
      applications include interventions geared toward helping parents manage difficult
      child behaviors as well as cope with pediatric parenting stress, with the
      ultimate goal of improving the parent-child relationship and management of T1D.

PMID- 24294987
TI  - Mood-congruent false memories persist over time.
AB  - In this study, we examined the role of mood-congruency and retention interval on
      the false recognition of emotion laden items using the Deese/Roediger-McDermott
      (DRM) paradigm. Previous research has shown a mood-congruent false memory
      enhancement during immediate recognition tasks. The present study examined the
      persistence of this effect following a one-week delay. Participants were placed
      in a negative or neutral mood, presented with negative-emotion and neutral
      emotion DRM word lists, and administered with both immediate and delayed
      recognition tests. Results showed that a negative mood state increased remember
      judgments for negative-emotion critical lures, in comparison to neutral-emotion
      critical lures, on both immediate and delayed testing. These findings are
      discussed in relation to theories of spreading activation and emotion-enhanced
      memory, with consideration of the applied forensic implications of such findings.

PMID- 24294986
TI  - Listening to the rumours: what the northern Nigeria polio vaccine boycott can
      tell us ten years on.
AB  - In 2003 five northern Nigerian states boycotted the oral polio vaccine due to
      fears that it was unsafe. Though the international responses have been
      scrutinised in the literature, this paper argues that lessons still need to be
      learnt from the boycott: that the origins and continuation of the boycott were
      due to specific local factors. We focus mainly on Kano state, which initiated the
      boycotts and continued to reject immunisations for the longest period, to provide
      a focused analysis of the internal dynamics and complex multifaceted causes of
      the boycott. We argue that the delay in resolving the year-long boycott was
      largely due to the spread of rumours at local levels, which were intensified by
      the outspoken involvement of high-profile individuals whose views were
      misunderstood or underestimated. We use sociological concepts to analyse why
      these men gained influence amongst northern Nigerian communities. This study has
      implications on contemporary policy: refusals still challenge the Global Polio
      Eradication Initiative; and polio remains endemic to Nigeria (Nigeria accounted
      for over half of global cases in 2012). This paper sheds light on how this
      problem may be tackled with the ultimate aim of vaccinating more children and
      eradicating polio. 

PMID- 24294988
TI  - Body mass index and labour outcome in Egyptian women.
AB  - We conducted a cross-sectional descriptive study to evaluate the impact of body
      mass index (BMI) on maternal medical disorders, progress of labour, mode of
      delivery and neonatal outcome in Cairo University hospital between September 2012
      and March 2013. A total of 574 parturients were divided into two groups: group A
      with a BMI < 30 and group B with a BMI >= 30. A statistically significant
      difference was found in favour of group B, regarding medical disorders,
      especially gestational hypertension and pre- eclampsia (p < 0.001), caesarean
      deliveries (p < 0.001) and neonatal birth weight (p = 0.001). There was no
      difference regarding gestational age at delivery, progress of labour (cervical
      dilatation, cervical effacement, duration of first and second stage of labour)
      and neonatal outcome (Apgar score at 1 and 5 min and neonatal deaths). Our
      conclusion is that increased maternal BMI is associated with an increased
      incidence of medical disorders during pregnancy, caesarean section rate and fatal
      macrosomia.

PMID- 24294989
TI  - Evidence base updates: the evolution of the evaluation of psychological
      treatments for children and adolescents.
AB  - This article introduces a new feature in the journal: Evidence Base Updates.
      Starting with this issue of the journal, there will be one such update in each
      issue. The updates will focus on reviewing the treatments studies focused on a
      specific child/adolescent problem area and identifying those treatments with the
      strongest evidence base. Updates will use a revised set of criteria for
      evaluating the evidence, based on past work, but modified to emphasize
      methodological rigor of studies and designed to identify those treatments with
      questionable efficacy. The article also places the evaluation of psychological
      treatments in historical context. As well, the changes made in the criteria are
      discussed. 

PMID- 24294990
TI  - Primary solitary fibrous tumors of liver: a case report and literature review.
AB  - A 42-year-old male presented right upper abdomen pain for more than 6 days, which
      misdiagnose calculus of intrahepatic duct and acute cholecystitis. An
      approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left
      lateral lobe of hepatic. Pathological examination showed spindle cell and
      fibroblast -like cells within the collagenous stroma. Immunohistochemically,
      these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S
      100 protein and HMB45 were negative. The post-operative course was uneventful.
      Solitary fibrous tumors of the liver, although rare, should be differentiated
      from mesenchymal lesions of the liver. Virtual slide: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088.

PMID- 24294991
TI  - Cell-specific and pH-activatable rubyrin-loaded nanoparticles for highly
      selective near-infrared photodynamic therapy against cancer.
AB  - Spatiotemporal control of singlet oxygen ((1)O2) release is a major challenge for
      photodynamic therapy (PDT) against cancer with high therapeutic efficacy and
      minimum side effects. Here a selenium-rubyrin (NMe2Se4N2)-loaded nanoparticle
      functionalized with folate (FA) was designed and synthesized as an acidic pH
      activatable targeted photosensitizer. The nanoparticles could specifically
      recognize cancer cells via the FA-FA receptor binding and were selectively taken
      up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which
      NMe2Se4N2 was activated to produce (1)O2. The pH-controllable release of (1)O2
      specially damaged the lysosomes and thus killed cancer cells in a lysosome
      associated pathway. The introduction of selenium into the rubyrin core enhanced
      the (1)O2 generation efficiency due to the heavy atom effect, and the
      substitution of dimethylaminophenyl moiety at meso-position led to the pH
      controllable activation of NMe2Se4N2. Under near-infrared (NIR) irradiation,
      NMe2Se4N2 possessed high singlet oxygen quantum yield (PhiDelta) at an acidic pH
      (PhiDelta = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological
      pH (PhiDelta = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH
      activatable photosensitization at NIR region and the cancer cell-targeting
      feature led to excellent capability to selectively kill cancer cells and prevent
      the damage to normal cells, which greatly lowered the side effects. Through
      intravenous injection of FA-NMe2Se4N2 nanoparticles in tumor-bearing mice, tumor
      elimination was observed after NIR irradiation. This work presents a new paradigm
      for specific PDT against cancer and provides a new avenue for preparation of
      highly efficient photosensitizers. 

PMID- 24294992
TI  - Derivative plumbing: redesigning washrooms, bodies, and trans affects in ds+r's
      Brasserie.
AB  - diller scofidio + renfro's Brasserie restaurant sets the scene for this article's
      overarching question: what are the stakes of absorbing "the washroom" into our
      affective habits as trans people? This article uses architectural theory to show
      that some hygienic models of transgender-such as "original plumbing"-are less
      about explaining our genders to ourselves and more about (1) communicating our
      "fuckability" to (presumably non-trans) others and (2) codifying subtle and often
      problematic beliefs about the relationship between architecture and the body.

PMID- 24294993
TI  - Uniform, homogenous coatings of carbon nanohorns on arbitrary substrates from
      common solvents.
AB  - We demonstrate a facile technique to electrophoretically deposit homogenous
      assemblies of single-walled carbon nanohorns (CNHs) from common solvents such as
      acetone and water onto nearly any substrate including insulators, dielectrics,
      and three-dimensional metal foams, in many cases without the aid of surfactants.
      This enables the generation of pristine film-coatings formed on time scales as
      short as a few seconds and on three-dimensional templates that enable the
      formation of freestanding polymer-CNH supported materials. As electrophoretic
      deposition is usually only practical on conductive electrodes, we emphasize our
      observation of efficient deposition on nearly any material, including
      nonconductive substrates. The one-step versatility of deposition on these
      materials provides the capability to directly assemble CNH materials onto
      functional surfaces for a broad range of applications. In this manner, we
      utilized as-deposited CNH films as conductometric gas sensors exhibiting better
      sensitivity in comparison to equivalent single-walled carbon nanotube sensors.
      This gives a route toward scalable and inexpensive solution-based processing
      routes to manufacture functional nanocarbon materials for catalysis, energy, and
      sensing applications, among others. 

PMID- 24294994
TI  - Facilitating HIV status disclosure for pregnant women and partners in rural
      Kenya: a qualitative study.
AB  - BACKGROUND: Women's ability to safely disclose their HIV-positive status to male
      partners is essential for uptake and continued use of prevention of mother-to
      child transmission (PMTCT) services. However, little is known about the
      acceptability of potential approaches for facilitating partner disclosure. To lay
      the groundwork for developing an intervention, we conducted formative qualitative
      research to elicit feedback on three approaches for safe HIV disclosure for
      pregnant women and male partners in rural Kenya. METHODS: This qualitative
      acceptability research included in-depth interviews with HIV-infected pregnant
      women (n = 20) and male partners of HIV-infected women (n = 20) as well as two
      focus groups with service providers (n = 16). The participants were recruited at
      health care facilities in two communities in rural Nyanza Province, Kenya, during
      the period June to November 2011. Data were managed in NVivo 9 and analyzed using
      a framework approach, drawing on grounded theory. RESULTS: We found that
      facilitating HIV disclosure is acceptable in this context, but that individual
      participants have varying expectations depending on their personal situation.
      Many participants displayed a strong preference for couples HIV counseling and
      testing (CHCT) with mutual disclosure facilitated by a trained health worker.
      Home-based approaches and programs in which pregnant women are asked to bring
      their partners to the healthcare facility were equally favored. Participants felt
      that home-based CHCT would be acceptable for this rural setting, but special
      attention must be paid to how this service is introduced in the community,
      training of the health workers who will conduct the home visits, and
      confidentiality. CONCLUSION: Pregnant couples should be given different options
      for assistance with HIV disclosure. Home-based CHCT could serve as an acceptable
      method to assist women and men with safe disclosure of HIV status. These findings
      can inform the design and implementation of programs geared at promoting HIV
      disclosure among pregnant women and partners, especially in the home-setting.

PMID- 24294995
TI  - Latent cytokines for targeted therapy of inflammatory disorders.
AB  - INTRODUCTION: The use of cytokines as therapeutic agents is important, given
      their potent biological effects. However, this very potency, coupled with the
      pleiotropic nature and short half-life of these molecules, has limited their
      therapeutic use. Strategies to increase the half-life and to decrease toxicity
      are necessary to allow effective treatment with these molecules. AREAS COVERED: A
      number of strategies are used to overcome the natural limitations of cytokines,
      including PEGylation, encapsulation in liposomes, fusion to targeting peptides or
      antibodies and latent cytokines. Latent cytokines are engineered using the
      latency-associated peptide of transforming growth factor-beta to produce
      therapeutic cytokines/peptides that are released only at the site of disease by
      cleavage with disease-induced matrix metalloproteinases. The principles
      underlying the latent cytokine technology are described and are compared to other
      methods of cytokine delivery. The potential of this technology for developing
      novel therapeutic strategies for the treatment of diseases with an inflammatory
      mediated component is discussed. EXPERT OPINION: Methods of therapeutic cytokine
      delivery are addressed. The latent cytokine technology holds significant
      advantages over other methods of drug delivery by providing simultaneously
      increased half-life and localised drug delivery without systemic effects.
      Cytokines that failed clinical trials should be reassessed using this delivery
      system.

PMID- 24294996
TI  - Structure and electronic spectra of purine-methyl viologen charge transfer
      complexes.
AB  - The structure and properties of the electron donor-acceptor complexes formed
      between methyl viologen and purine nucleosides and nucleotides in water and the
      solid state have been investigated using a combination of experimental and
      theoretical methods. Solution studies were performed using UV-vis and (1)H NMR
      spectroscopy. Theoretical calculations were performed within the framework of
      density functional theory (DFT). Energy decomposition analysis indicates that
      dispersion and induction (charge-transfer) interactions dominate the total
      binding energy, whereas electrostatic interactions are largely repulsive. The
      appearance of charge transfer bands in the absorption spectra of the complexes
      are well-described by time-dependent DFT and are further explained in terms of
      the redox properties of purine monomers and solvation effects. Crystal structures
      are reported for complexes of methyl viologen with the purines 2'-deoxyguanosine
      3'-monophosphate (DAD'DAD' type) and 7-deazaguanosine (DAD'ADAD' type).
      Comparison of the structures determined in the solid state and by theoretical
      methods in solution provides valuable insights into the nature of charge-transfer
      interactions involving purine bases as electron donors. 

PMID- 24294997
TI  - Inflammatory diarrhea due to enteroaggregative Escherichia coli: evidence from
      clinical and mice model studies.
AB  - BACKGROUND: This study was conducted to determine the role of enteroaggregative
      Escherichia coli (EAEC) in inflammatory diarrhea among hospitalized patients in
      Kolkata. The inflammatory pathogenesis of EAEC was established in mice model and
      histopathological studies. Presence of fecal leucocytes (FLCs) can be suspected
      for EAEC infection solely or as a mixed with other enteric pathogens. METHODS:
      Active surveillance was conducted for 2 years on 2 random days per week with
      every 5th patient admitted to the Infectious Diseases Hospital (IDH). Diarrheal
      samples were processed by conventional culture, microscopy, ELISA and molecular
      methods. Two EAEC isolated as sole pathogens were examined in mice after induced
      intestinal infection. The intestinal tissue samples were processed to analyze the
      histological changes. RESULTS: Of the 2519 samples screened, fecal leucocytes,
      erythrocytes and occult blood were detected in 1629 samples. Most of the patients
      had acute watery diarrhea (75%) and vomiting (78%). Vibrio cholerae O1 was the
      main pathogen in patients of 5-10 years age group (33%). Shigellosis was more in
      children from 2-5 years of age (19%), whereas children <2 years appeared to be
      susceptible for infection caused by EAEC (16%). When tested for the
      pathogenicity, the EAEC strains colonized well and caused inflammatory infection
      in the gut mucosa of BALB/C mice. CONCLUSION: This hospital-based surveillance
      revealed prevalence of large number of inflammatory diarrhea. EAEC was the
      suspected pathogen and <2 years children appeared to be the most susceptible age
      group. BALB/C mice may be a suitable animal model to study the EAEC-mediated
      pathogenesis.

PMID- 24294998
TI  - Comparative study of the use of sarcosine, proline and glycine as acrylamide
      inhibitors in ripe olive processing.
AB  - The main purpose of this study was to evaluate the inhibitory effect on
      acrylamide (AA) formation and the impact on sensory characteristics in ripe
      olives of three selected amino acids (sarcosine, proline and glycine), which
      previously showed high AA inhibition rates in an olive model system. Each amino
      acid was separately added to packing solutions to give 100 or 200 mM at
      equilibrium, prior to a sterilisation treatment at 121 degrees C. The results
      showed that sarcosine at 100 mM may be a good candidate for reducing the AA
      content in ripe olives with a limited effect on sensory characteristics. Studies
      with a model solution of AA and sarcosine heated at 121 degrees C for 30 min
      suggested that the main mechanism for the inhibitory effect of sarcosine on AA
      formation was the Michael reaction.

PMID- 24294999
TI  - Evaluation of cephalometric, hormonal and enzymatic parameters in young obese
      subjects.
AB  - AIM: The aim of the present investigation was to analyse cephalometric skeletal
      structures and hormonal and enzymatic parameters in young obese subjects in
      comparison with those of normal weight subjects. MATERIALS AND METHODS: The whole
      sample consisted of 50 Caucasian patients (28 males and 22 females) whose lateral
      radiographs, laboratory hormonal and enzymatic analyses were already available.
      The test group included 25 obese patients (11 females and 14 males, average age:
      9.8 +/- 2.11 years old), while the control group included 25 normal weight
      subjects matched for age and sex (11 females and 14 males, 9.9 +/- 2.5 years
      old). Data were statistically analysed: Student's t-test for independent samples
      was adopted and the level of significance was set at: p < 0.05. RESULTS: As
      regards cephalometric records, the anterior cranial base length was significantly
      greater in the test group (S-N: 69.9 +/- 4 mm) compared to the controls (S-N:
      68.1 +/-2.7 mm). Moreover, the maxillary lenght was higher in the test group (Pm
      A: 48.5 +/- 2.5 mm) in comparison to the control group (Pm-A: 46.1 +/- 1.9 mm).
      As regards skeletal class and vertical dimension, no significant differences were
      found between the two groups, with the exception of the intermaxillary plane
      angle, which was significantly lower in the obese subjects in comparison to the
      controls. Laboratory analysis showed significant (p < 0.05) higher levels of
      leptin and insulin in the test group in comparison with control subjects.
      Furthermore, LH, FSH, IGF-1 values were significantly (p < 0.05) lower in the
      test group in comparison with the control group. CONCLUSION: Obese subjects
      exhibited an increase of some craniofacial parameters and alteration of some
      laboratory parameters that may be involved in the process of skeletal maturation,
      in comparison to normal weight subjects. These findings may be of interest in
      orthodontics, as young obese subjects may need a different orthodontic treatment
      plan in comparison to normal weight subjects of the same age.

PMID- 24295000
TI  - Association between obesity and periodontal disease in children.
AB  - AIM: The objective of this study was to analyse the relationship between obesity
      and periodontal disease in children. The null hypothesis is that obese and normal
      weight children show no different degree of periodontal status. MATERIALS AND
      METHODS: The sample for this case control study consisted of 20 males and 24
      females with a mean age of 9.43+/-2.05 years old and mean body mass index
      standard deviation score (BMI-SDS) of 2.16+/-0.37 in the test group, and 33 males
      and 26 females with a mean age of 9.67+/-1.46 years old and BMI-SDS of 0.22+/
      1.79 in the control group. The periodontal status was assessed using plaque
      accumulation, bleeding on probing (BOP) index, probing depth (PD) and clinical
      attachment level (CAL). RESULTS: The test group showed higher plaque deposits and
      BOP and the difference between the two groups was statistically significant (p<
      0.05). No significant difference between the two groups was found regarding the
      loss of clinical attachment, though it was worse in obese children. Categorical
      variables described as frequency and percentage were compared using the Fisher's
      exact test or test chi square. Continuous variables were analysed using the Mann
      Whitney test. CONCLUSION: The study showed an association between obesity and
      periodontal risk indicators in children that in the long term may lead to oral
      conditions. The oral health of overweight/obese subjects should be more carefully
      supervised and checked in order to prevent oral alterations.

PMID- 24295001
TI  - Association between dental caries and obesity in preschool children.
AB  - AIM: The purpose of this study was to investigate the association between dental
      caries and obesity in preschool children. MATERIALS AND METHODS: A total of 329
      preschool children were recruited from nine day care centers. A qualified dentist
      examined the oral health of each child and a caries score was recorded.
      Anthropometric measurements included body weight, height, triceps skinfold
      thickness, and body fat. Body mass index, and weight-for-height index were
      calculated. Parents or guardians answered a questionnaire regarding their
      children's dietary patterns, oral hygiene habits, and medical history, as well as
      parental practices and attitudes towards their children's oral health. RESULTS:
      The prevalence of dental caries was 73% in this study. Fourteen percent of the
      children were overweight or obese. The caries scores were not significantly
      different according to weight-for-height index categories. After taking into
      account important factors in the multiple regression models, body mass index and
      weight-for-height index, respectively, were not significantly associated with
      dental caries. CONCLUSION: This study showed that obesity was not significantly
      associated with dental caries in preschool children.

PMID- 24295002
TI  - Respiratory disorders in paediatric age: orthodontic diagnosis and treatment in
      dysmetabolic obese children and allergic slim children.
AB  - AIM: Obesity and allergic susceptibility are worsening problems in the most
      industrialised countries. With different mechanisms, they both lead to a
      deterioration of children's life quality because they affect the respiratory
      system, leading to asthma and respiratory disorders such as mouth breathing and
      obstructive sleep apnoea. The latter are related to specific types of
      malocclusions that require an early diagnosis and specific multidisciplinary
      treatment. The purpose of this work is to show the characteristic signs and
      symptoms of these disorders in children of the two phenotypes (allergic and slim,
      obese and dysmetabolic). Intercepting such issues allows both pediatricians and
      paediatric dentists to refer the child to a multidisciplinary team of specialists
      able to deal, in a holistic way, with both the physical and behavioural causes,
      and also with the consequences on systemic and craniofacial development in
      particular. MATERIALS AND METHODS: The literature available on this topic in the
      years between 1997 and 2011 was reviewed, paying special attention to prevention,
      paediatric visits, diagnostic tools and treatment options for each of the two
      conditions. CONCLUSION: Dysmetabolic obese children and allergic slim children
      have specific respiratory problems during rest and exercise. Mouth breathing and
      obstructive sleep apnoea are due to an abnormal craniofacial development and can
      cause serious systemic problems in adulthood. Intercepting early signs of
      pathognomonic symptoms of sleep aponea and mouth breathing permits to treat
      children with an early multidisciplinary approach, and allows for proper physical
      and psychological development of the child.

PMID- 24295003
TI  - Differences in craniofacial characteristics in Southern Italian children from
      Naples: a retrospective study by cephalometric analysis.
AB  - AIM: The present cross-sectional survey was performed to determine cephalometric
      standards in a large sample (n. 1071) of children from Southern Italy (Naples).
      MATERIALS AND METHODS: 1071 lateral cephalograms of healthy children, between 8
      to 12 years, with various types of occlusion, all with no history of orthodontic
      treatment before cephalometric analysis were examined. Seven angular and three
      linear length measurements (SNA, SNB, ANB, SN^GoMe, PN^Pal I^SN, i^GoMe), and
      three ratios were included. Descriptive statistics, including the mean, standard
      deviation, and maximum and minimum, values was computed for each cephalometric
      variable. RESULTS: Changes in angular and linear parameters during the
      observation period occurred mostly between the ages of 10 and 12 years. The three
      ratios varied from age and were not characterised by a progressive rise in mean
      values. Se-N/Go-Pg was greater in 11-year-old boys (p <0.05) and 12-year-old boys
      (p <0.01); the cranio-maxillary index Se-N/PNS-A1 was greater in 9-year-old girls
      (p <0.05), whereas the maxilla-mandibular index PNS-A1/Go-Pg was greater in 9
      year-old boys (p <0.01). CONCLUSION: The findings provided useful reference
      cephalometric normative measures for the 8-to-12-year-old Southern Italian
      children population. Significant differences between boys and girls in the length
      of the anterior cranial base and ratio were reported.

PMID- 24295004
TI  - Adhesion and biofilm formation by periodontopathogenic bacteria on different
      commercial brackets.
AB  - AIM: To compare early bacterial adhesion and biofilm formation of common and
      uncommon periodontal pathogens on a variety of commercial brackets in vitro.
      MATERIALS AND METHODS: In vitro adhesion and biofilm formation of 4 bacterial
      strains on 15 different commercial brackets, in standard culture mediums with and
      without addition of either serum or human saliva was evaluated by quantitative
      real time PCR after extraction of bacterial DNA. RESULTS: Materials significantly
      influenced bacterial adhesiveness in a species-specific way. Titanium and gold
      brackets constantly yielded the lowest values with all tested bacteria and in all
      tested conditions. Bracket materials and medium of growth significantly
      influenced biofilm formation. CONCLUSION: Materials and environmental conditions
      significantly influence biofilm formation by periodontal pathogens at the surface
      of brackets. Whenever possible brackets should be kept far from the gingival
      margin and if this is not possible, brackets made of gold, titanium, and ceramic
      should be preferentially used.

PMID- 24295005
TI  - Understanding MIH: definition, epidemiology, differential diagnosis and new
      treatment guidelines.
AB  - AIM: Molar-Incisor Hypomineralisation (MIH) is a congenital disease which
      increases in prevalence. It affects permanent first molars and, often to a lesser
      degree, permanent incisors with variable severity. The aetiology is unknown, but
      different hypotheses have been advanced. Differential diagnosis is mandatory not
      to confound MIH with other diseases. Treatment consists in a minimally invasive
      approach by reinforcing and protecting the existing dental structure. In more
      severe cases, restorative treatment may be indicated.

PMID- 24295006
TI  - Effect of caries removal techniques on the bond strength of adhesives to caries
      affected primary dentin in vitro.
AB  - AIM: The aim of this in vitro study is to evaluate the effects of three different
      caries removal techniques on the microtensile bond strength of adhesive materials
      to caries-affected dentin. MATERIALS AND METHODS: Thirty primary molar teeth were
      used. The teeth were randomly divided into three groups according to the caries
      removal technique employed: conventional steel bur (group 1); Er:YAG laser (group
      2); chemomechanical method (group 3). Each group was divided into two subgroups
      according to bonding agents: one-step self-etch adhesive and etch-and-rinse
      adhesive. The teeth were restored with composite resin. Vertical sticks were
      obtained and subjected to tensile stress. Data were analyzed by two-way analysis
      of variance (ANOVA), Tukey's test and an independent samples t-test. RESULTS: The
      values for the laser groups were significantly lower than those of the bur groups
      for both bonding agents (p<0.05). There were no significant differences between
      the bur and chemomechanical groups (p > 0.05). CONCLUSION: Bur and
      chemomechanical techniques in primary teeth were found more successful. Similar
      results were found according to the adhesives used for each caries removal
      techniques.

PMID- 24295007
TI  - Association of passive smoking with dental development in young children.
AB  - AIM: To assess dental development in young children who have been exposed to
      passive smoking by comparing dental ages with the corresponding features in a
      healthy control group. MATERIALS AND METHODS: A total of 90 passive smokers (PS)
      with a mean age of 5.49 years and 90 healthy age-matched controls were included
      in this study. The children were investigated for stimulated salivary cotinine
      level. Three categories were formed with respect to the number of cigarettes
      smoked. Dental development was analysed using panoramic radiographs. RESULTS: The
      dose-response relationship between the cotinine levels of the PS subjects and the
      number of cigarettes smoked per day was found to be significantly different for
      the three exposure categories. A significant difference was found between the
      chronological and dental ages of PS subjects when compared with those of the
      control group, but there were no significant differences in dental ages related
      to gender in both groups. CONCLUSION: We could clearly conclude that young
      children who were PS subjects had delayed dental development.

PMID- 24295008
TI  - Adolescent patients' experience with the Carriere distalizer appliance.
AB  - AIM: To examine adolescent patients' experience with the Carriere Distalizer
      Appliance (CDA) and compare it with that of the Forsus Fatigue Resistant Device
      (FFRD). MATERIALS AND METHODS: A survey was administered to 42 patients treated
      with the CDA and 70 patients treated with the FFRD. Amount of time required to
      become accustomed to the appliance, how many patients experienced side effects as
      well as the degree of discomfort were explored. RESULTS: The overall experience
      with the device was significantly better for the CDA group than for the FFRD
      group. Both groups felt that delivery and removal of the appliance was quick and
      easy, the appliance was noticeable to some extent, and the majority became
      accustomed to it within two weeks with a maximum of one month. In general,
      associated discomfort and effects on daily life and activities were less for the
      CDA group than for the FFRD group. Side effects decreased over time for both
      groups, often more so for the CDA group. The major side effects experienced by
      the CDA group were difficulty eating and sore teeth, and these improved
      significantly over time. Soreness from the appliance rubbing on the cheek or lip
      was significantly less for the CDA group. CONCLUSION: The CDA appears to be more
      comfortable, offers a more positive overall experience, and has fewer negative
      comfort-related side effects compared to FFRD.

PMID- 24295009
TI  - Demirjian's system for estimating dental age among Northwestern Turkish children
      aged 4-16 years.
AB  - AIM: The aim of this study was to investigate the timing of individual tooth
      formation stages in a group of northwestern Turkish children and to evaluate the
      suitability of Demirjian's method. MATERIALS AND METHODS:  STUDY DESIGN: dental
      ages (DAs) were assessed from 1,678 digital panoramic radiographs of healthy
      children (aged 4-16 years; 743 females and 935 males). Seven mandibular teeth
      were evaluated according to the Demirjian's eight-grade dental maturity scale by
      one examiner. Dental age was compared to chronologic age (CA) using a paired t
      test. Intra- and inter-observer agreements were assessed with 250 OPGs. RESULTS:
      The mean difference between DA and CA was statistically significant among genders
      (p = 0.004), and it was 0.50 +/-1.90 years in girls and 0.77+/-1.86 years in
      boys. The mean DA was significantly higher (p<0.0001) than the mean CA in the
      entire studied group; therefore, dental development was considerably accelerated.
      The Intra- and Interclass Correlation Coefficient (ICC) for the assessment of DA
      were 0.964 and 0.961, respectively, which is considered "substantial agreement".
      CONCLUSION: Results show that the mean DAs of the studied group of Turkish
      children are significantly higher than the CAs. Overestimation is notable at the
      beginning of puberty.

PMID- 24295010
TI  - Orthodontic treatment timing in growing patients.
AB  - AIM: The aim of the study is to estimate the orthodontic treatment timing for the
      main occlusal problems in growing patients. MATERIALS AND METHODS:  STUDY DESIGN:
      a cross-sectional study was carried out in Italian primary and secondary schools
      from 2008 to 2011; 1375 males and 1642 females, aged between 8 and 13 years, were
      visited. The sample is divided into two main groups: primary school and secondary
      school. Selected malocclusion signs were registered according to an occlusal
      index (ROMA index) by trained and calibrated operators. Prevalence of increased
      overjet, Class III malocclusion, crossbite, deep bite and open bite observed in
      each group are compared. A significant decrease of prevalence with age is
      considered a sign of spontaneous improvement of the malocclusion. RESULTS:
      Descriptive analyses were performed using frequencies, percentages and chi-square
      tests to evaluate differences for categorical variables. The level of
      significance was set at p <=0.05. Data were analysed with the software SPSS 19.0
      for Windows. Class III malocclusion, moderate or severe crossbite and severe
      increased overjet and overbite seem not to improve spontaneously. CONCLUSION:
      Early treatment of orthodontic problems that do not improve with age may be
      helpful to avoid worsening of the condition in permanent dentition. Moderate
      Class II malocclusion and crossbite treatment can be postponed.

PMID- 24295011
TI  - Public community orthodontics in Italy. Description of an experience.
AB  - AIM: To assess the reliability and simplicity of a method chosen for selecting
      subjects to be treated in the orthodontic system and for the acceptance of the
      method by the community. MATERIALS AND METHODS: 490 orthodontic patients received
      full dental examination. For each patient a table was prepared for the detection
      of malocclusion in which the occlusal characteristics according to the Norwegian
      Orthodontic Treatment Index (NOTI), the molar class and the teeth present were
      recorded. The parents of the examined children completed a questionnaire aimed at
      identifying their social ranking. In the same questionnaire, how many siblings
      the patient had was also asked. Each of the three parameters were rated
      alphanumerically and a score of 1 was given to each child; the sum of three
      scores gave the final result for the subject. Acceptance of the procedure in the
      general community was evaluated by the number of complaints received by the
      Public Relations Office (URP). RESULTS: The social classes most represented in
      the sample are "blue collar class" (42.2%) and "white collar class" (35.6%).
      There was an average of 2.1 children per family (SD=0.6). The distribution of the
      type and grading of the treatment need was similar throughout the different
      social classes. CONCLUSION: The chosen method proved reliable for two reasons: no
      complaints with the local URP and ease of application of the selected criteria.

PMID- 24295012
TI  - Molar incisor hypomineralisation and dental caries among children in Slovenia.
AB  - AIM: To assess the prevalence of molar incisor hypomineralisation (MIH) in
      children in Slovenia and explore the relationship between MIH defects and caries
      in the primary and permanent dentition, and tooth- and surface-specific
      associations between MIH defects and caries on first permanent molars (FPM).
      MATERIALS AND METHODS: The study population was comprised of 558 children aged
      6.011.5 years. The prevalence of developmental defects of enamel (DDE) on FPM and
      permanent incisors was assessed through clinical examination by a calibrated
      examiner using the modified DDE Index of the FDI. Also recorded were atypical
      fillings, post-eruptive enamel breakdowns, and extractions because of MIH. Dental
      caries was assessed using the WHO criteria. RESULTS: At least one FPM with MIH
      defects was found in 21.4% of children. Children with MIH had significantly
      higher (p<0.05) caries experience in their permanent teeth. In primary teeth,
      higher caries experience was not statistically significant. MIH defects in FPM
      were associated with higher caries scores at the tooth (p<0.01), and at the
      surface (p<0.05) level. CONCLUSION: MIH is common in Slovenia. Children with MIH
      are more prone to dental caries development on their permanent teeth. On FPM
      teeth and surfaces affected with MIH defects, even with only mild demarcated
      opacities with apparently intact enamel, an increased caries experience is
      present.

PMID- 24295013
TI  - Comparison of microleakage of different margin types around Class V resin
      restorations in primary teeth.
AB  - AIM: This in vitro study compared the effect of a concave with a straight
      bevelled cavity margin on the microleakage of Class V composite resin
      restorations in primary teeth. MATERIALS AND METHODS: Standardised Class V cavity
      preparations were made in vitro on the buccal (all margins placed in enamel) and
      on the lingual (margins placed in enamel and cementum) surfaces of 20 sound
      primary molars. The teeth were randomly assigned to two groups of 10 each: in
      Group 1, a concave bevel was made with a high-speed No. 04 tungsten carbide bur
      and in Group 2, a straight bevel was made with a high-speed No. 556 tungsten
      carbide bur. The teeth were restored incrementally with Adper Single Bond 2 (3M)
      adhesive and Filtek Z 350 (3M) composite resin. All specimens were subsequently
      thermocycled and immersed in 50% silver nitrate solution. Microleakage of the
      restorations was then assessed by silver penetration. A grading scale of 0 to 4
      was used as the scoring criterion. RESULTS: At the enamel margins no
      statistically significant differences were observed between the two groups
      (p>>0.05). Occlusal walls in enamel, in both groups, exhibited less leakage than
      the cervical walls in cementum (p<0.01) and Group 1 showed better results than
      Group 2 in decreasing microleakage at the cementum margins (p <0.05). CONCLUSION:
      Based on the results, it was concluded that concave-beveled cavity preparations
      may reduce but did not totally eliminate microleakage at the cementum margins of
      Class V composite resin restorations in primary teeth.

PMID- 24295014
TI  - A qualitative exploration of how individuals reconstruct their sense of self
      following acquired brain injury in comparison with spinal cord injury.
AB  - PRIMARY OBJECTIVE: The present study aimed to investigate the specific ways in
      which individuals reconstruct their sense of self following injury to the nervous
      system, by comparing individuals with acquired brain injury (ABI) and individuals
      with spinal cord injury (SCI), two groups that have experienced a sudden-onset
      injury with life-changing repercussions. RESEARCH DESIGN: Phenomenological
      qualitative research. METHODS AND PROCEDURES: Nine individuals with ABI and 10
      individuals with SCI took part in an interview exploring the ways in which
      individuals reconstruct their sense of self following injury. Data were analysed
      using interpretative thematic analysis. MAIN OUTCOMES AND RESULTS: Findings
      showed similar themes identified within the interview data of the ABI and SCI
      groups. Both groups developed positive and negative self-narratives. Individuals
      employed strategies that facilitated the reconstruction of positive self
      narratives. In addition, individuals described their sense of self as
      simultaneously continuous and changing. DISCUSSION: Findings are discussed in
      relation to proposed models of self-reconstruction post-injury to the nervous
      system.

PMID- 24295015
TI  - Phytochemicals in sweet sorghum ( Dura ) and their antioxidant capabilities
      against lipid oxidation.
AB  - Hydrophilic (HPE) and lipophilic (LPE) extracts were obtained from the Louisiana
      sweet sorghum millets. Nine major hydrophilic phytochemicals were quantified at
      levels of 8.9 MUg/g for cinnamic acid to 1570.0 MUg/g for apigeninidin.
      Lipophilic phytochemicals (alpha- and gamma-tocopherol, lutein, and beta
      carotene) were quantified at levels of 7.7, 145.7, 4.8, and 18.8 MUg/g,
      respectively. The total phenolic contents of HPE and LPE were 768.9 and 97.6 MUg
      of catechin equivalent/g, respectively, while DPPH activities were 6.5 and 0.8
      MUmol of Trolox equivalent/g for HPE and LPE, respectively. In an emulsion model,
      HPE exhibited higher capability of inhibiting cholesterol oxidation and
      stabilizing linoleic acid than LPE. Inhibition rates of cholesterol oxidation for
      HPE and LPE at 40 MUg/mL were 92.2% and 65.4%, respectively. Retention rates of
      linoleic acid were 70.4% for HPE and 33.6% for LPE at a given concentration.
      Thus, HPE of sweet sorghum millet has potential in functional food applications. 

PMID- 24295018
TI  - Nanomaterials in analytical chemistry.

PMID- 24295019
TI  - Whole cell quenched flow analysis.
AB  - This paper describes a microfluidic quenched flow platform for the investigation
      of ligand-mediated cell surface processes with unprecedented temporal resolution.
      A roll-slip behavior caused by cell-wall-fluid coupling was documented and acts
      to minimize the compression and shear stresses experienced by the cell. This
      feature enables high-velocity (100-400 mm/s) operation without impacting the
      integrity of the cell membrane. In addition, rotation generates localized
      convection paths. This cell-driven micromixing effect causes the cell to become
      rapidly enveloped with ligands to saturate the surface receptors. High-speed
      imaging of the transport of a Janus particle and fictitious domain numerical
      simulations were used to predict millisecond-scale biochemical switching times.
      Dispersion in the incubation channel was characterized by microparticle image
      velocimetry and minimized by using a horizontal Hele-Shaw velocity profile in
      combination with vertical hydrodynamic focusing to achieve highly reproducible
      incubation times (CV = 3.6%). Microfluidic quenched flow was used to investigate
      the pY1131 autophosphorylation transition in the type I insulin-like growth
      factor receptor (IGF-1R). This predimerized receptor undergoes
      autophosphorylation within 100 ms of stimulation. Beyond this demonstration, the
      extreme temporal resolution can be used to gain new insights into the mechanisms
      underpinning a tremendous variety of important cell surface events. 

PMID- 24295020
TI  - Synthesis, activity, and QSAR studies of tryptamine derivatives on third-instar
      larvae of Aedes aegypti Linn.
AB  - Special attention has been given to the mosquito Aedes aegypti Linn. (Diptera:
      Culicidae) owing to numerous dengue epidemic outbreaks worldwide. Failure to
      control vector spreading is accounted for unorganized urban growth and resistance
      to larvicides and insecticides. Therefore, researchers are currently searching
      for new and more efficient larvicides and insecticides to aid dengue control
      measures. Triptamine is known to affect insect behavior, development, and
      physiology. Expression of this compound in plants has reduced the growth rate of
      herbivore insects. In view of these facts, it was of our interest to synthesize
      triptamine amide derivatives as potential larvicides against Ae. aegypti,
      establishing a Structure-Activity Relationship. Eleven amide derivatives of
      triptamine were synthesized, characterized, and evaluated for their larvicidal
      activity against third-instar Ae. aegypti larvae. N-(2-(1H-indol-3-yl)ethyl)
      2,2,2-trichloroacetamide exhibited the highest overall larvicidal potency, while
      N-(2-(1H-Indol-3-yl)ethyl) acetamide displayed the lowest larvicidal potency. A
      regression equation correlating the larvicidal activity with Log P was obtained.
      We have found a clear relationship between the larvicidal activity of non
      chlorinated compounds and Log P. Analysis of the relationship between Log P and
      larvicidal activity against Ae. aegypti may be useful in the evaluation of
      potential larvicidal compounds. 

PMID- 24295022
TI  - Costs and beliefs: understanding individual- and neighborhood-level correlates of
      medication nonadherence among Mexican Americans with type 2 diabetes.
AB  - OBJECTIVE: High rates of medication nonadherence observed in disadvantaged
      populations are often attributed to socioeconomic factors. Little is known,
      however, about how a person's neighborhood environment may contribute to
      nonadherence beyond what can be explained by a lack of individual resources to
      pay for medications. This study considered the reasons patients reported for
      deviating from their medication regimens to understand how individual-level and
      neighborhood-level indicators of socioeconomic status (SES) may each influence
      adherence behavior. METHOD: Cross-sectional data were collected between 2006 and
      2011 from a sample of Mexican American patients with type 2 diabetes (N = 749)
      treated at university-affiliated clinics in Southern California. Measures
      included individual-level SES (years of education, health insurance type, and
      household income), neighborhood deprivation, and medication nonadherence (for
      reasons related to cost and reasons related to beliefs about medications).
      Neighborhood deprivation was assessed using the Neighborhood Socioeconomic Status
      Index (Dubowitz et al., 2011), a validated aggregate of census tract-level
      indicators linked to each participant's home address. RESULTS: RESULTS from
      multilevel logistic regression models revealed that individual-level SES was
      associated with nonadherence related to cost (annual household income < $20,000
      vs. > $40,000, p = .001; Medicare vs. commercial health insurance, p < .001),
      whereas neighborhood deprivation was associated with nonadherence related to
      beliefs about medications (p = .011). CONCLUSION: Findings from this study
      suggest that an individual's lack of resources may contribute to nonadherence
      related to cost, whereas elements of the broader social environment may promote
      nonadherence related to negative beliefs about medications.

PMID- 24295023
TI  - Increasing colonoscopies? A psychological perspective on opting in versus opting
      out.
AB  - OBJECTIVE: A growing strategy to enhancing healthy decision making is to modify
      behavioral options to an "opt out" (i.e., if you do not want to participate, you
      must act) as opposed to an "opt in" (i.e., if you want to participate, you must
      act) default system (Choi, Laibson, Madrian, & Metrick). The current study,
      however, proposes that this growing trend may not always be strategic and
      examines these default systems in colonoscopy appointment show-up rates. METHODS:
      Participants in an opt-in condition received instructions to call and schedule
      their colonoscopy appointment, whereas participants in an opt-out condition were
      mailed the date and time of an already scheduled appointment. We then assessed
      colonoscopy appointment show-up rates. RESULTS: As predicted, results revealed
      significant decrements in the show-up rates of those in the opt-out (63%) versus
      opt-in condition, 85%; chi2 (1) = 5.51, p = .02. Furthermore, when looking at
      patients who confirmed their appointment in both conditions, only 3% of opt-in
      (vs. 21% of opt-outpatients) no-showed, chi2 (1) = 4.51, p = .03. CONCLUSION:
      Although modifying the default to an opt-out system has been shown to be
      effective in some health care procedures, the current results reveal this system
      is not always effective in producing the healthiest medical behaviors. Our
      research, then, suggests that opt-out paradigms are not an overall panacea for
      increasing participation in preventive health. (PsycINFO Database Record (c) 2014
      APA, all rights reserved).

PMID- 24295024
TI  - Can we improve cognitive-behavioral therapy for chronic back pain treatment
      engagement and adherence? A controlled trial of tailored versus standard therapy.
AB  - OBJECTIVE: This study evaluated whether tailored cognitive-behavioral therapy
      (TCBT) that incorporated preferences for learning specific cognitive and/or
      behavioral skills and used motivational enhancement strategies would improve
      treatment engagement and participation compared with standard CBT (SCBT). We
      hypothesized that participants receiving TCBT would show a lower dropout rate,
      attend more sessions, and report more frequent intersession pain coping skill
      practice than those receiving SCBT. We also hypothesized that indices of
      engagement and adherence would correlate with pre- to posttreatment changes in
      outcome factors. METHOD: One hundred twenty-eight of 161 consenting persons with
      chronic back pain who completed baseline measures were allocated to either TCBT
      or SCBT using a modified randomization procedure. Participants completed daily
      ratings of pain coping skill practice and goal accomplishment during treatment,
      as well as measures of pain severity, disability, and other key outcomes at the
      end of treatment. RESULTS: No significant differences between treatment groups
      were noted on measures of treatment engagement or adherence. However, these
      factors were significantly related to some pre- to posttreatment improvements in
      outcomes, regardless of treatment condition. CONCLUSIONS: Participants in this
      study evidenced a high degree of participation and adherence, but treatment
      tailored to take into account participant preferences, and that employed
      motivational enhancement strategies, failed to increase treatment participation
      over and above SCBT for chronic back pain. Evidence that participation and
      adherence were associated with positive outcomes supports continued clinical and
      research efforts focusing on these therapeutic processes.

PMID- 24295025
TI  - Prompting healthier eating: testing the use of health and social norm based
      messages.
AB  - OBJECTIVE: Health based messages are commonly used to promote fruit and vegetable
      intake, but are limited in their effectiveness. Social norm messages, which
      suggest other people are eating healthily, may be more effective. Our aim was to
      compare the effect on food selection of a message containing health related
      information about fruit and vegetable consumption with a message containing
      social normative information about consumption of fruit and vegetables. METHOD:
      In two laboratory studies, predominantly young female adult students were exposed
      to a health or social norm message about fruit and vegetables. In Study 1, lunch
      meal food selections and intake were assessed and in Study 2, snack food
      selections and intake were assessed. Study 1 examined the effect of a descriptive
      social norm (information about what others are eating) versus a health message
      and Study 2 examined the effect of both a descriptive norm and an injunctive norm
      message (information about what others approve of) versus a health message.
      RESULTS: In Study 1, exposure to a descriptive social norm message resulted in
      significantly more vegetables being selected and eaten than exposure to a health
      message. In Study 2, exposure to a descriptive social norm message resulted in
      significantly more fruit and vegetables and less high energy dense snack food
      being selected and eaten than exposure to a health message. There was no effect
      of exposure to the injunctive norm message. In both studies, significant
      differences between the social norm and health message conditions were observed
      in low but not high usual consumers of fruit and vegetables. CONCLUSIONS: For the
      promotion of healthy eating, social norm messages may be more effective than
      health messages for consumers failing to adhere to dietary guidelines.

PMID- 24295027
TI  - Opportunities and challenges in developing stearoyl-coenzyme A desaturase-1
      inhibitors as novel therapeutics for human disease.
AB  - This review provides an overview of stearoyl-coenzyme A desaturase-1 (SCD1) as a
      novel therapeutic target for metabolic disorders and other indications. Target
      validation is reviewed, and limitations due to incomplete knowledge of the
      relevant biological systems are described. Assay development, particularly for
      high throughput screening, and characterization of SCD1 inhibition are
      summarized. The progress and evolution in medicinal chemistry are discussed,
      specifically focusing on key attributes of the most advanced SCD1 inhibitors
      described in the primary literature and in patent applications. This work
      culminated in numerous companies identifying potent selective inhibitors, some of
      which progressed to early clinical development. The status of current SCD1 drug
      discovery programs is reviewed. Challenges are discussed, and potential new
      directions are indicated. 

PMID- 24295026
TI  - Health problems among low-income parents in the aftermath of Hurricane Katrina.
AB  - OBJECTIVE: Although the mental health consequences of disasters have been well
      documented, relatively less is known about their effects on survivors' physical
      health. Disaster studies have also generally lacked predisaster data, limiting
      researchers' ability to determine whether postdisaster physical health problems
      were influenced by disaster exposure, or whether they would have emerged even if
      the disaster had not occurred. The current study aimed to fill this gap. METHOD:
      Participants were low-income, primarily non-Hispanic Black mothers (N = 334) who
      survived Hurricane Katrina and completed 4 survey assessments, 2 predisaster and
      2 postdisaster. In each assessment, participants reported on whether they had
      experienced 3 common health problems (frequent headaches or migraines, back
      problems, and digestive problems) and completed 2 mental health measure (the K6
      scale, the Perceived Stress Scale). RESULTS: The descriptive results suggested
      that the hurricane led to at least short-term increases in the 3 health outcomes.
      Fixed effects modeling was conducted to explore how changes in various predictor
      variables related to changes in each health condition over the study. Bereavement
      and increases in psychological distress were significant predictors of increases
      in health problems. CONCLUSIONS: Based on these results, further research that
      explores the processes through which disasters lead to both physical and mental
      health problems, postdisaster screenings for common health conditions and
      psychological distress, and interventions that boost survivors' stress management
      skills are suggested.

PMID- 24295028
TI  - Impact of unilateral tubal blockage diagnosed by hysterosalpingography on the
      success rate of treatment with controlled ovarian stimulation and intrauterine
      insemination.
AB  - The aim of this study was to evaluate the success rates of intrauterine
      insemination (IUI) in infertile women with unilateral proximal and distal tubal
      blockage. A total of 161 couples with unilateral tubal blockage and unexplained
      infertility were included. The primary outcome measure was the cumulative
      pregnancy rate (CPR). The CPRs after three cycles of IUI were 26.3% (10/38) in
      patients with unilateral tubal blockage, and 44.7% (55/123) in patients with
      unexplained infertility (p = 0.043). CPRs were similar in patients with proximal
      unilateral tubal blockage and unexplained infertility (38.1% vs 44.7%,
      respectively, p = 0.572). CPR was significantly lower in patients with distal
      unilateral tubal blockage than in patients with unexplained infertility (11.7% vs
      44.7%, respectively, p = 0.01). In conclusion, IVF instead of IUI may be a more
      appropriate approach for distal unilateral tubal blockage patients. 

PMID- 24295029
TI  - Imag(in)ing trans partnerships: collaborative photography and intimacy.
AB  - In this article, I argue that collaborative photography offers dynamic potential
      for imag(in)ing trans intimate partnerships beyond the authority of textual
      representation. I present five photographic and narrative case studies, spanning
      a range of trans partnerships in the UK, to demonstrate some of the complex ways
      in which bodies, genders, sexualities, and time intersect in trans intimacy. I
      argue that the photographs create an imaginative resource, both for the people
      depicted in the photographs and for those viewing the photographs, providing new
      possibilities for thinking about trans partnerships, expanding the ways in which
      trans intimate partnerships are imag(in)ed, and opening up new spaces of
      possibility for gender and sexual identities.

PMID- 24295030
TI  - A physiologically based toxicokinetic model for the zebrafish Danio rerio.
AB  - Zebrafish (Danio rerio) is a widely used model for toxicological studies, in
      particular those related to investigations on endocrine disruption. The
      development and regulatory use of in vivo and in vitro tests based on this
      species can be enhanced by toxicokinetic modeling. For this reason, we propose a
      physiologically based toxicokinetic (PBTK) model for zebrafish describing the
      uptake and disposition of organic chemicals. The model is based on literature
      data on zebrafish, other cyprinidae and other fish families, new experimental
      physiological information (volumes, lipids and water contents) obtained from
      zebrafish, and chemical-specific parameters predicted by generic models. The
      relevance of available models predicting the latter parameters was evaluated with
      respect to gill uptake and partition coefficients in zebrafish. This evaluation
      benefited from the fact that the influence of confounding factors such as body
      weight and temperature on ventilation rate was included in our model. The
      predictions for six chemicals (65 data points) yielded by our PBTK model were
      compared to available toxicokinetics data for zebrafish and 88% of them were
      within a factor of 5 of the corresponding experimental values. Sensitivity
      analysis highlighted that the 1-octanol/water partition coefficient, the
      metabolism rate, and all the parameters that enable the prediction of
      assimilation efficiency and partitioning of chemicals need to be precisely
      determined in order to allow an effective toxicokinetic modeling. 

PMID- 24295031
TI  - Relating chemical structure to device performance via morphology control in
      diketopyrrolopyrrole-based low band gap polymers.
AB  - We investigated the structure-morphology-performance relationship of
      diketopyrrolopyrrole (DPP)-based low band gap polymers with different donor cores
      in organic field effect transistors (OFETs) and organic photovoltaics (OPVs). The
      change in the chemical structure led to strong physical property differences,
      such as crystalline behavior, blend morphology, and device performance. In
      addition, the choice of solvents and additives enabled one to fine tune the
      properties of these materials in the condensed state. For instance, when thin
      films were processed from solvent mixtures, both in the pure polymer and in a
      blend, we observed an enhanced edge-on orientation and the formation of thinner
      and longer polymer fibrils. In the BHJ blends, processing from a solvent mixture
      reduced the size scale of the phase separation and promoted the formation of a
      fibrillar network morphology, having a polymer-PCBM mixture filling the
      interfibrillar regions. The characteristic length scale of the fibrillar network
      dictated the specific inner surface area, which directly correlated to the
      performance in the OPV devices. When the BHJ mixture was processed from a single
      solvent, a large-scale phase separated morphology was observed that was
      stratified, normal to the film surface. A strong scattering anisotropy was
      observed in the resonant soft X-ray scattering of the blends that provided
      insight into the packing of the polymer chains within the fibrils. The morphology
      and performance trend in OPVs paralleled the performance in an OFET, suggesting
      that similar processing conditions should be considered in OFET fabrication. 

PMID- 24295032
TI  - Cardiovascular autonomic neuropathy in type 2 diabetes mellitus patients with
      peripheral artery disease.
AB  - OBJECTIVE: To evaluate possible associations between cardiovascular autonomic
      dysfunction and peripheral artery disease (PAD) in patients with type 2 diabetes
      mellitus. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 67 patients
      with type 2 diabetes were included. PAD was identified by Doppler
      ultrasonography: systolic ankle-brachial pressure index <0.9. Cardiovascular
      autonomic function, besides five conventional cardiovascular autonomic function
      tests, was assessed by heart rate variability (HRV; 24-h ambulatory ECG
      recording) in time and frequency domains (spectral analyses) and three
      dimensional return maps. Power spectral analyses (PSA) were quantified in low
      frequency (LF), high frequency (HF), and very low frequency. RESULTS: Patients
      with PAD (n = 30) had longer diabetes duration, higher systolic blood pressure
      (BP), waist-to-hip ratio, HbA1C test, and urinary albumin excretion (UAE) than
      patients without PAD. Most HRV indices in time domain were lower in patients with
      than without PAD. These patients also had lower PSA indices (LF=0.19+/-0.07 vs.
      0.29+/-0.11 n.u.; LF/HF ratio=1.98+/-0.9 vs. 3.35+/-1.83; P< 0.001) and indices
      of sympathetic (three-dimensional return map: P1-night 61.7+/-9.4 vs. 66.8+/-9.7;
      P=0.04) and vagal (24-h P2 54.5+/-15.2 vs. 62.7+/-2.9; P< 0.02) activities
      (arbitrary units) than patients without PAD. Multivariate logistic regression
      analyses, adjusted for systolic BP, DM duration, HbA1C test, and UAE, confirmed
      the associations between impaired autonomic modulation and PAD, except for P1
      index. CONCLUSION: In conclusion, patients with type 2 diabetes with PAD had
      lower HRV indices than patients without PAD, reflecting a dysfunction of
      cardiovascular autonomic modulation.

PMID- 24295033
TI  - Ultrathin oriented BiFeO3 films from deposition of atomic layers with greatly
      improved leakage and ferroelectric properties.
AB  - Highly (001)-oriented BiFeO3 ultrathin films of total thickness of less than 10
      nm were deposited on Si(001) substrates via deposition of atomic layers (ALD)
      with a LaNiO3 buffer. A radio-frequency (RF)-sputtered sample of the same
      thickness was prepared for comparison. The ALD combined with interrupted flow and
      an exchange reaction between Bi and Fe precursors provides a superior method to
      grow ternary compounds. According to X-ray diffraction, upon deposition at a
      temperature of less than 550  degrees C, the only phase in the film was BiFeO3.
      Anomalous fine structure from synchrotron X-ray diffraction certified the valence
      bonding through the BiFeO3 (001) diffraction signal. The stoichiometric ratio of
      BiFeO3 obtained from X-ray photoelectron spectroscopy indicated that ALD has a
      proportion much improved over the RF preparation, and this is also in agreement
      with the results for diffraction anomalous fine structure. The use of high
      resolution transmission electron and atomic force microscopes showed that the
      layer structure and morphology from ALD presented a satisfactory coverage, more
      conformal than that with the RF method. The BiFeO3 thin film deposited with ALD
      shows excellent leakage, improved at least 1000 times with respect to the RF
      preparation, making this method suitable for the fabrication of ferroelectric
      random-access memory devices. From the hysteresis loop, the largest remanent
      polarization was observed as 2Pr = 2.0 MUC cm(-2). 

PMID- 24295034
TI  - Evaluating the efficacy of tuberculosis Advocacy, Communication and Social
      Mobilization (ACSM) activities in Pakistan: a cross-sectional study.
AB  - BACKGROUND: Tuberculosis (TB) continues to be a major public health and
      development problem within many low- and middle-income countries. Although
      Advocacy, Communication and Social Mobilization (ACSM) activities have been
      undertaken in high TB burden countries to remediate these issues, there is little
      empirical evidence of the efficacy of these approaches. The purpose of this study
      was therefore to examine the efficacy of an ACSM program undertaken within
      Pakistan. Pakistan was chosen because it has received considerable funding for
      ACSM related activities and is one of 22 high-burden TB countries. METHODS: The
      program was evaluated by surveying a stratified random sample of 2,400
      participants across 57 districts of Pakistan. Participants were categorized into
      one of three groups: aware of both media and community ACSM activities
      (AwareMedia&Community), aware of ACSM media activities only (AwareMedia), or
      unaware of any ACSM activities (UnawareMedia&Community). RESULTS: Independent
      measures ANCOVA revealed complex differences in knowledge, attitudes, and
      intended behaviors towards TB between the three groups. In general,
      UnawareMedia&Community cases had a poorer understanding of TB and its treatment,
      whilst awareness of ACSM activities was highest among literate and urban dwelling
      Pakistanis. Preferred sources of TB information were also found to vary by
      gender, geographic location, and literacy. CONCLUSIONS: Whilst highlighting
      improvements in knowledge and attitudes toward TB, the results also provide
      invaluable insights into areas where further work needs to be done to address
      deficits in TB understanding, particularly among rural and illiterate Pakistanis.
      Equally important, the findings have implications for future TB ACSM initiatives
      in Pakistan in terms of leveraging the preferred media channels of key
      demographic segments and exploring the degree to which exposure to multiple
      channels of communication may have an additive effect on health knowledge.

PMID- 24295035
TI  - State-dependent rotational diffusion of tetracene in n-alkanes. Evidence for a
      dominant energy relaxation pathway.
AB  - We have investigated the rotational diffusion of tetracene in the n-alkanes
      octane through hexadecane. Emission from the S1 state was monitored following
      excitation to the S1 state or the S2 state. Our data show that fast, non
      radiative relaxation from S2 to S1 gives rise to local heating in the immediate
      vicinity of the chromophore. This local heating effect exhibits a solvent
      aliphatic chain length dependence for solvents C11 and longer, where solvents
      with an even number of carbons behave differently than those with an odd number
      of carbons. These data shed light on the possible origin(s) of odd-even effects
      in n-alkanes and suggest that a dominant intermolecular relaxation pathway for
      excess vibrational energy involves the S1 chromophore ring breathing mode (ca.
      1383 cm(-1)) and the solvent terminal methyl group rocking mode (1375 cm(-1)). 

PMID- 24295037
TI  - Objectively measured physical activity and sedentary behaviour of Yakut (Sakha)
      adults.
AB  - BACKGROUND: Circumpolar regions are undergoing social and economic transition,
      which often corresponds to a behavioural transition. Yet, physical activity and
      sedentary behaviour are rarely objectively measured within these groups. AIM:
      This study aimed to characterize objectively measured physical activity and
      sedentary behaviour in a sample of indigenous Siberians. SUBJECTS AND METHODS:
      Yakut (Sakha) adults (n = 68, 32 men) underwent anthropometry, interviews and
      wore a triaxial accelerometer for two days. Time spent in moderate-to-vigorous
      physical activity (MVPA) or sedentary behaviour was calculated using a single
      axis and also all three axes. RESULTS: Men spent significantly more time in MVPA
      than women, although no sex difference was found in sedentary behaviour.
      Participants were far more active and less sedentary when classified using all
      three axes (vector magnitude) than a single axis. Television viewing time
      significantly related to sedentary behaviour in men only. CONCLUSION: The Yakut
      have gender differences in amount and predictors of physical activity and
      sedentary behaviour. Triaxial accelerometry is more sensitive to daily physical
      activity in free living populations than single axis.

PMID- 24295036
TI  - Internet-delivered, family-based treatment for early-onset OCD: a preliminary
      case series.
AB  - Given the burdens of early-onset obsessive-compulsive disorder (OCD), limitations
      in the broad availability and accessibility of evidence-based care for affected
      youth present serious public health concerns. The growing potential for
      technological innovations to transform care for the most traditionally remote and
      underserved families holds enormous promise. This article presents the rationale,
      key considerations, and a preliminary case series for a promising behavioral
      telehealth innovation in the evidence-based treatment of early-onset OCD. We
      developed an Internet-based format for the delivery of family-based treatment for
      early-onset OCD directly to families in their homes, regardless of their
      geographic proximity to a mental health facility. Videoteleconferencing (VTC)
      methods were used to deliver real-time cognitive-behavioral therapy centering on
      exposure and response prevention to affected families. Participants in the
      preliminary case series included 5 children between the ages of 4 and 8 (M Age =
      6.5) who received the Internet-delivered treatment format. All youth completed a
      full treatment course, all showed OCD symptom improvements and global severity
      improvements from pre- to posttreatment, all showed at least partial diagnostic
      response, and 60% no longer met diagnostic criteria for OCD at posttreatment. No
      participants got worse, and all mothers characterized the quality of services
      received as "excellent." The present work adds to a growing literature supporting
      the potential of VTC and related computer technology for meaningfully expanding
      the reach of supported treatments for OCD and lays the foundation for subsequent
      controlled evaluations to evaluate matters of efficacy and engagement relative to
      standard in-office evidence-based care.

PMID- 24295038
TI  - The negative impact of traumatic brain injury (TBI) on bone in a mouse model.
AB  - INTRODUCTION: While it is well established that the brain produces hypothalamic
      hormones and neuropeptides that influence skeletal metabolism, the impact of
      traumatic brain injury (TBI) on bone is unknown. Based on the recognition from
      clinical studies that there is an association between TBI and long-term
      hypothalamic pituitary dysfunction, it was hypothesized that TBI exerts a
      negative impact on skeletal growth and maintenance. METHODS: To test the
      hypothesis, this study employed a repetitive weight drop model for TBI. Four
      impacts were applied for four consecutive days on 5-week old female C57BL/6 J
      mice. Bone measurements were taken 2 weeks after the first impact. RESULTS: Bone
      mineral content (BMC), bone area (B area) and bone mineral density (BMD) in the
      total body were reduced by 14.5%, 9.8% and 5.2%, respectively, in the impacted
      vs. control mice. There was a 17.1% reduction in total volumetric BMD (vBMD) and
      a 4.0% reduction in material vBMD in cortical bone. In trabecular bone, there was
      a 44.0% reduction in BV/TV. Although there was no change in the cross-sectional
      bone size, the tibial growth plate and the tibia itself were shortened.
      CONCLUSION: The repetitive animal TBI model produced an immediate, strong
      negative impact on bone mass acquisition in young mice.

PMID- 24295039
TI  - Advances in P-glycoprotein-based approaches for delivering anticancer drugs:
      pharmacokinetic perspective and clinical relevance.
AB  - INTRODUCTION: P-glycoprotein (P-gp) is a multi-specific efflux transporter
      belonging to ATP-binding cassette (ABC) transporter family, encoded by the ABCB1
      gene, which significantly impacts the pharmacokinetics as well as multidrug
      resistance of anticancer drugs. AREAS COVERED: This review explores how human P
      gp transporters modulate the pharmacokinetics of anticancer drugs and emerging
      strategies to modulate their function. The key findings in direct modulation by
      various P-gp inhibitors on pharmacokinetics of various anticancer P-gp substrates
      are described. The role of pharmaceutical excipients as P-gp inhibitor with the
      focus on the recent development in novel drug delivery systems to modulate
      pharmacokinetics of anticancer drugs is also outlined. EXPERT OPINION: The
      concomitant use of anticancer P-gp substrate and P-gp inhibitor is an effective
      and safe way to enhance the bioavailability of anticancer drugs. The poor
      bioavailability and toxicity of anticancer drugs limit their therapeutic
      efficacy. These characteristics can be improved by using various nanocarriers
      which exhibited a high potential to bypass this efflux protein. The best
      combination of P-gp inhibitor and substrate anticancer drug in a single
      nanocarrier formulation is a future challenge and is still probably some years
      away from the marketplace.

PMID- 24295040
TI  - Immature platelet fraction levels in a variety of bone marrow pathologies in
      South African HIV-positive patients with thrombocytopenia.
AB  - OBJECTIVES: Thrombocytopenia is common in HIV-infected individuals and often
      requires a diagnostic bone marrow examination. Interpretation may, however, be
      limited due to the multifactorial nature of HIV-associated thrombocytopenia and
      the difficulty in assessing megakaryocyte function morphologically. The immature
      platelet fraction (IPF) is a parameter which reportedly reflects megakaryocyte
      activity, with an IPF >7.7% suggesting increased platelet production. The aim of
      this study was to correlate the IPF with the bone marrow findings as well as
      other clinical variables of interest in South African patients with HIV
      associated thrombocytopenia. METHODS: Seventy-eight HIV-positive patients with
      thrombocytopenia were enrolled from the Charlotte Maxeke Johannesburg Academic
      Hospital. The IPF levels were measured using a Sysmex XE-5000 haematology
      analyzer and were correlated with bone marrow and other findings. RESULTS: The
      median IPF was 7.6%, ranging from 1.3 to 44%. It was raised in 78% of patients
      with immune thrombocytopenia (ITP) (median = 16.3%) and low in 79% of patients
      with hypocellular marrow (median = 6.5%). Surprisingly, it was highly variable
      among patients with malignant marrow infiltration and mycobacterial infection of
      the bone marrow (BMTB) (median = 8.4 and 7.1%, respectively). Multivariate linear
      regression analysis confirmed a significant independent inverse relationship
      between the IPF and hypocellular marrow (P < 0.0001), a marginally significant
      positive association with ITP (P = 0.059), and the absence of any relationship
      with malignant infiltration or BMTB. The IPF had a significant inverse
      association with the platelet count (P = 0.0006), but was unrelated to the CD4
      count and exposure to anti-retroviral therapy. Unexpectedly, it showed a
      significant positive association with the HIV viral load (P = 0.005). We
      speculate this to reflect increased megakaryocyte activity in compensation for
      accelerated platelet clearance due to HIV-driven platelet activation. CONCLUSION:
      This study investigates the role of the IPF in HIV-associated thrombocytopenia,
      and emphasizes the limitations of morphological analysis in determining
      megakaryocyte function.

PMID- 24295041
TI  - The effect of divided attention on emotion-induced memory narrowing.
AB  - Individuals are more likely to remember emotional than neutral information, but
      this benefit does not always extend to the surrounding background information.
      This memory narrowing is theorised to be linked to the availability of
      attentional resources at encoding. In contrast to the predictions of this
      theoretical account, altering participants' attentional resources at encoding by
      dividing attention did not affect emotion-induced memory narrowing. Attention was
      divided using three separate manipulations: a digit ordering task (Experiment 1),
      an arithmetic task (Experiment 2) and an auditory discrimination task (Experiment
      3). Across all three experiments, divided attention decreased memory across the
      board but did not affect the degree of memory narrowing. These findings suggest
      that theories to explain memory narrowing must be expanded to include other
      potential mechanisms beyond the limitations of attentional resources. 

PMID- 24295042
TI  - Chlorogenic acid and coffee prevent hypoxia-induced retinal degeneration.
AB  - This study explored whether chlorogenic acid (CGA) and coffee have protective
      effects against retinal degeneration. Under hypoxic conditions, the viability of
      transformed retinal ganglion (RGC-5) cells was significantly reduced by treatment
      with the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP). However,
      pretreatment with CGA attenuated cell death in a concentration-dependent manner.
      In addition, CGA prevented the up-regulation of apoptotic proteins such as Bad
      and cleaved caspase-3. Similar beneficial effects of both CGA and coffee extracts
      were observed in mice that had undergone an optic nerve crush (ONC) procedure.
      CGA and coffee extract reduced cell death by preventing the down-regulation of
      Thy-1. Our in vitro and in vivo studies demonstrated that coffee and its major
      component, CGA, significantly reduce apoptosis of retinal cells induced by
      hypoxia and NO, and that coffee consumption may help in preventing retinal
      degeneration. 

PMID- 24295043
TI  - American Thyroid Association statement on optimal surgical management of goiter.
AB  - BACKGROUND: Goiter, or benign enlargement of the thyroid gland, can be
      asymptomatic or can cause compression of surrounding structures such as the
      esophagus and/or trachea. The options for medical treatment of euthyroid goiter
      are short-lived and are limited to thyroxine hormone suppression and radioactive
      iodine ablation. The objective of this statement article is to discuss optimal
      surgical management of goiter. METHODS: A task force was convened by the Surgical
      Affairs Committee of the American Thyroid Association and was tasked with writing
      of this article. RESULTS/CONCLUSIONS: Surgical management is recommended for
      goiters with compressive symptoms. Symptoms of dyspnea, orthopnea, and dysphagia
      are more commonly associated with thyromegaly, in particular, substernal goiters.
      Several studies have demonstrated improved breathing and swallowing outcomes
      after thyroidectomy. With careful preoperative testing and thoughtful
      consideration of the type of anesthesia, including the type of intubation,
      preparation for surgery can be optimized. In addition, planning the extent of
      surgery and postoperative care are necessary to achieve optimal results. Close
      collaboration of an experienced surgical and anesthesia team is essential for
      induction and reversal of anesthesia. In addition, this team must be cognizant of
      complications from massive goiter surgery such as bleeding, airway distress,
      recurrent laryngeal nerve injury, and transient hypoparathyroidism. With careful
      preparation and teamwork, successful thyroid surgery can be achieved.

PMID- 24295044
TI  - An ethnobotanical study of medicinal plants in Wayu Tuka District, East Welega
      Zone of Oromia Regional State, West Ethiopia.
AB  - BACKGROUND: This paper reports an ethnobotanical study that focused on the
      traditional medicinal plants used by local communities to treat human and
      livestock ailments. A cross-sectional study was undertaken from September 2009 to
      June 2010 in Wayu Tuka District of Oromia Region, Ethiopia. The aim of the study
      is to document medicinal plants used by local people of the study area and the
      threats currently affecting medicinal plants. METHODS: Ethnobotanical data were
      collected using semi-structured interviews, field observations and group
      discussion in which 63 (41 men & 22 women) randomly selected informants
      participated. Of which, 11 (10 male and 1 female) were local healers. Paired
      comparison method, direct matrix ranking and Informant consensus factors (ICF)
      were used to analyze the importance of some plant species. RESULTS: A total of
      126 medicinal plant species, distributed in 108 genera and 56 families, were
      collected together with their medicinal uses. Of the 126 species of medicinal
      plants collected from the study area, eighty six (68%) were obtained from the
      wild whereas thirty three (26%) were from homegardens. The Fabaceae came out as a
      leading family with 15 medicinal species while the Solanaceae followed with eight
      species. Seventy eight (62%) of the medicinal plants were reported as being used
      for treating human ailments, 23 (18.2%) for the treatment of livestock ailments
      and 25 (20%) for both. The most frequently used plant parts were leaves (43%),
      followed by roots (18.5%) while crushing, which accounted for (29%) and powdering
      (28%) were the widely used methods of preparation of traditional herbal
      medicines. CONCLUSION: The number of reported medicinal plants and their uses by
      the local people of the District indicate the depth of the local indigenous
      knowledge on medicinal plants and their application. The documented medicinal
      plants can serve as a basis for future investigation of modern drug.

PMID- 24295045
TI  - Neisseria meningitidis endogenous endophthalmitis with meningitis in an
      immunocompetent child.
AB  - Neisseria meningitidis is a major cause of childhood morbidity and mortality
      worldwide. We describe an exceptional case of an immunocompetent 15-month-old
      child presenting with a unilateral anterior uveitis, hypopyon, and sepsis.
      Anterior chamber aspirate demonstrated gram-negative cocci before Neisseria
      meningitidis was identified in blood and cerebrospinal fluid. Meningococcal
      endophthalmitis presents variably with sepsis, meningitis, or isolated ocular
      symptoms. Diagnosis is a clinical challenge, requiring diagnostic sampling and
      treatment from both pediatricians and ophthalmologists. Delayed or incorrect
      treatment risks blindness, disability, or death. Simultaneous invasion of
      meningococcus across intact blood-brain and blood-ocular barriers in this child
      suggests antigenic correlates between meningeal and ocular endothelial
      interfaces. Meningococcus is an exclusively human pathogen; research is hampered
      by the lack of animal models. This clinical observation suggests the potential of
      a novel in vitro experimental approach of using ocular tissue from eye banks to
      further elucidate the meningococcal-endothelial interaction that underpins
      meningococcal disease.

PMID- 24295046
TI  - Design, synthesis, and biological evaluation of 1-phenylpyrazolo[3,4
      e]pyrrolo[3,4-g]indolizine-4,6(1H,5H)-diones as new glycogen synthase kinase
      3beta inhibitors.
AB  - Compound 5 was selected from our in-house library as a suitable starting point
      for the rational design of new GSK-3beta inhibitors. MC/FEP calculations of 5 led
      to the identification of a structural class of new GSK-3beta inhibitors. Compound
      18 inhibited GSK-3beta with an IC50 of 0.24 MUM and inhibited tau phosphorylation
      in a cell-based assay. It proved to be a selective inhibitor of GSK-3 against a
      panel of 17 kinases and showed >10-fold selectivity against CDK2. Calculated
      physicochemical properties and Volsurf predictions suggested that compound 18 has
      the potential to diffuse passively across the blood-brain barrier.

PMID- 24295047
TI  - Toward a generalized and high-throughput enzyme screening system based on
      artificial genetic circuits.
AB  - Large-scale screening of enzyme libraries is essential for the development of
      cost-effective biological processes, which will be indispensable for the
      production of sustainable biobased chemicals. Here, we introduce a genetic
      circuit termed the Genetic Enzyme Screening System that is highly useful for high
      throughput enzyme screening from diverse microbial metagenomes. The circuit
      consists of two AND logics. The first AND logic, the two inputs of which are the
      target enzyme and its substrate, is responsible for the accumulation of a phenol
      compound in cell. Then, the phenol compound and its inducible transcription
      factor, whose activation turns on the expression of a reporter gene, interact in
      the other logic gate. We confirmed that an individual cell harboring this genetic
      circuit can present approximately a 100-fold higher cellular fluorescence than
      the negative control and can be easily quantified by flow cytometry depending on
      the amounts of phenolic derivatives. The high sensitivity of the genetic circuit
      enables the rapid discovery of novel enzymes from metagenomic libraries, even for
      genes that show marginal activities in a host system. The crucial feature of this
      approach is that this single system can be used to screen a variety of enzymes
      that produce a phenol compound from respective synthetic phenyl-substrates,
      including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and
      methyl parathion hydrolase. Consequently, the highly sensitive and quantitative
      nature of this genetic circuit along with flow cytometry techniques could provide
      a widely applicable toolkit for discovering and engineering novel enzymes at a
      single cell level. 

PMID- 24295048
TI  - beta-Octamethoxyporphycenes.
AB  - Porphycene with eight methoxy substituents at its beta-positions was synthesized
      for the first time in three steps from 3,4-dimethoxypyrrole. The presence of
      methoxy groups increases its hydrophilicity as evident from their increased
      solubility in methanol. Among its metallo-derivatives, the Pd(II)-complex
      displays efficient singlet oxygen quantum yield (73%) and hence can be a
      potentially good photosensitizer for photo-oxidation, DNA cleavage, and
      photodynamic therapy (PDT). 

PMID- 24295049
TI  - Physical and sexual violence and symptoms of gynaecological morbidity among
      married young women in India.
AB  - Evidence from India about young women's experience of physical and sexual
      violence within marriage and its sexual and reproductive health consequences is
      limited. Data, drawn from 12,220 married women ages 15-24 years old from six
      Indian states, were used to identify associations between the experience of
      violence and recent symptoms of gynaecological morbidity, using logistic
      regression analysis. Young women who had experienced physical, sexual, or both
      forms of violence in the 12 months preceding the interview were more likely than
      others to report symptoms of gynaecological morbidity (odds ratios, 1.8-2.1);
      associations were evident in all six states. However, associations were weak
      between those who had experienced violence earlier in marriage but not in the 12
      months preceding the interview and those who had never experienced violence.
      Findings highlight the need for the health system to play a proactive role in
      recognising and responding to the needs of young women experiencing marital
      violence. 

PMID- 24295050
TI  - Ca2+/S100 proteins inhibit the interaction of FKBP38 with Bcl-2 and Hsp90.
AB  - FKBP38 (FK506-binding protein 38), a membrane-anchored TPR (tetratricopeptide
      repeat)-containing immunophilin, regulates signalling pathways such as cell
      survival, apoptosis, proliferation and metastasis. However, the mechanisms that
      regulate the activity of FKBP38 are, at present, poorly understood. We previously
      reported that Ca2+/S100 proteins directly associate with the TPR proteins, such
      as Hop [Hsp70 (heat-shock protein of 70 kDa)/Hsp90-organizing protein], kinesin
      light chain, Tom70 (translocase of outer mitochondrial membrane 70), FKBP52,
      CyP40 (cyclophilin 40), CHIP (C-terminus of Hsc70-interacting protein) and PP5
      (protein phosphatase 5), leading to the dissociation of the interactions of the
      TPR proteins with their target proteins. Therefore we have hypothesized that
      Ca2+/S100 proteins can interact with FKBP38 and regulate its function. In vitro
      binding studies demonstrated that S100A1, S100A2, S100A6, S100B and S100P
      specifically interact with FKBP38 and inhibit the interaction of FKBP38 with Bcl
      2 and Hsp90. Overexpression of permanently active S100P in Huh-7 cells inhibited
      the interaction of FKBP38 with Bcl-2, resulting in the suppression of Bcl-2
      stability. The association of the S100 proteins with FKBP38 provides a Ca2+
      dependent regulatory mechanism of the FKBP38-mediated signalling pathways.

PMID- 24295051
TI  - Surgical treatment of late-onset amniotic fluid pulmonary embolism.

PMID- 24295052
TI  - Ionic conductivity of mixed glass former 0.35Na(2)O + 0.65[xB(2)O(3) + (1 -
      x)P(2)O(5)] glasses.
AB  - The mixed glass former effect (MGFE) is defined as a nonlinear and nonadditive
      change in the ionic conductivity with changing glass former fraction at constant
      modifier composition between two binary glass forming compositions. In this
      study, mixed glass former (MGF) sodium borophosphate glasses, 0.35Na2O +
      0.65[xB2O3 + (1 - x)P2O5], 0 <= x <= 1, have been prepared, and their sodium
      ionic conductivity has been studied. The ionic conductivity exhibits a strong,
      positive MGFE that is caused by a corresponding strongly negative nonlinear,
      nonadditive change in the conductivity activation energy with changing glass
      former content, x. We describe a successful model of the MGFE in the conductivity
      activation energy terms of the underlying short-range order (SRO) phosphate and
      borate glass former structures present in these glasses. To do this, we have
      developed a modified Anderson-Stuart (A-S) model to explain the decrease in the
      activation energy in terms of the atomic level composition dependence (x) of the
      borate and phosphate SRO structural groups, the Na(+) ion concentration, and the
      Na(+) mobility. In our revision of the A-S model, we carefully improve the
      treatment of the cation jump distance and incorporate an effective Madelung
      constant to account for many body coulomb potential effects. Using our model, we
      are able to accurately reproduce the composition dependence of the activation
      energy with a single adjustable parameter, the effective Madelung constant, that
      changes systematically with composition, x, and varies by no more than 10% from
      values typical of oxide ceramics. Our model suggests that the decreasing columbic
      binding energies that govern the concentration of the mobile cations are
      sufficiently strong in these glasses to overcome the increasing volumetric strain
      energies (mobility) caused by strongly increasing glass-transition temperatures
      combined with strongly decreasing molar volumes of these glasses. The dependence
      of the columbic binding energy term on the relative high-frequency dielectric
      permittivity suggests that the increased polarizability of the bridging oxygens
      connecting SRO tetrahedral boron units to phosphorus units causes further charge
      delocalization away from the negatively charged tetrahedral boron units, leading
      to a lowering of the charge density, and is the underlying cause of the MGFE. 

PMID- 24295053
TI  - Excellent performance of one-pot synthesized Cu-SSZ-13 catalyst for the selective
      catalytic reduction of NOx with NH3.
AB  - Cu-SSZ-13 samples prepared by a novel one-pot synthesis method achieved excellent
      NH3-SCR performance and high N2 selectivity from 150 to 550  degrees C after ion
      exchange treatments. The selected Cu3.8-SSZ-13 catalyst was highly resistant to
      large space velocity (800 000 h(-1)) and also maintained high NOx conversion in
      the presence of CO2, H2O, and C3H6 in the simulated diesel exhaust. Isolated
      Cu(2+) ions located in three different sites were responsible for its excellent
      NH3-SCR activity. Primary results suggest that the one-pot synthesized Cu-SSZ-13
      catalyst is a promising candidate as an NH3-SCR catalyst for the NOx abatement
      from diesel vehicles. 

PMID- 24295054
TI  - Crystal structure of a promoter sequence in the B-raf gene reveals an intertwined
      dimer quadruplex.
AB  - The sequence d(GGGCGGGGAGGGGGAAGGGA) occurs in the promoter region of the B-raf
      gene. An X-ray crystallographic study has found that this forms an unprecedented
      dimeric quadruplex arrangement, with a core of seven consecutive G-quartets and
      an uninterrupted run of six potassium ions in the central channel of the
      quadruplex. Analogy with previously reported promoter quadruplexes had initially
      suggested that in common with these a monomeric quadruplex was to be expected.
      The structure has a distorted G.C.G.C base quartet at one end and four flipped
      out adenosine nucleosides at the other. The only loops in the structure are
      formed by the cytosine and by the three adenosines within the sequence, with all
      of the guanosines participating in G-quartet formation. Solution UV and circular
      dichroism data are in accord with a stable quadruple arrangement being formed. 1D
      NMR data, together with gel electrophoresis measurements, are consistent with a
      dimer being the dominant species in potassium solution. A single-chain
      intramolecular quadruplex has been straightforwardly constructed using molecular
      modeling, by means of a six-nucleotide sequence joining 3' and 5' ends of each
      strand in the dimer. A human genomic database search has revealed a number of
      sequences containing eight or more consecutive short G-tracts, suggesting that
      such intramolecular quadruplexes could be formed within the human genome. 

PMID- 24295055
TI  - Trans people's experience of sexuality in the Netherlands: a pilot study.
AB  - This pilot study explores the specificity of 12 Dutch trans people's experience
      of sexuality in order to provide new hypotheses and perspectives for future
      research. Emerging themes include the interconnection of sexual development with
      coming out and transition processes, the way incongruence between gender
      identity, gendered embodiment, and social perception of gender affected
      participants' experience of sexuality, and changes in physical sexual functioning
      after hormone therapy and/or various types of surgery. Our research design
      allowed for subjective accounts of trans people's experience of sexuality and
      detailed descriptions of changes in sexuality that occurred over time and
      throughout the coming out and transitioning processes.

PMID- 24295057
TI  - Diagnosis and prevention of thalassemia.
AB  - Thalassemia is the most common monogenic inherited disease worldwide and it
      affects most countries to various extents. This review summarizes the current
      approaches to phenotypic and genotypic diagnosis of thalassemia in clinical
      practice. Prevention strategies that encompass carrier screening, genetic
      counseling and prenatal diagnosis are discussed. The importance of public
      education and an awareness of a changing perception regarding this group of
      diseases are emphasized. It also addresses the impact of the rapidly increasing
      knowledge in disease severity modification by hemoglobin F (Hb F).

PMID- 24295058
TI  - Inborn errors of metabolism and expanded newborn screening: review and update.
AB  - Inborn errors of metabolism (IEM) are a phenotypically and genetically
      heterogeneous group of disorders caused by a defect in a metabolic pathway,
      leading to malfunctioning metabolism and/or the accumulation of toxic
      intermediate metabolites. To date, more than 1000 different IEM have been
      identified. While individually rare, the cumulative incidence has been shown to
      be upwards of 1 in 800. Clinical presentations are protean, complicating
      diagnostic pathways. IEM are present in all ethnic groups and across every age.
      Some IEM are amenable to treatment, with promising outcomes. However, high
      clinical suspicion alone is not sufficient to reduce morbidities and mortalities.
      In the last decade, due to the advent of tandem mass spectrometry, expanded
      newborn screening (NBS) has become a mandatory public health strategy in most
      developed and developing countries. The technology allows inexpensive
      simultaneous detection of more than 30 different metabolic disorders in one
      single blood spot specimen at a cost of about USD 10 per baby, with commendable
      analytical accuracy and precision. The sensitivity and specificity of this method
      can be up to 99% and 99.995%, respectively, for most amino acid disorders,
      organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies
      have confirmed that the savings achieved through the use of expanded NBS programs
      are significantly greater than the costs of implementation. The adverse effects
      of false positive results are negligible in view of the economic health benefits
      generated by expanded NBS and these could be minimized through increased
      education, better communication, and improved technologies. Local screening
      agencies should be given the autonomy to develop their screening programs in
      order to keep pace with international advancements. The development of
      biochemical genetics is closely linked with expanded NBS. With ongoing
      advancements in nanotechnology and molecular genomics, the field of biochemical
      genetics is still expanding rapidly. The potential of tandem mass spectrometry is
      extending to cover more disorders. Indeed, the use of genetic markers in T-cell
      receptor excision circles for severe combined immunodeficiency is one promising
      example. NBS represents the highest volume of genetic testing. It is more than a
      test and it warrants systematic healthcare service delivery across the pre
      analytical, analytical, and post-analytical phases. There should be a
      comprehensive reporting system entailing genetic counselling as well as short
      term and long-term follow-up. It is essential to integrate existing clinical IEM
      services with the expanded NBS program to enable close communication between the
      laboratory, clinicians, and allied health parties. In this review, we will
      discuss the history of IEM, its clinical presentations in children and adult
      patients, and its incidence among different ethnicities; the history and recent
      expansion of NBS, its cost-effectiveness, associated pros and cons, and the
      ethical issues that can arise; the analytical aspects of tandem mass spectrometry
      and post-analytical perspectives regarding result interpretation.

PMID- 24295059
TI  - ApoB versus non-HDL-cholesterol: diagnosis and cardiovascular risk management.
AB  - The most recent guidelines released by the EAS/ESC and the Canadian
      Cardiovascular Society (CCS) retain low-density lipoprotein cholesterol (LDL-C)
      as the primary measure of the atherogenic risk of the apolipoprotein B (apoB)
      lipoproteins and the primary target of LDL-C lowering therapy. Both organizations
      endorse non-high-density lipoprotein cholesterol (non-HDL-C) and apoB as
      "alternate/secondary" targets, but neither group offers evidence supporting the
      continued preference of LDL-C as the primary target over non-HDL-C and apoB.
      Further, both suggest that non-HDL-C and apoB more or less measure the same thing
      and, therefore, are essentially interchangeable. But what is the evidence that
      LDL-C should remain the primary target, and are apoB and non-HDL-C mirror images
      of one another? Furthermore, are estimation of risk and establishment of
      treatment targets the only relevant issues, or is diagnosis also an essential
      objective? These are the questions this article will address. Our principal
      objectives are: (1) to clarify the differences between LDL-C, non-HDL-C, and apoB
      and to distinguish what they measure; (2) to summarize the evidence relating to
      LDL-C, non-HDL-C, and apoB as predictors of cardiovascular risk and as targets
      for treatment; and (3) to demonstrate that diagnosis of atherogenic
      dyslipoproteinemias should be a fundamental clinical priority.

PMID- 24295060
TI  - Examining diet- and exercise-related communication in romantic relationships:
      associations with health behaviors.
AB  - This study examined the association between diet- and exercise-related social
      influence and support among romantic partners, as well as whether these variables
      were associated with their health behaviors. An Actor-Partner Mediator Model was
      used to examine these associations at the couple level (n = 192). Results
      indicated that individuals who felt their partners used more positive influence
      strategies also reported feeling more supported by their partners. Further, men
      who reported feeling more supported by their partners also engaged in healthier
      diet and exercise behaviors. Overall, the results suggested that people's
      perceptions of positive communication (i.e., influence and support) from their
      partners were generally more likely to be associated with their enactment of
      healthier behaviors. Implications for intrapersonal as well as interpersonal
      effects of influence, support, and health behaviors are discussed. 

PMID- 24295062
TI  - Investigating industrial investigation: examining the impact of a priori
      knowledge and tunnel vision education.
AB  - The current study addressed tunnel vision in industrial incident investigation by
      experimentally testing how a priori information and a human bias (generated via
      the fundamental attribution error or correspondence bias) affected participants'
      investigative behavior as well as the effectiveness of a debiasing intervention.
      Undergraduates and professional investigators engaged in a simulated industrial
      investigation exercise. We found that participants' judgments were biased by
      knowledge about the safety history of either a worker or piece of equipment and
      that a human bias was evident in participants' decision making. However, bias was
      successfully reduced with "tunnel vision education." Professional investigators
      demonstrated a greater sophistication in their investigative decision making
      compared to undergraduates. The similarities and differences between these two
      populations are discussed.

PMID- 24295063
TI  - Nanoporous glass films on liquids.
AB  - Glass-like thin films are used in many applications as dielectric layers, barrier
      coatings, abrasion-resistant films, and/or transparent films. We report the first
      direct application of such materials to liquid substrates using a plasma
      deposition process at atmospheric pressure. The study demonstrates the broader
      utilization of these materials, for example, as robust membranes for water
      harvesting or drug delivery. 

PMID- 24295064
TI  - 5-HT(1A) receptor: an old target as a new attractive tool in drug discovery from
      central nervous system to cancer.
AB  - The serotonin receptor subtype 5-HT(1A) was one of the first serotonin receptor
      subtypes pharmacologically characterized. This receptor subtype has long been
      object of intense research and is implicated in the pathogenesis and treatment of
      anxiety and depressive disorders. In recent years, new chemical entities
      targeting the 5-HT(1A) receptor (alone or in combination with other molecular
      targets) have been proposed for novel therapeutic uses in neuroprotection,
      cognitive impairment, Parkinson's disease, pain treatment, malignant carcinoid
      syndrome, and prostate cancer. This Perspective compares existing data on
      expression and signaling activity of the 5-HT(1A) receptor to a ligand with an
      intrinsic agonist or antagonist profile. Our purpose is also to make a complete
      overview, useful for underlining the features needed to select a specific
      pharmacological profile rather than another one. This aspect could be really
      interesting to consider and justify the 5-HT(1A) receptor as a new attractive
      target for drug discovery.

PMID- 24295065
TI  - PEGylated nanomedicines: recent progress and remaining concerns.
AB  - INTRODUCTION: Recent biopharma deals related to nanocarrier drug delivery
      technologies highlight the emergence of nanomedicine. This is perhaps an expected
      culmination of many years of research demonstrating the potential of nanomedicine
      as the next generation of therapeutics with improved performance. PEGylated
      nanocarriers play a key role within this field. AREAS COVERED: The drug delivery
      advantages of nanomedicines in general are discussed, focusing on nanocarriers
      and PEGylated nanomedicines, including products under current
      development/clinical evaluation. Well-established drug delivery benefits of
      PEGylation (e.g., prolonged circulation) are only briefly covered. Instead,
      attention is deliberately made to less commonly reported advantages of
      PEGylation, including mucosal delivery of nanomedicines. Finally, some of the
      issues related to the safety of PEGylated nanomedicines in clinical application
      are discussed. EXPERT OPINION: The advent of nanomedicine providing therapeutic
      options of refined performance continues. Although PEGylation as a tool to
      improve the pharmacokinetics of nanomedicines is well established and is used
      clinically, other benefits of 'PEGnology', including enhancement of
      physicochemical properties and/or biocompatibility of actives and/or drug
      carriers, as well as mucosal delivery, have attracted less attention. While
      concerns regarding the clinical use of PEGylated nanomedicines remain, evidence
      suggests that at least some safety issues may be controlled by adequate designs
      of nanosystems.

PMID- 24295066
TI  - Calprotectin (S100A8/A9), S100A12, and EDTA-resistant S100A12 complexes (ERAC) in
      primary Sjogren's syndrome.

PMID- 24295067
TI  - Involvement of mitogen activated protein kinase kinase 6 in UV induced
      transcripts accumulation of genes in phytoalexin biosynthesis in rice.
AB  - BACKGROUND: Ultra violet radiation leads to accumulation of phytoalexins (PA) in
      rice (Oryza sativa) which are typically accumulated when the plants are infected
      with rice blast pathogen Magnaporthe oryzae. Although extensive works have been
      done in elucidating phytoalexin biosynthesis, UV stress signal transduction
      leading to accumulations of rice phytoalexin is largely unknown. RESULTS: In the
      present study, the involvement of mitogen activated protein kinase (MAPK) cascade
      has been shown in UV induced regulation of genes in phytoalexin biosynthesis in
      rice. UV induced activation of MAPK and expression of PA biosynthesis genes were
      shown to be inhibited with staurosporin and MAPK inhibitors. Transcript
      regulation studies and kinase assays indicated involvement of OsMKK6 in the
      process. Transgenic rice overexpressing constitutive active OsMKK6EE exhibited
      higher expression of genes of PA biosynthesis pathway upon UV stress and also
      upon infection with M. oryzae. CONCLUSION: These results suggest a key role of
      OsMKK6 in regulation of UV responsive expression of genes of PA biosynthesis in
      rice. This study will help to elucidate the intricate signalling components of UV
      leading to phytoalexins biosynthesis in rice.

PMID- 24295068
TI  - Common sense: folk wisdom that ethnobiological and ethnomedical research cannot
      afford to ignore.
AB  - Common sense [CS], especially that of the non-scientist, can have predictive
      power to identify promising research avenues, as humans anywhere on Earth have
      always looked for causal links to understand, shape and control the world around
      them. CS is based on the experience of many individuals and is thus believed to
      hold some truths. Outcomes predicted by CS are compatible with observations made
      by whole populations and have survived tests conducted by a plethora of non
      scientists. To explore our claim, we provide 4 examples of empirical insights
      (relevant to probably all ethnic groups on Earth) into causal phenomena predicted
      by CS: (i) "humans must have a sense of time", (ii) "at extreme latitudes, more
      people have the winter blues", (iii) "sleep is a cure for many ills" and (iv)
      "social networks affect health and disease". While CS is fallible, it should not
      be ignored by science - however improbable or self-evident the causal
      relationships predicted by CS may appear to be. 

PMID- 24295070
TI  - Clinical characteristics of scleritis and episcleritis: results from the pacific
      ocular inflammation study.

PMID- 24295069
TI  - Investigation of LKB1 Ser431 phosphorylation and Cys433 farnesylation using mouse
      knockin analysis reveals an unexpected role of prenylation in regulating AMPK
      activity.
AB  - The LKB1 tumour suppressor protein kinase functions to activate two isoforms of
      AMPK (AMP-activated protein kinase) and 12 members of the AMPK-related family of
      protein kinases. The highly conserved C-terminal residues of LKB1 are
      phosphorylated (Ser431) by PKA (cAMP-dependent protein kinase) and RSK (ribosomal
      S6 kinase) and farnesylated (Cys433) within a CAAX motif. To better define the
      role that these post-translational modifications play, we created homozygous
      LKB1S431A/S431A and LKB1C433S/C433S knockin mice. These animals were viable,
      fertile and displayed no overt phenotypes. Employing a farnesylation-specific
      monoclonal antibody that we generated, we established by immunoprecipitation that
      the vast majority, if not all, of the endogenous LKB1 is prenylated. Levels of
      LKB1 localized at the membrane of the liver of LKB1C433S/C433S mice and their
      fibroblasts were reduced substantially compared with the wild-type mice,
      confirming that farnesylation plays a role in mediating membrane association.
      Although AMPK was activated normally in the LKB1S431A/S431A animals, we
      unexpectedly observed in all of the examined tissues and cells taken from
      LKB1C433S/C433S mice that the basal, as well as that induced by the AMP-mimetic
      AICAR (5-amino-4-imidazolecarboxamide riboside), AMPK activation, phenformin and
      muscle contraction were significantly blunted. This resulted in a reduced ability
      of AICAR to inhibit lipid synthesis in primary hepatocytes isolated from
      LKB1C433S/C433S mice. The activity of several of the AMPK-related kinases
      analysed [BRSK1 (BR serine/threonine kinase 1), BRSK2, NUAK1 (NUAK family, SNF1
      like kinase 1), SIK3 (salt-inducible kinase 3) and MARK4 (MAP/microtubule
      affinity-regulating kinase 4)] was not affected in tissues derived from
      LKB1S431A/S431A or LKB1C433S/C433S mice. Our observations reveal for the first
      time that farnesylation of LKB1 is required for the activation of AMPK. Previous
      reports have indicated that a pool of AMPK is localized at the plasma membrane as
      a result of myristoylation of its regulatory AMPKbeta subunit. This raises the
      possibility that LKB1 farnesylation and myristoylation of AMPKbeta might promote
      the interaction and co-localization of these enzymes on a two-dimensional
      membrane surface and thereby promote efficient activation of AMPK.

PMID- 24295072
TI  - Heart rate variability in neurorehabilitation patients with severe acquired brain
      injury.
AB  - INTRODUCTION: Acquired brain injury (ABI) cause neural deficits. In addition to
      motor and cognitive deficits, the autonomic nervous system may be affected. This
      has been shown for neurorehabilitation patients with traumatic brain injury (TBI)
      by means of reduced heart rate variability (HRV). It was hypothesized that
      patient groups with other ABI aetiology (mainly stroke, subarachnoid haemorrhage
      and anoxia) would also present reduced HRV. METHODS: Patients consecutively
      admitted and severely ABI injured were considered for HRV measurements. HRV was
      extracted as a mean of four 5-minute ECG recordings at 6 pm, 10 pm, 2 am and 6 am
      the following day (scheduled resting periods). One 5-minute HRV recording from a
      sex- and age-matched group of healthy volunteers constituted control data.
      Standard deviation of normal-to-normal intervals (SDNN) and low frequency (LF)
      were primary HRV variables. RESULTS: Of 71 admitted patients, HRV was extracted
      from 49 patients. Patient SDNN and LF were reduced compared to controls (SDNN: 13
      ms (CI = [10.8; 15.3]) vs 40.3 ms (CI = [36.6; 44.2]), p < 0.0001; LF: 29.4 ms2
      (CI = [19.8; 43.7]) vs 518 ms2 (CI = [419; 639]), p < 0.0001). HRV appeared
      identical across ABI aetiology. CONCLUSION: It was found that HRV was
      considerably reduced in an heterogenic ABI patient group admitted for
      neurorehabilitation.

PMID- 24295071
TI  - Is human immunodeficiency virus (HIV) stage an independent risk factor for
      altering the periodontal status of HIV-positive patients? A South African study.
AB  - BACKGROUND: The immunosuppresion in HIV patients makes them highly susceptible to
      microbial infections. The aim of the study was to establish whether HIV stage (as
      depicted by CD4+ T lymphocyte counts) could independently be associated with
      periodontal status (as revealed by the measurement of clinical indices). METHODS:
      One hundred and twenty HIV-infected patients attending an infectious diseases
      clinic in the Western Cape, South Africa were included in the study. The
      periodontal clinical indices such as plaque index, gingival index, pocket probing
      depth and clinical attachment levels were measured on the mesial aspect of the
      six Ramfjord teeth. The CD4 + T cell counts were taken from the patients' medical
      records and patients' HIV stage determined and grouped according to their CD4+ T
      cell counts into A (<200 cells /mm3), B (200-500 cells /mm3) and C (>500 cells
      /mm3). RESULTS: The mean age of 120 HIV-positive patients was 33.25 years and the
      mean CD4 + T cell count was 293.43 cells/mm3. The probing depth and clinical
      attachment loss were found to be significantly associated with the total CD4 + T
      cell counts but not with HIV stage. Significant correlations were found between
      age and all clinical indices except for clinical attachment loss. No correlation
      was found between age and HIV stage of the patients. The use of antiretroviral
      therapy was significantly associated with probing depth and clinical attachment
      loss, but not with plaque nor gingival index. Significant associations were
      observed between smoking and all of the clinical indices except for the gingival
      index. A significant association was observed between the use of interdental aids
      and all the clinical indices except for probing depth, while brushing was
      significantly associated with plaque index only. CD4 + T cell counts were
      significantly associated with brushing frequency (p = 0.0190) and the use of
      interdental aids (p = 0.0170). CONCLUSION: The findings of this study conclude
      that HIV stage, ART and age are not independent risk factors for changes in the
      periodontal status of HIV-positive subjects but rather that smoking and oral
      hygiene habits determine their susceptibility to disease.

PMID- 24295073
TI  - General applicability of synthetic gene-overexpression for cell-type ratio
      control via reprogramming.
AB  - Control of the cell-type ratio in multistable systems requires wide-range control
      of the initial states of cells. Here, using a synthetic circuit in E. coli, we
      describe the use of a simple gene-overexpression system combined with a bistable
      toggle switch, for the purposes of enabling the wide-range control of cellular
      states and thus generating arbitrary cell-type ratios. Theoretically,
      overexpression induction temporarily alters the bistable system to a monostable
      system, in which the location of the single steady state of cells can be
      manipulated over a wide range by regulating the overexpression levels. This
      induced cellular state becomes the initial state of the basal bistable system
      upon overexpression cessation, which restores the original bistable system. We
      experimentally demonstrated that the overexpression induced a monomodal cell
      distribution, and subsequent overexpression withdrawal generated a bimodal
      distribution. Furthermore, as designed theoretically, regulating the
      overexpression levels by adjusting the concentrations of small molecules
      generated arbitrary cell-type ratios. 

PMID- 24295074
TI  - Conformational biases of linear motifs.
AB  - Linear motifs (LMs) are protein-protein interaction sites, typically consisting
      of ~4-20 amino acid residues that are often found in disordered proteins or
      regions, and function largely independent from other parts of the proteins they
      are found in. These short sequence patterns are involved in a wide spectrum of
      biological functions including cell cycle control, transcriptional regulation,
      enzymatic catalysis, cell signaling, protein trafficking, etc. Even though LMs
      may adopt defined structures in complexes with targets, which can be determined
      by conventional methods, their uncomplexed states can be highly dynamic and
      difficult to characterize. This hinders our understanding of the structure
      function relationship of LMs. Here, the uncomplexed states of 6 different LMs are
      investigated using atomistic molecular dynamics (MD) simulations. The total
      simulation time was about 63 MUs. The results show that LMs can have distinct
      conformational propensities, which often resemble their complexed state. As a
      result, the free state structure and dynamics of LMs may hold important clues
      regarding binding mechanisms, affinities and specificities. The findings should
      be helpful in advancing our understanding of the mechanisms whereby disordered
      amino acid sequences bind targets, modeling disordered proteins/regions, and
      computational prediction of binding affinities.

PMID- 24295075
TI  - Directed orthometalation and the asymmetric total synthesis of N
      deoxymilitarinone A and torrubiellone B.
AB  - A diverted total synthesis (DTS) approach to the total synthesis of pyridone
      alkaloids N-deoxymilitarinone A (8) and torrubiellone B (10) has been developed.
      The common intermediate 14 was first assembled by a dual directed orthometalation
      process using a methoxymethyl group as directed metalation group. Other crucial
      steps include the assembly of polyenes under aldol condensation for DTS using
      general and concise strategy and diastereoselective synthesis of the syn-dimethyl
      array by an Evans aldol reaction. 

PMID- 24295076
TI  - The impact of iodinated contrast agent administered during preoperative computed
      tomography scan on body iodine pool in patients with differentiated thyroid
      cancer preparing for radioactive iodine treatment.
AB  - BACKGROUND: Iodine in iodinated contrast agents (ICAs) interferes with
      radioactive iodine treatment (RAIT) and diagnostic scans in patients with
      differentiated thyroid carcinoma (DTC) because it can compete with 131I.
      Published guidelines recommend delaying RAIT for three to four months in patients
      who have been exposed to ICA. Spot urinary iodine concentration is a useful
      marker to reflect the body iodine pool. We investigated the impact of ICAs
      administered at preoperative computed tomography (CT) scan on the body iodine
      pool to determine the proper time interval between preoperative CT and RAIT in
      DTC patients. METHODS: We performed a retrospective review of 1023 patients with
      DTC who underwent a preoperative CT scan with ICA, total thyroidectomy, and one
      week of low-iodine diet in preparation for RAIT. Urine iodine excretion (UIE) was
      measured in spot urine by inductively coupled plasma mass spectrometry and
      reported both in simple concentration (MUg/L) and divided by gram creatinine
      (MUg/gCr). Patients were divided into five groups by time interval in days
      between preoperative CT scan and spot urine iodine measurement (A, 31-60 [n=29];
      B, 61-90 [n=155]; C, 91-120 [n=546]; D, 121-150 [n=226]; E, 151-180 [n=67]).
      RESULTS: The median (interquartile range) of UIE (MUg/gCr) in each group was 44.4
      (27.7-73.2) in group A, 33.3 (22.8-64.7) in group B, 32.7 (20.8-63.0) in group C,
      32.0 (20.6-67.0) in group D, and 30.4 (19.6-70.8) in group E. There was no
      significant difference between group A and the remaining groups (p>0.05) Also,
      the proportion of patients who achieved the appropriate UIE for RAIT according to
      our hospital's cutoff (<=66.2 MUg/gCr) was not different between groups (A,
      72.4%; B, 76.1%; C, 77.5%; D, 74.8%; E, 74.6%) (p=0.78). CONCLUSION: This study
      shows that a UIE of one month after preoperative CT scan with ICA was not higher
      than that of six months after CT scan in patients who underwent total
      thyroidectomy for DTC. Thus, current guidelines that recommend delay of RAIT for
      three to four months after CT scan with ICA should be revisited and future
      studies to clarify the appropriate time interval between CT scan with ICA and
      RAIT are warranted.

PMID- 24295078
TI  - When selves have sex: what the phenomenology of trans sexuality can teach about
      sexual orientation.
AB  - In this article, Bettcher argues that sexual attraction must be reconceptualized
      in light of transgender experience. In particular, Bettcher defends the theory of
      "erotic structuralism," which replaces an exclusively other-directed account of
      gendered attraction with one that includes a gendered eroticization of self as an
      essential component. This erotic experience of self is necessary for other
      directed gendered desire, where the two are bound together and mutually
      informing. One consequence of the theory is that the controversial notion of
      "autogynephilia" is rejected. Another consequence is that the distinction between
      gender identity and sexual orientation is softened. 

PMID- 24295077
TI  - Opposite effects of anxiety and depressive symptoms on executive function: the
      case of selecting among competing options.
AB  - People constantly face the need to choose one option from among many, such as
      when selecting words to express a thought. Selecting between many options can be
      difficult for anyone, and can feel overwhelming for individuals with elevated
      anxiety. The current study demonstrates that anxiety is associated with impaired
      selection across three different verbal tasks, and tests the specificity of this
      finding to anxiety. Anxiety and depression frequently co-occur; thus, it might be
      assumed that they would demonstrate similar associations with selection, although
      they also have distinct profiles of symptoms, neuroanatomy and neurochemistry.
      Here, we report for the first time that anxiety and depressive symptoms counter
      intuitively have opposite effects on selection among competing options.
      Specifically, whereas anxiety symptoms are associated with impairments in verbal
      selection, depressive symptoms are associated with better selection performance.
      Implications for understanding the mechanisms of anxiety, depression and
      selection are discussed. 

PMID- 24295079
TI  - Anisotropic colloidal micromuscles from liquid crystal elastomers.
AB  - Monodomain liquid crystal elastomers (LCEs) are new materials uniquely suitable
      for artificial muscles, as they undergo large reversible uniaxial shape changes,
      with strains of 20-500% and stresses of 10-100 kPa, falling exactly into the
      dynamic range of a muscle. LCEs exhibit little to no fatigue over thousands of
      actuation cycles. Their practical use has been limited, however, owing to the
      difficulty of synthesizing components, achieving consistent alignment during
      cross-linking across the whole material and often a high nematic-isotropic phase
      transition temperature. The most widely studied method for LC alignment involves
      mechanical stretching of the material during one of two cross-linking steps,
      which makes fabrication difficult to control and lends itself mainly to samples
      that can be easily grasped (with sizes of the order of mm). In this article, we
      describe a method of adapting the LCE synthesis to microscale objects, achieving
      monodomain alignment with a single cross-linking step, and lowering the cycling
      temperature. LCE precursor droplets are embedded in and then stretched in a
      polymer matrix at high temperature. Confinement of the uniaxially stretched
      droplets maintains the alignment achieved during stretching and allows us to
      eliminate one of the cross-linking steps and the variability associated with it.
      Adding a comonomer during the polymerization leads to lowering of the nematic-to
      isotropic transition temperature (58  degrees C), significantly expanding the
      range of potential applications for these micromuscles. We demonstrate reversible
      thermal switching of the micromuscles in line with the largest strain changes
      observed for side-chain LCEs and a differential scanning calorimetry
      characterization of the material phase transitions. The method demonstrates the
      parallel fabrication of many microscale actuators and is amenable to further
      scale-up and manufacturing. 

PMID- 24295080
TI  - Dietary patterns of Akwesasne Mohawk adolescents.
AB  - BACKGROUND: Native American youth have greater rates of overweight/obesity than
      same-aged youth from the general population. Even though dietary shifts are
      suspected, surprisingly little information exists concerning the dietary patterns
      of contemporary Native American adolescents. AIM: This study examines the dietary
      composition of Native American adolescents residing in upstate New York at the
      Akwesasne Mohawk Nation. The goal of this investigation is to assess the food
      patterns of Akwesasne adolescents via a total diet approach. PARTICIPANTS/SETTING
      AND METHODS: The sample is comprised of 246 Mohawk adolescents between the ages
      of 10-16.9 years of age residing at the Akwesasne Mohawk Nation. Food frequency
      data was collected from adolescents via interview during a cross-sectional study
      investigating their exposure to environmental pollutants. RESULTS AND CONCLUSION:
      Nutrient-dilute but energy-dense foods characterize most of the top 10 dietary
      sources of energy, carbohydrates, and fat. Although micronutrient intakes are by
      and large adequate in the sample, micronutrients are most often derived from
      highly fortified food sources. Adolescent diets contain few naturally-occurring
      sources of many micronutrients, especially folate and iron. A narrow variety of
      foods dominate the top dietary sources across both macronutrient and
      micronutrients, strongly suggesting the need for increased dietary diversity
      within this age group.

PMID- 24295082
TI  - Help(less): An Autoethnography About Caring for My Mother With Terminal Cancer.
AB  -  

PMID- 24295081
TI  - Acidolysis of p-coumaric acid with omega-3 oils and antioxidant activity of
      phenolipid products in in vitro and biological model systems.
AB  - Lipase-catalyzed acidolysis of p-coumaric acid with seal blubber oil (SBO) and
      menhaden oil (MHO) was carried out, followed by identification of major
      phenolipids in the resultant acidolysis mixture using high-performance liquid
      chromatography/mass spectrometry. Separation of phenolipid components from the
      resultant acidolysis mixture was achieved using flash column chromatography. The
      antioxidant activities of the phenolipids were examined in in vitro assays and
      biological model systems. The major phenolipids identified from acidolysis
      mixtures with both SBO and MHO included eight phenolic monoacylglycerols and
      eight phenolic diacylglycerols. Phenolipids derived from SBO and MHO generally
      showed good antioxidant potential in the systems tested. The prepared phenolipids
      exhibited high scavenging capacity toward 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      and peroxyl radicals and displayed reducing power, strong inhibitory effect on
      bleaching of beta-carotene, human low-density lipoprotein (LDL) cholesterol
      oxidation, as well as radical-induced DNA cleavage, thus suggesting that
      phenolipids derived from omega-3 oils may be used as potential stable products
      for health promotion and disease risk reduction. 

PMID- 24295083
TI  - Oxidation of flame retardant tetrabromobisphenol a by aqueous permanganate:
      reaction kinetics, brominated products, and pathways.
AB  - In this work, the most widely used brominated flame retardant tetrabromobisphenol
      A (TBrBPA) was shown to exhibit appreciable reactivity toward potassium
      permanganate [Mn(VII)] in water over a wide pH range of 5-10 with the maxima of
      second-order rate constants (kMn(VII) = 15-700 M(-1) s(-1)) at pH near its pKa
      values (7.5/8.5). A novel precursor ion scan (PIS) approach using negative
      electrospray ionization-triple quadrupole mass spectrometry (ESI-QqQMS) was
      adopted and further optimized for fast selective detection of brominated
      oxidation products of TBrBPA by Mn(VII). By setting PIS of m/z 79 and 81, two
      major products (i.e., 4-(2-hydroxyisopropyl)-2,6-dibromophenol and 4-isopropylene
      2,6-dibromophenol) and five minor ones (including 2,6-dibromophenol, 2,6-dibromo
      1,4-benzoquinone, and three dimers) were detected and suggested with chemical
      structures from their product ion spectra and bromine isotope patterns. Reaction
      pathways mainly involving the initial one-electron oxidation of TBrBPA and
      subsequent release and further reactions of 2,6-dibromo-4-isopropylphenol
      carbocation intermediate were proposed. The effectiveness of Mn(VII) for
      treatment of TBrBPA in real waters was confirmed. It is important to better
      understand the reactivity and toxicity of primary brominated products before
      Mn(VII) can be applied for treatment of TBrBPA-contaminated wastewater and source
      water. 

PMID- 24295084
TI  - Underreporting of HIV transmission among men who have sex with men in the
      Ukraine.

PMID- 24295085
TI  - Use of indacaterol for the treatment of COPD: a pharmacokinetic evaluation.
AB  - INTRODUCTION: Indacaterol is a beta2-agonist with a rapid onset of action and a
      bronchodilating effect that lasts for 24 h. AREAS COVERED: This review considers
      indacaterol in chronic obstructive pulmonary disease patients, in whom it is
      rapidly absorbed into the systemic circulation with serum levels measurable after
      5 min and Cmax being reached approximately 15 min post-dose. Its disposition
      kinetics are characterized by at least two phases, a relatively fast decline of
      the concentrations within the first 12 h, followed by a terminal elimination
      phase. The increase in systemic exposure is dose-proportional, but systemic
      concentrations are low at the recommended doses. Indacaterol is relatively highly
      bound to plasma proteins regardless of concentration. Metabolic clearance and/or
      biliary clearance account for the majority of its systemic excretion. Weight,
      age, gender and ethnicity significantly influence its pharmacokinetic profile,
      but it is not necessary to adjust the dose based on these covariates. Substrates,
      inhibitors or inducers of UGT1A1 and CYP3A may also affect the pharmacokinetic
      profile of indacaterol. EXPERT OPINION: Blood concentrations of indacaterol are
      unable to predict its bronchodilator effects. Furthermore, at the recommended
      doses, systemic concentrations of indacaterol are low and this is the likely
      reason for its safe profile.

PMID- 24295086
TI  - Characterization of a Nagina22 rice mutant for heat tolerance and mapping of
      yield traits.
AB  - BACKGROUND: Heat is one of the major factors that considerably limit rice
      production. Nagina 22 (N22) is a deep-rooted, drought and heat tolerant aus rice
      cultivar. This study reports the characterization of a previously isolated dark
      green leaf mutant N22-H-dgl219 (NH219) which showed reduced accumulation of
      reactive oxygen species in leaf under 40 degrees C heat conditions.The mutant was
      characterized for several traits in field under ambient (38 degrees C) and heat
      stress (44 degrees C) conditions by raising temperature artificially from
      flowering stage till maturity by covering plants with polythene sheets during dry
      season 2011. Yield traits were mapped in 70 F2 segregants of IR64 * NH219 and 36
      F2 segregants of its reciprocal cross. RESULTS: Leaf proteome analysis using two
      dimensional gel electrophoresis from N22 and NH219 showed distinct constitutive
      expression of ribulose bisphosphate carboxylase large chain precursor (EC
      4.1.1.39) in NH219 under ambient growth condition. Heat stress resulted in
      reduction of all 11 traits except plant height in both N22 and NH219. The extent
      of reduction was more in N22 than in NH219. Both pollen viability and spikelet
      fertility were not reduced significantly in N22 and NH219 but reduced by 20% in
      IR64. CONCLUSION: NH219 is more tolerant to heat stress than wild type N22 as its
      percent yield reduction is lesser than N22. Single marker analysis showed
      significant association of RM1089 with number of tillers and yield per plant,
      RM423 with leaf senescence, RM584 with leaf width and RM229 with yield per plant.

PMID- 24295087
TI  - Dibenzoyl and isoflavonoid glycosides from Sophora flavescens: inhibition of the
      cytotoxic effect of D-galactosamine on human hepatocyte HL-7702.
AB  - Twelve new dibenzoyl derivatives sophodibenzoside A-L (1-12) and five new
      isoflavone glycosides (13-17) have been isolated from the roots of Sophora
      flavescens together with eight known compounds (18-25). Notably, the use of
      acetic acid-d4 was required to enable identification of the dibenzoyl glycoside
      structures. Compounds 1, 2, 13, 14, and 19 exhibited weak inhibition of the
      cytotoxic effect of d-galactosamine on the human hepatic cell line HL-7702. 

PMID- 24295088
TI  - Prevalence, tumorigenic role, and biochemical implications of rare BRAF
      alterations.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant tumor
      of the thyroid gland, accounting for 74-80% of all thyroid cancers. The 1799T>A
      transversion is an activating mutation of the BRAF oncogene that is common in and
      specific to conventional PTC. We studied the prevalence, tumorigenic role, and
      biochemical implications of rare BRAF variants in a large cohort of patients.
      METHODS: A total of 2131 fine-needle aspiration biopsy samples were collected and
      subjected to BRAF mutation analysis. BRAF genetic variants were analyzed by
      Western blot, immunofluorescence, and in silico analysis. RESULTS: BRAF mutations
      were found in 50% (347/700) of thyroid cancers (644 PTCs, 22 anaplastic thyroid
      carcinomas, 34 follicular thyroid carcinomas). They were the classic (c.1799T>A,
      p.V600E) mutation in 96.8% (336/347) and rare genetic variants in 3.2% (11/347).
      In all, five infrequent BRAF alterations were detected: (i) c.1795_1797dupACA
      (p.T599dup); (ii) c.1801A>G (p.K601E); (iii) c.1799_1801delTGA (p.V600_K601>E);
      (iv) c.1799_1814>A (p.V600_S605>D); and (v) c.1798_1810delinsA (p.V600_W604>R).
      The last BRAF variant has never been described in the literature. Western blot
      analysis and immunofluorescence both revealed a variegated reactivity pattern,
      again emphasizing the peculiar role of every specific BRAF genetic alteration. In
      silico analysis of the samples studied revealed a stabilization of the "active"
      geometrical conformation of the B-raf enzyme associated with the activated and
      productive state of the kinase domain. CONCLUSIONS: Rare BRAF variants were found
      in 1.6% of all thyroid malignancies, all clustered around the codon V600, in the
      binding pocket named A-loop, confirming its crucial role in the enzymatic
      activation of the B-Raf protein. These mutations were associated mainly with the
      activation of key effectors in the mitogen-activated protein kinase pathway, but
      a simultaneous stimulation of the PI3k/Akt cascade was demonstrated in some
      cases. The rare BRAF variants were not generally associated with an aggressive
      behavior of the PTC. To our knowledge, this is the largest series of thyroid
      cancers analyzed to identify and functionally characterize rare BRAF variants.

PMID- 24295089
TI  - Preparation and characterizations of bioglass ceramic cement/Ca-P coating on pure
      magnesium for biomedical applications.
AB  - Magnesium has been recently recognized as a biodegradable metal for bone
      substitute applications. In order to improve the biocompatibility and
      osteointegration of pure Mg, two kinds of coatings, i.e., the Ca-P coating and
      bioglass ceramic cement (BGCC)/Ca-P coating, were prepared on the pure Mg ribbons
      in the present work. The Ca-P coating was obtained by aqueous solution method.
      Subsequently, Ca-P coated Mg was immersed into the BGCC slurry, which was
      prepared by the mix of SiO2-CaO-P2O5 bioglass ceramic (BGC) powders and phosphate
      liquid with a liquid-to-solid ratio (L/S) of 1.6, to obtain BGCC/Ca-P coating by
      a dipping-pulling method. The microstructures, morphologies, and compositions of
      these coatings have been characterized by X-ray diffraction (XRD) and scanning
      electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). The effect
      of these coatings on the mineralization activity of pure Mg has been
      investigated. The results indicated that both the Ca-P coating and BGCC/Ca-P
      coating could promote the nucleation of osteoconductive minerals, i.e., bone-like
      apatite, and the hydroxyapatite (HA) layer formed on the surface of the BGCC/Ca-P
      coating is obviously more dense, thick, and stable than that formed on the Ca-P
      coating after immersion in SBF solution for 15 days. The potentiodynamic
      polarization test indicated that the corrosion current density of the BGCC/Ca-P
      coated Mg is obviously lower than that of the Ca-P coating and 10 times lower
      than that of uncoated Mg. These results demonstrated that the BGCC/Ca-P coating
      can increase significantly the corrosion resistance of Mg and introduce a high
      biocompatibility of the bone-Mg substrate interface. In summary, the newly
      developed BGCC/Ca-P coated Mg has a good potential for biomedical applications. 

PMID- 24295092
TI  - Editor's introduction.

PMID- 24295091
TI  - New virtual case-based assessment method for decision making in undergraduate
      students: a scale development and validation.
AB  - BACKGROUND: There are many Internet forums where patients can ask medical
      question and get an answer from doctors. The aim of this study was to develop and
      validate the rating scale for the assessment of decision-making skills in
      undergraduate medical students based on such Internet questions. METHODS: This
      cross-sectional observational study carried out in Medical School of University
      of Maribor in Slovenia during the family medicine teaching course in the fourth
      study year. The sample consisted of 159 students. The source of data were the
      scoring sheets of the students' reports, assesses by two independent researchers.
      The assessment tool consisted of 10 items on a five-point Likert scale. RESULTS:
      Our final sample consisted of 147 (92.5%) students' reports. The ICC for matching
      of the final total scores on assessment tool of both assessors was 0.742.
      Cronbach's alpha of the assessment scale was 0.848. Factor analysis revealed four
      factors: initial assessment, physical examination planning, planning patient
      management and patient education/involvement. CONCLUSIONS: This assessment tool
      can be used for assessing undergraduate students' decision-making based on
      medical questions asked by real patients in a virtual setting.

PMID- 24295090
TI  - Expression of inflammation-related genes is associated with adipose tissue
      location in horses.
AB  - BACKGROUND: In humans, adipose tissue (AT) originating from different depots
      shows varying gene expression profiles. In horses, the risk of certain metabolic
      disorders may also be influenced by the impact of specific AT depots. Macrophage
      infiltration in human and rat AT is considered to be a source of inflammatory
      changes. In horses, this relationship has not been extensively studied yet.
      Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR),
      a useful method to evaluate differences in mRNA expression across different
      tissues, can be used to evaluate differences between equine AT depots. For a
      correct interpretation of the RT-qPCR results, expression data have to be
      normalized by the use of validated reference genes. The main objectives of this
      study were to compare mRNA expression of inflammation-related genes, as well as
      adipocyte morphology and number between different equine AT depots; and in
      addition, to investigate the presence of antigen presenting cells in equine AT
      and any potential relationship with adipokine mRNA expression. RESULTS: In this
      study, the mRNA expression of inflammation-related genes (leptin, chemokine
      ligand 5, interleukin 1beta, interleukin 6, interleukin 10, adiponectin, matrix
      metalloproteinase 2, and superoxide dismutase 2) and candidate reference gene
      stability was investigated in 8 different AT depots collected from the nuchal,
      abdominal (mesenteric, retroperitoneal, and peri-renal) and subcutaneous (tail
      head and loin) AT region. By using GeNorm analysis, HPRT1, RPL32, and GAPDH were
      found to be the most stable genes in equine AT. The mRNA expression of leptin,
      chemokine ligand 5, interleukin 10, interleukin 1beta, adiponectin, and matrix
      metalloproteinase 2 significantly differed across AT depots (P < 0.05). No
      significant AT depot effect was found for interleukin 6 and superoxide dismutase
      2 (P > 0.05). Adipocyte area and number of antigen presenting cells per adipocyte
      significantly differed between AT depots (P < 0.05). CONCLUSIONS: Adipose tissue
      location was associated with differences in mRNA expression of inflammation
      related genes. This depot-specific difference in mRNA expression suggests that
      the overall inflammatory status of horses could be partially determined by the
      relative proportion of the different AT depots.

PMID- 24295093
TI  - Contributing cause of death: poverty.

PMID- 24295095
TI  - Married to a memory: undetected grief in an assisted living environment.

PMID- 24295096
TI  - Hospice caregiver depression: the evidence surrounding the greatest pain of all.
AB  - Terminal illness affects the entire family, both the one with the illness and
      their loved ones. These loved ones must deal not only with the loss but with the
      challenges of managing daily care. The purpose of the systematic review of the
      peer-reviewed literature was to identify and explore depression and related
      interventions for caregivers of hospice patients. While the prevalence of
      depression reported in the identified studies of hospice caregivers ranges from
      26-57%, few interventions specific to this population have been tested and the
      research methods have been only moderately rigorous. 

PMID- 24295097
TI  - Living in liminality--being simultaneously visible and invisible: caregivers'
      narratives of palliative care.
AB  - Palliative care is an integral part of care and takes place in many settings-
      including the home, special accommodations, and hospitals. However, research
      shows that palliative care often ends with a death in the hospital due to the
      heavy burden on the primary caregiver. This study explores the meaning of being
      the primary caregiver of a close one who is terminally ill and is based on
      qualitative interviews with six primary caregivers of a terminally ill individual
      at home. The findings are discussed in the light of the theoretical concepts of
      liminality, lived body, and power. A potential impending risk exists of being
      abandoned when one is the primary caregiver to a close one who is terminally ill.
      This situation calls for professional caregivers to take responsibility and to
      respond to these, often unspoken, needs. This is particularly important
      concerning bodily care and the medical treatment regimen. In addition, when
      friends and relatives are absent, there is an ethical demand on professional
      caregivers to compensate for this lack and to compensate for this need.
      Palliative home care demands care that is person-centered--including the
      individual's history, family and loved ones, and individual strengths and
      weaknesses.

PMID- 24295098
TI  - The importance of place and time in translating knowledge about Canada's
      Compassionate Care Benefit to informal caregivers.
AB  - Canada's Compassionate Care Benefit (CCB), an employment insurance program
      designed to allow Canadian workers time off to care for a dying relative or
      friend, has had low uptake since its inception. Due to their role in working with
      family caregivers, social workers are one group of primary health care
      professionals who have been identified as benefiting from a knowledge translation
      campaign. Knowledge tools about the CCB have been developed through social worker
      input in a prior study. This article presents the findings of a qualitative
      exploratory intervention. Social workers (n = 8) utilized the tools for 6 months
      and discussed their experiences with them. Data analysis revealed references to
      time and space constraints in using to the tools, and demonstrated the impact of
      time geography on knowledge translation about the CCB. The results suggest that
      knowledge translation about the CCB could be targeted toward caregivers earlier
      on in the disease progression before the terminal diagnosis, and knowledge tools
      must be disseminated to more locations. These results may be valuable to
      policymakers and palliative care providers, as well as theorists interested in
      ongoing applications of time geography in knowledge translation and the
      consumption/production of care. 

PMID- 24295099
TI  - Social workers' roles in addressing the complex end-of-life care needs of elders
      with advanced chronic disease.
AB  - This study examined social workers' roles in caring for low-income elders with
      advanced chronic disease in an innovative, community-based managed care program,
      from the perspective of elders, family, team members, and social workers. The
      results are drawn from a larger longitudinal, multimethod case study. Sources of
      data include survey reports of needs addressed by social workers for 120 deceased
      elders, five focus groups with interdisciplinary team members, and in-depth
      interviews with 14 elders and 10 of their family caregivers. A thematic
      conceptual matrix was developed to detail 32 distinctive social work roles that
      address divergent needs of elders, family, and team members. Distinctive
      perceptions of social workers' roles were identified for the different
      stakeholder groups (i.e., elders, family caregivers, team members, and social
      workers). Findings from this study may inform supervisors and educators regarding
      training needs of those preparing to enter the rapidly growing workforce of
      gerontological social workers who may be called upon to care for elders at the
      end of life. Training is particularly warranted to help social workers gain the
      skills needed to more successfully treat symptom management, depression, anxiety,
      agitation, grief, funeral planning, and spiritual needs that are common to the
      end of life. 

PMID- 24295100
TI  - Working with Russian-Jewish immigrants in end-of-life care settings.
AB  - This article examines Russian-Jewish immigrant clients' attitudes toward death
      and dying in the context of today's health care system. Aspects of individuals'
      collective past--such as the traumatic history of their country of origin;
      cultural prohibitions against discussing pain, suffering, and death; and the lack
      of familiarity with palliative care that are likely to affect their decisions
      about end-of-life care--are discussed. Case vignettes are provided, with a
      discussion on how best to engage these clients in therapeutic work.

PMID- 24295101
TI  - Community systems strengthening for HIV care: experiences from Uganda.
AB  - The growing HIV burden on families and health systems is exerting a shift toward
      community caregivers, and is increasing the demand for functional community
      systems. In Uganda, where the number of people with HIV is increasing against a
      background of weak health systems, the role of community systems is poorly
      understood. We investigated the role of community systems in palliative care and
      the system elements required for an effective community response in Uganda.
      Qualitative interviews and focus group discussions were conducted among providers
      and recipients of palliative care, their family members, and governmental and
      community stakeholders in Mbale and Jinja, Uganda. Results showed that community
      systems play an important role in many aspects of palliative care--including
      personal, livelihood, nutritional and bereavement support--and often strengthen
      care linkages and referrals. For community systems to fulfill these roles
      effectively, multiple system elements--including leadership, training,
      partnerships, and enabling policies--are essential. Strengthening community
      systems could be an effective strategy to alleviate HIV burden on families and
      health systems. A systems approach could be a potent mechanism for determining
      which community structures to strengthen in order to maximize the impact of
      palliative care programs, and for guiding investments in HIV and health.

PMID- 24295105
TI  - Surface water enhances the uptake and photoreactivity of gaseous catechol on
      solid iron(III) chloride.
AB  - Uptake and photoreactivity of catechol-Fe complexes are investigated at the
      gas/solid interface under humid and dry conditions, along with the nature of the
      hydrogen-bonding network of adsorbed water. Catechol was chosen as a simple model
      for organics in aerosols. Iron chloride was used to distinguish ionic mobility
      from binding to coordinated iron(III) in hematite. Studies were conducted using
      diffuse reflectance infrared Fourier transform spectroscopy as a function of
      irradiation time. Results show that adsorbed water at 30% relative humidity (RH),
      not light, increases the concentration of adsorbed catechol by a factor of 3 over
      60 min relative to dry conditions. Also, our data show that, at 30% RH and under
      light and dark conditions, growth factors describing the concentration of
      adsorbed catechol are very similar suggesting that light does not significantly
      enhance the uptake of catechol vapor on FeCl3. Surface water also enhances the
      initial photodecay kinetics of catechol-Fe complexes at 30% RH by a factor of 10
      relative to control experiments (RH < 1%, or no FeCl3 under humid conditions).
      Absorptions assigned to carbonyl groups were not observed with irradiation time,
      which was explained by the dominance of FeCl(2+) species relative to FeOH(2+) in
      the highly acidic "quasi-liquid" phase at 30% RH. Clear differences in the
      hydrogen-bonding network upon gaseous catechol uptake are observed in the dark
      and light and during the photodecay of adsorbed catechol. The implications of
      these results on our understanding of interfacial processes in aged iron
      containing surfaces are discussed. 

PMID- 24295106
TI  - Comparative N-glycan profiling of colorectal cancer cell lines reveals unique
      bisecting GlcNAc and alpha-2,3-linked sialic acid determinants are associated
      with membrane proteins of the more metastatic/aggressive cell lines.
AB  - Advances in colorectal cancer (CRC) diagnosis will be enhanced by development of
      more sensitive and reliable methods for early detection of the disease when
      treatment is more effective. Because many known disease biomarkers are membrane
      bound glycoproteins with important biological functions, we chose to compare N
      glycan profiles of membrane proteins from three phenotypically different CRC cell
      lines, LIM1215, LIM1899, and LIM2405, representing moderately differentiated
      metastatic, moderately differentiated primary, and poorly differentiated
      (aggressive) primary CRC cell lines, respectively. The N-glycan structures and
      their relative abundances were determined as their underivatized reduced forms,
      using porous graphitized carbon LC-ESI-MS/MS. A key observation was the similar N
      glycan landscape in these cells with the dominance of high mannose type glycan
      structures (70-90%) in all three cell lines, suggesting an incomplete glycan
      processing. Importantly, unique glycan determinants such as bisecting N
      acetylglucosamine were observed at a high level in the metastatic LIM1215 cells,
      with some expressed in the moderately differentiated LIM1899, while none were
      detected in the poorly differentiated LIM2405 cells. Conversely, alpha-2,3
      sialylation was completely absent in LIM1215 and LIM1899 and present only in
      LIM2405. RNA-Seq and lectin immunofluorescence data correlated well with these
      data, showing the highest upregulation of Mgat3 and binding with PHA-E in
      LIM1215. Downregulation of Man1alpha1 and Mgat1 in LIM1215 also coincided with
      the higher degree of incomplete N-glycan processing and accumulation of high
      mannose type structures as well as bisecting N-glycans when compared to the other
      two cell lines. This study provides a comprehensive analysis of the membrane N
      glycome in three CRC cell lines and identifies N-glycosylation differences that
      correlate with the histological and pathological features of the cell lines. The
      unique glycosylation phenotypes may therefore serve as a molecular feature to
      differentiate CRC disease stages. 

PMID- 24295107
TI  - The properties research of polymerized human placenta hemoglobin before and after
      lyophilization.
AB  - In this study, lyophilization was applied to polymerized human placenta
      hemoglobin (PolyPHb) solution. The lyophilization process was carried out with
      freezing at - 70 degrees C for 5 h and two phases of drying: the first phase of
      drying was carried out at -35 degrees C-35 degrees C for 16 h and the second
      phase at 35 degrees C for 8 h. Hemoglobin (Hb) concentration, methemoglobin
      (MetHb) content, oxygen-carrying capacity, Fe(3+) content, pH, UV spectrum,
      average molecular weight and its distribution, circular dichroism, SDS-PAGE, P50,
      crystal osmotic pressure, colloid osmotic pressure, zeta potential, average
      particle size, and other indicators were measured before and after
      lyophilization. Residual water content and rehydration time of the lyophilized
      products were also evaluated. All the indicators of lyophilized samples showed
      that the physical and biochemical properties of PolyPHb are not markedly changed
      before and after lyophilization. In this light, lyophilization may be a promising
      method for the preservation of PolyPHb solution.

PMID- 24295108
TI  - Effects of wearing high heels on the forefoot: an MRI evaluation.

PMID- 24295109
TI  - Health care and social media platforms in hospitals.
AB  - The objective of this article is to illustrate user characteristics of a
      hospital's social media structure using analytics and user surveys. A 1-year
      retrospective analysis was conducted along with an Internet survey of users of
      the hospital's Facebook, Twitter, and blog. Of the survey respondents (n = 163),
      95.7% are female and 4.3% are male; most are ages 50-59 years (31.5%) and 40-49
      years (27.8%); and 93.2% are Caucasian. However, the hospital system database
      revealed 55% female and 37% minority population, respectively. Of the survey
      respondents, 61.4% reported having a bachelor's degree or higher, whereas only
      11.7% reported having a high school degree/equivalent or lower. However, within
      the hospital patient databases, 93% of patients have a high school
      degree/equivalent or lower and only 3% have a bachelor's degree or higher in our
      women's services population. Social media were used to seek personal health
      information 68.7% (n = 112), to learn about hospital programming 27.6% (n = 45),
      and to seek family health information 25.2% (n = 41). Respondents younger than 49
      years of age were more likely to seek personal health information using social
      media compared to those 50 years of age and older (p = .02). Respondents with a
      bachelor's degree or higher education were statistically less likely to search
      for physician information compared to those less educated individuals (p = .04).
      We conclude that social media may play an important role in personal health
      information, especially for young female respondents; however, the survey
      provides strong evidence that further research is needed to ensure that social
      network sites provided by hospitals are reaching the full spectrum of health
      system patients. 

PMID- 24295111
TI  - Automation in the bioanalytical laboratory: what is the future?

PMID- 24295110
TI  - Base-excision repair activity of uracil-DNA glycosylase monitored using the latch
      zone of alpha-hemolysin.
AB  - Nanopores have been investigated as a simple and label-free tool to characterize
      DNA nucleotides when a ssDNA strand translocates through the constriction of the
      pore. Here, a wild-type alpha-hemolysin protein nanopore was used to monitor DNA
      repair enzyme activity based on base-specific interactions of dsDNA with the
      vestibule constriction "latch", a previously unrecognized sensing zone in alpha
      hemolysin specific for dsDNA structure. The presence of a single abasic site
      within dsDNA that is in proximity to the latch zone (+/-2 nucleotides) results in
      a large increase in ion channel current, allowing accurate quantitation of the
      kinetics of base repair reactions involving an abasic site product. Taking
      advantage of the high resolution for abasic site recognition, the rate of uracil
      DNA glycosylase hydrolysis of the N-glycosidic bond, converting 2'-deoxyuridine
      in DNA to an abasic site, was continuously monitored by electrophoretically
      capturing reaction substrate or product dsDNA in the ion channel vestibule. Our
      work suggests use of the nanopore as an enzymology tool and provides a means to
      identify single base structural changes in dsDNA. 

PMID- 24295112
TI  - Using phosphoproteomics to monitor disregulated signaling networks in cardiac
      disease preceding heart failure.

PMID- 24295113
TI  - Data processing for 2D-LC: where are we heading?

PMID- 24295115
TI  - ICP-MS in drug development: high-throughput analysis of strontium and calcium in
      bone, tissue and plasma.
AB  - BACKGROUND: The high-throughput analysis of strontium and calcium in plasma,
      tissue and bone (femur) using inductively coupled plasma-MS is described. Method
      validation, the results and experience obtained during sample analysis are
      highlighted. RESULTS: The different matrices were destructed with concentrated
      nitric acid by heating at 60 degrees C overnight. Using this approach it was
      possible to analyze large numbers of samples in parallel. CONCLUSION: Inductively
      coupled plasma-MS proved to be a highly sensitive, robust and efficient technique
      for the analysis of several different biological samples. A total of 6767 samples
      were analyzed, and the performance of the method was illustrated by the fact that
      only 0.2% of the samples had to be reanalyzed due to anomalous results and ISR
      for all matrices fulfilled the acceptance criteria.

PMID- 24295116
TI  - Rugged and accurate quantitation of colchicine in human plasma to support
      colchicine poisoning monitoring by using turbulent-flow LC-MS/MS analysis.
AB  - BACKGROUND: Colchicine is a common drug used in inflammatory diseases. The narrow
      therapeutic index requires fast and reliable techniques for its quantitation. An
      online, automated sample preparation using TurboFlowTM technology combined with
      triple-stage quadrupole MS detection was applied to identify colchicine in human
      plasma and follow intoxications. METHODOLOGY: Plasma samples (200 ul) were mixed
      with deuterated colchicine and protein precipitation ZnSO4 solutions. After
      centrifugation, supernatants were extracted onto a Cyclone P TurboFlow column and
      eluted onto a narrowbore HypersilTM GOLD column with a methanol/water gradient.
      Analytes were monitored in SRM mode (positive electrospray). RESULTS: Total run
      time was 9.5 min. Calibration curves ranged from 0.342 to 17.1 ng/ml, with
      significant linearity (R(2) >0.99). Inter- and intra-assay precisions were <16.8%
      and accuracy was 84.4-110%. CONCLUSION: This method is suitable for monitoring
      intoxication in patients undergoing chronic treatment and is routinely applied to
      toxicological samples.

PMID- 24295117
TI  - Is SPME a destination or just another station for bioanalysis?
AB  - This article reviews the solid-phase microextraction technique and its potential
      to revolutionize bioanalysis in terms of combining sampling, sample preparation
      and extraction in one step with no blood withdrawal. Possible hurdles facing the
      technology when implemented in a pharmaceutical setting will be covered and the
      author will provide an outlook on the future of solid-phase microextraction as a
      novel microsampling technique for bioanalysis. 

PMID- 24295118
TI  - Analytical assay platforms for soluble target engagement biomarkers: old
      favorites and emerging technologies.
AB  - Quantification of soluble biomarkers is critical for assessing target engagement
      in both preclinical and clinical settings. Since the advent of the commonly used
      ELISA, there has been an array of immunoassay platforms to achieve this goal, and
      many researchers will have a favorite. This review will compare and contrast
      immunoassay technologies used by many pharmaceutical and CRO groups and highlight
      emerging assay platforms that may deliver more sensitive assays. Several case
      studies will be used throughout as the changing immunoassay landscape is
      discussed. 

PMID- 24295119
TI  - Advances in the quantitation of therapeutic insulin analogues by LC-MS/MS.
AB  - Insulin analogues represent a major and growing class of biotherapeutics, and
      their quantitation is an important focus of commercial and public effort across a
      number of different fields. As LC-MS has developed, it has become an increasingly
      practicable and desirable alternative to ligand-binding-based approaches for
      quantitation of this class of compounds. The sensitivity challenge of measuring
      trace levels of this large peptide molecule in a protein-containing matrix is
      considerable; however, different approaches to detection, extraction and
      separation are described to overcome this challenge, including immunoaffinity
      capture, SPE and low-flow HPLC. Considerations such as bioanalytical assay
      acceptance criteria and antidrug antibody effects during drug development are
      included, alongside descriptions of recent sports doping and clinical
      applications. Factors affecting the correlation and agreement of MS with
      biological ligand-binding methods are discussed, with ways to anticipate and
      appreciate differences between the values derived from each technique. The
      'future perspective' section discusses the likely trend towards MS-based analysis
      for these compounds and the impact of HRMS. A high degree of scientific
      creativity, combined with science-defined regulatory approaches that define
      suitable validation criteria, will be needed to meet the demanding requirements
      for high-throughput analysis of insulin by LC-MS. 

PMID- 24295120
TI  - Recent advances in the bioanalysis of modified nucleotides in epigenetic studies.
AB  - Epigenetic alterations, such as DNA methylation, are involved in the pathogenesis
      of various diseases, the toxicity of diverse agents, the process of aging, the
      development of stem cells and numerous other mechanisms. DNA methylation is one
      of the most well-studied epigenetic alterations in mammals. Nevertheless, the
      scientific interest is now focusing on novel modified nucleotides with potential
      regulatory roles, such as 5-hydroxymethylcytosine. We currently present and
      discuss novel bioanalytical strategies developed for the determination of various
      modified nucleotides in epigenetic studies. 

PMID- 24295121
TI  - Sensitive glucagon quantification by immunochemical and LC-MS/MS methods.
AB  - The peptide hormone glucagon plays an important role in homeostasis of glucose
      concentrations in the blood. Its biological importance is evidenced through the
      conservation of its peptide sequence between species. Reliable assays for
      glucagon in biological samples are important for gaining a better understanding
      of the pathology and treatment of diabetes. Numerous assays are available for the
      analysis of glucagon in biological samples, the majority of which employ an
      immunochemical approach and have been available for many years. However, recent
      advances in MS instrumentation and the amenability of glucagon for analysis by LC
      MS/MS has brought these new methods to the forefront. Concentrations of glucagon
      determined from different methods are not always consistent and this review
      provides suggestions of how to improve the reliability of methods for glucagon
      analysis. 

PMID- 24295123
TI  - Attentional control, attentional network functioning, and emotion regulation
      styles.
AB  - Attentional network functioning in emotionally neutral conditions and self
      reported attentional control (AC) were analysed as predictors of the tendency to
      engage in dysfunctional emotion regulation strategies. Diminished attentional
      orienting predicted an increased tendency to engage in brooding rumination, and
      enhanced alertness predicted a greater chance of suppression, beyond trait
      anxiety and self-reported AC, which were not predictive of either rumination or
      suppression. This is the first study to show that some forms of dysfunctional
      emotion regulation are related to the attentional network functioning in
      emotionally neutral conditions. Results are discussed in relation to regulatory
      temperament and anxiety-related attentional biases literature. 

PMID- 24295124
TI  - The Manchester Uveitis Clinic: the first 3000 patients--epidemiology and casemix.
AB  - PURPOSE: To demonstrate the demography, anatomical, and diagnostic classification
      of patients with uveitis attending the Manchester Uveitis Clinic (MUC), a
      specialist uveitis clinic in the northwest of England, UK. METHODS: Retrospective
      retrieval of data on a computerized database incorporating all new referrals to
      MUC from 1991 to 2013. RESULTS: A total of 3000 new patients with uveitis were
      seen during a 22-year period. The anatomical types seen were anterior 46%;
      intermediate 11.1%; posterior 21.8%; and panuveitis 21.1%. The most common
      diagnoses were Fuchs heterochromic uveitis (11.5% of total), sarcoidosis-related
      uveitis (9.7%), idiopathic intermediate uveitis (7.9%), idiopathic acute anterior
      uveitis (7.0%), and toxoplasmosis (6.9%). Syphilis and tuberculosis-associated
      uveitis increased markedly in frequency during the study period. CONCLUSIONS: The
      uveitis casemix in this region reflects a predominantly white Caucasian
      population in a temperate country, but with changing characteristics owing to
      increasing immigration, enhanced diagnostic techniques, changes in referral
      pattern, and some real changes in disease incidence.

PMID- 24295125
TI  - N-Difluoromethylation of imidazoles and benzimidazoles using the Ruppert-Prakash
      reagent under neutral conditions.
AB  - Direct N-difluoromethylation of imidazoles and benzimidazoles has been achieved
      using TMS-CF3 (the Ruppert-Prakash reagent) under neutral conditions.
      Difluoromethylated products were obtained in good-to-excellent yields.
      Inexpensive, commercially available starting materials, neutral conditions, and
      shorter reaction times are advantages of this methodology. Reactions are
      accessible through conventional as well as microwave irradiation conditions. 

PMID- 24295126
TI  - Codendrimer from polyamidoamine (PAMAM) and oligoethylene dendron as a
      thermosensitive drug carrier.
AB  - The efficient synthesis of codendrimer PAMAM-co-OEG (PAG) and its properties in
      aqueous solution, including particle size and thermosensitivity, are described.
      PAG is synthesized with well-defined structure through the "attach to" route. In
      the aqueous solutions, PAG forms unimer and multimolecular aggregates with the
      respective particle sizes of approximately 8 and 200 nm, depending on the
      concentration. PAG shows thermosensitive behavior with sharp and fast transition,
      and the lower critical solution temperature is 38.2  degrees C. The suitability
      of codendrimer PAG as the thermosensitive carrier is evaluated with methotrexate
      (MTX) as the model drug. MTX is encapsulated in PAG with the drug-loading
      capacity of 39%, among which 30% of MTX is encapsulated in PAMAM core. The
      release behavior of MTX mediated by temperature is investigated with focus on the
      effects around the LCST of PAG. 

PMID- 24295127
TI  - Review of enzyme-linked immunosorbent assays (ELISAs) for analyses of
      neonicotinoid insecticides in agro-environments.
AB  - Immunoassay is a promising method that is suitable for rapid and simple analyses
      of pesticides, which are likely to persist at a trace level in agro-environments,
      including agricultural products, soil, and water. Particularly, enzyme-linked
      immunosorbent assay (ELISA) has wide application to development of analytical
      methods for pesticide residues because it can very sensitively and very
      accurately determine them in samples. This paper presents a review of the
      fundamental analytical performance, a device for the sample pretreatment methods
      before determination, and cases of applications to various samples on ELISA
      methods that have been developed for detection of neonicotinoid insecticides in
      food or environmental matrices. The reviewed ELISAs can be ranked as
      quantitative, rapid and simple analytical methods for single analytes. The
      recognition of ELISA as an analytical methodology for pesticide residues is
      expected to advance rapidly in the future. 

PMID- 24295128
TI  - Evolution and dynamics of megaplasmids with genome sizes larger than 100 kb in
      the Bacillus cereus group.
AB  - BACKGROUND: Plasmids play a crucial role in the evolution of bacterial genomes by
      mediating horizontal gene transfer. However, the origin and evolution of most
      plasmids remains unclear, especially for megaplasmids. Strains of the Bacillus
      cereus group contain up to 13 plasmids with genome sizes ranging from 2 kb to 600
      kb, and thus can be used to study plasmid dynamics and evolution. RESULTS: This
      work studied the origin and evolution of 31 B. cereus group megaplasmids (>100
      kb) focusing on the most conserved regions on plasmids, minireplicons. Sixty-five
      putative minireplicons were identified and classified to six types on the basis
      of proteins that are essential for replication. Twenty-nine of the 31
      megaplasmids contained two or more minireplicons. Phylogenetic analysis of the
      protein sequences showed that different minireplicons on the same megaplasmid
      have different evolutionary histories. Therefore, we speculated that these
      megaplasmids are the results of fusion of smaller plasmids. All plasmids of a
      bacterial strain must be compatible. In megaplasmids of the B. cereus group,
      individual minireplicons of different megaplasmids in the same strain belong to
      different types or subtypes. Thus, the subtypes of each minireplicon they contain
      may determine the incompatibilities of megaplasmids. A broader analysis of all
      1285 bacterial plasmids with putative known minireplicons whose complete genome
      sequences were available from GenBank revealed that 34% (443 plasmids) of the
      plasmids have two or more minireplicons. This indicates that plasmid fusion
      events are general among bacterial plasmids. CONCLUSIONS: Megaplasmids of B.
      cereus group are fusion of smaller plasmids, and the fusion of plasmids likely
      occurs frequently in the B. cereus group and in other bacterial taxa. Plasmid
      fusion may be one of the major mechanisms for formation of novel megaplasmids in
      the evolution of bacteria.

PMID- 24295129
TI  - Central review of lymphoma diagnosis: still a prerequisite for best patient care
      in 2014?

PMID- 24295130
TI  - The clinical features, management and prognosis of primary and secondary indolent
      lymphoma of the bone: a retrospective study of the International Extranodal
      Lymphoma Study Group (IELSG #14 study).
AB  - Indolent lymphomas primarily involving the skeleton (iPBL) represent < 1% of all
      primary bone lymphomas. The management and prognosis have not been previously
      described. Patients with primary and secondary iPBL were selected from an
      international database of 499 patients with a histopathological diagnosis of non
      Hodgkin lymphoma and skeleton involvement, and clinical features, management and
      prognosis were analyzed. Twenty-six (5%) patients had an iPBL. Ten patients had
      small lymphocytic lymphoma, 10 had follicular lymphoma and six had
      lymphoplasmacytic lymphoma. Eleven patients had limited stage and 15 had advanced
      disease. The overall response rate was 73% (95% confidence interval [CI] = 57
      89%). Median follow-up was 58 months, and the 5- and 10-year progression-free
      survival (PFS) rates were 37 +/- 10% and 25 +/- 12%, respectively. Nine patients
      are alive, with 5- and 10-year overall survival (OS) rates of 46 +/- 10% and 29
      +/- 11%, respectively. Patients with small lymphocytic lymphoma showed
      significantly better outcome than patients with follicular lymphoma. Performance
      status and stage of disease were independently associated with OS. The prognosis
      of patients with primary bone lymphoplasmacytic or follicular lymphoma was less
      favorable.

PMID- 24295131
TI  - Lenalidomide in patients with POEMS syndrome: a systematic review and pooled
      analysis.
AB  - The purpose of this pooled analysis was to synthesize all available data so as to
      evaluate the efficacy and safety of lenalidomide in patients with POEMS syndrome.
      Eligible articles were identified by a search in MEDLINE and ClinicalTrials.gov
      databases using a predefined combination. Eligible cases of patients treated in
      our department were additionally included. Overall, 51 patients were included.
      The median age of patients was 54.5 years (range: 32-79 years). Lenalidomide was
      given as first- or second-line treatment in 28.6% and 47.6% of patients,
      respectively. Hematological responses included complete response in 18.6%, very
      good partial response in 39.5% and partial response in 37.2% of cases. Vascular
      endothelial growth factor (VEGF) reduction was reported in all cases. Neuropathy
      improved in 92.0% of cases and stabilized in 8%. The progression-free survival
      (PFS) estimate at 12 months was 93.9%. Lenalidomide can represent a safe and
      effective option for the treatment of patients with POEMS.

PMID- 24295133
TI  - The problem with cyclophosphamide, doxorubicin, vincristine and prednisone for
      the treatment of peripheral T-cell lymphoma.

PMID- 24295134
TI  - Use of density functional theory in drug metabolism studies.
AB  - INTRODUCTION: The cytochrome P450 enzymes (CYPs) metabolize many drug compounds.
      They catalyze a wide variety of reactions, and potentially, a large number of
      different metabolites can be generated. Density functional theory (DFT) has, over
      the past decade, been shown to be a powerful tool to rationalize and predict the
      possible metabolites generated by the CYPs as well as other drug-metabolizing
      enzymes. AREAS COVERED: We review applications of DFT on reactions performed by
      the CYPs and other drug-metabolizing enzymes able to perform oxidation reactions,
      with an emphasis on predicting which metabolites are produced. We also cover
      calculations of binding energies for complexes in which the ligands interact
      directly with the heme iron atom. EXPERT OPINION: DFT is a useful tool for
      prediction of the site of metabolism. The use of small models of the enzymes work
      surprisingly well for most CYP isoforms. This is probably due to the fact that
      the binding of the substrates is not the major determinant. When binding of the
      substrate plays a significant role, the well-known issue of determining the free
      energy of binding is the challenge. How approaches taking the protein environment
      into account, like docking, MD and QM/MM, can be used are discussed.

PMID- 24295132
TI  - Targeting the apoptosis pathway in hematologic malignancies.
AB  - Apoptosis is a cell death program that is well-orchestrated for normal tissue
      homeostasis and for removal of damaged, old or infected cells. It is regulated by
      intrinsic and extrinsic pathways. The intrinsic pathway responds to signals such
      as ultraviolet radiation or DNA damage and activates "executioner" caspases
      through a mitochondria-dependent pathway. The extrinsic pathway is activated by
      death signals induced, for example, by an infection that activates the immune
      system or receptor-mediated pathways. The extrinsic pathway signals also cascade
      down to executioner caspases that cleave target proteins and lead to cell death.
      Strict control of cellular apoptosis is important for the hematopoietic system as
      it has a high turnover rate. However, the apoptosis program is often deregulated
      in hematologic malignancies leading to the accumulation of malignant cells.
      Therefore, apoptosis pathways have been identified for the development of
      anticancer therapeutics. We review here the proteins that have been targeted for
      anticancer drug development in hematologic malignancies. These include BCL-2
      family proteins, death ligands and receptors, inhibitor of apoptosis family
      proteins and caspases. Except for caspase activators, drugs that target each of
      these classes of proteins have advanced into clinical trials.

PMID- 24295135
TI  - Recent developments in the catalytic, asymmetric construction of pyrroloindolines
      bearing all-carbon quaternary stereocenters.
AB  - Pyrroloindoline alkaloids constitute a large family of natural products that has
      inspired the development of an impressive array of new reactions to prepare the
      key heterocyclic motif. This synopsis will address catalytic, asymmetric
      reactions developed to synthesize pyrroloindolines bearing C3a all-carbon
      quaternary stereocenters. The methods described herein include both transition
      metal-catalyzed and organocatalyzed reactions that have been demonstrated to be
      suitable for the synthesis of the pyrroloindoline framework. 

PMID- 24295136
TI  - Toward proof of concept of a one health approach to disease prediction and
      control.
AB  - A One Health approach considers the role of changing environments with regard to
      infectious and chronic disease risks affecting humans and nonhuman animals.
      Recent disease emergence events have lent support to a One Health approach. In
      2010, the Stone Mountain Working Group on One Health Proof of Concept assembled
      and evaluated the evidence regarding proof of concept of the One Health approach
      to disease prediction and control. Aspects examined included the feasibility of
      integrating human, animal, and environmental health and whether such integration
      could improve disease prediction and control efforts. They found evidence to
      support each of these concepts but also identified the need for greater
      incorporation of environmental and ecosystem factors into disease assessments and
      interventions. The findings of the Working Group argue for larger controlled
      studies to evaluate the comparative effectiveness of the One Health approach. 

PMID- 24295137
TI  - Ontology of physics for biology: representing physical dependencies as a basis
      for biological processes.
AB  - BACKGROUND: In prior work, we presented the Ontology of Physics for Biology (OPB)
      as a computational ontology for use in the annotation and representations of
      biophysical knowledge encoded in repositories of physics-based biosimulation
      models. We introduced OPB:Physical entity and OPB:Physical property classes that
      extend available spatiotemporal representations of physical entities and
      processes to explicitly represent the thermodynamics and dynamics of
      physiological processes. Our utilitarian, long-term aim is to develop
      computational tools for creating and querying formalized physiological knowledge
      for use by multiscale "physiome" projects such as the EU's Virtual Physiological
      Human (VPH) and NIH's Virtual Physiological Rat (VPR). RESULTS: Here we describe
      the OPB:Physical dependency taxonomy of classes that represent of the laws of
      classical physics that are the "rules" by which physical properties of physical
      entities change during occurrences of physical processes. For example, the fluid
      analog of Ohm's law (as for electric currents) is used to describe how a blood
      flow rate depends on a blood pressure gradient. Hooke's law (as in elastic
      deformations of springs) is used to describe how an increase in vascular volume
      increases blood pressure. We classify such dependencies according to the flow,
      transformation, and storage of thermodynamic energy that occurs during processes
      governed by the dependencies. CONCLUSIONS: We have developed the OPB and
      annotation methods to represent the meaning-the biophysical semantics-of the
      mathematical statements of physiological analysis and the biophysical content of
      models and datasets. Here we describe and discuss our approach to an ontological
      representation of physical laws (as dependencies) and properties as encoded for
      the mathematical analysis of biophysical processes.

PMID- 24295138
TI  - Water-based, nonfluorinated dispersions for environmentally benign, large-area,
      superhydrophobic coatings.
AB  - Low-cost, large-area, superhydrophobic coating treatments are of high value to
      technological applications requiring efficient liquid repellency. While many
      applications are envisioned, only few are realizable in practice due to either
      the high cost or low durability of such treatments. Recently, spray deposition of
      polymer-particle dispersions has been demonstrated as an excellent means for
      producing low-cost, large-area, durable, superhydrophobic composite
      coatings/films; however, such dispersions generally contain harsh or volatile
      solvents, which are required for solution processing of polymers as well as for
      dispersing hydrophobic nanoparticles, thus inhibiting scalability due to the
      increased cost in chemical handling and environmental safety concerns. Moreover,
      such coatings usually contain fluoropolymers due to their inherent low surface
      energy, a requirement for superhydrophobicity, but concerns over their
      biopersistence has provided an impetus for eliminating these chemicals. For spray
      coating, the former problem can be overcome by replacing organic solvents with
      water, but this situation seems paradoxical: Producing a highly water-repellent
      coating from an aqueous dispersion. We report a water-based, nonfluorinated
      dispersion for the formation of superhydrophobic composite coatings applied by
      spray on a variety of substrates. We stabilize hydrophobic components (i.e.,
      polymer, nanoparticles) in water, by utilizing chemicals containing acid
      functional groups (i.e., acrylic acid) that can become ionized in aqueous
      environments under proper pH control (pH > 7). The functional polymer utilized in
      this study is a copolymer of ethylene and acrylic acid, while the particle filler
      is exfoliated graphite nanoplatelet (xGnP), which contains functional groups at
      its periphery. Once spray deposited and dried, the components become insoluble in
      water, thus promoting liquid repellency. Such coatings can find a wide range of
      applications due to their benign processing nature as well as the variety of
      substrates on which they can be deposited. 

PMID- 24295140
TI  - Fourth-order perturbative model for photoinduced internal conversion processes.
AB  - Essential to the functionality of numerous biological and synthetic molecular
      systems is the ability to rapidly convert electronic excitation energy into heat.
      Such internal conversion (IC) transitions often cannot be described by
      traditional second-order kinetic theories because of time-coincident electronic
      and nuclear relaxation processes. Here, we present a perturbative fourth-order
      phenomenological model for photoinduced IC that incorporates effects associated
      with finite laser bandwidths and nonequilibrium nuclear motions. Specialized
      knowledge of first-principles computational methods is not required, and many
      parameters can be obtained with standard spectroscopic measurements. The model is
      applied to the IC processes that precede electrocyclic ring-opening in alpha
      terpinene. It is shown that the primary factor governing the shape of the
      population decay profile (Gaussian versus exponential) is the rate at which the
      wavepacket approaches the geometry corresponding to degeneracy between the
      excited states. Other parameters such as the displacement in the promoting mode
      and the thermal fluctuation amplitudes affect the sensitivity of the IC dynamics
      to motion of the wavepacket but do not alter the basic physical picture. Finally,
      we suggest a wavepacket representation of the IC process to visualize
      correlations between population-transfer dynamics and the amount of energy
      transferred from the system to the bath. 

PMID- 24295139
TI  - Inhibition of heat-induced apoptosis in rat small intestine and IEC-6 cells
      through the AKT signaling pathway.
AB  - BACKGROUND: As the world warms up, heat stress is becoming a major cause of
      economic loss in the livestock industry. Long-time exposure of animals to
      hyperthermia causes extensive cell apoptosis, which is harmful to them. AKT and
      AKT-related serine-threonine kinases are known to be involved in signaling
      cascades that regulate cell survival, but the mechanism remains elusive. In the
      present study, we demonstrate that phosphoinositide 3-kinase (PI3K) /AKT signal
      pathway provides protection against apoptosis induced by heat stress to ascertain
      the key point for treatment. RESULTS: Under heat stress, rats showed increased
      shedding of intestinal epithelial cells. These rats also had elevated levels of
      serum cortisol and improved expression of heat shock proteins (Hsp27, Hsp70 and
      Hsp90) in response to heat stress. Apoptosis analysis by TUNEL assay revealed a
      higher number of villi epithelial cells that were undergoing apoptosis in heat
      treated rats than in the normal control. This is supported by gene expression
      analysis, which showed an increased ratio of Bax/Bcl-2 (p < 0.05), an important
      indicator of apoptosis. During heat-induced apoptosis, more AKTs were activated,
      showing increased phosphorylation. An increase of BAD phosphorylation, which is
      an inhibitory modification, ensued. In rat IEC-6 cell line, a significant higher
      level of AKT phosphorylation was observed at 2 h after heat exposure. This
      coincided with a marked reduction of apoptosis. CONCLUSION: Together, these
      results suggest that heat stress caused damages to rat jejunum and induced
      apoptosis to a greater degree. HSPs and pro-survival factors were involved in
      response to heat stress. Among them, AKT played a key role in inhibiting heat
      induced apoptosis.

PMID- 24295141
TI  - Comparison of a math fact rehearsal and a mnemonic strategy approach for
      improving math fact fluency.
AB  - The current study used a randomized controlled trial to compare the effects of a
      practice-based intervention and a mnemonic strategy intervention on the retention
      and application of single-digit multiplication facts with 90 third- and fourth
      grade students with math difficulties. Changes in retention and application were
      assessed separately using one-way ANCOVAs in which students' pretest scores were
      included as the covariate. Students in the practice-based intervention group had
      higher retention scores (expressed as the total number of digits correct per
      minute) relative to the control group. No statistically significant between-group
      differences were observed for application scores. Practical and theoretical
      implications for interventions targeting basic multiplication facts are
      discussed. 

PMID- 24295142
TI  - Children's intervention strategies in situations of victimization by bullying:
      social cognitions of outsiders versus defenders.
AB  - This study examined the social cognitions of outsiders and defenders about
      intervening in situations of victimization by bullying. Do outsiders and
      defenders behave differently in victimization situations because of differences
      in competence beliefs, or because of a selectivity effect in intervening? These
      issues were examined in a sample of 102 outsiders and 107 defenders who were
      classified into these bullying roles through a peer-nomination procedure out of a
      total sample of 761 10- to 14-year-old Dutch children. These children were
      presented with imaginary victimization events. They answered questions about
      their cognitions and self-efficacy beliefs about intervening in victimization
      situations and about handling such situations. Outsiders, compared to defenders,
      claimed to intervene indirectly in victimization situations rather than directly.
      Defenders, compared to outsiders, claimed to intervene directly in victimization
      situations rather than indirectly. Both outsiders and defenders claimed to be
      more likely to intervene when a friend was being victimized than when a neutral
      classmate was being victimized. Outsiders and defenders did not differ in their
      self-efficacy for indirect intervention, but only defenders claimed a high self
      efficacy for direct intervention. Both outsiders and defenders claimed to benefit
      from direct help when they themselves are victimized, but only outsiders also
      reported to need indirect help. The results suggest that outsiders and defenders
      behave differently in victimization situations because of differences in
      competence beliefs rather than because of a selectivity effect. More generally,
      the results suggest that not only defenders but also outsiders have the intention
      to help children who are being bullied. However, outsiders' anti-bullying
      attempts are likely to be indirect and less firm than those of defenders. 

PMID- 24295143
TI  - Instructional and behavior management practices implemented by elementary general
      education teachers.
AB  - This investigation examined 317 general education kindergarten through fifth
      grade teachers' use of instructional and behavioral management strategies as
      measured by the Classroom Strategy Scale (CSS)-Observer Form, a multidimensional
      tool for assessing classroom practices. The CSS generates frequency of strategy
      use and discrepancy scores reflecting the difference between recommended and
      actual frequencies of strategy use. Hierarchical linear models (HLMs) suggested
      that teachers' grade-level assignment was related to their frequency of using
      instructional and behavioral management strategies: Lower grade teachers utilized
      more clear 1 to 2 step commands, praise statements, and behavioral corrective
      feedback strategies than upper grade teachers, whereas upper grade teachers
      utilized more academic monitoring and feedback strategies, content/concept
      summaries, student focused learning and engagement, and student thinking
      strategies than lower grade teachers. Except for the use of praise statements,
      teachers' usage of instructional and behavioral management strategies was not
      found to be related to years of teaching experience or to the interaction of
      years of teaching experience and grade-level assignment. HLMs suggested that
      teachers' grade level was related to their discrepancy scores of some
      instructional and behavioral management strategies: Upper grade teachers had
      higher discrepancy scores in academic performance feedback, behavioral feedback,
      and praise than lower grade teachers. Teachers' discrepancy scores of
      instructional and behavioral management strategies were not found to be related
      to years of teaching experience or to the interaction of years of teaching
      experience and grade-level assignment. Implications of results for school
      psychology practice are outlined. 

PMID- 24295144
TI  - Temperament in early childhood and peer interactions in third grade: the role of
      teacher-child relationships in early elementary grades.
AB  - Children's interactions with peers in early childhood have been consistently
      linked to their academic and social outcomes. Although both child and classroom
      characteristics have been implicated as contributors to children's success, there
      has been scant research linking child temperament, teacher-child relationship
      quality, and peer interactions in the same study. The purpose of this study is to
      examine children's early temperament, rated at preschool age, as a predictor of
      interactions with peers (i.e., aggression, relational aggression, victimization,
      and prosociality) in third grade while considering teacher-child relationship
      quality in kindergarten through second grades as a moderator and mediator of this
      association. The sample (N=1364) was drawn from the NICHD Study of Early Child
      Care and Youth Development. Results from structural equation models indicated
      that teacher-child conflict in early elementary grades mediated links between
      children's temperament and later peer interactions. Findings underscore the
      importance of considering children's temperament traits and teacher-child
      relationship quality when examining the mechanisms of the development of peer
      interactions. 

PMID- 24295145
TI  - The efficacy of conjoint behavioral consultation on parents and children in the
      home setting: results of a randomized controlled trial.
AB  - The present study is a large-scale randomized trial testing the effects of a
      family-school partnership model (i.e., Conjoint Behavioral Consultation, CBC) for
      promoting behavioral competence and decreasing problem behaviors of children
      identified by their teachers as disruptive. CBC is a structured approach to
      problem-solving that involves consultants, parents, and teachers. The effects of
      CBC on family variables that are commonly associated with important outcomes
      among school-aged children (i.e., family involvement and parent competence in
      problem solving), as well as child outcomes at home, were evaluated. Participants
      were 207 children with disruptive behaviors from 91 classrooms in 21 schools in
      kindergarten through grade 3 and their parents and teachers. Results indicated
      that there were significantly different increases in home-school communication
      and parent competence in problem solving for participants in the CBC relative to
      control group. Likewise, compared to children in the control group, children in
      the CBC group showed significantly greater decreases in arguing, defiance,
      noncompliance, and tantrums. The degree of family risk moderated parents'
      competence in problem solving and children's total problem behaviors, teasing,
      and tantrums. 

PMID- 24295146
TI  - Work happiness among teachers: a day reconstruction study on the role of self
      concordance.
AB  - Self-concordant work motivation arises from one's authentic choices, personal
      values, and interests. In the present study, we investigated whether self
      concordant motivation may fluctuate from one work-related task to the next. On
      the basis of self-determination theory, we hypothesized that momentary self
      concordance buffers the negative impact of momentary work demands on momentary
      happiness. We developed a modified version of the day reconstruction method to
      investigate self-concordance, work demands, and happiness during specific work
      related tasks on a within-person and within-day level. In total, 132 teachers
      completed a daily diary on three consecutive work days as well as a background
      questionnaire. The daily diary resulted in 792 reported work activities and
      activity-related work demands, self-concordance, and happiness scores. Multilevel
      analysis showed that-for most work activities-state self-concordant motivation
      buffered the negative association of work demands with happiness. These findings
      add to the literature on motivation and well-being by showing that the levels of
      self-concordance and happiness experienced by employees vary significantly on a
      within-day level and show a predictable pattern. We discuss theoretical and
      practical implications of the findings to increase employees' well-being. 

PMID- 24295147
TI  - Exploratory structural equation modeling, bifactor models, and standard
      confirmatory factor analysis models: application to the BASC-2 Behavioral and
      Emotional Screening System Teacher Form.
AB  - Several psychological assessment instruments are based on the assumption of a
      general construct that is composed of multiple interrelated domains. Standard
      confirmatory factor analysis is often not well suited for examining the factor
      structure of such scales. This study used data from 1885 elementary school
      students (mean age=8.77 years, SD=1.47 years) to examine the factor structure of
      the Behavioral Assessment System for Children, Second Edition (BASC-2) Behavioral
      and Emotional Screening System (BESS) Teacher Form that was designed to assess
      general risk for emotional/behavioral difficulty among children. The modeling
      sequence included the relatively new exploratory structural equation modeling
      (ESEM) approach and bifactor models in addition to more standard techniques.
      Findings revealed that the factor structure of the BASC-2 BESS Teacher Form is
      multidimensional. Both ESEM and bifactor models showed good fit to the data.
      Bifactor models were preferred on conceptual grounds. Findings illuminate the
      hypothesis-generating power of ESEM and suggest that it might not be optimal for
      instruments designed to assess a predominant general factor underlying the data.

PMID- 24295148
TI  - Evidence is not sufficient to recommend a more aggressive approach to familial
      nonmedullary thyroid cancer.

PMID- 24295149
TI  - HLA-DRB1 associations with rheumatoid arthritis-related pulmonary fibrosis.

PMID- 24295150
TI  - Training providers: beyond the basics of electronic health records.
AB  - BACKGROUND: Training is a critical part of health information technology
      implementations, but little emphasis is placed on post-implementation training to
      support day-to-day activities. The goal of this study was to evaluate the impact
      of post-implementation training on key electronic health record activities.
      METHODS: Based on feedback from providers and requests for technical support, we
      developed two classes designed to improve providers' effectiveness with the
      electronic health record. Training took place at Kaiser Permanente, Mid-Atlantic
      States. The classes focused on managing patient-level information using problem
      lists and medication lists, as well as efficient documentation and chart review.
      Both classes used the blended learning method, integrating concrete scenarios,
      hands-on exercises and take-home materials to reinforce class concepts. To
      evaluate training effectiveness, we used a case-control study with a 1:4 match on
      pre-training performance. We measured the usage rate of two key electronic health
      record functions (problem list and medication list management) for six months
      before and after training. Change scores were compared using the Wilcoxon sign
      rank test. RESULTS: 36 participants and 144 non-participants were included in the
      training evaluation. Training participants were more likely to manage both
      medication lists and problem lists after training. Class material is now being
      incorporated into an enterprise-wide multi-modal training program available to
      all providers at Kaiser Permanente in the Mid-Atlantic States. CONCLUSIONS:
      Ongoing information technology training is well-received by healthcare providers,
      who expressed a clear preference for additional training. Training improved use
      of two important electronic health record features that are included as part of
      the Meaningful Use criteria.

PMID- 24295152
TI  - Estimating the prevalence of socially sensitive behaviors: attributing guilty and
      innocent noncompliance with the single sample count method.
AB  - Prevalence estimation models, using randomized or fuzzy responses, provide
      protection against exposure to respondents beyond anonymity and represent a
      useful research tool in socially sensitive situations. However, both guilty and
      innocent noncompliance can have a profound impact on prevalence estimations
      derived from these models. In this article, we introduce the maximum-likelihood
      extension of the single sample count (SSC-MLE) estimation model to detect and
      attribute noncompliance through testing 5 competing hypotheses on possible ways
      of noncompliance. We demonstrate the ability of the SSC-MLE to estimate and
      attribute noncompliance with a single sample using the observed distribution of
      affirmative answers on recent recreational drug use from a sample of university
      students (N = 1,441). Based on the survey answers, the drug use prevalence was
      estimated at 17.62% (+/- 6.75%), which is in line with relevant drug use
      statistics. Only 2.51% (+/- 1.54%) were noncompliant, of which 0.55% (+/- 0.44%)
      was attributed to guilty noncompliance (i.e., have used drugs but did not admit)
      and 2.17% (+/- 1.44%) to innocent noncompliers with no drug use in the past 3
      months to hide. The SSC-MLE indirect estimation method represents an important
      tool for estimating the prevalence of a broad range of socially sensitive
      behaviors. Subsequent applications of the SSC-MLE to a range of transgressive
      behaviors with varying sensitivity will contribute to establishing the SSC-MLE's
      performance properties, along with obtaining empirical evidence to test the
      underlying assumption of independence of noncompliance from involvement. Freely
      downloadable, user-friendly software to facilitate applications of the SSC-MLE
      model is provided.

PMID- 24295151
TI  - The thioredoxin reductase-1 inhibitor aurothioglucose attenuates lung injury and
      improves survival in a murine model of acute respiratory distress syndrome.
AB  - AIMS: Inflammation and oxygen toxicity increase free radical production and
      contribute to the development of acute respiratory distress syndrome (ARDS),
      which is a significant cause of morbidity and mortality in intensive care
      patients. We have previously reported increased glutathione (GSH) levels in lung
      epithelial cells in vitro and attenuated adult murine hyperoxic lung injury in
      vivo after pharmacological thioredoxin reductase-1 (TrxR1) inhibition. Using a
      murine ARDS model, we tested the hypothesis that aurothioglucose (ATG) treatment
      increases pulmonary GSH levels, attenuates lung injury, and decreases mortality
      in a GSH-dependent manner. RESULTS: Adult mice received a single intratracheal
      dose of 0.375 MUg/g lipopolysaccharide (LPS) 12 h before a single intraperitoneal
      injection of 25 mg/kg ATG. Control mice received intratracheal and/or
      intraperitoneal saline. Mice were then exposed to room air or hyperoxia (>95%
      O2). Lung injury was assessed by bronchoalveolar lavage protein concentrations.
      Expression of glutamate-cysteine ligase modifier subunit (GCLM), GSH, cytokines,
      and chemokines was determined. Exposure to LPS/hyperoxia induced inflammation and
      lung injury. ATG treatment significantly attenuated lung injury, increased lung
      GCLM expression and GSH levels, and decreased mortality. GSH depletion completely
      prevented the protective effects of ATG in LPS/hyperoxia-exposed mice.
      INNOVATION: ATG treatment significantly attenuates lung injury and enhances
      survival in a clinically relevant murine model of ARDS. The protective effects of
      ATG are GSH dependent. CONCLUSION: Augmentation of GSH systems by TrxR1
      inhibition could represent a promising therapeutic approach to attenuate oxidant
      mediated lung injury and improve patient outcomes.

PMID- 24295153
TI  - Uptake and speciation of vanadium in the benthic invertebrate Hyalella azteca.
AB  - Vanadium has the potential to leach into the environment from petroleum coke, an
      oil sands byproduct. To determine uptake of vanadium species in the biota, we
      exposed the benthic invertebrate Hyalella azteca with increasing concentrations
      of two different vanadium species, V(IV) and V(V), for seven days. The
      concentrations of vanadium in the H. azteca tissue increased with the
      concentration of vanadium in the exposure water. Speciation analysis revealed
      that V(IV) in the exposure water was oxidized to V(V) between renewal periods,
      and therefore the animals were mostly exposed to V(V). Speciation analysis of the
      H. azteca tissue showed the presence of V(V), V(IV), and an unidentified vanadium
      species. These results indicate the uptake and metabolism of vanadium by H.
      azteca. Because H. azteca are widely distributed in freshwater systems and are an
      important food supply for many fish, determining the uptake and metabolism of
      vanadium allows for a better understanding of the potential environmental effects
      on invertebrates. 

PMID- 24295154
TI  - Expression levels of seven candidate genes in human peripheral blood mononuclear
      cells and their association with preeclampsia.
AB  - OBJECTIVE: To evaluate the peripheral blood mononuclear cell (PBMC) expression
      levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular
      endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF
      beta1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association
      with preeclampsia (PE). METHODS: A total of 177 pregnant women were recruited:
      108 cases and 69 controls. Quantification of gene expression was measured by
      quantitative real-time polymerase chain reaction (PCR) using TaqMan probes.
      RESULTS: Underexpression of VEGF-A and TGF-beta1 was a constant in most of the
      cases (80.91% and 76.36%, respectively) and their expression was associated with
      onset and/or severity of disease (p values < 0.05). IL-6, IL-15 and AdipoQ,
      showed low or no expression in PBMC samples evaluated. CONCLUSION: PBMC
      underexpression of VEGF-A and TGF-beta1 is a hallmark of PE in the study
      population.

PMID- 24295155
TI  - Homophobic stigma, depression, self-efficacy and unprotected anal intercourse for
      peri-urban township men who have sex with men in Cape Town, South Africa: a cross
      sectional association model.
AB  - While research now highlights that men who have sex with men (MSM) in places such
      as South Africa are at particular risk of HIV infection, left relatively
      unexplored are potential relationships between one of the most pressing social
      issues affecting peri-urban MSM - namely homophobic stigma - and sexual risk
      taking behaviour. Drawing on research from the Ukwazana baseline study of 316
      township MSM in Cape Town we examine how homophobic stigma relates to
      psychosocial factors such as depression and self-efficacy and the risk activity
      of unprotected anal intercourse (UAI). By deploying cross-sectional association
      models, we examine a series of relationships between these variables and offer
      evidence to suggest that HIV prevention programmes aimed at sexual minority
      groups should be mindful of potentially complex relationships between social
      stigmas such as homophobia and sexual risk-taking behaviour.

PMID- 24295156
TI  - Impact of hydration state and molecular oxygen on the chemical stability of
      levothyroxine sodium.
AB  - Levothyroxine sodium is an important medication used primarily for treating
      patients with hypothyroidism. Levothyroxine sodium tablets have been recalled
      many times since their 1955 introduction to the US market. These recalls resulted
      from the failure of lots to meet their content uniformity and potency
      specifications. The purpose of this study is to test the hypothesis that the
      chemical stability of levothyroxine sodium pentahydrate is compromised upon
      exposing the dehydrated substance to molecular oxygen. The impact of temperature,
      oxygen and humidity storage conditions on the stability of solid-state
      levothyroxine sodium was examined. After exposure to these storage conditions for
      selected periods of time, high performance liquid chromatography (HPLC) was used
      to quantify the formation of impurities. The results showed that levothyroxine
      sodium samples degraded significantly over a 32-day test period when subjected to
      dry conditions in the presence of molecular oxygen. However, dehydrated samples
      remained stable when oxygen was removed from the storage chamber. Furthermore,
      hydrated samples were stable in the presence of oxygen and in the absence of
      oxygen. These results reveal conditions that will degrade levothyroxine sodium
      pentahydrate and elucidate measures that can be taken to stabilize the drug
      substance. 

PMID- 24295157
TI  - Initial evaluation and management of a first seizure in children.
AB  - The pediatrician is often the first health professional notified of a child's
      first seizure. First seizures cause much anxiety for parents and practitioners.
      Parents are frightened as they witness a paroxysmal event that involves
      convulsions or altered mental status, and as a result, they seek answers,
      reassurance, and support. Every pediatrician faces the challenge of determining
      whether a child who had a paroxysmal event had a seizure. Therefore, it is
      important for the general pediatrician to have a good understanding of the
      diagnosis and management of a child's first seizure. This review will discuss the
      definition of seizures and epilepsy, the critical questions to answer during the
      initial evaluation of a child's first seizure, guidance for initial management,
      risk factors for seizure recurrence, and the value of electroencephalography in
      diagnosis and treatment.

PMID- 24295158
TI  - Febrile seizures.
AB  - Febrile seizures are the most common form of childhood seizures, affecting 2% to
      5% of children. They are considered benign and self-limiting; however, a febrile
      seizure is a terrifying event for most parents, and is one of the most common
      causes of trips to the emergency room. A febrile seizure is "an event in infancy
      or childhood, usually occurring between 3 months and 5 years of age, associated
      with fever but without evidence of intracranial infection or defined cause." This
      definition excludes seizures with fever in children who have had a prior afebrile
      seizure. In 2011, The American Academy of Pediatrics (AAP) published a clinical
      practice guideline defining a febrile seizure as "a seizure accompanied by fever
      (temperature >= 100.4 degrees F or 38 degrees C by any method), without central
      nervous system infection, that occurs in infants and children 6 through 60 months
      of age." Febrile seizures are further classified as simple or complex. This
      article reviews the evaluation, management, and prognosis of simple and complex
      seizures, including febrile status epilepticus.

PMID- 24295159
TI  - Children with autism spectrum disorder and epilepsy.
AB  - Autism spectrum disorder (ASD) is a biologically based neurodevelopmental
      disability characterized by qualitative and persistent deficits in social
      communication and social interaction and by the presence of restricted,
      repetitive, and stereotyped patterns of behavior. Symptoms must be present in
      early childhood and they must limit and impair everyday functioning. There is an
      increased prevalence of epilepsy and/or epileptiform electroencephalography (EEG)
      abnormalities in children with ASD. It is estimated that approximately one-third
      of children and adolescents with ASD experience seizures, but the relationship
      between epilepsy and autism is controversial. This article reviews the types of
      seizures associated with ASD, the EEG findings, and current treatment strategies.
      The article also describes syndromes associated with the autism phenotype and
      epilepsy.

PMID- 24295160
TI  - Rating the movies.

PMID- 24295162
TI  - Cyber bullying: what's a parent to do?

PMID- 24295163
TI  - A 12-year-old boy with increasing verbal aggression.

PMID- 24295164
TI  - Improving the diagnosis of acute otitis media: "seeing is believing".

PMID- 24295165
TI  - A 7-year-old Hispanic boy with acute onset of abdominal pain.

PMID- 24295166
TI  - Pediatric seizures.

PMID- 24295167
TI  - An overview of hemoglobinopathies and the interpretation of newborn screening
      results.

PMID- 24295168
TI  - Orbital decompression for thyroid-associated orbitopathy in England: trends over
      time and geographical variation.
AB  - AIMS: The aims of this study were to examine trends over time and geographical
      variation in the annual incidence of surgical orbital decompression for thyroid
      associated ophthalmopathy (TAO) in England. METHODS: Data on hospital admissions
      for orbital decompression surgery in patients with thyroid disease were analysed
      using English national Hospital Episode Statistics for admissions from 1991-2011.
      RESULTS: Annual rates of orbital decompression surgery performed for patients
      with thyroid disease increased from 0.06 (95% confidence interval, 0.04--0.09)
      per 100,000 population in 1991, to 0.62 (0.54--0.67) in 2008, and then fell to
      0.56 (0.48--0.60) in 2011. The surgical rate was highest in women aged 45--64
      years. Geographical analysis showed significant variation across strategic health
      authority areas in surgical rates, from 0.22 (0.14-0.35) to 1.04 (0.79-1.34)
      people per 100,000 population per year in 2007-2011. CONCLUSION: The incidence of
      orbital decompression surgery performed annually in England has increased
      substantially over the past two decades, but peaked in 2008 and decreased since
      then. Significant geographical variation exists in surgical rates. Potential
      reasons for the decline include improved management of thyroid disease itself,
      but altered threshold in medical versus surgical management of TAO may also have
      played a role. The Amsterdam Declaration and EUGOGO treatment guidelines may also
      have influenced decisions about whether to operate on these patients.

PMID- 24295169
TI  - (+)- and (-)-Cajanusine, a pair of new enantiomeric stilbene dimers with a new
      skeleton from the leaves of Cajanus cajan.
AB  - A pair of new enantiomeric stilbene dimers, (+)- and (-)-cajanusine [(+)-1 and (
      )-1], with a unique coupling pattern were isolated from the leaves of Cajanus
      cajan . Their structures including absolute configurations were elucidated on the
      basis of comprehensive spectroscopic and single-crystal X-ray diffraction
      analyses, as well as CD calculations. The plausible biogenetic pathway of 1 was
      also proposed. Additionally, (+/-)-1, (+)-1, and (-)-1 exhibited inhibitory
      activities on the growth of human hepatocellular carcinoma cells. 

PMID- 24295170
TI  - Overview of metabolism and bioavailability enhancement of polyphenols.
AB  - A proper diet is one of major factors contributing to good health and is directly
      related to general condition of the organism. Phenolic compounds are abundant in
      foods and beverages (fresh and processed fruits and vegetables, leguminous
      plants, cereals, herbs, spices, tea, coffee, wine, beer) and their pleiotropic
      biological activities result in numerous health beneficial effects. On the other
      hand, high reactivity and very large diversity in terms of structure and
      molecular weight renders polyphenols one of the most difficult groups of
      compounds to investigate, as evidenced by ambiguous and sometimes contradictory
      results of many studies. Furthermore, phenolics undergo metabolic
      transformations, which significantly change their biological activities. Here, we
      discuss some aspects of metabolism and absorption of phenolic compounds. On the
      basis of information reported in the literature as well as in summaries of
      clinical trials and patent applications, we also give an overview of strategies
      for enhancing their bioavailability. 

PMID- 24295172
TI  - Brightness enhanced DNA FIT-probes for wash-free RNA imaging in tissue.
AB  - Fluorogenic oligonucleotides enable RNA imaging in cells and tissues. A high
      responsiveness of fluorescence is required when unbound probes cannot be washed
      away. Furthermore, emission should be bright in order to enable detection against
      autofluorescent background. The development of fluorescence-quenched
      hybridization probes has led to remarkable improvement of fluorescence
      responsiveness. Yet, comparably little attention has been paid to the brightness
      of smart probes. We describe hybridization probes that combine responsiveness
      with a high brightness of the measured signal. The method relies upon quencher
      free DNA forced intercalation (FIT)-probes, in which two (or more) intercalator
      dyes of the thiazole orange (TO) family serve as nucleobase surrogates. Initial
      experiments on multi-TO-labeled probes led to improvements of responsiveness, but
      self-quenching limited their brightness. To enhance both brightness and
      responsiveness the highly responsive TO nucleoside was combined with the highly
      emissive oxazolopyridine analogue JO. Single-stranded TO/JO FIT-probes are dark.
      In the probe-target duplex, quenching caused by torsional twisting and dye-dye
      contact is prevented. The TO nucleoside appears to serve as a light collector
      that increases the extinction coefficient and transfers excitation energy to the
      JO emitter. This leads to very bright JO emission upon hybridization (F/F0 = 23,
      brightness = 43 mL mol(-1) cm(-1) at lambdaex = 516 nm). TO/JO FIT-probes allowed
      the direct fluorescence microscopic imaging of oskar mRNA within a complex
      tissue. Of note, RNA imaging was feasible under wide-field excitation conditions.
      The described protocol enables rapid RNA imaging in tissue without the need for
      cutting-edge equipment, time-consuming washing, or signal amplification. 

PMID- 24295171
TI  - Scent of a break-up: phylogeography and reproductive trait divergences in the red
      tailed bumblebee (Bombus lapidarius).
AB  - BACKGROUND: The Pleistocene climatic oscillations are considered as a major
      driving force of intraspecific divergence and speciation. During Ice Ages,
      populations isolated in allopatric glacial refugia can experience differentiation
      in reproductive traits through divergence in selection regimes. This phenomenon
      may lead to reproductive isolation and dramatically accentuates the consequences
      of the climatic oscillations on species. Alternatively, when reproductive
      isolation is incomplete and populations are expanding again, further mating
      between the formerly isolated populations can result in the formation of a hybrid
      zone, genetic introgression or reinforcement speciation through reproductive
      trait displacements. Therefore changes in reproductive traits driven by
      population movements during climatic oscillations can act as an important force
      in promoting pre-zygotic isolation. Notwithstanding, divergence of reproductive
      traits has not been approached in the context of climatic oscillations. Here we
      investigate the impact of population movements driven by climatic oscillations on
      a reproductive trait of a bumblebee species (Bombus lapidarius). We characterise
      the pattern of variation and differentiation across the species distribution (i)
      with five genes (nuclear and mitochondrial), and (ii) in the chemical composition
      of male marking secretions (MMS), a key trait for mate attraction in bumblebees.
      RESULTS: Our results provide evidence that populations have experienced a genetic
      allopatric differentiation, in at least three main refugia (the Balkans, Centre
      Eastern Europe, and Southern Italy) during Quaternary glaciations. The
      comparative chemical analyses show that populations from the Southern Italian
      refugium have experienced MMS differentiation and an incipient speciation process
      from another refugium. The meeting of Southern Italian populations with other
      populations as a result of range expansion at a secondary contact zone seems to
      have led to a reinforcement process on local MMS patterns. CONCLUSIONS: This
      study suggests that population movement during Quaternary climatic oscillations
      can lead to divergence in reproductive traits by allopatric differentiation
      during Ice Ages and by reinforcement during post-glacial recolonization.

PMID- 24295173
TI  - Treatment outcome of docetaxel, capecitabine and cisplatin regimen for patients
      with refractory and relapsed nasopharyngeal carcinoma who failed previous
      platinum-based chemotherapy.
AB  - OBJECTIVE: Although cisplatin combined with 5-fluorouracil is a common first-line
      regimen for advanced nasopharyngeal carcinoma (NPC), there are no standard
      regimens for refractory or relapsed patients. A study of DXD regimen [cisplatin
      (D), capecitabine (X) and docetaxel (D)] was conducted to evaluate the efficacy
      and toxicity for patients with refractory or relapsed NPC. METHODS: The regimen
      was administered as follows: 50 mg/m(2) docetaxel and 50 mg/m(2) cisplatin on day
      1 and 800 mg/m2 capecitabine on days 1 - 14, repeated every 3 - 4 weeks. RESULTS:
      Thirty patients were enrolled. The overall response and complete remission rate
      was 46.4 and 21.4%. Median follow-up was 24 months; median overall survival (OS)
      and progression-free survival (PFS) were 14.0 and 8.0 months. Five-year OS and
      PFS rates were 14.8 and 13.3%, respectively. Four patients achieved long-term
      tumor-free survival (range, 53.8 - 125.3 months). Multivariate analysis
      demonstrated that Epstein-Barr virus DNA status (p = 0.003) and therapeutic
      effect (p < 0.001) were significant independent factors for OS and PFS. The main
      grade 3/4 toxicities included neutropenia (26.6%), anemia (13.3%) and
      thrombocytopenia (10.0%). There were no chemotherapy-related deaths. CONCLUSION:
      The DXD regimen appeared to be effective and well tolerated by patients with
      refractory or relapsed NPC. Further investigation is warranted.

PMID- 24295174
TI  - Statins and cancer.
AB  - Statins have pleiotropic properties and might exert an effect even in the field
      of cancer. Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme (HMG
      CoA) reductase, the major rate-limiting enzyme that controls the conversion of
      HMG-CoA to mevalonic acid. Specifically, inhibition of HMG-CoA reductase by
      statins has been proved to prevent the synthesis of mevalonic acid, a precursor
      of non-steroidal isoprenoids, which are lipid attachment molecules for small G
      proteins, such as Ras, Rho and Rac. Thus, statins may inhibit the synthesis of
      isoprenoids and thereby suppress the activation of small G proteins. In addition,
      statins exert pro-apoptotic, anti-angiogenic, and immunomodulatory effects, which
      may prevent cancer growth. Statins may inhibit the growth of a variety of cancer
      cell types, including breast, gastric, pancreatic, and prostate carcinoma,
      neuroblastoma, melanoma, mesothelioma and acute myeloid leukemia cells. They
      exert pro-apoptotic effects in a wide range of cancer cell lines, but with many
      differences in the sensitivity to statin-induced cell death among different
      cancer cell types. Regarding anti-angiogenic effects, multiple statin effects on
      blood vessel formation by inhibition of angiogenesis through down-regulation of
      pro-angiogenic factors, such as vascular endothelial growth factor, inhibition of
      endothelial cell proliferation and inhibition of adhesion to extracellular matrix
      by blocking intercellular adhesion molecules have been suggested. The molecular
      mechanisms of statin immunomodulation often implicate multiple pathways,
      regarding the regulation of genes encoding key molecules, which are involved in
      antigen presentation and subsequent immunomodulation. Another mechanism involves
      the down-regulation of the nuclear factor-kappa-B, which is responsible for the
      transcription of many genes involved in immunologic mechanisms, such as
      interferon-inducible protein-10, monocyte chemo-attractant protein 1 and
      cyclooxygenase-2. Statins have been associated with a significantly lower risk of
      breast, colorectal, ovarian, pancreatic, lung cancers and lymphoma in several
      observational studies. On the other hand, other studies, including meta-analyses
      have raised concerns about the safety of statins among elderly patients. A recent
      study upon the relationship between statin use (prior to cancer diagnosis) and
      cancer-related mortality in the entire Danish population from 1995-2009 in adults
      > 40 years of age has been conducted. As compared to statin non-users, patients
      using statins prior to cancer diagnosis were 15% less likely to die from any
      cause or cancer specifically. Further investigation is needed to elaborate on
      their mode of action as well as their true significance on cancer prevention and
      perhaps as an adjuvant to cancer chemotherapy. 

PMID- 24295175
TI  - Efficiency of a rapid test for detection of tetrodotoxin in puffer fish.
AB  - The selling and importing of puffer fish species and their products was banned in
      Thailand in 2002, because of possible neurotoxic effects. However, the sale of
      their flesh is still happening in Thai markets. Standard methods for toxin
      quantification (HPLC and LC-MS) have significant limitations, therefore a lateral
      flow, immuno-chromatographic test (TTX-IC) was developed as a tool for rapid
      detection of toxin. A total of 750 puffer fishes (387 Lagocephalus lunaris(LL),
      and 363 Lagocephalus spadiceus (LS)) and 100 edible fishes were caught in
      Thailand from June 2011-February 2012. Screening of TTX from their flesh by TTX
      IC revealed that 69 samples (17.8%) of LL possessed TTX at dangerous levels but
      LS and edible fishes did not. A selected 339 samples were quantified by LC-MS/MS,
      showing 50 LL possessed TTX at dangerous levels. Comparison of results with LC
      MS/MS showed the TTX-IC to have 94.0% sensitivity and 92.4% specificity. The TTX
      IC will be a useful tool for TTX screening of a large number of samples, reducing
      the testing required by LC-MS/MS, thus reducing costs. All positive cases found
      should be confirmed by standard methods. 

PMID- 24295176
TI  - Evaluation of diagnostic potential of Rv3803c and Rv2626c recombinant antigens in
      TB endemic country Pakistan.
AB  - To overcome and eliminate tuberculosis (TB), definitive, reliable, and rapid
      diagnosis is mandatory. Presently, the diagnostic potential of acute and latent
      stage TB specific antigens i.e., Rv3803c and Rv2626c was determined. Immunogenic
      recombinant genes of Rv3803c and Rv2626c antigens were cloned in bacterial
      expression vector pET23b and expressed product was purified. The homogeneity and
      structural integrity was confirmed by Western blot analysis. Diagnostic potential
      of Rv3803c and Rv2626c antigens was analyzed using the sera of 140 active TB
      patients (AFB smear positive) by indirect ELISA. Ten patients of leprosy and 94
      healthy individuals were taken as disease and normal control respectively. The
      data was analyzed using R statistical package. The sensitivity and specificity of
      Rv3803c in active TB patients was of 69.3% and 76.4% respectively with an area
      under ROC curve of 0.77, whereas sensitivity and specificity of Rv2626c 77.1% and
      85.1%, respectively. The area under ROC curve of Rv2626c was 0.89 which was
      significantly higher than Rv3803c (p < 0.0001). Recombinant antigens Rv3803c and
      Rv2626c have potential to be used as diagnostic markers for TB and need to
      evaluate with other antigens for differential diagnosis of TB.

PMID- 24295177
TI  - A highly sensitive polyclonal antibody-based ELISA for therapeutic monitoring and
      pharmacokinetic studies of lenalidomide.
AB  - This article describes, for the first time, a highly sensitive and specific
      enzyme-linked immunosorbent assay (ELISA) for therapeutic monitoring and
      pharmacokinetic studies of lenalidomide (LND), the potent drug for treatment of
      multiple myeloma (MM). The assay employed a polyclonal antibody that specifically
      recognizes LND with high affinity, and LND conjugate of bovine serum albumin (LND
      BSA) immobilized onto microplate wells as a solid phase. The assay involved a
      competitive binding reaction between LND, in plasma sample, and the immobilized
      LND-BSA for the binding sites on a limited amount of the anti-LND antibody. The
      assay limit of detection was 0.05 ng/mL and the effective working range at
      relative standard deviations (RSD) of <=5% was 0.1-20 ng/mL. Analytical recovery
      of LND from spiked plasma was 100.98 +/- 3.05. The precisions of the assay were
      satisfactory; RSD was 2.96-6.67% and 4.46-7.14%, for the intra- and inter-assay
      precision, respectively. The procedure is convenient, and one can analyze ~200
      samples per working day, facilitating the processing of large-number batch of
      samples in clinical laboratories. The proposed ELISA has a great value in routine
      analysis of LND for its therapeutic monitoring and pharmacokinetic studies.

PMID- 24295178
TI  - Influence of iodothyronine conjugates of bovine serum albumin and horseradish
      peroxidase on enzyme immunosorbent assay of thyroid hormones.
AB  - Enzyme-linked immunosorbent assays (ELISA's) reported for thyroxine (T4) and
      3,5,3'-triiodothyronine (T3), involved coupling of the haptens through (i)
      carboxylic group to carrier protein for producing antibodies and (ii) amino group
      to detection labels. To improve the titer and specificity of antibodies,
      immunogens were prepared by coupling of carboxyl group to bovine serum albumin
      (BSA) either directly or through adipic acid dihydrazide (ADH), after protecting
      amino group through acetylation of T4 and T3. Direct coupling resulted in the
      incorporation of 40-50 moles of T4 and T3 per BSA molecule and helped in
      improving immunogenic response and specificity, especially of T4. High epitope
      density of immunogens evoked better antibody response, since attachement of ADH
      as spacer, introduced 18-27 moles of haptens into carrier protein and had less
      effect on antibody development, with T3 being exception. Detection labels were
      prepared by coupling horseradish peroxidase (HRP) to amino group of thyroid
      hormones directly and after preparing their methyl esters, which provided
      sensitive displacement curves in combination with the antibodies developed
      against N-acetylated-T4 and T3. Unlike methyl esters, T4-HRP and T3-HRP showed
      higher sensitivity and seemed to be related to the affinity of the labels for
      binding the antibody.

PMID- 24295179
TI  - Effect of different combinations of antibodies and enzyme labels on ELISA of
      progesterone.
AB  - In steroid immunoassays, selection of right combination of antibody and enzyme
      labeled antigen determine the sensitivity and specificity of ELISA. Antibodies
      raised against different positions of progesterone adopting heterologous systems
      were reported to provide better assays for progesterone. Four different
      antibodies developed against progesterone-11alpha-hemiglutarate-BSA (P-11-HG
      BSA), progesterone-11alpha-hemisuccinate-BSA (P-11-HS-BSA), progesterone-3-O
      carboxymethyloxime-BSA (P-3-CMO-BSA), and progesterone-3-O-carboxymethyloxime
      ovalbumin (P-3-CMO-ova) were tested in combination with enzyme-labeled P-11-HG, P
      11-HS, progesterone-11alpha-carboxymethyl ether (P-11-CME), P-3-CMO, 17
      hydroxyprogesterone-3-O-carboxymethyl oxime (17-P-3-CMO), and progesterone-4
      carboxymethyl thioether (P-4-CMTE). These were variously labeled with
      penicillinase, alkaline phosphatase (ALP), and horseradish peroxidase (HRP). When
      antibody developed against P-11-HS-BSA was tested with P-3-CMO labeled separately
      with penicillinase, ALP, and HRP, the type of enzyme used had no effect on the
      performance of the assay. It was found that a homologous assay using P-3-CMO-ova
      as immunogen and P-3-CMO-HRP as label, as well as a heterologous ELISA with
      antibody raised against P-11-HS-BSA in combination with P-3-CMO-HRP, provided
      sensitive assays for progesterone. The use of 17alpha-hydroxy progesterone-3-O
      carboxymethyl oxime-HRP with the same antibodies against P-3-CMO-BSA and P-11-HS
      BSA also proved to be better than P-3-CMO-HRP. These findings implied that the
      sensitivity and specificity of ELISA to a great extent depended on the nature of
      the antibody produced, while the choice of enzyme labels could be manipulated.

PMID- 24295180
TI  - Characterization of a tuberculosis patient's sera reactive Mycobacterium
      tuberculosis transcription factor Rv2175c.
AB  - The transcriptional factor plays an important role in the regulation of gene
      expression and crucial to understand the biology of organisms. Mycobacterium
      tuberculosis, the causative agent of tuberculosis, harbors multiple
      transcriptional factors. Few transcriptional factors are well-documented
      antigens. Based on the screening of antigen with TB patients sera, a functional
      unknown ORF (Rv2175c) annotated as transcriptional factor was heterologously
      expressed, purified and for serodiagnostic value. E.coli recombinant Rv2175c
      protein was produced and antibodies were generated in rabbit using the
      recombinant antigens. ELISA and novel electrochemical immunosensor were employed
      in a parallel fashion in order to define its serodiagnositic value.
      Electrochemical immunosensor showed a sharp difference between health and TB
      sera. The data showed that Rv2715c is antigenic and can be used for TB
      seradignosis candidate in non BCG vaccinated areas. 

PMID- 24295181
TI  - Detection of host-specific immunogenic proteins in the saliva of patients with
      oral squamous cell carcinoma.
AB  - The main purpose of this article is to develop a new and reliable saliva-based
      clinical diagnostic method for the early detection of oral squamous cell
      carcinoma (OSCC). This study used an immunoproteomic approach which allowed the
      detection of immunogenic host proteins in patients' samples using pooled human
      antibodies. In an attempt to investigate potential biomarkers of OSCC, two
      dimensional electrophoresis (2-DE) followed by immunoblotting of saliva from
      patients and controls were compared. The protein spots of interest were analyzed
      using 2-DE image analyzer and subsequently subjected to MALDI-TOF/TOF and then
      matched against NCBI database. The result showed that four protein clusters,
      namely Human Pancreatic Alpha-amylase (HPA), Human Salivary Amylase (sAA),
      keratin-10 (K-10), and Ga Module Complexed with Human Serum Albumin (GA-HSA), had
      exhibited immunoreactivity in western blot. The results are suggestive of the
      potential use of the differentially expressed saliva protein as tumor biomarkers
      for the detection of OSCC. However, further studies are recommended to validate
      this finding. 

PMID- 24295182
TI  - A simple and highly sensitive ELISA for screening of the alpha-thalassemia-1
      Southeast Asian-type deletion.
AB  - Couples in which both partners carry the alpha-thalassemia-1 trait have a 25%
      risk of hemoglobin Bart's hydrops fetalis in each pregnancy. Identification of
      alpha-thalassemia-1 trait is, therefore, necessary in order to control this
      severe form of alpha-thalassemia. We have generated monoclonal antibodies
      specific to the zeta-globin chain without cross reaction with other globin
      chains. A simple and sensitive ELISA was developed by using poly-l-lysine to
      increase the protein binding to the ELISA plate. The developed poly-l-lysine pre
      coated ELISA has a very high sensitivity (100%) and specificity (97%) for
      detection of carriers of alpha-thalassemia-1 with Southeast Asian-type deletion. 

PMID- 24295183
TI  - Skewness of TCR Vbeta of peripheral blood and synovial fluid of patients with
      rheumatoid arthritis.
AB  - To date, the complete mechanism of rheumatoid arthritis (RA) remain unclear, T
      cells have been proposed to play an important role in the disease initiation and
      progression. Presently, some researchers have reported that there were skewed TCR
      Vbeta in different samples of experimental animals or RA patients, such as in the
      peripheral blood, joints or synovial fluid, however, most of the results were not
      coincident or even conflict with each other. In this article, with real-time
      fluorescence quantitative PCR with DNA melting curving technique, we detected the
      bias of TCR Vbeta of RA patients, and found that although most of TCR Vbeta usage
      were different between peripheral blood and synovial fluid, the overview of all
      the Vbeta skewness was similar between the two samples. 

PMID- 24295185
TI  - Nursing genomics: practice implications every nurse should know.
AB  - Twenty-first century nurse clinicians, scientists, and educators must be informed
      of and become proficient in genetic competencies to provide the best available
      evidenced-based patient care. This article presents a historical context and
      basic applications of genetics, along with the attendant legal and ethical
      issues, to provide a framework for understanding genetics and the genomics
      applications used in clinical nursing practice. The implications of genomics are
      relevant to all areas of nursing practice, including risk assessment, education,
      clinical management, and future research. 

PMID- 24295186
TI  - Nursing genomics: its role in health trajectory.
AB  - The human genome, which is the complete set of human genetic information,
      significantly contributes to the health of an individual; it can lead to single
      or complex medical conditions (including cancer and heart disease) also affected
      by environmental and behavioral risk factors. To date, the challenges related to
      human genomics and nursing science focus on the following areas: (1) curriculum
      application, (2) advanced clinical practice in specific fields, and (3) hands-on
      bioscience laboratory skills. This review article summarizes current efforts and
      addresses critical components in nursing genomics. 

PMID- 24295187
TI  - How advances in genomics are changing patient care.
AB  - The completion of the Human Genome Project has led to a greater understanding of
      the role of genetics/genomics in the development of all common diseases, which is
      leading to the routine integration of genetics and genomics into all aspects of
      health care. This change in practice presents new challenges for health care
      professionals. This article provides an overview of how genetics/genomics has the
      potential to improve health care within many different clinical scenarios, and
      highlights the key issues for nurses working in a variety of settings. 

PMID- 24295188
TI  - Hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, cardiovascular
      disorder that carries the risk of sudden cardiac death. The prevalence of HCM is
      1:500 persons. The purpose of this article is to provide an overview of the
      pathophysiology, symptoms, complications, diagnostic testing, and treatment. The
      silent presentation of HCM presents unique diagnostic challenges and complicates
      prompt identification. Diagnostic testing and management strategies for the care
      of a person with HCM are discussed. HCM has individualized presentation and
      therefore requires individualized therapy. 

PMID- 24295189
TI  - The impact of genomics on oncology nursing.
AB  - Since 2003, genetics and genomics information has led to exciting new
      diagnostics, prognostics, and treatment options in oncology practice. Profiling
      of cancers offers providers insight into treatment and prognostic factors.
      Germline testing provides an individual with information for surveillance or
      therapy that may help them prevent cancer in their lifetime and options for
      family members as yet untouched by malignancy. This offers a challenge for
      oncology nurses and other oncology health care providers to become comfortable
      with incorporating education about genetics/genomics into their clinical practice
      and patient education. 

PMID- 24295190
TI  - Genetics' influence on patient experiences with a rare chronic disorder: a
      photovoice study of living with alpha-1 antitrypsin deficiency.
AB  - Patients with rare chronic disorders and their caregivers increasingly form
      communities to support and exchange social experiences. Because up to 10% of the
      United States population is affected by one of 5000 to 6000 rare disorders,
      efforts to understand the individuals and affected communities are important.
      This study was conducted using community-based participatory research approaches
      within a community of patients and caregivers living with alpha-1 antitrypsin
      (AAT) deficiency. Patient populations at some risk for lung transplant include
      individuals who smoked cigarettes and patients who underwent liver transplant in
      infancy and later adulthood due to accumulation of misfolded AAT within
      hepatocytes. 

PMID- 24295191
TI  - Nursing and genetic biobanks.
AB  - Biobanks function as vital components in genetic research, which often requires
      large disease-based or population-based biospecimens and clinical data to study
      complex or rare diseases. Genetic biobanks aim to provide resources for
      translational research focusing on rapidly moving scientific findings from the
      laboratory into health care practice. The nursing profession must evolve as
      genetic biobanking practices advance. Nursing involvement in genetic biobanking
      practices comes with a distinct set of educational, ethical, and practice
      competencies. In response to these growing competency standards, nursing science
      developed a conceptual framework and continues to study ethical considerations to
      guide genetic biobanking initiatives. 

PMID- 24295193
TI  - Integrating genetics and genomics into nursing curricula: you can do it too!
AB  - Rapid advances in knowledge and technology related to genomics cross health care
      disciplines and touch almost every aspect of patient care. The ability to
      sequence a genome holds the promise that health care can be personalized. Health
      care professionals are faced with a gap in the ability to use the rapidly
      expanding technology and knowledge related to genomics in practice. Yet, nurses
      are key to bridging the gap between genomic discoveries and the human experience
      of illness. This article presents a case study documenting the experience of five
      nursing schools/colleges of nursing as they work to integrate genetics and
      genomics into their curricula. 

PMID- 24295192
TI  - An overview of epigenetics in nursing.
AB  - Epigenetic changes to the genome are biochemical alterations to the DNA that do
      not change an individual's genome but do change and influence gene expression.
      The nursing profession is qualified to conduct and integrate epigenetic-focused
      nursing research into practice. This article discusses current epigenetic nursing
      research, provides an overview of how epigenetic research relates to nursing
      practice, makes recommendations, and provides epigenetic online resources for
      nursing research. An overview of major epigenetic studies in nursing (specific to
      childbirth studies, preeclampsia, metabolic syndrome, immunotherapy cancer, and
      pain) is provided, with recommendations on next steps. 

PMID- 24295194
TI  - Cytochrome p450, part 1: what nurses really need to know.
AB  - Although knowledge about the impact of cytochrome p450 on individual variations
      in drug response has been known for decades, the transition to clinical practice
      has not evolved. Nurses who administer and prescribe medications have a
      responsibility to their patients to understand the responses to medications that
      are mediated by this family of enzymes. An overview of the variations seen in
      drug responses based on genetics is presented with discussion focusing on the
      current prescriptive practices and limitations in clinical drug trials. 

PMID- 24295195
TI  - Cytochrome p450 part 2: what nurses need to know about the cytochrome p450 family
      systems.
AB  - To provide the best patient care related to medication administration and
      prescription, an understanding of the specific enzymes is essential. Enzymes
      affect the metabolizing of most medications that nurses administer and that nurse
      practitioners and physicians prescribe on a regular basis. More specifically, the
      most important p450 enzymes in drug metabolism are cytochrome p450 (CYP) 1A2, the
      CYP2C family, CYP2D6, and CYP3A4. In addition, the enzymes are instrumental in
      the body's reaction to environmental factors, some of which are carcinogens. 

PMID- 24295196
TI  - Cytochrome p450 part 3: drug interactions: essential concepts and considerations.
AB  - The most important considerations related to understanding cytochrome p450
      enzymes is the appreciation that all drug effects vary among individuals and,
      although there are multiple causes of these variations, drug effects are strongly
      influenced by genes. Nurses who administer and monitor, or prescribe, these
      medications can only be safe if there is understanding of these processes. The
      same enzyme may display a variety of functions and alterations, which can range
      from ultrarapid activity to no activity. Foods given with medications also can
      affect the metabolism of the medication. Each cytochrome p450 subfamily is
      instrumental in the metabolism of numerous drugs. 

PMID- 24295197
TI  - Genomics.

PMID- 24295198
TI  - Segmentation of abdomen MR images using kernel graph cuts with shape priors.
AB  - BACKGROUND: Abdominal organs segmentation of magnetic resonance (MR) images is an
      important but challenging task in medical image processing. Especially for
      abdominal tissues or organs, such as liver and kidney, MR imaging is a very
      difficult task due to the fact that MR images are affected by intensity
      inhomogeneity, weak boundary, noise and the presence of similar objects close to
      each other. METHOD: In this study, a novel method for tissue or organ
      segmentation in abdomen MR imaging is proposed; this method combines kernel graph
      cuts (KGC) with shape priors. First, the region growing algorithm and morphology
      operations are used to obtain the initial contour. Second, shape priors are
      obtained by training the shape templates, which were collected from different
      human subjects with kernel principle component analysis (KPCA) after the
      registration between all the shape templates and the initial contour. Finally, a
      new model is constructed by integrating the shape priors into the kernel graph
      cuts energy function. The entire process aims to obtain an accurate image
      segmentation. RESULTS: The proposed segmentation method has been applied to
      abdominal organs MR images. The results showed that a satisfying segmentation
      without boundary leakage and segmentation incorrect can be obtained also in
      presence of similar tissues. Quantitative experiments were conducted for
      comparing the proposed segmentation with other three methods: DRLSE, initial
      erosion contour and KGC without shape priors. The comparison is based on two
      quantitative performance measurements: the probabilistic rand index (PRI) and the
      variation of information (VoI). The proposed method has the highest PRI value
      (0.9912, 0.9983 and 0.9980 for liver, right kidney and left kidney respectively)
      and the lowest VoI values (1.6193, 0.3205 and 0.3217 for liver, right kidney and
      left kidney respectively). CONCLUSION: The proposed method can overcome boundary
      leakage. Moreover it can segment liver and kidneys in abdominal MR images without
      segmentation errors due to the presence of similar tissues. The shape priors
      based on KPCA was integrated into fully automatic graph cuts algorithm (KGC) to
      make the segmentation algorithm become more robust and accurate. Furthermore, if
      a shelter is placed onto the target boundary, the proposed method can still
      obtain satisfying segmentation results.

PMID- 24295199
TI  - Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic
      arthritis in a Taiwanese population.
AB  - OBJECTIVES: An elevated interleukin (IL)-1beta response in peripheral blood
      mononuclear cells (PBMCs) has been observed in systemic juvenile idiopathic
      arthritis (sJIA), suggesting a role for inflammasomes in the pathogenesis of JIA.
      We aimed to determine whether genetic polymorphisms of the NLRP3 inflammasome
      components confer risk for oligoarticular and polyarticular JIA in a Taiwanese
      population. METHOD: A total of 118 JIA patients and 103 healthy controls were
      genotyped for rs4353135 OR2B11/NLRP3 and rs2043211 CARD8 polymorphisms. Clinical
      laboratory data and serum IL-1beta of JIA patients were evaluated by medical
      chart review and enzyme-linked immunosorbent assay (ELISA), respectively. The
      production of IL-17 in lymphocytes of different genotype carriers was measured
      using flow cytometry. RESULTS: The variant rs4353135 G allele carrier conferred
      increased risk for oligoarticular and polyarticular JIA. The G allele was also
      found to be associated with higher levels of clinical inflammatory markers.
      Moreover, G variant carriers enhanced the lymphocyte IL-17 response. The G/G
      genotype further increased the need for treatment with the tumour necrosis factor
      (TNF) inhibitor etanercept. CONCLUSIONS: Our data indicate that the rs4353135
      OR2B11/NLRP3 polymorphism might be functional in, and could contribute to, the
      pathophysiology of oligoarticular and polyarticular JIA in a Taiwanese
      population.

PMID- 24295200
TI  - Total synthesis of (+)-cassaine utilizing an anionic polycyclization strategy.
AB  - A stereoselective total synthesis of (+)-cassaine (1) via an anionic
      polycyclization methodology is described. Commercially available (+)-carvone (5),
      the only chiral source, was used to fix the entire stereochemistry of the natural
      product. Anionic polycyclization of a new substituted 2-(methoxycarbonyl)cyclohex
      2-en-1-one (4) with known 1-phenylysulfinyl-3-penten-2-one (3) provided the
      versatile tricycle (2) with requisite stereochemistry. A sequence of functional
      group manipulations of tricycle (2) furnished the natural product 1. 

PMID- 24295201
TI  - Anti-TNF therapy and malignancy in spondyloarthritis in the Leuven
      spondyloarthritis biologics cohort (BIOSPAR).
AB  - OBJECTIVES: To report the incidence of malignancy in a large single-centre cohort
      in Belgium of patients with spondyloarthritis (SpA) treated with one or more anti
      TNF therapies and to compare the results with the incidence of malignancy in the
      Belgian population. METHODS: From September 2000 until March 2010, all SpA
      patients that started treatment with one or more anti-TNF therapies were included
      in this single-centre prospective longitudinal observational study. The primary
      outcome of this study was the incidence of malignancy after starting anti-TNF
      treatment. Incidence rates were compared with the incidence rates of malignancy
      in Belgium in 2008 for the 45-50 year-old population, as documented by the
      Belgian Cancer Registry. RESULTS: 231 patients with a mean age of 47.86 y were
      included for a total of 1020.74 patient years of treatment and 1199.83 patient
      years follow-up after the start of treatment. In our study population, 6 out of
      231 patients (2.6 %) developed a malignancy after the start of anti-TNF
      treatment. The overall incidence rate of malignancy in our study population is
      500.1 per 100000 patient years, indicating a higher incidence compared to the
      Belgian population. We see a higher incidence rate in females as well in males;
      standardised incidence ratios are in the same range for both (154.3 for females
      and 130.6 for males). CONCLUSIONS: We see a tendency towards a higher incidence
      of malignancy in SpA patients treated with anti-TNF therapy. However, it is not
      clear whether this increased risk is disease-related or treatment-related.

PMID- 24295202
TI  - Preparation and evaluation of an orally fast disintegrating tablet formulation
      containing a hydrophobic drug.
AB  - Orally fast disintegrating tablets (FDTs or ODTs) have received ever-increasing
      demand during the last decade, and the field has become a rapidly growing area in
      the pharmaceutical industry. Upon introduction into the mouth, these tablets
      dissolve or disintegrate in the mouth in the absence of additional water for easy
      administration of active pharmaceutical ingredients. Although the FDT area has
      passed its infancy, as shown by a large number of commercial products on the
      market, there are still many aspects to improve in the FDT formulations. Despite
      advances in the FDT technologies, formulation of hydrophobic drugs is still a
      challenge, especially when the amount of drug is high. In this study, a new
      solution is being developed to incorporate higher doses of a model hydrophobic
      drug; meloxicam, without affecting the fast disintegrating properties of the
      formulation. In order to enhance the solubilization of meloxicam in FDT
      formulations, beta cyclodextrin inclusion complex of the drug is prepared and
      FDTs containing meloxicam--beta cyclodextrin inclusion complex (F1 A and F2 A)
      were compared and evaluated with the FDTs containing pure meloxicam (F1 and F2)
      by means of in vitro quality control tests.

PMID- 24295203
TI  - Magnetic nanosensor for detection and profiling of erythrocyte-derived
      microvesicles.
AB  - During the course of their lifespan, erythrocytes actively shed phospholipid
      bound microvesicles (MVs). In stored blood, the number of these erythrocyte
      derived MVs has been observed to increase over time, suggesting their potential
      value as a quality metric for blood products. The lack of sensitive, standardized
      MV assays, however, poses a significant barrier to implementing MV analyses into
      clinical settings. Here, we report on a new nanotechnology platform capable of
      rapid and sensitive MV detection in packed red blood cell (pRBC) units. A filter
      assisted microfluidic device was designed to enrich MVs directly from pRBC units,
      and label them with target-specific magnetic nanoparticles. Subsequent detection
      using a miniaturized nuclear magnetic resonance system enabled accurate MV
      quantification as well as the detection of key molecular markers (CD44, CD47,
      CD55). When the developed platform was applied, MVs in stored blood units could
      also be monitored longitudinally. Our results showed that MV counts increase over
      time and, thus, could serve as an effective metric of blood aging. Furthermore,
      our studies found that MVs have the capacity to generate oxidative stress and
      consume nitric oxide. By advancing our understanding of MV biology, we expect
      that the developed platform will lead to improved blood product quality and
      transfusion safety. 

PMID- 24295204
TI  - Reduced herbicide leaching by in situ adsorption of herbicide-micelle
      formulations to soils.
AB  - Aiming to reduce herbicide leaching, "in situ" adsorption of herbicide-micelle
      formulations to soils was explored. Sulfentrazone or metolachlor were solubilized
      in cationic micelles, and these herbicide-micelle formulations were applied to
      sandy and alluvial soils. Sulfentrazone adsorption to the soils was negligible;
      however, its adsorption via its solubilization in micelles and their adsorption
      to the soil was significant and in good agreement with the Freundlich and
      Langmuir models. Adsorption of solubilized herbicide to the sandy soil was higher
      than to the alluvial soil. The low ratio between the surfactant concentration and
      the cation exchange capacity (CEC) of the alluvial soil brought upon micelle
      decomposition and reduction in herbicide adsorption. Therefore, an optimized
      ratio between surfactant and soil CEC was chosen to maximize herbicide retention.
      Even upon adding relatively low loadings of surfactant (0.075-0.3% w/w soil),
      herbicide leaching through the soils was significantly reduced (2-5-fold) in
      comparison with the commercial formulations. 

PMID- 24295205
TI  - Myogenesis in the sea urchin embryo: the molecular fingerprint of the myoblast
      precursors.
AB  - BACKGROUND: In sea urchin larvae the circumesophageal fibers form a prominent
      muscle system of mesodermal origin. Although the morphology and later development
      of this muscle system has been well-described, little is known about the
      molecular signature of these cells or their precise origin in the early embryo.
      As an invertebrate deuterostome that is more closely related to the vertebrates
      than other commonly used model systems in myogenesis, the sea urchin fills an
      important phylogenetic gap and provides a unique perspective on the evolution of
      muscle cell development. RESULTS: Here, we present a comprehensive description of
      the development of the sea urchin larval circumesophageal muscle lineage
      beginning with its mesodermal origin using high-resolution localization of the
      expression of several myogenic transcriptional regulators and differentiation
      genes. A few myoblasts are bilaterally distributed at the oral vegetal side of
      the tip of the archenteron and first appear at the late gastrula stage. The
      expression of the differentiation genes Myosin Heavy Chain, Tropomyosin I and II,
      as well as the regulatory genes MyoD2, FoxF, FoxC, FoxL1, Myocardin, Twist, and
      Tbx6 uniquely identify these cells. Interestingly, evolutionarily conserved
      myogenic factors such as Mef2, MyoR and Six1/2 are not expressed in sea urchin
      myoblasts but are found in other mesodermal domains of the tip of the
      archenteron. The regulatory states of these domains were characterized in detail.
      Moreover, using a combinatorial analysis of gene expression we followed the
      development of the FoxF/FoxC positive cells from the onset of expression to the
      end of gastrulation. Our data allowed us to build a complete map of the Non
      Skeletogenic Mesoderm at the very early gastrula stage, in which specific
      molecular signatures identify the precursors of different cell types. Among them,
      a small group of cells within the FoxY domain, which also express FoxC and SoxE,
      have been identified as plausible myoblast precursors. Together, these data
      support a very early gastrula stage segregation of the myogenic lineage.
      CONCLUSIONS: From this analysis, we are able to precisely define the regulatory
      and differentiation signatures of the circumesophageal muscle in the sea urchin
      embryo. Our findings have important implications in understanding the evolution
      of development of the muscle cell lineage at the molecular level. The data
      presented here suggest a high level of conservation of the myogenic specification
      mechanisms across wide phylogenetic distances, but also reveal clear cases of
      gene cooption.

PMID- 24295206
TI  - Lower ankle-brachial index is related to worse cognitive performance in old age.
AB  - OBJECTIVE: We aimed to study the associations between peripheral artery disease
      (PAD) and ankle-brachial index (ABI) and performance in a range of cognitive
      domains in nondemented elderly persons. METHODS: Data were collected within the
      Lothian Birth Cohort 1921 and 1936 studies. These are two narrow-age cohorts at
      age 87 (n = 170) and 73 (n = 748) years. ABI was analyzed as a dichotomous (PAD
      vs. no PAD) and a continuous measure. PAD was defined as having an ABI less than
      0.90. Measures of nonverbal reasoning, verbal declarative memory, verbal fluency,
      working memory, and processing speed were administered. Both samples were
      screened for dementia. RESULTS: We observed no significant differences in
      cognitive performance between persons with or without PAD. However, higher ABI
      was associated with better general cognition (beta = .23, p = .02, R2 change =
      .05) and processing speed (beta = .29, p < .01, R2 change = .08) in the older
      cohort and better processing speed (beta = .12, p < .01, R2 change = .01) in the
      younger cohort. This was after controlling for age, sex, and childhood mental
      ability and excluding persons with abnormally high ABI (>1.40) and a history of
      cardiovascular or cerebrovascular disease. CONCLUSION: Lower ABI is associated
      with worse cognitive performance in old age, especially in the oldest old (>85
      years), possibly because of long-term exposure to atherosclerotic disease.
      Interventions targeting PAD in persons free of manifest cardiovascular and
      cerebrovascular disease may reduce the incidence of cognitive impairment and
      dementia.

PMID- 24295208
TI  - Looking at radiation damage on prebiotic building blocks.
AB  - A number of complex organic molecules have been detected in the interstellar
      medium, as well as in meteorites or comets. Among them, some exobiologic-relevant
      molecules have attracted particular interest. In the hypothesis of an exogen
      transport of prebiotic building blocks at the origin of life, the survival of
      such species and particularly their resistance to the solar UV radiation or
      cosmic rays is a key issue. For that purpose, we have performed a theoretical
      approach of the charge transfer dynamics induced by collision of protons with
      nucleobases and the 2-deoxy-d-ribose sugar moiety in a wide collision energy
      range. Calculations have been carried out by means of ab initio quantum chemistry
      molecular methods and compared to previous theoretical results using carbon
      projectile ions. Qualitative trends can be exhibited on DNA or RNA building
      blocks damage, which may concern studies on prebiotic species under spatial
      radiation. 

PMID- 24295207
TI  - The next generation of orthotopic thyroid cancer models: immunocompetent
      orthotopic mouse models of BRAF V600E-positive papillary and anaplastic thyroid
      carcinoma.
AB  - BACKGROUND: While the development of new treatments for aggressive thyroid cancer
      has advanced in the last 10 years, progress has trailed headways made with other
      malignancies. A lack of reliable authenticated human cell lines and reproducible
      animal models is one major roadblock to preclinical testing of novel
      therapeutics. Existing xenograft and orthotopic mouse models of aggressive
      thyroid cancer rely on the implantation of highly passaged human thyroid
      carcinoma lines in immunodeficient mice. Genetically engineered models of
      papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are
      immunocompetent; however, slow and stochastic tumor development hinders high
      throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and
      synchronously in immunocompetent mice would facilitate the investigation of novel
      therapeutics and approaches. METHODS: We characterized and utilized mouse cell
      lines derived from PTC and ATC tumors arising in genetically engineered mice with
      thyroid-specific expression of endogenous Braf(V600E/WT) and deletion of either
      Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with
      luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands
      of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics
      were assessed. RESULTS: Large locally aggressive thyroid tumors form within one
      week of implantation. Tumors recapitulate their histologic subtype, including
      well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune
      cell infiltration. Tumor progression can be followed in vivo using luciferase and
      ex vivo using GFP. Metastatic spread is not detected at early time points.
      CONCLUSIONS: We describe the development of the next generation of murine
      orthotopic thyroid cancer models. The implantation of genetically defined murine
      BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and
      synchronous tumor formation. This model allows for preclinical investigation of
      novel therapeutics and/or therapeutic combinations in the context of a functional
      immune system.

PMID- 24295209
TI  - Spontaneous regression of a conjunctival malignant melanoma.
AB  - INTRODUCTION: Conjunctival malignant melanoma (MM) is a rare malignancy and
      accounts for 2% of all ocular malignancies. We describe what we believe to be the
      first reported case of complete spontaneous regression of a conjunctival
      malignant melanoma. METHODS: A 75-year-old female presented with a large,
      pigmented lesion in her left lower fornix. Histopathology revealed a mixed cell
      type MM. The tumour regressed spontaneously. Now, 6 years after she first
      presented, she remains well and there is no sign of recurrence or metastasis.
      CONCLUSION: Spontaneous regression is not always synonymous with complete cure
      from the underlying disease but may represent a temporary regression due to host
      protective mechanisms. In our patient regression and cure were complete.

PMID- 24295211
TI  - Spatial atmospheric atomic layer deposition of Al(x)Zn(1-x)O.
AB  - The possibility of growing multicomponent oxides by spatial atmospheric atomic
      layer deposition has been investigated. To this end, Al(x)Zn(1-x)O films have
      been deposited using diethyl zinc (DEZ), trimethyl aluminum (TMA), and water as
      Zn, Al, and O precursors, respectively. When the metal precursors (i.e., TMA and
      DEZ) are coinjected in the deposition region, the Al/(Al + Zn) ratio can be
      accurately controlled by either varying the TMA flow to the reactor or the
      exposure time of the substrate to the precursors. A high doping efficiency level
      (up to 70%) is achieved in Al-doped ZnO, resulting in films with a high carrier
      density (5 * 10(20) cm(-3)), low resistivity (2 * 10(-3) Omega cm), and good
      optical transparency (>85%) in the visible range. The morphology of the films
      changes from polycrystalline, in conductive i-ZnO and Al-doped ZnO, to amorphous,
      in highly resistive Al-rich films. The unique combination of the fine tuning of
      the composition, morphology, and electrical properties of the films with high
      deposition rates (>0.2 nm/s) paves the way for spatial ALD as an emerging
      disruptive technique for the growth of multicomponent oxides over large areas.

PMID- 24295210
TI  - Superhydrophobic photosensitizers. Mechanistic studies of (1)O2 generation in the
      plastron and solid/liquid droplet interface.
AB  - We describe here a physical-organic study of the first triphasic superhydrophobic
      sensitizer for photooxidations in water droplets. Control of synthetic parameters
      enables the mechanistic study of "borderline" two- and three-phase
      superhydrophobic sensitizer surfaces where (1)O2 is generated in compartments
      that are wetted, partially wetted, or remain dry in the plastron (i.e., air layer
      beneath the droplet). The superhydrophobic surface is synthesized by partially
      embedding silicon phthalocyanine (Pc) sensitizing particles to specific locations
      on polydimethylsiloxane (PDMS) posts printed in a square array (1 mm tall posts
      on 0.5 mm pitch). In the presence of red light and oxygen, singlet oxygen is
      formed on the superhydrophobic surface and reacts with 9,10-anthracene
      dipropionate dianion (1) within a freestanding water droplet to produce an
      endoperoxide in 54-72% yields. Control of the (1)O2 chemistry was achieved by the
      synthesis of superhydrophobic surfaces enriched with Pc particles either at the
      PDMS end-tips or at PDMS post bases. Much of the (1)O2 that reacts with
      anthracene 1 in the droplets was generated by the sensitizer "wetted" at the Pc
      particle/water droplet interface and gave the highest endoperoxide yields. About
      20% of the (1)O2 can be introduced into the droplet from the plastron. The
      results indicate that the superhydrophobic sensitizer surface offers a unique
      system to study (1)O2 transfer routes where a balance of gas and liquid
      contributions of (1)O2 is tunable within the same superhydrophobic surface. 

PMID- 24295212
TI  - Thermal sensitisation by lonidamine of human melanoma cells grown at low
      extracellular pH.
AB  - PURPOSE: This study tested the ability of lonidamine (LND), a clinically
      applicable inhibitor of monocarboxylate transporters (MCT), to thermally
      sensitise human melanoma cells cultured at a tumour-like extracellular pH (pHe)
      6.7. MATERIALS AND METHODS: Human melanoma DB-1 cells cultured at pHe 6.7 and pHe
      7.3 were exposed to 150 uM LND for 3 h, beginning 1 h prior to heating at 42 
      degrees C (2 h). Intracellular pH (pHi) was determined using 2',7'-bis-(2
      carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and whole spectrum analysis.
      Levels of heat shock proteins (HSPs) were determined by immunoblot analysis. Cell
      survival was determined by colony formation. RESULTS: Treatment with LND at pHe
      6.7 reduced pHi to 6.30 +/- 0.21, reduced thermal induction of HSPs, and
      sensitised cells growing at pHe 6.7 to 42  degrees C. When LND was combined with
      an acute acidification from pHe 6.7 to pHe 6.5, pHi was reduced to 6.09 +/- 0.26,
      and additional sensitisation was observed. LND had negligible effects on cells
      cultured at pH 7.3. CONCLUSIONS: The results show that LND can reduce pHi in
      human melanoma cells cultured at a tumour-like low pHe so that the 42  degrees C
      induction of HSPs are abrogated and the cells are sensitised to thermal therapy.
      Cells cultured at a normal tissue-like pHe 7.3 were not sensitised to 42  degrees
      C by LND. These findings support the strategy that human melanoma cells growing
      in an acidic environment can be sensitised to thermal therapy in vivo by exposure
      to an MCT inhibitor such as LND.

PMID- 24295213
TI  - Sonoporation as an enhancing method for boron neutron capture therapy for
      squamous cell carcinomas.
AB  - BACKGROUND: Boron neutron capture therapy (BNCT) is a selective radiotherapy that
      is dependent on the accumulation of 10B compound in tumors. Low-intensity
      ultrasound produces a transient pore on cell membranes, sonoporation, which
      enables extracellular materials to enter cells. The effect of sonoporation on
      BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice.
      MATERIALS AND METHODS: Tumor-bearing mice were administrated boronophenylalanine
      (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors
      were subjected to sonoporation using microbubbles followed by neutron
      irradiation. RESULTS: The 10B concentration was higher in tumors treated with
      sonoporation than in untreated tumors, although the difference was not
      significant in BPA. When tumors in mice that received BPA intraperitoneally were
      treated with sonoporation followed by exposure to thermal neutrons, tumor volume
      was markedly reduced and the survival rate was prolonged. Such enhancements by
      sonoporation were not observed in mice treated with BSH-mediated BNCT.
      CONCLUSIONS: These results indicate that sonoporation enhances the efficiency of
      BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization
      of BPA and BSH in tumors and increase their intracellular levels.

PMID- 24295215
TI  - Comment on: Think to prevent before than to treat renal impairment in multiple
      myeloma: do not forget tubular damage mimicking Fanconi syndrome.

PMID- 24295214
TI  - Genome-wide analysis of porcine backfat and intramuscular fat fatty acid
      composition using high-density genotyping and expression data.
AB  - BACKGROUND: Porcine fatty acid composition is a key factor for quality and
      nutritive value of pork. Several QTLs for fatty acid composition have been
      reported in diverse fat tissues. The results obtained so far seem to point out
      different genetic control of fatty acid composition conditional on the fat
      deposits. Those studies have been conducted using simple approaches and most of
      them focused on one single tissue. The first objective of the present study was
      to identify tissue-specific and tissue-consistent QTLs for fatty acid composition
      in backfat and intramuscular fat, combining linkage mapping and GWAS approaches
      and conducted under single and multitrait models. A second aim was to identify
      powerful candidate genes for these tissue-consistent QTLs, using microarray gene
      expression data and following a targeted genetical genomics approach. RESULTS:
      The single model analyses, linkage and GWAS, revealed over 30 and 20 chromosomal
      regions, 24 of them identified here for the first time, specifically associated
      to the content of diverse fatty acids in BF and IMF, respectively. The analyses
      with multitrait models allowed identifying for the first time with a formal
      statistical approach seven different regions with pleiotropic effects on
      particular fatty acids in both fat deposits. The most relevant were found on SSC8
      for C16:0 and C16:1(n-7) fatty acids, detected by both linkage and GWAS
      approaches. Other detected pleiotropic regions included one on SSC1 for C16:0,
      two on SSC4 for C16:0 and C18:2, one on SSC11 for C20:3 and the last one on SSC17
      for C16:0. Finally, a targeted eQTL scan focused on regions showing tissue
      consistent effects was conducted with Longissimus and fat gene expression data.
      Some powerful candidate genes and regions were identified such as the PBX1, RGS4,
      TRIB3 and a transcription regulatory element close to ELOVL6 gene to be further
      studied. CONCLUSIONS: Complementary genome scans have confirmed several
      chromosome regions previously associated to fatty acid composition in backfat and
      intramuscular fat, but even more, to identify new ones. Although most of the
      detected regions were tissue-specific, supporting the hypothesis that the major
      part of genes affecting fatty acid composition differs among tissues, seven
      chromosomal regions showed tissue-consistent effects. Additional gene expression
      analyses have revealed powerful target regions to carry the mutation responsible
      for the pleiotropic effects.

PMID- 24295216
TI  - Identification of disulfide bond formation between MitoNEET and glutamate
      dehydrogenase 1.
AB  - MitoNEET is a protein that was identified as a drug target for diabetes, but its
      cellular function as well as its role in diabetes remains elusive. Protein pull
      down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential
      binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin
      regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond
      formation and acts as an activator. Proteomic analysis identified the specific
      cysteine residues that participate in the disulfide bond. This is the first
      report that effectively links mitoNEET to activation of the insulin regulator
      GDH1. 

PMID- 24295218
TI  - Emergency skills learning on video (ESLOV): A single-blinded randomized control
      trial of teaching common emergency skills using self-instruction video (SIV)
      versus traditional face-to-face (FTF) methods.
AB  - BACKGROUND: Self-instruction video (SIV) has been widely explored as a teaching
      mode for cardiopulmonary resuscitation (CPR) and automated external
      defibrillation (AED), but not with other basic emergency skills. AIM: To evaluate
      the effectiveness of SIV in teaching other basic emergency skill in comparison
      with traditional face-to-face (FTF) methods. METHODS: Participants were
      randomized into SIV and FTF groups. Each group was assigned to learn basic airway
      management (BAM), cervical collar application (CCA), manual cardiac
      defibrillation (MCD), and emergency extremity splinting (EES) skills. Confidence
      level was assessed using questionnaires, and skills performances were assessed
      using calibrated-blinded assessors through an Objective Structured Clinical
      Examination (OSCE). RESULTS: Forty-five participants took part in the assessment
      exercises. There were no significant differences between both groups, on all four
      skill categories. The mean OSCE-score of an individual category between the FTF
      group vs. the SIV-group were as follows: BAM (10.23 +/- 1.04 vs. 10.04 +/- 1.49;
      p = 0.62); CCA (7.86 +/- 4.39 vs. 7.13 +/- 4.12; p = 0.57); MCD (8.24 +/- 0.89
      vs. 7.58 +/- 1.14; p = 0.39); EES (5.43 +/- 2.11 vs. 4.63 +/- 2.30; p = 0.23).
      The composite mean score for the FTF-group was 6.85, and for the SIV-group was
      6.20 (p < 0.05). There was no significant different in the level of confidence
      for both groups. CONCLUSION: SIV is as effective as FTF in teaching and learning
      basic emergency skills.

PMID- 24295217
TI  - alpha-Mangostin: a dietary antioxidant derived from the pericarp of Garcinia
      mangostana L. inhibits pancreatic tumor growth in xenograft mouse model.
AB  - AIMS: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as
      the fourth most leading cause of cancer-related death among men and women in the
      United States. In this study, we provide evidence of chemotherapeutic effects of
      alpha-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia
      mangostana L. against human PC. RESULTS: The chemotherapeutic effect of alpha
      mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and
      ASPC1). alpha-Mangostin resulted in a significant inhibition of PC cells
      viability without having any effects on normal human pancreatic duct epithelial
      cells. alpha-Mangostin showed a dose-dependent increase of apoptosis in PC cells.
      Also, alpha-mangostin inhibited the expression levels of pNF-kappaB/p65Ser552,
      pStat3Ser727, and pStat3Tyr705. alpha-Mangostin inhibited DNA binding activity of
      nuclear factor kappa B (NF-kappaB) and signal transducer and activator 3 (Stat3).
      alpha-Mangostin inhibited the expression levels of matrix metallopeptidase 9
      (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor
      of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p.
      administration of alpha-mangostin (6 mg/kg body weight, 5 days a week) resulted
      in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human
      PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No
      sign of toxicity was observed in any of the mice administered with alpha
      mangostin. alpha-Mangostin treatment inhibited the biomarkers of cell
      proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the
      xenograft tumor tissues. INNOVATION: We present, for the first time, that dietary
      antioxidant alpha-mangostin inhibits the growth of PC cells in vitro and in vivo.
      CONCLUSION: These results suggest the potential therapeutic efficacy of alpha
      mangostin against human PC.

PMID- 24295219
TI  - Does donor-recipient age difference matter in outcome of kidney transplantation?
      Implications for kidney paired donation.
AB  - BACKGROUND: Kidney paired donation (KPD) is a rapidly growing modality for
      facilitating living donor kidney transplantation (LDKTx) for patients who are
      incompatible with their healthy, willing and living donor. The impact of donor
      recipient age difference on long and short-term graft and patient survivals in
      LDKTx is still uncertain. METHODS: A total of 1502 LDKTx recipients who received
      regular follow-up in our center from 1999 to 2012 were studied. Donor-recipient
      age difference was divided into subgroups (donor-recipient 0-10, 11-20, 0-20, 21
      30, 31-40, and 21-40 years). Outcome measures included death censored graft,
      patient survival and acute rejection rate. RESULTS: The 1-, 5-, 10-year patient
      survival of the donor-recipient age difference <=20 years group showed no
      difference compared with the age difference >20 years group (94.5%, 83.2%, 71.9%
      and 95.2%, 86%, 77.8%, p = 0.053). The 1-, 5-, 10-year graft survival of the
      donor-recipient age difference <=20 years group showed no difference compared
      with the age difference >20 years group (94.6%, 81.6%, 72.1% and 94%, 80%, 72.2%,
      p = 0.989). The rejection were also similar (17.5% vs. 16.5%, p > 0.05). There
      was no statistically significant difference in graft survival and acute rejection
      rate in all subgroups. CONCLUSIONS: Older donors (usually within families) are
      not associated with worse outcome is reassuring. KPD should not be prohibited due
      to high donor-recipient age difference, when size of donor pool is small as in
      single center KPD program.

PMID- 24295220
TI  - N-Heterocyclic carbene catalyzed reaction of cinnamils leading to the formation
      of 2,3,8-triaryl vinyl fulvenes: an uncommon transformation.
AB  - An unexpected transformation of 1,6-diarylhexa-1,5-diene-3,4-diones (cinnamils)
      to 2,3,8-triaryl vinyl fulvenes via N-Heterocyclic Carbene (NHC) catalysis is
      reported. Mechanistic as well as synthetic novelty is the hallmark of this
      reaction. 

PMID- 24295222
TI  - New highly in vitro antioxidative 3,8"-linked Biflav(an)ones and Flavanone-C
      glycosides from Garcinia buchananii stem bark.
AB  - Very recently, we described highly antioxidative polyphenols isolated from the
      stem bark extract of the Garcinia buchananii tree. In this study, we describe
      additional antioxidants from Garcinia buchananii bark extract using hydrogen
      peroxide scavenging, oxygen radical absorbance capacity (ORAC), and trolox
      equivalent antioxidant capacity (TEAC) assays. UPLC-HR-ESI-TOF-MS(e) analysis, 1-
      and 2D-NMR, and circular dichroism (CD) spectroscopy led to the unequivocal
      identification of the antioxidative molecules as a series of five 3,8"-linked
      biflav(an)ones and two flavanone-C-glycosides. (2S,3R)-Taxifolin-6-C-beta-d
      glucopyranoside (2), (2R,3S,2"S,3"S)-manniflavanone (3), (2R,3S)
      buchananiflavonol (4), and (2S,3R,2"R,3"R)-GB-1 (6) are new compounds, and
      (2S,3S)-taxifolin-6-C-beta-d-glucopyranoside (1) was described so far only in one
      other plant. The structure of (2R,3S,2"R,3"R)-GB-1 (5) and (2R,3S,2"S)-GB2a (7)
      were confirmed. The H2O2 scavenging, TEAC, and the ORAC assays demonstrated that
      these natural products have an extraordinarily high antioxidative power,
      especially (2R,3S,2"S,3"S)-manniflavanone (3) with an EC50 value of 3.0 MUM, 4.00
      mmol TE/mmol, and 10.30 MUmol TE/ MUmol. 

PMID- 24295221
TI  - Maternal fish and shellfish consumption and wheeze, eczema and food allergy at
      age two: a prospective cohort study in Brittany, France.
AB  - BACKGROUND: Environmental exposures, including dietary contaminants, may
      influence the developing immune system. This study assesses the association
      between maternal pre-parturition consumption of seafood and wheeze, eczema, and
      food allergy in preschool children. Fish and shellfish were studied separately as
      they differ according to their levels of omega-3 polyunsaturated fatty acids
      (which have anti-allergic properties) and their levels of contaminants. METHODS:
      The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy.
      Maternal fish and shellfish intake was measured at inclusion by a food frequency
      questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire
      completed by the mother when the child was 2 years old (n = 1500). Examination of
      the associations between seafood intake and outcomes took major confounders into
      account. Complementary sensitivity analyses with multiple imputation enabled us
      to handle missing data, due mostly to attrition. RESULTS: Moderate maternal pre
      parturition fish intake (1 to 4 times a month) was, at borderline significance,
      associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before
      age 2, compared with low intake (< once/month). This result was not, however,
      consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17).
      Shellfish intake at least once a month was associated with a higher risk of food
      allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no
      intake (< once/month). Multiple imputation confirmed this association (adjusted
      OR = 1.52 (1.05-2.21)). CONCLUSIONS: This study suggests that maternal pre
      parturition shellfish consumption may increase the risk of food allergy. Further
      large-scale epidemiologic studies are needed to corroborate these results,
      identify the contaminants or components of shellfish responsible for the effects
      observed, determine the persistence of the associations seen at age 2, and
      investigate potential associations with health effects observable at later ages,
      such as allergic asthma.

PMID- 24295223
TI  - Self-assembled tetra- and pentanuclear nickel(II) aggregates from phenoxido-based
      ligand -bound {Ni2} fragments: carboxylate bridge controlled structures.
AB  - Three different carboxylato bridges (R = C2H5, CF3, and PhCH2 in RCO2(-)) have
      been used to obtain the supramolecular aggregates [Ni5(MU-H2bpmp)2(MU3-OH)2(MU1,3
      O2CC2H5)6].2H2O.4DMF (1.2H2O.4DMF), [Ni4(MU3-H2bpmp)2(MU3-OH)2(MU1,3
      O2CCF3)2](CF3CO2)2.H2O (2.H2O), and [Ni4(MU3-H2bpmp)2(MU3-OH)2(MU1,3
      O2CCH2Ph)2](PhCH2CO2)2.4H2O (3.4H2O) (H3bpmp =2,6-bis-[(3-hydroxy-propylimino)
      methyl]-4-methyl-phenol) from the hydroxido-bridged dinuclear motif [Ni2(MU
      H2bpmp)(OH)](2+). These complexes have been characterized by X-ray
      crystallography and magnetic measurements. A change from propanoate group to
      trifluoroacetate and phenylaceate groups provided different course of cluster
      assembly based on Ni2(MU-H2bpmp)2 fragments. The {Ni5(MU3-OH)2(MU1,3
      O2CC2H5)6}(2+) core in 1 contains five Ni(II) ions in an hourglass (pentanuclear
      vertex-shared double cubane) arrangement. These compounds are new examples of
      [Ni5] and [Ni4] complexes where aggregation of the building motifs are guided by
      the nature of the carboxylate anions, which allows an effective tuning of the
      self-aggregate process within same ligand environment. The study of the magnetic
      properties reveals that 1 exhibits an S = 3 ground state. Nevertheless, the
      magnetization increases above the expected saturation value of 6 MUB at higher
      fields, because of the suppression of antiferromagnetic exchange between the
      central and peripheral Ni(II) ions. Complexes 2 and 3 exhibit ferromagnetic
      exchange interactions that result in the S = 4 ground state. Examination of AC
      magnetic susceptibility showed that complex 2 in finely ground form behaves as
      spin glass with the spin-freezing temperature of ~5.5 K. This behavior was
      attributed to the collapse of the structure upon the loss of interstitial
      solvent. Such property was not observed for complex 3, in which the bulkier
      carboxylate ligands provide for a more robust crystal packing and larger
      separation between the [Ni4O4] clusters.

PMID- 24295224
TI  - Type-specific proactive interference in patients with semantic and phonological
      STM deficits.
AB  - Prior neuropsychological evidence suggests that semantic and phonological
      components of short-term memory (STM) are functionally and neurologically
      distinct. The current paper examines proactive interference (PI) from semantic
      and phonological information in two STM-impaired patients, DS (semantic STM
      deficit) and AK (phonological STM deficit). In Experiment 1 probe recognition
      tasks with open and closed sets of stimuli were used. Phonological PI was
      assessed using nonword items, and semantic and phonological PI was assessed using
      words. In Experiment 2 phonological and semantic PI was elicited by an item
      recognition probe test with stimuli that bore phonological and semantic relations
      to the probes. The data suggested heightened phonological PI for the semantic STM
      patient, and exaggerated effects of semantic PI in the phonological STM case. The
      findings are consistent with an account of extremely rapid decay of activated
      type-specific representations in cases of severely impaired phonological and
      semantic STM. 

PMID- 24295225
TI  - Formation of stacking faults and the screw dislocation-driven growth: a case
      study of aluminum nitride nanowires.
AB  - Stacking faults are an important class of crystal defects commonly observed in
      nanostructures of close packed crystal structures. They can bridge the transition
      between hexagonal wurtzite (WZ) and cubic zinc blende (ZB) phases, with the most
      known example represented by the "nanowire (NW) twinning superlattice".
      Understanding the formation mechanisms of stacking faults is crucial to better
      control them and thus enhance the capability of tailoring physical properties of
      nanomaterials through defect engineering. Here we provide a different perspective
      to the formation of stacking faults associated with the screw dislocation-driven
      growth mechanism of nanomaterials. With the use of NWs of WZ aluminum nitride
      (AlN) grown by a high-temperature nitridation method as the model system,
      dislocation-driven growth was first confirmed by transmission electron microscopy
      (TEM). Meanwhile numerous stacking faults and associated partial dislocations
      were also observed and identified to be the Type I stacking faults and the Frank
      partial dislocations, respectively, using high-resolution TEM. In contrast, AlN
      NWs obtained by rapid quenching after growth displayed no stacking faults or
      partial dislocations; instead many of them had voids that were associated with
      the dislocation-driven growth. On the basis of these observations, we suggest a
      formation mechanism of stacking faults that originate from dislocation voids
      during the cooling process in the syntheses. Similar stacking fault features were
      also observed in other NWs with WZ structure, such as cadmium sulfide (CdS) and
      zinc oxide (ZnO). 

PMID- 24295226
TI  - Plasma IL-25 is elevated in a subgroup of patients with clinical reactivity to
      peanut.
AB  - BACKGROUND: One of the IL-17 family members, IL-25, has been implicated with the
      initiation and amplification of Th2 responses in animal models and has been
      associated with airway hyper-reactivity. The involvement of IL-25 and also IL-17
      in food allergic disease remains to be investigated. FINDINGS: In this study
      thirty children suspected of peanut allergic disease underwent a double-blind
      placebo controlled food challenge (DBPCFC) and IL-25 and IL-17 plasma levels were
      determined before and after challenge. IL-25 was highly elevated only in subgroup
      of children with a positive DBPCFC outcome. Plasma IL-25 was absent in children
      with a negative DBPCFC outcome and in healthy controls. CONCLUSIONS: This study
      shows that IL-25, an IL-17 family member, is highly elevated only in children
      with a clinical response to peanut. This suggests a role for IL-25 in the
      pathogenesis of peanut allergy and elevated plasma IL-25 may be a sign of a
      severe atopic phenotype.

PMID- 24295228
TI  - Enhanced solid-state order and field-effect hole mobility through control of
      nanoscale polymer aggregation.
AB  - Efficient charge carrier transport in organic field-effect transistors (OFETs)
      often requires thin films that display long-range order and close pi-pi packing
      that is oriented in-plane with the substrate. Although some polymers have
      achieved high field-effect mobility with such solid-state properties, there are
      currently few general strategies for controlling the orientation of pi-stacking
      within polymer films. In order to probe structural effects on polymer-packing
      alignment, furan-containing diketopyrrolopyrrole (DPP) polymers with similar
      optoelectronic properties were synthesized with either linear hexadecyl or
      branched 2-butyloctyl side chains. Differences in polymer solubility were
      observed and attributed to variation in side-chain shape and polymer backbone
      curvature. Averaged field-effect hole mobilities of the polymers range from 0.19
      to 1.82 cm(2)/V.s, where PDPP3F-C16 is the least soluble polymer and provides the
      highest maximum mobility of 2.25 cm(2)/V.s. Analysis of the films by AFM and GIXD
      reveal that less soluble polymers with linear side chains exhibit larger
      crystalline domains, pack considerably more closely, and align with a greater
      preference for in-plane pi-pi packing. Characterization of the polymer solutions
      prior to spin-coating shows a correlation between early onset nanoscale
      aggregation and the formation of films with highly oriented in-plane pi-stacking.
      This effect is further observed when nonsolvent is added to PDPP3F-BO solutions
      to induce aggregation, which results in films with increased nanostructural
      order, in-plane pi-pi orientation, and field-effect hole mobilities. Since nearly
      all pi-conjugated materials may be coaxed to aggregate, this strategy for
      enhancing solid-state properties and OFET performance has applicability to a wide
      variety of organic electronic materials. 

PMID- 24295229
TI  - Measurements of the sensitivity of aerosol hygroscopicity and the kappa parameter
      to the O/C ratio.
AB  - We report measurements of the subsaturated hygroscopic growth of aerosol
      particles composed of single organic components of varying oxygen-to-carbon ratio
      up to relative humidities approaching saturation using the techniques of aerosol
      optical tweezers and an electrodynamic balance. The variation in the
      hygroscopicity parameter kappa between compounds of even the same O/C ratio is
      found to be significant with, for example, a range in kappa values from 0.12 to
      0.38 for compounds with an O/C of 1. The measurements are compared with a review
      of all of the available literature data for which both the kappa value and O/C
      ratio are reported, and a new parametrization is determined. Critical
      supersaturations predicted using this parametrization yield values that have
      associated uncertainties that are comparable to typical uncertainties in
      experimental measurements of critical supersaturations. However, the systematic
      variability between kappa parametrizations determined from different studies
      remains large, consistent with the O/C ratio providing only an approximate guide
      to aerosol hygroscopicity and reflecting significant variations for aerosols of
      different chemical functionality, composition, and oxidation history. 

PMID- 24295227
TI  - Recognition of pulmonary hypertension in the rheumatology community: lessons from
      a Quality Enhancement Research Initiative.
AB  - OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research
      Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived
      gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with
      systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc
      (aged >= 18 years) and provided data on a panel of diagnostic tests over 3 years.
      Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal
      pro-brain natriuretic peptide assays, high-resolution computed tomography of the
      lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when
      appropriate) were emphasised. Exclusion criteria included previously documented
      PAH, interstitial lung disease, and SSc overlapping with other connective tissue
      disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc
      (90% female; 80% white), with a median age of 57 years and median disease
      duration of 5 years. A total of 82% of patients were classified as New York Heart
      Association functional class I and II; of these patients, 177 had an
      echocardiogram at enrolment and 191 at any time during the study. Of those who
      met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent
      RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients
      with mild impairment. Although specific tools were recommended for screening PAH
      in patients with SSc, results indicate that significant diagnostic care gaps
      still exist in the general rheumatology community. Better understanding and
      adherence to guidelines could improve the care and, ideally, outcomes of these
      high-risk patients.

PMID- 24295230
TI  - Lipid profiling of follicular fluid from women undergoing IVF: young poor ovarian
      responders versus normal responders.
AB  - This study identified possible lipid biomarkers in follicular fluid from women
      with poor ovarian response. These biomarkers indicate pathophysiological pathways
      and have potential diagnostic applications. An observational case-control study
      of young women undergoing ovarian stimulation for in-vitro fertilization was
      conducted. The participants were categorized into a poor ovarian response group
      and a normal ovarian response to stimulation group. All of the women underwent
      the same ovarian stimulation protocol, and follicular fluid was collected after
      ovarian aspiration. Analyses were performed using matrix-assisted laser
      desorption/ionization mass spectrometry. Principal component analysis and Volcano
      plots were used to describe follicular fluid classification models based on the
      lipid profiles. A total of 10 lipids were differentially expressed between the
      study and control groups. Of these lipid ions, three belonged to the
      phosphatidylcholine subclass and were present in higher concentrations in the
      control group. The other seven differential lipids were present in the study
      group and classified into four lipid subclasses: phosphatidylethanolamines,
      phosphatidylglycerols, phosphatidylinositols, and diacylglycerols. These
      distinctive lipids may be involved in hormonal responses and oocyte development
      processes and may be useful as biomarkers for therapeutic intervention in women
      with poor ovarian response.

PMID- 24295233
TI  - Therapeutic collaboration and resistance: describing the nature and quality of
      the therapeutic relationship within ambivalence events using the Therapeutic
      Collaboration Coding System.
AB  - OBJECTIVES: We understand ambivalence as a cyclical movement between two opposing
      parts of the self. The emergence of a novel part produces an innovative moment,
      challenging the current maladaptive self-narrative. However, the novel part is
      subsequently attenuated by a return to the maladaptive self-narrative. This study
      focused on the analysis of the therapeutic collaboration in episodes in which a
      relatively poor-outcome client in narrative therapy expressed ambivalence.
      METHOD: For our analysis we used the Therapeutic Collaboration Coding System,
      developed to assess whether and how the therapeutic dyad is working within the
      therapeutic zone of proximal development (TZPD). RESULTS: Results showed that
      when the therapist challenged the client after the emergence of ambivalence, the
      client tended to invalidate (reject or ignore) the therapist's intervention.
      CONCLUSIONS: This suggests that in such ambivalence episodes the therapist did
      not match the client's developmental level, and by working outside the TZPD
      unintentionally contributed to the maintaining the client's ambivalence.

PMID- 24295235
TI  - Bifactor analysis and construct validity of the HADS: a cross-sectional and
      longitudinal study in fibromyalgia patients.
AB  - The dimensionality of the Hospital Anxiety and Depression Scale (HADS) is a
      current source of controversy among experts. The present study integrates a solid
      theoretical framework (Clark & Watson's, 1991, tripartite theory) and a fine
      grained methodological approach (structural equation modeling; SEM) to examine
      the dimensionality and construct validity of the HADS in fibromyalgia (FM)
      patients. Using the HADS data of 269 Spanish patients with FM, we estimated the
      cross-sectional and, for the first time, longitudinal fit (autoregressive model)
      of 2 competing models (oblique 2-factor vs. bifactor) via confirmatory factor
      analysis. The pattern of relationships between the HADS latent dimensions and
      positive and negative affect (PA and NA) was analyzed using SEM. HADS reliability
      was assessed by computing the omega and omega hierarchical coefficients. The
      bifactor model, which accounted for the covariance among HADS items with regard
      to 1 general factor (psychological distress) and 2 specific factors (depression
      and anxiety), described the HADS structure better than the original oblique 2
      factor model during both study periods. All latent dimensions of the bifactor
      model were temporally stable. The SEM analysis revealed a significant link
      between psychological distress and NA as well as between depression and low PA.
      Only the general factor of psychological distress showed adequate reliability. In
      conclusion, the HADS shows a clear bifactor structure among FM patients. Our
      results indicate that it is not recommendable to compute anxiety and depression
      scores separately because anxiety variance is tapped primarily by the broader
      construct of psychological distress, and both specific dimensions show low
      reliability.

PMID- 24295234
TI  - Complex gene expression in the dragline silk producing glands of the Western
      black widow (Latrodectus hesperus).
AB  - BACKGROUND: Orb-web and cob-web weaving spiders spin dragline silk fibers that
      are among the strongest materials known. Draglines are primarily composed of
      MaSp1 and MaSp2, two spidroins (spider fibrous proteins) expressed in the major
      ampullate (MA) silk glands. Prior genetic studies of dragline silk have focused
      mostly on determining the sequence of these spidroins, leaving other genetic
      aspects of silk synthesis largely uncharacterized. RESULTS: Here, we used deep
      sequencing to profile gene expression patterns in the Western black widow,
      Latrodectus hesperus. We sequenced millions of 3'-anchored "tags" of cDNAs
      derived either from MA glands or control tissue (cephalothorax) mRNAs, then
      associated the tags with genes by compiling a reference database from our newly
      constructed normalized L. hesperus cDNA library and published L. hesperus
      sequences. We were able to determine transcript abundance and alternative
      polyadenylation of each of three loci encoding MaSp1. The ratio of MaSp1:MaSp2
      transcripts varied between individuals, but on average was similar to the
      estimated ratio of MaSp1:MaSp2 in dragline fibers. We also identified
      transcription of TuSp1 in MA glands, another spidroin family member that encodes
      the primary component of egg-sac silk, synthesized in tubuliform glands. In
      addition to the spidroin paralogs, we identified 30 genes that are more
      abundantly represented in MA glands than cephalothoraxes and represent new
      candidates for involvement in spider silk synthesis. CONCLUSIONS: Modulating
      expression rates of MaSp1 variants as well as MaSp2 and TuSp1 could lead to
      differences in mechanical properties of dragline fibers. Many of the newly
      identified candidate genes likely encode secreted proteins, suggesting they could
      be incorporated into dragline fibers or assist in protein processing and fiber
      assembly. Our results demonstrate previously unrecognized transcript complexity
      in spider silk glands.

PMID- 24295236
TI  - Differentiating bipolar disorder from unipolar depression and ADHD: the utility
      of the general behavior inventory.
AB  - Adolescence and early adulthood are the peak ages for the onset of unipolar and
      bipolar mood disorders. Moreover, for most individuals with attention
      deficit/hyperactivity disorder (ADHD), symptoms and impairment begin in childhood
      but persist well into adolescence and adulthood (e.g., Barkley, 2010). Thus,
      adolescence and early adulthood represent a developmental window wherein
      individuals can be affected by mood disorders, ADHD, or both. Because treatment
      protocols for unipolar depression (UPD), bipolar disorder (BD), and ADHD are
      quite different, it is crucial that assessment instruments used among adolescents
      and young adults differentiate between these disorders. The primary objectives of
      this study were to evaluate the predictive and diagnostic validity of General
      Behavior Inventory (GBI; Depue et al., 1981) scores in discriminating BD from UPD
      and ADHD. Participants were drawn from adolescent (n = 361) and young adult (n =
      614) samples. Based on findings from logistic regression and receiver-operating
      characteristics analyses, the diagnostic efficiency of the GBI scales range from
      fair (discriminating UPD from BD) to good (discriminating BD participants from
      nonclinical controls). Multilevel diagnostic likelihood ratios are also provided
      to facilitate individual decision making.

PMID- 24295238
TI  - Introducing the Geneva emotion recognition test: an example of Rasch-based test
      development.
AB  - Existing tests to measure the ability to recognize other people's emotional
      expressions (emotion recognition ability [ERA]) mostly focus on a single modality
      (usually the face) and include only a small number of emotions, restricting their
      ecological validity. Further, their reliability is often unsatisfactory. The goal
      of the present study was to develop a new ERA test (Geneva Emotion Recognition
      Test [GERT]) that (a) features dynamic and multimodal actor portrayals (short
      videos with sound), (b) contains a large number of emotions, and (c) is based on
      modern psychometric principles (item response theory). We asked 295 participants
      to watch 108 actor portrayals and to choose, for each portrayal, which of 14
      emotions had been expressed by the actor. We then applied the Rasch model
      independently to each of the 14 emotion portrayal subsets to select 83 final
      items for the GERT. Results showed that the model fits the emotion subtests and
      the overall GERT and that measurement precision is satisfactory. Consistent with
      previous findings, we found a decline in ERA with increasing age and an ERA
      advantage for women. To conclude, the GERT is a promising instrument to measure
      ERA in a more ecologically valid and comprehensive fashion than previous tests.

PMID- 24295237
TI  - A psychometric evaluation of the panic disorder severity scale for children and
      adolescents.
AB  - The Panic Disorder Severity Scale (PDSS; Shear et al., 1997) is a well-validated
      measure that assesses symptoms of panic disorder with or without agoraphobia
      (PDA) in adults. The Panic Disorder Severity Scale for Children (PDSS-C) is an
      adaptation of the PDSS for youth ages 11-17. The current study evaluated the
      psychometric properties of the PDSS-C. Participants included 60 adolescents from
      a randomized controlled trial investigating the efficacy of an intensive
      cognitive behavioral treatment (CBT) for adolescent PDA. Convergent and
      discriminant validity of PDSS-C scores were evaluated via observed associations
      between the PDSS-C and the Childhood Anxiety Sensitivity Index (CASI; Silverman,
      Fleisig, Rabian, & Peterson, 1991), Multidimensional Anxiety Scale for Children
      (MASC; March, Parker, Sullivan, Stallings, & Conners, 1997), and Children's
      Depression Inventory (CDI; Kovacs, 2003). Baseline and posttreatment data
      afforded the opportunity to evaluate the measure's sensitivity to treatment
      related change. PDSS-C scores demonstrated acceptable internal consistency (alpha
      = .82) and adequate 1-day test-retest reliability (r = .79). Convergent and
      discriminant validity of the PDSS-C scores were supported through significant
      associations with the CASI and the MASC, and nonsignificant associations with the
      CDI, respectively. Linear regression analysis demonstrated sensitivity to
      treatment-related changes-that is, greater PDSS-C change scores were
      significantly associated with assignment to CBT vs. waitlist condition. Clinical
      utility was further established through significant associations between PDSS-C
      change scores and MASC and CASI change scores, and through nonsignificant
      associations with CDI change scores. Results support the use of PDSS-C scores as
      reliable, valid, and clinically useful for the assessment of youth panic disorder
      in research and clinical settings.

PMID- 24295239
TI  - A critical role of Fas-associated protein with death domain phosphorylation in
      intracellular reactive oxygen species homeostasis and aging.
AB  - AIM: Reactive oxygen species (ROS) plays important roles in aging. However, the
      specific mechanisms for intracellular ROS accumulation, especially during aging,
      remain elusive. RESULTS: We have reported that Fas-associated protein with death
      domain (FADD) phosphorylation abolishes the recruitment of phosphatase type 2A C
      subunit (PP2Ac) to protein kinase C (PKC)betaII, which specifically regulates
      mitochondrial ROS generation by p66shc. Here, we have studied the role of FADD
      phosphorylation in an FADD constitutive-phosphorylation mutation (FADD-D) mouse
      model. In FADD-D mice, the constitutive FADD phosphorylation led to ROS
      accumulation (hydrogen peroxide [H2O2]), in a process that was dependent on
      PKCbeta and accompanied by increased PKCbeta and p66shc phosphorylation, impaired
      mitochondrial integrity, and enhanced sensitivity to oxidative stress-mediated
      apoptosis. Moreover, FADD-D mice exhibited premature aging-like phenotypes,
      including DNA damage, cellular senescence, and shortened lifespan. In addition,
      we demonstrate that FADD phosphorylation and the recruitment of PP2A and FADD to
      PKCbeta are induced responses to oxidative stress, and that the extent of FADD
      phosphorylation in wild-type mice was augmented during aging, accompanied by
      impairment of the interaction between PKCbeta and PP2A. INNOVATION: The present
      study first addresses the role of FADD phosphorylation in aging through
      controlling mitochondrial ROS specifically generated by PKCbeta. CONCLUSION:
      These data identify that FADD phosphorylation is critical for the PKCbeta-p66shc
      signaling route to generate H2O2 and to implicate enhanced FADD phosphorylation
      as a primary cause of ROS accumulation during aging.

PMID- 24295241
TI  - Evaluation of a case-based urology learning program.
AB  - OBJECTIVE: To address the challenges that today's trainees encounter, such as
      information overload and reduced immersion in the field, and recognizing their
      preference for novel educational resources, an electronic case-based urology
      learning program was developed. Each case was designed to illustrate the basic
      principles of the disease process and the fundamentals of evaluation and
      management using the Socratic method, recapitulating a prototypical patient
      encounter. METHODS: A 21-question survey was developed after review of published
      reports of classroom and clinical learning environment surveys. The target group
      was 2 pilot urology training programs (the Cleveland Clinic and University
      Hospitals-Case Medical Center). The responses were entirely anonymous. RESULTS: A
      total of 32 trainees participated (8 fellows and 24 residents), representing a
      53% response rate. Most trainees (79%) were able to process cases within an
      average of <= 10 minutes. Of the trainees, 91% reported referring back to
      particular cases for patient care, to review for examinations, or for studying.
      Most trainees believed a case-based urology learning program would be a
      potentially important resource for clinical practice (69%) and for preparing for
      the in-service (63%) or board (69%) examinations. Most trainees believed the
      program met its goals of illustrating the basics principles of the disease
      process (88%), outlining the fundamentals of evaluation and management (94%), and
      improving the trainees' knowledge base (91%). CONCLUSION: An electronic case
      based urology learning program is feasible and useful and stimulates learning at
      all trainee levels.

PMID- 24295240
TI  - Livin expression is an independent factor in rectal cancer patients with or
      without preoperative radiotherapy.
AB  - BACKGROUND: This study was aimed to investigate the expression significance of
      Livin in relation to radiotherapy (RT), clinicopathological and biological
      factors of rectal cancer patients. METHODS: This study included 144 primary
      rectal cancer patients who participated in a Swedish clinical trial of
      preoperative radiotherapy. Tissue microarray samples from the excised primary
      rectal cancers, normal mucosa and lymph node metastases were immunostained with
      Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was
      assayed after Livin knock-down. RESULTS: The expression of Livin was
      significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal
      mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin
      negative and positive tumors died at 180 months after surgery, and the difference
      tended to be statistically significant (P = 0.091). In multivariate analyses, the
      difference achieved statistical significance, independent of TNM stage, local and
      distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09,
      95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells
      with Livin knock-down exhibited decreased proliferation compared with controls
      after RT. CONCLUSIONS: The expression of Livin was was independently related to
      survival in rectal cancer patients, suggesting Livin as a useful prognostic
      factor for rectal cancer patients.

PMID- 24295242
TI  - Improving access to urologic care for rural populations through outreach clinics.
AB  - OBJECTIVE: To determine the effect of outreach clinics on access to urologic care
      in a state with a large rural population. This is especially pertinent given the
      predicted shortage of urologists over the next decade and the trend toward
      practice in urban area. METHODS: We analyzed provider level data from urologic
      practices within the state of Iowa using information from 2 publicly available
      sources: (1) the Office of Statewide (Iowa) Clinical Education Programs, which
      collects detailed information on visiting consultant urologists (VCU), and (2)
      the Iowa Physician Information System, which tracks demographic and professional
      data on all active physicians in Iowa. Factors analyzed included percent of
      counties and Iowans served by urologists and travel distances/times for patients
      and physicians. RESULTS: Currently, 57% of Iowans are within 30 minutes of a
      urologist's primary office, increasing to 84% with VCU outreach clinics. Fifty
      five urologists, including 40 of 69 (58%) of Iowa-based urologists, perform
      outreach within Iowa, accounting for 198 clinic days and 20,400 miles of travel
      per month. CONCLUSION: Within Iowa, the lack of rural urologists has been
      mitigated, in part, by an extensive VCU network. However, improved access has
      required significant effort from urologists in both time and miles traveled. This
      study is the first to show how a rural state can effectively use physician
      outreach clinics to provide specialized urologic care to underserved, rural
      communities.

PMID- 24295243
TI  - Editorial comment.

PMID- 24295244
TI  - Reply: To PMID 24295242.

PMID- 24295246
TI  - Reply: To PMID 24295245.

PMID- 24295245
TI  - National trends in the utilization of partial nephrectomy before and after the
      establishment of AUA guidelines for the management of renal masses.
AB  - OBJECTIVE: To assess the impact of the American Urological Association (AUA)
      guidelines advocating partial nephrectomy for T1 tumors guidelines on the
      likelihood of undergoing partial nephrectomy. MATERIALS AND METHODS: We analyzed
      the Nationwide Inpatient Sample (NIS), a dataset encompassing 20% of all United
      States inpatient hospitalizations, from 2007 through 2010. Our dependent variable
      was receipt of radical vs partial nephrectomy (55.50, 55.51, 55.52, and 55.54 vs
      55.4) for a renal mass (International Classification of Disease, 9th Revision
      [ICD-9] code 189.0). The independent variable of interest was time of surgery
      (before or after the establishment of AUA guidelines); covariates included a
      diagnosis of chronic kidney disease (CKD), overall comorbidity, age, race,
      gender, geographic region, income, and hospital characteristics. Bivariate and
      multivariable adjusted logistic regression was used to determine the association
      between receipt of partial nephrectomy and time of guideline establishment.
      RESULTS: We identified 26,165 patients with renal tumors who underwent surgery.
      Before the guidelines, 4031 patients (27%) underwent partial nephrectomy compared
      to 3559 (32%) after. On multivariable analysis, undergoing surgery after the
      establishment of guidelines (odds ratio [OR] 1.20, 95% confidence interval [CI]
      1.08-1.32, P <.01) was an independent predictor of partial nephrectomy. Other
      factors associated with partial nephrectomy were urban location, surgery at a
      teaching hospital, large hospital bed size, Northeast location, and Black race.
      Female gender and CKD were not associated with partial nephrectomy. CONCLUSION:
      Although adoption of partial nephrectomy increased after establishment of new
      guidelines on renal masses, partial nephrectomy remains an underutilized
      procedure. Future research must focus on barriers to adoption of partial
      nephrectomy and how to overcome them.

PMID- 24295247
TI  - Editorial comment.

PMID- 24295248
TI  - Robotic-assisted radical cystectomy with extracorporeal urinary diversion for
      urothelial carcinoma of the bladder: analysis of complications and oncologic
      outcomes in 175 patients with a median follow-up of 3 years.
AB  - OBJECTIVE: To report oncologic outcomes and complications after robotic-assisted
      radical cystectomy (RARC). MATERIALS AND METHODS: From March 2004 to August 2011,
      175 consecutive patients underwent RARC with extracorporeal urinary diversion at
      our institution by a single surgeon. The study design was prospective.
      Perioperative parameters and postoperative complications were prospectively
      collected using the modified Clavien system. Recurrence-free survival and cancer
      specific survival curves were generated using the Kaplan-Meier method. RESULTS: A
      total of 145 men and 30 women with a median age of 73 years and a median body
      mass index of 27 kg/m(2) underwent RARC. Four patients (2.3%) required conversion
      to open surgery because of difficulty to progress. One hundred nine patients
      (62%) underwent a transcutaneous ileal conduit, 40 patients (23%) an orthotopic
      neobladder, and 26 (15%) a continent cutaneous conduit. The median operating time
      was 360 minutes (interquartile range [IQR]: 300-420). The median estimated blood
      loss was 400 mL (IQR: 250-612), with a transfusion rate of 17.0%. The median
      postoperative length of stay was 7.0 days (IQR: 5.2-10). Early (<30 days) and
      late surgery-related complications (30-90 days) occurred in 74 (42%) and 59 (34%)
      patients, respectively. The perioperative mortality rate was 2.8%. The positive
      soft tissue surgical margins rate was 5%. The median number of lymph nodes
      removed was 19 (IQR: 12-28). The median follow-up was 37 months (IQR: 21.5-53.5).
      Actuarial recurrence-free survival and cancer-specific survival at 2, 3, and 5
      years after RARC were 67%, 63%, 63% and 73%, 68%, 66%, respectively. CONCLUSION:
      RARC achieved mid-term oncologic efficacy. Moreover, the complication rates were
      comparable with open radical cystectomy series.

PMID- 24295249
TI  - Editorial comment.

PMID- 24295250
TI  - Erectile dysfunction and fruit/vegetable consumption among diabetic Canadian men.
AB  - OBJECTIVE: To evaluate the association between fruit/vegetable consumption and
      erectile dysfunction (ED) among Canadian men with diabetes. METHODS: Data from
      the 2011 Survey on Living with Chronic Diseases in Canada - Diabetes Component
      were analyzed using Statistical Analysis System Enterprise Guide (SAS EG).
      Respondents were asked a series questions related to their sociodemographics,
      lifestyle, and chronic health conditions. The association between fruit/vegetable
      consumption and ED was examined using logistic regression after controlling for
      potential confounding factors. Bootstrap procedure was used to estimate sample
      distribution and calculate confidence intervals. RESULTS: Overall, 26.2% of
      respondents reported having ED. The prevalence increased with age and duration of
      diabetes. Compared with respondents without ED, those with ED were more likely to
      be obese, smokers, physically inactive, and either divorced, widowed, or
      separated. Diabetes complications such as nerve damage, circulation problems, and
      kidney failure or kidney disease were also significantly associated with ED.
      After controlling for potential confounding factors, a 10% risk reduction of ED
      was found with each additional daily serving of fruit/vegetable consumed.
      CONCLUSION: ED is common among Canadian men with diabetes. ED was highly
      associated with age, duration of diabetes, obesity, smoking, and the presence of
      other diabetes-related complications. Fruit and vegetable consumption might have
      a protective effect against ED.

PMID- 24295251
TI  - Correlation between serum prostate specific antigen level and prostate volume in
      a community-based cohort: large-scale screening of 35,223 Korean men.
AB  - OBJECTIVE: To investigate the relationship between prostate specific antigen
      (PSA) level and prostate volume (PV) according to age in a community-based
      population of Korean men enrolled in a large-scale screening program. METHODS: A
      total of 35,223 men who enrolled in the Korean Prostate Health Council Screening
      Program from January 2001 to December 2011 were included in this study. Patients
      with a serum PSA level of >10 ng/mL or younger than 40 years were excluded. We
      analyzed PSA level and PV as measured through transrectal ultrasonography
      according to stratified age cohorts. We used Pearson correlation and linear
      regression analysis according to age to describe the correlation between PSA
      level and PV. RESULTS: Mean PSA level and mean PV increased significantly with
      age (all P values <.001). Based on data from 5 age cohorts, mean PSA level
      increased about 0.3 ng/mL every 10 years and mean PV increased about 3 mL every
      10 years. The slope of the linear regression between PSA level and PV was 4.582,
      and the slope of the linear regression increased with age. We derived equations
      relating PSA level and PV for the various age cohorts. CONCLUSION: Based on a
      large-scale health screening program, we derived equations relating PSA level to
      PV according to age group. These data provide a baseline for the normal
      population by avoiding the interventional bias of urinary symptoms, in contrast
      to previous data derived from patients who visited hospitals because of prostate
      related health concerns.

PMID- 24295252
TI  - Editorial comment.

PMID- 24295253
TI  - Gender-related fetal development of the internal urethral sphincter.
AB  - OBJECTIVE: To investigate the fetal development of the internal urethral
      sphincter and the gender-related morphologic differences of the bladder outlet.
      MATERIALS AND METHODS: Thirty-seven (14 female, 23 male) fetal bladder neck
      specimens (mean gestational age, 19.4 weeks) with the smooth muscle complex of
      the internal sphincter were investigated histologically. After immunostaining
      serial sections in 3 reference planes (sagittal, frontal, and horizontal) of the
      bladder neck, the internal sphincter volumes and bladder outlet diameters were
      measured and correlated with gender and age of gestation. RESULTS: Between the
      18th and 40th week of gestation, an exponential growth of the internal sphincter
      muscle with significant higher volumes could be observed in male fetuses compared
      with female fetuses (internal sphincter volumes, P = .006; radius of the
      sphincter complex, P = .001). As a result of this gender difference, the bladder
      outlet was significantly (P = .001) narrower in male than in female fetuses.
      Moreover, we found a significant positive correlation between age and all
      measured parameters in both male and female specimens. CONCLUSION: The present
      study indicates a significant closer bladder outlet in male fetuses compared than
      in females. It thereby provides evidence of a gender-related functional
      obstruction in addition to a suppositious transient infravesical obstruction in
      male human fetuses.

PMID- 24295254
TI  - Editorial comment.

PMID- 24295255
TI  - Reply: To PMID 24295253.

PMID- 24295256
TI  - Artificial urinary sphincter revision: the role of ultrasound.
AB  - OBJECTIVE: To assess the accuracy of office-based ultrasound (US) to identify the
      fluid status of the AMS 800 artificial urinary sphincter (AUS) pressure
      regulating balloon (PRB). METHODS: Patients who underwent AUS revision surgery
      (removal/replacement) from January 4, 2007, to January 4, 2010, were identified.
      US were done preoperatively to assess the system fluid status. Intraoperative
      findings were recorded. Sensitivity and specificity were calculated comparing US
      results with intra-/postoperative findings. When the PRB was underfilled, the
      location of the device fluid leak was determined, and the device was
      removed/replaced. In cases of a full PRB, patients had a cuff downsizing or total
      removal/replacement. RESULTS: A total of 27 patients were identified. Reasons for
      not obtaining US included: advanced device age (4), cuff erosion (2), volume
      determination by other modality (2), cuff site pain (1), isolated pump
      malfunctions (1), and other (3). Fourteen patients underwent an US before the
      removal/replacement. By US, PRB was full (21-23 mL) in 43% of the patients and
      empty/underfilled (0-6 mL) in 57%. US was 100% sensitive and specific determining
      fluid status. When PRB was full, management consisted of cuff downsizing (3),
      transcorporal cuff placement (1), and total removal/replacement (2). In all cases
      of device leak, an entire removal/replacement was performed. The cuff was
      identified as the site of leak in 50% of cases. CONCLUSION: US is an effective
      and accurate way of determining the fluid status of the AMS 800 AUS. Given the
      accuracy of this modality, the system can be filled with saline solution without
      losing the ability to determine fluid status.

PMID- 24295257
TI  - Editorial comment.

PMID- 24295258
TI  - Reply: To PMID 24295256.

PMID- 24295259
TI  - Re: Pshak et al.: Is tissue interposition always necessary in transvaginal repair
      of benign, recurrent vesicovaginal fistulae? (Urology 2013;82:707-712).

PMID- 24295260
TI  - Reply by the authors.

PMID- 24295261
TI  - Re: Bastab et al.: Randomized clinical trial comparing effectiveness of
      intracorpus spongiosum block versus topical anesthesia for performing visual
      internal urethrotomy for urethral stricture disease (Urology 2013;81:204-207).

PMID- 24295262
TI  - Re: Mistry et al.: A simple two-stage "Bailout" technique for the removal of an
      unyielding ureteric stent (Urology 2013;82:242-244).

PMID- 24295263
TI  - Pharmacologic characterization of human male urethral smooth muscle: an in vitro
      approach.
AB  - OBJECTIVE: To elucidate the functional responses of isolated human urethral
      smooth muscle to various agents known to exert smooth muscle contraction or
      relaxation. METHODS: Specimens of penile urethra were obtained from male patients
      who had undergone male-to-female gender reassignment surgery. Using the tissue
      bath technique, the contraction induced by increasing concentrations (1 nM-10
      MUM) of norepinephrine, phenylephrine, acetylcholine, carbachol, prostaglandin
      F2alpha, endothelin 1, angiotensin II, and oxytocin was measured. In another set
      up, the effects of C-type natriuretic peptide (0.1 nM-1 MUM), sodium
      nitroprusside, sildenafil, forskolin, alpha2-antagonist delquamine, and
      acetylcholine (1 nM/10 nM-10 MUM) on the tension induced by norepinephrine were
      investigated. The production of cyclic guanosine monophosphate (GMP) and cyclic
      adenosine monophosphate (AMP) was measured by means of specific
      radioimmunoassays. RESULTS: Endothelin 1, oxytocin, prostaglandin F2alpha,
      norepinephrine, and phenylephrine induced dose-dependent contraction of the
      isolated urethral tissue, whereas acetylcholine, carbachol, and angiotensin II
      had no or only minor contractile effects. The contraction induced by
      norepinephrine was reversed by the drugs with the following rank order of
      efficacy: sodium nitroprusside > delquamine > sildenafil > C-type natriuretic
      peptide > forskolin > acetylcholine. The maximal reversion of tension ranged from
      68% (sodium nitroprusside) to 22% (acetylcholine). The relaxing effects of the
      drugs were paralleled by a several-fold increase in tissue levels of cyclic GMP
      and cyclic adenosine monophosphate. CONCLUSION: The results provide evidence that
      urethral smooth muscle is under the control of endogenous compounds, such as
      adrenergic agonists (norepinephrine and phenylephrine), vasoactive peptides,
      prostagladins, NO/cyclic GMP, and acetylcholine, assumed to influence micturition
      at the peripheral level.

PMID- 24295264
TI  - Activation of extrinsic apoptotic pathway from bladder biopsy in patients with
      interstitial cystitis/painful bladder syndrome.
AB  - OBJECTIVE: To investigate the intrinsic or extrinsic pathway of apoptosis from
      bladder biopsy that was performed in interstitial cystitis/painful bladder
      syndrome (IC/PBS). Although previous studies have reported observations of the
      dysfunction, denudation, and thinning of the bladder urothelium in patients
      associated with an increase of cell apoptosis, the molecular mechanism is
      unclear. METHODS: The study group consisted of 32 patients with IC/PBS, and the
      control group consisted of 12 volunteers without any symptoms of IC. Bladder
      biopsies were obtained from both the groups. The expression of apoptosis
      associated proteins was observed by detecting the Bcl-2/Bax ratio and the levels
      of cleaved caspase-9, Fas, cleaved caspase-8, and cleaved caspase-3 to
      differentiate intrinsic or extrinsic pathway. The data were analyzed using Mann
      Whitney U test. RESULTS: Increased levels of cleaved caspase-3 were found in the
      IC/PBS group relative to the control group (P <.05). The levels of the extrinsic
      apoptotic pathway proteins, Fas and cleaved caspase-8, were also increased in the
      study group compared with the control group (P <.05). There was no significant
      difference in the levels of the intrinsic apoptotic pathway proteins, including
      cleaved caspase-9 and the Bcl-2/Bax ratio, between the control and study groups.
      CONCLUSION: Our findings demonstrate the activation of extrinsic apoptotic
      pathway from bladder biopsy in patients with IC/PBS. This study might help us to
      clarify the molecular changes and lead to a better understanding of this bladder
      disease.

PMID- 24295265
TI  - Down regulation of vascular endothelial growth factor is associated with
      decreased inflammation after intravesical OnabotulinumtoxinA injections combined
      with hydrodistention for patients with interstitial cystitis--clinical results
      and immunohistochemistry analysis.
AB  - OBJECTIVE: To measure the expression of vascular endothelial growth factor (VEGF)
      in bladder tissue and improvement of clinical symptoms and inflammatory
      biomarkers after repeated onabotulinumtoxinA injections in patients with
      interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Twenty-one
      patients with IC/BPS received 4 sets of intravesical 100-U onabotulinumtoxinA
      injections combined with hydrodistention. Assessments at baseline and 6 months
      after each treatment included O'Leary-Sant Symptom Score, bladder pain visual
      analog scale, functional bladder capacity (FBC), grade of glomerulations under
      cystoscopic hydrodistention, and urodynamic parameters. The bladder specimens at
      baseline and at the fourth treatment were investigated by western blotting for
      the expression of VEGF, Bcl-2-associated X protein (Bax), and phospho-p38 (p
      p38), and immunohistochemistry staining for apoptotic and mast cell activity. Six
      women with genuine stress urinary incontinence served as controls for comparison.
      RESULTS: The measured immunohistochemical parameters were significantly higher in
      patients with IC/BPS than the controls. Statistically significant decrease in the
      expression of VEGF was noted in patients treated with repeated onabotulinumtoxinA
      injections compared with baseline (0.83 +/- 0.28 vs 1.00; P = .016). The
      apoptotic cell count (0.86 +/- 1.00 vs 1.76 +/- 1.69; P = .026) and mast cell
      activity (1.81 +/- 2.29 vs 5.82 +/- 4.97; P = .009) were also reduced.
      Significant increases in FBC and global response assessment score were also
      observed after onabotulinumtoxinA treatment; however, except for mast cell
      activity, VEGF expression and apoptotic cell count were still significantly
      higher than the controls. CONCLUSION: Increased VEGF was associated with bladder
      inflammation and smaller FBC in patients with IC/BPS and decreased after repeated
      onabotulinumtoxinA injections and hydrodistention, suggesting VEGF plays an
      important role in the pathogenesis of IC/BPS.

PMID- 24295266
TI  - Inhibitor of 5-lipoxygenase, zileuton, suppresses prostate cancer metastasis by
      upregulating E-cadherin and paxillin.
AB  - OBJECTIVE: To investigate the expression of 5-lipoxygenase (5-LOX) in metastatic
      prostate cancer and whether zileuton, the inhibitor of 5-LOX, plays a role in the
      metastasis of prostate cancer. METHODS: An enzyme-linked immunosorbent assay was
      used to measure 5-hydroxyeicosatetraenoic acid (5-HETE) in patient and TRAMP mice
      blood samples. Kaplan-Meier analysis and the log-rank test were used to analyze
      the survival of the mice. Immunofluorescence and immunohistochemistry were used
      to assay the expression of 5-LOX in the samples. After treatment with 10 MUM
      zileuton, cell motility and the invasion of PC-3 cells were assayed using
      immunofluorescence, Western blotting, and transwell. TRAMP mice were treated with
      zileuton (600 mg/kg and 1200 mg/kg) at 24 weeks of age. Ten weeks later, the mice
      were killed, and the tumors (size and number) were measured. RESULTS: The levels
      of 5-HETE were significantly greater in the TRAMP mice with metastasis than in
      the tumors in situ. However, no such difference was found in the human samples.
      The lifespan of the mice was shorter at high levels of 5-HETE (>2.4 ng/mL). The
      expression of 5-LOX in the metastasis sample was notably greater than that in the
      tumors in situ. After treatment with zileuton, the expression of paxillin and E
      cadherin in PC-3 and LNCaP cells was upregulated. In the transwell experiments,
      the motility of PC-3 was suppressed after treatment with zileuton. The mice
      treated with a high level of zileuton (1200 mg/kg) also had fewer tumors;
      however, the size did not show a significant difference. CONCLUSION: The
      inhibitor of 5-LOX, zileuton, can suppress prostate cancer metastasis by repaired
      expression of E-cadherin and paxillin.

PMID- 24295267
TI  - Colovesical fistula caused by an ingested chicken bone.
AB  - Colovesical fistula involving the sigmoid colon is the most common fistulous
      communication between the gastrointestinal tract and the urinary bladder. These
      tracts are most commonly associated with diverticulitis but might arise secondary
      to a neoplasm, inflammatory bowel disease, iatrogenic injuries, radiation
      therapy, trauma, or foreign bodies. We describe a patient who developed a fistula
      between the sigmoid colon and bladder secondary to an ingested chicken bone that
      lodged in a colonic diverticulum. A portion of the foreign body was removed by
      direct visualization on colonoscopy; the remaining fragment passed spontaneously
      per urethra after hospital discharge. 

PMID- 24295268
TI  - Nephrolithiasis in "back-to-back" kidneys.
AB  - A 57-year-old woman presented with a 1-week history of left lower quadrant pain
      and nausea and vomiting. Computed tomography without contrast demonstrated a left
      2.3-cm calculus at the ureteropelvic junction and a 6-mm lower pole calculus. The
      kidneys were in the pelvis and oriented "back-to-back," with the lateral portions
      of the kidneys fused in the midline. To our knowledge, this is the first
      description of this renal fusion anomaly. The patient underwent robotic
      pyelolithotomy of the ureteropelvic junction calculus and subsequent flexible
      ureteroscopic laser lithotripsy of the lower pole calculus and ureteral stent
      placement through the assistant working port. 

PMID- 24295269
TI  - Retroperitoneal ganglioneuroma mimicking right adrenal mass.
AB  - Ganglioneuroma is a rare benign tumor of the sympathetic nervous system that can
      arise from the adrenal medulla. Few reports have been published of the surgical
      resection of this rare tumor using a laparoscopic approach. We present a case of
      retroperitoneal ganglioneuroma that mimicked an adrenal mass on imaging and was
      resected laparoscopically.

PMID- 24295270
TI  - Life-threatening urethral bleeding induced by a pseudoaneurysm of the obturator
      artery.
AB  - We report the case of a 56-year-old man who in a motor vehicle collision
      developed a pelvic fracture and complete urethra rupture. Sudden onset of
      intermittent severe urethral bleeding occurred and it led to life-threatening
      blood pressure drop and dyspnea. An angiography of internal iliac artery showed a
      pseudoaneurysm involving the right obturator artery. Super-selective embolization
      of the feeding vessel was performed with cessation of the blood flow immediately.

PMID- 24295271
TI  - Orbital solitary fibrous tumor: a case series with review of the literature.
AB  - PURPOSE: To report the clinical features, patient demographics, management, and
      outcomes of a series of patients with orbital solitary fibrous tumors (OSFTs) and
      provide a review of the English literature describing this rare entity. DESIGN: A
      review of patient demographics, clinical presentations, imaging, histopathology,
      surgical management, and outcomes were analyzed. METHODS: A non-comparative
      retrospective chart review of the demographics, clinical presentations, imaging,
      histopathological features, management, and disease outcomes of patients
      presenting to a tertiary orbital center with a tissue diagnosis of OSFT between
      2007-2012 was performed along with a review of the English-language literature.
      RESULTS: Our study included four male patients, with a mean age of 48 years at
      referral. The most common presentations included a slowly growing mass, globe
      displacement, diplopia on extreme gazes, and/or facial disfiguration. All tumors
      were analyzed with histopathology and immunohistochemistry. Treatment involved
      the complete surgical excision of the lesion, obtaining clear margins. All
      patients remain alive and well with no evidence of recurrence after a minimum
      follow-up of 15 months (range 15 months-5 years). CONCLUSION: SFTs should be
      considered when confronting a painless slowly growing orbital mass that induces
      globe displacement and/or facial deformity. Imaging will show a well-defined
      lesion that enhances with contrast. A careful initial surgical excision with
      clear margins is required for adequate local control of the tumor, avoiding
      recurrence and potential malignant transformation.

PMID- 24295272
TI  - An intricate relationship between pain and depression: clinical correlates,
      coactivation factors and therapeutic targets.
AB  - INTRODUCTION: An apparent clinical relationship between pain and depression has
      long been recognized, which makes an enormous impact on the individual health
      care. At present, the practical implication of such overlapping symptomatology
      between pain and depression is not clear, but the prevalence estimates for
      depression are substantially inflated among patients with chronic pain and vice
      versa. This interaction has been labeled as the depression-pain syndrome or
      depression-pain dyad. AREAS COVERED: This article discusses the neurobiological
      substrates and neuroanatomical pathways involved in pain-depression dyad along
      with newer therapeutic targets. EXPERT OPINION: Several key themes emerged from
      our review of the relationship between depression and pain. First, the diagnosis
      of depression in pain or vice versa is particularly challenging, and the
      development of better diagnostic framework that involves both pain and depression
      is particularly required. Secondly, the entwined relationship between pain and
      depression supports the possibility of common coactivating factors that results
      in their neurophysiological overlap. A broad understanding of the role played by
      the central nervous system (CNS) in the processing of pain and depression may
      eventually lead to the introduction of triple reuptake inhibitors, agomelatine,
      vilazodone and ketamine with novel mechanism of action, hence appear to be of
      promising potential for pain with depression.

PMID- 24295273
TI  - Problem-based learning (PBL): getting the most out of your students - their roles
      and responsibilities: AMEE Guide No. 84.
AB  - This Guide discusses the considerable literature on the merits or shortcomings of
      Problem-based learning (PBL), and the factors that promote or inhibit it, when
      seen through the eyes of the student. It seems to be the case that PBL works best
      when students and faculty understand the various factors that influence learning
      and are aware of their roles; this Guide deals with each of the main issues in
      turn. One of the most important concepts to recognise is that students and
      Faculty share the responsibility for learning and there are several factors that
      can influence its success. They include student motivation for PBL and the
      various ways in which they respond to being immersed in the process. As faculty,
      we also need to consider the way in which the learning environment supports the
      students develop the habit of life-long learning, and the skills and attitudes
      that will help them become competent reflective practitioners. Each of these
      elements place responsibilities upon the student, but also upon the Faculty and
      learning community they are joining. Although all of the authors work in a
      European setting, where PBL is used extensively as a learning strategy in many
      medical schools, the lessons learned we suggest, apply more widely, and several
      of the important factors apply to any form of curriculum. This Guide follows on
      from a previous review in the AMEE Guides in Medical education series, which
      provided an overview of PBL and attempts to emphasise the key role that students
      have in mastering their subject through PBL. This should render the business of
      being a student a little less mystifying, and help faculty to see how they can
      help their students acquire the independence and mastery that they will need. 

PMID- 24295274
TI  - Th1/Th2 polarization in tonsillar lymphocyte form patients with IgA nephropathy.
AB  - Imbalance of Th1/Th2 pro-inflammatory cytokines plays an important role in the
      development and progression of IgA nephropathy (IgAN). Clinical development and
      exacerbation of IgAN are frequently preceded by episodes of upper respiratory
      tract infection, and palatine tonsils represent the predominant immunocompetent
      tissue of the upper respiratory tract. This study examined tonsillar lymphocytes
      of IgAN who suffered from tonsillitis (n = 22), and using tonsils derived from
      patients with chronic tonsillitis (n = 24) but without renal disease as a
      control. We identified a polarization toward Th2 response in tonsils of IgAN
      patients. TH0 cells are differentially mobilized during contact sensitization and
      by adjuvants such as lipopolysaccharide (LPS) that induce T-helper type 1 (Th1)
      responses, or alpha-hemolytic streptococcus (HS) that induces T-helper type 2
      (Th2) responses. Th1:Th2 ratio is correlated with proteinuria and renal
      pathologic changes in IgAN group. Our study suggests that IgAN is associated with
      the change in Th1/Th2 balance in favor of Th2 lymphocytes.

PMID- 24295275
TI  - Thermodynamics and mechanism studies on electrochemical removal of cesium ions
      from aqueous solution using a nanoparticle film of copper hexacyanoferrate.
AB  - Nanoparticle (NPs) film of copper hexacyanoferrate (CuHCF(III)) was developed for
      electrochemically cesium separation from wastewater. Different form the electro-
      or chemical deposited films, CuHCF(III) NPs were firstly covered with
      ferrocyanide anions, so that they can be well dispersed in water and formed ink.
      Then CuHCF(III) NPs can be uniformly coated by simple wet printing methods, so it
      is feasible to prepare NPs film of any sizes, or any patterns at low cost. This
      process provided a promising technology for preparing large scale electrodes for
      sequential removal of Cs from wastewater in the columns. Cs separation can be
      controlled by an electrically switched ion exchange (ESIX) system. Effect of
      temperatures, and ionic strength on Cs removal was investigated. Thermodynamics
      results showed that Cs adsorption process was exothermic in nature and favored at
      low temperature. Ionic strength study indicated the CuHCF(III) film can
      selectively separate Cs in wide ionic strength range from 1 * 10(-4) to 1 * 10(
      1) M Na(+). XPS results demonstrated that the electrochemical oxidation-reduction
      of Fe (II/III) made contributions to Cs separation. 

PMID- 24295276
TI  - Social contagion of correct and incorrect information in memory.
AB  - The present study examines how discussion between individuals regarding a shared
      memory affects their subsequent individual memory reports. In three experiments
      pairs of participants recalled items from photographs of common household scenes,
      discussed their recall with each other, and then recalled the items again
      individually. Results showed that after the discussion. individuals recalled more
      correct items and more incorrect items, with very small non-significant
      increases, or no change, in recall accuracy. The information people were exposed
      to during the discussion was generally accurate, although not as accurate as
      individuals' initial recall. Individuals incorporated correct exposure items into
      their subsequent recall at a higher rate than incorrect exposure items.
      Participants who were initially more accurate became less accurate, and initially
      less-accurate participants became more accurate as a result of their discussion.
      Comparisons to no-discussion control groups suggest that the effects were not
      simply the product of repeated recall opportunities or self-cueing, but rather
      reflect the transmission of information between individuals. 

PMID- 24295278
TI  - Solvent or temperature induced diverse coordination polymers of silver(I) sulfate
      and bipyrazole systems: syntheses, crystal structures, luminescence, and sorption
      properties.
AB  - Three new coordination polymers, [Ag4(H2bpz)4(SO4)2].H2O (1),
      [Ag2(H2bpz)2(SO4)].3H2O (2), and [Ag3(H2bpz)4](SO4)2/3(OH)5/3.4H2O (3) have been
      solvothermally synthesized with Ag2SO4 and flexible ligand 3,3',5,5'-tetramethyl
      4,4'-bipyrazole (H2bpz) in different solvents and temperatures. Complex 1 is a 2
      fold interpenetrated three-dimensional (3D) framework with an uncommon (3,5)
      connected hms topology. Complex 2 is a structural isomer of 1 and shows a three
      connected 2D ths net consisting of interesting 3-fold and 2-fold heterochiral
      helical chains. Complex 3 discloses a grid layer structure, containing
      heterochiral helical chains and an unusual meso-helix. More interestingly, three
      sets of layers in 3 stack in different directions, affording an unprecedented 2D
      + 2D + 2D -> 3D polycatenating cationic framework with 1D + 3D porous systems. In
      1-3, H2bpz exhibit exobidentate bridging fashions with wide-ranged interpyrazole
      tilting angles and changeable coordination configurations, such as cis and trans
      fashions in 1 and 3 and uniform trans fashion in 2. These lead to the isomeric
      [Ag(H2bpz)]n arrays of wavelike and helical chains in 1 and 2, respectively.
      Complexes 1-3 display solid-state photoluminescence stemming from the ligand
      centered fluorescent emissions of H2bpz. Because of the highly polar framework, 3
      shows excellent adsorption selectivity for CO2 over N2. 

PMID- 24295279
TI  - Theoretical prediction of XRgCO(+) ions (X = F, Cl, and Rg = Ar, Kr, Xe).
AB  - In this work we have predicted novel rare gas containing cationic molecules,
      XRgCO(+) (X = F, Cl and Rg = Ar, Kr, Xe) using ab initio quantum chemical
      methods. Detail structural, stability, vibrational frequency, and charge
      distribution values are reported using density functional theory, second-order
      Moller-Plesset perturbation theory, and coupled-cluster theory based methods.
      These ions are found to be metastable in nature and exhibit a linear geometry
      with Cinfinityv symmetry in their minima energy structures, and the nonlinear
      transition state geometries are associated with Cs symmetry. Except for the two
      body dissociation channel (Rg + XCO(+)), these ions are stable with respect to
      all other dissociation channels. However, the connecting transition states
      between the above-mentioned two-body dissociation channel products and the
      predicted ions are associated with sufficient energy barriers, which restricts
      the metastable species to transform into the global minimum products. Thus, it
      may be possible to detect and characterize these metastable ions using an
      electron bombardment technique under cryogenic conditions. 

PMID- 24295277
TI  - Early life microbial exposure and fractional exhaled nitric oxide in school-age
      children: a prospective birth cohort study.
AB  - BACKGROUND: Inflammation is a key factor in the pathogenesis of respiratory
      diseases. Early life exposure to microbial agents may have an effect on the
      development of the immune system and on respiratory health later in life.In the
      present work we aimed to evaluate the associations between early life microbial
      exposures, and fractional exhaled nitric oxide (FeNO) at school age. METHODS:
      Endotoxin, extracellular polysaccharides (EPS) and beta(1,3)-D-glucan were
      measured in living room dust collected at 2-3 months of age in homes of
      participants of three prospective European birth cohorts (LISA, n = 182; PIAMA, n
      = 244; and INMA, n = 355). Home dampness and pet ownership were periodically
      reported by the parents through questionnaires. FeNO was measured at age 8 for
      PIAMA and at age 10/11 for LISA and INMA. Cohort-specific associations between
      the indoor microbial exposures and FeNO were evaluated using multivariable
      regression analyses. Estimates were combined using random-effects meta-analyses.
      RESULTS: FeNO at school age was lower in children exposed to endotoxin at age 2-3
      months (beta -0.05, 95% confidence interval (CI) -0.10;-0.01) and in children
      with reported dog ownership during the first two years of life (GM ratio 0.82, CI
      0.70-0.96). FeNO was not significantly associated with early life exposure to
      EPS, beta(1,3)-D-glucan, indoor dampness and cat ownership. CONCLUSION: Early
      life exposure to bacterial endotoxin and early life dog ownership are associated
      with lower FeNO at school age. Further studies are needed to confirm our results
      and to unravel the underlying mechanisms and possible clinical relevance of this
      finding.

PMID- 24295280
TI  - Spin frustration from cis-edge or -corner sharing metal-centered octahedra.
AB  - A new strategy using cis-edge or -corner sharing metal-centered octahedra is
      described which enables interesting frustrated spin lattices to be targeted. The
      examination of "CuV2" triangular motifs in the two new compounds
      [enH2]Cu(H2O)2[V2O2F8] (1) and [Cu(H2O)(2,2'-bpy)]2[V2O2F8] (2) (where enH2 =
      ethylenediammonium and 2,2'-bpy =2,2'-bipyridyl) reveals that the [VOF4](2-)
      anions, which exhibit cis structure directing properties, lead to frustrated
      lattices owing to the competing ferro and antiferromagnetic interactions. There
      is direct coordination through two cis F(-) ligands (i.e., the F(-) ligand trans
      to O(2-) and one equatorial F(-) ligand) in both 1 and 2 owing to the significant
      pi-bonding between the vanadium and the oxide ligand. We emphasize that most of
      triangular motifs reported in the literature are built of cis-edge or -corner
      sharing metal-centered octahedra, thus they can be used to target new materials
      exhibiting interesting magnetism such as spin frustration. 

PMID- 24295281
TI  - Quantitative and stereospecific dihydroxylations of delta(5)-steroids: a green
      synthesis of plant growth hormone intermediates.
AB  - Dihydroxylated Delta(5)-steroids are key intermediates in preparing steroids
      bearing a 5alpha-hydroxy-6-oxo moiety, which are plant growth hormones.
      Quantitative and stereospecific dihydroxylations of Delta(5)-steroids have been
      realized, using H2O2 catalyzed by KI and H2SO4 at 80  degrees C in aqueous
      dioxane. The workup consisted only of concentrating the solvents and filtering
      the products; no chromatography was needed. The reaction conditions tolerate
      various functional groups on the Delta(5)-steroids. A mechanism for this reaction
      is proposed and the reason that the reaction is quantitative and stereospecific
      is explained. 

PMID- 24295282
TI  - A photoswitchable neurotransmitter analogue bound to its receptor.
AB  - Incorporation of the azobenzene derivative gluazo, a synthetic photochromic
      ligand, into a kainate receptor allows for the optical control of neuronal
      activity. The crystal structure of gluazo bound to a dimeric GluK2 ligand-binding
      domain reveals one monomer in a closed conformation, occupied by gluazo, and the
      other in an open conformation, with a bound buffer molecule. The glutamate group
      of gluazo interacts like the natural glutamate ligand, while its trans-azobenzene
      moiety protrudes into a tunnel. This elongated cavity presumably cannot
      accommodate a cis-azobenzene, which explains the reversible activation of the
      receptor upon photoisomerization. 

PMID- 24295283
TI  - Benefits and challenges in practice-oriented psychotherapy research in Germany:
      the TK and the QS-PSY-BAY projects of quality assurance in outpatient
      psychotherapy.
AB  - OBJECTIVE: Two patient-focused long-term research projects performed in the
      German outpatient psychotherapy system are focused on in this article. The TK
      (Techniker Krankenkasse) project is the first study to evaluate a quality
      assurance and feedback system with regard to its practical feasibility in German
      routine care. The other study ("Quality Assurance in Outpatient Psychotherapy in
      Bavaria"; QS-PSY-BAY) was designed to test a new approach for quality assurance
      in outpatient psychotherapy using electronic documentation of patient
      characteristics and outcome parameters. In addition this project provides the
      opportunity to analyze data on health-related costs for the patients undergoing
      outpatient psychotherapy. METHOD: Both projects and their results indicating high
      effect sizes are briefly described. RESULTS: From the perspectives of the
      research teams, advisory boards and other stakeholders, the experiences with
      these projects are discussed focusing on obstacles, challenges, difficulties, and
      benefits in developing and implementing the studies. The triangle collaboration
      of therapists, researchers, and health insurance companies/health service
      institutions turned out to be fruitful in both studies. CONCLUSIONS: Despite some
      controversies between the partners the experiences indicate the importance of
      practiced-research collaborations to provide relevant information about the
      delivery of outpatient psychotherapy in the health system.

PMID- 24295284
TI  - Wild-growing lignicolous mushroom species as sources of novel agents with
      antioxidative and antibacterial potentials.
AB  - Crude extracts of two edible and two medicinal lignicolous mushroom species:
      Meripilus giganteus, Agrocybe aegerita, Fomes fomentarius and Xylaria polymorpha,
      growing wild in Serbia, were analyzed for their antioxidative and antibacterial
      potentials. Free radical scavenging capacity (RSC) on DPPH(*) and (*)OH was
      evaluated both by spectrophotometer and by Electron Spin Resonance (ESR)
      spectroscopy against DPPH(*). The highest antioxidant and antibacterial
      bioactivity was obtained with F. fomentarius extracts (IC50 ~ 10.7 ug/ml in
      DPPH(*) assay; 136.6 mg ascorbic acid equivalents (AAE)/g dry weight (d.w.) for
      ferric reducing antioxidant power FRAP). It also showed the highest total phenol
      (TP) (82.54 mg gallic acid equivalents (GAE)/g dry weight (d.w.)) and total
      flavonoid (TF) content (76.8 ug rutin equivalents (RE)/g dry weight (d.w.)). A.
      aegerita showed the best antioxidant activity (IC50 = 0.87 mg/ml) against DPPH(*)
      in ESR analysis. Total redox potential of extracts was in direct positive
      correlation with TP content (r(2 )= 0.98) and TF content (r(2 )= 0.58). GC/MS
      analysis detected major constituents of extracts, confirming the presence of the
      following organic and phenolic acids: fumaric, succinic, mallic, 4-hydroxy
      benzoic, gentisic, protocatechuic, vanillic, gallic and p-coumaric acid.

PMID- 24295285
TI  - Total synthesis of (+/-)-sculponeatin N.
AB  - The first total synthesis of the (+/-)-sculponeatin N (a 6,7-seco-ent-kaurane
      diterpenoid discovered by Sun and co-workers) has been achieved. The features
      include a regio- and stereoselective aldol reaction to form a lactone, an
      intramolecular Diels-Alder reaction to install B and C rings simultaneously, and
      a radical cyclization to forge the D ring. 

PMID- 24295287
TI  - Rapid and controllable flame reduction of TiO2 nanowires for enhanced solar water
      splitting.
AB  - We report a new flame reduction method to generate controllable amount of oxygen
      vacancies in TiO2 nanowires that leads to nearly three times improvement in the
      photoelectrochemical (PEC) water-splitting performance. The flame reduction
      method has unique advantages of a high temperature (>1000  degrees C), ultrafast
      heating rate, tunable reduction environment, and open-atmosphere operation, so it
      enables rapid formation of oxygen vacancies (less than one minute) without
      damaging the nanowire morphology and crystallinity and is even applicable to
      various metal oxides. Significantly, we show that flame reduction greatly
      improves the saturation photocurrent densities of TiO2 nanowires (2.7 times
      higher), alpha-Fe2O3 nanowires (9.4 times higher), ZnO nanowires (2.0 times
      higher), and BiVO4 thin film (4.3 times higher) in comparison to untreated
      control samples for PEC water-splitting applications. 

PMID- 24295286
TI  - MAR-mediated integration of plasmid vectors for in vivo gene transfer and
      regulation.
AB  - BACKGROUND: The in vivo transfer of naked plasmid DNA into organs such as muscles
      is commonly used to assess the expression of prophylactic or therapeutic genes in
      animal disease models. RESULTS: In this study, we devised vectors allowing a
      tight regulation of transgene expression in mice from such non-viral vectors
      using a doxycycline-controlled network of activator and repressor proteins. Using
      these vectors, we demonstrate proper physiological response as consequence of the
      induced expression of two therapeutically relevant proteins, namely
      erythropoietin and utrophin. Kinetic studies showed that the induction of
      transgene expression was only transient, unless epigenetic regulatory elements
      termed Matrix Attachment Regions, or MAR, were inserted upstream of the regulated
      promoters. Using episomal plasmid rescue and quantitative PCR assays, we observed
      that similar amounts of plasmids remained in muscles after electrotransfer with
      or without MAR elements, but that a significant portion had integrated into the
      muscle fiber chromosomes. Interestingly, the MAR elements were found to promote
      plasmid genomic integration but to oppose silencing effects in vivo, thereby
      mediating long-term expression. CONCLUSIONS: This study thus elucidates some of
      the determinants of transient or sustained expression from the use of non-viral
      regulated vectors in vivo.

PMID- 24295288
TI  - Ionic permeability and mechanical properties of DNA origami nanoplates on solid
      state nanopores.
AB  - While DNA origami is a popular and versatile platform, its structural properties
      are still poorly understood. In this study we use solid-state nanopores to
      investigate the ionic permeability and mechanical properties of DNA origami
      nanoplates. DNA origami nanoplates of various designs are docked onto solid-state
      nanopores where we subsequently measure their ionic conductance. The ionic
      permeability is found to be high for all origami nanoplates. We observe the
      conductance of docked nanoplates, relative to the bare nanopore conductance, to
      increase as a function of pore diameter, as well as to increase upon lowering the
      ionic strength. The honeycomb lattice nanoplate is found to have slightly better
      overall performance over other plate designs. After docking, we often observe
      spontaneous discrete jumps in the current, a process which can be attributed to
      mechanical buckling. All nanoplates show a nonlinear current-voltage dependence
      with a lower conductance at higher applied voltages, which we attribute to a
      physical bending deformation of the nanoplates under the applied force. At
      sufficiently high voltage (force), the nanoplates are strongly deformed and can
      be pulled through the nanopore. These data show that DNA origami nanoplates are
      typically very permeable to ions and exhibit a number of unexpected mechanical
      properties, which are interesting in their own right, but also need to be
      considered in the future design of DNA origami nanostructures. 

PMID- 24295289
TI  - Determining optimal noninvasive parameters for the prediction of left ventricular
      remodeling in chronic ischemic patients.
AB  - OBJECTIVES: DOPPLER-CIP aims to determine the optimal noninvasive parameters
      (myocardial function, perfusion, ventricular blood flow, cell integrity) and
      methodology (ergometry, echocardiography, scintigraphy, MRI) in a given ischemic
      substrate that best predicts the impact of an intervention (or the lack thereof)
      on adverse morphological ventricular remodeling and functional recovery.
      Moreover, the relative predictive value of each of these parameters, in respect
      to the cost of extracting this information in order to enable optimization of
      cost-effectiveness for improved health care, will be determined by this project.
      DESIGN: DOPPLER-CIP is a multi-center registry study. All patients with ischemic
      heart disease included in this study undergo at least two noninvasive stress
      imaging examinations at baseline. The presence/or absence of left ventricular
      (LV) remodeling will be assessed after a follow-up of 2 years, during which all
      cardiac events will be registered. RESULTS: 676 patients were included.
      Currently, baseline data analysis is almost finished and the follow-up is
      ongoing. CONCLUSIONS: After completion, DOPPLER-CIP will provide evidence-based
      guidelines toward the most effective use of cardiac imaging in the chronically
      ischemic heart disease patient. The study will generate information, knowledge,
      and insight into the new imaging methodologies and into the pathophysiology of
      chronic ischemic heart disease.

PMID- 24295290
TI  - Point-of-care ultrasonography changes patient management following open heart
      surgery.
AB  - OBJECTIVES: Although pericardial effusions (PE) and pleural effusions (PLE) may
      lead to life-threatening respiratory and circulatory deterioration following open
      heart surgery the postoperative frequency is not fully recognized. The diagnosis
      is typically based on ultrasonography, X-ray or computer tomography and often
      disclosed when circulatory collapse is evident. Point-of-care (POC)
      ultrasonography protocols constitute a noninvasive evaluation of the
      cardiopulmonary status. We hypothesized that POC ultrasonography could diagnose
      unknown PE and PLE. DESIGN: Patients scheduled for open heart surgery were
      eligible for inclusion. Baseline evaluation including POC examination and dyspnea
      score was performed one day prior to surgery and repeated on the 4th and 30th
      postoperative day. RESULTS: Eighty patients were included and complete follow-up
      was 80%. Thirteen patients (19%) had PE on the 4th day postsurgery and 19
      patients (30%) had PE on the 30th day. Ultrasonography facilitated change in
      management in one patient with PE requiring drainage. Forty-nine patients (70%)
      had PLE on the 4th day following surgery and 19 patients (30%) had PLE on the
      30th postoperative day. Ultrasonography facilitated a change in management in
      seven patients with PLE requiring drainage. CONCLUSION: POC ultrasonography
      detected pathology, otherwise undisclosed, and was responsible for a change in
      management in a considerable number of cases.

PMID- 24295291
TI  - Predictors for not completing exercise-based rehabilitation following cardiac
      surgery.
AB  - OBJECTIVES: The beneficial effects of exercise-based cardiac rehabilitation (ECR)
      are well documented. A substantial proportion of patients fail to complete ECR.
      The purpose of this study was to identify factors associated with patients not
      completing ECR. DESIGN: Registry based and data from medical records. The study
      population was surgically treated heart patients with ischaemic and/or heart
      valve diseases referred to ECR between August 2008 and January 2011 at Aarhus
      University Hospital, Denmark. The ECR was an 8-week course with 1-h biweekly
      sessions. Patients were non-completers when attending <= 75% of sessions. Data
      were analysed in a multivariate logistic regression model. RESULTS: Of 364
      patients, 73% were referred to ECR, 42% did not complete the ECR and 28% never
      showed up. Readmission within 8 weeks post-discharged odds ratio (OR) of 2.50
      (95% confidence interval [CI], 1.40-4.46), prescribed antidepressant medication
      OR of 2.40 (95% CI, 1.21-4.74), overweight OR of 1.81 (95% CI, 1.03-3.18), or
      being single OR of 1.12 (95% CI, 1.07-1.70) was significantly associated with not
      completing ECR. CONCLUSION: We identified a high rate of patients not completing
      ECR. Readmissions, antidepressant medication, marital status and obesity should
      warrant clinical attention when designing future interventions to improve
      adherence to ECR.

PMID- 24295292
TI  - Degradation of neutrophil extracellular traps is decreased in patients with
      antiphospholipid syndrome.
AB  - OBJECTIVES: A decreased ability to degrade neutrophil extracellular traps (NETs)
      is seen in a subgroup of patients with systemic lupus erythematosus (SLE) and
      correlates with the presence of autoantibodies. Antiphospholipid syndrome (APS)
      can develop secondary to SLE or as a primary disease. In the current study we
      investigated the ability of sera from patients with APS to degrade NETs. The
      presence of antibodies against NETs and neutrophil remnants were also determined
      in the same patients. METHODS: In the study, 106 patients with APS (73 primary
      and 33 secondary), 76 patients with systemic sclerosis (SSc) and 77 healthy
      donors as control samples were included. NETs generated from neutrophils isolated
      from healthy volunteers were incubated with patient sera, followed by measurement
      of degraded NETs or deposited IgG. RESULTS: Sera of APS patients had a decreased
      ability to degrade NETs compared to healthy controls, with no difference between
      primary and secondary APS. Sera from SSc patients did not differ significantly
      from healthy controls in the ability to degrade NETs. A decreased degradation of
      NETs correlated weakly to increased levels of antibodies against NETs/neutrophil
      remnants in patients with primary APS, but stronger in patients with secondary
      APS. CONCLUSIONS: The ability to degrade NETs is decreased in a subgroup of
      patients with APS and is associated with antibodies against NETs and specific
      clinical manifestations in those patients.

PMID- 24295293
TI  - Intraoperative electron radiation therapy (IOERT) in patients with locally
      recurrent renal cell carcinoma.
AB  - BACKGROUND: To analyze our experience with intraoperative electron radiation
      therapy (IOERT) followed by moderate doses of external beam radiation therapy
      (EBRT) in patients with locally recurrent renal cell carcinoma. METHODS: From
      1992 to 2010, 17 patients with histologically proven, locally recurrent renal
      cell carcinoma (median tumor size 7 cm) were treated by surgery and IOERT with a
      median dose of 15 Gy. All patients met the premise of curative intent including 7
      patients with oligometastases at the time of recurrent surgery, which were
      resected and/or irradiated. The median time interval from primary surgery to
      local recurrence was 26 months. Eleven patients received additional 3D-conformal
      EBRT with a median dose of 40 Gy. RESULTS: Surgery resulted in free but close
      margins in 6 patients (R0), while 9 patients suffered from microscopic (R1) and 2
      patients from macroscopic (R2) residual disease. After a median follow-up of 18
      months, two local recurrences were observed, resulting in an actuarial 2-year
      local control rate of 91%. Eight patients developed distant failures,
      predominantly to liver and bone, resulting in an actuarial 2-year progression
      free survival of 32%. An improved PFS rate was found in patients with a larger
      time interval between initial surgery and recurrence (> 26 months). The actuarial
      2-year overall survival rate was 73%. Lower histological grading (G1/2) was the
      only factor associated with improved overall survival. Perioperative
      complications were found in 4 patients. No IOERT specific late toxicities were
      observed. CONCLUSIONS: Combination of surgery, IOERT and EBRT resulted in high
      local control rates with low toxicity in patients with locally recurrent renal
      cell cancer despite an unfavorable surgical outcome in the majority of patients.
      However, progression-free and overall survival were still limited due to a high
      distant failure rate, indicating the need for intensified systemic treatment
      especially in patients with high tumor grading and short interval to recurrence.

PMID- 24295295
TI  - Who uses Australian chiropractic services?
AB  - BACKGROUND: The use of chiropractic services is widespread, however, little is
      known about the characteristics of people who seek chiropractic care in
      Australia. This study compared the characteristics of users and non-users of
      chiropractic services from a cohort of patients sourced from general medical
      practice in Victoria, Australia. METHODS: This is a secondary analysis of
      baseline screening data from a prospective adult cohort study beginning in 2005.
      Thirty randomly selected Australian general medical practices mailed out surveys
      to 17,780 of their patients. Differences were examined between chiropractic users
      and others, and between chiropractic users who reported a back problem to those
      who did not. RESULTS: Of 7,519 respondents, 15% indicated they had visited a
      chiropractor in the last 12 months. Chiropractic users were more likely to have
      their GP located in a rural location and to be born in Australia; they were less
      likely to be in the older age group (55-76), to be unemployed or to have a
      pension/benefit as their main source of income. Chiropractic users were more
      likely to: have a back problem; use complementary or alternative medication;
      visit another type of complementary health practitioner or a physiotherapist.
      They were less likely to take medication for certain health problems (e.g. for
      high blood pressure, high cholesterol or asthma). No important differences were
      seen between chiropractic users and non-users for other health problems. People
      who visited a chiropractor and reported a back problem were more likely to: be a
      current smoker; have a number of other chronic conditions, including arthritis,
      hypertension, chronic sinusitis, asthma, dermatitis, depression and anxiety;
      report taking medications, including antidepressants, analgesics (painkillers and
      arthritis medication) and complementary or alternative medications. CONCLUSIONS:
      This large cross-sectional study of general medical practice attendees suggests
      that chiropractors are the most commonly consulted complementary health
      profession. Chiropractors should ensure they are aware of their patients' health
      conditions other than musculoskeletal problems and should ensure they are
      appropriately managed.

PMID- 24295294
TI  - Glutaredoxin 2 reduces both thioredoxin 2 and thioredoxin 1 and protects cells
      from apoptosis induced by auranofin and 4-hydroxynonenal.
AB  - AIMS: Mitochondrial thioredoxin (Trx) is critical for defense against oxidative
      stress-induced cell apoptosis. To date, mitochondrial thioredoxin reductase
      (TrxR) is the only known enzyme catalyzing Trx2 reduction in mitochondria.
      However, TrxR is sensitive to inactivation by exo/endogenous electrophiles, for
      example, 4-hydroxynonenal (HNE). In this study, we characterized the
      mitochondrial glutaredoxin 2 (Grx2) system as a backup for the mitochondrial
      TrxR. Meanwhile, as Grx2 is also present in the cytosol/nucleus of certain cancer
      cell lines, the reducing activity of Grx2 on Trx1 was also tested. RESULTS:
      Glutathione alone could reduce oxidized Trx2, and the presence of physiological
      concentrations of Grx2 markedly increased the reaction rate. HeLa cells with Grx2
      overexpression (particularly in the mitochondria) exhibited higher viabilities
      than the wild-type cells after treatment with TrxR inhibitors (Auranofin or HNE),
      whereas knockdown of Grx2 sensitized the cells to TrxR inhibitors. Accordingly,
      Grx2 overexpression in the mitochondria had protected Trx2 from oxidation by HNE
      treatment, whereas Grx2 knockdown had sensitized Trx2 to oxidation. On the other
      hand, Grx2 reduced Trx1 with similar activities as that of Trx2. Overexpression
      of Grx2 in the cytosol had protected Trx1 from oxidation, indicating a supportive
      role of Grx2 in the cytosolic redox balance of cancer cells. INNOVATION: This
      work explores the reductase activity of Grx2 on Trx2/1, and demonstrates the
      physiological importance of the activity by using in vivo redox western blot
      assays. CONCLUSION: Grx2 system could help to keep Trx2/1 reduced during an
      oxidative stress, thereby contributing to the anti-apoptotic signaling.

PMID- 24295296
TI  - N-succinyl chitosan as buccal penetration enhancer for delivery of herbal agents
      in treatment of oral mucositis.
AB  - Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%)
      and radiotherapy (over 50%). Current palliative treatments of oral mucositis
      include specialized agents like pelifermin, platelet derived factors etc. or oral
      hygienic agents which suffered from various drawbacks like systemic side effect,
      least effect owing to fast wash out of buccal mucosa, patient unfriendly delivery
      systems, and mere symptomatic relief. In this research work, N-succinyl chitosan
      gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was
      prepared to explore their multiple and synergistic effects on various
      pathological factors of oral mucositis. N-succinyl chitosan was synthesized in
      our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v)
      and sodium hyaluronate (0.2% w/v) to prepare orogel with optimum pH,
      spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release
      from N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be
      87.45+/-0.14%, which was better in comparison to that released from chitosan gel.
      Ex vivo penetration studies using rat buccal mucosal tissue also suggested better
      J-efflux of eugenol through N-succinyl chitosan in comparison to chitosan gel
      with enhancement ratio (ER) of 1.71. The antimicrobial effect of N-succinyl
      chitosan based orogel against S. aureus and C. albicans efficacy was found to be
      statistically high in comparison to chitosan based orogel as well as marketed
      formulation of chlorhexidine (p<0.05). The N-succinyl chitosan orogel in 5-fluoro
      uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival
      ratio, weight gain and high tissue regeneration activity than chitosan gel
      formulation within 15 days. The formulation was successful in elevating the
      survival and reducing the inflammation in the oral mucosa of animals compared to
      disease control (p<0.05) and hence suggesting the potential of N-succinyl
      chitosan orogel in the treatment of oral mucositis. 

PMID- 24295297
TI  - Analysis of Golgi complex functions: in vitro reconstitution systems.
AB  - In vitro reconstitution is prerequisite to investigate complex cellular functions
      at the molecular level. Reconstitution systems range from combining complete
      cellular cytosol with organelle-enriched membrane fractions to liposomal systems
      where all components are chemically defined and can be chosen at will. Here, we
      describe the in vitro reconstitution of COPI-coated vesicles from semi-intact
      cells. Efficient vesicle formation is achieved by simple incubation of
      permeabilized cells with the minimal set of coat proteins Arf1 and coatomer, and
      guanosine trinucleotides. GTP hydrolysis or any mechanical manipulations are not
      required for efficient COPI vesicle release. 

PMID- 24295298
TI  - RNA interference approaches to examine Golgi function in animal cell culture.
AB  - The ability to deplete specific proteins from cells has transformed cell biology.
      Targeting of gene transcripts using RNA interference has allowed for a highly
      refined approach to the analysis of gene function that has been applied to all
      aspects of cell biology. Developments of the technology have reached a point
      where it is now a relatively trivial task to assess the role of an individual
      protein in a particular cell function. RNAi also allows for genome-wide screening
      as a discovery step toward the identification of new components of cellular
      pathways and machines. The technique has been applied extensively to the analysis
      of Golgi complex function, leading to significant insight into the biology of
      this complex organelle. Here, we describe the commonly used options for targeting
      individual genes for both transient and stable knockdown. We consider the
      alternative methods for introducing these reagents into cells and outline methods
      that we and others have used widely for validation of specificity and efficacy of
      gene targeting. 

PMID- 24295299
TI  - Trafficking along the secretory pathway in Drosophila cell line and tissues: a
      light and electron microscopy approach.
AB  - In the past, Drosophila has been used for molecular and developmental biology
      studies that have led to many important conceptual advances. In the last decade,
      this model organism has also been utilized to address cell biology issues, in
      particular those related to membrane traffic through the secretory pathway. This
      has confirmed that the functional organization of the secretory pathway is
      conserved and it allowed further integrating secretion to signaling and
      development. Furthermore, Drosophila tissue culture S2 cells have been the basis
      of many RNAi screens, some addressing aspects of the functional organization of
      the secretory pathway and others identifying proteins of the secretory pathway in
      seemingly unrelated processes. Taken together, studying the protein trafficking
      and the organization of the secretory pathway both in S2 cells and in tissues has
      become important. Here, we review light and electron microscopy techniques
      applied to Drosophila that allow gaining insight into the secretory pathway, and
      can easily be extended to other cell biology-related fields. 

PMID- 24295300
TI  - Studying membrane trafficking in the worm C. elegans by RNA interference.
AB  - A powerful approach to gain understanding of molecular machinery responsible for
      membrane trafficking is through inactivation of gene function by RNA interference
      (RNAi). RNAi-mediated gene silencing occurs when a double-stranded RNA is
      introduced into cells and targets a complementary mRNA for degradation. The
      subsequent lack of mRNA prevents the synthesis of the corresponding protein and
      ultimately causes depletion of a particular gene product from the cell. The
      effects of such depletion can then by analyzed by functional, morphological, and
      biochemical assays. RNAi-mediated knockdowns of numerous gene products in
      cultured cells of mammalian and other species origins have provided significant
      new insight into traffic regulation and represent standard approaches in current
      cell biology. However, RNAi in the multicellular nematode Caenorhabditis elegans
      model allows RNAi studies within the context of a whole organism, and thus
      provides an unprecedented opportunity to explore effects of specific trafficking
      regulators within the context of distinct developmental stages and diverse cell
      types. In addition, various transgenic C. elegans strains have been developed
      that express marker proteins tagged with fluorescent proteins to facilitate the
      analysis of trafficking within the secretory and endocytic pathways. This chapter
      provides a detailed description of a basic RNAi approach that can be used to
      analyze the function of any gene of interest in secretory and endosomal
      trafficking in C. elegans. 

PMID- 24295301
TI  - Endomembrane and Golgi traffic in plant cells.
AB  - Leaf epidermal cells make ideal specimens for the investigation of the plant
      secretory pathway in that it is relatively easy to tag with fluorescent proteins
      and visualize in vivo the various organelles of the pathway. A number of
      techniques can be employed to identify and study proteins within the endomembrane
      organelles and to study their dynamics and interactions. Here, we discuss the
      most commonly used approaches to express proteins within arabidopsis and tobacco
      leaves, the use of mutant screens to identify trafficking proteins, and the use
      of two in vivo techniques, Fluorescence recovery after photobleaching and Forster
      resonance energy transfer, to study protein dynamics in plant cells. 

PMID- 24295302
TI  - Biochemical analysis of secretory trafficking in mammalian cells.
AB  - Protein trafficking within the secretory pathway of mammalian cells is amenable
      to analysis by biochemical methods. This can be achieved by monitoring
      posttranslational modifications that occur naturally within the secretory
      pathway, or by measuring the delivery of cargo to the cell surface or
      extracellular medium. These approaches can be combined with additional
      manipulations such as specific temperature blocks that permit analysis of
      distinct trafficking steps. Biochemical analysis is advantageous in that it
      permits both a sensitive and quantitative measure of trafficking along the
      pathway. The methods discussed in this chapter permit the analysis of trafficking
      of both endogenous cargo proteins and ectopically expressed model cargos, which
      can be followed using either Western blotting or metabolic pulse-chase
      approaches. These methods are relatively straightforward and suitable for use in
      most modern cell biology laboratories. In addition to the well-established
      methods that we describe here in detail, we also refer to the development of more
      recent tailored approaches that add further to the arsenal of tools that can be
      used to assess trafficking in the secretory pathway. 

PMID- 24295303
TI  - Methods for analysis of apical lumen trafficking using micropatterned 3D systems.
AB  - Epithelial organs are made of interconnected branched networks of tubules, with a
      central lumen lined by a monolayer of epithelial cells. Certain epithelial cell
      lines can be converted into organotypic cultures by the addition of extracellular
      matrix components. When cultured in these conditions, epithelial cells reorient
      the axis of polarity, reorganize the membrane surfaces, and transport apical
      proteins to form the lumen in a process that recapitulates essential aspects of
      de novo apical membrane formation during epithelial organ morphogenesis.
      Micropatterns are a simple technique that allows cell culture in a controlled
      adhesive environment with extremely high precision, close to the nanometer scale.
      We have recently developed a method to culture MDCK cysts on micropatterns of
      different sizes and composition. Using this method we found that changes in
      micropattern shape and size can be used to modify cell contractility to
      understand its contribution to apical membrane formation. When imaging cysts on
      micropatterns the main advantage is that apical-directed vesicle trafficking is
      visualized in the x-y plane, which presents higher resolution on confocal
      microscopes. Thus, the use of micropatterns is an efficient setup to analyze
      polarized secretion with unprecedented higher resolution in both time and space. 

PMID- 24295304
TI  - Using replication defective viruses to analyze membrane trafficking in polarized
      epithelial cells.
AB  - Epithelial cells in culture, especially once they are polarized, are extremely
      hard to manipulate by transient transfection methods. The use of replication
      defective adenoviruses for gene expression or replication defective retroviruses
      or lentiviruses to express shRNA for gene knockdown provides efficient tools to
      manipulate gene expression patterns even in hard-to-transfect cell lines. One of
      the advantages of using defective adenoviruses for gene expression is that once
      the virus has been generated, it can easily be applied to a wide variety of
      cells. In addition, replication defective retro- and lentiviruses are used to
      stably deplete proteins from cell lines, which subsequently may be used for
      analyzing the polarized surface delivery of receptors that may be expressed using
      defective adenoviruses. The latter approach is especially useful if the expressed
      shRNA also encodes GFP for easy assessment of shRNA-expressing cells. Thus the
      use of defective viruses in epithelial cell research is convenient. This makes a
      detailed infection protocol a research tool that would be valuable to many
      laboratories. Here we describe in detail how cells are infected with defective
      retro- or lentiviruses and subsequently selected for stable gene knockdown. We
      then describe how these cells may be used for infection with defective
      adenoviruses and the subsequent analyses. 

PMID- 24295305
TI  - SNAP-tagging the retrograde route.
AB  - We have developed a chemical biology strategy to identify proteins that follow
      the retrograde transport route from the plasma membrane to the Golgi apparatus,
      via endosomes. The general principle is the following: plasma membrane proteins
      are covalently tagged with a first probe. Only the ones that are then transported
      to trans-Golgi/TGN membranes are covalently bound to a capture reagent that has
      been engineered into this compartment. Specifically, the first probe is
      benzylguanine (BG) that is conjugated onto primary amino groups of plasma
      membrane proteins. The capture reagent includes an O(6)-alkylguanine-DNA
      alkyltransferase-derived fragment, the SNAP-tag, which forms a covalent linkage
      with BG. The SNAP-tag is fused to the GFP-tagged Golgi membrane anchor from
      galactosyl transferase for proper targeting to trans-Golgi/TGN membranes. Cell
      surface BG-tagged proteins that are transported to trans-Golgi/TGN membranes
      (i.e., that are retrograde cargoes) are thereby covalently captured by the SNAP
      tag fusion protein. For identification, the latter is immunopurified using GFP
      Trap, and associated retrograde cargo proteins are identified by mass
      spectrometry. We here provide a step-by-step protocol of this method. 

PMID- 24295306
TI  - Assessing ER and Golgi N-glycosylation process using metabolic labeling in
      mammalian cultured cells.
AB  - Modifications of N-glycosylation in disease states are common and illustrate the
      crucial requirement of glycosylation in human biology. Mainly based on glycan
      permethylation and the use of mass spectrometry analysis, we can easily
      understand that many different methods to analyze the N-glycome have seen the
      day. While extremely powerful, these methods are mainly used to analyze
      qualitative variations of N-glycosylation of human serum proteins and do not
      necessarily reflect the glycosylation status of derived mammalian cultured cells.
      This chapter summarizes two methods that we are routinely using in our laboratory
      to assess the ER and Golgi N-glycosylation process. The proposed methodology
      allows pinpointing ER as well as Golgi glycosylation deficiencies in mammalian
      cultured cells. The first approach is based on direct metabolic labeling of
      cultured mammalian cells with [2-(3)H] mannose followed by sequential extraction
      and HPLC analysis of the purified oligosaccharides. The second one is based on
      the copper-catalyzed azide alkyne cycloaddition (CuAAC) strategy. We propose the
      use of alkyne-tagged sialic acid (SialNAl) to visualize the Golgi glycosylation
      efficiency. Their metabolic incorporation into newly synthesized glycoproteins
      can then be chemoselectively coupled to complementary azide-functionalized
      fluorophores, and visualized by using confocal laser scanning microscopy. To
      summarize, we present here a detailed description of our know-how in the field of
      ER and Golgi N-glycosylation. 

PMID- 24295307
TI  - Fluorescence-based analysis of trafficking in mammalian cells.
AB  - Proteins destined for the secretory pathway start their journey in the
      endoplasmic reticulum and transit through the Golgi complex to be delivered to
      their destination compartment. Over the last decades, several fluorescence-based
      assays were developed to analyze the transport of proteins along the secretory
      pathway. In this review, we briefly introduce the existing tools. We provide
      detailed protocols to allow the reader to use the newly developed secretory assay
      termed the RUSH system (Retention Using Selective Hooks). This assay enables the
      synchronous release of one to three cargos of interest from a donor compartment
      (the endoplasmic reticulum). Analysis of the transport steps of the cargos from
      the donor compartment to the acceptor compartment is accomplished by fluorescence
      based methods. 

PMID- 24295308
TI  - Photobleaching methods to study Golgi complex dynamics in living cells.
AB  - The Golgi complex (GC) is a highly dynamic organelle that constantly receives and
      exports proteins and lipids from both the endoplasmic reticulum and the plasma
      membrane. While protein trafficking can be monitored with traditional biochemical
      methods, these approaches average the behaviors of millions of cells, provide
      modest temporal information and no spatial information. Photobleaching methods
      enable investigators to monitor protein trafficking in single cells or even
      single GC stacks with subsecond precision. Furthermore, photobleaching can be
      exploited to monitor the behaviors of resident GC proteins to provide insight
      into mechanisms of retention and trafficking. In this chapter, general
      photobleaching approaches with laser scanning confocal microscopes are described.
      Importantly, the problems associated with many fluorescent proteins (FPs) and
      their uses in the secretory pathway are discussed and appropriate choices are
      suggested. For example, Enhanced Green Fluorescent Protein (EGFP) and most red
      FPs are extremely problematic. Finally, options for data analyses are described. 

PMID- 24295309
TI  - Photohighlighting approaches to access membrane dynamics of the Golgi apparatus.
AB  - By providing quantitative, visual data of live cells, fluorescent protein-based
      microscopy techniques are furnishing novel insights into the complexities of
      membrane trafficking pathways and organelle dynamics. In this chapter, we
      describe experimental protocols employing fluorescent protein-based
      photohighlighting techniques to quantify protein movement into and out of the
      Golgi apparatus, an organelle that serves as the central sorting and processing
      station of the secretory pathway. The methods allow kinetic characteristics of
      Golgi-associated protein trafficking to be deciphered, which can help clarify how
      the Golgi maintains itself as a steady-state structure despite a continuous flux
      of secretory cargo passing into and out of this organelle. The guidelines
      presented in this chapter can also be applied to examine the dynamics of other
      intracellular organelle systems, elucidating mechanisms for how proteins are
      maintained in specific organelles and/or circulated to other destinations within
      the cell. 

PMID- 24295310
TI  - Live cell visualization of Golgi membrane dynamics by super-resolution confocal
      live imaging microscopy.
AB  - Super-resolution confocal live imaging microscopy we developed provides cutting
      edge high-speed live cell imaging at high space resolution. With this technology
      we are now able to observe details of membrane traffic events, including
      behaviors of small vesicles, cisternal maturation of the Golgi apparatus, and
      membrane segregation within a compartment. 

PMID- 24295311
TI  - Analysis of Golgi complex function using correlative light-electron microscopy.
AB  - Though it has been studied for more than 100 years, the Golgi complex remains a
      fascinating organelle for cell biologists. This is because it is a unique
      intracellular structure with a list of well-known functions that continues to
      grow with the discovery of new genes and the development of novel advanced
      techniques. The Golgi apparatus has been carefully characterized in different
      organisms, tissues, and cell types both by light and by electron microscopy.
      However, the new quality step in Golgi research began with the development of
      correlative light-electron microscopy (CLEM). This innovative method allows
      visualizing the fate of the same organelle of interest at any moment of its life
      span first by video imaging in live cells and then by immunoelectron microscopy
      and 3D reconstruction. Here, we will present the historical overview of different
      Golgi-associated processes characterized by CLEM and describe the detailed
      protocol of this complex yet valuable technique. 

PMID- 24295312
TI  - Viewing Golgi structure and function from a different perspective--insights from
      electron tomography.
AB  - Historically, ultrastructural investigations, which have focused on elucidating
      the biological idiosyncrasies of the Golgi apparatus, have tended towards
      oversimplified or fallacious hypotheses when postulating how the Golgi apparatus
      reorganizes itself both structurally and functionally to fulfill the plethora of
      cellular processes underpinned by this complex organelle. Key questions are still
      unanswered with regard to how changes in Golgi architecture correlate so
      reproducibly to changes in its functional priorities under different
      physiological conditions or experimental perturbations. This fact alone serves to
      highlight how the technical limitations associated with conventional two
      dimensional imaging approaches employed in the past failed to adequately capture
      the extraordinary complexity of the Golgi's three-dimensional (3D) structure-now
      a hallmark of this challenging organelle. Consequently, this has hampered
      progress towards developing a clear understanding of how changes in its structure
      and function typically occur in parallel. In this chapter, we highlight but a few
      of the significant new insights regarding variations in the Golgi's structure
      function relationships that have been afforded over recent years through advanced
      electron microscopic techniques for 3D image reconstruction, commonly referred to
      as electron tomography. 

PMID- 24295313
TI  - High-content screening and analysis of the Golgi complex.
AB  - High-content screening (HCS) as a methodological tool has evolved relatively
      recently, largely driven by the demand for in depth spatial and temporal
      information from intact cells exposed to a range of chemical and/or genomic
      perturbations. The technology is based around automated fluorescence microscopy
      in combination with advanced imaging processing and analysis tools, which
      together can provide quantitative information as a first-level description of
      complex cellular events. HCS and high-content analysis are particularly powerful
      when combined with perturbation techniques such as RNA interference (RNAi), as
      this allows large families of genes to be interrogated with respect to a
      biological pathway or process of interest. In this methodology chapter, we
      describe an approach by which HCS can be applied to study the morphological state
      of the Golgi complex in cultured mammalian cells. We provide a detailed protocol
      for the highly parallel downregulation of gene activity using RNAi in 384-well
      plates and describe an automated image analysis routine that could be used to
      quantify Golgi complex in a genome-wide RNAi context. 

PMID- 24295314
TI  - (Re)modeling the Golgi.
AB  - In this chapter, we summarize recent theoretical efforts to address a variety of
      issues in Golgi morphogenesis: de novo biogenesis of compartments with precise
      chemical identity, the transport of proteins through the Golgi, the maintenance
      of chemical identity, and the morphology of Golgi compartments, from the
      perspective of nonequilibrium physics. 

PMID- 24295315
TI  - Golgi depletion from living cells with laser nanosurgery.
AB  - How Golgi biogenesis occurs in mammalian cells is a controversial problem. Can
      the Golgi complex (GC) form de novo from ER membranes or does it require a
      template? The method described in this chapter uses growth of cells on
      micropatterns to displace the GC from its juxtanuclear position and laser
      nanosurgery to subsequently deplete it from living cells. Golgi-depleted
      karyoplasts can be followed by time-lapse microscopy to address if and how the GC
      can be de novo synthesized from ER membranes. Furthermore, the study of different
      processes in the absence of the GC can shed light on the role of this organelle
      in the intracellular signaling and homeostasis. 

PMID- 24295316
TI  - Studying intracellular trafficking pathways with probabilistic density maps.
AB  - The compartmentalization of cellular functions in complex membranous organelles
      is a key feature of eukaryotic cells. To cope with the enormous complexity of
      trafficking pathways that connect these compartments, new approaches need to be
      considered and introduced into the field of cell biology. We exploit the
      advantages of the "micropatterning technique," which is to bring cells to adopt a
      highly reproducible shape, and probabilistic density mapping, which quantifies
      spatial organization of trafficking compartments, to study regulatory mechanisms
      of intracellular trafficking. Here, we provide a protocol to analyze and quantify
      alterations in trafficking compartments upon cellular manipulation. We
      demonstrate how this approach can be employed to study the regulation of Rab6
      labeled transport carriers by the cytoskeleton. 

PMID- 24295317
TI  - Methods to study signaling at the Golgi apparatus.
AB  - Research on the secretory pathway in the past three decades accounts for our
      known knowledge about the composition and architecture of organelles and about
      the machinery that regulates membrane transport. An emerging topic in the past
      few years was the discovery that the secretory pathway is regulated by signaling,
      and in this regard, the Golgi apparatus received major attention. In the current
      chapter, we will highlight various techniques that are used by us and others to
      study signaling at the Golgi. We describe methods to study lipid and protein
      phosphorylation at the Golgi and various techniques for studying spatial
      activation of GTPases at this organelle. We also discuss how combining these
      techniques and improving their limitations is important for gaining a better
      understanding of how the Golgi intersects with various signal transduction
      pathways. 

PMID- 24295318
TI  - Golgi-dependent signaling: self-coordination of membrane trafficking.
AB  - Multiple studies have shown that endomembranes can act as signaling platforms for
      plasma-membrane-originated signaling. In particular, the Golgi complex operates
      as a relay station for signaling, which is initiated by classical ligand-receptor
      systems at the plasma membrane, acting as a positive or negative regulator of
      these plasma-membrane signals. Thus, the Golgi complex has emerged as a hub for
      intracellular signaling. Furthermore, recent evidence has indicated that the
      Golgi complex can also trigger its own signaling cascades, which involve some of
      the molecular players that are classically engaged in signal transduction at the
      plasma membrane. This aspect of the Golgi complex, namely, the ability to
      generate autonomous signaling, has been experimentally addressed only in the last
      few years. These studies have revealed that the transport vesicles that leave the
      ER for the Golgi complex also carry signal molecules that can then be sensed by a
      receptor in the Golgi complex to coordinate secretory organelles. The receptor
      involved in the sensing of incoming traffic at the Golgi complex has been shown
      to be the KDEL receptor (KDELR), a proposed new G-protein-coupled receptor. Upon
      binding to a KDEL-containing ligand (a chaperone), the KDELR can activate a
      signaling cascade that regulates anterograde intra-Golgi trafficking. However,
      this Golgi-based signaling response is only partially understood to date. Here we
      report on several approaches that are suitable for the study of traffic-initiated
      and KDELR-dependent signaling. 

PMID- 24295321
TI  - Methods in Cell Biology. Methods for analysis of Golgi complex function. Preface.

PMID- 24295320
TI  - Ice recovery assay for detection of Golgi-derived microtubules.
AB  - Proper organization of the microtubule cytoskeleton is essential for many
      cellular processes including maintenance of Golgi organization and cell polarity.
      Traditionally, the centrosome is considered to be the major microtubule
      organizing center (MTOC) of the cell; however, microtubule nucleation can also
      occur through centrosome-independent mechanisms. Recently, the Golgi has been
      described as an additional, centrosome-independent, MTOC with distinct cellular
      functions. Golgi-derived microtubules contribute to the formation of an
      asymmetric microtubule network, control Golgi organization, and support polarized
      trafficking and directed migration in motile cells. In this chapter, we present
      an assay using recovery from ice treatment to evaluate the potential of the
      Golgi, or other MTOCs, to nucleate microtubules. This technique allows for clear
      separation of distinct MTOCs and observation of newly nucleated microtubules at
      these locations, which are normally obscured by the dense microtubule network
      present at steady-state conditions. This type of analysis is important for
      discovery and characterization of noncentrosomal MTOCs and, ultimately,
      understanding of their unique cellular functions. 

PMID- 24295319
TI  - Signaling at the Golgi during mitosis.
AB  - The Golgi complex of mammalian cells is composed of interconnected stacks of
      flattened cisternae that form a continuous membrane system in the pericentriolar
      region of the cell. At the onset of mitosis, this so-called Golgi ribbon is
      converted into small tubular-vesicular clusters in a tightly regulated
      fragmentation process, which leads to a temporary loss of the physical Golgi
      centrosome proximity. Mitotic Golgi breakdown is required for Golgi partitioning
      into the two daughter cells, cell cycle progression and may contribute to the
      dispersal of Golgi-associated signaling molecules. Here, we review our current
      understanding of the mechanisms that control mitotic Golgi reorganization, its
      biological significance, and assays that are used to study this process. 

PMID- 24295322
TI  - Improved mechanical stability of acetoxypropyl cellulose upon blending with
      ultranarrow PbS nanowires in Langmuir monolayer matrix.
AB  - Cellulose and cellulose derivatives have long been used as membrane fabrication.
      Langmuir monolayer behavior, which naturally mimics membranes, of acetoxypropyl
      cellulose (APC) and lead sulfide (PbS) nanowire mixtures at different volume
      ratios is reported. Surface pressure (pi)-area (A) isotherms of APC and PbS
      nanowires mixtures at different volume ratios show a gradual decrease in the
      monolayer area with increasing volume fraction of PbS nanowires. Change of
      surface potential with monolayer area at different volume ratios also reveals a
      gradual increase in the surface potential indicating incorporation of PbS
      nanowires within APC matrix. The compressibility and elastic constants
      measurements reveal an enhancement of the elasticity upon incorporation of PbS
      nanowires up to certain volume fractions. An enhancement in stability of the
      blend is observed upon PbS nanowire incorporation to the APC matrix. Rheological
      measurements also support the robustness of the mixture of APC and PbS nanowires
      in 3D bulk phase. Such robust ultrathin films of cellulose based-nanowire blend
      obtained by means of the Langmuir technique may lead to novel routes for
      designing cellulosic-based thin films and membranes. 

PMID- 24295323
TI  - The convergence of personality disorder diagnoses across different methods among
      monolingual (Spanish-speaking only) Hispanic patients in substance use treatment.
AB  - Methods for diagnosing personality disorders (PDs) within clinical settings
      typically diverge from those used in treatment research. Treatment groups in
      research studies are routinely diagnosed using semistructured interviews or self
      report questionnaires, yet these methods show poor agreement with clinical
      diagnoses recorded in medical charts or assigned by treating clinicians, reducing
      the potential for evidence-based practice. Furthermore, existing research has
      been limited by focusing on primarily White and English-speaking participants.
      Our study extended prior research by comparing 4 independent methods of PD
      diagnosis, including self-report questionnaire, semistructured interview, chart
      diagnoses, and ratings by treating clinicians, within a clinical series of 130
      monolingual (Spanish only) Hispanic persons (69% male; M age 37.4), in treatment
      for substance use. The authors examined the convergence of the Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; DSM-IV) PD diagnoses across
      these methods. PD diagnoses appeared infrequently within medical charts but were
      diagnosed at higher levels by independent treating clinicians, self-report
      questionnaires, and semistructured interviews. Nonetheless, diagnostic
      concordance between clinical diagnoses and the other methods were poor (kappa <
      .20). Convergence of PD diagnoses across diagnostic methods for Spanish-speaking
      Hispanic persons are comparable to other groups allaying concerns about cross
      cultural application of PD diagnoses. Additionally, the results of this study
      echo previous research in suggesting that clinicians' PD diagnoses overlap little
      with self-report questionnaires or semistructured diagnostic interviews and
      suggest that PDs are underdiagnosed using standard diagnostic approaches.
      Implications for the clinical application of empirically supported research are
      discussed.

PMID- 24295324
TI  - Inhibition of the growth of colorado potato beetle larvae by macrocypins,
      protease inhibitors from the parasol mushroom.
AB  - Proteins from higher fungi have attracted interest because of their exceptional
      characteristics. Macrocypins, cysteine protease inhibitors from the parasol
      mushroom Macrolepiota procera , were evaluated for their adverse effects and
      their mode of action on the major potato pest Colorado potato beetle (CPB,
      Leptinotarsa decemlineata Say). They were shown to reduce larval growth when
      expressed in potato or when their recombinant analogues were added to the diet.
      Macrocypins target a specific set of digestive cysteine proteases, intestains.
      Additionally, protein-protein interaction analysis revealed potential targets
      among other digestive enzymes and proteins related to development and primary
      metabolism. No effect of dietary macrocypins on gene expression of known
      adaptation-related digestive enzymes was observed in CPB guts. Macrocypins are
      the first fungal protease inhibitors to be reported as having a negative effect
      on growth and development of CPB larvae and could also be evaluated as control
      agents for other pests. 

PMID- 24295326
TI  - A detailed investigation on the interactions between magnetic nanoparticles and
      cell membrane models.
AB  - The understanding of the interactions between small molecules and magnetic
      nanoparticles is of great importance for many areas of bioapplications. Although
      a large array of studies in this area have been performed, aspects involving the
      interaction of magnetic nanoparticles with phospholipids monolayers, which can
      better mimic biological membranes, have not yet been clarified. This study was
      aimed at investigating the interactions between Langmuir films of dipalmitoyl
      phosphatidylglycerol and dipalmitoyl phosphatidylcholine, obtained on an aqueous
      subphase, and magnetic nanoparticles. Sum-frequency generation (SFG) vibrational
      spectroscopy was used to verify the orientation and molecular conformation and to
      better understand the interactions between phospholipids and the magnetic
      nanoparticles. Surface pressure-area isotherms and SFG spectroscopy made it
      possible to investigate the interaction of these nanomaterials with components of
      phospholipids membranes at the water surface. 

PMID- 24295327
TI  - Targeting the type III secretion system to treat bacterial infections.
AB  - INTRODUCTION: Causative agents of pneumonia, gastroenteritis, typhoid fever, and
      plague all utilize a type III secretion system (T3SS) to directly inject proteins
      into human cells and cause disease. These bacterial pathogens are frequently
      resistant to antibiotics and novel treatment options are needed. The T3SS is
      essential for virulence and can be inhibited to prevent disease. AREAS COVERED:
      T3SS structure and assembly are introduced in this review, highlighting targets
      for T3SS-specific therapeutics. Promising inhibitors of type III secretion (T3S),
      their modes of action, and successful techniques for their identification are
      reviewed. T3S inhibitor research has focused on small molecules identified in
      high-throughput screens, although recently inhibitors have also been identified
      or engineered by rational design. Promising compounds have emerged that inhibit
      T3S and attenuate virulence in several pathogens, including an engineered
      antibody in clinical trials. T3S inhibitor research may yield effective
      treatments and prophylactics that are effective against a wide range of human
      pathogens. EXPERT OPINION: More techniques are needed to identify the mode of
      action for compounds identified in high-throughput screens, a long-standing
      challenge. Although only a few groups have attempted rational design of
      inhibitors, the approach has seen initial success and mechanistic follow-up
      studies are greatly simplified.

PMID- 24295325
TI  - Discrimination of potent inhibitors of Toxoplasma gondii enoyl-acyl carrier
      protein reductase by a thermal shift assay.
AB  - Many microbial pathogens rely on a type II fatty acid synthesis (FASII) pathway
      that is distinct from the type I pathway found in humans. Enoyl-acyl carrier
      protein reductase (ENR) is an essential FASII pathway enzyme and the target of a
      number of antimicrobial drug discovery efforts. The biocide triclosan is
      established as a potent inhibitor of ENR and has been the starting point for
      medicinal chemistry studies. We evaluated a series of triclosan analogues for
      their ability to inhibit the growth of Toxoplasma gondii, a pervasive human
      pathogen, and its ENR enzyme (TgENR). Several compounds that inhibited TgENR at
      low nanomolar concentrations were identified but could not be further
      differentiated because of the limited dynamic range of the TgENR activity assay.
      Thus, we adapted a thermal shift assay (TSA) to directly measure the dissociation
      constant (Kd) of the most potent inhibitors identified in this study as well as
      inhibitors from previous studies. Furthermore, the TSA allowed us to determine
      the mode of action of these compounds in the presence of the reduced nicotinamide
      adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide (NAD+) cofactor.
      We found that all of the inhibitors bind to a TgENR-NAD+ complex but that they
      differed in their dependence on NAD+ concentration. Ultimately, we were able to
      identify compounds that bind to the TgENR-NAD+ complex in the low femtomolar
      range. This shows how TSA data combined with enzyme inhibition, parasite growth
      inhibition data, and ADMET predictions allow for better discrimination between
      potent ENR inhibitors for the future development of medicine.

PMID- 24295328
TI  - Spectral tuning of ultraviolet cone pigments: an interhelical lock mechanism.
AB  - Ultraviolet (UV) cone pigments can provide insights into the molecular evolution
      of vertebrate vision since they are nearer to ancestral pigments than the dim
      light rod photoreceptor rhodopsin. While visible-absorbing pigments contain an 11
      cis retinyl chromophore with a protonated Schiff-base (PSB11), UV pigments
      uniquely contain an unprotonated Schiff-base (USB11). Upon F86Y mutation in model
      UV pigments, both the USB11 and PSB11 forms of the chromophore are found to
      coexist at physiological pH. The origin of this intriguing equilibrium remains to
      be understood at the molecular level. Here, we address this phenomenon and the
      role of the USB11 environment in spectral tuning by combining mutagenesis studies
      with spectroscopic (UV-vis) and theoretical [DFT-QM/MM (SORCI+Q//B3LYP/6-31G(d):
      Amber96)] analysis. We compare structural models of the wild-type (WT), F86Y,
      S90A and S90C mutants of Siberian hamster ultraviolet (SHUV) cone pigment to
      explore structural rearrangements that stabilize USB11 over PSB11. We find that
      the PSB11 forms upon F86Y mutation and is stabilized by an "inter-helical lock"
      (IHL) established by hydrogen-bonding networks between transmembrane (TM) helices
      TM6, TM2, and TM3 (including water w2c and amino acid residues Y265, F86Y, G117,
      S118, A114, and E113). The findings implicate the involvement of the IHL in
      constraining the displacement of TM6, an essential component of the activation of
      rhodopsin, in the spectral tuning of UV pigments. 

PMID- 24295329
TI  - Estimations of water balance after validating and administering the water balance
      questionnaire in pregnant women.
AB  - Dehydration during pregnancy may be harmful for the mother and fetus; thus our
      objective was to understand whether pregnant women balance water intake and loss.
      The Water Balance Questionnaire (WBQ) was modified to reflect pregnancy (WBQ-P).
      Validation was performed using 3-day diaries (n = 60) and hydration indices in
      urine (osmolality, specific gravity, pH and color, n = 40). The WBQ-P was found
      valid according to Kedhal tau-b coefficient agreement. The WBQ-P was administered
      to 95, 100 and 97 women per trimester, in Greece. Median (IQR) water balance,
      intake and loss were, respectively, 203 (-577, 971), 2917 (2187, 3544) and 2658
      (2078, 3391) ml/day; these did not differ among the trimesters or between
      pregnant and non-pregnant women. However, more pregnant women were falling in the
      higher quartiles of water balance distribution. No differences in sources of
      water intake were identified except that women in the third trimester had lower
      water intake from beverages.

PMID- 24295330
TI  - Spontaneous subperiosteal orbital hematoma as initial presentation of metastatic
      lung adenocarcinoma to the skull: case report.
AB  - INTRODUCTION: Subperiosteal orbital hematoma is a rare occurrence, typically
      developing as a result of orbital trauma. The spontaneous formation of a
      subperiosteal orbital hematoma (sSOH) may also occur but is less frequent. To
      date there has been no documented cases of sSOH as the initial presentation of an
      unknown metastatic neoplasm to the skull. We provide a case of a woman with
      unknown lung adenocarcinoma that metastasized to the skull which caused the
      formation of a sSOH resulting in orbital compression syndrome. CASE REPORT: A 57
      year-old female presented with double vision, retro-orbital right eye pain, and
      vision loss in the right eye. A magnetic resonance imaging revealed a right
      orbital compressive lesion with an adjacent supraorbital skull lesion and
      separate left frontal skull lesion. Intra-operative findings along with post
      operative immunohistochemistry staining revealed sSOH resulting from a metastatic
      lung adenocarcinoma to the skull. Further metastatic work up also revealed an
      occult lung mass and multiple spinal lesions. CONCLUSION: Differential diagnosis
      of etiologies causing the formation of sSOH in an adult without history of trauma
      should include metastatic neoplasm to the skull and warrants metastatic workup.
      Treatment options of sSOH have included observation with spontaneous resolution;
      however, we opted for surgical decompression of the eye and biopsy of the skull
      mass.

PMID- 24295331
TI  - Synthetic and coordination chemistry of the heavier trivalent technetium binary
      halides: uncovering technetium triiodide.
AB  - Technetium tribromide and triiodide were obtained from the reaction of the
      quadruply Tc-Tc-bonded dimer Tc2(O2CCH3)4Cl2 with flowing HX(g) (X = Br, I) at
      elevated temperatures. At 150 and 300  degrees C, the reaction with HBr(g) yields
      TcBr3 crystallizing with the TiI3 structure type. The analogous reactions with
      flowing HI(g) yield TcI3, the first technetium binary iodide to be reported.
      Powder X-ray diffraction (PXRD) measurements show the compound to be amorphous at
      150  degrees C and semicrystalline at 300  degrees C. X-ray absorption fine
      structure spectroscopy indicates TcI3 to consist of face-sharing TcI6 octahedra.
      Reactions of technetium metal with elemental iodine in a sealed Pyrex ampules in
      the temperature range 250-400  degrees C were performed. At 250  degrees C, no
      reaction occurred, while the reaction at 400  degrees C yielded a product whose
      PXRD pattern matches the one of TcI3 obtained from the reaction of
      Tc2(O2CCH3)4Cl2 and flowing HI(g). The thermal stability of TcBr3 and TcI3 was
      investigated in Pyrex and/or quartz ampules at 450  degrees C under vacuum.
      Technetium tribromide decomposes to Na{[Tc6Br12]2Br} in a Pyrex ampule and to
      technetium metal in a quartz ampule; technetium triiodide decomposes to
      technetium metal in a Pyrex ampule. 

PMID- 24295332
TI  - Ultrafast energy transfer between molecular assemblies and surface plasmons in
      the strong coupling regime.
AB  - The nonlinear optical dynamics of nanomaterials comprised of plasmons interacting
      with quantum emitters is investigated by a self-consistent model based on the
      coupled Maxwell-Liouville-von Neumann equations. It is shown that ultrashort
      resonant laser pulses significantly modify the optical properties of such hybrid
      systems. It is further demonstrated that the energy transfer between interacting
      molecules and plasmons occurs on a femtosecond time scale and can be controlled
      with both material and laser parameters. 

PMID- 24295333
TI  - Protein secretome of moss plants (Physcomitrella patens) with emphasis on changes
      induced by a fungal elicitor.
AB  - Studies on extracellular proteins (ECPs) contribute to understanding of the
      multifunctional nature of apoplast. Unlike vascular plants (tracheophytes),
      little information about ECPs is available from nonvascular plants, such as
      mosses (bryophytes). In this study, moss plants (Physcomitrella patens) were
      grown in liquid culture and treated with chitosan, a water-soluble form of chitin
      that occurs in cell walls of fungi and insects and elicits pathogen defense in
      plants. ECPs released to the culture medium were compared between chitosan
      treated and nontreated control cultures using quantitative mass spectrometry
      (Orbitrap) and 2-DE-LC-MS/MS. Over 400 secreted proteins were detected, of which
      70% were homologous to ECPs reported in tracheophyte secretomes. Bioinformatics
      analyses using SignalP and SecretomeP predicted classical signal peptides for
      secretion (37%) or leaderless secretion (27%) for most ECPs of P. patens, but
      secretion of the remaining proteins (36%) could not be predicted using
      bioinformatics. Cultures treated with chitosan contained 72 proteins not found in
      untreated controls, whereas 27 proteins found in controls were not detected in
      chitosan-treated cultures. Pathogen defense-related proteins dominated in the
      secretome of P. patens, as reported in tracheophytes. These results advance
      knowledge on protein secretomes of plants by providing a comprehensive account of
      ECPs of a bryophyte. 

PMID- 24295334
TI  - Solid-phase flexibility in Ag2Se semiconductor nanocrystals.
AB  - Nanocrystals are known to alter the relative stability of bulk solid phases. Here
      we test the limits of this effect on Ag2Se nanocrystals, a promising new
      electronic and infrared material. In the bulk, Ag2Se exhibits a solid-solid phase
      transition to a superionic conducting phase at moderate temperatures. We map this
      phase transition as a function of size, temperature, and surface treatment in
      Ag2Se core-only and core-shell nanocrystals. We show that the transition can be
      tuned not just below but also above the bulk phase-transition temperature. This
      phase flexibility has implications for applications in optoelectronic and phase
      memory devices. 

PMID- 24295335
TI  - Six-month follow-up study of health markers of nanomaterials among workers
      handling engineered nanomaterials.
AB  - The aim of this study was to identify the health hazards and possible exposure
      surveillance markers of workers exposed to nanoparticles during manufacturing and
      application in comparison to a group of unexposed workers. For this longitudinal
      study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers
      from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial
      handling workers and 77 unexposed workers were monitored 6 months later. We
      investigated pulmonary and cardiovascular disease markers, inflammation and
      oxidative stress markers, antioxidant enzymes and genotoxicity markers.
      Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and
      cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were
      significantly associated with nanomaterial-handling during the 6-month follow-up
      period. In addition, the small airway damage marker (Clara cell protein 16) and
      lung function test parameters were also significantly associated with handling
      nanomaterials. The study markers and lung function tests are possible markers
      that could be useful for surveillance of nanomaterial-handling workers.

PMID- 24295336
TI  - Palladium-catalyzed alpha-arylation of benzylic phosphine oxides.
AB  - A novel approach to prepare diarylmethyl phosphine oxides from benzyl phosphine
      oxides via deprotonative cross-coupling processes (DCCP) is reported. The
      optimization of the reaction was guided by High-Throughput Experimentation (HTE)
      techniques. The Pd(OAc)2/Xantphos-based catalyst enabled the reaction between
      benzyl diphenyl or dicyclohexyl phosphine oxide derivatives and aryl bromides in
      good to excellent yields (51-91%). 

PMID- 24295337
TI  - Using read codes to identify patients with irritable bowel syndrome in general
      practice: a database study.
AB  - BACKGROUND: Estimates of the prevalence of irritable bowel syndrome (IBS) vary
      widely, and a large proportion of patients report having consulted their general
      practitioner (GP). In patients with new onset gastrointestinal symptoms in
      primary care it might be possible to predict those at risk of persistent
      symptoms. However, one of the difficulties is identifying patients within primary
      care. GPs use a variety of Read Codes to describe patients presenting with IBS.
      Furthermore, in a qualitative study, exploring GPs' attitudes and approaches to
      defining patients with IBS, GPs appeared reluctant to add the IBS Read Code to
      the patient record until more serious conditions were ruled out. Consequently,
      symptom codes such as 'abdominal pain', 'diarrhoea' or 'constipation' are used.
      The aim of the current study was to investigate the prevalence of recorded
      consultations for IBS and to explore the symptom profile of patients with IBS
      using data from the Salford Integrated Record (SIR). METHODS: This was a database
      study using the SIR, a local patient sharing record system integrating primary,
      community and secondary care information. Records were obtained for a cohort of
      patients with gastrointestinal disorders from January 2002 to December 2011.
      Prevalence rates, symptom recording, medication prescribing and referral patterns
      were compared for three patient groups (IBS, abdominal pain (AP) and Inflammatory
      Bowel Disease (IBD)). RESULTS: The prevalence of IBS (age standardised rate: 616
      per year per 100,000 population) was much lower than expected compared with that
      reported in the literature. The majority of patients (69%) had no
      gastrointestinal symptoms recorded in the year prior to their IBS. However a
      proportion of these (22%) were likely to have been prescribed NICE guideline
      recommended medications for IBS in that year. The findings for AP and IBD were
      similar. CONCLUSIONS: Using Read Codes to identify patients with IBS may lead to
      a large underestimate of the community prevalence. The IBS diagnostic Read Code
      was rarely applied in practice. There are similarities with many other medically
      unexplained symptoms which are typically difficult to diagnose in clinical
      practice.

PMID- 24295338
TI  - Improvement of therapeutic index for brain tumors with daily image guidance.
AB  - BACKGROUND: Image-guidance maximizes the therapeutic index of brain irradiation
      by decreasing setup uncertainty. As dose-volume data emerge defining the
      tolerance of critical normal structures responsible for neuroendocrine function
      and neurocognition, minimizing clinical target volume (CTV) to planning target
      volume (PTV) expansion of targets near these structures potentially lessens long
      term toxicity. METHODS: We reviewed the treatment records of 29 patients with
      brain tumors, with a total of 517 fractions analyzed. The CTV was uniformly
      expanded by 3 mm to create the PTV for all cases. We determined the effect of
      patient specific factors (prescribed medications, weight gain, tumor location)
      and image-guidance technique on setup uncertainty and plotted the mean +/-
      standard deviation for each factor. ANOVA was used to determine significance
      between these factors on setup uncertainty. We determined the impact of applying
      the initial three fraction variation as custom PTV-expansion on dose to normal
      structures. RESULTS: The initial 3 mm margin encompassed 88% of all measured
      shifts from daily imaging for all fractions. There was no difference (p = n.s.)
      in average setup uncertainty between CBCT or kV imaging for all patients.
      Vertical, lateral, longitudinal, and 3D shifts were similar (p = n.s.) between
      days 1, 2, and 3 imaging and later fractions. Patients prescribed sedatives
      experienced increased setup uncertainty (p < 0.05), while weight gain,
      corticosteroid administration, and anti-seizure medication did not associate with
      increased setup uncertainty. Patients with targets near OAR with individualized
      margins led to decreased OAR dose. No reductions to targets occurred with
      individualized PTVs. CONCLUSIONS: Daily imaging allows application of
      individualized CTV expansion to reduce dose to OAR responsible for
      neurocognition, learning, and neuroendocrine function below doses shown to
      correlate with long-term morbidity. The demonstrated reduction in dose to OAR in
      this study has implications for quality of life and provides the motivation to
      pursue custom PTV expansion.

PMID- 24295339
TI  - Translation and validation of the German version of the Bournemouth questionnaire
      for low back pain.
AB  - BACKGROUND: Finding the best outcome measures for research and quality assurance
      purposes in terms of validity, sensitivity to change, length and ease of
      completion is crucial. The Bournemouth questionnaire for neck pain patients was
      recently translated and validated into German and found to be more sensitive to
      change than other commonly used questionnaires. However, the low back pain
      version is not yet available in German. Therefore the purpose of this study was
      to translate and validate the Bournemouth Questionnaire (BQ) for low back pain
      (LBP) into German. METHODS: The translation was done in 4 steps, translated and
      back-translated by two independent people and adapted and approved by an expert
      committee. Face validity was then done by 30 people who checked the questionnaire
      for comprehension. Test-retest reliability (reproducibility) was tested using 30
      stable back pain patients. Internal consistency was tested using 108 low back
      patients. External construct validity, external longitudinal validity and
      responsiveness was tested against the German versions of the Oswestry Disability
      Index (ODI) and the SF-36 questionnaire using 108 patients from 5 different
      chiropractic clinics. RESULTS: The BQ showed high test-retest reliability (ICC >
      0.91) for all items and strong internal consistency (Cronbachs alpha = 0.86 at
      baseline and 0.94 at 4 weeks). CONCLUSION: The BQ for LBP was successfully
      translated and adapted into German. It was successfully tested for validity,
      consistency, and responsiveness against the German versions of the ODI and the SF
      36. It is shorter, covers more domains than the ODI and is more sensitive to
      change than the other questionnaires.

PMID- 24295340
TI  - Reduction of earth alkaline metal salts in THF solution studied by picosecond
      pulse radiolysis.
AB  - Picosecond pulse radiolysis of tetrahydrofuran (THF) solutions containing earth
      alkaline metal salt, M(II)(ClO4)2, at different concentrations are performed
      using two different supercontinua as probe pulse, one covering the visible and
      another the near-infrared (NIR) down to the visible. Two types of line scan
      detectors are used to record the absorption spectra in the range from 400 to 1500
      nm. Because of the strong overlap between the spectra of the absorbing species in
      the present wavelength range, global matrices were built for each M(II) system,
      by delay-wise binding the matrix for pure THF with the available matrices for
      this cation. The number of absorbers was assessed by Singular Value Decomposition
      of the global matrix, and a MCR-ALS analysis with the corresponding number of
      species was performed. The analysis of the results show clearly that solvated
      electron reacts with the earth alkaline metal molecule and the product has an
      optical absorption band very different than that of solvated electron in pure
      THF. So, contrarily to the case of solution containing free Na(+), in the
      presence of Mg(II), Ca(II) and Sr(II) the observed absorption band is not only
      blueshifted, but its shape is also drastically changed. In fact with Na(+)
      solvated electron forms a tight-contact pair but with earth alkaline metal cation
      solvated electron is scavenged by the undissociated molecule M(II)(ClO4)2. In
      order to determine the structure of the absorbing species observed after the
      electron pulse, Monte Carlo/DFT simulations were performed in the case of Mg(II),
      based on a classical Monte Carlo code and DFT/PCM calculation of the solute. The
      UV-visible spectrum of the solute is calculated with the help of the TDDFT
      method. The calculated spectrum is close to the experimental one. It is due to
      two species, a contact pair and an anion. 

PMID- 24295342
TI  - Transparent conductive oxide films mixed with gallium oxide nanoparticle/single
      walled carbon nanotube layer for deep ultraviolet light-emitting diodes.
AB  - We propose a transparent conductive oxide electrode scheme of gallium oxide
      nanoparticle mixed with a single-walled carbon nanotube (Ga2O3 NP/SWNT) layer for
      deep ultraviolet light-emitting diodes using spin and dipping methods. We
      investigated the electrical, optical and morphological properties of the Ga2O3
      NP/SWNT layers by increasing the thickness of SWNTs via multiple dipping
      processes. Compared with the undoped Ga2O3 films (current level 9.9 * 10-9 A @ 1
      V, transmittance 68% @ 280 nm), the current level flowing in the Ga2O3 NP/SWNT
      increased by approximately 4 * 105 times and the transmittance improved by 9%
      after 15 times dip-coating (current level 4 * 10-4 A at 1 V; transmittance 77.0%
      at 280 nm). These improvements result from both native high transparency of Ga2O3
      NPs and high conductivity and effective current spreading of SWNTs. 

PMID- 24295343
TI  - Anatomy of the neck.

PMID- 24295341
TI  - Nitrosative stress induces peroxiredoxin 1 ubiquitination during ischemic insult
      via E6AP activation in endothelial cells both in vitro and in vivo.
AB  - AIMS: Although there is accumulating evidence that increased formation of
      reactive nitrogen species in cerebral vasculature contributes to the progression
      of ischemic damage, but the underlying molecular mechanisms remain elusive.
      Peroxiredoxin 1 (Prx1) can initiate the antioxidant response by scavenging free
      radicals. Therefore, we tested the hypothesis that Prx1 regulates the
      susceptibility to nitrosative stress damage during cerebral ischemia in vitro and
      in vivo. RESULTS: Proteomic analysis in endothelial cells revealed that Prx1 was
      upregulated after stress-related oxygen-glucose deprivation (OGD). Although
      peroxynitrite upregulated Prx1 rapidly, this was followed by its
      polyubiquitination within 6 h after OGD mediated by the E3 ubiquitin ligase E6
      associated protein (E6AP). OGD colocalized E6AP with nitrotyrosine in endothelial
      cells. To assess translational relevance in vivo, mice were studied after middle
      cerebral artery occlusion (MCAO). This was accompanied by Prx1 ubiquitination and
      degradation by the activation of E6AP. Furthermore, brain delivery of a
      lentiviral vector encoding Prx1 in mice inhibited blood-brain barrier leakage and
      neuronal damage significantly following MCAO. INNOVATION AND CONCLUSIONS:
      Nitrosative stress during ischemic insult activates E6AP E3 ubiquitin ligase that
      ubiquitinates Prx1 and subsequently worsens cerebral damage. Thus, targeting the
      Prx1 antioxidant defense pathway may represent a novel treatment strategy for
      neurovascular protection in stroke.

PMID- 24295344
TI  - Nonsurgical neck laxity correction.

PMID- 24295345
TI  - Nonexcisional, minimally invasive rejuvenation of the neck.

PMID- 24295346
TI  - Progressive tunnelizations in neck face lift detachment.

PMID- 24295347
TI  - Lore's fascia a strong fixation point for neck rejuvenation procedures.

PMID- 24295348
TI  - Restoring the neck contour.

PMID- 24295349
TI  - Open neck contouring.

PMID- 24295350
TI  - The LOPP-lateral overlapping plication of the platysma: an effective neck lift
      without submental incision.

PMID- 24295351
TI  - Total neck rejuvenation using a modified Fogli approach and selective resection
      of anterior platysmal bands.

PMID- 24295352
TI  - Neck contouring.

PMID- 24295353
TI  - Managing the components of the aging neck: from liposuction to submentalplasty,
      to neck lift.

PMID- 24295354
TI  - Multidimensional evaluation and surgical approaches to neck rejuvenation.

PMID- 24295355
TI  - Neck rejuvenation with suture suspension platysmaplasty technique: a minimally
      invasive neck lift technique that addresses all patients' anatomic needs.

PMID- 24295356
TI  - Rejuvenation of the aging neck: 40 years experience.

PMID- 24295357
TI  - Serendipity in ultimate neck lift correction.

PMID- 24295358
TI  - Neck lift technique: the Lifestyle Lift.

PMID- 24295359
TI  - Preface. The neck: a complex cylinder.

PMID- 24295360
TI  - Constrained prose recall and the assessment of long-term forgetting: the case of
      ageing and the Crimes Test.
AB  - It has become increasingly clear that some patients with apparently normal memory
      may subsequently show accelerated long-term forgetting (ALF), with dramatic loss
      when retested. We describe a constrained prose recall task that attempts to lay
      the foundations for a test suitable for detecting ALF sensitively and
      economically. Instead of the usual narrative structure of prose recall tests, it
      employs a matrix structure involving four episodes, each describing a minor
      crime, with each crime involving the binding into a coherent episode of a
      specified range of features, involving the victim, the crime, the criminal and
      the location, allowing a total of 80 different probed recall questions to be
      generated. These are used to create four equivalent 20-item tests, three of which
      are used in the study. After a single verbal presentation, young and elderly
      participants were tested on three occasions, immediately, and by telephone after
      a delay of 6 weeks, and at one of a varied range of intermediate points. The
      groups were approximately matched on immediate test; both showed systematic
      forgetting which was particularly marked in the elderly. We suggest that
      constrained prose recall has considerable potential for the study of long-term
      forgetting.

PMID- 24295361
TI  - An unusual case with vasculo-Behcet's disease: peripheral arterial aneurysm in an
      elderly woman.
AB  - Behcet's disease (BD) is a chronic, multi-systemic disorder that can affect all
      sizes of arteries and veins. Vascular involvement of BD is generally observed in
      young men and is an important cause of morbidity and mortality. Arterial lesions
      can appear as aneurysms, stenosis and occlusions in BD. We, here, present the
      case of a woman who developed a peripheral arterial aneurysm in her sixth decade,
      20 years after disease onset. BD patients with aneurysms should be consulted at
      any age for pre- and post-operative assessment for immunosuppressive treatment to
      reduce recurrences, complications and disease activation. 

PMID- 24295362
TI  - Predictors of performance of students in biochemistry in a doctor of chiropractic
      curriculum.
AB  - Objective : This study investigated the effect of completion of course
      prerequisites, undergraduate grade point average (GPA), undergraduate degree, and
      study habits on the performance of students in the biochemistry course at Palmer
      College of Chiropractic Florida. Methods : Students self-reported information
      regarding academic preparation at the beginning of the semester using a
      questionnaire. Final exam grade and final course grade were noted and used as
      measures of performance. Multivariate analysis of variance was used to determine
      if number of prerequisites completed, undergraduate GPA, undergraduate degree,
      hours spent studying in undergraduate study, and hours spent studying in the
      first quarter of the chiropractic program were associated significantly with the
      biochemistry final exam grade or the final grade for the biochemistry course.
      Results : The number of prerequisites completed, undergraduate degree, hours
      spent studying in undergraduate study, and hours spent studying in the first
      quarter of the chiropractic program did not significantly affect the biochemistry
      final exam grade or the final grade for the biochemistry course, but
      undergraduate GPA did. Subsequent univariate analysis and Tukey's post hoc
      comparisons revealed that students with an undergraduate GPA in the 3.5 to 3.99
      range earned significantly higher final course grades than students with an
      undergraduate GPA in the 2.5 to 2.99 range. Conclusion : No single variable was
      determined to be a factor that determines student success in biochemistry. The
      interrelationship between the factors examined warrants further investigation to
      understand fully how to predict the success of a student in the biochemistry
      course. 

PMID- 24295363
TI  - Publication rates of abstracts presented at the Association of Chiropractic
      Colleges Educational Conference/Research Agenda Conference from 2002 to 2008.
AB  - Objective : The purposes of this study were to investigate the overall
      publication rates of presentations at the Association of Chiropractic Colleges
      Educational Conference/Research Agenda Conference (ACC/RAC) meetings (2002-2008),
      differences in the publication rates of platform vs poster presentations, and the
      consistency of the meeting abstract compared to the full-length journal article.
      Methods : Abstracts were obtained from proceedings published in the Journal of
      Chiropractic Education. Literature searches using PubMed and the Index to the
      Chiropractic Literature (ICL) were performed to locate peer-reviewed journal
      articles based upon those abstracts. Whether the article was based upon a poster
      or platform presentation, and the congruence of the information in the abstract
      and article were recorded. Results : We identified 776 proceeding abstracts, 249
      of which eventually were published between 2002 and 2012. The overall publication
      rate was 32.2%. A total of 42.7% of platform presentations eventually were
      published vs 20.3% of posters. Congruency showed that 43.2% had the same title as
      the meeting abstract, 59.7% had the same authorship, and 88.8% had the same
      methods. Conclusion : Publication rates of abstracts from spine and orthopedic
      surgery national meetings range from 34% to 59%. The ACC/RAC meetings have
      similar publication rates. More platform than poster presentations reach full
      publication. The congruency of ACC/RAC abstracts to published articles is higher
      than national meetings in other fields. 

PMID- 24295365
TI  - Phenol-soluble modulins: novel virulence-associated peptides of staphylococci.
AB  - Phenol-soluble modulins (PSMs), a novel class of small peptides with an
      amphipathic alpha-helical structure and strong surfactant-like properties, are
      produced by most staphylococci, especially pathogenic Staphylococcus aureus and
      Staphylococcus epidermidis. PSMs can: induce the production of proinflammatory
      cytokines; recruit, activate and lyse neutrophils to help staphylococci evade
      immune damage; lyse erythrocytes and are associated with the hemolysis of
      staphylococcal disease; facilitate the structuring and detachment of
      staphylococcal biofilms and disseminate biofilm-associated infection; and kill
      competing microbes and act as weapons in interbacterial warfare. Therefore, PSMs
      are considered to be critical virulence-associated factors and to play important
      roles in the pathogenesis of staphylococci. This review summarizes the
      classification, structure, expression regulation and biological functions of
      PSMs. The possible means to prevent PSM-associated diseases are also outlined in
      order to emphasize the need to investigate PSMs as potential targets for drug and
      vaccine design against staphylococcal infections. 

PMID- 24295364
TI  - Hepatocyte-like cells derived from human amniotic epithelial cells can be
      encapsulated without loss of viability or function in vitro.
AB  - Placenta derived human amniotic epithelial cells (hAEC) are an attractive source
      of stem cells for the generation of hepatocyte-like cells (HLC) for therapeutic
      applications to treat liver diseases. During hAEC differentiation into HLC, they
      become increasingly immunogenic, which may result in immune cell-mediated
      rejection upon transplantation into allogeneic recipients. Placing cells within
      devices such as alginate microcapsules can prevent immune cell-mediated
      rejection. The aim of this study was to investigate the characteristics of HLC
      generated from hAEC and to examine the effects of encapsulation on HLC viability,
      gene expression, and function. hAEC were differentiated for 4 weeks and evaluated
      for hepatocyte-specific gene expression and function. Differentiated cells were
      encapsulated in barium alginate microcapsules and cultured for 7 days and the
      effect of encapsulation on cell viability, function, and hepatocyte related gene
      expression was determined. Differentiated cells performed key functions of
      hepatocytes including urea synthesis, drug-metabolizing cytochrome P450 (CYP)3A4
      activity, indocyanine green (ICG) uptake, low-density lipoprotein (LDL) uptake,
      and exhibited glutathione antioxidant capacity. A number of hepatocyte-related
      genes involved in fat, cholesterol, bile acid synthesis, and xenobiotic
      metabolism were also expressed showing that the hAEC had differentiated into HLC.
      Upon encapsulation, the HLC remained viable for at least 7 days in culture,
      continued to express genes involved in fat, cholesterol, bile acid, and
      xenobiotic metabolism and had glutathione antioxidant capacity. CYP3A4 activity
      and urea synthesis by the encapsulated HLC were higher than that of monolayer HLC
      cultures. Functional HLC can be derived from hAEC, and HLC can be encapsulated
      within alginate microcapsules without losing viability or function in vitro. 

PMID- 24295366
TI  - Kinetic and structural evaluation of selected active site mutants of the
      Aspergillus fumigatus KDNase (sialidase).
AB  - Aspergillus fumigatus is an airborne fungal pathogen. We previously cloned and
      characterized an exo-sialidase from A. fumigatus and showed that it preferred 2
      keto-3-deoxynononic acid (KDN) as a substrate to N-acetylneuraminic acid
      (Neu5Ac). The purpose of this study was to investigate the structure-function
      relationships of critical catalytic site residues. Site-directed mutagenesis was
      used to create three mutant recombinant enzymes: the catalytic nucleophile
      (Y358H), the general acid/base catalyst (D84A), and an enlargement of the binding
      pocket to attempt to accommodate the N-acetyl group of Neu5Ac (R171L). Crystal
      structures for all enzymes were determined. The D84A mutation had an effect in
      decreasing the activity of AfKDNase that was stronger than that of the same
      mutation in the structurally similar sialidase from the bacterium Micromonospora
      viridifaciens. These data suggest that the catalytic acid is more important in
      the reaction of AfKDNase and that catalysis is less dependent on nucleophilic or
      electrostatic stabilization of the developing positive charge at the transition
      state for hydrolysis. Removal of the catalytic nucleophile (Y358H) significantly
      lowered the activity of the enzyme, but this mutant remained a retaining
      glycosidase as demonstrated by nuclear magnetic resonance spectroscopic analysis.
      This is a novel finding that has not been shown with other sialidases. Kinetic
      activity measured at pH 5.2 revealed that R171L had higher activity on a Neu5Ac
      based substrate than wild-type KDNase; hence, leucine in place of arginine in the
      binding pocket improved catalysis toward Neu5Ac substrates. Hence, whether a
      sialidase is primarily a KDNase or a neuraminidase is due in part to the presence
      of an amino acid that creates a steric clash with the N-acetyl group. 

PMID- 24295367
TI  - Verbenone structural analogues isolated from Artemesia aucheri as natural
      acaricides against Dermatophagoides spp. and Tyrophagus putrescentiae.
AB  - The acaricidal activities of Artemisia aucheri oil and (1S)-(-)-verbenone
      structural analogues were evaluated using a fumigant method against
      Dermatophagoides farinae , Dermatophagoides pteronyssinus , and Tyrophagus
      putrescentiae and then compared to those of benzyl benzoate. On the basis of the
      LD50 values against D. farinae , (1S)-(-)-verbenone (1.38 MUg/cm(2)) was about
      7.4 times more active than benzyl benzoate (10.15 MUg/cm(2)), followed by (+)
      trans-myrtanol (2.27 MUg/cm(2)), (-)-trans-myrtanol (2.30 MUg/cm(2)), and A.
      aucheri oil (8.75 MUg/cm(2)). (1S)-(-)-Verbenone (1.25 MUg/cm(2)) was
      approximately 7.8 times more effective against D. pteronyssinus than benzyl
      benzoate (9.80 MUg/cm(2)), followed by (+)-trans-myrtanol (2.18 MUg/cm(2)), (-)
      trans-myrtanol (2.22 MUg/cm(2)), and A. aucheri oil (8.46 MUg/cm(2)). In the case
      of T. putrescentiae , (1S)-(-)-verbenone (3.75 MUg/cm(2)) was roughly 3.5 times
      more toxic than benzyl benzoate (13.25 MUg/cm(2)), followed by (+)-trans-myrtanol
      (12.57 MUg/cm(2)), (-)-trans-myrtanol (12.95 MUg/cm(2)), and A. aucheri oil
      (11.55 MUg/cm(2)). These results indicate that A. aucheri oil and (1S)-(-)
      verbenone structural analogues may be effective natural agents to control house
      dust and storage mites. 

PMID- 24295368
TI  - A Meta-analysis of the relation between chemokine receptor 5 delta32 polymorphism
      and multiple sclerosis susceptibility.
AB  - OBJECTIVE: The aim of this study was to determine whether the functional
      chemokine receptor 5 delta32 (CCR5-Delta32) polymorphism is associated with
      multiple sclerosis (MS) susceptibility. METHODS: Meta-analysis was conducted to
      determine the association between the CCR5-Delta32 polymorphism and overall
      incidence of MS as well frequency of relapsing-remitting (RR), primary
      progressive (PP), and secondary progressive (SP) MS subtypes. RESULTS: In total,
      3869 subjects from eight studies (MS 1666, controls 2203) were considered for
      meta-analysis. Meta-analysis showed no association between MS and the CCR5
      Delta32 allele polymorphism (OR=1.102, 95% CI=0.830-1.462, p=0.502) with a mean
      frequency of 11.3% in MS patients and 10.4% in controls. Stratification by
      ethnicity indicated no association between the CCR5-Delta32 allele and MS in
      Europeans (OR=0.958, 95% CI=0.811-1.132, p=0.618). Meta-analysis by the disease
      subtype showed no association between RR-MS and the CCR5-Delta32 allele
      (OR=1.234, 95% CI=0.908-1.677, p=0.178). In addition, no association was found
      between the CCR5-Delta32 polymorphism and PP or SP-MS. CONCLUSIONS: Meta-analysis
      of 3869 subjects indicates a lack of association between the CCR5-Delta32
      polymorphism and MS risk in Europeans.

PMID- 24295369
TI  - In-vitro assessment and pharmacodynamics of nimesulide incorporated Aloe vera
      transemulgel.
AB  - The aim of the investigation was to prepare nimesulide emulsion for incorporation
      in Aloe vera gel base to formulate 'nimesulide - Aloe vera transemulgel' (NAE)
      and to carryout in-vitro assessment and in-vivo anti-inflammatory studies of the
      product. Although the use of nimesulide is banned for oral administration, due to
      its potential for inducing hepatotoxicity and thrombocytopenia, the use of
      nimesulide for topical delivery is prominent in the treatment of many
      inflammatory conditions including rheumatoid arthritis. The drug loading capacity
      of transdermal gels is low for hydrophobic drugs such as nimesulide. Nimesulide
      can be effectively incorporated into emulgels (a combination of emulsion and
      gel). Aloe vera has a mild anti-inflammatory effect and in the present study Aloe
      vera gel was formulated and used as a gel base to prepare NAE. The emulgels thus
      prepared were evaluated for viscosity, pH, in-vitro permeation, stability and
      skin irritation test. In-vivo anti-inflammatory studies were performed using
      carrageenan induced hind paw edema method in Wistar rats. The results were
      compared with that of commercial nimesulide gel (CNG). From the in-vitro studies,
      effective permeation of nimesulide from NAE (53.04 %) was observed compared to
      CNG (44.72 %) at 30 min indicating better drug release from NAE. Topical
      application of the emulgel found no skin irritation. Stability studies proved the
      integrity of the formulation. The percentage of inhibition of edema was highest
      for the prepared NAE (67.4 % inhibition after 240 min) compared to CNG (59.6 %).
      From our results, it was concluded that the Aloe vera gel acts as an effective
      gel base to prepare nimesulide emulgel with high drug loading capacity (86.4 %
      drug content) compared to CNG (70.5 % drug content) with significant anti
      inflammatory effect. 

PMID- 24295370
TI  - Insights into caerulomycin A biosynthesis: a two-component monooxygenase CrmH
      catalyzed oxime formation.
AB  - The immunosuppressive agent caerulomycin A features a unique 2,2'-bipyridine core
      structure and an unusual oxime functionality. Genetic and biochemical evidence
      confirms that the oxime formation in caerulomycin A biosynthesis is catalyzed by
      CrmH, a flavin-dependent two-component monooxygenase that is compatible with
      multiple flavin reductases, from a primary amine via a N-hydroxylamine
      intermediate. Structure homologue-guided site-directed mutagenesis studies
      identify four amino acid residues that are essential for CrmH catalysis. This
      study provides the first biochemical evidence of a two-component monooxygenase
      that catalyzes oxime formation. 

PMID- 24295371
TI  - Momordica charantia and type 2 diabetes: from in vitro to human studies.
AB  - Type 2 diabetes is a growing health problem worldwide that is particularly severe
      in India and China. In these areas, bitter gourd (Momordica charantia) is a
      popular vegetable which is traditionally known to have health beneficial effects
      not only, but mainly, on diabetes. Bitter gourd could be a cheap possibility to
      help the poor in these and other countries to control their blood glucose levels.
      This review describes anti-diabetic effects of bitter gourd reported in the
      literature and discusses what still needs to be clarified for developing an
      evidence-based and safe use of the bitter gourd for diabetes. Analyses of
      bioactive compounds have shown that bitter gourd is rich in nutrients and
      phytochemicals of which some have anti-diabetic effects. Juices, powders,
      extracts, and isolated compounds have been tested in vitro and in vivo. Bitter
      gourd increases insulin secretion of the pancreas, decreases intestinal glucose
      uptake, and increases uptake and utilization of glucose in peripheral tissues.
      Although human studies with type 2 diabetics are weak in their design and/or
      results, some of the studies do indicate anti-diabetic effects in patients and
      safety for bitter gourd treatment in humans. In the future, well designed studies
      with rodents will help to understand what kind of bitter gourd variety, dosage,
      preparation, and duration of administration is optimal. Such results will help to
      design human studies which are necessary to prove the effectiveness of bitter
      gourd in patients. 

PMID- 24295372
TI  - Review of erectile dysfunction in diabetic animal models.
AB  - Erectile dysfunction (ED) is a common, male sexual disorder that has a negative
      impact on the quality of life of men and their sexual partners. The prevalence of
      ED in diabetic men is >= 50%. Animal models provide a valuable perspective in the
      investigation of ED. Most basic science studies have utilized the rodent model of
      type 1 diabetes. However, an animal model for type 2 diabetes-associated ED
      requires verification. The streptozotocin (STZ) induced type 1 diabetic model has
      contributed to significant advancement in the study of ED. A Medline search using
      the keywords "diabetic animals and ED" was performed, and available peer-reviewed
      English articles between 2007-2013 were evaluated. The proposed mechanisms for
      developing ED in diabetics include: hyperglycemia, impaired nitric oxide (NO)
      synthesis, cyclic guanosine monophosphate (cGMP) pathway dysfunction, increased
      levels of reactive free-radicals, up-regulation of the RhoA/Rho-kinase pathway,
      and neuropathic damage. The current treatment regimen of diabetes-induced ED is
      multimodal. Modification of comorbidities and, specifically, rectifying the
      underlying hyperglycemia is vital to prevent or halt progression of the disease.
      Further research on the basic mechanisms of ED and additional studies using
      better animal models of ED associated with type 1 and 2 diabetes are needed.
      Preclinical studies using the diabetic animal model will likely provide further
      insight for intervention and prevention strategies for diabetic ED treatment.

PMID- 24295373
TI  - Computational modeling as part of alternative testing strategies in the
      respiratory and cardiovascular systems: inhaled nanoparticle dose modeling based
      on representative aerosol measurements and corresponding toxicological analysis.
AB  - The objectives of modeling in this work were (a) the integration of two existing
      numerical models in order to connect external exposure to nanoparticles (NPs)
      with internal dose through inhalation, and (b) to use computational fluid
      particle dynamics (CFPD) to analyze the behavior of NPs in the respiratory and
      the cardiovascular system. Regarding the first objective, a lung transport and
      deposition model was combined with a lung clearance/retention model to estimate
      NPs dose in the different regions of the human respiratory tract and some
      adjacent tissues. On the other hand, CFPD was used to estimate particle transport
      and deposition of particles in a physiologically based bifurcation created by the
      third and fourth lung generations (respiratory system), as well as to predict the
      fate of super-paramagnetic particles suspended in a liquid under the influence of
      an external magnetic field (cardiovascular system). All the above studies showed
      that, with proper refinement, the developed computational models and
      methodologies may serve as an alternative testing strategy, replacing
      transport/deposition experiments that are expensive both in time and resources
      and contribute to risk assessment.

PMID- 24295374
TI  - The reminiscence bump in older adults' life story transitions.
AB  - Older adults' memories of events that occurred in adolescence and early adulthood
      are over-represented compared to other lifetime periods. Prior research on this
      reminiscence bump has focused on qualities of individual memories. The present
      study used a novel interview method to examine the potential role played by
      mental representations of extended lifetime periods. Older adults provided oral
      life stories, and they divided their transcribed narratives into "chapters".
      Participants' ages at chapter beginnings and endings showed pronounced
      reminiscence bumps. The results are consistent with the idea that personal
      episodes occurring near the boundaries of extended lifetime periods receive
      preferential processing that enhances long-term memory. 

PMID- 24295376
TI  - Real-world cabazitaxel safety: the Italian early-access program in metastatic
      castration-resistant prostate cancer.
AB  - AIM: Cabazitaxel is a novel taxane that is approved for use in metastatic
      castration-resistant prostate cancer based on the Phase III TROPIC study, which
      showed improved overall survival with cabazitaxel/prednisone versus
      mitoxantrone/prednisone. A global early-access program was initiated in order to
      provide early access to cabazitaxel in docetaxel-pretreated patients and to
      obtain real-world data. PATIENTS & METHODS: We report interim safety results from
      an Italian prospective, single-arm, multicenter, open-label trial of 218 patients
      receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until
      disease progression, unacceptable toxicity, investigator's decision or death.
      RESULTS: Patients completing treatment received a median of six cabazitaxel
      cycles. The most common grade 3/4 adverse events were neutropenia (33.9%),
      leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or
      nail disorders were observed. CONCLUSION: These results confirm that cabazitaxel
      has a manageable safety profile in daily clinical practice and support its use in
      patients with prostate cancer who progress during or after a docetaxel-based
      therapy.

PMID- 24295377
TI  - Tivozanib reverses multidrug resistance mediated by ABCB1 (P-glycoprotein) and
      ABCG2 (BCRP).
AB  - AIM: This study aimed to investigate the mechanism of reversal of multidrug
      resistance mediated by ABC transporters with tivozanib (AV-951 and KRN-951).
      Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors. MATERIALS &
      METHODS: ABCB1- and ABCG2-overexpressing cell lines were treated with respective
      substrate antineoplastic agents in the presence or absence of tivozanib. RESULTS:
      The results indicate that tivozanib can significantly reverse ABCB1-mediated
      resistance to paclitaxel, vinblastine and colchicine, as well as ABCG2-mediated
      resistance to mitoxantrone, SN-38 and doxorubicin. Drug efflux assays showed that
      tivozanib increased the intracellular accumulation of substrates by inhibiting
      the ABCB1 and ABCG2 efflux activity. Furthermore, at a higher concentration,
      tivozanib inhibited the ATPase activity of both ABCB1 and ABCG2 and inhibited the
      photolabeling of ABCB1 or ABCG2. CONCLUSION: We conclude that tivozanib at
      noncytotoxic concentrations has the previously unknown activity of reversing
      multidrug resistance mediated by ABCB1 and ABCG2 transporters.

PMID- 24295378
TI  - Crystal structure of Bacillus cereus class Ib ribonucleotide reductase di-iron
      NrdF in complex with NrdI.
AB  - Class Ib ribonucleotide reductases (RNRs) use a dimetal-tyrosyl radical (Y*)
      cofactor in their NrdF (beta2) subunit to initiate ribonucleotide reduction in
      the NrdE (alpha2) subunit. Contrary to the diferric tyrosyl radical (Fe(III)2-Y*)
      cofactor, which can self-assemble from Fe(II)2-NrdF and O2, generation of the
      Mn(III)2-Y* cofactor requires the reduced form of a flavoprotein, NrdIhq, and O2
      for its assembly. Here we report the 1.8 A resolution crystal structure of
      Bacillus cereus Fe2-NrdF in complex with NrdI. Compared to the previously solved
      Escherichia coli NrdI-Mn(II)2-NrdF structure, NrdI and NrdF binds similarly in
      Bacillus cereus through conserved core interactions. This protein-protein
      association seems to be unaffected by metal ion type bound in the NrdF subunit.
      The Bacillus cereus Mn(II)2-NrdF and Fe2-NrdF structures, also presented here,
      show conformational flexibility of residues surrounding the NrdF metal ion site.
      The movement of one of the metal-coordinating carboxylates is linked to the metal
      type present at the dimetal site and not associated with NrdI-NrdF binding. This
      carboxylate conformation seems to be vital for the water network connecting the
      NrdF dimetal site and the flavin in NrdI. From these observations, we suggest
      that metal-dependent variations in carboxylate coordination geometries are
      important for active Y* cofactor generation in class Ib RNRs. Additionally, we
      show that binding of NrdI to NrdF would structurally interfere with the suggested
      alpha2beta2 (NrdE-NrdF) holoenzyme formation, suggesting the potential
      requirement for NrdI dissociation before NrdE-NrdF assembly after NrdI
      activation. The mode of interactions between the proteins involved in the class
      Ib RNR system is, however, not fully resolved. 

PMID- 24295375
TI  - Developmental regulation of antioxidant enzymes and their impact on neonatal lung
      disease.
AB  - SIGNIFICANCE: Deficient antioxidant defenses and compromised ability to respond
      to oxidative stress burden the immature lung. Routine neonatal therapies can
      cause increased oxidative stress with subsequent injury to the premature lung.
      Novel therapeutic approaches to protect the premature lung are greatly needed.
      RECENT ADVANCES: Live cell imaging with targeted redox probes allows for the
      measurement of subcellular oxidative stress and for comparisons of oxidative
      stress across development. Comprehension of subcellular and cell-type-specific
      responses to oxidative stress may influence the targeting of future antioxidant
      therapies. CRITICAL ISSUES: Challenges remain in identifying the optimal cellular
      targets, degree of enzyme activity, and appropriate antioxidant therapy. Further,
      the efficacy of delivering exogenous antioxidants to specific cell types or
      subcellular compartments remains under investigation. Treatment with a
      nonselective antioxidant could unintentionally compromise cellular function or
      impact cellular defense mechanisms and homeostasis. FUTURE DIRECTIONS: Genetic
      and/or biomarker screening may identify infants at the greatest risk for
      oxidative lung injury and guide the use of more selective antioxidant therapies.
      Novel approaches to the delivery of antioxidant enzymes may allow cell type- or
      cellular organelle-specific therapy. Improved comprehension of the antioxidant
      enzyme regulation across cell type, cell compartment, gender, and developmental
      stage is critical to the design and optimization of therapy.

PMID- 24295379
TI  - The effects of system-justifying motives on endorsement of essentialist
      explanations for gender differences.
AB  - People have a fundamental motive to view their social system as just, fair, and
      good and will engage in a number of strategies to rationalize the status quo
      (Jost & Banaji, 1994). We propose that one way in which individuals may "justify
      the system" is through endorsement of essentialist explanations, which attribute
      group differences to deep, essential causes. We suggest that system-justifying
      motives lead to greater endorsement of essentialist explanations because those
      explanations portray group differences as immutable. Study 1 employed an
      established system threat manipulation. We found that activating system
      justifying motives increases both male and female participants' endorsement of
      essentialist explanations for gender differences and that this effect is mediated
      by beliefs in immutability. In Study 2, we used a goal contagion manipulation and
      found that both male and female participants primed with a system-justifying goal
      are significantly more likely to agree with essentialist explanations for gender
      differences. Study 3 demonstrated that providing an opportunity to explicitly
      reject a system threat (an alternative means of satisfying the goal to defend the
      system) attenuates system threat effects on endorsement of essentialist
      explanations, further suggesting that this process is motivated. Finally, Studies
      4a and 4b dissociated the type of cause (biological vs. social) from whether
      group differences are portrayed as mutable versus immutable and found that system
      threat increases endorsement of immutable explanations, independent of the type
      of cause.

PMID- 24295380
TI  - More is not less: greater information quantity does not diminish liking.
AB  - How does the acquisition of information about a person affect the liking of that
      person? A recent set of studies suggests that liking decreases as people acquire
      more information (Norton, Frost, & Ariely, 2007). We test this "less-is-more"
      hypothesis along with an alternative hypothesis based on information integration
      theory. According to this alternative, people average available person
      information in an unbiased manner so that the liking of a person described by a
      random sample of any number of traits from a trait universe approximates the
      degree of liking that would be obtained if all trait information were known. The
      correlation between liking and the number of traits should be zero. We present
      the results of computer simulation and 2 empirical person-judgment studies. Using
      Bayesian analyses, we find that the evidence is more consistent with the
      information-integration hypothesis than with the "less-is-more" hypothesis.

PMID- 24295381
TI  - Less is often more, but not always: additional evidence that familiarity breeds
      contempt and a call for future research.
AB  - Ullrich, Krueger, Brod, and Groschupf (2013)-using a replication of the trait
      paradigm from Norton, Frost, and Ariely (2007)-suggest that less information does
      not always equal greater liking. We first ground the current debate in a larger
      historical debate in social psychology regarding the merits of configural versus
      algebraic models of person perception. We next review (a) related research that
      has suggested that more information can in some cases lead to more liking and (b)
      a large body of "real world" data-from friendships, daters, married couples,
      employment, celebrities, and politics-that suggests that more information often
      leads to less liking. We then provide an additional replication of our "less is
      more" effect, using a slight variation of the trait-list paradigm. The existing
      data suggest a need for further integrative explorations of when familiarity
      leads to contempt or liking or has no effect.

PMID- 24295382
TI  - The development of personality extremity from childhood to adolescence: relations
      to internalizing and externalizing problems.
AB  - This study investigated the development of personality extremity (deviation of an
      average midpoint of all 5 personality dimensions together) across childhood and
      adolescence, as well as relations between personality extremity and adjustment
      problems. For 598 children (mean age at Time 1 = 7.5 years), mothers and fathers
      reported the Big Five personality dimensions 4 times across 8 years. Children's
      vector length in a 5-dimensional configuration of the Big Five dimensions
      represented personality extremity. Mothers, fathers, and teachers reported
      children's internalizing and externalizing problems at the 1st and final
      measurement. In a cohort-sequential design, we modeled personality extremity in
      children and adolescents from ages 6 to 17 years. Growth mixture modeling
      revealed a similar solution for both mother and father reports: a large group
      with relatively short vectors that were stable over time (mother reports: 80.3%;
      father reports: 84.7%) and 2 smaller groups with relatively long vectors (i.e.,
      extreme personality configuration). One group started out relatively extreme and
      decreased over time (mother reports: 13.2%; father reports: 10.4%), whereas the
      other group started out only slightly higher than the short vector group but
      increased across time (mother reports: 6.5%; father reports: 4.9%). Children who
      belonged to the increasingly extreme class experienced more internalizing and
      externalizing problems in late adolescence, controlling for previous levels of
      adjustment problems and the Big Five personality dimensions. Personality
      extremity may be important to consider when identifying children at risk for
      adjustment problems.

PMID- 24295383
TI  - Imaging the atomic surface structures of CeO2 nanoparticles.
AB  - Atomic surface structures of CeO2 nanoparticles are under debate owing to the
      lack of clear experimental determination of the oxygen atom positions. In this
      study, with oxygen atoms clearly observed using aberration-corrected high
      resolution electron microscopy, we determined the atomic structures of the (100),
      (110), and (111) surfaces of CeO2 nanocubes. The predominantly exposed (100)
      surface has a mixture of Ce, O, and reduced CeO terminations, underscoring the
      complex structures of this polar surface that previously was often
      oversimplified. The (110) surface shows "sawtooth-like" (111) nanofacets and flat
      CeO2-x terminations with oxygen vacancies. The (111) surface has an O
      termination. These findings can be extended to the surfaces of differently shaped
      CeO2 nanoparticles and provide insight about face-selective catalysis. 

PMID- 24295384
TI  - Stereocontrolled total syntheses of (+/-)-fawcettimine, (+/-)-lycoflexine, and
      (+/-)-lycoflexine N-oxide.
AB  - New stereocontrolled total syntheses of (+/-)-fawcettimine, (+/-)-lycoflexine,
      and (+/-)-lycoflexine N-oxide have been accomplished. The highlights include a
      one-pot annulation to construct the enedione and a microwave-promoted Diels-Alder
      reaction. 

PMID- 24295385
TI  - 3,6,9,12-Tetrasubstituted chrysenes: synthesis, photophysical properties, and
      application as blue fluorescent OLED.
AB  - A short synthesis of unsubstituted chrysene is described to provide a cheap
      source of this compound. This chrysene was used to prepare 3,6,9,12
      tetrabromochrysene, which was subsequently transformed into various 3,6,9,12
      tetrasubstituted chrysenes bearing four aryl, alkynyl, or amino groups by means
      of the Suzuki, Sonogashira, or Buchwald-Hartwig coupling reaction, respectively.
      These substituents result in large bathochromic shifts in the chrysene absorption
      and emission spectra. These new chrysene derivatives show blue fluorescent
      emission (401-471 nm) with high quantum yields (0.44-0.87). DFT calculations on
      these chrysenes rationalize well the substituent effects on their HOMO and LUMO
      energy levels. One representative chrysene (6g) was used as a blue fluorescent
      emitter in an OLED device that showed an outstanding external quantum efficiency
      (eta = 6.31%) with blue emission [CIE (x, y) = (0.13, 0.20)] and a low turn-on
      voltage (3.0 V). 

PMID- 24295386
TI  - Correlation between two biomarkers of atherosclerosis, osteopontin and
      angiopoietin-2, in non-diabetic ankylosing spondylitis patients undergoing TNF
      alpha antagonist therapy.
AB  - OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients
      with ankylosing spondylitis (AS) undergoing TNF-alpha antagonist-infliximab
      therapy are increased compared with controls and to establish whether disease
      activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of
      atherosclerosis are potential determinants of circulating OPN levels in these
      patients. METHODS: We assessed OPN serum concentrations in a series of 30 non
      diabetic AS patients without cardiovascular disease undergoing TNF-alpha
      antagonist-infliximab therapy and 48 matched controls. OPN levels were measured
      immediately before and after an infliximab infusion, at time 0 and at time 120
      minutes respectively. Correlations of OPN serum levels with clinical features,
      disease activity, systemic inflammation, metabolic syndrome and several
      biomarkers of atherosclerosis were assessed. Potential changes in OPN
      concentration following an infusion of anti-TNF-alpha monoclonal antibody
      infliximab were also analysed. RESULTS: At the time of the study AS patients
      undergoing anti-TNF-alpha therapy had low disease activity (mean BASDAI 2.94) and
      they showed similar OPN serum levels to healthy controls. No differences in OPN
      levels according to the specific clinical features of the disease were seen.
      Also, no correlation between OPN concentration and insulin resistance and
      adipokines was observed. However, a positive correlation between OPN and
      angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a
      single infliximab infusion led to a marginal statistically significant reduction
      in OPN levels (24112.19+/-14608.73 pg/ml at time 0 versus 21806.62+/-11390.83
      pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are
      correlated in non-diabetic AS patients undergoing TNF-alpha antagonist therapy.

PMID- 24295387
TI  - Cryoablation for a right atrial myxoma arising from the Koch's triangle: a case
      report.
AB  - A 78-year-old caucasian patient with compromised cardiac function presenting
      recurrent episodes of pulmonary embolism was referred to our center for resection
      of a voluminous right atrial myxoma arising from the Koch's triangle. To preserve
      the conduction system, we performed an excision of the myxoma associated with
      cryoablation of its stalk. This case is of special interest for discussing
      possibilities of preservation of the atrioventricular conduction system in such
      situations, provided that the contemporary literature does not propose concrete
      guidelines. 

PMID- 24295388
TI  - Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Potential biomarkers to aid diagnosis and therapy need to be
      identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal
      degenerative disorder. The present study was designed to identify the factor(s)
      which are differentially expressed in the cerebrospinal fluid (CSF) of patients
      with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be
      associated with the pathogenesis of this disease. RESULTS: Quantitative mass
      spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients
      undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the
      ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1
      (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT
      1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was
      also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was
      found to be expressed by the Iba-1 immunopositive microglia. CONCLUSION: Elevated
      CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the
      disease pathogenesis. Its synthesis and release from microglia into the CSF may
      be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify
      enhanced microglial activity which may exacerbate the process of
      neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can
      serve as a potential CSF biomarker for the diagnosis of SALS.

PMID- 24295390
TI  - Scalping forehead transposition flap for total eyelid reconstruction with
      periocular involvement associated with a conjunctival cyst formation.
AB  - INTRODUCTION: Total upper and lower eyelid loss due to carcinoma or trauma while
      conserving a functioning eye is rarely seen. In such cases being able to maintain
      the ocular surface may prove to be a surgical challenge, more so when there is a
      history of tumor recurrence, multiple procedures or tissue loss that exceeds the
      palpebral region, thus limiting the reconstructive options. CASE AND TECHNIQUE:
      We present a case report where a scalping forehead transposition flap pedicled on
      the superficial temporal artery territory was performed to reconstruct a full
      thickness skin defect that involved the dorsum of the nose, cheek, upper and
      lower eyelids. A conjunctival advancement flap for ocular surface protection was
      used that unexpectedly rendered a cystic cavity that functioned as a tissue
      expander. COMMENT: Although the technique requires at least two surgical stages,
      we recommend this approach when other options are not feasible.

PMID- 24295389
TI  - Stereoselective 1,3-insertions of rhodium(II) azavinyl carbenes.
AB  - Rhodium(II) azavinyl carbenes, conveniently generated from 1-sulfonyl-1,2,3
      triazoles, undergo a facile, mild, and convergent formal 1,3-insertion into N-H
      and O-H bonds of primary and secondary amides, various alcohols, and carboxylic
      acids to afford a wide range of vicinally bisfunctionalized (Z)-olefins with
      perfect regio- and stereoselectivity. Utilizing the distinctive functionality
      installed through these reactions, a number of subsequent rearrangements and
      cyclizations expand the repertoire of valuable organic building blocks
      constructed by reactions of transition-metal carbene complexes, including alpha
      allenyl ketones and amino-substituted heterocycles. 

PMID- 24295391
TI  - Anthocyanidins, proanthocyanidins, and anthocyanins profiling in wine lees by
      solid-phase extraction-liquid chromatography coupled to electrospray ionization
      tandem mass spectrometry with data-dependent methods.
AB  - A method has been developed to study the content of anthocyanidins,
      proanthocyanidicins, and anthocyanins in wine lees, an abundant byproduct from
      wineries. Detection/quantitation of the target compounds was carried out by a
      hyphenated system consisting of a solid-phase extraction workstation (Prospekt-2
      unit) online coupled to a liquid chromatograph-triple-quadrupole tandem mass
      spectrometer (LC-MS/MS), where standards were used for
      identification/quantitation of both anthocyanidins and proanthocyanidins. Owing
      to the lack of anthocyanins standards, advantages from the use of data-dependent
      methods were taken for their identification and confirmatory analysis.
      Combination of the scanning methods (viz. product-ion, precursor-ion, and neutral
      loss scanning) allowed identifying five different anthocyanins present in wine
      residues. The results thus obtained have been validated by complementary analysis
      of the extracts using LC-TOF/MS in high-resolution mode. Quantitation of the
      monitored compounds was supported on selected reaction monitoring (SRM) and
      calibration curves run with standards of anthocyanidins and proanthocyanidins. 

PMID- 24295396
TI  - Growth of high-density-aligned and semiconducting-enriched single-walled carbon
      nanotubes: decoupling the conflict between density and selectivity.
AB  - Single-walled carbon nanotubes (SWNTs) are highly desired for future electronic
      applications due to the excellent electrical, mechanical, and thermal properties.
      However, the density and the selectivity in the growth of aligned semiconducting
      nanotubes do not coexist previously: when the selectivity is high, the density is
      low and vice versa. In the present work, we found that random carbon nanotubes
      (CNTs) in the catalyst area block the growth of aligned SWNTs along the lattice
      structure on the quartz surface, thus significantly reducing the density of
      nanotubes during growth. More interestingly, it was shown that the random CNTs
      can be selectively removed through appropriate treatments using water vapor as an
      in situ etchant while the aligned SWNTs survive even after long-time water vapor
      treatment. To obtain high-density semiconducting SWNT arrays, we designed an
      improved multiple-cycle growth method, which included the treatment of SWNTs with
      water vapor after each growth cycle without cooling the system. Using this
      method, we have successfully obtained dense semiconducting SWNTs (~10 SWNTs/MUm)
      over large areas and with high uniformity. 

PMID- 24295398
TI  - Comparison of unimolecular decomposition pathways for carboxylic acids of
      relevance to biofuels.
AB  - Quantum mechanical molecular modeling is used [M06-2X/6-311++G(2df,p)] to compare
      activation energies and rate constants for unimolecular decomposition pathways of
      saturated and unsaturated carboxylic acids that are important in the production
      of biofuels and that are models for plant and algae-derived intermediates.
      Dehydration and decarboxylation reactions are considered. The barrier heights to
      decarboxylation and dehydration are similar in magnitude for saturated acids (~71
      kcal mol(-1)), with an approximate 1:1 [H2O]/[CO2] branching ratio over the
      temperature range studied (500-2000 K). alpha,beta-Unsaturation lowers the
      barrier to decarboxylation between 2.2 and 12.2 kcal mol(-1) while increasing the
      barriers to dehydration by ~3 kcal mol(-1). The branching ratio, as a result, is
      an order of magnitude smaller, [H2O]/[CO2] = 0.07. For some alpha,beta
      unsaturated acids, six-center transition states are available for dehydration,
      with barrier heights of ~35.0 kcal mol(-1). The branching ratio for these acids
      can be as high as 370:1. beta,gamma-Unsaturation results in a small lowering in
      the barrier height to decarboxylation (~70.0 kcal mol(-1)). beta,gamma
      Unsaturation also leads to a lowering in the dehydration pathway from 1.7 to 5.1
      kcal mol(-1). These results are discussed with respect to predicted kinetic
      values for acids of importance in biofuels production. 

PMID- 24295397
TI  - A cluster-randomized controlled trial to study the effectiveness of a protocol
      based lifestyle program to prevent type 2 diabetes in people with impaired
      fasting glucose.
AB  - BACKGROUND: Effective diabetes prevention strategies that can be implemented in
      daily practice, without huge amounts of money and a lot of personnel are needed.
      The Dutch Diabetes Federation developed a protocol for coaching people with
      impaired fasting glucose (IFG; according to WHO criteria: 6.1 to 6.9 mmol/l) to a
      sustainable healthy lifestyle change: 'the road map towards diabetes prevention'
      (abbreviated: Road Map: RM). This protocol is applied within a primary health
      care setting by a general practitioner and a practice nurse. The feasibility and
      (cost-) effectiveness of care provided according to the RM protocol will be
      evaluated. METHODS/DESIGN: A cluster randomised clinical trial is performed, with
      randomisation at the level of the general practices. Both opportunistic screening
      and active case finding took place among clients with high risk factors for
      diabetes. After IFG is diagnosed, motivated people in the intervention practices
      receive 3-4 consultations by the practice nurse within one year. During these
      consultations they are coached to increase the level of physical activity and
      healthy dietary habits. If necessary, participants are referred to a dietician,
      physiotherapist, lifestyle programs and/or local sports activities. The control
      group receives care as usual. The primary outcome measure in this study is change
      in Body Mass Index (BMI). Secondary outcome measures are waist circumference,
      physical activity, total and saturated fat intake, systolic blood pressure, blood
      glucose, total cholesterol, HDL cholesterol, triglycerides and behaviour
      determinants like risk perception, perceived knowledge and motivation. Based on a
      sample size calculation 120 people in each group are needed. Measurements are
      performed at baseline, and after one (post-intervention) and two years follow up.
      Anthropometrics and biochemical parameters are assessed in the practices and
      physical activity, food intake and their determinants by a validated
      questionnaire. The cost-effectiveness is estimated by using the Chronic Disease
      Model (CDM). Feasibility will be tested by interviews among health care
      professionals. DISCUSSION: The results of the study will provide valuable
      information for both health care professionals and policy makers. If this study
      shows the RM to be both effective and cost-effective the protocol can be
      implemented on a large scale. TRIAL REGISTRATION: ISRCTN41209683. Ethical
      approval number: NL31342.075.10.

PMID- 24295400
TI  - News report on the 10th annual IAVE meeting in Chicago, IL, USA.

PMID- 24295399
TI  - Transabdominal ultrasonography of the ruminal mucosa as a tool to diagnose
      subacute ruminal acidosis in adult dairy bulls: a pilot study.
AB  - Subacute rumen acidosis (SARA) is frequently encountered in ruminants on high
      concentrate rations and characterized by mild to moderate rumen pH depression.
      Although the measurement of rumen pH is considered as a gold standard approach to
      diagnose SARA, rumen fluid collection is conceived as a cumbersome and invasive
      procedure. In the present study, the suitability of transabdominal
      ultrasonography to identify structural changes of the rumen mucosa associated
      with SARA was explored. Five adult rumen canulated bulls previously adjusted to a
      roughage-based ration were switched in 10-day intervals to rations with
      increasing concentrate content. Seven rations with a concentrate content ranging
      from 5% to 95% were fed. The rumen pH and rumen mucosal thickness were measured
      at the end of each 10-d feeding period. The left flank was divided into 12
      acoustic windows and the mean rumen mucosal thickness for each acoustic window
      determined for each ration. Repeated measure ANOVA and stepwise regression
      analyses were conducted. Increasing the dietary concentrate content resulted in
      thickening of rumen mucosa which was most pronounced in the upper part of the
      ventral rumen sac and the least pronounced in the uppermost and lowermost parts
      of the rumen. The intersection of a horizontal line going through the
      costochondral junction and a vertical line coming from the third lumbar vertebra
      was found to be most suitable to identify animals with rumen pH < 5.5 at 4 h post
      feeding. We conclude that transabdominal ultrasonography of the rumen mucosa has
      the potential to be a suitable, non-invasive diagnostic tool to identify adult
      ruminants with SARA. 

PMID- 24295401
TI  - Accurate label-free protein quantitation with high- and low-resolution mass
      spectrometers.
AB  - Label-free quantitation of proteins analyzed by tandem mass spectrometry uses
      either integrated peak intensity from the parent-ion mass analysis (MS1) or
      features from fragment-ion analysis (MS2), such as spectral counts or summed
      fragment-ion intensity. We directly compared MS1 and MS2 quantitation by
      analyzing human protein standards diluted into Escherichia coli extracts on an
      Orbitrap mass spectrometer. We found that summed MS2 intensities were nearly as
      accurate as integrated MS1 intensities, and both outperformed MS2 spectral
      counting in accuracy and linearity. We compared these results to those obtained
      from two low-resolution ion-trap mass spectrometers; summed MS2 intensities from
      LTQ and LTQ Velos instruments were similar in accuracy to those from the
      Orbitrap. Data from all three instruments are available via ProteomeXchange with
      identifier PXD000602. Abundance measurements using MS1 or MS2 intensities had
      limitations, however. While measured protein concentration was on average well
      correlated with the known concentration, there was considerable protein-to
      protein variation. Moreover, not all human proteins diluted to a mole fraction of
      10(-3) or lower were detected, with a strong falloff below 10(-4) mole fraction.
      These results show that MS1 and MS2 intensities are simple measures of protein
      abundance that are on average accurate but should be limited to quantitation of
      proteins of intermediate to higher fractional abundance. 

PMID- 24295402
TI  - Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model
      of pulmonary emphysema.
AB  - The aim of this study was to characterize the evolution of lung function and 
      structure in elastase-induced emphysema in adult mice and the effect of
      mesenchymal stromal cell (MSC) administration on these parameters. Adult mice
      were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce
      emphysema. MSCs were administered intratracheally or intravenously, before or
      after elastase injection. Lung function measurements, histological and
      morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months
      after elastase and at 19, 20 and 21 days following MSC administration. Elastase
      treated mice showed increased dynamic compliance and total lung capacity, and
      reduced tissue-specific elastance and forced expiratory flows at 3 weeks after
      elastase, which persisted during 10 months follow-up. Histology showed
      heterogeneous alveolar destruction which also persisted during long-term follow
      up. Jugular vein injection of MSCs before elastase inhibited deterioration of
      lung function but had no effects on histology. Intratracheal MSC treatment did
      not modify lung function or histology. In conclusion, elastase-treated mice
      displayed persistent characteristics of pulmonary emphysema. Jugular vein
      injection of MSCs prior to elastase reduced deterioration of lung function.
      Intratracheal MSC treatment had no effect on lung function or histology.

PMID- 24295403
TI  - Effect of tocilizumab on haematological markers implicates interleukin-6
      signalling in the anaemia of rheumatoid arthritis.
AB  - INTRODUCTION: Our objective was to determine the interrelationships of
      interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants
      and iron metabolism markers (including hepcidin) in patients with rheumatoid
      arthritis (RA). METHODS: Data of patients receiving tocilizumab or placebo in the
      MEASURE study were analysed. We investigated associations at baseline and during
      tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron
      homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin,
      haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise
      in haemoglobin level. RESULTS: At baseline, CRP and haptoglobin were inversely
      correlated (modestly) with haemoglobin levels. After treatment with tocilizumab,
      CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC
      and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2
      weeks correlated with a week 12 rise in TIBC and haemoglobin. CONCLUSIONS:
      Inflammatory anaemia improves in patients with RA treated with tocilizumab. This
      improvement correlates with the degree of suppression of systemic inflammation,
      reduction in hepcidin and haptoglobin and increase in iron-binding capacity.
      These clinical data provide evidence of a role for IL-6 signalling in the
      inflammatory anaemia of RA.

PMID- 24295404
TI  - Study of TLR4 and IL-8 gene polymorphisms in H.pylori-induced inflammation in
      gastric cancer in an ethnic Kashmiri population.
AB  - BACKGROUND: TLRs play an essential role in the initial handling of H. pylori and
      determine the clinical outcomes that range from simple asymptomatic gastritis to
      peptic ulcer disease and gastric cancer. Asp299Gly and Thr399Ile polymorphisms in
      TLR4 have been associated with a variety of inflammatory and infectious
      conditions including gastric cancer. The T-251A polymorphism in the promoter
      region of IL-8 gene has been found to be associated with changing the in vitro
      levels of IL-8 production. IL-8 exhibits angiogenic activity and is responsible
      for tumor-associated angiogenesis in several cancers. MATERIALS AND METHODS: 130
      gastric cancer patients and 200 healthy controls were included in this study. DNA
      extraction was followed by PCR detection of H. pylori infection, PCR-RFLP for the
      TLR 4 polymorphism and PCR-CTPP for IL-8 gene polymorphism. RESULTS: The adjusted
      OR for gastric cancer risk was 1.15 (95% CI, 0.8357-1.3463); 1.39 (0.6964-2.781)
      and 1.43 (0.954-2.1515) for Asp299Gly, Thr399Ile and IL-8 T_251A respectively.
      Odds Ratio analysis showed CT genotype and AT and AA genotypes as risk factors
      for the development of gastric cancer. We found the Asp299Gly polymorphism
      carrier to be significantly associated (p value 0.03)with the development of
      tumours in the distal part of the stomach and Thr399Ile polymorphism to be
      significantly associated(p value 0.008) with the development of well
      differentiated gastric adenocarcinoma.The IL-8 T-251A polymorphism was not found
      to be associated with any of the clinicopathological characteristics. DISCUSSION:
      No correlation was found between the appearance of disease and HP infection or
      the presence of TLR4 and IL-8 gene polymorphisms and HP infection.

PMID- 24295405
TI  - Recent progress in the chemotherapy of human fungal diseases. Emphasis on 1,3
      beta-glucan synthase and chitin synthase inhibitors.
AB  - Systemic fungal infections of humans and economically important animals are
      increasingly common throughout the world. These infections are severe and often
      hard to treat with existing safe, oral medications. Thus there has been
      increasing research on alternatives resulting in study of natural and synthetic
      inhibitors of 1,3-beta-Glucan synthase (GS) and chitin synthase (CS)-enzymes
      important in the biosynthesis of fungal cell walls that are not utilized in human
      biochemistry. Some such agents have recently been introduced into parenteral
      clinical use. There is hope that safe agents of this type with oral activity may
      yet emerge. This active area of research and its historic context with
      alternative agents is reviewed herein. 

PMID- 24295406
TI  - Effect of pendant group on pDNA delivery by cationic-beta-cyclodextrin:alkyl-PVA
      PEG pendant polymer complexes.
AB  - We have previously shown that cationic-beta-cyclodextrin:R-poly(vinyl alcohol)
      poly(ethylene glycol) (CD+:R-PVA-PEG) pendant polymer host:guest complexes are
      safe and efficient vehicles for nucleic acid delivery, where R = benzylidene
      linked adamantyl or cholesteryl esters. Herein, we report the synthesis and
      biological performance of a family of PVA-PEG pendant polymers whose pendant
      groups have a wide range of different affinities for the beta-CD cavity.
      Cytotoxicity studies revealed that all of the cationic-beta-CD:pendant polymer
      host:guest complexes have 100-1000-fold lower toxicity than branched
      polyethylenimine (bPEI), with pDNA transfection efficiencies that are comparable
      to bPEI and Lipofectamine 2000. Complexes formed with pDNA at N/P ratios greater
      than 5 produced particles with diameters in the 100-170 nm range and zeta
      potentials of 15-35 mV. Gel shift and heparin challenge experiments showed that
      the complexes are most stable at N/P >= 10, with adamantyl- and noradamantyl
      modified complexes displaying the best resistance toward heparin-induced
      decomplexation. Disassembly rates of fluoresceinated-pDNA:CD(+):R-PVA-PEG
      rhodamine complexes within HeLa cells showed a modest dependence on host:guest
      binding constant, with adamantyl-, noradamantyl-, and dodecyl-based complexes
      showing the highest loss in FRET efficiency 9 h after cellular exposure. These
      findings suggest that the host:guest binding constant has a significant impact on
      the colloidal stability in the presence of serum and cellular uptake efficiency,
      whereas endosomal disassembly and transfection performance of cationic-beta-CD:R
      poly(vinyl alcohol)-poly(ethylene glycol) pendant polymer complexes appears to be
      controlled by the hydrolysis rates of the acetal grafts onto the PVA main chain. 

PMID- 24295409
TI  - Incidence and prognostic value of recurrent chromosomal abnormalities in elderly
      patients with multiple myeloma.
AB  - Chromosomal abnormalities are well-established biomarkers used in the
      subclassification and risk stratification of multiple myeloma patients. Patients
      with t(4;14)(p16;q32) and deletion 17p13 are considered to have a poor prognosis,
      and do not respond to any of the available therapies. However, most studies of
      chromosomal abnormalities incidence and risk stratification have been performed
      in patients younger than 66 years of age; therefore we have very limited data on
      the elderly population. This study was designed to uncover the incidence and
      clinical significance of 17p13 and 13q14 deletions and t(4;14) in a large cohort
      of clinically annotated multiple myeloma patients older than 66 years of age.
      Interestingly, the incidence of deletion of 13q14 and t(4;14) decreased with age,
      being significantly lower in patients >75 years old than in patients <75 years
      old. Conversely, the incidence of deletion 17p13 was not different between
      groups. Importantly, this study confirmed that t(4;14) and deletion 17p13
      maintain a poor prognosis value in the elderly (66-75 years old) and the very
      elderly population (>75 years old), regardless of the treatment received.

PMID- 24295410
TI  - Sunitinib in malignant melanoma: a treatment option only for KIT-mutated
      patients?
AB  - Sunitinib has previously been reported to be potentially effective in the
      treatment of malignant melanomas expressing c-KIT. Here we report on the case of
      a 77-year-old gentleman affected by a metastatic clear cell carcinoma of the
      kidney and a metastatic malignant melanoma with liver and lung metastases.
      Despite the negativity for CD117 and the absence of KIT amplification or
      mutations in the melanoma specimen, he achieved a partial response both in the
      lungs and in the liver while on sunitinib (50 mg once/day, 4 weeks on/2 weeks
      off) for the treatment of kidney cancer. To our knowledge, this represents the
      first evidence of sunitinib activity in KIT wild-type melanoma. Further studies
      should be performed to confirm these preliminary data.

PMID- 24295407
TI  - The role of bacterial protein tyrosine phosphatases in the regulation of the
      biosynthesis of secreted polysaccharides.
AB  - SIGNIFICANCE: Tyrosine phosphorylation and associated protein tyrosine
      phosphatases are gaining prominence as critical mechanisms in the regulation of
      fundamental processes in a wide variety of bacteria. In particular, these
      phosphatases have been associated with the control of the biosynthesis of
      capsular polysaccharides and extracellular polysaccharides, critically important
      virulence factors for bacteria. RECENT ADVANCES: Deletion and overexpression of
      the phosphatases result in altered polysaccharide biosynthesis in a range of
      bacteria. The recent structures of associated auto-phosphorylating tyrosine
      kinases have suggested that the phosphatases may be critical for the cycling of
      the kinases between monomers and higher order oligomers. CRITICAL ISSUES:
      Additional substrates of the phosphatases apart from cognate kinases are
      currently being identified. These are likely to be critical to our understanding
      of the mechanism by which polysaccharide biosynthesis is regulated. FUTURE
      DIRECTIONS: Ultimately, these protein tyrosine phosphatases are an attractive
      target for the development of novel antimicrobials. This is particularly the case
      for the polymerase and histidinol phosphatase family, which is predominantly
      found in bacteria. Furthermore, the determination of bacterial tyrosine
      phosphoproteomes will likely help to uncover the fundamental roles, mechanism,
      and critical importance of these phosphatases in a wide range of bacteria.

PMID- 24295411
TI  - Excellent response to combined radioiodine and enoxaparin in the setting of tumor
      venous thrombosis from differentiated thyroid carcinoma involving internal
      jugular and subclavian veins.
AB  - A striking clinical, radiological and tumor marker response obtained with a
      combined approach of radioiodine (I-131; single fraction) coupled with
      subcutaneous enoxaparin (a low-molecular-weight heparin) in the setting of
      differentiated thyroid carcinoma with jugular vein tumor thrombosis and
      metastatic pulmonary disease is described in this article. Pulmonary metastases,
      a frequent accompaniment in this group of patients, also demonstrated remarkable
      response with a single fraction of I-131. The proposed approach of combining
      targeted I-131 therapy with the antithrombotic effect of low-molecular-weight
      heparin in patients with thyroid cancer with documented tumor venous thrombosis
      is likely to produce a synergistic effect, with a dramatic clinical response that
      requires a minimal I-131 dose. The noninvasive nature and ease of the approach,
      which has an impressive response and findings, calls for administering this
      therapeutic option more in such patients in the future. This could lead to the
      development of an effective treatment strategy in these patients based upon
      generated evidence.

PMID- 24295412
TI  - Romidepsin for cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphomas are relatively rare lymphomas and the most common form
      is mycosis fungoides. Its rare leukemic variant is Sezary syndrome. Advanced
      stage disease is typically treated with bexarotene (a retinoid), IFN-alpha or
      conventional chemotherapeutic agents, but relapses are inevitable. Histone
      deacetylase inhibitors that modify the epigenome are an attractive addition to
      the armamentarium. Based on two large Phase II studies, the US FDA approved
      intravenous romidepsin for patients with relapsed/refractory cutaneous T-cell
      lymphomas. Romidepsin provides a subset of patients with an opportunity for
      prolonged clinical responses with a tolerable side-effect profile.

PMID- 24295413
TI  - Ofatumumab: a novel, fully human anti-CD20 monoclonal antibody for the treatment
      of chronic lymphocytic leukemia.
AB  - Ofatumumab is a fully human, IgG anti-CD20 monoclonal antibody codeveloped by
      GlaxoSmithKline (Brentford, UK) and Genmab (Copenhagen, Denmark). In preclinical
      studies, ofatumumab exhibited more potent in vitro activity than rituximab
      against B-cell malignancies and prolonged survival in in vivo animal models
      compared with rituximab. Ofatumumab is clinically well tolerated with initial
      infusion reactions being the predominant associated toxicity. Ofatumumab has
      demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia (CLL)
      and has received regulatory approval in both Europe and the USA for treatment of
      fludarabine and alemtuzumab refractory disease. Single-agent ofatumumab has
      resulted in overall response rates of 42-51% in relapsed/refractory CLL and up to
      80% when combined with chemotherapy. In de novo CLL, overall response rates of 77
      78% have been achieved.

PMID- 24295414
TI  - Eribulin in cutaneous breast cancer metastasis treatment: clinical activity and
      symptom control.
AB  - AIM: This observational study evaluated the behavior and outcome of cutaneous
      breast cancer metastasis treated with eribulin. PATIENTS & METHODS: From November
      2012 to January 2013, oncologists completed a database with patient, tumor and
      treatment characteristics from 14 Italian cancer centers. Skin lesions were
      assessed by Response Evaluation Criteria In Solid Tumors and cutaneous symptoms
      by present/absent criteria. RESULTS: A total of 23 metastatic breast cancer
      patients with skin metastasis who were treated with eribulin were analyzed. After
      treatment, 43% of patients exhibited a partial response, 35% stable disease and
      22% progressive disease. Regarding only the skin response, 26% obtained a
      complete response, 22% a partial response, 39% stable disease and 13% progressive
      disease. We found an improvement in symptoms, infiltration and ulceration. With a
      median follow-up of 6 months, median progression-free survival was 4.3 months and
      median overall survival was 9.1 months. CONCLUSION: The response rate of skin
      metastasis to eribulin treatment was coherent with systemic responses. The good
      clinical response in most patients reflected symptom improvement.

PMID- 24295415
TI  - Liposomal chemotherapeutics.
AB  - Currently, six liposomal chemotherapeutics have received clinical approval and
      many more are in clinical trials or undergoing preclinical evaluation. Liposomes
      exhibit low toxicity and improve the biopharmaceutical features and therapeutic
      index of drugs, thereby increasing efficacy and reducing side effects. In this
      review we discuss the advantages of using liposomes for the delivery of
      chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to
      illustrate how the performance of a metabolically unstable or poorly water
      soluble drug can be greatly improved by liposomal incorporation. We look at the
      beneficial effects of liposomes in a variety of solid and blood-borne tumors,
      including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.

PMID- 24295416
TI  - Cell-free DNA for the detection of pancreatic, liver and upper gastrointestinal
      cancers: has progress been made?
AB  - Detecting alterations in blood cell-free DNA (cfDNA) is hoped to be a novel,
      noninvasive method for diagnosing, prognosing and monitoring cancer patients.
      Several studies have assessed the usefulness of measuring tumor-specific genetic
      and epigenetic changes of cfDNA, such as loss of heterozygosity, frequency of
      mutations, alterations of microsatellites and the methylation of genes in patient
      blood samples. However, few well-designed trials have been carried out to
      translate these findings effectively. In this review, we have assessed the
      clinical utility of cfDNA in pancreatic, liver and upper gastrointestinal
      malignancies.

PMID- 24295417
TI  - Breast cancer in the elderly: which lessons have we learned?
AB  - Management of older breast cancer patients is challenging due to a lack of good
      quality evidence regarding the role of adjuvant chemotherapy. Older women can
      benefit as much from adjuvant chemotherapy as younger women, although they have
      an increased risk of toxicities. Decisions regarding adjuvant chemotherapy should
      be made based on tumor biology and biological age, rather than chronological age.
      Geriatrician assessment can detect subtle functional deficits that may impact on
      the ability of the patient to tolerate chemotherapy; however, implementation of
      comprehensive geriatric assessment in the oncology setting is challenging.
      Instead, numerous frailty screening tools are in development. Future advances
      should incorporate more accurate and efficient means for determining the
      biological age of elderly breast cancer patients, which will better define the
      risk:benefit ratio of adjuvant chemotherapy.

PMID- 24295418
TI  - Mammalian target of rapamycin inhibitor-associated stomatitis.
AB  - With the recent introduction of inhibitors of mammalian target of rapamycin
      (mTOR) in oncology, distinct cutaneous and oral adverse events have been
      identified. In fact, stomatitis and rash are documented as the most frequent and
      potentially dose-limiting side effects. Clinically, mTOR inhibitor-associated
      stomatitis (mIAS) more closely resembles aphthous stomatitis than oral mucositis
      due to conventional anticancer therapies. While most cases of mIAS are mild to
      moderate and self-limiting, more severe and persistent mIAS can become a dose
      limiting toxicity. Small ulcerations may cause significant pain and mucosal
      sensitivity may occur in the absence of clinical changes. Use of clinical
      assessment tools that are primarily driven by ulceration size may underestimate
      mIAS, and assessment should include patient-reported outcomes. This article
      provides an up-to-date review of the clinical presentation, terminology,
      pathogenesis, assessment and management of mIAS and other mTOR inhibitor
      associated oral adverse events. In addition, areas of future research are
      considered.

PMID- 24295419
TI  - Recent advances in oral anticancer agents for colon cancer.
AB  - To provide therapeutic alternatives to intravenous colon chemotherapy major
      recent research is focusing on the development of oral chemotherapeutic agents
      with the intention to improve the quality of life of patients. Initially 5
      fluorouracil was most commonly used for the treatment of colorectal cancer but
      currently oxaliplatin and irinotecan are also available. The majority of these
      new drugs are pyrimidines and their analogs. The rationale for using oral
      anticancer agents is discussed and new drugs, such as farnesyl protein
      transferase inhibitor S-1, rubitecan, ZD9331, MMI-166, eflornithine, sulindac,
      and oral camptothecin analogs, among others, are presented with the results of
      their preclinical and clinical developments. This article focuses on the
      advancement of clinical development and also discusses the relative merits and
      demerits of these agents. The accelerated approval of these agents by regulatory
      authorities is supported by survival benefit, response rate and time to
      progression.

PMID- 24295420
TI  - Prognostic and predictive markers for personalized adjuvant therapy for non-small
      cell lung cancer patients.
AB  - Adjuvant chemotherapy following surgical resection in non-small-cell lung cancer
      patients with large tumors (>4 cm) or tumors with lymph node metastases has
      emerged as a standard of care. The benefits of adjuvant chemotherapy are modest,
      with a 5-year survival improvement of only 5-10%. In addition, survival rates of
      25% or greater with surgery alone suggest that some patients do not need adjuvant
      therapy. Therefore, there is a need to develop prognostic and predictive markers
      to identify patients in need of adjuvant therapy and the patients likely to
      benefit from such therapy. Many factors have been evaluated for this purpose and
      some of these factors, such as visceral pleural invasion, can influence the
      decision to use adjuvant chemotherapy. However, most of the available data are
      retrospective, which limits the utility of these markers in current practice.
      Ongoing trials are evaluating many promising markers and may guide adjuvant
      therapy in the future.

PMID- 24295421
TI  - IDH mutations in tumorigenesis and their potential role as novel therapeutic
      targets.
AB  - Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of
      isocitrate to alpha-ketoglutarate (alpha-KG). Somatic mutations in genes encoding
      IDH1 and IDH2 were first identified in glioma and subsequently in acute myeloid
      leukemia and other solid tumors. These heterozygous point mutations occur at the
      arginine residue of the enzyme's active site and cause both loss of normal enzyme
      function and gain of function, causing reduction of alpha-KG to D-2
      hydroxyglutarate, which accumulates. D-2-hydroxyglutarate may act as an
      oncometabolite through the inhibition of various alpha-KG-dependent enzymes,
      stimulating angiogenesis, histone modifications and aberrant DNA methylation.
      Possibly, IDH mutations may also cause oncogenic effects through dysregulation of
      the tricarboxylic acid cycle, or by increasing susceptibility to oxidative
      stress. Clinically, IDH mutations may be useful diagnostic, prognostic and
      predictive biomarkers, and it is anticipated that a better understanding of the
      pathogenesis of IDH mutations will enable IDH-directed therapies to be developed
      in the future.

PMID- 24295423
TI  - Topological aspects of charge-carrier transmission across grain boundaries in
      graphene.
AB  - Dislocations and grain boundaries are intrinsic topological defects of large
      scale polycrystalline samples of graphene. These structural irregularities have
      been shown to strongly affect electronic transport in this material. Here, we
      report a systematic investigation of the transmission of charge carriers across
      the grain-boundary defects in polycrystalline graphene by means of the Landauer
      Buttiker formalism within the tight-binding approximation. Calculations reveal a
      strong suppression of transmission at low energies upon decreasing the density of
      dislocations with the smallest Burgers vector b = (1,0). The observed transport
      anomaly is explained from the point of view of resonant backscattering due to
      localized states of topological origin. These states are related to the gauge
      field associated with all dislocations characterized by b = (n,m) with n - m ? 3q
      (q ? Z). Our work identifies an important source of charge-carrier scattering
      caused by the topological defects present in large-area graphene samples produced
      by chemical vapor deposition.

PMID- 24295424
TI  - Executive functioning in obstructive sleep apnea syndrome patients without
      comorbidities: focus on the fractionation of executive functions.
AB  - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is associated with impaired
      cognition, especially executive functions. However, various of its comorbid
      conditions are also known to cause cognitive impairment, so it is unclear whether
      OSAS itself is responsible for cognitive deficits. Our aim was to determine the
      effects of OSAS on executive functions in otherwise healthy patients. METHOD:
      This was a parallel group design study, which involved 22 patients aged 36-65
      years diagnosed with moderate to severe OSAS, whose body mass index was below 26,
      and who did not have diabetes, hypertension, or depression. Controls were 22
      healthy individuals with similar age, gender, intelligence quotient, and
      schooling to those of the patients. Participants completed a test battery that
      included measures of 6 distinct executive domains (shifting, inhibition,
      updating, dual-task performance, planning, and access to long-term memory), of
      all subsystems of the multiple-component working memory model, attention, and
      mood. RESULTS: OSAS and controls were equivalent in all demographic variables and
      test scores. The apnea-hypopnea index did not significantly correlate with
      executive performance, but mean oxygen saturation did so with measurements of
      executive shifting and access to long-term memory. CONCLUSIONS: OSAS without
      comorbidities did not lead to cognitive impairment.

PMID- 24295426
TI  - Qualitative evaluation of mental health services for clients with limited English
      proficiency.
AB  - BACKGROUND: To meet federal requirements under Title VI of the Civil Rights Act,
      the state of California instituted policies requiring that comprehensive mental
      health services in native languages be made available to limited English
      proficiency (LEP) populations when concentrations exceed "threshold" levels.
      METHODS: This paper builds on promising results from quantitative evaluations by
      reporting on qualitative interviews with Latino and Vietnamese LEP clients in
      mental health services (N = 20) to examine the awareness, impact, and
      implications of these threshold language policies. RESULTS: Results suggest that,
      while individuals are often not aware of the policies themselves, the language
      related services they receive that are prompted by the policies are critical to
      treatment initiation and retention. Results also convey the complexities of using
      interpreters for sensitive psychological topics, and suggest that, for LEP
      individuals seeking mental health treatment, providers who speak their native
      languages are generally preferred. CONCLUSIONS: Access to language-appropriate
      services seems to be an important part of why LEP populations seek mental health
      treatment. However, there are multiple variables that factor into the usage and
      usefulness of such services.

PMID- 24295428
TI  - Effects of stimulus order on discrimination processes in comparative and equality
      judgements: data and models.
AB  - In typical discrimination experiments, participants are presented with a constant
      standard and a variable comparison stimulus and their task is to judge which of
      these two stimuli is larger (comparative judgement). In these experiments,
      discrimination sensitivity depends on the temporal order of these stimuli (Type B
      effect) and is usually higher when the standard precedes rather than follows the
      comparison. Here, we outline how two models of stimulus discrimination can
      account for the Type B effect, namely the weighted difference model (or basic
      Sensation Weighting model) and the Internal Reference Model. For both models, the
      predicted psychometric functions for comparative judgements as well as for
      equality judgements, in which participants indicate whether they perceived the
      two stimuli to be equal or not equal, are derived and it is shown that the models
      also predict a Type B effect for equality judgements. In the empirical part, the
      models' predictions are evaluated. To this end, participants performed a duration
      discrimination task with comparative judgements and with equality judgements. In
      line with the models' predictions, a Type B effect was observed for both
      judgement types. In addition, a time-order error, as indicated by shifts of the
      psychometric functions, and differences in response times were observed only for
      the equality judgement. Since both models entail distinct additional predictions,
      it seems worthwhile for future research to unite the two models into one
      conceptual framework. 

PMID- 24295427
TI  - Cation control of diastereoselectivity in iridium-catalyzed allylic
      substitutions. Formation of enantioenriched tertiary alcohols and thioethers by
      allylation of 5H-oxazol-4-ones and 5H-thiazol-4-ones.
AB  - We report highly diastereo- and enantioselective allylations of substituted 5H
      oxazol-4-ones and 5H-thiazol-4-ones catalyzed by a metallacyclic iridium complex.
      Enantioselective Ir-catalyzed allylation of substituted 5H-oxazol-4-ones occurs
      with high diastereoselectivity by employing the corresponding zinc enolates;
      enantioselective Ir-catalyzed allylation of substituted 5H-thiazol-4-ones occurs
      with the corresponding magnesium enolates with high diastereoselectivity. The
      allylation of substituted 5H-oxazol-4-ones provides rapid access to
      enantioenriched tertiary alpha-hydroxy acid derivatives unavailable through Mo
      catalyzed allylic substitution. The allylation of substituted 5H-thiazol-4-ones
      provides a novel method to synthesize enantioenriched tertiary thiols and
      thioethers. The observed cation effect implies a novel method to control the
      diastereoselectivity in Ir-catalyzed allylic substitution. 

PMID- 24295429
TI  - Electrospinning of polyhydroxyalkanoate fibrous scaffolds: effects on
      electrospinning parameters on structure and properties.
AB  - In this study, electrospinning was used to prepare ultrafine fibers from PHAs
      with different chemical compositions: P(3HB) and copolymers: P(3HB-co-4HB), P(3HB
      co-3HV), and P(3HB-co-3HHx). The main process parameters that influence ultrafine
      fiber diameter and properties (polymer concentration, solution feeding rate,
      working distance, and applied voltage) have been investigated and their effects
      evaluated. The study revealed electrospinning parameters for the production of
      high-quality ultrafine fibers and determined which parameters should be varied to
      tailor the properties of the products. This study is the first to compare
      biological and physical-mechanical parameters of PHAs with different chemical
      compositions as dependent upon the fractions of monomers constituting the
      polymers and ultrafine fiber orientation. Mechanical strength of aligned
      ultrafine fibers prepared from different PHAs is higher than that of randomly
      oriented ones; no significant effect of ultrafine fiber orientation on surface
      properties has been found. None of the fibrous scaffolds produced by
      electrospinning from PHAs had any adverse effects on attachment, growth, and
      viability of NIH 3T3 mouse fibroblast cells, and all of them were found to be
      suitable for tissue engineering applications.

PMID- 24295430
TI  - A new case of idiopathic recurrent acute pericarditis due to R104Q mutation in
      TNFRSF1A successfully treated with anakinra: expanding the questions.

PMID- 24295431
TI  - Micellar catalysis using a photochromic surfactant: application to the Pd
      catalyzed Tsuji-Trost reaction in water.
AB  - The first example of a Pd-catalyzed Tsuji-Trost reaction, applied in a
      photochromic micellar media under conventional heating and microwave irradiation,
      is reported. The surfactant activity and recycling ability were investigated and
      compared with those of a few commercially available surfactants. The synthetic
      photochromic surfactant proved to be efficient, recyclable, and versatile for Pd
      catalyzed coupling reactions. 

PMID- 24295432
TI  - Vascular alterations in the sprague-dawley rat mandible during intravenous
      bisphosphonate therapy.
AB  - Long-term use of intravenous bisphosphonates, such as zoledronic acid
      (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw
      (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most
      cases. To determine the effects of zoledronic acid on the vascular structure of
      the rat mandible. Extracted of the mandibular first molar in rats that received 2
      IV injections of zoledronate (20 MUg/kg), 4 weeks apart. Zoledronate-treated rats
      (n = 18) were then compared to a control group of untreated rats (n = 18). At the
      fourth, eighth, and 12th week after molar extraction, 8 rat mandibles from each
      group were perfused with 35% radiopaque triphenylbismuth in methyl methacrylate
      via carotid artery perfusion. Mandibles were harvested and examined by micro-CT
      to assess the spatial and dimensional changes of the vasculature as a result of
      zoledronate treatment. The micro-CT analysis showed that zoledronic acid-treated
      rats had blood vessels that were thicker, less connected, and less ordered than
      control rats that were not exposed to zoledronic acid. This study demonstrated
      that treatment with zoledronic acid in rats is associated with vascular changes
      in alveolar bone. Further studies are underway to explore whether these vascular
      changes contribute to the pathogenesis of BRONJ. 

PMID- 24295433
TI  - The evaluation of the reactivating and therapeutic efficacy of two novel oximes
      (K361 and K378) in comparison with the oxime K203 and trimedoxime in tabun
      poisoned rats and mice.
AB  - The potency of two newly developed oximes (K361 and K378) to reactivate tabun
      inhibited cholinesterase and to reduce acute toxicity of tabun was compared with
      the oxime K203 and trimedoxime using in vivo methods. The study determining
      percentage of reactivation of tabun-inhibited diaphragm cholinesterase in
      poisoned rats showed that the reactivating efficacy of the oxime K378 is slightly
      lower than the reactivating potency of the oxime K203 and trimedoxime while the
      ability of the oxime K361 to reactivate tabun-inhibited cholinesterase is
      markedly lower compared with the oxime K203 and trimedoxime. In the brain, the
      potency of both newly developed oximes to reactivate tabun-inhibited
      cholinesterase was negligible. The therapeutic efficacy of both newly developed
      oximes roughly corresponds to their weak reactivating efficacy. Their potency to
      reduce acute toxicity of tabun was significantly lower compared with the oxime
      K203 as well as trimedoxime. In conclusion, the reactivating and therapeutic
      potency of both newly developed oximes does not prevail the effectiveness of the
      oxime K203 and trimedoxime and, therefore, they are not suitable for their
      replacement of commonly used oximes for the treatment of acute tabun poisoning.

PMID- 24295434
TI  - Ultrathin Pt-Cu nanosheets and nanocones.
AB  - In this work, we have successfully synthesized free-standing ultrathin Pt-Cu
      alloy nanosheets of 4-6 atom thickness with tunable lateral size from 10 to 50
      nm. The nanosheets with diameters >20 nm can be converted into nanocones in a
      controllable way. These nanosheets and nanocones exhibit excellent
      electrocatalytic activities for the oxidation of ethanol in comparison to
      commercial Pt black and Pt/C catalysts. 

PMID- 24295435
TI  - Multi-view fast-ion D-alpha spectroscopy diagnostic at ASDEX Upgrade.
AB  - A novel fast-ion D-alpha (FIDA) diagnostic that is based on charge exchange
      spectroscopy has been installed at ASDEX Upgrade. The diagnostic uses a newly
      developed high-photon-throughput spectrometer together with a low-noise EM-CCD
      camera that allow measurements with 2 ms exposure time. Absolute intensities are
      obtained by calibrating the system with an integrating sphere and the wavelength
      dependence is determined to high accuracy using a neon lamp. Additional
      perturbative contributions to the spectra, such as D2-molecular lines, the Stark
      broadened edge D-alpha emission, and passive FIDA radiation have been identified
      and can be subtracted or avoided experimentally. The FIDA radiation from fast
      deuterium ions after charge exchange reactions can therefore be analyzed
      continuously without superimposed line emissions at large Doppler shifts. Radial
      information on the fast ions is obtained from radially distributed lines of
      sight. The investigation of the fast-ion velocity distribution is possible due to
      three different viewing geometries. The independent viewing geometries access
      distinct parts of the fast-ion velocity space and make tomographic
      reconstructions possible. 

PMID- 24295436
TI  - Spectrally resolved motional Stark effect measurements on ASDEX Upgrade.
AB  - A spectrally resolved Motional Stark Effect (MSE) diagnostic has been installed
      at ASDEX Upgrade. The MSE data have been fitted by a forward model providing
      access to information about the magnetic field in the plasma interior [R. Reimer,
      A. Dinklage, J. Geiger et al., Contrib. Plasma Phys. 50, 731-735 (2010)]. The
      forward model for the beam emission spectra comprises also the fast ion Dalpha
      signal [W. W. Heidbrink and G. J. Sadler, Nucl. Fusion 34, 535-615 (1994)] and
      the smearing on the CCD-chip. The calculated magnetic field data as well as the
      revealed (dia)magnetic effects are consistent with the results from equilibrium
      reconstruction solver. Measurements of the direction of the magnetic field are
      affected by unknown and varying polarization effects in the observation. 

PMID- 24295437
TI  - Random unstimulated pediatric luteinizing hormone levels are not reliable in the
      assessment of pubertal suppression during histrelin implant therapy.
AB  - BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa)-stimulated luteinizing
      hormone (LH) is the standard hormonal assessment for both diagnosis and
      therapeutic monitoring of children with central precocious puberty (CPP). Use of
      unstimulated (random) LH levels may be helpful in diagnosis and has gained
      popularity in monitoring GnRHa therapy despite lack of validation against
      stimulated values. The objective of this investigation was to assess the
      suitability of random LH for monitoring pubertal suppression during GnRHa
      treatment. METHODS: Data from a multi-year, multicenter, open-label trial of
      annual histrelin implants for CPP was used for our analysis. Children meeting
      clinical and hormonal criteria for CPP, either naive to GnRHa therapy or
      previously treated with another GnRHa for at least 6 months who were being
      treated at academic pediatric centers were included in the study. Subjects
      received a single 50-mg subcutaneous histrelin implant annually until final
      explant at an age determined at the discretion of each investigator. Monitoring
      visits for physical examination and GnRHa-stimulation testing were performed at
      regular intervals. The main outcome measure was pubertal suppression during
      treatment defined by peak LH < 4 mIU/mL after GnRHa stimulation. RESULTS: During
      histrelin treatment, 36 children underwent a total of 308 monitoring GnRHa
      stimulation tests. Unstimulated and peak LH levels were positively correlated (r
      = 0.798), and both declined from the first to second year of treatment. Mean +/-
      SD peak LH level during therapy was 0.62 +/- 0.43 mIU/mL (range, 0.06-2.3), well
      below the normal prepubertal mean. Mean random LH was 0.35 +/- 0.25 mIU/mL
      (range, 0.04-1.5), 10-fold higher than the normal prepubertal mean. The random LH
      levels were above the prepubertal upper threshold (<0.3 mIU/mL) in 48.4% of all
      tests and in 88.9% of subjects at some point during therapy. CONCLUSIONS: In
      contrast with GnRHa-stimulated LH, unstimulated LH values frequently fail to
      demonstrate suppression to prepubertal values during GnRHa therapy for CPP,
      despite otherwise apparent pubertal suppression, and are thus unsuitable for
      therapeutic monitoring. TRIAL REGISTRATION: ClinicalTrial.gov NCT00779103.

PMID- 24295438
TI  - Catastrophic growth of gas hydrates in the presence of kinetic hydrate
      inhibitors.
AB  - The effect of the concentration of kinetic hydrate inhibitors,
      polyvinylpyrrolidone (PVP), and polyvinylcaprolactam (PVCap) on the onset and
      growth of synthetic natural gas hydrates is investigated by measuring the hydrate
      onset time and gas consumption rate. Although the hydrate onset time is extended
      by increasing the concentration from 0.5 to 3.0 wt % for both PVP and PVCap, the
      growth rate of hydrates shows that the different tendency depends on the type of
      kinetic hydrate inhibitor and its concentration. For PVCap solution, the hydrate
      growth was slow for more than 1000 min after the onset at the concentration of
      0.5 and 1.5 wt %. However, the growth rate becames almost 8 times faster at the
      concentration of 3.0 wt %, representing the catastrophic growth of hydrate just
      after the hydrate onset. (13)C NMR spectra of hydrates formed at 3.0 wt % of PVP
      and PVCap indicate the existence of both structures I and II. Cage occupancy of
      methane in large cages of structure II decreases significantly when compared to
      that for pure water. These results suggest that increasing the concentration of
      KHI up to 3.0 wt % may induce the earlier appearance of catastrophic hydrate
      growth and the existence of metastable structure I; thus, there needs to be an
      upper limit for using KHI to manage the formation of gas hydrates. 

PMID- 24295439
TI  - Mobile phone text messaging for promoting adherence to anti-tuberculosis
      treatment: a systematic review.
AB  - BACKGROUND: Mobile phone text messaging (SMS) has the potential to promote
      adherence to tuberculosis treatment. This systematic review aims to synthesize
      current evidence on the effectiveness of SMS interventions in improving patients'
      adherence to tuberculosis treatment. METHODS: We searched electronic databases
      (PubMed, EMBASE, Science Citation Index), reference lists of relevant articles,
      conference proceedings, and selected websites for eligible studies available by
      15 February 2013; regardless of language or publication status. Two authors
      independently screened selected eligible studies, and assessed risk of bias in
      included studies; resolving discrepancies by discussion and consensus. RESULTS:
      We identified four studies that compared the outcomes of the SMS intervention
      group with controls. Only one of the four studies was a randomized controlled
      trial. This was conducted in Argentina and the SMS intervention did not
      significantly improve adherence to tuberculosis treatment compared to self
      administration of tuberculosis treatment (risk ratio [RR] 1.49, 95% confidence
      intervals [CI] 0.90 to 2.42). One of the non-randomized studies, conducted in
      South Africa, which compared SMS reminders to directly observed therapy short
      course (DOTS) reported similar rates of tuberculosis cure (62.35% vs. 66.4%) and
      treatment success (72.94% vs. 69.4%). A second study from South Africa, utilized
      SMS reminders when patients delayed in opening their pill bottles and reported
      increased tuberculosis cure (RR 2.32, 95% CI 1.60 to 3.36) and smear conversion
      (RR 1.62, 95% CI 1.09 to 2.42) rates compared to DOTS. In the third non
      randomized study, conducted in Kenya, use of SMS reminders increased rates of
      clinic attendance on scheduled days compared to standard care (RR 1.56, 95% CI
      1.06 to 2.29). Using the GRADE approach, we rate the quality of the evidence as
      low, mainly because of the high risk of bias and heterogeneity of effects across
      studies. CONCLUSIONS: This systematic review indicates that there is a paucity of
      high-quality data on the effectiveness of SMS interventions for improving
      patients' adherence to tuberculosis treatment. The low quality of the current
      evidence implies that further studies (in particular randomized trials) on the
      subject are needed. In the interim, if the intervention is implemented outside
      research settings an impact evaluation is warranted.

PMID- 24295440
TI  - DeNovoGUI: an open source graphical user interface for de novo sequencing of
      tandem mass spectra.
AB  - De novo sequencing is a popular technique in proteomics for identifying peptides
      from tandem mass spectra without having to rely on a protein sequence database.
      Despite the strong potential of de novo sequencing algorithms, their adoption
      threshold remains quite high. We here present a user-friendly and lightweight
      graphical user interface called DeNovoGUI for running parallelized versions of
      the freely available de novo sequencing software PepNovo+, greatly simplifying
      the use of de novo sequencing in proteomics. Our platform-independent software is
      freely available under the permissible Apache2 open source license. Source code,
      binaries, and additional documentation are available at
      http://denovogui.googlecode.com . 

PMID- 24295441
TI  - Parenting a child with a cleft: the father's perspective.
AB  - OBJECTIVE: To explore the impact of having a child born with a cleft lip and/or
      palate from the father's perspective. DESIGN: Individual qualitative telephone
      interviews. PARTICIPANTS: A total of 15 fathers of children born with cleft lip
      and/or palate were recruited throughout the U.K. via advertisements. RESULTS:
      Supported by a number of subthemes, four overarching themes were identified:
      variations in care and support; appraisals of the cleft; perceptions of
      treatment; and looking back and moving forward. CONCLUSIONS: Fathers reported
      experiences comparable to those previously reported by mothers, in addition to a
      number of further support and information needs. PARTICIPANTS played a key role
      in supporting their families through the treatment process, yet fathers are
      underrepresented in the research literature. Recommendations are made for the
      adequate inclusion of fathers in future research and in relation to methods of
      support for fathers through their children's diagnosis and treatment.

PMID- 24295442
TI  - Early lexical characteristics of toddlers with cleft lip and palate.
AB  - Objective : To examine development of early expressive lexicons in toddlers with
      cleft palate to determine whether they differ from those of noncleft toddlers in
      terms of size and lexical selectivity. Design : Retrospective. Patients : A total
      of 37 toddlers with cleft palate and 22 noncleft toddlers. Main Outcome Measures
      : The groups were compared for size of expressive lexicon reported on the
      MacArthur Communicative Development Inventory and the percentage of words
      beginning with obstruents and sonorants produced in a language sample.
      Differences between groups in the percentage of word initial consonants correct
      on the language sample were also examined. Results : Although expressive
      vocabulary was comparable at 13 months of age for both groups, size of the
      lexicon for the cleft group was significantly smaller than that for the noncleft
      group at 21 and 27 months of age. Toddlers with cleft palate produced
      significantly more words beginning with sonorants and fewer words beginning with
      obstruents in their spontaneous speech samples. They were also less accurate when
      producing word initial obstruents compared with the noncleft group. Conclusions :
      Toddlers with cleft palate demonstrate a slower rate of lexical development
      compared with their noncleft peers. The preference that toddlers with cleft
      palate demonstrate for words beginning with sonorants could suggest they are
      selecting words that begin with consonants that are easier for them to produce.
      An alternative explanation might be that because these children are less accurate
      in the production of obstruent consonants, listeners may not always identify
      obstruents when they occur. 

PMID- 24295443
TI  - Polyelectrolyte as solvent and reaction medium.
AB  - A poly(ionic liquid) with a rather low glass transition temperature of -57
      degrees C was synthesized via free radical polymerization of an acrylate-type
      ionic liquid monomer. It exhibits fluidic behavior in a wide temperature range
      from room temperature to the threshold of the thermal decomposition. We
      demonstrate that it could act as a unique type of macromolecular solvent to
      dissolve various compounds and polymers and separate substances. In addition,
      this polyelectrolyte could serve successfully as reaction medium for catalysis
      and colloid particle synthesis. The synergy in the solvation and stabilization
      properties is a striking character of this polymer to downsize the in situ
      generated particles. 

PMID- 24295444
TI  - Dynamic materials from microgel multilayers.
AB  - Multilayer coatings made from hydrogel microparticles (microgels) are
      conceptually very simple materials: thin films composed of microgel building
      blocks held together by polyelectrolyte "glue". However, the apparent simplicity
      of their fabrication and structure belies extremely complex properties, including
      those of "dynamic" coatings that display rapid self-healing behavior in the
      presence of solvent. This contribution covers our work with these materials and
      highlights some of the key findings regarding damage mechanisms, healing
      processes, film structure/composition, and how the variation of fabrication
      parameters can impact self-healing behavior. 

PMID- 24295445
TI  - Latent mean comparisons on the BRIEF in preterm children: parent and teacher
      differences.
AB  - Executive function is a heterogeneous construct applied to cognitive capacities
      that together enable individuals to effectively engage in activities toward a
      purposive goal. Children born at extremely low birth weight (ELBW) are at risk of
      executive dysfunction on performance-based measures. In natural contexts,
      executive function may be described using such parental and teacher
      questionnaires as the Behavior Rating Inventory of Executive Function (BRIEF).
      This study examined the factor structure of the BRIEF-parent form in 124 ELBW
      children and of the BRIEF-teacher form in 90 ELBW children. Although our data
      showed that the fit of a two-factor structure was adequate for the parent report,
      a three-factor model provided advantages over the two-factor model across all fit
      indices and best characterized the data. For teacher report, these data supported
      a three-factor but not a two-factor model. Using the three-factor model for both
      groups of informants, we compared parent and teacher reports (n = 90 pairs)
      between the three identified latent variables. Parents reported significantly
      more difficulty with Emotional Regulation (p < .05), and teachers reported
      significantly more difficulty with Behavioral Regulation (p < .05). No
      significant differences were found between parent and teacher reports for
      Metacognition.

PMID- 24295446
TI  - The effects of heparin binding proteins in platelet releasate on bone formation.
AB  - Platelet releasates (PR) from platelet-rich plasma (PRP) preparations are often
      used as an adjuvant for tissue repair. However, many in vitro and in vivo
      published studies have shown inconsistent results since outcomes depended on the
      methods of PRP preparation, the dosage of PRP and wound repair models used. Among
      the 300 proteins released by platelets, a number of them have the ability to bind
      to heparin, a sulfated glycosaminoglycan well known for its anticoagulant
      activity. In this study, we focused on the heparin binding proteins in PR by
      testing PR with the heparin-heparin binding protein complexes, PR with slow
      releasing heparin binding proteins from agarose-bound heparin, and PR with the
      heparin binding proteins removed. The bone-forming effect of each of these PR as
      an adjuvant to demineralized bone matrix (DBM) was tested. When heparin was added
      to the PR preparation, DBM bone-forming potential was completely lost. However,
      when heparin was added as agarose-bound heparin and co-implanted with DBM, both
      alkaline phosphatase activity and areas of new bone formation increased. The
      study revealed that stripping off heparin binding proteins from PR did not affect
      ectopic DBM bone formation, whereas the controlled release of such proteins
      favors osteoinduction. 

PMID- 24295447
TI  - Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals
      high expression of catabolic bone markers that is modulated by methotrexate.
AB  - INTRODUCTION: We aimed to investigate the expression and therapeutic modulation
      of the receptor activator of the NF-kappaB ligand (RANKL) system in early
      untreated rheumatoid arthritis (RA). METHODS: In this study, 15 patients with
      newly diagnosed RA (median symptom duration 7 months) were started on
      methotrexate (MTX) 20 mg weekly. Synovial biopsies were obtained by needle
      arthroscopy at baseline and 8 weeks after initiation of therapy. X-rays of the
      hands and feet were obtained at baseline and 1 year after diagnosis.
      Immunohistochemistry was performed to detect RANKL, receptor activator of nuclear
      factor-kappaB (RANK) and osteoprotegerin (OPG) in the synovial biopsies. The in
      vitro effect of MTX was tested on RA-derived primary fibroblasts and the
      osteoblasts-like osteosarcoma cell line (rtPCR, Western blot and ELISA) and in
      osteoclasts (tartrate-resistant acid phosphatase staining and dentine pit
      formation assay). RESULTS: MTX decreased synovial cellularity as well as RANK
      expression and the RANKL/OPG ratio. We confirmed this effect by a decrease of the
      mRNA and protein RANKL/OPG ratio in synovial-derived fibroblasts and osteoblasts
      like tumoral cells exposed in vitro to methotrexate. Supernatants from MTX
      treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the
      absence of exogenous RANKL. Furthermore, MTX blocked osteoclastogenesis from
      peripheral blood mononuclear cells despite the presence of macrophage colony
      stimulating factor and RANKL, which indicates that MTX directly inhibits
      osteoclastogenesis. CONCLUSIONS: The synovial membrane of early-untreated RA is
      characterized by a high RANKL/OPG ratio that can be reversed by methotrexate.

PMID- 24295449
TI  - Orientational ordering of passivating ligands on CdS nanorods in solution
      generates strong rod-rod interactions.
AB  - We present the first nearly atomistic molecular dynamics study of nanorod-nanorod
      association in explicit solvent, showing that inter-rod forces can be dominated
      by microscopic factors absent in common continuum descriptions. Specifically, we
      find that alkane ligands on faceted CdS nanorods in n-hexane undergo a
      temperature-dependent order-disorder transition akin to that of self-assembled
      monolayers on macroscopic substrates. This collective ligand alignment organizes
      nearby solvent molecules, strongly influencing the statistics of rod-rod
      separation. The strong temperature dependence of this mechanism could be
      exploited in the laboratory to manipulate and optimize the assembly of ordered
      structures. 

PMID- 24295448
TI  - The Bacillus BioBrick Box: generation and evaluation of essential genetic
      building blocks for standardized work with Bacillus subtilis.
AB  - BACKGROUND: Standardized and well-characterized genetic building blocks are a
      prerequisite for the convenient and reproducible assembly of novel genetic
      modules and devices. While numerous standardized parts exist for Escherichia
      coli, such tools are still missing for the Gram-positive model organism Bacillus
      subtilis. The goal of this study was to develop and thoroughly evaluate such a
      genetic toolbox. RESULTS: We developed five BioBrick-compatible integrative B.
      subtilis vectors by deleting unnecessary parts and removing forbidden restriction
      sites to allow cloning in BioBrick (RFC10) standard. Three empty backbone vectors
      with compatible resistance markers and integration sites were generated, allowing
      the stable chromosomal integration and combination of up to three different
      devices in one strain. In addition, two integrative reporter vectors, based on
      the lacZ and luxABCDE cassettes, were BioBrick-adjusted, to enable beta
      galactosidase and luciferase reporter assays, respectively. Four constitutive and
      two inducible promoters were thoroughly characterized by quantitative, time
      resolved measurements. Together, these promoters cover a range of more than three
      orders of magnitude in promoter strength, thereby allowing a fine-tuned
      adjustment of cellular protein amounts. Finally, the Bacillus BioBrick Box also
      provides five widely used epitope tags (FLAG, His10, cMyc, HA, StrepII), which
      can be translationally fused N- or C-terminally to any protein of choice.
      CONCLUSION: Our genetic toolbox contains three compatible empty integration
      vectors, two reporter vectors and a set of six promoters, two of them inducible.
      Furthermore, five different epitope tags offer convenient protein handling and
      detection. All parts adhere to the BioBrick standard and hence enable
      standardized work with B. subtilis. We believe that our well-documented and
      carefully evaluated Bacillus BioBrick Box represents a very useful genetic tool
      kit, not only for the iGEM competition but any other BioBrick-based project in B.
      subtilis.

PMID- 24295450
TI  - Combination of cancer immunotherapy with clinically available drugs that can
      block immunosuppressive cells.
AB  - Although cancer immunotherapy, which is able to target specifically cancer cells
      without detrimental effects to normal cell functions, would serve as an ideal
      therapeutic modality, most of the randomized clinical trials of cancer
      immunotherapy have not demonstrated a meaningful survival benefit to cancer
      patients over preexisting therapeutic modalities. Due to the discrepancy between
      the impressive preclinical results and the limited clinical results, the cancer
      immunotherapy is not accepted generally as a standard therapy for cancers. A
      variety of immune escape mechanisms are thought to be involved in this
      ineffectiveness of cancer immunotherapy. Therefore, elimination of
      immunosuppressive activities in tumor microenvironment will enhance the
      effectiveness of cancer immunotherapy, which is currently focused on activation
      of tumor-specific immune responses. Since there are now increasing evidences
      showing that many cytotoxic anticancer drugs including targeted agents given in
      lower-than-therapeutic doses have not only the ability to eliminate tumor cells
      but can also block the immunosuppressive activities in tumor microenvironments
      and consequently favor the development of anticancer immune responses, clinically
      available drugs can be considered for their rapid application to cancer
      immunotherapies to enhance the efficacy of cancer immunotherapies with marginal
      effects on cancer treatment.

PMID- 24295451
TI  - Alveolar Cleft Restoration Using Autogenous Tooth Bone Graft Material for Implant
      Placement: A Case Report.

PMID- 24295453
TI  - Recollections of how the journal Psychotherapy came to be.
AB  - The founding Editor of Psychotherapy offers some recollections of how the journal
      Psychotherapy came into being, and also provides a larger professional context
      for this event in the American Psychological Association at that time.

PMID- 24295452
TI  - Pro-apoptotic and immunostimulatory tetrahydroxanthone dimers from the endophytic
      fungus Phomopsis longicolla.
AB  - Four tetrahydroxanthone dimers (1-4) and four biogenetically related monomers (5
      8), including the new derivatives 4-6, were isolated from the endophyte Phomopsis
      longicolla. The absolute configurations of 2-4 were established for the first
      time by TDDFT electronic circular dichroism calculations, and that of
      phomoxanthone A (1) was revised by X-ray crystallography. Phomoxanthone A (1)
      showed the strongest pro-apoptotic activity when tested against a panel of human
      cancer cell lines, including cisplatin-resistant cells, whereas it was up to 100
      fold less active against healthy blood cells. It was also the most potent
      activator of murine T lymphocytes, NK cells, and macrophages, suggesting an
      activation of the immune system in parallel to its pro-apoptotic activity. This
      dual effect in combating cancer cells could help in fighting resistance during
      chemotherapy. Preliminary structure-activity studies of isolated compounds and
      derivatives obtained by semisynthesis (9a-11) hinted at the location of the
      biaryl axis and the presence of acetyl groups as important structural elements
      for the biological activity of the studied tetrahydroxanthones.

PMID- 24295454
TI  - An editor's memoir: reflections and premonitions.
AB  - The author served as the second Editor of this journal. In the article that
      follows, he reminisces about the state of the publication when he assumed
      responsibility for it and comments on the nature of the profession during the
      time of his incumbency. He reflects on the creative innovation and ferment in
      both the theories and tactics of psychotherapy unfolding during the 1970s and
      closes with statements of concern about developments within the field that are
      ominous and have come to the fore over the decades since he left office in 1983.

PMID- 24295455
TI  - A decade of editing.
AB  - The author reviews his term as editor of Psychotherapy (1984-1993), with a
      historical look at the beginnings of the publication, a content analysis of
      articles, and commentary on trends in the field during that time. He also shares
      some highlights and experiences as an editor.

PMID- 24295456
TI  - Psychologists conducting Psychotherapy in 2012: current practices and historical
      trends among Division 29 members.
AB  - This study updates three similar investigations conducted in 1981, 1991, and 2001
      on APA Division of Psychotherapy members in order to paint a contemporary
      portrait of psychologists conducting psychotherapy and to chronicle historical
      trends among Division 29 members. Four hundred twenty-eight psychologists (43%
      response) completed a questionnaire in 2012 regarding their demographic
      characteristics, professional activities, theoretical orientations, employment
      settings, and career experiences. The results point to an increasingly female and
      aging membership, which continues to be employed primarily in private practices
      and universities. Psychodynamic (27%), integrative (25%), and cognitive (17%)
      orientations continue to prevail. Professional activities have remained quite
      similar across the past 30 years with the exception of declines in projective
      testing and growth in neuropsychological and health testing. Training and career
      satisfactions remain high as well.

PMID- 24295457
TI  - Early career perspectives on psychotherapy research and practice: psychotherapist
      effects, multicultural orientation, and couple interventions.
AB  - I was awarded the Early Career Award from Division 29 and the American
      Psychological Foundation (APF) in 2012, and in this article, I provide an
      overview of my psychotherapy research career and insight gained along the way.
      Specifically, I will cover 3 main areas of my research: (a) psychotherapist
      effects, (b) multicultural processes in psychotherapy, and (c) romantic
      relationship interventions. First, although it is well known that some
      psychotherapists are better than others, the source of this expertise is not well
      understood. Across my studies, I have found notable variability in the ways that
      psychotherapists are able to effectively engage clients during sessions and this
      may be a key source of psychotherapist effectiveness. Next, I provide an overview
      of my studies examining clients' perceptions of their psychotherapists'
      multicultural orientation (MCO). For instance, across 9 studies, clients'
      perceptions of their psychotherapists' MCO accounted for 4% to 5% of the variance
      in clients' psychological well-being and was strongly associated with clients'
      alliance scores (weighted rs |.30| to |.64|). I also comment on the role of
      commitment in couple psychotherapy, by highlighting the importance of commitment
      uncertainty. Lastly, I provide some comments looking forward to potential themes
      in psychotherapy research and practice.

PMID- 24295458
TI  - Introduction to special section on clients' perspective of change in
      psychotherapy.
AB  - The articles included in this special section are based on the works presented in
      a panel named Clients Talking About Therapy, which took place during the 43rd
      International Annual Meeting of the Society for Psychotherapy Research in
      Virginia Beach. One of the main issues at the time of the panel was the
      difficulty in reaching an agreement about what change represents in psychotherapy
      research. In this introduction I very briefly present some of the debates that
      are currently going on about change and the role of qualitative research in that
      debate. The articles included are qualitative investigations that study the value
      of clients' perspectives from different vantage points. The authors used in-depth
      interviews, which allow interviewees to communicate whatever they think, enabling
      the emergence of new perspectives. I look forward to the application of the
      information obtained among these studies, in the development of applied clinical
      knowledge.

PMID- 24295459
TI  - A qualitative investigation of former clients' perception of change, reasons for
      consultation, therapeutic relationship, and termination.
AB  - The purpose of this research is to investigate former client's perception of
      change, reasons for consultation, therapeutic relationship, and termination.
      Semistructured interviews were conducted with 17 former clients who had been in a
      psychotherapeutic treatment. A qualitative approach, based on consensual
      qualitative research (CQR) was used to analyze the interviews. Results show how
      the balance of negative and positive aspects of the therapeutic relationship is
      associated with the perception of change. Likewise, categories related to reasons
      for consultation were associated with types of change and therapy termination.
      The relevance of the client's perspective is increasingly being recognized as
      valuable for the understanding of the psychotherapeutic processes and generates
      hypotheses for future research.

PMID- 24295460
TI  - Differential client perspectives on therapy in Argentina and the United States: a
      cross-cultural study.
AB  - Although there is a growing body of research in both cross-cultural issues in
      psychotherapy and in the client's perspective, little is known about differences
      or similarities in the way clients from different cultures, particularly those
      from different nations, subjectively experience therapy. The present study
      addressed this gap through a qualitative analysis of interviews with former
      therapy clients in Argentina and the United States. The researchers used a
      consensual qualitative research (CQR; C. E. Hill, B. J. Thompson, & E. N.
      Williams, 1997, A guide to conducting consensual qualitative research, The
      Counseling Psychologist, Vol. 25, pp. 517-572; C. E. Hill, S. Knox, B. J.
      Thompson, E. N. Williams, S. A. Hess, & N. Ladany, 2005, Consensual qualitative
      research: An update, Journal of Counseling Psychology, Vol. 52, pp. 196-205)
      methodology and provide illustrative examples from the raw transcripts. Among
      other differences, Argentine and U.S. participants differed in their experience
      of the therapy setting, the interventions their therapists used, and in the types
      of change they reported to result from therapy. Also notable, Argentine
      participants spoke a great deal more about change than U.S. participants. Results
      are preliminary, but provide implications for the adaptation of treatments to
      different cultures and for the cross-cultural validity of researchers' and
      policymakers' current definitions of treatment efficacy.

PMID- 24295461
TI  - Assessing client self-narrative change in emotion-focused therapy of depression:
      an intensive single case analysis.
AB  - Personality researchers use the term self-narrative to refer to the development
      of an overall life story that places life events in a temporal sequence and
      organizes them in accordance to overarching themes. In turn, it is often the case
      that clients seek out psychotherapy when they can no longer make sense of their
      life experiences, as a coherent story. Angus and Greenberg (L. Angus and L.
      Greenberg, 2011, Working with narrative in emotion-focused therapy: Changing
      stories, healing lives. Washington, DC: American Psychological Association Press)
      view the articulation and consolidation of an emotionally integrated self
      narrative account as an important part of the therapeutic change process that is
      essential for sustained change in emotion-focused therapy of depression. The
      purpose of the present study was to investigate client experiences of change, and
      self-narrative reconstruction, in the context of one good outcome emotion-focused
      therapy dyad drawn from the York II Depression Study. Using the Narrative
      Assessment Interview (NAI) method, client view of self and experiences of change
      were assessed at three points in time--after session one, at therapy termination,
      and at 6 months follow-up. Findings emerging from an intensive narrative theme
      analyses of the NAI transcripts--and 1 key therapy session identified by the
      client--are reported and evidence for the contributions of narrative and emotion
      processes to self-narrative change in emotion-focused therapy of depression are
      discussed. Finally, the implications of assessing clients' experiences of self
      narrative change for psychotherapy research and practice are addressed.

PMID- 24295462
TI  - Windows into clients' perspectives on psychotherapy.
AB  - In this brief discussion I highlight some dimensions of Angus and Kagan's (2013);
      Olivera, Braun, Gomez Penedo, and Roussos (2013); and Jock, Bolger, Olivera, and
      Roussos (2013) articles that are of particular interest to me. Reading their
      articles has served as a catalyst for me to reflect at a more general level on
      the state of the art of qualitative methods in psychotherapy research, and to
      articulate some informal reflections about qualitative research.

PMID- 24295463
TI  - Cognitive behavioral therapy for bulimia nervosa.
AB  - Cognitive-behavioral therapy (CBT) is a first-line psychotherapeutic treatment
      for bulimia nervosa (BN). This article outlines three specific interventions-
      introducing and using the CBT model of BN, self-monitoring of eating and related
      experiences, and psychoeducation regarding various aspects of BN--representative
      of CBT overall but unique in their application to individuals with BN. The
      theoretical basis and supporting research relevant to each technique are
      highlighted. Clinical vignettes are provided to illustrate how these
      interventions might be integrated into the psychotherapy.

PMID- 24295464
TI  - Targeting binge eating through components of dialectical behavior therapy:
      preliminary outcomes for individually supported diary card self-monitoring versus
      group-based DBT.
AB  - The current study examined two condensed adaptations of dialectical behavior
      therapy (DBT) for binge eating. Women with full- or sub-threshold variants of
      either binge eating disorder or bulimia nervosa were randomly assigned to
      individually supported self-monitoring using adapted DBT diary cards (DC) or
      group-based DBT, each 15 sessions over 16 weeks. DC sessions focused on problem
      solving diary card completion issues, praising diary card completion, and
      supporting nonjudgmental awareness of eating-related habits and urges, but not
      formally teaching DBT skills. Group-based DBT included eating mindfulness,
      progressing through graded exposure; mindfulness, emotion regulation, and
      distress tolerance skills; and coaching calls between sessions. Both treatments
      evidenced large and significant improvements in binge eating, bulimic symptoms,
      and interoceptive awareness. For group-based DBT, ineffectiveness, drive for
      thinness, body dissatisfaction, and perfectionism also decreased significantly,
      with medium to large effect sizes. For DC, results were not significant but large
      in effect size for body dissatisfaction and medium in effect size for
      ineffectiveness and drive for thinness. Retention for both treatments was higher
      than recent trends for eating disorder treatment in fee-for-service practice and
      for similar clinic settings, but favored DC, with the greater attrition of group
      based DBT primarily attributed to its more intensive and time-consuming nature,
      and dropout overall associated with less pretreatment impairment and greater
      interoceptive awareness. This preliminary investigation suggests that with both
      abbreviated DBT-based treatments, substantial improvement in core binge eating
      symptoms is possible, enhancing potential avenues for implementation beyond more
      time-intensive DBT.

PMID- 24295465
TI  - The good news about psychotherapy for eating disorders: comment on Warren,
      Schafer, Crowley, and Olivardia.
AB  - Therapists and nontherapists alike commonly misperceive the treatment of eating
      disorders as particularly challenging and unpleasant. In addition to the Warren,
      Schafer, Crowley, and Olivardia (2013, pp. 553-564) study, additional research
      suggests that the general public and therapists who do not regularly treat eating
      disorders share some misinformation regarding the experience of psychotherapy
      with patients with eating disorders and the responsiveness of these patients to
      treatment. In fact, the sample described in the Warren et al. (2013) study, as
      well as many other experienced clinician samples, report far more positive
      experiences treating eating disorders than negative ones (Thompson-Brenner,
      Satir, Franko, & Herzog, 2012). Specific measures should be taken to (1) address
      misinformation in the field, and (2) to support inexperienced therapists to
      promote their success treating patients with eating disorders.

PMID- 24295472
TI  - Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by
      diallyl trisulfide.
AB  - The present investigation was aimed to investigate the possible protective role
      of diallyl trisulfide (DATS) against arsenic (As)-induced hepatic mitochondrial
      toxicity in rats. Mitochondria were isolated from the liver tissue of rats from
      all the groups. Lipid profile, lipid peroxidation, antioxidant enzyme activities,
      hepatic function enzymes, mitochondrial swelling, cytochrome c oxidase activity,
      mitochondrial Ca(+)-ATPase and Na(+)/K(+)-ATPase activity, mitochondrial calcium
      content and mitochondrial enzyme activities were measured. Short-term As exposure
      (5 mg/kg bw/d for 28 d) caused liver damage as evidenced by changes in activities
      of liver enzymes. The effects of As were coupled with enhanced reactive oxygen
      species generation, mitochondrial swelling, inhibition of cytochrome c oxidase,
      complex I-mediated electron transfer, decreased Ca(2+)-ATPase and Na(+)/K(+)
      ATPase activity, a reduction in mitochondrial calcium content, changes in indices
      of hepatic mitochondrial oxidative stress, significant increase in mitochondrial
      lipid peroxidation products and alterations in mitochondrial lipid profile.
      Significant decreases in mitochondrial antioxidants and tricarboxylic acid cycle
      enzymes were also found in the liver mitochondria of As-induced hepatic
      mitochondrial toxicity in rats. As also increased hepatic caspase-3 activity and
      DNA fragmentation. All these apoptosis-related molecular changes caused by As
      could be alleviated by supplementation with DATS, which likely suggests a
      protective role against As-induced hepatotoxic changes and hepatic mitochondrial
      toxicity. The protective effect of DATS on the liver mitochondria was evidenced
      by altering all the changes induced by As. Free radical scavenging and metal
      chelating activities of DATS may be the mechanism, responsible for the protective
      action against As-induced mitochondrial damage in liver.

PMID- 24295473
TI  - Identification of novel biomarkers of brain damage in patients with hemorrhagic
      stroke by integrating bioinformatics and mass spectrometry-based proteomics.
AB  - Hemorrhagic stroke (HS) is a significant cause of mortality that requires rapid
      diagnosis and prompt medical attention. A time-efficient diagnostic test to
      assist in the early classification of patients with stroke would be of great
      value. The aims here were to (a) select "brain-specific" proteins using a
      bioinformatics approach, (b) develop selected reaction monitoring (SRM) assays
      for candidate proteins, and (c) quantify these proteins in cerebrospinal fluid
      (CSF). "The Human Protein Atlas" and the "Peptide Atlas" were used to select
      proteins specifically and abundantly expressed in brain tissue, excluding high
      abundance plasma proteins. Protein extracts from brain tissue were used for SRM
      assay development of proteins of interest. The levels of 68 "brain-specific"
      proteins were measured by SRM in 36 age-matched patients, including individuals
      with HS (n = 15), ischemic stroke (n = 11), and controls (n = 10). Additionally,
      S100B was measured using an electrochemoluminometric immunoassay. CSF levels of
      S100B and eight of the "brain-specific" proteins (NSE, GFAP, alpha-Inx, MBP, MT3,
      NFM, beta-Syn, and gamma-Syn) were increased in a subset of samples from HS
      patients, especially in those individuals with intraventricular hemorrhage and
      poor outcome. Seven of these proteins (S100B, NSE, GFAP, alpha-Inx, MBP, NFM, and
      beta-Syn) showed significant differences between patients with and without brain
      hemorrhage. Novel biomarkers of brain injury (alpha-Inx, NFM, and beta-Syn) were
      identified in the CSF of patients with HS. Investigating the role of these
      proteins in blood with more sensitive methods is warranted. 

PMID- 24295475
TI  - [Are antibiotics necessary in the treatment of uncomplicated diverticulitis?].
AB  - INTRODUCTION: This paper deals with the results of recently published studies on
      the importance of the use of antibiotics in the treatment of uncomplicated
      diverticulitis. It is based on the articles available in the Medline database.
      CONCLUSION: The prevalence of diverticulosis in the developed countries of the
      Western world is increasing and, along with it, the costs of treatment of
      diverticulitis. The use of antibiotics in the treatment of uncomplicated
      diverticulitis does not reduce the incidence of complications or shorten the
      treatment, nor does it reduce the risk of recurrence.

PMID- 24295474
TI  - Intracellular NF-kB-decrease and IKBalpha increase in human macrophages following
      CTLA4-Ig treatment.
AB  - OBJECTIVES: The transcription factor NF-kB is involved in the expression of
      several genes linked to the immune response, including those of pro-inflammatory
      cytokines. We investigated cytokine production and NF-kB expression following
      CTLA4-Ig (abatacept) treatment of cultured human macrophages. METHODS: Human THP1
      cells, differentiated in macrophages, were treated with CTLA4-Ig (100, 500
      MUg/ml; 3,12,24 hours). Quantitative RT-PCR analysis (qRT-PCR) of mRNA for NF-kB,
      IKBalpha and for IL-6, TNF-alpha, IL-1beta, was performed after 3 and 12 hours
      from treatment. Western blot (WB) analysis for NF-kB and IKBalpha was performed
      after 24 hours from treatment. RESULTS: NF-kB gene expression was significantly
      downregulated (p<0.05), at 3 and 12 hours from CTLA4-Ig treatment, vs. untreated
      cells (cnt). IKBalpha resulted significantly increased vs. cnt (p<0.05), at 12
      hours from CTLA4-Ig [500 MUg/ml] treatment. After 3 hours, CTLA4-Ig [100 MUg/ml]
      induced a significant decrease of TNF-alpha and IL-6 (p<0.05), vs. cnt and CTLA4
      Ig [500 MUg/ml] further reduced TNF-alpha (p<0.001), vs. cnt. After 12 hours from
      CTLA4-Ig treatment, a significant downregulation for IL-6 and IL1beta expression
      (p<0.001), vs. cnt, was still evident. Results were confirmed by WB. CONCLUSIONS:
      NF-kB pathway seems to be implicated in the CTLA4-Ig modulation of macrophage
      cytokine expression. NF-kB expression resulted downregulated while its
      cytoplasmatic inhibitor IKBalpha was increased.

PMID- 24295476
TI  - [The cost of surgical and endovascular treatment of abdominal aortic aneurysm - a
      retrospective comparative study].
AB  - INTRODUCTION: A comparison of the costs of a surgery and an endovascular
      treatment of abdominal aortic aneurysms (AAA) for the General Health Insurance
      Company (VsZP) in 2009-2010. MATERIAL AND METHODS: Between 2009 and 2010, VsZP
      paid for treatment of 211 patients with AAA with an average age of 69 years
      (range: 41-91 years). Out of these, 174 patients underwent surgical treatment and
      37 patients were treated by endovascular means. In both groups, we observed a
      total cost of treatment, payment for hospitalization (UH) and separately charged
      material (ZM), the cost of blood and reimbursement for CT (computer tomography)
      examinations and the patient age. For statistical comparison, we used the
      nonparametric Mann-Whitney U test, the limit of statistical significance was
      <0.01. The data were processed and compared by means of contingency tables in MS
      Excel and then statistically processed in the program StatSoft, Inc.. (2011).
      STATISTICA (data analysis software system), version 10th www.statsoft.com.
      RESULTS: The total two-year costs of VsZP for the treatment of AAA were ? 1 212
      188 - out of which 37% were represented by the OR costs (open repair) and 63% for
      EVAR (endovascular aneurysm repair) (p <0.01). In terms of the ZM use (p <0.01),
      and the use of CT examinations (p <0.01), EVAR is cost demanding. OR is cost
      demanding in terms of the blood consumption levels (p <0.01). The average total
      cost per admission was ? 21,038 for EVAR and ? 2,493 for OR, representing only
      12% of the total EVAR costs. The age of patients has no impact on the costs (p>
      0.01). The decisive impact on the total costs is represented by ZM, which
      presents 90 % of costs of EVAR method and 44% of OR method. CONCLUSION: OR and
      EVAR are effective modalities for the treatment of AAA. EVAR is a minimally
      invasive method, but the treatment costs are more than 8 times higher than the
      costs of surgical treatment. In terms of the VsZP cost control for the treatment
      of AAA, there must be clearly defined explicit indication criteria for EVAR. In
      terms of the costs for the treatment of AAA with "good risk" patients and those
      cases where there are no local obstacles for the surgical treatment (eg,
      colostoma, hostile abdomen, ren arcuatus and other), the surgical therapy is a
      "gold" standard. The health insurance company is a crucial regulator of the
      system of payment for provided medical care. The development of medical
      technology and the financial burden, on one hand, and the limited and scarce
      resources, on the other hand, are a source of "tension" between the health care
      providers and the regulators (insurance, Ministry of Health). One way to slow the
      "opening of the scissors" is to establish clear rules for the entry of new
      technologies into clinical practice, clearly defined costs (COI - cost of
      illness), and the usefulness and cost-effectiveness (CEA - cost-effectiveness
      analysis, ICER - incremental cost-effectiveness ratio, QALY - quality-adjusted
      life year). Despite the fact that it has beenmore than 20 years after the "velvet
      revolution", implementing the principles of health economics and health
      technology into practice has been managed in a rather weak way. The comparison of
      the costs of treatment is applicable in many areas of clinical medicine, and in
      the case of well-defined data it can be a source for the determination of ICER,
      CEA and QALYs. Key words: abdominal aortic aneurysms - surgery and endovascular
      treatment - costs.

PMID- 24295477
TI  - [Treatment strategies of the colorectal anastomosis stricture].
AB  - INTRODUCTION: The treatment of the stenoses of colorectal anastomoses represents
      a difficult area of colonic surgery. This is partly connected to the introduction
      of staplers and an increasing amount of sphincter-preserving surgeries. At our
      clinic, we solve the stenoses of colorectal anastomoses using a surgical
      rectoscope with a good effect. MATERIAL AND METHODS: We analysed retrospectively
      a group of 27 patients with benign stenosis of colorectal anastomosis of the
      medial and upper rectum who underwent surgery at our clinic in the period between
      January 2004 and December 2011. From the total amount of 27 patients, in 23
      patients the stenosis was caused by the dehiscence of anastomosis, and in 4
      patients the stenosis had a different etiology. RESULTS: In the group of 27
      patients, in 14 patients the stenosis of colorectal anatomosis was solved
      radiologically using a high pressure balloon. Total of 13 patients underwent
      surgery, in 10 of them we used the surgical rectoscope and 3 patients underwent
      an open abdominal procedure. CONCLUSION: The first method of choice in treatment
      of the stenoses of the colorectal anastomoses is a balloon dilatation. If this is
      not successful we can use the surgical rectoscope as a minimally invasive though
      effective and safe method.

PMID- 24295478
TI  - [Recurrent diverticulitis - risk factors].
AB  - INTRODUCTION: Colonic diverticular disease is a common illness, especially in the
      elderly population. It may be asymptomatic and cause chronic intestinal problems,
      colonic diverticular bleeding or inflammatory complications with considerable
      morbidity and mortality. We have attempted at finding factors that would help us
      identify patients with a higher risk of diverticulitis recurrence as well as
      patients with a higher likelihood of perforated diverticulitis. MATERIAL AND
      METHODS: This retrospective study included all patients admitted to our surgical
      ward for inflammatory complications of diverticular disease between 2000 and
      2012: 278 patients, 88 men and 190 women. We looked up the first attack of
      diverticulitis in our documentation as well as the relapses, if any, their number
      and course, and the time from the first attack to the relapse. We analyzed the
      influence of age, gender, comorbidities (diabetes mellitus, overweight, ischemic
      heart disease, chronic renal failure, gastroduodenal disease), nicotine abuse and
      medication (glucocorticoids and other immunosuppressive drugs, acetylsalicylic
      acid) on diverticulitis recurrence and its complicated course. We compared the
      results of conservative and surgical therapy. Statistical analysis was performed
      using Fishers exact test and Man-Whitney U tests. RESULTS: We did not demonstrate
      any statistically significant dependence of diverticulitis recurrence on age or
      gender. Colectomy (both acute and elective surgery) clearly decreases the
      likelihood of recurrence (p=0.00007). Comorbidities, nicotine abuse and
      medication were not associated with an increased risk of recurrence. Steroid and
      immunosuppressive drugs use was significantly associated with higher perforation
      rates, without impacting on the likelihood of recurrence. Regular smoking of
      cigarettes had no impact on recurrence or on its severity. CONCLUSION: We did not
      find any reliable indicator of recurrent diverticulitis. Age, gender,
      comorbidities, smoking and medication are not significant. Immunocompromised
      patients have a higher probability of perforation and a more serious course of
      the illness. The problem is, however, that complicated diverticulitis is often
      the initial clinical presentation of the disease. Surgical treatment is more
      effective than conservative therapy in the prophylaxis of recurrent
      diverticulitis, but, according to our as well as foreign data, the relapse of
      diverticulitis occurs in a minority of the patients (14% in our study) and the
      recurrence tends to have a relatively benign course. These findings should be
      taken into consideration when counselling patients regarding potential benefits
      of prophylactic colectomy.

PMID- 24295479
TI  - [Chronic abdominal pain with a rare cause].
AB  - The authors use a case report of a female patient with chronic abdominal pain
      progressing postprandially as an example to demonstrate the complexity of the
      diagnostic process in patients with these complaints, as well as a surprising
      peroperative finding in which a small neuroendocrine tumour of the small
      intestine was the cause of the difficulties. The ensuing discussion also deals
      with other possible causes of chronic abdominal pain associated with eating
      disorders.

PMID- 24295480
TI  - [Not Available].

PMID- 24295481
TI  - [Trochanteric fractures - general overview].
AB  - The current possibilities concerning selection of implants and the respective
      devices provide us with good prerequisites for a successful treatment of almost
      all trochanteric fractures. The basis is a proper evaluation of the type of the
      fracture and respecting its biomechanical features. Based on this analysis we
      select the implant and the proper operative technique. Quality is the highest
      priority as concerns the actual operation. A number of patients tolerate only one
      operation and it is better if it takes 10 minutes more than if it is performed
      improperly. The so called implant failure is in most cases the surgeones failure.

PMID- 24295482
TI  - [Trochanteric fractures - anatomy and classification].
AB  - Classification of trochanteric fractures remains an unresolved issue. While the
      basic division into pertrochanteric and intertrochanteric fractures is valid, it
      is necessary to re-assess the existence of individual subtypes included in AO
      classification. The same applies to the concept of instability of trochanteric
      fractures. In this respect it is necessary to focus more on the lateral
      trochanteric wall and primarily on the effect of medial displacement of the
      femoral shaft in fractures treated by DHS.

PMID- 24295483
TI  - [Trochanteric fractures - implants].
AB  - The current market offers a wide range of extra- and intramedullary implants.
      Their selection should be based on a careful consideration of their design,
      biomechanical properties and last but not least the quality of the
      instrumentation set. Mainly this may substantially influence a smooth course of
      the operation.

PMID- 24295484
TI  - [Trochanteric fractures - operative technique].
AB  - The current offer of implants in combination with preoperative analysis of the
      fracture, selection of an optimal implant and proper operative technique provides
      us with the possibility of a successful treatment of almost all trochanteric
      fractures. One of the main causes of a high number of complications is lack of
      the surgeones experience. Trochanteric fractures are very often operated on by
      young surgeons who do not have sufficient experience, skills and knowledge of
      this issue. In the absence of an experienced senior assistant during operation
      they may grossly violate the basic principles which may result in the subsequent
      failure of internal fixation. If we respect biomechanical principles, select an
      optimal implant and a proper operative technique, we may treat successfully
      almost all trochanteric fractures.

PMID- 24295485
TI  - [Nailing of pertrochanteric fractures - operative technique].
AB  - Nailing of pertrochanteric fractures is indicated when DHS is associated with
      high rate of complications. Thus in unstable comminuted fractures, mainly with
      posterolateral defect and instability, with Adam's arch defect and medial
      instability and in cases when fracture line extends into the subtrochanteric
      region. The increase in number of nailed pertrochanteric fractures has both its
      rational and irrational reasons; irrational, as until now there is no clear
      evidence, that nailing is a faster, safer and easier procedure with a lower rate
      of complications compared with DHS, a rational, as a proven increase in number of
      unstable and comminuted fractures has to be reflected in treatment changes. Thus,
      with respecting the operative techniques principles, intramedullary nailing
      provides evident biomechanical advantages with the possibility of full weight
      bearing and a very low rate of complications.

PMID- 24295486
TI  - [Nailing of inter- and subtrochanteric fractures - operative technique].
AB  - Intertrochanteric and subtrochanteric fractures are a quite heterogeneous and
      imprecisely defined group of fractures. These fractures can be essentially
      divided into two basic groups. The first one belongs to trochanteric fractures.
      In the AO/ASIF classification; these fractures are called intertrochanteric
      (31A3). In the second group, the term subtrochanteric fracture is used by most
      authors for fractures about 5 cm distally from lesser trochanter. In both
      intertrochanteric and subtrochanteric fractures, the proximal fragment is formed
      by femoral head, neck and greater trochanter including its base with vastus ridge
      (tuberculum vastoadductorium or innominate tubercle). On this tubercle, the
      gluteus medius muscle (proximally) and the origin of the vastus lateralis muscle
      (distally) are attached. Tension of these muscles may cause dislocation of the
      proximal fragment. For this reason, reduction of the fracture can be troublesome
      and it is more difficult than in pertrochanteric fractures It seems that
      intramedullary nailing will remain the favorite technique of most of the surgeons
      dealing with intertrochanteric and subtrochanteric fractures. We use short
      reconstruction nail in intertrochanteric fractures. It is useful to use long
      reconstruction nail in subtrochanteric fractures. Distal locking of the nail is
      necessary. Dynamic distal locking is preferred because the two main fragments are
      compressed along the axis of the nail. The number of complications was largely
      related to technical errors, such as insufficient reduction or an incorrectly
      inserted implant. No implant can compensate for errors due to surgery. Serious
      complications can be reduced by the correct assessment of fracture type, the use
      of an appropriate operative technique and early treatment of potential
      complications. The necessity of restoring continuity in the medial cortex of the
      femoral neck (Adams arch) is the requirement that should be observed.
      Pseudoarthrosis or varus malalignment in a healed hip should be managed by valgus
      osteotomy. When the femoral head or the acetabulum is damaged, total hip
      arthroplasty is indicated. A prerequisite for successful surgical outcome is
      urgently and correctly performed osteosynthesis allowing for early rehabilitation
      and mobilisation of the patient.

PMID- 24295488
TI  - Risk factors for contracting watery diarrhoea in Kadoma City, Zimbabwe, 2011: a
      case control study.
AB  - BACKGROUND: Kadoma City experienced an increase in watery diarrhoea from 27 cases
      during week beginning 5th September, to 107 cases during week beginning 26th
      September 2011. The weekly diarrhoea cases crossed the threshold action line
      during week beginning 5th September at the children's clinic in Rimuka Township,
      and the remaining four clinics reported cases crossing threshold action lines
      between week beginning 12th September and week beginning 26th September. Eighty
      two percent of the cases were children less than 5 years old. We conducted a case
      controlstudy to determine risk factorsfor contracting watery diarrhoea in
      children less than 5 years in Kadoma City. METHODS: An unmatched 1:1 case control
      study was conducted in Ngezi and Rimuka townships in Kadoma City, Zimbabwe. A
      case was a child less than 5 years old, who developed acute watery diarrhoea
      between 5th September and 1st October 2011. A control was a child less than 5
      years old who stayed in the same township and did not suffer from diarrhoea. A
      structured questionnaire was administered to caregivers of cases and
      controls.Laboratory water quality tests and stool test results were reviewed.Epi
      InfoTM statistical software was used to analyse data. RESULTS: A total of 109
      cases and 109 controls were enrolled. Independent protective factors were: having
      been exclusively breastfed for six months [AOR = 0.44; 95% CI (0.24-0.82)]; using
      municipal water [AOR = 0.38; 95% CI (0.18-0.80)]; using aqua tablets, [AOR =
      0.49; 95% CI (0.26-0.94)] and; storing water in closed containers, [AOR = 0.24;
      95% CI (0.07-0.0.83). The only independent risk factor for contracting watery
      diarrhoea was hand washing in a single bowl, [AOR = 2.89; 95% CI (1.33-6.28)].
      Salmonella, Shigella, Rotavirus, and Enteropathogenic Escherichia coli were
      isolated in the stool specimens. None of the 33 municipal water samples tested
      showed contamination with Escherichia coli, whilst 23 of 44 (52%) shallow well
      water samples and 3 of 15(20%) borehole water samples tested were positive for
      Escherichia coli. CONCLUSIONS: The outbreak resulted from inadequate clean water
      and use of contaminated water. Evidence from this study was used to guide public
      health response to the outbreak.

PMID- 24295489
TI  - CIMS sulfuric acid detection efficiency enhanced by amines due to higher dipole
      moments: a computational study.
AB  - Quantum chemical calculations have been performed on negatively charged nitric
      acid-sulfuric acid-dimethylamine clusters. The cluster energies were combined
      with a kinetic model to study the chemical ionization of sulfuric acid molecules
      and sulfuric acid-dimethylamine clusters with nitrate ions. Both the sulfuric
      acid monomer and the H2SO4.(CH3)2NH cluster get ionized, but the cluster has a
      much higher dipole moment, and thus a higher collision rate with charger ions.
      Clustering of sulfuric acid with bases will therefore increase its detection
      probability in the CIMS, instead of decreasing it as has been suggested
      previously. However, our comparison of different quantum chemical methods shows
      some uncertainty on the extent of sulfuric acid-dimethylamine cluster formation
      in typical ambient conditions, and no experimental data is available for
      comparison. Apart from affecting CIMS measurements, the degree of clustering is
      directly linked to the formation rate of larger clusters, and needs to be
      quantified in order to understand atmospheric new-particle formation. On the
      basis of the different charging efficiencies of the monomer and the cluster, a
      method is proposed for determining experimentally the binding energies of
      H2SO4.base clusters by measuring the extent of cluster formation as a function of
      base concentration. 

PMID- 24295487
TI  - Management of HIV-associated tuberculosis in resource-limited settings: a state
      of-the-art review.
AB  - The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public
      health in resource-limited settings. Reducing the nearly 0.5 million deaths that
      result each year has been identified as a key priority. Major progress has been
      made over the past 10 years in defining appropriate strategies and policy
      guidelines for early diagnosis and effective case management. Ascertainment of
      cases has been improved through a twofold strategy of provider-initiated HIV
      testing and counseling in TB patients and intensified TB case finding among those
      living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced
      by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART
      reduces mortality across a spectrum of CD4 counts and randomized controlled
      trials have defined the optimum time to start ART. Good outcomes can be achieved
      when combining TB treatment with first-line ART, but use with second-line ART
      remains challenging due to pharmacokinetic drug interactions and cotoxicity. We
      review the frequency and spectrum of adverse drug reactions and immune
      reconstitution inflammatory syndrome (IRIS) resulting from combined treatment,
      and highlight the challenges of managing HIV-associated drug-resistant TB.

PMID- 24295490
TI  - In vitro and in vivo evaluations of a novel pulsed and controlled osmotic pump
      capsule.
AB  - OBJECTIVE: For better treatment of circadian cardiovascular events, a novel
      Propranolol hydrochloride (PNH) delayed-release osmotic pump capsule was
      developed. METHODS: The capsule body was designed of asymmetric membrane and the
      capsule cap was made impermeable. The physical characteristics of capsule body
      walls and membrane permeability were compared among different coating solutions.
      RESULTS: The formulation with the glycerin and diethyl phthalate (DEP) ratio of
      5:4 appeared to be the best. The lag time and subsequent drug release were
      investigated through assembling the capsule body with capsule caps of different
      length. WSR N-10 was chosen as the suspending for its moderate expanding
      capacity. The influence of factors (WSR N-10 content, NaCl content and capsule
      cap length) on the responses (lag time and drug release rate) was evaluated using
      central composite design-response surface methodology. A second-order polynomial
      equation was fitted to the data and actual response values were in good
      accordance with the predicted ones. The optimized formulation displayed complete
      drug delivery, zero-order release rate with 4-h lag time. The results of in vivo
      pharmacokinetics in beagle dogs clearly suggested the controlled and sustained
      release of PNH from the system and that the relative bioavailability of this
      preparation was about 1.023 comparing the marketed preparation. CONCLUSIONS:
      These results indicate that by the adjustment of capsule cap length, PNH could be
      developed as a novel pulsatile and controlled drug delivery system.

PMID- 24295491
TI  - Combinatorial synthesis of oxazol-thiazole bis-heterocyclic compounds.
AB  - A combinatorial library of novel oxazol-thiazole bis-heterocycles was synthesized
      in good to excellent overall yields with high purity using a solution and solid
      phase parallel synthesis approach. Oxazole amino acids, prepared from serine
      methyl ester and amino acids via coupling and cyclodehydration, were treated with
      Fmoc-NCS and alpha-haloketones for the parallel synthesis of diverse bis
      heterocycles. Fmoc-isothiocyanate is used as a traceless reagent for thiazole
      formation. Oxazole diversity can be achieved by using variety of amino acids,
      whereas thiazole diversity is produced with various haloketones. 

PMID- 24295492
TI  - DNA methylation and miRNAs regulation in hereditary breast cancer: epigenetic
      changes, players in transcriptional and post- transcriptional regulation in
      hereditary breast cancer.
AB  - The genetic alterations associated with breast carcinogenesis are well known. On
      the contrary epigenetic alterations in hereditary breast cancer are a new field.
      Two epigenetic mechanisms have emerged as the most critical players in
      transcriptional regulation in breast cancer: the methylation of DNA and microRNA
      interference. In this review we will focus on recent findings on gene silencing
      caused by DNA methylation and microRNA to explore the potential role of these
      epigenetic changes in the understanding of hereditary breast cancer. Moreover we
      will describe the same alterations in basal-like breast cancer and in triple
      negative breast cancer, since their phenotypes have similarities with BRCA1
      mutated tumors. To underline the possibility that some epigenetic alterations
      could also be used as potential epigenetic biomarkers of drug sensitivity or
      resistance, we will discuss the more common therapies in hereditary breast cancer
      that could also be applied to breast cancer with basal-like or triple negative
      phenotypes. 

PMID- 24295493
TI  - Id-1B, an alternatively spliced isoform of the inhibitor of differentiation-1,
      impairs cancer cell malignancy through inhibition of proliferation and
      angiogenesis.
AB  - Id-1 is a member of the helix-loop-helix family of proteins that regulates the
      activity of transcription factors to suppress cellular differentiation and to
      promote cell growth. Overexpression of Id-1 in tumor cells correlates with
      increased malignancy and resistance to chemotherapy and radiotherapy. Id-1B is an
      isoform generated by alternative splicing that differs from the classical Id-1 in
      the 13-C-terminal amino acids, whose function is at present unknown. We have
      studied the role of Id-1B in cancer and its expression in healthy/malignant lung
      tissues. Overexpression of Id-1B in A549 lung and PC3 prostate cancer cells
      reduced anchorage-dependent and independent proliferation and clonogenic
      potential. Moreover, it increased the proportion of cells in the G0/G1 phase of
      the cell cycle and p27 levels, while reduced phospho-Erk and cyclin A levels.
      Through microarray analysis, we identified genes involved in cell growth and
      proliferation that are specifically deregulated as a consequence of Id-1B
      overexpression, including IGF2, BMP4, Id2, GATA3, EREG and AREG. Id-1B
      overexpressing cells that were treated with 4Gy irradiation dose were
      significantly less resistant to cell death. In vivo assays demonstrated that
      tumors with high Id-1B levels exhibited less growth (p<0.01), metabolic activity
      (glucose uptake) and angiogenesis (p<0.05) compared to tumors with low Id-1B
      expression; mice survival was significantly extended (p<0.05). Quantification by
      qRT-PCR revealed that expression of Id-1B was significantly lower (p<0.01) in
      human lung tumors compared to their matched nonmalignant counterparts. In
      conclusion, our results demonstrate that Id-1B decreases the malignancy of lung
      and prostate cancer cells, sensitizes them to radiotherapy-induced cell death,
      and counteracts the protumorigenic role of the classical form of Id-1. 

PMID- 24295494
TI  - miR-221/222 confers radioresistance in glioblastoma cells through activating Akt
      independent of PTEN status.
AB  - Glioblastoma is highly resistant to radiation therapy. The underlying molecular
      mechanism is not completely understood. The DNA damage response (DDR) pathway
      plays a crucial role in radioresistance of glioablastoma cells. Growing evidence
      has demonstrated that radiation induces alterations in microRNA (miR) profiles.
      However, how radiation induces specific miRs and how they might regulate the DDR
      remain elusive. In our study, we found that radiation induced c-jun transcription
      of miR-221 and miR-222. miR-221 and miR- 222 modulated DNA-PKcs expression to
      affect DNA damage repair by activating Akt independent of PTEN status. Knocking
      down of miR-221/222 significantly increased radiosensitivity of glioblastoma
      cells. Inhibition of Akt by RNAi or LY294002 treatment may overcome miR-221/222
      induced radioresistance. Notably, combined anti-miR-221/222 and radiotherapy has
      remarkably inhibited tumor growth compared with anti-miR-221/222 or radiotherapy
      alone in a subcutaneous mouse model. Our results suggest that radio-induced c-jun
      promotes transcription of miR-221/222, which mediates DNA damage repair of
      glioblastoma cells independent of PTEN. These data indicate for the first time
      that miR-221/222 play an important role in mediating radio-induced DNA damage
      repair and that miR-221/222 could serve as potential therapeutic targets for
      increasing radiosensitivity of glioblastoma cells. 

PMID- 24295496
TI  - A novel executive function battery for preschoolers: Sensitivity to age
      differences.
AB  - The present study investigated sensitivity to age differences in a novel
      executive function (EF) battery for children aged 18 months to 5 years, and
      whether the pattern of associations among the measures was consistent with a
      hierarchical model of EF development. Participants (n = 261, aged 18-67 months)
      were administered a battery of novel tasks designed to assess 3 key EF components
      (working memory, inhibition, and shifting). The results indicate that the EF
      tasks were sensitive to age differences and provide partial support for the
      hierarchical model of EF development.

PMID- 24295497
TI  - The neurobiology of remote memory in the experimental animal.

PMID- 24295495
TI  - Secretory pathway of cellulase: a mini-review.
AB  - Cellulase plays an important role in modern industry and holds great potential in
      biofuel production. Many different types of organisms produce cellulase, which go
      through secretory pathways to reach the extracellular space, where enzymatic
      reactions take place. Secretory pathways in various cells have been the focus of
      many research fields; however, there are few studies on secretory pathways of
      cellulases in the literature. It is therefore necessary and important to review
      the current knowledge on the secretory pathways of cellulases. In this mini
      review, we address the subcellular locations of cellulases in different
      organisms, discuss the secretory pathways of cellulases in different organisms,
      and examine the secretory mechanisms of cellulases. These sections start with a
      description of general secreted proteins, advance to the situation of cellulases,
      and end with the knowledge of cellulases, as documented in UniProt Knowledgebase
      (UniProtKB). Finally, gaps in existing knowledge are highlighted, which may shed
      light on future studies for biofuel engineering. 

PMID- 24295498
TI  - DMF as carbon source: Rh-catalyzed alpha-methylation of ketones.
AB  - An unprecedented Rh-catalyzed direct methylation of ketones with N,N
      dimethylformamide (DMF) is disclosed. The reaction shows a broad substrate scope,
      tolerating both aryl and alkyl ketones with various substituents. Mechanistic
      studies suggest that DMF delivers a methylene fragment followed by a hydride in
      the methylation process. 

PMID- 24295500
TI  - Propolis organogel as a novel topical delivery system for treating wounds.
AB  - CONTEXT: Propolis has traditionally been used in curing infections and healing
      wounds and burns. OBJECTIVE: The aim of this study is to formulate pluronic
      lecithin organogel of propolis to improve its availability and antimicrobial
      activity. MATERIALS AND METHODS: Different organogels were prepared by using
      soybean lecithin, isopropyl palmitate, pluronic F127 and water. The effect of
      quantity of lecithin and pluronic F127 and percentage of oil phase was
      investigated. The organogels were evaluated for appearance, texture, pH, drug
      content and viscosity. In vitro release studies were carried out using cellophane
      membrane. Drug permeation through abdominal rat skin from organogels that showed
      high % drug release was compared to that from propolis suspension in distilled
      water. Finally, the antimicrobial activity of the selected propolis formulation
      against different bacterial isolates was compared with that of propolis
      suspension in water. RESULTS AND DISCUSSION: Results showed that all organogel
      formulations except the formula containing 10% pluronic F127, showed acceptable
      physical properties. Drug content of organogel formulations was in the range of
      97.5-100.2%. The pH of the formulations was in the range of 5.5-6.3 that suits
      the skin pH, indicating skin compatibility. The viscosity was in the range of
      5366-8984 cp. A significant decrease in drug release from formulations was
      observed with increase in concentration of lecithin and pluronic F127. Decreasing
      oil phase percentage to 20% w/w led to a decrease in drug release from the
      formulation. CONCLUSION: The formula containing 3% lecithin and 20% pluronic F127
      exhibited superior skin permeation and antimicrobial activity over propolis
      suspension in water.

PMID- 24295499
TI  - Functional consequences of a tissue-engineered myocardial patch for cardiac
      repair in a rat infarct model.
AB  - Cell therapies have emerged as a promising treatment for the prevention of heart
      failure after myocardial infarction (MI). This study evaluated the capacity of an
      aligned, fibrin-based, stretch-conditioned cardiac patch consisting of either the
      native population or a cardiomyocyte (CM)-depleted population (i.e., CM+ or CM-
      patches) of neonatal rat heart cells to ameliorate left ventricular (LV)
      remodeling in the acute-phase postinfarction in syngeneic, immunocompetent rats.
      Patches were exposed to 7 days of static culture and 7 days of cyclic stretching
      prior to implantation. Within 1 week of implantation, both patches became
      vascularized, and non-CMs began migrating from CM+ patches. By week 4, patches
      had been remodeled into collagenous tissue, and live, elongated, donor CMs were
      found within grafted CM+ patches. Significant improvement in cardiac contractile
      function was seen with the administration of the CM+ patch (ejection fraction
      increased from 35.1% +/- 4.0% for MI only to 58.8% +/- 7.3% with a CM+ patch,
      p<0.05) associated with a 77% reduction in infarct size (61.3% +/- 7.9% for MI
      only, 13.9% +/- 10.8% for CM+ patch, p<0.05), and the elimination of LV free-wall
      thinning. Decreased infarct size and reduced wall thinning also occurred with the
      administration of the CM- patch (infarct size 36.9% +/- 10.2%, LV wall thickness:
      1058.2 +/- 135.4 MUm for CM- patch, 661.3 +/- 37.4 MUm for MI only, p<0.05), but
      without improvements in cardiac function. Approximately 36.5% of the transplanted
      CMs survived at 4 weeks; however, they remained separated and electrically
      uncoupled from the host myocardium by a layer of CM-free tissue, which suggests
      that the benefits of CM+ patch transplantation resulted from paracrine mechanisms
      originating from CMs. Collectively, these observations suggest that the
      transplantation of CM-containing engineered heart tissue patches can lead to
      dramatic improvements in cardiac function and remodeling after acute MI.

PMID- 24295502
TI  - Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral
      hemorrhage.
AB  - Intracranial hemorrhage is the third most common cause of cerebrovascular
      disease. Some polymorphisms that affect clotting factors increase the risk of
      thrombosis. However, few reports have analyzed the effect of polymorphisms on the
      hemostatic state in bleeding disorders. The low-density lipoprotein receptor
      (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which
      represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the
      coagulation cascade. Patients with high levels of FVIII are at an increased risk
      of arterial and venous thrombosis. On the other hand, patients with insufficient
      FVIII tend to bleed excessively, such as in hemophilia A. In a previous study,
      analysis of the genetic LDLR variant rs688 provided evidence suggesting that
      genetic polymorphisms of rs688 are associated with thrombotic cardiovascular
      diseases. The current study aimed to investigate the potential role of rs688 in
      primary intracerebral hemorrhage (PICH). This genetic association study was
      conducted within an isolated Taiwanese population (447 PICH patients and 430
      controls). Genotypes C/C and C/T were used as the reference genotypes, and the
      genotype T/T was found to be associated with a 73% decreased risk of PICH. The
      preliminary evidence suggests that genetic polymorphisms of LDLR are associated
      with PICH. 

PMID- 24295501
TI  - Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope
      glycoprotein using evolutionary models.
AB  - BACKGROUND: Identification of the epitopes targeted by antibodies that can
      neutralize diverse HIV-1 strains can provide important clues for the design of a
      preventative vaccine. METHODS: We have developed a computational approach that
      can identify key amino acids within the HIV-1 envelope glycoprotein that
      influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence
      alignment and neutralization titers for a panel of viruses, the method works by
      fitting a phylogenetic model that allows the amino acid frequencies at each site
      to depend on neutralization sensitivities. Sites at which viral evolution
      influences neutralization sensitivity were identified using Bayes factors (BFs)
      to compare the fit of this model to that of a null model in which sequences
      evolved independently of antibody sensitivity. Conformational epitopes were
      identified with a Metropolis algorithm that searched for a cluster of sites with
      large Bayes factors on the tertiary structure of the viral envelope. RESULTS: We
      applied our method to ID50 neutralization data generated from seven HIV-1 subtype
      C serum samples with neutralization breadth that had been tested against a multi
      clade panel of 225 pseudoviruses for which envelope sequences were also
      available. For each sample, between two and four sites were identified that were
      strongly associated with neutralization sensitivity (2ln(BF) > 6), a subset of
      which were experimentally confirmed using site-directed mutagenesis. CONCLUSIONS:
      Our results provide strong support for the use of evolutionary models applied to
      cross-sectional viral neutralization data to identify the epitopes of serum
      antibodies that confer neutralization breadth.

PMID- 24295503
TI  - LINE-1 methylation is associated with an increased risk of ischemic stroke in
      men.
AB  - The level of global DNA methylation may be related to the cerebrovascular
      disease. The methylation level of Long Interspersed Nucleotide Element 1 (LINE-1)
      can represent the global methylation level. We investigated the association
      between the methylation levels of LINE-1 and ischemic stroke in Chinese. Two
      hundred and eighty patients of ischemic stroke and 280 age- and sex-matched
      controls were enrolled. The mean percentage of three CpG sites of LINE-1 was
      calculated for each subject and was used for analysis. Twenty four samples were
      re-checked for reproducibility of the methylation assay. Multivariate regression
      model was used to estimate the odds ratio of stroke risk for one percent change
      of methylation. Sex-specific analysis was also conducted. Thirty-two cases and 11
      controls did not pass the methylation assay criteria, and were excluded from
      further analysis. The intra-class correlation has a coefficient of 0.97 for the
      methylation assay. The stroke cases had a lower methylation level than controls
      (p=0.002), especially male subjects (p=0.001). Sex-specific analysis showed that
      a decrease of 1% methylation level in men could increase a stroke risk by 1.2
      fold after adjusting for other risk factors. LINE-1 methylation levels did not
      have a significant association with stroke in women. The present study shows that
      a lower level of LINE-1 methylation was associated with a higher risk for
      ischemic stroke in men, but methylation level in women did not affect the stroke
      risk. Our finding in Chinese is consistent with a previous result based on
      elderly white men. 

PMID- 24295504
TI  - Intranasal immunization of mice with inactivated virus and mast cell activator
      C48/80 elicits protective immunity against influenza H1 but not H5.
AB  - Vaccination represents the most economic and effective strategy of preventing
      influenza pandemics. We previously demonstrated that intranasal immunization of
      mice with recombinant hemagglutinin and the mast cell activator C48/80 elicited
      protective immunity against challenge with the 2009 pandemic H1N1 influenza in
      mice, demonstrating that the novel C48/80 mucosal adjuvant was safe and
      effective. The present study demonstrated that intranasal immunization with
      inactivated H1N1 virus and C48/80 elicited protective immunity against lethal
      challenge with homologous virus, however, when the immunogen was replaced with
      inactivated H5N1 virus protection was lost. These observations suggested that the
      adjuvant effects conferred by C48/80 were virus subtype specific and that its use
      as a broad-spectrum adjuvant for use in immunizations against all influenza
      viruses needs to be further analyzed. 

PMID- 24295505
TI  - Estimation of glomerular filtration rate from serum creatinine and cystatin C in
      octogenarians and nonagenarians.
AB  - BACKGROUND: Equations to estimate GFR have not been well validated in the elderly
      and may misclassify persons with chronic kidney disease (CKD). We measured GFR
      and compared the performance of the Modification of Diet in Renal Disease (MDRD),
      the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin
      Initiative Study (BIS) equations based on creatinine and/or cystatin C in
      octogenarians and nonagenarians. METHODS: Using cross-sectional analysis we
      assessed 95 very elderly persons (mean 85 years) living in the community. GFR was
      measured by iohexol (mGFR) and compared with estimates using six equations: MDRD,
      CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine
      and BIS_creatinine-cystatin. RESULTS: Mean mGFR was 55 (range,19-86) ml/min/1.73
      m(2). Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD
      Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m(2)). Accuracy (percentage of
      estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin,
      BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%,
      respectively). Among the creatinine-based equations, the BIS_creatinine had the
      greatest accuracy at mGFR < 60 ml/min/1.73 m(2) and the CKD-Epi_creatinine was
      superior at higher GFRs (79% and 90%, respectively). The CKD-Epi_creatinine
      cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the
      greatest areas under the receiver operating characteristic curve at GFR threshold
      = 60 ml/min/1.73 m 2 (0.88, 0.88 and 0.87, respectively). In participants
      classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine
      cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve
      CKD classification (net reclassification index: 12.7%, p = 0.18; 6.7%, p = 0.38;
      and 15.9%; p = 0.08, respectively). CONCLUSIONS: GFR-estimating equations CKD
      Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than
      other equations using creatinine or cystatin C alone in very elderly persons. The
      CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD
      classification. If cystatin C is not available, both the BIS_cr equation and the
      CKD-Epi_cr equation could be used, although at mGFR < 60 ml/min/1.73 m(2), the
      BIS_cr equation seems to be the best alternative.

PMID- 24295506
TI  - Association between vigor and exhaustion during the workweek: a person-centered
      approach to daily assessments.
AB  - The purpose of this quantitative diary study was to investigate daily vigor and
      exhaustion using a person-centered approach. The study also investigated whether
      and how experiences of vigor and exhaustion relate to a state of being recovered.
      A total of 256 Finnish employees filled in a diary questionnaire during five
      consecutive workdays. Vigor and exhaustion showed strong negative interdependence
      within and between days. However, by applying a person-centered analysis, we were
      able to differentiate three groups with meaningful variation in vigor and
      exhaustion. The groups were labeled as Constantly vigorous (n = 179),
      Concurrently vigorous and exhausted (n = 30) and Constantly exhausted (n = 43).
      The vigor-exhaustion groups were also characterized by their recovery
      experiences: The Constantly vigorous employees recovered well from work strain
      during the workweek whereas the Constantly exhausted group recovered poorly.
      Overall, while the results indicate that, typically, vigor and exhaustion are
      exclusive experiences, it is also possible for them to be experienced
      simultaneously from day to day at the moderate levels. Thus, positive and
      negative experiences may co-occur. 

PMID- 24295507
TI  - Examining the efficacy of a personalized normative feedback intervention to
      reduce college student gambling.
AB  - OBJECTIVE: To evaluate the efficacy of a stand-alone personalized normative
      feedback (PNF) intervention targeting misperceptions of gambling among college
      students. PARTICIPANTS: Undergraduates (N = 136; 55% male) who reported gambling
      in the past 30 days were recruited between September 2011 and March 2012.
      METHODS: Using a randomized clinical trial design, participants were assigned to
      receive either PNF or an attention control task. In addition to self-report, this
      study used 2 computer-based risk tasks framed as "gambling opportunities" to
      assess cognitive and behavioral change at 1 week post intervention. RESULTS:
      After 1 week, participants receiving PNF showed a marked decrease in perception
      of other students' gambling, and evinced lower risk-taking performance on 2
      analog measures of gambling. CONCLUSIONS: Changes in both self-reported perceived
      norms and analog gambling behavior suggest that a single, stand-alone PNF
      intervention may modify gambling among college students. Whether it can impact
      gambling outside of the laboratory remains untested.

PMID- 24295508
TI  - The effects of hyperlipidemia on implant osseointegration in the mouse femur.
AB  - A high-fat (HF) diet inducing hyperlipidemia has been associated with the
      pathophysiology of major diseases, such as atherosclerosis and osteoporosis. A HF
      diet has significant adverse effects on bone, including lower bone density,
      volume, and strength. Statins, drugs that lower serum cholesterol levels have
      beneficial effects on bone metabolism. Since the host's bone quantity, quality,
      and healing potential play a crucial role in osseointegration of dental implants,
      we hypothesized that hyperlipidemia may negatively affect implant
      osseointegration. In the present study, we evaluated the effects of
      hyperlipidemia on implant osseointegration in mice. Atherosclerosis susceptible
      C57BL/6J male mice were randomly placed on a control chow or a HF diet. After 12
      weeks on the diet, each mouse received a titanium implant in the proximal
      metaphysis of the femur. The animals were humanely killed at 4 or 8 weeks after
      the implant surgery. Results showed that the mice fed a HF diet had significantly
      increased implant loss as well as decreased formation and strength of bone-to
      implant interface. These results support the hypothesis that a HF diet can
      significantly compromise osseointegration, causing poor outcome in dental implant
      therapy. 

PMID- 24295510
TI  - Catalytic stereoselective synthesis of beta-digitoxosides: direct synthesis of
      digitoxin and C1'-epi-digitoxin.
AB  - A mild and atom-economic rhenium(V)-catalyzed stereoselective synthesis of beta-D
      digitoxosides from 6-deoxy-D-allals has been described. This beta-selective
      glycosylation was achieved probably because of the formation of corresponding
      alpha-digitoxosides disfavored by 1,3-diaxial interaction. In addition, this
      method has been successfully applied to the synthesis of digitoxin trisaccharide
      glycal for the direct synthesis of digitoxin and C1'-epi-digitoxin.

PMID- 24295509
TI  - Development of clinical decision rules to predict recurrent shock in dengue.
AB  - INTRODUCTION: Mortality from dengue infection is mostly due to shock. Among
      dengue patients with shock, approximately 30% have recurrent shock that requires
      a treatment change. Here, we report development of a clinical rule for use during
      a patient's first shock episode to predict a recurrent shock episode. METHODS:
      The study was conducted in Center for Preventive Medicine in Vinh Long province
      and the Children's Hospital No. 2 in Ho Chi Minh City, Vietnam. We included 444
      dengue patients with shock, 126 of whom had recurrent shock (28%). Univariate and
      multivariate analyses and a preprocessing method were used to evaluate and select
      14 clinical and laboratory signs recorded at shock onset. Five variables
      (admission day, purpura/ecchymosis, ascites/pleural effusion, blood platelet
      count and pulse pressure) were finally trained and validated by a 10-fold
      validation strategy with 10 times of repetition, using a logistic regression
      model. RESULTS: The results showed that shorter admission day (fewer days prior
      to admission), purpura/ecchymosis, ascites/pleural effusion, low platelet count
      and narrow pulse pressure were independently associated with recurrent shock. Our
      logistic prediction model was capable of predicting recurrent shock when compared
      to the null method (P < 0.05) and was not outperformed by other prediction
      models. Our final scoring rule provided relatively good accuracy (AUC, 0.73;
      sensitivity and specificity, 68%). Score points derived from the logistic
      prediction model revealed identical accuracy with AUCs at 0.73. Using a cutoff
      value greater than -154.5, our simple scoring rule showed a sensitivity of 68.3%
      and a specificity of 68.2%. CONCLUSIONS: Our simple clinical rule is not to
      replace clinical judgment, but to help clinicians predict recurrent shock during
      a patient's first dengue shock episode.

PMID- 24295511
TI  - A reverse micellar mesophase of face-centered cubic Fm3m symmetry in
      phosphatidylcholine/water/organic solvent ternary systems.
AB  - We report the formation of a reverse micellar cubic mesophase of symmetry Fm3m
      (Q(225)) in ternary mixtures of soy bean phosphatidylcholine (PC), water, and an
      organic solvent, including cyclohexane, (R)-(+)-limonene, and isooctane, studied
      by small-angle X-ray scattering (SAXS) and oscillatory shear rheology at room
      temperature. The mesophase structure consists of a compact packing of remarkably
      large reverse micelles in a face-centered cubic (fcc) lattice, a type of micellar
      packing not yet reported for reverse micellar mesophases. Form factor fitting in
      the pure L2 phase and in the Fm3m-L2 coexistence region yields quantitative
      estimations of the PC interface rigidity. The compact Fm3m structure results
      mainly from release of lipid tail frustration and hard-sphere interactions
      between monodisperse micelles, as suggested by a comparison with the Fd3m
      structure found in the PC/water/alpha-tocopherol system.

PMID- 24295513
TI  - Cognate effects in sentence context depend on word class, L2 proficiency, and
      task.
AB  - Noun translation equivalents that share orthographic and semantic features,
      called "cognates", are generally recognized faster than translation equivalents
      without such overlap. This cognate effect, which has also been obtained when
      cognates and noncognates were embedded in a sentence context, emerges from the
      coactivation of representations in two languages. The present study examined
      whether cognate facilitation in sentences is subject to effects of word class,
      reading proficiency in a second language (L2), and task demands. We measured eye
      movements (Experiment 1) and self-paced reading times (Experiment 2) for Dutch
      English bilinguals reading L2 sentences that contained either a noun or a verb
      cognate. Results showed that cognate effects were smaller for verbs than for
      nouns. Furthermore, cognate facilitation was reduced for readers with a higher
      proficiency in L2 as expressed by self-ratings or reading speed in L2.
      Additionally, the results of the eye-movement study and the self-paced reading
      study indicated that the likelihood of observing cognate facilitation effects
      also depends on task demands. The obtained pattern of results helps to identify
      some of the boundaries of the cognate effect. 

PMID- 24295512
TI  - Three-dimensional printed multiphase scaffolds for regeneration of periodontium
      complex.
AB  - Tooth-supporting periodontium forms a complex with multiple tissues, including
      cementum, periodontal ligament (PDL), and alveolar bone. In this study, we
      developed multiphase region-specific microscaffolds with spatiotemporal delivery
      of bioactive cues for integrated periodontium regeneration. Polycarprolactione
      hydroxylapatite (90:10 wt%) scaffolds were fabricated using three-dimensional
      printing seamlessly in three phases: 100-MUm microchannels in Phase A designed
      for cementum/dentin interface, 600-MUm microchannels in Phase B designed for the
      PDL, and 300-MUm microchannels in Phase C designed for alveolar bone. Recombinant
      human amelogenin, connective tissue growth factor, and bone morphogenetic protein
      2 were spatially delivered and time-released in Phases A, B, and C, respectively.
      Upon 4-week in vitro incubation separately with dental pulp stem/progenitor cells
      (DPSCs), PDL stem/progenitor cells (PDLSCs), or alveolar bone stem/progenitor
      cells (ABSCs), distinctive tissue phenotypes were formed with collagen I-rich
      fibers especially by PDLSCs and mineralized tissues by DPSCs, PDLSCs, and ABSCs.
      DPSC-seeded multiphase scaffolds upon in vivo implantation yielded aligned PDL
      like collagen fibers that inserted into bone sialoprotein-positive bone-like
      tissue and putative cementum matrix protein 1-positive/dentin sialophosphoprotein
      positive dentin/cementum tissues. These findings illustrate a strategy for the
      regeneration of multiphase periodontal tissues by spatiotemporal delivery of
      multiple proteins. A single stem/progenitor cell population appears to
      differentiate into putative dentin/cementum, PDL, and alveolar bone complex by
      scaffold's biophysical properties and spatially released bioactive cues.

PMID- 24295514
TI  - Molecular investigation of the 7.2 kb RNA of murine cytomegalovirus.
AB  - BACKGROUND: HCMV encodes a stable 5 kb RNA of unknown function that is conserved
      across cytomegalovirus species. In vivo studies of the MCMV orthologue, a 7.2 kb
      RNA, demonstrated that viruses that do not express the RNA fail to establish
      efficient persistent replication in the salivary glands of mice. To gain further
      insight into the function and properties of this conserved locus, we
      characterized the MCMV intron in finer detail. METHODS: We performed multiple
      analyses to evaluate transcript expression kinetics, identify transcript termini
      and promoter elements. The half-lives of intron locus RNAs were quantified by
      measuring RNA levels following actinomycin D treatment in a qRT-PCR-based assay.
      We also constructed a series of recombinant viruses to evaluate protein coding
      potential in the locus and test the role of putative promoter elements. These
      recombinant viruses were tested in both in vitro and in vivo assays. RESULTS: We
      show that the 7.2 kb RNA is expressed with late kinetics during productive
      infection of mouse fibroblasts. The termini of the precursor RNA that is
      processed to produce the intron were identified and we demonstrate that the m106
      open reading frame, which resides on the spliced mRNA derived from precursor
      processing, can be translated during infection. Mapping the 5' end of the primary
      transcript revealed minimal promoter elements located upstream that contribute to
      transcript expression. Analysis of recombinant viruses with deletions in the
      putative promoter elements, however, revealed these elements exert only minor
      effects on intron expression and viral persistence in vivo. Low transcriptional
      output by the putative promoter element(s) is compensated by the long half-life
      of the 7.2 kb RNA of approximately 28.8 hours. Detailed analysis of viral spread
      prior to the establishment of persistence also showed that the intron is not
      likely required for efficient spread to the salivary gland, but rather enhances
      persistent replication in this tissue site. CONCLUSIONS: This data provides a
      comprehensive transcriptional analysis of the MCMV 7.2 kb intron locus. Our
      studies indicate that the 7.2 kb RNA is an extremely long-lived RNA, a feature
      which is likely to be important in its role promoting viral persistence in the
      salivary gland.

PMID- 24295515
TI  - The benefits of playing video games.
AB  - Video games are a ubiquitous part of almost all children's and adolescents'
      lives, with 97% playing for at least one hour per day in the United States. The
      vast majority of research by psychologists on the effects of "gaming" has been on
      its negative impact: the potential harm related to violence, addiction, and
      depression. We recognize the value of that research; however, we argue that a
      more balanced perspective is needed, one that considers not only the possible
      negative effects but also the benefits of playing these games. Considering these
      potential benefits is important, in part, because the nature of these games has
      changed dramatically in the last decade, becoming increasingly complex, diverse,
      realistic, and social in nature. A small but significant body of research has
      begun to emerge, mostly in the last five years, documenting these benefits. In
      this article, we summarize the research on the positive effects of playing video
      games, focusing on four main domains: cognitive, motivational, emotional, and
      social. By integrating insights from developmental, positive, and social
      psychology, as well as media psychology, we propose some candidate mechanisms by
      which playing video games may foster real-world psychosocial benefits. Our aim is
      to provide strong enough evidence and a theoretical rationale to inspire new
      programs of research on the largely unexplored mental health benefits of gaming.
      Finally, we end with a call to intervention researchers and practitioners to test
      the positive uses of video games, and we suggest several promising directions for
      doing so.

PMID- 24295516
TI  - Development of a forward genetic screen to isolate oil mutants in the green
      microalga Chlamydomonas reinhardtii.
AB  - BACKGROUND: Oils produced by microalgae are precursors to biodiesel. To achieve a
      profitable production of biodiesel from microalgae, identification of factors
      governing oil synthesis and turnover is desirable. The green microalga
      Chlamydomonas reinhardtii is amenable to genetic analyses and has recently
      emerged as a model to study oil metabolism. However, a detailed method to isolate
      various types of oil mutants that is adapted to Chlamydomonas has not been
      reported. RESULTS: We describe here a forward genetic approach to isolate mutants
      altered in oil synthesis and turnover from C. reinhardtii. It consists of a three
      step screening procedure: a primary screen by flow cytometry of Nile red stained
      transformants grown in 96-deep-well plates under three sequential conditions
      (presence of nitrogen, then absence of nitrogen, followed by oil remobilization);
      a confirmation step using Nile red stained biological triplicates; and a
      validation step consisting of the quantification by thin layer chromatography of
      oil content of selected strains. Thirty-one mutants were isolated by screening
      1,800 transformants generated by random insertional mutagenesis (1.7%). Five
      showed increased oil accumulation under the nitrogen-replete condition and 13 had
      altered oil content under nitrogen-depletion. All mutants were affected in oil
      remobilization. CONCLUSION: This study demonstrates that various types of oil
      mutants can be isolated in Chlamydomonas based on the method set-up here,
      including mutants accumulating oil under optimal biomass growth. The strategy
      conceived and the protocol set-up should be applicable to other microalgal
      species such as Nannochloropsis and Chlorella, thus serving as a useful tool in
      Chlamydomonas oil research and algal biotechnology.

PMID- 24295517
TI  - HLA-DRB1* association with sarcoidosis.

PMID- 24295518
TI  - Statistical mixture design and multivariate analysis of inkjet printed a
      WO3/TiO2/WOX electrochromic films.
AB  - An efficient mathematical strategy in the field of solution processed
      electrochromic (EC) films is outlined as a combination of an experimental work,
      modeling, and information extraction from massive computational data via
      statistical software. Design of Experiment (DOE) was used for statistical
      multivariate analysis and prediction of mixtures through a multiple regression
      model, as well as the optimization of a five-component sol-gel precursor
      subjected to complex constraints. This approach significantly reduces the number
      of experiments to be realized, from 162 in the full factorial (L=3) and 72 in the
      extreme vertices (D=2) approach down to only 30 runs, while still maintaining a
      high accuracy of the analysis. By carrying out a finite number of experiments,
      the empirical modeling in this study shows reasonably good prediction ability in
      terms of the overall EC performance. An optimized ink formulation was employed in
      a prototype of a passive EC matrix fabricated in order to test and trial this
      optically active material system together with a solid-state electrolyte for the
      prospective application in EC displays. Coupling of DOE with chromogenic material
      formulation shows the potential to maximize the capabilities of these systems and
      ensures increased productivity in many potential solution-processed
      electrochemical applications.

PMID- 24295520
TI  - Overexpression of CD38 decreases cellular NAD levels and alters the expression of
      proteins involved in energy metabolism and antioxidant defense.
AB  - Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells
      and mediates multiple cellular signaling pathways. In the present study, a 35%
      decrease of cellular NAD level is achieved by stable expression of the N-terminal
      truncated CD38, a NAD hydrolase. CD38-expressing (CD38(+)) cells have the lower
      growth rate and are more susceptive to oxidative stress than the wild type cells
      and empty vector-transfected (CD38(-)) cells. Quantitative proteomic analysis
      shows that 178 proteins are down-regulated in CD38(+) cells, which involve in
      diverse cellular processes including glycolysis, RNA processing and protein
      synthesis, antioxidant, and DNA repair. Down regulation of six selected proteins
      is confirmed by Western blotting. However, down-regulation of mRNA expressions of
      genes associated with glycolysis, antioxidant, and DNA repair is less significant
      than the corresponding change in protein expression, suggesting the low NAD level
      impairs the protein translational machinery in CD38(+) cells. Down-regulation of
      antioxidant protein and DNA-repair protein expression contributes to the
      susceptibility of CD38(+) cells to oxidative stress. Taken together, these
      results demonstrate that CD38(+) cells are a useful model to study effects of the
      cellular NAD levels on cellular processes and establish a new linker between
      cellular NAD levels and oxidative stress. 

PMID- 24295521
TI  - The presence and role of iron in mild traumatic brain injury: an imaging
      perspective.
AB  - Mild traumatic brain injury (mTBI), although often presenting without the gross
      structural abnormalities seen in more severe forms of brain trauma, can
      nonetheless result in lingering cognitive and behavioral problems along with
      subtle alterations in brain structure and function. Repeated injuries are
      associated with brain atrophy and dementia in the form of chronic traumatic
      encephalopathy (CTE). The mechanisms underlying these dysfunctions are poorly
      understood. There is a growing body of evidence that brain iron is abnormal after
      TBI, and brain iron has also been implicated in a host of neurodegenerative
      disorders. The purpose of this article is to review evidence about the function
      of iron in the pathophysiology of mTBI and the role that advanced imaging
      modalities can play in further elucidating said function. MRI techniques
      sensitive to field inhomogeneities provide supporting evidence for both deep gray
      matter non-heme iron accumulation as well as focal microhemorrhage resulting from
      mTBI. In addition, there is evidence that iron may contribute to pathology after
      mTBI through a number of mechanisms, including generation of reactive oxygen
      species (ROS), exacerbation of oxidative stress from other sources, and
      encouragement of tau phosphorylation and the formation of neurofibrillary
      tangles. Finally, recent animal studies suggest that iron may serve as a
      therapeutic target in mitigating the effects of mTBI. However, research on the
      presence and role of iron in mTBI and CTE is still relatively sparse, and further
      work is necessary to elucidate issues such as the sources of increased iron and
      the chain of secondary injury.

PMID- 24295523
TI  - Eliciting change in at-risk elders (ECARE): evaluation of an elder abuse
      intervention program.
AB  - The current study evaluated the effectiveness of a community-based elder abuse
      intervention program that assists suspected victims of elder abuse and self
      neglect through a partnership with local law enforcement. This program, Eliciting
      Change in At-Risk Elders, involves building alliances with the elder and family
      members, connecting the elder to supportive services that reduce risk of further
      abuse, and utilizing motivational interviewing-type skills to help elders
      overcome ambivalence regarding making difficult life changes. Risk factors of
      elder abuse decreased over the course of the intervention and nearly three
      quarters of participants made progress on their treatment goal, advancing at
      least one of Prochaska and DiClemente's (1983) stages of change
      (precontemplation, contemplation, preparation, action, and maintenance). Forty
      three percent of elders moved into the stages of action and maintenance regarding
      their goal. The usefulness of eliciting change via longer-term relationships with
      vulnerable elders in entrenched elder abuse situations is discussed. 

PMID- 24295522
TI  - Fluid overload in hemodialysis patients: a cross-sectional study to determine its
      association with cardiac biomarkers and nutritional status.
AB  - BACKGROUND: Chronic fluid overload is associated with higher mortality in
      dialysis patients; however, the link with cardiovascular morbidity has not
      formally been established and may be influenced by subclinical inflammation. We
      hypothesized that a relationship exists between fluid overload and [i]
      cardiovascular laboratory parameter as well as between fluid overload and [ii]
      inflammatory laboratory parameters. In addition, we aimed to confirm whether
      volume status correlates with nutritional status. METHODS: We recorded baseline
      characteristics of 244 hemodialysis patients at three hemodialysis facilities in
      Vienna (Austria) and determined associations with volume measurements using the
      body composition monitor (Fresenius/Germany). In one facility comprising 126
      patients, we further analyzed cardiovascular, inflammatory and nutritional
      parameters. RESULTS: We detected predialysis fluid overload (FO) in 39% of all
      patients (n = 95) with FO defined as >=15% of extracellular water (ECW). In this
      subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 +/- 4.8% of ECW. A sub
      analysis of patients from one center showed that FO was negatively associated
      with body mass index (r = -0.371; p = <0.001), while serum albumin was
      significantly lower in fluid overloaded patients (p = 0.001). FO was positively
      associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p <
      0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but
      not with investigated inflammatory parameters. CONCLUSIONS: Fluid overload in HD
      patients was found to be lower in patients with high body mass index, indicating
      that dry weight was inadequately prescribed and/or difficult to achieve in
      overweight patients. The association with parameters of cardiovascular compromise
      and/or damage suggests that fluid overload is a biomarker for cardiovascular
      risk. Future studies should determine if this applies to patients prior to end
      stage renal disease.

PMID- 24295524
TI  - Worldwide practices for pharmacologic therapy in esophageal variceal hemorrhage.
AB  - OBJECTIVE: Pharmacologic therapy (PT) for patients with esophageal variceal
      hemorrhage (EVH) may improve outcomes. The aim of this article is to assess the
      current and potential future use of PT in cirrhotic patients with EVH. MATERIAL
      AND METHODS: We validated a 13-question survey about PT and physician preferences
      for specific therapies in cirrhotics with EVH; 2349 randomly selected
      Gastroenterology and Hepatology physicians worldwide were surveyed. The survey
      addressed institutional location, octreotide or terlipressin use and preference,
      PT prior to endoscopy, and future plans for terlipressin use, if not already
      instituted. RESULTS: Of those surveyed, 337 (14%) email addresses were
      nonfunctioning. Of the remaining 2012 surveyed, 371 (18%) responses were
      collected. Nearly two-thirds of physicians preferred to use PT prior to
      endoscopic intervention (p < 0.001). Nearly 70% of respondents only had
      octreotide available, while 6% had only terlipressin. Of the 24% having both
      octreotide and terlipressin available, 55% preferred terlipressin compared to 38%
      who preferred octreotide (p < 0.001). Of those physicians currently not using
      terlipressin because of its unavailability, 93% would be willing to use it if it
      were readily available. CONCLUSIONS: Of physicians with both terlipressin and
      octreotide available for treatment of EVH in cirrhotics, most prefer
      terlipressin, even if currently unavailable.

PMID- 24295525
TI  - Meaning in life: an important factor for the psychological well-being of
      chronically ill patients?
AB  - PURPOSE: This study aimed to investigate 2 dimensions of meaning in life-
      Presence of Meaning (i.e., the perception of your life as significant,
      purposeful, and valuable) and Search for Meaning (i.e., the strength, intensity,
      and activity of people's efforts to establish or increase their understanding of
      the meaning in their lives)--and their role for the well-being of chronically ill
      patients. RESEARCH DESIGN: A sample of 481 chronically ill patients (M = 50
      years, SD = 7.26) completed measures on meaning in life, life satisfaction,
      optimism, and acceptance. We hypothesized that Presence of Meaning and Search for
      Meaning will have specific relations with all 3 aspects of well-being. RESULTS:
      Cluster analysis was used to examine meaning in life profiles. RESULTS supported
      4 distinguishable profiles (High Presence High Search, Low Presence High Search,
      High Presence Low Search, and Low Presence Low Search) with specific patterns in
      relation to well-being and acceptance. Specifically, the 2 profiles in which
      meaning is present showed higher levels of well-being and acceptance, whereas the
      profiles in which meaning is absent are characterized by lower levels.
      Furthermore, the results provided some clarification on the nature of the Search
      for Meaning process by distinguishing between adaptive (the High Presence High
      Search cluster) and maladaptive (the Low Presence High Search cluster) searching
      for meaning in life. CONCLUSIONS: The present study provides an initial glimpse
      in how meaning in life may be related to the well-being of chronically ill
      patients and the acceptance of their condition. Clinical implications are
      discussed.

PMID- 24295526
TI  - Upper extremity lymphedema: presence and effect on functioning five years after
      breast cancer treatment.
AB  - PURPOSE/OBJECTIVE: Our goal was to explore the effects of lymphedema on long-term
      adjustment among breast cancer survivors, in terms of functioning in important
      life environments. RESEARCH METHOD/DESIGN: Limb volume measurements and
      psychosocial survey data were collected from women shortly after undergoing
      surgical intervention for breast cancer and annually thereafter. A subset of
      these women were selected for the current study because they had preoperative
      limb volume measurement data, which is best suited to determine presence and
      severity of lymphedema. Our final sample of 61 women had both the arm
      measurements (preoperative and 5-year) and survey data (baseline and 5-year)
      needed for this study, which comprises a secondary cross-sectional analysis of
      longitudinal data. A correlational approach was used to explore associations
      among lymphedema (presence, severity, and whether the participant met the
      criteria for lymphedema at any assessment point since their treatment for breast
      cancer) and outcome variables (physical functioning, vocational functioning,
      social functioning, domestic functioning, and sexual functioning). RESULTS: Each
      of the three measures of lymphedema was significantly correlated with domestic
      functioning, but not with functioning in other common environments.
      CONCLUSIONS/IMPLICATIONS: Long-term breast cancer survivors are at risk for
      developing secondary conditions, such as lymphedema, to which they must learn to
      adjust and adapt. Lymphedema may increase risk for compromised functioning in
      everyday environments, a problem which lies at the heart of rehabilitation.
      Breast cancer survivorship, therefore, fits well within the scope of a
      rehabilitation framework.

PMID- 24295527
TI  - Rehabilitation following surgery: clinical and psychological predictors of
      activity limitations.
AB  - PURPOSE/OBJECTIVE: Activity limitations following surgery are common, and
      patients may have an extended period of pain and rehabilitation. Inguinal hernia
      surgery is a common elective procedure. This study incorporated fear-avoidance
      models in investigating cognitive and emotional variables as potential risk
      factors for activity limitations 4 months after inguinal hernia surgery. METHOD:
      This was a prospective cohort study, predicting activity limitations 4 months
      postoperatively (Time 3 [T3]) from measures taken before surgery (Time 1, [T1])
      and 1 week after surgery (Time 2 [T2]). The sample size at T1 was 135; response
      rates were 89% and 84% at T2 and T3 respectively. Questionnaires included
      measures of catastrophizing, fear of movement, depression, anxiety, optimism,
      perceived control over pain, pain, and activity limitations. Biomedical and
      surgical variables were recorded. Predictors of T3 activity limitations from T1
      and T2 were examined in hierarchical multiple regression equations. RESULTS: Over
      half of participants (57.7%) reported activity limitations due to their hernia at
      4 months post-surgery. Higher activity limitation levels were significantly
      predicted by older age, higher preoperative activity limitations, higher
      preoperative anxiety, and more severe postoperative pain and depression scores.
      CONCLUSIONS/IMPLICATIONS: Interventions to reduce preoperative anxiety and
      postoperative depression may lead to reduced 4-month activity limitations.
      However, the additional variance explained by psychological variables was low
      (DeltaR2 = 0.05). Our models, which included biomedical and surgical variables,
      accounted for less than 50% of the variance in activity limitations overall.
      Therefore, further investigation of psychological variables, particularly
      cognitions related specifically to activity behavior, would be merited.

PMID- 24295528
TI  - Managing lapses in cardiac rehabilitation exercise therapy: examination of the
      problem-solving process.
AB  - PURPOSE/OBJECTIVE: Poor adherence to cardiac rehabilitation (CR) exercise therapy
      is an ongoing problem. Problem-solving (PS) is an identified cognitive-behavioral
      strategy to promote exercise adherence. However, PS process has not been
      examined, and how PS promotes adherence is not known. Using Social Cognitive
      Theory and Ewart's Social Problem-Solving Model as guiding frameworks, we
      examined proposed theoretical links between persistence, an indicator of
      adherence, and (a) PS effectiveness and (b) self-regulatory efficacy. Based on
      the Model of Social Problem-Solving, 2 distinct components of the PS process
      (problem-solving and solution implementation), were examined. RESEARCH
      METHOD/DESIGN: Older adult participants (N = 52; 32 men) representing a typical
      CR sample (mean age = 65.6 years; SD = 10.8) participated in this correlational,
      observational study. RESULTS: Two hierarchical multiple regressions indicated
      that PS effectiveness and self-regulatory efficacy were significant predictors of
      anticipated persistence. Relative to PS process, both predictors accounted for:
      (a) 41% of the variance in anticipated persistence with PS; and (b) 49% of the
      variance in anticipated persistence with solution implementation.
      CONCLUSIONS/IMPLICATIONS: Proposed theoretical relationships were supported, and
      both PS effectiveness and self-regulatory efficacy accounted for a greater amount
      of the variance in anticipated persistence than either alone. Future efforts to
      improve adherence to rehabilitative exercise could include the use of PS. The 2
      distinct components of the PS process may be important for successful adjustment
      to problems.

PMID- 24295529
TI  - Factor analysis of the Spanish Multidimensional Attitudes Scale Toward Persons
      with Disabilities.
AB  - PURPOSE/OBJECTIVE: To study the psychometric properties of a Spanish version of
      the Multidimensional Attitudes Scale toward Persons with Disabilities (MAS) and
      examine its factor structure using confirmatory and exploratory factor analyses
      on data from a Colombian collegiate sample. RESEARCH METHOD/DESIGN: Five hundred
      students from Sur Colombia University in Neiva, Colombia, completed the
      Multidimensional Attitudes toward People with Disability scale. Forty-eight
      percent were male, and the average age for the entire sample was 21.25 years (SD
      = 3.50). Ninety-eight percent were undergraduates, 23% of whom were business
      majors and 33% of whom were education majors. RESULTS: An exploratory factor
      analysis (EFA) of data from half of participants suggested the retention of 4
      factors and the deletion of 4 items. A confirmatory factor analysis (CFA) on the
      data from the second half of participants using the 30 retained items and 4
      factor structure suggested that the 4-factor model fit adequately with the
      remaining 30 items. High internal consistency was found for the overall scale
      (alpha = .77, .78) and for the 4 resulting subscales: Affect (alpha = .88, .87),
      Cognition (alpha = .92, .90), Behavior (alpha = .88, .88), and Calm (alpha = .90,
      .89). CONCLUSIONS/IMPLICATIONS: This study modified the MAS to assess attitudes
      toward persons with disabilities in Colombia. The adequate reliability and fit of
      the factor structure of the Spanish MAS suggests that it holds promise to help
      researchers investigate attitudes toward persons with disabilities in Latin
      America, an important topic to the global disability community.

PMID- 24295530
TI  - Efficacy of a powered wheelchair simulator for school aged children: a randomized
      controlled trial.
AB  - PURPOSE: To determine the efficacy of a custom-made wheelchair simulation in
      training children to use a powered wheelchair (PWC). DESIGN: Randomized
      controlled trial employing the 4C/ID-model of learning. Twenty-eight typically
      developing children (13M, 15F; mean age 6 years, SD 6 months) were assessed on
      their operation of a PWC using a functional evaluation rating scale. Participants
      were randomly assigned to intervention (8 * 30-minute training sessions using a
      joystick operated wheelchair simulation) or control conditions (no task), and
      were reassessed on their PWC use after the intervention phase. Additional data
      from the simulation on completion times, errors, and total scores were recorded
      for the intervention group. RESULTS: Analysis of variance showed a main effect of
      time, with planned comparisons revealing a statistically significant change in
      PWC use for the intervention (p = .022) but not the control condition. Although
      the intervention group showed greater improvement than the controls, this did not
      reach statistical significance. Multiple regression analyses showed that gender
      was predictive of pretest (p = .005) functional ability. IMPLICATIONS: A
      simulated wheelchair task appears to be effective in helping children learn to
      operate a PWC. Greater attention should be given to female learners who
      underperformed when compared with their male counterparts. This low-cost
      intervention could be easily used at home to reduce PWC training times in
      children with motor disorders.

PMID- 24295531
TI  - Anxiety as a primary predictor of functional impairment after acquired brain
      injury: a brief report.
AB  - OBJECTIVE: Cognitive and emotional symptoms are primary causes of long-term
      functional impairment after acquired brain injury (ABI). Although the occurrence
      of post-ABI emotional difficulties is well-documented, most investigators have
      focused on the impact of depression on functioning after ABI, with few examining
      the role of anxiety. Knowledge of the latter's impact is essential for optimal
      treatment planning in neurorehabilitation settings. The purpose of the present
      study is therefore to examine the predictive relationships between cognition,
      anxiety, and functional impairment in an ABI sample. METHOD: Multiple regression
      analyses were conducted with a sample of 54 outpatients with ABI. Predictors
      selected from an archival data set included standardized neuropsychological
      measures and Beck Anxiety Inventory scores. Dependent variables were caregiver
      ratings of functional impairments in the Affective/Behavioral, Cognitive, and
      Physical/Dependency domains. RESULTS: Anxiety predicted a significant proportion
      of the variance in caregiver-assessed real-life affective/behavioral and
      cognitive functioning. In contrast, objective neuropsychological test scores did
      not contribute to the variance in functional impairment. Neither anxiety nor
      neuropsychological test scores significantly predicted impairment in everyday
      physical/dependency function. CONCLUSION: These findings support the role of
      anxiety in influencing functional outcome post-ABI and suggest the necessity of
      addressing symptoms of anxiety as an essential component of treatment in
      outpatient neurorehabilitation.

PMID- 24295532
TI  - I2/O2-promoted domino reactions of isatins or 3-hydroxyindolin-2-one derivatives
      with enaminones.
AB  - I2-promoted domino reactions of isatins or 3-hydroxyindolin-2-one derivatives
      with enaminones under O2 conditions have been established. The reactions of
      isatins with enaminones afforded functionalized tetracyclic pyrrolo[2,3,4
      kl]acridine derivatives in moderate to good yields through domino cyclization and
      C-H oxidation. The reactions of 3-hydroxyindolin-2-one derivatives with
      enaminones proceeded well to give functionalized pyrrolo[2,3,4-kl]acridine
      derivatives via tandem ring-opening/recyclization/methyl migration sequences with
      two C-C bonds cleaved. 

PMID- 24295533
TI  - Can conflict be energizing? a study of task conflict, positive emotions, and job
      satisfaction.
AB  - Scholars have assumed that the presence of negative emotions during task conflict
      implies the absence of positive emotions. However, emotions researchers have
      shown that positive and negative emotions are not 2 ends of a bipolar continuum;
      rather, they represent 2 separate, orthogonal dimensions. Drawing on affective
      events theory, we develop and test hypotheses about the effects of task conflict
      on positive emotions and job satisfaction. To this end, we distinguish among the
      frequency, intensity, and information gained from task conflict. Using field data
      from 232 employees in a long-term health care organization, we find that more
      frequent mild task conflict expression engenders more information acquisition,
      but more frequent intense task conflict expression hinders it. Because of the
      information gains from mild task conflict expression, employees feel more active,
      energized, interested, and excited, and these positive active emotions increase
      job satisfaction. The information gained during task conflict, however, is not
      always energizing: It depends on the extent to which the behavioral context
      involves active learning and whether the conflict is cross-functional. We discuss
      theoretical implications for conflict, emotions, and job satisfaction in
      organizations.

PMID- 24295534
TI  - More than g: selection quality and adverse impact implications of considering
      second-stratum cognitive abilities.
AB  - When using cognitive tests, personnel selection practitioners typically face a
      trade-off between the expected job performance and diversity of new hires. We
      review the increasingly mainstream evidence that cognitive ability is a
      multidimensional and hierarchically ordered set of concepts, and examine the
      implications for both composite test validity and subgroup differences.
      Ultimately, we recommend a strategy for differentially weighting cognitive
      subtests (i.e., second-stratum abilities) in a way that minimizes overall
      subgroup differences without compromising composite test validity. Using data
      from 2 large validation studies that included a total of 15 job families, we
      demonstrate that this strategy could lead to substantial improvement in diversity
      hiring (e.g., doubling the number of job offers extended to minority applicants)
      and to at least 8% improvement in job offers made to minority applicants, without
      decrements in expected selection quality compared to a unit-weighted cognitive
      test composite. Finally, we conduct a sensitivity analysis to examine whether the
      technique continues to perform well when applied to applicant pools of smaller
      size. We discuss prerequisites for the application of this strategy, potential
      limitations, and extensions.

PMID- 24295536
TI  - Thermoresponsive nanospheres with a regulated diameter and well-defined corona
      layer.
AB  - In the present work, we prepared core-corona-type nanospheres bearing a
      thermoresponsive polymer with a controlled chain length on their surface. The
      corona layers were composed of poly(N-isopropylacrylamide) (PNIPAAm) chains (Mn =
      3000-18,000) with a narrow polydispersity index prepared by atom-transfer radical
      polymerization (ATRP). Nanospheres were prepared by dispersion copolymerization
      of styrene with the PNIPAAm macromonomer in a polar solvent. The obtained
      nanospheres were monodisperse in diameter. The diameter of the nanospheres was
      regulated either by the number or chain length of the PNIPAAm macromonomers. In
      fact, the nanosphere diameter was regulated from ca. 100 to 1000 nm. When two
      types of PNIPAAm macromonomers are used, the obtained nanospheres have two
      different kinds of PNIPAAm on their surface. The surface of the nanospheres was
      observed to be thermoresponsive nanosphere in 0, 50, 100 mmol L(-1) NaCl aqueous
      solution. The nanosphere diameter and the surface-grafted polymer were
      concurrently adjusted for use in biomedical applications.

PMID- 24295535
TI  - Oxytocin receptor gene variation predicts empathic concern and autonomic arousal
      while perceiving harm to others.
AB  - Recent research indicates that the neuropeptide oxytocin and the gene for the
      oxytocin receptor (OXTR) have been implicated in the modulation of various social
      behaviors, including those related to empathy and sensitivity to others. In this
      study, we examine the hypothesis that genetic variation in OXTR is associated
      with autonomic reactions when perceiving others in distress. We also explore the
      possibility that individual disposition in empathic concern would differ by OXTR
      genotype. To address these questions, 51 male participants (18-35 years of age),
      genotyped for OXTR rs53576, viewed a social interaction containing high levels of
      individual distress and apparent physical pain. Electrodermal activity, a measure
      of sympathetic nervous system activity, was collected during the presentation of
      the stimuli. Participants also completed a self-report dispositional measure of
      empathy prior to starting the study and provided ratings of arousal while viewing
      the stimuli. OXTR variant rs53576 GG individuals showed increased levels of
      sympathetic and subjective arousal in response to the stimuli compared to A
      allele carriers. GG homozygotes also expressed greater levels of empathic
      concern. These findings support the importance of the oxytocin receptor variation
      in emotional and physiological reactions to the affective experiences of other
      conspecifics.

PMID- 24295537
TI  - Psychopathy, intelligence, and impulsivity in German violent offenders.
AB  - Previous studies have reported numerous correlations between psychopathy and
      various personality traits, behavioural tendencies or clinical characteristics.
      The present study examined in greater depth the relationships between the
      components of psychopathy as measured by the Psychopathy Checklist-Revised (PCL
      R) and intelligence as well as impulsivity. A total of ninety male violent
      offenders were recruited from a prison and a forensic-psychiatric hospital in
      Germany. All of the subjects were assessed using the PCL-R, the Barratt
      Impulsiveness Scale (BIS-11), and a short version of the German Wechsler Adult
      Intelligence Scale (WIP). As expected, a canonical correlation analysis showed a
      negative association between spatial intelligence and the Factor 2 subtotal on
      the PCL-R (reckless lifestyle/antisociality). In addition, our results agreed
      with the assumption of an association between impulsivity and the subtotal for
      PCL-R Factor 2. The positive relationship between verbal intelligence and the
      subtotal for Factor 1 of the PCL-R (insincere, manipulative conduct/affective
      deficits) vanished after controlling for educational level. The results indicate
      that there is a relationship between the spatial components of intelligence and
      the concept of psychopathy as described by Hare. This result supports the spatial
      impairment aetiological model of antisocial behaviour. 

PMID- 24295538
TI  - First report from the Swedish National Forensic Psychiatric Register (SNFPR).
AB  - To the best of our knowledge, the present register is the only nationwide
      forensic psychiatric patient register in the world. The aim of this article is to
      describe the content of the Swedish National Forensic Psychiatric Register
      (SNFPR) for Swedish forensic patients for the year 2010. The subjects are
      individuals who, in connection with prosecution due to criminal acts, have been
      sentenced to compulsory forensic psychiatric treatment in Sweden. The results
      show that in 2010, 1476 Swedish forensic patients were assessed in the SNFPR;
      1251 (85%) were males and 225 (15%) were females. Almost 60% of the patients had
      a diagnosis of schizophrenia, with a significantly higher frequency among males
      than females. As many as 70% of the patients had a previous history of outpatient
      psychiatric treatment before becoming a forensic psychiatric patient, with a mean
      age at first contact with psychiatric care of about 20 years old for both sexes.
      More than 63% of the patients had a history of addiction, with a higher
      proportion of males than females. Furthermore, as many as 38% of all patients
      committed crimes while under the influence of alcohol and/or illicit drugs. This
      was more often the case for men than for women. Both male and female patients
      were primarily sentenced for crimes related to life and death (e.g., murder,
      assault). However, there were more females than males in treatment for general
      dangerous crimes (e.g., arson), whereas men were more often prosecuted for crimes
      related to sex. In 2010, as many as 70% of all forensic patients in Sweden had a
      prior sentence for a criminal act, and males were prosecuted significantly more
      often than females. The most commonly prescribed pharmaceuticals for both genders
      were antipsychotics, although more women than men were prescribed other
      pharmaceuticals, such as antidepressants, antiepileptics, and anxiolytics. The
      result from the present study might give clinicians an opportunity to reflect
      upon and challenge their traditional treatment methods.

PMID- 24295539
TI  - Napsin A is possibly useful marker to predict the tumorigenic potential of lung
      bronchiolo-alveolar hyperplasia in F344 rats.
AB  - There are 2 types of bronchiolo-alveolar hyperplasia found in rat lungs. One is
      'inflammatory hyperplasia' with a potential to recover in future with removal of
      the stimulating insult and the other is 'latent tumorigenic hyperplasia' as an
      independent preneoplastic lesion for adenocarcinoma. In the present experiment,
      we focused on rat lung bronchiolo-alveolar hyperplasia induced by 4-(methyl
      nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which decreases with time after
      induction and reverts to normal, or by N-bis(2-hydroxypropyl)nitrosamine (DHPN),
      with tumorigenic potential to progress to adenoma and adenocarcinoma. Though NNK
      is a typical carcinogen inducing lung adenocarcinoma in female A/J mice, the
      tumorigenic potential by NNK in rats is weak. Differences between hyperplasias
      induced by DHPN and by NNK were here examined immunohistochemically. Formalin
      fixed paraffin embedded lung samples with hyperplastic and inflammatory lesions
      were obtained from rats exposed to DHPN or NNK and from lung inflammation models
      induced with fine particles like CuO, NiO and quartz. The 19 markers were
      examined immunohistochemically. Napsin A, in the inflammatory lesions and
      hyperplasia induced by NNK, was positive for macrophages and secretions in the
      alveoli spaces but less so in the walls of the alveoli. In the proliferative
      lesions including hyperplasia induced by DHPN, strong positive staining for
      napsin A was observed in the walls of the alveoli. Thus high expression was
      suggested to be possibly useful for detecting tumorigenic potential of rat lung
      hyperplasia. 

PMID- 24295540
TI  - A clinical study of attention-deficit/hyperactivity disorder in preschool
      children--prevalence and differential diagnoses.
AB  - OBJECTIVE: We aimed to examine (1) the prevalence and characteristics of ADHD in
      preschool children, and (2) differential diagnoses among children who display
      symptoms of inattention and hyperactivity-impulsivity in early childhood.
      METHODS: The participants were children living in Kanie-cho, in Japan's Aichi
      Prefecture, who underwent their age 5 exams at the municipal health center
      between April 2009 and March 2011. We first extracted children who were observed
      to be inattentive or hyperactive-impulsive during their age 5 exams and
      considered as possibly having ADHD. We conducted follow-ups with these children
      using post-examination consultations, visits to preschools, and group
      rehabilitation. The results of the age 5 exams were combined with behavior
      observations and interview content obtained during subsequent follow-ups. A child
      psychiatrist and several clinical psychologists discussed these cases and made a
      diagnosis in accordance with the DSM-IV-TR. RESULTS: 91 (15.6%) of the 583
      children selected were considered as possibly having ADHD; we were able to
      conduct follow-ups with 83 of the 91 children. Follow-up results showed that 34
      children (5.8% of all participants) remained eligible for a diagnosis of ADHD.
      Diagnoses for the remaining children included: pervasive developmental disorders
      (six children, or 6.6% of suspected ADHD children), intellectual comprehension
      problems (four children, or 4.4%), anxiety disorders (seven children, or 7.7%),
      problems related to abuse or neglect (four children, or 4.4%), a suspended
      diagnosis for one child (1.1%), and unclear diagnoses for 29 children (31.9%).
      CONCLUSIONS: ADHD tendencies in preschool children vary with changing situations
      and development, and the present study provides prevalence estimates that should
      prove useful in establishing a diagnostic baseline.

PMID- 24295541
TI  - Methodologies to assess muscle co-contraction during gait in people with
      neurological impairment - a systematic literature review.
AB  - PURPOSE: To review the methodologies used to assess muscle co-contraction (MCo)
      with surface electromyography (sEMG) during gait in people with neurological
      impairment. METHODS: The Scopus (1995-2013), Web of Science (1970-2013), PubMed
      (1948-2013) and B-on (1999-2013) databases were searched. Articles were included
      when sEMG was used to assess MCo during gait in people with impairment due to
      central nervous system disorders (CNS). RESULTS: Nineteen articles met the
      inclusion criteria and most studied people with cerebral palsy and stroke. No
      consensus was identified for gait assessment protocols (surfaces, speed,
      distance), sEMG acquisition (electrodes position), analysis of sEMG data
      (filters, normalisation techniques) and quantification of MCo (agonist-antagonist
      linear envelopes overlapping or agonist-antagonist overlapping periods of muscles
      activity, onset delimited). CONCLUSION: Given the wide range of methodologies
      employed, it is not possible to recommend the most appropriate for assessing MCo.
      Researchers should adopt recognized standards in future work. This is needed
      before consensus about the role that MCo plays in gait impairment in neurological
      diseases and its potential as a target for gait rehabilitation can be determined.

PMID- 24295542
TI  - Frequency analysis of lower extremity electromyography signals for the
      quantitative diagnosis of dystonia.
AB  - The purpose of this study was to develop an objective, quantitative tool for the
      diagnosis of lower extremity dystonia. Frequency domain analysis was performed on
      surface and fine-wire electromyography (EMG) signals collected from the lower
      extremity musculature of ten patients with suspected dystonia while performing
      walking trials at self-selected speeds. The median power frequency (MdPF) and
      percentage of total power contained in the low frequency range (%AUCTotal) were
      determined for each muscle studied. Muscles exhibiting clinical signs of dystonia
      were found to have a shift of the MdPF to lower frequencies and a simultaneous
      increase in the %AUCTotal. A threshold frequency of 70Hz identified dystonic
      muscles with 73% sensitivity and 63% specificity. These results indicate that
      frequency analysis can accurately distinguish dystonic from non-dystonic muscles.

PMID- 24295543
TI  - Corrective sitting strategies: An examination of muscle activity and spine
      loading.
AB  - The purpose of this study was to quantify the load on the lumbar spine of
      subjects when they are asked to adjust from a slouched sitting posture into an
      upright posture with one of three different strategies: "free" (no instruction)
      and two coached patterns: "lumbopelvic" dominant and "thoracic" dominant. The
      activity of selected muscles and kinematic data was recorded from 20 volunteers
      while performing the three movement patterns to adjust sitting posture. Moments
      and forces at the lumbar spine were computed from an anatomically detailed model
      that uses kinematics and muscle activation as input variables. The lumbopelvic
      pattern produces less joint moment on the lumbar spine (on average 31.2+/-3.9Nm)
      when compared to the thoracic pattern (43.8+/-5.8Nm). However, the joint
      compression force was similar for these two patterns, but it was smaller in the
      free pattern, when no coaching was given (lumbopelvic: 1279+/-112N, thoracic:
      1367+/-(125N, free: 1181+/-118N). Lower thoracic erector muscle activity and
      higher lumbar erector activity were measured in the lumbopelvic pattern in
      comparison with the other two. In summary the lumbopelvic pattern strategy using
      predominantly the movement of anterior pelvic tilt results in smaller joint
      moments on the lumbar spine and also positions the lumbar spine closest to the
      neutral posture minimizing passive tissue stress. This may be the strategy of
      choice for people with low back flexion intolerance. 

PMID- 24295544
TI  - Decreased fibularis reflex response during inversion perturbations in FAI
      subjects.
AB  - Investigate reflex responses in muscles throughout the lower limb and low back
      during sudden inversion perturbations in individuals with and without Functional
      Ankle Instability (FAI) while walking. Forty subjects participated in the study.
      Surface electromyogram recordings were obtained from the fibularis (FIB), gluteus
      medius (GM), erector spinae (ES), and sternocleidomastoid (SCM) of the
      injured/matched side as well as the uninjured/matched contralateral side
      (FIB_CLS, GM_CLS, or ES_CLS). Latency and amplitude data were collected while
      subjects were walking on a custom-built perturbation walkway. The onset of the
      short-latency stretch reflex of the FIB was significantly later in the injured
      side of the FAI individuals when compared to the control group (P=0.009). Both
      the short and long latency reflex amplitude was significantly smaller in the FIB
      muscle in the FAI group than in the control group (P<0.008). No significant
      differences in latency or amplitude reflex responses were identified between the
      two groups in the GM, ES, FIB_CLS, GM_CLS, or ES_CLS (P>.05). Interpretation of
      these results indicate that during a dynamic perturbation task individuals with
      FAI demonstrate longer fibularis muscle latencies on the injured side while no
      significant changes in the proximal muscle groups. Additionally, short and long
      latency reflex amplitude was significantly decreased in FAI individuals. 

PMID- 24295545
TI  - Altered spinal kinematics and muscle recruitment pattern of the cervical and
      thoracic spine in people with chronic neck pain during functional task.
AB  - Knowledge on the spinal kinematics and muscle activation of the cervical and
      thoracic spine during functional task would add to our understanding of the
      performance and interplay of these spinal regions during dynamic condition. The
      purpose of this study was to examine the influence of chronic neck pain on the
      three-dimensional kinematics and muscle recruitment pattern of the cervical and
      thoracic spine during an overhead reaching task involving a light weight transfer
      by the upper limb. Synchronized measurements of the three-dimensional spinal
      kinematics and electromyographic activities of cervical and thoracic spine were
      acquired in thirty individuals with chronic neck pain and thirty age- and gender
      matched asymptomatic controls. Neck pain group showed a significantly decreased
      cervical velocity and acceleration while performing the task. They also displayed
      with a predominantly prolonged coactivation of cervical and thoracic muscles
      throughout the task cycle. The current findings highlighted the importance to
      examine differential kinematic variables of the spine which are associated with
      changes in the muscle recruitment in people with chronic neck pain. The results
      also provide an insight to the appropriate clinical intervention to promote the
      recovery of the functional disability commonly reported in patients with neck
      pain disorders. 

PMID- 24295546
TI  - Test-retest reliability and responsiveness of gaze stability and dynamic visual
      acuity in high school and college football players.
AB  - OBJECTIVES: The purpose of this study was to establish reliability and
      responsiveness of the dynamic visual acuity test (DVAT) at head speeds of 150-200
      degrees per second (deg/s) and the gaze stabilization test (GST) in high school
      and college football players. DESIGN: Reliability design. PARTICIPANTS: Fifty
      high school and college football athletes completed the DVAT and GST in both the
      yaw (horizontal) and pitch (vertical) planes twice within two weeks. RESULTS:
      Test-retest reliability for the DVAT was good in yaw, Intraclass Correlation
      Coefficient (ICC) = 0.770, and moderate/good in pitch, ICC = 0.725. Minimal
      detectable change (MDC) was 0.16 logMAR for yaw and 0.21 logMAR for pitch. GST
      reliability was moderate in yaw, ICC = 0.634, and poor in pitch, ICC = 0.411.
      MDCs were 73.4 deg/s (yaw) and 81.2 deg/s (pitch). CONCLUSIONS: The DVAT is
      reliable at high head speeds in high school and college football athletes in both
      yaw and pitch. GST head speeds were higher than previously reported in the
      literature, but reliability of this tool for this population was poor to
      moderate. From a clinical perspective, DVAT may be reliably used in the
      assessment of high school and college football athletes; however, GST requires
      further evaluation.

PMID- 24295547
TI  - Usefulness of the troponin-ejection fraction product to differentiate stress
      cardiomyopathy from ST-segment elevation myocardial infarction.
AB  - The presentation of stress cardiomyopathy (SC) with nonobstructive coronary
      artery disease mimics that of ST-segment elevation myocardial infarction (STEMI)
      due to coronary occlusion. No single parameter has been successful in
      differentiating the 2 entities. We thus sought to develop a noninvasive clinical
      tool to discriminate between these 2 conditions. We retrospectively reviewed 59
      consecutive cases of SC at our institution from July 2005 through June 2011 and
      compared those with 60 consecutives cases of angiographically confirmed STEMI
      treated with primary percutaneous coronary intervention in the same period. All
      patients underwent acute echocardiography, and the peak troponin I level was
      determined. The troponin-ejection fraction product (TEFP) was derived by
      multiplying the peak troponin I level and the echocardiographically derived left
      ventricular ejection fraction. Comparing the SC and STEMI groups, the mean left
      ventricular ejection fraction at the time of presentation was 30 +/- 9% versus 44
      +/- 11%, respectively (p <0.001), and the peak troponin I was 7.6 +/- 18 versus
      102.2 +/- 110.3 ng/dl, respectively (p <0.001). The mean TEFP was thus 182 +/-
      380 and 4,088 +/- 4,244 for the SC and STEMI groups, respectively (p <0.001).
      Receiver operating characteristic curve analysis showed that a TEFP value >=250
      had a sensitivity of 95%, a specificity of 87%, a negative predictive value of
      94%, a positive predictive value of 88%, and an overall accuracy of 91% to
      differentiate a true STEMI from SC (C-statistic 0.91 +/- 0.02, p <0.001). In
      conclusion, for patients not undergoing emergent angiography, the TEFP may be
      used with high accuracy to differentiate SC with nonobstructive coronary artery
      disease from true STEMI due to coronary occlusion.

PMID- 24295548
TI  - Impact of patients' arrival time on the care and in-hospital mortality in
      patients with non-ST-elevation myocardial infarction.
AB  - Only a few studies have focused on the clinical characteristics and outcomes of
      non-ST-segment myocardial infarction (NSTEMI) during off-hours. The purpose of
      this study was to compare the impact of patients' arrival time on the care of
      NSTEMI and whether this pattern might affect hospital mortality. This study
      analyzed 4,736 NSTEMI patients included in the Korea Acute Myocardial Infarction
      Registry from November 2005 to January 2008. Patients' arrival time was
      classified into regular hours (weekdays, 9:00 a.m. to 6:00 p.m.) and off-hours
      (weekdays 18:01 p.m. to 8:59 a.m., weekends, and holidays). A subtotal of 2,225
      (46.9%) patients was admitted during off hours, compared with 2,511 (53.1%)
      patients with regular-hour admission. A higher proportion of patients admitted
      during off-hours had a higher Killip class, had more frequent cardiopulmonary
      resuscitation, were less likely to receive percutaneous coronary intervention
      (PCI) (67.7% vs 72.7%, p <0.001), and had longer door-to-balloon times (28 hours,
      interquartile range: 11 to 63 vs 23 hours, interquartile range 4 to 67, p
      <0.001). Although unadjusted hospital mortality was associated with admission
      during off-hours (4.5% vs 3.3%, p = 0.023), after adjusting for all patients
      covariates, the difference in mortality was attenuated and was no longer
      statistically significant (odds ratio 0.94, 95% confidence interval 0.59 to 1.48,
      p = 0.793). In conclusion, despite receiving fewer PCIs and having substantially
      longer waiting times to PCI, patients admitted during off-hours may not be at
      risk for increased in-hospital mortality. If patients are treated within an
      appropriate reperfusion strategy according to their clinical risk, arrival time
      may not influence on mortality.

PMID- 24295549
TI  - Usefulness of a combination of monocyte chemoattractant protein-1, galectin-3,
      and N-terminal probrain natriuretic peptide to predict cardiovascular events in
      patients with coronary artery disease.
AB  - Patients with coronary artery disease may develop not only ischemic events but
      also heart failure and death due to previous myocardial damage. The purpose of
      this study was to test the prognostic value of a panel of plasma biomarkers
      related to vascular (monocyte chemoattractant protein-1 [MCP-1] and soluble tumor
      necrosis factor-like weak inducer of apoptosis) and myocardial damage (galectin
      3, N-terminal fragment of brain natriuretic peptide [NT-proBNP], and neutrophil
      gelatinase-associated lipocalin) in 706 patients with chronic coronary artery
      disease followed for 2.2 +/- 0.99 years. Secondary outcomes were the incidence of
      acute ischemic events (ST elevation myocardial infarction, non-ST elevation acute
      coronary syndrome, stroke, or transient ischemic attack) and death or heart
      failure. The primary outcome was the combination of the secondary outcomes. Cox
      proportional hazards model was used for analysis. Fifty-three patients developed
      acute ischemic events. Increasing MCP-1 plasma levels (p = 0.002), age, and body
      mass index predicted this outcome independently. Thirty-three patients developed
      death and/or heart failure. Galectin-3 (p = 0.007), NT-proBNP plasma levels (p =
      0.004), hypertension, glomerular filtration rate, and the use of nitrates and
      anticoagulants were associated with this outcome independently. The development
      of the primary outcome was predicted independently by MCP-1 (p <0.001), NT-proBNP
      (p = 0.005), and galectin-3 (p = 0.019); hypertension; atrial fibrillation; and
      treatment with nitrates. Every biomarker with a value above the median increased
      the risk of developing this outcome by 1.832 (95% confidence interval 1.356 to
      2.474, p <0.001). High-sensitivity C-reactive protein and lipid levels were not
      associated with any outcome. In conclusion, increasing MCP-1, galectin-3, and NT
      proBNP plasma levels are associated with a greater incidence of cardiovascular
      events.

PMID- 24295550
TI  - Racial and ethnic differences in statin prescription and clinical outcomes among
      hospitalized patients with coronary heart disease.
AB  - We aimed to evaluate the association among race and ethnicity, statin
      prescription, and clinical outcomes among hospitalized patients with coronary
      heart disease (CHD), adjusted for confounders. Racial and ethnic disparities in
      CHD outcomes may be related to differential uptake of preventive medications, but
      data from real-world settings are limited. This was a 1-year prospective study of
      patients with preexisting CHD without a documented contraindication to statin (n
      = 3,067, 35% black or Hispanic, 65% white or Asian, 35% women) who participated
      in an National Heart, Lung and Blood Institute clinical outcome study of patients
      admitted to a cardiovascular service. Baseline clinical and medication data and
      30-day and 1-year outcomes (death or rehospitalization) were documented by
      electronic medical record, National Death Index, and/or standardized mail survey.
      Logistic regression was used to evaluate associations among race and ethnicity,
      statin prescription, and outcomes adjusted for demographics and co-morbidities.
      Black and Hispanic patients were more likely to be dead or rehospitalized at 1
      year (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.06 to 1.43) and less
      likely to report statin use before admission (62% vs 72%, adjusted OR 0.64, 95%
      CI 0.54 to 0.76) than whites and Asians; statin prescription was similar at
      discharge among blacks and Hispanics (81%) versus whites and Asians (84%). Black
      and Hispanic patients were more likely to have hypertension, diabetes, or renal
      failure and less likely to have health insurance than whites and Asians (p
      <0.05). The increased 1-year odds of death or rehospitalization in minorities
      versus whites and Asians were explained by demographics and co-morbidities not by
      differential statin prescription (adjusted OR 1.10, 95% CI 0.93 to 1.30). In
      conclusion, in this study of hospitalized patients with preexisting CHD,
      differential statin prescription did not explain racial and ethnic disparities in
      1-year outcomes. Efforts to reduce CHD rehospitalizations should consider the
      greater burden of co-morbidities among racial and ethnic minorities.

PMID- 24295551
TI  - Viral infections and systemic sclerosis.

PMID- 24295554
TI  - Composition and growth behavior of the surface and electrolyte decomposition
      layer of/on a commercial lithium ion battery LixNi1/3Mn1/3Co1/3O2 cathode
      determined by sputter depth profile X-ray photoelectron spectroscopy.
AB  - A detailed X-ray photoelectron spectroscopy (XPS) study of the surface and
      electrolyte decomposition layer of a LixNi1/3Mn1/3Co1/3O2 (NMC) cathode from
      commercial NMC/graphite cells by intense sputter depth profiling (SDP) using a
      polyatomic ion gun is provided. Cathodes of a cell after electrochemical
      formation and a cell at a state of initial capacity (SOIC) of 80%, which was
      reached after 2500 full cycles at 30  degrees C, are investigated. 

PMID- 24295555
TI  - Maternal personality and psychopathology as determinants of parenting behavior: a
      quantitative integration of two parenting literatures.
AB  - A substantial literature has examined the association between parenting behavior
      and maternal psychological characteristics (i.e., personality and
      psychopathology). Although research has provided evidence indicating that
      personality and psychopathology are not independent of one another, parenting
      research has mainly focused on these characteristics separately. In the present
      study, I quantitatively integrated these literatures through meta-analytic path
      analysis. First, meta-analyses were conducted on articles, book chapters, and
      dissertations that examined associations between personality or psychopathology
      and warmth or control in mothers of children age 12 months or older. Using mixed
      effects regression, meta-analyses revealed significant, small effect sizes
      suggesting that low levels of neuroticism and psychopathology and high levels of
      agreeableness, extraversion, and conscientiousness were associated with adaptive
      parenting. Moderator analyses indicated that variability among individual studies
      was partially explained by report method, study design, and conceptualizations of
      parenting behavior. Meta-analytic path analyses showed that the observed
      associations between maternal personality/psychopathology and parenting behaviors
      as reported in the literature may be explained by variance shared among these
      psychological characteristics. Furthermore, some maternal psychological
      characteristics explained a significantly larger portion of variance in parenting
      behavior than others. Findings supported the proposal that maternal personality
      and psychopathology are not independent in the associations they demonstrate with
      parenting behaviors and that these areas of research can be integrated. The
      present study is limited by including only mothers, excluding infants, and using
      cross-sectional analyses. However, results have implications for future
      conceptualizations of maternal psychological characteristics as determinants of
      parenting behaviors and for the refinement of parenting interventions.

PMID- 24295552
TI  - Reprint of: Mapping connectivity in the developing brain.
AB  - Recently, there has been a wealth of research into structural and functional
      brain connectivity, and how they change over development. While we are far from a
      complete understanding, these studies have yielded important insights into human
      brain development. There is an ever growing variety of methods for assessing
      connectivity, each with its own advantages. Here we review research on the
      development of structural and/or functional brain connectivity in both typically
      developing subjects and subjects with neurodevelopmental disorders. Space
      limitations preclude an exhaustive review of brain connectivity across all
      developmental disorders, so we review a representative selection of recent
      findings on brain connectivity in autism, Fragile X, 22q11.2 deletion syndrome,
      Williams syndrome, Turner syndrome, and ADHD. Major strides have been made in
      understanding the developmental trajectory of the human connectome, offering
      insight into characteristic features of brain development and biological
      processes involved in developmental brain disorders. We also discuss some common
      themes, including hemispheric specialization - or asymmetry - and sex
      differences. We conclude by discussing some promising future directions in
      connectomics, including the merger of imaging and genetics, and a deeper
      investigation of the relationships between structural and functional
      connectivity. 

PMID- 24295553
TI  - Reprint of "Quantitative evaluation of brain development using anatomical MRI and
      diffusion tensor imaging".
AB  - The development of the brain is structure-specific, and the growth rate of each
      structure differs depending on the age of the subject. Magnetic resonance imaging
      (MRI) is often used to evaluate brain development because of the high spatial
      resolution and contrast that enable the observation of structure-specific
      developmental status. Currently, most clinical MRIs are evaluated qualitatively
      to assist in the clinical decision-making and diagnosis. The clinical MRI report
      usually does not provide quantitative values that can be used to monitor
      developmental status. Recently, the importance of image quantification to detect
      and evaluate mild-to-moderate anatomical abnormalities has been emphasized
      because these alterations are possibly related to several psychiatric disorders
      and learning disabilities. In the research arena, structural MRI and diffusion
      tensor imaging (DTI) have been widely applied to quantify brain development of
      the pediatric population. To interpret the values from these MR modalities, a
      "growth percentile chart," which describes the mean and standard deviation of the
      normal developmental curve for each anatomical structure, is required. Although
      efforts have been made to create such a growth percentile chart based on MRI and
      DTI, one of the greatest challenges is to standardize the anatomical boundaries
      of the measured anatomical structures. To avoid inter- and intra-reader
      variability about the anatomical boundary definition, and hence, to increase the
      precision of quantitative measurements, an automated structure parcellation
      method, customized for the neonatal and pediatric population, has been developed.
      This method enables quantification of multiple MR modalities using a common
      analytic framework. In this paper, the attempt to create an MRI- and a DTI-based
      growth percentile chart, followed by an application to investigate developmental
      abnormalities related to cerebral palsy, Williams syndrome, and Rett syndrome,
      have been introduced. Future directions include multimodal image analysis and
      personalization for clinical application. 

PMID- 24295556
TI  - Efficacy and safety of fluticasone furoate 100 MUg once-daily in patients with
      persistent asthma: a 24-week placebo and active-controlled randomised trial.
AB  - Inhaled corticosteroids (ICSs) improve asthma disease control; once-daily ICS
      administration may have advantages for patients. Our objective was to assess the
      efficacy and safety of the novel ICS fluticasone furoate (FF) over 24 weeks
      versus placebo. This was a 24-week double-blind, double-dummy, placebo- and
      active-controlled study (NCT01159912) of 343 asthma patients (>=12 years) not
      controlled by their current ICS. Patients were randomised (1:1:1) to FF100 MUg,
      placebo (both administered once-daily [OD] via ELLIPTATM dry powder inhaler in
      the evening) or fluticasone propionate (FP) 250 MUg (administered twice-daily
      (BD) via DISKUSTM/ACCUHALERTM). Primary endpoint was change from baseline in pre
      dose evening forced expiratory volume in 1s (FEV1) at Week 24; change from
      baseline in % rescue-free 24-h periods was a powered secondary endpoint. Adverse
      events (AEs) were assessed. FF100 MUg OD and FP250 MUg BD significantly improved
      pre-dose evening FEV1 compared with placebo at Week 24 (+146 ml [p = 0.009] and
      +145 ml [p = 0.011], respectively). Percentage of rescue-free 24-h periods was
      increased with FF100 MUg OD (+14.8%) and FP250 MUg BD (+17.9%) compared to
      placebo (both p < 0.001). On-treatment AEs were reported by 53% (FF100 MUg OD),
      42% (FP250 MUg BD) and 40% (placebo) of patients. On-treatment severe asthma
      exacerbations were lower with FF100 MUg OD (3%) and FP250 MUg BD (2%) than
      placebo (7%). There was significant suppression of urinary cortisol at week 24
      with FF100 MUg OD (p = 0.030) and FP250 MUg BD (p = 0.036) relative to placebo.
      FF100 MUg OD, administered in the evening, achieves significant improvements in
      lung function and rescue inhaler use over 24 weeks, comparable to FP250 MUg BD
      with similar safety profile. 

PMID- 24295557
TI  - Face-sensitive brain responses measured from a four-year-old child with a custom
      sized child MEG system.
AB  - BACKGROUND: Previous magnetoencephalography (MEG) studies have failed to find a
      facesensitive, brain response-M170 in children. If this is the case, this
      suggests that the developmental trajectory of the M170 is different from that of
      its electrical equivalent, the N170. We investigated the alternative possibility
      that the child M170 may not be detectable in conventional adult-sized MEG
      systems. NEW METHOD: Brain responses to pictures of faces and well controlled
      stimuli were measured from the same four-year-old child with a custom child MEG
      system and an adult-sized MEG system. RESULTS: The goodness of fit of the child's
      head was about the same over the occipital head surface in both systems, but was
      much worse over all other parts of the head surface in the adult MEG system
      compared to the child MEG system. The face-sensitive M170 was measured from the
      child in both MEG systems, but was larger in amplitude, clearer in morphology,
      and had a more accurate source localization when measured in the child MEG
      system. COMPARISON WITH EXISTING METHOD: The custom-sized child MEG system is
      superior for measuring the face-sensitive M170 brain response in children than
      the conventional adult MEG system. CONCLUSIONS: The present results show that the
      face-sensitive M170 brain response can be elicited in a four-year-old child. This
      provides new evidence for early maturation of face processing brain mechanisms in
      humans, and offers new opportunities for the study of neurodevelopmental
      disorders that show atypical face processing capabilities, such as autism
      spectrum disorder.

PMID- 24295558
TI  - Diphtheria in Andhra Pradesh-a clinical-epidemiological study.
AB  - OBJECTIVES: Clinical diphtheria is on the increase worldwide, mainly affecting
      developing countries. We sought to understand its presentation among patients at
      Sir Ronald Ross Institute of Tropical and Communicable Diseases in Hyderabad,
      Andhra Pradesh, India. METHODS: Diphtheria patients presented with fever,
      pharyngitis, and a patch in the throat. Data collected for each patient included
      age, clinical presentation, morbidity, mortality, bacteria isolated from culture,
      and immunization status. RESULTS: Of 61 950 admissions from January 2008 to
      December 2012, 2925 (4.7%) had clinical diphtheria; 1194 had been immunized and
      1731 were non-immunized. Immunized patients had a milder disease. Culture
      positive immunized patients were positive for Corynebacterium other than
      diphtheriae (COD; n=104) or Corynebacterium diphtheriae (CD; n=23); these
      patients suffered mild disease and recovered completely. In contrast, culture
      positive non-immunized patients were positive for COD (n=11) or CD (n=412).
      Eighty-one patients (3%) died, 77 of whom were non-immunized; death was usually
      as a result of myocarditis. Seventy-three percent of deaths were in patients aged
      <5 years. CONCLUSIONS: The clinical presentation of diphtheria and its severity
      and morbidity differ considerably in immunized and non-immunized patients.
      Disease caused by CD can be deadly, while disease due to COD is mild and responds
      to treatment.

PMID- 24295559
TI  - Diagnostic contribution of (18)F-FDG-PET/CT in fever of unknown origin.
AB  - OBJECTIVES: Fever of unknown origin (FUO) remains one of the most compelling
      diagnostic issues in medicine. We aimed to evaluate the potential clinical
      contribution of 18-fluoro-2-deoxyglucose positron emission tomography/computed
      tomography ((18)F-FDG-PET/CT) in the identification of the underlying cause of
      FUO. METHODS: Fifty consecutive patients (27 men and 23 women; age range 16-88
      years) with FUO based on the revised definition criteria were included in the
      study. A diagnostic protocol including biochemistry, histopathology, and
      microbiological tests was performed and the patients were followed up. FDG-PET
      was performed in 25 of the 50 patients (12 males and 13 females; age range 16-88
      years) in order to determine the etiology of the patient's fever. PET-CT images
      were obtained with the Gemini Philips TF (18)F-FDG-PET/CT camera after a 60-min
      'standard uptake' period following an injection of a mean 330 MBq (range 290-370
      MBq) intravenous (18)F-FDG. RESULTS: A total of 21 patients were available for
      analysis of the diagnostic contribution of PET/CT (two patients were undiagnosed
      and two had non-contributory PET/CT findings). (18)F-FDG-PET/CT was able to
      precisely detect the cause of fever in 60% of the cases (n=15). The accuracy,
      sensitivity, and specificity of this imaging modality were 90.5%, 93.8%, and 80%,
      respectively. Among the cases with a true-positive (18)F-FDG-PET/CT finding
      (i.e., 15 cases), the identified underlying causes of FUO included localized
      infection (n=7), non-infective inflammatory process (n=5), and malignancy (n=3).
      CONCLUSIONS: Further studies to confirm the high diagnostic yield of (18)F-FDG
      PET/CT observed in the present study would lend support to the inclusion of this
      imaging modality in the initial diagnostic work-up of patients with suspected
      FUO.

PMID- 24295560
TI  - Pharmacogenomics of biological treatment in rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) demonstrates a high heterogeneity in
      clinical responses to treatment. Although the efficacy of biological therapy has
      undoubtedly been established, the response differs considerably between
      individuals. This variability between individuals has aroused the research for
      biomarkers predictive of treatment response. Pharmacogenomics underlying
      individual responses to drugs is rapidly developed and has the potential of
      realizing the personalized therapy in RA. This review will summarize the
      pharmacogenomics of biological therapies approved for clinical RA treatment.
      AREAS COVERED: The pharmacogenomics underlies individual responses to biological
      drugs in RA. Current studies on pharmacogenomics of biological therapy in RA are
      presented. EXPERT OPINION: The personalized treatment in RA according to
      pharmacogenomics is promising, but the available pharmacogenomic data on
      biological treatment in RA are not adequate and consistent and still require
      further larger sample studies to corroborate.

PMID- 24295561
TI  - Elevated serum levels of circulating immunoinflammation-related protein complexes
      are associated with cancer.
AB  - Disease-specific immune response-related protein complexes in the bloodstream are
      associated with disease status. We used proteomic technologies to screen novel
      circulating immunoinflammation-related protein complexes (IIRPCs) and to evaluate
      their diagnostic accuracy. The discovery study included 96 gastric cancer
      patients and 83 healthy controls and was designed to isolate and identify the
      IIRPCs. Then an independent validation study including 1366 patients with lung,
      colorectal, pancreatic, gastric, or thyroid cancer, 141 patients with other types
      of cancer, 376 patients with benign lung, colorectal, pancreatic, gastric, or
      thyroid diseases, and 3707 healthy controls was performed. We observed seven
      major patterns of the IIRPCs and confirmed the IIRPCs as personalized biomarkers
      of cancers. The levels of the IIRPCs were significantly increased in cancer
      patients compared with controls and benign patients (p < 0.0001). Each of the
      IIRPCs (a2 to a4, a6, a7, and b3 to b5) shows excellent discriminating power for
      lung, colorectal, pancreatic, and gastric cancer, with the areas under the
      receiver operating characteristic curves (AUCs) from 0.95 to 0.99 (95% CIs 0.91
      1.00), and for thyroid cancer, with the AUCs from 0.87 to 0.96 (95% CIs 0.80
      0.98). The IIRPCs can be used as a novel type of broad-spectrum and
      supramolecular biomarker for personalized cancer diagnosis. 

PMID- 24295563
TI  - Continuing asymptomatic scaphoid bone loss in scaphoid-trapezium-trapezoid joint
      pyrocarbon implants.

PMID- 24295562
TI  - Global transcriptome analysis of Clostridium thermocellum ATCC 27405 during
      growth on dilute acid pretreated Populus and switchgrass.
AB  - BACKGROUND: The thermophilic anaerobe Clostridium thermocellum is a candidate
      consolidated bioprocessing (CBP) biocatalyst for cellulosic ethanol production.
      The aim of this study was to investigate C. thermocellum genes required to
      ferment biomass substrates and to conduct a robust comparison of DNA microarray
      and RNA sequencing (RNA-seq) analytical platforms. RESULTS: C. thermocellum ATCC
      27405 fermentations were conducted with a 5 g/L solid substrate loading of either
      pretreated switchgrass or Populus. Quantitative saccharification and inductively
      coupled plasma emission spectroscopy (ICP-ES) for elemental analysis revealed
      composition differences between biomass substrates, which may have influenced
      growth and transcriptomic profiles. High quality RNA was prepared for C.
      thermocellum grown on solid substrates and transcriptome profiles were obtained
      for two time points during active growth (12 hours and 37 hours postinoculation).
      A comparison of two transcriptomic analytical techniques, microarray and RNA-seq,
      was performed and the data analyzed for statistical significance. Large
      expression differences for cellulosomal genes were not observed. We updated gene
      predictions for the strain and a small novel gene, Cthe_3383, with a putative
      AgrD peptide quorum sensing function was among the most highly expressed genes.
      RNA-seq data also supported different small regulatory RNA predictions over
      others. The DNA microarray gave a greater number (2,351) of significant genes
      relative to RNA-seq (280 genes when normalized by the kernel density mean of M
      component (KDMM) method) in an analysis of variance (ANOVA) testing method with a
      5% false discovery rate (FDR). When a 2-fold difference in expression threshold
      was applied, 73 genes were significantly differentially expressed in common
      between the two techniques. Sulfate and phosphate uptake/utilization genes, along
      with genes for a putative efflux pump system were some of the most differentially
      regulated transcripts when profiles for C. thermocellum grown on either
      pretreated switchgrass or Populus were compared. CONCLUSIONS: Our results suggest
      that a high degree of agreement in differential gene expression measurements
      between transcriptomic platforms is possible, but choosing an appropriate
      normalization regime is essential.

PMID- 24295564
TI  - Do motor subtypes of delirium in child and adolescent have a different clinical
      and phenomenological profile?
AB  - OBJECTIVE: To explore the frequency of different motor subtypes of delirium in
      children and adolescents and to study the relationship of motor subtypes with
      other symptoms, etiology and outcome of delirium. METHODS: Forty-nine consecutive
      patients, aged 8-19 years, diagnosed as having delirium as per DSM-IV-TR were
      assessed on Delirium Rating Scale-Revised 98 (DRS-R-98), amended Delirium Motor
      Symptom Scale (DMSS), delirium etiology checklist and risk factors for delirium.
      Different motoric subtypes of delirium were compared with each other for symptoms
      of delirium as assessed by DRS-R-98, risk factors, etiology and outcome. RESULTS:
      More than half (53%) of patients were classified as having hyperactive delirium,
      this was followed by the mixed (26.5%) and the hypoactive (16%) subtype. When the
      different subtypes were compared with each other, the 3 motor subtypes did not
      differ from each other in terms of frequency and severity of other symptoms
      except for minor differences. Hallucinations are more common in patients with
      hyperactive and mixed subtype. There is no significant difference in the outcome
      of delirium across different subtypes. CONCLUSION: Unlike in adults, motoric
      subtypes of delirium in child and adolescents do not differ from each other with
      respect to other symptoms, risk factors and outcome.

PMID- 24295565
TI  - Delirium in patients admitted to a cardiac intensive care unit with cardiac
      emergencies in a developing country: incidence, prevalence, risk factor and
      outcome.
AB  - AIM: To assess the incidence, prevalence, risk factors and outcome of delirium in
      patients admitted to a cardiac intensive care unit (ICU) of a tertiary care
      hospital. METHODS: Three hundred nine consecutive patients admitted to a 22-bed
      coronary care unit were screened for presence of delirium by using Confusion
      Assessment Method for Intensive Care Unit (CAM-ICU), and those found positive on
      CAM-ICU were further evaluated by a psychiatrist to confirm the diagnosis of
      delirium as per DSM-IV-TR criteria. Patients were also evaluated for the risk
      factors for delirium and outcome of delirium. RESULTS: Incidence rate of delirium
      was 9.27%, and prevalence rate was 18.77%. The risk factors identified for
      delirium in binary logistic regression analysis were hypokalemia, Sequential
      Organ Failure Assessment score, presence of cognitive deficits, receiving more
      than three medications, sepsis, hyponatremia, presence of cardiogenic shock,
      having undergone coronary artery bypass grafting, left ventricular ejection
      fraction <30, currently receiving opioids, age more than 65 years, presence of
      diabetes mellitus, presence of uncontrolled diabetes mellitus, history of
      seizures, presence of congestive cardiac failure, having undergone angioplasty,
      presence of atrial fibrillation, ongoing depression, currently receiving/taking
      benzodiazepines, warfarin, ranitidine, steroids, non-steroidal anti-inflammatory
      drugs, higher total number of medications, presence of raised creatinine,
      anaemia, hypoglycemia, Acute Physiology and Chronic Health Evaluation II score
      and Charlson Comorbidity Index score. About one fourth (n=22; 27%) of the
      patients who developed delirium died during the hospital stay in contrast to 1%
      mortality in the non-delirious group. Those with delirium also had longer stay in
      the ICU. CONCLUSIONS: Delirium is highly prevalent in the cardiac ICU setting and
      is associated with presence of many modifiable risk factors. Development of
      delirium increases the mortality risk and is associated with longer cardiac ICU
      stay.

PMID- 24295566
TI  - Quantifying the passive stretching response of human tibialis anterior muscle
      using shear wave elastography.
AB  - BACKGROUND: Quantifying passive stretching responses of individual muscles helps
      the diagnosis of muscle disorders and aids the evaluation of
      surgical/rehabilitation treatments. Utilizing an animal model, we demonstrated
      that shear elastic modulus measured by supersonic shear wave elastography
      increases linearly with passive muscle force. This study aimed to use this state
      of-the-art technology to study the relationship between shear elastic modulus and
      ankle dorsi-plantarflexion angle of resting tibialis anterior muscles and extract
      physiologically meaningful parameters from the elasticity-angle curve to better
      quantify passive stretching responses. METHODS: Elasticity measurements were made
      at resting tibialis anterior of 20 healthy subjects with the ankle positioned
      from 50 degrees  plantarflexion to up to 15 degrees  dorsiflexion at every 5
      degrees  for two cycles. Elasticity-angle data was curve-fitted by optimizing
      slack angle, slack elasticity, and rate of increase in elasticity within a
      piecewise exponential model. FINDINGS: Elasticity-angle data of all subjects were
      well fitted by the piecewise exponential model with coefficients of determination
      ranging between 0.973 and 0.995. Mean (SD) of slack angle, slack elasticity, and
      rate of increase in elasticity were 10.9 degrees  (6.3 degrees ), 5.8 (1.9) kPa,
      and 0.0347 (0.0082) respectively. Intraclass correlation coefficients of each
      parameter were 0.852, 0.942, and 0.936 respectively, indicating excellent test
      retest reliability. INTERPRETATION: This study demonstrated the feasibility of
      using supersonic shear wave elastography to quantify passive stretching
      characteristics of individual muscle and provided preliminary normative values of
      slack angle, slack elasticity, and rate of increase in elasticity for human
      tibialis anterior muscles. Future studies will investigate diagnostic values of
      these parameters in clinical applications.

PMID- 24295568
TI  - Editorial: special issue on finfish immunology.

PMID- 24295567
TI  - Type I interferon-mediated pathway interacts with peroxisome proliferator
      activated receptor-gamma (PPAR-gamma): at the cross-road of pancreatic cancer
      cell proliferation.
AB  - Pancreatic adenocarcinoma remains an unresolved therapeutic challenge because of
      its intrinsically refractoriness to both chemo- and radiotherapy due to the
      complexity of signaling and the activation of survival pathways in cancer cells.
      Recent studies have demonstrated that the combination of some drugs, targeting
      most of aberrant pathways crucial for the survival of pancreatic cancer cells may
      be a valid antitumor strategy for this cancer. Type I interferons (IFNs) may have
      a role in the pathogenesis and progression of pancreatic adenocarcinoma, but the
      limit of their clinical use is due to the activation of tumor resistance
      mechanisms, including JAK-2/STAT-3 pathway. Moreover, aberrant constitutive
      activation of STAT-3 proteins has been frequently detected in pancreatic
      adenocarcinoma. The selective targeting of these cell survival cascades could be
      a promising strategy in order to enhance the antitumor effects of type I IFNs.
      The activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma),
      on the other hand, has a suppressive activity on STAT-3. In fact, PPAR-gamma
      agonists negatively modulate STAT-3 through direct and/or indirect mechanisms in
      several normal and cancer models. This review provides an overview on the current
      knowledge about the molecular mechanisms and antitumor activity of these two
      promising classes of drugs for pancreatic cancer therapy. Finally, the
      synergistic antiproliferative activity of combined IFN-beta and troglitazone
      treatment on pancreatic cancer cell lines, evaluated in vitro, and the consequent
      potential clinical applications will be discussed. 

PMID- 24295569
TI  - Transcatheter arterial chemoembolization with doxorubicin-eluting superabsorbent
      polymer microspheres in the treatment of hepatocellular carcinoma: midterm follow
      up.
AB  - PURPOSE: To investigate prospectively the safety, tolerability, and efficacy of
      transarterial chemoembolization using superabsorbent polymer (SAP) microspheres
      loaded with doxorubicin for the treatment of hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: During the years 2006-2011, 64 patients underwent 144
      transarterial chemoembolization with SAP microspheres procedures. Most of the
      patients were staged as Barcelona Clinic Liver Cancer class B (65%). The most
      frequent underlying liver diseases were hepatitis C (35%) and alcoholic liver
      disease (28%) resulting in Child-Pugh A (73.4%) or Child-Pugh B (17%) liver
      cirrhosis. Tumor response was assessed using modified Response Evaluation
      Criteria in Solid Tumors with magnetic resonance (MR) imaging performed 4-6 weeks
      after each procedure. RESULTS: Serious adverse events (n = 9) were ischemic or
      infectious in nature. Transarterial chemoembolization with SAP microspheres
      resulted in objective response rates of 67.5%, 44.5%, and 25% after first,
      second, and third sessions. There were 16 patients (25%) who underwent orthotopic
      liver transplantation after transarterial chemoembolization with SAP
      microspheres, of whom 2 experienced recurrent disease. During a median follow-up
      time of 14 months (range, 2-55 mo), 26 patients (40.5%) died. Median overall and
      transplant-free survivals were 20.5 months (95% confidence interval, 13.2-27.7)
      and 18 months (95% confidence interval, 14.2-21.8), respectively. CONCLUSIONS:
      Transarterial chemoembolization with SAP microspheres has an excellent safety
      profile in cirrhotic patients, even in the presence of advanced liver disease
      (Child-Pugh B) or advanced stages of HCC. This treatment produced meaningful
      tumor response rates as assessed by MR imaging.

PMID- 24295571
TI  - Evaluation of 16SpathDB 2.0, an automated 16S rRNA gene sequence database, using
      689 complete bacterial genomes.
AB  - Interpretation of 16S rRNA sequences is a difficult problem faced by clinical
      microbiologists and technicians. In this study, we evaluated the updated
      16SpathDB 2.0 database, using 689 16S rRNA sequences from 689 complete genomes of
      medically important bacteria. Among these 689 16S rRNA sequences, none was
      wrongly identified, with 35.8% reported as a single bacterial species having >98%
      identity with the query sequence (category 1), 63.9% reported as more than 1
      bacterial species having >98% identity with the query sequence (category 2), 0.3%
      reported to the genus level (category 3), and none reported as no match (category
      4). For the 16S rRNA sequences of non-duplicated bacterial species reported as
      category 1 or 2, the percentage of bacterial species reported as category 1 was
      significantly higher for anaerobic Gram-positive/Gram-negative bacteria than
      aerobic/facultative anaerobic Gram-positive/Gram-negative bacteria. 16SpathDB 2.0
      is a user-friendly and accurate database for 16S rRNA sequence interpretation in
      clinical laboratories. 

PMID- 24295570
TI  - Ghrelin stimulates proliferation, migration and differentiation of neural
      progenitors from the subventricular zone in the adult mice.
AB  - Ghrelin has been shown to regulate neurogenesis in the hippocampus. The aim of
      this study was to investigate the possible influence of ghrelin on cell
      proliferation and neuroblast formation in the subventricular zone (SVZ) and
      rostral migratory system (RMS) and generation of interneurons in the olfactory
      bulb (OB). We found that ghrelin receptors were expressed in the SVZ-RMS-OB
      system. Ghrelin knockout (GKO) mice have fewer proliferating neural progenitor
      cells and neuroblasts in the SVZ, while ghrelin administration attenuated these
      changes. We also found that not only the number of BrdU-labeled cells but also
      the fraction of migratory neuroblasts in the RMS was decreased in the GKO mice
      compared with controls. Treatment of GKO mice with ghrelin restored these numbers
      to the wild-type control values. Far fewer BrdU/NeuN double-labeled cells were
      found in the OB of GKO mice than in wild-type mice 4 weeks after labeling, which
      were increased by ghrelin replacement. GKO mice showed less numbers of
      BrdU/calbindin, BrdU/calretinin and BrdU/tyrosine hydroxylase double-labeled
      cells in the periglomerular layer of the OB. However, these numbers were
      increased to wild-type values after ghrelin administration. Finally, in the GH
      deficient spontaneous dwarf rats, ghrelin increased the number of progenitor
      cells and neuroblasts in the SVZ, without significant effect on the
      differentiation in the OB. These findings suggest that ghrelin is involved in the
      regulation of proliferation of progenitor cells in the SVZ, the number of
      migratory neuroblasts in the SVZ, and the differentiation of interneurons in the
      OB.

PMID- 24295573
TI  - Effects of histone deacetylase inhibitors on alloresponses.

PMID- 24295574
TI  - Seven decades of "advances".
AB  - The field of carbohydrate science, as documented in the 70 volumes of Advances in
      Carbohydrate Chemistry (and Biochemistry) during the years 1944 through 2014, is
      surveyed. Subject areas detailed in individual volumes cover a broad range to
      include fundamental structural studies, synthesis, reactivity, mechanisms,
      analytical methodology, enzymology, biological and medicinal applications, food
      technology, and industrial and commercial aspects. The contributions of many
      prominent research leaders in the carbohydrate field are recorded in biographical
      memoirs. Stages in the development of internationally accepted systems for naming
      carbohydrate structures and for their graphical depiction are noted, and indexing
      questions for retrieval of data are addressed. 

PMID- 24295575
TI  - Preface.

PMID- 24295572
TI  - Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease
      after related-donor reduced-intensity conditioning allogeneic haemopoietic stem
      cell transplantation: a phase 1/2 trial.
AB  - BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more
      widespread application of allogeneic haemopoietic stem-cell transplantation.
      Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate
      GVHD in preclinical models. We aimed to study the safety and activity of
      vorinostat, in combination with standard immunoprophylaxis, for prevention of
      GVHD in patients undergoing related-donor reduced-intensity conditioning
      haemopoietic stem-cell transplantation. METHODS: Between March 31, 2009, and Feb
      8, 2013, we did a prospective, single-arm, phase 1/2 study at two centres in the
      USA. We recruited adults (aged >=18 years) with high-risk haematological
      malignant diseases who were candidates for reduced-intensity conditioning
      haemopoietic stem-cell transplantation and had an available 8/8 or 7/8 HLA
      matched related donor. All patients received a conditioning regimen of
      fludarabine (40 mg/m(2) daily for 4 days) and busulfan (3.2 mg/kg daily for 2
      days) and GVHD immunoprophylaxis of mycophenolate mofetil (1 g three times a day,
      days 0-28) and tacrolimus (0.03 mg/kg a day, titrated to a goal level of 8-12
      ng/mL, starting day -3 until day 180). Vorinostat (either 100 mg or 200 mg, twice
      a day) was initiated 10 days before haemopoietic stem-cell transplantation until
      day 100. The primary endpoint was the cumulative incidence of grade 2-4 acute
      GVHD by day 100. This trial is registered with ClinicalTrials.gov, number
      NCT00810602. FINDINGS: 50 patients were assessable for both toxic effects and
      response; eight additional patients were included in the analysis of toxic
      effects. All patients engrafted neutrophils and platelets at expected times after
      haemopoietic stem-cell transplantation. The cumulative incidence of grade 2-4
      acute GVHD by day 100 was 22% (95% CI 13-36). The most common non-haematological
      adverse events included electrolyte disturbances (n=15), hyperglycaemia (11),
      infections (six), mucositis (four), and increased activity of liver enzymes
      (three). Non-symptomatic thrombocytopenia after engraftment was the most common
      haematological grade 3-4 adverse event (nine) but was transient and all cases
      resolved swiftly. INTERPRETATION: Administration of vorinostat in combination
      with standard GVHD prophylaxis after related-donor reduced-intensity conditioning
      haemopoietic stem-cell transplantation is safe and is associated with a lower
      than expected incidence of severe acute GVHD. Future studies are needed to assess
      the effect of vorinostat for prevention of GVHD in broader settings of
      haemopoietic stem-cell transplantation. FUNDING: Merck, Leukemia and Lymphoma
      Society, National Institutes of Health, St Baldrick's Foundation, Michigan
      Institute for Clinical and Health Research.

PMID- 24295576
TI  - Vascular endothelial growth factor promotes peripheral nerve regeneration after
      sciatic nerve transection in rat.
AB  - OBJECTIVE: To evaluate the local effect of vascular endothelial growth factor
      (VEGF) on transected sciatic nerve regeneration. METHODS: Sixty male white Wistar
      rats were divided into four experimental groups randomly (n equal to 15). In
      transected group the left sciatic nerve was transected and the stump was fixed to
      adjacent muscle. In treatment group the defect was bridged using a silicone graft
      filled with 10 microlitre VEGF. In silicone group the graft was filled with
      phosphate-buffered saline. In sham-operated group the sciatic nerve was exposed
      and manipulated. Each group was subdivided into three subgroups with five animals
      in each and nerve fibers were studied 4, 8 and 12 weeks after operation. RESULTS:
      Behavioral test, functional study of sciatic nerve, gastrocnemius muscle mass and
      morphometric indices confirmed a faster recovery of regenerated axons in VEGF
      group than in silicone group (P less than 0.05). In immunohistochemical
      assessment, reactions to S-100 in VEGF group were more positive than that in
      silicone group. CONCLUSION: Local administration of VEGF will improve functional
      recovery and morphometric indices of sciatic nerve.

PMID- 24295577
TI  - Ectopic major transplantation for salvage of upper and lower extremity
      amputations.
AB  - OBJECTIVE: Ectopic tissue transplantation is not a new idea. Godina and his
      colleagues pioneered this method in the 1980s. This method is a last resort
      method of preserving an amputated body part, which consists of banking the
      amputated segment in an ectopic area and returning it to its native place at a
      later date. In this article we present our experience with this demanding
      procedure. METHODS: Debridement was the mainstay of this procedure. The stump and
      amputated part are carefully debrided and the stump was either closed primarily
      or covered by a flap. The amputated part was transplanted to one of several
      banking sites in the body and at a later date it will be transferred to its
      native site in an elective setting. RESULTS: Seven patients meeting the set
      criteria for ectopic transplantation were enrolled in this study. The overall
      success rate was about 70%, lower than expected but these are cases of severe
      crush injury. Although the functional recovery of these patients are very low,
      all of the successful cases except one could find a job as a janitor or light
      manual worker. No patient could return to his previous job. CONCLUSION: Ectopic
      transplantation of body parts is an accepted method of treatment of severely
      crushed extremity or finger injuries. In our country an amputee has very little
      chance of finding a job instead a disabled person can. In addition in Iran
      cultures amputation is seen as punishment of either the God or the society, so it
      is not well accepted and many patients persist on saving the limb even with no
      functional recovery. None of our successful cases could return to his previous
      occupation but almost all of them could find a job as janitors or light manual
      workers.

PMID- 24295578
TI  - Multimodal endovascular treatment for traumatic carotid-cavernous fistula.
AB  - OBJECTIVE: To present our experience in treating traumatic carotid-cavernous
      fistula (TCCF) by multimodal endovascular treatment. METHODS: The management of
      28 patients with TCCF between January 2004 and October 2012 in our hospital was
      retrospectively analyzed. According to imaging charateristics, 24 cases were
      categorized into Type I, 3 Type II and 1 Type III. Totally 30 endovascular
      treatments were performed: Type I TCCFs were obliterated via transvenous approach
      (7/25), or transarterial approach (18/25) including 6 by detachable balloon
      occlusion, 6 by microcoil embolization, 3 by Hyperglide balloon-assisted coil
      embolization and 3 by a combination of detachable balloon and coil embolization.
      Two patients were treated with closure of internal carotid artery (ICA). Type II
      TCCFs were treated with transvenous embolotherapy (2/3) or carotid artery
      compression therapy (1/3). The Type III patient underwent detachable balloon
      embolization. RESULTS: Immediate postoperative angiography showed recovery in 26
      cases. One recurrent TCCF was found 2 weeks after detachable balloon
      embolization, and then re-obliterated by transarterial coils. Reexamination found
      balloon deflation and fistula recanalization in 1 patient one month after
      combination of detachable balloons and coil embolization, which was cured by a
      second treatment via transvenous approach. The immediate angiography revealed
      residual blood flow in 4 patients. Among them, 2 patients with delayed symptoms
      at follow-up needed a second treatment, 1 patient recovered after carotid artery
      compression therapy, and the remaining patient's symptoms disappeared on digital
      subtraction angiography at five-month follow-up. CT angiography revealed anterior
      communicating artery aneurysm in the patient who was treated with closure of ICA
      4 years later. CONCLUSION: According to results of images, characteristics of the
      fistula and type of drainage, proper treatment approach and embolic material can
      maximally heal pathological changes, retain the ipsilateral ICA patency and
      reduce long-term complications.

PMID- 24295579
TI  - Osteosynthesis with long volar locking plates for metaphyseal-diaphyseal
      fractures of the distal radius.
AB  - OBJECTIVE: Metaphyseal-diaphyseal fractures of the distal radius are a major
      treatment dilemma and orthopaedic surgeons have to pay due consideration to
      restoration of anatomy of distal radius together with rotation of the radial
      shaft and maintenance of radial bow and interosseous space. We performed this
      study to evaluate the clinic-radiological outcome of metaphyseal-diaphyseal
      fractures of the distal radius treated with long volar locking plates. METHODS:
      This prospective study involved 27 patients (22 males and 5 females) with
      metaphyseal-diaphyseal fracture of the distal radius. Their mean age was (30.12+/
      11.48) years (range 19-52 years) and the follow-up was 26.8 months (range 22-34
      months). All patients underwent open reduction and internal fixation with a long
      volar locking plate. According to AO/OTA classification, there were 7 type A3, 13
      type C2 and 7 type C3 fractures. Subjective assessment was done based on the
      disabilities of the arm, shoulder and hand (DASH) questionnaire. Functional
      evaluation was done by measuring grip strength and range of motion around the
      wrist and the radiological determinants included radial angle, radial length,
      volar angle and ulnar variance. The final assessment was done according to
      Gartland and Werley scoring system. RESULTS: Postoperative radiological
      parameters were well maintained throughout the trial, and there was significant
      improvement in the functional parameters from 6 weeks to final follow-up. The
      average DASH scores improved from 37.5 at 6 weeks to 4.2 at final follow-up.
      Final assessment using Gartland and Werley scoring system revealed 66.67% (n
      equal to 18) excellent and 33.33% (n equal to 9) good results. There was one case
      of superficial infection which responded to antibiotics and another carpel tunnel
      syndrome which was managed conservatively. CONCLUSION: Volar locking plate
      fixation for metaphyseal-diaphyseal fractures of distal radius is associated with
      excellent to good functional outcome, early rehabilitation and minimal
      complications.

PMID- 24295580
TI  - A Galeazzi-variant type fracture-dislocation in adults.
AB  - OBJECTIVE: Fracture of either radius or ulna with a dislocation either at the
      proximal or distal radioulnar joint (DRUJ) is not a common injury and is
      inherently unstable. Here we report a case series, with both-bone forearm
      fractures associated with dislocation of DRUJ, as a Galeazzi-variant type
      fracture-dislocation, and try to analyze this injury pattern. METHODS: The study
      was based on 6 patients having Galeazzi-variant type fracture-dislocation of
      different age (20 to 45 years). All fractures were closed type. Two fractures
      involved the same level and three fractures were at different levels of radius
      and ulna shaft. After thorough examination and investigations they were treated
      with limited contact dynamic compression plate without additional fixation for
      DRUJ. RESULTS: All cases were followed up for 24 weeks. The maximum incidence
      occurred in age group between 31 and 40 years. All the fractures of both radius
      and ulna were united in average time of 12 weeks. Range of motion of wrist and
      elbow, supination and pronation at final follow-up were normal. There was no
      subsequent re-subluxation or dislocation of the DRUJ in any of the cases.
      CONCLUSION: Galeazzi variant in adult is a new undescribed pattern of forearm
      with wrist injury. Stable open reduction and internal fixation of both-bone
      forearm fractures is mandatory, followed by 3 to 4 weeks of immobilization in a
      cast for the healing of disrupted DRUJ.

PMID- 24295581
TI  - Pattern of ocular trauma among the elderly in Kashan, Iran.
AB  - OBJECTIVE: Ocular trauma is a common cause of visual impairment and accounts for
      38% to 52% of all patients presenting as ophthalmic accident and emergency cases
      to the hospital. The purpose of this study is to describe the pattern of ocular
      injuries that leads to hospitalization in the elderly in Kashan, Iran. METHODS:
      In the retrospective consecutive case series, a total of 94 geriatric patients
      (larger than or equal to 65 years) who admitted and underwent management for
      ocular trauma from April 2001 to March 2011 at Matini Hospital of Kashan, the
      only center of eye surgery in the region of Kashan, were reviewed. The items
      include age, sex, injury mechanism, site and extent of damage, presenting and
      final best corrected visual acuity at least 3 months after trauma, which were
      reviewed and analyzed with SPSS software. RESULTS: During the 10 years, 94 eyes
      of 94 patients with ocular trauma were included. Mean age of patients was (77.5+/
      5.1) years (range 65 to 102 years). Male to female ratio was 2.76. The mechanism
      of ocular injury included sharp trauma in 56 patients (59.6%) and blunt in 38
      patients (40.4%). Trauma occurred mostly in males (69 patients, 73.4%) and at the
      work place (38 patients, 40.4%). On admission the visual acuity in 50 patients
      (53.2%) with damaged eyes was light perception to hand motion. While the final
      best corrected visual acuity in 36 patients (38.3%) was better than hand motion.
      CONCLUSION: Ocular trauma is a serious cause of visual impairment in the elderly.
      Appropriate and timely management may improve their visual prognosis.

PMID- 24295582
TI  - Accuracy of chest radiography versus chest computed tomography in hemodynamically
      stable patients with blunt chest trauma.
AB  - OBJECTIVE: Thoracic injuries are responsible for 25% of deaths of blunt traumas.
      Chest X-ray (CXR) is the first diagnostic method in patients with blunt trauma.
      The aim of this study was to detect the accuracy of CXR versus chest computed
      tomograpgy (CT) in hemodynamically stable patients with blunt chest trauma.
      METHODS: Study was conducted at the emergency department of Sina Hospital from
      March 2011 to March 2012. Hemodynamically stable patients with at least 16 years
      of age who had blunt chest trauma were included. All patients underwent the same
      diagnostic protocol which consisted of physical examination, CXR and CT scan
      respectively. RESULTS: Two hundreds patients (84% male and 16% female) were
      included with a mean age of (37.9+/-13.7) years. Rib fracture was the most common
      finding of CXR (12.5%) and CT scan (25.5%). The sensitivity of CXR for
      hemothorax, thoracolumbar vertebra fractures and rib fractures were 20%, 49% and
      49%, respectively. Pneumothorax, foreign body, emphysema, pulmonary contusion,
      liver hematoma and sternum fracture were not diagnosed with CXR alone.
      CONCLUSION: Applying CT scan as the first-line diagnostic modality in
      hemodynamically stable patients with blunt chest trauma can detect pathologies
      which may change management and outcome.

PMID- 24295583
TI  - Outcome of open reduction and internal fixation of intraarticular calcaneal
      fracture fixed with locking calcaneal plate.
AB  - OBJECTIVE: Debate continues regarding the management of calcaneal fractures,
      between open reduction and internal fixation and closed treatment. Hence we aim
      at evaluating the radiological and functional outcomes of open reduction and
      internal fixation in displaced joint depression type of calcaneal fractures fixed
      with locking calcaneal plate. METHODS: In this series, 28 patients (26 unilateral
      and 2 bilateral) with joint depression type of calcaneal fractures as per Essex
      Lopresti classification system were operated on with locking calcaneal plate
      within 3 weeks of injury. Patients were evaluated in terms of associated injuries
      and X-rays of anteroposterior, lateral and axial views of the calcaneum. CT scan
      was done to assess the amount of comminution and articular depression. Patients
      were followed up clinically and radiologically at least for 1 year. Radiological
      assessment was done by Bohler's angle and Gissane's angle along with measurement
      of calcaneal height and width. Functional outcome was assessed using the American
      Orthopaedics Foot and Ankle Society (AOFAS) scale. RESULTS: At average follow-up
      of 14.5 months, average AOFAS score was 86.3 (range 66 to 97), with 86% having
      excellent to good results and 2 (7.7%) and 1 (3.7%) having fair and poor results
      respectively. All patients had stable ankle joint with all having dorsiflexion
      and plantar flexion more than 30 degrees. Average subtalar range of motion was 17
      degrees The mean Bohler's angle, mean Gissane's angle, calcaneal height and width
      were 25.47 degrees 121.3 degrees 4.32 cm and 3.81 cm respectively at final follow
      up. Three patients had flap necrosis at incision site and one had superficial and
      deep infection. Subtalar arthritis was seen in 5 patients, whereas sural nerve
      hypoaesthesia in 1 patient. None of the patients had compartment syndrome, heel
      pad problems, peroneal tendinitis, reflex sympathetic dystropy or implant
      failure. CONCLUSION: Open reduction and internal fixation with locking calcaneal
      plate gives sound functional outcome, i.e. restoring anatomically reconstruction
      of height, width, Bohler's and Gissiane's angles of the calcaneum, and allowing
      early mobilization.

PMID- 24295584
TI  - Results of surgically treated talar fractures.
AB  - OBJECTIVE: Talar fractures present a great challenge to surgeons due to poor
      treatment outcome and high incidence of sequelae. The purpose of this study was
      to report the surgical treatment outcome of displaced talar fractures treated by
      internal fixation. METHODS: A total of 30 patients with a mean age of 38 years
      presenting with talar body or neck fractures were studied retrospectively to
      assess postoperative outcome based on American Orthopaedic Foot and Ankle Society
      Ankle-Hindfoot scale. RESULTS: Postoperatively, malunion was found in 18 cases,
      infection in 5 cases and avascular necrosis in 12 cases. There were 12 cases with
      subtalar arthritis and 18 cases with both subtalar and malleolar arthritis. The
      average score of questionnaire was 64+/-12. Functional score was 53+/-15 and pain
      score was 65+/-13. Range of motion failure was detected as 15+/-4. CONCLUSION:
      Talar injuries can compromise motion of the foot and ankle and result in poor
      prognosis on long-term evaluation. Late complications subsequent to surgically
      treated talar body fractures are inevitable, and patients are supposed to be
      counseled about the adverse outcome.

PMID- 24295585
TI  - Combined radial and median nerve injury in diaphyseal fracture of humerus: a case
      report.
AB  - Radial nerve palsy is the most common neurological involvement in humeral shaft
      fractures. But combined radial and median nerve injury in a closed diaphyseal
      fracture of the humerus is rare. Combined injury to both radial and median nerve
      can cause significant disability. A detailed clinical examination is therefore
      necessary following humeral shaft fractures. We report a patient with closed
      diaphyseal humeral fracture (AO 12A-2.3) together with radial and median nerve
      palsy, its management and review of the literature. As the patient had two nerves
      involved, surgical exploration was planned. Fracture was reduced and fixed with a
      4.5 mm narrow dynamic compression plate. There was no external injury to both
      radial and median nerves on surgical exploration. Neurological recovery started
      at 3 weeks' follow-up. Complete recovery was seen at 12 weeks. Careful clinical
      examination is of the utmost importance in early diagnosis of combined nerve
      injuries, which allows better management and rehabilitation of the patient. 

PMID- 24295586
TI  - Iatrogenic aortic pseudoaneurysm following anterior thoracic spine surgery
      masquerading as chronic infection.
AB  - Late vascular complications involving aorta are rare but devastating adversities
      following anterior thoracic spine operations are present. The current article
      describes our experience with one such patient who had an iatrogenic
      pseudoaneurysm of the thoracic aorta, mimicking infection. The patient was
      treated successfully following concomitant efforts by multidisciplinary experts
      with shunting. We wish to highlight upon the significance of recognizing the
      possible sinister consequences of a dangerously prominent spinal implant and the
      role of a suspicious surgeon in identifying these menacing complications at the
      right time. 

PMID- 24295587
TI  - Iatrogenic brachial artery injury during anterolateral plating of humeral shaft
      fracture.
AB  - There are several well defined indications for surgical management of humeral
      shaft fractures. Operative procedures on the humerus are associated with their
      own complications. Iatrogenic brachial artery injury as a complication of humeral
      shaft plating has not been reported previously. We report a case of a 48 years
      old female, who received operation at a district hospital and was referred to us
      when the surgeon could not palpate the pulse. CT angiogram showed that there was
      segmental non-opacification of the brachial artery. There was distal reformation
      and the thrombosis was decided to be managed conservatively. We believe that the
      arterial injury was a result of improper surgical technique and the segmental
      block might be due to improper use of plate holding forceps. This case report
      makes us aware of a rare complication of operative management of humeral shaft
      fractures and that basic principles of surgery must be always followed to prevent
      such injuries.

PMID- 24295588
TI  - Missed posterior shoulder dislocation with malunited proximal humerus fracture.
AB  - Posterior dislocation of the shoulder may be missed or neglected at initial
      presentation especially in developing countries. We present a case of 40-year-old
      Indian man who had 3-month missed posterior dislocation of the right shoulder
      along with malunited fracture of the anatomical neck of the humerus. Open
      reduction and stabilization with modified McLaughlin procedure was performed.
      Rotational osteotomy of proximal humerus had to be performed as supplementary
      procedure to keep the humeral head stable in glenoid cavity during functional
      range of movements. The patient had excellent result of the shoulder at 3 years
      follow-up. 

PMID- 24295589
TI  - Bilateral traumatic proximal humerus fractures managed by open reduction and
      internal fixation with locked plates.
AB  - Fractures of the proximal humerus are uncommon in young patients. Although
      bilateral fracture of proximal humerus itself is rare, association with epilepsy
      and electrocution is frequent. Only one case of traumatic bilateral proximal
      humerus fracture has been reported in the literature. We report a rare case of
      bilateral traumatic displaced proximal humerus fractures in a 40 years old male
      patient, which was treated by means of open reduction and internal fixation with
      proximal humerus locked pates on both sides and obtained a good functional
      outcome.

PMID- 24295590
TI  - Co-administration of dual-targeting nanoparticles with penetration enhancement
      peptide for antiglioblastoma therapy.
AB  - Chemotherapy is an indispensable auxiliary treatment for glioma but highly
      limited by the existence of both blood-brain barrier (BBB) and blood-brain tumor
      barrier (BBTB). The dysfunctional brain tumor blood vessels and high interstitial
      pressure in glioma also greatly hindered the accumulation and deep penetration of
      chemotherapeutics into the glioma. Lactoferrin (Lf), with its receptor
      overexpressed on both the brain endothelial cells and glioma cells, was here
      functionalized to the surface of poly(ethylene glycol)-poly(lactic acid)
      nanoparticles to mediate BBB/BBTB and glioma cell dual targeting. tLyP-1, a tumor
      homing peptide, which contains a C-end Rule sequence that can mediate tissue
      penetration through the neuropilin-1-dependent internalization pathway, was
      coadministrated with Lf-functionalized nanoparticles (Lf-NP) to enhance its
      accumulation and deep penetration into the glioma parenchyma. Enhanced cellular
      association in both BCEC and C6 cells, increased cytotoxicity of the loaded
      paclitaxel, and deep penetration in the 3D glioma spheroids was achieved by Lf
      NP. Following coadministration with tLyP-1, the functionalized nanoparticles
      obtained improved tumor targeting, glioma vascular extravasation, and antiglioma
      efficacy. The findings here suggested that the strategy by coadministrating
      BBB/BBTB and glioma cells dual-targeting nanocarriers with a tumor penetration
      enhancement peptide represent a promising platform for antiglioma drug delivery. 

PMID- 24295592
TI  - WITHDRAWN: A critical review of recycling rare-earths from waste phosphor.
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- 24295591
TI  - Dendritic cells play a role in host susceptibility to Cryptosporidium parvum
      infection.
AB  - Our previous studies have described dendritic cells (DCs) to be important sources
      of Th1 cytokines such as IL-12 and IL-2 in vitro, following stimulation with
      Cryptosporidium parvum antigens. We further established the role of DCs during
      cryptosporidiosis using a diphtheria toxin promoter regulated transgenic CD11c
      DTR/EGFP mouse model. In vivo depletion of CD11c(+) cells in CD11c-DTR-Tg mice
      significantly increased susceptibility to C. parvum infection. Adoptive transfer
      of unstimulated or antigen stimulated DCs into CD11c(+) depleted CD11c-DTR-Tg
      mice resulted in an early decrease in parasite load at 4 days post infection.
      However, this response was transient since parasite load increased in mice
      engrafted with either unstimulated DCs or DCs stimulated with solubilized antigen
      by 6 days post infection. In contrast, in mice engrafted with DCs stimulated with
      live sporozoites, parasite load remained low during the entire period, suggesting
      the development of a more effective and sustained response. A corresponding
      increase in IFN-gamma expression in T cells from spleen and mesenteric lymph
      nodes was also noted. Consistent with the in vivo engraftment study, DCs that are
      pulsed with live sporozoites in vitro and co-cultured with CD4(+) and CD8(+) T
      cells produced higher IFN-gamma levels. Our study establishes the importance of
      DCs in susceptibility to infection by C. parvum and as important mediators of
      immune responses. 

PMID- 24295593
TI  - A resourceful giant: APMV is able to interfere with the human type I interferon
      system.
AB  - Acanthamoeba polyphaga mimivirus (APMV) is a giant, double-stranded virus of the
      Mimiviridae family that was discovered in 2003. Recent studies have shown that
      this virus is able to replicate in murine and human phagocytes and might be
      considered a putative human pathogen that causes pneumonia. However, there is
      little data regarding APMV and its host defense relationship. In the present
      study, we investigated how some components of the interferon (IFN) system are
      stimulated by APMV in human peripheral blood mononuclear cells (PBMCs) and how
      APMV replication is affected by IFN treatment. Our results demonstrated that APMV
      is able to replicate in human PBMCs, inducing type I Interferons (IFNs) but
      inhibiting interferon stimulated genes (ISG) induction by viroceptor and STAT-1
      and STAT-2 dephosphorylation independent mechanisms. We also showed that APMV is
      resistant to the antiviral action of interferon-alpha2 (IFNA2) but is sensitive
      to the antiviral action of interferon-beta (IFNB1). Our results demonstrated the
      productive infection of professional phagocytes with APMV and showed that this
      virus is recognized by the immune system of vertebrates and inhibits it. It
      provides the first data regarding APMV and the IFN system interaction and raise
      new and relevant evolutional questions about the relationship between APMV and
      vertebrate hosts.

PMID- 24295594
TI  - Physiological disturbance of the Manila clam, Ruditapes philippinarum, by altered
      environmental conditions in a tidal flat on the west coast of Korea.
AB  - To examine the influence of habitat alteration by tideflat reclamation on the
      physiological ecology of Ruditapes philippinarum, seasonal variations in its
      condition, gross biochemical composition, and reproductive cycle were compared
      for a yearly cycle between a reclaimed flat (Gomsohang, GS) and a natural flat
      (Hajun, HJ) in Gomso Bay, Korea. Concentrations of chlorophyll a and seston (as
      well as its energy value as food available to the clam) were consistently higher
      at HJ than at GS. Condition, dry tissue weight, and energy reserves (proteins and
      carbohydrates) of the clams were much higher at HJ than at GS during spring
      summer, when fast growth and gametogenic development occur. Furthermore, their
      spring gametogenic development and spawning were advanced at HJ compared with GS.
      Our results suggest that the Manila clam encounters nutritionally stressful
      environmental conditions in altered habitats after tideflat reclamation that lead
      to lowered nutrient accumulation and a changing reproductive cycle. 

PMID- 24295595
TI  - Assessment of TBT and organic booster biocide contamination in seawater from
      coastal areas of South Korea.
AB  - Seawater samples from major enclosed bays, fishing ports, and harbors of Korea
      were analyzed to determine levels of tributyltin (TBT) and booster biocides,
      which are antifouling agents used as alternatives to TBT. TBT levels were in the
      range of not detected (nd) to 23.9 ng Sn/L. Diuron and Irgarol 1051, at
      concentration ranges of 35-1360 ng/L and nd to 14 ng/L, respectively, were the
      most common alternative biocides present in seawater, with the highest
      concentrations detected in fishing ports. Hot spots were identified where TBT
      levels exceeded environmental quality targets even 6 years after a total ban on
      its use in Korea. Diuron exceeded the UK environmental quality standard (EQS)
      value in 73% of the fishing port samples, 64% of the major bays, and 42% of the
      harbors. Irgarol 1051 levels were marginally below the Dutch and UK EQS values at
      all sites.

PMID- 24295596
TI  - Comparing plastic ingestion in juvenile and adult stranded short-tailed
      shearwaters (Puffinus tenuirostris) in eastern Australia.
AB  - Numerous species of seabirds have been shown to ingest anthropogenic debris, but
      few studies have compared ingestion rates between adults and juveniles of the
      same species. We investigated marine debris ingestion by short-tailed shearwaters
      (Puffinus tenuirostris) obtained through two stranding events on North Stradbroke
      Island, Australia in 2010 (n=102; adult) and 2012 (n=27; juveniles). Necropsies
      were conducted and solid contents found in guts were categorized into type and
      color. Over 67% of birds ingested anthropogenic debris: 399 pieces of debris were
      identified. We found no significant relationship between body condition of birds
      which had ingested anthropogenic debris and those that had not. Juvenile birds
      were more likely to ingest debris than were adult birds and juveniles ingested
      significantly more pieces of debris than did adults. Male and female birds
      ingested similar amounts and weights of debris. To determine if P. tenuirostris
      actively selects for certain types of debris, we compared ingested debris to
      samples obtained from boat-based tows. Significant differences were found,
      suggesting that the birds select for hard plastic, rubber and balloons. 

PMID- 24295597
TI  - The views and attitudes of health professionals providing antenatal care to women
      with a high BMI: a qualitative research study.
AB  - BACKGROUND: The prevalence of overweight and obesity is increasing amongst women
      of child bearing age. The objective of this study was to investigate the views
      and attitudes of providers of antenatal care for women who have a body mass index
      (BMI) of 30 kg/m(2) and over. METHODS: A qualitative study using focus groups was
      undertaken within the department of obstetrics and gynaecology at a large
      teaching hospital in south-eastern Australia. Three focus group discussions were
      held. One with hospital midwives (n=10), one with continuity of care midwives
      (n=18) and one with obstetricians (n=5). Data were analysed using Interpretative
      Phenomenological Analysis (IPA). FINDINGS: Six dominant themes emerged: (1)
      obesity puts the health of mothers, babies and health professionals at risk; (2)
      overweight and obesity has become the norm; (3) weighing women and advising about
      weight gain is out of fashion; (4) weight is a sensitive topic to discuss; (5)
      there are significant barriers to weight control in pregnancy; and (6) health
      professionals and women need to deal with maternal obesity. These themes are
      drawn together to form a model representing current health care issues for these
      women. CONCLUSION: Health professionals, who have a high BMI, can find it
      difficult to discuss obesity during antenatal visits with obese women. Specialist
      dietary interventions and evidence based guidelines for working with child
      bearing women is seen as a public health priority by health care professionals.

PMID- 24295598
TI  - An emerging model of maternity care: smartphone, midwife, doctor?
AB  - BACKGROUND: Mobile technology in the form of the smartphone is widely used,
      particularly in pregnancy and they are an increasing and influential source of
      information. AIM: To describe the diverse nature of pregnancy related
      applications (apps) for the smartphone and to flag that these apps can
      potentially affect maternity care and should be considered in future planning of
      care provision. METHODS: The 2 smartphone platforms, Apple and Android, were
      searched for pregnancy related apps and reviewed for their purpose and
      popularity. FINDINGS: iTunes and Google Play returned 1059 and 497 pregnancy
      related apps respectively. Forty percent of the apps were informative, 13%
      interactive, 19% had features of a medical tool and 11% were social media apps.
      By far the most popular apps, calculated as the number of reviews multiplied by
      average reviewer rating, were those with interactive features. DISCUSSION: The
      popularity of pregnancy-related apps could indicate a shift towards patient
      empowerment within maternity care provision. The traditional model of 'shared
      maternity care' needs to accommodate electronic devices into its functioning.
      Reliance on healthcare professionals may be reduced by the availability of
      interactive and personalised information delivered via a smartphone. This
      combined with the fact that smartphones are widely used by many women of
      childbearing age, has the potential to modify maternity care and experiences of
      pregnancy. Therefore it is important that healthcare professionals and policy
      makers are more aware of these new developments, which are likely to influence
      healthcare and alter health-seeking behaviour. In addition healthcare
      professionals need to consider whether to discuss the use of apps in pregnancy
      with the women in their care.

PMID- 24295599
TI  - Exosomes from myeloid-derived suppressor cells carry biologically active
      proteins.
AB  - Myeloid-derived suppressor cells (MDSC) are present in most cancer patients where
      they inhibit natural anti-tumor immunity and are an obstacle to anti-cancer
      immunotherapies. They mediate immune suppression through their production of
      proteins and soluble mediators that prevent the activation of tumor-reactive T
      lymphyocytes, polarize macrophages toward a tumor-promoting phenotype, and
      facilitate angiogenesis. The accumulation and suppressive potency of MDSC is
      regulated by inflammation within the tumor microenvironment. Recently exosomes
      have been proposed to act as intercellular communicators, carrying active
      proteins and other molecules between sender cells and receiver cells. In this
      report we describe the proteome of exosomes shed by MDSC induced in BALB/c mice
      by the 4T1 mammary carcinoma. Using bottom-up proteomics, we have identified 412
      proteins. Spectral counting identified 63 proteins whose abundance was altered >2
      fold in the inflammatory environment. The pro-inflammatory proteins S100A8 and
      S100A9, previously shown to be secreted by MDSC and to be chemotactic for MDSC,
      are abundant in MDSC-derived exosomes. Bioassays reveal that MDSC-derived
      exosomes polarize macrophages toward a tumor-promoting type 2 phenotype, in
      addition to possessing S100A8/A9 chemotactic activity. These results suggest that
      some of the tumor-promoting functions of MDSC are implemented by MDSC-shed
      exosomes. 

PMID- 24295600
TI  - The risk of Bipolar Disorders in Multiple Sclerosis.
AB  - BACKGROUND: The aim was to determine the risk of Mood Disorders (MD),
      particularly Bipolar Disorders (BD), in Multiple Sclerosis (MS) using
      standardized psychiatric diagnostic tools. METHODS: Case-control study. CASES:
      201 consecutive-patients with MS. CONTROLS: 804 sex- and age-matched subjects
      without MS, randomly selected from a database concurrently used for an
      epidemiological study on the MD prevalence in the community. Psychiatric
      diagnoses according to DSM-IV were determined by physicians using structured
      interview tools (ANTAS-SCID). RESULTS: Compared to controls, MS patients had a
      higher lifetime prevalence of DSM-IV Major Depressive Disorders (MDD; P<0.0001),
      BD I (P=0.05), BD II (P<0.0001) and Cyclothymia (P=0.0001). As people with MS had
      a higher risk of depressive and bipolar spectrum disorders, ratio MDD/bipolar
      spectrum disorders was lower among cases (P<0.005) indicating a higher
      association with Bipolar Spectrum Disorders and MS. LIMITATIONS: MS diagnosis was
      differently collected in cases and controls. Even if this might have produced
      false negatives in controls, it would have reinforced the null hypothesis of no
      increased risk for MD in MS; therefore, it does not invalidate the results of the
      study. CONCLUSIONS: This study was the first to show an association between BD
      and MS using standardized diagnostic tools and a case-control design. The results
      suggest a risk of under-diagnosis of BD (particularly type II) in MS and caution
      in prescribing ADs to people with depressive episodes in MS without prior
      excluding BD. The association between auto-immune degenerative diseases (like MS)
      and BD may be an interesting field for the study of the pathogenic hypothesis.

PMID- 24295601
TI  - Frontal white matter alterations are associated with executive cognitive function
      in euthymic bipolar patients.
AB  - BACKGROUND: Bipolar affective disorder (BD) is often associated with cognitive
      dysfunction in executive domains. However the biological underpinnings of
      cognitive deficits in BD are not sufficiently understood. A growing body of
      evidence indicates a loss of microstructural integrity in various white matter
      (WM) fiber tracts in BD. The aim of the current study was to assess potential
      links between WM structural abnormalities and cognitive performance in euthymic
      middle-aged BD patients (n=30) and matched healthy controls (n=32). METHODS:
      Diffusion tensor imaging (DTI) data was carried out with both voxelwise (tract
      based spatial statistics, TBSS) and region-of-interest (ROI) based analysis. We
      compared multiple indices of diffusion including fractional anisotropy (FA),
      radial (DR), axial (DA) and mean diffusivities (MD). RESULTS: Increased mean
      diffusivity was found in the fornix, anterior thalamic radiation, splenium and
      the truncus of the corpus callosum in BD patients compared with controls. These
      diffusion changes were significantly associated with poorer performance in
      executive tasks in BD patients. CONCLUSIONS: Our results indicate a direct link
      between executive cognitive functioning and abnormal WM microstructural integrity
      of fronto-limbic tracts in remitted BD patients, and add evidence to the neuronal
      disruption that underlies the residual symptomatology of BD.

PMID- 24295602
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy without anterior temporal pole involvement: a case report.
AB  - The location of white matter lesions, especially in the anterior temporal poles
      (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-year
      old man with CADASIL who developed migraine with atypical aura, silent lacunar
      infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence
      of migraine with aura in subjects with CADASIL is several times greater than that
      in the general population. Particularly in patients with CADASIL, the aura is
      often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should
      be considered in patients with lacunar infarcts, leukoencephalopathy, and
      migraine with atypical aura, even in the absence of white matter lesion in the
      ATPs. 

PMID- 24295603
TI  - Predictive value of plasma (D)-dimer levels for cancer-related stroke: a 3-year
      retrospective study.
AB  - BACKGROUND: Cerebrovascular disease is the second leading cause of central
      nervous system pathology in cancer patients. Cancer-associated hypercoagulation
      plays an important role in cancer-related stroke. The present study aims to test
      whether plasma d-dimer levels could predict comorbid malignancy in patients with
      ischemic stroke. METHODS: Five hundred sixteen stroke patients with measured d
      dimer levels and who were consecutively admitted to our stroke center from 2009
      to 2012 were included. Cancer status was determined by medical chart, and 59
      patients were identified to have active cancer. An additional 48 cancer patients
      with stroke were identified from the hospital database. Several d-dimer cutoff
      levels were used to predict cancer-related stroke. RESULTS: Stroke patients with
      active cancer had significantly higher d-dimer levels than those without cancer
      (P < .001). The average d-dimer level in stroke patients without cancer was .66
      +/- 1.83 mg/L, whereas the levels for active cancer patients from the stroke
      center and hospital database were 5.70 +/- 9.63 mg/L and 10.47 +/- 12.31 mg/L,
      respectively. When using d-dimer of .55 mg/L or more and multiple territory
      infarctions as criteria, the specificity and positive predictive value (PPV) for
      cancer-related stroke were 99.7% and 92.9%, respectively. When using d-dimer of
      5.5 mg/L or more as the cutoff value, the test had a high specificity and PPV
      regardless the brain magnetic resonance imaging (MRI) findings. Six stroke
      patients fitting our criteria were confirmed to have occult malignancy after
      comprehensive cancer survey. CONCLUSIONS: Extraordinary high d-dimer levels or
      combining d-dimer and MRI findings may be used as a screening tool to detect
      malignancy in stroke patients.

PMID- 24295604
TI  - Doctors fear that new CCG funding formula will downplay deprivation.

PMID- 24295605
TI  - Pediatric sepsis. Foreword.

PMID- 24295606
TI  - Definitions and pathophysiology of sepsis.
AB  - Mortality rates for sepsis and septic shock have not improved in the past decade.
      The Surviving Sepsis Campaign (SSC) guidelines released in 2012 emphasize early
      recognition and treatment of sepsis, in an effort to reduce the burden of sepsis
      worldwide. This series of review articles will discuss the pathophysiology of
      sepsis; comorbidities, such as multiorgan dysfunction syndrome (MODS), acute
      respiratory distress syndrome (ARDS), and endocrine issues; and finally,
      management of sepsis and septic shock. 

PMID- 24295607
TI  - Stress response in critical illness.
AB  - Sepsis brings about neuroendocrine dysfunction in children that differs
      significantly from that of adults and can thus be difficult to interpret and
      manage. Aggressive treatment of sepsis with appropriate and judicious use of
      antibiotics remains a top priority. Strict glycemic control in children has been
      associated with significant risk of hypoglycemia, which may independently
      contribute to morbidity and mortality. Timely initiation of hydrocortisone in
      persistently hypotensive children with fluid-refractory, catecholamine-resistant
      shock is controversial, but its use in children with suspected or proven adrenal
      insufficiency is suggested. Fluid and electrolyte abnormalities must be
      corrected. Treatment of thyroid dysfunction has been shown to be beneficial in
      certain specific populations but cannot be extrapolated to all septic patients
      with the current available data. 

PMID- 24295608
TI  - Multiple organ dysfunction syndrome.
AB  - Initially known as multiple system organ failure, the term multiple organ
      dysfunction syndrome (MODS) was first described in the 1960s in adults with
      bleeding, respiratory failure, and sepsis. It is defined as "the development of
      potentially reversible physiologic derangement involving two or more organ
      systems not involved in the disorder that resulted in ICU admission, and arising
      in the wake of a potentially life threatening physiologic insult."(3) There are
      many risk factors predisposing to MODS; however, the most common risk factors are
      shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune
      response, or immuneparalysis, in which the homeostasis between pro-inflammatory
      and anti-inflammatory reaction is lost is thought to be key in the development of
      MODS. The clinical course and evolution of MODS is dependent on a combination of
      acquired and genetic factors. There are several nonspecific therapies for the
      prevention and resolution of MODS, mostly care is supportive. Mortality from MODS
      in septic pediatric patients varies between 11% and 54%. 

PMID- 24295609
TI  - Acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is commonly associated with severe
      sepsis. While the criteria for diagnosis have evolved since the first description
      in 1967, the characteristics of hypoxemia, tachypnea, rapidly progressing acute
      respiratory failure, and poor lung compliance continue. Scoring systems have been
      developed in an effort to quantify the severity of lung injury, with the most
      recent being the Berlin Definition. This system attempts to define acute lung
      injury (ALI) and ARDS with more precision in terms of timing of disease onset,
      severity of disease, and chest radiograph findings. The number of reported cases
      of ALI/ARDS per year is lower in pediatric patients vs. adults; however,
      mortality rates continue to be high. Sepsis-related ARDS has a generally higher
      disease severity and poorer recovery period from lung injury with an increased
      mortality rate. ARDS results from an initial insult (direct and/or indirect)
      which triggers a series of cell-mediated responses leading to damage to the
      capillary endothelium, alveolar epithelium, and impaired fluid removal from the
      alveolar space. There is, however, gradual resolution of hypoxemia, lung
      function, and radiographic abnormalities in survivors of ARDS. Management of ARDS
      is mainly supportive with specific mechanical ventilation strategies and goal
      directed therapies. Prevention of ventilator-induced lung injury (VILI) has been
      demonstrated to have a positive impact on outcomes in patients with ARDS. 

PMID- 24295610
TI  - The management of sepsis.
AB  - Management of sepsis in the pediatric patient is guideline driven. The treatment
      occurs in two phases, the first hour being the most crucial. Initial treatment
      consists of timely recognition of shock and interventions aimed at supporting
      cardiac output and oxygen delivery along with administration of antibiotics. The
      mainstay of treatment for this phase is fluid resuscitation. For patients in whom
      this intervention does not reverse the shock medications to support blood
      pressure should be started and respiratory support may be necessary.
      Differentiation between warm and cold shock and risk factors for adrenal
      insufficiency will guide further therapy. Beyond the first hour of treatment
      patients may require intensive care unit care where invasive monitoring may
      assist with further treatment options should shock not be reversed in the initial
      hour of care. 

PMID- 24295611
TI  - Body mass index and early kidney function decline in young adults: a longitudinal
      analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) study.
AB  - BACKGROUND: Identifying potentially modifiable risk factors is critically
      important for reducing the burden of chronic kidney disease. We sought to examine
      the association of body mass index (BMI) with kidney function decline in a cohort
      of young adults with preserved glomerular filtration at baseline. STUDY DESIGN:
      Longitudinal cohort. SETTING & PARTICIPANTS: 2,839 black and white young adults
      with cystatin C-based estimated glomerular filtration rate
      (eGFRcys)>90mL/min/1.73m(2) taking part in the year-10 examination (in 1995-1996)
      of the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
      PREDICTOR: BMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and
      >=40.0kg/m(2). OUTCOMES: Trajectory of kidney function decline, rapid decline
      (>3% per year), and incident eGFRcys <60mL/min/1.73m(2) over 10 years of follow
      up. MEASUREMENTS: GFRcys estimated from the CKD-EPI (Chronic Kidney Disease
      Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years
      10, 15, and 20. RESULTS: At year 10, participants had a mean age of 35.1 years,
      median eGFRcys of 114mL/min/1.73m(2), and 24.5% had BMI>=30.0kg/m(2). After age
      30 years, average eGFRcys was progressively lower with each increment in BMI
      after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and
      physical activity. Higher BMI category was associated with successively higher
      odds of rapid decline (for 25.0-29.9, 30.0-39.9, and >=40.0kg/m(2), adjusted ORs
      were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67
      3.94], respectively). 18 participants (0.6%) had incident
      eGFRcys<60mL/min/1.73m(2). In unadjusted analysis, higher BMI category was
      associated with incident eGFRcys<60mL/min/1.73m(2) (for 25.0-29.9, 30.0-39.9, and
      >=40.0kg/m(2), ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and
      5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer
      significant. LIMITATIONS: Inability to describe kidney function before
      differences by BMI category were already evident. Absence of data for measured
      GFR or GFR estimated from serum creatinine level. CONCLUSIONS: Higher BMI
      categories are associated with greater declines in kidney function in a cohort of
      young adults with preserved GFR at baseline. Clinicians should vigilantly monitor
      overweight and obese patients for evidence of early kidney function decline.

PMID- 24295612
TI  - Developing a CKD registry in primary care: provider attitudes and input.
AB  - BACKGROUND: Chronic disease registries have been successful at promoting the
      delivery of guideline-concordant primary care for patients with diabetes and
      hypertension, but not for chronic kidney disease (CKD). To understand whether a
      registry could be designed to improve CKD management in primary care, we explored
      primary care provider attitudes about the benefits (or lack thereof) of a CKD
      registry compared with other chronic diseases and the key facilitators of
      successfully implementing a CKD registry in safety-net primary care. STUDY
      DESIGN: Qualitative, using semistructured interviews. SETTING & PARTICIPANTS: We
      conducted and recorded semistructured 1-hour interviews with medical directors
      and quality improvement champions from safety-net adult primary care clinics in
      San Francisco. ANALYTIC APPROACH: Recordings were transcribed and analyzed using
      a grounded theory approach until thematic saturation was achieved. RESULTS: 20
      primary care providers were interviewed. 4 themes relevant to the development of
      a successful CKD registry for safety-net primary care were identified: (1)
      provider beliefs that a CKD registry could aid in the delivery of team-based high
      quality CKD care; (2) clinic workflow redesign and staffing are key facilitators
      to successful implementation of a CKD registry; (3) unique complexities of CKD,
      such as varying etiologies, may limit the use of a CKD registry by nonphysicians;
      and (4) a CKD registry is aligned with current primary care priorities and health
      care delivery strategies. LIMITATIONS: Small sample size and reliance on
      clinician leaders within one health care delivery system. CONCLUSIONS: A CKD
      registry directed at the entire health care team, with the functionality to
      track, standardize, and enhance CKD care through decision support, has the
      potential to improve the management of CKD in safety-net primary care settings.
      These data directly informed the development of a CKD registry in these settings
      in San Francisco.

PMID- 24295613
TI  - Hemodialysis catheter care strategies: a cluster-randomized quality improvement
      initiative.
AB  - BACKGROUND: The prevalence of central venous catheters (CVCs) for hemodialysis
      remains high and, despite infection-control protocols, predisposes to bloodstream
      infections (BSIs). STUDY DESIGN: Stratified, cluster-randomized, quality
      improvement initiative. SETTING & PARTICIPANTS: All in-center patients with a CVC
      within 211 facility pairs matched by region, facility size, and rate of positive
      blood cultures (January to March 2011) at Fresenius Medical Care, North America.
      QUALITY IMPROVEMENT PLAN: Incorporate the use of 2% chlorhexidine with 70%
      alcohol swab sticks for exit-site care and 70% alcohol pads to perform "scrub the
      hubs" in dialysis-related CVC care procedures compared to usual care. OUTCOME:
      The primary outcome was positive blood cultures for estimating BSI rates.
      MEASUREMENTS: Comparison of 3-month baseline period from April 1 to June 30 and
      follow-up period from August 1 to October 30, 2011. RESULTS: Baseline BSI rates
      were similar (0.85 vs 0.86/1,000 CVC-days), but follow-up rates differed at
      0.81/1,000 CVC-days in intervention facilities versus 1.04/1,000 CVC-days in
      controls (P = 0.02). Intravenous antibiotic starts during the follow-up period
      also were lower, at 2.53/1,000 CVC-days versus 3.15/1,000 CVC-days in controls (P
      < 0.001). Cluster-adjusted Poisson regression confirmed 21%-22% reductions in
      both (P < 0.001). Extended follow-up for 3 successive quarters demonstrated a
      sustained reduction of bacteremia rates for patients in intervention facilities,
      at 0.50/1,000 CVC-days (41% reduction; P < 0.001). Hospitalizations due to sepsis
      during 1-year extended follow-up were 0.19/1,000 CVC-days (0.069/CVC-year) versus
      0.26/1,000 CVC-days (0.095/CVC-year) in controls (~27% difference; P < 0.05).
      LIMITATIONS: Inability to capture results from blood cultures sent to external
      laboratories, underestimation of sepsis-specific hospitalizations, and potential
      crossover adoption of the intervention protocol in control facilities.
      CONCLUSIONS: Adoption of the new catheter care procedure (consistent with Centers
      for Disease Control and Prevention recommendations) resulted in a 20% lower rate
      of BSIs and intravenous antibiotic starts, which were sustained over time and
      associated with a lower rate of hospitalizations due to sepsis.

PMID- 24295614
TI  - A thermodynamic study of the third PDZ domain of MAGUK neuronal protein PSD-95
      reveals a complex three-state folding behavior.
AB  - The relevance of the C-terminal alpha helix of the PDZ3 domain of PSD95 in its
      unfolding process has been explored by achieving the thermodynamic
      characterization of a construct where the sequence of the nine residues
      corresponding to such motif has been deleted. Calorimetric traces at neutral pH
      require the application of a three-state model displaying three different
      equilibrium processes in which the intermediate state self-associates upon
      heating, being stable and populated in a wide temperature range. Temperature
      scans followed by circular dichroism, Fourier transform infrared spectroscopy and
      dynamic light scattering support the presence of such oligomeric-partially folded
      species. This study reveals that the deletion of the alpha3-helix sequence
      results in a more complex description of the domain unfolding. 

PMID- 24295615
TI  - The perceived benefits of belonging to an extra curricular group within a pre
      registration nursing course.
AB  - This study describes a qualitative research design that focuses on nursing
      students who were aligned to different extra-curricular groups (a student
      representative committee, a Nurses' Day Committee and a magazine editorial team)
      within the School of Health. The study explores the nursing students' experiences
      and perceptions of belonging to an extra-curricular group within a pre
      registration nursing course. Data were collected using focus groups. The findings
      of this study suggest that students who are members of extra-curricular groups
      perceive group membership to have many positive benefits. The findings were
      grouped into three main themes namely: employability, retention and personal
      gain. The findings suggest that students are clearly aware of their career
      development and expressed how group membership meant they were able to develop
      skills around employability. Students highlighted that they gained support and
      built lasting relationships through the groups which supported and reassured them
      which it was felt enabled them to progress successfully through the course. These
      themes reinforce the value of having established groups within a pre-registration
      curriculum.

PMID- 24295616
TI  - An introduction to the clinical phenomenology of Tourette syndrome.
AB  - Tourette syndrome (TS) is the primary tic disorder that reaches most commonly
      medical attention and monitoring, with an estimated prevalence close to 1%
      between 5 and 18 years of age. Motor and phonic tics are the core features of TS.
      In addition to their well-characterized phenomenology, tics display a peculiar
      variability over time, which is strongly influenced by a variety of contextual
      factors. The sensory phenomena of TS are increasingly recognized as another
      crucial symptom of TS and consist of premonitory urges and somatic
      hypersensitivity. A relevant proportion of patients with TS display complex, tic
      like, repetitive behaviors that include echophenomena, coprophenomena, and
      nonobscene socially inappropriate behaviors (NOSIBs). The burden of behavioral
      comorbidities is very important in determining the degree of disability of TS
      patients. Only a small minority of TS patients presents exclusively with a tic
      disorder. Obsessive-compulsive symptoms and related disorder (OCD) are common in
      TS, and the clinical distinction between compulsions and complex tics may be
      difficult in some cases. Probably, the presence of comorbid attention deficit
      hyperactivity disorder (ADHD) is the main determinant of cognitive dysfunction in
      TS patients and influences heavily also the risk of developing disruptive
      behaviors. Affective disorders, impulse control disorders, autism spectrum
      disorders, and personality disorders complete the wide psychopathological
      spectrum of this condition, but have been less investigated than OCD and ADHD.
      The complexity of the Tourette spectrum has been confirmed by cluster and factor
      analytical approaches, and is likely to inform the study of the genetic basis of
      this disorder, as well as future reappraisal of its nosography, with the
      development of novel clinical subtypes. 

PMID- 24295617
TI  - Functional neuroanatomy of tics.
AB  - The therapeutic success of haloperidol in the treatment of Tourette syndrome (TS)
      put an end to the discussion about a "hysteric" or "neurotic" origin of TS. The
      cortico-striato-thalamo-cortical circuit has been identified as an underlying
      neurobiological correlate of TS. In this review we explore the main findings of
      structural alterations in TS including cortical areas, basal ganglia,
      hippocampus, amygdala, midbrain, and cerebellum. Based on the structural changes
      we examine the functional pattern described by the findings of fMRI and (15)O
      PET/(18)FDG PET investigations. From the neuroimaging findings a cortical origin
      of the generation of tics is indicated. Future research on the neuronal footprint
      of TS should be directed towards addressing the question of which patterns of
      connectivity distinguish individuals in whom tics disappear during early
      adulthood from those in whom the tics persist. The understanding of this
      pathomechanism could provide a key on how to influence dysconnectivity in TS, for
      example, by more specific pharmaceutical intervention or by individually adopted
      EEG and/or fMRI neurofeedback. 

PMID- 24295618
TI  - Functional imaging of dopaminergic neurotransmission in Tourette syndrome.
AB  - Tourette syndrome (TS) is a heritable neuropsychiatric disorder that presents in
      childhood with a constellation of motor and nonmotor symptoms. Many of the
      earliest efforts to elucidate the anatomic substrate of TS focused on the
      contribution of the basal ganglia to the disorder. Simultaneously, however, a
      substantial body of evidence has accrued to implicate dysfunction of regions
      outside the basal ganglia in the generation of tics. In particular, while
      activation studies have shown evidence for cortico-striato-thalamo-cortical
      circuit abnormalities in TS, several other functional imaging reports have
      suggested that a dysregulation of striatal dopamine both at the presynaptic and
      postsynaptic level may play a primary role in TS. In addition, new radiotracers
      allowing for the investigation of extrastriatal dopamine seem to support the
      involvement of cortical structures as well. 

PMID- 24295619
TI  - Nondopaminergic neurotransmission in the pathophysiology of Tourette syndrome.
AB  - A major pathophysiological role for the dopaminergic system in Tourette's
      syndrome (TS) has been presumed ever since the discovery that dopamine-receptor
      antagonists can alleviate tics. Especially recent molecular genetic studies,
      functional imaging studies, and some rare postmortem studies have given more and
      more hints that other neurotransmitter systems are involved as well. Dysfunction
      in the dopamine metabolism-in particular during early development-might lead to
      counter-regulations in the other systems or vice versa. This chapter will give an
      overview of the studies that prove the involvement of other neurotransmitter
      systems such as the major monoaminergic neurotransmitters norepinephrine,
      serotonin, and histamine; the most important excitatory neurotransmitter, the
      amino acid glutamate; the major inhibitory neurotransmitter y-aminobutyric acid,
      as well as acetylcholine, endocannabinoid, corticoid; and others. These studies
      will hopefully lead to fundamental advances in the psychopharmacological
      treatment of TS. While tic disorders have been previously treated mainly with
      dopamine antagonists, some authors already favor alpha-agonists. Clinical trials
      with glutamate agonists and antagonists and compounds influencing the
      histaminergic system are currently being conducted. Since the different
      neurotransmitter systems consist of several receptor subtypes which might mediate
      different effects on locomotor activity, patients with TS may respond
      differentially to selective agonists or antagonists. Effects of agonistic or
      antagonistic compounds on tic symptoms might also be dose dependent. Further
      studies will lead to a broader spectrum of psychopharmacological treatment
      options in TS. 

PMID- 24295620
TI  - Reinforcement learning and Tourette syndrome.
AB  - In this chapter, we report the first experimental explorations of reinforcement
      learning in Tourette syndrome, realized by our team in the last few years. This
      report will be preceded by an introduction aimed to provide the reader with the
      state of the art of the knowledge concerning the neural bases of reinforcement
      learning at the moment of these studies and the scientific rationale beyond them.
      In short, reinforcement learning is learning by trial and error to maximize
      rewards and minimize punishments. This decision-making and learning process
      implicates the dopaminergic system projecting to the frontal cortex-basal ganglia
      circuits. A large body of evidence suggests that the dysfunction of the same
      neural systems is implicated in the pathophysiology of Tourette syndrome. Our
      results show that Tourette condition, as well as the most common pharmacological
      treatments (dopamine antagonists), affects reinforcement learning performance in
      these patients. Specifically, the results suggest a deficit in negative
      reinforcement learning, possibly underpinned by a functional hyperdopaminergia,
      which could explain the persistence of tics, despite their evident inadaptive
      (negative) value. This idea, together with the implications of these results in
      Tourette therapy and the future perspectives, is discussed in Section 4 of this
      chapter. 

PMID- 24295622
TI  - Pharmacological animal models of tic disorders.
AB  - This review summarizes animal models of Tourette syndrome (TS) and associated tic
      disorders that have been developed through pharmacological manipulation. These
      models provide a useful platform to explore the pathophysiology and the
      therapeutic interventions available for these disorders. The current
      pharmacological models, primarily using rodents and nonhuman primates, are
      classified in this review into two major categories depending on the methodology
      used for administration, that is, systemic and focal (intracerebral) injection
      protocols. The systemic protocol primarily targets monoamines such as dopamine
      and serotonin, whereas the focal protocol mainly manipulates local transmission
      of gamma-aminobutyric acid (GABA). Each category is capable of inducing
      behavioral abnormalities that are characteristic of TS spectrum disorders,
      ranging from sensorimotor to cognitive and emotional symptoms to various degrees.
      Among a variety of pharmacological models, focal microinjection of GABA
      antagonists into the sensorimotor striatum has helped identify abnormal neural
      discharge in the global networks which underlie tourettism, including not only
      the cerebral cortex and basal ganglia but also the cerebellum, consistent with
      recent neuroimaging studies for TS subjects. This unique model also provides the
      opportunity to clarify the effect and mechanisms of therapeutic deep brain
      stimulation. Continuing efforts to incorporate cutting-edge knowledge into the
      existing models, as well as to combine different model platforms, will allow
      further refinement of animal models, thereby leading to a greater understanding
      of TS and associated tic disorders. 

PMID- 24295623
TI  - Animal models recapitulating the multifactorial origin of Tourette syndrome.
AB  - Tourette Syndrome (TS) is a neurological disorder characterized by motor and
      phonic tics affecting approximately 1% of the pediatric population. Behavioral
      comorbidities often include obsessive-compulsive behavior and impaired attention.
      The neurobiological substrates associated with TS generally entail abnormalities
      in neurotransmitter circuitry regulating basal ganglia activity. The
      neurotransmitters most often associated with TS are dopamine, serotonin, and
      GABA. TS origin roots in genetic predisposing factors, and environmental
      variables favoring tic onset and exacerbation. Among the latter, repeated
      infections with group A beta-hemolytic Streptococcus and psychosocial stressors
      encountered during development have been proposed to constitute likely
      susceptibility factors. In this chapter, we describe how this
      clinical/epidemiological knowledge has been translated into animal models of TS.
      Specifically, we review several studies attempting to reproduce TS-like symptoms
      (tics and behavioral stereotypies) and comorbidities (impaired attention,
      increased locomotion, and perseverative responding) in laboratory rodents.
      Additionally, we discuss studies in which the genetic and environmental
      predisposing factors have been modeled in experimental subjects. Ultimately, we
      propose a unifying perspective recapitulating dependent and independent variables
      in the preclinical study of TS and discuss its potential theoretical and
      heuristic implications. 

PMID- 24295621
TI  - Genetic susceptibility and neurotransmitters in Tourette syndrome.
AB  - Family studies have consistently shown that Tourette syndrome (TS) is a familial
      disorder and twin studies have clearly indicated a genetic contribution in the
      etiology of TS. Whereas early segregation studies of TS suggested a single-gene
      autosomal dominant disorder, later studies have pointed to more complex models
      including additive and multifactorial inheritance and likely interaction with
      genetic factors. While the exact cellular and molecular base of TS is as yet
      elusive, neuroanatomical and neurophysiological studies have pointed to the
      involvement of cortico-striato-thalamocortical circuits and abnormalities in
      dopamine, glutamate, gamma-aminobutyric acid, and serotonin neurotransmitter
      systems, with the most consistent evidence being available for involvement of
      dopamine-related abnormalities, that is, a reduction in tonic extracellular
      dopamine levels along with hyperresponsive spike-dependent dopamine release,
      following stimulation. Genetic and gene expression findings are very much
      supportive of involvement of these neurotransmitter systems. Moreover,
      intriguingly, genetic work on a two-generation pedigree has opened new research
      pointing to a role for histamine, a so far rather neglected neurotransmitter,
      with the potential of the development of new treatment options. Future studies
      should be aimed at directly linking neurotransmitter-related genetic and gene
      expression findings to imaging studies (imaging genetics), which enables a better
      understanding of the pathways and mechanisms through which the dynamic interplay
      of genes, brain, and environment shapes the TS phenotype. 

PMID- 24295624
TI  - Neuroendocrine aspects of Tourette syndrome.
AB  - There is sparse evidence suggesting the participation of neuroendocrine
      mechanisms, mainly involving sex and stress steroid hormones, to the
      pathophysiology of neurodevelopmental disorders such as Tourette syndrome (TS)
      and obsessive-compulsive disorder (OCD). Patients with TS exhibit a sex-specific
      variability in gender distribution (male/female ratio=3-4/1) and in its natural
      history, with a severity peak in the period around puberty. The administration of
      exogenous androgens may worsen tics in males with TS, whereas drugs counteracting
      the action of testosterone might show some antitic efficacy. This suggests a
      higher susceptibility of patients with TS to androgen steroids. There are
      insufficient data on the regulation of the hypothalamic-pituitary-gonadal (HPG)
      axis in TS. However, preliminary evidence suggests that a subgroup of women with
      TS might be more sensitive to the premenstrual trough of estrogen levels.
      Patients with TS exhibit differences in a number of behavioral, cognitive, and
      anatomical traits that appear to be sex related. There is a body of evidence
      supporting, albeit indirectly, the hypothesis of an increased exposure to
      androgenic steroids during the very early phases of neural development. Animal
      models in rodents suggest a complex role of gonadal hormones upon the modulation
      of anxiety-related and stereotyped behaviors during adult life. Patients with TS
      exhibit an enhanced reactivity of the hypothalamic-pituitary-adrenal axis to
      external stressors, despite a preserved diurnal cortisol rhythm and a normal
      restoration of the baseline activity of the axis following the acute stress
      response. Preliminary evidence suggests the possible implication of oxytocin (OT)
      in disorders related to the TS spectrum, especially non-tic-related OCD. The
      injection of OT in the amygdala of rodents was shown to be able to induce
      hypergrooming, suggesting the possible involvement of this neuropeptide in the
      pathophysiology of complex, stereotyped behaviors. In contrast, there is
      anecdotal clinical evidence that tics improve following periods of affectionate
      touch and sexual intercourse. 

PMID- 24295625
TI  - Clinical pharmacology of dopamine-modulating agents in Tourette's syndrome.
AB  - Forty years of research and clinical practice have proved dopamine (DA) receptor
      antagonists to be effective agents in the treatment of Tourette's syndrome (TS),
      allowing a significant tic reduction of about 70%. Their main effect seems to be
      mediated by the blockade of the striatal DA-D2 receptors. Various typical and
      atypical agents are available and there is still discord between experts about
      which of them should be considered as first choice. In addition, there are
      suggestions to use DA receptor agonists such as pergolide or non-DA-modulating
      agents. The present chapter is focusing on the clinical pharmacology of DA
      modulating agents in the treatment of TS. The introduction outlines their
      clinical relevance and touches on the hypotheses of the role of DA in the
      pathophysiology of TS. Subsequently, general information about the mechanisms of
      action and adverse effects are provided. The central part of the chapter forms a
      systematic review of all DA-modulating agents used in the treatment of TS,
      including an overview of studies on their effectiveness, and a critical
      discussion of their specific adverse effects. The present chapter closes with a
      summary of the body of evidence and a description of the resulting
      recommendations for the pharmacological treatment of TS. 

PMID- 24295626
TI  - Clinical pharmacology of nondopaminergic drugs in Tourette syndrome.
AB  - Treatment of tics and Gilles de la Tourette syndrome (GTS) by nondopaminergic
      drugs was initiated more than three decades ago. These approaches were driven by
      the wish to circumvent antipsychotic-related side effects (metabolic
      disturbances, parkinsonian syndromes, tardive dyskinesia) or to use these
      treatments as a valuable add-on therapy in patients at least partially refractory
      to antipsychotics. In this review, we will therefore discuss the potential value
      of treating tics with alpha2 receptor agonists, nicotine, tetrabenazine, GABA
      agonists, botulinum toxin, cannabinoids, and immune modulators (plasmapheresis,
      intravenous immunoglobulins, antibiotic prophylaxis). Future directions for
      clinical trials based on our expanding understanding of the pathophysiology of
      GTS with regard to cholinergic, glutamatergic, and histaminergic
      neurotransmission will also be briefly outlined. 

PMID- 24295627
TI  - Antiepileptic drugs and Tourette syndrome.
AB  - Tourette syndrome is a neurodevelopmental disorder characterized by the chronic
      presence of multiple motor tics and at least one vocal/phonic tic for the
      duration of 1 year. The clinical picture of patients with Tourette syndrome is
      often complicated by tic-related behavioral problems and associated
      psychopathology. The pathophysiology of Tourette syndrome is not thoroughly
      understood, however converging evidence from neuroimaging studies suggests
      abnormalities within the frontostriatal pathways which are mediated by several
      neurotransmitters. The pharmacological management of the tic symptoms focuses on
      the dopaminergic and noradrenergic pathways and aims to improve the health
      related quality of life of patients. The most common medications are neuroleptics
      and atypical antipsychotics, which have a strong D2 blocking action. Also,
      preliminary studies have documented the efficacy of antiepileptic drugs in
      controlling tics. Thus far, two anticonvulsants (topiramate and levetiracetam)
      have been tested with a randomized, double-blind, placebo-controlled procedure in
      the treatment of tics. A study has reported an improvement in the control of tics
      with topiramate. This pharmacological agent was also reported to be well
      tolerated by the patients. However, the most frequent observed topiramate side
      effects (such as somnolence, cognitive problems, and weight loss) could not have
      manifested because of the short trial duration. Levetiracetam has shown
      conflicting results. A study found significant improvements in the control of
      tics, also associated with improvement in school performance. These results,
      however, were not replicated in other studies. Further investigations are
      therefore needed to assess the real efficacy of antiepileptic drugs in the
      treatment of tics. 

PMID- 24295628
TI  - Clinical pharmacology of comorbid obsessive-compulsive disorder in Tourette
      syndrome.
AB  - Treatment of Tourette Syndrome (TS) and its comorbidities is symptomatic and
      directed to improve the patient's social functioning and quality of life, to
      reduce the impairment from comorbid disorders, and to control tics severity.
      Often the pharmacological treatment combined with the multidisciplinary treatment
      is intended for comorbid disorders rather than for the tics themselves. Obsessive
      compulsive disorder (OCD) is one of the most common comorbid conditions. Even so,
      to our knowledge no clinical trials have specifically evaluated the treatment of
      OC symptoms in TS patients. After a brief introduction to the treatment of pure
      OCD, in this chapter we will inspect data and information mostly drawn from the
      small number of clinical trials on efficacy of antiobsessional drugs that have
      also included patients with tics and compared their clinical effects in OCD
      subjects with and without tics. SRI or SSRI treatment will be presented, together
      with alternative strategies and novel therapeutic approaches for poor or no
      response. Data on safety and tolerability will be reviewed. 

PMID- 24295629
TI  - Clinical pharmacology of comorbid attention deficit hyperactivity disorder in
      Tourette syndrome.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most common comorbid
      condition in people with Tourette syndrome (TS), reported in 60-80% of TS
      clinical samples. The comorbidity between TS and ADHD appears to have a complex
      pathogenesis and genetic factors can be implicated. Even if the etiological
      relationship between TS and ADHD is unclear, it is clear that individuals with
      both TS and ADHD are at a much greater risk for a variety of poor outcomes. It
      has been largely reported that the presence of comorbid symptoms seems to have a
      more significant influence on the patient's quality of life than the presence of
      tics alone, and therefore it can be associated with a major need for
      pharmacological interventions. Nonpharmacological interventions, including
      psychotherapy, should be tried in patients with TS and comorbid ADHD before
      considering pharmacological treatment of ADHD symptoms. Available evidence
      suggests that the alpha 2-agonists should be the first-line treatment, followed
      by immediate release or sustained release psychostimulants as second choice, and
      atomoxetine as third-line treatment. Monitoring of emergence or worsening of tics
      is particularly recommended during a treatment course of psychostimulants. 

PMID- 24295630
TI  - Emerging treatment strategies in Tourette syndrome: what's in the pipeline?
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple
      motor/phonic tics and a wide spectrum of behavioral problems (e.g., complex tic
      like symptoms, attention deficit hyperactivity disorder, and obsessive-compulsive
      disorder). TS can be a challenging condition even for the specialists, because of
      the complexity of the clinical picture and the potential adverse effects of the
      most commonly prescribed medications. Expert opinions and consensus guidelines on
      the assessment and treatment of tic disorders have recently been published in
      Europe and Canada. All pharmacological treatment options are mere symptomatic
      treatments that alleviate, but do not cure, the tics. We still lack evidence of
      their effects on the natural long-term course and on the prognosis of TS and how
      these treatments may influence the natural course of brain development. The most
      commonly prescribed drugs are dopamine antagonists, such as typical (e.g.,
      haloperidol, pimozide) and atypical neuroleptics (e.g., risperidone,
      aripiprazole), and alpha-2-adrenoreceptor agonists (e.g., clonidine). However,
      several studies have investigated the efficacy and tolerability of alternative
      pharmacological agents that may be efficacious, including the newest atypical
      antipsychotic agents (e.g., paliperidone, sertindole), tetrabenazine, drugs that
      modulate acetylcholine (e.g., nicotine) and GABA (e.g., baclofen, levetiracetam),
      tetrahydrocannabinol, botulinum toxin injections, anticonvulsant drugs (e.g.,
      topiramate, carbamazepine), naloxone, lithium, norepinephrine, steroid 5alpha
      reductase, and other neuroactive agents (buspirone, metoclopramide,
      phytostigmine, and spiradoline mesylate). As regards nonpharmacological
      interventions, some of the more recent treatments that have been studied include
      electroconvulsive therapy and repetitive transcranial magnetic stimulation. This
      review focuses primarily on the efficacy and safety of these emerging treatment
      strategies in TS.

PMID- 24295631
TI  - Tics and other stereotyped movements as side effects of pharmacological
      treatment.
AB  - Tics and other stereotyped abnormal movements can be seen as adverse effects of
      some pharmacologic drugs. Among these drugs, antipsychotics may provoke tardive
      syndromes after a chronic exposure, primarily in the case of typical
      antipsychotics. These syndromes include tardive tics, tardive dyskinesia, or
      tardive akathisia, which present with tics or stereotyped movements as a clinical
      phenomenon. Psychostimulants (mainly methylphenidate) have traditionally been
      associated with the appearance of tics due to the increased dopamine activity
      caused by stimulants. Nevertheless, in recent years, several studies have
      concluded not only that methylphenidate does not exacerbate or reactivate tics
      but also that tics can improve with its use in patients with associated attention
      deficit and hyperactivity disorder and tic disorder. Antiepileptic drugs,
      although infrequently, can also induce tics, with carbamazepine and lamotrigine
      described as tic inducers. Other antiepileptics, including levetiracetam and
      topiramate, have been proposed as a potential treatment for tic disorders due to
      a positive effect on tics, especially in those with associated epileptic
      disorder. Clinical and therapeutic approaches to tics and stereotyped movements
      after exposure to antipsychotics, stimulants, and antiepileptic drugs will be
      reviewed in this chapter. 

PMID- 24295632
TI  - Preface: the metamorphoses of Gilles de la Tourette syndrome.

PMID- 24295633
TI  - Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior
      and binding of NMDA receptors in pre-pubertal rats.
AB  - In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX)
      on behavioral paradigms related to olfaction such as exploratory behavior,
      locomotor activity in a novel environment and social interaction. We also studied
      the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of
      glutamate receptors during development. The behavioral effects of nOBX (postnatal
      day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar
      rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain
      regions associated with the olfactory circuitry. A significant increase in the
      novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the
      locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested
      post-pubertally failed to habituate to the novel situation as quickly as the sham
      and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in
      nOBX rats compared with sham-operated and normal controls, while normal
      exploratory behavior was observed between groups in adulthood. In contrast,
      social interaction was increased in post-pubertal animals that underwent nOBX.
      Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre
      pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the
      piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex
      and outer layer of the cingulate cortex. At post-pubertal age, no significant
      differences in [(125)I]MK-801 binding were observed between groups at any of the
      brain regions analyzed. These results suggest that nOBX produces pre-pubertal
      behavioral disturbances and NMDA receptor changes that are transitory with
      recovery of olfaction early in adulthood. 

PMID- 24295634
TI  - AMPK activation regulates neuronal structure in developing hippocampal neurons.
AB  - AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions
      as a cellular and whole organism energy sensor to regulate ATP-consuming
      (anabolic) and ATP-generating (catabolic) pathways. The heterotrimeric AMPK
      complex consists of a catalytic alpha-subunit, regulatory beta-subunit, and an
      AMP/ATP-binding gamma-subunit. Several alternate isoforms exist for each subunit
      (alpha1, alpha2, beta1, beta2, gamma1, gamma2 and gamma3). However, little is
      known of the expression pattern or function of the individual catalytic complexes
      in regulating neuronal structure. In this study, we examined the role of AMPK
      subunits in differentiating hippocampal neurons. We found that during
      development, the expression of AMPK subunits increase and that activation of AMPK
      by energetic stress inhibits neuronal development at multiple stages, not only
      during axon outgrowth, but also during dendrite growth and arborization. The
      presence of a single functional AMPK catalytic complex was sufficient to mediate
      these inhibitory effects of energetic stress. Activation of AMPK mediates these
      effects by suppressing both the mTOR and Akt signaling pathways. These findings
      demonstrate that the energy-sensing AMPK pathway regulates neuronal structure in
      distinct regions of developing neurons at multiple stages of development. 

PMID- 24295635
TI  - Self vs. other: neural correlates underlying agent identification based on
      unimodal auditory information as revealed by electrotomography (sLORETA).
AB  - Recent neuroscientific studies have identified activity changes in an extensive
      cerebral network consisting of medial prefrontal cortex, precuneus, temporo
      parietal junction, and temporal pole during the perception and identification of
      self- and other-generated stimuli. Because this network is supposed to be engaged
      in tasks which require agent identification, it has been labeled the evaluation
      network (e-network). The present study used self- versus other-generated movement
      sounds (long jumps) and electroencephalography (EEG) in order to unravel the
      neural dynamics of agent identification for complex auditory information.
      Participants (N=14) performed an auditory self-other identification task with
      EEG. Data was then subjected to a subsequent standardized low-resolution brain
      electromagnetic tomography (sLORETA) analysis (source localization analysis).
      Differences between conditions were assessed using t-statistics (corrected for
      multiple testing) on the normalized and log-transformed current density values of
      the sLORETA images. Three-dimensional sLORETA source localization analysis
      revealed cortical activations in brain regions mostly associated with the e
      network, especially in the medial prefrontal cortex (bilaterally in the alpha-1
      band and right-lateralized in the gamma-band) and the temporo-parietal junction
      (right hemisphere in the alpha-1-band). Taken together, the findings are partly
      consistent with previous functional neuroimaging studies investigating unimodal
      visual or multimodal agent identification tasks (cf. e-network) and extent them
      to the auditory domain. Cortical activations in brain regions of the e-network
      seem to have functional relevance, especially the significantly higher cortical
      activation in the right medial prefrontal cortex. 

PMID- 24295636
TI  - Intraperitoneal vascular endothelial growth factor burden in peritoneal surface
      malignancies treated with curative intent: the first step before intraperitoneal
      anti-vascular endothelial growth factor treatment?
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) is one of the most
      important angiogenic factors in solid tumours and plays an important role in
      ascites development in peritoneal surface malignancies (PSM). The main goal of
      this study was to determine the evolution and factors influencing intraperitoneal
      (IP) VEGF burden during cytoreductive surgery (CRS) with curative intent.
      PATIENTS AND METHODS: Ninety-seven consecutive patients with PSM were treated
      with CRS at a single centre with curative intent. Patient data were collected
      prospectively between February 2012 and October 2012. An enzyme-linked
      immunosorbent assay technique was used to assess VEGF levels in intravenous (IV)
      systemic blood samples before incision and after abdominal closure, and in IP
      samples during abdominal cavity exploration, after completion of CRS, after
      hyperthermic IP chemotherapy, and at 1 and 24h after abdominal closure. RESULTS:
      The IP VEGF burden increased significantly after CRS, and then decreased
      progressively (p<0.005). In multivariate analysis, neoadjuvant IV bevacizumab
      significantly decreased the preoperative IP VEGF burden, tumour load according to
      Peritoneal Cancer Index value increased significantly the preoperative IP VEGF
      burden and a low preoperative IP VEGF burden was associated with significantly
      increased postoperative complications. Neoadjuvant IV bevacizumab is the only
      factor that influences the preoperative IV VEGF concentration. CONCLUSION: For
      patients with PSM who were treated with curative intent, the IP VEGF burden
      increased after CRS, and was reduced prior to surgery by the administration of
      neoadjuvant IV bevacizumab.

PMID- 24295638
TI  - International expert opinion on patient-tailored management of soft tissue
      sarcomas.
AB  - BACKGROUND: Soft tissue sarcomas (STS) are a heterogeneous group of cancers
      comprising over 50 histological subtypes. Current treatment strategies for
      sarcomas are increasingly adapted to histological and molecular subtype, and
      several patient- and tumour-related factors influence treatment decision.
      METHODS: Seven oncologists specialising in the management of STS, from Europe,
      the United States of America and Japan, met to develop a practical model to
      identify parameters guiding treatment decision-making in advanced STS. Literature
      searches were carried out to identify key published evidence, in particular phase
      II and III randomised trials, to validate the model, and extensive clinical
      experience was used as expert evidence. A document was developed to provide a
      logical approach to advanced STS management and was analysed critically by a
      second group of STS specialists. RESULTS: Broad consensus was reached during this
      exercise and the following parameters were identified as key factors influencing
      treatment decision: chemosensitivity of histological subtype, natural history of
      the diagnosis, tumour burden, tumour site, locally advanced primary and/or
      metastases, patient's general condition, relevant comorbidities, previous
      chemotherapy, treatment goal and patient acceptance. These parameters, judged
      useful for treatment selection, were based on published literature, the selection
      process within clinical trials and expert opinion (some factors have not been
      formerly defined in published literature). CONCLUSION: A model describing factors
      affecting treatment decisions in sarcoma was established. The model requires
      validation and several of its parameters require standardisation.

PMID- 24295637
TI  - Functional single nucleotide polymorphisms of the RASSF3 gene and susceptibility
      to squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: RASSF3 suppresses tumour formation through uncertain mechanisms, but
      it is an important gene of p53-dependent apoptosis. RASSF3 depletion impairs DNA
      repair after DNA damage, leading to polyploidy. The authors hypothesised that
      potential functional single-nucleotide polymorphisms (SNPs) of RASSF3 are
      associated with risk of squamous cell carcinoma of the head and neck (SCCHN).
      METHODS: The authors used a functional SNP approach to evaluate the associations
      between common (minor allele frequency?0.05), putative functional variants in
      RASSF3 and risk of SCCHN. Four selected such functional SNPs (rs6581580 T>G,
      rs7313765 G>A, rs12311754 G>C and rs1147098 T>C) in RASSF3 were identified and
      genotyped in 1087 patients and 1090 cancer-free controls in a non-Hispanic white
      population. RESULTS: The authors found that two SNPs were significantly
      associated with SCCHN risk. Carriers of the variant rs6581580G and rs7313765A
      alleles were at a reduced SCCHN risk, compared with the corresponding common
      homozygotes [adjusted odds ratio (OR)=0.75 and 0.73 and 95% confidence interval
      (CI)=0.62-0.91 and 0.60-0.88, respectively, for dominant models; and Ptrend=0.012
      and 0.041, respectively, for additive models], particularly for non-oropharyngeal
      tumours (adjusted OR=0.68 and 0.60 and 95% CI=0.53-0.86 and 0.47-0.77,
      respectively, for dominant models). In the genotype-phenotype correlation
      analysis of peripheral blood mononuclear cells from 102 cancer-free controls, the
      rs6581580 GG genotype was associated with significantly increased expression
      levels of RASSF3 mRNA (P=0.038), compared with the TT genotype. Additional
      functional experiments further showed that variant G allele of rs6581580 had a
      significantly stronger binding affinity to the nuclear protein extracts than the
      T allele. CONCLUSION: Taken together, these findings indicate that the RASSF3
      promoter rs6581580 T>G SNP is potentially functional, modulating susceptibility
      to SCCHN among non-Hispanic whites. Larger replication studies are needed to
      confirm our findings.

PMID- 24295639
TI  - Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with
      symptomatic brain metastases: final results of an open-label pilot study.
AB  - BACKGROUND & AIM: Brain metastases are frequent in patients with metastatic
      melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor
      vemurafenib in patients with advanced melanoma with symptomatic brain metastases.
      METHODS: This open-label trial assessed vemurafenib (960mg twice a day) in
      patients with BRAF(V600) mutation-positive metastatic melanoma with non
      resectable, previously treated brain metastases. The primary end-point was
      safety. Secondary end-points included best overall response rate, and progression
      free and overall survival. RESULTS: Twenty-four patients received vemurafenib for
      a median treatment duration of 3.8 (0.1-11.3) months. The majority of
      discontinuations were due to disease progression (n=22). Twenty-three of 24
      patients reported at least one adverse event (AE). Grade 3 AEs were reported in
      four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included
      cutaneous squamous cell carcinoma in four patients. Median progression-free
      survival was 3.9 (95% CI, 3.0-5.5) months, and median survival was 5.3 (95% CI,
      3.9-6.6) months. An overall partial response (PR) at both intracranial and
      extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable
      patients, with stable disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19
      patients with measurable intracranial disease, seven (37%) achieved >30%
      intracranial tumour regression, and three (16%; 95% CI, 3.4-39.6%) achieved a
      confirmed PR. Other signs of improvement included reduced need for
      corticosteroids and enhanced performance status. CONCLUSIONS: Vemurafenib can be
      safely used in patients with advanced symptomatic melanoma that has metastasised
      to the brain and can result in meaningful tumour regression.

PMID- 24295640
TI  - Effects of Cagemate Gender and the Cagemate's access to ethanol on ethanol and
      water intake of the proximal male or the proximal female CD-1 mouse.
AB  - The effects of social stimulation on ethanol drinking in humans may depend on the
      gender of the drinker, the gender of the social stimulus, and the availability of
      ethanol provided to the social stimulus. The present study employed the Proximal
      Cagemate Drinking (PCD) Procedures to evaluate the effects of the gender of the
      social stimulus Cagemate mouse and the effects of providing ethanol to the
      Cagemate mouse on the drinking of ethanol and water by the male or female CD-1
      Drinker mouse. Twelve groups of subjects were arranged in a 3 * 2 * 2 factorial
      design with 3 levels of Cagemate Gender (Male vs. Female vs. None), 2 levels of
      Drinker Gender (Male vs. Female), and 2 levels of Cagemate Ethanol (Ethanol vs.
      No Ethanol). In the 8 groups assigned to social housing conditions, each Drinker
      mouse was housed with a Cagemate mouse on opposite sides of a clear plastic
      shoebox cage equipped with a clear plastic barrier that divided the cage
      lengthwise into 2 equal compartments. Six groups of Drinkers and 4 groups of
      Cagemates were provided with continuous access to 2 bottles (ethanol vs. water),
      while the 4 groups of Cagemates in the No Ethanol condition were provided with 2
      bottles containing water. Results revealed that providing the Cagemate with
      ethanol elevated ethanol intake and ethanol preference but reduced water intake
      in Drinkers in Other-Gender Pairings (Male Drinker-Female Cagemate or Female
      Drinker-Male Cagemate) relative to Drinkers in Same-Gender Pairings (Male Drinker
      Male Cagemate or Female Drinker-Female Cagemate). In contrast, when the Cagemate
      was not provided with access to ethanol, the opposite effects were observed.
      These novel PCD procedures reveal that the gender of the Cagemate and the
      Cagemate's access to ethanol influenced ethanol drinking in proximal-housed CD-1
      Drinker mice. 

PMID- 24295641
TI  - Restoring trust in the pharmaceutical sector on the basis of the SSRI case.
AB  - The lack of public trust in the pharmaceutical sector (i.e. industry, authorities
      and doctors) could compromise the future of drug development and the regulatory
      system. Public trust integrates two important components, namely the
      vulnerability of the truster and the competence of the trustee. Because trust
      appears to have eroded as a result of drug safety controversies, this paper
      analyzes the role of public trust during the selective serotonin reuptake
      inhibitor (SSRI) and suicidality controversy focusing on the aforementioned trust
      components. Because the competence component of trust is argued to be paramount
      in determining and maintaining public trust, the SSRI case shows that this
      component is a part of public trust where these institutions can build on, and
      might therefore be better used to substantiate and reinforce, public trust.
      Efforts to build trust should rely on the ethical, professional (competence) and
      societal commitment of institutions and individuals to protect the vulnerability
      of the public during controversies. Because shared values can create trust or
      increase its levels within a specific environment, industry, authorities and
      physicians ought to develop novel and cooperative strategies to highlight their
      shared values and motivations. Rules, regulations and settlements are
      indispensable tools but undue regulation is costly and can backfire on the rather
      sensitive trust relationships in the pharmaceutical sector. 

PMID- 24295642
TI  - Drug enterohepatic circulation and disposition: constituents of systems
      pharmacokinetics.
AB  - Drug disposition information constitutes a part of systems pharmacokinetics, and
      becomes imperative when a drug shows significant effects at its disproportionally
      low blood concentration. The situation could result from outweighing the parent
      drug in tissues over in blood and/or from its active metabolites. Fractions of
      certain drugs absorbed from the intestine to the systemic circulation via the
      portal vein can return to the intestine via the bile duct and the sphincter of
      Oddi - a complementary nonrenal elimination route termed the enterohepatic
      circulation (EHC). Here, we critically evaluate the existing methods, techniques
      and animal models used for determining drug distribution, elimination and EHC,
      and collectively portray characteristics of 43 drugs that undergo EHC. EHC could
      represent an unexplored way to excrete unwanted substrates out of the body. The
      interdisciplinary analysis galvanizes our efforts to overcome technical gaps in
      drug discovery and development. 

PMID- 24295643
TI  - Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy.
AB  - Ganglioside GD2 is highly expressed on neuroectoderm-derived tumors and sarcomas,
      including neuroblastoma, retinoblastoma, melanoma, small cell lung cancer, brain
      tumors, osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma in children and
      adolescents, as well as liposarcoma, fibrosarcoma, leiomyosarcoma and other soft
      tissue sarcomas in adults. Since GD2 expression in normal tissues is restricted
      to the brain, which is inaccessible to circulating antibodies, and in selected
      peripheral nerves and melanocytes, it was deemed a suitable target for systemic
      tumor immunotherapy. Anti-GD2 antibodies have been actively tested in clinical
      trials for neuroblastoma for over the past two decades, with proven safety and
      efficacy. The main limitations have been acute pain toxicity associated with GD2
      expression on peripheral nerve fibers and the inability of antibodies to treat
      bulky tumor. Several strategies have been developed to reduce pain toxicity,
      including bypassing complement activation, using blocking antibodies, or
      targeting of O-acetyl-GD2 derivative that is not expressed on peripheral nerves.
      To enhance anti-tumor efficacy, anti-GD2 monoclonal antibodies and fragments have
      been engineered into immunocytokines, immunotoxins, antibody drug conjugates,
      radiolabeled antibodies, targeted nanoparticles, T-cell engaging bispecific
      antibodies, and chimeric antigen receptors. The challenges of these approaches
      will be reviewed to build a perspective for next generation anti-GD2 therapeutics
      in cancer therapy. 

PMID- 24295644
TI  - Intestinal volvulus and its increased incidence in patients with Cornelia de
      Lange syndrome.

PMID- 24295645
TI  - Tuberculosis infection following anti-TNF therapy in inflammatory bowel disease,
      despite negative screening.
AB  - We present two patients with inflammatory bowel disease who, despite negative
      tuberculosis screening, developed a de novo tuberculosis infection after the
      start of anti tumor necrosis factor alpha treatment. We discuss current screening
      methods and their limitations, the approach after positive screening and the
      timing to resume anti-TNFalpha treatment after TB infection. We shortly mention
      the immune reconstitution inflammatory syndrome (IRIS), described in a few cases
      after the stop of anti-TNFalpha while treating the tuberculosis infection. We
      conclude with some remaining questions concerning tuberculosis in IBD patients.

PMID- 24295647
TI  - Pneumatosis intestinalis and perforation in Crohn's disease: worrisome or not?

PMID- 24295646
TI  - Delphi consensus statement: Quality Indicators for Inflammatory Bowel Disease
      Comprehensive Care Units.
AB  - BACKGROUND AND AIMS: While it is commonly accepted that Inflammatory bowel
      disease (IBD) Comprehensive Care Units (ICCUs) facilitate the delivery of quality
      care to Crohn's disease and ulcerative colitis patients, it remains unclear how
      an ICCU should be defined or evaluated. The aim of the present study was to
      develop a comprehensive set of Quality Indicators (QIs) of structure, process,
      and outcomes for defining and evaluating an ICCU. METHODS: A Delphi consensus
      based approach with a standardized three-step process was used to identify a core
      set of QIs. The process included an exhaustive search using complementary
      approaches to identify potential QIs, and two Delphi voting rounds to select the
      QIs defining the core requirements for an ICCU. RESULTS: The consensus selected a
      core set of 56 QIs (12 structure, 20 process and 24 outcome). Structure and
      process QIs highlighted the need for multidisciplinary management and continuity
      of care. The minimal IBD team should include an IBD nurse, gastroenterologists,
      radiologists, surgeons, endoscopists and stoma management specialists. ICCUs
      should be able to provide both outpatient and inpatient care and admission should
      not break the continuity of care. Outcome QIs focused on the adequate prophylaxis
      of disease complication and drug adverse events, the need to monitor
      appropriateness of treatment and the need to reinforce patient autonomy by
      providing adequate information and facilitating the patients' participation in
      their own care. CONCLUSIONS: The present Delphi consensus identified a set of
      core QIs that may be useful for evaluating and certifying ICCUs.

PMID- 24295648
TI  - Unique endoscopic findings of colitis-associated colorectal cancer in a patient
      with ulcerative colitis and Lynch syndrome.

PMID- 24295649
TI  - Robinin modulates TLR/NF-kappaB signaling pathway in oxidized LDL induced human
      peripheral blood mononuclear cells.
AB  - This study was designed to investigate whether robinin administration modulates
      toll-like receptor (TLR) and nuclear factor-kappa B (NF-kappaB) signaling pathway
      in oxidized LDL induced human peripheral blood mononuclear cells (hPBMCs). The
      hPBMCs were isolated from healthy human volunteers and the cells were cultured in
      collagen coated plates at 37 degrees C with 5% CO2 and RPMI as culture medium and
      were grouped as follows: Group I - control, group II - OxLDL treated and group
      III - OxLDL+robinin (6MUg/ml). We measured mRNA expression of TLR2 and TLR4 by
      reverse-transcriptase polymerase chain reaction (RT-PCR) and NF-kappaB
      transcription factor assay (ELISA), and western blotting studies were done for
      knowing expression of monocyte chemotactic protein-1 (MCP 1), tumor necrosis
      factor-alpha (TNF-alpha) interleukin-6 (IL-6) and vascular cell adhesion molecule
      1 (VCAM-1). The result indicates that OxLDL that induces hPBMCs showed an
      upregulated expression of TLR2, TLR4, NF-kappaB, pro-inflammatory cytokines and
      VCAM-1. Robinin inhibited the ox-LDL induced TLR2 and TLR4 expression at mRNA
      level and inhibited the translocation of NF-kappaB p65 by modulating the TLR-NF
      kappaB signaling pathway thereby inhibiting cytokine production and down
      regulated inflammatory enzymes like cyclooxygenase (COX), lipoxygenase (LOX),
      nitric oxide synthase (NOS) and prostaglandin E2 (PGE2), thus having protective
      effect against the ox-LDL induced inflammation stress in hPBMCs by inhibiting
      TLR4-NF-kappaB signaling pathway. 

PMID- 24295650
TI  - Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta
      induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model.
AB  - Cartilage degradation is the most predominant pathological change during
      osteoarthritis (OA). Furthermore, accumulating evidence suggests that an excess
      of matrix metalloproteinase-13 (MMP-13) plays a critical role in the breakdown of
      cartilage. Here, the effects of Icariin on the expression of MMP-13 in IL-1beta
      induced SW 1353 chondrosarcoma cells were investigated. In addition, the in vivo
      effects of Icariin on an experimental rat model of OA induced by anterior
      cruciate ligament transection (ACLT) was examined. SW1353 chondrosarcoma cells
      were pretreated with or without Icariin and MAPK and Wnt/beta-catenin signaling
      pathway inhibitors, then were stimulated with IL-1beta. In rats, experimental OA
      was induced by ACLT. These rats then received intra-articular injections of
      vehicle, signaling pathway inhibitors, and/or Icariin. Expression of MMP-13,
      phosphorylated p38, phosphorylated JNK, and beta-catenin were verified by western
      blotting. In addition, levels of MMP-13 mRNA were detected using quantitative
      real-time PCR. In histological analyses, treatment with Icariin reduced the
      number of cartilage lesions present. In addition, treatment with Icariin was
      associated with lower levels of phosphorylated p38, phosphorylated JNK, and beta
      catenin in both IL-1beta-induced SW1353 chondrosarcoma cells and in the rat OA
      model. Furthermore, the suppressive effect of Icariin on MMP-13 was greater than
      that exhibited by other signaling pathway inhibitors. Overall, these data suggest
      that Icariin has therapeutic potential for the treatment of OA. 

PMID- 24295651
TI  - Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS
      induced inflammatory responses via suppressing NF-kappaB and MAPK pathways in RAW
      264.7 cells.
AB  - This study investigates the anti-inflammatory effects of a stilbene compound,
      desoxyrhapontigenin, which was isolated from Rheum undulatum. To determine the
      anti-inflammatory effects of this compound, lipopolysaccharide (LPS)-induced RAW
      264.7 macrophages were treated with different concentrations of six stilbene
      derivatives. The results indicated that compared with other stilbene compounds,
      desoxyrhapontigenin (at 10, 30 and 50MUM concentrations) significantly inhibited
      nitric oxide (NO) production, nuclear factor kappa B (NF-kappaB) activation, the
      protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase (iNOS) expression. Therefore, the anti-inflammatory mechanism of
      desoxyrhapontigenin was investigated in detail. The results of this investigation
      demonstrated that desoxyrhapontigenin suppressed not only LPS-stimulated pro
      inflammatory cytokine secretions, including the secretions of tumor necrosis
      factor alpha (TNF-alpha) and interleukin-6 (IL-6), but also PGE2 release. As
      assayed by electrophoretic mobility shift assays (EMSAs), desoxyrhapontigenin
      also produced the dose-dependent inhibition of the LPS-induced activation of NF
      kappaB and AP-1. Moreover, desoxyrhapontigenin inhibited the protein expression
      of myeloid differentiation primary response gene 88 (MyD88), IkappaB kinase (IKK)
      phosphorylation and the degradation of IkappaBalpha. Activations of p-JNK1 and p
      Akt were also significantly inhibited, and phosphorylation of p38 and ERK was
      down-regulated. A further study revealed that desoxyrhapontigenin (5 and 25mg/kg,
      i.p.) reduced paw swelling in carrageenan-induced acute inflammation model in
      vivo. On the whole, these results indicate that desoxyrhapontigenin showed anti
      inflammatory properties by the inhibition of iNOS and COX-2 expression via the
      down-regulation of the MAPK signaling pathways and the inhibition of NF-kappaB
      and Akt activation. 

PMID- 24295652
TI  - Pharmacokinetics of anti-IL17A and anti-IL22 peptide-antibody bispecific genetic
      fusions in mice.
AB  - The peptide-antibody (Ab) genetic fusion is a promising technology for targeting
      multiple antigens in a single Ab-like molecule. We have recently described
      generation and in vitro characterization of several such genetic fusions, using
      an interleukin (IL)-17A binding peptide and an anti-IL-22 Ab as a model system.
      In this study we assessed pharmacokinetic profiles of these model genetic fusions
      in mice. Specifically an IL-17A binding peptide was fused to either the heavy
      chain or both the heavy and the light chains of an anti-IL22 human IgG1 (referred
      to Compounds 1 or 2, respectively). Swiss Webster mice were given a single 10
      mg/kg IV dose of Compound 1 or Compound 2 and serum concentrations were measured
      by a fused molecule immunoassay, in which IL-17A was used as a capture and anti
      human IgG was used as a detector. In addition, serum samples were assayed using a
      total human IgG immunoassay. PK parameters were calculated by non-compartmental
      modeling. The two genetic fusions had similar PK profiles, with total body
      clearance of ~0.9-1.0 mL/h/kg, volume of distribution at steady-state of ~63-65
      mL/kg, and elimination half-life of ~40 h. Our study provides the first
      characterization of the PK properties of peptide-Ab genetic fusions and suggests
      that although these genetic fusions appear to be eliminated faster than a typical
      Ab, the PK profile may be suitable for preclinical and clinical testing.

PMID- 24295654
TI  - Trachea: anatomy and physiology.
AB  - The windpipe (trachea) is a tube of 12 cm length connecting the larynx to the
      principal bronchi that lead to the lungs. The main functions of the trachea
      comprise air flow into the lungs, mucociliary clearance, and humidification and
      warming of air. Mucociliary clearance is achieved by kinocilia and goblet cells
      in the mucosa, and by tracheal glands. The trachea develops from the endodermal
      lining of the foregut in interaction with the visceral mesoderm. During adult
      life, different types of stem cells reside in the mucosal epithelium and
      glandular ducts. Recently, cholinergic chemosensory cells have been described in
      the trachea. 

PMID- 24295653
TI  - Therapeutic vaccination against relevant high virulence clinical isolates of
      Mycobacterium tuberculosis.
AB  - The purpose of this study was to attempt to develop therapeutic or post-exposure
      vaccines that could slow progressive disease in guinea pigs infected by low dose
      aerosol with very high virulence Beijing isolates of Mycobacterium tuberculosis,
      currently classified as Category C biodefense pathogens by the NIH and CDC. After
      screening several candidates we focused on the use of three candidates; these
      were a pool of bacterial iron acquisition proteins, a pool of antigens recognized
      by T cells from chronically infected mice thought to represent proteins made by
      the bacillus in response to decreases in local oxygen tension, and a bacterial
      lipoprotein that is a potent TLR2 agonist. When delivered in a potent GLA-based
      adjuvant [targeting TLR4 and TLR9], in most cases we were unable to reduce the
      bacterial load in the lungs. However, the pathologic appearance of lungs from
      these animals showed that, while primary lesions were most unaffected and had
      become necrotic, the development of large, lung consolidating secondary lesions
      seemed to have been mostly prevented. In animals given both a priming vaccination
      and a boost the effects were prominent, and almost certainly contributed to
      significantly prolonged survival in these animals. In a biodefense situation,
      this prolonged survival would be potentially long enough to allow for the
      organism to be identified and a drug susceptibility profile determined. 

PMID- 24295655
TI  - Pathology of tracheal tumors.
AB  - Malignant involvement of the trachea predominantly results from direct spread of
      neighboring tumors to the tracheal wall. Primary tracheal malignancies show a low
      incidence of approximately 0.1 in every 100,000 persons per year, squamous cell
      carcinomas and adenoid cystic carcinomas accounting for about two-thirds of adult
      primary tracheal tumors. The etiology of squamous cell carcinoma and its
      premalignant lesions is strongly associated with tobacco smoking. Patients with
      tracheal malignancies show an unfavorable prognosis, with reported 5- and 10-year
      survival rates of 5% to 15% and 6% to 7%, respectively, for all types of tracheal
      carcinoma. 

PMID- 24295656
TI  - Anesthesia and gas exchange in tracheal surgery.
AB  - Tracheobronchial surgery constitutes a challenge to the anesthetist because it
      involves the anatomic structures dedicated to bulk gas transport. Common
      approaches to airway management and gas exchange for extrathoracic and
      intrathoracic airway surgery are reviewed, with due regard to less common methods
      thought crucial for specific procedures. Tracheal surgery, beyond sharing the
      airways, requires sharing with the surgeon ideas on preoperative assessment, on
      the impact on gas exchange of induction across compromised airways, and of
      emergence from anesthesia with airways altered by surgical repair. Mutual
      understanding is essential to prevent, rapidly identify, and correct imminent
      loss of airway viability. 

PMID- 24295657
TI  - Endoscopic treatment of tracheal stenosis.
AB  - For all cases of tracheal obstructions surgery should be considered first.
      Interventional endoscopic procedures can provide immediate relief. Intraluminally
      growing tumors can be resected with laser, argon-plasma coagulation, an
      electrosurgical knife or cryo-probe. Photodynamic therapy of smaller tracheal
      tumors can be curative. Narrowing from intramural tumor growth or wall
      destruction requires internal splinting with an airway stent. Scar strictures can
      be dilated with balloons but the biotrauma may stimulate new scarring. In benign
      strictures and malacias, tracheal stents should only be placed if all other
      methods are exhausted. Complications including stent migration, mucostasis,
      halitosis and granulation tissue development must be considered. Most important
      for a good outcome is a multidisciplinary approach. 

PMID- 24295658
TI  - Repair of tracheobronchial injuries.
AB  - Tracheobronchial injuries (TBIs) are caused by blunt, penetrating injury or by
      iatrogenic damage. Most injuries are life threatening and need early and skillful
      airway management. Bronchoscopy remains the gold standard of diagnosis.
      Penetrating TBI always needs blunt trauma, and iatrogenic TBI sometimes needs
      surgical exploration and reconstruction, which is performed after sparing
      debridement with primary repair and wound closure. Prognosis mainly depends on
      associated injuries and comorbidities in terms of tracheal membrane laceration. 

PMID- 24295659
TI  - Tracheomalacia.
AB  - Tracheomalacia is excessive collapsibility of the trachea, typically during
      expiration. Congenital forms are associated with severe symptoms. Milder forms
      often present after the neonatal period. Adult malacia is mostly associated with
      chronic obstructive pulmonary disease. Functional bronchoscopy is still not
      standardized. Dynamic airway CT is a promising tool for noninvasive diagnosis.
      Bronchoscopy and stent insertion lead to significant improvement, but with a high
      complication rate. Surgical lateropexia, tracheal resection, and surgical
      external stabilization are options. Tracheoplasty seems to be the best choice for
      selected cases of adult malacia. The most commonly performed surgery in children
      is aortopexy. 

PMID- 24295660
TI  - Benign stenosis of the trachea.
AB  - Benign stenosis of trachea results mainly from tracheotomy, ventilation, or
      trauma. The combination of a defect of the mucosa or the tracheal wall and
      infection produce secondary scar tissue healing with shrinkage of the tracheal
      lumen or instability of the tracheal wall. Standard of treatment consists of
      resection of the pathologic segment of the trachea with end-to-end anastomosis.
      In case of involvement of the larynx, partial resections of the anterior cricoid
      cartilage or division of the larynx with tracheolaryngeal silicone stents are
      used. Short-term and long-term results are satisfying considering some technical
      recommendations. 

PMID- 24295661
TI  - Laryngotracheal resection and reconstruction.
AB  - Patients with tracheal stenosis can experience life-threatening dyspnea. When the
      stenosis is close to the larynx, management can be challenging. Non-definitive
      palliative measures should be kept to a minimum as they can make definitive
      management more complicated. Specialized techniques of resection and
      reconstruction of high tracheal lesions are available and lead to excellent
      relief of symptoms. A detailed knowledge of the anatomy, the extent of the
      stenosis, and careful attention to surgical technique is crucial. Excellent
      results can be achieved in experienced centers that are able to anticipate and
      thus avoid complications that can be difficult to manage. 

PMID- 24295662
TI  - Treatment approaches to primary tracheal cancer.
AB  - A patient identified with tracheal cancer benefits most from evaluation by an
      experienced center and an extensive effort to assess the possibility of a
      complete surgical resection as the most efficient treatment option for cure.
      Localized, nonoperable disease may still be controlled by combined modality using
      chemotherapy and concurrent radiation. 

PMID- 24295663
TI  - Carinal resection and sleeve pneumonectomy.
AB  - Carinal resection and sleeve pneumonectomy are rare procedures and challenging
      issues in thoracic surgery. In spite of the knowledge of the technique, the
      incidence of postoperative complications is higher compared with standard
      resections. Adequate patient selection, improved anesthetic management and
      surgical technique, and better postoperative management might reduce the rate of
      postoperative morbidity and mortality. 

PMID- 24295664
TI  - Extended tracheal resections.
AB  - There is no universally valid definition of the extent of tracheal resections
      that would be considered "extended." Underlying disease, necessary length of
      resection, anatomic localization, and chosen surgical approach account for a
      manifold interdependency. Existing data suggest a "cutoff margin" of 4 cm or
      more, referring to the likelihood of complications and necessity of additional
      mobilization maneuvers. This overview outlines worldwide experiences and the
      surgical variety of possibilities, as well as their execution and appropriate
      use.

PMID- 24295665
TI  - Airway transplantation.
AB  - No definitive solution has been discovered for replacing long segments or the
      entire trachea in humans. Most of this challenge stems from the specific function
      and mechanics that are almost impossible to replicate except in the setting of an
      allotransplantation, which requires lifelong immunosuppressive medication.
      Recently, tissue engineering provided significant evidence concerning the next
      promising therapeutic alternative for tracheal replacement. Underlying mechanism
      and pathways of cell-surface interactions, cell migration, and differentiation
      are essential to understand the complexity of tracheal tissue regeneration.
      Tracheal replacement remains challenging but initial steps toward an ideal
      therapeutic concept have been made. 

PMID- 24295666
TI  - Management of tracheal surgery complications.
AB  - Complications in tracheal surgery are not uncommon but generally do not influence
      the final result. Most patients benefit from tracheal resections and mortality is
      low. Risk factors for complications are reoperations, preoperative tracheostomy,
      and lengthy resections. Precise information about the extent of the diseased
      tracheal part as well as thorough planning of the operative procedure, meticulous
      dissection, and knowledge of release maneuvers by an experienced thoracic surgeon
      will diminish the risk of adverse effects. Granuloma formation is the most common
      event observed postoperatively, whereas dehiscence and restenosis or the
      potentially fatal bleeding from a tracheo-innominate artery fistula occurs less
      frequently. 

PMID- 24295667
TI  - Treatment of malignant tracheoesophageal fistula.
AB  - This article addresses the treatment of malignant enterorespiratory fistulas,
      especially malignant tracheoesophageal fistula (mTEF). mTEF typically occurs
      after radiochemotherapy for advanced esophageal cancer. Life expectancy is
      measured in months after successful treatment, and in days to weeks with a
      persistent fistula. To stop repeated episodes of aspiration and septic pneumonia,
      single or double stenting of the esophagus and trachea with self-expandable
      coated stents is the established palliative treatment. The indications,
      techniques, and pitfalls of esophageal and tracheal stenting are described.
      Surgical interventions are justified only in very select cases, so this article
      focuses on interventional rather than surgical treatment. 

PMID- 24295668
TI  - Tracheal surgery. Preface.

PMID- 24295669
TI  - Effects of L- and iso-ascorbic acid on meat protein hydrolyzing activity of four
      commercial plant and three microbial protease preparations.
AB  - The present study investigated the effects of both l- and iso-ascorbic acid (AA)
      on the activity of four plant proteases (papain, bromelain, actinidin and
      zingibain) and three microbial proteases (Bacterial Protease G, Fungal 31,000 and
      Fungal 60,000) preparations using fluorescent-labelled casein, meat myofibrillar
      and connective tissue extracts to explore their effects on meat structure
      components upon treatment with individual proteases. While l-AA in the range 0.8
      3.2mM inhibited the activity of papain, bromelain and zingibain, iso-AA acted as
      an inhibitor of papain but as an activator of zingibain and had no significant
      effect on bromelain. Both AA isoforms acted as an activator of the actinidin
      protease and the concentration of AA isoforms appeared to affect the level of
      activation of the protease. The effect of the two AA isoforms on collagen and
      myofibrillar protein hydrolyzing activity varied depending on the concentration
      of the two AA isoforms. The results indicate the ability to up and down regulate
      the activity of the investigated proteases by using an appropriate concentration
      of the AA isoform. 

PMID- 24295670
TI  - Dynamics of sterols and fatty acids during UV-B treatment of oyster mushroom.
AB  - Fruiting bodies of the oyster mushroom Pleurotus ostreatus were illuminated with
      UV-B with a light intensity maximum at 310-320 nm and 11.5 W/m2 for 60 min at 20 
      degrees C. Changes of the sterol and fatty acid spectrum were quantified. The
      onset of ergocalciferol (vitamin D2) formation was immediate in fruiting bodies
      illuminated from the lamella side, in sliced fruiting bodies, and in the stipes.
      Saturation concentrations above 100 MUg/g of dry matter were reached after 1h. At
      the same time, the concentrations of the photo-isomers lumisterol2, tachysterol2
      and previtamin D2 increased in this order. 22-Dihydroergocalciferol (vitamin D4),
      showed the same course of increase and reached a maximum concentration of around
      20 MUg/g dry matter. With the exception of linoleic acid in cut fruiting bodies,
      fatty acid concentrations remained almost constant. One serving of UV-B
      pretreated sliced oyster mushroom covered the weekly demand of vitamin D of an
      adult.

PMID- 24295671
TI  - Simultaneous determination of phenolic compounds in Cynthiana grape (Vitis
      aestivalis) by high performance liquid chromatography-electrospray ionisation
      mass spectrometry.
AB  - Phenolic acids, flavanols, flavonols and stilbenes (PAFFS) were isolated from
      whole grapes, juice, or pomace and purified using enzymatic hydrolysis. Only
      anthocyanin mono-glucosides and a few of the oligomers from Cynthiana grape
      (Vitis aestivalis) were analysed. Flavonoid-anthocyanin mono-glucosides (FA) were
      isolated using methanol/0.1% hydrochloric acid extraction. In addition, crude
      extractions of phenolic compounds from Cynthiana grape using 50% methanol, 70%
      methanol, 50% acetone, 0.01% pectinase, or petroleum ether were also evaluated.
      Reverse phase high performance liquid chromatography (RP-HPLC) with photodiode
      array (PDA) detector was used to identify phenolic compounds. A method was
      developed for simultaneous separation, identification and quantification of both
      PAFFS and FA. Quantification was performed by the internal standard method using
      a five points regression graph of the UV-visible absorption data collected at the
      wavelength of maximum absorbance for each analyte. From whole grape samples nine
      phenolic compounds were tentatively identified and quantified. The individual
      phenolic compounds content varied from 3 to 875 mg kg-1 dry weight. For juice,
      twelve phenolic compounds were identified and quantified. The content varied from
      0.07 to 910 mg kg-1 dry weight. For pomace, a total of fifteen phenolic compounds
      were tentatively identified and quantified. The content varied from 2 mg kg-1 to
      198 mg kg-1 dry matter. Results from HPLC analysis of the samples showed that
      gallic acid and (+)-catechin hydrate were the major phenolic compounds in both
      whole grapes and pomace. Cyanidin and petunidin 3-O-glucoside were the major
      anthocyanin glucosides in the juice.

PMID- 24295672
TI  - Potential modulation on P-glycoprotein and CYP3A by soymilk and miso: in vivo and
      ex-vivo studies.
AB  - P-glycoprotein (P-gp) and CYP3A4 both play very important roles in drug
      bioavailability, resistance and interactions. Our in vitro studies indicated that
      P-gp function was activated by many isoflavones. This study investigated the in
      vivo effects of soymilk and miso, isoflavone-rich soy foods, on P-gp and CYP3A by
      tracing the pharmacokinetics of cyclosporine (CSP), a probe drug of P-gp. Rats
      were orally administered CSP with and without soymilk or miso. A specific
      monoclonal fluorescence polarisation immunoassay was used to determine the blood
      concentration of CSP. The results showed that soymilk and miso significantly
      decreased the C(max) of CSP by 64.5% and 78.3%, and reduced the AUC(0-540) by
      64.9% and 78.3%, respectively. Mechanism studies revealed that the activities of
      P-gp and CYP3A4 were induced by soymilk and miso. In conclusion, ingestion of
      soymilk and miso significantly activated the functions of P-gp and CYP3A.

PMID- 24295673
TI  - Lipolysis and lipid oxidation during processing of Chinese traditional smoke
      cured bacon.
AB  - Lipolysis and lipid oxidation as well as the relationship between them during
      processing of Chinese traditional smoke-cured bacon were studied by evaluating
      the changes in physicochemical parameters, lipase and lipoxygenase (LOX)
      activities, lipid content, fatty acid composition, peroxide value (POV), and
      thiobarbituric acid reactive substances (TBARS). Besides phospholipids,
      triacylglycerols (TAG) were an important source of free fatty acids in bacon,
      resulting in an increase in free fatty acid content in the mid-late stage of
      processing, whilst phospholipids hydrolysed intensely in the early stage.
      Preferential lipolysis was observed for polyunsaturated fatty acids in
      phospholipids and for linoleic and palmitic acids in TAG. The lipolysis of TAG
      and phospholipids was independent and catalysed by acid lipase and phospholipase,
      respectively. ANOVA-partial least squares regression (APLSR) analysis showed that
      POV and TBARS were poorly related to LOX and closely associated with phospholipid
      degradation. Therefore, autoxidation may be the main cause of muscle lipid
      oxidation in smoke-cured bacon, which was promoted by phospholipid hydrolysis. 

PMID- 24295674
TI  - Spaghetti from durum wheat: effect of drying conditions on heat damage,
      ultrastructure and in vitro digestibility.
AB  - The effects of low (LT) or high (HT) temperature drying on ultrastructural,
      molecular and in vitro digestibility properties of cooked spaghetti were studied.
      Starch swelling and denaturation/aggregation of proteins occurring at diverse
      stages, LT or HT drying and cooking, resulted in different in vitro digestibility
      of spaghetti. For the first time, these differences were assessed in terms of the
      release of free AA and simple sugars. Indeed, at the end of in vitro digestion,
      the total amount of released maltotriose, maltose and glucose significantly
      differentiated digestates of LT and HT spaghetti (12.6 and 15.9 g 100g-1). In the
      same samples, diverse amounts (16.3 and 12.5 g 100g-1 protein) of free amino
      acids were found. Chemical artifacts occurring at protein level impaired release
      of lysine in cooked HT spaghetti after in vitro digestion. These results increase
      the knowledge on digestibility of LT and HT cooked spaghetti.

PMID- 24295675
TI  - Interactions of buttermilk with curcuminoids.
AB  - The ability of buttermilk to carry and stabilise a preparation of curcuminoids
      was examined. The quenching of intrinsic protein fluorescence confirmed that the
      curcuminoids interacted with proteins in buttermilk. The Stern-Volmer quenching
      constant was >= 9.4 * 103 M-1. The apparent binding constant of curcuminoids to
      whole buttermilk was >= 2.2 * 104 M-1. Centrifugation of buttermilk (5% total
      solids, TS)--curcuminoid mixtures demonstrated that curcuminoids were partitioned
      into the cream (18.0%w/w, 0.64% TS), milk serum (73.3%w/w, 2.86% TS) and the
      casein-rich precipitate (6.76% w/w, 1.87% TS) fractions in the ratio of
      1:3.7:3.5. The interaction of curcuminoids with components in the buttermilk
      improved its stability, as evidenced by the faster degradation of curcuminoids in
      phosphate buffer (pH=6.8) than in buttermilk. The ability of buttermilk to carry
      and stabilise curcuminoids has the potential to enable the delivery of these
      components into functional foods.

PMID- 24295676
TI  - Comparison of four kinds of extraction techniques and kinetics of microwave
      assisted extraction of vanillin from Vanilla planifolia Andrews.
AB  - Vanillin yield, microscopic structure, antioxidant activity and overall odour of
      vanilla extracts obtained by different treatments were investigated. MAE showed
      the strongest extraction power, shortest time and highest antioxidant activity.
      Maceration gave higher vanillin yields than UAE and PAE, similar antioxidant
      activity with UAE, but longer times than UAE and PAE. Overall odour intensity of
      different vanilla extracts obtained by UAE, PAE and MAE were similar, while
      higher than maceration extracts. Then, powered vanilla bean with a sample/solvent
      ratio of 4 g/100 mL was selected as the optimum condition for MAE. Next, compared
      with other three equations, two-site kinetic equation with lowest RMSD and
      highest R2(adj) was shown to be more suitable in describing the kinetics of
      vanillin extraction. By fitting the parameters C(eq), k1, k2, and f, a kinetics
      model was constructed to describe vanillin extraction in terms of irradiation
      power, ethanol concentration, and extraction time.

PMID- 24295677
TI  - Amazonian palm Oenocarpus bataua ("patawa"): chemical and biological antioxidant
      activity--phytochemical composition.
AB  - In French Guiana, "diversity" within the Palm family is obvious since more than
      75 species have been identified. Oenocarpus bataua Mart., called "patawa" is well
      known for its culinary uses whereas literature on its phytochemical composition
      and biological properties remains poor. This work deals with determining the
      antioxidant activity of this palm fruit and its polyphenol composition; Euterpe
      oleracea (acai) used as a reference. It turned out that patawa had a stronger
      antioxidant activity than acai in TEAC and FRAP tests. A similar activity was
      observed by DPPH assay whereas in ORAC and KRL tests, that acai showed an
      antioxidant activity respectively 2.6 and 1.5 fold higher than patawa.
      Polyphenolic composition, determined by UPLC/MS(n), would imply the presence of
      anthocyanins, condensed tannins, stilbenes and phenolic acids, well known for
      their biological activities. These results present patawa fruit as a new
      amazonian resource for cosmetics, food and pharmaceuticals purposes. 

PMID- 24295678
TI  - Determination of residual enrofloxacin in food samples by a sensitive method of
      chemiluminescence enzyme immunoassay.
AB  - A chemiluminescence enzyme immunoassay (CLEIA) based on the HRP-luminol-H2O2
      chemiluminescence system for highly sensitive detection of enrofloxacin (ENR) was
      proposed in this study. Key factors that affect the precision and accuracy for
      the determination of ENR residues were optimised. Under the optimal conditions,
      the proposed method showed an excellent performance. The linearity range for
      method developed for determination of ENR was 0.35-1.0 ng/mL with a correlation
      coefficient greater than 0.994. The limit of detection was 0.03 ng/mL and the
      relative standard deviations (RSDs) were less than 9.4% and 13.0% for intra-day
      and inter-day assays. The proposed method was satisfactorily applied to determine
      ENR in milk, eggs, and honey samples at three spiked levels (0.4, 0.7, and 1.0
      ng/mL) and the recoveries ranged from 92.4% to 104.2% for milk, 93.8% to 103.2%
      for eggs and 94.1% to 105.0% for honey, respectively. Compared the results of
      CLEIA with those of ELISA and HPLC, the advantages of the CLEIA were further
      confirmed. Moreover, one 96-well microtiter plate coated with anti-ENR can be
      used to detect multiple samples at the same time, which indicated that the CLEIA
      using HRP-luminol-H2O2 system was a sensitive, high throughput and real-time
      method for ENR residues analysis.

PMID- 24295679
TI  - Optimization and characterization of purified polysaccharide from Musa sapientum
      L. as a pharmaceutical excipient.
AB  - Polysaccharides from Musa sapientum (MSP) were isolated and purified by gel
      filtration chromatography. Elemental analysis, scanning electron microscopy
      (SEM), X-ray diffraction crystallography (XRD), differential scanning calorimetry
      (DSC), Fourier-transform infrared spectroscopy (FT-IR) and NMR techniques were
      used to characterize the polysaccharide. Elemental analysis of the polysaccharide
      indicated that the contents of carbon, hydrogen and nitrogen to be 27.31, 5.07
      and 0.62 (w/w%) respectively. SEM analysis suggested that the polysaccharide had
      irregular particle size, mostly seen as aggregates, and fibrous in nature. The
      samples had peaks at approximately 25 degrees , 32 degrees , 40 degrees  and 43
      degrees  2theta degrees in the XRD pattern, which indicated both crystalline and
      amorphous structure. The major functional groups identified from FT-IR spectrum
      includes 1631.38 cm-1 (-COO-), 1377 cm-1 (-COO-) and 3193.93 cm-1 (-OH).
      Analytical data on MSP indicated that the major neutral sugars were alpha-D
      glucose, beta-D-glucose, rhamnose and D-glucuronic acid. The experimental work
      provides enough evidence to exploit this neutral biopolymer in food and
      pharmaceutical industry.

PMID- 24295680
TI  - Contribution of botanical origin and sugar composition of honeys on the
      crystallization phenomenon.
AB  - The present work provides information regarding the statistical relationships
      among the palynological characteristics, sugars (fructose, glucose, sucrose,
      melezitose and maltose), moisture content and sugar ratios (F+G, F/G and G/W) of
      136 different honey types (including bramble, chestnut, eucalyptus, heather,
      acacia, lime, rape, sunflower and honeydew). Results of the statistical analyses
      (multiple comparison Bonferroni test, Spearman rank correlations and principal
      components) revealed the valuable significance of the botanical origin on the
      sugar ratios (F+G, F/G and G/W). Brassica napus and Helianthus annuus pollen were
      the variables situated near F+G and G/W ratio, while Castanea sativa, Rubus and
      Eucalyptus pollen were located further away, as shown in the principal component
      analysis. The F/G ratio of sunflower, rape and lime honeys were lower than those
      found for the chestnut, eucalyptus, heather, acacia and honeydew honeys (>1.4). A
      lower value F/G ratio and lower water content were related with a faster
      crystallization in the honey. 

PMID- 24295681
TI  - Effects of gamma irradiation on chemical composition and antioxidant potential of
      processed samples of the wild mushroom Macrolepiota procera.
AB  - It was previously demonstrated that gamma irradiation was the processing
      technology with the highest capacity to maintain the chemical profile of fresh
      Macrolepiota procera wild mushroom, when compared to freeze-dried or oven-dried
      samples. Herein, it was aimed to evaluate gamma irradiation effects on processed
      samples. Chemical composition and antioxidant potential of irradiated (0.5 and 1
      kGy) fresh, frozen and dried samples were determined by chromatographic
      techniques and in vitro assays, respectively. M. procera irradiation attenuated
      the effects caused by oven-drying or freezing; combining freeze treatment with
      0.5 kGy dose preserved total tocopherols. Rather than a conservation methodology,
      gamma irradiation might act as a useful adjuvant to other conservation techniques
      (e.g., freezing or oven-drying).

PMID- 24295682
TI  - Lignin binding to pancreatic lipase and its influence on enzymatic activity.
AB  - In this paper, we find that the effect of lignin on pancreatic lipase (PL) is
      dependent on reaction medium and substrate used. Experimental results reveal that
      lignin can gradually bind to PL to form a PL-lignin complex, resulting in an
      increased activity of the enzyme. The binding process is spontaneous and the PL
      lignin complex formation is an endothermic reaction induced by hydrophobic and
      electrostatic interaction. There is a non-radiation energy transfer from PL to
      lignin during the binding process, and the binding of lignin to PL conforms to a
      secondary exponential decay function. Moreover, the alpha-helix content of the
      enzyme will be changed and the rigidity of its side chain will be enhanced due to
      the formation of lignin-PL complex. This study has not only provided the
      activation effect of lignin on PL, but also given an insight into the interaction
      between lignin and the enzyme, which would benefit the application of lignin in
      the pharmacy and food industry, as well as other fields. 

PMID- 24295683
TI  - Browning inhibition and quality preservation of button mushroom (Agaricus
      bisporus) by essential oils fumigation treatment.
AB  - The effect of essential oil fumigation treatment on browning and postharvest
      quality of button mushrooms (Agaricus bisporus) was evaluated upon 16 days cold
      storage. Button mushrooms were fumigated with essential oils, including clove,
      cinnamaldehyde, and thyme. Changes in the browning index (BI), weight loss,
      firmness, percentage of open caps, total phenolics, ascorbic acid, microbial
      activity and activities of polyphenol oxidase (PPO), phenylalanine ammonia lyase
      (PAL), and peroxidase (POD) were measured. The results indicated that all
      essential oils could inhibit the senescence of mushrooms, and the most effective
      compound was cinnamaldehyde. Fumigation treatment with 5 MUl l-1 cinnamaldehyde
      decreased BI, delayed cap opening, reduced microorganism counts, promoted the
      accumulation of phenolics and ascorbic acid. In addition, 5 MUl l-1
      cinnamaldehyde fumigation treatment inhibited the activities of PPO and POD, and
      increased PAL activity during the storage period. Thus, postharvest essential oil
      fumigation treatment has positive effects on improving the quality of button
      mushrooms.

PMID- 24295684
TI  - Probing the micellar solubilisation and inter-micellar exchange of polyphenols
      using the DPPH. free radical.
AB  - Encapsulation of polyphenols can be used for improving their stability and
      targeting. We present here a spectrophotometric method to probe the micellar
      solubilisation and inter-micellar exchange of polyphenols using the 2,2-diphenyl
      1-picrylhydrazyl (DPPH.) free radical as a visible probe. Our method relies on
      the partitioning of DPPH. into micelles, on the reduction of DPPH. by
      polyphenols, and on the change in absorbance of DPPH. when reduced/oxidised.
      Hence, an absorbance drop at 528 nm gives evidence of the co-localisation of
      polyphenols and DPPH. in micelles. Using catechin and sodium dodecyl sulfate
      (SDS) as model molecules, we have shown that the reduction stoichiometry
      increases up to the critical micelle concentration (CMC) of SDS, where it reaches
      a plateau: this is due to the solubilisation of catechin in pre-micellar
      aggregates and then in micelles. The initial rate of reduction increases with
      increasing SDS concentration up to the CMC and then decreases due to a dilution
      effect.

PMID- 24295685
TI  - Degradation of LIM domain-binding protein three during processing of Spanish dry
      cured ham.
AB  - Extensive proteolysis takes place during the processing of dry-cured ham due to
      the action of muscle peptidases. The aim of this work was to study the
      degradation of LIM domain binding protein 3 (LDB3), which is located at the Z
      lines of the sarcomere, at different times during the Spanish dry-cured ham
      processing (2, 3.5, 5, 6.5, and 9 months). A total of 107 peptides have been
      identified by mass spectrometry, most of them generated from the first region of
      the protein sequence (position 1-90) providing evidence for the complexity and
      variability of proteolytic reactions throughout the whole process of dry-curing.
      Methionine oxidation has been observed in several peptides by the end of the
      process. The potential of some of the identified peptides to be used as
      biomarkers of dry-cured ham processing has also been considered.

PMID- 24295686
TI  - Effect of different temperature-time combinations on lipid and protein oxidation
      of sous-vide cooked lamb loins.
AB  - Forty-five lamb loins were subjected to sous-vide cooking at different
      combinations of temperature (60, 70 and 80  degrees C) and time (6, 12 and 24 h)
      to assess the effect on the oxidative stability of lipids and proteins. Heating
      induced both lipid and protein oxidation in lamb loins. Higher cooking
      temperature-time combinations increased conjugated dienes and decreased
      thiobarbituric reactive substances (TBARS) values and hexanal. Total protein
      carbonyls increased throughout time at all cooking temperatures considered, while
      alpha-aminoadipic (AAS) and gamma-glutamic semialdehydes (GGS) increased when
      cooking at 60  degrees C but not at 80  degrees C. Links between the decrease in
      secondary compounds from lipid oxidation due to cooking at higher temperatures
      and for longer times with the increased levels of 3-methylbutanal and greater
      differences between total protein carbonyls and AAS plus GGS were hypothesised.

PMID- 24295687
TI  - Sediments in concentrated green tea during low-temperature storage.
AB  - The formation and the main chemical components of sediments, including reversible
      tea sediments (RTS) and irreversible tea sediments (IRS), in concentrated green
      tea during low-temperature storage were studied. RTS was mainly formed in the
      first 10 days, and IRS was mainly formed between 20 and 40 days of storage. The
      RTS were the primary sediment, contributing more than 90% of the total sediment.
      The RTS comprised of polyphenols, total sugar, caffeine, flavones and proteins,
      while the IRS mainly comprised of oxalates of Ca, Mg, Ga and Mn. The total
      mineral content in the IRS (17.1%) was much higher than that in the RTS (2.6%)
      after 80 days of storage. The Ca, Mg, Mn and Ga contents in IRS were over 1.0%
      (w/w) each. About 75% of the IRS was soluble in 0.1 M aqueous HCl, with the
      oxalate accounting for 68%. Minerals and oxalic acid were the crucial factors in
      the IRS formation.

PMID- 24295688
TI  - Phenylketonuria: protein content and amino acids profile of dishes for
      phenylketonuric patients. The relevance of phenylalanine.
AB  - Phenylketonuria is an inborn error of metabolism, involving, in most cases, a
      deficient activity of phenylalanine hydroxylase. Neonatal diagnosis and a prompt
      special diet (low phenylalanine and natural-protein restricted diets) are
      essential to the treatment. The lack of data concerning phenylalanine contents of
      processed foodstuffs is an additional limitation for an already very restrictive
      diet. Our goals were to quantify protein (Kjeldahl method) and amino acid (18)
      content (HPLC/fluorescence) in 16 dishes specifically conceived for
      phenylketonuric patients, and compare the most relevant results with those of
      several international food composition databases. As might be expected, all the
      meals contained low protein levels (0.67-3.15 g/100 g) with the highest ones
      occurring in boiled rice and potatoes. These foods also contained the highest
      amounts of phenylalanine (158.51 and 62.65 mg/100 g, respectively). In contrast
      to the other amino acids, it was possible to predict phenylalanine content based
      on protein alone. Slight deviations were observed when comparing results with the
      different food composition databases.

PMID- 24295689
TI  - Optimisation of the extraction of phenolic compounds from apples using response
      surface methodology.
AB  - The extraction of phenolic compounds from apples was optimised using response
      surface methodology (RSM). A Box-Behnken design was conducted to analyse the
      effects of solvent concentration (methanol or acetone), temperature and time on
      the extraction of total phenolic content, total flavonoids and antioxidant
      capacity (FRAP and DPPH). Analysis of the individual phenolics was performed by
      HPLC in optimal extraction conditions. The optimisation suggested that extraction
      with 84.5% methanol for 15 min, at 28  degrees C and extraction with 65% acetone
      for 20 min, at 10  degrees C were the best solutions for this combination of
      variables. RSM was shown to be an adequate approach for modelling the extraction
      of phenolic compounds from apples. Most of the experiments with acetone solutions
      extracted more bioactive compounds, and hence they had more antioxidant capacity,
      however, chlorogenic acid and phloridzin had higher yields (32.4% and 48.4%,
      respectively) in extraction with methanol.

PMID- 24295690
TI  - A review of ethyl carbamate and polycyclic aromatic hydrocarbon contamination
      risk in cachaca and other Brazilian sugarcane spirits.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) have been identified in Brazilian
      sugarcane spirits. Contamination sources are: sugarcane burn before harvest and
      petroleum derivatives. PAHs concentration in spirits produced from burned cane
      was about 2-3 times higher than those from unburned cane. Benzo(a)pyrene (BaP) is
      present at less than 1%, and therefore is not a representative marker of cachaca
      contamination by PAHs. Ethyl carbamate (EC) is produced during both fermentation
      and distillation. During distillation, cupric ions may catalyse the conversion of
      cyanide to EC. In discontinuous distillation, the use of the heart fraction for
      bottling cachaca considerably decreases its concentration. In the continuous
      process, in which there is no separation of distillate, it is highly recommended
      to couple cooling devices and reflux systems to the distillation column.
      Consumers are at a greater risk of EC exposure from cachaca than from any other
      spirit. 

PMID- 24295691
TI  - Changes in the physicochemical characteristics, including flavour components and
      Maillard reaction products, of non-centrifugal cane brown sugar during storage.
AB  - Changes in the quality attributes of non-centrifugal cane brown sugar represented
      by physicochemical characteristics as well as flavour components and Maillard
      reaction products (MRPs) were monitored every 3 months over 1 year of storage.
      Stored cane brown sugar became darker, and its moisture content and water
      activity (a(w)) increased during storage. Fructose and glucose levels decreased
      as non-enzymatic browning via the Maillard reaction occurred in the stored
      sample, and a similar trend was also discovered in aconitic and acetic acids.
      Stored cane brown sugar lost its acidic and sulfuric odours (58.70-39.35% and
      1.85-0.08%, respectively); subsequently, the nutty and roasted aroma increased
      from 26.52% to 38.59% due to the volatile MRPs. The browning rate of stored cane
      brown sugar was positively associated with the development of volatile MRPs
      (Pearson's coefficient = 0.860), whereas the amount of 3-deoxyglucosone, an
      intermediate product of the Maillard reaction, had a lower association with the
      brown colour due to its relatively slow degradation rate.

PMID- 24295692
TI  - Semduramicin in eggs--the incompatibility of feed and food maximum levels.
AB  - The cross-contamination of non-target feeds with coccidiostats may result in the
      occurrence of their residues in food of animal origin. To assure food safety,
      maximum levels (ML) of coccidiostats have been set for both feed and food.
      However, scientific data are not available on the transfer of some coccidiostats
      from feed into food. This experiment was therefore designed to verify, whether
      the administration of compliant semduramicin-contaminated feed could cause the
      occurrence of volatile residues of coccidiostats in eggs. The laying hens
      received feed containing 0.27 +/- 0.034 mg/kg of semduramicin (ML=0.25 mg/kg).
      Semduramicin residues were detected in whole eggs after two days of
      administration of semduramicin-containing diet. A plateau level was achieved
      (16.1 +/- 5.19 MUg/kg, mean +/- SD) with the concentrations significantly
      exceeding the maximum level of semduramicin in eggs (2 MUg/kg). The results of
      this experiment might be a signal for the revision of the ML value.

PMID- 24295693
TI  - Volatile oil from striped African pepper (Xylopia parviflora, Annonaceae)
      possesses notable chemopreventive, anti-inflammatory and antimicrobial potential.
AB  - Fruits of Xylopia parviflora, well known as striped African pepper, are sold in
      the Cameroonian markets as a flavouring ingredient to make traditional soups. The
      essential oil hydrodistilled from fruits was analysed for in vitro biological
      activities, namely cytotoxic, anti-inflammatory, antimicrobial and antioxidant,
      by MTT, nitric oxide inhibitory assay, agar disc diffusion method, and DPPH and
      ABTS assays. The essential oil composition, analysed by GC and GC-MS, was
      dominated by monoterpene hydrocarbons (50.0%) responsible for the pepper odour,
      such as beta-pinene (34.0%) and alpha-pinene (10.3%). The oil induced a strong
      inhibitory effect on tumour cells MDA-MB 231 and HCT116, with inhibition values
      close to those of cisplatin. A dose-dependent decrease in NO production was noted
      in RAW 264.7 macrophages treated with the oil, revealing a promising anti
      inflammatory potential. The essential oil showed a measurable antimicrobial
      activity against all the species tested, while the radical scavenging activity
      was low. 

PMID- 24295694
TI  - Flavonoid metabolites transport across a human BBB model.
AB  - This study aimed to evaluate the transmembrane transport of different flavonoids
      (flavan-3-ols, anthocyanins and flavonols) and some of their metabolites
      (methylated and conjugated with glucuronic acid) across hCMEC/D3 cells (a blood
      brain barrier (BBB) model). Further metabolism of the tested compounds was
      assayed and their transport modulated in an attempt to elucidate the mechanisms
      behind this process. The transport across hCMEC/D3 cells was monitored in
      basolateral media at 1, 3 and 18 h by HPLC-DAD/MS. All the flavonoids and their
      metabolites were transported across hCMEC/D3 cells in a time-dependent manner. In
      general, the metabolites showed higher transport efficiency than the native
      flavonoid. No further biotransformation of the metabolites was found as
      consequence of cellular metabolism. Anthocyanins and their metabolites crossed
      this BBB cell model in a lipophilicity-dependent way. Quercetin transport was
      influenced by phosphatase modulators, suggesting a
      phosphorylation/dephosphorylation regulation mechanism. Overall, this work
      suggests that flavonoids are capable of crossing the BBB and reaching the central
      nervous system.

PMID- 24295695
TI  - Influence of the matrix composition on the volatility and sensory perception of 4
      ethylphenol and 4-ethylguaiacol in model wine solutions.
AB  - This study was aimed at investigating the influence of ethanol, wine polyphenols
      and yeast extract on the volatility of 4-ethylphenols in red wines. The use of
      solid-phase microextraction with short extraction times for the study of the
      headspace composition, revealed a strong influence of ethanol and polyphenols on
      reducing the volatility of 4-ethylphenols in a model wine. At the same time, the
      influence of ethanol and polyphenols on the perception of the "Brett character"
      (stable, manure, horse sweat and phenolic notes) due to 4-ethylphenols was
      evaluated by sensory analysis. Polyphenols and ethanol were found to have a
      significant influence on the olfactory perception of the tainted wines. On the
      contrary, a direct influence of yeast extract on the volatility of 4-ethylphenols
      was not observed, although some results suggested that the effectiveness of
      polyphenols in reducing the volatility of 4-ethylphenols could be limited by the
      presence of yeast proteins. 

PMID- 24295696
TI  - A new method for preconcentration and determination of mercury in fish, shellfish
      and saliva by cold vapour atomic absorption spectrometry.
AB  - The development of a method using solid phase extraction for preconcentration and
      determination of mercury by cold vapour atomic absorption spectrometry is
      described. Hg (II) ions are sorbed on a minicolumn packed with Amberlite XAD-4
      sorbent functionalised with 2-(2'-benzothiazolylazo)-p-cresol (BTAC). Then, a
      reducing solution was used for desorption and the transport of the analyte for
      subsequent detection. The assay presented a limit of detection of 0.011 MUg L-1
      (0.011 MUg g-1, for solid samples), a limit of quantification of 0.038 MUg L-1
      (0.038 MUg g-1, for solid samples), a precision of 0.50% (1.000 MUg L-1 Hg
      solution) and an enrichment factor of 46. The proposed method was applied to the
      determination of mercury in human saliva (0.055-0.200 MUg L-1). The following
      seafood collected in Todos os Santos Bay, Brazil was also analysed: bass (0.169
      0.195 MUg g-1), mullet (0.043-0.361 MUg g-1), shrimp (0.075-0.374 MUg g-1) and
      mussel (0.206-0.397 MUg g-1).

PMID- 24295697
TI  - Effect of electron beam on chemical changes of nutrients in infant formula.
AB  - Infant milk formula has recently been implicated as a transmission vehicle for an
      emerging foodborne pathogen, Enterobacter sakazakii, resulting in high mortality
      rates. Electron beam (e-beam) efficiently and non-thermally inactivates foodborne
      pathogens, including E. sakazakii, in infant milk formula. However, the effects
      of e-beam on chemical changes of nutrients in infant formula have not been
      determined. Therefore, the objective of this study was to fulfill this gap.
      Dehydrated infant milk formula was processed with e-beam at 0 (control) to 25
      kGy. Amino acid, fatty acid, and mineral profiles (AAP, FAP, and MP,
      respectively), as well as protein degradation and lipid oxidation, were
      determined. There were no differences (P>0.05) in FAP, AAP, and MP. SDS-PAGE
      electrophoresis qualitatively detected three major protein bands in all samples
      up to 25 kGy. Densitometry analysis of SDS-PAGE gels confirmed no size
      degradation (P>0.05) as a function of increased e-beam dose. Totol-volatile-basic
      nitrogen (TVBN) excluded (P>0.05) protein degradation due to microbial activity.
      There was no increase (P>0.05) in lipid oxidation, as assessed with
      thiobarbituric-reactive-substances (TBARS), except in samples processed at 25
      kGy. Dehydrated formula has low water activity, which likely protected nutrients
      from e-beam-induced chemical changes. This study demonstrates that proteins,
      lipids, and minerals in infant milk formula are stable when processed with e-beam
      up to 25 kGy at low temperature and under anaerobic conditions.

PMID- 24295698
TI  - Simple electrochemical sensor for caffeine based on carbon and Nafion-modified
      carbon electrodes.
AB  - A simple, economic, highly sensitive and highly selective method for the
      detection of caffeine has been developed at bare and Nafion-modified glassy
      carbon electrodes (GCE). The electrochemical behaviour of caffeine was examined
      in electrolyte solutions of phosphate buffer saline, sodium perchlorate, and in
      choline chloride plus oxalic acid, using analytical determinations by fixed
      potential amperometry, phosphate buffer saline being the best. Modifications of
      the GCE surface with poly(3,4-ethylenedioxythiophene) (PEDOT), Nafion, and multi
      walled carbon nanotubes were tested in order to evaluate possible sensor
      performance enhancements, Nafion giving the most satisfactory results. The effect
      of interfering compounds usually found in samples containing caffeine was
      examined at GCE without and with Nafion coating, to exclude interferences, and
      the sensors were successfully applied to determine the caffeine content in
      commercial beverages and drugs. 

PMID- 24295699
TI  - Effects of preservation methods on amino acids and 5'-nucleotides of Agaricus
      bisporus mushrooms.
AB  - In this study, the proximate composition, free amino acids content and 5'
      nucleotides in frozen, canned and salted Agaricus bisporus (A. bisporus) were
      investigated. We found that the three kinds of A. bisporus products were good
      sources of protein, with amount varying in the ranges of 16.54-24.35g/100g (dry
      weight). Freezing, canning and salting process, followed by 6months of storage
      led to a significant reduction in free amino acids, especially tyrosine, alanine,
      glutamine and cysteine. There were medium levels of MSG-like amino acids in
      frozen A. bisporus and canned A. bisporus, and low levels of MSG-like amino acids
      in salted A. bisporus. The mount of flavor 5'-nucleotides in frozen A. bisporus
      was higher than that of canned and salted A. bisporus. The present study thus
      suggests that freezing is beneficial for the preservation of A. bisporus. 

PMID- 24295700
TI  - Glucosinolates redox activities: can they act as antioxidants?
AB  - Glucosinolates are a class of secondary plant metabolites particularly occurring
      in Cruciferae with potential health-promoting properties, as their hydrolysis
      products, isothiocyanates, possess chemopreventive and antioxidant activities. In
      the present study, we systematically studied the in vitro redox behaviour of 15
      glucosinolates, by using a range of analytical methods measuring different
      activities: (i) radical scavenging activity toward peroxyl and toward ABTS
      radical (chain-breaking activity); (ii) capacity in modulating the in vitro
      resistance of human low-density lipoprotein (LDL) catalysed by copper (chelating
      and chain-breaking activity). Data obtained from different assays were compared
      and analysed by principal component analysis (PCA). PCA allowed us to identify a
      big cluster of glucosinolates (10 out 15 tested) that do not possess any
      antioxidant capacity; while, the other five glucosinolates showed moderate and
      specific antioxidant capacity. Notably, sinalbin and gluconasturtiin were highly
      active in scavenging ABTS radical and in protecting LDL from copper-catalysed
      oxidation, respectively. The overall results of this study indicate that just few
      glucosinolates can act as antioxidants. 

PMID- 24295701
TI  - Residue and risk assessment of pyridaben in cabbage.
AB  - The dissipation and residue of pyridaben in cabbage under field conditions were
      investigated. A sensitive, simple, and fast method for determining pyridaben in
      cabbage was established by high-performance liquid chromatography tandem mass
      spectrometry. The average recoveries were in the range of 90.29-95.00% with
      relative standard deviations ranging from 1.72% to 6.39%. The field results
      showed that pyridaben dissipated rapidly in cabbage and had a half-life of 2.8
      3.5 d. During harvest, the terminal residues of pyridaben were 0.01-0.80 mg/kg.
      Given that no maximum residue limit (MRL) has been set for pyridaben in cabbage,
      risk assessment was evaluated by using the risk quotient (RQ). Results indicated
      that the RQ value was significantly lower than RQ = 1. Thus, the effect of
      pyridaben in cabbage at the recommended dosage was negligible to humans. This
      study could provide guidance for the safe and reasonable use of pyridaben as a
      broad-spectrum acaricide and serve as a reference for the establishment of an MRL
      in China.

PMID- 24295702
TI  - Heat-induced denaturation and aggregation of actomyosin and myosin from
      yellowcheek carp during setting.
AB  - Thermal inactivation kinetics of Ca2+-ATPase, changes in turbidity and
      rheological properties of actomyosin and myosin from yellowcheek carp during
      setting at different temperatures were investigated. Actomyosin and myosin
      setting at 40-45  degrees C exhibited greater extent and more rapid Ca2+-ATPase
      inactivation compared to at 25-30  degrees C. Formation of protein aggregates and
      three-dimensional network structures of actomyosin and myosin at 25-30  degrees C
      was far less than those at 40-45  degrees C. Thermal stability of actomyosin was
      higher than that of myosin as revealed by its higher activation energy for the
      inactivation of Ca2+-ATPase. Actomyosin and myosin also exhibited different
      dynamic rheological properties, especially when the setting temperatures were 40
      and 45  degrees C.

PMID- 24295703
TI  - First evidence of C- and O-glycosyl flavone in blood orange (Citrus sinensis (L.)
      Osbeck) juice and their influence on antioxidant properties.
AB  - RP-LC-DAD-ESI-MS-MS separation/identification protocol has been employed for the
      identification and characterisation of nine C- and O-glycosyl flavonoids in Moro
      (Citrus sinensis (L.) Osbeck) juice grown in Southern Italy. For the first time
      we reported the presence of five C-glycosyl flavones (lucenin-2, vicenin-2,
      stellarin-2, lucenin-2 4'-methyl ether and scoparin), a 3-hydroxy-3
      methylglutaryl glycosyl flavonol (3-hydroxy-3-methylglutaryl glycosyl quercetin)
      and a flavone O-glycosides (chrysoeriol 7-O-neoesperidoside). Moreover, the
      influence of the identified C- and O-glycosyl flavonoids on the total antioxidant
      activity of crude juice has been evaluated on the basis of its ability to
      scavenge DPPH*, OH* and ABTS*+ radicals and to reduce iron.

PMID- 24295704
TI  - Phytochemical extraction, characterisation and comparative distribution across
      four mango (Mangifera indica L.) fruit varieties.
AB  - In this study we determined the qualitative composition and distribution of
      phytochemicals in peel and flesh of fruits from four different varieties of mango
      using mass spectrometry profiling following fractionation of methanol extracts by
      preparative HPLC. Gallic acid substituted compounds, of diverse core structure,
      were characteristic of the phytochemicals extracted using this approach. Other
      principal compounds identified were from the quercetin family, the hydrolysable
      tannins and fatty acids and their derivatives. This work provides additional
      information regarding mango fruit phytochemical composition and its potential
      contribution to human health and nutrition. Compounds present in mango peel and
      flesh are likely subject to genetic control and this will be the subject of
      future studies. 

PMID- 24295705
TI  - Isolation and characterization of acid-soluble collagen from the scales of marine
      fishes from Japan and Vietnam.
AB  - Acid-soluble collagen (ASC) was successfully extracted from the scales of lizard
      fish (Saurida spp.) and horse mackerel (Trachurus japonicus) from Japan and
      Vietnam and grey mullet (Mugil cephalis), flying fish (Cypselurus melanurus) and
      yellowback seabream (Dentex tumifrons) from Japan. ASC yields were about 0.43
      1.5% (on a dry weight basis), depending on the species. The SDS-PAGE profile
      showed that the ASCs were type I collagens, and consisted of two different alpha
      chains, alpha1 and alpha2, as well as a beta component. ASC of horse mackerel
      from Vietnam contained a higher imino acid level than that from Japan. ASC
      denaturation temperature (Td) ranged from 26 to 29  degrees C, depending on fish
      species and imino acid content (p<0.01). Maximal solubility of individual
      collagens was observed at pHs 1-3. Collagen solubility decreased sharply at NaCl
      concentrations >0.4M, regardless of fish type.

PMID- 24295706
TI  - Attenuation of histopathological alterations of colon, liver and lung by dietary
      fibre of barley Rihane in azoxymethane-treated rats.
AB  - This study was carried out to determine the effect of dietary fibre (DF) of
      barley Rihane (BR) in the attenuation of colon, liver and lung histopathology
      alterations induced by azoxymethane (AOM) in rats. Rats were fed a control (C) or
      experimental diet containing 30% of BR. The intended rats for cancer treatment
      received two successive subcutaneous injections of azoxymethane (AOM) at 20mg/kg
      body weight. The colons were analyzed for crypt multiplicity after 12 weeks of
      treatment. A histological study of the colon, liver and lungs was determined. The
      results showed that the BR diet significantly reduced the number of aberrant
      crypt per focus and altered their distribution. In addition, DF of BR increased
      significantly the mucus secretion compared to control group. The use of the AOM
      as colon specific carcinogen substance altered the liver and lung architectures,
      whereas the presence of DF of BR could be a protective factor for these organs.

PMID- 24295707
TI  - Effect of the co-occurring olive oil and thyme extracts on the phenolic
      bioaccessibility and bioavailability assessed by in vitro digestion and cell
      models.
AB  - Olive oils flavoured with edible herbs have grown in popularity because of their
      added value and potential health benefits. However, the combined presence of
      different phytochemicals from olive oil and herbs requires study of their
      possible interactions during intestinal transport and metabolism. The aim of this
      study was firstly to evaluate the effect on bioaccessibility of the co-occurring
      bioactive compounds from olive oil and thyme through an in vitro digestion model
      of three extracts: olive extract (OE), thyme extract (TE) and a combination of
      both (OTE). The bioaccessible fractions were exposed to Caco-2 and HepG-2 cell
      models, as well as to a co-culture of both of these. Results indicated that the
      bioaccessibility of hydroxytyrosol was enhanced when OTE was digested. After Caco
      2 cells exposure, no significant differences were observed in hydroxytyrosol
      transport, whereas the main flavonoids from thyme seemed to undergo an enhanced
      basolateral permeation when both phenolic sources where exposed.

PMID- 24295708
TI  - Volatile constituents of commercial imported and domestic black-ripe table olives
      (Olea europaea).
AB  - Volatile constituents of commercial black-ripe table olives (Olea europaea) from
      the United States, Spain, Egypt and Morocco were analysed by gas chromatography
      and gas chromatography-mass spectrometry (GC-MS). Dynamic headspace sampling was
      used to isolate a variety of aldehydes, alcohols, esters, ketones, phenols,
      terpenes, norisoprenoids, and pyridines. Odour unit values, calculated from
      concentration and odour threshold data, indicate that the following compounds are
      major contributors to black-ripe table olive aroma: beta-damascenone, nonanal,
      (E)-dec-2-enal, 3-methylbutanal, ethyl benzoate, octanal, 2-methoxyphenol, 2
      methylbutanal and 2-methoxy-4-methylphenol. Imported olives contained a variety
      of fermentation derived volatiles that were not detected in domestic olives.
      Constituents such as ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, 3
      methylbutyl acetate, oct-1-en-3-one, ethyl hexanoate, (Z)-hex-3-enyl acetate,
      hexyl acetate, ethyl cyclohexanecarboxylate, benzyl acetate and 4-ethylphenol
      contributed to the odour of imported olives but were not detected in domestic
      olives. 

PMID- 24295709
TI  - Antioxidant activity and in vitro digestibility of dialdehyde starches as
      influenced by their physical and structural properties.
AB  - Dialdehyde starches (DASs) with different aldehyde contents were prepared by
      periodate oxidation of corn starch, and their antioxidant activity and
      digestibility were studied and related to their structural characteristics,
      including morphology, relative crystallinity, average molecular weights, swelling
      power and solubility. The results revealed that DASs were effective antioxidants
      as revealed by the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
      activity. A significant positive correlation (r>0.959, p<0.01) was found between
      the antioxidant effect and the aldehyde contents of DASs at all concentrations.
      The oxidation of starch increased the rapidly digestible starch (RDS) and
      resistant starch (RS) contents but reduced the amount of slowly digestible starch
      (SDS). Correlation analysis indicated that the amounts of RDS and RS were
      positively correlated to the aldehyde contents of DASs (r=0.973, p<0.01, and
      r=0.900, p<0.01), whilst the amount of SDS was negatively correlated to the
      aldehyde contents (r=-0.960, p<0.01). The structural characteristic also plays an
      important role for the antioxidant activity and digestibility of DASs. 

PMID- 24295710
TI  - Automated DNA extraction from pollen in honey.
AB  - In recent years, honey has become subject of DNA analysis due to potential risks
      evoked by microorganisms, allergens or genetically modified organisms. However,
      so far, only a few DNA extraction procedures are available, mostly time-consuming
      and laborious. Therefore, we developed an automated DNA extraction method from
      pollen in honey based on a CTAB buffer-based DNA extraction using the Maxwell 16
      instrument and the Maxwell 16 FFS Nucleic Acid Extraction System, Custom-Kit. We
      altered several components and extraction parameters and compared the optimised
      method with a manual CTAB buffer-based DNA isolation method. The automated DNA
      extraction was faster and resulted in higher DNA yield and sufficient DNA purity.
      Real-time PCR results obtained after automated DNA extraction are comparable to
      results after manual DNA extraction. No PCR inhibition was observed. The
      applicability of this method was further successfully confirmed by analysis of
      different routine honey samples. 

PMID- 24295711
TI  - Encapsulation of beta-carotene within ferritin nanocages greatly increases its
      water-solubility and thermal stability.
AB  - Carotenoids may play a number of potential health benefits for human. However,
      their use in food industry is limited mostly because of their poor water
      solubility and low thermal stability. Ferritins are widely distributed in nature
      with a shell-like structure which offers a great opportunity to improve the water
      solubility and thermal stability of the carotenoids by encapsulation. In this
      work, recombinant human H-chain ferritin (rHuHF) was prepared and used to
      encapsulate beta-carotene, a typical compound among carotenoids, by taking
      advantage of the reversible dissociation and reassembly characteristic of
      apoferritin in different pH environments. Results from high-performance liquid
      chromatography (HPLC), UV/Vis spectroscopy and transmission electron microscope
      (TEM) indicated that beta-carotene molecules were successfully encapsulated
      within protein cages with a beta-carotene/protein molar ratio of 12.4-1. Upon
      such encapsulation, these beta-carotene-containing apoferritin nanocomposites
      were water-soluble. Interestingly, the thermal stability of the beta-carotene
      encapsulated within apoferritin nanocages was markedly improved as compared to
      free beta-carotene. These new properties might be favourable to the utilisation
      of beta-carotene in food industry. 

PMID- 24295712
TI  - Determination of volatile thiols in virgin olive oil by derivatisation and LC
      HRMS, and relation with sensory attributes.
AB  - Volatile thiols were determined by derivatisation followed by ESI-LC-HRMS in
      twenty-five virgin olive oils (VOOs) pertaining to different commercial classes.
      4-Methoxy-2-methyl-2-butanethiol (4MMB) was quantified, and 3-methyl-2
      butenethiol and methanethiol were identified for the first time in VOO by non
      target analysis. In order to evaluate the influence of volatile thiols on VOO
      aroma, the sensory notes, defects and secondary attributes were determined in
      samples according to European regulation by an Official VOO Panel. A significant
      correlation was found between the concentration of 4MMB in VOO samples and the
      'fig tree leaf' sensory attribute. To confirm these results, 4MMB odour detection
      threshold and odour recognition were investigated. 

PMID- 24295713
TI  - Analysis of oestrogenic compounds in dairy products by hollow-fibre liquid-phase
      microextraction coupled to liquid chromatography.
AB  - In this work, the potential of a hollow-fibre liquid-phase microextraction (LPME)
      based method has been studied and validated for the extraction of a group of nine
      oestrogenic compounds four of them being natural (oestriol, 17beta-oestradiol,
      17alpha-oestradiol and oestrone), four being synthetic (17alpha
      ethynyloestradiol, diethylstilbestrol, dienestrol and hexestrol) and one
      metabolite (2-hydroxyoestradiol) in different dairy products (whole and skimmed
      natural yogurt, a probiotic yogurt-type drink and cheese). The methodology
      includes a prior protein precipitation with acidified acetonitrile for all
      samples and an additional defatting step with n-hexane for cheese, the matrix
      with the highest fat content. Later separation, determination and quantification
      were done by high-performance liquid chromatography coupled to a diode array
      detector and a fluorescence detector set in series. Calibration, sensitivity,
      precision and accuracy of the method were carried out in the selected matrices,
      providing good linearity, LODs in the low MUg/kg or MUg/L range, good precision
      and appropriate accuracy. 

PMID- 24295714
TI  - Antioxidant activity of Cod (Gadus morhua) protein hydrolysates: in vitro assays
      and evaluation in 5% fish oil-in-water emulsion.
AB  - Cod protein hydrolysates were fractionated according to the molecular mass into
      three fractions of >5 kDa, 3-5 kDa and <3 kDa using an ultrafiltration membrane
      system. The antioxidative activity of the crude hydrolysates and the fractions
      were investigated, both in in vitro assays (DPPH radical scavenging activity,
      reducing power, Fe2+ chelating activity and inhibition of lipid oxidation in
      liposome model system), and in 5% fish oil-in-water emulsions. The <3 kDa
      fractions had very good radical scavenging activity, Fe2+ chelating activity and
      reducing power while the fraction 3-5 kDa resulted in higher protection against
      oxidation in the liposome model system. When tested in 5% oil-in-water emulsions,
      all the fractions, including the crude protein hydrolysate, were able to protect
      fish oil against oxidation in an iron induced oxidation system. However, none of
      the peptide fractions were effective in preventing tocopherol loss and showed no
      tocopherol sparing property. Volatile oxidation products showed an interaction
      between the aldehydes and the protein/peptides added in the emulsions, and this
      needs further investigation.

PMID- 24295715
TI  - Non-steroidal anti-inflammatory drug modulates oxidative stress and calcium ion
      levels in the neutrophils of patients with primary dysmenorrhea.
AB  - Primary dysmenorrhea is a common inflammatory disease with an uncertain
      pathogenesis, although one consistent finding is increased neutrophil activity.
      We aimed to investigate the effects of a non-steroidal anti-inflammatory drug
      (NSAID) on oxidative stress and Ca2+ levels in neutrophils from patients with
      primary dysmenorrhea. Blood samples were obtained for neutrophil isolation from
      six female patients with primary dysmenorrhea (patients) and six healthy female
      subjects. The NSAID (diclofenac) was taken daily by the patient group for 6 weeks
      before a second blood sample was taken. Neutrophils isolated after diclofenac
      treatment were investigated in three settings: (1) after incubation with
      verapamil and diltiazem (V+D), (2) after incubation with 2-aminoethoxydiphenyl
      borate (2-APB), and (3) with neither exposure. Neutrophil lipid peroxidation and
      stimulated intracellular Ca2+ levels were higher in the patients than in the
      controls, although their levels were reduced after six weeks of treatment with
      diclofenac. Ca2+ levels from neutrophils obtained after diclofenac treatment were
      further decreased after incubation with V+D or 2-APB, compared with those exposed
      to neither agent. Neutrophil glutathione peroxidase and total antioxidant status
      were lower in the patients than in the controls and higher post-treatment with
      diclofenac. Reduced glutathione levels were similar in the control, patient, and
      treatment groups. In conclusion, we observed the importance of Ca2+ influx into
      the neutrophils and oxidative stress in the pathogenesis of the patients with
      primary dysmenorrhea. The NSAID diclofenac appeared to provide a protective
      effect against oxidative stress and Ca2+ entry through modulation of neutrophil
      VGCC and TRP calcium channels.

PMID- 24295716
TI  - Use of volatile anesthetics during cardiopulmonary bypass: a systematic review of
      adverse events.
AB  - OBJECTIVES: Recently, evidence of reduction in mortality due to the use of
      volatile agents during cardiac surgery led to an increase in their use during
      cardiopulmonary bypass (CPB). Because this technique could be beneficial to
      patients, but might present several hazards to new users, the authors decided to
      perform a systematic review of the main problems and complications. DESIGN:
      Systematic literature review. SETTING: Hospital. PARTICIPANTS: Adults undergoing
      cardiac surgery with use of volatile anesthetic agents during CPB. INTERVENTION:
      Several databases were searched for pertinent studies to identify all reports on
      the adverse events of using volatile agents during CPB and all randomized
      controlled trials using volatile agents during CPB. MEASUREMENTS AND MAIN
      RESULTS: Six nonrandomized trials reporting adverse events or complications with
      the use of volatile agents during CPB for cardiac surgery were identified: 2
      reporting low transfer of isoflurane to the blood with diffusion membrane
      oxygenators; 2 reporting iatrogenic causes of damage after spilling liquid
      isoflurane onto the surface of the membrane oxygenators while filling the
      vaporizer; and 2 suggesting that the use of volatile agents during CPB increased
      the pollution of the room and the risk of occupational exposure of the operating
      room staff. On the other hand, no adverse event was reported in 19 studies that
      randomized 1,195 patients to receive isoflurane, desflurane, or sevoflurane
      during CPB. CONCLUSION: It is mandatory for industry to provide safe and easy-to
      use devices to administer volatile agents during CPB with the standard membrane
      oxygenators.

PMID- 24295717
TI  - Earlier versus later tracheostomy in patients with respiratory failure after
      cardiac surgery in the United States.
AB  - OBJECTIVES: The objective of this study was to evaluate the impact of timing of
      tracheostomy on outcomes of patients with respiratory failure after cardiac
      surgery. DESIGN: Retrospective analysis of national database. SETTING: United
      States hospitals. PARTICIPANTS: A weighted estimate of 2,063,227 patients
      (475,773 case records) undergoing cardiac surgery identified from the Nationwide
      Inpatient Sample between 2002-2010 INTERVENTIONS: Early versus late tracheostomy.
      MEASUREMENTS AND MAIN RESULTS: The incidence of postoperative respiratory failure
      was 7.8%. The strongest independent predictors of respiratory failure included
      female gender (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.28-1.31), age
      (OR 1.13 for each decade, 95% CI 1.12-1.13), chronic obstructive airways disease
      (OR 2.16, 95% CI 2.13-2.19), chronic renal insufficiency (OR 2.28, 95% CI 2.25
      2.31), and valve surgery (OR 1.62, 95% CI 1.6-1.64). Tracheostomy was performed
      in 22.9% of patients with respiratory failure; 13.6% of tracheostomies were
      performed within 5 days of surgery (or within 5 days of intubation in patients
      who underwent reintubation), and 20.5% were performed on postoperative day 21 or
      later. Compared with tracheostomy performed within 5 days of intubation, there
      was a near-stepwise increase in risk of mortality with delayed tracheostomy
      performed between days 11-15 (OR 1.29, 95% CI 1.16-1.43), days 16-20 (OR 1.25,
      95% CI 1.11-1.41), and day 21 or later (OR 1.53, 95% CI 1.37-1.71). CONCLUSIONS:
      In this analysis of outcomes of patients with respiratory failure after cardiac
      surgery in the United States, deferring tracheostomy did not appear to improve
      patient outcomes after cardiac surgery.

PMID- 24295718
TI  - Preoperative urinary neutrophil gelatinase-associated lipocalin and outcome in
      high-risk heart failure patients undergoing cardiac surgery.
AB  - OBJECTIVE: To investigate the ability of early urinary neutrophil gelatinase
      associated lipocalin to predict postoperative complications in adult patients
      with ventricular dysfunction undergoing cardiac surgery. DESIGN: Prospective
      observational study. SETTING: Single-center study, university hospital.
      PARTICIPANTS: Fifty-six adult high-risk cardiac surgical patients with
      preoperative cardiac failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Demographic and clinical characteristics were obtained, and neutrophil gelatinase
      associated lipocalin was measured at baseline and at several time points after
      surgery. Patient characteristics and neutrophil gelatinase-associated lipocalin
      levels were related to renal and patient outcome. On multivariate analyses,
      preoperative urinary neutrophil gelatinase-associated lipocalin was an
      independent predictor of length of intensive care stay (p = 0.004) and in
      hospital stay (p = 0.04), but not of acute kidney injury or renal replacement
      therapy and was not associated with baseline renal function. CONCLUSIONS: In a
      cohort of high-risk cardiac surgery patients, preoperative urinary neutrophil
      gelatinase-associated lipocalin value provided prognostic information that was
      independent of the onset of acute kidney injury or of preoperative renal
      function.

PMID- 24295719
TI  - Incidence and outcomes of heparin-induced thrombocytopenia in patients undergoing
      cardiac surgery in North America: an analysis of the nationwide inpatient sample.
AB  - OBJECTIVES: The objective of this study was to quantify the impact of heparin
      induced thrombocytopenia (HIT) on outcomes after cardiac surgery. DESIGN:
      Retrospective analysis of national database. SETTING: United States hospitals.
      PARTICIPANTS: Patients identified from 186,771 discharge records undergoing
      cardiac surgery from the Nationwide Inpatient Sample between 2009 and 2010.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heparin-induced
      thrombocytopenia was diagnosed in 506 (0.3%), and secondary thrombocytopenia was
      diagnosed in 16,809 (8.7%). Operative mortality was 11.1% in patients with HIT
      compared to 4.5% for patients without thrombocytopenia (p<0.001) and 4.0% for
      patients with a diagnosis of secondary thrombocytopenia (p<0.001). After
      adjusting for baseline patient comorbidity, the strongest independent predictors
      of HIT in patients undergoing cardiac surgery were female gender (OR 1.4, 95%
      confidence interval [CI] 1.28-1.48), congestive heart failure (OR 1.8, 95% CI
      1.71-1.98), cardiac insufficiency (OR 2.2, 95% CI 1.97-2.39), atrial fibrillation
      (OR 1.4, 95% CI 1.30-1.51), liver disease (OR 2.2, 95% CI 1.96-2.50), and chronic
      renal failure (OR 1.4, 95% CI 1.30-1.51). HIT was associated with significantly
      increased risk of major adverse postoperative outcomes including death (OR 1.5,
      95% CI 1.3-1.7), stroke (OR 2.4, 95% CI 1.9-3.1), amputation (OR 7.46, 95% CI 4.0
      14.0), and acute renal failure (OR 2.3, 95% CI 2.1-2.5), respiratory failure (OR
      1.9, 95% CI 1.8-2.1), and need for tracheostomy (OR 2.7, 95% CI 2.3-3.1).
      CONCLUSIONS: Heparin-induced thrombocytopenia is associated with a 50% increase
      in early mortality, and most patients with this diagnosis experience major
      postoperative morbidity or functional deficits.

PMID- 24295720
TI  - The use of real-time three-dimensional transesophageal echocardiography for
      percutaneous closure of a ruptured sinus of valsalva aneurysm.

PMID- 24295721
TI  - General anesthesia versus sedation for implantation of a biventricular pacing
      device for cardiac resynchronization therapy.
AB  - OBJECTIVE: Heart failure carries significant risk for major noncardiac surgery.
      Whether this risk is transferable to minor surgery is less well-documented. Thus,
      the aim of this study was to assess the outcome of a contemporary cohort of heart
      failure patients undergoing cardiac resynchronization therapy (CRT) device
      insertion under general anesthesia or sedation. DESIGN: Retrospective
      observational study. SETTING: Tertiary cardiac specialist hospital. PARTICIPANTS:
      Heart failure patients. INTERVENTIONS: CRT insertion under general anesthesia or
      sedation. MEASUREMENTS AND MAIN RESULTS: Anesthesia, heart failure, and outcome
      data were collected on a consecutive series of patients having CRT device
      insertion between 2002 and 2010. A total of 242 patients were managed by the
      anesthesia department during the study period. After exclusion criteria were
      applied, data for 183 patients were analyzed. Immediate perioperative (<24 hours)
      mortality was zero; 30-day mortality of 138 patients was 2.2%. One patient (0.5%)
      required unplanned intensive care admission. A comparison was made between the
      sedation (n = 76) group and the general anesthesia (GA) group (n = 107). When
      compared with the sedation group, the GA group had more intraoperative
      hypotension (26.2% versus 4.0%, p<0.00001). There was no difference between the
      GA and sedation groups with regard to 30-day mortality (1.4% versus 3.1%, p =
      0.57), unplanned intensive care admission (0% versus 1.3%, p = 0.42), and length
      of stay in days (3 versus 3, p = 0.82). CONCLUSION: The authors found that
      patients with heart failure undergoing CRT insertion with concurrent general
      anesthesia or sedation had minimal immediate perioperative risk and that there
      was no difference in postoperative outcome between general anesthesia and
      sedation.

PMID- 24295722
TI  - Safety and utility of noninvasive ventilation during deep sedation for catheter
      ablation of atrial fibrillation.

PMID- 24295723
TI  - "Methylene blue should be relegated to rescue use and not as first-line therapy"
      cannot become a paradigm.

PMID- 24295724
TI  - Assessing the impact of dairy waste lagoons on groundwater quality using a
      spatial analysis of vadose zone and groundwater information in a coastal phreatic
      aquifer.
AB  - Dairy waste lagoons are considered to be point sources of groundwater
      contamination by chloride (Cl(-)), different nitrogen-species and
      pathogens/microorganisms. The objective of this work is to introduce a
      methodology to assess the past and future impacts of such lagoons on regional
      groundwater quality. The method is based on a spatial statistical analysis of Cl(
      ) and total nitrogen (TN) concentration distributions in the saturated and the
      vadose (unsaturated) zones. The method provides quantitative data on the relation
      between the locations of dairy lagoons and the spatial variability in Cl(-) and
      TN concentrations in groundwater. The method was applied to the Beer-Tuvia
      region, Israel, where intensive dairy farming has been practiced for over 50
      years above the local phreatic aquifer. Mass balance calculations accounted for
      the various groundwater recharge and abstraction sources and sinks in the entire
      region. The mass balances showed that despite the small surface area covered by
      the dairy lagoons in this region (0.8%), leachates from lagoons have contributed
      6.0% and 12.6% of the total mass of Cl(-) and TN (mainly as NO3(-)-N) added to
      the aquifer. The chemical composition of the aquifer and vadose zone water
      suggested that irrigated agricultural activity in the region is the main
      contributor of Cl(-) and TN to the groundwater. A low spatial correlation between
      the Cl(-) and NO3(-)-N concentrations in the groundwater and the on-land location
      of the dairy farms strengthened this assumption, despite the dairy waste lagoon
      being a point source for groundwater contamination by Cl(-) and NO3(-)-N. Mass
      balance calculations, for the vadose zone of the entire region, indicated that
      drying of the lagoons would decrease the regional groundwater salinization
      process (11% of the total Cl(-) load is stored under lagoons). A more
      considerable reduction in the groundwater contamination by NO3(-)-N is expected
      (25% of the NO3(-)-N load is stored under lagoons). Results demonstrate that
      analyzing vadose zone and groundwater data by spatial statistical analysis
      methods can significantly contribute to the understanding of the relations
      between groundwater contaminating sources, and to assessing appropriate
      remediation steps. 

PMID- 24295725
TI  - Personal networks and private forestry in Minnesota.
AB  - Personal networks affect the flow information and behavior through social groups.
      We investigated the role of personal relationships in the flow of information and
      adoption of sustainable forest management behavior by private forest landowners.
      Among the 1767 owners of 20 or more acres of Minnesota forest land surveyed, 90%
      have received forestry information from at least one source including 65% from a
      peer and 53% from a professional forester. Forestry information personal network
      size ranged from 0 to 14 with a mean of 2.92. Network diversity, expressed as the
      number of different types of information sources within the network, was
      relatively high relative to network size, suggesting that most landowners value
      diverse perspectives, despite reporting fairly small networks. Larger acreage
      owners, management plan holders, and frequent visitors to their forest land had
      significantly larger and more diverse networks. Network size and diversity were
      statistically unrelated to ownership tenure, landowner age, and resident/absentee
      status. Significantly more respondents named a peer or a professional as their
      most helpful source than other source categories. Satisfaction with forestry
      information networks was positively associated with network size and diversity,
      further suggesting that landowners prefer information from a variety of different
      sources. The results suggest that landowner education designed to foster peer
      learning and relationship building between landowners, foresters, loggers, and
      other groups may promote adoption of sustainable forest management practices. 

PMID- 24295726
TI  - The paradox of FGFR3 signaling in skeletal dysplasia: why chondrocytes growth
      arrest while other cells over proliferate.
AB  - Somatic mutations in receptor tyrosine kinase FGFR3 cause excessive cell
      proliferation, leading to cancer or skin overgrowth. Remarkably, the same
      mutations inhibit chondrocyte proliferation and differentiation in developing
      bones, resulting in skeletal dysplasias, such as hypochondroplasia,
      achondroplasia, SADDAN and thanatophoric dysplasia. A similar phenotype is
      observed in Noonan syndrome, Leopard syndrome, hereditary gingival fibromatosis,
      neurofibromatosis type 1, Costello syndrome, Legius syndrome and
      cardiofaciocutaneous syndrome. Collectively termed RASopathies, the latter
      syndromes are caused by germline mutations in components of the RAS/ERK MAP
      kinase signaling pathway. This article considers the evidence suggesting that
      FGFR3 activation in chondrocytes mimics the activation of major oncogenes
      signaling via the ERK pathway. Subsequent inhibition of chondrocyte proliferation
      in FGFR3-related skeletal dysplasias and RASopathies is proposed to result from
      activation of defense mechanisms that originally evolved to safeguard mammalian
      organisms against cancer. 

PMID- 24295727
TI  - Changing patterns of recurrent disease in colorectal cancer.
AB  - BACKGROUND: Due to changes in staging, (neo)-adjuvant treatment and surgical
      techniques for colorectal cancer (CRC), it is expected that the recurrence
      pattern will change as well. This study aims to report the current incidence of,
      and time to recurrent disease (RD), further the localization(s) and the
      eligibility for successive curative treatment. METHODS: A consecutive cohort of
      CRC patients, whom were routinely staged with CT and underwent curative treatment
      according to the national guidelines, was analyzed (n = 526). RESULTS: After a
      mean and median FU of 39 months, 20% of all patients and 16% of all AJCC stage 0
      III patients had developed RD. The annual incidences were the highest in the
      first two years but tend to retain in the succeeding years for stage 0-III
      patients. The majority of RD was confined to one organ (58%) and 28% of these
      patients were again treated with curative intent. CONCLUSIONS: In follow-up
      nowadays, less recurrences are found than reported in historical studies but
      these can more often be treated with curative intent. A main cause for the
      decreased incidence of RD, next to improvements in treatment, is probably stage
      shift elicited by pre-operative staging. The outcomes support continuation of
      follow-up in colorectal cancer.

PMID- 24295729
TI  - The effect of priming with a love concept on blood donation promise.
AB  - This field study on blood donor behavior tests the effectiveness of semantic
      priming on donor intention and commitment. Using face-to-face interactions,
      participants were primed with the concept of love and solicited to promise blood
      to the French National Blood Bank. Results showed a significant effect on
      willingness to donate blood and on donor commitment. The relatively simple and
      easily implemented technique used in this study could be of interest in improving
      performance of recruitment and retention campaigns. 

PMID- 24295728
TI  - Exposure to nicotine enhances its subsequent self-administration: contribution of
      nicotine-associated contextual stimuli.
AB  - Contextual stimuli present during nicotine exposure can come to act as
      conditioned stimuli and have been shown to play an important role in ongoing
      nicotine self-administration. In the present study, we characterized the effects
      of contextual stimuli previously paired with non-contingent nicotine exposure
      injections on subsequent nicotine self-administration. Rats were exposed to five
      injections of either saline or nicotine (0.4 mg/kg, i.p.) in either their home
      cage or a self-administration chamber with the levers retracted. Two weeks later,
      they were allowed to self-administer nicotine (30 MUg/kg/infusion, IV) under
      fixed ratio (FR) schedules of reinforcement across 12 consecutive sessions.
      Lastly, responding under a progressive ratio (PR) schedule was assessed. Rats
      exposed to nicotine in the self-administration chamber subsequently increased
      their intake of nicotine across the FR test days, obtaining more infusions on
      average by days 7-12 compared to their saline exposed controls. This increase was
      not due to nicotine exposure alone as rats exposed to nicotine in the home cage
      did not show this effect. It was also not due to differences in the final ratio
      achieved between nicotine and saline exposed rats. Although rats exposed to
      nicotine in the self-administration chambers displayed reduced discrimination
      between the active and inactive levers during FR testing, they showed increased
      motivation to self-administer nicotine under the PR schedule. These results
      indicate that exposure to nicotine can enhance its subsequent self-administration
      and highlight the contribution of nicotine-associated contextual stimuli to the
      work output rats ultimately emit to obtain the drug.

PMID- 24295730
TI  - Ontogenetic manganese exposure with perinatal 6-OHDA lesioning alters behavioral
      responses of rats to dopamine D1 and D2 agonist treatments.
AB  - The effect of neonatal manganese (Mn) exposure in a 6-hydroxydopamine (6-OHDA)
      rat model of Parkinson's disease was investigated. Pregnant Wistar rats were
      given drinking water with 10,000 ppm of Manganese (MnCl2.4H2O) from the time of
      conception until weaning on the 21st day after delivery. Control rats consumed
      tap water. Three days after the birth, other groups of neonatal rat pups were
      pretreated with desipramine (20 mg/kg ip 1h) prior to bilateral ICV
      administration of 6-OHDA or its vehicle, saline-ascorbic (0.1%) (control). Two
      months after the birth, striatal dopamine and homovanilic acid efflux measured by
      an in vivo microdialysis method were reduced in rats lesioned with 6-OHDA. Co
      exposure to perinatal Mn did not modify neurotransmission alterations. However,
      there were prominent abnormalities in behavioral testing in rats perinatally
      exposed to Mn and treated neonatally with 6-OHDA. These findings demonstrate that
      although Mn did not further damage neurotransmitter activity in the neostriatum,
      ontogenetic exposure to Mn enhances the behavioral toxicity to 6-OHDA.

PMID- 24295731
TI  - Protective effects of timosaponin B-II on high glucose-induced apoptosis in human
      umbilical vein endothelial cells.
AB  - This study was designed to investigate the action of timosaponin B-II, a main
      bioactive compound in Anemarrhena asphodeloides Bunge, on the prevention from
      high glucose-induced cytotoxicity and apoptosis in human umbilical vein
      endothelial cells (HUVECs) and the potential mechanisms involved. The results
      showed that compared with the normal control group, exposure of HUVECs to high
      glucose media for 72 h resulted in a significant increase in lactates
      dehydrogenise release, reactive oxygen species production, Caspase-3 activity and
      the percentage of apoptotic cells (p<0.01). However, pretreatment with
      timosaponin B-II significantly increased the viability of HUVECs and decreased
      lactates dehydrogenise release, Caspase-3 activity and the apoptosis rate in a
      concentration-dependent manner (p<0.05). In addition, timosaponin B-II notably
      decreased the amount of reactive oxygen species and malondialdehyde, as well as
      promoted glutathione peroxidase activity, endothelial nitric oxide synthase
      activity and nitric oxide release (p<0.05). These results suggest that
      timosaponin B-II has the antiapoptotic effect in endothelial cells through
      inhibition of high glucose-induced oxidative stress and has the potential for
      preventing diabetic cardiovascular complications.

PMID- 24295732
TI  - Ejaculatory sperm production in non-obstructive azoospermic patients with a
      history of negative testicular biopsy after the administration of an aromatase
      inhibitor: report of two cases.

PMID- 24295733
TI  - Rapamycin improves sociability in the BTBR T(+)Itpr3(tf)/J mouse model of autism
      spectrum disorders.
AB  - Overactivation of the mammalian target of rapamycin (mTOR) has been implicated in
      the pathogenesis of syndromic forms of autism spectrum disorders (ASDs), such as
      tuberous sclerosis complex, neurofibromatosis 1, and fragile X syndrome.
      Administration of mTORC1 (mTOR complex 1) inhibitors (e.g. rapamycin) in
      syndromic mouse models of ASDs improved behavior, cognition, and neuropathology.
      However, since only a minority of ASDs are due to the effects of single genes
      (~10%), there is a need to explore inhibition of mTOR activity in mouse models
      that may be more relevant to the majority of nonsyndromic presentations, such as
      the genetically inbred BTBR T(+)Itpr3(tf)/J (BTBR) mouse model of ASDs. BTBR mice
      have social impairment and exhibit increased stereotypic behavior. In prior work,
      d-cycloserine, a partial glycineB site agonist that targets the N-methyl-d
      aspartate (NMDA) receptor, was shown to improve sociability in both Balb/c and
      BTBR mouse models of ASDs. Importantly, NMDA receptor activation regulates mTOR
      signaling activity. The current study investigated the ability of rapamycin
      (10mg/kg, i.p.*four days), an mTORC1 inhibitor, to improve sociability and
      stereotypic behavior in BTBR mice. Using a standard paradigm to assess mouse
      social behavior, rapamycin improved several measures of sociability in the BTBR
      mouse, suggesting that mTOR overactivation represents a therapeutic target that
      mediates or contributes to impaired sociability in the BTBR mouse model of ASDs.
      Interestingly, there was no effect of rapamycin on stereotypic behaviors in this
      mouse model. 

PMID- 24295734
TI  - HIC1 silencing in triple-negative breast cancer drives progression through
      misregulation of LCN2.
AB  - The tumor suppressor gene HIC1 is frequently deleted or epigenetically silenced
      in human cancer, where its restoration may improve cancer prognosis. Here, we
      report results illuminating how HIC1 silencing alters effect or signals in triple
      negative breast cancer (TNBC), which are crucial for its pathogenesis. HIC1
      expression was silenced only in TNBC compared with other molecular subtypes of
      breast cancer. Restoring HIC1 expression in TNBC cells reduced cell migration,
      invasion, and metastasis, whereas RNAi-mediated silencing of HIC1 in
      untransformed human breast cells increased their invasive capabilities.
      Mechanistic investigations identified the small-secreted protein lipocalin-2
      (LCN2), as a critical downstream target of HIC1 in TNBC cells. Elevating LCN2
      expression in cells expressing HIC1 partially rescued its suppression of cell
      invasion and metastasis. Notably, autocrine secretion of LCN2 induced by loss of
      HIC1 activated the AKT pathway through the neutrophil gelatinase-associated
      lipocalin receptor, which is associated with TNBC progression. Taken together,
      our findings revealed that the HIC1-LCN2 axis may serve as a subtype-specific
      prognostic biomarker, providing an appealing candidate target for TNBC therapy.

PMID- 24295735
TI  - Comprehensive low-dose imaging of carotid and coronary arteries with a single
      injection dual-source CT angiography protocol.
AB  - AIM: To assess the feasibility of a fast single-bolus combined carotid and
      coronary computed tomography angiography (CTA) protocol in asymptomatic patients.
      MATERIALS AND METHODS: Thirty-three consecutive patients (18 women and 15 men)
      with a median age of 61 +/- 14 years old (range 37-87 years) with known or
      suspected atherosclerotic disease were enrolled in this prospective study. A
      single breath-hold, single biphasic injection protocol (50 ml at 3 ml/s, 50 ml at
      5 ml/s, 50 ml saline flush at 5 ml/s) was used for combined CTA imaging of the
      supra-aortic (SAA) and coronary arteries (CA) on a 64-slice dual-source CT (DSCT)
      machine. Helical CTA acquisition of the SAA was followed by prospective
      electrocardiography (ECG)-triggered coronary CTA. Subjective (four-point scale)
      image quality and objective signal-to-noise (SNR) and contrast-to-noise (CNR)
      measurements were performed. Vascular disease was graded on a four-point scale
      (grade 1: absent; grade 2: mild, grade 3: moderate; grade 4: severe). The
      radiation dose was recorded for each patient. RESULTS: The average enhancement
      and subjective quality score of SAA and CA segments were 396 HU/358 HU and 1.2 +/
      0.3/1.72 +/- 0.4, respectively. The SNR was 27.1 +/- 1.7 in the SAA and 21.6 +/-
      1.6 in the CA (p < 0.0001). The CNR was 18.1 +/- 1.2 and 15.9 +/- 1.8,
      respectively (p = 0.4). Four percent of SAA and 14% of CA segments (mostly due to
      peri-venous streak artefacts and small calibre, respectively) produced non
      diagnostic images. SAA findings were as follows: 26/33 (79%) patients showed no
      disease and 6/33 (18%) had grade 2 and 1/33 (3%) had grade 3 disease. CA findings
      were as follows: 25/33 (76%) showed no disease and 6/33 (18%) patients had grade
      2 and 2/33 (6%) had grade 3 disease. Five patients had disease in both districts.
      The average radiation dose for the combined CTA angiogram was 4.3 +/- 0.6 mSv.
      CONCLUSION: A fast, low-dose combined DSCT angiography protocol appears
      technically feasible for imaging carotid and coronary atherosclerotic disease.

PMID- 24295736
TI  - Femoral head avascular necrosis: a frequently missed incidental finding on
      multidetector CT.
AB  - AIM: To determine the incidence of missed femoral head avascular necrosis (AVN)
      on pelvic computed tomography (CT) performed for clinical indications other than
      assessment for AVN. MATERIALS AND METHODS: The study was a Health Insurance
      Portability and Accountability Act (HIPAA)-compliant retrospective study. The
      picture archiving and communication system (PACS) database was queried for
      patients with diagnosis of femoral head AVN on magnetic resonance imaging (MRI),
      who also underwent pelvic multidetector CT after or <30 days before the MRI
      examination. The MRI and CT images of 144 hips of 72 patients (39 patients with
      reported AVN on MRI and 33 age-matched controls; mean age = 60 years, 28 male, 44
      female), were reviewed in consensus by two readers in a randomized, blinded
      manner. Using MRI-proven CT-visible AVN as a reference standard, the incidence of
      missed AVN on initial CT interpretation was determined. RESULTS: Readers
      confirmed AVN in 33 patients on the MRI images. Nine hips with AVN underwent
      joint replacement of the affected joint(s) prior to subsequent CT and were
      excluded. Forty-three MRI-proven AVN cases in 28 patients (15 bilateral, 13
      unilateral) were available for analysis. The study readers diagnosed 35/43 (81%)
      MRI-proven AVN cases in 22/28 (79%) patients. Four of the 35 (11%) cases of MRI
      proven, CT-visible AVN were prospectively reported in 3/22 (14%) patients at
      initial clinical interpretation, with a miss rate of 89% per hip and 86% per
      patient. CONCLUSION: Multidetector CT has high accuracy for detection of AVN;
      however, this is frequently missed as an incidental finding (89% missed in the
      present study). Assessment for signs of femoral AVN should be part of routine
      search pattern in interpretation of pelvic CT.

PMID- 24295737
TI  - Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium
      signaling.
AB  - Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of
      reproduction. We investigated the role of kisspeptin-stimulated KISS1R
      internalization, recycling, and degradation in the modulation of KISS1R
      signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1-7 cells
      expressing KISS1R resulted in a biphasic increase in intracellular Ca(2+)
      ([Ca(2+)]i), with a rapid acute increase followed by a more sustained second
      phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled
      receptor, resulted in a much smaller second-phase [Ca(2+)]i response. The KISS1R
      mediated second-phase [Ca(2+)]i response was abolished by removal of kisspeptin
      from cell culture medium. Notably, the second-phase [Ca(2+)]i response was also
      inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit
      receptor internalization and recycling, suggesting that KISS1R trafficking
      contributes to the sustained [Ca(2+)]i response. We further demonstrated that
      KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next
      investigated the fate of the internalized kisspeptin-KISS1R complex. Most
      internalized kisspeptin was released extracellularly in degraded form within 1
      hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex.
      Using a biotinylation assay, we demonstrated that degradation of cell surface
      KISS1R was much slower than that of the internalized ligand, suggesting
      dissociated processing of the internalized kisspeptin-KISS1R complex. Taken
      together, our results suggest that the sustained calcium response to kisspeptin
      is dependent on the continued presence of extracellular ligand and is the result
      of dynamic KISS1R trafficking. 

PMID- 24295739
TI  - Modulation of sodium-bicarbonate co-transporter (SLC4A4/NBCe1) protein and mRNA
      expression in rat's uteri by sex-steroids and at different phases of the oestrous
      cycle.
AB  - Oestrogen-induced uterine fluid sodium (Na(+)) and bicarbonate (HCO3(-))
      secretion may involve SLC4A4. We hypothesized that uterine SLC4A4 expression
      changes under different sex-steroid influence, therefore may account for the
      fluctuation in uterine fluid Na(+) and HCO3(-) content throughout the oestrous
      cycle. The aim of this study is to investigate the differential effects of sex
      steroids and oestrous cycle phases on uterine SLC4A4 expression. METHODS: Adult
      female WKY rats were ovariectomised and treated with different doses of 17beta
      oestradiol (E2) (0.2, 2, 20 and 50 MUg/ml/day) or progesterone (P4) (4 mg/ml/day)
      for three consecutive days and 3 days treatment with 0.2 MUg/ml/day E2 followed
      by another 3 days with P4 to mimic the hormonal changes in early pregnancy.
      Oestrous cycle phases in intact, non-ovariectomised rats were determined by
      vaginal smear. The animals were then sacrificed and uteri were removed for
      protein and mRNA expression analyses by Western blotting and Real Time PCR,
      respectively. SLC4A4 distribution was observed by immunohistochemistry. RESULTS:
      Treatment with increasing E2 doses resulted in a dose-dependent increase in
      SLC4A4 protein expression. High SLC4A4 protein and mRNA expression can be seen at
      estrus. SLC4A4 is distributed mainly at the apical as well as basolateral
      membranes of the luminal and glandular epithelia following E2 treatment and at
      Es. Meanwhile, SLC4A4 expression was reduced following P4 treatment and was low
      at diestrus. CONCLUSION: High SLC4A4 expression under estrogen dominance may
      contribute to the increase in uterine fluid Na(+) and HCO3(-) content, while its
      low expression under P4 dominance may result in vice versa.

PMID- 24295740
TI  - First finding of genetic and antigenic diversity in 1b-BVDV isolates from
      Argentina.
AB  - Infection with Bovine Viral Diarrhea Viruses (BVDV) in cattle results in a wide
      range of clinical manifestations, ranging from mild respiratory disease to fetal
      death and mucosal disease, depending on the virulence of the virus and the immune
      and reproductive status of the host. In this study 30 Argentinean BVDV isolates
      were characterized by phylogenetic analysis. The isolates were genotyped based on
      comparison of the 5' untranslated region (5' UTR) and the E2 gene. In both
      phylogenetic trees, 76% of the viruses were assigned to BVDV 1b, whereas BVDV 1a,
      2a and 2b were also found. Eight of the BVDV 1b isolates were further
      characterized by cross-neutralization tests using guinea pig antisera and sera
      from bovines vaccinated with two different commercial vaccines. The results
      demonstrated the presence of a marked antigenic diversity among Argentinean BVDV
      isolates and suggest the need to incorporate BVDV 1b isolates in diagnostic
      strategies. 

PMID- 24295741
TI  - Characterization of the hepcidin gene in eight species of bats.
AB  - Hemochromatosis, or iron storage disease, has been associated with significant
      liver disease and mortality in captive Egyptian fruit bats (Rousettus
      aegyptiacus). The physiologic basis for this susceptibility has not been
      established. In humans, a deficiency or resistance to the iron regulatory
      hormone, hepcidin has been implicated in the development of hereditary
      hemochromatosis. In the present study, we compared the coding sequence of the
      hepcidin gene in eight species of bats representing three distinct taxonomic
      families with diverse life histories and dietary preferences. Bat hepcidin mRNA
      encoded a 23 amino acid signal peptide, a 34 or 35 amino acid pro-region, and a
      25 amino acid mature peptide, similar to other mammalian species. Differences in
      the sequence of the portion of the hepcidin gene that encodes the mature peptide
      that might account for the increased susceptibility of the Egyptian fruit bat to
      iron storage disease were not identified. Variability in gene sequence
      corresponded to the taxonomic relationship amongst species. 

PMID- 24295738
TI  - Minireview: role of orphan nuclear receptors in cancer and potential as drug
      targets.
AB  - The nuclear orphan receptors for which endogenous ligands have not been
      identified include nuclear receptor (NR)0B1 (adrenal hypoplasia congenita
      critical region on chromosome X gene), NR0B2 (small heterodimer partner), NR1D1/2
      (Rev-Erbalpha/beta), NR2C1 (testicular receptor 2), NR2C2 (testicular receptor
      4), NR2E1 (tailless), NR2E3 (photoreceptor-specific NR [PNR]), NR2F1 chicken
      ovalbumin upstream promoter transcription factor 1 (COUP-TFI), NR2F2 (COUP-TFII),
      NR2F6 (v-erbA-related protein), NR4A1 (Nur77), NR4A2 (Nurr1), NR4A3 (Nor1), and
      NR6A1 (GCNF). These receptors play essential roles in development, cellular
      homeostasis, and disease including cancer where over- or underexpression of some
      receptors has prognostic significance for patient survival. Results of receptor
      knockdown or overexpression in vivo and in cancer cell lines demonstrate that
      orphan receptors exhibit tumor-specific pro-oncogenic or tumor suppressor-like
      activity. For example, COUP-TFII expression is both a positive (ovarian) and
      negative (prostate and breast) prognostic factor for cancer patients; in
      contrast, the prognostic activity of adrenal hypoplasia congenita critical region
      on chromosome X gene for the same tumors is the inverse of COUP-TFII. Functional
      studies show that Nur77 is tumor suppressor like in acute leukemia, whereas
      silencing Nur77 in pancreatic, colon, lung, lymphoma, melanoma, cervical,
      ovarian, gastric, and some breast cancer cell lines induces one or more of
      several responses including growth inhibition and decreased survival, migration,
      and invasion. Although endogenous ligands for the orphan receptors have not been
      identified, there is increasing evidence that different structural classes of
      compounds activate, inactivate, and directly bind several orphan receptors. Thus,
      the screening and development of selective orphan receptor modulators will have
      important clinical applications as novel mechanism-based agents for treating
      cancer patients overexpressing one or more orphan receptors and also for combined
      drug therapies. 

PMID- 24295742
TI  - Analytic validation and comparison of three commercial immunoassays for
      measurement of plasma atrial/A-type natriuretic peptide concentration in horses.
AB  - Measurement of atrial/A-type natriuretic peptide (ANP) concentrations may be of
      use for assessment of cardiac disease, and reliable data on the analytic
      performance of available assays are needed. To assess the suitability for
      clinical use of commercially available ANP assays, intra-assay and inter-assay
      coefficient of variation and dilution parallelism were calculated for three
      immunoassays (RIAPen, RIAPhoen, and an ELISAPen) using blood samples from healthy
      and diseased horses to cover a wide range of ANP concentrations. Further,
      agreement between assays was assessed using linear regression and Bland-Altman
      analyses. For all assays, precision was moderate but acceptable and dilution
      parallelism was good. All assays showed analytic performance similar to other
      immunoassays used in veterinary medicine. However, the results from the three
      assays were poorly comparable. Our study highlights the need for an optimised
      species-specific assay for equine samples. 

PMID- 24295743
TI  - Life cycle assessment of corn-based ethanol production in Argentina.
AB  - The promotion of biofuels as energy for transportation in the world is mainly
      driven by the perspective of oil depletion, the concerns about energy security
      and global warming. In Argentina, the legislation has imposed the use of biofuels
      in blend with fossil fuels (5 to 10%) in the transport sector. The aim of this
      paper is to assess the environmental impact of corn-based ethanol production in
      the province of Santa Fe in Argentina based on the life cycle assessment
      methodology. The studied system includes from raw materials production to
      anhydrous ethanol production using dry milling technology. The system is divided
      into two subsystems: agricultural system and refinery system. The treatment of
      stillage is considered as well as the use of co-products (distiller's dried
      grains with solubles), but the use and/or application of the produced biofuel is
      not analyzed: a cradle-to-gate analysis is presented. As functional unit, 1MJ of
      anhydrous ethanol at biorefinery is chosen. Two life cycle impact assessment
      methods are selected to perform the study: Eco-indicator 99 and ReCiPe. SimaPro
      is the life cycle assessment software used. The influence of the perspectives on
      the model is analyzed by sensitivity analysis for both methods. The two selected
      methods identify the same relevant processes. The use of fertilizers and
      resources, seeds production, harvesting process, corn drying, and phosphorus
      fertilizers and acetamide-anillide-compounds production are the most relevant
      processes in agricultural system. For refinery system, corn production, supplied
      heat and burned natural gas result in the higher contributions. The use of
      distiller's dried grains with solubles has an important positive environmental
      impact. 

PMID- 24295744
TI  - Geochemistry and mineralogy of arsenic in mine wastes and stream sediments in a
      historic metal mining area in the UK.
AB  - Mining generates large amounts of waste which may contain potentially toxic
      elements (PTE), which, if released into the wider environment, can cause air,
      water and soil pollution long after mining operations have ceased. The fate and
      toxicological impact of PTEs are determined by their partitioning and speciation
      and in this study, the concentrations and mineralogy of arsenic in mine wastes
      and stream sediments in a former metal mining area of the UK are investigated.
      Pseudo-total (aqua-regia extractable) arsenic concentrations in all samples from
      the mining area exceeded background and guideline values by 1-5 orders of
      magnitude, with a maximum concentration in mine wastes of 1.8*10(5)mgkg(-1) As
      and concentrations in stream sediments of up to 2.5*10(4)mgkg(-1) As, raising
      concerns over potential environmental impacts. Mineralogical analysis of the
      wastes and sediments was undertaken by scanning electron microscopy (SEM) and
      automated SEM-EDS based quantitative evaluation (QEMSCAN(r)). The main arsenic
      mineral in the mine waste was scorodite and this was significantly correlated
      with pseudo-total As concentrations and significantly inversely correlated with
      potentially mobile arsenic, as estimated from the sum of exchangeable, reducible
      and oxidisable arsenic fractions obtained from a sequential extraction procedure;
      these findings correspond with the low solubility of scorodite in acidic mine
      wastes. The work presented shows that the study area remains grossly polluted by
      historical mining and processing and illustrates the value of combining
      mineralogical data with acid and sequential extractions to increase our
      understanding of potential environmental threats. 

PMID- 24295746
TI  - Source apportionment of size-segregated atmospheric particles based on the major
      water-soluble components in Lecce (Italy).
AB  - Atmospheric aerosols have potential effects on human health, on the radiation
      balance, on climate, and on visibility. The understanding of these effects
      requires detailed knowledge of aerosol composition and size distributions and of
      how the different sources contribute to particles of different sizes. In this
      work, aerosol samples were collected using a 10-stage Micro-Orifice Uniform
      Deposit Impactor (MOUDI). Measurements were taken between February and October
      2011 in an urban background site near Lecce (Apulia region, southeast of Italy).
      Samples were analysed to evaluate the concentrations of water-soluble ions (SO4(2
      ), NO3(-), NH4(+), Cl(-), Na(+), K(+), Mg(2+) and Ca(2+)) and of water-soluble
      organic and inorganic carbon. The aerosols were characterised by two modes, an
      accumulation mode having a mass median diameter (MMD) of 0.35 +/- 0.02 MUm,
      representing 51 +/- 4% of the aerosols and a coarse mode (MMD=4.5 +/- 0.4 MUm),
      representing 49 +/- 4% of the aerosols. The data were used to estimate the losses
      in the impactor by comparison with a low-volume sampler. The average loss in the
      MOUDI-collected aerosol was 19 +/- 2%, and the largest loss was observed for NO3(
      ) (35 +/- 10%). Significant losses were observed for Ca(2+) (16 +/- 5%), SO4(2-)
      (19 +/- 5%) and K(+) (10 +/- 4%), whereas the losses for Na(+) and Mg(2+) were
      negligible. Size-segregated source apportionment was performed using Positive
      Matrix Factorization (PMF), which was applied separately to the coarse (size
      interval 1-18 MUm) and accumulation (size interval 0.056-1 MUm) modes. The PMF
      model was able to reasonably reconstruct the concentration in each size-range.
      The uncertainties in the source apportionment due to impactor losses were
      evaluated. In the accumulation mode, it was not possible to distinguish the
      traffic contribution from other combustion sources. In the coarse mode, it was
      not possible to efficiently separate nitrate from the contribution of
      crustal/resuspension origin.

PMID- 24295745
TI  - Investigation of carbon dioxide emission in China by primary component analysis.
AB  - Principal component analysis (PCA) is employed to investigate the relationship
      between CO2 emissions (COEs) stemming from fossil fuel burning and cement
      manufacturing and their affecting factors. Eight affecting factors, namely,
      Population (P), Urban Population (UP); the Output Values of Primary Industry
      (PIOV), Secondary Industry (SIOV), and Tertiary Industry (TIOV); and the
      Proportions of Primary Industry's Output Value (PPIOV), Secondary Industry's
      Output Value (PSIOV), and Tertiary Industry's Output Value (PTIOV), are chosen.
      PCA is employed to eliminate the multicollinearity of the affecting factors. Two
      principal components, which can explain 92.86% of the variance of the eight
      affecting factors, are chosen as variables in the regression analysis. Ordinary
      least square regression is used to estimate multiple linear regression models, in
      which COEs and the principal components serve as dependent and independent
      variables, respectively. The results are given in the following. (1)
      Theoretically, the carbon intensities of PIOV, SIOV, and TIOV are 2573.4693,
      552.7036, and 606.0791 kt per one billion $, respectively. The incomplete
      statistical data, the different statistical standards, and the ideology of self
      sufficiency and peasantry appear to show that the carbon intensity of PIOV is
      higher than those of SIOV and TIOV in China. (2) PPIOV, PSIOV, and PTIOV
      influence the fluctuations of COE. The parameters of PPIOV, PSIOV, and PTIOV are 
      2706946.7564, 2557300.5450, and 3924767.9807 kt, respectively. As the economic
      structure of China is strongly tied to technology level, the period when PIOV
      plays the leading position is characterized by lagging technology and economic
      developing. Thus, the influence of PPIOV has a negative value. As the increase of
      PSIOV and PTIOV is always followed by technological innovation and economic
      development, PSIOV and PTIOV have the opposite influence. (3) The carbon
      intensities of P and UP are 1.1029 and 1.7862 kt per thousand people,
      respectively. The carbon intensity of the rural population can be inferred to be
      lower than 1.1029 kt per thousand people. The characteristics of poverty and the
      use of bio-energy in rural areas result in a carbon intensity of the rural
      population that is lower than that of P.

PMID- 24295747
TI  - Toxicity of spill-treating agents and oil to sea urchin embryos.
AB  - The aim of this study was to assess the joint toxicity of a Maya crude oil and
      four spill-treating agents (STAs) (CytoSol, Finasol OSR51, Agma OSD569 and
      OD4000). The acute toxicity of the binary mixtures of the water accommodated
      fractions (WAFs) obtained independently for the oil and each STA was assessed.
      The toxicity of the chemically enhanced WAF (CEWAF) of oil and Finasol OSR51 at
      several dispersant to oil ratios (1:2, 1:10 and 1:100) was also evaluated. The
      toxicity (EC50) obtained for the WAFs of the STAs was: CytoSol (15.1 mL/L)<Agma
      OSD 569 (9.8 mL/L)<OD4000 (2.6 mL/L)<and Finasol OSR 51 (1.8 mL/L). An accurate
      description of the toxicity of binary mixtures was obtained by the following
      models: Concentration Addition (Agma OSD569 and CytoSol), Independent Action
      (Finasol OSR51) and extended Concentration Addition model to describe
      antagonistic effects (OD4000). The CEWAFs showed an intermediate position between
      the more moderate effects of the WAF of oil and the higher toxicity of the WAFs
      of Finasol OSR51, which suggested the high sensitivity of the sea urchin embryo
      toward the dispersant.

PMID- 24295748
TI  - Persistent organic pollutants in soil near the Changwengluozha glacier of the
      Central Tibetan Plateau, China: their sorption to clays and implication.
AB  - Twenty-seven soil samples were collected at ca. 5,000 m from the Changwengluozha
      glacier. In addition to soil components, the concentration of 23 organochlorine
      pesticides (OCPs) and 16 polycyclic aromatic hydrocarbons (PAHs) were analyzed.
      Clay minerals were found to play a key role in the accumulation of OCPs/PAHs in
      soil. The sorption ratio of chemical to clay was ordered in the OCPs and PAHs to
      the vapor pressure in a negatively correlated fashion. Because of the negative
      relationship between vapor pressure and the soil-air partition coefficients
      (KSA), it was understood that the higher sorption ratio responded to a higher
      KSA, which indicated the fate of the contaminants in soil. The soil near the
      Changwengluozha glacier functioned as a "sink" for OCPs in the decreasing order
      of 2,4'-DDT, 4,4'-DDD, HCB, delta-HCH, and alpha-HCH and for PAHs in an
      decreasing order of Pyr, Flu, Fl, Ace, and Acy.

PMID- 24295749
TI  - Separation and measurement of silver nanoparticles and silver ions using magnetic
      particles.
AB  - The recent surge in consumer products and applications using metallic
      nanoparticles has increased the possibility of human or ecosystem exposure due to
      unintentional release into the environment. To protect consumer health and the
      environment, there is an urgent need to develop tools that can characterize and
      quantify these materials at low concentrations and in complex matrices. In this
      study, magnetic nanoparticles coated with either dopamine or glutathione were
      used to develop a new, simple and reliable method for the separation/pre
      concentration of trace amounts of silver nanoparticles followed by their
      quantification using inductively coupled plasma mass spectrometry (ICP-MS). The
      structurally modified magnetic particles were able to capture trace amounts of
      silver nanoparticles (~2 ppb) and concentrate (up to 250 times) the particles for
      analysis with ICP-MS. Under laboratory conditions, recovery of silver
      nanoparticles was >99%. More importantly, the magnetic particles selectively
      captured silver nanoparticles in a mixture containing both nano-particulate and
      ionic silver. This unique feature addresses the challenges of separation and
      quantification of silver nanoparticles in addition to the total silver in
      environmental samples. Spiking experiments showed recoveries higher than 97% for
      tap water and both fresh and saline surface water.

PMID- 24295750
TI  - Divergences on the environmental impact associated to the production of maritime
      pine wood in Europe: French and Portuguese case studies.
AB  - Life Cycle Assessment (LCA) has become a common methodology to evaluate the
      environmental performance of forest systems in recent years. This study aims to
      estimate the environmental profile associated with maritime pine wood production
      in two representative European countries: Portugal and France. Different forest
      management regimes based on low and high intensive conditions were evaluated and
      differences in logging equipment, biomass yield and lifespan were also reported.
      The study was completed with a sensitivity analysis based on two allocation
      approaches (economic and volumetric) since biomass from thinning processes is
      harvested and can be used as a co-product. The production of maritime pine in
      Portugal under low intensity conditions should present the best environmental
      results with reductions of 50-94% in comparison with the worst scenario. It is
      mainly associated with the absence of forest activities in periods previous to
      the logging stage. French intensive forest scenario ranks as the second best
      alternative of pine wood production. The remaining scenarios reported worse
      results in terms of environmental impacts mostly due to the remarkable repetition
      of a selection of those forest activities with large fuel requirement (mainly on
      site preparation and stand establishment and tending). Regardless of the
      scenario, logging related activities such as final cutting and forwarding were
      identified as the hotspots mainly due to the fuel requirements. Fertilizer
      production (if required), thinning and cleaning processes reported also
      remarkable contributions to the categories under assessment. In addition, an
      economic estimation for each forest management scenario has been performed mainly
      considering fuel, machinery and labor costs. According to the results, the
      Portuguese low intensive scenario is the best choice together with the French
      intensive scenario under an economic point of view because of the lowest
      production costs per functional unit. Activities related with the logging stage
      have also been identified as economic hotspots. 

PMID- 24295751
TI  - Associations of neonatal lead, cadmium, chromium and nickel co-exposure with DNA
      oxidative damage in an electronic waste recycling town.
AB  - OBJECTIVE: This study aimed to evaluate the effects of toxic heavy metal co
      exposure on DNA oxidative damage in neonates from a primitive e-waste recycling
      region, Guiyu town, China. METHODS: Our participants included 201 pregnant women:
      126 from Guiyu town and 75 from Jinping district of Shantou city, where no e
      waste recycling and dismantling activities existed. Structured interview
      questionnaires were administered to the pregnant women and umbilical cord blood
      (UCB) samples were collected after delivery. The UCB concentrations of lead,
      cadmium, chromium, and nickel were analyzed by graphite furnace atomic absorption
      spectrometry (GFAAS). Levels of UCB plasma 8-hydroxydeoxyguanosine (8-OHdG, a DNA
      oxidative damage biomarker) were determined by enzyme-linked immunosorbent assay.
      RESULTS: Our results suggested that UCB lead and cadmium concentrations in
      neonates of Guiyu were significantly higher than those of Jinping (lead: median
      110.45 ng/mL vs. 57.31 ng/mL; cadmium: median 2.50 ng/mL vs. 0.33 ng/mL, both
      P<0.001). Parents' residence in Guiyu, and parents' work related to e-waste
      recycling were the risk factors associated with neonate's UCB lead and cadmium
      levels. No significant difference of UCB plasma 8-OHdG levels was found between
      Guiyu and the control area. After adjusting for potential confounders, cord
      plasma 8-OHdG concentrations (ng/mL) were positively associated with blood
      cadmium (beta=0.126 ng/mL, 95% CI: 0.055 to 0.198 ng/mL), chromium (beta=0.086
      ng/mL, 95% CI: 0.014 to 0.158 ng/mL) and nickel (beta=0.215 ng/mL, 95% CI: 0.113
      to 0.317 ng/mL) concentrations. CONCLUSIONS: The primitive e-waste recycling and
      dismantling activities may contribute to the elevated umbilical cord blood toxic
      heavy metal levels in neonates born in Guiyu. Exposures to cadmium, chromium and
      nickel were associated with increased oxidative DNA damage in neonates.

PMID- 24295752
TI  - Water quality assessment of an unusual ritual well in Bangladesh and impact of
      mass bathing on this quality.
AB  - A sacred ritual well with continuously discharging of methane gas through its
      water body was studied for physicochemical and microbiological quality in three
      seasons and during ritual mass bathing. Most of the physicochemical parameters
      showed significant seasonal variations (P<0.05) and a sharp fluctuation during
      mass bathing. Dissolved oxygen (DO) was found negatively correlated with
      temperature (r=-0.384, P<0.05), biochemical oxygen demand (BOD) (r=-0.58,
      P<0.001) and ammonia (r=-0.738, P<0.001), while BOD showed positive correlation
      with chemical oxygen demand (COD) (r=0.762, P<0.001) and ammonia (r=0.83,
      P<0.001). Simple regression analysis also yielded significant linear relationship
      in DO vs. temperature (r(2)=0.147, P<0.05), DO vs. ammonia (r(2)=0.544, P<0.001)
      and BOD vs. DO (r(2)=0.336, P<0.001). A total of eight microbial indicators were
      studied and found that all of them increased unusually during mass bathing
      comparing with their respective seasonal values. Total coliforms (TC) were found
      positively correlated with fecal coliforms (FC) (r=0.971), FC with Escherichia
      coli (EC) (r=0.952), EC with intestinal enterococci (IE) (r=0.921), fecal
      streptococci (FS) with IE (r=0.953) and Staphylococcus aureus (SA) with
      Pseudomonas aeruginosa (PA) (r=0.946), which were significant at P<0.001. Some
      regression models showed significant linear relationship at P<0.001 with r(2)
      value of 0.943 for FC vs. TC, 0.907 for EC vs. FC, 0.869 for FS vs. FC, 0.848 for
      IE vs. EC and 0.909 for IE vs. FS. The overall results found in this study
      revealed that well water is suitable for bathing purpose but the religious
      activity considerably worsen its quality. 

PMID- 24295753
TI  - Temporal evolution of depth-stratified groundwater salinity in municipal wells in
      the major aquifers in Texas, USA.
AB  - We assessed spatial distribution of total dissolved solids (TDS) in shallow (<50
      m), intermediate (50-150 m), and deep (>150 m) municipal (domestic and public
      supply) wells in nine major aquifers in Texas for the 1960s-1970s and 1990s-2000s
      periods using geochemical data obtained from the Texas Water Development Board.
      For both time periods, the highest median groundwater TDS concentrations in
      shallow wells were found in the Ogallala and Pecos Valley aquifers and that in
      the deep wells were found in the Trinity aquifer. In the Ogallala, Pecos Valley,
      Seymour and Gulf Coast aquifers, >60% of observations from shallow wells exceeded
      the secondary maximum contaminant level (SMCL) for TDS (500 mg L(-1)) in both
      time periods. In the Trinity aquifer, 72% of deep water quality observations
      exceeded the SMCL in the 1990s-2000s as compared to 64% observations in the 1960s
      1970s. In the Ogallala, Edwards-Trinity (plateau), and Edwards (Balcones Fault
      Zone) aquifers, extent of salinization decreased significantly (p<0.05) with well
      depth, indicating surficial salinity sources. Geochemical ratios revealed strong
      adverse effects of chloride (Cl(-)) and sulfate (SO4(2-)) on groundwater
      salinization throughout the state. Persistent salinity hotspots were identified
      in west (southern Ogallala, north-west Edwards-Trinity (plateau) and Pecos Valley
      aquifers), north central (Trinity-downdip aquifer) and south (southern Gulf Coast
      aquifer) Texas. In west Texas, mixed cation SO4-Cl facies led to groundwater
      salinization, as compared to Na-Cl facies in the southern Gulf Coast, and Ca-Na
      HCO3 and Na-HCO3 facies transitioning to Na-Cl facies in the Trinity-downdip
      regions. Groundwater mixing ensuing from cross-formational flow, seepage from
      saline plumes and playas, evaporative enrichment, and irrigation return flow had
      led to progressive groundwater salinization in west Texas, as compared to ion
      exchange processes in the north-central Texas, and seawater intrusion coupled
      with salt dissolution and irrigation return flow in the southern Gulf Coast
      regions.

PMID- 24295754
TI  - Comparison of greenhouse gas emissions from rice paddy fields under different
      nitrogen fertilization loads in Chongming Island, Eastern China.
AB  - Rice is one of the major crops of southern China and Southeast Asia. Rice paddies
      are one of the largest agricultural greenhouse gas (GHG) sources in this region
      because of the application of large quantities of nitrogen (N) fertilizers to the
      plants. In particular, the production of methane (CH4) is a concern.
      Investigating a reasonable amount of fertilizers to apply to plants is essential
      to maintaining high yields while reducing GHG emissions. In this study, three
      levels of fertilizer application [high (300 kg N/ha), moderate (210 kg N/ha), and
      low (150 kg N/ha)] were designed to examine the effects of variation in N
      fertilizer application rate on carbon dioxide (CO2), methane (CH4), and nitrous
      oxide (N2O) emissions from the paddy fields in Chongming Island, Shanghai, China.
      The high level (300 kg N/ha) represented the typical practice adopted by the
      local farmers in the area. Maximum amounts of CH4 and N2O fluxes were observed
      upon high-level fertilizer application in the plots. Cumulative N2O emissions of
      23.09, 40.10, and 71.08 mg N2O/m(2) were observed over the growing season in 2011
      under the low-, moderate-, and high-level applications plots, respectively. The
      field data also indicated that soil temperatures at 5 and 10 cm soil depths
      significantly affected soil respiration; the relationship between Rs and soil
      temperature in this study could be described by an exponential model. Our study
      showed that reducing the high rate of fertilizer application is a feasible way of
      attenuating the global-warming potential while maintaining the optimum yield for
      the studied paddy fields.

PMID- 24295755
TI  - Occurrence and bioaccumulation of pharmaceuticals in a fish species inhabiting
      the Suquia River basin (Cordoba, Argentina).
AB  - In South America, there is a lack of data concerning the occurrence and levels of
      pharmaceuticals in main rivers as well as their negative effects on the biota.
      Here we report the occurrence as well as the spatial and temporal variations of
      some common prescribed pharmaceuticals in the Suquia River basin (Cordoba,
      Argentina). We also report the bioconcentration of two of them in Gambusia
      affinis, a widely distributed fish species inhabiting the river basin. The
      influence of the wastewater treatment plant of Cordoba City was critical (up to
      70 km downstream). Among 15 compounds analyzed, atenolol, carbamazepine and
      diclofenac were the most frequently detected (reaching sub MUg L(-1) levels),
      showing different distribution patterns. Bioconcentration of atenolol and
      carbamazepine was studied under laboratory controlled conditions. Estimated
      bioconcentration factors (BCFs) were: 0.13 and 0.08 L kg(-1) upon exposure to 100
      and 1,000 MUg L(-1) atenolol in water, respectively; while BCFs were 0.7 and 0.9
      L kg(-1) when exposed to 10 and 100 MUg L(-1) carbamazepine, respectively. To the
      extent of our knowledge, this is the first report on pharmaceuticals in
      superficial waters of Argentina as well as the first report on the
      bioaccumulation of atenolol in whole body fish.

PMID- 24295756
TI  - Determining the contributions of urbanisation and climate change to NPP
      variations over the last decade in the Yangtze River Delta, China.
AB  - Terrestrial net primary production (NPP) is an important measure of global
      change, and identifying the relative contributions of urbanisation and climate
      change to NPP is important for understanding the impact of human and natural
      influences on terrestrial systems and the carbon cycle. The objective of this
      study was to reveal how urbanisation and climate drive changes in NPP. Satellite
      based estimates of NPP collected over a 12-year period (1999-2010) were analysed
      to identify NPP variations in the Yangtze River Delta. Temporal and spatial
      analysis methods were used to identify the relationships among NPP, nighttime
      light urbanisation index values, and climatic factors from pixel to regional
      scales. The NPP of the entire Yangtze River Delta decreased slightly at a rate of
      -0.5 g C m(-2)a(-1) from 1999 to 2010, but this change was not significant.
      However, in the urban region, NPP decreased significantly (p<0.05) at a rate of 
      4.7 g C m(-2)a(-1) due to urbanisation processes. A spatially explicit method was
      proposed to partition the relative contributions of urbanisation and climate
      change to NPP variation. The results revealed that the urbanisation factor is the
      main driving force for NPP change in high-speed urbanisation areas, and the
      factor accounted for 47% of the variations. However, in the forest and farm
      regions, the NPP variation was mainly controlled by climate change and residual
      factors.

PMID- 24295757
TI  - The identification of 'hotspots' of heavy metal pollution in soil-rice systems at
      a regional scale in eastern China.
AB  - Chinese agricultural soils and crops are suffering from increasing damage from
      heavy metals, which are introduced from various pollution sources including
      agriculture, traffic, mining and especially the flourishing private metal
      recycling industry. In this study, 219 pairs of rice grain and corresponding soil
      samples were collected from Wenling in Zhejiang Province to identify the spatial
      relationship and pollution hotspots of Cd, Cu, Ni and Zn in the soil-rice system.
      The mean soil concentrations of heavy metals were 0.316 mg kg(-1) for Cd, 47.3 mg
      kg(-1) for Cu, 31.7 mg kg(-1) for Ni and 131 mg kg(-1) for Zn, and the metal
      concentrations in rice grain were 0.132 mg kg(-1) for Cd, 2.46 mg kg(-1) for Cu,
      0.223 mg kg(-1) for Ni and 17.4 mg kg(-1) for Zn. The coefficient of variability
      (CV) of soil Cd, Cu and rice Cd were 147%, 146% and 180%, respectively,
      indicating an extensive variability. While the CVs of other metals ranged from
      23.4% to 84.3% with a moderate variability. Kriging interpolation procedure and
      the Local Moran's I index detected the locations of pollution hotspots of these
      four metals. Cd and Cu had a very similar spatial pattern, with contamination
      hotspots located simultaneously in the northwestern part of the study area, and
      there were obvious hotspots for soil Zn in the north area, while in the northeast
      for soil Ni. The existence of hotspots may be due to industrialization and other
      anthropogenic activities. An Enrichment Index (EI) was employed to measure the
      uptake of heavy metals by rice. The results indicated that the accumulation and
      availability of heavy metals in the soil-rice system may be influenced by both
      soil heavy metal concentrations and soil physico-chemical properties. Cross
      correlograms quantitatively illustrated that EIs were significantly correlated
      with soil properties. Soil pH and organic matter were the most important factors
      controlling the uptake of heavy metals by rice. As results, positive measures
      should be taken into account to control soil pollution and to curtail metal
      contamination to the food chain in the areas of Wenling, which were the most
      polluted by toxic metals.

PMID- 24295758
TI  - Exposure to radionuclides in smoke from vegetation fires.
AB  - Naturally occurring radionuclides of uranium, thorium, radium, lead and polonium
      were determined in bushes and trees and in the smoke from summer forest fires.
      Activity concentrations of radionuclides in smoke particles were much enriched
      when compared to original vegetation. Polonium-210 ((210)Po) in smoke was
      measured in concentrations much higher than all other radionuclides, reaching
      7,255 +/- 285 Bq kg(-1), mostly associated with the smaller size smoke particles
      (<1.0 MUm). Depending on smoke particle concentration, (210)Po in surface air
      near forest fires displayed volume concentrations up to 70 m Bq m(-3), while in
      smoke-free air (210)Po concentration was about 30 MU Bq m(-3). The estimated
      absorbed radiation dose to an adult member of the public or a firefighter exposed
      for 24h to inhalation of smoke near forest fires could exceed 5 MUSv per day,
      i.e, more than 2000 times above the radiation dose from background radioactivity
      in surface air, and also higher than the radiation dose from (210)Po inhalation
      in a chronic cigarette smoker. It is concluded that prolonged exposure to smoke
      allows for enhanced inhalation of radionuclides associated with smoke particles.
      Due to high radiotoxicity of alpha emitting radionuclides, and in particular of
      (210)Po, the protection of respiratory tract of fire fighters is strongly
      recommended.

PMID- 24295759
TI  - Impact of historical mining assessed in soils by kinetic extraction and lead
      isotopic ratios.
AB  - The aim of this study is to estimate the long-term behaviour of trace metals, in
      two soils differently impacted by past mining. Topsoils from two 1 km(2) zones in
      the forested Morvan massif (France) were sampled to assess the spatial
      distribution of Cd, Cu, Pb and Zn. The first zone had been contaminated by
      historical mining. As expected, it exhibits higher trace-metal levels and greater
      spatial heterogeneity than the second non-contaminated zone, supposed to
      represent the local background. One soil profile from each zone was investigated
      in detail to estimate metal behaviour, and hence, bioavailability. Kinetic
      extractions were performed using EDTA on three samples: the A horizon from both
      soil profiles and the B horizon from the contaminated soil. For all three
      samples, kinetic extractions can be modelled by two first-order reactions.
      Similar kinetic behaviour was observed for all metals, but more metal was
      extracted from the contaminated A horizon than from the B horizon. More
      surprising is the general predominance of the residual fraction over the "labile"
      and "less labile" pools. Past anthropogenic inputs may have percolated over time
      through the soil profiles because of acidic pH conditions. Stable organo-metallic
      complexes may also have been formed over time, reducing metal availability. These
      processes are not mutually exclusive. After kinetic extraction, the lead isotopic
      compositions of the samples exhibited different signatures, related to
      contamination history and intrinsic soil parameters. However, no variation in
      lead signature was observed during the extraction experiment, demonstrating that
      the "labile" and "less labile" lead pools do not differ in terms of origin. Even
      if trace metals resulting from past mining and metallurgy persist in soils long
      after these activities have ceased, kinetic extractions suggest that metals, at
      least for these particular forest soils, do not represent a threat for biota.

PMID- 24295760
TI  - Greening, new frontiers for research and employment in the agro-food sector.
AB  - The "greening" of the European Union's (EU) Common Agricultural Policy (CAP) is
      meant to protect and enhance biodiversity as well as to make food production more
      sustainable by encouraging, for example, the responsible use of natural
      resources. The "greening" process seems to be driven by, first of all, the policy
      push through various policy and regulatory measures. Farmers have to invest time
      and resources in maintaining permanent grasslands, practice crop diversification
      and manage ecological focus areas for which they will receive compensation from
      the EU. "Greening" is also driven by the consumer or market pull generated by
      preferences for more sustainably produced food and sustainability initiatives
      along the agro-food chain. EU investments in research and development activities
      are required for the successful implementation of greening practices.
      Professionals from different disciplines are called upon to provide, in the next
      few years, solutions for all the new requirements in order to realize a
      sustainable and socially and economically healthy agricultural system. Besides
      this, farmers need support to implement and manage greening measures, but also to
      reap the benefits of their investments by networking and engaging with
      stakeholders higher in the agro-food chain, such as retailers and supermarkets.
      This is not only to assure sustainability at processing, packaging and storage,
      but also to increase visibility of farmers' practices to consumers through
      communication that may help influencing consumers' choices. These factors are
      currently not given the importance they need by the EU, but are crucial for a
      successful "greening". 

PMID- 24295761
TI  - MTHFR 1298A>C is a risk factor for autism spectrum disorder in the Korean
      population.

PMID- 24295762
TI  - Attachment insecurities, maladaptive perfectionism, and eating disorder symptoms:
      a latent mediated and moderated structural equation modeling analysis across
      diagnostic groups.
AB  - Although 96-100% of individuals with eating disorders (EDs) report insecure
      attachment, the specific mechanisms by which adult insecure attachment dimensions
      affect ED symptomatology remain to date largely unknown. This study examined
      maladaptive perfectionism as both a mediator and a moderator of the relationship
      between insecure attachment (anxiety and avoidance) and ED symptomatology in a
      clinical, treatment seeking, sample. Insecure anxious and avoidant attachment,
      maladaptive perfectionism, and ED symptomatology were assessed in 403
      participants from three medium size specialized care centres for EDs in Italy.
      Structural equation modeling indicated that maladaptive perfectionism served as
      mediator between both insecure attachment patterns and ED symptomatology. It also
      interacted with insecure attachment to predict higher levels of ED symptoms -
      highlighting the importance of both insecure attachment patterns and maladaptive
      aspects of perfectionism as treatment targets. Multiple-group comparison analysis
      did not reveal differences across diagnostic groups (AN, BN, EDNOS) in mediating,
      main and interaction effects of perfectionism. These findings are consistent with
      recent discussions on the classification and treatment of EDs that have
      highlighted similarities between ED diagnostic groups and could be viewed through
      the lens of the Trans-theoretical Model of EDs. Implications for future research
      and intervention are discussed. 

PMID- 24295763
TI  - Associations between perceived neighbourhood environmental attributes and self
      reported sitting time in patients with schizophrenia: a pilot study.
AB  - Sitting behaviours may, independent of physical activity behaviours, be a
      distinct risk factor for multiple adverse health outcomes in patients with
      schizophrenia. In order to combat sitting behaviours health care providers and
      policy makers require further understanding of its determinants in this
      population group. The aim of the present study was to investigate the variance in
      sitting time explained by a wide range of community design and recreational
      environmental variables, above and beyond the variance accounted for by
      demographic variables. One hundred and twenty-three patients (42?) with
      schizophrenia (mean age=41.5 +/- 12.6 years) were included in the final analysis.
      The built environment was rated using the Instruments for Assessing Levels of
      Physical Activity and Fitness environmental questionnaire and sitting time was
      assessed using the International Physical Activity Questionnaire-short (IPAQ)
      version. Regression analysis showed that environmental variables were related to
      sitting time. The body mass index (BMI) and disease stage explained 8.4% of the
      variance in sitting, while environmental correlates explained an additional
      16.8%. Clinical practice guidelines should incorporate strategies targeting
      changes in sitting behaviours, from encouraging environmental changes to the
      availability of exercise equipment.

PMID- 24295764
TI  - Immobilization of radioactive iodine in silver aluminophosphate glasses.
AB  - Silver aluminophosphate glasses have been investigated as matrices for the
      immobilization of radioactive iodine. In this study, up to 28mol% AgI have been
      incorporated without volatilization thanks to a low temperature synthesis
      protocol. Alumina was added in the composition in order to increase the glass
      transition temperature for a better thermal stability in a repository conditions.
      Two series of glasses have been investigated, based on AgPO3 and Ag5P3O10
      compositions, and with 0-5mol% Al2O3. We report (31)P, (27)Al and (109)Ag NMR
      study of these glasses, including advanced measurement of the connectivities
      through {(27)Al}-(31)P cross-polarization and (31)P-(31)P double-quantum
      correlation. We confirm that AgI is inserted in the aluminophosphate glasses and
      does not form clusters. AgI does not induce any modification of the glass
      polymerization but only an expansion of the network. Despite no evidence for
      crystallization could be obtained from XRD, NMR revealed that the introduction of
      AgI induces an exclusion of alumina from the network, leading to the
      crystallization of aluminophosphate phases such as Al(PO3)3 or AlPO4. As a
      consequence, despite NMR gives evidence for the presence of aluminophosphate
      bonds, only a limited effect of alumina addition on thermal properties is
      observed. 

PMID- 24295765
TI  - Water treatment residues as accumulators of oxoanions in soil. Sorption of
      arsenate and phosphate anions from an aqueous solution.
AB  - Here we report a survey addressed to determine, at different pH values (pH 4.0,
      7.0 and 9.0), the ability of two different water treatment residues, a Fe-based
      (Fe-WTR) and an Al-based (Al-WTR), to accumulate arsenate and phosphate anions
      from an aqueous solution and to define the mechanism which regulate the sorption
      of these anions. Fe-WTR showed a greater As(V) and P(V) sorption capacity respect
      to Al-WTR at all the pH values investigated, in particular at pH 4.0. The greater
      capacity of the Fe-WTR to accumulate phosphate at pH 4.0 seems to be linked to
      the higher content of manganese ions compared to Al-WTR, which can give rise,
      with phosphate ions, to the formation of MnHPO4 precipitates. Sequential
      extraction of As(V)- or P(V)-WTRs suggested that the main mechanism governing the
      sorption of both two anions likely involve the formation of inner-sphere surface
      complexes [Fe/Al-O-As(P)]. Such a coordination mode was supported by the FT-IR
      spectra that exhibit well resolved band at 865cm(-1) and 1040cm(-1) attributable
      to nu(As-O) or nu(P-O) stretching vibration, respectively. 

PMID- 24295766
TI  - Fabrication of glycine-functionalized maghemite nanoparticles for magnetic
      removal of copper from wastewater.
AB  - Maghemite nanoparticles (MNPs) were functionalized with glycine, by a cost
      effective and environmentally friendly procedure, as an alternative route to
      typical amine-functionalized polymeric coatings, for highly efficient removal of
      copper ions from water. MNPs were synthesized by co-precipitation method and
      adsorption of glycine was investigated as a function of ligand concentration and
      pH. The efficiency of these functionalized nanoparticles for removal of Cu(2+)
      from water has been explored and showed that adsorption is highly dependent of pH
      and that it occurs either by forming chelate complexes and/or by electrostatic
      interaction. The adsorption process, which reaches equilibrium in few minutes and
      fits a pseudo second-order model, follows the Langmuir adsorption model with a
      very high maximum adsorption capacity for Cu(2+) of 625mg/g. Furthermore, these
      nanoadsorbents can be used as highly efficient separable and reusable materials
      for removal of toxic metal ions. 

PMID- 24295767
TI  - Influence of natural organic matter on transport and retention of polymer coated
      silver nanoparticles in porous media.
AB  - Interactions between organic matter (OM) and engineered polymer coatings as they
      affect the retention of polyvinylpyrrolidone (PVP) polymer-coated silver
      nanoparticles (AgNPs) were studied. Two distinct types of OM-cysteine
      representing low molecular weight multivalent functional groups, and Suwannee
      River Humic Acid (HA) representing high molecular weight polymers, were
      investigated with respect to their effects on particle stability in aggregation
      and deposition. Aggregation of the PVP coated AgNPs (PVP-AgNPs) was enhanced by
      cysteine addition at high ionic strengths, which was attributed to cysteine
      binding to the AgNPs and replacing the otherwise steric stabilizing agent PVP. In
      contrast the addition of HA did not increase aggregation rates and decreased PVP
      AgNP deposition to the silica porous medium, consistent with enhanced
      electrosteric stabilization by the HA. Although cysteine also reduced deposition
      in the porous medium, the mechanisms of reduced deposition appear to be enhanced
      electric double layer (EDL) interaction at low ionic strengths. At higher ionic
      strengths, aggregation was favored leading to lower deposition due to smaller
      diffusion coefficients and single collector efficiencies despite the reduced EDL
      interactions. 

PMID- 24295768
TI  - Evaluation of the potential of soil remediation by direct multi-channel pulsed
      corona discharge in soil.
AB  - A novel approach, named multi-channel pulsed corona discharge in soil, was
      developed for remediating organic pollutants contaminated soil, with p
      nitrophenol (PNP) as the model pollutant. The feasibility of PNP degradation in
      soil was explored by evaluating effects of pulse discharge voltage, air flow rate
      and soil moisture on PNP degradation. Based on roles of chemically active species
      and evolution of degradation intermediates, PNP degradation processes were
      discussed. Experimental results showed that about 89.4% of PNP was smoothly
      degraded within 60min of discharge treatment at pulse discharge voltage 27kV,
      soil moisture 5% and air flow rate 0.8Lmin(-1), and the degradation process
      fitted the first-order kinetic model. Increasing pulse discharge voltage was
      found to be favorable for PNP degradation, but not for energy yield. There
      existed appropriate air flow rate and soil moisture for obtaining gratifying PNP
      degradation efficacy. Roles of radical scavenger and measurement of active
      species suggested that ozone, H2O2, and OH radicals played very important roles
      in PNP degradation. CN bond in PNP molecule was cleaved, and the main
      intermediate products such as hydroquinone, benzoquinone, catechol, phenol,
      acetic acid, formic acid, oxalic acid, NO2(-) and NO3(-) were identified.
      Possible pathway of PNP degradation in soil in such a system was proposed. 

PMID- 24295769
TI  - Adsorption characteristics of Cu and Zn onto various size fractions of aggregates
      from red paddy soil.
AB  - Soil aggregate is the basic structure unit of soils and the ability of various
      size fractions are different in the aspect of adsorbing and transferring heavy
      metals in the environment. In this study, bulk soil from red paddy field was
      partitioned into four aggregate-size fractions and their adsorption
      characteristics for Cu and Zn were studied. Our results showed that: Pseudo
      second order model was more successful to fit the adsorption process in the
      kinetic experiments and the isothermal experiments data can be described well
      with the Freundlich model as a whole. Due to higher contents in organic matter,
      CEC and free iron oxide, the <0.002mm fraction was found to have the highest
      initial sorption rate and maximum adsorption capacity. The adsorption amount of
      metals increased as the increasing of pH and the percentage of adsorbed metal
      susceptible to desorption into 0.01M NaNO3 was greater for Zn than for Cu, while
      their variation trends were quite opposite. More specific adsorption sites in the
      <0.002mm fraction lead to more desorption amount for this particle size of soil
      at low pH condition. After 60 days of incubation, Cu and Zn were observed to
      enrich in the clay-size aggregates with fractions more stable than other
      particles. 

PMID- 24295770
TI  - Use of DGT and conventional methods to predict sediment metal bioavailability to
      a field inhabitant freshwater snail (Bellamya aeruginosa) from Chinese eutrophic
      lakes.
AB  - In this study, we used the diffusive gradients in thin films (DGT) and
      conventional methods (including SEM-AVS models, BCR sequential extraction and
      total metal concentrations) to assess sediment Cr, Ni, Cu, Zn, Cd and Pb
      bioavailability to field inhabitant freshwater snails (Bellamya aeruginosa) from
      Chinese eutrophic lakes. The performance of these methods and the relationship
      between DGT measurements and conventional methods were evaluated. The results
      showed that DGT-measured metal concentrations have weak correlations with results
      from tests using SEM-AVS models as well as sequentially extracted European
      Community Bureau of Reference (BCR) metal fractions. Among the methods used, Cr,
      Ni, Cu, and Pb measured by DGT were significantly correlated with metal
      concentrations in the tissue of snails, while SEM-AVS could predict Cr, Ni and Pb
      bioavailability well, but not SEM-AVS/fOC. Finally, BCR sequential extraction and
      total metal concentrations only correlated well with Pb bioavailability to
      snails. Overall, the results of this study indicated that DGT performed best in
      predicting metal accumulation in snails and which could be used to predict
      sediment metal bioavailability to field inhabitant snails from freshwater lake
      sediments due to their simple manipulation and validity. 

PMID- 24295771
TI  - Magnetically separable core-shell structural gamma-Fe2O3@Cu/Al-MCM-41
      nanocomposite and its performance in heterogeneous Fenton catalysis.
AB  - To target the low catalytic activity and the inconvenient separation of copper
      loading nanocatalysts in heterogeneous Fenton-like reaction, a core-shell
      structural magnetically separable catalyst, with gamma-Fe2O3 nanoparticles as the
      core layer and the copper and aluminum containing MCM-41 as the shell layer, has
      been fabricated. The role of aluminum has been discussed by comparing the copper
      containing mesoporous silica with various Cu contents. Their physiochemical
      properties have been characterized by XRD, UV-vis, FT-IR, TEM, nitrogen
      physisorption and magnetite susceptibility measurements. Double content Cu
      incorporation results in an improved catalytic activity for phenol degradation at
      the given condition (40 degrees C, initial pH=4), but leads to a declined BET
      surface area and less ordered mesophase structure. Aluminum incorporation helps
      to retain the high BET surface area (785.2m(2)/g) and the regular hexagonal
      mesoporous structure of MCM-41, which make the catalyst possess a lower copper
      content and even a higher catalytic activity than that with the double copper
      content in the absence of aluminum. The catalysts can be facilely separated by an
      external magnetic field for recycle usage. 

PMID- 24295772
TI  - Bioleaching of metals from printed circuit boards supported with surfactant
      producing bacteria.
AB  - This study has evaluated the possibility of bioleaching zinc, copper, lead,
      nickel, cadmium and chromium from printed circuit boards by applying a culture of
      sulphur-oxidising bacteria and a mixed culture of biosurfactant-producing
      bacteria and sulphur-oxidising bacteria. It was revealed that zinc was removed
      effectively both in a traditional solution acidified by a way of microbial
      oxidation of sulphur and when using a microbial culture containing sulphur
      oxidising and biosurfactant-producing bacteria. The average process efficiency
      was 48% for Zn dissolution. Cadmium removal was similar in both media, with a
      highest metal release of 93%. For nickel and copper, a better effect was obtained
      in the acidic medium, with a process effectiveness of 48.5% and 53%,
      respectively. Chromium was the only metal that was removed more effectively in
      the bioleaching medium containing both sulphur-oxidising and biosurfactant
      producing bacteria. Lead was removed from the printed circuit boards with very
      low effectiveness (below 0.5%). Aerating the culture medium with compressed air
      increased the release of all metals in the medium with sulphur and biosurfactant,
      and of Ni, Cu, Zn and Cr in the acidic medium. Increasing the temperature of the
      medium (to 37 degrees C) had a more significant impact in the acidic environment
      than in the neutral environment. 

PMID- 24295773
TI  - CMPO-calix[4]arenes with spacer containing intramolecular hydrogen bonding:
      effect of local rigidification on solvent extraction toward f-block elements.
AB  - To understand intramolecular hydrogen bonding in effecting liquid-liquid
      extraction behavior of CMPO-calixarenes, three CMPO-modified calix[4]arenes (CMPO
      CA) 5a-5c with hydrogen-bonded spacer were designed and synthesized. The impact
      of spacer rotation that is hindered by introduction of intramolecular hydrogen
      bonding upon extraction of La(3+), Eu(3+), Yb(3+), Th(4+), and UO2(2+) has been
      examined. The results show that 5b and 5c containing only one hydrogen bond with
      a less hindered rotation spacer extract La(3+) more efficiently than 5a
      containing two hydrogen bonds with a more hindered rotation spacer, demonstrating
      the importance of local rigidification of spacer in the design of extractants in
      influencing the coordination environment. The large difference in extractability
      between La(3+) and Yb(3+) (or Eu(3+)) by 5b (or 5c), and the small difference by
      5a, suggests intramolecular hydrogen bonding do exert pronounced influence upon
      selective extraction of light and heavy lanthanides. Log-log plot analysis
      indicates a 1:1, 2:1 and 1:1 stoichiometry (ligand/metal) for the extracted
      complex formed between 5b and La(3+), Th(4+), UO2(2+), respectively.
      Additionally, their corresponding acyclic analogs 7a-7c exhibit negligible
      extraction toward these metal ions. These results reveal the possibility of
      selective extraction via tuning local chelating surroundings of CMPO-CA by aid of
      intramolecular hydrogen bonding. 

PMID- 24295774
TI  - Neurotoxic characteristics of spatial recognition damage of the hippocampus in
      mice following subchronic peroral exposure to TiO2 nanoparticles.
AB  - Due to the increased application of titanium dioxide nanoparticles (TiO2 NPs) in
      various areas, numerous studies have been conducted which have confirmed that
      exposure to TiO2 NPs may result in neurological damage in both mice and rats.
      However, very few studies have focused on the molecular mechanisms of spatial
      recognition injury. In the present study, to understand the possible
      neurobiological responses of the mouse hippocampus following subchronic peroral
      exposure to low level TiO2 NPs, mice were exposed to 2.5, 5, and 10mg/kg body
      weight TiO2 NPs for 90 consecutive days. Hippocampal pathology and neuron
      ultrastructure, and long-term potentiation (LTP) were then evaluated, and the
      hippocampal mRNA-expression of several genes and their proteins involved in
      homeostasis of neuronal synaptic plasticity were investigated using a
      quantitative real-time PCR and ELISA method. We observed that subchronic peroral
      exposure to TiO2 NPs caused severe pathological changes, spatial recognition
      impairment, and resulted in significant LTP reduction and down-regulation of N
      methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B) expression associated
      with the simultaneous inhibition of CaMKIV, cyclic-AMP responsive element binding
      proteins (CREB-1, CREB-2), and FosB/DFosB in mouse hippocampal tissues.
      Therefore, our findings suggest that the application of TiO2 NPs in the various
      areas should be paid more attention. 

PMID- 24295775
TI  - Effects of zero-valent metals together with quartz sand on the mechanochemical
      destruction of dechlorane plus coground in a planetary ball mill.
AB  - Mechanochemical destruction by grinding with additives in high energy ball
      milling has been identified as a good alternative to traditional incineration for
      the disposal of wastes containing halogenated organic pollutants. Despite CaO
      normally used as an additive, recently Fe+SiO2 has been used to replace CaO for a
      faster destruction. In the present study, zero-valent metals (Al, Zn, besides Fe)
      together with SiO2 were investigated for their efficiencies of prompting the
      destruction of dechlorane plus (DP). Aluminum was found of be the best with a
      destruction percentage of nearly 99% for either syn- or anti-DP after 2.5h
      milling. In comparison, only 88/85% and 37/32% of syn-/anti-DP were destroyed
      when using zinc and iron after the same time, respectively. The detected water
      soluble chloride was lower than the stoichiometric amount containing in the
      original DP samples, due to the Si-Cl bond formed during the process. The
      potential fate of C and Cl present in DP is in the form of inorganic carbon,
      inorganic Cl and formation of Si-Cl bonds, respectively. The results suggested
      that Al+SiO2 is promising in the mechanochemical destruction of chlorinated
      organic pollutants like DP. 

PMID- 24295776
TI  - Leaching of hazardous substances from a composite construction product--an
      experimental and modelling approach for fibre-cement sheets.
AB  - The leaching behaviour of a commercial fibre-cement sheet (FCS) product has been
      investigated. A static pH dependency test and a dynamic surface leaching test
      have been performed at lab scale. These tests allowed the development of a
      chemical-transport model capable to predict the release of major and trace
      elements over the entire pH range, in function of time. FCS exhibits a cement
      type leaching behaviour with respect to the mineral species. Potentially
      hazardous species are released in significant quantities when compared to their
      total content. These are mainly heavy metals commonly encountered in cement
      matrixes and boron (probably added as biocide). Organic compounds considered as
      global dissolved carbon are released in significant concentrations, originating
      probably from the partial degradation of the organic fibres. The pesticide
      terbutryn (probably added during the preservative treatment of the organic
      fibres) was systematically identified in the leachates. The simulation of an
      upscaled runoff scenario allowed the evaluation of the cumulative release over
      long periods and the distribution of the released quantities in time, in function
      of the local exposure conditions. After 10 years of exposure the release reaches
      significant fractions of the species' total content - going from 4% for Cu to
      near 100% for B. 

PMID- 24295777
TI  - FTIR spectroscopic studies of lithium tetrafluoroborate in propylene
      carbonate+diethyl carbonate mixtures.
AB  - FTIR (Fourier transformed infrared) spectra have been collected and analyzed for
      solutions of lithium tetrafluoroborate in propylene carbonate (PC), diethyl
      carbonate (DEC), and PC+DEC mixtures. It has been shown that the carbonyl stretch
      bands of PC and DEC, the ring of PC and the ether oxygen stretch bands of DEC are
      all very sensitive to the interaction between Li(+) and the solvent molecules.
      New shoulders appear and the original bands split with the addition of LiBF4,
      indicating that a strong interaction between Li(+) and molecules of PC and DEC
      exists through the oxygen group of C=O and ring of PC and both C=O oxygen and
      ether oxygen atoms of DEC. In addition, no preferential solvation of Li(+) in
      LiBF4/PC+DEC solutions was detected.

PMID- 24295778
TI  - Surface-enhanced Raman spectroscopic analysis of maleic hydrazide adsorbed on
      gold surface.
AB  - In this paper, surface-enhanced Raman scattering (SERS) spectra of maleic
      hydrazide (MH, 6-hydroxy-3(2H)-pyridazinone) were studied by using citrate
      reduced gold colloidal nanoparticles. Comparisons between the prominent SERS
      bands and the precise mode descriptions predicted through density functional
      theory (DFT) simulations at the B3LYP/6-311++g(d,p) level allowed an in-depth
      orientation analysis of the adsorbed species on gold surfaces. And main forms of
      hydrogen bonds in the solid state of MH were also determined to be O-H?O.
      Furthermore, the effects of concentration and pH on the SERS spectra of the
      molecule were discussed. It is found that with the different adsorbate
      concentration, the SERS spectra of MH show significant changes in their features,
      indicating different orientations and adsorption sites of the molecule on the
      gold colloidal surface. The SERS and absorption spectra under different pH
      conditions show that a basic environment leads to the deprotonation of N2 and the
      nearly parallel orientation of the MH molecule on the gold surface. Moreover, the
      enhanced characteristic bands were observed at MH concentrations down to about 1
      ppm with the gold colloids, demonstrating a potential of the technique in the
      analysis of MH residues.

PMID- 24295779
TI  - Omega-3 phospholipids from fish suppress hepatic steatosis by integrated
      inhibition of biosynthetic pathways in dietary obese mice.
AB  - Non-alcoholic fatty liver disease (NAFLD) accompanies obesity and insulin
      resistance. Recent meta-analysis suggested omega-3 polyunsaturated fatty acids
      DHA and EPA to decrease liver fat in NAFLD patients. Antiinflammatory,
      hypolipidemic, and insulin-sensitizing effects ofDHA/EPA depend on their lipid
      form, with marine phospholipids showing better efficacy than fish oils. We
      characterized the mechanisms underlying beneficial effects of DHA/EPA
      phospholipids, alone or combined with an antidiabetic drug, on hepatosteatosis.
      C57BL/6N mice were fed for 7 weeks an obesogenic high-fat diet (cHF) or cHF-based
      interventions: (i) cHF supplemented with phosphatidylcholine-rich concentrate
      from herring (replacing 10% of dietary lipids; PC), (ii) cHF containing
      rosiglitazone (10 mg/kg diet; R), or (iii) PC + R. Metabolic analyses, hepatic
      gene expression and lipidome profiling were performed. Results showed that PC and
      PC + R prevented cHlF-induced weight gain and glucose intolerance, while all
      interventions reduced abdominal fat and plasma triacylglycerols. PC and PC + R
      also lowered hepatic and plasma cholesterol and reduced hepatosteatosis.
      Microarray analysis revealed integrated downregulation of hepatic lipogenic and
      cholesterol biosynthesis pathways by PC, while R-induced lipogenesis was fully
      counteracted in PC + R Gene expression changes in PC and PC + R were associated
      with preferential enrichment of hepatic phosphatidylcholine and
      phosphatidylethanolamine fractions by DHA/EPA. The complex downregulation of
      hepatic lipogenic and cholesterol biosynthesis genes and the antisteatotic
      effects were unique to DHA/EPA-containing phospholipids, since they were absent
      in mice fed soy-derived phosphatidylcholine. Thus, inhibition of lipid and
      cholesterol biosynthesis associated with potent antisteatotic effects in the
      liver in response to DHA/EPA-containing phospholipids support their use in NAFLD
      prevention and treatment.

PMID- 24295780
TI  - Reply-histologic chorioamnionitis and neonatal outcome in preterm infants.

PMID- 24295781
TI  - Oral Ulcers as an Initial Presentation of Juvenile Pemphigus: A Case Report.
AB  - Pemphigus vulgaris (PV) is an autoimmune disease in which the autoantibody,
      immunoglobulin G, is directed against the keratinocytes in the epidermis. The
      classic presentations of PV are flaccid vesicles or bullae over the oral mucosa,
      trunk, groin, and extremities. The age of onset is usually between 40 and 60
      years, and cases of PV in children or adolescent patients are rare. Here, we
      present a 17-year-old boy who had painful oral ulcers for 3 months initially and
      bullae spreading to the whole body in the following days. Paraneoplastic
      pemphigus was another differential diagnosis due to the atypical appearance of
      the skin lesion. However, PV was confirmed by hematoxylin and eosin staining and
      immunofluorescence examination of the skin biopsy specimens. The patient had a
      good response to corticosteroid treatment and the immunosuppressive agent,
      rituximab.

PMID- 24295782
TI  - Renal excretion of water-soluble contrast media after enema in the neonatal
      period.
AB  - BACKGROUND: When abdominal distention occurs or bowel obstruction is suspected in
      the neonatal period, a water-soluble contrast enema is helpful for diagnostic and
      therapeutic purposes. The water-soluble contrast medium is evacuated through the
      anus as well as excreted via the kidneys in some babies. This study was designed
      to evaluate the incidence of renal excretion after enemas using water-soluble
      contrast media and presume the causes. METHODS: Contrast enemas using diluted
      water-soluble contrast media were performed in 23 patients under 2 months of age.
      After the enema, patients were followed with simple abdominal radiographs to
      assess the improvement in bowel distention, and we could also detect the presence
      of renal excretion of contrast media on the radiographs. Reviewing the medical
      records and imaging studies, including enemas and consecutive abdominal
      radiographs, we evaluated the incidence of renal excretion of water-soluble
      contrast media and counted the stay duration of contrast media in urinary tract,
      bladder, and colon. RESULTS: Among 23 patients, 12 patients (52%) experienced the
      renal excretion of water-soluble contrast media. In these patients, stay-in
      bladder durations of contrast media were 1-3 days and stay-in-colon durations of
      contrast media were 1-10 days, while stay-in-colon durations of contrast media
      were 1-3 days in the patients not showing renal excretion of contrast media. The
      Mann-Whitney test for stay-in-colon durations demonstrated the later evacuation
      of contrast media in the patients with renal excretion of contrast media (p =
      0.07). The review of the medical records showed that 19 patients were finally
      diagnosed as intestinal diseases, including Hirschsprung's disease, meconium
      ileum, meconium plug syndrome, and small bowel atresia or stenosis. Fisher's
      exact test between the presence of urinary excretion and intestinal diseases
      indicated a statistically significant difference (p = 0.04). CONCLUSION: The
      intestinal diseases causing bowel obstruction may increase the water-soluble
      contrast media's dwell time in the bowel and also increase urinary excretion.

PMID- 24295783
TI  - Correlations between pulmonary function and childhood asthma control test results
      in 5-11-year-old children with asthma.
AB  - OBJECTIVES: We examined correlations between the two asthma assessment tools,
      pulmonary function tests, and Childhood Asthma Control Test (C-ACT) scores, in 5
      11-year-old children with asthma to determine if the C-ACT scores could predict
      pulmonary function test results. MATERIALS AND METHODS: A total of 172 children
      with asthma aged 5-11 years completed C-ACT questionnaires and underwent
      pulmonary function testing. Correlations between these test results were
      examined. Patients were also placed into two groups, C-ACT scores <=19 and >19,
      to determine if patients with scores >19 had better pulmonary function test
      results. RESULTS: Weak correlations were found between pulmonary function test
      results and childhood asthma control test scores in 5-11-year-old children with
      asthma, with or without the use of an asthma controller. These correlations
      included: 0.061 for FEV1 [confidence interval (CI): -0.022-0.049] and 0.074 for
      MMEF (CI: -0.013-0.037). The proportions of children with C-ACT test scores <=19
      group and those with scores >19 group were not significantly different.
      CONCLUSION: Correlations between C-ACT scores and pulmonary function test results
      were poor for children aged 5-11 years with asthma. FEV1, FVC, FEF25, FEF50,
      FEF75, MMEF, and PEFR were not significantly correlated with C-ACT scores.

PMID- 24295784
TI  - N-acetylglucosaminidase, myeloperoxidase and vascular endothelial growth factor
      serum levels in breast cancer patients.
AB  - Inflammatory cells surround breast carcinomas and may act promoting tumor
      development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has
      been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO)
      is considered a marker for neutrophils activity/accumulation. Vascular
      Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of
      this study was to measure the systemic inflammatory response by measuring serum
      levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate
      this response to the peritumoral inflammatory infiltrate and to prognostic
      factors. Serum samples obtained from women with no evidence of disease (n=31) and
      with breast cancer (n=68) were analyzed for the activities of NAG, MPO and VEGF
      by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy
      volunteers (P<0.0001) and serum levels of MPO were higher in patients with breast
      cancer (P=0.002). Serum levels of NAG were positively correlated to serum levels
      of MPO and VEGF (P<0.0001 and P=0.0012, respectively) and MPO and VEGF serum
      levels had also a positive correlation (P=0.0018). The inflammatory infiltrate
      was not associated to serum levels of the inflammatory markers, and higher levels
      of MPO were associated to lymphovascular invasion negativity (P=0.0175). 

PMID- 24295785
TI  - Discrimination between 5-hydroxymethylcytosine and 5-methylcytosine in DNA by
      selective chemical labeling.
AB  - Detection of DNA damage has been greatly improved following the development of
      equipment and techniques, however, discrimination between 5-hydroxymethylcytosine
      (5-hmC) and 5-methylcytosine (5-mC) is still a thorny problem. In the present
      study, an approach to oxidize and selective label (Ox-Labeling) 5-hmC in native
      DNA has been reported, which conveniently distinguishes 5-hmC from 5-mC using
      simple and effective processes. 

PMID- 24295786
TI  - 1,2,3-Triazole-derived naphthalimides as a novel type of potential antimicrobial
      agents: synthesis, antimicrobial activity, interaction with calf thymus DNA and
      human serum albumin.
AB  - A series of 1,2,3-triazole-derived naphthalimides as a novel type of potential
      antimicrobial agents were synthesized and characterized by IR, NMR and HRMS
      spectra. All the new compounds were screened for their antimicrobial activity
      against four Gram-positive bacteria, four Gram-negative bacteria and three fungi.
      Bioactive assay manifested that 3,4-dichlorobenzyl compound 9e and its
      corresponding hydrochloride 11e showed better anti-Escherichia coli activity than
      Norfloxacin and Chloromycin. Preliminary research revealed that compound 9e could
      effectively intercalate into calf thymus DNA to form compound 9e-DNA complex
      which might block DNA replication and thus exert antimicrobial activities. Human
      serum albumin could effectively store and carry compound 9e by electrostatic
      interaction. 

PMID- 24295787
TI  - Novel di-tertiary-butyl phenylhydrazones as dual cyclooxygenase-2/5-lipoxygenase
      inhibitors: synthesis, COX/LOX inhibition, molecular modeling, and insights into
      their cytotoxicities.
AB  - Although dual inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX)
      enzymes is highly effective than targeting COX or LOX alone, there are only a few
      reports of examining such compounds in case of colorectal cancers (CRC). In the
      present work we report that the novel di-tert-butyl phenol-based dual inhibitors
      DTPSAL, DTPBHZ, DTPINH, and DTPNHZ exhibit significant cytotoxicity against human
      CRC cell lines. Molecular docking studies revealed a good fit of these compounds
      in the COX-2 and 5-LOX protein cavities. The inhibitors show significant
      inhibition of COX-2 and 5-LOX activities and are effective against a panel of
      human colon cancer cell lines including HCA-7, HT-29, SW480 and intestinal
      Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressing
      colon cancer cells, through inhibition of the Hyaluronan/CD44v6 cell survival
      pathway. Western blot analysis and qRT-PCR analyses indicated that the di-tert
      butyl phenol-based dual inhibitors reduce the expression of COX-2, 5-LOX, and
      CD44v6 in human colon cancer HCA-7 cells, while the combination of CD44v6shRNA
      and DTPSAL has an additional inhibitory effect on CD44v6 mRNA expression. The
      synergistic inhibitory effect of Celecoxib and Licofelone on CD44v6 mRNA
      expression suggests that the present dual inhibitors down-regulate cyclooxygenase
      and lipoxygenase enzymes through CD44v6. The compounds also exhibited enhanced
      antiproliferative potency compared to standard dual COX/LOX inhibitor, viz.
      Licofelone. Importantly, the HA/CD44v6 antagonist CD44v6shRNA in combination with
      synthetic compounds had a sensitizing effect on the cancer cells which enhanced
      their antiproliferative potency, a finding which is crucial for the anti
      proliferative potency of the novel synthetic di-tert-butyl phenol based dual COX
      LOX inhibitors in colon cancer cells. 

PMID- 24295788
TI  - A near-infrared fluorescence dye for sensitive detection of hydrogen sulfide in
      serum.
AB  - Cy-Cl, a cationic near-infrared cyanine dye, readily reacts with hydrogen sulfide
      (H2S) via nucleophilic thiolation to give dose-dependent 'turn-off' fluorescence
      and colorimetric read-out, allowing selective detection of low levels of H2S in
      serum and imaging of mitochondrial H2S in living cells. 

PMID- 24295789
TI  - Jack bean alpha-mannosidase: amino acid sequencing and N-glycosylation analysis
      of a valuable glycomics tool.
AB  - Jack bean (Canavalia ensiformis) seeds contain several biologically important
      proteins among which alpha-mannosidase (EC 3.2.1.24) has been purified, its
      biochemical properties studied and widely used in glycan analysis. In the present
      study, we have used the purified enzyme and derived its amino acid sequence
      covering both the known subunits (molecular mass of ~66,000 and ~44,000 Da)
      hitherto not known in its entirety. Peptide de novo sequencing and structural
      elucidation of N-glycopeptides obtained either directly from proteolytic
      digestion or after zwitterionic hydrophilic interaction liquid chromatography
      solid phase extraction-based separation were performed by use of nanoelectrospray
      ionization quadrupole time-of-flight mass spectrometry and low-energy collision
      induced dissociation experiments. De novo sequencing provided new insights into
      the disulfide linkage organization, intersection of subunits and complete N
      glycan structures along with site specificities. The primary sequence suggests
      that the enzyme belongs to glycosyl hydrolase family 38 and the N-glycan sequence
      analysis revealed high-mannose oligosaccharides, which were found to be
      heterogeneous with varying number of hexoses viz, Man8-9GlcNAc2 and
      Glc1Man9GlcNAc2 in an evolutionarily conserved N-glycosylation site. This site
      with two proximal cysteines is present in all the acidic alpha-mannosidases
      reported so far in eukaryotes. Further, a truncated paucimannose type was
      identified to be lacking terminal two mannose, Man1(Xyl)GlcNAc2 (Fuc). 

PMID- 24295790
TI  - Dynamic karyotype, dynamic proteome: buffering the effects of aneuploidy.
AB  - Despite its ubiquity in cancer, link with other pathologies, and role in
      promoting adaptive evolution, the effects of aneuploidy or imbalanced chromosomal
      content on cellular physiology have remained incompletely characterized.
      Significantly, it appears that the detrimental as well as beneficial effects of
      aneuploidy are due to the altered gene expression elicited by the aneuploid
      state. In this review we examine the correlation between chromosome copy number
      changes and gene expression in aneuploid cells. We discuss the primary effects of
      aneuploidy on gene expression and describe the cellular response to altered mRNA
      and protein levels. Moreover, we consider compensatory mechanisms that may
      ameliorate imbalanced gene expression and restore protein homeostasis in
      aneuploid cells. Finally, we propose a novel hypothesis to explain the hitherto
      enigmatic abundance compensation of proteins encoded on supernumerary
      chromosomes. 

PMID- 24295791
TI  - Involvement of heat shock protein 47 in Schistosoma japonicum-induced hepatic
      fibrosis in mice.
AB  - Chronic infection with the blood fluke Schistosoma japonicum is associated with
      both liver cirrhosis and liver cancer. Previously, heat shock protein 47, a
      collagen-specific molecular chaperone, was shown to play a critical role in the
      maturation of procollagen. However, less is known about the role of heat shock
      protein 47 in S. japonicum-induced hepatic fibrosis. We therefore investigated
      the expression of heat shock protein 47 in S. japonicum-induced liver fibrosis
      and attempted to determine whether inhibition of heat shock protein 47 could have
      beneficial effects on fibrosis in vitro and in vivo. In this study, we found that
      the expression of heat shock protein 47 was significantly increased in patients
      with Schistosoma-induced fibrosis, as well as in rodent models.
      Immunohistochemistry revealed heat shock protein 47-positive cells were found in
      the periphery of egg granulomas. Administration of heat shock protein 47-targeted
      short hairpin (sh)RNA remarkably reduced heat shock protein 47 expression and
      collagen deposition in NIH3T3 cells and liver tissue of S. japonicum-infected
      mice. Life-table analysis revealed a dose-dependent prolongation of survival
      rates with the treatment of heat shock protein 47-shRNA in murine fibrosis
      models. Moreover, serum alanine aminotransferase and aspartate transaminase
      activity, splenomegaly, spleen weight index and portal hypertension were also
      measured, which showed improvement with the anti-fibrosis treatment. The fibrosis
      related parameters assessed were expressions of Col1a1, Col3a1, TGF-beta1, CTGF,
      IL-13, IL-17, MMP-9, TIMP-1 and PAI-1 in the liver. This study demonstrated that
      heat shock protein 47-targeted shRNA directly reduced collagen production of
      mouse liver fibrosis associated with S. japonicum. We conclude that heat shock
      protein 47 plays an essential role in S. japonicum-induced hepatic fibrosis in
      mice and may be a potential target for ameliorating the hepatic fibrosis caused
      by this parasite. 

PMID- 24295793
TI  - Health information and communication technology in healthcare communication: the
      good, the bad, and the transformative.

PMID- 24295792
TI  - Visceral disease in castration-resistant prostate cancer.
AB  - Metastatic involvement of the viscera in men with advanced castration-resistant
      prostate cancer (CRPC) has been poorly characterised to date. In 359 CRPC
      patients treated between June 2003 and December 2011, the frequency of
      radiologically detected visceral metastases before death was 32%. Of the 92
      patients with computed tomography performed within 3 mo of death, 49% had
      visceral metastases. Visceral metastases most commonly involved the liver (20%)
      and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo
      (95% confidence interval, 5.9-8.3). Survival was affected by the degree of bone
      involvement at detection of visceral disease, varying from 6.1 mo in men with
      more than six bone metastases to 18.2 mo in men with no bone metastases
      (p=0.001). Heterogeneity was noted in clinical phenotypes and prostate-specific
      antigen trends at development of visceral metastases. Visceral metastases are now
      more commonly detected in men with CRPC, likely due to the introduction of novel
      survival-prolonging treatments. 

PMID- 24295794
TI  - Current education standards are essential for midwives to be capable of
      functioning to their full scope of practice.

PMID- 24295795
TI  - [Neurological disorders after cardiac surgery: Diagnosis of cerebral tumors in
      the postoperative period].
AB  - The incidence of neurologic disorders in the postoperative period of cardiac
      surgery is high and usually due to a combination of pre- and intraoperative
      factors. We present 2 patients with brain tumors diagnosed in the immediate
      postoperative period after sudden onset of neurologic dysfunction. Image studies
      yielded clinically useful information in these 2 cases. 

PMID- 24295796
TI  - Axial rotation mechanics in a cadaveric lumbar spine model: a biomechanical
      analysis.
AB  - BACKGROUND CONTEXT: Postoperative patient motions are difficult to directly
      control. Very slow quasistatic motions are intuitively believed to be safer for
      patients, compared with fast dynamic motions, because the torque on the spine is
      reduced. Therefore, the outcomes of varying axial rotation (AR) angular loading
      rate during in vitro testing could expand the understanding of the dynamic
      behavior and spine response. PURPOSE: To observe the effects of the loading rate
      in AR mechanics of lumbar cadaveric spines via in vitro biomechanical testing.
      STUDY DESIGN: An in vitro biomechanical study in lumbar cadaveric spines.
      METHODS: Fifteen lumbar cadaveric segments (L1-S1) were tested with varying
      loading frequencies of AR. Five different frequencies were normalized with the
      base line frequency (0.125 Hz n=15) in this analysis: 0.05 Hz (n=6), 0.166 Hz
      (n=6), 0.2 Hz (n=10), 0.25 Hz (n=10), and 0.4 Hz (n=8). RESULTS: The lowest
      frequency (0.05 Hz) revealed significant differences (p<.05) for all parameters
      (torque, passive angular velocity, axial velocity [AV], axial reaction force
      [RF], and energy loss [EL]) with respect to all other frequencies. Significant
      differences (p<.05) were observed in the following: torque (0.4 Hz with respect
      to 0.2 Hz and 0.25 Hz), passive sagittal angular velocity (SAV) (0.4 Hz with
      respect to all other frequencies; 0.166 Hz with respect to 0.25 Hz), axial linear
      velocity (0.4 Hz with respect to all other frequencies), and RF (0.4 Hz with
      respect to 0.2 Hz and 0.25 Hz). Strong correlations (R2>0.75, p<.05) were
      observed between RF with intradiscal pressure (IDP) and AR angular displacement
      with IDP. Intradiscal pressure (p<.05) was significantly larger in 0.2 Hz in
      comparison with 0.125 Hz. CONCLUSIONS: Evidences suggest that measurements at
      very small frequencies (0.05 Hz) of torque, SAV, AV, RF, and EL are significantly
      reduced when compared with higher frequencies (0.166 Hz, 0.2 Hz, 0.25 Hz, and 0.4
      Hz). Higher frequencies increase torque, RF, passive SAV, and AV. Higher
      frequencies induce a greater IDP in comparison with lower frequencies.

PMID- 24295797
TI  - Experimental chemonucleolysis with recombinant human matrix metalloproteinase 7
      in human herniated discs and dogs.
AB  - BACKGROUND CONTEXT: Chemonucleolysis has been proposed as a less invasive
      technique than surgery for patients with lumbar disc herniation. Once chymopapain
      had been approved as a chemonucleolysis drug, it was withdrawn because of serious
      complications. A novel agent with fewer complications would be desirable.
      PURPOSE: The purpose of this study was to investigate the effects of recombinant
      human matrix metalloproteinase 7 (rhMMP-7) in experimental chemonucleolysis in
      vitro and in vivo and examine its effects on tissue damage. STUDY DESIGN: The
      study design is the experimental study using human herniated discs and enzyme
      substrates in vitro and dogs in vivo. METHODS: The effects of rhMMP-7 on the
      degradation of human herniated discs were examined by measuring the wet weight in
      vitro. The correlations between the decrease in wet weight by rhMMP-7 and the
      conditions associated with herniated discs were also analyzed. The effects of
      rhMMP-7 on the proteoglycan and water contents were respectively examined with
      alcian blue staining and T2-weighted magnetic resonance imaging at 7 days after
      intradiscal injection in dogs. The distribution of [125I]-labeled rhMMP-7 was
      investigated by autoradioluminography at 7 days after intradiscal injection in
      dogs. An epidural injection study with rhMMP-7 was performed to evaluate the
      effects on the tissue damage around the discs at 1 and 13 weeks after the
      treatment in dogs. The Type 1 and 2 collagen cleavage rates were measured and
      compared with those of aggrecan in vitro. RESULTS: Recombinant human matrix
      metalloproteinase 7 concentration dependently decreased the wet weight of
      herniated discs in vitro. The decrease in wet weight of the discs by rhMMP-7 did
      not significantly correlate with the conditions associated with herniated discs.
      Intradiscal injection of rhMMP-7 reduced the proteoglycan and water contents,
      with an increase in the serum keratan sulfate levels. Radioactivity of [125I]
      labeled rhMMP-7 was detected in the nucleus pulposus and annulus fibrosus but not
      in the muscle. Epidural injection of rhMMP-7 had no effect on the injection site
      or the nerve tissues. The Type 1 and 2 collagen cleavage rates of rhMMP-7 were
      1,000-fold weaker than those of aggrecan. CONCLUSIONS: This study demonstrated
      experimental chemonucleolysis with rhMMP-7 in vitro and in vivo. The effects of
      rhMMP-7 were not affected by the conditions associated with herniated discs. The
      epidural injection study together with the autoradioluminography and in vitro
      enzyme assay suggests that intradiscal injection of rhMMP-7 may not induce tissue
      damage around the discs because of its distribution and substrate selectivity.
      Recombinant human matrix metalloproteinase 7 may be a novel and promising
      chemonucleolysis agent.

PMID- 24295798
TI  - Brace treatment is effective in idiopathic scoliosis over 45 degrees : an
      observational prospective cohort controlled study.
AB  - BACKGROUND CONTEXT: Recently, positive results in bracing patients with
      idiopathic scoliosis (IS) above 45 degrees  who refused surgery have been
      presented in a retrospective study. Obviously, this can give only an efficacy
      (EA) analysis, as there is neither a control group, nor it is possible to know
      failures because of dropouts. PURPOSE: To present the prospective results of
      bracing patients affected by IS above 45 degrees  and still growing. STUDY
      DESIGN: Prospective study including all IS patients with 45 degrees  or more,
      Risser stage 0 to 4, who had their first evaluation in our institute, an
      outpatient clinic specialized in scoliosis evaluation and conservative treatment,
      from March 1, 2003 to December 21, 2010 and utterly denied any surgical
      intervention. PATIENT SAMPLE: Of 59 patients, we excluded 2 patients still in
      treatment and 57 (11 males) patients were included. At the beginning of the
      study, they were 15 years 3+/-22 months of age, had 52.5 degrees  Cobb (range, 45
      degrees -93 degrees ), and Risser 2 (0-4). Thirty-nine accepted a full-time brace
      treatment (BG) to try avoiding surgery, 18 refused any treatment and served as
      controls (CG). OUTCOME MEASURES: Physiological measures: radiographic and
      clinical data. METHODS: Treatment: A year of full-time Sforzesco brace (23
      hours/day) or Risser cast (8-12 months) and gradual weaning after Risser 3; all
      patients performed exercises; and International Society on Scoliosis Orthopaedic
      and Rehabilitation TREATMENT management criteria were respected. Analyses: EA in
      patients who completed treatment/observation (34 in BG and 10 in CG) and intent
      to-treat (ITT) with worst case analysis in the whole population. Relative risk
      (RR) and 95% confidence interval (CI) have been computed. RESULTS: Efficacy:
      failures were 23.5% in BG and 100% in CG. Intent-to-treat: failures were 20.5% in
      BG and 55.6% in CG. Relative risks of failure in CG were 4.3 (95% CI, 3.6-4.9) in
      EA and 2.7 (95% CI, 2.0-3.5) in ITT (p<.05). Percentage of patients (53.8%)
      improved: RRs of improvement in BG were 1.6 (95% CI, 1.46-1.9) in EA and 1.9 (95%
      CI, 1.6-2.2) in ITT (p<.05). Patients who joined the treatment achieved a 10.4
      degrees +/-10.7 degrees  Cobb improvement, an ATR reduction of 4.2 degrees +/-4.3
      degrees , and an esthetic improvement of 2.8+/-1.9 of 12 points (TRACE). At the
      end, in BG, 24 patients were below 45 degrees  and 6 patients below 35 degrees .
      CONCLUSIONS: Through this study we can conclude that the conservative brace plus
      exercises treatment (if correctly performed and managed) is a suitable
      alternative for those patients who reject any surgical intervention for IS above
      45 degrees . But we could also conclude that a good brace treatment should be
      considered as the first choice to try avoiding fusion because of the high
      sanitary and social costs of surgery.

PMID- 24295799
TI  - Height drift correction in non-raster atomic force microscopy.
AB  - We propose a novel method to detect and correct drift in non-raster scanning
      probe microscopy. In conventional raster scanning drift is usually corrected by
      subtracting a fitted polynomial from each scan line, but sample tilt or large
      topographic features can result in severe artifacts. Our method uses self
      intersecting scan paths to distinguish drift from topographic features. Observing
      the height differences when passing the same position at different times enables
      the reconstruction of a continuous function of drift. We show that a small number
      of self-intersections is adequate for automatic and reliable drift correction.
      Additionally, we introduce a fitness function which provides a quantitative
      measure of drift correctability for any arbitrary scan shape. 

PMID- 24295800
TI  - Surgical approaches in total knee arthroplasty: a meta-analysis comparing the
      midvastus and subvastus to the medial peripatellar approach.
AB  - Subvastus, midvastus and medial parapatellar approaches are the most popular
      approaches in total knee arthroplasty (TKA). However, the superior approach in
      TKA still remains controversial. We therefore conducted a meta-analysis to
      quantitatively compare the midvastus and subvastus approaches to the medial
      parapatellar approach in TKA. A total of 32 randomized controlled trials (RCTs)
      with 2451 TKAs in 2129 patients were included in this study. The meta-analysis
      suggested that, when compared with the medial parapatellar approach, the
      midvastus approach showed better outcomes in pain and knee range of motion at
      postoperative 1-2weeks but also was associated with longer operative time; the
      subvastus approach showed better outcomes in knee range of motion at
      postoperative 1week, straight leg raise and lateral retinacular release. 

PMID- 24295801
TI  - Last decade in THA: unsettling and disappointing.

PMID- 24295802
TI  - Periprosthetic fracture torque for short versus standard cemented hip stems: an
      experimental in vitro study.
AB  - In an attempt to preserve proximal femoral bone stock and achieve a better fit in
      smaller femora, especially in the Asian population, several new shorter stem
      designs have become available. We investigated the torque to periprosthetic
      femoral fracture of the Exeter short stem compared with the conventional length
      Exeter stem in a Sawbone model. Forty-two stems; 21 shorter and 21 conventional
      stems both with three different offsets were cemented in a composite Sawbone
      model and torqued to fracture. Results showed that Sawbone femurs break at a
      statistically significantly lower torque to failure with a shorter compared to
      conventional-length Exeter stem of the same offset. Both standard and short-stem
      designs are safe to use as the torque to failure is 7-10 times that seen in
      activities of daily living. 

PMID- 24295803
TI  - Novel vaccination approaches against equine alphavirus encephalitides.
AB  - The current production of inactivated vaccines for the prevention of equine
      alphavirus encephalitides caused by Eastern, Western and Venezuelan Equine
      Encephalitis viruses (EEEV, WEEV, VEEV) involves the manipulation of large
      quantities of infectious viral particles under biosafety level 3 containment
      laboratories with the potential risk of transmission to the operators. Moreover,
      these vaccines are not capable of inducing a long-lasting immunity. Modified live
      vaccines, which were also attempted, maintain residual virulence and
      neurotropism, causing disease in both horses and humans. Therefore, the
      production of an efficacious second generation vaccine which could be used in the
      prevention of alphavirus infection without the need to manipulate infectious
      viral particles under high biocontainment conditions could be of great benefit
      for the worldwide horse industry. Furthermore, equine alphaviruses are considered
      as biological threat agents. Subunit, chimeric, gene-deleted live mutants, DNA
      and adenovirus-vectored alphavirus vaccines have been evaluated; such approaches
      are reviewed in this work. Climate changes, together with modifications in bird
      and vector ecology, are leading to the arise of emerging pathogens in new
      geographical locations, and these zoonotic New World arboviruses are gaining
      concern. Novel vaccine development does show a promising future for prevention of
      these infections in both horses and humans.

PMID- 24295804
TI  - Literature review of HPV vaccine delivery strategies: considerations for school-
      and non-school based immunization program.
AB  - School-based vaccination is becoming a more widely considered method of
      delivering HPV immunizations to an adolescent population; however, many countries
      do not have experience with delivering adolescent vaccines or school-based
      programs. This literature review will summarize the experiences from countries
      implementing non-health facility-based and health facility-based vaccination
      programs and assess HPV vaccine coverage. In October 2012, a systematic search in
      PubMed for studies related to the evaluation of national/regional, pilot, or
      demonstration HPV immunization programs that worked within existing health system
      yielded nine articles, representing seventeen countries. School-based programs
      achieved high HPV vaccination coverage rates in 9 to 13-year-old girls across the
      different studies and geographic locations, suggesting non-health facility-based
      programs are possible for HPV vaccine introduction. Grade-based, compared to age
      based, eligibility criteria may be easier to implement in school settings. More
      studies are needed to explore the methods to standardize estimates for HPV
      vaccine coverage so that programs can be appropriately evaluated.

PMID- 24295805
TI  - Development of immunization trials against Pasteurella multocida.
AB  - Pasteurellosis is one of the most important respiratory diseases facing
      economically valuable farm animals such as poultry, rabbit, cattle, goats and
      pigs. It causes severe economic loss due to its symptoms that range from primary
      local infection to fatal septicemia. Pasteurella multocida is the responsible
      pathogen for this contagious disease. Chemotherapeutic treatment of Pasteurella
      is expensive, lengthy, and ineffective due to the increasing antibiotics
      resistance of the bacterium, as well as its toxicity to human consumers. Though,
      biosecurity measures played a role in diminishing the spread of the pathogen, the
      immunization methods were always the most potent preventive measures. Since the
      early 1950s, several trials for constructing and formulating effective vaccines
      were followed. This up-to-date review classifies and documents such trials. A
      section is devoted to discussing each group benefits and defects. 

PMID- 24295806
TI  - Economic evaluations of implemented vaccination programmes: key methodological
      challenges in retrospective analyses.
AB  - Post-implementation evaluation should play an important role in assessing the
      success of public health programmes; however, the value for money achieved by
      vaccine programmes after introduction has received relatively little attention to
      date. In this article we explore the methodological challenges in these analyses
      and offer direction for future evaluations in the area. We identify alternative
      approaches to addressing these challenges, which include the estimation of
      disease changes attributable to vaccination efforts, the hypothetical no
      vaccination comparator scenario and the full benefit achieved by implemented
      vaccination programmes. We also outline other important considerations such as
      the evolution of prices over time. Further work needs to be done to explore these
      issues and to determine how the application of different approaches may impact on
      the results of evaluations in various circumstances. As retrospective analyses
      are likely to become more frequent and influential, it is important that both the
      benefits and the limitations of post-implementation evaluations are recognised
      and understood. We argue that it would be useful to establish a methodological
      framework to provide standards and guidance on how to undertake such analyses in
      the future. 

PMID- 24295807
TI  - Antibody response to human papillomavirus vaccine in subjects with inherited bone
      marrow failure syndromes.
AB  - Patients with Fanconi anemia (FA) and other inherited bone marrow failure
      syndromes (IBMFS) have extremely high risks of squamous cell head and neck, and
      gynecologic carcinomas. In the general population, these sites are often
      associated with infection with human papillomaviruses (HPV), particularly HPV16
      and HPV18. Our objectives were to measure the levels of HPV antibodies in
      unvaccinated patients, and to determine whether these patients developed and
      maintained similar levels of antibodies as those observed in healthy women,
      following vaccination with the currently licensed HPV L1 virus-like particles
      (VLP) vaccines. We measured anti-HPV IgG antibody levels in sera from patients
      using an HPV16 or HPV18 L1 VLP enzyme-linked immunoabsorbent assay. Most
      unvaccinated patients did not have detectable antibody levels, except for a few
      women above age 25. Both FA and other IBMFS patients developed antibody levels
      following vaccination that were similar to those previously described in healthy
      women, and those levels appeared to be sustained out to 5 years after
      immunization. Thus, antibody responses to the HPV L1 VLP vaccine in patients with
      FA and other IBMFS appeared to be similar to the responses reported in the
      general population, implying potential efficacy against future infections with
      the HPV types contained in the vaccine. 

PMID- 24295808
TI  - Nanoparticle vaccines.
AB  - Nanotechnology increasingly plays a significant role in vaccine development. As
      vaccine development orientates toward less immunogenic "minimalist" compositions,
      formulations that boost antigen effectiveness are increasingly needed. The use of
      nanoparticles in vaccine formulations allows not only improved antigen stability
      and immunogenicity, but also targeted delivery and slow release. A number of
      nanoparticle vaccines varying in composition, size, shape, and surface properties
      have been approved for human use and the number of candidates is increasing.
      However, challenges remain due to a lack of fundamental understanding regarding
      the in vivo behavior of nanoparticles, which can operate as either a delivery
      system to enhance antigen processing and/or as an immunostimulant adjuvant to
      activate or enhance immunity. This review provides a broad overview of recent
      advances in prophylactic nanovaccinology. Types of nanoparticles used are
      outlined and their interaction with immune cells and the biosystem are discussed.
      Increased knowledge and fundamental understanding of nanoparticle mechanism of
      action in both immunostimulatory and delivery modes, and better understanding of
      in vivo biodistribution and fate, are urgently required, and will accelerate the
      rational design of nanoparticle-containing vaccines.

PMID- 24295809
TI  - Effect of sucrose availability and pre-running on the intrinsic value of wheel
      running as an operant and a reinforcing consequence.
AB  - The current study investigated the effect of motivational manipulations on
      operant wheel running for sucrose reinforcement and on wheel running as a
      behavioral consequence for lever pressing, within the same experimental context.
      Specifically, rats responded on a two-component multiple schedule of
      reinforcement in which lever pressing produced the opportunity to run in a wheel
      in one component of the schedule (reinforcer component) and wheel running
      produced the opportunity to consume sucrose solution in the other component
      (operant component). Motivational manipulations involved removal of sucrose
      contingent on wheel running and providing 1h of pre-session wheel running.
      Results showed that, in opposition to a response strengthening view, sucrose did
      not maintain operant wheel running. The motivational operations of withdrawing
      sucrose or providing pre-session wheel running, however, resulted in different
      wheel-running rates in the operant and reinforcer components of the multiple
      schedule; this rate discrepancy revealed the extrinsic reinforcing effects of
      sucrose on operant wheel running, but also indicated the intrinsic reinforcement
      value of wheel running across components. Differences in wheel-running rates
      between components were discussed in terms of arousal, undermining of intrinsic
      motivation, and behavioral contrast. 

PMID- 24295810
TI  - Carnosic acid suppresses the production of amyloid-beta 1-42 and 1-43 by inducing
      an alpha-secretase TACE/ADAM17 in U373MG human astrocytoma cells.
AB  - Amyloid beta (Abeta) peptides are key molecules in the pathogenesis of
      Alzheimer's disease (AD). The sequential cleavage of amyloid precursor protein
      (APP) by the beta- and gamma-secretases generates Abeta peptides; however, the
      alternate cleavage of APP by the alpha- and gamma-secretases decreases Abeta
      production. We previously reported that carnosic acid (CA), a phenolic diterpene
      compound found in the labiate herbs rosemary and sage, suppresses Abeta (1-40 and
      1-42) production by activating alpha-secretase in cultured SH-SY5Y human
      neuroblastoma cells (Neurosci. Res. 2013; 75: 94-102). Here, we investigated the
      effect of CA on the production of Abeta peptides (1-40, 1-42 and 1-43) in U373MG
      human astrocytoma cells. The treatment of cells with CA suppressed Abeta40/42/43
      release (55-71% decrease at 50MUM). CA treatment enhanced the mRNA expressions of
      an alpha-secretase TACE (tumor necrosis factor-alpha-converting enzyme, also
      called a disintegrin and metalloproteinase-17, ADAM17); however, the beta
      secretase BACE1 (beta-site APP-cleaving enzyme-1) was not increased by CA.
      Knockdown of TACE by siRNA reduced soluble-APPalpha release enhanced by CA and
      partially recovered the CA-suppressed Abeta40/42/43 release. These results
      suggest that CA reduces Abeta production, at least partially, by activating TACE
      in human astroglial cells. The use of CA may have a potential in the prevention
      of Abeta-mediated diseases. 

PMID- 24295811
TI  - Characteristics of magnetic resonance imaging biomarkers in a natural history
      study of golden retriever muscular dystrophy.
AB  - The goal of this study was to assess whether magnetic resonance imaging (MRI)
      biomarkers can quantify disease progression in golden retriever muscular
      dystrophy (GRMD) via a natural history study. The proximal pelvic limbs of ten
      GRMD and eight normal dogs were scanned at 3, 6, and 9-12 months of age. Several
      MRI imaging and texture analysis biomarkers were quantified in seven muscles.
      Almost all MRI biomarkers readily distinguished GRMD from control dogs; however,
      only selected biomarkers tracked with longitudinal disease progression. The
      biomarkers that performed best were full-length muscle volume and a texture
      analysis biomarker, termed heterogeneity index. The biceps femoris,
      semitendinosus and cranial sartorius muscles showed differential progression in
      GRMD versus control dogs. MRI features in GRMD dogs showed dynamic progression
      that was most pronounced over the 3- to 6-month period. Volumetric biomarkers and
      water map values correlated with histopathological features of
      necrosis/regeneration at 6-months. In conclusion, selected MRI biomarkers (volume
      and heterogeneity index) in particular muscles (biceps femoris, semitendinosus,
      and cranial sartorius) adjusted for age effect allow distinction of differential
      longitudinal progression in GRMD dogs. These biomarkers may be used as surrogate
      outcome measures in preclinical GRMD trials.

PMID- 24295812
TI  - Respiratory dysfunction in unsedated dogs with golden retriever muscular
      dystrophy.
AB  - Golden retriever muscular dystrophy (GRMD) is a well-established model of
      Duchenne muscular dystrophy. The value of this model would be greatly enhanced
      with practical tools to monitor progression of respiratory dysfunction during
      treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and
      respiratory inductance plethysmography (RIP) were performed to determine if
      quantifiable abnormalities could be identified in unsedated, untrained, GRMD
      dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched
      carriers were compared. Arterial blood gas analysis was successfully performed in
      all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs.
      Partial pressure of carbon dioxide and bicarbonate concentration were higher in
      GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD
      dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each
      technique provided objective, quantifiable measures that will be useful for
      monitoring respiratory function in GRMD dogs during clinical trials while
      avoiding the influence of sedation on results. Increased expiratory flows and the
      pattern of abdominal breathing are novel findings, not reported in people with
      Duchenne muscular dystrophy, and might be a consequence of hyperinflation. 

PMID- 24295813
TI  - Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor
      mutation at the alpha-epsilon subunit interface.
AB  - Congenital myasthenic syndromes (CMS) result from the failure to achieve muscle
      depolarisation due to disorders in the structure and/or function of the
      neuromuscular synapse. Mutations of the nicotinic acetylcholine receptor (nAChR)
      form a major subset of CMS. We describe a patient who presented with recurrent
      apnoeic crises in the neonatal period requiring ventilator support.
      Electromyography revealed compound muscle action potential decrement upon
      repetitive stimulation. Sequencing of nAChR subunit genes revealed two missense
      mutations. One previously reported null mutation p.epsilonTyr15His, and a second
      novel missense mutation, p.epsilonThr38Lys, that is well expressed in mammalian
      cell culture and thus likely to exert its effect via alteration of ion channel
      kinetics. Functional analysis revealed abbreviated ion channel bursts
      characteristic of a fast channel CMS. The mutation p.epsilonThr38Lys occurs at
      the interface between the alpha and epsilon subunits of the nAChR pentamer and
      leads to instability of the open channel. The effects of this mutation on channel
      function were investigated in relation to other fast channel mutants at an
      analogous subunit interface within the nAChR pentamer. Fast channel syndromes are
      frequently characterised by severe myasthenic weakness with apnoeic crises;
      knowledge of the underlying mutation and its functional consequences can be vital
      for appropriate therapy and patient management. 

PMID- 24295814
TI  - Compound heterozygous mutations of the TNXB gene cause primary myopathy.
      Response.

PMID- 24295815
TI  - Type 2 diabetes mellitus in children and adolescents.
AB  - On the basis of strong research evidence and consensus, type 1 diabetes mellitus
      (DM) remains the most common form of DM in children and adolescents. The
      incidence of type 2 DM in the pediatric population is rapidly increasing because
      of the obesity epidemic, and minority groups are disproportionately affected. (2)
      (10) (19) On the basis of some research evidence and consensus, it can be
      challenging to initially differentiate between type 2 DM and type 1 DM clinically
      because of the increased prevalence of obesity, the complex interplay of
      autoimmunity and obesity, and common symptoms at presentation. (1) (10) (19)
      Significant evidence and consensus support a genetic basis for the development of
      type 2 DM in children. Physicians should routinely screen at risk children older
      than age 10 years for DM. Screening criteria include obesity, a family history of
      type 2 DM, a minority racial or ethnic background, acanthosis nigricans, or other
      diseases associated with insulin resistance, including polycystic ovary syndrome,
      hypertension, or dyslipidemia. (1) (10) (18) (19) On the basis of consensus,
      diagnosis of type 2 DM can be confirmed by an elevated fasting blood glucose
      level greater than 126 mg/dl (7.0 mmol/L), an elevated 2-hour plasma glucose
      greater than 200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test, an
      elevated random blood glucose greater than 200 mg/dL (11.1 mmol/L), or a
      hemoglobin A1c level greater than 6.5% with suggestive symptoms. (10) According
      to strong research evidence and consensus, once the diagnosis has been made,
      treatment should be based on the acuity of presentation and should focus on
      lifestyle modification and on normalizing hyperglycemia to minimize
      complications. Metformin is currently first-line treatment for type 2 DM in
      children and adolescents older than age 10 years who present nonacutely. (18)
      (19) Strong research evidence and consensus demonstrate that because type 2 DM
      has an insidious onset, microvascular and macrovascular complications can be
      present at the time of diagnosis. Patients should be screened for the presence of
      complications when the diagnosis of type 2 DM is made and in follow-up. (6) (10).

PMID- 24295816
TI  - Managing feeding problems and feeding disorders.
AB  - On the basis of strong research evidence, feeding problems and feeding disorders
      are common,especially in children who have developmental disabilities. (1) (3) On
      the basis of strong research evidence, a variety of prenatal, medical,
      environmental, behavioral, and parental factors contribute to childhood feeding
      disorders. (1) (3) On the basis of some research evidence plus consensus, many
      feeding problems are preventable or easily treated.On the basis of strong
      research evidence, left untreated, feeding disorders may result in complications,
      including aspiration pneumonitis,failure to thrive, and parent-child conflict. On
      the basis of some research evidence plus consensus,treatment of feeding disorders
      improves nutritional status, growth, feeding safety, and quality of life.

PMID- 24295817
TI  - Human metapneumovirus.
AB  - On the basis of strong research evidence and consensus, (1) (2) (3) (4) human
      metapneumovirus is a leading cause of upper and lower respiratory tract
      infections in children. On the basis of research evidence and consensus, (3) (5)
      (6) (7) the clinical features of MPV-associated disease are similar to those of
      RSV. MPV is an important cause of asthma exacerbations, bronchiolitis, and
      pneumonia. Bacterial superinfection can occur.On the basis of research evidence
      and consensus, (2) (3) (8) the mean age of infection is 6 to 12 months, and
      nearly all school-age children are seropositive. However, infection can recur,
      likely in part due to impaired CD8+ T-cell response. On the basis of research
      evidence and consensus, (9) (10) (11) morbidity and mortality are the highest in
      patients who are premature, are immunosuppressed, or have underlying
      cardiopulmonary abnormalities. On the basis of research evidence and consensus,
      (2) commercially available diagnostic tests exist, and reverse transcriptase-PCR
      is the most commonly used. On the basis of consensus, because of a lack of
      relevant clinical studies, recombinant virus vaccines and monoclonal antibodies
      may be useful as prophylactics or therapeutics. (10)

PMID- 24295819
TI  - Index of suspicion.

PMID- 24295820
TI  - Down syndrome.

PMID- 24295821
TI  - Visual diagnosis: an 11-month-old with nausea, vomiting, and an abdominal mass.
AB  - Children with intussusception can present with a wide variety of symptoms,
      including vomiting, fever,lethargy, and abdominal pain. The classic triad of
      abdominal pain, hematochezia, and palpable abdominal mass is seen in a few
      patients.* Early diagnosis of intussusception depends on a high level of clinical
      suspicion in any child with non specific abdominal findings followed by
      appropriate radiographic or ultrasonographic evaluation and confirmation with a
      contrast enema.* Abdominal radiography, although an appropriate component of the
      initial workup for gastrointestinal symptoms, lacks the sensitivity to reliably
      exclude the presence of intussusception.* Because ultrasonography is a safe,
      sensitive, and specific test for the diagnosis of intussusceptions, it should be
      performed early whenever there is clinical suspicion of intussusception.*
      Contrast enema is the gold standard for diagnosis and first-line treatment of
      intussusception. There is an increasing trend for pneumatic reduction of
      intussusception compared with hydrostatic reduction.Intravenous placement, fluid
      resuscitation, and notification of the pediatric surgeon should be completed
      before contrast enema.

PMID- 24295822
TI  - TaqManR proximity ligation technology for the detection of heterodimeric adhesion
      receptors on lymphocytes.
AB  - TaqMan(R) proximity ligation technology (TaqMan(R) PLA) is an innovative
      advancement of immuno PCR. It allows a fast and quantitative detection of vicinal
      proteins or protein-protein interactions from cell lysates by combining antibody
      antigen binding with a real-time PCR detection. We tested if TaqMan(R) PLA also
      was applicable to investigate and relatively quantitate adhesion receptor
      heterodimers such as the alpha-4/beta-1 integrin on the surface of intact cells.
      Both, alpha-4, beta-1 and the alpha-4/beta-1 heterodimer were detected on the
      surface of lymphocytes by TaqMan(R) PLA. Results were specific, reproducible and
      comparable to flow cytometric data. However, preciseness of reactions varied
      dependent on the antibody pairs used. Co-detection of proximate identical
      subunits suggested clusters of alpha-4 and/or beta-1 on the cell surface which we
      confirmed by microscopy. We conclude that real-time PCR-based TaqMan(R) PLA is of
      limited applicability to investigate heterodimeric receptor molecules such as the
      alpha-4/beta-1 integrin. Determination of an abundance ratio of alpha-4/beta-1 in
      relation to total alpha-4 or beta-1 was not possible and real-time detection did
      not allow conclusions on the surface distribution of molecules. The related in
      situ PLA developed for microscopy allows visualizing proximate protein
      interactions and might be an interesting alternative for research into receptor
      heterodimers and their surface distribution on immune cells. 

PMID- 24295823
TI  - Systematic study of genes influencing cellular chain length in Streptococcus
      sanguinis.
AB  - Streptococcus sanguinis is a Gram-positive bacterium that is indigenous to the
      oral cavity. S. sanguinis, a primary colonizer of the oral cavity, serves as a
      tether for the attachment of other oral pathogens. The colonization of microbes
      on the tooth surface forms dental plaque, which can lead to the onset of
      periodontal disease. We examined a comprehensive mutant library to identify genes
      related to cellular chain length and morphology using phase-contrast microscopy.
      A number of hypothetical genes related to the cellular chain length were
      identified in this study. Genes related to the cellular chain length were
      analysed along with clusters of orthologous groups (COG) for gene functions. It
      was discovered that the highest proportion of COG functions related to cellular
      chain length was 'cell division and chromosome separation'. However, different
      COG functions were also found to be related with altered cellular chain length.
      This suggested that different genes related with multiple mechanisms contribute
      to the cellular chain length in S. sanguinis SK36. 

PMID- 24295824
TI  - Molecular genetic analysis of vesicular transport in Aspergillus niger reveals
      partial conservation of the molecular mechanism of exocytosis in fungi.
AB  - The filamentous fungus Aspergillus niger is an industrially exploited protein
      expression platform, well known for its capacity to secrete high levels of
      proteins. To study the process of protein secretion in A. niger, we established a
      GFP-v-SNARE reporter strain in which the trafficking and dynamics of secretory
      vesicles can be followed in vivo. The biological role of putative A. niger
      orthologues of seven secretion-specific genes, known to function in key aspects
      of the protein secretion machinery in Saccharomyces cerevisiae, was analysed by
      constructing respective gene deletion mutants in the GFP-v-SNARE reporter strain.
      Comparison of the deletion phenotype of conserved proteins functioning in the
      secretory pathway revealed common features but also interesting differences
      between S. cerevisiae and A. niger. Deletion of the S. cerevisiae Sec2p
      orthologue in A. niger (SecB), encoding a guanine exchange factor for the GTPase
      Sec4p (SrgA in A. niger), did not have an obvious phenotype, while SEC2 deletion
      in S. cerevisiae is lethal. Similarly, deletion of the A. niger orthologue of the
      S. cerevisiae exocyst subunit Sec3p (SecC) did not result in a lethal phenotype
      as in S. cerevisiae, although severe growth reduction of A. niger was observed.
      Deletion of secA, secH and ssoA (encoding SecA, SecH and SsoA the A. niger
      orthologues of S. cerevisiae Sec1p, Sec8p and Sso1/2p, respectively) showed that
      these genes are essential for A. niger, similar to the situation in S.
      cerevisiae. These data demonstrate that the orchestration of exocyst-mediated
      vesicle transport is only partially conserved in S. cerevisiae and A. niger. 

PMID- 24295825
TI  - Raw data from clinical trials: within reach?
AB  - Making raw data from clinical trials widely publically available should reduce
      selective reporting biases and enhance the reproducibility of and trust in
      clinical research. The optimal procedures for data sharing are hotly debated.
      Some of the caveats and limitations in proposed data-sharing policies are
      potentially restrictive, and we argue in favor of more widespread availability of
      data from clinical research. 

PMID- 24295826
TI  - [Influence of the physiological medium on the mechanical properties of bone
      cement: can current studies be extrapolated?].
AB  - PURPOSE: The use of bone cement is widespread in orthopaedic surgery. Most of the
      mechanical tests are performed in dry medium, making it difficult to extrapolate
      the results. The objective of this study is to assess if the mechanical
      properties of polymethylmethacrylate (PMMA), obtained in previous reports, are
      still present in a liquid medium. MATERIAL AND METHOD: An experimental study was
      designed with antibiotic (vancomycin) loaded PMMA. Four groups were defined
      according to the medium (dry or liquid) and the pre-conditioning in liquid medium
      (one week or one month). Wear and flexural strength tests were performed
      according to ASTM and ISO standards. Volumetric wear, friction coefficient,
      tensile strength, and Young's modulus were analyzed. All samples were examined by
      scanning electron microscopy. RESULTS: The samples tested in liquid medium showed
      lower wear and flexural strength values (P<.05). The kind of wear was modified
      from abrasive to adhesive in those samples studied in liquid medium. The samples
      with a pre-conditioning time showed lower values of wear (P<.05). CONCLUSIONS:
      Caution is recommended when extrapolating the results of previous PMMA results.
      The different mechanical strength of the cement in a liquid medium, observed in
      saline medium, is much closer to the clinical situation.

PMID- 24295827
TI  - The newly found functions of MTOC in immunological response.
AB  - The MTOCs are present in all eukaryotic cells. In animal somatic cells, the MTOC
      function is played by a centrosome, which contains centrioles and PCM. The
      traditional view is that the MTOC is responsible for the organization of
      microtubular structures (the intracellular network, cilia, and flagella) in
      interphase cells, and the formation of the mitotic and meiotic spindle apparatus
      which is required for the partitioning of chromosomes in dividing cells. Recent
      evidence suggests that MTOC also plays a key role in the engagement of molecular
      motors, directional transport of granules, and polarization of subcellular
      structures and molecules. All of these functions are crucial for targeted
      cytotoxicity and the regulation of immune cells. In this review, we focus on the
      ultrastructural and molecular aspects of MTOCs in various aspects of immune cell
      functions, with specific emphasis on the formation of the IS and targeted cell
      killing. 

PMID- 24295828
TI  - Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL
      uptake.
AB  - AIM is expressed by macrophages in response to agonists of the nuclear receptors
      LXR/RXR. In mice, it acts as an atherogenic factor by protecting macrophages from
      the apoptotic effects of oxidized lipids. In humans, it is detected in
      atherosclerotic lesions, but no role related to atherosclerosis has been
      reported. This study aimed to investigate whether the role of hAIM extends beyond
      inhibiting oxidized lipid-induced apoptosis. To accomplish this goal, functional
      analysis with human monocytic THP1 cells and macrophages differentiated from
      peripheral blood monocytes were performed. It was found that hAIM reduced oxLDL
      induced macrophage apoptosis and increased macrophage adhesion to endothelial
      ICAM-1 by enhancing LFA-1 expression. Furthermore, hAIM increased foam cell
      formation, as shown by Oil Red O and Nile Red staining, as well as quantification
      of cholesterol content. This was not a result of decreased reverse cholesterol
      transport, as hAIM did not affect the efflux significantly from [(3)H]
      Cholesterol-laden macrophages driven by plasma, apoA-I, or HDL2 acceptors.
      Rather, flow cytometry studies indicated that hAIM increased macrophage
      endocytosis of fluorescent oxLDL, which correlated with an increase in the
      expression of the oxLDLR CD36. Moreover, hAIM bound to oxLDL in ELISA and
      enhanced the capacity of HEK-293 cells expressing CD36 to endocytose oxLDL, as
      studied using immunofluorescence microscopy, suggesting that hAIM serves to
      facilitate CD36-mediated uptake of oxLDL. Our data represent the first evidence
      that hAIM is involved in macrophage survival, adhesion, and foam cell formation
      and suggest a significant contribution to atherosclerosis-related mechanisms in
      the macrophage. 

PMID- 24295829
TI  - Replenishment of the B cell compartment after doxorubicin-induced hematopoietic
      toxicity is facilitated by STAT1.
AB  - STAT1 serves as an important regulator in the response to pathogens, oncogenic
      transformation, and genotoxic insults. It exerts these effects by shaping the
      innate and adaptive immune response and by participating in genotoxic stress
      pathways, leading to apoptosis and inhibition of cell proliferation. We have
      investigated the role of STAT1 in hematopoietic toxicity induced by doxorubicin
      in STAT1-proficient and -deficient mice. Whereas the early genotoxic effect of
      doxorubicin did not depend on STAT1, expression of STAT1 was required for
      efficient B lymphocyte repopulation in the recovery phase. We found a lower
      abundance of lymphocyte precursors in the BM of STAT1-deficient animals, which
      was particularly evident after doxorubicin-induced hematopoietic toxicity. In
      accordance, colony-forming assays with STAT1-deficient BM cells revealed a
      decreased number of pre-B colonies. Differentiation from the pro-B to the pre-B
      stage was not affected, as demonstrated by unaltered differentiation of purified
      B cell precursors from BM in the presence of IL-7. With the exception of Sca-1,
      expression of genes implicated in early lymphocyte development in pro-B cells did
      not depend on STAT1. Our findings indicate a specific requirement for STAT1 in
      lymphoid development before differentiation to pre-B cells, which becomes
      particularly apparent in the recovery phase from doxorubicin-induced
      hematopoietic toxicity. 

PMID- 24295830
TI  - Molecular mechanisms regulating the synergism between IL-32gamma and NOD for the
      activation of eosinophils.
AB  - IL-32 is a proinflammatory cytokine associated with infections, autoimmune
      diseases, and allergic asthma. In the present study, we elucidated the
      synergistic effect of IL-32gamma and NOD ligand on the activation of human
      eosinophils, principal effector cells for allergic inflammation, and the
      underlying mechanisms. Specific IL-32-binding protein, PR3, was found to localize
      on the cell surface and in the cytoplasm of eosinophils. IL-32gamma was more
      capable of activating eosinophils than its isotype variant IL-32alpha and
      exhibited synergistic effect with NOD1 ligand iE-DAP and NOD2 ligand MDP on the
      induction of allergic inflammation-related IL-1beta, TNF-alpha, and chemokines
      CXCL8, CCL3, and CCL4 (P<0.05). Moreover, IL-32gamma and iE-DAP or MDP induced
      the significant up-regulation of the cell-surface expression of adhesion molecule
      CD18 and ICAM-1 on eosinophils. Synergism between IL-32gamma and NOD ligands was
      dependent on the activation of intracellular caspase 1, ERKs, p38 MAPK, and NF
      kappaB pathways in eosinophils. The further-enhanced CD18 and ICAM-1 expression
      and production of cytokines and chemokines were observed in eosinophils
      cocultured with human bronchial epithelial BEAS-2B cells. Furthermore, combined
      treatment of IL-32gamma and NOD ligand could activate the release of eosinophil
      extracellular DNA traps, thereby implying the pathogen-defense mechanisms of
      eosinophils. Together, the above study provides pivotal immunological mechanisms
      by which bacterial infection-mediated activation of NOD1,2, together with IL
      32gamma, can synergize the activation of eosinophils interacting with bronchial
      epithelial cells. 

PMID- 24295832
TI  - Soluble antigen traffics rapidly and selectively from the corneal surface to the
      eye draining lymph node and activates T cells when codelivered with CpG
      oligonucleotides.
AB  - The transport of antigen to the secondary lymphoid tissue is a central component
      in the initiation of the adaptive immune response. The mechanism of antigen
      delivery to the DLN from the avascular cornea has not been fully explored.
      Previous studies in the mouse have shown that cell-associated corneal antigen is
      delivered within 6 h to the eye draining SM DLN via DCs and macrophages. In this
      study, we used a system in which antigen and the processed p-MHCII complexes
      derived from the antigen could be tracked in vivo. We report that soluble antigen
      applied to an abraded cornea in the mouse is transported rapidly (within 30 min)
      to the SM DLN, where a proportion is taken up by resident DCs and presented as p
      MHCII complexes, while the larger part is cleared by 8 h. At a later time, a
      second wave of antigen transport in migratory DCs enters the DLN and participates
      in further continued antigen presentation. With the use of an antigen-specific
      TCR transgenic mouse system, we demonstrate that T cell activation does not occur
      during the early stages of soluble antigen delivery to LN, even though p-MHCII
      complexes are generated. Antigen-specific T cell activation occurs in the later,
      presumed cell-associated phase but requires codelivery of a "danger" signal, such
      as the TLR ligand CpG. We suggest that the early delivery of soluble antigen is
      more likely to induce T cell nonresponsiveness (anergy) unless presented in the
      context of an innate-immune cell activation (danger) signal. 

PMID- 24295831
TI  - Regulation of the mucosal phenotype in dendritic cells by PPARgamma: role of
      tissue microenvironment.
AB  - Mucosal DCs play a critical role in tissue homeostasis. Several stimuli can
      induce a mucosal phenotype; however, molecular pathways that regulate development
      of mucosal DC function are relatively unknown. This study sought to determine
      whether PPARgamma contributes to the development of the "mucosal" phenotype in
      mouse DCs. Experiments demonstrated that PPARgamma activation in BMDCs induced an
      immunosuppressive phenotype in which BMDCs had reduced expression of MHC class II
      and costimulatory molecules, increased IL-10 secretion, and reduced the ability
      to induce CD4 T cell proliferation. Activation of PPARgamma enhanced the ability
      of BMDC to polarize CD4 T cells toward iTregs and to induce T cell expression of
      the mucosal homing receptor, CCR9. Activation of PPARgamma increased the ability
      of BMDCs to induce T cell-independent IgA production in B cells. BMDCs from
      PPARgamma(DeltaDC) mice displayed enhanced expression of costimulatory molecules,
      enhanced proinflammatory cytokine production, and decreased IL-10 synthesis.
      Contrary to the inflammatory BMDC phenotype in vitro, PPARgamma(DeltaDC) mice
      showed no change in the frequency or phenotype of mDC in the colon. In contrast,
      mDCs in the lungs were increased significantly in PPARgamma(DeltaDC) mice. A
      modest increase in colitis severity was observed in DSS-treated
      PPARgamma(DeltaDC) mice compared with control. These results indicate that
      PPARgamma activation induces a mucosal phenotype in mDCs and that loss of
      PPARgamma promotes an inflammatory phenotype. However, the intestinal
      microenvironment in vivo can maintain the mucosal DC phenotype of via PPARgamma
      independent mechanisms. 

PMID- 24295833
TI  - Balanitis xerotica obliterans in children and adolescents: a literature review
      and clinical series.
AB  - OBJECTIVE: Balanitis xerotica obliterans (BXO) is a chronic inflammatory disease
      that is considered as male genital variant lichen sclerosis. The incidence varies
      greatly in different series; diagnosis is mostly clinical but histopathological
      confirmation is mandatory. Various treatments are described, but there is no
      consensus that one is the best. MATERIALS AND METHODS: A literature review was
      made of BXO and lichen sclerosis in boys under 18 years of age, between 1995 and
      2013, analyzing demographic dates, treatments and outcomes. In addition to that,
      we reviewed BXO cases treated in our centers in the last 10 years. RESULTS: After
      literature review, only 13 articles matched the inclusion criteria. Analyzing
      those selected, the global incidence of BXO is nearly 35% among circumcised
      children. Described symptoms are diverse and the low index of clinical suspicion
      is highlighted. The main treatment is circumcision, with use of topical and
      intralesional steroids and immunosuppressive agents. CONCLUSION: BXO is a
      condition more common than we believe and we must be vigilant to find greater
      number of diagnoses to avoid future complications. The main treatment for BXO is
      circumcision, but as topical or intralesional treatments are now available with
      potentially good outcomes, they may be considered as coadjuvants.

PMID- 24295834
TI  - Hill-Sachs remplissage, an arthroscopic solution for the engaging Hill-Sachs
      lesion: 2- to 10-year follow-up and incidence of recurrence.
AB  - BACKGROUND: This paper presents the results of arthroscopic remplissage in the
      treatment of traumatic anterior shoulder instability in a difficult subgroup of
      patients with both glenoid bone loss and a significant Hill-Sachs lesion.
      METHODS: From March 2002 through May 2010, 270 patients were treated surgically
      for anterior shoulder instability. Of the surgical procedures performed, 59
      patients (21.9%) with anterior instability and Bigliani grade IIIA (glenoid
      deficiency <25%) were treated with this technique. The average age was 33 years
      (range, 17-67 years); there were 48 men and 11 women. The procedure consisted of
      an arthroscopic posterior capsulodesis and infraspinatus tenodesis that filled
      the Hill-Sachs lesion and a concomitant arthroscopic anterior Bankart repair.
      Forty-five patients (76%) were available for follow-up ranging from 2 to 10 years
      (average, 58 months). All patients were evaluated by use of the Rowe and Constant
      scores. Twenty-seven patients were also evaluated by use of the Western Ontario
      Shoulder Instability Index. RESULTS: Of the 45 patients, 2 (4.4%) had recurrent
      instability after traumatic dislocations; one was due to a basketball injury, and
      the other was reinjured by wrestling. At final follow-up, the median and mean
      scores +/- standard deviation were as follows: Rowe score, 95, 92 +/- 12;
      Constant score, 95, 92 +/- 10; and Western Ontario Shoulder Instability Index,
      110, 224 +/- 261. All patients, except the traumatic dislocations, had no
      reoperations or complications. CONCLUSION: This procedure provides an effective
      arthroscopic approach in those cases of anterior shoulder instability that
      present with the combination of glenoid bone loss (grade IIIA) and a Hill-Sachs
      lesion. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

PMID- 24295835
TI  - Quantification of the exposure of the glenohumeral joint from the minimally
      invasive to more invasive subscapularis approach to the anterior shoulder: a
      cadaveric study.
AB  - BACKGROUND: There are multiple techniques to approach the glenohumeral joint. Our
      purpose was to quantify the average area of the glenohumeral joint exposed with 3
      subscapularis approaches and determine the least invasive approach for placement
      of shoulder resurfacing and total shoulder arthroplasty instruments. METHODS: Ten
      forequarter cadaveric specimens were used. Subscapularis approaches were
      performed sequentially from split, partial tenotomy, and full tenotomy through
      the deltopectoral approach. Glenohumeral joint digital photographs were analyzed
      in Image J software (National Institutes of Health, Bethesda, MD, USA). Shoulder
      resurfacing and total shoulder arthroplasty instruments were placed on the
      humeral head, and anatomic landmarks were identified. RESULTS: The average area
      of humeral head visible, from the least to the most invasive approach, was 3.2,
      8.1, and 11.0 cm2, respectively. The average area of humeral head visible
      differed significantly according to the approach. Humeral head area increased
      157% when the subscapularis split approach was compared with the partial tenotomy
      approach and 35% when the partial approach was compared with the full tenotomy
      approach. The average area of glenoid exposed from least to most invasive
      approach was 2.0, 2.3, and 2.5 cm2, respectively. No significant difference was
      found between the average area of the glenoid and the type of approach. Posterior
      structures were difficult to visualize for the subscapularis split approach.
      Partial tenotomy of the subscapularis allowed placement of resurfacing in 70% of
      the specimens and total arthroplasty instruments in 90%. CONCLUSIONS: The
      subscapularis splitting approach allows adequate exposure for glenoid-based
      procedures, and the subscapularis approaches presented expose the glenohumeral
      joint in a step-wise manner. LEVEL OF EVIDENCE: Anatomy study, cadaver
      dissection.

PMID- 24295836
TI  - Effect of Bankart repair on the loss of range of motion and the instability of
      the shoulder joint for recurrent anterior shoulder dislocation.
AB  - BACKGROUND: Bankart repair postoperative complications include loss of shoulder
      motion and shoulder instability. The primary reason that postoperative
      complications develop may be excessive imbrication of the anterior band of the
      inferior glenohumeral ligament (AIGHL) or inadequate repair position. The purpose
      of this study was to quantitatively evaluate the influence of inadequate repair
      by computer simulation for a normal shoulder joint. METHODS: Magnetic resonance
      images of 10 normal shoulder joints were acquired for 7 positions every 30
      degrees  from the maximum internal rotation to the maximum external rotation with
      the arm abducted at 90 degrees . The shortest 3-dimensional path of the AIGHL in
      each rotational orientation was calculated. We used computer simulations to
      anticipate the loss of motion and instability by changing the AIGHL length and
      insertion sites on the glenoid. RESULTS: The AIGHL length measured 50 +/- 5 mm at
      the maximum external shoulder rotation. AIGHL shortening by 3, 6, and 9 mm made
      the angle of maximum external rotation 80 degrees , 68 degrees , and 54 degrees ,
      respectively. A superior deviation of 3, 6, and 9 mm on the glenoid insertion
      resulted in a maximum external rotation angle of 85 degrees , 79 degrees , and 77
      degrees . An inferior deviation of 3, 6, and 9 mm produced humeral head
      translation of 1.7, 2.9, and 3.6 mm. CONCLUSION: Simulation of both excessive
      imbrication and deviation of the insertion position led to quantitative
      prediction of the resulting loss of motion and instability. These findings will
      be useful for anticipating complications after Bankart repair. LEVEL OF EVIDENCE:
      Basic science study, computer modeling, imaging.

PMID- 24295837
TI  - Rat rotator cuff tendon-to-bone healing properties are adversely affected by
      hypercholesterolemia.
AB  - BACKGROUND: Rotator cuff tendon tears represent a major component of reported
      orthopaedic injuries. In addition, more than one quarter of U.S. adults either
      currently have high cholesterol levels or have reduced their previously high
      cholesterol levels through the use of pharmaceuticals. Our clinical data have
      already linked hypercholesterolemia to full-thickness rotator cuff tears, and
      experimental data from our laboratory have shown effects on native tendon
      properties in multiple species. The objective of this study was to evaluate
      healing of supraspinatus tendons in our rat rotator cuff injury model. We
      hypothesized that tendon healing would be inferior in rats receiving a high
      cholesterol diet for 6 months compared with those receiving standard chow.
      METHODS: All animals were subjected to a unilateral supraspinatus detachment and
      repair surgery, with contralateral limbs serving as within-animal comparative
      data. Animals continued their respective diet courses, and their supraspinatus
      tendons were biomechanically or histologically evaluated at 2, 4, and 8 weeks
      postoperatively. RESULTS: Biomechanical testing revealed a significant reduction
      in normalized stiffness in hypercholesterolemic rats compared with controls at 4
      weeks after injury, whereas histologic analyses showed no significant differences
      in collagen organization, cellularity, or cell shape between groups. CONCLUSION:
      On the basis of our findings, hypercholesterolemia may have a detrimental
      biomechanical effect on tendon healing in our rat rotator cuff injury and repair
      model. LEVEL OF EVIDENCE: Basic science study, animal model.

PMID- 24295838
TI  - The use of video before arthroscopic shoulder surgery to enhance patient recall
      and satisfaction: a randomized-controlled study.
AB  - BACKGROUND: Historically, the preoperative consultation has consisted of a
      discussion between patient and surgeon. There is a growing literature describing
      efforts to integrate multimedia into surgical patient education. This study aimed
      to assess the efficacy of an educational video tutorial on early learning of
      information specific to patients undergoing shoulder arthroscopy when it was used
      as an adjunct to the standard preoperative consultation. METHODS: This study was
      a surgeon-blinded, randomized controlled trial involving 40 consecutive patients
      requiring shoulder arthroscopy. After a preoperative consultation with an
      orthopaedic surgeon, patients were randomized in a 1:1 ratio to either a control
      group or a treatment group. The treatment group viewed a 10-minute video, which
      covered the expected preoperative, intraoperative, and postoperative experience.
      Immediately afterward, both groups completed a questionnaire measuring
      satisfaction and recall of information received. All patients completed a second
      questionnaire at the first postoperative visit that assessed overall satisfaction
      with their experience. RESULTS: Thirty-four patients were available for follow
      up. The video group (N = 15) answered 87% of the knowledge questions correctly,
      whereas the control group (N = 19) answered only 56% (P = .000). There was
      stronger agreement in the video group that the preoperative consultation
      contained an appropriate amount of information (P = .039). Postoperatively, there
      was agreement that the video was an effective preparation tool for all stages of
      the surgical experience. However, there was no difference between the groups in
      satisfaction with their overall surgical experience. CONCLUSIONS: Video can
      enhance patients' operative experiences and improve their retained knowledge when
      it is used as an adjunct to the preoperative consultation. LEVEL OF EVIDENCE:
      Basic science, education methodology study, devices to improve learning.

PMID- 24295839
TI  - Ultrasound physics.
AB  - Bedside ultrasound has become an important modality for obtaining critical
      information in the acute care of patients. It is important to understand the
      physics of ultrasound in order to perform and interpret images at the bedside.
      The physics of both continuous wave and pulsed wave sound underlies diagnostic
      ultrasound. The instrumentation, including transducers and image processing, is
      important in the acquisition of appropriate sonographic images. Understanding how
      these concepts interplay with each other enables practitioners to obtain the best
      possible images. 

PMID- 24295840
TI  - An introduction to ultrasound equipment and knobology.
AB  - The use of ultrasonography in medical practice has evolved dramatically over the
      last few decades and will continue to improve as technological advances are
      incorporated into daily medical practice. Although ultrasound machine size and
      equipment have evolved, the basic principles and fundamental functions have
      remained essentially the same. This article reviews the general ultrasound
      apparatus design, the most common probe types available, and the system controls
      used to manipulate the images obtained. Becoming familiar with the machine and
      the controls used for image generation optimizes the scans being performed and
      enhances the use of ultrasound in patient care. 

PMID- 24295841
TI  - Cardiac echocardiography.
AB  - Focused cardiac echocardiography has become a critical diagnostic tool for the
      emergency physician and critical care physician caring for patients in shock and
      following trauma to the chest, and those presenting with chest pain and shortness
      of breath,. Cardiac echocardiography allows for immediate diagnosis of
      pericardial effusions and cardiac tamponade, evaluation of cardiac contractility
      and volume status, and detection of right ventricular strain possibly seen with a
      significant pulmonary embolus. This article addresses how to perform cardiac
      echocardiography using the standard windows, how to interpret a focused goal
      directed examination, and how to apply this information clinically at the
      bedside. 

PMID- 24295842
TI  - Thoracic ultrasonography.
AB  - Thoracic ultrasonography (US) has proved to be a valuable tool in the evaluation
      of the patient with shortness of breath, chest pain, hypoxia, or after chest
      trauma. Its sensitivity and specificity for detecting disease is higher than that
      of a chest radiograph, and it can expedite the diagnosis for many emergent
      conditions. This article describes the technique of each thoracic US application,
      illustrating both normal and abnormal findings, as well as discussing the
      literature. Bedside thoracic US has defined imaging benefits in a wide range of
      thoracic disease, and US guidance has been shown to facilitate thoracic and
      airway procedures. 

PMID- 24295843
TI  - The FAST and E-FAST in 2013: trauma ultrasonography: overview, practical
      techniques, controversies, and new frontiers.
AB  - This article reviews important literature on the FAST and E-FAST examinations in
      adults. It also reviews key pitfalls, limitations, and controversies. A practical
      "how-to" guide is presented. Lastly, new frontiers are explored. 

PMID- 24295844
TI  - The CORE scan: concentrated overview of resuscitative efforts.
AB  - Critically ill patients require rapid, accurate assessments and appropriate
      therapeutic interventions to maximize their chances of recovery. Often the cause
      of a patient's decompensation is not readily apparent based solely on history and
      physical examination findings. The Concentrated Overview of Resuscitative Efforts
      (CORE scan) is a compilation of targeted bedside ultrasound exams that should be
      performed during the assessment and management of critically ill patients. The
      CORE scan can be used to help make critical diagnoses and guide resuscitation
      efforts in patients with undifferentiated deterioration. 

PMID- 24295845
TI  - Preface. Ultrasound: Part 1.

PMID- 24295846
TI  - Literature review of baseline study for risk analysis - the landfill leachate
      case.
AB  - There is growing awareness and public concern about environmental impacts of
      waste management and disposal. Environmental policy instruments have been
      strengthened and associated governmental programmes have increased in recent
      years, resulting in high level strategies for waste management. Risk assessment
      is now an essential tool in the prioritisation of environmental and human health
      protection. However, regulators need to compare the full range of risks on a
      sound and consistent basis. Comparing risks from such diverse sources poses a
      significant challenge, and traditional hazard and risk assessments are no longer
      sufficient. Consideration now needs to be given to a much wider range of factors
      if risk assessment is to be used as an aid to more integrated decision-making
      process. For this purpose, baseline study - the foundation of risk assessment -
      can play a crucial role. To date limited research has been conducted on the need,
      parameters, requirements, and constituents of baseline study particularly in the
      context of how, why, and what information is to be collated in order to render
      risk assessments more appropriately integrated and complete. To establish the
      'state-of-the-art' of baseline study, this paper comprehensively reviews the
      literature regarding environmental risk assessment in general terms, and then
      proceeds to review work that is specifically related to landfills and landfill
      leachate, thereby identifying knowledge gaps and shortfall areas. This review
      concludes that a holistic baseline study procedure for waste disposal sites,
      which risk assessors could use for carrying out risk analyses specifically for
      landfill leachate, does not as yet exist. 

PMID- 24295847
TI  - A community-based epidemiological study of health anxiety and generalized anxiety
      disorder.
AB  - This community-based study examined the frequency of worry about personal health
      in respondents with and without generalized anxiety disorder (GAD), and the
      impact of health anxiety on the disorder. A random community-based telephone
      survey of 5118 Chinese respondents aged 18-64 was conducted. A fully structured
      questionnaire covered the DSM-IV-TR criteria of GAD, major depressive episode
      (MDE), eight domains of worry, the seven-item Whiteley Index (WI-7), health
      service use, and socio-demographic information. Worry about personal health
      ranked fifth (75.6%) among eight domains of worries examined. GAD respondents
      with high level of health anxiety were significantly older, less educated, and
      had lower family income. High health anxiety significantly increased the
      occurrence of one-year MDE, previous persistent worry, previous persistent low
      mood, number of domains of worries, number of non-core DSM-IV-TR GAD symptoms,
      health service use, and mistrust of doctors. Health anxiety is common in GAD and
      may signify greater severity of the disorder. 

PMID- 24295848
TI  - Fearful responding to interoceptive exposure in social anxiety disorder.
AB  - There is accumulating evidence suggesting that anxiety sensitivity (AS) may play
      a role in social anxiety disorder (SAD; e.g., Ball, Otto, Pollack, Uccello, &
      Rosenbaum, 1995). Precedent research has demonstrated the role of AS in panic
      disorder and posttraumatic stress disorder, and subsequently, treatment
      techniques aimed at reducing AS (i.e., interoceptive exposure (IE)) have been
      studied in these populations (Schmidt & Trakowski, 2004; Wald & Taylor, 2008).
      The purpose of this study was to examine the types of responses elicited during
      IE exercises among individuals with SAD. This study describes the responses of
      individuals with SAD (n = 37) and nonclinical control participants (n = 28) to
      six IE exercises. Significant differences in responses to the IE exercises were
      found between participants with SAD and nonclinical controls. However, there were
      no significant differences in responses to the exercises among persons with SAD,
      depending on whether the exercises were completed in private versus group
      settings. Similarity to symptoms during naturally occurring anxiety significantly
      predicted fearful responding across all exercises in persons with SAD.
      Implications and directions for future research are discussed.

PMID- 24295849
TI  - Cardiovascular diseases and HCV infection: a simple association or more?

PMID- 24295850
TI  - Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical
      firstline and secondline treatment for Helicobacter pylori in Chinese patients:
      an open label, randomised, crossover trial.
AB  - OBJECTIVE: Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD)
      therapy have been proposed as empirical firstline regimens for Helicobacter
      pylori. We compared the efficacy and tolerability of 10 day SEQ with 10 day
      modified QUAD as both firstline and secondline treatments for H pylori in a
      randomised crossover study. DESIGN: H pylori positive and treatment naive
      patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10
      days, amoxicillin for an initial 5 days, followed by clarithromycin and
      metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth
      subcitrate, tetracycline and metronidazole). H pylori eradication was confirmed
      by urea breath test at 8 weeks. Patients who failed the initial assigned
      treatment were crossed over to receive the alternate regimen. The primary outcome
      was eradication rates of firstline treatment by intention to treat (ITT) and per
      protocol (PP) analyses. RESULTS: 357 patients were randomised to receive either
      SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and
      98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding
      eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%)
      patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline
      treatment were crossed over to the alternate regimen with 100% retreatment
      success. The overall incidence of adverse events was higher in the QUAD (16.7%)
      than in the SEQ (8.1%; p=0.032) group. CONCLUSIONS: Ten day sequential and
      modified bismuth quadruple therapies are both highly effective as empirical
      firstline therapies for H pylori in Chinese patients. CLINICALTRIALSGOV: NCT
      01760824.

PMID- 24295851
TI  - Histology of solid lateral cervical masses biopsied in children.
AB  - INTRODUCTION: Solid cervical lateral neck masses in children may require surgical
      biopsy to confirm appropriate diagnostic and begin a directed therapeutic
      treatment. We aimed to describe the contribution of pathological results and
      compare them with the clinical diagnosis and the paraclinical tools. METHODS: A
      retrospective review of surgical biopsies for solid lateral neck masses in
      children over a ten year period in a pediatric tertiary center was conducted.
      Demographic, imaging, laboratory analysis, surgical and pathological data were
      collected and analyzed using descriptive statistics with SPSS 17.0. RESULTS: 44
      biopsies were done between 2002 and 2012. Inflammatory masses were found in 26/44
      biopsies with half of them (13/26) being nontuberculous mycobacterial (NTM)
      lymphadenitis. Non-inflammatory/benign masses represented 9/44 biopsies and 5/44
      masses were of malignant etiology. Malignant masses imaging had a sensitivity and
      specificity of 33% and 75%, respectively, for ultrasound, whereas Neck CT scan
      had 33% and 77%, respectively. The contribution of pathological results to the
      clinical management was questionable in 39% (17/44) of biopsies. CONCLUSION:
      Inflammatory masses with NTM lymphadenitis were the most common diagnosis.
      Imaging was not helpful in establishing the diagnosis. Heterogeneity in the
      management of solid lateral neck masses between clinicians was important and
      indicates the need for guideline approach.

PMID- 24295853
TI  - Induction of oxidative stress and related transcriptional effects of
      perfluorononanoic acid using an in vivo assessment.
AB  - Perfluorononanoic acid (PFNA) is an organic pollutant ubiquitous in the
      environment. However, the potential toxicity of PFNA remains largely unknown in
      teleost fish. This study defined the oxidative stress and related transcriptional
      effects of PFNA at various concentrations on zebrafish larvae. Activities of
      superoxide dismutase were induced in PFNA-treated groups but attenuated with
      exposure to higher concentration. Catalase activity and lipid peroxidation were
      significantly inhibited or increased at the highest concentration, respectively.
      To test the apoptotic pathway, several genes related to cell apoptosis were
      examined using real-time PCR. The expression of p53, apoptosis-inducing factor
      (AIF) and c-Jun NH (2)-terminal kinase (JNK) was partially increased, while Bcl
      2, an anti-apoptotic gene, was reduced, with no significant effects on Bax and
      caspase-3 during the exposure period. The effect of PFNA on lipid beta-oxidation
      system was investigated by examining the activity of peroxisome fatty acyl-COA
      oxidase (ACOX) and the expression of peroxisome proliferating activating
      receptors (PPARs). ACOX activity was moderately elevated with marginal
      significance and was not a significant consequence of PPARalpha and PPARgamma
      expression. The overall results suggest that turbulence of oxidative stress and
      apoptotic pathway is involved in PFNA-induced toxicity in zebrafish larvae, and
      the gene expression patterns are able to reveal some potential mechanisms of
      developmental toxicity. 

PMID- 24295855
TI  - A closer look at European health care reforms.

PMID- 24295852
TI  - EGF receptor trafficking: consequences for signaling and cancer.
AB  - The ligand-stimulated epidermal growth factor receptor (EGFR) has been
      extensively studied in the analysis of molecular mechanisms regulating endocytic
      traffic and the role of that traffic in signal transduction. Although such
      studies have largely focused on mitogenic signaling and dysregulated traffic in
      tumorigenesis, there is growing interest in the potential role of EGFR traffic in
      cell survival and the consequent response to cancer therapy. Here we review
      recent advances in our understanding of molecular mechanisms regulating ligand
      stimulated EGFR activation, internalization, and post-endocytic sorting. The role
      of EGFR overexpression/mutation and new modulators of EGFR traffic in cancer and
      the response to cancer therapeutics are also discussed. Finally, we speculate on
      the relationship between EGFR traffic and cell survival. 

PMID- 24295856
TI  - A new paradigm for health research funding.

PMID- 24295857
TI  - Differential mortality and the excess burden of end-stage renal disease among
      First Nations people with diabetes mellitus: a competing-risks analysis.
AB  - BACKGROUND: Diabetes-related end-stage renal disease disproportionately affects
      indigenous peoples. We explored the role of differential mortality in this
      disparity. METHODS: In this retrospective cohort study, we examined the competing
      risks of end-stage renal disease and death without end-stage renal disease among
      Saskatchewan adults with diabetes mellitus, both First Nations and non-First
      Nations, from 1980 to 2005. Using administrative databases of the Saskatchewan
      Ministry of Health, we developed Fine and Gray subdistribution hazards models and
      cumulative incidence functions. RESULTS: Of the 90 429 incident cases of
      diabetes, 8254 (8.9%) occurred among First Nations adults and 82,175 (90.9%)
      among non-First Nations adults. Mean age at the time that diabetes was diagnosed
      was 47.2 and 61.6 years, respectively (p<0.001). After adjustment for sex and age
      at the time of diabetes diagnosis, the risk of end-stage renal disease was 2.66
      times higher for First Nations than non-First Nations adults (95% confidence
      interval [CI] 2.24-3.16). Multivariable analysis with adjustment for sex showed a
      higher risk of death among First Nations adults, which declined with increasing
      age at the time of diabetes diagnosis. Cumulative incidence function curves
      stratified by age at the time of diabetes diagnosis showed greatest risk for end
      stage renal disease among those with onset of diabetes at younger ages and
      greatest risk of death among those with onset of diabetes at older ages.
      INTERPRETATION: Because they are typically younger when diabetes is diagnosed,
      First Nations adults with this condition are more likely than their non-First
      Nations counterparts to survive long enough for end-stage renal disease to
      develop. Differential mortality contributes substantially to ethnicity-based
      disparities in diabetes-related end-stage renal disease and possibly to chronic
      diabetes complications. Understanding the mechanisms underlying these disparities
      is vital in developing more effective prevention and management initiatives.

PMID- 24295860
TI  - Military urges provinces to improve access to health care for soldiers' families.

PMID- 24295859
TI  - A young woman with palpitations, goitre and low thyroid-stimulating hormone.

PMID- 24295861
TI  - Robotic surgical system under scrutiny.

PMID- 24295862
TI  - Human papillomavirus in head and neck cancer.

PMID- 24295863
TI  - "High-functioning addicts": intervening before trouble hits.

PMID- 24295864
TI  - Mental illness stigma in health care settings a barrier to care.

PMID- 24295866
TI  - Placing Aboriginal kidney disease in context.

PMID- 24295865
TI  - Association between First Nations ethnicity and progression to kidney failure by
      presence and severity of albuminuria.
AB  - BACKGROUND: Despite a low prevalence of chronic kidney disease (estimated
      glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people
      have high rates of kidney failure requiring chronic dialysis or kidney
      transplantation. We sought to examine whether the presence and severity of
      albuminuria contributes to the progression of chronic kidney disease to kidney
      failure among First Nations people. METHODS: We identified all adult residents of
      Alberta (age>=18 yr) for whom an outpatient serum creatinine measurement was
      available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using
      urine dipsticks and categorized results as normal (i.e., no albuminuria), mild,
      heavy or unmeasured. Our primary outcome was progression to kidney failure
      (defined as the need for chronic dialysis or kidney transplantation, or a
      sustained doubling of serum creatinine levels). We calculated rates of
      progression to kidney failure by First Nations status, by estimated GFR and by
      albuminuria category. We determined the relative hazard of progression to kidney
      failure for First Nations compared with non-First Nations participants by level
      of albuminuria and estimated GFR. RESULTS: Of the 1 816 824 participants we
      identified, 48 669 (2.7%) were First Nations. First Nations people were less
      likely to have normal albuminuria compared with non-First Nations people (38.7%
      v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold
      higher among First Nations people than among non-First Nations people, across all
      levels of albuminuria and estimated GFRs. Compared with non-First Nations people,
      First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had
      the highest risk of progression to kidney failure, with similar hazard ratios for
      those with normal and heavy albuminuria. INTERPRETATION: Albuminuria confers a
      similar risk of progression to kidney failure for First Nations and non-First
      Nations people.

PMID- 24295868
TI  - Developmental changes in cellular and humoral responses of the burying beetle
      Nicrophorus vespilloides (Coleoptera, Silphidae).
AB  - Necrophagous beetles of the genus Nicrophorus have developed various defence
      mechanisms that reduce the negative effects of adverse environmental conditions.
      However, many physiological and ecological aspects, including the functioning of
      the immune system in burying beetles, are still unknown. In this study, we show
      developmental changes in cellular and humoral responses of larvae, pupae, and
      adults of Nicrophorus vespilloides. We assessed changes in total haemocyte count,
      phenoloxidase activity, and phagocytic ability of haemocytes. We found that
      during larval development there is a progressive increase in humoral and cellular
      activities, and these responses are correlated with alterations of total
      haemocyte counts in the haemolymph. In the pupal stage, a sharp drop in the
      number of phagocytic haemocytes and an increase in phenoloxidase activity were
      observed. In adults, cellular and humoral responses remained at a lower level. It
      is probable that high lytic activity of anal and oral secretions produced by
      parents supports a lower response of the immune system in the initial phase of
      larval development. In the studied stages, we also observed differences in
      polymerisation of F-actin cytoskeleton of haemocytes, number of haemocytes
      forming filopodia, and filopodia length. These results suggest that the
      differences in immune responses during various stages of development of N.
      vespilloides are associated with a dynamically changing environment and different
      risks of infection. For the first time a detailed analysis of stage-specific
      alterations in immune system activity during development of the burying beetle is
      presented. 

PMID- 24295867
TI  - A halotyrosine antibody that detects increased protein modifications in asthma
      patients.
AB  - Airway inflammation has a pathophysiological role in asthma. Eosinophils, which
      are commonly increased in asthmatic airways, express eosinophil peroxidase and
      thereby produce hypobromite and bromotyrosine. Bromotyrosine is believed to be a
      specific marker for eosinophil activity, but developing an antibody against
      monobromotyrosine, the predominant brominated tyrosine residue found in vivo has
      proven difficult. We evaluated whether a 3-bromobenozoic acid hapten antigen
      produced antibodies that recognized halogenated tyrosine residues. Studies with
      small-molecule inhibitors or brominated or chlorinated protein suggested that a
      mouse monoclonal antibody (BTK-94C) selectively bound free and protein mono- and
      dibromotyrosine and, to a lesser degree, chlorotyrosine, and thus was designated
      a general halotyrosine antibody. We evaluated if this antibody had potential for
      characterizing human asthma using an enzyme-linked immunosorbent assay (ELISA)
      microarray platform to examine the halogenation of 23 proteins in three
      independent sets of sputum samples (52 samples total). In 15 healthy control or
      asthmatic subjects, ICAM, PDGF and RANTES had greater proportional amounts of
      halogenation in asthmatic subjects and the halogenation signal was associated
      with the severity of exercise-induced airway hyperresponsiveness. In 17 severe
      asthma patients treated with placebo or mepolizumab to suppress eosinophils, drug
      related decreases in halogenation were observed with p values ranging from 0.006
      to 0.11 for these 3 proteins. Analysis of 20 subjects that either had
      neutrophilic asthma or were healthy controls demonstrated a broad increase in
      halotyrosine (possibly chlorotyrosine) in neutrophilic asthmatics. Overall, these
      results suggest that an ELISA utilizing BTK-94C could prove useful for assessing
      airway inflammation in asthma patients. 

PMID- 24295869
TI  - HOPE for human liver grafts obtained from donors after cardiac death.
AB  - BACKGROUND & AIMS: Due to ethical rules in most countries, long ischemia times
      are unavoidable prior to organ procurement of donors without a heartbeat, which
      can cause early graft failure after liver transplantation or late biliary
      strictures. Hypothermic oxygenated machine perfusion, used prior to graft
      implantation, may rescue these high risk organs. METHODS: Eight patients with end
      stage liver diseases received human livers, obtained after controlled cardiac
      death (Maastricht category III), with a median donor warm ischemia time of 38
      min, followed by a standard cold flush and static storage at 4  degrees C.
      Hypothermic oxygenated perfusion (HOPE) was applied for 1-2h prior to
      implantation through the portal vein. The HOPE-perfusate was cooled at 10 
      degrees C and oxygenated (pO2 60 kPa) using an ECOPS device (Organ Assist(r)).
      Perfusion pressure was maintained below 3 mmHg. RESULTS: Each machine perfused
      liver graft disclosed excellent early function after transplantation. The release
      of liver enzymes and kidney function, as well as ICU and hospital stays were
      comparable or better than in matched liver grafts from brain death donors. No
      evidence of intrahepatic biliary complications could be documented within a
      median follow up of 8.5 months. CONCLUSIONS: This is the first report on cold
      machine perfusion of human liver grafts obtained after cardiac arrest and
      subsequent transplantation. Application of HOPE appears well tolerated, easy-to
      use, and protective against early and later injuries.

PMID- 24295870
TI  - Reply to: "To close the stable door before the horse has bolted".

PMID- 24295871
TI  - To close the stable door before the horse has bolted.

PMID- 24295872
TI  - Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin
      independent interference with the NTCP receptor.
AB  - BACKGROUND & AIMS: Chronic hepatitis B and hepatitis D are global health problems
      caused by the human hepatitis B and hepatitis D virus. The myristoylated preS1
      domain of the large envelope protein mediates specific binding to hepatocytes by
      sodium taurocholate co-transporting polypeptide (NTCP). NTCP is a bile salt
      transporter known to be inhibited by cyclosporin A. This study aimed to
      characterize the effect of cyclosporin A on HBV/HDV infection. METHODS: HepaRG
      cells, primary human hepatocytes, and susceptible NTCP-expressing hepatoma cell
      lines were applied for infection experiments. The mode of action of cyclosporin A
      was studied by comparing the effect of different inhibitors, cyclophilin A/B/C
      silenced cell lines as well as NTCP variants and mutants. Bile salt transporter
      and HBV receptor functions were investigated by taurocholate uptake and
      quantification of HBVpreS binding. RESULTS: Cyclosporin A inhibited hepatitis B
      and D virus infections during and--less pronounced--prior to virus inoculation.
      Binding of HBVpreS to NTCP was blocked by cyclosporin A concentrations at 8 MUM.
      An NTCP variant deficient in HBVpreS binding but competent for bile salt
      transport showed resistance to cyclosporin A. Silencing of cyclophilins A/B/C did
      not abrogate transporter and receptor inhibition. In contrast, tacrolimus, a
      cyclophilin-independent calcineurin inhibitor, was inactive. CONCLUSIONS: HBV and
      HDV entry via sodium taurocholate co-transporting polypeptide is inhibited by
      cyclosporin A. The interaction between the drug and the viral receptor is direct
      and overlaps with a functional binding site of the preS1 domain, which mediates
      viral entry.

PMID- 24295873
TI  - Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF
      monotherapy in adefovir-experienced chronic hepatitis B patients.
AB  - BACKGROUND & AIMS: Suboptimal virologic response to nucleos(t)ide analogs may
      represent a significant risk factor for resistance development in patients with
      chronic hepatitis B virus infection; treatment options have not been well
      studied. We evaluated long-term efficacy and safety of tenofovir alone and in
      combination with emtricitabine in a prospective, placebo-controlled trial in
      patients who remained viremic on adefovir therapy. METHODS: Hepatitis B e antigen
      positive and -negative patients with hepatitis B virus DNA ? 1000 copies/ml
      despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or
      emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ? 400
      copies/ml (? 69IU/ml) at or after week 24 could switch to open-label
      emtricitabine/tenofovir. RESULTS: Overall, 90/105 (86%) patients (46/53 tenofovir
      and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including
      74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who
      completed the study on their initial randomized treatment. Long-term viral
      suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in
      84% and 82% of patients receiving either emtricitabine/tenofovir combination or
      tenofovir monotherapy, respectively (non-completer equal to failure analysis).
      Baseline viral load as well as the presence of lamivudine and/or adefovir
      resistance-associated mutations at baseline had no impact on long-term treatment
      response. No resistance to tenofovir was observed through 168 weeks. Both
      treatments had a favorable safety profile. CONCLUSIONS: Tenofovir monotherapy is
      as effective as emtricitabine/tenofovir combination therapy in maintaining long
      term viral suppression in patients with a suboptimal response to adefovir, and is
      well tolerated in this population.

PMID- 24295874
TI  - Autoimmune hepatitis on the rise.

PMID- 24295875
TI  - Reply to: "To close the stable door before the horse has bolted".

PMID- 24295877
TI  - Comparison of back pain prognostic risk stratification item sets.
AB  - Back pain outcomes may be improved and costs lowered through risk-stratified
      care, but relative performance of alternative item sets for predicting back pain
      outcomes has not been well characterized. We compared alternative prognostic item
      sets based on STarT Back and Chronic Pain Risk screeners in a cohort of patients
      initiating primary care for back pain. The STarT Back item set was brief and
      relied on binary responses, whereas the Chronic Pain Risk item set employed
      scaled responses and assessed pain persistence and diffuse pain. Patients (N =
      571) were assessed soon after their initial visit and 502 (88%) were reassessed 4
      months later. Items sets based on STarT Back and Chronic Pain Risk prognostic
      screeners, as well as a combination of items from both, were used to predict
      Chronic Pain Grade II-IV back pain at 4 months. The area under the receiver
      operating characteristic curve estimates (95% confidence intervals) were .79 (.74
      .83) for items based on the STarT Back, .80 (.75-.83) for items based on Chronic
      Pain Risk, and .81 (.77-.85) for a composite item set. Differences in prediction
      were modest. Items from 2 prognostic screeners, and both combined, achieved
      acceptable and similar prediction of unfavorable back pain outcomes. PERSPECTIVE:
      Given comparable predictive validity, choice among prognostic item sets should be
      based on clinical relevance, number of items, ease of administration, and item
      simplicity.

PMID- 24295876
TI  - The association between negative affect and prescription opioid misuse in
      patients with chronic pain: the mediating role of opioid craving.
AB  - Over the past decade, considerable research has accumulated showing that chronic
      pain patients experiencing high levels of negative affect (NA) are at increased
      risk for prescription opioid misuse. The primary objective of the present study
      was to examine the factors that underlie the association between NA and
      prescription opioid misuse among patients with chronic pain. In this study, 82
      patients with chronic musculoskeletal pain being prescribed opioid medication
      completed the Current Opioid Misuse Measure, a well-validated self-report
      questionnaire designed to assess prescription opioid misuse. Patients were also
      asked to complete self-report measures of pain intensity, NA, and opioid craving.
      A bootstrapped multiple mediation analysis was used to examine the mediating role
      of patients' pain intensity and opioid craving in the association between NA and
      prescription opioid misuse. Consistent with previous research, we found a
      significant association between NA and prescription opioid misuse. Interestingly,
      results revealed that opioid craving, but not pain intensity, mediated the
      association between NA and opioid misuse. The Discussion addresses the potential
      psychological and neurobiological factors that might contribute to the
      interrelationships among NA, opioid craving, and prescription opioid misuse in
      patients with pain. The clinical implications of our findings are also discussed.
      PERSPECTIVE: Our study provides new insights into the factors that underlie the
      association between negative affect and prescription opioid misuse in patients
      with chronic pain. Our findings could have important clinical implications,
      particularly for patients being prescribed opioid medication, and for reducing
      rates of opioid misuse in patients with pain.

PMID- 24295880
TI  - Diagnosis and treatment of a symptomatic primary thoracic aortic tumor:
      endovascular exclusion to prevent recurrent embolization.
AB  - Intraluminal aortic malignant masses are extremely rare. Clinical symptoms of
      these tumors include locally occlusive aortic disease, peripheral emboli, or
      mesenteric emboli. Eventually, general symptoms, such as fatigue, weight loss, or
      fever, will occur. Nevertheless, the diagnosis is most often made after surgery
      or autopsy, when histologic data can be examined. Few cases of intraaortic masses
      treated endovascularly have been reported, most of them related to intraluminal
      blood clot formation. We present a case of intraaortic malignant tumor formation
      with distal embolization to the legs, in which the diagnosis of malignant disease
      was reached after analysis of the material obtained during embolectomy.
      Endovascular exclusion was performed as a transient treatment to avoid new
      embolic events. 

PMID- 24295878
TI  - Cobalt(III)hexaammine-dependent photocrosslinks in the hairpin ribozyme.
AB  - We have utilized the hairpin ribozyme, an RNA enzyme whose structure has been
      solved by high-resolution methods, to develop a new tool for mapping nucleobase
      stacking interactions and potential metal-binding sites in RNA molecules. This
      tool involves the photoactivation of a specifically bound cobalt(III)hexaammine
      molecule at wavelengths corresponding to excitation of the metal ion complex
      only; no base excitation is involved. The photoexcitation initiates a process
      which strongly promotes the formation of a novel covalent bond or crosslink
      between one base (termed the "first base"), which is close in space to the
      excited cobalt(III)hexaammine complex, and another base upon which the first base
      is closely stacked. These crosslinked species can be isolated and sequenced;
      their activities can be analyzed to ensure that the crosslinked structures
      represent an active conformation of the molecule. We have shown that, as in
      electron transfer in DNA, several criteria must be met to result in the
      successful formation of these crosslinks. These include the appropriate oxidation
      potential of the first donor base, the stacking and close interaction of the two
      donor bases involved in the crosslink, and the binding of a specific
      cobalt(III)hexaammine molecule to the first donor base. Additionally, we have
      determined that this crosslinking is pH-sensitive, although the cause of this
      sensitivity remains unknown. This tool has proven useful in the past for the
      analysis of the hairpin ribozyme folded structure, and has been applied to
      identify potential metal-binding sites on the hairpin and extended hammerhead
      ribozymes.

PMID- 24295879
TI  - Implementation of the NHLBI integrated guidelines for cardiovascular health and
      risk reduction in children and adolescents: rationale and study design for young
      hearts, strong starts, a cluster-randomized trial targeting body mass index,
      blood pressure, and tobacco.
AB  - BACKGROUND: Cardiovascular disease (CVD) and the underlying atherosclerosis begin
      in childhood, and their presence and intensity are related to known
      cardiovascular disease risk factors. Attention to risk factor control in
      childhood has the potential to reduce subsequent risk of CVD. OBJECTIVE: The
      Young Hearts Strong Starts Study was designed to test strategies facilitating
      adoption of the National, Heart, Lung and Blood Institute supported Integrated
      Guidelines for Cardiovascular Health and Risk Reduction in Children and
      Adolescents. This study compares guideline-based quality measures for body mass
      index, blood pressure, and tobacco using two strategies: a multifaceted, practice
      directed intervention versus standard dissemination. STUDY DESIGN: Two primary
      care research networks recruited practices and provided support for the
      intervention and outcome evaluations. Individual practices were randomly assigned
      to the intervention or control groups using a cluster randomized design based on
      network affiliation, number of clinicians per practice, urban versus nonurban
      location, and practice type. The units of observation are individual children
      because measure adherence is abstracted from individual patient's medical
      records. The units of randomization are physician practices. This results in a
      multilevel design in which patients are nested within practices. The intervention
      practices received toolkits and supported guideline implementation including
      academic detailing, an ongoing e-learning group. This project is aligned with the
      American Board of Pediatrics Maintenance of Certification requirements including
      monthly physician self-abstraction, webinars, and other elements of the trial.
      SIGNIFICANCE: This trial will provide an opportunity to demonstrate tools and
      strategies to enhance CV prevention in children by guideline-based interventions.

PMID- 24295882
TI  - Endovascular repair of a paraanastomotic aneurysm with inverted limb infrarenal
      bifurcated graft.
AB  - A typical complication after conventional aortic prosthetic reconstruction is
      paraanastomotic aneurysm formation. Endovascular exclusion of paraanastomotic
      aneurysms has been shown to be a viable alternative to open surgical repair and
      to greatly reduce morbidity and mortality rates. We present a case report of
      asymptomatic proximal anastomotic pseudoaneurysm, measuring 4.5 cm in diameter,
      that was successfully treated by endovascular repair with a custom-made inverted
      limb infrarenal bifurcated graft. 

PMID- 24295881
TI  - Bilateral abnormal origin of the anterior branches of the external carotid
      artery.
AB  - BACKGROUND: Description of a rare variation is provided alongside with a review
      of the literature with special references to anatomic, embryologic, and clinical
      issues it may create. METHODS: This was a cadaveric dissection conducted during a
      pregraduate anatomy course that is accompanied by short review of the literature
      and critical appraisal. RESULTS: During dissection of the neck region of a male
      cadaver, the superior thyroid artery occurred from the common carotid artery
      bilaterally and the lingual artery occurred from the carotid bifurcation on the
      left side. CONCLUSIONS: Superior thyroid artery originating from common carotid
      artery or carotid bifurcation is a common variation, but the lingual artery
      originating from the common carotid artery or carotid bifurcation is very rare
      (<1%). Its existence can have a significant impact on treatment success and
      potentially lead to errors during interventions at the neck region. A high level
      of suspicion is required.

PMID- 24295883
TI  - Paraplegia after aortic and superior mesenteric artery stenting for occlusive
      disease.
AB  - Paraplegia after endovascular therapy for aortic and visceral artery occlusive
      disease is an extremely uncommon occurrence. Two cases of paraplegia after
      placement of an aortic covered stent for infrarenal aortic stenosis and a
      superior mesenteric artery stent for chronic visceral ischemia are presented. In
      both patients, embolization of the arterial supply to the spinal cord was the
      presumed cause. One patient had a slight recovery after intense physical therapy
      and rehabilitation. The second patient did not have any recovery from her
      paraplegia. 

PMID- 24295884
TI  - Simultaneous transcervical angioplasty and stenting of innominate and right
      internal carotid arteries.
AB  - Severe stenosis of both the internal carotid and the innominate arteries is a
      rare condition. Hybrid procedures combining carotid endarterectomy and retrograde
      endovascular innominate angioplasty have been introduced to reduce the
      complications of open surgery. The recently reported good results of carotid
      angioplasty and stenting have encouraged us to perform simultaneous transcervical
      angioplasties and stenting of both arteries in a symptomatic 64-year-old woman.
      The procedure was successful and without complications and there have been no
      symptoms or restenosis in the 18-month follow-up period. Carrying out additional
      procedures of this will be necessary to reach wider conclusions. 

PMID- 24295886
TI  - Seasonal plasticity of the pituitary pars intermedia of the one-humped camel
      (Camelus dromedarius).
AB  - The pituitary pars intermedia of Camelus dromedarius is well developed and
      completely surrounds the pars nervosa. Two major groups of cells are present:
      endocrine (ec) and glial-like cells (glc). The ec group is composed of three
      morphologically distinct cell types. Type I, or polyhedral light cells (LC-I) and
      type II, or polyhedral dark cells (DC-II), have secretory granules of
      heterogeneous electron density whose size ranges from 170 to 300nm. Type III
      cells are elongated with homogeneous electron-dense secretory granules of 80
      200nm. The glc make up an organized network, form follicles in the centrolobular
      zones and are positive for vimentin and S-100beta immunolabelling. The nerve
      fibres penetrating the lobe are numerous, and can be classified into two types
      according to the membrane bound vesicles found in their endings (ne).
      Ultrastructural quantitative analysis revealed significant variations in PI
      elements between winter and summer seasons (F=8.014, p=0.006). DC-II cells
      characterized by developed biosynthetic machinery and a large pool of secretory
      granules storage are increased with the ne in winter. However, LC-I cells showing
      frequent cytoplasmic degranulation are predominant with glc in summer. Thus,
      important cellular remodelling occurs in the dromedary PI that may depend upon,
      or perhaps anticipate, external living conditions. 

PMID- 24295885
TI  - Diagnosis and whole body screening using blood pool scintigraphy for evaluating
      congenital vascular malformations.
AB  - BACKGROUND: Because magnetic resonance imaging and angiography are inappropriate
      for whole-body screening because of high cost or invasiveness, we investigated
      the potential of whole-body blood pool scintigraphy (WBBPS) as a screening and
      diagnostic tool for congenital vascular malformations (CVMs). METHODS: The
      subjects of the study were 137 patients (mean age: 20 +/- 16 years; range: 0.3-68
      years) with suspected CVM. Whole-body anterior and posterior images were acquired
      twenty minutes after injection of 760 MBq (99m)Tc-labeled red blood cells
      (pediatric dose: 13 MBq/kg). The final diagnosis was determined by clinical
      findings, magnetic resonance imaging, angiography, Doppler sonography, and
      lymphoscintigraphy. RESULTS: Of these patients, 124 had venous malformations, and
      13 had lymphatic malformations. WBBPS successfully detected abnormal blood
      pooling lesions in 96.8% (120/124) of the patients with venous malformations.
      None of the patients with lymphatic malformation showed abnormal uptake on WBBPS.
      In addition, WBBPS detected 41 additional abnormal vascular lesions that were not
      found during initial clinical evaluation in 16.9% (21/124) of the patients with
      venous malformations. CONCLUSION: WBBPS is a valuable diagnostic and screening
      modality for the initial evaluation of CVM because of its high characterizing
      accuracy of 97.1% and the ability to image the whole body.

PMID- 24295887
TI  - The genetic structure of the A mating-type locus of Lentinula edodes.
AB  - The Shiitake mushroom, Lentinula edodes (Berk.) Pegler is a tetrapolar
      basidiomycete with two unlinked mating-type loci, commonly called the A and B
      loci. Identifying the mating-types in shiitake is important for enhancing the
      breeding and cultivation of this economically-important edible mushroom. Here, we
      identified the A mating-type locus from the first draft genome sequence of L.
      edodes and characterized multiple alleles from different monokaryotic strains.
      Two intron-length polymorphism markers were developed to facilitate rapid
      molecular determination of A mating-type. L. edodes sequences were compared with
      those of known tetrapolar and bipolar basidiomycete species. The A mating-type
      genes are conserved at the homeodomain region across the order Agaricales.
      However, we observed unique genomic organization of the locus in L. edodes which
      exhibits atypical gene order and multiple repetitive elements around its A locus.
      To our knowledge, this is the first known exception among Homobasidiomycetes, in
      which the mitochondrial intermediate peptidase (mip) gene is not closely linked
      to A locus. 

PMID- 24295888
TI  - Conservation genetics of endangered medicinal plant Commiphora wightii in Indian
      Thar Desert.
AB  - To ascertain the conservation priorities and strategies for Commiphora wightii,
      an endangered medicinal plant of Indian Thar Desert, genetic diversity was
      estimated within and among different populations. The total of 155 amplification
      products were scored using ten each of RAPD and ISSR primers, exhibiting an
      overall 86.72% polymorphism across 45 individuals representing eight populations.
      The cumulative data of two markers were used to compute pair-wise distances. The
      Neighbor-Joining tree revealed high genetic differentiation among populations
      except Kiradu population. Nei's gene diversity (h) ranged between 0.082 and 0.193
      with total diversity at species level is 0.294. Shannon's information index (I)
      ranged between 0.118 and 0.275 with an overall diversity of 0.439. Analysis of
      molecular variance showed more diversity among population level (56.65%) than at
      within population level (43.35%). The low gene flow value (Nm=0.349) and high
      coefficient of genetic differentiation (GST=0.589) and high fixation index
      (FST=0.566) demonstrated elevated genetic differentiation among the population
      and can be predicted that these populations are not in Hardy-Weinberg
      proportions. Principal Co-ordinate Analysis confirms that Akal population has
      become phylogenetically more distinct and less diverse than the rest of the
      samples. Mantel's test revealed no correlation between genetic and geographical
      distances of populations (R(2)=0.122). Overall highest diversity was observed in
      the population of Machiya Safari Park and Kiradu, while lowest in Akal
      population, later may constitute an evolutionary significant unit, having merit
      for special management. 

PMID- 24295889
TI  - Identification of a deletion in the NDUFS4 gene using array-comparative genomic
      hybridization in a patient with suspected mitochondrial respiratory disease.
AB  - We evaluated a patient, born after a normal 38-week pregnancy, with psychomotor
      retardation, poor coordination of ocular movements, recurrent vomiting and severe
      lactic acidosis. The patient was admitted to hospital at 2 months of age because
      of a mitochondrial-like syndrome and died at the age of 4.5 months. Array
      comparative genomic hybridization (a-CGH) analysis revealed a homozygous deletion
      in 5q11.2 involving NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18 kDa (NADH
      coenzyme Q reductase; NDUFS4). Both parents were heterozygous for the mutation.
      The array revealed a deletion of ~32kb that includes exon 2 of NDUFS4
      subsequently confirmed by real time-PCR and multiplex PCR. NDUFS4 was previously
      correlated to Leigh syndrome since mutations in this gene block the assembly of
      complex I. This result demonstrates the relevance of a-CGH screening in patients
      affected by metabolic disorders of unknown etiology.

PMID- 24295890
TI  - Genetic analysis of the TBX1 gene promoter in indirect inguinal hernia.
AB  - Inguinal hernia is a common disease, most cases of which are indirect inguinal
      hernia (IIH). Genetic factors play an important role for inguinal hernia.
      Increased incidences of inguinal hernia have been reported in patients with
      22q11.2 microdeletion syndrome, which is mainly caused by TBX1 gene mutations.
      Thus, we hypothesized that altered TBX1 gene expression may contribute to IIH
      development. In this study, the human TBX1 gene promoter was genetically analyzed
      in children with IIH (n=100) and ethnic-matched controls (n=167). Functions of
      DNA sequence variants (DSVs) within the TBX1 gene promoter were examined in
      cultured human fibroblast cells. The results showed that two heterozygous DSVs
      were found, both of which were single nucleotide polymorphisms. One DSV, g.4248
      C>T (rs41298629), was identified in a 2-year-old boy with right-sided IIH, but
      not in all controls, which significantly decreased TBX1 gene promoter activity.
      Another DSV, g.4199 C>T (rs41260844), was found in both IIH patients and controls
      with similar frequencies (P>0.05), which did not affect TBX1 gene promoter
      activity. Collectively, our data suggested that the DSV within the TBX1 gene
      promoter may change TBX1 level, contributing to IIH development as a rare risk
      factor. Underlying molecular mechanisms need to be established. 

PMID- 24295891
TI  - Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility
      to vitiligo.
AB  - BACKGROUND: Some studies suggested that Glutathione S-transferases
      M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo.
      AIMS: The purpose of this study is to further evaluate the association between
      GSTM1/T1 null polymorphisms and the susceptibility to vitiligo. METHODS: We
      carried out a retrieval of studies in the databases. Odds ratios (OR) and 95%
      confidence intervals (95% CIs) were used to assess the strength of this
      association. We analyzed the data using Stata 11.0. RESULTS: Six case-control
      studies including 1358 cases and 1673 controls were included in this meta
      analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was
      associated with vitiligo (GSTM1:OR=1.59, 95% CI: 1.21-2.08, P=0.001; GSTT1:
      OR=1.30, 95% CI: 1.12-1.51, P=0.001). In the subgroup analysis, the GSTM1 null
      polymorphism might be a genetic risk factor to vitiligo in East Asian (OR=1.71,
      95% CI: 1.12-2.63, P=0.014) but not in the Mediterranean, however individuals
      with the GSTT1 null polymorphism in the Mediterranean (OR=1.76, 95% CI: 1.15
      2.71, P=0.010) but not in East Asian have a greater predisposition to vitiligo.
      In addition there was also a significant trend toward an association with the
      combination of the GSTM1 null and GSTT1 null in either East Asians or
      Mediterraneans. CONCLUSION: The GSTM1/T1 null polymorphisms may be associated
      with vitiligo. More studies are needed to confirm this conclusion.

PMID- 24295893
TI  - Cervicothoracic junction instability after cervical fusion.

PMID- 24295892
TI  - Current status and future challenges for controlling malaria with the sterile
      insect technique: technical and social perspectives.
AB  - The intolerable burden of malaria, when faced with high levels of drug
      resistance, increasing insecticide resistance and meagre resources at the
      national level, remains a great public health challenge to governments and the
      research/control community. Efficient control methods against the vectors of
      malaria are desperately needed. Control strategies for malaria that integrate the
      transfer of sterile sperm by released males to wild virgin females with other
      control tactics are currently being developed, and optimised mass-rearing,
      irradiation and release techniques are being validated in several field sites.
      However, the success of this strategy as part of wider pest control or health
      management programmes strongly depends on gaining public understanding and
      acceptance. Here we attempt to review what progress has been made and the
      remaining challenges surrounding the use of the sterile insect technique against
      malaria from technical and social perspectives. 

PMID- 24295894
TI  - Cervical spondylotic myelopathy with subacute combined degeneration.

PMID- 24295895
TI  - Use of oxcarbazepine for treatment of refractory status epilepticus.
AB  - PURPOSE: Oxcarbazepine (OXC) is an effective anticonvulsant used for treatment of
      partial and secondarily generalized seizures. However, there is almost no data
      regarding its effectiveness and tolerability when used for treatment of status
      epilepticus (SE). METHODS: We retrospectively identified all patients who
      received OXC for treatment of SE in our hospital between July 2008 and December
      2010 in our hospital and analyzed all available data. RESULTS: We identified 13
      patients (median age 79 years) who were treated with OXC for refractory SE after
      failure of first- and second-line therapy in our institution. In the majority of
      patients, etiology was remote symptomatic (10/13), and semiology was
      nonconvulsive (10/13). OXC was initiated as third or later agent in almost all
      patients after median latency of 81 h with a median maximum daily dose of 1800
      mg. OXC was the last drug before SE cessation in 8/13 patients. Relevant
      hyponatriemia <125 mmol/l was seen in 3 patients. CONCLUSION: OXC may be an
      effective alternative in refractory SE, but patients need to be monitored closely
      for hyponatriemia. PRACTICE IMPLICATIONS: OXC could be used for refractory SE
      under close electrolyte monitoring when standard agents fail or are unsuitable.

PMID- 24295896
TI  - Lateral step initiation behavior in older adults.
AB  - Older adults have varied postural responses during induced and voluntary lateral
      stepping. The purpose of the research was to quantify the occurrence of different
      stepping strategies during lateral step initiation in older adults and to relate
      the stepping responses to retrospective history of falls. Seventy community
      ambulating older adults (mean age 76 y, range 70-94 y) performed voluntary
      lateral steps as quickly as possible to the right or left in response to a visual
      cue, in a blocked design. Vertical ground reaction forces were measured using a
      forceplate, and the number and latency of postural adjustments were quantified.
      Subjects were assigned to groups based on their stepping strategy. The frequency
      of trials with one or two postural adjustments was compared with data from 20
      younger adults (mean age 38 y, range 21-58 y). Logistic regression was used to
      relate presence of a fall in the previous year with the number and latency of
      postural adjustments. In comparison with younger adults, who almost always
      demonstrated one postural adjustment when stepping laterally, older adults
      constituted a continuous distribution in the percentage of step trials made with
      one postural adjustment (from 0% to 100% of trials). Latencies of the initial
      postural adjustment and foot liftoff varied depending on the number of postural
      adjustments made. A history of falls was associated a larger percentage of two
      postural adjustments, and a longer latency of foot liftoff. In conclusion, the
      number and latency of postural adjustments made during voluntary lateral stepping
      provides additional evidence that lateral control of posture may be a critical
      indicator of aging. 

PMID- 24295897
TI  - Muscle function in adults with congenital heart disease.
AB  - BACKGROUND: The aim was to assess muscle function in a sample of Swedish adult
      men and women with congenital heart disease (ACHD) and to compare the results
      with published reference values in healthy adults. METHODS AND RESULTS: From
      April 2009 to December 2010, 762 adult outpatients were assessed for their
      suitability and individual need for tests of physical fitness. The patients
      performed five muscle function tests, two isotonic tests and three isometric
      tests. Of the 762 patients, 315 (41.3%) patients performed the tests. Patients
      with ACHD had lower isotonic muscle function compared to healthy reference
      values. In the heel lift test, men with ACHD performed at 63% and women at 58% of
      the healthy reference values and in the shoulder flexion test the corresponding
      performance level was 60% for men with ACHD and 85% for the women. Multiple
      regression analyses showed that NYHA class II-IV was a significant predictor for
      a lower isotonic muscle function i.e. heel lift in women (p<0.001) and men
      (p=0.05) and in shoulder flexion (p<0.001) in women, as well as in isometric knee
      extension (p=0.04) and isometric shoulder abduction (p<0.001) in women.
      CONCLUSION: This is the first report of muscle function in a broad and unselected
      group of patients with ACHD. Our data shows that patients with ACHD have lower
      isotonic muscle function. The impacts of low muscle function in activities of
      daily living and the question of whether muscle function could be improved with
      exercise training need further investigation.

PMID- 24295898
TI  - Genetic analysis in a family affected by sick sinus syndrome may reduce the
      sudden death risk in a young aspiring competitive athlete.

PMID- 24295900
TI  - Model fit to experimental data for foam-assisted deep vadose zone remediation.
AB  - This study investigates how a foam model, developed in Roostapour and Kam [1],
      can be applied to make a fit to a set of existing laboratory flow experiments in
      an application relevant to deep vadose zone remediation. This study reveals a few
      important insights regarding foam-assisted deep vadose zone remediation: (i) the
      mathematical framework established for foam modeling can fit typical flow
      experiments matching wave velocities, saturation history, and pressure responses;
      (ii) the set of input parameters may not be unique for the fit, and therefore
      conducting experiments to measure basic model parameters related to relative
      permeability, initial and residual saturations, surfactant adsorption and so on
      should not be overlooked; and (iii) gas compressibility plays an important role
      for data analysis, thus should be handled carefully in laboratory flow
      experiments. Foam kinetics, causing foam texture to reach its steady-state value
      slowly, may impose additional complications. 

PMID- 24295899
TI  - PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in
      cancer.
AB  - Whereas moderately increased cellular oxidative stress is supportive for
      cancerous growth of cells, excessive levels of reactive oxygen species (ROS) are
      detrimental to their growth and survival. We demonstrated that high ROS levels,
      via increased oxidized glutathione (GSSG), induce isoform-specific S
      glutathionylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
      (PFKFB3) at residue Cys206, which is located near the entrance to the 6
      phosphofructo-2-kinase catalytic pocket. Upon this ROS-dependent, reversible,
      covalent modification, a marked decrease in its catalytic ability to synthesize
      fructose-2,6-bisphosphate (Fru-2,6-P2), the key glycolysis allosteric activator,
      was observed. This event was coupled to a decrease in glycolytic flux and an
      increase in glucose metabolic flux into the pentose phosphate pathway. This
      shift, in turn, caused an increase in reduced glutathione (GSH) and, ultimately,
      resulted in ROS detoxification inside HeLa cells. The ability of PFKFB3 to
      control the Fru-2,6-P2 levels in an ROS-dependent manner allows the PFKFB3
      expressing cancer cells to continue energy metabolism with a reduced risk of
      excessive oxidative stress and, thereby, to support their cell survival and
      proliferation. This study provides a new insight into the roles of PFKFB3 as
      switch that senses and controls redox homeostasis in cancer in addition to its
      role in cancer glycolysis.

PMID- 24295901
TI  - Occurrence of classic and emerging halogenated flame retardants in sediment and
      sludge from Ebro and Llobregat river basins (Spain).
AB  - Classic (polybromodiphenyl ethers, PBDEs) and emerging halogenated flame
      retardants such as hexabromobenzene (HBB), pentabromoetilbenzene (PBEB),
      decabromodiphenyl ethane (DBDPE), Dechlorane 602 (Dec 602), Dechlorane 603 (Dec
      603), Dechlorane 604 (Dec 604) and Dechlorane plus (DP) were analyzed in 33
      sediments and 7 sludges from two Iberian river basins, Ebro and Llobregat. In
      sediment samples, PBDE levels ranged between nd and 44.3ng/g dw with BDE-209
      being the most abundant congener. Levels of DBDPE and halogenated norbornenes
      ranged between nd and 31.5ng/g dw and between nq and 3.74ng/g dw, respectively.
      This is the first study to report halogenated norbornene levels in sediment
      samples from Spain. PBDE, DBDPE and halogenated norbornene levels in sludge
      ranged from 13 to 340, nq to 124 and 2.7 to 19ng/g dw, respectively. HBB and PBEB
      were not detected in any sample. Levels of classic and emerging HFRs were
      compared. Our results suggest that DBDPE is the most frequently used compound to
      replace BDE-209, whereas the use of halogenated norbornenes is still low. 

PMID- 24295902
TI  - Wild gudgeons (Gobio gobio) from French rivers are contaminated by microplastics:
      preliminary study and first evidence.
AB  - Marine ecosystem contamination by microplastics is extensively documented.
      However few data is available on the contamination of continental water bodies
      and associated fauna. The aim of this study was to address the occurrence of
      microplastics in digestive tract of gudgeons (Gobio gobio) from French rivers.
      These investigations confirm that continental fish ingested microplastics while
      12% of collected fish are contaminated by these small particles. Further works
      are needed to evaluate the occurence of this contamination. 

PMID- 24295903
TI  - Interpreting systematic reviews: looking beyond the all too familiar conclusion.

PMID- 24295905
TI  - Reflectance infrared spectroscopy for in-line monitoring of nicotine during a
      coating process for an oral thin film.
AB  - A process analytical method using reflectance infrared spectrometry was developed
      for the in-line monitoring of the amount of the active pharmaceutical ingredient
      (API) nicotine during a coating process for an oral thin film (OTF). In-line
      measurements were made using a reflectance infrared (RI) sensor positioned after
      the last drying zone of the coating line. Real-time spectra from the coating
      process were used for modelling the nicotine content. Partial least squares
      (PLS1) calibration models with different data pre-treatments were generated. The
      calibration model with the most comparable standard error of calibration (SEC)
      and the standard error of cross validation (SECV) was selected for an external
      validation run on the production coating line with an independent laminate. Good
      correlations could be obtained between values estimated from the reflectance
      infrared data and the reference HPLC test method, respectively. With in-line
      measurements it was possible to allow real-time adjustments during the production
      process to keep product specifications within predefined limits hence avoiding
      loss of material and batch. 

PMID- 24295906
TI  - Determination of bile acids by hollow fibre liquid-phase microextraction coupled
      with gas chromatography.
AB  - A method based on hollow-fibre liquid phase microextraction combined with gas
      chromatography was developed for determination of specific bile acids in caecal
      materials of rats. Nine unconjugated bile acids, including the primary bile acids
      (cholic acid, chenodeoxycholic acid and alpha-muricholic acid) and the secondary
      bile acids (lithocholic acid, deoxycholic acid, ursodeoxycholic acid,
      hyodeoxycholic acid, beta-muricholic acid and omega-muricholic acid) were
      quantified. Extraction conditions were evaluated, including: sample pH, type of
      organic solvent and amount of caecal material to be extracted. To compensate for
      sample matrix effects during extraction the method of standard addition was
      applied. The satisfactory linearity (r(2)>0.9840), high recovery (84.2-108.7%)
      and good intra-assay (6.3-10.6%) and inter-assay (6.9-11.1%) precision
      illustrated the good performance of the present method. The method is rapid,
      simple and capable of detecting and determining bile acids with limit of
      detection (LOD) ranged from 0.002 to 0.067MUg/mL and limits of quantification
      (LOQ) varied from 0.006 to 0.224MUg/mL. The results indicated that the
      concentration of some secondary bile acids, which usually are associated with
      health problems, were lower in rats fed with fermentable dietary fibre compared
      with a fibre free control diet, while the concentration of primary bile acids,
      usually connected with positive health effects, were higher in rats fed with
      diets containing dietary fibre. Of the dietary fibres, guar gum and to some
      extent the mixture of pectin+guar gum had the most positive effects. Thus, it was
      concluded that the composition of bile acids can be affected by the type of diet.

PMID- 24295907
TI  - Simultaneous determination of five bioactive secolignans in rat plasma by LC
      MS/MS for pharmacokinetic studies following oral administration of Peperomia
      dindygulensis Miq. extract.
AB  - A rapid and sensitive ultra fast performance liquid chromatography-tandem mass
      spectrometry method was developed for the simultaneous determination of five
      bioactive secolignans in Peperomia dindygulensis extract, including peperomin A,
      peperomin B, peperomin C, 4"-hydroxypeperomin B and 4"-hydroxypeperomin C in rat
      plasma. Arctigenin was used as the internal standard. The separation was
      performed on an InnovationTM Polar-RP C18 column by a gradient elution within a
      runtime of 7min. The mobile phase consisted of A (methanol) and B (0.1% formic
      acid in water) at a flow rate of 0.4mL/min. The detection was accomplished by
      using positive ion TurboIonSpray ionization in multiple reaction monitoring mode.
      The method was linear for all analytes over investigated range with all
      correlation coefficients greater than 0.9972. The lower limits of quantification
      were 1.1ng/mL for peperomin A, 1.24ng/mL for peperomin B, 1.02ng/mL for peperomin
      C, 1.91ng/mL for 4"-hydroxypeperomin B and 1.27ng/mL for 4"-hydroxypeperomin C.
      The intra- and inter-day precision (RSD%) was within 15% and the accuracy (RE%)
      ranged from -11.7% to 10.3%. This simple and sensitive method was fully validated
      and successfully applied to the pharmacokinetic study of peperomin A, peperomin
      B, peperomin C, 4"-hydroxypeperomin B and 4"-hydroxypeperomin C in rat plasma
      after oral administration of P. dindygulensis extract. 

PMID- 24295908
TI  - A sensitive UPLC-MS/MS method for simultaneous determination of eleven bioactive
      components of Tong-Xie-Yao-Fang decoction in rat biological matrices.
AB  - There is a growing concern for the sensitive quantification of multiple
      components using advanced data acquisition method in herbal medicines (HMs). An
      improved and rugged UPLC-MS/MS method has been developed and validated for
      sensitive and rapid determination of multiply analytes from Tong-Xie-Yao-Fang
      (TXYF) decoction in three biological matrices (plasma/brain tissue/urine) using
      geniposide and formononetin as internal standards. After solid-phase extraction,
      chromatographic separation was performed on a C18 column using gradient elution.
      Quantifier and qualifier transitions were monitored using novel Triggered Dynamic
      multiple reaction monitoring (TdMRM) in the positive ionization mode. A
      significant peak symmetry and sensitivity improvement in the TdMRM mode was
      achieved as compared to conventional MRM. The reproducibility (RSD%) was <=7.9%
      by applying TdMRM transition while the values were 6.8-20.6% for MRM. Excellent
      linear calibration curves were obtained under TdMRM transitions over the tested
      concentration ranges. Intra- and inter-day precisions (RSD%) were <=14.2% and
      accuracies (RE%) ranged from -9.6% to 10.6%. The validation data of specificity,
      carryover, recovery, matrix effect and stability were within the required limits.
      The method was effectively applied to simultaneously detect and quantify 1
      lactone, 2 monoterpene glucosides, 1 alkaloid, 5 flavonoids and 2 chromones in
      plasma, brain tissue and urine after oral administration of TXYF decoction. In
      conclusion, this new and reliable method is beneficial for quantification and
      confirmation assays of multiply components in complex biological samples. 

PMID- 24295909
TI  - A HPLC-MS/MS method for the simultaneous quantitation of six alkaloids of Rhizoma
      Corydalis Decumbentis in rat plasma and its application to a pharmacokinetic
      study.
AB  - A specific and reliable HPLC-MS/MS method was developed and validated for the
      simultaneous determination of six alkaloids in rat plasma, jatrorrhizine,
      berberine, tetrahydropalmatine, protopine, bicuculline and palmatine. The
      analytes were separated on a C18 column (50mm*2.1mm, 1.8MUm) and a triple
      quadrupole mass spectrometry equipped with an electrospray ionization (ESI)
      source was used for detection. The plasma sample was prepared by the simple
      protein precipitation and the recovery for the six analytes was over 80%. The
      calibration curves were linear over a concentration range of 0.38-1900.0ng/mL for
      jatrorrhizine, 0.57-2850.0ng/mL for berberine, 0.32-1600.0ng/mL for
      tetrahydropalmatine, 0.21-1050.0ng/mL for protopine, 0.34-1700.0ng/mL for
      bicuculline and 0.22-1100ng/mL for palmatine. The intra-day and inter-day
      precision was less than 15% and the relative error (RE) was all within +/-15%.
      The validated method was successfully applied to a pharmacokinetics study in rats
      after oral administration of the extracts of Rhizoma Corydalis Decumbentis (a
      famous Chinese herb). 

PMID- 24295904
TI  - Miniaturized pre-clinical cancer models as research and diagnostic tools.
AB  - Cancer is one of the most common causes of death worldwide. Consequently,
      important resources are directed towards bettering treatments and outcomes.
      Cancer is difficult to treat due to its heterogeneity, plasticity and frequent
      drug resistance. New treatment strategies should strive for personalized
      approaches. These should target neoplastic and/or activated microenvironmental
      heterogeneity and plasticity without triggering resistance and spare host cells.
      In this review, the putative use of increasingly physiologically relevant
      microfabricated cell-culturing systems intended for drug development is
      discussed. There are two main reasons for the use of miniaturized systems. First,
      scaling down model size allows for high control of microenvironmental cues
      enabling more predictive outcomes. Second, miniaturization reduces reagent
      consumption, thus facilitating combinatorial approaches with little effort and
      enables the application of scarce materials, such as patient-derived samples.
      This review aims to give an overview of the state-of-the-art of such systems
      while predicting their application in cancer drug development. 

PMID- 24295910
TI  - Surface vibrational modes in disk-shaped resonators.
AB  - The natural frequencies and distributions of displacement components for the
      surface vibrational modes in thin isotropic elastic disks are calculated. In
      particular, the research is focused on even solutions for low-lying resonant
      vibrations with large angular wave numbers. Several families of modes are found
      which are interpreted as modified surface modes of an infinitely long cylinder
      and Lamb modes of a plate. The results of calculation are compared with the
      results of the experimental measurements of vibrational modes generated by means
      of resonant excitation in duraluminum disk with radius of ~90 mm and thickness of
      16 mm in the frequency range of 130-200 kHz. An excellent agreement between the
      calculated and measured frequencies is found. Measurements of the structure of
      the resonant peaks show splitting of some modes. About a half of the measured
      modes has splitting Deltafsplit/fmode at the level of the order of 10(-5). The Q
      factors of all modes measured in vacuum lie in the interval (2...3)*10(5). This
      value is typical for duraluminum mechanical resonators in the ultrasonic
      frequency range.

PMID- 24295911
TI  - Vibration characteristics of aluminum surface subjected to ultrasonic waves and
      their effect on wetting behavior of solder droplets.
AB  - The vibration characteristics of an aluminum surface subjected to ultrasonic
      waves were investigated with a combination of numerical simulation and
      experimental testing. The wetting behavior of solder droplets on the vibrating
      aluminum surface was also examined. The results show that the vibration pattern
      of the aluminum surface is inhomogeneous. The amplitude of the aluminum surface
      exceeds the excitation amplitude in some zones, while the amplitude decreases
      nearly to zero in other zones. The distribution of the zero-amplitude zones is
      much less dependent on the strength of the vibration than on the location of the
      vibration source. The surface of the liquid solder vibrates at an ultrasonic
      frequency that is higher than the vibration source, and the amplitude of the
      liquid solder is almost twice that of the aluminum surface. The vibration of the
      surface of the base metal (liquid solder) correlates with the oxide film removal
      effect. Significant removal of the oxide film can be achieved within 2s when the
      amplitude of the aluminum surface is higher than 5.4 MUm or when the amplitude of
      the liquid solder surface is higher than 10.2 MUm.

PMID- 24295912
TI  - Effect of aposymbiotic conditions on colony growth and secondary metabolite
      production in the lichen-forming fungus Ramalina dilacerata.
AB  - The production of secondary metabolites by aposymbiotic lichen-forming fungi in
      culture is thought to be influenced by environmental conditions. The effects of
      the environment may be studied by culturing fungi under defined growing
      parameters to provide a better understanding of the role of the large number of
      polyketide synthase (PKS) gene paralogs detected in the genomes of many fungi.
      The objectives of this study were to examine the effects of culture conditions
      (media composition and pH level) on the colony growth, the numbers of secondary
      products, and the expression of two PKS genes by the lichen-forming fungus
      Ramalina dilacerata. Four types of growth media at four different pH levels were
      prepared to culture spore isolates of R. dilacerata. Colony diameter and texture
      were recorded. The number of secondary compounds were determined by thin layer
      chromatography (TLC) and high performance liquid chromatography (HPLC).
      Expression of two PKS genes (non-reducing (NR) and 6-MSAS-type PKS) were compared
      with expression of an internal control mitochondrial small subunit gene (mtSSU).
      The results showed that media containing yeast extracts produced the largest
      colony diameters and the fewest number of secondary metabolites. Colony growth
      rates also varied with different media conditions, and a significant negative
      relationship occurred between colony diameter and number of secondary
      metabolites. Expression of the NR PKS gene was significantly higher at pH 6.5 on
      the glucose malt agar than any other media, and expression of the 6-MSAS-type
      (partially-reducing) PKS gene was significantly higher at pH 8.5 on (malt agar)
      malt agar than on the other types of agar. Gene expression was correlated with
      the pH level and media conditions that induced the production of the larger
      number of secondary substances. This is the first study to examine secondary
      metabolite production in R. dilacerata by comparing the number of polyketides
      detected with quantitative polymerase chain reaction (qPCR) of two PKS genes
      under different culture conditions. 

PMID- 24295913
TI  - Optimization of cellular uptake of zinc(II) 2,9,16,23-tetrakis[4-(N
      methylpyridyloxy)]phthalocyanine for maximal photoinactivation of Candida
      albicans.
AB  - Cellular uptake and photodynamic action of zinc(II) 2,9,16,23-tetrakis[4-(N
      methylpyridyloxy)]phthalocyanine (ZnPPc4+) was examined in Candida albicans. In
      vitro investigations showed that ZnPPc4+ was rapidly bound to C. albicans cells.
      The binding of phthalocyanine to cells was dependent on ZnPPc4+ concentrations (1
      10 MUM) and cells densities (106-108 cells mL-1). A high amount of ZnPPc4+
      retained in the cells after two washing steps, indicating a strong interaction
      between the photosensitizer and C. albicans. The uptake was temperature
      dependent, although the difference between 37  degrees C and 4  degrees C was
      about 10 %. Also, the amount of ZnPPc bound to C. albicans was affected when the
      cells were incubated for a longer time with azide and 2,4-dinitrophenol (DNP)
      prior to treatment with ZnPP4+. Cell survival after irradiation was dependent on
      the irradiation period, ZnPPc4+ concentration and cells density.
      Photoinactivation of C. albicans cells was elevated even after two washing steps.
      The strong dependence of uptake on cell density reveals the strength and avidity
      of the binding of ZnPPc4+ to C. albicans cells. The accumulation behaviour of
      ZnPPc4+ suggests that mainly an affinity-mediated binding mechanism can be
      involved. Therefore, ZnPPc4+ is an interesting phthalocyanine for photodynamic
      inactivation (PDI) of yeasts in liquid suspensions.

PMID- 24295914
TI  - Saprolegnia strains isolated from river insects and amphipods are broad spectrum
      pathogens.
AB  - Saprolegnia species are destructive pathogens to many aquatic organisms and are
      found in most parts of the world. Reports based on phylogenetic analysis suggest
      that Saprolegnia strains isolated from aquatic animals such as crustaceans and
      frogs are close to Saprolegnia strains isolated from infected fish or fish eggs
      and vice versa. However, it has often been assumed that host specificity occurs
      for each individual isolate or strain. Here we demonstrate that Saprolegnia spp.
      can have multiple hosts and are thus capable of infecting different aquatic
      organisms. Saprolegnia delica, Saprolegnia hypogyna, and 2 strains of Saprolegnia
      diclina were isolated from aquatic insects and amphipods while S. delica,
      Saprolegnia ferax, Pythium pachycaule, and a Pythium sp. were isolated from the
      water of a medium to fast flowing river. The ITS region of the rRNA gene was
      sequenced for all isolates. In challenge experiments, all four isolates from
      insects were found to be highly pathogenic to eggs of Atlantic salmon (Salmo
      salar) and embryos of the African clawed frog (Xenopus laevis). We found that
      Saprolegnia spp. isolated from salmon eggs were also able to successfully
      establish infection in nymphs of stonefly (Perla bipunctata) and embryos of X.
      laevis). These results suggest that Saprolegnia spp. are capable of infecting
      multiple hosts, which may give them an advantage during seasonal variation in
      their natural environments. 

PMID- 24295915
TI  - A three-gene phylogeny of the Mycena pura complex reveals 11 phylogenetic species
      and shows ITS to be unreliable for species identification.
AB  - Phylogenetic analyses of Mycena sect. Calodontes using ITS previously suggested
      ten cryptic monophyletic ITS lineages within the Mycena pura morphospecies. Here,
      we compare ITS data (645 bp incl. gaps) from 46 different fruit bodies that
      represent the previously described ITS diversity with partial tEF-1-alpha (423
      bp) and RNA polymerase II (RPB1) (492 bp) sequence data to test the genealogical
      concordance. While neither of the markers were in complete topological agreement,
      the branches differing between the tEF and RPB1 trees had a low bootstrap (<50)
      support, and the partition homogeneity incongruence length difference (ILD) tests
      were not significant. ILD tests revealed significant discordances between ITS and
      the tEF and RPB1 markers in several lineages. And our analyses suggested
      recombination between ITS1 and ITS2, most pronounced in one phylospecies that was
      identical in tEF and RPB1. Based on the agreement between tEF and RPB1, we
      defined 11 mutually concordant terminal clades as phylospecies inside the M. pura
      morphospecies; most of them cryptic. While neither of the markers showed an
      unequivocal barcoding gap between inter- and intraspecific diversity, the overlap
      was most pronounced for ITS (intraspecific diversity 0-3.5 %, interspecific
      diversity 0.4 %-8.8 %). A clustering analysis on tEF separated at a 1.5 % level
      returned all phylogenetic species as Operational Taxonomic Units (OTUs), while
      ITS at both a 1.5 % level and at a 3 % threshold level not only underestimated
      diversity as found by the tEF and RPB1, but also identified an OTU which was not
      a phylogenetic species. Thus, our investigation does not support the universal
      suitability of ITS for species recognition in particular, and emphasises the
      general limitation of single gene analyses combined with single percentage
      separation values. 

PMID- 24295916
TI  - Expression of Arabidopsis thaliana xylose isomerase gene and its effect on
      ethanol production in Flammulina velutipes.
AB  - To improve the pentose fermentation rate in Flammulina velutipes, the putative
      xylose isomerase (XI) gene from Arabidopsis thaliana was cloned and introduced
      into F. velutipes and the gene expression was evaluated in transformants. mRNA
      expression of the putative XI gene and XI activity were observed in two
      transformants, indicating that the putative gene from A. thaliana was
      successfully expressed in F. velutipes as a xylose isomerase. In addition,
      ethanol production from xylose was increased in the recombinant strains. This is
      the first report demonstrating the possibility of using plant genes as candidates
      for improving the characteristics of F. velutipes. 

PMID- 24295917
TI  - Cultivation of Tuber melanosporum in firebreaks: short-term persistence of the
      fungus and effect of seedling age and soil treatment.
AB  - Wildfires are a major threat to Mediterranean forests. Firebreaks are built as a
      prevention measure, but require a periodic and expensive maintenance. Cultivating
      the ectomycorrhizal mushroom Tuber melanosporum Vitt. in firebreaks could reduce
      costs and improve their sustainability. But firebreaks are built on forest soil,
      considered nonoptimum for T. melanosporum cultivation. A pot experiment was used
      to study the persistence of T. melanosporum in firebreak soils in the short term,
      as a first step to assess the viability of these plantations. The influence of
      seedlings, soil heating, and liming was also tested. During the 2 y after
      plantation, T. melanosporum mycorrhizas increased their number, showing its
      ability to proliferate. Percent root colonisation by native fungi importantly
      increased from month 12 to 22; although T. melanosporum remained dominant, with a
      colonisation level similar to those in standard truffle plantations. The age of
      seedlings at the time of planting influenced T. melanosporum proliferation,
      supporting a key role for nursery seedling quality in the performance of young
      plantations. Heating the soil before planting reduced the richness of native
      fungi, suggesting that this could increase plantation success. The results tend
      to support the viability of T. melanosporum cultivation in firebreaks, and
      encourage experimental field plantations.

PMID- 24295918
TI  - Evolutionary dynamics of introns and their open reading frames in the U7 region
      of the mitochondrial rnl gene in species of Ceratocystis.
AB  - The mtDNA rnl-U7 region has been examined for the presence of introns in selected
      species of the genus Ceratocystis. Comparative sequence analysis identified group
      I and group II introns encoding single and double motif LAGLIDADG open reading
      frames (ORFs) at the following positions L1671, L1787, and L1923. In addition
      downstream of the rnl-U7 region group I introns were detected at positions L1971
      and L2231, and a group II intron at L2059. A GIY-YIG type ORF was located within
      one mL1923 LAGLIDADG type ORF and a degenerated GIY-YIG ORF fused to a nad2 gene
      fragment was found in association with the mL1971 group I intron. The diversity
      of composite elements that appear to be sporadically distributed among closely
      related species of Ceratocystis illustrates the potential for homing
      endonucleases and their associated introns to invade new sites. Phylogenetic
      analysis showed that single motif LADGLIDADG ORFs related to the mL1923 ORFs have
      invaded the L1787 group II intron and the L1671 group I intron. Phylogenetic
      analysis of intron encoded single and double motif LAGLIDADG ORFs also showed
      that these ORFs transferred four times from group I into group II B1 type
      introns. 

PMID- 24295919
TI  - Molecular analysis reveals two new dimorphic species of Hesperomyces (Ascomycota,
      Laboulbeniomycetes) parasitic on the ladybird Coleomegilla maculata (Coleoptera,
      Coccinellidae).
AB  - Four morphotypes of Hesperomyces (Ascomycota, Laboulbeniomycetes) were found on
      the ladybird Coleomegilla maculata (Coleoptera, Coccinellidae) from Costa Rica
      and Ecuador. Partial SSU and ITS rDNA sequence analysis revealed that these
      belong to two phylogenetic species, each with a pair of morphotypes displaying
      position specificity. Confirmation of dimorphism in Laboulbeniales highlights the
      need for a thorough systematic revision of species concepts within the order. The
      theory of 'position specificity' also needs to be revisited. 

PMID- 24295920
TI  - The AreA transcription factor in Fusarium graminearum regulates the use of some
      nonpreferred nitrogen sources and secondary metabolite production.
AB  - Growth conditions are known to affect the production of secondary metabolites in
      filamentous fungi. The influence of different nitrogen sources and the
      transcription factor AreA on the production of mycotoxins in Fusarium graminearum
      was examined. Growth on glutamine or NH4-sources was poor and asparagine was
      found to be a preferential nitrogen source for F. graminearum. Deletion of areA
      led to poor growth on NaNO3 suggesting its involvement in regulation of the
      nitrate reduction process. In addition utilization of aspartic acid, histidine,
      isoleucine, leucine, threonine, tyrosine, and valine as nitrogen sources was
      shown to depend of a functional AreA. AreA was shown to be required for the
      production of the mycotoxins deoxynivalenol (DON), zearalenone, and fusarielin H
      regardless of the nutrient medium. Deletion of nmr, the repressor of AreA under
      nitrogen sufficient conditions, had little effect on either growth or toxin
      production. AreA appears to regulate production of some mycotoxins directly or
      indirectly independent on nitrogen status and plays a role in utilization of
      certain amino acids.

PMID- 24295921
TI  - Maternal inflammatory markers and term labor performance.
AB  - OBJECTIVE: We sought to examine the relationship between maternal markers of
      inflammation and labor performance. STUDY DESIGN: A nested cohort study was
      performed utilizing an established cohort of term nulliparous patients. Maternal
      blood was collected at the onset of regular, painful contractions in patients
      undergoing labor induction or at admission in patients with spontaneous labor.
      Levels of cytokines including interleukin (IL)-1, IL-6, and tumor necrosis factor
      alpha were determined using standard multiplex methodology. Maternal demographic
      data were collected prospectively. Detailed retrospective chart review was
      performed to extract data on cervical dilation, effacement, and station during
      labor. Subjects were excluded if they failed to achieve complete dilation. Mixed
      effects modeling was used to examine the association between serum cytokine
      quartiles and labor progress in the latent and active phases. RESULTS: In all,
      334 women were included in our analysis. The lowest quartile of IL-6 was
      associated with slower latent labor (P = .001). In contrast, the highest
      quartiles of IL-1 and tumor necrosis factor-alpha were associated with slower
      active labor (P = .03 and .0002, respectively). CONCLUSION: Proinflammatory
      activation is important in labor initiation. However, once active labor is
      established, excess inflammation can be detrimental to efficient labor progress.
      These data may explain, in part, the known associations among clinical
      chorioamnionitis, cesarean delivery, and postpartum hemorrhage.

PMID- 24295922
TI  - Racial and ethnic disparities in severe maternal morbidity: a multistate
      analysis, 2008-2010.
AB  - OBJECTIVE: The purpose of this study was to examine racial and ethnic disparities
      in severe maternal morbidity during delivery hospitalizations in the United
      States. STUDY DESIGN: We identified delivery hospitalizations from 2008-2010 in
      State Inpatient Databases from 7 states. We used International Classification of
      Diseases, 9th Revision, codes to create severe maternal morbidity indicators
      during delivery hospitalizations. We calculated the rates of severe maternal
      morbidity that were measured with and without blood transfusion for 5
      racial/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic,
      Asian/Pacific Islander, and American Indian/Alaska Native women. Poisson
      regression models were fitted to explore the associations between race/ethnicity
      and severe maternal morbidity after we controlled for potential confounders.
      RESULTS: Overall, severe maternal morbidity rates that were measured with and
      without blood transfusion were 150.7 and 64.3 per 10,000 delivery
      hospitalizations, respectively. Non-Hispanic black, Hispanic, Asian/Pacific
      Islander, and American Indian/Alaska Native women had 2.1, 1.3, 1.2, and 1.7
      times (all P < .05), respectively, higher rates of severe morbidity that were
      measured with blood transfusion compared with non-Hispanic white women; similar
      increased rates were observed when severe morbidity was measured without blood
      transfusion. Other significant positive predictors of severe morbidity were age
      <20 and >=30 years, self-pay or Medicaid coverage for delivery, low socioeconomic
      status, and presence of chronic medical conditions. CONCLUSION: Severe maternal
      morbidity disproportionally affects racial/ethnic minority women, especially non
      Hispanic black women. There is a need for a systematic review of severe maternal
      morbidities at the facility, state, and national levels to guide the development
      of quality improvement interventions to reduce the racial/ethnic disparities in
      severe maternal morbidity.

PMID- 24295923
TI  - Systematic review of robotic surgery in gynecology: robotic techniques compared
      with laparoscopy and laparotomy.
AB  - The Society of Gynecologic Surgeons Systematic Review Group performed a
      systematic review of both randomized and observational studies to compare robotic
      vs nonrobotic surgical approaches (laparoscopic, abdominal, and vaginal) for
      treatment of both benign and malignant gynecologic indications to compare
      surgical and patient-centered outcomes, costs, and adverse events associated with
      the various surgical approaches. MEDLINE and the Cochrane Central Register of
      Controlled Trials were searched from inception to May 15, 2012, for English
      language studies with terms related to robotic surgery and gynecology. Studies of
      any design that included at least 30 women who had undergone robotic-assisted
      laparoscopic gynecologic surgery were included for review. The literature yielded
      1213 citations, of which 97 full-text articles were reviewed. Forty-four studies
      (30 comparative and 14 noncomparative) met eligibility criteria. Study data were
      extracted into structured electronic forms and reconciled by a second,
      independent reviewer. Our analysis revealed that, compared with open surgery,
      robotic surgery consistently confers shorter hospital stay. The proficiency
      plateau seems to be lower for robotic surgery than for conventional laparoscopy.
      Of the various gynecologic applications, there seems to be evidence that renders
      robotic techniques advantageous over traditional open surgery for management of
      endometrial cancer. However, insofar as superiority, conflicting data are
      obtained when comparing robotics vs laparoscopic techniques. Therefore, the
      specific method of minimally invasive surgery, whether conventional laparoscopy
      or robotic surgery, should be tailored to patient selection, surgeon ability, and
      equipment availability. 

PMID- 24295924
TI  - Emotional false memories in children with learning disabilities.
AB  - Research has shown that children with learning disabilities (LD) are less prone
      to evince associative illusions of memory as a result of impairments in their
      ability to engage in semantic processing. However, it is unclear whether this
      observation is true for scripted life events, especially if they include
      emotional content, or across a broad spectrum of learning disabilities. The
      present study addressed these issues by assessing recognition memory for script
      like information in children with nonverbal learning disability (NLD), children
      with dyslexia, and typically developing children (N=51). Participants viewed
      photographs about 8 common events (e.g., family dinner), and embedded in each
      episode was either a negative or a neutral consequence of an unseen action.
      Children's memory was then tested on a yes/no recognition task that included old
      and new photographs. Results showed that the three groups performed similarly in
      recognizing target photographs, but exhibited differences in memory errors.
      Compared to other groups, children with NLD were more likely to falsely recognize
      photographs that depicted an unseen cause of an emotional seen event and
      associated more "Remember" responses to these errors. Children with dyslexia were
      equally likely to falsely recognize both unseen causes of seen photographs and
      photographs generally consistent with the script, whereas the other participant
      groups were more likely to falsely recognize unseen causes rather than script
      consistent distractors. Results are interpreted in terms of mechanisms underlying
      false memories' formation in different clinical populations of children with LD. 

PMID- 24295926
TI  - Anticipation of a psychosocial stressor differentially influences ghrelin,
      cortisol and food intake among emotional and non-emotional eaters.
AB  - Negative emotions trigger eating in some individuals (emotional eaters) possibly
      by influencing stress hormones that contribute to eating regulation (e.g.,
      cortisol), or eating-related peptides (e.g., ghrelin) signaling food initiation.
      The present study assessed whether stressor-elicited cortisol and ghrelin changes
      would differ between emotional and non-emotional eaters, and whether eating would
      influence these neuroendocrine responses. Undergraduate women (N=103) who
      completed measures of emotional eating, were assigned to anticipate either a
      stressful (public speaking) or non-stressful event. During this period,
      participants were or were not offered food. Blood samples were taken continuously
      over a 40-min period to assess changes of cortisol and ghrelin levels, and mood
      was assessed after the anticipation period. Baseline ghrelin levels were lower in
      emotional than non-emotional eaters, and this relation was mediated by percent
      body fat. Ghrelin levels were elevated among women anticipating a stressor,
      compared to those in the control condition. Additionally, the normal decline of
      ghrelin following food consumption was not apparent among emotional eaters.
      Although food intake was not tied to hormone responses, reported hunger was
      associated with greater food intake for women in the stressor condition. It was
      suggested that emotional eating coupled with subjective feelings of hunger, might
      contribute to eating in response to an acute stressor. Additionally, feedback
      mechanisms controlling the normalization of ghrelin levels might be disturbed in
      emotional eaters. The similarity of the ghrelin profile of emotional eaters to
      that of binge eaters and obese individuals, raises the possibility that disturbed
      ghrelin response might be a risk factor for such conditions. 

PMID- 24295927
TI  - Food and wellbeing. Towards a consumer-based approach.
AB  - Interest in understanding how foods affect consumers' perceived wellbeing has
      grown in the last decade due to the increasing need to modify dietary patterns.
      Considering that wellbeing is a broad concept that lacks of a unique definition,
      in order to use and measure this concept it is necessary to explore how consumers
      understand it, particularly in the context of food consumption. The aim of the
      present work was to investigate consumers' perception of wellbeing in a food
      related context using an exploratory qualitative approach. A study was carried
      out with 120 Uruguayan participants using three qualitative techniques: word
      association, open-ended questions and free listing. Wellbeing in a food-related
      context was strongly associated with physical health. The expected effects of
      foods on wellbeing were mainly related to non-communicable diseases such as high
      cholesterol levels, hypertension, and cardiovascular diseases. However, hedonic
      and emotional aspects of food consumption were also salient for consumers
      perceived wellbeing. The information gathered in this study can contribute to the
      development of scales for measuring consumer perceived wellbeing when consuming
      foods. 

PMID- 24295928
TI  - The Christchurch earthquake stroke incidence study.
AB  - We examined the impact of major earthquakes on acute stroke admissions by a
      retrospective review of stroke admissions in the 6 weeks following the 4
      September 2010 and 22 February 2011 earthquakes. The control period was the
      corresponding 6 weeks in the previous year. In the 6 weeks following the
      September 2010 earthquake there were 97 acute stroke admissions, with 79 (81.4%)
      ischaemic infarctions. This was similar to the 2009 control period which had 104
      acute stroke admissions, of whom 80 (76.9%) had ischaemic infarction. In the 6
      weeks following the February 2011 earthquake, there were 71 stroke admissions,
      and 61 (79.2%) were ischaemic infarction. This was less than the 96 strokes (72
      [75%] ischaemic infarction) in the corresponding control period. None of the
      comparisons were statistically significant. There was also no difference in the
      rate of cardioembolic infarction from atrial fibrillation between the study
      periods. Patients admitted during the February 2011 earthquake period were less
      likely to be discharged directly home when compared to the control period (31.2%
      versus 46.9%, p=0.036). There was no observable trend in the number of weekly
      stroke admissions between the 2 weeks leading to and 6 weeks following the
      earthquakes. Our results suggest that severe psychological stress from
      earthquakes did not influence the subsequent short term risk of acute stroke, but
      the severity of the earthquake in February 2011 and associated civil structural
      damages may have influenced the pattern of discharge for stroke patients.

PMID- 24295930
TI  - Could a Visual Analogue Scale be useful, in real life, to manage children with
      asthma?

PMID- 24295929
TI  - Dietary patterns in Asian Indians in the United States: an analysis of the
      metabolic syndrome and atherosclerosis in South Asians Living in America study.
AB  - Dietary patterns contribute to cardiovascular disease (CVD) risk. Asian Indians
      have earlier onset, more severe, and more prevalent CVD than many other
      racial/ethnic groups. We aimed to characterize dietary patterns in Asian Indians
      living in the United States and examine associations with cardiometabolic risk
      factors. One hundred fifty Asian Indians, aged 45 to 84 years, without known CVD,
      living in the San Francisco Bay, CA, area between August 2006 and October 2007
      were enrolled into the Metabolic syndrome and Atherosclerosis in South Asians
      Living in America study. A food frequency questionnaire validated in Asian
      Indians, fasting blood samples, and computed tomography scans were obtained for
      all participants. Principal component analysis with varimax rotation was used to
      determine prevalent dietary patterns. Linear regression analyses were performed
      for associations between dietary patterns and metabolic factors, adjusting
      initially for age and sex, then additionally for BMI, income, education,
      metabolic equivalent of task-minutes of exercise, alcohol consumption, and
      smoking. Two distinct dietary patterns were identified that we termed "Western,"
      and "Vegetarian." Compared with the Western diet, the Vegetarian diet was
      associated with lower homeostasis model of assessment-insulin resistance (-1.12
      mmol/L * mU/L; P=0.05) and lower high-density lipoprotein cholesterol (-4.77
      mg/dL; P=0.09). Given that the Western and Vegetarian dietary patterns were each
      associated with adverse metabolic changes, healthful diet choices may help Asian
      Indians improve risk factors for CVD.

PMID- 24295932
TI  - ICD 9-10-11 whoa!

PMID- 24295933
TI  - Imaging screening: harder than it looks.

PMID- 24295931
TI  - Comparative assessment of a biofilter, a biotrickling filter and a hollow fiber
      membrane bioreactor for odor treatment in wastewater treatment plants.
AB  - A low abatement efficiency for the hydrophobic fraction of odorous emissions and
      a high footprint are often pointed out as the major drawbacks of conventional
      biotechnologies for odor treatment. In this work, two conventional
      biotechnologies (a compost-based biofilter, BF, and a biotrickling filter, BTF),
      and a hollow-fiber membrane bioreactor (HF-MBR) were comparatively evaluated in
      terms of odor abatement potential and pressure drop (DeltaP) at empty bed
      residence times (EBRTs) ranging from 4 to 84 s, during the treatment of methyl
      mercaptan, toluene, alpha-pinene and hexane at trace level concentrations (0.75
      4.9 mg m(-3)). High removal efficiencies (RE > 90% regardless of the air
      pollutant) were recorded in the BF at EBRTs >= 8 s, although the high DeltaP
      across the packed bed limited its cost-effective operation to EBRTs > 19 s. A
      complete methyl-mercaptan, toluene and alpha-pinene removal was recorded in the
      BTF at EBRTs >= 4 s and DeltaP lower than 33 mmH2O (~611 Pa mbed(-1)), whereas
      slightly lower REs were observed for hexane (~88%). The HF-MBR completely removed
      methyl-mercaptan and toluene at all EBRTs tested, but exhibited an unstable alpha
      pinene removal performance as a result of biomass accumulation and a low hexane
      abatement efficiency. Thus, a periodical membrane-cleaning procedure was required
      to ensure a steady abatement performance. Finally, a high bacterial diversity was
      observed in the three bioreactors in spite of the low carbon source spectrum
      present in the air emission. 

PMID- 24295934
TI  - Reference pricing.

PMID- 24295935
TI  - Radiologists and disability access requirements.

PMID- 24295936
TI  - Introduction to the Special Issue--Imaging-based screening: radiology's
      increasing role in preventive medicine.

PMID- 24295937
TI  - Dense breast legislation in the United States: state of the states.
AB  - Limitations of screening mammography in patients with dense breasts combined with
      the significant increased risk for breast cancer have made the issue of dense
      breasts a matter of great concern in recent years, leading to advocacy for policy
      change and legislation. Dense breast notification legislation requires direct
      patient notification of mammographic results indicating the presence of dense
      breast tissue. The aim of this study was to summarize the state of dense breast
      notification legislation across the country. The general intent of dense breast
      notification legislation is to increase awareness of dense breasts and encourage
      patients to discuss the clinical issues with their physicians. It was first
      enacted in Connecticut in 2009, and since then, 27 other states have passed,
      rejected, or considered dense breast notification legislation. At the federal
      level, a bill was introduced in October 2011, but it was not enacted. There are
      significant differences in the language of the laws from state to state that
      complicate implementation. Furthermore, legislated recommendations for possible
      additional testing are often unaccompanied by legal provisions for insurance
      coverage, which potentially results in unequal access.

PMID- 24295938
TI  - Decade of 'normal' mammography reports--the happygram.
AB  - Interest in breast density reporting legislation has accelerated in the past
      several years, driven primarily by patients turned advocates under the mentorship
      and leadership of Are You Dense, Inc, and Are You Dense Advocacy, Inc. The
      history of the density reporting movement and the birth of education and advocacy
      nonprofits are described, along with how legislative efforts began. The decades
      of scientific research on dense tissue's masking effect and its being established
      as an independent risk factor for breast cancer are summarized. Finally, the
      opposition's arguments against density reporting legislation are addressed. 

PMID- 24295939
TI  - The density conundrum: does legislation help or hurt?
AB  - Breast density and breast density legislation are controversial and potentially
      emotional issues in breast screening. Informing individual patients of their
      breast density status is an extremely important and highly personal conversation
      that must focus on patients' specific situations. The unanswered questions about
      converting population risk make it difficult to provide an individual woman with
      an explanation of what breast density means to her individual risk for developing
      breast cancer now or in the future. There are no standards or guidelines for what
      doctors should tell patients about their risk with dense breasts, and legislating
      the conversation may not improve it or a woman's response to the information. It
      is necessary to learn more about breast density, understand its meaning, and
      communicate clearly and compassionately with patients about what we know and what
      we do not know about breast cancer risk. Precipitous legislation can, in fact,
      undermine both the patient-physician relationship and the need for more evidence
      that would expand our understanding of the risk associated with breast density. 

PMID- 24295940
TI  - Digital breast tomosynthesis and the challenges of implementing an emerging
      breast cancer screening technology into clinical practice.
AB  - Emerging imaging technologies, including digital breast tomosynthesis, have the
      potential to transform breast cancer screening. However, the rapid adoption of
      these new technologies outpaces the evidence of their clinical and cost
      effectiveness. The authors describe the forces driving the rapid diffusion of
      tomosynthesis into clinical practice, comparing it with the rapid diffusion of
      digital mammography shortly after its introduction. They outline the potential
      positive and negative effects that adoption can have on imaging workflow and
      describe the practice management challenges when incorporating tomosynthesis. The
      authors also provide recommendations for collecting evidence supporting the
      development of policies and best practices. 

PMID- 24295941
TI  - Evolving paradigm for imaging, diagnosis, and management of DCIS.
AB  - Our understanding of the biology of breast cancer has dramatically expanded over
      the past decade, revealing that breast cancer is a heterogeneous group of
      diseases. This new knowledge can generate insights to improve screening
      performance and the management of ductal carcinoma in situ. In this article, the
      authors review the current state of the science of breast cancer and tools that
      can be used to improve screening and risk assessment. They describe several
      opportunities to improve clinical screening: (1) radiologists interpreting
      mammograms should aim to differentiate between the risk for invasive cancer and
      ductal carcinoma in situ to better assess the time frame for disease progression
      and the need for and optimal timing of biopsy; (2) imaging features associated
      with low risk, slow-growing cancer versus high risk, fast-growing cancer should
      be better defined and taught; and (3) as we learn more about assessing an
      individual's risk for developing breast cancer, we should incorporate these
      factors into a strategy for personalized screening to maximize benefit and
      minimize harm. 

PMID- 24295942
TI  - Performance goals for an adjunct diagnostic test to reduce unnecessary biopsies
      after screening mammography: analysis of costs, benefits, and consequences.
AB  - PURPOSE: Because benign biopsies resulting from false-positive mammographic
      findings are a known harm of breast cancer screening, physicians and test
      manufacturers are searching for ways to reduce their frequency. The aim of this
      study was to estimate potential costs and consequences associated with using an
      adjunct diagnostic test for triaging women with suspicious mammographic findings
      before biopsy. METHODS: A decision model was developed to compare the use of an
      adjunct test before biopsy to the current standard of care for suspicious
      mammographic findings. The decision analysis was performed from the perspective
      of a national health payer, with a 1-year time horizon among women representative
      of the US screening population aged 40 to 79 years. Three primary outcomes were
      assessed: (1) incremental costs, (2) number of benign biopsies avoided, and (3)
      number of missed opportunities for diagnosing cancer per million women screened.
      Input parameters were obtained from the medical literature and expert opinion.
      Sensitivity analyses were performed to evaluate the effects of uncertainty in
      parameter estimates. RESULTS: The base-case analysis demonstrated that the use of
      an adjunct diagnostic test with 95% sensitivity, 75% specificity, and a cost of
      $1,000 would eliminate 8,127 unnecessary breast biopsies per million women
      screened. However, this would cost the US health care system an additional
      $6,462,977 and result in 255 missed opportunities for diagnosing cancer per
      million women screened. CONCLUSIONS: The addition of an adjunct test for triaging
      women for breast biopsy after abnormal findings on screening mammography would
      likely eliminate many unnecessary biopsies but also increase overall health care
      costs. This exploratory analysis highlights the fact that mammography remains a
      relatively inexpensive and effective breast cancer screening and diagnostic
      modality.

PMID- 24295943
TI  - Controversies in lung cancer screening.
AB  - There remains an extensive debate over lung cancer screening, with lobbying for
      and against screening for very compelling reasons. The National Lung Screening
      Trial, International Early Lung Cancer Program, and other major screening studies
      favor screening with low-dose CT scans and have shown a reduction in lung cancer-
      specific mortality. The increasing incidence of lung cancer and the dismal
      survival rate for advanced disease despite improved multimodality therapy have
      sparked an interest in the implementation of national lung cancer screening.
      Concerns over imaging workflow, radiation dose, management of small nodules,
      overdiagnosis bias, lead-time and length-time bias, emerging new technologies,
      and cost-effectiveness continue to be debated. The authors address each of these
      issues as they relate to radiologic practice.

PMID- 24295944
TI  - The challenges of CT colonography reimbursement.
AB  - CT colonography has been shown to be an effective method to screen for colorectal
      cancer. However, at present, full endorsement and reimbursement for screening CT
      colonography, particularly by the US Preventive Services Task Force and CMS,
      respectively, are absent, so this screening option is infrequently used, and
      optical colonoscopy remains the de facto standard screening option. The authors
      summarize the past accomplishments that led to the current state of reimbursement
      and outline the remaining challenges and road to full acceptance and
      reimbursement of screening CT colonography nationally. 

PMID- 24295945
TI  - Emerging and evolving roles for CT in screening for coronary heart disease.
AB  - Coronary heart disease (CHD) is highly prevalent and is the primary cause of
      death for both men and women, worldwide. Because the disease develops over many
      years, there are opportunities to intervene and alter the course of CHD, assuming
      that there are reliable means for determining which individuals with coronary
      atherosclerosis will develop symptomatic CHD. CT provides 2 distinct means for
      coronary artery disease assessment--coronary artery calcium (CAC) measurement
      using noncontrast CT and coronary CT angiography (cCTA). The recent refinement of
      electrocardiographic triggering and gating with CT has enabled these techniques
      to be performed with greater reliability and substantially lower radiation
      exposure. This has led to widening availability of these diagnostic techniques
      and rapid expansion of our understanding of their potential clinical use. Within
      the context of CHD, 2 applications are particularly compelling--risk
      stratification of asymptomatic individuals with the intent of targeting therapy
      to prevent CHD and as gatekeeper to cardiac catheterization to minimize
      unnecessary invasive diagnostic coronary procedures. This review highlights key
      insights from recent investigations of CHD development and CT application toward
      the management of individuals at risk of developing or suspected of having CHD.

PMID- 24295946
TI  - Screening and insurance.
AB  - The author discusses the economics and regulation of the health insurance
      industry as they pertain to imaging-based screening programs in light of the
      Patient Protection and Affordable Care Act. 

PMID- 24295947
TI  - Managing incidental findings on abdominal and pelvic CT and MRI, Part 4: white
      paper of the ACR Incidental Findings Committee II on gallbladder and biliary
      findings.
AB  - This white paper describes gallbladder and biliary incidental findings found on
      CT and MRI. Recommendations for management are included. This represents the
      fourth of 4 such papers from the ACR Incidental Findings Committee II, which used
      a consensus method based on repeated reviews and revisions and a collective
      review and interpretation of relevant literature. Topics include the management
      of a variety of gallbladder abnormalities and biliary dilation. A table is
      provided for reference. 

PMID- 24295948
TI  - Examining barriers for mammography screening compliance within a private hospital
      and an underserved primary care clinic in Santiago, Chile.

PMID- 24295949
TI  - Leadership--the last 100 days.

PMID- 24295950
TI  - Abolishing fee-for-service reimbursement is good for the profession of radiology:
      a debate from the 2013 AMCLC, Resident and Fellow Section meeting.

PMID- 24295951
TI  - The ACR Computed Tomography Dose Index Registry: the 5 million examination
      update.

PMID- 24295952
TI  - A practical fluorometric assay method to measure lysosomal acid lipase activity
      in dried blood spots for the screening of cholesteryl ester storage disease and
      Wolman disease.
AB  - Fluorometric measurements of 4-methylumbelliferone (4-MU) are generally used to
      screen lysosomal storage diseases (LSDs) using dried blood spots (DBSs). However,
      in DBS, it is difficult to measure lysosomal acid lipase (LAL) activity due to
      the influence of other lipases in whole blood. Recently, Hamilton used a
      fluorometric enzyme assay with 4-MU derivatives to measure the LAL activity in
      DBS. This method requires mercury chloride as stopping reagent, and the
      fluorescence intensity of 4-MU was measured at an acidic pH. We report a revised
      method to measure the LAL activity without using toxic mercury chloride and to
      measure the fluorescence intensity of 4-MU at a basic pH. For this measurement,
      we established a more practical method that does not require mercury chloride.
      The LAL activity in DBS was measured in 51 normal controls, seven obligate
      carriers and seven patients with CESD. The average LAL activities +/- SD in the
      DBS from the normal, obligate carriers and CESD patients were 0.68 +/- 0.2
      (range: 0.3-1.08), 0.21 +/- 0.1 (range: 0.11-0.41) and 0.02 +/- 0.02 (range: 0
      0.06) nmol/punch/h, respectively. There was a significant difference between the
      normal and the CESD. Our method does not require toxic mercury chloride and is an
      appropriate revised enzyme assay using DBS for screening patients with CESD.

PMID- 24295953
TI  - Epidemiology of Leishmania infantum, Toxoplasma gondii, and Neospora caninum in
      Rattus rattus in absence of domestic reservoir and definitive hosts.
AB  - Isolated environments are privileged settings to study transmission of infection.
      Montecristo is a small island where no wild or domestic carnivores are present.
      Invasive Black rats Rattus rattus (n=78) were captured and tested by PCR for
      Leishmania infantum, Toxoplasma gondii and Neospora caninum. We wanted to test,
      for these parasites, the existence of a sylvatic cycle independent of reservoir
      or definitive hosts. None of the rats tested positive by PCR for either T. gondii
      or N. caninum. We recorded a 15.5% prevalence (CI95% 8-26%) of L. infantum in the
      rats and Phlebotomus mascittii was captured in Montecristo, leading us to
      identify it as possible vector of the parasite.

PMID- 24295954
TI  - Neospora caninum is a cause of perinatal mortality in axis deer (Axis axis).
AB  - Neospora caninum is a worldwide distributed protozoan that may cause
      neuromuscular disease in dogs and reproductive failure in domestic and wild
      ruminants. One axis fawn (Axis axis) and four neonates from the same deer herd
      died at a zoo in Argentina within a four-month period. The fawn presented with
      dilatation of the anal sphincter at birth and incontinence, developed weakness
      and ataxia and died at 14 days of age. At necropsy, a mega formation of the
      distal large intestine was observed. Microscopically, non-suppurative
      encephalitis, suppurative bronchopneumonia, fibrin necrotic enteritis and
      degenerative changes in the liver were observed in hematoxilin and eosin-stained
      tissue sections, and thick-walled N. caninum-like cysts were observed in fresh
      brain samples. Serologic studies for N. caninum revealed an IFAT titer of 1:6400
      in the fawn and 1:25, 1:400, 1:3200 and 1:6400 in the neonates. N. caninum DNA
      was detected in brain samples from the fawn and from one neonate by PCR, and the
      parasite was isolated in vitro from the fawn' brain after passage through gerbils
      (Meriones unguiculatus) and gamma-interferon knock-out mice. N. caninum DNA
      obtained from the fawn, neonate and isolated parasites showed the same
      microsatellite pattern. This suggests a common infection source for both animals.
      The diagnosis of N. caninum infection was confirmed, suggesting its association
      with perinatal mortality in captive axis deer. To the best of our knowledge, this
      is the first report of clinical disease associated to N. caninum infection in
      axis deer and of isolation of the parasite from this wild ruminant species.

PMID- 24295955
TI  - Identification and quantification of benzimidazole resistance polymorphisms in
      Haemonchus contortus isolated in Northeastern Brazil.
AB  - Haemonchus contortus is the most prevalent nematode in Brazil. The objective of
      this study was to select 6 populations of H. contortus of known or suspected
      benzimidazole resistance status and characterize these using quantitative real
      time polymerase chain reaction (qPCR) for single nucleotide polymorphisms (SNPs)
      F200Y, F167Y and E198A in the beta-tubulin isotype 1 gene. qPCR was performed
      using DNA from a pool of 10 adult male H. contortus from a single animal per
      farm. Faecal egg count reduction test (FECRT) and egg hatch test (EHT) were used
      to determine the resistance status. Samples were obtained from 6 farms located in
      5 counties in the Ceara State: Taua, Boa Viagem, Quixada, Santa Quiteria and
      Solonopole. The inbred-susceptible-Edinburgh (ISE) isolate was used as reference
      for comparative purposes in the qPCR. Benzimidazole resistance was detected by
      FECRT on all farms with efficacy values ranging from 0 to 51%. EC50 values as
      determined by EHT were all above 1.49MUg/ml. High frequencies of the resistant
      SNPs F200Y and F167Y alleles were detected but no resistance was detected at SNP
      E198A. Our results suggest that the SNPs F167Y and F200Y are both important for
      benzimidazole resistance in the studied populations.

PMID- 24295956
TI  - Calicophoron daubneyi (Paramphistomidae) in slaughtered cattle in Castilla y Leon
      (Spain).
AB  - The prevalence and aetiology of natural paramphistomosis was investigated in
      cattle slaughtered in the Castilla y Leon region (Spain) over a 3 year-period.
      The overall prevalence of positive animals was 6.20%. The parasite burden per
      animal ranged from 8 to 8005 (median=144) and the ruminal atrium had the highest
      parasite burden whereas the ruminal dorsal sac the lowest. The prevalence and
      parasite burden increased with age while these parameters were lower in cattle
      under intensive management. Calicophoron daubneyi was the only Paramphistomidae
      species identified using morphoanatomical, histological and molecular methods in
      the studied animals. 

PMID- 24295957
TI  - Isolation of active compounds from methanol extracts of Toddalia asiatica against
      Ichthyophthirius multifiliis in goldfish (Carassius auratus).
AB  - The parasitic ciliate Ichthyophthirius multifiliis infests all species of
      freshwater fish and can cause severe economic losses in fish breeding. The
      present study aims to evaluate the antiparasitic activity of the active
      components from Toddalia asiatica against I. multifiliis. Bioassay-guided
      fractionation and isolation of compounds with antiparasitic activity were
      performed on the methanol extract of T. asiatica yielding two bioactive
      compounds: chelerythrine and chloroxylonine identified by comparing spectral data
      (NMR and ESI-MS) with literature values. Results from in vitro antiparasitic
      assays revealed that chelerythrine and chloroxylonine could be 100% effective
      against I. multifiliis at the concentration of 1.2 mg L(-1) and 3.5 mg L(-1),
      with the median effective concentration (EC50) values of 0.55 mg L(-1) and 1.90
      mg L(-1) respectively. In vivo experiments demonstrated that fish treated with
      chelerythrine and chloroxylonine at the concentrations of 1.8 and 8.0 mg L(-1)
      carried significantly fewer parasites than the control (P<0.05). The acute
      toxicity (LC50) of chelerythrine for goldfish was 3.3 mg L(-1).

PMID- 24295958
TI  - In vitro evaluation of the ovistatic and ovicidal effect of the cosmopolitan
      filamentous fungi isolated from soil on Ascaris suum eggs.
AB  - The ovicidal activity of seven fungal strains: Acremonium alabamense, Alternaria
      chlamydospora, Cladosporium herbarum, Fusarium solani, Paecilomyces variotii,
      Paecilomyces viridis and Penicillium verruculosum isolated from urban soil
      samples from Poland was determined in vitro. The fungal mycelium was co-cultured
      with Ascaris suum eggs on plates with 2% water-agar for 28 days. Eggs exposed and
      unexposed (control) to fungal mycelium were observed weekly by light microscopy
      and the percentage of malformed eggs were determined. The eggs were classified
      according to following parameters: type 1 - biochemical and physiological effect
      without morphological damage to the eggshell; type 2 - lytic effect with
      morphological alteration of the eggshell and embryo; type 3 - lytic effect with
      morphological alteration of eggshell and embryo with hyphal penetration and
      internal egg colonization. All examined species of fungi extended embryogenesis,
      but the retardation of embryonic development was varied and depended on the
      species. A. alabamense, A. chlamydospora and P. verruculosum exhibited very high
      inhibitory activity on A. suum egg development. The fungus-exposed eggs revealed
      morphological alternations in all stages of embryogenesis. Isolates of F. solani,
      P. variotii and P. viridis showed hyphal penetration and internal colonization of
      A. suum eggs (type 3 effect). No appressoria were produced and simple hyphal
      penetrations were most commonly observed. A. alabamense and P. verruculosum
      demonstrated morphological destruction, with eggshell destruction. The remaining
      fungi showed type 1 effect. The results demonstrated that examined strains of F.
      solani, P. variotii and P. viridis may be considered to be potential limiting
      factors of parasitic geohelminth populations.

PMID- 24295959
TI  - Hyperglycaemia modifies energy metabolism and reactive oxygen species formation
      in endothelial cells in vitro.
AB  - There is significant evidence for an involvement of reactive oxygen species (ROS)
      in the pathogenesis of diabetic vascular complications through many metabolic and
      structural derangements. However, despite the advanced knowledge on the crucial
      role of ROS in cardiovascular damage, their intracellular source in endothelial
      cells exposed to high concentrations of glucose has not been precisely defined.
      Moreover, the molecular mechanism of action of elevated glucose on mitochondria
      has not been fully elucidated. The main aim of this study was to describe changes
      in the mitochondrial metabolism of human umbilical vein endothelial cells
      (HUVECs) treated with high glucose concentrations and to indicate the actual
      source of ROS in these cells. HUVECs exposed to 30 mM glucose exhibited an
      increased content of vascular adhesive molecule-1 (VCAM-1) and an excessive ROS
      production. Faster oxygen consumption and increased abundance of selected
      respiratory complexes coexist with slightly declined mitochondrial membrane
      potential and substantially elevated amount of uncoupling protein-2 (UCP2).
      Inhibition of NADPH oxidase (NOX) and modification of mitochondrial ROS
      generation with a mitochondrial uncoupler or respiratory chain inhibitors allowed
      concluding that the major source of ROS in HUVECs exposed to hyperglycaemic
      conditions is NOX. The mitochondrial respiratory chain seems not to participate
      in this phenomenon.

PMID- 24295960
TI  - Heme-dependent dioxygenases in tryptophan oxidation.
AB  - L-Tryptophan is an essential amino acid for mammals. It is utilized not only for
      protein synthesis but also for the biosynthesis of serotonin and melatonin by the
      serotonin pathway as well as nicotinamide adenine dinucleotide by the kynurenine
      pathway. Although the kynurenine pathway is responsible for the catabolism of
      over 90% of l-tryptophan in the mammalian intracellular and extracellular pools,
      the scientific field was dominated in the last century by studies of the
      serotonin pathway, due to the physiological significance of the latter's
      catabolic intermediates and products. However, in the past decade, the focus
      gradually reversed as the link between the kynurenine pathway and various
      neurodegenerative disorders and immune diseases is increasingly highlighted.
      Notably, the first step of this pathway, which is catalyzed by heme-dependent
      dioxygenases, has been proven to be a potential target for immune regulation and
      cancer treatment. A thorough understanding of the intriguing chemistry of the
      heme-dependent dioxygenases may yield insight for the drug discovery of these
      prevalent illnesses. In this review, we survey enzymatic and mechanistic studies,
      initially started by Kotake and Masayama over 70 years ago, at the molecular
      level on the heme-dependent tryptophan dioxygenation reactions.

PMID- 24295961
TI  - Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.
AB  - Atopic dermatitis (AD) is a common skin disease that greatly worsens quality of
      life. Thymic stromal lymphopoietin (TSLP) plays a decisive role in the
      development of AD. The purpose of this study is to examine whether tryptanthrin
      (TR) would suppress AD through the regulation of TSLP. We analyzed the effect of
      TR on the level of TSLP from phorbol myristate acetate/calcium ionophore A23187
      activated human mast cell line, HMC-1 cells, in 2,4-dinitrofluorobenzene-induced
      AD-like skin lesions of NC/Nga mice, and in anti-CD3/anti-CD28-stimulated
      splenocytes. TR significantly suppressed the level of intracellular calcium and
      the production and mRNA expression of TSLP through the blockade of receptor
      interacting protein 2/caspase-1/nuclear factor-kappaB pathway in the activated
      HMC-1 cells. TR also significantly suppressed the levels of histidine
      decarboxylase and IL-1beta. Furthermore, TR ameliorated clinical symptoms in the
      AD model. TR significantly reduced the levels of TSLP, IL-4, IFN-gamma, IL-6, TNF
      alpha, thymus and activation-regulated chemokine, and caspase-1 in AD skin
      lesions. Also, TR significantly reduced the serum levels of histamine and IL-4 in
      the AD model. Finally, TR significantly inhibited the production of IL-4, IFN
      gamma, and TNF-alpha from the stimulated splenocytes. Taken together, TR exhibits
      the potential to be a therapeutic agent for AD through down-regulation of TSLP. 

PMID- 24295962
TI  - Enzyme allocation problems in kinetic metabolic networks: optimal solutions are
      elementary flux modes.
AB  - The survival and proliferation of cells and organisms require a highly
      coordinated allocation of cellular resources to ensure the efficient synthesis of
      cellular components. In particular, the total enzymatic capacity for cellular
      metabolism is limited by finite resources that are shared between all enzymes,
      such as cytosolic space, energy expenditure for amino-acid synthesis, or micro
      nutrients. While extensive work has been done to study constrained optimization
      problems based only on stoichiometric information, mathematical results that
      characterize the optimal flux in kinetic metabolic networks are still scarce.
      Here, we study constrained enzyme allocation problems with general kinetics,
      using the theory of oriented matroids. We give a rigorous proof for the fact that
      optimal solutions of the non-linear optimization problem are elementary flux
      modes. This finding has significant consequences for our understanding of
      optimality in metabolic networks as well as for the identification of metabolic
      switches and the computation of optimal flux distributions in kinetic metabolic
      networks. 

PMID- 24295963
TI  - An age-corrected matched-pair study of erectile function in patients treated with
      dose-escalated adaptive image-guided intensity-modulated radiation therapy vs.
      high-dose-rate brachytherapy for prostate cancer.
AB  - PURPOSE: To compare erectile dysfunction (ED) after adaptive dose-escalated image
      guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial
      brachytherapy (HDR) monotherapy. METHODS AND MATERIALS: Low- and intermediate
      risk prostate cancer patients treated with IG-IMRT or HDR were matched on
      pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen.
      Patients who received androgen deprivation therapy were excluded. ED was graded
      by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were
      computed by the Kaplan-Meier method. RESULTS: There were 384 patients with median
      followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The
      median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For
      patients with no pretreatment ED, actuarial rates of requiring intervention
      (Grade >=2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and
      impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for
      HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade >=2 ED at 3 years
      were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both
      groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years
      were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of
      Grade >=2 ED following treatment. CONCLUSIONS: Rates of ED requiring medical
      intervention for both IG-IMRT and HDR are low and equivalent. Even patients with
      ED before treatment are likely to maintain potency with medication use at 3 years
      following treatment.

PMID- 24295964
TI  - A proposal for the stratification of the risk of locoregional failure after
      surgical resection, perioperative high dose rate brachytherapy, and external beam
      irradiation: the University of Navarre predictive model.
AB  - PURPOSE: To develop a simple clinical model predictive of locoregional failure
      after complete surgical resection followed by perioperative high-dose-rate
      brachytherapy (PHDRB) and external beam irradiation (EBRT). PATIENT AND METHODS:
      Patients (n=166) enrolled in several PHDRB prospective studies conducted at the
      University of Navarre were analyzed. PHDRB was given to total doses of 16 Gy/4
      b.i.d. or 24 Gy/6 b.i.d. treatments for negative or close/positive margins along
      with 45Gy of EBRT. RESULTS: After a median followup of 7.4 years (range, 3-12+),
      50 patients have failed and 116 remain controlled at last followup. Tumor size,
      with a cutoff point set at 3cm (p=0.041) and margin status (positive and <1mm vs.
      negative >=1mm, p=0.0001) were independent predictors of locoregional control.
      These two parameters were used to develop a four-tiered, hierarchical scoring
      system that stratified patients into low-risk (negative >=1mm margins and size
      <=3cm), intermediate-risk (negative >=1mm margins, and size >3cm), high-risk
      (positive and <1mm margins and size <=3cm), and very high-risk categories
      (positive and <1mm margins and size >3cm). This classification yields 5-year
      locoregional control rates of 92.3%, 78.0%, 65.5%, and 48.0% for low-,
      intermediate-, high-, and very high-risk categories, respectively. The predictive
      ability of the model is highly significant (p=0.0001) with an area under the
      curve of 0.72 (0.64-0.81). CONCLUSIONS: The risk of locoregional failure after
      combined surgical resection, PHDRB, and EBRT is mainly determined by the number
      of residual clonogens, which is inversely proportional to the status of the
      surgical margins and directly related to the size of the resected tumor. These
      two parameters generate a four-tiered predictive model that seems to be valid for
      a number of different common tumors and clinical settings.

PMID- 24295965
TI  - Salvage brachytherapy for recurrent prostate cancer.
AB  - PURPOSE: To evaluate the role of salvage prostate brachytherapy for locally
      recurrent prostate cancer after external beam radiation alone. METHODS AND
      MATERIALS: Sixty-nine consecutive patients treated with salvage brachytherapy
      after a local failure were analyzed. All patients were found to have pathologic
      proven recurrent prostate cancer at least 2 years after initial therapy and no
      regional or distant disease on imaging studies. Pd-103 was used with a prescribed
      pD90 of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as
      part of their salvage therapy. Patients whose prostate-specific antigen >5.0
      ng/mL while on AS were considered to have castration resistant prostate cancer
      (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to
      have delayed therapy. Patients retreated within 5 years after their initial
      treatment were considered to have early failures. RESULTS: Total median followup
      after salvage therapy was 5.0 years (0.6-13.7). From the date of salvage, 5-year
      biochemical control for low-risk patients was 85.6%, intermediate-risk patients
      74.8%, and high-risk patients 66%. Five-year biochemical control was 73.8% for
      non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases,
      early treatment after failure vs. delayed treatment was significantly better
      (p<0.05). Chronic adverse events were seen in few patients, with genitourinary
      Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3
      or higher toxicities. CONCLUSIONS: A subset of failures after definitive
      radiation is local in nature, and excellent control is possible with salvage
      brachytherapy.

PMID- 24295966
TI  - Recrystallization improves the mechanical properties of sintered electrospun
      polycaprolactone.
AB  - BACKGROUND: Resorbable electrospun polycaprolactone (PCL) scaffolds for tissue
      reconstruction can provide physicians with an "off the shelf" product tailored to
      the patient's specific tissue architecture. However, many tissue-engineering
      platforms do not possess the necessary long-term mechanical stability needed to
      properly support tissue development. OBJECTIVE: Sintering has been explored as a
      means of altering the properties of electrospun PCL. However, crystallinity
      driven changes in mechanical properties following thermal treatment have not been
      previously investigated. METHODS: PCL nanofibers were produced by electrospinning
      and subsequently thermally sintered (at 55, 56 and 58 degrees C) to enhance their
      long-term mechanical integrity in response to representative biological milieux.
      RESULTS: Scaffolds initially sintered at 56 degrees C displayed 6-fold increases
      in compressive strength and 3-fold increases in modulus, while displaying 10-fold
      increases in energy dissipation with increasing sintering temperature. Sintering
      just below the Tm resulted in amorphization of the 55 degrees C sample as
      indicated by the 20-fold lower XRD peak intensities. Although crystallinity is
      suppressed, the polymer chains likely retain chain alignment from electrospinning
      and are apparently highly susceptible to recrystallization. After only 1d PBS
      exposure, the 55 degrees C samples recover a substantial fraction of the as-spun
      crystallinity; 7d of exposure fully restores as-spun peak intensities. The
      mechanical properties of all three (55, 56, or 58 degrees C) scaffolds displayed
      peak values of compressive strength and modulus following 7d exposure.
      CONCLUSION: In contrast with the current state-of-the-art which assumes that
      tissue engineering scaffolds only grow weaker following exposure, in these
      scaffolds maximum values of compressive strength and modulus were observed after
      7d of aqueous immersion. This suggests that polymeric recrystallization can be
      used to increase or optimize mechanical properties in vitro/in vivo. Scaffolds
      that increase their mechanical integrity during biological exposures constitute a
      new pathway enabling clinical advances.

PMID- 24295967
TI  - Biomechanical measurements of cortical screw purchase in five types of human and
      artificial humeri.
AB  - Humerus shaft fracture fixation is largely dependent on cortical screw purchase
      in host bone. Only 2 prior studies assessed cortical screw purchase in human
      humeral shafts, but were of very limited scope and did not fully assess humerus
      material properties. Also, no studies evaluated the human dried or artificial
      humeri both commercially available from Sawbones. Vashon, WA, USA. Therefore,
      present authors measured cortical screw purchase in human fresh-frozen (FF)
      (n=19), human embalmed (EM) (n=18), human dried (DR) (n=14), artificial "normal"
      (AN) (n=13), and artificial "osteoporotic" (AO) (n=13) humeri. Each humerus had 2
      bicortical screws of 3.5-mm diameter inserted 20mm apart through the shaft's
      anterior and posterior cortices. Absolute force, displacement, and energy for
      screw-bone interface failure were measured by screw pullout tests, afterwhich
      data were normalized by total surface area engaged at the screw-bone interface.
      For absolute force, AN humeri reached a higher load than EM (p=0.001) and AO
      (p<0.001) humeri, whilst AN humeri achieved lower normalized force than DR humeri
      (p=0.018). For absolute displacement, AO humeri achieved a lower level than FF
      humeri (p=0.013), whilst for normalized displacement AN humeri had lower levels
      than all other groups (p<=0.005) and AO humeri had lower values than EM humeri
      (p=0.029). For absolute and normalized energy, there were no statistical
      differences (p>=0.066). Human bone mineral density (BMD) ranged from 0.7 to
      1.8g/cm(2) and was linearly correlated to screw pullout parameters in 14 of 18
      cases (R=0.61 to 0.96), whilst humerus age was not. Consequently, it is
      recommended that human fresh-frozen, human embalmed, and human dried humeri can
      be used interchangeably for cortical screw purchase, since they were
      statistically equivalent for all comparisons. However, artificial humeri were
      involved in all statistical differences observed and, thus, may not replicate
      cortical screw purchase in human humeri. To date, this is the most comprehensive
      study on cortical screw purchase in human and artificial humeral shafts. 

PMID- 24295969
TI  - First report of macrolide resistance in a Mycoplasma pneumoniae isolate causing
      community-acquired pneumonia in Spain.

PMID- 24295968
TI  - Estimation of intracellular concentration of stavudine triphosphate in HIV
      infected children given a reduced dose of 0.5 milligrams per kilogram twice
      daily.
AB  - The antiviral efficacy of stavudine depends on the trough concentration of its
      intracellular metabolite, stavudine-triphosphate (d4T-TP), while the degree of
      stavudine's mitochondrial toxicity depends on its peak concentration. Rates of
      mitochondrial toxicity are high when stavudine is used at the current standard
      pediatric dose (1 mg/kg twice daily [BID]). Evidence from adult work suggests
      that half of the original standard adult dose (i.e., 20 mg BID) may be equally
      effective, with markedly less mitochondrial toxicity. We present a population
      pharmacokinetic model to predict intracellular d4T-TP concentrations in pediatric
      HIV-infected patients administered a dose of 0.5 mg/kg BID. Our model predicted
      that the reduced pediatric dose would result in a trough intracellular d4T-TP
      concentration above that of the reduced 20-mg adult dose and a peak concentration
      below that of the 20-mg adult dose. The simulated pediatric intracellular d4T-TP
      at 0.5 mg/kg BID resulted in median peak and trough values of approximately 23.9
      fmol/10(6) cells (95% prediction interval [PI], 14.2 to 41 fmol/10(6) cells) and
      14.8 fmol/10(6) cells (95% PI, 7.2 to 31 fmol/10(6) cells), respectively. The
      peak and trough concentrations resulting from a 20-mg BID adult dose were 28.4
      fmol/10(6) cells (95% PI, 17.3 to 45.5 fmol/10(6) cells) and 13 fmol/10(6) cells
      (95% PI, 6.8 to 28.6 fmol/10(6) cells), respectively. Halving the current
      standard pediatric dose should therefore not compromise antiviral efficacy, while
      markedly reducing mitochondrial toxicity. 

PMID- 24295970
TI  - First report of a Salmonella enterica serovar typhimurium isolate with
      carbapenemase (KPC-2) in Colombia.

PMID- 24295971
TI  - First report of OXA-23-mediated carbapenem resistance in sequence type 2
      multidrug-resistant Acinetobacter baumannii associated with urinary tract
      infection in a cat.

PMID- 24295972
TI  - Extended-spectrum-beta-lactamase-producing Escherichia coli as intestinal
      colonizers in the German community.
AB  - We determined the presence of extended-spectrum-beta-lactamase (ESBL)-producing
      Escherichia coli among 3,344 study participants from the German community.
      Intestinal colonization was detected in 211 persons (6.3%), without significant
      differences among the different age groups. The majority (95.2%) of isolates
      harbored CTX-M-type ESBL, with CTX-M-15 (46%) and CTX-M-1 (24.2%) as the most
      common types. The finding of ESBL producers and one isolate additionally
      producing carbapenemase OXA-244 indicates a risk of dissemination of resistant
      bacteria outside the hospitals. 

PMID- 24295973
TI  - Paradoxical growth of Candida albicans in the presence of caspofungin is
      associated with multiple cell wall rearrangements and decreased virulence.
AB  - In the last decade, echinocandins have emerged as an important family of
      antifungal drugs because of their fungicidal activity against Candida spp.
      Echinocandins inhibit the enzyme beta-1,3-d-glucan synthase, encoded by the FKS
      genes, and resistance to echinocandins is associated with mutations in this gene.
      In addition, echinocandin exposure can produce paradoxical growth, defined as the
      ability to grow at high antifungal concentrations but not at intermediate
      concentrations. In this work, we have demonstrated that paradoxical growth of
      Candida albicans in the presence of caspofungin is not due to antifungal
      degradation or instability. Media with high caspofungin concentrations recovered
      from wells where C. albicans showed paradoxical growth inhibited the growth of a
      Candida krusei reference strain. Cells exhibiting paradoxical growth at high
      caspofungin concentrations showed morphological changes such as enlarged size,
      abnormal septa, and absence of filamentation. Chitin content increased from the
      MIC to high caspofungin concentrations. Despite the high chitin levels, around
      23% of cells died after treatment with caspofungin, indicating that chitin is
      required but not sufficient to protect the cells from the fungicidal effect of
      caspofungin. Moreover, we found that after paradoxical growth, beta-1,3-glucan
      was exposed at the cell wall surface. Cells grown at high caspofungin
      concentrations had decreased virulence in the invertebrate host Galleria
      mellonella. Cells grown at high caspofungin concentrations also induced a
      proinflammatory response in murine macrophages compared to control cells. Our
      work highlights important aspects about fungal adaptation to caspofungin, and
      although this adaptation is associated with reduced virulence, the clinical
      implications remain to be elucidated. 

PMID- 24295974
TI  - Raltegravir has a low propensity to cause clinical drug interactions through
      inhibition of major drug transporters: an in vitro evaluation.
AB  - Raltegravir (RAL) is a human immunodeficiency virus type 1 (HIV-1) integrase
      inhibitor approved to treat HIV infection in adults in combination with other
      antiretrovirals. The potential of RAL to cause transporter-related drug-drug
      interactions (DDIs) as an inhibitor has not been well described to date. In this
      study, a series of in vitro experiments were conducted to assess the inhibitory
      effects of RAL on major human drug transporters known to be involved in
      clinically relevant drug interactions, including hepatic and renal uptake
      transporters and efflux transporters. For hepatic uptake transporters, RAL showed
      no inhibition of organic anion-transporting polypeptide 1B1 (OATP1B1), weak
      inhibition of OATP1B3 (40% inhibition at 100 MUM), and no inhibition of organic
      cation transporter 1 (OCT1). Studies of renal uptake transporters showed that RAL
      inhibited organic anion transporters 1 and 3 (OAT1 and OAT3) with 50% inhibitory
      concentrations (IC50s) (108 MUM and 18.8 MUM, respectively) well above the
      maximum concentration of drug in plasma (Cmax) at the clinical 400-mg dose and
      did not inhibit organic cation transporter 2 (OCT2). As for efflux transporters,
      RAL did not inhibit breast cancer resistance protein (BCRP) and showed weak
      inhibition of multidrug and toxin extrusion protein 1 (MATE1) (52% inhibition at
      100 MUM) and MATE2-K (29% inhibition at 100 MUM). These studies indicate that at
      clinically relevant exposures, RAL does not inhibit or only weakly inhibits
      hepatic uptake transporters OATP1B1, OATP1B3, and OCT1, renal uptake transporters
      OCT2, OAT1, and OAT3, as well as efflux transporters BCRP, MATE1, and MATE2-K.
      The propensity for RAL to cause DDIs via inhibition of these transporters is
      therefore considered low. 

PMID- 24295975
TI  - Antiviral activity of (+)-rutamarin against Kaposi's sarcoma-associated
      herpesvirus by inhibition of the catalytic activity of human topoisomerase II.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of several
      AIDS-associated malignancies, including Kaposi's sarcoma (KS), primary effusion
      lymphoma (PEL), and multicentric Castleman's disease (MCD). Its lytic replication
      cycle has been proven to be critical for the pathogenesis of KSHV-associated
      diseases. In KS lesions, lytic viral replication, production of virion particles,
      and reinfection of endothelial cells are essential to sustain the population of
      infected cells that otherwise would be quickly lost as spindle cells divide.
      Thus, antivirals that block KSHV replication could be a strategy in the treatment
      of KSHV-associated diseases. However, there is no effective anti-KSHV drug
      currently available. Our previous work showed that human topoisomerase II (Topo
      II) is indispensable for KSHV lytic replication and is suggested to be an
      effective target for antiviral drugs. Here, we report the discovery and
      characterization of a novel catalytic inhibitor of human Topo IIalpha, namely,
      (+)-rutamarin. The binding mode of (+)-rutamarin to the ATPase domain of human
      Topo IIalpha was established by docking and validated by molecular dynamics (MD)
      simulations. More importantly, (+)-rutamarin efficiently inhibits KSHV lytic DNA
      replication in BCBL-1 cells with a half-maximal inhibitory concentration (IC50)
      of 1.12 MUM and blocks virion production with a half-maximal antiviral effective
      concentration (EC50) of 1.62 MUM. It possesses low cytotoxicity, as indicated by
      the selectivity index (SI) of 84.14. This study demonstrated great potential for
      (+)-rutamarin to become an effective drug for treatment of human diseases
      associated with KSHV infection. 

PMID- 24295976
TI  - Image-based 384-well high-throughput screening method for the discovery of
      skyllamycins A to C as biofilm inhibitors and inducers of biofilm detachment in
      Pseudomonas aeruginosa.
AB  - To date, most antibiotics have primarily been developed to target bacteria in the
      planktonic state. However, biofilm formation allows bacteria to develop tolerance
      to antibiotics and provides a mechanism to evade innate immune systems.
      Therefore, there is a significant need to identify small molecules to prevent
      biofilm formation and, more importantly, to disperse or eradicate preattached
      biofilms, which are a major source of bacterial persistence in nosocomial
      infections. We now present a modular high-throughput 384-well image-based
      screening platform to identify Pseudomonas aeruginosa biofilm inhibitors and
      dispersal agents. Biofilm coverage measurements were accomplished using non-z
      stack epifluorescence microscopy to image a constitutively expressing green
      fluorescent protein (GFP)-tagged strain of P. aeruginosa and quantified using an
      automated image analysis script. Using the redox-sensitive dye XTT, bacterial
      cellular metabolic activity was measured in conjunction with biofilm coverage to
      differentiate between classical antibiotics and nonantibiotic biofilm
      inhibitors/dispersers. By measuring biofilm coverage and cellular activity, this
      screen identifies compounds that eradicate biofilms through mechanisms that are
      disparate from traditional antibiotic-mediated biofilm clearance. Screening of
      312 natural-product prefractions identified the cyclic depsipeptide natural
      products skyllamycins B and C as nonantibiotic biofilm inhibitors with 50%
      effective concentrations (EC50s) of 30 and 60 MUM, respectively. Codosing
      experiments of skyllamycin B and azithromycin, an antibiotic unable to clear
      preattached biofilms, demonstrated that, in combination, these compounds were
      able to eliminate surface-associated biofilms and depress cellular metabolic
      activity. The skyllamycins represent the first known class of cyclic depsipeptide
      biofilm inhibitors/dispersers. 

PMID- 24295978
TI  - Detection of carbapenemase-producing bacteria by using an ultra-performance
      liquid chromatography-tandem mass spectrometry method.
AB  - The emergence of carbapenemase-producing bacteria poses a new challenge in the
      management of antibiotic therapies for patients. This report describes a new
      method using ultra-performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS) for rapid detection of carbapenemase activity in enterobacteria,
      Pseudomonas aeruginosa, and Acinetobacter baumannii. In a panel of 78 isolates,
      including 41 carbapenemase-producing strains, the ULPC-MS/MS assay showed 100%
      agreement with molecular characterization, whereas six carbapenemase-producing
      isolates were not detected by the modified Hodge test. 

PMID- 24295977
TI  - Assessment of an anti-alpha-toxin monoclonal antibody for prevention and
      treatment of Staphylococcus aureus-induced pneumonia.
AB  - Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of
      Staphylococcus aureus. We previously identified a monoclonal antibody (MAb)
      against AT that reduced disease severity in a mouse dermonecrosis model. Here, we
      evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of
      S. aureus pneumonia. Passive immunization with LC10 increased survival and
      reduced bacterial numbers in the lungs and kidneys of infected mice and showed
      protection against diverse S. aureus clinical isolates. The lungs of S. aureus
      infected mice exhibited bacterial pneumonia, including widespread inflammation,
      whereas the lungs of mice that received LC10 exhibited minimal inflammation and
      retained healthy architecture. Consistent with reduced immune cell infiltration,
      LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine
      and chemokine levels in the bronchoalveolar lavage fluid than did those of the
      control animals. This reduction in inflammation and damage to the LC10-treated
      animals resulted in reduced vascular protein leakage and CO2 levels in the blood.
      LC10 was also assessed for its therapeutic activity in combination with
      vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or
      linezolid resulted in a significant increase (P < 0.05) in survival relative to
      the monotherapies and was deemed additive to synergistic by isobologram analysis.
      Consistent with improved survival, the lungs of animals treated with antibiotic
      plus LC10 exhibited less inflammatory tissue damage than those that received
      monotherapy. These data provide insight into the mechanisms of protection
      provided by AT inhibition and support AT as a promising target for
      immunoprophylaxis or adjunctive therapy against S. aureus pneumonia. 

PMID- 24295979
TI  - Oxacillin alters the toxin expression profile of community-associated methicillin
      resistant Staphylococcus aureus.
AB  - The emergence of community-associated methicillin-resistant Staphylococcus aureus
      (CA-MRSA) is a growing cause for concern. These strains are more virulent than
      health care-associated MRSA (HA-MRSA) due to higher levels of toxin expression.
      In a previous study, we showed that the high-level expression of PBP2a, the
      alternative penicillin binding protein encoded by the mecA gene on type II
      staphylococcal cassette chromosome mec (SCCmec) elements, reduced toxicity by
      interfering with the Agr quorum sensing system. This was not seen in strains
      carrying the CA-MRSA-associated type IV SCCmec element. These strains express
      significantly lower levels of PBP2a than the other MRSA type, which may explain
      their relatively high toxicity. We hypothesized that as oxacillin is known to
      increase mecA expression levels, it may be possible to attenuate the toxicity of
      CA-MRSA by using this antibiotic. Subinhibitory oxacillin concentrations induced
      PBP2a expression, repressed Agr activity, and, as a consequence, decreased phenol
      soluble modulin (PSM) secretion by CA-MRSA strains. However, consistent with
      other studies, oxacillin also increased the expression levels of alpha-toxin and
      Panton-Valentine leucocidin (PVL). The net effect of these changes on the ability
      to lyse diverse cell types was tested, and we found that where the PSMs and alpha
      toxin are important, oxacillin reduced overall lytic activity, but where PVL is
      important, it increased lytic activity, demonstrating the pleiotropic effect of
      oxacillin on toxin expression by CA-MRSA. 

PMID- 24295980
TI  - Functional linkage between genes that regulate osmotic stress responses and
      multidrug resistance transporters: challenges and opportunities for antibiotic
      discovery.
AB  - All cells need to protect themselves against the osmotic challenges of their
      environment by maintaining low permeability to ions across their cell membranes.
      This is a basic principle of cellular function, which is reflected in the
      interactions among ion transport and drug efflux genes that have arisen during
      cellular evolution. Thus, upon exposure to pore-forming antibiotics such as
      amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common
      resistance genes to protect themselves from added osmotic challenges. These genes
      share pathway interactions with the various types of multidrug resistance (MDR)
      transporter genes, which both preserve the native lipid membrane composition and
      at the same time eliminate disruptive hydrophobic molecules that partition
      excessively within the lipid bilayer. An increased understanding of the
      relationships between the genes (and their products) that regulate osmotic stress
      responses and MDR transporters will help to identify novel strategies and targets
      to overcome the current stalemate in drug discovery. 

PMID- 24295981
TI  - An NF-kappaB-based high-throughput screen identifies piericidins as inhibitors of
      the Yersinia pseudotuberculosis type III secretion system.
AB  - The type III secretion system (T3SS) is a bacterial appendage used by dozens of
      Gram-negative pathogens to subvert host defenses and cause disease, making it an
      ideal target for pathogen-specific antimicrobials. Here, we report the discovery
      and initial characterization of two related natural products with T3SS-inhibitory
      activity that were derived from a marine actinobacterium. Bacterial extracts
      containing piericidin A1 and the piericidin derivative Mer-A 2026B inhibited
      Yersinia pseudotuberculosis from triggering T3SS-dependent activation of the host
      transcription factor NF-kappaB in HEK293T cells but were not toxic to mammalian
      cells. As the Yersinia T3SS must be functional in order to trigger NF-kappaB
      activation, these data indicate that piericidin A1 and Mer-A 2026B block T3SS
      function. Consistent with this, purified piericidin A1 and Mer-A 2026B dose
      dependently inhibited translocation of the Y. pseudotuberculosis T3SS effector
      protein YopM inside CHO cells. In contrast, neither compound perturbed bacterial
      growth in vitro, indicating that piericidin A1 and Mer-A 2026B do not function as
      general antibiotics in Yersinia. In addition, when Yersinia was incubated under
      T3SS-inducing culture conditions in the absence of host cells, Mer-A 2026B and
      piericidin A1 inhibited secretion of T3SS cargo as effectively as or better than
      several previously described T3SS inhibitors, such as MBX-1641 and aurodox. This
      suggests that Mer-A 2026B and piericidin A1 do not block type III secretion by
      blocking the bacterium-host cell interaction, but rather inhibit an earlier
      stage, such as T3SS needle assembly. In summary, the marine-derived natural
      products Mer-A 2026B and piericidin A1 possess previously uncharacterized
      activity against the bacterial T3SS. 

PMID- 24295982
TI  - Phenotypic profiling of antibiotic response signatures in Escherichia coli using
      Raman spectroscopy.
AB  - Identifying the mechanism of action of new potential antibiotics is a necessary
      but time-consuming and costly process. Phenotypic profiling has been utilized
      effectively to facilitate the discovery of the mechanism of action and molecular
      targets of uncharacterized drugs. In this research, Raman spectroscopy was used
      to profile the phenotypic response of Escherichia coli to applied antibiotics.
      The use of Raman spectroscopy is advantageous because it is noninvasive, label
      free, and prone to automation, and its results can be obtained in real time. In
      this research, E. coli cultures were subjected to three times the MICs of 15
      different antibiotics (representing five functional antibiotic classes) with
      known mechanisms of action for 30 min before being analyzed by Raman spectroscopy
      (using a 532-nm excitation wavelength). The resulting Raman spectra contained
      sufficient biochemical information to distinguish between profiles induced by
      individual antibiotics belonging to the same class. The collected spectral data
      were used to build a discriminant analysis model that identified the effects of
      unknown antibiotic compounds on the phenotype of E. coli cultures. Chemometric
      analysis showed the ability of Raman spectroscopy to predict the functional class
      of an unknown antibiotic and to identify individual antibiotics that elicit
      similar phenotypic responses. Results of this research demonstrate the power of
      Raman spectroscopy as a cellular phenotypic profiling methodology and its
      potential impact on antibiotic drug development research. 

PMID- 24295983
TI  - Pathogenicity of clinical Acinetobacter baumannii isolates in a Galleria
      mellonella host model according to bla(OXA-40) gene and epidemiological outbreak
      status.
AB  - Clinical studies have suggested that blaOXA-40-positive Acinetobacter baumannii
      isolates are associated with poor patient outcomes; however, reasons for
      unfavorable outcomes are difficult to discern in clinical studies. The objective
      of this study was to assess the virulence of carbapenem-resistant A. baumannii
      according to blaOXA-40 and epidemiological outbreak status in a Galleria
      mellonella model. Eight isolates of A. baumannii were studied. Nonoutbreak
      isolates and blaOXA-40-negative isolates more rapidly killed infected G.
      mellonella (P < 0.01). 

PMID- 24295984
TI  - Nucleotide sequence analysis of integrative conjugative element Tn5253 of
      Streptococcus pneumoniae.
AB  - Conjugative transposon Tn5253, an integrative conjugative element (ICE) of
      Streptococcus pneumoniae carrying the cat and tet(M) genes, was shown to be
      64,528 bp in size and to contain 79 open reading frames, of which only 38 could
      be annotated. Two distinct genetic elements were found integrated into Tn5253:
      Tn5251 (18,033 bp), of the Tn916-Tn1545 family of ICEs, and Omegacat(pC194)
      (7,627 bp), which could not conjugate but was capable of intracellular mobility
      by excision, circularization, and integration by homologous recombination. The
      highest conjugation frequency of Tn5253 was observed when Streptococcus pyogenes
      was the donor (6.7 * 10(-3) transconjugants/donor). 

PMID- 24295985
TI  - In vitro and in vivo antibacterial activities of omadacycline, a novel
      aminomethylcycline.
AB  - Omadacycline is the first intravenous and oral 9-aminomethylcycline in clinical
      development for use against multiple infectious diseases including acute
      bacterial skin and skin structure infections (ABSSSI), community-acquired
      bacterial pneumonia (CABP), and urinary tract infections (UTI). The comparative
      in vitro activity of omadacycline was determined against a broad panel of Gram
      positive clinical isolates, including methicillin-resistant Staphylococcus aureus
      (MRSA), vancomycin-resistant Enterococcus (VRE), Lancefield groups A and B beta
      hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae (PRSP), and
      Haemophilus influenzae (H. influenzae). The omadacycline MIC90s for MRSA, VRE,
      and beta-hemolytic streptococci were 1.0 MUg/ml, 0.25 MUg/ml, and 0.5 MUg/ml,
      respectively, and the omadacycline MIC90s for PRSP and H. influenzae were 0.25
      MUg/ml and 2.0 MUg/ml, respectively. Omadacycline was active against organisms
      demonstrating the two major mechanisms of resistance, ribosomal protection and
      active tetracycline efflux. In vivo efficacy of omadacycline was demonstrated
      using an intraperitoneal infection model in mice. A single intravenous dose of
      omadacycline exhibited efficacy against Streptococcus pneumoniae, Escherichia
      coli, and Staphylococcus aureus, including tet(M) and tet(K) efflux-containing
      strains and MRSA strains. The 50% effective doses (ED50s) for Streptococcus
      pneumoniae obtained ranged from 0.45 mg/kg to 3.39 mg/kg, the ED50s for
      Staphylococcus aureus obtained ranged from 0.30 mg/kg to 1.74 mg/kg, and the ED50
      for Escherichia coli was 2.02 mg/kg. These results demonstrate potent in vivo
      efficacy including activity against strains containing common resistance
      determinants. Omadacycline demonstrated in vitro activity against a broad range
      of Gram-positive and select Gram-negative pathogens, including resistance
      determinant-containing strains, and this activity translated to potent efficacy
      in vivo. 

PMID- 24295988
TI  - An insatiable advocate.

PMID- 24295986
TI  - Efficacy and safety of danoprevir-ritonavir plus peginterferon alfa-2a-ribavirin
      in hepatitis C virus genotype 1 prior null responders.
AB  - Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves
      high sustained virologic response (SVR) rates in combination with peginterferon
      alfa-2a-ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This
      study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus
      peginterferon alfa-2a-ribavirin in G1-infected prior peginterferon-ribavirin null
      responders. Null responders (<2-log10 reduction in HCV RNA level at week 12) were
      given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100
      mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a-ribavirin for 12 weeks. All
      patients achieving an early virologic response (EVR; >=2-log10 decrease in HCV
      RNA by week 12) continued treatment with peginterferon alfa-2a-ribavirin; those
      without an EVR discontinued all study drugs. Twenty-four prior null responders
      were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were
      infected with G1a. Ninety-six percent of patients had an IL28B non-CC genotype. A
      sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in
      67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%)
      patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b
      patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K
      was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated.
      Two patients withdrew prematurely from study medications due to adverse events.
      Two serious adverse events were reported; both occurred after completion of DNVr
      therapy and were considered unrelated to treatment. No grade 3 or 4 alanine
      aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a
      ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders
      and was well tolerated. (This study has been registered at ClinicalTrials.gov
      under registration no. NCT01185860.). 

PMID- 24295989
TI  - Madjid Samii: neurosurgeon of the year 2013.

PMID- 24295987
TI  - Subjective well-being measures for children were developed within the PROMIS
      project: presentation of first results.
AB  - OBJECTIVES: The aims of this Patient Reported Outcome Measurement Information
      System (PROMIS) study were to (1) conceptualize children's subjective well-being
      (SWB) and (2) produce item pools with excellent content validity for calibration
      and use in computerized adaptive testings (CATs). STUDY DESIGN AND SETTING:
      Children's SWB was defined through semistructured interviews with experts,
      children (aged 8-17 years), parents, and a systematic literature review to
      identify item concepts comprehensively covering the full spectrum of SWB. Item
      concepts were transformed into item expressions and evaluated for
      comprehensibility using cognitive interviews, reading level analysis, and
      translatability review. RESULTS: Children's SWB comprises affective (positive
      affect) and global evaluation components (life satisfaction). Input from experts,
      children, parents, and the literature indicated that the eudaimonic dimension of
      SWB-that is, a sense of meaning and purpose-could be evaluated. Item pools for
      life satisfaction (56 items), positive affect (53 items), and meaning and purpose
      (55 items) were produced. Small differences in comprehensibility of some items
      were observed between children and adolescents. CONCLUSION: The SWB measures for
      children are the first to assess both the hedonic and eudaimonic aspects of SWB.
      Both children and youth seem to understand the concepts of a meaningful life,
      optimism, and goal orientation.

PMID- 24295990
TI  - 2013 neurosurgeon of the year: a personal statement.

PMID- 24295991
TI  - Madjid Samii: "A la Memoire d'un Grand Artiste".

PMID- 24295993
TI  - Madjid Samii, neurosurgeon of the year.

PMID- 24295992
TI  - "Quidquid agis prudenter agas et respice finem"--whatever you do, do it wisely
      and consider the end.

PMID- 24295994
TI  - Madjid Samii, a star and a friend.

PMID- 24295995
TI  - Madjid Samii: a life in the service of neurosurgery; a life in the service of
      mankind.

PMID- 24295996
TI  - Professor Madjid Samii.

PMID- 24295997
TI  - Madjid Samii.

PMID- 24295998
TI  - Madjid Samii: neurosurgeon of the year.

PMID- 24295999
TI  - Neurosurgeon of the year.

PMID- 24296000
TI  - The man with the Midas touch.

PMID- 24296001
TI  - Madjid Samii, neurosurgeon of the year 2013.

PMID- 24296002
TI  - Madjid Samii--neurosurgeon of the year.

PMID- 24296003
TI  - Madjid Samii: master surgeon, world leader.

PMID- 24296004
TI  - Prof. Samii, neurosurgeon of the year.

PMID- 24296005
TI  - Madjid Samii: a visionary, creative man and a world neurosurgery leader.

PMID- 24296006
TI  - Madjid Samii.

PMID- 24296007
TI  - My reflections on professor Madjid Samii.

PMID- 24296008
TI  - Short term inhalation toxicity of a liquid aerosol of glutaraldehyde-coated
      CdS/Cd(OH)2 core shell quantum dots in rats.
AB  - Quantum dots exhibit extraordinary optical and mechanical properties, and the
      number of their applications is increasing. In order to investigate a possible
      effect of coating on the inhalation toxicity of previously tested non-coated
      CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the
      lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+)
      was present as impurity), 6h/d for 5 consecutive days. Cd content was determined
      in organs and excreta after the end of exposure and three weeks thereafter.
      Toxicity was determined by examination of broncho-alveolar lavage fluid and
      microscopic evaluation of the entire respiratory tract. There was no evidence for
      translocation of particles from the respiratory tract. Evidence of a minimal
      inflammatory process was observed by examination of broncho-alveolar lavage
      fluid. Microscopically, minimal to mild epithelial alteration was seen in the
      larynx. The effects observed with coated quantum dots, non-coated quantum dots
      and CdCl2 were comparable, indicating that quantum dots elicited no significant
      effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds
      with larger particle size tested at similarly low concentrations, quantum dots
      caused much less pronounced toxicological effects. Therefore, the present data
      show that small particle sizes with corresponding high surfaces are not the only
      factor triggering the toxic response or translocation. 

PMID- 24296010
TI  - Complete genotype constellation of human rotavirus group A circulating in
      Thailand, 2008-2011.
AB  - This study has identified diverse and re-assorted group A rotavirus (RVA) strains
      by sequence and phylogenetic analysis of the 11 genomic segments. The 22 cases
      investigated in this study were collected from children with diarrhea between
      2008 and 2011. The RVA genomic constellations identified in this study were
      identified as G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 22.7% (5/22); G2-P[4]-I2-R2-C2
      M2-A2-N2-T2-E2-H2 27.3% (6/22); G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 18.2% (4/22);
      G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H6 4.6% (1/22); G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1
      H1 9.1% (2/22); G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 4.6% (1/22) and G12-P[8]-I1
      R1-C1-M1-A1-N1-T1-E1-H1 13.6% (3/22). Two RVA strains, possessing a complete AU-1
      like genomic backbone, showed re-assortment for genes 3 and 11, revealing
      possible zoonotic re-assortment events between human and canine strains. In
      addition, one of the analyzed strains revealed a G12 specificity for VP7 in
      combination with a porcine-like P[6] VP4 and a complete Wa-like constellation.
      Continuous surveillance of rotavirus strains and their evolution may be useful
      for understanding the emergence of novel strains through interspecies genome re
      assortment between human and animal viruses. 

PMID- 24296009
TI  - Blood and exhaled air can be used for biomonitoring of hydrofluorocarbon
      exposure.
AB  - Various hydrofluorocarbons (HFCs) have replaced the ozone-depleting
      chlorofluorocarbons and hydrochlorofluorocarbons during the last decades. The
      objective of this study was to examine the usefulness of blood and breath for
      exposure biomonitoring of HFCs. We compared data on blood and exhaled air from a
      series of experiments where healthy volunteers were exposed to vapors of four
      commonly used HFCs; 1,1-difluoroethane, 1,1,1-trifluoroethane, 1,1,1,2
      tetrafluoroethane, and 1,1,1,3,3-pentafluoropropane. All four HFCs had similar
      toxicokinetic profiles in blood with a rapid initial increase and an apparent
      steady-state reached within a few minutes. For all HFCs, the inhalation uptake
      during exposure was low (less than 6%), most of which was exhaled post-exposure.
      No metabolism could be detected and only minor amounts were excreted unchanged in
      urine. The observed time courses in blood and breath were well described by
      physiologically-based pharmacokinetic (PBPK) modeling. Simulations of 8-h
      exposures show that the HFC levels in both blood and breath drop rapidly during
      the first minutes post-exposure, whereafter the decline is considerably slower
      and mainly reflects washout from fat tissues. We conclude that blood and exhaled
      air can be used for biological exposure monitoring. Samples should not be taken
      immediately at the end of shift but rather 20-30 min later.

PMID- 24296011
TI  - Evidence of substantial recombination among Trypanosoma cruzi II strains from
      Minas Gerais.
AB  - Due to the scarcity of evidence of sexuality in Trypanosoma cruzi, the causative
      agent of Chagas disease, it has been general accepted that the parasite
      reproduction is essentially clonal with infrequent genetic recombination. This
      assumption is mainly supported by indirect evidence, such as Hardy-Weinberg
      imbalances, linkage disequilibrium and a strong correlation between independent
      sets of genetic markers of T. cruzi populations. However, because the analyzed
      populations are usually isolated from different geographic regions, the
      possibility of population substructuring as generating these genetic marker
      imbalances cannot be eliminated. To investigate this possibility, we firstly
      compared the allele frequencies and haplotype networks using seven different
      polymorphic loci (two from mitochondrial and five from different nuclear
      chromosomes) in two groups of TcII strains: one including isolates obtained from
      different regions in Latin America and the other including isolates obtained only
      from patients of the Minas Gerais State in Brazil. Our hypothesis was that if the
      population structure is essentially clonal, Hardy-Weinberg disequilibrium and a
      sharp association between the clusters generated by analyzing independent markers
      should be observed in both strain groups, independent of the geographic origin of
      the samples. The results demonstrated that the number of microsatellite loci in
      linkage disequilibrium decreased from 4 to 1 when only strains from Minas Gerais
      were analyzed. Moreover, we did not observed any correlation between the clusters
      when analyzing the nuclear and mitochondrial loci, suggesting independent
      inheritance of these markers among the Minas Gerais strains. Besides, using a
      second subset of five physically linked microsatellite loci and the Minas Gerais
      strains, we could also demonstrate evidence of homologous recombination roughly
      proportional to the relative distance among them. Taken together, our results do
      not support a clonal population structure for T. cruzi, particularly in TcII,
      which coexists in the same geographical area, suggesting that genetic exchanges
      among these strains may occur more frequently than initially expected. 

PMID- 24296012
TI  - Synthesis and SAR study of a novel series of dopamine receptor agonists.
AB  - The synthesis of a novel series of dopamine receptor agonists are described as
      well as their in vitro potency and efficacy on dopamine D1 and D2 receptors. This
      series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a
      octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted in the synthesis of
      (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H
      naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D1 and D2 receptor
      profile similar to that of the most recently approved drug for Parkinson's
      disease, rotigotine.

PMID- 24296013
TI  - Synthesis and anticancer activities of thieno[3,2-d]pyrimidines as novel HDAC
      inhibitors.
AB  - A series of thieno[3,2-d]pyrimidines bearing a hydroxamic acid moiety as novel
      HDAC inhibitors were designed and synthesized. The structures of the new
      synthesized compounds were confirmed using IR, (1)H, (13)C NMR spectrum.
      Compounds 11-13 showed potent inhibitory activities against HDACs with IC50
      values at 0.38, 0.49 and 0.61 MUM. Most of target compounds displayed strong anti
      proliferative activity by a MTT assay on three human cancer cell lines including
      HCT-116, MCF-7 and HeLa. Compound 11, having potent inhibitory activities against
      HDACs, induced apoptosis and G2/M cell cycle arrest in HCT-116 cell line.

PMID- 24296014
TI  - Perioperative management of the patient with diabetes mellitus: update and
      overview.
AB  - Perioperative management of diabetic patients involves optimizing glycemic
      control and negotiating comorbidities to help reduce complications and obtain
      results on par with nondiabetics. These goals are usually achievable in the
      elective surgical setting, but they can be more difficult to control in urgent or
      emergent situations. Understanding and recognizing the comorbidities associated
      with diabetes is imperative for optimizing outcomes. Regulating hyperglycemia can
      reduce morbidity, mortality, and postoperative infections. Understanding the
      effects of cardiac and renal disease is also important. Taking a team approach in
      managing these complex patients leads to improved outcomes and is now considered
      the standard of care. 

PMID- 24296015
TI  - Diabetes mellitus and peripheral vascular disease: diagnosis and management.
AB  - Diabetes mellitus and peripheral artery disease are prevalent diseases throughout
      the world and often present simultaneously in the same patient, which has direct
      implications for their diagnosis and management. Refinements of existing and
      development of new diagnostic and treatment modalities are changing the
      management of these diseases. This article reviews the significant pathologic
      basis, history, and physical examination findings with respect to each disease
      and their presentation together. Advantages and disadvantages of different
      diagnostic modalities, including noninvasive studies and imaging technologies,
      are discussed. General medical management principles and indications, techniques,
      and efficacy of surgical and endovascular interventions are reviewed. 

PMID- 24296016
TI  - New modalities in the chronic ischemic diabetic foot management.
AB  - The diabetic population is increasing worldwide at a staggering rate. Diabetic
      foot ulcers are a major contributor to nontraumatic lower limb amputations and
      peripheral arterial disease is one of main contributing pathophysiologic causes
      of diabetic ulcers. The dire need to reduce complication and wound healing
      recovery period of the chronic ischemic diabetic foot (CIDF) is indispensable to
      limb salvage and improvement of quality of life of patients with CIDF. This
      article discusses newer modalities that have been proposed to improve CIDF
      efficiently, safely, and effectively either alone or as adjuvants to conventional
      therapy. 

PMID- 24296018
TI  - Current therapies for diabetic foot infections and osteomyelitis.
AB  - Treatment of the patient with a diabetic foot infection and underlying
      osteomyelitis is currently an evolving process, often complicated by neuropathy,
      peripheral vascular disease, and renal insufficiency. Understanding which
      patients require hospitalization, intravenous antibiotic therapy, and urgent
      operative intervention may ultimately prevent the spread of infection or major
      limb amputation. The treating surgeon should focus on accurate and early
      diagnosis, proper antibiosis, and appropriate surgical debridement to eradicate
      infection while preserving function with a plantar-grade foot. 

PMID- 24296017
TI  - Imaging of diabetic foot infections.
AB  - Complications from diabetic foot infections are a leading cause of nontraumatic
      lower-extremity amputations. Nearly 85% of these amputations result from an
      infected foot ulcer. Osteomyelitis is present in approximately 20% of diabetic
      foot infections. It is imperative that clinicians make quick and successful
      diagnoses of diabetic foot osteomyelitis (DFO) because a delay in treatment may
      lead to worsening outcomes. Imaging studies, such as plain films, bone scans,
      musculoskeletal ultrasound, computerized tomography scans, magnetic resonance
      imaging, and positron emission tomography scans, aid in the diagnosis. However,
      there are several mimickers of DFO, which present problems to making a correct
      diagnosis. 

PMID- 24296019
TI  - Offloading of the diabetic foot: orthotic and pedorthic strategies.
AB  - The diabetic foot is more susceptible than the non-diabetic foot to collapse.
      This frequently leads to bony prominences followed by ulceration. Offloading of
      areas of increased pressure is paramount to ulcer prevention and healing. Several
      devices and accommodations can aid practitioners in saving patients' extremities
      and allow them to ambulate. A team approach works best, and patient education is
      a must. Regular assessment and modifications are required for longevity of each
      device. In this article, different therapeutic options are detailed. A variety of
      presentations and situations are discussed and the authors' best tips for
      avoiding complications are offered. 

PMID- 24296020
TI  - Bioengineered alternative tissues.
AB  - Bioengineered alternative tissues (BATs) are heterogeneous processed materials
      used to aid in wound closure of diabetic foot ulcers. There has been significant
      progress in the development and clinical use of BATs in the last decade. BATs may
      be derived from an autograft, allograft, or xenograft source. They may be a
      single-layer material and consist of only an epidermal or dermal component or
      they may be bilayer, consisting of both epidermal and dermal components. The holy
      grail of tissue replacement has yet to be discovered. Nevertheless, if
      researchers and bioengineers can flip the switch to return cells to their
      prenatal period, this can be a breakthrough in cellular regeneration. 

PMID- 24296021
TI  - Partial foot amputations for salvage of the diabetic lower extremity.
AB  - Lower extremity infections are a common yet unfortunate complication of diabetes
      related ulcers often requiring surgical intervention. The main goals of surgical
      treatment consist of selecting the appropriate procedure to effectively eradicate
      nonsalvageable tissue, achieve primary healing, and maximize subsequent dynamic
      functionality. An overview of each partial foot amputation procedure is discussed
      with a focus on procedure selection as well as standard and advanced surgical
      techniques. The effective application of partial foot amputations in the high
      risk diabetic population can act to minimize the need for major proximal lower
      limb amputations. 

PMID- 24296022
TI  - The role of plastic surgery for soft tissue coverage of the diabetic foot and
      ankle.
AB  - The goal of wound healing is to obtain the best closure through the least morbid
      means. In the surgical treatment of the diabetic foot and ankle, the
      reconstructive foot and ankle surgeon is tasked with the challenge of repairing a
      variety of tissue defects. The decision for wound closure depends on the location
      of the wound and host factors. In order of increasing complexity, the clinician
      should consider the reconstruction decision ladder algorithm. Wound evaluation
      coupled with the knowledge of various closure techniques and their indications
      will arm the surgeon with the tools for a successful closure. 

PMID- 24296023
TI  - Charcot neuroarthropathy of the foot and ankle: diagnosis and management
      strategies.
AB  - This article reviews current literature discussing the etiology, pathophysiology,
      diagnosis and imaging, and conservative and surgical treatment of Charcot
      osteoarthropathy. The treatment of Charcot osteoarthropathy with concurrent
      osteomyelitis is also discussed. 

PMID- 24296024
TI  - Prosthetic options available for the diabetic lower limb amputee.
AB  - Although the rate of lower limb amputation in patients with diabetes is
      decreasing, amputation still remains a major complication of diabetes.
      Prosthetics have been long used to help amputees ambulate. The last decade has
      seen many advances in prostheses with the enhanced understanding of the mechanics
      of ambulation and improved use of technology. This review describes the different
      types of prosthetic options available for below knee, ankle, and foot amputees,
      emphasizing the latest advances in prosthetic design. 

PMID- 24296025
TI  - Medical and surgical management of the diabetic foot and ankle.

PMID- 24296026
TI  - Medical and surgical management of the diabetic foot and ankle.

PMID- 24296027
TI  - Predictive modeling studies for the ecotoxicity of ionic liquids towards the
      green algae Scenedesmus vacuolatus.
AB  - Hazardous potential of ionic liquids is becoming an issue of high concern with
      increasing application of these compounds in various industrial processes.
      Predictive toxicological modeling on ionic liquids provides a rational assessment
      strategy and aids in developing suitable guidance for designing novel analogues.
      The present study attempts to explore the chemical features of ionic liquids
      responsible for their ecotoxicity towards the green algae Scenedesmus vacuolatus
      by developing mathematical models using extended topochemical atom (ETA) indices
      along with other categories of chemical descriptors. The entire study has been
      conducted with reference to the OECD guidelines for QSAR model development using
      predictive classification and regression modeling strategies. The best models
      from both the analyses showed that ecotoxicity of ionic liquids can be decreased
      by reducing chain length of cationic substituents and increasing hydrogen bond
      donor feature in cations, and replacing bulky unsaturated anions with simple
      saturated moiety having less lipophilic heteroatoms. 

PMID- 24296028
TI  - Detection and analysis of neonicotinoids in river waters--development of a
      passive sampler for three commonly used insecticides.
AB  - Increasing and widespread use of neonicotinoid insecticides all over the world,
      together with their environmental persistence mean that surface and ground waters
      need to be monitored regularly for their residues. However, current multi-residue
      analytical methods for waters are inadequate for trace residue analysis of these
      compounds, while passive sampling devices are unavailable. A new method using
      UltraPerformance Liquid Chromatography provided good separation of the five most
      common neonicotinoid compounds, with limits of quantitation in the range 0.6
      1.0ng. The method was tested in a survey of rivers around Sydney (Australia),
      where 93% of samples contained two or more neonicotinoids in the range 0.06
      4.5MUgL(-1). Styrenedivinylbenzene-reverse phase sulfonated EmporeTM disks were
      selected as the best matrix for use in passive samplers. Uptake of clothianidin,
      imidacloprid and thiacloprid in a flow-through laboratory system for 3weeks was
      linear and proportional to their water concentrations over the range 1-10MUgL(
      1). Sampling rates of 8-15mLd(-1) were correlated to the hydrophobicity of the
      individual compounds. The passive samplers and analytical methods presented here
      can detect trace concentrations of neonicotinoids in water. 

PMID- 24296029
TI  - Effects of three kinds of organic acids on phosphorus recovery by magnesium
      ammonium phosphate (MAP) crystallization from synthetic swine wastewater.
AB  - P recovery from swine wastewater has become a great concern as a result of the
      high demand for P resources and its potential eutrophication effects on water
      ecosystems. The method of magnesium ammonium phosphate (MAP) crystallization was
      used to recover P from simulated swine wastewater, and the effects of three
      organic acids (citric acid, succinic acid and acetic acid) on P removal
      efficiency and rate at different pH values were investigated. The results
      indicated that the P removal efficiency was worst affected by citric acid in the
      optimal pH range of 9.0-10.5, followed by succinic acid and acetic acid, and the
      influencing extent of organic acids decreased with the increasing pH value. Due
      to the complexation between organic acid and Mg(2+)/NH4(+), all of three organic
      acids could inhibit the P removal rate at the beginning of the reaction, which
      showed positive correlation between the inhibition effects and the concentration
      of organic acids. The high concentration of citric acid could completely suppress
      the MAP crystallization reaction. Moreover, citric acid and succinic acid brought
      obvious effects on the morphology of the crystallized products. The experimental
      results also demonstrated that MAP crystals could be obtained in the presence of
      different kinds and concentrations of organic acids. 

PMID- 24296030
TI  - Diesel oil volatilization processes affected by selected porous media.
AB  - Volatilization plays an important role in attenuating petroleum products in
      contaminated soils. The objective of this study was to evaluate the influence of
      wind speed, vessel diameter and mean grain size of porous media on diesel oil
      volatilization. Experiments were conducted to investigate the volatilization
      behavior of diesel oil from porous media by weighing contaminated samples pre-
      and post-volatilization. Three selected field porous media materials were
      evaluated: Silty Clay Loam, Fine Sand, and Coarse Sand along with six individual
      sand fractions of the Coarse Sand. Results indicate that increasing wind speed
      accelerates the diesel oil volatilization process, especially for wind speeds
      below 2.10ms(-1). The low-carbon components of diesel oil volatilize more
      rapidly, with the effects of wind speed more pronounced on C10 to C15
      volatilization than on C16 and higher. The volatilization rate coefficient of
      diesel oil increases with decreasing mean grain size of porous media, and with
      increasing vessel diameter. A power function expressed the relationship with mean
      grain size. All processes (wind speed, vessel diameter, and mean grain size) were
      included in an equation which explained over 92% of the measured diesel oil
      volatilization rate coefficient variations for the experiments. Diesel oil
      volatilization appears to be boundary-layer regulated to some extent. 

PMID- 24296031
TI  - Application of ultrasound and quartz sand for the removal of disinfection
      byproducts from drinking water.
AB  - To the best of our knowledge, little information is available on the combined use
      of ultrasound (US) and quartz sand (QS) in the removal of disinfection byproducts
      (DBPs) from drinking water. This study investigates the removal efficiency for 12
      DBPs from drinking water by 20 kHz sonolytic treatment, QS adsorption, and their
      combination. Results indicate that DBPs with logKow<=1.12 could not be
      sonolysized; for logKow>=1.97, more than 20% removal efficiency was observed, but
      the removal efficiency was unrelated to logKow. DBPs containing a nitro group are
      more sensitive to US than those that comprise nitrile, hydrogen, and hydroxyl
      groups. Among the 12 investigated DBPs, 9 could be adsorbed by QS adsorption. The
      adsorption efficiency ranged from 12% for 1,1-dichloro-2-propanone to 80% for
      trichloroacetonitrile. A synergistic effect was found between the US and QS on
      DBPs removal, and all the 12 DBPs could be effectively removed by the combined
      use of US and QS. In the presence of US, part of the QS particles were corroded
      into small particles which play a role in increasing the number of cavitation
      bubbles and reducing cavitation bubble size and then improve the removal
      efficiency of DBPs. On the other hand, the presence of US enhances the DBP mass
      transfer rate to cavitation bubbles and quartz sand. In addition, sonolytic
      treatment led to a slight decrease of pH, and TOC values decreased under all the
      three treatment processes.

PMID- 24296032
TI  - Nuclear PI-PLCbeta1: an appraisal on targets and pathology.
AB  - Lipid signalling molecules are essential components of the processes that allow
      one extracellular signal to be transferred inside the nucleus, where specific
      lipid second messengers elicit reactions capable of regulating gene
      transcription, DNA replication or repair and DNA cleavage, eventually resulting
      in cell growth, differentiation, apoptosis or many other cell functions. Nuclear
      inositides are independently regulated, suggesting that the nucleus constitutes a
      functionally distinct compartment of inositol lipids metabolism. Indeed, nuclear
      inositol lipids themselves can modulate nuclear processes, such as transcription
      and pre-mRNA splicing, growth, proliferation, cell cycle regulation and
      differentiation. Nuclear PI-PLCbeta1 is a key molecule for nuclear inositide
      signalling, where it plays a role in cell cycle progression, proliferation and
      differentiation. Here we review the targets and possible involvement of nuclear
      PI-PLCbeta1 in human physiology and pathology. 

PMID- 24296033
TI  - The Saccharomyces cerevisiae gene YPR011c encodes a mitochondrial transporter of
      adenosine 5'-phosphosulfate and 3'-phospho-adenosine 5'-phosphosulfate.
AB  - The genome of Saccharomyces cerevisiae contains 35 members of the mitochondrial
      carrier family, nearly all of which have been functionally characterized. In this
      study, the identification of the mitochondrial carrier for adenosine 5'
      phosphosulfate (APS) is described. The corresponding gene (YPR011c) was
      overexpressed in bacteria. The purified protein was reconstituted into
      phospholipid vesicles and its transport properties and kinetic parameters were
      characterized. It transported APS, 3'-phospho-adenosine 5'-phosphosulfate,
      sulfate and phosphate almost exclusively by a counter-exchange mechanism.
      Transport was saturable and inhibited by bongkrekic acid and other inhibitors. To
      investigate the physiological significance of this carrier in S. cerevisiae,
      mutants were subjected to thermal shock at 45 degrees C in the presence of
      sulfate and in the absence of methionine. At 45 degrees C cells lacking YPR011c,
      engineered cells (in which APS is produced only in mitochondria) and more so the
      latter cells, in which the exit of mitochondrial APS is prevented by the absence
      of YPR011cp, were less thermotolerant. Moreover, at the same temperature all
      these cells contained less methionine and total glutathione than wild-type cells.
      Our results show that S. cerevisiae mitochondria are equipped with a transporter
      for APS and that YPR011cp-mediated mitochondrial transport of APS occurs in S.
      cerevisiae under thermal stress conditions. 

PMID- 24296034
TI  - Dark-adapted spinach thylakoid protein heterogeneity offers insights into the
      photosystem II repair cycle.
AB  - In higher plants, thylakoid membrane protein complexes show lateral heterogeneity
      in their distribution: photosystem (PS) II complexes are mostly located in grana
      stacks, whereas PSI and adenosine triphosphate (ATP) synthase are mostly found in
      the stroma-exposed thylakoids. However, recent research has revealed strong
      dynamics in distribution of photosystems and their light harvesting antenna along
      the thylakoid membrane. Here, the dark-adapted spinach (Spinacia oleracea L.)
      thylakoid network was mechanically fragmented and the composition of distinct
      PSII-related proteins in various thylakoid subdomains was analyzed in order to
      get more insights into the composition and localization of various PSII
      subcomplexes and auxiliary proteins during the PSII repair cycle. Most of the
      PSII subunits followed rather equal distribution with roughly 70% of the proteins
      located collectively in the grana thylakoids and grana margins; however, the low
      molecular mass subunits PsbW and PsbX as well as the PsbS proteins were found to
      be more exclusively located in grana thylakoids. The auxiliary proteins assisting
      in repair cycle of PSII were mostly located in stroma-exposed thylakoids, with
      the exception of THYLAKOID LUMEN PROTEIN OF 18.3 (TLP18.3), which was more evenly
      distributed between the grana and stroma thylakoids. The TL29 protein was present
      exclusively in grana thylakoids. Intriguingly, PROTON GRADIENT REGULATION5 (PGR5)
      was found to be distributed quite evenly between grana and stroma thylakoids,
      whereas PGR5-LIKE PHOTOSYNTHETIC PHENOTYPE1 (PGRL1) was highly enriched in the
      stroma thylakoids and practically missing from the grana cores. This article is
      part of a special issue entitled: photosynthesis research for sustainability:
      keys to produce clean energy.

PMID- 24296035
TI  - Improved safety with intravenous insulin therapy for critically ill patients with
      renal failure.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a new
      intravenous (IV) regular human insulin infusion (RHI) algorithm for glycemic
      control in critically ill patients with renal failure. METHODS: Adult trauma
      patients with renal failure who received a new RHI algorithm were compared with
      those who received the discontinued RHI algorithm (historical control). Target
      blood glucose (BG) concentration was 70 to 149 mg/dL (3.9-8.3 mmol/L). Patients
      were evaluated for 7 d while receiving the RHI infusion and continuous enteral or
      parenteral nutrition. RESULTS: Mean BG was higher for the new RHI algorithm group
      (n = 25) compared with control (n = 21): 145 +/- 10 mg/dL or 8.1 +/- 0.6 mmol/L
      versus 133 +/- 14 mg/dL or 7.4 +/- 0.8 mmol/L (P = 0.001). The new RHI algorithm
      resulted in less time within the target BG range (11.9 +/- 2.5 h/d versus 16.1 +/
      3.3 h/d; P = 0.001); however, BGs were within 70 to 179 mg/dL (or 3.9-10 mmol/L)
      for 16.3 +/- 2.6 h/d. The proportion of patients who experienced an episode of
      moderate hypoglycemia (BG 40-60 mg/dL or 2.2-3.3 mmol/L) or severe hypoglycemia
      (BG < 40 mg/dL or 2.2 mmol/L) was decreased (32% versus 76%; P = 0.001) and
      eliminated (0% versus 29%, P = 0.006), respectively. CONCLUSIONS: The new RHI
      algorithm improved patient safety by decreasing the prevalence of moderate
      hypoglycemia and eliminating severe hypoglycemia. The duration of glycemic
      control within the target BG range was decreased, but acceptable within a higher
      target BG ceiling.

PMID- 24296036
TI  - Effect of yellow capsicum extract on proliferation and differentiation of 3T3-L1
      preadipocytes.
AB  - OBJECTIVES: To evaluate the effect of effect of Yellow Capsicum extract (YCE)
      that is rich in capsaicin on the proliferation and differentiation of 3T3-L1
      preadipocytes in vitro. METHODS: 3T3 L1 cells that were exposed to
      differentiation-inducing medium containing high glucose DMEM (Dulbecco's Modified
      Eagle's Medium) and subsequently were treated with capsaicin and YCE for their
      effect on adipocyte differentiation, changes in their triglyceride content,
      leptin secretion, expression of lipoprotein lipase, PPARgamma, and CCAAT/enhancer
      binding protein alpha (C/EBPalpha). RESULTS: Both YCE and capsaicin inhibited
      proliferation and differentiation 3T3-L1 preadipocytes and suppressed
      accumulation of intracellular triglyceride in a dose-dependent manner. In
      addition, a significant decrease in the expression of lipoprotein lipase (LPL),
      leptin, PPARgamma, and C/EBPalpha was noted in 3T3-L1 preadipocytes when induced
      to differentiate by YCE and Capsaicin. CONCLUSIONS: The potent inhibitory action
      of YCE and Capsaicin on the differentiation of 3T3-L1 preadipocyte observed
      suggests that they (YCE and Capsaicin) have the potential to inhibit obesity that
      needs to be explored in future studies.

PMID- 24296037
TI  - Characterization of 114 insertion/deletion (INDEL) polymorphisms, and selection
      for a global INDEL panel for human identification.
AB  - Bi-Allelic Insertions and Deletions (INDELs) are a powerful set of genetic
      markers for Human Identification (HID). They have certain desirable features,
      such as low mutation rates, no stutter, and potentially small amplicon sizes that
      could prove effective in some circumstances. In this study, we analyzed the
      distribution of 114 INDELs in four North American populations (Caucasian, African
      American, Southwest Hispanic, and Asian) to estimate their distribution in major
      global populations. Of the 114 INDELs a primary panel of 38 candidate markers was
      selected that met the criteria of (1) a minimum allele frequency of greater than
      0.20 across the populations studied; (2) general concordance with Hardy-Weinberg
      equilibrium (HWE) expectations; (3) relatively low FST based on the major
      populations; (4) physical distance between markers greater than 40 Mbp; and (5) a
      lack of linkage disequilibria between syntenic markers. Additionally, another 11
      supplemental markers were selected for an expanded panel of 49 markers which met
      the above criteria, with the exception that they are separated at least by 20
      Mbp. The resulting panels had Random Match Probabilities that were at least 10(
      16) and 10(-19), respectively, and combined FST values of approximately 0.02.
      Given these findings, these INDELs should be useful for HID.

PMID- 24296038
TI  - Evaluation of a co-extraction method for real-time PCR-based body fluid
      identification and DNA typing.
AB  - Body fluid identification and individual identification are an important series
      of tests in usual criminal investigations. Recent reports have demonstrated a new
      approach using DNA/RNA co-extraction methods in which RNA for body fluid
      identification and DNA for short tandem repeat (STR) typing are extracted
      simultaneously from the same sample. This study evaluated a standard co
      extraction kit, the AllPrep(r) DNA/RNA Mini Kit, in order to demonstrate the
      availability of the co-extraction procedure for those real-time polymerase chain
      reaction-based body fluid identification methods that we have validated
      previously. We demonstrated that the use of the Allprep Kit, for which we
      adjusted the lysis temperature to 56 degrees C to improve extraction efficiency,
      can simultaneously extract sufficient RNA and DNA for body fluid identification
      and STR analysis; however, a longer incubation at a high temperature slightly
      affected the DeltaCt value of each target gene and appeared to be not as
      effective for DNA extraction from old stains as from 1-day-old stains. This
      method is promising for future forensic investigations because the use of this
      kit can reduce sample consumption for body fluid identification and DNA typing. 

PMID- 24296039
TI  - In situ TEM study of stability of TaRhx diffusion barriers using a novel sample
      preparation method.
AB  - The atomic diffusion mechanisms associated with metallurgical failure of TaRhx
      diffusion barriers for Cu metallizations were studied by in situ transmission
      electron microscopy (TEM). The issues related to in situ heating of focused ion
      beam (FIB) prepared cross-sectional TEM samples that contain Cu thin films are
      discussed. The Cu layer in Si/(13 nm)TaRhx/Cu stacks showed grain growth and
      formation of voids at temperatures exceeding 550 degrees C. For Si/(43
      nm)TaRhx/Cu stacks, grain growth of Cu was delayed to higher temperatures, i.e.,
      700 degrees C, and void formation was not observed. Extensive surface diffusion
      of Cu, however, preceded bulk diffusion. Therefore, a 10 nm film of electron beam
      evaporated C was deposited on both sides of the TEM lamellae to limit surface
      diffusion. This processing technique allowed for direct observation of atomic
      diffusion and reaction mechanisms across the TaRhx interface. Failure occurred by
      nucleation of orthorhombic RhSi particles at the Si/TaRhx interface.
      Subsequently, the barrier at areas adjacent to RhSi particles was depleted in Rh.
      This created lower density areas in the barrier, which facilitated diffusion of
      Cu to the Si substrate to form Cu3Si. The morphology of an in situ annealed
      lamella was compared with an ex situ bulk annealed sample, which showed similar
      reaction morphology. The sample preparation method developed in this study
      successfully prevented surface diffusion/delamination of the Cu layer and can be
      employed to understand the metallurgical failure of other potential diffusion
      barriers.

PMID- 24296040
TI  - Cybernetic modeling of adaptive prediction of environmental changes by
      microorganisms.
AB  - Microorganisms exhibit varied regulatory strategies such as direct regulation,
      symmetric anticipatory regulation, asymmetric anticipatory regulation, etc.
      Current mathematical modeling frameworks for the growth of microorganisms either
      do not incorporate regulation or assume that the microorganisms utilize the
      direct regulation strategy. In the present study, we extend the cybernetic
      modeling framework to account for asymmetric anticipatory regulation strategy.
      The extended model accurately captures various experimental observations. We use
      the developed model to explore the fitness advantage provided by the asymmetric
      anticipatory regulation strategy and observe that the optimal extent of
      asymmetric regulation depends on the selective pressure that the microorganisms
      experience. We also explore the importance of timing the response in anticipatory
      regulation and find that there is an optimal time, dependent on the extent of
      asymmetric regulation, at which microorganisms should respond anticipatorily to
      maximize their fitness. We then discuss the advantages offered by the cybernetic
      modeling framework over other modeling frameworks in modeling the asymmetric
      anticipatory regulation strategy. 

PMID- 24296041
TI  - Canalization: what the flux?
AB  - Polarized transport of the hormone auxin plays crucial roles in many processes in
      plant development. A self-organizing pattern of auxin transport--canalization--is
      thought to be responsible for vascular patterning and shoot branching regulation
      in flowering plants. Mathematical modeling has demonstrated that membrane
      localization of PIN-FORMED (PIN)-family auxin efflux carriers in proportion to
      net auxin flux can plausibly explain canalization and possibly other auxin
      transport phenomena. Other plausible models have also been proposed, and there
      has recently been much interest in producing a unified model of all auxin
      transport phenomena. However, it is our opinion that lacunae in our understanding
      of auxin transport biology are now limiting progress in developing the next
      generation of models. Here we examine several key areas where significant
      experimental advances are necessary to address both biological and theoretical
      aspects of auxin transport, including the possibility of a unified transport
      model.

PMID- 24296042
TI  - Increased TRH and TRH-like peptide release in rat brain and peripheral tissues
      during proestrus/estrus.
AB  - Women are at greater risk for major depression, PTSD, and other anxiety
      disorders. ERbeta-selective agonists for the treatment of these disorders are the
      focus of pharmacologic development and clinical testing. Estradiol and its
      metabolites contribute to the neuroprotective effects of this steroid class,
      particularly in men, due to local conversion of testosterone to estiradiol in key
      brain regions which are predisposed to neurodegenerative diseases. We have used
      young adult female Sprague-Dawley rats to assess the role of TRH and TRH-like
      peptides, with the general structure pGlu-X-Pro-NH2 where "X" can be any amino
      acid residue, as mediators of the neurobiochemical effects of estradiol. The
      neuroprotective TRH and TRH-like peptides are coreleased with excitotoxic
      glutamate by glutamatergic neurons which contribute importantly to the regulation
      of the estrus cycle. The levels of TRH and TRH-like peptides during proestrus
      and/or estrus in the 12 brain regions analyzed were significantly decreased (due
      to accelerated release) 106 times but increased only 25 times when compared to
      the corresponding levels during diestrus days 1 and 2. These changes, listed by
      brain region in the order of decreasing number of significant decreases (?)
      and/or increases (?), were: striatum (20?,1?), medulla oblongata (16?,2?),
      amygdala (14?,1?), cerebellum (13?,1?), hypothalamus (12?,1?), entorhinal cortex
      (6?,6?), posterior cingulate (10?,1?), frontal cortex (3?,5?), nucleus accumbens
      (5?,3?), hippocampus (5?,2?), anterior cingulate (2?,1?), and piriform cortex
      (1?). In peripheral tissues the corresponding changes were: ovaries (23?), uterus
      (16?,1?), adrenals (11?,3?), and pancreas (1?,6?). We conclude that these
      peptides may be downstream mediators of some of the therapeutic effects of
      estrogen. 

PMID- 24296043
TI  - Relationship between neutrophil influx and oxidative stress in alveolar space in
      lipopolysaccharide-induced lung injury.
AB  - We intratracheally administered lipopolysaccharide (LPS) to ICR mice and then
      collected BAL fluid and lung tissue to determine whether levels of neutrophils
      and/or myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid reflect lung
      tissue damage. Robust neutrophil accumulation into the alveolar space and lung
      tissue were almost completely abolished at seven days along with oxidative stress
      markers in the lung. However, lung injury scores and lung wet/dry ratios, as well
      as MPO and oxidative stress markers in BAL fluid were significantly increased at
      five and seven days after LPS administration. At later time points, BAL
      neutrophils generated more MPO activity and ROS than those harvested sooner after
      LPS administration. Although elevated neutrophil levels in BAL fluid reflected
      oxidative stress in the lungs, MPO might serve as a useful marker to evaluate
      damage sustained by epithelial cells over the long term. 

PMID- 24296044
TI  - Aspects of nonviral gene therapy: correlation of molecular parameters with
      lipoplex structure and transfection efficacy in pyridinium-based cationic lipids.
AB  - This study seeks correlations between the molecular structures of cationic and
      neutral lipids, the lipid phase behavior of the mixed-lipid lipoplexes they form
      with plasmid DNA, and the transfection efficacy of the lipoplexes. Synthetic
      cationic pyridinium lipids were co-formulated (1:1) with the cationic lipid 1,2
      dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and these lipids were co
      formulated (3:2) with the neutral lipids 1,2-dioleoyl-sn-glycero-3
      phosphatidylethanolamine (DOPE) or cholesterol. All lipoplex formulations
      exhibited plasmid DNA binding and a level of protection from DNase I degradation.
      Composition-dependent transfection (beta-galactosidase and GFP) and cytotoxicity
      was observed in Chinese hamster ovarian-K1 cells. The most active formulations
      containing the pyridinium lipids were less cytotoxic but of comparable activity
      to a Lipofectamine 2000TM control. Molecular structure parameters and partition
      coefficients were calculated for all lipids using fragment additive methods. The
      derived shape parameter values correctly correlated with observed hexagonal lipid
      phase behavior of lipoplexes as derived from small-angle X-ray scattering
      experiments. A transfection index applicable to hexagonal phase lipoplexes
      derived from calculated parameters of the lipid mixture (partition coefficient,
      shape parameter, lipoplex packing) produced a direct correlation with
      transfection efficiency. 

PMID- 24296045
TI  - The effect of simvastatin-loaded polymeric microspheres in a critical size bone
      defect in the rabbit calvaria.
AB  - The present study describes the development of a microsphere capsule based on
      polylactide-co-glycolide (PLGA) loaded with simvastatin that was subsequently
      incorporated into synthetic bone cement. The osteogenic effect of simvastatin
      loaded bone cement was in a critical sized defect in vivo to test the hypothesis
      the biologic response would be different depending on the dosage of simvastatin
      applied to bone cement. Our results showed that simvastatin loaded PLGA
      microspheres can be successfully obtained through O/W emulsion/solvent
      evaporation method with appropriate morphologic characteristics and high
      encapsulation efficiency for incorporation in bone cements. The biodegradable
      characteristic of the microspheres successfully presented a slow release and the
      duration of the release lasted for more than 1 month. The in vivo experiment
      revealed that the microspheres containing simvastatin significantly enhanced bone
      formation in the rabbit calvaria critical size defect. 

PMID- 24296046
TI  - Asymmetric flow field-flow fractionation (AF4) for the quantification of
      nanoparticle release from tablets during dissolution testing.
AB  - Nanoparticles composed of poly(DL-lactide-co-glycolide) (PLGA) represent
      promising colloidal drug carriers for improved drug targeting. Although most
      research activities are focused on intravenous application of these carriers the
      peroral administration is described to improve bioavailability of poorly soluble
      drugs. Based on these insights the manuscript describes a model tablet
      formulation for PLGA-nanoparticles and especially its analytical characterisation
      with regard to a nanosized drug carrier. Besides physico-chemical tablet
      characterisation according to pharmacopoeias the main goal of the study was the
      development of a suitable analytical method for the quantification of
      nanoparticle release from tablets. An analytical flow field-flow fractionation
      (AF4) method was established and validated which enables determination of
      nanoparticle content in solid dosage forms as well as quantification of particle
      release during dissolution testing. For particle detection a multi-angle light
      scattering (MALS) detector was coupled to the AF4-system. After dissolution
      testing, the presence of unaltered PLGA-nanoparticles was successfully proved by
      dynamic light scattering and scanning electron microscopy. 

PMID- 24296047
TI  - Enhanced cellular uptake by "pharmaceutically oriented devices" of new simplified
      analogs of Linezolid with antimicrobial activity.
AB  - The aim of the present study was to enhance cellular uptake of simplified analogs
      of Linezolid by their incorporation into suitable delivery devices in order to
      improve the antimicrobial activity of these novel synthesized oxazolidin-2-one
      derivatives. The oxazolidin-2-one derivatives were synthesized by developing a
      rather simple one-pot reaction starting from oxiranylmethanol and several primary
      amines. Three delivery devices were prepared by following different synthetic
      approaches, such as single-step free radical grafting, precipitation
      polymerization and nano-emulsion. Finally, the antimicrobial activity of the
      novel synthesized compounds, without any vehicle and after their incorporation
      into the delivery devices, was evaluated against Escherichia coli and
      Saccharomyces cerevisiae by performing time-kill analyses. The synthesized
      oxazolidinones exhibited modest antimicrobial activity against E. coli and S.
      cerevisiae (MIC 16 MUg/mL). A good activity was, instead, highlighted after their
      incorporation into the prepared delivery devices (lecithin-based nano-emulsion,
      poly(N-vinyl-pyrrolidone)-methacrylic acid grafted copolymer and spherical
      polymeric nanoparticles) (MIC<=4 MUg/mL). The incorporation into suitable
      vehicles, indeed, reduced by 4 times the normal MICs of the newly synthesized
      oxazolilidin-2-ones and represents an effective strategy to overcome cellular
      penetration constraints.

PMID- 24296048
TI  - Deposition and fine particle production during dynamic flow in a dry powder
      inhaler: a CFD approach.
AB  - In this work the dynamic flow as well as the particle motion and deposition in a
      commercial dry powder inhaler, DPI (i.e., Turbuhaler) is described using
      computational fluid dynamics, CFD. The dynamic flow model presented here is an
      extension of a steady flow model previously described in Milenkovic et al.
      (2013). The model integrates CFD simulations for dynamic flow, an Eulerian
      fluid/Lagrangian-particle description of particle motion as well as a
      particle/wall interaction model providing the sticking efficiency of particles
      colliding with the DPI walls. The dynamic flow is imposed by a time varying
      outlet pressure and the particle injections into the DPI are assumed to occur
      instantaneously and follow a prescribed particle size distribution, PSD. The
      total particle deposition and the production of fine particles in the DPI are
      determined for different peak inspiratory flow rates, PIFR, flow increase rates,
      FIR, and particle injection times. The simulation results for particle deposition
      are found to agree well with available experimental data for different values of
      PIFR and FIR. The predicted values of fine particle fraction are in agreement
      with available experimental results when the mean size of the injected PSD is
      taken to depend on the PIFR. 

PMID- 24296049
TI  - Differentiating transpiration from evaporation in seasonal agricultural wetlands
      and the link to advective fluxes in the root zone.
AB  - The current state of science and engineering related to analyzing wetlands
      overlooks the importance of transpiration and risks data misinterpretation. In
      response, we developed hydrologic and mass budgets for agricultural wetlands
      using electrical conductivity (EC) as a natural conservative tracer. We developed
      simple differential equations that quantify evaporation and transpiration rates
      using flow rates and tracer concentrations at wetland inflows and outflows. We
      used two ideal reactor model solutions, a continuous flow stirred tank reactor
      (CFSTR) and a plug flow reactor (PFR), to bracket real non-ideal systems. From
      those models, estimated transpiration ranged from 55% (CFSTR) to 74% (PFR) of
      total evapotranspiration (ET) rates, consistent with published values using
      standard methods and direct measurements. The PFR model more appropriately
      represents these non-ideal agricultural wetlands in which check ponds are in
      series. Using a flux model, we also developed an equation delineating the root
      zone depth at which diffusive dominated fluxes transition to advective dominated
      fluxes. This relationship is similar to the Peclet number that identifies the
      dominance of advective or diffusive fluxes in surface and groundwater transport.
      Using diffusion coefficients for inorganic mercury (Hg) and methylmercury (MeHg)
      we calculated that during high ET periods typical of summer, advective fluxes
      dominate root zone transport except in the top millimeters below the sediment
      water interface. The transition depth has diel and seasonal trends, tracking
      those of ET. Neglecting this pathway has profound implications: misallocating
      loads along different hydrologic pathways; misinterpreting seasonal and diel
      water quality trends; confounding Fick's First Law calculations when determining
      diffusion fluxes using pore water concentration data; and misinterpreting
      biogeochemical mechanisms affecting dissolved constituent cycling in the root
      zone. In addition, our understanding of internal root zone cycling of Hg and
      other dissolved constituents, benthic fluxes, and biological irrigation may be
      greatly affected. 

PMID- 24296050
TI  - Climatic variation and runoff from partially-glacierised Himalayan tributary
      basins of the Ganges.
AB  - Climate records for locations across the southern slope of the Himalaya between
      77 degrees E and 91 degrees E were selected together with discharge measurements
      from gauging stations on rivers draining partially-glacierised basins tributary
      to the Ganges, with a view to assessing impacts of climatic fluctuations on year
      to-year variations of runoff during a sustained period of glacier decline. The
      aims were to describe temporal patterns of variation of glaciologically- and
      hydrologically-relevant climatic variables and of river flows from basins with
      differing percentages of ice-cover. Monthly precipitation and air temperature
      records, starting in the mid-nineteenth century at high elevation sites and
      minimising data gaps, were selected from stations in the Global Historical
      Climatology Network and CRUTEM3. Discharge data availability was limited to post
      1960 for stations in Nepal and at Khab in the adjacent Sutlej basin. Strengths of
      climate-runoff relationships were assessed by correlation between overlapping
      portions of annual data records. Summer monsoon precipitation dominates runoff
      across the central Himalaya. Flow in tributaries of the Ganges in Nepal
      fluctuated from year to year but the general background level of flow was usually
      maintained from the 1960s to 2000s. Flow in the Sutlej, however, declined by 32%
      between the 1970s and 1990s, reflecting substantially reduced summer
      precipitation. Over the north-west Ganges-upper Sutlej area, monsoon
      precipitation declined by 30-40% from the 1960s to 2000s. Mean May-September air
      temperatures along the southern slope of the central Himalayas dipped from the
      1960s, after a long period of slow warming or sustained temperatures, before
      rising rapidly from the mid-1970s so that in the 2000s summer air temperatures
      reached those achieved in earlier warmer periods. There are few measurements of
      runoff from highly-glacierised Himalayan headwater basins; runoff from one of
      which, Langtang Khola, was less than that of the monsoon-dominated Narayani
      river, in which basin Langtang is nested. 

PMID- 24296052
TI  - Water extract of Pueraria lobata Ohwi has anti-viral activity against human
      respiratory syncytial virus in human respiratory tract cell lines.
AB  - Human respiratory syncytial virus (HRSV) infects all age groups and causes
      bronchiolitis, pneumonia, and acute respiratory distress syndrome with a
      significant mortality rate. To date, only ribavirin has been used to manage HRSV
      infection. However, ribavirin is expensive with an only modest effect.
      Furthermore, ribavirin has several side effects, which means it has limited
      clinical benefit. Pueraria lobata Ohwi (P. lobata) is a common ingredient of Ge
      Gen-Tang (Kakkon-to) and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to), which are
      prescriptions of Chinese traditional medicine proven to have antiviral activity
      against HRSV. Therefore, it was hypothesized that P. lobata might be effective
      against HRSV. To find a cost-effective therapeutic modality, both human upper
      (HEp-2) and lower (A549) respiratory tract cell lines were used to test the
      hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results
      showed that the water extract of P. lobata was effective (p < 0.0001) against
      HRSV-induced plaque formation. P. lobata was more effective when given prior to
      viral inoculation (p < 0.0001) by inhibiting viral attachment (p < 0.0001) and
      penetration (p < 0.0001). However, supplementation with P. lobata could not
      stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has
      antiviral activity against HRSV-induced plaque formation in airway mucosa mainly
      by inhibiting viral attachment and internalization. Further identification of
      effective constituents could contribute to the prevention of HRSV infection. 

PMID- 24296051
TI  - Prostaglandin E2 modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 cells
      in a PKA-dependent manner.
AB  - The effect of prostaglandin E2 (PGE2) on bone mass has been well-established in
      vivo. Previous studies have showed that PGE2 increases differentiation,
      proliferation, and regulates cell morphology through F-actin stress fiber in
      statically cultured osteoblasts. However, the effect of PGE2 on osteoblasts in
      the presence of fluid shear stress (FSS), which could better uncover the anabolic
      effect of PGE2 in vivo, has yet to be examined. Here, we hypothesized that PGE2
      modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 osteoblastic cells
      through protein kinase A (PKA) pathway. Furthermore, this PGE2-induced F-actin
      remodeling was associated with the recovery of cellular mechanosensitivity. Our
      data showed that treatment with 10 nM dmPGE2 for 15 min significantly suppressed
      the F-actin stress fiber intensity in FSS-stimulated cells in a PKA-dependent
      manner. In addition, dmPGE2 treatment enhanced the cells' calcium peak magnitude
      and the percentage of responding cells in the second FSS stimulation, though
      these effects were abolished and attenuated by co-treatment with phalloidin. Our
      results demonstrated that 10 nM dmPGE2 was able to accelerate the 'reset' process
      of F-actin stress fiber to its pre-stimulated level partially through PKA
      pathway, and thus promoted the recovery of cellular mechanosensitivity. Our
      finding provided a novel cellular mechanism by which PGE2 increased bone
      formation as shown in vivo, suggesting that PGE2 could be a potential target for
      treatments of bone formation-related diseases. 

PMID- 24296053
TI  - Bacterial colonization of double J stents and bacteriuria frequency.
AB  - Stents and catheters are widely used in urology. In this study, the frequency of
      double J (DJ) stent colonization and stent-associated bacteriuria was
      investigated. Between June 2011 and June 2012, 130 patients (17-72 years old) who
      underwent DJ stenting were enrolled in the study. Surgeries prior to stenting
      included stone extraction/lithotripsy, endopyelotomy, and diagnostic
      ureteroscopy. Prior to stenting, sterile urine samples were obtained, and urinary
      cultures were performed upon removal of the DJ stents, the second procedure. DJ
      stent cultures were also performed. Sixty-three stents were inserted into the
      right ureter and 67 into the left ureter of the patients. Cultures showed
      bacterial colonization in 10 (7.7%) cases. There was no significant association
      between positive stent culture and patient age, sex, or stent laterality. The
      rate of colonization was 2.2%, 2.9%, and 25% when indwelling time was less than 4
      weeks, 4-6 weeks, and more than 6 weeks, respectively. In the present study, the
      rate of infection associated with a DJ stent and urinary infection was not very
      high. However, bacterial colonization increases significantly with indwelling
      time of the stent, and sterile culture of urine does not rule out colonization of
      the stent. Bacteriological investigation showed very low rates of colonization
      within 6 weeks after the insertion of stents, indicating that ureteral stents can
      be used safely within that time period.

PMID- 24296054
TI  - Preoperative elevation of serum C-reactive protein as an indicator of poor
      prognosis for early-stage esophageal squamous cell carcinoma.
AB  - Preoperative elevation of serum C-reactive protein (CRP) is reportedly associated
      with poor prognosis in several types of cancer. This study investigated the role
      of serum CRP as a prognostic factor in early-stage esophageal squamous cell
      carcinoma (ESCC). The preoperative serum CRP levels were measured in 156 newly
      diagnosed pT1-2N0M0 patients using an enzyme-linked immunosorbent assay.
      Correlations between serum CRP levels and other clinical parameters were
      analyzed. Multivariate analyses were performed to find prognostic markers using
      Cox's proportional hazards model. CRP concentrations were within the normal range
      in 117 (75%) individuals, but were elevated in 39 (25%) patients. Serum CRP
      levels were significantly correlated with the tumor length (p = 0.032), depth (T
      classification, p = 0.0157), or histologic grade (p = 0.034). The overall 5-year
      survival rates were 76.3% and 50.2% in the low- and high-CRP groups, respectively
      (p = 0.005). By multivariate analyses, the elevated serum CRP level was found to
      be an independent prognostic factor for poor survival (hazard ratio = 2.131; p =
      0.007), regardless of tumor classification or other prognostic factors. In
      conclusion, preoperative, high serum CRP is an independent determinant of poor
      prognosis in early-stage ESCC.

PMID- 24296055
TI  - Predictive value of vertebral artery extracranial color-coded duplex sonography
      for ischemic stroke-related vertigo.
AB  - Vertigo can be a major presentation of posterior circulation stroke and can be
      easily misdiagnosed because of its complicated presentation. We thus
      prospectively assessed the predictive value of vertebral artery extracranial
      color-coded duplex sonography (ECCS) for the prediction of ischemic stroke
      related vertigo. The inclusion criteria were: (1) a sensation of whirling
      (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate
      treatment; and (3) those who could complete cranial magnetic resonance imaging
      (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive
      participants with vertigo were enrolled from Kaohsiung Municipal Hsiao-Kang
      Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic
      data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed.
      We chose the parameters of peak systolic velocity (PSV), end diastolic velocity
      (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index
      (PI) to represent the hemodynamics. Values from both sides of V2 segments were
      averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV
      (aPSV)/EDV, and average (aMV). Axial and coronal diffusion-weighted MRI findings
      determined the existence of acute ischemic stroke. We grouped and analyzed
      participants in two ways (way I and way II analyses) based on the diffusion
      weighted MRI findings (to determine whether there was acute stroke) and
      neurological examinations. Using way I analysis, the "MRI (+)" group had
      significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity
      (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the "MRI (-)" group. The cutoff
      value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between
      the MRI (+) and MRI (-) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0
      (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066),
      0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0.0068), respectively. Using
      way II analysis, lower aEDV and aMV, and higher aRI, aPI, and aPSV/EDV ratio
      could determine the "MRI (+) without focal signs" group. The cutoff
      value/sensitivity/specificity of aEDV, aMV, aPI, aRI, and aPSV/EDV between the
      MRI (+) without focal signs and MRI (-) groups were 9.10/71.4/96.0 (p = 0.0005),
      15.65/57.1/96.0 (p = 0.0124), 1.10/100/70.0 (p = 0.0002), 0.64/100/70.0 (p =
      0.0023), and 2.80/100/70.0 (p = 0.0017), respectively. In conclusion, using
      demographic data and clinical symptoms, it was difficult to determine the
      patients with ischemic stroke-related vertigo. Although neurological examinations
      still have diagnostic value, the high impedance and low velocity pattern of V2
      ECCS can be an add-on method for the screening of acute ischemic stroke-related
      vertigo, even for those without focal neurological signs.

PMID- 24296056
TI  - Prevalence, correlates, and risk perception of HIV infection among heroin users
      in Central Taiwan.
AB  - We investigated the prevalence and correlated factors of human immunodeficiency
      virus (HIV) among heroin users attending methadone maintenance treatment (MMT)
      programs in Central Taiwan, and explored the degree of risk perception of HIV
      infection among the participants. Our study participants were 781 heroin users
      seeking treatment at the MMT program at Tsaotun Psychiatric Center in Taiwan. The
      presence of HIV antibodies was identified by microparticle enzyme immunoassay and
      confirmed by western blot. Multivariate logistic regression was used to identify
      the independent correlates of HIV infection. The mean age of the sample was 36.1
      years [standard deviation (SD) = 7.6]; of the patients, 710 (90.9%) were men. The
      prevalence of HIV infection among our study population was 20.7%. Multivariate
      logistic regression analysis revealed that HIV infection was independently
      associated with the age of the patients of initial heroin use, heroin injection
      use, nondrug-related criminal convictions, needle-sharing behaviors, and sharing
      injection paraphernalia. A strong agreement existed between self-reported HIV
      serostatus and the results of laboratory analyses, with 88.8% of patients
      reporting their condition correctly. We found a high rate of HIV infection among
      patients in the MMT program. Factors associated with HIV infection were mostly
      related to drug-use behaviors. These findings stress the importance of education
      regarding drug-risk behaviors.

PMID- 24296057
TI  - The role of cognitive event-related potentials in executive dysfunction.
AB  - Frontal lobes are great and are a late-developing region of the neocortex that
      play a critical role in human behavior and executive function. The aim of this
      study was to clarify the role of event-related potentials (ERPs) in executive
      dysfunction and its relationship between generator mechanism and cognitive
      significance. We recruited 20 patients with frontal lobe lesion (FLL) and 27 age
      matched controls. All patients submitted to comprehensive Frontal Test Battery
      and auditory ERPs measurement. In comparison with controls, the patients with FLL
      had significantly decreased executive function and manifested the delay of P300
      latency, which reflected a delay of mental processing speed in these patients.
      Our findings suggest that patients with FLL may have prolonged P300 latency,
      which has a good correlation with executive dysfunction, poor performance, and
      longer P300 latencies. P300 ERPs are considered to be a useful method to identify
      the alteration of frontal-parietal connection.

PMID- 24296058
TI  - A case of acromegaly complicated with diabetic ketoacidosis, pituitary apoplexy,
      and lymphoma.
AB  - Acromegaly is always complicated with comorbidities and increased mortality. The
      disease activity and mortality outcomes are highly correlated to the level of
      growth hormone and insulin-like growth factor 1. A variety of clinical
      manifestations of acromegaly have been reported. We present a unique case where a
      49-year-old male was diagnosed with acromegaly with a first manifestation as an
      episode of diabetic ketoacidosis. Because he refused any suggestion of treatment,
      a recurrent episode of diabetic ketoacidosis with pituitary apoplexy occurred. A
      huge B-cell lymphoma displaying as a huge facial mass followed within 1 year of
      the diagnosis of acromegaly. Death from advanced cancer ensued 3 years later.
      This clinical experience strongly reinforces the urgency of controlling growth
      hormone and insulin-like growth factor 1 as soon as possible once acromegaly is
      diagnosed.

PMID- 24296059
TI  - Terlipressin-induced hyponatremic encephalopathy in a noncirrhotic patient.
AB  - Terlipressin, an analogue of vasopressin, is frequently used for the management
      of esophageal varices bleeding and hepatorenal syndrome. Terlipressin therapy in
      portal hypertensive patients is frequently associated with hyponatremia, but is
      rarely accompanied with serious neurological manifestations. A 39-year-old female
      with pancreatic neuroendocrine tumor, liver metastasis, main portal vein
      thrombosis, and a history of esophageal varices presented to the emergency room
      because of hematemesis. Terlipressin was given with a loading dose of 2 mg
      followed by 1 mg every 6 hours. After a total of 6 mg terlipressin injection, she
      suffered from acute delirium. Pertinent examinations showed there was no gross
      brain lesion by computed tomography, whereas her serum sodium level dropped from
      baseline (136 mmol/L) to 116 mmol/L with a serum osmolality of 256 mOsm/kg. At
      that time, urine sodium and urine osmolality were 142 mmol/L and 488 mOsm/kg,
      respectively. Under the tentative diagnosis of terlipressin-induced hyponatremic
      encephalopathy, terlipressin was withheld and hypertonic saline infusion was
      given. Within 12 hours, her serum sodium level recovered to 130 mmol/L and she
      gradually regained her cognitive functions. Although symptomatic hyponatremic
      encephalopathy is a rare complication of terlipressin treatment, close monitoring
      of serum electrolyte level is warranted in patients receiving terlipressin.

PMID- 24296060
TI  - Metronidazole-induced vertigo.

PMID- 24296061
TI  - Signal amplification for thrombin impedimetric aptasensor: sandwich protocol and
      use of gold-streptavidin nanoparticles.
AB  - In this work, we report a highly specific amplification strategy demonstrated for
      the ultrasensitive biosensing of thrombin with the use of gold-streptavidin
      nanoparticles (strep-AuNPs) and silver reduction enhancement. The biotinylated
      aptamer of thrombin was immobilized onto an avidin-graphite epoxy composite
      (AvGEC) electrode surface by affinity interaction between biotin and avidin;
      electrochemical impedance measurements were performed in a solution containing
      the redox marker ferrocyanide/ferricyanide. The change in interfacial charge
      transfer resistance (Rct) experimented by the redox marker, was recorded to
      confirm aptamer complex formation with target protein, thrombin (Thr), in a label
      free first stage. A biotinylated second thrombin aptamer, with complementary
      recognition properties was then used in a sandwich approach. The addition of
      strep-AuNPs and silver enhancement treatment led to a further increment of Rct
      thus obtaining significant signal amplification. The AptThrBio1-Thr-AptThrBio2
      sandwich formation was inspected by confocal microcopy after incubation with
      streptavidin quantum dots. In order to visualize the presence of gold
      nanoparticles, the same silver enhancement treatment was applied to electrodes
      already modified with the nanoparticle-sandwich conjugate, allowing direct
      observation by scanning electron microscopy (SEM). Results showed high
      sensitivity and selectivity for thrombin detection, with an improvement from ca.
      4.7 pM in a simple assay to 0.3 pM in the amplified reported scheme.

PMID- 24296062
TI  - A pseudo triple-enzyme cascade amplified aptasensor for thrombin detection based
      on hemin/G-quadruplex as signal label.
AB  - In this work, a pseudo triple-enzyme cascade amplified electrochemical aptasensor
      based on hemin/G-quadruplex as signal label for thrombin (TB) was constructed and
      the amplified electrochemical signal was achieved by the corporate catalysis of
      alcohol dehydrogenase-graphene sheets (ADH-GSs) bionanocomposite and hemin/G
      quadruplex, which simultaneously acted as NADH oxidase and HRP-mimicking DNAzyme.
      Through "sandwich" reaction, hemin/G-quadruplex labeled gold nanoparticles-ADH
      GSs bionanocomposite (AuNPs-ADH-GSs) was captured on electrode surface and thus
      obtained the electrochemical signal. After the addition of ethanol into the
      electrolytic cell, ADH availably catalyzed the oxidation of ethanol with the
      reduction of NAD(+) to NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed
      the oxidization of NADH, accompanying with the production of H2O2.
      Simultaneously, hemin/G-quadruplex as HRP-mimicking DNAzyme catalyzed the
      reduction of the generated H2O2. Such a catalysis strategy greatly promoted the
      electron transfer of hemin and resulted in the specific enhancement of
      electrochemical signal. The proposed TB aptasensor achieved a linear range of 1
      pM-50 nM with a detection limit of 0.3 pM (defined as S/N=3). In addition, it
      showed satisfying stability and reproducibility, good specificity and
      sensitivity, indicating promising application for the detection of various
      proteins in clinical analysis.

PMID- 24296063
TI  - 3D printed chip for electrochemical detection of influenza virus labeled with CdS
      quantum dots.
AB  - In this study, we report a new three-dimensional (3D), bead-based microfluidic
      chip developed for rapid, sensitive and specific detection of influenza
      hemagglutinin. The principle of microfluidic chip is based on implementation of
      two-step procedure that includes isolation based on paramagnetic beads and
      electrochemical detection. As a platform for isolation process, streptavidin
      modified MPs, which were conjugated via biotinylated glycan (through streptavidin
      biotin affinity) followed by linkage of hemagglutinin to glycan, were used.
      Vaccine hemagglutinin (HA vaxi) was labeled with CdS quantum dots (QDs) at first.
      Detection of the isolation product by voltammetry was the end point of the
      procedure. The suggested and developed method can be used also for detection of
      other specific substances that are important for control, diagnosis or therapy of
      infectious diseases. 

PMID- 24296064
TI  - Nosocomial infection characteristics in a burn intensive care unit: analysis of
      an eleven-year active surveillance.
AB  - AIMS: The objective of this study was to describe nosocomial infection (NI)
      rates, risk factors, etiologic agents, antibiotic susceptibility, invasive device
      utilization and invasive device associated infection rates in a burn intensive
      care unit (ICU) in Turkey. METHODS: Prospective surveillance of nosocomial
      infections was performed according to Centers for Disease Control and Prevention
      (CDC) and National Healthcare Safety Network (NHSN) criteria between 2001 and
      2012. The data was analyzed retrospectively. RESULTS: During the study period 658
      burn patients were admitted to our burn ICU. 469 cases acquired 602 NI for an
      overall NI rate of 23.1 per 1000 patient days. 109 of all the cases (16.5%) died.
      Pseudomonas aeruginosa (241), Acinetobacter baumannii (186) and Staphylococcus
      aureus (69) were the most common identified bacteria in 547 strains. CONCLUSION:
      Total burn surface area, full thickness burn, older age, presence of inhalation
      injury were determined to be the significant risk factors for acquisition of NI.
      Determining the NI profile at a certain burn ICU can lead the medical staff apply
      the appropriate treatment regimen and limit the drug resistance. Eleven years
      surveillance report presented here provides a recent data about the risk factors
      of NI in a Turkish burn ICU.

PMID- 24296065
TI  - Keeping up with video game technology: objective analysis of Xbox KinectTM and
      PlayStation 3 MoveTM for use in burn rehabilitation.
AB  - Commercially available interactive video games are commonly used in
      rehabilitation to aide in physical recovery from a variety of conditions and
      injuries, including burns. Most video games were not originally designed for
      rehabilitation purposes and although some games have shown therapeutic potential
      in burn rehabilitation, the physical demands of more recently released video
      games, such as Microsoft Xbox KinectTM (Kinect) and Sony PlayStation 3 MoveTM (PS
      Move), have not been objectively evaluated. Video game technology is constantly
      evolving and demonstrating different immersive qualities and interactive demands
      that may or may not have therapeutic potential for patients recovering from
      burns. This study analyzed the upper extremity motion demands of Kinect and PS
      Move using three-dimensional motion analysis to determine their applicability in
      burn rehabilitation. Thirty normal children played each video game while real
      time movement of their upper extremities was measured to determine maximal
      excursion and amount of elevation time. Maximal shoulder flexion, shoulder
      abduction and elbow flexion range of motion were significantly greater while
      playing Kinect than the PS Move (p<=0.01). Elevation time of the arms above 120
      degrees  was also significantly longer with Kinect (p<0.05). The physical demands
      for shoulder and elbow range of motion while playing the Kinect, and to a lesser
      extent PS Move, are comparable to functional motion needed for daily tasks such
      as eating with a utensil and hair combing. Therefore, these more recently
      released commercially available video games show therapeutic potential in burn
      rehabilitation. Objectively quantifying the physical demands of video games
      commonly used in rehabilitation aides clinicians in the integration of them into
      practice and lays the framework for further research on their efficacy. 

PMID- 24296067
TI  - Sentinel node biopsy in relation to survival in floor of the mouth carcinoma.
AB  - Promising results have been obtained with sentinel node biopsy (SNB) in early
      oral carcinoma, but the floor of the mouth remains a site at risk of
      misdiagnosis. A retrospective and prospective study was designed to test the
      safety of SNB by comparing survival among patients with early stage carcinoma of
      the floor of the mouth (FOM) undergoing SNB, to a control group managed
      traditionally by a combination of clinical observation and elective neck
      dissection (END). A total of 63 patients with early stage carcinoma of the FOM
      were treated between 1991 and 2005. In the control group, 26 patients were
      managed with END and nine by close observation. In the test group, 28 patients
      were managed prospectively with SNB. Regional recurrence occurred in 23% (8/35)
      of control patients and 25% (7/28) of test patients. Approximately 25% of
      patients were successfully treated by salvage surgery. Disease-specific survival
      was 65.5% for control patients and 85% for SNB patients; the difference was not
      statistically significant. The use of SNB in the management of cancers of the FOM
      did not adversely affect survival and prevented 69.5% of patients undergoing
      unnecessary neck dissections, while clinical progress was better in the SNB group
      than in controls. 

PMID- 24296068
TI  - Extension of the TDCR model to compute counting efficiencies for radionuclides
      with complex decay schemes.
AB  - The triple-to-double coincidence ratio (TDCR) method is frequently used to
      measure the activity of radionuclides decaying by pure beta emission or electron
      capture (EC). Some radionuclides with more complex decays have also been studied,
      but accurate calculations of decay branches which are accompanied by many
      coincident gamma transitions have not yet been investigated. This paper describes
      recent extensions of the model to make efficiency computations for more complex
      decay schemes possible. In particular, the MICELLE2 program that applies a
      stochastic approach of the free parameter model was extended. With an improved
      code, efficiencies for beta(-), beta(+) and EC branches with up to seven
      coincident gamma transitions can be calculated. Moreover, a new parametrization
      for the computation of electron stopping powers has been implemented to compute
      the ionization quenching function of 10 commercial scintillation cocktails. In
      order to demonstrate the capabilities of the TDCR method, the following
      radionuclides are discussed: (166m)Ho (complex beta(-)/gamma), (59)Fe (complex
      beta(-)/gamma), (64)Cu (beta(-), beta(+), EC and EC/gamma) and (229)Th in
      equilibrium with its progenies (decay chain with many alpha, beta and complex
      beta(-)/gamma transitions). 

PMID- 24296066
TI  - Mechanistic evaluation of the transfection barriers involved in lipid-mediated
      gene delivery: interplay between nanostructure and composition.
AB  - Here we present a quantitative mechanism-based investigation aimed at comparing
      the cell uptake, intracellular trafficking, endosomal escape and final fate of
      lipoplexes and lipid-protamine/deoxyribonucleic acid (DNA) (LPD) nanoparticles
      (NPs) in living Chinese hamster ovary (CHO) cells. As a model, two lipid
      formulations were used for comparison. The first formulation is made of the
      cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the
      zwitterionic lipid dioleoylphosphocholine (DOPC), while the second mixture is
      made of the cationic 3beta-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol
      (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine
      (DOPE). Our findings indicate that lipoplexes are efficiently taken up through
      fluid-phase macropinocytosis, while a less efficient uptake of LPD NPs occurs
      through a combination of both macropinocytosis and clathrin-dependent pathways.
      Inside the cell, both lipoplexes and LPD NPs are actively transported towards the
      cell nucleus, as quantitatively addressed by spatio-temporal image correlation
      spectroscopy (STICS). For each lipid formulation, LPD NPs escape from endosomes
      more efficiently than lipoplexes. When cells were treated with DOTAP-DOPC
      containing systems the majority of the DNA was trapped in the lysosome
      compartment, suggesting that extensive lysosomal degradation was the rate
      limiting factors in DOTAP-DOPC-mediated transfection. On the other side, escape
      from endosomes is large for DC-Chol-DOPE-containing systems most likely due to
      DOPE and cholesterol-like molecules, which are able to destabilize the endosomal
      membrane. The lipid-dependent and structure-dependent enhancement of transfection
      activity suggests that DNA is delivered to the nucleus synergistically: the
      process requires both the membrane-fusogenic activity of the nanocarrier envelope
      and the employment of lipid species with intrinsic endosomal rupture ability.

PMID- 24296069
TI  - (148g,m)Pm: evaluation of the decay schemes for two important reactor poisons.
AB  - During reactor operation (148g)Pm and (148m)Pm are formed in large quantities
      from thermal neutron capture on the fission product (147)Pm. Subsequent neutron
      capture reactions, on the (148)Pm ground state and isomer, have cross sections
      differing by a factor of 5 and so precise knowledge of their decay properties is
      vitally important. New decay scheme evaluations using the DDEP methodology for
      (148g)Pm and (148m)Pm are presented. The complete data tables and detailed
      evaluator comments are available through the DDEP website. 

PMID- 24296070
TI  - Ultrasonic cavitation of molten gallium: formation of micro- and nano-spheres.
AB  - Pure gallium has a low melting point (29.8 degrees C) and can be melted in warm
      water or organic liquids, thus forming two immiscible liquid phases. Irradiation
      of this system with ultrasonic energy causes cavitation and dispersion of the
      molten gallium as microscopic spheres. The resultant spheres were found to have
      radii range of 0.2-5 MUm and they do not coalesce upon cessation of irradiation,
      although the ambient temperature is well above the m.p. of gallium. It was found
      that the spheres formed in water are covered with crystallites of GaO(OH),
      whereas those formed in organic liquids (hexane and n-dodecane) are smooth,
      lacking such crystallites. However, Raman spectroscopy revealed that the spheres
      formed in organic liquids are coated with a carbon film. The latter may be the
      factor preventing their coalescence at temperatures above the m.p. of gallium.

PMID- 24296071
TI  - Selected reaction monitoring to determine protein abundance in Arabidopsis using
      the Arabidopsis proteotypic predictor.
AB  - In reverse genetic knockout (KO) studies that aim to assign function to specific
      genes, confirming the reduction in abundance of the encoded protein will often
      aid the link between genotype and phenotype. However, measuring specific protein
      abundance is particularly difficult in plant research, where only a limited
      number of antibodies are available. This problem is enhanced when studying gene
      families or different proteins derived from the same gene (isoforms), as many
      antibodies cross react with more than one protein. We show that utilizing
      selected reaction monitoring (SRM) mass spectrometry allows researchers to
      confirm protein abundance in mutant lines, even when discrimination between very
      similar proteins is needed. Selecting the best peptides for SRM analysis to
      ensure that protein- or gene-specific information can be obtained requires a
      series of steps, aids, and interpretation. To enable this process in Arabidopsis
      (Arabidopsis thaliana), we have built a Web-based tool, the Arabidopsis
      Proteotypic Predictor, to select candidate SRM transitions when no previous mass
      spectrometry evidence exists. We also provide an in-depth analysis of the
      theoretical Arabidopsis proteome and its use in selecting candidate SRM peptides
      to establish assays for use in determining protein abundance. To test the
      effectiveness of SRM mass spectrometry in determining protein abundance in mutant
      lines, we selected two enzymes with multiple isoforms, aconitase and malate
      dehydrogenase. Selected peptides were quantified to estimate the abundance of
      each of the two mitochondrial isoforms in wild-type, KO, double KO, and
      complemented plant lines. We show that SRM protein analysis is a sensitive and
      rapid approach to quantify protein abundance differences in Arabidopsis for
      specific and highly related enzyme isoforms. 

PMID- 24296072
TI  - Virus-based microRNA silencing in plants.
AB  - MicroRNAs (miRNAs) play pivotal roles in various biological processes across
      kingdoms. Many plant miRNAs have been experimentally identified or predicted by
      bioinformatics mining of small RNA databases. However, the functions of these
      miRNAs remain largely unknown due to the lack of effective genetic tools. Here,
      we report a virus-based microRNA silencing (VbMS) system that can be used for
      functional analysis of plant miRNAs. VbMS is performed through tobacco rattle
      virus-based expression of miRNA target mimics to silence endogenous miRNAs. VbMS
      of either miR172 or miR165/166 caused developmental defects in Nicotiana
      benthamiana. VbMS of miR319 reduced the complexity of tomato (Solanum
      lycopersicum) compound leaves. These results demonstrate that tobacco rattle
      virus-based VbMS is a powerful tool to silence endogenous miRNAs and to dissect
      their functions in different plant species. 

PMID- 24296073
TI  - Deciphering the role of aspartate and prephenate aminotransferase activities in
      plastid nitrogen metabolism.
AB  - Chloroplasts and plastids of nonphotosynthetic plant cells contain two aspartate
      (Asp) aminotransferases: a eukaryotic type (Asp5) and a prokaryotic-type
      bifunctional enzyme displaying Asp and prephenate aminotransferase activities
      (PAT). We have identified the entire Asp aminotransferase gene family in
      Nicotiana benthamiana and isolated and cloned the genes encoding the isoenzymes
      with plastidic localization: NbAsp5 and NbPAT. Using a virus-induced gene
      silencing approach, we obtained N. benthamiana plants silenced for NbAsp5 and/or
      NbPAT. Phenotypic and metabolic analyses were conducted in silenced plants to
      investigate the specific roles of these enzymes in the biosynthesis of essential
      amino acids within the plastid. The NbAsp5 silenced plants had no changes in
      phenotype, exhibiting similar levels of free Asp and glutamate as control plants,
      but contained diminished levels of asparagine and much higher levels of lysine.
      In contrast, the suppression of NbPAT led to a severe reduction in growth and
      strong chlorosis symptoms. NbPAT silenced plants exhibited extremely reduced
      levels of asparagine and were greatly affected in their phenylalanine metabolism
      and lignin deposition. Furthermore, NbPAT suppression triggered a transcriptional
      reprogramming in plastid nitrogen metabolism. Taken together, our results
      indicate that NbPAT has an overlapping role with NbAsp5 in the biosynthesis of
      Asp and a key role in the production of phenylalanine for the biosynthesis of
      phenylpropanoids. The analysis of NbAsp5/NbPAT cosilenced plants highlights the
      central role of both plastidic aminotransferases in nitrogen metabolism; however,
      only NbPAT is essential for plant growth and development. 

PMID- 24296075
TI  - Empowering village doctors and enhancing rural healthcare using cloud computing
      in a rural area of mainland China.
AB  - BACKGROUND: China's healthcare system often struggles to meet the needs of its
      900 million people living in rural areas due to major challenges in preventive
      medicine and management of chronic diseases. Here we address some of these
      challenges by equipping village doctors (ViDs) with Health Information Technology
      and developing an electronic health record (EHR) system which collects individual
      patient information electronically to aid with implementation of chronic disease
      management programs. METHODS: An EHR system based on a cloud-computing
      architecture was developed and deployed in Xilingol county of Inner Mongolia
      using various computing resources (hardware and software) to deliver services
      over the health network using Internet when available. The system supports the
      work at all levels of the healthcare system, including the work of ViDs in rural
      areas. An analysis done on 291,087 EHRs created from November 2008 to June 2011
      evaluated the impact the EHR system has on preventive medicine and chronic
      disease management programs in rural China. RESULTS: From 2008 to 2011 health
      records were created for 291,087 (26.25%) from 1,108,951 total Xilingol residents
      with 10,240 cases of hypertension and 1152 cases of diabetes diagnosed and
      registered. Furthermore, 2945 hypertensive and 305 diabetic patients enrolled in
      follow-up. Implementing the EHR system revealed a high rate of cholecystectomies
      leading to investigations and findings of drinking water contaminated with
      metals. Measures were taken to inform the population and clean drinking water was
      supplied. CONCLUSIONS: The cloud-based EHR approach improved the care provision
      for ViDs in rural China and increased the efficiency of the healthcare system to
      monitor the health status of the population and to manage preventive care
      efforts. It also helped discover contaminated water in one of the project areas
      revealing further benefits if the system is expanded and improved.

PMID- 24296074
TI  - Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine
      like actions at monoamine transporters.
AB  - Psychostimulants such as amphetamine and cocaine are illicitly used drugs that
      act on neurotransmitter transporters for dopamine, serotonin or norepinephrine.
      These drugs can by themselves already cause severe neurotoxicity. However, an
      additional health threat arises from adulterant substances which are added to the
      illicit compound without declaration. One of the most frequently added
      adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole.
      We tested the effects of levamisole on neurotransmitter transporters
      heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less
      potent than cocaine in blocking norepinephrine and dopamine uptake, and had only
      very low affinity for the serotonin transporter. In addition, levamisole did not
      trigger any appreciable substrate efflux. Because levamisole and cocaine are
      frequently co-administered, we searched for possible allosteric effects; at
      30MUM, a concentration at which levamisole displayed already mild effects on
      norepinephrine transport it did not enhance the inhibitory action of cocaine.
      Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which
      is classified as an amphetamine-like substance. We examined the uptake-inhibitory
      and efflux-eliciting properties of aminorex and found it to exert strong effects
      on all three neurotransmitter transporters in a manner similar to amphetamine. We
      therefore conclude that while the adulterant levamisole itself has only moderate
      effects on neurotransmitter transporters, its metabolite aminorex may exert
      distinct psychostimulant effects by itself. Given that the half-time of
      levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that
      after the cocaine effect "fades out" the levamisole/aminorex effect "kicks in". 

PMID- 24296076
TI  - Detection of phytochrome-like genes from Rhazya stricta (Apocynaceae) using de
      novo genome assembly.
AB  - Phytochrome-like genes in the wild plant species Rhazya stricta Decne were
      characterized using a de novo genome assembly of next generation sequence data.
      Rhazya stricta contains more than 100 alkaloids with multiple pharmacological
      properties, and leaf extracts have been used to cure chronic rheumatism, to treat
      tumors, and in the treatment of several other diseases. Phytochromes are known to
      be involved in the light-regulated biosynthesis of some alkaloids. Phytochromes
      are soluble chromoproteins that function in the absorption of red and far-red
      light and the transduction of intracellular signals during light-regulated plant
      development. De novo assembly of the nuclear genome of R. stricta recovered
      45,641 contigs greater than 1000bp long, which were used in constructing a local
      database. Five sequences belonging to Arabidopsis thaliana phytochrome gene
      family (i.e., AtphyABCDE) were used to identify R. stricta contigs with
      phytochrome-like sequences using BLAST. This led to the identification of three
      contigs with phytochrome-like sequences covering AtphyA-, AtphyC- and AtphyE-like
      full-length genes. Annotation of the three sequences showed that each contig
      consists of one phytochrome-like gene with three exons and two introns. BLASTn
      and BLASTp results indicated that RsphyA mRNA and protein sequences had
      homologues in Wrightia coccinea and and Solanum tuberosum, respectively. RsphyC
      like mRNA and protein sequence were homologous to Vitis vinifera and Vitis
      riparia. RsphyE-like mRNA coding and protein sequences were homologous to Ipomoea
      nil. Multiple-sequence alignment of phytochrome proteins indicated a homology
      with 30 sequences from 23 different species of flowering plants. Phylogenetic
      analysis confirmed that each R. stricta phytochrome gene is related to the same
      phytochrome gene of other flowering plants. It is proposed that the absence of
      phyB gene in R. stricta is due to RsphyA gene taking over the role of phyB.

PMID- 24296077
TI  - Rapid identification of potential drought tolerance genes from Solanum tuberosum
      by using a yeast functional screening method.
AB  - Identification of major stress tolerance genes of a crop plant is important for
      the rapid development of its stress-tolerant cultivar. Here, we used a yeast
      functional screen method to identify potential drought-tolerance genes from a
      potato plant. A cDNA expression library was constructed from hyperosmotic
      stressed potato plants. The yeast transformants expressing different cDNAs were
      selected for their ability to survive in hyperosmotic stress conditions. The
      relative tolerances of the selected yeast transformants to multiple abiotic
      stresses were also studied. Specific potato cDNAs expressed in the tolerant yeast
      transformants were identified. Sixty-nine genes were found capable of enhancing
      hyperosmotic stress tolerance of yeast. Based on the relative tolerance data
      generated, 12 genes were selected, which could be most effective in imparting
      higher drought tolerance to potato with better survival in salt and high
      temperature stresses. Orthologues of few genes identified here are previously
      known to increase osmotic stress tolerance of yeast and plants; however, specific
      studies are needed to confirm their role in the osmotic stress tolerance of
      potato.

PMID- 24296078
TI  - Thymoquinone causes multiple effects, including cell death, on dividing plant
      cells.
AB  - Thymoquinone (TQ) is a major constituent of Nigella sativa oil with reported anti
      oxidative activity and anti-inflammatory activity in animal cells. It also
      inhibits proliferation and induces programmed cell death (apoptosis) in human
      skin cancer cells. The present study sought to detect the influence of TQ on
      dividing cells of three plant systems and on expression of Bcl2-associated
      athanogene-like (BAG-like) genes that might be involved during the process of
      cell death. BAG genes are known for the regulation of diverse physiological
      processes in animals, including apoptosis, tumorigenesis, stress responses, and
      cell division. Synthetic TQ at 0.1mg/mL greatly reduced wheat seed germination
      rate, whereas 0.2mg/mL completely inhibited germination. An Evans blue assay
      revealed moderate cell death in the meristematic zone of Glycine max roots after
      1h of TQ treatment (0.2mg/mL), with severe cell death occurring in this zone
      after 2h of treatment. Light microscopy of TQ-treated (0.2mg/mL) onion hairy root
      tips for 1h revealed anti-mitotic activity and also cell death-associated
      changes, including nuclear membrane disruption and nuclear fragmentation.
      Transmission electron microscopy of TQ-treated cells (0.2mg/mL) for 1h revealed
      shrinkage of the plasma membrane, leakage of cell lysate, degradation of cell
      walls, enlargement of vacuoles and condensation of nuclei. Expression of one BAG
      like gene, previously associated with cell death, was induced 20 min after TQ
      treatment in Glycine max root tip cells. Thus, TQ has multiple effects, including
      cell death, on dividing plant cells and plants may serve as a useful system to
      further investigate the mechanisms underlying the response of eukaryotic cells to
      TQ.

PMID- 24296079
TI  - Isolation and characterization of rhizosphere bacteria for the biocontrol of the
      damping-off disease of tomatoes in Tunisia.
AB  - Fluorescent Pseudomonas spp., isolated from tomato and pepper plants rhizosphere
      soil, was evaluated in vitro as a potential antagonist of fungal pathogens.
      Pseudomonas strains were tested against the causal agents of tomatoes damping-off
      (Sclerotinia sclerotiorum), root rot (Fusarium solani), and causal agents of stem
      canker and leaf blight (Alternaria alternata). For this purpose, dual culture
      antagonism assays were carried out on 25% tryptic soy agar, King B medium and
      potato dextrose agar to determine the effect of the strains on mycelial growth of
      the pathogens. In addition, strains were screened for their ability to produce
      exoenzymes and siderophores. All the strains significantly inhibited Alternaria
      alternata, particularly in 25% TSA medium. Antagonistic effect on Sclerotinia
      sclerotiorum and Fusarium solani was greater on King B medium. Protease was
      produced by 30% of the strains, but no strain produced cellulase or chitinase.
      Finally, the selected Pseudomonas strain, Psf5, was evaluated on tomato seedling
      development and as a potential candidate for controlling tomato damping-off
      caused by Sclerotinia sclerotiorum, under growth chamber conditions. In vivo
      studies resulted in significant increases in plant stand as well as in root dry
      weight. Psf5 was able to establish and survive in tomato plants rhizosphere after
      40days following the planting of bacterized seeds.

PMID- 24296080
TI  - Chemotaxis with directional sensing during Dictyostelium aggregation.
AB  - We show that the chemotactic movements of colonies of the starving amoeba
      Dictyostelium discoideum are driven by a force that depends on both the direction
      of propagation (directional sensing) of reaction-diffusion chemotactic waves and
      on the gradient of the concentration of the chemoattractant, solving the
      chemotactic wave paradox. It is shown that the directional sensing of amoebae is
      due to the sensitivity of the cells to the time variation of the concentration of
      the chemoattractant combined with its spatial gradient. It is also shown that
      chemotaxis exclusively driven by local concentration gradient leads to unstable
      local motion, preventing cells from aggregation. These findings show that the
      formation of mounds, which initiate multicellularity in Dictyostelium discoideum,
      is caused by the sensitivity of the amoebae due to three factors, namely, to the
      direction of propagation of the chemoattractant, to its spatial gradient, and to
      the emergence of cAMP "emitting centres", responsible for the local accumulation
      of the amoebae.

PMID- 24296081
TI  - Thermotolerance and regeneration in the brittle star species complex Ophioderma
      longicauda: a preliminary study comparing lineages and Mediterranean basins.
AB  - Global warming is expected to change marine species distributions; it is thus
      critical to understand species current thermotolerance. The brittle star species
      complex Ophioderma longicauda comprises a broadcast spawning lineage L1 and a
      brooding lineage L3. We collected L1 specimens from Marseilles and Crete, and L3
      specimens from Crete. We monitored survival, autotomy and arm regeneration at 17,
      26 and 30 degrees C during 14 weeks. Globally O. longicauda showed good
      resistance to elevated temperatures compared to other published studies on
      ophiuroids. The L3 sample displayed a better thermotolerance than L1 samples.
      Yet, more research is needed to establish whether these differences are due to
      lineages, geographic origin, or random effects. We provided for the first time
      individual regeneration trajectories, and showed that regeneration followed a
      growth curve and was highly influenced by temperature in both lineages. Our
      results highlight the importance of taking into account the presence of cryptic
      species when studying the potential effects of global warming.

PMID- 24296082
TI  - A study of the relict fish fauna of northern Chad, with the first records of a
      polypterid and a poeciliid in the Sahara desert.
AB  - Seventeen species and sub-species of fishes belonging to four families
      (Cyprinidae, Clariidae, Aplocheilidae, Cichlidae) were known to occur in
      perennial bodies of water in the Sahara desert. The study of fishes collected in
      Lake Boukou near Ounianga Serir (Borkou, northern Chad) shows, for the first
      time, the occurrence in the Sahara desert of relict populations of Polypterus
      senegalus (Polypteridae) and Poropanchax normani (Poeciliidae). The Cichlidae
      Tilapia zilli was also collected in this lake. With these new records, the relict
      fish fauna currently known in lakes and gueltas of the Borkou plateaus comprises
      six species. In the Ennedi Mountains, where the specific status of Barbus
      populations was unclear, B. macrops was collected in Bachikere guelta. The toad
      Amietophrynus regularis was collected in Ounianga Kebir.

PMID- 24296083
TI  - Feasibility of baculovirus-mediated reporter gene delivery for efficient
      monitoring of islet transplantation in vivo.
AB  - OBJECTIVE: The objective of this study was to explore the feasibility of
      baculovirus vector-mediated sodium iodide symporter (NIS) gene delivery to
      monitor islet transplantation. METHODS: Baculovirus vectors expressing green
      fluorescent protein (GFP) or NIS (Bac-GFP and Bac-NIS) were established using the
      Bac-to-Bac baculovirus expression system. The GFP expression of Bac-GFP-infected
      rat islets was observed in vitro by fluorescence microscopy. Iodine uptake and
      inhibition of iodine uptake by NaClO4 in Bac-NIS-infected islets were dynamically
      monitored in vitro. Bac-GFP- or Bac-NIS-infected islets were implanted into the
      left axillary cavity of NOD-SCID mice, and fluorescence imaging and (125)I
      NanoSPECT/CT imaging were subsequently performed in vivo. RESULTS: Bac-GFP
      efficiently infected rat islets (over 95% infected at MOI=40), and the expression
      of GFP lasted approximately two weeks. NaClO4 could inhibit iodine uptake by Bac
      NIS-infected islets. In vivo imaging revealed that the fluorescence intensity of
      the transplant sites in Bac-GFP-infected groups was significantly higher than in
      the non-infected group. Grafts could be clearly observed by (125)I NanoSPECT/CT
      imaging for up to 8 h. CONCLUSION: Baculovirus vectors are powerful vehicles for
      studying rat islets in gene delivery. It is feasible to use a baculovirus vector
      to delivery an NIS gene for non-invasive monitoring transplanted islets in vivo
      by the expression of the target gene.

PMID- 24296085
TI  - Clinical trials of traditional Chinese medicine in the treatment of diabetic
      nephropathy--a systematic review based on a subgroup analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The purpose of this study is to systematically
      evaluate the efficacy of traditional Chinese medicine (TCM) decoctions with
      different ingredients in the treatment of diabetic nephropathy (DN). MATERIALS
      AND METHODS: Papers obtained after the retrieval of randomized controlled
      clinical trials (RCTs) of TCM treatments of diabetic nephropathy through online
      database (e.g. Medline, CBM, CNKI, VIP, the online database of Chinese medicine,
      CDFD, CMFD, and CENTRAL FROM Cochrane Library, etc.) as well as research data in
      our library. They were published between January 2001 and December 2012.
      According to the categories of the main TCM ingredients, all the cases in the
      literature were divided into a liver-kidney YIN deficiency group, a QI-BLOOD YIN
      and-YANG deficiency group, and a spleen-kidney YANG deficiency group. Stata 11.0
      was applied for subgroup analysis. RESULTS: A total of 21 Chinese RCTs were
      included in this review. The Q values of the three groups were 13.18, 0.25 and
      3.27, respectively, P>0.05, and thus, there was no clinical heterogeneity. The
      combined relative risk (RR) value and its 95% confidence interval were 1.48
      (1.37, 1.60), 1.19 (1.06, 1.34), and 1.33 (1.19, 1.50), respectively, P<0.05.
      CONCLUSIONS: Compared with the qi-blood yin-and-yang deficiency group and the
      spleen-kidney yang deficiency group, the liver-kidney yin deficiency group has
      better prospects in clinical application to ensure renal function during the
      treatment of DN, and this possibility is worthy of further study.

PMID- 24296084
TI  - Screening preeclamptic cord plasma for proteins associated with decreased breast
      cancer susceptibility.
AB  - Preeclampsia, a complication of pregnancy characterized by hypertension and
      proteinuria, has been found to reduce the subsequent risk for breast cancer in
      female offspring. As this protective effect could be due to exposure to
      preeclampsia-specific proteins during intrauterine life, the proteomic profiles
      of umbilical cord blood plasma between preeclamptic and normotensive pregnancies
      were compared. Umbilical cord plasma samples, depleted of 14 abundant proteins,
      were subjected to proteomic analysis using the quantitative method of nanoACQUITY
      ultra performance liquid chromatography-mass spectrometry with elevated energy
      mode of acquisition(E) (NanoUPLC-MS(E)). Sixty-nine differentially expressed
      proteins were identified, of which 15 and 6 proteins were only detected in
      preeclamptic and normotensive pregnancies, respectively. Additionally, expression
      of 8 proteins (gelsolin, complement C5, keratin type I cytoskeletal 10, pigment
      epithelium-derived factor, complement factor B, complement component C7,
      hemoglobin subunit gamma-2 and alpha-fetoprotein) were up-regulated in
      preeclampsia with a fold change of >=2.0 when compared to normotensive
      pregnancies. The identification of alpha-fetoprotein in preeclamptic umbilical
      cord blood plasma supported the validity of this screen as alpha-fetoprotein has
      anti-estrogenic properties and has previously been linked to preeclampsia as well
      as a reduced breast cancer risk. The findings of this pilot study may provide new
      insights into the mechanistic link between preeclampsia and potentially reduced
      breast cancer susceptibility in adult life.

PMID- 24296086
TI  - The neuroprotective effect of modified "Shengyu" decoction is mediated through an
      anti-inflammatory mechanism in the rat after traumatic brain injury.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: "Shengyu" decoction, a traditional Chinese
      medicine, has been used to treat diseases with deficit in "qi" and "blood"
      induced frequently by profound loss of blood or by long sores with heavy pus, in
      which a potential anti-inflammatory effect is implied. The modified "Shengyu"
      decoction (MSD) used in the present study was designed on the basis of the
      "Shengyu" decoction, additional four herbs were added in. Many ingredients in
      these herbs have been demonstrated to be anti-inflammatory and thus MSD may be
      used for the treatment of traumatic brain injury (TBI). To evaluate the
      neuroprotective effect and the underlying mechanisms of MSD on the rat brain
      after TBI. MATERIALS AND METHODS: TBI was induced in the right cerebral cortex of
      male adult rats using Feeney's weight-drop method. The rats were administered a
      gavage of MSD (0.5, 1.0 or 2.0 ml/200 g) 6h after TBI. The neurological
      functions, brain water content, contusion volume, and neuron loss were
      determined. The levels of TNF-alpha, IL-1beta, IL-6, and IL-10 and the number of
      GFAP- and Iba1-positive cells in the brain ipsilateral to TBI were also measured.
      Moreover, the influence of MSD on these variables was observed at the same time.
      RESULTS: The neurological deficits, brain water content, and neuron loss were
      significantly reduced after 1.0 or 2.0 ml/200 g of MSD treatment but not after
      0.5 ml/200 g. In addition, treatment with MSD (1.0 ml/200 g) significantly
      increased the level of IL-10 and reduced the level of TNF-alpha and IL-1beta and
      the number of GFAP- and Iba1-positive cells after TBI. However, the contusion
      volume of brain tissue and the expression of IL-6 were not significantly changed.
      CONCLUSION: MSD may be a potential therapeutic for the treatment of TBI because
      MSD alleviated secondary brain injury induced by TBI. In addition, MSD inhibited
      the inflammatory response through reducing the expression of inflammatory
      cytokines and the activation of microglial cells and astrocytes in the brain
      tissue of rats after TBI. Therefore, a potential anti-inflammatory mechanism of
      the "Shengyu" decoction was confirmed, which may be one of the main reasons of
      "Shengyu" decoction used to treat diseases with obvious inflammatory responses.

PMID- 24296087
TI  - Traditional use of the native medicinal plant resource of Mt. Rtanj (Eastern
      Serbia): ethnobotanical evaluation and comparison.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study reports on the uses of medicinal
      plants and ethnobotanical significance of Mt. Rtanj, Eastern Serbia. The aim of
      the study was collecting information on plant utilization and creating the list
      of medicinal plants collected by local community in the region of Rtanj Mt. in
      Serbia. METHODOLOGY: A group of generally elderly people from the region were
      interviewed, asked to identify a certain number of plant taxa used against
      various human ailments. A quantitative ethnobotanical comparison has been
      performed in relation to other studies concerning the central Balkan Peninsula.
      RESULTS: There is an inventory of 45 plant species recorded. At the family level,
      the most common in traditional usage were species of Labiatae (22%), Rosaceae
      (20%) and Compositae (13%). The results of the survey suggested that Hypericum
      perforatum was the most popular medicinal plant. Among the 7 different recorded
      types of preparation, the aerial parts of plants were the most popular (47.3%).
      The most frequently reported medicinal uses of herbal drugs include remedies for
      immune system (22.97%), respiratory system (15.77%) and digestive system
      disorders (15.32%). However, a comparatively small number of available plant
      species was used for medicinal purposes while the level of ethnobotanical
      diversity was lower when compared to adjacent regions. CONCLUSIONS:
      Ethnobotanical knowledge in this area is decreasing due to high emigration rates
      during the last period. The historically developed ethnobotanical heritage should
      be preserved and promoted on the larger level, getting the special position in
      the future management plans for this area.

PMID- 24296088
TI  - Bioactivity-guided isolation of polyacetylenes with inhibitory activity against
      NO production in LPS-activated RAW264.7 macrophages from the rhizomes of
      Atractylodes macrocephala.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes macrocephala
      (Compositae) is one of the most well-known traditional Chinese medicine in China,
      Japan and Korea, which has a long history of use for the treatment of splenic
      asthenia, edema, anorexia, and excessive perspiration, etc. As active compounds
      of anti-inflammatory activity of this medicinal plant have not been fully
      elucidated, the aim of this study was to isolate and identify the active
      constituents inhibiting nitric oxide (NO) production from the rhizomes of A.
      macrocephala. MATERIALS AND METHODS: Inhibitory activity against NO production in
      lipopolysaccharide-activated RAW264.7 macrophages was evaluated by Griess
      reaction. Fifteen polyacetylenes were isolated from the active ethyl acetate
      extract using activity-guided screening. The structures of all compounds were
      elucidated by spectroscopic methods and comparison with published data. The
      compounds were further tested for their inhibitory activity against NO
      production. RESULTS: Seven new polyacetylenes, named atractylodemaynes A-G (1-7),
      along with eight known ones (8-15) were isolated. Compound 14 was isolated for
      the first time from the rhizomes of A. macrocephala. The study showed that the
      tested compounds exhibited inhibitory activity against NO production in a dose
      dependent manner. Among them, compounds 10, 11 and 12 had relatively stronger
      inhibitory effect with IC50 values of 28, 23 and 19MUM, respectively. CONCLUSION:
      The results demonstrated that the polyacetylenes might greatly contribute to the
      anti-inflammatory activity of the rhizomes of A. macrocephala.

PMID- 24296089
TI  - Eucommia ulmoides Oliv.: ethnopharmacology, phytochemistry and pharmacology of an
      important traditional Chinese medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. (Family Eucommiaceae),
      also known as Du-zhong (Chinese: ), Tuchong (in Japanese), is the sole species of
      the genus Eucommia. The leaf, stem, and bark as well as staminate flower of
      Eucommia ulmoides have been traditionally used to cure many diseases in China,
      Japan, Korea, among others. The aim of this review is to comprehensively outline
      the botanical description, ethnopharmacology, phytochemistry, biological
      activities, and toxicology of Eucommia ulmoides and to discuss possible trends
      for further study of Eucommia ulmoides. MATERIALS AND METHODS: Information on
      Eucommia ulmoides was gathered via the internet (using Pub Med, Elsevier, Baidu
      Scholar, Google Scholar, Medline Plus, ACS, CNKI, and Web of Science) and from
      books in local libraries. RESULTS: One-hundred twelve compounds of Eucommia
      ulmoides, including the main active constituents, lignans and iridoids, have been
      isolated and identified. In vitro and in vivo studies indicated that monomer
      compounds and extracts from Eucommia ulmoides possess wide-ranging
      pharmacological actions, especially in treating hypertension, hyperlipemia,
      diabetes, obesity, sexual dysfunction, osteoporosis, Alzheimer's disease, aging,
      lupus-like syndrome, and immunoregulation. CONCLUSIONS: Eucommia ulmoides has
      been used as a source of traditional medicine and as a beneficial health food.
      Phytochemical and pharmacological studies of Eucommia ulmoides have received much
      interest, and extracts and active compounds continue to be isolated and proven to
      exert various effects. Further toxicity and clinical studies are warranted to
      establish more detailed data on crude extracts and pure compounds, enabling more
      convenient preparations for patients. Therefore, this review on the
      ethnopharmacology, phytochemistry, biological activities, and toxicity of
      Eucommia ulmoides will provide helpful data for further studies as well as the
      commercial exploitation of this traditional medicine.

PMID- 24296090
TI  - Magnesium lithospermate B improves myocardial function and prevents simulated
      ischemia/reperfusion injury-induced H9c2 cardiomyocytes apoptosis through Akt
      dependent pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Magnesium lithospermate B (MLB), an active
      polyphenol acid of Radix Salviae Miltiorrhizae (Danshen), showed a wide range of
      pharmacological activities in cardiovascular diseases. However, its role in
      protection against ischemia/reperfusion injury in H9c2 cardiomyocytes has not
      been elucidated. This study was aimed to investigate the protective effect and
      potential molecular mechanisms of MLB on apoptosis in H9c2 cardiomyocytes in
      vitro. MATERIALS AND METHODS: We tested cell viability, shortening amplitude,
      necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2
      and Bax after 2-h simulated ischemia and 24-h simulated reperfusion in H9c2
      cardiomyocytes. We further observed the contractile function in hearts after they
      were subjected to global 30-min ischemia and 180-min reperfusion. RESULTS:
      Pretreatment with MLB markedly increased cell viability and while reducing
      evidence of necrosis and apoptosis in H9c2 cardiomyocytes. In addition, the
      expression of Bcl-2 and Bax protein was modulated. The results also showed that
      MLB significantly increased phosphorylation of Akt and that this phosphorylation
      can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor.
      Furthermore, MLB improved MI/R-induced myocardial contractile function.
      CONCLUSION: Our results showed that MLB prevents I/R-induced myocardial damage by
      reducing necrosis and apoptosis in H9c2 cardiomyocytes and improving myocardial
      function in rat hearts.

PMID- 24296092
TI  - Southwestern Surgical Congress presidential address 2013.

PMID- 24296091
TI  - Regional expression of extracellular signal-regulated kinase 1 and 2 mRNA in a
      morphine-induced conditioned place preference model.
AB  - Chronic morphine administration has been shown to change the expression of
      extracellular signal-regulated kinase (ERK), which is a molecule known to play an
      important role in homeostatic adaptations caused by addictive drugs. In the
      present study, we investigated the expression of ERK messenger ribonucleic acid
      (mRNA) of the prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus, and
      caudate putamen (CPu) in morphine-induced conditioned place preference (CPP) by
      real-time reverse transcriptase polymerase chain reaction (real-time PCR). CPP
      was established by alternate morphine (10 mg/kg) injections, extinguished after a
      10-day extinction training, and reinstated by a priming injection of morphine (10
      mg/kg). During three phases of morphine-induced CPP, the expression levels of
      ERK1 and ERK2 mRNA were altered in various brain regions. In the PFC, the
      expression levels of ERK1 and ERK2 mRNA were increased after chronic morphine
      injection (p=0.003, p=0.000), and did not return to the basal level after
      extinction training (p=0.025, p=0.000), but decreased after a priming injection
      (p=0.000, p=0.000). In the CPu, ERK1 mRNA had an abrupt increase following a
      priming injection (p=0.000). Different from other brain regions, the expression
      levels of ERK1 and ERK2 mRNA were decreased in three phases of morphine-induced
      CPP in the hippocampus (ERK1: p=0.000, p=0.040, p=0.000; ERK2: p=0.000, p=0.000,
      p=0.000, respectively). These results suggest region-specific changes of ERK1 and
      ERK2 mRNA expression during morphine-induced CPP.

PMID- 24296093
TI  - Disruptive technology in the treatment of thoracic trauma.
AB  - The care of patients with thoracic injuries has undergone monumental change over
      the past 25 years. Advances in technology have driven improvements in care, with
      obvious benefits to patients. In many instances, new or "disruptive" technologies
      have unexpectedly displaced previously established standards for the diagnosis
      and treatment of these potentially devastating injuries. Examples of disruptive
      technology include the use of ultrasound technology for the diagnosis of cardiac
      tamponade and pneumothorax; thoracoscopic techniques instead of thoracotomy,
      pulmonary tractotomy, and stapled lung resection; endovascular repair of thoracic
      aortic injury; operative fixation of flail chest; and the enhanced availability
      of extracorporeal lung support for severe respiratory failure. Surgeons must be
      prepared to recognize the benefits, and limits, of novel technologies and
      incorporate these methods into day-to-day treatment protocols. 

PMID- 24296094
TI  - Innovations in geriatric trauma and resident research education: bridging the
      gap.
AB  - The recent history of changes in the geriatric population in the US, the unique
      vulnerability to different mechanisms of trauma and the need for innovative
      management strategies to address them are discussed using the Geriatric "G-60"
      service as an illustration. The issue is not whether geriatric trauma "G-60" is
      coming; G-60 is here. A short detour into my own research experience is presented
      not as prescription but guidance for the development of futures cadres of
      surgeons. Resident research is not a luxury but key to transforming knowledge
      from benchside to bedside and back. 

PMID- 24296095
TI  - Neoadjuvant therapy and breast cancer surgery: a closer look at postoperative
      complications.
AB  - BACKGROUND: Neoadjuvant therapy is important in the treatment of advanced breast
      cancer. METHODS: Postoperative complications in neoadjuvant patients were
      analyzed. RESULTS: One hundred forty patients underwent 148 breast cancer
      surgeries after neoadjuvant therapy: 28% breast-conserving therapy procedures,
      36% mastectomies, 28% mastectomies with immediate reconstruction, and 8%
      mastectomies with delayed reconstruction. Forty-seven patients (34%) suffered 59
      complications: 18% of those undergoing breast-conserving therapy, 30% of those
      undergoing mastectomy, 44% of those undergoing mastectomy with immediate
      reconstruction, and 67% of those undergoing mastectomy with delayed
      reconstruction. Major complications occurred in 18% of patients. Skin loss
      occurred in 6% of patients. One patient had partial nipple necrosis. Three
      patients suffered implant loss. One patient had deep inferior epigastric artery
      perforator flap loss. Eleven hematomas and 5 infectious complications required
      reoperation. CONCLUSIONS: Surgery after neoadjuvant therapy is safe, but careful
      counseling is warranted given that 18% of patients experienced major
      complications. Complications rates are higher with reconstruction, but feared
      complications of skin, nipple, implant, or flap loss were infrequent.

PMID- 24296096
TI  - Vasopressor use after initial damage control laparotomy increases risk for
      anastomotic disruption in the management of destructive colon injuries.
AB  - BACKGROUND: Management of destructive colon injuries during damage control (DC)
      laparotomy is debated. The authors reviewed a single institution's experience
      with destructive colon injuries to identify risk factors for anastomotic failure
      after colon reconstruction. METHODS: The authors identified all trauma patients
      sustaining destructive colon injuries between 2002 and 2011 from their medical
      center's trauma registry. Anastomotic leak was defined as suture or staple line
      disruption or enteral fistula formation. RESULTS: Of 171 identified patients, 68
      had DC procedures, 41 (60%) had subsequent anastomoses performed during the same
      hospitalization, and 27 (40%) were diverted. The colon anastomotic leak rate in
      patients who underwent DC laparotomy was higher than in patients who were
      reconstructed at the primary operation in a non-DC setting (17% vs 6%, P = .09).
      The use of vasopressors after the initial DC operation more than quadrupled the
      leak rate to 50% (P = .02). CONCLUSIONS: Colonic anastomotic disruptions yield
      deadly consequences, and diversion rather than anastomosis should be used in
      patients who require vasopressor support after the initial DC procedure.

PMID- 24296097
TI  - A small amount can make a difference: a prospective human study of the
      paradoxical coagulation characteristics of hemothorax.
AB  - BACKGROUND: The evacuated hemothorax has been poorly described because it varies
      with time, it has been found to be incoagulable, and its potential effect on the
      coagulation cascade during autotransfusion is largely unknown. METHODS: This is a
      prospective descriptive study of adult patients with traumatic chest injury
      necessitating tube thoracostomy. Pleural and venous samples were analyzed for
      coagulation, hematology, and electrolytes at 1 to 4 hours after drainage. Pleural
      samples were also analyzed for their effect on the coagulation cascade via mixing
      studies. RESULTS: Thirty-four subjects were enrolled with a traumatic hemothorax.
      The following measured coagulation factors were significantly depleted compared
      with venous blood: international normalized ratio (>9 vs 1.1) (P < .001) and
      activated partial thromboplastin time (aPTT) (>180 vs 24.5 seconds) (P < .001).
      Mixing studies showed a dose-dependent increase in coagulation dilutions through
      1:8 (P < .05). CONCLUSIONS: An evacuated hemothorax does not vary in composition
      significantly with time and is incoagulable alone. Mixing studies with hemothorax
      plasma increased coagulation, raising safety concerns.

PMID- 24296098
TI  - Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the
      answer?
AB  - BACKGROUND: Inadequate anti-factor Xa levels and increased venous thromboembolic
      events occur in trauma patients receiving standard prophylactic enoxaparin
      dosing. The aim of this study was to test the hypothesis that higher dosing (40
      mg twice daily) would improve peak anti-Xa levels and decrease venous
      thromboembolism. METHODS: A retrospective review was performed of trauma patients
      who received prophylactic enoxaparin and peak anti-Xa levels over 27 months.
      Patients were divided on the basis of dose: group A received 30 mg twice daily,
      and group B received 40 mg twice daily. Demographics and rates of venous
      thromboembolism were compared between dose groups and patients with inadequate or
      adequate anti-Xa levels. RESULTS: One hundred twenty-four patients were included,
      90 in group A and 34 in group B. Demographics were similar, except that patients
      in group B had a higher mean body weight. Despite this, only 9% of group B
      patients had inadequate anti-Xa levels, compared with 33% of those in group A (P
      = .01). Imaging studies were available in 69 patients and revealed 8 venous
      thromboembolic events (P = NS, group A vs group B) with significantly more venous
      thromboembolic events occurring in patients with low anti-Xa levels (P = .02).
      CONCLUSIONS: Although higher dosing of enoxaparin led to improved anti-Xa levels,
      this did not equate to a statistical decrease in venous thromboembolism.

PMID- 24296099
TI  - Readmission following open ventral hernia repair: incidence, indications, and
      predictors.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence, indications, and
      predictive factors of hospital readmission after open ventral hernia repair.
      METHODS: A retrospective review of all open ventral hernia repairs at a single
      institution from 2000 to 2010 was performed to assess readmissions between 1 to
      30, 1 to 90, and 91 to 365 days. Multivariate analysis was performed to identify
      independent predictors of 30-day readmission. RESULTS: Of the 888 patients, 75
      (8%) were readmitted between 1 and 30 days, 97 (11%) between 1 and 90 days, and
      78 (9%) between 91 and 365 days. Unplanned readmissions related to the surgery
      constituted the majority of 1-day to 30-day and 1-day to 90-day readmissions (82%
      and 74%, respectively) but not between 91 and 365 days (32%). Prior superficial
      or deep surgical-site infection (odds ratio, 2.39; 95% confidence interval, 1.32
      to 4.32) and duration of surgery (odds ratio, 1.35; 95% confidence interval, 1.05
      to 1.73) were associated with 30-day readmission. CONCLUSIONS: Efforts to reduce
      readmissions should be directed at modifiable risk factors for surgical-site
      infection and other surgical complications, particularly among those with prior
      skin infections and longer durations of surgery.

PMID- 24296100
TI  - Determinants of surgical decision making: a national survey.
AB  - BACKGROUND: We conducted a national survey of general surgeons to address the
      association between surgeon characteristics and the tendency to recommend
      surgery. METHODS: We used a web-based survey with 25 hypothetical clinical
      scenarios with clinical equipoise regarding the decision to operate. The
      respondent-level tendency to operate (TTO) score was calculated as the average
      score over the 25 scenarios. Surgical volume was based on self-report. Linear
      regression models were used to evaluate the associations between TTO, other
      covariates of interest, and surgical volume. RESULTS: There were 907 respondents.
      The mean surgical TTO was 3.05 +/- .43. Surgeons had significantly lower TTO
      scores when responding to questions within their area of practice (P < .0001).
      There was no association between TTO and malpractice concerns, financial
      incentives, or compensation structure. CONCLUSIONS: Surgeons recommend
      intervention far less frequently within their area of specialization. Malpractice
      concerns, volume, and financial compensation do not significantly affect surgical
      decision making.

PMID- 24296101
TI  - Goal directed fluid resuscitation decreases time for lactate clearance and
      facilitates early fascial closure in damage control surgery.
AB  - BACKGROUND: Damage-control surgery frequently results in open abdomen. The
      objective of this study was to determine whether resuscitation with goal-directed
      fluid therapy (GDT) using "dynamic" hemodynamic indices via modern pulse contour
      analysis devices such as the FloTrac Vigileo monitor leads to lower fluid
      requirements, subsequent quicker abdominal closure, and overall improved outcomes
      in these patients. METHODS: Patients admitted to the surgical intensive care unit
      with open abdomen were retrospectively reviewed. Those resuscitated with Vigileo
      guided GDT were matched to those resuscitated by static clinical parameters.
      RESULTS: Total fluid intake and vasopressor requirements were similar in both
      groups. GDT with the Vigileo allowed earlier lactate clearance and reduced the
      number of days until abdominal wall closure by an average of .99 days.
      CONCLUSIONS: Vigileo-mediated GDT did not affect fluid volume or vasopressor use
      in open abdomen patients, but facilitated more effective resuscitation and
      decreased the number of days to fascial closure, leading to shorter hospital
      stays. Vigileo-mediated GDT, therefore, may improve overall outcomes in open
      abdomen patients.

PMID- 24296102
TI  - Pneumomediastinum: etiology and a guide to diagnosis and treatment.
AB  - BACKGROUND: Pneumomediastinum may be associated with mediastinal organ injury.
      The aim of this study was to identify predictive factors of mediastinal organ
      injury in patients with pneumomediastinum to guide diagnosis and treatment.
      METHODS: A retrospective review was conducted including patients aged >=18 years
      with Current Procedural Terminology code 518.1 (interstitial emphysema) from 2005
      2011. RESULTS: There were 279 of 343 patients (81%) with and 64 of 343 (19%)
      without history of trauma. In the trauma population, 13 patients (5%) were found
      to have mediastinal organ injuries, 10 (4%) had airway injuries, and 3 (1%) had
      esophageal injuries. In the nontrauma population, 36 patients (56%) had
      spontaneous pneumomediastinum, esophageal injuries were seen in 17 (27%),
      pneumothorax in 9 (14%), and airway injuries in 2 (3%). The predictors of
      esophageal injury were instrumentation (odds ratio [OR], 45.7; P < .0001),
      pleural effusion (OR, 10.5; P < .0001), and vomiting (OR, 9.3; P < .0001).
      Previous instrumentation was the most significant predictor of airway injury (OR,
      9.05; P < .02). CONCLUSIONS: Mediastinal organ injury in patients with
      pneumomediastinum is uncommon. Patients presenting with pneumomediastinum without
      a history of instrumentation, pleural effusion, or vomiting most commonly do not
      have mediastinal organ injuries.

PMID- 24296103
TI  - Blood transfusions in colorectal cancer surgery: incidence, outcomes, and
      predictive factors: an American College of Surgeons National Surgical Quality
      Improvement Program analysis.
AB  - BACKGROUND: Data analyzing the short-term outcomes and predictors of blood
      transfusions (BTs) in colorectal cancer (CRC) surgery are limited. METHODS: The
      American College of Surgeons National Surgical Quality Improvement Program (2005
      to 2010) was retrospectively reviewed for CRC cases performed with or without BT.
      Patient demographics, comorbidities, and operative variables were analyzed.
      Multivariate regression analysis was performed examining the effect of BT on
      outcomes. The LASSO algorithm for logistic regression was used to build a
      predictive model for BT taking into account preoperative and operative variables.
      RESULTS: A total of 27,120 patients underwent CRC, and 3,815 (14.07%) had BTs.
      Transfusions were associated with increased mortality (odds ratio [OR], 1.78),
      morbidity (OR, 2.38), length of stay (mean difference, 3.52 days), pneumonia (OR,
      2.70), and surgical-site infection (OR, 1.45). This effect was "dose dependent,"
      as patients receiving >=3 U of blood had increased morbidity (OR, 1.53), lengths
      of stay (mean difference, 1.82 days), pneumonia (OR, 2.52), and surgical-site
      infections (OR, 1.60) compared with those receiving 1 to 2 U. Predictors of BT
      were hematocrit <38%, open surgery, proctectomy, low platelet count, American
      Society of Anesthesiologists class IV or V, total colectomy, metastatic cancer,
      emergency, ascites, and infection. All P values were < .05. CONCLUSIONS: BTs are
      associated with worse short-term outcomes after CRC surgery. Knowledge of
      predictive factors will help in risk stratification and counseling.

PMID- 24296104
TI  - Polymorphisms of human placental alkaline phosphatase are associated with in
      vitro fertilization success and recurrent pregnancy loss.
AB  - Fertility is a quantitative, complex character governed by a considerable number
      of genes. Despite clinical and scientific advances, several cases of human
      infertility remain unexplained. In the present study, using a positional cloning
      approach in a mouse model of interspecific recombinant lines, a candidate gene,
      ALPP, encoding the placental alkaline phosphatase, was identified as being
      potentially involved in recurrent spontaneous abortion. We then analyzed patients
      for detecting putative associations between ALPP polymorphisms, in vitro
      fertilization failures, and miscarriages. ALPP was sequenced in 100 controls and
      100 patients affected by recurrent spontaneous abortion, from the same ethnic
      background. The frequency of several alleles and allelic combinations were
      different between recurrent spontaneous abortion and control women. One
      polymorphism induced a coding substitution (Ile89Leu) that was associated with a
      decreased risk of abortion and in vitro fertilization failure. Thereafter, the
      population was increased by the analysis of 92 additional controls and 612
      additional patients for the coding polymorphism Ile89Leu. We finally show, by
      functional analysis, that the 89Leu placental alkaline phosphatase has an
      enhanced alkaline phosphatase activity. This study suggests that ALPP genotyping
      could be a strong predictor of implantation success. 

PMID- 24296105
TI  - A model to predict deflection of bevel-tipped active needle advancing in soft
      tissue.
AB  - Active needles are recently being developed to improve steerability and placement
      accuracy for various medical applications. These active needles can bend during
      insertion by actuators attached to their bodies. The bending of active needles
      enables them to be steered away from the critical organs on the way to target and
      accurately reach target locations previously unachievable with conventional rigid
      needles. These active needles combined with an asymmetric bevel-tip can further
      improve their steerability. To optimize the design and to develop accurate path
      planning and control algorithms, there is a need to develop a tissue-needle
      interaction model. This work presents an energy-based model that predicts needle
      deflection of active bevel-tipped needles when inserted into the tissue. This
      current model was based on an existing energy-based model for bevel-tipped
      needles, to which work of actuation was included in calculating the system
      energy. The developed model was validated with needle insertion experiments with
      a phantom material. The model predicts needle deflection reasonably for higher
      diameter needles (11.6% error), whereas largest error was observed for the
      smallest needle diameter (24.7% error). 

PMID- 24296106
TI  - Crystalline silica in heated man-made vitreous fibres: a review.
AB  - Refractory ceramic fibres (RCF) and alkaline earth silicate (AES) wools are types
      of man-made vitreous fibre (MMVF) that are used in demanding high-temperature
      industrial applications, generally above 900  degrees C and up to 1400  degrees
      C. When exposed to prolonged high temperatures, MMVF can devitrify with the
      formation of cristobalite and other crystalline silica species, which is of
      potential concern because crystalline silica (CS) is classified as carcinogenic.
      This article reviews the chemico-physical processes and morphological
      consequences of fibre devitrification, the forms and micro-location of CS
      produced, and the toxicity of devitrified fibres and the CS species formed in
      this way. It also examines scenarios for worker exposure to the products of fibre
      devitrification in industries using RCF and/or AES wools. We identify gaps in
      knowledge and make recommendations for future research.

PMID- 24296107
TI  - Corrective effects of acerola (Malpighia emarginata DC.) juice intake on
      biochemical and genotoxical parameters in mice fed on a high-fat diet.
AB  - Acerola contains high levels of vitamin C and rutin and shows the corresponding
      antioxidant properties. Oxidative stress on the other hand is an important factor
      in the development of obesity. In this study, we investigated the biochemical and
      antigenotoxic effects of acerola juice in different stages of maturity (unripe,
      ripe and industrial) and its main pharmacologically active components vitamin C
      and rutin, when given as food supplements to obese mice. Initial HPLC analyses
      confirmed that all types of acerola juice contained high levels of vitamin C and
      rutin. DPPH tests quantified the antioxidant properties of these juices and
      revealed higher antioxidant potentials compared to pure vitamin C and rutin. In
      an animal test series, groups of male mice were fed on a standard (STA) or a
      cafeteria (CAF) diet for 13 weeks. The latter consisted of a variety of
      supermarket products, rich in sugar and fat. This CAF diet increased the feed
      efficiency, but also induced glucose intolerance and DNA damage, which was
      established by comet assays and micronucleus tests. Subsequently, CAF mice were
      given additional diet supplements (acerola juice, vitamin C or rutin) for one
      month and the effects on bone marrow, peripheral blood, liver, kidney, and brain
      were examined. The results indicated that food supplementation with ripe or
      industrial acerola juice led to a partial reversal of the diet-induced DNA damage
      in the blood, kidney, liver and bone marrow. For unripe acerola juice food
      supplementation, beneficial effects were observed in blood, kidney and bone
      marrow. Food supplementation with vitamin C led to decreased DNA damage in kidney
      and liver, whereas rutin supplementation led to decreased DNA damage in all
      tissue samples observed. These results suggest that acerola juice helps to reduce
      oxidative stress and may decrease genotoxicity under obesogenic conditions. 

PMID- 24296108
TI  - Emerging treatment strategies in recurrent platinum-sensitive ovarian cancer:
      focus on trabectedin.
AB  - Ovarian cancer (OC) is the leading cause of death from gynecological
      malignancies. In spite of high response rates to the standard front-line
      treatment for advanced disease with cytoreductive surgical debulking, followed by
      platinum/taxane-based chemotherapy, most patients eventually relapse developing
      drug-resistant disease. Owing to the molecular heterogeneity, genetic instability
      and mutagenicity of OC, increases in survival might be achieved by translating
      recent insights at the morpho-molecular levels to individual therapeutic
      strategies. Several emerging treatments have been shown to be active in platinum
      sensitive (PS) recurrent OC (ROC), but an optimal strategy still has not been
      established. Based on the recent results, it is likely that the introduction of
      novel non-platinum based chemotherapies and molecular targeted therapies will
      have a major impact on the management of ROC. Some current strategies are focused
      on the extension of platinum-free interval (PFI) in patients with PS,
      particularly in those with partially PS disease. Apparently, the PFI extension by
      an effective non-platinum intervention, such as trabectedin plus pegylated
      liposomal doxorubicin (PLD), may reduce cumulative platinum-induced toxicities
      leading to longer survival after the reintroduction of subsequent platinum. The
      introduction of novel therapies, such as the antiangiogenic monoclonal antibody
      bevacizumab, opens a new field of targeted therapies in this indication. In this
      review, we aim to outline the therapeutic potential of new emerging approaches,
      particularly the role of non-platinum therapy with trabectedin in combination
      with PLD in patients with PS ROC. 

PMID- 24296109
TI  - A systematic review of non-surgical treatments for pancreatic neuroendocrine
      tumours.
AB  - INTRODUCTION: Pancreatic neuroendocrine tumours (pNETs) are rare and the majority
      of patients present with advanced disease. Such patients have limited treatment
      options. We conducted a systematic review of published clinical trials of non
      surgical interventions in pNET, to understand the efficacy, safety and health
      related quality of life (HRQoL) outcomes from the current evidence base. METHODS:
      Electronic databases and manual bibliographic searches were conducted to identify
      relevant studies. Data were extracted by two independent reviewers. RESULTS:
      Forty seven clinical studies met the predefined inclusion criteria. The following
      interventions were included: targeted therapies (two RCTs and six single-arm
      studies), chemotherapy (two RCTs, one prospective nonrandomised, comparative
      study and 14 single-arm studies);somatostatin analogues (SSA) and radiolabeled
      SSA therapies (nine single-arm studies), liver-directed therapies (six single-arm
      studies), mixed treatment regimens (one RCT, four single-arm studies) and other
      interventions such as interferon and recombinant human endostatin (one single-arm
      study for each). The paucity of RCT data and lack of consistency in reporting
      validated study outcomes and differing patient inclusion criteria between studies
      made it difficult to compare the relative efficacy of therapies. DISCUSSION: The
      majority of published studies assessing treatment regimens for the management of
      pNET are single arm, non-randomised studies, often enrolling a small number of
      patients and not reporting clinically meaningful outcomes. However data from
      recently conducted studies assessing targeted therapies indicate that it is
      possible to conduct adequately powered RCTs reporting standardised oncological
      endpoints in this rare cancer. Further, similarly robust studies should be
      conducted to define the optimal treatment algorithm.

PMID- 24296110
TI  - Clock drawing as a screen for impaired driving in aging and dementia: is it worth
      the time?
AB  - Clock drawing is recommended by medical and transportation authorities as a
      screening test for unsafe drivers. The objective of the present study was to
      assess the usefulness of different clock drawing systems as screening measures of
      driving performance in 122 healthy and cognitively impaired older drivers. Clock
      drawing was measured using four different scoring systems. Driving outcomes
      included global ratings of safety and the error rate on a standardized on-road
      test. Findings revealed that clock drawing was significantly correlated with the
      driving score on the road test for each of the scoring systems. However, receiver
      operator curve analyses showed limited clinical utility for clock drawing as a
      screening instrument for impaired on-road driving performance with the area under
      the curve ranging from 0.53 to 0.61. Results from this study indicate that clock
      drawing has limited utility as a solitary screening measure of on-road driving,
      even when considering a variety of scoring approaches. 

PMID- 24296111
TI  - Lysine acetylsalicylate increases the safety of a paraquat formulation to
      freshwater primary producers: a case study with the microalga Chlorella vulgaris.
AB  - Large amounts of herbicides are presently used in the industrialized nations
      worldwide, with an inexorable burden to the environment, especially to aquatic
      ecosystems. Primary producers such as microalgae are of especial concern because
      they are vital for the input of energy into the ecosystem and for the maintenance
      of oxygen in water on which most of other marine life forms depend on. The
      herbicide paraquat (PQ) is known to cause inhibition of photosynthesis and
      irreversible damage to photosynthetic organisms through generation of reactive
      oxygen species in a light-dependent manner. Previous studies have led to the
      development of a new formulation of PQ containing lysine acetylsalicylate (LAS)
      as an antidote, which was shown to prevent the mammalian toxicity of PQ, while
      maintaining the herbicidal effect. However, the safety of this formulation to
      primary producers in relation to commercially available PQ formulations has
      hitherto not been established. Therefore, the aim of this study was to evaluate
      the toxicity of the PQ+LAS formulation in comparison with the PQ, using Chlorella
      vulgaris as a test organism. Effect criterion was the inhibition of microalgal
      population growth. Following a 96 h exposure to increasing concentrations of PQ,
      C. vulgaris growth was almost completely inhibited, an effect that was
      significantly prevented by LAS at the proportion used in the formulation (PQ+LAS)
      1:2 (mol/mol), while the highest protection was achieved at the proportion of
      1:8. In conclusion, the present work demonstrated that the new formulation with
      PQ+LAS has a reduced toxicity to C. vulgaris when compared to Gramoxone((r)).

PMID- 24296112
TI  - Contrasting effects of nitrogenous pollution on fitness and swimming performance
      of Iberian waterfrog, Pelophylax perezi (Seoane, 1885), larvae in mesocosms and
      field enclosures.
AB  - Amphibians are declining worldwide and pollutants have been implicated as a major
      contributor to these declines. To understand these declines, many studies have
      assessed the impact of pollutants on amphibian behaviour. However, information
      regarding their effect on locomotor abilities, as well as the intra-specific
      variation of the tolerance to pollutants, is extremely rare. Further, the
      majority of studies examining the impact of pollutants on amphibians have been
      conducted in simplified laboratory settings. Given the complexity of natural
      systems, determining whether amphibian responses in laboratory studies can be
      generalized to more realistic natural scenarios is critical. Towards this goal,
      this study assessed the impact of nitrogenous pollution on survival and fitness
      related larval traits (growth, mass and swimming performance) for three
      populations of the frog Pelophylax perezi, exposed to different degrees of
      eutrophication in two different and complementary experiments: (1) pond
      mesocosms, with NH4Cl isolated or combined with NaNO2 and NaNO3, and (2) field
      enclosures placed in natural streams differing in their degree of pollution. For
      both mesocosm and field enclosure experiments, larval mortality was unaffected by
      nitrogenous pollution. However, in the mesocosm experiment, exposure to
      nitrogenous compounds reduced final larvae mass and growth. In contrast, in the
      enclosure experiment, polluted locations facilitated final mass and growth of
      surviving tadpoles. Population-level variation in the effect of pollution was
      observed for final larval mass in the mesocosm but not in the field enclosure
      experiment. In addition, although nitrogenous compounds in both mesocosm and
      natural conditions had no direct effect on absolute larval swimming performance,
      they may impact the viability of larvae by affecting the relationships between
      growth and the swimming abilities. The differential pattern found in the impacts
      of nitrogenous compounds on larvae of P. perezi when raised in different
      experimental venues (mesocosms and field conditions) points to the convenience of
      considering more realistic natural scenarios in assessing the impact of
      pollutants on amphibians. 

PMID- 24296113
TI  - Comment on: Effects of laparoscopic sleeve gastrectomy on attentional processing
      of food-related information: evidence from eye-tracking.

PMID- 24296114
TI  - Alcohol stress on cardiac tissue - ameliorative effects of Thespesia populnea
      leaf extract.
AB  - BACKGROUND: Cells are naturally equipped with antioxidant defenses to
      counterbalance free radical production. Overproduction of free radicals is one of
      the reasons for a variety of diseases. The current investigation was planned to
      evaluate chronic alcohol- (for 30 days) induced oxidative stress in the cardiac
      tissue of rat and to explore the effectiveness of Thespesia populnea (TP)-induced
      cardio-protection in rat heart by utilizing an in vivo model of cardiac injury by
      alcohol. METHODS: Ten groups of rats were maintained and were divided into
      different groups. Alcohol 20% was administered and Thespesia leaf extracts (TPE)
      were administered at a dose of 250 mg/kg to chronic alcoholic rats for 30 days.
      The heart tissue was isolated and processed for further analysis, and also blood
      for estimation of blood alcohol level and serum creatine phosphokinase (CPK). The
      activities/levels of antioxidant enzymes, malondialdehyde (MDA), and protein
      carbonyls (PC) were estimated using established protocols. Histopathology was
      performed as evidence for the work and to establish the results. RESULTS:
      Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced
      glutathione content (GSH) showed a decrease, while glutathione-S-transferase
      (GST) activity, MDA, and PC recorded an elevation due to alcohol treatment in the
      cardiac tissue compared to the control rats. Alcohol-induced myocardial injury
      was observed, indicated by a significant increase in serum CPK, a well-known
      biomarker of myocardial injury, and histopathological evidence supported these
      observations by revealing predominantly extensive edema with vacuolization and
      severe necrosis. CONCLUSION: Treatment with TPE confers protection on the heart
      tissue during alcohol-induced oxidative stress, and thereby minimizes oxidative
      damage to the cardiac tissue as clearly marked in histopathology.

PMID- 24296115
TI  - Role of multiligand/RAGE axis in platelet activation.
AB  - In the context of plaque progression, platelet hyperactivity associated with
      hyperlipidemia contributes to the development of a pro-thrombotic state. In this
      context, it has been demonstrated that advanced glycation end products (AGEs)
      significantly increases platelet activation and receptor for AGEs (RAGE)
      expression at the platelet surface membrane. In addition to AGEs, other ligands
      (S100, HMGB1 and amyloid beta, among others) of RAGE have raised particular
      attention in platelet activation. Therefore, in this article we describe platelet
      hyperactivity by AGEs via RAGE-independent and RAGE-dependent pathways. 

PMID- 24296116
TI  - An approach for automated fault diagnosis based on a fuzzy decision tree and
      boundary analysis of a reconstructed phase space.
AB  - Although reconstructed phase space is one of the most powerful methods for
      analyzing a time series, it can fail in fault diagnosis of an induction motor
      when the appropriate pre-processing is not performed. Therefore, boundary
      analysis based a new feature extraction method in phase space is proposed for
      diagnosis of induction motor faults. The proposed approach requires the
      measurement of one phase current signal to construct the phase space
      representation. Each phase space is converted into an image, and the boundary of
      each image is extracted by a boundary detection algorithm. A fuzzy decision tree
      has been designed to detect broken rotor bars and broken connector faults. The
      results indicate that the proposed approach has a higher recognition rate than
      other methods on the same dataset. 

PMID- 24296117
TI  - Intraosseous dentinogenic ghost cell tumor: a clinical report and literature
      update.
AB  - The dentinogenic ghost cell tumor (DGCT) is a relatively uncommon locally
      invasive neoplasm. This report describes the case of a 20-year-old Caucasian
      female patient who was diagnosed with an intraosseous DGCT in the left molar
      region of the mandible. Radiographic analysis revealed a well-circumscribed
      radiolucent lesion with focal radiopacity. Segmental resection of the mandible
      was performed by means of piezoelectric surgery. The histopathological
      examination yielded islands of odontogenic epithelium with clusters of ghost
      cells and dysplastic dentin, thus enabling the identification of the lesion as
      DGCT. Long-term surveillance of patients with intraosseous DGCTs is mandatory in
      order to detect in time any signs of recurrence. A literature update concerning
      intraosseous DGCTs is also provided. 

PMID- 24296118
TI  - Local and systemic risk factors influencing the long-term success of angular
      stable alloplastic reconstruction plates of the mandible.
AB  - INTRODUCTION: After ablative surgery of the mandible, angular stable alloplastic
      reconstruction plates are commonly employed. The aim of the study was a long-term
      evaluation of local anatomical, as looking at systemic factors influencing
      specific complications and the failure rate of such plates. MATERIALS AND
      METHODS: In a retrospective study covering an 11-year period, we reviewed the
      outcomes of angular stable plates of patients who had a segmental resection of
      the mandible and subsequent alloplastic reconstruction. Complications and failure
      rates were assessed and local (anatomical size and localization of resection) as
      well as systemic risk factors (age, sex, radiation therapy, smoking) evaluated.
      RESULTS: Altogether, 162 plates were reviewed. The overall complication rate was
      28% (fractures n = 8, loose screws n = 7, dehiscences n = 31) after an average
      time of 13 months. Cumulative survival rates of 73% after one, of 67% after 2, of
      59% after 3 and of 40% after five years were observed. We found a significant
      correlation of increasing defect sizes to a rising complication and failure rate.
      Plate dehiscence occurred more often in defects including the midline (p =
      0.005). Though not statistically significant, the occurrence of plate fracture
      was associated with lateral mandibular defects (7/8, p = 0.113). In smoking
      patients an earlier failure rate was seen. CONCLUSION: The results clearly
      indicate that the success of alloplastic reconstruction plates of the mandible is
      dependent on various risk factors. They should--if possible--be used temporarily
      only. If not done primarily, a secondary approach with bone reconstruction is
      recommended.

PMID- 24296119
TI  - Comparison of compressive strength between three different plates for mandibular
      angle fractures fixation.
AB  - The present study aims to compare three types of internal fixation for fractures
      of the mandibular angle. Mechanical testing was performed on replicas of
      polyurethane hemimandibles sectioned at the angle region to simulate a fracture
      and fixed with three different hardwares. Fixation devices enrolled on this
      survey included the grid plates with and without an intermediate bar and the
      method described by Champy and colleagues in 1978 and the sample consisted of 10
      hemimandibles for each group. Vertical loadings were applied on each hemimandible
      and recorded after a vertical displacement of 3 and 5 mm. Statistical analysis
      was made by means of the variance analysis (ANOVA) and the Duncan test with a
      significance level of 5%. The Champy technique showed a statistically significant
      increased resistance when compared to the grid plates after vertical
      displacements of 3 and 5 mm. The results of this survey suggest that the Champy
      technique, when compared to the grid plate positioned at the middle of the
      mandibular bone (placement site selected for this study), is more resistant than
      the grid plate and that the inclusion or not of an intermediate bar to the grid
      plates does not improve its resistance after linear vertical loadings. 

PMID- 24296120
TI  - Development of lipid productivities under different CO2 conditions of marine
      microalgae Chlamydomonas sp. JSC4.
AB  - Biodiesel production from microalgae has become a popular research topic. In this
      study, Chlamydomonas sp. JSC4 isolated from the southern coast of Taiwan was
      selected for a detailed study on cell growth and lipid accumulation under marine
      salinity (3.5% sea salt). Proper CO2 was supplied as the improvement of lipid
      productivity. Under the optimal condition, the highest lipid productivity was
      169.1mg/L/d, which was significantly higher than those reported in current
      studies for marine green algae. To date, only very few studies have reported a
      marine algae strain with both high cell growth and lipid productivity. This study
      demonstrated that a newly isolated marine green alga Chlamydomonas sp. JSC4 would
      be a feasible oil producer due to its high biomass production and lipid
      productivity under marine salinity. 

PMID- 24296121
TI  - An improved TCF sequence for biobleaching kenaf pulp: influence of the
      hexenuronic acid content and the use of xylanase.
AB  - Enzymatic delignification with laccase from Trametes villosa used in combination
      with chemical mediators (acetosyringone, acetovanillone and 1
      hydroxybenzotriazole) to improve the totally chlorine-free (TCF) bleaching of
      kenaf pulp was studied. The best final pulp properties were obtained by using an
      LHBTQPo sequence developed by incorporating a laccase-mediator stage into an
      industrial bleaching sequence involving chelation and peroxide stages. The new
      sequence resulted in increased kenaf pulp delignification (90.4%) and brightness
      (77.2%ISO) relative to a conventional TCF chemical sequence (74.5%
      delignification and 74.5% brightness). Also, the sequence provided bleached kenaf
      fibers with high cellulose content (pulp viscosity of 890 g.mL(-1) vs 660 g.mL(
      1)). Scanning electron micrographs revealed that xylanase altered fiber surfaces
      and facilitated reagent access as a result. However, the LHBTX (xylanase) stage
      removed 21% of hexenuronic acids in kenaf pulp. These recalcitrant compounds
      spent additional bleaching reagents and affected pulp properties after peroxide
      stage.

PMID- 24296122
TI  - Enhancing lutein productivity of an indigenous microalga Scenedesmus obliquus FSP
      3 using light-related strategies.
AB  - Lutein, one of the main photosynthetic pigments, is a promising natural product
      with both nutritional and pharmaceutical applications. In this study, light
      related strategies were applied to enhance the cell growth and lutein production
      of a lutein-rich microalga Scenedesmus obliquus FSP-3. The results demonstrate
      that using white LED resulted in better lutein production efficiency when
      compared to the other three monochromatic LEDs (red, blue, and green). The lutein
      productivity of S. obliquus FSP-3 was further improved by adjusting the type of
      light source and light intensity. The optimal lutein productivity of 4.08 mg/L/d
      was obtained when using a TL5 fluorescent lamp at a light intensity of 300
      MUmol/m(2)/s, and this performance is better than that reported in most related
      studies. Moreover, the time-course profile of lutein accumulation in the
      microalga shows that the maximal lutein content and productivity were obtained at
      the onset of nitrogen depletion.

PMID- 24296123
TI  - pH-upshock yields more lipids in nitrogen-starved Neochloris oleoabundans.
AB  - This study explores the influence of alkaline pH and light intensity on the
      performance of Neochloris oleoabundans in two-stage batch cultivation: a first
      stage for nitrogen-sufficient growth followed by a second stage for lipid
      accumulation under nitrogen starvation. The highest TAG yield on absorbed light
      was obtained at low light conditions when pre-cultivation occurred at pH 8 and
      lipid accumulation was induced at pH 10. However, a higher alkaline pH by itself
      appears not to enhance the starvation-induced increase in lipid contents, except
      when combined with high light and pre-cultivation occurs at those same
      conditions. Such strategy however also results in low biomass and TAG yields on
      absorbed light. Fatty acid composition analysis revealed that the relative fatty
      acid contents of the TAG pool are nevertheless independent from the light
      intensity and pH applied at either cultivation stage, suggesting a high
      specificity of N. oleoabundans cell machinery towards TAG production. 

PMID- 24296125
TI  - Imaging the developing brain.

PMID- 24296124
TI  - Clinicopathological characteristics and surgical results of lung cancer patients
      aged up to 50 years: the Japanese Lung Cancer Registry Study 2004.
AB  - OBJECTIVE: The clinicopathological characteristics and surgical results of young
      lung cancer patients were investigated. MATERIALS AND METHODS: Seven hundred and
      four (6.0%) patients with lung cancer, aged up to 50 years, were enrolled from
      among the 11,663 patients registered in the Japanese Lung Cancer Registry Study
      2004, and their clinical data were compared with those of 10,959 patients older
      than 50 years. This epidemiological study is based on the single year
      registration of surgically treated patients in the major institutes in Japan.
      RESULTS: The 5-year overall survival rate (5Y-OS) and the 5-year lung cancer
      related survival rate was 79.2%/69.0% (p<0.001) and 81.3%/76.6% (p=0.005) in the
      young/old groups, respectively. In the young/old groups, lobectomy and
      pneumonectomy was performed in 76.9%/78.0% and 5.7%/3.2%, respectively; adjuvant
      therapies were given preoperatively in 10.4%/4.7% (p<0.001) and postoperatively
      in 31.4%/24.5% (p<0.001). The proportions of patients with p-stage IIIA (18.2%)
      and adenocarcinoma histology (78.7%) were higher in the young group. The 5Y-OS
      was 94.8%/86.2% for p-stage IA (p<0.001), 87.0%/73.2% for p-stage IB (p=0.001),
      61.0%/61.6% for p-stage IIA (p=0.595), 71.0%/48.4% for p-stage IIB (p=0.003),
      49.6%/39.4% for p-stage IIIA (p=0.020), and 80.0%/24.8% for p-stage IIIB
      (p=0.012); it was 83.5%/80.7% for females (p=0.106) and 75.1%/62.3% for males
      (p<0.001) in the young/old groups. The postoperative survival was significantly
      better with all operative procedures in the young group. The 5Y-OS after
      recurrence was 17.9%/13.4% in the young/old groups (p=0.016). In the young group,
      the 5Y-OS was better in females (83.5%) than in males (75.1%, p=0.002), and for
      patients with adenocarcinoma (80.3%) than for those with squamous cell carcinoma
      (68.5%, p=0.013). Age up to 50 years was identified as an independent better
      prognostic factor on multivariate analysis. CONCLUSIONS: The postoperative
      survival in lung cancer patients aged up to 50 years was better than that in
      patients older than 50 years.

PMID- 24296126
TI  - The adipogenic potential of various extracellular matrices under the influence of
      an angiogenic growth factor combination in a mouse tissue engineering chamber.
AB  - The extracellular matrix (ECM) MatrigelTM has frequently and successfully been
      used to generate new adipose tissue experimentally, but is unsuitable for human
      application. This study sought to compare the adipogenic potential of a number of
      alternative, biologically derived or synthetic ECMs with potential for human
      application, with and without growth factors and a small fat autograft. Eight
      groups, with six severe combined immunodeficient (SCID) mice per group, were
      created with bilateral chambers (silicone tubes) implanted around the epigastric
      vascular pedicle, with one chamber/animal containing a 5mg fat autograft. Two
      animal groups were created for each of four ECMs (MatrigelTM, Myogel, Cymetra(r)
      and PuraMatrixTM) which filled the bilateral chambers. One group/ECM had no
      growth factors added to chambers whilst the other group had growth factors (GFs)
      (vascular endothelial growth factor-A (VEGF-A) plus fibroblast growth factor-2
      (FGF-2) plus platelet-derived growth factor-BB (PDGF-BB)) added to both chambers.
      At 6weeks, chamber tissue was morphometrically assessed for percent and absolute
      adipose tissue volume. Overall, the triple GF regime significantly increased
      percent(*) and absolute(#) adipose tissue volume (p<0.0005(*#)) compared to
      chambers without triple GF treatment. The fat autograft also significantly
      increased percent (p<0.0005) and absolute (p<0.011) adipose tissue volume.
      Cymetra(r) (human collagen) constructs yielded the largest total tissue and
      absolute adipose tissue volume. We found that the pro-angiogenic FGF-2, VEGF-A
      and PDGF-BB combination in ECMs of synthetic and biological origin produced an
      overall significantly increased adipose tissue volume at 6weeks and may have
      clinical application, particularly with Cymetra. 

PMID- 24296127
TI  - Magnesium in the murine artery: probing the products of corrosion.
AB  - Many publications are available on the physiological and pseudophysiological
      corrosion of magnesium and its alloys for bioabsorbable implant application, yet
      few focus on the characterization of explanted materials. In this work,
      commercially pure magnesium wires were corroded in the arteries of rats for up to
      1 month, removed, and both bulk and surface products characterized. Surface
      characterization using infrared spectroscopy revealed a duplex structure
      comprising heavily magnesium-substituted hydroxyapatite that later transformed
      into an A-type (carbonate-substituted) hydroxyapatite. To explain this
      transformation, an ion-exchange mechanism is suggested. Elemental mapping of the
      bulk products of biocorrosion revealed the elemental distribution of Ca, P, Mg
      and O in the outer and Mg, O and P in the inner layers. Carbon was not observed
      in any significant quantity from the inner corrosion layer, suggesting that
      carbonates are not a prevalent product of corrosion. Backscatter electron imaging
      of cross-sections showed that thinning or absence of the hydroxyapatite in the
      later stages of degradation is related to local thickening of the inner corrosion
      layer. Based on these experimental observations, mechanisms describing corrosion
      in the quasi-steady state and during terminal breakdown of the magnesium
      specimens are proposed.

PMID- 24296128
TI  - Association of oxidative DNA damage, protein oxidation and antioxidant function
      with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers
      during fetal circulation.
AB  - Pre-eclampsia is a devastating multi system syndrome and a major cause of
      maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated
      with oxidative stress in the maternal circulation. To have an insight on the
      effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore
      the oxidative status by quantification of byproducts generated during protein
      oxidation and oxidative DNA damage and deficient antioxidant activity in
      umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation.
      Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic
      mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated
      pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine),
      protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E,
      C), total antioxidant status and iron status were determined. Significant
      elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with
      decreased levels of catalase, vitamin A, E, C, total antioxidant status were
      observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies.
      These parameters might be influential variables for the risk of free radical
      damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased
      oxidative stress causes oxidation of DNA and protein which alters antioxidant
      function. Excess iron level and decreased unsaturated iron binding capacity may
      be the important factor associated with oxidative stress and contribute in the
      pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation. 

PMID- 24296129
TI  - Sulforaphane induces reactive oxygen species-mediated mitotic arrest and
      subsequent apoptosis in human bladder cancer 5637 cells.
AB  - The present study was undertaken to determine whether sulforaphane-derived
      reactive oxygen species (ROS) might cause growth arrest and apoptosis in human
      bladder cancer 5637 cells. Our results show that the reduced viability of 5637
      cells by sulforaphane is due to mitotic arrest, but not the G2 phase. The
      sulforaphane-induced mitotic arrest correlated with an induction of cyclin B1 and
      phosphorylation of Cdk1, as well as a concomitant increased complex between
      cyclin B1 and Cdk1. Sulforaphane-induced apoptosis was associated with the
      activation of caspase-8 and -9, the initiators caspases of the extrinsic and
      intrinsic apoptotic pathways, respectively, and activation of effector caspase-3
      and cleavage of poly (ADP-ribose) polymerase. However, blockage of caspase
      activation inhibited apoptosis and abrogated growth inhibition in sulforaphane
      treated 5637 cells. This study further investigated the roles of ROS with respect
      to mitotic arrest and the apoptotic effect of sulforaphane, and the maximum level
      of ROS accumulation was observed 3h after sulforaphane treatment. However, a ROS
      scavenger, N-acetyl-L-cysteine, notably attenuated sulforaphane-mediated
      apoptosis as well as mitotic arrest. Overall, these results suggest that
      sulforaphane induces mitotic arrest and apoptosis of 5637 cells via a ROS
      dependent pathway. 

PMID- 24296130
TI  - Genipin induces cyclooxygenase-2 expression via NADPH oxidase, MAPKs, AP-1, and
      NF-kappaB in RAW 264.7 cells.
AB  - Genipin is a compound found in gardenia fruit extract with diverse
      pharmacological activities. However, the mechanism underlying genipin-induced
      cyclooxygenase-2 (COX-2) expression remains unknown. In this study, we
      investigated the effects of genipin on COX-2 expression and determined that
      exposure to genipin dose-dependently enhanced the production of prostaglandin E2
      (PGE2), a major COX-2 metabolite, in RAW 264.7 cells. These effects were mediated
      by genipin-induced activation of the COX-2 promoter, as well as AP-1 and NF
      kappaB luciferase constructs. Phosphatidylinositol-3-kinase/Akt and MAPKs were
      also significantly activated by genipin, and Akt and MAPKs inhibitors (PD98059,
      SB20358, SP600125, and LY294002) inhibited genipin-induced COX-2 expression.
      Moreover, genipin increased production of the ROS and the ROS-producing NAPDH
      oxidase (NOX) family oxidases, NOX2 and NOX3. Inhibition of NADPH with
      diphenyleneiodonium attenuated ROS production, COX-2 expression and NF-kappaB and
      AP-1 activation. These results suggest that the molecular mechanism mediating ROS
      dependent COX-2 up-regulation and PGE2 production by genipin involves activation
      of Akt, MAPKs and AP-1/NF-kappaB. 

PMID- 24296131
TI  - Effects of allantoin on cognitive function and hippocampal neurogenesis.
AB  - Allantoin is contained in Nelumbo nucifera (lotus) and a well-known cosmetic
      ingredient reported to have anti-oxidative and anti-inflammatory activities. In
      the present study, we investigated whether allantoin affects cognitive function
      in mice. The subchronic administration of allantoin (1, 3 or 10 mg/kg, for 7
      days) significantly increased the latency time measured during the passive
      avoidance task in scopolamine-induced cholinergic blockade and normal naive mice.
      Allantoin treatment (3 or 10 mg/kg, for 7 days) also increased the expression
      levels of phosphorylated phosphatidylinositide 3-kinase (PI3K), phosphorylated
      protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3beta (GSK
      3beta). Doublecortin and 5-bromo-2-deoxyuridine immunostaining revealed that
      allantoin significantly increased the neuronal cell proliferation of immature
      neurons in the hippocampal dentate gyrus region. In conclusion, allantoin has
      memory-enhancing effects, and these effects may be partly mediated by the PI3K
      Akt-GSK-3beta signal pathway. These findings suggest that allantoin has
      therapeutic potential for the cognitive dysfunctions observed in Alzheimer's
      disease.

PMID- 24296132
TI  - Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and
      kidney following subchronic exposure.
AB  - Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to
      its bio-accumulative property. Isolated studies of TBT toxicity on different
      organs are available but consolidated information is greatly lacking. We planned
      this study to delineate the effect of subchronic (1 month) exposure to low dose
      TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration
      was found to be significantly increased in liver, kidney and blood, and
      marginally in lungs. Organo-somatic indices were seen to be altered with little
      effect on serum biochemical markers (liver and kidney function, and general
      parameters). Reactive oxygen species but not lipid peroxidation content was
      observed to be significantly elevated both in the tissues and serum. TBTC was
      found to act as a hyperlipidemic agent and it also affected heme biosynthetic
      pathway. Hematological analysis showed that TBTC exposure resulted in minor
      alterations in RBC parameters. Histological studies demonstrated marked tissue
      damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants
      (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex
      vivo conditions. Antioxidants were evidently more efficient in comparison to the
      calcium inhibitors, implying major role of oxidative stress pathways in TBTC
      toxicity.

PMID- 24296133
TI  - Speciated arsenic concentrations, exposure, and associated health risks for rice
      and bulgur.
AB  - Arsenic species were determined in rice and bulgur samples that were collected
      from 50 participants who also supplied exposure related information through a
      questionnaire survey. Speciation analysis was conducted using an HPLC-ICP-MS
      system. Ingestion exposure to arsenic and associated health risks were assessed
      by combining the concentration and questionnaire data both for individual
      participants and the subject population. Inorganic arsenic dominated both in rice
      and bulgur but concentrations were about an order of magnitude higher in rice
      (160+/-38 ng/g) than in bulgur. Because participants also consumed more rice than
      bulgur, exposures were significantly higher for rice resulting in carcinogenic
      risks above acceptable level for 53% and 93% of the participants when the in
      effect and the proposed potencies were used, respectively, compared to 0% and 5%
      for bulgur. An inorganic arsenic standard for rice would be useful to lower the
      risks while public awareness about the relation between excessive rice
      consumption and health risks is built, and bulgur consumption is promoted.

PMID- 24296134
TI  - Plumbagin inhibits LPS-induced inflammation through the inactivation of the
      nuclear factor-kappa B and mitogen activated protein kinase signaling pathways in
      RAW 264.7 cells.
AB  - Plumbagin (PL) has been reported to exhibit anti-carcinogenic, anti-inflammatory
      and analgesic activities, but little is known about its mechanism. In this study,
      we investigated the anti-inflammatory property of PL and its mechanism of action.
      Although no significant cytotoxicity of PL was observed over the concentration
      range tested, PL (2.5-7.5 MUM) significantly and dose-dependently suppressed the
      secretion of pro-inflammatory mediators and inhibited the expression of TNF
      alpha, IL-1beta, IL-6 and iNOS in LPS-stimulated RAW 264.7 cells. Furthermore, PL
      consistently suppressed the activity of iNOS in LPS-induced RAW 264.7 cells. To
      elucidate the mechanism underlying the anti-inflammatory activity of PL, we
      assessed the effects of PL on the MAPK pathway and the activity and expression of
      NF-kappaB. These experiments demonstrated that PL significantly reduced the
      luciferase activity of an NF-kappaB promoter reporter and p65 nuclear
      translocation. The LPS-induced phosphorylation of MAP kinases was also attenuated
      by PL; significant changes were observed in the levels of phosphorylated ERK1/2,
      JNK and p38 MAPK. Additionally, MAPK inhibitors confirmed the inhibitory effect
      of PL on the MAPK pathway. Taken together, these data suggest that PL exerts its
      anti-inflammatory effects by down-regulating the expression of pro-inflammatory
      mediators through inhibition of NF-kappaB and MAPK signaling in LPS-stimulated
      RAW 264.7 cells.

PMID- 24296135
TI  - Naringin accelerates the regression of pre-neoplastic lesions and the colorectal
      structural reorganization in a murine model of chemical carcinogenesis.
AB  - The aim of this study was to investigate the effect of Naringin on pre-neoplastic
      colorectal lesions induced by chemical carcinogen in rats. Female Wistar rats
      weighing 130.8+/-27.1 g received weekly one subcutaneous injection of 1,2
      dimethylhydrazine (DMH, 20 mg/kg) for 10 weeks. The animals were divided into 5
      groups with 6 animals in each group. Group 1: 0.9% saline; Group 2: DMH+0.9%
      saline; Group 3: DMH+Naringin (10 mg/kg); Group 4: DMH+Naringin (100 mg/kg);
      Group 5: DMH+Naringin (200 mg/kg). G2 and G3 showed a significant increase in ACF
      number, AgNOR/nucleus and mitosis compared to G1. G4 and G5 presented a
      significant reduction in these parameters compared to G2. The number of cells
      producing acidic and neutral mucins, red blood cells and the level of antioxidant
      minerals, such as copper, magnesium, selenium and zinc, were significantly
      reduced in G2 and G3, but similar in G4 and G5 compared to G1. Naringin,
      especially at 200 mg/kg, was effective in reducing the number of pre-neoplastic
      lesions in rats exposed to DMH. Some of these effects may be due to reduction in
      cellular proliferation and tissue levels of iron together with the recovery of
      antioxidant mineral levels induced by this flavonoid.

PMID- 24296136
TI  - Fecal water genotoxicity in healthy free-living young Italian people.
AB  - Dietary habit affects the composition of human feces thus determining intestinal
      environment and exposure of colon mucosa to risk factors. Fecal water (FW)
      citotoxicity and genotoxicity were investigated in 33 healthy young Italian
      people, as well as the relationship between genotoxicity and nutrient intake or
      microflora composition. Two fecal samples were collected at 2 weeks apart and 3-d
      dietary diary was recorded for each volunteer. Cytotoxicity was measured using
      the Trypan Blue Dye Exclusion assay and genotoxicity using the Comet Assay
      (alkaline single-cell electrophoresis). Fecal bifidobacteria, total microbial
      count and nutrient intakes were also assessed. High intra- and inter-variability
      in genotoxicity data and in bacteria counts were found. None of the FW samples
      were citotoxic, but 90% of FW samples were genotoxic. Seventy five percent
      indicated intermediate and 15% were highly genotoxic. There was a different sex
      related distribution. Genotoxicity was positively correlated to the total lipid
      intake in females and to the bifidobacteria/total bacteria count ratio in male
      volunteers. These results demonstrate that the majority of FW samples isolated
      from free-living Italian people show intermediate level of genotoxicity and
      sustain a relation between this possible non-invasive marker of colorectal cancer
      risk with both dietary habits and colonic ecosystem.

PMID- 24296137
TI  - Seleno- and telluro-xylofuranosides attenuate Mn-induced toxicity in C. elegans
      via the DAF-16/FOXO pathway.
AB  - Organochalcogens are promising pharmacological agents that possess significant
      biological activities. Nevertheless, because of the complexity of mammalian
      models, it has been difficult to determine the molecular pathways and specific
      proteins that are modulated in response to treatments with these compounds. The
      nematode worm Caenorhabditis elegans is an alternative experimental model that
      affords easy genetic manipulations, green fluorescent protein tagging and in vivo
      live analysis of toxicity. Abundant evidence points to oxidative stress in
      mediating manganese (Mn)-induced toxicity. In this study we challenged worms with
      Mn, and investigated the efficacy of inedited selenium- and tellurium
      xylofuranosides in reversing and/or protecting the worms from Mn-induced
      toxicity. In addition, we investigated their putative mechanism of action. First,
      we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides
      on various toxic parameters. This was followed by studies on the ability of
      xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te
      xylofuranosides increased the expression of superoxide dismutase (SOD-3).
      Furthermore, we observed that the xylofuranosides induced nuclear translocation
      of the transcription factor DAF-16/FOXO, which in the worm is known to regulate
      stress responsiveness, aging and metabolism. These findings suggest that
      xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO
      signaling pathway. 

PMID- 24296138
TI  - Steviol glucuronidation and its potential interaction with UDP
      glucuronosyltransferase 2B7 substrates.
AB  - Hydrolysis of stevioside and rebaudioside A in the gastrointestinal tract after
      oral intake leads to the formation of steviol, the aglycone, which is absorbed
      into the circulation. Although in vivo studies have shown that steviol is cleared
      from the body via glucuronidation, the role of liver vs. intestine in steviol
      glucuronidation has not been well defined and related UDP
      glucuronosyltransferases (UGTs) have not been identified. The present study
      investigated steviol glucuronidation and obtained kinetic parameters in liver and
      intestinal microsomes of human and rat, as well as in recombinant human UGT
      systems. Results suggest that organ specificity exists in the intrinsic clearance
      of the glucuronidation reaction. Steviol glucuronidation was primarily mediated
      by UGT2B7 at low concentration and UGT2B7 and UGT1A3 at high concentration.
      Inhibition studies with selected UGT2B7 substrates indicate that diclofenac
      displayed a relatively strong inhibition (Ki, 4.2 MUM) against steviol
      glucuronidation in human liver microsomes. Taken together, the identification of
      the involvement of UGT2B7 in steviol glucuronidation would provide a mechanistic
      basis for the evaluation of the interaction between steviol and diclofenac. As
      metabolic clearance of botanical-derived products can be the objects (victims) of
      botanical-drug interactions, further studies are needed to investigate the in
      vivo relevance of such interactions.

PMID- 24296139
TI  - Exhaled breath condensate: determination of non-volatile compounds and their
      potential for clinical diagnosis and monitoring. A review.
AB  - Exhaled breath condensate is a promising, non-invasive, diagnostic sample
      obtained by condensation of exhaled breath. Starting from a historical
      perspective of early attempts of breath testing towards the contemporary state-of
      the-art breath analysis, this review article focuses mainly on the progress in
      determination of non-volatile compounds in exhaled breath condensate. The
      mechanisms by which the aerosols/droplets of non-volatile compounds are formed in
      the airways are discussed with methodological consequences for sampling. Dilution
      of respiratory droplets is a major problem for correct clinical interpretation of
      the measured data and there is an urgent need for standardization of EBC. This
      applies also for collection instrumentation and therefore various commercial and
      in-house built devices are described and compared with regard to their design,
      function and collection parameters. The analytical techniques and methods for
      determination of non-volatile compounds as potential markers of oxidative stress
      and lung inflammation are scrutinized with an emphasis on method suitability,
      sensitivity and appropriateness. The relevance of clinical findings for each
      group of possible non-volatile markers of selected pulmonary diseases and
      methodological recommendations with emphasis on interdisciplinary collaboration
      that is essential for future development into a fully validated clinical
      diagnostic tool are given. 

PMID- 24296140
TI  - Comparative study of the electrochemical behavior and analytical applications of
      (bio)sensing platforms based on the use of multi-walled carbon nanotubes
      dispersed in different polymers.
AB  - This review present a critical comparison of the electrochemical behavior and
      analytical performance of glassy carbon electrodes (GCE) modified with carbon
      nanotubes (CNTs) dispersed in different polymers: polyethylenimine (PEI), PEI
      functionalized with dopamine (PEI-Do), polyhistidine (Polyhis), polylysine
      (Polylys), glucose oxidase (GOx) and double stranded calf-thymus DNA (dsDNA). The
      comparison is focused on the analysis of the influence of the sonication time,
      solvent, polymer/CNT ratio, and nature of the polymer on the efficiency of the
      dispersions and on the electrochemical behavior of the resulting modified
      electrodes. The results allow to conclude that an adequate selection of the
      polymers makes possible not only an efficient dispersion of CNTs but also, and
      even more important, the building of successful analytical platforms for the
      detection of different bioanalytes like NADH, glucose, DNA and dopamine. 

PMID- 24296141
TI  - Discrimination and simultaneous determination of hydroquinone and catechol by
      tunable polymerization of imidazolium-based ionic liquid on multi-walled carbon
      nanotube surfaces.
AB  - Tunable polymerization of ionic liquid on the surfaces of multi-walled carbon
      nanotubes (MWCNTs) was achieved by a mild thermal-initiation-free radical
      reaction of 3-ethy-1-vinylimidazolium tetrafluoroborate in the presence of
      MWCNTs. Successful modification of polymeric ionic liquid (PIL) on MWCNTs
      surfaces (PIL-MWCNTs) was demonstrated by scanning electron microscopy,
      transmission electron microscopy, Fourier transform infrared spectroscopy,
      thermogravimetric analysis and X-ray photoelectron spectroscopy. The resulting
      PIL-MWCNTs possessed unique features of high dispersity in aqueous solution and
      tunable thickness of PIL layer, due to positive imidazole groups along PIL chains
      and controllable ionic liquid polymerization by tuning the ratio of precursor.
      Based on cation-pi interaction between the positive imidazole groups on PIL
      MWCNTs surface and hydroquinone (HQ) or catechol (CC), excellent discrimination
      ability toward HQ and CC and improved simultaneous detection performance were
      achieved. The linear range for HQ and CC were 1.0*10(-6) to 5.0*10(-4) M and
      1.0*10(-6) to 4.0*10(-4) M, respectively. The detection limit for HQ was 4.0*10(
      7) M and for CC 1.7*10(-7) M (S/N=3), correspondingly.

PMID- 24296142
TI  - Gas purge-microsyringe extraction: a rapid and exhaustive direct microextraction
      technique of polycyclic aromatic hydrocarbons from plants.
AB  - Gas purge-microsyringe extraction (GP-MSE) is a rapid and exhaustive
      microextraction technique for volatile and semivolatile compounds. In this study,
      a theoretical system of GP-MSE was established by directly extracting and
      analyzing 16 kinds of polycyclic aromatic hydrocarbons (PAHs) from plant samples.
      On the basis of theoretical consideration, a full factorial experimental design
      was first used to evaluate the main effects and interactions of the experimental
      parameters affecting the extraction efficiency. Further experiments were carried
      out to determine the extraction kinetics and desorption temperature-dependent.
      The results indicated that three factors, namely desorption temperature
      (temperature of sample phase) Td, extraction time t, and gas flow rate u, had a
      significantly positive effect on the extraction efficiency of GP-MSE for PAHs.
      Extraction processes of PAHs in plant samples followed by first-order kinetics
      (relative coefficient R(2) of simulation curves were 0.731-1.000, with an average
      of 0.958 and 4.06% relative standard deviation), and obviously depended on the
      desorption temperature. Furthermore, the effect of the matrix was determined from
      the difference in Eapp,d. Finally, satisfactory recoveries of 16 PAHs were
      obtained using optimal parameters. The study demonstrated that GP-MSE could
      provide a rapid and exhaustive means of direct extraction of PAHs from plant
      samples. The extraction kinetics were similar that of the inverse process of the
      desorption kinetics of the sample phase. 

PMID- 24296143
TI  - Solubility parameter used to predict the effectiveness of monolithic in-needle
      extraction (MINE) device for the direct analysis of liquid samples.
AB  - The sorbent/eluent systems combined from three macroporous poly(styrene
      divinylbenzene) (PS-DVB) monoliths and four solvents as eluents were used for the
      extraction of phenol, 4-chlorophenol and p-benzochinon from water samples.
      Monolithic in-needle extraction (MINE) devices were used in the preparation of a
      series of test water samples for chromatographic analysis. The extraction of
      phenolic compounds from water samples was carried out by pumping liquid samples
      through the MINE device. Solubility parameter concept was applied for estimation
      of effectiveness of MINE. Solubility parameters for (PS-DVB) monoliths were
      determined according to Small, considering different molar fraction of the
      monomers used for synthesis. Effectiveness of these systems was estimated
      according to difference of solubility parameter value in analyte/sorbent,
      sorbent/eluent, analyte/eluent pairs. The procedure enabling easy prediction of,
      e.g. the strength of the interactions between the analyte and sorbent, eluent
      efficiency or the extraction efficiency in MINE system was proposed. 

PMID- 24296144
TI  - Capabilities and limitations of dispersive liquid-liquid microextraction with
      solidification of floating organic drop for the extraction of organic pollutants
      from water samples.
AB  - Dispersive liquid-liquid microextraction with solidification of floating organic
      drop (DLLME-SFO) is one of the most interesting sample preparation techniques
      developed in recent years. Although several applications have been reported, the
      potentiality and limitations of this simple and rapid extraction technique have
      not been made sufficiently explicit. In this work, the extraction efficiency of
      DLLME-SFO for pollutants from different chemical families was determined. Studied
      compounds include: 10 polycyclic aromatic hydrocarbons, 5 pesticides
      (chlorophenoxy herbicides and DDT), 8 phenols and 6 sulfonamides, thus, covering
      a large range of polarity and hydrophobicity (LogKow 0-7, overall). After
      optimization of extraction conditions using 1-dodecanol as extractant, the
      procedure was applied for extraction of each family from 10-mL spiked water
      samples, only adjusting sample pH as required. Absolute recoveries for pollutants
      with LogKow 3-7 were >70% and recovery values within this group (18 compounds)
      were independent of structure or hydrophobicity; the precision of recovery was
      very acceptable (RSD<12%) and linear behavior was observed in the studied
      concentration range (r(2)>0.995). Extraction recoveries for pollutants with
      LogKow 1.46-2.8 were in the range 13-62%, directly depending on individual LogKow
      values; however, good linearity (r(2)>0.993) and precision (RSD<6.5%) were also
      demonstrated for these polar solutes, despite recovery level. DLLME-SFO with 1
      dodecanol completely failed for extraction of compounds with LogKow<=1 (sulfa
      drugs), other more polar extraction solvents (ionic liquids) should be explored
      for highly hydrophilic pollutants. 

PMID- 24296145
TI  - Chemical dereplication of marine actinomycetes by liquid chromatography-high
      resolution mass spectrometry profiling and statistical analysis.
AB  - Discovery of novel bioactive metabolites from marine bacteria is becoming
      increasingly challenging, and the development of novel approaches to improve the
      efficiency of early steps in the microbial drug discovery process is therefore of
      interest. For example, current protocols for the taxonomic dereplication of
      microbial strains generally use molecular tools which do not take into
      consideration the ability of these selected bacteria to produce secondary
      metabolites. As the identification of novel chemical entities is one of the key
      elements driving drug discovery programs, this study reports a novel methodology
      to dereplicate microbial strains by a metabolomics approach using liquid
      chromatography-high resolution mass spectrometry (LC-HRMS). In order to process
      large and complex three dimensional LC-HRMS datasets, the reported method uses a
      bucketing and presence-absence standardization strategy in addition to
      statistical analysis tools including principal component analysis (PCA) and
      cluster analysis. From a closely related group of Streptomyces isolated from
      geographically varied environments, we demonstrated that grouping bacteria
      according to the chemical diversity of produced metabolites is reproducible and
      provides greatly improved resolution for the discrimination of microbial strains
      compared to current molecular dereplication techniques. Importantly, this method
      provides the ability to identify putative novel chemical entities as natural
      product discovery leads. 

PMID- 24296146
TI  - Ultra-fast cyclosporin A quantitation in whole blood by Laser Diode Thermal
      Desorption-tandem mass spectrometry; comparison with High Performance Liquid
      Chromatography-tandem mass spectrometry.
AB  - In the last decade the quantitation of immunosuppressive drugs has seen vast
      improvements in analytical methods, optimizing time, accuracy of analysis and
      cost. Laser Diode Thermal Desorption (LDTD) coupled to Atmospheric Pressure
      Chemical ionization-tandem mass spectrometry (APCI-MS/MS) represents a
      technological breakthrough that removes the chromatographic separation step and
      thereby significantly increases the analytical throughput for the quantitation of
      cyclosporin A (CsA) in whole blood for therapeutic drug monitoring (TDM). A
      simple protein precipitation step was used prior to depositing 5 MUL of the
      extract on a 96-well LazWellTM plate and CsA was quantified by LDTD-APCI-MS/MS.
      The laser pattern was set to ramp from 0 to 45% laser power within 2 s. The APCI
      parameters were set to negative needle voltage (-2 MUA), carrier gas temperature
      (30 degrees C) and air flow rate (3 L min(-1)). The negative ion single reaction
      monitoring transitions for CsA and its internal standard cyclosporin D (CsD) were
      respectively m/z 1201.1/1088.9 and m/z 1214.8/1102.8; obtained with a collision
      energy of -40 V. The analysis was achieved within 9 s from sample to sample. The
      extraction procedure yielded high recovery (92%; RSD=9.4%, n=6). The lower limit
      of quantitation was fixed at the first level of calibration: 23.5 ng mL(-1)
      (accuracy=112.3%; RSD=9.6%; n=6) and a blank+6 point linear regression up to 965
      ng mL(-1) was used. Using 4 levels of quality control (QC), intra-day assays
      (n=6) ranged from 93.5 to 95.7% (bias) and from 3.4 to 13.1% (RSD) while inter
      day assays (n=6) ranged from 92.9 to 105.3% (bias) and from 4.9 to 7.5% (RSD). An
      inter-sample contamination of CsA of 2.3% was calculated that was considered
      negligible with respect to the range of CsA concentrations. Whole blood samples
      (120) from patients under CsA treatment were analyzed by LDTD-APCI-MS/MS and HPLC
      ESI-MS/MS, the gold standard reference method for CsA quantification. Both
      methods agreed (P>=0.99), with a coefficient of correlation of 0.99 (95%
      confidence interval 0.982-0.991). The Passing-Bablok regression revealed no
      significant deviation from linearity (Cusum test, P=0.11). This method seems
      suitable for use in TDM of CsA.

PMID- 24296147
TI  - A cost-effective and practical polybenzanthrone-based fluorescent sensor for
      efficient determination of palladium (II) ion and its application in agricultural
      crops and environment.
AB  - A highly selective and sensitive fluorescent chemosensor suitable for practical
      measurement of palladium ion (Pd(2+)) in agricultural crops and environment
      samples has been successfully fabricated using polybenzanthrone (PBA). PBA was
      facilely electrosynthesized in the mixed electrolyte of acetonitrile and boron
      trifluoride diethyl etherate. The fluorescence intensity of PBA showed a linear
      response to Pd(2+) in the concentration range of 5 nM-0.12 mM with a detection
      limit of 0.277 nM and quantification limit of 0.925 nM. Different compounds
      existing in agricultural crops and environment such as common metal ions, anions,
      natural amino acids, carbohydrates, and organic acids were used to examine the
      selectivity of the as-fabricated sensor, and no obvious fluorescence change could
      be observed in these interferents and their mixtures. A possible mechanism was
      proposed that the coordination of PBA and Pd(2+) enhance the aggregation of
      polymer chains, which led to a significant quenching of PBA emission, and this
      was further confirmed by absorption spectra monitoring and transmission electron
      microscopy. The excellent performance of the proposed sensor and satisfactory
      results of the Pd(2+) determination in practical samples suggested that the PBA
      based fluorescent sensor for the determination of Pd(2+) will be a good candidate
      for application in agriculture and environment.

PMID- 24296148
TI  - Bimetallic gold-silver nanoplate array as a highly active SERS substrate for
      detection of streptavidin/biotin assemblies.
AB  - The silver-modified gold nanoplate arrays as bimetallic surface-enhanced Raman
      scattering (SERS) substrates were optimized for the surface-enhanced Raman
      detection of streptavidin/biotin monolayer assemblies. The bimetallic gold-silver
      nanoplate arrays were fabricated by coating silver nanoparticles uniformly on the
      gold nanoplate arrays. Depending on silver nanoparticle coating, the localized
      surface plasmon resonance (LSPR) peak of the bimetallic gold-silver nanoplate
      arrays blue-shifted and broadened significantly. The common probe molecule, Niel
      Blue A sulfate (NBA) was used for testing the SERS activity of the bimetallic
      gold-silver nanoplate arrays. The SERS intensity increased with the silver
      nanoparticle coating, due to a large number of hot spots and nanoparticle
      interfaces. The platforms were tested against a monolayer of streptavidin
      functionalized over the bimetallic gold-silver nanoplate arrays showing that good
      quality spectra could be acquired with a short acquisition time. The
      supramolecular interaction between streptavidin (strep) and biotin showed
      subsequent modification of Raman spectra that implied a change of the secondary
      structure of the host biomolecule. And the detection concentration for biotin by
      this method was as low as 1.0 nM. The enhanced SERS performance of such
      bimetallic gold-silver nanoplate arrays could spur further interest in the
      integration of highly sensitive biosensors for rapid, nondestructive, and
      quantitative bioanalysis, particularly in microfluidics.

PMID- 24296149
TI  - Determination of trace ethylene glycol in industrial solvents and lubricants
      using phenyl boronic acid derivatization and multidimensional gas chromatography.
AB  - A practical gas chromatographic approach is introduced for the characterization
      of trace ethylene glycol in industrial solvents and lubricants. The analytical
      approach employs single step derivatization technique that effectively converts
      ethylene glycol to the cyclic boronate ester (2-phenyl-1,3,2-dioxaborolane),
      using phenyl boronic acid as a derivatizing reagent. The separation of the
      derivatized product was achieved by using multidimensional gas chromatography.
      Heavy lubricant matrices like engine crankcase oil were back-flushed to improve
      sample throughput and system cleanliness. Detection and quantitation of 2-phenyl
      1,3,2-dioxaborolane was conducted with mass spectrometry in selected ion
      monitoring mode. Complete analysis is conducted in less than 10 min.
      Reproducibility of retention time was found to be less than 0.05% (n=20).
      Quantitative performance is highly satisfactory, viz. 0.49+/-0.02 mg kg(-1)
      (n=12) and 25.5+/-0.48 mg kg(-1) (n=12) for 0.5 mg kg(-1) and 25 mg kg(-1) spiked
      concentrations respectively. Over a range from 100 MUg kg(-1) to 100 mg kg(-1),
      the response for 2-phenyl-1,3,2-dioxaborolane is linear with correlation
      coefficient of 0.998, a practical detection limit of 50 MUg kg(-1), and average
      spiked recoveries for the analyte in the matrices tested range from 93 to 99%.
      Propylene glycol can also be analyzed using the same approach and water does not
      inhibit the formation of the derivatives, most probably owing to the use of 2,2
      dimethoxypropane as a solvent for the derivatizing agent.

PMID- 24296150
TI  - Quantitative on-line preconcentration-liquid chromatography coupled with tandem
      mass spectrometry method for the determination of pharmaceutical compounds in
      water.
AB  - One of the current environmental issues concerns the presence and fate of
      pharmaceuticals in water bodies as these compounds may represent a potential
      environmental problem. The characterization of pharmaceutical contamination
      requires powerful analytical method able to quantify these pollutants at very low
      concentration (few ng L(-1)). In this work, a multi-residue analytical
      methodology (on-line solid phase extraction-liquid chromatography-triple
      quadrupole mass spectrometry using positive and negative electrospray ionization)
      has been developed and validated for 40 multi-class pharmaceuticals and
      metabolites for tap and surface waters. This on-line SPE method was very
      convenient and efficient compared to classical off-line SPE method because of its
      shorter total run time including sample preparation and smaller sample volume (1
      mL vs up to 1 L). The optimized method included several therapeutic classes as
      lipid regulators, antibiotics, beta-blockers, non-steroidal anti-inflammatories,
      antineoplastic, etc., with various physicochemical properties. Quantification has
      been achieved with the internal standards. The limits of detection are between
      0.7 and 15 ng L(-1) for drinking waters and 2-15 ng L(-1) for surface waters. The
      inter-day precision values are below 20% for each studied level. The improvement
      and strength of the analytical method has been verified along a monitoring of
      these 40 pharmaceuticals in Isle River, a French stream located in the South West
      of France. During this survey, 16 pharmaceutical compounds have been detected.

PMID- 24296151
TI  - Gender-based measurement invariance of the substance use risk profile scale.
AB  - Gender may influence the psychometric properties of psychological and affect
      related measures. The American Psychological Association has made recommendations
      to conduct tests of group-level measurement invariance (MI) before comparing
      scores between groups. Gender-based measurement invariance has been examined in
      many well-known psycho-social scales such as the CES-D and the Big Five
      Inventory. The Substance Use Risk Profile is a 23-item scale measuring affective-
      and personality-related traits known to increase risk for substance use, with 4
      dimensions: anxiety sensitivity, hopelessness, sensation seeking and impulsivity.
      Despite similarities in the constructs assessed by the SURPS, the CES-D and the
      Big Five Inventory, gender-based measurement invariance of the SURPS has not yet
      been published. Multi-group confirmatory factor analysis was used to assess the
      measurement invariance of the four dimensions of the SURPS across gender. MI was
      conducted with M-Plus 6.2 using a 2-step analysis for ordinal variables suggested
      by Muthen and Muthen, and model fit was assessed using the comparative fit index
      (CFI) criteria recommended by Cheung and Rensvold. A single group confirmatory
      factor analysis (CFA) was also conducted. The sample was composed of 1352
      adolescents (56% female, mean age of 14years) participating in the BC Adolescent
      Substance Use Survey, an online survey capturing substance use and psychosocial
      trends in secondary students across British Columbia, Canada. Measurement
      invariance across gender was demonstrated for the SURPS (DeltaCFI=0.003), and the
      single group CFA supported a four-dimensional structure for the SURPS items
      (CFI=0.92, RMSEA=061, 95% CI=0.058-0.065). 

PMID- 24296152
TI  - Surface modification by argon plasma treatment improves antioxidant defense
      ability of CHO-k1 cells on titanium surfaces.
AB  - Titanium is one of the most used materials in implants and changes in its surface
      can modify the cellular functional response to better implant fixation. An argon
      plasma treatment generates a surface with improved mechanical proprieties without
      modifying its chemical composition. Oxidative stress induced by biomaterials is
      considered one of the major causes of implant failure and studies in this field
      are fundamental to evaluate the biocompatibility of a new material. Therefore, in
      this work, induction of oxidative stress by titanium surfaces subjected to plasma
      treatment (PTTS) was evaluated. The viability of CHO-k1 cells was higher on PTTS
      discs. Cells grown on titanium surfaces are subjected to intracellular oxidative
      stress. Titanium discs subjected to the plasma treatment induced less oxidative
      stress than the untreated ones, which resulted in improved cellular survival.
      These were associated with improved cellular antioxidant response in Plasma
      Treated Titanium Surface (PTTS). Furthermore, a decrease in protein and DNA
      oxidative damage was observed on cells grown on the roughed surface when compared
      to the smooth one. In conclusion, our data suggest that the treatment of titanium
      with argon plasma may improve its biocompatible, thus improving its performance
      as implants or as a scaffold in tissue engineering. 

PMID- 24296153
TI  - Effects of antidepressant drugs on synaptic protein levels and dendritic
      outgrowth in hippocampal neuronal cultures.
AB  - The alteration of hippocampal plasticity has been proposed to play a critical
      role in both the pathophysiology and treatment of depression. In this study, the
      ability of different classes of antidepressant drugs (escitalopram, fluoxetine,
      paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine) to mediate
      the expression of synaptic proteins and dendritic outgrowth in rat hippocampal
      neurons was investigated under toxic conditions induced by B27 deprivation, which
      causes hippocampal cell death. Postsynaptic density protein-95 (PSD-95), brain
      derived neurotrophic factor (BDNF), and synaptophysin (SYP) levels were evaluated
      using Western blot analyses. Additionally, dendritic outgrowth was examined to
      determine whether antidepressant drugs affect the dendritic morphology of
      hippocampal neurons in B27-deprived cultures. Escitalopram, fluoxetine,
      paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine significantly
      prevented B27 deprivation-induced decreases in levels of PSD-95, BDNF, and SYP.
      Moreover, the independent application of fluoxetine, paroxetine, and sertraline
      significantly increased levels of BDNF under normal conditions. All
      antidepressant drugs significantly increased the total outgrowth of hippocampal
      dendrites under B27 deprivation. Specific inhibitors of calcium/calmodulin kinase
      II (CaMKII), KN-93, protein kinase A (PKA), H-89, or phosphatidylinositol 3
      kinase (PI3K), LY294002, significantly decreased the effects of antidepressant
      drugs on dendritic outgrowth, whereas this effect was observed only with
      tianeptine for the PI3K inhibitor. Taken together, these results suggest that
      certain antidepressant drugs can enhance synaptic protein levels and encourage
      dendritic outgrowth in hippocampal neurons. Furthermore, effects on dendritic
      outgrowth likely require CaMKII, PKA, or PI3K signaling pathways. The observed
      effects may be may be due to chronic treatment with antidepressant drugs. 

PMID- 24296154
TI  - Long-term heat shock proteins (HSPs) induction by carbenoxolone improves hallmark
      features of Parkinson's disease in a rotenone-based model.
AB  - Protein aggregation and dysfunction of ubiquitin proteasome system (UPS) have
      been implicated in Parkinson's disease (PD) pathology for a long time. Heat shock
      proteins (HSPs) have neuro-protective effects in PD as they assist in protein
      refolding and targeting of irreparable proteins to UPS. To realize their benefits
      in a chronically progressing disease like PD, it is imperative to maintain
      slightly up-regulated levels of HSPs consistently over a longer period of time.
      Here, we evaluate the possible beneficial effects of HSP inducer carbenoxolone
      (cbx) in a rotenone-based rat model of PD. Simultaneously with rotenone, a low
      dose of cbx (20 mg/kg body weight) was administered for five weeks to male SD
      rats. Weekly behavioral analysis along with end-point evaluation of HSPs, UPS
      activity, apoptosis, and oxidative stress were performed. The activation of heat
      shock factor-1 (HSF-1) and up-regulation of HSP70, HSP40, and HSP27 levels in mid
      brain following cbx administration resulted in the reduction of alpha-synuclein
      and ubiquitin aggregation. This decrease seems to be mediated by reduction in
      protein carbonylation as well as up-regulation of UPS activity. In addition, the
      decrease in apoptosis and oxidative stress following HSP upregulation prevented
      the decline in tyrosine hydroxylase (TH) and dopamine levels in mid-brain region,
      which in turn resulted in improved motor functions. Thus, persistent HSP
      induction at low levels by cbx could improve the PD pathophysiology. 

PMID- 24296155
TI  - Paradoxical mineralocorticoid receptor-mediated effect in fear memory encoding
      and expression of rats submitted to an olfactory fear conditioning task.
AB  - There is general agreement that the substantial modification in memory and
      motivational states exerted by corticosteroids after a traumatic experience is
      mediated in complementary manner by the mineralocorticoid (MR) and glucocorticoid
      (GR) receptors. Here we tested the hypothesis that pharmacological manipulation
      of MR activity would affect behavioral strategy and information storage in an
      olfactory fear conditioning (OFC) task. Male Wistar rats were submitted to the
      OFC with different training intensities. We observed that following high
      intensity OFC acquisition, a set of defensive coping strategies, which includes
      avoidance and risk assessment behaviors, was elicited when subjects were exposed
      to the conditioned stimulus (CS) 48 h later. In addition, following either OFC
      acquisition or retrieval (CS-I test) a profound corticosterone secretion was also
      detected. Systemic administration of the MR antagonist spironolactone altered the
      behavioral coping style irrespective the antagonist was administered 60 min prior
      to the acquisition or before the retrieval session. Surprisingly, the MR agonist
      fludrocortisone given 60 min prior to acquisition or retrieval of OFC had similar
      effects as the antagonist. In addition, post-training administration of
      fludrocortisone, following a weak training procedure, facilitated the
      consolidation of OFC. Fludrocortisone rather than spironolactone reduced serum
      corticosterone levels, suggesting that, at least in part, the effects of the MR
      agonist may derive from additional GR-mediated HPA-axis suppression. In
      conclusion, the present study suggests the involvement of the MR in the fine
      tuning of behavioral adaptation necessary for optimal information storage and
      expression, as revealed by the marked alterations in the risk assessment
      behavior. 

PMID- 24296156
TI  - Correspondence to: Bilirubin; a diagnostic marker for appendicitis.

PMID- 24296157
TI  - Statistical factor analysis technique for characterizing basalt through
      interpreting nuclear and electrical well logging data (case study from Southern
      Syria).
AB  - Factor analysis technique is proposed in this research for interpreting the
      combination of nuclear well logging, including natural gamma ray, density and
      neutron-porosity, and the electrical well logging of long and short normal, in
      order to characterize the large extended basaltic areas in southern Syria. Kodana
      well logging data are used for testing and applying the proposed technique. The
      four resulting score logs enable to establish the lithological score cross
      section of the studied well. The established cross-section clearly shows the
      distribution and the identification of four kinds of basalt which are hard
      massive basalt, hard basalt, pyroclastic basalt and the alteration basalt
      products, clay. The factor analysis technique is successfully applied on the
      Kodana well logging data in southern Syria, and can be used efficiently when
      several wells and huge well logging data with high number of variables are
      required to be interpreted. 

PMID- 24296158
TI  - Hardware and software modifications on the Advion NanoTek microfluidic platform
      to extend flexibility for radiochemical synthesis.
AB  - Microfluidic systems are currently receiving a lot of attention in the PET
      radiochemistry field, due to their demonstrated ability to obtain higher
      incorporation yields with reduced total processing time and using a decreased
      amount of precursors. The Advion NanoTek LF was the first commercial microfluidic
      system available for radiochemistry that allows basic parameter optimization to
      be performed. In this paper we report hardware and software modifications that
      would allow better performing procedures, higher product throughput and
      flexibility to utilize the system. In particular, HPLC purification and SPE
      formulation have been fully integrated. 

PMID- 24296159
TI  - VEGF165 modulates proliferation, adhesion, migration and differentiation of
      cultured human outer root sheath cells from central hair follicle epithelium
      through VEGFR-2 activation in vitro.
AB  - BACKGROUND: The functional state of vasculature is tightly controlled by vascular
      endothelial growth factor receptor-2 (VEGFR-2). Recent studies revealed that
      VEGFR-2 is expressed on hair follicle keratinocytes. OBJECTIVE: We proposed to
      investigate its effect on proliferation, adhesion and migration of cultured human
      outer root sheath cells from central hair follicle epithelium. METHODS: These
      studies were undertaken in vitro using human outer root sheath cells from central
      hair follicle epithelium, immunohistochemistry analysis, immunofluorescence
      microscopy, western blot analysis, MTT, trans well analysis, and RT-PCR. RESULTS:
      Our results show that VEGFR-2 is expressed in these cells in vivo and in vitro.
      Furthermore, proliferation and migration of cultured human outer root sheath
      cells from central hair follicle epithelium is increased by VEGF165, while
      homotypic adhesion is decreased but heterotypic adhesion is increased. VEGF165
      upregulates integrin beta1 but dowregulates lgr6 expression. In addition,
      phosphorylation of VEGFR-2, Erk1/2, c-Jun and p38, are increased following
      VEGF165 treatment and these effects are reversed by a VEGFR-2 neutralizing
      antibody. CONCLUSION: Our results suggest a role of VEGF/VEGFR-2 beyond
      angiogenesis in hair follicle regulation.

PMID- 24296160
TI  - Application of FTIR microspectroscopy for characterization of biomolecular
      changes in human melanoma cells treated by sesamol and kojic acid.
AB  - BACKGROUND: Hyperpigmentation is aesthetic undesirable. Sesamol and the standard
      antimelanogenic agent (kojic acid) were shown to hinder melanogenesis by blocking
      tyrosinase and reducing melanin content. OBJECTIVE: The FTIR microspectroscopy
      was used in an attempt to find a novel method to define biological alternation in
      a melanogenesis inhibition of sesamol and kojic acid. METHODS: Tyrosinase
      inhibition and melanin content of sesamol and kojic acid were evaluated. The FTIR
      microspectroscopy was adopted to define the vibrational characteristic involved
      with the melanogenesis in the untreated SK-MEL2 cells vs. the sesamol- and kojic
      treated SK-MEL2 cells. RESULTS: Sesamol and kojic acid inhibited mushroom
      tyrosinase at IC50 of 0.33 MUg/ml and 6.1+/-0.4 MUg/ml, respectively. Moreover,
      30 MUg/ml sesamol inhibited 23.55+/-8.25% cellular tyrosinase activity in human
      SK-MEL2 cells, while 600 MUg/ml kojic acid inhibited 33.9+/-1.4% cellular
      tyrosinase activity in the same cells. In the SK-MEL2-treated with two
      inhibitors, the FTIR spectra assigned to the lipid and nucleic acid bands were
      significantly depleted with the secondary protein structure shifted to a more
      beta-pleated secondary protein one. CONCLUSION: Both sesamol and kojic acid
      display a similar pattern of antimelanogenesis activity albeit to a different
      degree. The mechanism of their whitening effect may be via the alteration of (a)
      the enzyme conformation disallowing the ordinary enzyme-substrate interaction and
      maybe (b) the integrity of the lipid-containing melanosome. Our results support
      the alternative use of FTIR microspectroscopy as a simple and reagent-free method
      for characterization of biomolecular changes in human melanoma cells.

PMID- 24296161
TI  - Education of ICU nurses regarding invasive mechanical ventilation: findings from
      a cross-sectional survey.
AB  - BACKGROUND: Continuing education for intensive care unit nurses on invasive
      mechanical ventilation is fundamental to the acquisition and maintenance of
      knowledge and skills to optimise patient outcomes. PURPOSE: We aimed to determine
      how intensive care unit nurses perceived current education provided on mechanical
      ventilation, including a self-directed learning package and a competency
      programme; identify other important topics and forms of education; and determine
      factors associated with the completion of educational programmes on invasive
      mechanical ventilation. METHODS: A cross-sectional, 30-item, self-administered
      and semi-structured survey on invasive mechanical ventilation education was
      distributed to 160 intensive care nurses. Analysis included descriptive
      statistics and logistic regression was used to determine factors associated with
      current education completion, reported as adjusted odds ratios (AOR) and 95%
      confidence intervals (CIs). FINDINGS: Eighty three intensive care unit nurses
      responded and the majority (63%) reported not receiving education about
      mechanical ventilation prior to working in intensive care. Using a Likert rating
      scale the self-directed learning package and competency programme were perceived
      as valuable and beneficial. Hands-on-practice was perceived as the most important
      form of education and ventilator settings as the most important topic.
      Multivariate analysis determined that older age was independently associated with
      not completing the self-directed learning package (AOR 0.20, 95% CI 0.04, 0.93).
      For the competency programme, 4-6 years intensive care experience was
      independently associated with completion (AOR 17, 95% CI 1.7, 165) and part-time
      employment was associated with non-completion (AOR 0.23, 95% CI 0.08, 0.68).
      CONCLUSION: Registered nurses are commencing their ICU experience with limited
      knowledge of invasive MV therefore the education provided within the ICU
      workplace becomes fundamental to safe and effective practice. The perception of
      continuing education by ICU nurses from this research is positive regardless of
      level of ICU experience and may influence the type of continuing education on
      invasive MV provided to ICU nurses in the future, not only in the ICU involved in
      this study, but other units throughout Australia.

PMID- 24296162
TI  - Prolonged outbreak of Staphylococcus aureus surgical site infection traced to a
      healthcare worker with psoriasis.
AB  - BACKGROUND: Meticillin-sensitive Staphylococcus aureus (MSSA) is a frequent cause
      of surgical site infection (SSI), but point-source outbreaks are rarely
      recognized. AIM: To describe an outbreak of MSSA SSI in a thoracic surgical unit.
      METHODS: An outbreak investigation was started following two postoperative
      bacteraemias with MSSA resistant to fusidic acid (MSSA FusR). Patients with MSSA
      FusR were identified from microbiology records and through prospective case
      finding. Healthcare workers (HCWs) were screened. Isolates were characterized by
      phage typing, spa typing, pulsed-field gel electrophoresis and toxin gene
      profiling. A case-control study examined the association between one HCW with
      MSSA FusR and the patients involved in the outbreak. FINDINGS: Nineteen patients
      were identified with MSSA FusR over 16 months. Four isolates were available for
      typing and all belonged to the same lineage. Seventy-six HCWs were screened. One
      was a carrier of the outbreak strain (a nurse with psoriasis). All 19 cases were
      exposed to this HCW compared with only 40/66 controls (P = 0.003) and cases had a
      greater duration of exposure (P = 0.00001, chi-squared for trend). Direct patient
      contact was documented in 15 cases. The outbreak was halted by thorough cleaning
      of the ward and removal of the HCW from clinical duty. CONCLUSION: The HCW with
      psoriasis was the source of this outbreak. MSSA FusR may be a marker for strains
      associated with skin conditions. HCWs with significant skin conditions may pose
      an infection risk in surgical settings. Recommendations are made for occupational
      health teams regarding screening of HCWs with dermatitis.

PMID- 24296163
TI  - Clinical comparison of a flowable composite and fissure sealant: a 24-month split
      mouth, randomized, and controlled study.
AB  - OBJECTIVES: The aim of this clinical study was to evaluate the retention rate and
      caries-prevention effect of a flowable composite compared to a conventional resin
      based sealant in a young population over a 24-month period. METHODS: Thirty-four
      patients, ranging in age from 16 to 22 years, diagnosed with at least 2 non
      cavitated pit-and-fissure caries in the first and second molars were selected for
      this randomized split-mouth design trial. A total of 220 sealants, were placed in
      117 upper molars and 103 lower molars. The teeth were sealed with a flowable
      resin composite (Tetric Evo Flow) or a sealant material (Helioseal F). Each
      restoration was independently evaluated in terms of retention and the presence of
      caries at baseline and at 1, 6, 12, and 24 months. Data were analyzed using non
      parametric Mann-Whitney U and Friedman 1-way ANOVA tests at p<0.05. RESULTS:
      Tetric Evo Flow showed complete retention with 100%, 95.5%, 93.8%, and 88.5% at
      1, 6, 12, and 24-month evaluations, respectively, while Helioseal F retention
      rates were 98.1%, 95.5%, 94.8%, and 85.4%, respectively, for the same evaluation
      periods. At the 24-month recall, 4 (4.2%) total losses were observed in subjects
      treated with Tetric Evo Flow and 2 total losses (2.1%) for Helioseal F,
      respectively. No significant differences were observed between the materials in
      retention rates or caries incidence for each evaluation period (p>0.05).
      CONCLUSION: Placement of flowable composite as fissure sealants in the younger
      population seems to be as effective as conventional fluoride containing fissure
      sealants for the prevention of fissure caries. CLINICAL RELEVANCE: The use of a
      flowable composite as a fissure sealant material, in conjunction with a total
      etch, single bottle adhesive, yielded better retention than did the conventional
      fluoride containing resin-based fissure sealant over a 24-month period in young
      patients.

PMID- 24296164
TI  - Experimental and FE displacement and polymerization stress of bonded restorations
      as a function of the C-Factor, volume and substrate stiffness.
AB  - OBJECTIVES: To determine the free surface displacement of resin-composite
      restorations as a function of the C-Factor, volume and substrate stiffness, and
      to compare the results with interfacial stress values evaluated by finite element
      analysis (FEA). METHODS: Surface displacement was determined by an extensometer
      using restorations with 4 or 6mm diameter and 1 or 2mm depth, prepared in either
      bovine teeth or glass. The maximum displacement of the free surface was monitored
      for 5 min from the start of photoactivation, at an acquisition rate of 1s(-1).
      Axisymmetric cavity models were performed by FEA. Structural stiffness and
      maximum stresses were investigated. RESULTS: For glass, displacement showed a
      stronger correlation with volume (r=0.771) than with C-Factor (r=0.395, p<0.001
      for both). For teeth, a stronger correlation was found with C-Factor (r=0.709;
      p<0.001) than with volume (r=0.546, p<0.001). For similar dimensions, stress and
      displacement were defined by stiffness. Simultaneous increases in volume and C
      Factor led to increases in stress and surface displacement. Maximum stresses were
      located at the cavosurface angle, internal angle (glass) and at the dentine
      enamel junction (teeth). The displacement of the restoration's free surface was
      related to interfacial stress development. CONCLUSIONS: Structural stiffness
      seems to affect the shrinkage stress at the tooth/resin-composite interface in
      bonded restorations. Deep restorations are always problematic because they showed
      high shear stress, regardless of their width. FEA is the only tool capable of
      detecting shear stress due to polymerization as there is still no reliable
      experimental alternative.

PMID- 24296165
TI  - Oral squamous cell carcinoma in patients twenty years of age or younger--review
      and analysis of 186 reported cases.
AB  - To review the literature on reported cases of squamous cell carcinoma (SCC) of
      the oral cavity in patients twenty-years-of-age or younger. All well-documented
      cases of oral SCC in patients twenty-years-of-age or less, published between 1936
      and 2012, were collected and the clinicopathologic features were evaluated.
      Primary cases of oral SCC were selected. Age, gender, intra-oral subsite were
      recorded. A total of 88 articles describing 186 cases were included. The group of
      otherwise healthy patients had a mean age of 14.08years (range newborn-20years),
      the m:f ratio was 1.36; the oral subsites were the tongue, gingiva, and lower
      lip. A second group of patients who have disorders that predispose to cancer
      development, such as xeroderma pigmentosum, Fanconi's anemia, and a history of
      bone marrow transplant, had a mean age of 13.17years (range 5-20years); the m:f
      ratio was 1.23; the oral subsite was mainly the tongue. There was a slight
      difference between otherwise healthy patients and patients with predisposing
      systemic factors, but this difference was not statistically significant. It
      contrast to adults, there is only a weak predilection for males (m:f ratio of
      1.23-1.36). In the young population SCC occurs most frequently in the tongue,
      followed by gingiva and lips. Unlike in adults, SCC is very uncommon in the floor
      of mouth. Oral SCC may, indeed, occur in patients younger than 20years and
      clinicians should take cognizance of this. Periodical examination of the oral
      cavity of young patients is recommended in cases of systemic diseases that
      predispose to cancer development such as xeroderma pigmentosum, Fanconi's anemia,
      and a history of bone marrow transplant. 

PMID- 24296166
TI  - Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor
      tyrosine kinase signaling.
AB  - Intracellular signaling is mediated by reversible posttranslational modifications
      (PTMs) that include phosphorylation, ubiquitination, and acetylation, among
      others. In response to extracellular stimuli such as growth factors, receptor
      tyrosine kinases (RTKs) typically dimerize and initiate signaling through
      phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling
      effectors are recruited to these phosphotyrosine (pTyr) sites primarily through
      Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review
      describes how these conserved domains specifically recognize pTyr residues and
      play a major role in mediating precise downstream signaling events. 

PMID- 24296167
TI  - Central role of RET in thyroid cancer.
AB  - RET (rearranged during transfection) is a receptor tyrosine kinase involved in
      the development of neural crest derived cell lineages, kidney, and male germ
      cells. Different human cancers, including papillary and medullary thyroid
      carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain
      of-function mutations in RET. Accordingly, RET protein has become a promising
      molecular target for cancer treatment. 

PMID- 24296168
TI  - Translesion DNA synthesis and mutagenesis in prokaryotes.
AB  - The presence of unrepaired lesions in DNA represents a challenge for replication.
      Most, but not all, DNA lesions block the replicative DNA polymerases. The
      conceptually simplest procedure to bypass lesions during DNA replication is
      translesion synthesis (TLS), whereby the replicative polymerase is transiently
      replaced by a specialized DNA polymerase that synthesizes a short patch of DNA
      across the site of damage. This process is inherently error prone and is the main
      source of point mutations. The diversity of existing DNA lesions and the
      biochemical properties of Escherichia coli DNA polymerases will be presented. Our
      main goal is to deliver an integrated view of TLS pathways involving the multiple
      switches between replicative and specialized DNA polymerases and their
      interaction with key accessory factors. Finally, a brief glance at how other
      bacteria deal with TLS and mutagenesis is presented. 

PMID- 24296169
TI  - MHC class II antigen presentation by dendritic cells regulated through endosomal
      sorting.
AB  - For the initiation of adaptive immune responses, dendritic cells present
      antigenic peptides in association with major histocompatibility complex class II
      (MHCII) to naive CD4(+) T lymphocytes. In this review, we discuss how antigen
      presentation is regulated through intracellular processing and trafficking of
      MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes,
      where peptides from endocytosed pathogens can bind. In nonactivated dendritic
      cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT
      machinery to intraluminal vesicles of multivesicular bodies, ultimately leading
      to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked
      when dendritic cells are activated, now allowing its transfer to the cell
      surface. This mode of regulation for MHCII is a prime example of how molecular
      processing and sorting at multivesicular bodies can determine the expression of
      signaling receptors at the plasma membrane. 

PMID- 24296170
TI  - Endocytosis and cancer.
AB  - Endocytosis entails selective packaging of cell-surface proteins, such as
      receptors for cytokines and adhesion components, in cytoplasmic vesicles
      (endosomes). The series of sorting events that determines the fate of
      internalized proteins, either degradation in lysosomes or recycling back to the
      plasma membrane, relies on intrinsic sequence motifs, posttranslational
      modifications (e.g., phosphorylation and ubiquitination), and transient
      assemblies of both Rab GTPases and phosphoinositide-binding proteins. This
      multicomponent process is enhanced and skewed in cancer cells; we review
      mechanisms enabling both major drivers of cancer, p53 and Ras, to bias recycling
      of integrins and receptor tyrosine kinases (RTKs). Likewise, cadherins and other
      junctional proteins of cancer cells are constantly removed from the cell surface,
      thereby disrupting tissue polarity and instigating motile phenotypes. Mutant
      forms of RTKs able to evade Cbl-mediated ubiquitination, along with
      overexpression of the wild-type forms and a variety of defective feedback
      regulatory loops, are frequently detected in tumors. Finally, we describe
      pharmacological attempts to harness the peculiar endocytic system of cancer, in
      favor of effective patient treatment. 

PMID- 24296171
TI  - Epigenetics of ciliates.
AB  - Research using ciliates revealed early examples of epigenetic phenomena and
      continues to provide novel findings. These protozoans maintain separate germline
      and somatic nuclei that carry transcriptionally silent and active genomes,
      respectively. Examining the differences in chromatin within distinct nuclei of
      Tetrahymena identified histone variants and established that transcriptional
      regulators act by modifying histones. Formation of somatic nuclei requires both
      transcriptional activation of silent chromatin and large-scale DNA elimination.
      This somatic genome remodeling is directed by homologous RNAs, acting with an RNA
      interference (RNAi)-related machinery. Furthermore, the content of the parental
      somatic genome provides a homologous template to guide this genome restructuring.
      The mechanisms regulating ciliate DNA rearrangements reveal the surprising power
      of homologous RNAs to remodel the genome and transmit information
      transgenerationally. 

PMID- 24296174
TI  - Invited commentary.

PMID- 24296175
TI  - Invited commentary.

PMID- 24296176
TI  - Invited commentary.

PMID- 24296172
TI  - Replicating damaged DNA in eukaryotes.
AB  - DNA damage is one of many possible perturbations that challenge the mechanisms
      that preserve genetic stability during the copying of the eukaryotic genome in S
      phase. This short review provides, in the first part, a general introduction to
      the topic and an overview of checkpoint responses. In the second part, the
      mechanisms of error-free tolerance in response to fork-arresting DNA damage will
      be discussed in some detail. 

PMID- 24296177
TI  - Invited commentary.

PMID- 24296178
TI  - Invited commentary.

PMID- 24296179
TI  - Invited commentary.

PMID- 24296180
TI  - Invited commentary.

PMID- 24296181
TI  - Invited commentary.

PMID- 24296182
TI  - Invited commentary.

PMID- 24296183
TI  - Invited commentary.

PMID- 24296184
TI  - Invited commentary.

PMID- 24296185
TI  - Invited commentary.

PMID- 24296186
TI  - Minimally invasive resynchronization pacemaker: a pediatric animal model.
AB  - PURPOSE: We developed a minimally invasive epicardial pacemaker implantation
      method for infants and congenital heart disease patients for whom a transvenous
      approach is contraindicated. The piglet is an ideal model for technical
      development. DESCRIPTION: In 5 piglets we introduced a needle through subxiphoid
      approach under thoracoscopic guidance, inserting a wire into the pericardial
      space. Pacing leads were affixed to the left ventricular free wall and left
      atrial appendage. After verifying functionality with atrial and ventricular
      pacing and sensing, animals were euthanized. Pacemaker monitoring occurred daily
      for 4 days in the fifth animal. EVALUATION: Through minimally invasive
      pericardial access, we directly visualized and fixated pacing leads to the left
      ventricle and left atrial appendage, successfully pacing atrium and ventricle.
      Epicardial structures were visualized. One piglet had contralateral pneumothorax,
      which resolved with needle decompression. No other adverse events occurred.
      CONCLUSIONS: Minimally invasive epicardial pacemaker implantation in an infant
      model is feasible and effective. This innovation may be of value for pacing and
      resynchronization in infants and congenital heart disease patients. Survival
      studies with permanent generator implantation are under way.

PMID- 24296187
TI  - Large esophageal fistula closure using an over-the-scope clip: two unique cases.
AB  - Surgical repair of esophageal fistulas is complex and carries a high degree of
      morbidity. Endoscopic management is preferred but has been limited to closure of
      small fistulas in the past. The over-the-scope clip system has been used as an
      effective method for closure of gastrointestinal perforations. Only a few reports
      have shown the successful use of the over-the-scope clip system for closure of
      fistulas. The following are 2 unique cases of successful endoscopic esophageal
      fistula closure using the over-the-scope clip system. 

PMID- 24296188
TI  - Healing of a large bronchoesophageal fistula secondary to hodgkin lymphoma
      managed with a removable esophageal stent.
AB  - We describe the management of a large bronchoesophageal fistula secondary to
      Hodgkin lymphoma with a fully covered self-expanding metallic stent. 

PMID- 24296189
TI  - Pneumothorax as atypical presentation of bronchial carcinoid.
AB  - We present a case of pneumothorax associated with an endobronchial carcinoid
      tumor in a 18-year-old man with dyspnea and chest pain. Additional tests were
      done, identifying in the chest roentgenogram a complete left pneumothorax with
      persistent leak, which was confirmed by computed tomography of the chest, and
      also finding an endobronchial lesion that limited the complete reexpansion of the
      left lung. Surgical excision was performed, and the lesion was identified as a
      typical bronchial carcinoid, with satisfactory outcome after the intervention. 

PMID- 24296190
TI  - Osteoid osteoma of the rib presenting as thoracic outlet syndrome.
AB  - Osteoid osteoma of the rib is a rare condition mostly mentioned in case report
      studies as lesions involving posterior region of the rib causing scoliosis. This
      report presents a 22-year-old man who complained of neurologic thoracic outlet
      syndrome symptoms. The pathologic study of the resected mass of the first rib
      confirmed the diagnosis of osteoid osteoma. This unique presentation of the
      osteoid osteoma as thoracic outlet syndrome suggests that this pathologic
      involvement of the ribs is not confined to the symptoms of pain and scoliosis. 

PMID- 24296191
TI  - Extended resection of a plasmocytoma of bone and an amyloidoma of the chest wall.
AB  - Solitary plasmocytoma of bone is a rare condition of plasma cell neoplasia that
      presents as a single lesion. Amyloidoma of the chest wall is an uncommon
      presentation of solitary tissue amyloid deposition in the absence of systemic
      light-chain amyloidosis. This report describes a patient with both uncommon
      conditions. The tumor originated from the spine and invaded the right lung. In
      this exceedingly rare case, radiotherapy and a two-step resection of the right
      lower lobe, full-thickness chest wall, diaphragm, and vertebral body of T9
      provided local control of the tumor. Spondylodesis of T7 to T11 provided spine
      stability. 

PMID- 24296192
TI  - Endobronchial valve placement for spontaneous pneumothorax from stage IIIA non
      small cell lung cancer facilitates neoadjuvant therapy.
AB  - Spontaneous pneumothorax has previously been described as a presenting symptom of
      lung cancer. This presentation can, unfortunately, complicate and delay further
      definitive oncologic care until the pneumothorax can be effectively managed. We
      describe the case of a 58-year-old man who presented with secondary spontaneous
      pneumothorax and persistent air leak related to his primary lung carcinoma.
      Endobronchial valve placement allowed for the avoidance of pleurodesis, timely
      discharge, and neoadjuvant chemotherapy, followed by definitive surgical
      resection. 

PMID- 24296193
TI  - Right lower lobectomy with middle lobe preservation after right upper lobectomy
      in lung cancer of the right lower lobe.
AB  - A 73-year-old woman who underwent right upper lobectomy for tuberculosis 40 years
      earlier was diagnosed with adenocarcinoma, clinical stage IIA (T2bN0M0), in the
      right lower lobe of her lung. A lower lobectomy with preservation of the middle
      lobe was performed. The patient had an uneventful recovery. She is alive without
      signs of recurrence or requirement for additional oxygen support 6 years after
      the operation. 

PMID- 24296194
TI  - Semiautologous repair for congenital discontinuous right pulmonary artery.
AB  - Unilateral absence of a proximal pulmonary artery (UAPA) is rare and occurs in an
      isolated form or in the presence of other cardiovascular anomalies. There is a
      paucity of literature describing surgical correction of this anomaly. Most
      commonly, a primary anastomosis between the main and proximal right pulmonary
      arteries has been described. However, in cases of long-gap discontinuity, this
      can be difficult and may result in excess tension on the anastomosis,
      predisposing to decreased patency. We present a novel technique by which
      discontinuity in the right pulmonary artery (RPA) is surgically corrected in a
      semiautologous fashion using a main pulmonary artery (MPA) flap. 

PMID- 24296195
TI  - Hypoplastic left ventricle and scimitar syndrome.
AB  - Hypoplastic left ventricle with scimitar syndrome is a rare combination of
      anatomic lesions. Five patients with this anatomy have been followed up at our
      institution. Four of these patients are alive: 2 after heart transplant, 1
      underwent a Norwood operation, and 1 has survived staged palliation, culminating
      in a Fontan operation. 

PMID- 24296196
TI  - Off-pump total arterial revascularization for anomalous origin of the left
      coronary artery from the pulmonary artery.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is a rare
      but potentially lethal congenital anomaly, especially if presented later in
      adulthood. We report a previously healthy young man who had a sudden cardiac
      arrest at a Zumba class, was resuscitated, and was successfully treated with off
      pump total arterial revascularization and ligation of the left main stem of
      anomalous origin. 

PMID- 24296197
TI  - Left atrium ball thrombus in a patient with hemorrhagic cerebral infarction.
AB  - The patient was a 72-year-old man with left hemiparesis. Multiple hemorrhagic
      cerebral infarctions were recognized on a computed tomographic (CT) scan. A
      transesophageal echocardiogram showed a huge left atrial mass, which was floating
      and nearly obstructed the mitral orifice in the diastolic phase. Emergency left
      atrial mass removal was performed. To reduce the risk of critical brain
      hemorrhage, the dose of heparin was reduced (100 U/kg) and 1 mg/kg/h of
      nafamostat mesilate was administered into the venous circuit during
      extracorporeal circulation. A postoperative brain CT scan showed no evidence of
      deterioration of cerebral hemorrhage. Pathologic examination showed a ball
      thrombus. 

PMID- 24296198
TI  - Successful repair of a mitral valve aneurysm with cleft of anterior mitral
      leaflet in an adult.
AB  - A 40-year-old woman was admitted with severe mitral regurgitation (MR) and atrial
      fibrillation. Preoperative 3-dimensional transesophageal echocardiography
      demonstrated severe MR with an unruptured mitral valve aneurysm and a cleft. The
      stiff cleft edge was removed and closed directly, and plication of the aneurysm
      was added. After the implantation of a semirigid full ring, there was no residual
      MR. An adult patient with MR involving an unruptured mitral valve aneurysm with a
      cleft not associated with infection or a congenital anomaly is extremely rare.
      The 3-dimensional transesophageal echocardiography modality is useful for mitral
      valve repair because it provides precise anatomic information preoperatively. 

PMID- 24296199
TI  - Giant aneurysm of the left atrial branch of the left circumflex artery with
      fistula.
AB  - Giant coronary artery aneurysm with a fistula is a rare condition. We present one
      of the largest aneurysms of left circumflex coronary artery territory, arising
      from the left atrial branch of the left circumflex coronary artery. It had a
      maximum diameter of 10 cm, with a fistulous connection to the right atrium. Total
      exclusion of the aneurysmal mass was achieved by ligation of the afferent artery,
      closure of the entry point from within the aneurysm, and closure of the fistulous
      communication from within the right atrium. The patient's postoperative course
      was uneventful. 

PMID- 24296200
TI  - Annuloaortic ectasia in a patient with congenital absence of the left
      pericardium.
AB  - We report a patient with congenital absence of the left pericardium with
      development of progressive annuloaortic ectasia and aortic insufficiency during a
      12-year period. The patient was treated with a Bentall procedure. Pathologic
      examination of the aorta revealed cystic medial necrosis. The surgical management
      and a possible association between congenital absence of pericardium and Marfan
      syndrome are discussed. 

PMID- 24296201
TI  - Left ventricular assist device and heart transplantation in hemophilia a patient.
AB  - We report here a hemophilia patient who was bridged with a left ventricle assist
      device and later received heart transplantation. Preparation for surgery with
      factor VIII supplementation, intraoperative conduct of surgery, and challenges of
      postoperative course are described with a brief literature review. 

PMID- 24296202
TI  - Apical schwannoma presenting as harlequin syndrome.

PMID- 24296203
TI  - Cracking the coconut: extensive calcification of the left atrium.

PMID- 24296204
TI  - An undescribed pathophysiologic mechanism: redissection of the remaining
      adventitia of a false lumen.

PMID- 24296205
TI  - Surgical extraction of fragmented stent and guidewire after angioplasty.

PMID- 24296206
TI  - Techniques of right extended pneumonectomy.
AB  - Tracheal sleeve pneumonectomy is considered the operation of choice for tumors
      involving the right tracheobronchial angle, even though the procedure is burdened
      by a high rate of perioperative morbidity and mortality. In this report, we
      present our experience with two different techniques to avoid sleeve
      pneumonectomy: the tangential tracheal suture and the tracheoplasty. 

PMID- 24296207
TI  - Repair of tracheal aspergillosis perforation causing tension pneumothorax.
AB  - Tracheobronchial aspergillosis is a rare entity mainly observed in immune
      compromised patients or those who have undergone transplantation. It may cause
      airway ulcerations or bleeding. We report the case of a 17-year-old patient
      receiving chemotherapy for acute lymphoblastic leukemia who presented with right
      sided tension pneumothorax. Chest tube drainage revealed a massive air leak
      without reexpansion of the lung, and bronchoscopy showed a 15- * 15-mm defect of
      the distal trachea related to aspergillosis infection. The defect was closed by
      an intrathoracic transposition of a pedicled latissimus dorsi muscle flap, which
      was sutured into the debrided defect followed by temporary endotracheal stenting
      and antifungal medication. 

PMID- 24296208
TI  - Safe, effective off-pump sternal sparing approach for HeartMate II exchange.
AB  - As left ventricular assist devices (LVADs) have become more widely used for
      treating patients with advanced heart failure, the incidence of pump dysfunction
      requiring pump replacement has increased. When dysfunction is due to pump failure
      or driveline injury, isolated pump replacement can be curative. We have developed
      a quick, safe pump-exchange technique that avoids a redo sternotomy and
      cardiopulmonary bypass. We have used this technique to exchange malfunctioning
      HeartMate II LVADs in 14 consecutive patients. The patients were extubated within
      3 to 6 hours, and blood loss and transfusion requirements were nominal. There
      were no periprocedural deaths or strokes. 

PMID- 24296209
TI  - Reply: To PMID 23295043.

PMID- 24296210
TI  - Influence of intraoperative bleeding during video-assisted thoracic surgery for
      non-small cell lung cancer.

PMID- 24296211
TI  - Choosing postoperative echocardiograms wisely: harmonization of the guidelines.

PMID- 24296212
TI  - Predictors of survival in postinduction therapy surgical T4N0-2 non-small cell
      lung cancer.

PMID- 24296213
TI  - Devices are only as safe as the surgeons who use them.

PMID- 24296214
TI  - Warm blood microplegia redosing interval in pediatric surgery.

PMID- 24296215
TI  - Challenge of neonatal myocardial protection.

PMID- 24296216
TI  - Reply: To PMID 23462260.

PMID- 24296217
TI  - Reply: To PMID 24296215.

PMID- 24296218
TI  - Reduction of sternal infection in off-pump CABG by modified pedicle harvesting.

PMID- 24296219
TI  - Reply: To PMID 23352296.

PMID- 24296220
TI  - Does the optimal time interval between cardiac catheterization and operation in
      patient undergoing cardiac surgery exist?

PMID- 24296221
TI  - Reply: To PMID 23201106.

PMID- 24296222
TI  - Surgical removal of extensive left pulmonary vein stump thrombus after pulmonary
      lobectomy: a rare cause of acute cerebral embolism.
AB  - A 46-year-old woman presented with loss of consciousness and was diagnosed with
      acute cerebral embolism. She had undergone left upper lobectomy for primary lung
      cancer 6 months before this event. Transesophageal echocardiography and computed
      tomography showed a large mobile thrombus in the left upper pulmonary vein
      (LSPV). An emergent operation was performed through a median sternotomy.
      Cardiopulmonary bypass was performed and the heart was arrested, and the LSPV was
      incised. A fresh thrombus had formed in the stump of the LSPV and was removed
      successfully. The postoperative course was uneventful. During a 1 year of follow
      up, there was no recurrence of the thrombus. 

PMID- 24296223
TI  - A completely resected paraganglioma arising from the right atrioventricular
      groove.
AB  - We report a case of completely resected right atrioventricular groove
      paraganglioma. Primary cardiac paragangliomas are extremely rare. Only about 60
      cases have been reported in the literature, and most of these tumors originated
      from the left atrium or the base of the aortic root and pulmonary artery; 5 cases
      originated from the right atrium. In our patient, the paraganglioma was largely
      located in the right atrioventricular groove and protruded into the right atrial
      wall. To our knowledge, there has been no paraganglioma reported in the right
      atrioventricular groove. We successfully carried out complete tumor resection.
      Most of these tumors are locally invasive, and complete resection is often
      difficult. 

PMID- 24296224
TI  - Novel beating heart repair for anomalous origin of right coronary artery.
AB  - Anomalous origin of the right coronary artery (ARCA) from the left coronary sinus
      is a rare anatomic anomaly. It may cause myocardial ischemia and sudden death.
      Several treatments have been tried, including coronary bypass grafting,
      unroofing, and reimplantation. These techniques, however, have disadvantages such
      as postoperative flow competition, aortic insufficiency, or kinks and angulation
      of the coronary artery, respectively. To overcome these problems, we undertook a
      novel approach: beating heart repair. It does not require aortic cross-clamping,
      cardioplegic arrest, aortotomy, or manipulation of the aortic commissure. Beating
      heart repair is a simple and effective procedure, which adds an ideal treatment
      option for ARCA. 

PMID- 24296225
TI  - Intermittent tethering of second-order chords after mitral valve repair for
      bileaflet prolapse.
AB  - Mitral valve regurgitation which occurs immediately after repair can be due to
      anatomic (failure of repair) or functional (systolic anterior motion) reasons. We
      report a case where a patient with bileaflet prolapse showed, after surgical
      correction of the disease, moderate to severe regurgitation after cardiopulmonary
      bypass was stopped. The regurgitation was due to second-order tethering and was
      successfully treated with second-order chordal cutting. 

PMID- 24296226
TI  - Acute aortic regurgitation caused by spontaneous aortic valve rupture.
AB  - We report a rare case that manifested as severe aortic regurgitation (AR)
      resulting from spontaneous aortic valve (AV) rupture caused by valvular
      myxomatous transformation in a middle-aged woman. Before operation, 1 ruptured
      hole on the left coronary cusp (LLC) was clearly visualized with transesophageal
      echocardiography (TEE). There were no clinical findings of vegetations or sinus
      Valsalva aneurysms. The patient was treated successfully with mechanical AV
      replacement. Prompt imaging evaluation is mandatory in this rare critical
      situation for correct diagnosis and appropriate management. 

PMID- 24296227
TI  - Transapical angiography in a patient with severe aortic stenosis undergoing
      transapical transcatheter aortic valve implantation.
AB  - Transapical transcatheter aortic valve implantation (TA-TAVI) is the method of
      choice in patients with severe stenosis of the aortic valve, high operative risk,
      and an adverse peripheral vasculature. The procedure is generally guided by
      peripheral arterial access angiography. We report on a 71-year-old patient in
      whom, because of the absence of an alternative peripheral arterial access route,
      TA-TAVI was supported by the apical insertion of the angiography catheter. This
      approach was effective and safe, and proper valve deployment was feasible without
      unexpected procedural complications. 

PMID- 24296228
TI  - Perceval sutureless valve in freestyle root: new surgical valve-in-valve therapy.
AB  - Aortic root replacement with biological conduit (homograft, autograft, or
      xenograft) is a valuable tool, but biological valves are often prone to
      degeneration. Reoperations usually require root removal and repetition of the
      Bentall procedure to maintain the same orifice area. A less radical option is to
      limit replacement to the valve. In cases of calcified or very small roots,
      standard valve implantation cannot be performed, and bailout with a sutureless
      valve may be a particularly useful option. Here we have described a case of
      leaflet rupture in a calcified small Freestyle root (Medtronic Inc, Minneapolis,
      MN) in which we performed a valve-in-valve (V-in-V) procedure with a Perceval-S
      prosthesis (Sorin Group, Saluggia, Italy). 

PMID- 24296229
TI  - Nonossifying fibroma of rib.

PMID- 24296231
TI  - An efficient way to make a trileaflet conduit for pulmonary valve replacement.
AB  - Pulmonary regurgitation after repair of tetralogy of Fallot has always been an
      important issue for pediatric cardiac surgeons. Some of the patients may need
      pulmonary valve replacement in the future. Conventional prosthesis valves were
      seldom custom made for the pulmonary valve and were often inadequate to use
      because of variable age and size of these patients. Through evolution of
      techniques, we have developed a simple, efficient, and theoretically anatomic way
      of constructing trileaflet polytetrafluoroethylene valved conduit used for right
      ventricle outflow tract reconstruction. It was surprisingly straightforward, time
      efficient, and capable of being produced in various sizes. 

PMID- 24296230
TI  - Successful management of penetrating injury to the aortopulmonary window.

PMID- 24296232
TI  - A DSC and FTIR spectroscopic study of the effects of the epimeric 4-cholesten-3
      ols and 4-cholesten-3-one on the thermotropic phase behaviour and organization of
      dipalmitoylphosphatidylcholine bilayer membranes: comparison with their 5
      cholesten analogues.
AB  - We present the results of a comparative differential calorimetric and Fourier
      transform infrared spectroscopic study of the effect of cholesterol and five of
      its analogues on the thermotropic phase behaviour and organization of
      dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ
      in both the nature and stereochemistry of the polar head group at C3 (betaOH,
      alphaOH or C=O) and in the position of the double bond (C4-C5 in ring A or C5-C6
      in ring B). In the three Delta(5) sterols/steroid series, the concentration of
      these compounds required to abolish the DPPC pretransition, inversely related to
      their relative ability to disorder gel state DPPC bilayers, decreases in the
      order betaOH>alphaOH>C=O and these differences in concentration are significant.
      However, in the Delta(4) series, these concentrations are more similar,
      regardless of polar head group nature or stereochemistry. Similarly, the residual
      enthalpy of the main phase transition of DPPC at 50 mol.% sterol/steroid, which
      is inversely related to the miscibility of these compounds in the DPPC bilayer,
      also increases in the order betaOH>alphaOH>C=O, but this effect is attenuated in
      the Delta(4) as opposed to the Delta(5) series. Both of these results indicate
      that the presence of a double bond at C4-C5 in ring A, as compared to a C5-C6
      double bond in ring B, reduces the effect of variations in the structure of the
      polar group at C3 on the properties of the host DPPC bilayer. The movement of the
      double bond from C5 to C4 in the two sterol pairs results in a greater decrease
      in the temperature and enthalpy of both the pretransition and the main phase
      transition, whereas the opposite result is observed in the ketosteroid pair.
      Similarly, the ability of these compounds to order the DPPC hydrocarbon chains
      decreases in the order betaOH>alphaOH>C=O in both series of compounds, but in the
      two sterol pairs, hydrocarbon chain ordering is greater for the Delta(5) than the
      Delta(4) sterols, whereas the opposite is the case for the steroid pair. All of
      these results indicate that the typical effects of sterols/steroids in increasing
      the packing density and thermal stability of fluid lipid bilayers are optimal
      when an OH group rather than C=O group is present at C3, and that this OH group
      is more effective in the equatorial rather than the axial orientation. We can
      explain all of our sterol results by noting that the shift of the double bond
      from Delta(5) to Delta(4) introduces of a bend in ring A, which in turn destroys
      the coplanarity of the steroid fused ring system and reduces the goodness of
      sterol packing in the host DPPC bilayer. However, this conformational change
      should also occur in the ketosteroid pair, yet our experimental results indicate
      that the presence of the Delta(4) double bond is less disruptive than a double
      bond at Delta(5). We suggest that the presence of keto-enol tautomerism in the
      conjugated Delta(4) ketosteroid, but not in the nonconjugated Delta(5) compound,
      may provide additional H-bonding opportunities to adjacent DPPC molecules in the
      bilayer, which can overcome the unfavourable conformational change in ring A
      induced by the Delta(4) double bond.

PMID- 24296233
TI  - Topical application/formulation of probiotics: will it be a novel treatment
      approach for diabetic foot ulcer?
AB  - Treatment of chronic conditions like diabetic foot ulcer (DFU) is challenging due
      to increased susceptibility for infection and delayed wound healing. Complexity
      of existing therapy, adverse effects and microbial resistance emphasizes the need
      of an alternative approach for the management of DFU. The increasing body of
      evidence associated with probiotic application in diverse disease states merits
      its use in wound healing and infection too. Different probiotic strains have
      shown their efficacy in various infections like gut infections, oral infections
      and urogenital infections. Experimental studies have demonstrated probiotics'
      ability for gastric ulcer healing. Underlying mechanism of the above therapeutic
      effects of probiotics involves modulation of local and systemic immunity. The
      hypothesis is based on the concept that mechanism of anti-infective and ulcer
      healing action of probiotics will be similar in peripheral wounds and ulcers as
      on any other part of the body. This paper focuses on the hypothesis that topical
      applications/formulation of probiotics may be effective for the treatment of
      diabetic foot ulcers. 

PMID- 24296234
TI  - Asymmetrical movements of the lumbopelvic region: is this a potential mechanism
      for low back pain in people with lower limb amputation?
AB  - Low back pain (LBP) is a major secondary disabling condition following lower limb
      amputation including persons with above-knee and below-knee amputation. Whilst
      the increasing prevalence of this musculoskeletal problem in people with lower
      limb amputation is well recognised, the mechanisms of LBP in this population have
      been poorly explored. Asymmetrical movements and loading patterns have been found
      in persons following lower limb amputation and linked to the high prevalence of
      LBP in this population. However, some argue that such asymmetries are part of the
      'normal' adaptive process following lower limb amputation. We hypothesise that
      there is potential for some of the kinematic and kinetic adaptations in the
      lumbopelvic and trunk region to be 'mal-adaptive', potentially acting as a
      contributing factor for the onset or maintenance of LBP symptoms in this
      population. Evidence for movement and muscle asymmetries around the lumbopelvic
      and lower limb region provides some support for an association between LBP and
      movement asymmetry in the general population. It is therefore reasonable to
      hypothesise that movement asymmetries will demonstrate an association with LBP in
      lower limb amputee populations. Previous studies investigating movement and
      loading patterns within this population have focused mainly on gait analysis.
      Therefore, there is a need for further research to investigate the presence and
      potential association of asymmetrical movement patterns of the lumbopelvic region
      with LBP in a range of specific functional tasks. Results of such studies will
      identify the asymmetrical movement patterns and functional tasks associated with
      LBP in this population. Furthermore, it will inform future case-control and
      longitudinal studies to specifically investigate the putative links for such
      asymmetrical movement patterns as risk factors to LBP in this population.

PMID- 24296235
TI  - Magnetite in dura and pia mater in human brain. A shield against electromagnetic
      radiation?

PMID- 24296236
TI  - Early treatment of Kallmann syndrome may prevent eunuchoid appearance and
      behavior.
AB  - Kallmann syndrome (KS) is a genetic disorder which combines hypogonadotropic
      hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced
      levels of gonadotropin-releasing hormone and anosmia due to olfactory bulb
      aplasia. KS treatment usually begins just before puberty, but brain sexual
      maturation occurs long before puberty normally at perinatal age. As brain cells
      implicated in the development of the olfactory and reproductive system have a
      rostral and a caudal origin, and the rostral origin is affected by aplasia in KS
      and the caudal origin does not seem to be affected, the early treatment of KS, as
      proposed in this paper, is to attain brain sexual maturation at the most
      appropriate age possible to prevent the eunuchoid behavior and appearance
      observed in KS. 

PMID- 24296237
TI  - Air pollution as a potential causative factor in the shifting histologic subtypes
      of thoracic malignancies.

PMID- 24296238
TI  - It's all in the mind! Or is it? Positive acupuncture responses in patients with
      dementia: a series of case reports.
AB  - Controversy continues over whether or not there is any real effect from
      acupuncture over and above that of placebo. However, this series of case studies
      may provide us with evidence from an unlikely source. Anticipation of clinical
      benefit is a major element of placebo, and clearly cognition is needed to
      experience this. This raises the question of how much placebo effect is
      experienced by a patient with dementia. These cases document reliably witnessed
      responses to acupuncture in patients with impaired cognition, which have been
      reproducible and maintained. Given the similarity of responses, it could be
      argued that these reports provide evidence of a 'real' effect of acupuncture, and
      raise the possibility of including patients with dementia in formal studies from
      which they might routinely be excluded. 

PMID- 24296239
TI  - Mineral particle size in children with osteogenesis imperfecta type I is not
      increased independently of specific collagen mutations.
AB  - Osteogenesis imperfecta (OI) type I represents the mildest form of OI and is
      usually caused by two classes of autosomal dominant mutations in collagen type I:
      haploinsufficiency leading to a reduced quantity of structurally normal collagen
      (quantitative mutation), or sequence abnormalities generating structurally
      aberrant collagen chains (qualitative mutation). An abnormally high bone matrix
      mineralization has been observed in all OI cases investigated so far,
      independently of mutation type. This raises the question whether the increased
      amount of mineral is due to mineral particles growing to larger sizes or to a
      higher number of more densely packed particles. For this reason, we revisit the
      problem by investigating the mineral particle size in cancellous bone from two
      subsets of the previously analyzed biopsies (patient's age: 2-4.2 and 7.6
      11years) comparing OI quantitative mutations (n=5), OI qualitative mutations
      (n=5) and controls (n=6). We used a combined small-angle X-ray scattering (SAXS)
      and wide-angle X-ray diffraction (WAXD) setup with a beam diameter of 10MUm of
      synchrotron radiation, which allows the determination of mineral particle
      characteristics in 10MUm thick sections at the same positions where the matrix
      mineralization density was previously determined. The thickness parameter of
      mineral particles (T) was obtained from SAXS data and the mineral volume fraction
      was calculated from the mean calcium content of the bone matrix determined by
      quantitative back-scattered electron imaging (qBEI). The combination of these two
      quantities allowed calculating the true particle width (W) of the plate-like
      mineral crystals. T was larger in the older than in the younger age-group
      independently of genotype (p<0.004) and was larger in the controls than in each
      OI group. The qBEI results showed that the mineral volume fraction increased from
      32.45wt.% in controls to 36.44wt.% in both OI groups (corresponding to a 12%
      increase in relative terms). Combining these data, we find that also W was larger
      in the older than in the younger age-group (p<0.002), but stayed equal or smaller
      in both OI genotypes (controls: 2.3nm+/-0.04, OI qualitative: 2.2+/-0.05; OI
      quantitative 2.3+/-0.04, mean+/-SEM). A linear regression analysis even suggests
      a slower increase of W in qualitative OI as compared to quantitative OI and
      controls, where the particle sizes stayed similar at all ages. We thus conclude
      that the high mineral density in human OI is not due to increased particle size
      but rather to increased particle packing density. The lack of an observed
      difference between the two classes of mutations suggests the occurrence of a bone
      cell defect downstream of the collagen mutation. 

PMID- 24296240
TI  - Visualization of ecdysteroid activity using a reporter gene in the crustacean,
      Daphnia.
AB  - Ecdysone is a hormone known to play a pivotal role in crustaceans and insects. In
      order to evaluate the ecdysone activities in the environment and within the
      organism, we have developed a biomonitoring Daphnia strain by introducing a
      reporter gene. In this study, the ecdysone response element was inserted in the
      upstream region of a reporter gene, and the DNA construct was injected into
      Daphnia eggs. The expression of the reporter gene was detected during the early
      embryonic development stage. In addition, when the eggs expressing the reporter
      gene were exposed to ecdysone, there was enhanced expression of the reporter gene
      at detectable levels, while the presence of an antagonist led to its
      downregulation. These results suggested that this system could be potentially
      developed for monitoring ecdysone activities in media. 

PMID- 24296241
TI  - Identification of a CYP3A-like gene and CYPs mRNA expression modulation following
      exposure to benzo[a]pyrene in the bivalve mollusk Chlamys farreri.
AB  - In this study, we isolated a CYP3A-like gene from ovary of the scallop (Chlamys
      farreri). High levels of CYP3A-like gene expression occur in the digestive gland
      and gonad, which suggested their role in the metabolism of steroids and
      xenobiotics. Scallops were exposed to a polycyclic aromatic hydrocarbons (PAHs),
      benzo[a]pyrene (B[a]P) for 10 days. The CYP4 and CYP3A-like gene can be up
      regulated by B[a]P in a dose-dependent manner after 10 days exposure. But no
      induction of the CYP3A-like was observed in 10 MUg/L B[a]P group. The CYP1A-like
      expression can only be induced by 0.025 MUg/L B[a]P. 0.5 and 10 MUg/L B[a]P
      caused significant DNA damage and 10 MUg/L B[a]P can also lead to oxidative
      damage. These results demonstrate that the mollusk CYPs can be modulated by
      environmental pollutant, and the blocked induction of CYP3A-like and CYP1A-like
      expression probably results from the high genotoxicity and oxidative damage
      partly. 

PMID- 24296242
TI  - Muscular cholinesterase and lactate dehydrogenase activities in deep-sea fish
      from the NW Mediterranean.
AB  - Organisms inhabiting submarine canyons can be potentially exposed to higher
      inputs of anthropogenic chemicals than their counterparts from the adjacent
      areas. To find out to what extend this observation applies to a NW Mediterranean
      canyon (i.e. Blanes canyon) off the Catalan coast, four deep-sea fish species
      were collected from inside the canyon (BC) and the adjacent open slope (OS). The
      selected species were: Alepocephalus rostratus, Lepidion lepidion, Coelorinchus
      mediterraneus and Bathypterois mediterraneus. Prior to the choice of an adequate
      sentinel species, the natural variation of the selected parameters (biomarkers)
      in relation to factors such as size, sex, sampling depth and seasonality need to
      be characterised. In this study, the activities of cholinesterases (ChEs) and
      lactate dehydrogenase (LDH) enzymes were determined in the muscle of the four
      deep-sea fish. Of all ChEs, acetylcholinesterase (AChE) activity was dominant and
      selected for further monitoring. Overall, AChE activity exhibited a significant
      relationship with fish size whereas LDH activity was mostly dependent on the sex
      and gonadal development status, although in a species-dependent manner. The
      seasonal variability of LDH activity was more marked than for AChE activity, and
      inside-outside canyon (BC-OS) differences were not consistent in all contrasted
      fish species, and in fact they were more dependent on biological traits. Thus,
      they did not suggest a differential stress condition between sites inside and
      outside the canyon. 

PMID- 24296243
TI  - Long-chain metabolites of alpha-tocopherol occur in human serum and inhibit
      macrophage foam cell formation in vitro.
AB  - Despite intensive research the physiological role and molecular mechanisms of
      action of the lipophilic antioxidant alpha-tocopherol (alpha-TOH) are still
      poorly understood. Hepatic alpha-TOH catabolism results in intermediate formation
      of the long-chain metabolites (alpha-LCMs) alpha-13'-hydroxy- and alpha-13'
      carboxychromanol (alpha-13'-OH and alpha-13'-COOH). We propose that alpha-LCMs
      have biological functions that need further exploration. Here we report that
      alpha-13'-COOH, as detected by LC/MS Q-TOF, occurs in human serum, providing
      evidence for its systemic bioavailability. Using semisynthetically derived alpha
      LCMs we performed flow cytometric analyses and found that alpha-LCMs decrease
      oxidized LDL (oxLDL) uptake (alpha-13'-OH, 24+/-6%, alpha-13'-COOH, 20+/-5% vs
      control) and oxLDL-induced lipid accumulation in human macrophages in vitro
      (alpha-13'-OH, 26+/-4%, alpha-13'-COOH, 21+/-9% vs oxLDL), probably owing to
      alpha-LCM-mediated reduction in phagocytosis of oxLDL (alpha-13'-OH, 16+/-6%,
      alpha-13'-COOH, 41+/-3% vs oxLDL). At the same time, alpha-LCMs induced
      expression of CD36, the major scavenger receptor for oxLDL, in human macrophages
      by about 4.5-fold. Blocking experiments provided evidence that alpha-LCMs
      influence oxLDL uptake independent of CD36. A key finding of our study is that
      bioactivity of the alpha-LCMs occurs at lower concentrations and with mechanisms
      distinct from those of their metabolic precursor alpha-TOH. Our findings shed new
      light on the mechanistic aspects of alpha-TOH function in macrophages, which seem
      to be complicated by circulating alpha-LCMs. We speculate that alpha-LCMs
      represent a new class of regulatory metabolites. Further studies are required to
      elucidate their physiological role and contribution to cardiovascular disease. 

PMID- 24296244
TI  - Accelerated clinical course of prion disease in mice compromised in repair of
      oxidative DNA damage.
AB  - The detailed mechanisms of prion-induced neurotoxicity are largely unknown. Here,
      we have studied the role of DNA damage caused by reactive oxygen species in a
      mouse scrapie model by characterizing prion disease in the ogg1(-/-)mutyh(-/-)
      double knockout, which is compromised in oxidative DNA base excision repair. Ogg1
      initiates removal of the major oxidation product 8-oxoguanine (8-oxoG) in DNA,
      and Mutyh initiates removal of adenine that has been misincorporated opposite 8
      oxoG. Our data show that the onset of clinical signs appeared unaffected by Mutyh
      and Ogg1 expression. However, the ogg1(-/-)mutyh(-/-) mice displayed a
      significantly shorter clinical phase of the disease. Thus, accumulation of
      oxidative DNA damage might be of particular importance in the terminal clinical
      phase of prion disease. The prion-induced pathology and lesion profile were
      similar between knockout mice and controls. The fragmentation pattern of protease
      resistant PrP as revealed in Western blots was also identical between the groups.
      Our data show that the fundamentals of prion propagation and pathological
      manifestation are not influenced by the oxidative DNA damage repair mechanisms
      studied here, but that progressive accumulation of oxidative lesions may
      accelerate the final toxic phase of prion disease. 

PMID- 24296245
TI  - Hypoxia-inducible factor 1 contributes to N-acetylcysteine's protection in
      stroke.
AB  - Stroke is a leading cause of adult morbidity and mortality with very limited
      treatment options. Evidence from preclinical models of ischemic stroke has
      demonstrated that the antioxidant N-acetylcysteine (NAC) effectively protects the
      brain from ischemic injury. Here, we evaluated a new pathway through which NAC
      exerted its neuroprotection in a transient cerebral ischemia animal model. Our
      results demonstrated that pretreatment with NAC increased protein levels of
      hypoxia-inducible factor-1alpha (HIF-1alpha), the regulatable subunit of HIF-1,
      and its target proteins erythropoietin (EPO) and glucose transporter (GLUT)-3, in
      the ipsilateral hemispheres of rodents subjected to 90min middle cerebral artery
      occlusion (MCAO) and 24h reperfusion. Interestingly, after NAC pretreatment and
      stroke, the contralateral hemisphere also demonstrated increased levels of HIF
      1alpha, EPO, and GLUT-3, but to a lesser extent. Suppressing HIF-1 activity with
      two widely used pharmacological inhibitors, YC-1 and 2ME2, and specific knockout
      of neuronal HIF-1alpha abolished NAC's neuroprotective effects. The results also
      showed that YC-1 and 2ME2 massively enlarged infarcts, indicating that their
      toxic effect was larger than just abolishing NAC's neuroprotective effects.
      Furthermore, we determined the mechanism of NAC-mediated HIF-1alpha induction. We
      observed that NAC pretreatment upregulated heat-shock protein 90 (Hsp90)
      expression and increased the interaction of Hsp90 with HIF-1alpha in ischemic
      brains. The enhanced association of Hsp90 with HIF-1alpha increased HIF-1alpha
      stability. Moreover, Hsp90 inhibition attenuated NAC-induced HIF-1alpha protein
      accumulation and diminished NAC-induced neuroprotection in the MCAO model. These
      results strongly indicate that HIF-1 plays an important role in NAC-mediated
      neuroprotection and provide a new molecular mechanism involved in the
      antioxidant's neuroprotection in ischemic stroke. 

PMID- 24296246
TI  - Molecular mechanisms of lipopolysaccharide-mediated inhibition of glutathione
      synthesis in mice.
AB  - Endotoxemia correlates with the degree of liver failure and may participate in
      worsening of liver diseases. Lipopolysaccharide (LPS; synonymous with endotoxin)
      treatment in mice lowered the hepatic glutathione (GSH) level, which in turn is a
      variable that determines susceptibility to LPS-induced injury. We previously
      showed that LPS treatment in mice lowered hepatic expression of the rate-limiting
      enzyme in GSH synthesis, glutamate-cysteine ligase (GCL). The aim of our current
      work was to determine the molecular mechanism(s) responsible for these changes.
      Studies were done using RAW cells (murine macrophages), in vivo LPS-treated mice,
      and mouse hepatocytes. We found that LPS treatment lowered GCL catalytic and
      modifier (Gclc and Gclm) subunit expression at the transcriptional level, which
      was unrelated to alterations in nitric oxide production or induction of NF
      kappaB/p65 subunit. The key mechanism was a decrease in sumoylation of nuclear
      factor-erythroid 2-related factor 2 (Nrf2) and MafG, which is required for their
      heterodimerization and subsequent binding and trans-activation of the antioxidant
      response element (ARE) present in the promoter region of these genes that is
      essential for their expression. LPS treatment lowered markedly the expression of
      ubiquitin-conjugating enzyme 9 (Ubc9), which is required for sumoylation. Similar
      findings also occurred in liver after in vivo LPS treatment and in LPS-treated
      mouse hepatocytes. Overexpression of Ubc9 protected against LPS-mediated
      inhibition of Gclc and Gclm expression in RAW cells and hepatocytes. In
      conclusion, LPS-mediated lowering of GCL expression in hepatocytes and
      macrophages is due to lowering of sumoylation of Nrf2 and MafG, leading to
      reduced heterodimerization, binding, and trans-activation of ARE. 

PMID- 24296247
TI  - Redox evaluation in sepsis model mice by the in vivo ESR technique using acyl
      protected hydroxylamine.
AB  - In vivo electron spin resonance (ESR) spectroscopy is a noninvasive technique
      that measures the oxidative stress in living experimental animals. The rate of
      decay of the ESR signal right after an injection of nitroxyl radical has been
      measured to evaluate the oxidative stress in animals, although the probe's
      disposition could also affect this rate. Because the amount of probes forming the
      redox pair of hydroxyl amine and its corresponding nitroxyl radical was shown to
      be nearly constant in most organs or tissues 10min after the injection of 1
      acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP) in mice, we evaluated
      the oxidative stress in sepsis model mice induced by lipopolysaccharide (LPS) by
      intravenously injecting ACP as a precursor of redox probes. The in vivo ESR
      signal increased up to 7-8min after the ACP injection and then decreased. Decay
      of the in vivo signal in LPS-treated mice was significantly slower than that in
      healthy mice, whereas no significant difference was observed in the rate of
      change in the total amount of redox probes in the blood and liver between these
      groups. ESR imaging showed that the in vivo signals observed at the chest and
      upper abdomen decayed slowly in LPS-treated mice. Suppression of the decay in LPS
      treated mice was canceled by the administration of a combination of pegylated
      superoxide dismutase and catalase, or an inhibitor of nitric oxide synthase, or
      gadolinium chloride. These results indicate that the LPS-treated mouse is under
      oxidative stress and that reactive oxygen species, such as superoxide and
      peroxynitrite, related to macrophages are mainly involved in the oxidative
      stress. 

PMID- 24296249
TI  - Microbe associated molecular patterns from rhizosphere bacteria trigger
      germination and Papaver somniferum metabolism under greenhouse conditions.
AB  - Ten PGPR from different backgrounds were assayed on Papaver somniferum var.
      Madrigal to evaluate their potential as biotic elicitors to increase alkaloid
      content under the rationale that some microbe associated molecular patterns
      (MAMPs) are able to trigger plant metabolism. First, the 10 strains and their
      culture media at two different concentrations were tested for their ability to
      trigger seed germination. Then, the best three strains were tested for their
      ability to increase seedling growth and alkaloid levels under greenhouse
      conditions. Only three strains and their culture media enhanced germination.
      Then, germination enhancing capacity of these best three strains, N5.18
      Stenotrophomonas maltophilia, Aur9 Chryseobacterium balustinum and N21.4
      Pseudomonas fluorescens was evaluated in soil. Finally, the three strains were
      applied on seedlings at two time points, by soil drench or by foliar spray.
      Photosynthesis was measured, plant height was recorded, capsules were weighted
      and alkaloids analyzed by HPLC. Only N5.18 delivered by foliar spray
      significantly increased plant height coupled to an increase in total alkaloids
      and a significant increase in opium poppy straw dry weight; these increases were
      supported by a better photosynthetic efficiency. The relative contents of
      morphine, thebaine, codeine and oripavine were affected by this treatment causing
      a significant increase in morphine coupled to a decrease in thebaine,
      demonstrating the effectivity of MAMPs from N5.18 in this plant species.
      Considering the increase in capsule biomass and alkaloids together with the
      acceleration of germination, strain N5.18 appears as a good candidate to elicit
      plant metabolism and consequently, to increase productivity of Papaver
      somniferum. 

PMID- 24296248
TI  - Renal improvement by zinc in diabetic mice is associated with glucose metabolism
      signaling mediated by metallothionein and Akt, but not Akt2.
AB  - Human epidemiological and animal studies have shown the beneficial effect of zinc
      supplementation on mitigating diabetic nephropathy. However, the mechanism by
      which zinc protects the kidney from diabetes remains unknown. Here we demonstrate
      the therapeutic effects of zinc on diabetes-induced renal pathological and
      functional changes. These abnormalities were found in both transgenic OVE26 and
      Akt2-KO diabetic mouse models, accompanied by significant changes in glucose
      metabolism-related regulators. The changes included significantly decreased
      phosphorylation of Akt and GSK-3beta, increased phosphorylation of renal glycogen
      synthase, decreased expression of hexokinase II and PGC-1alpha, and increased
      expression of the Akt negative regulators PTEN, PTP1B, and TRB3. All of these
      were significantly prevented by zinc treatment for 3 months. Furthermore, zinc
      stimulated changes in glucose metabolism mediated by Akt were actually found to
      be metallothionein dependent, but not Akt2 dependent. These results suggest that
      the therapeutic effects of zinc in diabetic nephropathy are mediated, in part, by
      the preservation of glucose-metabolism-related pathways via the prevention of
      diabetes-induced upregulation of Akt negative regulators. Given that zinc
      deficiency is very common in diabetics, this finding implies that regularly
      monitoring zinc levels in diabetic patients, as well as supplementing if low, is
      important in mitigating the development of diabetic nephropathy. 

PMID- 24296250
TI  - Perturbation of polyamine catabolism affects grape ripening of Vitis vinifera cv.
      Trincadeira.
AB  - Grapes are economically the most important fruit worldwide. However, the
      complexity of biological events that lead to ripening of nonclimacteric fruits is
      not fully understood, particularly the role of polyamines' catabolism. The
      transcriptional and metabolic profilings complemented with biochemical data were
      studied during ripening of Trincadeira grapes submitted to guazatine treatment, a
      potent inhibitor of polyamine oxidase activity. The mRNA expression profiles of
      one time point (EL 38) corresponding to harvest stage was compared between mock
      and guazatine treatments using Affymetrix GrapeGen((r)) genome array. A total of
      2113 probesets (1880 unigenes) were differentially expressed between these
      samples. Quantitative RT-PCR validated microarrays results being carried out for
      EL 35 (veraison berries), EL 36 (ripe berries) and EL 38 (harvest stage berries).
      Metabolic profiling using HPLC and (1)H NMR spectroscopy showed increase of
      putrescine, proline, threonine and 1-O-ethyl-beta-glucoside in guazatine treated
      samples. Genes involved in amino acid, carbohydrate and water transport were down
      regulated in guazatine treated samples suggesting that the strong dehydrated
      phenotype obtained in guazatine treated samples may be due to impaired transport
      mechanisms. Genes involved in terpenes' metabolism were differentially expressed
      between guazatine and mock treated samples. Altogether, results support an
      important role of polyamine catabolism in grape ripening namely in cell expansion
      and aroma development.

PMID- 24296251
TI  - High field structural MRI reveals specific episodic memory correlates in the
      subfields of the hippocampus.
AB  - The involvement of the hippocampus (HC) in episodic memory is well accepted;
      however it is unclear how each subfield within the HC contributes to memory
      function. Recent magnetic resonance imaging (MRI) studies suggest differential
      involvement of hippocampal subfields and subregions in episodic memory. However,
      most structural MRI studies have examined the HC subfields within a single
      subregion of the HC and used specialised experimental memory paradigms. The
      purpose of the present study was to determine the association between volumes of
      HC subfields throughout the entire HC structure and performance on standard
      neuropsychological memory tests in a young, healthy population. We recruited 34
      healthy participants under the age of 50. MRI data was acquired with a fast spin
      echo (FSE) sequence yielding a 0.52*0.68*1.0 mm(3) native resolution. The HC
      subfields - the cornu ammonis 1-3 (CA), dentate gyrus (DG), and subiculum (SUB) -
      were segmented manually within three hippocampal subregions using a previously
      defined protocol. Participants were administered the Wechsler Memory Scale, 4th
      edition (WMS-IV) to assess performance in episodic memory using verbal (Logical
      Memory, LM) and visual (Designs, DE; visual-spatial memory, DE-Spatial; visual
      content memory, DE-Content) memory subtests. Working memory subtests (Spatial
      Addition, SA; and Symbol Span, SSP) were included as well. Working memory was not
      associated with any HC volumes. Volumes of the DG were correlated with verbal
      memory (LM) and visual-spatial memory (DE-Spatial). Posterior CA volumes
      correlated with both visual-spatial and visual-object memory (DE-Spatial, DE
      Content). In general, anterior subregion volumes (HC head) correlated with verbal
      memory, while some anterior and many posterior HC subregion volumes (body and
      tail) correlated with visual memory scores (DE-Spatial, DE-Content). In addition,
      while verbal memory showed left-lateralized associations with HC volumes, visual
      memory was associated with HC volumes bilaterally. This the first study to
      examine the associations between hippocampal subfield volumes across the entire
      hippocampal formation with performance in a set of standard memory tasks.

PMID- 24296252
TI  - Crossmodal representation of a functional robotic hand arises after extensive
      training in healthy participants.
AB  - The way in which humans represent their own bodies is critical in guiding their
      interactions with the environment. To achieve successful body-space interactions,
      the body representation is strictly connected with that of the space immediately
      surrounding it through efficient visuo-tactile crossmodal integration. Such a
      body-space integrated representation is not fixed, but can be dynamically
      modulated by the use of external tools. Our study aims to explore the effect of
      using a complex tool, namely a functional prosthesis, on crossmodal visuo-tactile
      spatial interactions in healthy participants. By using the crossmodal visuo
      tactile congruency paradigm, we found that prolonged training with a mechanical
      hand capable of distal hand movements and providing sensory feedback induces a
      pattern of interference, which is not observed after a brief training, between
      visual stimuli close to the prosthesis and touches on the body. These results
      suggest that after extensive, but not short, training the functional prosthesis
      acquires a visuo-tactile crossmodal representation akin to real limbs. This
      finding adds to previous evidence for the embodiment of functional prostheses in
      amputees, and shows that their use may also improve the crossmodal combination of
      somatosensory feedback delivered by the prosthesis with visual stimuli in the
      space around it, thus effectively augmenting the patients' visuomotor abilities. 

PMID- 24296253
TI  - [Peripheral precocious puberty: 46, XY complete gonadal dysgenesis].
AB  - Despite standard clinical definitions and availability of diagnostic tests for
      precocious puberty, an intensive and structured investigation is needed in order
      to diagnose the aetiology in particular cases. A 4-year-old, phenotypically
      female child was referred to paediatric endocrinology consultation for premature
      pubarche and thelarche. There was an acceleration of growth velocity with high
      levels of estradiol and testosterone, and prepubertal FSH and LH measurements.
      Investigation showed bilateral gonadoblastoma as the cause of the peripheral
      precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89G>
      T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete
      gonadal dysgenesis. Disorders of sexual differentiation must be considered in the
      approach and investigation of peripheral precocious puberty, especially in the
      presence of ovarian tumours, such as gonadoblastoma and dysgerminoma. 

PMID- 24296254
TI  - Nerve growth factor stimulates regeneration of perivascular nerve, and induces
      the maturation of microvessels around the injured artery.
AB  - An immature vasa vasorum in the adventitia of arteries has been implicated in
      induction of the formation of unstable atherosclerotic plaques.
      Normalization/maturation of the vasa vasorum may be an attractive therapeutic
      approach for arteriosclerotic diseases. Nerve growth factor (NGF) is a pleotropic
      molecule with angiogenic activity in addition to neural growth effects. However,
      whether NGF affects the formation of microvessels in addition to innervation
      during pathological angiogenesis is unclear. In the present study, we show a new
      role for NGF in neovessels around injured arterial walls using a novel in vivo
      angiogenesis assay. The vasa vasorum around arterial walls was induced to grow
      using wire-mediated mouse femoral arterial injury. When collagen-coated tube
      (CCT) was placed beside the injured artery for 7-14 days, microvessels grew two
      dimensionally in a thin layer on the CCT (CCT-membrane) in accordance with the
      development of the vasa vasorum. The perivascular nerve was found at not only
      arterioles but also capillaries in the CCT-membrane. Biodegradable hydrogels
      containing VEGF and NGF were applied around the injured artery/CCT. VEGF
      significantly increased the total length and instability of microvessels within
      the CCT-membrane. In contrast, NGF induced regeneration of the peripheral nerve
      around the microvessels and induced the maturation and stabilization of
      microvessels. In an ex vivo nerve-free angiogenesis assay, although NGF
      potentially stimulated vascular sprouting from aorta tissues, no effects of NGF
      on vascular maturation were observed. These data demonstrated that NGF had potent
      angiogenic effects on the microvessels around the injured artery, and especially
      induced the maturation/stabilization of microvessels in accordance with the
      regeneration of perivascular nerves.

PMID- 24296255
TI  - The association between children's numerical magnitude processing and mental
      multi-digit subtraction.
AB  - Children apply various strategies to mentally solve multi-digit subtraction
      problems and the efficient use of some of them may depend more or less on
      numerical magnitude processing. For example, the indirect addition strategy
      (solving 72-67 as "how much do I have to add up to 67 to get 72?"), which is
      particularly efficient when the two given numbers are close to each other,
      requires to determine the proximity of these two numbers, a process that may
      depend on numerical magnitude processing. In the present study, children
      completed a numerical magnitude comparison task and a number line estimation
      task, both in a symbolic and nonsymbolic format, to measure their numerical
      magnitude processing. We administered a multi-digit subtraction task, in which
      half of the items were specifically designed to elicit indirect addition. Partial
      correlational analyses, controlling for intellectual ability and motor speed,
      revealed significant associations between numerical magnitude processing and
      mental multi-digit subtraction. Additional analyses indicated that numerical
      magnitude processing was particularly important for those items for which the use
      of indirect addition is expected to be most efficient. Although this association
      was observed for both symbolic and nonsymbolic tasks, the strongest associations
      were found for the symbolic format, and they seemed to be more prominent on
      numerical magnitude comparison than on number line estimation. 

PMID- 24296256
TI  - Impact of acid adaptation on attachment of Listeria monocytogenes to stainless
      steel during long-term incubation under low or moderate temperature conditions
      and on subsequent recalcitrance of attached cells to lethal acid treatments.
AB  - This study aimed to evaluate the possible impact of acid adaptation of Listeria
      monocytogenes cells on their attachment to stainless steel (SS) during long-term
      incubation under either low or moderate temperature conditions and on the
      subsequent recalcitrance of attached cells to lethal acid treatments. Initially,
      nonadapted or acid-adapted stationary phase L. monocytogenes cells were used to
      inoculate (ca. 108 CFU/ml) brain-heart infusion (BHI) broth in test tubes
      containing vertically placed SS coupons. Incubation was carried out at either 5
      or 30  degrees C for up to 15 days, under static conditions. On the 5th, 10th and
      15th days of incubation, attached cells were subjected to lethal acid treatments
      by exposing them, for either 6 or 60 min, to pH 2, adjusted with either
      hydrochloric or lactic acid. Following the acid treatments, remaining viable
      cells were detached (through strong vortexing with glass beads) and enumerated by
      agar plating, and also indirectly quantified by conductance measurements via
      their metabolic activity. Results obtained from both quantification techniques,
      employed here in parallel, revealed that although the numbers of attached cells
      for nonadapted and acid-adapted ones were similar, the latter were found to
      present significantly (p<0.05) increased recalcitrance to all the acid treatments
      for both incubation temperatures and all sampling days. In addition and
      regardless of acid adaptation, when long (60 min) acid treatments were applied,
      conductance measurements revealed that the weak organic lactic acid exhibited
      significantly (p<0.05) stronger antilisterial activity compared to the strong
      inorganic hydrochloric acid (at the same pH value of 2). To conclude, present
      results show that acid adaptation of L. monocytogenes cells during their
      planktonic growth is conserved even after 15 days of incubation under both low
      and moderate temperature conditions, and results in the increased recalcitrance
      of their sessile population to otherwise lethal acid treatments. This "stress
      hardening" should be severely taken into account when acidic decontamination
      interventions are used to kill attached to equipment surfaces cells of this
      important pathogenic bacterium.

PMID- 24296257
TI  - Escherichia coli with extended-spectrum beta-lactamases or transferable AmpC beta
      lactamases and Salmonella on meat imported into Sweden.
AB  - The presence of Enterobacteriaceae producing extended spectrum beta-lactamases
      (ESBL) or transferable AmpC beta-lactamases (pAmpC) is increasingly being
      reported in humans and animals world-wide. Their occurrence in food-producing
      animals suggests that meat is a possible link between the two populations. This
      study investigated the occurrence and characteristics of Salmonella and ESBL- or
      pAmpC-producing E. coli in 430 samples of beef, pork and broiler meat imported
      into Sweden, in order to provide data required for assessing the potential public
      health risk of these bacteria in food. Depending on region of origin, ESBL/pAmpC
      producing E. coli were found in 0-8% of beef samples, 2-13% of pork samples and
      15-95% of broiler meat samples. The highest prevalence was in South American
      broiler meat (95%), followed by broiler meat from Europe (excluding Denmark)
      (61%) and from Denmark (15%). Isolates from meat outside Scandinavia were
      generally defined as multiresistant. A majority of the ESBL/pAmpC genes were
      transferable by conjugation. Bla(CTX-M-2) and bla(CTX-M-8) were the dominant
      genes in E. coli from South American broiler meat, whereas bla(CMY-2) and bla(CTX
      M-1) dominated in European meat. The majority of bla(CMY-2) and bla(CTX-M-1) were
      situated on plasmids of replicon type incK and incI1, respectively. The same
      combinations of ESBL/pAmpC genes and plasmids have been described previously in
      clinical human isolates. Salmonella was found in five samples tested, from
      European pork and broiler meat. No Salmonella isolate was resistant to third
      generation cephalosporins. In conclusion, meat imported into Sweden, broiler meat
      in particular, is a potential source of human exposure to ESBL- and pAmpC
      producing E. coli.

PMID- 24296258
TI  - Dual-species biofilm formation by Escherichia coli O157:H7 and environmental
      bacteria isolated from fresh-cut processing facilities.
AB  - Biofilm formation is a mechanism adapted by many microorganisms that enhances the
      survival in stressful environments. In food processing facilities, foodborne
      bacterial pathogens, which many are poor biofilm formers, could potentially take
      advantage of this protective mechanism by interacting with other strong biofilm
      producers. The objective of this study was to determine the influence of bacteria
      native to fresh produce processing environments on the incorporation of
      Escherichia coli O157:H7 in biofilms. Bacteria strains representing 13 Gram
      negative species isolated from two fresh produce processing facilities in a
      previous study were tested for forming dual-species biofilms with E. coli
      O157:H7. Strong biofilm producing strains of Burkholderia caryophylli and
      Ralstonia insidiosa exhibited 180% and 63% increase in biofilm biomass, and
      significant thickening of the biofilms (B. caryophylli not tested), when co
      cultured with E. coli O157:H7. E. coli O157:H7 populations increased by
      approximately 1 log in dual-species biofilms formed with B. caryophylli or R.
      insidiosa. While only a subset of environmental isolates with strong biofilm
      formation abilities increased the presence of E. coli O157:H7 in biofilms, all
      tested E. coli O157:H7 exhibited higher incorporation in dual-species biofilms
      with R. insidiosa. These observations support the notion that E. coli O157:H7 and
      specific strong biofilm producing bacteria interact synergistically in biofilm
      formation, and suggest a route for increased survival potential of E. coli
      O157:H7 in fresh produce processing environments. 

PMID- 24296259
TI  - Relationships among hygiene indicators and enteric pathogens in irrigation water,
      soil and lettuce and the impact of climatic conditions on contamination in the
      lettuce primary production.
AB  - Eight Belgian lettuce farms located in the West Flanders were sampled to
      establish the relationships between levels of indicator bacteria, detection of
      enteric zoonotic pathogens and the temperature and precipitation during primary
      production. Pathogenic bacteria (PCR EHEC positives, Salmonella spp. or
      Campylobacter spp.) and indicator bacteria (total psychrotrophic aerobic plate
      count (TPAC), total coliforms, Escherichia coli, enterococci) were determined
      over a period of one and a half year from seedling leaves, peat-soil of the
      seedling, lettuce crops, field soil and irrigation water. Neither Salmonella
      isolates nor PCR EHEC signals were detected from lettuce although one out of 92
      field soil samples contained Salmonella spp. and five soil samples provided PCR
      positives for EHEC virulence factors (vt1 or vt2 and eae gene). A low prevalence
      of Campylobacter (8/88) was noted in lettuce. It was shown that irrigation water
      is a major risk factor with regard to the bacterial contamination of the fresh
      produce as the water samples showed on a regular basis E. coli presence (59.2% of
      samples>=1CFU/100ml) and occasionally detection of pathogens (25%, n=30/120), in
      particular Campylobacter spp. The highest correlations between indicator
      bacteria, pathogens, temperature and the amount of precipitation were observed
      for the water samples in contrast to the soil or lettuce samples where no
      correlations were observed. The high correlations between E. coli, total
      coliforms and enterococci in the water implicated redundancy between analyses.
      Presence of elevated levels of E. coli increased the probability for the presence
      of pathogens (Campylobacter spp., EHEC and Salmonella spp.), but had a low to
      moderate predictive value on the actual presence of pathogens. The presence of
      pathogens and indicator bacteria in the water samples showed a seasonal effect as
      they tend to be more present during the months with higher temperature. 

PMID- 24296260
TI  - Attenuated mitochondrial NADP+-dependent isocitrate dehydrogenase activity
      induces apoptosis and hypertrophy of H9c2 cardiomyocytes.
AB  - Oxidative stress, characterized by the accumulation of reactive oxygen species
      (ROS), is known to have numerous detrimental effects on the myocardium such as
      the induction of apoptotic cell death, hypertrophy, fibrosis, dysfunction, and
      dilatation. Over the past several years, we have shown that mitochondrial NADP(+)
      dependent isocitrate dehydrogenase (IDPm) functions as an antioxidant and anti
      apoptotic protein by supplying NADPH to antioxidant systems. Here, we showed that
      transfection of H9c2 clonal myoblastic cells with small interfering RNA (siRNA)
      specific for IDPm markedly attenuated IDPm expression and substantially induced
      apoptosis, senescence, and hypertrophy as indicated by increased atrial
      natriuretic peptide (ANP) gene expression, a marker of cardiomyocyte hypertrophy,
      and a larger cell size. Knockdown of IDPm expression resulted in the modulation
      of cellular and mitochondrial redox status, mitochondrial function, and cellular
      oxidative damage. Taken together, our results suggest that the suppression of
      IDPm expression by siRNA induces apoptosis and hypertrophy of cultured
      cardiomyocytes through the disruption of cellular redox balance. 

PMID- 24296262
TI  - Models and the mosaic of scientific knowledge. The case of immunology.
AB  - A survey of models in immunology is conducted and distinct kinds of models are
      characterized based on whether models are material or conceptual, the
      distinctiveness of their epistemic purpose, and the criteria for evaluating the
      goodness of a model relative to its intended purpose. I argue that the diversity
      of models in interdisciplinary fields such as immunology reflects the fact that
      information about the phenomena of interest is gathered from different sources
      using multiple methods of investigation. To each model is attached a description
      specifying how information about a phenomenon of interest has been acquired,
      highlighting points of commonality and difference between the methodological and
      epistemic histories of the information encapsulated in different models. These
      points of commonality and difference allow investigators to integrate findings
      from different models into more comprehensive explanatory accounts, as well as to
      troubleshoot anomalies and faulty accounts by going back to the original building
      blocks. 

PMID- 24296261
TI  - Sirtuin1 and autophagy protect cells from fluoride-induced cell stress.
AB  - Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent
      deacetylase functioning in the regulation of metabolism, cell survival and
      organismal lifespan. Active SIRT1 regulates autophagy during cell stress,
      including calorie restriction, endoplasmic reticulum (ER) stress and oxidative
      stress. Previously, we reported that fluoride induces ER-stress in ameloblasts
      responsible for enamel formation, suggesting that ER-stress plays a role in
      dental fluorosis. However, the molecular mechanism of how cells respond to
      fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride
      activates SIRT1 and initiates autophagy to protect cells from fluoride exposure.
      Fluoride treatment of ameloblast-derived cells (LS8) significantly increased
      Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation
      of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates
      autophagy, we characterized the expression of autophagy related genes (Atg);
      Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels
      were significantly increased following fluoride treatment. To confirm that SIRT1
      plays a protective role in fluoride toxicity, we used resveratrol (RES) to
      augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy,
      inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with
      fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly
      elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation
      stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were
      present in fluoride-treated rat maturation stage ameloblasts. Therefore, the
      SIRT1/autophagy pathway may play a critical role as a protective response to help
      prevent dental fluorosis.

PMID- 24296263
TI  - Childhood tinnitus: clinical characteristics and treatment.
AB  - PURPOSE: Troublesome tinnitus in children can have an impact on their lives
      leading to behavioral or psychological problems. The present study was designed
      to identify the clinical features of childhood tinnitus, to establish the
      treatment strategy for each tinnitus category and severity, and to assess the
      treatment outcomes. MATERIALS AND METHODS: Clinical data were retrospectively
      collected on 108 tinnitus patients in childhood and adolescence. The authors have
      classified tinnitus according to the acoustic source: otic (idiopathic
      subjective), myoclonic, and vascular tinnitus based on the tinnitus quality and
      appropriate diagnostic approaches. Treatment selection depended on the tinnitus
      category and severity. Treatment modalities included counseling, a simplified
      tinnitus retraining therapy, counseling with medications, and surgery. RESULTS:
      Of all 108 subjects, otic tinnitus was the most common form of childhood tinnitus
      (n=80) followed by myoclonic (n=21) and vascular tinnitus (n=6). The prevalence
      of otic tinnitus increased with age. The mean age of myoclonic tinnitus patients
      was younger than that of the others. The majority of otic tinnitus showed normal
      hearing. The origin of 81% of myoclonic tinnitus was middle ear muscles. Of all
      subjects, 67.6% had mild tinnitus responsive to counseling alone. Distressing
      tinnitus was most common in myoclonic tinnitus. Almost all patients (97%) who
      were followed up at 3 months (64%) showed improvements. CONCLUSIONS: We suggest
      that understanding the clinical characteristics of childhood tinnitus,
      establishing a diagnosis based on the acoustic source, and implementing
      appropriate therapy customized to the individual tinnitus category and severity
      would help clinicians to relieve tinnitus children of their troublesome tinnitus
      effectively.

PMID- 24296264
TI  - NPC1, intracellular cholesterol trafficking and atherosclerosis.
AB  - Post-lysosomal cholesterol trafficking is an important, but poorly understood
      process that is essential to maintain lipid homeostasis. Niemann-Pick type C1
      (NPC1), an integral membrane protein on the limiting membrane of late
      endosome/lysosome (LE/LY), is known to accept cholesterol from NPC2 and then
      mediate cholesterol transport from LE/LY to endoplasmic reticulum (ER) and plasma
      membrane in a vesicle- or oxysterol-binding protein (OSBP)-related protein 5
      (ORP5)-dependent manner. Mutations in the NPC1 gene can be found in the majority
      of NPC patients, who accumulate massive amounts of cholesterol and other lipids
      in the LE/LY due to a defect in intracellular lipid trafficking. Liver X receptor
      (LXR) is the major positive regulator of NPC1 expression. Atherosclerosis is the
      pathological basis of coronary heart disease, one of the major causes of death
      worldwide. NPC1 has been shown to play a critical role in the atherosclerotic
      progression. In this review, we have summarized the role of NPC1 in regulating
      intracellular cholesterol trafficking and atherosclerosis. 

PMID- 24296265
TI  - Selective, sensitive and fluorometric determination of urinary cytosine with 4
      trifluoromethylbenzamidoxime and N,N-dimethylformamide.
AB  - BACKGROUND: Cytosine in urine is one of the biomarkers for the diagnosis of
      metabolic immunodeficiency. It has been mentioned that a high level of cytosine
      is found in urine of children having immunodeficiency. In this study, we have
      developed a fluorescence (fluorescence) derivatization reaction of cytosine using
      4-trifluoromethylbenzamidoxime (4-TFMBAO) as a fluorogenic reagent. METHODS: In
      this reaction, cytosine was mixed with 4-TFMBAO, K3[Fe(CN)6], N,N
      dimethylformamide (DMF) and KOH in an aqueous solution. The mixture was heated at
      100 degrees C for 20 min. The fluorescence intensity of the mixture was measured
      with a spectrofluorometer. RESULTS: Under the optimized reaction conditions, a
      strong fluorescence was produced only from cytosine amongst 62 compounds
      including structurally related bio-substances. The selectivity and sensitivity of
      this method were compared with a conventional fluorescence one using 2
      bromoacetophenone that reacts with cytosine, adenine and their related
      substances. The present method was sufficiently selective toward cytosine, and
      approximately 50 times more sensitive than the conventional one. CONCLUSIONS: Our
      method permitted the quantitative determination of cytosine in human urines
      without any pretreatment for a primary screening test of inborn disorder in
      pyrimidine metabolism with immunodeficiency, and indicated the lower detection
      limit of 0.1 MUmol/l cytosine which gave 3 times greater fluorescence intensity
      than that observed for the reagent blank.

PMID- 24296266
TI  - Urine-based human papillomavirus DNA testing as a screening tool for cervical
      cancer in high-risk women.
AB  - OBJECTIVE: To test the hypothesis that self-collected urine could be used to
      detect high-risk human papillomavirus (HPV) DNA with sensitivity and specificity
      comparable to those of standard cervical testing. METHODS: Women attending a
      gynecology clinic for evaluation of abnormal cytology were recruited. Fifty-two
      participants (21-60years of age) collected urine samples, and clinicians
      collected cervical brush samples. When appropriate, cervical biopsies were
      obtained during colposcopy. HPV detection and typing were performed on DNA
      extracts from each sample, using commercial reagents for L1 consensus polymerase
      chain reaction (PCR) and type-specific hybridization. HPV 16 viral load was
      determined by quantitative PCR in HPV 16-positive samples. A diagnostic test
      analysis was conducted for urine samples. RESULTS: Fifty paired samples were
      analyzed, with 76% agreement between samples. The 12 discrepant pairs were all
      urine negative/cervix positive. The most common HPV types detected were 16, 51,
      53, and 62. The urine test correctly identified 100% of the uninfected and 65% of
      the infected patients. CONCLUSION: The results indicate that HPV DNA detection
      using urine is less sensitive than cervical sampling in a population with
      abnormal cytology. Further exploration is warranted to determine clinical utility
      when other options are unavailable.

PMID- 24296267
TI  - Molecular mechanism of polypeptides from Chlamys farreri (PCF)'s anti-apoptotic
      effect in UVA-exposed HaCaT cells involves HSF1/HSP70, JNK, XO, iNOS and NO/ROS.
AB  - This study investigated the molecular mechanisms of polypeptides from Chlamys
      farreri (PCF)'s anti-apoptotic effects in ultraviolet A-rays (UVA) exposed HaCaT
      cells. UVA-induced apoptosis in HaCaT cells was confirmed with Hoechst 33258
      fluorescent staining; PCF treatment inhibited UVA-induced apoptosis in HaCaT
      cells, increased transcriptional activities of heat shock factor protein 1 (HSF1)
      and the expression of heat shock protein 70 (HSP70), whereas inhibited activation
      of c-Jun N-terminal kinases (JNK), expression of xanthine oxidese (XO), inducible
      nitric oxide synthase (iNOS) and release of nitric oxide (NO)/reactive oxygen
      species (ROS). Meanwhile, the HSF1 transcription inhibitor quercetin increased
      UVA-induced apoptosis, activation of JNK, expression of XO and iNOS and release
      of NO/ROS. Among the two NO release peaks we found in UVA exposed HaCaT cells, XO
      inhibitor oxypurinol was found to be able to inhibit NO release at 3h post UVA
      exposure but not 18h, while iNOS inhibitor S-methylisothiourea sulfate (SMT) was
      found to inhibit iNOS expression and NO release at 18h but not 3h. PCF's
      protection against UVA-induced apoptosis in HaCaT cells involves increased
      transcriptional activity of HSF1, increased expression of HSP70, and the
      subsequential inhibition of JNK pathway, XO and iNOS expression and ROS/NO
      release. 

PMID- 24296268
TI  - Systematic review of the value of ultrasound and magnetic resonance
      musculoskeletal imaging in the evaluation of response to treatment of gout.
AB  - BACKGROUND: Imaging may be useful for monitoring response to therapy. Within the
      OMERACT proposal for the core set domains for outcome measures in chronic gout,
      serum urate levels, recurrence of gouty flares, tophus regression, and joint
      damage imaging have been included, among other proposed issues. OBJECTIVES: To
      perform a systematic literature review of the usefulness of magnetic resonance
      imaging (MRI) and ultrasound (US) on assessment of treatment response in patients
      with gout. METHODS: MEDLINE, EMBASE, Cochrane Library (up to February 2012), and
      abstracts presented at the 2010 and 2011 meetings of the American College of
      Rheumatology and European League Against Rheumatism, were searched for treatment
      studies of any duration and therapeutic options, examining the ability of MRI/US
      to assess treatment response in gouty patients. Meta-analyses, systematic
      reviews, randomized clinical trials, cohort and case-control studies and
      validation studies were included. Quality was appraised using validated scales.
      RESULTS: There were only 3 US published studies in the literature that analysed
      US utility on assessment of response to treatment in patients with gout. All of
      them were prospective case studies with a small number of patients and they were
      reviewed in detailed. A total of 36 patients with gout were examined with US. All
      of them had a baseline serum urate >6mg/dL. US features of gout (double contour
      sign, hyperechoic spots in synovial fluid, hyperechoic cloudy areas, tophus
      diameter and volume) achieved significant reduction in patients who reached the
      objective of uricemia <=6mg/dL in all the studies; however, patients in whom
      levels did not drop below 6mg/dL had no change of US features of gout. Other
      parameters evaluated in one study included ESR, CRP, number of tender joints
      (TRN), number of swollen joints, and pain score (SP). All of them decreased with
      uricemia reduction, but only TRN and SP were statistically significant. No data
      was found on the value of MRI on treatment response assessment in patients with
      gout. CONCLUSIONS: The improvement in ultrasound features shows concurrent
      validity with uric acid reduction. According to the published evidence, US can be
      a useful tool for monitoring treatment of gouty patients, although more research
      is needed. The value of MRI on treatment response assessment in patients with
      gout remains to be determined.

PMID- 24296269
TI  - Neonatal lupus erythematosis: a five-year case review.
AB  - Neonatal lupus erythematosus is an infrequent disease seen in newborns. It is
      caused by transplacental maternal autoantibody passage. Cutaneous involvement and
      congenital heart block (CHB) are the most common affections, although it may
      involve multiple organs like the liver, lungs, blood, nervous or digestive
      systems. This article present a review of the four cases diagnosed in the past
      five years in a Neonatal Unit, which shows the different clinical spectrum which
      can develop around this disease (CHB, multisystemic affection and two cutaneous
      cases), different autoantibodies (specially anti-SSA) with an early
      negativization during the first year of life and the possibility of future
      collagen vascular disease as occurred in one case. 

PMID- 24296270
TI  - Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute
      promyelocytic leukemia patients.
AB  - Limited information is available on the relationship between expression of some
      additional aberrant phenotypic features and outcome of acute promyelocytic
      leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and
      CD56 expression, and their prognostic value in a large series of APL patients.
      One hundred and fourteen adult patients consecutively diagnosed with PML/RARalpha
      positive APL and homogeneously treated with the AIDA induction schedule at a
      single institution were included in the study. Twelve (10.5%) and 9 (8%) of the
      114 patients expressed CD15 and CD56, respectively. CD15 expression identified a
      subset of patients with a classic morphologic subtype (92%), a prevalent
      association with a bcr1 expression (67%) with an unexpectedly higher frequency of
      relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival
      (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56
      expression was detected only in patients with a classic morphologic subtype, a
      prevalent bcr3 expression (67%), high incidence of differentiation syndrome
      (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04)
      and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the
      negative prognostic value of CD56 and we show that the same applies also to cases
      expressing CD15. These aberrant markers may be considered for the refinement of
      risk-adapted therapeutic strategies in APL patients. 

PMID- 24296271
TI  - Implementing smart pump technology in a pediatric intensive care unit: a cost
      effective approach.
AB  - OBJECTIVE: To analyze the cost effectiveness of implementing smart infusion pump
      technology in a pediatric intensive care unit (PICU). MATERIAL AND METHODS: An
      observational, prospective, intervention study with analytical components was
      carried out. A drug library was developed and integrated into the Carefusion
      Alaris Guardrails(r) infusion systems. A systematic analysis of all the data
      stored on the devices during use was performed by the data processing program
      Guardrails(r) CQI v4.1 Event Reporter. Intercepted errors were classified in
      terms of their potential severity and probability of causing an adverse effect
      (PAE) had they reached the patient. Knowing the estimated cost of a preventable
      adverse effect (AE), we analyzed costs saved and the profit/cost ratio resulting
      from the implementation process. RESULTS: Compliance with the drug library was
      92% and during the study period 92 infusion-related programming errors were
      intercepted, leading to a saving of 172,279 euros by preventing AEs. This means
      that 2.15 euros would be obtained for each euro invested in hiring a pharmacist
      to implement this technology. DISCUSSION: The high percentage of use of safety
      software in our study compared to others allowed for the interception of 92
      errors. The estimation of the potential impact of these errors is based on
      clinical judgment. The cost saved might be underestimated because the cost of an
      AE is usually higher in pediatrics, indirect and intangible costs were not
      considered and pharmacists involved do not spend the whole day on this task.
      CONCLUSIONS: Smart pumps have shown to be profitable in a PICU because they have
      the ability to intercept potentially serious medication errors and reduce costs
      associated with such errors.

PMID- 24296272
TI  - Tandem mass spectrometric characterization of bile acids and steroid conjugates
      based on low-energy collision-induced dissociation.
AB  - We examined the characteristics of several bile acids and some steroid conjugates
      under low-energy-collision-induced dissociation conditions using a triple
      quadrupole tandem mass spectrometer. According to conjugation types, we observed
      characteristic product ions and/or neutral losses in the product ion spectra.
      Amino acid conjugates afforded specific product ions. For example, glycine
      conjugated metabolites routinely produced a product ion at m/z 74, and taurine
      conjugated metabolites produced product ions at m/z 124, 107, and 80. When a
      strong peak appeared at m/z 97, the molecule contained a sulfate group. In
      contrast to amino acid conjugates, carbohydrate conjugates required a combination
      of product ions and neutral losses for identification. We could discriminate a
      glucoside from an acyl galactoside according to the presence or absence of a
      product ion at m/z 161 and a neutral loss of 180 Da. Discrimination among esters,
      aliphatic ethers, and phenolic ether types of glucuronides was based upon
      differences in the intensities of a product ion at m/z 175 and a neutral loss of
      176 Da. Furthermore, N-acetylglucosamine conjugates showed a characteristic
      product ion at m/z 202 and a neutral loss of 203 Da, and the appearance of a
      product ion at m/z 202 revealed the existence of N-acetylglucosamine conjugated
      to an aliphatic hydroxyl group without a double bond in the immediate vicinity.
      Together, the data presented here will help to enable the identification of
      unknown conjugated cholesterol metabolites by using low-energy collision-induced
      dissociation.

PMID- 24296273
TI  - Depressive symptoms and regional cerebral blood flow in Alzheimer's disease.
AB  - Depressive symptoms are common in patients with Alzheimer's disease (AD) and
      increase the caregiver burden, although the etiology and pathologic mechanism of
      depressive symptoms in AD patients remain unclear. In this study, we tried to
      clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD,
      excluding the effect of apathy and anxiety. Seventy-nine consecutive patients
      with AD were recruited from outpatient units of the Memory Clinic of Okayama
      University Hospital. The level of depressive symptoms was evaluated using the
      depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent
      brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age,
      anxiety and apathy scores of NPI, and five subscales of Addenbrooke's Cognitive
      Examination-revised (ACE-R), correlation analysis of NPI depression scores showed
      a significant cluster of voxels in the left middle frontal gyrus (Brodmann area
      9), similar to the areas in the simple correlation analysis. The dorsolateral
      prefrontal area is significantly involved in the pathogenesis of depressive
      symptoms in AD, and the area on the left side especially may be closely related
      to the depressive symptoms revealed by NPI. 

PMID- 24296274
TI  - A model for influences on reliable and valid health care-associated infection
      data.
AB  - Reliable surveillance data and continuous monitoring can provide useful
      information for clinicians and patients alike, by identifying areas needing
      improvement and demonstrating the effectiveness of interventions. Improving the
      rigor of health care-associated infection surveillance makes it possible to
      provide more valid and reliable information. We propose a model that can be used
      by infection control preventionists, researchers, and health planners and can
      serve as a trigger for understanding the influences on reliable and valid health
      care-associated infection data. 

PMID- 24296275
TI  - Dynamic contact mechanics on the tibial plateau of the human knee during
      activities of daily living.
AB  - Despite significant advances in scaffold design, manufacture, and development, it
      remains unclear what forces these scaffolds must withstand when implanted into
      the heavily loaded environment of the knee joint. The objective of this study was
      to fully quantify the dynamic contact mechanics across the tibial plateau of the
      human knee joint during gait and stair climbing. Our model consisted of a
      modified Stanmore knee simulator (to apply multi-directional dynamic forces), a
      two-camera motion capture system (to record joint kinematics), an electronic
      sensor (to record contact stresses on the tibial plateau), and a suite of post
      processing algorithms. During gait, peak contact stresses on the medial plateau
      occurred in areas of cartilage-cartilage contact; while during stair climb, peak
      contact stresses were located in the posterior aspect of the plateau, under the
      meniscus. On the lateral plateau, during gait and in early stair-climb, peak
      contact stresses occurred under the meniscus, while in late stair-climb, peak
      contact stresses were experienced in the zone of cartilage-cartilage contact. At
      45% of the gait cycle, and 20% and 48% of the stair-climb cycle, peak stresses
      were simultaneously experienced on both the medial and lateral compartment,
      suggesting that these phases of loading warrant particular consideration in any
      simulation intended to evaluate scaffold performance. Our study suggests that in
      order to design a scaffold capable of restoring 'normal' contact mechanics to the
      injured knees, the mechanics of the intended site of implantation should be taken
      into account in any pre-clinical testing regime. 

PMID- 24296277
TI  - Epileptic seizure prediction using phase synchronization based on bivariate
      empirical mode decomposition.
AB  - OBJECTIVE: Epilepsy is a common neurological disorder with unpredictability. An
      effective algorithm for seizure prediction is important for the patients with
      refractory epilepsy. METHODS: We proposed a seizure prediction method based on
      the phase synchronization information of neuronal electrical activities. Firstly,
      the instantaneous phase of the intracranial electroencephalograph (EEG)
      recordings was detected by the combination of bivariate empirical mode
      decomposition (BEMD) and Hilbert transformation. Then, the phase information was
      used to calculate the mean phase coherence (MPC) as a measure of phase coupling
      strength between different channels of EEG recordings. In the end, the preictal
      changes of MPC time courses were used to raise the seizure alarms. We compared
      the proposed method with other existing methods to further investigate its
      effectiveness. RESULTS: Both the increase and the decrease of phase
      synchronization were found prior to seizure onset. Our results indicated that the
      proposed method had the best performance among three predictors. CONCLUSIONS: The
      proposed algorithm can effectively extract the phase synchrony changes prior to
      the seizure onset and contribute to the application of the seizure prediction.
      SIGNIFICANCE: Phase synchronization analysis based on the BEMD method may be a
      useful algorithm for clinical application in epileptic prediction.

PMID- 24296276
TI  - Mechanical stiffness as an improved single-cell indicator of osteoblastic human
      mesenchymal stem cell differentiation.
AB  - Although it has been established that cellular stiffness can change as a stem
      cell differentiates, the precise relationship between cell mechanics and other
      phenotypic properties remains unclear. Inherent cell heterogeneity and
      asynchronous differentiation complicate population analysis; therefore, single
      cell analysis was employed to determine how changes in cell stiffness correlate
      with changes in molecular biomarkers during differentiation. Design of a custom
      gridded tissue culture dish facilitated single-cell comparisons between cell
      mechanics and other differentiation biomarkers by enabling sequential measurement
      of cell mechanics and protein biomarker expression at the single cell level. The
      Young's modulus of mesenchymal stem cells was shown not only to decrease during
      chemically-induced osteoblast differentiation, but also to correlate more closely
      with the day of differentiation than did the relative expression of the
      traditional osteoblast differentiation markers, bone sialoprotein and
      osteocalcin. Therefore, cell stiffness, a measurable property of individual
      cells, may serve as an improved indicator of single-cell osteoblast
      differentiation compared to traditional biological markers. Revelation of
      additional osteoblast differentiation indicators, such as cell stiffness, can
      improve identification and collection of starting cell populations, with
      applications to mesenchymal stem cell therapies and stem cell-based tissue
      engineering. 

PMID- 24296278
TI  - Reliability of SFEMG in diagnosing myasthenia gravis: sensitivity and specificity
      calculated on 100 prospective cases.
AB  - OBJECTIVE: The study aimed to determine the utility of single-fibre
      electromyography (SFEMG) in the diagnosis of myasthenia gravis (MG) in subjects
      with a clinical suspicion of the disease. METHODS: We performed a prospective,
      single-blinded study on 100 consecutive patients. SFEMG was not considered a
      criterion in making the MG diagnosis. For all cases, a different physician than
      the one performing SFEMG made the diagnosis of MG. All subjects underwent
      standard SFEMG of a single muscle, the orbicularis oculi. RESULTS: SFEMG was
      abnormal in 67 of 100 patients. A final diagnosis of definite MG was made in 54
      patients (30 men/24 women). SFEMG was positive in 53 of 54 patients diagnosed
      with MG. The sensitivity of SFEMG in diagnosing MG was 98% (95% CI: 0.94-1.02),
      while the specificity was 70% (95% CI: 0.54-0.86), with a positive predictive
      value of 79% (95% CI: 0.74-0.79) and a negative predictive value of 97% (95% CI:
      0.94-0.99). CONCLUSIONS: In this cohort of patients, normal SFEMG findings were
      unlikely to occur in patients with MG. SIGNIFICANCE: SFEMG is not a confirmatory
      test for the diagnosis of MG, but it has a high negative predictive value in
      identifying patients without MG.

PMID- 24296279
TI  - Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of
      endothelial nitric oxide synthase and vascular dysfunction in aging.
AB  - Recently, we demonstrated that gene ablation of mitochondrial manganese
      superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age
      related vascular dysfunction and mitochondrial oxidative stress. The present
      study has sought to investigate the extent of vascular dysfunction and oxidant
      formation in glutathione peroxidase-1-deficient (GPx-1(-/-)) mice during the
      aging process with special emphasis on dysregulation (uncoupling) of the
      endothelial NO synthase. GPx-1(-/-) mice on a C57 black 6 (C57BL/6) background at
      2, 6, and 12 months of age were used. Vascular function was significantly
      impaired in 12-month-old GPx-1(-/-) -mice as compared with age-matched controls.
      Oxidant formation, detected by 3-nitrotyrosine staining and dihydroethidine-based
      fluorescence microtopography, was increased in the aged GPx-1(-/-) mice. Aging
      per se caused a substantial protein kinase C- and protein tyrosine kinase
      dependent phosphorylation as well as S-glutathionylation of endothelial NO
      synthase associated with uncoupling, a phenomenon that was more pronounced in
      aged GPx-1(-/-) mice. GPx-1 ablation increased adhesion of leukocytes to cultured
      endothelial cells and CD68 and F4/80 staining in cardiac tissue. Aged GPx-1(-/-)
      mice displayed increased oxidant formation as compared with their wild-type
      littermates, triggering redox-signaling pathways associated with endothelial NO
      synthase dysfunction and uncoupling. Thus, our data demonstrate that aging leads
      to decreased NO bioavailability because of endothelial NO synthase dysfunction
      and uncoupling of the enzyme leading to endothelial dysfunction, vascular
      remodeling, and promotion of adhesion and infiltration of leukocytes into
      cardiovascular tissue, all of which was more prominent in aged GPx-1(-/-) mice. 

PMID- 24296281
TI  - Temporal evolution of cognitive changes in incident hypertension: prospective
      cohort study across the adult age span.
AB  - Midlife hypertension is a risk factor for dementia, but little is known about the
      cognitive trajectories of individuals with incident hypertension. This study
      follows the cognitive functioning in prevalent and incident hypertension for 12
      years and in relation to age and treatment status. Cognitively intact adults aged
      25 to 84 years (n=1805) were serially assessed at baseline, 6 years, and 12
      years. Hypertension was defined by sphygmomanometry or antihypertensive
      medication use, and its association with cognitive decline was tested in random
      effects models. At baseline, 638 (35.3%) participants had hypertension. They
      showed faster decline in memory (chi(2) test for homogeneity=35.75; df=2;
      P<0.001), executive functions (chi(2)=21.68; df=2; P<0.001), and information
      processing speed (chi(2)=81.96; df= 2; P<0.001) than baseline normotensive
      participants. At follow-up, 352 individuals (30.2%) developed incident
      hypertension. They showed faster decline in memory (chi(2)=7.88; df=2; P=0.019)
      and information processing speed (chi(2)= 18.06; df=2; P<0.001), especially from
      6- to 12-year follow-up. Effects were most pronounced and widespread in midlife
      for both prevalent and incident hypertension and in those with untreated and
      uncontrolled hypertension. This study shows that incident hypertension predicts
      cognitive decline in middle-aged individuals, and those with poorly controlled
      blood pressure are most at risk. In newly diagnosed individuals, decline evolves
      gradually, possibly opening a window for early intervention. 

PMID- 24296280
TI  - Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt
      to induce vascular stiffness.
AB  - Arterial stiffness is recognized as a risk factor for many cardiovascular
      diseases. Aldosterone via its binding to and activation of the mineralocorticoid
      receptors (MRs) is a main regulator of blood pressure by controlling renal sodium
      reabsorption. Although both clinical and experimental data indicate that MR
      activation by aldosterone is involved in arterial stiffening, the molecular
      mechanism is not known. In addition to the kidney, MR is expressed in both
      endothelial and vascular smooth muscle cells (VSMCs), but the specific
      contribution of the VSMC MR to aldosterone-induced vascular stiffness remains to
      be explored. To address this question, we generated a mouse model with
      conditional inactivation of the MR in VSMC (MR(SMKO)). MR(SMKO) mice show no
      alteration in renal sodium handling or vascular structure, but they have
      decreased blood pressure when compared with control littermate mice. In vivo at
      baseline, large vessels of mutant mice presented with normal elastic properties,
      whereas carotids displayed a smaller diameter when compared with those of the
      control group. As expected after aldosterone/salt challenge, the arterial
      stiffness increased in control mice; however, it remained unchanged in MR(SMKO)
      mice, without significant modification in vascular collagen/elastin ratio.
      Instead, we found that the fibronectin/alpha5-subunit integrin ratio is
      profoundly altered in MR(SMKO) mice because the induction of alpha5 expression by
      aldosterone/salt challenge is prevented in mice lacking VSMC MR. Altogether, our
      data reveal in the aldosterone/salt hypertension model that MR activation
      specifically in VSMC leads to the arterial stiffening by modulation of cell
      matrix attachment proteins independent of major vascular structural changes. 

PMID- 24296282
TI  - Normotensive blood pressure in pregnancy: the role of salt and aldosterone.
AB  - A successful pregnancy requires an accommodating environment. Salt and water
      availability are critical for plasma volume expansion. Any changes in sodium
      intake would alter aldosterone, a hormone previously described beneficial in
      pregnancy. To date, it remains ambiguous whether high aldosterone or high salt
      intake is preferable. We hypothesized that increased aldosterone is a rescue
      mechanism and appropriate salt availability is equally effective in maintaining a
      normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive
      pregnant women (n=31) throughout pregnancy with young healthy female individuals
      (n=31-62) and performed salt sensitivity testing within the first trimester.
      Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured
      by gas chromatography-mass spectrometry and urinary sodium excretion corrected
      for creatinine, respectively, was shifted toward a higher salt intake in
      pregnancy (P<0.0001). In pregnancy, neither high urinary tetrahydro-aldosterone
      nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant
      women, systolic BP rose with aldosterone (P<0.05). Testing the impact of salt on
      BP, we performed salt sensitivity testing in a final cohort of 19 pregnant and 24
      nonpregnant women. On salt loading, 24-hour mean arterial pressure rose by 3.6+/
      1.5 and dropped by -2.8+/-1.5 mm Hg favoring pregnant women (P<0.01; chi(2)=6.04;
      P<0.02). Our data suggest first that salt responsiveness of aldosterone is
      alleviated in conditions of pregnancy without causing aldosterone-induced
      hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons
      incompletely elucidated, yet involving renin suppression and potentially
      placental sensing mechanisms. Further research should identify susceptible
      individuals and clarify effector mechanisms. 

PMID- 24296283
TI  - Mineralocorticoid receptor, the main player in aldosterone-induced large artery
      stiffness.

PMID- 24296284
TI  - Childhood family living arrangements and blood pressure in black men: the Howard
      University Family Study.
AB  - Black men have higher blood pressure (BP) levels and consequently higher
      prevalence of hypertension compared with men from other ethnic groups in the
      United States. Socio-familial factors in childhood have been found to play an
      important role in hypertension, but few studies have examined this relationship
      among black men. We investigated whether childhood family living arrangements are
      independently associated with mean BP and hypertension in a cross-sectional
      sample of 515 unrelated black male participants aged >=20 years enrolled in the
      Howard University Family Study between 2001 and 2008. Black men who lived with
      both parents compared with the reference group of men who never lived with both
      parents during their lifetime had lower systolic BP (-4.4 mm Hg [95% confidence
      interval {CI}, -7.84 to -0.96]), pulse pressure (-3.9 mm Hg [95% CI, -6.28 to 
      1.51]), and mean arterial BP (-2.0 mm Hg [95% CI, -4.44 to 0.51]). This
      protective effect was more pronounced among men who lived with both parents for 1
      to 12 years of their lives; they had decreased systolic BP (-6.5 mm Hg [95% CI, 
      10.99 to -1.95]), pulse pressure (-5.4 mm Hg [95% CI, -8.48 to -2.28]), mean
      arterial pressure (-3.3 mm Hg [95% CI, -6.56 to 0.00]), and a 46% decreased odds
      of developing hypertension (odds ratio=0.54; 95% CI, 0.30 to 0.99). No
      statistically significant associations were found for diastolic BP. These results
      provide preliminary evidence that childhood family structure exerts a long-term
      influence on BP among black men. 

PMID- 24296285
TI  - Zinc oxide nanoparticles delay soybean development: a standard soil microcosm
      study.
AB  - Soybean is an important crop and a source of food for humans and livestock. In
      this study, for the first time, the long-term effects of zinc oxide (ZnO)
      nanoparticles on the growth, development, and reproduction of soybean [Glycine
      max (L.) Merrill] were evaluated in a standard soil microcosm study. The soil was
      treated with 0, 50, or 500 mg/kg (dry weight) of ZnO nanoparticles. The growth
      and development of soybean plants were tracked during a cultivation period of 8-9
      weeks under greenhouse conditions. Soybean development was damaged in both
      treatment groups, particularly in the group that received 500 mg/kg ZnO
      nanoparticles. In comparison with the control group, the roots and shoots of
      soybeans in treatment groups were shorter and had smaller surface area and
      volume. Furthermore, the plants in the 500 mg/kg treatment group did not form
      seeds. ZnO nanoparticles negatively affected the developmental stages and
      reproduction of soybean plants in a soil microcosm.

PMID- 24296286
TI  - Cognitively inspired reinforcement learning architecture and its application to
      giant-swing motion control.
AB  - Many algorithms and methods in artificial intelligence or machine learning were
      inspired by human cognition. As a mechanism to handle the exploration
      exploitation dilemma in reinforcement learning, the loosely symmetric (LS) value
      function that models causal intuition of humans was proposed (Shinohara et al.,
      2007). While LS shows the highest correlation with causal induction by humans, it
      has been reported that it effectively works in multi-armed bandit problems that
      form the simplest class of tasks representing the dilemma. However, the scope of
      application of LS was limited to the reinforcement learning problems that have K
      actions with only one state (K-armed bandit problems). This study proposes LS-Q
      learning architecture that can deal with general reinforcement learning tasks
      with multiple states and delayed reward. We tested the learning performance of
      the new architecture in giant-swing robot motion learning, where uncertainty and
      unknown-ness of the environment is huge. In the test, the help of ready-made
      internal models or functional approximation of the state space were not given.
      The simulations showed that while the ordinary Q-learning agent does not reach
      giant-swing motion because of stagnant loops (local optima with low rewards), LS
      Q escapes such loops and acquires giant-swing. It is confirmed that the smaller
      number of states is, in other words, the more coarse-grained the division of
      states and the more incomplete the state observation is, the better LS-Q performs
      in comparison with Q-learning. We also showed that the high performance of LS-Q
      depends comparatively little on parameter tuning and learning time. This suggests
      that the proposed method inspired by human cognition works adaptively in real
      environments. 

PMID- 24296287
TI  - Intra-familiar discordant PKU phenotype explained by mutation analysis in three
      pedigrees.
AB  - Classical phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are two
      phenotypes of phenylalanine hydroxylase (PAH) deficiency with different degrees
      of severity. We have analyzed three families in which classical PKU, MHP and a
      normal phenotype occurred within each family due to the different combinations of
      three mutations segregating within the family. Indeed, sequence PAH analysis
      revealed three different alleles segregating in each family. This report suggests
      that when discordant phenotypes occur in a family, complete analysis of the PAH
      gene may be performed in order to support the diagnosis and assist in accurate
      genetic counseling and patient management. We further support the marked
      heterogeneity of hyperphenylalaninemia primarily due to allelic heterogeneity at
      the PAH locus. 

PMID- 24296291
TI  - Linear solvation energy relationships as classifier in non-target analysis--an
      approach for isocratic liquid chromatography.
AB  - Linear solvation energy relationship (LSER) models are developed to characterize
      various HPLC columns and to predict retention of candidate compounds in non
      target analysis of environmental samples. The models can be applied as classifier
      to exclude potential candidate structures with the same empirical formula. The
      application of the classifier was tested for a set of 19 isomers with empirical
      formula C12H10O2. The performance of the classifier was also demonstrated for a
      validation set of seven structural diverse compounds, where all potential
      candidates for the corresponding empirical formulas were included in the studies.
      Herein, the standard deviation of all compound descriptors of the respective
      candidate compounds was used as indication for potential exclusions on a certain
      column. 

PMID- 24296288
TI  - Development of a new biochemical test to diagnose and monitor neuroblastoma in
      Vietnam: homovanillic and vanillylmandelic acid by gas chromatography-mass
      spectrometry.
AB  - OBJECTIVES: The aim of this study was to develop an accurate robust testing
      method to simultaneously measure urine levels of HVA and VMA using gas
      chromatography mass spectrometry (GCMS) and to establish age-specific reference
      intervals of HVA and VMA in random urines for Vietnamese children. DESIGN AND
      METHODS: The assay for urinary HVA and VMA was developed based on a classical
      urinary organic acid profiling method. Briefly, this incorporated 3-phenyl
      butyric acid as the internal standard and liquid-liquid extraction with ethyl
      acetate followed by derivatization with BSTFA. The Agilent 7890A GC and 5975C
      Mass Selective Detector in single ion monitoring mode was used for analysis.
      Reference intervals were developed from random urine samples collected from 634
      disease free Vietnamese children and compared to 50 known neuroblastoma patient
      samples. Results were reported relative to creatinine concentration. Age related
      95% reference intervals for urinary HVA and VMA were estimated from sample
      quantiles. The analytes (expressed as analyte/creatinine ratios) diagnostic
      values were determined by calculating the related sensitivity, specificity and
      likelihood ratios. RESULTS: HVA and VMA were linear to at least 193 and
      221MUmol/L, respectively. The limit of quantitation for both analytes was
      0.9MUmol/L. Using the bi-level control (n=15), the within-batch coefficients of
      variations (CVs) were less than 3% for both analytes across the assay range. The
      between-batch CVs (n=20 over three months), were 3.6% at 11MUmol/L and 2.1% at
      88MUmol/L for HVA, 6.6% at 18.2MUmol/L and 2.6% at 90.6MUmol/L for VMA.
      Vietnamese age related reference intervals were established for urinary HVA and
      VMA per creatinine. HVA for children <6months (n=91) was 5.3-37.0MUmol/mmol;
      6months to <1year (n=141) was 2.7-27.7MUmol/mmol; 1 to 5years (n=139) was 3.4
      17.9MUmol/mmol; 6 to 10years (n=136) was 2.7-8.8MUmol/mmol; and 11 to 15years
      (n=127) was 1.1-9.4MUmol/mmol. VMA for children <6months was 1.8-12.2MUmol/mmol;
      6months to <1year was 1.5-9.3MUmol/mmol; 1 to 5years was 1.9-7.8MUmol/mmol; 6 to
      10years was 1.6-5.1MUmol/mmol; and 11 to 15years was <0.9-6.3MUmol/mmol.
      CONCLUSIONS: A robust testing method for simultaneous quantitation of urinary HVA
      and VMA by GCMS was developed. This method is accurate, precise and fit for its
      clinical purpose and suitable for developing countries. Age-related reference
      intervals of urinary HVA and VMA were established for Vietnamese children and the
      intervals declined progressively with increasing age for each analyte.

PMID- 24296292
TI  - Very high pressure liquid chromatography using fully porous particles:
      quantitative analysis of fast gradient separations without post-run times.
AB  - Using a column packed with fully porous particles, four methods for controlling
      the flow rates at which gradient elution runs are conducted in very high pressure
      liquid chromatography (VHPLC) were tested to determine whether reproducible
      thermal conditions could be achieved, such that subsequent analyses would proceed
      at nearly the same initial temperature. In VHPLC high flow rates are achieved,
      producing fast analyses but requiring high inlet pressures. The combination of
      high flow rates and high inlet pressures generates local heat, leading to
      temperature changes in the column. Usually in this case a post-run time is input
      into the analytical method to allow the return of the column temperature to its
      initial state. An alternative strategy involves operating the column without a
      post-run equilibration period and maintaining constant temperature variations for
      subsequent analysis after conducting one or a few separations to bring the column
      to a reproducible starting temperature. A liquid chromatography instrument
      equipped with a pressure controller was used to perform constant pressure and
      constant flow rate VHPLC separations. Six replicate gradient separations of a
      nine component mixture consisting of acetophenone, propiophenone, butyrophenone,
      valerophenone, hexanophenone, heptanophenone, octanophenone, benzophenone, and
      acetanilide dissolved in water/acetonitrile (65:35, v/v) were performed under
      various experimental conditions: constant flow rate, two sets of constant
      pressure, and constant pressure operation with a programmed flow rate. The
      relative standard deviations of the response factors for all the analytes are
      lower than 5% across the methods. Programming the flow rate to maintain a fairly
      constant pressure instead of using instrument controlled constant pressure
      improves the reproducibility of the retention times by a factor of 5, when
      plotting the chromatograms in time. 

PMID- 24296293
TI  - Comprehensive multi-channel multi-dimensional counter-current chromatography for
      separation of tanshinones from Salvia miltiorrhiza Bunge.
AB  - Multi-dimensional chromatography offers the increased resolution and peak
      capacity by coupling of multiple columns with the same or different separation
      mechanisms. In this work, a novel multi-channel multi-dimensional counter-current
      chromatography (CCC) has been successfully constructed and used for several two
      dimensional (2D) and three-dimensional (3D) CCC separations including 2D A*B/A*C,
      A*B-C and A-B*C, and 3D A*B*C systems. These 2D and 3D CCC systems were further
      applied to separate the bioactive tanshinones from the extract of Tanshen (or
      Danshen, Salvia miltiorrhiza Bunge), a famous Traditional Chinese Medicine (TCM).
      As a result, the developed 2D and 3D CCC methods were successful and efficient
      for resolving the tanshinones from complex extracts. Compared to the 1D multiple
      columns CCC separation, the 2D and 3D CCC decrease analysis time, reduce solvent
      consumption and increase sample throughput significantly. It may be widely used
      for current drug development, metabolomic analysis and natural product isolation.

PMID- 24296294
TI  - Spermine Sepharose as a clustered-charge anion exchange adsorbent.
AB  - We previously showed that the affinity and capacity of ion exchange adsorbents of
      a given total charge density are improved by immobilization of the charges in pre
      ordered clusters, rather than individually in random locations. This previous
      work used pentalysinamide and pentaargininamide as clustered ligands. This
      approach allows close control of cluster size, but is uneconomically expensive
      for some research and most practical applications. In this work, we demonstrate
      that the inexpensive synthetic analog of the natural polyamine spermine (H2N-CH2
      CH2-CH2-NH-CH2-CH2-CH2-CH2-NH-CH2-CH2-CH2-NH2) also can serve as the basis of
      effective clustered adsorbents. The calcium-depleted form of the protein alpha
      lactalbumin, and RNA from baker's yeast, were adsorbed on a spermine Sepharose
      adsorbent. This adsorbent exhibited enhanced alpha-lactalbumin binding capacity
      (Qmax>1.6 and 1.3-fold higher than those for Qiagen DEAE and GE DEAE Sepharose
      adsorbents of much greater charge density) and higher initial binding affinity
      (Qmax/KD 2.4 and 2.1-fold higher, respectively). The new spermine-based matrix
      exhibited a higher value of the Z parameter, suggesting an increased number of
      apparent interaction sites between the protein and the resin, and functioned well
      in column mode.

PMID- 24296295
TI  - Development of chromatofocusing techniques employing mixed-mode column packings
      for protein separations.
AB  - Recent studies reported in the literature using mixed-mode chromatography (MMC)
      column packings have shown that multiple modes of interactions between the column
      packing and proteins can be usefully exploited to yield excellent resolution as
      well as salt-tolerant adsorption of the target protein. In this study, a mixed
      mode separation method using commercially available column packings was explored
      which combines the techniques of hydrophobic-interaction chromatography and
      chromatofocusing. Two different column packings, one based on mercapto-ethyl
      pyridine (MEP) and the other based on hexylamine (HEA) were investigated with
      regard to their ability to separate proteins when using internally generated,
      retained pH gradients. The effects of added salt and urea on the behavior of the
      retained pH gradient and the protein separation achieved when using MMC column
      packings for chromatofocusing were also investigated. Numerical simulations using
      methods developed in previous work were shown to agree with experimental results
      when using reasonable physical parameters. These numerical simulations were also
      shown to be a useful qualitative method to select the compositions of the
      starting and elution buffers in order to achieve desired shapes for the pH and
      ionic strength gradients. The use of the method to fractionate blood serum was
      explored as a prototype example application. 

PMID- 24296296
TI  - Adamantyl-group containing mixed-mode acrylamide-based continuous beds for
      capillary electrochromatography. Part III. Optimization of the chromatographic
      efficiency.
AB  - In a previous article we described the synthesis of amphiphilic monolithic
      stationary phases by in situ free radical copolymerization of cyclodextrin
      solubilized N-adamantyl acrylamide, piperazinediacrylamide, methacrylamide and
      vinylsulfonic acid in aqueous medium in pre-treated fused silica capillaries of
      100MU.m I.D. In this work, a series of N-adamantyl-group containing acrylamide
      based continuous beds is synthesized under variation of different synthesis
      parameters. The studied synthesis parameters are (i) concentration of the
      lyotropic salt ammonium sulfate, (ii) concentration of the initiator ammonium
      persulfate, and (iii) concentration of the negatively charged monomer
      vinylsulfonic acid in the polymerization mixture. The influence of the synthesis
      parameters on the chromatographic efficiency is studied under isocratic
      conditions for a homologues series of alkylphenones in the reversed-phase mode at
      constant composition of the mobile phase via capillary electrochromatography with
      varied electric field strength. With varied concentration of the lyotropic salt
      ammonium sulfate or varied concentration of the initiator ammonium persulfate in
      the polymerization mixture, a strong impact on the chromatographic efficiency is
      observed, while there is only a minor influence when varying the molar fraction
      of the charged monomer VSA. The absence of a significant influence of extra
      column band broadening effects on the determined efficiency is confirmed. There
      is a good repeatability (with respect to capillary-to-capillary variation and run
      to-run variation) reached for the theoretical plate heights obtained for DMF and
      selected alkylphenones in the reversed-phase mode. 

PMID- 24296297
TI  - Targeted delivery of the RGD-labeled biodegradable polymersomes loaded with the
      hydrophilic drug oxymatrine on cultured hepatic stellate cells and liver fibrosis
      in rats.
AB  - Oxymatrine (OM) is an alkaloid extracted from a Chinese herb that has been found
      to possess an anti-hepatic fibrosis effect, although its anti-fibrotic potential
      is limited due to a lack of targeting specificity, a short half-life and adverse
      effects. Polymersomes (PM) assembled from amphiphilic block copolymers represent
      promising vesicles for applications that include drug delivery and surface
      functionalization. The aim of this study was to develop a novel drug carrier
      based on PM modified with the peptide RGD and evaluate its therapeutic effect on
      liver fibrosis. A series of PM based on poly(ethylene glycol)-b-poly(epsilon
      caprolactone) (PEG-b-PCL) were prepared and characterized. OM was loaded into PM
      by a pH-gradient method then the OM-loaded PM was modified with RGD peptide to
      obtain RGD-PM-OM. The average drug loading of RGD-PM-OM, with a size of 95 nm,
      was 6.8%. The targeting effects of the system were determined in cultured hepatic
      stellate cells (HSCs) and bile duct-ligated rats (BLD). RGD-PM-OM displayed
      better suppression of HSCs proliferation and significantly reduced the expression
      of the genes for alpha-SMA and collagen lalpha1 in cultured HSCs. Furthermore,
      RGD-PM-OM exhibited markedly superior anti-fibrosis activity by reducing the
      levels of PC-III and IV-C in serum and connective tissue deposition in BLD
      compared with PM-OM and OM. These results indicate that targeted RGD-PM-OM
      markedly attenuates the effects of hepatic fibrosis.

PMID- 24296298
TI  - DPP-IV inhibitors: Beyond glycaemic control?
AB  - Dipeptidyl-peptidase-IV (DPP-IV) inhibitors are a new class of oral hypoglycaemic
      agents recently approved for the management of type 2 diabetes mellitus. Early
      data suggested that they had a positive impact on the cardiovascular system:
      treatment appeared to result in improvements in cardiac performance, blood
      pressure and lipid levels. However, recent clinical findings bring this into
      question. Our understanding of the physiological actions of these agents is
      complicated by the fact that DPP-IV has a wide range of substrates in addition to
      glucagon-like peptide 1. Indeed, DPP-IV inhibition alters concentrations of a
      wide variety of cytokines and neuropeptides. A deeper understanding of the
      physiological effects of these drugs as well as their true impact on
      cardiovascular risk is needed before consideration can be given to extending
      their use beyond the treatment of diabetes. 

PMID- 24296299
TI  - Using advanced noninvasive imaging techniques to probe the links between regional
      coronary artery endothelial dysfunction and atherosclerosis.
AB  - Cardiovascular disease remains the number one cause of death in the US annually.
      The development in recent years of imaging strategies that can identify coronary
      endothelial dysfunction noninvasively provides new information about the early
      presence and local spatial heterogeneity of endothelial function in patients
      with, and those at risk for, coronary artery disease. In this article, we will
      briefly review the mechanisms relating endothelial function and atherosclerosis,
      contemporary imaging strategies now able to quantify coronary endothelial
      function noninvasively, and recent insights on human coronary endothelial
      function. 

PMID- 24296300
TI  - Effects of different polymerases of avian influenza viruses on the growth and
      pathogenicity of A/Puerto Rico/8/1934 (H1N1)-derived reassorted viruses.
AB  - We generated reassorted PR8 viruses containing six different combinations of
      avian influenza virus (AIV) polymerase genes from A/chicken/Korea/01310/2001
      (H9N2) (01310) and A/chicken/Korea/KBNP-0028/2000 (H9N2) (0028) to examine the
      effects of the AIV polymerase genes PB1, PB2, and PA on replication efficiency in
      different host cells and pathogenicity in mice. The virus titers of the
      reassorted viruses possessing 01310 [rPR8-PB2(01310)] and 0028 [rPR8-PB2(0028)]
      PB2 genes were significantly higher than those of the others except the rPR8
      virus in embryonated chicken eggs at 37 degrees C, and those of avian polymerase
      reassorted viruses were significantly less than rPR8 in MDCK cells at 32 and 37
      degrees C. rPR8-PB2(01310), rPR8-PB2(0028), and rPR8-PA(0028) caused no body
      weight loss in BALB/c mice but rPR8-PA(01310), rPR8-PB1(01310), and rPR8
      PB1(0028) caused mortality and significantly different body weight loss compared
      to those in the mock treatment. In contrast to rPR8-PB2(0028) and rPR8-PA(0028),
      rPR8-PB2(01310) was not isolated from infected mice, and rPR8-PB1(0028) was less
      pathogenic than rPR8-PB1(01310). We determined the amino acid residues that were
      specific to the less pathogenic polymerases. A comparison with those of pandemic
      2009 H1N1, human fatal H5N1 and H7N9, and pathogenic AIVs to mice without
      adaptation revealed that they possessed the mammalian pathogenic constellation of
      polymerases. Thus, the novel polymerase genes and amino acid residues may be
      useful to understand the host-barrier overcome of AIVs in mice and to develop
      safer and efficacious vaccines. 

PMID- 24296301
TI  - Involvement of reactive oxygen species in brominated diphenyl ether-47-induced
      inflammatory cytokine release from human extravillous trophoblasts in vitro.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds.
      Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners
      found in human breast milk, serum and placenta. Despite the presence of PBDEs in
      human placenta, effects of PBDEs on placental cell function are poorly
      understood. The present study investigated BDE-47-induced reactive oxygen species
      (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine
      release in a first trimester human extravillous trophoblast cell line, HTR
      8/SVneo. Exposure of HTR-8/SVneo cells for 4h to 20MUM BDE-47 increased ROS
      generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise,
      superoxide anion production increased approximately 5 fold at 10 and 15MUM and 9
      fold at 20MUM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction.
      BDE-47 (10, 15 and 20MUM) decreased the mitochondrial membrane potential by 47
      64.5% at 4, 8 and 24h as assessed with the fluorescent probe Rh123. Treatment
      with 15 and 20MUM BDE-47 stimulated cellular release and mRNA expression of IL-6
      and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold
      increased mRNA expression at 12h and a 12-fold increased protein concentration at
      24h for IL-6. Antioxidant treatments (deferoxamine mesylate, (+/-)alpha
      tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3%
      and 37.7%, respectively, implicating a role for ROS in the regulation of
      inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited
      statistically significantly decreased responses compared with non-treated
      controls for IL-6 release and IL-8 mRNA expression, but these responses were not
      consistent across experiments and times. Nonetheless, it is possible that DMSO
      (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47
      on cytokine responses. Because abnormal activation of proinflammatory responses
      can disrupt trophoblast functions necessary for placental development and
      successful pregnancy, further investigation is warranted of the impact of ROS and
      BDE-47 on trophoblast cytokine responses. 

PMID- 24296302
TI  - Arsenic methylation and lung and bladder cancer in a case-control study in
      northern Chile.
AB  - In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA)
      then to dimethylarsenic (DMA), although this process is not complete in most
      people. The trivalent form of MMA is highly toxic in vitro and previous studies
      have identified associations between the proportion of urinary arsenic as MMA
      (%MMA) and several arsenic-related diseases. To date, however, relatively little
      is known about its role in lung cancer, the most common cause of arsenic-related
      death, or about its impacts on people drinking water with lower arsenic
      concentrations (e.g., <200MUg/L). In this study, urinary arsenic metabolites were
      measured in 94 lung and 117 bladder cancer cases and 347 population-based
      controls from areas in northern Chile with a wide range of drinking water arsenic
      concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by
      increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99
      3.67), and 3.26 (1.76-6.04) (p-trend <0.001). Corresponding odds ratios for
      bladder cancer were 1.00, 1.81 (1.06-3.11), and 2.02 (1.15-3.54) (p-trend
      <0.001). In analyses confined to subjects only with arsenic water concentrations
      <200MUg/L (median=60MUg/L), lung and bladder cancer odds ratios for subjects in
      the upper tertile of %MMA compared to subjects in the lower two tertiles were
      2.48 (1.08-5.68) and 2.37 (1.01-5.57), respectively. Overall, these findings
      provide evidence that inter-individual differences in arsenic metabolism may be
      an important risk factor for arsenic-related lung cancer, and may play a role in
      cancer risks among people exposed to relatively low arsenic water concentrations.

PMID- 24296303
TI  - Maternal control of axial-paraxial mesoderm patterning via direct transcriptional
      repression in zebrafish.
AB  - Axial-paraxial mesoderm patterning is a special dorsal-ventral patterning event
      of establishing the vertebrate body plan. Though dorsal-ventral patterning has
      been extensively studied, the initiation of axial-paraxial mesoderm pattering
      remains largely unrevealed. In zebrafish, spt cell-autonomously regulates
      paraxial mesoderm specification and flh represses spt expression to promote axial
      mesoderm fate, but the expression domains of spt and flh initially overlap in the
      entire marginal zone of the embryo. Defining spt and flh territories is therefore
      a premise of axial-paraxial mesoderm patterning. In this study, we investigated
      why and how the initial expression of flh becomes repressed in the ventrolateral
      marginal cells during blastula stage. Loss- and gain-of-function experiments
      showed that a maternal transcription factor Vsx1 is essential for restricting flh
      expression within the dorsal margin and preserving spt expression and paraxial
      mesoderm specification in the ventrolateral margin of embryo. Chromatin
      immunoprecipitation and electrophoretic mobility shift assays in combination with
      core consensus sequence mutation analysis further revealed that Vsx1 can directly
      repress flh by binding to the proximal promoter at a specific site. Inhibiting
      maternal vsx1 translation resulted in confusion of axial and paraxial mesoderm
      markers expression and axial-paraxial mesoderm patterning. These results
      demonstrated that direct transcriptional repression of the decisive axial
      mesoderm gene by maternal ventralizing factor is a crucial regulatory mechanism
      of initiating axial-paraxial mesoderm patterning in vertebrates. 

PMID- 24296304
TI  - Effects of dietary katuk (Sauropus androgynus L. Merr.) on growth, non-specific
      immune and diseases resistance against Vibrio alginolyticus infection in grouper
      Epinephelus coioides.
AB  - This study was conducted to investigate the effect of katuk (Sauropus androgynus
      L. Merr) on growth, non-specific immune and diseases resistance against Vibrio
      alginolyticus in grouper (Epinephelus coioides). Grouper juveniles (mean weight
      10.97 +/- 1.99 g, and length 9.67 +/- 0.33 cm) were separated into four groups
      and cultivated in 100-L tank. Each group was fed with diets containing 0, 1.0,
      2.5 and 5.0 g/kg herbs diet twice daily. Fish were sampled for non-specific
      immune parameters at 0, 1, 2, 4, 7, 14 and 30 days. Results showed that fish
      received S. androgynus at 1.0 and 2.5 g/kg diets affected the growth and non
      specific immune responses. Weight gain, specific growth rate, respiratory burst
      activity, phagocytosis and reactive oxygen species significantly increased in
      fish administered with 1.0 and 2.5 g/kg S. androgynus diets. The mortality rate
      after V. alginolyticus challenge decreased in fish fed with 1.0 g/kg S.
      androgynus extract. Thus, this study indicated that administration of grouper
      with S. androgynus supplemented diets can affect the growth performances,
      diseases resistance and enhances non-specific immune responses. 

PMID- 24296305
TI  - Adiponectin links adipose tissue function and monocyte inflammatory responses
      during bovine metabolic stress.
AB  - The periparturient period of dairy cows is characterized by intense lipid
      mobilization from adipose tissue leading to increased plasma concentrations of
      nonesterified fatty acids (NEFA). High NEFA are a predisposing factor for
      inflammatory based diseases. A major component of these diseases is uncontrolled
      macrophage/monocyte inflammatory responses. Changes in the endocrine activity of
      adipose tissue during the periparturient period could impact macrophage function
      by modifying the secretion of adipokines including adiponectin. Currently, the
      effects of adiponectin on monocyte activation in dairy cattle are unknown. In
      humans and rodents, this adipokine regulates monocyte phenotype and alterations
      in its plasma levels are linked with the development of inflammatory diseases.
      The objectives of this study were to establish associations between plasma
      adiponectin expression dynamics and different markers of lipid mobilization
      during the periparturient period of dairy cows and to characterize the effects of
      adiponectin on the inflammatory response of bovine monocytes. Plasma adiponectin,
      NEFA, BHB, albumin, and subcutaneous and retroperitoneal fat depots depth were
      measured during the periparturient period of dairy cows. In vitro, bovine
      monocytes were cultured with adiponectin to assess changes in pro-inflammatory
      responses following LPS stimulation. Results from this study demonstrate that
      alterations in plasma adiponectin levels in periparturient cattle are inversely
      correlated with the concentrations of plasma NEFA, an important marker of lipid
      mobilization. Furthermore, adiponectin exposure significantly decreased monocyte
      expression of TNFalpha after LPS stimulation thus markedly reducing their
      inflammatory response. Reduced plasma adiponectin during the periparturient
      period could predispose dairy cows to the development of uncontrolled monocyte
      inflammatory responses. 

PMID- 24296306
TI  - Acute mitral regurgitation: unforeseen new complication of the Impella LP 5.0
      ventricular assist device and review of literature.
AB  - Impella LP 5.0 (Abiomed) is a relatively new technology that has been used over
      the last few years as a ventricular assist device to provide full circulatory
      support for patients presenting with cardiogenic shock. There is limited evidence
      available in literature with regard to insertion approaches, safety,
      complications and long-term clinical outcomes. Complications that have been
      reported are device malfunction, pump displacement, intravascular haemolysis,
      intra-ventricular thrombosis, functional mitral stenosis due to displacement and
      local vascular complications at vascular access site. We report here the first
      case with acute mitral regurgitation due to chordal rupture and flail mitral
      valve leaflet as a result of Impella device displacement, a new complication.
      Review of literature is also reported. 

PMID- 24296307
TI  - Cataract extraction surgery in patients with uveitis in Taiwan: risk factors and
      outcomes.
AB  - BACKGROUND/PURPOSE: To analyze the preoperative conditions and postoperative
      outcomes of phacoemulsification and intraocular lens implantation in Taiwanese
      patients with uveitis. METHODS: This retrospective, consecutive case series study
      included 121 eyes of 84 patients with uveitis who underwent phacoemulsification
      and intraocular lens implantation from July 1996 to May 2006. The demographic
      data, postoperative outcomes, complications, and risk factors with regard to
      visual prognosis were analyzed. Visual acuity was converted from the Snellen
      equivalent to logMAR values. RESULTS: This study included 51 men and 70 women
      with a mean +/- SD age of 44.6 +/- 18.4 years. The three most common diseases
      were idiopathic uveitis, Behcet's disease, and Vogt-Koyanagi-Harada disease. The
      best-corrected visual acuity improved from 1.52 +/- 0.83 logMAR units
      preoperatively to 0.37 +/- 0.59 logMAR units postoperative (p < 0.001). The most
      frequent postoperative complications were posterior capsular opacity (24 eyes)
      and cystoid macular edema (10 eyes). Anterior uveitis related to HLA-B27 had the
      best visual prognosis, whereas Behcet's disease had the poorest visual outcome (p
      = 0.029). Logistic regression analysis indicated that disease etiology (p =
      0.011) and preoperative visual acuity (p = 0.020) were related to the
      postoperative visual prognosis. CONCLUSION: Cataract extraction can improve
      visual function for most patients with uveitis. Postoperative complications were
      not uncommon and Behcet's disease had the poorest postoperative visual prognosis.

PMID- 24296309
TI  - Response to comments on: Laparoscopic distal ureterectomy for urothelial
      carcinoma is technically feasible...but is it oncologically safe?

PMID- 24296308
TI  - Utilization of emergency medical service increases chance of thrombolytic therapy
      in patients with acute ischemic stroke.
AB  - BACKGROUND/PURPOSE: To determine whether utilization of emergency medical service
      (EMS) can increase use and expedite delivery of the thrombolytic therapy in acute
      ischemic stroke patients. METHODS: We analyzed consecutive patients presenting to
      the emergency department (ED) with an ischemic stroke within 72 hours of symptom
      onset from a prospective stroke registry. Variables associated with early ED
      arrival (within 3 hours of stroke onset) and administration of intravenous
      thrombolytic therapy were analyzed. RESULTS: From January 1, 2010 to July 31,
      2011, there were 1081 patients (62.3% men, age 69.6 +/- 13 years) included in
      this study. Among them, 289 (26.7%) arrived in the ED within 3 hours, and 88
      (8.1%) received thrombolytic therapy. Patients who arrived at the ED by EMS (n =
      279, 25.8%) were independently associated with earlier ED arrival (adjusted odds
      ratio = 3.68, 95% confidence interval = 2.54-5.33), and higher chance of
      receiving thrombolytic therapy (adjusted odds ratio = 3.89, 95% confidence
      interval = 1.86-8.17). Furthermore, utilization of EMS significantly decreased
      onset-to-needle time by 26 minutes in patients receiving thrombolytic therapy.
      CONCLUSION: Utilization of EMS can not only help acute ischemic stroke patients
      in early presentation to ED, but also effectively facilitate thrombolytic therapy
      and shorten the onset-to-needle time.

PMID- 24296310
TI  - Laparoscopic distal ureterectomy for urothelial carcinoma is technically
      feasible... but is it oncologically safe?

PMID- 24296311
TI  - Editorial for "Recent advances in DNA-based biosensor".

PMID- 24296312
TI  - Linking gamma-aminobutyric acid A receptor to epidermal growth factor receptor
      pathways activation in human prostate cancer.
AB  - Neuroendocrine (NE) differentiation has been attributed to the progression of
      castration-resistant prostate cancer (CRPC). Growth factor pathways including the
      epidermal growth factor receptor (EGFR) signaling have been implicated in the
      development of NE features and progression to a castration-resistant phenotype.
      However, upstream molecules that regulate the growth factor pathway remain
      largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and
      androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate
      cancer (PCa) patients, we demonstrated that gamma-aminobutyric acid A receptor
      (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation,
      enhance EGF family members expression, and activate EGFR and a downstream
      signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R
      antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839
      or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans
      phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell
      lines. Spatial distributions of GABAAR alpha1 and phosphorylated Src (Tyr416)
      were studied in human prostate tissues by immunohistochemistry. In contrast to
      extremely low or absence of GABA(A)R alpha1-positive immunoreactivity in normal
      prostate epithelium, elevated GABA(A)R alpha1 immunoreactivity was detected in
      prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src
      (Tyr416) was specifically localized and limited to the nucleoli of all invasive
      prostate carcinoma cells, but negative in normal tissues. Strong GABAAR alpha1
      immunoreactivity was spatially adjacent to the neoplastic glands where strong
      phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in
      adjacent to normal glands. These results suggest that the GABA signaling is
      linked to the EGFR pathway and may work through autocrine or paracine mechanism
      to promote CRPC progression.

PMID- 24296313
TI  - Efficient prediction of protein conformational pathways based on the hybrid
      elastic network model.
AB  - Various computational models have gained immense attention by analyzing the
      dynamic characteristics of proteins. Several models have achieved recognition by
      fulfilling either theoretical or experimental predictions. Nonetheless, each
      method possesses limitations, mostly in computational outlay and physical
      reality. These limitations remind us that a new model or paradigm should advance
      theoretical principles to elucidate more precisely the biological functions of a
      protein and should increase computational efficiency. With these critical
      caveats, we have developed a new computational tool that satisfies both physical
      reality and computational efficiency. In the proposed hybrid elastic network
      model (HENM), a protein structure is represented as a mixture of rigid clusters
      and point masses that are connected with linear springs. Harmonic analyses based
      on the HENM have been performed to generate normal modes and conformational
      pathways. The results of the hybrid normal mode analyses give new physical
      insight to the 70S ribosome. The feasibility of the conformational pathways of
      hybrid elastic network interpolation (HENI) was quantitatively evaluated by
      comparing three different overlap values proposed in this paper. A remarkable
      observation is that the obtained mode shapes and conformational pathways are
      consistent with each other. Our timing results show that HENM has some advantage
      in computational efficiency over a coarse-grained model, especially for large
      proteins, even though it takes longer to construct the HENM. Consequently, the
      proposed HENM will be one of the best alternatives to the conventional coarse
      grained ENMs and all-atom based methods (such as molecular dynamics) without loss
      of physical reality. 

PMID- 24296314
TI  - Perceptual learning: top to bottom.
AB  - Perceptual learning has traditionally been portrayed as a bottom-up phenomenon
      that improves encoding or decoding of the trained stimulus. Cognitive skills such
      as attention and memory are thought to drive, guide and modulate learning but
      are, with notable exceptions, not generally considered to undergo changes
      themselves as a result of training with simple perceptual tasks. Moreover, shifts
      in threshold are interpreted as shifts in perceptual sensitivity, with no
      consideration for non-sensory factors (such as response bias) that may contribute
      to these changes. Accumulating evidence from our own research and others shows
      that perceptual learning is a conglomeration of effects, with training-induced
      changes ranging from the lowest (noise reduction in the phase locking of auditory
      signals) to the highest (working memory capacity) level of processing, and
      includes contributions from non-sensory factors that affect decision making even
      on a "simple" auditory task such as frequency discrimination. We discuss our
      emerging view of learning as a process that increases the signal-to-noise ratio
      associated with perceptual tasks by tackling noise sources and inefficiencies
      that cause performance bottlenecks, and present some implications for training
      populations other than young, smart, attentive and highly-motivated college
      students. 

PMID- 24296315
TI  - Hypotensive and vascular relaxant effects of phospholipase A2 toxins from Papuan
      taipan (Oxyuranus scutellatus) venom.
AB  - Phospholipase A2 (PLA2) toxins are common and abundant components of Australasian
      elapid venoms. These toxins are associated with a range of activities including
      neurotoxicity, myotoxicity and coagulation disturbances. We have recently
      reported that sudden cardiovascular collapse induced by Papuan taipan (Oxyuranus
      scutellatus) venom involves a combination of the release of dilator autacoids and
      a direct effect on the smooth muscle. In this study, we aimed to isolate PLA2
      components from Papuan taipan venom and investigate their contribution to the
      hypotensive action of this venom. O. scutellatus venom was fractionated using
      size-exclusion high performance liquid chromatography (HPLC), and fractions
      screened for activity in anaesthetized rats. Fraction three from O. scutellatus
      venom (i.e. OSC3, 14.2+/-1.0% of whole venom) produced a 64% decrease in mean
      arterial pressure. Reverse-phase HPLC indicated that OSC3 consisted of two major
      components (i.e. OSC3a and OSC3b). OSC3a and OSC3b produced a significant
      hypotensive response in anaesthetized rats which were attenuated by prior
      administration of indomethacin or the combination of mepyramine and heparin. N
      terminal analysis indicated that OSC3a and b displayed sequence homology to PLA2
      toxins isolated from coastal taipan (O. scutellatus scutellatus) venom. These
      findings indicate that PLA2 components may play an important role in the
      development of hypotension and vascular relaxation which may contribute to the
      effects observed after envenoming by these Australasian elapids. 

PMID- 24296316
TI  - Contribution of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway to ischemia/reperfusion
      induced oxidative/nitrosative stress and inflammation leading to distant and
      target organ injury in rats.
AB  - The small G protein RhoA and its downstream effector Rho-kinase play an important
      role in various physiopathological processes including ischemia/reperfusion (I/R)
      injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase
      are important mediators of inflammation and organ injury following an initial
      localized I/R event. The aim of this study was to determine whether RhoA/Rho
      kinase signaling pathway increases the expression and activity of MEK1, ERK1/2,
      iNOS, gp91(phox), and p47(phox), and peroxynitrite formation which result in
      oxidative/nitrosative stress and inflammation leading to hindlimb I/R-induced
      injury in kidney as a distant organ and gastrocnemius muscle as a target organ.
      I/R-induced distant and target organ injury was performed by using the rat
      hindlimb tourniquet model. I/R caused an increase in the expression and/or
      activity of RhoA, MEK1, ERK1/2, iNOS, gp91(phox), p47(phox), and 3-nitrotyrosine
      and nitrotyrosine levels in the tissues. Although Rho-kinase activity was
      increased by I/R in the kidney, its activity was decreased in the muscle. Serum
      and tissue MDA levels and MPO activity were increased following I/R. I/R also
      caused an increase in SOD and catalase activities associated with decreased GSH
      levels in the tissues. Y-27632, a selective Rho-kinase inhibitor, (100ug/kg,
      i.p.; 1h before reperfusion) prevented the I/R-induced changes except Rho-kinase
      activity in the muscle. These results suggest that activation of RhoA/Rho
      kinase/MEK1/ERK1/2/iNOS pathway associated with oxidative/nitrosative stress and
      inflammation contributes to hindlimb I/R-induced distant organ injury in rats. It
      also seems that hindlimb I/R induces target organ injury via upregulation of
      RhoA/MEK1/ERK1/2/iNOS pathway associated with decreased Rho-kinase activity. 

PMID- 24296317
TI  - Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced
      tumour suppressor genes and inhibits cell growth in breast cancer cells.
AB  - Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine, ClF) is a second
      generation 2'-deoxyadenosine analogue that is structurally related to cladribine
      (2-chloro-2'-deoxyadenosine, 2CdA) and fludarabine (9-beta-d-arabinosyl-2
      fluoroadenine, F-ara-A). It demonstrates potent antitumour activity at much lower
      doses than parent compounds with high therapeutic efficacy in paediatric blood
      cancers. Our previous studies in breast cancer cells indicate that 2CdA and F-ara
      A are involved in epigenetic regulation of gene transcription. We therefore
      investigated whether ClF influences methylation and expression of selected tumour
      suppressor genes, such as adenomatous polyposis coli (APC), phosphatase and
      tensin homologue (PTEN), and retinoic acid receptor beta 2 (RARbeta2), as well as
      expression of p53, p21 and DNA methyltransferase 1 (DNMT1) in MCF-7 and MDA-MB
      231 breast cancer cell lines with different invasive potential. Promoter
      methylation and gene expression were estimated using methylation-sensitive
      restriction analysis (MSRA) and real-time PCR, respectively. ClF demonstrated
      potent growth inhibitory activity in MCF-7 and MDA-MB-231 cells after 96h
      treatment with IC50 determined as equal to 640nM and 50nM, respectively. In both
      breast cancer cell lines, ClF led to hypomethylation and up-regulation of APC,
      PTEN and RARbeta2 as well as increase in p21 expression. Only in non-invasive MCF
      7 cells, these changes were associated with down-regulation of DNMT1. Our results
      provide first evidence of ClF implications in epigenetic regulation of
      transcriptional activity of selected tumour suppressor genes in breast cancer. It
      seems to be a new important element of ClF anticancer activity and may indicate
      its potential efficacy in epigenetic therapy of solid tumours, especially at
      early stages of carcinogenesis. 

PMID- 24296318
TI  - Underlying mechanisms involved in progesterone-induced relaxation to the pig
      bladder neck.
AB  - Progesterone increases bladder capacity and improves the bladder compliance by
      its relaxant action on the detrusor. A poor information, however, exists
      concerning to the role of this steroid hormone on the bladder outflow region
      contractility. This study investigates the progesterone-induced action on the
      smooth muscle tension of the pig bladder neck. To this aim, urothelium-denuded
      bladder neck strips were mounted in myographs for isometric force recordings and
      for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)]i)
      and tension. On phenylephrine (PhE)-precontracted strips, progesterone produced
      concentration-dependent relaxations only at high pharmacological concentrations.
      The blockade of progesterone receptors, nitric oxide (NO) synthase, guanylyl
      cyclase, large conductance Ca(2+)-activated K(+) (BKCa) or ATP-dependent K(+)
      (KATP) channels reduced the progesterone relaxations. The presence of the
      urothelium and the inhibition of cyclooxygenase (COX), intermediate- and small
      conductance Ca(2+)-activated K(+) channels failed to modify these responses. In
      Ca(2+)-free potassium rich physiological saline solution, progesterone inhibited
      the contraction to CaCl2 and to the L-type voltage-operated Ca(2+) (VOC) channel
      activator BAY-K 8644. Relaxation induced by progesterone was accompanied by
      simultaneous decreases in smooth muscle [Ca(2+)]i. These results suggest that
      progesterone promotes relaxation of pig bladder neck through smooth muscle
      progesterone receptors via cGMP/NO pathway and involving the activation of BKCa
      and KATP channels and inhibition of the extracellular Ca(2+) entry through L-type
      VOC channels. 

PMID- 24296319
TI  - Effects of HMG-CoA reductase inhibitors on learning and memory in the guinea pig.
AB  - Statins reduce the risk of death from cardiovascular disease in millions of
      people worldwide. Recent pharmacovigilance data has suggested that people taking
      statins have an increased risk of psychiatric adverse events such as amnesia and
      anxiety. This study aimed to investigate the possibility of statin-induced
      amnesia through animal models of memory and learning. We conducted extracellular
      field recordings of synaptic transmission in area CA1 of hippocampal slices to
      examine the effects of acute cholesterol lowering with lipid lowering drugs. We
      also assessed the effect of six weeks of simvastatin (2mg/kg/d) and atorvastatin
      (1mg/kg/d) treatment using the Morris water maze. Long Term Potentiation (LTP)
      was significantly diminished in the presence of 3uM atorvastatin or simvastatin
      and by the cholesterol sequestering agent methyl-beta-cyclodextrin (MBCD). The
      effects were reversed in the MBCD but not the statin treated slices by the
      addition of cholesterol. In the water maze, statin treatment did not cause any
      deficits in the first five days of reference memory testing, but statin treated
      guinea pigs preformed significantly worse than control animals in a working
      memory test. The deficits observed in our experiments in water maze performance
      and hippocampal LTP are suggestive of statin induced changes in hippocampal
      plasticity. The effects on LTP are independent of cholesterol regulation, and
      occur at concentrations that may be relevant to clinical use. Our results may
      help to explain some of the behavioural changes reported in some people after
      beginning statin treatment. 

PMID- 24296320
TI  - Inhibitory effect of spinal mGlu(5) receptor antisense oligonucleotide on the up
      regulated expression of spinal G protein associated with chronic morphine
      treatment.
AB  - Knockdown of spinal metabotropic glutamate 5 (mGlu5) receptor was shown to
      inhibit the development of intrathecal morphine antinociceptive tolerance. The
      present work was designed to evaluate the expression of spinal G-protein during
      morphine tolerance and knockdown of spinal mGlu5 receptor with antisense
      oligonucleotide (ODN). Rats were treated with saline, morphine, mGlu5 receptor
      antisense or mismatch ODN intrathecally. Behavioral tests were employed to test
      the thermal and mechanical pain thresholds. Five days later, rats were scarified
      and spinal expression of spinal Galphai, Galphao, Galphaq and Gbeta were
      detected. Consistent with the previous results, knockdown of spinal mGlu5
      receptor could inhibit spinal morphine antinociceptive tolerance in behavioral
      tests (P<0.05). The mGlu5 receptor antisense ODN produced a significant reduction
      in mGlu5 receptor protein of about 56.6% compared with the control group
      (P<0.05). Expression of spinal Galphai, Galphao, Galphaq and Gbeta were up
      regulated while morphine tolerance developed (P<0.05). Antisense ODN of spinal
      mGlu5 receptor, but not mismatched ODN, reduced the spinal dorsal horn levels of
      Galphai, Galphao, Galphas, Galphaq and Gbeta (P<0.05). We conclude that
      expression of spinal G (alphai, alphao, alphas, alphaq and beta) protein may be
      up-regulated after chronic morphine treatment which could be attenuated by
      knockdown of spinal mGlu5 receptor with antisense ODN. 

PMID- 24296321
TI  - Central site monitoring: results from a test of accuracy in identifying trials
      and sites failing Food and Drug Administration inspection.
AB  - BACKGROUND: Site monitoring and source document verification account for 15%-30%
      of clinical trial costs. An alternative is to streamline site monitoring to focus
      on correcting trial-specific risks identified by central data monitoring. This
      risk-based approach could preserve or even improve the quality of clinical trial
      data and human subject protection compared to site monitoring focused primarily
      on source document verification. PURPOSE: To determine whether a central review
      by statisticians using data submitted to the Food and Drug Administration (FDA)
      by clinical trial sponsors can identify problem sites and trials that failed FDA
      site inspections. METHODS: An independent Analysis Center (AC) analyzed data from
      four anonymous new drug applications (NDAs) where FDA had performed site
      inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team
      members in the OSI chose the four NDAs from among all NDAs with data in Study
      Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed
      unreliable in support of the application after FDA site inspections identified
      serious data integrity problems. The other two NDAs had clinical data that OSI
      deemed reliable after site inspections. At the outset, the AC knew only that the
      experimental design specified two NDAs with significant problems. FDA gave the AC
      no information about which NDAs had problems, how many sites were inspected, or
      how many were found to have problems until after the AC analysis was complete.
      The AC evaluated randomization balance, enrollment patterns, study visit
      scheduling, variability of reported data, and last digit reference. The AC
      classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No
      Concern'. RESULTS: The AC correctly identified the two NDAs with data deemed
      unreliable by OSI. In addition, central data analysis correctly identified 5 of 6
      (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%)
      for which any regulatory deviations were identified during inspection. Of the six
      sites for which OSI reviewed inspections and found no deviations, the central
      process flagged four at the lowest level of concern, one at a moderate level, and
      one was not flagged. LIMITATIONS: Central data monitoring during the conduct of a
      trial while data checking was in progress was not evaluated. CONCLUSION:
      Systematic central monitoring of clinical trial data can identify problems at the
      same trials and sites identified during FDA site inspections. Central data
      monitoring in conjunction with an overall monitoring process that adapts to
      identify risks as a trial progresses has the potential to reduce the frequency of
      site visits while increasing data integrity and decreasing trial costs compared
      to processes that are dependent primarily on source documentation.

PMID- 24296322
TI  - Understanding and retention of trial-related information among participants in a
      clinical trial after completing the informed consent process.
AB  - BACKGROUND METHODS: for assessing the level of understanding of trial-related
      information during the informed consent (IC) process in developing countries are
      lacking. PURPOSE: To assess the understanding and retention of trial-related
      information presented in the IC process by administering an informed consent
      assessment instrument (ICAI) to participants in a clinical trial for a new
      tuberculosis (TB) regimen being conducted in Rio de Janeiro (Brazil). Methods The
      format of the ICAI was based on the language and structure of the United States
      National Cancer Institute's IC comprehension checklist. The ICAI was designed to
      assess points of the RioMAR study IC process that addressed the principles of
      research ethics requested by Brazilian Regulatory Authority: autonomy,
      beneficence, non-maleficence, and justice. Briefly, (1) Is the respondent
      participating in a clinical trial? (2) Are two different treatments being
      evaluated? (3) Is the treatment arm chosen by chance? (4) Is an HIV test
      required? (5) Are liver function tests required? (6) Can participants leave the
      study at any time? (7) Are the risks and benefits of taking part in the study
      clear? (8) May pregnant women participate in the study? (9) Can one of the study
      drugs reduce the effectiveness of contraceptives? (10) Are patients paid to
      participate in the study? The ICAI was applied at two time points: immediately
      after enrollment in the clinical trial and 2 months later. RESULTS: A total of 61
      patients who enrolled in the RioMAR study participated in this study. The
      percentage of correct answers to all questions was 82% at the time of the first
      ICAI; 31 participants (51%) did not recall that an HIV test was required
      (question 4) and 43 (70%) did not know that they could leave the study (question
      6). Other individual questions were answered correctly by at least 76% of
      participants. There was no association between incorrect answers and age, gender,
      monthly family income, neighborhood, or level of education (p > 0.07). When the
      responses to the first and the second ICAI questions were compared, 15% or more
      of participants had conflicting answers to 5 of the 10 questions. LIMITATIONS:
      The ICAI uses dichotomous responses, leading to a 50% chance of guessing the
      correct answers. Two questions were asked only of women. Finally, only 6 of the
      10 questions on the current version of the ICAI apply to most trials; others are
      trial-specific. CONCLUSIONS: The ICAI may be adapted to an individual trial and
      may prove to be a useful tool following a consent discussion to identify issues
      not fully understood by the research participants, thus prompting study staff to
      re-explain topics, possibly in a more elementary manner.

PMID- 24296323
TI  - Etamicastat, a novel dopamine beta-hydroxylase inhibitor: tolerability,
      pharmacokinetics, and pharmacodynamics in patients with hypertension.
AB  - BACKGROUND: Etamicastat is a dopamine beta-hydroxylase (DbetaH) inhibitor
      currently in clinical development for the treatment of hypertension and heart
      failure. OBJECTIVE: This study assessed the tolerability, pharmacokinetics, and
      pharmacodynamics of etamicastat in patients with arterial hypertension. METHODS:
      This randomized, double-blind, placebo-controlled study was conducted in male
      patients aged between 18 and 65 years with mild to moderate hypertension.
      Participants received once-daily doses of etamicastat 50, 100, or 200 mg or
      placebo for 10 days. Antihypertensive effect was assessed by 24-hour ambulatory
      blood pressure monitoring (ABPM). RESULTS: The study enrolled 23 male volunteers,
      with ages between 49 and 64 years. There were no serious adverse events reported.
      All adverse events were mild to moderate in intensity and resolved without
      sequelae. Etamicastat Tmax was 1 hour postdose, and mean t1/2 was 19 to 28 hours
      following repeated administration. Etamicastat underwent N-acetylation by N
      acetyltransferase 2 (NAT2), forming the metabolite BIA 5-961. Following repeated
      administration, mean etamicastat AUC was 2- to 3-fold greater in poor acetylators
      than in rapid acetylators. Approximately 50% of the etamicastat dose was
      recovered in urine-30% as unchanged etamicastat and 20% as BIA 5-961. Dose
      dependent decreases in systolic and diastolic blood pressure were observed after
      10 days of treatment. The mean (95% CI) decreases versus placebo in nighttime SBP
      were statistically significant with all 3 etamicastat doses (50 mg, -11.66 mm Hg
      [-21.57 to -1.76; P < 0.05]; 100 mg, -14.92 mm Hg [-24.98 to -4.87; P < 0.01];
      and 200 mg, -13.62 mm Hg [-22.29 to -3.95; P < 0.01]). CONCLUSIONS: Etamicastat
      was well tolerated and showed a pharmacokinetic profile consistent with a once
      daily regimen. NAT2 phenotype markedly affected the pharmacokinetics. The
      antihypertensive effect of etamicastat, assessed by 24-hour ABPM, was dose
      dependent up to 100 mg. The assessment of etamicastat as a novel antihypertensive
      therapy requires further study in broader populations. EudraCT trial registration
      2008-002789-09.

PMID- 24296324
TI  - Comparison of the effects of amlodipine and losartan on blood pressure and
      diurnal variation in hypertensive stroke patients: a prospective, randomized,
      double-blind, comparative parallel study.
AB  - BACKGROUND: Lowering blood pressure (BP) and reducing diurnal variation are
      important for the prevention of stroke in patients with hypertension. OBJECTIVE:
      This study was conducted to compare the BP-lowering and diurnal BP variation
      effects of amlodipine and losartan on acute stroke patients. METHODS: Seventy
      seven hypertensive patients with acute stroke were enrolled in this randomized,
      double-blind, single-center clinical trial. They were randomly assigned to
      receive either amlodipine or losartan daily. To evaluate whether amlodipine was
      noninferior to losartan, ambulatory BP monitoring was performed before the drugs
      were first administered and at the end of week 8. BP variables analyzed included
      the mean awake, sleep, morning, evening, and prewake BP values; the nocturnal
      dipping status; and the morning surge. RESULTS: Thirty-nine patients in the
      amlodipine group and 38 patients in the losartan group completed the follow-up.
      In the baseline characteristics, mean age was 63.6 years, and 68.8% were male. In
      the intention-to-treat analysis, the mean (SD) systolic BP decreased 14.82
      (11.71) mm Hg in the amlodipine group and 13.11 (12.69) mm Hg in the losartan
      group, and amlodipine proved noninferior to losartan (mean difference, 1.71 mm Hg
      [95% CI, -3.83 to 7.26]). However, in the per-protocol analysis, noninferiority
      was not proven (BP reduction, 16.06 [11.33] vs 17.17 [11.85] mm Hg; mean
      difference, -1.11 mm Hg [95% CI, -6.88 to 4.65]). Amlodipine had a greater
      tendency than losartan to produce a blunt morning surge. CONCLUSIONS: The
      noninferiority of amlodipine was not confirmed by the per-protocol analysis.
      However, amlodipine showed a favorable effect on the morning surge.
      ClinicalTrials.gov identifier: NCT01830517.

PMID- 24296325
TI  - Feasibility, safety and effectiveness of combining home based malaria management
      and seasonal malaria chemoprevention in children less than 10 years in Senegal: a
      cluster-randomised trial.
AB  - BACKGROUND: Home-based management of malaria (HMM) may improve access to
      diagnostic testing and treatment with artemisinin combination therapy (ACT). In
      the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for
      the prevention of malaria in children. It is likely that combinations of
      antimalarial interventions can reduce the malaria burden. This study assessed the
      feasibility, effectiveness and safety of combining SMC and HMM delivered by
      community health workers (CHWs). METHODS: A cluster-randomised trial was carried
      out during two transmission seasons in eight villages located in the south
      eastern part of Senegal. Intervention communities received HMM+SMC while control
      communities received HMM. Primary end point was the incidence of malaria attacks
      during the follow up period. Secondary end points included: malaria diagnostic
      accuracy; access to ACT treatment; SMC coverage; safety and drug tolerability.
      RESULTS: The adjusted rate ratio for incidence of malaria attacks in intervention
      and control communities was 0.15, indicating a protective effect of HMM+SMC of
      85% (95% CI: 39.9-96.3%, p=0.01). Access to ACT treatment was 96.4% while SMC
      coverage represented 97.3% (95% CI: 91.3-100%) in 2010, and 88.8% (95% CI: 84.2
      93.6%) in 2011. No serious adverse events were recorded. CONCLUSION: It seems
      feasible and safe to combine SMC with HMM intervention, while achieving high
      coverage and effectiveness of both SMC and HMM. TRIAL REGISTRATION:
      (www.pactr.org) PACTR201305000551876.

PMID- 24296326
TI  - New horizons and hurdles for UK radiotherapy: can prostate stereotactic body
      radiotherapy show the way?

PMID- 24296327
TI  - Response to D. Woolf and M. Keshtgar's reply to: breast radiotherapy and heart
      disease - where are we now?

PMID- 24296328
TI  - Estrogenic action on innate defense mechanisms in the urinary tract.
AB  - Clinical data suggest an impact of estrogen on the pathogenesis of urinary tract
      infections (UTI). In particular, women after menopause often suffer from
      recurrent UTI, characterized by at least three acute UTI episodes within a year.
      Aside from bacterial factors promoting persistence within the urinary bladder,
      the low estrogen levels induce structural and chemical changes in the urogenital
      tract which facilitate UTI. Increased residual urine volume and changes in the
      vaginal microflora are well documented risk factors. Local supplementation with
      estrogen can at least partly reverse these changes. Treatment allows the re
      establishment of a lactobacilli-dominated vaginal microflora and improves
      epithelial differentiation and integrity in the urogenital tract. This estrogenic
      effect on the epithelium is marked by an increased production of antimicrobial
      peptides and a tighter intercellular connection, preventing bacteria from
      reaching cells where they can hide and later emerge and cause a new infection.
      Estrogen in the dosages and applications used to date is considered safe for the
      endometrium in the majority of women. Based on the actions and safety of
      estrogen, local supplementation thus offers a treatment option for postmenopausal
      women suffering from recurrent UTI. 

PMID- 24296329
TI  - Retroperitoneal laparoscopic partial nephrectomy for moderately complex renal
      hilar tumors.
AB  - OBJECTIVES: To report our initial experience in retroperitoneal laparoscopic
      partial nephrectomy (LPN) for moderately complex renal hilar tumors and summarize
      the feasibility of the retroperitoneal laparoscopic approach. MATERIALS AND
      METHODS: 14 patients with renal hilar tumors underwent retroperitoneal LPN
      between June 2010 and January 2012 at our institution. All of the masses were
      confirmed in the hilar location by computed tomography preoperatively and then
      evaluated with the R.E.N.A.L. nephrometry scoring system; all were defined as
      moderately complex lesions. A three-port retroperitoneal approach with a dorsal
      incision was used in all cases. Patient baseline demographics, perioperative
      outcomes and pathological characteristics were recorded based on a retrospective
      data collection and telephone interview. RESULTS: All operations were performed
      successfully without conversion to radical nephrectomy or open surgery. Only two
      complications of perirenal fluid collection occurred, but the patients recovered
      with active surveillance. Mean operative time was 134.3 min, mean estimated blood
      loss 133.2 ml, mean warm ischemia time 30.6 min and mean retroperitoneal drainage
      2.2 days. Mean postoperative hospital stay was 4.7 days. No recurrence or
      metastasis occurred in these patients at a mean follow-up of 18.6 months.
      CONCLUSIONS: Our initial experience suggests that retroperitoneal LPN is a
      feasible, safe and effective procedure for moderately complex renal hilar tumors.
      Although it remains technically challenging, this approach can be recommended in
      some complex cases when in experienced hands.

PMID- 24296330
TI  - Searchlight-based multi-voxel pattern analysis of fMRI by cross-validated MANOVA.
AB  - Multi-voxel pattern analysis (MVPA) is a fruitful and increasingly popular
      complement to traditional univariate methods of analyzing neuroimaging data. We
      propose to replace the standard 'decoding' approach to searchlight-based MVPA,
      measuring the performance of a classifier by its accuracy, with a method based on
      the multivariate form of the general linear model. Following the well-established
      methodology of multivariate analysis of variance (MANOVA), we define a measure
      that directly characterizes the structure of multi-voxel data, the pattern
      distinctness D. Our measure is related to standard multivariate statistics, but
      we apply cross-validation to obtain an unbiased estimate of its population value,
      independent of the amount of data or its partitioning into 'training' and 'test'
      sets. The estimate D^ can therefore serve not only as a test statistic, but also
      as an interpretable measure of multivariate effect size. The pattern distinctness
      generalizes the Mahalanobis distance to an arbitrary number of classes, but also
      the case where there are no classes of trials because the design is described by
      parametric regressors. It is defined for arbitrary estimable contrasts, including
      main effects (pattern differences) and interactions (pattern changes). In this
      way, our approach makes the full analytical power of complex factorial designs
      known from univariate fMRI analyses available to MVPA studies. Moreover, we show
      how the results of a factorial analysis can be used to obtain a measure of
      pattern stability, the equivalent of 'cross-decoding'. 

PMID- 24296331
TI  - Differential effects of the ApoE4 genotype on brain structure and function.
AB  - The apolipoprotein E epsilon4 allele is a well established genetic risk factor
      for sporadic Alzheimer's disease. It is associated with structural and functional
      brain changes in healthy young, middle-aged and elderly subjects. In the current
      study, we assessed the impact of the ApoE genotype on brain macro- and
      microstructure, cognitive functioning and brain activity in fifty healthy young
      subjects (25 ApoE epsilon4 (epsilon4+) carriers and 25 non-carriers (epsilon4-),
      mean age 26.4+/-4.6years). We used diffusion tensor imaging (DTI) and voxel based
      morphometry (VBM) to assess brain structure, an extensive neuropsychological
      battery to test cognitive functioning and event-related functional magnetic
      resonance imaging (fMRI) to capture brain activity during episodic memory
      encoding and retrieval. ApoE epsilon4 carriers differed from non-carriers in fMRI
      activations but not in cognitive performance nor in brain micro- and
      macrostructure. These results suggest functional alterations in the episodic
      memory network that are modulated by the epsilon4 allele and might precede
      clinical or structural neurodegeneration. 

PMID- 24296332
TI  - Counseling women and men regarding exposures to reproductive and developmental
      toxicants before conception or women during pregnancy.
AB  - It should be apparent that determining the reproductive risks of an exposure
      during pregnancy or the cause of a child's congenital malformations is not a
      simple process. It involves a careful analysis of the medical and scientific
      literature pertaining to the reproductive toxic effects of exogenous agents in
      humans and animals, as well as an evaluation of the exposure and the biological
      plausibility of the concern of an increased risk or a causal connection between
      the exposure and a child's congenital malformations. It also involves having
      available a detailed physical examination of the malformed infant or child and a
      review of the scientific literature pertaining to genetic and environmental
      causes of the malformations in question. Abridged counseling on the basis of
      superficial and incomplete analyses is a disservice to the family. Experienced
      counselors understand that their primary task is to educate the pregnant women or
      family members concerning the risk of an environmental exposure. The counselor
      should advise them on the options available, but not on which option to select. 

PMID- 24296333
TI  - Pharmacogenomics related to growth disorders.
AB  - Growth disorders resulting in short stature are caused by a wide range of
      underlying pathophysiological processes. To improve height many of these
      conditions are treated with recombinant human growth hormone (rhGH). However,
      substantial inter-individual variability in growth response both in the short and
      long-term is recognised. Over the last decade, disease-specific growth prediction
      models have been developed that the clinician can use to define a child's
      potential response to rhGH and to optimise starting and maintenance doses of
      rhGH. These models, however, are not able to predict all the variations in
      treatment response. There has, therefore, been recent interest in using genetic
      information to contribute to the evaluation of responses to rhGH, including high
      throughput technologies for assessing DNA markers (genome) and mRNA transcripts
      (transcriptome) as pharmacogenomic tools. This review will focus on how these
      pharmacogenomic approaches are being applied to growth disorders.

PMID- 24296334
TI  - Combination of antithrombin and recombinant thrombomodulin attenuates leukocyte
      endothelial interaction and suppresses the increase of intrinsic damage
      associated molecular patterns in endotoxemic rats.
AB  - INTRODUCTION: Both antithrombin (AT) and thrombomodulin are key players in
      physiological anticoagulant systems. Because the levels of both factors are known
      to decrease significantly during severe sepsis, we hypothesized that a
      combination therapy would be effective. METHODS: A sepsis model was established
      using the intravenous infusion of lipopolysaccharide (LPS). A dose of 125 IU/kg
      of AT, 0.25 mg/kg of recombinant thrombomodulin, or a combination of both agents
      was injected immediately after LPS infusion (n = 7, each). Intravital observation
      of the mesenteric microcirculation was performed, and leukocyte adhesion and
      blood flow were calculated at 3 h after LPS infusion. Immediately after the
      observation, blood samples were obtained and coagulation markers, organ damage
      markers, the circulating levels of nucleosome and high-mobility group box 1 were
      measured. RESULTS: Microscopic findings revealed the suppression of leukocyte
      adhesion and thrombus formation in the combination group. The number of adhesive
      leukocytes on the endothelium was significantly suppressed (P < 0.01), and the
      blood flow in venules was better maintained in the combination group compared
      with the placebo control (P < 0.01). The blood samples showed the suppressed
      activation in coagulation, no significant changes were observed in the organ
      damage markers in the treatment groups. The circulating levels of nucleosome and
      high-mobility group box 1 were both decreased significantly in the combination
      group compared with the placebo control (P < 0.01). CONCLUSIONS: The
      coadministration of AT and recombinant thrombomodulin is effective for the
      suppression of leukocyte activation and cell death during sepsis.

PMID- 24296335
TI  - [Bilateral carotid dissection secondary to low-energy craniocervical trauma, with
      an excellent response following early endovascular treatment].

PMID- 24296336
TI  - [Hemodynamic monitoring in the critically patient. Recomendations of the
      Cardiological Intensive Care and CPR Working Group of the Spanish Society of
      Intensive Care and Coronary Units].
AB  - Hemodynamic monitoring offers valuable information on cardiovascular performance
      in the critically ill, and has become a fundamental tool in the diagnostic
      approach and in the therapy guidance of those patients presenting with tissue
      hypoperfusion. From introduction of the pulmonary artery catheter to the latest
      less invasive technologies, hemodynamic monitoring has been surrounded by many
      questions regarding its usefulness and its ultimate impact on patient prognosis.
      The Cardiological Intensive Care and CPR Working Group (GTCIC-RCP) of the Spanish
      Society of Intensive Care and Coronary Units (SEMICYUC) has recently impulsed the
      development of an updating series in hemodynamic monitoring. Now, a final series
      of recommendations are presented in order to analyze essential issues in
      hemodynamics, with the purpose of becoming a useful tool for residents and
      critical care practitioners involved in the daily management of critically ill
      patients. 

PMID- 24296342
TI  - Facial exercises for facial rejuvenation: a control group study.
AB  - OBJECTIVE: Facial exercises are a noninvasive alternative to medical approaches
      to facial rejuvenation. Logopedists could be involved in providing these
      exercises. Little research has been conducted, however, on the effectiveness of
      exercises for facial rejuvenation. This study assessed the effectiveness of 4
      exercises purportedly reducing wrinkles and sagging of the facial skin. METHOD: A
      control group study was conducted with 18 participants, 9 of whom (the
      experimental group) underwent daily training for 7 weeks. Pictures taken before
      and after 7 weeks of 5 facial areas (forehead, nasolabial folds, area above the
      upper lip, jawline and area under the chin) were evaluated by a panel of
      laypersons. In addition, the participants of the experimental group evaluated
      their own pictures. Evaluation included the pairwise presentation of pictures
      before and after 7 weeks and scoring of the same pictures by means of visual
      analogue scales in a random presentation. RESULTS: Only one significant
      difference was found between the control and experimental group. In the
      experimental group, the picture after therapy of the upper lip was more
      frequently chosen to be the younger-looking one by the panel. CONCLUSION: It
      cannot be concluded that facial exercises are effective. More systematic research
      is needed.

PMID- 24296343
TI  - Systemic therapy in squamous cell carcinoma of the vulva: current status and
      future directions.
AB  - OBJECTIVE: The advances achieved in the surgical management of vulvar squamous
      cell carcinoma (SCC) have not been mirrored in systemic therapy options. The
      objective of this paper is to summarize current evidence regarding systemic
      therapy in vulvar cancer, review the latest research on the biology of this
      disease, and identify future strategies to improve patient management. METHODS:
      MEDLINE and EMBASE were searched for all relevant English-language articles from
      inception to December 10, 2012. Existing evidence regarding systemic therapy in
      vulvar SCC was synthesized descriptively, with an emphasis on prospective studies
      when available. Single-patient case-reports were excluded. RESULTS: We identified
      12 studies of neoadjuvant chemoradiation, 8 studies of neoadjuvant chemotherapy
      alone, 18 studies of chemoradiation as primary therapy, 4 studies of chemotherapy
      in the adjuvant setting, and 8 studies of chemotherapy for recurrent or
      metastatic disease. Review of the biology of vulvar cancer was performed, and
      promising targets for the future were identified based on the two biologic
      pathways of disease development. New therapeutic strategies such as immune
      therapy and targeted agents hold promise for the future. CONCLUSIONS: Advances in
      systemic therapy for vulvar SCC are urgently needed, especially in the setting of
      recurrent and metastatic disease. A focus on the investigation of new targeted
      agents is encouraged and consideration of quality of life and sexual health
      issues is essential. International cooperation and adaptive trial designs are
      required to improve outcomes for this group of traditionally under-served women.

PMID- 24296344
TI  - Postoperative outcomes among patients undergoing thoracostomy tube placement at
      time of diaphragm peritonectomy or resection during primary cytoreductive surgery
      for ovarian cancer.
AB  - OBJECTIVE: Primary cytoreductive surgery in patients with stage IIIC-IV
      epithelial ovarian cancer frequently includes diaphragm peritonectomy or
      resection, which can lead to symptomatic pleural effusions when the resection
      specimen is >= 10 cm. Our objective was to evaluate whether the placement of an
      intraoperative thoracostomy tube decreased the incidence of symptomatic pleural
      effusions in these cases. METHODS: We identified 156 patients who underwent
      primary debulking surgery involving diaphragm peritonectomy or resection for
      stage III-IV ovarian cancer from 1/01-12/09. Using standard statistical tests,
      the incidence of symptomatic pleural effusions and other variables were compared
      between patients who did and did not have intraoperative chest tubes placed.
      RESULTS: Forty-nine patients had a resected diaphragm specimen >= 10 cm in
      largest dimension; 28 (57%) did not undergo chest tube placement (NCT group)
      while 21 (43%) did (CT group). Mediastinal lymph node dissection (0% vs 19%, P =
      0.028) and liver resections (11% vs 38%, P = 0.037) were higher in the CT group.
      Postoperatively, 57% of the NCT group developed a moderate or large pleural
      effusion compared to 19% of the CT group (P = 0.007). Thirteen patients (46%) in
      the NCT group developed respiratory symptoms requiring either placement of a
      postoperative chest tube or thoracentesis compared to 3 patients (14%) in the CT
      group (P = 0.018). CONCLUSIONS: Diaphragm peritonectomy or resection can often
      lead to moderate or large pleural effusions that may become symptomatic. In these
      patients, intraoperative chest tube placement may be considered to decrease the
      incidence of symptomatic effusions and the need for postoperative chest tube
      placement or thoracentesis.

PMID- 24296345
TI  - The value of re-exploration in patients with inadvertently morcellated uterine
      sarcoma.
AB  - OBJECTIVE: To describe the role of immediate re-exploration in patients with
      inadvertently morcellated uterine leiomyosarcoma (ULMS) and smooth muscle tumors
      of uncertain malignant potential (STUMP). METHODS: All patients with ULMS/STUMP
      who were managed or referred to the participating institutions from January 2005
      to January 2012 following minimally invasive gynecology surgery with morcellation
      were detected through the pathology database. The diagnosis was confirmed by
      gynecologic-pathologists following post-surgery pathology review. RESULTS: Twenty
      one patients with the diagnosis of ULMS (N = 15) and STUMP (N = 6) after
      morcellation were identified. The median age of occurrence was 46 years (range,
      25-58 years). Median follow-up duration was 27 months (range, 1.8-93.1 months).
      None of the 21 patients had documented evidence of extra-uterine disease at the
      time of original surgery. Ultimately 12 patients were immediately re-explored to
      complete staging. The median time to the staging surgery was 33 days (range 15
      118 days). Two (28.5%) out of seven patients with presumed stage I ULMS and one
      (25%) out of four patients with presumed stage I STUMP had significant findings
      of disseminated intraperitoneal disease detected at immediate surgical re
      exploration. One of the 8 patients with confined early ULMS and STUMP at the
      second surgery had intraperitoneal recurrence, while the remaining 7 patients
      have had no recurrence and remain disease free. CONCLUSION: Surgical re
      exploration is likely to show findings of disseminated peritoneal sarcomatosis in
      a significant number of patients diagnosed with ULMS after a morcellation
      procedure. Findings from re-exploration can contribute to the knowledge of
      natural history of morcellated ULMS/STUMP and allow for accurate prognostication.

PMID- 24296346
TI  - Host specificity of bacterial pathogens.
AB  - Most pathogens are able to infect multiple hosts but some are highly adapted to a
      single-host species. A detailed understanding of the basis of host specificity
      can provide important insights into molecular pathogenesis, the evolution of
      pathogenic microbes, and the potential for pathogens to cross the species barrier
      to infect new hosts. Comparative genomics and the development of humanized mouse
      models have provided important new tools with which to explore the basis of
      generalism and specialism. This review will examine host specificity of bacterial
      pathogens with a focus on generalist and specialist serovars of Salmonella
      enterica. 

PMID- 24296348
TI  - The role of MIZ-1 in MYC-dependent tumorigenesis.
AB  - A hallmark of MYC-transformed cells is their aberrant response to antimitogenic
      signals. Key examples include the inability of MYC-transformed cells to arrest
      proliferation in response to antimitogenic signals such as TGF-beta or DNA damage
      and their inability to differentiate into adipocytes in response to hormonal
      stimuli. Given the plethora of antimitogenic signals to which a tumor cell is
      exposed, it is likely that the ability to confer resistance to these signals is
      central to the transforming properties of MYC in vivo. At the same time, the
      inability of MYC-transformed cells to halt cell-cycle progression on stress may
      establish a dependence on mutations that impair or disable apoptosis. We propose
      that the interaction of MYC with the zinc finger protein MIZ-1 mediates
      resistance to antimitogenic signals. In contrast to other interactions of MYC,
      there is currently little evidence that MIZ-1 associates with MYC in normal,
      unperturbed cells. The functional interaction of both proteins becomes apparent
      at oncogenic expression levels of MYC and association with MIZ-1 mediates both
      oncogenic functions of MYC as well as tumor-suppressive responses to oncogenic
      levels of MYC. 

PMID- 24296347
TI  - Helicobacter and salmonella persistent infection strategies.
AB  - Some host-adapted bacterial pathogens are capable of causing persistent
      infections in humans. For example, Helicobacter pylori inhabits the human gastric
      mucosa and persistence can be lifelong. Salmonella enterica serovar Typhi causes
      systemic infections that involve colonization of the reticuloendothelial system
      and some individuals become lifelong carriers. In this review, I compare and
      contrast the different lifestyles of Helicobacter and Salmonella within the host
      and the strategies they have evolved to persist in mammalian hosts. Persistently
      infected carriers serve as the reservoirs for these pathogens, and the carrier
      state is an essential feature that is required for survival of the bacteria
      within a restricted host population. Therefore, investigating the chronic carrier
      state should provide insight into bacterial survival strategies, as well as new
      therapeutic approaches for treatments. 

PMID- 24296349
TI  - Roles for MYC in the establishment and maintenance of pluripotency.
AB  - MYC and MYCN have been directly implicated in the transcriptional regulation of
      several thousand genes in pluripotent stem cells and possibly contribute to the
      activity of all transcribed genes. Control of transcription by a pause-release
      mechanism, recruitment of positive and negative epigenetic regulators, and a
      general role in transcriptional amplification have all been implicated as part of
      the broad, overarching mechanism by which MYC controls stem cell biology. As
      would be anticipated from the regulation of so many genes, MYC is involved in a
      wide range of cellular processes including cell-cycle control, metabolism, signal
      transduction, self-renewal, maintenance of pluripotency, and control of cell fate
      decisions. MYC transcription factors also have clear roles in cell reprogramming
      and establishment of the pluripotent state. The mechanism by which MYC
      accomplishes this is now being explored and promises to uncover unexpected facets
      of general MYC regulation that are likely to be applicable to cancer biology. In
      this work we review our current understanding of how MYC contributes to the
      maintenance and establishment of pluripotent cells and how it contributes to
      early embryonic development. 

PMID- 24296350
TI  - Microbial ecology of the skin in the era of metagenomics and molecular
      microbiology.
AB  - The skin is the primary physical barrier between the body and the external
      environment and is also a substrate for the colonization of numerous microbes.
      Previously, dermatological microbiology research was dominated by culture-based
      techniques, but significant advances in genomic technologies have enabled the
      development of less-biased, culture-independent approaches to characterize skin
      microbial communities. These molecular microbiology approaches illustrate the
      great diversity of microbiota colonizing the skin and highlight unique features
      such as site specificity, temporal dynamics, and interpersonal variation.
      Disruptions in skin commensal microbiota are associated with the progression of
      many dermatological diseases. A greater understanding of how skin microbes
      interact with each other and with their host, and how we can therapeutically
      manipulate those interactions, will provide powerful tools for treating and
      preventing dermatological disease. 

PMID- 24296351
TI  - Lessons and limits of mouse models.
AB  - Seminal studies in rabbits and rodent transplantation models by Peter Medawar
      revealed that cellular processes, rather than humoral antibodies, are central to
      the acute rejection of transplanted organs, and much of basic transplantation
      research continues to be focused on the biology and control of these cells, which
      were subsequently shown to be T cells. However, the success of current
      immunosuppression at controlling T-cell-mediated rejection has resulted in an
      increasing awareness of antibody-mediated rejection in the clinic. This, in turn,
      has fueled an emerging interest in the biology of allospecific antibodies, the B
      cells that produce these antibodies, and the development of mouse models that
      allow their investigation. Here we summarize some of the more widely used mouse
      models that have been developed to study the immunobiology of alloreactivity,
      transplantation rejection and tolerance, and used to identify therapeutic
      strategies that modulate these events. 

PMID- 24296352
TI  - T-cell costimulatory blockade in organ transplantation.
AB  - Before it became possible to derive T-cell lines and clones, initial
      experimentation on the activation requirements of T lymphocytes was performed on
      transformed cell lines, such as Jurkat. These studies, although technically
      correct, proved misleading as most transformed T cells can be activated by
      stimulation of the clonotypic T-cell receptor (TCR) alone. In contrast, once it
      became possible to study nontransformed T cells, it quickly became clear that TCR
      stimulation by itself is insufficient for optimal activation of naive T cells,
      but in fact, induces a state of anergy. It then became clear that functional
      activation of T cells requires not only recognition of major histocompatibility
      complex (MHC) and peptide by the TCR, but also requires ligation of costimulatory
      receptors expressed on the cell surface. 

PMID- 24296355
TI  - Low-density plating is sufficient to induce cardiac hypertrophy and electrical
      remodeling in highly purified human iPS cell-derived cardiomyocytes.
AB  - INTRODUCTION: Cardiac hypertrophy is a leading cause of many cardiovascular
      diseases, including heart failure, but its pathological mechanism is not fully
      understood. This study used highly purified human induced pluripotent stem cell
      (hiPSC)-derived cardiomyocytes to produce an in vitro hypertrophy model and
      characterize its gene expression and electrophysiological properties. METHODS:
      For 7 days we cultured hiPSC-derived cardiomyocytes plated at high (2800-4800
      cells/mm(2)) or low (500-1200 cells/mm(2)) cell density and assessed their cell
      size with confocal and fluorescence microscopy, their electrophysiological and
      pharmacological responses with multi-electrode array systems, and their gene
      expression patterns by using DNA microarray technology and quantitative PCR. We
      used quantitative PCR and Western blotting to compare the expression of potassium
      channel genes between the hiPSC-derived cardiomyocytes and human fetal and adult
      hearts. RESULTS: The hiPSC-derived cardiomyocytes showed spontaneous beating and
      similar pattern of alpha-actinin molecules regardless of plating density.
      However, cells plated at low density had the following characteristics compared
      with those at high density: 1) significant enlargement in size; 2) significant
      increase or decrease in expression of the cardiac hypertrophy-characteristic
      genes NPPA, ATP2A2, ANKRD1 and MYL2 in accordance with the progression of
      hypertrophy; 3) significant reduction in responses to the inhibitors of cardiac
      slow delayed-rectifier K(+) current (IKs), chromanol 293B and HMR1556, in a cell
      density-dependent manner; and 4) significant reduction in the expression of the
      KCNQ1 and KCNJ2 genes coding the K(+) ion channels conducting each IKs and
      cardiac inward rectifier outward K(+) current (IK1). DISCUSSION: The enlargement,
      hypertrophy-characteristic and potassium ion channels gene expression of hiPSC
      derived cardiomyocytes suggest that low-density plating was sufficient to induce
      cardiac hypertrophy. This model may be useful in elucidating mechanisms
      underlying the onset and progress of cardiac hypertrophy, because these cells can
      be cultured for several weeks.

PMID- 24296353
TI  - Cutaneous Notch signaling in health and disease.
AB  - The development and maintenance of the skin are dependent on myriad signaling
      pathways that regulate a variety of cellular processes. In cutaneous epithelial
      cells, the Notch cascade plays a central role in ensuring that proliferation and
      differentiation are coordinated appropriately, a function that it imparts during
      both ontogeny and homeostasis. Aberrations of the Notch signaling pathway result
      in severe abnormalities in the epidermis and its appendages and cause functional
      defects such as perturbed barrier function. In addition, impaired Notch signaling
      is associated with diseases of the skin such as atopy and cancer. The pathology
      associated with aberrant cutaneous Notch signaling reflects the complex
      mechanisms underpinning its function in this tissue and involves both cell
      autonomous and nonautonomous mechanisms. This review summarizes our current
      knowledge of the role of Notch signaling in the skin during health and disease. 

PMID- 24296356
TI  - The proton-activated receptor GPR4 modulates glucose homeostasis by increasing
      insulin sensitivity.
AB  - BACKGROUND: The proton-activated G protein-coupled receptor GPR4 is expressed in
      many tissues including white adipose tissue. GPR4 is activated by extracellular
      protons in the physiological pH range (i.e. pH 7.7 - 6.8) and is coupled to the
      production of cAMP. METHODS: We examined mice lacking GPR4 and examined glucose
      tolerance and insulin sensitivity in young and aged mice as well as in mice fed
      with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines
      in white adipose tissue, liver and skeletal muscle was assessed. RESULTS: Here we
      show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance
      test and increased insulin sensitivity. Insulin levels were comparable but leptin
      levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of
      PPARa, IL-6, IL-10, TNFa, and TGF-1b in skeletal muscle, white adipose tissue,
      and liver. High fat diet abolished the differences in glucose tolerance and
      insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice
      (12 months old), the positive effect of GPR4 deficiency on glucose tolerance and
      insulin sensitivity was maintained. Liver and adipose tissue showed no major
      differences in the mRNA expression of pro- and anti-inflammatory factors between
      aged mice of both genotypes. CONCLUSION: Thus, GPR4 deficiency improves glucose
      tolerance and insulin sensitivity. The effect may involve an altered balance
      between pro- and anti-inflammatory factors in insulin target tissues.

PMID- 24296357
TI  - A clinical survey on the prevalence and types of cheek teeth disorders present in
      400 Zamorano-Leones and 400 Mirandes donkeys (Equus asinus).
AB  - Dental disease is now recognised as a major but often unrecognised disorder of
      equids, including horses and donkeys. However, very few large clinical studies
      have documented the prevalence and type of dental disease present in different
      equid populations and no dental studies have been reported in Zamorano-Leones or
      Mirandes donkeys, two endangered donkey breeds. Clinical and detailed oral
      examinations were performed in 400 Mirandes and 400 Zamorano-Leones donkeys in
      Portugal and Spain. It was found that just 4.5 per cent had ever received any
      previous dental care. Cheek teeth (CT) disorders were present in 82.8 per cent of
      these donkeys, ranging from a prevalence of 29.6 per cent in the <2.5-year-old
      group to 100 per cent in the >25-year-old group. These CT disorders included
      enamel overgrowths (73.1 per cent prevalence but with just 6.3 per cent having
      associated soft tissue injuries), focal overgrowths (37.3 per cent), periodontal
      disease (23.5 per cent) and diastemata (19.9 per cent). Peripheral caries was
      present in 5.9 per cent of cases, but inexplicably, infundibular caries was very
      rare (1.3 per cent prevalence); this may have been due to their almost fully
      foraged diet. The high prevalence of enamel overgrowths in these donkeys, most
      which never received concentrates, also raises questions about the aetiology of
      this disorder. This very high prevalence of CT disorders, especially in older
      donkeys, was of great welfare concern in some cases and emphasises the need for
      routine dental care in these cases on welfare grounds and in order to help
      preserve these unique breeds. 

PMID- 24296358
TI  - The evidence for pain-related cognitive impairment.

PMID- 24296359
TI  - Ischemic Stroke as a Complication of Varicella Zoster Encephalitis: A Case Report
      With Detailed EEG Discussion.
AB  - A 72-year-old man with varicella zoster virus (VZV) encephalitis complicated by
      an ischemic stroke in the right internal capsule, possibly due to secondary small
      vessel vasculopathy, is described in this case report. The focus of this article
      is on the electroencephalogram (EEG) description of varicella zoster encephalitis
      and secondary vasculopathy because EEG descriptions are scarce in the literature
      and detailed descriptions are lacking. In this patient's EEG, right temporal
      theta waves were found in combination with a mild slowing of the background
      rhythm to 7.5 to 8 Hz in the acute stage with an amplitude asymmetry (right
      temporal lobe amplitudes were significantly higher compared with the left side).
      The theta waves were thought to originate from the ischemic lacunar stroke, the
      slowing of the background rhythm from early encephalitis, and the amplitude
      asymmetry was presumed to be of physiologic origin. A follow-up EEG 6 days after
      initiation of treatment with acyclovir showed a normal symmetrical background
      rhythm of 8 to 8.5 Hz, wherein the theta waves were significantly reduced in
      abundance, and the amplitude asymmetry was unchanged. In conclusion, the EEG may
      localize focal abnormalities possibly due to cortical or lacunar ischemia, which
      could be explained by early small and/or large vessel vasculopathy in patients
      with suspected VZV encephalitis.

PMID- 24296360
TI  - Association of a paraneoplastic motor neuron disease with anti-Ri antibodies and
      a novel SOD1 I18del mutation.
AB  - INTRODUCTION: Whether motor neuron diseases (MNDs) can be considered in some
      cases of paraneoplastic syndromes is controversial. We report a case of rapidly
      progressive motor neuronopathy following a diagnosis of breast carcinoma, with a
      presence of anti-Ri antibodies, and a novel SOD1 gene mutation. OBSERVATION: An
      80-year-old woman with mucinous adenocarcinoma of the left breast for 4 years
      developed sub-acute quadriparesis. Myography revealed chronic denervation signs.
      The patient had serum anti-Ri onconeural antibodies. The diagnosis of
      paraneoplastic MND was established. Because of a familial history of ALS, a
      genetic analysis for familial ALS was performed. We identified a novel
      heterozygous mutation in SOD1 gene, SOD I18del. This mutation may reflect a
      genetic predisposition to develop a MND, inducing fragility of motor neurons.
      Neurological improvement was observed after three months of both intravenous
      gamma globulin and corticosteroids. CONCLUSION: The present observation supports
      the idea that MND can be considered as a paraneoplastic syndrome. A combination
      of anti-Ri onconeural antibodies and a particular SOD1 gene mutation, consisting
      in risk factor, might be in cause in the process of motor neuron death. When in
      doubt, paraneoplastic cause should be suspected in the differential diagnosis of
      MND. Immunotherapy treatment may lead to a favorable outcome.

PMID- 24296361
TI  - Gene expression profile in fibroblasts of Huntington's disease patients and
      controls.
AB  - Huntington's disease is an inherited disorder caused by expanded stretch of
      consecutive trinucleotides (cytosine-adenosine-guanine, CAG) within the first
      exon of the huntingtin (HTT) gene on chromosome 4 (p16.3). The mutated huntingtin
      (mHTT) gains toxic function, probably through mechanisms that involve aberrant
      interactions in several pathways, causing cytotoxicity. Pathophysiology of
      disease involves several tissues; indeed it has been shown that there is a broad
      toxic effect of mHTT in the peripheral tissue of patients with HD, not only in
      the central nervous system. In this study we compared gene expression profiles
      (GEP) of HD fibroblasts and matched controls using microarray technology. We used
      RT-PCR to test the consistency of the microarray data and we found four genes up
      regulated in HD patients with respect to control individuals. The genes appear to
      be involved in different pathways that have been shown to be perturbed even in HD
      models and patients. Although our study is preliminary and has to be extended to
      a larger cohort of HD patients and controls, nevertheless it shows that gene
      expression profiles seem to be altered in the fibroblasts of HD patients.
      Validation of the differential expressions at the protein level is required to
      ascertain if this cell type can be considered a suitable model for the
      identification of HD biomarkers. 

PMID- 24296362
TI  - Overactive bladder and pontine reticular formation.
AB  - BACKGROUND: The etiology of overactive bladder (OAB) remains unclear. Observed
      neurogenic factors in the literature are limited to suprapontine or spinal
      pathologies. The blink reflex is a useful tool in the evaluation of brainstem
      functions. Blink reflex latency times were evaluated in order to reveal pathology
      in the brainstem. METHODS: A total of 60 women, 30 patients with idiopathic OAB
      and 30 healthy controls, were enrolled in the study. Blink reflex latency times
      were analyzed by electrical stimulation of the supraorbital nerve. Two responses
      in the orbicularis oculi muscle, early ipsilateral response (R1) and late
      bilateral response (R2) latency times, were recorded. RESULTS: Mean ages of the
      patients and controls were 51.9 +/- 5.3 and 49.2 +/- 6.2 years, respectively. R2
      latency times were significantly higher in patients than in controls. However, R1
      latency times were similar between the two groups. CONCLUSIONS: The results of
      the study suggest a significant relation between late blink latency times and
      OAB. An oligosynaptic path via the trigeminal nuclei is responsible for R1;
      however, R2 response is relayed through the reticular formation. Stimulation of
      pontine reticular formation inhibits micturition contraction. In some patients,
      idiopathic OAB may result from reticular formation-originated pathology.
      Additional studies on other reticular formation-mediated reflexes are needed to
      reveal possible dysfunction of reticular formation.

PMID- 24296364
TI  - Survival and neurodevelopmental outcome of preterm infants born at 22-24 weeks of
      gestational age.
AB  - BACKGROUND: The limits of viability in extremely premature infants are
      challenging for any neonatologists in developed countries. The neurological
      development and growth of extremely preterm infants have come to be the emerging
      issue following the management in the neonatal intensive care unit. OBJECTIVE: To
      assess potential associations between changes in practice and
      survival/neurodevelopmental outcome, and clinical outcomes of extremely preterm
      infants born at the limit of viability studied in a tertiary center. STUDY
      DESIGN: A retrospective study enrolled 51 infants who had no congenital
      disorders, and were born at 22-24 weeks of gestational age (GA) in 2000-2009 in
      our institution. Clinical variables and interventions were studied with regard to
      one-year survival and developmental quotient (DQ) at 3 years of age. RESULTS: The
      one-year survival rate of 24 preterm infants born in 2005-2009 (79%) was higher
      than that of the 27 infants born in 2000-2004 (52%, p = 0.04). Infants born after
      2005 underwent less tocolysis (54 vs. 94%, p < 0.01) and more frequently
      antenatal steroid therapy (32 vs. 6%, p = 0.01) than those born before 2004. The
      post-2005 survivors (n = 19) received more frequently indomethacin therapy (89
      vs. 50%, p = 0.03) and early parenteral nutrition (95 vs. 36%, p < 0.01) than the
      pre-2004 survivors (n = 14). There were no differences in the proportion of
      infants who attained a DQ of >50 at 3 years of age between pre-2004 (9/13, 69%)
      and post-2005 groups (10/17, 59%). Multivariate analysis indicated that extremely
      premature birth at GA <24 weeks was the sole critical factor for a DQ of >50 in
      survivors. CONCLUSIONS: The perinatal care after 2005 improved the overall
      survival rate, but not the neurological outcome of preterm survivors at the limit
      of viability. Neurodevelopmental impairments were associated with extremely
      premature birth at GA <24 weeks.

PMID- 24296365
TI  - Novel acid-labile subunit ( IGFALS ) mutation p.T145K (c.434C>A) in a patient
      with ALS deficiency, normal stature and immunological dysfunction.
AB  - We report a novel missense mutation p.T145K in the insulin-like growth factor
      (IGF) acid-labile subunit (IGFALS) gene identified in a Turkish patient with
      normal growth, transient pancytopenic episodes and signs of immunological
      dysfunction. Because of recurrent cutaneous mycoses and absence of pubertal
      development until the age of 14.75 years we determined several endocrine
      parameters in order to rule out autoimmune-polyendocrine syndromes. Despite a
      normal height between the 25th and 50th percentile we found severely decreased
      IGF-1 and undetectably low IGFBP-3 levels. Laboratory signs of immunological
      dysfunction included reduced total lymphocyte count with diminished B and T
      helper cell fractions, decreased serum concentrations of IgM and IgG subclass 4,
      and elevated antinuclear antibody and anti-dsDNA titers as well as persistently
      high interleukin-2-receptor levels. Further endocrine work-up revealed elevated
      fasting insulin and undetectably low ALS serum levels, leading to the diagnosis
      of ALS deficiency. Sequencing of the coding region of the IGFALS gene showed a
      novel homozygous missense mutation (c.434C>A; p.T145K). Since immunological
      abnormalities have not been reported in more than 20 ALS-deficient patients so
      far and our patient was born to consanguineous parents, a second autosomal
      recessive defect is likely to underlie the immunological phenotype, although a
      causative role of IGFALS p.T145K cannot be entirely ruled out.

PMID- 24296366
TI  - Positive correlation between baseline PET or PET/CT findings and clinical
      parameters in multiple myeloma patients.
AB  - Recently, positron emission tomography (PET) has been incorporated into a series
      of prospective studies as a predictor of outcomes in multiple myeloma (MM), and
      the number of (18)F-fluorodeoxuglucose (FDG)-avid focal lesions (FLs) and the
      intensity of tumor metabolism have been designated as important surrogate markers
      for predicting prognosis. Here, we compared initial clinical characteristics of
      MM patients with baseline PET parameters: the number of FLs and the maximum
      standardized uptake value (SUVmax). A total of 59 patients diagnosed with MM
      between August 2004 and February 2012 were reviewed. At diagnosis, 23 patients
      (40.0%) had <=3 FLs, 11 patients (18.6%) 4-9 FLs, and 25 patients (42.4%) >=10
      FLs. The median SUVmax was 5.3 (range 0-24.3), and 40 patients (67.8%) showed a
      SUVmax >4. No clinical characteristics were significantly different between
      groups with a SUVmax <=4 and a SUVmax >4. However, there were significant
      differences in several clinical indices between the FLs <=3 and FLs >3 groups;
      elevated beta2-microglobulin, elevated lactate dehydrogenase, anemia and more
      advanced disease by the Durie-Salmon stage corresponded to FLs >3 at baseline
      PET. Adverse baseline PET findings are positively correlated with prognostically
      relevant clinical parameters. Regarding PET parameters, FLs are more likely to be
      well correlated with disease aggressiveness and pathophysiology compared to
      SUVmax.

PMID- 24296368
TI  - Optic disc edema from papilledema.

PMID- 24296367
TI  - Epidemiology and risk factors for idiopathic intracranial hypertension.

PMID- 24296369
TI  - Obesity and the role of nonsurgical and surgical weight reduction in idiopathic
      intracranial hypertension.

PMID- 24296370
TI  - Optic nerve sheath fenestration: indications, techniques, mechanisms and,
      results.

PMID- 24296371
TI  - Cerebrospinal fluid diversion procedures in the treatment of patients with
      idiopathic intracranial hypertension.

PMID- 24296372
TI  - Cerebral venous sinus thrombosis and stenosis in pseudotumor cerebri syndrome.

PMID- 24296373
TI  - Posterior scleral biomechanics and the translaminar pressure difference.

PMID- 24296374
TI  - Compartmentalized cerebrospinal fluid.

PMID- 24296375
TI  - Headache management in idiopathic intracranial hypertension.

PMID- 24296376
TI  - Neuro-ophthalmic manifestations in adult hydrocephalus.

PMID- 24296378
TI  - Intracranial pressure and the eye. Preface.

PMID- 24296379
TI  - Biomarkers in acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: The article provides an overview of efforts to identify and
      validate biomarkers in acute respiratory distress syndrome (ARDS) and a
      discussion of the challenges confronting researchers in this area. RECENT
      FINDINGS: Although various putative biomarkers have been investigated in ARDS,
      the data have been largely disappointing and the 'troponin' of ARDS remains
      elusive. Establishing a relationship between measurable biological processes and
      clinical outcomes is vital to advancing clinical trials in ARDS and expanding our
      arsenal of treatments for this complex syndrome. SUMMARY: This article summarizes
      the current status of ARDS biomarker research and provides a framework for future
      investigation.

PMID- 24296381
TI  - A plea to my colleagues in the cardiovascular space: it's time to lock arms.

PMID- 24296380
TI  - Quality of life assessment for acute heart failure patients from emergency
      department presentation through 30 days after discharge: a pilot study with the
      Kansas City Cardiomyopathy Questionnaire.
AB  - BACKGROUND: There are no well validated patient-reported disease status
      instruments for acute heart failure (HF). We assessed the feasibility of using
      the Kansas City Cardiomyopathy Questionnaire (KCCQ) during acute heart failure
      hospitalization, and the association of acute changes with 30-day readmission.
      METHODS AND RESULTS: A convenience sample of acute HF patients were administered
      the KCCQ on presentation, discharge, and 30 days after discharge. We examined
      mean differences in KCCQ scores over time, and we stratified by readmission
      status to examine differences in hospital-based changes with the use of t test
      and logistic regression. Among 52 patients (mean age 63 +/- 35 years, 56.9% male,
      46.2% white), discharge and 30-day assessments were each completed by 90%. Scores
      were lowest at presentation, improved during hospitalization, and were highest at
      30 days. The mean change was +11.9 +/- 97.0 (P = .007) between presentation and
      discharge and +19.8 +/- 87.8 (P < .001) between discharge and 30 days. Within the
      30-day follow-up, 10 patients were readmitted, and there were no significant
      differences in score changes during hospitalization between patients with and
      without readmission (readmitted patients: +4.8 +/- 81.5 vs no readmission +16.2
      +/- 27.4; P = .32). CONCLUSIONS: In this pilot study, the KCCQ is feasible to use
      during acute HF hospitalizations and demonstrates sensitivity to acute changes,
      but score changes during hospitalization did not predict 30-day readmission.

PMID- 24296382
TI  - Thrombolysis followed by coronary angiography versus primary percutaneous
      coronary intervention in non-anterior ST-elevation myocardial infarction.
AB  - BACKGROUND: Previous studies demonstrated the superiority of primary percutaneous
      coronary intervention (PCI) over thrombolysis for treatment of ST-elevation
      myocardial infarction (STEMI); however, this advantage is less evident in low
      risk populations. The aim of this study was to assess whether a strategy of
      thrombolysis followed by routine coronary angiography in patients with non
      anterior STEMI is non-inferior to primary PCI. METHODS: Consecutive patients with
      non-anterior STEMI presenting within 6 hours of symptom onset who received
      reperfusion treatment were included. Mortality, infarct size, and in-hospital and
      long-term major adverse events were compared between patients treated with
      primary PCI to those who received thrombolysis followed by coronary angiography
      and intervention as needed. RESULTS: A total of 300 patients were included: 180
      who received thrombolysis and 120 treated with primary PCI. No significant
      differences were found in mortality, infarct size, or long-term adverse events
      between groups. Higher rates of in-hospital recurrent ischemic events and longer
      hospitalization were noted in the thrombolysis group. CONCLUSIONS: The strategy
      of thrombolysis followed by routine coronary angiography in non-anterior STEMI
      patients results in major outcomes similar to primary PCI. Thrombolysis serves as
      a viable approach for patients presenting with non-anterior STEMI to hospitals
      without catheterization facilities. The optimal time between thrombolysis and
      coronary angiography should be within 2 days to avoid recurrent ischemia.

PMID- 24296383
TI  - Stent loss and retrieval during percutaneous coronary interventions: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: We present a systematic review and meta-analysis of the frequency,
      consequences, and treatment of stent loss during percutaneous coronary
      intervention (PCI). BACKGROUND: Stent loss during PCI has received limited study.
      METHODS: We conducted a meta-analysis of 18 case series and 45 case reports
      published between 1991 and 2012 on stent loss during PCI. Data on the frequency
      of stent loss, treatment strategies, and clinical outcomes were collected.
      RESULTS: A total of 1048 stents were lost in 968 PCIs. Stent loss occurred in 919
      of 71,655 PCIs (1.3%; 95% confidence interval, 0.8%-2.8%). The incidence of stent
      loss in studies published before 2000, between 2000 and 2005, and after 2005 was
      5%, 1%, and 0.3%, respectively (P<.001). Of the 1048 lost stents, 698 (66%) were
      successfully retrieved from the coronary circulation, 130 (12%) were deployed, 27
      (3%) were crushed, and 28 (3%) were left untreated; treatment of 165 stents (16%)
      was not reported. A complication occurred in 171 patients (19%), of whom 98 (57%)
      had coronary artery bypass graft surgery, 31 (18%) myocardial infarction, 33
      (19%) died, 10 (6%) had bleeding requiring transfusion, 5 (3%) had vascular
      access complications, and 1 patient (0.6%) had a cerebrovascular accident (some
      patients had more than one event). CONCLUSIONS: The incidence of stent loss
      during PCI is low and has been decreasing. Although the lost stents were
      successfully retrieved in most cases, stent loss was associated with high rates
      of complications, such as coronary artery bypass graft surgery, myocardial
      infarction, and death.

PMID- 24296384
TI  - In vitro assessment of mathematically-derived fractional flow reserve in coronary
      lesions with more than two sequential stenoses.
AB  - BACKGROUND: Myocardial fractional flow reserve (FFR) is a reliable index in
      coronary intervention. A simple FFR measurement does not predict the true
      functional severity of an individual stenosis in multiple sequential coronary
      stenoses because of complex interaction between the stenoses. Application of the
      theoretical equations to predict the true FFR of individual stenosis is limited
      in a tandem lesion. Two novel equations applicable to a multiple sequential
      coronary stenoses are mathematically derived. One predicts the true FFR of each
      stenosis (equation A), and the other predicts the true FFR after releasing a
      given stenosis (equation B). The present study aimed to validate the two derived
      equations in an in vitro model of coronary circulation. METHODS AND RESULTS:
      Predictive FFR was compared with true FFR in an in vitro model of three
      sequential stenoses using linear regression analysis. The difference between
      apparent FFR and true FFR was compared with the difference between predictive FFR
      and true FFR. The legitimacy of equation A was first assessed. A close
      correlation was found between predictive FFR and true FFR (r2 = 0.92). The
      difference between predictive FFR and true FFR was significantly lower compared
      to the difference between apparent FFR and true FFR (0.18 +/- 0.10 vs 0.05 +/-
      0.05; P<.001). The legitimacy of equation B was also assessed, and a close
      correlation was found (r2 = 0.97). The difference was significantly lower when we
      applied equation B (0.13 +/- 0.06 vs 0.04 +/- 0.02; P<.001). CONCLUSIONS:
      Equations A and B strongly predict the true value of FFR in the experimental
      model of coronary circulation.

PMID- 24296385
TI  - Global risk score for choosing the best revascularization strategy in patients
      with unprotected left main stenosis.
AB  - BACKGROUND: Coronary artery bypass graft (CABG) is recommended for patients with
      unprotected left main stenosis (ULMS). Percutaneous coronary intervention (PCI)
      is only recommended in specific anatomic conditions as in patients with low/mid
      SYNTAX score (SS). The aim of this study was to assess if the clinical and
      anatomic global risk classification (GRC) can enhance the indication of both
      revascularization therapies. METHODS: A total of 407 patients with ULMS treated
      with CABG (n = 285) or PCI (n = 122) were prospectively collected. The decision
      to treat with CABG or PCI was dependent on patient and physician's choice.
      Patients with ST-elevation myocardial infarction, shock, or valve disease were
      excluded. Clinical follow-up was obtained at 3 years. RESULTS: Patients with low
      GRC (n = 151) treated with CABG vs those with PCI had similar cardiac mortality
      (5.9% vs 0%, respectively; P=.17) and major adverse cardiac events (MACE; 18.5%
      vs 12.5%, respectively; P=.40). Patients classified as mid GRC (n = 175) had
      similar cardiac death (11.1% vs 10.3%; P=.85) and MACE rates (20.7% vs 22.4%;
      P=.92) with CABG or PCI, respectively. Patients with high GRC (n = 81) treated
      with CABG had numerically fewer cardiac deaths (16.3% vs 28.1%; P=.16) and lower
      MACE rates (24.5% vs 40.6%; P=.048) than with PCI. Statistical models using the
      GRC as a predictor of cardiac death showed better goodness-of-fit than the SS.
      CONCLUSION: Patients with low/mid GRC have similar mid-term outcomes with either
      CABG or PCI; patients with high GRC seem to benefit from CABG. Although further
      investigations are required, GRC is a better predictor of outcomes than SS.

PMID- 24296386
TI  - Does the target vessel impact on results of percutaneous coronary intervention
      for bifurcation lesions? insights from the I-BIGIS Registry.
AB  - BACKGROUND: Bifurcations remain a challenging subset for percutaneous coronary
      intervention (PCI). Specifically, it is unclear whether bifurcations on left
      anterior descending (LAD) coronary arteries have the same prognosis of
      bifurcations on left circumflex (LCX) or right coronary arteries (RCA). We
      compared the results of PCI for bifurcation lesions, focusing on target vessel.
      METHODS: Patients undergoing bifurcation PCI on the LAD were compared to those
      undergoing bifurcation PCI on the LCX and on the RCA. The primary endpoint was
      the long-term major adverse cardiac event (MACE) rate, defined as death,
      myocardial infarction, or target lesion revascularization (TLR). RESULTS: A total
      of 2376 subjects were included, with 71.1% treated on the LAD, 21.5% on the LCX,
      and 7.4% on the RCA. Early MACE rates were similarly uncommon in the LAD (2.0%),
      RCA (2.3%), or LCX (1.2%) groups (P=.46). Long-term outcomes (22.81 +/- 2.7
      months) were also similar, with MACE in 12.6%, 14.9%, and 12.4% (P=.39), death in
      4.0%, 4.5%, and 4.5% (P=.83), myocardial infarction in 3.8%, 3.6%, and 3.0%
      (P=.23), and stent thrombosis in 1.5%, 2.2%, and 1.7% (P=.64), despite an
      apparent increase in TLR rates in the LCX group (12.4%) vs LAD (8.9%) or RCA
      (7.3%) groups (P=.04). However, after multivariable adjustment, the risk of all
      long-term adverse events was similar irrespective of target vessel. CONCLUSIONS:
      Bifurcations localized in the LCX and RCA are associated with event rates at
      least as high as those in the LAD. Thus, care should be taken to skillfully
      perform PCI and maximize post-PCI medical therapy wherever the bifurcation lesion
      is located.

PMID- 24296387
TI  - Safety and effectiveness of the Genous endothelial progenitor cell-capture stent:
      follow-up to 5 years.
AB  - AIMS: To evaluate the long-term clinical outcomes following percutaneous coronary
      intervention (PCI) with the Genous stent in an unselected population. METHODS:
      All patients admitted to a single center who underwent PCI using the GS
      exclusively, between May 2006 and May 2012, were enrolled, and a clinical follow
      up of up to 60 months was carried out. The primary endpoint of major adverse
      cardiac event (MACE) rate was defined as the composite of cardiac death, acute
      myocardial infarction (AMI), and target lesion revascularization (TLR). RESULTS:
      Of the 450 patients included (75.1% male; 65.5 +/- 11.7 years), 28.4% were
      diabetic and acute coronary syndrome was the reason for PCI in 76.4%. Angioplasty
      was performed in 524 lesions using 597 Genous stents, with angiographic success
      in 97.1%. At a median of 36 months of follow-up (range, 1-75 months), MACE, AMI,
      TLR, stent restenosis (SR), and stent thrombosis (ST) rates were 15.6%, 8.4%,
      4.4%, 3.8%, and 2.2%, respectively. Between 12 and 24 months, the TLR, SR, and ST
      rates practically stabilized, up to 60 months. Bifurcation lesions were
      independently associated with MACE, TLR, and SR. CONCLUSION: This is the first
      study reporting clinical results with the Genous stent up to 60 months. The
      Genous stent was safe and effective in the long-term, in an unselected
      population.

PMID- 24296388
TI  - Long-term outcomes of the Viabahn stent in the treatment of in-stent restenosis
      in the superficial femoral artery.
AB  - There is no universally accepted method to treat in-stent restenosis (ISR) in the
      superficial femoral artery (SFA). It is hypothesized that using the Viabahn
      expandable polytetrafluoroethylene- covered stent to treat ISR may prevent tissue
      infiltration and intimal hyperplasia that leads to restenosis. METHODS: We
      studied 22 patients (27 limbs) referred for treatment of severe ISR of the SFA.
      All patients were treated with the Viabahn stent implanted in the restenotic
      segments. We also analyzed several demographic, procedural, and laboratory
      parameters that could potentially be predictors of Viabahn restenosis. RESULTS:
      Among patients treated, 63% had severe claudication and 37% had critical limb
      ischemia. Mean treated lesion length was 214.8 +/- 87.2 mm, mean run-off score
      was 3.9 +/- 2.8. Mean follow-up period was 21.8 +/- 10.3 months. Ten patients
      (37%) developed Viabahn restenosis. The mean lesion length was 180.0 +/- 107.9 mm
      in the restenosis group and 219.4 +/- 78.9 mm in the no-restenosis group (P=.27).
      There was no significant difference between the two groups in the rest of
      demographic, procedural, and laboratory parameters. In 90%, restenosis occurred
      within the first 12 months and the remaining 10% occurred within 14 months. The
      mean time to restenosis was 6.2 +/- 4.3 months. We observed no Viabahn ISR
      occurring after 14 month of follow-up. CONCLUSION: The Viabahn stent can be used
      to treat ISR in the SFA, with favorable results of 63% primary patency at up to 3
      years of follow-up. Analysis of multiple factors showed no association with
      restenosis occurrence. If the Viabahn remained patent for 14 months, the
      likelihood of restenosis was low.

PMID- 24296389
TI  - Ultrasound-guided radial artery access by a non-ultrasound trained interventional
      cardiologist improved first-attempt success rates and shortened time for
      successful radial artery cannulation.
AB  - BACKGROUND: Use of the radial artery for cardiac catheterization and percutaneous
      coronary intervention (PCI) continues to expand. Cannulating the radial artery
      can be one of the most challenging aspects of the radial approach. Ultrasound
      guided vascular access may be a method to improve first-attempt success rates and
      shorten time to radial artery access. METHODS: Fifty consecutive patients
      underwent ultrasound-guided radial artery access (UGRAA) by a senior
      interventional cardiologist with little prior experience with UGRAA. The operator
      had 20 run-in cases before enrolling subjects. Time to establish access and
      number of attempts required for each patient were recorded. Ultrasound was also
      used to measure radial arterial diameter and the distance between the skin and
      the anterior wall of the radial artery. RESULTS: All patients had successful
      UGRAA, 80% on the first attempt and 92% on the first or second attempt. The
      median time for access was 35 seconds, with an interquartile range of 31-55
      seconds. CONCLUSION: UGRAA improved first-attempt success rates and shortened the
      time needed for radial artery cannulation when compared to historical data of
      palpation-directed radial artery access. A large randomized trial of palpation
      versus UGRAA will be required to confirm this finding. Furthermore, this
      technique is easy to learn and incorporate into everyday practice in the cardiac
      catheterization lab.

PMID- 24296390
TI  - Concomitant transapical treatment of aortic stenosis and degenerated mitral
      bioprosthesis with two 29 mm Edwards Sapien XT prostheses.
AB  - An 85-year-old woman was admitted to our institution for effort dyspnea. She had
      a history of mitral valve replacement with a 29 mm Carpentier-Edwards
      bioprosthesis (Edwards Lifesciences). Transthoracic echocardiography (TTE) showed
      aortic stenosis and senescence of the mitral bioprosthesis. The heart team opted
      for a transapical transcatheter aortic valve implantation (TAVI) and mitral valve
      in-valve implantation (m-ViV). Two Edwards Sapien XT (ESXT) 29 mm devices were
      selected. To our knowledge, this is the first description of the concomitant
      transapical implantation of two 29 mm ESXTs for a combination of failed mitral
      bioprosthesis and native aortic stenosis.

PMID- 24296391
TI  - Ad hoc percutaneous left atrial appendage closure.
AB  - OBJECTIVES: To investigate the feasibility of ad hoc left atrial appendage (LAA)
      closure in patients in atrial fibrillation. BACKGROUND: Feasibility of ad hoc LAA
      closure depends, among other things, on transesophageal echocardiography (TEE)
      being omittable. METHODS: Patients underwent ad hoc LAA closure at the same
      sitting as coronary angiography. TEE guidance or sedation was omitted. Left
      atrial access was via coexisting patent foramen ovale (PFO) or a transseptal
      puncture. Arriving in the left atrium, a contrast medium injection was performed,
      avoiding LAA intubation to exclude thrombus in the LAA. Thereafter, the 13 Fr
      TorqVue delivery sheath (the largest one available and compatible with all
      occluders) was advanced into the LAA and the diameter of the landing zone was
      estimated using the outer diameter of the sheath as a reference. An accordingly
      selected Amplatzer Cardiac Plug was deployed in the LAA. RESULTS: Median CHA2DS2
      VASc score of the 13 included patients (8 males; age 76 years; interquartile
      range [IQR], 68-84 years) was 5 (IQR, 3-5) and HAS-BLED score was 3 (IQR, 2-4).
      Contrast medium injection to the left atrium did not reveal a thrombus in the LAA
      in any patient. The LAA closure procedures were uneventful and follow-up
      transthoracic echocardiography before discharge confirmed correct device
      position. Patients were discharged on acetylsalicylic acid and clopidogrel
      without vitamin-K antagonists. CONCLUSION: Ad hoc LAA closure using local
      anesthesia and fluoroscopy alone appears feasible.

PMID- 24296392
TI  - An unusual culprit: simple angioplasty for a complex disease.
AB  - We present the case of an atypical presentation of myelofibrosis presenting with
      acute inferior-wall ST-elevation myocardial infarction. Besides cigarette
      smoking, the patient had no known traditional cardiovascular risk factors like
      diabetes, hypertension, or a sedentary lifestyle. He, however, had a
      hypercoagulable state due to a myeloproliferative neoplasm. This demonstrates
      that the typical presentation of a common emergency condition may involve more
      complex underlying illness, which when identified, may change the approach to the
      management of the patient for a more optimal outcome.

PMID- 24296393
TI  - Anomalous muscle bundles causing double-chambered right ventricle in adults.
AB  - Double-chambered right ventricle (DCRV) causing right ventricular outflow tract
      (RVOT) obstruction, is an uncommon cardiac disease especially when first
      diagnosed in adults. Diagnosis can be challenging when it is asymptomatic. We
      report a 40-year-old man who was referred to cardiology for work-up of a heart
      murmur that was found on a routine physical examination prior to obtaining a
      pilot's license. A transesophageal echocardiogram (TEE) revealed a DCRV and a
      small perimembranous ventricular septal defect (VSD) with left-to-right shunt and
      severe RVOT obstruction. Right heart catheterization showed an estimated gradient
      of 135 mm Hg across the two chambers due to subpulmonary stenosis. The pressure
      in the proximal right ventricular chamber was 160/25 mm Hg and 25/17 mm Hg in the
      distal chamber. Surgical correction was successfully performed. A postoperative
      TEE showed no residual gradients across the RVOT. DCRV has been reported as a
      rare disease in adults. It is difficult to diagnose DCRV using the transthoracic
      echocardiogram in adults. However, subcostal windows can offer better
      visualization of subpulmonary outflow tract compared to the parasternal and
      apical windows. TEE remains the main non-invasive modality for diagnosing DCRV in
      adults. Cardiac magnetic resonance imaging and invasive testing can provide
      further information to confirm the diagnosis and guide therapeutic decisions.

PMID- 24296394
TI  - Mid-ventricular Tako-Tsubo cardiomyopathy with structurally normal coronary
      arteries confirmed by optical coherence tomography.
AB  - Tako-Tsubo cardiomyopathy is an entity of unknown etiology characterized by
      transient apical dyskinesia in patients with angiographically normal coronary
      arteries. However, atypical forms of Tako-Tsubo cardiomyopathy may also occur,
      affecting other myocardial segments. Optical coherence tomography has a unique
      resolution and may detect angiographically silent atherosclerotic coronary artery
      disease. In this report, we describe optical coherence tomography findings in a
      patient with atypical Tako-Tsubo cardiomyopathy presenting as transient mid
      ventricular ballooning.

PMID- 24296395
TI  - Stenting of central aortopulmonary shunt in a child with pulmonary atresia,
      ventricular septal defect, and severely hypoplastic pulmonary arteries.
AB  - A male infant was born at 28 weeks gestation weighing 850 g. He was diagnosed
      with pulmonary atresia, ventricular septal defect and major aorto-pulmonary
      collaterals with severely hypoplastic true pulmonary arteries. A 3.5 mm Gore-Tex
      central shunt was anastomosed from the ascending aorta to the main pulmonary
      artery at 4 months of age and a weight of 3.5 kg. The left pulmonary artery
      measured 1-2 mm and the right pulmonary artery measured 1 mm. His saturations
      increased from 70% to 85% following placement of the central shunt. At 16 months
      of age, his oxygen saturation decreased to 68%. Cardiac catheterization, using a
      retrograde approach, and angiography demonstrated a moderate degree of stenosis
      within the distal shunt and a severe left pulmonary arterial stenosis. A 4 x 18
      mm Multi-Link Vision coronary stent was implanted within the stenotic central
      shunt and angioplasty of the left pulmonary arterial stenosis was performed. The
      oxygen saturation improved to 84% after the procedure. Although stenting of the
      Blalock-Taussig shunt has been described previously, this represents one of the
      first reports of stenting of a central aortopulmonary shunt. This significantly
      improved the patient's oxygen saturation and allowed the potential for some
      further central pulmonary arterial growth prior to unifocalization procedure.

PMID- 24296396
TI  - Extracardial migration of an atrial septal defect occluder device.
AB  - Several complications have been reported regarding the percutaneous closure of
      secondary atrial septal defects such as erosion, thromboembolic events,
      arrhythmias, and endocarditis. In this report, we describe the case of a 75-year
      old woman who underwent percutaneous closure of a secondary atrial septal defect
      with a 12 mm Amplatzer septal occluder. Six months after the uneventful
      implantation of the device, we manifested an asymptomatic late embolization of
      the device in the abdominal aorta. The device was surgically retrieved.

PMID- 24296397
TI  - Vitrectomy for floaters: prospective efficacy analyses and retrospective safety
      profile.
AB  - PURPOSE: Floaters impact vision but the mechanism is unknown. We hypothesize that
      floaters reduce contrast sensitivity function, which can be normalized by
      vitrectomy, and that minimally invasive vitrectomy will have lower incidences of
      retinal tears (reported at 30%) and cataracts (50-76%). METHODS: Seventy-six eyes
      (34 phakic) with floaters were evaluated in 2 separate studies. Floater
      etiologies were primarily posterior vitreous detachment in 61 of 76 eyes (80%)
      and myopic vitreopathy in 24 of 76 eyes (32%). Minimally invasive 25G vitrectomy
      was performed without posterior vitreous detachment induction, leaving anterior
      vitreous, and using nonhollow probes for cannula extraction. Efficacy was studied
      prospectively (up to 9 months) in 16 floater cases with Freiburg Acuity Contrast
      Testing (Weber index [%W] reproducibility = 92.1%) and the National Eye Institute
      Visual Function Questionnaire. Safety was separately evaluated in 60 other cases
      followed up on an average of 17.5 months (range, 3-51 months). RESULTS: Floater
      eyes had 67% contrast sensitivity function attenuation (4.0 +/- 2.3 %W; control
      subjects = 2.4 +/- 0.9 %W, P < 0.013). After vitrectomy, contrast sensitivity
      function normalized in each case at 1 week (2.0 +/- 1.4 %W, P < 0.01) and
      remained normal at 1 month (2.0 +/- 1.0 %W, P < 0.003) and 3 months to 9 months
      (2.2 +/- 1.5 %W, P < 0.018). Visual Function Questionnaire was 28.3% lower in
      floater patients (73.2 +/- 15.6, N = 16) than in age-matched control subjects
      (93.9 +/- 8.0, N = 12, P < 0.001), and postoperatively improved by 29.2% (P <
      0.001). In the safety study of 60 floater cases treated with vitrectomy, none
      developed retinal breaks, infection, or glaucoma after a mean follow-up of 17.5
      months. Only 8 of 34 cases (23.5%) required cataract surgery (none younger than
      53 years) at an average of 15 months postvitrectomy. CONCLUSION: Floaters lower
      contrast sensitivity function, which normalizes after vitrectomy. Visual Function
      Questionnaire quantified improvement in satisfaction. Not inducing posterior
      vitreous detachment reduced retinal tear incidence from 30% to 0% (P < 0.007).
      Postvitrectomy cataract incidence was reduced from 50% to 23.5% (P < 0.02). This
      approach thus seems effective and safe in alleviating the visual dysfunction
      induced by floaters.

PMID- 24296398
TI  - Pigment epithelial tears associated with anti-VEGF therapy: incidence, long-term
      visual outcome, and relationship with pigment epithelial detachment in age
      related macular degeneration.
AB  - PURPOSE: To evaluate the prevalence of retinal pigment epithelium (RPE) tears
      associated with anti-VEGF therapy and its relation with retinal pigment
      epithelial detachment (PED). METHODS: A total of 226 patients with exudative age
      related macular degeneration treated with intravitreal anti-VEGF were included
      retrospectively in the study. The presence of RPE tears; the effect of the
      presence, height, and duration of PED on the rate of RPE tears; and change in
      visual acuity during follow-up were recorded. RESULTS: Among 226 study patients,
      28 (12.3%) had RPE tears. The RPE tear rate was significantly higher in patients
      with vascularized PED (vPED) than in those without PED (19.7% vs. 2.1%; P <
      0.001). The change in visual acuity after the formation of RPE tear was not
      statistically significant (on logMAR scale: 0.92 +/- 0.49 initially, 0.89 +/-
      0.41 after the RPE tear, 0.96 +/- 0.45 at the last follow-up; P = 0.613). Pigment
      epithelial detachment height >580 MUm (odds ratio = 69.4; 95% confidence interval
      = 16.7-288.1) and PED duration <= 4.5 months (odds ratio = 166.7; 95% confidence
      interval = 15.2-1000) were found to be significant risk factors for RPE tear
      formation. CONCLUSION: The RPE tears are not infrequent among eyes treated with
      intravitreal anti-VEGFs. The presence, increased height, and shorter duration of
      vPED are potential risk factors for RPE tears associated with anti-VEGF therapy.

PMID- 24296399
TI  - Estramustine-induced suicidal erythrocyte death.
AB  - BACKGROUND: The nitrogen mustard derivative of estradiol-17beta-phosphate
      estramustine is used for the treatment of prostate cancer. Estramustine may
      trigger suicidal death of cancer cells. Side effects of estramustine include
      anemia. At least in theory, estramustine could cause anemia by stimulation of
      eryptosis, the suicidal death of erythrocytes. Hallmarks of eryptosis include
      cell shrinkage, increased cytosolic Ca2+ activity ([Ca2+]), ceramide formation
      and phosphatidylserine translocation to the outer leaflet of the cell membrane
      with phosphatidylserine exposure at the erythrocyte surface. Eryptosis is
      stimulated by increase of cytosolic Ca2+ activity ([Ca2+]i). The present study
      explored whether estramustine triggers eryptosis. METHODS: [Ca2+]i was estimated
      from Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine
      exposure from annexin V binding, and hemolysis from hemoglobin release. RESULTS:
      A 24 h exposure to estramustine (<= 100 MUM) significantly increased [Ca2+]i,
      increased annexin V binding and increased hemoglobin release. The effect of
      estramustine on annexin V binding was significantly blunted by removal of
      extracellular Ca2+. CONCLUSIONS: Estramustine stimulates both, eryptosis and
      hemolysis. The estramustine induced translocation of phosphatidylserine to the
      cell surface is at least partially due to increase of cytosolic Ca2+ activity.

PMID- 24296400
TI  - Castrate-resistant prostate cancer with peritoneal metastases treated with
      docetaxel-based chemotherapy.
AB  - INTRODUCTION: To identify the risk factors, characteristics and prognosis of
      patients treated with docetaxel-based chemotherapy for peritoneal carcinomatosis
      due to metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We
      retrospectively reviewed our series of mCRPC patients with peritoneal metastases
      treated with docetaxel-based chemotherapy between 2004 and 2010. RESULTS: Six
      patients were identified from our institutions' internal cancer registry. Three
      out of these patients had been treated with laparoscopic radical prostatectomy
      (LRP). In addition to peritoneal metastases, other metastatic sites were mainly
      visceral. Only 1 patient developed bone metastases. Peritoneal carcinomatosis
      occurred mainly in patients with a high Gleason (= or >6) score since 5 out of
      our 6 patients had a Gleason score >=7. All 6 patients were treated with
      docetaxel-based chemotherapy when they developed castration resistance. Five
      patients benefitted from chemotherapy according to their PSA or RECIST responses.
      Median survival from the start of docetaxel was 24.5 months. CONCLUSIONS: Our
      retrospective analysis suggests that peritoneal carcinomatosis occurs mainly in
      patients with a high Gleason score. It is also possible that tumor seeding occurs
      during LRP. Patients with peritoneal carcinomatosis resistant to castration seem
      to benefit from docetaxel-based chemotherapy.

PMID- 24296401
TI  - Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro
      in vivo evaluations.
AB  - The present study deals with the development and evaluations of stomach-specific
      floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate
      based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and
      capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and
      potato starch weight masses on drug encapsulation efficiency (DEE) of beads and
      cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2)
      factorial design. The optimization results indicate increasing of DEE in the oil
      entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and
      potato starch weight masses. The optimized formulation showed DEE of 70.02 +/-
      3.16% and R10 h of 56.96 +/- 2.92%. These capsules showed floatation over 6h and
      sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study
      of optimized floating capsules in rabbits showed stomach-specific gastroretention
      over a prolonged period.

PMID- 24296402
TI  - Protection of growth in response to 28-homobrassinolide under the stress of
      cadmium and salinity in wheat.
AB  - This study examines the impact of 28-homobrassinolide (HBL) in alleviating the
      effects of cadmium (Cd) and salinity (NaCl) on wheat plants solely and against
      the synergy. The surface sterilized seeds of Triticum aestivum cv. PBW-373 were
      sown in the soil amended either with salinity or cadmium or both. The foliage in
      was sprayed at 20d after sowing (DAS) both in stressed and non-stressed plants.
      The spray of HBL at 20 DAS increased almost all the parameters while decreased
      the H2O2 content and lipid peroxidation in the leaves. The presence of cadmium
      and/or salinity decreased the values for all the growth and photosynthetic
      parameters but improved the activity of antioxidant enzymes and proline content
      in 30d old plants. However, the ill effects observed under NaCl and/or Cd
      treatment were completely overcomed by the spray of HBL to the plants at 20d
      stage. The spray of HBL to stressed plants further increased the antioxidant
      enzyme activities and proline content thereby giving tolerance to the plants
      against the stress. 

PMID- 24296403
TI  - Investigation of antihypertensive activity of carbopol valsartan transdermal gel
      containing 1,8-cineole.
AB  - The purpose of this work was to develop a transdermal gel formulation for
      enhanced delivery of valsartan for the management of hypertension. Transdermal
      gels bearing valsartan, carbopol and 1,8-cineole (penetration enhancer) were
      prepared and characterized for various parameters including in vitro skin
      permeation studies, pH, spreadability, viscosity, skin irritation potential and
      in vivo antihypertensive activity. Optimized valsartan gel formulation (VTGF9)
      showed highest transdermal flux (143.51 MUg/cm(2)/h), with an enhancement ratio
      of 4.53 when compared to control gel formulation (VTGF8). Incorporation of 1,8
      cineole and ethanol in gel formulation enhance the permeation of valsartan
      significantly. Skin irritation and histopathological study revealed that the
      VTGF9 was safe, less irritant and well tolerable formulation for transdermal
      delivery. In vivo antihypertensive activity revealed that optimized VTGF9 was
      successful in reverting the rat BP to normal values in experimental hypertensive
      rats. Finally, it could be concluded that VTGF9 accentuates the flux of valsartan
      and is an efficient transdermal therapeutic system for delivery of valsartan.

PMID- 24296404
TI  - Effects and mechanism of modified starches on the gel properties of myofibrillar
      protein from grass carp.
AB  - The effects and mechanism of cassava starch (CS), hydroxypropylated cassava
      starch (HCS) and cross-linked hydroxypropylated cassava starch (CHCS), on gel
      properties of myofibrillar protein (MP) from grass carp were investigated using
      texture analyzer, dynamic rheometer, scanning electron microscopy (SEM) and
      circular dichroism (CD). Water holding capacity (WHC) of MP gels increased from
      70% to ca. 90% with an increase in additive amount of modified starches (MS) and
      HCS improved WHC most effectively. The MS (HCS and CS) at proper additive amount
      (1.5 wt%) improved the textural properties of MP gels significantly (P<0.05). In
      rheological test, all MS-MP solutions showed viscoelastic nature of MP, but
      adding MS resulted in much higher G', suggesting the effect of MS (especially 2.5
      wt% CHCS) was considerable and equal to increasing protein concentration. The SEM
      photographs showed the MP gel with 2.5 wt% CHCS or 0.5 wt% HCS formed compact and
      homogeneous network, while the gel with CS agglomerated and the agglomerate
      phenomenon occurred more obviously with increasing additive amount. The addition
      of MS, especially CHCS, promoted the heat-induced conformational transition from
      the alpha-helix companied with beta-turn to beta-sheet, leading to the MP
      molecules stretching out.

PMID- 24296405
TI  - Anti-diabetic activity of cassava cross-linked octenyl succinic maltodextrin in
      STZ-induced diabetic mice.
AB  - The effect of cassava cross-linked octenyl succinic maltodextrin (CCOMD) on
      diabetic mice was investigated in this study. For CCOMD-L (low dose) and CCOMD-H
      (high dose) groups, the body weights were recovered by 14.9% and 18.5%,
      respectively, which were significantly higher than that of model control group.
      It was also found that the blood glucose and insulin levels were ameliorated in
      the diabetic mice by the CCOMD diet. Moreover, the CCOMD diet decreased the
      plasma total cholesterol level (8.1-9.1%) and LDL cholesterol level (28.9-39.4%),
      and improved the plasma HDL cholesterol level (13.8-15.3%) and intestine short
      chain fatty acid content. The results indicated that CCOMD administration may be
      helpful for treating and preventing hyperlipidemia and hyperglycemia in diabetes.

PMID- 24296406
TI  - Polysaccharides from Enteromorpha prolifera enhance the immunity of normal mice.
AB  - The effects of polysaccharides from Enteromorpha prolifera (PEP) on cell-mediated
      immunity, humoral immunity and mononuclear phagocytic system function were
      evaluated to assess the immunomodulatory potential of these macromolecules.
      Relevant immunological mechanisms were verified by biochemical assays and western
      blot analysis. Results showed that PEP could induce splenocyte proliferation. In
      vivo experiments on Kunming mice confirmed that PEP could improve cell-mediated
      immunity, humoral immunity and mononuclear phagocytic system function. To
      illustrate the mechanism, we determined several immune-related enzymes in the
      thymus and spleen. The results indicated that PEP could enhance the activities of
      alkaline phosphatase, superoxide dismutase and lactate dehydrogenase. PEP could
      also increase the level of NF-kappaB. These results suggested that PEP exhibited
      potent immunomodulatory properties and could be used as a novel potential
      immunostimulant in food and pharmaceutical industries. 

PMID- 24296407
TI  - Effects of epimedium polysaccharide-propolis flavone oral liquid on mucosal
      immunity in chickens.
AB  - A previous study found that epimedium polysaccharide (EP)-propolis flavonoid (PF)
      injection (EPI) produced reliable immunoenhancement. In this study, we
      investigate the effects of EP-PF oral liquid (EFO) on mucosal immunity in the
      chicken small intestine while using EPI, EP and PF as controls. Groups of
      fourteen-day-old chickens were given EFO orally at one of the three doses when
      they were vaccinated with ND vaccine. On days 7, 21 and 35 after the first
      vaccination, six chickens were selected randomly from each group for measurements
      of the sIgA and IL-17 contents of the washing liquors of the duodenum and
      jejunum, counts of the lymphocytes in the duodenal endothelium and counts of the
      IgA(+) cells in the jejunal endothelium and cecum tonsil. The results indicated
      that EFO significantly promoted the secretion of sIgA and IL-17 and increased the
      numbers of lymphocyte and IgA(+) cells. Furthermore, EFO was more efficient than
      EPI at the high and medium doses. These findings indicate that EPO may enhance
      intestinal mucosal immunity and may be exploited as an oral immunopotentiator. 

PMID- 24296408
TI  - Xylanase production from Bacillus aerophilus KGJ2 and its application in
      xylooligosaccharides preparation.
AB  - Xylanolytic enzyme was produced using a newly isolated Bacillus aerophilus KGJ2
      and low cost lignocellulosic sources in solid state fermentation. Seven different
      agricultural residues (wheat bran, tea dust, saw dust, paper waste, cassava
      bagasse, rice straw and rice husk) and six nitrogen source namely yeast extract,
      beef extract, peptone, ammonium nitrate, ammonium sulphate, and ammonium chloride
      were examined for xylanase production. Upon initial screening, wheat bran and
      ammonium chloride were chosen as suitable carbon source and nitrogen source
      respectively. Plackett-Burman fractional factorial design was employed to screen
      the important process variables affecting enzyme production. Substrate
      concentration, nitrogen source, moisture content and MgSO4.7H2O were identified
      as statistically significant variables. Subsequently Box-Behnken method was used
      to optimize the process conditions to achieve maximum xylanase yield. Under
      optimized conditions xylanase yield was 45.9 U/gds. Best xylanase activity was
      obtained at 70  degrees C and pH 4.0. It retained more than 90% activity after
      incubation at 80-90  degrees C for 60 min. The hydrolytic efficiency of xylanase
      on xylan was examined and xylobiose, xylotriose and xylotetrose were obtained as
      hydrolytic products.

PMID- 24296410
TI  - Bioactivity and biocompatibility of a chitosan-tobermorite composite membrane for
      guided tissue regeneration.
AB  - A polymer-mineral composite membrane of the mucopolysaccharide derivative,
      chitosan, and calcium silicate hydrate phase, tobermorite, was prepared by
      solvent casting and characterised by scanning electron microscopy (SEM) and
      Fourier Transform infrared spectroscopy (FTIR). The bioactivity and
      biocompatibility of the chitosan-tobermorite composite were evaluated in vitro
      with respect to its potential for use as a biodegradable guided tissue
      regeneration (GTR) membrane. The in vitro bioactivity of the composite was
      confirmed by the formation of crystalline substituted hydroxyapatite on the
      surface of the embedded tobermorite particles in simulated body fluid. The
      presence of the composite membrane was found to enhance the growth of MG63 human
      osteosarcoma cells by up to 30%. The findings of this initial study have
      indicated that this novel chitosan-tobermorite composite may be a suitable
      material for GTR applications. 

PMID- 24296409
TI  - Interaction of cholinesterase modulators with DNA and their cytotoxic activity.
AB  - This research was focused on a study of the binding properties of a series of
      cholinesterase reactivators compounds K075 (1), K027 (2) and inhibitors compounds
      K524, K009 and 7-MEOTA (3-5) with calf thymus DNA. The nature of the interactions
      between compounds 1-5 and DNA were studied using spectroscopic techniques (UV
      vis, fluorescence spectroscopy and circular dichroism). The binding constants for
      complexes of cholinesterase modulators with DNA were determined from UV-vis
      spectroscopic titrations (K=0.5 * 10(4)-8.9 * 10(5)M(-1)). The ability of the
      prepared analogues to relax topoisomerase I was studied with electrophoretic
      techniques and it was proved that ligands 4 and 5 inhibited this enzyme at a
      concentration of 30 MUM. The biological activity of the novel compounds was
      assessed through an examination of changes in cell cycle distribution,
      mitochondrial membrane potential and cellular viability. Inhibitors 3-5 exhibited
      a cytotoxic effect on HL-60 (human acute promyelocytic leukaemia) cell culture,
      demonstrated a tendency to affect mitochondrial physiology and viability, and
      also forced cells to accumulate in the G1/G0-phase of the cell cycle. The
      cholinesterase reactivators 1 and 2 were found relatively save from the point of
      view of DNA binding, whereas cholinesterase inhibitors 3-5 resulted as strong DNA
      binding agents that limit their plausible use.

PMID- 24296411
TI  - Effect of orally administered hydroxypropyl chitosan on the levels of iron,
      copper, zinc and calcium in mice.
AB  - Two hydroxypropyl chitosan HPCS samples (HPCS1 Mw 1.6 * 10(5), HPCS2 Mw 3.5 *
      10(4)) were prepared by the reaction of chitosan with propylene oxide under
      alkali conditions. The median lethal dose of the hydroxypropyl chitosan was
      greater than 10 g/kg for the laboratory mice. HPCS1 at the 0.1%, 1.0%, 1.5% and
      HPCS2 at the 1.0% level in diets were used to feed the mice for 90 days
      respectively. No pathological symptoms, clinical signs or deaths were observed
      for all mice. The weights of the mice in HPCS groups and control group had no
      significant difference. The levels of Fe, Cu, Zn and Ca in the mice were measured
      by atomic absorption spectrophotometry. HPCS had no significant effect on the
      levels of Fe, Cu, Zn and Ca in the tested mice's livers and hearts. However,
      hydroxypropyl chitosan at high dose exhibited inhibitory effects on the levels of
      Fe, Zn and Ca in some organizations.

PMID- 24296412
TI  - Immediate effectiveness of humming on the supraglottic compression in subjects
      with muscle tension dysphonia.
AB  - AIMS: To verify whether humming corrects supraglottic compression in muscle
      tension dysphonia (MTD) patients. METHODS: We enrolled 23 MTD participants (13
      male, 10 female) showing supraglottic compression. Each individual was instructed
      to perform 3 types of phonation under transnasal laryngofiberscopy: natural
      phonation, humming phonation without pitch change and subsequent um-hum
      phonation, i.e. humming with pitch glide up as if agreeing with someone. The
      degree of supraglottic compression was estimated with 2 parameters. The false
      vocal fold and anterior-posterior indices (the FVF and AP indices) were
      calculated by normalizing the lateral width and AP length of the visible vocal
      cords at phonation normalized to the mean vocal cord length at inspiration,
      respectively. These indices were compared among the tasks. RESULTS: All the MTD
      participants but 5 females accomplished decreases in the vocal roughness scores
      upon the phonatory tasks. The whole MTD group showed significant increases in the
      FVF and AP indices even after humming without pitch change with a dominance of
      the AP index. The humming-responsive MTD subgroup showed greater increases in
      both indices than the humming-resistant subgroup. CONCLUSION: These data
      demonstrate that humming corrects both the lateral and AP components of
      supraglottic compression in most MTD patients.

PMID- 24296413
TI  - [Endophthalmitis in patients with bullous keratopathy and therapeutic contact
      lenses wear].

PMID- 24296414
TI  - Do nutrients play a role in delirium?
AB  - PURPOSE OF REVIEW: This study will review the biologic roles of thiamine, niacin,
      folic acid, cobalamin, antioxidants, lipids, glucose, and water and their
      implications as contributors or causal agents in the development of delirium,
      particularly if deficiencies or excesses exist. RECENT FINDINGS: Knowledge on how
      overall nutritional status and individual nutrients predispose or directly lead
      to the development of delirium is currently very limited. Most studies in the
      area of nutrition and cognition still describe mental status changes using the
      term dementia and do not specifically address nutrition and delirium. However, as
      the brain pathophysiology that accompanies delirium has been furthered
      elucidated, it has become clear that nutritional imbalances can lead to these
      same physiologic changes in neuronal tissue. SUMMARY: Delirium, characterized by
      an acute change in mental status along with diminished awareness and attention
      and disturbances in memory, language, or perception, confers high rates of
      morbidity and mortality and can be difficult to both diagnose and treat. Although
      the cause of delirium is often multifactorial, nutritional status and nutrients
      may play a role in predisposing or directly causing this acute cognitive
      dysfunction. Many nutritional deficiencies or excesses (i.e., B vitamins,
      antioxidants, glucose, water, lipids) have been shown to alter the way one thinks
      and restoring the balance in many of these nutrients can lead to resolution of
      delirium.

PMID- 24296416
TI  - Life without the mitochondrial calcium uniporter.
AB  - Calcium enters mitochondria through a dedicated channel referred to as the
      mitochondrial calcium uniporter (MCU), whose molecular identity has long remained
      elusive. Since the discovery of the gene encoding the MCU protein two years ago,
      researchers have awaited the generation of a mouse lacking the MCU. These mice
      are fully viable and show defects limited to performance of high-energy-demanding
      exercises. Strikingly, no protection against necrosis is observed following
      ischaemia-reperfusion in the heart. 

PMID- 24296417
TI  - Centriole biogenesis in multiciliated cells.
AB  - Centrioles duplicate only once per cell cycle in proliferating cells, whereas in
      multiciliated cells, hundreds of centrioles form almost simultaneously. The
      molecular control mechanisms that govern centriole amplification in multiciliated
      cells are largely unknown. Two studies highlight Deup1 and CCDC78 as key players
      in this process. 

PMID- 24296415
TI  - The roles of evolutionarily conserved functional modules in cilia-related
      trafficking.
AB  - Cilia are present across most eukaryotic phyla and have diverse sensory and
      motility roles in animal physiology, cell signalling and development. Their
      biogenesis and maintenance depend on vesicular and intraciliary (intraflagellar)
      trafficking pathways that share conserved structural and functional modules. The
      functional units of the interconnected pathways, which include proteins involved
      in membrane coating as well as small GTPases and their accessory factors, were
      first experimentally associated with canonical vesicular trafficking. These
      components are, however, ancient, having been co-opted by the ancestral eukaryote
      to establish the ciliary organelle, and their study can inform us about ciliary
      biology in higher organisms. 

PMID- 24296418
TI  - Redox switch for actin.
AB  - Oxidation of actin methionine residues by the oxidation-reduction enzyme Mical is
      known to lead to actin filament depolymerization. SelR enzymes are now shown to
      reduce these oxidized actin methionines, revealing a regulated redox reaction
      mechanism through which cells control the assembly and disassembly of actin
      filaments. 

PMID- 24296419
TI  - Metabolomics and transcriptomics demonstrate severe oxidative stress in both
      localized chemotherapy-treated and bystander tumors.
AB  - BACKGROUND: Localized radiotherapy is long known to cause damages to not only
      targeted but also non-targeted cells, the so-called bystander (BS) effect.
      Recently, BS effect was demonstrated in response to chemotherapy. To get further
      insight into the mechanism of chemotherapy-induced BS effect in vivo, we
      investigated the response of normal tissues and untreated BS melanomas, at
      distance from localized chemotherapy-treated melanomas. METHODS: B16 melanoma
      cells were inoculated sc in one flank, in mice. Chemotherapy was administered
      intratumorally. After 3 weeks, untreated melanomas were implanted into the other
      flank. Tumors were analyzed morphologically, and using metabolomics and
      transcriptomics. RESULTS: Locally-treated melanomas showed growth inhibition and
      pleiotropic metabolic and transcriptional alterations. Tumors recovered slow
      proliferation while exhibiting prominent oxidative stress response (decreased
      glutathione level, and increased expression of genes including Mt1, Gpx3, Sod3,
      and Hmox1). Plasma contained increased levels of oxidative stress products.
      However, liver and soleus muscle displayed unaltered morphological
      characteristics. In contrast, untreated BS melanomas induced from naive B16 cells
      showed reduced growth, marked oxidative stress response (decreased glutathione
      level, and increased expression of genes including Sod2, Gpx1 and Gsr), and ras
      oncogene expression alterations. Furthermore, metabolomics and transcriptomics
      enabled to estimate the proportion of cells undergoing the BS effect within
      treated tumors. CONCLUSION: Treatment of tumors with chemotherapy induces BS
      effects, underpinned by oxidative stress, in abnormal proliferating tissues in
      vivo, not in normal tissue, that significantly contribute to overall tumor
      response. General significance BS effect significantly contributes to response to
      chemotherapy, and may be exploited to improve overall response to cancer
      treatment.

PMID- 24296420
TI  - MELD-Na: effective in predicting rebleeding in cirrhosis after cessation of
      esophageal variceal hemorrhage by endoscopic therapy.
AB  - BACKGROUND AND AIMS: There is no study verifying the predictive value of model
      for end-stage liver disease and sodium (MELD-Na) for rebleeding and its
      associated mortality in cirrhotic patients after cessation of acute esophageal
      variceal hemorrhage (AVH) by endoscopic therapy. This study aimed to determine
      the predictive value of MELD-Na by comparing with MELD or Child-Turcotte-Pugh
      (CTP) scores. PATIENTS AND METHODS: Consecutive adult cirrhotic patients after
      cessation of AVH by endoscopic therapy (endoscopic variceal ligation or
      sclerotherapy injections) within 48 hours of admission admitted from 2003 to 2012
      were analyzed. The clinical characteristics and laboratory data at admission were
      documented, based on which MELD-Na, MELD, and CTP scores were calculated.
      RESULTS: Among 429 patients who had complete control of AVH, 97 patients (22.6%)
      suffered esophageal variceal rebleeding within 3 months and 206 patients (48.0%)
      within 1 year. Fifty-three patients (12.4%) died within 3 months and 98 patients
      (22.8%) within 1 year from rebleeding. The area under receiver operator
      characteristics curve of the MELD-Na score for predicting rebleeding and its
      associated mortality was significantly higher than that of the MELD and the CTP
      score (rebleeding: 0.83 vs. 0.77 vs. 0.69 for 3 months and 0.85 vs. 0.80 vs. 0.65
      for 1 year, P<0.05; mortality: 0.81 vs. 0.75 vs. 0.66 for 3 months and 0.82 vs.
      0.78 vs. 0.68 for 1 year, P<0.05). CONCLUSIONS: The MELD-Na score is clinically
      useful in predicting 3-month and 1-year rebleeding and its associated mortality
      in cirrhotic patients after cessation of AVH by endoscopic therapy.

PMID- 24296421
TI  - Ciprofloxacin usage and bacterial resistance patterns in Crohn's disease patients
      with abscesses.
AB  - BACKGROUND: Ciprofloxacin is the antibiotic most frequently used in the treatment
      of Crohn's disease (CD). We attempted to identify the microorganisms present in
      CD-related intra-abdominal abscesses, their ciprofloxacin resistance patterns,
      and the clinical impact. METHODS: Microorganisms, their ciprofloxacin resistance,
      and clinical outcomes were retrospectively analyzed in 78 CD patients with intra
      abdominal abscesses, who underwent percutaneous drainage between March 1991, and
      November 2011. RESULTS: The median time from diagnosis of CD to abscess drainage
      was 59.5 months (range, 1 to 178 mo). As for bacteriology, the no-growth
      proportion was 38.5% (n=30), and 69 microorganisms belonging to 11 genera were
      isolated from the other 48 (61.5%) patients. Of the 69 microorganisms, 65 were
      bacteria, including 30 (43.4%) gram-positive, 28 (40.6%) gram-negative aerobes, 7
      (10.1%) gram-negative anaerobes, and 4 (4.1%) fungi. Streptococci spp. (25,
      36.2%) were the most common bacteria, followed by Escherichia coli (18, 26.1%).
      Nineteen of the 28 gram-negative aerobes (67.9%) were resistant to ciprofloxacin,
      including 14 of 18 (77.8%) E. coli isolates. When we compared clinical
      characteristics and treatment outcomes in 17 patients with ciprofloxacin
      resistant and 8 with ciprofloxacin-sensitive bacteria, we found that disease
      duration from diagnosis to drainage (97.2 vs. 50.7 mo, P=0.03) and median length
      of hospitalization (40 vs. 31 d, P=0.03) was significantly longer in the former.
      CONCLUSIONS: When gram-negative aerobes were isolated from abscesses in CD
      patients, more than two thirds were resistant to ciprofloxacin. Providers should
      consider this high rate of ciprofloxacin resistance when choosing first-line
      antibiotic treatment for CD-related intra-abdominal abscesses.

PMID- 24296422
TI  - Endoscopic management of biliary leaks after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has become the procedure of choice for management of
      symptomatic cholelithiasis. Although it has distinct advantages over open
      cholecystectomy, bile leak is more common. Endoscopic retrograde
      cholangiopancreatography is the diagnostic and therapeutic modality of choice for
      management of postcholecystectomy bile leaks and has a high success rate with the
      placement of plastic biliary stents. Repeat endoscopic retrograde
      cholangiopancreatography with placement of multiple plastic stents, a covered
      metal stent, or possibly cyanoacrylate therapy may be effective in refractory
      cases. This review will discuss the indications, efficacy, and complications of
      endoscopic therapy. 

PMID- 24296423
TI  - Lactobacillus reuteri strain combination in Helicobacter pylori infection: a
      randomized, double-blind, placebo-controlled study.
AB  - GOALS: The goals of this study were to investigate the role of a new probiotic
      preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in
      Helicobacter pylori infection. BACKGROUND: Specific probiotic strains play a role
      in H. pylori infection for their ability to decrease bacterial load and
      gastritis, prevent antibiotic-associated side effects, and increase the
      eradication rate. STUDY: This is a prospective, double-blind, randomized, placebo
      controlled study in a tertiary care setting. A total of 100 H. pylori-positive
      naive patients received either L. reuteri combination (2*10 Colony Forming Units)
      or placebo during a 3-phase study (pre-eradication, eradication, and follow-up).
      All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17),
      endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was
      confirmed by C-UBT 8 weeks after the completion of therapy. RESULTS: Fifty
      patients were allocated in each group. During pre-eradication period, C-UBT delta
      decreased by 13% in L. reuteri combination as compared with a 4% increase in
      placebo (-13.2+/-34% vs. 4.3+/-27%; P<0.03). During eradication, GSRS increased
      significantly in placebo as compared with L. reuteri combination (6.8+/-2.9 vs.
      4+/-3.1; P<0.01). Significantly less patients in L. reuteri combination as
      compared with placebo-reported side effects (40.9% vs. 62.8%; P<0.04). An
      abnormal G17 value was found in patients receiving placebo as compared with L.
      reuteri combination (28% vs. 12%; P<0.02). Eradication rate was 75% in L. reuteri
      combination and 65.9% in placebo (P=NS). L. reuteri combination increased
      eradication rate by 9.1% (odds ratio: 1.5). CONCLUSIONS: L. reuteri combination
      alone is able to exert an inhibitory effect on H. pylori growth, and when
      administered with eradication therapy, it determines a significant reduction in
      antibiotic-associated side effects. Moreover, L. reuteri combination was able to
      decrease serum G17 levels and to (not significantly) increase the H. pylori
      eradication rate.

PMID- 24296424
TI  - Recurrent small intestinal ileus secondary to valsartan treatment.

PMID- 24296425
TI  - Acceptance of split-dose bowel preparation regimen for colonoscopy by patients
      and providers.
AB  - BACKGROUND: Split-dose bowel preparation (split prep) for colonoscopy has been
      shown to be superior to conventional dosing (entire dose taken on the evening
      preceding colonoscopy) and has been endorsed by recent guidelines. A potential
      limitation is the requirement for patients to wake up early to drink the second
      half. METHODS: A group of colonoscopy patients, scheduled for morning procedures
      were surveyed regarding their opinion about a split prep regimen. The survey
      specifically asked if they would be willing to wake up at 4:00 AM to drink the
      second half of the preparation. Primary care providers (PCPs) were given a
      similar survey asking for their opinion about the willingness of their patients
      to take a split prep regimen. RESULTS: Among the 149 patients surveyed, 95
      patients (64%) were willing to wake up early to complete a split prep, whereas 54
      (36%) were not. The majority, 65 of 95 (68%) patients, preferred an early morning
      appointment. Only 3 of 95 (3%) patients preferred an afternoon one. There were no
      statistically significant differences between patients in favor of a split or
      conventional preparation, in respect to demographics, family history of
      colorectal cancer, or prior experience with colonoscopy. A total of 25 of 34 PCPs
      (74%) answered the survey. Only 14 PCPs (56%) thought their patients would be
      willing to wake up at 4:00 AM to complete the preparation. CONCLUSIONS: Despite a
      high level of apprehension among PCPs, the majority of colonoscopy patients seem
      willing to comply with a split prep. Therefore, split prep should be used
      whenever possible for colonoscopy.

PMID- 24296426
TI  - Should we measure fetal omphalocele diameter for prediction of perinatal outcome?
AB  - OBJECTIVE: To evaluate the fetal omphalocele diameter/abdominal circumference
      ratio (OD/AC) as a predictor of adverse perinatal outcome. METHODS: Analysis
      involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and
      absence of other major abnormalities. The OD/AC ratio was determined antenatally
      by ultrasound and the best cutoff for the prediction of neonatal death was
      determined by receiver operating characteristic curve analysis. Additional
      secondary outcomes included need for oral intubation in the first 24 h of life,
      two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and
      need for respiratory assistance >21 days, time to first oral feed, and time to
      hospital discharge. RESULTS: Fetal OD/AC did not change significantly with
      gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff
      for prediction was an OD/AC ratio >=0.26. In pregnancies with the first
      ultrasound evaluation performed before 31 weeks' gestation and an OD/AC >=0.26,
      the likelihood ratio for needing intubation in the first 24 h of life was 2.6
      (95% CI: 1.2-5.7), needing two-step surgery or use of mesh was 4.9 (95% CI: 1.9
      14.4), and postnatal death was 4 (95% CI: 1.9-7.5). CONCLUSION: A fetal
      ultrasound OD/AC ratio >=0.26 is associated with increased postnatal morbidity
      and mortality.

PMID- 24296427
TI  - Clinical characteristics and outcome of incidental atrial septal openings in very
      low birth weight infants.
AB  - BACKGROUND: Atrial septal openings (ASOs) are very common in premature infants.
      OBJECTIVE: The study aimed to evaluate the prevalence and natural course of ASOs
      in very low birth weight (VLBW) infants diagnosed in the first week of life and
      the association of ASOs with various clinical factors. METHODS: We
      retrospectively reviewed the medical records of 217 infants born with a weight of
      <1,500 g between January 2007 and December 2011. Echocardiography was conducted
      within the first week of life in all infants. Clinical factors were compared
      between infants with ASO and those with an intact atrial septum. ASO closure was
      confirmed by echocardiography at the 3-month follow-up and subsequently every 6
      months. RESULTS: The incidence of ASOs was 40.3% in VLBW infants. Patent ductus
      arteriosus (PDA) was associated with a higher incidence of ASO in a multivariate
      analysis (OR 4.005, 95% CI 2.015-7.960, p < 0.001), and PDA was a predictor of
      early ASO closure. The rate of oxygen requirement for at least 28 days was higher
      in infants with ASO, whereas oxygen dependency at 36 weeks' postmenstrual age did
      not differ between the infant groups. The mean time of closure was 5.8 +/- 7.1
      months of age (range 0-36). All followed infants showed spontaneous closure
      within 3 years. CONCLUSIONS: ASOs occur at a relatively high incidence in VLBW
      infants, but most of these close spontaneously within 3 years. PDA was predictive
      of ASO at the first echocardiography but did not delay ASO closure. The ASOs in
      VLBW infants were not a significant cause of concern.

PMID- 24296428
TI  - Cardiac fibroblasts recruit Th17 cells infiltration into myocardium by secreting
      CCL20 in CVB3-induced acute viral myocarditis.
AB  - AIMS: Th17 cells contributed to myocardial inflammatory injury in acute viral
      myocarditis (AVMC), and the migration of these cells were mainly mediated by
      CCL20-secreting inflammatory cells. However, whether and how the resident cells
      such as cardiomyocytes and cardiac fibroblasts could mediate Th17 cell migration
      into the heart remains unclear in AVMC. METHODS: The effect of CCL20 on the
      dynamic alterations of intracardiac Th17 cells and disease severity were
      investigated through the neutralization of CCL20 in AVMC mice. The key cells
      releasing CCL20 in the heart and the effects of CCL20-secreting cells on Th17
      cell arrest, migration and differentiation were detected in vitro. RESULTS:
      Neutralization of CCL20 efficiently repressed the myocardial inflammation along
      with the reduction of Th17 cell infiltrations in the course of AVMC. In vitro,
      after stimulations of TNF-alpha, IL-1beta and IL-17, cardiac fibroblasts rather
      than cardiomyocytes could be dominantly induced for CCL20 production. CCL20
      secreting cardiac fibroblasts boosted Th17 cell arrest on endothelium, and induce
      Th17 cell migration. However, CCL20 produced by cardiac fibroblasts had no effect
      on Th17 cell differentiation and IL-17 production. CONCLUSIONS: It firstly
      suggested that cardiac fibroblasts could recruit Th17 cells infiltration into
      myocardium by secreting CCL20 in AVMC.

PMID- 24296429
TI  - Facts about FCE (fludarabine, cytarabine, etoposide) in acute myeloid leukemia.

PMID- 24296430
TI  - Lysozyme, a mediator of sepsis that deposits in the systemic vasculature and
      kidney as a possible mechanism of acute organ dysfunction.
AB  - In septic shock (SS), dysfunction of many organ systems develops during the
      course of the illness, although the mechanisms are not clear. In earlier studies,
      we reported that lysozyme-c (Lzm-S), a protein that is released from leukocytes
      and macrophages, was a mediator of the myocardial depression and vasodilation
      that develop in a canine model of Pseudomonas aeruginosa SS. Whereas both of
      these effects of Lzm-S are dependent on its ability to intrinsically generate
      hydrogen peroxide, we subsequently showed that Lzm-S can also deposit within the
      vascular smooth muscle layer of the systemic arteries in this model. In the
      present study, we extend our previous findings. We used a canine carotid artery
      organ bath preparation to study the time course and dose dependence of Lzm-S
      deposition within the vascular smooth muscle layer. We used a human aortic
      vascular smooth muscle cell preparation to determine whether Lzm-S can
      persistently inhibit contraction in this preparation. We also used a canine P.
      aeruginosa model to determine whether Lzm-S deposition might occur in other
      organs such as the kidney, liver, and small intestine. The results showed that,
      in the carotid artery organ bath preparation, Lzm-S deposition occurred within
      minutes of instillation and there was a dose-response effect. In the human aortic
      vascular smooth muscle cell preparation, Lzm-S inhibited contraction during a 4
      day period. In the in vivo model, Lzm-S accumulated in the kidney and the
      superior mesenteric artery. In a canine renal epithelial preparation, we further
      showed that Lzm-S can be taken up by the renal tubules to activate inflammatory
      pathways. We conclude that Lzm-S can deposit in the systemic vasculature and
      kidneys in SS, where this deposition could lead to acute organ dysfunction. 

PMID- 24296431
TI  - Tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate:
      data to support prehospital use?
AB  - Trauma-induced coagulopathy (TIC) occurs early after severe injury. TIC is
      associated with a substantial increase in bleeding rate, transfusion
      requirements, and a 4-fold higher mortality. Rapid surgical control of blood loss
      and early aggressive hemostatic therapy are essential steps in improving
      survival. Since the publication of the CRASH-2 study, early administration of
      tranexamic acid is considered as an integral step in trauma resuscitation
      protocols of severely injured patients in many trauma centers. However, the
      advantage of en route administration of tranexamic acid is not proven in
      prospective studies. Fibrinogen depletes early after severe trauma; therefore, it
      seems to be reasonable to maintain plasma fibrinogen as early as possible. The
      effect of prehospital fibrinogen concentrate administration on outcome in major
      trauma patients is the subject of an ongoing prospective investigation. The use
      of prothrombin complex concentrate is potentially helpful in patients
      anticoagulated with vitamin K antagonists who experience substantial trauma or
      traumatic brain injury. Beyond emergency reversal of vitamin K antagonists,
      safety data on prothrombin complex concentrate use in trauma are lacking. 

PMID- 24296432
TI  - Challenges and possibilities in forward resuscitation.
AB  - The environmental and logistical constraints of the prehospital setting make it a
      challenging place for the treatment of trauma patients. This is perhaps more
      pronounced in the management of battlefield casualties before extraction to
      definitive care. In seeking solutions, interest has been renewed in implementing
      damage control resuscitation principles in the prehospital setting, a concept
      termed remote damage control resuscitation. These developments, while improving
      conflict survival rates, are not exclusive to the military environment, with
      similar situations existing in the civilian setting. By understanding the
      pathophysiology of shock, particularly the need for oxygen debt repayment,
      improvements in the assessment and management of trauma patients can be made.
      Technology gaps have previously hampered our ability to accurately monitor the
      prehospital trauma patient in real time. However, this is changing, with devices
      such as tissue hemoglobin oxygen saturation monitors and point-of-care lactate
      analysis currently being refined. Other monitoring modalities including newer
      signal analysis and artificial intelligence techniques are also in development.
      Advances in hemostatic resuscitation are being made as our understanding and
      ability to effectively monitor patients improve. The reevaluation of whole-blood
      use in the prehospital environment is yielding favorable results and challenging
      the negative dogma currently associated with its use. Management of trauma
      related airway and respiratory compromise is evolving, with scope to improve on
      currently accepted practices. The purpose of this review is to highlight the
      challenges of treating patients in the prehospital setting and suggest potential
      solutions. In doing so, we hope to maintain the enthusiasm from people in the
      field and highlight areas for prehospital specific research and development, so
      that improved rates of casualty survival will continue. 

PMID- 24296433
TI  - Codonopsis pilosula polysaccharide attenuates cecal ligation and puncture sepsis
      via circuiting regulatory T cells in mice.
AB  - BACKGROUND: Codonopsis pilosula polysaccharide (CPPS) isolated from one of the
      Chinese herbs is known to have a variety of immunomodulatory activities. However,
      it is not clear whether CPPS can exert an effect on the immune functions of
      regulatory T cells (Tregs). This study was carried out to investigate the effect
      of CPPS on the immune function of peripheral blood Tregs in sepsis induced by
      cecal ligation and puncture (CLP). METHODOLOGY AND PRINCIPAL FINDINGS: BALB/c
      mice were randomly divided into five groups: sham group, CLP group, CLP with CPPS
      (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3,
      and 4 after CLP, respectively, with eight animals at each time point. Magnetic
      microbeads were used to isolate peripheral blood Tregs and CD4 T cells.
      Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed
      by flow cytometry, and coculture medium cytokines levels were determined with
      enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3
      in the Treg from CLP group were markedly increased in comparison to the sham
      group. Administration of CPPS could significantly decrease the TLR4 level and
      inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time,
      proliferative activity and expression of interleukin 2 and interleukin 2Ralpha on
      CD4 T cells were restored. In contrast, anti-TLR4 antibody could block the effect
      of CPPS on Treg immune function. CONCLUSIONS: Codonopsis pilosula polysaccharide
      might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and
      trigger a shift of TH2 to TH1 with activation of CD4 T cells in sepsis induced by
      CLP.

PMID- 24296434
TI  - Role of transfused red blood cells for shock and coagulopathy within remote
      damage control resuscitation.
AB  - The philosophy of damage control resuscitation (DCR) and remote damage control
      resuscitation (RDCR) can be summarized by stating that the goal is to prevent
      death from hemorrhagic shock by "staying out of trouble instead of getting out of
      trouble." In other words, it is preferred to arrest the progression of shock,
      rather than also having to reverse this condition after significant tissue damage
      and organ injury cascades are established. Moreover, to prevent death from
      exsanguination, a balanced approach to the treatment of both shock and
      coagulopathy is required. This was military doctrine during World War II, but
      seemed to be forgotten during the last half of the 20th century. Damage control
      resuscitation and RDCR have revitalized the approach, but there is still more to
      learn about the most effective and safe resuscitative strategies to
      simultaneously treat shock and hemorrhage. Current data suggest that our
      preconceived notions regarding the efficacy of standard issue red blood cells
      (RBCs) during the hours after transfusion may be false. Standard issue RBCs may
      not increase oxygen delivery and may in fact decrease it by disturbing control of
      regional blood flow distribution (impaired nitric oxide processing) and failing
      to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity).
      Standard issue RBCs may assist with hemostasis but appear to have competing
      effects on thrombin generation and platelet function. If standard issue or RBCs
      of increased storage age are not optimal, then are there alternatives that will
      allow for an efficacious and safe treatment of shock while also supporting
      hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10
      days provide an outcome advantage. A resurgence in the study of whole blood
      stored at 4 degrees C for up to 10 days also holds promise. Two randomized
      controlled trials in humans have indicated that following transfusion with either
      whole blood stored at 4 degrees C or platelets stored at 4 degrees C there was
      less clinical bleeding than when blood was reconstituted with components or when
      platelets were stored at 22 degrees C. Early reversal of shock is essential to
      prevent exacerbation of coagulopathy and progression of cell death cascades in
      patients with severe traumatic injuries. Red blood cell storage solutions have
      evolved to accommodate the needs of non-critically ill patients yet may not be
      optimal for patients in hemorrhagic shock. Continued focus on the recognition and
      treatment of shock is essential for continued improvement in outcomes for
      patients who require damage control resuscitation and RDCR. 

PMID- 24296435
TI  - A novel C1q-domain-containing (C1qDC) protein from Mytilus coruscus with the
      transcriptional analysis against marine pathogens and heavy metals.
AB  - The C1q-domain-containing (C1qDC) proteins, which are involved in various
      processes of vertebrates, are important pattern recognition receptors in innate
      immunity of invertebrates. In present study, a novel C1qDC was identified from
      Mytilus coruscus (designated as McC1qDC), which was 917 bp in length encoding 236
      amino acids with a typical signal peptide of 19 amino acid residues in N
      terminus. Based on its conserved C1q domain and molecular architecture of 10 beta
      strand jelly-roll folding topology structure, McC1qDC might be classified as a
      member of the C1q family. The mRNA transcript of McC1qDC was predominantly
      detectable in the hemocytes, and a less degree in gill, gonad and mantle, but
      trace in foot, adductor and digestive gland. Upon induction by Vibrio harveyi and
      Vibrio alginolyticus, McC1qDC expression was significantly up-regulated. Time
      dependent mRNA expression of McC1qDC was found during copper and cadmium exposure
      for its heavy metal-binding domain. These results indicated that McC1qDC was a
      novel member of the C1qDC protein family as a pattern recognition receptor
      against pathogens, and might be developed as a potential indicator for monitoring
      heavy metals pollution.

PMID- 24296436
TI  - Morphologic, cytometric and functional characterization of the common octopus
      (Octopus vulgaris) hemocytes.
AB  - The hemocytes of Octopus vulgaris were morphologically and functionally
      characterized. Light and electron microscopy (TEM and SEM), and flow cytometry
      analyses revealed the existence of two hemocyte populations. Large granulocytes
      showed U-shaped nucleus, a mean of 11.6 MUm+/-1.2 in diameter with basophilic
      granules, polysaccharide and lysosomic deposits in the cytoplasm. Small
      granulocytes measured a mean of 8.1 MUm+/-0.7 in diameter, and have a round
      nucleus occupying almost the entire cell and few or not granules in the
      cytoplasm. Flow cytometry analysis showed that large granulocytes are the
      principal cells that develop phagocytosis of latex beads (rising up to 56%) and
      ROS after zymosan stimulation. Zymosan induced the highest production of both ROS
      and NO. This study is the first tread towards understanding the O. vulgaris
      immune system by applying new tools to provide a most comprehensive morpho
      functional study of their hemocytes.

PMID- 24296437
TI  - Influence of continuous light treatment on expression of stress biomarkers in
      Atlantic cod.
AB  - Continuous light treatment during early juvenile stages in Gadus morhua is a
      common farming management practice but the effects of these unnatural light
      conditions on fish stress have received scant attention. In the present study we
      investigated how continuous illumination affects transcription levels of key
      stress-related and antimicrobial peptide genes in juvenile Atlantic cod. Gene
      expression quantification by real-time PCR revealed higher levels of transcripts
      coding for antioxidant enzymes, namely superoxide dismutase, catalase and
      glutathione reductase in liver of fish reared under continuous illumination,
      concomitantly with a 43% decrease in glutathione content. Transcription of
      antimicrobial peptides such as piscidins, hepcidin and cathelicidin was also
      affected by constant illumination. Overall, the significant changes in liver
      transcript levels of these biomarkers in response to continuous light may be an
      adaptation to light stress. 

PMID- 24296438
TI  - Identification and characterization of Cynoglossus semilaevis microRNA response
      to Vibrio anguillarum infection through high-throughput sequencing.
AB  - MicroRNAs (miRNA) play key regulatory roles in diverse biological processes.
      Cynoglossus semilaevis is an important commercial mariculture fish species in
      China. To identify miRNAs and investigate immune-related miRNAs of C. semilaevis,
      we performed high-throughput sequencing on three small RNA libraries prepared
      from C. semilaevis immune tissues (liver, head kidney, spleen, and intestine).
      One library was prepared under normal conditions (control, CG); two were prepared
      during Vibrio anguillarum infection, where vibriosis symptoms were obvious and
      non-obvious (HOSG and NOSG, respectively). We obtained 11,216,875, 12,313,404,
      and 11,398,695 clean reads per library, respectively. Bioinformatic analysis
      identified 452 miRNAs, including 24 putative novel miRNAs. We analyzed
      differentially expressed miRNAs between two libraries using pairwise comparison.
      For NOSG-CG, there was significant differential expression of 175 (38.72%)
      miRNAs. There was significant differential expression of 215 (47.57%) miRNAs
      between HOSG and CG. Compared with CG, The HOSG-NOSG comparison revealed
      significantly different expression of 122 (26.99%) miRNAs respectively. Real-time
      quantitative PCR (RT-qPCR) experiments were performed for 10 miRNAs of the three
      samples, and agreement was found between the sequencing and RT-qPCR data. For
      miRNAs that were significantly differentially expressed, functional annotation of
      target genes by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and
      Genomes pathway analysis indicated that a set of miRNAs that were expressed
      highly abundantly and significantly differentially were might involved in immune
      system development and immune response. To our understanding, this is the first
      report of comprehensive identification of C. semilaevis miRNAs being
      differentially regulated in immune tissues (liver, head kidney, spleen, and
      intestine) in normal conditions relating to V. anguillarum infection. Many miRNAs
      were differentially regulated upon pathogen exposure. This work provides an
      opportunity for further understanding of the molecular mechanisms of miRNA
      regulation in C. semilaevis host-pathogen interactions. 

PMID- 24296439
TI  - Whole blood transcriptome comparison of pigs with extreme production of in vivo
      dsRNA-induced serum IFN-a.
AB  - Interferon (IFN) is one of the major regulators of innate immunity, it also
      mediates the adaptive immune responses to a broad spectrum of pathogens. This
      study aims in identifying differences between high vs. low INF-a responders which
      were chosen based on serum INF-a levels at 4 h post poly I:C treatment. A
      transcriptomic analysis was designed to describe the whole blood differential
      transcriptomal response to poly I:C by pigs with high vs. low IFN alpha levels.
      The capability of producing dsRNA (poly I:C)-induced serum IFN-a is highly
      variable in pig population. The high INF-a responders had 328 unique
      differentially expressed genes, suggesting that the HIGH pigs have greater
      responsiveness upon the dsRNA simulation. Based on the results, the interferon
      dependent antiviral responsiveness through the IFN-stimulated genes (ISGs) is
      likely more effective in HIGH pigs. Inferring from the known organization of IFN
      pathways, the reason for the more IFN-a production in the HIGH pigs was likely
      due to the enhanced expression of IRF-7 in TLR or RIG- I/MDA5 signaling pathways.
      Furthermore, the larger number of the altered genes in the HIGH pigs after
      simulation is also possibly because of the greater number of the altered
      transcription factors. To our knowledge, this is the first report of comparative
      transcriptomic analysis to advance our understanding of whole blood immune
      response in pigs with different in vivo poly I:C-inducted IFN-a levels. The paper
      significantly expands our knowledge of how pigs respond to poly I:C which is
      highly relevant for understanding resistance to viral infections and also for
      vaccine development.

PMID- 24296440
TI  - Thioredoxin peroxidase gene is involved in resistance to biocontrol fungus
      Nomuraea rileyi in Spodoptera litura: gene cloning, expression, localization and
      function.
AB  - Thioredoxin peroxidases (Tpxs) are a ubiquitous family of antioxidant enzymes
      that play important roles in protecting organisms against oxidative stress. Here,
      one Tpx was cloned from Spodoptera litura named as SlTpx. The full-length cDNA
      consists of 1165 bp with 588 bp open reading frame, encoding 195 amino acids. The
      putative amino acid sequence shared >70% identity with Tpxs from other insects.
      Phylogenetic analysis revealed that SlTpx is closely related to other available
      lepidopteran Tpxs. Real-time PCR analysis showed that SlTpx can be induced by
      Nomuraea rileyi infection in some detected tissues at the mRNA level. The
      strongest expression was found in hemocytes of unchallenged and N. rileyi
      challenged S. litura. Western blotting showed SlTpx protein in the hemocytes,
      head and cuticle from normal S. litura. However, when N. rileyi was inoculated
      into the body cavity of S. litura larvae, SlTpx protein was detected in head,
      hemocytes, fatbody, midgut, malpighian tubule, but not in the hemolymph and
      cuticle. Moreover, time-course analysis showed that SlTpx mRNA/protein expression
      levels were up-regulated in the hemocytes, when S. litura were infected by N.
      rileyi or injected with H2O2. The levels of N. rileyi-induced reactive oxygen
      species (ROS) in hemocytes were evaluated, and revealed that N. rileyi infection
      caused generation of ROS, and induced changes in expression of SlTpx. In
      addition, the heterologously expressed protein of this gene in Escherichia coli
      showed antioxidant activity; it removed H2O2 and protected DNA. Knocking down
      SlTpx transcripts by dsRNA interference resulted in accelerated insect death with
      N. rileyi infection. This is believed to be the first report showing that SlTpx
      has a significant role in resisting oxidative stress caused by N. rileyi
      infection.

PMID- 24296441
TI  - Gene therapy.

PMID- 24296442
TI  - Induced pluripotent stem cells (iPSc) for gene therapy.
AB  - The generation of autologous pluripotent stem cells by reprogramming and then
      their differentiation into any cell type is a very attractive prospect for
      biomedicine. Additionally, if it were possible to repair malfunctioning genes it
      would mean that there is hope for patients suffering from incurable diseases in
      which conventional treatment does not give satisfactory results. Data from animal
      models are promising. But there are still issues that must be solved, such as the
      low efficiency of the derivation of induced pluripotent cells, and most
      importantly, making sure that the techniques used both for reprogramming cells,
      as well as for gene therapy are safe. 

PMID- 24296443
TI  - siRNA preparations in gene therapy of melanoma.
AB  - Melanoma is a type of malignant skin cancer, characterized by a steadily
      increasing rate of morbidity, making it a continuous challenge for modern
      oncology. In recent years there has been a significant increase in developing
      gene therapy approaches for the treatment of cancer. The phenomenon of RNA
      interference initiated studies on the inhibition of the expression of selected
      genes by small interfering RNA (siRNA) in cells. The use of siRNA preparations
      for the treatment of patients depends on the transfection efficiency and the
      level of silencing the targeted genes. Currently, preclinical and clinical
      studies are being conducted in order to test the effectiveness and safety of
      siRNA preparations. 

PMID- 24296444
TI  - Vectrology of adeno-associated viruses (AAV).
AB  - In vivo gene replacement is one of the most compelling concepts in modern
      medicine. Adeno-associated virus (AAV) vectors are currently among the most
      frequently used viral vectors for gene therapy and they have shown therapeutic
      efficacy in a range of animal models. The lack of pathogenicity of the virus, low
      immunogenicity, its stability, and many available serotypes have increased AAV's
      potential as a delivery vehicle for gene therapy applications. There are some
      limitations to the use of rAAV in gene therapy. The first is their size. Due to
      the small size of the vector, the ability to conduct a therapeutic gene
      expression cassette is limited. Another limitation is the common occurrence of
      neutralizing antibodies in human populations. This review will focus on the
      biology of AAV, its use as a vector for gene therapy and mechanisms of AAV/host
      cell interaction. 

PMID- 24296445
TI  - [Genetic bases of autism spectrum disorders].
AB  - Autism spectrum disorders (ASDs) are an etiologically and clinically
      heterogeneous group of neurodevelopmental disorders affecting approximately 0.6
      1% of the general population. ASDs are characterized by deficits in social
      communication, impaired language development, and stereotyped repetitive
      behaviour. The impact of genetic factors in ASDs has been confirmed in the past
      few years. Numerous studies have shown that among patients with ASDs,
      approximately 10% have DNA copy number variation and 10-20% point mutations. Most
      of the deficiencies identified in individuals with ASDs relate to genes encoding
      proteins involved mainly in the development of neurons and their synapses
      functioning in various signaling pathways. Due to the large heterogeneity of
      identified changes in the genome of individuals with ASDs, the newest techniques
      enabling analysis of the entire genome in one study (microarrays, next-generation
      sequencing) are the methods of choice in the diagnostics of this pathology.

PMID- 24296446
TI  - [Epidemiology of infections in very low birth weight infants. Polish Neonatology
      Network research].
AB  - AIM OF STUDY: 1. prospective record of infections; 2. prevention of nosocomial
      infections by providing current data about infections, which are significant for
      making therapeutic decisions. MATERIAL AND METHODS: Recorded infections: early
      onset sepsis (congenital), late-onset sepsis (acquired in hospital), necrotising
      enterocolitis (NEC), pneumonia. Infections were diagnosed and qualified on the
      basis of definitions of infections based on the National Nosocomial Infections
      Surveillance (NNIS) criteria, developed by CDC, USA, including modifications of
      German Neo-KISS programme. Infection control was realised as a part of common
      research project of "Polish Neonatology Network", appointed by the decision of
      the Minister of Science and Higher Education no. 669/E-215/BWSN- 0180/2008 dated
      20.05.2008 r. The study was conducted by 6 Polish neonatology units, Microbiology
      Chair of Jagiellonian University Collegium Medicum and Institute of Theoretical
      and Applied Computer Science. Infants with birth weight lower than 1500 g were
      qualified for the study. RESULTS: Between 1.01.2009 and 31.12.2009, 910 patients
      were registered, i.e. 19.1% of VLBW infants born in that period. The conducted
      analysis showed significant differences between centres in gestational age, birth
      weight, hospitalisation, use of invasive procedures, antibiotics and parenteral
      feeding. Cumulative morbidity rate was 68.5% total. Blood infection (sepsis) was
      the most commonly observed type of infection: 268 cases - 43.1% of all recorded
      forms of infection. Pneumonia was diagnosed in 242 cases, 38.8% total. NEC
      constituted 12.7% studied infections (79 cases). Apart from NEC, the risk of
      other forms of infection differed between centres. Dominant etiologic factor of
      all infections were Gram-positive cocci, which constituted 565 isolated
      microorganisms. Among them coagulase-negative staphylococci (CNS) were the most
      common (41.7%), while Staphylococcus aureus was fourth most frequent etiologic
      factor of infections (6.3% total). CONCLUSIONS: 1. Introduction of unified
      definition and criteria for diagnosing infections and the use of morbidity rates
      enables comparative analysis of epidemiology of infections in neonatal intensive
      care units. 2. Due to significant differences observed between prophylactic and
      therapeutic procedures in various units, it is essential to propose Polish
      recommendations regarding control over etiology of infections and use of invasive
      procedures, such as intravenous catheters and ventilation. 3. It is essential to
      undertake action leading to fully rational antibiotic therapy, because overuse of
      antibiotics leads to bacterial resistance and increases incidence of infections.

PMID- 24296447
TI  - The concentrations of bile acids and erythropoietin in pregnant women with
      intrahepatic cholestasis and the state of the fetus and newborn.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is not a common complication of
      pregnancy, but may be a threat to fetal condition. The elevated level of bile
      acids defines ICP and determines its severity. Indicators of hepatocyte damage
      during ICP are elevated ALT and AST. The fetal condition in the ICP depends on
      the degree of liver damage. The most common complication is preterm delivery, but
      the risk of fetal death is currently around 3.5%. Erythropoietin is a peptide
      hormone produced mostly in the kidneys and liver due to tissue hypoxia. EPO
      concentration in the blood serum of pregnant women increases, because of its
      production in the placenta. Reducing the blood flow through the fetal-placental
      unit is the cause of fetal complications associated with ICP. The reason for
      blood flow the decrease is elevated TBA concentration. The hypothesis of the
      study assumed that in the course of ICP, elevated bile acids reduce blood flow
      through the fetal-placental unit, which causes placental hypoxia, and which can
      lead to the increased secretion of EPO in the placenta. THE AIM: of this study
      was to find a correlation between high levels of bile acids and concentration of
      erythropoietin in the serum of women with ICP without anemia and renal
      dysfunction and to evaluate the course and outcome of pregnancy in women with
      ICP. MATERIAL AND METHODS: 73 pregnant women from the Department of Obstetrics
      and Gynaecology, Institute of Mother and Child in Warsaw, were included in the
      study. 33 pregnant women with ICP were included in group I. Group II (control)
      consisted of 40 women with pregnancy without ICP. The inclusion criteria for the
      study in group I were as follows: TBA>=11 MUmol/l; elevated liver enzymes: ALT>41
      U/l and/ or AST>40 U/l; and the presence of pruritus (current or history). The
      exclusion criteria included: anemia (HGB<11 g/dl); viral hepatitis A, B, C; other
      abnormalities of the liver and of the biliary tract; alcohol and drug addiction;
      HIV infection; diseases of skin with itching and rash; acute and chronic kidney
      disease; bone disease; acute and chronic bleeding in pregnancy and preeclampsia.
      Laboratory analysis of the parameters of liver function, kidney function and
      blood counts was performed on the same day as the TBA and EPO concentration. The
      intensity of pruritus in patients with ICP was determined on the basis of a
      special 5-degree scale, proposed by the author. the conditions of fetuses were
      monitored during laboratory tests of the pregnant women and delivery with
      cardiotocography and ultrasound. Analysis of the newborns was based on the
      following data: gestational age at delivery, birth weight, 1-minute and 5-minute
      Apgar scores, blood gas parameters in the umbilical artery. The statistical
      analysis of clinical and laboratory parameters was performed using Statistica 5.5
      PL package. The results were analyzed in order to find significant differences
      between them. RESULTS: In the group of pregnant women with ICP mean gestational
      age at delivery was 35.97+/-1.86 weeks, in the control group 38.1+/-1.46 weeks
      (p<0.05). The percentage of preterm births (<37 weeks) in group I was 45.5%, in
      group II 15% (p<0.05). At the time of delivery in group I fetal hypoxia symptoms
      were observed in 9.8% of fetuses vs 17.4% in group II (p=ns.). In the group of
      women with ICP 36.6% of newborns had low birth weight (less than 2500 g),
      including 2.4% of extremely low birth weight (<1000 g). In group II, the
      percentage of infants with low birth weight was 10.9% (p<0.05). The average 1
      minute and 5-minute Apgar scores were lower in group I compared to group II
      (p<0.05). The average TBA concentration was 22.82+/-14.78 MUmol/L in group I vs
      2.43+/-2.04 MUmol/L in group II (p<0.05). The obtained data show that the
      intensity of pruritus was not directly related to the concentration of bile
      acids. The activity of liver enzymes in the group of women with ICP was
      significantly increased compared to controls. There were no cases of jaundice
      among the women examined. Among coagulation parameters in group I, significantly
      elevated concentration of fibrinogen (p<0,05) was found. Differences in the
      values of selected markers of renal function (urea, creatinine) and hematological
      parameters were not statistically significant. Erythropoietin concentrations in
      both groups were similar. In group I the mean value was 17.35+/-8.86 mU/ml and in
      the control group 18.12+/-9.48 mU/ml (p>0.05). CONCLUSIONS: In the group of
      pregnant women with ICP there was no correlation between the concentration of
      bile acids and erythropoietin. Preterm delivery and worse neonatal outcome were
      more common in the ICP group, which indicates that perinatal care should be
      improved and further studies are needed.

PMID- 24296448
TI  - Serum concentrations of sclerostin and bone turnover markers in children with
      cow's milk allergy.
AB  - THE AIM: of this study was to assess concentrations of sclerostin and biochemical
      markers of bone metabolism in children with cow's milk allergy. MATERIAL AND
      METHODS: The study included 45 children (age range 2-6 years) with diagnosed
      cow's milk allergy, who were on a dairy-free diet and under systematic medical
      and dietary control at the Institute of Mother and Child in Warsaw. The control
      group consisted of 40 healthy children (2-6 years), who did not have any symptoms
      of cow's milk allergy nor any diseases influencing bone metabolism. Their diets
      included milk and dairy products. Dietary intake of macro- and micronutrients was
      assessed based on 3-day records using the Dietetyk2(r) nutritional program. In
      the serum samples, we measured concentrations of calcium, phosphate and total
      alkaline phosphatase by standard methods, 25-hydroxyvitamin D3 by
      chemiluminescence method and bone metabolism markers by immunoenzymatic methods.
      The Statistica (version 10.0) computer software was used for statistical
      analysis. RESULTS: The nutritional status of studied children based on BMI value
      was normal. In all patients, the average daily value of dietary energy and
      percentage of energy from protein, fat and carbohydrates were consistent with the
      recommended values. The intake of calcium in the diets of all children was
      deficient, however, the intake of vitamin D was consistent with recommendations
      in the children with allergy, while in the healthy children it was below the
      recommended values. Mean serum concentrations of calcium, phosphate, alkaline
      phosphatase, 25-hydroxyvitamin D3, osteocalcin and C-terminal telopeptide of type
      I collagen were similar in both studied groups. We observed significantly lower
      sclerostin levels in children with cow's milk allergy (0.295+/-0.116 ng/ml) than
      in the healthy children (0.353+/-0.126 ng/ml) (p<0.05). The ratio of cytokines
      RANKL/OPG (receptor activator of nuclear factor kappaB ligand/osteoprotegerin)
      was significantly higher in children with allergy compared with their healthy
      counterparts (p<0.05). CONCLUSIONS: Basic laboratory parameters related to bone
      turnover in children with cow's milk allergy, who were under medical and
      nutritional care, were normal. Reduced levels of sclerostin and increased ratio
      of cytokines RANKL/OPG may suggest disturbances in the balance between bone
      formation and bone resorption in these patients. Further research is needed on
      bone metabolism in children with food allergy, who due to the use an elimination
      diet may be at risk of developing abnormalities in the skeletal system.

PMID- 24296449
TI  - Smith-Lemli-Opitz syndrome - clinical consequences for dental care.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is a congenital, genetically conditioned,
      metabolic disorder with autosomal recessive inheritance. The syndrome is caused
      by high levels of cholesterol precursors, i.e. 7-dyhdrocholesterol (DHCR7) and 8
      dehydrocholesterol (DHCR8), which results in cholesterol synthesis disorders.
      Cholesterol deficiency leads to a series of developmental disorders in the foetus
      and in extreme cases even death. The diagnosis of that congenital metabolic
      disorder is difficult due to a diversity of clinical symptoms (there are many
      mutations of the DHCR7 and DHCR8 genes), which can be exemplified by such cases
      as that of the 5-year-old boy with SLOS described below. In the presentation the
      authors have emphasized the problems related to hygienic procedures of the oral
      cavity and dental treatment, as well as the importance of the early diagnosis of
      the syndrome and of cooperation with parents. The publication aims at drawing the
      attention of clinicians to the need of taking SLOS into account in the
      differential diagnostics in children. 

PMID- 24296450
TI  - [Incidence of dental caries in children with bronchial asthma].
AB  - OBJECTIVE: To assess whether in children with asthma dental caries occurs more
      frequently and is more advanced than in healthy children of the same age.
      MATERIAL AND METHODS: The investigations were carried out in 64 patients
      suffering from asthma aged from 8 to 16 years. The control group consisted of 64
      healthy children. The medium period of duration of the illness is 10 years and
      the mean time of treatment is 7 years. The clinical examination of the mouth was
      carried out in accordance with WHO guidelines. The results were analyzed taking
      into account the division of patients into 2 subgroups: with mixed and permanent
      dentition. Statistical analysis was performed using StatSoft's Statistica 7.0
      software, using the Mann-Whitney U and Fisher test. RESULTS: In the subgroup of
      permanent dentition the frequency of decay was 87.80% in asthmatics and 82.92% in
      the control group (no statistical significance p>0.05), and caries intensity was
      6.0 and 4.9 respectively. Statistical analysis showed a significant difference in
      the intensity of caries between the total two groups of patients examined
      (p=0.02) and between the groups of girls in this subgroup (p=0.00). In the
      subgroup with mixed dentition, there was no statistically significant difference
      in the frequency and the intensity of caries between patients and the control s
      (p>0.05). CONCLUSION: Permanent teeth caries is more severe in children with
      asthma than in the control group. These patients must be considered as high
      caries risk and should have special dental care.

PMID- 24296451
TI  - [Bezoars - diagnostic problems based on own observations and literature review].
AB  - INTRODUCTION: Bezoars are concretions of human or vegetable fibers that
      accumulate in the gastrointestinal tract of humans and animals. Patients may
      remain asymptomatic for many years, and symptoms develop as bezoars increase in
      size to the point of obstruction or perforation. THE AIM OF THE STUDY WAS TO
      PRESENT: 3 cases of bezoars treated in our centre and review of the current
      knowledge about this disorder, emphasizing the diagnostic difficulties.
      CONCLUSIONS: Physicians should consider bezoars as a differential diagnosis of
      acute abdomen. As bezoars may remain asymptomatic for many years, monitoring of
      pathogenetic and predisposing factors is essential, in particular in compulsive
      disorders.

PMID- 24296452
TI  - The role and regulation of secretion of erythropoietin in pregnancy.
AB  - Although erythropoietin plays a significant role in human metabolism, relatively
      little attention has been devoted in scientific literature to its role and
      mechanisms regulating its secretion in pregnancy. The authors of this article
      discussed the following issues: - construction, biological role and regulation of
      erythropoietin secretion, - its extra-hematologic effect, - erythropoietin
      concentration in normal and complicated pregnancy, - erythropoietin secretion in
      placenta, including its effect on placental function, - the role of
      erythropoietin in evaluation of fetal well-being. What seems to be a particularly
      promising trend in further studies is popularizing the measurement of EPO
      concentration in cord blood or amniotic fluid as fetal hypoxia marker. 

PMID- 24296453
TI  - Optimization of positive end-expiratory pressure by volumetric capnography
      variables in lavage-induced acute lung injury.
AB  - BACKGROUND: In the acute respiratory distress syndrome (ARDS), lung-protective
      ventilation strategies combine the delivery of small tidal volumes (VT) with
      sufficient positive end-expiratory pressure (PEEP). However, an optimal approach
      guiding the setting of PEEP has not been defined. Monitoring volumetric
      capnography is useful to detect changes in lung aeration. OBJECTIVES: The aim of
      this study was to determine whether volumetric capnography may be a useful method
      to determine the optimal PEEP in ARDS. METHODS: In 8 lung-lavaged piglets, PEEP
      was reduced from 20 to 4 cm H2O in steps of 4 cm H2O every 10 min followed by
      full lung recruitment. Volumetric capnography, respiratory mechanics, blood gas
      analysis, hemodynamic data and whole-lung computed tomography scans were obtained
      at each PEEP level. RESULTS: After lung recruitment, end-expiratory lung volume
      progressively decreased from 1,160 +/- 273 ml at PEEP 20 cm H2O to 314 +/- 86 ml
      at PEEP 4 cm H2O. The ratio of alveolar dead space (VDalv) to alveolar VT (VTalv)
      and the phase III slope of volumetric capnography (SIII) reached a minimum at
      PEEP 16 cm H2O. At this PEEP level, overaerated lung regions were significantly
      reduced, nonaerated lung regions did not increase, and partial pressure of oxygen
      in arterial blood/fraction of inspired oxygen (P/F) and static respiratory system
      compliance (Crs) reached a maximum. At PEEP levels <16 cm H2O, nonaerated lung
      regions significantly increased, P/F and Crs deteriorated, and VDalv/VTalv and
      SIII began to increase. CONCLUSIONS: In this surfactant-depleted model, PEEP at
      the lowest VDalv/VTalv and SIII allows an optimal balance between lung
      overinflation and collapse. Hence, volumetric capnography is a useful bedside
      approach to identify the optimal PEEP.

PMID- 24296454
TI  - Enhanced efficiency of P-element mediated transgenesis in Drosophila:
      Microinjection of DNA complexed with nanomaterial.
AB  - The efficiency of genetic transformation technology to generate stable
      transgenics depends upon the successful delivery of plasmid DNA in embryonic
      cells. The available gene vectors facilitate efficient plasmid DNA delivery to
      the cellular milieu but are exposed to nuclease degradation. Recent in vitro
      studies suggest encapsulation of plasmid DNA with nanomaterial(s) for better
      protection against nucleases. Therefore, in this study, we tested if complexing
      of free plasmid DNA with linear polyethylenimine (LPEI, 25 kDa) based
      nanoparticle (LPN) enhances the efficiency of transformation (transgenesis) by
      using Drosophila based germ-line transformation technology. Here, we show that
      the LPN-DNA complex not only enhances the efficiency of this transgenic
      technology at a DNA concentration of 0.04 MUg/MUl but also reduces the DNA
      quantity required to generate transgenics by ten folds. This approach has
      potential applications for other types of transgenesis and nucleic acid injection
      methods in Drosophila as well as other popular genetic model systems. 

PMID- 24296455
TI  - 454 pyrosequencing analysis of bacterial diversity revealed by a comparative
      study of soils from mining subsidence and reclamation areas.
AB  - Significant alteration in the microbial community can occur across reclamation
      areas suffering subsidence from mining. A reclamation site undergoing
      fertilization practices and an adjacent coal-excavated subsidence site (sites A
      and B, respectively) were examined to characterize the bacterial diversity using
      454 high-throughput 16S rDNA sequencing. The dominant taxonomic groups in both
      the sites were Proteobacteria, Acidobacteria, Bacteroidetes, Betaproteobacteria,
      Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Deltaproteobacteria,
      Chloroflexi, and Firmicutes. However, the bacterial communities' abundance,
      diversity, and composition differed significantly between the sites. Site A
      presented higher bacterial diversity and more complex community structures than
      site B. The majority of sequences related to Proteobacteria, Gemmatimonadetes,
      Chloroflexi, Nitrospirae, Firmicutes, Betaproteobacteria, Deltaproteobacteria,
      and Anaerolineae were from site A; whereas those related to Actinobacteria,
      Planctomycetes, Bacteroidetes, Verrucomicrobia, Gammaproteobacteria,
      Nitriliruptoria, Alphaproteobacteria, and Phycisphaerae originated from site B.
      The distribution of some bacterial groups and subgroups in the two sites
      correlated with soil properties and vegetation due to reclamation practice. Site
      A exhibited enriched bacterial community, soil organic matter (SOM), and total
      nitrogen (TN), suggesting the presence of relatively diverse microorganisms. SOM
      and TN were important factors shaping the underlying microbial communities.
      Furthermore, the specific plant functional group (legumes) was also an important
      factor influencing soil microbial community composition. Thus, the effectiveness
      of 454 pyrosequencing in analyzing soil bacterial diversity was validated and an
      association between land ecological system restoration, mostly mediated by
      microbial communities, and an improvement in soil properties in coalmining
      reclamation areas was suggested.

PMID- 24296456
TI  - Enzymatic production of 15-hydroxyeicosatetraenoic acid from arachidonic acid by
      using soybean lipoxygenase.
AB  - 15-Hydroxyeicosatetraenoic acid (HETE), as a mammalian biologically active
      metabolite, has anticarcinogenic effect. The conditions of producing 15-HETE from
      arachidonic acid by using soybean lipoxygenase were optimal at pH 8.5 and 20
      degrees C with 9 g/l arachidonic acid, 54.4 U/ml soybean lipoxygenase, and 4%
      methanol. Under these optimized conditions, the enzyme produced 9.5 g/l 15-HETE
      after 25 min, with a molar conversion yield of 99% and a productivity of 22.8 g
      l(-1) h(-1). To the best of our knowledge, this is the first biotechnological
      production of 15-HETE.

PMID- 24296457
TI  - Effect of lipopolysaccharide (LPS) on mouse model of steroid-induced avascular
      necrosis in the femoral head (ANFH).
AB  - Avascular necrosis of the femoral head (ANFH) is commonly observed in patients
      treated with excessive glucocorticoid (GC). Single administration of
      lipopolysaccharide (LPS) has shown to induce immune stimulatory factors. However,
      the effect of repeated administration of LPS on GC-induced ANFH has not been
      studied. Thus, the purpose of this study was (i) to examine the cytokine profile
      induced by repeated LPS administrations and (ii) to test the effect of repeated
      LPS treatments on GC-induced ANFH. A mouse necrosis model of ANFH was designed by
      chronic GC administration with co-treatment of LPS. Mice body weights in the
      LPS/prednisolone (PDN) co-treated group were lower than that of the untreated
      control group, but spleen weights were greater than the control group. The levels
      of IL-6, TNFalpha, and IL-33 in the liver and spleen of the LPS/PDN group were
      lower than the untreated control group, whereas TNFalpha level in the femoral
      head of the LPS/PDN group increased. Collectively, the effect of repeated LPS on
      the pathogenesis of GC-induced ANFH was associated with the TNFalpha level in the
      femoral head, but the pathogenesis did not correspond to cytokine levels in
      immune tissues. 

PMID- 24296458
TI  - Glioblastoma-specific anticancer activity of pheophorbide a from the edible red
      seaweed Grateloupia elliptica.
AB  - The chlorophyll-related compound pheophorbide a (Pa) was successively purified
      from an edible red seaweed, Grateloupia elliptica, using silica, octadecyl silica
      column chromatography and reversed phase-high-performance liquid chromatography,
      as well as the cell cycle inhibitory and apoptotic effects of Pa being
      investigated in U87MG glioblastoma cells. The Pa exhibited strong anticancer
      effects in the absence of direct photo-irradiation against various cancer cell
      lines, including U87MG, SK-OV-3, and HeLa cells. Among the cancer cells, the
      strongest anticancer activity of Pa exhibited on U87MG cells with IC50 values of
      2.8 MUg/ml. In addition, Pa specifically had cytostatic activity on glioblastoma
      cells rather than human umbilical vein endothelial cells. Analysis of the cell
      cycle distribution showed that Pa induced G0/G1 arrest of U87 MG cells. In
      addition, arrested cells induced late apoptosis and DNA degradation under dark
      condition. These results suggest that Pa isolated from G. elliptica is a
      potential glioblastoma-specific anticancer agent without side effects on normal
      cells.

PMID- 24296459
TI  - Characterization of veterinary hospital-associated isolates of Enterococcus
      species in Korea.
AB  - Possible cross-transmission of hospital-associated enterococci between human
      patients, medical staff, and hospital environments has been extensively studied.
      However, limited information is available for veterinary hospital-associated
      Enterococcus isolates. This study investigated the possibility of cross
      transmission of antibiotic-resistant enterococci between dog patients, their
      owners, veterinary staff, and hospital environments. Swab samples (n =46 5) were
      obtained from five veterinary hospitals in Seoul, Korea, during 2011. Forty-three
      Enterococcus strains were isolated, representing seven enterococcal species. E.
      faecalis and E. faecium were the most dominant species (16 isolates each, 37.2%).
      Although slight differences in the antibiotic resistance profiles were observed
      between the phenotypic and the genotypic data, our antibiogram analysis
      demonstrated high prevalence of the multiple drug-resistant (MDR) isolates of E.
      faecalis (10/16 isolates, 62.5%) and E. faecium (12/16 isolates, 75.0%). Pulsed
      field gel electrophoretic comparison of the MDR isolates revealed three different
      clonal sets of E. faecalis and a single set of E. faecium, which were isolated
      from different sample groups or dog patients at the same or two separate
      veterinary hospitals. These results imply a strong possibility of cross
      transmission of the antibiotic-resistant enterococcal species between animal
      patients, owners, veterinary staff, and hospital environments. 

PMID- 24296460
TI  - Interaction of noradrenaline and cortisol predicts negative intrusive memories in
      posttraumatic stress disorder.
AB  - Recent evidence suggests that an interaction of noradrenaline (NE) and cortisol
      (CORT) during encoding leads to greater consolidation of emotional memories.
      Convergent models of posttraumatic stress disorder (PTSD) suggest the release of
      CORT and NE lead to greater intrusive memories in PTSD. This study examined the
      effect of NE and CORT during encoding on recall and intrusive memories in PTSD.
      Fifty-eight participants (18 participants with PTSD, 20 trauma-exposed controls,
      and 20 non-trauma exposed controls) provided saliva samples of NE (indexed by
      salivary alpha amylase; sAA) and CORT at (a) baseline and (b) after viewing
      negative emotional stimuli. Delayed memory recall and number of intrusive
      memories of negative, neutral and positive stimuli were recorded two days after
      this initial testing session. The PTSD group had greater NE levels to negative
      stimuli and reported greater numbers of intrusive memories of negative stimuli
      than controls. Regression analyses revealed that the interaction of CORT and NE
      significantly predicted negative intrusive memories in the PTSD group. The trauma
      exposed group reported significantly greater recall of negative images compared
      to controls, but did not differ significantly from the PTSD group. The PTSD group
      reported greater levels of suppression of negative images during encoding
      compared to the other groups. Our results confirm that the interaction of NE and
      CORT significantly predicts greater negative intrusive memories, but this occurs
      specifically in the PTSD group. This suggests that a level of heightened arousal
      is required for the relationship between stress hormones and emotional memory to
      manifest in PTSD. 

PMID- 24296461
TI  - Role of the insular cortex in taste familiarity.
AB  - Determining the role of the main gustatory cortical area within the insular
      cortex (IC), in conditioned taste aversion (CTA) has been elusive due to
      effective compensatory mechanisms that allow animals to learn in spite of lacking
      IC. IC lesions performed before CTA training induces mild if any memory
      impairments, while IC lesions done weeks after CTA produce amnesia. IC lesions
      before taste presentation have also been shown not to affect taste familiarity
      learning (attenuation of neophobia). This lack of effect could be either
      explained by compensation from other brain areas or by a lack of involvement of
      the IC in taste familiarity. To assess this issue, rats were bilaterally IC
      lesioned with ibotenic acid (200-300 nl.; 15 mg/ml) one week before or after
      taste familiarity, using either a preferred (0.1%) or a non-preferred (0.5%)
      saccharin solution. Rats lesioned before familiarity showed a decrease in
      neophobia to both solutions but no difference in their familiarity curve or their
      slope. When animals were familiarized and then IC lesioned, both IC lesioned
      groups treated the solutions as familiar, showing no differences from sham
      animals in their retention of familiarity. However, both lesioned groups showed
      increased latent inhibition (or impaired CTA) when CTA trained after repeated pre
      exposures. The role of the IC in familiarity was also assessed using temporary
      inactivation of the IC, using bilateral micro-infusions of sodium channel blocker
      bupivacaine before each of 3 saccharin daily presentations. Intra-insular
      bupivacaine had no effects on familiarity acquisition, but did impair CTA
      learning in a different group of rats micro-infused before saccharin presentation
      in a CTA training protocol. Our data indicate that the IC is not essentially
      involved in acquisition or retention of taste familiarity, suggesting regional
      dissociation of areas involved in CTA and taste familiarity.

PMID- 24296462
TI  - Irritable bowel syndrome, inflammatory bowel disease and the microbiome.
AB  - PURPOSE OF REVIEW: The review aims to update the reader on current developments
      in our understanding of how the gut microbiota impact on inflammatory bowel
      disease and the irritable bowel syndrome. It will also consider current efforts
      to modulate the microbiota for therapeutic effect. RECENT FINDINGS: Gene
      polymorphisms associated with inflammatory bowel disease increasingly suggest
      that interaction with the microbiota drives pathogenesis. This may be through
      modulation of the immune response, mucosal permeability or the products of
      microbial metabolism. Similar findings in irritable bowel syndrome have
      reinforced the role of gut-specific factors in this 'functional' disorder.
      Metagenomic analysis has identified alterations in pathways and interactions with
      the ecosystem of the microbiome that may not be recognized by taxonomic
      description alone, particularly in carbohydrate metabolism. Treatments targeted
      at the microbial stimulus with antibiotics, probiotics or prebiotics have all
      progressed in the past year. Studies on the long-term effects of treatment on the
      microbiome suggest that dietary intervention may be needed for prolonged
      efficacy. SUMMARY: The microbiome represents 'the other genome', and to
      appreciate its role in health and disease will be as challenging as with our own
      genome. Intestinal diseases occur at the front line of our interaction with the
      microbiome and their future treatment will be shaped as we unravel our
      relationship with it.

PMID- 24296463
TI  - Gastrointestinal regulatory peptides and their receptors.

PMID- 24296464
TI  - Assessing auditory processing disorders in children with developmental dyslexia
      using auditory cognitive event-related potentials.
AB  - OBJECTIVES: It has been suggested that dyslexia is linked to a core cognitive
      deficit in phonological awareness tasks and/or in the processing of auditory
      stimuli. Auditory evoked potentials are a valid, objective measure of the
      accuracy of central auditory processing in humans. The aim of this study was to
      assess auditory evoked potentials in children with dyslexia. PATIENTS AND
      METHODS: Sixty-six children participated in the study. A set of hearing tests and
      the recording of complex event-related potentials (ERPs) were performed. RESULTS:
      Mixmatch negativity (MMN) and P300 waves were significantly more frequent in the
      healthy children (control group) than in children with dyslexia. The P300 wave
      was present in all subjects from the control group, the MMN wave in 92% of them.
      In the dyslexic group, complex ERPs were recorded roughly 33% of the time.
      Latencies of complex ERPs in children with dyslexia were greater than latencies
      in children in the control group. MMN and P300 maturation (change with age) was
      observed only for the control group. A wide range of MMN and P300 responses was
      observed across children with dyslexia. CONCLUSION: Complex ERPs may be useful in
      determining the condition of audiologic functions; however, on their own they are
      not sufficient to recognize dyslexia because of the heterogeneity of nonspecific
      changes.

PMID- 24296465
TI  - The nature of electronic excitations at the metal-bioorganic interface
      illustrated on histidine-silver hybrids.
AB  - We present a joint theoretical and experimental study of the structure selective
      optical properties of cationic and anionic histidine-silver complexes with Ag and
      Ag3 which were prepared in the gas phase using mass spectroscopy coupled to
      electrospray ion source. Our TDDFT calculations provide general insight into the
      nature of electronic excitations at the metal-bioorganic interface that involve
      pi-pi* excitation within bioorganic subunits, charge transfer between two
      subunits and intrametallic excitations. The binding of silver to histidine, one
      of the most important amino acids, induces red shift in the optical absorption of
      protonated histidine particularly for anionic species. The presence of the
      smallest metallic subunit Ag3 increases the intensity of low energy transitions
      of histidine illustrating a metal cluster-induced enhancement of absorption of
      biomolecules in hybrid systems. Comparison of calculated absorption spectra with
      experimental photofragmentation yield provides structural assignment of the
      measured spectroscopic patterns. Our findings may serve to establish silver
      labeling as the tool for the detection of histidine or histidine-tagged proteins.

PMID- 24296466
TI  - Violence against Deaf women: effect of partner hearing status.
AB  - Using a sample of Deaf female undergraduate students, the current study sought to
      investigate the prevalence, correlates, and characteristics of intimate partner
      violence victimization in hearing-Deaf and Deaf-Deaf relationships. Initial
      results suggest that similarities in hearing status and communication preference
      are associated with increased levels of negotiation within these relationships.
      However, compatibility in these areas did not co-occur with significant decreases
      in physical, psychological, or sexual partner violence. Recommendations for
      future research as well as implications for clinical and educational practice are
      outlined. 

PMID- 24296467
TI  - Close covalent contacts: gauging molecular compression in a molecular compression
      chamber.
AB  - A computational investigation is carried out on a 3-fold symmetric model
      molecular compression chamber comprising two triply-bridged triptycenes with
      variable endo-pointing substituents. Assessment of the strain of the constant
      scaffold serves to gauge the compression stress across variable interaction
      partners at unusually short C-X distance, and creates a transferable knowledge
      base for the design of molecules with close contacts due to bond length
      compression. Results motivate ideas in the design of more effective molecular
      compression chambers and their realization through chemical synthesis. 

PMID- 24296468
TI  - Characterization of African bat henipavirus GH-M74a glycoproteins.
AB  - In recent years, novel henipavirus-related sequences have been identified in bats
      in Africa. To evaluate the potential of African bat henipaviruses to spread in
      non-bat mammalian cells, we compared the biological functions of the surface
      glycoproteins G and F of the prototype African henipavirus GH-M74a with those of
      the glycoproteins of Nipah virus (NiV), a well-characterized pathogenic member of
      the henipavirus genus. Glycoproteins are central determinants for virus tropism,
      as efficient binding of henipavirus G proteins to cellular ephrin receptors and
      functional expression of fusion-competent F proteins are indispensable
      prerequisites for virus entry and cell-to-cell spread. In this study, we analysed
      the ability of the GH-M74a G and F proteins to cause cell-to-cell fusion in
      mammalian cell types readily permissive to NiV or Hendra virus infections. Except
      for limited syncytium formation in a bat cell line derived from Hypsignathus
      monstrosus, HypNi/1.1 cells, we did not observe any fusion. The highly restricted
      fusion activity was predominantly due to the F protein. Whilst GH-M74a G protein
      was found to interact with the main henipavirus receptor ephrin-B2 and induced
      syncytia upon co-expression with heterotypic NiV F protein, GH-M74a F protein did
      not cause evident fusion in the presence of heterotypic NiV G protein. Pulse
      chase and surface biotinylation analyses revealed delayed F cleavage kinetics
      with a reduced expression of cleaved and fusion-active GH-M74a F protein on the
      cell surface. Thus, the F protein of GH-M74a showed a functional defect that is
      most likely caused by impaired trafficking leading to less efficient proteolytic
      activation and surface expression. 

PMID- 24296470
TI  - Improving Our Ability to Evaluate Underlying Mechanisms of Behavioral Onset and
      Other Event Occurrence Outcomes: A Discrete-Time Survival Mediation Model.
AB  - The purpose of this article is to introduce and describe a statistical model that
      researchers can use to evaluate underlying mechanisms of behavioral onset and
      other event occurrence outcomes. Specifically, the article develops a framework
      for estimating mediation effects with outcomes measured in discrete-time epochs
      by integrating the statistical mediation model with discrete-time survival
      analysis. The methodology has the potential to help strengthen health research by
      targeting prevention and intervention work more effectively as well as by
      improving our understanding of discretized periods of risk. The model is applied
      to an existing longitudinal data set to demonstrate its use, and programming code
      is provided to facilitate its implementation. 

PMID- 24296471
TI  - Evidence-based health care management: what is the research evidence available
      for health care managers?
AB  - In light of increasing interest in evidence-based management, we conducted a
      scoping review of systematic reviews (SRs) and meta-analyses (MAs) to determine
      the availability and accessibility of evidence for health care managers; 14 MAs
      and 61 SRs met the inclusion criteria. Most reviews appeared in medical journals
      (53%), originated in the United States (29%) or United Kingdom (22%), were
      hospital-based (55%), and targeted clinical providers (55%). Topics included
      health services organization (34%), quality/patient safety (17%), information
      technology (15%), organization/workplace management (13%), and health care
      workforce (12%). Most reviews addressed clinical topics of relevance to managers;
      management-related interventions were rare. The management issues were mostly
      classified as operational (65%). Surprisingly, 96.5% of search results were not
      on target. A better classification within PubMed is needed to increase the
      accessibility of meaningful resources and facilitate evidence retrieval. Health
      care journals should take initiatives encouraging the publication of reviews in
      relevant management areas. 

PMID- 24296469
TI  - Novel hepatitis E like virus found in Swedish moose.
AB  - A novel virus was detected in a sample collected from a Swedish moose (Alces
      alces). The virus was suggested as a member of the Hepeviridae family, although
      it was found to be highly divergent from the known four genotypes (gt1-4) of
      hepatitis E virus (HEV). Moose are regularly hunted for consumption in the whole
      of Scandinavia. Thus, the finding of this virus may be important from several
      aspects: (a) as a new diverged HEV in a new animal species, and (b) potential
      unexplored HEV transmission pathways for human infections. Considering these
      aspects, we have started the molecular characterization of this virus. A 5.1 kb
      amplicon was sequenced, and corresponded to the partial ORF1, followed by
      complete ORF2, ORF3 and poly(A) sequence. In comparison with existing HEVs, the
      moose HEV genome showed a general nucleotide sequence similarity of 37-63% and an
      extensively divergent putative ORF3 sequence. The junction region between the
      ORFs was also highly divergent; however, two putative secondary stem-loop
      structures were retained when compared to gt1-4, but with altered structural
      appearance. In the phylogenetic analysis, the moose HEV deviated and formed its
      own branch between the gt1-4 and other divergent animal HEVs. The
      characterization of this highly divergent genome provides important information
      regarding the diversity of HEV infecting various mammalian species. However,
      further studies are needed to investigate its prevalence in the moose populations
      and possibly in other host species, including the risk for human infection.

PMID- 24296472
TI  - Is super-resolution microscopy right for you?

PMID- 24296473
TI  - Genomics: the state of the art in RNA-seq analysis.

PMID- 24296475
TI  - The combination of fludarabine, cytarabine and etoposide is an active and well
      tolerated regimen in relapsed/refractory acute myeloid leukemia.
AB  - We retrospectively reviewed the outcome of 20 consecutive subjects with
      refractory/relapsed acute myeloid leukemia (AML; 9 refractory and 11 relapsed)
      treated at our institution with a fludarabine, cytarabine and etoposide (FCE)
      salvage regimen. Of 20 patients with refractory/relapsed AML, 15 (75%) achieved
      complete remission (CR)/CR with incomplete peripheral blood count recovery (CRi),
      including 14 CR and 1 CRi. The 4- and 8-week treatment-related mortality (TRM)
      for all patients during reinduction was 0 and 5%, respectively. Eight of 15
      patients (53%) who successfully achieved CR were able to undergo allogeneic
      hematopoietic stem cell transplantation with a 0% non-relapse mortality rate. FCE
      is a new, well-tolerated, anthracycline-free regimen, which has a promising
      activity in relapsed/refractory AML and is associated with low TRM in this high
      risk population.

PMID- 24296474
TI  - Using networks to measure similarity between genes: association index selection.
AB  - Biological networks can be used to functionally annotate genes on the basis of
      interaction-profile similarities. Metrics known as association indices can be
      used to quantify interaction-profile similarity. We provide an overview of
      commonly used association indices, including the Jaccard index and the Pearson
      correlation coefficient, and compare their performance in different types of
      analyses of biological networks. We introduce the Guide for Association Index for
      Networks (GAIN), a web tool for calculating and comparing interaction-profile
      similarities and defining modules of genes with similar profiles. 

PMID- 24296476
TI  - Stearic acid serves as a potent inhibitor of protein tyrosine phosphatase 1B.
AB  - BACKGROUND/AIMS: Free fatty acids (FFAs) are implicated in diverse signal
      transduction pathways. The present study investigated the effects of the
      saturated FFA stearic acid on protein tyrosine phosphatase 1B (PTP1B) activity,
      Akt activity, and glucose uptake into cells relevant to insulin signal. METHODS:
      PTP1B activity was assayed under the cell-free conditions. Phosphorylation of
      insulin receptor and Akt and glucose uptake into cells were monitored in
      differentiated 3T3-L1-GLUT4myc adipocytes. RESULTS: In the cell-free PTP1B assay,
      stearic acid suppressed PTP1B activity in a concentration (1-30 MUM)-dependent
      manner. For 3T3-L1- GLUT4myc adipocytes insulin phosphorylated insulin receptor
      at Tyr1185 and Akt at Thr308 and Ser473 in a concentration (100 fM-100 nM)
      dependent manner and stimulated glucose uptake into cells in a concentration (0.1
      100 nM)-dependent manner. Stearic acid (30 MUM) significantly increased insulin
      induced phosphorylation of insulin receptor at Tyr1185, but insulin-induced
      phosphorylation of Akt was not significantly enhanced. Stearic acid (30 MUM) by
      itself promoted glucose uptake into adipocytes. CONCLUSION: The results of the
      present study indicate that stearic acid serves as a potent PTP1B inhibitor,
      possibly causing an enhancement in the insulin receptor signaling to stimulate
      glucose uptake into adipocytes.

PMID- 24296477
TI  - Suppression of the two-dimensional electron gas in LaGaO3/SrTiO3 by cation
      intermixing.
AB  - Cation intermixing at the n-type polar LaGaO3/SrTiO3 (001) interface is
      investigated by first principles calculations. Ti<=>Ga, Sr<=>La, and SrTi<=>LaGa
      intermixing are studied in comparison to each other, with a focus on the
      interface stability. We demonstrate in which cases intermixing is energetically
      favorable as compared to a clean interface. A depopulation of the Ti 3dxy
      orbitals under cation intermixing is found, reflecting a complete suppression of
      the two-dimensional electron gas present at the clean interface. 

PMID- 24296478
TI  - An anthropometric analysis of the head and face in vocal students.
AB  - OBJECTIVES: The aim of the study was an anthropometric analysis of the values of
      selected cranial and facial indexes in vocal students and a comparison of these
      values with the standards for the same ethnic and age group of non-singing
      students. PATIENTS AND METHODOLOGY: 56 vocal students, aged 19-26 years, were
      examined. Standard instruments, such as sliding and spreading callipers and soft
      measuring tape, were used for the examination. A set of 32 linear measurements of
      the head and face was provided. RESULTS: In all head measurements the obtained
      results were greater for the vocal students. The vocal students revealed greater
      values of the indexes related to face width and depth of the lower jaw. In the
      comparison group the indices for the middle and lower part of the face were
      significantly higher. CONCLUSION: Vocalists have bigger heads and mandibles than
      non-singers.

PMID- 24296479
TI  - rhBMP-2 for posterolateral instrumented lumbar fusion: a multicenter prospective
      randomized controlled trial.
AB  - STUDY DESIGN: Multicenter randomized controlled trial. OBJECTIVE: To evaluate the
      effect of recombinant human bone morphogenetic protein (rhBMP-2) on
      radiographical fusion rate and clinical outcome for surgical lumbar arthrodesis
      compared with iliac crest autograft. SUMMARY OF BACKGROUND DATA: In many types of
      spinal surgery, radiographical fusion is a primary outcome equally important to
      clinical improvement, ensuring long-term stability and axial support. Biologic
      induction of bone growth has become a commonly used adjunct in obtaining this
      objective. We undertook this study to objectify the efficacy of rhBMP-2 compared
      with traditional iliac crest autograft in instrumented posterolateral lumbar
      fusion. METHODS: Patients undergoing 1- or 2-level instrumented posterolateral
      lumbar fusion were randomized to receive either autograft or rhBMP-2 for their
      fusion construct. Clinical and radiographical outcome measures were followed for
      2 to 4 years postoperatively. RESULTS: One hundred ninety seven patients were
      successfully randomized among the 8 participating institutions. Adverse events
      attributable to the study drug were not significantly different compared with
      controls. However, the control group experienced significantly more graft-site
      complications as might be expected. 36-Item Short Form Health Survey, Oswestry
      Disability Index, and leg/back pain scores were comparable between the 2 groups.
      After 4 years of follow-up, radiographical fusion rates remained significantly
      higher in patients treated with rhBMP-2 (94%) than those who received autograft
      (69%) (P = 0.007). CONCLUSION: The use of rhBMP-2 for instrumented posterolateral
      lumbar surgery significantly improves the chances of radiographical fusion
      compared with the use of autograft. However, there is no associated improvement
      in clinical outcome within a 4-year follow-up period. These results suggest that
      use of rhBMP-2 should be considered in cases where lumbar arthrodesis is of
      primary concern.

PMID- 24296480
TI  - Histological study of chordoma origin from fetal notochordal cell rests.
AB  - STUDY DESIGN: The histological comparative study was performed on chordoma and
      notochordal cell rests (NCRs). OBJECTIVE: To understand the histological
      similarity and homology of chordoma and NCRs, further supplying direct evidence
      of chordoma origin from NCRs. SUMMARY OF BACKGROUND DATA: Although many studies
      supported the hypothesis that chordoma arise from NCRs, there has been little
      direct evidence reported to date. Of the base of our previous study, we conducted
      a comparative histological study among NCRs coexisting in chordoma, fetal NCRs,
      and chordoma tumor components. METHODS: Thirty fetal nucleus pulposus and 46
      chordoma specimens were harvested, and classic chordoma tumor markers and
      brachyury expression levels were investigated through immunohistochemical method.
      RESULTS: The fetal NCRs existed in the form of clusters in the center of nucleus
      pulposus <36 gestational weeks; NCRs coexisting in chordoma specimens consisted
      of packed cells without extracellular myxoid matrix. Both the above-mentioned
      NCRs as well as chordoma tumor components showed high sensitivity for classic
      chordoma tumor makers (epithelial membrane antigen, AE1/AE3, CAM5.2, vimentin, S
      100); both kinds of NCRs showed completely negative expression for brachyury,
      whereas chordoma tumor components demonstrated 100% positivity. CONCLUSION: Our
      study results supported histological similarity and homology of NCRs coexisting
      in chordoma and in fetal nucleus pulposus. Brachyury activation probably takes an
      important role in chordoma tumoregenesis.

PMID- 24296481
TI  - No relationship between body mass index and changes in pain and disability after
      exercise rehabilitation for patients with mild to moderate chronic low back pain.
AB  - STUDY DESIGN: A retrospective multicenter study. OBJECTIVE: To investigate the
      relationship between body mass index (BMI) and changes in pain and disability
      resulting from exercise-based chronic low back pain (cLBP) treatment. SUMMARY OF
      BACKGROUND DATA: Past research has shown evidence of a relationship between BMI,
      a measurement of obesity, and cLBP. Exercise is a known beneficial treatment for
      cLBP. However, it is unclear if exercise-induced changes in pain and disability
      are related to baseline levels of, or changes in, BMI. METHODS: One hundred and
      twenty-eight (n = 128) males and females with cLBP performed 8 weeks of exercise,
      consisting of 3 to 5 exercise sessions (minimum of 1 supervised session) per
      week. Outcome measures included BMI and self-reported pain and disability. BMI
      was calculated as weight divided by height squared (kg/m). Pain was measured
      using the visual analogue scale and disability was measured using the Oswestry
      Disability Index. Correlation, regression, covariance and likelihood ratios
      analyses were used to examine the relationship between BMI and self-reported pain
      and disability changes. RESULTS: No baseline relationships between BMI and self
      reported pain (r = -0.083, P = 0.349) and disability (r = 0.090, P = 0.314) were
      observed. There was no relationship observed between baseline BMI (P = 0.938, P =
      0.873), or changes in BMI (P = 0.402, P = 0.854), with exercise-related changes
      in pain and disability, respectively. No relationships between baseline BMI or
      BMI changes with pain and disability at baseline or after exercise were observed
      on the basis of pain and disability subgroups. BMI was not a predictor of
      exercise-based pain and disability changes. CONCLUSION: There was no significant
      relationship between BMI and self-reported pain and disability in cLBP
      participants. BMI was not a predictor of exercise-induced changes in pain and
      disability. The reliance on BMI as a sole measurement of obesity in cLBP research
      may be unwarranted.

PMID- 24296482
TI  - Preoperative narcotic use and its relation to depression and anxiety in patients
      undergoing spine surgery.
AB  - STUDY DESIGN: Prospective review of registry data at a single institution from
      October 2010 to June 2012. OBJECTIVE: To assess whether the amount of
      preoperative narcotic use is associated with preoperative depression and anxiety
      in patients undergoing spine surgery for a structural lesion. SUMMARY OF
      BACKGROUND DATA: Previous work suggests that narcotic use and psychiatric
      comorbidities are significantly related. Among other psychological
      considerations, depression and anxiety may be associated with the amount of
      preoperative narcotic use in patients undergoing spine surgery. METHODS: Five
      hundred eighty-three patients undergoing lumbar (60%), thoracolumbar (11%), or
      cervical spine (29%) were included. Self-reported preoperative narcotic
      consumption was obtained at the initial preoperative visit and converted to daily
      morphine equivalent amounts. Preoperative Zung Depression Scale (ZDS) and
      Modified Somatic Perception Questionnaire (MSPQ) scores were also obtained at the
      initial preoperative visit and recorded as measures of depression and anxiety,
      respectively. Resistant and robust bootstrapped multivariable linear regression
      analysis was performed to determine the association between ZDS and MSPQ scores
      and preoperative narcotics, controlling for clinically important covariates. Mann
      Whitney U tests examined preoperative narcotic use in patients who were
      categorized as depressed (ZDS >= 33) or anxious (MSPQ >= 12). RESULTS:
      Multivariable analysis controlling for age, sex, smoking status, preoperative
      employment status, and prior spinal surgery demonstrated that preoperative ZDS (P
      = 0.006), prior spine surgery (P = 0.007), and preoperative pain (0.014) were
      independent risk factors for preoperative narcotic use. Preoperative MSPQ (P =
      0.083) was nearly a statistically significant risk factor. Patients who were
      categorized as depressed or anxious on the basis of ZDS and MSPQ scores also
      showed higher preoperative narcotic use than those who were not (P < 0.0001).
      CONCLUSION: Depression and anxiety as assessed by ZDS and MSPQ scores were
      significantly associated with increased preoperative narcotic use, underscoring
      the importance of thorough psychological and substance use evaluation in patients
      being evaluated for spine surgery.

PMID- 24296483
TI  - In vivo discography in degenerate porcine spines revealed pressure transfer to
      adjacent discs.
AB  - STUDY DESIGN: In vivo experimental porcine study. OBJECTIVE: To investigate if
      discography induced pressure increase in adjacent degenerate discs. SUMMARY OF
      BACKGROUND DATA: Despite refinements in the past 2 decades, the validity of
      discography is debated. Discography in healthy pigs has shown that the pressure
      increase during disc injection transmits to adjacent discs, a potential source
      for false positive responses. METHODS: Degeneration in 1 lumbar disc was induced
      in 10 pigs by drilling a hole through the endplate. Intradiscal pressure was
      recorded using a 0.36-mm fiber-optic pressure transducer inserted into nucleus
      pulposus through a 22-gauge needle. The pressure was measured simultaneously in 2
      adjacent discs during slow (0.03 mL/s) automated contrast injection into 1 of the
      discs up to 8 bar (116 psi). Ten adjacent discs were prefilled with contrast from
      previous discogram. A pressure increase 2 psi or more above baseline was defined
      as increased pressure in adjacent discs. Pressure was recorded until 15 minutes
      after injection. RESULTS: A total of 28 discograms were successfully performed. A
      pressure increase during injection was detected in 57% (16) of the 28 adjacent
      discs with mean 3.2 psi (1.7-8.2; standard deviation, 1.8), corresponding to a
      mean increase above baseline of 11%. Of those 16 adjacent discs, 4 were
      nondegenerate and 12 degenerate, of which 7 were prefilled. Fifteen minutes after
      injection, 89% of adjacent discs displayed increase in pressure of mean 14% above
      baseline. CONCLUSION: Discography induced pressure increase in adjacent discs in
      a degenerate disc model, something not reported earlier. If present, also in
      human spine pressure transmission, may be a potential cause for false positive
      discography responses.

PMID- 24296484
TI  - Aggrecan variable number of tandem repeat polymorphism and lumbar disc
      degeneration: a meta-analysis.
AB  - STUDY DESIGN: Data on the association between the ACAN (encoded for aggrecan core
      protein) variable number of tandem repeat (VNTR) polymorphism and lumbar disc
      degeneration are conflicting, so we performed a meta-analysis. OBJECTIVE:
      Aggrecan is involved in the shock absorbing function of the lumbar disc; we
      performed a meta-analysis to assess the association between ACAN VNTR and lumbar
      degeneration. SUMMARY OF BACKGROUND DATA: To perform a meta-analysis, we searched
      for studies published until September 2012, using electronic databases (PubMed,
      EMBASE, and China National Knowledge Infrastructure). Eight studies involving 965
      cases of lumbar disc degeneration and 982 control subjects were identified.
      METHODS: Assessment for eligibility and extraction of data were performed by 2
      independent investigators. We extracted allele frequency for each study. We
      calculated the pooled odds ratios (ORs) and 95% confidence intervals (CI) to
      assess the strength of the association between the ACAN VNTR polymorphism and
      lumbar disc degeneration risk. RESULTS: Results from the allele model suggested
      an increased risk of lumbar disc degeneration for the shorter alleles carriers
      compared with the normal alleles and longer alleles (OR = 1.54, 95% CI: 1.04
      2.30, P = 0.03). In subgroup analysis by ethnicity, significant increased risks
      were found among Asians with shorter alleles (OR=1.65, 95% CI: 1.17-2.33, P =
      0.004). CONCLUSION: Our results suggest an increased risk of shorter alleles
      compared with normal alleles and longer alleles against lumbar disc degeneration
      among populations especially among Asian descent. Such association may not be
      statistically significant in European populations.

PMID- 24296485
TI  - High latency of tuberculosis manifestation in a premature extremely low birth
      weight infant with favorable outcome.
AB  - We report a case of possible congenital tuberculosis in a 22+2 weeks, 460 g,
      vaginally delivered female infant born to a mother suffering from tuberculous
      endometritis, diagnosed soon after delivery. At 156 days of age, Mycobacterium
      tuberculosis was detected via PCR from the infant's gastric juice and was
      subsequently isolated. There was no evidence for horizontal transmission. Mother
      and child were treated successfully. This case illustrates the possibility of
      significant latency between infection and clinical manifestation in preterm
      infants and also emphasizes the need for urgent treatment of neonates in such
      situations.

PMID- 24296486
TI  - SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK.
AB  - Efficient coupling of cellular energy production to metabolic demand is crucial
      to maintain organismal homeostasis. Here, we report that the mitochondrial
      Sirtuin Sirt4 regulates mitochondrial ATP homeostasis. We find that Sirt4 affects
      mitochondrial uncoupling via the adenine nucleotide translocator 2 (ANT2). Loss
      of Sirt4 expression leads to decreased cellular ATP levelsin vitro and in vivo
      while Sirt4 overexpression is associated with increased ATP levels. Further, we
      provide evidence that lack of Sirt4 activates a retrograde signaling response
      from the mitochondria to the nucleus that includes AMPK, PGC1alpha, key
      regulators of beta-oxidation such as Acetyl-CoA carboxylase, and components of
      the mitochondrial respiratory machinery. This study highlights the ability of
      Sirt4 to regulate ATP levels via ANT2 and a feedback loop involving AMPK.

PMID- 24296488
TI  - SHON is a novel estrogen-regulated oncogene in mammary carcinoma that predicts
      patient response to endocrine therapy.
AB  - Endocrine therapies are the primary systemic intervention for patients with
      estrogen receptor-positive (ER(+)) breast cancer. However, a significant
      proportion of initially responsive ER(+) tumors develop resistance, with relapses
      occurring in up to 50% of patients. Lack of reliable predictive biomarkers
      remains an unfilled need for enhanced clinical management of this disease. In
      this study, we address this need in identifying a novel estrogen-regulated gene
      called SHON (secreted hominoid-specific oncogene). Enforced expression of SHON in
      breast cancer cells increased their proliferation, survival, migration, and
      invasion in vitro. Furthermore, SHON enhanced the oncogenicity of these cells in
      xenograft models of human breast cancer and was also sufficient to oncogenically
      transform MCF10A human mammary epithelial cells. Conversely, SHON attenuation
      mediated by RNA interference- or antibody-based methods reduced the oncogenicity
      of breast cancer cells. Mechanistic investigations indicated that the oncogenic
      transforming properties of SHON were mediated by BCL-2 and NF-kappaB. In primary
      clinical specimens, SHON was immunohistochemically detected in 62% of breast
      cancers, in which its expression was positively correlated with ER expression. In
      this setting, SHON expression predicted a favorable response to endocrine therapy
      in high-risk patients with ER(+) breast cancer. Taken together, our findings
      identify SHON as a novel human oncogene with predictive utility in ER(+) breast
      cancer, perhaps offering a simple biomarker to predict the therapeutic efficacy
      of antiestrogen therapy in patients with breast cancer.

PMID- 24296489
TI  - The role of squash cytology in rapid on-site adequacy checking and rapid
      diagnosis in image-guided gun biopsy at a tertiary cancer center.
AB  - OBJECTIVE: To evaluate the role of squash cytology in rapid on-site adequacy
      checking (ROSAC) of image-guided gun biopsy and to determine its diagnostic
      accuracy at a tertiary cancer center. STUDY DESIGN: This was a prospective study
      on 183 patients undergoing image-guided biopsy. Squash smears were prepared from
      biopsy cores and checked for adequacy by cytotechnologists. When adequate, more
      cores were sampled from the same area for histopathology. If inadequate, the
      procedure was repeated at the same sitting on a different area. The squash smears
      were reported by cytopathologists within 4 h after staining with conventional
      Papanicoloau stain. The results were compared with the final histopathology
      report. RESULTS: The sampling was representative in 95.6% cases with concordance
      for adequacy in 97.3% cases. The sensitivity, specificity, positive predictive
      value and negative predictive value of squash cytology for diagnosis of the
      lesion were 99.4, 92.7, 97.7 and 97.4%, respectively. CONCLUSIONS: Squash
      cytology is an ideal and cost-effective technique for ROSAC of image-guided
      biopsies, which ensures adequacy, avoids repeat procedures and prevents delay in
      diagnosis. It can be effectively performed by trained cytotechnologists in
      radiology clinics. Squash cytology is also a cost-effective tool offering rapid
      diagnosis which expedites planning of treatment.

PMID- 24296490
TI  - HLA-haploidentical donor lymphocyte infusions for patients with relapsed
      hematologic malignancies after related HLA-haploidentical bone marrow
      transplantation.
AB  - Treatment of relapse after related HLA-haploidentical T cell-replete bone marrow
      transplantation (haploBMT) with post-transplantation cyclophosphamide (PTCy)
      using haploidentical donor lymphocyte infusion (haploDLI) is not documented. All
      patients who received haploDLI after haploBMT with PTCy between June 2003 and
      October 2012 were identified and assessed for graft-versus-host disease (GVHD)
      and outcomes. Forty patients received 52 haploDLI doses. Sixteen patients had
      acute myeloid leukemia, 11 had lymphomas, and 34 had nonmyeloablative
      conditioning before haploBMT. The median time from haploBMT to relapse was 183
      (range, 0 to 1399) days. The median age at haploDLI was 48 (range, 3 to 70)
      years. The first haploDLI doses were 1 * 10(5) CD3(+) cells/kg with subsequent
      escalation. The most commonly used first haploDLI dose was 1 * 10(6) CD3(+)
      cells/kg. The median follow-up after haploDLI was 7 (mean, 15.4; range, .5 to 96)
      months for the entire cohort, and 17.5 (mean, 28; range, 2.4 to 96) months for
      the responders. Acute GVHD developed in 10 patients (25%), 6 patients had grade 3
      to 4, and 3 developed chronic GVHD. Twelve (30%) patients achieved a complete
      response (CR) with a median duration of 11.8 (mean, 22.5; range, .4 to 94)
      months. At last follow-up, 8 responders were alive in CR; 6 for over a year.
      HaploDLI for relapse after haploBMT is associated with acceptable toxicities and
      can result in durable responses.

PMID- 24296491
TI  - Secondary monoclonal gammopathy of undetermined significance is frequently
      associated with high response rate and superior survival in patients with plasma
      cell dyscrasias.
AB  - Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special
      phenomenon that occurs during the treatment of multiple myeloma (MM). The
      incidence, biological characteristics, and prognostic value of secondary MGUS in
      patients with MM remain undefined. We proceed with a retrospective systematic
      review of serum immunofixation electrophoresis studies performed in 438 cases of
      patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM
      and 29 cases of primary plasma cell leukemia. Secondary MGUS was more common in
      patients with myeloma who had undergone stem cell transplantation than in those
      who had not (17 [29.8%] of 57 versus 5 [1.4%] of 352, P < .001). The clinical
      parameters and cytogenetic characteristics in patients with or without secondary
      MGUS were comparable. The complete response rates in patients with or without
      secondary MGUS were 81.8% and 21.8% respectively (P < .01). For the cohort as a
      whole, secondary MGUS was associated with significantly prolonged progression
      free survival (median, 52.0 months versus 22.5 months; P = .002) and overall
      survival (median, not reached versus 35.0 months; P < .001). The presence of
      secondary MGUS retained independent prognostic value with a moderate impact on
      overall survival (hazard ratio .128 [95% confidence interval .018 to .922]; P =
      .041) in the multivariate Cox regression model. However, when analysis was
      restricted to patients undergoing stem cell transplantation, no statistical
      differences in progression-free survival and overall survival were found. In
      conclusion, we observe that secondary MGUS was frequently observed in MM patients
      after transplantation and conferred a survival prolongation. The favorable
      survival in patients with secondary MGUS may be explained by beneficial effect
      from myeloablative therapy.

PMID- 24296493
TI  - Evaluation of GeneXpert MTB/RIF for the detection of Mycobacterium tuberculosis
      and resistance to rifampin in clinical specimens.
AB  - OBJECTIVES: GeneXpert (GX) is a novel real-time polymerase chain reaction assay
      for the simultaneous detection of Mycobacterium tuberculosis (MTB) and resistance
      to rifampin (RIF). We evaluated the performance of GX for direct detection of MTB
      in respiratory and non-respiratory specimens and assessed the ability of the
      assay to detect resistance to RIF in non-tuberculosis (TB) endemic country.
      METHODS: We analyzed 595 clinical samples in a 1550-bed tertiary hospital in
      Madrid, Spain. Specimens were processed using GX, auramine smear, conventional
      culture, and drug phenotypic susceptibility testing (DST) with MGIT SIRE (BD).
      RESULTS: Of the 595 clinical samples, 305 (51.3%) were non-respiratory and 290
      (48.7%) were respiratory. In total, MTB was isolated in 81 specimens, 71 of which
      were positive with GX. The sensitivity, specificity, PPV, and NPV of the GX were:
      97.1%, 98.6%, 95.7% and 99.1% for respiratory samples and 33.3%, 99.7%, 80.0% and
      97.3% for non-respiratory. GX detected 8 RIF-resistant samples, but only 5 were
      confirmed by DST. CONCLUSIONS: GX is an accurate, easy-to-apply and rapid test to
      detect MTB, especially in smear-positive respiratory samples. Although is a
      useful tool for the rapid identification of RIF-resistant MTB strains, the
      rifampin resistant results should be confirmed by DST.

PMID- 24296492
TI  - A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood
      transplantation in children with nonmalignant diseases.
AB  - Reduced-intensity conditioning (RIC) regimens have the potential to decrease
      transplantation-related morbidity and mortality. However, engraftment failure has
      been prohibitively high after RIC unrelated umbilical cord blood transplantation
      (UCBT) in chemotherapy-naive children with nonmalignant diseases (NMD). Twenty
      two children with a median age of 2.8 years, many with severe comorbidities and
      prior viral infections, were enrolled in a novel RIC protocol consisting of
      hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single
      UCBT. Patients underwent transplantation for inherited metabolic disorders (n =
      8), primary immunodeficiencies (n = 9), hemoglobinopathies (n = 4) and Diamond
      Blackfan anemia (n = 1). Most umbilical cord blood (UCB) units were HLA
      mismatched with median infused total nucleated cell dose of 7.9 * 10(7)/kg. No
      serious organ toxicities were attributable to the regimen. The cumulative
      incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65%
      to 100%) in a median of 20 days, with the majority sustaining > 95% donor
      chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease
      (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%)
      and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive
      chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were
      viral infections (n = 3), acute GVHD (n = 1) and transfusion reaction (n = 1).
      One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and
      68.2% (95% CI, 44.6% to 83.4%) with 31 months median follow-up. This is the first
      RIC protocol demonstrating durable UCB engraftment in children with NMD. Future
      risk-based modifications of this regimen could decrease the incidence of viral
      infections. (www.clinicaltrials.gov/NCT00744692).

PMID- 24296494
TI  - Increasing incidence of pyogenic spondylodiscitis: a 14-year population-based
      study.
AB  - OBJECTIVES: Smaller studies indicate that the incidence of pyogenic
      spondylodiscitis is increasing, possible related to a growing elderly population.
      Data supporting this is sparse, and we therefore studied patient characteristics
      and changes in spondylodiscitis incidence 1995-2008. METHODS: In a population
      based study we identified all patients aged >=18 years treated for pyogenic
      spondylodiscitis in Funen County, Denmark (population 483 123). Annual incidences
      were determined. Demographics, symptoms and diagnostic methods were recorded.
      RESULTS: We found 192 cases: median age 66.6 years; 57.3% men; 76.6% culture
      positive cases. Staphylococcus aureus was the most common pathogen (55.1%).
      During 1995-2008 the overall incidence, incidence of culture negative cases, and
      incidence of cases due to S. aureus increased 2.2-5.8, 0.3-1.8, and 1.6-2.5 cases
      per 100 000 person years, respectively. The elderly had the highest incidence
      compared to those aged <=70 years (rate ratio for men 5.9 (95% CI: 4.2-8.5) and
      for women 3.5 (95% CI: 2.3-5.3)). CONCLUSIONS: During 1995-2008 the overall
      incidence of S. aureus and culture negative cases of spondylodiscitis increased
      and remained highest among the elderly. Whether the increase is real or is a
      result of improved diagnostic methods and workup remains unknown.

PMID- 24296495
TI  - Development and bias assessment of a method for targeted metagenomic sequencing
      of marine cyanobacteria.
AB  - Prochlorococcus and Synechococcus are the most abundant photosynthetic organisms
      in oligotrophic waters and responsible for a significant percentage of the
      earth's primary production. Here we developed a method for metagenomic sequencing
      of sorted Prochlorococcus and Synechococcus populations using a transposon-based
      library preparation technique. First, we observed that the cell lysis technique
      and associated amount of input DNA had an important role in determining the DNA
      library quality. Second, we found that our transposon-based method provided a
      more even coverage distribution and matched more sequences of a reference genome
      than multiple displacement amplification, a commonly used method for metagenomic
      sequencing. We then demonstrated the method on Prochlorococcus and Synechococcus
      field populations from the Sargasso Sea and California Current isolated by flow
      cytometric sorting and found clear environmentally related differences in ecotype
      distributions and gene abundances. In addition, we saw a significant
      correspondence between metagenomic libraries sequenced with our technique and
      regular sequencing of bulk DNA. Our results show that this targeted method is a
      viable replacement for regular metagenomic approaches and will be useful for
      identifying the biogeography and genome content of specific marine cyanobacterial
      populations. 

PMID- 24296496
TI  - Use of limited proteolysis and mutagenesis to identify folding domains and
      sequence motifs critical for wax ester synthase/acyl coenzyme A:diacylglycerol
      acyltransferase activity.
AB  - Triacylglycerols and wax esters are synthesized as energy storage molecules by
      some proteobacteria and actinobacteria under stress. The enzyme responsible for
      neutral lipid accumulation is the bifunctional wax ester synthase/acyl-coenzyme A
      (CoA):diacylglycerol acyltransferase (WS/DGAT). Structural modeling of WS/DGAT
      suggests that it can adopt an acyl-CoA-dependent acyltransferase fold with the N
      terminal and C-terminal domains connected by a helical linker, an architecture
      demonstrated experimentally by limited proteolysis. Moreover, we found that both
      domains form an active complex when coexpressed as independent polypeptides. The
      structural prediction and sequence alignment of different WS/DGAT proteins
      indicated catalytically important motifs in the enzyme. Their role was probed by
      measuring the activities of a series of alanine scanning mutants. Our study
      underscores the structural understanding of this protein family and paves the way
      for their modification to improve the production of neutral lipids. 

PMID- 24296498
TI  - Motility characteristics are altered for Rickettsia bellii transformed to
      overexpress a heterologous rickA gene.
AB  - The rickettsial protein RickA activates host cell factors associated with the
      eukaryotic actin cytoskeleton and is likely involved with rickettsial host cell
      binding and infection and the actin-based motility of spotted fever group
      rickettsiae. The rickA gene sequence and protein vary substantially between
      Rickettsia species, as do observed motility-associated phenotypes. To help
      elucidate the function of RickA and determine the effects of species-specific
      RickA variations, we compared extracellular binding, intracellular motility, and
      intercellular spread phenotypes of three Rickettsia bellii variants. These
      included two shuttle vector-transformed R. bellii strains and the wild-type
      isolate from which they were derived, R. bellii RML 369C. Both plasmid shuttle
      vectors carried spectinomycin resistance and a GFPuv reporter; one contained
      Rickettsia monacensis-derived rickA, and the other lacked the rickA gene.
      Rickettsia bellii transformed to express R. monacensis rickA highly overexpressed
      this transcript in comparison to its native rickA. These rickettsiae also moved
      at higher velocities and followed a more curved path than the negative-control
      transformants. A lower proportion of R. monacensis rickA-expressing bacteria ever
      became motile, however, and they formed smaller plaques. 

PMID- 24296497
TI  - An oleaginous bacterium that intrinsically accumulates long-chain free Fatty
      acids in its cytoplasm.
AB  - Medium- and long-chain fatty acids are present in organisms in esterified forms
      that serve as cell membrane constituents and storage compounds. A large number of
      organisms are known to accumulate lipophilic materials as a source of energy and
      carbon. We found a bacterium, designated GK12, that intrinsically accumulates
      free fatty acids (FFAs) as intracellular droplets without exhibiting
      cytotoxicity. GK12 is an obligatory anaerobic, mesophilic lactic acid bacterium
      that was isolated from a methanogenic reactor. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that GK12 is affiliated with the family
      Erysipelotrichaceae in the phylum Firmicutes but is distantly related to type
      species in this family (less than 92% similarity in 16S rRNA gene sequence).
      Saturated fatty acids with carbon chain lengths of 14, 16, 18, and 20 were
      produced from glucose under stress conditions, including higher-than-optimum
      temperatures and the presence of organic solvents that affect cell membrane
      integrity. FFAs were produced at levels corresponding to up to 25% (wt/wt) of the
      dry cell mass. Our data suggest that FFA accumulation is a result of an imbalance
      between excess membrane fatty acid biosynthesis due to homeoviscous adaptation
      and limited beta-oxidation activity due to anaerobic growth involving lactic acid
      fermentation. FFA droplets were not further utilized as an energy and carbon
      source, even under conditions of starvation. A naturally occurring bacterium that
      accumulates significant amounts of long-chain FFAs with noncytotoxicity would
      provide useful strategies for microbial biodiesel production. 

PMID- 24296499
TI  - Intersubspecific recombination in Xylella fastidiosa Strains native to the United
      States: infection of novel hosts associated with an unsuccessful invasion.
AB  - The bacterial pathogen Xylella fastidiosa infects xylem and causes disease in
      many plant species in the Americas. Different subspecies of this bacterium and
      different genotypes within subspecies infect different plant hosts, but the
      genetics of host adaptation are unknown. Here we examined the hypothesis that the
      introduction of novel genetic variation via intersubspecific homologous
      recombination (IHR) facilitates host shifts. We investigated IHR in 33 X.
      fastidiosa subsp. multiplex isolates previously identified as recombinant based
      on 8 loci (7 multilocus sequence typing [MLST] loci plus 1 locus). We found
      significant evidence of introgression from X. fastidiosa subsp. fastidiosa in 4
      of the loci and, using published data, evidence of IHR in 6 of 9 additional loci.
      Our data showed that IHR regions in 2 of the 4 loci were inconsistent (12
      mismatches) with X. fastidiosa subsp. fastidiosa alleles found in the United
      States but consistent with alleles from Central America. The other two loci were
      consistent with alleles from both regions. We propose that the recombinant forms
      all originated via genomewide recombination of one X. fastidiosa subsp. multiplex
      ancestor with one X. fastidiosa subsp. fastidiosa donor from Central America that
      was introduced into the United States but subsequently disappeared. Using all of
      the available data, 5 plant hosts of the recombinant types were identified, 3 of
      which also supported non-IHR X. fastidiosa subsp. multiplex, but 2 were unique to
      recombinant types from blueberry (7 isolates from Georgia, 3 from Florida); and
      blackberry (1 each from Florida and North Carolina), strongly supporting the
      hypothesis that IHR facilitated a host shift to blueberry and possibly
      blackberry. 

PMID- 24296500
TI  - Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained
      stable during a 6-month randomized controlled diet intervention with the new
      nordic diet.
AB  - It has been suggested that the human gut microbiota can be divided into
      enterotypes based on the abundance of specific bacterial groups; however, the
      biological significance and stability of these enterotypes remain unresolved.
      Here, we demonstrated that subjects (n = 62) 18 to 65 years old with central
      obesity and components of metabolic syndrome could be grouped into two discrete
      groups simply by their relative abundance of Prevotella spp. divided by
      Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Furthermore,
      we showed that these groups remained stable during a 6-month, controlled dietary
      intervention, where the effect of consuming a diet in accord with the new Nordic
      diet (NND) recommendations as opposed to consuming the average Danish diet (ADD)
      on the gut microbiota was investigated. In this study, subjects (with and without
      stratification according to P/B ratio) did not reveal significant changes in 35
      selected bacterial taxa quantified by quantitative PCR (ADD compared to NND)
      resulting from the dietary interventions. However, we found higher total plasma
      cholesterol within the high-P/B group than in the low-P/B group after the
      intervention. We propose that stratification of humans based simply on their P/B
      ratio could allow better assessment of possible effects of interventions on the
      gut microbiota and physiological biomarkers. 

PMID- 24296501
TI  - Novel maltotriose-hydrolyzing thermoacidophilic type III pullulan hydrolase from
      Thermococcus kodakarensis.
AB  - A novel thermoacidophilic pullulan-hydrolyzing enzyme (PUL) from
      hyperthermophilic archaeon Thermococcus kodakarensis (TK-PUL) that efficiently
      hydrolyzes starch under industrial conditions in the absence of any additional
      metal ions was cloned and characterized. TK-PUL possessed both pullulanase and
      alpha-amylase activities. The highest activities were observed at 95 to 100
      degrees C. Although the enzyme was active over a broad pH range (3.0 to 8.5), the
      pH optima for both activities were 3.5 in acetate buffer and 4.2 in citrate
      buffer. TK-PUL was stable for several hours at 90 degrees C. Its half-life at 100
      degrees C was 45 min when incubated either at pH 6.5 or 8.5. The Km value toward
      pullulan was 2 mg ml(-1), with a Vmax of 109 U mg(-1). Metal ions were not
      required for the activity and stability of recombinant TK-PUL. The enzyme was
      able to hydrolyze both alpha-1,6 and alpha-1,4 glycosidic linkages in pullulan.
      The most preferred substrate, after pullulan, was gamma-cyclodextrin, which is a
      novel feature for this type of enzyme. Additionally, the enzyme hydrolyzed a
      variety of polysaccharides, including starch, glycogen, dextrin, amylose,
      amylopectin, and cyclodextrins (alpha, beta, and gamma), mainly into maltose. A
      unique feature of TK-PUL was the ability to hydrolyze maltotriose into maltose
      and glucose. 

PMID- 24296502
TI  - Ingestibility, digestibility, and engineered biological control potential of
      Flavobacterium hibernum, isolated from larval mosquito habitats.
AB  - Flavobacterium hibernum, isolated from larval habitats of the eastern tree hole
      mosquito, A. triseriatus, remained suspended in the larval feeding zone much
      longer (8 days) than other bacteria. Autofluorescent protein markers were
      developed for the labeling of F. hibernum with a strong flavobacterial expression
      system. Green fluorescent protein (GFP)-tagged F. hibernum cells were quickly
      consumed by larval mosquitoes at an ingestion rate of 9.5 * 10(4)/larva/h. The
      ingested F. hibernum cells were observed mostly in the foregut and midgut and
      rarely in the hindgut, suggesting that cells were digested and did not pass the
      gut viably. The NanoLuc luciferase reporter system was validated for quantitative
      larval ingestion rate and bacterial fate analyses. Larvae digested 1.87 * 10(5)
      cells/larva/h, and few F. hibernum cells were excreted intact. Expression of the
      GFP::Cry11A fusion protein with the P20 chaperone protein from Bacillus
      thuringiensis H-14 was successfully achieved in F. hibernum. Whole-cell bioassays
      of recombinant F. hibernum exhibited high larvicidal activity against A.
      triseriatus in microplates and in microcosms simulating tree holes. F. hibernum
      cells persisted in microcosms at 100, 59, 30, and 10% of the initial densities at
      days 1, 2, 3, and 6, respectively, when larvae were absent, while larvae consumed
      nearly all of the F. hibernum cells within 3 days of their addition to
      microcosms. 

PMID- 24296503
TI  - Intimin gene (eae) subtype-based real-time PCR strategy for specific detection of
      Shiga toxin-producing Escherichia coli serotypes O157:H7, O26:H11, O103:H2,
      O111:H8, and O145:H28 in cattle feces.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains belonging to serotypes
      O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28 are known to be associated with
      particular subtypes of the intimin gene (eae), namely, gamma1, beta1, epsilon,
      theta, and gamma1, respectively. This study aimed at evaluating the usefulness of
      their detection for the specific detection of these five main pathogenic STEC
      serotypes in cattle feces. Using real-time PCR assays, 58.7% of 150 fecal samples
      were found positive for at least one of the four targeted eae subtypes. The
      simultaneous presence of stx, eae, and one of the five O group markers was found
      in 58.0% of the samples, and the five targeted stx plus eae plus O genetic
      combinations were detected 143 times. However, taking into consideration the
      association between eae subtypes and O group markers, the resulting stx plus eae
      subtype plus O combinations were detected only 46 times. The 46 isolation assays
      performed allowed recovery of 22 E. coli strains belonging to one of the five
      targeted STEC serogroups. In contrast, only 2 of 39 isolation assays performed on
      samples that were positive for stx, eae and an O group marker, but that were
      negative for the corresponding eae subtype, were successful. Characterization of
      the 24 E. coli isolates showed that 6 were STEC, including 1 O157:H7, 3 O26:H11,
      and 2 O145:H28. The remaining 18 strains corresponded to atypical
      enteropathogenic E. coli (aEPEC). Finally, the more discriminating eae subtype
      based PCR strategy described here may be helpful for the specific screening of
      the five major STEC in cattle feces. 

PMID- 24296504
TI  - Insertion sequence element single nucleotide polymorphism typing provides
      insights into the population structure and evolution of Mycobacterium ulcerans
      across Africa.
AB  - Buruli ulcer is an indolent, slowly progressing necrotizing disease of the skin
      caused by infection with Mycobacterium ulcerans. In the present study, we applied
      a redesigned technique to a vast panel of M. ulcerans disease isolates and
      clinical samples originating from multiple African disease foci in order to (i)
      gain fundamental insights into the population structure and evolutionary history
      of the pathogen and (ii) disentangle the phylogeographic relationships within the
      genetically conserved cluster of African M. ulcerans. Our analyses identified 23
      different African insertion sequence element single nucleotide polymorphism (ISE
      SNP) types that dominate in different areas where Buruli ulcer is endemic. These
      ISE-SNP types appear to be the initial stages of clonal diversification from a
      common, possibly ancestral ISE-SNP type. ISE-SNP types were found unevenly
      distributed over the greater West African hydrological drainage basins. Our
      findings suggest that geographical barriers bordering the basins to some extent
      prevented bacterial gene flow between basins and that this resulted in
      independent focal transmission clusters associated with the hydrological drainage
      areas. Different phylogenetic methods yielded two well-supported sister clades
      within the African ISE-SNP types. The ISE-SNP types from the "pan-African clade"
      were found to be widespread throughout Africa, while the ISE-SNP types of the
      "Gabonese/Cameroonian clade" were much rarer and found in a more restricted area,
      which suggested that the latter clade evolved more recently. Additionally, the
      Gabonese/Cameroonian clade was found to form a strongly supported monophyletic
      group with Papua New Guinean ISE-SNP type 8, which is unrelated to other
      Southeast Asian ISE-SNP types. 

PMID- 24296505
TI  - An unbiased method for clustering bacterial effectors using host cellular
      phenotypes.
AB  - We present a novel method implementing unbiased high-content morphometric cell
      analysis to classify bacterial effector phenotypes. This clustering methodology
      represents a significant advance over more qualitative visual approaches and can
      also be used to classify, and therefore predict the likely function of, unknown
      effector genes from any microbial genome. As a proof of concept, we use this
      approach to investigate 23 genetic regions predicted to encode antimacrophage
      effectors located across the genome of the insect and human pathogen Photorhabdus
      asymbiotica. Statistical cluster analysis using multiple cellular measures
      categorized treated macrophage phenotypes into three major groups relating to
      their putative functionality: (i) adhesins, (ii) cytolethal toxins, and (iii)
      cytomodulating toxins. Further investigation into their effects on phagocytosis
      revealed that several effectors also modulate this function and that the nature
      of this modulation (increased or decreased phagocytosis) is linked to the
      phenotype cluster group. Categorizing potential functionalities in this way
      allows rapid functional follow-up of key candidates for more-directed cell
      biological or biochemical investigation. Such an unbiased approach to the
      classification of candidate effectors will be useful for describing virulence
      related regions in a wide range of genomes and will be useful in assigning
      putative functions to the growing number of microbial genes whose function
      remains unclear from homology searching. 

PMID- 24296506
TI  - A Geobacter sulfurreducens strain expressing pseudomonas aeruginosa type IV pili
      localizes OmcS on pili but is deficient in Fe(III) oxide reduction and current
      production.
AB  - The conductive pili of Geobacter species play an important role in electron
      transfer to Fe(III) oxides, in long-range electron transport through current
      producing biofilms, and in direct interspecies electron transfer. Although
      multiple lines of evidence have indicated that the pili of Geobacter
      sulfurreducens have a metal-like conductivity, independent of the presence of c
      type cytochromes, this claim is still controversial. In order to further
      investigate this phenomenon, a strain of G. sulfurreducens, designated strain PA,
      was constructed in which the gene for the native PilA, the structural pilin
      protein, was replaced with the PilA gene of Pseudomonas aeruginosa PAO1. Strain
      PA expressed and properly assembled P. aeruginosa PilA subunits into pili and
      exhibited a profile of outer surface c-type cytochromes similar to that of a
      control strain expressing the G. sulfurreducens PilA. Surprisingly, the strain PA
      pili were decorated with the c-type cytochrome OmcS in a manner similar to the
      control strain. However, the strain PA pili were 14-fold less conductive than the
      pili of the control strain, and strain PA was severely impaired in Fe(III) oxide
      reduction and current production. These results demonstrate that the presence of
      OmcS on pili is not sufficient to confer conductivity to pili and suggest that
      there are unique structural features of the G. sulfurreducens PilA that are
      necessary for conductivity. 

PMID- 24296508
TI  - Electromechanical properties of 1D ZnO nanostructures: nanopiezotronics building
      blocks, surface and size-scale effects.
AB  - One-dimensional (1D) zinc oxide nanostructures are the main components of
      nanogenerators and central to the emerging field of nanopiezotronics.
      Understanding the underlying physics and quantifying the electromechanical
      properties of these structures, the topic of this research study, play a major
      role in designing next-generation nanoelectromechanical devices. Here, atomistic
      simulations are utilized to study surface and size-scale effects on the
      electromechanical response of 1D ZnO nanostructures. It is shown that the
      mechanical and piezoelectric properties of these structures are controlled by
      their size, cross-sectional geometry, and loading configuration. The study
      reveals enhancement of the piezoelectric and elastic modulus of ZnO nanowires
      (NW) with diameter d > 1 nm, followed by a sudden drop for d < 1 nm due to
      transformation of NWs to nanotubes (NTs). Degradation of mechanical and
      piezoelectric properties of ZnO nanobelts (NBs) followed by an enhancement in
      piezoelectric properties occurs when their lower dimension is reduced to <1 nm.
      The latter enhancement can be explained in the context of surface reconfiguration
      and formation of hexagon-tetragon (HT) pairs at the intersection of (21[combining
      macron]1[combining macron]0) and (011[combining macron]0) planes in NBs.
      Transition from a surface-reconstructed dominant to a surface-relaxed dominant
      region is demonstrated for lateral dimensions <1 nm. New phase-transformation
      (PT) kinetics from piezoelectric wurtzite to nonpiezoelectric body-centered
      tetragonal (WZ -> BCT) and graphite-like phase (WZ -> HX) structures occurs in
      ZnO NWs loaded up to large strains of ~10%. 

PMID- 24296507
TI  - Novel Firmicutes group implicated in the dechlorination of two chlorinated
      xanthones, analogues of natural organochlorines.
AB  - Although the abundance and diversity of natural organochlorines are well
      established, much is still unknown about the degradation of these compounds.
      Triplicate microcosms were used to determine whether, and which, bacterial
      communities could dechlorinate two chlorinated xanthones (2,7-dichloroxanthone
      and 5,7-dichloro-1,3-dihydroxylxanthone), analogues of a diverse class of natural
      organochlorines. According to quantitative-PCR (qPCR) results, several known
      dechlorinating genera were either not present or not enriched during
      dechlorination of the xanthones. Denaturing gradient gel electrophoresis,
      however, indicated that several Firmicutes were enriched in the dechlorinating
      cultures compared to triplicate controls amended with nonchlorinated xanthones.
      One such group, herein referred to as the Gopher group, was further studied with
      a novel qPCR method that confirmed enrichment of Gopher group 16S rRNA genes in
      the dechlorinating cultures. The enrichment of the Gopher group was again tested
      with two new sets of triplicate microcosms. Enrichment was observed during
      chlorinated xanthone dechlorination in one set of these triplicate microcosms. In
      the other set, two microcosms showed clear enrichment while a third did not. The
      Gopher group is a previously unidentified group of Firmicutes, distinct from but
      related to the Dehalobacter and Desulfitobacterium genera; this group also
      contains clones from at least four unique cultures capable of dechlorinating
      anthropogenic organochlorines that have been previously described in the
      literature. This study suggests that natural chlorinated xanthones may be
      effective biostimulants to enhance the remediation of pollutants and highlights
      the idea that novel genera of dechlorinators likely exist and may be active in
      bioremediation and the natural cycling of chlorine. 

PMID- 24296509
TI  - Dendrimer-like polymeric DNAs as chemiluminescence probes for amplified detection
      of telomere DNA on a solid-phase membrane.
AB  - For the first time, an amplified chemiluminescence (CL) detection of the telomere
      DNA spotted on a nylon membrane is described here, based on the direct
      hybridization with the CL probe of dendrimer-like polymeric DNAs possessing a
      large number of guanine moieties. This probe was synthesized by sense and
      antisense hybridization between Y-shaped DNAs and then could hybridize with the
      target DNA. 

PMID- 24296510
TI  - Structural modulation of silver complexes and their distinctive catalytic
      properties.
AB  - A family of silver(I) complexes, [Ag2(L)2(OOCCF3)2] (1), [Ag(L)0.5(OOCCF3)] (2),
      [Ag(L)2](OOCCF3)(H2O)2 (3), was obtained by reactions of 4,4'-di(2
      oxazolinyl)biphenyl (L) and AgOOCCF3 in different reaction media. Compound 1 has
      a 1D chain structure with alternative connections between the Ag(I) and L ligand.
      When the crystal nucleation inductor, pyrazine, was added into the reaction
      system, complex 2 was isolated with no pyrazine observed in its structure. In 2,
      the 1D inorganic chains formed by Ag(I) cations and OOCCF3(-) anions were
      connected by the L ligand to produce a 2D network. When a different inductor,
      imidazole, was added into the reaction system, 3 with (4,4) topology was
      synthesized, and again no imidazole was found in 3. When 1-3 were used as
      catalysts for cycloaddition reactions between imino esters and methyl acrylate, 3
      affords the highest yield, in which the particular size of the channels in 3 led
      to its selective catalytic performance.

PMID- 24296511
TI  - RNAi-derived field resistance to Cassava brown streak disease persists across the
      vegetative cropping cycle.
AB  - A confined field trial was established to determine durability of RNAi-mediated
      resistance to Cassava brown streak disease (CBSD). Stem cuttings were obtained
      from field-grown cassava plants of cv 60444 transgenic for construct p718,
      consisting of an 894 bp inverted repeat sequence from the Ugandan Cassava brown
      streak virus (UCBSV) coat protein. Plants were established from three transgenic
      lines previously shown to provide complete resistance to UCBSV and differing
      levels of protection to the non-homologous virus species Cassava brown streak
      virus (CBSV), and grown for 11 months. CBSD symptoms were observed on shoots and
      storage roots of all non-transgenic cv 60444 control plants and transgenic lines
      p718-002 and p718-005, but not on p718-001. RT-PCR diagnostic showed tissues of
      plant lines p718-002 and p718-005 to be infected with CBSV, but free of UCBSV.
      All leaves and roots of p718-001 plants were to carry no detectable levels of
      either pathogen. Plants of cv 60444 in this field trial showed severe cassava
      mosaic disease symptoms, indicating that presence of replicating geminiviruses
      did not cause significant suppression of RNAi-mediated resistance to CBSD.
      Resistance to CBSD across a vegetative cropping cycle confirms earlier field
      data, and provides an important step in proof of concept for application of RNAi
      technology to control of CBSD under conditions encountered in farmers' fields. 

PMID- 24296512
TI  - Detection of chronic obstructive pulmonary disease in primary care in Salzburg,
      Austria: findings from the real world.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health
      burden and profoundly affects individuals suffering from the disease. However,
      the majority of subjects with COPD are still undiagnosed. OBJECTIVES: To evaluate
      COPD prevalence and detection strategies for COPD in the primary-care setting.
      METHODS: The study was conducted in a random sample of general practitioner (GP)
      offices in Salzburg (Austria). A questionnaire and post-bronchodilator (PBD)
      spirometry was administered to patients aged >= 40 years. Nonreversible airway
      obstruction was considered when PBD FEV1/FVC was <0.70. Severity of
      spirometrically defined COPD was graded according to the GOLD recommendations.
      RESULTS: 60 GP offices were randomly selected for study participation, however
      only 30 (50.0%) were willing to participate. 1,230 of 9,820 (12.52%) patients
      consented to the protocol. Quality of PBD spirometry was evaluated, and 882
      (71.7%) met ATS/ERS quality criteria. 7.5% (95% CI: 5.7-9.4%) of the patients had
      COPD grade II+ (FEV1/FVC <0.7 and FEV1 <80% of predicted), but only 22.4% of them
      reported a prior physician's diagnosis of COPD. Similar results were seen for the
      2005 Salzburg BOLD (Burden of Obstructive Lung Disease) sample with regard to
      COPD GOLD II+ prevalence (10.7%) and proportion of underdiagnosis (82.3%).
      CONCLUSION: COPD in the primary-care setting is as prevalent and underdiagnosed
      as reported recently for the BOLD study. The surprisingly low participation rate
      of GPs and patients indicates that prevention of COPD is not a health priority,
      and that awareness for COPD has to heightened before case-finding strategies will
      be successful.

PMID- 24296513
TI  - Formation of supported rhodium clusters from mononuclear rhodium complexes
      controlled by the support and ligands on rhodium.
AB  - Extremely small supported rhodium clusters were prepared from rhodium complexes
      on the surfaces of solids with contrasting electron-donor properties. The samples
      were characterized by infrared and extended X-ray absorption fine structure
      spectroscopies to determine the changes occurring in the rhodium species
      resulting from treatments in hydrogen. Rhodium cluster formation occurred in the
      presence of H2, and the first steps are controlled by the electron-donor
      properties of the support--which acts as a ligand--and the other ligands bonded
      to the rhodium. The cluster formation begins at a lower temperature when the
      support is zeolite HY than when it is the better electron-donor MgO, provided
      that the other ligands on rhodium are ethene. In contrast, when these other
      ligands are CO, the pattern is reversed. The choice of ligands including the
      support also allows regulation of the stoichiometry of the surface
      transformations in H2 and the stability of the structures formed in the presence
      of other reactants. The combination of MgO as the support and ethene as a ligand
      allows restriction of the rhodium cluster size to the smallest possible-and these
      were formed in high yields. The data presented here are among the first
      characterizing the first steps of metal cluster formation.

PMID- 24296514
TI  - Remembering Bernard Becker, MD, 1920-2013.

PMID- 24296516
TI  - Thyroid cancer in 2013: Advances in our understanding of differentiated thyroid
      cancer.
AB  - Studies published in 2013 have addressed the question of whether the rising
      incidence of differentiated thyroid cancer is actually the result of
      overdiagnosis. Advances have also been made in the treatment of differentiated
      thyroid cancer, including improvements in radioiodine therapy.

PMID- 24296515
TI  - A heart-adipose tissue connection in the regulation of energy metabolism.
AB  - Almost 20 years ago, the protein encoded by the ob locus in mice was identified
      as an adipocyte-secreted hormone, now termed leptin, which functions as a
      peripheral signal to communicate the organism's energy reserve--and thereby
      protects against starvation due to insufficient caloric resources. Additional
      peripheral factors have since been identified that coordinate interorgan
      crosstalk to manage energy resources. The heart is included in this network
      through its regulated release of natriuretic peptides A and B--cardiac hormones
      originally identified as important in blood pressure control. Emerging evidence
      that natriuretic peptide receptors are expressed in adipose tissue, and that
      circulating levels of these peptides are decreased in animals and humans with
      obesity, could imply that natriuretic peptides are also involved in the
      regulation of energy metabolism. The natriuretic peptides stimulate triglyceride
      lipolysis in adipocytes, a process also regulated by the sympathetic nervous
      system. In addition, these two pathways promote uncoupling of mitochondrial
      respiration and thermogenesis in brown adipocytes. This Review focuses on the
      roles of the natriuretic peptides and the sympathetic nervous system in
      regulating adipocyte metabolism. The potential for manipulating the natriuretic
      peptide pathway to increase energy expenditure in obesity and manage the
      complications of cardiometabolic disease is also discussed.

PMID- 24296517
TI  - The effects of two different doses of calcium lactate on blood pH, bicarbonate,
      and repeated high-intensity exercise performance.
AB  - We investigated the effects of low- and high-dose calcium lactate supplementation
      on blood pH and bicarbonate (Study A) and on repeated high-intensity performance
      (Study B). In Study A, 10 young, physically active men (age: 24 +/- 2.5 years;
      weight: 79.2 +/- 9.45 kg; height: 1.79 +/- 0.06 m) were assigned to acutely
      receive three different treatments, in a crossover fashion: high-dose calcium
      lactate (HD: 300 mg . kg(-1) body mass), low-dose calcium lactate (LD: 150 mg .
      kg(-1) body mass) and placebo (PL). During each visit, participants received one
      of these treatments and were assessed for blood pH and bicarbonate 0, 60, 90,
      120, 150, 180, and 240 min following ingestion. In Study B, 12 young male
      participants (age: 26 +/- 4.5 years; weight: 82.0 +/- 11.0 kg; height: 1.81 +/-
      0.07 m) received the same treatments of Study A. Ninety minutes after ingestion,
      participants underwent 3 bouts of the upper-body Wingate test and were assessed
      for blood pH and bicarbonate 0 and 90 min following ingestion and immediately
      after exercise. In Study A, both HD and LD promoted slight but significant
      increases in blood bicarbonate (31.47 +/- 1.57 and 31.69 +/- 1.04 mmol . L(-1,
      respectively) and pH levels (7.36 +/- 0.02 and 7.36 +/- 0.01, respectively), with
      no effect of PL. In Study B, total work done, peak power, mean power output were
      not affected by treatments. In conclusion, low- and high-dose calcium lactate
      supplementation induced similar, yet very discrete, increases in blood pH and
      bicarbonate, which were not sufficiently large to improve repeated high-intensity
      performance.

PMID- 24296518
TI  - Identification of risk factors for new-onset sciatica in Japanese workers:
      findings from the Japan epidemiological research of Occupation-related Back pain
      study.
AB  - STUDY DESIGN: Two-year, prospective cohort data collected for the Japan
      epidemiological research of Occupation-related Back pain study were used for the
      analysis. OBJECTIVE: To identify potential risk factors for the development of
      new-onset sciatica in initially symptom-free Japanese workers with no history of
      sciatica. SUMMARY OF BACKGROUND DATA: Although the associations between
      individual and occupational factors and cases of new-onset sciatica are
      established, the effect of psychosocial factors on the development of sciatica
      has still not been adequately clarified. METHODS: In total, 5310 participants
      responded to a self-administered baseline questionnaire (response rate: 86.5%).
      Furthermore, 3194 (60.2%) completed both 1- and 2-year follow-up questionnaires.
      The baseline questionnaire assessed individual characteristics, ergonomic work
      demands, and work-related psychosocial factors. The outcome of interest was new
      onset sciatica with or without low back pain during the 2-year follow-up period.
      Incidence was calculated for participants who reported no low back pain in the
      preceding year and no history of lumbar radicular pain (sciatica) at baseline.
      Logistical regression assessed risk factors associated with new-onset sciatica.
      RESULTS: Of 765 eligible participants, 141 (18.4%) reported a new episode of
      sciatica during the 2-year follow-up. In crude analysis, significant associations
      were found between new-onset sciatica and age and obesity. In adjusted analysis,
      significant associations were found for obesity and mental workload in a
      qualitative aspect after controlling for age and sex. Consequently, in
      multivariate analysis with all the potential risk factors, age and obesity
      remained statistically significant (odds ratios: 1.59, 95% confidence interval:
      1.01-2.52; odds ratios: 1.77, 95% confidence interval: 1.17-2.68, respectively).
      CONCLUSION: In previously asymptomatic Japanese workers, the risk of developing
      new-onset sciatica is mediated by individual factors. Our findings suggest that
      the management of obesity may prevent new-onset sciatica. LEVEL OF EVIDENCE: 3.

PMID- 24296519
TI  - The role of prostaglandin and antioxidant availability in recovery from forearm
      ischemia-reperfusion injury in humans.
AB  - BACKGROUND: Endothelial dysfunction, manifesting as attenuated flow-mediated
      dilation (FMD), is clinically important. Antioxidants may prevent this
      dysfunction; however, the acute effects of oral administration in humans are
      unknown. Low flow-mediated constriction (L-FMC), a further parameter of
      endothelial health, is largely unstudied and the mechanisms for this response
      unclear. METHODS: Twelve healthy participants (five women and seven men)
      completed three test conditions: control; antioxidant cocktail (alpha-lipoic
      acid, vitamins C and E); and prostaglandin inhibitor ingestion (ibuprofen).
      Ultrasound measurements of brachial artery responses were assessed throughout 5
      min of forearm ischemia and 3 min after. Subsequently, an ischemia-reperfusion
      injury was induced by a 20-min upper arm occlusion. Further, vascular function
      protocols were completed at 15, 30, and 45 min of recovery. RESULTS: Endothelial
      dysfunction was evident in all conditions. FMD was attenuated at 15 min after
      ischemia-reperfusion injury (Pre: 6.24 +/- 0.58%; Post15: 0.24 +/- 0.75%; mean +/
      SD, P < 0.05), but recovered by 45 min. Antioxidant administration did not
      preserve FMD compared with control (P > 0.05). The magnitude of L-FMC was
      augmented at 15 min (Pre: 1.44 +/- 0.27%; Post15: 3.75 +/- 1.73%; P < 0.05) and
      recovered by 45 min. Ibuprofen administration produced the largest constrictive
      response (Pre: -1.13 +/- 1.71%; Post15: -5.57 +/- 3.82%; time * condition
      interaction: P < 0.05). CONCLUSION: Results demonstrate ischemia-reperfusion
      injury causes endothelial dysfunction and acute oral antioxidant supplementation
      fails to reduce its magnitude. Our results also suggest that a lack of shear
      stress during occlusion combined with suppression of prostaglandin synthesis
      magnifies L-FMC, possibly due to augmented endothelin-1 expression.

PMID- 24296520
TI  - Molecular and metabolic consequences following E6 transfection in an isogenic
      ovarian cell line (A2780) pair.
AB  - AIMS: To examine molecular and metabolic consequences of HPV-16 viral- protein
      E6, which targets p53 for degradation, in A2780 (ovarian cancer) cells. METHODS:
      Isogenic derivatives of A2780 cells, with empty-vector (E6-) or E6 (E6+)
      transfection, were cultured. Intracellular metabolites, fatty acids, and the flux
      of glutamine, glucose, alanine and lactate in proliferation (Day 2) and
      confluence (Day 4) were determined using MRS. Western blotting confirmed p53
      status, protein expressions related to AKT, ERK and mTOR signalling, and
      phospholipid metabolism. RESULTS: Growth rate was slower in E6+ cells compared
      with E6-, resulting in reduced glycolysis, amino acid uptake and fatty acid
      synthesis. Glutamine metabolism, glycerophosphocholine (GPC), and protein
      expressions of cytosolic PLA2 (cPLA2) and p-cPLA2 increased in E6+ cells. Despite
      decreased ERK and AKT signalling, expression of S6RP and p-S6RP downstream of
      mTOR remained unaffected in E6+ cells. E6+ cells were more invasive and migrate
      faster than the E6- cells. CONCLUSION: E6+ had slower growth than E6- cells with
      reduced metabolism, but E6+ cells maintained cellular homeostasis through
      glutamine metabolism when compared with E6- at Day 2. The ability to migrate and
      form larger colonies may provide the E6+ cells with a growth advantage.

PMID- 24296521
TI  - A proposal for a novel impact factor as an alternative to the JCR impact factor.
AB  - One disadvantage of the JCR impact factor, the most commonly used assessment tool
      for ranking and evaluating scientific journals, is its inability in
      distinguishing among different shapes of citation distribution curves, leading to
      unfair evaluation of journals in some cases. This paper aims to put forward an
      alternative impact factor (IF') that can properly reflect citation distributions.
      The two impact factors are linearly and positively correlated, and have roughly
      the same order of magnitude. Because of the ability of IF' in distinguishing
      among different shapes of citation distribution curves, IF' may properly reflect
      the academic performance of a scientific journal in a way that is different from
      the JCR impact factor with some unique features that reward journals with highly
      cited papers. Therefore, it is suggested that IF' could be used to complement the
      JCR impact factor. 

PMID- 24296522
TI  - Vocal characteristics during child development: perceptual-auditory and acoustic
      data.
AB  - OBJECTIVE: To analyze perceptual-auditory and acoustic characteristics of
      children's voices of different age ranges. PATIENTS AND METHODS: Ninety-three 3-
      to 10-year-old children grouped from 3 to 5, 6 to 7, and 8 to 10 years served as
      participants. The severity of vocal deviation and the parameters of roughness,
      breathiness, strain, and instability were assessed using a visual analog scale.
      We calculated the mean and standard deviation of fundamental frequency (F0),
      jitter, shimmer, and glottal-to-noise excitation ratio for the sustained vowel,
      and the mean of F0 variability for connected speech. RESULTS: The most affected
      voices were in the age range 8-10 years, and only the phonation tension level was
      reduced as a result of aging. There were significant differences between children
      aged 3-5 years and the other age ranges for F0 mean for sustained vowels and F0
      variability. CONCLUSION: Children aged 8-10 years had the highest severity of
      vocal deviation. There was a significant reduction of phonation tension and
      measure of F0, jitter, and shimmer after the age of 5 years.

PMID- 24296523
TI  - Large unstained cells: a potentially valuable parameter in the assessment of
      immune activation levels in HIV infection.
AB  - INTRODUCTION: Chronic immune activation is associated with the accelerated
      progression of HIV to AIDS; however, affordable markers reflecting this have not
      yet been determined. The percentage of large unstained cells (%LUCs) is a
      differential count parameter measured by certain routine hematology analyzers and
      reflects activated lymphocytes and peroxidase-negative cells. We hypothesized
      that the %LUCs would be increased in HIV infection and would correlate with
      markers of immune activation [i.e. CD38 expression on CD8+ T cells (%CD38onCD8)
      and lipopolysaccharide-binding protein (LBP)] and CD4 counts. METHODS: In this
      cross-sectional study, 78 HIV-infected, antiretroviral therapy-naive adults and
      52 uninfected controls were recruited. %CD38onCD8 and CD4 counts were determined
      by flow cytometry, LBP levels were assessed by immunoassay, and the %LUCs was
      tested on a Siemens ADVIA 2120. RESULTS: Significant differences were found
      between the HIV-infected and control groups for %LUCs (95% CI 2.3-2.7 vs. 1.8
      2.2, respectively; p = 0.001), as well as for %CD38onCD8, LBP, and CD4 counts.
      Furthermore, %LUCs correlated directly with %CD38onCD8 and LBP and inversely with
      CD4 counts. CONCLUSION: The %LUCs was significantly increased in this untreated,
      asymptomatic, HIV-infected group and correlated with markers of immune activation
      and CD4 counts. Therefore, the %LUCs may be of value in identifying HIV-infected
      patients at risk of accelerated disease progression.

PMID- 24296525
TI  - Density functional theory analysis of structural and electronic properties of
      orthorhombic perovskite CH3NH3PbI3.
AB  - The organic-inorganic hybrid perovskite CH3NH3PbI3 is a novel light harvester,
      which can greatly improve the solar-conversion efficiency of dye-sensitized solar
      cells. In this article, a first-principle theoretical study is performed using
      local, semi-local and non-local exchange-correlation approximations to find a
      suitable method for this material. Our results, using the non-local optB86b +
      vdWDF functional, excellently agree with the experimental data. Thus,
      consideration of weak van der Waals interactions is demonstrated to be important
      for the accurate description of the properties of this type of organic-inorganic
      hybrid materials. Further analysis of the electronic properties reveals that I 5p
      electrons can be photo-excited to Pb 6p empty states. The main interaction
      between the organic cations and the inorganic framework is through the ionic
      bonding between CH3 and I ions. Furthermore, I atoms in the Pb-I framework are
      found to be chemically inequivalent because of their different chemical
      environments. 

PMID- 24296524
TI  - Karyological characterization of the endemic Iberian rock lizard, Iberolacerta
      monticola (Squamata, Lacertidae): insights into sex chromosome evolution.
AB  - Rock lizards of the genus Iberolacerta constitute a promising model to examine
      the process of sex chromosome evolution, as these closely related taxa exhibit
      remarkable diversity in the degree of sex chromosome differentiation with no
      clear phylogenetic segregation, ranging from cryptic to highly heteromorphic ZW
      chromosomes and even multiple chromosome systems (Z1Z1Z2Z2/Z1Z2W). To gain a
      deeper insight into the patterns of karyotype and sex chromosome evolution, we
      performed a cytogenetic analysis based on conventional staining, banding
      techniques and fluorescence in situ hybridization in the species I. monticola,
      for which previous cytogenetic investigations did not detect differentiated sex
      chromosomes. The karyotype is composed of 2n = 36 acrocentric chromosomes. NORs
      and the major ribosomal genes were located in the subtelomeric region of
      chromosome pair 6. Hybridization signals of the telomeric sequences (TTAGGG)n
      were visualized at the telomeres of all chromosomes and interstitially in 5
      chromosome pairs. C-banding showed constitutive heterochromatin at the
      centromeres of all chromosomes, as well as clear pericentromeric and light
      telomeric C-bands in several chromosome pairs. These results highlight some
      chromosomal markers which can be useful to identify species-specific diagnostic
      characters, although they may not accurately reflect the phylogenetic
      relationships among the taxa. In addition, C-banding revealed the presence of a
      heteromorphic ZW sex chromosome pair, where W is smaller than Z and almost
      completely heterochromatic. This finding sheds light on sex chromosome evolution
      in the genus Iberolacerta and suggests that further comparative cytogenetic
      analyses are needed to understand the processes underlying the origin,
      differentiation and plasticity of sex chromosome systems in lacertid lizards.

PMID- 24296526
TI  - Oxygen mediated synthesis of high quality InN nanowires above their decomposition
      temperature.
AB  - A novel method for synthesis of high quality InN nanowires, at temperatures well
      above their decomposition temperature, has been demonstrated by utilizing
      controlled oxygen flow in the growth chamber. Detailed structural and chemical
      analyses indicate that the nanowires consist of pure InN, with no evidence of
      In2O3 detected by any of the characterization methods. It is proposed that the
      oxygen, pre-adsorbed on the Au catalyst surface, assists in accelerating the
      decomposition of NH3 at the growth temperature by providing high concentration of
      atomic nitrogen to assist in the growth, and prevent decomposition of the InN
      nanowires, without getting incorporated in them. The proposed role of oxygen is
      supported by improved material quality at higher oxygen flow rates. 

PMID- 24296527
TI  - Living ring-opening homo- and copolymerisation of epsilon-caprolactone and L
      lactide by cyclic beta-ketiminato aluminium complexes.
AB  - A series of novel aluminium complexes containing cyclic beta-ketiminato ligands
      of type Me2Al{O-[(ArN=CHC4H4(C6H4))]} (3a, Ar = 2,6-(i)Pr2C6H3; 3b, Ar = C6H5;
      3c, Ar = C6F5) have been prepared in high yields. These complexes were identified
      by (1)H, (13)C NMR spectroscopy and elemental analysis. X-ray structural analyses
      for 3a-c revealed that these complexes have a distorted tetrahedral geometry
      around Al, and both bond distances and bond angles were considerably influenced
      by the ligand structure. These complexes were tested as catalyst precursors for
      ring-opening polymerisation of epsilon-caprolactone (epsilon-CL) and L-lactide (L
      LA) in the presence of 2-propanol as an initiator. Complex 3a could polymerize
      epsilon-CL in a controlled manner with high efficiency. Based on the living
      characteristics, the preparation of well-defined block copolymers PCL-b-PLLA via
      sequential addition of monomers was performed by 3a. Note that complex 3c
      exhibited rather high catalytic activity for the ROP of L-LA with narrow
      molecular weight distribution. The monomer conversion reached completion only in
      4 h when the L-LA/Al molar ratio was 100 at 80  degrees C. PLLA-b-PCL copolymers
      were thus easily produced by 3c.

PMID- 24296528
TI  - Effect of continuous positive airway pressure treatment for obstructive sleep
      apnoea on visual processing of degraded words.
AB  - BACKGROUND: In a previous uncontrolled study, continuous positive airway pressure
      (CPAP) therapy for obstructive sleep apnoea (OSA) improved vision in patients
      with diabetic macular oedema. OBJECTIVES: We investigated whether the above
      improvement in vision (or visual processing) might have been due to reduced
      sleepiness, rather than a true improvement in retinal function. METHODS: Twelve
      normal control subjects and 20 patients with OSA were tested for their ability to
      recognise degraded words, by means of a computer programme displaying 5-letter
      words every 4 s for 10 min, with variable amounts of the bottom half of the word
      missing; the percentage of the word necessary to achieve correct identification
      on average half the time was 'hunted' (the test score). All subjects were tested
      twice, 2-3 weeks apart; the OSA group after the commencement of CPAP. The Epworth
      Sleepiness Score (ESS) in patients was measured at the same visit. RESULTS: The
      test score at visit 1 was 26.7% for normal subjects and 31.6% for patients with
      OSA. At visit 2, the test score was 25.0% for normal subjects and 29.9% for
      patients with OSA. The groups showed a small and identical improvement over the
      trial period in the test score, of 1.7% (p = 0.01 and p = 0.03 for the normal and
      OSA groups, respectively). The group with OSA experienced a drop in ESS of 7.5
      (SD 5.5) points following treatment. CONCLUSION: The small and identical
      improvement in both groups suggests only a similar learning effect rather than
      any improvement due to reduced sleepiness.

PMID- 24296529
TI  - Effect of 1O2 quencher depletion on the efficiency of photodynamic therapy.
AB  - Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) fluorescence and
      photodynamic oxygen consumption were monitored during AlPcS4-photodynamic therapy
      (PDT) of Mat LyLu cells in suspension. These measurements were used to calculate
      the PDT efficiency, which is defined as the oxygen consumption rate divided by
      the sensitizer concentration. As a function of the intracellular oxygen
      concentration consumed by PDT, the normalized PDT efficiency fell off more
      quickly at lower photosensitizer concentrations. The changes in PDT efficiency
      were compared to models of PDT in which the photosensitizer (PS) and singlet
      oxygen quencher (A) were either free to diffuse or were fixed. The model in which
      PS and A are free to diffuse did not agree with the experimental data because
      this model predicts that the reduction in PDT efficiency is independent of [PS].
      A Monte Carlo model was written to simulate PDT when both PS and A are
      stationary. This model was found to describe the experimental data when the
      initial intracellular [A] = 90 mM and when the initial and final (i.e. after all
      A has been depleted) singlet oxygen lifetimes were 0.4 and 1.2 MUs respectively.

PMID- 24296531
TI  - Tetrel bond-sigma-hole bond as a preliminary stage of the SN2 reaction.
AB  - MP2/aug-cc-pVTZ calculations were carried out on complexes of ZH4, ZFH3 and ZF4
      (Z = C, Si and Ge) molecules with HCN, LiCN and Cl(-) species acting as Lewis
      bases through nitrogen centre or chlorine ion. Z-Atoms in these complexes usually
      act as Lewis acid centres forming sigma-hole bonds with Lewis bases. Such
      noncovalent interactions may adopt a name of tetrel bonds since they concern the
      elements of the group IV. There are exceptions for complexes of CH4 and CF4, as
      well as for the F4SiNCH complex where the tetrel bond is not formed. The
      energetic and geometrical parameters of the complexes were analyzed and numerous
      correlations between them were found. The Quantum Theory of 'Atoms in Molecules'
      and Natural Bonds Orbital (NBO) method used here should deepen the understanding
      of the nature of the tetrel bond. An analysis of the electrostatic potential
      surfaces of the interacting species is performed. The electron charge
      redistribution, being the result of the tetrel bond formation, is the same as
      that of the SN2 reaction. The energetic and geometrical parameters of the
      complexes analyzed here correspond to different stages of the SN2 process. 

PMID- 24296532
TI  - Viral evolution: Flu host evasion.

PMID- 24296533
TI  - Epistasis and quantitative traits: using model organisms to study gene-gene
      interactions.
AB  - The role of epistasis in the genetic architecture of quantitative traits is
      controversial, despite the biological plausibility that nonlinear molecular
      interactions underpin the genotype-phenotype map. This controversy arises because
      most genetic variation for quantitative traits is additive. However, additive
      variance is consistent with pervasive epistasis. In this Review, I discuss
      experimental designs to detect the contribution of epistasis to quantitative
      trait phenotypes in model organisms. These studies indicate that epistasis is
      common, and that additivity can be an emergent property of underlying genetic
      interaction networks. Epistasis causes hidden quantitative genetic variation in
      natural populations and could be responsible for the small additive effects,
      missing heritability and the lack of replication that are typically observed for
      human complex traits. 

PMID- 24296536
TI  - Evolution: Transposons drive sex chromosome evolution.

PMID- 24296534
TI  - Systems genetics approaches to understand complex traits.
AB  - Systems genetics is an approach to understand the flow of biological information
      that underlies complex traits. It uses a range of experimental and statistical
      methods to quantitate and integrate intermediate phenotypes, such as transcript,
      protein or metabolite levels, in populations that vary for traits of interest.
      Systems genetics studies have provided the first global view of the molecular
      architecture of complex traits and are useful for the identification of genes,
      pathways and networks that underlie common human diseases. Given the urgent need
      to understand how the thousands of loci that have been identified in genome-wide
      association studies contribute to disease susceptibility, systems genetics is
      likely to become an increasingly important approach to understanding both biology
      and disease. 

PMID- 24296535
TI  - Long non-coding RNAs: new players in cell differentiation and development.
AB  - Genomes of multicellular organisms are characterized by the pervasive expression
      of different types of non-coding RNAs (ncRNAs). Long ncRNAs (lncRNAs) belong to a
      novel heterogeneous class of ncRNAs that includes thousands of different species.
      lncRNAs have crucial roles in gene expression control during both developmental
      and differentiation processes, and the number of lncRNA species increases in
      genomes of developmentally complex organisms, which highlights the importance of
      RNA-based levels of control in the evolution of multicellular organisms. In this
      Review, we describe the function of lncRNAs in developmental processes, such as
      in dosage compensation, genomic imprinting, cell differentiation and
      organogenesis, with a particular emphasis on mammalian development. 

PMID- 24296538
TI  - Impact of anesthesia on mortality during endovascular clot removal for acute
      ischemic stroke.
AB  - BACKGROUND: Endovascular clot retrieval is a technique available for removing
      intracranial arterial occlusions in acute ischemic stroke (AIS). This rescue
      therapy can be performed with moderate conscious sedation (CS) or general
      anesthesia (GA). The effect of GA on clinical outcome in AIS remains
      controversial. Therefore, we retrospectively investigated whether the use of CS
      or GA during endovascular intervention for AIS influenced outcomes. METHODS:
      Patients who underwent emergent endovascular intervention for intracranial
      arterial occlusion during the years 2006 to 2012 were included in this study.
      Statistical analysis using the Spearman rho was performed to examine demographic
      data and clinical outcomes between patients in the GA and CS groups. Binary
      logistic regression was used to determine the predictors of mortality. RESULTS: A
      total of 109 patients fit the inclusion criteria. Among them, 35 patients had GA
      and 74 patients had CS. Patients needing intubation upon admission for airway
      protection were more likely to receive GA (P<0.001). The duration of the
      procedure and the time-to-revascularization from symptom onset were significantly
      longer in the GA group. Mortality was higher in the GA group compared with the CS
      group (40% vs. 22%, P=0.045). Multivariate analysis, controlled for confounding
      variables, identified GA and elevated postprocedure glucose level to be
      significant predictors of mortality. CONCLUSIONS: Larger prospectively randomized
      multicenter trials evaluating the effects of GA and CS on clinical and
      radiographic outcomes seems warranted.

PMID- 24296537
TI  - Critical role of SCD1 in autophagy regulation via lipogenesis and lipid rafts
      coupled AKT-FOXO1 signaling pathway.
AB  - SCD1 (stearoyl-coenzyme A desaturase 1) is an endoplasmic reticulum-bound enzyme
      that catalyzes the formation of the first double bond at the cis-Delta9 position
      of saturated fatty acids (SFA) to form monounsaturated fatty acids (MUFA).
      Increasing evidence indicates that autophagy plays an important role in
      regulating lipid metabolism, while little is known about whether key enzymes of
      lipogenesis like SCD1 can regulate autophagy. In this study, we examined the role
      of SCD1 in autophagy using the tsc2(-/-) mouse embryonic fibroblasts (MEFs)
      possessing constitutively active MTORC1 as a cellular model. We found that mRNA
      and protein levels of SCD1 are significantly elevated in the tsc2(-/-) MEFs
      compared with Tsc2(+/+) MEFs, resulting in significant increases in levels of
      various lipid classes. Furthermore, inhibition of SCD1 activity by either a
      chemical inhibitor or genetic knockdown resulted in an increase of autophagic
      flux only in the tsc2(-/-) MEFs. Induction of autophagy was independent of MTOR
      as MTORC1 activity was not suppressed by SCD1 inhibition. Loss of phosphorylation
      on AKT Ser473 was observed upon SCD1 inhibition and such AKT inactivation was due
      to disruption of lipid raft formation, without affecting the formation and
      activity of MTORC2. Increased nuclear translocation of FOXO1 was observed
      following AKT inactivation, leading to increased transcription of genes involved
      in the autophagic process. The tsc2(-/-) MEFs were also more susceptible to
      apoptosis induced by SCD1 inhibition and blockage of autophagy sensitized the
      cell death response. These results revealed a novel function of SCD1 on
      regulation of autophagy via lipogenesis and the lipid rafts-AKT-FOXO1 pathway. 

PMID- 24296539
TI  - Factors that correlate with the decision to delay extubation after multilevel
      prone spine surgery.
AB  - BACKGROUND: Multilevel spinal decompressions and fusions often require long
      anesthetic and operative times, which may result in airway edema and prolonged
      postoperative intubation. Delayed extubation can lead to bronchopulmonary
      infections and other complications. This study analyzed which factors correlated
      with the decision to delay extubation after multilevel spine surgery. METHODS: We
      reviewed the records of 289 patients who underwent multilevel spine surgery
      lasting >=8 hours in the prone position from 2006 to 2012. Variables hypothesized
      to affect the decision of the anesthesiologist to delay extubation at the end of
      the surgery were collected. These included preoperative factors (age, sex, ASA
      class, history of obstructive sleep apnea, BMI, previous spine surgery, current
      cervical surgery, anterior in addition to posterior spine surgery, emergency
      surgery) and intraoperative factors (difficult intubation, number of surgical
      levels, case time, estimated blood loss, fluid and blood administration,
      attending handoff and resident handoff, and case end time). We also compared the
      incidence of pulmonary postoperative complications between patients extubated at
      the end of the case to patients who had a delayed extubation. RESULTS: A total of
      126 patients (44%) were kept intubated after multilevel spine surgery. Multiple
      linear regression analysis showed factors that correlated with prolonged
      intubation which included age, ASA class, procedure duration, extent of surgery,
      total crystalloid volume administered, total blood volume administered, and the
      case end time. Patients who had a delayed extubation had a 3-fold higher rate of
      postoperative pneumonia. CONCLUSIONS: Our study found that age, ASA class,
      procedure duration, extent of surgery, and total crystalloid and blood volume
      administered correlate with the decision to delay extubation in multilevel prone
      spine surgery. It also finds that the time the case ends is an independent
      variable that correlates with the decision not to extubate at the end of a long
      multilevel spinal surgery. The incidence of postoperative pneumonia is higher in
      patients who had a delayed extubation after surgery.

PMID- 24296540
TI  - Anesthetic management of neurosurgical procedures during pregnancy: a case
      series.
AB  - INTRODUCTION: Neurosurgical disorders are rare during pregnancy and challenge the
      anesthesiologist with conflicting anesthetic considerations and little evidence
      to guide decision-making. Our objective was to review the anesthetic management
      of pregnant patients undergoing intracranial neurosurgery at our institution and
      to describe the perioperative complications and outcomes. METHODS: We used our
      institutional Discharge Abstract Database to identify patients assigned both
      neurological and obstetrical International Classification of Disease 10-A codes
      between April 1, 2001 and March 1, 2012. Pregnant patients who underwent
      intracranial neurosurgical procedures underwent a detailed chart review to
      extract demographic data and details about their anesthetic management and
      outcome. RESULTS: Nine patients underwent full chart review with a median age of
      28 (range, 17 to 35) years and a gestational age of 23 (range, 7 to 30) weeks.
      Patients underwent a craniotomy for vascular lesions (4), neoplasms (3), and
      traumatic brain injuries (2). One patient was hyperventilated (PaCO2 28 mmHg),
      and mannitol and furosemide were used in 6 and 3 patients, respectively, without
      complication. Maternal neurological outcomes were good in 5 patients (Glasgow
      Outcome Scale of >3), poor in 3 patients (Glasgow Outcome Scale 3), and 1 patient
      died. Fetal outcomes were good in 5 patients and poor in 4 patients (1
      therapeutic abortion, 3 intrauterine fetal demises). All cases of fetal distress
      or demise were either remote or occurred before the anesthetic management.
      CONCLUSIONS: Pregnant patients undergoing neurosurgery experience a high rate of
      morbidity and mortality. There were no adverse outcomes directly attributed to
      the use of osmotic diuretics and hyperventilation in our series.

PMID- 24296541
TI  - Favorable outcome after a subdural hematoma treated with feiba in a 77-year-old
      patient treated by rivaroxaban.

PMID- 24296542
TI  - Prospective flutemetamol positron emission tomography and histopathology in
      normal pressure hydrocephalus.
AB  - BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the
      amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and
      the level of amyloid-beta measured by immunohistochemical and histochemical
      staining in a frontal cortical region biopsy site. METHODS: Seventeen patients
      with probable normal pressure hydrocephalus (NPH) underwent prospective
      [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during
      ventriculoperitoneal shunting. Tissue amyloid-beta was evaluated using the
      monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. RESULTS:
      Four of the 17 patients (23.5%) had amyloid-beta pathology based on the overall
      pathology read and also showed increased [(18)F]flutemetamol uptake.
      [(18)F]Flutemetamol standardized uptake values from the biopsy site were
      significantly associated with biopsy specimen amyloid-beta levels (Pearson's r =
      0.67; p = 0.006). There was also good correlation between the biopsy specimen
      amyloid-beta level and uptake of [(18)F]flutemetamol in the region contralateral
      to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical
      [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed
      a high level of agreement between all readers (kappa = 0.88). Two of 3 readers
      were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH
      cases. Blinded visual assessments of PET images by 1 reader were associated with
      100% sensitivity to the overall pathology read, and assessments by the 2 others
      were associated with 75% sensitivity (overall sensitivity by majority read was
      75%); specificity of all readers was 100%. CONCLUSIONS: [(18)F]Flutemetamol
      detects brain amyloid-beta in vivo and shows promise as a valuable tool to study
      and possibly facilitate diagnosis of Alzheimer's disease both in patients with
      suspected NPH and among the wider population.

PMID- 24296543
TI  - Acoustic-perceptual relationships in variants of clear speech.
AB  - OBJECTIVE: The acoustic basis of intelligibility associated with varied clear
      speech instructions was studied. METHODS: Twelve healthy speakers read 18
      sentences in 'habitual', 'clear', 'hearing impaired' and 'overenunciate'
      conditions. The latter 3 conditions are varieties of clear speech. Acoustic
      measures included tense and lax vowel space area, a measure of vowel spectral
      change, articulation rate and sentence-level vocal intensity. Sentences were
      mixed with multitalker babble to prevent ceiling effects and were
      orthographically transcribed by 40 listeners. Percent-correct scores were
      obtained for each speaker and condition. Regression analyses were used to
      quantify relationships between acoustic measures and intelligibility. RESULTS:
      Univariate regressions indicated that greater magnitudes of acoustic change in
      nonhabitual conditions were associated with greater increases in intelligibility.
      Multivariate regression analysis further indicated that lax vowel space,
      articulation rate and vocal intensity were significant predictors of
      intelligibility. CONCLUSIONS: Acoustic variables associated with intelligibility
      differed depending on whether relationships were examined using univariate or
      multivariate statistics. Multivariate statistics indicated that articulation rate
      was the strongest predictor of improvements in intelligibility above and beyond
      all other variables studied. The findings have implications for optimizing
      therapeutic use of clear speech for clinical populations.

PMID- 24296544
TI  - F8 genetic analysis strategies when standard approaches fail.
AB  - Haemophilia A is a common X-linked recessive disorder caused by mutations in F8
      leading to deficiency or dysfunction of coagulant factor VIII (FVIII). Despite
      tremendous improvements in mutation screening methods, in a small group of
      patients with FVIII deficiency suffering from haemophilia A, no DNA change can be
      found. In these patients, analysis reveals no causal mutations even after
      sequencing the whole coding region of F8 including the flanking splice sites, as
      well as the promoter and the 3' untranslated region (UTR). After excluding the
      mutations mimicking the haemophilia A phenotype in interacting partners of the
      FVIII protein affecting the half life and transport of the protein, mutations or
      rearrangements in non-coding regions of F8 have to be considered responsible for
      the haemophilia A phenotype. In this review, we present the experiences with
      molecular diagnosis of such cases and approaches to be applied for mutation
      negative patients. 

PMID- 24296545
TI  - C-C bond migration in the cycloisomerization of oxygen-tethered 1,6-enynes.
AB  - A C-C bond migration event during the cycloisomerization of 1,6-enynes is
      described. Two different catalytic systems, iridium- or platinum-based, are able
      to induce this process. Alkyl migrations of larger rings and acyclic groups
      indicate that the reaction is not fully driven by the release of ring strain. 

PMID- 24296546
TI  - Endoscopic ulnar nerve release and transposition.
AB  - The most common site of ulnar nerve compression is within the cubital tunnel.
      Surgery has historically involved an open cubital tunnel release with or without
      transposition of the nerve. A comparative study has demonstrated that endoscopic
      decompression is as effective as open decompression and has the advantages of
      being less invasive, utilizing a smaller incision, producing less local symptoms,
      causing less vascular insult to the nerve, and resulting in faster recovery for
      the patient. Ulnar nerve transposition is indicated with symptomatic ulnar nerve
      instability or if the ulnar nerve is located in a "hostile bed" (eg, osteophytes,
      scarring, ganglions, etc.). Transposition has previously been performed as an
      open procedure. The authors describe a technique of endoscopic ulnar nerve
      release and transposition. Extra portals are used to allow retractors to be
      inserted, the medial intermuscular septum to be excised, cautery to be used, and
      a tape to control the position of the nerve. In our experience this minimally
      invasive technique provides good early outcomes. This report details the
      indications, contraindications, surgical technique, and rehabilitation of the
      endoscopic ulnar nerve release and transposition. 

PMID- 24296547
TI  - Activation of chloride secretion by isoflavone genistein in endometrial
      epithelial cells.
AB  - BACKGROUND/AIM: Genistein, the most active isoflavone found primarily in
      soybeans, alters ion transport functions in intestinal and airway epithelia. The
      present study aims to investigate the acute effects and mechanisms of action of
      genistein in immortalized porcine endometrial epithelial cells. METHODS: Ussing
      chamber technique was used for transepithelial electrical measurements. RESULTS:
      Genistein increased short-circuit currents (Isc) which were inhibited by
      glibenclamide, NPPB, CFTRinh-172, DIDS or bumetanide, but not amiloride. In
      experiments with amphotericin B-permeabilized monolayers, genistein activated the
      apical Cl- current and barium-sensitive basolateral K+ current while inhibiting
      the apical K+ current. Genistein failed to increase the Isc in the presence of
      forskolin or IBMX, but did increase the Isc in UTP. Pretreatment with genistein
      also abolished the increase in the Isc when induced by forskolin, IBMX or UTP.
      However, Ca2+-chelating BAPTA-AM did not affect the genistein-induced increase in
      the Isc. The genistein-stimulated Isc was reduced by tyrosine kinase inhibitors,
      tyrphostin A23 or AG490. However, vanadate, a tyrosine phosphatase inhibitor,
      failed to inhibit the genistein response. Estrogen receptor antagonist ICI182,780
      did not alter the genistein's action. CONCLUSION: The soy isoflavone, genistein,
      stimulates Cl- secretion in endometrial epithelial cells possibly via a direct
      activation of CFTR which appears to be modulated through a tyrosine kinase
      dependent pathway. The present findings may be of benefit for the therapeutic
      application of genistein in the treatment of electrolyte transport disorders in
      the epithelia.

PMID- 24296548
TI  - One-step synthesis and shape-control of CuPd nanowire networks.
AB  - An effective one-step method has been developed to synthesize CuPd bimetallic
      nanowire networks. Investigation of the growth process revealed that the
      nanowires were formed by attachment of spherical particles and strongly
      influenced by interactions between surface ligands and metals. The morphology of
      CuPd nanoparticles is tuned via changing the molecular weight of
      polyvinylpyrrolidone (PVP) and solvents. The versatility of this method was
      further demonstrated by preparation of AgPd nanowires. An electrochemical study
      of CuPd nanowire networks shows morphology dependent activity in oxygen reduction
      reaction (ORR), which is comparable to that of platinum. 

PMID- 24296549
TI  - A combined experimental and computational study of fluxional processes in sigma
      amine-borane complexes of rhodium and iridium.
AB  - A combined experimental and computational study on the fluxional processes
      involving the M-H and B-H positions in the sigma amine-borane complexes
      [M(PR3)2(H)2(eta(2)-H3B.NMe3)][BAr(F)4] (M = Rh, Ir; R = Cy for experiment; R =
      Me, Cy for computation; Ar(F) = 3,5-(CF3)2C6H3) is reported. The processes
      studied are: B-H bridging/terminal exchange; reaction with exogenous D2 leading
      to exchange at M-H; and intramolecular M-H/B-H exchange. Experimentally it was
      found that B-H bridging/terminal exchange is most accessible and slightly
      favoured for Rh; D2/M-H exchange occurs at qualitatively similar rates for both M
      = Rh and Ir, while M-H/B-H exchange is the slowest overall, with the Ir congener
      having a lower barrier than Rh. Evidence for the isotopic perturbation of
      equilibrium is also reported for the BH/BD isotopologues of [Ir(PCy3)2(H)2(eta(2)
      H3B.NMe3)][BAr(F)4]. DFT calculations using model complexes (R = Me)
      qualitatively reproduce the relative rates of the various exchange processes for
      both M = Rh and Ir, i.e. barriers for B-H bridging/terminal exchange are less
      than those for M-H/H2 exchange, which in turn are less than those for M-H/B-H
      exchange. Which metal promotes these processes more effectively depends upon the
      nature of the rate-limiting transition state, which can change between Rh and Ir.
      Computational analysis of the full experimental system (R = Cy) reveals similar
      overall trends in terms of the relative ease of the various exchange processes.
      However, there are differences in the details, and these are discussed. 

PMID- 24296550
TI  - Homology versus convergence in resolving transphyletic correspondences of brain
      organization.
AB  - Due to the largely absent fossil record, phylogenetic comparisons of brain
      structures rely on the analysis of nervous systems in extant taxa, many of which
      appear to have distinctive and dissimilar neural arrangements. The use of a
      multitude of comparative criteria, including developmental genetics,
      phylogenomics and neural circuit architecture, has recently resolved a highly
      conserved structural and functional ground pattern organization in the arthropod
      central complex and vertebrate basal ganglia. The minuteness of resemblance is
      exemplified by orthologous action selection circuits that are formed by
      homologous gene networks and which can lead to similar pathologies and behavioral
      disorders. It has been argued, however, that these similarities of brain centers
      can only be due to convergent evolution. What is still missing is a plausible
      scenario to explain how convergence could result in such a multitude of
      similarities and minuteness of resemblances, including gene expression,
      functional attributes and pathologies. In contrast, homology by common descent is
      the more parsimonious explanation. Moreover, the divergent elaboration of
      arthropod central complex and vertebrate basal ganglia does not obscure their
      shared ground pattern organization and thus genealogical correspondence.

PMID- 24296551
TI  - A primer on the synthesis, water-solubilization, and functionalization of quantum
      dots, their use as biological sensing agents, and present status.
AB  - The use of nanomaterials, specifically fluorescent semiconductor quantum dots
      (QDs), for biological imaging and sensing has become very topical. Here we
      present a historical synopsis of research in this field to help elucidate the
      origins of the most recent advances in QD-based technology. We further aim to
      educate the novice researcher concerning many important aspects of QD synthesis,
      water-solubilization, functionalization, and usage in biological imaging and
      sensing that are generally not discussed in the literature. We will also
      summarize several recent transformative examples of using quantum dots for in
      vitro and in vivo studies. 

PMID- 24296552
TI  - Acquired von Willebrand syndrome with a type 2B phenotype: diagnostic and
      therapeutic dilemmas.
AB  - In this report, we provide evidence of an acquired von Willebrand syndrome (AVWS)
      with a type 2B phenotype rather than the expected type 1 or 2A. The patient was
      referred prior to surgical removal of a fibrous mass within the maxillary sinus.
      His first bleeding 7 years earlier following a retinal tear had been complicated
      by monocular blindness. Several mucocutanous bleedings followed. Hematological
      investigations revealed von Willebrand factor (VWF):Ag 91 IU/ml, factor VIII 86
      IU/ml, VWF:RCo 34 IU/ml and profound thrombocytopenia with platelet clumping. VWF
      multimer analysis showed a loss of high-molecular-weight multimers and his plasma
      aggregated normal platelets under low ristocetin concentration, consistent with
      type 2B von Willebrand disease (VWD). Sequencing of VWF exon 28 and of the
      platelet GP1BA gene to investigate the possibility of platelet-type VWD failed to
      reveal mutations. Serum protein electrophoresis showed a monoclonal IgG protein
      and led to the diagnosis of monoclonal gammopathy of unknown significance (MGUS),
      raising suspicion of an AVWS. Over 2 years, he experienced severe gingival
      bleedings and traumatic intracerebral hemorrhage. Following debridement of the
      sinus mass, the patient required 20 units of packed red blood cells, despite high
      dose Humate-P, continuous Amicar and twice-daily platelet transfusions. Bleeding
      finally ceased following infusion of activated factor VIIa. A history of prior
      uncomplicated vasectomy and tendon laceration, no family history of bleeding, the
      inability to identify a causative mutation in either exon 28 VWF or platelet
      GP1BA and the MGUS led to diagnosis of AVWS with a type 2B phenotype. This case
      highlights the difficulties in assigning a diagnosis and the management of
      bleeding in a patient with an atypical presentation of AVWS.

PMID- 24296567
TI  - Automated fall detection with quality improvement "rewind" to reduce falls in
      hospital rooms.
AB  - The purpose of this study was to test the implementation of a fall detection and
      "rewind" privacy-protecting technique using the Microsoft(r) KinectTM to not only
      detect but prevent falls from occurring in hospitalized patients. Kinect sensors
      were placed in six hospital rooms in a step-down unit and data were continuously
      logged. Prior to implementation with patients, three researchers performed a
      total of 18 falls (walking and then falling down or falling from the bed) and 17
      non-fall events (crouching down, stooping down to tie shoe laces, and lying on
      the floor). All falls and non-falls were correctly identified using automated
      algorithms to process Kinect sensor data. During the first 8 months of data
      collection, processing methods were perfected to manage data and provide a
      "rewind" method to view events that led to falls for post-fall quality
      improvement process analyses. Preliminary data from this feasibility study show
      that using the Microsoft Kinect sensors provides detection of falls, fall risks,
      and facilitates quality improvement after falls in real hospital environments
      unobtrusively, while taking into account patient privacy.

PMID- 24296568
TI  - What's stopping a career in gerontological nursing?: literature review.
AB  - Despite the rapid aging of the world's population, many countries are
      experiencing difficulty in recruiting nurses to work with older people. A
      literature review was conducted regarding the career preferences of undergraduate
      nursing students from seven different countries. The literature review has
      identified that gerontological nursing does not feature highly as a career goal.
      Notably, this has been the situation for the past decade. There is no indication
      that the situation is going to change at any time in the future unless some
      serious decisions are made at professional, health service, community, and
      government levels. This literature review has identified the reasons why
      undergraduate nurses are not choosing gerontological nursing as a career, what
      has been done in an attempt to address the problem, and what else may be done.

PMID- 24296569
TI  - Carbon nanofiber mesoporous films: efficient platforms for bio-hydrogen oxidation
      in biofuel cells.
AB  - The discovery of oxygen and carbon monoxide tolerant [NiFe] hydrogenases was the
      first necessary step toward the definition of a novel generation of hydrogen fed
      biofuel cells. The next important milestone is now to identify and overcome
      bottlenecks limiting the current densities, hence the power densities. In the
      present work we report for the first time a comprehensive study of herringbone
      carbon nanofiber mesoporous films as platforms for enhanced biooxidation of
      hydrogen. The 3D network allows mediatorless hydrogen oxidation by the membrane
      bound hydrogenase from the hyperthermophilic bacterium Aquifex aeolicus. We
      investigate the key physico-chemical parameters that enhance the catalytic
      efficiency, including surface chemistry and hierarchical porosity of the
      biohybrid film. We also emphasize that the catalytic current is limited by mass
      transport inside the mesoporous carbon nanofiber film. Provided hydrogen is
      supplied inside the carbon film, the combination of the hierarchical porosity of
      the carbon nanofiber film with the hydrophobicity of the treated carbon material
      results in very high efficiency of the bioelectrode. By optimization of the whole
      procedure, current densities as high as 4.5 mA cm(-2) are reached with a turnover
      frequency of 48 s(-1). This current density is almost 100 times higher than when
      hydrogenase is simply adsorbed at a bare graphite electrode, and more than 5
      times higher than the average of the previous reported current densities at
      carbon nanotube modified electrodes, suggesting that carbon nanofibers can be
      efficiently used in future sustainable H2/O2 biofuel cells. 

PMID- 24296570
TI  - The singular quest for a universal tree of life.
AB  - Carl Woese developed a unique research program, based on rRNA, for discerning
      bacterial relationships and constructing a universal tree of life. Woese's
      interest in the evolution of the genetic code led to him to investigate the deep
      roots of evolution, develop the concept of the progenote, and conceive of the
      Archaea. In so doing, he and his colleagues at the University of Illinois in
      Urbana revolutionized microbiology and brought the classification of microbes
      into an evolutionary framework. Woese also provided definitive evidence for the
      role of symbiosis in the evolution of the eukaryotic cell while underscoring the
      importance of lateral gene transfer in microbial evolution. Woese and colleagues'
      proposal of three fundamental domains of life was brought forward in direct
      conflict with the prokaryote-eukaryote dichotomy. Together with several
      colleagues and associates, he brought together diverse evidence to support the
      rRNA evidence for the fundamentally tripartite nature of life. This paper aims to
      provide insight into his accomplishments, how he achieved them, and his place in
      the history of biology. 

PMID- 24296571
TI  - Mx proteins: antiviral gatekeepers that restrain the uninvited.
AB  - Fifty years after the discovery of the mouse Mx1 gene, researchers are still
      trying to understand the molecular details of the antiviral mechanisms mediated
      by Mx proteins. Mx proteins are evolutionarily conserved dynamin-like large
      GTPases, and GTPase activity is required for their antiviral activity. The
      expression of Mx genes is controlled by type I and type III interferons. A
      phylogenetic analysis revealed that Mx genes are present in almost all
      vertebrates, usually in one to three copies. Mx proteins are best known for
      inhibiting negative-stranded RNA viruses, but they also inhibit other virus
      families. Recent structural analyses provide hints about the antiviral mechanisms
      of Mx proteins, but it is not known how they can suppress such a wide variety of
      viruses lacking an obvious common molecular pattern. Perhaps they interact with a
      (partially) symmetrical invading oligomeric structure, such as a viral
      ribonucleoprotein complex. Such an interaction may be of a fairly low affinity,
      in line with the broad target specificity of Mx proteins, yet it would be strong
      enough to instigate Mx oligomerization and ring assembly. Such a model is
      compatible with the broad "substrate" specificity of Mx proteins: depending on
      the size of the invading viral ribonucleoprotein complexes that need to be
      wrapped, the assembly process would consume the necessary amount of Mx precursor
      molecules. These Mx ring structures might then act as energy-consuming wrenches
      to disassemble the viral target structure.

PMID- 24296572
TI  - Variations in virulence and molecular biology among emerging strains of
      Clostridium difficile.
AB  - Clostridium difficile is a Gram-positive, spore-forming organism which infects
      and colonizes the large intestine, produces potent toxins, triggers inflammation,
      and causes significant systemic complications. Treating C. difficile infection
      (CDI) has always been difficult, because the disease is both caused and resolved
      by antibiotic treatment. For three and a half decades, C. difficile has presented
      a treatment challenge to clinicians, and the situation took a turn for the worse
      about 10 years ago. An increase in epidemic outbreaks related to CDI was first
      noticed around 2003, and these outbreaks correlated with a sudden increase in the
      mortality rate of this illness. Further studies discovered that these changes in
      CDI epidemiology were associated with the rapid emergence of hypervirulent
      strains of C. difficile, now collectively referred to as NAP1/BI/027 strains. The
      discovery of new epidemic strains of C. difficile has provided a unique
      opportunity for retrospective and prospective studies that have sought to
      understand how these strains have essentially replaced more historical strains as
      a major cause of CDI. Moreover, detailed studies on the pathogenesis of
      NAP1/BI/027 strains are leading to new hypotheses on how this emerging strain
      causes severe disease and is more commonly associated with epidemics. In this
      review, we provide an overview of CDI, discuss critical mechanisms of C.
      difficile virulence, and explain how differences in virulence-associated factors
      between historical and newly emerging strains might explain the hypervirulence
      exhibited by this pathogen during the past decade.

PMID- 24296577
TI  - Imaging: Advancing dysplasia and neoplasia detection in Barrett oesophagus.

PMID- 24296574
TI  - Host-directed therapeutics for tuberculosis: can we harness the host?
AB  - Treatment of tuberculosis (TB) remains challenging, with lengthy treatment
      durations and complex drug regimens that are toxic and difficult to administer.
      Similar to the vast majority of antibiotics, drugs for Mycobacterium tuberculosis
      are directed against microbial targets. Although more effective drugs that target
      the bacterium may lead to faster cure of patients, it is possible that a
      biological limit will be reached that can be overcome only by adopting a
      fundamentally new treatment approach. TB regimens might be improved by including
      agents that target host pathways. Recent work on host-pathogen interactions, host
      immunity, and host-directed interventions suggests that supplementing anti-TB
      therapy with host modulators may lead to shorter treatment times, a reduction in
      lung damage caused by the disease, and a lower risk of relapse or reinfection. We
      undertook this review to identify molecular pathways of the host that may be
      amenable to modulation by small molecules for the treatment of TB. Although
      several approaches to augmenting standard TB treatment have been proposed, only a
      few have been explored in detail or advanced to preclinical and clinical studies.
      Our review focuses on molecular targets and inhibitory small molecules that
      function within the macrophage or other myeloid cells, on host inflammatory
      pathways, or at the level of TB-induced lung pathology.

PMID- 24296578
TI  - Viral hepatitis: Subinfectious HCV exposure.

PMID- 24296579
TI  - Faecal microbiota transplantation in 2013: developing human gut microbiota as a
      class of therapeutics.
AB  - Although the idea of faecal transplantation dates back many decades, only with
      advances in scientific technologies can we begin systematic development of this
      new class of therapeutics. The primary focus remains on treatment of Clostridium
      difficile infection-new applications are beginning to emerge, but a long journey
      remains ahead.

PMID- 24296580
TI  - Hepatocellular carcinoma: New insight into angiogenesis in hepatocellular
      carcinoma: involvement of microRNA-26a.

PMID- 24296573
TI  - Salmonella pathogenicity and host adaptation in chicken-associated serovars.
AB  - Enteric pathogens such as Salmonella enterica cause significant morbidity and
      mortality. S. enterica serovars are a diverse group of pathogens that have
      evolved to survive in a wide range of environments and across multiple hosts. S.
      enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a
      restricted host range, in which they are typically associated with one or a few
      host species, while S. Enteritidis and S. Typhimurium have broad host ranges.
      This review examines how S. enterica has evolved through adaptation to different
      host environments, especially as related to the chicken host, and continues to be
      an important human pathogen. Several factors impact host range, and these include
      the acquisition of genes via horizontal gene transfer with plasmids, transposons,
      and phages, which can potentially expand host range, and the loss of genes or
      their function, which would reduce the range of hosts that the organism can
      infect. S. Gallinarum, with a limited host range, has a large number of
      pseudogenes in its genome compared to broader-host-range serovars. S. enterica
      serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may
      help them colonize poultry more efficiently. The ability to colonize different
      hosts also involves interactions with the host's immune system and commensal
      organisms that are present. Thus, the factors that impact the ability of
      Salmonella to colonize a particular host species, such as chickens, are complex
      and multifactorial, involving the host, the pathogen, and extrinsic pressures. It
      is the interplay of these factors which leads to the differences in host ranges
      that we observe today.

PMID- 24296581
TI  - IBD: Measuring what counts--endoscopic assessment in IBD.

PMID- 24296582
TI  - Hepatitis: Immunoregulation in pregnancy and perinatal transmission of HCV.

PMID- 24296583
TI  - The complexity of globus: a multidisciplinary perspective.
AB  - Globus is a topic of interest for many specialties including otorhinolaryngology,
      gastroenterology and psychiatry/psychosomatic medicine, but, although many
      hypotheses have been suggested, key questions about its aetiology remain. This
      Review provides an overview of the extensive literature concerning this topic and
      discusses the quality of the evidence to date. Globus has been associated with
      oropharyngeal structural lesions, upper oesophageal sphincter disorders,
      oesophageal disorders, GERD, psychosocial factors and psychiatric comorbidity.
      However, findings are often contradictory and the literature remains highly
      inconclusive. Indeed, with the exception of patients with structural-based
      globus, the Rome III criteria for functional globus only apply to a subgroup of
      patients with idiopathic globus. In clinical reality, there exists a group of
      patients who present with idiopathic (nonstructural) globus, but nevertheless
      have dysphagia, odynophagia or GERD-exclusion criteria for globus diagnosis
      according to Rome III. The symptomatology of patients with globus might be
      broader than previously thought. It is therefore crucial to approach globus not
      from one single perspective, but from a multifactorial point of view, with focus
      on the coexistence and/or interactions of different mechanisms in globus
      pathogenesis. This approach could be translated to clinical practice by adopting
      a multidisciplinary method to patients presenting with globus. 

PMID- 24296584
TI  - Asymptomatic bacteriuria and urinary tract infections in special patient groups:
      women with diabetes mellitus and pregnant women.
AB  - PURPOSE OF REVIEW: Asymptomatic bacteriuria (ASB) and urinary tract infections
      (UTIs) in women with diabetes mellitus and during pregnancy are common and can
      have far-reaching consequences for the woman and neonate. This review describes
      epidemiology, risk factors, complications and treatment of UTI and ASB according
      to recent developments in these two groups. RECENT FINDINGS: Most articles
      addressing the epidemiology and risk factors of ASB and UTI in diabetic and
      pregnant women confirmed existing knowledge. New insights were obtained in the
      association between sodium-glucose cotransporter-2 (SGLT2) inhibitors, as
      medication for diabetes mellitus type 2, and a small increased risk for UTI due
      to glucosuria and the possible negative effects of UTI, including urosepsis,on
      bladder and kidney function in diabetic women. Predominantly, potential long-term
      effects of antibiotic treatment of ASB or UTI during pregnancy on the neonate
      have received attention, including antibiotic resistance and epilepsy. SUMMARY:
      SGLT2 inhibitors were associated with a small increased risk for UTI, UTI in
      diabetic women may lead to bladder and kidney dysfunction, and antibiotic
      treatment of ASB and UTI during pregnancy was associated with long-term effects
      on the neonate. Up-to-date research on the effectiveness and long-term effects of
      ASB screening and treatment policies, including group B Streptococcus bacteriuria
      in pregnancy, is warranted to inform clinical practice.

PMID- 24296585
TI  - Emerging strategies to deplete the HIV reservoir.
AB  - PURPOSE OF REVIEW: This review highlights recent studies undertaken to further
      advance the search for successful approaches to eradicate HIV infection. RECENT
      FINDINGS: Small pharmacological compounds such as histone deacetylase inhibitors,
      inhibitors of bromodomain and extraterminal proteins such as JQ1, and protein
      kinase C activators such as bryostatin and prostratin are proposed as putative
      candidates for inducing the expression of latent HIV in a so-called 'shock and
      kill' or 'kick and kill' strategy for HIV eradication. However, in order to
      achieve viral clearance, it is thought likely these compounds will have to be
      administered in concert with strategies that augment clearance of virus-infected
      cells in patients that have long been aviremic on successful antiretroviral
      therapy (ART). Several candidate therapies for this purpose are at hand, such as
      therapeutic HIV vaccines - recently shown to promote robust cytotoxic T cell
      responses and blunt viral rebound after ART interruption in clinical studies. HIV
      infected patients treated during early infection may be ideal candidates for
      early studies to test these strategies, as early ART has been shown to limit the
      establishment of an HIV reservoir. SUMMARY: HIV latency is multifactorial and
      thus the eradication of HIV infection may require multiple approaches.
      Translational efforts employing pharmacological methods to target HIV latency
      should evaluate in parallel the additional potential benefits of invigorating the
      immune response of HIV-infected individuals, and limiting the size of the
      reservoir via early ART.

PMID- 24296586
TI  - Ventilator-associated pneumonia in neonatal patients: an update.
AB  - Ventilator-associated pneumonia (VAP) is a serious complication related to
      mechanical ventilation in the neonatal period. However, lack of a specific
      definition and difficulties obtaining noncontaminated samples of the lower
      respiratory airway render microbiological diagnosis and etiological treatment
      extremely difficult. Thus far, only few studies have approached VAP using
      accepted Centers for Disease Control and Prevention criteria and reliable
      sampling techniques. In recent years, however, the blind-protected
      bronchoalveolar lavage technique with protected specimen brush and the
      development of validated biomarkers have attempted to overcome the diagnostic
      difficulties and assess the response to therapy. This updated review on neonatal
      VAP aims to stimulate neonatologists' interest in this subtle but serious
      complication of mechanical ventilation.

PMID- 24296588
TI  - Characteristics of long non-coding RNA and its relation to hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with
      high prevalence and lethality. However, the underlying mechanism for HCC has not
      been entirely elucidated. Recent studies have highlighted the roles of long non
      coding RNAs (lncRNAs) in carcinogenesis, and it is suggested that they might play
      critical roles in HCC progression. Here, we will briefly introduce the biology of
      lncRNAs, emphasizing the mechanisms and emerging roles of HCC-related lncRNAs. To
      date, HCC-related lncRNAs are demonstrated to influence the life cycle of genes
      by various means including epigenetic silencing, splicing regulation, lncRNA
      miRNA interaction, lncRNA-protein interaction and genetic variation. Moreover,
      they can participate in diverse biological processes involved in HCC progression
      through impacts upon cell proliferation, apoptosis, invasion and metastasis and
      angiogenesis. Since lncRNA can present in body fluid and have good specificity
      and accessibility, some HCC-related lncRNAs are suggested to be useful as novel
      potential biomarkers for HCC diagnosis, prognosis and prediction of response to
      therapy. Those HCC-related lncRNAs may provide potential novel therapeutic
      targets for HCC and other diseases.

PMID- 24296589
TI  - Integrating gene expression and epidemiological data for the discovery of genetic
      interactions associated with cancer risk.
AB  - Dozens of common genetic variants associated with cancer risk have been
      identified through genome-wide association studies (GWASs). However, these
      variants only explain a modest fraction of the heritability of disease. The
      missing heritability has been attributed to several factors, among them the
      existence of genetic interactions (G * G). Systematic screens for G * G in model
      organisms have revealed their fundamental influence in complex phenotypes. In
      this scenario, G * G overlap significantly with other types of gene and/or
      protein relationships. Here, by integrating predicted G * G from GWAS data and
      complex- and context-defined gene coexpression profiles, we provide evidence for
      G * G associated with cancer risk. G * G predicted from a breast cancer GWAS
      dataset identified significant overlaps [relative enrichments (REs) of 8-36%,
      empirical P values < 0.05 to 10(-4)] with complex (non-linear) gene coexpression
      in breast tumors. The use of gene or protein data not specific for breast cancer
      did not reveal overlaps. According to the predicted G * G, experimental assays
      demonstrated functional interplay between lipoma-preferred partner and
      transforming growth factor-beta signaling in the MCF10A non-tumorigenic mammary
      epithelial cell model. Next, integration of pancreatic tumor gene expression
      profiles with pancreatic cancer G * G predicted from a GWAS corroborated the
      observations made for breast cancer risk (REs of 25-59%). The method presented
      here can potentially support the identification of genetic interactions
      associated with cancer risk, providing novel mechanistic hypotheses for
      carcinogenesis.

PMID- 24296591
TI  - Editorial: Jack of all trades? The versatility of IL-4 in CD8+ T cell polarity.

PMID- 24296590
TI  - Regulatory T cells and the immune aging process: a mini-review.
AB  - Constant exposure to new and persisting antigens and the need to replace cellular
      attrition with newly built cells lead to profound remodeling of the immune system
      after the age of 50 years. The impact of the immunosenescence process varies
      amongst the different cellular subsets represented within the immune system.
      Emerging data suggest that progressive aging significantly affects frequencies,
      subset distribution and functional competence of regulatory T cells (Tregs).
      Given the central role of Tregs in immune homeostasis, age-related loss of Treg
      function would be predicted to cause excessive immunity, encountered in elderly
      humans as a syndrome of chronic, smoldering inflammation as well as the age
      related increase in the risk for autoimmunity. Conversely, age-dependent gain of
      Treg activity would result in failing immunity, such as the rising risk of
      malignancies and infections amongst the elderly. Emerging data suggest that some
      Treg populations, specifically naturally occurring Tregs, seem to accumulate with
      advancing age, whereas inducible Tregs appear to be less available in the older
      host. More studies are necessary to elucidate functional competence of old Tregs,
      with an emphasis on comparing the efficacy of young and old Tregs for defined
      functional domains. Mechanisms of declining Treg inducibility are not understood,
      but may provide an opportunity for targeted immunomodulation in the elderly. On
      the horizon is the potential to develop novel therapeutic interventions that
      target Tregs to make the elderly more efficient in fighting cancers and
      infections and dampen the risk for senescence-associated inflammation.

PMID- 24296592
TI  - Editorial: "Presenting" an adaptive role for AMPK.

PMID- 24296575
TI  - Nitrogen assimilation in Escherichia coli: putting molecular data into a systems
      perspective.
AB  - We present a comprehensive overview of the hierarchical network of intracellular
      processes revolving around central nitrogen metabolism in Escherichia coli. The
      hierarchy intertwines transport, metabolism, signaling leading to
      posttranslational modification, and transcription. The protein components of the
      network include an ammonium transporter (AmtB), a glutamine transporter (GlnHPQ),
      two ammonium assimilation pathways (glutamine synthetase [GS]-glutamate synthase
      [glutamine 2-oxoglutarate amidotransferase {GOGAT}] and glutamate dehydrogenase
      [GDH]), the two bifunctional enzymes adenylyl transferase/adenylyl-removing
      enzyme (ATase) and uridylyl transferase/uridylyl-removing enzyme (UTase), the two
      trimeric signal transduction proteins (GlnB and GlnK), the two-component
      regulatory system composed of the histidine protein kinase nitrogen regulator II
      (NRII) and the response nitrogen regulator I (NRI), three global transcriptional
      regulators called nitrogen assimilation control (Nac) protein, leucine-responsive
      regulatory protein (Lrp), and cyclic AMP (cAMP) receptor protein (Crp), the
      glutaminases, and the nitrogen-phosphotransferase system. First, the structural
      and molecular knowledge on these proteins is reviewed. Thereafter, the activities
      of the components as they engage together in transport, metabolism, signal
      transduction, and transcription and their regulation are discussed. Next, old and
      new molecular data and physiological data are put into a common perspective on
      integral cellular functioning, especially with the aim of resolving
      counterintuitive or paradoxical processes featured in nitrogen assimilation.
      Finally, we articulate what still remains to be discovered and what general
      lessons can be learned from the vast amounts of data that are available now.

PMID- 24296593
TI  - Is time to flap coverage of open tibial fractures an independent predictor of
      flap-related complications?
AB  - OBJECTIVES: The importance of the timing of flap coverage of open tibial shaft
      fractures remains controversial. Many studies have shown increased complications
      and infection rates associated with delay in coverage but have not controlled for
      risk factors that might be associated with both delay in coverage and
      complications. We hypothesized that the timing of flap coverage of open tibial
      fractures is not predictive of complications after controlling for known risk
      factors. DESIGN: Retrospective review. SETTING: Level I trauma center. PATIENTS:
      Sixty-nine patients treated for acute tibial fractures (45 tibial shaft, 17
      plateau, and 12 pilon fractures) at our center from 2004 through 2009 required 74
      flaps. Patients requiring flaps later for wound breakdown or infection were
      excluded. INTERVENTION: Electronic records and prospective trauma database were
      reviewed. All fractures were AO classified by a trauma fellowship-trained
      orthopaedic surgeon. MAIN OUTCOME MEASUREMENTS: Primary outcome was flap
      complication, defined as infection or other flap-related adverse outcome
      requiring surgical treatment. Logistic regression analysis was conducted.
      RESULTS: A logistic regression model that separated the first 7 days after injury
      from subsequent days found no increased risk for days 1 through 7. The odds of
      complications, and of infection in particular, increased by 11% and 16%,
      respectively, for each day beyond day 7 (P < 0.04). CONCLUSIONS: Even after
      controlling for known risk factors for complications, including injury severity,
      time to flap coverage was a significant predictor of complications. LEVEL OF
      EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24296594
TI  - Intrapelvic reduction and buttress screw stabilization of dome impaction of the
      acetabulum: a technical trick.
AB  - Superomedial impaction of the anterior dome of the acetabulum is a known risk
      factor for poor outcomes after open reduction and internal fixation of acetabular
      fractures. The authors, using the anterior intrapelvic (modified Stoppa) approach
      to the acetabulum, describe a novel technique to help reduce and stabilize
      marginal impaction of the acetabular dome. In the senior author's experience,
      this technique has been helpful to achieve adequate reduction and stabilization.

PMID- 24296595
TI  - The homeless orthopaedic trauma patient: follow-up, emergency room usage, and
      complications.
AB  - OBJECTIVES: To review homeless patients with orthopaedic trauma injuries and
      examine their emergency room (ER) usage, follow-up rates, and complication rates.
      DESIGN: Retrospective chart review. SETTING: Patients presenting to a level 1
      trauma center with orthopaedic trauma injuries from 2001 to 2010.
      PATIENTS/PARTICIPANTS: Sixty-three uninsured homeless patients and 63 uninsured
      nonhomeless patients with orthopaedic trauma injuries were included.
      INTERVENTION: Homeless patients with orthopaedic trauma were identified through
      ER intake sheets and current procedural terminology code searches. MAIN OUTCOME
      MEASUREMENTS: ER usage, orthopaedic clinic follow-up, and complications. RESULTS:
      After the index visit to the ER for their orthopaedic trauma injuries, homeless
      patients demonstrated more ER visits and had fewer orthopaedic clinic follow-up
      visits than nonhomeless patients (P < 0.001). There were no significant
      differences among the type of complications (none, infection, hardware failure,
      and nonunion) between the homeless and the nonhomeless patients (P = 0.23).
      Operative homeless patients returned to the orthopaedic clinic for follow-up more
      than nonoperative homeless patients (mean = 5.4, SD = 7.6; and mean = 1.2, SD =
      1.5, respectively; P < 0.001). CONCLUSIONS: Our data are the first to examine the
      problems associated with homelessness in the patient with orthopaedic trauma and
      demonstrate an increased challenge in the follow-up care. The orthopaedic surgeon
      must consider these issues in managing this complex patient population. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24296596
TI  - The effect of sleep deprivation on a resident's situational awareness in a trauma
      scenario.
AB  - OBJECTIVES: Situational awareness (SA) refers to the perception of elements in
      one's environment, the comprehension of their meaning, and the projection of
      their status in the near future. The SA global assessment technique (SAGAT) is an
      assessment tool validated for use in a trauma simulation. The goal of this study
      was to determine the effect of sleep deprivation on residents' performance in a
      trauma simulation, evaluated by the SAGAT. METHODS: A power analysis determined
      that 9 residents would be needed to show a significant difference in SAGAT scores
      (7%). Therefore, 9 surgical residents on an intensive care unit rotation
      underwent 2 trauma simulations. One session was performed in the rested
      condition, and the other was for postcall. The SAGAT was used to evaluate the
      residents' performance. The rested and postcall scores were compared. RESULTS:
      Using a paired t test, the SAGAT scores were analyzed. The average rested score
      was 80.13% (range, 50%-94%), and the sleep-deprived score was 80.09% (range, 72%
      91%). There was no significant difference between the residents' rested and the
      postcall SAGAT scores (P = 0.99). CONCLUSIONS: From this study, the resident SA
      in a trauma simulation does not seem to be affected by 1 night of sleep
      deprivation, as demonstrated by the lack of significant difference in SAGAT
      scores; however, more research in this area is needed. LEVEL OF EVIDENCE:
      Prognostic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24296597
TI  - Negative pressure wound therapy and external fixation device: a simple way to
      seal the dressing.
AB  - Negative pressure therapy is widely applied to treat lower limb trauma. However,
      sealing a negative pressure dressing in the presence of an external fixation
      device may be difficult and time consuming. Therefore, screws, pins, wires, etc,
      may preclude the vacuum, preventing the plastic drape to perfectly adhere to the
      foam. To maintain the vacuum, we tried to prevent air leaking around the screws
      putting bone wax at the junction between the pins and the plastic drape. This
      solution, in our hands, avoids air leakage and helps maintain vacuum in a fast
      and inexpensive way.

PMID- 24296598
TI  - The impact of preoperative coronal plane deformity on proximal humerus fixation
      with endosteal augmentation.
AB  - OBJECTIVES: To examine the impact of preoperative coronal plane deformity on
      functional and radiographic outcomes on endosteal strut augmentation of proximal
      humerus fracture fixation. DESIGN: Single surgeon, retrospective analysis of a
      prospective database. Case series. SETTING: Academic level 1 trauma center.
      PATIENTS/PARTICIPANTS: Seventy-two patients with isolated proximal humerus
      fractures fulfilled all inclusion/exclusion criteria with a minimum follow-up of
      12 months. INTERVENTION: Proximal humerus open reduction internal fixation with a
      laterally placed proximal humeral locking plate and endosteal placement of an
      allograft fibula treated through the anterolateral approach. MAIN OUTCOME
      MEASUREMENTS: Global functional outcome as determined by the Disabilities of the
      Arm, Shoulder and Hand (DASH) score and Short Form 36 physical function. Shoulder
      specific functional outcome as determined by the Constant-Murley and the
      University of California Los Angeles shoulder scores. RESULTS: The mean age was
      62 years old (range, 26-90 years). There were 32 varus fractures (neck-shaft
      angle, 110.8 degrees) and 40 valgus fractures (neck-shaft angle, 168.9 degrees).
      There was no significant difference in the initial postoperative (varus: 132.5
      degrees, valgus: 135.5 degrees) and final (varus: 129.9 degrees, valgus: 132.2
      degrees) neck-shaft angles or change in humeral height (varus: 0.94 mm, valgus:
      1.48 mm). There were no significant differences in functional outcomes [Constant
      (varus: 85.2, valgus: 88.7) DASH (varus: 21.4, valgus: 13.9), University of
      California Los Angeles (28.6, varus 30.4), and Short Form 36 (varus: 66.8,
      valgus: 59.1)]. There were 2 patients in the valgus group and 3 patients in the
      varus group with an asymptomatic humeral head screw penetration (mean Constant
      84.5, DASH 9.5). There was 1 deep infection in the varus group and 2 in the
      valgus group necessitating implant removal after fracture union. There was 1 case
      of avascular necrosis in the valgus group (DASH 19.4, Constant 73). CONCLUSIONS:
      There were no significant differences in complication rates, radiographic, or
      clinical outcomes between fractures presenting with preoperative varus coronal
      displacement compared with those presenting with valgus coronal displacement. The
      equivalent outcomes may be attributed to the uniform operative technique and
      fibular strut augmentation used by the primary surgeon. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24296599
TI  - Comparison of radiographic stress tests for syndesmotic instability of supination
      external rotation ankle fractures: a cadaveric study.
AB  - OBJECTIVE: According to the classification of Lauge-Hansen, supination-external
      rotation IV (OTA 44-B) injuries should not have syndesmotic instability; yet,
      several studies have suggested disruption is present in up to 40% of these
      injuries based on stress tests. In this study, we examine various stress
      radiographic parameters in a cadaver model of supination-external rotation IV
      equivalent injury. We hypothesize that external rotation stress testing and
      widening of the medial clear space do not always represent syndesmotic
      instability. Rather, the better predictor of syndesmotic instability will be an
      increased tibia-fibula clear space with the lateral stress test. METHODS: Eleven
      fresh frozen human lower limbs were each secured into a custom frame. External
      rotation stress test was performed by applying an external moment of 7.5 Nm, and
      lateral stress test was performed by applying 100 N lateral pull at the distal
      fibula. True mortise radiographs were taken of intact ankles and while performing
      external rotation and lateral stress tests at each stage of sequentially
      sectioning the ankle ligaments. The deltoid ligament was sectioned first, then
      anterior-inferior tibiofibular ligament, posterior-inferior tibiofibular
      ligament, and interosseous membrane. Tibiofibular clear space and medial clear
      space were measured on each radiograph. RESULTS: External rotation stress test
      produced significant medial clear space widening when the deltoid ligaments were
      sectioned (P < 0.05). Lateral stress test produced no significant widening of the
      tibiofibular clear space until interosseous membranes were sectioned (P < 0.05).
      CONCLUSIONS: Lateral stress test with widening of the tibiofibular clear space is
      the preferred indicator of syndesmotic instability. The external rotation stress
      is a poor indicator of syndesmotic injury in the setting of deltoid ligament
      injury.

PMID- 24296600
TI  - Metaphyseal screw augmentation of the LISS-PLT plate with polymethylmethacrylate
      improves angular stability in osteoporotic proximal third tibial fractures: a
      biomechanical study in human cadaveric tibiae.
AB  - OBJECTIVES: The incidence of osteoporotic proximal tibial fractures has increased
      during the last 2 decades. A promising approach in osteoporotic fracture fixation
      is polymethylmethacrylate-based cement augmentation of implants to gain better
      implant purchase in the bone. This study investigates the biomechanical benefits
      of screw augmentation in less invasive stabilization system-proximal lateral
      tibial (LISS-PLT) plates in cadaveric extraarticular comminuted proximal tibial
      fractures (OTA-41-A3.3). METHODS: Standardized extraarticular proximal tibial
      fractures were stabilized with the LISS-PLT plate in 6 paired osteoporotic
      cadaveric tibiae. Bone mineral density was measured with high-resolution,
      quantitative computed tomography scans to identify bone quality. In the augmented
      group, the 5 proximal screws of the LISS-PLT plate were augmented with 1 mL of
      bone cement each, whereas the contralateral tibia was instrumented conventionally
      as the control. Cyclic axial loading was applied to each specimen with a starting
      load of 150 N, using a ramp of 0.05 N per cycle to 10-mm axial displacement.
      Varus displacement was identified from anterior-posterior radiographs. RESULTS:
      Bone mineral density showed no significant difference between the 2 groups (P =
      0.47). The nonaugmented group reached 9417 load cycles (SD 753) until failure,
      compared with 14,792 load cycles (SD 2088) in the augmented group (P = 0.002). In
      the early-onset failure (deformation at 8250 load cycles), varus displacement was
      significantly smaller in the augmented group (0.46 degrees, SD 0.6) than in the
      nonaugmented group (3.23 degrees, SD 1.7) (P = 0.01). CONCLUSIONS: This
      biomechanical study showed that cement augmentation of the LISS-PLT plate screws
      in osteoporotic proximal extraarticular tibial fractures significantly lowers the
      propensity toward screw migration and secondary varus displacement.

PMID- 24296601
TI  - Distal tibial periarticular nonunions: ankle salvage with bone transport.
AB  - A nonunion of the distal tibial metaphysis in close proximity to the articular
      surface is a challenging clinical problem. Many of the commonly used techniques
      in a surgeon's treatment armamentarium can be ineffective because of the relative
      lack of distal bone stock. This study describes a technique of en bloc excision
      of all infected or nonunited distal tibial bone with an application of a circular
      external fixator and limb shortening. After treatment with parental antibiotics,
      when appropriate, and docking of the distal excision site, distraction
      osteogenesis of the proximal tibia is performed with a second circular frame.

PMID- 24296604
TI  - Pregnancy following transplantation.

PMID- 24296605
TI  - The authors' reply.

PMID- 24296606
TI  - Lengthy follow-up after liver transplantation for nodular regenerative
      hyperplasia in human immunodeficiency virus-infected patients: does the disease
      recur?

PMID- 24296607
TI  - Do no harm: calcium and phosphate supplementation in kidney transplant
      recipients.

PMID- 24296608
TI  - Deceased organ donation and the Nicholas effect.

PMID- 24296609
TI  - Adherence to hepatitis B immunoglobulin (HBIG) after liver transplantation.

PMID- 24296610
TI  - A low-dose beta1-blocker effectively and safely slows the heart rate in patients
      with acute decompensated heart failure and rapid atrial fibrillation.
AB  - OBJECTIVE: Recently, we reported that low-dose landiolol (1.5 ug.kg(-1).min(-1)),
      an ultra-short-acting beta-blocker, safely decreased the heart rate (HR) in
      patients with acute decompensated heart failure (ADHF) and sinus tachycardia,
      thereby improving cardiac function. We investigated whether low-dose landiolol
      effectively decreased the HR in ADHF patients with rapid atrial fibrillation
      (AF). METHODS: We enrolled 23 ADHF patients with rapid AF (HR >=120 beats.min(-1)
      and New York Heart Association class III-IV) and systolic heart failure (SHF: n =
      12) or diastolic heart failure (DHF: n = 11) who received conventional therapy
      with diuretics, vasodilators, and/or low-dose inotropes. They were administered
      continuous intravenous infusion of low-dose landiolol (1.0-2.0 ug.kg(-1).min(
      1)), and their electrocardiograms and blood pressures were monitored for 24 h
      thereafter. RESULTS: Two hours after starting landiolol, the HR was reduced
      significantly (22%), without a reduction in blood pressure, and remained constant
      thereafter. The HR reduction 2 h after landiolol administration was significantly
      greater in the DHF group than in the SHF group. No incidence of hypotension was
      recorded. CONCLUSIONS: Digitalis or amiodarone is currently recommended for HR
      control in ADHF patients with rapid AF. Our results showed that continuous
      infusion of low-dose landiolol may also be useful as first-line therapy in these
      patients.

PMID- 24296611
TI  - Amino acid assisted templating synthesis of hierarchical zeolitic imidazolate
      framework-8 for efficient arsenate removal.
AB  - We report the strategy of using the cationic surfactant cetyltrimethylammonium
      bromide (CTAB) and amino acid L-histidine (His) as co-templates to produce
      hierarchical ZIF-8 in an aqueous system at room temperature. The hierarchical ZIF
      8 had both meso- and microporous structure, resulting in a high mesopore volume
      as well as specific surface area which can be controlled by the synthesis
      conditions. We put forward the hypothesis for the formation of a mesoporous
      structure and the enhancement of the porosity of ZIF-8 that the histidine plays a
      key role on the stabilization of CTAB micelles and avoiding the production of
      unexpected by-products therefore promotes the fabrication of pure phase ZIF-8
      containing the mesopores interconnected with micropores. The prepared
      hierarchical ZIF-8 exhibited an excellent performance as a new kind of porous
      absorbent for efficient removal of the toxic arsenate.

PMID- 24296612
TI  - More than a billion people taking statins?: Potential implications of the new
      cardiovascular guidelines.

PMID- 24296614
TI  - Metformin-induced hemolytic anemia.
AB  - OBJECTIVE: To report a rare side effect of metformin, an oral antidiabetic drug
      that is used for the treatment of type 2 diabetes mellitus. CLINICAL PRESENTATION
      AND INTERVENTION: A 17-year-old boy was hospitalized for receiving acute
      lymphoblastic leukemia treatment that was composed of vincristine, L
      asparaginase, daunorubicin, and prednisone. Hyperglycemia was determined without
      any clinical sign and metformin was started for steroid-induced insulin
      resistance. On the second day of metformin treatment, the patient's hemoglobin
      level decreased, and a direct Coombs test was positive for immunoglobulin G but
      negative for complement. An indirect Coombs test was negative. The glucose-6
      phosphate dehydrogenase level was within the normal range. Drug-induced hemolytic
      anemia was suspected and metformin was discontinued. The jaundice gradually
      disappeared and there was no requirement for red blood cell transfusions.
      CONCLUSION: This case showed that physicians should be aware of the potential
      side effect of metformin although it is infrequent.

PMID- 24296615
TI  - A new approach to the synthesis of functional derivatives of nido-carborane:
      alkylation of [9-MeS-nido-7,8-C2B9H11]-.
AB  - A series of asymmetrically substituted sulfonium derivatives of nido-carborane [9
      R(Me)S-nido-7,8-C2B9H11] (R = Et, Pr, Bu, Bn, CH=CH2, CH2CH=CH2, CH2C=CH,
      CH=C=CH2) were prepared by alkylation of the 9-methylthio-nido-7,8-carborane. The
      synthesized compounds are the first examples of diastereomers combining nido
      carborane and sulfonium chiral centers.

PMID- 24296617
TI  - Downregulation of microRNA-19b contributes to angiotensin II-induced
      overexpression of connective tissue growth factor in cardiomyocytes.
AB  - OBJECTIVES: The present study was designed to decipher the molecular mechanisms
      underlying angiotensin (Ang) II-induced overexpression of connective tissue
      growth factor (CTGF) in cultured cardiomyocytes. METHODS: Cardiomyocytes isolated
      from 1- to 3-day-old neonatal rats were cultured and treated with 100 nM Ang II
      with or without pretreatment with 10 nM telmisartan, an Ang II type 1 receptor
      antagonist. The role of microRNA (miR)-19b in the regulation of Ang II-induced
      CTGF expression was evaluated in cultured cardiomyocytes with quantitative real
      time reverse transcription polymerase chain reaction and Western blot analysis.
      RESULTS: We provide several lines of evidence to show that miR-19b contributes to
      the Ang II-induced overexpression of CTGF in cultured cardiomyocytes. Firstly,
      administration of Ang II decreased the level of miR-19b dramatically (p < 0.05
      vs. control), which was abolished by telmisartan. Secondly, Ang II increased the
      level of CTGF significantly (p < 0.05 vs. control), which was also prevented by
      pretreatment with telmisartan. Thirdly, overexpression of miR-19b decreased CTGF
      levels (p < 0.05 vs. control). Finally, transfection of miR-19b into
      cardiomyocytes prevented the upregulation of CTGF induced by Ang II. CONCLUSION:
      Downregulation of miR-19b contributes to Ang II-induced overexpression of CTGF in
      cultured cardiomyocytes.

PMID- 24296618
TI  - The cost of antiretroviral drug resistance in HIV-positive patients.
AB  - INTRODUCTION: Antiretroviral (ARV) drug resistance limits treatment choices,
      often necessitating the selection of drugs with less desirable pill burdens,
      toxicity profiles, drug interactions and dosing schedules, and may increase cost.
      We examine the impact of resistance on the cost of HIV care. METHODS: All adult
      HIV-positive individuals newly referred for HIV care from 1 January 2007 to 1
      January 2011 and followed until 31 December 2011 at the Southern Alberta Clinic,
      Calgary, AB, Canada, were included. We determined the cost of all ARV drugs, and
      HIV-related outpatient and inpatient care, reported as mean per patient per month
      (PPPM) costs in 2011 Canadian dollars (CDN). RESULTS: Overall, 78% of patients
      received genotypic antiretroviral resistance testing (GART); 57% among ARV-naive
      patients, 21% after suspected viral failure, and 20% during a treatment
      interruption. Resistance was detected in 6%, 49% and 21% of all tests
      respectively. The total mean PPPM cost for patients with GART was CDN 1,179.
      Patients with primary resistance had mean total PPPM costs of CDN 956. Patients
      with no resistance had mean PPPM costs of CDN 1,058, by contrast with the CDN
      1,291 costs of patients with secondary/acquired resistance. Mean costs for one,
      two or three ARV class resistance was CDN 1,278, 1,337 and 1,801, respectively.
      Mean PPPM costs increased by 31% from CDN 1,068 to 1,396, respectively, before
      and after a positive resistance test. CONCLUSIONS: Transmission of resistant
      virus as well as emergence of resistance during ARV therapy leads to increased
      costs. Mean costs increased by number of resistant classes. Routine GART and
      optimizing ARV regimens to avoid resistance might minimize the long-term costs of
      HIV care.

PMID- 24296619
TI  - Putative roles for PI3K alpha and delta isoforms in refractory mantle cell
      lymphoma.

PMID- 24296616
TI  - Rapamycin induces pluripotent genes associated with avoidance of replicative
      senescence.
AB  - Primary rodent cells undergo replicative senescence, independent from telomere
      shortening. We have recently shown that treatment with rapamycin during passages
      3-7 suppressed replicative senescence in rat embryonic fibroblasts (REFs), which
      otherwise occurred by 10-14 passages. Here, we further investigated rapamycin
      primed cells for an extended number of passages. Rapamycin-primed cells continued
      to proliferate without accumulation of senescent markers. Importantly, these
      cells retained the ability to undergo serum starvation- and etoposide-induced
      cell cycle arrest. The p53/p21 pathway was functional. This indicates that
      rapamycin did not cause either transformation or loss of cell cycle checkpoints.
      We found that rapamycin activated transcription of pluripotent genes, oct-4, sox
      2, nanog, as well as further upregulated telomerase (tert) gene. The rapamycin
      derived cells have mostly non-rearranged, near-normal karyotype. Still, when
      cultivated for a higher number of passages, these cells acquired a chromosomal
      marker within the chromosome 3. We conclude that suppression mTORC1 activity may
      prevent replicative senescence without transformation of rodent cells. 

PMID- 24296621
TI  - Ordered fibrillar morphology of donor-acceptor conjugated copolymers at multiple
      scales via blending with flexible polymers and solvent vapor annealing: insight
      into photophysics and mechanism.
AB  - The ordered, aligned fibrillar morphology at multiple scales of a donor-acceptor
      (D-A) conjugated copolymer of 3,6-bis-(thiophen-2-yl)-N,N'-bis(2-octyl-1-dodecyl)
      1,4-dioxo-pyrrolo[3,4-c]pyrrole and thieno[3,2-b]thiophene (PDBT-TT) was prepared
      via blending with flexible polymers (PS13.7k, PDBT-TT/PS = 1/10 w/w) followed by
      chloroform (CF) solvent vapor annealing (SVA) for 24 h. The aligned fibrillar
      bundles were of about 500 nm width, consisting of parallel aligned nanofibrils of
      ab. 10 nm width. It was found that the direction of backbones in nanofibrils was
      parallel to the long axis of nanofibrils, which implied an intense intra-chain
      conjugation associated with extended backbones and J-aggregation of PDBT-TT. This
      ordered morphology corresponded to the characteristic photophysical features of
      (i) red-shifted absorption arising from J-aggregation, (ii) larger Davydov
      splitting, (iii) the prevailing absorbance of J-aggregation over H-aggregation in
      its UV-Vis spectrum and (iv) more red-shifted max photoluminescence emission,
      compared with the films prepared via the other methods. By investigating the
      Raman spectra and XRD profiles, it is proposed that the origin of the best
      morphological and photophysical order is the combination of blending and SVA. The
      limited and "flexible" space formed due to phase separation between PDBT-TT and
      PS facilitated the motion of rigid PDBT-TT chains and promoted their stacking
      order as templates, and CF vapor assisted the conformational transition of chains
      to more "coil-like" to help them reorganize in a thermodynamic stable way. 

PMID- 24296622
TI  - Lack of evidence to support aspects of the NICE neutropenic sepsis clinical
      guideline CG151.

PMID- 24296620
TI  - Protein arginine methylation of non-histone proteins and its role in diseases.
AB  - Protein arginine methyltransferases (PRMTs) are a family of enzymes that can
      methylate arginine residues on histones and other proteins. PRMTs play a crucial
      role in influencing various cellular functions, including cellular development
      and tumorigenesis. Arginine methylation by PRMTs is found on both nuclear and
      cytoplasmic proteins. Recently, there is increasing evidence regarding post
      translational modifications of non-histone proteins by PRMTs, illustrating the
      previously unknown importance of PRMTs in the regulation of various cellular
      functions by post-translational modifications. In this review, we present the
      recent developments in the regulation of non-histone proteins by PRMTs. 

PMID- 24296624
TI  - Screening: Screening for kidney disease--a lost opportunity.
AB  - The ACP has published 'weak' guidelines for screening patients for kidney disease
      based on limited or no data, which could harm patients with undiagnosed or
      progressive kidney disease. As kidney experts weren't involved in the development
      of these guidelines, what should all health professionals know about screening
      for kidney disease?

PMID- 24296625
TI  - Stem cells: Budding renal progenitors.

PMID- 24296623
TI  - The effect of RAAS blockade on the progression of diabetic nephropathy.
AB  - The renin-angiotensin-aldosterone system (RAAS) has a key role in the regulation
      of blood pressure, sodium and water balance, and cardiovascular and renal
      homeostasis. In diabetic nephropathy, excessive activation of the RAAS results in
      progressive renal damage. RAAS blockade using angiotensin-converting-enzyme
      inhibitors or angiotensin-receptor blockers is the cornerstone of treatment of
      diabetic renal disease. Alternative RAAS-blockade strategies include renin
      inhibition and aldosterone blockade. Data from small initial studies of these
      agents are promising. However, single-agent interventions do not fully block the
      RAAS and patients treated with these therapies remain at high residual renal
      risk. Approaches to optimize drug responses include dietary changes and
      increasing dosages. The theoretically attractive option of combining different
      RAAS interventions has also been tested in clinical trials but long-term outcomes
      were disappointing. However, dual RAAS blockade might represent a good
      therapeutic option for specific patients. A better knowledge of the
      pathophysiology of the RAAS is crucial to fully understand the mechanisms of
      action of RAAS blockers and to exploit their renoprotective effects. Moreover,
      lifestyle interventions or diagnostic tools might be used to optimize RAAS
      blockade and identify those patients who are most likely to benefit from the
      therapy. 

PMID- 24296626
TI  - Genetics in kidney disease in 2013: Susceptibility genes for renal and urological
      disorders.
AB  - In 2013, substantial progress was made in uncovering the genetic basis of a
      variety of kidney and urological disorders, including congenital and
      developmental diseases. The new findings will lead to an increased understanding
      of the pathophysiology of these diseases, improved risk prediction and the
      development of novel therapies.

PMID- 24296627
TI  - Stem cells in 2013: Potential use of stem or progenitor cells for kidney
      regeneration.
AB  - 2013 saw the publication of numerous studies that identified resident renal stem
      or progenitor cells, induced pluripotent stem cells and strategies based on stem
      cell paracrine action, which all might be suitable for kidney regeneration after
      injury.

PMID- 24296628
TI  - Dialysis: Early pre-emptive intervention might reduce AVF access loss.
AB  - American and European vascular access guidelines advise intensive surveillance of
      haemodialysis arteriovenous fistulas (AVFs) with pre-emptive access intervention
      based on deterioration in access flow. The combination of physical examination,
      venous pressure and access flow might provide a better indicator of need for
      intervention and reduce the risk of AVF thrombosis and access loss.

PMID- 24296630
TI  - Two dimensional Dirac carbon allotropes from graphene.
AB  - Using a structural search method in combination with first-principles
      calculations, we found lots of low energy 2D carbon allotropes and examined all
      possible Dirac points around their Fermi levels. Three amazing 2D Dirac carbon
      allotropes have been discovered, named as S-graphene, D-graphene and E-graphene.
      By analyzing the topology correlations among S-, T, net W graphene and graphene,
      we found that a general rule is valuable for constructing 2D carbon allotropes
      that are keen to possess Dirac cones in their electronic structures. Based on
      this rule, we have successfully designed many new 2D carbon allotropes possessing
      Dirac cones. Their energy order can be well described by an Ising-like model, and
      some allotropes are energetically more stable than those recently reported. The
      related electronic structures of these Dirac allotropes are anisotropy
      distinguished from those of graphene. Moreover, the fact that D- and E-graphene
      present Dirac cones suggests that sp hybridization or sp(3) hybridization could
      not suppress the emerging of Dirac features. Our results demonstrate that the
      Dirac cone and carrier linear dispersion is a very common feature in 2D carbon
      allotropes and can exist beyond the limitations of fundamental structure features
      of graphene. 

PMID- 24296629
TI  - Elderly patients with CKD--dilemmas in dialysis therapy and vascular access.
AB  - The population of elderly patients with end-stage renal disease (ESRD) is growing
      rapidly worldwide. The high prevalence of comorbidities, limited life expectancy
      and complex quality of life issues associated with this population pose
      substantial challenges for clinicians in terms of clinical decision-making and
      providing optimal care. The first dilemma encountered in the management of an
      elderly patient with ESRD is deciding whether to initiate renal replacement
      therapy and, if so, selecting the most-suitable dialysis modality. Planning
      vascular access for haemodialysis is associated with additional challenges.
      Several clinical practice guidelines recommend an arteriovenous fistula, rather
      than a central venous catheter or arteriovenous graft, as the preferred access
      for maintenance haemodialysis therapy. However, whether this recommendation is
      applicable to elderly patients with ESRD and a limited life expectancy is
      unclear. Selection and planning of the most appropriate vascular access for an
      elderly patient with ESRD requires careful consideration of several factors and
      ultimately should lead to an improvement in the patient's quality of life. 

PMID- 24296631
TI  - Positive graphene by chemical design: tuning supramolecular strategies for
      functional surfaces.
AB  - A diazonium based-arylation reaction was efficiently used for the covalent
      addition of 4-amino-N,N,N-trimethylbenzene ammonium to stable dispersions of few
      layer graphene (FLG) yielding an innovative FLG platform with positive charges to
      immobilize inorganic polyanions. 

PMID- 24296632
TI  - Dermoscopy of acral melanoma: a multicenter study on behalf of the international
      dermoscopy society.
AB  - BACKGROUND: Most studies on dermoscopy of acral lesions were conducted in Asian
      populations. In this study, we analyzed these features in a predominantly
      Caucasian population. OBJECTIVE: Estimate the prevalence of dermoscopic features
      in acral lesions, and assess their level of agreement between observers. METHODS:
      In this retrospective multicenter study, 167 acral lesions (66 melanomas) were
      evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet
      platform. RESULTS: Parallel furrow pattern, bizarre pattern, and diffuse
      pigmentation with variable shades of brown had the highest prevalence. The
      agreement for lesion patterns between physicians was variable. Agreement was
      dependent on the level of diagnostic difficulty. CONCLUSION: Lesions with a
      diameter >1 cm were more likely to be melanoma. We found as well that a benign
      pattern can be seen in parts of melanomas. For this reason one should evaluate an
      acral lesion for the presence of malignant patterns first.

PMID- 24296633
TI  - Azithromycin in treatment of patients with asthma and C. Pneumoniae infection.
AB  - Chronic C. pneumoniae infection has been suggested as a cause for adult onset of
      asthma. There are data to suggest that infectious organisms, particularly the
      atypical bacteria C. pneumoniae, may be involved in asthma pathogenesis. The
      significance of these organisms is as yet unclear. It is not known whether this
      organism was allowed to persist after an infection, or was present prior to the
      development of asthma. The purpose of this study was to determine whether anti
      chlamydial treatment with azithromycin will improve asthma symptoms and lung
      function in asthmatic patients positive for C. pneumoniae. For this purpose, 20
      patients (mean age 39.8 years) with mild asthma were treated a median of 8 weeks
      with azithromycin 1000 mg once weekly. All patients had C. pneumoniae infection
      detected by Seeplex Multiplex PCR in sputum and positive IgG titre>1:64 and IgA
      titre>1:16 antibodies against C. pneumoniae. Post treatment lung function,
      symptom score (cough, wheezing, dyspnea), morning and evening PEF values and
      beta2-agonist use were compared with baseline values. After 8 weeks of treatment
      with azithromycin there was a significant reduction in symptom score (p<0.001)
      and a significant improvement in lung function FEV1 (p<0.001), morning and
      evening PEF values p<0.05 Wilcoxon matched Pairs test. We also found a reduction
      in beta2-agonist use, but it was not statistically significant. Treatment with
      azithromycin significantly improved asthma symptoms and lung function, indicating
      that C. pneumoniae may play an important role in enhancing the inflammatory
      processes in the lower airways.

PMID- 24296634
TI  - The degree of H19 hypomethylation in children with Silver-Russel syndrome (SRS)
      is not associated with the severity of phenotype and the clinical severity score
      (CSS).
AB  - BACKGROUND: Hypomethylation of the imprinting control region 1 (ICR 1) at the
      IGF2/H19 locus on 11p15 is linked to Silver-Russel syndrome (SRS). METHODS AND
      RESULTS: We tested the hypothesis that the severity of the phenotype in SRS
      patients is dependent on the clinical severity score (CSS) (1). Three SRS
      patients were clinically scored and their scores ranged between 12, 13 and 13.
      Two of the three SRS patients (66%) had hypomethylation of one allele.
      CONCLUSION: All three patients had high CSS. Nevertheless, only two of them had
      hypomethylation of one H19 allele. Interestingly, two of them had ventricular
      septal defects, but only one had H19 hypomethylation. All children had low birth
      length and weight, a classic facial phenotype, haemihypertrophy (>2.5 cm thinner
      left arm/leg in comparison to the right one), shorter leg, and striking thinness
      (BMI of >16.0). One child was operated for cryptorchidismus, and the same child
      had elbow contracture. Two children had scoliosis. All three children were short
      (-3 to 5.5 SD), and treatment with GH resulted in growth on the third percentile.
      Since one child had no hypomethylation and two had a lower degree of
      hypomethylation, the higher CSS (12, 13 and 13) was not followed by a higher
      degree of hypomethylation of the IGF2/H19 locus.

PMID- 24296635
TI  - Obesity in childhood and adolescence, genetic factors.
AB  - Obesity and overweight are a pandemic phenomenon in the modern world. Childhood
      and adolescent obesity often ends up in obesity in adults. The costs of obesity
      and its consequences are staggering for any society, crippling for countries in
      development. The etiology is complex, but most often idiopathic. Hormonal,
      syndromic and medication-induced obesity are well investigated. Genetic causes
      are increasingly described. Novel technologies such as whole exome sequencing
      identify ever more candidate genes influencing or causing obesity. All insights
      into the complex problem of obesity in a team approach to treatment: diet,
      psychology, medications and surgery. We briefly review epidemiology, etiology,
      consequences and treatment approaches in childhood and adolescent obesity, with
      special emphasis on emerging knowledge of its genetics.

PMID- 24296636
TI  - Dermatoglyphics in patients with schizophrenia--findings in the Macedonian
      population.
AB  - The human palms and soles are textured with skin different to that of the other
      body surface. Instead of sebaceous glands or hairs, there are sweat glands
      opening into epidermal ridges. They are variously oriented, thus forming
      different patterns. The aim of the study was to assess some dermatoglyphic
      patterns, the TRC and the a-b ridge count in a sample of patients and a control
      group of healthy examinees. MATERIAL AND METHOD: 59 male and 50 female patients
      with schizophrenia and 60 healthy male and 50 female individuals as a control
      group were included in the study. Hand prints were taken using the method of
      Cummins and Midlo; pattern types were determined and classified using the Henry
      classification. An analysis of pattern frequency in schizophrenia compared to the
      normal controls was conducted. RESULTS: The patterns most frequently present are
      loops (ulnar) with greater incidence and whorls with smaller incidence in
      patients with schizophrenia compared to the healthy individuals. The number of
      arches is higher in male patients and lower in female patients. Complex patterns
      are rare. TRC in females has lower values found in patients. The a-b ridge count
      has significant difference in male and female patients; higher values in male and
      lower in female patients. CONCLUSION: There is some association between the
      frequency of certain dermatoglyphic characteristicss and schizophrenia. Our
      findings form a useful database for the dermatoglyphic marks present in patients
      with schizophrenia and healthy subjects of Macedonian nationality.

PMID- 24296637
TI  - Do women live longer or do men die earlier? Reflections on the causes of sex
      differences in life expectancy.
AB  - BACKGROUND: Although many different factors have been identified to contribute to
      excess male mortality, it is still unclear which path of the complex cause-effect
      chain is the decisive driver of the life expectancy gap between women and men.
      OBJECTIVE: The question behind this study is whether these sex differences are
      caused primarily by factors leading to low female mortality or rather by factors
      causing high male mortality. We hypothesise that they are to a large extent
      caused by specific subpopulations of men with particularly high mortality levels
      that decrease the average life expectancy of men. METHODS: To test this
      hypothesis, we investigate in a meta-analysis the variability in mortality (VM)
      in women and men - defined as the range of death rates prevailing among
      subpopulations - in empirical studies analysing specific phenomena of mortality
      differentials. We used the data of 72 empirical studies, including 146 total
      effects (TE) and 1,718 single effects (SE) for 21 different risk factors.
      RESULTS: In 85% of TE and three quarters of SE the VM was higher in men than in
      women, taking into account men's higher overall mortality. The corresponding
      figures for the direct differences in the VM between women and men are 92 and
      82%, respectively. Cases with higher female VM are rare exceptions and appear in
      particular in the highest age groups. CONCLUSIONS: We find support for our
      hypothesis that the disproportionate high mortality levels of specific male
      subpopulations are the central cause of the current extent of sex differences in
      life expectancy. Thus, public health programmes should be targeted toward these
      disadvantaged subpopulations among men which seem to be related primarily to
      socioeconomic characteristics.

PMID- 24296638
TI  - Ethical considerations in stroke patients.
AB  - PURPOSE OF REVIEW: Medical decision-making in stroke patients can be complex and
      often involves ethical challenges, from the perspective of healthcare providers
      as well as patients and their families. Awareness of these challenges and
      knowledge of current ethical topics in stroke may improve the quality of care
      provided to stroke patients. RECENT FINDINGS: Predictive scores are increasingly
      available to estimate prognosis following stroke, though their usefulness in
      decision-making for individual patients remains unclear. Medical decisions
      requiring a surrogate decision-maker can be challenging; surrogates may also be
      susceptible to systematic biases in their decision-making. Variations in care are
      common and possibly related to under-utilization or over-utilization of
      resources. However, patient preferences may explain some of the variability as
      well. Early mortality may be related to patient and family preferences regarding
      life-sustaining measures rather than the provision of care that is not well
      tolerated or evidence-based. SUMMARY: Ethical challenges are common in the care
      of stroke patients. An effective understanding of these topics is essential for
      clinicians to deliver patient-centered, preference-sensitive care.

PMID- 24296639
TI  - Surgical and endovascular interventions in idiopathic intracranial hypertension.
AB  - PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a potentially
      blinding disease and may require surgical management when maximal medical
      treatment has failed. The purpose of this review is to discuss the current
      literature on surgical and endovascular treatments for IIH. RECENT FINDINGS: The
      most commonly performed surgical treatments for IIH are cerebrospinal fluid
      diversion procedures (e.g. ventriculo- and lumbo-peritoneal shunts) and optic
      nerve sheath fenestration. Controversy still exists about which is the preferred
      initial surgical treatment for IIH. Emerging procedures include venous sinus
      stenting in cases with venous sinus stenosis, and bariatric surgery for weight
      loss. Cranial (suboccipital or subtemporal) decompression was a more popular
      surgical procedure in the past, but can still have a role in selected cases with
      impaired cerebrospinal flow dynamics (e.g. Chiari malformation) or after multiple
      failed conventional surgical procedures. SUMMARY: This review compares and
      contrasts the surgical management options for IIH.

PMID- 24296640
TI  - Interventional treatment of brain ischemia related to intracranial
      cerebrovascular occlusive lesions.
AB  - PURPOSE OF REVIEW: This review discusses the present use of interventional
      transcatheter strategies to treat patients with acute brain ischemia and severe
      stenosis of intracranial large arteries. RECENT FINDINGS: The benefits and risks
      of opening freshly occluded intracranial large arteries in patients with brain
      ischemia depend on the extent of infarction, the location, the mechanism of
      thromboembolism, and the clot burden present, as well as time. Mechanical removal
      of thromboemboli with stent retrievers can quickly and effectively open occluded
      arteries. Aggressive medical treatment is highly effective in stabilizing
      intracranial large artery atherostenotic lesions. SUMMARY: Interventional
      treatment of acute and threatened brain ischemia is a rapidly changing field. New
      devices, new thrombolytic agents, and new antithrombotic agents are continuously
      being introduced and tested. Diagnostic imaging advances are improving the
      ability of clinicians to identify the important features needed to select
      patients optimally. Interventionalists are gaining experience with their new
      tools. Key questions remain including patient selection criteria, use of optimal
      brain and vascular imaging, appropriate devices for recanalization, and the
      concomitant use of intravenous thrombolytics, among others.

PMID- 24296642
TI  - A new family of Ln-radical chains (Ln = Nd, Sm, Gd, Tb and Dy): synthesis,
      structure, and magnetic properties.
AB  - Five new one-dimensional rare earth-nitronyl nitroxide radical complexes
      [Ln(hfac)3(NIT-3BrPhOMe)]n (Ln = Nd (1), Sm (2), Gd (3), Tb (4), Dy (5); hfac =
      hexafluoroacetylacetonate; NIT-3BrPhOMe = 2-(3'-bromo-4'-methoxyl)-4,4,5,5
      tetramethyl-imidazolyl-1-oxyl-3-oxide) have been successfully prepared and
      structurally characterized. Five complexes possess linear chain structure in
      which the NIT-3BrPhOMe radical ligands link Ln(hfac)3 units through the oxygen
      atoms of nitronyl nitroxide groups. DC magnetic studies show that Nd, Sm and Gd
      complexes are paramagnetic above 2.0 K, whereas Tb and Dy complexes show
      antiferromagnetic ordering with T(N) = 19.9 K and 6.4 K, respectively. Moreover,
      Tb and Dy complexes exhibit frequency-dependence of ac magnetic susceptibilities,
      suggesting the presence of slow magnetic relaxation. This work demonstrated that
      the substituents of the nitronyl nitroxide radical and the lanthanide ion can
      play a crucial role in modulating the magnetic behavior for one-dimensional
      lanthanide-radical systems.

PMID- 24296643
TI  - Evolving treatment options in coronary artery disease.

PMID- 24296641
TI  - Transcranial brain stimulation to promote functional recovery after stroke.
AB  - PURPOSE OF REVIEW: Noninvasive brain stimulation (NIBS) is increasingly used to
      enhance the recovery of function after stroke. The purpose of this review is to
      highlight and discuss some unresolved questions that need to be addressed to
      better understand and exploit the potential of NIBS as a therapeutic tool. RECENT
      FINDINGS: Recent meta-analyses showed that the treatment effects of NIBS in
      patients with stroke are rather inconsistent across studies and the evidence for
      therapeutic efficacy is still uncertain. This raises the question of how NIBS can
      be developed further to improve its therapeutic efficacy. SUMMARY: This review
      addressed six questions: How does NIBS facilitate the recovery of function after
      stroke? Which brain regions should be targeted by NIBS? Is there a particularly
      effective NIBS modality that should be used? Does the location of the stroke
      influence the therapeutic response? How often should NIBS be repeated? Is the
      functional state of the brain during or before NIBS relevant to therapeutic
      efficacy of NIBS? We argue that these questions need to be tackled to obtain
      sufficient mechanistic understanding of how NIBS facilitates the recovery of
      function. This knowledge will be critical to fully unfold the therapeutic effects
      of NIBS and will pave the way towards adaptive NIBS protocols, in which NIBS is
      tailored to the individual patient.

PMID- 24296644
TI  - Old, wise and allergic: allergies are no longer solely diseases of the
      grandchildren.

PMID- 24296646
TI  - Hydrogen-bonded complexes upon spatial confinement: structural and energetic
      aspects.
AB  - In the present study we consider structural and energetic aspects of spatial
      confinement of the H-bonded systems. The model dimeric systems: HF...HF,
      HCN...HCN and HCN...HCCH have been chosen for a case study. Two-dimensional
      harmonic oscillator potential, mimicking a cylindrical confinement, was applied
      in order to render the impact of orbital compression on the analyzed molecular
      complexes. The calculations have been performed employing the MP2 method as well
      as the Kohn-Sham formulation of density functional theory. In the latter case,
      two exchange-correlation potentials have been used, namely B3LYP and M06-2X. The
      geometries of studied complexes have been optimized (without any constraints) in
      the presence of the applied model confining potential. A thorough analysis of
      topological parameters characterizing hydrogen bonds upon orbital compression has
      been performed within the Quantum Theory of Atoms in Molecules (QTAIM).
      Furthermore, an energetic analysis performed for the confined H-bonded complexes
      has shown a different trend in the interaction energy changes. Additionally, a
      variational-perturbational decomposition scheme was applied to study the
      interaction energy components in the presence of spatial confinement.

PMID- 24296645
TI  - Tenofovir or zidovudine in second-line antiretroviral therapy after stavudine
      failure in southern Africa.
AB  - BACKGROUND: There is debate over using tenofovir or zidovudine alongside
      lamivudine in second-line antiretroviral therapy (ART) following stavudine
      failure. We analysed outcomes in cohorts from South Africa, Zambia and Zimbabwe
      METHODS: Patients aged >=16 years who switched from a first-line regimen
      including stavudine to a ritonavir-boosted lopinavir-based second-line regimen
      with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART
      programmes in southern Africa were included. We estimated the causal effect of
      receiving tenofovir or zidovudine on mortality and virological failure using Cox
      proportional hazards marginal structural models. Its parameters were estimated
      using inverse probability of treatment weights. Baseline characteristics were
      age, sex, calendar year and country. CD4(+) T-cell count, creatinine and
      haemoglobin levels were included as time-dependent confounders. RESULTS: A total
      of 1,256 patients on second-line ART, including 958 on tenofovir, were analysed.
      Patients on tenofovir were more likely to have switched to second-line ART in
      recent years, spent more time on first-line ART (33 versus 24 months) and had
      lower CD4(+) T-cell counts (172 versus 341 cells/MUl) at initiation of second
      line ART. The adjusted hazard ratio comparing tenofovir with zidovudine was 1.00
      (95% CI 0.59, 1.68) for virological failure and 1.40 (0.57, 3.41) for death.
      CONCLUSIONS: We did not find any difference in treatment outcomes between
      patients on tenofovir or zidovudine; however, the precision of our estimates was
      limited. There is an urgent need for randomized trials to inform second-line ART
      strategies in resource-limited settings.

PMID- 24296647
TI  - Estimation of caries experience by multiple imputation and direct
      standardization.
AB  - Valid estimates of caries experience are needed to monitor oral population
      health. Obtaining such estimates in practice is often complicated by nonresponse
      and missing data. The goal of this study was to estimate caries experiences in a
      population of children aged 5 and 11 years, in the presence of nonresponse and
      missing data. Four estimation methods are compared. Each method makes implicit
      assumptions about the processes that caused the nonresponse and the missing data.
      Three of the four methods are based on unrealistic assumptions about the missing
      data and underestimate caries experience. Under the missing at random assumption,
      multiple imputation in combination with direct standardization corrects for the
      deficiencies of current methodology. In the presence of missing data and
      nonresponse, we recommend a combination of multiple imputation and direct
      standardization to obtain correct estimates of caries experience.

PMID- 24296648
TI  - Unprecedented organocatalytic reduction of lignin model compounds to phenols and
      primary alcohols using hydrosilanes.
AB  - The first metal-free reduction of lignin model compounds is described. Using
      inexpensive Et3SiH, PMHS and TMDS hydrosilanes as reductants, alpha-O-4 and beta
      O-4 linkages are reduced to primary alcohols and phenols under mild conditions
      using B(C6F5)3 as an efficient catalyst. 

PMID- 24296649
TI  - Retroperitoneal, paraspinal migration of distal ventriculoperitoneal shunt
      catheter: a peculiar complication of cerebrospinal fluid shunt.
AB  - We describe a case of a ventriculoperitoneal shunt malfunction in which the tip
      of the peritoneal catheter found its way to the paraspinal subcutaneous tissues.
      The specific findings on physical examination and the results of the imaging made
      to make the diagnosis are presented. No prior report of migrating shunt tubing
      into this anatomic area was found in the literature. This curiosity is added to
      the list of organs or spaces shunts are capable of wandering into.

PMID- 24296651
TI  - Congenital medial dislocation of the patella with multiple congenital anomalies:
      case report and method of treatment.
AB  - Lateral dislocation of the patella is reported frequently in orthopaedics
      references but congenital medial patellar dislocation is reported rarely. An 8
      year-old girl was referred to our department for knee surgery. She had genuvarum,
      knee flexion contracture and tibial internal rotation. She had multiple
      congenital anomalies at birth. The patella was palpated in the medial side of
      knee and its reduction to the midline was impossible. We performed an operative
      procedure for her medial dislocation of the patella. At the 1-year follow-up, the
      patella was in midline and there was no medial subluxation on range of motion of
      the knee. In infants with genuvarum, knee flexion contracture and tibial internal
      rotation, the possibility of medial patellar instability should be considered.
      For correction of patellar tracking and prevention of bone deformities, surgical
      management should be performed.

PMID- 24296650
TI  - Overexpression of KCNN3 results in sudden cardiac death.
AB  - BACKGROUND: A recent genome-wide association study identified a susceptibility
      locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for
      a small conductance calcium-activated potassium channel, we hypothesized that
      overexpression of the SK3 channel increases susceptibility to cardiac
      arrhythmias. METHODS AND RESULTS: We characterized the cardiac
      electrophysiological phenotype of a mouse line with overexpression of the SK3
      channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with
      overexpression of the channel and compared them with wild-type (WT) controls. We
      observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T)
      mice). Ambulatory monitoring demonstrated that sudden death was due to heart
      block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight,
      temperature, and cardiac function on echocardiography; however, histological
      analysis demonstrated that these mice have abnormal atrioventricular node
      morphology. Optical mapping demonstrated that SK3(T/T) mice have slower
      ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 +/- 0.04
      vs. 0.60 +/- 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old
      SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0%
      of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T)
      vs. WT; 43 +/- 6 vs. 52 +/- 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the
      other hand displayed a trend towards a more prolonged atrioventricular nodal
      refractory period (SK3(T/T) vs. WT; 61 +/- 1 vs. 52 +/- 6 ms, P = 0.06).
      CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden
      death associated with bradyarrhythmias and heart block, possibly due to
      atrioventricular nodal dysfunction.

PMID- 24296652
TI  - Triplane fracture of distal radius treated surgically: case report and review of
      the literature.
AB  - Only four cases of triplane distal radius fracture have been described in the
      literature. We report the first that has been treated with open reduction and
      internal fixation. A 15-year-old boy sustained a triplane fracture of the distal
      radius. After an unsuccessful attempt at closed reduction, open reduction and
      internal fixation were performed. Six months after injury, the patient is
      asymptomatic, but radiographs show a partial growth arrest. The goal of treatment
      is to achieve anatomic reduction of the articular surface. In this case
      interposed periosteum prevented anatomic reduction, requiring open reduction and
      internal fixation. Because of the patient's advanced age the partial physeal
      arrest should advance to complete arrest before length impairment or occurrence
      of angular deformity. 

PMID- 24296653
TI  - Prion disease: A newly identified mutation in prion protein is associated with
      diarrhoea and autonomic neuropathy.

PMID- 24296654
TI  - Movement disorders: Tourette syndrome--beyond swearing and sex?

PMID- 24296656
TI  - Parkinson disease: Low vitamin D and Parkinson disease--a causal conundrum.

PMID- 24296657
TI  - Neurometabolic disease: Treating mitochondrial diseases with mTOR inhibitors--a
      potential treatment for Leigh syndrome?

PMID- 24296655
TI  - Primary cilia in neurodevelopmental disorders.
AB  - Primary cilia are generally solitary organelles that emanate from the surface of
      almost all vertebrate cell types. Until recently, details regarding the function
      of these structures were lacking; however, extensive evidence now suggests that
      primary cilia have critical roles in sensing the extracellular environment, and
      in coordinating developmental and homeostatic signalling pathways. Furthermore,
      disruption of these functions seems to underlie a diverse spectrum of disorders,
      known as primary ciliopathies. These disorders are characterized by wide-ranging
      clinical and genetic heterogeneity, but with substantial overlap among distinct
      conditions. Indeed, ciliopathies are associated with a large variety of
      manifestations that often include distinctive neurological findings. Herein, we
      review neurological features associated with primary ciliopathies, highlight
      genotype-phenotype correlations, and discuss potential mechanisms underlying
      these findings. 

PMID- 24296658
TI  - Traumatic brain injury: PET imaging detects amyloid deposits after TBI.

PMID- 24296659
TI  - Highly conductive three-dimensional MnO2-carbon nanotube-graphene-Ni hybrid foam
      as a binder-free supercapacitor electrode.
AB  - Carbon nanotube (CNT)-graphene hybrids grown on porous Ni foam are used as
      substrates to immobilize MnO2 nanoflakes, thus forming three-dimensional (3D)
      MnO2-CNT-graphene-Ni hybrid foam. The as-prepared hybrid materials could be used
      as supercapacitor electrodes directly without any binder and conductive
      additives, and fully maintain the high conductivity and high surface-to-volume
      ratio of CNTs, large pseudocapacitance of MnO2 nanoflakes and high porosity
      provided by the framework of Ni foam. The conductivity of the 3D MnO2-CNT
      graphene-Ni foam is as high as 117 S cm(-1) due to the seamless integration of
      MnO2 nanoflakes, CNTs, graphene and Ni foam among the 3D frameworks, which
      guarantee its low internal resistance (1.25 ohm) when compacted into
      supercapacitor devices. In aqueous electrolytes, the 3D MnO2-CNT-graphene-Ni
      based prototype supercapacitors show specific capacitances of ~251 F g(-1) with
      good cycling stability at a current density of 1.0 A g(-1). In addition, these 3D
      hybrids also demonstrate their potential in all-solid-state flexible
      supercapacitors.

PMID- 24296660
TI  - A novel GHR intronic variant, c.266+83G>T , activates a cryptic 5' splice site
      causing severe GHR deficiency and classical GH insensitivity syndrome.
AB  - BACKGROUND/AIMS: Mutations in the human growth hormone receptor gene (GHR) are
      the most common cause of growth hormone insensitivity (GHI) syndrome and insulin
      like growth factor (IGF-1) deficiency. The extracellular domain of GHR (encoded
      by exons 2-7 of the GHR gene) can be proteolytically cleaved to circulate as GH
      binding protein (GHBP). METHODS: We evaluated the cause of classical GHI (Laron)
      phenotypes in 3 siblings. RESULTS: Two brothers (aged 16.5 and 14.9 years) and
      their half-brother (aged 11.3 years) presented with extreme short stature (height
      standard deviation score, SDS, of -7.05, -6.34 and -8.02, respectively). The
      parents were consanguineous and of normal stature. Serum GHBP levels of probands
      were undetectable and circulating IGF-1 and IGF-binding protein-3 were abnormally
      low, but GH concentrations were elevated. Molecular analysis of the GHR gene
      revealed homozygous deletion of exon 3, a common polymorphism, and a novel
      c.266+83G>T variant within intron 4 which generated a 5' donor splice site.
      Splicing events from this cryptic 5' donor site resulted in retention of 81
      intronic nucleotides in the GHR mRNA. Long-term rhIGF-1 therapy combined with
      leuprolide depot increased height by +2 to +3 SDS. CONCLUSION: The c.266+83G>T is
      the second intronic GHR mutation identified that activates a cryptic 5' donor
      splice site. The abnormal splicing event led to early protein termination and
      undetectable serum GHBP concentrations. (c) 2013 S. Karger AG, Basel.

PMID- 24296661
TI  - Two evolutionarily distinct classes of paleopolyploidy.
AB  - Whole genome duplications (WGDs) occurred in the distant evolutionary history of
      many lineages and are particularly frequent in the flowering plant lineages.
      Following paleopolyploidization in plants, most duplicated genes are deleted by
      intrachromosomal recombination, a process referred to as fractionation. In the
      examples studied so far, genes are disproportionately lost from one of the
      parental subgenomes (biased fractionation) and the subgenome having lost the
      lowest number of genes is more expressed (genome dominance). In the present
      study, we analyzed the pattern of gene deletion and gene expression following the
      most recent WGD in banana (alpha event) and extended our analyses to seven other
      sequenced plant genomes: poplar, soybean, medicago, arabidopsis, sorghum,
      brassica, and maize. We propose a new class of ancient WGD, with Musa (alpha),
      poplar, and soybean as members, where genes are both deleted and expressed to an
      equal extent (unbiased fractionation and genome equivalence). We suggest that
      WGDs with genome dominance and biased fractionation (Class I) may result from
      ancient allotetraploidies, while WGDs without genome dominance or biased
      fractionation (Class II) may result from ancient autotetraploidies. 

PMID- 24296662
TI  - Distribution of conventional and nonconventional introns in tubulin (alpha and
      beta) genes of euglenids.
AB  - The nuclear genomes of euglenids contain three types of introns: conventional
      spliceosomal introns, nonconventional introns for which a splicing mechanism is
      unknown (variable noncanonical borders, RNA secondary structure bringing together
      intron ends), and so-called intermediate introns, which combine features of
      conventional and nonconventional introns. Analysis of two genes, tubA and tubB,
      from 20 species of euglenids reveals contrasting distribution patterns of
      conventional and nonconventional introns--positions of conventional introns are
      conserved, whereas those of the nonconventional ones are unique to individual
      species or small groups of closely related taxa. Moreover, in the group of
      phototrophic euglenids, 11 events of conventional intron loss versus 15 events of
      nonconventional intron gain were identified. A comparison of all nonconventional
      intron sequences highlighted the most conserved elements in their sequence and
      secondary structure. Our results led us to put forward two hypotheses. 1) The
      first one posits that mutational changes in intron sequence could lead to a
      change in their excision mechanism--intermediate introns would then be a
      transitional form between the conventional and nonconventional introns. 2) The
      second hypothesis concerns the origin of nonconventional introns--because of the
      presence of inverted repeats near their ends, insertion of MITE-like transposon
      elements is proposed as a possible source of new introns.

PMID- 24296665
TI  - Presentation of mantle cell lymphoma with symptoms of prostatism.

PMID- 24296663
TI  - Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and
      low density lipoprotein uptake.
AB  - Dysregulation of cholesterol homeostasis is associated with various metabolic
      diseases, including atherosclerosis and type 2 diabetes. The sterol response
      element binding protein (SREBP)-2 transcription factor induces the expression of
      genes involved in de novo cholesterol biosynthesis and low density lipoprotein
      (LDL) uptake, thus it plays a crucial role in maintaining cholesterol
      homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells
      repressed SREBP-2 expression and protein level. miR-185-directed inhibition
      caused decreased SREBP-2-dependent gene expression, LDL uptake, and HMG-CoA
      reductase activity. In addition, we found that miR-185 expression was tightly
      regulated by SREBP-1c, through its binding to a single sterol response element in
      the miR-185 promoter. Moreover, we found that miR-185 expression levels were
      elevated in mice fed a high-fat diet, and this increase correlated with an
      increase in total cholesterol level and a decrease in SREBP-2 expression and
      protein. Finally, we found that individuals with high cholesterol had a 5-fold
      increase in serum miR-185 expression compared with control individuals. Thus, miR
      185 controls cholesterol homeostasis through regulating SREBP-2 expression and
      activity. In turn, SREBP-1c regulates miR-185 expression through a complex
      cholesterol-responsive feedback loop. Thus, a novel axis regulating cholesterol
      homeostasis exists that exploits miR-185-dependent regulation of SREBP-2 and
      requires SREBP-1c for function. 

PMID- 24296664
TI  - Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV
      589 fibroblasts.
AB  - Secreted PCSK9 binds to cell surface LDL receptor (LDLR) and directs the receptor
      for lysosomal degradation. PCSK9 is potent at inducing LDLR degradation in
      cultured liver-derived cells, but it is considerably less active in immortalized
      fibroblasts. We examined PCSK9 trafficking in SV-589 human skin fibroblasts
      incubated with purified recombinant wild-type PCSK9 or gain-of-function mutant
      PCSK9-D374Y with increased LDLR binding affinity. Despite LDLR-dependent PCSK9
      uptake, cell surface LDLR levels in SV-589 fibroblasts were only modestly reduced
      by wild-type PCSK9, even at high nonphysiological concentrations (20 ug/ml).
      Internalized (125)I-labeled wild-type PCSK9 underwent lysosomal degradation at
      high levels, indicating its dissociation from recycling LDLRs. PCSK9-D374Y (2
      ug/ml) reduced cell surface LDLRs by approximately 50%, but this effect was still
      blunted compared with HepG2 hepatoma cells. Radioiodinated PCSK9-D374Y was
      degraded less efficiently in SV-589 fibroblasts, and Alexa488-labeled PCSK9-D374Y
      trafficked to both lysosomes and endocytic recycling compartments. Endocytic
      recycling assays showed that more than 50% of internalized PCSK9-D374Y recycled
      to the cell surface compared with less than 10% for wild-type PCSK9. These data
      support that wild-type PCSK9 readily dissociates from the LDLR within early
      endosomes of SV-589 fibroblasts, contributing to PCSK9-resistance. Although a
      large proportion of gain-of-function PCSK9-D374Y remains bound to LDLR in these
      cells, degradative activity is still diminished. 

PMID- 24296666
TI  - Migration of the ventriculoperitoneal shunt presenting as a breast lump.

PMID- 24296667
TI  - First report of the genetic background of Marfan syndrome in Polish patients.

PMID- 24296668
TI  - Response to metronidazole and oxidative stress is mediated through homeostatic
      regulator HsrA (HP1043) in Helicobacter pylori.
AB  - Metronidazole (MTZ) is often used in combination therapies to treat infections
      caused by the gastric pathogen Helicobacter pylori. Resistance to MTZ results
      from loss-of-function mutations in genes encoding RdxA and FrxA nitroreductases.
      MTZ-resistant strains, when cultured at sub-MICs of MTZ (5 to 20 MUg/ml), show
      dose-dependent defects in bacterial growth; depressed activities of many Krebs
      cycle enzymes, including pyruvate:ferredoxin oxidoreductase (PFOR); and low
      transcript levels of porGDAB (primer extension), phenotypes consistent with an
      involvement of a transcriptional regulator. Using a combination of protein
      purification steps, electrophoretic mobility shift assays (EMSAs), and mass
      spectrometry analyses of proteins bound to porG promoter sequences, we identified
      HP1043, an essential homeostatic global regulator (HsrA [for homeostatic stress
      regulator]). Competition EMSAs and supershift analyses with HsrA-enriched protein
      fractions confirmed specific binding to porGDAB and hsrA promoter sequences.
      Exposure to MTZ resulted in >10-fold decreases in levels of HsrA and in levels of
      the HsrA-regulated gene products PFOR and TlpB. Exposure to paraquat (PQ),
      hydrogen peroxide, or organic peroxides showed near equivalence with MTZ,
      revealing a common oxidative stress response pathway. Finally, direct superoxide
      dismutase (SOD) assays showed an inverse relationship between HsrA levels and SOD
      activity, suggesting that HsrA may serve as a repressor of sodB. As a homeostatic
      sentinel, HsrA appears to be ideally positioned to enable rapid shutdown of genes
      associated with metabolism and growth while activating (directly or indirectly)
      oxidative defense genes in response to low levels of toxic metabolites (MTZ or
      oxygen) before they reach DNA-damaging levels. 

PMID- 24296670
TI  - The MiaA tRNA modification enzyme is necessary for robust RpoS expression in
      Escherichia coli.
AB  - The stationary phase/general stress response sigma factor RpoS (sigma(S)) is
      necessary for adaptation and restoration of homeostasis in stationary phase. As a
      physiological consequence, its levels are tightly regulated at least at two
      levels. Multiple small regulatory RNA molecules modulate its translation, in a
      manner that is dependent on the RNA chaperone Hfq and the rpoS 5' untranslated
      region. ClpXP and the RssB adaptor protein degrade RpoS, unless it is protected
      by an anti-adaptor. We here find that, in addition to these posttranscriptional
      levels of regulation, tRNA modification also affects the steady-state levels of
      RpoS. We screened mutants of several RNA modification enzymes for an effect on
      RpoS expression and identified the miaA gene, encoding a tRNA
      isopentenyltransferase, as necessary for full expression of both an rpoS750-lacZ
      translational fusion and the RpoS protein. This effect is independent of rpoS,
      the regulatory RNAs, and RpoS degradation. RpoD steady-state levels were not
      significantly different in the absence of MiaA, suggesting that this is an RpoS
      specific effect. The rpoS coding sequence is significantly enriched for leu
      codons that use MiaA-modified tRNAs, compared to rpoD and many other genes.
      Dependence on MiaA may therefore provide yet another way for RpoS levels to
      respond to growth conditions. 

PMID- 24296669
TI  - Defects in the flagellar motor increase synthesis of poly-gamma-glutamate in
      Bacillus subtilis.
AB  - Bacillus subtilis swims in liquid media and swarms over solid surfaces, and it
      encodes two sets of flagellar stator homologs. Here, we show that B. subtilis
      requires only the MotA/MotB stator during swarming motility and that the residues
      required for stator force generation are highly conserved from the Proteobacteria
      to the Firmicutes. We further find that mutants that abolish stator function also
      result in an overproduction of the extracellular polymer poly-gamma-glutamate
      (PGA) to confer a mucoid colony phenotype. PGA overproduction appeared to be the
      result of an increase in the expression of the pgs operon that encodes genes for
      PGA synthesis. Transposon mutagenesis was conducted to identify insertions that
      abolished colony mucoidy and disruptions in known transcriptional regulators of
      PGA synthesis (Com and Deg two-component systems) as well as mutants defective in
      transcription-coupled DNA repair (Mfd)-reduced expression of the pgs operon. A
      final class of insertions disrupted proteins involved in the assembly of the
      flagellar filament (FliD, FliT, and FlgL), and these mutants did not reduce
      expression of the pgs operon, suggesting a second mechanism of PGA control. 

PMID- 24296671
TI  - The integron integrase efficiently prevents the melting effect of Escherichia
      coli single-stranded DNA-binding protein on folded attC sites.
AB  - Integrons play a major role in the dissemination of antibiotic resistance genes
      among bacteria. Rearrangement of gene cassettes occurs by recombination between
      attI and attC sites, catalyzed by the integron integrase. Integron recombination
      uses an unconventional mechanism involving a folded single-stranded attC site.
      This site could be a target for several host factors and more precisely for
      proteins able to bind single-stranded DNA. One of these, Escherichia coli single
      stranded DNA-binding protein (SSB), regulates many DNA processes. We studied the
      influence of this protein on integron recombination. Our results show the ability
      of SSB to strongly bind folded attC sites and to destabilize them. This effect
      was observed only in the absence of the integrase. Indeed, we provided evidence
      that the integrase is able to counterbalance the observed effect of SSB on attC
      site folding. We showed that IntI1 possesses an intrinsic property to capture
      attC sites at the moment of their extrusion, stabilizing them and recombining
      them efficiently. The stability of DNA secondary structures in the chromosome
      must be restrained to avoid genetic instability (mutations or deletions) and/or
      toxicity (replication arrest). SSB, which hampers attC site folding in the
      absence of the integrase, likely plays an important role in maintaining the
      integrity and thus the recombinogenic functionality of the integron attC sites.
      We also tested the RecA host factor and excluded any role of this protein in
      integron recombination. 

PMID- 24296672
TI  - Amino-4-imidazolecarboxamide ribotide directly inhibits coenzyme A biosynthesis
      in Salmonella enterica.
AB  - Aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate
      and a by-product of histidine biosynthesis. In bacteria, yeast, and humans,
      accumulation of AICAR has been shown to affect an array of cellular processes by
      both direct and indirect mechanisms. In purine biosynthesis, AICAR is the
      substrate of the bifunctional protein phosphoribosylaminoimidazolecarboxamide
      formyltransferase/IMP cyclohydrolase (PurH, EC 2.1.2.3/3.5.4.10). Strains lacking
      PurH accumulate AICAR and have a defect in the synthesis of the 4-amino-5
      hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine. The formation of HMP
      is also compromised in vivo when coenzyme A (CoA) levels are reduced. Our results
      show that the in vivo accumulation of AICAR decreased total CoA pools and,
      further, that AICAR inhibited the activity of pantoate beta-alanine ligase in
      vitro (PanC, EC 6.3.2.1). These results demonstrated a mechanism of AICAR action
      and provide new insights into the metabolic consequences of disrupting purine
      metabolism. 

PMID- 24296674
TI  - Presence of anti-interferon antibodies is not associated with non-response to
      pegylated interferon treatment in chronic hepatitis B.
AB  - BACKGROUND: Several factors have been related to response to pegylated interferon
      (PEG-IFN) in chronic hepatitis B (CHB). The occurrence of anti-IFN antibodies is
      associated with non-response to PEG-IFN in chronic hepatitis C. This study
      investigated the association between anti-IFN antibodies and response to PEG-IFN
      in CHB. METHODS: Presence of anti-IFN antibodies was assessed at baseline and at
      3 and 6 months post-treatment in 323 CHB patients treated with PEG-IFN for 1
      year. RESULTS: At baseline, anti-IFN antibodies were detected in 112 (35%)
      patients. Prevalence was higher in HBeAg-negative compared to HBeAg-positive CHB
      (43% versus 31%, respectively; P=0.03). Detection of anti-IFN antibodies was not
      associated with age, sex or HBV genotype. Presence of anti-IFN antibodies at
      baseline was associated with previous IFN therapy failure (P=0.04), which
      remained after adjustment for HBeAg status (OR 2.0, 95% CI 1.1, 3.7; P=0.03).
      Presence of anti-IFN antibodies at baseline was not associated with response, nor
      with HBV DNA or HBsAg decline (all P-values>0.3). Overall, 56 of 211 (27%)
      patients without anti-IFN at baseline developed anti-IFN antibodies after PEG-IFN
      treatment. Response rates did not differ between patients who developed anti-IFN
      antibodies and patients who did not develop anti-IFN antibodies during treatment
      (P=0.1). CONCLUSIONS: Anti-IFN antibodies may frequently be detected in CHB
      patients, and presence is associated with previous IFN therapy. However, presence
      or development of anti-IFN antibodies after PEG-IFN therapy is not associated
      with non-response to PEG-IFN treatment in CHB. There appears to be no future role
      for anti-IFN antibodies in predicting response to PEG-IFN in CHB.

PMID- 24296673
TI  - Ght protein of Neisseria meningitidis is involved in the regulation of
      lipopolysaccharide biosynthesis.
AB  - Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram
      negative bacteria and is responsible for the barrier function of this membrane. A
      ght mutant of Neisseria meningitidis that showed increased sensitivity to
      hydrophobic toxic compounds, suggesting a breach in this permeability barrier,
      was previously described. Here, we assessed whether this phenotype was possibly
      caused by a defect in LPS transport or synthesis. The total amount of LPS
      appeared to be drastically reduced in a ght mutant, but the residual LPS was
      still detected at the cell surface, suggesting that LPS transport was not
      impaired. The ght mutant was rapidly overgrown by pseudorevertants that produced
      normal levels of LPS. Genetic analysis of these pseudorevertants revealed that
      the lpxC gene, which encodes a key enzyme in LPS synthesis, was fused to the
      promoter of the upstream-located pilE gene, resulting in severe lpxC
      overexpression. Analysis of phoA and lacZ gene fusions indicated that Ght is an
      inner membrane protein with an N-terminal membrane anchor and its bulk located in
      the cytoplasm, where it could potentially interact with LpxC. Cell fractionation
      experiments indeed indicated that Ght tethers LpxC to the membrane. We suggest
      that Ght regulates LPS biosynthesis by affecting the activity of LpxC. Possibly,
      this mechanism acts in the previously observed feedback inhibition of LPS
      synthesis that occurs when LPS transport is hampered. 

PMID- 24296675
TI  - Dynamics of renal electrolyte excretion in growing mice.
AB  - Genetically modified mice represent important models for elucidating renal
      pathophysiology, but gene deletions frequently cause severe failure to thrive. In
      such cases, the analysis of the phenotype is often limited to the first weeks of
      life when renal excretory function undergoes dramatic physiological changes.
      Here, we investigated the postnatal dynamics of urinary ion excretion in mice.
      The profiles of urinary electrolyte excretion of mice were examined from birth
      until after weaning using an automated ion chromatography system. Postnatally,
      mice grew about 0.4 g/day, except during two phases with slower weight gain: (i)
      directly after birth during adaptation to extrauterine conditions (P0-P2) and
      (ii) during the weaning period (P15-P21), when nutrition changed from mother's
      milk to solid chow and water. During the first 3 days after birth, remarkable
      changes in urinary Na(+), Ca(2+), Mg(2+), and phosphate concentrations occurred,
      whereas K(+) and Cl(-) concentrations hardly changed. From days 4-14 after birth,
      Na(+), Ca(2+), Mg(2+), K(+), and Cl(-) concentrations remained relatively stable
      at low levels. Urinary concentrations of creatinine, NH4(+), phosphate, and
      sulfate constantly increased from birth until after weaning. Profiles of salt
      excretion in KCNJ10(-/-) mice exemplified the relevance of age-dependent analysis
      of urinary excretion. In conclusion, the most critical phases for analysis of
      renal ion excretion during the first weeks of life are directly after birth and
      during the weaning period. The age dependence of urinary excretion varies for the
      different ions. This should be taken into consideration when the renal phenotype
      of mice is investigated during the first weeks of life.

PMID- 24296676
TI  - Osteoarthritis: Lack of Nfatc1 and Nfatc2: a new mouse model of OA.

PMID- 24296677
TI  - Mechanisms and assessment of IgG4-related disease: lessons for the
      rheumatologist.
AB  - Recognition of IgG4-related disease as an independent chronic inflammatory
      disorder is a relatively new concept; previously, the condition was thought to
      represent a subtype of Sjogren's syndrome. IgG4-related disease is characterized
      by elevated serum levels of IgG4 and inflammation of various organs, with
      abundant infiltration of IgG4-bearing plasma cells, storiform fibrosis and
      obliterative phlebitis representing the major histopathological features of the
      swollen organs. The aetiology and pathogenesis of this disorder remain unclear,
      but inflammation and subsequent fibrosis occur due to excess production of type 2
      T-helper-cell and regulatory T-cell cytokines. The disease can comprise various
      organ manifestations, such as dacryoadenitis and sialadenitis (also called
      Mikulicz disease), type 1 autoimmune pancreatitis, kidney dysfunction and lung
      disease. Early intervention using glucocorticoids can improve IgG4-related organ
      dysfunction; however, patients often relapse when doses of these agents are
      tapered. The disease has also been associated with an increased incidence of
      certain malignancies. Increased awareness of IgG4-related disease might lead to
      consultation with rheumatologists owing to its clinical, and potentially
      pathogenetic, similarities with certain rheumatic disorders. With this in mind,
      we describe the pathogenic mechanisms of IgG4-related disease, and outline
      considerations for diagnosis and treatment of the condition. 

PMID- 24296678
TI  - Autoantibodies and SLE: the threshold for disease.
AB  - The presence of autoantibodies in apparently healthy individuals has been
      increasingly recognized. Although some of these individuals are in preclinical
      stages of a disease such as systemic lupus erythematosus (SLE), many will not
      develop SLE or any other autoimmune disorder. The high prevalence of
      autoreactivity in the population in fact suggests that autoantibodies are
      expressed as part of a healthy immune response, and other data have clearly shown
      that some autoantibodies have important immune regulatory functions. These
      observations leave open questions regarding when and how benign autoimmunity
      develops into disease. If the transition from preclinical autoimmunity to a
      clinical disorder such as SLE could be predicted, early and thus potentially more
      effective intervention might be possible and cures might even become a reality.
      Furthermore, increased understanding of mechanisms by which autoantibodies are
      kept in check can identify new approaches to aborting or preventing disease
      transformations. In this article, we summarize the current findings regarding the
      presence of SLE-associated antibodies in apparently healthy individuals, and
      provide our opinions on what such discoveries might tell us about the roles of
      autoantibodies in the development of disease.

PMID- 24296679
TI  - Rheumatoid arthritis: New EULAR guidelines for RA: a job well done.

PMID- 24296680
TI  - Bone diseases: Sclerostin neutralization--a viable pathway for OPPG?

PMID- 24296681
TI  - Strain-induced matrix-dependent deformation of GaAs nanoparticles.
AB  - The influence of compressive strain on the deformation of GaAs nanoparticles
      embedded in different host matrices is investigated. The simulation results
      indicate that it can be easier to deform GaAs nanoparticles grown in an Al2O3
      film than those in an SiO2 film. The deformation induced by the applied
      compressive strain has significant influence on the shape, size and
      microstructure of GaAs nanoparticles. Most significantly, these simulated results
      have a good agreement with HRTEM experimental results. 

PMID- 24296682
TI  - Marked enhancement in electron-hole separation achieved in the low bias region
      using electrochemically prepared Mo-doped BiVO4 photoanodes.
AB  - Mo-doped BiVO4 electrodes were prepared by an electrochemical route for use as
      photoanodes in a photoelectrochemical cell. The purpose of Mo-doping was to
      improve the electron transport properties, which in turn can increase the
      electron-hole separation yield. The poor electron-hole separation yield was known
      to be one of the main limiting factors for BiVO4-based photoanodes. The
      electrochemical route provided an effective way of doping BiVO4, and the
      optimally doped sample, BiV(0.97)Mo(0.03)O4, increased the electron-hole
      separation yield from 0.23 to 0.57 at 0.6 V vs. RHE, which is a record high
      separation yield achieved for BiVO4-based photoanodes. As a result,
      BiV(0.97)Mo(0.03)O4 generated impressive photocurrents, for example, 2 mA cm(-2)
      at a potential as low as 0.4 V vs. RHE for sulfite oxidation, which has fast
      oxidation kinetics and, therefore, the loss of holes by surface recombination is
      negligible. For photooxidation of water, BiV(0.97)Mo(0.03)O4 was paired with
      FeOOH as an oxygen evolution catalyst (OEC) to improve the poor catalytic ability
      of BiV(0.97)Mo(0.03)O4 for water oxidation. The resulting
      BiV(0.97)Mo(0.03)O4/FeOOH photoanodes generated a significantly improved
      photocurrent for water oxidation compared to previous reported results, but the
      photocurrent of BiV(0.97)Mo(0.03)O4/FeOOH for water oxidation could not reach the
      photocurrent of BiV(0.97)Mo(0.03)O4 for sulfite oxidation. In order to examine
      the cause, the effects of Mo-doping on the interaction between BiVO4 and FeOOH
      and the effects of FeOOH on the electron-hole separation yield of
      BiV(0.97)Mo(0.03)O4 were investigated in detail, which provided new insights into
      semiconductor-OEC interactions.

PMID- 24296683
TI  - Self-assembly of a [Ni8] carbonate cube incorporating four MU4-carbonato linkers
      through fixation of atmospheric CO2 by ligated [Ni2] complexes.
AB  - The communication reports the synthesis, characterization, and magnetic behavior
      of a novel MU4-carbonato supported and imidazole capped ligated nickel cage
      [Ni8(MU-H2bpmp)4(MU4-CO3)4(ImH)8](NO3)4.2H2O (1) through self-assembly of ligand
      bound ferromagnetic Ni2 building blocks. Structural analysis indicates newer
      geometrical features for the coordination cage formation and dominant interdimer
      antiferromagnetic coupling resulting in a diamagnetic ground state.

PMID- 24296684
TI  - Per capita sugar consumption in Switzerland is not extreme.

PMID- 24296685
TI  - Noninvasive prenatal testing for whole fetal chromosomal aneuploidies: a
      multicenter prospective cohort trial in Taiwan.
AB  - OBJECTIVE: To evaluate the performance of noninvasive prenatal testing for all
      fetal chromosomal aneuploidies in an extremely high-risk group undergoing first
      trimester combined Down syndrome screening. METHOD: A multicenter cohort
      prospective study in Taiwan was performed between June and December 2012.
      Maternal plasma was collected and shotgun massive parallel sequencing was
      performed on each fetal chromosome. 201 Taiwanese pregnant women at >12 weeks'
      gestation from 11 medical centers were enrolled in this trial. The extremely high
      risk group was defined as a Down syndrome risk cutoff >1:30 or nuchal
      translucency >3.0 mm (n = 100), while the low-risk group was defined as a Down
      syndrome cutoff <1:1,500 (n = 101). Amniocentesis confirmation was performed and
      birth outcome was also recorded. RESULTS: There were 11 cases of trisomy 21, 8
      cases of trisomy 18, 3 cases of trisomy 13, 1 case of trisomy 16, 3 cases of
      45,X, and 1 case of 47,XYY detected prenatally in 100 extremely high-risk
      gravidas [n = 27/100 (27%)]. The overall autosomal or sex chromosome aneuploidy
      detection rate was 96% (27/28) because of an insufficient amount maternal plasma
      for one fetus with Turner syndrome. In the low-risk group, no chromosomal
      abnormalities were detected (specificity = 100%). There were no false-positive
      cases in this study. CONCLUSIONS: This first trial in Taiwan shows that
      noninvasive prenatal testing for whole chromosome aneuploidies can be efficiently
      applied in extremely high- and low-risk populations.

PMID- 24296686
TI  - Availability of consumer prices from Philadelphia area hospitals for common
      services: electrocardiograms vs parking.

PMID- 24296687
TI  - The role of small airway disease in asthma.
AB  - PURPOSE OF REVIEW: This review provides an update on the importance of the
      peripheral 'small' airways in asthma. As the small airways account for less than
      10% of total airway resistance, thus having little impact on standard lung
      function measures such as forced expiratory volume and peak flow, they have been
      referred to as the 'silent zone'. RECENT FINDINGS: The study has revealed that
      small airway involvement is present in all stages of asthmatic disease, being
      related to important clinical phenotypes such as nocturnal asthma, exercise
      induced asthma, and difficult-to-control asthma, including those with the risk of
      repeated asthma exacerbations. Uncontrolled small airway inflammation is related
      to airway remodeling and progression of the disease, with a more rapid decline in
      the lung function. Moreover, studies on both children and adults have shown that
      the involvement of the small airways represents a crucial step in asthma
      development. New tools have been developed and old tools have been refined,
      providing an opportunity to better understand small airway inflammation and
      dysfunction. SUMMARY: Small airway inflammation is present in all stages of
      asthmatic disease and plays an important role in many key clinical
      conditions/phenotypes. In order to control the disease, we need to target small
      airway inflammation, which is not only difficult to reach by standard inhaled
      medications but also to some extent different. A better understanding of the
      important role small airways are playing in asthma will show that the 'silent
      zone' is by far not silent at all.

PMID- 24296688
TI  - An update on allergen immunotherapy and asthma.
AB  - PURPOSE OF REVIEW: The aim is to review recent literature up to July 2013
      concerning the effect of allergen-specific immunotherapy (AIT) on asthma. AIT,
      effective in combined allergic rhinitis and asthma, was previously described as a
      convenient approach able to improve clinical outcomes and reduce bronchial
      hyperresponsiveness. In addition, long-term and preventive effects on the onset
      of new sensitizations and progression from allergic rhinitis to asthma have been
      shown. RECENT FINDINGS: Recent investigations, mainly based on observational or
      small open trials, confirmed previous findings, showing improvement in asthma
      control, symptoms and medication usage and steroid-sparing effects, sometimes
      inconsistent with changes in lung function. Some meta-analyses support the
      clinical benefit on adult and paediatric asthma. Only few trials, however, were
      specifically designed to explore asthma endpoints. SUMMARY: Clinical studies
      primarily have focused on AIT, and research on asthma endpoints is scarce;
      however, the evidence of beneficial effect of AIT for the treatment of adults and
      children affected by allergic rhinitis with or without asthma suggests that this
      treatment can favourably affect asthma. In children, sublingual AIT has been more
      extensively investigated than injective. Confirmatory, adequately powered trials
      are needed to reinforce the evidence of efficacy for individual AIT products. The
      main drawback in using injective AIT for asthma is the risk of serious adverse
      reactions and uncontrolled asthma. The sublingual route is better tolerated and
      does not appear inferior. As standard controller pharmacotherapy seems unable to
      affect the natural course of asthma, the potentially disease-modifying effect of
      AIT represents an appealing perspective that requires further investigation.

PMID- 24296689
TI  - Synthesis and properties of B,N-bridged p-terphenyls.
AB  - The efficient synthesis has been described to achieve a new class of ladder pi
      conjugated molecules, B,N-bridged p-terphenyls. The bridging B atom exhibits a
      more significant effect than the bridging N atom on photophysical properties. 

PMID- 24296691
TI  - Contribution of polyclonal free light chain deposition to tubular injury.
AB  - INTRODUCTION: Excretion of monoclonal free light chains (MFLC) beyond the renal
      threshold can cause kidney injury, but evidence for polyclonal free light chains
      (PFLC)-mediated injury is limited. We aimed to study the degree of PFLC
      deposition in the proximal tubules of chronic kidney disease (CKD) and
      hypothesized that excess deposition may contribute to tubular injury. METHODS: In
      this retrospective study, immunohistochemical staining to assess the degree of
      FLC deposition, periodic acid-Schiff staining for the degree of tubular brush
      border injury and trichrome staining for interstitial fibrosis were evaluated.
      Normal renal parenchyma from tumor nephrectomy specimens (control group I, n =
      39), minimal change disease controls (group II, n = 13), renal biopsies from CKD
      and proteinuria (polyclonal study group III, n = 33) and monoclonal light chain
      nephropathy (group IV, n = 37) were studied. The results of the study including
      serum creatinine were compared between groups. RESULTS: Both polyclonal and
      monoclonal groups (groups III and IV) had significantly higher light chain
      deposition and brush border injury by periodic acid-Schiff scores compared to
      control groups (groups I and II). When the first three polyclonal groups (groups
      I-III) were analyzed together, polyclonal light chain deposition was
      significantly correlated with serum creatinine levels, brush border injury and
      interstitial fibrosis. CONCLUSION: The results of our study suggest that in CKD
      patients with proteinuria, excess PFLC deposition in the proximal tubules may
      cause acute tubular injury akin to monoclonal gammopathy and lead to renal
      chronicity.

PMID- 24296692
TI  - Significance of foamy histiocytes in cervical smears from postmenopausal women.
AB  - OBJECTIVE: To determine the significance of the presence of foamy histiocytes
      (FH) in postmenopausal cervicovaginal smears for the detection of endometrial
      carcinomas (EC). STUDY DESIGN: Endometrial sampling was performed over 6 months
      in 53 of 102 cases that presented with postmenopausal FH, benign endometrial
      cells (BEC), FH with BEC (FH + BEC), and atypical endometrial cells (AEC),
      resulting in a total of 41,150 cervicovaginal smears. The control group consisted
      of 58 cases with a cytologic diagnosis of a normal smear (NS). RESULTS: There
      were 0 (0%), 1 (4.54%), 2 (13.33%), 2 (33.33%), and 5 (50.00%) cases of EC
      diagnosed on histopathologic evaluation in patients with NS (n = 58), BEC (n =
      22), FH (n = 15), FH + BEC (n = 6), and AEC (n = 10), respectively. The
      sensitivities and specificities of the cytologic diagnoses of FH, FH + BEC, and
      AEC for the detection of EC were 81.7 and 100%, 93.6 and 100%, and 92.1 and 100%,
      respectively. CONCLUSION: The cytologic diagnoses of FH and FH + BEC had
      reasonably high sensitivities and specificities for the diagnosis of EC by
      cervicovaginal smear. Additional studies are needed.

PMID- 24296690
TI  - The human IgE repertoire.
AB  - IgE is a key mediator in allergic diseases. However, in strong contrast to other
      antibody isotypes, many details of the composition of the human IgE repertoire
      are poorly defined. The low levels of human IgE in the circulation and the rarity
      of IgE-producing B cells are important reasons for this lack of knowledge. In
      this review, we summarize the current knowledge on these repertoires both in
      terms of their complexity and activity, i.e. knowledge which despite the
      difficulties encountered when studying the molecular details of human IgE has
      been acquired in recent years. We also take a look at likely future developments,
      for instance through improvements in sequencing technology and methodology that
      allow the isolation of additional allergen-specific human antibodies mimicking
      IgE, as this certainly will support our understanding of human IgE in the context
      of human disease in the years to come.

PMID- 24296693
TI  - Achalasia--balloon dilation or surgery?
AB  - BACKGROUND: The optimal therapeutic schedule in patients with achalasia is still
      under discussion. The aim of this study was to review our institution's
      experience with myotomy and dilation in patients with achalasia. MATERIAL AND
      METHODS: Clinical data were available for 59 patients who had ever had myotomy
      (n=38), dilation (n=21), or both procedures (n=8) between 2000 and 2007. Patients
      were followed prospectively with objective (a barium esophagogram) and subjective
      (a simple survey that scored dysphagia and overall patient satisfaction with the
      procedure) diagnostic tools. In the group of patients after pneumatic
      dilatations, frequency of interventions was higher (1, 2) than in the myotomy
      group (0, 2) at 2-year follow-up. Patients after myotomy with recurrence of
      dysphagia were treated with dilations. RESULTS: Mean time of dysphagia occurrence
      was similar in both groups (10 months). The statistically significant differences
      in treatment outcomes in both groups were in favor of myotomy during 2-year
      follow-up. CONCLUSIONS: The data indicates that both methods of treatment might
      be useful in dysphagia control, but better results are obtained after myotomy.
      Repeat interventions are more frequent after endoscopic dilation. One method of
      treatment does not exclude the other. A short period of symptom relief after
      myotomy may suggest the myotomy was incomplete.

PMID- 24296695
TI  - Electron energy loss spectroscopy of polytetrafluoroethylene: experiment and
      first principles calculations.
AB  - We have performed electron energy-loss spectroscopy (EELS) on a 200 kV
      transmission electron microscope (TEM) equipped with a monochromator to
      investigate molecular conformation of polytetrafluoroethylene (PTFE). The
      experimental spectra show several unique features in the low-loss region and the
      onset of carbon K-edge for PTFE. Density function theory (DFT) methods are
      employed to calculate the low-loss and core-loss spectra of PTFE with
      consideration of the effects of phase transitions, chain orientation and
      polarization. The shape and width of the characteristic peaks of the experimental
      spectra are well reproduced in DFT calculations. By comparing the spectra from
      experiments and theory, the detailed information about the conformational
      dependence of EEL spectra for PTFE can be obtained. In the present work, we have
      demonstrated an application of combining high-resolution EELS and DFT
      calculations in both low-loss and core-loss regions to discriminate changes of
      chain conformation and orientation for the polymer with complex phase transition
      behavior. 

PMID- 24296694
TI  - Capsaicin-sensitive cough receptors in lower airway are responsible for cough
      hypersensitivity in patients with upper airway cough syndrome.
AB  - BACKGROUND: Cough hypersensitivity may be related to the pathogenesis of upper
      airway cough syndrome (UACS). The purpose of the study was to investigate the
      role of capsaicin-sensitive cough receptors on the laryngopharynx and lower
      airway in the cough hypersensitivity of patients with UACS. MATERIAL AND METHODS:
      59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39
      healthy volunteers were recruited for the study. Cough threshold C5, defined as
      the lowest concentration of capsaicin required for the induction of >= 5 coughs
      upon exposure to capsaicin, were determined at baseline and after
      laryngopharngeal anesthesia with lidocaine in all the subjects. After induced
      sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and
      calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by
      ELISA. In 15 patients with UACS, sputum cytology and measurement of the above
      mediators were repeated after successful therapy. RESULTS: C5 response to
      capsaicin was significantly lower in the UACS group than in the
      rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) umol/L vs.
      7.8 (3.9, 93.75) umol/L vs. 31.2 (15.6, 62.5) umol/L, H=40.12, P=0.000].
      Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin
      in the subjects of all 3 groups by a similar degree, but the increase in the UACS
      group was still the lowest, with an increased level of histamine, PGE2, and CGRP
      in the induced sputum. When cough resolved with the treatment of cetirizine alone
      or in combination with erythromycin, the levels of CGRP and histamine in the
      induced sputum decreased significantly in 15 patients with UACS, with no obvious
      change in cell differential or concentration of PGE2 in the induced sputum.
      CONCLUSIONS: Laryngeal TRPV1 plays an important role in cough sensitivity, but
      sensitization of capsaicin-sensitive cough receptors in the lower airway may be
      more responsible for the cough hypersensitivity in patients with UACS.

PMID- 24296696
TI  - Inhibition of HBV replication in vivo using helper-dependent adenovirus vectors
      to deliver antiviral RNA interference expression cassettes.
AB  - BACKGROUND: HBV is hyperendemic to southern Africa and parts of Asia, but
      licensed antivirals have little effect on limiting life-threatening complications
      of the infection. Although RNA interference (RNAi)-based gene silencing has shown
      therapeutic potential, difficulties with delivery of anti-HBV RNAi effectors
      remain an obstacle to their clinical use. To address concerns about the transient
      nature of transgene expression and toxicity resulting from immunostimulation by
      recombinant adenovirus vectors (Ads), utility of RNAi-activating anti-HBV helper
      dependent (HD) Ads were assessed in this study. METHODS: Following intravenous
      administration of 5*10(9) unmodified or pegylated HD Ad infectious particles to
      HBV transgenic mice, HBV viral loads and serum HBV surface antigen levels were
      monitored for 12 weeks. Immunostimulation of HD Ads was assessed by measuring
      inflammatory cytokines, hepatic function and immune response to the co-delivered
      LacZ reporter gene. RESULTS: Unmodified and pegylated HD Ads transduced 80-90% of
      hepatocytes and expressed short hairpin RNAs (shRNAs) were processed to generate
      intended HBV-targeting guides. Markers of HBV replication were decreased by
      approximately 95% and silencing was sustained for 8 weeks. Unmodified HD Ads
      induced release of proinflammatory cytokines and there was evidence of an
      adaptive immune response to beta-galactosidase. However the HD Ad-induced innate
      immune response was minimal in preparations that were enriched with infectious
      particles. CONCLUSIONS: HD Ads have potential utility for delivery of therapeutic
      HBV-silencing sequences and alterations of these vectors to attenuate their
      immune responses may further improve their efficacy.

PMID- 24296697
TI  - Identifying the principal modes of variation in human thoracic aorta morphology.
AB  - PURPOSE: Diagnosis and management of thoracic aorta (TA) disease demand the
      assessment of accurate quantitative information of the aortic anatomy. We
      investigated the principal modes of variation in aortic 3-dimensional geometry
      paying particular attention to the curvilinear portion. MATERIALS AND METHODS:
      Images were obtained from extended noncontrast multislice computed tomography
      scans, originally intended for coronary calcium assessment. The ascending, arch,
      and descending aortas of 500 asymptomatic patients (57 +/- 9 y, 81% male) were
      segmented using a semiautomated algorithm that sequentially inscribed circles
      inside the vessel cross-section. Axial planes were used for the descending aorta,
      whereas oblique reconstructions through a toroid path were required for the arch.
      Vessel centerline coordinates and the corresponding diameter values were
      obtained. Twelve size and shape geometric parameters were calculated to perform a
      principal component analysis. RESULTS: Statistics revealed that the geometric
      variability of the TA was successfully explained using 3 factors that account for
      ~80% of total variability. Averaged aortas were reconstructed varying each factor
      in 5 intervals. Analyzing the parameter loadings for each principal component,
      the dominant contributors were interpreted as vessel size (46%), arch unfolding
      (22%), and arch symmetry (12%). Variables such as age, body size, and risk
      factors did not substantially modify the correlation coefficients, although some
      particular differences were observed with sex. CONCLUSIONS: We conclude that
      vessel size, arch unfolding, and symmetry form the basis for characterizing the
      variability of TA morphology. The numerical data provided in this study as
      supplementary material can be exploited to accurately reconstruct the curvilinear
      shape of normal TAs.

PMID- 24296698
TI  - Disseminated pulmonary penicilliosis in a rheumatoid arthritis patient.

PMID- 24296699
TI  - Positron emission tomography/magnetic resonance imaging evaluation of lung
      cancer: current status and future prospects.
AB  - Various designs of positron emission tomography/magnetic resonance imaging
      (PET/MRI) systems have been recently introduced to clinical practice, which have
      overcome preexisting technical challenges concerning the fusion of PET and MRI
      systems. Although further improvements are still necessary especially for bony
      lesions, quantification using current MRI-based attenuation correction techniques
      has been shown to be comparable to that of PET/computed tomography (CT) systems.
      On the basis of the results of previous whole-body MRI studies, PET/MRI is
      expected to show even better performance than PET/CT in M-staging especially for
      brain and liver metastases. Another advantage of PET/MRI over PET/CT, in addition
      to good soft tissue contrast, is the potential reduction in radiation dose. The
      next important hurdle to overcome for its clinical application is the development
      of time-efficient protocols for lung cancer evaluation and interpretation of
      discordant results from both modalities. Multiparametric imaging through PET/MRI
      will help radiologists better understand tumor biology and better evaluate
      treatment response. 

PMID- 24296701
TI  - Prostate cancer: Could sensitive PSA assays expedite salvage radiotherapy?

PMID- 24296702
TI  - Prostate cancer: Visual estimation versus software fusion for MRI-targeted
      biopsy.

PMID- 24296703
TI  - Sperm retrieval techniques.
AB  - Since the advent of intracytoplasmic sperm injection in 1992, sperm retrieval
      procedures have been routinely employed to treat male infertility owing to
      azoospermia. With obstructive azoospermia, sperm is potentially harvestable from
      the vas deferens, epididymis, and testicle using percutaneous and open sperm
      retrieval procedures that are relatively straightforward and reliable. In
      nonobstructive azoospermia, sperm is generally found only in the testicles and
      can often be difficult to retrieve. Several approaches aimed at maximizing sperm
      yield in this condition have been developed, but only 50% of men with
      nonobstructive azoospermia will have clinically usable sperm. Multibiopsy
      testicular sperm extraction (TESE), microdissection TESE, and fine-needle
      aspiration map-guided TESE are three common methods currently employed to locate
      and retrieve sperm in these difficult cases. Other factors that influence the use
      of surgically retrieved sperm for assisted reproduction include differences in
      sperm DNA integrity, the expertise of the surgeon and the andrology laboratory,
      and the described differences in the viability of sperm from different anatomical
      sources after freezing and thawing. 

PMID- 24296705
TI  - Prostate cancer: Dasatinib fails to improve on docetaxel for metastatic CRPC.

PMID- 24296707
TI  - Infection: Utility of midstream urine cultures questioned.

PMID- 24296708
TI  - BPH: Lasers equal TURP in head-to-head study.

PMID- 24296704
TI  - The genetic epidemiology of prostate cancer and its clinical implications.
AB  - Worldwide, familial and epidemiological studies have generated considerable
      evidence of an inherited component to prostate cancer. Indeed, rare highly
      penetrant genetic mutations have been implicated. Genome-wide association studies
      (GWAS) have also identified 76 susceptibility loci associated with prostate
      cancer risk, which occur commonly but are of low penetrance. However, these
      mutations interact multiplicatively, which can result in substantially increased
      risk. Currently, approximately 30% of the familial risk is due to such variants.
      Evaluating the functional aspects of these variants would contribute to our
      understanding of prostate cancer aetiology and would enable population risk
      stratification for screening. Furthermore, understanding the genetic risks of
      prostate cancer might inform predictions of treatment responses and toxicities,
      with the goal of personalized therapy. However, risk modelling and clinical
      translational research are needed before we can translate risk profiles generated
      from these variants into use in the clinical setting for targeted screening and
      treatment. 

PMID- 24296711
TI  - Impact of co-adsorbed oxygen on crotonaldehyde adsorption over gold nanoclusters:
      a computational study.
AB  - Crotonaldehyde (2-butenal) adsorption over gold sub-nanometer particles, and the
      influence of co-adsorbed oxygen, has been systematically investigated by
      computational methods. Using density functional theory, the adsorption energetics
      of crotonaldehyde on bare and oxidised gold clusters (Au13, d = 0.8 nm) were
      determined as a function of oxygen coverage and coordination geometry. At low
      oxygen coverage, sites are available for which crotonaldehyde adsorption is
      enhanced relative to bare Au clusters by 10 kJ mol(-1). At higher oxygen
      coverage, crotonaldehyde is forced to adsorb in close proximity to oxygen
      weakening adsorption by up to 60 kJ mol(-1) relative to bare Au. Bonding
      geometries, density of states plots and Bader analysis, are used to elucidate
      crotonaldehyde bonding to gold nanoparticles in terms of partial electron
      transfer from Au to crotonaldehyde, and note that donation to gold from
      crotonaldehyde also becomes significant following metal oxidation. At high oxygen
      coverage we find that all molecular adsorption sites have a neighbouring,
      destabilising, oxygen adatom so that despite enhanced donation, crotonaldehyde
      adsorption is always weakened by steric interactions. For a larger cluster (Au38,
      d = 1.1 nm) crotonaldehyde adsorption is destabilized in this way even at a low
      oxygen coverage. These findings provide a quantitative framework to underpin the
      experimentally observed influence of oxygen on the selective oxidation of crotyl
      alcohol to crotonaldehyde over gold and gold-palladium alloys. 

PMID- 24296712
TI  - Identification and characterization of GLP-1 receptor-expressing cells using a
      new transgenic mouse model.
AB  - GLP-1 is an intestinal hormone with widespread actions on metabolism. Therapies
      based on GLP-1 are highly effective because they increase glucose-dependent
      insulin secretion in people with type 2 diabetes, but many reports suggest that
      GLP-1 has additional beneficial or, in some cases, potentially dangerous actions
      on other tissues, including the heart, vasculature, exocrine pancreas, liver, and
      central nervous system. Identifying which tissues express the GLP-1 receptor
      (GLP1R) is critical for the development of GLP-1-based therapies. Our objective
      was to use a method independent of GLP1R antibodies to identify and characterize
      the targets of GLP-1 in mice. Using newly generated glp1r-Cre mice crossed with
      fluorescent reporter strains, we show that major sites of glp1r expression
      include pancreatic beta- and delta-cells, vascular smooth muscle, cardiac atrium,
      gastric antrum/pylorus, enteric neurones, and vagal and dorsal root ganglia. In
      the central nervous system, glp1r-fluorescent cells were abundant in the area
      postrema, arcuate nucleus, paraventricular nucleus, and ventromedial
      hypothalamus. Sporadic glp1r-fluorescent cells were found in pancreatic ducts. No
      glp1r-fluorescence was observed in ventricular cardiomyocytes. Enteric and vagal
      neurons positive for glp1r were activated by GLP-1 and may contribute to
      intestinal and central responses to locally released GLP-1, such as regulation of
      intestinal secretomotor activity and appetite. 

PMID- 24296713
TI  - Limited recovery of beta-cell function after gastric bypass despite clinical
      diabetes remission.
AB  - The mechanisms responsible for the remarkable remission of type 2 diabetes after
      Roux-en-Y gastric bypass (RYGBP) are still puzzling. To elucidate the role of the
      gut, we compared beta-cell function assessed during an oral glucose tolerance
      test (OGTT) and an isoglycemic intravenous glucose clamp (iso-IVGC) in: 1) 16
      severely obese patients with type 2 diabetes, up to 3 years post-RYGBP; 2) 11
      severely obese normal glucose-tolerant control subjects; and 3) 7 lean control
      subjects. Diabetes remission was observed after RYGBP. beta-Cell function during
      the OGTT, significantly blunted prior to RYGBP, normalized to levels of both
      control groups after RYGBP. In contrast, during the iso-IVGC, beta-cell function
      improved minimally and remained significantly impaired compared with lean control
      subjects up to 3 years post-RYGBP. Presurgery, beta-cell function, weight loss,
      and glucagon-like peptide 1 response were all predictors of postsurgery beta-cell
      function, although weight loss appeared to be the strongest predictor. These data
      show that beta-cell dysfunction persists after RYGBP, even in patients in
      clinical diabetes remission. This impairment can be rescued by oral glucose
      stimulation, suggesting that RYGBP leads to an important gastrointestinal effect,
      critical for improved beta-cell function after surgery. 

PMID- 24296714
TI  - Glycogen synthase kinase-3beta inhibition augments diabetic endothelial
      progenitor cell abundance and functionality via cathepsin B: a novel therapeutic
      opportunity for arterial repair.
AB  - Progenitor cell therapy is hindered in patients with diabetes mellitus (DM) due
      to cellular senescence. Glycogen synthase kinase-3beta (GSK3beta) activity is
      increased in DM, potentially exacerbating impaired cell-based therapies. Thus, we
      aimed to determine if and how GSK3beta inhibitors (GSKi) can improve therapeutic
      efficacy of endothelial progenitor cells (EPC) from patients with DM. Patients
      with DM had fewer EPCs and increased rates of apoptosis. DM EPCs also exhibited
      higher levels of GSK3beta activity resulting in increased levels of
      phosphorylated beta-catenin. Proteomic profiling of DM EPCs treated with GSKi
      identified 37 nonredundant, differentially regulated proteins. Cathepsin B
      (cathB) was subsequently confirmed to be differentially regulated and showed 40%
      less baseline activity in DM EPCs, an effect reversed by GSKi treatment. Finally,
      in vivo efficacy of cell-based therapy was assessed in a xenotransplant femoral
      wire injury mouse model. Administration of DM EPCs reduced the intima-to-media
      ratio, an effect that was further augmented when DM EPCs were pretreated with
      GSKi yet absent when cathB was antagonized. In DM, increased basal GSK3beta
      activity contributes to accelerated EPC cellular senescence, an effect reversed
      by small molecule antagonism of GSK3beta, which enhanced cell-based therapy after
      vascular injury. 

PMID- 24296715
TI  - Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using
      DPP-4 inhibition and GLP-1 receptor blockade.
AB  - Understanding the incretin pathway has led to significant advancements in the
      treatment of type 2 diabetes (T2D). Still, the exact mechanisms are not fully
      understood. In a randomized, placebo-controlled, four-period, crossover study in
      24 patients with T2D, dipeptidyl peptidase-4 (DPP-4) inhibition and its glucose
      lowering actions were tested after an oral glucose tolerance test (OGTT). The
      contribution of GLP-1 was examined by infusion of the GLP-1 receptor (GLP-1r)
      antagonist exendin-9. DPP-4 inhibition reduced glycemia and enhanced insulin
      levels and the incretin effect (IE). Glucagon was suppressed, and gastric
      emptying (GE) was decelerated. Exendin-9 increased glucose levels and glucagon
      secretion, attenuated insulinemia and the IE, and accelerated GE. With the GLP-1r
      antagonist, the glucose-lowering effects of DPP-4 inhibition were reduced by ~
      50%. However, a significant effect on insulin secretion remained during GLP-1r
      blockade, whereas the inhibitory effects of DPP-4 inhibition on glucagon and GE
      were abolished. Thus, in this cohort of T2D patients with a substantial IE, GLP-1
      contributed ~ 50% to the insulin excursion after an OGTT with and without DPP-4
      inhibition. Thus, a significant DPP-4-sensitive glucose-lowering mechanism
      contributes to glycemic control in T2D patients that may be not mediated by
      circulating GLP-1.

PMID- 24296716
TI  - Hepatic overexpression of ATP synthase beta subunit activates PI3K/Akt pathway to
      ameliorate hyperglycemia of diabetic mice.
AB  - ATP synthase beta subunit (ATPSbeta) had been previously shown to play an
      important role in controlling ATP synthesis in pancreatic beta-cells. This study
      aimed to investigate the role of ATPSbeta in regulation of hepatic ATP content
      and glucose metabolism in diabetic mice. ATPSbeta expression and ATP content were
      both reduced in the livers of type 1 and type 2 diabetic mice. Hepatic
      overexpression of ATPSbeta elevated cellular ATP content and ameliorated
      hyperglycemia of streptozocin-induced diabetic mice and db/db mice. ATPSbeta
      overexpression increased phosphorylated Akt (pAkt) levels and reduced PEPCK and
      G6pase expression levels in the livers. Consistently, ATPSbeta overexpression
      repressed hepatic glucose production in db/db mice. In cultured hepatocytes,
      ATPSbeta overexpression increased intracellular and extracellular ATP content,
      elevated the cytosolic free calcium level, and activated Akt independent of
      insulin. The ATPSbeta-induced increase in cytosolic free calcium and pAkt levels
      was attenuated by inhibition of P2 receptors. Notably, inhibition of calmodulin
      (CaM) completely abolished ATPSbeta-induced Akt activation in liver cells.
      Inhibition of P2 receptors or CaM blocked ATPSbeta-induced nuclear exclusion of
      forkhead box O1 in liver cells. In conclusion, a decrease in hepatic ATPSbeta
      expression in the liver, leading to the attenuation of ATP-P2 receptor-CaM-Akt
      pathway, may play an important role in the progression of diabetes. 

PMID- 24296718
TI  - Long-term IKK2/NF-kappaB signaling in pancreatic beta-cells induces immune
      mediated diabetes.
AB  - Type 1 diabetes is a multifactorial inflammatory disease in genetically
      susceptible individuals characterized by progressive autoimmune destruction of
      pancreatic beta-cells initiated by yet unknown factors. Although animal models of
      type 1 diabetes have substantially increased our understanding of disease
      pathogenesis, heterogeneity seen in human patients cannot be reflected by a
      single model and calls for additional models covering different aspects of human
      pathophysiology. Inhibitor of kappaB kinase (IKK)/nuclear factor-kappaB (NF
      kappaB) signaling is a master regulator of inflammation; however, its role in
      diabetes pathogenesis is controversially discussed by studies using different
      inhibition approaches. To investigate the potential diabetogenic effects of NF
      kappaB in beta-cells, we generated a gain-of-function model allowing conditional
      IKK2/NF-kappaB activation in beta-cells. A transgenic mouse model that expresses
      a constitutively active mutant of human IKK2 dependent on Pdx-1 promoter activity
      (IKK2-CA(Pdx-1)) spontaneously develops full-blown immune-mediated diabetes with
      insulitis, hyperglycemia, and hypoinsulinemia. Disease development involves a
      gene expression program mimicking virus-induced diabetes and allergic
      inflammatory responses as well as increased major histocompatibility complex
      class I/II expression by beta-cells that could collectively promote diabetes
      development. Potential novel diabetes candidate genes were also identified.
      Interestingly, animals successfully recovered from diabetes upon transgene
      inactivation. Our data give the first direct evidence that beta-cell-specific
      IKK2/NF-kappaB activation is a potential trigger of immune-mediated diabetes.
      Moreover, IKK2-CA(Pdx-1) mice provide a novel tool for studying critical
      checkpoints in diabetes pathogenesis and mechanisms governing beta-cell
      degeneration/regeneration. 

PMID- 24296719
TI  - The role of zinc dynamics in growth hormone secretion.
AB  - Human growth hormone (GH) causes a variety of physiological and metabolic effects
      in humans and plays a pivotal role in postnatal growth. In somatotroph cells of
      the anterior pituitary, GH is stored in concentrated forms in secretory granules
      to be rapidly released upon GH-releasing hormone stimulation. During the process
      of secretory granule biogenesis, self-association of GH occurs in the
      compartments of the early secretory pathway (endoplasmic reticulum and Golgi
      complex). Since this process is greatly facilitated by the presence of zinc ions,
      it is of importance to understand the potential role of zinc transporters that
      participate in the fine-tuning of zinc homeostasis and dynamics, particularly in
      the early secretory pathway. Thus, the role of zinc transporters in supplying the
      secretory pathway with the sufficient amount of zinc required for the biogenesis
      of GH-containing secretory granules is essential for normal secretion. This
      report, illustrated by a clinical case report on transient neonatal zinc
      deficiency, focuses on the role of zinc in GH storage in the secretory granules
      and highlights the role of specific zinc transporters in the early secretory
      pathway. (c) 2013 S. Karger AG, Basel. 

PMID- 24296717
TI  - Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits
      reveals mechanistic heterogeneity.
AB  - Patients with established type 2 diabetes display both beta-cell dysfunction and
      insulin resistance. To define fundamental processes leading to the diabetic
      state, we examined the relationship between type 2 diabetes risk variants at 37
      established susceptibility loci, and indices of proinsulin processing, insulin
      secretion, and insulin sensitivity. We included data from up to 58,614
      nondiabetic subjects with basal measures and 17,327 with dynamic measures. We
      used additive genetic models with adjustment for sex, age, and BMI, followed by
      fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci
      into five major categories based on their relationship to these continuous
      glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was
      characterized by primary effects on insulin sensitivity. The second cluster
      (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and
      fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects
      in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1,
      CDKN2A/2B) was defined by loci influencing insulin processing and secretion
      without a detectable change in fasting glucose levels. The final group contained
      20 risk loci with no clear-cut associations to continuous glycemic traits. By
      assembling extensive data on continuous glycemic traits, we have exposed the
      diverse mechanisms whereby type 2 diabetes risk variants impact disease
      predisposition.

PMID- 24296721
TI  - Posttraumatic stress disorder and medication nonadherence in patients with
      uncontrolled hypertension.

PMID- 24296720
TI  - T-cell aging in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: With progressive age, the immune system and the propensity for
      abnormal immunity change fundamentally. Individuals greater than 50 years of age
      are not only more susceptible to infection and cancer, but also at higher risk
      for chronic inflammation and immune-mediated tissue damage. The process of
      immunosenescence is accelerated in rheumatoid arthritis (RA). RECENT FINDINGS:
      Premature T-cell senescence occurs not only in RA, but also has been involved in
      morbidity and mortality of chronic HIV infection. Senescent cells acquire the
      'senescence-associated secretory phenotype', which promotes and sustains tissue
      inflammation. Molecular mechanisms underlying T-cell aging are beginning to be
      understood. In addition to the contraction of T-cell diversity because of uneven
      clonal expansion, senescent T cells have defects in balancing cytoplasmic kinase
      and phosphatase activities, changing their activation thresholds. Also, leakiness
      in repairing DNA lesions and uncapped telomeres imposes genomic stress. Age
      induced changes in the tissue microenvironment may alter the T-cell responses.
      SUMMARY: Gain-of-function and loss-of-function in senescent T cells undermine
      protective immunity and create the conditions for chronic tissue inflammation, a
      combination typically encountered in RA. Genetic programs involved in T-cell
      signaling and DNA repair are of high interest in the search for underlying
      molecular defects.

PMID- 24296723
TI  - Stabilizing vitamin D(3) by conformationally selective co-crystallization.
AB  - A four-membered square-shaped H-bonding structure was successfully designed to
      synthesize vitamin D3 co-crystals. The co-crystallization process was found to be
      conformationally selective to result in topochemically stable materials. 

PMID- 24296722
TI  - Innate type 2 response to Alternaria extract enhances ryegrass-induced lung
      inflammation.
AB  - BACKGROUND: Exposure to the fungal allergen Alternaria alternata as well as
      ryegrass pollen has been implicated in severe asthma symptoms during
      thunderstorms. We have previously shown that Alternaria extract induces innate
      type 2 lung inflammation in mice. We hypothesized that the innate eosinophilic
      response to Alternaria extract may enhance lung inflammation induced by ryegrass.
      METHODS: Mice were sensitized to ryegrass allergen and administered a single
      challenge with A. alternata extract before or after final ryegrass challenges.
      Levels of eosinophils, neutrophils, Th2 cells, innate lymphoid cells (ILC2),
      interleukin (IL)-5 and IL-13 in bronchoalveolar lavage (BAL) as well as
      inflammation and mucus were assessed. RESULTS: Mice receiving ryegrass
      sensitization and challenge developed an eosinophilic lung response. A single
      challenge with Alternaria extract given 3 days before or 3 days after ryegrass
      challenges resulted in increased eosinophils, peribronchial inflammation and
      mucus production in the airways compared with ryegrass-only challenges. Type 2
      ILC2 and Th2 cell recruitment to the airways was increased after Alternaria
      extract exposure in ryegrass-challenged mice. Innate immune challenges with
      Alternaria extract induced BAL eosinophilia, Th2 cell recruitment as well as ILC2
      expansion and proliferation. CONCLUSIONS: A single exposure to Alternaria extract
      in ryegrass-sensitized and -challenged mice enhances the type 2 lung inflammatory
      response, including airway eosinophilia, peribronchial infiltrate, and mucus
      production, possibly through Th2 cell recruitment and ILC2 expansion. If
      translated to humans, exposure to both grass pollen and Alternaria may be a
      potential cause of thunderstorm-related asthma.

PMID- 24296724
TI  - Attitudes of health care professionals towards female obese patients.
AB  - OBJECTIVE: The health care setting has been reported to be one main source of
      weight stigma repeatedly; however, studies comparing different professions have
      been lacking. METHODS: 682 health care professionals (HCP) of a large German
      university hospital were asked to fill out a questionnaire on stigmatizing
      attitudes, perceived causes of obesity, and work-related impact of obesity.
      Stigmatizing attitudes were assessed on the Fat Phobia Scale (FPS) based on a
      vignette describing a female obese patient. RESULTS: Only 25% graded current
      health care of obese patients to be 'good' or 'very good'. 63% of all HCPs
      'somewhat' or 'strongly' agreed that it was often difficult to get the resources
      needed in order to care for obese patients. The mean FPS score was comparable to
      that in the general public (M = 3.59), while nursing staff showed slightly more
      positive attitudes compared to physicians and therapists. Higher age, higher BMI,
      and ascribing personal responsibility for obesity to the individual were
      associated with a higher level of stigmatizing attitudes. The nursing staff
      agreed on obesity as an illness to a greater extent while physicians attributed
      obesity to the individual. CONCLUSIONS: In summary, by making complex models on
      the causes of obesity known among health care professionals, stigmatizing
      attitudes might be reduced. Ongoing further education for health care
      professionals ought to be part of anti-stigma campaigns in the medical field.

PMID- 24296725
TI  - Microbiome composition by pyrosequencing in mesenteric lymph nodes of rats with
      CCl4-induced cirrhosis.
AB  - BACKGROUND: The cross talk between the gut microbiota and the immune system,
      which is essential to maintain homeostasis, takes place at the intestinal
      lymphoid tissue such as the mesenteric lymph nodes (MLNs). Here, we investigated
      the presence of bacterial DNA in MLNs of control and cirrhotic rats and its
      relationship with inflammatory responses. METHODS: The MLN microbiome of
      cirrhotic rats with ascites, which was induced by carbon tetrachloride (CCl4),
      was compared to that of control rats using quantitative real-time PCR and
      pyrosequencing of the 16S rRNA gene. Cytokines in blood samples were assessed by
      ELISA. RESULTS: Unexpectedly, sequence analysis revealed a high microbial
      diversity in the MLNs of both control and cirrhotic rats with Proteobacteria as
      one of the most dominant phylum. CCl4-induced liver injury was not associated
      with a change in bacterial load, but it was linked to a decrease in microbial
      diversity (p < 0.05) and alterations in the microbial community in MLNs. A high
      proportion of Bifidobacterium animalis was also positively correlated with
      elevated interleukin-10 expression (p = 0.002, false discovery rate = 0.03, r =
      0.94). CONCLUSIONS: For the first time, the high microbial diversity observed in
      MLNs of both controls and CCl4-induced cirrhotic rats provides evidence that
      bacterial translocation is more than a mere dichotomic phenomenon.

PMID- 24296727
TI  - Non-symmetric diphosphines based on the imidazole scaffold: an unusual group
      interchange involving Pd-CH3 and (imidazole)P-Ph cleavage.
AB  - Two regioisomeric, non-symmetric P(C2)P(N)-imidazoles, t-Bu2PNCH=CHNC(PPh2) (L1,
      P(C2) = PPh2, P(N) = P(t-Bu)2) and Ph2PNCH=CHNC[P(t-Bu)2] (L2, P(C2) = P(t-Bu)2,
      P(N) = PPh2), respectively, show dramatic differences in the reactivity of the N
      bound phosphine group; the L2 isomer is extremely sensitive to P-N bond cleavage
      by nucleophiles, and when coordinated to the PdCl(Me) fragment it undergoes
      facile interchange of one P(N) phenyl with the methyl originating from Pd.

PMID- 24296726
TI  - Strategies for a direct characterization of phosphoproteins on hydroxyapatite
      surfaces.
AB  - We show in this work how systems formed by phosphoproteins on calcium phosphate
      surfaces can be directly characterized, in real time, in liquid medium, without
      the need for elution or labeling. Specifically, we show how this is possible by
      applying three different techniques: ellipsometry, quartz crystal microbalance
      with dissipation, and atomic force microscopy-based friction force spectroscopy.
      We apply these techniques to study two different model systems, i.e. those formed
      upon the adsorption of two model phosphoproteins (kappa- and beta-casein) on
      hydroxyapatite (HA) surfaces. Information on the kinetics of adsorption, surface
      excess, viscoelasticity, water content, thickness of the layers, and protein
      surface interaction is provided. Results indicate that both phosphoproteins form
      homogeneous elastic highly hydrated monolayers on the HA surfaces, the strength
      of beta-casein layers being higher by approximately a factor of 4. Based on the
      experimental results, models for the conformation of kappa- and beta-casein
      molecules adsorbed on HA surfaces are proposed.

PMID- 24296728
TI  - A DFT study of oxygen dissociation on platinum based nanoparticles.
AB  - Density functional theory calculations are performed on 38 and 79 metal atom
      truncated octahedron clusters to study oxygen dissociation as a model for the
      initial stage of the oxygen reduction reaction. Pure platinum and alloyed
      platinum-titanium core-shell systems are investigated. It is found that
      barrierless oxygen dissociation occurs on the (111) facet of the pure platinum
      clusters. A barrier of ~0.3 eV is observed on the (100) facet. For the alloyed
      cluster, dissociation barriers are found on both facets, typically ~0.6 eV. The
      differences between the two systems are attributed to the ability of oxygen to
      distort the (111) surface of the pure platinum clusters. We show that flexibility
      of the platinum shell is crucial in promotion of fast oxygen dissociation.
      However, the titanium core stabilises the platinum shell upon alloying, resulting
      in a less easily distortable surface. Therefore, whilst an alloyed platinum
      titanium electrocatalyst has certain advantages over the pure platinum
      electrocatalyst, we suggest alloying with a more weakly interacting metal will be
      beneficial for facilitating oxygen dissociation.

PMID- 24296729
TI  - Amiodarone and concurrent antiretroviral therapy: a case report and review of the
      literature.
AB  - Therapy for HIV often can make pharmacologic management of comorbidities
      challenging since many antiretroviral agents significantly modulate drug
      metabolism pathways. Amiodarone is commonly used to control cardiac arrhythmias;
      however, it is recognized as having a narrow therapeutic window with potential
      for significant drug toxicity. Amiodarone is metabolized by CYP3A4, CYP2C8 and
      CYP1A1 to an active metabolite and therefore may be affected by comedications
      that modulate these isoenzymes. Since amiodarone is frequently associated with
      toxicity, the Heart Rhythm Society (formerly the North American Society of Pacing
      and Electrophysiology) developed guidelines to minimize the potential for adverse
      events. However, recommendations for the management of situations where
      amiodarone must be given with a drug that significantly affects its metabolism
      are lacking. This paper will discuss our experience with a case of concurrent
      amiodarone and antiretroviral therapy, as well as provide a review of
      interactions that may lead to toxicity or potential treatment failure with
      amiodarone. Primary literature was identified through Medline (1946 to May 2013)
      and Embase (1980 to May 2013), using the following terms: amiodarone,
      antiretroviral, HIV, cytochrome P450 and drug interaction. Case reports, studies
      of xenobiotic interactions with amiodarone in healthy volunteers, and in vitro
      studies that investigated metabolic pathways of amiodarone were reviewed.
      Although clinical data was limited, several cases support the finding that potent
      inhibitors or inducers of cytochrome P450 may lead to amiodarone toxicity or lack
      of therapeutic effect, respectively. As well, several case reports, in vitro data
      and clinical investigations have associated some of the antiretrovirals with QT
      prolongation, which may result in additive cardiotoxicity in patients also
      receiving amiodarone. Therefore, to manage situations where amiodarone must be
      used with concurrent interacting antiretrovirals, we recommend a monitoring plan
      that follows the Heart Rhythm Society guidelines, however with the addition of
      serial therapeutic drug level monitoring and frequent electrocardiography to
      minimize potential toxicity and successfully manage both conditions. 

PMID- 24296730
TI  - Family centered care at the end of a child's life: we must get this right.

PMID- 24296731
TI  - Non-heart beating donors (NHBD): is a "paradigm shift" feasible in Italy?

PMID- 24296732
TI  - Neurological picture. Cortical susceptibility-weighted imaging hypointensity
      after stroke-like episode in MELAS.

PMID- 24296734
TI  - How do environmental factors influence walking in groups? A walk-along study.
AB  - Insufficient attention has been given to the influence of context on health
      related behaviour change. This article reports on walk-along interviews conducted
      with 10 leaders of walking groups while leading their groups to investigate the
      influence of contextual factors on walking behaviours in groups. Data analysis
      used ideas from thematic analysis and grounded theory, approaching the data
      inductively. We identified that characteristics of place influenced the type of
      walking that people do in groups and the processes used by walkers to make sense
      of their behaviours in the places they walk. This research provides insight into
      how place influences walking in groups. It also suggests recommendations for co
      ordinators and policymakers that could be used to facilitate behaviour change,
      when designing interventions targeting public health within the community. 

PMID- 24296733
TI  - Artemisinin triggers a G1 cell cycle arrest of human Ishikawa endometrial cancer
      cells and inhibits cyclin-dependent kinase-4 promoter activity and expression by
      disrupting nuclear factor-kappaB transcriptional signaling.
AB  - Relatively little is known about the antiproliferative effects of artemisinin, a
      naturally occurring antimalarial compound from Artemisia annua, or sweet
      wormwood, in human endometrial cancer cells. Artemisinin induced a G1 cell cycle
      arrest in cultured human Ishikawa endometrial cancer cells and downregulated
      cyclin-dependent kinase-2 (CDK2) and CDK4 transcript and protein levels. Analysis
      of CDK4 promoter-luciferase reporter constructs showed that the artemisinin
      ablation of CDK4 gene expression was accounted for by the loss of CDK4 promoter
      activity. Chromatin immunoprecipitation demonstrated that artemisinin inhibited
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      subunit p65 and p50 interactions with the endogenous Ishikawa cell CDK4 promoter.
      Coimmunoprecipitation revealed that artemisinin disrupts endogenous p65 and p50
      nuclear translocation through increased protein-protein interactions with IkappaB
      alpha, an NF-kappaB inhibitor, and disrupts its interaction with the CDK4
      promoter, leading to a loss of CDK4 gene expression. Artemisinin treatment
      stimulated the cellular levels of IkappaB-alpha protein without altering the
      level of IkappaB-alpha transcripts. Finally, expression of exogenous p65 resulted
      in the accumulation of this NF-kappaB subunit in the nucleus of artemisinin
      treated and artemisinin-untreated cells, reversed the artemisinin downregulation
      of CDK4 protein expression and promoter activity, and prevented the artemisinin
      induced G1 cell cycle arrest. Taken together, our results demonstrate that a key
      event in the artemisinin antiproliferative effects in endometrial cancer cells is
      the transcriptional downregulation of CDK4 expression by disruption of NF-kappaB
      interactions with the CDK4 promoter. 

PMID- 24296735
TI  - Use and effectiveness of lapse prevention strategies among pregnant smokers.
AB  - Little is known about the use of lapse prevention strategies to help smokers
      manage situation-triggered urges to smoke. Pregnant smokers (N = 174)
      participating in an intervention trial reported use of cognitive-behavioural
      lapse prevention strategies and smoking abstinence (biochemically verified).
      Participants typically enacted few strategies. Distraction strategies were most
      commonly used. Total number of strategies used did not predict abstinence.
      However, using 'self-talk' (odds ratio (OR) = 3.44, 95% confidence interval =
      1.14-10.40) or 'avoiding spending time with other smokers' (OR = 4.01, 95%
      confidence interval = 1.34-11.95) independently increased the odds of abstinence.
      The promotion of these and other under-utilised evidence-based strategies
      warrants further attention. 

PMID- 24296736
TI  - Using established predictors of post-traumatic stress to explain variations in
      recovery outcomes among orthopedic patients.
AB  - The present studies examine whether information contained in medical records can
      be used to predict outcomes following two orthopedic procedures: repair of hip
      fracture and total knee replacement. Study 1 reports the acute, in-hospital
      recovery data from the medical records of 119 hip fracture patients. Study 2 is a
      prospective, longitudinal investigation of 3-month postoperative recovery of 110
      total knee replacement patients. Patients characterized by a greater number of
      post-traumatic stress risk factors experienced poorer outcomes following
      orthopedic surgery. Our results suggest that patients at risk for negative
      outcomes can be identified by information readily available to medical personnel.

PMID- 24296737
TI  - Predicting safe sex: Assessment of autoregressive and cross-lagged effects within
      the Theory of Planned Behavior.
AB  - Despite its popularity, few studies have assessed the temporal stability and
      cross-lagged effects of the Theory of Planned Behavior factors: Attitude,
      subjective norms and self-efficacy. For this study, 298 adolescent learners from
      KwaZulu-Natal, South Africa, filled out a Theory of Planned Behavior
      questionnaire on teenage pregnancy at baseline and after 6 months. Structural
      equation modeling showed that there were considerable cross-lagged effects
      between attitude and subjective norms. Temporal stability was moderate with test
      retest correlations ranging from 0.37 to 0.51 and the model was able to predict
      intentions to have safe sex (R2 = 0.69) Implications for practice and future
      research are discussed.

PMID- 24296738
TI  - Investigating the impact of gender and existential anxiety on the willingness to
      participate in point-of-care testing for cardiovascular disease.
AB  - Two studies (N = 136) investigated whether or not gender or mortality reminders
      would impact middle-aged and older adults' appraisal of a novel point-of-care
      testing device for cardiovascular disease risk. Middle-aged females were
      significantly more likely to positively appraise and commit to using the device
      compared to middle-aged males, but there were no such gender differences among
      older adults. Both studies also failed to support hypotheses that existential
      concerns would lead to avoidance of the device. When taken together, the findings
      suggest that similar devices may beneficially affect screening behaviours and
      underscore a need to target middle-aged males for cardiovascular screening
      interventions. 

PMID- 24296739
TI  - Coping mediates the relationship between disease severity and illness
      intrusiveness among chronically ill patients.
AB  - Reducing perceptions of illness intrusiveness may improve quality of life and
      mental health among patients with cardiopulmonary disease. To better understand
      relationships between coping style, locus of control, perceived illness
      intrusiveness, and disease severity, we analyzed data from 227 older Veterans
      with chronic obstructive pulmonary disease or congestive heart failure.
      Regressions revealed illness intrusiveness to be associated with younger age and
      greater disease severity, less internal locus of control, and avoidant/emotion
      focused coping. Avoidant/emotion-focused coping but not active coping mediated
      the relationship between illness severity and illness intrusiveness. Findings
      suggest that supportive psychological interventions may reduce illness
      intrusiveness by targeting an avoidant/emotion-focused coping style and
      associated behaviors.

PMID- 24296740
TI  - Living together with age-related macular degeneration: An interpretative
      phenomenological analysis of sense-making within a dyadic relationship.
AB  - In this article, we present an idiographic analysis of a couple's experience of
      living and coming to terms with age-related macular degeneration. Interpretative
      phenomenological analysis was used to explore three joint interviews, conducted
      over an 18-month period, with a married couple (aged 82 and 77 years) both living
      with age-related macular degeneration. Three themes are discussed: the disruption
      of vision impairment, managing mutual deterioration and resilience through
      togetherness. We discuss the existential challenges of vision impairment and
      consider the applicability of Galvin and Todres' typology of well-being as a
      means of understanding well-being in older adults. 

PMID- 24296741
TI  - Using Rasch analysis to evaluate the validity of the diabetes-specific version of
      the Illness Perception Questionnaire--Revised.
AB  - This study used Rasch analysis to examine the psychometric validity of the
      Illness Perception Questionnaire--Revised to assess beliefs about diabetes in 470
      participants with Type 2 diabetes and 71 participants with Type 1 diabetes. All
      Illness Perception Questionnaire--Revised scales had psychometric issues, which
      included poorly utilised response categories, poor scale precision and
      multidimensionality. Following re-engineering, only four of the eight scales
      (Consequences, Illness coherence, Timeline cyclical and Emotional
      representations) were psychometrically adequate according to the Rasch model. The
      diabetes-specific version of the Illness Perception Questionnaire--Revised
      provides suboptimal assessment of beliefs held by patients with diabetes.

PMID- 24296742
TI  - Identity transformation and a changed lifestyle following dramatic weight loss
      and body-contouring surgery: An exploratory study.
AB  - This article reports on two major quality-of-life perception changes for patients
      who had undergone plastic surgery following dramatic weight loss. The
      exploratory, qualitative study was undertaken with 20 patients from one teaching
      hospital. In-depth interviews were conducted, and a thematic analysis of the data
      was undertaken. The results provide unique glimpses of surgical consumption
      empowering and facilitating 'identity transformation', embracing improved
      physical function and enhanced self-esteem, confidence and quality of life, and a
      'changed lifestyle'. For a minority, identity transformation was sometimes
      interrupted by 'identity lag', posing the need for additional health-care support
      throughout the adjustment process. The study provides additional insight into
      existing quantitative studies, adding to the body of knowledge in this area. 

PMID- 24296743
TI  - Molecular characterization of repetitive DNA sequences from B chromosome in
      Plantago lagopus L.
AB  - In Plantagolagopus the B chromosome has been reported by our laboratory to be the
      result of massive amplification of ribosomal DNA sequences. However, the presence
      of transposable elements and other repetitive DNA sequences together with rDNA
      could not be ruled out. The present study clearly demonstrated the presence of
      transposable elements in the B chromosomes. These transposable elements were
      characterized and their nature assessed. Physical mapping using double
      fluorescent in situ hybridization was performed using DNA probes for 5S and copia
      elements. The results clearly proved that the B chromosome is a mix of 5S, 45S
      rDNA and transposable elements. Based on the FISH and Fiber-FISH patterns, it can
      be concluded that while 45S rDNA sequences are restricted to the subtelomeric
      regions, the 5S rDNA sequences are interspersed with transposons in the body of
      the B chromosome. These results have further enhanced our understanding of the
      organization and evolution of B chromosomes.

PMID- 24296744
TI  - Dissemination and implementation of the ARIA guidelines for allergic rhinitis in
      general practice.
AB  - BACKGROUND: Allergic rhinitis (AR) is a prevalent problem in general practice.
      The first evidence-based guidelines for AR, the ARIA guidelines, were published
      and have been updated repeatedly since 2001 in order to improve the care of AR
      patients. Very limited information, however, is available on the impact of these
      guidelines on everyday clinical practice. The aim of this study was to evaluate
      the dissemination and implementation of the ARIA guidelines in general practice.
      METHODS: Three hundred and fifty Flemish general practitioners (GPs) were
      recruited to complete a questionnaire covering their demographic and professional
      characteristics, awareness, perception and implementation of the ARIA guidelines.
      To assess compliance with the ARIA treatment recommendations, 4 fictitious case
      scenarios of AR were presented, in which the respondents were asked to select the
      treatment of choice. RESULTS: Of the 350 GPs included, only 31% were aware of the
      ARIA guidelines and 10% stated that they implement them. For the diagnosis of AR,
      71% of the GPs ask specific IgE tests or perform skin prick tests, whereas only
      29% perform an anterior rhinoscopy. ARIA users are more likely to screen for
      concomitant asthma. In the clinical-case section, there was a large variability
      in proposed therapeutic strategies. Adherence to the evidence-based ARIA
      treatment guidelines was low, but recent graduation was a significant predictor
      of compliance with these recommendations. CONCLUSIONS: The ARIA guidelines remain
      relatively unknown among Flemish GPs and even those who are aware of them still
      tend to treat AR independently of the guideline recommendations.

PMID- 24296745
TI  - Bubble bursting as an aerosol generation mechanism during an oil spill in the
      deep-sea environment: laboratory experimental demonstration of the transport
      pathway.
AB  - Oil spills in the deep-sea environment such as the 2010 Deep Water Horizon oil
      spill in the Gulf of Mexico release vast quantities of crude oil into the sea
      surface environment. Various investigators have discussed the marine transport
      and fate of the oil into different environmental compartments (air, water,
      sediment, and biota). The transport of the oil into the atmosphere in these
      previous investigations has been limited to only evaporation, a volatility
      dependent pathway. In this work, we studied the aerosolization of oil spill
      matter via bursting bubbles as they occur during whitecaps in a laboratory
      aerosolization reactor. By evaluating the alkane content in oil mousse, crude
      oil, the gas phase, and particulate matter we clearly demonstrate that
      aerosolization via bursting bubbles is a solubility and volatility independent
      transport pathway for alkanes. The signature of alkane fractions in the native
      oil and aerosolized matter matched well especially for the less volatile alkanes
      (C20-C29). Scanning electron microscope interfaced with energy dispersive X-ray
      images identified the carbon fractions associated with salt particles of
      aerosols. Theoretical molecular dynamics simulations in the accompanying paper
      lend support to the observed propensity for alkanes at air-salt water interfaces
      of breaking bubbles and the produced droplets. The presence of a dispersant in
      the aqueous phase increased the oil ejection rate at the surface especially for
      the C20-C29 alkanes. The information presented here emphasizes the need to
      further study sea-spray aerosols as a possible transport vector for spilled oil
      in the sea surface environment. 

PMID- 24296746
TI  - Oral administration of Lactobacillus reuteri during the first year of life
      reduces caries prevalence in the primary dentition at 9 years of age.
AB  - The aim of this study was to evaluate the effect on oral health, at age 9 years,
      of daily oral supplementation with the probiotic Lactobacillus reuteri, strain
      ATCC 55730, to mothers during the last month of gestation and to children through
      the first year of life. The study was a single-blind, placebo-controlled,
      multicenter trial involving 113 children: 60 in the probiotic and 53 in the
      placebo group. The subjects underwent clinical and radiographic examination of
      the primary dentition and carious lesions, plaque and gingivitis were recorded.
      Saliva and plaque were sampled for determination of mutans streptococci (MS) and
      lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA).
      Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo
      group were caries-free (p < 0.01). The prevalence of approximal caries lesions
      was lower in the probiotic group (0.67 +/- 1.61 vs. 1.53 +/- 2.64; p < 0.05) and
      there were fewer sites with gingivitis compared to the placebo group (p < 0.05).
      There were no significant differences between the groups with respect to
      frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride
      supplements (p < 0.05). There were no intergroup differences with respect to L.
      reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems
      that daily supplementation with L. reuteri from birth and during the first year
      of life is associated with reduced caries prevalence and gingivitis score in the
      primary dentition at 9 years of age.

PMID- 24296747
TI  - Transfer rates from nonprocedure hospitals after initial admission and outcomes
      among elderly patients with acute myocardial infarction.
AB  - IMPORTANCE: It is unknown whether hospital transfer rates for patients with acute
      myocardial infarction admitted to nonprocedure hospitals (facilities that do not
      provide catheterization) vary and whether these rates further influence
      revascularization rates, length of stay, and mortality. OBJECTIVES: To examine
      hospital differences in transfer rates for elderly patients with acute myocardial
      infarction across nonprocedure hospitals and to determine whether these rates are
      associated with revascularization rates, length of stay, and mortality. DESIGN,
      SETTING, AND PARTICIPANTS: We used Medicare claims data from January 1, 2006, to
      December 31, 2008, to assess transfer rates in nonprocedure hospitals, stratified
      according to transfer rates as low (<= 20%), mid-low (>20%-30%), mid-high (>30%
      40%), or high (>40%). Data were analyzed for 55,962 Medicare fee-for-service
      patients admitted to 901 nonprocedure US hospitals with more than 25 admissions
      per year for acute myocardial infarction. MAIN OUTCOMES AND MEASURES: We compared
      rates of catheterization, percutaneous coronary intervention, and coronary artery
      bypass graft surgery during hospitalization and within 60 days, as well as
      hospital total length of stay, across groups. We measured risk-standardized
      mortality rates at 30 days and 1 year. RESULTS The median transfer rate was 29.4%
      (interquartile range [25th-75th percentile], 21.8%-37.8%). Higher transfer rates
      were associated with higher rates of catheterization (P < .001), percutaneous
      coronary intervention (P < .001), and coronary artery bypass graft surgery (P <
      .001). Median length of stay was not meaningfully different across the groups.
      There was no meaningful evidence of associations between transfer rates and risk
      standardized mortality at 30 days (mean [SD], 22.3% [2.6%], 22.1% [2.3%], 22.3%
      [2.4%], and 21.7% [2.1%], respectively; P = .054) or 1 year (43.9% [2.3%], 43.6%
      [2.2%], 43.5% [2.4%], and 42.8% [2.2%], respectively; P < .001) for low, mid-low,
      mid-high, and high transfer groups. CONCLUSIONS AND RELEVANCE: Nonprocedure
      hospitals vary substantially in their use of the transfer process for elderly
      patients admitted with acute myocardial infarction. High-transfer hospitals had
      greater use of invasive cardiac procedures after admission compared with low
      transfer hospitals. However, higher transfer rates were not associated with a
      significantly lower risk-standardized mortality rate at 30 days. Moreover, at 1
      year there was only a 1.1% difference (42.8% vs 43.9%) between hospitals with
      higher and lower transfer rates. These findings suggest that, as a single
      intervention, promoting the transfer of patients admitted with acute myocardial
      infarction may not improve hospital outcomes.

PMID- 24296748
TI  - Interaction between intradialytic exercise and hemodialysis adequacy.
AB  - BACKGROUND/AIMS: According to mathematical modeling, intradialytic exercise of
      sufficient intensity and duration implemented in the second half of dialysis
      should be as efficacious as increasing dialysis time for dialysis adequacy. This
      assumption has not been tested in vivo. METHODS: In this controlled trial, 11
      hemodialysis (HD) patients (mean (SD) age 56 (13) years) were recruited. Each
      patient completed three trial arms in a randomized order: routine care (CONT),
      increased HD time of 30 min (TIME), and intradialytic exercise (EXER), 60 min of
      cycling at 90% of the lactate threshold in the last 90 min of HD. The primary
      outcome was eKt/Vurea. Secondary outcomes included reduction and rebound ratios
      of urea, creatinine, phosphate and beta2-microglobulin. Outcomes were calculated
      from blood sampling collected pre-, post- and 30 min post-HD and confirmed with
      dialysate sampling. RESULTS: Exercise was not as efficacious as increased HD time
      for eKt/Vurea (EXER vs. CONT, mean change (95% CI): 0.03 (-0.05 to 0.12); TIME
      vs. CONT: 0.15 (0.05-0.26)). Exercise was less efficacious at improving reduction
      ratios of urea and creatinine. However, exercise was more efficacious than
      increased dialysis time for phosphate reduction ratio (EXER vs. CONT: 8.6% (0.5
      16.7); TIME vs. CONT: 5.0% (-1.0 to 11.1)). CONCLUSION: This study utilized a
      rigorously controlled in vivo design to test mathematical models and assumptions
      regarding dialysis adequacy. Intradialytic exercise towards the end of HD cannot
      replace the prescription of increased HD time for dialysis adequacy, but may be
      an adjunctive therapy for serum phosphate control.

PMID- 24296749
TI  - A monoclonal antibody interferes with TIMP-2 binding and incapacitates the MMP-2
      activating function of multifunctional, pro-tumorigenic MMP-14/MT1-MMP.
AB  - Matrix metalloproteinases (MMPs) and, especially membrane type 1 (MT1)-MMP/MMP
      14, are promising drug targets in malignancies. In contrast with multiple small
      molecule and protein pan-inhibitors of MT1-MMP cleavage activity, the murine 9E8
      monoclonal antibody targets the MMP-2-activating function of cellular MT1-MMP
      alone, rather than the general proteolytic activity and the pro-migratory
      function of MT1-MMP. Furthermore, the antibody does not interact in any
      detectable manner with other members of the membrane type (MT)-MMP family. The
      mechanism of this selectivity remained unknown. Using mutagenesis, binding and
      activity assays, and modeling in silico, we have demonstrated that the 9E8
      antibody recognizes the MT-loop structure, an eight residue insertion that is
      specific for MT-MMPs and that is distant from the MT1-MMP active site. The
      binding of the 9E8 antibody to the MT-loop, however, prevents tissue inhibitor of
      metalloproteinases-2 (TIMP-2) association with MT1-MMP. As a result, the 9E8
      antibody incapacitates the TIMP-2-dependent MMP-2-activating function alone
      rather than the general enzymatic activity of human MT1-MMP. The specific
      function of the 9E8 antibody we determined directly supports an essential, albeit
      paradoxical, role of the protein inhibitor (TIMP-2) in MMP-2 activation via a
      unique membrane-tethered mechanism. In this mechanism, the formation of a tri
      molecular MT1-MMPTIMP-2MMP-2 complex is required for both the capture of the
      soluble MMP-2 proenzyme by cells and then its well-controlled conversion into the
      mature MMP-2 enzyme. In sum, understanding of the structural requirements for the
      9E8 antibody specificity may pave the way for the focused design of the
      inhibitory antibodies against other individual MMPs. 

PMID- 24296750
TI  - Obesity and cardiovascular disease risk factors among the indigenous and
      immigrant Pakistani population: a systematic review.
AB  - AIM: The aim of this study was to systematically describe the gender and ethnic
      differences regarding the prevalence of general/central obesity and
      cardiovascular disease (CVD) risk factors such as diabetes mellitus type 2,
      hypertension, and hypercholesterolemia among the indigenous and immigrant
      Pakistani communities. METHODS: The search engine used was PubMed, supplemented
      with regional data from the Medical Institutes of Pakistan. The focus was on the
      adult Pakistani population (18 years and older). RESULTS: We found only 7 studies
      among the immigrant Pakistani community and 24 studies among the indigenous
      Pakistani community. The studies had limitations such as low participation rates
      and use of self-reported data. There is a higher prevalence of central obesity
      among women (42.2%) than among men (14.7%) (National Health Survey of Pakistan).
      Certain ethnicities such as Muhajir and Baluchis showed a higher prevalence of
      cardiovascular risk factors when compared to other ethnicities in the indigenous
      Pakistani population. The results also indicate that the prevalence of obesity is
      10-20% higher among the immigrant Pakistanis than in the indigenous Pakistanis.
      CONCLUSION: The relatively high prevalence of obesity and associated CVD risk
      factors (especially in women) among both indigenous and immigrant Pakistani
      populations require the attention of the healthcare professionals and policy
      makers, both inside and outside Pakistan.

PMID- 24296751
TI  - Autoantibodies as potential biomarkers for the early detection of esophageal
      squamous cell carcinoma.
AB  - OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent
      causes of cancer death worldwide and effective diagnosis is needed. We assessed
      the diagnostic potential of an autoantibody panel that may benefit early
      diagnosis. METHODS: We analyzed data for patients with ESCC and normal controls
      in a test cohort and a validation cohort. Autoantibody levels were measured
      against a panel of six tumor-associated antigens (p53, NY-ESO-1, matrix
      metalloproteinase-7 (MMP-7), heat shock protein 70 (Hsp70), peroxiredoxin VI (Prx
      VI), and BMI1 polycomb ring finger oncogene (Bmi-1)) by enzyme-linked
      immunosorbent assay. RESULTS: We assessed serum autoantibodies in 513
      participants: 388 with ESCC and 125 normal controls. The validation cohort
      comprised 371 participants: 237 with ESCC, and 134 normal controls.
      Autoantibodies to at least 1 of 6 antigens demonstrated a sensitivity/specificity
      of 57% (95% confidence interval (CI): 52-62%)/95% (95% CI: 89-98%) and 51% (95%
      CI: 45-57%)/96% (95% CI: 91-99%) in the test and validation cohorts,
      respectively. Measurement of the autoantibody panel could differentiate early
      stage ESCC patients from normal controls (sensitivity 45% (95% CI: 32-59%) and
      specificity 95% (95% CI: 89-98%) in the test cohort; 46% (95% CI: 35-58%) and 96%
      (95% CI: 91-99%) in the validation cohort). In either cohort, no significant
      differences were seen when patients were subdivided by age, gender, smoking
      status, size of tumor, site of tumor, depth of tumor invasion, histological
      grade, lymph node status, TNM stage, or early-stage and late-stage groups.
      CONCLUSIONS: Measurement of an autoantibody response to multiple tumor-associated
      antigens in an optimized panel assay, to help discriminate early-stage ESCC
      patients from normal controls, may aid in early detection of ESCC.

PMID- 24296753
TI  - Alu-mediated recombination defect in IGF1R: haploinsufficiency in a patient with
      short stature.
AB  - BACKGROUND: The insulin-like growth factor (IGF) receptor (IGF1R) is essential
      for normal development and growth. IGF1R mutations cause IGF-1 resistance
      resulting in intrauterine and postnatal growth failure. The phenotypic spectrum
      related to IGF1R mutations remains to be fully understood. METHODS: Auxological
      and endocrinological data of a patient identified previously were assessed. The
      patient's fibroblasts were studied to characterize the IGF1R deletion, mRNA fate,
      protein expression and signalling capabilities. RESULTS: The boy, who carries a
      heterozygous IGF1R exon 6 deletion caused by Alu element-mediated recombination
      and a heterozygous SHOX variant (p.Met240Ile), was born appropriate for
      gestational age but developed proportionate short stature postnatally. IGF-1
      levels were low-normal. None of the stigmata associated with SHOX deficiency or
      sporadically observed in IGF1R mutation carriers were present. Nonsense-mediated
      mRNA decay led to a substantial decline of IGF1R dosage and IGF-1-dependent
      receptor autophosphorylation but not impaired downstream signalling. CONCLUSION:
      We present the first detailed report of an intragenic IGF1R deletion identified
      in a patient who, apart from short stature, deviates from all established markers
      that qualify a growth-retarded child for IGF1R analysis. Although such children
      will usually escape routine clinical mutation screenings, they can contribute to
      the understanding of factors and mechanisms that cooperate with the IGF1R.

PMID- 24296754
TI  - Dynamic combinatorial/covalent chemistry: a tool to read, generate and modulate
      the bioactivity of compounds and compound mixtures.
AB  - Reversible covalent bond formation under thermodynamic control adds reactivity to
      self-assembled supramolecular systems, and is therefore an ideal tool to assess
      complexity of chemical and biological systems. Dynamic combinatorial/covalent
      chemistry (DCC) has been used to read structural information by selectively
      assembling receptors with the optimum molecular fit around a given template from
      a mixture of reversibly reacting building blocks. This technique allows access to
      efficient sensing devices and the generation of new biomolecules, such as small
      molecule receptor binders for drug discovery, but also larger biomimetic polymers
      and macromolecules with particular three-dimensional structural architectures.
      Adding a kinetic factor to a thermodynamically controlled equilibrium results in
      dynamic resolution and in self-sorting and self-replicating systems, all of which
      are of major importance in biological systems. Furthermore, the temporary
      modification of bioactive compounds by reversible combinatorial/covalent
      derivatisation allows control of their release and facilitates their transport
      across amphiphilic self-assembled systems such as artificial membranes or cell
      walls. The goal of this review is to give a conceptual overview of how the impact
      of DCC on supramolecular assemblies at different levels can allow us to
      understand, predict and modulate the complexity of biological systems. 

PMID- 24296752
TI  - In vivo diagnostic accuracy of high-resolution microendoscopy in differentiating
      neoplastic from non-neoplastic colorectal polyps: a prospective study.
AB  - OBJECTIVES: High-resolution microendoscopy (HRME) is a low-cost, "optical biopsy"
      technology that allows for subcellular imaging. The purpose of this study was to
      determine the in vivo diagnostic accuracy of the HRME for the differentiation of
      neoplastic from non-neoplastic colorectal polyps and compare it to that of high
      definition white-light endoscopy (WLE) with histopathology as the gold standard.
      METHODS: Three endoscopists prospectively detected a total of 171 polyps from 94
      patients that were then imaged by HRME and classified in real-time as neoplastic
      (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory).
      RESULTS: HRME had a significantly higher accuracy (94%), specificity (95%), and
      positive predictive value (PPV, 87%) for the determination of neoplastic
      colorectal polyps compared with WLE (65%, 39%, and 55%, respectively). When
      looking at small colorectal polyps (less than 10 mm), HRME continued to
      significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98%
      vs. 40%) and PPV (92% vs. 55%). These trends continued when evaluating diminutive
      polyps (less than 5 mm) as HRME's accuracy (95%), specificity (98%), and PPV
      (93%) were all significantly greater than their WLE counterparts (62%, 41%, and
      53%, respectively). CONCLUSIONS: In conclusion, this in vivo study demonstrates
      that HRME can be a very effective modality in the differentiation of neoplastic
      and non-neoplastic colorectal polyps. A combination of standard white-light
      colonoscopy for polyp detection and HRME for polyp classification has the
      potential to truly allow the endoscopist to selectively determine which lesions
      can be left in situ, which lesions can simply be discarded, and which lesions
      need formal histopathologic analysis.

PMID- 24296755
TI  - Effect of cations on condensation of a mesogenic amphiphilic molecule at the air
      aqueous electrolyte interface.
AB  - We report the interactions of a mesogenic molecule, 4'-octyl-4-biphenyl
      carbonitrile (8CB), with some cations (Na(+), Cu(2+), Ni(2+), La(3+) and Al(3+))
      dissolved in the aqueous subphase. Surface manometry studies show that the di-
      (Ni(2+) and Cu(2+)) and trivalent (La(3+)) ions promote condensation in the area
      per molecule and enhance the stability of the monolayer. This is inferred from
      the increase in the values of collapse pressure and the compression elastic
      modulus. The specific ion effect is seen between perchlorate and chloride anions
      with respect to the Al(3+) cation. The presence of monovalent ions (Na(+)) in the
      subphase does not influence the isotherm of 8CB. However, in this case, with pH
      (>6), the isotherm shifts to a higher area per molecule. The excess Gibbs free
      energy calculated for the 8CB monolayer indicates repulsive interaction for
      monovalent ions and attractive interaction for multivalent ions in the subphase.
      Kinetic studies of the monolayer in an ion-enriched subphase have yielded an
      additional characteristic time constant indicative of reorganization of the
      monolayer. Ellipsometric adsorption isotherm measurements carried out for
      representative ions show a reduction in the value of the ellipsometric angle with
      increasing valency. Our studies indicate that the interaction of ions with the
      8CB monolayer at the air-electrolyte interface can be promoted by choosing
      cations of higher valency and anions of larger size, higher polarizability and
      chaotropic nature. These factors play an important role and can potentially
      affect the anchoring transition. 

PMID- 24296757
TI  - Inhibition of PP2A activity confers a TRAIL-sensitive phenotype during malignant
      transformation.
AB  - TRAIL is a promising anticancer agent because it induces apoptosis in the
      majority of human cancer cells but spares the normal cells. To determine the
      mechanistic nature of how normal cells acquire a TRAIL-sensitive phenotype during
      the process of malignant transformation, an experimental cell system was
      developed by sequential introduction of human telomerase reverse transcriptase
      and SV40 T antigens (large and small) into normal human prostatic epithelial
      cells (PrEC). This model system demonstrated that inhibition of protein
      phosphatase 2A (PP2A), either by SV40 small T antigen, okadaic acid, Calyculin A,
      or PP2A catalytic subunit siRNA, sensitized normal human PrEC and immortalized
      cells to TRAIL-induced apoptosis. Moreover, sensitization occurred during the
      premalignant period of tumorigenesis and PP2A exerted its antiapoptotic activity
      by negatively regulating c-Fos/AP-1. In addition, low-dose okadaic acid treatment
      sensitized TRAIL-resistant cancer cells to TRAIL, suggesting that PP2A inhibitors
      could be used as an enhancer of apoptosis induced by TRAIL or TRAIL-like agents.
      These data indicate that downregulation of PP2A activity is a critical step for
      normal cells to acquire a TRAIL-sensitive phenotype during tumorigenesis and that
      the level of PP2A activity may foretell cellular sensitivity to TRAIL-induced
      apoptosis. IMPLICATIONS: Inhibition of PP2A is a key determinant in acquiring
      TRAIL sensitivity during tumorigenesis, with c-Fos/AP-1 as an essential mediator.

PMID- 24296756
TI  - Autophagy-dependent metabolic reprogramming sensitizes TSC2-deficient cells to
      the antimetabolite 6-aminonicotinamide.
AB  - The mammalian target of rapamycin complex 1 (mTORC1) is hyperactive in many human
      cancers and in tuberous sclerosis complex (TSC). Autophagy, a key mTORC1-targeted
      process, is a critical determinant of metabolic homeostasis. Metabolomic
      profiling was performed to elucidate the cellular consequences of autophagy
      dysregulation under conditions of hyperactive mTORC1. It was discovered that TSC2
      null cells have distinctive autophagy-dependent pentose phosphate pathway (PPP)
      alterations. This was accompanied by enhanced glucose uptake and utilization,
      decreased mitochondrial oxygen consumption, and increased mitochondrial reactive
      oxygen species (ROS) production. Importantly, these findings revealed that the
      PPP is a key autophagy-dependent compensatory metabolic mechanism. Furthermore,
      PPP inhibition with 6-aminonicotinamide (6-AN) in combination with autophagy
      inhibition suppressed proliferation and prompted the activation of NF-kappaB and
      CASP1 in TSC2-deficient, but not TSC2-proficient cells. These data demonstrate
      that TSC2-deficient cells can be therapeutically targeted, without mTORC1
      inhibitors, by focusing on their metabolic vulnerabilities. IMPLICATIONS: This
      study provides proof-of-concept that therapeutic targeting of diseases with
      hyperactive mTORC1 can be achieved without the application of mTORC1 inhibitors.

PMID- 24296758
TI  - ROS1 and ALK fusions in colorectal cancer, with evidence of intratumoral
      heterogeneity for molecular drivers.
AB  - Activated anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases, through
      gene fusions, have been found in lung adenocarcinomas and are highly sensitive to
      selective kinase inhibitors. This study aimed at identifying the presence of
      these rearrangements in human colorectal adenocarcinoma specimens using a 4
      target, 4-color break-apart FISH assay to simultaneously determine the genomic
      status of ALK and ROS1. Among the clinical colorectal cancer specimens analyzed,
      rearrangement-positive cases for both ALK and ROS1 were observed. The fusion
      partner for ALK was identified as EML4 and the fusion partner for one of the ROS1
      positive cases was SLC34A2, the partner for the other ROS1-positive case remains
      to be identified. A small fraction of specimens presented duplicated or clustered
      copies of native ALK and ROS1. In addition, rearrangements were detected in
      samples that also harbored KRAS and BRAF mutations in two of the three cases.
      Interestingly, the ALK-positive specimen displayed marked intratumoral
      heterogeneity and rearrangement was also identified in regions of high-grade
      dysplasia. Despite the additional oncogenic events and tumor heterogeneity
      observed, elucidation of the first cases of ROS1 rearrangements and confirmation
      of ALK rearrangements support further evaluation of these genomic fusions as
      potential therapeutic targets in colorectal cancer. IMPLICATIONS: ROS1 and ALK
      fusions occur in colorectal cancer and may have substantial impact in therapy
      selection.

PMID- 24296760
TI  - Ag+ insertion into 3D hierarchical rose-like Cu(1.8)Se nanocrystals with tunable
      band gap and morphology genetic.
AB  - In this study, novel hierarchical rose-like Cu1.8Se microspheres with a porous
      three-dimensional (3D) framework were successfully synthesized by using a one-pot
      in situ growth method at low temperature (60  degrees C). The Cu1.8Se
      microspheres covered the surface of the 3D porous framework. The formation
      mechanism was investigated in detail by adjusting the volume ratio of DMF and
      EDA, as the blend solvents, and the reaction time. Then, the chemical composition
      of the Cu1.8Se microspheres was altered by Ag(+) exchange without changing their
      morphology and structure. In this way, the binary Cu1.8Se was efficiently
      converted into the ternary CuAgSe. Notably, the band gap of materials was tuned
      continuously from 3.83 eV to 3.03 eV, and CuAgSe was produced continuously by
      adjusting the replacement time. This work provides a novel concept and a simple
      method that can serve as a good reference for improving the performance of
      tunable materials and the preparation of multielement alloy materials. 

PMID- 24296759
TI  - Loss of the nucleosome-binding protein HMGN1 affects the rate of N
      nitrosodiethylamine-induced hepatocarcinogenesis in mice.
AB  - We report that HMGN1, a nucleosome-binding protein that affects chromatin
      structure and function, affects the growth of N-nitrosodiethylamine (DEN)-induced
      liver tumors. Following a single DEN injection at 2 weeks of age, Hmgn1(tm1/tm1)
      mice, lacking the nucleosome-binding domain of HMGN1, had earlier signs of liver
      tumorigenesis than their Hmgn1(+/+) littermates. Detailed gene expression
      profiling revealed significant differences between DEN-injected and control
      saline-injected mice, but only minor differences between the injected
      Hmgn1(tm1/tm1) mice and their Hmgn1(+/+) littermates. Pathway analysis revealed
      that the most significant process affected by loss of HMGN1 involves the
      lipid/sterol metabolic pathway. Our study indicates that in mice, loss of HMGN1
      leads to transcription changes that accelerate the progression of DEN-induced
      hepatocarcinogenesis, without affecting the type of tumors or the final total
      tumor burden of these mice. IMPLICATIONS: Loss of HMGN1 leads to accelerated
      progression of DEN-induced hepatocarcinogenesis in mice.

PMID- 24296761
TI  - Etomidate use and postoperative outcomes among cardiac surgery patients.
AB  - BACKGROUND: Although a single dose of etomidate can cause relative adrenal
      insufficiency, the impact of etomidate exposure on postoperative outcomes is
      unknown. The objective of this study was to examine the association between a
      single induction dose of etomidate and clinically important postoperative
      outcomes after cardiac surgery. METHODS: The authors retrospectively examined the
      association between etomidate exposure during induction of anesthesia and
      postoperative outcomes in patients undergoing cardiac surgery from January 2007
      to December 2009 by using multivariate logistic regression analyses and Cox
      proportional hazards regression analyses. Postoperative outcomes of interest were
      severe hypotension, mechanical ventilation hours, hospital length of stay, and in
      hospital mortality. RESULTS: Sixty-two percent of 3,127 patients received
      etomidate. Etomidate recipients had a higher incidence of preoperative congestive
      heart failure (23.0 vs. 18.3%; P = 0.002) and a lower incidence of preoperative
      cardiogenic shock (1.3 vs. 4.0%; P < 0.001). The adjusted odds ratio for severe
      hypotension and in-hospital mortality associated with receiving etomidate was
      0.80 (95% CI, 0.58-1.09) and 0.75 (95% CI, 0.45-1.24), respectively, and the
      adjusted hazard ratio for time to mechanical ventilation removal and time to
      hospital discharge was 1.10 (95% CI, 1.00-1.21) and 1.07 (95% CI, 0.97-1.18),
      respectively. Propensity score analysis did not change the association between
      etomidate use and postoperative outcomes. CONCLUSIONS: In this study, there was
      no evidence to suggest that etomidate exposure was associated with severe
      hypotension, longer mechanical ventilation hours, longer length of hospital stay,
      or in-hospital mortality. Etomidate should remain an option for induction of
      anesthesia in cardiac surgery patients.

PMID- 24296762
TI  - Nociceptor-selective peripheral nerve block induces delayed mechanical
      hypersensitivity and neurotoxicity in rats.
AB  - BACKGROUND: Long-lasting, sensory-specific peripheral nerve blockade would
      advance perioperative analgesia. Perineural injection of a combination of
      transient receptor potential vanilloid 1 channel agonists and lidocaine or its
      hydrophilic derivative, QX-314, produces prolonged sensory or nociceptor
      selective nerve block in rodents. In this study, the authors tested the efficacy
      of these combinations in peripheral nerve block after incisional surgery in rats.
      METHODS: The authors administered perisciatic lidocaine (2%), QX-314 (0.2%)
      followed by dilute capsaicin (0.05%, 10 min later), or vehicle in rats and the
      duration of motor and sensory block to thermal and mechanical stimuli assessed in
      normal animals and those after incisional surgery to the hind paw. Other animals
      receiving these injections were evaluated 7 weeks later by behavior and histology
      for potential neurotoxicity. RESULTS: Perineural injection of the combination not
      only attenuated mechanical hypersensitivity for 72 h after incision but also
      resulted in delayed onset mechanical hypersensitivity several weeks later,
      accompanied by degeneration of central terminals of isolectin B4 (nonpeptidergic)
      and calcitonin gene-related peptide-containing (peptidergic) afferents in the
      ipsilateral spinal cord. Dorsal root ganglia ipsilateral to injection of the
      combination showed increased expression of activating transcription factor-3 and
      satellite cell activation. CONCLUSIONS: Combined administration of local
      anesthetics with the transient receptor potential vanilloid 1 agonist capsaicin
      induced a near complete blockade of incision-induced hypersensitivity for several
      days. However, the same combination induced delayed mechanical hypersensitivity
      and neurotoxicity in naive rats. Combination of these drugs in these
      concentrations is likely to result in neurotoxicity, and the safety of other
      concentrations warrants further study.

PMID- 24296763
TI  - Cardiac resuscitation and coagulation.

PMID- 24296764
TI  - Bubble bursting as an aerosol generation mechanism during an oil spill in the
      deep-sea environment: molecular dynamics simulations of oil alkanes and
      dispersants in atmospheric air/salt water interfaces.
AB  - Potential of mean force (PMF) calculations and molecular dynamics (MD)
      simulations were performed to investigate the properties of oil n-alkanes [i.e.,
      n-pentadecane (C15), n-icosane (C20) and n-triacontane (C30)], as well as several
      surfactant species [i.e., the standard anionic surfactant sodium dodecyl sulfate
      (SDS), and three model dispersants similar to the Tween and Span species present
      in Corexit 9500A] at air/salt water interfaces. This study was motivated by the
      2010 Deepwater Horizon (DWH) oil spill, and our simulation results show that,
      from the thermodynamic point of view, the n-alkanes and the model dispersants
      have a strong preference to remain at the air/salt water interface, as indicated
      by the presence of deep free energy minima at these interfaces. The free energy
      minimum of these n-alkanes becomes deeper as their chain length increases, and as
      the concentration of surfactant species at the interface increases. The n-alkanes
      tend to adopt a flat orientation and form aggregates at the bare air/salt water
      interface. When this interface is coated with surfactants, the n-alkanes tend to
      adopt more tilted orientations with respect to the vector normal to the
      interface. These simulation results are consistent with the experimental findings
      reported in the accompanying paper [Ehrenhauser et al., Environ. Sci.: Processes
      Impacts 2013, in press, (DOI: 10.1039/c3em00390f)]. The fact that these long
      chain n-alkanes show a strong thermodynamic preference to remain at the air/salt
      water interfaces, especially if these interfaces are coated with surfactants,
      makes these species very likely to adsorb at the surface of bubbles or droplets
      and be ejected to the atmosphere by sea surface processes such as whitecaps
      (breaking waves) and bubble bursting. Finally, the experimental finding that more
      oil hydrocarbons are ejected when Corexit 9500A is present in the system is
      consistent with the deeper free energy minima observed for the n-alkanes at the
      air/salt water interface at increasing concentrations of surfactant species. 

PMID- 24296765
TI  - Novel use of rituximab for steroid-dependent nephrotic syndrome in children.
AB  - BACKGROUND: Though rituximab (RTX) is effective for childhood steroid-dependent
      nephrotic syndrome (SDNS), an established regimen does not exist. The relapses
      tend to occur when the peripheral blood B-cell count re-arises at 3 months upon
      single RTX infusion. This study was conducted to clarify whether the long-term
      remission of SDNS can be obtained by repeated RTX administrations. METHODS: RTX
      was administered 4 times at 3-month intervals at 375 mg/m(2)/time to 5 children
      with SDNS. The changes in the clinical indicators were analyzed. RESULTS: The
      median (range) observation period was 6.3 (0.9-8.4) years before RTX and 3.2 (1.9
      3.8) years following the commencement of RTX. The changes in the clinical
      indicators were as follows (median and range): (1) annual number of relapses:
      before administration 1.4 (1.1-3.5) times/year, after administration 0.0 (0.0
      0.0) times/year, and (2) median steroid dosage: before administration 0.80 (0.23
      0.96) mg/kg/day, after administration 0.00 (0.00-0.00) mg/kg/day. All changes
      were significant at p < 0.05. Relapse occurred 3 times following the start of RTX
      (the period to relapse was 2.2, 1.9, and 2.3 years, respectively). No serious
      side effects were seen. CONCLUSIONS: Repeated RTX against SDNS in children may be
      a useful therapeutic option.

PMID- 24296766
TI  - The low hepatic toxicity per Gray of 90Y glass microspheres is linked to their
      transport in the arterial tree favoring a nonuniform trapping as observed in
      posttherapy PET imaging.
AB  - (90)Y resin and glass microsphere liver radioembolizations delivering lobar doses
      of 70 and 120 Gy, respectively, display hepatic toxicity similar to 40-Gy
      fractionated external-beam radiotherapy. We investigated how the lower number of
      glass microspheres could induce a sufficiently nonuniform dose distribution
      explaining this paradox. METHODS: Microscale dosimetry was assessed in the
      realistic liver model developed by Gulec et al. but using the Russell's dose
      deposition kernel. A lattice of hexagonal prisms represented the hepatic lobules.
      Two hepatic arterial tree models-that is, a fixed-length and a variable-branches
      length-were used for the microsphere transport. Equal or asymmetric microsphere
      relative-spreading probability between 2 daughter vessels was assumed. Several
      120-Gy liver simulations were performed: periodic simulations, where 1 or 6 glass
      microspheres were trapped in all and in only 1 of 6 portal tracts, respectively,
      and random simulations, where glass microsphere trapping assumed an equal
      probability for all the portal tracts or a variable probability depending on the
      successions of artery connections leading to the portal tract, both for the 2
      arterial tree models. RESULTS: For the 2 uniform simulations, all hepatic
      structures received at least 100 Gy. The fast decrease of the (90)Y kernel as the
      inverse of the square of the distance r is counterbalanced by the number of
      contributing lobules containing microspheres that increases as r(2). The random
      simulation with equal-spreading probability gave for the less irradiated tissue a
      lobule dose distribution centered around 103 Gy (full width at half maximum, 20
      Gy). The distribution became significantly asymmetric with the 60%-40% relative
      spreading probability, with a shift of the maximum from 103 down to 50 Gy, and
      about 17% of the lobules got a dose lower than 40 Gy to their different
      structures. CONCLUSION: The large nonuniform trapping produced by the microsphere
      transport in the arterial tree jointly with the low number of injected glass
      microspheres begins to explain their lower hepatic toxicity per Gray. In
      addition, the nonuniform trapping supports the fact that the granular aspect of
      (90)Y PET imaging observed in patients could represent some reality and not only
      statistical noise.

PMID- 24296767
TI  - Coronary artery bypass grafting vs percutaneous coronary intervention and long
      term mortality and morbidity in multivessel disease: meta-analysis of randomized
      clinical trials of the arterial grafting and stenting era.
AB  - IMPORTANCE: Recent trials of percutaneous coronary intervention (PCI) vs coronary
      artery bypass grafting (CABG) for multivessel disease were not designed to detect
      a difference in mortality and therefore were underpowered for this outcome.
      Consequently, the comparative effects of these 2 revascularization methods on
      long-term mortality are still unclear. In the absence of solid evidence for
      mortality difference, PCI is oftentimes preferred over CABG in these patients,
      given its less invasive nature. OBJECTIVES: To determine the comparative effects
      of CABG vs PCI on long-term mortality and morbidity by performing a meta-analysis
      of all randomized clinical trials of the current era that compared the 2
      treatment techniques in patients with multivessel disease. DATA SOURCES: A
      systematic literature search was conducted for all randomized clinical trials
      directly comparing CABG with PCI. STUDY SELECTION: To reflect current practice,
      we included randomized trials with 1 or more arterial grafts used in at least
      90%, and 1 or more stents used in at least 70% of the cases that reported
      outcomes in patients with multivessel disease. DATA EXTRACTION: Numbers of events
      at the longest possible follow-up and sample sizes were extracted. DATA
      SYNTHESIS: A total of 6 randomized trials enrolling a total of 6055 patients were
      included, with a weighted average follow-up of 4.1 years. There was a significant
      reduction in total mortality with CABG compared with PCI (I2 = 0%; risk ratio
      [RR], 0.73 [95% CI, 0.62-0.86]) (P < .001). There were also significant
      reductions in myocardial infarction (I2 = 8.02%; RR, 0.58 [95% CI, 0.48-0.72]) (P
      < .001) and repeat revascularization (I2 = 75.6%; RR, 0.29 [95% CI, 0.21-0.41])
      (P < .001) with CABG. There was a trend toward excess strokes with CABG (I2 =
      24.9%; RR, 1.36 [95% CI, 0.99-1.86]), but this was not statistically significant
      (P = .06). For reduction in total mortality, there was no heterogeneity between
      trials that were limited to and not limited to patients with diabetes or whether
      stents were drug eluting or not. Owing to lack of individual patient-level data,
      additional subgroup analyses could not be performed. CONCLUSIONS AND RELEVANCE:
      In patients with multivessel coronary disease, compared with PCI, CABG leads to
      an unequivocal reduction in long-term mortality and myocardial infarctions and to
      reductions in repeat revascularizations, regardless of whether patients are
      diabetic or not. These findings have implications for management of such
      patients.

PMID- 24296768
TI  - Water-soluble noncovalent adducts of the heterometallic copper subgroup complexes
      and human serum albumin with remarkable luminescent properties.
AB  - Novel water-soluble noncovalent adducts of the heterometallic copper subgroup
      complexes and human serum albumin (HSA) display strong phosphorescence,
      internalize into HeLa cells and can be used in time-resolved fluorescent imaging.

PMID- 24296770
TI  - Pneumothorax occurring after nasogastric tube removal.
AB  - An 85-year-old woman with failure to thrive due to poor oral intake was admitted
      owing to dehydration. A nasogastric (NG) tube was inserted for the initiation of
      enteral feedings. The tube position was confirmed by gastric auscultation after
      insufflating air through the tube. A chest X-ray revealed that the NG tube
      traversed the right main stem bronchus with its tip ending in the right
      costophrenic angle adjacent to the pleura. No pneumothorax was identified. The
      tube was removed and a short while later the patient developed mild chest
      discomfort. A repeat chest X-ray revealed significant pneumothorax on the right
      side. She was treated conservatively with 100% oxygen with successful resolution
      of the pneumothorax.

PMID- 24296771
TI  - Mixed dust pneumoconiosis occurring in an unusual setting.
AB  - Mixed dust pneumoconiosis secondary to domestic wood smoke exposure is a cause of
      pneumoconiosis in women from developing countries, but is rarely seen in the USA.
      An elderly female non-smoker, who immigrated to the USA from Pakistan 10 years
      previously, presented with a worsening non-productive cough and dyspnoea on
      exertion. She did not have any occupational or environmental exposures other than
      utilising firewood for cooking while living in Pakistan. Radiographs revealed
      multiple bilateral pulmonary nodules associated with hilar and mediastinal
      adenopathy. A video-assisted thoracoscopic biopsy revealed ill-defined nodules in
      a perivascular subpleural deposition, carbon pigment deposition around the
      terminal bronchioles, dust macules and negatively birefringent needles on
      polarised light microscopy with mixed dust nodules outnumbering the silicotic
      nodules consistent with mixed dust pneumoconiosis. This case illustrates the need
      for awareness of this condition among physicians caring for women who lived in
      areas where biomass exposure is common. 

PMID- 24296772
TI  - Ophthalmoplegic migraine with isolated third cranial nerve palsy in a known case
      of juvenile myoclonic epilepsy.
AB  - Among the various forms of migraine headaches, ophthalmoplegic migraine is an
      uncommon and rare form, the incidence of which is approximately 0.7 per million.
      It presents predominantly with headache and ophthalmoplegia. One of more cranial
      nerves can be affected, however the third cranial nerve is most often affected.
      As a result, symptoms wise, mydriasis and ptosis are commonly seen. Patients
      generally recover completely within a few days or weeks, however residual
      deficits are known to occur in a minority of patients. One of the common
      generalised epilepsy syndromes is the juvenile myoclonic epilepsy (JME), its
      prevalence being roughly up to 10% of all patients with epilepsy. It usually
      begins in the second decade of life. Generalised tonic-clonic seizures myoclonic
      jerks absences constitute the main seizure types in JME. Studies indicate a
      definite association of epilepsy with migraine headaches and a significant number
      of migraneurs are found to be epileptic. Conversely, patients with epilepsy are
      two times more likely to have migraine, as compared to their first degree
      relatives without migraine. We report a known case of a female patient of JME
      having a history of classical migraine with aura presenting to us with headache
      and ophthalmoplegia. She was extensively evaluated to rule out other causes of
      isolated third cranial nerve palsy, with all the investigations being negative
      for any obvious cause. She was treated with non-steroidal anti-inflammatory drugs
      for the acute attack and was subsequently put on antimigraine medication,
      propranolol during her hospital stay, with which her ptosis recovered completely
      after 2 weeks. The patient was later started on tablet divalproex sodium, which
      the patient continues to take on a long-term basis, especially because of its
      efficacy as an antimigraine prophylaxis agent and a potent drug against JME. 

PMID- 24296773
TI  - Metastatic squamous cell carcinoma urinary bladder coexisting with tuberculosis
      in pelvic lymph nodes.
AB  - Squamous cell carcinoma (SCC) of the urinary bladder is usually associated with
      Schistosoma haematobium and chronic bladder irritation. We report a case of
      coexistent metastatic SCC and tuberculosis in obturator lymph nodes in radical
      cystoprostatectomy and pelvic lymphadenectomy specimens. Though tubercular iliac
      lymphadenitis and metastatic transitional carcinoma following intravesical BCG
      has been reported, the concurrent presence of non-transitional cell cancer and
      primary lymph nodal tuberculosis in regional lymph nodes is rare. This case is
      reported to highlight the paucity of management guidelines available presently in
      the treatment of such patients who require systemic chemotherapy and
      antitubercular therapy. 

PMID- 24296774
TI  - Anterior tumors of the prostate: clinicopathological features and outcomes.
AB  - BACKGROUND: To determine whether prostate cancers detected in the anterior vs
      posterior zones impact clinicopathological features and patient outcomes. This
      information could potentially affect clinical management. METHODS: A
      retrospective pathological review of 1528 radical prostatectomy specimens
      submitted between 1989 and 2011 was completed. Specimens were characterized as
      anterior zone vs posterior zone based on index tumor and predominant tumor volume
      location. The chi-square test was used to determine associations between tumor
      location and categorical patient features. Kaplan-Meier unadjusted analysis was
      used to compare biochemical recurrence-free and overall survival. RESULTS: Tumors
      occurred predominantly in the anterior location in 155 (10.1%) of specimens.
      There was no difference between mean age, body mass index, racial distribution,
      family history, number of previous biopsies, clinical Gleason sum or pathological
      stage in the two groups. Fewer patients had clinically palpable disease in the
      anterior tumor group, 28.8% vs 40.7% (P=0.0150). Pretreatment PSA was lower in
      the anterior tumor group. Total tumor volume did differ with anterior tumors
      having a mean 8.3 cc vs 5.6 cc (P<0.0001) size and a higher incidence of positive
      margins (P=0.0008). There were no differences in biochemical recurrence-free or
      overall survival. CONCLUSIONS: Despite the potential for adverse pathological
      features in anterior-based disease, there appears to be no demographic
      predilection, notable delay in diagnosis or significant difference in survival
      outcomes.

PMID- 24296775
TI  - A two-dimensional hydrogen bonded organic framework self-assembled from a three
      fold symmetric carbamate.
AB  - A flexible organic sheet spontaneously assembled under mild conditions from a tri
      carbamate. By introducing cyclohexyl side chains as 'pillars' between the sheets,
      a hydrogen bonded organic framework was formed which displayed a capacity for
      accommodating and releasing guest molecules. The guest size/shape selectivity of
      the lamellar framework was demonstrated by testing with various guests. 

PMID- 24296776
TI  - Antithrombin III supplementation on extracorporeal membrane oxygenation: impact
      on heparin dose and circuit life.
AB  - Antithrombin III (ATIII) is used during extracorporeal membrane oxygenation
      (ECMO) based on physiologic rationale and studies during cardiopulmonary bypass.
      In February 2008, our institution began using ATIII as replacement for low ATIII
      activity (<70%) in patients supported with ECMO. We hypothesized that ATIII
      supplementation would reduce heparin infusion rates, increase unfractionated
      heparin anti-Xa levels, and prolong ECMO circuit life. Data from 40 consecutive
      patients (45 deployments) requiring ECMO support for >72 hours with venoarterial
      ECMO from January 1, 2007, through December 31, 2008, were collected.
      Antithrombin III concentrate was administered for ATIII activity <70% at the
      discretion of the attending physician. The primary outcome was whether the
      heparin infusion rate was reduced by 10% or more as a result of ATIII
      administration. No difference in heparin infusion rate (p = 0.245) as a result of
      ATIII administration was observed. Anti-Xa levels were lower before ATIII
      administration (p< 0.001) and were increased after ATIII administration (p <
      0.001). There was an increased frequency of circuit failure in ATIII treatment
      group compared with nontreatment group (p = 0.018). Neither heparin
      responsiveness nor circuit life was enhanced by daily ATIII supplementation for
      activity <70%. Future studies are warranted to evaluate the effectiveness of
      antithrombin replacement. 

PMID- 24296777
TI  - The benefits of pulsatile machine perfusion of standard criteria deceased donor
      kidneys at a geographically remote transplant center.
AB  - Benefits of pulsatile machine perfusion (pumping) of standard criteria donor
      (SCD) kidneys are unclear. Our center is located 41/2 hours from our Organ
      Procurement Organization. We evaluated outcomes of pumping SCD kidneys under such
      circumstances by conducting a retrospective examination of all SCD kidneys
      transplanted between January 2007 and March 2012, comparing kidneys pumped (28
      [group 1]) versus standard cold storage (77 [group 2]). Group 1 had fewer delayed
      graft function (DGF, 3.57% vs. 23.38%, p = 0.02) and slow graft function (SGF,
      7.14% vs. 24.68%; p = 0.047) and faster serum creatinine recovery curve (p <
      0.001) than group 2. Having a kidney pumped decreases the incidence (odds ratio
      [OR], 0.059) of DGF, SGF, or primary nonfunction. Group 1 were quicker to reach
      an estimated glomerular filtration rate (eGFR) >30 ml/min (OR, 4.186; confidence
      interval [CI], [2.448-7.157]) or an eGFR >60 ml/min (OR, 2.669; CI [1.255
      5.679]). Pumping the SCD kidneys in a geographically remote transplant center
      tended to be better than those preserved in cold storage. However, except
      recovery curve of serum creatinine during the first postoperative month, other
      parameters failed to reach statistical significance in the post hoc examination
      of the contemporary groups. Prospective paired kidney study is required to
      scrutinize this finding. 

PMID- 24296778
TI  - Field-testing a new directional passive air sampler for fugitive dust in a
      complex industrial source environment.
AB  - Quantifying the sources of fugitive dusts on complex industrial sites is
      essential for regulation and effective dust management. This study applied two
      recently-patented Directional Passive Air Samplers (DPAS) to measure the fugitive
      dust contribution from a Metal Recovery Plant (MRP) located on the periphery of a
      major steelworks site. The DPAS can collect separate samples for winds from
      different directions (12 * 30 degrees  sectors), and the collected dust may be
      quantified using several different measurement methods. The DPASs were located up
      and down-prevailing-wind of the MRP processing area to (i) identify and measure
      the contribution made by the MRP processing operation; (ii) monitor this
      contribution during the processing of a particularly dusty material; and (iii)
      detect any changes to this contribution following new dust-control measures.
      Sampling took place over a 12-month period and the amount of dust was quantified
      using photographic, magnetic and mass-loading measurement methods. The DPASs are
      able to effectively resolve the incoming dust signal from the wider steelworks
      complex, and also different sources of fugitive dust from the MRP processing
      area. There was no confirmable increase in the dust contribution from the MRP
      during the processing of a particularly dusty material, but dust levels
      significantly reduced following the introduction of new dust-control measures.
      This research was undertaken in a regulatory context, and the results provide a
      unique evidence-base for current and future operational or regulatory decisions. 

PMID- 24296780
TI  - Generating rats with conditional alleles using CRISPR/Cas9.

PMID- 24296779
TI  - Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated
      phosphorylation of cortactin in hepatocellular carcinoma.
AB  - We have previously identified 1 241 regions of somatic copy number alterations
      (CNAs) in hepatocellular carcinoma (HCC). In the present study, we found that a
      novel recurrent focal amplicon, 1q24.1-24.2, targets the MPZL1 gene in HCC.
      Notably, there is a positive correlation between the expression levels of MPZL1
      and intrahepatic metastasis of the HCC specimens. MPZL1 can significantly enhance
      the migratory and metastatic potential of the HCC cells. Moreover, we found that
      one of the mechanisms by which MPZL1 promotes HCC cell migration is by inducing
      the phosphorylation and activation of the pro-metastatic protein, cortactin.
      Additionally, we found that Src kinase mediates the phosphorylation and
      activation of cortactin induced by MPZL1 overexpression. Taken together, these
      findings suggest that MPZL1 is a novel pro-metastatic gene targeted by a
      recurrent region of copy number amplification at 1q24.1-24.2 in HCC. 

PMID- 24296781
TI  - Identification of IFN-gamma-producing innate B cells.
AB  - Although B cells play important roles in the humoral immune response and the
      regulation of adaptive immunity, B cell subpopulations with unique phenotypes,
      particularly those with non-classical immune functions, should be further
      investigated. By challenging mice with Listeria monocytogenes, Escherichia coli,
      vesicular stomatitis virus and Toll-like receptor ligands, we identified an
      inducible CD11a(hi)FcgammaRIII(hi) B cell subpopulation that is significantly
      expanded and produces high levels of IFN-gamma during the early stage of the
      immune response. This subpopulation of B cells can promote macrophage activation
      via generating IFN-gamma, thereby facilitating the innate immune response against
      intracellular bacterial infection. As this new subpopulation is of B cell origin
      and exhibits the phenotypic characteristics of B cells, we designated these cells
      as IFN-gamma-producing innate B cells. Dendritic cells were essential for the
      inducible generation of these innate B cells from the follicular B cells via
      CD40L-CD40 ligation. Increased Bruton's tyrosine kinase activation was found to
      be responsible for the increased activation of non-canonical NF-kappaB pathway in
      these innate B cells after CD40 ligation, with the consequent induction of
      additional IFN-gamma production. The identification of this new population of
      innate B cells may contribute to a better understanding of B cell functions in
      anti-infection immune responses and immune regulation. 

PMID- 24296782
TI  - You are what you eat: multifaceted functions of autophagy during C. elegans
      development.
AB  - Autophagy involves the sequestration of a portion of the cytosolic contents in an
      enclosed double-membrane autophagosomal structure and its subsequent delivery to
      lysosomes for degradation. Autophagy activity functions in multiple biological
      processes during Caenorhabditis elegans development. The basal level of autophagy
      in embryos removes aggregate-prone proteins, paternal mitochondria and spermatid
      specific membranous organelles (MOs). Autophagy also contributes to the efficient
      removal of embryonic apoptotic cell corpses by promoting phagosome maturation.
      During larval development, autophagy modulates miRNA-mediated gene silencing by
      selectively degrading AIN-1, a component of miRNA-induced silencing complex, and
      thus participates in the specification of multiple cell fates controlled by
      miRNAs. During development of the hermaphrodite germline, autophagy acts
      coordinately with the core apoptotic machinery to execute genotoxic stress
      induced germline cell death and also cell death when caspase activity is
      partially compromised. Autophagy is also involved in the utilization of lipid
      droplets in the aging process in adult animals. Studies in C. elegans provide
      valuable insights into the physiological functions of autophagy in the
      development of multicellular organisms. 

PMID- 24296783
TI  - Small molecules enable OCT4-mediated direct reprogramming into expandable human
      neural stem cells.

PMID- 24296785
TI  - Molecule-based magnetic coolers.
AB  - There has been a rapid expansion in the use of molecular magnets for both low-
      and ultra low-temperature cooling applications in recent years, and here we
      review the chemical variation and magnetothermal properties of reported molecular
      coolers, structuring the review by structural dimensions, metal-ions involved and
      ligands employed. This review provides an overview of the developments in
      designing better low-temperature magnetic refrigerants, and includes description
      of new 3D-materials that, in some ways, out-perform traditional magnetic
      coolants. Thus, this review should serve as both a tutorial for many newcomers
      and a summary of progress for researchers who are active in the field. 

PMID- 24296784
TI  - A current perspective of autophagosome biogenesis.
AB  - Autophagy is a bulk degradation system induced by cellular stresses such as
      nutrient starvation. Its function relies on the formation of double-membrane
      vesicles called autophagosomes. Unlike other organelles that appear to stably
      exist in the cell, autophagosomes are formed on demand, and once their formation
      is initiated, it proceeds surprisingly rapidly. How and where this dynamic
      autophagosome formation takes place has been a long-standing question, but the
      discovery of Atg proteins in the 1990's significantly accelerated our
      understanding of autophagosome biogenesis. In this review, we will briefly
      introduce each Atg functional unit in relation to autophagosome biogenesis, and
      then discuss the origin of the autophagosomal membrane with an introduction to
      selected recent studies addressing this problem. 

PMID- 24296786
TI  - Cellulose biosynthesis: counting the chains.

PMID- 24296787
TI  - The sitting height/height ratio for age in healthy and short individuals and its
      potential role in selecting short children for SHOX analysis.
AB  - AIMS: To determine the presence of abnormal body proportion, assessed by sitting
      height/height ratio for age and sex (SH/H SDS) in healthy and short individuals,
      and to estimate its role in selecting short children for SHOX analysis. METHODS:
      Height, sitting height and weight were evaluated in 1,771 healthy children, 128
      children with idiopathic short stature (ISS), 58 individuals with SHOX defects
      (SHOX-D) and 193 females with Turner syndrome (TS). RESULTS: The frequency of
      abnormal body proportion, defined as SH/H SDS >2, in ISS children was 16.4% (95%
      CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p < 0.001).
      The SHOX gene was evaluated in all disproportionate ISS children and defects in
      this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95%
      CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS >2
      were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20
      36%) with TS. CONCLUSION: Abnormal body proportions were observed in almost all
      individuals with SHOX-D, 50% of females with TS and 16% of children considered
      ISS. Defects in SHOX gene were identified in 19% of ISS children with SH/H SDS
      >2, suggesting that SH/H SDS is a useful tool to select children for undergoing
      SHOX molecular studies.

PMID- 24296788
TI  - Partial liver resection because of bile duct injury.
AB  - AIM: To analyze the outcome of partial liver resection (PHx) after bile duct
      injury (BDI) in patients after multimodality treatment. METHODS: Between 1990 and
      2012, 800 BDI patients were referred to our tertiary center. Patient
      characteristics and long-term outcomes were described. RESULTS: PHx was performed
      in 11 patients (1.4%), mean age 48.3 years (range 29.3-83.5 years), mainly
      because of complex injury [Amsterdam classification type D (n = 10, 91%),
      Strasberg type E (n = 7, 64%) and Bismuth type IV (n = 8, 73%)]. In 7 patients
      (64%), concomitant vasculobiliary injury had occurred in the right hepatic artery
      (n = 3), proper hepatic artery (n = 1), portal vein (PV; n = 2) and the right
      hepatic artery and PV simultaneously (n = 1). Early PHx was performed in 2
      patients and delayed resection in 9 patients after a median of 57.8 months (range
      3.9-183.4 months). The in-hospital mortality was 18% (n = 2) and long-term
      mortality 9% (n = 1). There were no significant differences in postoperative
      complications between early and late resection. CONCLUSIONS: Indications for PHx
      after BDI in patients referred to a tertiary center are relatively low (1.4%) and
      generally apply to vasculobiliary injury. The implications for treatment are
      important, so it is worthwhile to classify vascular injuries in the management of
      BDI.

PMID- 24296789
TI  - Morphology and composition controlled Ga(x)In(1-x)Sb nanowires: understanding
      ternary antimonide growth.
AB  - Antimonide-based nanowires represent an important new class of material with
      great promise for both fundamental physics studies and various device
      applications. We report a comprehensive study on understanding the growth
      behaviour of GaxIn1-xSb nanowires on GaAs substrates using Au nanoparticles.
      First, the effect of growth parameters on the morphology and composition of
      GaxIn1-xSb nanowires is extensively studied over the entire compositional range
      (from 3 to ~100% of In). Second, the obtained compositional results are explained
      by a kinetic model, suggesting an Arrhenius-type behavior for the trimethylindium
      (TMIn) precursor. Third, the particle composition is fully investigated and the
      implications for growth are discussed with reference to our calculated Au-Ga-In
      phase diagram. Fourth, a mechanism is presented to explain the temperature
      dependent morphology and radial growth of the GaxIn1-xSb nanowires. Finally, we
      demonstrate homogeneous compositions in both axial and radial directions and the
      nanowires remain entirely twin-free zinc blende. The understanding gained from
      this study together with the potential to precisely tailor the band gap,
      wavelength and carrier mobilities allows fabrication of various GaxIn1-xSb-based
      nanowire devices.

PMID- 24296790
TI  - Photophysical behavior of a new cholesterol attached coumarin derivative and
      fluorescence spectroscopic studies on its interaction with bile salt systems and
      lipid bilayer membranes.
AB  - A new fluorescent-cholesterol (Cum-Chl) molecule has been synthesized by
      attaching 3-acetyl-7-(diethylamino)-2H-chromen-2-one (Cum) to cholesterol via
      cholesterol bound beta-keto ester. The beta-keto ester was synthesized from the
      corresponding nitrile by applying the Blaise reaction. The molecule forms H
      aggregates in solutions. The efficiency of aggregation is high in water. The H
      aggregates are non-fluorescent in non-aqueous solvents but fluorescent in water.
      Aqueous bile salt media suppress the formation of H-aggregates, this effect being
      more pronounced for sodium deoxycholate (NaDC) which is more hydrophobic. With
      increasing bile salt concentration, the enhancement of monomeric fluorescence
      intensity of Cum-Chl generally follows the progressive miceller aggregation of
      bile salts. Incorporation of Cum-Chl into the dimyristoylphosphatidylcholine
      (DMPC) lipid bilayer membrane results in a significant enhancement of monomeric
      fluorescence intensity. The variation of fluorescence intensity is also sensitive
      to the thermotropic phase transition of the bilayer. It is seen that in such
      aqueous micro- and nanoscale organized media like bile salts and lipid bilayer
      membranes the monomer-to-aggregate fluorescence intensity ratio reflects the
      state of organization of the medium. 

PMID- 24296791
TI  - Percutaneous coronary intervention outcomes in patients with stable obstructive
      coronary artery disease and myocardial ischemia: a collaborative meta-analysis of
      contemporary randomized clinical trials.
AB  - IMPORTANCE: Myocardial ischemia in patients with stable coronary artery disease
      (CAD) has been repeatedly associated with impaired survival. However, it is
      unclear if revascularization with percutaneous coronary intervention (PCI) to
      relieve ischemia improves outcomes compared with medical therapy (MT). OBJECTIVE:
      The objective of this study was to compare the effect of PCI and MT with MT alone
      exclusively in patients with stable CAD and objectively documented myocardial
      ischemia on clinical outcomes. DATA SOURCES: MEDLINE, Cochrane, and PubMed
      databases from 1970 to November 2012. Unpublished data were obtained from
      investigators. STUDY SELECTION: Randomized clinical trials of PCI and MT vs MT
      alone for stable coronary artery disease in which stents and statins were used in
      more than 50% of patients. DATA EXTRACTION: For studies in which myocardial
      ischemia diagnosed by stress testing or fractional flow reserve was required for
      enrollment, descriptive and quantitative data were extracted from the published
      report. For studies in which myocardial ischemia was not a requirement for
      enrollment, authors provided data for only those patients with ischemia
      determined by stress testing prior to randomization. The outcomes analyzed
      included death from any cause, nonfatal myocardial infarction (MI), unplanned
      revascularization, and angina. Summary odds ratios (ORs) were obtained using a
      random-effects model. Heterogeneity was assessed using the Q statistic and I2.
      RESULTS: In 5 trials enrolling 5286 patients, myocardial ischemia was diagnosed
      in 4064 patients by exercise stress testing, nuclear or echocardiographic stress
      imaging, or fractional flow reserve. Follow-up ranged from 231 days to 5 years
      (median, 5 years). The respective event rates for PCI with MT vs MT alone for
      death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and
      7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and
      28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91
      [95% CI, 0.57-1.44]). CONCLUSIONS AND RELEVANCE: In patients with stable CAD and
      objectively documented myocardial ischemia, PCI with MT was not associated with a
      reduction in death, nonfatal MI, unplanned revascularization, or angina compared
      with MT alone.

PMID- 24296792
TI  - Successful treatment of a young patient with locally advanced clear cell
      adenocarcinoma of the uterine cervix undergoing chemoradiation followed by
      radical surgery.
AB  - Clear cell adenocarcinoma (CCAC) of the uterine cervix is a rare variant of
      cervical adenocarcinoma accounting for approximately 4-9% of this disease. Given
      the rarity of this pathological entity, the optimal treatment management is far
      from being defined. Earlier evidence suggested that the prognosis of patients
      bearing cervical CCAC is worse than with other histotypes, thus making the
      investigation of multimodal treatment strategies clinically worthwhile. Herein,
      we report the first case of locally advanced, large size cervical CCAC in a young
      woman who was triaged to concomitant chemoradiotherapy followed by radical
      surgery and experienced a pathologically assessed optimal response to this
      multimodal approach.

PMID- 24296793
TI  - The phosphorylation of STAT6 during ischemic reperfusion in rat cerebral cortex.
AB  - For many years, brain ischemia has been known to be a leading cause of adult
      neurological disorder. In particular, many reports have shown that
      hyperexcitability of neurons and inflammatory response of the glia induced by
      ischemic reperfusion (I/R) determine the fate of cells in the ischemic core and
      the penumbra region. Although there are many reports on the activation and roles
      of signal transducer and activator of transcription (STAT) proteins (STAT1,
      STAT3, and STAT5) during hyperexcitation in the neuron and inflammation occurring
      following I/R, the temporal and spatial activation of STAT6 protein in the
      ischemic cortex still remain elusive. In this study, using a transient rat middle
      cerebral artery occlusion model, we primarily investigated the time-course
      expression of the phosphorylated STAT6 (pSTAT6) in the ischemic core region
      following I/R, which was compared with that of pSTAT3. We found that pSTAT6
      significantly decreases at 1 and 12 h following I/R, whereas pSTAT3 markedly
      increases at each follow-up time point. In addition, the level of pSTAT6 is
      reduced in the ischemic core in comparison with the penumbra region at 12 h
      following I/R. However, there is no significant difference in pSTAT3 expression
      between the ischemic core and the penumbra. Taken together, our data suggest that
      pSTAT6 and pSTAT3 are modulated differently following I/R during ischemic stroke.

PMID- 24296796
TI  - Definitions and outcomes of nutritional interventions in children with
      respiratory infections: the approach of the COMMENT initiative.
AB  - BACKGROUND/AIMS: This study is aimed at assessing definitions and outcomes used
      to measure the effects of nutrition in the prevention and treatment of
      respiratory tract infections in childhood. METHODS: We reviewed clinical trials
      studying the impact of nutritional interventions on upper and lower respiratory
      tract infections (URTI and LRTI), focusing on definitions and key outcomes.
      RESULTS: Fifty trials were included (46 on prevention and 4 on treatment). The
      definitions of respiratory infections were highly heterogeneous. In 15 of the
      trials, URTI or LRTI were diagnosed by a pediatrician. In 30 trials, definitions
      were based on symptoms reported by family members or field-workers only. Five
      trials did not provide any specific definition. Incidence was the most common
      outcome measure reported in the trials on prevention, and duration and illness
      severity were the most common in the treatment trials. CONCLUSIONS: The results
      showed a major heterogeneity with the use of a wide array of different
      definitions and clinical end points. To overcome these limitations, outcome
      measures might be differentiated into two categories: 'direct outcomes' in which
      respiratory infections are diagnosed and monitored by physicians according to
      rigorous definitions and 'indirect outcomes' (e.g. chest X-ray, antibiotic
      prescription and hospitalizations) to assess the burden of respiratory illnesses.
      Agreement on standard definitions and end points is needed to drive future
      trials.

PMID- 24296797
TI  - Propranolol inhibits growth of hemangioma-initiating cells but does not induce
      apoptosis.
AB  - BACKGROUND: Infantile hemangioma (IH) is the most common tumor of infancy. The
      first-line therapy for IH is propranolol, a nonselective beta-adrenergic receptor
      antagonist. However, mechanisms for the therapeutic effect of propranolol and
      regrowth of IH following cessation of treatment in some cases are not clear. We
      have recently shown that IH arises from multipotent stem cells. Whether IH stem
      cells are responsive to propranolol and are selectively targeted is unknown, and
      this is the focus of this study. METHODS: IH stem cells were exposed to
      propranolol and were assayed for cellular and molecular alterations. We used
      endothelial cells (ECs) as controls and bone marrow-derived mesenchymal
      progenitor cells (bm-MPCs) as normal stem/progenitor counterparts to determine
      selectivity. RESULTS: Our results show that propranolol significantly reduced IH
      stem cell growth but failed to induce caspase-3 activation. Normal bm-MPCs and
      mature ECs showed maintained or increased caspase-3 activation and significantly
      reduced cyclin-D1 levels. We further show that IH stem cells may escape apoptosis
      by inducing antiapoptotic pathways. CONCLUSION: This study reveals that
      propranolol does not induce apoptosis in IH stem cells, which is in contrast with
      the result for ECs. Escape from apoptosis in IH stem cells may involve induction
      of antiapoptotic pathways.

PMID- 24296798
TI  - Does visceral adiposity index signify early metabolic risk in children and
      adolescents?: association with insulin resistance, adipokines, and subclinical
      inflammation.
AB  - BACKGROUND: Visceral adiposity index (VAI) is a novel gender-specific index based
      on waist circumference (WC), BMI, and lipid parameters. Although VAI does not
      actually estimate visceral adiposity, it accurately reflects visceral fat
      function and insulin resistance. This index has not been studied in children thus
      far. This study aims to fill this gap. METHODS: In a cohort of Saudi children and
      adolescents, anthropometric measurements and metabolic/hormonal profile were
      obtained. RESULTS: A total of 543 subjects, 292 of whom were boys, were included
      (mean age: 11.9 +/- 3.3 y; BMI: 19.8 +/- 5.6 kg/m(2)). In all subjects, VAI was
      inferior to BMI and WC regarding its correlations with adiponectin, leptin,
      insulin resistance (homeostasis model of assessment-insulin resistance (HOMA
      IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it
      exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In
      stepwise multivariate analyses, only BMI was consistent as an independent
      predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index
      independently associated with glucose. CONCLUSION: Although VAI is related to
      glucose in children, it seems to be inferior to BMI in terms of association with
      insulin resistance, adipokines, and subclinical inflammation. Until specific
      studies can be performed in children, VAI should be extrapolated with caution in
      this age range.

PMID- 24296799
TI  - Relationship between acute kidney injury and brain MRI findings in asphyxiated
      newborns after therapeutic hypothermia.
AB  - BACKGROUND: We hypothesized that acute kidney injury (AKI) in asphyxiated
      neonates treated with therapeutic hypothermia would be associated with hypoxic
      ischemic lesions on brain magnetic resonance imaging (MRI). METHODS: Medical
      records of 88 cooled neonates who had had brain MRI were reviewed. All neonates
      had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h
      through cooling; and then on day 5 or 7 of life. A neonatal modification of the
      Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI.
      MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of
      interest was abnormal brain MRI at 7-10 d of life. RESULTS: AKI was found in 34
      (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and
      3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present
      in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI
      group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) =
      3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified
      AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary
      outcome. CONCLUSION: AKI is independently associated with the presence of hypoxic
      ischemic lesions on postcooling brain MRI.

PMID- 24296800
TI  - Fluorescence imaging lysosomal changes during cell division and apoptosis
      observed using Nile Blue based near-infrared emission.
AB  - , a Nile Blue based NIR fluorescent dye was reported. is highly effective in
      specifically labeling lysosomes with low concentration and good photostability in
      various kinds of live cells. It was first successfully used to observe the
      disappearance and reproduction of lysosomes during cell division. 

PMID- 24296801
TI  - Corneal involvement in uneventful cataract surgery: an in vivo confocal
      microscopy study.
AB  - PURPOSE: To evaluate corneal subbasal layer changes after uneventful cataract
      surgery by means of in vivo confocal microscopy. METHODS: This prospective study
      included 30 patients. Before surgery, and 1, 3, 6, 8 and 10 months after cataract
      surgery, all patients underwent a complete ophthalmological and confocal
      microscopy examination in the central and temporal corneal areas. Number of
      fibers, beading, tortuosity and reflectivity were analyzed. RESULTS: Important
      changes were shown in the central cornea up to 3 months after surgery: a
      reduction in nerve fiber number (baseline: 4.4 +/- 1.7; month 1: 1.2 +/- 0.5, p <
      0.0001; month 3: 2.5 +/- 1.2, p < 0.005) and reflectivity (baseline: 3.6 +/- 0.5;
      month 1: 1.4 +/- 0.6, p < 0.0001; month 3: 1.9 +/- 0.9, p < 0. 0001), and an
      increase in beading (baseline: 0.3 +/- 0.5 beads/100 um(2); month 1: 2.7 +/- 0.6
      beads/100 um(2), p < 0.0001; month 3: 2.6 +/- 0.5 beads/100 um(2), p < 0. 0001).
      The confocal parameters completely progressively recovered thereafter (60% at 6
      months, 87% at 8 and 10 months). The temporal plexus was absent at 1 month and
      fully recovered in all patients at month 8. CONCLUSION: Uneventful cataract
      surgery induces relevant corneal modifications when inspected by means of
      confocal microscopy.

PMID- 24296802
TI  - Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing
      renal inflammation, interstitial cell proliferation and oxidative stress.
AB  - BACKGROUND/AIMS: Prolonged elevation of serum aldosterone leads to renal
      fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We
      used a rat model of interstitial renal fibrosis to test the hypothesis that
      eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti
      inflammatory and anti-proliferative effects. METHODS: Eplerenone (a selective
      aldosterone blocker) or vehicle (control), was given to male Wistar rats (50
      mg/kg, twice daily) for 7 days before unilateral ureteral obstruction (UUO) and
      for an additional 28 days after surgery. Body weight, blood pressure, renal histo
      morphology, immune-staining for macrophages, monocyte chemotactic protein-1,
      proliferating cell nuclear antigen, alpha-smooth muscle actin, and serum and
      urine markers of renal function and oxidative stress were determined for both
      groups on 7, 14, and 28 days after surgery. RESULTS: Epleronone had no effect on
      body weight or blood pressure. However, eplerenone inhibited the development of
      renal fibrosis, inflammation (macrophage and monocyte infiltration), interstitial
      cell proliferation, and activation of interstitial cells (alpha-SMA expression).
      Epleronone also reduced oxidative stress. CONCLUSION: The anti-fibrotic effect of
      eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone
      inhibits renal inflammation, interstitial cell proliferation, phenotypic changes
      of interstitial cells, and reduces oxidative stress.

PMID- 24296803
TI  - The timing of reconstruction in severe mechanical trauma.
AB  - Serious ocular trauma involving the posterior segment remains rather common and,
      despite many technological advances in recent years, continues to represent a
      significant management challenge to the ophthalmologist. One of these challenges
      is to identify the most optimal timing for the ultimate reconstruction, namely
      vitrectomy. While it is fairly obvious that suture-closure of the wound of open
      globe injuries should be done as soon as possible, it is less clear whether
      vitrectomy should be performed in the same surgical session (primary
      comprehensive reconstruction) or be deferred (staged approach), and if so for how
      long. In this review, 4 options for staging are offered: early (days 2-4);
      delayed (days 5-7); late (days 8-14), and very late (past 2 weeks). The earlier
      the vitrectomy, the higher the risk of intraoperative complications. Conversely,
      the later the vitrectomy, the higher the incidence and severity of postoperative
      complications, of which proliferative vitreoretinopathy is the most damaging.

PMID- 24296804
TI  - Anticonvulsant medication use for the management of pain following spinal cord
      injury: systematic review and effectiveness analysis.
AB  - STUDY DESIGN: Systematic review and effectiveness analysis. OBJECTIVES: Assess
      the effectiveness of anticonvulsants for the management of post spinal cord
      injury (SCI) neuropathic pain. SETTING: Studies from multiple countries were
      included. METHODS: CINAHL, Cochrane, EMBASE and MEDLINE were searched up to April
      2013. Quality assessment was conducted using the Jadad and the Downs and Black
      tools. Effect sizes and odds ratios were calculated for primary and secondary
      outcome in the included studies. RESULTS: Gabapentinoids, valproate, lamotrigine,
      levetiracetam and carbamazepine were examined in the 13 included studies, ten of
      which are randomized controlled trials. Large effect size (0.873-3.362) for
      improvement of pain relief was found in 4 of the 6 studies examining the
      effectiveness of gabapentin. Pregabalin was shown to have a moderate to large
      effect (0.695-3.805) on improving neuropathic pain post SCI in 3 studies.
      Valproate and levetiracetam were not effective in improving neuropathic pain post
      SCI, while lamotrigine was effective in reducing neuropathic pain amongst persons
      with incomplete lesions and carbamazepine was found effective for relief of
      moderate to intense pain. CONCLUSION: Gabapentin and pregabalin are the two
      anticonvulsants which have been shown to have some benefit in reducing
      neuropathic pain.

PMID- 24296806
TI  - Comparison of gait between healthy participants and persons with spinal cord
      injury when using a powered gait orthosis-a pilot study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a powered gait
      orthosis (PGO) on the temporal-spatial parameters and kinematics of walking in
      both healthy participants and persons with spinal cord injury (SCI) using three
      dimensional motion analysis to facilitate further development of such devices.
      METHODS: Kinematics and temporal spatial data were obtained from three healthy
      participants and four persons with SCI who walked using the same design of PGO.
      RESULTS: Walking speed was reduced by 28% and step length by 29% in healthy
      individuals when walking with PGO compared with normal walking and that recorded
      for persons with SCI was approximately one-third that of normal walking. There
      were significant differences in hip and knee joint ranges of motion in comparison
      between walking with PGO in healthy participants and walking with PGO in persons
      with SCI. CONCLUSION: Walking with a PGO by healthy participants significantly
      reduced critical gait parameters, and further development work is needed to
      produce a more effective device to match closely the gait parameters of normal
      walking by healthy participants. Significant differences between normal walking
      and that evidenced with the PGO by both healthy participants and persons with SCI
      were detected.

PMID- 24296805
TI  - Race-ethnicity and poverty after spinal cord injury.
AB  - STUDY DESIGN: Secondary analysis of existing data. OBJECTIVE: Our objective was
      to examine the relationship between race-ethnicity and poverty status after
      spinal cord injury (SCI). SETTING: A large specialty hospital in the southeastern
      United States. METHODS: Participants were 2043 adults with traumatic SCI in the
      US. Poverty status was measured using criteria from the US Census Bureau.
      RESULTS: Whereas only 14% of non-Hispanic White participants were below the
      poverty level, 41.3% of non-Hispanic Blacks were in poverty. Logistic regression
      with three different models identified several significant predictors of poverty,
      including marital status, years of education, level of education, age and
      employment status. Non-Hispanic Blacks had 2.75 greater odds of living in poverty
      after controlling for other factors, including education and employment.
      CONCLUSION: We may need to consider quality of education and employment to better
      understand the elevated risk of poverty among non-Hispanic Blacks in the US.

PMID- 24296807
TI  - Expression of cytokines, growth factors and apoptosis-related signal molecules in
      chronic pressure ulcer wounds healing.
AB  - OBJECTIVES: Many complex mechanisms responsible for the pathogenesis of pressure
      ulcers (PUs) currently remain poorly understood. The objective of this study was
      to discover the major roles for inflammatory cytokines, growth factors and
      several apoptosis-related signal molecules in chronic PU wound. METHODS: We
      investigated expression of inflammatory cytokines, growth factors and their
      corresponding receptors, and the apoptosis signal of caspase-3 in chronic stage
      III/IV chronic PU wound, acute wounds as well as normal skin controls. Tissues
      were stained by hematoxylin and eosin (HE) for histopathology and Masson's
      trichrome for collagen. Vascular endothelial growth factor (VEGF), fibroblast
      growth factors 2 (bFGF) and caspase-3 were detected by immunohistochemical
      analysis. Expression of mRNAs for interleukin (IL)-1beta, tumor necrosis factor
      alpha (TNF-alpha), VEGF, KDR, bFGF and FGFR1 was determined by real-time reverse
      transcription PCR. RESULTS: Stage III and IV chronic PUs stained had increased
      inflammatory cell infiltration and decreased collagen compared with controls.
      Levels of mRNAs for inflammatory cytokines IL-1beta and TNF-alpha were elevated
      in PUs compared with acute wounds and normal skin. VEGF and bFGF, together with
      their receptors KDR and FGFR1, respectively, were significantly decreased
      compared with controls. However, the expression levels of caspase-3 were elevated
      in the PUs. CONCLUSION: Our series of studies have shown that chronic PUs
      displayed high levels of inflammation and disruption of the collagen matrix,
      along with increased indications of apoptosis and decreased levels of growth
      factors and their receptors. These characteristics can be used to comprehensively
      evaluate the etiology and treatment of chronic PUs.

PMID- 24296808
TI  - Prevalence and associated factors of T-score discordance between different sites
      in Iranian patients with spinal cord injury.
AB  - OBJECTIVES: The present study was conducted to determine the prevalence of T
      score discordance and its risk factors in a group of patients with spinal cord
      injury in a university teaching hospital in the Iranian capital of Tehran.
      METHODS: This cross-sectional study was conducted on paraplegic men undergoing
      bone density testing in an outpatient clinic at a hospital in the Iranian
      capital, Tehran, between March 2011 and 2012. A questionnaire on demographic and
      anthropometric characteristics, including age, height, weight, engagement in
      physical activity and personal smoking habits, was filled out for each subject.
      All the subjects underwent bone mineral density measurement and blood samples
      were sent for laboratory testing. RESULTS: Major T-score discordance between two
      sites was noted in 54 (41.22%) patients. Multivariate logistic regression
      revealed that every unit increase in serum calcium levels, as the only factor
      influencing T-score discordance, was associated with a 2.49-fold increased risk
      in T-score discordance in the area. As for the spine and radius, BMI was the only
      influencing factor as every unit increase in BMI was associated with a 14% lower
      risk for T-score discordance in these regions. Body mass index was the only
      factor, based on the multivariate model, affecting the risk of developing T-score
      discordance between two sites. CONCLUSION: Our study revealed the high prevalence
      of T-score discordance in patients with spinal cord injury. Physicians should
      therefore be encouraged to perform BMD at three sites when visiting patients with
      such injuries.

PMID- 24296809
TI  - OK-432 synergizes with IFN-gamma to confer dendritic cells with enhanced
      antitumor immunity.
AB  - Generation of functional dendritic cells (DCs) with boosted immunity after the
      withdrawal of initial activation/maturation conditions remains a significant
      challenge. In this study, we investigated the impact of a newly developed
      maturation cocktail consisting of OK-432 and interferon-gamma (IFN-gamma) on the
      function of human monocyte-derived DCs (MoDCs). We found that OK-432 plus IFN
      gamma stimulation could induce significantly stronger expression of surface
      molecules, production of cytokines, as well as migration of DCs compared with OK
      432 stimulation alone. Most importantly, DCs matured with OK-432 plus IFN-gamma
      induced maintained secretion of interleukin-12 (IL-12)p70 in secondary culture
      after stimulus withdrawal. Functionally, OK-432 plus IFN-gamma-conditioned DCs
      induce remarkable Th1 and Tc1 responses more effectively than OK-432 alone, even
      more than the use of alpha-type-1 cytokine cocktail. As a result, DCs matured
      with OK-432 plus IFN-gamma can prime stronger cytotoxic lymphocyte (CTL) and
      natural killer (NK) cell response against tumor cells in vitro. Peripheral blood
      mononuclear cells activated by DCs matured with OK-432 plus IFN-gamma also showed
      greater tumor growth inhibition in vivo in null mice. Molecular mechanistic
      analysis showed that DC maturation using IFN-gamma in concert with OK-432
      involves the activation of p38 and nuclear factor-kappa B (NF-kappaB) pathways.
      This study provided a novel strategy to generate more potent immune segments in
      DC vaccine.

PMID- 24296810
TI  - Associations between surface markers on blood monocytes and carotid
      atherosclerosis in HIV-positive individuals.
AB  - Chronic HIV infection is associated with increased risk of cardiovascular disease
      (CVD), including in patients with virological suppression. Persistent innate
      immune activation may contribute to the development of CVD via activation of
      monocytes in these patients. We investigated whether changes in monocyte
      phenotype predict subclinical atherosclerosis in virologically suppressed HIV
      positive individuals with low cardiovascular risk. We enroled 51 virologically
      suppressed HIV-positive individuals not receiving protease inhibitors or statins
      and 49 age-matched uninfected controls in this study. Carotid artery intima-media
      thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk
      factors, including Framingham risk scores, were recorded. Markers of monocyte
      activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in
      whole-blood samples by flow cytometry. Associations were assessed using
      univariate and multivariate median regressions. Median cIMT was similar between
      HIV-positive and HIV-negative participants (P=0.3), although HIV-positive
      patients had significantly higher Framingham risk score (P=0.009) and systemic
      inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently
      predicted carotid artery thickness in HIV-positive individuals after controlling
      for Framingham risk score (P=0.025 and 0.015, respectively). These markers were
      not predictive of carotid artery thickening in controls. Our study indicates that
      monocyte surface markers may serve as novel predictors of CVD in HIV-positive
      individuals and is consistent with an important role for monocyte activation in
      the progression of HIV-related cardiovascular pathology. 

PMID- 24296812
TI  - Phenotypic and transcriptional profile correlates with functional plasticity of
      antigen-specific CD4+ T cells.
AB  - The role of CD4(+) T cells in the control of infectious pathogens is highly
      complex with a myriad of functions but how these T cells acquire differential
      functional potentiality remains poorly defined. Here we show that human
      cytomegalovirus (CMV)-specific CD4(+) T cells directed towards different viral
      antigens expressed predominantly TNF-alpha alone or TNF-alpha and IFN-gamma. TNF
      alpha(+) and IFN-gamma(+) CD4(+) T cells expressed significantly higher levels of
      T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes)
      expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-alpha(+) CD4(+) T cells
      expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)). Furthermore,
      TNF-alpha(+) and IFN-gamma(+) CD4(+) T cells expressed significantly higher
      levels of perforin and interleukin (IL)-2 and displayed a terminally
      differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)). In contrast,
      TNF-alpha(+) alone CMV-specific CD4(+) T cells were predominantly early-memory
      phenotype with a proportion of these cells displaying T memory stem-cell
      phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)). In vitro stimulation of CMV-specific
      CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to
      dramatically change the transcriptional and functional profile of TNF-alpha(+)
      CD4(+) T cells, whereas TNF-alpha(+) and IFN-gamma(+) CD4(+) T cells remained
      unaltered. These findings illustrate an intrinsic link between cytokine
      expression, transcriptional regulation and cellular differentiation, and their
      impact on functional plasticity of virus-specific CD4(+) T cells. 

PMID- 24296811
TI  - Mechanisms of IL-8 suppression by Treponema denticola in gingival epithelial
      cells.
AB  - The purpose of this study was to investigate the mechanism(s) of interleukin (IL)
      8 suppression by Treponema denticola, one of the major periodontal pathogens, in
      gingival epithelial cells. Immortalized human gingival epithelial HOK-16B cells
      were infected with wild-type (WT), dentilisin-deficient (K1) or flagellin
      deficient (flgE) T. denticola in the presence or absence of 2% human serum for 24
      h. The levels of IL-8 expression were measured with real-time reverse
      transcription PCR and ELISA. In the absence of human serum, the WT and flgE, but
      not K1, substantially reduced not only the levels of IL-8 protein but also of IL
      8 mRNA. Such downregulation of IL-8 mRNA was independent of bacterial invasion.
      Degradation of cytokine mixture by the WT, K1 and flgE revealed dentilisin
      dependent preferential degradation of tumor necrosis factor (TNF)-alpha, an IL-8
      inducing cytokine. WT and flgE significantly decreased the levels of TNFalpha
      secreted by HOK-16B cells, suggesting modulation of IL-8 through dentilisin
      mediated degradation of TNFalpha. The addition of human serum to the culture
      potentiated the suppressive effect of T. denticola, resulting in substantial
      reductions of IL-8 and TNFalpha levels, even by K1. The serum-dependent effects
      of T. denticola were attributed to its ability to suppress the accumulation of
      intracellular reactive-oxygen species (ROS), a group of ubiquitous signaling
      molecules. Pretreatment with an antioxidant suppressed TNFalpha-induced IL-8
      expression, confirming the role of ROS in TNFalpha signaling. Collectively, T.
      denticola targeted a key inflammatory cytokine and its signaling molecule to
      modulate the host innate immune response, which provides a new insight into
      modulation of host immunity by a periodontal pathogen.

PMID- 24296813
TI  - Inflammatory and neurodegeneration markers during asymptomatic HSV-1
      reactivation.
AB  - BACKGROUND: Currently, it is unclear whether asymptomatic recurrent reactivations
      of herpes simplex virus type 1 (HSV-1) occur in the central nervous systems of
      infected people, and if these events could lead to a progressive deterioration of
      neuronal function. In this context, HSV-1 constitutes an important candidate to
      be included among the risk factors for the development of neuropathies associated
      with chronic neuroinflammation. OBJECTIVE: The aim of this study was to assess in
      vivo inflammatory and neurodegenerative markers in the brain during productive
      and latent HSV-1 infection using a mouse model of herpes simplex encephalitis.
      METHODS: Neuroinflammation and neurodegeneration markers were evaluated in mice
      trigeminal ganglia and cerebral cortex during HSV-1 infection, by
      immunohistochemistry, western blot, and RT-PCR. RESULTS: Neuronal ICP4 viral
      antigen expression indicative of a reactivation episode during asymptomatic
      latency of HSV-1 infection in mice was accompanied by upregulation of
      neuroinflammatory (toll-like receptor-4, interferon alpha/beta, and p-IRF3) and
      early neurodegenerative markers (phospho-tau and TauC3). CONCLUSIONS: HSV-1
      reactivation from latency induced neuroinflammatory and neurodegenerative markers
      in the brain of asymptomatic mice suggesting that recurrent reactivations could
      be associated with cumulative neuronal dysfunctions.

PMID- 24296814
TI  - Treatment of primary progressive aphasias by transcranial direct current
      stimulation combined with language training.
AB  - BACKGROUND: Primary progressive aphasia (PPA) is an untreatable neurodegenerative
      disorder that disrupts language functions. Previous studies have demonstrated
      transcranial direct current stimulation (tDCS) may improve language symptoms in
      patients with post stroke aphasia or neurodegenerative diseases. OBJECTIVE: The
      present study investigated whether the application of anodal tDCS (AtDCS) to the
      scalp overlying the left dorsolateral prefrontal cortex (DLPFC), which may
      increase cortical excitability, in combination with individualized speech therapy
      would improve naming accuracy in the agrammatic variant of PPA (avPPA). METHODS:
      Sixteen avPPA patients were randomly allocated into two subgroups: AtDCS (n = 8)
      or placebo tDCS (PtDCS). tDCS was applied over the left DLPFC (BA 8/9) 25 minutes
      per day for two weeks (10 days). Each patient underwent 25 minutes of
      individualized speech therapy with either AtDCS or PtDCS during each treatment
      session. Neuropsychological assessment, experimental naming, and linguistic
      abilities in daily living were assessed at baseline (T0), after two weeks of
      intervention (T1) and at a 12-week follow-up (T2). RESULTS: Significant
      improvement in experimental naming was observed in both groups at T1 and T2, but
      this effect was significantly greater in AtDCS than PtDCS patients. Naming
      correctness, as assessed using the Aachener Aphasie Test, increased selectively
      in the AtDCS group from T0 to T1, and this effect remained significant at T2. The
      analysis of daily living language abilities improved selectively in AtDCS group.
      CONCLUSION: Our results support the beneficial effect of targeted language
      training in combination with brain stimulation in avPPA patients. tDCS should be
      considered a useful tool for the improvement of language functions in patients
      with neurodegenerative diseases in future trials.

PMID- 24296815
TI  - Physical activity reduces the risk of dementia in mild cognitive impairment
      subjects: a cohort study.
AB  - BACKGROUND: Leisure activities, particularly exercise, play a protective role
      against dementia in healthy people, but it is unknown if this protective effect
      could be generalized to subjects with mild cognitive impairment (MCI). OBJECTIVE:
      To investigate the influence of leisure activities on the risk of progression of
      MCI to dementia. METHODS: 176 MCI subjects attending a memory clinic underwent a
      standardized lifestyle questionnaire between October 2007 and May 2010. Social,
      cognitive, and physical scores were derived based on the assiduity of
      interpersonal contacts and on the frequency of participation in individual
      leisure activities. Subjects were requested to return every 12 months for
      dementia surveillance. The outcome measure was the risk of dementia associated
      with social, cognitive, and physical scores. RESULTS: Over a median follow-up
      time of 2.59 year, 92 (52.2%) MCI subjects developed dementia. Subjects with
      physical scores in the highest third had a lower risk (HR 0.44; 95% CI 0.23-0.85)
      of dementia compared with those in the lowest third. No association was found
      between cognitive or social scores and the risk of dementia. CONCLUSION: To our
      knowledge, this is the first prospective clinical study which demonstrates that
      high levels of participation in physical leisure activities are associated with
      reduced risk of dementia in subjects with MCI. In line with findings coming from
      community-based studies on healthy elderly, our finding suggests that the
      protective role of exercise against the development of dementia can be
      generalized to MCI subjects seen in clinical practice. Clinicians should
      encourage MCI subjects to participate in physical leisure activities.

PMID- 24296816
TI  - Pharmacologic therapy for female sexual dysfunction.
AB  - Female sexual dysfunction (FSD) is a common health issue that can have
      significant negative effects on overall well-being and quality of life. The
      primary purpose of this article is to review commonly noted pharmacologic
      therapies for FSD. The pathophysiology, clinical evaluation, and selected
      nonpharmacologic therapies are also briefly addressed as well as recommendations
      for practice.

PMID- 24296817
TI  - Comparing performance of different laryngoscope blades.

PMID- 24296818
TI  - Endotracheal tube cuff inflation with and without a pressure gauge to minimise
      sevoflurane pollution during intermittent positive pressure ventilation.

PMID- 24296819
TI  - Safety and effectiveness of bilateral continuous sciatic nerve block for
      bilateral orthopaedic foot surgery: a cohort study.
AB  - BACKGROUND: Severe postoperative pain is a major problem after unilateral and
      bilateral foot surgery. Continuous regional anaesthesia is often used for
      unilateral surgery. However, for bilateral surgery, the incidence of
      complications of continuous bilateral compared with unilateral regional
      anaesthesia is unknown. OBJECTIVES: To assess the incidence of catheter-related
      complications of bilateral compared with unilateral continuous regional
      anaesthesia. DESIGN: A prospective observational study. SETTING: Bellinzona
      Regional Hospital, a tertiary teaching hospital. PATIENTS: Patients (n = 130)
      scheduled for elective bilateral or unilateral hallux valgus repair treated with
      continuous popliteal sciatic nerve block using a continuous infusion of
      ropivacaine 0.15% at 5 ml h for each popliteal catheter by elastomeric pumps.
      INTERVENTIONS: The incidence of catheter-related complications, effectiveness,
      pain levels at rest and with motion, patient satisfaction for the first three
      postoperative days and the incidence of ambulatory visits or readmissions after
      discharge were measured. A follow-up for neurological or other complications
      related to regional anaesthesia was performed 6 to 8 weeks after surgery. MAIN
      OUTCOME MEASURE: The incidence of catheter-related complications comparing
      bilateral with unilateral continuous sciatic popliteal nerve block. RESULTS:
      There were no differences in the incidence of catheter-related complications
      between the groups. Pain scores at rest and with motion were comparable between
      the groups. All patients were fit for discharge home 3 days after surgery.
      Patient satisfaction was similar between the groups. There were no unplanned
      ambulatory visits or readmissions due to complications in either group. No
      complications related to regional anaesthesia were reported during the follow-up.
      CONCLUSION: The complication rate, effectiveness and patient satisfaction of
      bilateral continuous popliteal sciatic nerve block was comparable with unilateral
      continuous sciatic popliteal nerve block. The follow-up showed that bilateral
      continuous sciatic popliteal nerve block does not increase the complication rate.
      However, an outpatient-based study should confirm these data prior to
      introduction in the ambulatory setting.

PMID- 24296820
TI  - Reply to: anaesthesiological support in a cardiac electrophysiology laboratory.

PMID- 24296821
TI  - ESA guidelines on the management of severe perioperative bleeding: comments on
      behalf of the Subcommittee on Transfusion and Haemostasis of the European
      Association of Cardiothoracic Anaesthesiologists.

PMID- 24296822
TI  - Reply to: ESA guidelines on the management of severe perioperative bleeding.

PMID- 24296823
TI  - Short-term outcomes of coaxial microincision cataract surgery for uveitis
      associated cataract without postoperative systemic steroid therapy.
AB  - PURPOSE: To study the necessity of prophylactic systemic steroid therapy after
      coaxial microincision cataract surgery (MICS) conducted in aged patients during
      remission of uveitis. PROCEDURES: A total of 17 consecutive patients who
      underwent MICS were enrolled in this retrospective study. The median age was 73
      years. MICS via a 2.2-mm incision was performed. None of the patients received
      systemic steroid administration after surgery. The visual acuity, intraocular
      pressure (IOP) and inflammation scores were recorded. RESULTS: The mean logMAR
      visual acuity was significantly improved from 0.56 +/- 0.58 to 0.10 +/- 0.30, and
      the mean inflammation score was reduced from 0.20 to 0.14. Postoperative
      complications were recurrence of ocular inflammation in 1 eye and elevation of
      IOP more than 21 mm Hg in 1 eye, which were resolved by topical steroids and
      topical antiglaucoma medication. CONCLUSIONS: Prophylactic systemic steroid
      therapy after MICS may not be necessary in aged uveitis patients without
      posterior complications before cataract surgery.

PMID- 24296824
TI  - A coarse-grained simulation to study the digestion and bioaccessibility of
      lipophilic nutrients and micronutrients in emulsion.
AB  - The digestion of lipophilic nutrients and micronutrients requires numerous and
      simultaneous processes of chemical, physical and biological nature. Studying
      these processes experimentally is challenging, explaining why there is only
      little information about the mechanisms and interactions involved. Nevertheless,
      the bioaccessibility of lipophilic micronutrients is poorly understood so new
      investigation approaches are needed, all the more when digestion of lipophilic
      nutrients is also involved. In this article, the development of a coarse-grained
      simulation with no adjustable parameter is reported, enabling the study of the
      chemical and physical processes controlling bioaccessibility in such systems. The
      intestinal digestion of a droplet of a pure triglyceride containing a lipophilic
      vitamin was simulated to obtain their bioaccessibility kinetics (via lipolysis
      and/or solubilization in bile salt). The parameters examined here were the type
      of triglyceride, the type of vitamin, the digestive fluid amount, the droplet
      size, and different digestion conditions reflecting the in vitro or in vivo
      cases. Among these structure and composition parameters, the type of triglyceride
      and the digestion conditions had the greatest effects on bioaccessibility. An
      interplay between triglyceride digestion and micronutrient bioaccessibility
      kinetics was evidenced, highlighting the roles of the different parameters, in
      agreement with the experimental literature. This new approach is shown to be
      relevant to both nutrition and pharmacology. 

PMID- 24296826
TI  - Follow-up imaging for vertebral osteomyelitis: a teachable moment.

PMID- 24296827
TI  - The state of RT-quantitative PCR: firsthand observations of implementation of
      minimum information for the publication of quantitative real-time PCR experiments
      (MIQE).
AB  - In the past decade, the techniques of quantitative PCR (qPCR) and reverse
      transcription (RT)-qPCR have become accessible to virtually all research labs,
      producing valuable data for peer-reviewed publications and supporting exciting
      research conclusions. However, the experimental design and validation processes
      applied to the associated projects are the result of historical biases adopted by
      individual labs that have evolved and changed since the inception of the
      techniques and associated technologies. This has resulted in wide variability in
      the quality, reproducibility and interpretability of published data as a direct
      result of how each lab has designed their RT-qPCR experiments. The 'minimum
      information for the publication of quantitative real-time PCR experiments' (MIQE)
      was published to provide the scientific community with a consistent workflow and
      key considerations to perform qPCR experiments. We use specific examples to
      highlight the serious negative ramifications for data quality when the MIQE
      guidelines are not applied and include a summary of good and poor practices for
      RT-qPCR.

PMID- 24296825
TI  - Time to hospital admission and start of treatment in patients with ischemic
      stroke in northern Italy and predictors of delay.
AB  - BACKGROUND AND PURPOSE: Early treatment (i.e. thrombolysis) is crucial for a
      successful care of ischemic stroke. In the management of stroke, two phases are
      crucial: the pre-hospital and the in-hospital interval. This work investigated
      factors influencing pre- and in-hospital delay in a large geographic area of
      Northern Italy. METHODS: Enrolled were patients presenting with ischemic stroke
      in four administrative districts of Northern Italy (Como, Lecco, Sondrio and
      Varese) over a 4-month period. Pre-hospital time and in-hospital time with single
      management steps were recorded prospectively. Age, gender, recruiting hospital,
      EMS transport and triage codes, clinical severity and thrombolytic treatment were
      also recorded. Univariate and multivariate analysis of factors predicting pre-
      and in-hospital delay were performed. RESULTS: Median pre-hospital time and in
      hospital time were, respectively, 120 min (interquartile range, IQR 62-271) and
      150 min (IQR 80-214). Pre-hospital time was halved in patients hospitalized via
      EMS (p<0.001) and clinically more severe (p<0.001). At multivariate analysis,
      transport code was associated with delay at any time (p<0.05). CONCLUSIONS: EMS
      use and transport code predicted treatment delay in patients with ischemic
      stroke. A more intensive use of EMS and high urgency codes could help increase
      the number of stroke patients treated appropriately.

PMID- 24296829
TI  - Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF
      ligand-neutralizing antibody, and mechanistic rationale for combination with
      rapamycin.
AB  - Insulin-like growth factor (IGF) signaling is thought to play a role in the
      development and progression of multiple cancer types. To date, therapeutic
      strategies aimed at disrupting IGF signaling have largely focused on antibodies
      that target the IGF-I receptor (IGF-IR). Here, we describe the pharmacologic
      profile of BI 836845, a fully human monoclonal antibody that utilizes an
      alternative approach to IGF signaling inhibition by selectively neutralizing the
      bioactivity of IGF ligands. Biochemical analyses of BI 836845 demonstrated high
      affinity to human IGF-I and IGF-II, resulting in effective inhibition of IGF
      induced activation of both IGF-IR and IR-A in vitro. Cross-reactivity to rodent
      IGFs has enabled rigorous assessment of the pharmacologic activity of BI 836845
      in preclinical models. Pharmacodynamic studies in rats showed potent reduction of
      serum IGF bioactivity in the absence of metabolic adverse effects, leading to
      growth inhibition as evidenced by reduced body weight gain and tail length.
      Moreover, BI 836845 reduced the proliferation of human cell lines derived from
      different cancer types and enhanced the antitumor efficacy of rapamycin by
      blocking a rapamycin-induced increase in upstream signaling in vitro as well as
      in human tumor xenograft models in nude mice. Our data suggest that BI 836845
      represents a potentially more effective and tolerable approach to the inhibition
      of IGF signaling compared with agents that target the IGF-I receptor directly,
      with potential for rational combinations with other targeted agents in clinical
      studies.

PMID- 24296830
TI  - Cytotoxicity of halogenated graphenes.
AB  - Graphene and its family of derivatives possess unique and remarkable
      physicochemical properties which make them valuable materials for applications in
      many areas like electronics, energy storage and biomedicine. In response to the
      possibility of its large-scale manufacturing as commercial products in the
      future, an investigation was conducted to determine the cytotoxicity of one
      particular family of graphene derivatives, the halogenated graphenes, for the
      first time. Halogenated graphenes were prepared through thermal exfoliation of
      graphite oxide in gaseous chlorine, bromine or iodine atmospheres to yield
      chlorine- (TRGO-Cl), bromine- (TRGO-Br) and iodine-doped graphene (TRGO-I)
      respectively. 24 h exposure of human lung carcinoma epithelial cells (A549) to
      the three halogenated graphenes and subsequent cell viability assessments using
      methylthiazolyldiphenyl-tetrazolium bromide (MTT) and water-soluble tetrazolium
      salt (WST-8) assays revealed that all the halogenated graphenes examined are
      rather cytotoxic at the concentrations tested (3.125 MUg mL(-1) to 200 MUg mL(
      1)) and the effects are dose-dependent, with TRGO-Cl reducing the cell viability
      to as low as 25.7% at the maximum concentration of 200 MUg mL(-1). Their levels
      of cytotoxicity can be arranged in the order of TRGO-Cl > TRGO-Br > TRGO-I, and
      it is suggested that the amount of halogen present in the graphene material is
      the determining factor for the observed trend. Control experiments were carried
      out to test for possible nanomaterial-induced interference as a consequence of
      reaction between the halogenated graphenes and the viability markers (MTT/WST-8
      reagent) or binding of the formazan products under cell-free conditions. The data
      obtained eliminate the probability of significant influence by these interferents
      as the change in the normalized percentage of formazan formed is relatively small
      and thorough washings were performed prior to the viability assessments to reduce
      the amount of halogenated graphenes that could eventually interact with the
      MTT/WST-8 assays. More studies need to be carried out in the future to complement
      the results obtained in this initial study in an attempt to develop a better
      understanding of the health hazards that the halogenated graphenes pose. 

PMID- 24296828
TI  - Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2
      gatekeeper mutation and NF1 loss.
AB  - The treatment of non-small cell lung cancer has evolved dramatically over the
      past decade with the adoption of widespread use of effective targeted therapies
      in patients with distinct molecular alterations. In lung squamous cell carcinoma
      (lung SqCC), recent studies have suggested that DDR2 mutations are a biomarker
      for therapeutic response to dasatinib and clinical trials are underway testing
      this hypothesis. Although targeted therapeutics are typically quite effective as
      initial therapy for patients with lung cancer, nearly all patients develop
      resistance with long-term exposure to targeted drugs. Here, we use DDR2-dependent
      lung cancer cell lines to model acquired resistance to dasatinib therapy. We
      perform targeted exome sequencing to identify two distinct mechanisms of acquired
      resistance: acquisition of the T654I gatekeeper mutation in DDR2 and loss of NF1.
      We show that NF1 loss activates a bypass pathway, which confers ERK dependency
      downstream of RAS activation. These results indicate that acquired resistance to
      dasatinib can occur via both second-site mutations in DDR2 and by activation of
      bypass pathways. These data may help to anticipate mechanisms of resistance that
      may be identified in upcoming clinical trials of anti-DDR2 therapy in lung cancer
      and suggest strategies to overcome resistance.

PMID- 24296831
TI  - Problems and perspectives of ophthalmic research in Germany: results from a
      national survey.
AB  - PURPOSE: To identify and describe the most relevant obstacles to carrying out
      ophthalmic research in Germany. METHODS: Two research methods were used to assess
      current problems in ophthalmic research. First, 55 expert interviews were
      conducted with major stakeholders in ophthalmic research, and key problems were
      identified. An online questionnaire was then sent to 3,080 German
      ophthalmologists, of whom 927 responded by evaluating the current research
      situation within ophthalmology in Germany. We devised a score to rank areas of
      concern by multiplying the responders' rate, ranging between -3 ('I disagree
      completely') and +3 ('I fully agree'), with the percentage of response
      frequencies. The maximum possible score was 300. RESULTS: The lack of
      opportunities to combine clinical work and research (score: 231.8) as well as
      unattractive career perspectives (175.7) were identified as the most relevant
      problems. Further barriers were difficulties in acquiring research funds (155.7),
      organizational problems at the local level (143.7) and a lack of support for
      women (24.1; among women: 122.3). Potential improvement was expected in
      particular from exemption from clinical work for scientific purposes; this was
      found to be more appealing than more prestigious awards for research
      achievements. A widely held position was that research projects should focus more
      closely on common eye diseases, and that vision research needs a more prominent
      profile among politicians and in the public arena. CONCLUSION: Our findings may
      help to initiate improvements in both research performance and outcomes.

PMID- 24296832
TI  - Regression of experimentally induced endometriosis with a new selective
      cyclooxygenase-2 enzyme inhibitor.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) levels increase in women with endometriosis.
      COX-2, via increasing prostaglandin E2, contributes to an increase in vascular
      endothelial growth factor. In this way, COX-2 may contribute to the progression
      and continuity of endometriosis. We investigated the effect of dexketoprofen
      trometamol, a new selective COX-2 enzyme inhibitor, on experimentally induced
      endometriotic cysts. METHODS: Experimental endometriotic cysts were created in 60
      adult female Wistar albino rats. The rats were randomized to 2 equal groups, a
      control (group Con) and a dexketoprofen (group Dex) group. Six weeks later, cyst
      volumes were measured as in vivo (volume 1). Following volume 1 measurement, for
      4 weeks group Con received 0.1 ml distilled water; group Dex received 0.375 mg
      dexketoprofen trometamol/0.1 ml distilled water, intramuscularly, twice a day. At
      the end of administration, the cyst volumes were remeasured (volume 2), and the
      cysts totally excised and weighed. Glandular (GT) and stromal tissues (ST) and
      natural killer (NK) cell contents in the cyst wall were scored. RESULTS: NK cell
      content and volume 1 were not different between the 2 groups. Volume 2, cyst
      weight, and GT and ST contents in group Dex were significantly lower than those
      in group Con. CONCLUSION: Dexketoprofen trometamol significantly reduced the
      development of experimentally induced endometriotic cysts both macroscopically
      and microscopically.

PMID- 24296833
TI  - A new generation of cysteine derivatives with three active antioxidant centers:
      improving reactivity and stability.
AB  - The development of new antioxidants with enhanced activity constitutes a very
      active research field as it can contribute to the improvement of human health.
      Although the antioxidant activity occurs through different mechanisms, usually
      most of the antioxidant molecules present a unique active center which is able to
      react following a specific way. To overcome this weakness and in the belief that
      the coupling of different antioxidant groups is a good strategy to obtain
      multipotent antioxidants, the effect of introducing different N-protective groups
      on the cysteine core is evaluated by using DFT. As a result, in this work we
      present a multicenter antioxidant, N-(9-fluorenylmethyloxycarbonyl)cysteine
      methyl ester 8, able to fight efficiently through different mechanisms against
      free radicals independently of their nature. This antioxidant appears to be the
      first one of a promising new class of multipotent antioxidants with three
      operative centers: C(alpha) that is a good hydrogen donor, the Fmoc group that is
      a good electron donor and the all-around thiol group. Besides, its neutral
      radical shows a high stability due to the captodative effect in such a way that
      the subsequent toxic effects would be avoided. Then, its experimental radical
      trapping antioxidant activity postulates compound 8 as a prototype of
      antioxidants more versatile and efficient than N-acetylcysteine, ascorbic acid or
      Trolox.

PMID- 24296834
TI  - Computational optimisation of targeted DNA sequencing for cancer detection.
AB  - Despite recent progress thanks to next-generation sequencing technologies,
      personalised cancer medicine is still hampered by intra-tumour heterogeneity and
      drug resistance. As most patients with advanced metastatic disease face poor
      survival, there is need to improve early diagnosis. Analysing circulating tumour
      DNA (ctDNA) might represent a non-invasive method to detect mutations in
      patients, facilitating early detection. In this article, we define reduced gene
      panels from publicly available datasets as a first step to assess and optimise
      the potential of targeted ctDNA scans for early tumour detection. Dividing 4,467
      samples into one discovery and two independent validation cohorts, we show that
      up to 76% of 10 cancer types harbour at least one mutation in a panel of only 25
      genes, with high sensitivity across most tumour types. Our analyses demonstrate
      that targeting "hotspot" regions would introduce biases towards in-frame
      mutations and would compromise the reproducibility of tumour detection. 

PMID- 24296835
TI  - Obinutuzumab approved for CLL: Monoclonal antibody product is first FDA-approved
      breakthrough therapy.

PMID- 24296836
TI  - Clinicians receive some support to tweak stent-related antiplatelet therapy.

PMID- 24296837
TI  - Defense Health Agency makes its debut.

PMID- 24296838
TI  - Informed consent remains a work in progress.

PMID- 24296839
TI  - Experience with a student-run patient medication assistance service.

PMID- 24296840
TI  - A new practitioner's guide to antimicrobial stewardship.

PMID- 24296841
TI  - Stability and compatibility of antimicrobial lock solutions.
AB  - PURPOSE: Published stability and compatibility data on a growing array of
      solutions used for antimicrobial lock therapy (ALT) are reviewed. SUMMARY: ALT
      involves the instillation of a highly concentrated antimicrobial, often in
      combination with an anticoagulant, into a central venous catheter (CVC) lumen;
      this technique is often used for prophylaxis after CVC insertion or as an
      adjunctive treatment in cases of central line-associated bloodstream infection
      (CLABSI) if catheter removal is not feasible. Optimal selection of stable and
      compatible antimicrobials and additives can maximize catheter dwell times,
      streamline pharmacy compounding practices, and help ensure patient safety. Of 98
      articles on ALT solutions identified in a literature search, 17 met the
      prespecified criteria for the use of validated stability and compatibility
      methodology. Antimicrobials active against common CLABSI pathogens that may be
      appropriate for ALT include cefazolin, cefotaxime, ceftazidime, ciprofloxacin,
      daptomycin, gentamicin, linezolid, telavancin, ticarcillin-clavulanic acid, and
      vancomycin; validated data demonstrate the stability of these agents in solution
      with heparin or nonheparin anticoagulants over 72-96 hours or longer. Other
      antifungal agents and antiinfectives (e.g., ethyl alcohol) have been used in
      specific patients and ALT situations. The prolonged stability of several
      antimicrobial-additive combinations may allow for extended dwell times and less
      frequent lock solution exchanges. CONCLUSION: Pharmacists' knowledge of diverse
      combinations of antimicrobial agents and additives in lock solutions, including
      several shown to be stable and compatible for extended periods, can help expand
      and optimize the use of ALT in both treatment and prophylactic modalities.

PMID- 24296842
TI  - Drug absorption in celiac disease.
AB  - PURPOSE: Published evidence on established and theorized effects of celiac
      disease on drug absorption and pharmacokinetics is reviewed. SUMMARY: Patients
      with celiac disease develop a variety of gastric disorders requiring oral
      medications, but the impact of damage to intestinal villi and other celiac
      disease sequelae on drug absorption remains poorly understood. A review of the
      pertinent literature (English-language articles on research in adults published
      during the period 1970-August 2012) identified several reports of altered drug
      absorption mechanisms in patients with celiac disease, including accelerated or
      delayed gastric emptying, increased permeability of jejunal mucosa, changes in
      intraluminal pH, decreased intestinal surface area, and reduced intestinal
      cytochrome P-450 enzymes. A small number of published studies suggest that celiac
      disease may be associated with altered drug absorption, resulting in higher serum
      concentrations of propranolol, lower peak concentrations of acetaminophen and
      practolol, higher dosing requirements with levothyroxine, impaired or delayed
      absorption of certain antibiotics, and other pharmacokinetic effects with a
      potential impact on medication efficacy and toxicity. However, these studies
      involved very small patient samples and were poorly controlled, with some
      yielding contradictory results. More and larger pharmacokinetic studies in
      patients with celiac disease-especially studies of drugs that are dosed
      empirically or are not amenable to dosage adjustment according to vital signs or
      laboratory values-are needed. CONCLUSION: Given the sometimes conflicting data on
      drug absorption in the context of celiac disease, cautious medication selection,
      dosage adjustment, and monitoring for efficacy and potential adverse effects are
      advised.

PMID- 24296843
TI  - Cost comparison of drug-drug and drug-condition interactions in patients with
      painful diabetic peripheral neuropathy treated with pregabalin versus duloxetine.
AB  - PURPOSE: The frequency and financial impact of potential drug-drug interactions
      (DDIs) and drug-condition interactions (DCIs) in patients with painful diabetic
      peripheral neuropathy (DPN) treated with either pregabalin or duloxetine were
      compared. METHODS: This retrospective cohort study was conducted using a large
      U.S. administrative claims database. Patients selected for study inclusion had a
      diagnosis of DPN and were newly initiated on either pregabalin or duloxetine
      between July 1, 2008, and October 1, 2010. Data on potential DDIs and DCIs were
      collected. Health care costs were measured as the sum of gross covered payments
      for all medical and prescription claims incurred during the six months after the
      index date. RESULTS: The study sample comprised 2499 pregabalin users and 1354
      duloxetine users. Among pregabalin users, 48 (1.8%) had at least one potential
      pregabalin DCI; none had potential pregabalin DDIs. Among duloxetine users, 966
      (71%) had at least one potential duloxetine DDI or DCI. The frequencies of
      potential DDIs and DCIs differed significantly between pregabalin and duloxetine
      users (p < 0.001). Potential duloxetine DDIs and DCIs were associated with a
      significant increase in mean health care costs in duloxetine users (p = 0.002).
      Potential pregabalin DDIs and DCIs were not associated with additional health
      care costs in pregabalin users. CONCLUSION: Among patients with painful DPN
      treated with either pregabalin or duloxetine, the frequency of potential
      duloxetine DDIs and DCIs was substantially higher than that of pregabalin.
      Potential DDIs and DCIs were associated with significantly increased health care
      costs in duloxetine users.

PMID- 24296844
TI  - Comparison of medication safety effectiveness among nine critical access
      hospitals.
AB  - PURPOSE: The rates of medication errors across three different medication
      dispensing and administration systems frequently used in critical access
      hospitals (CAHs) were analyzed. METHODS: Nine CAHs agreed to participate in this
      prospective study and were assigned to one of three groups based on similarities
      in their medication-use processes: (1) less than 10 hours per week of onsite
      pharmacy support and no bedside barcode system, (2) onsite pharmacy support for
      40 hours per week and no bedside barcode system, and (3) onsite pharmacy support
      for 40 or more hours per week with a bedside barcode system. Errors were
      characterized by severity, phase of origination, type, and cause. Characteristics
      of the medication being administered and a number of best practices were
      collected for each medication pass. Logistic regression was used to identify
      significant predictors of errors. RESULTS: A total of 3103 medication passes were
      observed. More medication errors originated in hospitals that had onsite pharmacy
      support for less than 10 hours per week and no bedside barcode system than in
      other types of hospitals. A bedside barcode system had the greatest impact on
      lowering the odds of an error reaching the patient. Wrong dose and omission were
      common error types. Human factors and communication were the two most frequently
      identified causes of error for all three systems. CONCLUSION: Medication error
      rates were lower in CAHs with 40 or more hours per week of onsite pharmacy
      support with or without a bedside barcode system compared with hospitals with
      less than 10 hours per week of pharmacy support and no bedside barcode system.

PMID- 24296845
TI  - Medication-use evaluation with a Web application.
AB  - PURPOSE: A Web-based application for coordinating medication-use evaluation (MUE)
      initiatives within the Veterans Affairs (VA) health care system is described.
      SUMMARY: The MUE Tracker (MUET) software program was created to improve VA's
      ability to conduct national medication-related interventions throughout its
      network of 147 medical centers. MUET initiatives are centrally coordinated by the
      VA Center for Medication Safety (VAMedSAFE), which monitors the agency's
      integrated databases for indications of suboptimal prescribing or drug therapy
      monitoring and adverse treatment outcomes. When a pharmacovigilance signal is
      detected, VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads
      patient lists to the secure MUET application, where locally designated personnel
      (typically pharmacists) can access and use the data to target risk-reduction
      efforts. Local data on patient-specific interventions are stored in a centralized
      database and regularly updated to enable tracking and reporting for surveillance
      and quality-improvement purposes; aggregated data can be further analyzed for
      provider education and benchmarking. In a three-year pilot project, the MUET
      program was found effective in promoting improved prescribing of erythropoiesis
      stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated
      patients in all specified trigger groups. The MUET initiative has since been
      expanded to target other high-risk drugs, and efforts are underway to refine the
      tool for broader utility. CONCLUSION: The MUET application has enabled the
      increased standardization of medication safety initiatives across the VA system
      and may serve as a useful model for the development of pharmacovigilance tools by
      other large integrated health care systems.

PMID- 24296847
TI  - Physical activity in overweight and obese pregnant women is associated with
      higher levels of proinflammatory cytokines and with reduced insulin response
      through interleukin-6.
AB  - OBJECTIVE Previously, we reported the positive association of moderate-to
      vigorous physical activity (MVPA) with insulin sensitivity in overweight and
      obese pregnant women. We sought to assess whether these MVPA-induced changes in
      insulin sensitivity are mediated by changes in interleukin (IL)-6, IL-10, tumor
      necrosis factor (TNF)-alpha, and IL-1beta. RESEARCH DESIGN AND METHODS A
      prospective longitudinal study was conducted in 46 overweight and obese women at
      risk for gestational diabetes mellitus. Objective physical activity measurements
      and fasting blood samples were taken at 15, 24, and 32 weeks of pregnancy. At 24
      and 32 weeks, a 100-g oral glucose test was performed in addition. Cytokines, C
      reactive protein, and glucose and insulin levels were measured, and insulin
      sensitivity and first-phase insulin response were calculated. Relationships
      between the different parameters were assessed using linear regression models,
      adjusting for maternal age and BMI. RESULTS All cytokines were elevated in women
      with higher levels of MVPA at 15 weeks of gestation. Higher IL-6 was related to a
      lower first-phase insulin response (beta -810.5 [95% CI -1,524.5 to -96.5]; P =
      0.03). TNF-alpha and IL-1beta had different effects in women with low MVPA (with
      low IL-6 levels) compared with more active women. CRP was not related to MVPA.
      CONCLUSIONS The association of MVPA with insulin sensitivity and first-phase
      insulin response may be (partly) mediated by IL-6, since this cytokine was
      related to reduced first-phase insulin response. The possible positive effects of
      the elevated cytokine profile in active obese pregnant women warrant further
      study. 

PMID- 24296849
TI  - Association between glycemic control and morning blood pressure surge with
      vascular endothelial dysfunction in type 2 diabetic patients.
AB  - OBJECTIVE: Morning blood pressure surge (MBPS) is an independent predictor of
      cardiovascular events. However, little is known about the association between
      glycemic control and MBPS, and its effect on vascular injury in patients with
      type 2 diabetes mellitus (T2DM). The current study examined the association
      between glycemic control and MBPS, and the involvement of MBPS in the development
      of vascular dysfunction in T2DM patients. RESEARCH DESIGN AND METHODS: We
      examined MBPS in T2DM patients (25 male patients/25 female patients; mean age,
      60.1 +/- 13.2 years; n = 50) using 24-h ambulatory blood pressure monitoring, and
      assessed vascular function by brachial artery flow-mediated dilation (FMD) and
      nitroglycerin-mediated dilation (NMD). RESULTS: HbA1c (rho = 0.373, P = 0.009)
      and triglyceride (TG) (rho = 0.375, P = 0.009) levels correlated significantly
      and positively with MBPS. In multiple regression analysis, including TG and HbA1c
      levels in addition to age and 24-h systolic blood pressure (SBP) as independent
      variables, HbA1c (beta = 0.328, P = 0.016) and TG (beta = 0.358, P = 0.014) were
      associated significantly in a positive manner with MBPS. In a noninsulin user,
      when homeostasis model assessment ratio (HOMA-R) was included in place of TG,
      HOMA-R emerged as a significant factor. MBPS (rho = -0.289, P = 0.043) and HbA1c
      (rho = -0.301, P = 0.035) correlated significantly and negatively with FMD,
      whereas 24-h SBP correlated with both FMD (rho = -0.359, P = 0.012) and NMD (rho
      = -0.478, P = 0.004). In multiple regression analysis, including age, gender, 24
      h SBP, MBPS, LDL cholesterol, and HbA1c, MBPS (beta = -0.284, P = 0.044) alone
      associated significantly in a negative manner with FMD, but not with NMD.
      CONCLUSIONS: The current study demonstrated that poor glycemic control and
      insulin resistance are independently associated with the occurrence of MBPS in
      T2DM patients, which might be significantly associated with endothelial
      dysfunction.

PMID- 24296848
TI  - Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in
      type 2 diabetes: the ACCORD Lipid Trial.
AB  - OBJECTIVE: To determine the occurrence of extremely low HDL cholesterol (HDL-C)
      among participants in the Action to Control Cardiovascular Risk in Diabetes
      (ACCORD) Lipid Trial and to examine the relationship of this finding with
      treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND
      METHODS: The ACCORD Lipid Trial was a randomized, double-blind, placebo
      controlled study conducted in patients with type 2 diabetes at 77 clinical
      centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251
      ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October
      2005 and followed until the end of study visits between 1 March and 30 June 2009.
      Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were
      treated with blinded fenofibrate or placebo on a background of simvastatin
      therapy. The main outcome measures for these descriptive, post hoc analyses was
      the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L])
      during the trial. RESULTS: Among ACCORD Lipid Trial participants, the occurrence
      of extremely low HDL-C ever during study follow-up was 106% higher among those
      randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The
      occurrence of low HDL-C was associated with concurrent treatment with fenofibrate
      and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization).
      CONCLUSIONS: Idiosyncratic and marked reduction in HDL-C can occur in some
      patients treated with both fenofibrate and TZD. Practitioners should recognize
      this important potential idiosyncratic reaction and take appropriate corrective
      action.

PMID- 24296851
TI  - A dual-energy X-ray absorptiometry scan: need to know vs nice to know.

PMID- 24296850
TI  - Costimulation modulation with abatacept in patients with recent-onset type 1
      diabetes: follow-up 1 year after cessation of treatment.
AB  - OBJECTIVE We previously reported that 2 years of costimulation modulation with
      abatacept slowed decline of beta-cell function in recent-onset type 1 diabetes
      (T1D). Subsequently, abatacept was discontinued and subjects were followed to
      determine whether there was persistence of effect. RESEARCH DESIGN AND METHODS Of
      112 subjects (ages 6-36 years) with T1D, 77 received abatacept and 35 received
      placebo infusions intravenously for 27 infusions over 2 years. The primary
      outcome-baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C
      peptide during a mixed-meal tolerance test (MMTT) at 2 years-showed higher C
      peptide with abatacept versus placebo. Subjects were followed an additional year,
      off treatment, with MMTTs performed at 30 and 36 months. RESULTS C-peptide AUC
      means, adjusted for age and baseline C-peptide, at 36 months were 0.217 nmol/L
      (95% CI 0.168-0.268) and 0.141 nmol/L (95% CI 0.071-0.215) for abatacept and
      placebo groups, respectively (P = 0.046). The C-peptide decline from baseline
      remained parallel with an estimated 9.5 months' delay with abatacept. Moreover,
      HbA1c levels remained lower in the abatacept group than in the placebo group. The
      slightly lower (nonsignificant) mean total insulin dose among the abatacept group
      reported at 2 years was the same as the placebo group by 3 years. CONCLUSIONS
      Costimulation modulation with abatacept slowed decline of beta-cell function and
      improved HbA1c in recent-onset T1D. The beneficial effect was sustained for at
      least 1 year after cessation of abatacept infusions or 3 years from T1D
      diagnosis. 

PMID- 24296852
TI  - Predicting visual outcome following surgery for idiopathic macular holes.
AB  - Since Kelly and Wendel [Arch Ophthalmol 1991;109:654-659] first reported
      successfully treating macular holes (MHs) using pars plana vitrectomy in 1991, MH
      surgery has been constantly improved. For example, introducing the removal of the
      internal limiting membrane considerably increased the closure rate of MHs, and
      the advent of microincision vitrectomy surgery reduced surgical trauma and
      decreased patient discomfort after surgery. As modern MH surgery can achieve a
      higher anatomical success rate and alleviate patients' postoperative distress,
      postoperative visual outcomes have lately become the primary concern. Informing
      patients of the expected visual acuity and visual improvement before surgery is
      ideal, but predicting postoperative visual outcomes is difficult because a large
      number of factors are associated with them. In this paper, we review previous
      studies and provide accumulating evidence for the relationship between individual
      prognostic factors and visual outcomes after MH surgery.

PMID- 24296853
TI  - Retrospective investigation of postoperative outcome after reversal of residual
      neuromuscular blockade: sugammadex, neostigmine or no reversal.
AB  - BACKGROUND: Postoperative residual neuromuscular blockade (RNMB) is associated
      with significant morbidity. OBJECTIVE: The aim of this retrospective data
      analysis was to investigate the influence of the method of RNMB reversal on
      postoperative outcome. SETTING: Tertiary teaching hospital in Western Australia.
      PATIENTS: With Ethics Committee approval, data from 1444 patients who received at
      least one dose of a non-depolarising muscle relaxant intraoperatively during 2011
      were analysed. MAIN OUTCOME MEASURES: Endpoints included unwanted events in the
      postanaesthesia care unit (PACU); symptoms of pulmonary complications within 7
      postoperative days (0 to 100 outcome score based on 'temperature >38 degrees C',
      'leucocyte count >11 * 10 l', 'physical examination consistent with pneumonia'
      and 'shortness of breath'); PACU turnover time; and length of hospital stay.
      RESULTS: Data from 1444 patients (722 sugammadex, 212 neostigmine and 510 no
      reversal) were analysed. The incidence of postoperative nausea and vomiting
      (PONV) in PACU was higher in neostigmine-reversed than sugammadex-reversed
      patients (21.5 vs. 13.6%; P <0.05). No differences were found regarding other
      PACU incidents, length of PACU stay or hospital stay. Pulmonary outcome
      deteriorated significantly (outcome score increased) with age and American
      Society of Anesthesiologists (ASA) physical status. This was observed
      particularly in ASA 3/4 patients more than 60 years of age in neostigmine
      reversed or non-reversed patients, but almost no detrimental effect of age on
      pulmonary outcome was found in the sugammadex group (P <0.05). CONCLUSION: RNMB
      reversal with sugammadex was associated with the lowest rate of PONV and may
      reduce the risk of pulmonary complications in elderly ASA 3/4 patients. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12612000087853.

PMID- 24296854
TI  - The diagnostic value of adiponectin multimers in healthy men undergoing screening
      for prostate cancer.
AB  - BACKGROUND: Adiponectin has been reported to have a prohibitory effect on
      prostate cancer. The goal of this study was to evaluate the diagnostic value of
      adiponectin multimers for prostate cancer. METHODS: Total adiponectin, high- and
      low-molecular-weight (HMW, LMW), ratios of these measures, and body mass index
      (BMI) were compared in a prospective prostate cancer-screened cohort.
      Multivariable logistic regression was used to assess the association between
      adiponectin measures, their interaction with BMI, and risk of prostate cancer and
      Gleason score upgrading from biopsy to prostatectomy. RESULTS: A total of 228
      prostate cancer cases and 239 controls were analyzed: 72 (31.6%) of the cancer
      cases were high grade (Gleason grade >=7). Only percent HMW had a statistically
      significant relationship with prostate cancer (P = 0.04). Among normal and
      overweight men, the risk of prostate cancer increased as percent HMW increased
      [OR = 1.24 for a doubling of percent HMW, 95% confidence interval (CI), 0.41-3.75
      and OR = 1.81; 95% CI, 1.02-3.20, respectively], whereas among obese men, the
      risk of prostate cancer decreased (OR = 0.62; 95% CI, 0.32-1.18). Among 97
      patients who underwent radical prostatectomy, there was no association between
      Gleason score upgrading and any of the adiponectin multimers. CONCLUSION: This
      study was unable to confirm the utility of total adiponectin as a biomarker for
      prostate cancer risk. For the adiponectin multimers, only HMW showed increases
      with prostate cancer but not in all weight classes. IMPACT: Although adiponectin
      may play a role in the pathogenesis of prostate cancer, our results do not
      support adiponectin multimers as biomarkers of detection.

PMID- 24296855
TI  - Risk factors for early childhood infection of human herpesvirus-8 in Zambian
      children: the role of early childhood feeding practices.
AB  - BACKGROUND: Human herpesvirus-8 (HHV-8) infection in early childhood is common
      throughout sub-Saharan Africa with prevalence increasing throughout childhood.
      Specific routes of transmission have not been clearly delineated, though HHV-8 is
      present in high concentrations in saliva. METHODS: To understand the horizontal
      transmission of HHV-8 within households to children, we enrolled for cross
      sectional analysis, 251 households including 254 children, age two and under, in
      Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV type I
      (HIV-1) and health and behavioral questionnaires were completed. Multilevel
      logistic regression analysis was conducted to assess independent factors for HHV
      8 infection in children. RESULTS: Risk factors for HHV-8 infection included
      increasing number of HHV-8-positive household members [OR = 2.5; 95% confidence
      interval (CI), 1.9-3.3; P < 0.01] and having a primary caregiver who tested the
      temperature of food with their tongue before feeding the child (OR = 2.4; 95% CI,
      1.93-3.30; P = 0.01). Breastfeeding was protective against infection with HHV-8
      for children (OR = 0.3; 95% CI, 0.16-0.72; P < 0.01). CONCLUSIONS: These results
      indicate that exposure to HHV-8 in the household increases risk for early
      childhood infection, with specific feeding behaviors likely playing a role in
      transmission. IMPACT: Interventions to protect children from infection should
      emphasize the possibility of infection through sharing of foods.

PMID- 24296857
TI  - Access to the Indian health service care system is not associated with early
      enrollment in medicaid for American Indian and Alaska Natives with cancer.
AB  - BACKGROUND: For uninsured American Indians and Alaskan Natives (AIAN) diagnosed
      with cancer, prompt enrollment in Medicaid may speed access to treatment and
      improve survival. We hypothesized that AIANs who were eligible for the Indian
      Health Service Care System (IHSCS) at cancer diagnosis may be enrolled in
      Medicaid sooner than other AIANs. METHODS: Using Washington, Oregon, and
      California State Cancer Registries, we identified AIANs with a primary diagnosis
      of lung, breast, colorectal, cervical, ovarian, stomach, or prostate cancer
      between 2001 and 2007. Among AIANs enrolled in Medicaid within 365 days of a
      cancer diagnosis, we linked cancer registry records with Medicaid enrollment data
      and used a multivariate logistic regression model to compare the odds of delayed
      Medicaid enrollment between those with (n = 223) and without (n = 177) IHSCS
      eligibility. RESULTS: Among AIANs who enrolled in Medicaid during the year
      following their cancer diagnosis, approximately 32% enrolled >1 month following
      diagnosis. Comparing those without IHSCS eligibility to those with IHSCS
      eligibility, the adjusted odds ratio (OR) for moderately late Medicaid enrollment
      (between 1 and 6 months after diagnosis) relative to early Medicaid enrollment
      (<=1 month after diagnosis) was 1.10 [95% confidence interval (CI), 0.62-1.95]
      and for very late Medicaid enrollment (>6 months to 12 months after diagnosis),
      OR was 1.14 (CI, 0.54-2.43). CONCLUSION: IHSCS eligibility at the time of
      diagnosis does not seem to facilitate early Medicaid enrollment. IMPACT: Because
      cancer survival rates in AIANs are among the lowest of any racial group,
      additional research is needed to identify factors that improve access to care in
      AIANs.

PMID- 24296856
TI  - Differences in gene and protein expression and the effects of race/ethnicity on
      breast cancer subtypes.
AB  - BACKGROUND: Differences in gene or protein expression patterns between breast
      cancers according to race/ethnicity and cancer subtype. METHODS: Transcriptional
      profiling was performed using Affymetrix HG-U133A platform in 376 patients and
      reverse phase protein array analysis (RPPA) was done for 177 proteins in 255
      patients from a separate cohort. Unsupervised clustering was conducted, as well
      as supervised comparison by race and tumor subtype. Standard statistical methods,
      BRB-Array tools, and Ingenuity Pathways software packages were used to analyze
      the data. RESULTS: Median age was 50 years in both the cohorts. In the RPPA
      cohort, 54.5% of the tumors were hormone receptor-positive (HR-positive), 20.7%
      HER2-positive, and 24.71% triple-negative (TNBC). One hundred and forty-seven
      (57.6%), 47 (18.43%), and 46 (18.1%) of the patients were White, Hispanic, and
      Black, respectively. Unsupervised hierarchical clustering of the protein
      expression data showed no distinct clusters by race (P values were 0.492, 0.489,
      and 0.494 for the HR-positive, HER2-positive, and TNBC tumors respectively). In
      the gene expression cohort, 54.2% of the tumors were HR-positive, 16.5% HER2
      positive, and 29.3% TNBC. Two hundred and sixteen (57.5%), 111 (29.52%), and 32
      (8.52%) patients were White, Hispanic, and Black, respectively. No probe set with
      a false discovery rate (FDR) of <0.05 showed an association with race by breast
      cancer subtype; similar results were obtained using pathway and gene set
      enrichment analysis methods. CONCLUSIONS: We did not detect a significant
      variation in RNA or protein expression comparing different race/ethnicity groups
      of women with breast cancer. IMPACT: More research on the complex network of
      factors that result in outcomes differences among race/ethnicities is needed.

PMID- 24296858
TI  - An older woman after a first generalized seizure. Primary central nervous system
      lymphoma of the B cell.

PMID- 24296859
TI  - Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation,
      heat shock protein 27 phosphorylation, and cell cycle: role and targeting.
AB  - Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK-2 or
      MK2) is a downstream substrate of the p38 MAPK responsible for the signaling
      events influencing inflammation, cell division and differentiation, apoptosis,
      and cell motility in response to a wide range of extracellular stimuli. After the
      failure of p38 MAPK inhibitors in clinical trials, MK2 was unveiled as a
      potential target to regulate inflammatory cytokines' mRNA stability and
      translation. Recent work suggests that this mechanism may underlie the
      pathophysiology of brain disorders associated with inflammation. In addition, MK2
      is a prominent kinase that phosphorylates heat shock protein 27 (Hsp27), an
      intensively investigated biomarker of cancer progression. This phosphorylation
      decreases the chaperone properties of Hsp27, making MK2 an endogenous inhibitor
      of Hsp27. MK2 is also one of the major players in the signal transduction
      pathways activated in response to DNA damage. Experimental evidence highlights
      the role of MK2 in G(2)/M and the mitotic spindle checkpoints, two mechanisms by
      which MK2 contributes to the maintenance of genomic stability. Thus, MK2 is
      considered a good molecular target to increase, in combination with
      chemotherapeutic agents, the sensitivity of treatment, especially in p53-mutated
      tumors. This review looks at the functions of MK2 in inflammation, Hsp27
      regulation, and cell cycle checkpoint control with a focus on brain pathologies.
      Analysis of MK2 signaling in various disease models and a summary of the data on
      MK2 inhibitors suggest novel indications for MK2 inhibitors in addition to their
      mainstream use against peripheral inflammatory disorders.

PMID- 24296860
TI  - Enteral nutrition in the critically ill: myths and misconceptions.
AB  - BACKGROUND: Nutritional support is an essential component of the management of
      critically ill and injured ICU patients. Optimal provision of calories and
      protein has been demonstrated to reduce morbidity, mortally, and length of ICU
      and hospital stay. Yet, a large proportion of ICU patients receive inadequate
      nutrition. OBJECTIVE: To provide an evidence-base assessment of factors leading
      to inadequate enteral nutrition support in critically ill patients. DATA SOURCE:
      Search of PubMed database and manual review of bibliographies from selected
      articles. DATA SYNTHESIS AND CONCLUSIONS: A number of common myths and
      misconceptions appear to play a major role in limiting the provision of enteral
      nutrition in the critically ill. This article provides scientific data to debunk
      the most common myths and misconceptions related to enteral nutrition.

PMID- 24296861
TI  - Facile preparation of transparent and dense CdS-silica gel glass nanocomposites
      for optical limiting applications.
AB  - To realize their practical and operable applications as a potential optical
      limiting (OL) material, quantum dots (QDs) need to have good processability by
      incorporating them into optical-quality matrices. This work reports a facile
      route for the room-temperature preparation of large, stable transparent
      monolithic CdS nanocomposites which can be easily extended to allow the
      introduction of acid-sensitive functional molecules/nanoparticles into a silica
      network by sol-gel chemistry. Our strategy involves a two-step sol-gel process
      (acid-catalyst hydrolysis and basic-catalyst condensation) and the co
      condensation of the resulting alkoxysilane-capped CdS QDs with other
      alkoxysilanes, which allows the CdS QDs to become part of the silica covalent
      network. The degradation and agglomeration of CdS QDs were thereby effectively
      restrained, and large monolithic transparent CdS-silica gel glass was obtained.
      Using Z-scan theory and the resulting open-aperture Z-scan curves, the nonlinear
      extinction coefficient of the CdS-silica nanocomposite gel glass was calculated
      to be 1.02 * 10(-14) cm W(-1), comparable to that of the parent CdS QD
      dispersion, indicating their promise for OL applications. 

PMID- 24296862
TI  - Rapid detection for rabbit-derived dermatophytes using microsatellite-primed
      polymerase chain reaction.
AB  - A method exhibiting high sensitivity, specificity and rapidity to detect
      pathogenic dermatophytes was developed using microsatellite-primed polymerase
      chain reaction (PCR) in combination with a clustering method. The DNA fragments
      of Trichophyton mentagrophyton, Microsporum gypseum and Microsporum canis were
      amplified by using the primer (GACA)4 to detect the DNA polymorphism
      fingerprints. Twenty-one clinical strains identified as T. mentagrophyton, M.
      gypseum or M. canis by morphological methods were distinguished according to the
      differences of standard stains' bands combined with NTSYS-pc2.10 software. The
      results showed that there were obvious and direct differences in the bands of the
      three pathogenic dermatophytes, and the similarity of isolated strains and
      standard strains were above 90%, in line with the results of morphological
      identification. The method is more accurate, rapid and simple, which is
      meaningful for the clinical diagnosis and epidemic research of the dermatophytes.

PMID- 24296863
TI  - Insights and perspectives on emerging inputs to weight of evidence determinations
      for food safety: workshop proceedings.
AB  - This workshop aimed to elucidate the contribution of computational and emerging
      in vitro methods to the weight of evidence used by risk assessors in food safety
      assessments. The following issues were discussed: using in silico and high
      throughput screening (HTS) data to confirm the safety of approved food
      ingredients, applying in silico and HTS data in the process of assessing the
      safety of a new food ingredient, and utilizing in silico and HTS data in
      communicating the safety of food ingredients while enhancing the public's trust
      in the food supply. Perspectives on integrating computational modeling and HTS
      assays as well as recommendations for optimizing predictive methods for risk
      assessment were also provided. Given the need to act quickly or proceed
      cautiously as new data emerge, this workshop also focused on effectively
      identifying a path forward in communicating in silico and in vitro data. 

PMID- 24296864
TI  - Risk assessment of free hydroquinone derived from Arctostaphylos Uva-ursi folium
      herbal preparations.
AB  - Uva-ursi folium (bearberry leaf) has been traditionally used to treat symptoms of
      lower urinary tract infections. The most representative constituent of this
      herbal drug is arbutin that is rapidly absorbed in the small intestine and
      undergoes hepatic conjugation to form hydroquinone (HQ) conjugates. As free HQ is
      crucial for the safety of the herbal preparation, we reviewed published and
      unpublished experimental and human studies to clarify some outdated assumptions
      and to support the safety of therapeutic daily doses of Uva-ursi folium extract.
      Specifically, data on pharmacokinetics and the human exposure of arbutin and HQ
      were reviewed. A therapeutic recommended human daily dose of bearberry leaf
      extract (420 mg hydroquinone derivatives calculated as anhydrous arbutin)
      liberates free HQ in urine at a maximum exposure level of 11 ug/kg body weight
      (bw)/d. By means of an experimental no observed effect level value, a permitted
      daily exposure dose below which there is a negligible risk to human health was
      estimated for free HQ (100 ug/kg bw/d). Dietary sources of arbutin/HQ that are
      regularly consumed long term by humans generate comparable free HQ exposure
      levels. There is no direct evidence, regarding human data, supporting the fact
      that free HQ causes convulsion, hepatotoxicity, nephrotoxicity, or promotion of
      tumors in humans. Free HQ had no activity promoting pancreatic, bladder, stomach,
      or liver carcinogenesis. In conclusion, under the recommended use conditions Uva
      ursi folium is a safe therapeutic option for treating lower urinary tract
      infections. 

PMID- 24296866
TI  - A mild and catalyst-free conversion of solid phase
      benzylidenemalononitrile/benzylidenemalonate to N-benzylidene-amine and its
      application for fluorescence detection of primary alkyl amine vapor.
AB  - A new rapid and catalyst-free solid/vapor reaction between
      benzylidenemalonate/benzylidenemalononitrile and primary alkyl amines was found.
      With these as sensory units of fluorescent polymers, probes for primary amine
      vapor with high sensitivity and selectivity were developed. 

PMID- 24296865
TI  - Parkinson's disease mild cognitive impairment: application and validation of the
      criteria.
AB  - Dementia in Parkinson's disease (PD) is a serious health issue and a major
      concern for many patients. In most cases mild cognitive impairment (MCI) is
      considered a transitional stage between normal cognitive functioning and dementia
      which is of potential importance in the early identification of patients at risk
      for dementia. Recently, the Movement Disorder Society (MDS) proposed diagnostic
      criteria for MCI in PD (PD-MCI). These criteria comprise two operationalizations:
      Level I (based on an abbreviated assessment) and Level II (based on comprehensive
      neuropsychological evaluation permitting MCI subtyping). These criteria need to
      be validated. This paper describes a project aiming to validate the MDS PD-MCI
      criteria by pooling and analyzing cross-sectional and longitudinal
      neuropsychological databases comprising >=5,500 PD patients and >=1,700 controls.
      After applying the MDS PD-MCI Level I and Level II criteria, rates of conversion
      to PD-dementia and predictive variables for conversion to PD-dementia will be
      established. This study will also assist in identifying whether revisions of the
      PD-MCI criteria are required. 

PMID- 24296867
TI  - Vitamin K status in healthy volunteers.
AB  - Vitamin K's recommended dietary allowance (RDA) is based on the hepatic
      requirement for clotting factor synthesis, but substantial concentrations of
      undercarboxylated extra-hepatic Gla-proteins are found in the circulation of non
      supplemented individuals. This suggests that vitamin K intake above the RDA is
      required for an optimal extra-hepatic vitamin K status. Circulating
      uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla
      protein (dp-ucMGP) are considered markers of the vitamin K status in bone and the
      vasculature, respectively. We measured these markers in 896 samples of healthy
      volunteers and defined target groups for vitamin K supplementation based on
      increased levels indicative of tissue-specific vitamin K deficiency. We studied
      the response to vitamin K supplements at different states of vitamin K deficiency
      by measuring the circulating dp-ucMGP level in samples from two short-term trials
      on menaquinone-7 (MK-7, vitamin K2) supplementation in 42 children and 68 adults.
      Children had high ucOC levels (3.4-96.9 ng ml(-1)); other age groups had values
      in the range of 1.5-5.0 ng ml(-1). From the age of 40 years, dp-ucMGP levels
      gradually increased. Children and adults with more pronounced vitamin K
      deficiency gave the highest responses to MK-7 supplementation. Children and
      adults above 40 years showed the largest tissue-specific vitamin deficiency and
      accordingly may benefit from MK-7 supplementation to improve their extra-hepatic
      vitamin K status. 

PMID- 24296868
TI  - Improved photoluminescence and sensing stability of porous silicon nanowires by
      surface passivation.
AB  - Core-shell structured silicon nanowires (Si NWs) were obtained by coating Si NWs
      with an HfO2 layer. Enhanced photoluminescence (PL) and a slightly decreased PL
      lifetime are achieved by HfO2 coating. Furthermore, the sensing stability is
      strongly improved. The improvement of PL properties is interpreted in terms of
      surface passivation and the Purcell effect. 

PMID- 24296869
TI  - Ivabradine improves quality of life in subjects with chronic heart failure
      compared to treatment with beta-blockers: results of a multicentric observational
      APULIA study.
AB  - OBJECTIVES: Ivabradine (IVA), a selective If current inhibitor decreasing the
      heart rate (HR) in patients with sinus rhythm, has been added to the most recent
      European Guidelines on heart failure. This selective treatment reduces HR
      exclusively while fully preserving myocardial contractility and relaxation,
      atrioventricular conduction, and ventricular repolarization, as well as blood
      pressure. The aim of this study was to evaluate the improvement of quality of
      life (QOL) in patients with chronic heart failure (CHF) treated with IVA versus
      two beta-blockers (bisoprolol and carvedilol). METHODS: We evaluated if a 1-month
      treatment with IVA (5 mg b.i.d.) or beta-blockers (carvedilol 6.25 mg b.i.d. or
      bisoprolol 1.25 mg b.i.d.) improves the QOL (assessed by SF-36 questionnaire) in
      patients with CHF with reduced left ventricular ejection fraction (<50%). SF-36
      was tested in 221 CHF patients (mean age 64 +/- 6 years) randomized into two
      groups (IVA group - 110 patients; beta-blockers group - 111 patients). Data of
      QOL questionnaire and HR were collected by an interview during a clinical visit
      both at prescription time (basal) and after 1 month of therapy with IVA or beta
      blockers. QOL life and HR results after 1-month of therapy (T1) with IVA were
      compared with basal values (T0). RESULTS: The IVA versus beta-blockers treatment
      was associated with a significant improvement of physical functioning (p < 0.001
      vs. p < 0.01), physical role functioning (p < 0.001 vs. p < 0.01), emotional role
      functioning (p < 0.01 vs. p < 0.85), and mental health scales (p < 0.001 vs. p <
      0.01). HR in the IVA group was significantly lower compared to the group of
      patients treated with beta-blockers (63 vs. 67 bpm; p < 0.001). CONCLUSIONS: IVA
      treatment significantly improves the QOL in patients with CHF without any
      deleterious impact on hemodynamics, and may be beneficial in these patients
      without other adverse effects associated with beta-blockers.

PMID- 24296870
TI  - Changing the narrative for early childhood investment.

PMID- 24296871
TI  - Allopurinol as a preventive contrivance after acute ischemic stroke in patients
      with a high level of serum uric acid: a randomized, controlled trial.
AB  - OBJECTIVES: To assess the clinical relevance (functional outcome) of a 3-month
      allopurinol regimen in patients with high serum uric acid (SUA) levels and acute
      ischemic stroke without considering the changes in SUA levels. MATERIALS AND
      METHODS: In a randomized, double-blind, controlled study, 70 patients (45
      females, 25 males) with acute ischemic stroke who had elevated levels of SUA were
      included. They were divided in two 35-patient groups to investigate the effect of
      3 months of an allopurinol (200 mg/day) regimen versus placebo on their
      functional outcome, which was evaluated using a modified Rankin scale. RESULTS:
      The overall mean age was 68.9 +/- 11.33 years (range 27-89). The final favorable
      functional status (mRS = 0-2) was 23 (65.7%) and 14 (40.0%) in the treated and
      placebo groups, respectively, which was strongly associated with allopurinol
      consumption (OR = 4.646, p = 0.014) and age <=70 years (OR = 0.139, p = 0.005) in
      patients with ischemic stroke after adjusting for confounders. There was no
      significant difference in death between allopurinol-treated cases (3; 8.6%) and
      placebo-treated ones (6; 17.2%; p = 0.278). CONCLUSION: Allopurinol treatment was
      well tolerated and improved the 3-month functional status of patients with acute
      ischemic stroke who had high levels of SUA without considering the decreasing
      effect of allopurinol on SUA.

PMID- 24296872
TI  - Evolutionary dynamics of repetitive DNA in semaprochilodus (characiformes,
      prochilodontidae): a fish model for sex chromosome differentiation.
AB  - Distribution of 6 microsatellites and 5 transposable elements on the chromosomes
      of Semaprochilodus taeniurus and S. insignis, commonly referred to as Jaraqui,
      was performed using their physical mapping with fluorescence in situ
      hybridization. In this study, we aim to understand the evolutionary dynamics in
      genomes of S. taeniurus and S. insignis by comparing the position, abundance and
      contribution of the repetitive sequences in the origins and differentiation of a
      ZZ/ZW sex chromosome system in S. taeniurus. Results revealed that distribution
      patterns of repetitive DNAs along the chromosomes varied considerably.
      Hybridization signals were observed on several autosomes in both species;
      however, in S. taeniurus genome, the repetitive sequences were more abundant. In
      addition, large clusters of known repetitive sequences were detected in sex
      chromosomes of S. taeniurus. This observation is notable because the accumulation
      of repetitive DNAs could reflect the degradation of genetic activities and the
      differentiation of protosex chromosomes, evolving into the heteromorphic ZW pair
      observed in S. taeniurus.

PMID- 24296873
TI  - Nocturnal deterioration after ischemic stroke and autonomic dysfunction:
      hypothesis and implications.
AB  - BACKGROUND: A significant number of patients admitted to hospital after acute
      ischemic stroke deteriorate clinically. Deterioration is generally noted within
      the first 48 h after stroke onset. The mechanisms leading to this deterioration
      are not fully understood. SUMMARY: One potential cause of this deterioration may
      be altered or impaired autonomic function. We expect the hemodynamic changes
      regulated by the autonomic nervous system that are dysregulated after stroke to
      be exaggerated during sleep, resulting in arrhythmia and blood pressure
      fluctuations in these patients. Such physiological changes could result in
      worsening the overall outcome of the ischemic stroke patient or in sudden death.
      Therefore, it is necessary to summarize yet unrelated observations and
      hypothesize on their individual effects and interactions as they relate to
      poststroke deterioration. KEY MESSAGES: If the hypothesis is correct that
      dysautonomia occurs to the degree that it affects clinical outcomes negatively,
      this would have important implications for the prevention of neurological
      deterioration and sudden death after ischemic stroke.

PMID- 24296875
TI  - Transfer of obese patients in European air ambulances.
AB  - The prevalence of obesity is rising worldwide. To investigate how fixed-wing air
      ambulances handle bariatric transfers, we conducted a survey addressing
      logistical and medical issues. A questionnaire was sent to 24 air ambulance
      companies in Europe. Seventy-nine percent of European companies returned the
      questionnaire, 95% of the companies consider the transfer of heavyweight patients
      challenging, and 21% have experienced critical incidents related to the patient's
      obesity. Forty-seven percent have standard operating procedures in place for
      bariatric transports. Only 26% will dispatch extra personnel for such flights.
      Dedicated tools for transferring, bedding, and securing patients are available
      very inconsistently. Medical provisions such as airway management, monitoring,
      and vascular access for the obese reach high standards. While medical resources
      for obesity-related problems reach a high standard, poor logistical preparations
      could lead to harm for patient and medical escort alike. 

PMID- 24296876
TI  - The paediatric psychiatric emergency population in a university teaching hospital
      in Belgium (2003-2008).
AB  - In the last few decades, there has been a remarkable increase in the number of
      children and adolescents presenting with psychiatric complaints to the emergency
      department in the USA. In Europe, however, less is known about the paediatric
      psychiatric emergency population. This study provides a clinical and demographic
      profile of this population and its service use in a European context. From 2003
      to 2008, we registered 989 paediatric psychiatric patients consulting the
      psychiatric emergency services (PES) of a large university hospital in Belgium.
      During this period the number of patients increased more than three-fold.
      Patients were predominantly female (57.3%) and adolescent (83.3%) and mostly
      referred for hostility and violence towards others (18.5%) and suicidal ideation
      (17.8%). For about 1/4 of the patients, PES was the first ever mental health
      treatment contact. PES could serve as a place for early detection and
      intervention and as an entry point to mental health services. 

PMID- 24296877
TI  - Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in
      normal and fibrotic human liver.
AB  - Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic
      cells in many organs, including hepatic stellate cells. As yet, there is no
      specific marker with which to distinguish stellate cells from myofibroblasts in
      the human liver. To investigate whether CYGB can be utilized to distinguish
      hepatic stellate cells from myofibroblasts in normal and fibrotic human liver,
      human liver tissues damaged by infection with hepatitis C virus (HCV) and at
      different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry
      was performed on histological sections of liver tissues using antibodies against
      CYGB, cellular retinol-binding protein-1 (CRBP-1), alpha-smooth muscle actin
      (alpha-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2).
      CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in
      histological sections of the samples. The expression of several of the proteins
      listed above was examined in cultured mouse stellate cells. Quiescent stellate
      cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal
      livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and
      alpha-SMA, whereas myofibroblasts around the portal vein expressed alpha-SMA, Thy
      1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively
      correlated with increases in Sirius red-stained, alpha-SMA-positive, and Thy-1
      positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased
      with fibrosis development. Primary cultured mouse stellate cells expressed
      cytoplasmic CYGB at day 1, whereas they began to express alpha-SMA at the
      cellular margins at day 4. Thy-1 was undetectable throughout the culture period.
      In human liver tissues, quiescent stellate cells are CYGB positive. When
      activated, they also become alpha-SMA positive; however, they are negative for
      Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate
      cells from portal myofibroblasts in the damaged human liver. 

PMID- 24296878
TI  - Hepatic stellate cells promote tumor progression by enhancement of
      immunosuppressive cells in an orthotopic liver tumor mouse model.
AB  - The immunosuppressive properties of hepatic stellate cells (HSCs) contribute to
      the occurrence and development of hepatocellular carcinoma (HCC). The
      accumulation of cells with immune suppressive activities, such as myeloid-derived
      suppressor cells (MDSCs) and regulatory T cells (Tregs) is a key mechanism for
      tumor immune evasion. However, the impact of HSCs on immune cell populations in
      tumor-bearing hosts is unclear. In this study, we established an orthotopic liver
      tumor mouse model for studying the complex tumor-host interactions in HCC. The
      activated HSCs promoted HCC growth not only induced tumor angiogenesis and
      lymphangiogenesis, but also significantly increased the suppressive immune cell
      population of Tregs and MDSCs in the spleen, bone marrow, and tumor tissues of
      the tumor-bearing mice. Murine HCC cell line H22-activated HSCs also expanded the
      expression of Tregs and MDSCs in vitro. In conclusion, our study suggests a novel
      role for HSCs in the HCC microenvironment. HSCs can promote HCC progression by
      enhancement of the immunosuppressive cell population. Targeting HSCs, which is a
      new concept in adjuvant immunotherapy, may be introduced in the near future to
      improve the outcome of patients with HCC. 

PMID- 24296880
TI  - Dramatic synergistic effects between hydroquinone and resorcinol derivatives for
      the organocatalyzed reduction of dioxygen by diethylhydroxylamine.
AB  - Diethylhydroxylamine reduces dioxygen in the presence of catalytic amounts of
      hydroquinone. A great improvement is achieved by adding resorcinol derivatives as
      co-catalysts. Though the formation of heterodimers does not seem to be the sole
      cause of the synergy, such products constitute a new class of powerful
      organocatalysts for dioxygen scavenging. 

PMID- 24296879
TI  - Optimization and comprehensive characterization of a faithful tissue culture
      model of the benign and malignant human prostate.
AB  - Few preclinical models accurately depict normal human prostate tissue or primary
      prostate cancer (PCa). In vitro systems typically lack complex cellular
      interactions among structured prostatic epithelia and a stromal microenvironment,
      and genetic and molecular fidelity are concerns in both in vitro and in vivo
      models. 'Tissue slice cultures' (TSCs) provide realistic preclinical models of
      diverse tissues and organs, but have not been fully developed or widely utilized
      for prostate studies. Problems encountered include degeneration of differentiated
      secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we
      optimized, characterized, and applied a TSC model of primary human PCa and benign
      prostate tissue that overcomes many deficiencies of current in vitro models.
      Tissue cores from fresh prostatectomy specimens were precision-cut at 300 MUm and
      incubated in a rotary culture apparatus. The ability of varied culture conditions
      to faithfully maintain benign and cancer cell and tissue structure and function
      over time was evaluated by immunohistological and biochemical assays. After
      optimization of the culture system, molecular and cellular responses to androgen
      ablation and to piperlongumine (PL), purported to specifically reduce androgen
      signaling in PCa, were investigated. Optimized culture conditions successfully
      maintained the structural and functional fidelity of both benign and PCa TSCs for
      5 days. TSCs exhibited androgen dependence, appropriately undergoing ductal
      degeneration, reduced proliferation, and decreased prostate-specific antigen
      expression upon androgen ablation. Further, TSCs revealed cancer-specific
      reduction of androgen receptor and increased apoptosis upon treatment with PL,
      validating data from cell lines. We demonstrate a TSC model that authentically
      recapitulates the structural, cellular, and genetic characteristics of the benign
      and malignant human prostate, androgen dependence of the native tissue, and
      cancer-specific response to a potentially new therapeutic for PCa. The work
      described herein provides a basis for advancing the experimental utility of the
      TSC model. 

PMID- 24296881
TI  - Immunopathological significance of ovarian teratoma in patients with anti-N
      methyl-d-aspartate receptor encephalitis.
AB  - BACKGROUND: The clinical importance of ovarian teratoma in anti-N-methyl-D
      aspartate receptor (NMDAR) encephalitis has been established, however
      investigations of ovarian teratoma in patients with anti-NMDAR encephalitis
      remain limited. OBJECTIVE: To clarify differences in NMDAR distribution and
      lymphocyte infiltration in ovarian teratoma between patients with and without
      anti-NMDAR encephalitis. METHODS: Participants initially comprised 26 patients
      with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian
      teratomas were examined using immunopathological techniques. Clinical,
      laboratory, and radiological data were compared between patients showing the
      features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal
      fluid were also measured in encephalitis patients. RESULTS: Neuronal tissues were
      obtained from ovarian teratomas in 22 patients (after excluding 4 patients who
      did not satisfy the inclusion criteria), and the presence of NMDA receptor
      subunits was revealed in all patients. Lymphocyte infiltration was more frequent
      in the encephalitis group (n = 3) than in the non-encephalitis group. In
      particular, dense B-lymphocyte infiltration near neural tissues was observed in
      the encephalitis group. CONCLUSIONS: Differences in lymphocyte infiltration in
      ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients
      suggest the immunological importance of the ovarian teratoma as the site of
      antigen presentation in anti-NMDAR encephalitis.

PMID- 24296882
TI  - Single-cell force spectroscopy of pili-mediated adhesion.
AB  - Although bacterial pili are known to mediate cell adhesion to a variety of
      substrates, the molecular interactions behind this process are poorly understood.
      We report the direct measurement of the forces guiding pili-mediated adhesion,
      focusing on the medically important probiotic bacterium Lactobacillus rhamnosus
      GG (LGG). Using non-invasive single-cell force spectroscopy (SCFS), we quantify
      the adhesion forces between individual bacteria and biotic (mucin, intestinal
      cells) or abiotic (hydrophobic monolayers) surfaces. On hydrophobic surfaces,
      bacterial pili strengthen adhesion through remarkable nanospring properties,
      which - presumably - enable the bacteria to resist high shear forces under
      physiological conditions. On mucin, nanosprings are more frequent and adhesion
      forces larger, reflecting the influence of specific pili-mucin bonds.
      Interestingly, these mechanical responses are no longer observed on human
      intestinal Caco-2 cells. Rather, force curves exhibit constant force plateaus
      with extended ruptures reflecting the extraction of membrane nanotethers. These
      single-cell analyses provide novel insights into the molecular mechanisms by
      which piliated bacteria colonize surfaces (nanosprings, nanotethers), and offer
      exciting avenues in nanomedicine for understanding and controlling the adhesion
      of microbial cells (probiotics, pathogens). 

PMID- 24296883
TI  - (18)F-FDG PET/CT in the management of patients with post-transplant
      lymphoproliferative disorder.
AB  - OBJECTIVES: Post-transplant lymphoproliferative disorder (PTLD) is a rare but
      serious complication in transplant patients. Although fluorine-18 2-fluoro-2
      deoxyglucose PET and computed tomography ((18)F-FDG PET/CT) has been used for the
      evaluation and management of patients with PTLD, its utility has yet to be
      documented. We were therefore prompted to review our experience with (18)F-FDG
      PET/CT in PTLD. MATERIALS AND METHODS: We retrospectively reviewed the records of
      consecutive patients who had undergone (18)F-FDG PET/CT for evaluation of PTLD
      from January 2004 to June 2012 at our institution. (18)F-FDG PET/CT scans were
      compared with other imaging modalities performed concurrently. A chart review of
      pertinent clinical information was also conducted. RESULTS: A total of 30
      patients were identified (14 female and 16 male; 1.7-76.7 years of age, average:
      23.8 years). Twenty-seven participants had biopsy-proven PTLD and another three
      had been treated for PTLD because of high clinical suspicion of disease and
      positive (18)F-FDG PET/CT findings in the absence of histological diagnosis.
      Eighty-three percent of these PTLD patients had extranodal involvement. In 57% of
      the cases, (18)F-FDG PET/CT detected occult lesions not identified on other
      imaging modalities or suggested PTLD in equivocal lesions. The more aggressive
      PTLD histological subtypes demonstrated higher SUVmax compared with the less
      aggressive subtypes. CONCLUSION: (18)F-FDG PET/CT is beneficial in the diagnostic
      evaluation of patients with PTLD. (18)F-FDG PET/CT has the ability to detect
      occult lesions not identified on other imaging modalities, particularly
      extranodal lesions. In addition, (18)F-FDG PET/CT may predict the PTLD subtype,
      as the lesions with higher pathologic grade presented with significantly higher
      SUVmax compared with the less aggressive forms.

PMID- 24296884
TI  - Case studies, case series and biological plausibility.

PMID- 24296885
TI  - Influence of gaze and directness of approach on the escape responses of the
      Indian rock lizard, Psammophilus dorsalis (Gray, 1831).
AB  - Animals often evaluate the degree of risk posed by a predator and respond
      accordingly. Since many predators orient their eyes towards prey while attacking,
      predator gaze and directness of approach could serve as conspicuous indicators of
      risk to prey. The ability to perceive these cues and discriminate between high
      and low predation risk should benefit prey species through both higher survival
      and decreased energy expenditure. We experimentally examined whether Indian rock
      lizards (Psammophilus dorsalis) can perceive these two indicators of predation
      risk by measuring the variation in their fleeing behaviour in response to type of
      gaze and approach by a human predator. Overall, we found that the gaze and
      approach of the predator influenced flight initiation distance, which also varied
      with attributes of the prey (i.e. size/sex and tail-raise behaviour). Flight
      initiation distance (FID) was 43 percent longer during direct approaches with
      direct gaze compared with tangential approaches with averted gaze. In further,
      exploratory, analyses, we found that FID was 23 percent shorter for adult male
      lizards than for female or young male (FYM) lizards. In addition, FYM lizards
      that showed a tail-raise display during approach had a 71 percent longer FID than
      those that did not. Our results suggest that multiple factors influence the
      decision to flee in animals. Further studies are needed to test the generality of
      these factors and to investigate the proximate mechanisms underlying flight
      decisions.

PMID- 24296886
TI  - Influence of clove oil on certain quorum-sensing-regulated functions and biofilm
      of Pseudomonas aeruginosa and Aeromonas hydrophila.
AB  - Quorum sensing (QS) plays an important role in virulence, biofilm formation and
      survival of many pathogenic bacteria including Pseudomonas aeruginosa. This
      signalling pathway is considered as novel and promising target for anti-infective
      agents. In the present investigation, effect of the Sub-MICs of clove oil on QS
      regulated virulence factors and biofilm formation was evaluated against P.
      aeruginosa PAO1 and Aeromonas hydrophila WAF-38 strain. Sub-inhibitory
      concentrations of the clove oil demonstrated statistically significant reduction
      of las- and rhl-regulated virulence factors such as LasB, total protease,
      chitinase and pyocyanin production, swimming motility and exopolysaccharide
      production. The biofilm forming capability of PAO1 and A. hydrophila WAF-38 was
      also reduced in a concentration-dependent manner at all tested sub-MIC values.
      Further, the PAO1-preinfected Caenorhabditis elegans displayed an enhanced
      survival when treated with 1.6 percent v/v of clove oil. The above findings
      highlight the promising anti-QS-dependent therapeutic function of clove oil
      against P. aeruginosa.

PMID- 24296887
TI  - Molecular flexibility of Mycobacterium tuberculosis ribosome recycling factor and
      its functional consequences: an exploration involving mutants.
AB  - Internal mobility of the two domain molecule of ribosome recycling factor (RRF)
      is known to be important for its action. Mycobacterium tuberculosis RRF does not
      complement E. coli for its deficiency of RRF (in the presence of E. coli EF-G
      alone). Crystal structure had revealed higher rigidity of the M. tuberculosis RRF
      due to the presence of additional salt bridges between domains. Two inter-domain
      salt bridges and one between the linker region and the domain containing C
      terminal residues were disrupted by appropriate mutations. Except for a C
      terminal deletion mutant, all mutants showed RRF activity in E. coli when M.
      tuberculosis EF-G was also co-expressed. The crystal structures of the point
      mutants, that of the C-terminal deletion mutant and that of the protein grown in
      the presence of a detergent, were determined. The increased mobility resulting
      from the disruption of the salt bridge involving the hinge region allows the
      appropriate mutant to weakly complement E. coli for its deficiency of RRF even in
      the absence of simultaneous expression of the mycobacterial EF-G. The loss of
      activity of the C-terminal deletion mutant appears to be partly due to the
      rigidification of the molecule consequent to changes in the hinge region.

PMID- 24296888
TI  - Realizing directional cloning using sticky ends produced by 3'-5' exonuclease of
      Klenow fragment.
AB  - The Klenow fragment (KF) has been used to make the blunt end as a tool enzyme.
      Its 5'-3' polymerase activity can extend the 5' overhanging sticky end to the
      blunt end, and 3'-5' exonuclease activity can cleave the 3' overhanging sticky
      end to the blunt end. The blunt end is useful for cloning. Here, we for the first
      time determined that a sticky end can be made by using the 3'-5' exonuclease
      activity of KF. We found that KF can cleave the blunt end into certain sticky
      ends under controlled conditions. We optimized enzyme cleavage conditions, and
      characterized the cleaved sticky ends to be mainly 2 nt 5' overhang. By using
      these sticky ends, we realized ligation reaction in vitro, and accomplished
      cloning short oligonucleotides directionally with high cloning efficiency. In
      some cases, this method can provide sticky end fragments in large scale for
      subsequent convenient cloning at low cost.

PMID- 24296889
TI  - alpha2,6 sialylation associated with increased beta 1,6-branched N
      oligosaccharides influences cellular adhesion and invasion.
AB  - Expression of beta1,6-branched N-linked oligosaccharides have a definite
      association with invasion and metastasis of cancer cells. However, the mechanism
      by which these oligosaccharides regulate these processes is not well understood.
      Invasive variants of B16 murine melanoma, B16F10 (parent) and B16BL6 (highly
      invasive variant) cell lines have been used for these studies. We demonstrate
      that substitution of alpha2,6-linked sialic acids on multiantennary structures
      formed as a result of beta1,6-branching modulate cellular adhesion on both
      extracellular matrix (ECM) and basement membrane (BM) components. Removal of
      alpha2,6 sialic acids either by enzymatic desialylation or by stably down
      regulating the ST6Gal-I (enzyme that catalyses the addition of alpha2,6-linked
      sialic acids on N-linked oligosaccharides) by lentiviral driven shRNA decreased
      the adhesion on both ECM and BM components and invasion through reconstituted BM
      matrigel.

PMID- 24296890
TI  - Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal
      death in rat brain after status epilepticus.
AB  - We sought to clarify the involvement and the intra-cerebral distribution
      variability of C/EBP homologous protein (CHOP), a representative molecule related
      to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in
      neuronal death resulting from status epilepticus in rats. The expression patterns
      of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were
      assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in
      the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double
      fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase
      mediated DNA nick-end labelling (TUNEL) method were performed to clarify the
      involvement of CHOP in cell death. SE resulted in a timedependent increase in the
      expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3,
      6 and 12 h after SE and no brain region variability was found. The expression of
      CHOP protein was also increased, reached its peak at 24 h and remained high at 48
      h. CHOP protein expression, however, showed brain region variability with highest
      expression noted in the hippocampus followed by the striatum, and lowest in the
      cortex. The up-regulation of CHOP occurring at the transcriptional level was
      demonstrated by real-time PCR. Double fluorescence showed that CHOP expression
      strongly correlated with neurons undergoing apoptosis. The results indicated that
      SE compromises the function of the ER and that the hippocampus is more vulnerable
      than the cortex and the striatum.

PMID- 24296891
TI  - Maternal hormonal interventions as a risk factor for Autism Spectrum Disorder: an
      epidemiological assessment from India.
AB  - Globalization and women empowerment have led to stressful life among Indian
      women. This stress impairs women's hormonal makeup and menstrual cycle, leading
      to infertility. National Family Health Survey-3 (NFHS-3) reports a decline in
      fertility status in India, indicating a rise in various infertility treatments
      involving hormonal interventions. No studies are available from India on the risk
      association link between maternal hormonal treatments and ASD. Hence, this study
      explores the association of maternal hormonal interventions with risk for ASD.
      Parents of 942 children (471 ASD and 471 controls) across 9 cities in India
      participated in the questionnaire-based study. The questionnaire was pilot tested
      and validated for its content and reliability as a psychometric instrument. Data
      collection was done at 70 centres through direct interaction with parents and
      with the help of trained staff. Statistical analysis of data was carried out
      using SAS 9.1.3. Out of the 471 ASD cases analysed, 58 mothers had undergone
      hormonal interventions (12.3 percent) while there were only 22 mothers among
      controls who underwent hormonal interventions (4.6 percent). According to
      logistic regression analysis maternal hormonal intervention (OR=2.24) was a
      significant risk factor for ASD.

PMID- 24296892
TI  - ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi
      population.
AB  - Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions
      between environmental factors and certain genetic factors. Genetic variants in
      the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been
      associated with abnormalities of serum lipid levels of high-density lipoprotein
      (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases,
      and this condition has been considered to be involved in the mechanism of insulin
      resistance (IR). Therefore, we investigated possible association between ABCA1
      C69T gene polymorphism and T2DMin a Saudi population. This study was carried out
      with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T
      polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment
      Length Polymorphism technique. We observed that the frequency of the T allele of
      the ABCA1 C69T gene was significantly higher in healthy subjects compared to
      T2DMpatients (0.28 vs 0.45; p less than 0.0001; OR (95 percent CI) = 0.4624
      (0.3732-0.5729), and therefore the T allele may be a protective factor against
      T2DM in the Saudi population.

PMID- 24296893
TI  - Signatures of positive selection in LY96 gene in vertebrates.
AB  - As a secreted glycoprotein that binds to the extracellular domain of Toll-like
      receptor 4 (TLR4), Lymphocyte Antigen 96 (LY96), also called myeloid
      differentiation 2 (MD2), is required for the activation of TLR4 by
      lipopolysaccharide (LPS) and plays an important role in innate immunity, which is
      the first line of defence against microbial infections. Previous studies have
      proposed that mammalian toll-like receptors (TLRs) have evolved under
      diversifying selection due to their role in pathogen detection. Given the fact
      that LY96 is highly functionally linked to TLR4, it would be interesting to test
      whether LY96 is under the intense pressure of natural selection. To investigate
      the natural selection hypothesis, we compared the coding sequences from 13
      vertebrates and evaluated the molecular evolution of LY96 gene in these species.
      Result shows that natural selection at exon 4 has indeed played a role in shaping
      the function of LY96 in the course of evolution. In addition to the study of
      Nakajima, we found the two branch nodes with Ka/Ks ratios greater than 1: the one
      leading to cow and pig and the other to rabbit and the primates.

PMID- 24296894
TI  - Assessment of lexical semantic judgment abilities in alcohol-dependent subjects:
      an fMRI study.
AB  - Neuropsychological studies have shown that alcohol dependence is associated with
      neurocognitive deficits in tasks requiring memory, perceptual motor skills,
      abstraction and problem solving, whereas language skills are relatively spared in
      alcoholics despite structural abnormalities in the language-related brain
      regions. To investigate the preserved mechanisms of language processing in
      alcohol-dependents, functional brain imaging was undertaken in healthy controls
      (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment
      task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took
      more time than controls for performing the task but there was no significant
      difference in their response accuracy. fMRI data analysis revealed that while
      performing the task, the alcoholics showed enhanced activations in left
      supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle
      temporal gyrus as compared to control subjects. The extensive activations
      observed in alcoholics as compared to controls suggest that alcoholics recruit
      additional brain areas to meet the behavioural demands for equivalent task
      performance. The results are consistent with previous fMRI studies suggesting
      compensatory mechanisms for the execution of task for showing an equivalent
      performance or decreased neural efficiency of relevant brain networks. However,
      on direct comparison of the two groups, the results did not survive correction
      for multiple comparisons; therefore, the present findings need further
      exploration.

PMID- 24296895
TI  - White Spot Syndrome Virus infection in Penaeus monodon is facilitated by
      housekeeping molecules.
AB  - White Spot Syndrome Virus (WSSV) is a major pathogen in shrimp aquaculture, and
      its rampant spread has resulted in great economic loss. Identification of host
      cellular proteins interacting with WSSV will help in unravelling the repertoire
      of host proteins involved in WSSV infection. In this study, we have employed one
      dimensional and two-dimension virus overlay protein binding assay (VOPBA)
      followed by matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) to identify the host proteins of Penaeus monodon that
      could interact with WSSV. The VOPBA results suggest that WSSV interacted with
      housekeeping proteins such as heat shock protein 70, ATP synthase subunit beta,
      phosphopyruvate hydratase, allergen Pen m 2, glyceraldehyde-3-phosphate
      dehydrogenase, sarcoplasmic calcium-binding protein, actin and 14-3-3-like
      protein. Our findings suggest that WSSV exploits an array of housekeeping
      proteins for its transmission and propagation in P. monodon.

PMID- 24296896
TI  - Biomineralization: Some complex crystallite-oriented skeletal structures.
AB  - The present review focuses on some specific aspects of biomineralization with
      regard to the evolution of the first focused visioning systems in trilobites, the
      formation of molluscan shell architecture, dental enamel and its biomechanical
      properties and the structure of the calcified amniote egg, both fossil and
      recent. As an interdisciplinary field, biomineralization deals with the
      formation, structure and mechanical strength of mineralized skeletonized tissue
      secreted by organisms. Mineral matter formed in this way occurs in all three
      domains of life and consists of several mineral varieties, of which carbonates,
      phosphates and opaline silica are the most common. Animals and plants need
      mechanical support to counteract gravitational forces on land and hydrostatic
      pressure in the deep ocean, which is provided by a skeletonized framework.
      Skeleton architecture mainly consists of basic elements represented by small
      usually micrometer- to nanometer-sized crystallites of calcite and aragonite for
      carbonate systems and apatite crystallites for phosphatic ones, and then these
      building blocks develop into structured more complex frameworks. As selective
      pressures work towards optimizing stress and response, the orientation,
      morphology and structural arrangement of the crystallites indicates the
      distribution of the stress field of the biomineralized tissue. Large animals such
      as the dinosaurs have to deal with large gravitational forces, but in much
      smaller skeletonized organism such as the coccoliths, a few micrometer in
      diameter made up of even smaller individual crystallites, van der Waals forces
      play an increasingly important role and are at present poorly understood.
      Skeleton formation is dependent upon many factors including ambient water
      chemistry, temperature and environment. Ocean chemistry has played a vital role
      in the origins of skeletonization, 500 to 600 million years (ma) ago with the
      dominance of calcium carbonate as the principal skeleton-forming tissue and with
      phosphates and silica as important but secondary materials. The preservation of
      calcareous skeletons in deep time has resulted in providing interesting
      information: for example, the number of days in the Devonian year has been
      established on the basis of well-preserved lunar (annual) cycles, and isotope
      chemistry has led to an elaborate protocol for using O18/O16 stable isotopes for
      palaeotemperature measurements in the geological past. Stable isotopes of dental
      apatite have helped to establish ecological shifts (terrestrial to wholly marine)
      during the evolution of the Cetacea. Biomineralization as a field of
      specialization is still searching for its own independent identity, but
      gradually, its importance is being realized as a model for engineering
      applications especially at the nanometer scale.

PMID- 24296898
TI  - Origin and occurrence of sexual and mating systems in Crustacea: a progression
      towards communal living and eusociality.
AB  - Crustaceans are known for their unrivalled diversity of sexual systems, as well
      as peculiar mating associations to achieve maximum mating success and
      fertilization accomplishment. Although sexes are separate in most species,
      various types of hermaphroditism characterize these predominantly aquatic
      arthropods. A low operational sex ratio between female and male, together with
      temporally limited receptivity of females towards males, imposes restrictions on
      the structuring of mating systems in crustaceans. The basic mating systems
      consist of monogamy, polygamy, mate guarding and pure searching. Understandably,
      ecological influences may also play a determinative role in the evolution of such
      sexual and mating systems in crustaceans. An important outcome of the crustacean
      sexual biology is the development of complex social structures in many aquatic
      species, in much the same way insects have established them in terrestrial
      conditions. In addition, groups like isopods and certain families of brachyuran
      crabs have shown terrestrial adaptation, exhibiting peculiar reproductive modes,
      sometimes reminiscent of their terrestrial counterparts, insects. Many caridean
      shrimps, living in symbiotic relationship with other marine invertebrates in the
      coral reef habitats, have reached pinnacle of complexity in sexuality and
      peculiar mating behaviours, resulting in communal living and establishing
      advanced social systems, such as eusociality.

PMID- 24296897
TI  - Side-effects of protein kinase inhibitors on ion channels.
AB  - Protein kinases are one of the largest gene families and have regulatory roles in
      all aspects of eukaryotic cell function. Modulation of protein kinase activity is
      a desirable therapeutic approach for a number of human diseases associated with
      aberrant kinase activity, including cancers, arthritis and cardiovascular
      disorders. Several strategies have been used to develop specific and selective
      protein kinase modulators, primarily via inhibition of phosphorylation and down
      regulation of kinase gene expression. These strategies are effective at
      regulating intracellular signalling pathways, but are unfortunately associated
      with several undesirable effects, particularly those that modulate ion channel
      function. In fact, the side-effects have precluded these inhibitors from being
      both useful experimental tools and therapeutically viable. This review focuses on
      the ion channel side-effects of several protein kinase inhibitors and
      specifically on those modulating K+, Na+ and Ca2+ ion channels. It is hoped that
      the information provided with a detailed summary in this review will assist the
      future development of novel specific and selective compounds targeting protein
      kinases both for experimental tools and for therapeutic approaches.

PMID- 24296900
TI  - Familial coaggregation of Alzheimer's disease and Parkinson's disease: systematic
      review and meta-analysis.
AB  - BACKGROUND: Familial aggregation has been shown for Alzheimer's disease (AD) and
      Parkinson's disease (PD) separately, and it has been hypothesized that these
      diseases also coaggregate in families. METHODS: The authors investigated familial
      coaggregation of AD and PD by conducting a systematic review and meta-analysis.
      PubMed was searched for relevant studies published through the end of October
      2012. Three independent investigators screened publications and extracted data.
      Relative risk estimates of AD risk associated with family history of PD or
      parkinsonism, or PD risk associated with family history of AD or dementia, were
      summarized into metaestimates using random effects models. Heterogeneity and
      publication bias were tested using Higgins' and Egger's tests, respectively.
      RESULTS: We included 16 studies in the review, with 14 included in any meta
      analysis. AD risk associated with family history of PD yielded a summary hazard
      ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a
      summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control
      studies. PD risk associated with family history of AD yielded a summary OR of
      0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant
      heterogeneity among studies, nor significant publication bias. CONCLUSIONS: There
      may be familial coaggregation of AD and PD, although the association was modest
      and only apparent when studying AD risk associated with family history of PD.

PMID- 24296899
TI  - Integrated genomics and molecular breeding approaches for dissecting the complex
      quantitative traits in crop plants.
AB  - The enormous population growth, climate change and global warming are now
      considered major threats to agriculture and world's food security. To improve the
      productivity and sustainability of agriculture, the development of highyielding
      and durable abiotic and biotic stress-tolerant cultivars and/climate resilient
      crops is essential. Henceforth, understanding the molecular mechanism and
      dissection of complex quantitative yield and stress tolerance traits is the prime
      objective in current agricultural biotechnology research. In recent years,
      tremendous progress has been made in plant genomics and molecular breeding
      research pertaining to conventional and next-generation whole genome,
      transcriptome and epigenome sequencing efforts, generation of huge genomic,
      transcriptomic and epigenomic resources and development of modern genomics
      assisted breeding approaches in diverse crop genotypes with contrasting yield and
      abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism
      and gene regulatory networks controlling such complex quantitative traits is not
      yet well understood in crop plants. Therefore, we propose an integrated
      strategies involving available enormous and diverse traditional and modern -omics
      (structural, functional, comparative and epigenomics) approaches/resources and
      genomics-assisted breeding methods which agricultural biotechnologist can
      adopt/utilize to dissect and decode the molecular and gene regulatory networks
      involved in the complex quantitative yield and stress tolerance traits in crop
      plants. This would provide clues and much needed inputs for rapid selection of
      novel functionally relevant molecular tags regulating such complex traits to
      expedite traditional and modern marker-assisted genetic enhancement studies in
      target crop species for developing high-yielding stress-tolerant varieties.

PMID- 24296901
TI  - Measuring single cell mass, volume, and density with dual suspended microchannel
      resonators.
AB  - Cell size, measured as either volume or mass, is a fundamental indicator of cell
      state. Far more tightly regulated than size is density, the ratio between mass
      and volume, which can be used to distinguish between cell populations even when
      volume and mass appear to remain constant. Here we expand upon a previous method
      for measuring cell density involving a suspended microchannel resonator (SMR). We
      introduce a new device, the dual SMR, as a high-precision instrument for
      measuring single-cell mass, volume, and density using two resonators connected by
      a serpentine fluidic channel. The dual SMR designs considered herein demonstrate
      the critical role of channel geometry in ensuring proper mixing and damping of
      pressure fluctuations in microfluidic systems designed for precision measurement.
      We use the dual SMR to compare the physical properties of two well-known cancer
      cell lines: human lung cancer cell H1650 and mouse lymphoblastic leukemia cell
      line L1210. 

PMID- 24296902
TI  - Effect of bosentan on pulmonary hypertension secondary to systolic heart failure.
AB  - OBJECTIVES: The dual endothelin receptor antagonist bosentan improves pulmonary
      vascular resistance (PVR) in patients with primary pulmonary hypertension (PH).
      The effects of bosentan on secondary PH due to systolic heart failure (HF) are
      not well defined. This study evaluates the effect and tolerability of bosentan in
      patients with PH secondary to HF. METHODS: Seventeen adult HF patients with PH
      and New York Heart Association class III-IV symptoms were treated with bosentan,
      62.5 mg twice daily, for 1 month, which was gradually increased to 125 mg twice
      daily thereafter. Right heart catheterization (RHC), a clinical evaluation and
      echocardiographic measurements were performed at baseline and at 4 +/- 3 (mean +/
      SD) months of follow-up. Response to bosentan was defined as an improvement in
      clinical, echocardiographic and RHC parameters. RESULTS: Six patients did not
      complete the study (therapy was discontinued due to hypotension, elevated liver
      enzymes or acute decompensation of HF), 11 patients completed the follow-up; 9
      patients responded to therapy. Systemic arterial pressures, pulmonary pressures,
      PVR and the transpulmonary gradient significantly decreased compared with
      baseline levels in 9 responders (p = 0.05, 0.05, 0.01 and 0.004, respectively),
      and 4 became eligible for heart transplantation and 3 for left ventricular assist
      device implantation. CONCLUSIONS: Bosentan decreased pulmonary pressures and PVR
      in the majority of patients with PH secondary to systolic HF, thereby allowing
      them to be considered candidates for heart transplantation.

PMID- 24296903
TI  - Host-guest recognition-induced color change of water-soluble pillar[5]arene
      modified silver nanoparticles for visual detection of spermine analogues.
AB  - Silver nanoparticles with narrow size distribution were prepared in the presence
      of a water-soluble pillar[5]arene. They could be used for visual detection of
      spermine analogues in water through host-guest interactions. 

PMID- 24296904
TI  - Effects of home visits by paraprofessionals and by nurses on children: follow-up
      of a randomized trial at ages 6 and 9 years.
AB  - IMPORTANCE: The Nurse-Family Partnership delivered by nurses has been found to
      produce long-term effects on maternal and child health in replicated randomized
      trials. A persistent question is whether paraprofessional home visitors might
      produce comparable effects. OBJECTIVE: To examine the impact of prenatal and
      infancy/toddler home visits by paraprofessionals and by nurses on child
      development at child ages 6 and 9 years. DESIGN, SETTING, AND PARTICIPANTS:
      Randomized trial in public and private care settings in Denver, Colorado, of 735
      low-income women and their first-born children (85% of the mothers were
      unmarried; 47% were Hispanic, 35% were non-Hispanic white, 15% were African
      American, and 3% were American Indian/Asian). INTERVENTIONS: Home visits provided
      from pregnancy through child age 2 years delivered in one group by
      paraprofessionals and in the other by nurses. MAIN OUTCOMES AND MEASURES: Reports
      of children's internalizing, externalizing, and total emotional/behavioral
      problems, and tests of children's language, intelligence, attention, attention
      dysfunction, visual attention/task switching, working memory, and academic
      achievement. We hypothesized that program effects on cognitive-related outcomes
      would be more pronounced among children born to mothers with low psychological
      resources. We report paraprofessional-control and nurse-control differences with
      P < .10 given similar effects in a previous trial, earlier effects in this trial,
      and limited statistical power. RESULTS: There were no significant
      paraprofessional effects on emotional/behavioral problems, but paraprofessional
      visited children born to mothers with low psychological resources compared with
      control group counterparts exhibited fewer errors in visual attention/task
      switching at age 9 years (effect size = -0.30, P = .08). There were no
      statistically significant paraprofessional effects on other primary outcomes.
      Nurse-visited children were less likely to be classified as having total
      emotional/behavioral problems at age 6 years (relative risk [RR] = 0.45, P =
      .08), internalizing problems at age 9 years (RR = 0.44, P = .08), and
      dysfunctional attention at age 9 years (RR = 0.34, P = .07). Nurse-visited
      children born to low-resource mothers compared with control-group counterparts
      had better receptive language averaged over ages 2, 4, and 6 years (effect size =
      0.30, P = .01) and sustained attention averaged over ages 4, 6, and 9 years
      (effect size = 0.36, P = .006). There were no significant nurse effects on
      externalizing problems, intellectual functioning, and academic achievement.
      CONCLUSIONS AND RELEVANCE: Children born to low-resource mothers visited by
      paraprofessionals exhibited improvement in visual attention/task switching. Nurse
      visited children showed improved behavioral functioning, and those born to low
      resource mothers benefited in language and attention but did not improve in
      intellectual functioning and academic achievement. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00438282 and NCT00438594.

PMID- 24296905
TI  - Combining next-generation sequencing and online databases for microsatellite
      development in non-model organisms.
AB  - Next-generation sequencing (NGS) is revolutionising marker development and the
      rapidly increasing amount of transcriptomes published across a wide variety of
      taxa is providing valuable sequence databases for the identification of genetic
      markers without the need to generate new sequences. Microsatellites are still the
      most important source of polymorphic markers in ecology and evolution. Motivated
      by our long-term interest in the adaptive radiation of a non-model species
      complex of whitefishes (Coregonus spp.), in this study, we focus on
      microsatellite characterisation and multiplex optimisation using transcriptome
      sequences generated by Illumina(r) and Roche-454, as well as online databases of
      Expressed Sequence Tags (EST) for the study of whitefish evolution and
      demographic history. We identified and optimised 40 polymorphic loci in multiplex
      PCR reactions and validated the robustness of our analyses by testing several
      population genetics and phylogeographic predictions using 494 fish from five
      lakes and 2 distinct ecotypes. 

PMID- 24296906
TI  - Genetic polymorphisms in calcitonin receptor gene and risk for recurrent kidney
      calcium stone disease.
AB  - INTRODUCTION: In this study the full sequence of the calcitonin receptor gene
      (CALCR) in a group of Iranian males suffering from recurrent calcium urinary
      stones was compared with that of a control group. METHODS: Serum and urinary
      biochemistry related to urolithiasis were evaluated in 105 males diagnosed with
      recurrent kidney calcium stones and 101 age-matched healthy control males. The
      polymerase chain reaction single-strand conformation polymorphism method was used
      to detect new polymorphisms in the CALCR. RESULTS: Nine polymorphisms were
      detected; seven were in the non-coding and two in the coding region. The T allele
      associated with the 3'UTR+18C>T polymorphism was observed exclusively in the
      stone formers. The exact odds ratio for the T allele in this locus for those at
      risk of stone formation was 36.72 (95% CI 4.95-272.0) (p < 0.001). The mean
      (standard deviation) urine calcium concentration was 117 (60) mg/l in patients
      with the C allele and 152 (72) mg/l in those with the T allele (p = 0.03). In
      addition, IVS1-6T>C and IVS1insA polymorphisms in intron 1 were associated with
      kidney stone disease (p < 0.001). Regarding single nucleotide polymorphism 447,
      mean (standard deviation) of serum calcitonin levels were 16.7 (18.7) pg/ml, 10.5
      (11.0) pg/ml and 9.94 (9.7) pg/ml in subjects with TT, TC and CC genotypes,
      respectively (p = 0.01). CONCLUSION: Our data indicate a potential association
      between 3'UTR+18C>T and intron 1 polymorphisms in the CALCR and the risk of
      kidney stone disease.

PMID- 24296907
TI  - Diagnosis code assignment: models and evaluation metrics.
AB  - BACKGROUND AND OBJECTIVE: The volume of healthcare data is growing rapidly with
      the adoption of health information technology. We focus on automated ICD9 code
      assignment from discharge summary content and methods for evaluating such
      assignments. METHODS: We study ICD9 diagnosis codes and discharge summaries from
      the publicly available Multiparameter Intelligent Monitoring in Intensive Care II
      (MIMIC II) repository. We experiment with two coding approaches: one that treats
      each ICD9 code independently of each other (flat classifier), and one that
      leverages the hierarchical nature of ICD9 codes into its modeling (hierarchy
      based classifier). We propose novel evaluation metrics, which reflect the
      distances among gold-standard and predicted codes and their locations in the ICD9
      tree. Experimental setup, code for modeling, and evaluation scripts are made
      available to the research community. RESULTS: The hierarchy-based classifier
      outperforms the flat classifier with F-measures of 39.5% and 27.6%, respectively,
      when trained on 20,533 documents and tested on 2282 documents. While recall is
      improved at the expense of precision, our novel evaluation metrics show a more
      refined assessment: for instance, the hierarchy-based classifier identifies the
      correct sub-tree of gold-standard codes more often than the flat classifier.
      Error analysis reveals that gold-standard codes are not perfect, and as such the
      recall and precision are likely underestimated. CONCLUSIONS: Hierarchy-based
      classification yields better ICD9 coding than flat classification for MIMIC
      patients. Automated ICD9 coding is an example of a task for which data and tools
      can be shared and for which the research community can work together to build on
      shared models and advance the state of the art.

PMID- 24296909
TI  - Chronic pain in the newborn: toward a definition.
AB  - OBJECTIVE: Chronic pain is poorly addressed in neonatal pain research. We aimed
      at contributing to define the concept of chronic pain in the newborn. METHOD: We
      designed a Web-based, 3-round Delphi survey. We invited an international panel of
      experts (health care providers and parents) in the fields of neonatology and
      neonatal pain to participate. RESULTS: In the first round, participants (n=189)
      answered 3 open-ended questions: (1) define chronic pain in your own words, (2)
      what are the possible causes, and (3) which signs and symptoms are used to
      diagnose chronic pain? The answers were categorized and summarized into 437
      statements, which were valued by the participants (n=189) on a 5-point Likert
      scale. In the second round, the remaining participants (n=72) were asked to
      reflect on 65 selected statements with a mode or median >=4 or mean >=3.75. These
      threshold values provided the opportunity to reach consensus in the following
      round. In the third round, the remaining participants (n=33) were provided with
      the group and individual responses. This process resulted in 23 statements with
      mode, mean, and median of >=4, on which the participants reached consensus.
      DISCUSSION: Although several etiologic factors were defined, no useful diagnostic
      criterion could be identified. The survey resulted in a description of chronic
      pain in the newborn. Identifying chronic pain is clinically relevant because it
      interferes with growth, prolongs hospitalization, leads to altered pain
      perception, and impairs cognitive and behavioral development.

PMID- 24296908
TI  - N-CANDA data integration: anatomy of an asynchronous infrastructure for multi
      site, multi-instrument longitudinal data capture.
AB  - The infrastructure for data collection implemented by the National Consortium on
      Alcohol and NeuroDevelopment in Adolescence (N-CANDA) for data collection
      comprises several innovative features: (a) secure, asynchronous transfer and
      persistent storage of collected data via a revision control system; (b) two-stage
      import into a longitudinal database; and (c) use of a script-controlled web
      browser for data retrieval from a third-party, web-based neuropsychological test
      battery. The asynchronous operation of data transmission and import is of
      particular benefit, as it has allowed the consortium sites to begin data
      collection before the receiving database infrastructure had been deployed.
      Records were collected within 86 days of funding, 35 days after finalizing the
      collected instruments. Final instruments were added to the database import 225
      days after instrument selection, with up to 173 records already collected at that
      time. Thus, the concepts implemented in N-CANDA's data collection system helped
      reduce project start-up time by several months. 

PMID- 24296910
TI  - Effectiveness of duloxetine compared with pregabalin and gabapentin in diabetic
      peripheral neuropathic pain: results from a German observational study.
AB  - OBJECTIVES: This study aimed to compare the effectiveness of duloxetine (DLX) and
      the anticonvulsants pregabalin (PGB) and gabapentin (GBP) for the treatment of
      diabetic peripheral neuropathic pain (DPNP) in routine clinical care. MATERIALS
      AND METHODS: Data from a 6-month, noninterventional study involving 2575 patients
      in whom treatment of DPNP was initiated with or changed to DLX, PGB, or GBP
      (n=1523) were analyzed post hoc; patients treated with other medications or
      combinations were excluded from this analysis. Propensity scoring was used to
      compare patient groups, assessing Brief Pain Inventory (BPI), Clinical and
      Patient Global Impression (CGI/PGI), the Hospital Anxiety and Depression Scale
      (HADS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF
      12). RESULTS: Mean median daily dosage over 6 months was 53.9 mg for DLX (N=931),
      173.5 mg for PGB (N=248), and 727.8 mg for GBP (N=351). BPI average pain severity
      (last observation carried forward, mean [SD]) decreased by 2.3 [2.30] points for
      DLX patients, and by 1.9 [2.22] in PGB, and 1.1 [2.15] in GBP patients. This
      difference remained statistically significant (DLX vs. PGB: P=0.029; DLX vs. GBP:
      P<0.001) after adjustment by propensity scores. Similar findings were also seen
      for the BPI interference score, CGI and PGI, the HADS anxiety score, the HADS
      depression score. DISCUSSION: When compared with DLX, the low doses of PGB and
      GBP used in this noninterventional study might have contributed to the lower
      effectiveness found for both anticonvulsants in the treatment of patients with
      DPNP.

PMID- 24296911
TI  - Sex-determining mechanisms in insects based on imprinting and elimination of
      chromosomes.
AB  - As a rule, the sex of an individual is fixed at fertilization, and the
      chromosomal constitution of the zygote is a direct consequence of the chromosomal
      constitution of the gametes. However, there are cases in which the chromosomal
      differences determining sex are brought about by elimination or inactivation of
      chromosomes in the embryo. In Sciaridae insects, all zygotes start with the XXX
      constitution; the loss of either 1 or 2 X chromosomes determines whether the
      zygote becomes XX (female) or X0 (male). In Cecydomyiidae and Collembola insects,
      all zygotes start with the XXXX constitution. If the embryo does not eliminate
      any X chromosome, this remains XXXX and develops as female, whereas if 2 X
      chromosomes are eliminated, the embryo becomes XX0 and develops as a male. In the
      coccids (scale insects), the chromosomal differences between the sexes result
      from either the elimination or the heterochromatinization (inactivation) of half
      of the chromosomes giving rise to haploid males and diploid females. The
      chromosomes that are eliminated or inactivated are those inherited from the
      father. Therefore, in the formation of the sex-determining chromosomal signal in
      those insects, a marking ('imprinting') process must occur in one of the parents,
      which determines that the chromosomes to be eliminated or inactivated are of
      paternal origin. In this article, the sex determination mechanism of these
      insects and the associated imprinting process are reviewed.

PMID- 24296912
TI  - Investigation of nanolevel molecular packing and its role in thermo-mechanical
      properties of PVA-fMWCNT composites: positron annihilation and small angle X-ray
      scattering studies.
AB  - Carbon based nanofillers have shown phenomenal improvements in thermo-mechanical
      properties of poly vinyl alcohol (PVA) based nanocomposites depending on their
      interaction with PVA molecules and dispersion in the polymer matrix. In the
      present study, PVA based nanocomposites with amino-functionalized multi-wall
      carbon nanotubes (fMWCNTs, 0.2, 0.4, 0.8 and 1.0 wt%) were prepared by a simple
      casting method from aqueous solution. The relative increase in Young's modulus
      with 0.4% fMWCNTs was observed to be comparable with that for PVA-nanodiamond
      composite films which have been shown to have higher strength compared to
      nanotube and graphene oxide based nanocomposites. In order to investigate the
      nanolevel molecular packing (sub-nano level free volumes and nano level lamellar
      structure) and its role in thermal and mechanical properties, positron
      annihilation spectroscopy and small angle scattering have been used. The
      crystallinity and morphology of the samples were characterized using X-ray
      diffraction and scanning electron microscopy. The studies showed that interfacial
      interaction between PVA molecules and functionalities on the surface of fMWCNTs
      results in the formation of an ordered structure of PVA molecules which enhances
      load transfer between the PVA matrix and fMWCNTs leading to improved mechanical
      properties. The thermal properties of the composites were observed to be
      unaffected at the studied filler concentration. 

PMID- 24296914
TI  - The non-neuronal cholinergic system in health and disease.
AB  - Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule
      that can be released by and act on non-neuronal cells. In these cells the system
      of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is
      termed the non-neuronal cholinergic system (NNCS). There is increasing evidence
      that the NNCS is dysregulated in various diseases and can have an influence on
      their pathology. However, for many organ systems not much is known about the
      expression and function of the NNCS. Thus, this review focusses on the role of
      the NNCS in different organ systems in health and disease. Dysregulation of ACh
      synthesis and release, mutations or polymorphisms in genes encoding NNCS
      components, and auto-antibodies against NNCS components are common factors
      influencing disease progression. Pharmacological agents targeting the NNCS are
      already successfully in clinical use for some disorders, indicating that
      interfering with this system is very promising and more research is needed to
      elucidate the role of the NNCS in different tissues and pathological states.

PMID- 24296915
TI  - Binding-induced autonomous disassembly of aptamer-DNAzyme supersandwich
      nanostructures for sensitive electrochemiluminescence turn-on detection of
      ochratoxin A.
AB  - The self-assembled DNA nanostructure has been one of the most interesting
      research areas in the field of nanoscience, and the application of the DNA self
      assembled nanostructures in biosensing is still in the early stage. In this work,
      based on the target-induced autonomous disassembly of the aptamer-DNAzyme
      supersandwich nanostructures, we demonstrated a highly sensitive strategy for
      electrochemiluminescent (ECL) detection of ochratoxin A (OTA). The aptamer
      DNAzyme supersandwich nanostructures, which exhibited significant ECL quenching
      effect toward the oxygen/persulfate (O2/S2O8(2-)) system, were self-assembled on
      the gold electrode surface. The presence of the target OTA and the exonuclease
      (RecJf) resulted in autonomous disassembly of the nanostructures and cyclic reuse
      of OTA, leading to efficient recovery of the ECL emission and highly sensitive
      detection of OTA. Our developed method also showed high selectivity against other
      interference molecules and can be applied for the detection of OTA in real red
      wine samples, which offers the proposed method opportunities for designing new
      DNA-based nanostructures for biosensing applications. 

PMID- 24296917
TI  - Healthcare: too much of a good thing?

PMID- 24296916
TI  - A low pH sensor from an esterified pillar[5]arene.
AB  - An esterified pillar[5]arene has been incorporated into a PVC electrochemical
      membrane. The resulting pH-responsive sensor functions in the range of pH 1 to 4
      in a non-linear manner. 

PMID- 24296918
TI  - Mono-limb ataxia caused by motor cortical infarction: case report and review of
      the literature.

PMID- 24296920
TI  - Probiotics and Necrotising Enterocolitis: the devil (as always) is in the detail.
      Commentary on N. Ofek Shlomai et al.: Probiotics for preterm neonates: what will
      it take to change clinical practice? (Neonatology 2014;105:64-70).

PMID- 24296921
TI  - Psychopathology and its risk and protective factors in hearing-impaired children
      and adolescents: a systematic review.
AB  - IMPORTANCE: Pediatric hearing impairment is a chronic handicap that can
      potentially lead to the development of psychopathology. Yet, for hearing-impaired
      children and adolescents, the exact occurrence of various forms of
      psychopathology and its causes are unclear, while this knowledge is essential to
      enable targeted screenings and interventions. OBJECTIVE: To investigate the level
      of psychopathological symptoms in hearing-impaired children and adolescents as
      compared with normally hearing peers. Second, the influence of type of hearing
      device and possible risk and protective factors on psychopathology were examined.
      EVIDENCE REVIEW: A systematic literature search was performed covering relevant
      databases, including PubMed, Embase, and Web of Science. Two independent
      researchers identified the relevant articles. The final search was performed on
      May 2, 2013, and resulted in a total of 35 articles. FINDINGS: Literature
      consistently demonstrated that hearing-impaired children and adolescents were
      more prone to developing depression, aggression, oppositional defiant disorder,
      conduct disorder, and psychopathy than their normally hearing peers. Levels of
      anxiety, somatization, and delinquency were elevated in some, but not all,
      hearing-impaired participants, for reasons related to sex, age, and type of
      school. Divergent results were obtained for the level of attention
      deficit/hyperactivity disorder and the influence of type of hearing device on
      psychopathology. Possible risk and protective factors were identified, including
      age at detection and intervention of hearing loss, additional disabilities,
      communication skills, intelligence, type of school, and number of siblings.
      CONCLUSIONS AND RELEVANCE: Literature on psychopathology in hearing-impaired
      children and adolescents is scarce and sometimes inconsistent. To define a more
      precise occurrence of psychopathology, more studies are needed. These studies
      should have a longitudinal design to draw firmer conclusions on causality.
      Hopefully, this will lead to more knowledge in the future to help and support
      each hearing-impaired individual.

PMID- 24296922
TI  - Transitions.

PMID- 24296923
TI  - Commentary: effect of obesity on mortality: comment on article by Banack and
      Kaufman.

PMID- 24296924
TI  - Commentary: selection bias as an explanation for the obesity paradox: just
      because it's possible doesn't mean it's plausible.

PMID- 24296925
TI  - Perhaps the correct answer is: (D) all of the above.

PMID- 24296926
TI  - Commentary: mobile phones and cancer: next steps after the 2011 IARC review.

PMID- 24296927
TI  - Commentary: extending organizational schema for causal effects.

PMID- 24296928
TI  - A conversation with Jean Golding.

PMID- 24296929
TI  - Gestational diabetes and the risk of cryptorchidism and hypospadias.

PMID- 24296930
TI  - Prenatal lead exposure and puberty timing in girls.

PMID- 24296931
TI  - Human papillomavirus vaccine in patients with systemic lupus erythematosus.

PMID- 24296932
TI  - Mortality risk of obesity and underweight is overestimated with self-reported
      body mass index.

PMID- 24296933
TI  - Number allowed to diagnose.

PMID- 24296934
TI  - Residential air pollution and lung cancer.

PMID- 24296935
TI  - Residential air pollution and lung cancer.

PMID- 24296936
TI  - Nonmalignant respiratory disease mortality in styrene-exposed workers.

PMID- 24296937
TI  - Nonmalignant respiratory disease mortality in styrene-exposed workers.

PMID- 24296938
TI  - Estimating causal effect with RCTs.

PMID- 24296939
TI  - Estimating causal effect with RCTs.

PMID- 24296940
TI  - Enhanced oxidative stability of non-Grignard magnesium electrolytes through
      ligand modification.
AB  - A series of non-Grignard Mg-electrolytes with various para-substituents was
      synthesized starting from commercially-available phenols. More electron
      withdrawing substituents shift the anodic stability of the electrolyte by 400 mV.
      The p-CF3 substituted phenol exhibits the highest stability of 2.9 V vs.
      Mg(2+/0), and cycles reversibly with the Chevrel-phase Mo6S8 Mg-ion cathode. 

PMID- 24296941
TI  - Electrochemical artifacts originating from nanoparticle contamination by Ag/AgCl
      quasi-reference electrodes.
AB  - Electrochemical techniques rely on the stability of a defined reference
      potential. Due to the need for miniaturization, electrochemical lab-on-a-chip
      platforms often employ Ag/AgCl quasi-reference electrodes for this purpose. Here,
      we report on electrochemical artifacts resulting from nanoparticle-electrode
      collisions originating from standard chlorinated silver wires. 

PMID- 24296942
TI  - Multiple virtual tunneling of Dirac fermions in granular graphene.
AB  - Graphene charge carriers behave as massless Dirac fermions, opening the exciting
      possibility to observe long-range virtual tunneling of electrons in a solid. In
      granular metals, electron hops arising from series of virtual transitions are
      predicted to yield observable currents at low-enough temperatures, but to date
      experimental evidence is lacking. We report on electron transport in granular
      graphene films self-assembled by hydrogenation of suspended graphene. While the
      log-conductance shows a characteristic T(-1/2) temperature dependence, cooling
      the samples below 10 K drives a triple crossover: a slope break in log
      conductance, simultaneous to a substantial increase in magneto-conductance and
      onset of large mesoscopic conductance fluctuations. These phenomena are
      signatures of virtual transitions of electrons between distant localized states,
      and conductance statistics reveal that the high crossover-temperature is due to
      the Dirac nature of granular graphene charge carriers. 

PMID- 24296943
TI  - Seminal vesicle invasion: accuracy and analysis of infiltration patterns with
      high-spatial resolution T2-weighted sequences on endorectal magnetic resonance
      imaging.
AB  - OBJECTIVE: To evaluate the accuracy of high-spatial resolution T2-weighted
      endorectal magnetic resonance imaging (eMRI) for detection and pattern depiction
      of seminal vesicle invasion (SVI) in patients with prostate cancer (PCa).
      METHODS: 376 patients were included who underwent eMRI for staging before radical
      open prostatectomy at 1.5 T with an endorectal coil. Statistical accuracy for
      detection of SVI was calculated. MR images of patients with SVI were further
      evaluated by two radiologists according to the classification by Wheeler and
      Ohori. RESULTS: In the cohort, 35 patients had SVI after histopathological
      evaluation of the prostatectomy specimen (stage pT3b). Sensitivity and
      specificity for detection of SVI were 48.6 and 97.7%, respectively. Negative and
      positive predictive values and overall accuracy were 94.9, 68.0, and 93.1%,
      respectively. Infiltration pattern analysis showed that type I invasion was most
      common with 48.6 followed by type IIa (31.4%) and IIb (20%). Type III was not
      present. There was no statistical significant difference between the three groups
      regarding Gleason score, age, and prostate-specific antigen level. CONCLUSIONS:
      eMRI with high-spatial resolution T2-weighted imaging is accurate for assessment
      of SVI. Depiction of different infiltration types of SVI is feasible. By adding
      information about the extent of SVI, diagnostic reporting and risk stratification
      could be improved.

PMID- 24296946
TI  - The effect of rate reduction on signaling prosodic contrasts in dysarthria.
AB  - BACKGROUND/AIMS: To understand how reducing speaking rate alters prosodic
      contrasts in speakers with dysarthria (DYS) and healthy controls (HC). METHODS:
      Seven male speakers with DYS (mean age = 34.9) and 7 age- and sex-matched HC
      (mean age = 36.9) produced identical phrases with affirmative (A), contrastive
      stress (CS) or question (Q) intonation at habitual and slow rate within a
      naturalistic game. Relative (word-to-word) changes in peak fundamental frequency
      (F0), intensity, and duration were compared across conditions, groups, and rates.
      RESULTS: For some contrasts, rate reduction differentially affected the speaking
      groups, with HC exaggerating and speakers with DYS dampening some prosodic cues.
      Rate reduction diminished the Q contrast for both groups, with reduced peak F0
      differences for HC and reduced word duration differences for HC and with DYS
      speakers. Slow rate also resulted in decreased lengthening of the final word for
      all three contrasts, thereby diminishing the Q contrast while exaggerating the CS
      and A contrasts. CONCLUSION: Although slow rate may improve segmental
      intelligibility, it may inadvertently dampen prosodic contrasts for some DYS
      speakers, thereby impacting communication effectiveness and naturalness.
      Implications for designing interventions that balance trade-offs between prosodic
      modulation and segmental clarity are discussed.

PMID- 24296947
TI  - Role of endobronchial and endoscopic ultrasound in pulmonary medicine.
AB  - In the last decade, endobronchial ultrasound (EBUS) has evolved into an important
      tool for diagnostic bronchoscopy in daily practice. EBUS has established as a
      standard for the diagnosis of hilar or mediastinal lymphadenopathy, as a guidance
      technique for peripheral pulmonary lesions and for the evaluation of tumor
      involvement of the tracheobronchial wall or mediastinum. In the meantime, EBUS
      has also taken a significant role in mediastinal staging in lung cancer patients.
      However, EBUS plays not only a role in the diagnosis of malignancies, it is also
      important for the diagnosis of benign disorders.

PMID- 24296945
TI  - Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in
      genes involved in marginal zone differentiation.
AB  - Splenic marginal zone lymphoma (SMZL) is a B-cell neoplasm whose molecular
      pathogenesis remains fundamentally unexplained, requiring more precise diagnostic
      markers. Previous molecular studies have revealed 7q loss and mutations of
      nuclear factor kappaB (NF-kappaB), B-cell receptor (BCR) and Notch signalling
      genes. We performed whole-exome sequencing in a series of SMZL cases. Results
      confirmed that SMZL is an entity distinct from other low-grade B-cell lymphomas,
      and identified mutations in multiple genes involved in marginal zone development,
      and others involved in NF-kappaB, BCR, chromatin remodelling and the
      cytoskeleton. 

PMID- 24296949
TI  - Quantum wells formed in transition-metal dichalcogenide nanosheet-superlattices:
      stability and electronic structures from first principles.
AB  - The possibility of forming quantum wells (QWs) in transition-metal dichalcogenide
      nanosheet assembled superlattices (SLs) was investigated by using the first
      principles calculations. The interfacial binding energies and electronic
      structures of MoS2/MX2 (MX2 = MoSe2, WS2, and WSe2) SLs were calculated. The
      interfacial binding energies show that all the SLs are stable, and the most
      stable atomic configuration is that where M atoms are located right above S
      atoms. By calculating the band offsets in the SLs, it was found that a QW with a
      depth of 0.17 eV can be formed in the MoS2 layer in MoS2/WSe2 SLs. The calculated
      band structure shows that this SL has an indirect band gap due to the tensile
      strained state of the MoS2 layer. The charge transfer between the two layers is
      very small, which is in favor of the QWs' formation. In particular, the depth of
      the QW in the SLs can be adjusted by strain engineering, which can be attributed
      to the different strain dependencies of the two materials' band gaps. These
      findings will guide the choice of future nanosheet assembled SLs to work on and
      suggest a new route to facilitate the design of QW based optoelectronic devices. 

PMID- 24296950
TI  - Protective effects of cariporide on endothelial dysfunction induced by
      homocysteine.
AB  - AIMS: Recent studies have reported that intracellular calcium (Ca(2+))
      mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction
      and the Na(+)/H(+) exchanger (NHE) is responsible for an increase in the
      intracellular Ca(2+) concentration in cardiovascular disease. We hypothesized
      that inhibition of the NHE had protective effects on Hcy-induced endothelial
      dysfunction. METHODS: Acetylcholine-induced endothelium-dependent relaxation
      (EDR) and biochemical parameters were measured in the rat isolated aorta. The
      level of reactive oxygen species (ROS) was designed by a specific fluorescent
      probe. The phosphorylation of the nuclear factor-kappaB (NF-kappaB) system was
      studied by Western blot. RESULTS: Cariporide significantly prevented Hcy-impaired
      EDR and increased nitric oxide (NO) release; endothelial NO synthase activity
      simultaneously decreased ROS production. We also found that cariporide blocked
      Hcy-induced NF-kappaB activation and inhibitor-kappaB degradation, thus
      inhibiting the production of tumor necrosis factor-alpha and intercellular
      adhesion molecule-1. CONCLUSIONS: The mechanisms of protective effects of
      cariporide may be related to the inhibition of NHE and the decrease in oxidative
      stress and inflammatory injury.

PMID- 24296951
TI  - Design of an environmentally sensitive fluorescent 8-aza-7-deaza-2'
      deoxyadenosine derivative with dual fluorescence for the specific detection of
      thymine.
AB  - A novel environmentally sensitive fluorescent (ESF) purine nucleoside, (cna)A,
      was synthesized and its photophysical properties were investigated. The base
      modified fluorescent nucleoside (cna)A exhibited remarkable solvatochromicity and
      environmentally sensitive dual fluorescence. By using (cna)A, we have developed
      highly thymine (T) selective fluorescent DNA probes that can sense the
      corresponding T in a target DNA/RNA sequence, as measured by a distinct change in
      emission wavelength.

PMID- 24296952
TI  - Special section guest editorial: optical imaging, sensing, and light interactions
      in cells and tissues.

PMID- 24296953
TI  - Corneal impairment in a patient with type 2 distal arthrogryposis.
AB  - OBJECTIVE: Case report of a 7-year-old male patient, diagnosed with idiopathic
      progressive corneal alteration developed within a period of 6 months. METHODS:
      Description of type 2 distal arthrogryposis affecting hands and feet, a
      bilateral, congenital hearing loss, alterations such as keloid-like scarring,
      congenital heart disease, and cryptorchidism with no relevant family history.
      RESULTS: Corrected visual acuity in the right eye (RE) was 0.5 and in the left
      eye was 1 and, in addition to that, a bilateral corneal subepithelial fibrosis
      that was denser in the RE without neovessels and no signs of inflammatory
      activity. CONCLUSION: This is the first publication relating arthrogryposis with
      corneal affectation, probably because of a collagen anomaly characteristic in
      these patients.

PMID- 24296954
TI  - Deep anterior lamellar keratoplasty for acanthamoeba keratitis complicating the
      use of Boston scleral lens.
AB  - BACKGROUND: This is the first reported case of Acanthamoeba keratitis (AK) in a
      Boston scleral lens user. Consequently, the risk factors and treatment for AK
      need to be addressed in this unique case. METHODS: We conducted a retrospective
      case study of a 45-year-old man using Boston scleral lens diagnosed with AK. Risk
      factors for infection and management of the condition were assessed. RESULTS:
      This 45-year old Boston scleral lens user's risk factors for developing AK
      included dry eye syndrome, autologous serum tear use, potential tap water
      exposure, and long-term systemic corticosteroid use. His infection was refractory
      to medical management and required deep anterior lamellar keratoplasty for
      curative treatment. CONCLUSION: Ophthalmologists should have a higher level of
      suspicion for AK in all scleral lens users and consider the use of deep anterior
      lamellar keratoplasty for refractory cases.

PMID- 24296955
TI  - Recurrent ocular surface inflammation associated with human herpesvirus 6
      infection.
AB  - OBJECTIVES: To report a case of atypical herpes keratitis and bilateral
      conjunctivitis associated with human herpesvirus 6 (HHV-6). METHODS: An
      immunocompetent 34-year-old man was referred for herpetic epithelial keratitis in
      his left eye, which was non-responsive to topical acyclovir. Biomicroscopy
      revealed a central dendritic ulcer with a white stromal infiltrate beneath the
      ulcer. RESULTS: The corneal scraping multiplex polymerase chain reaction (CLART
      ENTHERPEX, Genomica, Spain) was positive for HHV-6 and negative for herpes
      simplex virus, varicella zoster virus, cytomegalovirus, and Epstein-Barr virus.
      An improvement of the keratitis and visual acuity was achieved with topical
      fluorometholone and systemic valacyclovir. One year later, the patient complained
      of redness of the eyes. A slit-lamp examination disclosed bilateral follicular
      conjunctivitis, and HHV-6 DNA was once again detected in a conjunctival scraping
      of both eyes. CONCLUSIONS: Human herpesvirus 6 may be another causative agent for
      corneal ulcers and conjunctivitis in isolation. Stromal necrosis is a rare
      manifestation of herpetic dendritic keratitis. In these cases, we should consider
      the presence of HHV-6 in the differential diagnosis, even in immunocompetent
      patients.

PMID- 24296956
TI  - Clinical performance of a new hybrid contact lens for keratoconus.
AB  - OBJECTIVES: To compare the clinical performance of the Clearkone hybrid contact
      lens for the treatment of keratoconus against the habitual contact lens of the
      patients. METHODS: A total of 33 eyes from 18 patients were fitted with the
      Clearkone. High- and low-contrast visual acuity (HCVA and LCVA), central corneal
      thickness (CCT), and contrast sensitivity acuity (CSF) were recorded with
      habitual lenses (prestudy visit) and after 1 week, 15 days, and 1 month of wear
      of prescribed Clearkone. Subjective vision and comfort were rated using visual
      analogue scales (VAS). RESULTS: Three patients discontinued the study, one
      because of diffuse corneal staining after 1 day of use and the other two because
      of extreme discomfort. The rest of the patients completed the 1-month study. High
      contrast visual acuity and LCVA (logMAR) improved significantly from 0.16 +/-
      0.12 and 0.44 +/- 0.22, respectively, with the patient's habitual contact lenses
      to -0.006 +/- 0.058 and 0.23 +/- 0.13 after 1 day wearing Clearkone, remaining
      significant during all follow-up visits (P<0.001; repeated measures analysis of
      variance [RM-ANOVA]). There were no statistically significant differences in the
      mean CCT. The improvement of CSF was statistically significant with hybrid
      contact lenses prescribed compared with the patient's habitual contact lenses
      (P<0.001; RM-ANOVA test). Improvement in VAS score, with prescribed Clearkone,
      was statistically significant for comfort (P=0.043; RM-ANOVA test), but not for
      the subjective vision (P=0.759; RM-ANOVA test). CONCLUSIONS: Clearkone provides
      an improvement in visual acuity, contrast sensitivity, and subjective comfort in
      patients with keratoconus when compared with other contact lens options. However,
      clinicians must get specific training to fit the lens and be aware of potential
      adverse events.

PMID- 24296957
TI  - Short-term clinical comparison of two dual-disinfection multipurpose disinfecting
      solutions.
AB  - OBJECTIVE: To compare the short-term clinical performance of two dual
      disinfectant multipurpose disinfecting solutions (MPDS) when used in conjunction
      with two silicone hydrogel contact lenses. METHODS: Participants wore galyfilcon
      A and balafilcon A lenses, randomly allocated one type to each eye. Multipurpose
      disinfecting solutions were double-masked and allocated using a randomized
      crossover design. Lenses were presoaked overnight in the allocated MPDS,
      containing either polyquaternium-1/alexidine dihydrochloride (PQ-alexidine) or
      polyquaternium-1/myristamidopropyl dimethylamine (PQ-MAPDA). Lenses were worn
      daily for 4 days and disinfected with the same MPDS in which they had been
      soaked. Clinical assessments occurred immediately after insertion, 2 hours after
      insertion, and after 2 hours of wear on day 4. Subjective ratings were collected
      at each assessment and after 6 hours of wear on days 1 to 3. Linear mixed models
      were used for statistical analysis. RESULTS: Solution-induced corneal staining
      (SICS) incidence was significantly different between MPDS lens combinations
      (P=0.01) with PQ-MAPDA-balafilcon A showing the highest incidence (27.8%). The
      incidence of SICS was significantly higher when balafilcon A lenses were worn
      compared with galyfilcon A (19.4% vs. 2.8%; P=0.04). There was no significant
      difference in SICS incidence between MPDS (PQ-alexidine=5.6%, PQ-MAPDA=16.7%;
      P=0.08). Polyquaternium-1/alexidine dihydrochloride was associated with
      significantly fewer symptoms of burning/stinging (9.7+/-0.6 vs. 9.1+/-2.2;
      P=0.03) and self-assessed redness (9.8+/-0.5 vs. 9.2+/-1.9; P=0.03) on initial
      lens insertion. There were no significant differences between MPDS for comfort
      ratings (P>0.05). CONCLUSION: These short-term clinical results provide an
      initial indication that PQ-alexidine is associated with fewer symptoms on
      insertion but no significant difference in ocular comfort compared with PQ-MAPDA.
      Longer studies are required to provide further evidence.

PMID- 24296958
TI  - Propofol and dexmedetomidine for monitored anesthesia care during laser in situ
      keratomileusis.
AB  - BACKGROUND: The safety and efficacy of dexmedetomidine during laser in situ
      keratomileusis (LASIK) in stressed patients under topical anesthesia has not been
      fully investigated. METHODS: We randomized 30 adult patients with ametropia, with
      a Self-Rating Anxiety Scale score greater than 50, who were undergoing LASIK to
      receive dexmedetomidine (DEX group), propofol (P group), or placebo. No
      differences in baseline characteristics were observed between the groups. In the
      DEX group, dexmedetomidine was loaded (0.3 MUg/kg) before superficial anesthesia
      for eye surgery. Mean arterial pressure, heart rate (HR), oxygen saturation
      (SpO2), bispectral index (BIS) monitoring, and end-tidal CO2 were recorded before
      infusion (baseline) and every 5 minutes after loading of the study drugs. The
      degree of sedation was evaluated using the Ramsay Sedation Scale by an
      anesthesiologist who was unaware of the type of sedative used. The satisfaction
      of the patients and surgeon was assessed immediately after surgery using a 7
      point Likert-like verbal rating scale. RESULTS: Significantly lower HR was
      observed over time in the DEX group compared with the P group. No significant
      differences in SpO2 were observed between the groups. Bispectral index scores
      decreased at 10, 15, and 20 minutes after infusion. The surgeon's satisfaction
      scores were higher in the DEX group than in the P group. Recovery times were
      longer in DEX group than in the P group. CONCLUSIONS: Dexmedetomidine in
      conjunction with topical anesthesia offered better conscious sedation for nervous
      patients during LASIK, but these patients required a longer recovery period.

PMID- 24296959
TI  - Review of complications associated with contact lenses from unregulated sources
      of supply.
AB  - OBJECTIVE: To review existing studies and case reports regarding complications
      associated with contact lenses (CLs) from unregulated sources of supply and to
      identify any relevant trends. METHODS: A systematic literature search was
      performed to locate publications concerning complications associated with CLs
      obtained from unregulated sources of supply. RESULTS: A total of 23 articles were
      identified that represent 70 individual cases. All 8 of the pre-2006 case reports
      originated from the United States and the United Kingdom, whereas from 2006
      onwards, only 2 of the 15 reports came from these locations. Over-the-counter
      supply accounted for 73% (51/70) of cases, whereas 17% (12/70) were borrowed or
      shared lenses and 6% (4/70) lenses were obtained through the Internet. Nearly,
      three quarters of patients (30/42, 71%) waited longer than 48 hours after the
      onset of symptoms before seeking medical attention; 10 patients waited longer
      than a week, and 5 longer than a month. Microbial keratitis (MK) was reported in
      43 (61%) patients, with permanent damage occurring in 72% (31/43) of patients
      followed to conclusion. Known risk factors associated for MK were present in all
      cases irrespective of whether the patients developed MK. CONCLUSIONS: There are
      various reasons to presume that the unregulated supply of CLs might result in the
      use of inappropriate lenses, increase the risk of poorer lens hygiene, and
      militate against the prompt treatment of any consequent complications. There is
      some indication that the introduction of regulations to control the supply of
      plano CLs has alleviated the level of complications.

PMID- 24296960
TI  - Necrotizing enterocolitis in small-for-gestational-age neonates: a matched case
      control study.
AB  - BACKGROUND: Small for gestational age (SGA) neonates are at increased risk of
      mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed
      information on the incidence and risk factors of NEC in SGA neonates is lacking.
      OBJECTIVE: This study aims to estimate the incidence of NEC in a large cohort of
      SGA neonates, compared to appropriate for gestational age (AGA) neonates.
      METHODS: We included all SGA neonates without congenital malformations admitted
      to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were
      matched for gestational age with a control group of AGA neonates admitted during
      the same study period. We recorded the occurrence of NEC and studied the
      association with SGA and other potential risk factors. RESULTS: A total of 475
      SGA neonates were matched for gestational age at birth to 475 control AGA
      neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3%
      (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of
      NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7%
      (5/1.07) and 3.2% (5/153), respectively (p = 0.531). CONCLUSIONS: The risk of
      development of NEC is more than twofold increased in SGA neonates compared to AGA
      neonates. We found no association between the severity of SGA and NEC.

PMID- 24296961
TI  - MRI follow-up after 24 h is an accurate surrogate parameter for treatment success
      after thrombolysis.

PMID- 24296962
TI  - The innate immune system after ischemic injury: lessons to be learned from the
      heart and brain.
AB  - Innate immune cells are critically involved in ischemic complications of
      atherosclerosis. While new insight emerged on the origin and role of leukocytes
      in steady state, the knowledge about myeloid cells' sources, functions, and fate
      after stroke is limited. In our review, we highlight open questions in this
      important area while examining potential parallels in the immune response after
      stroke and myocardial infarction. We stress the need to better understand
      systemic interactions between ischemic tissue, immunity, and hematopoiesis, as
      turnover of leukocytes in inflammatory sites can be rapid, and cell production
      and supply may serve as future therapeutic targets to modulate inflammation in
      the vessel wall, brain, and heart. 

PMID- 24296963
TI  - Incidence of acute postoperative infections requiring reoperation after
      arthroscopic shoulder surgery.
AB  - BACKGROUND: An acute infection after arthroscopic shoulder surgery is a rare but
      serious complication. Previous studies estimating the incidence of infections
      after arthroscopic surgery have been conducted, but the majority of these had
      either relatively small study groups or were not specific to shoulder
      arthroscopic surgery. PURPOSE: To investigate the incidence of acute infections
      after arthroscopic shoulder surgery and compare infection rates by age group,
      sex, geographic region, and specific procedures. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: A retrospective review of a large insurance company
      database was performed for all shoulder arthroscopic surgeries performed in the
      United States between 2004 and 2009 that required additional surgery for
      infections within 30 days. The data were stratified by sex, age group, and
      region. Data were also stratified for specific procedures (capsulorrhaphy,
      treatment for superior labrum anterior-posterior tears, claviculectomy,
      decompression, and rotator cuff repair) and used to assess the variation in the
      incidence of infections across different arthroscopic shoulder procedures. Linear
      regression was used to determine the significance of differences in the data from
      year to year. chi(2) analysis was used to assess the statistical significance of
      variations among all groups. Poisson regression analysis with exposure was used
      to determine significant differences in a pairwise comparison between 2 groups.
      RESULTS: The total number of arthroscopic shoulder surgeries performed was
      165,820, and the number of infections requiring additional surgery was 450,
      resulting in an overall infection rate of 0.27%. The incidence of infections
      varied significantly across age groups (P < .001); the infection rate was highest
      in the >=60-year age group (0.36%) and lowest in the 10- to 39-year age group
      (0.18%). The incidence of infections also varied by region (P < .001); the
      incidence was highest in the South (0.37%) and lowest in the Midwest (0.11%). The
      incidence of infection treatments was also significantly different between
      different arthroscopic procedures (P < .01) and was highest for rotator cuff
      repair (0.29%) and lowest for capsulorrhaphy (0.16%). The incidence did not
      significantly vary by year or sex. CONCLUSION: The overall infection rate for all
      arthroscopic shoulder procedures was 0.27%. The incidence was highest in elderly
      patients, in the South, and for rotator cuff repair. The incidence was lowest in
      young patients, in the Midwest, and for capsulorrhaphy. In general, shoulder
      arthroscopic surgery in this study population had a low rate of reoperation in
      the acute period.

PMID- 24296964
TI  - Combined plasmonic and upconversion rear reflectors for efficient dye-sensitized
      solar cells.
AB  - A novel rear reflector structure that combines NIR light harvesting beta
      NaGdF4:Yb, Er, Fe upconversion nanoparticles (UCNPs) and light reflecting silver
      particles has been successfully used to improve the performance of dye-sensitized
      solar cells (DSSCs). The power conversion efficiency of DSSCs with a rear
      reflector was 7.04%, which is an increase of 21.3% compared to the cell without a
      rear reflector (5.8%). 

PMID- 24296965
TI  - Debt and depression among the Dibao population in northwestern China.
AB  - BACKGROUND: With the rapid development of economy, depression disorder is not
      only a public health issue but also a socioeconomic problem and attracting more
      and more attention in China. AIMS: The target of this study is to examine the
      prevalence of depression and the related risk factors in the Dibao population in
      northwestern China. METHOD: A cross-sectional analysis in a random sample survey
      conducted in three northwestern Chinese cities in 2007. The data from 4459
      respondents with completed Center for Epidemiological Studies-Depression (CES-D)
      scales were evaluated to explore the key risk factors for depression. Using
      depression as a binary variable according to the cutoff of the CES-D score and
      then as a continuous variable, multiple logistic and line regression analysis
      were performed to compare the odds ratio and the weight of different risk factors
      for depression. RESULTS: The prevalence of depression in non-Dibao population was
      34.7% but that in the Dibao population was 50.0% (p < .001). After adjusting for
      important confounders, Dibao population had an odds ratio (OR) of 1.38 (95%
      confidence interval (CI): 1.16-1.63) to have possible depression compared to
      those non-Dibao people. Furthermore, depression was associated with a higher OR
      of indebtedness (OR: 1.59, 95% CI: 1.31-1.93), and a small amount of debt would
      increase the possibility of depression for Dibao people (OR: 1.69, 95% CI: 1.28
      2.23). In addition, gender, body mass index (BMI), tobacco use and social network
      were also important risk factors for depression in the Dibao population. Using
      depression as a continuous variable, being a member of the Dibao population and
      being indebted will add 2.06 and 1.83 to the CES-D score, respectively, compared
      with the non-Dibao population and not being indebted. A comparison of the odds
      ratios of depression between the Dibao and the non-Dibao population showed that
      factors such as gender, BMI, tobacco use, social network and indebtedness were
      statistically significant in the Dibao population but were not statistically
      significant in the non-Dibao population. Additionally, having a savings account
      was statistically significant in the non-Dibao population but not in the Dibao
      population. CONCLUSIONS: It was not surprising, as proved by other studies, that
      gender, obesity and social network were risk factors associated with depression
      in the Dibao population. Our findings indicated that a small amount of
      indebtedness was also closely related to depression in the Dibao population.

PMID- 24296966
TI  - Primary care physicians' and psychiatrists' willingness to refer to religious
      mental health providers.
AB  - BACKGROUND: Recent decades have witnessed some integration of mental health care
      and religious resources. AIM: We measured primary care physicians' (PCPs) and
      psychiatrists' knowledge of religious mental health-care providers, and their
      willingness to refer there. METHODS: A national survey of PCPs and psychiatrists
      was conducted, using vignettes of depressed and anxious patients. Vignettes
      included Christian or Jewish patients, who regularly or rarely attended services.
      We asked whether physicians knew of local religious mental health providers, and
      whether they would refer patients there. RESULTS: In all, 896/1427 PCPs and
      312/487 psychiatrists responded. Half of PCPs (34.1%-44.1%) and psychiatrists
      (51.4%-56.3%) knew Christian providers; fewer PCPs (8.5%-9.9%) and psychiatrists
      (15.8%-19.6%) knew Jewish providers. Predictors included the following: patients
      were Christian (odds ratio (OR) = 2.2-2.9 for PCPs, 2.3-2.4 for psychiatrists),
      respondents were Christian (OR = 2.1-9.3 for PCPs) and respondents frequently
      attend services (OR = 3.5-7.0 for PCPs). Two-thirds of PCPs (63.3%-64%) and
      psychiatrists (48.8%-52.6%) would refer to religious providers. Predictors
      included the following: patients regularly attend services OR = 1.2 for PCPs, 1.6
      for Psychiatrists, depression vignette only), respondents were Christian (OR =
      2.8-18.1 for PCPs, 2.3-9.2 for psychiatrists) and respondents frequently attend
      services (OR = 5.1-6.3 for PCPs). CONCLUSION: Many physicians would refer
      patients to religious mental health providers. However, less religious PCPs are
      less knowledgeable about local religious providers.

PMID- 24296967
TI  - Is ophthalmic follow-up of premature infants necessary?

PMID- 24296968
TI  - Amblyopia in children referred with congenital dacryostenosis from the Arabian
      Peninsula.

PMID- 24296969
TI  - Treatment of anisometropic amblyopia.

PMID- 24296970
TI  - White and large corneas in the newborn nursery.

PMID- 24296971
TI  - Consecutive esotropia following surgery for intermittent exotropia.

PMID- 24296972
TI  - Ocular involvement in proteus syndrome.

PMID- 24296973
TI  - New developments in the treatment of acute pain after thoracic surgery.
AB  - PURPOSE OF REVIEW: This review examines recent advances and findings in the field
      of pain management in patients undergoing thoracic surgery. RECENT FINDINGS:
      Acute and chronic postoperative pain continues to remain a major problem and a
      primary concern for patients. Although thoracic epidural analgesia is still
      considered a 'gold standard', more evidence exists that paravertebral blockade
      has similar efficacy with a better side-effect and safety profile. The
      cornerstone of pain management remains a multimodal therapeutic strategy that
      provides both a central and a peripheral block by combining regional techniques
      with opioid and nonopioid analgesics. SUMMARY: Pain after thoracic surgery has a
      profound impact on perioperative outcome. Beyond the immediate perioperative
      period, acute pain contributes to the development of the debilitating chronic
      pain syndrome. Going forward, both procedural and pharmacologic interventions for
      acute and chronic pain should be studied in definitive multicenter, well designed
      randomized clinical trials.

PMID- 24296975
TI  - Nicotine consumption is regulated by a human polymorphism in dopamine neurons.
AB  - Smoking is the most important preventable cause of morbidity and mortality
      worldwide. Recent genome-wide association studies highlighted a human haplotype
      on chromosome 15 underlying the risk for tobacco dependence and lung cancer.
      Several polymorphisms in the CHRNA3-CHRNA5-CHRNB4 cluster coding for the
      nicotinic acetylcholine receptor (nAChR) alpha3, alpha5 and beta4 subunits were
      implicated. In mouse models, we define a key role in the control of sensitivity
      to nicotine for the alpha5 subunit in dopaminergic (DAergic) neurons of the
      ventral tegmental area (VTA). We first investigated the reinforcing effects of
      nicotine in drug-naive alpha5(-/-) mice using an acute intravenous nicotine self
      administration task and ex vivo and in vivo electrophysiological recordings of
      nicotine-elicited DA cell activation. We designed lentiviral re-expression
      vectors to achieve targeted re-expression of wild-type or mutant alpha5 in the
      VTA, in general, or in DA neurons exclusively. Our results establish a crucial
      role for alpha5*-nAChRs in DAergic neurons. These receptors are key regulators
      that determine the minimum nicotine dose necessary for DA cell activation and
      thus nicotine reinforcement. Finally, we demonstrate that a single-nucleotide
      polymorphism, the non-synonymous alpha5 variant rs16969968, frequent in many
      human populations, exhibits a partial loss of function of the protein in vivo.
      This leads to increased nicotine consumption in the self-administration paradigm.
      We thus define a critical link between a human predisposition marker, its
      expression in DA neurons and nicotine intake. 

PMID- 24296976
TI  - Association of metabolically healthy obesity with depressive symptoms: pooled
      analysis of eight studies.
AB  - The hypothesis of metabolically healthy obesity posits that adverse health
      effects of obesity are largely avoided when obesity is accompanied by a favorable
      metabolic profile. We tested this hypothesis with depressive symptoms as the
      outcome using cross-sectional data on obesity, metabolic health and depressive
      symptoms. Data were extracted from eight studies and pooled for individual
      participant meta-analysis with 30,337 men and women aged 15-105 years (mean
      age=46.1). Clinic measures included height, weight and metabolic risk factors
      (high blood pressure, high triglycerides, low high-density lipoprotein
      cholesterol, high C-reactive protein and high glycated hemoglobin). Depressive
      symptoms were assessed using clinical interview or standardized rating scales.
      The pooled sample comprised 7673 (25%) obese participants (body mass index ?30 kg
      m(-2)). Compared to all non-obese individuals, the OR for depressive symptoms was
      higher in metabolically unhealthy obese individuals with two or more metabolic
      risk factors (1.45; 95% confidence interval (CI)=1.30, 1.61) and for
      metabolically healthy obese with ?1 metabolic risk factor (1.19; 95% CI=1.03,
      1.37), adjusted for sex, age and race/ethnicity. Metabolically unhealthy obesity
      was associated with higher depression risk (OR=1.23; 95% CI=1.05, 1.45) compared
      with metabolically healthy obesity. These associations were consistent across
      studies with no evidence for heterogeneity in estimates (all I(2)-values<4%). In
      conclusion, obese persons with a favorable metabolic profile have a slightly
      increased risk of depressive symptoms compared with non-obese, but the risk is
      greater when obesity is combined with an adverse metabolic profile. These
      findings suggest that metabolically healthy obesity is not a completely benign
      condition in relation to depression risk.

PMID- 24296977
TI  - Type I interferon signaling genes in recurrent major depression: increased
      expression detected by whole-blood RNA sequencing.
AB  - A study of genome-wide gene expression in major depressive disorder (MDD) was
      undertaken in a large population-based sample to determine whether altered
      expression levels of genes and pathways could provide insights into biological
      mechanisms that are relevant to this disorder. Gene expression studies have the
      potential to detect changes that may be because of differences in common or rare
      genomic sequence variation, environmental factors or their interaction. We
      recruited a European ancestry sample of 463 individuals with recurrent MDD and
      459 controls, obtained self-report and semi-structured interview data about
      psychiatric and medical history and other environmental variables, sequenced RNA
      from whole blood and genotyped a genome-wide panel of common single-nucleotide
      polymorphisms. We used analytical methods to identify MDD-related genes and
      pathways using all of these sources of information. In analyses of association
      between MDD and expression levels of 13 857 single autosomal genes, accounting
      for multiple technical, physiological and environmental covariates, a significant
      excess of low P-values was observed, but there was no significant single-gene
      association after genome-wide correction. Pathway-based analyses of expression
      data detected significant association of MDD with increased expression of genes
      in the interferon alpha/beta signaling pathway. This finding could not be
      explained by potentially confounding diseases and medications (including
      antidepressants) or by computationally estimated proportions of white blood cell
      types. Although cause-effect relationships cannot be determined from these data,
      the results support the hypothesis that altered immune signaling has a role in
      the pathogenesis, manifestation, and/or the persistence and progression of MDD. 

PMID- 24296980
TI  - Defect controlled magnetism in FeP/graphene/Ni(111).
AB  - Spin switching of organometallic complexes by ferromagnetic surfaces is an
      important topic in the area of molecular nanospintronics. Moreover, graphene has
      been shown as a 2D surface for physisorption of molecular magnets and strain
      engineering on graphene can tune the spin state of an iron porphyrin (FeP)
      molecule from S = 1 to S = 2. Our ab initio density functional calculations
      suggest that a pristine graphene layer placed between a Ni(111) surface and FeP
      yields an extremely weak exchange interaction between FeP and Ni whereas the
      introduction of defects in graphene shows a variety of ferromagnetic and
      antiferromagnetic exchange interactions. Moreover, these defects control the easy
      axes of magnetization, strengths of magnetic anisotropy energies and spin-dipolar
      contributions. Our study suggests a new way of manipulating molecular magnetism
      by defects in graphene and hence has the potential to be explored in designing
      spin qubits to realize logic operations in molecular nanospintronics. 

PMID- 24296978
TI  - Inhibition of IL-6 expression in LNCaP prostate cancer cells by a combination of
      atorvastatin and celecoxib.
AB  - In the present study, we investigated the effect of a combination of atorvastatin
      and celecoxib on the formation of interleukin (IL)-6, a cytokine that is
      increased during the progression of LNCaP tumors from androgen dependence to
      androgen independence. Culturing LNCaP cells in androgen-depleted (AD) medium
      increased the levels of IL-6 and survivin, and treatment of the cells in AD
      medium with a combination of atorvastatin and celecoxib strongly inhibited the
      increase in IL-6 and survivin which is one of the downstream targets of the IL-6
      signaling pathway. Addition of recombinant IL-6 partially abrogated the combined
      effect of atorvastatin and celecoxib on apoptosis in LNCaP cells cultured in AD
      medium. In SCID mice, we found that the levels of IL-6 and survivin expression
      were increased when LNCaP tumors became androgen-independent. Treatment of the
      mice with atorvastatin or celecoxib alone caused decrease in the levels of IL-6
      and survivin as LNCaP tumors became androgen-independent, but treatment of the
      mice with a combination of celecoxib and atorvastatin resulted in a much stronger
      inhibition in the increase in IL-6 and survivin expression. Our results indicate
      that decreases in IL-6 and survivin levels by atorvastatin and celecoxib
      administration are associated with increased apoptosis in LNCaP cells treated
      with this drug combination. Our in vivo studies indicate that the inhibitory
      effect of a combination of atorvastatin and celecoxib on the progression of
      androgen-dependent LNCaP xenograft tumors to androgen independence is associated
      with inhibition of the increase in IL-6 and survivin that occurs when androgen
      dependent LNCaP prostate tumors become androgen-independent.

PMID- 24296982
TI  - Idiopathic pulmonary fibrosis: recent trials and current drug therapy.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with
      increasing incidence; the median survival is only 35 months and as yet no therapy
      has been proven to prolong survival. Recent unexpected randomised controlled
      trial (RCT) results and the conflicting evaluations of drug efficacy by
      regulatory agencies when considering the approval of pirfenidone have emphasised
      that we remain in the first stages of both our understanding of disease-relevant
      therapeutic targets and in our ability to investigate these putative targets with
      well-designed RCT. Three phase III trials are, however, anticipated to report
      results in 2014 and there is cautious optimism that we may be entering an era of
      mechanism-based anti-fibrotic therapies proven by large RCT to modify disease
      progression. We must now address how to practically translate these therapies
      safely and with maximal efficacy from a homogenous RCT population to the 'real
      life' heterogeneous population of patients with IPF. The role of a formal multi
      disciplinary team meeting in a specialist centre with expertise in IPF is key to
      this. New methodological and ethical research challenges will arise as we enter
      an era of potential combination therapy; standardized, robust RCT design will be
      central to meeting these challenges if we are to enable ongoing progress in our
      aim of increasing both the length and quality of life of patients with IPF.

PMID- 24296981
TI  - Conditioned media from macrophages of M1, but not M2 phenotype, inhibit the
      proliferation of the colon cancer cell lines HT-29 and CACO-2.
AB  - Solid tumors are infiltrated by stroma cells including macrophages and these
      cells can affect tumor growth, metastasis and angiogenesis. We have investigated
      the effects of conditioned media (CM) from different macrophages on the
      proliferation of the colon cancer cell lines HT-29 and CACO-2. CM from THP-1
      macrophages and monocyte-derived human macrophages of the M1 phenotype, but not
      the M2 phenotype, inhibited proliferation of the tumor cells in a dose-dependent
      manner. Lipopolysaccaharide and interferon gamma was used for differentiation of
      macrophages towards the M1 phenotype and CM were generated both during
      differentiation (M1DIFF) and after differentiation (M1). M1 and M1DIFF CM as well
      as THP-1 macrophage CM resulted in cell cycle arrest in HT-29 cells with a
      decrease of cells in S phase and an increase in G2/M phase. Treatment of HT-29
      cells with M1DIFF, but not M1 or THP-1 macrophage CM, resulted in apoptosis of
      about 20% of the tumor cells and this was accompanied by lack of recovery of cell
      growth after removal of CM and subsequent culture in fresh media. A protein array
      was used to identify cytokines released from M1 and M2 macrophages. Among the
      cytokines released by M1 macrophages, tumor necrosis factor alpha and CXCL9 were
      tested by direct addition to HT-29 cells, but neither affected proliferation. Our
      results indicate that M1 macrophages inhibit colon cancer cell growth and have
      the potential of contributing to reducing tumor growth in vivo.

PMID- 24296983
TI  - Characterization of red blood cell deformability change during blood storage.
AB  - Stored red blood cells (RBCs) show progressive deformability changes during blood
      banking/storage. Their deformability changes over an 8 weeks' storage period were
      measured using a microfluidic device. Hydrodynamic focusing controls the
      orientation and position of individual RBCs within the microchannel. High-speed
      imaging (5000 frames s(-1)) captures the dynamic deformation behavior of the
      cells, and together with automated image analysis, enables the characterization
      of over 1000 RBCs within 3 minutes. Multiple parameters including deformation
      index (DI), time constant (shape recovery rate), and RBC circularity were
      quantified. Compared to previous studies on stored RBC deformability, our results
      include a significantly higher number of cells (>1000 cells per sample vs. a few
      to tens of cells per sample) and, for the first time, reveal deformation changes
      of stored RBCs when traveling through human-capillary-like microchannels.
      Contrary to existing knowledge, our results demonstrate that the deformation
      index of RBCs under folding does not change significantly over blood storage.
      However, significant differences exist in time constants and circularity
      distribution widths, which can be used to quantify stored RBC quality or age. 

PMID- 24296984
TI  - The use of robotic endovascular catheters in the facilitation of transcatheter
      aortic valve implantation.
AB  - OBJECTIVES: The use of transcatheter aortic valve implantation (TAVI) is rapidly
      increasing with advances in technology and improved clinical outcomes. Adoption
      of robotic catheter technologies could have a role in TAVI, in different stages
      of the procedure, to improve endovascular tool manipulation and potentially
      reduce the risk of cerebral embolization. The aim was to determine whether there
      are advantages in using a robotic catheter for TAVI in the initial stages of the
      procedure; aortic arch navigation and valve crossing. METHODS: A silicone in
      vitro model of the aorta and stenotic aortic valve was developed. Fifteen
      operators performed the fluoroscopy-guided simulation using manual and robotic
      techniques. Performance metrics-time and vessel wall contact (wall-hits) were
      compared (Wilcoxon's signed-rank test). RESULTS: Overall, the time taken for
      robotic arch navigation was increased (3.09 min interquartile range (1.24-6.29)
      vs 1.21 min (0.15-4.42); P = 0.03). Contact with the aortic arch wall, however,
      significantly decreased using the robotic catheter: wall-hits 1 (0-5) vs 6 (2
      22), P < 0.01. For valve crossing, there was no significant increase in time and
      wall-hits when using the robotic technology. CONCLUSIONS: Use of robotic catheter
      technology is feasible in the initial stages of TAVI. Although it takes longer,
      robotic navigation reduces contact with the aortic arch wall, potentially
      reducing the embolic risk during endovascular manipulation. Using a robotic
      catheter is possible without increasing the number of wall-hits during valve
      crossing. This may provide a stable platform for wire positioning in the
      ventricle. With improvements in technology, perhaps allowing valve deployment,
      the stability and accuracy of the robotic arm may further improve performance.

PMID- 24296985
TI  - The ARCH Projects: design and rationale (IAASSG 001).
AB  - OBJECTIVE: A number of factors limit the effectiveness of current aortic arch
      studies in assessing optimal neuroprotection strategies, including insufficient
      patient numbers, heterogenous definitions of clinical variables, multiple
      technical strategies, inadequate reporting of surgical outcomes and a lack of
      collaborative effort. We have formed an international coalition of centres to
      provide more robust investigations into this topic. METHODS: High-volume aortic
      arch centres were identified from the literature and contacted for recruitment. A
      Research Steering Committee of expert arch surgeons was convened to oversee the
      direction of the research. RESULTS: The International Aortic Arch Surgery Study
      Group has been formed by 41 arch surgeons from 10 countries to better evaluate
      patient outcomes after aortic arch surgery. Several projects, including the
      establishment of a multi-institutional retrospective database, randomized
      controlled trials and a prospectively collected database, are currently underway.
      CONCLUSIONS: Such a collaborative effort will herald a turning point in the
      surgical management of aortic arch pathologies and will provide better powered
      analyses to assess the impact of varying surgical techniques on mortality and
      morbidity, identify predictors for neurological and operative risk, formulate and
      validate risk predictor models and review long-term survival outcomes and quality
      of-life after arch surgery.

PMID- 24296986
TI  - Equilibrium properties of the reaction H2 ? 2H by classical molecular dynamics
      simulations.
AB  - We have developed a classical molecular dynamics model for the hydrogen
      dissociation reaction, containing two- and three-particle potentials derived by
      Kohen, Tully and Stillinger. Two fluid densities were investigated for a wide
      range of temperatures, and 11 fluid densities were considered for one
      temperature. We report the temperature range where the degree of reaction is
      significant, and also where a stable molecule dominates the population in the
      energy landscape. The three-particle potential, which is essential for the
      reaction model and seldom studied, together with the two-particle interaction
      lead to a large effective excluded volume diameter of the molecules in the
      molecular fluid. The three-particle interaction was also found to give a large
      positive contribution to the pressure of the reacting mixture at high density
      and/or low temperatures. From knowledge of the dissociation constant of the
      reaction and the fluid pressure, we estimated the standard enthalpy of the
      dissociation reaction to be 430 kJ mol(-1) (rho = 0.0695 g cm(-3)) and 380 kJ
      mol(-1) (rho = 0.0191 g cm(-3)). These values are in good agreement with the
      experimental vaule of 436 kJ mol(-1) under ambient pressure. The model is
      consistent with a Lennard-Jones model of the molecular fluid, and may facilitate
      studies of the impact of chemical reactions on transport systems. 

PMID- 24296988
TI  - Arthroscopically assisted retrograde drilling of the humeral head with a guiding
      device.
AB  - This manuscript describes the successful treatment of a steroid-induced avascular
      necrosis of the humeral head using arthroscopically assisted retrograde drilling
      of a stage II lesion using a guiding device. At the final follow-up 19 month post
      operatively, the patient presented pain-free without functional limitations
      although the osteonecrosis had not been fully healed.

PMID- 24296989
TI  - Effect of VEGF-A165 addition on the integration of a cortical allograft in a
      tibial segmental defect in rabbits.
AB  - PURPOSE: Long-bone segmental defects caused by infection, fracture, or tumour are
      a challenge for orthopaedic surgeons. Structural allografts are sometimes used in
      their treatment but their poor biological characteristics are a liability. The
      objective of this study was to determine whether the addition of recombinant
      vascular endothelial growth factor-A (VEGF) to a structural allograft improved
      its integration into a rabbit tibial segmental defect in a non-union model.
      METHODS: Tibial segmental defects were filled with heat sterilized allogenic
      tubular tibiae sections and then stabilized with a screw plate. In the VEGF
      treatment group (n = 6 tibiae), 2 MUg of VEGF added to a 50 MUl matrigel solution
      was inserted into the allograft cavity. In the control group (n = 6 tibiae), only
      matrigel was added. After 12 weeks, macroscopic and microscopic analysis,
      radiographs, and computerized micro-tomography (micro-CT) were performed. If
      allograft consolidation was present, a torsional resistance analysis was
      performed. RESULTS: Addition of VEGF to the allograft decreased the rate of
      osteosynthesis failure compared with the control group (1/6 vs. 5/6, p = 0.08),
      increased trabecular continuity evaluated by micro-CT in the bone-allograft
      interphases (8/12 vs. 2/12, p = 0.036) and histological trabecular continuity
      (7/12 vs. 0/12, p = 0.0046). Full consolidation was observed in three tibiae of
      the VEGF group and one in the control group (differences not significant);
      however, torsional resistance showed no significant differences (n.s.).
      CONCLUSION: Addition of VEGF to a structural allograph inserted into a rabbit
      tibial segmental defect increased allograft integration rate. Further research in
      this direction might help clinicians in dealing with large bone defects.

PMID- 24296990
TI  - Sport-related concussions: time to diversify care and recommendation advice.

PMID- 24296991
TI  - Morphology of the femoral insertion site of the medial patellofemoral ligament.
AB  - PURPOSE: The purpose of this study was to identify the femoral insertion of the
      medial patellofemoral ligament (MPFL) and related osseous landmarks. METHODS: A
      total of 31 unpaired human cadaveric knees were studied. The MPFL was identified,
      and the site of its femoral insertion was marked. Three-dimensional images were
      created, and the location and morphology of the femoral insertion of the MPFL and
      related osseous structures were analyzed. RESULTS: The MPFL was identified in all
      knees. The femoral insertion of the MPFL was elliptical in shape, and the mean
      surface area was 56.5 +/- 16.9 mm(2). The characteristic features of the femoral
      insertion of the MPFL could not be identified, but the adductor tubercle was
      clearly identified in all knees. The centre of the femoral insertion of the MPFL
      was 10.6 +/- 2.5 mm distal to the apex of the adductor tubercle on the long axis
      of the femur, and the position of the insertion site was consistent in all knees.
      CONCLUSION: The adductor tubercle was clearly identified as an osseous landmark.
      The femoral insertion of the MPFL was approximately 10 mm distal to the adductor
      tubercle. These findings may improve understanding of the anatomy of the femoral
      insertion of the MPFL and may assist surgeons in performing anatomical
      reconstruction.

PMID- 24296992
TI  - Electrophysiological characterization of spontaneously contracting cell
      aggregates obtained from rainbow trout larvae with multielectrode arrays.
AB  - BACKGROUND/AIMS: Safety pharmacology requires novel model systems for the
      detection of cardiac side effects. Ranging from cell-based systems to model
      organisms, no model available to date reflects the complexity of the human heart
      and evokes the great need for improved and more affordable systems. Many drugs
      interact with hERG potassium channels and consequently cause life threatening
      ventricular arrhythmias, further highlighting the importance of suitable model
      systems. METHODS: Spontaneously Contracting Cell aggregates (SCC) as a 3D in
      vitro heart-syncytium obtained from rainbow trout larvae represent a novel model
      system for cardiac safety pharmacology. SCCs can be harvested cost-effectively
      and kept in culture for several weeks while retaining their functionality and
      displaying contraction rates similar to the human heart. RESULTS: Extracellular
      field potential recordings with multielectrode arrays revealed significant
      prolongation of field potential duration upon administration of common hERG
      potassium channel blockers. Infusion of 1 MUM Dofetilide and 10 MUM Terfenadine
      prolonged field potentials 10 fold and 2 fold, respectively. In addition, SCCs
      enabled analysis of autonomous contraction frequencies. CONCLUSION: Thus, SCCs
      represent a novel and low-cost cardiac model system of the human heart for
      application in safety pharmacology.

PMID- 24296993
TI  - Frequency of hematoma expansion after spontaneous intracerebral hemorrhage in
      children.
AB  - IMPORTANCE: Hematoma expansion is the only modifiable predictor of outcome in
      adult intracerebral hemorrhage; however, the frequency and clinical significance
      of hematoma expansion after childhood intracerebral hemorrhage are unknown.
      OBJECTIVE: To assess the frequency and extent of hematoma expansion in children
      with nontraumatic intracerebral hemorrhage. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective observational cohort study at 3 tertiary care pediatric hospitals.
      Children (>= 37 weeks' gestation to 18 years) with nontraumatic intracerebral
      hemorrhage were enrolled in a study from 2007 to 2012 focused on predictors of
      outcome. For this planned substudy of hematoma expansion, neonates 28 days or
      younger and participants with isolated intraventricular hemorrhage were excluded.
      Children with 2 head computed tomography (CT) scans within 48 hours were
      evaluated for hematoma expansion and were compared with children with only 1 head
      CT scan. Consent for the primary cohort was obtained from 73 of 87 eligible
      participants (84%); 41 of 73 children enrolled in the primary cohort met all
      inclusion/exclusion criteria for this substudy, in whom 22 had 2 head CT scans
      obtained within 48 hours that could be evaluated for hematoma expansion. Within
      our substudy cohort, 21 of 41 (51%) were male, 25 of 41 (61%) were white, 16 of
      41 (39%) were black, and median age was 7.7 years (interquartile range, 2.0-13.4
      years). MAIN OUTCOME AND MEASURE: Primary outcome was prevalence of hematoma
      expansion. RESULTS: Of 73 children, 41 (56%) met inclusion criteria, and 22 (30%)
      had 2 head CT scans to evaluate expansion. Among these 22 children, median time
      from symptom onset to first CT was 2 hours (interquartile range, 1.3-6.5 hours).
      Median baseline hemorrhage volume was 19.5 mL, 1.6% of brain volume. Hematoma
      expansion occurred in 7 of 22 (32%). Median expansion was 4 mL (interquartile
      range, 1-11 mL). Three children had significant (>33%) expansion; 2 required
      urgent hematoma evacuation. Expansion was not associated with poorer outcome.
      Compared with children with only 1 head CT scan within 48 hours, children with 2
      head CT scans had larger baseline hemorrhage volumes (P = .05) and were more
      likely to receive treatment for elevated intracranial pressure (P < .001).
      CONCLUSIONS AND RELEVANCE: Hematoma expansion occurs in children with
      intracerebral hemorrhage and may require urgent treatment. Repeat CT should be
      considered in children with either large hemorrhage or increased intracranial
      pressure.

PMID- 24296994
TI  - Quantifying melanin spatial distribution using pump-probe microscopy and a 2-D
      morphological autocorrelation transformation for melanoma diagnosis.
AB  - Pump-probe microscopy is an emerging molecular imaging technique that probes the
      excited state dynamics properties of pigmented samples. This method has been
      particularly intriguing for melanoma because, unlike other methods available, it
      can provide nondestructive, quantitative chemical information regarding different
      types of melanins, with high spatial resolution. In this Letter, we present a
      method based on mathematical morphology to quantify melanin structure (eumelanin,
      pheomelanin, and total melanin content, uniquely available with pump-probe
      microscopy) to aid in melanoma diagnosis. The approach applies a two-dimensional
      autocorrelation function and utilizes statistical parameters of the corresponding
      autocorrelation images, specifically, the second moments and entropy, to
      parameterize image structure. Along with bulk melanin chemical information, we
      show that this method can differentiate invasive melanomas from noninvasive and
      benign lesions with high sensitivity and specificity (92.3% and 97.5%,
      respectively, with N=53). The mathematical method and the statistical analysis
      are described in detail and results from cutaneous and ocular conjunctival
      melanocytic lesions are presented.

PMID- 24296996
TI  - On the birefringence of healthy and malaria-infected red blood cells.
AB  - The birefringence of a red blood cell (RBC) is quantitatively monitored as it
      becomes infected by a malarial parasite. Large changes occur in the cell's
      refractive index at different stages of malarial infection. The observed rotation
      of an optically trapped, malaria-infected RBC is not a simple function of shape
      distortion: the malarial parasite is found to itself exercise a profound
      influence on the rotational dynamics by inducing stage-specific birefringence.
      Our measurements shed new light on the competition between shape- and form
      birefringence in RBCs. We demonstrate the possibility of using birefringence to
      establish very early stages of infected parasites and of assessing various
      factors that contribute to birefringence in normal and infected cells. Our
      results have implications for the development and use of noninvasive techniques
      of quantifying changes in cell properties induced by malaria disease pathology.

PMID- 24296997
TI  - In vivo label-free microangiography by laser speckle imaging with intensity
      fluctuation modulation.
AB  - We present the theory of laser speckle imaging improved with intensity
      fluctuation modulation, where the dynamic speckle pattern can be isolated from
      its stationary counterpart. A series of in vivo experiments demonstrate the
      effectiveness of our method in achieving microangiography and monitoring vascular
      self-recovering process. All results show the convincing performance of our
      imaging method in both structural and functional imaging of blood flow, which may
      have potential applications in biological research and disease diagnosis.

PMID- 24296995
TI  - Optical measurement of arterial mechanical properties: from atherosclerotic
      plaque initiation to rupture.
AB  - During the pathogenesis of coronary atherosclerosis, from lesion initiation to
      rupture, arterial mechanical properties are altered by a number of cellular,
      molecular, and hemodynamic processes. There is growing recognition that
      mechanical factors may actively drive vascular cell signaling and regulate
      atherosclerosis disease progression. In advanced plaques, the mechanical
      properties of the atheroma influence stress distributions in the fibrous cap and
      mediate plaque rupture resulting in acute coronary events. This review paper
      explores current optical technologies that provide information on the mechanical
      properties of arterial tissue to advance our understanding of the mechanical
      factors involved in atherosclerosis development leading to plaque rupture. The
      optical approaches discussed include optical microrheology and traction force
      microscopy that probe the mechanical behavior of single cell and extracellular
      matrix components, and intravascular imaging modalities including laser speckle
      rheology, optical coherence elastography, and polarization-sensitive optical
      coherence tomography to measure the mechanical properties of advanced coronary
      lesions. Given the wealth of information that these techniques can provide,
      optical imaging modalities are poised to play an increasingly significant role in
      elucidating the mechanical aspects of coronary atherosclerosis in the future.

PMID- 24296998
TI  - Saturated excitation microscopy for sub-diffraction-limited imaging of cell
      clusters.
AB  - Saturated excitation (SAX) microscopy offers high-depth discrimination
      predominantly due to nonlinearity in the fluorescence response induced by the
      SAX. Calculation of the optical transfer functions and the edge responses for SAX
      microscopy revealed the contrast improvement of high-spatial frequency components
      in the sample structure and the effective reduction of background signals from
      the out-of-focus planes. Experimental observations of the edge response and x-z
      cross-sectional images of stained HeLa cells agreed well with theoretical
      investigations. We applied SAX microscopy to the imaging of three-dimensional
      cultured cell clusters and confirmed the resolution improvement at a depth of 40
      MUm. This study shows the potential of SAX microscopy for super-resolution
      imaging of deep parts of biological specimens.

PMID- 24296999
TI  - Schlieren laser Doppler flowmeter for the human optical nerve head with the
      flicker stimuli.
AB  - We describe a device to measure blood perfusion for the human optic nerve head
      (ONH) based on laser Doppler flowmetry (LDF) with a flicker stimuli of the fovea
      region. This device is self-aligned for LDF measurements and includes near
      infrared pupil observation, green illumination, and observation of the ONH. The
      optical system of the flowmeter is based on a Schlieren arrangement which
      collects only photons that encounter multiple scattering and are back-scattered
      out of the illumination point. LDF measurements are based on heterodyne detection
      of Doppler shifted back-scattered light. We also describe an automated analysis
      of the LDF signals which rejects artifacts and false signals such as blinks. By
      using a Doppler simulator consisting of a lens and a rotating diffusing wheel, we
      demonstrate that velocity and flow vary linearly with the speed of the wheel. A
      cohort of 12 healthy subjects demonstrated that flicker stimulation induces an
      increase of 17.8% of blood flow in the ONH.

PMID- 24297000
TI  - Nondestructive inspection of phase transformation in zirconia-containing hip
      joints by confocal Raman spectroscopy.
AB  - Environmental metastability of zirconia (ZrO2) ceramic in the human body
      [represented by a tetragonal-to-monoclinic (t->m) phase transformation] takes
      place on the surface of the artificial joint and proceeds with time toward its
      interior. Its quantitative characterization is mandatory for the safety of joint
      implants and consists of the assessment of the in-depth monoclinic profile
      fraction as compared to that of the initially untransformed material. We attempt
      to fully establish a characterization protocol and present two different
      nondestructive approaches for resolving highly graded phase-transformation
      profiles along the hip-joint subsurface by confocal Raman microprobe technique. A
      series of partially transformed tetragonal zirconia polycrystal and zirconia
      toughened alumina ceramics are used as screening samples. Probe biases could be
      eliminated and the real transformation profiles retrieved through a deconvolution
      procedure of Raman experimental data collected as a function of pinhole aperture
      and focal depth, respectively. Confirmation of the confocal assessments was made
      by a destructive cross-sectional inspection by both laser optical microscope and
      Raman spectral line scans. This study unveils for the first time the real
      quantitative amount of surface phase-transformation fractions and the related
      subsurface profiles in zirconia-based retrieved medical samples.

PMID- 24297001
TI  - Total synthesis of (S)-14-azacamptothecin.
AB  - A concise synthesis of (S)-14-azacamptothecin has been accomplished in 8 steps
      from commercially available (R)-2-hydroxybutanoic acid. The key strategy involved
      in this synthesis is the Michael addition/beta-elimination sequence to construct
      the chiral quaternary carbon center, followed by palladium catalyzed cyanation
      and formal [4 + 2] cycloaddition/elimination/aromatization in a one pot manner to
      form the pyrrolopyrimidin-4-one moiety. 

PMID- 24297004
TI  - Feasibility and preliminary findings of a church-based mother-daughter pilot
      study promoting physical activity among young Latinas.
AB  - Physical activity (PA) rates in young Latina girls are low. This study examined
      acceptability and feasibility of implementing a mother-daughter intervention
      targeting individual and family-level correlates of PA. Eleven mother-daughter
      dyads participated in an 8-week intervention promoting PA in preadolescents.
      Preliminary data suggest increases in self-report PA, reductions in television
      watching, and improvements in parenting and mother-daughter communication. Focus
      group data suggest that participants benefited from receiving the intervention in
      a group format. Findings suggest that mother-daughter interventions promoting PA
      in young Latinas are feasible. Physical activity may improve family communication
      and mother-daughter relations. 

PMID- 24297006
TI  - Fit and healthy family cAMP for engaging families in a child obesity
      intervention: a community health center pilot project.
AB  - Childhood obesity has become a significant problem in the United States,
      especially in poor communities, and we know that children who have at least 1
      obese parent have a much higher risk of being obese. Combined behavioral
      lifestyle interventions and family-based intervention programs to address
      pediatric obesity have the strongest evidence of effectiveness. In this pilot
      study, we delineate our collaborative model of family group medical visits at a
      community health center combined with healthy living workshops involving families
      with at least 1 child and 1 parent or guardian who are obese as a unique approach
      to address obesity in children. 

PMID- 24297005
TI  - Feasibility and preliminary outcomes from a pilot study of an integrated health
      mental health promotion program in school mental health services.
AB  - The prevalence of unmet health and mental health needs among youth has spurred
      the growing consensus to develop strategies that integrate services to promote
      overall well-being. This pilot study reports on the feasibility and outcomes of a
      theory-driven, family-focused, integrated health-mental health promotion program
      for underserved adolescents receiving school mental health services. Parent and
      adolescent assessments conducted prior to and following the brief, 6-session
      promotion program showed significant improvements in family support, youth self
      efficacy, health behaviors, and mental health outcomes. Clinician reports
      contributed to a characterization of the feasibility, acceptability, and future
      recommendations for the integrated program. 

PMID- 24297007
TI  - Partnering for success and sustainability in community-based child obesity
      intervention: seeking to help families ACT!
AB  - Sustaining community-based obesity interventions for families represents an
      ongoing challenge. Many initially grant-funded initiatives lack a sustainable
      model to continue. After initial grant funding ended, we continued a partnership
      between Seattle Children's Hospital and YMCA of Greater Seattle to enhance and
      expand a community-based family obesity program, "ACT! Actively Changing
      Together." We used principles of continuous process improvement, community-based
      participatory research, and the RE-AIM framework to successfully transition from
      a grant-funded to a community-supported program. Our pilot evaluation
      demonstrated promising results in parent behaviors, youth quality of life,
      ongoing family participation at the Y, and youth body mass index. 

PMID- 24297008
TI  - Developing programs for African families, by African families: engaging African
      migrant families in Melbourne in health promotion interventions.
AB  - Obesity is an emerging problem for African migrants in Australia, but few
      prevention programs incorporate their cultural beliefs and values. This study
      reports on the application of community capacity-building and empowerment
      principles in 4 workshops with Sudanese families in Australia. Workshop
      participants prioritized health behaviors, skill and knowledge gaps, and
      environments for change to identify culturally centered approaches to health
      promotion. The workshops highlighted a need for culturally and age-appropriate
      interventions that build whole-of-family skills and knowledge around the positive
      effects of physical activity and nutrition to improve health within communities
      while reducing intergenerational and gender role family conflicts. 

PMID- 24297009
TI  - The healthy start partnership: an approach to obesity prevention in young
      families.
AB  - This article investigates the impact of community-based interventions developed
      by the Healthy Start Partnership (HSP) to promote healthy body weights in
      families. Intercept surveys were conducted to monitor community exposure. A
      nonconcurrent, no treatment control design was used to assess population-level
      weight outcomes. Control (n = 219) and intervention (n = 276) cohorts of pregnant
      women were recruited and followed until 6 months postpartum. Data were collected
      through 2 self-administered questionnaires and medical record audits. Results
      indicate community residents were exposed to interventions. However, little
      evidence of positive effects of interventions on weight outcomes was found for
      mothers or infants. 

PMID- 24297010
TI  - Assessment of a healthy corner store program (FIT Store) in low-income, urban,
      and ethnically diverse neighborhoods in Michigan.
AB  - This study evaluated a community-based and social marketing healthy corner store
      program (FIT store) to improve the affordability and availability of healthy
      foods in low-income, urban, and ethnically diverse neighborhoods in Michigan. The
      Nutrition Environment Measures Survey in Stores data were analyzed for the FIT (N
      = 4) stores. Two cross-sectional surveys were conducted among the FIT store
      customers before (N = 401) and after (N = 318) the intervention. Three FIT stores
      improved their total Nutrition Environment Measures Survey in Stores availability
      score from before to after the intervention. A significantly higher level of FIT
      awareness and monthly bean and nut consumption was reported in the
      postintervention. 

PMID- 24297013
TI  - An analytical approach for scanning probe microscope-tip electrostatic field
      distribution accounting for dead layer and domain wall.
AB  - We have proposed a new theoretical approach for the determination of the electric
      field distribution in the ferroelectric/dielectric system with the presence of
      the SPM tip. The initial statement of the model has only a numerical solution. To
      find an analytical solution of the problem, some assumptions are introduced: the
      domain wall thickness can be considered to be much smaller than the domain size,
      and we use a high ferroelectric dielectric permittivity. The developed approach
      allows us to obtain explicit formulas for the polarization and electric field
      intensity. We have calculated and then analyzed the tip capacitance as a function
      of the distance from the ferroelectric interface. Additionally, different forms
      of the SPM tip are considered. It is demonstrated that in the presence of charges
      at the domain, the results differ from those obtained with the widely used
      dielectric model by 30%. 

PMID- 24297015
TI  - Viscoelastic response (VisR) imaging for assessment of viscoelasticity in Voigt
      materials.
AB  - Viscoelastic response (VisR) imaging is presented as a new acoustic radiation
      force (ARF)-based elastographic imaging method. Exploiting the Voigt model, VisR
      imaging estimates displacement in only the ARF region of excitation from one or
      two successive ARF impulses to estimate tausigma, the relaxation time for
      constant stress. Double-push VisR tausigma estimates were not statistically
      significantly different (p < 0.02) from those of shearwave dispersion ultrasound
      vibrometry (SDUV) or monitored steady-state excitation recovery (MSSER)
      ultrasound in six homogeneous viscoelastic tissue mimicking phantoms with elastic
      moduli ranging from 3.92 to 15.34 kPa and coefficients of viscosity ranging from
      0.87 to 14.06 Pa.s. In two-dimensional imaging, double-push VisR tausigma images
      discriminated a viscous spherical inclusion in a structured phantom with higher
      CNR over a larger axial range than single-push VisR or conventional acoustic
      radiation force impulse (ARFI) ultrasound. Finally, 2-D in vivo double-push VisR
      images in normal canine semitendinosus muscle were compared with spatially
      matched histochemistry to corroborate lower double-push VisR tausigma values in
      highly collagenated connective tissue than in muscle, suggesting double-push
      VisR's in vivo relevance to diagnostic imaging, particularly in muscle. The key
      advantages and disadvantages to VisR, including lack of compensation for inertial
      terms, are discussed.

PMID- 24297014
TI  - Acoustic radiation force beam sequence performance for detection and material
      characterization of atherosclerotic plaques: preclinical, ex vivo results.
AB  - This work presents preclinical data demonstrating performance of acoustic
      radiation force (ARF)-based elasticity imaging with five different beam sequences
      for atherosclerotic plaque detection and material characterization. Twelve
      trained, blinded readers evaluated parametric images taken ex vivo under
      simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver
      operating characteristic (ROC) curve analysis was carried out to quantify reader
      performance using spatially-matched immunohistochemistry for validation. The beam
      sequences employed had high sensitivity (sens) and specificity (spec) for
      detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec:
      86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%),
      collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens:
      92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas
      under the ROC curve (AUC), but was not statistically significantly higher than
      4:1 parallel-receive tracking. Excitation focal configuration did not result in
      statistically different AUCs. Overall, these results suggest ARF-based imaging is
      relevant to detecting and characterizing plaques and support its use for
      diagnosing and monitoring atherosclerosis. 

PMID- 24297017
TI  - Increasing the sonoporation efficiency of targeted polydisperse microbubble
      populations using chirp excitation.
AB  - The therapeutic use of microbubbles for targeted drug or gene delivery is a
      highly active area of research. Phospholipid- encapsulated microbubbles typically
      have a polydisperse size distribution over the 1 to 10 MUm range and can be
      functionalized for molecular targeting and loaded with drugcarrying liposomes.
      Sonoporation through the generation of shear stress on the cell membrane by
      microbubble oscillations is one mechanism that results in pore formation in the
      cell membrane and can improve drug delivery. A microbubble oscillating at its
      resonant frequency would generate maximum shear stress on a membrane. However,
      because of the polydisperse nature of phospholipid microbubbles, a range of
      resonant frequencies would exist in a single population. In this study, the use
      of linear chirp excitations was compared with equivalent duration and acoustic
      pressure tone excitations when measuring the sonoporation efficiency of targeted
      microbubbles on human colorectal cancer cells. A 3 to 7 MHz chirp had the
      greatest sonoporation efficiency of 26.9 +/- 5.6%, compared with 16.4 +/- 1.1%
      for the 1.32 to 3.08 MHz chirp. The equivalent 2.2- and 5-MHz tone excitations
      have efficiencies of 12.8 +/- 2.1% and 15.6 +/- 1.1%, respectively, which were
      all above the efficiency of 4.1 +/- 3.1% from the control exposure. 

PMID- 24297016
TI  - Two-dimensional image reconstruction with spectrally-randomized ultrasound
      signals.
AB  - An ultrasound imaging method using unfocused frequency-randomized transmissions
      and image reconstruction from data received by a single element is experimentally
      demonstrated. The elements of an ultrasound imaging array are randomly assigned
      different frequencies and driven by a multicycle sinusoidal burst. The resulting
      acoustic field is spectrally unique and target localization is possible based on
      the a priori knowledge of this field. A 64-element phased array driven by
      arbitrary waveform generators is used in the experiments. Transmission
      frequencies range from 2.00 to 2.64 MHz with 10 kHz resolution. One element of
      the array is reserved for receiving backscattered signals and an image is
      reconstructed from the signals received by this single element. Reconstruction is
      based on cross-correlation of the received data with transmitted bursts to obtain
      radial elliptical projections. Multiple projections are obtained from single
      received data, which are back-projected to obtain an image. Successful target
      localization is made possible through multiple frequency-randomized acquisitions.
      The performance of the method is measured using images of a single point target.
      These images are quantified and analyzed in terms of their point spread function
      (PSF) and SNR. Optimum imaging parameters, such as the number of acquisitions,
      transmit burst length, and number of possible receivers, are obtained through
      further analysis of SNR. Images obtained with the frequency-randomized
      transmission method compared well with the performance measurements of a typical
      B-mode acquisition. It is demonstrated that the frequency-randomized method
      provides images superior to B-mode images in terms of PSF. The two-point
      discrimination threshold is measured to be 2 mm in the lateral and azimuth
      directions.

PMID- 24297018
TI  - Multi-line acquisition with minimum variance beamforming in medical ultrasound
      imaging.
AB  - In recent years, multiple-line acquisition (MLA) has been introduced to increase
      frame rate in cardiac ultrasound medical imaging. However, this method induces
      blocklike artifacts in the image. One approach suggested, synthetic transmit
      beamforming (STB), involves overlapping transmit beams which are then
      interpolated to remove the MLA blocking artifacts. Independently, the application
      of minimum variance (MV) beamforming has been suggested in the context of MLA. We
      demonstrate here that each approach is only a partial solution and that combining
      them provides a better result than applying either approach separately. This is
      demonstrated by using both simulated and real phantom data, as well as cardiac
      data. We also show that the STB-compensated MV beamfomer outperforms single-line
      acquisition (SLA) delay- and-sum in terms of lateral resolution. 

PMID- 24297019
TI  - The effect of amplitude modulation on subharmonic imaging with chirp excitation.
AB  - Subharmonic generation from ultrasound contrast agents depends on the spectral
      and temporal properties of the excitation signal. The subharmonic response can be
      improved by using wideband and long-duration signals. However, for sinusoidal
      tone-burst excitation, the effective bandwidth of the signal is inversely
      proportional to the signal duration. Linear frequency-modulated (LFM) and
      nonlinear frequency-modulated (NLFM) chirp excitations allow independent control
      over the signal bandwidth and duration; therefore, in this study LFM and NLFM
      signals were used for the insonation of microbubble populations. The amplitude
      modulation of the excitation waveform was achieved by applying different window
      functions. A customized window was designed for the NLFM chirp excitation by
      focusing on reducing the spectral leakage at the subharmonic frequency and
      increasing the subharmonic generation from microbubbles. Subharmonic scattering
      from a microbubble population was measured for various excitation signals and
      window functions. At a peak negative pressure of 600 kPa, the generated
      subharmonic energy by ultrasound contrast agents was 15.4 dB more for NLFM chirp
      excitation with 40% fractional bandwidth when compared with tone-burst
      excitation. For this reason, the NLFM chirp with a customized window was used as
      an excitation signal to perform subharmonic imaging in an ultrasound flow
      phantom. Results showed that the NLFM waveform with a customized window improved
      the subharmonic contrast by 4.35 +/- 0.42 dB on average over a Hann-windowed LFM
      excitation.

PMID- 24297020
TI  - Ultrasonic characteristic of phase shift of layered structure and the
      determination of layer thickness.
AB  - For the ultrasonic normally-incident reflected method, the phase shift of the mid
      layer in a multi-layered structure has been theoretically derived and expressed
      as a sum form of the measured phase shift and the crossing phase shift. Using the
      sum form, the characteristics of phase shifts of a linear-viscoelastic layer on
      the two different elastic substrates of half-space of the infinite extent are
      first analyzed. By the replacement of phase shift of the upper elastic substrate
      with the corresponding measured phase shift, the substitution function of the
      input acoustical impedance of a next inaccessible layer has been developed. It is
      concluded that the corresponding relation of the layer phase shift with the
      minima/maxima of the absolute value of the input acoustical impedance of the
      inaccessible layer is repeated by those of the substitution function. Without
      giving the substrate thickness and considering the introduced misalignment and
      distortion problems, based on the corresponding relation, the thickness of the
      inaccessible layer can be determined by searching the frequencies of the minima/
      maxima of the absolute value of the substitution function. 

PMID- 24297021
TI  - Automated defect localization via low rank plus outlier modeling of propagating
      wavefield data.
AB  - This work proposes an agnostic inference strategy for material diagnostics,
      conceived within the context of laser-based nondestructive evaluation methods
      which extract information about structural anomalies from the analysis of
      acoustic wavefields measured on the structure's surface by means of a scanning
      laser interferometer. The proposed approach couples spatiotemporal windowing with
      low rank plus outlier modeling, to identify a priori unknown deviations in the
      propagating wavefields caused by material inhomogeneities or defects, using
      virtually no knowledge of the structural and material properties of the medium.
      This characteristic makes the approach particularly suitable for diagnostics
      scenarios in which the mechanical and material models are complex, unknown, or
      unreliable. We demonstrate our approach in a simulated environment using
      benchmark point and line defect localization problems based on propagating
      flexural waves in a thin plate. 

PMID- 24297022
TI  - Strain sensitivity model for guided waves in plates using the time-reversal
      technique.
AB  - The use of the time-reversal technique to detect variations in the external
      applied traction in a strip of aluminum plate is presented. Experiments have been
      performed in transmission-reception mode, using two fixed ultrasonic transducers
      near the ends of the plate. Two different parameters of the time-reversed signal
      are used for monitoring the strain state, the peak amplitude and the focusing
      time. The inverse filter technique was used in the transmitted signal to equalize
      the amplitude spectrum, enhancing the sensitivity in the focus amplitude by 5
      times. The external traction sensitivity was experimentally verified by using an
      aluminum plate (800 * 100 * 3 mm) and two 5-MHz ultrasonic transducers spaced 700
      mm apart. At the maximum strain state (180 MUstrain), the peak value was reduced
      by about 10% in the conventional process and by 50% using the inverse filter. To
      evaluate the effects of the strain in the time-reversal signal, a theoretical
      model was constructed. This model is successful in predicting the changes in the
      group delay and, consequently, the focusing time using a linear equation. This
      relationship can also be used to determine the strain level quantitatively. The
      experimental results show that the time-reversal signal technique can be used in
      practical monitoring of changes at the strain level in mechanical structures. 

PMID- 24297023
TI  - Super-resolution image reconstruction for ultrasonic nondestructive evaluation.
AB  - Ultrasonic testing is one of the most successful nondestructive evaluation (NDE)
      techniques for the inspection of carbon-fiber-reinforced polymer (CFRP)
      materials. This paper discusses the application of the iterative backprojection
      (IBP) super-resolution image reconstruction technique to carbon epoxy laminates
      with simulated defects to obtain high-resolution images for NDE. Super-resolution
      image reconstruction is an approach used to overcome the inherent resolution
      limitations of an existing ultrasonic system. It can greatly improve the image
      quality and allow more detailed inspection of the region of interest (ROI) with
      high resolution, improving defect evaluation and accuracy. First, three
      artificially simulated delamination defects in a CFRP panel were considered to
      evaluate and validate the application of the IBP method. The results of the
      validation indicate that both the contrast-tonoise ratio (CNR) and the peak
      signal-to-noise ratio (PSNR) value of the super-resolution result are better than
      the bicubic interpolation method. Then, the IBP method was applied to the low
      resolution ultrasonic C-scan image sequence with subpixel displacement of two
      types of defects (delamination and porosity) which were obtained by the micro
      scanning imaging technique. The result demonstrated that super-resolution images
      achieved better visual quality with an improved image resolution compared with
      raw C-scan images. 

PMID- 24297024
TI  - Investigation of capacitively coupled ultrasonic transducer system for
      nondestructive evaluation.
AB  - Capacitive coupling offers a simple solution to wirelessly probe ultrasonic
      transducers. This paper investigates the theory, feasibility, and optimization of
      such a capacitively coupled transducer system (CCTS) in the context of
      nondestructive evaluation (NDE) applications. The noncontact interface relies on
      an electric field formed between four metal plates-two plates are physically
      connected to the electrodes of a transducer, the other two are in a separate
      probing unit connected to the transmit/receive channel of the instrumentation.
      The complete system is modeled as an electric network with the measured impedance
      of a bonded piezoelectric ceramic disc representing a transducer attached to an
      arbitrary solid substrate. A transmission line model is developed which is a
      function of the physical parameters of the capacitively coupled system, such as
      the permittivity of the material between the plates, the size of the metal
      plates, and their relative positions. This model provides immediate prediction of
      electric input impedance, pulse-echo response, and the effect of plate
      misalignment. The model has been validated experimentally and has enabled
      optimization of the various parameters. It is shown that placing a tuning
      inductor and series resistor on the transmitting side of the circuit can
      significantly improve the system performance in terms of the signal-to-crosstalk
      ratio. Practically, bulk-wave CCTSs have been built and demonstrated for
      underwater and through-composite testing. It has been found that electrical
      conduction in the media between the plates limits their applications. 

PMID- 24297025
TI  - Reliable computation of roots in analytical waveguide modeling using an interval
      Newton approach and algorithmic differentiation.
AB  - For the modeling and simulation of wave propagation in geometrically simple
      waveguides such as plates or rods, one may employ the analytical global matrix
      method. That is, a certain (global) matrix depending on the two parameters
      wavenumber and frequency is built. Subsequently, one must calculate all parameter
      pairs within the domain of interest where the global matrix becomes singular. For
      this purpose, one could compute all roots of the determinant of the global matrix
      when the two parameters vary in the given intervals. This requirement to
      calculate all roots is actually the method's most concerning restriction.
      Previous approaches are based on so-called mode-tracers, which use the physical
      phenomenon that solutions, i.e., roots of the determinant of the global matrix,
      appear in a certain pattern, the waveguide modes, to limit the root-finding
      algorithm's search space with respect to consecutive solutions. In some cases,
      these reductions of the search space yield only an incomplete set of solutions,
      because some roots may be missed as a result of uncertain predictions. Therefore,
      we propose replacement of the mode-tracer approach with a suitable version of an
      interval- Newton method. To apply this interval-based method, we extended the
      interval and derivative computation provided by a numerical computing environment
      such that corresponding information is also available for Bessel functions used
      in circular models of acoustic waveguides. We present numerical results for two
      different scenarios. First, a polymeric cylindrical waveguide is simulated, and
      second, we show simulation results of a one-sided fluid-loaded plate. For both
      scenarios, we compare results obtained with the proposed interval-Newton
      algorithm and commercial software. 

PMID- 24297026
TI  - Analysis of signals propagating in a phononic crystal PZT layer deposited on a
      silicon substrate.
AB  - The design of a stop-band filter constituted by a periodically patterned lead
      zirconate titanate (PZT) layer, polarized along its thickness, deposited on a
      silicon substrate and sandwiched between interdigitated electrodes for
      emission/reception of guided elastic waves, is investigated. The filter
      characteristics are theoretically evaluated by using finite element simulations:
      dispersion curves of a patterned PZT layer with a specific pattern geometry
      deposited on a silicon substrate present an absolute stop band. The whole
      structure is modeled with realistic conditions, including appropriate
      interdigitated electrodes to propagate a guided mode in the piezoelectric layer.
      A robust method for signal analysis based on the Gabor transform is applied to
      treat transmitted signals; extract attenuation, group delays, and wave number
      variations versus frequency; and identify stop-band filter characteristics. 

PMID- 24297027
TI  - Micromachining techniques in developing high-frequency piezoelectric composite
      ultrasonic array transducers.
AB  - Several micromachining techniques for the fabrication of high-frequency
      piezoelectric composite ultrasonic array transducers are described in this paper.
      A variety of different techniques are used in patterning the active piezoelectric
      material, attaching backing material to the transducer, and assembling an
      electronic interconnection board for transmission and reception from the array.
      To establish the feasibility of the process flow, a hybrid test ultrasound array
      transducer consisting of a 2-D array having an 8 * 8 element pattern and a 5
      element annular array was designed, fabricated, and assessed. The arrays are
      designed for a center frequency of ~60 MHz. The 2-D array elements are 105 * 105
      MUm in size with 5-MUm kerfs between elements. The annular array surrounds the
      square 2-D array and provides the option of transmitting from the annular array
      and receiving with the 2-D array. Each annular array element has an area of 0.71
      mm(2) with a 16-MUm kerf between elements. The active piezoelectric material is
      (1 - x) Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT)/epoxy 1-3 composite with a PMN-PT
      pillar lateral dimension of 8 MUm and an average gap width of ~4 MUm, which was
      produced by deep reactive ion etching (DRIE) dry etching techniques. A novel
      electric interconnection strategy for high-density, small-size array elements was
      proposed. After assembly, the array transducer was tested and characterized. The
      capacitance, pulse-echo responses, and crosstalk were measured for each array
      element. The desired center frequency of ~60 MHz was achieved and the -6-dB
      bandwidth of the received signal was ~50%. At the center frequency, the crosstalk
      between adjacent 2-D array elements was about -33 dB. The techniques described
      herein can be used to build larger arrays containing smaller elements.

PMID- 24297028
TI  - Dual-frequency transducer for nonlinear contrast agent imaging.
AB  - Detection of high-order nonlinear components issued from microbubbles has emerged
      as a sensitive method for contrast agent imaging. Nevertheless, the detection of
      these high-frequency components, including the third, fourth, and fifth
      harmonics, remains challenging because of the lack of transducer sensitivity and
      bandwidth. In this context, we propose a new design of imaging transducer based
      on a simple fabrication process for high-frequency nonlinear imaging. The
      transducer is composed of two elements: the outer low-frequency (LF) element was
      centered at 4 MHz and used in transmit mode, whereas the inner high-frequency
      (HF) element centered at 14 MHz was used in receive mode. The center element was
      pad-printed using a lead zirconate titanate (PZT) paste. The outer element was
      molded using a commercial PZT, and curved porous unpoled PZT was used as backing.
      Each piezoelectric element was characterized to determine the electromechanical
      performance with thickness coupling factor around 45%. After the assembly of the
      two transducer elements, hydrophone measurements (electroacoustic responses and
      radiation patterns) were carried out and demonstrated a large bandwidth (70% at 
      3 dB) of the HF transducer. Finally, the transducer was evaluated for contrast
      agent imaging using contrast agent microbubbles. The results showed that harmonic
      components (up to the sixth harmonic) of the microbubbles were successfully
      detected. Moreover, images from a flow phantom were acquired and demonstrated the
      potential of the transducer for high-frequency nonlinear contrast imaging. 

PMID- 24297030
TI  - Numerical and experimental analysis of unidirectional meander-line coil
      electromagnetic acoustic transducers.
AB  - The elastic waves generated by traditional meander-line coil electromagnetic
      acoustic transducers (EMATs) propagate in two directions, overlapping the echo
      signals from defects with the same distances, and the defect echo signal is hard
      to distinguish from the edge-reflected signal when the EMATs are near the edge of
      a specimen. In this paper, a unidirectional EMAT with two meander-line coils is
      proposed. A finite element model is used to simulate the directivity of the
      Rayleigh and shear vertical waves generated by these EMATs. Six transducers are
      fabricated using the printed circuit technique. The unidirectional Rayleigh wave
      and shear vertical wave are tested, and the results agree well with the
      simulation.

PMID- 24297029
TI  - Flexible integration of high-imaging-resolution and high-power arrays for
      ultrasound-induced thermal strain imaging (US-TSI).
AB  - Ultrasound-induced thermal strain imaging (USTSI) for carotid artery plaque
      detection requires both high imaging resolution (<100 MUm) and sufficient US
      induced heating to elevate the tissue temperature (~1 degrees C to 3 degrees C
      within 1 to 3 cardiac cycles) to produce a noticeable change in sound speed in
      the targeted tissues. Because the optimization of both imaging and heating in a
      monolithic array design is particularly expensive and inflexible, a new
      integrated approach is presented which utilizes independent ultrasound arrays to
      meet the requirements for this particular application. This work demonstrates a
      new approach in dual-array construction. A 3-D printed manifold was built to
      support both a high-resolution 20 MHz commercial imaging array and 6 custom
      heating elements operating in the 3.5 to 4 MHz range. For the application of US
      TSI in carotid plaque characterization, the tissue target site is 20 to 30 mm
      deep, with a typical target volume of 2 mm (elevation) * 8 mm (azimuthal) * 5 mm
      (depth). The custom heating array performance was fully characterized for two
      design variants (flat and spherical apertures), and can easily deliver 30 W of
      total acoustic power to produce intensities greater than 15 W/cm(2) in the tissue
      target region.

PMID- 24297031
TI  - Spatiotemporal correlation of ultrasound contrast agent dilution curves for
      angiogenesis localization by dispersion imaging.
AB  - The major role of angiogenesis in cancer development has driven many researchers
      to investigate the prospects of noninvasive cancer imaging based on assessment of
      microvascular perfusion. The limited results so far may be caused by the complex
      and contradictory effects of angiogenesis on perfusion. Alternatively, assessment
      of ultrasound contrast agent dispersion kinetics, resulting from features such as
      density and tortuosity, has shown a promising potential to characterize
      angiogenic effects on the microvascular structure. This method, referred to as
      contrast-ultrasound dispersion imaging (CUDI), is based on contrast-enhanced
      ultrasound imaging after an intravenous contrast agent bolus injection. In this
      paper, we propose a new spatiotemporal correlation analysis to perform CUDI. We
      provide the rationale for indirect estimation of local dispersion by deriving the
      analytical relation between dispersion and the correlation coefficient among
      neighboring time-intensity curves obtained at each pixel. This robust analysis is
      inherently normalized and does not require curve-fitting. In a preliminary
      validation of the method for localization of prostate cancer, the results of this
      analysis show superior cancer localization performance (receiver operating
      characteristic curve area of 0.89) compared with those of previously reported
      CUDI implementations and perfusion estimation methods. 

PMID- 24297032
TI  - Beam-domain eigenspace-based minimum variance beamformer for medical ultrasound
      imaging.
AB  - The eigenspace-based minimum variance (ESBMV) beamformer can provide good imaging
      resolution and contrast; however, the performance is achieved at the cost of high
      computational complexity. In adaptive array processing, the beamspace method is
      an efficient way to lower the computational complexity. In this paper, we combine
      the beamspace method with the ESBMV beamformer and propose a beamdomain ESBMV
      beamformer. We demonstrate the feasibility of introducing the beamspace into the
      ESBMV beamformer and propose an effective method of forming the transform matrix
      based on the spatial spectrum of the array signals. We also illustrate the
      performance of the proposed beamformer when resolving point scatterers and a cyst
      phantom with both simulated and experimental data. The results show that the
      proposed method can achieve performance comparable to the ESBMV beamformer within
      much shorter time. 

PMID- 24297033
TI  - Acoustic waves in a structure containing two piezoelectric plates separated by an
      air (vacuum) gap.
AB  - This paper presents experimental results for the characteristics of acoustic
      waves propagating in a structure containing two parallel piezoelectric plates (I
      and II) separated by an air gap. Plate I, made of Y-X lithium niobate, contained
      two interdigital transducers that excited and received an acoustic wave with
      shear-horizontal polarization. Piezoelectric plate II, made of lithium niobate,
      was placed above and between the transducers, separated by a fixed gap. For its
      certain orientation, the amplitude-frequency characteristic showed sharply
      defined resonant attenuation peaks, which were situated at an equidistant
      separation from each other. The depth of the peaks was observed to decrease with
      a wider gap between the plates. It has been stated that these peaks are
      associated with the resonant reflections of a slot acoustic wave across the width
      of plate II. Experimentally determined phase velocities and electromechanical
      coupling coefficient for the slot wave in the structure under study are in a good
      agreement with theoretical values for various crystallographic orientations of
      plate II. A comparison between the experimental and theoretical results has
      allowed us to state two conditions for the slot wave to exist. The structures
      described may be employed for noncontact excitation of acoustic waves in the
      plates and for the development of various liquid, gas, and temperature sensors. 

PMID- 24297034
TI  - Multi-line transmission in medical imaging using the second-harmonic signal.
AB  - The emergence of three-dimensional imaging in the field of medical ultrasound
      imaging has greatly increased the number of transmissions needed to insonify a
      whole volume. With a large number of transmissions comes a low image frame rate.
      When using classical transmission techniques, as in two-dimensional imaging, the
      frame rate becomes unacceptably low, prompting the use of alternative
      transmission patterns that require less time. One alternative is to use a multi
      line transmission (MLT) technique which consists of transmitting several pulses
      simultaneously in different directions. Perturbations appear when acquiring and
      beamforming the signal in the direction of one pulse because of the pulses sent
      in other directions. The edge waves from the pulses transmitted in a different
      direction add to the signal transmitted in the direction of interest, resulting
      in artifacts in the final image. Taking advantage of the nonlinear propagation of
      sound in tissue, the second-harmonic signal can be used with the MLT technique.
      The image obtained using the second-harmonic signal, compared with an image
      obtained using the fundamental signal, should have reduced artifacts coming from
      other pulses transmitted simultaneously. Simulations, backed up by experiments
      imaging a wire target and an in vivo left ventricle, confirm that the hypothesis
      is valid. In the studied case, the perturbations appear as an increase in the
      signal level around the main echo of a point scatterer. When using the
      fundamental signal, the measured amplitude level of the perturbations was
      approximately -40 dB compared with the maximum signal amplitude (-27 dB in vivo),
      whereas it was around -60 dB (-45 dB in vivo) for the second-harmonic signal. The
      MLT technique encounters limitations in the very near field where the pulses
      overlap and the perturbation level also increases for images with strong speckle
      and low contrast. 

PMID- 24297035
TI  - Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer.
AB  - To elucidate the molecular mechanisms underlying the insufficient sensitivity in
      the detection of hepatocellular carcinoma (HCC) by [18F] 2-fluoro-2-deoxy-D
      glucose positron emission tomography (FDG-PET), the characteristics of glucose
      metabolism-related protein expression in HCC were examined in liver metastasis
      from colorectal cancer (Meta). Thirty-four patients (14 Meta and 20 HCC) who
      underwent FDG-PET and hepatectomy were studied. The relationships between the
      maximum standardized uptake value (SUV) in tumors and the mRNA expression of
      glucose metabolism-related proteins [hexokinase (HK), glucose transporter 1
      (GLUT1), and glucose-6-phosphatase (G6Pase)] and proliferating cell nuclear
      antigen (PCNA) were examined in snap-frozen specimens with quantitative PCR.
      Tumor detection rates were lower in HCC (15/20) compared to Meta (13/14)
      patients. HK and GLUT1 expression was lower and G6Pase expression was higher in
      HCC compared to Meta. In particular, GLUT1 overexpression was 92-fold in Meta and
      11-fold in HCC compared to the surrounding liver. The SUV correlated with GLUT1
      and PCNA expression in HCC, but not Meta patients. Of note, four cases of poorly
      differentiated (P/D) HCC compared to moderately differentiated (M/D) HCC produced
      completely different results for FDG uptake (SUV, 14.4 vs. 4.0) and mRNA
      expression (G6Pase expression, 0.007 vs. 1.5). Variations in the expression of
      glucose metabolism-related enzymes between HCC and Meta patients are attributed
      to origin or degree of differentiation. Low FDG uptake in M/D HCC reflected low
      GLUT1 and high G6Pase expression, while high FDG accumulation in P/D HCC could
      reflect increased GLUT1 and decreased G6Pase expression. These results may
      explain why M/D HCC is not detected as sensitively by FDG-PET.

PMID- 24297036
TI  - Evidence of the two surface states of (Bi0.53Sb0.47)2Te3 films grown by van der
      Waals epitaxy.
AB  - The discovery of topological insulators (TIs) has led to numerous exciting
      opportunities for studying topological states of quantum physics and for
      exploring spintronic applications due to the new physics arising from their
      robust metallic surface states. Here, we report the high-quality topological
      insulator (BixSb1-x)2Te3 thin films using a single van der Waals GaSe buffer
      layer. As a result, ultra-low surface carrier density of 1.3 * 10(12) cm(-2) and
      a high Hall mobility of 3100 cm(2)/Vs have been achieved for (Bi0.53Sb0.47)2Te3.
      The high-quality films enable us to observe quantum oscillations associated with
      the top and bottom surface states and to manipulate the Dirac electrons and bulk
      holes' conduction properties. The observation of the two surface states may lead
      to a path towards the implementation of TIs in spintronics. 

PMID- 24297037
TI  - The impact of visceral obesity on surgical outcomes of laparoscopic surgery for
      colon cancer.
AB  - PURPOSE: Although obesity is considered as a risk factor for postoperative
      morbidity in abdominal surgery, its effect on the outcomes of laparoscopic
      assisted colectomy (LAC) is still unclear. The technical difficulty and risk
      factor for postoperative complication in LAC are thought to be influenced by
      visceral obesity. The aim of this prospective study was to evaluate the impact of
      visceral fat on the surgical outcomes of LAC. METHODS: Between April 2005 and
      December 2010, consecutive patients with preoperatively diagnosed colon cancer,
      excluding medium and low rectal cancer, who underwent LAC, were enrolled. Their
      visceral fat area (VFA) and body mass index (BMI) were prospectively collected.
      The VFA was assessed by Fat Scan software. The patients were classified into two
      groups as follows: VFA nonobese with VFA <100 cm(2) (VNO) and VFA obese with VFA
      ?100 cm(2) (VO). The predictive factors for surgical complications of LAC were
      evaluated by univariate and logistic regression analyses. RESULTS: A total of 338
      consecutive patients were enrolled in this study. Of the 338 patients, 194 (57.4
      %) and 138 (42.6 %) were classified into the VNO and VO groups, respectively.
      Logistic regression analysis showed that high BMI (?25 kg/m(2)) and VO
      independently predicted the incidence of overall postoperative complications (p =
      0.040 and 0.007, respectively). VO was more highly related to the incidence of
      overall postoperative complications, anastomotic leakage (p = 0.021), and
      surgical site infection (SSI) (p = 0.013) than high BMI. CONCLUSIONS: VFA is a
      more useful parameter than BMI in predicting surgical outcomes after LAC.

PMID- 24297038
TI  - Carbon dioxide insufflation during colorectal endoscopic submucosal dissection
      for patients with obstructive ventilatory disturbance.
AB  - PURPOSE: Carbon dioxide (CO(2)) insufflation reduces abdominal pain and
      discomfort after endoscopic procedures; however, there is no previous study
      focusing the safety of CO(2) insufflation for patients with obstructive
      ventilatory disturbance. Here, we investigated the safety of CO(2) insufflation
      during colorectal endoscopic submucosal dissection (ESD) for patients with
      obstructive disturbance. METHODS: Between January 2010 and January 2013,
      colorectal ESD was performed using CO(2) insufflation for 385 consecutive
      patients. End-tidal CO(2) (EtCO(2)) and transcutaneous oxygen saturation (SpO(2))
      were consecutively measured from the time before insertion of the colonoscope to
      the end of ESD. Patients were monitored by two nurses during the procedure and
      controlled for clinical symptoms of hypercapnia such as apnea or a depressed
      level of consciousness. According to their respiratory function, patients were
      stratified into a normal group and an obstructive disturbance group. We
      retrospectively compared EtCO(2) and SpO(2) during the procedures and the
      incidence of symptoms related to CO(2) retention between the two groups. RESULTS:
      The obstructive disturbance group consisted of 77 patients. There were similar
      changes of EtCO(2) in the obstructive disturbance group and normal group and no
      significant rise in EtCO(2). The maximum EtCO(2) level in any patient was <60
      mmHg. In the obstructive disturbance group, there were no symptoms associated
      with CO(2) retention. There were no significant differences in the median SpO(2)
      between both groups and no prolonged drop of SpO(2). CONCLUSIONS: CO(2)
      insufflation during colorectal ESD is safe for patients with obstructive
      ventilatory disturbance.

PMID- 24297040
TI  - Continuous flow real-time PCR device using multi-channel fluorescence excitation
      and detection.
AB  - High throughput automation is greatly enhanced using techniques that employ
      conveyor belt strategies with un-interrupted streams of flow. We have developed a
      'conveyor belt' analog for high throughput real-time quantitative Polymerase
      Chain Reaction (qPCR) using droplet emulsion technology. We developed a low
      power, portable device that employs LED and fiber optic fluorescence excitation
      in conjunction with a continuous flow thermal cycler to achieve multi-channel
      fluorescence detection for real-time fluorescence measurements. Continuously
      streaming fluid plugs or droplets pass through tubing wrapped around a two
      temperature zone thermal block with each wrap of tubing fluorescently coupled to
      a 64-channel multi-anode PMT. This work demonstrates real-time qPCR of 0.1-10 MUL
      droplets or fluid plugs over a range of 7 orders of magnitude concentration from
      1 * 10(1) to 1 * 10(7). The real-time qPCR analysis allows dynamic range
      quantification as high as 1 * 10(7) copies per 10 MUL reaction, with PCR
      efficiencies within the range of 90-110% based on serial dilution assays and a
      limit of detection of 10 copies per rxn. The combined functionality of continuous
      flow, low power thermal cycling, high throughput sample processing, and real-time
      qPCR improves the rates at which biological or environmental samples can be
      continuously sampled and analyzed. 

PMID- 24297041
TI  - Differential association of the Na+/H+ Exchanger Regulatory Factor (NHERF) family
      of adaptor proteins with the raft- and the non-raft brush border membrane
      fractions of NHE3.
AB  - BACKGROUND/AIMS: Trafficking, brush border membrane (BBM) retention, and signal
      specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+
      Exchanger Regulatory Factor (NHERF) family of PDZ-adaptor proteins, which enable
      the formation of multiprotein complexes. It is unclear, however, what determines
      signal specificity of these NHERFs. Thus, we studied the association of NHE3,
      NHERF1 (EBP50), NHERF2 (E3KARP), and NHERF3 (PDZK1) with lipid rafts in murine
      small intestinal BBM. METHODS: Detergent resistant membranes ("lipid rafts") were
      isolated by floatation of Triton X-incubated small intestinal BBM from a variety
      of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3
      activity was measured fluorometrically in BCECF-loaded microdissected villi, or
      by assessment of CO2/HCO3(-) mediated increase in fluid absorption in perfused
      jejunal loops of anethetized mice. RESULTS: NHE3 was found to partially associate
      with lipid rafts in the native BBM, and NHE3 raft association had an impact on
      NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were
      differentially distributed to rafts and non-rafts, with NHERF2 being most raft
      associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced
      the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase
      deficient mice, which have altered membrane lipid as well as lipid raft
      composition, allowed us to test the validity of the lipid raft concept in vivo.
      CONCLUSIONS: The differential association of the NHERFs with the raft-associated
      and the non-raft fraction of NHE3 in the brush border membrane is one component
      of the differential and signal-specific NHE3 regulation by the different NHERFs.

PMID- 24297043
TI  - Spatial cluster analysis of nanoscopically mapped serotonin receptors for
      classification of fixed brain tissue.
AB  - We present a cluster spatial analysis method using nanoscopic dSTORM images to
      determine changes in protein cluster distributions within brain tissue. Such
      methods are suitable to investigate human brain tissue and will help to achieve a
      deeper understanding of brain disease along with aiding drug development. Human
      brain tissue samples are usually treated postmortem via standard fixation
      protocols, which are established in clinical laboratories. Therefore, our
      localization microscopy-based method was adapted to characterize protein density
      and protein cluster localization in samples fixed using different protocols
      followed by common fluorescent immunohistochemistry techniques. The localization
      microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a
      two-dimensional image of a brain tissue slice. These nanoscopically mapped
      proteins can be confined to clusters by applying the proposed statistical spatial
      analysis. Selected features of such clusters were subsequently used to
      characterize and classify the tissue. Samples were obtained from different types
      of patients, fixed with different preparation methods, and finally stored in a
      human tissue bank. To verify the proposed method, samples of a cryopreserved
      healthy brain have been compared with epitope-retrieved and paraffin-fixed
      tissues. Furthermore, samples of healthy brain tissues were compared with data
      obtained from patients suffering from mental illnesses (e.g., major depressive
      disorder). Our work demonstrates the applicability of localization microscopy and
      image analysis methods for comparison and classification of human brain tissues
      at a nanoscopic level. Furthermore, the presented workflow marks a unique
      technological advance in the characterization of protein distributions in brain
      tissue sections.

PMID- 24297042
TI  - Vitamin D receptor gene polymorphisms in breast and renal cancer: current state
      and future approaches (review).
AB  - Cancer is a major health problem and cause of death worldwide that accounted for
      7.6 million deaths in 2008, which is projected to continue rising with an
      estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the
      leading cause of cancer-based death among women around the world and its
      incidence is increasing annually with a similar tendency. In contrast, renal cell
      carcinoma accounts for only 3% of total human malignancies but it is still the
      most common type of urological cancer with a high prevalence in elderly men (>60
      years of age). There are several factors linked with the development of renal
      cell cancer only, while others are connected only with breast cancer. Genetic
      risk factors and smoking are the factors which contribute to carcinogenesis in
      general. Some evidence exists indicating that vitamin D receptor (VDR) gene
      polymorphisms are associated with both breast and renal cancer; therefore, we put
      forward the hypothesis that polymorphisms in the VDR gene may influence both the
      occurrence risks of these cancers and their prognosis. However, the relationship
      between VDR polymorphisms and these two specific cancers remains a controversial
      hypothesis, and consequently needs further confirmation via clinical research
      together with genetic investigations. Here, we aimed to assess the correlation
      between the different alleles of VDR gene polymorphisms and renal cell cancer and
      breast cancer risks separately through a systematic review of the present
      literature. In contrast, this analysis has revealed that some VDR gene
      polymorphisms, such as: Bsm1, poly(A), Taq1, Apa1, are to some extent associated
      with breast cancer risk. Other polymorphisms were found to be significantly
      associated with renal cell cancer. Namely, they were Fok1, Bsm1, Taq1 and Apa1,
      which encode proteins participating mainly in proliferation, apoptosis and cell
      cycle regulation. However, data concerning renal cancer are not sufficient to
      firmly establish the VDR gene polymorphism association.

PMID- 24297044
TI  - Identification and in vitro characterization of phage-displayed VHHs targeting
      VEGF.
AB  - Vascular endothelial growth factor (VEGF) is a potential target for cancer
      treatment because of its role in angiogenesis and its overexpression in most
      human cancers. Currently, anti-VEGF antibodies have been shown to be promising
      tools for therapeutic applications. However, large size, poor tumor penetration,
      immunogenicity, and production in cost- and labor-intensive conditions are major
      drawbacks of such agents. The antigen-binding regions of camelid single-chain
      antibodies (VHHs), due to their unique biophysical characteristics, offer an
      alternative to conventional antibodies for tumor-targeting purposes. The present
      study was undertaken to generate and characterize anti-VEGF VHHs from an immune
      VHH library using phage display. Four rounds of panning were performed, and
      selected VHHs were characterized using various immunological techniques.
      Assessment of the antigenic profile of VHHs was done using competition enzyme
      linked immunosorbent assay (ELISA). Selected VHHs reacted strongly to VEGF in
      indirect ELISA and cross-reactivity ELISA tests. The binding affinity of three
      VHHs, ZFR-1, ZFR-2, and ZFR-5, ranged from 2.5 to 80 nM, and among them, ZFR-5,
      which was selected for proliferation assay, significantly inhibited the
      endothelial cell growth in a dose-dependent manner. Taken together, our results
      indicate that ZFR-5 and other VHHs may be promising tools in cancer research and
      treatment. 

PMID- 24297045
TI  - Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor
      recovery after spinal cord injury: a systematic review and meta-analysis.
AB  - IMPORTANCE: Blockade of small GTPase-RhoA signaling pathway is considered a
      candidate translational strategy to improve functional outcome after spinal cord
      injury (SCI) in humans. Pooling preclinical evidence by orthodox meta-analysis is
      confounded by missing data (publication bias). OBJECTIVE: To conduct a systematic
      review and meta-analysis of RhoA/Rho-associated coiled-coil containing protein
      kinase (ROCK) blocking approaches to (1) analyze the impact of bias that may lead
      to inflated effect sizes and (2) determine the normalized effect size of
      functional locomotor recovery after experimental thoracic SCI. EVIDENCE REVIEW:
      We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand
      searched related references. Studies were selected if they reported the effect of
      RhoA/ROCK inhibitors (C3-exoenzmye, fasudil, Y-27632, ibuprofen, siRhoA, and p21)
      in experimental spinal cord hemisection, contusion, or transection on locomotor
      recovery measured by the Basso, Beattie, and Bresnahan score or the Basso Mouse
      Scale for Locomotion. Two investigators independently assessed the identified
      studies. Details of individual study characteristics from each publication were
      extracted and effect sizes pooled using a random effects model. We assessed risk
      for bias using a 9-point-item quality checklist and calculated publication bias
      with Egger regression and the trim and fill method. A stratified meta-analysis
      was used to assess the impact of study characteristics on locomotor recovery.
      FINDINGS: Thirty studies (725 animals) were identified. RhoA/ROCK inhibition was
      found to improve locomotor outcome by 21% (95% CI, 16.0-26.6). Assessment of
      publication bias by the trim and fill method suggested that 30% of experiments
      remain unpublished. Inclusion of these theoretical missing studies suggested a
      27% overestimation of efficacy, reducing the overall efficacy to a 15%
      improvement in locomotor recovery. Low study quality was associated with larger
      estimates of neurobehavioral outcome. CONCLUSIONS AND RELEVANCE: Taking into
      account publication bias, RhoA/ROCK inhibition improves functional outcome in
      experimental SCI by 15%. This is a plausible strategy for the pharmacological
      augmentation of neurorehabilitation after human SCI. These findings support the
      necessity of a systematic analysis to identify preclinical bias before embarking
      on a clinical trial.

PMID- 24297046
TI  - A recyclable and base-free method for the synthesis of 3-iodothiophenes by the
      iodoheterocyclisation of 1-mercapto-3-alkyn-2-ols in ionic liquids.
AB  - The first example of an iodocyclisation reaction made recyclable by the use of an
      ionic liquid as the reaction medium is reported. Readily available 1-mercapto-3
      alkyn-2-ols were smoothly converted into the corresponding 3-iodothiophenes (50
      81% yields, 10 examples) when allowed to react with iodine (1-2 equiv.) in a
      proper ionic liquid, such as 1-ethyl-3-methylimidazolium ethyl sulfate
      (EmimEtSO4), as the solvent under mild reaction conditions (25  degrees C) and in
      the absence of an external base. The reaction medium can be recycled several
      times without significantly affecting the reaction outcome. Theoretical
      calculations have also been performed to investigate the role of the ionic liquid
      anion in the reaction. 

PMID- 24297047
TI  - Angiostatin inhibits activation and migration of neutrophils.
AB  - There is a critical need to identify molecules that modulate the biology of
      neutrophils because activated neutrophils, though necessary for host defense,
      cause exuberant tissue damage through production of reactive oxygen species and
      increased lifespan. Angiostatin, an endogenous anti-angiogenic cleavage product
      of plasminogen, binds to integrin alphavbeta3, ATP synthase and angiomotin and
      its expression is increased in inflammatory conditions. We test the hypothesis
      that angiostatin inhibits neutrophil activation, induces apoptosis and blocks
      recruitment in vivo and in vitro. The data show immuno-reactivity for
      plasminogen/angiostatin in resting neutrophils. Angiostatin conjugated to FITC
      revealed that angiostatin was endocytozed by activated mouse and human
      neutrophils in a lipid raft-dependent fashion. Co-immunoprecipitation of human
      neutrophil lysates, confocal microscopy of isolated mouse and human neutrophils
      and functional blocking experiments showed that angiostatin complexes with
      flotillin-1 along with integrin alphavbeta3 and ATP synthase. Angiostatin
      inhibited fMLP-induced neutrophil polarization, as well as caused inhibition of
      hsp-27 phosphorylation and stabilization of microtubules. Angiostatin treatment,
      before or after LPS-induced neutrophil activation, inhibited phosphorylation of
      p38 and p44/42 MAPKs, abolished reactive oxygen species production and released
      the neutrophils from suppressed apoptosis, as indicated by expression of
      activated caspase-3 and morphological evidence of apoptosis. Finally, intravital
      microscopy and myeloperoxidase assay showed inhibition of neutrophil recruitment
      in post-capillary venules of TNFalpha-treated cremaster muscle in mouse. These in
      vitro and in vivo data demonstrate angiostatin as a broad deactivator and
      silencer of neutrophils and an inhibitor of their migration. These data
      potentially open new avenues for the development of anti-inflammatory drugs. 

PMID- 24297048
TI  - Repression of choroidal neovascularization through actin cytoskeleton pathways by
      microRNA-24.
AB  - Actin cytoskeleton is critical for cell motility and division, both of which are
      important for angiogenesis. MicroRNAs (miRNA/miR) are emerging as pivotal
      modulators of vascular development and disease. How miRNAs regulate actin
      cytoskeleton dynamics in endothelial cells (EC) and neovascularization is still
      unclear. Here, we report that miR-24 regulates actin dynamics in ECs through
      targeting multiple members downstream of Rho signaling, including Pak4, Limk2,
      and Diaph1 proteins. Overexpression of miR-24 in ECs blocks stress fiber and
      lamellipodia formation, represses EC migration, proliferation, and tube formation
      in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Moreover,
      subretinal delivery of miR-24 mimics represses laser-induced choroidal
      neovascularization (CNV) in vivo. Mechanistically, knockdown of miR-24 target
      protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in
      vitro, mimicking miR-24 overexpression phenotype in angiogenesis, while
      overexpression of LIMK2 and PAK4 by adenoviruses partially rescued the tube
      formation defects in miR-24 overexpressing ECs. Taken together, these findings
      suggest that miR-24 represses angiogenesis by simultaneously regulating multiple
      components in the actin cytoskeleton pathways. Manipulation of actin cytoskeleton
      pathways by miR-24 may represent an attractive therapeutic solution for the
      treatment of wet age-related macular degeneration (AMD) and other vascular
      diseases. 

PMID- 24297052
TI  - Hydrogen defects in tetragonal ZrO2 studied using density functional theory.
AB  - In the energy-structure paradigm, we analyzed the defects that can arise in
      tetragonal zirconium oxide (T-ZrO2) involving the hydrogen atom or the hydrogen
      molecule using density functional theory. Our results indicate that the dominant
      hydrogen defect under reducing conditions is H(.)(0), a complex formed between
      the hydride ion and a doubly charged oxygen vacancy. This result is consistent
      with the experimental observation that under reducing conditions, the solubility
      of hydrogen is proportional to the degree of hypostoichiometry of T-ZrO2. Under
      oxidizing conditions we found three different hydrogen defects, each
      predominating in a specific range of the chemical potential of electrons.
      Starting from the valence band top toward the conduction band bottom, these
      defects are the interstitial proton, H(.)(i), a complex formed between two
      hydrogen species and a zirconium vacancy with a net effective charge of (2-),
      (2H)"(Zr), and finally a complex similar to the latter but with a net effective
      charge of (4-), (H(2))'''(Zr). In (2H)"(Zr)the two hydrogens exist in the form of
      hydroxyl groups, while in (H(2))" " (Zr) they exist in the form of a hydrogen
      molecule. In addition, we found that up to three hydrogen species can favorably
      accumulate in a zirconium vacancy under oxidizing conditions. The clustering of
      hydrogen in cation vacancies can be a precursor for the deleterious effects of
      hydrogen on the mechanical properties and stability of metal oxides, in analogy
      with hydrogen embrittlement in metals. Finally we observed a red-shift and a blue
      shift for the vibrational frequencies of all the hydroxyl groups and all the
      hydrogen molecules, respectively, in T-ZrO2 when compared to the gas phase
      frequencies. This is an important characteristic for guiding future experimental
      efforts to detect and identify hydrogen defects in T-ZrO2. The insights presented
      in this work advance our predictive understanding of the degradation behavior of
      T-ZrO2 as a corrosion resistant passive layer, as a gate dielectric and in
      biomedical applications.

PMID- 24297049
TI  - Adoptive T-cell transfer and chemotherapy in the first-line treatment of
      metastatic and/or locally recurrent nasopharyngeal carcinoma.
AB  - The outcomes for patients with metastatic or locally recurrent Epstein-Barr virus
      (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy
      with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical
      efficacy, but it has never been evaluated in the first-line treatment setting in
      combination with chemotherapy. To evaluate the safety and efficacy of a
      chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase
      2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC)
      followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and
      35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4%
      with 3 complete responses and 22 partial responses. With a median follow up of
      29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%,
      respectively. Five patients did not require further chemotherapy for more than 34
      months since initiation of CTL. Infusion of CTL products containing T cells
      specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95%
      confidence interval: 0.14-0.84; P = 0.014). Our study achieved one of the best
      survival outcomes in patients with advanced NPC, setting the stage for a future
      randomized study of chemotherapy with and without EBV-CTL. 

PMID- 24297051
TI  - Knockdown of Slit2 promotes growth and motility in gastric cancer cells via
      activation of AKT/beta-catenin.
AB  - We previously showed that Slit2 was highly expressed in gastric cancer tissues
      that exhibit less advanced clinicopathological features, suggesting a tumor
      suppressor role for Slit2. In the present study, we investigated the effects of
      Slit2 knockdown on gastric cancer cells. Slit2-specific shRNAs were used to
      generate Slit2-knockdown SGC-7901 gastric cancer cells. Cell proliferation assay,
      Annexin V/PI double staining and cell cycle analysis were used to investigate the
      role of Slit2 knockdown in cell growth. Wound-healing and in vitro
      migration/invasion assays were performed. Subcutaneous tumor formation and
      peritoneal spreading in nude mice were employed to examine the in vivo effects of
      Slit2 knockdown. Cell signaling changes induced by Slit2 knockdown were analyzed
      by immunoblotting. Slit2 knockdown increased gastric cancer cell growth in
      monolayer and soft agar/Matrigel 3D culture. Slit2 knockdown inhibited apoptosis
      but did not alter cell cycle progression. Slit2-knockdown cells formed larger
      tumors and produced more peritoneal metastatic nodules in nude mice. Slit2
      knockdown increased AKT phosphorylation, activated anti-apoptotic signaling,
      suppressed GSK3beta activity and induced beta-catenin activation. Blocking the
      effects of PI3K/AKT using pharmacological inhibitors abolished the ability of
      Slit2 knockdown to induce apoptosis resistance and cell migration/invasion. These
      results indicate that Slit2 knockdown promotes gastric cancer growth and
      metastasis through activation of the AKT/beta-catenin-mediated signaling pathway.

PMID- 24297053
TI  - Claude Bernard and his revelations in physiology.
AB  - It was in Saint-Julien near Villefranche that Claude Bernard was born on 12 July
      1813. About 20 years later he moved to Paris to become a dramatist but was
      directed into the study of medicine, the service at the Hotel Dieu of Magendie
      that led him to the College de France. He entered Magendie's laboratory as a
      voluntary assistant and within a year became official preparateur. His early work
      on the chorda tympani and his MD thesis on gastric juice in 1843 set him on his
      lifelong discoveries in physiology. The central role of hepatic glycogenesis in
      the formation of sugar in animals was established around 1850, and he proceeded
      to show that section of the cervical fibres of the sympathetic chain led to
      congestion and increased temperature on that side of the face-resulting from
      paralysis of the vasomotor nerves. And there were vasodilator as well as
      vasoconstrictor fibres. After the salivary glands, the pancreas caught his
      attention and he discovered its ability to emulsify fatty material. Toxic and
      therapeutic substances were analysed: carbon monoxide paralyses carriage of
      oxygen by taking its place on haemoglobin; and curare abolishes voluntary
      movement by paralysis at the motor end-plate. But Bernard was above all a general
      physiologist, exemplified in 1872 and 1873 in his Lectures on the phenomena of
      life common to animals and plants, summarised in the apercu 'the constancy of the
      internal environment is the condition of the free and independent life'. Claude
      Bernard died on Sunday 10 February 1878 in Paris.

PMID- 24297054
TI  - Rescue therapy with cyclosporine or infliximab is not associated with an
      increased risk for postoperative complications in patients hospitalized for
      severe steroid-refractory ulcerative colitis.
AB  - BACKGROUND: Cyclosporine and infliximab (IFX) are effective medical therapies for
      inducing remission in patients with steroid-refractory ulcerative colitis (UC).
      Patients with acute severe disease who do not respond to these therapies require
      colectomy, however, the risk of postoperative complications in such patients is
      not known. Analyzing patients with acute severe UC, we compared the incidence of
      postoperative complications in patients who failed rescue therapy with
      cyclosporine or IFX with that in patients who received intravenous (IV)
      corticosteroids alone. METHODS: We performed a retrospective cohort study of UC
      patients who underwent colectomy after inpatient treatment with cyclosporine plus
      IV corticosteroids (CsA+IVS), infliximab plus IV corticosteroids (IFX+IVS), or IV
      corticosteroids alone (IVS) at the University of Chicago Hospitals from October
      1, 2006 to October 1, 2012. Primary endpoints were infectious, noninfectious, and
      total complications occurring within 30 days of colectomy. RESULTS: Of 78
      patients, 19 were treated with CsA+IVS, 24 with IFX+IVS, 4 with both CsA and
      IFX+IVS, and 31 with IVS alone. Patients treated with rescue therapy plus IVS had
      no difference in total postoperative complications compared with those receiving
      IVS alone (CsA+IVS: relative risk (RR) = 0.63, 95% confidence interval (CI), 0.33
      1.23; IFX+IVS: RR = 0.65, 95% CI, 0.36-1.17). There remained no difference in
      postoperative complications between the rescue therapy and IVS alone groups when
      subcategorizing overall complications into infectious (CsA+IVS: RR = 0.54, 95%
      CI, 0.17-1.76; IFX+IVS: RR = 0.86, 95% CI, 0.36-2.09) and noninfectious (CsA+IVS:
      RR = 0.88, 95% CI, 0.43-1.80; IFX+IVS: RR = 0.40, 95% CI, 0.15-1.07) causes.
      CONCLUSIONS: Cyclosporine and IFX are not associated with an increased risk for
      postoperative complications in patients hospitalized for severe UC refractory to
      corticosteroids.

PMID- 24297056
TI  - Factors associated with physical and cognitive fatigue in patients with Crohn's
      disease: a cross-sectional and longitudinal study.
AB  - BACKGROUND: Fatigue commonly impairs quality of life in patients with Crohn's
      disease (CD). This study aimed to evaluate the prevalence and severity of fatigue
      in CD (compared with ulcerative colitis [UC] and healthy controls) and to
      identify potentially modifiable factors associated with global, physical, and
      cognitive dimensions of fatigue. METHODS: Clinic attendees with confirmed CD or
      UC and healthy volunteers were surveyed on fatigue (Fatigue Impact Scale, FIS),
      psychological comorbidity, sleep quality, medication, and other clinical
      information. A CD subgroup also completed a similar follow-up survey. RESULTS: In
      379 responders (181 CD, 113 UC, and 85 controls), global, physical, and cognitive
      FIS scores were highest in CD followed by UC and controls (P < 0.01), with a
      prevalence of global fatigue (total FIS >= 40) in 57% of CD patients. On
      multivariate analysis, concurrently active disease, poor sleep quality, and
      mental illness were significantly associated with all the 3 fatigue dimensions:
      regular vitamin B group supplementation was inversely associated with physical
      fatigue in the CD cohort and those of older age or with previous resection(s) (P
      = 0.05) were independently associated with cognitive fatigue only. Longitudinally
      in CD, fatigue scores remained constant between original and follow-up surveys
      (mean change in total FIS score +0.9; 95% confidence interval, -4.6 to 6.3).
      Factors independently associated with improved physical fatigue between surveys
      included avoidance of corticosteroids and establishment of regular exercise and
      with improved cognitive fatigue included cessation of immunomodulator therapy.
      CONCLUSIONS: Fatigue is highly prevalent and more severe in CD. Anticipated and
      novel associations with improvement of physical and/or cognitive fatigue were
      identified, offering clues to potential therapeutic approaches to ameliorating
      fatigue for clinical evaluation.

PMID- 24297055
TI  - NOD2 expression is regulated by microRNAs in colonic epithelial HCT116 cells.
AB  - BACKGROUND: Crohn's disease (CD) is associated with defective sensing of
      pathogens in genetically susceptible individuals. Nucleotide-binding
      oligomerization domain containing 2 (NOD2) mutations in coding regions are
      strongly linked to CD pathogenesis. Our laboratory has reported that microRNAs
      (miRNAs) are differentially expressed in CD. However, miRNA regulation of NOD2
      remains unknown. This study was designed to determine whether miRNAs regulate
      NOD2 expression as well as downstream nuclear factor kappaB activation and
      inflammatory responses in colonic epithelial HCT116 cells. METHODS: NOD2 and
      miRNA expression in stimulated HCT116 cells were assessed by quantitative reverse
      transcription-polymerase chain reaction. Regulation of NOD2 expression by miRNAs
      was determined by luciferase reporter construct assays and transfection of
      specific miRNA mimics. Regulation of NOD2 signaling and immune response by miRNAs
      was assessed by transfection of mimics followed by muramyl dipeptide stimulation.
      RESULTS: Muramyl dipeptide-induced increases in NOD2, interleukin-8, and CXCL3
      expression were inversely associated with miRNA expression. Overexpression of miR
      192, miR-495, miR-512, and miR-671 suppressed NOD2 expression, muramyl dipeptide
      mediated NF-kappaB activation, and messenger RNA expressions of interleukin-8 and
      CXCL3 in HCT116 cells. A single-nucleotide polymorphism (rs3135500) located in
      the NOD2 3'-untranslated region significantly reduced miR-192 effects on NOD2
      gene expression. CONCLUSIONS: To our knowledge, this is the first report
      demonstrating that miRNAs regulate NOD2 and its signaling pathway. Four miRNAs
      downregulate NOD2 expression, suppress NF-kappaB activity, and inhibit
      interleukin-8 and CXCL3 messenger RNA expression. Treatment of CD with miRNAs may
      represent a potential anti-inflammatory therapeutic strategy in CD patients with
      and without NOD2 gene mutations.

PMID- 24297057
TI  - Localized surface plasmon resonance based nanobiosensor for biomarker detection
      of invasive cancer cells.
AB  - In this study, we describe the development of a cancer biomarker-sensitive
      nanobiosensor based on localized surface plasmon resonance that enables
      recognition for proteolytic activity of membrane type 1 matrix metalloproteinase
      (MT1-MMP) anchored on invasive cancer cells. First of all, we prepared biomarker
      detectable substrate based on gold nanorods (GNRs) using nanoparticle adsorption
      method. The sensitivity of the sensing chip was confirmed using various solvents
      that have different refractive indexes. Subsequently, MT1-MMP-specific cleavable
      peptide was conjugated onto the surface of GNRs, and molecular sensing about
      proteolytic activity was conducted using MT1-MMP and cell lysates. Collectively,
      we developed a biomarker detectable sensor, which allows for the effective
      detection of proteolytic activity about MT1-MMP extracted from invasive cancer
      cells.

PMID- 24297058
TI  - Aptamer-conjugated gold nanorod for photothermal ablation of epidermal growth
      factor receptor-overexpressed epithelial cancer.
AB  - Biomarker-specific photothermal nanoparticles that can efficiently sense markers
      that are overexpressed in distinguished adenocarcinomas have attracted much
      interest in an aspect of efficacy increase of cancer treatment. We demonstrated a
      promising prospect of a smart photothermal therapy agent employing anti-epidermal
      growth factor receptor aptamer (AptEGFR)-conjugated polyethylene glycol (PEG)
      layted gold nanorods (AptEGFR-PGNRs). The cetyltrimethylammonium bromide bilayer
      on GNRs was replaced with heterobifunctional PEG (COOH-PEG-SH) not only to serve
      as a biocompatible stabilizer and but also to conjugate AptEGFR. Subsequently, to
      direct photothermal therapy agent toward epithelial cancer cells, the
      carboxylated PEGylated GNRs (PGNRs) were further functionalized with AptEGFR
      using carbodiimide chemistry. Then, to assess the potential as biomarker-specific
      photothermal therapy agent of synthesized AptEGFR-PGNRs, the optical properties,
      biocompatibility, colloidal stability, binding affinity, and epicellial cancer
      cell killing efficacy in vitro/in vivo under near-infrared laser irradiation were
      investigated. As a result, AptEGFR-PGNRs exhibit excellent tumor targeting
      ability and feasibility of effective photothermal ablation cancer therapy.

PMID- 24297059
TI  - Aptamer-based single-molecule imaging of insulin receptors in living cells.
AB  - We present a single-molecule imaging platform that quantitatively explores the
      spatiotemporal dynamics of individual insulin receptors in living cells. Modified
      DNA aptamers that specifically recognize insulin receptors (IRs) with a high
      affinity were selected through the SELEX process. Using quantum dot-labeled
      aptamers, we successfully imaged and analyzed the diffusive motions of individual
      IRs in the plasma membranes of a variety of cell lines (HIR, HEK293, HepG2). We
      further explored the cholesterol-dependent movement of IRs to address whether
      cholesterol depletion interferes with IRs and found that cholesterol depletion of
      the plasma membrane by methyl-beta-cyclodextrin reduces the mobility of IRs. The
      aptamer-based single-molecule imaging of IRs will provide better understanding of
      insulin signal transduction through the dynamics study of IRs in the plasma
      membrane.

PMID- 24297060
TI  - Antibody-based magnetic nanoparticle immunoassay for quantification of
      Alzheimer's disease pathogenic factor.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that leads to a decline
      in cognitive and intellectual abilities and an irreversible mental deterioration.
      Based on multidisciplinary AD research, the most universally accepted hypotheses
      on AD pathogenesis are the intracerebral aggregate formation of beta-amyloid
      (Abeta) peptides. According to medical paradigmatic transition from medical
      treatment to early diagnostic prevention, scientists have considered
      physiological body fluid as a biomarker medium, in which the promising AD
      biomarkers could be verified. Recently, use of saliva has been considered as one
      of the diagnostic fluids over the past decade with meaningful diagnostic
      potential. We utilized saliva as a biomarker medium to correlate the salivary
      Abeta levels to AD pathological aspects, especially to the mild cognitive
      impairment group among AD patients, and to verify our detecting system to be
      sensitive enough for an early diagnostic tool. The identification of the salivary
      AD biomarkers using a facile microarraying method would motivate this study with
      the assistance of magnetically assembled antibody-conjugated nanoparticles and a
      photomultiplier tube as an optical detector. This simple magnetoimmunoassay
      system measures the photointensity generated by fluorescence, enables the
      quantification of the Abeta peptides from AD salivary samples, and consequently
      classifies the salivary Abeta levels into AD pathological aspects. This method
      demonstrates a facile approach enabling it to simply detect salivary Abeta
      peptides at a concentration as low as ~20  pg/ml. It is expected that our simple
      magnetoimmunoassay system may have a potential as a detector for low-level Abeta
      peptides with weak-fluorescence emission.

PMID- 24297061
TI  - In vivo imaging of human adipose-derived stem cells in Alzheimer's disease animal
      model.
AB  - Stem cell therapy is a promising tool for the treatment of diverse conditions,
      including neurodegenerative diseases such as Alzheimer's disease (AD). To
      understand transplanted stem cell biology, in vivo imaging is necessary.
      Nanomaterial has great potential for in vivo imaging and several noninvasive
      methods are used, such as magnetic resonance imaging, positron emission
      tomography, fluorescence imaging (FI) and near-infrared FI. However, each method
      has limitations for in vivo imaging. To overcome these limitations, multimodal
      nanoprobes have been developed. In the present study, we intravenously injected
      human adipose-derived stem cells (hASCs) that were labeled with a multimodal
      nanoparticle, LEO-LIVETM-Magnoxide 675 or 797 (BITERIALS, Seoul, Korea), into
      Tg2576 mice, an AD mouse model. After sequential in vivo tracking using Maestro
      Imaging System, we found fluorescence signals up to 10 days after injection. We
      also found strong signals in the brains extracted from hASC-transplanted Tg2576
      mice up to 12 days after injection. With these results, we suggest that in vivo
      imaging with this multimodal nanoparticle may provide a useful tool for stem cell
      tracking and understanding stem cell biology in other neurodegenerative diseases.

PMID- 24297062
TI  - Hyperspectral fluorescence imaging for cellular iron mapping in the in vitro
      model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss
      in the substantia nigra (SN) and elevated iron levels demonstrated by autopsy.
      Direct visualization of iron with live imaging techniques has not yet been
      successful. The aim of this study is to visualize and quantify the distribution
      of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1
      methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in
      SHSY5Y cells exposed to iron with ferric ammonium citrate (FAC, 100 MUM). The
      hyperspectral fluorescence signal of iron was examined using a high-resolution
      dark-field optical microscope system with signal absorption for the visible/near
      infrared spectral range. The 6-h group showed heavy cellular iron deposition
      compared with the 1-h group. The cellular iron was dispersed in a small
      particulate form, whereas the extracellular iron was aggregated. In addition,
      iron particles were found to be concentrated on the cell membrane/edge of
      shrunken cells. The iron accumulation readily occurred in MPP+-induced cells,
      which is consistent with previous studies demonstrating elevated iron levels in
      the SN. This direct iron imaging could be applied to analyze the physiological
      role of iron, and its application might be expanded to various neurological
      disorders involving metals, such as copper, manganese, or zinc.

PMID- 24297063
TI  - Cervical elongation following sacrospinous hysteropexy: a case series.
AB  - In recent years, pelvic floor surgeons have increasingly repaired pelvic organ
      prolapse around an intact uterus. Uterine conservation and hysteropexy have been
      driven by patient preference, less risk of mesh erosion, shorter operative time,
      and decreased blood loss and postoperative pain. We present a case series of
      patients with cervical elongation after vaginal sacrospinous hysteropexy using
      polypropylene mesh arms, a novel technique developed by the senior author. We
      defined cervical elongation as greater than or equal to a two-fold increase in
      cervical length compared with preoperative measurements. Of the 8 patients who
      underwent this procedure, 5 (62.5 %) had cervical elongation during the first
      year postoperatively. In the most severe case, the cervix extended to 4 cm beyond
      the hymenal ring. Most of the patients were mildly symptomatic and chose
      expectant management. The cases are reviewed in detail. A brief literature review
      on cervical elongation is presented.

PMID- 24297064
TI  - Evaluation of surgical instrument handling on polypropylene mesh using scanning
      electron microscopy.
AB  - INTRODUCTION AND HYPOTHESIS: To evaluate the effect of surgical instruments
      handling on polypropylene mesh using scanning electron microscopy (SEM). METHODS:
      We applied different surgical instruments, including a few robotic ones, to
      pieces of polypropylene mesh. SEM was used to evaluate the morphological changes
      with this intervention. RESULTS: Straight hemostat, laparoscopic atraumatic
      grasper, laparoscopic needle driver, and robotic instruments (Bipolar forceps,
      Cadiere forceps, PK dissecting forceps and SutureCut) were applied to the mesh.
      SEM images of tool-affected mesh regions in specimens handled by different
      instruments along with the images of intact mesh were obtained. Average mesh
      fiber diameters, as well as the average parameters characterizing instrument
      affected regions, were measured. There was substantial widening of the fibers in
      specimens handled by hemostat or a needle holder. An elliptical but much longer
      and narrower tool marking with more surface roughness was observed in mesh
      handled by a grasper. A ~25-MUm-wide and ~200-MUm-long strap was split on one
      side from the core of the fiber caused by Cadiere. CONCLUSIONS: There are
      morphological changes to polypropylene mesh caused by instrument handling. These
      changes are different depending on the instrument used. These alterations vary
      from changes in the surface creating roughness of the fiber, compression of the
      mesh with narrowing of the fiber in at least one direction or actual splitting or
      pitting of the fiber. Since there are no data regarding the effect of these
      morphological changes to the ultimate functioning of the mesh, surgeons should
      minimize mesh handling by instruments.

PMID- 24297066
TI  - Preface.

PMID- 24297065
TI  - Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade)
      and a phosphatidylinositol 3-kinase inhibitor (ZSTK474).
AB  - Proteasome inhibitors have been proven to be effective anticancer compounds in
      many tumor models, including glioblastoma multiforme (GBM). In this study, we
      found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell
      death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought
      to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of
      Velcade in anticancer therapy. Two GBM cell lines were used to detect the effects
      of Velcade and ZSTK474 alone or in combination in vitro. The combination of
      Velcade and ZSTK474 synergistically inhibited the proliferation of GBM cell
      lines. Cell apoptosis was increased when exposed to Velcade and ZSTK474 in
      combination as shown by Annexin V analysis. Treatment with both drugs led to
      downregulation of the p-Akt, p-4EBP1 and p-mTOR proteins as determined by western
      blot analysis. The anticancer ability of Velcade for glioblastoma multiforme was,
      therefore, enhanced by combination with the PI3K pathway inhibitor ZSTK474 in
      glioblastoma multiforme.

PMID- 24297067
TI  - Solidified self-nanoemulsifying formulation for oral delivery of combinatorial
      therapeutic regimen: part I. Formulation development, statistical optimization,
      and in vitro characterization.
AB  - PURPOSE: The present work reports rationalized development and characterization
      of solidified self-nanoemulsifying drug delivery system for oral delivery of
      combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable
      oil for the preparation of liquid SNEDDS was selected based on the maximum
      saturation solubility of both the drugs while surfactant and co-surfactant were
      selected based on their emulsification ability. Extreme vertices mixture design
      and 3(2) full factorial design were implemented for optimization of liquid SNEDDS
      and concentration of solid carrier in lyophilization mixture. Finally, extensive
      characterization of the developed formulation was performed and in vitro cellular
      uptake was evaluated in Caco-2 cell culture model. RESULTS: Extreme vertices
      mixture design indicated the desirability of 0.663, corresponded to 40:30:30 w/w
      as optimum ratio of oil (Capmul(r) MCM), surfactant (Cremophor RH 40) and co
      surfactant (Labrafil 1944CS) in liquid SNEDDS, which solubilized high amount of
      tamoxifen (10 mg/g) and quercetin (19.44 mg/g). A, 3(2) full factorial design
      revealed the optimum concentration of the selected solid carrier (Aerosil 200) of
      5.24% w/w and 1.61, when measured in terms of total solid content and liquid
      SNEDDS: Aerosil 200 ratio, respectively. The developed formulation revealed
      instantaneous emulsification (in < 2 min), while maintaning all the quality
      attributes even after storage at accelerated stability condition for 6 months.
      Finally, the developed formulation revealed 9.63-fold and 8.44-fold higher Caco-2
      uptake of tamoxifen and quercetin, respectively in comparison with free drug
      counterparts. CONCLUSIONS: The developed formulation strategy revealed a great
      potential for oral delivery of combination drugs having utmost clinical
      relevance.

PMID- 24297068
TI  - Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: in
      vivo and in vitro evaluation.
AB  - PURPOSE: To develop quercetin-loaded phospholipid vesicles, namely liposomes and
      PEVs (Penetration Enhancer-containing Vesicles), and to investigate their
      efficacy on TPA-induced skin inflammation. METHODS: Vesicles were made from a
      mixture of phospholipids, quercetin and polyethylene glycol 400 (PEG),
      specifically added to increase drug solubility and penetration through the skin.
      Vesicle morphology and self-assembly were probed by Cryo-Transmission Electron
      Microscopy and Small/Wide Angle X-ray Scattering, as well as the main physico
      chemical features by Light Scattering. The anti-inflammatory efficacy of
      quercetin nanovesicles was assessed in vivo on TPA-treated mice dorsal skin by
      the determination of two biomarkers: oedema formation and myeloperoxidase
      activity. The uptake of vesicles by 3T3 fibroblasts was also evaluated. RESULTS:
      Small spherical vesicles were produced. Their size and lamellarity was strongly
      influenced by the PEG content (0%, 5%, 10% v/v). The administration of vesicular
      quercetin on TPA-inflamed skin resulted in an amelioration of the tissue damage,
      with a noticeable attenuation of oedema and leukocyte infiltration, especially
      using 5% PEG-PEVs, as also confirmed by confocal microscopy. In vitro studies
      disclosed a massive uptake and diffusion of PEVs in dermal fibroblasts.
      CONCLUSIONS: The proposed approach based on quercetin vesicular formulations may
      be of value in the treatment of inflammatory skin disorders.

PMID- 24297069
TI  - Ocular delivery of pRNA nanoparticles: distribution and clearance after
      subconjunctival injection.
AB  - PURPOSE: RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA
      of bacteriophage phi29 DNA packaging motor were previously found to be
      thermodynamically stable. As the nanoparticles could have potential in ocular
      drug delivery, the objectives in the present study were to investigate the
      distribution of pRNA nanoparticles after subconjunctival injection and examine
      the feasibility to deliver the nanoparticles to the cells of cornea and retina.
      METHODS: Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double
      stranded RNA (dsRNA) were administered via subconjunctival injection in mice.
      Alexa647 dye was a control. Topical administration was performed for comparison.
      Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed
      using whole-body fluorescence imaging of the eyes. The numbers of cells in the
      ocular tissues with nanoparticle cell internalization were determined in
      fluorescence microscopy of dissected eye tissues. RESULTS: After subconjunctival
      injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes
      and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the
      cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of
      the retina. Topical administration was not effective in delivering the
      nanoparticles to the eye. CONCLUSIONS: The pRNA nanoparticles were delivered to
      the cells in the eye via subconjunctival injection, and cell internalization was
      achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X.
      Only the X-shape pRNA-X could enter the retina.

PMID- 24297070
TI  - Chitosan-based polyelectrolyte complexes as potential nanoparticulate carriers:
      physicochemical and biological characterization.
AB  - PURPOSE: To investigate the effect of polyelectrolytes on the formation and
      physicochemical properties of chitosan nanoparticles (CS-NPs) used for the
      delivery of an anticancer drug, doxorubicin (DOX). METHOD: Three DOX-loaded CS
      NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS
      DS/DOX NPs), and hyaluronic acid (CS-HA/DOX NPs) by using ionotropic gelation or
      complex coacervation. RESULTS: CS-TP/DOX NPs were the smallest, with an average
      size of ~100 nm and a narrow size distribution, while CS-DS/DOX and CS-HA/DOX NPs
      were ~200 nm in size. Transmission electron microscopy clearly showed a spherical
      shape for all the NPs. The strong binding affinity of DOX for the multiple
      sulfate groups in DS resulted in a sustained release profile from CS-DS/DOX NPs
      at pH 7.4, while CS-HA/DOX NPs exhibited faster DOX release. This trend was also
      present under acidic conditions, where release of DOX was significantly augmented
      because of polymer protonation. Compared to CS-TP/DOX or CS-DS/DOX NPs, CS-HA/DOX
      NPs showed superior cellular uptake and cytotoxicity in MCF-7 and A-549 cells,
      because of their ability to undergo CD44-mediated endocytosis. Pharmacokinetic
      studies clearly showed that all CS-NPs tested significantly improved DOX plasma
      circulation time and decreased its elimination rate constant. Consistent with the
      in vitro release data, CS-DS/DOX NPs exhibited a relatively better DOX plasma
      profile and enhanced blood circulation, compared to CS-HA/DOX or CS-TP/DOX NPs.
      Overall, these results demonstrated how NP design can influence their function.
      CONCLUSIONS: Taken together, CS-based polyelectrolyte complexes could provide a
      versatile delivery system with enormous potential in the pharmaceutical and
      biomedical sectors.

PMID- 24297071
TI  - CNS delivery and pharmacokinetic evaluations of DALDA analgesic peptide analog
      administered in Nano-sized oil-in-water emulsion formulation.
AB  - PURPOSE: Although neuro-active peptides are highly potent as central nervous
      system (CNS) therapeutics, their systemic delivery across the blood-brain barrier
      (BBB) is limited due to lack of permeability in the brain and rapid systemic
      metabolism. In this study, we aimed at enhancing the brain delivery and stability
      of chemically modified [D-Arg(2), Lys(4)]-dermorphin-(1-4)-amide)] (DALDA)
      peptide to achieve prolonged analgesic effects. METHODS: The C8-DALDA peptide
      analog was encapsulated in an oil-in-water nanoemulsion formulation made
      specifically with oils rich in omega-3 rich polyunsaturated fatty acid (PUFA) to
      enhance CNS availability. The nanoemulsion formulation was administered
      systemically in CD-1 mice and qualitative and quantitative biodistribution was
      evaluated. We have also examined the effect of curcumin, which is known to down
      regulate efflux transporters and inhibit systemic metabolism, on the
      pharmacokinetic properties of the peptide. RESULTS: Qualitative and quantitative
      biodistribution and pharmacokinetic studies in mice clearly demonstrated improved
      plasma and brain exposure of modified DALDA when administered in nanoemulsion,
      thereby providing an exciting opportunity towards improved efficacy and/or
      lowered dose of the peptide. The various dosing regimens tested for modified
      DALDA solution and curcumin nanoemulsion directed towards a novel combination
      strategy for improved systemic delivery of peptides across the BBB. CONCLUSIONS:
      Encapsulation of the drug in PUFA nanoemulsion is an effective strategy for
      delivery of peptides. This work provides a novel combination strategy for
      improved delivery of peptides to the brain.

PMID- 24297073
TI  - The success of PSN depends on dedicated volunteers.

PMID- 24297072
TI  - The influence of actuator materials and nozzle designs on electrostatic charge of
      pressurised metered dose inhaler (pMDI) formulations.
AB  - PURPOSE: To investigate the influence of different actuator materials and nozzle
      designs on the electrostatic charge properties of a series of solution metered
      dose inhaler (pMDI) aerosols. METHODS: Actuators were manufactured with flat and
      cone nozzle designs using five different materials from the triboelectric series
      (Nylon, Polyethylene terephthalate, Polyethylene-High density, Polypropylene
      copolymer and Polytetrafluoroethylene). The electrostatic charge profiles of pMDI
      containing beclomethasone dipropionate (BDP) as model drug in HFA-134a
      propellant, with different concentrations of ethanol were studied. Electrostatic
      measurements were taken using a modified electrical low-pressure impactor (ELPI)
      and the deposited drug mass assayed chemically using HPLC. RESULTS: The charge
      profiles of HFA 134a alone have shown strong electronegativity with all actuator
      materials and nozzle designs, at an average of -1531.34 pC +/- 377.34. The
      presence of co-solvent ethanol significantly reduced the negative charge
      magnitude. BDP reduced the suppressing effect of ethanol on the negative charging
      of the propellant. For all tested formulations, the flat nozzle design showed no
      significant differences in net charge between different actuator materials,
      whereas the charge profiles of cone designs followed the triboelectric series.
      CONCLUSION: The electrostatic charging profiles from a solution pMDI containing
      BDP and ethanol can be significantly influenced by the actuator material, nozzle
      design and formulation components. Ethanol concentration appears to have the most
      significant impact. Furthermore, BDP interactions with ethanol and HFA have an
      influence on the electrostatic charge of aerosols. By choosing different
      combinations of actuator materials and orifice design, the fine particle
      fractions of formulations can be altered.

PMID- 24297074
TI  - 40 years of ASPSN...celebrating you! 1974-2014.

PMID- 24297075
TI  - Letter from the president of PSNCB.

PMID- 24297076
TI  - Use of the dialectical behavior therapy skills and management of psychosocial
      stress with newly diagnosed breast cancer patients.
AB  - Stress-related health concerns have the potential to impact quality of life for
      patients with breast cancer. National cancer organizations such as the National
      Cancer Institute, the Institute of Medicine, and the National Comprehensive
      Cancer Network have acknowledged that all patients with cancer experience some
      level of distress during the course of illness and treatment. Literature on
      cancer suggests a range of expected distress from 20% to 50% among all patients
      diagnosed with cancer. Acknowledging and managing this distress with patients
      with cancer and providing them behavioral-based Interventions are important parts
      of cancer research. Dialectical Behavioral Therapy skill is are an empirically
      proven treatment modality across numerous patient populations. The main objective
      of this study was to evaluate the utilization and effectiveness of Dialectical
      Behavior Therapy skills modified for use with patients with breast cancer. 

PMID- 24297077
TI  - Anesthesia 101: everything you need to know.
AB  - Successful patient outcomes from an operative procedure require vigilance,
      diligence, and teamwork among the various providers involved with the surgical
      procedure. An understanding of the responsibilities and appreciation for the
      complexities of each healthcare provider's role in the operative process is
      essential to a harmonious relationship among the perioperative team to improve
      the working environment and provide safe patient care. The information provided
      in this article is based on commonly observed practices in the anesthesia
      community with the caveat that the choices can vary considerably and are
      influenced by patient presentation and surgical requirements. 

PMID- 24297078
TI  - Daily care for acne, hyperpigmentation, aging, and sensitive skin.
AB  - Choosing the correct daily care regimen for your patients' specific skin
      condition does not have to become an overwhelming task. Determining which
      ingredients to include can form the foundation for the successful treatment of
      each of the most common skin conditions. In turn, you and your patients will
      achieve quick and long-term success. Although each patient's skin is a unique
      combination of their environment, lifestyle choices, hereditary background, and
      current product usage, there are specific ingredients that will help minimize the
      appearance of the more commonly treated skin conditions: acne, hyperpigmentation,
      aging, and sensitive skin. 

PMID- 24297080
TI  - The "nuts & bolts" of becoming an aesthetic provider: part 1-how do I get
      started?

PMID- 24297081
TI  - Assessment of health status of adolescent burn victims undergoing rehabilitation:
      a cross-sectional field study.
AB  - Teenagers may experience physiological and psychological changes when they suffer
      from a severe burn. The aim of this study was to assess the state of health of
      teenagers who were undergoing a rehabilitation process following a severe burn. A
      cross-sectional field study was carried out with 63 teenagers and young adults
      who had suffered burns. The tests applied were social, demographic, and clinical
      instruments. The specific tests included the Burn Specific Health Scale-Revised,
      Beck Depression Inventory, Rosenberg's Self-Esteem Scale, and Functional
      Independence Measurement. The results were analyzed by using descriptive
      statistics, multivariate analysis of variance, variance analysis, and Cronbach's
      reliability analysis. The social and demographic analysis of the population has
      shown a prevalence of female (60.3%), single subjects (93.7%), and ages between
      12 and 20 years (mean age of 15.95 years). The mean total body surface area burn
      was 23.84%, with accidents as the main causative factor (92.10%). More than half
      (52.4%) reported functional and aesthetic effects after the burn, with 81%
      concerned about the visible scar. Cronbach's reliability analysis has shown
      statistically confident results for all the instruments as applied. The
      multivariate analysis showed a correlation between the work domain and marital
      status, whereas there was no evidence to show a correlation between sex, age,
      physical or aesthetic sequelae or visibility of burns, and depression, self
      esteem, functional independence, or current state of health. The results obtained
      prove the reliability of the instruments applied, making it possible to assess
      the state of teenagers and young adults health during the rehabilitation process.

PMID- 24297082
TI  - Pressure ulcer staging-revisited.

PMID- 24297083
TI  - Vocal caricatures reveal signatures of speaker identity.
AB  - What are the features that impersonators select to elicit a speaker's identity?
      We built a voice database of public figures (targets) and imitations produced by
      professional impersonators. They produced one imitation based on their memory of
      the target (caricature) and another one after listening to the target audio
      (replica). A set of naive participants then judged identity and similarity of
      pairs of voices. Identity was better evoked by the caricatures and replicas were
      perceived to be closer to the targets in terms of voice similarity. We used this
      data to map relevant acoustic dimensions for each task. Our results indicate that
      speaker identity is mainly associated with vocal tract features, while perception
      of voice similarity is related to vocal folds parameters. We therefore show the
      way in which acoustic caricatures emphasize identity features at the cost of
      loosing similarity, which allows drawing an analogy with caricatures in the
      visual space. 

PMID- 24297084
TI  - A systematic review of the characteristics associated with recall rates,
      detection rates and positive predictive values of computed tomography screening
      for lung cancer.
AB  - BACKGROUND: Low-dose computed tomography (LDCT) screening has been shown to
      reduce mortality from lung cancer but at a substantial cost in diagnostic
      activity. The objective of this study was to investigate the characteristics of
      screening programmes associated with recall rates, detection rates and positive
      predictive values (PPVs). DESIGN: We conducted a systematic review of randomised
      trials and observational studies on LDCT screening for lung cancer. A meta
      regression using random-effect logistic regressions was carried out to assess
      factors influencing recall rates for further investigation, cancer detection
      rates and PPVs of recall. RESULTS: We used data from 63 372 prevalent screens
      from 16 studies of LDCT screening for lung cancer and 79 302 incident screens
      from nine studies. In univariable analysis, the use of a cut-off size to define
      nodules warranting further investigation at prevalent screens reduced recall
      rates [odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.24-0.82 and OR =
      0.42, 95% CI 0.21-0.84 for cut-off sizes of 3-4 and 5-8 mm, respectively],
      without significant changes in detection rates and PPVs. The number of readers (1
      or >=2) was not associated with changes in recall rates, detection rates and PPVs
      at prevalent and incident screens. Using the volumetry software at incident
      screens significantly increased the PPV (OR = 5.02, 95% CI 1.65-15.28) as a
      result of a decrease in recall rates (OR = 0.25, 95% CI 0.12-0.51), without
      significant changes in detection rates. CONCLUSION: These results highlight the
      value of using a cut-off size for nodules warranting further investigation with
      lower recall rates at prevalent screens, whereas the volumetric assessment
      software at incident screens results in lower recall rates and higher PPVs. The
      presence of positron emission tomography in the work-up protocol might be
      associated with lower rates of surgical procedures for benign findings, although
      this hypothesis deserves further investigation.

PMID- 24297086
TI  - Interface properties of CVD grown graphene transferred onto MoS2(0001).
AB  - Heterostructures of dissimilar 2D materials are potential building blocks for
      novel materials and may enable the formation of new (photo)electronic device
      architectures. Previous work mainly focused on supporting graphene on insulating
      wide-band gap materials, such as hex-BN and mica. Here we investigate the
      interface between zero-band gap semiconductor graphene and band-gap semiconductor
      MoS2 as a potential building block for entirely 2D-material based semiconducting
      devices. We show that solution transfer results in water trapping at the
      interface which may be removed by annealing to ~300  degrees C in a vacuum. After
      removal of the water, by high temperature annealing, ultraflat graphene is
      obtained on MoS2 with only a very weak moire pattern observable in scanning
      tunneling microscopy images due to lattice mismatch and random alignment of
      graphene with respect to the MoS2 substrate. Photoemission spectroscopy indicates
      interface dipole formation, p-type doping of graphene by ~0.09 eV downward shift
      of the Fermi-level below the Dirac point, and a negative space charge region in
      bulk MoS2. Interestingly, valence band spectra of the graphene covered MoS2
      surface indicate a band gap narrowing of the MoS2 surface by ~0.1 eV. This band
      gap reduction at the surface is further evidence that interlayer van der Waals
      interactions critically influence the band structure of 2D-layered
      dichalcogenides and suggest that interfacing with dissimilar van der Waals
      materials allows tuning of their electronic properties.

PMID- 24297085
TI  - Clinicopathological features of nonsmall cell lung carcinomas with BRAF
      mutations.
AB  - BACKGROUND: Recently, driver tyrosine kinase gene mutations have been detected in
      malignant tumors, including lung tumors. Notwithstanding their attractiveness as
      targets for molecular therapy, limited information is available regarding BRAF
      mutated lung carcinomas. MATERIALS AND METHODS: BRAF mutation status was
      determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases
      using high-resolution melting analysis (HRMA) followed by Sanger sequencing
      and/or deep sequencing using next generation sequencer. RESULTS: BRAF mutations
      were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous
      cell carcinoma). In the 26 cases, 13 mutation genotypes were identified,
      including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%),
      and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes
      (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer.
      The overall survival rate was not significantly different between patients with
      wild-type BRAF and those with V600E or non-V600E BRAF mutations (P = 0.49 and P =
      0.15, respectively). Histomorphological analysis revealed that focal clear cell
      changes were present in 75% of V600E-mutated tumors. All V600E BRAF-mutated
      tumors were negative for other driver gene alterations including epidermal growth
      factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene
      translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and
      one G464E/G466R) showed concomitant EGFR mutations. CONCLUSION: The frequency of
      BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF
      mutation status lacked prognostic significance in this patient population.

PMID- 24297088
TI  - Time to quit that marathon running? Not quite yet!

PMID- 24297087
TI  - Exogenous bFGF or TGFbeta1 accelerates healing of reconstructed dura by CO2 laser
      soldering in minipigs.
AB  - This study aims to explore the probable mechanism of better result of dural
      reconstruction by CO2 laser soldering and the effect of exogenous basic
      fibroblast growth factor (bFGF) or transforming growth factor-beta1(TGFbeta1) on
      wound healing. In part I of the study, ten minipigs were randomized into two
      equal groups, and the dural defects were reconstructed by conventional fibrin
      glue (FG) bonding (group I a) or by CO2 laser soldering (group Ib). In part II,
      36 minipigs were randomized into three equal groups, and the dural defect was
      reconstructed by CO2 laser soldering; then exogenous bFGF or TGFbeta1 was
      administered in group IIb and group IIc, respectively, while group IIa served as
      control group. The dural specimens were harvested at 1st week postoperatively in
      part I; and at 1st, 2nd, 3rd, and 4th week postoperatively in part II, they were
      examined for healing condition and subjected to hematoxylin-eosin (HE) staining
      and immunohistochemical (IHC) staining with antibodies against bFGF and TGFbeta1.
      In part I, group Ib showed higher fibroblast cell density than group Ia (P <
      0.05). The optical density (OD) for IHC staining with antibodies against bFGF of
      group Ib was significantly higher than that of group Ia (P < 0.05), and for IHC
      staining with antibodies against TGFbeta1, group Ib showed positive staining
      while group Ia was negative. In part II, administering exogenous bFGF or TGFbeta1
      made a left shift of fibroblast cell number-time curve compared with control
      group. For specimens' IHC staining with antibodies against bFGF, the OD of group
      IIb was higher than that of group IIa in the corresponding time. For specimens'
      IHC staining with antibodies against TGFbeta1, the OD of groups IIb and IIc was
      both higher than that of group IIa (P < 0.05 and P < 0.01, respectively). In
      conclusion, CO2 laser may trigger fibroblast proliferation through stimulating
      the secretion of bFGF and TGFbeta1. Topically administering exogenous bFGF or
      TGFbeta1 could accelerate the healing of the reconstructed dura by enhancing
      secretion of bFGF and/or TGFbeta1 and promoting the process of fibroblast
      gathering-degrading.

PMID- 24297089
TI  - Electrophilic ipso-iodocyclization of N-benzyl-N-(1-naphthyl)propiolamides:
      synthesis of complex polycyclic lactams.
AB  - An intramolecular electrophilic ipso-iodocyclization of N-benzyl-N-(1
      naphthyl)propiolamides combined with the Friedel-Crafts-type reaction for the
      synthesis of complex polycyclic lactams is reported. The resulting iodinated
      cyclization product can provide a very useful handle for further structural
      manipulation. 

PMID- 24297090
TI  - Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of
      glucocorticoids in men with the metabolic syndrome? A randomized controlled
      trial.
AB  - OBJECTIVE: Anti-inflammatory glucocorticoid (GC) therapy often induces
      hyperglycemia due to insulin resistance and islet-cell dysfunction. Incretin
      based therapies may preserve glucose tolerance and pancreatic islet-cell
      function. In this study, we hypothesized that concomitant administration of the
      dipeptidyl peptidase-4 inhibitor sitagliptin and prednisolone in men at high risk
      to develop type 2 diabetes could protect against the GC-induced diabetogenic
      effects. DESIGN AND METHODS: Men with the metabolic syndrome but without diabetes
      received prednisolone 30  mg once daily plus sitagliptin 100  mg once daily
      (n=14), prednisolone (n=12) or sitagliptin alone (n=14) or placebo (n=12) for 14
      days in a double-blind 2 * 2 randomized-controlled study. Glucose, insulin, C
      peptide, and glucagon were measured in the fasted state and following a
      standardized mixed-meal test. beta-cell function parameters were assessed both
      from a hyperglycemic-arginine clamp procedure and from the meal test. Insulin
      sensitivity (M-value) was measured by euglycemic clamp. RESULTS: Prednisolone
      increased postprandial area under the curve (AUC)-glucose by 17% (P<0.001 vs
      placebo) and postprandial AUC-glucagon by 50% (P<0.001). Prednisolone reduced 1st
      and 2nd phase glucose-stimulated- and combined hyperglycemia-arginine-stimulated
      C-peptide secretion (all P <= 0.001). When sitagliptin was added, both clamp
      measured beta-cell function (P=NS for 1st and 2nd phase vs placebo) and
      postprandial hyperglucagonemia (P=NS vs placebo) remained unaffected. However,
      administration of sitagliptin could not prevent prednisolone-induced increment in
      postprandial glucose concentrations (P<0.001 vs placebo). M-value was not altered
      by any treatment. CONCLUSION: Fourteen-day treatment with high-dose prednisolone
      impaired postprandial glucose metabolism in subjects with the metabolic syndrome.
      Concomitant treatment with sitagliptin improved various aspects of pancreatic
      islet-cell function, but did not prevent deterioration of glucose tolerance by GC
      treatment.

PMID- 24297091
TI  - Antiviral Potential of Selected Starter Cultures, Bacteriocins and D,L-Lactic
      Acid.
AB  - The antiviral potential of selected bacteria species [lactic acid bacteria (LAB)
      and micrococcaceae] was examined. By this, the effect of their cell-free
      supernatants as well as of certain species-related metabolites (sakacin A, nisin,
      and lactic acid) was investigated on different viruses after exposure at 24 
      degrees C for 3 days. Viruses were incubated with supernatants and metabolites in
      a dilution ratio of 1:10. Data for antiviral effects towards murine norovirus S99
      (MNV), influenza A virus A/WSN/33 (H1N1), Newcastle disease virus Montana (NDV)
      and feline herpesvirus KS 285 (FHV) were generated in vitro simulating pH and
      temperature conditions according to raw sausage fermentations. Investigations
      showed no antiviral effect of sakacin A and nisin on MNV, H1N1, FHV and NDV.
      Furthermore, the antiviral potential of D,L-lactic acid was determined for MNV
      and H1N1. At raw sausage-related pH values (5.0-6.2) it could be shown that the
      virus titre for MNV and H1N1 was reduced by a maximum of 3.25 log and 2.5 log
      units, respectively. In addition, 29 culture supernatants of different bacteria
      species, mainly LAB and staphylococci, were tested for their antiviral activity
      against MNV. Only the cell-free supernatant of a Lb. curvatus strain showed a
      higher virus titre reduction of MNV by 1.25 log units compared to the control.
      Further studies on the characterisation of this cell-free supernatant were
      carried out, however, the antiviral substance could not be identified so far. 

PMID- 24297092
TI  - Why should nanoscience students be taught to be ethically competent?
AB  - During the education of scientists at the university level the students become
      more and more specialized. The specialization of the students is a consequence of
      the scientific research becoming specialized as well. In the interdisciplinary
      field of nanoscience the importance of specialization is also emphasized
      throughout the education. Being an interdisciplinary field of study the
      specialization in this area is not focused on scientific disciplines, but on the
      different branches of the research. Historically ethics has not been a priority
      in science education, however, in recent years the importance of such teachings
      has been highly recognize especially in medicine, biotechnology and engineering.
      The rapid development, the many new and unknown areas and the highly specialized
      focus of nanotechnology suggest the importance of having ethically competent
      researchers. In this article the importance of ethical competence in nanoscience
      research is argued for by an example of a dilemma that could occur in a research
      project. The dilemma is analyzed using two different ethical views, generating
      two different choices for action. It is seen that the dilemma can have more than
      one solution and that ethical competence can help in justifying the choice of
      solution in a specific situation. Furthermore it is suggested that a way to reach
      this competence is through education in ethics incorporated into the nanoscience
      education curriculum. 

PMID- 24297093
TI  - Outcome of 23-gauge pars plana vitrectomy for pediatric vitreoretinal conditions.
AB  - PURPOSE: To evaluate the feasibility and short-term outcome of 23-gauge
      vitrectomy in children for various vitreoretinal conditions. METHODS: A
      retrospective chart review was conducted of consecutive children younger than 14
      years who underwent 23-gauge transconjunctival sutureless vitrectomy for various
      vitreoretinal conditions from January 2008 to December 2011 at a tertiary care
      center. RESULTS: Thirty-seven eyes of 31 children were included. There were 20
      boys and 11 girls, aged between 1.25 months and 14 years (median: 10 years, mean:
      7.23 years). The surgical indications were subluxated crystalline lens,
      retinopathy of prematurity stage 4, post-traumatic cataract with ruptured
      capsule, vitreous hemorrhage, dislocated crystalline lens, endophthalmitis,
      retinal detachment with vitreous hemorrhage, dislocated intraocular lens,
      epiretinal membrane, and increased intraocular pressure after intravitreal
      steroid implantation. Postoperative complications included loose blood, retinal
      detachment, early postoperative hypotony, and preretinal bleeding. CONCLUSIONS:
      The 23-gauge transconjunctival sutureless vitrectomy approach in children appears
      safe and effective.

PMID- 24297094
TI  - Elevated risk of clinical fractures and associated risk factors in patients with
      systemic lupus erythematosus versus matched controls: a population-based study in
      the United Kingdom.
AB  - The incidence of clinical fractures and the associated factors were assessed in
      patients with systemic lupus erythematosus (SLE) versus matched controls. We
      found an increased fracture risk in SLE patients compared to controls.
      Glucocorticoid use, longer disease duration, neuropsychiatric disease
      complications and previous osteoporotic fractures were identified as associated
      factors. INTRODUCTION: The aims of this study were to estimate the risk of
      clinical fractures in patients with SLE versus matched controls and to evaluate
      the risk factors associated with clinical fractures in SLE. METHODS: This is a
      population-based cohort study using the Clinical Practice Research Datalink (from
      1987-2012). Each SLE patient (n = 4,343) was matched with up to six controls (n =
      21,780) by age and sex. Clinical fracture type was stratified according to the
      WHO definitions into osteoporotic and non-osteoporotic fracture. Cox proportional
      hazards calculated relative rates (RR) of clinical fracture and time interaction
      terms to evaluate the timing patterns of fracture. Clinical fracture rates in SLE
      patients, stratified by age, gender, type of fracture, disease duration and
      therapy variables, were compared with those rates in controls. RESULTS: Follow-up
      durations were 6.4 years in SLE patients and 6.6 years in controls. SLE patients
      had a 1.2-fold increased clinical fracture risk compared to controls (adjusted RR
      = 1.22, 95% CI = 1.05-1.42), and the risk further increased with a longer disease
      duration. Glucocorticoid (GC) use in the previous 6 months raised the risk of
      clinical fracture (adjusted RR = 1.27, 95% CI = 1.02-1.58). Cerebrovascular
      events, seizures and previous osteoporotic fractures were identified as
      predictors of clinical fractures. CONCLUSIONS: We found an increased risk of
      clinical fracture in SLE patients compared to controls. GC use in the previous 6
      months and longer disease duration are associated with the increased fracture
      risk in SLE. Patients with neuropsychiatric organ damage or previous osteoporotic
      fractures are also at increased risk of the occurrence of clinical fractures.

PMID- 24297095
TI  - Aseptic necrosis at multiple localisations in a lupus patient with lymphoma.
AB  - Avascular or aseptic necrosis is a well-defined entity leading to the degradation
      of cellular elements of the bone. The pathogenesis of osteonecrosis (ON) is still
      unknown. There are two main types of ON: traumatic or non-traumatic. Several
      clinical entities could associate with ON, systemic diseases, environmental
      factors, pregnancy, systemic autoimmune or rheumatic diseases, thrombophilia,
      corticosteroid therapy, cytotoxic dugs, infections, metabolic and hematologic
      diseases, etc. Corticosteroids (CS) are still the most frequently used
      therapeutic options in the early phase and during flares of these diseases.
      Inflammatory cytokines and antibodies have been described to participate in the
      pathogenesis of ON. The infiltrative disorders of the bone marrow could also
      contribute to the development of ON. Hereby, we describe a female patient with
      NHL followed by SLE in whom ON has developed at least in two localisations. Lupus
      flare, long-term CS therapy, lymphoma relapse or the presence of antiphospholipid
      antibodies were excluded. Although the bi-localised ON could be contributed to
      immunologic factors or trauma, the exact aetiology in this case could not be
      elucidated. 

PMID- 24297096
TI  - Melatonin protects MG63 osteoblast-like cells from hydrogen peroxide-induced
      cytotoxicity by maintaining mitochondrial function.
AB  - Osteoporosis is a bone disease that has been connected with reactive oxygen
      species (ROS)-induced cytotoxicity. Mitochondrial dysfunction may be involved in
      the mechanism underlying ROS-induced cytotoxicity. It has been demonstrated that
      melatonin may exert cytoprotective effects by improving mitochondrial energetics
      and functions in several models of oxidative damage. In the present study, the
      MG63 osteoblast-like cell line was exposed to different concentrations of
      hydrogen peroxide (H2O2; 0, 100, 200, 400 or 800 uM) for 8 h, and 200 or 400 uM
      H2O2 for various periods of time (0.5, 4, 8 or 12 h). Results showed that H2O2
      significantly reduced cell viability, increased the release of lactate
      dehydrogenase, increased the levels of ROS and malondialdehyde, reduced the
      concentration of adenosine-5'-triphosphate, disrupted the mitochondrial membrane
      potential (DeltaPsim) and decreased the mitochondrial DNA copy number in MG63
      cells. However, pretreatment with melatonin effectively decreased all of these
      H2O2-induced changes in cytotoxicity and mitochondrial dysfunction in MG63 cells.
      The protective effects of melatonin may be attributed to its ability to maintain
      mitochondrial function in H2O2-treated cells. This study suggests that melatonin
      is a potential pharmacological agent for preventing ROS-induced bone loss in
      diseases such as osteoporosis.

PMID- 24297097
TI  - Chromatic visual evoked potentials in paediatric population.
AB  - BACKGROUND: The purpose of this study was to investigate chromatic visual evoked
      potential (cVEP) response characteristics during the first year of life and to
      collect as large database of healthy baby responses as possible. This study also
      complements our previous studies on cVEP in schoolchildren and preschool
      children. METHODS: Forty-four healthy babies aged 3-12 months were binocularly
      tested. cVEP were recorded to isoluminant red-green (R-G) and blue-yellow (B-Y)
      stimuli. The stimulus represented a circle composed of horizontal sinusoidal
      gratings with 90 % chromatic contrast and spatial frequency of 2 cycles/deg. Two
      stimulus sizes (7 degrees  and 21 degrees ) and onset-offset mode of stimulation
      (On-300 ms, Off-700 ms) were used. cVEP were recorded from Oz (mid-occipital)
      position with the reference at Fz. Waveform characteristics and its changes
      throughout the first year of life were studied. RESULTS: Chromatic visual evoked
      potential responses were reliably recorded in all but two youngest babies.
      Characteristic cVEP response consisted of negative-positive-negative complex,
      positive (P) wave being far more prominent than both negative waves (N1 and N2).
      cVEP response to larger stimulus size (21 degrees ) showed shorter latency and
      higher amplitude to both (R-G) and (B-Y) stimuli compared to smaller stimulus
      size (7 degrees ). The same was true when comparing R-G versus B-Y stimulus: R-G
      responses showed higher amplitude and shorter latency than B-Y response, for both
      stimulus sizes. P wave latency shortened with increasing age throughout the first
      year of life, both for R-G (R (2) = 0.59) and B-Y (R (2) = 0.41) 21 degrees 
      stimulation. P wave amplitude did not show significant changes throughout the
      first year of life. CONCLUSIONS: Chromatic visual evoked potential can be
      reliably recorded after the age of 3 months and show significant maturational
      changes throughout the first year of life.

PMID- 24297098
TI  - Recombinant antibody mediated delivery of organelle-specific DNA pH sensors along
      endocytic pathways.
AB  - DNA has been used to build nanomachines with potential in cellulo and in vivo
      applications. However their different in cellulo applications are limited by the
      lack of generalizable strategies to deliver them to precise intracellular
      locations. Here we describe a new molecular design of DNA pH sensors with
      response times that are nearly 20 fold faster. Further, by changing the sequence
      of the pH sensitive domain of the DNA sensor, we have been able to tune their pH
      sensitive regimes and create a family of DNA sensors spanning ranges from pH 4 to
      7.6. To enable a generalizable targeting methodology, this new sensor design also
      incorporates a 'handle' domain. We have identified, using a phage display screen,
      a set of three recombinant antibodies (scFv) that bind sequence specifically to
      the handle domain. Sequence analysis of these antibodies revealed several
      conserved residues that mediate specific interactions with the cognate DNA
      duplex. We also found that all three scFvs clustered into different branches
      indicating that their specificity arises from mutations in key residues. When one
      of these scFvs is fused to a membrane protein (furin) that traffics via the cell
      surface, the scFv-furin chimera binds the 'handle' and ferries a family of DNA pH
      sensors along the furin endocytic pathway. Post endocytosis, all DNA nanodevices
      retain their functionality in cellulo and provide spatiotemporal pH maps of
      retrogradely trafficking furin inside living cells. This new molecular technology
      of DNA-scFv-protein chimeras can be used to site-specifically complex DNA
      nanostructures for bioanalytical applications. 

PMID- 24297099
TI  - Natal dispersal based on past and present environmental phenology in the pied
      flycatcher (Ficedula hypoleuca).
AB  - Natal dispersal allows individuals to reach suitable breeding sites. The effect
      of present plant phenology as a cue for dispersal into areas with favourable
      stages of development has been well established across avian and mammalian taxa.
      However, the effect of past experience is less understood. We studied the effect
      of past and present phenology of the environment on the direction and distance of
      natal dispersal in a passerine bird, the pied flycatcher (Ficedula hypoleuca). We
      monitored spring settlement of local recruits in six nest box plots along a 10-km
      stretch of a south-north gradient of plant and caterpillar food development. We
      found that males used both past experience of caterpillar phenology from early
      life and actual plant phenology during the recruitment season as independent cues
      for breeding settlement. Males that had experienced a mismatch with the
      caterpillar food peak as a nestling, and/or those that arrived late in the spring
      in the recruitment year, moved north of their natal site, whereas males that had
      experienced a better match with the caterpillars as a nestling, and/or those that
      migrated earlier in the spring, settled at a similar site or more to the south.
      In females, no such effects were found, suggesting that the usage of phenological
      cues is sex specific. In summary, tracking environmental phenology by natal
      dispersal may represent an effective mechanism for settling in new favourable
      areas, and may thus potentially cause rapid change of a species' geographical
      breeding range in response to climate change. 

PMID- 24297100
TI  - Resolving the forbidden band of SF6.
AB  - Sulfur hexafluoride is an important molecule for modeling thermophysical and
      polarizability properties. It is also a potent greenhouse gas of anthropogenic
      origin, whose concentration in the atmosphere, although very low is increasing
      rapidly; its global warming power is mostly conferred by its strong infrared
      absorption in the nu3 S-F stretching region near 948 cm(-1). This heavy species,
      however, features many hot bands at room temperature (at which only 31% of the
      molecules lie in the ground vibrational state), especially those originating from
      the lowest, v6 = 1 vibrational state. Unfortunately, the nu6 band itself (near
      347 cm(-1)), in the first approximation, is both infrared- and Raman-inactive,
      and no reliable spectroscopic information could be obtained up to now and this
      has precluded a correct modeling of the hot bands. It has been suggested
      theoretically and experimentally that this band might be slightly activated
      through Coriolis interaction with infrared-active fundamentals and appears in
      high pressure measurements as a very faint, unresolved band. Using a new
      cryogenic multipass cell with 93 m optical path length and regulated at 163 +/- 2
      K temperature, coupled to synchrotron radiation and a high resolution
      interferometer, the spectrum of the nu6 far-infrared region has been recorded.
      Low temperature was used to avoid the presence of hot bands. We are thus able to
      confirm that the small feature in this region, previously viewed at low
      resolution, is indeed nu6. The fully resolved spectrum has been analyzed, thanks
      to the XTDS software package. The band appears to be activated by faint Coriolis
      interactions with the strong nu3 and nu4 fundamental bands, resulting in the
      appearance of a small first-order dipole moment term, inducing unusual selection
      rules. The band center (nu6 = 347.736707(35) cm(-1)) and rovibrational parameters
      are now accurately determined for the v6 = 1 level. The nu6 perturbation-induced
      dipole moment is estimated to be 33 +/- 3 MUD and the nu6 integrated intensity to
      be 0.0035 km mol(-1). 

PMID- 24297101
TI  - Magnetic composite BiOCl-SrFe12O19: a novel p-n type heterojunction with enhanced
      photocatalytic activity.
AB  - The magnetic composite BiOCl-SrFe12O19, a novel p-n type heterojunction was
      synthesized by hydrolysis with a medium temperature sintering method. The
      microstructure and magnetic properties of the prepared material were
      characterized by FTIR, XRD, SEM, TEM, HRTEM, SAED, and VSM. The results showed
      the [001] facet of BiOCl with high photocatalytic activity was exposed in the
      BiOCl-SrFe12O19. The heterostructured BiOCl-SrFe12O19 had better magnetic
      properties, contributing to its reuse and improvement in photocatalysis.
      Moreover, the composite was blessed with excellent photocatalytic activity and
      stability. In the BiOCl-SrFe12O19 system, SrFe12O19 not only inhibited the growth
      of BiOCl along the [001] direction to enhance the exposure of the [001] wafer,
      but also acted as a sensitizer absorbing light irradiation. The magnetic field
      generated from SrFe12O19 made BiOCl, under light irradiation, produce more photo
      induced electrons and holes and simultaneously hampered their recombination. For
      the first time we propose the possible mechanism of how to enhance photocatalytic
      activity by a magnetic field effect originating from the magnetic photocatalyst
      itself. 

PMID- 24297102
TI  - A comparison of SF-36 summary measures of physical and mental health for women
      across the life course.
AB  - BACKGROUND: Physical and mental component summary scores (PCS and MCS,
      respectively) are often used to summarise SF-36 quality of life subscales. This
      paper investigates PCS and MCS across the life course and compares the
      trajectories obtained from two different methods of calculation. METHODS: The
      Australian Longitudinal Study on Women's Health is a population-based study with
      three cohorts of women and SF-36 surveys taken at multiple time points. Scoring
      coefficients for each component score were determined using factor analysis with
      uncorrelated (orthogonal) and correlated (oblique) rotation at the baseline
      survey, which were then used to compute correlated and uncorrelated PCS and MCS
      scores at each survey (scaled to have mean of 50 and standard deviation of 10 at
      baseline). RESULTS: For both methods, PCS declined progressively across the
      lifespan, while MCS rose in young and mid-age women to a peak and subsequently
      declined in later life. Differences were apparent between correlated and
      uncorrelated scores, most notably for MCS in the older cohort, where correlated
      MCS reached 54.6 but still less than uncorrelated MCS, with a random effects
      model indicating 1.63 (95% confidence intervals 1.58-1.67) units difference; it
      then declined to a score of 51.2 by the last survey and the difference widened to
      3.44 (3.38-3.50) units compared with the uncorrelated MCS. CONCLUSIONS: PCS and
      MCS have distinct trajectories through life, with differences in results from
      correlated and uncorrelated component summary scores. The divergence is most
      notable with MCS, especially for older women, suggesting that correlated MCS and
      PCS should be used when examining change in health over time in this age group.

PMID- 24297103
TI  - Evidence needs to be translated, whether or not it is complete.

PMID- 24297104
TI  - Asymmetric synthesis of drug-like spiro[chroman-3,3'-indolin]-2'-ones through
      aminal-catalysis.
AB  - Asymmetric synthesis of drug-like functionalized spiro[chroman-3,3'-indolin]-2'
      ones 5 containing three contiguous stereocenters with high diastereo- and
      enantioselectivities was achieved using the reflexive-Michael (r-M) reaction of
      unmodified hydroxyenals 1 with various (E)-3-alkylideneindolin-2-ones 2 in the
      presence of (R)-DPPOTMS/AcOH (R)-3/4b as a catalyst at room temperature. Chiral
      spiro[chroman-3,3'-indolin]-2'-ones 5 were transformed into the functionalized
      spiranes 7, 9, and 10 in good yields with high selectivity through Wittig, TCRA,
      acetal protection and reduction reactions, respectively. Supporting evidence for
      the reaction pathway through the formation of the important catalytic species of
      "aminals" was observed through NMR and ESI-HRMS analysis of an ongoing reaction
      between 1 and (R)-3 in CDCl3 and also shown by the structural requirement in
      hydroxyenals 1 to generate the "aminals" with (R)-3 through controlled
      experiments.

PMID- 24297105
TI  - Orthopaedic surgery education in India.

PMID- 24297106
TI  - Developing a pathway for high-value, patient-centered total joint arthroplasty.
AB  - BACKGROUND: Total joint arthroplasty (TJA) is one of the most widely performed
      elective procedures; however, there are wide variations in cost and quality among
      facilities where the procedure is performed. QUESTIONS/PURPOSES: The purposes of
      this study were to (1) develop a generalizable clinical care pathway for primary
      TJA using inputs from clinical, academic, and patient stakeholders; and (2)
      identify system- and patient-level processes to provide safe, effective,
      efficient, and patient-centered care for patients undergoing TJA. METHODS: We
      used a combination of quantitative and qualitative methods to design a care
      pathway that spans 14 months beginning with the presurgical office visit and
      concluding 12 months after discharge. We derived care suggestions from interviews
      with 16 hospitals selected based on readmission rates, cost, and quality (n = 10)
      and author opinion (n = 6). A 32-member multistakeholder panel refined the
      pathway during a 1-day workshop. Participants were selected based on leadership
      in orthopaedic (n = 4) and anesthesia (n = 1) specialty societies; involvement in
      organizations specializing in safety and high reliability care (n = 3), lean
      production/consumption of care (n = 3), and patient experience of care (n = 3);
      membership in an interdisciplinary care team of a hospital selected for
      interviewing (n = 8); recent receipt of a TJA (n = 1); and participation in the
      pathway development team (n = 9). RESULTS: The care pathway includes 40 suggested
      processes to improve care, 37 techniques to reduce waste, and 55 techniques to
      improve communication. Central themes include standardization and process
      improvement, interdisciplinary communication and collaboration, and
      patient/family engagement and education. Selected recommendations include
      standardizing care protocols and staff roles; aligning information flow with
      patient and process flow; identifying a role accountable for care delivery and
      communication; managing patient expectations; and stratifying patients into the
      most appropriate care level. CONCLUSIONS: We developed a multidisciplinary
      clinical care pathway for patients undergoing TJA based on principles of high
      value care. The pathway is ready for clinical testing and context-specific
      adaptation. LEVEL OF EVIDENCE: Level V, therapeutic study. See the Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24297108
TI  - CORR Insights(r): Are race and sex assessment associated with the occurrence of
      atypical femoral fractures?

PMID- 24297107
TI  - Risk of impingement and third-body abrasion with 28-mm metal-on-metal bearings.
AB  - BACKGROUND: Concerns have been raised about the sequelae of metal-on-metal (MoM)
      bearings in total hip arthroplasty (THA). However, retrieval studies, which offer
      the best insight into the clinically relevant mechanisms of MoM wear, have
      followed predictable trends to date such as indicting cobalt-chromium (CoCr)
      metallurgy, cup design, high conformity between the head and cup, "steep cups,"
      "microseparation," and "edge wear." QUESTIONS/PURPOSES: We wished to evaluate a
      set of retrieved 28-mm MoM THA for signs of (1) cup-to-stem impingement; (2)
      normal wear pattern and concomitant stripe damage on femoral heads that would
      signify adverse wear mechanics; and (3) well-defined evidence of third-body
      scratches on bearings that would indicate large abrasive particles had circulated
      the joint space. METHODS: Ten 28-mm MOM retrievals were selected on the basis
      that femoral stems were included. Revision surgeries at 3 to 8 years were for
      pain, osteolysis, and cup loosening. CoCr stems and the MoM bearings were
      produced by one vendor and Ti6Al4V stems by a second vendor. All but two cases
      had been fixed with bone cement. We looked for patterns of normal wear and
      impingement signs on femoral necks and cup rims. We looked for adverse wear
      defined as stripe damage that was visually apparent on each bearing. Wear
      patterns were examined microscopically to determine the nature of abrasions and
      signs of metal transfer. Graphical models recreated femoral neck and cup designs
      to precisely correlate impingement sites on femoral necks to cup positions and
      head stripe patterns. RESULTS: The evidence revealed that all CoCr cup liners had
      impinged on either anterior or posterior facets of femoral necks. Liner
      impingement at the most proximal neck notch occurred with the head well located
      and impingement at the distal notch occurred with the head rotated 5 mm out of
      the cup. The hip gained 20 degrees  motion by such a subluxation maneuver with
      this THA design. All heads had stripe wear, the basal and polar stripes
      coinciding with cup impingement sites. Analysis of stripe damage revealed 40 to
      100-MUm wide scratches created by large particles ploughing across bearing
      surfaces. The association of stripe wear with evidence of neck notching
      implicated impingement as the root cause, the outcome being the aggressive third
      body wear. CONCLUSIONS: We found consistent evidence of impingement, abnormal
      stripe damage, and evidence of third-body abrasive wear in a small sample of one
      type of 28-mm MoM design. Impingement models demonstrated that 28-mm heads could
      lever 20 degrees  out of the liners. Although other studies continue to show good
      success with 28-mm MoM bearings, their use has been discontinued at La Pitie
      Hospital.

PMID- 24297109
TI  - Editor's Spotlight/Take 5: Osteogenic gene expression correlates with development
      of heterotopic ossification in war wounds.

PMID- 24297110
TI  - The diagnostic utility of rib series in assessing rib fractures.
AB  - Rib series rarely add information to the posteroanterior (PA) film for the
      diagnosis of rib fractures. In this investigation, we evaluated the utility of
      rib X-rays using turnaround time (TAT), radiation exposure, and cost-efficiency
      as the key parameters. This investigation was conducted from January 2008 to
      December 2012. We included patients who had rib series performed for suspected
      rib fractures. TAT for patients was calculated from the time exam was ordered by
      the emergency department (ED) physician/staff to time the report was finalized by
      the attending radiologist. Effective radiation dose for rib series was calculated
      as a summation of radiation dose from the standard rib series images for each
      patient. Cost-efficiency was determined based on the number of interventions that
      took place as a result of a complicated study. Our investigation consisted of 422
      patients, 208 females aged (57 +/- 20.8) and 214 males aged (48 +/- 17.3). A
      total of 74(17.5 %) abnormal findings were noted, out of which only 1(0.23 %)
      underwent management change. The mean turnaround time for patients undergoing rib
      series had a value of 133.5 (+/-129.8) min as opposed to a single chest PA of
      61.8(+/- 64) min. Average effective radiation dose for a rib series was 0.105 (+/
      0.04) mSv, whereas average effective radiation dose of a single chest PA was 0.02
      mSv. Dedicated rib series has a low-yield diagnostic value as it pertains to
      management change. The overall impact on patient care based on our findings is
      small when compared to the risks associated with prolonged TAT, repeated exposure
      to radiation, and extensive medical costs.

PMID- 24297111
TI  - Effect of lipopolysaccharide on the characteristics of endothelial progenitor
      cells from bone marrow in mice.
AB  - Previous studies have shown that lipopolysaccharide (LPS) induces acute lung
      injury (ALI), and that endothelial progenitor cells (EPCs) participate in tissue
      repair. Therefore, in this study it was hypothesized that LPS influences the
      number and function of EPCs directly. In order to investigate this, an in vitro
      study was performed using EPCs. EPCs were cultured for seven days (early EPCs),
      and then treated with increasing concentrations of LPS (10 pg/ml, 100 pg/ml, 1
      ng/ml, 10 ng/ml and 100 ng/ml) for 4, 8, 12, and 24 h. The proliferation,
      senescence and adhesion of EPCs was then assessed. Alongside this an in vivo
      study was also performed. Mice were administered LPS (2.5 mg/kg) via the trachea.
      After 4, 8, 12, and 24 h, EPCs were harvested and cultured for seven days, and
      the proliferation, senescence and adhesion of the EPCs were examined. The results
      showed that the rate of adhesion and senescence of EPCs decreased in vitro when
      treated with 10 and 100 ng/ml LPS. The adhesion and senescence rate also
      decreased after 12 and 24 h in vivo. Proliferation, however, was increased in
      vitro following treatment with 10 and 100 ng/ml LPS, but proliferation in vivo
      decreased after 8 and 12 h. The effects of LPS on EPCs were distinct in vivo and
      in vitro. In vitro, cells were sensitive to 100 ng/ml LPS. In the course of ALI
      induced by LPS, the proliferation and adhesion activity of the EPCs was activated
      in 8 h and then gradually decreased with time.

PMID- 24297112
TI  - Oridonin induces apoptosis in SW1990 pancreatic cancer cells via p53- and caspase
      dependent induction of p38 MAPK.
AB  - Oridonin, an active component isolated from Rabdosia rubescens, has been reported
      to exhibit antitumor effects. In the present study, we evaluated the antitumor
      activity and the mechanisms of action of oridonin in pancreatic cancer. Oridonin
      treatment significantly induced apoptotic cell death in SW1990 pancreatic cancer
      cells in a dose-dependent manner. Additionally, cell apoptosis was markedly
      inhibited by PFT alpha (pifithrin alpha), a p53-specific inhibitor, which was
      applied to evaluate the function of p53, showing that p53 was responsible for the
      cytotoxity of oridonin. Moreover, oridonin increased the expression of p-p53 with
      a concomitant increase in p21 in the SW1990 cells. Following treatment with
      mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor),
      SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor), the cytotoxity of oridonin
      was not influenced by JNK (SP600125) and ERK (PD98059), but these effects were
      opposite to the cytotoxity of oridonin observed with SP203580 treatment. These
      findings confirmed that orodonin-induced apoptosis was p38-dependent, but JNK-
      and ERK-independent. Furthermore, the activation of the p38 kinase promoted the
      activation of p53 and its downstream target p21, and further caused caspase-9 and
      -3 activation, as demonstrated by evidence showing that the p38 inhibitor
      SB203580 not only blocked the phosphorylation of p38 but also reduced the
      activation of p53, p21 and caspase-9 and -3. Collectively, these results suggest
      that p53-dependent and caspase-dependent induction of p38 MAPK directly
      participates in apoptosis induced by oridonin.

PMID- 24297114
TI  - Set a short course but follow the patient's course for ventilator-associated
      pneumonia.

PMID- 24297113
TI  - Comparative multidimensional molecular analyses of pediatric diffuse intrinsic
      pontine glioma reveals distinct molecular subtypes.
AB  - Diffuse intrinsic pontine glioma (DIPG) is a highly morbid form of pediatric
      brainstem glioma. Here, we present the first comprehensive protein, mRNA, and
      methylation profiles of fresh-frozen DIPG specimens (n = 14), normal brain tissue
      (n = 10), and other pediatric brain tumors (n = 17). Protein profiling identified
      2,305 unique proteins indicating distinct DIPG protein expression patterns
      compared to other pediatric brain tumors. Western blot and immunohistochemistry
      validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1
      (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from
      tumor and adjacent normal brain tissue indicated two DIPG subgroups,
      characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We
      validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway,
      in a subgroup of DIPG specimens. DNA methylation analysis indicated global
      hypomethylation of DIPG compared to adjacent normal tissue specimens, with
      differential methylation of 24 genes involved in Hh and Myc pathways, correlating
      with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T
      mutations in the H3F3A or HIST1H3B gene in 77 % of our DIPG cohort. Supervised
      analysis revealed a unique methylation pattern in mutated specimens compared to
      the wild-type DIPG samples. This study presents the first comprehensive
      multidimensional protein, mRNA, and methylation profiling of pediatric brain
      tumor specimens, detecting the presence of two subgroups within our DIPG cohort.
      This multidimensional analysis of DIPG provides increased analytical power to
      more fully explore molecular signatures of DIPGs, with implications for
      evaluating potential molecular subtypes and biomarker discovery for assessing
      response to therapy. 

PMID- 24297115
TI  - Simultaneously diagnosing and staging lung cancer: a win-win for the patient and
      the health-care system.

PMID- 24297116
TI  - Framing discussions about CT scan screening for lung cancer so that patients see
      the whole picture.

PMID- 24297118
TI  - Point: should board certification in sleep be required to prescribe CPAP therapy
      on the basis of home sleep testing? Yes.

PMID- 24297119
TI  - Counterpoint: should board certification in sleep be required to prescribe CPAP
      therapy on the basis of home sleep testing? No.

PMID- 24297120
TI  - Rebuttal from Dr. Brown.

PMID- 24297121
TI  - Rebuttal from Dr. Gay.

PMID- 24297122
TI  - Epithelial injury and repair in airways diseases.
AB  - Asthma is a common chronic disease characterized by variable respiratory distress
      with underlying airway inflammation and airflow obstruction. The incidence of
      asthma has risen inexorably over the past 50 years, suggesting that environmental
      factors are important in its etiology. All inhaled environmental stimuli interact
      with the lung at the respiratory epithelium, and it is a testament to the
      effectiveness of the airway innate defenses that the majority of inhaled
      substances are cleared without the need to elicit an inflammatory response.
      However, once this barrier is breached, effective communication with immune and
      inflammatory cells is required to protect the internal milieu of the lung. In
      asthma, the respiratory epithelium is known to be structurally and functionally
      abnormal. Structurally, the epithelium shows evidence of damage and has more
      mucus-producing cells than normal airways. Functionally, the airway epithelial
      barrier can be more permeable and more sensitive to oxidants and show a deficient
      innate immune response to respiratory virus infection compared with that in
      normal individuals. The potential of a susceptible epithelium and the underlying
      mesenchyme to create a microenvironment that enables deviation of immune and
      inflammatory responses to external stimuli may be crucial in the development and
      progression of asthma. In this review, we consider three important groups of
      environmental stimuli on the epithelium in asthma: oxidants, such as
      environmental pollution and acetaminophen; viruses, including rhinovirus; and
      agents that cause barrier disruption, such as house dust mite allergens. The
      pathology associated with each stimulus is considered, and potential future
      treatments arising from research on their effects are presented. 

PMID- 24297123
TI  - An update on pulmonary complications of hematopoietic stem cell transplantation.
AB  - The indications for hematopoietic stem cell transplantation (HSCT) continue to
      expand. However, the risk for pulmonary complications post-HSCT continues to be
      high. Early recognition and treatment of pulmonary complications may improve
      outcomes. This is an overview of diagnosis, manifestations, and treatment of the
      most common infectious and noninfectious pulmonary complications post-HSCT.
      Knowing the patient's timeframe post-HSCT (preengraftment, postengraftment,
      late), type of HSCT (allogeneic vs autologous), radiographic findings, and
      clinical presentation can help to differentiate between the many pulmonary
      complications. This article will also address pretransplantation evaluation and
      infectious and noninfectious complications in the patient post-HSCT. While
      mortality post-HSCT continues to improve, respiratory failure continues to be the
      leading cause of ICU admissions for patients who have undergone HSCT. Mechanical
      ventilation is a predictor of poor outcomes in these patients, and further
      research is needed regarding their critical care management, treatment options
      for noninfectious pulmonary complications, and mortality prediction models
      posttransplantation. 

PMID- 24297124
TI  - alpha1-antitrypsin deficiency: what has it ever done for us?
AB  - The first five cases of alpha1-antitrypsin deficiency were originally published
      in 1963. This changed our whole concept about the pathophysiology of emphysema,
      including the role of inflammation and, in particular, the role of proteolytic
      enzymes. However, the observation also had a significant 50-year impact on many
      aspects of protein biochemistry, genetics, cell biology, and disease concepts
      outside the lung as well as the study of COPD in general. 

PMID- 24297125
TI  - Taking control of your digital library: how modern citation managers do more than
      just referencing.
AB  - Physicians are constantly navigating the overwhelming body of medical literature
      available on the Internet. Although early citation managers were capable of
      limited searching of index databases and tedious bibliography production, modern
      versions of citation managers such as EndNote, Zotero, and Mendeley are powerful
      web-based tools for searching, organizing, and sharing medical literature.
      Effortless point-and-click functions provide physicians with the ability to
      develop robust digital libraries filled with literature relevant to their fields
      of interest. In addition to easily creating manuscript bibliographies, various
      citation managers allow physicians to readily access medical literature, share
      references for teaching purposes, collaborate with colleagues, and even
      participate in social networking. If physicians are willing to invest the time to
      familiarize themselves with modern citation managers, they will reap great
      benefits in the future. 

PMID- 24297126
TI  - Successful polymyxin B hemoperfusion treatment associated with serial reduction
      of serum anti-CADM-140/MDA5 antibody levels in rapidly progressive interstitial
      lung disease with amyopathic dermatomyositis.
AB  - Clinically amyopathic dermatomyositis (CADM), a subtype of dermatomyositis with
      subtle or no muscle involvement, is occasionally accompanied by fatal, rapidly
      progressive interstitial lung disease (RP-ILD) that is resistant to aggressive
      immunosuppressive therapy. The presence of anti-CADM-140/MDA5 antibodies is
      diagnostic for patients with dermatomyositis (particularly CADM) and is known to
      be strongly associated with the pathogenesis, disease activity, and mortality of
      RP-ILD. Polymyxin-B direct hemoperfusion (PMX-DHP), originally developed for the
      removal of endotoxin, has been demonstrated to be effective for treating various
      types of acute respiratory failure. We describe a patient with amyopathic
      dermatomyositis who developed RP-ILD characterized by elevated anti-CADM-140/MDA5
      autoantibodies, was resistant to combined steroid and immunosuppressant therapy,
      and was treated successfully with PMX-DHP. To our knowledge, this is the first
      case to indicate a serial reduction of anti-CADM-140/MDA5 autoantibodies,
      associated with clinical improvement, following PMX-DHP. Early intervention using
      PMX-DHP may improve the prognosis of RP-ILD accompanied by CADM. 

PMID- 24297127
TI  - Octreotide: a drug often used in the critical care setting but not well
      understood.
AB  - While the canonical function of somatostatin (SST) is to inhibit the secretion of
      growth hormone, it has a number of other physiologic effects that are less widely
      appreciated. Octreotide, an analog of SST, is not uncommonly used in the critical
      care setting, particularly for the treatment of variceal hemorrhage. Herein, we
      discuss the biology and pharmacology of SST, octreotide, and other SST analogs.
      We also review the evidence behind their use in esophageal variceal bleeds,
      hepatorenal syndrome, hypoglycemia due to sulfonylurea poisoning, and chylous
      pleural effusions. 

PMID- 24297128
TI  - Novel and emerging nonpositive airway pressure therapies for sleep apnea.
AB  - CPAP therapy has remained the standard of care for the treatment of sleep apnea
      for nearly 4 decades. Its overall effectiveness, however, has been limited by
      incomplete adherence despite many efforts to improve comfort. Conventional
      alternative therapies include oral appliances and upper airway surgeries.
      Recently, several innovative alternatives to CPAP have been developed. These
      novel approaches include means to increase arousal thresholds, electrical nerve
      stimulation, oral vacuum devices, and nasal expiratory resistive devices. We will
      review the physiologic mechanisms and the current evidence for these novel
      treatments. 

PMID- 24297129
TI  - Rare condition of giant deformities in ribs resulting in significant dyspnea.

PMID- 24297130
TI  - A 39-year-old male slaughterhouse worker with recurrent fever, cough, and
      shortness of breath.

PMID- 24297131
TI  - A 32-year-old woman with dyspnea, lung cysts, and previous pneumothoraces.

PMID- 24297134
TI  - Does miR-1 play a role in malignant pleural mesothelioma development and
      progression?

PMID- 24297135
TI  - Response.

PMID- 24297136
TI  - Autotitrating positive airway pressure therapy in OSA.

PMID- 24297137
TI  - Response.

PMID- 24297138
TI  - Diagnostic and statistical manual of mental disorders, fifth edition, and the
      impact of events scale-revised.

PMID- 24297139
TI  - Response.

PMID- 24297140
TI  - Physical activity vs psychomotor activity: prognostication of COPD.

PMID- 24297141
TI  - Predicting community-acquired pneumonia etiology.

PMID- 24297142
TI  - Response.

PMID- 24297143
TI  - Sarcoidosis, fatigue, and sleep apnea.

PMID- 24297144
TI  - Response.

PMID- 24297145
TI  - Airways disease presenting as restrictive impairment: a variant in asthma, a
      defining feature in world trade center lung disorder.

PMID- 24297146
TI  - Response.

PMID- 24297147
TI  - Thrombocytopenia and thromboprophylaxis: a difficult combination?

PMID- 24297148
TI  - Response.

PMID- 24297150
TI  - A patient with acute COPD exacerbation and shock.

PMID- 24297151
TI  - Circulating melanoma cells in the diagnosis and monitoring of melanoma: an
      appraisal of clinical potential.
AB  - Circulating melanoma cells (CMCs) are thought to be the foundation for metastatic
      disease, which makes this cancer especially lethal. Cancer cells contained in the
      primary tumor undergo genotypic and phenotypic changes leading to an epithelial
      to-mesenchymal transition, during which numerous changes occur in signaling
      pathways and proteins in the cells. CMCs are then shed off or migrate from the
      primary tumor and intravasate the vasculature system. A few CMCs are able to
      survive in the circulation through expression of a variety of genes and also by
      evading immune system recognition to establish metastases at distant sites after
      extravasating from the vessels. The presence of CMCs in the blood of a melanoma
      patient can be used for disease staging, predicting metastasis development, and
      evaluating the efficacy of therapeutic agents. Overall survival and disease-free
      duration can also be correlated with the presence of CMCs. Finally, analysis of
      CMCs for druggable therapeutic gene targets could lead to the development of
      personalized treatment regimens to prevent metastasis. Thus, the study of CMCs
      shows promise for the detection, staging, and monitoring of disease treatment, as
      well as for determination of prognosis and predicting overall disease-free
      survival. These are the areas reviewed in this article. 

PMID- 24297152
TI  - A rationalized approach to the treatment of patients infected with hepatitis B.
AB  - It is estimated that there are 350-400 million individuals with chronic hepatitis
      B virus infection (HBV) worldwide. The natural course of HBV infection is
      variable with a number of individuals developing no or only mild disease, while
      others will die from liver-associated complications if left untreated. It is
      estimated that 25% of individuals with HBV infection will eventually die from the
      complications of HBV-associated liver disease. Several viral and host variables
      including hepatitis B e antigen status, HBV genotype, viral load, hepatitis B
      surface antigen and transaminase levels, and viral mutations have been identified
      as determinants of disease outcomes. The personalized approach to the treatment
      of chronic hepatitis B might include mere monitoring of the disease in some
      patients but aggressive treatment in others. Individuals who require treatment
      should have close monitoring to help ensure maximum medication compliance, to
      watch for adverse events, and to monitor virologic and biochemical responses.
      Therefore, management of patients with chronic HBV infection requires a practical
      setting to demonstrate the relevance of personalized medicine, the roles and
      limitations of genetic and non-genetic factors, and the risks and benefits of
      individualized patient care. This article provides an overview of the viral and
      host genetics of chronic HBV and reviews the clinical utility of serum
      quantitative hepatitis B surface antigen in the management of patients with
      chronic HBV infection.

PMID- 24297153
TI  - White matter injury induced by perinatal exposure to glutaric acid.
AB  - Glutaric acid (GA) is a neurotoxic metabolite that accumulates in the CNS of
      patients with glutaric acidemia-I (GA-I), a neurometabolic disease caused by
      deficient activity of glutaryl-CoA dehydrogenase. Most GA-I patients display
      characteristic CNS lesions, mainly in the gray and white matter of basal ganglia
      and cerebral cortex. Neurons and astrocytes are believed to be vulnerable to
      millimolar concentrations of GA. However, little is known about the effects of GA
      on oligodendrocytes (OL) and the myelination process in the postnatal brain.
      Here, we show that a single intracerebroventricular administration of GA to rat
      neonatal pups induced a selective and long-lasting myelination failure in the
      striatum but no deleterious effect in the myelination of the corpus callosum. At
      45 days post-GA injection, the myelinated area of striatal axonal bundles was
      decreased by 35 %, and the expression of myelin basic protein and myelin
      associated glycoprotein (MAG) reduced by 25 and 60 %, respectively. This was
      accompanied by long lasting cytopathology features in MAG and CC-1-expressing
      OLs, which was confirmed by transmission electron microscopy. Remarkably, GA did
      not induce acute loss of pre-OLs in the striatum as assessed by NG2 or PDGFRalpha
      immunohistochemistry, suggesting an indirect and progressive mechanism for OL
      damage. In accordance, GA-induced white matter injury was restricted to the
      striatum and associated to GA-induced astrocytosis and neuronal loss. In
      conclusion, the current evidence indicates a pathogenic mechanism by which GA can
      permanently affect myelin status.

PMID- 24297155
TI  - Genotoxic mixtures and dissimilar action: concepts for prediction and assessment.
AB  - Combinations of genotoxic agents have frequently been assessed without clear
      assumptions regarding their expected (additive) mixture effects, often leading to
      claims of synergisms that might in fact be compatible with additivity. We have
      shown earlier that the combined effects of chemicals, which induce micronuclei
      (MN) in the cytokinesis-block micronucleus assay in Chinese hamster ovary-K1
      cells by a similar mechanism, were additive according to the concept of
      concentration addition (CA). Here, we extended these studies and investigated for
      the first time whether valid additivity expectations can be formulated for MN
      inducing chemicals that operate through a variety of mechanisms, including
      aneugens and clastogens (DNA cross-linkers, topoisomerase II inhibitors, minor
      groove binders). We expected that their effects should follow the additivity
      principles of independent action (IA). With two mixtures, one composed of various
      aneugens (colchicine, flubendazole, vinblastine sulphate, griseofulvin,
      paclitaxel), and another composed of aneugens and clastogens (flubendazole,
      doxorubicin, etoposide, melphalan and mitomycin C), we observed mixture effects
      that fell between the additivity predictions derived from CA and IA. We achieved
      better agreement between observation and prediction by grouping the chemicals
      into common assessment groups and using hybrid CA/IA prediction models. The
      combined effects of four dissimilarly acting compounds (flubendazole, paclitaxel,
      doxorubicin and melphalan) also fell within CA and IA. Two binary mixtures
      (flubendazole/paclitaxel and flubendazole/doxorubicin) showed effects in
      reasonable agreement with IA additivity. Our studies provide a systematic basis
      for the investigation of mixtures that affect endpoints of relevance to
      genotoxicity and show that their effects are largely additive.

PMID- 24297156
TI  - Cascade iatrogenesis: a case-control study to detect postoperative respiratory
      failure in hospitalized older adults.
AB  - During hospitalization, older adults are at high risk for cascade iatrogenesis,
      the serial development of complications. In this retrospective, descriptive, case
      control pilot study, 28 patients (cases) who developed respiratory failure after
      an elective surgical procedure were compared to 28 matched controls who did not
      develop postoperative respiratory failure. The type, frequency, and timing of
      events that preceded the development of postoperative respiratory failure in
      hospitalized older adults (age 65 and older) and the presence and timing of
      similar events for matched controls during a postoperative period of the same
      length were recorded. Cases experienced certain trigger events, including
      atelectasis and fluid overload, at significantly higher rates than controls.
      Cases and controls experienced similar rates of oversedation and delirium, yet
      controls were less likely to aspirate following these episodes. Patients who
      developed postoperative respiratory failure were less likely to ambulate early
      and experienced more calls to rapid response or code teams, more transfers to
      higher levels of care, longer lengths of stay, and more deaths than matched
      controls.

PMID- 24297157
TI  - On the lithiation reaction of niobium oxide: structural and electronic properties
      of Li(1.714)Nb2O5.
AB  - Monoclinic alpha-Nb2O5 was chemically lithiated by reaction with n-butyllithium,
      mimicking the product of electrochemical discharge of a niobium oxide cathode vs.
      a Li anode. The compound was investigated by neutron powder diffraction (D2B
      equipment at ILL, France) and its structure was Rietveld refined in space group
      P2 to wRp = 0.045, locating the Li atoms inserted in the alpha-Nb2O5 framework.
      The ensuing chemical formula is Li12/7Nb2O5. Some Li atoms are more strongly
      bonded (five coordinated O atoms), some are less strongly bonded (coordination
      number = 4). Starting from the experimental structure, first-principles periodic
      DFT calculations based on the hybrid B3LYP functional were performed. The
      electrochemical voltage of Li insertion was computed to be 1.67 V, fully
      consistent with the experimental 1.60 V plateau vs. capacity. The analysis of the
      electron band structure shows that lithiation changes the insulating oxide into a
      semi-metal; some of the extra electrons inserted with lithium become spin
      polarized and give the material weak ferromagnetic properties. 

PMID- 24297158
TI  - Production of thermo-alkali-stable xylanase by a novel polyextremophilic Bacillus
      halodurans TSEV1 in cane molasses medium and its applicability in making whole
      wheat bread.
AB  - A high titre of thermo-alkali-stable xylanase was attained in cane molasses
      medium. When the culture variables for endoxylanase production were optimized
      [cane molasses 7 %, soluble alkaline extract of wheat bran (SAE-WB) 37 % and
      ammonium chloride 0.30 %], a 4.5-fold enhancement in xylanase production (69 U
      ml(-1)) was achieved as compared to that in the unoptimized medium (15 U ml(-1)).
      The enzyme titre attained in shake flasks could be sustained in a 7-l laboratory
      bioreactor. An activity band corresponding to 40 kDa was visualized on SDS-PAGE
      zymogram analysis. The enzyme has broad range of pH and temperature for activity
      with optima at 9.0 and 80  degrees C, and stable between pH 4.0 and 11.0 with 85
      % retention of activity. It has T 1/2 of 40 and 15 min at 70 and 80  degrees C.
      The enzyme is halotolerant since it displays activity in the presence of salt up
      to 15 %, and remains 100 % active in the absence of salt. The supplementation of
      whole wheat dough with xylanase improves antistaling property, reducing sugar
      content, bread volume with prebiotic xylooligosaccharides in bread. This is the
      first report on xylanase production in cane molasses medium with SAE-WB as the
      inducer and its applicability in whole wheat bread making that improves human
      health.

PMID- 24297159
TI  - High-rate partial nitritation using porous poly(vinyl alcohol) sponge.
AB  - Poly(vinyl alcohol) (PVA) has been utilized as a support material for the
      immobilization of nitrifying bacteria without the comprehensive survey of partial
      nitritation. In the present study, the activities of nitrifiers and the maximum
      nitrogen conversion rate of partial nitritation with PVA sponge-cubes were
      specified according to different conditions. The selective enrichment of ammonia
      oxidizing bacteria (AOB) on PVA sponge-cubes was achieved by the competition
      between AOB and nitrite-oxidizing bacteria for dissolved oxygen. The efficiency
      of ammonia oxidation was proportional to the concentration of HCO3 (-) with the
      molar ratio of HCO3 (-)-C/NH4 (+)-N = 1.91 and a half of the ratio was applied to
      the further experiments to ensure stable partial nitritation. The maximum
      nitrogen conversion rate of partial nitritation was dependent on the volume, not
      the size of sponge-cubes. The partial nitritation showed the superior rate
      performance of 3.09 kg N/m(3) day with the packing ratio of 32 % of 5 * 5 * 5
      mm(3) PVA sponge-cubes.

PMID- 24297160
TI  - Epigallocatechin-3-gallate-capped Ag nanoparticles: preparation and
      characterization.
AB  - We used an aqueous leaf extract of Camellia sinensis to synthesize Ag
      nanoparticles (AgNPs). A layer of ca. 6 nm around a group of the AgNPs in which
      the inner layer is bound to the AgNPs surface via the hydroxyl groups of catechin
      has been observed. TEM analysis of AgNPs showed the formation of truncated
      triangular nanoplates and/or nanodisks and spherical with some irregular-shaped
      polydispersed nanoparticles in absence and presence of shape-directing
      cetyltrimethylammonium bromide. The polyphenolic groups of epigallocatechin-3
      gallate (EGCG) are responsible for the rapid reduction of Ag(+) ions into
      metallic Ag(0). The free -OH groups are able to stabilize AgNPs by the
      interaction between the surface Ag atoms of AgNPs and oxygen atoms of EGCG
      molecules.

PMID- 24297162
TI  - Direct modification of colloidal hole-masks for locally ordered hetero-assemblies
      of nanostructures over large areas.
AB  - We have developed a direct mask modification method applicable in hole-mask
      nanostructure fabrication. It is demonstrated that by using this technique the
      size, material, relative location and ordering of individual subunits can be
      controlled and varied independently to generate hetero-assemblies of
      nanostructures including chiral structures over large areas. 

PMID- 24297161
TI  - Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain
      tumors.
AB  - BACKGROUND: Recurrent malignant brain tumors (RMBTs) carry a poor prognosis.
      Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown
      activity against several human cancers. DESIGN: We conducted an open-label study
      of oral DCA in 15 adults with recurrent WHO grade III - IV gliomas or metastases
      from a primary cancer outside the central nervous system. The primary objective
      was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment,
      defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable
      to DCA, based on the National Cancer Institute's Common Toxicity Criteria for
      Adverse Events, version 4.0. Secondary objectives involved safety, tolerability
      and hypothesis-generating data on disease status. Dosing was based on haplotype
      variation in glutathione transferase zeta 1/maleylacetoacetate isomerase
      (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. RESULTS: Eight
      patients completed at least 1 four week cycle. During this time, no dose-limiting
      toxicities occurred. No patient withdrew because of lack of tolerance to DCA,
      although 2 subjects experienced grade 0-1 distal parasthesias that led to
      elective withdrawal and/or dose-adjustment. All subjects completing at least 1
      four week cycle remained clinically stable during this time and remained on DCA
      for an average of 75.5 days (range 26-312). CONCLUSIONS: Chronic, oral DCA is
      feasible and well-tolerated in patients with recurrent malignant gliomas and
      other tumors metastatic to the brain using the dose range established for
      metabolic diseases. The importance of genetic-based dosing is confirmed and
      should be incorporated into future trials of chronic DCA administration.

PMID- 24297163
TI  - Regulation of protease-activated receptor 1 signaling by the adaptor protein
      complex 2 and R4 subfamily of regulator of G protein signaling proteins.
AB  - The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly
      proteolytically activated by thrombin. Hence, the precise regulation of PAR1
      signaling is important for proper cellular responses. In addition to
      desensitization, internalization and lysosomal sorting of activated PAR1 are
      critical for the termination of signaling. Unlike most G protein-coupled
      receptors, PAR1 internalization is mediated by the clathrin adaptor protein
      complex 2 (AP-2) and epsin-1, rather than beta-arrestins. However, the function
      of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we
      report that AP-2, and not epsin-1, regulates activated PAR1-stimulated
      phosphoinositide hydrolysis via two different mechanisms that involve, in part, a
      subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A
      significantly greater increase in activated PAR1 signaling was observed in cells
      depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant
      with defective AP-2 binding. This effect was attributed to AP-2 modulation of
      PAR1 surface expression and efficiency of G protein coupling. We further found
      that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5
      reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA
      mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis
      revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type
      but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the
      AKKAA mutant, induced Galphaq association with RGS3 via an AP-2-dependent
      mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor
      surface expression and through recruitment of RGS proteins. 

PMID- 24297164
TI  - Cuz1/Ynl155w, a zinc-dependent ubiquitin-binding protein, protects cells from
      metalloid-induced proteotoxicity.
AB  - Protein misfolding is a universal threat to cells. The ubiquitin-proteasome
      system mediates a cellular stress response capable of eliminating misfolded
      proteins. Here we identify Cuz1/Ynl155w as a component of the ubiquitin system,
      capable of interacting with both the proteasome and Cdc48. Cuz1/Ynl155w is
      regulated by the transcription factor Rpn4, and is required for cells to survive
      exposure to the trivalent metalloids arsenic and antimony. A related protein,
      Yor052c, shows similar phenotypes, suggesting a multicomponent stress response
      pathway. Cuz1/Ynl155w functions as a zinc-dependent ubiquitin-binding protein.
      Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced
      proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome
      for destruction. 

PMID- 24297165
TI  - Functional evaluation of activation-dependent alterations in the sialoglycan
      composition of T cells.
AB  - Sialic acids (Sias) are often conjugated to the termini of cellular glycans and
      are key mediators of cellular recognition. Sias are nine-carbon acidic sugars,
      and, in vertebrates, the major species are N-acetylneuraminic acid (Neu5Ac) and N
      glycolylneuraminic acid (Neu5Gc), differing in structure at the C5 position.
      Previously, we described a positive feedback loop involving regulation of Neu5Gc
      expression in mouse B cells. In this context, Neu5Gc negatively regulated B-cell
      proliferation, and Neu5Gc expression was suppressed upon activation. Similarly,
      resting mouse T cells expressed principally Neu5Gc, and Neu5Ac was induced upon
      activation. In the present work, we used various probes to examine sialoglycan
      expression by activated T cells in terms of the Sia species expressed and the
      linkages of Sias to glycans. Upon T-cell activation, sialoglycan expression
      shifted from Neu5Gc to Neu5Ac, and the linkage shifted from alpha2,6 to alpha2,3.
      These changes altered the expression levels of sialic acid-binding immunoglobulin
      like lectin (siglec) ligands. Expression of sialoadhesin and Siglec-F ligands
      increased, and that of CD22 ligands decreased. Neu5Gc exerted a negative effect
      on T-cell activation, both in terms of the proliferative response and in the
      context of activation marker expression. Suppression of Neu5Gc expression in
      mouse T and B cells prevented the development of nonspecific CD22-mediated T cell
      B cell interactions. Our results suggest that an activation-dependent shift from
      Neu5Gc to Neu5Ac and replacement of alpha2,6 by alpha2,3 linkages may regulate
      immune cell interactions at several levels. 

PMID- 24297166
TI  - Residues in the polar loop of subunit c in Escherichia coli ATP synthase function
      in gating proton transport to the cytoplasm.
AB  - Rotary catalysis in F1F0 ATP synthase is powered by proton translocation through
      the membrane-embedded F0 sector. Proton binding and release occur in the middle
      of the membrane at Asp-61 on the second transmembrane helix (TMH) of subunit c,
      which folds in a hairpin-like structure with two TMHs. Previously, the aqueous
      accessibility of Cys substitutions in the transmembrane regions of subunit c was
      probed by testing the inhibitory effects of Ag(+) or Cd(2+) on function, which
      revealed extensive aqueous access in the region around Asp-61 and on the half of
      TMH2 extending to the cytoplasm. In the current study, we surveyed the Ag(+) and
      Cd(2+) sensitivity of Cys substitutions in the loop of the helical hairpin and
      used a variety of assays to categorize the mechanisms by which Ag(+) or Cd(2+)
      chelation with the Cys thiolates caused inhibition. We identified two distinct
      metal-sensitive regions in the cytoplasmic loop where function was inhibited by
      different mechanisms. Metal binding to Cys substitutions in the N-terminal half
      of the loop resulted in an uncoupling of F1 from F0 with release of F1 from the
      membrane. In contrast, substitutions in the C-terminal half of the loop retained
      membrane-bound F1 after metal treatment. In several of these cases, inhibition
      was shown to be due to blockage of passive H(+) translocation through F0 as
      assayed with F0 reconstituted into liposomes. The results suggest that the C
      terminal domain of the cytoplasmic loop may function in gating H(+) translocation
      to the cytoplasm. 

PMID- 24297167
TI  - Differential role of Snail1 and Snail2 zinc fingers in E-cadherin repression and
      epithelial to mesenchymal transition.
AB  - Snail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar
      DNA binding structure of four and five C2H2 zinc finger motifs (ZF),
      respectively. Both factors bind specifically to a subset of E-box motifs (E2-box:
      CAGGTG/CACCTG) in target promoters like the E-cadherin promoter and are key
      mediators of epithelial-to-mesenchymal transition (EMT). However, there are
      differences in the biological actions, in binding affinities to E-cadherin
      promoter, and in the target genes of Snail1 and Snail2, although the molecular
      bases are presently unknown. In particular, the role of each Snail1 and Snail2 ZF
      in the binding to E-boxes and in EMT induction has not been previously explored.
      We have approached this question by modeling Snail1 and Snail2 protein-DNA
      interactions and through mutational and functional assays of different ZFs.
      Results show that Snail1 efficient repression and binding to human and mouse E
      cadherin promoter as well as EMT-inducing ability require intact ZF1 and ZF2,
      while for Snail2, either ZF3 or ZF4 is essential for those functions.
      Furthermore, the differential distribution of E2-boxes in mouse and human E
      cadherin promoters also contributes to the differential Snail factor activity.
      These data indicate a non-equivalent role of Snail1 and Snail2 ZFs in gene
      repression, contributing to the elucidation of the molecular differences between
      these important EMT regulators. 

PMID- 24297168
TI  - ADP-dependent conformational changes distinguish Mycobacterium tuberculosis SecA2
      from SecA1.
AB  - In bacteria, most secreted proteins are exported through the SecYEG translocon by
      the SecA ATPase motor via the general secretion or "Sec" pathway. The
      identification of an additional SecA protein, particularly in Gram-positive
      pathogens, has raised important questions about the role of SecA2 in both protein
      export and establishment of virulence. We previously showed in Mycobacterium
      tuberculosis, the causative agent of tuberculosis, the accessory SecA2 protein
      possesses ATPase activity that is required for bacterial survival in host
      macrophages, highlighting its importance in virulence. Here, we show that SecA2
      binds ADP with much higher affinity than SecA1 and releases the nucleotide more
      slowly. Nucleotide binding also regulates movement of the precursor-binding
      domain in SecA2, unlike in SecA1 or conventional SecA proteins. This
      conformational change involving closure of the clamp in SecA2 may provide a
      mechanism for the cell to direct protein export through the conventional SecA1
      pathway under normal growth conditions while preventing ordinary precursor
      proteins from interacting with the specialized SecA2 ATPase. 

PMID- 24297169
TI  - Membrane and chaperone recognition by the major translocator protein PopB of the
      type III secretion system of Pseudomonas aeruginosa.
AB  - The type III secretion system is a widespread apparatus used by pathogenic
      bacteria to inject effectors directly into the cytoplasm of eukaryotic cells. A
      key component of this highly conserved system is the translocon, a pore formed in
      the host membrane that is essential for toxins to bypass this last physical
      barrier. In Pseudomonas aeruginosa the translocon is composed of PopB and PopD,
      both of which before secretion are stabilized within the bacterial cytoplasm by a
      common chaperone, PcrH. In this work we characterize PopB, the major
      translocator, in both membrane-associated and PcrH-bound forms. By combining
      sucrose gradient centrifugation experiments, limited proteolysis, one-dimensional
      NMR, and beta-lactamase reporter assays on eukaryotic cells, we show that PopB is
      stably inserted into bilayers with its flexible N-terminal domain and C-terminal
      tail exposed to the outside. In addition, we also report the crystal structure of
      the complex between PcrH and an N-terminal region of PopB (residues 51-59), which
      reveals that PopB lies within the concave face of PcrH, employing mostly backbone
      residues for contact. PcrH is thus the first chaperone whose structure has been
      solved in complex with both type III secretion systems translocators, revealing
      that both molecules employ the same surface for binding and excluding the
      possibility of formation of a ternary complex. The characterization of the major
      type III secretion system translocon component in both membrane-bound and
      chaperone-bound forms is a key step for the eventual development of
      antibacterials that block translocon assembly. 

PMID- 24297170
TI  - Understanding how the complex molecular architecture of mannan-degrading
      hydrolases contributes to plant cell wall degradation.
AB  - Microbial degradation of plant cell walls is a central component of the carbon
      cycle and is of increasing importance in environmentally significant industries.
      Plant cell wall-degrading enzymes have a complex molecular architecture
      consisting of catalytic modules and, frequently, multiple non-catalytic
      carbohydrate binding modules (CBMs). It is currently unclear whether the
      specificities of the CBMs or the topology of the catalytic modules are the
      primary drivers for the specificity of these enzymes against plant cell walls.
      Here, we have evaluated the relationship between CBM specificity and their
      capacity to enhance the activity of GH5 and GH26 mannanases and CE2 esterases
      against intact plant cell walls. The data show that cellulose and mannan binding
      CBMs have the greatest impact on the removal of mannan from tobacco and
      Physcomitrella cell walls, respectively. Although the action of the GH5 mannanase
      was independent of the context of mannan in tobacco cell walls, a significant
      proportion of the polysaccharide was inaccessible to the GH26 enzyme. The
      recalcitrant mannan, however, was fully accessible to the GH26 mannanase appended
      to a cellulose binding CBM. Although CE2 esterases display similar specificities
      against acetylated substrates in vitro, only CjCE2C was active against acetylated
      mannan in Physcomitrella. Appending a mannan binding CBM27 to CjCE2C potentiated
      its activity against Physcomitrella walls, whereas a xylan binding CBM reduced
      the capacity of esterases to deacetylate xylan in tobacco walls. This work
      provides insight into the biological significance for the complex array of
      hydrolytic enzymes expressed by plant cell wall-degrading microorganisms. 

PMID- 24297171
TI  - The role of collagen charge clusters in the modulation of matrix
      metalloproteinase activity.
AB  - Members of the matrix metalloproteinase (MMP) family selectively cleave collagens
      in vivo. Several substrate structural features that direct MMP collagenolysis
      have been identified. The present study evaluated the role of charged residue
      clusters in the regulation of MMP collagenolysis. A series of 10 triple-helical
      peptide (THP) substrates were constructed in which either Lys-Gly-Asp or Gly-Asp
      Lys motifs replaced Gly-Pro-Hyp (where Hyp is 4-hydroxy-L-proline) repeats. The
      stabilities of THPs containing the two different motifs were analyzed, and
      kinetic parameters for substrate hydrolysis by six MMPs were determined. A
      general trend for virtually all enzymes was that, as Gly-Asp-Lys motifs were
      moved from the extreme N and C termini to the interior next to the cleavage site
      sequence, kcat/Km values increased. Additionally, all Gly-Asp-Lys THPs were as
      good or better substrates than the parent THP in which Gly-Asp-Lys was not
      present. In turn, the Lys-Gly-Asp THPs were also always better substrates than
      the parent THP, but the magnitude of the difference was considerably less
      compared with the Gly-Asp-Lys series. Of the MMPs tested, MMP-2 and MMP-9 most
      greatly favored the presence of charged residues with preference for the Gly-Asp
      Lys series. Lys-Gly-(Asp/Glu) motifs are more commonly found near potential MMP
      cleavage sites than Gly-(Asp/Glu)-Lys motifs. As Lys-Gly-Asp is not as favored by
      MMPs as Gly-Asp-Lys, the Lys-Gly-Asp motif appears advantageous over the Gly-Asp
      Lys motif by preventing unwanted MMP hydrolysis. More specifically, the lack of
      Gly-Asp-Lys clusters may diminish potential MMP-2 and MMP-9 collagenolytic
      activity. The present study indicates that MMPs have interactions spanning the
      P23-P23' subsites of collagenous substrates.

PMID- 24297172
TI  - The evidence of HeLa cell apoptosis induced with tetraethylammonium using
      proteomics and various analytical methods.
AB  - Tetraethylammonium (TEA) is a potassium channel (KCh) blocker applied in the
      functional and pharmacological studies of the KChs. The MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, a colorimetric
      assay to quantitatively measure living cells, demonstrated that TEA reduced the
      HeLa cell viability dose-dependently. Flow cytometry analysis indicated an
      increased apoptosis rate of the HeLa cell after exposing to TEA. The patch clamp
      technique revealed that the K(+) current of the HeLa cell was inhibited up to 80%
      when exposed to TEA. In addition, quantitative real-time PCR approach set up
      cross-talk among the cytotoxicity of TEA, 4-aminopyridine, and anti-cancer drug
      such as cisplatin. Using comparative proteomics combined with MALDI-TOF MS/MS, 33
      significantly changed proteins were found from TEA treatment group; among these
      proteins, 12 were up-regulated, and 21 were down-regulated. Here we indicated
      that these proteins were closely connected with many biological functions such as
      oxidative stress response, signal transduction, metabolism, protein synthesis,
      and degradation. Both Western blotting and quantitative real-time PCR approaches
      further verified these differential proteins. Ingenuity Pathways Analysis
      software, a tool to analyze "omics" data and model biological system, was applied
      to analyze the interaction pathways of these proteins. The subcellular locations
      of the differential proteins are also predicted from Uniprot. All results above
      can help in our understanding of the mechanism of TEA-induced cytotoxicity and
      provide potential cancer biomarkers. Various experimental results in this study
      (like those for cisplatin) indicated that TEA is not only a KCh blocker but also
      a potential anti-cancer drug. 

PMID- 24297173
TI  - Connexin43 reduces melanoma growth within a keratinocyte microenvironment and
      during tumorigenesis in vivo.
AB  - Connexins (Cx) have been identified as tumor suppressors or enhancers, a
      distinction that appears to be dependent on the type and stage of disease.
      However, the role of connexins in melanoma tumorigenesis and their status during
      cancer onset and progression remain controversial and unclear. Here, we show that
      the aggressive B16-BL6 mouse melanoma cell line expresses low basal levels of
      Cx26 and Cx43, rendering them gap junctional intercellular communication
      deficient as elucidated by immunofluorescence, Western blotting, and dye transfer
      studies. Following ectopic expression of green fluorescent protein-tagged Cx26
      and Cx43 in these connexin-deficient melanomas, punctate gap junction-like
      plaques were evident at sites of cell-cell apposition, and the incidence of dye
      transfer was significantly increased similar to connexin-rich keratinocytes. We
      found that the expression of Cx43, but not Cx26, significantly reduced cellular
      proliferation and anchorage-independent growth from control melanomas, whereas
      migration was unaffected. Additionally, melanomas expressing Cx43 displayed
      significantly reduced growth within the in situ-like microenvironment of
      keratinocytes, despite a lack of heterocellular gap junctional intercellular
      communication between the two cell types. Furthermore, when grown in vivo in the
      chicken chorioallantoic membrane, primary tumors derived from Cx43-expressing
      melanomas were significantly smaller than controls, whereas Cx26-expressing
      melanomas produced tumors similar to controls. Collectively, these results
      suggest that Cx43, and not Cx26, can act as a tumor suppressor during melanoma
      tumorigenesis. 

PMID- 24297174
TI  - Mitochondria contribute to NADPH generation in mouse rod photoreceptors.
AB  - NADPH is the primary source of reducing equivalents in the cytosol. Its major
      source is considered to be the pentose phosphate pathway, but cytosolic NADP(+)
      dependent dehydrogenases using intermediates of mitochondrial pathways for
      substrates have been known to contribute. Photoreceptors, a nonproliferating cell
      type, provide a unique model for measuring the functional utilization of NADPH at
      the single cell level. In these cells, NADPH availability can be monitored from
      the reduction of the all-trans-retinal generated by light to all-trans-retinol
      using single cell fluorescence imaging. We have used mouse rod photoreceptors to
      investigate the generation of NADPH by different metabolic pathways. In the
      absence of extracellular metabolic substrates, NADPH generation was severely
      compromised. Extracellular glutamine supported NADPH generation to levels
      comparable to those of glucose, but pyruvate and lactate were relatively
      ineffective. At low extracellular substrate concentrations, partial inhibition of
      ATP synthesis lowered, whereas suppression of ATP consumption augmented NADPH
      availability. Blocking pyruvate transport into mitochondria decreased NADPH
      availability, and addition of glutamine restored it. Our findings demonstrate
      that in a nonproliferating cell type, mitochondria-linked pathways can generate
      substantial amounts of NADPH and do so even when the pentose phosphate pathway is
      operational. Competing demands for ATP and NADPH at low metabolic substrate
      concentrations indicate a vulnerability to nutrient shortages. By supporting
      substantial NADPH generation, mitochondria provide alternative metabolic pathways
      that may support cell function and maintain viability under transient nutrient
      shortages. Such pathways may play an important role in protecting against retinal
      degeneration. 

PMID- 24297175
TI  - Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of
      vascular Kv7 channels.
AB  - The Kv7 family (Kv7.1-7.5) of voltage-activated potassium channels contributes to
      the maintenance of resting membrane potential in excitable cells. Previously, we
      provided pharmacological and electrophysiological evidence that Kv7.4 and Kv7.5
      form predominantly heteromeric channels and that Kv7 activity is regulated by
      protein kinase C (PKC) in response to vasoconstrictors in vascular smooth muscle
      cells. Direct evidence for Kv7.4/7.5 heteromer formation, however, is lacking.
      Furthermore, it remains to be determined whether both subunits are regulated by
      PKC. Utilizing proximity ligation assays to visualize single molecule
      interactions, we now show that Kv7.4/Kv.7.5 heteromers are endogenously expressed
      in vascular smooth muscle cells. Introduction of dominant-negative Kv7.4 and
      Kv7.5 subunits in mesenteric artery myocytes reduced endogenous Kv7 currents by
      84 and 76%, respectively. Expression of an inducible protein kinase Calpha
      (PKCalpha) translocation system revealed that PKCalpha activation is sufficient
      to suppress endogenous Kv7 currents in A7r5 rat aortic and mesenteric artery
      smooth muscle cells. Arginine vasopressin (100 and 500 pm) and the PKC activator
      phorbol 12-myristate 13-acetate (1 nm) each inhibited human (h) Kv7.5 and
      hKv7.4/7.5, but not hKv7.4 channels expressed in A7r5 cells. A decrease in hKv7.5
      and hKv7.4/7.5 current densities was associated with an increase in PKC-dependent
      phosphorylation of the channel proteins. These findings provide further evidence
      for a differential regulation of Kv7.4 and Kv7.5 channel subunits by PKC
      dependent phosphorylation and new mechanistic insights into the role of
      heteromeric subunit assembly for regulation of vascular Kv7 channels. 

PMID- 24297176
TI  - Growth arrest by the antitumor steroidal lactone withaferin A in human breast
      cancer cells is associated with down-regulation and covalent binding at cysteine
      303 of beta-tubulin.
AB  - Withaferin A (WA), a C5,C6-epoxy steroidal lactone derived from a medicinal plant
      (Withania somnifera), inhibits growth of human breast cancer cells in vitro and
      in vivo and prevents mammary cancer development in a transgenic mouse model.
      However, the mechanisms underlying the anticancer effect of WA are not fully
      understood. Herein, we report that tubulin is a novel target of WA-mediated
      growth arrest in human breast cancer cells. The G2 and mitotic arrest resulting
      from WA exposure in MCF-7, SUM159, and SK-BR-3 cells was associated with a marked
      decrease in protein levels of beta-tubulin. These effects were not observed with
      the naturally occurring C6,C7-epoxy analogs of WA (withanone and withanolide A).
      A non-tumorigenic normal mammary epithelial cell line (MCF-10A) was markedly more
      resistant to mitotic arrest by WA compared with breast cancer cells. Vehicle
      treated control cells exhibited a normal bipolar spindle with chromosomes aligned
      along the metaphase plate. In contrast, WA treatment led to a severe disruption
      of normal spindle morphology. NMR analyses revealed that the A-ring enone in WA,
      but not in withanone or withanolide A, was highly reactive with cysteamine and
      rapidly succumbed to irreversible nucleophilic addition. Mass spectrometry
      demonstrated direct covalent binding of WA to Cys(303) of beta-tubulin in MCF-7
      cells. Molecular docking indicated that the WA-binding pocket is located on the
      surface of beta-tubulin and characterized by a hydrophobic floor, a hydrophobic
      wall, and a charge-balanced hydrophilic entrance. These results provide novel
      insights into the mechanism of growth arrest by WA in breast cancer cells. 

PMID- 24297177
TI  - Mutations in subunit interface and B-cell epitopes improve antileukemic
      activities of Escherichia coli asparaginase-II: evaluation of immunogenicity in
      mice.
AB  - L-Asparaginase-II from Escherichia coli (EcA) is a central component in the
      treatment of acute lymphoblastic leukemia (ALL). However, the therapeutic
      efficacy of EcA is limited due to immunogenicity and a short half-life in the
      patient. Here, we performed rational mutagenesis to obtain EcA variants with a
      potential to improve ALL treatment. Several variants, especially W66Y and Y176F,
      killed the ALL cells more efficiently than did wild-type EcA (WT-EcA), although
      nonleukemic peripheral blood monocytes were not affected. Several assays,
      including Western blotting, annexin-V/propidium iodide binding, comet, and
      micronuclei assays, showed that the reduction in viability of leukemic cells is
      due to the increase in caspase-3, cytochrome c release, poly(ADP-ribose)
      polymerase activation, down-regulation of anti-apoptotic protein Bcl-XL, an
      arrest of the cell cycle at the G0/G1 phase, and eventually apoptosis. Both W66Y
      and Y176F induced significantly more apoptosis in lymphocytes derived from ALL
      patients. In addition, Y176F and Y176S exhibited greatly decreased glutaminase
      activity, whereas K288S/Y176F, a variant mutated in one of the immunodominant
      epitopes, showed reduced antigenicity. Further in vivo immunogenicity studies in
      mice showed that K288S/Y176F was 10-fold less immunogenic as compared with WT
      EcA. Moreover, sera obtained from WT-EcA immunized mice and ALL patients who were
      given asparaginase therapy for several weeks recognized the K288S/Y176F mutant
      significantly less than the WT-EcA. Further mechanistic studies revealed that
      W66Y, Y176F, and K288S/Y176F rapidly depleted asparagine and also down-regulated
      the transcription of asparagine synthetase as compared with WT-EcA. These highly
      desirable attributes of these variants could significantly advance asparaginase
      therapy of leukemia in the future.

PMID- 24297178
TI  - Characterization of a stem-like subpopulation in basal-like ductal carcinoma in
      situ (DCIS) lesions.
AB  - Previously, we found that basal-like ductal carcinoma in situ (DCIS) contains
      cancer stem-like cells. Here, we characterize stem-like subpopulations in a model
      of basal-like DCIS and identify subpopulations of CD49f+/CD24- stem-like cells
      that possess aldehyde dehydrogenase 1 activity. We found that these cells show
      enhanced migration potential compared with non-stem DCIS cells. We also found
      that the chemopreventive agent sulforaphane can target these DCIS stem-like
      cells, reduce aldehyde dehydrogenase 1 (ALDH1) expression, and decrease
      mammosphere and progenitor colony formation. Furthermore, we characterized
      exosomal trafficking of microRNAs in DCIS and found that several microRNAs (miRs)
      including miR-140, miR-29a, and miR-21 are differentially expressed in exosomes
      from DCIS stem-like cells. We found that SFN treatment could reprogram DCIS stem
      like cells as evidenced by significant changes in exosomal secretion more closely
      resembling that of non-stem cancer cells. Finally, we demonstrated that exosomal
      secretion of miR-140 might impact signaling in nearby breast cancer cells. 

PMID- 24297179
TI  - cAMP responsive element modulator (CREM) alpha mediates chromatin remodeling of
      CD8 during the generation of CD3+ CD4- CD8- T cells.
AB  - TCR-alphabeta(+)CD3(+)CD4(-)CD8(-) "double negative" T cells are expanded in the
      peripheral blood of patients with systemic lupus erythematosus (SLE) and lupus
      prone mice. Double negative T cells have been claimed to derive from CD8(+) cells
      that down-regulate CD8 co-receptors and acquire a distinct effector phenotype
      that includes the expression of proinflammatory cytokines. This, along with the
      fact that double negative T cells have been documented in inflamed organs,
      suggests that they may contribute to disease expression and tissue damage. We
      recently linked the transcription factor cAMP responsive element modulator (CREM)
      alpha, which is expressed at increased levels in T cells from SLE patients and
      lupus prone MRL/lpr mice, with trans-repression of a region syntenic to the
      murine CD8b promoter. However, the exact molecular mechanisms that result in a
      stable silencing of both CD8A and CD8B genes remain elusive. Here, we demonstrate
      that CREMalpha orchestrates epigenetic remodeling of the CD8 cluster through the
      recruitment of DNA methyltransferase (DNMT) 3a and histone methyltransferase G9a.
      Thus, we propose that CREMalpha is essential for the expansion of double negative
      T cells in SLE. CREMalpha blockade may have therapeutic value in autoimmune
      disorders with DN T cell expansion. 

PMID- 24297180
TI  - Serine hydrolase inhibitors block necrotic cell death by preventing calcium
      overload of the mitochondria and permeability transition pore formation.
AB  - Perturbation of calcium signaling that occurs during cell injury and disease,
      promotes cell death. In mouse lung fibroblasts A23187 triggered mitochondrial
      permeability transition pore (MPTP) formation, lactate dehydrogenase (LDH)
      release, and necrotic cell death that were blocked by cyclosporin A (CsA) and
      EGTA. LDH release temporally correlated with arachidonic acid release but did not
      involve cytosolic phospholipase A2alpha (cPLA2alpha) or calcium-independent PLA2.
      Surprisingly, release of arachidonic acid and LDH from cPLA2alpha-deficient
      fibroblasts was inhibited by the cPLA2alpha inhibitor pyrrophenone, and another
      serine hydrolase inhibitor KT195, by preventing mitochondrial calcium uptake.
      Inhibitors of calcium/calmodulin-dependent protein kinase II, a mitochondrial
      Ca(2+) uniporter (MCU) regulator, also prevented MPTP formation and arachidonic
      acid release induced by A23187 and H2O2. Pyrrophenone blocked MCU-mediated
      mitochondrial calcium uptake in permeabilized fibroblasts but not in isolated
      mitochondria. Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn
      glycerol and CsA blocked cell death and arachidonic acid release not by
      preventing mitochondrial calcium uptake but by inhibiting MPTP formation. In
      fibroblasts stimulated with thapsigargin, which induces MPTP formation by a
      direct effect on mitochondria, LDH and arachidonic acid release were blocked by
      CsA and 1-oleoyl-2-acetyl-sn-glycerol but not by pyrrophenone or EGTA. Therefore
      serine hydrolase inhibitors prevent necrotic cell death by blocking mitochondrial
      calcium uptake but not the enzyme releasing fatty acids that occurs by a novel
      pathway during MPTP formation. This work reveals the potential for development of
      small molecule cell-permeable serine hydrolase inhibitors that block MCU-mediated
      mitochondrial calcium overload, MPTP formation, and necrotic cell death. 

PMID- 24297181
TI  - Molecular and thermodynamic mechanisms of the chloride-dependent human
      angiotensin-I-converting enzyme (ACE).
AB  - Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure
      and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I,
      bradykinin, and a number of other physiologically relevant peptides. sACE
      consists of two homologous and catalytically active N- and C-domains, which
      display marked differences in substrate specificities and chloride activation. A
      series of single substitution mutants were generated and evaluated under varying
      chloride concentrations using isothermal titration calorimetry. The x-ray crystal
      structures of the mutants provided details on the chloride-dependent interactions
      with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to
      affect positioning of residues from the active site. Analysis of the chloride 2
      pocket R522Q and R522K mutations revealed the key interactions with the catalytic
      site that are stabilized via chloride coordination of Arg(522). Substrate
      interactions in the S2 subsite were shown to affect chloride affinity in the
      chloride 2 pocket. The Glu(403)-Lys(118) salt bridge in C-domain ACE was shown to
      stabilize the hinge-bending region and reduce chloride affinity by constraining
      the chloride 2 pocket. This work demonstrated that substrate composition to the C
      terminal side of the scissile bond as well as interactions of larger substrates
      in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE
      C-domain, providing a rationale for the substrate-selective nature of chloride
      dependence in ACE and how this varies between the N- and C-domains. 

PMID- 24297182
TI  - The small GTPase Arf6 is essential for the Tram/Trif pathway in TLR4 signaling.
AB  - Recognition of lipopolysaccharides (LPS) by Toll-like receptor 4 (TLR4) at the
      plasma membrane triggers NF-kappaB activation through recruitment of the adaptor
      proteins Mal and MyD88. Endocytosis of the activated TLR4 allows recruitment of
      the adaptors Tram and Trif, leading to activation of the transcription factor
      IRF3 and interferon production. The small GTPase ADP-ribosylation factor 6 (Arf6)
      was shown to regulate the plasma membrane association of Mal. Here we demonstrate
      that inhibition of Arf6 also markedly reduced LPS-induced cytokine production in
      Mal(-/-) mouse macrophages. In this article, we focus on a novel role for Arf6 in
      the MyD88-independent TLR4 pathway. MyD88-independent IRF3 activation and IRF3
      dependent gene transcription were strictly dependent on Arf6. Arf6 was involved
      in transport of Tram to the endocytic recycling compartment and internalization
      of LPS, possibly explaining its requirement for LPS-induced IRF3 activation.
      Together, these results show a critical role for Arf6 in regulating Tram/Trif
      dependent TLR4 signaling. 

PMID- 24297184
TI  - A novel "oxygen-induced" greening process in a cyanobacterial mutant lacking the
      transcriptional activator ChlR involved in low-oxygen adaptation of tetrapyrrole
      biosynthesis.
AB  - ChlR activates the transcription of the chlAII-ho2-hemN operon in response to low
      oxygen conditions in the cyanobacterium Synechocystis sp. PCC 6803. Three genes
      in the operon encode low-oxygen-type enzymes to bypass three oxygen-dependent
      reactions in tetrapyrrole biosynthesis. A chlR-lacking mutant, DeltachlR, shows
      poor photoautotrophic growth due to low chlorophyll (Chl) content under low
      oxygen conditions, which is caused by no induction of the operon. Here, we
      characterized the processes of etiolation of DeltachlR cells in low-oxygen
      conditions and the subsequent regreening of the etiolated cells upon exposure to
      oxygen, by HPLC, Western blotting, and low-temperature fluorescence spectra. The
      Chl content of the etiolated DeltachlR cells incubated under low-oxygen
      conditions for 7 days was only 10% of that of the wild-type with accumulation of
      almost all intermediates of the magnesium branch of Chl biosynthesis. Both
      photosystem I (PSI) and photosystem II (PSII) were significantly decreased,
      accompanied by a preferential decrease of antenna Chl in PSI. Upon exposure to
      oxygen, the etiolated DeltachlR cells resumed to produce Chl after a short lag
      (~2 h), and the level at 72 h was 80% of that of the wild-type. During this novel
      "oxygen-induced" greening process, the PSI and PSII contents were largely
      increased in parallel with the increase in Chl contents. After 72 h, the PSI
      content reached ~50% of the wild-type level in contrast to the full recovery of
      PSII. DeltachlR provides a promising alternative system to investigate the
      biogenesis of PSI and PSII. 

PMID- 24297183
TI  - Androgen receptor splice variant AR3 promotes prostate cancer via modulating
      expression of autocrine/paracrine factors.
AB  - Deregulation of androgen receptor (AR) splice variants has been implicated to
      play a role in prostate cancer development and progression. To understand their
      functions in prostate, we established a transgenic mouse model (AR3Tg) with
      targeted expression of the constitutively active and androgen-independent AR
      splice variant AR3 (a.k.a. AR-V7) in prostate epithelium. We found that
      overexpression of AR3 modulates expression of a number of tumor-promoting
      autocrine/paracrine growth factors (including Tgfbeta2 and Igf1) and expands
      prostatic progenitor cell population, leading to development of prostatic
      intraepithelial neoplasia. In addition, we showed that some epithelial
      mesenchymal transition-associated genes are up-regulated in AR3Tg prostates,
      suggesting that AR3 may antagonize AR activity and halt the differentiation
      process driven by AR and androgen. This notion is supported by our observations
      that the number of Ck5(+)/Ck8(+) intermediate cells is increased in AR3Tg
      prostates after castration, and expression of AR3 transgene in these intermediate
      cells compromises prostate epithelium regeneration upon androgen replacement. Our
      results demonstrate that AR3 is a driver of prostate cancer, at least in part,
      through modulating multiple tumor-promoting autocrine/paracrine factors. 

PMID- 24297185
TI  - L-lactate production from seaweed hydrolysate of Laminaria japonica using
      metabolically engineered Escherichia coli.
AB  - Renewable and carbon neutral, marine algal biomass could be an attractive
      alternative substrate for the production of biofuel and various biorefinery
      products. Thus, the feasibility of brown seaweed (Laminaria japonica) hydrolysate
      as a carbon source was investigated here for L-lactate production. This work
      reports the homofermentative route for L-lactate production by introducing
      Streptococcus bovis/equinus L-lactate dehydrogenase in an engineered Escherichia
      coli strain where synthesis of the competing by-product was blocked. The
      engineered strain utilized both glucose and mannitol present in the hydrolysate
      under microaerobic condition and produced 37.7 g/L of high optical purity L
      lactate at 80 % of the maximum theoretical value. The result shown in this study
      implies that algal biomass would be as competitive with lignocellulosic biomass
      in terms of lactic acid production and that brown seaweed can be used as a
      feedstock for the industrial production of other chemicals.

PMID- 24297186
TI  - Adiponectin signaling in the liver.
AB  - High glucose production contributes to fed and fasted hyperglycemia in Type 1
      Diabetes (T1D) and Type 2 Diabetes (T2D). The breakdown of the adiponectin
      signaling pathway in T1D and the reduction of circulating adiponectin in T2D
      contribute to this abnormal increase in glucose production. Sufficient amounts of
      insulin could compensate for the loss of adiponectin signaling in T1D and T2D and
      reduce hyperglycemia. However, the combination of low adiponectin signaling and
      high insulin resembles an insulin resistance state associated with cardiovascular
      disease, fatty liver disease and decreased life expectancy. The future
      development of "adiponectin sensitizers", medications that correct the deficiency
      in adiponectin signaling, could restore the metabolic balance in T1D and T2D and
      reduce the need for insulin. This article reviews the adiponectin signaling
      pathway in the liver through T-cadherin, AdipoR1, AdipoR2, AMPK, ceramidase
      activity, APPL1 and the recently discovered Suppressor Of Glucose from Autophagy
      (SOGA). 

PMID- 24297187
TI  - Primary CNS lymphoma treated with radiotherapy in Japan: a survey of patients
      treated in 2005-2009 and a comparison with those treated in 1985-2004.
AB  - BACKGROUND: The aim of our study was to analyze changes over time in the
      characteristics, treatment, and outcome of patients with primary central nervous
      system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven
      PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20
      Japanese institutions using a questionnaire. These data were then compared with
      data on 273 patients treated during the period 1995-2004 and those on 466
      patients treated during the period 1985-1994. RESULTS: In terms of patient and
      tumor characteristics, we found a significant increase in mean patient age in the
      2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years,
      respectively) and in the percentage of patients with better performance status
      (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health
      Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to
      the 1995-2004 period, significant changes in the 2005-2009 period were (1)
      decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of
      chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)
      containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3,
      30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009
      periods, respectively, but relapse-free survival did not improve between the 1995
      2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients
      receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44
      % during these three periods, respectively. CONCLUSIONS: Although patient
      backgrounds differed among the study periods, recent trends were a high patient
      age, better PS, avoidance of extensive tumor resection, more frequent use of
      chemotherapy, and improved survival. The recent improvement in survival may be
      due to improvements in second-line treatment and supportive care.

PMID- 24297188
TI  - Atrial ectopy as a predictor of incident atrial fibrillation: a cohort study.
AB  - BACKGROUND: Atrial fibrillation (AF) prediction models have unclear clinical
      utility given the absence of AF prevention therapies and the immutability of many
      risk factors. Premature atrial contractions (PACs) play a critical role in AF
      pathogenesis and may be modifiable. OBJECTIVE: To investigate whether PAC count
      improves model performance for AF risk. DESIGN: Prospective cohort study.
      SETTING: 4 U.S. communities. PATIENTS: A random subset of 1260 adults without
      prevalent AF enrolled in the Cardiovascular Health Study between 1989 and 1990.
      MEASUREMENTS: The PAC count was quantified by 24-hour electrocardiography.
      Participants were followed for the diagnosis of incident AF or death. The
      Framingham AF risk algorithm was used as the comparator prediction model.
      RESULTS: In adjusted analyses, doubling the hourly PAC count was associated with
      a significant increase in AF risk (hazard ratio, 1.17 [95% CI, 1.13 to 1.22]; P <
      0.001) and overall mortality (hazard ratio, 1.06 [CI, 1.03 to 1.09]; P < 0.001).
      Compared with the Framingham model, PAC count alone resulted in similar AF risk
      discrimination at 5 and 10 years of follow-up and superior risk discrimination at
      15 years. The addition of PAC count to the Framingham model resulted in
      significant 10-year AF risk discrimination improvement (c-statistic, 0.65 vs.
      0.72; P < 0.001), net reclassification improvement (23.2% [CI, 12.8% to 33.6%]; P
      < 0.001), and integrated discrimination improvement (5.6% [CI, 4.2% to 7.0%]; P <
      0.001). The specificity for predicting AF at 15 years exceeded 90% for PAC counts
      more than 32 beats/h. LIMITATION: This study does not establish a causal link
      between PACs and AF. CONCLUSION: The addition of PAC count to a validated AF risk
      algorithm provides superior AF risk discrimination and significantly improves
      risk reclassification. Further study is needed to determine whether PAC
      modification can prospectively reduce AF risk. PRIMARY FUNDING SOURCE: American
      Heart Association, Joseph Drown Foundation, and National Institutes of Health.

PMID- 24297189
TI  - Pegylated interferon-alpha2a with or without low-dose ribavirin for treatment
      naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a
      randomized trial.
AB  - BACKGROUND: Data are limited on the efficacy and safety of pegylated interferon
      plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving
      hemodialysis. OBJECTIVE: To compare the efficacy and safety of combination
      therapy with pegylated interferon plus low-dose ribavirin and pegylated
      interferon monotherapy for treatment-naive patients with HCV-1 receiving
      hemodialysis. DESIGN: Open-label, randomized, controlled trial.
      (ClinicalTrials.gov: NCT00491244). SETTING: 8 centers in Taiwan. PATIENTS: 205
      treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION: 48
      weeks of pegylated interferon-alpha2a, 135 ug weekly, plus ribavirin, 200 mg
      daily (n = 103), or pegylated interferon-alpha2a, 135 ug weekly (n = 102).
      MEASUREMENTS: Sustained virologic response rate and adverse event-related
      withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a
      greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95%
      CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had
      hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs.
      6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving
      combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449]
      vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks
      [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-beta than patients receiving
      monotherapy. The adverse event-related withdrawal rates were 7% in the
      combination therapy group and 4% in the monotherapy group (risk difference, 3%
      [CI, -3% to 9%]). LIMITATION: Open-label trial; results may not be generalizable
      to patients on peritoneal dialysis. CONCLUSION: In treatment-naive patients with
      HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus
      low-dose ribavirin achieved a greater sustained virologic response rate than
      pegylated interferon monotherapy. PRIMARY FUNDING SOURCE: National Center of
      Excellence for Clinical Trial and Research.

PMID- 24297190
TI  - Examination of links between herpes zoster incidence and childhood varicella
      vaccination.
AB  - BACKGROUND: Introduction of a universal varicella vaccine program for U.S.
      children in 1996 sparked concern that less-frequent exposure to varicella would
      decrease external boosting of immunity to varicella zoster virus and thereby
      increase incidence of herpes zoster (HZ). OBJECTIVE: To determine whether the
      varicella vaccination program has influenced trends in HZ incidence in the U.S.
      population older than 65 years. DESIGN: Retrospective study of Medicare claims.
      SETTING: Medicare, 1992 through 2010. PARTICIPANTS: 2 848 765 beneficiaries older
      than 65 years. MEASUREMENTS: Annual HZ incidence from 1992 through 2010; rate
      ratios (RRs) for HZ incidence by age, sex, and race or ethnicity; and state-level
      varicella vaccination coverage. RESULTS: 281 317 incident cases of HZ occurred.
      Age- and sex-standardized HZ incidence increased 39% from 10.0 per 1000 person
      years in 1992 to 13.9 per 1000 person-years in 2010 with no evidence of a
      statistically significant change in the rate of increase after introduction of
      the varicella vaccination program. Before introduction of this program, HZ
      incidence was higher in women (RR, 1.21 [95% CI, 1.19 to 1.24]) than men and was
      lower in black persons (RR, 0.51 [CI, 0.48 to 0.53]) and Hispanic persons (RR,
      0.76 [CI, 0.72 to 0.81]) than white persons. In a model adjusted for sex, age,
      and calendar year from 1997 to 2010, HZ incidence did not vary by state varicella
      vaccination coverage (RR, 0.9998 [CI, 0.9993 to 1.0003]). LIMITATION: Uncertain
      level and consistency of health-seeking behavior and access and uncertain
      accuracy of disease coding. CONCLUSION: Age-specific HZ incidence increased in
      the U.S. population older than 65 years even before implementation of the
      childhood varicella vaccination program. Introduction and widespread use of the
      vaccine did not seem to affect this increase. This information is reassuring for
      countries considering universal varicella vaccination. PRIMARY FUNDING SOURCE:
      None.

PMID- 24297191
TI  - Treatment of anemia in patients with heart disease: a systematic review.
AB  - BACKGROUND: The benefits of anemia treatment in patients with heart disease are
      uncertain. PURPOSE: To evaluate the benefits and harms of treatments for anemia
      in adults with heart disease. DATA SOURCES: MEDLINE, EMBASE, and Cochrane
      databases; clinical trial registries; reference lists; and technical advisors.
      STUDY SELECTION: English-language trials of blood transfusions, iron, or
      erythropoiesis-stimulating agents in adults with anemia and congestive heart
      failure or coronary heart disease and observational studies of transfusion. DATA
      EXTRACTION: Data on study design, population characteristics, hemoglobin levels,
      and health outcomes were extracted. Trials were assessed for quality. DATA
      SYNTHESIS: Low-strength evidence from 6 trials and 26 observational studies
      suggests that liberal transfusion protocols do not improve short-term mortality
      rates compared with less aggressive protocols (combined relative risk among
      trials, 0.94 [95% CI, 0.61 to 1.42]; I2 = 16.8%), although decreased mortality
      rates occurred in a small trial of patients with the acute coronary syndrome
      (1.8% vs. 13.0%; P = 0.032). Moderate-strength evidence from 3 trials of
      intravenous iron found improved short-term exercise tolerance and quality of life
      in patients with heart failure. Moderate- to high-strength evidence from 17
      trials of erythropoiesis-stimulating agent therapy found they offered no
      consistent benefits, but their use may be associated with harms, such as venous
      thromboembolism. LIMITATIONS: Few trials have examined transfusions in patients
      with heart disease, and observational studies are potentially confounded by
      indication. Data supporting iron use come mainly from 1 large trial, and long
      term effects are unknown. CONCLUSION: Higher transfusion thresholds do not
      consistently improve mortality rates, but large trials are needed. Intravenous
      iron may help to alleviate symptoms in patients with heart failure and iron
      deficiency and also warrants further study. Erythropoiesis-stimulating agents do
      not seem to benefit patients with mild to moderate anemia and heart disease and
      may be associated with serious harms. PRIMARY FUNDING SOURCE: U.S. Department of
      Veterans Affairs.

PMID- 24297192
TI  - Are metabolically healthy overweight and obesity benign conditions?: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Recent interest has focused on a unique subgroup of overweight and
      obese individuals who have normal metabolic features despite increased adiposity.
      Normal-weight individuals with adverse metabolic status have also been described.
      However, it remains unclear whether metabolic phenotype modifies the morbidity
      and mortality associated with higher body mass index (BMI). PURPOSE: To determine
      the effect of metabolic status on all-cause mortality and cardiovascular events
      in normal-weight, overweight, and obese persons. DATA SOURCES: Studies were
      identified from electronic databases. STUDY SELECTION: Included studies evaluated
      all-cause mortality or cardiovascular events (or both) and clinical
      characteristics of 6 patient groups defined by BMI category (normal
      weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined
      by the presence or absence of components of the metabolic syndrome by Adult
      Treatment Panel III or International Diabetes Federation criteria. DATA
      EXTRACTION: Two independent reviewers extracted the data. Metabolically healthy
      people of normal weight made up the reference group. DATA SYNTHESIS: Eight
      studies (n = 61 386; 3988 events) evaluated participants for all-cause mortality
      and/or cardiovascular events. Metabolically healthy obese individuals (relative
      risk [RR], 1.24; 95% CI, 1.02 to 1.55) had increased risk for events compared
      with metabolically healthy normal-weight individuals when only studies with 10 or
      more years of follow-up were considered. All metabolically unhealthy groups had a
      similarly elevated risk: normal weight (RR, 3.14; CI, 2.36 to 3.93), overweight
      (RR, 2.70; CI, 2.08 to 3.30), and obese (RR, 2.65; CI, 2.18 to 3.12). LIMITATION:
      Duration of exposure to the metabolic-BMI phenotypes was not described in the
      studies and could partially affect the estimates. CONCLUSION: Compared with
      metabolically healthy normal-weight individuals, obese persons are at increased
      risk for adverse long-term outcomes even in the absence of metabolic
      abnormalities, suggesting that there is no healthy pattern of increased weight.
      PRIMARY FUNDING SOURCE: Intramural funds from the Leadership Sinai Centre for
      Diabetes.

PMID- 24297193
TI  - Treatment of anemia in patients with heart disease: a clinical practice guideline
      from the American College of Physicians.
AB  - DESCRIPTION: The American College of Physicians (ACP) developed this guideline to
      present the evidence and provide clinical recommendations on the treatment of
      anemia and iron deficiency in adult patients with heart disease. METHODS: This
      guideline is based on published literature in the English language on anemia and
      iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the
      Cochrane Library. Literature was reassessed in April 2013, and additional studies
      were included. Outcomes evaluated for this guideline included mortality;
      hospitalization; exercise tolerance; quality of life; and cardiovascular events
      (defined as myocardial infarction, congestive heart failure exacerbation,
      arrhythmia, or cardiac death) and harms, including hypertension, venous
      thromboembolic events, and ischemic cerebrovascular events. The target audience
      for this guideline includes all clinicians, and the target patient population is
      anemic or iron-deficient adult patients with heart disease. This guideline grades
      the evidence and recommendations using the ACP's clinical practice guidelines
      grading system. RECOMMENDATION 1: ACP recommends using a restrictive red blood
      cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared
      with higher hemoglobin levels) in hospitalized patients with coronary heart
      disease. (Grade: weak recommendation; low-quality evidence) RECOMMENDATION 2: ACP
      recommends against the use of erythropoiesis-stimulating agents in patients with
      mild to moderate anemia and congestive heart failure or coronary heart disease.
      (Grade: strong recommendation; moderate-quality evidence).

PMID- 24297195
TI  - Still learning from SARS.

PMID- 24297196
TI  - Texting while doctoring: a patient safety hazard.

PMID- 24297197
TI  - Ectopy and expectations: can we predict atrial fibrillation, and should we try?

PMID- 24297199
TI  - The myth of healthy obesity.

PMID- 24297200
TI  - Death of a blow-up doll.

PMID- 24297201
TI  - The mark of a cane.

PMID- 24297202
TI  - Acute gastrointestinal bleeding.

PMID- 24297203
TI  - Acute gastrointestinal bleeding.

PMID- 24297204
TI  - The 2013 lung allocation controversy.

PMID- 24297205
TI  - The 2013 lung allocation controversy.

PMID- 24297206
TI  - Carbon monoxide from domestic coffee roasting: a case report.

PMID- 24297207
TI  - Summaries for patients. Pegylated interferon with or without ribavirin for
      patients with hepatitis C receiving hemodialysis.

PMID- 24297208
TI  - Summaries for patients. Is obesity harmful if metabolic factors are normal?

PMID- 24297209
TI  - Summaries for patients. Treatment of anemia in patients with heart disease: A
      clinical practice guideline from the American College of Physicians.

PMID- 24297210
TI  - In the clinic. Generalized anxiety disorder.

PMID- 24297211
TI  - Novel chiral (salen)Mn(III) complexes containing a calix[4]arene unit in 1,3
      alternate conformation as catalysts for enantioselective epoxidation reactions of
      (Z)-aryl alkenes.
AB  - Two new chiral calix[4]arene-salen ligands 1a,b, based on calix[4]arene platforms
      in 1,3-alternate conformation, have been prepared by a new general synthetic
      pathway. Their Mn(III) complexes, 3a,b have shown fairly good efficiency in the
      asymmetric epoxidation of styrene and substituted styrenes, whereas excellent
      catalytic activity and selectivity were observed with rigid bicyclic alkenes,
      namely 1,2-dihydro-naphthalene and substituted 2,2'-dimethyl-chromene. The higher
      catalytic properties of 3a may be ascribed to the more rigid and inherently
      chiral structure as proved by molecular modelling, NMR spectroscopy and X-ray
      data of the similarly structured UO2 complexes 2a,b.

PMID- 24297212
TI  - Bromo- and thiomaleimides as a new class of thiol-mediated fluorescence 'turn-on'
      reagents.
AB  - Bromo- and thiomaleimides are shown to serve as highly effective quenchers of a
      covalently attached fluorophore. Reactions with thiols that lead to removal of
      the maleimide conjugation, or detachment of the fluorophore from the maleimide,
      result in 'turn-on' of the fluorescence. These reagents thus offer opportunities
      in thiol sensing and intracellular reporting. 

PMID- 24297213
TI  - Effect of preoperative limb-length discrepancy on abductor strength after total
      hip arthroplasty in patients with developmental dysplasia of the hip.
AB  - BACKGROUND: Limb-length discrepancy (LLD) arising from hip subluxation or
      dislocation and accompanied by insufficiency of hip abductor in patients with
      developmental dysplasia of the hip (DDH) can be corrected partially or completely
      with total hip arthroplasty (THA). However, information about post-THA changes in
      abductor strength related to preoperative LLD in patients with DDH is lacking. We
      aimed to explore the post-THA recovery course of abductor muscle strength and its
      related factors in patients with DDH. METHODS: A cohort of 45 patients with
      unilateral DDH was divided into two groups according to their Crowe
      classification: patients with class I or II DDH formed Group M, and patients in
      class III and IV DDH formed Group S. The following parameters were measured on
      standardized antero-posterior hip radiographs taken in the supine position pre-
      and post-THA: abductor muscle length, abductor lever arm, LLD, and femoral offset
      (FO). Abductor strength was evaluated quantitatively with the Isomed 2000
      isokinetic test system (1 week before the operation and 1, 3, 6, and 12 months
      after the operation). The contralateral normal hip joint served as a within
      patient control. The affected side:healthy side ratios of the parameters above
      were calculated. RESULTS: Abductor strength ratio evaluated at the five follow-up
      time points was larger in Group M than that in Group S (p < 0.001). The average
      abductor strength ratio reached 78.5, 85.4, and 89.2% at the 3, 6, and 12 months
      postoperative exams, respectively, in Group M, and reached 50.3, 63.2, and 72.9%
      in Group S. The abductor muscle length ratio, the abductor muscle level arm
      ratio, and the FO ratio were significantly increased postoperatively, relative to
      preoperative assessment, in the two groups. LLD was reduced significantly
      postoperatively, relative to preoperative values, in both groups. Both
      preoperative LLD (r = -0.791, p < 0.001) and the change in abductor muscle length
      ratio (r = -0.659, p < 0.001) correlated with abductor strength recovery.
      CONCLUSION: Patients showed the greatest improvement in abductor strength within
      the first 6 months after THA, especially during the first 3 months. Abductor
      strength was consistently greater in patients with mild dysplasia than in
      patients with severe dysplasia. The extent of preoperative LLD and the increase
      in abductor length were related with post-THA abductor strength recovery in
      patients with DDH.

PMID- 24297214
TI  - Orthogeriatric model for hip fracture patients in Singapore: our early experience
      and initial outcomes.
AB  - INTRODUCTION: The aging population is growing rapidly in Asia resulting in an
      increased number of fragility fractures. Studies have shown that an integrated
      model of care for the elderly can improve the quality of patient care and
      outcomes. This report describes our concept, initial experience and short-term
      outcomes of the integrated model of care that was established in managing
      geriatric hip fractures in Tan Tock Seng Hospital, Singapore. PATIENT AND
      METHODS: An integrated care pathway model was implemented. The principle of the
      model is based on (a) timely admission, review, surgery, rehabilitation,
      transfer, (b) multidisciplinary approach and (c) integration of a care manager.
      Hip fracture patients (>60 years) were included in our study and were followed up
      for 1 year. Demographic data, Charlson comorbidity index (CCI), time to surgery,
      length of stay and modified Barthel index (MBI) scores were recorded. RESULTS:
      The mean age was 82 years (62-108) with a female predominance (75 %). The mean
      CCI was 1.8. Time to admission was 3.7 h and mean time taken to be reviewed by an
      integrated care manager was 21.7 h. Close to 40 % of patients were operated
      within 48 h with a median time to surgery of 36.7 h. Mean length of stay was 10
      days with an inpatient and 1-year mortality rate of 2.3 and 5.9 %, respectively.
      Complication rate was 5.1 % (urinary tract infection and wound infection) and MBI
      scores at 1 year revealed significant functional improvement of 95 % (p < 0.01).
      CONCLUSION: Our integrated model of care for hip fractures can lead to
      satisfactory outcomes. Though the time to surgery and length of stay can be
      improved further, our initial results have shown a reasonable time to admission
      and review by a care manager. Besides a low complication and mortality rate,
      functional improvement was significant post-operatively.

PMID- 24297215
TI  - Long-term results of the augmented PFNA: a prospective multicenter trial.
AB  - BACKGROUND: Pertrochanteric fractures are increasing and their operative
      treatment remains under discussion. Failures needing reoperations such as a cut
      out are reported to be high and are associated with multiple factors including
      poor bone quality, poor fracture reduction and improper implant placement. The
      PFNA((r)) with perforated blade offers an option for standardized cement
      augmentation with a PMMA cement to provide more stability to the fracture
      fixation. It remains unclear if the augmentation of this implant does any harm in
      a longer time span. This prospective multicenter study shows clinical and
      radiological results with this implant with a mean follow-up time of 15 months.
      METHODS: In 5 European clinics, 62 patients (79 % female, mean age 85.3 years)
      suffering from an osteoporotic pertrochanteric fracture (AO 31) were treated with
      the augmented PFNA((r)). The primary objectives were assessment of activities of
      daily living, pain and mobility. Furthermore, the X-rays were analyzed for the
      cortical thickness index, changes of the trabecular structure around the cement
      and the hip joint space. RESULTS: The mean follow-up time was 15.3 months. We
      observed callus healing in all cases. The surgical complication rate was 3.2 %
      with no complication related to the cement augmentation. A mean volume of 3.8 ml
      of cement was injected and no complication was reported due to this procedure.
      59.9 % reached their prefracture mobility level until follow-up. The mean hip
      joint space did not change significantly until follow-up and there were no signs
      of osteonecrosis in the follow-up X-rays. Furthermore, no blade migration was
      assessed. CONCLUSION: This study makes us believe that the standardized
      augmentation of the PFNA with a perforated blade is a safe method to treat
      pertrochanteric femoral fractures. It leads to good functional results and is not
      associated with cartilage or bone necrosis.

PMID- 24297216
TI  - Oxidative stress and aging: correlation with clinical parameters.
AB  - BACKGROUND AND AIMS: The free radical theory of aging has been receiving a lot of
      attention in the past years. The aim of this study was to examine the correlation
      between oxidative damage, antioxidant enzyme activities and plasma antioxidant
      potential with clinical parameters in elderly people. METHODS: Elderly subjects
      over 80 years old were included in the study. Clinical data were collected based
      on the Cumulative Illness Rating Scale (n = 132). In addition, blood samples were
      collected to determine biochemical and oxidative stress. RESULTS: The results
      showed that the mean age of the participants was 85.1 +/- 4.0 years old. Diabetic
      patients presented higher plasma protein carbonyl levels when compared with non
      diabetic, and plasma levels of thiobarbituric acid-reactive substances were
      correlated to serum triglyceride and LDL fraction. In contrast, a lower plasma
      total antioxidant capacity presented a relation with the presence of diabetes and
      arterial hypertension. In addition, healthy elderly subjects presented a higher
      plasma total antioxidant capacity. CONCLUSION: Thus, it seemed that plasma
      antioxidant potential is a better predictor of successful aging in the elderly
      than oxidative damage parameters or plasma antioxidant enzyme activities.

PMID- 24297217
TI  - Indoor mobility-related fatigue and muscle strength in nonagenarians: a
      prospective longitudinal study.
AB  - BACKGROUND AND AIMS: Mobility-related fatigue is an important indicator of
      functional decline in old age, however, very little is known about fatigue in the
      oldest old population segment. The aim of this study was to examine the
      association between indoor mobility-related fatigue and muscle strength decline
      in nonagenarians. METHODS: The study is based on a prospective longitudinal study
      of all Danes born in 1905 and assessed in 1998, 2000 and 2003, and includes 92-
      to 93-year-old persons who were independent of help in basic indoor mobility at
      baseline (n = 1,353). Fatigue was assessed at baseline and defined as a
      subjective feeling of fatigue when transferring or walking indoors. The outcome
      measure, maximum grip strength, was measured at each measurement point. RESULTS:
      Grip strength declined throughout the study in participants with and without
      fatigue, but those reporting fatigue had significantly (P < .001) lower muscle
      strength during the entire study period. Longitudinal analyses indicated slightly
      slower decline in muscle strength among participants with fatigue compared to
      those without; however, observed selective dropout of participants with fatigue
      and poor performance at baseline needs to be considered when interpreting the
      results. Accordingly, participants without fatigue had significantly higher
      chances of being alive and having muscle strength above gender-specific median at
      first (RR 1.32, 95 % CI 1.07-1.58), second (RR 1.51, 1.06-1.96) and third (RR
      1.39, 1.01-1.97) measurement points. CONCLUSIONS: Indoor mobility-related fatigue
      in advanced later life should not merely be considered as an unpleasant symptom,
      but rather an indicator of physical impairment, and consequently declined
      physiological reserve.

PMID- 24297218
TI  - Introduction: revisiting the "negrito" hypothesis: a transdisciplinary approach
      to human prehistory in southeast Asia.
AB  - The "negrito" hypothesis predicts that a shared phenotype among various
      contemporary groups of hunter-gatherers in Southeast Asia--dark skin, short
      stature, tight curly hair--is due to common descent from a region-wide, pre
      Neolithic substrate of humanity. The alternative is that their distinctive
      phenotype results from convergent evolution. The core issues of the negrito
      hypothesis are today more relevant than ever to studies of human evolution,
      including the out-of-Africa migration, admixture with Denisovans, and the effects
      of environment and ecology on life-history traits. Understanding the current
      distribution of the negrito phenotype dictates a wide-ranging remit for study,
      including the articulation of the relationship between foragers and farmers in
      the present, the development of settled agriculture in the mid-Holocene, and
      terminal Pleistocene population expansions. The consensus reached by the
      contributors to this special double issue of Human Biology is that there is not
      yet conclusive evidence either for or against the negrito hypothesis.
      Nevertheless, the process of revisiting the problem will benefit the knowledge of
      the human prehistory of Southeast Asia. Whether the term negrito accurately
      reflects the all-encompassing nature of the resulting inquiry is in itself
      questionable, but the publication of this double issue is testament to the
      enduring ability of this hypothesis to unite disparate academic disciplines in a
      common purpose.

PMID- 24297219
TI  - Hunter-gatherers in southeast Asia: from prehistory to the present.
AB  - Anatomically modern hunter-gatherers expanded from Africa into Southeast Asia at
      least 50,000 years ago, where they probably encountered and interacted with
      populations of Homo erectus and Homo floresiensis and the recently discovered
      Denisovans. Simulation studies suggest that these hunter-gatherers may well have
      followed a coastal route that ultimately led to the settlement of Sahul, while
      archaeology confirms that they also crossed significant seas and explored well
      into the interior. They also adapted to marked environmental changes that
      alternated between relatively cool and dry conditions and warmer, wetter
      interludes. During the former, the sea fell by up to 120 m below its present
      level, which opened up a vast low-lying area known as Sundaland. Three principal
      alignments can be identified: the first involved the occupation of rock shelters
      in upland regions, the second has identified settlement on broad riverine
      floodplains, and the last concentrated on the raised beaches formed from about
      five millennia ago when the sea level was elevated above its present position.
      This cultural sequence was dislocated about 4 kya when rice and millet farmers
      infiltrated the lowlands of Southeast Asia ultimately from the Yangtze River
      valley. It is suggested that this led to two forms of interaction. In the first,
      the indigenous hunter-gatherers integrated with intrusive Neolithic communities
      and, while losing their cultural identity, contributed their genes to the present
      population of Southeast Asia. In the second, hunter-gatherers withdrew to
      rainforest refugia and, through selective pressures inherent in such an
      environment, survived as the small-bodied, dark-skinned humans found to this day
      in the Philippines, Peninsular Malaysia and Thailand, and the Andaman Islands.
      Beyond the impact of expansive rice farmers in Melanesia and Australia, hunter
      gatherers continued to dominate until they encountered European settlement. 

PMID- 24297220
TI  - "Small size" in the Philippine human fossil record: is it meaningful for a better
      understanding of the evolutionary history of the negritos?
AB  - "Pygmy populations" are recognized in several places over the world, especially
      in Western Africa and in Southeast Asia (Philippine "negritos," for instance).
      Broadly defined as "small-bodied Homo sapiens" (compared with neighboring
      populations), their origins and the nature of the processes involved in the
      maintenance of their phenotype over time are highly debated. Major results have
      been recently obtained from population genetics on present-day negrito
      populations, but their evolutionary history remains largely unresolved. We
      present and discuss the Upper Pleistocene human remains recovered from Tabon Cave
      and Callao Cave in the Philippines, which are potentially highly relevant to
      these research questions. Human fossils have been recovered in large numbers from
      Tabon Cave (Palawan Island) but mainly from reworked and mixed sediments from
      several archaeological layers. We review and synthesize the long and meticulous
      collaborative work done on the archives left from the 1960s excavations and on
      the field. The results demonstrate the long history of human occupations in the
      cave, since at least ~30,000 BP. The examination of the Tabon human remains shows
      a large variability: large and robust for one part of the sample, and small and
      gracile for the other part. The latter would fit quite comfortably within the
      range of variation of Philippine negritos. Farther north, on Luzon Island, the
      human third metatarsal recently recovered from Callao Cave and dated to ~66,000
      BP is now the oldest direct evidence of human presence in the Philippines.
      Previous data show that, compared with H. sapiens (including Philippine
      negritos), this bone presents a very small size and several unusual morphological
      characteristics. We present a new analytical approach using three-dimensional
      geometric morphometrics for comparing the Callao fossil to a wide array of extant
      Asian mammals, including nonhuman primates and H. sapiens. The results
      demonstrate that the shape of the Callao metatarsal is definitely closer to
      humans than to any other groups. The fossil clearly belongs to the genus Homo;
      however, it remains at the margin of the variation range of H. sapiens. Because
      of its great antiquity and the presence of another diminutive species of the
      genus Homo in the Wallace area during this time period (H. floresiensis), we
      discuss here in detail the affinities and potential relatedness of the Callao
      fossil with negritos that are found today on Luzon Island. 

PMID- 24297221
TI  - The skeletal phenotype of "negritos" from the Andaman Islands and Philippines
      relative to global variation among hunter-gatherers.
AB  - The "negrito hypothesis" suggests that populations of small-bodied foragers in
      South and Southeast Asia who share common phenotypic characteristics may also
      share a common, ancient origin. The key defining characteristics of the "negrito"
      phenotype, small body size, dark skin, and tightly curled hair, have been
      interpreted as linking these populations to sub-Saharan Africans. The underlying
      assumption of this interpretation is that the observed phenotypic similarities
      likely reflect shared ancestry rather than phenotypic convergence. Current
      genetic evidence is inconclusive, as it both demonstrates that negrito
      populations have genetic affinities with neighboring populations but also rare
      and ancient variation that suggests considerable isolation. This study
      investigates the skeletal phenotype of Andaman Islanders and Aeta foragers from
      the Philippines in the context of the phenotypic variation among other hunter
      gatherers globally, to test whether they show a common, unique physique apart
      from small body size. Particular emphasis is placed on the comparison of negrito
      phenotypes to African, Asian, and Australian hunter-gatherer diversity to
      investigate phenotypic similarities to other populations globally. The results
      demonstrate that despite sharing small adult stature, the Andaman Islanders and
      Aeta show variation in body dimensions. In particular, the Andaman Islanders
      share a pattern of narrow bi-iliac breadth and short upper limbs with the Khoisan
      (Later Stone Age Southern Africans), whereas the Aeta and Efe show broader bi
      iliac breadths relative to lower limb lengths. Although general similarities in
      size and proportions remain between the Andamanese and Aeta, differences in
      humero-femoral indices and arm length between these groups and the Efe
      demonstrate that there is not a generic "pygmy" phenotype. Our interpretations of
      negrito origins and adaptation must account for this phenotypic variation.

PMID- 24297222
TI  - Craniodental affinities of Southeast Asia's "negritos" and the concordance with
      their genetic affinities.
AB  - Genetic research into Southeast Asia's "negritos" has revealed their deep-rooted
      ancestry, with time depth comparable to that of Southwest Pacific populations.
      This finding is often interpreted as evidence that negritos, in contrast to other
      Southeast Asians, can trace much of their ancestry directly back to the early
      dispersal of Homo sapiens in the order of 70 kya from Africa to Pleistocene New
      Guinea and Australia. One view on negritos is to lump them and Southwest Pacific
      peoples into an "Australoid" race whose geographic distribution had included
      Southeast Asia prior to the Neolithic incursion of "Mongoloid" farmers. Studies
      into Semang osteology have revealed some hints of Southwest Pacific affinities in
      cranial shape, dental morphology, and dental metrical "shape." On the other hand,
      the Andamanese have been shown to resemble Africans in their craniometrics and
      South Asians in their dental morphology, while Philippine negritos resemble
      Mongoloid Southeast Asians in these respects and also in their dental metrics.
      This study expands the scope of negrito cranial comparisons by including Melayu
      Malays and additional coverage of South Asians. It highlights the distinction
      between the Mongoloid-like Philippine negritos and the Andamanese and Semang (and
      Senoi of Malaya) with their non-Mongoloid associations. It proposes that the
      early/mid-Holocene dispersal of the B4a1a mitochondrial DNA clade across Borneo,
      the Philippines, and Taiwan may be important for understanding the distinction
      between Philippine and other negritos. 

PMID- 24297223
TI  - Climate change influenced female population sizes through time across the
      Indonesian archipelago.
AB  - Lying at the crossroads of Asia and the Pacific world, the Indonesian archipelago
      hosts one of the world's richest accumulations of cultural, linguistic, and
      genetic variation. While the role of human migration into and around the
      archipelago is now known in some detail, other aspects of Indonesia's complex
      history are less understood. Here, we focus on population size changes from the
      first settlement of Indonesia nearly 50 kya up to the historic era. We
      reconstructed the past effective population sizes of Indonesian women using
      mitochondrial DNA sequences from 2,104 individuals in 55 village communities on
      four islands spanning the Indonesian archipelago (Bali, Flores, Sumba, and
      Timor). We found little evidence for large fluctuations in effective population
      size. Most communities grew slowly during the late Pleistocene, peaked 15-20 kya,
      and subsequently declined slowly into the Holocene. This unexpected pattern may
      reflect population declines caused by the flooding of lowland hunter/gatherer
      habitat during sea-level rises following the last glacial maximum. 

PMID- 24297224
TI  - The Andaman Islanders in a regional genetic context: reexamining the evidence for
      an early peopling of the archipelago from South Asia.
AB  - The indigenous inhabitants of the Andaman Islands were considered by many early
      anthropologists to be pristine examples of a "negrito" substrate of humanity that
      existed throughout Southeast Asia. Despite over 150 years of research and study,
      questions over the extent of shared ancestry between Andaman Islanders and other
      small-bodied, gracile, dark-skinned populations throughout the region are still
      unresolved. This shared phenotype could be a product of shared history,
      evolutionary convergence, or a mixture of both. Recent population genetic studies
      have tended to emphasize long-term physical isolation of the Andaman Islanders
      and an affinity to ancestral populations of South Asia. We reexamine the genetic
      evidence from genome-wide autosomal single-nucleotide polymorphism (SNP) data for
      a shared history between the tribes of Little Andaman (Onge) and Great Andaman,
      and between these two groups and the rest of South and Southeast Asia (both
      negrito and non-negrito groups). 

PMID- 24297225
TI  - Admixture patterns and genetic differentiation in negrito groups from West
      Malaysia estimated from genome-wide SNP data.
AB  - Southeast Asia houses various culturally and linguistically diverse ethnic
      groups. In Malaysia, where the Malay, Chinese, and Indian ethnic groups form the
      majority, there exist minority groups such as the "negritos" who are believed to
      be descendants of the earliest settlers of Southeast Asia. Here we report
      patterns of genetic substructure and admixture in two Malaysian negrito
      populations (Jehai and Kensiu), using ~50,000 genome-wide single-nucleotide
      polymorphism (SNP) data. We found traces of recent admixture in both the negrito
      populations, particularly in the Jehai, with the Malay through principal
      component analysis and STRUCTURE analysis software, which suggested that the
      admixture was as recent as one generation ago. We also identified significantly
      differentiated nonsynonymous SNPs and haplotype blocks related to intracellular
      transport, metabolic processes, and detection of stimulus. These results
      highlight the different levels of admixture experienced by the two Malaysian
      negritos. Delineating admixture and differentiated genomic regions should be of
      importance in designing and interpretation of molecular anthropology and disease
      association studies. 

PMID- 24297226
TI  - Genetic diversity of four Filipino negrito populations from Luzon: comparison of
      male and female effective population sizes and differential integration of
      immigrants into Aeta and Agta communities.
AB  - Genetic data corresponding to four negrito populations (two Aeta and two Agta; n
      = 120) from the Luzon region of the Philippines have been analyzed. These data
      comprise mitochondrial DNA (mtDNA) hypervariable segment 1 haplotypes and
      haplogroups, Y-chromosome haplogroups and short tandem repeats (STRs), autosomal
      STRs, and X-chromosome STRs. The genetic diversity and structure of the
      populations were investigated at a local, regional, and interregional level. We
      found a high level of autosomal differentiation, combined with no significant
      reduction in diversity, consistent with long-term settlement of the Luzon region
      by the ancestors of the Agta and Aeta followed by reduced gene flow between these
      two ethnolinguistic groups. Collectively, the Aeta have a much higher ratio of
      female:male effective population size than do the Agta, a finding that supports
      phylogenetic analysis of their mtDNA and Y-chromosome haplogroups, which suggests
      different genetic sex-biased contributions from putative Austronesian source
      populations. We propose that factors of social organization that led to the
      reduction in Agta female effective population size may also be linked to the
      limited incorporation of female lineages associated with the settlement of the
      Philippines by Austronesian speakers; conversely, the reduction in Aeta male
      effective population size, relative to females, could be indicative of a limited
      incorporation of male lineages associated with this demographic process. 

PMID- 24297227
TI  - Anthropology and GIS: temporal and spatial distribution of the Philippine negrito
      groups.
AB  - The Philippine "negrito" groups comprise a diverse group of populations speaking
      over 30 different languages, who are spread all over the archipelago, mostly in
      marginal areas of Luzon Island in the north, the central Visayas islands, and
      Mindanao in the south. They exhibit physical characteristics that are different
      from more than 100 Philippine ethnolinguistic groups that are categorized as non
      negritos. Given their numbers, it is not surprising that Philippine negritos make
      up a major category in a number of general ethnographic maps produced since the
      nineteenth century. Reports from various ethnological surveys during this period,
      however, have further enriched our understanding regarding the extent and
      distribution of negrito populations. Using the data contained in these reports,
      it is possible to plot and create a map showing the historical locations and
      distribution of negrito groups. Using geographic information systems (GIS), the
      location and distribution of negrito groups at any given time can be overlaid on
      historical or current maps. In the present study, a GIS layer was compiled and
      extracted from the 2000 Philippine Census of population at the village level and
      overlaid on existing complement ongoing anthropological and genetic studies of
      negrito groups that inhabit different locations within the Philippine
      archipelago. 

PMID- 24297228
TI  - Mount Pinatubo, inflammatory cytokines, and the immunological ecology of Aeta
      hunter-gatherers.
AB  - Early growth cessation and reproduction are predicted to maximize fitness under
      conditions of high adult mortality, factors that could explain the pygmy
      phenotype of many rainforest hunter-gatherers. This life-history hypothesis is
      elegant but contentious in part because it lacks a clear biological mechanism.
      One mechanism stems from the field of human immunological ecology and the concept
      of inflammation "memory" across the life cycle and into subsequent generations.
      Maternal exposures to disease can influence immunological cues present in breast
      milk; because maternal provisioning via lactation occurs during critical periods
      of development, it is plausible that these cues can also mediate early growth
      cessation and small body size. Such epigenetic hypotheses are difficult to test,
      but the concept of developmental programming is attractive because it could
      explain how the stature of a population can change over time, in terms of both
      secular increases and rapid intergenerational decreases. Here we explore this
      concept by focusing on the Aeta, a population of former hunter-gatherers, and the
      Ilocano, a population of rice farmers. We predicted that Aeta mothers would
      produce breast milk with higher concentrations of four bioactive factors due to
      high infectious burdens. Further, we predicted that the concentrations of these
      factors would be highest in the cohort of women born in the early 1990s, when
      exposure to infectious disease was acute following the eruption of Mount Pinatubo
      in June 1991. We analyzed levels of adiponectin, C-reactive protein, and
      epidermal growth factor in the milk of 24 Aeta and 31 Ilocano women and found no
      detectable differences, whereas levels of transforming growth factor-?2 were
      elevated among the Aeta, particularly as a function of maternal age. We found no
      difference between cohorts divided by the volcanic eruption (n = 43 born before,
      n = 12 born after). We discuss the implications of our findings for the terminal
      investment hypothesis and we suggest that the historical ecology of the Aeta is a
      promising model system for testing epigenetic hypotheses focused on the evolution
      of small body size. 

PMID- 24297229
TI  - Evolution of the pygmy phenotype: evidence of positive selection fro genome-wide
      scans in African, Asian, and Melanesian pygmies.
AB  - Human pygmy populations inhabit different regions of the world, from Africa to
      Melanesia. In Asia, short-statured populations are often referred to as
      "negritos." Their short stature has been interpreted as a consequence of
      thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical
      forests. A more recent hypothesis proposes that their stature is the outcome of a
      life history trade-off in high-mortality environments, where early reproduction
      is favored and, consequently, early sexual maturation and early growth cessation
      have coevolved. Some serological evidence of deficiencies in the growth
      hormone/insulin-like growth factor axis have been previously associated with
      pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype
      data, we first tested whether different negrito groups living in the Philippines
      and Papua New Guinea are closely related and then investigated genomic signals of
      recent positive selection in African, Asian, and Papuan pygmy populations. We
      found that negritos in the Philippines and Papua New Guinea are genetically more
      similar to their nonpygmy neighbors than to one another and have experienced
      positive selection at different genes. These results indicate that geographically
      distant pygmy groups are likely to have evolved their short stature
      independently. We also found that selection on common height variants is unlikely
      to explain their short stature and that different genes associated with growth,
      thyroid function, and sexual development are under selection in different pygmy
      groups. 

PMID- 24297230
TI  - Mountain pygmies of Western New Guinea: a morphological and molecular approach.
AB  - The presence of "pygmy" or pygmoid groups among New Guinea populations has been
      the object of scientific interest since the end of the nineteenth century.
      Morphological and molecular data are used here to study western New Guinea
      population variability, focusing in particular on two pygmoid groups living in
      the eastern fringe highlands of Papua: the Una and the Ketengban. Various kinds
      of anthropometric data are examined, as well as height, weight, and body mass
      index, to carry out comparisons with nearby ethnic groups living in the highland
      and lowland regions. The Ketengban data were also compared with other data
      recorded 20 years before. The results of previous research on the sequencing of
      the mitochondrial DNA hypervariable segment 1 region and nuclear DNA
      nonrecombining Y-chromosome polymorphisms are presented. Both morphological and
      molecular studies involve adult subjects of both genders, representative of the
      same ethnic groups and/or geographic regions. The pygmoid groups turn out to be
      significantly different from all other study groups, due to their small size, as
      confirmed by analysis of variance, although significant height and weight
      increments are observed with respect to those previously recorded. However,
      putative neutral genetic variation estimated from mitochondrial DNA and Y
      chromosome markers support a recent shared common history between these pygmoid
      populations and the other central Papua groups (except for the Dani-Lani). These
      findings suggest that the short-stature phenotype is an independent secondary
      adaptation, possibly driven by an iodine-deficient environment, which leaves the
      potential for further investigations. 

PMID- 24297231
TI  - Phenotypic plasticity of climbing-related traits in the ankle joint of great apes
      and rainforest hunter-gatherers.
AB  - The "negrito" and African "pygmy" phenotypes are predominately exhibited by
      hunter-gatherers living in rainforest habitats. Foraging within such habitats is
      associated with a unique set of locomotor behaviors, most notably habitual
      vertical climbing during the pursuit of honey, fruit, and game. When performed
      frequently, this behavior is expected to correlate with developmentally plastic
      skeletal morphologies that respond to mechanical loading. Using six measurements
      in the distal tibia and talus that discriminate nonhuman primates by vertical
      climbing frequency, we tested the prediction that intraspecific variation in this
      behavior is reflected in the morphology of the ankle joint of habitually climbing
      human populations. First, to explore the plasticity of climbing-linked
      morphologies, we made comparisons between chimpanzees, gorillas, and orangutans
      from wild and captive settings. The analysis revealed significant differences in
      two climbing-linked traits (anterior expansion of the articular surface of the
      distal tibia and increased degree of talar wedging), indicating that these traits
      are sensitive to climbing behavior. However, our analyses did not reveal any
      signatures of climbing behavior in the ankles of habitually climbing hunter
      gatherers. These results suggest that the detection of fine-grained differences
      in human locomotor behaviors at the ankle joint, particularly those associated
      with arboreality, may be obscured by the functional demands of terrestrial
      bipedalism. Accordingly, it may be difficult to use population-level
      characteristics of ankle morphology to make inferences about the climbing
      behavior of hominins in the fossil record, even when facultative arborealism is
      associated with key fitness benefits. 

PMID- 24297232
TI  - Who are the Philippine negritos? Evidence from language.
AB  - This article addresses the linguistic evidence from which details about
      Philippine "negritos" can be inferred. This evidence comes from the naming
      practices of both negrito and non-negrito peoples, from which it can be inferred
      that many negrito groups have maintained a unique identity distinct from other
      groups since the dispersal of Malayo-Polynesian languages. Other names, such as
      Dupaningan and Dumagat, reference locations, from which it is assumed the
      negritos left after contact with Malayo-Polynesian people. Evidence also comes
      from the relative positions of negrito groups vis-a-vis other groups within the
      subfamily with which their current language can be grouped. Many of these
      languages can be shown to be first order branches, suggesting early separation
      from the people whose languages they first acquired. The geospatial distribution
      of the northern languages of the Philippines closely matches the proposed
      dispersal routes of early Malayo-Polynesian peoples into the Cagayan River Valley
      and up the Chico and Magat tributaries from which negrito groups were displaced.
      One lexical item that is discussed is the word for the traditionally widespread
      practice of head-hunting, the term for which is reconstructible to Proto
      Austronesian with reflexes throughout the Philippines and countries to the south.
      The practice was probably associated with agriculture and not only may have
      contributed to the early rapid spread south of Malayo-Polynesian languages
      through the Philippines and ultimately into the Pacific but also was later a
      major factor in the long periods of isolation of negrito peoples, during which
      the languages they had first acquired became very different from that of their
      former neighbors. 

PMID- 24297233
TI  - Kinship matters: structures of alliance, indigenous foragers, and the
      Austronesian diaspora.
AB  - The study of kinship systems has direct relevance for the field of human genetics
      and the study of microevolution in human populations. Some types of postmarital
      residence rules--rules requiring a married couple to live with or near relatives
      of the husband or wife--will have consequences for the distribution of
      mitochondrial DNA and Y chromosome lineages. Rules that proscribe or encourage
      marriage with close kin will also have consequences for allele frequency. A
      preference for marrying at a distance, both socially and geographically, creates
      alliances that can have survival value for individuals and groups in an
      environment of periodic or unpredictable scarcity. This article considers the
      nature of early contact between the indigenous foraging populations of the
      Philippines and Austronesian speaking settlers who began arriving ~4,500-4,000
      BP. It argues that when the first Austronesians arrived they brought with them a
      kinship system based on symmetrical exchange between descent-based groups. It
      considers why such a system was gradually changed into the bilateral kinship
      systems that characterize the various peoples of the Philippines today, "negrito"
      and non-negrito alike.

PMID- 24297234
TI  - Time and place in the prehistory of the Aslian languages.
AB  - The Aslian language family, located in the Malay Peninsula and southern Thai
      Isthmus, consists of four distinct branches comprising some 18 languages. These
      languages predate the now dominant Malay and Thai. The speakers of Aslian
      languages exhibit some of the highest degree of phylogenetic and societal
      diversity present in Mainland Southeast Asia today, among them a foraging
      tradition particularly associated with locally ancient, Pleistocene genetic
      lineages. Little advance has been made in our understanding of the linguistic
      prehistory of this region or how such complexity arose. In this article we
      present a Bayesian phylogeographic analysis of a large sample of Aslian
      languages. An explicit geographic model of diffusion is combined with a cognate
      birth-word death model of lexical evolution to infer the location of the major
      events of Aslian cladogenesis. The resultant phylogenetic trees are calibrated
      against dates in the historical and archaeological record to infer a detailed
      picture of Aslian language history, addressing a number of outstanding questions,
      including (1) whether the root ancestor of Aslian was spoken in the Malay
      Peninsula, or whether the family had already divided before entry, and (2) the
      dynamics of the movement of Aslian languages across the peninsula, with a
      particular focus on its spread to the indigenous foragers. 

PMID- 24297235
TI  - Terror from the sky: unconventional linguistic clues to the negrito past.
AB  - Within recorded history, most Southeast Asian peoples have been of "southern
      Mongoloid" physical type, whether they speak Austroasiatic, Tibeto-Burman,
      Austronesian, Tai-Kadai, or Hmong-Mien languages. However, population
      distributions suggest that this is a post-Pleistocene phenomenon and that for
      tens of millennia before the last glaciation ended Greater Mainland Southeast
      Asia, which included the currently insular world that rests on the Sunda Shelf,
      was peopled by short, dark-skinned, frizzy-haired foragers whose descendants in
      the Philippines came to be labeled by the sixteenth-century Spanish colonizers as
      "negritos," a term that has since been extended to similar groups throughout the
      region. There are three areas in which these populations survived into the
      present so as to become part of written history: the Philippines, the Malay
      Peninsula, and the Andaman Islands. All Philippine negritos speak Austronesian
      languages, and all Malayan negritos speak languages in the nuclear Mon-Khmer
      branch of Austroasiatic, but the linguistic situation in the Andamans is a world
      apart. Given prehistoric language shifts among both Philippine and Malayan
      negritos, the prospects of determining whether disparate negrito populations were
      once a linguistically or culturally unified community would appear hopeless.
      Surprisingly, however, some clues to a common negrito past do survive in a most
      unexpected way. 

PMID- 24297236
TI  - Making friends in the rainforest: "negrito" adaptation to risk and uncertainty.
AB  - The so-called negritos adapt not just to a tropical forest environment but also
      to an environment characterized by perturbations and fluctuations. As with other
      hunter-gatherers in the region and, indeed, throughout the world, they use both
      social and ecological methods to enhance their chances of survival in this
      changing environment: socially, they have developed networks of trading and
      marriage partners; ecologically, they maintain patches of key resources that are
      available for future harvesting. As evidenced in the case of the Batek (Orang
      Asli), patterns of forest structure and composition are sometimes direct outcomes
      of intentional resource concentration and enrichment strategies. While little of
      the above is controversial anthropologically, what has drawn some debate is the
      nature of the relationship with partner societies. Conventional wisdom posits
      relations of inequality between foragers and "others": foragers and farmers are
      often construed as hierarchical dyads where foragers supply products or labor to
      farmers in exchange for agricultural harvests and other trade goods. This kind of
      adaptation appears to be one of divergent specialization. However, there are
      cases, such as in the relationship between Batek and Semaq Beri, where both
      societies follow a roughly similar mode of adaptation, and specialization has not
      materialized. In sum, while not denying that hierarchy and inequality exist, I
      suggest that they have to be contextualized within a larger strand of
      relationships that includes both hierarchy and egality. Further, such
      relationships are part of the general portfolio of risk reduction strategies,
      following which access to widely scattered environmental resources, and passage
      from one location to another, is enhanced not by competing with and displacing
      neighbors but by maintaining a flexible regime of friendly exchange partners. 

PMID- 24297237
TI  - Why have the peninsular "negritos" remained distinct?
AB  - The primary focus of this article is on the so-called negritos of Peninsular
      Malaysia and southern Thailand, but attention is also paid to other parts of
      Southeast Asia. I present a survey of current views on the "negrito" phenotype-
      is it single or many? If the phenotype is many (as now seems likely), it must
      have resulted from parallel evolution in the several different regions where it
      has been claimed to exist. This would suggest (contrary to certain views that
      have been expressed on the basis of very partial genetic data) that the phenotype
      originated recently and by biologically well-authenticated processes from within
      the neighboring populations. Whole-genome and physical-anthropological research
      currently support this view. Regardless of whether the negrito phenotype is
      ancient or recent-and to the extent that it retains any valid biological reality
      (which is worth questioning)-explanations are still needed for its continued
      distinctiveness. In the Malay Peninsula, a distinctive "Semang" societal pattern
      followed by most, but not all, so-called negritos may have been responsible for
      this by shaping familial, breeding, and demographic patterns to suit the two main
      modes of environmental appropriation that they have followed, probably for some
      millennia: nomadic foraging in the forest, and facultative dependence on exchange
      or labor relations with neighboring populations. The known distribution of
      "negritos" in the Malay Peninsula is limited to areas within relatively easy
      reach of archaeologically authenticated premodern transpeninsular trading and
      portage routes, as well as of other non-negrito, Aslian-speaking populations
      engaged in swidden farming. This suggests that their continued distinctiveness
      has resulted from a wish to maintain a complementary advantage vis-a-vis other,
      less specialized populations. Nevertheless, a significant degree of discordance
      exists between the associated linguistic, societal-tradition, and biological
      patterns which suggests that other factors have also been at play.

PMID- 24297238
TI  - Brief communication: the Australian Barrineans and their relationship to
      Southeast Asian negritos: an investigation using mitochondrial genomics.
AB  - The existence of a short-statured Aboriginal population in the Far North
      Queensland (FNQ) rainforest zone of Australia's northeast coast and Tasmania has
      long been an enigma in Australian anthropology. Based on their reduced stature
      and associated morphological traits such as tightly curled hair, Birdsell and
      Tindale proposed that these "Barrinean" peoples were closely related to "negrito"
      peoples of Southeast Asia and that their ancestors had been the original
      Pleistocene settlers of Sahul, eventually displaced by taller invaders.
      Subsequent craniometric and blood protein studies, however, have suggested an
      overall homogeneity of indigenous Australians, including Barrineans. To confirm
      this finding and determine the degree of relatedness between Barrinean people and
      Southeast Asian negritos, we compared indigenous Australian mitochondrial DNA
      (mtDNA) sequences in populations from the FNQ rainforest ecozone and Tasmania
      with sequences from other Australian Aboriginal populations and from Southeast
      Asian negrito populations (Philippines Batek and Mamanwa, and mainland Southeast
      Asian Jahai, Mendriq, and Batak). The results confirm that FNQ and Tasmanian
      mtDNA haplogroups cluster with those of other Australian Aboriginal populations
      and are only very distantly related to Southeast Asian negrito haplogroups. 

PMID- 24297239
TI  - Concluding remarks: what's in a name? "Negritos" in the context of the human
      prehistory of Southeast Asia.
AB  - The "negrito" hypothesis posits that various indigenous groups throughout Island
      and Mainland Southeast Asia have a shared phenotype due to common descent from a
      putative ancestral population, representing a pre-agricultural substrate of
      humanity in the region. This has been examined and tested many times in the past,
      with no clear resolution. With many new resources to hand, the articles in this
      volume reexamine this hypothesis in a range of different ways. The evidence
      presented in this double issue of Human Biology speaks more against the category
      of "negrito" than for it. While populations with the negrito phenotype form a
      small proportion of all contemporary populations in this region, they have
      remained a persistent presence. And without a fascination about their origins,
      there would not be such a depth of knowledge about the human biology of this
      region more broadly as there is now.

PMID- 24297242
TI  - Teen with lesion on nasal sidewall.

PMID- 24297245
TI  - Posttraumatic stress in children.

PMID- 24297246
TI  - Rearrangements of chromosome bands 15q12-q21 are secondary to HMGA2 deregulation
      in conventional lipoma.
AB  - Rearrangements of chromosome arm 15q are rare but recurrent in conventional
      lipomas, a tumor type often showing deregulated expression of the HMGA2 gene. In
      order to assess whether 15q rearrangements could constitute a distinct
      pathogenetic mechanism, we studied seven cases of conventional lipoma that at G
      banding analysis had various rearrangements of 15q12-q21. The breakpoints in 15q
      were mapped by fluorescence in situ hybridization (FISH) and single nucleotide
      polymorphism array analyses, and the status of the HMGA2 gene was evaluated by
      FISH and/or quantitative PCR. We found an overlapping deletion on 15q in two
      cases, but no recurring breakpoint among the other cases. In addition, all cases
      displayed rearrangement of HMGA2 at the genomic or the transcriptional level.
      Although 15q rearrangements sometimes are noted as the sole aberration at
      cytogenetic analysis of conventional lipomas, they are secondary to HMGA2
      deregulation. 

PMID- 24297247
TI  - Cancer risk communication, predictive testing and management in France, Germany,
      the Netherlands and the UK: general practitioners' and breast surgeons' current
      practice and preferred practice responsibilities.
AB  - Genetic testing has its greatest public health value when it identifies
      individuals who will benefit from specific interventions based upon their risk.
      This paradigm is the basis for the use of predictive tests, such as BRCA1/BRCA2
      testing which has become part of clinical practice for more than a decade.
      Currently predictive BRCA1/BRCA2 testing is offered to women using low, moderate
      and high risk based upon family history as cut-off levels. Non-genetic health
      professionals such as general practitioners (GPs) and breast surgeons (BS) are
      seen as gatekeepers to manage demand and/or facilitate access to appropriate
      services for high-risk patients. Data about current practices are lacking. The
      paper presents data on the current practice of GPs' and BS' cancer risk
      assessment, referral practices and preferred practice responsibilities for women
      at risk for familial breast cancer in France, Germany, the Netherlands and the UK
      derived by a self-administered questionnaire send to a representative sample of
      GPs and BS in the four countries. One thousand one hundred ninety-seven GPs and
      1,223 BS completed the questionnaire. Both GPs and BS reported that they are
      consulted by a considerable number of patients presenting with concerns about a
      family history of cancer. Both commonalities and striking differences could be
      observed between GPs and BS from the four participating countries. GPs from
      France and Germany reported significantly higher proportions taking a family
      history of cancer including the extended family than GPs from the Netherlands and
      the UK. Most GPs from France, Germany and the Netherlands stated their
      willingness for providing risk assessment for an unaffected (high-risk) woman
      with a family history of breast cancer and the vast majority of BS from all four
      countries reported that they themselves would provide risk assessment for an
      unaffected (high-risk) woman with a family history of breast cancer. However, a
      substantial number of both GPs and BS would not have taken an appropriate family
      history for their patient failing to take into account the paternal side of the
      family. GPs from Germany reported a significantly lower readiness to refer a
      patient with a family history of a BRCA1 mutation for specialist genetic
      counselling when compared to the GPs from the other countries. GPs and BS from
      France, Germany and the Netherlands significantly less often assigned practice
      responsibilities to a genetic specialist as compared to the participating GPs and
      BS from the UK. The outcome of the study confirms the need for capability
      building in genetics for non-genetic health professionals. Using genetic risk
      assessment tools without a full understanding could result in missed
      opportunities for cancer prevention and harm patients. In order to provide best
      possible services for high-risk patients presenting with cancer concerns, close
      collaboration with clinical geneticists should become routine part of mainstream
      medical practice. 

PMID- 24297248
TI  - Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi-1
      leukemia cells.
AB  - Histone deacetylase (HDAC) inhibitors have been reported to inhibit tumor
      angiogenesis via the downregulation of angiogenic factors. Our previous in vitro
      studies demonstrated that valproic acid (VPA) exerted antitumor effects on Kasumi
      1 cells, which are human acute myeloid leukemia cells with an 8;21 chromosome
      translocation. In the present study, the effects of VPA on tumor angiogenesis
      were investigated in mice transplanted with Kasumi-1 cells. Semi-quantitative
      reverse transcription-polymerase chain reaction, western blotting and
      immunohistochemistry were used to detect the expression of vascular endothelial
      growth factor (VEGF), VEGF receptor (VEGFR2) and basic fibroblast growth factor
      (bFGF). The tumor microvessel density was measured following staining with an
      anti-CD34 antibody. Chromatin immunoprecipitation was used to study the effect of
      VPA-induced histone hyperacetylation on VEGF transcription. An intraperitoneal
      injection of VPA inhibited tumor growth and angiogenesis in mice transplanted
      with Kasumi-1 cells. The mRNA and protein expression of VEGF, VEGFR2 and bFGF
      were inhibited by VPA treatment. In addition, VPA downregulated HDAC, increased
      histone H3 acetylation and enhanced the accumulation of hyperacetylated histone
      H3 on the VEGF promoters. The findings of the present study indicate that VPA, an
      HDAC inhibitor, exerts an antileukemic effect through an anti-angiogenesis
      mechanism. In conclusion, the mechanism underlying VPA-induced anti-angiogenesis
      is associated with the suppression of angiogenic factors and their receptors. VPA
      may increase the accumulation of acetylated histones on the VEGF promoters, which
      possibly contributes to the regulation of angiogenic factors.

PMID- 24297249
TI  - Identification of small molecule NPR-B antagonists by high throughput screening-
      potential use in heart failure.
AB  - We found previously that stimulation of natriuretic peptide receptor (NPR)-B by C
      type natriuretic peptide (CNP) in failing rat ventricle potentiates beta1
      adrenoceptor (beta1-AR)-mediated inotropic response to noradrenaline through cGMP
      mediated inhibition of phosphodiesterase (PDE) 3, thereby enhancing cAMP-mediated
      signalling. Increased cAMP-mediated signalling is deleterious in chronic heart
      failure (HF; basis for the use of beta-blockers in HF) and we propose to consider
      NPR-B antagonists as new HF treatment in addition to conventional therapy. Since
      there is no NPR-B-selective antagonist available for clinical studies, we aimed
      at identifying a novel small molecule (non-peptide) NPR-B antagonist. An assay
      was developed and high throughput screening performed on a chemical library of
      about 20,000 small molecule compounds (<500 Da) to identify NPR-B antagonists
      based on inhibition of CNP-stimulated cGMP production in NPR-B-expressing HEK293
      cells. The screen revealed several potential NPR-B antagonists, of which six were
      selected for further studies. Three showed selective NPR-B vs NPR-A inhibition
      and three were partially selective. The compounds mediated reversible,
      noncompetitive inhibition and most likely act as allosteric modulators binding
      outside the agonist binding site of NPR-B. In rat ventricular muscle strips, the
      potentiating effect of CNP upon beta1-AR-evoked inotropic effects could be
      attenuated by at least one of these compounds. We identified several small
      molecule NPR-B antagonists by high throughput screening and show in a functional
      heart preparation that blocking NPR-B stimulation with a small molecule compound
      can reduce the potentiating effect of CNP on the beta1-AR-mediated inotropic
      response to noradrenaline. 

PMID- 24297250
TI  - Faradaic efficiency of O2 evolution on metal nanoparticle sensitized hematite
      photoanodes.
AB  - Functionalization of transition metal oxides using metallic nanoparticles is an
      interesting route towards efficient photoelectrochemical hydrogen production via
      water splitting. Although an enhanced photocurrent in photoanodes upon
      functionalization with metallic nanostructures has been observed in several
      studies, to the best of our knowledge no measurements of the Faradaic efficiency
      (FE) of the oxygen evolution reaction (OER) have been reported for such systems.
      This work characterizes the FE on a model system consisting of ultra-thin films
      of hematite (Fe2O3) sensitized with Ti/Au nanodisks. Compared to bare hematite
      references, sensitized samples showed significantly enhanced photocurrents as
      well as O2 evolution. Experimental evidence suggests that the observed
      enhancement was not due to photocatalytic activity of the nanodisks. The FE has
      been determined to be 100%, within the experimental errors, for both sensitized
      and reference samples. Also, this work demonstrates that the sensitized samples
      were stable for at least 16 hours photocurrent testing. The concepts shown in
      this work are generally applicable to any situation in which a semiconductor has
      its water splitting performance enhanced by metallic nanostructures. 

PMID- 24297251
TI  - starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction
      networks from large-scale CLIP-Seq data.
AB  - Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs,
      pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been
      implicated in cell-fate determination and in various human diseases, surprisingly
      little is known about the regulatory interaction networks among the multiple
      classes of RNAs. In this study, we developed starBase v2.0
      (http://starbase.sysu.edu.cn/) to systematically identify the RNA-RNA and protein
      RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH)
      data sets generated by 37 independent studies. By analyzing millions of RNA
      binding protein binding sites, we identified ~9000 miRNA-circRNA, 16 000 miRNA
      pseudogene and 285,000 protein-RNA regulatory relationships. Moreover, starBase
      v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally
      supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified
      ~10,000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13
      functional genomic annotations, we developed miRFunction and ceRNAFunction web
      servers to predict the function of miRNAs and other ncRNAs from the miRNA
      mediated regulatory networks. Finally, we developed interactive web
      implementations to provide visualization, analysis and downloading of the
      aforementioned large-scale data sets. This study will greatly expand our
      understanding of ncRNA functions and their coordinated regulatory networks.

PMID- 24297252
TI  - eggNOG v4.0: nested orthology inference across 3686 organisms.
AB  - With the increasing availability of various 'omics data, high-quality orthology
      assignment is crucial for evolutionary and functional genomics studies. We here
      present the fourth version of the eggNOG database (available at
      http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from
      complete genomes, and then applies a comprehensive characterization and analysis
      pipeline to the resulting gene families. Compared with the previous version, we
      have more than tripled the underlying species set to cover 3686 organisms,
      keeping track with genome project completions while prioritizing the inclusion of
      high-quality genomes to minimize error propagation from incomplete proteome sets.
      Major technological advances include (i) a robust and scalable procedure for the
      identification and inclusion of high-quality genomes, (ii) provision of
      orthologous groups for 107 different taxonomic levels compared with 41 in
      eggNOGv3, (iii) identification and annotation of particularly closely related
      orthologous groups, facilitating analysis of related gene families, (iv)
      improvements of the clustering and functional annotation approach, (v) adoption
      of a revised tree building procedure based on the multiple alignments generated
      during the process and (vi) implementation of quality control procedures
      throughout the entire pipeline. As in previous versions, eggNOGv4 provides
      multiple sequence alignments and maximum-likelihood trees, as well as broad
      functional annotation. Users can access the complete database of orthologous
      groups via a web interface, as well as through bulk download. 

PMID- 24297253
TI  - MycoCosm portal: gearing up for 1000 fungal genomes.
AB  - MycoCosm is a fungal genomics portal (http://jgi.doe.gov/fungi), developed by the
      US Department of Energy Joint Genome Institute to support integration, analysis
      and dissemination of fungal genome sequences and other 'omics' data by providing
      interactive web-based tools. MycoCosm also promotes and facilitates user
      community participation through the nomination of new species of fungi for
      sequencing, and the annotation and analysis of resulting data. By efficiently
      filling gaps in the Fungal Tree of Life, MycoCosm will help address important
      problems associated with energy and the environment, taking advantage of growing
      fungal genomics resources. 

PMID- 24297254
TI  - Structure and DNA-binding properties of the Bacillus subtilis SpoIIIE DNA
      translocase revealed by single-molecule and electron microscopies.
AB  - SpoIIIE/FtsK are a family of ring-shaped, membrane-anchored, ATP-fuelled motors
      required to segregate DNA across bacterial membranes. This process is directional
      and requires that SpoIIIE/FtsK recognize highly skewed octameric sequences
      (SRS/KOPS for SpoIIIE/FtsK) distributed along the chromosome. Two models have
      been proposed to explain the mechanism by which SpoIIIE/FtsK interact with DNA.
      The loading model proposes that SpoIIIE/FtsK oligomerize exclusively on SpoIIIE
      recognition sequence/orienting polar sequences (SRS/KOPS) to accomplish
      directional DNA translocation, whereas the target search and activation mechanism
      proposes that pre-assembled SpoIIIE/FtsK hexamers bind to non-specific DNA, reach
      SRS/KOPS by diffusion/3d hopping and activate at SRS/KOPS. Here, we employ single
      molecule total internal reflection imaging, atomic force and electron
      microscopies and ensemble biochemical methods to test these predictions and
      obtain further insight into the SpoIIIE-DNA mechanism of interaction. First, we
      find that SpoIIIE binds DNA as a homo-hexamer with neither ATP binding nor
      hydrolysis affecting the binding mechanism or affinity. Second, we show that
      hexameric SpoIIIE directly binds to double-stranded DNA without requiring the
      presence of SRS or free DNA ends. Finally, we find that SpoIIIE hexamers can show
      open and closed conformations in solution, with open-ring conformations most
      likely resembling a state poised to load to non-specific, double-stranded DNA.
      These results suggest how SpoIIIE and related ring-shaped motors may be split
      open to bind topologically closed DNA. 

PMID- 24297255
TI  - iPfam: a database of protein family and domain interactions found in the Protein
      Data Bank.
AB  - The database iPfam, available at http://ipfam.org, catalogues Pfam domain
      interactions based on known 3D structures that are found in the Protein Data
      Bank, providing interaction data at the molecular level. Previously, the iPfam
      domain-domain interaction data was integrated within the Pfam database and
      website, but it has now been migrated to a separate database. This allows for
      independent development, improving data access and giving clearer separation
      between the protein family and interactions datasets. In addition to domain
      domain interactions, iPfam has been expanded to include interaction data for
      domain bound small molecule ligands. Functional annotations are provided from
      source databases, supplemented by the incorporation of Wikipedia articles where
      available. iPfam (version 1.0) contains >9500 domain-domain and 15 500 domain
      ligand interactions. The new website provides access to this data in a variety of
      ways, including interactive visualizations of the interaction data. 

PMID- 24297256
TI  - NCBI's Database of Genotypes and Phenotypes: dbGaP.
AB  - The Database of Genotypes and Phenotypes (dbGap, http://www.ncbi.nlm.nih.gov/gap)
      is a National Institutes of Health-sponsored repository charged to archive,
      curate and distribute information produced by studies investigating the
      interaction of genotype and phenotype. Information in dbGaP is organized as a
      hierarchical structure and includes the accessioned objects, phenotypes (as
      variables and datasets), various molecular assay data (SNP and Expression Array
      data, Sequence and Epigenomic marks), analyses and documents. Publicly accessible
      metadata about submitted studies, summary level data, and documents related to
      studies can be accessed freely on the dbGaP website. Individual-level data are
      accessible via Controlled Access application to scientists across the globe. 

PMID- 24297257
TI  - NECTAR: a database of codon-centric missense variant annotations.
AB  - NECTAR (Non-synonymous Enriched Coding muTation ARchive;
      http://nectarmutation.org) is a database and web application to annotate disease
      related and functionally important amino acids in human proteins. A number of
      tools are available to facilitate the interpretation of DNA variants identified
      in diagnostic or research sequencing. These typically identify previous reports
      of DNA variation at a given genomic location, predict its effects on transcript
      and protein sequence and may predict downstream functional consequences. Previous
      reports and functional annotations are typically linked by the genomic location
      of the variant observed. NECTAR collates disease-causing variants and
      functionally important amino acid residues from a number of sources. Importantly,
      rather than simply linking annotations by a shared genomic location, NECTAR
      annotates variants of interest with details of previously reported variation
      affecting the same codon. This provides a much richer data set for the
      interpretation of a novel DNA variant. NECTAR also identifies functionally
      equivalent amino acid residues in evolutionarily related proteins (paralogues)
      and, where appropriate, transfers annotations between them. As well as accessing
      these data through a web interface, users can upload batches of variants in
      variant call format (VCF) for annotation on-the-fly. The database is freely
      available to download from the ftp site: ftp://ftp.nectarmutation.org. 

PMID- 24297258
TI  - Lactational exposure of phthalate impairs insulin signaling in the cardiac muscle
      of F1 female albino rats.
AB  - Di-2-ethylhexyl phthalate (DEHP), a ubiquitous endocrine disruptor and
      plasticizer of polyvinyl chloride, is being used in the manufacture of consumer
      and medical products as well as in children's toys. Fetuses and newborns are more
      sensitive to endocrine disruption. DEHP is a lipophilic substance, which could
      easily be transferred to the developing offspring through placenta or breast
      milk. DEHP alters the metabolism of the endocrine organs, which leads to energy
      imbalance associated with increased risk of insulin resistance, obesity and
      cardiovascular disease. The heart is an insulin-responsive organ. The effect of
      DEHP on the cardiac muscle insulin signaling remains obscure. Since the
      developmental period is more vulnerable to the adverse effect of DEHP, the
      present study was framed to study the impact of lactational exposure of DEHP on
      insulin signaling molecules in the cardiac muscle of F1 progeny female albino rat
      (postnatal day 60). Healthy dams were treated with DEHP orally (0, 1, 10 and 100
      mg/kg body weight/day, respectively) from the postpartum day 1-21. Both low and
      high doses are relevant to the human exposure, and hence, both were used in this
      study. At a low dose (1 mg/kg body weight/day), obvious differences were observed
      in the fasting blood glucose and the insulin signaling molecule when compared to
      control. But marked differences were observed in the cardiac tissue insulin
      signaling molecules of animals treated with high doses. In conclusion, the DEHP
      treatment significantly increased the fasting blood glucose level and decreased
      the insulin receptor (IR), insulin receptor substrate (IRS-1), p-IRS-1(Tyr632), p
      Akt(Ser473), plasma membrane glucose transporter (GLUT4), (14)C-2-deoxyglucose
      uptake and the (14)C-glucose oxidation. Conversely, Akt and GLUT4 protein in
      cytosol remained unaltered compared to control. Lactational exposure of DEHP
      impairs insulin signal transduction and glucose oxidation in the cardiac muscle
      of the F1 female albino rats, suggesting its possible role in the development of
      type 2 diabetes. 

PMID- 24297259
TI  - QT dispersion and prognostication of the outcome in acute cardiotoxicities: A
      comparison with SAPS II and APACHE II scoring systems.
AB  - We aimed to evaluate the efficacy of QT dispersion (QTD) in determining the
      outcome of the patients poisoned by cardiotoxic medications and toxins. Patients
      who referred to our emergency department (ED) due to acute toxicity with any
      cardiotoxic medication or toxin and were admitted to medical toxicology intensive
      care unit (MTICU) were enrolled into the study. A questionnaire containing the
      demographic characteristics, vital signs, laboratory tests, electrocardiographic
      (ECG) parameters of the first ECG taken on MTICU or ED admission, simplified
      acute physiology score (SAPS), and acute physiology and chronic health evaluation
      (APACHE) score was filled for every single patient. QTD was manually calculated.
      The patients were divided into two groups of survivors and non-survivors and
      compared. Although QTD was not significantly different between the survivors and
      non-survivors (P = 0.8), SAPS II and APACHE II score were so. SAPS and APACHE had
      the highest sensitivity and specificity in determining the patients' mortality,
      respectively. SAPS had the highest sensitivity, and QTD had the highest
      specificity in predicting the later development of the complications. SAPS II and
      APACHE II scoring systems are the best systems for prognostication of death in
      patients with acute cardiotoxic medication-induced poisonings. QTD can be
      successfully used for the prediction of complications.

PMID- 24297260
TI  - Preventive effect of total flavones of Choerospondias axillaries on
      ischemia/reperfusion-induced myocardial infarction-related MAPK signaling
      pathway.
AB  - Choerospondias axillaris (Guangzao) is a medicinal plant used in Mongolia, and
      its fruit is commonly used for the treatment of cardiovascular diseases in
      clinic. The constituents responsible for this effect are always conceded to be
      the total flavonoids of C. axillaries (TFC). The present study was to evaluate
      the preventive effect of TFC on acute myocardial infarction induced by
      ischemia/reperfusion (I/R) in rats and the possible signaling pathway involved.
      The model of myocardial I/R was caused by occlusion of the left anterior
      descending coronary artery for 30 min followed by reperfusion for 2 h. Cardiac
      dysfunction, infarct size, pathologic histology and apoptosis were examined.
      Heart tissues were homogenized for biochemistry assays and Western blots
      analysis. The results indicated that pretreatment with TFC strongly improved
      cardiac function, obviously reduced heart pathologic lesion in I/R rat hearts.
      TFC also could protect the heart from I/R injury by increasing the levels of
      catalase, glutathione peroxidase and superoxide dismutase in heart homogenate,
      and decreasing that of malondialdehyde level. These beneficial effects were
      associated with the decrease in TUNEL-positive nuclear staining, Bax and caspase
      3 levels, and the increase in Bcl-2 expression. Moreover, TFC counteracted the
      I/R-induced decreased activation of p38 mitogen-activated protein kinase (MAPK)
      and Jun N-terminal kinase. These data suggested that TFC improved I/R-induced
      myocardium impairment via anti-oxidative and anti-apoptotic activities, and this
      beneficial effects were intervened by MAPK signaling pathway.

PMID- 24297261
TI  - Hearing impairment in hypothyroid dwarf mice caused by mutations of the thyroid
      peroxidase gene.
AB  - Thyroid hormone (TH) is essential for proper cochlear development and function,
      and TH deficiencies cause variable hearing impairment in humans and mice. Thyroid
      peroxidase (TPO) catalyzes key reactions in TH synthesis, and TPO mutations have
      been found to underlie many cases of congenital hypothyroidism in human patients.
      In contrast, only a single mutation of the mouse TPO gene has been reported
      previously (Tpo(R479C)) but was not evaluated for auditory function. Here, we
      describe and characterize two new mouse mutations of Tpo with an emphasis on
      their associated auditory deficits. Mice homozygous for these recessive mutations
      have dysplastic thyroid glands and lack detectable levels of TH. Because of the
      small size of mutant mice, the mutations were named teeny (symbol Tpo(tee)) and
      teeny-2 Jackson (Tpo(tee-2J)). Tpo(tee) is a single base-pair missense mutation
      that was induced by ENU, and Tpo(tee-2J) is a 64 bp intragenic deletion that
      arose spontaneously. The Tpo(tee) mutation changes the codon for a highly
      conserved tyrosine to asparagine (p.Y614N), and the Tpo(tee-2J) mutation deletes
      a splice donor site, which results in exon skipping and aberrant transcripts.
      Mutant mice are profoundly hearing impaired with auditory brainstem response
      (ABR) thresholds about 60 dB above those of non-mutant controls. The maturation
      of cochlear structures is delayed in mutant mice and tectorial membranes are
      abnormally thick. To evaluate the effect of genetic background on auditory
      phenotype, we produced a C3.B6-Tpo(tee-2J) congenic strain and found that ABR
      thresholds of mutant mice on the C3H/HeJ strain background are 10-12 dB lower
      than those of mutant mice on the C57BL/6 J background. The Tpo mutant strains
      described here provide new heritable mouse models of congenital hypothyroidism
      that will be valuable for future studies of thyroid hormones' role in auditory
      development and function.

PMID- 24297262
TI  - Input-output functions of vestibular afferent responses to air-conducted clicks
      in rats.
AB  - Sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid
      muscles (the cervical vestibular-evoked myogenic potential or cVEMP) and the
      extraocular muscles (the ocular VEMP or oVEMP) have proven useful in clinical
      assessment of vestibular function. VEMPs are commonly interpreted as a test of
      saccular function, based on neurophysiological evidence showing activation of
      saccular afferents by intense acoustic click stimuli. However, recent
      neurophysiological studies suggest that the clicks used in clinical VEMP tests
      activate vestibular end organs other than the saccule. To provide the neural
      basis for interpreting clinical VEMP testing results, the present study examined
      the extent to which air-conducted clicks differentially activate the various
      vestibular end organs at several intensities and durations in Sprague-Dawley
      rats. Single unit recordings were made from 562 vestibular afferents that
      innervated the otoliths [inferior branch otolith (IO) and superior branch otolith
      (SO)], the anterior canal (AC), the horizontal canal (HC), and the posterior
      canal (PC). Clicks higher than 60 dB SL (re-auditory brainstem response
      threshold) activated both semicircular canal and otolith organ afferents. Clicks
      at or below 60 dB SL, however, activated only otolith organ afferents. Longer
      duration clicks evoked larger responses in AC, HC, and SO afferents, but not in
      IO afferents. Intra-axonal recording and labeling confirmed that sound sensitive
      vestibular afferents innervated the horizontal and anterior canal cristae as well
      as the saccular and utricular maculae. Interestingly, all sound sensitive
      afferents are calyx-bearing fibers. These results demonstrate stimulus-dependent
      acoustic activation of both semicircular canals and otolith organs, and suggest
      that sound activation of vestibular end organs other than the saccule should not
      be ruled out when designing and interpreting clinical VEMP tests.

PMID- 24297263
TI  - Protective effect of metformin against cisplatin-induced ototoxicity in an
      auditory cell line.
AB  - Metformin, an antidiabetic drug with potent anticancer activity, is known to
      prevent oxidative stress-induced cell death in several cell types through a
      mechanism dependent on the mitochondria. In the present study, we investigated
      the influence of metformin on cisplatin ototoxicity in an auditory cell line.
      Cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliumbromide (Sigma, St. Louis, MO, USA) cell proliferation assay.
      Oxidative stress and apoptosis were assessed by flow cytometry analysis, Hoechst
      33258 staining, reactive oxygen species (ROS) measurement, and western blotting.
      Intracellular calcium concentration changes were detected using calcium imaging.
      Pretreatment with 1 mM metformin prior to the application of 20 MUM cisplatin
      significantly decreased the frequency of late apoptosis in HEI-OC1 cells and also
      significantly attenuated the cisplatin-induced increase in ROS. In addition,
      metformin inhibited the activation of caspase-3 and levels of poly-ADP-ribose
      polymerase (PARP). Pretreatment with metformin prevented the cisplatin-induced
      elevation in intracellular calcium concentrations. We propose that metformin
      protects against cisplatin-induced ototoxicity by inhibiting the increase in
      intracellular calcium levels, preventing apoptosis, and limiting ROS production.

PMID- 24297264
TI  - Acquired pure red cell aplasia due to treatment with clopidogrel: first case
      report.
AB  - A 62-year-old woman with hypertension, type 2 diabetes mellitus, hyperlipemia and
      coronary heart disease started taking clopidogrel, with no addition of any other
      new drugs. However, with the addition of the drug, the patient was diagnosed as
      having acquired pure red cell aplasia (PRCA), and no any other inducing factors
      were detected from the patient. Furthermore, with the withdrawal of clopidogrel
      from the treatment, the patient recovered from the PRCA and did not recur.
      Therefore, we report PRCA as a rare side effect of clopidogrel for the first
      time. 

PMID- 24297265
TI  - Hemoglobin A1c is a better predictor of prognosis following the non-ST elevation
      acute coronary syndrome than fasting and admission glucose.
AB  - BACKGROUND: Glucometabolic status is an important predictor of prognosis in
      patients with acute myocardial infarction. Both plasma glucose levels and
      glycosylated hemoglobin A1c (HbA1c) were implicated as predictors of prognosis.
      However, previous data yielded conflicting results. We evaluated the prognostic
      role of plasma glucose levels and HbA1c in patients with non-ST elevation acute
      coronary syndrome (NSTEACS). METHODS: A total of 106 consecutive patients with
      NSTEACS (55 with unstable angina and 51 with non-ST elevation myocardial
      infarction) were included. The average age was 66.1 years; 61% were male. HbA1c
      was measured at admission, along with other standard laboratory values. The
      follow-up period lasted for a year. The main combined outcome variable included
      death from cardiovascular causes and rehospitalization due to another acute
      coronary syndrome or due to heart failure. RESULTS: Combined end point occurred
      in 43 (41%) patients. Mean HbA1c value was significantly higher in the group of
      patients who had complications (7.6 +/- 2.6 vs. 5.8 +/- 1.2, p < 0.05). Logistic
      regression identified HbA1c [odds ratio (OR): 1.6] and male sex (OR: 0.25) as the
      only independent predictors of major adverse cardiac events (MACE). A Kaplan
      Meier analysis showed a 2.7 times higher risk of MACE in patients with HbA1c >
      6.5%. CONCLUSIONS: Results from our study indicate that the admission level of
      HbA1c, but not admission or fasting glucose, is a predictor of mortality and
      major adverse events in patients with NSTEACS. These results identify HbA1c to be
      an independent predictor also in patients with NSTEACS, and not only in those
      with ST elevation myocardial infarction as observed before our study.

PMID- 24297267
TI  - The polymicrobial Actinomyces naeslundii and Pseudomonas aeruginosa sepsis in a
      patient with ulcerative colitis 2 months after colonoscopy.
AB  - We describe a case of an abrupt onset of polymicrobial Actinomyces
      naeslundii/Pseudomonas aeruginosa sepsis in a patient with a previously silent
      abdominal actinomycosis, developed 2 months after colonoscopy when the diagnosis
      of a left-sided ulcerative colitis was established. Prolonged high-dose
      ceftriaxone therapy was clinically effective, albeit accompanied by the
      development of a reversible pseudocholelithiasis that persisted for 5 months. 

PMID- 24297266
TI  - [Austrian 3e-recommendations for diagnosis and management of gout 2013].
AB  - BACKGROUND: Gout is the most common inflammatory joint disease in the Western
      world, with increasing prevalence. Like former 3e-initiatives (Experts-Evidence
      Education) dealing with other rheumatological problems, this initiative aimed at
      the development of international recommendations for the diagnosis and management
      of gout and hyperuricemia based on a systematic literature research. METHODS: In
      the participating countries 10 national questions were generated via a Delphi
      process. These questions were collected and out of this pool 10 international
      questions were formulated. Afterwards a systematic literature research was
      performed. On that basis again first national and afterwards international
      recommendations were generated. RESULTS: On the basis of the available literature
      an Austrian expert panel developed 10 recommendations on diagnosis and management
      of gout and hyperuricemia. After publication of the international 3e
      recommendations we hereby present the national Austrian questions and expert
      recommendations for diagnosis and management of gout 2013 followed by a
      comparison of the Austrian and the international recommendations.

PMID- 24297268
TI  - [Society for Clinical Nutrition (AKE)].

PMID- 24297271
TI  - Introduction and overview of this book.

PMID- 24297272
TI  - An overview and practical guide to building Markov state models.

PMID- 24297269
TI  - Almanac 2013: stable coronary artery disease.

PMID- 24297273
TI  - Markov model theory.

PMID- 24297274
TI  - Estimation and validation of Markov models.

PMID- 24297275
TI  - Uncertainty estimation.

PMID- 24297276
TI  - Analysis of Markov models.

PMID- 24297277
TI  - Transition path theory.

PMID- 24297278
TI  - Understanding protein folding using Markov state models.

PMID- 24297279
TI  - Understanding molecular recognition by kinetic network models constructed from
      molecular dynamics simulations.

PMID- 24297280
TI  - Markov state and diffusive stochastic models in electron spin resonance.

PMID- 24297281
TI  - Software for building Markov state models.

PMID- 24297282
TI  - A year of firsts.
AB  - This editorial recounts highlights from 2013 for CBE-Life Sciences Education and
      notes activities on the horizon for 2014.

PMID- 24297283
TI  - PULSE vision & change rubrics.

PMID- 24297284
TI  - Science choreography: a movement-based approach to biology teaching.

PMID- 24297285
TI  - Transdisciplinary training between physics and biology led to the development of
      the hydrodynamics laws.

PMID- 24297286
TI  - "What if students revolt?"--considering student resistance: origins, options, and
      opportunities for investigation.
AB  - Instructors attempting new teaching methods may have concerns that students will
      resist nontraditional teaching methods. The authors provide an overview of
      research characterizing the nature of student resistance and exploring its
      origins. Additionally, they provide potential strategies for avoiding or
      addressing resistance and pose questions about resistance that may be ripe for
      research study.

PMID- 24297287
TI  - Engaging actively with issues in the responsible conduct of science: lessons from
      international efforts are relevant for undergraduate education in the United
      States.
AB  - Numerous studies are demonstrating that engaging undergraduate students in
      original research can improve their achievement in the science, technology,
      engineering, and mathematics (STEM) fields and increase the likelihood that some
      of them will decide to pursue careers in these disciplines. Associated with this
      increased prominence of research in the undergraduate curriculum are greater
      expectations from funders, colleges, and universities that faculty mentors will
      help those students, along with their graduate students and postdoctoral fellows,
      develop an understanding and sense of personal and collective obligation for
      responsible conduct of science (RCS). This Feature describes an ongoing National
      Research Council (NRC) project and a recent report about educating faculty
      members in culturally diverse settings (Middle East/North Africa and Asia) to
      employ active-learning strategies to engage their students and colleagues deeply
      in issues related to RCS. The NRC report describes the first phase of this
      project, which took place in Aqaba and Amman, Jordan, in September 2012 and April
      2013, respectively. Here we highlight the findings from that report and our
      subsequent experience with a similar interactive institute in Kuala Lumpur,
      Malaysia. Our work provides insights and perspectives for faculty members in the
      United States as they engage undergraduate and graduate students, as well as
      postdoctoral fellows, to help them better understand the intricacies of and
      connections among various components of RCS. Further, our experiences can provide
      insights for those who may wish to establish "train-the-trainer" programs at
      their home institutions. 

PMID- 24297288
TI  - Best practices for measuring students' attitudes toward learning science.
AB  - Science educators often characterize the degree to which tests measure different
      facets of college students' learning, such as knowing, applying, and problem
      solving. A casual survey of scholarship of teaching and learning research studies
      reveals that many educators also measure how students' attitudes influence their
      learning. Students' science attitudes refer to their positive or negative
      feelings and predispositions to learn science. Science educators use attitude
      measures, in conjunction with learning measures, to inform the conclusions they
      draw about the efficacy of their instructional interventions. The measurement of
      students' attitudes poses similar but distinct challenges as compared with
      measurement of learning, such as determining validity and reliability of
      instruments and selecting appropriate methods for conducting statistical
      analyses. In this review, we will describe techniques commonly used to quantify
      students' attitudes toward science. We will also discuss best practices for the
      analysis and interpretation of attitude data. 

PMID- 24297289
TI  - The Classroom Observation Protocol for Undergraduate STEM (COPUS): a new
      instrument to characterize university STEM classroom practices.
AB  - Instructors and the teaching practices they employ play a critical role in
      improving student learning in college science, technology, engineering, and
      mathematics (STEM) courses. Consequently, there is increasing interest in
      collecting information on the range and frequency of teaching practices at
      department-wide and institution-wide scales. To help facilitate this process, we
      present a new classroom observation protocol known as the Classroom Observation
      Protocol for Undergraduate STEM or COPUS. This protocol allows STEM faculty,
      after a short 1.5-hour training period, to reliably characterize how faculty and
      students are spending their time in the classroom. We present the protocol,
      discuss how it differs from existing classroom observation protocols, and
      describe the process by which it was developed and validated. We also discuss how
      the observation data can be used to guide individual and institutional change. 

PMID- 24297290
TI  - Development of the biology card sorting task to measure conceptual expertise in
      biology.
AB  - There are widespread aspirations to focus undergraduate biology education on
      teaching students to think conceptually like biologists; however, there is a
      dearth of assessment tools designed to measure progress from novice to expert
      biological conceptual thinking. We present the development of a novel assessment
      tool, the Biology Card Sorting Task, designed to probe how individuals organize
      their conceptual knowledge of biology. While modeled on tasks from cognitive
      psychology, this task is unique in its design to test two hypothesized conceptual
      frameworks for the organization of biological knowledge: 1) a surface feature
      organization focused on organism type and 2) a deep feature organization focused
      on fundamental biological concepts. In this initial investigation of the Biology
      Card Sorting Task, each of six analytical measures showed statistically
      significant differences when used to compare the card sorting results of putative
      biological experts (biology faculty) and novices (non-biology major
      undergraduates). Consistently, biology faculty appeared to sort based on
      hypothesized deep features, while non-biology majors appeared to sort based on
      either surface features or nonhypothesized organizational frameworks. Results
      suggest that this novel task is robust in distinguishing populations of biology
      experts and biology novices and may be an adaptable tool for tracking emerging
      biology conceptual expertise. 

PMID- 24297291
TI  - Understanding clicker discussions: student reasoning and the impact of
      instructional cues.
AB  - Previous research has shown that undergraduate science students learn from peer
      discussions of in-class clicker questions. However, the features that
      characterize such discussions are largely unknown, as are the instructional
      factors that may lead students into productive discussions. To explore these
      questions, we recorded and transcribed 83 discussions among groups of students
      discussing 34 different clicker questions in an upper-level developmental biology
      class. Discussion transcripts were analyzed for features such as making claims,
      questioning, and explaining reasoning. In addition, transcripts were categorized
      by the quality of reasoning students used and for performance features, such as
      percent correct on initial vote, percent correct on revote, and normalized
      learning change. We found that the majority of student discussions included
      exchanges of reasoning that used evidence and that many such exchanges resulted
      in students achieving the correct answer. Students also had discussions in which
      ideas were exchanged, but the correct answer not achieved. Importantly,
      instructor prompts that asked students to use reasoning resulted in significantly
      more discussions containing reasoning connected to evidence than without such
      prompts. Overall, these results suggest that these upper-level biology students
      readily employ reasoning in their discussions and are positively influenced by
      instructor cues. 

PMID- 24297292
TI  - Development of a meiosis concept inventory.
AB  - We have designed, developed, and validated a 17-question Meiosis Concept
      Inventory (Meiosis CI) to diagnose student misconceptions on meiosis, which is a
      fundamental concept in genetics. We targeted large introductory biology and
      genetics courses and used published methodology for question development, which
      included the validation of questions by student interviews (n = 28), in-class
      testing of the questions by students (n = 193), and expert (n = 8) consensus on
      the correct answers. Our item analysis showed that the questions' difficulty and
      discrimination indices were in agreement with published recommended standards and
      discriminated effectively between high- and low-scoring students. We foresee
      other institutions using the Meiosis CI as both a diagnostic tool and an
      instrument to assess teaching effectiveness and student progress, and invite
      instructors to visit http://q4b.biology.ubc.ca for more information.

PMID- 24297293
TI  - The EvoDevoCI: a concept inventory for gauging students' understanding of
      evolutionary developmental biology.
AB  - The American Association for the Advancement of Science 2011 report Vision and
      Change in Undergraduate Biology Education encourages the teaching of
      developmental biology as an important part of teaching evolution. Recently,
      however, we found that biology majors often lack the developmental knowledge
      needed to understand evolutionary developmental biology, or "evo-devo." To assist
      in efforts to improve evo-devo instruction among undergraduate biology majors, we
      designed a concept inventory (CI) for evolutionary developmental biology, the
      EvoDevoCI. The CI measures student understanding of six core evo-devo concepts
      using four scenarios and 11 multiple-choice items, all inspired by authentic
      scientific examples. Distracters were designed to represent the common conceptual
      difficulties students have with each evo-devo concept. The tool was validated by
      experts and administered at four institutions to 1191 students during preliminary
      (n = 652) and final (n = 539) field trials. We used student responses to evaluate
      the readability, difficulty, discriminability, validity, and reliability of the
      EvoDevoCI, which included items ranging in difficulty from 0.22-0.55 and in
      discriminability from 0.19-0.38. Such measures suggest the EvoDevoCI is an
      effective tool for assessing student understanding of evo-devo concepts and the
      prevalence of associated common conceptual difficulties among both novice and
      advanced undergraduate biology majors. 

PMID- 24297294
TI  - A deliberate practice approach to teaching phylogenetic analysis.
AB  - One goal of postsecondary education is to assist students in developing expert
      level understanding. Previous attempts to encourage expert-level understanding of
      phylogenetic analysis in college science classrooms have largely focused on
      isolated, or "one-shot," in-class activities. Using a deliberate practice
      instructional approach, we designed a set of five assignments for a 300-level
      plant systematics course that incrementally introduces the concepts and skills
      used in phylogenetic analysis. In our assignments, students learned the process
      of constructing phylogenetic trees through a series of increasingly difficult
      tasks; thus, skill development served as a framework for building content
      knowledge. We present results from 5 yr of final exam scores, pre- and
      postconcept assessments, and student surveys to assess the impact of our new
      pedagogical materials on student performance related to constructing and
      interpreting phylogenetic trees. Students improved in their ability to interpret
      relationships within trees and improved in several aspects related to between
      tree comparisons and tree construction skills. Student feedback indicated that
      most students believed our approach prepared them to engage in tree construction
      and gave them confidence in their abilities. Overall, our data confirm that
      instructional approaches implementing deliberate practice address student
      misconceptions, improve student experiences, and foster deeper understanding of
      difficult scientific concepts. 

PMID- 24297295
TI  - Engagement and skill development in biology students through analysis of art.
AB  - An activity involving analysis of art in biology courses was designed with the
      goals of piquing undergraduates' curiosity, broadening the ways in which college
      students meaningfully engage with course content and concepts, and developing
      aspects of students' higher-level thinking skills, such as analysis, synthesis,
      and evaluation. To meet these learning outcomes, the activity had three key
      components: preparatory readings, first-hand visual analysis of art during a
      visit to an art museum, and communication of the analysis. Following a
      presentation on the methodology of visual analysis, students worked in small
      groups to examine through the disciplinary lens of biology a selection of
      approximately 12 original artworks related in some manner to love. The groups
      then developed and presented for class members a mini-exhibition of several
      pieces addressing one of two questions: 1) whether portrayals of love in art
      align with the growing understanding of the biology of love or 2) whether the
      bodily experience of love is universal or, alternatively, is culturally
      influenced, as is the experience of depression. Evaluation of quantitative and
      qualitative assessment data revealed that the assignment engaged students,
      supported development of higher-level thinking skills, and prompted meaningful
      engagement with course material.

PMID- 24297296
TI  - Lessons learned from undergraduate students in designing a science-based course
      in bioethics.
AB  - Columbia University offers two innovative undergraduate science-based bioethics
      courses for student majoring in biosciences and pre-health studies. The goals of
      these courses are to introduce future scientists and healthcare professionals to
      the ethical questions they will confront in their professional lives, thus
      enabling them to strategically address these bioethical dilemmas. These courses
      incorporate innovative pedagogical methods, case studies, and class discussions
      to stimulate the students to think creatively about bioethical issues emerging
      from new biotechnologies. At the end of each course, each student is required to
      submit a one-page strategy detailing how he or she would resolve a bioethical
      dilemma. Based on our experience in teaching these courses and on a qualitative
      analysis of the students' reflections, we offer recommendations for creating an
      undergraduate science-based course in bioethics. General recommendations include:
      1) integrating the science of emerging biotechnologies, their ethical
      ramifications, and contemporary bioethical theories into interactive class
      sessions; 2) structuring discussion-based classes to stimulate students to
      consider the impact of their moral intuitions when grappling with bioethical
      issues; and 3) using specific actual and futuristic case studies to highlight
      bioethical issues and to help develop creative problem-solving skills. Such a
      course sparks students' interests in both science and ethics and helps them
      analyze bioethical challenges arising from emerging biotechnologies. 

PMID- 24297297
TI  - What do I want to be with my PhD? The roles of personal values and structural
      dynamics in shaping the career interests of recent biomedical science PhD
      graduates.
AB  - Interest in faculty careers decreases as graduate training progresses; however,
      the process underlying career-interest formation remains poorly defined. To
      better understand this process and whether/how it differs across social identity
      (i.e., race/ethnicity, gender), we conducted focus groups with 38 biomedical
      scientists who received PhDs between 2006 and 2011, including 23 women and 18
      individuals from underrepresented minority (URM) backgrounds. Objective
      performance and quality of advisor relationships were not significantly different
      between scientists with high versus low interest in faculty careers. Career
      interests were fluid and formed in environments that generally lacked structured
      career development. Vicarious learning shaped similar outcome expectations about
      academic careers for all scientists; however, women and URMs recounted
      additional, distinct experiences and expectations. Scientists pursuing faculty
      careers described personal values, which differed by social identity, as their
      primary driver. For scientists with low interest in faculty careers, a
      combination of values, shared across social identity, and structural dynamics of
      the biomedical workforce (e.g., job market, grant funding, postdoc pay, etc.)
      played determinative roles. These findings illuminate the complexity of career
      choice and suggest attracting the best, most diverse academic workforce requires
      institutional leaders and policy makers go beyond developing individual skill,
      attending to individuals' values and promoting institutional and systemic
      reforms. 

PMID- 24297298
TI  - Lanthanide complexes with aromatic o-phosphorylated ligands: synthesis, structure
      elucidation and photophysical properties.
AB  - Lanthanide complexes LnL3 (Ln = Sm, Eu, Tb, Dy, Tm, Yb, Lu) with aromatic o
      phosphorylated ligands (HL(1) and HL(2)) have been synthesized and identified.
      Their molecular structure was proposed on the basis of a new complex approach,
      including DFT calculations, Sparkle/PM3 modelling, EXAFS spectroscopy and
      luminescent probing. The photophysical properties of all of the complexes were
      investigated in detail to obtain a deeper insight into the energy transfer
      processes. 

PMID- 24297299
TI  - National variations in back pain: ecological fallacy or cultural differences?

PMID- 24297300
TI  - AZD8055 induces cell death associated with autophagy and activation of AMPK in
      hepatocellular carcinoma.
AB  - AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in
      several types of cancer cells in vitro and in vivo. However, the effect of
      AZD8055 on hepatocellular carcinoma (HCC) cells has not been studied. We report
      that AZD8055 inhibits cell proliferation and colony formation of Hep3B and Huh7
      cells but does not cause PARP cleavage, or caspase activation, suggesting that
      classical apoptosis is not its main mechanism of cell death. By contrast, AZD8055
      induced cell death was associated with several characteristics of autophagy,
      including an increase in acidic vesicular organelle content, conversion of
      cytosolic LC3-I to membrane-bound LC3-II and elevation of the levels of Atg-5/12,
      BECN1 and LC3-II. Inhibition of autophagy by 3-methyladenine (3-MA) partially
      inhibited AZD8055-induced cell death. Furthermore, AZD8055 caused the activation
      of AMPK and co-treatment with the AMPK inhibitor dorsomorphin also caused a
      partial but significant reduction of AZD8055-induced cell death. In conclusion,
      AZD8055-induced HCC cell death is associated with induction of autophagy and
      activation of AMPK.

PMID- 24297301
TI  - Pregnancy outcomes in women greater than 45 years: a cohort control study in a
      multi-ethnic inner city population.
AB  - OBJECTIVE: To examine the pregnancy outcomes of women >45 years in a multi-ethnic
      population when compared to controls and to reflect on socio-demographic details
      of the older mothers. DESIGN: A retrospective cohort control study over an 8-year
      period in an inner city London hospital with multi-ethnic population. The
      influence of advanced maternal age (>45 years at time of delivery) on fetal and
      maternal outcomes was assessed by comparing these women to controls (aged 20-30
      years) matched for ethnicity, country of origin and parity. RESULTS: Data from 64
      cases and 64 controls were compared. Ninety percent of the index group had
      undergone assisted conception. Mothers >45 years had a fourfold increase in
      cesarean section (35/64 vs 8/64), a threefold increase in blood loss (669.2 vs
      272.4 ml) (both p < 0.001) and were more likely to have preterm birth (12/64 vs
      3/64) (p < 0.05). Only 5 % of the 64 women were born in the United Kingdom, 52 %
      were unemployed and 50 % were not fluent in English. Seventy-five percent of the
      study population were multiparous, 52 % of the pregnancies were unplanned and 90
      % had conceived spontaneously. CONCLUSION: In an inner city immigrant population,
      older mothers >45 years were more likely to have cesarean sections, postpartum
      hemorrhage and premature deliveries. Moreover, social and demographic factors
      suggest that late child bearing is influenced by cultural factors such as
      acceptance of large families and lack of contraception.

PMID- 24297302
TI  - Assessment of oxidative stress markers in recurrent pregnancy loss: a prospective
      study.
AB  - OBJECTIVE: To determine the levels of oxidative stress markers in recurrent
      pregnancy loss using a novel automated method. MATERIALS AND METHODS: 30 pregnant
      women in their first trimester with a history of recurrent pregnancy loss (RPL)
      and 30 healthy pregnant women were enrolled in this prospective controlled study.
      Total antioxidant capacity (TAC), total oxidant level (TOL) and oxidative stress
      index (OSI) in maternal serum were measured using the more recently designated
      Erel method. RESULTS: We observed statistically significant increased TOL and OSI
      levels in patient group (p = 0.032, p = 0.007, respectively). We also
      demonstrated statistically significant decreased TAC in pregnant women who had a
      history of RPL (p = 0.013). CONCLUSION: Our results support the concept that
      oxidative stress plays a central role in the etiopathogenesis of RPL. Further
      studies to evaluate the predictive role of TAC, TOL, OSI levels using Erel method
      are needed.

PMID- 24297303
TI  - Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients
      undergoing liver transplantation.
AB  - BACKGROUND: It is not clear whether prophylactic antiviral therapy is indicated
      to improve patient and graft survival in patients undergoing liver
      transplantation for chronic decompensated hepatitis C virus (HCV) infection.
      OBJECTIVES: To compare the benefits and harms of different prophylactic antiviral
      therapies for patients undergoing liver transplantation for chronic HCV
      infection. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation
      Index Expanded to February 2013. SELECTION CRITERIA: Only randomised clinical
      trials irrespective of language, blinding, or publication status and comparing
      various prophylactic antiviral therapies (alone or in combination) in the
      prophylactic treatment of patients undergoing liver transplantation for chronic
      HCV infection. DATA COLLECTION AND ANALYSIS: Two authors collected the data
      independently. We calculated the risk ratio (RR) or mean difference (MD) or
      hazard ratio (HR) with 95% confidence intervals (CI) using the fixed-effect and
      the random-effects models based on available case analysis. MAIN RESULTS: A total
      of 501 liver transplant recipients undergoing liver transplantation for chronic
      HCV infection were randomised in 12 trials to various experimental interventions
      and control interventions. The proportion of genotype I varied between 49% and
      100% in the seven trials that reported the genotype. Only one or two trials were
      included under each comparison. All the trials were of high risk of bias. Ten
      trials including 441 liver transplant recipients provided data for this
      review.There were no significant differences in the 90-day mortality (1 trial; 81
      participants; 5/35 (adjusted proportion: 14.2%) in interferon group versus 5/46
      (10.9%) in control group; RR 1.31; 95% CI 0.41 to 4.19); mortality at maximal
      follow-up (2 trials; 105 participants; 7/47 (adjusted proportion: 14.8%) in
      interferon group versus 10/58 (17.2%) in control group; RR 0.86; 95% CI 0.36 to
      2.08); long-term mortality (1 trial; 81 participants; HR 0.45; 95% CI 0.13 to
      1.56); mortality at maximal follow-up (1 trial; 54 participants; 1/26 (3.9%) in
      pegylated interferon group versus 2/28 (7.1%) in control group; RR 0.54; 95% CI
      0.05 to 5.59); 90-day mortality (1 trial; 115 participants; 5/55 (9.1%) in
      pegylated interferon plus ribavirin group versus 3/60 (5.0%) in control group; RR
      1.82; 95% 0.46 to 7.25); 90-day mortality (3 trials; 53 participants; 3/37
      (adjusted proportion: 4.3%) in HCV antibody group versus 1/16 (6.3%) in placebo
      group; RR 0.69; 95% CI 0.15 to 3.11); or 90-day mortality (2 trials; 31
      participants; 2/14 (adjusted proportion: 16.2%) in HCV antibody high-dose group
      versus 1/17 (5.9%) in HCV antibody low-dose group; RR 2.75; 95% CI; 0.30 to
      25.35). There were no significant differences in the retransplantation at maximal
      follow-up (2 trials; 105 participants; 2/47 (adjusted proportion: 4.0%) in
      interferon group versus 2/58 (3.4%) in control group; RR 1.17; 95% CI 0.22 to
      6.2); 90-day retransplantation (1 trial; 18 participants; 1/12 (8.3%) in HCV
      antibody group versus 0/6 (0%) in control group; RR 1.71; 95% CI 0.09 to 32.93);
      or 90-day retransplantation (1 trial; 12 participants; 1/6 (17.7%) in HCV
      antibody high-dose group versus 0/6 (0%) in HCV antibody low-dose group; RR 3.00;
      95% CI 0.15 to 61.74). There were no significant differences in serious adverse
      events, graft rejection, worsening of fibrosis, or HCV recurrence between
      intervention and control groups in any of the comparisons that reported these
      outcomes. None of the trials reported quality of life, liver decompensation,
      intensive therapy unit stay, or hospital stay. Life-threatening adverse events
      were not reported in either group in any of the comparisons. AUTHORS'
      CONCLUSIONS: There is currently no evidence to recommend prophylactic antiviral
      treatment to prevent recurrence of HCV infection either in primary liver
      transplantation or retransplantation. Further randomised clinical trials with
      adequate trial methodology and adequate duration of follow-up are necessary.

PMID- 24297304
TI  - An efficient early phase 2 procedure to screen medications for efficacy in
      smoking cessation.
AB  - RATIONALE: Initial screening of new medications for potential efficacy (i.e.,
      Food and Drug Administration (FDA) early phase 2), such as in aiding smoking
      cessation, should be efficient in identifying which drugs do, or do not, warrant
      more extensive (and expensive) clinical testing. OBJECTIVES: This focused review
      outlines our research on development, evaluation, and validation of an efficient
      crossover procedure for sensitivity in detecting medication efficacy for smoking
      cessation. First-line FDA-approved medications of nicotine patch, varenicline,
      and bupropion were tested as model drugs, in three separate placebo-controlled
      studies. We also tested specificity of our procedure in identifying a drug that
      lacks efficacy, using modafinil. RESULTS: This crossover procedure showed
      sensitivity (increased days of abstinence) during week-long "practice" quit
      attempts with each of the active cessation medications (positive controls) versus
      placebo, but not with modafinil (negative control) versus placebo, as
      hypothesized. Sensitivity to medication efficacy signal was observed only in
      smokers high in intrinsic quit motivation (i.e., already preparing to quit soon)
      and not smokers low in intrinsic quit motivation, even if monetarily reinforced
      for abstinence (i.e., given extrinsic motivation). CONCLUSIONS: A crossover
      procedure requiring less time and fewer subjects than formal trials may provide
      an efficient strategy for a go/no-go decision whether to advance to subsequent
      phase 2 randomized clinical trials with a novel drug. Future research is needed
      to replicate our results and evaluate this procedure with novel compounds,
      identify factors that may limit its utility, and evaluate its applicability to
      testing efficacy of compounds for treating other forms of addiction.

PMID- 24297306
TI  - Commercial bumblebee hives to assess an anthropogenic environment for pollinator
      support: a case study in the region of Ghent (Belgium).
AB  - Anthropogenic changes of the environment influence the distribution and abundance
      of pollinators such as bumblebees and have been proposed as one of the main
      causes in their worldwide decline. In order to evaluate the impact of expanding
      anthropogenic landscapes on supporting pollinator potential, reliable tools are
      needed. Bombus terrestris is one of the most abundant bumblebee species in
      Europe, and these bumblebees are known as generalist pollinators of not only wild
      flowers in nature but also of crops in agriculture. For more than two decades,
      these bumblebees have been commercially mass reared for biological pollination in
      greenhouses. In this project, we placed commercial hives of the bumblebee B.
      terrestris containing one queen and 40 workers, in three different locations in
      the region of Ghent (Belgium), and the performance of these hives was followed
      during a 4-week period in spring 2012. In parallel, we determined the floral
      richness and diversity index in the chosen study sites. The sites consisted of a
      rich urban environment with patchy green areas opposed to an urban environment
      with poor landscape metrics; a third rural study site showed average positive
      landscape metrics. The results demonstrated that the hive biomass and numbers of
      workers increased significantly in the rich compared to the poor environment,
      providing a mechanism to discriminate between study sites. In addition, the
      bumblebee-collected pollen showed that the flowering plants Salix spp. and
      Rosaceae/Prunus spp. are dominant food sources in all anthropogenic environments
      during early spring. Finally, the results are discussed in relation to the
      optimization of the experimental setup and to the use of commercial bumblebee
      hives in assessing local pollinator support within any given environment. 

PMID- 24297305
TI  - Chronic curcumin treatment normalizes depression-like behaviors in mice with
      mononeuropathy: involvement of supraspinal serotonergic system and GABAA
      receptor.
AB  - RATIONALE: Comorbid depression is commonly observed in individuals who suffer
      from neuropathic pain, which necessitates improved treatment. Curcumin, a
      phenolic compound derived from Curcuma longa, possesses both antinociceptive and
      antidepressant-like activities in animal studies, suggesting its possible
      usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of
      curcumin on depressive-like behaviors in mice with mononeuropathy, and explored
      the mechanism(s). METHODS: Chronic constriction injury (CCI) was produced by
      loosely ligating the sciatic nerves in mice. The nociceptive behaviors were
      examined using Hargreaves test, and the depressive-like behaviors were determined
      by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI
      injury, the neuropathic mice developed nociceptive and depressive-like behaviors,
      as shown by thermal hyperalgesia in Hargreaves test and protracted immobility
      time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45
      mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive
      and depressive-like behaviors, which was abolished by chemical depletion of brain
      serotonin rather than noradrenaline. The paralleled antinociceptive and
      antidepressant-like actions of curcumin seem to be pharmacologically segregated,
      since intrathecal and intracerebroventricular injection of methysergide, a
      nonselective 5-HT receptor antagonist, separately counteracted the two actions of
      curcumin. Further, this antidepression was abrogated by repeated co-treatment
      with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co
      treatment with GABAA receptor antagonist bicuculline. CONCLUSION: Curcumin can
      normalize the depressive-like behaviors of neuropathic mice, which may be
      independent of the concurrent analgesic action and possibly mediated via the
      supraspinal serotonergic system and downstream GABAA receptor.

PMID- 24297307
TI  - Coupling of solvent-based de-emulsification dispersive liquid-liquid
      microextraction with high performance liquid chromatography for simultaneous
      simple and rapid trace monitoring of 2,4-dichlorophenoxyacetic acid and 2-methyl
      4-chlorophenoxyacetic acid.
AB  - A simple, rapid, and efficient sample pretreatment technique, based on solvent
      based de-emulsification dispersive liquid-liquid microextraction (SD-DLLME),
      followed by high performance liquid chromatography (HPLC) has been developed for
      simultaneous preconcentration and trace detection of 2,4-dichlorophenoxyacetic
      acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in water and urine
      samples. Some parameters such as acidity of solution, the amount of salt, type,
      and volume of extraction solvents, type of disperser/de-emulsifier solvent, and
      its volume were investigated and optimized. Under optimum extraction conditions,
      the limits of detections (LODs) of this method for MCPA and 2,4-D were 0.2 and
      0.6 MUg L(-1) (based on 3S(b)/m) in water and 0.4 and 1.6 MUg L(-1) in urine,
      respectively. Furthermore, dynamic linear range of this method for MCPA and 2,4-D
      was 1-300 and 2-400 MUg L(-1), repectively. Finally, the applicability of the
      proposed method was evaluated by extraction and determination of the herbicides
      in urine and different water samples.

PMID- 24297308
TI  - MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal
      squamous cell carcinoma.
AB  - MicroRNAs were reported to be involved in the modulation of tumor development.
      The aim of our study was to investigate the effect of miR-205 on proliferation
      and apoptosis of laryngeal squamous cell carcinoma (LSCC) and seek associations
      between miR-205 and Bcl-2 using in vitro and in vivo methods. Real-time qPCR was
      used to analyze the expression of miR-205 in LSCC samples and Hep-2 cell line.
      Apoptosis, cell cycle, and proliferation (MTT) assays were performed to test the
      apoptosis and proliferation of LSCC cells after miR-205 transfection. Bcl-2
      expression in cells was assessed with Western blotting. The tumorigenicity of
      LSCC cells was evaluated in nude mice model. MiR-205 was significantly down
      regulated in LSCC tissues compared to adjacent normal tissues. Lower expression
      of miR-205 was indicated to be statistically related with advanced clinical stage
      and T3-4 grades. We found that restoration of miR-205 down-regulated the
      proliferative markers of dihydrofolate reductase and proliferating cell nuclear
      antigen and apoptotic regulator of Bcl-2. The findings in vitro and in vivo
      showed miR-205 could suppress cell proliferation and induce cell apoptosis. In
      addition, Bcl-2 was identified as one of the direct targets of miR-205 in LSCC
      cells. These results suggest that miR-205 may play as a tumor suppressor in LSCC,
      probably by targeting Bcl-2 and serve as a potential target for therapeutic
      intervention. 

PMID- 24297309
TI  - Diagnostic and prognostic significance of peroxiredoxin 1 expression in human
      hepatocellular carcinoma.
AB  - Peroxiredoxin 1 (Prdx1) is a member of the peroxiredoxin family of antioxidant
      enzymes and implicated in cell differentiation, proliferation, and apoptosis. The
      aim of the present study was to determine the expression and diagnostic and
      prognostic significance of Prdx1 in human hepatocellular carcinoma (HCC). Prdx1
      expression was examined in 76 HCC patients and 20 healthy volunteers. The
      relationships between Prdx1 expression and clinicopathological features were
      analyzed. Receiver operating characteristics analysis was used to calculate the
      diagnostic accuracy of serum Prdx1, serum alpha-fetoprotein (AFP), and their
      combination. The prognostic impact of Prdx1 on overall survival (OS) and disease
      free survival (DFS) of HCC patients was investigated. Prdx1-positive rate was
      significantly (p < 0.05) higher in HCC (77.1 %) than in adjacent non-tumorous
      liver tissues (18.4 %). Prdx1 immunoreactivity was positively correlated with
      tumor vascular endothelial growth factor expression and microvessel density.
      Prdx1 expression was significantly associated with tumor size, microvascular
      invasion, Edmondson grade, tumor capsula status, serum AFP, and tumor-node
      metastasis stage. The combination of serum Prdx1 and AFP had a markedly higher
      area under the curve than serum Prdx1 alone. Positive Prdx1 expression was
      associated with unfavorable OS (p = 0.004) and DFS (p = 0.001). Multivariate
      analysis revealed intra-tumoral Prdx1 staining as an independent poor prognostic
      marker for OS (p = 0.006) and DFS (p = 0.002). Taken together, our data suggest
      that increased Prdx1 expression is associated with tumor angiogenesis and
      progression in HCC and serves as a promising biomarker for detection and
      prognosis of this malignancy.

PMID- 24297310
TI  - Analysis of a chitinase from EpapGV, a fast killing betabaculovirus.
AB  - The main function of baculoviral chitinase protein (V-CHIA) is to promote the
      final liquefaction of infected host larvae, facilitating the dispersion of
      occlusion bodies (OBs) in the environment. In this study, a v-chiA from Epinotia
      aporema Granulovirus (EpapGV) was identified and characterized. The 1,713 base
      pairs long open reading frame encodes a protein of 570 amino acids with a
      predicted molecular weight of 63 kDa. EpapGV V-CHIA sequence alignment resulted
      62 % identical to Pieris rapae GV and Blastp search revealed a high conservation
      among all baculovirus chitinases. Amino acid sequence analysis indicated that the
      C-terminal KDEL present in most alphabaculovirus chitinases is absent in EpapGV V
      CHIA, as well as in the rest of the betabaculoviruses. Phylogenetic analysis was
      performed with bacterial, lepidopteran, and baculoviral chitinase sequences
      available in databases. Using an AcMNPV bacmid (bApGOZA) a recombinant Ac
      chiAEpapGV was obtained in order to overexpress EpapGV V-CHIA in cell culture.
      The presence of chitinase was detected in purified AcMNPV-chiAEpapGV OBs.
      Peritrophic membranes of Anticarsia gemmatalis larvae fed with recombinant OBs
      showed an altered structure. The results presented in this study show that EpapGV
      chitinase overexpression in recombinant baculovirus can cause association of this
      protein with OBs, and suggest that this could be used to evaluate the protein
      role in early stages of baculoviral infections.

PMID- 24297311
TI  - Evidences for the existence of intermolecular disulfide-bonded oligomers in the
      H3 hemagglutinins expressed in insect cells.
AB  - The hemagglutinin (HA) protein as the predominant antigen, executes receptor
      binding and membrane fusion, which critically influence the virological
      characteristics of influenza viruses. The literature contained scattered data
      showing reduction-sensitive HA oligomers when HA proteins were analyzed under non
      reducing conditions. However, whether the reduction-sensitive HA oligomers are
      inter-monomer disulfide-bonded has not been studied. Here, we showed: (1) the
      detection of beta-mercaptoethanol-sensitive H3 HA oligomers was not affected by
      the treatment of cells with iodoacetamide prior to cell solubilization; (2) H3 HA
      oligomers were present on cell surfaces; (3) H3 HA oligomers had higher density
      than monomers; and (4) mutation of all the five C-terminal cysteines completely
      abolished the formation of H3 HA oligomers. Furthermore, mutant HAs with
      mutations of TM cysteines, CT cysteines or all five cysteines had decreased
      thermal stability but increased fusion activity in comparison with wildtype HA.
      In conclusion, this study has presented enough evidence for the existence of
      inter-monomer S-S H3 HA oligomers formed by five C-terminal cysteines, and
      suggested that all five C-terminal cysteines exerted opposite effects on HA
      thermal stability and fusion activity. 

PMID- 24297312
TI  - Viscosity and drag force involved in organelle transport: investigation of the
      fluctuation dissipation theorem.
AB  - We observed the motion of an organelle transported by motor proteins in cells
      using fluorescence microscopy. Particularly, among organelles, the mitochondria
      in PC12 cells were studied. A mitochondrion was dragged at a constant speed for
      several seconds without pausing. We investigated the fluctuation dissipation
      theorem for this constant drag motion by comparing it with the motion of Brownian
      beads that were incorporated into the cells by an electroporation method. We
      estimated the viscosity value inside cells from the diffusion coefficients of the
      beads. Then the viscosity value obtained by using the beads was found to be
      slightly lower than that obtained from the diffusion coefficient for the
      organelle motion via the Einstein relation. This discrepancy indicates the
      violation of the Einstein relation for the organelle motion. 

PMID- 24297313
TI  - Improvement of intestinal microflora balance by polysaccharide from Physalis
      alkekengi var. francheti.
AB  - A water-soluble polysaccharide fraction (PPSB) was fractionated from Physalis
      alkekengi var. francheti and purified using DEAE-52 Cellulose and Sephadex G-200
      chromatography. The physicochemical properties of PPSB and its molecular
      activities involved in the improvement of intestinal microflora balance were
      evaluated. PPSB (12.5-25.0 mg/ml) was shown to promote the growth of
      Lactobacillus delbrueckii and to inhibit the growth of Escherichia coli.
      Denaturing gradient gel electrophoresis analysis identified Bacteroides,
      Lactobacillus, Helicobacter, Prevotella, Enterococcus, Odoribacter, Alistipes and
      Akkermansia as dominant organisms in the intestinal tract of mice. PPSB exhibited
      stimulatory effects on the growth of probiotic bacteria but inhibitory effects on
      the growth of pathogenic bacteria in vitro. The number of species and quantity of
      the Lactobacillus genus increased significantly with increasing concentrations of
      PPSB in vivo. Experimental results of this study suggest that PPSB may improve
      intestinal microflora imbalances and therefore has strong potential as a natural
      agent for restoring the intestinal microflora balance.

PMID- 24297314
TI  - A Simple Protocol for the Generation of Cardiomyocytes from Human Pluripotent
      Stem Cells.
AB  - Efficient generation of cardiomyocytes from pluripotent stem cells (PSCs) for
      multiple downstream applications such as regenerative medicine, disease modeling,
      and drug screening remains a challenge. Cardiomyogenesis may be regulated in
      vitro by a controlled differentiation process, which involves various signaling
      molecules and extracellular environment. Here, we describe a simple method to
      efficiently generate cardiomyocytes from human embryonic stem cells and human
      induced pluripotent stem cells. 

PMID- 24297315
TI  - Use of Multicolor Flow Cytometry for Isolation of Specific Cell Populations
      Deriving from Differentiated Human Embryonic Stem Cells.
AB  - Flow Cytometry-Sorting (FCM-Sorting) is a technique commonly used to identify and
      isolate specific types of cells from a heterogeneous population of live cells.
      Here we describe a multicolor flow cytometry technique that uses five distinct
      cell surface antigens to isolate four live populations with different surface
      antigen profiles. These profiles were used to help distinguishing between neural
      and nonneural (the lens) ectoderm derivatives within a highly heterogenous
      population of differentiating human embryonic stem cells (hESC). 

PMID- 24297316
TI  - Generation of Megakaryocytes and Platelets from Human Pluripotent Stem Cells.
AB  - Human pluripotent stem cells (hPSC) have the potential to produce any tissue type
      in the body and thus represent a source of cells for regenerative medicine. Here
      we have shown that human platelets can be produced from embryonic or induced
      pluripotent stem cells in a defined culture system. We describe a serum- and
      feeder-free culture system that enabled the generation of megakaryocyte (Mk)
      progenitors and functional platelets from hPSCs. After 13 days the differentiated
      population included precursor cells that formed colonies containing
      differentiated Mks, and after 20 days these Mks were able to fragment into
      platelet-like particles that were functional. This protocol represents an
      important step towards the generation of human platelets for therapeutic use. 

PMID- 24297317
TI  - Analysis and meta-analysis of transcriptional profiling in human epidermis.
AB  - Because of its accessibility, skin has been among the first organs analyzed using
      DNA microarrays; psoriasis, melanomas, carcinomas, chronic wounds, and responses
      of epidermal keratinocytes in culture have been intensely investigated. Skin has
      everything: stem cells, differentiation, signaling, inflammation, hereditary
      diseases, etc. Here we provide step-by-step instructions for bioinformatics
      analysis of transcriptional profiling of skin. We also present methods for meta
      analysis of transcription profiles from multiple contributors, available in
      public data repositories. Specifically, we describe the use of GCOS and
      RMAExpress programs for initial normalization and selection of differentially
      expressed genes and RankProd for meta-analysis of multiple related studies. We
      also describe DAVID and Lists2Networks programs for annotation of genes, and for
      statistically relevant identification of over- and underrepresented functional
      and biological categories in identified gene sets, as well as oPOSSUM for
      analysis of transcription factor binding sites in the promoter regions of gene
      sets. This work can serve as a primer for researchers embarking on skinomics, the
      comprehensive analysis of transcriptional changes in skin.

PMID- 24297318
TI  - A randomized controlled trial to evaluate the effectiveness of a cognitive
      behavioural group approach to improve patient adherence to peritoneal dialysis
      fluid restrictions: a pilot study.
AB  - BACKGROUND: Peritoneal dialysis (PD) requires patients to take an active role in
      their adherence to fluid restrictions. Although fluid non-adherence had been
      identified among this patient group, no specific interventions have been
      researched or published with in the PD population. The current study sought to
      investigate whether an applied cognitive behavioural therapy (CBT-based
      intervention) used among haemodialysis patients would improve fluid adherence
      among PD patients; utilizing clinical indicators used in practice. METHODS:
      Fifteen PD patients identified as fluid non-adherent were randomly assigned to an
      intervention group (IG) or a deferred-entry control group (CG). The study ran for
      a total of 21 weeks, with five data collection points; at baseline, post
      intervention and at three follow-up points; providing a RCT phase and a combined
      longitudinal analysis phase. The content of the group intervention encompassed
      educational, cognitive and behavioural components, aimed to assist patients' self
      management of fluid. RESULTS: No significant differences in weight (kg) reduction
      were found in either phase and undesirable changes in blood pressure (BP) were
      observed. However, in the longitudinal phase, a statistically significant
      difference in oedematous status was observed at 6-week follow-up; which may be
      indicative of fluid adherence. Positive and significant differences were observed
      in the desired direction for measures of psychological well-being, quality of
      life and health beliefs; areas correlated with enhanced fluid adherence in other
      research. CONCLUSIONS: This study reveals encouraging and significant changes in
      predictors of fluid adherence. Although there were no significant changes in
      weight as a crude clinical measure of fluid intake, significant reductions in
      oedematous status were observed as a consequence of this CBT-based group
      intervention.

PMID- 24297319
TI  - Possible diagnostic role of antibodies to Crohn's disease peptide (ACP): results
      of a multicenter study in a Japanese cohort.
AB  - BACKGROUND: Various noninvasive tests have been studied to screen for patients
      with Crohn's disease (CD), and were found to have limited accuracy and
      sensitivity, particularly in Asian populations. The aim of our study was to
      explore the possible diagnostic utility of antibodies to the CD peptide (ACP) in
      patients with CD. METHODS: In a multicenter study using enzyme-linked
      immunosorbent assay, serum ACP levels were determined in 196 patients with CD,
      210 with ulcerative colitis, 98 with other intestinal diseases, 132 with other
      inflammatory diseases, and 183 healthy controls. and then examined for
      correlation to clinical variables. The diagnostic utility of ACP was evaluated by
      receiver operating characteristics analysis and compared with anti-Saccharomyces
      cerevisiae antibodies (ASCA). RESULTS: ACP levels were significantly elevated in
      the CD patients, but not in the other groups that included UC, other intestinal
      diseases, other inflammatory diseases and the healthy controls. Among these other
      groups, ACP levels were not significantly different. In the CD patients, ACP had
      a higher sensitivity and specificity (63.3 and 91.0 %, respectively) than ASCA
      (47.4 and 90.4 %). ACP levels were negatively associated with disease duration,
      but not with CDAI, disease location, or medical treatment. CONCLUSIONS: ACP, a
      newly proposed serologic marker, was significantly associated with CD and was
      highly diagnostic. Further investigation is needed across multiple populations of
      patients and ethnic groups, and more importantly, in prospective studies.

PMID- 24297320
TI  - Novel EXT1 mutation identified in a pedigree with hereditary multiple exostoses.
AB  - Hereditary multiple exostoses (HME) is an autosomal dominant bone disorder
      characterized by the presence of multiple benign cartilage-capped tumors. EXT1
      located on chromosome 8q23-q24 and EXT2 located on 11p11-p12 are the main disease
      causing genes which are responsible for ~90% of HME cases. Mutations of EXT1 or
      EXT2 result in insufficient heparan sulfate biosynthesis, which facilitates
      chondrocyte proliferation, boosts abnormal bone growth of neighboring regions,
      causes multiple exostoses, and ultimately leads to possible malignant
      transformation. A family who displayed typical features of HME was enrolled in
      the present study. Mutation screening by Sanger sequencing identified a novel
      heterozygous nonsense mutation c.1902C>A (p.Tyr634X) in the EXT1 gene exclusively
      in all 3 patients, which is located in the glycosyltransferase domain and results
      in the truncation of 112 amino acids at the C-terminus of the EXT1 protein. Thus,
      the present study identified a novel disease-causing EXT1 mutation in a pedigree
      with HME, which provides additional evidence for developing quick and accurate
      genetic tools for HME diagnosis.

PMID- 24297321
TI  - Immunological characteristics of human umbilical cord mesenchymal stem cells and
      the therapeutic effects of their transplantion on hyperglycemia in diabetic rats.
AB  - Islet transplantation involves the transplantation of pancreatic islets from the
      pancreas of a donor to another individual. It has proven to be an effective
      method for the treatment of type 1 diabetes. However, islet transplantation is
      hampered by immune rejection, as well as the shortage of donor islets. Human
      umbilical cord Wharton's jelly-derived mesenchymal stem cells (HUMSCs) are an
      ideal cell source for use in transplantation due to their biological
      characteristics and their use does not provoke any ethical issues. In this study,
      we investigated the immunological characteristics of HUMSCs and their effects on
      lymphocyte proliferation and the secretion of interferon (IFN)-gamma, and
      explored whether direct cell-to-cell interactions and soluble factors, such as
      IFN-gamma were important for balancing HUMSC-mediated immune regulation. We
      transplanted HUMSCs into diabetic rats to investigate whether these cells can
      colonize in vivo and differentiate into pancreatic beta-cells, and whether the
      hyperglycemia of diabetic rats can be improved by transplantation. Our results
      revealed that HUMSCs did not stimulate the proliferation of lymphocytes and did
      not induce allogeneic or xenogeneic immune cell responses. qRT-PCR demonstrated
      that the HUMSCs produced an immunosuppressive isoform of human leukocyte antigen
      (HLA-I) and did not express HLA-DR. Flow cytometry revealed that the HUMSCs did
      not express immune response-related surface antigens such as, CD40, CD40L, CD80
      and CD86. IFN-gamma secretion by human peripheral blood lymphocytes was reduced
      when the cells were co-cultured with HUMSCs. These results suggest that HUMSCs
      are tolerated by the host in an allogeneic transplant. We transplanted HUMSCs
      into diabetic rats, and the cells survived in the liver and pancreas.
      Hyperglycemia of the diabetic rats was improved and the destruction of pancreatic
      cells was partly repaired by HUMSC transplantation. Hyperglycemic improvement may
      be related to the immunomodulatory effects of HUMSCs. However, the exact
      mechanisms involved remain to be further clarified.

PMID- 24297322
TI  - Characterizing elemental, equivalent black, and refractory black carbon aerosol
      particles: a review of techniques, their limitations and uncertainties.
AB  - Elemental-, equivalent black- and refractory black-carbon are terms that have
      been defined in order to dissect the more general term, black carbon, into its
      component parts related to its specific chemical and optical properties and its
      impact on climate and health. Recent publications have attempted to clarify the
      meaning of these terms with respect to their environmental impact, particularly
      on climate. Here, we focus on the measurement aspects, reviewing the most
      commonly implemented techniques for the direct and indirect derivation of black
      carbon properties, their strengths, limitations, and uncertainties, and provide a
      non-exhaustive bibliography where the reader can find more detailed information.
      This review paper is designed as a guide for those wishing to learn about the
      current state of black carbon measurement instrumentation, how calibration is
      carried out, when one instrument may have the advantage over another, and where
      new techniques are needed to fill important knowledge gaps. 

PMID- 24297323
TI  - Ceftriaxone increases glutamate uptake and reduces striatal tyrosine hydroxylase
      loss in 6-OHDA Parkinson's model.
AB  - Excess glutamatergic neurotransmission may contribute to excitotoxic loss of
      nigrostriatal neurons in Parkinson's disease (PD). Here, we determined if
      increasing glutamate uptake could reduce the extent of tyrosine hydroxylase (TH)
      loss in PD progression. The beta-lactam antibiotic, ceftriaxone, increases the
      expression of glutamate transporter 1 (GLT-1), a glutamate transporter that plays
      a major role in glutamate clearance in central nervous system and may attenuate
      adverse behavioral or neurobiological function in other neurodegenerative disease
      models. In association with >80% TH loss, we observed a significant decrease in
      glutamate uptake in the established 6-hydroxydopamine (6-OHDA) PD model.
      Ceftriaxone (200 mg/kg, i.p.) increased striatal glutamate uptake with >5
      consecutive days of injection in nonlesioned rats and lasted out to 14 days
      postinjection, a time beyond that required for 6-OHDA to produce >70% TH loss (~9
      days). When ceftriaxone was given at the time of 6-OHDA, TH loss was ~57%
      compared to ~85% in temporally matched vehicle-injected controls and amphetamine
      induced rotation was reduced about 2-fold. This attenuation of TH loss was
      associated with increased glutamate uptake, increased GLT-1 expression, and
      reduced Serine 19 TH phosphorylation, a calcium-dependent target specific for
      nigrostriatal neurons. These results reveal that glutamate uptake can be targeted
      in a PD model, decrease the rate of TH loss in a calcium-dependent manner, and
      attenuate locomotor behavior associated with 6-OHDA lesion. Given that detection
      of reliable PD markers will eventually be employed in susceptible populations,
      our results give credence to the possibility that increasing glutamate uptake may
      prolong the time period before locomotor impairment occurs.

PMID- 24297324
TI  - Effect of lung fibrosis on glycogen content in different extrapulmonary tissues.
AB  - PURPOSE: Patients with pulmonary fibrosis often exhibit reduced lung function and
      diminished health-related quality of life. Studies have shown that paraquat
      induced, extrapulmonary, acute lung injury affects the metabolic profile of
      glycogen content in different tissues. The purpose of the present study was to
      investigate whether the process of pulmonary fibrosis induced by continuous
      exposure to the toxic herbicide paraquat or by a local insult from bleomycin
      affects the glycogen content in tissues. METHODS: In the paraquat experiment,
      Wistar rats (n = 5 per group) received either saline (controls) or an
      intraperitoneal injection of a paraquat solution (7.0 mg/kg; experimental group)
      once a week for 4 weeks. In the bleomycin experiment, Balb/c mice (n = 5 per
      group) received either saline (controls) or 6.25 U/kg of bleomycin through
      intratracheal instillation in single dose (experimental group). Glycogen content
      in different tissues (mg/g tissue) was measured using the anthrone reagent. The
      lungs submitted to histopathological and quantitative analyses of fibrosis.
      RESULTS: Paraquat-induced fibrosis led to lower glycogen content in the
      gastrocnemius muscle (2.7 +/- 0.1 vs. 3.4 +/- 0.1; 79 %) compared with the
      controls, whereas no changes in glycogen content were found in the diaphragm or
      heart. Bleomycin-induced fibrosis led to lower glycogen content in the diaphragm
      (0.43 +/- 0.02 vs. 0.79 +/- 0.09, 54 %), gastrocnemius muscle (0.62 +/- 0.11 vs.
      1.18 +/- 0.06, 52 %), and heart (0.68 +/- 0.11 vs. 1.39 +/- 0.1, 49 %) compared
      with the controls (p < 0.05). Moreover, the area of fibrous connective tissue
      (MUm(2)) in the lungs was significantly increased in paraquat-induced fibrosis
      (3,463 +/- 377 vs. 565 +/- 89) and bleomycin-induced fibrosis (3,707 +/- 433.9
      vs. 179 +/- 51.28) compared with the controls. CONCLUSIONS: The findings suggest
      that the effects of fibrogenesis in the lungs are not limited to local
      alterations but also lead to a reduction in glycogen content in the heart and
      other muscles. This reduction could partially explain the impaired muscle
      performance found in patients with pulmonary fibrosis.

PMID- 24297325
TI  - Airway protective mechanisms.
AB  - Cough and swallow are highly coordinated reflex behaviors whose common purpose is
      to protect the airway. The pharynx is the common tube for air and food/liquid
      movement from the mouth into the thorax, has been largely overlooked, and is
      potentially seen as just a passive space. The thyropharyngeus muscle responds to
      cough inducing stimuli to prepare a transient holding area for material that has
      been removed from the subglottic airway. The cricopharyngeus muscle participates
      with the larynx to ensure regulation of pressure when a bolus/air is moving from
      the upper airway through to the thorax (i.e., inspiration or swallow) or the
      reverse (i.e., expiration reflex or vomiting). These vital mechanisms have not
      been evaluated in clinical conditions but could be impaired in many
      neurodegenerative diseases, leading to aspiration pneumonia. These newly
      described airway protective mechanisms need further study, especially in healthy
      and pathologic human populations. 

PMID- 24297326
TI  - Fermentation of soybean oil deodorizer distillate with Candida tropicalis to
      concentrate phytosterols and to produce sterols-rich yeast cells.
AB  - Phytosterols have been recovered from the deodorizer distillate produced in the
      final deodorization step of vegetable oil refining by various processes. The
      deodorizer distillate contains mainly free fatty acids (FFAs), phytosterols, and
      tocopherols. The presence of FFAs hinders recovery of phytosterols. In this
      study, fermentation of soybean oil deodorizer distillate (SODD) with Candida
      tropicalis 1253 was carried out. FFAs were utilized as carbon source and
      converted into cellular components as the yeast cells grew. Phytosterols
      concentration in SODD increased from 15.2 to 28.43 % after fermentation. No
      significant loss of phytosterols was observed during the process. Microbial
      fermentation of SODD is a potential approach to concentrate phytosterols before
      the recovery of phytosterols from SODD. During SODD fermentation, sterols-rich
      yeast cells were produced and the content of total sterols was as high as 6.96 %,
      but its major sterol was not ergosterol, which is the major sterol encountered in
      Saccharomyces cerevisiae. Except ergosterol, other sterols synthesized in the
      cells need to be identified. 

PMID- 24297327
TI  - A tight association in two genetically unlinked dispersal related traits in
      sympatric and allopatric salt marsh beetle populations.
AB  - Local adaptation likely involves selection on multiple, genetically unlinked
      traits to increase fitness in divergent habitats. Conversely, recombination is
      expected to counteract local adaptation under gene flow by breaking down adaptive
      gene combinations. Western European populations of the salt marsh beetle Pogonus
      chalceus are characterized by large interpopulation variation at various
      geographical ranges in two traits related to dispersal ability, i.e. wing size
      and different allozymes of the mitochondrial NADP(+)-dependent isocitrate
      dehydrogenase (mtIdh) gene. In this study, we tested whether variation in wing
      length was as strongly genetically determined in locally adapted populations in a
      sympatric mosaic compared to allopatric populations, and if variation in mtIDH
      and wing size was genetically unlinked. We demonstrate that the genetic
      determination of wing size is very high (h (2) = 0.90) in sympatry and of
      comparable magnitude as geographically separated populations. Second, we show
      that, although frequencies of mtIDH allozymes are tightly associated with mean
      population wing size across Western European populations, the correlation is
      strongly reduced within some of the populations. These findings demonstrate that
      the divergence involves at least two traits under independent genetic control and
      that the genetically distinct ecotypes are retained at geographical distances
      with ample opportunity for gene flow.

PMID- 24297329
TI  - How self-determined choice facilitates performance: a key role of the
      ventromedial prefrontal cortex.
AB  - Recent studies have documented that self-determined choice does indeed enhance
      performance. However, the precise neural mechanisms underlying this effect are
      not well understood. We examined the neural correlates of the facilitative
      effects of self-determined choice using functional magnetic resonance imaging
      (fMRI). Participants played a game-like task involving a stopwatch with either a
      stopwatch they selected (self-determined-choice condition) or one they were
      assigned without choice (forced-choice condition). Our results showed that self
      determined choice enhanced performance on the stopwatch task, despite the fact
      that the choices were clearly irrelevant to task difficulty. Neuroimaging results
      showed that failure feedback, compared with success feedback, elicited a drop in
      the vmPFC activation in the forced-choice condition, but not in the self
      determined-choice condition, indicating that negative reward value associated
      with the failure feedback vanished in the self-determined-choice condition.
      Moreover, the vmPFC resilience to failure in the self-determined-choice condition
      was significantly correlated with the increased performance. Striatal responses
      to failure and success feedback were not modulated by the choice condition,
      indicating the dissociation between the vmPFC and striatal activation pattern.
      These findings suggest that the vmPFC plays a unique and critical role in the
      facilitative effects of self-determined choice on performance. 

PMID- 24297328
TI  - Hypocretin (orexin) regulates glutamate input to fast-spiking interneurons in
      layer V of the Fr2 region of the murine prefrontal cortex.
AB  - We studied the effect of hypocretin 1 (orexin A) in the frontal area 2 (Fr2) of
      the murine neocortex, implicated in the motivation-dependent goal-directed tasks.
      In layer V, hypocretin stimulated the spontaneous excitatory postsynaptic
      currents (EPSCs) on fast-spiking (FS) interneurons. The effect was accompanied by
      increased frequency of miniature EPSCs, indicating that hypocretin can target the
      glutamatergic terminals. Moreover, hypocretin stimulated the spontaneous
      inhibitory postsynaptic currents (IPSCs) on pyramidal neurons, with no effect on
      miniature IPSCs. This action was prevented by blocking 1) the ionotropic
      glutamatergic receptors; 2) the hypocretin receptor type 1 (HCRTR-1), with SB
      334867. Finally, hypocretin increased the firing frequency in FS cells, and the
      effect was blocked when the ionotropic glutamate transmission was inhibited.
      Immunolocalization confirmed that HCRTR-1 is highly expressed in Fr2,
      particularly in layer V-VI. Conspicuous labeling was observed in pyramidal neuron
      somata and in VGLUT1+ glutamatergic terminals, but not in VGLUT2+ fibers (mainly
      thalamocortical afferents). The expression of HCRTR-1 in GABAergic structures was
      scarce. We conclude that 1) hypocretin regulates glutamate release in Fr2; 2) the
      effect presents a presynaptic component; 3) the peptide control of FS cells is
      indirect, and probably mediated by the regulation of glutamatergic input onto
      these cells. 

PMID- 24297330
TI  - Structural characterization of rhamnolipid produced by Pseudomonas aeruginosa
      strain FIN2 isolated from oil reservoir water.
AB  - Biosurfactant-producing microorganisms inhabiting oil reservoirs are of great
      potential in industrial applications. Yet, till now, the knowledge about the
      structure and physicochemical property of their metabolites are still limited.
      The aim of this study was to purify and structurally characterize the
      biosurfactant from Pseudomonas aeruginosa strain FIN2, a newly isolated strain
      from an oil reservoir. The purification was conducted by silica gel column
      chromatography followed by pre-RP HPLC and the structural characterization was
      carried out by GC-MS combined with MS/MS. The results show that the biosurfactant
      produced by FIN2 is rhamnolipid in nature and its four main fractions were
      identified to be Rha-C10-C10(46.1 %), Rha-Rha-C10-C10(20.1 %), Rha-C8-C10 (7.5 %)
      and Rha-C10-C12:1(5.5 %), respectively. Meanwhile, the rarely reported
      rhamnolipid congeners containing beta-hydroxy fatty acids of C6, C9, C10:1 and
      C11 were also proved to be present in the rhamnolipid mixture produced. The
      rhamnolipid mixture exhibited a strong surface activity by lowering the surface
      tension of distilled water to 28.6 mN/m with a CMC value of 195 mg/l.

PMID- 24297332
TI  - Authors' reply to the letter to the editor of P.M. Foye et al. concerning "CT
      Morphology and Morphometry of the normal adult coccyx" by Woon JT et al. (2013);
      Eur Spine J 22(4):863-870.

PMID- 24297331
TI  - Cell sources for nucleus pulposus regeneration.
AB  - PURPOSE: There is increasing interest in the development of cell therapy as a
      possible approach for the treatment of degenerative disc disease. To regenerate
      nucleus pulposus tissue, the cells must produce an appropriate proteoglycan-rich
      matrix, as this is essential for the functioning of the intervertebral disc. The
      natural environment within the disc is very challenging to implanted cells,
      particularly if they have been subcultured in normal laboratory conditions. The
      purpose of this work is to discuss parameters relevant to translating different
      proposed cell therapies of IVD into clinical use. RESULTS: Several sources of
      cells have been proposed, including nucleus pulposus cells, chondrocytes and
      mesenchymal stem cells derived from bone marrow or adipose tissue. There are some
      clinical trials and reports of attempts to regenerate nucleus pulposus utilising
      either autologous or allogenic cells. While the published results of clinical
      applications of these cell therapies do not indicate any safety issues,
      additional evidence will be needed to prove their long-term efficacy. CONCLUSION:
      This article discusses parameters relevant for successful translation of research
      on different cell sources into clinically applicable cell therapies: the
      influence of the intervertebral disc microenvironment on the cell phenotype,
      issues associated with cell culture and technical preparation of cell products,
      as well as discussing current regulatory requirements. There are advantages and
      disadvantages of each proposed cell type, but no strong evidence to favour any
      one particular cell source at the moment.

PMID- 24297333
TI  - Fisetin inhibits migration, invasion and epithelial-mesenchymal transition of
      LMP1-positive nasopharyngeal carcinoma cells.
AB  - Fisetin (3,3',4',7-tetrahydroxyflavone) has been reported to possess certain
      anticancer properties. It may inhibit tumor cell proliferation, metastasis and
      induce apoptosis. However, the effects of fisetin in preventing the metastasis of
      nasopharyngeal carcinoma (NPC) cells remain to be determined. The epithelial
      mesenchymal transition (EMT) is involved in several metastatic malignancies
      including NPC. It has been reported that the Epstein-Barr virus latent membrane
      protein-1 (LMP1) induced EMT and is associated with the metastasis of NPC. The
      aim of this study was to examine the effects of fisetin in preventing the
      migration and invasion of LMP1-expressing NPC cells (CNE1-LMP1 cells), as well as
      to investigate whether fisetin may inhibit the molecular changes associated with
      EMT induced by LMP1. The investigation demonstrated that fisetin suppressed the
      migration and invasion of CNE1-LMP1 cells under non-cytotoxic concentrations.
      Fisetin inhibited molecular changes associated with EMT induced by LMP1,
      upregulated the epithelial marker, E-cadherin protein, and downregulated the
      mesenchymal marker, vimentin protein, levels. Fisetin also significantly reduced
      the levels of Twist protein, an EMT regulator. The investigation suggested that
      fisetin inhibits the migration and invasion of LMP1-positive NPC cells, and the
      molecular mechanism involves fisetin reversing the EMT induced by LMP1 and
      downregulates the expression of Twist. This study indicated that fisetin serves
      as a potential candidate for the treatment of cancer metastasis. 

PMID- 24297334
TI  - Assessment of the association between hOGG1 C8069G polymorphism and colorectal
      cancer.
AB  - Human oxoguanine glycosylase 1 (hOGG1) is an important part in the base excision
      repair (BER) pathway of DNA repair. Numerous epidemiological studies were
      published to assess the association between hOGG1 C8069G polymorphism and risk of
      colorectal cancer, but they reported contradictory results. A meta-analysis was
      performed to clarify the effect of hOGG1 C8069G polymorphism on colorectal
      cancer. The association was assessed by calculating the pooled odds ratio (OR)
      with 95% confidence interval (95 %CI). Twenty-one studies with a total of 14,492
      participants were finally included into the meta-analysis. Overall, there was an
      obvious association between hOGG1 C8069G polymorphism and increased risk of
      colorectal cancer under all four genetic models (G vs. C: OR = 1.17, 95%CI 1.05
      1.30, P = 0.003; GG vs. CC: OR = 1.39, 95%CI 1.11-1.74, P = 0.004; GG/CG vs. CC:
      OR = 1.20, 95%CI 1.04-1.37, P = 0.010; GG vs. CC/CG: OR = 1.23, 95%CI 1.03-1.46,
      P = 0.020). Subgroup analysis based on ethnicity showed that there was an obvious
      association between hOGG1 C8069G polymorphism and increased risk of colorectal
      cancer in the Caucasian population but not in the Asian population. The findings
      from the meta-analysis suggest that there is an obvious association between hOGG1
      C8069G polymorphism and increased risk of colorectal cancer, especially in the
      Caucasian population.

PMID- 24297335
TI  - Changes in the expression of cyclin G2 in esophageal cancer cell and its
      significance.
AB  - This study aimed to analyze the expression, clinical significance of cyclin G2
      (CCNG2) in esophageal carcinoma, and the biological effect in its cell line by
      CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze
      CCNG2 protein expression in 73 cases of esophageal cancer and normal tissues to
      study the relationship between CCNG2 expression and clinical factors. CCNG2
      lentiviral vector and empty vector were respectively transfected into esophageal
      cancer Eca-109 cell line. Reverse transcription-polymerase chain reaction and
      western blot were used to detect the mRNA level and protein of CCNG2. MTT assay
      and cell cycle were also conducted as to the influence of the upregulated
      expression of CCNG2 that might be found on Eca-109 cell's biological effect.
      Immunohistochemistry: The level of CCNG2 protein expression was found to be
      significantly lower in esophageal cancer tissue than normal tissues (P < 0.05).
      Western blot: The relative amount of CCNG2 protein in esophageal cancer tissue
      was respectively found to be significantly lower than in normal tissues (P <
      0.05). The level of CCNG2 protein expression was not correlated with gender, age,
      and tumor size (P > 0.05), but it was correlated with lymph node metastasis,
      clinic stage, and histological grades (P < 0.05). Loss of CCNG2 expression
      correlated significantly with poor overall survival time by Kaplan-Meier
      analysis. The result of the biological function showed that Eca-109 cell
      transfected CCNG2 had a lower survival fraction, more percentage of the G0/G1
      phases (P < 0.05), and lower cyclin-dependent kinase 2 (CDK2) protein expression.
      CCNG2 expression decreased in esophageal cancer and correlated significantly with
      lymph node metastasis, clinic stage, histological grade, and poor overall
      survival, suggesting that CCNG2 may play important roles as a negative regulator
      to esophageal cancer cell by promoting degradation of CDK2.

PMID- 24297336
TI  - Genetic variations at microRNA and processing genes and risk of oral cancer.
AB  - Genetic variations at microRNA and microRNA processing genes are known to confer
      risk of cancer in different populations. Here, we studied variations at eight
      microRNA (miRNA) and four miRNA processing genes in 452 controls and 451 oral
      cancer patients by TaqMan genotyping assays. Variant allele-containing genotypes
      at mir-196a2 and variant allele homozygous genotype at Ran increased the risk of
      cancer significantly [adjusted odds ratio (OR) (95% confidence interval (CI)) =
      1.3 (1-1.7) and 2.3 (1.1-4.6), respectively]. Conversely, variant allele
      containing genotypes at mir-34b and variant allele homozygous genotype at Gemin3
      reduced the risk of cancer significantly [adjusted OR (95% CI) = 0.7 (0.5-0.9)
      and 0.6 (0.4-1), respectively]. Cumulative risk was also increased by three times
      with increase in the number of risk alleles at these four loci. In tobacco
      stratified analysis, variant allele homozygous genotypes at mir-29a and Ran
      increased [adjusted OR (95% CI) = 1.5 (1-2.3) and 3 (1.1-8.4) respectively],
      while variant allele-containing genotypes at mir-34b decreased [adjusted OR (95%
      CI) = 0.6 (0.4-0.9)] the risk of cancer significantly. Thus, genetic variation at
      miRNA and processing genes altered the risk of oral cancer in this population
      thereby corroborating studies in other populations. However, it is necessary to
      validate this result in different Indian sub populations with larger sample sizes
      and examine the effect of these variations in tumour tissues to explain the
      mechanism of risk alteration.

PMID- 24297337
TI  - APE1/Ref-1 enhances DNA binding activity of mutant p53 in a redox-dependent
      manner.
AB  - Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual
      function protein; in addition to its DNA repair activity, it can stimulate DNA
      binding activity of numerous transcription factors as a reduction-oxidation
      (redox) factor. APE1/Ref-1 has been found to be a potent activator of wild-type
      p53 (wtp53) DNA binding in vitro and in vivo. Although p53 is mutated in most
      types of human cancer including hepatocellular carcinoma (HCC), little is known
      about whether APE1/Ref-1 can regulate mutant p53 (mutp53). Herein, we reported
      the increased APE1/Ref-1 protein and accumulation of mutp53 in HCC by
      immunohistochemistry. Of note, it was observed that APE1/Ref-1 high-expression
      and mutp53 expression were associated with carcinogenesis and progression of HCC.
      To determine whether APE1/Ref-1 regulates DNA binding of mutp53, we performed
      electromobility shift assays (EMSAs) and quantitative chromatin
      immunoprecipitation (ChIP) assays in HCC cell lines. In contrast to sequence
      specific and DNA structure-dependent binding of wtp53, reduced mutp53 efficiently
      bound to nonlinear DNA, but not to linear DNA. Notably, overexpression of
      APE1/Ref-1 resulted in increased DNA binding activity of mutp53, while
      downregulation of APE1/Ref-1 caused a marked decrease of mutp53 DNA binding. In
      addition, APE1/Ref-1 could not potentiate the accumulation of p21 mRNA and
      protein in mutp53 cells. These data indicate that APE1/Ref-1 can stimulate mutp53
      DNA binding in a redox-dependent manner.

PMID- 24297338
TI  - Streptococcal Toxic Shock syndrome.
AB  - Streptococcal Toxic Shock syndrome (STSS) is a serious complication caused by
      exotoxins of Group A Streptococcus (GAS). It presents with fulminant shock and
      rash, is rapidly progressive with Multi-Organ Dysfunction Syndrome (MODS) and
      requires aggressive therapy with fluids, antibiotics and source control. 

PMID- 24297339
TI  - "Miniature puberty" in an eight-days-old female neonate.

PMID- 24297340
TI  - Unusual cause of hypocalcemic seizures in a neonate.

PMID- 24297341
TI  - Sweat test in patients with congenital primary hypothyroidism.

PMID- 24297342
TI  - SHP2 promotes laryngeal cancer growth through the Ras/Raf/Mek/Erk pathway and
      serves as a prognostic indicator for laryngeal cancer.
AB  - The overall survival rate and prognosis of patients with laryngeal cancer are not
      optimistic despite advances in therapeutic techniques. Gene expression prognostic
      models enable the development of more appropriate treatment strategies. The human
      gene PTPN11 encoding a non-receptor protein tyrosine phosphatase, Src homology
      phosphotyrosine phosphatase 2 (SHP2), is a well-documented proto-oncogene in
      various malignancies. This study investigated the role of SHP2 expression and
      associated clinical manifestations in laryngeal cancer using a tissue microarray
      of 112 pairs of laryngeal cancer samples and corresponding adjacent normal
      mucosae. SHP2 expression increased in laryngeal cancer, and this result was
      associated with the poor survival rate of laryngeal cancer patients. Moreover,
      increased SHP2 expression remarkably promoted the growth of laryngeal cancer
      cells in vitro and tumorigenicity of laryngeal cancer cells in vivo. The
      Ras/Raf/Mek/Erk pathway was also found to be involved in the SHP2-induced growth
      of laryngeal cancer cells. Overall, our findings indicated that SHP2 plays an
      important role in laryngeal cancer tumorigenesis and that its expression is
      negatively correlated with the prognosis of patients. Thus, SHP2 may be a
      promising combinational therapeutic target for treatment of laryngeal cancer. The
      interference of SHP2 expression can serve as a novel strategy for laryngeal
      cancer treatment.

PMID- 24297343
TI  - Compliance with quality prescribing indicators linked to financial incentives:
      what about not incentivized indicators?: an observational study.
AB  - OBJECTIVE: The aims of this study were to investigate whether general
      practitioners (GPs) who complied with quality prescribing indicators included in
      the pay-for-performance programmes also complied with quality prescribing
      indicators which are not linked to incentives and to compare the prescribing
      behaviour between those GPs who showed compliance with quality prescribing
      indicators linked to financial incentives and those who did not. DESIGN AND
      METHODOLOGY: This was a descriptive cross-sectional study which was conducted in
      2007 in the Aljarafe Primary Care Area (Andalusia, Spain) and involved 37 Health
      Care Centres and 176 GPs. The main outcome was the results of a comparison of six
      quality prescribing indicators linked to incentives and 14 quality prescribing
      indicators not linked to incentives. The chi-square test was used to compare
      qualitative variables. Quantitative variables were tested using Student's t test
      upon confirmation of normality. RESULTS: Those GPs showing compliance with the
      indicators included in the pay-for performance programme showed low levels of
      compliance with quality prescribing indicators that were unincentivised. With
      respect to compliance with the indicators not linked to financial incentives, we
      found no statistical difference between GPs who showed compliance with
      incentivised indicators (n = 57) and those showing non-compliance (n = 112) in
      terms of drug selection, with the exception of the selection of second- and third
      line antibiotics and antihistamines, nor in terms of the appropriate use of drugs
      linked to patient's clinical conditions. CONCLUSIONS: The compliance of GPs
      showing compliance with quality prescribing indicators included in pay-for
      performance programmes was not better than that of those who showed no compliance
      with other relevant quality prescribing indicators not linked to financial
      incentives.

PMID- 24297344
TI  - Improved accuracy of anticoagulant dose prediction using a pharmacogenetic and
      artificial neural network-based method.
AB  - BACKGROUND: The unpredictability of acenocoumarol dose needed to achieve target
      blood thinning level remains a challenge. We aimed to apply and compare a
      pharmacogenetic least-squares model (LSM) and artificial neural network (ANN)
      models for predictions of acenocoumarol dosing. METHODS: LSM and ANN models were
      used to analyze previously collected data on 174 participants (mean age: 67.45 SD
      13.49 years) on acenocoumarol maintenance therapy. The models were based on
      demographics, lifestyle habits, concomitant diseases, medication intake, target
      INR, and genotyping results for CYP2C9 and VKORC1. LSM versus ANN performance
      comparisons were done by two methods: by randomly splitting the data as 50 %
      derivation and 50 % validation cohort followed by a bootstrap of 200 iterations,
      and by a 10-fold leave-one-out cross-validation technique. RESULTS: The ANN-based
      pharmacogenetic model provided higher accuracy and larger R value than all other
      LSM-based models. The accuracy percentage improvement ranged between 5 % and 24 %
      for the derivation cohort and between 12 % and 25 % for the validation cohort.
      The increase in R value ranged between 6 % and 31 % for the derivation cohort and
      between 2 % and 31 % for the validation cohort. ANN increased the percentage of
      accurately dosed subjects (mean absolute error <=1 mg/week) by 14.1 %, reduced
      the percentage of mis-dosed subjects (mean absolute error 2-3 mg/week) by 7.04 %,
      and reduced the percentage of grossly mis-dosed subjects (mean absolute error >=4
      mg/week) by 24 %. CONCLUSIONS: ANN-based pharmacogenetic guidance of
      acenocoumarol dosing reduces the error in dosing to achieve target INR. These
      results need to be ascertained in a prospective study.

PMID- 24297345
TI  - Drug-induced agranulocytosis in the Berlin case-control surveillance study.
AB  - PURPOSE: Drug-induced agranulocytosis (DIAG) is a rare but serious adverse drug
      reaction. The Berlin Case-Control Surveillance Study (FAKOS) aimed to identify
      pharmaceuticals with an increased risk for this condition. METHODS: Adult
      patients with acute non-chemotherapy-induced agranulocytosis, developed in
      hospital or in the outpatient setting, were ascertained by active surveillance in
      all 51 Berlin hospitals between the years 2000 and 2010. Applying the criteria of
      the World Health Organization, a standardized drug causality assessment was
      conducted for each agranulocytosis patient to determine possible drug aetiology.
      Drug risks were quantified in a case-control design with unconditional logistic
      regression analysis. RESULTS: Sixty-three out of 88 validated cases of
      agranulocytosis were identified as being at least probably drug-related. Drug
      causality assessment resulted in 36 pharmaceuticals with a certain or probable
      relationship to agranulocytosis. Drugs involved in >= 3 cases with a probable or
      certain causality were metamizole (dipyrone) (N = 10), clozapine (N = 6),
      sulfasalazine (N = 5), thiamazole (N = 5), and carbamazepine (N = 3). In case
      control analysis, six drugs were identified with significant odds ratios for
      DIAG. The highest odds ratios were observed for clozapine, sulfasalazine, and
      thiamazole. CONCLUSIONS: Our findings are generally in agreement with those of
      earlier case-control studies. The spectrum of drugs causing acute agranulocytosis
      has not changed considerably over recent years, despite many newly marketed
      drugs. Evidence for induction of agranulocytosis by some new pharmaceuticals is
      supported.

PMID- 24297346
TI  - MiniPEG-gammaPNA.
AB  - Peptide nucleic acids (PNAs) are attractive, as compared to other classes of
      oligonucleotides that have been developed to date, in that they are relatively
      easy to synthesize and modify, hybridize to DNA and RNA with high affinity and
      sequence selectivity, and are resistant to enzymatic degradation by proteases and
      nucleases; however, the downside is that they are only moderately soluble in
      aqueous solution. Herein we describe the protocols for synthesizing the second
      generation gammaPNAs, both the monomers and oligomers, containing MiniPEG side
      chain with considerable improvements in water solubility, biocompatibility, and
      hybridization properties. 

PMID- 24297347
TI  - Cyclopentane peptide nucleic acids.
AB  - Incorporating a cyclopentane ring into the two-carbon unit of a peptide nucleic
      acid backbone increases its binding affinity to complementary nucleic acid
      sequences. This approach is a general method to improve binding and can be
      applied at either purine or pyrimidine bases. 

PMID- 24297348
TI  - Chiral PNAs with constrained open-chain backbones.
AB  - Chiral open-chain PNAs have been shown to have improved properties in terms of
      control of helical handedness, DNA affinity, sequence selectivity, and cellular
      uptake. They can be synthesized either using preformed chiral monomers or by
      means of a submonomeric strategy. The former is preferred when only a stereogenic
      center is present at C-5, whereas for PNA-bearing substituents at C-2, the
      submonomeric approach is preferred, since racemization, generally occurring
      during the solid-phase synthesis, can be minimized by this procedure. Here we
      describe the protocols for the synthesis of PNA oligomers containing C-2- or C-5-
      (or both) modified monomers and a GC method for checking the optical purity of C
      2-modified PNAs.

PMID- 24297349
TI  - Synthesis, characterization, and evaluation of radiometal-containing peptide
      nucleic acids.
AB  - Peptide nucleic acids (PNAs) have very attractive properties for applications in
      nuclear medicine. Because PNAs have high selectivity for DNA/RNA recognition,
      resistance to nuclease/protease degradation, and high thermal and radiolytic
      stabilities, PNA bioconjugates could transform the areas of diagnostic and
      therapeutic nuclear medicine. In this book chapter, we report on the current
      developments towards the preparation of radiometal-containing PNA constructs and
      summarize the protocols for labeling these probes with (99m)Tc, (111)In, (64)Cu,
      (90)Y, and (177)Lu. 

PMID- 24297350
TI  - Preparation of metal-containing peptide nucleic acid bioconjugates on the solid
      phase.
AB  - Peptide nucleic acids (PNAs) are a class of artificial DNA/RNA analogues that
      have unique physicochemical properties, which include a high chemical stability,
      resistance to nucleases and proteases, and higher mismatch sensitivity than DNA.
      PNAs were initially anticipated to be useful for application in antisense and
      antigene therapies; however, their poor cellular uptake has limited their use for
      such purposes in the "real world." Recently, it has been shown that the addition
      of metal complexes to these oligonucleotide analogues could open up new avenues
      for their utilization in various research fields. Such metallo-constructs have
      shown great promise, for a diverse range of applications, most notably in the
      biosensing area. In this book chapter, we report on the recent synthetic advances
      towards the preparation of these "(multi-)metallic PNAs" on the solid phase.

PMID- 24297351
TI  - Formation and characterization of PNA-containing heteroquadruplexes.
AB  - The guanine quadruplex is a secondary structure formed by DNA and RNA that has
      been implicated in regulation of gene expression and maintenance of genome
      stability. Guanine-rich PNA oligomers can invade DNA or RNA quadruplex targets to
      form heteroquadruplex structures. Affinities in the low nanomolar range are
      routinely observed, making PNAs among the tightest binding of all quadruplex
      targeted agents. Although inherently more promiscuous than heteroduplex formation
      based on Watson-Crick pairing, selectivity of heteroquadruplex formation can be
      improved through rational design of the sequence and backbone structure of the
      PNA. This chapter presents design rules and methods for characterizing PNA
      DNA/RNA heteroquadruplexes.

PMID- 24297352
TI  - Sequence selective recognition of double-stranded RNA using triple helix-forming
      peptide nucleic acids.
AB  - Noncoding RNAs are attractive targets for molecular recognition because of the
      central role they play in gene expression. Since most noncoding RNAs are in a
      double-helical conformation, recognition of such structures is a formidable
      problem. Herein, we describe a method for sequence-selective recognition of
      biologically relevant double-helical RNA (illustrated on ribosomal A-site RNA)
      using peptide nucleic acids (PNA) that form a triple helix in the major grove of
      RNA under physiologically relevant conditions. Protocols for PNA preparation and
      binding studies using isothermal titration calorimetry are described in detail. 

PMID- 24297353
TI  - Assembly of PNA-tagged small molecules, peptides, and carbohydrates onto DNA
      templates: programming the combinatorial pairing and inter-ligand distance.
AB  - The biochemical stability and desirable hybridization properties of peptide
      nucleic acids (PNA) coupled to the robustness of the peptidic chemistry involved
      in their oligomerization make them an attractive nucleic acid tag to encode
      molecules and program their assembly into higher order oligomers. The ability to
      program the dimerization of ligands with controlled distance between the ligands
      has important applications in emulating multimeric interactions. Additionally,
      the ability to program different permutations of ligand assemblies in a
      combinatorial fashion provides access to a broad diversity and offers a rapid
      screening method for fragment based approaches to drug discovery. Herein, we
      describe protocols to covalently link diverse carbohydrates, peptides, or small
      molecules to PNA and combinatorially assemble them in solution onto libraries of
      DNA templates or onto DNA microarrays using a commercial platform without
      recourse to specialized equipment or heavy upfront investment. 

PMID- 24297354
TI  - Site-selective scission of human genome using PNA-based artificial restriction
      DNA cutter.
AB  - Site-selective scission of genomes is quite important for future biotechnology.
      However, naturally occurring restriction enzymes cut these huge DNAs at too many
      sites and cannot be used for this purpose. Recently, we have developed a
      completely chemistry-based artificial restriction DNA cutter (ARCUT) by combining
      a pair of pseudo-complementary PNA (pcPNA) strands (sequence recognition moiety)
      and Ce(IV)/EDTA complex (molecular scissors). The scission site of ARCUT and its
      scission specificity can be freely modulated in terms of the sequences and
      lengths of the pcPNA strands so that even huge genomes can be selectively cut at
      only one predetermined site. In this chapter, the method of site-selective
      scission of human genomic DNA using ARCUT is described in detail. 

PMID- 24297355
TI  - PNA openers and their applications for bacterial DNA diagnostics.
AB  - The unique ability of triplex-forming PNAs to invade the double helix has made it
      possible to develop a highly specific and sensitive approach for bacterial
      detection. The method uses short, about 20-bp-long, signature sequences presented
      as a single copy in the bacterial genome. Bacterial cells are fixed on slides and
      the PD-loop structure is assembled on the signature site with the help of PNA
      openers, which includes the circular probe. The sensitivity of the method is
      achieved via Rolling Circle Amplification (RCA) of the circular probe. The
      obtained amplicon is detected using short ssDNA decorator probes carrying
      fluorophores and via standard fluorescent microscopy. 

PMID- 24297356
TI  - DNA-templated native chemical ligation of functionalized peptide nucleic acids: a
      versatile tool for single base-specific detection of nucleic acids.
AB  - Single base-specific detection of DNA/RNA sequences is of importance in the
      diagnosis of disease-associated genetic disorders or early stage cancer. This
      chapter introduces DNA-templated native chemical PNA ligation as a potentially
      useful tool for the sequence specific detection of nucleic acids. The template
      induced alignment of PNA-thioesters and 1,2-aminothiol-PNAs in close proximity
      leads to an increase in their effective molarities. This facilitates PNA ligation
      to proceed at concentrations where no reaction would be possible in absence of
      the template. Moreover, hybridization of the rather short PNA conjugates with non
      complementary DNA/RNA is disfavored, which prevents PNA ligation to occur on
      single base-mismatched templates. Different readout strategies of the ligation
      reaction such as HPLC, MALDI-TOF-MS and fluorecence monitoring are discussed, and
      examples for the detection of a point mutation within single stranded and PCR
      amplified double stranded DNA are provided. 

PMID- 24297357
TI  - Use of peptide nucleic acids (PNAs) for genotyping by solution and surface
      methods.
AB  - Peptide nucleic acids (PNAs) are synthetic oligonucleotide analogues based on a
      pseudopeptide backbone that bind complementary DNA or RNA with high affinity and
      specificity. In this chapter, three PNA-based genotyping assays are described:
      PCR clamping, fluorescence-based recognition, and microarray platform. The first
      two methods are performed in solution, while the microarray method uses a solid
      surface. 

PMID- 24297358
TI  - Analysis of PNA hybridization by surface plasmon resonance.
AB  - Reactions templated by a specific nucleic acid sequence have emerged as an
      attractive strategy for nucleic acid sensing. The Staudinger reaction using an
      azide-quenched fluorophore and a phosphine is particularly well suited by virtue
      of its bioorthogonality and biocompatibility. The reaction is promoted by a
      complementary nucleic acid that aligns the phosphine with the azide-quenched
      fluorophore. Cellular RNAs can catalyze the Staudinger reaction, and signal
      amplification can be achieved through multiple turnover of the template. Peptide
      nucleic acids (PNAs) provide a convenient platform for the preparation of
      specific probes as they combine desirable hybridization properties, robust
      synthesis, ease of fluorophore conjugation, and high biochemical stability.
      Herein, we describe protocols for fast fluorescent detection of miRNAs in human
      cells with PNA-based probes via reductive unquenching of bis-azidorhodamine by
      trialkylphosphine.

PMID- 24297359
TI  - PNA fluorescent in situ hybridization (FISH) for rapid microbiology and
      cytogenetic analysis.
AB  - Hybridization-based assays for the detection of nucleic acids including in situ
      hybridization are increasingly being utilized in a wide variety of disciplines
      such as cytogenetics, microbiology, and histology. Generally in situ
      hybridization assays utilize either cloned genomic probes for the detection of
      DNA sequences or oligonucleotide probes for the detection of DNA or RNA
      sequences. Alternately, PNA probes are increasingly being utilized in a variety
      of in situ hybridization assays. The neutral backbone of the PNA molecule allows
      for the PNA probes to bind to DNA or RNA under low ionic strength conditions that
      will either disfavor reannealing of complimentary genomic sequences or are
      denaturing for RNA secondary structure but are favorable for PNA/DNA or PNA/RNA
      hybridization. For in situ hybridization assays these unique properties of PNA
      probes offer significant advantages that allow for the development of fast,
      simple, and robust assays (Figs. 14.1 and 14.2).

PMID- 24297360
TI  - Rapid miRNA imaging in cells using fluorogenic templated Staudinger reaction
      between PNA-based probes.
AB  - Reactions templated by a specific nucleic acid sequence have emerged as an
      attractive strategy for nucleic acid sensing. The Staudinger reaction using an
      azide-quenched fluorophore and a phosphine is particularly well suited by virtue
      of its bioorthogonality and biocompatibility. The reaction is promoted by a
      complementary nucleic acid that aligns the phosphine with the azide-quenched
      fluorophore. Cellular RNAs can catalyze the Staudinger reaction and signal
      amplification can be achieved through multiple turnover of the template. Peptide
      nucleic acids (PNA) provide a convenient platform for the preparation of specific
      probes as they combine desirable hybridization properties, robust synthesis, ease
      of fluorophore conjugation, and high biochemical stability. Herein, we describe
      protocols for fast fluorescent detection of miRNAs in human cells with PNA-based
      probes via reductive unquenching of bis-azidorhodamine by trialkylphosphine. 

PMID- 24297361
TI  - Cellular delivery of peptide nucleic acids (PNAs).
AB  - Cellular delivery methods are a prerequisite for cellular studies with PNA. This
      chapter describes PNA cellular delivery using cell-penetrating peptide (CPP)-PNA
      conjugates and transfection of PNA-ligand conjugates mediated by cationic lipids.
      Furthermore, two endosomolytic procedures employing chloroquine treatment or
      photochemical internalization (PCI) for significantly improving PNA delivery
      efficacy are described. 

PMID- 24297362
TI  - Peptide nucleic acid-mediated recombination for targeted genomic repair and
      modification.
AB  - The ability to directly manipulate the human genome to correct a disease-related
      mutation, introduce a sequence change that would lead to site-specific gene
      knockout, or increase gene expression is a very powerful tool with tremendous
      clinical value. Triplex formation by synthetic DNA-binding molecules such as
      peptide nucleic acids (PNAs) has been studied for over 20 years and much of the
      work in the last 10 years has shown its great promise in its use to direct site
      specific gene modification for the use in gene therapy. In this chapter, detailed
      protocols are described for the design and use of triplex-forming PNAs to bind
      and mediate gene modification at specific chromosomal targets. Target site
      identification, PNA and donor oligonucleotide design, in vitro characterization
      of binding, optimization with reporter systems, as well as various methods to
      assess gene modification and isolate modified cells are described. 

PMID- 24297363
TI  - Antisense effects of PNAs in bacteria.
AB  - Peptide nucleic acids (PNAs) are a class of artificial DNA/RNA analogues that
      have unique physicochemical properties, which include a high chemical stability,
      resistance to nucleases and proteases and higher mismatch sensitivity than DNA.
      PNAs were initially anticipated to be useful for application in antisense and
      antigene therapies; however, their poor cellular uptake has limited their use for
      such purposes in the "real world". Recently, it has been shown that the addition
      of metal complexes to these oligonucleotide analogues could open up new avenues
      for their utilization in various research fields. Such metallo-constructs have
      shown great promise, for a diverse range of applications, most notably in the
      biosensing area. In this chapter, we report on the recent synthetic advances
      towards the preparation of these "(multi)-metallic PNAs" on the solid phase. 

PMID- 24297364
TI  - A treatment option for severe cerebellar hemorrhage with ventricular extension in
      elderly patients: intraventricular fibrinolysis.
AB  - External ventricular drainage (EVD) combined with intraventricular fibrinolysis
      (IVF) is rarely used in severe spontaneous cerebellar hemorrhage (SCH) with
      intraventricular hemorrhage (IVH). Recently, the treatment strategy was
      repeatedly performed in our hospital to elderly patients with severe SCH + IVH.
      To analyze its clinical value, we compared it to two treatment strategies which
      now commonly are used for these patients: conservative management (CM) and clot
      evacuation (CE). In this study, a total of 118 cases were observed, of which 28
      cases received CM, 43 cases received EVD + IVF and 47 cases received CE. The
      Glasgow Coma Scale score, frequency of complication, mortality in one month,
      modified Rankin Scale (mRS) at six months, and causes of death were analyzed. The
      outcomes of patients in the CM group were extremely poor compared to patients
      undergoing surgery (P = 0.034) and the mortality was up to 61.3 % (18/28), which
      was much higher than those of the two surgical groups (P = 0.026). No significant
      difference was found in mortality and mRS between the two surgical groups (P >
      0.05). Patients in the CE group mostly died of deterioration of comorbidities and
      postoperative complications, whereas more deaths occurred in the CM group and the
      EVD + IVF group due to rebleeding, brainstem compression, perilesional edema and
      tight posterior fossa (chi (2), P = 0.006). It is suggested that EVD + IVF is a
      treatment option for elderly patients with severe SCH + IVH. 

PMID- 24297365
TI  - Myoclonus-dystonia and epilepsy in a family with a novel epsilon-sarcoglycan
      mutation.
AB  - Seizures have been reported in two families with myoclonus-dystonia due to
      epsilon-sarcoglycan (SGCE) mutations. We report a Norwegian family with myoclonus
      dystonia and epilepsy associated with a novel SGCE mutation. All six manifesting
      SGCE mutation carriers had myoclonus, and dystonia was present in two patients.
      Sequencing of the SGCE gene in the proband identified a novel frameshift
      c.372delG mutation that predicts the amino acid change [p.Lys125SerfsX7] and the
      formation of a premature stop codon. The mutation segregated with myoclonus
      dystonia in the family. The typical motor symptoms were accompanied by
      generalized seizures in four of six affected mutation carriers. The seizure type
      included febrile, absence and generalized tonic-clonic seizures. One deceased
      patient with severe epilepsy and myoclonus could not be tested for the SGCE
      mutation. Seizures are rarely observed in myoclonus-dystonia patients with SGCE
      mutations, and may not be a part of the phenotype. The co-occurrence of seizures
      and myoclonus-dystonia suggests that they are both due to the same underlying
      SGCE mutation. However, with epilepsy being a relatively common disorder and lack
      of complete co-segregation in our and previous families, it is possible that some
      patients suffer from two different genetic disorders. The presence of seizures
      and EEG abnormalities should not be considered exclusion criteria for the
      diagnosis of myoclonus-dystonia. 

PMID- 24297367
TI  - Early angiographic occlusion of ruptured blister aneurysms of the internal
      carotid artery using the Pipeline Embolization Device as a primary treatment
      option.
AB  - BACKGROUND: Data on the timing, durability and occlusion rate of treating
      ruptured blister cerebral aneurysms using the Pipeline Embolization Device (PED)
      are limited. CLINICAL PRESENTATION: Three patients who presented with
      subarachnoid hemorrhages from ruptured blister aneurysms of the internal carotid
      arteries were treated with the PED. RESULTS: Aneurysmal occlusion with
      reconstruction of the parent vessels occurred angiographically using the PED as a
      primary treatment modality. All three patients were treated successfully without
      immediate or delayed complications and remained neurologically intact during the
      6-month follow-up period. CONCLUSIONS: Complete occlusion of a ruptured blister
      aneurysm can occur immediately after PED placement. In ruptured blister aneurysms
      with contrast stagnation after PED treatment, early angiographic occlusion was
      confirmed as early as 6 weeks and continued with medium-term durability.

PMID- 24297366
TI  - Renal dysfunction in acute congestive heart failure: a common problem for
      cardiologists and nephrologists.
AB  - The term acute heart failure (AHF) refers to a clinical syndrome with typical
      symptoms and signs, in which a structural or functional heart abnormality leads
      to defective oxygen delivery. The term cardiorenal syndrome has been proposed to
      outline the strict interplay between cardiac and renal function. In the setting
      of acute cardiac decompensation, acute kidney injury (AKI) is generally referred
      to as cardiorenal syndrome type 1. In this review, we summarize the fundamental
      pathophysiological aspects of both AHF and AHF-related AKI. We also review the
      latest therapeutic options, including both pharmacological ones, such as loop
      diuretics, potassium-sparing diuretics and vaptans, and non-pharmacological ones,
      such as ultrafiltration, and their impact on patients' outcome. We discuss the
      pathophysiology of diuretic resistance, a common occurrence in these patients,
      reviewing the available strategies to treat it and highlighting how a close
      collaboration between cardiologists and nephrologists is frequently crucial for
      the management of this complication. Finally, we discuss three new promising non
      pharmacological tools for the prevention of AHF recurrence, including two methods
      that exploit sympathetic denervation and one technique that acts by increasing
      vagal tone.

PMID- 24297368
TI  - Tentorial dural arteriovenous fistula manifesting as contralateral trigeminal
      neuralgia: resolution after transarterial Onyx embolization.
AB  - Tentorial dural arteriovenous fistula (DAVF) as a cause of trigeminal neuralgia
      is extremely rare. Although less than 10 cases have been reported in the
      literature, all cases presented with ipsilateral trigeminal neuralgia. Here we
      report a unique case of tentorial DAVF manifesting as contralateral trigeminal
      neuralgia. A 58-year-old man presented with right-sided trigeminal neuralgia.
      Cerebral angiography revealed a left tentorial DAVF and the MR imaging
      demonstrated a variceal venous dilatation occupying the left lateral pontine
      cistern and multiple venous flow voids adjacent to the right trigeminal nerve
      root entry zone. Transarterial Onyx embolization resulted in near complete
      obliteration of the fistula with immediate resolution of facial pain. The patient
      remains symptom free and without evidence of recurrence during 9 months of follow
      up. Transarterial Onyx embolization may be an effective treatment modality for
      such an usual case. 

PMID- 24297369
TI  - Regulation of the levels of Smad1 and Smad5 in MC3T3-E1 cells by Icariine in
      vitro.
AB  - The purpose of this study was to investigate the role of Icariine on the
      expression of Smadl and Smad5 mRNA and protein levels in MC3T3-E1 cells in vitro.
      MC3T3-E1 cells were cultured in the presence of different concentrations of
      Icariine (0, 10, 40 and 80 ng/ml). Smad1 and Smad5 mRNA levels were detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and the expression of
      proteins was determined by western blotting, immunohistochemistry staining and
      immunofluorescence. Smad1 and Smad5 mRNA levels continuously increased in 10, 40
      and 80 ng/ml of Icariine with time and the differences indicated statistical
      significance. Western blot analysis demonstrated that the Smad1 and Smad5 protein
      levels in the 10, 40 and 80 ng/ml groups were higher compared with the 0 ng/ml
      group at 24, 48 and 72 h, and the difference was statistically significant.
      Immunohistochemistry staining and immunofluorescence showed that the expression
      of the Smad1 and Smad5 proteins was higher in the cytoplasm and nuclei in the 10,
      40 and 80 ng/ml groups compared with the 0 ng/ml group. Icariine has a direct
      stimulatory function on the differentiation of MC3T3-E1 osteoblastic cells in
      vitro, which may be mediated by increasing the production of Smad1 and Smad5 in
      osteoblasts.

PMID- 24297370
TI  - Assessment of diffusion tensor imaging indices in calf muscles following postural
      change from standing to supine position.
AB  - OBJECT: To investigate whether postural change from erect to recumbent position
      affects calf muscle water diffusivity. MATERIALS AND METHODS: Ten healthy adults
      (27.2 +/- 4.9 years, 3 females) were imaged at baseline (following assumption of
      recumbent position), and after 34 min (session 2) and 64 min (session 3) of
      laying supine within a 3T MRI scanner. Diffusion tensor imaging (DTI)
      eigenvalues, fractional anisotropy (FA) and apparent diffusion coefficient (ADC)
      were evaluated in five calf muscles (anterior and posterior tibialis and triceps
      surae) during each of the three imaging sessions. RESULTS: Significant decreases
      were observed in all of the eigenvalues and ADC in each of the muscles with
      postural change. These reductions ranged from 3.2 to 6.7% and 3.4 to 7.5% for the
      various DTI metrics, following 34 and 64 min of supine rest, respectively (P <
      0.05). No significant differences were noted in ADC or eigenvalues between the
      second and third imaging sessions for any muscle. FA did not change significantly
      with postural manipulation in any muscle compartment. CONCLUSION: Diffusion
      tensor imaging indices were altered with postural change. As differences were not
      apparent between the latter two imaging sessions, we suggest that a short supine
      resting period (~34 min) is sufficient for muscle diffusivity to stabilize prior
      to quantitative MR imaging in healthy young adults.

PMID- 24297371
TI  - Genistein attenuates cancer stem cell characteristics in gastric cancer through
      the downregulation of Gli1.
AB  - Genistein is an isoflavone from soy with multiple action targets in cellular
      processes. Hedgehog signaling and its activator Gli1 are involved not only in
      oncogenesis, but also in cancer stemness and overexpression of CD44, a typical
      cancer stem cell surface marker. It has been shown that levels of Gli1 and CD44
      expression are downregulated by genistein. Genistein may modulate distinctive
      cellular characteristics in cancer stem cells by inhibiting Gli1-related
      signaling pathways. In the present study, we sorted cells from MKN45, a human
      gastric cancer cell line, according to CD44 expression. CD44(+) cells showed
      properties of cancer stem-like cells and formed sphere colonies. In addition,
      sonic hedgehog (Shh) signaling genes were upregulated in CD44(+) cells when
      compared with these levels in CD44(-) cells. When CD44(+) cancer stem-like cells
      were treated with genistein, Gli1 and CD44 mRNA and protein expression was
      significantly reduced. Moreover, other stem cell markers were downregulated by
      genistein. Gli1 siRNA was used to confirm the action of genistein in inhibiting
      Gli1 expression. The high cell migration capacity of CD44(+) cells was blocked by
      genistein. in conclusion, genistein inhibits Gli1 gene expression, resulting in
      the attenuation of cancer stem-like properties in gastric cancer cells. In
      addition, genistein suppresses the cell invasive capacity that is required for
      tumor growth and metastasis. Our data showed that genistein can be an effective
      agent for gastric cancer therapy by targeting cancer stem-like characteristics. 

PMID- 24297372
TI  - Assessment of global cardiac uptake of radiolabeled iron oxide nanoparticles in
      apolipoprotein-E-deficient mice: implications for imaging cardiovascular
      inflammation.
AB  - PURPOSE: Atherosclerosis is a leading cause of death in industrialized countries
      and is characterized by the accumulation of lipids and inflammatory cells,
      including macrophages, in blood vessel walls. Therefore, the ability to image
      macrophages could help identify plaques that are precursors of acute thrombotic
      events. Previous research has shown that long-circulating nanoparticles could be
      used to detect macrophages within atherosclerotic plaques of the aorta. By
      conducting this study, we investigated whether global cardiac uptake of
      radiolabeled nanoparticles could allow assessment of total macrophage burden in
      the coronary arteries. PROCEDURES: Dextran-coated iron oxide nanoparticles
      (IONPs) were labeled with iodine-125 via Bolton-Hunter (sulfosuccinimidyl-3-[4
      hydroxyphenyl]propionate) method. IONPs were characterized by means of dynamic
      light scattering and transmission electronic microscopy. Biodistribution studies
      were performed in healthy and atherosclerotic mice. Additionally, digital
      autoradiography of hearts from both healthy and atherosclerotic mice was
      performed to assess regional and global atherosclerotic burden. RESULTS: The
      [(125)I]IONPs exhibited high radiolabel stability and long blood circulation,
      which eventually led to high heart uptake in apoE -/- mice when compared with
      healthy controls. Furthermore, digital autoradiography showed substantially
      enhanced emission of signals from the hearts of atherosclerotic mice, while no or
      minimal cardiac signals were detected in healthy mice. CONCLUSIONS: This
      preparation showed adequate physical-chemical properties for in vivo studies,
      such as small size (~30 nm), good radiolabel stability, and long circulation
      time. There was also significant accumulation in the heart of apoE-/- mice
      compared with that of healthy control animals. These findings suggest that
      radiolabeled dextran-coated iron oxide nanoparticles may have potential to become
      a useful tool to detect macrophages in the atherosclerosis plaques of coronary
      arteries; however, these preliminary findings should be confirmed by further
      studies in a larger scale in various atherosclerosis models.

PMID- 24297373
TI  - Orthopaedic and surgical features in the management of patients with haemophilia.
AB  - Haemophilia is a hereditary disease due to a defect of the X chromosome, which
      determines a faulty production of coagulation factor VIII in haemophilia A (85%
      of cases) and factor IX in haemophilia B. Three degrees of severity can be
      distinguished: low, with a deficient factor concentration greater than 5% of
      normal values, medium, with a concentration between 1 and 5%, and severe,
      comprising more than half of haemophilia cases, with a concentration of factor
      VIII or factor IX under 1% of normal. The evolution of haemophilic arthropathy is
      almost always from haemarthrosis to chronic synovitis and extended erosions of
      the articular surface, culminating in the final stage of articular destruction
      chronic haemophilic arthropathy. This paper analyses the results of the treatment
      applied to a lot of one hundred and ten patients operated inside the our
      country's sole Compartment of Osteo-Articular Surgery of haemophiliac patients
      within the Clinic No. 2 of Orthopaedics and Traumatology between 2001 and 2013.
      This compartment was founded in 2001, being included in the Romanian Health
      Ministry's programme for financing the treatment for haemophilia. Within the
      aforementioned time period, a total of 158 patients from the entire country were
      consulted. From these, 110 patients underwent a series of surgical procedures,
      112 in total. The age interval of the studied lot was between 9 and 45 years,
      with a maximum between 11 and 20 years. With replacement therapy and correct
      surgical indication, osteoarticular surgery in haemophiliacs, performed in a
      specialized centre by a multidisciplinary team, can give good results with
      acceptable risks.

PMID- 24297374
TI  - Physicians' adherence to tight control treatment strategy and combination DMARD
      therapy are additively important for reaching remission and maintaining working
      ability in early rheumatoid arthritis: a subanalysis of the FIN-RACo trial.

PMID- 24297375
TI  - Quantitative syndesmophyte measurement in ankylosing spondylitis using CT:
      longitudinal validity and sensitivity to change over 2 years.
AB  - OBJECTIVES: Accurate measurement of syndesmophyte development and growth in
      ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments
      to slow spinal fusion. We tested the longitudinal validity and sensitivity to
      change of quantitative measurement of syndesmophytes using CT. METHODS: We
      performed lumbar spine CT scans on 33 patients with AS at baseline, 1 year and 2
      years. Volumes and heights of syndesmophytes were computed in four intervertebral
      disk spaces. We compared the computed changes to a physician's ratings of change
      based on CT scan inspection. Sensitivity to change of the computed measures was
      compared with that of the modified Stoke AS Spinal Score (radiography) and a
      scoring method based on MRI. RESULTS: At years 1 and 2, respectively 24 (73%) and
      26 (79%) patients had syndesmophyte volume increases by CT. At years 1 and 2, the
      mean (SD) computed volume increases per patient were, respectively 87 (186) and
      201 (366) mm(3). Computed volume changes were strongly associated with the
      physician's visual ratings of change (p<0.0002 and p<0.0001 for changes at years
      1 and 2, respectively). The sensitivity to change over 1 year was higher for the
      CT volume measure (1.84) and the CT height measure (1.22) than either the MRI
      measure (0.50) or radiography (0.29). CONCLUSIONS: CT-based syndesmophytes
      measurements had very good longitudinal validity and better sensitivity to change
      than radiography or MRI. This method shows promise for longitudinal clinical
      studies of syndesmophyte development and growth.

PMID- 24297376
TI  - MRP8/14 serum levels as a strong predictor of response to biological treatments
      in patients with rheumatoid arthritis.
AB  - BACKGROUND: One-third of rheumatoid arthritis (RA) patients treated with
      biological therapy show lack of response. The use of predictive biomarkers to
      identify responders to treatment may provide guidance in optimising treatment
      strategies and reduce unnecessary side effects and costs. OBJECTIVE: To test the
      ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous
      TLR-4 receptor agonist, to predict and monitor response to biologics in RA
      patients. METHODS: 170 RA patients treated with adalimumab (n=86), infliximab
      (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and
      non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4
      and 16 weeks after initiation of treatment and related to response outcome.
      RESULTS: Before initiation of treatment, responders showed significantly higher
      MRP8/14 protein complex levels compared with non-responders in each prospective
      cohort (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis
      showed that having high MRP8/14 baseline levels increased the odds of being a
      responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment,
      MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16
      weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in
      non-responders. In patients treated with rituximab, MRP8/14 levels decreased by
      59% after 16 weeks in responders and increased by 89% after 16 weeks in non
      responders. CONCLUSION: Serum concentrations of MRP8/14 protein complex are a
      promising biomarker to predict response to biological therapy in active RA
      patients at baseline and could be used to monitor response to treatment across
      different mechanisms of action.

PMID- 24297377
TI  - New insights into Chlamydia and arthritis. Promise of a cure?
AB  - Chlamydia trachomatis and Chlamydia pneumoniae together comprise the most
      frequent causative pathogens that elicit reactive arthritis (ReA). Advances in
      our understanding of the molecular biology/molecular genetics of these organisms
      have improved significantly the ability to detect chlamydiae in the joint for
      diagnostic purposes, as well as extending our current understanding of the
      pathogenic processes they elicit in the joint and elsewhere. An important aspect
      of the latter is that synovial chlamydiae infect the joint in an unusual but
      metabolically active state. While some standard treatments can provide a
      palliative effect on the ReA disease phenotype, many reports have indicated that
      standard antibiotic treatment does not provide a cure. Of critical importance,
      however, two recent reports of controlled clinical trials demonstrated that
      Chlamydia-ReA can be treated successfully using combination antibiotic therapy.
      These observations offer the opportunity of a cure for this disease, thereby
      increasing the practical importance of awareness and diagnosis of the
      spondyloarthritis caused by Chlamydia. In this viewpoint, we provide an overview
      of recent key findings in the epidemiology, pathophysiology, clinical
      manifestations, diagnosis and treatment of Chlamydia-induced arthritis. Our
      intention is for these insights to be translated rapidly into clinical practice
      to overcome misdiagnosis and underdiagnosis of the disease, and for them to
      stimulate the continued development of a cure. 

PMID- 24297379
TI  - Disease-modifying effect of strontium ranelate in a subset of patients from the
      Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in
      bone marrow lesions protects against cartilage loss.
AB  - OBJECTIVE: To explore, using MRI, the disease-modifying effect of strontium
      ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions
      (BMLs) in a subset of patients from a Phase III clinical trial in knee
      osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)).
      MATERIAL AND METHODS: Patients with primary symptomatic knee OA were randomised
      to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of
      these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee
      cartilage volume and BMLs. Missing values were imputed and the analyses were
      adjusted according to Bonferroni. RESULTS: In this MRI subset, the distribution
      of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1
      g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at
      baseline regarding demographics, clinical symptoms or imaging characteristics.
      Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12
      (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial
      femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than
      placebo. In patients with BML in the medial compartment at baseline, the BML
      score at 36 months was decreased in both treatment groups compared with the
      placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively),
      and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau
      compared with placebo. CONCLUSIONS: In knee OA patients, treatment with SrRan 2
      g/day was found to have beneficial effects on structural changes by significantly
      reducing CVL in the plateau and BML progression in the medial compartment.

PMID- 24297378
TI  - The comparative effectiveness of abatacept versus anti-tumour necrosis factor
      switching for rheumatoid arthritis patients previously treated with an anti
      tumour necrosis factor.
AB  - OBJECTIVE: We compared the effectiveness of abatacept (ABA) versus a subsequent
      anti-tumour necrosis factor inhibitor (anti-TNF) in rheumatoid arthritis (RA)
      patients with prior anti-TNF use. METHODS: We identified RA patients from a large
      observational US cohort (2/1/2000-8/7/2011) who had discontinued at least one
      anti-TNF and initiated either ABA or a subsequent anti-TNF. Using propensity
      score (PS) matching (n:1 match), effectiveness was measured at 6 and 12 months
      after initiation based on mean change in Clinical Disease Activity Index (CDAI),
      modified American College of Rheumatology (mACR) 20, 50 and 70 responses,
      modified Health Assessment Questionnaire (mHAQ) and CDAI remission in adjusted
      regression models. RESULTS: The PS-matched groups included 431 ABA and 746 anti
      TNF users at 6 months and 311 ABA and 493 anti-TNF users at 12 months. In
      adjusted analyses comparing response following treatment with ABA and anti-TNF,
      the difference in weighted mean change in CDAI (range 6-8) at 6 months (0.46, 95%
      CI -0.82 to 1.73) and 12 months was similar (-1.64, 95% CI -3.47 to 0.19). The
      mACR20 responses were similar at 6 (28-32%, p=0.73) and 12 months (35-37%,
      p=0.48) as were the mACR50 and mACR70 (12 months: 20-22%, p=0.25 and 10-12%,
      p=0.49, respectively). Meaningful change in mHAQ was similar at 6 and 12 months
      (30-33%, p=0.41 and 29-30%, p=0.39, respectively) as was CDAI remission rates (9
      10%, p=0.42 and 12-13%, p=0.91, respectively). CONCLUSIONS: RA patients with
      prior anti-TNF exposures had similar outcomes if they switched to a new anti-TNF
      as compared with initiation of ABA.

PMID- 24297380
TI  - Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase
      positive catecholaminergic cells in experimental arthritis.
AB  - OBJECTIVES: Studies in rheumatoid arthritis (RA), osteoarthritis (OA) and mice
      with arthritis demonstrated tyrosine hydroxylase-positive (TH(+)) cells in
      arthritic synovium and parallel loss of sympathetic nerve fibres. The exact
      function of TH(+) cells and mode of TH induction are not known. METHODS: Synovial
      cells of RA/OA were isolated and cultured under normoxic/hypoxic conditions
      with/without stimulating enzyme cofactors of TH and inhibitors of TH. We studied
      TH expression and release of cytokines/catecholamines. In vivo function was
      tested by cell therapy with TH(+) neuronal precursor cells (TH(+) neuronal cells)
      in DBA/1 mice with collagen type II-induced arthritis (CIA). RESULTS: Compared
      with normoxic conditions, hypoxia increased TH protein expression and
      catecholamine synthesis and decreased release of tumour necrosis factor (TNF) in
      OA/RA synovial cells. This inhibitory effect on TNF was reversed by TH inhibition
      with alpha-methyl-para-tyrosine (alphaMPT), which was particularly evident under
      hypoxic conditions. Incubation with specific TH cofactors (tetrahydrobiopterin
      and Fe(2+)) increased hypoxia-induced inhibition of TNF, which was also reversed
      by alphaMPT. To address a possible clinical role of TH(+) cells, murine TH(+)
      neuronal cells were generated from mesenchymal stem cells. TH(+) neuronal cells
      exhibited a typical catecholaminergic phenotype. Adoptive transfer of TH(+)
      neuronal cells markedly reduced CIA in mice, and 6-hydroxydopamine, which
      depletes TH(+) cells, reversed this effect. CONCLUSIONS: The anti-inflammatory
      effect of TH(+) neuronal cells on experimental arthritis has been presented for
      the first time. In RA/OA, TH(+) synovial cells have TH-dependent anti
      inflammatory capacities, which are augmented under hypoxia. Using generated TH(+)
      neuronal cells might open new avenues for cell-based therapy.

PMID- 24297381
TI  - Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with
      rheumatoid arthritis and an inadequate response to methotrexate: efficacy and
      safety results from the randomised SARIL-RA-MOBILITY Part A trial.
AB  - OBJECTIVES: To evaluate safety and efficacy of weekly (qw) and every other week
      (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor alpha (anti
      IL-6Ralpha) monoclonal antibody, for moderate-to-severe rheumatoid arthritis
      (RA). METHODS: In this dose-ranging study, patients (n=306) with active RA,
      despite methotrexate, were randomly assigned to placebo or one of five
      subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200
      mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was
      ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity
      Score in 28 joints (C reactive protein). Safety, pharmacokinetics,
      pharmacodynamics and efficacy in population subgroups were assessed. RESULTS: The
      proportion of patients achieving an ACR20 response compared with placebo was
      significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity
      adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w
      (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426)
      versus placebo. Sarilumab >=150 mg q2w reduced C reactive protein, which did not
      return to baseline between dosing intervals. Infections were the most common
      adverse event; none were serious. Changes in laboratory values (neutropenia,
      transaminases and lipids) were consistent with reports with other IL-6Ralpha
      inhibitors. CONCLUSIONS: Sarilumab improved signs and symptoms of RA over 12
      weeks in patients with moderate-to-severe RA with a safety profile similar to
      reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had
      the most favourable efficacy, safety and dosing convenience and are being further
      evaluated in Phase III.

PMID- 24297383
TI  - Methotrexate polyglutamates in erythrocytes are associated with lower disease
      activity in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG)
      concentrations in patients with rheumatoid arthritis (RA) are associated with
      disease activity or adverse events. METHODS: We used a longitudinal study design
      with two cohorts. The derivation cohort included 102 and the validation cohort
      included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5
      glutamate residues at 3 months, 6 months and 9 months after MTX start with a
      liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease
      activity score in 28 joints (DAS28) and adverse events. Longitudinal associations
      of MTX-PG concentrations after 3 months, 6 months and 9 months with DAS28 were
      tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX
      dose and comedication. RESULTS: In the derivation cohort, mean DAS28 decreased
      from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9 months. Thirty per cent
      of patients in the derivation cohort experienced more than three adverse events
      after 3 months, which decreased to 18% after 9 months. In the validation cohort,
      DAS28 and adverse events were comparable with the derivation cohort. In the
      derivation cohort, MTX-PG1 (beta=-0.005), MTX-PG2 (beta=-0.022), MTX-PG3 (beta=
      0.007) and total MTX-PG (beta=-0.004) were associated (p<0.05) with lower DAS28
      over 9 months. In the validation cohort, MTX-PG2 (beta=-0.015), MTX-PG3 (beta=
      0.010), MTX-PG4 (beta=-0.008) and total MTX-PG (beta=-0.003) were associated with
      lower DAS28 over 9 months. None of the MTX-PGs was associated with adverse
      events. CONCLUSIONS: In this first longitudinal study, we showed that an increase
      in erythrocyte-MTX-PG concentration was associated with a decreased DAS28 over 9
      months in two cohorts, and is therefore a potential tool for therapeutic drug
      monitoring of MTX in RA.

PMID- 24297382
TI  - Identification of anticitrullinated protein antibody reactivities in a subset of
      anti-CCP-negative rheumatoid arthritis: association with cigarette smoking and
      HLA-DRB1 'shared epitope' alleles.
AB  - INTRODUCTION: A hallmark of rheumatoid arthritis (RA) is the development of
      autoantibodies targeting proteins that contain citrulline. Anticitrullinated
      protein antibodies (ACPAs) are currently detected by the commercial cyclic
      citrullinated peptide (CCP) assay, which uses a mix of cyclised citrullinated
      peptides as an artificial mimic of the true antigen(s). To increase the
      sensitivity of ACPA detection and dissect ACPA specificities, we developed a
      multiplex assay that profiles ACPAs by measuring their reactivity to the
      citrullinated peptides and proteins derived from RA joint tissue. METHODS: We
      created a bead-based, citrullinated antigen array to profile ACPAs. This custom
      array contains 16 citrullinated peptides and proteins detected in RA synovial
      tissues. We used the array to profile ACPAs in sera from a cohort of patients
      with RA and other non-inflammatory arthritides, as well as sera from an
      independent cohort of RA patients for whom data were available on carriage of HLA
      DRB1 'shared epitope' (SE) alleles and history of cigarette smoking. RESULTS: Our
      multiplex assay showed that at least 10% of RA patients who tested negative in
      the commercial CCP assay possessed ACPAs. Carriage of HLA-DRB1 SE alleles and a
      history of cigarette smoking were associated with an increase in ACPA reactivity
      in anti-CCP(+) RA and in a subset of anti-CCP(-) RA. CONCLUSIONS: Our multiplex
      assay can identify ACPA-positive RA patients missed by the commercial CCP assay,
      thus enabling greater diagnostic sensitivity. Further, our findings suggest that
      cigarette smoking and possession of HLA-DRB1 SE alleles contribute to the
      development of ACPAs in anti-CCP(-) RA.

PMID- 24297384
TI  - Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia
      rheumatica: comparison with the previous criteria in a single-centre study.
AB  - OBJECTIVE: To compare the performance of published classification/diagnostic
      criteria for polymyalgia rheumatica (PMR), including the new 2012 European League
      Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, in a
      single-centre study. METHODS: We studied all consecutive patients with new-onset
      PMR seen in our centre over 6 years, whose diagnosis was confirmed during a
      prospective 12-month follow-up period. Subjects were classified by each of the
      seven different criteria. Sensitivity and specificity were compared. Control
      population consisted of all consecutive patients aged >=50 years seen in a 4-year
      period in our early arthritis clinic who had a 12-month confirmation of a
      diagnosis of rheumatoid arthritis (RA) or other inflammatory articular diseases.
      RESULTS: Data were collected from 136 cases and 149 controls, including 94
      patients with RA. The most sensitive criteria were the new 2012 EULAR/ACR
      classification criteria (92.6%). Adding ultrasound (US) specificity increased
      from 81.5% to 91.3% in total cases and from 79.7% to 89.9% in RA. Bird criteria
      had a sensitivity of 89.2% but the lowest specificity (40.2% in total cases and
      72.5% in RA). Jones and Nobunaga criteria were the most specific criteria (96.7%
      and 97.8% in total cases and 98.6% and 99.5% in RA) but the less sensitive (63.1%
      and 58.2%) ones. Overall, discriminatory ability, as reflected by the area under
      the receiver operating characteristic curve, was better for the 2012 US EULAR/ACR
      criteria (0.920 in total cases and 0.910 in RA). CONCLUSIONS: The new EULAR/ACR
      criteria in new-onset PMR patients perform best in discriminating PMR from RA and
      other inflammatory articular diseases. Ultrasound further increases the
      specificity of the criteria.

PMID- 24297385
TI  - Cell death proteins as markers of early postmortem interval.
AB  - Estimation of time since death is one of the challenges in forensic science.
      There are many approaches to estimate the postmortem interval, including both
      physical and thanatochemistry methods. Decomposition is triggered by a process
      called autolysis, which induces destructive changes in the cell leading to cell
      death. Based on the process of cell death signaling, this study analyzed the
      early postmortem interval (2-8 h since death) using the study of the mRNA
      expression of Fas Ligand (FasL) and phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN) by Quantitative-PCR. Results of the study indicate a time
      dependent increase in the mRNA levels of both proteins up until 6 h after death.
      Using a regression analysis in these first 6 h, a positive linear correlation was
      found between the mRNA expression of these proteins and the time since death.
      Since PTEN and FasL are implicated in signaling pathways, both proteins are
      potential candidates to analyze the time since death in time intervals of 6 h or
      less. Further research is needed to find additional cell death markers and expand
      the time period for time since death estimation.

PMID- 24297386
TI  - Function of inducible nitric oxide synthase in the regulation of cervical cancer
      cell proliferation and the expression of vascular endothelial growth factor.
AB  - Inducible nitric oxide synthase (iNOS) is the key enzyme in NO synthesis and
      exhibits a high expression in numerous types of malignant tumors. Previous
      studies have demonstrated that iNOS promotes the production of tumor blood
      vessels by catalyzing the synthesis of additional NO. Certain experimental
      evidence has suggested that iNOS may regulate the levels of vascular endothelial
      growth factor (VEGF), as the level of VEGF may be induced by iNOS during
      endothelial cell migration and angiogenesis. In this study, it was observed that
      SiHa and HeLa cells exhibit depressed proliferation levels following the
      knockdown of iNOS with a lentivirus. In addition, NO levels demonstrated a
      correlation with VEGF levels in the cell culture supernatant.

PMID- 24297387
TI  - (89)Sr bremsstrahlung single photon emission computed tomography using a gamma
      camera for bone metastases.
AB  - OBJECTIVE: Strontium-89 chloride ((89)Sr) bremsstrahlung single photon emission
      computed tomography (SPECT) imaging was evaluated for detecting more detailed
      whole body (89)Sr distribution. METHODS: (89)Sr bremsstrahlung whole body planar
      and merged SPECT images were acquired using two-detector SPECT system. Energy
      window A (100 keV +/- 50 %) for planar imaging and energy window A plus adjacent
      energy window B (300 keV +/- 50 %) for SPECT imaging were set on the continuous
      spectrum. Thirteen patients with multiple bone metastases were evaluated. Bone
      metastases can be detected with (99m)Tc-HMDP whole body planar and merged SPECT
      images and compared with (89)Sr bremsstrahlung whole body planar and merged SPECT
      images. Based on the location of metastatic lesions seen as hot spots on (99m)Tc
      HMDP images as a reference, the hot spots on (89)Sr bremsstrahlung images were
      divided into the same bone parts as (99m)Tc-HMDP images (a total of 35 parts in
      the whole body), and the number of hot spots were counted. We also evaluated the
      incidence of extra-osseous uptakes in the intestine on (89)Sr bremsstrahlung
      whole body planar images. RESULTS: A total of 195 bone metastatic lesions were
      detected in both (99m)Tc-HMDP whole body planar and merged SPECT images.
      Detection of hot spot lesions in (89)Sr merged SPECT images (127 of 195; 66 %)
      was more frequent than in (89)Sr whole body planar images (108 of 195; 56 %),
      based on metastatic bone lesions in (99m)Tc-HMDP whole body planar and merged
      SPECT images. A large intestinal (89)Sr accumulation was detected in 5 of the 13
      patients (38 %). CONCLUSIONS: (89)Sr bremsstrahlung-merged SPECT imaging could be
      more useful for detailed detection of whole body (89)Sr distribution than planar
      imaging. Intestinal (89)Sr accumulation due to (89)Sr physiologic excretion was
      detected in feces for 4 days after tracer injection.

PMID- 24297388
TI  - Metabolic information on staging FDG-PET-CT as a prognostic tool in the
      evaluation of 97 patients with gastric cancer.
AB  - BACKGROUND AND OBJECTIVE: Gastric cancer remains a leading cause of malignancy
      related mortality. Many patients with locally advanced disease succumb despite
      peri-operative chemotherapy and the survival benefit of chemotherapy for advanced
      disease is modest, suggesting that current staging is imperfect. The role of
      fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in
      the staging of gastric cancer remains to be determined. This study aimed to
      determine, and compare with computerized tomography (CT), the association between
      FDG-PET uptake in the primary tumour and regional lymph nodes, and overall
      survival in patients with all stage gastric cancer. METHODS: Patients with
      histologically confirmed gastric cancer (any stage) who, at diagnosis, had
      received a staging FDG-PET-CT at our institution between 2006 and 2011 were
      included. Records were retrospectively analysed. Patients with >50 % of tumour
      above the gastro-oesophageal junction or an active second malignancy were
      excluded. RESULTS: 97 patients were included in the analysis. Surgery with
      curative intent was performed in 68 patients. In univariate analysis, an
      association with overall survival was seen in patients who had FDG-PET-positive
      primary tumours (hazard ratio (HR) for death 3.33, 95 % confidence interval (95 %
      CI) 1.63-6.80, p = 0.001). FDG-PET lymph node positive (vs node negativity) was
      associated with inferior overall survival (HR 8.66, 95 % CI 4.59-16.37, p <
      0.0001), and remained an independent predictor in the multivariate analysis. In
      contrast, positive lymphadenopathy identified on CT was not associated with
      overall survival (HR 1.34, 95 % CI 0.79-2.29, p = 0.82). CONCLUSION: FDG-PET
      positive tumours are associated with an inferior overall survival. In contrast to
      CT, FDG-PET-positive lymphadenopathy is associated with a decreased overall
      survival.

PMID- 24297389
TI  - Antibiotics for preterm rupture of membranes.
AB  - BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality.
      Subclinical infection is associated with preterm rupture of membranes (PROM).
      Prophylactic maternal antibiotic therapy might lessen infectious morbidity and
      delay labour, but could suppress labour without treating underlying infection.
      OBJECTIVES: To evaluate the immediate and long-term effects of administering
      antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity,
      neonatal morbidity and mortality, and longer-term childhood development. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 September 2013). SELECTION CRITERIA: Randomised controlled trials
      comparing antibiotic administration with placebo that reported clinically
      relevant outcomes were included as were trials of different antibiotics. Trials
      in which no placebo was used were included for the outcome of perinatal death
      alone. DATA COLLECTION AND ANALYSIS: We extracted data from each report without
      blinding of either the results or the treatments that women received. We sought
      unpublished data from a number of authors. MAIN RESULTS: We included 22 trials,
      involving 6872 women and babies.The use of antibiotics following PROM is
      associated with statistically significant reductions in chorioamnionitis (average
      risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction
      in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to
      0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The
      following markers of neonatal morbidity were reduced: neonatal infection (RR
      0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96),
      oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound
      scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co
      amoxiclav was associated with an increased risk of neonatal necrotising
      enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's
      health at seven years of age (ORACLE Children Study) and found antibiotics seemed
      to have little effect on the health of children. AUTHORS' CONCLUSIONS: Routine
      prescription of antibiotics for women with preterm rupture of the membranes is
      associated with prolongation of pregnancy and improvements in a number of short
      term neonatal morbidities, but no significant reduction in perinatal mortality.
      Despite lack of evidence of longer-term benefit in childhood, the advantages on
      short-term morbidities are such that we would recommend antibiotics are routinely
      prescribed. The antibiotic of choice is not clear but co-amoxiclav should be
      avoided in women due to increased risk of neonatal necrotising enterocolitis.

PMID- 24297390
TI  - Regression of choroidal hemangioma following systemic paclitaxel and trastuzumab
      use.

PMID- 24297393
TI  - Biomarker investigations in adult female perch (Perca fluviatilis) from
      industrialised areas in northern Sweden in 2003.
AB  - Since the new millennium, a notion has developed in certain parts of society that
      environmental pollutants and their associated effects are under control. The
      primary objective of this investigation, performed in 2003, was to test whether
      this was actually the case in an industrialised region in the County of
      Vasternorrland in northern Sweden with well-documented environmental pollution
      from past and present activities. This was performed by measuring a moderate
      battery of simple biomarkers in adult female perch at several stations. The point
      sources included sewage-treatment plants, pulp and paper mills, as well as other
      industries. The biomarkers included growth, somatic indices, gonad maturation
      status, gonad pigmentation, fin erosion, skin ulcers, and ethoxyresorufin-O
      deethylase (EROD) activity in the liver. The results showed that the
      environmental pollutants and their associated effects were not under control. In
      fact, the health of the perch was impaired at all of the polluted stations. Many
      responses were unspecific with respect to underlying cause, whereas some effects
      on EROD activity and gonad maturation status were attributed to historical
      creosote pollution and current kraft pulp mill effluents, respectively. The data
      presented may also be used as reference values for future investigations of
      health effects in perch. 

PMID- 24297392
TI  - Sialic acid-binding lectin (leczyme) induces apoptosis to malignant mesothelioma
      and exerts synergistic antitumor effects with TRAIL.
AB  - Malignant mesothelioma is a highly aggressive tumor with poor prognosis. An
      effective drug for treatment of malignant mesothelioma is greatly needed. Sialic
      acid-binding lectin (SBL) isolated from oocytes of Rana catesbeiana is a
      multifunctional protein which has lectin activity, ribonuclease activity and
      antitumor activity, so it could be developed as a new type of anticancer drug.
      The validity of SBL for treatment of malignant mesothelioma was assessed using
      three malignant mesotheliomas and a non-malignant mesothlial cell line.
      Effectiveness of combinatorial treatment of SBL and tumor necrosis factor-related
      apoptosis inducing ligand (TRAIL) was also elucidated and characterized. SBL
      induced tumor-selective cytotoxicity that was attributed to induction of
      apoptosis. Combinatorial treatment of SBL and TRAIL showed synergistic apoptosis
      inducing effect. Additional experiments revealed that Bid was the mediating
      molecule for the synergistic effect in SBL and TRAIL. These results suggested
      that SBL could be a promising candidate for the therapeutics for malignant
      mesothelioma. Furthermore, the combinatorial treatment of SBL and TRAIL could be
      an effective regimen against malignant mesothelioma. 

PMID- 24297394
TI  - Difference in LDL receptor feedback regulation in macrophages and vascular smooth
      muscle cells: foam cell transformation under inflammatory stress.
AB  - Macrophages and vascular smooth muscle cells (VSMCs) are the major cell types
      involved in foam cell formation associated with atherosclerosis. The aim of this
      experiment was to clarify cell-specific regulation of LDL receptor in THP-1
      macrophages and human VSMCs under physiological and inflammatory conditions and
      its potential mechanisms. Inflammatory stress was induced by adding
      lipopolysaccharide (LPS) to human THP-1 macrophages and human VSMCs.
      Intracellular total cholesterol, free cholesterol, and cholesterol ester were
      measured by an enzymic assay. Oil Red O staining was used to visualize lipid
      droplet accumulation in cells. Total cellular RNA was isolated from cells for
      detecting LDL receptor, sterol regulatory element binding protein (SREBP)-2 and
      SREBP cleavage-activating protein (SCAP) mRNA levels using real-time quantitative
      polymerase chain reaction. LDL receptor, SREBP-2 and SCAP protein expression were
      examined by Western blotting. The translocation of SCAP from ER to Golgi was
      detected by confocal microscopy. LDL loading increased intracellular cholesterol
      level, reducing LDL receptor mRNA level in both THP-1 macrophages and VSMCs under
      physiological conditions. The IC50 in VSMCs was 11.25 MUg/ml, which is much lower
      than 18.125 MUg/ml in THP-1 macrophages. With the increase in concentration of
      LPS (0-400 ng/ml), the LDL receptor mRNA levels were upregulated in both cells,
      but the curve of LDL receptor mRNA in VSMCs exhibited a flatter profile than that
      of THP-1 macrophages. Under the treatment of 200 ng/ml of LPS, the upregulation
      fold of the LDL receptor mRNA in THP-1 macrophages was much higher than that of
      VSMCs (0.33 vs 0.04). LDL receptor blocking agent heparin decreased lipid
      droplets induced by LPS significantly in THP-1 macrophages and VSMCs. LDL loading
      reduced the SREBP2 and SCAP protein expression under physiological conditions.
      Exposure to LPS caused overexpression of SREBP2 and SCAP despite a high
      concentration of LDL in the culture medium, and increased translocation of SCAP
      from the ER to the Golgi in the presence of 25 MUg/ml of LDL. Inflammatory stress
      disrupts LDL receptor negative feedback regulation induced by intracellular
      cholesterol in both cell types, to a greater degree in THP-1 macrophages, which
      could be one reason why THP-1 macrophages are more prone to become foam cells
      under inflammatory stress.

PMID- 24297395
TI  - Transcatheter closure of a large fistula between the right pulmonary artery and
      left atrium. Use of a muscular ventricular septal occluder.

PMID- 24297396
TI  - Noninvasive fractional flow reserve measurement in stable CAD.

PMID- 24297397
TI  - Association of epicardial fat thickness with TIMI risk score.

PMID- 24297398
TI  - Phase-4 paroxysmal atrioventricular block in sarcoidosis.

PMID- 24297399
TI  - Retrieval of a malpositioned left subclavian artery stent from the ascending
      aorta: combined percutaneous and surgical management.
AB  - Chronic upper limb ischemia is an uncommon clinical condition and is most often
      caused by subclavian artery stenosis. Surgical and percutaneous treatment
      modalities have been shown to be effective for the management of subclavian
      artery occlusion. Because of lower mortality and morbidity rates, percutaneous
      interventions for subclavian arterial occlusions are more acceptable than
      surgery. Chronic total occlusions of the subclavian artery are challenging to
      treat percutaneously because of the structure and complexity of the lesion. The
      complexity of the lesion causes its own complications. In this paper, we report a
      case of a completely occluded left subclavian artery that was complicated by a
      malpositioned stent hanging into the aortic arch and the ascending aorta during
      percutaneous intervention, which was successfully managed by our heart team. 

PMID- 24297400
TI  - Blood cyst of the mitral valve in an adult.

PMID- 24297401
TI  - Absence of the right coronary artery with distal angulation of the left
      circumflex coronary artery.

PMID- 24297402
TI  - Coronary guidewire perforation into the left ventricular cavity: A rare
      complication of coronary angioplasty.

PMID- 24297403
TI  - Nonbacterial endocarditis presenting as a right ventricular tumor in assumed
      Behcet's disease.

PMID- 24297404
TI  - Diagnostic dilemma in pulmonary arterial hypertension: idiopathic or chronic
      thromboembolic hypertension?

PMID- 24297405
TI  - High-throughput synchronization of mammalian cell cultures by spiral
      microfluidics.
AB  - The development of mammalian cell cycle synchronization techniques has greatly
      advanced our understanding of many cellular regulatory events and mechanisms
      specific to different phases of the cell cycle. In this chapter, we describe a
      high-throughput microfluidic-based approach for cell cycle synchronization. By
      exploiting the relationship between cell size and its phase in the cell cycle,
      large numbers of synchronized cells can be obtained by size fractionation in a
      spiral microfluidic channel. Protocols for the synchronization of primary cells
      such as mesenchymal stem cells, and immortal cell lines such as Chinese hamster
      ovarian cells (CHO-CD36) and HeLa cells are provided as examples. 

PMID- 24297406
TI  - Insect cell line development using FLP-mediated cassette exchange technology.
AB  - Traditional cell line development is quite laborious and time-consuming as it is
      based on the random integration of the gene of interest which leads to
      unpredictable expression behavior. In opposition, recombinase-mediated cassette
      exchange systems represent a powerful genetic engineering approach, allowing site
      specific insertion of recombinant genes into pre-tagged genomic loci with
      superior expression characteristics, thus bypassing the need for extensive clone
      screening and shortening the development timelines. Such systems have not been
      widely implemented in insect cell lines used for the production of recombinant
      proteins most commonly through the baculovirus expression vector system. Herein,
      it is provided the protocol for the implementation of a FLP-mediated cassette
      exchange system in Spodoptera frugiperda Sf 9 cells, in order to grant a flexible
      cell line for the stable production of recombinant proteins. 

PMID- 24297407
TI  - Scalable transient gene expression in adherent mammalian cells using
      polyethylenimine.
AB  - Transient gene expression (TGE) has become a powerful tool over the last decade,
      as time to market is a key factor in biopharmaceutical industry. TGE is used to
      produce small amounts of recombinant protein for functional and structural
      studies. To broaden the applicability of the method, the scale-up of TGE has been
      in scope of the scientific community over the last decade. Culture volumes of up
      to 100 l have been transfected, but there are still bottlenecks regarding the
      compatibility of the transfection method and media composition as well as media
      exchange or dilution required after transfection. Cell immobilization on
      microcarriers is a scalable option to circumvent cell concentration by
      centrifugation and subsequent dilution or perfusion. Furthermore microcarrier
      based cultivation offers a simple solution for medium exchange which allows to
      maintain cultures during a production period of several weeks. 

PMID- 24297408
TI  - Scalable transient protein expression.
AB  - Transient transfection is a well-established method to rapidly express
      recombinant proteins from mammalian cells. Accelerating activity in
      biotherapeutic drug development, demand for protein-based reagents, vaccine
      research, and large initiatives in structural and functional studies of proteins
      have propelled the need to generate moderate to high amounts of recombinant
      proteins and other macromolecules in a flexible and rapid manner. Progress over
      the last 10-15 years has demonstrated that transient transfections can be
      reliably and readily scaled up to handle milliliters to tens of liters of cells
      in suspension culture and obtain milligrams to grams of recombinant protein in a
      process that requires only days to weeks. This review will summarize developments
      in this field, properties of the components of a transient expression system that
      enable maximal protein production, and detailed protocols for this application. 

PMID- 24297409
TI  - DNA profiling and characterization of animal cell lines.
AB  - The history of the culture of animal cell lines is littered with published and
      much unpublished experience with cell lines that have become switched,
      mislabelled, or cross-contaminated during laboratory handling. To deliver valid
      and good quality research and to avoid waste of time and resources on such rogue
      lines, it is vital to perform some kind of qualification for the provenance of
      cell lines used in research and particularly in the development of biomedical
      products. DNA profiling provides a valuable tool to compare different sources of
      the same cells and, where original material or tissue is available, to confirm
      the correct identity of a cell line. This chapter provides a review of some of
      the most useful techniques to test the identity of cells in the cell culture
      laboratory and gives methods which have been used in the authentication of cell
      lines. 

PMID- 24297410
TI  - Tools for high-throughput process and medium optimization.
AB  - Shaking technology in combination with small-scale disposable plastic vessels has
      become a notable bioprocess optimization tool widely exploited for cells grown in
      suspension. This chapter focuses on the two most accommodating culture systems:
      50 mL centrifugation tubes and 96-deepwell plates. Used by many laboratories for
      routine passaging of suspension cultures and all types of optimization
      experiments as flexible culture system, the 50 mL shake tubes are the preferred
      vessels for manual manipulations, while microtiter plates are the ideal
      containers when automatic liquid handling systems are available. Both culture
      systems can offer to the cells a well-mixed environment which is close to the
      conditions found at larger scale in production bioreactors. 

PMID- 24297411
TI  - Designing media for animal cell culture: CHO cells, the industrial standard.
AB  - The success of culturing CHO cells solely depends on functionality of the used
      media. Cell culture technology is more than 50 years old, and the knowledge of
      cell requirements increased steadily. In the beginning, animal-sourced components
      were the key to growth. Nowadays state-of-the-art media do not contain any animal
      or naturally sourced components. The compositions are based on scientific
      awareness of the needs of the cells. The result is high lot-to-lot consistency
      and high performance.In this book section, a method for the development of a
      synthetic, animal component-free medium is described. The composition is based on
      public available formulations and information based on the work of many
      scientists printed in numerous papers and manuscripts. The method shall help
      beginners to design their own medium, although some knowledge of biochemistry and
      animal cells is still required. 

PMID- 24297413
TI  - Screening and optimization of chemically defined media and feeds with integrated
      and statistical approaches.
AB  - The majority of therapeutic proteins are expressed in mammalian cells,
      predominantly in Chinese Hamster Ovary cells. While cell culture media and feed
      supplements are crucial to protein productivity, medium optimization can be labor
      intensive and time-consuming. In this chapter, we describe some basic concepts in
      medium development and introduce a rational and rapid workflow to screen and
      optimize media and feeds. The major goal of medium screening is to select a base
      formulation as the foundation for further optimization, but ironically, the most
      conventional screening method may actually rule out ideal chemically defined
      medium candidates. Appropriate cell adaptation is the key to identifying an
      optimal base medium, particularly when cells were originally cultured in serum
      free medium containing recombinant proteins and/or undefined hydrolysates. The
      efficient workflow described herein integrates the optimization of both medium
      and feed simultaneously using a Design-of-Experiment (DOE) approach. The
      feasibility of the workflow is then demonstrated with a case study, in which
      chemically defined medium and feed were optimized in a single fed-batch study
      using a high-throughput microbioreactor system (SimCellTM), which resulted in
      improving protein titers three- to sixfold.

PMID- 24297412
TI  - Feed optimization in fed-batch culture.
AB  - Fed-batch processes are a current preference for the production of recombinant
      proteins in mammalian cells. The use of nutrient feeding prevents the depletion
      of important medium components and results in improved culture longevity and high
      cell and product yields. To take maximum advantage of these effects, it is
      important to optimize the fed-batch process for each application. In this
      chapter, a simple strategy for fed-batch optimization is described, consisting of
      the development of a feed medium based on spent media analysis and the
      establishment of a feeding strategy that consists of adding variable volumes of
      feed media at specific intervals, after off-line measurement of the concentration
      of a reference nutrient. 

PMID- 24297414
TI  - Evaluation of solid and porous microcarriers for cell growth and production of
      recombinant proteins.
AB  - Microcarrier technology opened new perspectives for anchorage-dependent cell
      culture, by providing increased surface areas for cell adhesion and
      proliferation, and therefore improving both cell and product yields obtained in
      these cultures. The establishment of a successful microcarrier culture depends on
      many factors, such as the type of microcarrier, the cells, and the culture
      conditions. In this chapter, the basic steps required for the evaluation and
      optimization of a microcarrier culture for the purpose of production of
      recombinant proteins are described, for both solid and porous microcarriers. 

PMID- 24297415
TI  - Microbioreactors and scale-down models: growth of CHO cells using the Pall
      Micro24 MicroReactor system.
AB  - Microbioreactors are increasingly used within animal cell biotechnology to grow
      mammalian cells for cell line screening and to facilitate process development.
      Many such devices have been reported in the literature, but only a small number
      are available commercially. Microbioreactors range in complexity from simple
      plate-based systems to complex automated parallel bioreactors designed to enable
      the meaningful scale-down of conventional bioprocesses. The Micro24 MicroReactor
      system (Pall Life Sciences) fits between these extremes providing 24* 7 mL
      parallel "bioreactors" with individual monitoring and control of temperature, pH,
      and dissolved oxygen. Inoculation, sampling, and feed additions are carried out
      manually in a Biological Safety Cabinet. In this chapter we describe the use of
      the Micro24 system to carry out screening or process development experiments with
      CHO cells.

PMID- 24297416
TI  - Monitoring cell growth, viability, and apoptosis.
AB  - The accurate determination of cell growth and viability is pivotal to monitoring
      a bioprocess. Direct methods to determine the cell growth and/or viability in a
      bioprocess include microscopic counting, electronic particle counting, image
      analysis, in situ biomass monitoring, and dieletrophoretic cytometry. These
      methods work most simply when a fixed volume sample can be taken from a
      suspension culture. Manual microscopic counting is laborious but affords the
      advantage of allowing cell viability to be determined if a suitable dye is
      included. Electronic particle counting is a rapid total cell count method for
      replicate samples, but some data distortion may occur if the sample has
      significant cell debris or cell aggregates. Image analysis based on the use of
      digital camera images acquired through a microscope has advanced rapidly with the
      availability of several commercially available software packages replacing manual
      microscopic counting and viability determination. Biomass probes detect cells by
      their dielectric properties or their internal concentration of NADH and can be
      used as a continuous monitor of the progress of a culture. While the monitoring
      of cell growth and viability is an integral part of a bioprocess, the monitoring
      of apoptosis induction is also becoming more and more important in bioprocess
      control to increase volumetric productivity by extending bioprocess duration.
      Different fluorescent assays allow for the detection of apoptotic characteristics
      in a cell sample.Indirect methods of cell determination involve the chemical
      analysis of a culture component or a measure of metabolic activity. These methods
      are most useful when it is difficult to obtain intact cell samples. However, the
      relationship between these parameters and the cell number may not be linear
      through the phases of a cell culture. The determination of nucleic acid (DNA) or
      total protein can be used as an estimate of biomass, while the depletion of
      glucose from the media can be used as an estimate of cellular activity. The state
      of cellular viability may be measured by the release of an enzyme such as lactate
      dehydrogenase or more directly from the intracellular adenylate energy charge
      from cell lysates. Alternatively, radioactive techniques may be used for an
      accurate determination of cellular protein synthesis.

PMID- 24297417
TI  - Metabolic flux estimation in mammalian cell cultures.
AB  - Metabolic flux analysis with its ability to quantify cellular metabolism is an
      attractive tool for accelerating cell line selection, medium optimization, and
      other bioprocess development activities. In the stoichiometric flux estimation
      approach, unknown fluxes are determined using intracellular metabolite mass
      balance expressions and measured extracellular rates. The simplicity of the
      stoichiometric approach extends its application to most cell culture systems, and
      the steps involved in metabolic flux estimation by the stoichiometric method are
      presented in detail in this chapter. Specifically, overdetermined systems are
      analyzed since the extra measurements can be used to check for gross measurement
      errors and system consistency. Cell-specific rates comprise the input data for
      flux estimation, and the logistic modeling approach is described for robust
      specific rate estimation in batch and fed-batch systems. A simplified network of
      mammalian cell metabolism is used to illustrate the flux estimation procedure,
      and the steps leading up the consistency index determination are presented. If
      gross measurement errors are detected, a technique for determining the source of
      gross measurement error is also described. A computer program that performs most
      of the calculation described in this chapter is presented, and references to flux
      estimation software are provided. The procedure presented in this chapter should
      enable rapid metabolic flux estimation in any mammalian cell bioreaction network
      by the stoichiometric approach. 

PMID- 24297418
TI  - Quenching methods for the analysis of intracellular metabolites.
AB  - Sampling and quenching methods for intracellular metabolite analysis in mammalian
      cells in adherent and suspension culture are described. Quenching of adherent
      cells is achieved by application of hot air after removal of the supernatant by
      suction. For suspension cultures, the addition of excess ice-cold saline results
      in a rapid inactivation of metabolism and significant dilution of extracellular
      metabolites. Medium carryover is prevented by rinsing the cells with washing
      solution. Separation of supernatant from suspension cells via centrifugation is
      incomplete due to required short centrifugation time. Thus, it is necessary to
      determine the reproducible cell recovery after quenching. 

PMID- 24297419
TI  - NMR methods for metabolomics of mammalian cell culture bioreactors.
AB  - Metabolomics has become an important tool for measuring pools of small molecules
      in mammalian cell cultures expressing therapeutic proteins. NMR spectroscopy has
      played an important role, largely because it requires minimal sample preparation,
      does not require chromatographic separation, and is quantitative. The
      concentrations of large numbers of small molecules in the extracellular media or
      within the cells themselves can be measured directly on the culture supernatant
      and on the supernatant of the lysed cells, respectively, and correlated with
      endpoints such as titer, cell viability, or glycosylation patterns. The observed
      changes can be used to generate hypotheses by which these parameters can be
      optimized. This chapter focuses on the sample preparation, data acquisition, and
      analysis to get the most out of NMR metabolomics data from CHO cell cultures but
      could easily be extended to other in vitro culture systems. 

PMID- 24297420
TI  - 1H-NMR protocol for exometabolome analysis of cultured mammalian cells.
AB  - (1)H-Nuclear magnetic resonance ((1)H-NMR) spectroscopy is a powerful technique
      to analyze the composition of complex mixtures based on the particular proton
      fingerprint of each molecule. Here we describe a protocol for exometabolome
      analysis of mammalian cells using this technique, including sample preparation,
      spectra acquisition, and integration. The potential of this technique is
      exemplified by application to cultures of a Chinese hamster ovary (CHO) cell
      line. The average error associated to this method is under 3% and the limit of
      quantification for all metabolites analyzed is below 180 MUM.

PMID- 24297421
TI  - Microfluidic perfusion culture.
AB  - Microfluidic perfusion culture is a novel technique to culture animal cells in a
      small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is
      the most popular material to fabricate a microfluidic perfusion culture chip.
      Photolithography and replica molding techniques are generally used for
      fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion
      culture system is convenient technique to carry out the perfusion culture of
      animal cells in a microfluidic device. Here, we describe a general theory on
      microfluid network design, microfabrication technique, and experimental technique
      for pressure-driven perfusion culture in an 8 * 8 microchamber array on a glass
      slide-sized microchip made out of PDMS. 

PMID- 24297422
TI  - Disposable bioreactors for inoculum production and protein expression.
AB  - Disposable bioreactors have been increasingly implemented over the past ten
      years. This relates to both R & D and commercial manufacture, in particular, in
      animal cell-based processes. Among the numerous disposable bioreactors which are
      available today, wave-mixed bag bioreactors and stirred bioreactors are
      predominant. Whereas wave-mixed bag bioreactors represent the system of choice
      for inoculum production, stirred systems are often preferred for protein
      expression. For this reason, the authors present protocols instructing the reader
      how to use the wave-mixed BIOSTAT CultiBag RM 20 L for inoculum production and
      the stirred UniVessel SU 2 L for recombinant protein production at benchtop
      scale. All methods described are based on a Chinese hamster ovary (CHO)
      suspension cell line expressing the human placental secreted alkaline phosphatase
      (SEAP). 

PMID- 24297423
TI  - Configuration of bioreactors.
AB  - Lab-scale stirred-tank bioreactors (0.2-20 l) are used for fundamental research
      on animal cells and in process development and troubleshooting for large-scale
      production. In this chapter, different configurations of bioreactor systems are
      shortly discussed and setting up these different configurations is described. In
      addition, online measurement and control of bioreactor parameters is described,
      with special attention to controller settings (PID) and online measurement of
      oxygen consumption and carbon dioxide production. Finally, methods for
      determining the oxygen transfer coefficient are described. 

PMID- 24297424
TI  - Process analytical technology (PAT) in insect and mammalian cell culture
      processes: dielectric spectroscopy and focused beam reflectance measurement
      (FBRM).
AB  - Modern bioprocesses demand for a careful definition of the critical process
      parameters (CPPs) already during the early stages of process development in order
      to ensure high-quality products and satisfactory yields. In this context, online
      monitoring tools can be applied to recognize unfavorable changes of CPPs during
      the production processes and to allow for early interventions in order to prevent
      losses of production batches due to quality issues. Process analytical
      technologies such as the dielectric spectroscopy or focused beam reflectance
      measurement (FBRM) are possible online monitoring tools, which can be applied to
      monitor cell growth as well as morphological changes. Since the dielectric
      spectroscopy only captures cells with intact cell membranes, even information
      about dead cells with ruptured or leaking cell membranes can be derived. The
      following chapter describes the application of dielectric spectroscopy on various
      virus-infected and non-infected cell lines with respect to adherent as well as
      suspension cultures in common stirred tank reactors. The adherent mammalian cell
      lines Vero (African green monkey kidney cells) and hMSC-TERT (telomerase
      immortalized human mesenchymal stem cells) are thereby cultured on microcarrier,
      which provide the required growth surface and allow the cultivation of these
      cells even in dynamic culture systems. In turn, the insect-derived cell lines S2
      and Sf21 are used as examples for cells typically cultured in suspension.
      Moreover, the FBRM technology as a further monitoring tool for cell culture
      applications has been included in this chapter using the example of Drosophila S2
      insect cells. 

PMID- 24297425
TI  - Cell assessment by at-line microscopy.
AB  - This protocol regards a microscopic application and software for image-guided
      monitoring of mammalian cells which grow in suspension cultures. It has been
      developed in order to establish an automated microscopic application for in situ
      and at-line cell monitoring in bioreactors (Akin et al., Biosens Bioelectron
      26:4532-4537, 2011; Babitzky et al., At-line microscopic analysis of suspension
      cell cultures. In: ECCE/ECAB, the first joint European Congress of chemical
      engineering and applied biotechnology, September 25-29, 2011, Berlin, Germany,
      2011. http://www.tci.uni-hannover.de, Poster). The application aims to assess the
      analysis of an appropriated sample volume of mammalian cell cultivation medium.
      The sample is injected into a microfluidic slide which is suitable for
      transmitted light microscopy and is attached to an automated microscope device,
      the at-line microscope. The major attribute of microscope automation ascribes to
      the camera software, which enables sequential image capturing and storing. Image
      analysis and cell detection are performed by the software that is based on the
      edge detection algorithm developed by Canny (IEEE Trans Pattern Anal Mach Intell
      8:679-698, 1986; Finding edges and lines in images.Technical Report 720, MIT
      Artificial Intelligence Laboratory, 1983). The analysis results are cell count,
      morphological characteristics, and grayscale values of the detected cells. The
      presented setup can be applied to low-volume cultivations and has been
      successfully tested for monitoring CHO-K1 cell cultivation processes.

PMID- 24297426
TI  - Seed train optimization for cell culture.
AB  - For the production of biopharmaceuticals a seed train is required to generate an
      adequate number of cells for inoculation of the production bioreactor. This seed
      train is time- and cost-intensive but offers potential for optimization. A method
      and a protocol are described for the seed train mapping, directed modeling
      without major effort, and its optimization regarding selected optimization
      criteria such as optimal points in time for cell passaging. Furthermore, the
      method can also be applied for the set-up of a new seed train, for example for a
      new cell line. Although the chapter is directed towards suspension cell lines,
      the method is also generally applicable, e.g. for adherent cell lines. 

PMID- 24297427
TI  - Vaccine production: upstream processing with adherent or suspension cell lines.
AB  - The production of viral vaccines in cell culture can be accomplished with
      primary, diploid, or continuous (transformed) cell lines. Each cell line, each
      virus type, and each vaccine preparation require the specific design of upstream
      and downstream processing. Media have to be selected as well as production
      vessels, cultivation conditions, and modes of operation. Many viruses only
      replicate to high titers in adherently growing cells, but similar to processes
      established for recombinant protein production, an increasing number of
      suspension cell lines is being evaluated for future use. Here, we describe key
      issues to be considered for the establishment of large-scale virus production in
      bioreactors. As an example upstream processing of cell culture-derived influenza
      virus production is described in more detail for adherently growing and for
      suspension cells. In particular, use of serum-containing, serum-free, and
      chemically defined media as well as choice of cultivation vessel are considered. 

PMID- 24297428
TI  - Efficient processes for protein expression using recombinant baculovirus
      particles.
AB  - The use of baculoviruses has become a standard approach in many labs for
      recombinant protein production. In addition to giving a broad and practical
      overview of the technology, this chapter focuses in particular on two recent
      developments in the field and how these can be efficiently exploited for protein
      production: the use of baculovirus-infected insect cells and in vivo
      recombination-mediated production of recombinant viruses. 

PMID- 24297429
TI  - Chromatographic techniques in the downstream processing of proteins in
      biotechnology.
AB  - The purification of the product, the so-called downstream process (DSP), tends to
      be one of the most costly aspects of modern bioprocessing, especially in the case
      of proteins. In such cases, chromatography is still the major tool on all levels
      of the DSP from the first capture to the final polishing step. In this chapter,
      we will first outline the commonly used methods and their setup, in particular
      ion exchange chromatography (IEX), hydrophobic interaction chromatography (HIC),
      affinity chromatography (AC), and gel filtration (GPC, SEC), but also some less
      known alternatives such as hydroxyapatite chromatography (HAC). Then the rational
      design of a downstream process, which usually comprises three orthogonal
      chromatographic steps, is discussed. Finally, process variants deviating from the
      usual batch-column/gradient elution approach will be presented, including
      expanded bed, displacement, and continuous chromatography, but also affinity
      precipitation. A most recent trend observable in the biotechnical DSP is the
      drive towards disposable elements (single-use technologies). Some options for
      this will be discussed as well. 

PMID- 24297430
TI  - Virus separation using membranes.
AB  - Industrial manufacturing of cell culture-derived viruses or virus-like particles
      for gene therapy or vaccine production are complex multistep processes. In
      addition to the bioreactor, such processes require a multitude of downstream unit
      operations for product separation, concentration, or purification. Similarly,
      before a biopharmaceutical product can enter the market, removal or inactivation
      of potential viral contamination has to be demonstrated. Given the complexity of
      biological solutions and the high standards on composition and purity of
      biopharmaceuticals, downstream processing is the bottleneck in many
      biotechnological production trains. Membrane-based filtration can be an
      economically attractive and efficient technology for virus separation. Viral
      clearance, for instance, of up to seven orders of magnitude has been reported for
      state of the art polymeric membranes under best conditions.This chapter
      summarizes the fundamentals of virus ultrafiltration, diafiltration, or
      purification with adsorptive membranes. In lieu of an impractical universally
      applicable protocol for virus filtration, application of these principles is
      demonstrated with two examples. The chapter provides detailed methods for
      production, concentration, purification, and removal of a rod-shaped baculovirus
      (Autographa californica M nucleopolyhedrovirus, about 40 * 300 nm in size, a
      potential vector for gene therapy, and an industrially important protein
      expression system) or a spherical parvovirus (minute virus of mice, 22-26 nm in
      size, a model virus for virus clearance validation studies). 

PMID- 24297431
TI  - Is Tachosil mesh better than polypropylene mesh for inguinal hernia repair?

PMID- 24297432
TI  - Well-differentiated pancreatic ductal adenocarcinomas measuring <= 1 cm exhibit
      early features of tumor progression: a report of five lesions and a comparative
      study with advanced lesions.
AB  - PURPOSE: The purpose of this study was to clarify whether the features of well
      differentiated pancreatic ductal adenocarcinomas (PDACs) measuring <= 1 cm are
      the same as those of early PDACs. METHODS: Five well-differentiated PDACs
      measuring <= 1 cm were clinicopathologically compared with 19 >= 2 cm PDACs.
      Additionally, an immunohistochemical analysis for abnormalities in the expression
      of five molecular parameters: MUC1, p16, p53, Smad4 and sonic hedgehog, which are
      associated with tumor progression, was performed. RESULTS: The
      clinicopathological comparison revealed that well-differentiated PDACs measuring
      <= 1 cm were detected significantly more often without angiolymphatic invasion
      and with a sparse presence of cancer cells than were the >= 2 cm PDACs. On the
      other hand, in well-differentiated PDACs measuring <= 1 cm, the incidence of
      abnormal immunolabeling for MUC1, p16, p53 and sonic hedgehog was similar to that
      in >= 2 cm PDACs. However, the incidence of diffusely positive immunolabeling for
      MUC1 and the mean number of abnormally immunolabeled samples for the five
      parameters were significantly lower in well-differentiated <= 1 cm PDACs (20 %
      and 3 +/- 1) than in >= 2 cm PDACs (90 % and 4 +/- 1). CONCLUSION: The current
      study revealed that as the tumor size increases, molecular abnormalities are
      accumulated, suggesting that well-differentiated PDACs measuring <= 1 cm are in
      an earlier stage of genetic progression than are >= 2 cm PDACs, and these lesions
      may exhibit early features of invasive PDACs.

PMID- 24297433
TI  - Immunosuppressive T-cell antibody induction for heart transplant recipients.
AB  - BACKGROUND: Heart transplantation has become a valuable and well-accepted
      treatment option for end-stage heart failure. Rejection of the transplanted heart
      by the recipient's body is a risk to the success of the procedure, and life-long
      immunosuppression is necessary to avoid this. Clear evidence is required to
      identify the best, safest and most effective immunosuppressive treatment strategy
      for heart transplant recipients. To date, there is no consensus on the use of
      immunosuppressive antibodies against T-cells for induction after heart
      transplantation. OBJECTIVES: To review the benefits, harms, feasibility and
      tolerability of immunosuppressive T-cell antibody induction versus placebo, or no
      antibody induction, or another kind of antibody induction for heart transplant
      recipients. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (Issue 11, 2012), MEDLINE (Ovid) (1946 to November
      Week 1 2012), EMBASE (Ovid) (1946 to 2012 Week 45), ISI Web of Science (14
      November 2012); we also searched two clinical trial registers and checked
      reference lists in November 2012. SELECTION CRITERIA: We included all randomised
      clinical trials (RCTs) assessing immunosuppressive T-cell antibody induction for
      heart transplant recipients. Within individual trials, we required all
      participants to receive the same maintenance immunosuppressive therapy. DATA
      COLLECTION AND ANALYSIS: Two authors extracted data independently. RevMan
      analysis was used for statistical analysis of dichotomous data with risk ratio
      (RR), and of continuous data with mean difference (MD), both with 95% confidence
      intervals (CI). Methodological components were used to assess risks of systematic
      errors (bias). Trial sequential analysis was used to assess the risks of random
      errors (play of chance). We assessed mortality, acute rejection, infection,
      Cytomegalovirus (CMV) infection, post-transplantation lymphoproliferative
      disorder, cancer, adverse events, chronic allograft vasculopathy, renal function,
      hypertension, diabetes mellitus, and hyperlipidaemia. MAIN RESULTS: In this
      review, we included 22 RCTs that investigated the use of T-cell antibody
      induction, with a total of 1427 heart-transplant recipients. All trials were
      judged to be at a high risk of bias. Five trials, with a total of 606
      participants, compared any kind of T-cell antibody induction versus no antibody
      induction; four trials, with a total of 576 participants, compared interleukin-2
      receptor antagonist (IL-2 RA) versus no induction; one trial, with 30
      participants, compared monoclonal antibody (other than IL-2 RA) versus no
      antibody induction; two trials, with a total of 159 participants, compared IL-2
      RA versus monoclonal antibody (other than IL-2 RA) induction; four trials, with a
      total of 185 participants, compared IL-2 RA versus polyclonal antibody induction;
      seven trials, with a total of 315 participants, compared monoclonal antibody
      (other than IL-2 RA) versus polyclonal antibody induction; and four trials, with
      a total of 162 participants, compared polyclonal antibody induction versus
      another kind, or dose of polyclonal antibodies.No significant differences were
      found for any of the comparisons for the outcomes of mortality, infection, CMV
      infection, post-transplantation lymphoproliferative disorder, cancer, adverse
      events, chronic allograft vasculopathy, renal function, hypertension, diabetes
      mellitus, or hyperlipidaemia. Acute rejection occurred significantly less
      frequently when IL-2 RA induction was compared with no induction (93/284 (33%)
      versus 132/292 (45%); RR 0.73; 95% CI 0.59 to 0.90; I(2) 57%) applying the fixed
      effect model. No significant difference was found when the random-effects model
      was applied (RR 0.73; 95% CI 0.46 to 1.17; I(2) 57%). In addition, acute
      rejection occurred more often statistically when IL-2 RA induction was compared
      with polyclonal antibody induction (24/90 (27%) versus 10/95 (11%); RR 2.43; 95%
      CI 1.01 to 5.86; I(2) 28%). For all of these differences in acute rejection,
      trial sequential alpha-spending boundaries were not crossed and the required
      information sizes were not reached when trial sequential analysis was performed,
      indicating that we cannot exclude random errors.We observed some occasional
      significant differences in adverse events in some of the comparisons, however
      definitions of adverse events varied between trials, and numbers of participants
      and events in these outcomes were too small to allow definitive conclusions to be
      drawn. AUTHORS' CONCLUSIONS: This review shows that acute rejection might be
      reduced by IL-2 RA compared with no induction, and by polyclonal antibody
      induction compared with IL-2 RA, though trial sequential analyses cannot exclude
      random errors, and the significance of our observations depended on the
      statistical model used. Furthermore, this review does not show other clear
      benefits or harms associated with the use of any kind of T-cell antibody
      induction compared with no induction, or when one type of T-cell antibody is
      compared with another type of antibody. The number of trials investigating the
      use of antibodies against T-cells for induction after heart transplantation is
      small, and the number of participants and outcomes in these RCTs is limited.
      Furthermore, the included trials are at a high risk of bias. Hence, more RCTs are
      needed to assess the benefits and harms of T-cell antibody induction for heart
      transplant recipients. Such trials ought to be conducted with low risks of
      systematic and random error.

PMID- 24297434
TI  - Consistency of nonparametric classification in cognitive diagnosis.
AB  - Latent class models for cognitive diagnosis have been developed to classify
      examinees into one of the 2 (K) attribute profiles arising from a K-dimensional
      vector of binary skill indicators. These models recognize that response patterns
      tend to deviate from the ideal responses that would arise if skills and items
      generated item responses through a purely deterministic conjunctive process. An
      alternative to employing these latent class models is to minimize the distance
      between observed item response patterns and ideal response patterns, in a
      nonparametric fashion that utilizes no stochastic terms for these deviations.
      Theorems are presented that show the consistency of this approach, when the true
      model is one of several common latent class models for cognitive diagnosis.
      Consistency of classification is independent of sample size, because no model
      parameters need to be estimated. Simultaneous consistency for a large group of
      subjects can also be shown given some conditions on how sample size and test
      length grow with one another. 

PMID- 24297435
TI  - A penalty approach to differential item functioning in Rasch models.
AB  - A new diagnostic tool for the identification of differential item functioning
      (DIF) is proposed. Classical approaches to DIF allow to consider only few
      subpopulations like ethnic groups when investigating if the solution of items
      depends on the membership to a subpopulation. We propose an explicit model for
      differential item functioning that includes a set of variables, containing metric
      as well as categorical components, as potential candidates for inducing DIF. The
      ability to include a set of covariates entails that the model contains a large
      number of parameters. Regularized estimators, in particular penalized maximum
      likelihood estimators, are used to solve the estimation problem and to identify
      the items that induce DIF. It is shown that the method is able to detect items
      with DIF. Simulations and two applications demonstrate the applicability of the
      method. 

PMID- 24297436
TI  - Hierarchical approximate Bayesian computation.
AB  - Approximate Bayesian computation (ABC) is a powerful technique for estimating the
      posterior distribution of a model's parameters. It is especially important when
      the model to be fit has no explicit likelihood function, which happens for
      computational (or simulation-based) models such as those that are popular in
      cognitive neuroscience and other areas in psychology. However, ABC is usually
      applied only to models with few parameters. Extending ABC to hierarchical models
      has been difficult because high-dimensional hierarchical models add computational
      complexity that conventional ABC cannot accommodate. In this paper, we summarize
      some current approaches for performing hierarchical ABC and introduce a new
      algorithm called Gibbs ABC. This new algorithm incorporates well-known Bayesian
      techniques to improve the accuracy and efficiency of the ABC approach for
      estimation of hierarchical models. We then use the Gibbs ABC algorithm to
      estimate the parameters of two models of signal detection, one with and one
      without a tractable likelihood function. 

PMID- 24297437
TI  - Factor copula models for item response data.
AB  - Factor or conditional independence models based on copulas are proposed for
      multivariate discrete data such as item responses. The factor copula models have
      interpretations of latent maxima/minima (in comparison with latent means) and can
      lead to more probability in the joint upper or lower tail compared with factor
      models based on the discretized multivariate normal distribution (or
      multidimensional normal ogive model). Details on maximum likelihood estimation of
      parameters for the factor copula model are given, as well as analysis of the
      behavior of the log-likelihood. Our general methodology is illustrated with
      several item response data sets, and it is shown that there is a substantial
      improvement on existing models both conceptually and in fit to data. 

PMID- 24297438
TI  - Modeling motivated misreports to sensitive survey questions.
AB  - Asking sensitive or personal questions in surveys or experimental studies can
      both lower response rates and increase item non-response and misreports. Although
      non-response is easily diagnosed, misreports are not. However, misreports cannot
      be ignored because they give rise to systematic bias. The purpose of this paper
      is to present a modeling approach that identifies misreports and corrects for
      them. Misreports are conceptualized as a motivated process under which
      respondents edit their answers before they report them. For example, systematic
      bias introduced by overreports of socially desirable behaviors or underreports of
      less socially desirable ones can be modeled, leading to more-valid inferences.
      The proposed approach is applied to a large-scale experimental study and shows
      that respondents who feel powerful tend to overclaim their knowledge. 

PMID- 24297439
TI  - Sck1 negatively regulates Gpa2-mediated glucose signaling in Schizosaccharomyces
      pombe.
AB  - Schizosaccharomyces pombe detects extracellular glucose via a G protein-mediated
      cyclic AMP (cAMP)-signaling pathway activating protein kinase A (PKA) and
      regulating transcription of genes involved in metabolism and sexual development.
      In this pathway, Gpa2 Galpha binds to and activates adenylyl cyclase in response
      to glucose detection by the Git3 G protein-coupled receptor. Using a two-hybrid
      screen to identify extrinsic regulators of Gpa2, we isolated a clone that
      expresses codons 471 to 696 of the Sck1 kinase, which appears to display a higher
      affinity for Gpa2(K270E)-activated Galpha relative to Gpa2(+) Galpha. Deletion of
      sck1(+) or mutational inactivation of the Sck1 kinase produces phenotypes
      reflecting increased PKA activity in strains expressing Gpa2(+) or Gpa2(K270E),
      suggesting that Sck1 negatively regulates PKA activation through Gpa2. In
      contrast to the Gpa2(K270E) GDP-GTP exchange rate mutant, GTPase-defective
      Gpa2(R176H) weakly binds Sck1 in the two-hybrid screen and a deletion of sck1(+)
      in a Gpa2(R176H) strain confers phenotypes consistent with a slight reduction in
      PKA activity. Finally, deleting sck1(+) in a gpa2Delta strain results in
      phenotypes consistent with a second role for Sck1 acting in parallel with PKA. In
      addition to this parallel role with PKA, our data suggest that Sck1 negatively
      regulates Gpa2, possibly targeting the nucleotide-free form of the protein that
      may expose the one and only AKT/PKB consensus site in Gpa2 for Sck1 to bind. This
      dual role for Sck1 may allow S. pombe to produce distinct biological responses to
      glucose and nitrogen starvation signals that both activate the Wis1-Spc1/StyI
      stress-activated protein kinase (SAPK) pathway. 

PMID- 24297440
TI  - Giardia intestinalis incorporates heme into cytosolic cytochrome b5.
AB  - The anaerobic intestinal pathogen Giardia intestinalis does not possess enzymes
      for heme synthesis, and it also lacks the typical set of hemoproteins that are
      involved in mitochondrial respiration and cellular oxygen stress management.
      Nevertheless, G. intestinalis may require heme for the function of particular
      hemoproteins, such as cytochrome b5 (cytb5). We have analyzed the sequences of
      eukaryotic cytb5 proteins and identified three distinct cytb5 groups: group I,
      which consists of C-tail membrane-anchored cytb5 proteins; group II, which
      includes soluble cytb5 proteins; and group III, which comprises the fungal cytb5
      proteins. The majority of eukaryotes possess both group I and II cytb5 proteins,
      whereas three Giardia paralogs belong to group II. We have identified a fourth
      Giardia cytb5 paralog (gCYTb5-IV) that is rather divergent and possesses an
      unusual 134-residue N-terminal extension. Recombinant Giardia cytb5 proteins,
      including gCYTb5-IV, were expressed in Escherichia coli and exhibited
      characteristic UV-visible spectra that corresponded to heme-loaded cytb5
      proteins. The expression of the recombinant gCYTb5-IV in G. intestinalis resulted
      in the increased import of extracellular heme and its incorporation into the
      protein, whereas this effect was not observed when gCYTb5-IV containing a mutated
      heme-binding site was expressed. The electrons for Giardia cytb5 proteins may be
      provided by the NADPH-dependent Tah18-like oxidoreductase GiOR-1. Therefore, GiOR
      1 and cytb5 may constitute a novel redox system in G. intestinalis. To our
      knowledge, G. intestinalis is the first anaerobic eukaryote in which the presence
      of heme has been directly demonstrated. 

PMID- 24297441
TI  - Protein kinase A is part of a mechanism that regulates nuclear reimport of the
      nuclear tRNA export receptors Los1p and Msn5p.
AB  - The two main signal transduction mechanisms that allow eukaryotes to sense and
      respond to changes in glucose availability in the environment are the cyclic AMP
      (cAMP)/protein kinase A (PKA) and AMP-activated protein kinase (AMPK)/Snf1 kinase
      dependent pathways. Previous studies have shown that the nuclear tRNA export
      process is inhibited in Saccharomyces cerevisiae deprived of glucose. However,
      the signal transduction pathway involved and the mechanism by which glucose
      availability regulates nuclear-cytoplasmic tRNA trafficking are not understood.
      Here, we show that inhibition of nuclear tRNA export is caused by a block in
      nuclear reimport of the tRNA export receptors during glucose deprivation.
      Cytoplasmic accumulation of the tRNA export receptors during glucose deprivation
      is not caused by activation of Snf1p. Evidence obtained suggests that PKA is part
      of the mechanism that regulates nuclear reimport of the tRNA export receptors in
      response to glucose availability. This mechanism does not appear to involve
      phosphorylation of the nuclear tRNA export receptors by PKA. The block in nuclear
      reimport of the tRNA export receptors appears to be caused by activation of an
      unidentified mechanism when PKA is turned off during glucose deprivation. Taken
      together, the data suggest that PKA facilitates return of the tRNA export
      receptors to the nucleus by inhibiting an unidentified activity that facilitates
      cytoplasmic accumulation of the tRNA export receptors when glucose in the
      environment is limiting. A PKA-independent mechanism was also found to regulate
      nuclear tRNA export in response to glucose availability. This mechanism, however,
      does not regulate nuclear reimport of the tRNA export receptors. 

PMID- 24297442
TI  - The 3' overhangs at Tetrahymena thermophila telomeres are packaged by four
      proteins, Pot1a, Tpt1, Pat1, and Pat2.
AB  - Although studies with the ciliate Tetrahymena thermophila have played a central
      role in advancing our understanding of telomere biology and telomerase mechanisms
      and composition, the full complement of Tetrahymena telomere proteins has not yet
      been identified. Previously, we demonstrated that in Tetrahymena, the telomeric
      3' overhang is protected by a three-protein complex composed of Pot1a, Tpt1, and
      Pat1. Here we show that Tpt1 and Pat1 associate with a fourth protein, Pat2 (Pot1
      associated Tetrahymena 2). Mass spectrometry of proteins copurifying with Pat1 or
      Tpt1 identified peptides from Pat2, Pot1a, Tpt1, and Pat1. The lack of other
      proteins copurifying with Pat1 or Tpt1 implies that the overhang is protected by
      a four-protein Pot1a-Tpt1-Pat1-Pat2 complex. We verified that Pat2 localizes to
      telomeres, but we were unable to detect direct binding to telomeric DNA. Cells
      depleted of Pat2 continue to divide, but the telomeres exhibit gradual
      shortening. The lack of growth arrest indicates that, in contrast to Pot1a and
      Tpt1, Pat2 is not required for the sequestration of the telomere from the DNA
      repair machinery. Instead, Pat2 is needed to regulate telomere length, most
      likely by acting in conjunction with Pat1 to allow telomerase access to the
      telomere. 

PMID- 24297443
TI  - Mutations in Pdd1 reveal distinct requirements for its chromodomain and
      chromoshadow domain in directing histone methylation and heterochromatin
      elimination.
AB  - Pdd1, a specialized HP1-like protein, is required for genome-wide DNA
      rearrangements that restructure a previously silent germ line genome into an
      active somatic genome during macronuclear differentiation of Tetrahymena
      thermophila. We deleted or otherwise mutated conserved regions of the protein to
      investigate how its different domains promote the excision of thousands of
      internal eliminated sequences (IESs). Previous studies revealed that Pdd1
      contributes to recognition of IES loci after they are targeted by small-RNA
      guided methylation of histone H3 on lysine 27 (H3K27), subsequently aids the
      establishment of H3K9 methylation, and recruits proteins that lead to excision.
      The phenotypes we observed for different Pdd1 alleles showed that each of the two
      chromodomains and the chromoshadow domain (CSD) have distinct contributions
      during somatic genome differentiation. Chromodomain 1 (CD1) is essential for
      conjugation as either its deletion or the substitution of two key aromatic amino
      acid residues (the W97A W100A mutant) is lethal. These mutations caused
      mislocalization of a cyan fluorescent protein (CFP)-tagged protein, prevented the
      establishment of histone H3 dimethylated on K9 (H3K9me2), and abolished IES
      excision. Nevertheless, the requirement for CD1 could be bypassed by recruiting
      Pdd1 directly to an IES by addition of a specific DNA binding domain.
      Chromodomain 2 (CD2) was necessary for producing viable progeny, but low levels
      of H3K9me2 and IES excision still occurred. A mutation in the chromoshadow domain
      (CSD) prevented Pdd1 focus formation but still permitted ~17% of conjugants to
      produce viable progeny. However, this mutant was unable to stimulate excision
      when recruited to an ectopic IES, indicating that this domain is important for
      recruitment of excision factors. 

PMID- 24297444
TI  - Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite
      development in the midgut of Anopheles mosquitoes.
AB  - The prodigious rate at which malaria parasites proliferate during asexual blood
      stage replication, midgut sporozoite production, and intrahepatic development
      creates a substantial requirement for essential nutrients, including fatty acids
      that likely are necessary for parasite membrane formation. Plasmodium parasites
      obtain fatty acids either by scavenging from the vertebrate host and mosquito
      vector or by producing fatty acids de novo via the type two fatty acid
      biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium
      falciparum, the species responsible for the most lethal form of human malaria.
      Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito
      midgut oocysts and sporozoites as well as liver-stage parasites but not during
      the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl
      carrier protein, indicating that FabI functions in the apicoplast. We further
      analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional
      consequences of deleting fabI and fabB/F. Targeted deletion or disruption of
      these genes in P. falciparum did not affect asexual blood-stage replication or
      the generation of midgut oocysts; however, subsequent sporozoite development was
      abolished. We conclude that the P. falciparum FAS-II pathway is essential for
      sporozoite development within the midgut oocyst. These findings reveal an
      important distinction from the rodent Plasmodium parasites P. berghei and P.
      yoelii, where the FAS-II pathway is known to be required for normal parasite
      progression through the liver stage but is not required for oocyst development in
      the Anopheles mosquito midgut. 

PMID- 24297446
TI  - Characterization of biofilm formation and the role of BCR1 in clinical isolates
      of Candida parapsilosis.
AB  - In Candida parapsilosis, biofilm formation is considered to be a major virulence
      factor. Previously, we determined the ability of 33 clinical isolates causing
      bloodstream infection to form biofilms and identified three distinct groups of
      biofilm-forming strains (negative, low, and high). Here, we establish two
      different biofilm structures among strains forming large amounts of biofilm in
      which strains with complex spider-like structures formed robust biofilms on
      different surface materials with increased resistance to fluconazole.
      Surprisingly, the transcription factor Bcr1, required for biofilm formation in
      Candida albicans and C. parapsilosis, has an essential role only in strains with
      low capacity for biofilm formation. Although BCR1 leads to the formation of more
      and longer pseudohyphae, it was not required for initial adhesion and formation
      of mature biofilms in strains with a high level of biofilm formation.
      Furthermore, an additional phenotype affected by BCR1 was the switch in colony
      morphology from rough to crepe, but only in strains forming high levels of
      biofilm. All bcr1Delta/Delta mutants showed increased proteolytic activity and
      increased susceptibility to the antimicrobial peptides protamine and RP-1
      compared to corresponding wild-type and complemented strains. Taken together, our
      results demonstrate that biofilm formation in clinical isolates of C.
      parapsilosis is both dependent and independent of BCR1, but even in strains which
      showed a BCR1-independent biofilm phenotype, BCR1 has alternative physiological
      functions. 

PMID- 24297447
TI  - Mesenchymal phenotype after chemotherapy is associated with chemoresistance and
      poor clinical outcome in esophageal cancer.
AB  - The relationship between the epithelial-mesenchymal transition (EMT) and
      resistance to anticancer treatment has attracted attention in recent years.
      However, to date, there is no direct clinical evidence for a link between the
      mesenchymal phenotype and chemoresistance in human malignancies. The expression
      of EMT-related markers, including E-cadherin, Snail, vimentin, ZEB1, beta-catenin
      and N-cadherin was examined immunohistochemically in 185 tissue samples from
      patients with esophageal cancer (including 93 patients who received preoperative
      chemotherapy followed by surgery and 92 patients who underwent surgery without
      preoperative therapy). The relationship between the expression of the above
      markers and clinical outcome including prognosis and response to chemotherapy was
      also examined. The expression of E-cadherin, a marker of epithelial cells, was
      significantly lower in residual tumors than chemo-naive tumors (P=0.003). The
      expression of Snail (P=0.028), ZEB1 (P<0.001) and N-cadherin (P=0.001), markers
      of mesenchymal cells, was higher in residual tumors than in chemonaive tumors.
      The expression of E-cadherin correlated inversely with that of Snail (P<0.001).
      Reduced expression of E-cadherin and increased expression of Snail in residual
      tumors from patients who received chemotherapy correlated significantly with poor
      response to chemotherapy and short survival time. Multivariate analysis
      identified Snail expression as an independent prognostic factor, along with tumor
      depth, in patients who received preoperative chemotherapy for esophageal cancer.
      The results suggest transition of residual esophageal cancer cells to mesenchymal
      phenotype after chemotherapy and this contributes to resistance to chemotherapy
      and poor prognosis in patients with esophageal cancer.

PMID- 24297445
TI  - Endosymbiotic gene transfer in tertiary plastid-containing dinoflagellates.
AB  - Plastid establishment involves the transfer of endosymbiotic genes to the host
      nucleus, a process known as endosymbiotic gene transfer (EGT). Large amounts of
      EGT have been shown in several photosynthetic lineages but also in present-day
      plastid-lacking organisms, supporting the notion that endosymbiotic genes leave a
      substantial genetic footprint in the host nucleus. Yet the extent of this genetic
      relocation remains debated, largely because the long period that has passed since
      most plastids originated has erased many of the clues to how this process
      unfolded. Among the dinoflagellates, however, the ancestral peridinin-containing
      plastid has been replaced by tertiary plastids on several more recent occasions,
      giving us a less ancient window to examine plastid origins. In this study, we
      evaluated the endosymbiotic contribution to the host genome in two dinoflagellate
      lineages with tertiary plastids. We generated the first nuclear transcriptome
      data sets for the "dinotoms," which harbor diatom-derived plastids, and analyzed
      these data in combination with the available transcriptomes for kareniaceans,
      which harbor haptophyte-derived plastids. We found low level of detectable EGT in
      both dinoflagellate lineages, with only 9 genes and 90 genes of possible tertiary
      endosymbiotic origin in dinotoms and kareniaceans, respectively, suggesting that
      tertiary endosymbioses did not heavily impact the host dinoflagellate genomes. 

PMID- 24297448
TI  - Probing the stiffness of isolated nucleoli by atomic force microscopy.
AB  - In eukaryotic cells, ribosome biogenesis occurs in the nucleolus, a membraneless
      nuclear compartment. Noticeably, the nucleolus is also involved in several
      nuclear functions, such as cell cycle regulation, non-ribosomal ribonucleoprotein
      complex assembly, aggresome formation and some virus assembly. The most
      intriguing question about the nucleolus is how such dynamics processes can occur
      in such a compact compartment. We hypothesized that its structure may be rather
      flexible. To investigate this, we used atomic force microscopy (AFM) on isolated
      nucleoli. Surface topography imaging revealed the beaded structure of the
      nucleolar surface. With the AFM's ability to measure forces, we were able to
      determine the stiffness of isolated nucleoli. We could establish that the
      nucleolar stiffness varies upon drastic morphological changes induced by
      transcription and proteasome inhibition. Furthermore, upon ribosomal proteins and
      LaminB1 knockdowns, the nucleolar stiffness was increased. This led us to propose
      a model where the nucleolus has steady-state stiffness dependent on ribosome
      biogenesis activity and requires LaminB1 for its flexibility. 

PMID- 24297449
TI  - Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460
      human large-cell lung carcinoma cells in vitro and in vivo.
AB  - Suberoylanilide hydroxamic acid (SAHA), a potent pan-histone deacetylase (HDAC)
      inhibitor, has been clinically approved for the treatment of cutaneous T-cell
      lymphoma (CTCL). SAHA has also been shown to exert a variety of anticancer
      activities in many other types of tumors, however, few studies have been reported
      in large-cell lung carcinoma (LCC). Our study aimed to investigate the potential
      antitumor effects of SAHA on LCC cells. Here, we report that SAHA was able to
      inhibit the proliferation of the LCC cell line NCI-H460 in a dose- and time
      dependent manner, induced cell apoptosis and G2/M cell cycle arrest, decreased
      AKT and ERK phosphorylation, inhibited the expression of pro-angiogenic factors
      (VEGF, HIF-1alpha) in vitro, and suppressed tumor progression in an NCI-H460 cell
      nude mouse xenograft model in vivo. These results indicate that SAHA can exert
      its strong antitumor effects in LCC patient. 

PMID- 24297452
TI  - [Dental health of first molars among Westphalian immigrants and German students].
AB  - The aim of this study was to assess the health status of the occlusal surface on
      the first molars of Westphalian students, of whom 41.0% were immigrants. The
      prevalence and retention of fissure sealants (FS) and caries experience was
      scored for 161 students aged 8 and 10 years. Logistic regression analysis was
      used to predict the influence of sex, ethnicity, and retention of FS on the
      occlusal caries risk of the first molars. There was no difference in caries
      prevalence and experience in 8-year-old German students and immigrants
      (5.6%/10.5%; 0.07 DMFT/0.21 DMFT), both parameters were significantly higher in
      10-year-old immigrants than in German students (25.5%/9.5%; 0.55 DMFT/0.11 DMFT).
      The prevalence and number of molars with FS was not different between German
      students and immigrants at 8 years (39.1%, 1.28 FS; 33.8%, 0.94 FS) and at 10
      years of age (47.4%, 1.68 FS; 39.4%, 1.17 FS). The occlusal caries risk of first
      molars without FS was significantly higher in 8-year-old immigrants than in
      German students (OR 4.62). FS should be used more frequently in daily dental
      practice. To improve the quality of FS, stricter implementation of guideline
      based standards is required.

PMID- 24297450
TI  - Relative increase in lymphocytes from as early as 1 month predicts improved
      response to dasatinib in chronic-phase chronic myelogenous leukemia.
AB  - Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may
      be associated with favorable response. However, it occurs at varying times and in
      a limited subset of patients. To identify early clinical markers for favorable
      responses applicable to all patients with or without lymphocytosis, we
      prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated
      with dasatinib after intolerance/resistance to imatinib. Although absolute
      lymphocyte counts did not differ significantly until 3 months between patients
      with complete molecular response (CMR) at 12 months and those without it,
      relative increases in lymphocyte compared with baselines differed significantly
      from 1 month. Patients with relative lymphocyte counts >150 % at 1 month or >200
      % at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3 %, P =
      0.015, and 76.5 vs. 16.1 %, P < 0.0001, respectively). A relative increase in
      lymphocyte subset of CD57(+)CD14(-), CD8(+)T, or NK cells >200 % at 1 month was
      also significantly associated with a higher CMR rate. There were significant
      negative correlations between relative lymphocyte increases and BCR/ABL
      transcript levels. CD57(+)CD14(-) cells were a highly specific focus of
      proliferation. Relative increases in lymphocyte count and its subsets from 1
      month are reliable early markers of favorable responses to dasatinib.

PMID- 24297453
TI  - [Transposition of the stoma in ileal conduits: the "trouble shooting" technique
      for stomal complications].
AB  - OBJECTIVE: To investigate stoma-related complications in ileal conduits we
      present a series of 4 patients in whom we performed a transposition of the
      conduit to the contralateral side as a surgical solution for large parastomal
      hernias. PATIENTS AND METHODS: 4 patients presented between 1998 and 2009 with
      large parastomal hernias, all in the right hemi-abdomen. A transposition to the
      contralateral side was carried out. RESULTS: The postoperative course was
      uneventful in all patients. After a median follow-up of 30 months all patients
      were free of complaints regarding the new stoma site. No patient presented with
      peristomal ulcerations or a recurrent hernia during the entire time of follow-up.
      CONCLUSION: The transposition of an existing conduit and the creation of a new
      contralateral ostomy site is an effective solution for patients suffering from
      severe local ostomy complications that are not manageable otherwise.

PMID- 24297451
TI  - Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer
      reveals a critical role of transmembrane helix H1 for HDL association.
AB  - Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian
      enzyme exhibiting antiatherosclerotic activity. Despite years of research, an
      accurate model for the binding interaction between PON1 and HDL has not been
      established. However, it is reported that anchoring of PON1 to HDL is mainly
      governed by an N-terminal alpha helix H1 and another short helix H2. Here, we
      studied the molecular association of full-length human PON1 (huPON1) with a HDL
      mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and
      molecular dynamics simulations. Our results indicate that H1 is the highly
      dynamic part of huPON1, showing clockwise rotation of up to 30 degrees  within
      the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical
      distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling
      interactions of K3, R18, and R27 together with aromatic locks formed by Y187,
      Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's
      surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area
      (MM/PBSA) binding free energy calculation revealed that H1 displays greater
      binding affinity towards lipid molecules compared with H2 and H3, suggesting that
      H1 is the most probable HDL-binding domain of PON1. Binding free energy
      decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC
      membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202
      interact with DPPC lipids mainly through van der Waals interaction. Taken
      together, these results show that the transmembrane helix H1 along with the
      interfacial positively charged and aromatic resides were crucial for PON1's
      association with HDL particle. The current study will be useful towards
      understanding the antiatherosclerotic and bioscavenging properties of this
      promiscuous enzyme. 

PMID- 24297454
TI  - Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian
      replica exchange molecular dynamics.
AB  - We present a method to identify small molecule ligand binding sites and poses
      within a given protein crystal structure using GPU-accelerated Hamiltonian
      replica exchange molecular dynamics simulations. The Hamiltonians used vary from
      the physical end state of protein interacting with the ligand to an unphysical
      end state where the ligand does not interact with the protein. As replicas
      explore the space of Hamiltonians interpolating between these states, the ligand
      can rapidly escape local minima and explore potential binding sites. Geometric
      restraints keep the ligands from leaving the vicinity of the protein and an
      alchemical pathway designed to increase phase space overlap between intermediates
      ensures good mixing. Because of the rigorous statistical mechanical nature of the
      Hamiltonian exchange framework, we can also extract binding free energy estimates
      for all putative binding sites. We present results of this methodology applied to
      the T4 lysozyme L99A model system for three known ligands and one non-binder as a
      control, using an implicit solvent. We find that our methodology identifies known
      crystallographic binding sites consistently and accurately for the small number
      of ligands considered here and gives free energies consistent with experiment. We
      are also able to analyze the contribution of individual binding sites to the
      overall binding affinity. Our methodology points to near term potential
      applications in early-stage structure-guided drug discovery.

PMID- 24297456
TI  - Hypermasculinity and Sexual Risk Among Black and White Men Who Have Sex With Men
      and Women.
AB  - Men who have sex with men and women (MSMW), particularly Black MSMW, are at high
      risk for HIV. However, few studies have focused on factors that influence Black
      MSMW's specific HIV risk behaviors, and there are no evidence-based interventions
      specifically targeting this population. Some studies have suggested that
      masculine ideals are associated with high-risk sex practices and partners. Norms
      around masculinity in the social environments in which MSMW live may prohibit
      nonheterosexual identities and behaviors, may lead to internalized homophobia,
      and may promote high-risk strategies to seek male partners. Using data collected
      from 180 Black and 101 White MSMW recruited for a study to develop strategies for
      recruiting MSMW for research and services and to inform the content of HIV
      prevention messages, we examined the association between hypermasculinity ideals
      and sexual behaviors that may contribute to increased HIV risk among Black MSMW
      and a comparison group of White MSMW. Comparing Black and White MSMW, we explored
      how this association may differ by race. Multivariate models, controlling for
      sociodemographic and other covariates, indicate that hypermasculine ideals are
      associated with increased numbers of male and female partners among Black MSMW
      and an increased number of female partners among White MSMW. Hypermasculinity is
      important to address in programs that aim to reduce HIV risk among Black MSMW. 

PMID- 24297455
TI  - Multilevel Factors Associated With Overall Mortality for Men Diagnosed With
      Prostate Cancer in Florida.
AB  - To identify individual and contextual factors contributing to overall mortality
      among men diagnosed with prostate cancer in Florida, a random sample of patients
      (between October 1, 2001, and December 31, 2007) was taken from the Florida
      Cancer Data System. Patient's demographic and clinical information were obtained
      from the Florida Cancer Data System. Comorbidity was computed following the
      Elixhauser Index method. Census-tract-level socioeconomic status and farm house
      presence were extracted from Census 2000 and linked to patient data. The ratio of
      urologists and radiation oncologists to prostate cancer cases at the county level
      was computed. Multilevel logistic regression was conducted to identify
      significance of individuals and contextual factors in relation to overall
      mortality. A total of 18,042 patients were identified, among whom 2,363 died. No
      racial difference was found in our study. Being older at diagnosis, unmarried,
      current smoker, uninsured, diagnosed at late stage, with undifferentiated, poorly
      differentiated, or unknown tumor grade were significantly associated with higher
      odds of overall mortality. Living in a low-income area was significantly
      associated with higher odds of mortality (p = .0404). After adjusting for age,
      stage, and tumor grade, patients who received hormonal, combination of radiation
      with hormone therapy, and no definitive treatment had higher odds of mortality
      compared with those who underwent surgery only. A large number of comorbidities
      were associated with higher odds of mortality. Although disease-specific
      mortality was not examined, our findings suggest the importance of careful
      considerations of patient sociodemographic characteristics and their coexisting
      conditions in treatment decision making, which in turn affects mortality. 

PMID- 24297457
TI  - Lamotrigine for chronic neuropathic pain and fibromyalgia in adults.
AB  - BACKGROUND: This is an update of the original Cochrane review entitled
      Lamotrigine for acute and chronic pain published in Issue 2, 2007, and updated in
      Issue 2, 2011. Some antiepileptic medicines have a place in the treatment of
      neuropathic pain (pain due to nerve damage). This updated review adds no new
      additional studies looking at evidence for lamotrigine as an effective treatment
      for chronic neuropathic pain or fibromyalgia. The update uses higher standards of
      evidence than previously. OBJECTIVES: To assess the analgesic efficacy of
      lamotrigine in the treatment of chronic neuropathic pain and fibromyalgia, and to
      evaluate adverse effects reported in the studies. SEARCH METHODS: We identified
      randomised controlled trials (RCTs) of lamotrigine for chronic neuropathic pain
      and fibromyalgia (including cancer pain) from MEDLINE, EMBASE and the Cochrane
      Central Register of Controlled Trials (CENTRAL). We ran searches for the original
      review in 2006, in 2011 for the first update, and subsequent searches in August
      2013 for this update. We sought additional studies from the reference lists of
      the retrieved papers. The original review and first update included acute pain,
      but no acute pain studies were identified. SELECTION CRITERIA: RCTs investigating
      the use of lamotrigine (any dose, by any route, and for any study duration) for
      the treatment of chronic neuropathic pain or fibromyalgia. Assessment of pain
      intensity or pain relief, or both, using validated scales. Participants were
      adults aged 18 and over. We included only full journal publication articles. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy and
      adverse event data, and examined issues of study quality. We performed analysis
      using three tiers of evidence. The first tier used data where studies reported
      the outcome of at least 50% pain reduction from baseline, lasted at least eight
      weeks, had a parallel group design, included 200 or more participants in the
      comparison, and reported an intention-to-treat analysis. First-tier studies did
      not use last observation carried forward (LOCF) or other imputational methods for
      dropouts. The second tier used data that failed to meet this standard and second
      tier results were therefore subject to potential bias. MAIN RESULTS: Twelve
      included studies in 11 publications (1511 participants), all with chronic
      neuropathic pain: central post-stroke pain (1), chemotherapy-induced neuropathic
      pain (1), diabetic neuropathy (4), HIV-related neuropathy (2), mixed neuropathic
      pain (2), spinal cord injury-related pain (1), and trigeminal neuralgia (1). We
      did not identify any additional studies. Participants were aged between 26 and 77
      years. Study duration was two weeks in one study and at least six weeks in the
      remainder; eight were of eight-week duration or longer.No study provided first
      tier evidence for an efficacy outcome. There was no convincing evidence that
      lamotrigine is effective in treating neuropathic pain and fibromyalgia at doses
      of 200 mg to 400 mg daily. Almost 10% of participants taking lamotrigine reported
      a skin rash. AUTHORS' CONCLUSIONS: Large, high-quality, long-duration studies
      reporting clinically useful levels of pain relief for individual participants
      provided no convincing evidence that lamotrigine is effective in treating
      neuropathic pain and fibromyalgia at doses of about 200 to 400 mg daily. Given
      the availability of more effective treatments including antiepileptics and
      antidepressant medicines, lamotrigine does not have a significant place in
      therapy based on the available evidence. The adverse effect profile of
      lamotrigine is also of concern.

PMID- 24297459
TI  - The application of high-density genetic maps of rye for the detection of QTLs
      controlling morphological traits.
AB  - The development of genetic maps is, nowadays, one of the most intensive research
      activities of plant geneticists. One of the major goals of genome mapping is the
      localisation of quantitative trait loci (QTLs). This study was aimed at the
      identification of QTLs controlling morphological traits of rye and comparison of
      their localisation on genetic maps constructed with the use of genetically
      different germplasms. For QTL analyses, two high-density consensus maps of two
      populations (RIL-S and RIL-M) of recombinant inbred lines (RIL) were applied.
      Plant height (Ph), length of spikes (Sl) and the number of spikelets per spike
      (Sps) were studied in both populations. Additionally, the number of kernels per
      spike under isolation (Kps), the weight of kernels per spike (Kw) and thousand
      kernel weight (Tkw) were assessed in the RIL-M population. Except for Tkw, the
      majority of the traits were correlated to each other. The non-parametric Kruskal
      Wallis (K-W) test and composite interval mapping (CIM) revealed 18/48 and 24/18
      regions of rye chromosomes engaged in the determination of Ph, Sl and Sps in the
      RIL-S and RIL-M populations, respectively. An additional 18/15 QTLs controlling
      Kps, Kw and Tkw were detected on a map of the RIL-M population. A numerous group
      of QTLs detected via CIM remained in agreement with the genomic regions found
      when the K-W test was applied. Frequently, the intervals indicated by CIM were
      narrower. 

PMID- 24297458
TI  - Application of array comparative genomic hybridization in 256 patients with
      developmental delay or intellectual disability.
AB  - We used whole-genome exon-targeted oligonucleotide array comparative genomic
      hybridization (array CGH) in a cohort of 256 patients with developmental delay
      (DD)/intellectual disability (ID) with or without dysmorphic features, additional
      neurodevelopmental abnormalities, and/or congenital malformations. In 69
      patients, we identified 84 non-polymorphic copy-number variants, among which 41
      are known to be clinically relevant, including two recently described deletions,
      4q21.21q21.22 and 17q24.2. Chromosomal microarray analysis revealed also 15
      potentially pathogenic changes, including three rare deletions, 5q35.3, 10q21.3,
      and 13q12.11. Additionally, we found 28 copy-number variants of unknown clinical
      significance. Our results further support the notion that copy-number variants
      significantly contribute to the genetic etiology of DD/ID and emphasize the
      efficacy of the detection of novel candidate genes for neurodevelopmental
      disorders by whole-genome array CGH. 

PMID- 24297460
TI  - Bioinformatic analysis of the membrane cofactor protein CD46 and microRNA
      expression in hepatocellular carcinoma.
AB  - The therapeutic potential of membrane complement regulatory protein (mCRP)
      neutralizing antibodies is unsatisfactory, which perhaps lies in the complex role
      of mCRPs in tumor occurrence and development. As a member of the mCRPs, CD46 is a
      transmembrane protein with a cytoplasmic domain and is implicated more in the
      control of the alternative complement pathway than of the classical complement
      pathway. Growing evidence has revealed that both the CD46 signaling pathway and
      microRNAs (miRNAs) play an important role in the development and progression of
      hepatocellular carcinoma (HCC). In the present study, we analyzed mCRP expression
      in different tumor tissues by employing western blotting and qPCR. To address the
      potential role of miRNAs in CD46 signaling, we set out to profile miRNA
      expression in CD46-overexpressed and -silenced HepG2 cell lines. Furthermore,
      bioinformatic analysis was performed to identify downstream targets of CD46
      signaling. We found that the levels of CD46 expression in HCC tissues were
      significantly higher compared to that in the adjacent normal tissues. After
      complement-related gene expression profiling and unsupervised hierarchical
      clustering analysis of 10 HCC tissues, a total of 37 miRNAs showed significantly
      different expression levels before and after CD46 expression change. By
      bioinformatic analysis, we identified let-7b and miR-17 as downstream targets of
      CD46 signaling, and that the expression levels of let-7b and miR-17 were
      negatively correlated with that of CD46 in HepG2 cells. The present study
      suggests that CD46 plays an important role in HCC carcinogenesis by regulating
      let-7b and miR-17.

PMID- 24297461
TI  - Soil mobility of surface applied polyaromatic hydrocarbons in response to
      simulated rainfall.
AB  - Polyaromatic hydrocarbons (PAHs) are emitted from a variety of sources and can
      accumulate on and within surface soil layers. To investigate the level of
      potential risk posed by surface contaminated soils, vertical soil column
      experiments were conducted to assess the mobility, when leached with simulated
      rainwater, of six selected PAHs (naphthalene, phenanthrene, fluoranthene, pyrene,
      benzo(e)pyrene and benzo(ghi)perylene) with contrasting hydrophobic
      characteristics and molecular weights/sizes. The only PAH found in the leachate
      within the experimental period of 26 days was naphthalene. The lack of migration
      of the other applied PAHs was consistent with their low mobilities within the
      soil columns which generally paralleled their log K oc values. Thus, only 2.3 %
      of fluoranthene, 1.8 % of pyrene, 0.2 % of benzo(e)pyrene and 0.4 % of
      benzo(ghi)perylene were translocated below the surface layer. The PAH
      distributions in the soil columns followed decreasing power relationships with 90
      % reductions in the starting levels being shown to occur within a maximum average
      depth of 0.94 cm compared to an average starting depth of 0.5 cm. A simple
      predictive model identifies the extensive time periods, in excess of 10 years,
      required to mobilise 50 % of the benzo(e)pyrene and benzo(ghi)perylene from the
      surface soil layer. Although this reduces to between 2 and 7 years for
      fluoranthene and pyrene, it is concluded that the possibility of surface-applied
      PAHs reaching and contaminating a groundwater aquifer is unlikely.

PMID- 24297463
TI  - H-binding of size- and polarity-fractionated soil and lignite humic acids after
      removal of metal and ash components.
AB  - A fractionation technique, combining dialysis removal of metal and ash components
      with hydrofluoric acid and pH 10 citrate buffer followed by chromatography of
      dialysis permeate on XAD-8 resin at decreasing pH values, has been applied to
      lignite humic acid (lignite-HA) and soil humic acid (soil-HA). H-binding data and
      non ideal competitive adsorption-Donnan model parameters were obtained for the HA
      fractions by theoretical analysis of H-binding data which reveal a significant
      increase of the carboxyl and the phenolic charge for the lignite-HA fractions vs.
      the parental lignite humic acid (LParentalHA). The fractionated lignite-HA
      material consisted mainly of permeate fractions, some of which were fulvic acid
      like. The fractionated soil-HA material consisted mainly of large macromolecular
      structures that did not permeate the dialysis membrane during deashing.
      Chargeable groups had comparable concentrations in soil-HA fractions and parental
      soil humic acid (SParentalHA), indicating minimal interference of ash components
      with carboxyl and phenolic (and/or enolic) groups. Fractionation of HA, combined
      with theoretical analysis of H-binding, can distinguish the supramolecular vs.
      macromolecular nature of fractions within the same parental HA.

PMID- 24297462
TI  - Metal distribution and spectroscopic analysis after soil washing with chelating
      agents and humic substances.
AB  - Biodegradable chelating agents ([S,S]-ethylenediamine-N,N-disuccinic acid (EDDS)
      and glutamic-N,N-diacetic acid (GLDA)) and natural humic substances (lignite
      derived, standard, and commercially available humic acids) are potentially useful
      for enhancing soil remediation of timber treatment sites. This study integrated
      macroscopic and spectroscopic analyses to assess their influence on the
      distribution and chemical speciation of the remaining metals as well as their
      interaction with the soil surface after 48-h washing of a field-contaminated
      soil. The results demonstrated that EDDS and GLDA were an appealing alternative
      to non-biodegradable ethylenediamine-tetraacetic acid, but the three humic
      substances were less effective. As shown by sequential extractions, Cu was
      primarily extracted from the carbonate fraction while Cr and As extraction
      resulted from (co-)dissolution of the oxide fraction. As a result, the relative
      proportion of strongly bound organic matter and residual fractions increased by 7
      16 %. However, it was noteworthy that the exchangeable fraction also increased by
      5-11 %, signifying that a portion of the remaining metals was destabilized by
      chelating agents and transformed to be more labile in the treated soil. The X-ray
      photoelectron spectroscopy spectra confirmed the substantial removal of readily
      accessible Cu from the soil surface, but Cr maintained its original chemical
      forms of trivalent chromium oxides and iron-chromium coprecipitates, whereas As
      remained as arsenic trioxide/pentoxide and copper arsenate precipitates. On the
      other hand, the absence of characteristic peaks of adsorbed carboxylate groups in
      the Fourier-transform infrared (FTIR) spectra inferred that the extent of
      adsorption of chelating agents and humic substances on the bulk soil was
      insufficient to be characterized by FTIR analysis. These results suggested that
      attention should be paid to the exchangeable fraction of Cu and
      oxides/coprecipitates of As prior to possible on-site reuse of the treated soil.

PMID- 24297464
TI  - Removal of aluminium from aqueous solutions using PAN-based adsorbents:
      characterisation, kinetics, equilibrium and thermodynamic studies.
AB  - Economic adsorbents in bead form were fabricated and utilised for the adsorption
      of Al(3+) from aqueous solutions. Polyacrylonitrile (PAN) beads, PAN powder and
      the thermally treated PAN beads (250  degrees C/48 h/Ar and 600  degrees C/48
      h/Ar-H2) were characterised using different techniques including Fourier
      transform infrared spectroscopy, X-ray diffraction, specific surface analysis
      (Brunauer-Emmett-Teller), thermogravimetric analysis as well as scanning electron
      microscopy. Effects of pH, contact time, kinetics and adsorption isotherms at
      different temperatures were investigated in batch mode experiments. Aluminium
      kinetic data best fit the Lagergren pseudo-second-order adsorption model
      indicating a one-step, surface-only, adsorption process with chemisorption being
      the rate limiting step. Equilibrium adsorption data followed a Langmuir
      adsorption model with fairly low monolayer adsorption capacities suitable for
      freshwater clean-up only. Various constants including thermodynamic constants
      were evaluated from the experimental results obtained at 20, 40 and 60  degrees
      C. Positive values of DeltaH degrees  indicated that the adsorption of Al(3+)
      onto all three adsorbents was endothermic with less energy input required for PAN
      powder compared to PAN beads and low-temperature thermally treated PAN. Negative
      DeltaG degrees  values indicated that the aluminium adsorption process was
      spontaneous for all adsorbents examined.

PMID- 24297465
TI  - Interactive effects of different inorganic As and Se species on their uptake and
      translocation by rice (Oryza sativa L.) seedlings.
AB  - There is a lack of information on the interactive relationship of absorption and
      transformation between two inorganic arsenic (As) species and two inorganic
      selenium (Se) species in rice grown under hydroponic condition. Interactive
      effects of inorganic As (As(III)) and (As(V)) and Se (Se(IV)and Se(VI)) species
      on their uptake, accumulation, and translocation in rice (Oryza sativa L.)
      seedlings were investigated in hydroponic culture. The results clearly showed the
      interactive effects of inorganic As and Se on their uptake by rice. The presence
      of Se reduced the sum of As species in the rice shoots regardless of Se
      speciation. If Se is present as Se(IV), then is it is accompanied by a
      corresponding increase of the sum of As species, but if Se is present as Se(VI),
      then there is no change in the sum of As species in rice roots. These effects are
      observed regardless of initial As speciation. When the rice plants are exposed to
      Se(IV), the presence of As increases the sum of Se species in the roots, and
      decreases the sum of Se species in the corresponding shoots. This effect is more
      pronounced for As(III) than for As(V). There is no effect on Se during exposure
      to Se(VI). Co-existence of As also increased SeMet in rice roots.

PMID- 24297466
TI  - Response of Brazilian native trees to acute ozone dose.
AB  - Ozone (O3) is a toxic secondary pollutant able to cause an intense oxidative
      stress that induces visual symptoms on sensitive plant species. Controlled
      fumigation experiment was conducted with the aim to verify the O3 sensibility of
      three tropical species: Piptadenia gonoachanta (Mart.) Macbr. (Fabaceae),
      Astronium graveolens Jacq. (Anacardiaceae), and Croton floribundus Spreng.
      (Euphorbiaceae). The microscopical features involved in the oxidative stress were
      recognized based on specific histochemical analysis. The three species showed
      visual symptoms, characterized as necrosis and stippling between the veins,
      mostly visible on the adaxial leaf surface. All the studied species presented
      hypersensitive-like response (HR-like), and peroxide hydrogen accumulation (H2O2)
      followed by cell death and proanthocyanidin oxidation in P. gonoachanta and A.
      graveolens. In P. gonoachanta, a decrease in chlorophyll autofluorescence
      occurred on symptomatic tissues, and in A. graveolens and C. floribundus, a
      polyphenol compound accumulation occurred. The responses of Brazilian native
      species were similar to those described for sensitive species from temperate
      climate, and microscopical markers may be useful for the detection of ozone
      symptoms in future studies in the field.

PMID- 24297468
TI  - Epidemiology of molluscum contagiosum in children: a systematic review.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a common skin condition that primarily
      affects children, a common reason for presenting in primary care and is commonly
      seen in children presenting with other conditions in primary and secondary care.
      It is usually asymptomatic but can present with pain, pruritus, erythema and
      bacterial superinfection. Aim. To synthesize the current epidemiology of MC.
      Design and setting. A systematic literature review of bibliographical databases
      on the prevalence, incidence, risk factors, age distribution and association with
      other conditions for MC in children. RESULTS: Data on the epidemiology of MC is
      largely of poor quality. The largest incidence is in children aged between 0 and
      14 years, where the incidence rate ranged from 12 to 14 episodes per 1000
      children per year. Incidence rates in the UK were highest in those aged 1-4
      years. Meta-analysis suggests a point prevalence in children aged 0-16 years of
      between 5.1% and 11.5%. There is evidence for an association between swimming and
      having MC and MC is more common in those with eczema; however, there is little
      evidence for other risk factors. CONCLUSIONS: MC is a common condition, with the
      greatest incidence being in those aged 1-4 years. Swimming and eczema are
      associated with the presence of MC, but the causal relationships are unclear.
      There is a lack of data regarding the natural history of MC and published data
      are insufficient to determine temporal or geographic patterns in incidence, risk
      factors, duration of symptoms or transmission between family members.

PMID- 24297467
TI  - Novel putative mechanisms to link circadian clocks to healthy aging.
AB  - The circadian clock coordinates the internal physiology to increase the
      homeostatic capacity thereby providing both a survival advantage to the system
      and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms
      are likely to play a role in regulating human health and may contribute to the
      aging process. Our aim is to give an overview of how the central clock in the
      hypothalamus and peripheral clocks relate to aging and metabolic disorders,
      including hyperlipidemia and hyperglycemia. In particular, we unravel novel
      putative mechanisms to link circadian clocks to healthy aging. This review may
      lead to the design of large-scale interventions to help people stay healthy as
      they age by adjusting daily activities, such as feeding behavior, and or
      adaptation to age-related changes in individual circadian rhythms. 

PMID- 24297469
TI  - Shift work and risk of non-cancer mortality in a cohort of German male chemical
      workers.
AB  - OBJECTIVES: Shift work is widely considered to be a health risk. In a previous
      study, we observed no elevated risk of total mortality in BASF shift workers
      followed up until the end of 2006. The present study aims to investigate non
      cancer mortality, especially mortality caused by ischaemic heart disease (IHD),
      relative to shift work. METHODS: The cohort consisted of 14,038 male shift and
      17,105 male day workers from manufacturing plants, who were employed for at least
      1 year between 1995 and 2005. Vital status was followed from 2000 to 2009. Cause
      specific mortality was obtained from death certificates. Non-cancer mortality as
      well as mortality specific to diagnoses from I20.0 to I25.9 according to
      International Classification of Disease version 10 was compared between the two
      working-time systems. To estimate the impact of shift work on the outcome of
      interest, Cox proportional hazard model was used to adjust for potential
      confounders such as age, smoking, alcohol consumption, job level, and disease
      status at baseline. The effect estimates were then given as hazard ratio (HR)
      with 95 % confidence interval (CI). RESULTS: Between 2000 and 2009, a total of
      1,062 deaths occurred in the cohort: 513 (3.6 %) in shift and 549 (3.2 %) in day
      workers. Among them were 122 deaths resulting from IHD, 55 (0.39 %) and 67 (0.39
      %), respectively. After adjustment for age at entry and job level, no increased
      risk of non-cancer mortality (HR 0.94; 95 % CI 0.77-1.15) as well as of IHD
      caused mortality was found among shift workers (HR 0.77; 95 % CI 0.52-1.14). The
      risk estimates were robust after further adjustment for more factors in all
      models and consistently tended to be in favour of shift workers. Considering the
      duration of exposure to shift, no dose-response relationship was found.
      CONCLUSION: The present analysis does not find strong evidence for an increased
      mortality risk due to non-cancer disease and, more specifically, IHD-caused
      mortality associated with this shift system. Initial selection based on health
      criteria as well as ongoing health surveillance and health promotion is likely to
      have contributed to this result. Shift work over 34 years may lead to a loss of
      this initial selection advantage over time, but the respective risk estimates
      lacked statistical precision.

PMID- 24297470
TI  - Linkage determination of linear oligosaccharides by MS(n) (n > 2) collision
      induced dissociation of Z1 ions in the negative ion mode.
AB  - Obtaining unambiguous linkage information between sugars in oligosaccharides is
      an important step in their detailed structural analysis. An approach is described
      that provides greater confidence in linkage determination for linear
      oligosaccharides based on multiple-stage tandem mass spectrometry (MS(n), n >2)
      and collision-induced dissociation (CID) of Z1 ions in the negative ion mode.
      Under low energy CID conditions, disaccharides (18)O-labeled on the reducing
      carbonyl group gave rise to Z1 product ions (m/z 163) derived from the reducing
      sugar, which could be mass-discriminated from other possible structural isomers
      having m/z 161. MS(3) CID of these m/z 163 ions showed distinct fragmentation
      fingerprints corresponding to the linkage types and largely unaffected by sugar
      unit identities or their anomeric configurations. This unique property allowed
      standard CID spectra of Z1 ions to be generated from a small set of disaccharide
      samples that were representative of many other possible isomeric structures. With
      the use of MS(n) CID (n = 3 - 5), model linear oligosaccharides were dissociated
      into overlapping disaccharide structures, which were subsequently fragmented to
      form their corresponding Z1 ions. CID data of these Z1 ions were collected and
      compared with the standard database of Z1 ion CID using spectra similarity scores
      for linkage determination. As the proof-of-principle tests demonstrated, we
      achieved correct determination of individual linkage types along with their
      locations within two trisaccharides and a pentasaccharide. 

PMID- 24297471
TI  - Unblocking the sink: improved CID-based analysis of phosphorylated peptides by
      enzymatic removal of the basic C-terminal residue.
AB  - A one-step enzymatic reaction for improving the collision-induced dissociation
      (CID)-based tandem mass spectrometry (MS/MS) analysis of phosphorylated peptides
      in an ion trap is presented. Carboxypeptidase-B (CBP-B) was used to selectively
      remove C-terminal arginine or lysine residues from phosphorylated tryptic/Lys-C
      peptides prior to their MS/MS analysis by CID with a Paul-type ion trap. Removal
      of this basic C-terminal residue served to limit the extent of gas-phase neutral
      loss of phosphoric acid (H3PO4), favoring the formation of diagnostic b and y
      ions as determined by an increase in both the number and relative intensities of
      the sequence-specific product ions. Such differential fragmentation is
      particularly valuable when the H3PO4 elimination is so predominant that
      localizing the phosphorylation site on the peptide sequence is hindered.
      Improvement in the quality of tandem mass spectral data generated by CID upon CBP
      B treatment resulted in greater confidence both in assignment of the
      phosphopeptide primary sequence and for pinpointing the site of phosphorylation.
      Higher Mascot ion scores were also generated, combined with lower expectation
      values and higher delta scores for improved confidence in site assignment; Ascore
      values also improved. These results are rationalized in accordance with the
      accepted mechanisms for the elimination of H3PO4 upon low energy CID and insights
      into the factors dictating the observed dissociation pathways are presented. We
      anticipate this approach will be of utility in the MS analysis of phosphorylated
      peptides, especially when alternative electron-driven fragmentation techniques
      are not available. 

PMID- 24297472
TI  - Structural characterization of actinomycin D using multiple ion isolation and
      electron induced dissociation.
AB  - Non-ribosomal peptides are bio synthesized using a range of enzymes that allow
      much more structural variability compared with "normal" peptides. Deviations from
      the standard amino acid structures are common features of this diverse class of
      natural products, making sequencing a challenging process. FTICR mass
      spectrometry, specifically the complementary tandem mass spectrometry techniques
      collision activated dissociation (CAD) and electron induced dissociation (EID),
      have been used to reveal structural information on the non-ribosomal peptide
      actinomycin D. EID was also combined with a multiple ion isolation method in
      order to provide an accurate (sub-ppm) internal calibration for the product ions.
      EID has been found to produce more detailed, complementary data than CAD for
      actinomycin D, with additional information being provided through fragmentation
      of the sodium and lithium adducts. Furthermore, the use of isolation in the FTICR
      cell was found to increase product ion intensities relative to the precursor ion,
      enabling significantly more peaks to be detected than when using EID alone. The
      combination of multiple ion isolation with EID, therefore, enables an accurate
      internal calibration of the fragment ions to be made (average mass uncertainty of
      <0.3 ppm), as well as increasing the degree of fragmentation of the compound,
      resulting in detailed structural information. 

PMID- 24297473
TI  - Advantages of monodisperse and chemically robust "SpheriCal" polyester dendrimers
      as a "universal" MS calibrant.
AB  - The utilization of dendrimer calibrants as an alternative to peptides and
      proteins for high mass calibration is explored. These synthetic macromolecules
      exhibited a number of attractive advantages, including exceptional shelf-lives,
      broad compatibility with a wide range of matrices and solvents, and evenly spaced
      calibration masses across the mass range examined, 700-30,000 u. The exceptional
      purity of these dendrimers and the technical simplicity of this calibration
      platform validate their broad relevance for high molecular weight mass
      spectrometry.

PMID- 24297474
TI  - Use of the "NYC Condom" among people who use drugs.
AB  - We assessed awareness and use of the "NYC Condom" among persons who use heroin
      and cocaine in New York City. The NYC Condom distribution program is the largest
      free condom distribution program in the USA, with over 30 million condoms
      distributed per year. It includes a condom social marketing program for a
      specific brand, the NYC Condom with its own packaging and advertising. People who
      use heroin and cocaine are at relatively high risk for HIV infection and are an
      important target population for the program. In order to assess awareness of the
      NYC Condom, structured interviews and blood testing for HIV, HSV-2, and sexually
      transmitted infections (STI) were conducted among entrants to the Beth Israel
      Medical Center drug detoxification and methadone treatment programs. Participants
      were asked about drug use, sexual risk behaviors, and awareness and use of the
      NYC Condom. Univariate and multivariable regression analyses were conducted to
      examine the associations between use of NYC Condoms and consistent condom use
      with primary and casual sexual partners. A total of 970 subjects were recruited
      between February 2011 and December 2012. Subjects were primarily African-American
      and Hispanic, with a mean age of 43. Fifty-five percent of subjects reported
      being sexually active with primary sexual partners, and 25 % reported being
      sexually active with a casual partner for the 6 months prior to the interview.
      Sixty-five percent of subjects had heard of the NYC Condom, 48 % of those who had
      heard of the condom had used it, and 58 % of those who had ever used it were
      currently using it (in the previous 6 months). In multivariable regression
      analyses, current use of NYC Condoms was strongly associated with consistent
      condom use with primary sexual partners (adjusted odds ratio (AOR) = 3.99, 95 %
      confidence interval (CI) 1.85-8.58) and consistent condom use with casual sexual
      partners (AOR = 4.48, 95 % CI 1.49-13.42). In terms of market share, 38 % of
      subjects consistently using condoms with primary partners were using the NYC
      Condom, and 47 % of those consistently using condoms with casual partners were
      using the NYC Condom. The NYC Condom is an important tool for reducing sexual
      transmission of HIV and STI among persons who use drugs in the city. Given the
      strong relationship between using the NYC Condom and consistent condom use,
      further efforts to promote the NYC Condom brand would be easily justified.

PMID- 24297475
TI  - A comparison of social and spatial determinants of health between formal and
      informal settlements in a large metropolitan setting in Brazil.
AB  - Urban informal settlements are often under-recognized in national and regional
      surveys. A lack of quality intra-urban data frequently contributes to a one-size
      fits-all public health intervention and clinical strategies that rarely address
      the variegated socioeconomic disparities across and within different informal
      settlements in a city. The 2010 Brazilian census gathered detailed population and
      place-based data across the country's informal settlements. Here, we examined key
      socio-demographic and infrastructure characteristics that are associated with
      health outcomes in Rio de Janeiro with the census tract as the unit of analysis.
      Many of the city's residents (1.39 million people, 22 % of the population) live
      in informal settlements. Residents of census tracts in Rio de Janeiro's urban
      informal areas are younger, (median age of 26 versus 35 years in formal
      settlements), and have less access to adequate water (96 versus 99 % of informal
      households), sanitation (86 versus 96 %), and electricity (67 versus 92 %).
      Average per household income in informal settlement census tracts is less than
      one third that of non-informal tracts (US?$708 versus US?$2362). Even among
      informal settlements in different planning areas in the same city, there is
      marked variation in these characteristics. Public health interventions, clinical
      management, and urban planning policies aiming to improve the living conditions
      of the people residing in informal settlements, including government strategies
      currently underway, must consider the differences that exist between and within
      informal settlements that shape place-based physical and social determinants of
      health.

PMID- 24297476
TI  - Extreme heat awareness and protective behaviors in New York City.
AB  - Heat waves can be lethal and routinely prompt public warnings about the dangers
      of heat. With climate change, extreme heat events will become more frequent and
      intense. However, little is known about public awareness of heat warnings or
      behaviors during hot weather. Awareness of heat warnings, prevention behaviors,
      and air conditioning (AC) prevalence and use in New York City were assessed using
      quantitative and qualitative methods. A random sample telephone survey was
      conducted in September 2011 among 719 adults and follow-up focus groups were held
      in winter 2012 among seniors and potential senior caregivers. During summer 2011,
      79 % of adults heard or saw a heat warning. Of the 24 % who were seniors or in
      fair or poor health, 34 % did not own AC or never/rarely used it on hot days. Of
      this subgroup, 30 % were unaware of warnings, and 49 % stay home during hot
      weather. Reasons for not using AC during hot weather include disliking AC (29 %),
      not feeling hot (19 %), and a preference for fans (18 %). Seniors in the focus
      groups did not perceive themselves to be at risk, and often did not identify AC
      as an important health protection strategy. While heat warnings are received by
      most New Yorkers, AC cost, risk perception problems, and a preference for staying
      home leave many at risk during heat waves. Improving AC access and risk
      communications will help better protect the most vulnerable during heat waves.

PMID- 24297477
TI  - Clinical significance of TrkB expression in nasopharyngeal carcinoma.
AB  - Recent research has demonstrated that tropomyosin-related kinase B (TrkB) plays
      an important role in neuronal survival, differentiation and migration; yet, its
      specific role in human nasopharyngeal carcinoma (NPC) is unclear. To elucidate
      its role in NPC, we examined TrkB expression in NPC tissues and cell lines, and
      investigated the correlation between TrkB expression and prognosis in patients
      with NPC. Immunohistochemical analysis was performed on NPC specimens from 108
      patients with follow-up information. Additionally, reverse transcriptase
      polymerase chain reaction (RT-PCR) and western blot analyses were used to
      determine TrkB expression levels in NPC and noncancerous nasopharyngeal tissues.
      RT-PCR and western blot analyses were also used to determine TrkB expression
      levels in 7 NPC cell lines and a nasopharyngeal epithelium cell line. High TrkB
      expression was significantly correlated with T classification, lymph node
      metastasis and clinical stage, respectively. Patients with NPC who had high TrkB
      expression had reduced disease-free survival and overall survival when compared
      with patients who had low TrkB expression. Multivariate Cox regression analysis
      revealed that TrkB overexpression was an independent prognostic factor for
      patients with NPC. Furthermore, TrkB was overexpressed in NPC specimens and cell
      lines. TrkB expression levels were significantly increased in NPC specimens, and
      enhanced levels were correlated with a poor prognosis in patients with NPC. These
      findings suggest that TrkB may contribute to NPC progression and represent a
      novel prognostic indicator for patients with NPC.

PMID- 24297478
TI  - Characterization of a novel melamine-degrading bacterium isolated from a melamine
      manufacturing factory in China.
AB  - Melamine (2,4,6-triamino-1,3,5-triazine, C3H6N6), belonging to the s-triazine
      family, is an anthropogenic and versatile raw material for a large number of
      consumer products and its extensive use has resulted in the contamination of
      melamine in the environment. A novel melamine-degrading bacterium strain CY1 was
      isolated from a melamine-manufacturing factory in China. The strain is
      phylogenetically different from the known melamine-degrading bacteria.
      Approximately, 94 % melamine (initial melamine concentration 4.0 mM, initial cell
      OD 0.05) was degraded in 10 days without the addition of additional carbon
      source. High-performance liquid chromatography showed the production of
      degradation intermediates including ammeline, ammelide, cyanuric acid, biuret,
      and urea. Kinetic simulation analysis indicated that transformation of urea into
      ammonia was the rate-limiting step for the degradation process. The melamine
      cyanurate complex was formed due to self-assembly of melamine and cyanuric acid
      during the degradation. The tracking experiment using CY1 cells and (13)C3
      melamine showed that the CY1 could mineralize s-triazine ring carbon to CO2. The
      strain CY1 could also catalyze partial transformation of cyromazine, a
      cyclopropyl derivative of melamine, to 6-(cyclopropylamino)-[1,3,5]triazine-2,4
      diol.

PMID- 24297479
TI  - Toxic effects of nanoparticles on bioluminescence activity, seed germination, and
      gene mutation.
AB  - The potential environmental toxicities of several metal oxide nanoparticles (NPs;
      CuO, TiO2, NiO, Fe2O3, ZnO, and Co3O4) were evaluated in the context of
      bioluminescence activity, seed germination, and bacterial gene mutation. The
      bioassays exhibited different sensitivities, i.e., each kind of NP exhibited a
      different level of toxicity in each of the bioassays. However, with a few
      exceptions, CuO and ZnO NPs had most toxic for germination of Lactuca seed (EC50
      0.46 mg CuO/l) and bioluminescence (EC50 1.05 mg ZnO/l). Three NPs (Co3O4, TiO2,
      and Fe2O3) among all tested concentrations (max. 1,000 mg/l) showed no inhibitory
      effects on the tested organisms, except for Co3O4 NPs on bioluminescence activity
      (EC50 62.04 mg/l). The sensitivity of Lactuca seeds was greater than that of
      Raphanus seeds (EC50 0.46 mg CuO/l versus 26.84 mg CuO /l ). The ranking of metal
      toxicity levels on bioluminescence was in the order of ZnO > CuO > Co3O4 > NiO >
      Fe2O3, TiO2, while CuO > ZnO > NiO > Co3O4, Fe2O3, TiO2 on germination. No
      revertant mutagenic ratio (greater than 2.0) of Salmonella typhimurium TA 98 was
      observed under any tested condition. These findings demonstrate that several
      bioassays, as opposed to any single one, are needed for the accurate assessment
      of NP toxicity on ecosystems.

PMID- 24297480
TI  - Genome engineering of Agrobacterium tumefaciens using the lambda Red
      recombination system.
AB  - Agrobacterium tumefaciens has been widely used as a tool for transgenesis in
      plants. The availability of its genome sequence should facilitate the directed
      engineering of improved properties; however, the current genome engineering
      options are laborious. Here, we investigated whether the lambda Red operon can be
      applied for recombineering of the A. tumefaciens genome. First, we built an
      expression plasmid for A. tumefaciens employing a tetracycline-inducible promoter
      to regulate the Red operon. This multicopy plasmid was then itself modified in A.
      tumefaciens to verify that the Red operon was functional. Then, we modified the
      endogenous A. tumefaciens tumor-inducing plasmid and the linear chromosome. These
      results extend recombineering technology to a new host and indicate a fast and
      convenient way to engineer the A. tumefaciens genome for functional genomics and
      strain improvements.

PMID- 24297481
TI  - Characterization of the small heat shock protein Hsp27 gene in Chironomus
      riparius (Diptera) and its expression profile in response to temperature changes
      and xenobiotic exposures.
AB  - Small heat shock proteins constitute the most diverse and least conserved group
      within the large family of heat shock proteins, which play a crucial role in cell
      response to environmental insults. Chironomus riparius larvae are widely used in
      environmental research for testing pollutant toxicity in sediments and freshwater
      environments. Different genes, such as Hsp70, Hsc70, Hsp90, and Hsp40, have been
      identified in this species as sensitive biomarkers for xenobiotics, but small
      Hsps genes remain largely unknown. In this study, the Hsp27 has been
      characterized in C. riparius and its transcriptional response evaluated under
      several environmental stimuli. The Hsp27 gene was mapped by FISH on polytene
      chromosomes at region I-C4 and was found to encode a 195 aa protein, which
      contains an alpha-crystallin domain bounded by three conserved regions. This
      protein shows homology with Drosophila melanogaster HSP27, Ceratitis capitata
      HSP27, and Sarcophaga crassipalpis HSP25. Real-time reverse transcriptase
      polymerase chain reaction analysis showed that heat shock (35  degrees C) and
      cadmium dramatically upregulate this gene. Moreover, exposures to triclosan and
      bisphenol A were able to significantly increase mRNA levels. However, neither
      nonylphenol nor tributyltin altered Hsp27 gene expression. The transcriptional
      activity of Hsp27 gene was modulated during cold stress. Interestingly, cold
      shock (4  degrees C) significantly reduced Hsp27 transcripts, but this gene was
      significantly overexpressed during the recovery time at the normal growing
      temperature. These results show that the Hsp27 gene is sensitive to different
      environmental stimuli, including endocrine-disrupting pollutants, suggesting its
      potential as a suitable biomarker for ecotoxicological studies in aquatic
      systems. 

PMID- 24297483
TI  - Evidence that depletion of the sorting nexin 1 by siRNA promotes HGF-induced MET
      endocytosis and MET phosphorylation in a gefitinib-resistant human lung cancer
      cell line.
AB  - The receptor tyrosine kinase MET and its ligand HGF are known to be overexpressed
      in malignant tumor cells, and they have been implicated in gefitinib resistance
      in lung cancer cells. We recently found that sorting nexin 1 (SNX1), a protein
      that interacts with EGFR, exhibited negative regulation of EGFR trafficking out
      of early to late endosomes in gefitinib-resistant NSCLC cell lines. To
      investigate the role of SNX1 on HGF-stimulated MET endocytosis and its
      downregulation via the early/late endocytic pathway, we examined the effect of
      depletion of SNX1 expression by siRNA in NSCLC cells. Using immunofluorescence,
      we found that the silencing of SNX1 by siRNA caused a dramatic change in the
      intracellular distribution of plasma membrane-associated MET and that the
      resultant MET staining was spread throughout the cytoplasm, and it co-localized
      well with the endocytosed Texas red-labeled transferrin in the siRNA-SNX1
      transfected cells. We also found efficient MET phosphorylation and rapid
      endocytic delivery of phosphorylated MET from early endosomes to late endosomes
      in the siRNA-SNX1-transfected cells. By contrast, the siRNA-control transfected
      cells showed inefficient endocytic delivery of phosphorylated MET from early
      endosomes to late endosomes. Furthermore, large amounts of phosphorylated MET
      that had accumulated in late endosomes were seen even after 60 min of HGF
      stimulation in the presence of bafilomycin A1, indicating that degradation of
      phosphorylated MET proceeds in a late endosome/lysosome pathway. Western blot
      analysis revealed that depletion of SNX1 by siRNA induced a maximal and dramatic
      increase in phosphorylated MET at 60 min, followed by an accelerated degradation
      of phosphorylated MET after HGF stimulation in the cells. Taken together, we
      suggest that SNX1 plays a suppressive role in the regulation of HGF-stimulated
      MET/phosphorylated MET endocytosis and downregulation via the early/late
      endocytic pathway in the gefitinib-resistant NSCLC cells.

PMID- 24297482
TI  - Strategies to improve retention in randomised trials.
AB  - BACKGROUND: Loss to follow-up from randomised trials can introduce bias and
      reduce study power, affecting the generalisability, validity and reliability of
      results. Many strategies are used to reduce loss to follow-up and improve
      retention but few have been formally evaluated. OBJECTIVES: To quantify the
      effect of strategies to improve retention on the proportion of participants
      retained in randomised trials and to investigate if the effect varied by trial
      strategy and trial setting. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO,
      DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and
      Criminological Trials Register, and ERIC. We handsearched conference proceedings
      and publication reference lists for eligible retention trials. We also surveyed
      all UK Clinical Trials Units to identify further studies. SELECTION CRITERIA: We
      included eligible retention trials of randomised or quasi-randomised evaluations
      of strategies to increase retention that were embedded in 'host' randomised
      trials from all disease areas and healthcare settings. We excluded studies aiming
      to increase treatment compliance. DATA COLLECTION AND ANALYSIS: We contacted
      authors to supplement or confirm data that we had extracted. For retention
      trials, we recorded data on the method of randomisation, type of strategy
      evaluated, comparator, primary outcome, planned sample size, numbers randomised
      and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of
      the addition of strategies to improve retention. We assessed heterogeneity
      between trials using the Chi(2) and I(2) statistics. For main trials that hosted
      retention trials, we extracted data on disease area, intervention, population,
      healthcare setting, sequence generation and allocation concealment. MAIN RESULTS:
      We identified 38 eligible retention trials. Included trials evaluated six broad
      types of strategies to improve retention. These were incentives, communication
      strategies, new questionnaire format, participant case management, behavioural
      and methodological interventions. For 34 of the included trials, retention was
      response to postal and electronic questionnaires with or without medical test
      kits. For four trials, retention was the number of participants remaining in the
      trial. Included trials were conducted across a spectrum of disease areas,
      countries, healthcare and community settings. Strategies that improved trial
      retention were addition of monetary incentives compared with no incentive for
      return of trial-related postal questionnaires (RR 1.18; 95% CI 1.09 to 1.28, P
      value < 0.0001), addition of an offer of monetary incentive compared with no
      offer for return of electronic questionnaires (RR 1.25; 95% CI 1.14 to 1.38, P
      value < 0.00001) and an offer of a GBP20 voucher compared with GBP10 for return
      of postal questionnaires and biomedical test kits (RR 1.12; 95% CI 1.04 to 1.22,
      P value < 0.005). The evidence that shorter questionnaires are better than longer
      questionnaires was unclear (RR 1.04; 95% CI 1.00 to 1.08, P value = 0.07) and the
      evidence for questionnaires relevant to the disease/condition was also unclear
      (RR 1.07; 95% CI 1.01 to 1.14). Although each was based on the results of a
      single trial, recorded delivery of questionnaires seemed to be more effective
      than telephone reminders (RR 2.08; 95% CI 1.11 to 3.87, P value = 0.02) and a
      'package' of postal communication strategies with reminder letters appeared to be
      better than standard procedures (RR 1.43; 95% CI 1.22 to 1.67, P value < 0.0001).
      An open trial design also appeared more effective than a blind trial design for
      return of questionnaires in one fracture prevention trial (RR 1.37; 95% CI 1.16
      to 1.63, P value = 0.0003).There was no good evidence that the addition of a non
      monetary incentive, an offer of a non-monetary incentive, 'enhanced' letters,
      letters delivered by priority post, additional reminders, or questionnaire
      question order either increased or decreased trial questionnaire
      response/retention. There was also no evidence that a telephone survey was either
      more or less effective than a monetary incentive and a questionnaire. As our
      analyses are based on single trials, the effect on questionnaire response of
      using offers of charity donations, sending reminders to trial sites and when a
      questionnaire is sent, may need further evaluation. Case management and
      behavioural strategies used for trial retention may also warrant further
      evaluation. AUTHORS' CONCLUSIONS: Most of the retention trials that we identified
      evaluated questionnaire response. There were few evaluations of ways to improve
      participants returning to trial sites for trial follow-up. Monetary incentives
      and offers of monetary incentives increased postal and electronic questionnaire
      response. Some other strategies evaluated in single trials looked promising but
      need further evaluation. Application of the findings of this review would depend
      on trial setting, population, disease area, data collection and follow-up
      procedures.

PMID- 24297484
TI  - Metabolic parameters and adipokine profile in growth hormone deficient (GHD)
      children before and after 12-month GH treatment.
AB  - It is a common knowledge that GH exhibits a large number of metabolic effects,
      involving lipid and glucose homeostasis. The aim of the study was to investigate
      the effect of one year GH therapy on metabolic parameters and adipokines in GH
      deficient (GHD) children. Sixteen prepubertal children (11 M and 5 F) with
      complete GHD (age range: 3.4-14.7 years) and 20 (13 M and 7 F) age and sex
      matched healthy children (age range: 4.6-12.3 years) were studied. Blood was
      collected from patients before starting GH therapy (0.025 mg/kg/day) and one year
      later, and from healthy children to measure adiponectin, leptin, osteoprotegerin,
      resistin, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha levels, and other
      glucose and lipid metabolism parameters. Adiponectin and resistin levels were
      significantly higher (49980 ng/ml vs. 14790 ng/ml and 11.0 pg/ml vs. 6.3,
      respectively) in GHD children before GH therapy than in controls. Serum IGF-I
      levels (p=0.0001) and height SDS (p<0.0001) significantly increased after 12
      months' of GH therapy. There was a loss of body fat reflected by a significant
      decline in tricep (p=0.0003) and subscapular skinfold thickness SDS (p=0.0023).
      After 12 months, there was a significant rise in insulin (p=0.0052) and leptin
      levels (p=0.0048) and a significant decrease in resistin (p=0.0312) and TNF-alpha
      (p=0.0137). We observed that lipid and glucose metabolisms are only slightly
      affected in GHD children. Growth hormone replacement therapy affects some
      factors, such as leptin, resistin and fat mass, suggesting that also in children,
      GH treatment has a role in the regulation of factors secreted by adipose tissue.

PMID- 24297485
TI  - Olmesartan blocks advanced glycation end products-induced vcam-1 gene expression
      in mesangial cells by restoring Angiotensin-converting enzyme 2 level.
AB  - Advanced glycation end products (AGEs) and their receptor (RAGE) system are
      involved in diabetic nephropathy. Angiotensin-converting enzyme 2 (ACE 2) plays a
      protective role against cardiovascular and renal injury by stimulating the
      production of angiotensin-(1-7) [Ang-(1-7)], an antagonist of angiotensin II (Ang
      II). However, effects of the AGEs-RAGE axis on ACE 2 expression in mesangial
      cells remain unknown. We examined here the role of ACE 2 in the AGEs-RAGE-induced
      mesangial cell damage and investigated whether olmesartan, one of the Ang II type
      1 receptor blockers (ARB), prevented the deleterious effects of AGEs via
      restoration of ACE 2 and Ang-(1-7) level. AGEs significantly increased superoxide
      generation, upregulated RAGE mRNA level, and decreased ACE 2 gene expression and
      Ang-(1-7) production in mesangial cells, all of which were blocked by olmesartan,
      but not by a different type of ARB, azilsartan. An antioxidant, N-acetylcysteine
      or RAGE-antibodies also restored the decrease in ACE 2 mRNA level in AGEs-exposed
      mesangial cells. Moreover, olmesartan, but not azilsartan completely inhibited
      the AGEs-induced increase in vascular cell adhesion molecule-1 (VCAM-1) mRNA
      level in mesangial cells, which was abolished by the treatment with A-779, an
      antagonist of Ang-(1-7) receptor, Mas receptor. Our present study suggests that
      olmesartan could block the AGEs-induced VCAM-1 gene induction in mesangial cells
      by restoring the downregulated ACE 2 levels and subsequently stimulating the Ang
      (1-7)-Mas receptor axis. Restoration of ACE 2 levels and blockade of renin
      angiotensin system by olmesartan might be a promising strategy for the treatment
      of diabetic nephropathy. 

PMID- 24297486
TI  - LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal
      adrenal cortex and aldosterone producing adenoma.
AB  - Endocrine factors different from ACTH or angiotensin II can stimulate aldosterone
      secretion and have a role in the pathophysiology of hyperaldosteronism.
      Aldosterone may increase in luteotropic/progestogenic and in hypothyroid states;
      LH and, occasionally, TSH receptors have been detected in normal adrenal cortex
      and aldosterone-producing adenoma. The aim of the study was to compare adrenal
      contents of LH and TSH receptors between normal cortex and aldosterone-producing
      adenoma and to evaluate the ability of LH, its product progesterone, and TSH to
      stimulate aldosterone secretion in vitro from primary adrenocortical cells.
      Surgical aldosterone-producing adenoma fragments from 19 patients and adrenal
      cortex fragments from 10 kidney donors were used for Western blotting and cell
      cultures. LH (n=26), TSH (n=19) and progesterone (n=8) receptor proteins were
      investigated; LH receptor-mRNA was also tested in 8 samples. Aldosterone
      responses in vitro to LH, progesterone, and TSH stimulation were assayed. LH and
      TSH receptors were more expressed in adenoma than normal cortex (p<0.01, p<0.05,
      respectively); progesterone receptor was observed in 6/8 samples. Aldosterone
      increased after in vitro stimulation with LH (5/12 adenoma, 1/7 normal cells),
      progesterone (4/5 adenoma, 5/6 normal cells), and TSH (3/5 adenoma and 3/5 normal
      cells). LH and TSH receptors were more expressed in aldosterone producing adenoma
      than normal adrenal cortex. LH, progesterone, and TSH can stimulate aldosterone
      in vitro. Similar mechanisms could participate in vivo in the aldosterone
      increase in lutheotropic, progestogenic, or hypothyroid states and may exist in
      both normal adrenal cortex and adenoma in responsive individuals. 

PMID- 24297487
TI  - TNF-alpha gene expression in subcutaneous adipose tissue associated with HOMA in
      Asian Indian postmenopausal women.
AB  - The present study determines the fat depot-specific expression of leptin and TNF
      alpha and its association with biochemical parameters in postmenopausal women. A
      total of 108 postmenopausal women were recruited prospectively; 54 were with
      metabolic syndrome (cases) and 54 were without metabolic syndrome (controls).
      Leptin and TNF-alpha mRNA expression in visceral adipose tissue (VAT) and
      subcutaneous adipose tissue (SAT) were done by Real Time-RT PCR. In cases, the
      mean (+/-SD) serum estrogen was significantly lower (41.33+/-24.90 vs. 23.95+/
      14.45, p<0.001) while leptin (12.85+/-4.51 vs. 10.34+/-3.89, p=0.002) and TNF
      alpha (13.81+/-7.13 vs. 8.00+/-4.38, p<0.001) were significantly higher as
      compared to controls. Further, the mean relative VAT mRNA expression of both
      leptin (0.33+/-0.29 vs. 0.05+/-0.09, p<0.001) and TNF-alpha (0.32+/-0.31 vs.
      0.13+/-0.09, p<0.001) and expression of SAT leptin (4.91+/-4.01 vs. 0.50+/-0.92,
      p<0.001) also lowered significantly in cases as compared to controls. Further,
      the relative VAT expression of both leptin (r=-0.32, p<0.001) and TNF-alpha (r=
      0.23, p<0.01) showed significant and negative correlation with glucose;
      expression of SAT leptin showed significant and positive correlation with HDL
      (r=0.20, p<0.05) and serum estrogen (r=0.30, p<0.01) while negative correlation
      with glucose (r=-0.26, p<0.01) and serum TNF-alpha (r=-0.29, p<0.01); and
      expression of SAT TNF-alpha showed significant and positive correlation with
      insulin (r=0.21, p<0.05) and HOMA (r=0.20, p<0.05). In conclusion, the VAT and
      SAT leptin mRNA expressions may have a modulatory role in metabolic syndrome. 

PMID- 24297488
TI  - Detection of respiratory syncytial virus fusion protein variants between 2009 and
      2012 in China.
AB  - Respiratory syncytial virus (RSV) causes respiratory tract infection,
      particularly acute lower respiratory tract infection (ALRTI), in early childhood.
      The RSV fusion protein (F protein) is an important surface protein, and it is the
      target of both cytotoxic T lymphocytes (CTL) and neutralizing antibodies; thus,
      it may be useful as a candidate for vaccine research. This study investigated the
      genetic diversity of the RSV F protein. To this end, a total of 1800
      nasopharyngeal aspirates from hospitalized children with ALRTI were collected for
      virus isolation between June 2009 and March 2012. There were 333 RSV-positive
      cases (277 cases of RSV A, 55 of RSV B, and 1 with both RSV A and RSV B),
      accounting for 18.5 % of the total cases. Next, 130 clinical strains (107 of RSV
      A, 23 of RSV B) were selected for F gene sequencing. Phylogenetic analysis
      revealed that the F gene sequence is highly conserved, with significant amino
      acid changes at residues 16, 25, 45, 102, 122, 124, 209, and 447. Mutations in
      human histocompatibility leukocyte antigen (HLA)-restricted CTL epitopes were
      also observed. Variations in RSV A F protein at the palivizumab binding site 276
      (N->S) increased between 2009 and 2012 and became predominant. Western blot
      analysis and microneutralization data showed a substitution at residue 276 (N->S)
      in RSV A that did not cause resistance to palivizumab. In conclusion, the RSV F
      gene is geographically and temporally conserved, but limited genetic variations
      were still observed. These data could be helpful for the development of vaccines
      against RSV infection.

PMID- 24297489
TI  - Isolation and characterization of a Chinese strain of Tembusu virus from Hy-Line
      Brown layers with acute egg-drop syndrome in Fujian, China.
AB  - Tembusu virus (TMUV) has been a causative agent of an acute egg-drop syndrome
      found in Chinese duck populations since at least 2010. In this paper, we report
      the characterization of a TMUV-like flavivirus (named CJD05) isolated from
      naturally infected egg-laying fowl. The virus was identified and then isolated
      from hens suffering from severe egg drop and fever in Fujian Province, China. The
      virus replicated well in MDEF and CEF cells, and its cytopathogenic effect (CPE)
      was apparent. Hemagglutinating activity (HA) was negative for this virus using
      erythrocytes from both chickens and pigeons. Viral particles were enveloped and
      approximately 45 nm in diameter, as observed by electron microscopy. Phylogenetic
      analysis of the full-length nucleotide sequence of CJD05 indicated that this
      virus is closely related to the duck-origin TMUV, belonging to Ntaya group of
      flavivirus. Most importantly, pathogenicity studies showed that CJD05 is highly
      virulent in 1-day-old chicks, 1-day-old Muscovy ducks, egg-laying chickens and
      shelducks. Our research highlights the increase in epidemic disease caused by
      avian TMUV, and subsequent outbreaks are becoming more complicated to treat. The
      pathogenic mechanisms of the virus are still not fully understood, further
      research is needed.

PMID- 24297490
TI  - Different trends of transmitted HIV-1 drug resistance in Madrid, Spain, among
      risk groups in the last decade.
AB  - The presence of transmitted HIV drug resistance (TDR) threatens the efficacy of
      antiretroviral treatment. We aimed to assess the changes in TDR prevalence over
      the last decade in Madrid, Spain, to verify the role of the patients' risk groups
      in these changes. We analysed the trends of TDR between 2000 and 2011 in a cohort
      of 1,022 naive HIV-infected patients in Madrid, Spain, whose pol sequences were
      available. They included, among others, 369 heterosexuals, 340 men who have sex
      with men (MSM), and 90 injection drug users (IDUs). TDR was reported following
      the WHO mutation list. The TDR rate in the whole cohort was 8.3 %, being the
      highest in MSM (9.1 %) and the lowest in IDUs (4.4 %). Over time, this rate
      decreased significantly (to 5.4 % in 2009-2011) since the period 2004-2006, when
      it peaked (10.7 %). Heterosexuals and IDUs showed similar trends, but in the 2009
      2011 period, the TDR rate among MSM rebounded to 9.0 % (being absent among IDUs).
      TDR stabilized in the last years (2007-2011) for nucleoside reverse transcriptase
      inhibitors. The risk group also determined differences in the mutational profile,
      sex distribution, proportion of immigrants, and viral variants. In conclusion,
      the risk group caused different HIV sub-epidemics, determined by the patients'
      profiles. Despite the general decreasing trend in TDR, we observed a non
      significant increase in TDR rate among MSM, a tendency that needs confirmation.
      Periodic TDR surveillance is important to prevent the widespread distribution of
      resistance, especially in MSM, given the growing HIV/AIDS epidemic in this high
      risk population.

PMID- 24297491
TI  - Hemagglutinin variants of influenza A(H1N1)pdm09 virus with reduced affinity for
      sialic acid receptors.
AB  - In influenza A H1 virus, amino acids at position 190 and 225 of HA affect
      replication and transmission. In this study, we show that the mutation D190Y in
      the HA of influenza AH1N1pdm09 virus reduces the affinity of the virus for sialic
      acid receptors expressed at the surface of red blood cells from different species
      without affecting virus replication in MDCK cells. 

PMID- 24297492
TI  - A perspective on immunomodulation and tissue repair.
AB  - An immune response involves the action of all types of macrophages, classically
      activated subtype (M1) in the early inflammatory phase and regulatory and wound
      healing subtypes (M2) in the resolution phase. The remarkable plasticity of
      macrophages makes them an interesting target in the context of immunomodulation.
      Here, we reviewed the current state of understanding regarding the role that
      different phenotypes of macrophages and monocytes play following injury and
      during the course of remodeling in different tissue types. Moreover, we explored
      recent designs of macrophage modulatory biomaterials for tissue engineering and
      regenerative medicine applications. 

PMID- 24297493
TI  - Multi-scale parameterisation of a myocardial perfusion model using whole-organ
      arterial networks.
AB  - A method to extract myocardial coronary permeabilities appropriate to
      parameterise a continuum porous perfusion model using the underlying anatomical
      vascular network is developed. Canine and porcine whole-heart discrete arterial
      models were extracted from high-resolution cryomicrotome vessel image stacks.
      Five parameterisation methods were considered that are primarily distinguished by
      the level of anatomical data used in the definition of the permeability and
      pressure-coupling fields. Continuum multi-compartment porous perfusion model
      pressure results derived using these parameterisation methods were compared
      quantitatively via a root-mean-square metric to the Poiseuille pressure solved on
      the discrete arterial vasculature. The use of anatomical detail to parameterise
      the porous medium significantly improved the continuum pressure results. The
      majority of this improvement was attributed to the use of anatomically-derived
      pressure-coupling fields. It was found that the best results were most reliably
      obtained by using porosity-scaled isotropic permeabilities and anatomically
      derived pressure-coupling fields. This paper presents the first continuum
      perfusion model where all parameters were derived from the underlying anatomical
      vascular network. 

PMID- 24297494
TI  - Nanomedicine: tiny particles and machines give huge gains.
AB  - Nanomedicine is an emerging field that integrates nanotechnology, biomolecular
      engineering, life sciences and medicine; it is expected to produce major
      breakthroughs in medical diagnostics and therapeutics. Nano-scale structures and
      devices are compatible in size with proteins and nucleic acids in living cells.
      Therefore, the design, characterization and application of nano-scale probes,
      carriers and machines may provide unprecedented opportunities for achieving a
      better control of biological processes, and drastic improvements in disease
      detection, therapy, and prevention. Recent advances in nanomedicine include the
      development of nanoparticle (NP)-based probes for molecular imaging, nano
      carriers for drug/gene delivery, multifunctional NPs for theranostics, and
      molecular machines for biological and medical studies. This article provides an
      overview of the nanomedicine field, with an emphasis on NPs for imaging and
      therapy, as well as engineered nucleases for genome editing. The challenges in
      translating nanomedicine approaches to clinical applications are discussed. 

PMID- 24297495
TI  - Engineering three-dimensional stem cell morphogenesis for the development of
      tissue models and scalable regenerative therapeutics.
AB  - The physiochemical stem cell microenvironment regulates the delicate balance
      between self-renewal and differentiation. The three-dimensional assembly of stem
      cells facilitates cellular interactions that promote morphogenesis, analogous to
      the multicellular, heterotypic tissue organization that accompanies
      embryogenesis. Therefore, expansion and differentiation of stem cells as
      multicellular aggregates provides a controlled platform for studying the
      biological and engineering principles underlying spatiotemporal morphogenesis and
      tissue patterning. Moreover, three-dimensional stem cell cultures are amenable to
      translational screening applications and therapies, which underscores the broad
      utility of scalable suspension cultures across laboratory and clinical scales. In
      this review, we discuss stem cell morphogenesis in the context of fundamental
      biophysical principles, including the three-dimensional modulation of adhesions,
      mechanics, and molecular transport and highlight the opportunities to employ stem
      cell spheroids for tissue modeling, bioprocessing, and regenerative therapies. 

PMID- 24297496
TI  - Nafcillin enhances innate immune-mediated killing of methicillin-resistant
      Staphylococcus aureus.
AB  - Based on in vitro synergy studies, the addition of nafcillin to daptomycin was
      used to treat refractory methicillin-resistant Staphylococcus aureus (MRSA)
      bacteremia. Daptomycin is a de facto cationic antimicrobial peptide in vivo, with
      antistaphylococcal mechanisms reminiscent of innate host defense peptides (HDPs).
      In this study, the effects of nafcillin on HDP activity against MRSA were
      examined in vitro and in vivo. Exposures to beta-lactam antimicrobials in
      general, and nafcillin in particular, significantly increased killing of S.
      aureus by selected HDPs from keratinocytes, neutrophils, and platelets. This
      finding correlated with enhanced killing of MRSA by whole blood, neutrophils, and
      keratinocytes after growth in nafcillin. Finally, nafcillin pretreatment ex vivo
      reduced MRSA virulence in a murine subcutaneous infection model. Despite the lack
      of direct activity against MRSA, these studies show potent, consistent, and
      generalized nafcillin-mediated "sensitization" to increased killing of MRSA by
      various components of the innate host response. The use of nafcillin as
      adjunctive therapy in MRSA bacteremia merits further study and should be
      considered in cases refractory to standard therapy. KEY MESSAGES: Nafcillin has
      been used as adjunctive therapy to clear persistent MRSA bacteremia. Nafcillin
      enhances killing of MRSA by a cadre of innate host defense peptides. Nafcillin
      increases binding of human cathelicidin LL-37 to the MRSA membrane. Nafcillin
      enhances killing of MRSA by neutrophils. Nafcillin reduces virulence of MRSA in a
      murine subcutaneous infection model.

PMID- 24297498
TI  - Cardiovascular applications of therapeutic ultrasound.
AB  - Ultrasound (US) has gained widespread use in diagnostic cardiovascular
      applications. At amplitudes and frequencies typical of diagnostic use, its
      biomechanical effects on tissue are largely negligible. However, these parameters
      can be altered to harness US's thermal and non-thermal effects for therapeutic
      indications. High-intensity focused ultrasound (HIFU) and extracorporeal shock
      wave therapy (ECWT) are two therapeutic US modalities which have been
      investigated for treating cardiac arrhythmias and ischemic heart disease,
      respectively. Here, we review the biomechanical effects of HIFU and ECWT, their
      potential therapeutic mechanisms, and pre-clinical and clinical studies
      demonstrating their efficacy and safety limitations. Furthermore, we discuss
      other potential clinical applications of therapeutic US and areas in which future
      research is needed.

PMID- 24297497
TI  - An emerging role of PARK2 in cancer.
AB  - PARK2 (PARKIN) is an E3 ubiquitin ligase involved in multiple signaling pathways
      and cellular processes. Activity of PARK2 is tightly regulated through inter- and
      intra-molecular interactions. Dysfunction of PARK2 is associated with the
      progression of parkinsonism. Notably, frequent PARK2 inactivation has been
      identified in various human cancers. Park2-deficient mice are more susceptible to
      tumorigenesis, indicating its crucial role as a tumor suppressor. However,
      biological studies also show that PARK2 possesses both pro-survival and growth
      suppressive functions. Here, we summarize the genetic lesions of PARK2 in human
      cancers and discuss the current knowledge of PARK2 in cancer progression. We
      further highlight future efforts for the study of PARK2 in cancer. 

PMID- 24297499
TI  - Peripheral neuropathy in ART-experienced patients: prevalence and risk factors.
AB  - Peripheral neuropathy (PN) is a common neurological complication of HIV infection
      that has debilitating effects on quality of life. While there has been a
      comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk
      factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination
      antiretroviral therapy (cART) in ART-naive patients, similar evaluation in ART
      experienced patients is limited. This study investigated the prevalence and RFs
      for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy
      studies. Between February 2000 and June 2007, 522 ART-experienced participants
      who experienced virologic failure with a prior regimen and started new regimens
      were followed longitudinally and annually screened for signs and symptoms of PN.
      Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %,
      respectively. Aging, taller height, protease inhibitor use, and female sex were
      significant RFs for PN/SPN. The use of statin drugs was significantly associated
      with lower odds of SPN, and it may prevent progression from no SPN to SPN.

PMID- 24297500
TI  - Decreased MEG beta oscillations in HIV-infected older adults during the resting
      state.
AB  - The introduction of combination antiretroviral therapy significantly reduced the
      prevalence of the most severe form of HIV-associated neurocognitive disorders
      (HAND). Despite this decline, 35-70 % of HIV-infected patients continue to
      develop mild motor and cognitive impairments. Although neuropsychological studies
      have shown that HAND affects a wide array of cognitive functions, a formal
      diagnosis is still based on the exclusion of opportunistic infections and other
      common ailments, as no specific tests or biomarkers are currently available. In
      this study, we used magnetoencephalography (MEG) to measure neural activity
      during the resting-state in 15 HIV-infected older patients and a demographically
      matched group of 15 uninfected controls. MEG is a noninvasive and direct measure
      of neural activity with excellent spatiotemporal resolution. All MEG data were
      coregistered to structural magnetic resonance images, corrected for head motion,
      fitted to a regional-level source model, and subjected to spectral analyses to
      quantify population-level neural oscillatory activity. We found that HIV-infected
      persons exhibited decreased beta oscillations in the supplementary motor area
      bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of
      the superior parietal lobule relative to healthy controls. Beta oscillations in
      the posterior cingulate, a critical component of the default mode network, were
      also positively correlated with patient scores on the memory recall aspect of the
      Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV
      infection does not uniformly disturb cortical function, and that neuronal
      populations in dorsomedial motor and parietal cortices are especially affected.
      These findings also suggest that resting-state MEG recordings may hold
      significant promise as a functional biomarker for identifying HAND and monitoring
      disease progression.

PMID- 24297501
TI  - Immune surveillance and response to JC virus infection and PML.
AB  - The ubiquitous human polyomavirus JC virus (JCV) is the established etiological
      agent of the debilitating and often fatal demyelinating disease, progressive
      multifocal leukoencephalopathy (PML). Most healthy individuals have been infected
      with JCV and generate an immune response to the virus, yet remain persistently
      infected at subclinical levels. The onset of PML is rare in the general
      population, but has become an increasing concern in immunocompromised patients,
      where reactivation of JCV leads to uncontrolled replication in the CNS.
      Understanding viral persistence and the normal immune response to JCV provides
      insight into the circumstances which could lead to viral resurgence. Further,
      clues on the potential mechanisms of reactivation may be gleaned from the
      crosstalk among JCV and HIV-1, as well as the impact of monoclonal antibody
      therapies used for the treatment of autoimmune disorders, including multiple
      sclerosis, on the development of PML. In this review, we will discuss what is
      known about viral persistence and the immune response to JCV replication in
      immunocompromised individuals to elucidate the deficiencies in viral containment
      that permit viral reactivation and spread. 

PMID- 24297503
TI  - Prospective comparison of computed tomography, diffusion-weighted magnetic
      resonance imaging and [11C]choline positron emission tomography/computed
      tomography for preoperative lymph node staging in prostate cancer patients.
AB  - PURPOSE: The aim of this study was to prospectively compare diffusion-weighted
      magnetic resonance imaging (DWI) and [(11)C]choline positron emission
      tomography/computed tomography (PET/CT) with computed tomography (CT) for
      preoperative lymph node (LN) staging in prostate cancer (PCa) patients. METHODS:
      Between June 2010 and May 2012, CT, DWI and [(11)C]choline PET/CT were performed
      preoperatively in 33 intermediate- and high-risk PCa patients undergoing radical
      prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) including
      obturator fossa and internal, external and common iliac fields. Patient- and
      field-based performance characteristics for all three imaging techniques based on
      histopathological results are reported. Imaging techniques were compared by means
      of the area under the curve (AUC). RESULTS: LN metastases were detected in 92 of
      1,012 (9%) LNs from 14 of 33 (42%) patients. On patient-based analysis,
      sensitivity, specificity and accuracy for CT were 57, 68 and 64%, respectively,
      for DWI were 57, 79 and 70%, respectively, and for [(11)C]choline PET/CT were 57,
      90 and 76%, respectively. On field-based analysis, these numbers for CT were 47,
      94 and 88%, respectively, for DWI were 56, 97 and 92%, respectively, and for
      [(11)C]choline PET/CT were 62, 96 and 92%, respectively. Neither DWI nor
      [(11)C]choline PET/CT performed significantly better than CT on pairwise
      comparison of patient- and field-based results. CONCLUSION: All three imaging
      techniques exhibit a rather low sensitivity with less than two thirds of LN
      metastases being detected on patient- and field-based analysis. Overall
      diagnostic efficacy did not differ significantly between imaging techniques,
      whereas distinct performance characteristics, esp. patient-based specificity,
      were best for [(11)C]choline PET/CT followed by DWI and CT.

PMID- 24297502
TI  - Timing and extent of thyroid surgery for gene carriers of hereditary C cell
      disease--a consensus statement of the European Society of Endocrine Surgeons
      (ESES).
AB  - PURPOSE: This "consensus statement" aims to summarise the current evidence-based
      knowledge as to "timing" and planning the "extent" of thyroid surgery in terms of
      an optimal balance between the prevention of thyroid malignancy (involving
      metastasis) and the risks associated with more extended surgery (permanent
      hypoparathyroidism, permanent paralysis of the recurrent laryngeal nerve).
      Surgery "in time" is influenced by genetic findings and age. Basal (and
      stimulated) calcitonin levels may individualise the timing and extent of surgery.
      MATERIALS AND METHODS: The review of English-language studies addressing the
      management of REarranged during Transfection proto-oncogene mutation carriers
      including the time, extent of thyroid surgery and results. Evidence is mostly
      obtained from well-designed, non-experimental descriptive investigations, such as
      comparative, correlation and case-control studies (level III) with a grading of
      recommendation B, or from expert committee reports or opinions and/or the
      clinical experience of respected authorities (level IV) with a grading of
      recommendation C, respectively. RESULTS: "Risk level D" includes multiple
      endocrine neoplasia 2B cases. Thyroidectomy is recommended within the first year
      of life, preferably as soon as possible, due to the very early transformation of
      C cell hyperplasia to more aggressive tumours. Calcitonin levels may be less
      helpful. In patients with codon 634 mutations (risk level C), thyroidectomy
      between ages 2 and 4 years has been proposed based upon evidence of age-dependent
      and codon-specific progression of early medullary thyroid cancer. In "risk level
      B" (codons 609, 611, 618, 620, 630 and 804), tandem mutation (804-778) patients
      should undergo thyroidectomy before the age of 6 years. "Risk level A" includes
      patients with mutations in codons 321, 515, 533, 600, 603, 606, 635, 649, 666,
      768, 776, 790, 791, 804 (single mutation), 833, 844, 861, 891 or 912. Surgery may
      be postponed until the age of 10 years. However, postponing surgery and avoiding
      central (level VI) neck dissection in patients with risk levels A to C are only
      justified in families with a less aggressive MTC history and in combination with
      the results of basal (and calcium- or pentagastrin-stimulated) serum calcitonin
      levels. The moment of transition from C cell hyperplasia to MTC seems to occur
      when calcitonin levels rise. In patients with normal basal and stimulated
      calcitonin levels, the chance of micro-MTC increases significantly. CONCLUSIONS:
      Hereditary C cell disease acts as a model to apply the results of bedside genetic
      testing, age and calcitonin levels (genotype-age-calcitonin-concept) for the
      individual timing of thyroid surgery and its extent.

PMID- 24297505
TI  - Nuclear imaging in proliferative angiopathy.

PMID- 24297504
TI  - Plasma antioxidants and brain glucose metabolism in elderly subjects with
      cognitive complaints.
AB  - PURPOSE: The role of oxidative stress is increasingly recognized in cognitive
      disorders of the elderly, notably Alzheimer's disease (AD). In these subjects
      brain(18)F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We
      hypothesized that oxidative stress could play a role in impairing brain glucose
      utilization in elderly subjects with increasing severity of cognitive
      disturbance. METHODS: The study group comprised 85 subjects with cognitive
      disturbance of increasing degrees of severity including 23 subjects with
      subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment
      and 34 patients with mild AD. In all subjects brain FDG PET was performed and
      plasma activities of extracellular superoxide dismutase (eSOD), catalase and
      glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to
      compare FDG PET between groups and to evaluate correlations between plasma
      antioxidants and glucose metabolism in the whole group of subjects, correcting
      for age and Mini-Mental State Examination score. RESULTS: Brain glucose
      metabolism progressively decreased in the bilateral posterior temporoparietal and
      cingulate cortices across the three groups, from SCI to mild AD. eSOD activity
      was positively correlated with glucose metabolism in a large area of the left
      temporal lobe including the superior, middle and inferior temporal gyri and the
      fusiform gyrus. CONCLUSION: These results suggest a role of oxidative stress in
      the impairment of glucose utilization in the left temporal lobe structures in
      elderly patients with cognitive abnormalities, including AD and conditions
      predisposing to AD. Further studies exploring the oxidative stress-energy
      metabolism axis are considered worthwhile in larger groups of these patients in
      order to identify pivotal pathophysiological mechanisms and innovative
      therapeutic opportunities.

PMID- 24297506
TI  - Non-antiepileptic drugs for trigeminal neuralgia.
AB  - BACKGROUND: Trigeminal neuralgia was defined by the International Association for
      the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing
      recurrent pain in the distribution of one or more branches of the fifth cranial
      nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs
      have been used in the management of trigeminal neuralgia since the 1970s. This is
      an update of a review first published in 2006 and previously updated in 2011.
      OBJECTIVES: To systematically review the efficacy and tolerability of non
      antiepileptic drugs for trigeminal neuralgia. SEARCH METHODS: On 20 May 2013, for
      this updated review, we searched the Cochrane Neuromuscular Disease Group
      Specialized Register, CENTRAL (2013, Issue 4), MEDLINE (January 1966 to May
      2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013) and
      the Chinese Biomedical Retrieval System (1978 to May 2013). We searched clinical
      trials registries for ongoing trials. SELECTION CRITERIA: We included double
      blind, randomised controlled trials in which the active drug was used either
      alone or in combination with other non-antiepileptic drugs for at least two
      weeks. DATA COLLECTION AND ANALYSIS: Two authors decided which trials fitted the
      inclusion criteria and independently graded risk of bias. We assessed the quality
      of the evidence according to the GRADE criteria for this update. MAIN RESULTS: In
      this 2013 update, we updated the searches, but identified only two new ongoing
      studies. The review includes four trials involving 139 participants. The primary
      outcome measure in each was pain relief. Three trials compared one of the oral
      non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. The
      quality of evidence for all outcomes for which data were available was low. In a
      trial of tizanidine involving 12 participants (one dropped out due to unrelated
      disease), one of five participants treated with tizanidine and four of six
      treated with carbamazepine improved (risk ratio (RR) 0.30, 95% confidence
      interval (CI) 0.05 to 1.89). Few side effects were noted with tizanidine. For
      pimozide, there was evidence of greater efficacy than carbamazepine at six weeks.
      Up to 83% of participants reported adverse effects but these did not lead to
      withdrawal; the report did not provide comparable data for carbamazepine. Limited
      data meant that we could not assess the effects of tocainide; however, data from
      non-randomised studies (not included in this review) indicate that serious
      haematological adverse events can occur. A trial involving 47 participants
      compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show
      any significant benefits, again according to low-quality evidence. The report did
      not mention adverse events. The proparacaine trial was at low risk of bias; the
      other trials were at unclear risk of bias overall. AUTHORS' CONCLUSIONS: There is
      low-quality evidence that the effect of tizanidine is not significantly different
      than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more
      effective than carbamazepine, although the evidence is of low quality and the
      data did not allow comparison of adverse event rates. There is also low-quality
      evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over
      placebo. Limitations in the data for tocainide prevent any conclusions being
      drawn. There is insufficient evidence from randomised controlled trials to show
      significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More
      research is needed.

PMID- 24297507
TI  - Prophylactic versus selective blood transfusion for sickle cell disease in
      pregnancy.
AB  - BACKGROUND: Pregnant women with sickle cell disease (HbSS, HbSC and HbSbetaThal)
      may require blood transfusion to prevent severe anaemia or to manage potential
      medical complications. Preventive blood transfusion in the absence of
      complications starting from the early weeks of pregnancy or blood transfusion
      only for medical or obstetric indications have been used as management policies.
      There is currently no consensus on the blood transfusion policy that guarantees
      optimal clinical benefits with minimal risks for such women and their babies. The
      present review replaces and updates a Cochrane review that was withdrawn in 2006.
      OBJECTIVES: To assess the benefits and harms of a policy of prophylactic versus
      selective blood transfusion in pregnant women with sickle cell disease. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 October 2013) and reference lists of retrieved studies. We did not
      apply any language restrictions. SELECTION CRITERIA: Randomised and quasi
      randomised trials evaluating the effects of prophylactic versus selective
      (emergency) blood transfusion in pregnant women with sickle cell disease. Trials
      were considered for inclusion whether the unit of randomisation was at individual
      or cluster level, however, no cluster-randomised trials were identified. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion and assessed trial quality. Two review authors independently extracted
      data. Data were checked for accuracy. MAIN RESULTS: Out of six relevant reports
      identified by the search strategy, two trials involving 98 women with sickle cell
      anaemia (HbSS) met our inclusion criteria. The two trials were at moderate risk
      of bias. Overall, there were few events for most of the reported outcomes and the
      results were generally imprecise. One trial (involving 72 women) reported no
      maternal mortality occurring in women who received either prophylactic or
      selective blood transfusion. The same trial (involving 72 women) indicated no
      clear differences in maternal mortality, perinatal mortality (risk ratio (RR)
      2.85, 95% confidence interval (CI) 0.61 to 13.22) or markers of severe maternal
      morbidity [pulmonary embolism (no events); congestive cardiac failure (RR 1.00,
      95% CI 0.07 to 15.38); acute chest syndrome (RR 0.67, 95% CI 0.12 to 3.75)]
      between the treatment groups (prophylactic blood transfusion versus selective
      blood transfusion). Prophylactic blood transfusion reduced the risk of pain
      crisis compared with selective blood transfusion (RR 0.42, 95% CI 0.17 to 0.99,
      two trials, 98 women); however, the margin of uncertainty around the effect
      estimate ranged from very small to substantial reduction. One trial (involving 72
      women) indicated no differences in the occurrence of acute splenic sequestration
      (RR 0.33, 95% CI 0.01 to 7.92) and haemolytic crises (RR 0.33, 95% CI 0.04 to
      3.06) and delayed blood transfusion reaction (RR 2.00, 95% CI 0.54 to 7.39)
      between the comparison groups. AUTHORS' CONCLUSIONS: Evidence from two small
      trials of low quality suggests that prophylactic blood transfusion to pregnant
      women with sickle cell anaemia (HbSS) confers no clear clinical benefits when
      compared with selective transfusion. Currently, there is no evidence from
      randomised or quasi-randomised trials to provide reliable advice on the optimal
      blood transfusion policy for women with other variants of sickle cell disease
      (i.e. HbSC and HbSbetaThal). The available data and quality of evidence on this
      subject are insufficient to advocate for a change in existing clinical practice
      and policy.

PMID- 24297509
TI  - Optimal scanning timing by use of multi-detector row computed tomography during
      thoracic aortography for depiction of arteries causing hemoptysis.
AB  - Scanning timing for multi-detector row computed tomography during thoracic
      aortography (MDCT-TA) was explored for depiction of arteries responsible for
      hemoptysis. The mean time (MT) from contrast medium (CM) injection to peak
      enhancement (PE) in the descending aorta at the level of the diaphragm on
      thoracic aortography was investigated. The MT to PE of the descending aorta at
      the level of diaphragm was 4.86 +/- 0.42 s, with 30 mL CM at an injection rate of
      10 mL/s. CM injection was completed 1.86 s before the final slice was obtained.
      The CM injection duration can be calculated as follows: 4.86 s + scan time - 1.86
      s. The optimal scanning timing is a scan delay of approximately 5 s from the
      start of CM injection, and the CM injection duration is expressed as scan time
      plus 3 s. MDCT-TA depicted the branching sites of the bronchial arteries in all
      cases. 

PMID- 24297508
TI  - STAT3 activation in HER2-overexpressing breast cancer promotes epithelial
      mesenchymal transition and cancer stem cell traits.
AB  - Clinically, HER2 proto-oncogene amplification is found in about 25-30% of human
      breast cancers, where it is correlated to a poor prognosis. Constitutive STAT3
      activation is found in about 50-60% of the breast tumors and associated with
      tumorigenesis and drug resistance. In this study, we showed that STAT3 was
      phosphorylated in HER2-overexpressing, ER-positive human breast tumors and,
      furthermore, phosphorylated STAT3 promoted the stem-like cell phenotype. We
      examined the dysregulation of the stem cell markers (Oct-4, Sox-2 and CD44) and
      the tumorsphere formation in HER2-overexpressing human breast cancer cell lines.
      We demonstrated that the STAT3 inhibitor, Stattic, treatment abolished the cancer
      stem cell phenotype in HER2-positive breast cancers. Combined treatment of
      Herceptin and Stattic showed the synergistic effect on the cancer cell growth in
      vitro. In addition, when the STAT3 gene was knocked down, the expression of the
      stem cell markers Oct-4, Sox-2 and CD44 were downregulated and tumorsphere
      formation was abolished. HER2-elicited STAT3 signaling may provide a potential
      model for drug resistance induced by stem-like cell characteristics. This
      mechanism may be responsible for acquiring resistance to Herceptin in the
      treatment of HER2-overexpressing breast tumors. Based on our findings, targeting
      pSTAT3 could overcome Herceptin-induced resistance in HER2-overexpressing breast
      tumors.

PMID- 24297510
TI  - Distinct roles of Akt1 in regulating proliferation, migration and invasion in
      HepG2 and HCT 116 cells.
AB  - Elucidating the effects of genes involved in tumors may improve therapeutic
      strategies for human cancer. Recently, several studies discovered that Akt1 plays
      a dual role in mediating cell proliferation, migration and invasion, depending on
      the cell type. However, the pathophysiological role of Akt1 in hepatocellular
      carcinoma (HCC) and colorectal carcinoma cells remains poorly understood. In the
      present study, we transfected the Akt1-expressing plasmids into the tumor cells
      that expressed only low levels of Akt1. The migration and invasion abilities were
      analyzed in 24-well Boyden chambers. The expression of proteins was detected
      using western blot analysis. Our results demonstrated that overexpression of Akt1
      significantly enhanced the proliferation rates and promoted the colony formation
      in both HepG2 and HCT 116 cells. When treated with wortmannin, the ability to
      form colonies was significantly attenuated in both cell lines. Of note, enforced
      expression of Akt1 induced HepG2 cell migration and invasion; by contrast,
      upregulation of Akt1 expression suppressed the migration and invasion of HCT 116
      cells. Subsequent mechanistic investigations revealed that upregulation of Akt1
      markedly induced the expression of Bcl-2 and NF-kappaB in both types of tumor
      cells. Notably, we observed a similar increase of MMP2, MMP9, HIF1alpha and VEGF
      in HCC cells, whereas Akt1 significantly suppressed the expression of these
      molecules in colorectal carcinoma cells. These data suggest a dual role for Akt1
      in tumor cell migration and invasion and highlight the cell type-specific actions
      of Akt1 kinases in the regulation of cell motility. 

PMID- 24297511
TI  - [Radiological findings of the nasal septum in CT scan in patients with deviated
      noses].
AB  - OBJECTIVE: The bony-cartilaginous crooked nose is characterized by a deviation of
      the nasal dorsum from the median sagittal plane. Since the nasal dorsum and the
      septum form an anatomical entity, a deviation of the external nose always results
      in a deviation of the cartilaginous and bony nasal septum. The aim of this study
      was to analyze the pathologies of the septum in patients with crooked noses based
      on CT images of the midface. METHODS: The CT images of patients with a documented
      crooked nose, who presented between 2005 and 2011 in our hospital, were analyzed
      retrospectively considering photo documentation and nasal findings. The CT scans
      were performed due to suspected sinusitis unrelated to the study. RESULTS: The
      study includes a total of 138 patients. In all patients a deviated septum was
      found in the CT. In particular, there was not only a deviation of the
      cartilaginous septum, but also a deviation of the perpendicular plate (PP) in 86%
      of the cases. This PP deviation distorted to the opposite side of the deviation
      of the crooked nose in 79% of the cases. However, the base of the PP at the
      cribriform plate was in a median position in 99% of the cases of the patients.
      Furthermore, in 96% of cases, the caudal septum was located in midline on the
      anterior nasal spine, -although 15% presented clinically a dislocation of the
      caudal septum. CONCLUSIONS: The bony-cartilaginous crooked nose usually results
      in a deviation of the cartilaginous and bony septum. In particular, a high
      deviation of the PP to the opposite side of the deviation of the external nose
      was present in a majority of the -cases. Therefore, a septo-rhinoplasty with
      particular consideration of the deviation of the PP is necessary in patients with
      a deviated external nose.

PMID- 24297512
TI  - The effect of time delay in a two-patch model with random dispersal.
AB  - We consider a two-patch model for a single species with dispersal and time delay.
      For some explicit range of dispersal rates, we show that there exists a critical
      value tauc for the time delay tau such that the unique positive equilibrium of
      the system is locally asymptotically stable for tau ?[0,tauc) and unstable for
      tau > tauc .

PMID- 24297513
TI  - Properties and in vitro characterization of polyhydroxybutyrate-chitosan
      scaffolds prepared by modified precipitation method.
AB  - Porous polyhydroxybutyrate (PHB)-chitosan biopolymer scaffolds were prepared by
      co-precipitation from biopolymer solutions with propylene carbonate and acetic
      acid as solvents. A change of the fibrous character of chitosan precipitates to
      globular shaped forms with a polyhydroxybutyrate addition was found in
      suspensions. Scaffolds differ by porosity and morphology of polymers in
      microstructures, while chitosan represented more compact plate-like fibers and
      PHB characterized mainly fine fibrous globular agglomerates. Two structurally
      dissimilar phase regions were verified in blended scaffolds. A rise in the number
      of smaller pores, and fine structured polymer forms with PHB content were
      observed in the scaffolds. A significant reduction in the average molecular
      weight of biopolymers was found in pure chitosan scaffold, this after
      precipitation of the chitosan in the presence of propylene carbonate and in
      blends after mutual biopolymer mixing. Interactions between shortened chitosan
      chains, PHB and chitosan biopolymers in the blends were observed. An excellent
      fibroblast proliferation was found in scaffolds prepared from biopolymer blends. 

PMID- 24297514
TI  - Towards ready-to-use 3-D scaffolds for regenerative medicine: adhesion-based
      cryopreservation of human mesenchymal stem cells attached and spread within
      alginate-gelatin cryogel scaffolds.
AB  - Cultivation and proliferation of stem cells in three-dimensional (3-D) scaffolds
      is a promising strategy for regenerative medicine. Mesenchymal stem cells with
      their potential to differentiate in various cell types, cryopreserved adhesion
      based in fabricated scaffolds of biocompatible materials can serve as ready-to
      use transplantation units for tissue repair, where pores allow a direct contact
      of graft cells and recipient tissue without further preparation. A successful
      cryopreservation of adherent cells depends on attachment and spreading processes
      that start directly after cell seeding. Here, we analyzed different cultivation
      times (0.5, 2, 24 h) prior to adhesion-based cryopreservation of human
      mesenchymal stem cells within alginate-gelatin cryogel scaffolds and its
      influence on cell viability, recovery and functionality at recovery times (0, 24,
      48 h) in comparison to non-frozen control. Analysis with confocal laser scanning
      microscopy and scanning electron microscopy indicated that 2 h cultivation time
      enhanced cryopreservation success: cell number, visual cell contacts, membrane
      integrity, motility, as well as spreading were comparable to control. In
      contrast, cell number by short cultivation time (0.5 h) reduced dramatically
      after thawing and expanded cultivation time (24 h) decreased cell viability. Our
      results provide necessary information to enhance the production and to store
      ready-to-use transplantation units for application in bone, cartilage or skin
      regenerative therapy. 

PMID- 24297516
TI  - Evaluation of the sufficiency of pedicled temporoparietal fascial flap on rat
      head and neck defects: detailed anatomical study.
AB  - The temporoparietal flap containing the temporal fascia has a wide spectrum of
      applications in head and neck surgery. The aim of this study is to demonstrate a
      temporoparietal fascial flap model that can be used in various head and neck
      defects in rats. Ten male Sprague-Dawley rats weighing 250-300 g were used in
      this study. Temporoparietal fascial flaps were elevated with the axial pedicle
      from the rats using microsurgical techniques. The arc rotations of the flaps on
      the pedicles were examined and the dimensions of the defects these flaps could
      cover were identified. The flaps were observed to be the right size for use with
      defects of the occipital, temporal and mastoid regions, ear, facial nerve and the
      mandible. The temporoparietal fascial flap is an experimental flap model, which
      can be useful in experimental studies related to complex head and neck defects. 

PMID- 24297515
TI  - Salt adaptation requires efficient fine-tuning of jasmonate signalling.
AB  - Understanding the mechanism by which plants sense, signal and respond to salinity
      stress is of great interest to plant biologists. In stress signalling, often the
      same molecules are involved in both damage-related and adaptive events. To
      dissect this complexity, we compared the salinity responses of two grapevine cell
      lines differing in their salinity tolerance. We followed rapid changes in the
      cellular content of sodium and calcium, apoplastic alkalinisation and slower
      responses in the levels of jasmonic acid, its active isoleucine conjugate and
      abscisic acid, as well as of stilbenes. Differences in timing and sensitivity to
      either the lanthanoid Gd or exogenous calcium provide evidence for an adaptive
      role of early sodium uptake through non-selective cation channels acting upstream
      of Ca(2+) and H(+) fluxes. We find a correlation of salt sensitivity with
      unconstrained jasmonate (JA) signalling, whereas salt adaptation correlates with
      tight control of jasmonic acid and its isoleucine conjugate, accompanied by
      accumulation of abscisic acid and suppression of stilbenes that trigger defence
      related cell death. The data are discussed by a model where efficient fine-tuning
      of JA signalling determines whether cells will progress towards adaptation or
      programme cell death. 

PMID- 24297517
TI  - Measuring food and nutrition security: tools and considerations for use among
      people living with HIV.
AB  - As an increasing number of countries implement integrated food and nutrition
      security (FNS) and HIV programs, global stakeholders need clarity on how to best
      measure FNS at the individual and household level. This paper reviews prominent
      FNS measurement tools, and describes considerations for interpretation in the
      context of HIV. There exist a range of FNS measurement tools and many have been
      adapted for use in HIV-endemic settings. Considerations in selecting appropriate
      tools include sub-types (food sufficiency, dietary diversity and food safety);
      scope/level of application; and available resources. Tools need to reflect both
      the needs of PLHIV and affected households and FNS program objectives.
      Generalized food sufficiency and dietary diversity tools may provide adequate
      measures of FNS in PLHIV for programmatic applications. Food consumption
      measurement tools provide further data for clinical or research applications.
      Measurement of food safety is an important, but underdeveloped aspect of
      assessment, especially for PLHIV. 

PMID- 24297518
TI  - LipidGO: database for lipid-related GO terms and applications.
AB  - MOTIVATION: Lipid, an essential class of biomolecules, is receiving increasing
      attention in the research community, especially with the development of
      analytical technique like mass spectrometry. Gene Ontology (GO) is the de facto
      standard function annotation scheme for gene products. Identification of both
      explicit and implicit lipid-related GO terms will help lipid research in many
      ways, e.g. assigning lipid function in protein function prediction. RESULTS: We
      have constructed a Web site 'LipidGO' that facilitates browsing and searching
      lipid-related GO terms. An expandable hierarchical GO tree is constructed that
      allows users to find lipid-related GO terms easily. To support large-scale
      analysis, a user is able to upload a list of gene products or a list of GO terms
      to find out which of them is lipid related. Finally, we demonstrate the
      usefulness of 'LipidGO' by two applications: (i) identifying lipid-related gene
      products in model organisms and (ii) discovering potential novel lipid-related
      molecular functions AVAILABILITY AND IMPLEMENTATION: LipidGO is available at
      http://compbio.ddns.comp.nus.edu.sg/%7elipidgo/index.php.

PMID- 24297519
TI  - Topological augmentation to infer hidden processes in biological systems.
AB  - MOTIVATION: A common problem in understanding a biochemical system is to infer
      its correct structure or topology. This topology consists of all relevant state
      variables-usually molecules and their interactions. Here we present a method
      called topological augmentation to infer this structure in a statistically
      rigorous and systematic way from prior knowledge and experimental data. RESULTS:
      Topological augmentation starts from a simple model that is unable to explain the
      experimental data and augments its topology by adding new terms that capture the
      experimental behavior. This process is guided by representing the uncertainty in
      the model topology through stochastic differential equations whose trajectories
      contain information about missing model parts. We first apply this semiautomatic
      procedure to a pharmacokinetic model. This example illustrates that a global
      sampling of the parameter space is critical for inferring a correct model
      structure. We also use our method to improve our understanding of glutamine
      transport in yeast. This analysis shows that transport dynamics is determined by
      glutamine permeases with two different kinds of kinetics. Topological
      augmentation can not only be applied to biochemical systems, but also to any
      system that can be described by ordinary differential equations. AVAILABILITY AND
      IMPLEMENTATION: Matlab code and examples are available at:
      http://www.csb.ethz.ch/tools/index

PMID- 24297520
TI  - NextClip: an analysis and read preparation tool for Nextera Long Mate Pair
      libraries.
AB  - SUMMARY: Illumina's recently released Nextera Long Mate Pair (LMP) kit enables
      production of jumping libraries of up to 12 kb. The LMP libraries are an
      invaluable resource for carrying out complex assemblies and other downstream
      bioinformatics analyses such as the characterization of structural variants.
      However, LMP libraries are intrinsically noisy and to maximize their value, post
      sequencing data analysis is required. Standardizing laboratory protocols and the
      selection of sequenced reads for downstream analysis are non-trivial tasks.
      NextClip is a tool for analyzing reads from LMP libraries, generating a
      comprehensive quality report and extracting good quality trimmed and deduplicated
      reads. AVAILABILITY AND IMPLEMENTATION: Source code, user guide and example data
      are available from https://github.com/richardmleggett/nextclip/.

PMID- 24297522
TI  - Breaking the silence: functional expression of the two-pore-domain potassium
      channel THIK-2.
AB  - THIK-2 belongs to the 'silent' channels of the two-pore-domain potassium channel
      family. It is highly expressed in many nuclei of the brain but has so far
      resisted all attempts at functional expression. THIK-2 has a highly conserved 19
      amino-acid region in its N terminus (residues 6-24 in the rat orthologue) that is
      missing in the closely related channel THIK-1. After deletion of this region
      (THIK-2(Delta6-24) mutant), functional expression of the channel was observed in
      Xenopus oocytes and in mammalian cell lines. The resulting potassium current
      showed outward rectification under physiological conditions and slight inward
      rectification with symmetrical high-K(+) solutions and could be inhibited by
      application of halothane or quinidine. Another THIK-2 mutant, in which the
      putative retention/retrieval signal RRR at positions 14-16 was replaced by AAA,
      produced a similar potassium current. Both mutants showed a distinct localisation
      to the surface membrane when tagged with green fluorescent protein and expressed
      in a mammalian cell line, whereas wild-type THIK-2 was mainly localised to the
      endoplasmic reticulum. These findings suggest that deletion of the
      retention/retrieval signal RRR enabled transport of THIK-2 channels to the
      surface membrane. Combining the mutation THIK-2(Delta6-24) with a mutation in the
      pore cavity (rat THIK-2(I158G)) gave rise to a 12-fold increase in current
      amplitude, most likely due to an increase in open probability. In conclusion, the
      characteristics of THIK-2 channels can be analysed in heterologous expression
      systems by using trafficking and/or gating mutants. The possible mechanisms that
      enable THIK-2 expression at the surface membrane in vivo remain to be determined.

PMID- 24297523
TI  - Development of a validated stability-indicating HPTLC method for rufinamide in
      bulk and its pharmaceutical dosage form.
AB  - A sensitive, selective, precise and stability indicating a high-performance thin
      layer chromatographic method for the analysis of rufinamide (Rf) in bulk drug and
      its formulations was developed and validated. The method employed thin layer
      chromatography aluminum plates precoated with silica gel 60 F254 as the
      stationary phase. The solvent system consisted of chloroform : methanol : glacial
      acetic acid (9 : 1 : 0.1 v/v/v). This system was found to give compact spots for
      Rf (Rf value of 0.68 +/- 0.02). Rf was subjected to acid and alkali hydrolysis,
      oxidation, photodegradation and dry heat treatment. Also, the degraded products
      were well separated from the pure drug. Densitometric analysis of Rf was carried
      out in the absorbance mode at 210 nm, which is wavelength maxima for the
      degradant. The linear regression data for the calibration plots showed a good
      linear relationship with an r(2) of 0.9989 in the concentration range of 1,000
      3,500 ng. The method was validated for precision, accuracy, ruggedness and
      recovery. The limits of detection and quantitation were 196.59 and 595.74 ng
      spot(-1), respectively. The drug undergoes degradation under acidic and basic
      conditions. All the peaks of degraded products were resolved from the standard
      drug with significantly different Rf values.

PMID- 24297524
TI  - Stability-indicating LC method for the simultaneous determination of lisinopril
      and hydrochlorothiazide.
AB  - A simple and rapid stability-indicating liquid chromatographic method was
      developed and validated for the simultaneous determination of lisinopril and
      hydrochlorotiazide (HCTZ) in drug substances and dosage forms in the presence of
      degradation products. Forced degradation studies were conducted on the pure drugs
      under hydrolytic, oxidative, thermal and photolytic conditions. A chromatographic
      separation of the two drugs and its degradation products was achieved with an RP
      18 column, using methanol, acetonitrile and phosphate buffer (pH 7.1; 0.05 M)
      (15:15:70, v/v/v) as mobile phase at a flow rate of 0.8 mL min(-1) and UV
      detection at 210 nm. Lisinopril and HCTZ were well resolved from its degradation
      products showing the stability-indicating capability of the method. The described
      method was linear over a range of 40-200 ug mL(-1) for lisinopril and 25-175 ug
      mL(-1) for HCTZ. The assay was also selective, accurate and precise for
      lisinopril and HCTZ determination. This method represents an alternative to the
      United States Pharmacopeia (USP) method showing shorter retention time. The
      method was successfully applied for determination of lisinopril and HCTZ in
      combined commercial tablets. The results showed that the proposed method was
      found to be suitable for quantitative determination and the stability study of
      lisinopril and HCTZ in pharmaceutical samples. 

PMID- 24297525
TI  - Determination of parabens in beverage samples by dispersive liquid-liquid
      microextraction based on solidification of floating organic droplet.
AB  - A simple and efficient method for dispersive liquid-liquid microextraction of
      methylparaben, ethylparaben, propylparaben and butylparaben in real beverage
      samples was developed. It is making use of solidified floating organic droplets
      of 1-dodecanol which has low density and a proper melting point. Parameters
      influencing the extraction efficiency, such as the type of extraction and
      dispersive solvent, the volume of extraction and dispersive solvent, salt effect,
      pH, extraction time, were optimized and resulted in enrichment factors (EFs) of
      84 for methylparaben, 103 for ethylparaben, 115 for propylparaben and 126 for
      butylparaben. The limits of detection for parabens were 1.52, 1.06, 0.32 and 0.17
      ng/mL, respectively. Excellent linearity with coefficients of correlation from
      0.9970 to 0.9997 was observed in the concentration range of 5-1,000 ng/mL. The
      repeatability of the proposed method expressed as relative standard deviations
      (RSDs) ranged from 2.54 to 3.89% (n = 5). The relative recoveries for parabens in
      beverage samples were good and in the ranges of 89.8-109.9, 90.2-107.3, 90.9
      101.7 and 92.3-118.1%, respectively. Thus, the proposed method has excellent
      potential for the determination of parabens in beverage samples.

PMID- 24297526
TI  - Simultaneous determination of tramadol and O-desmethyltramadol in human plasma
      using HPLC-DAD.
AB  - A sensitive and accurate method for the extraction and quantification of tramadol
      (T) and its active metabolite, O-desmethyltramadol (ODT) in human plasma with
      high-performance liquid chromatography-diode array detection was developed and
      validated. The analytes were extracted from plasma samples by tert-butylmethyl
      ether in the presence of ammonium hydroxide as alkaline medium and back
      extraction with 1.0 M hydrochloric acid. Propranolol was used as internal
      standard. The extraction efficiencies of T and ODT were 83.51 and 78.72%,
      respectively. The calibration curves were linear (r(2) > 0.99) in the
      concentration range of 250-2000 ng/mL for T and ODT. Limits of detection and
      quantification were 125 and 250 ng/mL for both analytes. Intra- and interassay
      precision for T and ODT were ranged from 1.89 to 10.91% and 2.16 to 5.85%,
      respectively. Intra- and interassay accuracy for T and ODT were ranged from 
      13.07 to 4.99% and -2.03 to -6.98%, respectively. The method was successfully
      applied to quantify T and ODT from authentic plasma samples received from
      Hospital Sohag University. The method was completely validated and can be of
      interest to clinical and forensic laboratories.

PMID- 24297527
TI  - Prolonged androgen deprivation leads to overexpression of calpain 2: implications
      for prostate cancer progression.
AB  - Understanding the molecular mechanism of prostate cancer progression from
      androgen dependence to independence may lead to developing more effective
      treatments against prostate cancer. Herein, our previous in vitro model was
      employed to assess the effects of continuous androgen-deprivation on developing
      the metastatic phenotype from androgen-dependent prostate cancer cells (LNCaP).
      The results indicated that long-term androgen deprivation resulted in
      overexpression of calpain 2 and increased expression of filamin A (FlnA), but not
      for calpain 1. The enhanced activity of calpain 2 was confirmed by the
      accumulation of cleaved FlnA fragments, which could be effectively blocked by
      calpeptin (an inhibitor of calpain 2). Therefore, the combination of calpain 2
      inhibitor and androgen deprivation may provide new therapeutic strategy for
      patients to prevent or postpone prostate cancer progression.

PMID- 24297529
TI  - Tumor haplotype assembly algorithms for cancer genomics.
AB  - The growing availability of inexpensive high-throughput sequence data is enabling
      researchers to sequence tumor populations within a single individual at high
      coverage. But, cancer genome sequence evolution and mutational phenomena like
      driver mutations and gene fusions are difficult to investigate without first
      reconstructing tumor haplotype sequences. Haplotype assembly of single individual
      tumor populations is an exceedingly difficult task complicated by tumor haplotype
      heterogeneity, tumor or normal cell sequence contamination, polyploidy, and
      complex patterns of variation. While computational and experimental haplotype
      phasing of diploid genomes has seen much progress in recent years, haplotype
      assembly in cancer genomes remains uncharted territory. In this work, we describe
      HapCompass-Tumor a computational modeling and algorithmic framework for haplotype
      assembly of copy number variable cancer genomes containing haplotypes at
      different frequencies and complex variation. We extend our polyploid haplotype
      assembly model and present novel algorithms for (1) complex variations, including
      copy number changes, as varying numbers of disjoint paths in an associated graph,
      (2) variable haplotype frequencies and contamination, and (3) computation of
      tumor haplotypes using simple cycles of the compass graph which constrain the
      space of haplotype assembly solutions. The model and algorithm are implemented in
      the software package HapCompass-Tumor which is available for download from
      http://www.brown.edu/Research/Istrail_Lab/. 

PMID- 24297530
TI  - Extracting significant sample-specific cancer mutations using their protein
      interactions.
AB  - We present a joint analysis method for mutation and gene expression data
      employing information about proteins that are highly interconnected at the level
      of protein to protein (pp) interactions, which we apply to the TCGA Acute Myeloid
      Leukemia (AML) dataset. Given the low incidence of most mutations in virtually
      all cancer types, as well as the significant inter-patient heterogeneity of the
      mutation landscape, determining the true causal mutations in each individual
      patient remains one of the most important challenges for personalized cancer
      diagnostics and therapy. More automated methods are needed for determining these
      "driver" mutations in each individual patient. For this purpose, we are
      exploiting two types of contextual information: (1) the pp interactions of the
      mutated genes, as well as (2) their potential correlations with gene expression
      clusters. The use of pp interactions is based on our surprising finding that most
      AML mutations tend to affect nontrivial protein to protein interaction cliques. 

PMID- 24297531
TI  - The Stream algorithm: computationally efficient ridge-regression via Bayesian
      model averaging, and applications to pharmacogenomic prediction of cancer cell
      line sensitivity.
AB  - Computational efficiency is important for learning algorithms operating in the
      "large p, small n" setting. In computational biology, the analysis of data sets
      containing tens of thousands of features ("large p"), but only a few hundred
      samples ("small n"), is nowadays routine, and regularized regression approaches
      such as ridge-regression, lasso, and elastic-net are popular choices. In this
      paper we propose a novel and highly efficient Bayesian inference method for
      fitting ridge-regression. Our method is fully analytical, and bypasses the need
      for expensive tuning parameter optimization, via cross-validation, by employing
      Bayesian model averaging over the grid of tuning parameters. Additional
      computational efficiency is achieved by adopting the singular value decomposition
      reparametrization of the ridge-regression model, replacing computationally
      expensive inversions of large p * p matrices by efficient inversions of small and
      diagonal n * n matrices. We show in simulation studies and in the analysis of two
      large cancer cell line data panels that our algorithm achieves slightly better
      predictive performance than cross-validated ridge-regression while requiring only
      a fraction of the computation time. Furthermore, in comparisons based on the cell
      line data sets, our algorithm systematically out-performs the lasso in both
      predictive performance and computation time, and shows equivalent predictive
      performance, but considerably smaller computation time, than the elastic-net. 

PMID- 24297532
TI  - Sharing information to reconstruct patient-specific pathways in heterogeneous
      diseases.
AB  - Advances in experimental techniques resulted in abundant genomic, transcriptomic,
      epigenomic, and proteomic data that have the potential to reveal critical drivers
      of human diseases. Complementary algorithmic developments enable researchers to
      map these data onto protein-protein interaction networks and infer which
      signaling pathways are perturbed by a disease. Despite this progress, integrating
      data across different biological samples or patients remains a substantial
      challenge because samples from the same disease can be extremely heterogeneous.
      Somatic mutations in cancer are an infamous example of this heterogeneity.
      Although the same signaling pathways may be disrupted in a cancer patient cohort,
      the distribution of mutations is long-tailed, and many driver mutations may only
      be detected in a small fraction of patients. We developed a computational
      approach to account for heterogeneous data when inferring signaling pathways by
      sharing information across the samples. Our technique builds upon the prize
      collecting Steiner forest problem, a network optimization algorithm that extracts
      pathways from a protein-protein interaction network. We recover signaling
      pathways that are similar across all samples yet still reflect the unique
      characteristics of each biological sample. Leveraging data from related tumors
      improves our ability to recover the disrupted pathways and reveals patient
      specific pathway perturbations in breast cancer. 

PMID- 24297533
TI  - Detecting statistical interaction between somatic mutational events and germline
      variation from next-generation sequence data.
AB  - The two-hit model of carcinogenesis provides a valuable framework for
      understanding the role of DNA repair and tumor suppressor genes in cancer
      development and progression. Under this model, tumor development can initiate
      from a single somatic mutation in individuals that inherit an inactivating
      germline variant. Although the two-hit model can be an overgeneralization, the
      tendency for the pattern of somatic mutations to differ in cancer patients that
      inherit predisposition alleles is a signal that can be used to identify and
      validate germline susceptibility variants. Here, we present the Somatic-Germline
      Interaction (SGI) tool, which is designed to identify statistical interaction
      between germline variants and somatic mutational events from next-generation
      sequence data. SGI interfaces with rare-variant association tests and variant
      classifiers to identify candidate germline susceptibility variants from case
      control sequencing data. SGI then analyzes tumor-normal pair next-generation
      sequence data to evaluate evidence for somatic-germline interaction in each gene
      or pathway using two tests: the Allelic Imbalance Rank Sum (AIRS) test and the
      Somatic Mutation Interaction Test (SMIT). AIRS tests for preferential allelic
      imbalance to evaluate whether somatic mutational events tend to amplify candidate
      germline variants. SMIT evaluates whether somatic point mutations and small
      indels occur more or less frequently than expected in the presence of candidate
      germline variants. Both AIRS and SMIT control for heterogeneity in the mutational
      process resulting from regional variation in mutation rates and inter-sample
      variation in background mutation rates. The SGI test combines AIRS and SMIT to
      provide a single, unified measure of statistical interaction between somatic
      mutational events and germline variation. We show that the tests implemented in
      SGI have high power with relatively modest sample sizes in a wide variety of
      scenarios. We demonstrate the utility of SGI to increase the power of rare
      variant association studies in cancer and to validate the potential role in
      cancer causation of germline susceptibility variants. 

PMID- 24297534
TI  - Systematic assessment of analytical methods for drug sensitivity prediction from
      cancer cell line data.
AB  - Large-scale pharmacogenomic screens of cancer cell lines have emerged as an
      attractive pre-clinical system for identifying tumor genetic subtypes with
      selective sensitivity to targeted therapeutic strategies. Application of modern
      machine learning approaches to pharmacogenomic datasets have demonstrated the
      ability to infer genomic predictors of compound sensitivity. Such modeling
      approaches entail many analytical design choices; however, a systematic study
      evaluating the relative performance attributable to each design choice is not yet
      available. In this work, we evaluated over 110,000 different models, based on a
      multifactorial experimental design testing systematic combinations of modeling
      factors within several categories of modeling choices, including: type of
      algorithm, type of molecular feature data, compound being predicted, method of
      summarizing compound sensitivity values, and whether predictions are based on
      discretized or continuous response values. Our results suggest that model input
      data (type of molecular features and choice of compound) are the primary factors
      explaining model performance, followed by choice of algorithm. Our results also
      provide a statistically principled set of recommended modeling guidelines,
      including: using elastic net or ridge regression with input features from all
      genomic profiling platforms, most importantly, gene expression features, to
      predict continuous-valued sensitivity scores summarized using the area under the
      dose response curve, with pathway targeted compounds most likely to yield the
      most accurate predictors. In addition, our study provides a publicly available
      resource of all modeling results, an open source code base, and experimental
      design for researchers throughout the community to build on our results and
      assess novel methodologies or applications in related predictive modeling
      problems. 

PMID- 24297536
TI  - An integrated approach to blood-based cancer diagnosis and biomarker discovery.
AB  - Disrupted or abnormal biological processes responsible for cancers often
      quantitatively manifest as disrupted additive and multiplicative interactions of
      gene/protein expressions correlating with cancer progression. However, the
      examination of all possible combinatorial interactions between gene features in
      most case-control studies with limited training data is computationally
      infeasible. In this paper, we propose a practically feasible data integration
      approach, QUIRE (QUadratic Interactions among infoRmative fEatures), to identify
      discriminative complex interactions among informative gene features for cancer
      diagnosis and biomarker discovery directly based on patient blood samples. QUIRE
      works in two stages, where it first identifies functionally relevant gene groups
      for the disease with the help of gene functional annotations and available
      physical protein interactions, then it explores the combinatorial relationships
      among the genes from the selected informative groups. Based on our private
      experimentally generated data from patient blood samples using a novel SOMAmer
      (Slow Off-rate Modified Aptamer) technology, we apply QUIRE to cancer diagnosis
      and biomarker discovery for Renal Cell Carcinoma (RCC) and Ovarian Cancer (OVC).
      To further demonstrate the general applicability of our approach, we also apply
      QUIRE to a publicly available Colorectal Cancer (CRC) dataset that can be used to
      prioritize our SOMAmer design. Our experimental results show that QUIRE
      identifies gene-gene interactions that can better identify the different cancer
      stages of samples, as compared to other state-of-the-art feature selection
      methods. A literature survey shows that many of the interactions identified by
      QUIRE play important roles in the development of cancer. 

PMID- 24297535
TI  - Integrative analysis of two cell lines derived from a non-small-lung cancer
      patient--a panomics approach.
AB  - Cancer cells derived from different stages of tumor progression may exhibit
      distinct biological properties, as exemplified by the paired lung cancer cell
      lines H1993 and H2073. While H1993 was derived from chemo-naive metastasized
      tumor, H2073 originated from the chemo-resistant primary tumor from the same
      patient and exhibits strikingly different drug response profile. To understand
      the underlying genetic and epigenetic bases for their biological properties, we
      investigated these cells using a wide range of large-scale methods including
      whole genome sequencing, RNA sequencing, SNP array, DNA methylation array, and de
      novo genome assembly. We conducted an integrative analysis of both cell lines to
      distinguish between potential driver and passenger alterations. Although many
      genes are mutated in these cell lines, the combination of DNA- and RNA-based
      variant information strongly implicates a small number of genes including TP53
      and STK11 as likely drivers. Likewise, we found a diverse set of genes
      differentially expressed between these cell lines, but only a fraction can be
      attributed to changes in DNA copy number or methylation. This set included the
      ABC transporter ABCC4, implicated in drug resistance, and the metastasis
      associated MET oncogene. While the rich data content allowed us to reduce the
      space of hypotheses that could explain most of the observed biological
      properties, we also caution there is a lack of statistical power and inherent
      limitations in such single patient case studies. 

PMID- 24297537
TI  - Multiplex meta-analysis of medulloblastoma expression studies with external
      controls.
AB  - We propose and discuss a method for doing gene expression meta-analysis (multiple
      datasets) across multiplex measurement modalities measuring the expression of
      many genes simultaneously (e.g. microarrays and RNAseq) using external control
      samples and a method of heterogeneity detection to identify and filter on
      comparable gene expression measurements. We demonstrate this approach on publicly
      available gene expression datasets from samples of medulloblastoma and normal
      cerebellar tissue and identify some potential new targets in the treatment of
      medulloblastoma. 

PMID- 24297539
TI  - Challenges in secondary analysis of high throughput screening data.
AB  - Repurposing an existing drug for an alternative use is not only a cost effective
      method of development, but also a faster process due to the drug's previous
      clinical testing and established pharmokinetic profiles. A potentially rich
      resource for computational drug repositioning approaches is publically available
      high throughput screening data, available in databases such as PubChem Bioassay
      and ChemBank. We examine statistical and computational considerations for
      secondary analysis of publicly available high throughput screening (HTS) data
      with respect to metadata, data quality, and completeness. We discuss developing
      methods and best practices that can help to ameliorate these issues. 

PMID- 24297540
TI  - Drug Intervention Response Predictions with PARADIGM (DIRPP) identifies drug
      resistant cancer cell lines and pathway mechanisms of resistance.
AB  - The revolution in sequencing techniques in the past decade has provided an
      extensive picture of the molecular mechanisms behind complex diseases such as
      cancer. The Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Project
      (CGP) have provided an unprecedented opportunity to examine copy number, gene
      expression, and mutational information for over 1000 cell lines of multiple tumor
      types alongside IC50 values for over 150 different drugs and drug related
      compounds. We present a novel pipeline called DIRPP, Drug Intervention Response
      Predictions with PARADIGM7, which predicts a cell line's response to a drug
      intervention from molecular data. PARADIGM (Pathway Recognition Algorithm using
      Data Integration on Genomic Models) is a probabilistic graphical model used to
      infer patient specific genetic activity by integrating copy number and gene
      expression data into a factor graph model of a cellular network. We evaluated the
      performance of DIRPP on endometrial, ovarian, and breast cancer related cell
      lines from the CCLE and CGP for nine drugs. The pipeline is sensitive enough to
      predict the response of a cell line with accuracy and precision across datasets
      as high as 80 and 88% respectively. We then classify drugs by the specific
      pathway mechanisms governing drug response. This classification allows us to
      compare drugs by cellular response mechanisms rather than simply by their
      specific gene targets. This pipeline represents a novel approach for predicting
      clinical drug response and generating novel candidates for drug repurposing and
      repositioning. 

PMID- 24297541
TI  - Anti-infectious drug repurposing using an integrated chemical genomics and
      structural systems biology approach.
AB  - The emergence of multi-drug and extensive drug resistance of microbes to
      antibiotics poses a great threat to human health. Although drug repurposing is a
      promising solution for accelerating the drug development process, its application
      to anti-infectious drug discovery is limited by the scope of existing phenotype-,
      ligand-, or target-based methods. In this paper we introduce a new computational
      strategy to determine the genome-wide molecular targets of bioactive compounds in
      both human and bacterial genomes. Our method is based on the use of a novel
      algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map
      the chemical universe to its global pharmacological space. ligENTS outperforms
      the state-of-the-art algorithms in identifying novel drug-target relationships.
      Furthermore, we integrate ligENTS with our structural systems biology platform to
      identify drug repurposing opportunities via target similarity profiling. Using
      this integrated strategy, we have identified novel P. falciparum targets of drug
      like active compounds from the Malaria Box, and suggest that a number of approved
      drugs may be active against malaria. This study demonstrates the potential of an
      integrative chemical genomics and structural systems biology approach to drug
      repurposing. 

PMID- 24297542
TI  - Drug-target interaction prediction by integrating chemical, genomic, functional
      and pharmacological data.
AB  - In silico prediction of unknown drug-target interactions (DTIs) has become a
      popular tool for drug repositioning and drug development. A key challenge in DTI
      prediction lies in integrating multiple types of data for accurate DTI
      prediction. Although recent studies have demonstrated that genomic, chemical and
      pharmacological data can provide reliable information for DTI prediction, it
      remains unclear whether functional information on proteins can also contribute to
      this task. Little work has been developed to combine such information with other
      data to identify new interactions between drugs and targets. In this paper, we
      introduce functional data into DTI prediction and construct biological space for
      targets using the functional similarity measure. We present a probabilistic
      graphical model, called conditional random field (CRF), to systematically
      integrate genomic, chemical, functional and pharmacological data plus the
      topology of DTI networks into a unified framework to predict missing DTIs. Tests
      on two benchmark datasets show that our method can achieve excellent prediction
      performance with the area under the precision-recall curve (AUPR) up to 94.9.
      These results demonstrate that our CRF model can successfully exploit
      heterogeneous data to capture the latent correlations of DTIs, and thus will be
      practically useful for drug repositioning. Supplementary Material is available at
      http://iiis.tsinghua.edu.cn/~compbio/papers/psb2014/psb2014_sm.pdf. 

PMID- 24297543
TI  - Prediction of off-target drug effects through data fusion.
AB  - We present a probabilistic data fusion framework that combines multiple
      computational approaches for drawing relationships between drugs and targets. The
      approach has special relevance to identifying surprising unintended biological
      targets of drugs. Comparisons between molecules are made based on 2D topological
      structural considerations, based on 3D surface characteristics, and based on
      English descriptions of clinical effects. Similarity computations within each
      modality were transformed into probability scores. Given a new molecule along
      with a set of molecules sharing some biological effect, a single score based on
      comparison to the known set is produced, reflecting either 2D similarity, 3D
      similarity, clinical effects similarity or their combination. The methods were
      validated within acurated structural pharmacology database (SPDB) and further
      tested by blind application to data derived from the ChEMBL database. For
      prediction of off-target effects, 3D-similarity performed best as a single
      modality, but combining all methods produced performance gains. Striking examples
      of structurally surprising off-target predictions are presented. 

PMID- 24297544
TI  - Exploring the pharmacogenomics knowledge base (PharmGKB) for repositioning breast
      cancer drugs by leveraging Web ontology language (OWL) and cheminformatics
      approaches.
AB  - Computational drug repositioning leverages computational technology and high
      volume of biomedical data to identify new indications for existing drugs. Since
      it does not require costly experiments that have a high risk of failure, it has
      attracted increasing interest from diverse fields such as biomedical,
      pharmaceutical, and informatics areas. In this study, we used pharmacogenomics
      data generated from pharmacogenomics studies, applied informatics and Semantic
      Web technologies to address the drug repositioning problem. Specifically, we
      explored PharmGKB to identify pharmacogenomics related associations as
      pharmacogenomics profiles for US Food and Drug Administration (FDA) approved
      breast cancer drugs. We then converted and represented these profiles in Semantic
      Web notations, which support automated semantic inference. We successfully
      evaluated the performance and efficacy of the breast cancer drug pharmacogenomics
      profiles by case studies. Our results demonstrate that combination of
      pharmacogenomics data and Semantic Web technology/Cheminformatics approaches
      yields better performance of new indication and possible adverse effects
      prediction for breast cancer drugs. 

PMID- 24297546
TI  - Using the bipartite human phenotype network to reveal pleiotropy and epistasis
      beyond the gene.
AB  - With the rapid increase in the quality and quantity of data generated by modern
      high-throughput sequencing techniques, there has been a need for innovative
      methods able to convert this tremendous amount of data into more accessible
      forms. Networks have been a corner stone of this movement, as they are an
      intuitive way of representing interaction data, yet they offer a full set of
      sophisticated statistical tools to analyze the phenomena they model. We propose a
      novel approach to reveal and analyze pleiotropic and epistatic effects at the
      genome-wide scale using a bipartite network composed of human diseases,
      phenotypic traits, and several types of predictive elements (i.e. SNPs, genes, or
      pathways). We take advantage of publicly available GWAS data, gene and pathway
      databases, and more to construct networks different levels of granularity, from
      common genetic variants to entire biological pathways. We use the connections
      between the layers of the network to approximate the pleiotropy and epistasis
      effects taking place between the traits and the predictive elements. The global
      graph-theory based quantitative methods reveal that the levels of pleiotropy and
      epistasis are comparable for all types of predictive element. The results of the
      magnified "glaucoma" region of the network demonstrate the existence of well
      documented interactions, supported by overlapping genes and biological pathway,
      and more obscure associations. As the amount and complexity of genetic data
      increases, bipartite, and more generally multipartite networks that combine human
      diseases and other physical attributes with layers of genetic information, have
      the potential to become ubiquitous tools in the study of complex genetic and
      phenotypic interactions. 

PMID- 24297548
TI  - Dissection of complex gene expression using the combined analysis of pleiotropy
      and epistasis.
AB  - Global transcript expression experiments are commonly used to investigate the
      biological processes that underlie complex traits. These studies can exhibit
      complex patterns of pleiotropy when trans-acting genetic factors influence
      overlapping sets of multiple transcripts. Dissecting these patterns into
      biological modules with distinct genetic etiology can provide models of how
      genetic variants affect specific processes that contribute to a trait. Here we
      identify transcript modules associated with pleiotropic genetic factors and apply
      genetic interaction analysis to disentangle the regulatory architecture in a
      mouse intercross study of kidney function. The method, called the combined
      analysis of pleiotropy and epistasis (CAPE), has been previously used to model
      genetic networks for multiple physiological traits. It simultaneously models
      multiple phenotypes to identify direct genetic influences as well as influences
      mediated through genetic interactions. We first identify candidate trans
      expression quantitative trait loci (eQTL) and the transcripts potentially
      affected. We then clustered the transcripts into modules of co-expressed genes,
      from which we compute summary module phenotypes. Finally, we applied CAPE to map
      the network of interacting module QTL (modQTL) affecting the gene modules. The
      resulting network mapped how multiple modQTL both directly and indirectly affect
      modules associated with metabolic functions and biosynthetic processes. This work
      demonstrates how the integration of pleiotropic signals in gene expression data
      can be used to infer a complex hypothesis of how multiple loci interact to co
      regulate transcription programs, thereby providing additional constraints to
      prioritize validation experiments. 

PMID- 24297547
TI  - Environment-wide association study (EWAS) for type 2 diabetes in the Marshfield
      Personalized Medicine Research Project Biobank.
AB  - Environment-wide association studies (EWAS) provide a way to uncover the
      environmental mechanisms involved in complex traits in a high-throughput manner.
      Genome-wide association studies have led to the discovery of genetic variants
      associated with many common diseases but do not take into account the
      environmental component of complex phenotypes. This EWAS assesses the
      comprehensive association between environmental variables and the outcome of type
      2 diabetes (T2D) in the Marshfield Personalized Medicine Research Project Biobank
      (Marshfield PMRP). We sought replication in two National Health and Nutrition
      Examination Surveys (NHANES). The Marshfield PMRP currently uses four tools for
      measuring environmental exposures and outcome traits: 1) the PhenX Toolkit
      includes standardized exposure and phenotypic measures across several domains, 2)
      the Diet History Questionnaire (DHQ) is a food frequency questionnaire, 3) the
      Measurement of a Person's Habitual Physical Activity scores the level of an
      individual's physical activity, and 4) electronic health records (EHR) employs
      validated algorithms to establish T2D case-control status. Using PLATO software,
      314 environmental variables were tested for association with T2D using logistic
      regression, adjusting for sex, age, and BMI in over 2,200 European Americans.
      When available, similar variables were tested with the same methods and
      adjustment in samples from NHANES III and NHANES 1999-2002. Twelve and 31
      associations were identified in the Marshfield samples at p<0.01 and p<0.05,
      respectively. Seven and 13 measures replicated in at least one of the NHANES at
      p<0.01 and p<0.05, respectively, with the same direction of effect. The most
      significant environmental exposures associated with T2D status included decreased
      alcohol use as well as increased smoking exposure in childhood and adulthood. The
      results demonstrate the utility of the EWAS method and survey tools for
      identifying environmental components of complex diseases like type 2 diabetes.
      These high-throughput and comprehensive investigation methods can easily be
      applied to investigate the relation between environmental exposures and multiple
      phenotypes in future analyses. 

PMID- 24297549
TI  - Personalized medicine: from genotypes and molecular phenotypes towards therapy-
      session introduction.

PMID- 24297550
TI  - PATH-SCAN: a reporting tool for identifying clinically actionable variants.
AB  - The American College of Medical Genetics and Genomics (ACMG) recently released
      guidelines regarding the reporting of incidental findings in sequencing data.
      Given the availability of Direct to Consumer (DTC) genetic testing and the
      falling cost of whole exome and genome sequencing, individuals will increasingly
      have the opportunity to analyze their own genomic data. We have developed a web
      based tool, PATH-SCAN, which annotates individual genomes and exomes for ClinVar
      designated pathogenic variants found within the genes from the ACMG guidelines.
      Because mutations in these genes predispose individuals to conditions with
      actionable outcomes, our tool will allow individuals or researchers to identify
      potential risk variants in order to consult physicians or genetic counselors for
      further evaluation. Moreover, our tool allows individuals to anonymously submit
      their pathogenic burden, so that we can crowd source the collection of
      quantitative information regarding the frequency of these variants. We tested our
      tool on 1092 publicly available genomes from the 1000 Genomes project, 163
      genomes from the Personal Genome Project, and 15 genomes from a clinical genome
      sequencing research project. Excluding the most commonly seen variant in 1000
      Genomes, about 20% of all genomes analyzed had a ClinVar designated pathogenic
      variant that required further evaluation. 

PMID- 24297551
TI  - Imputation-based assessment of next generation rare exome variant arrays.
AB  - A striking finding from recent large-scale sequencing efforts is that the vast
      majority of variants in the human genome are rare and found within single
      populations or lineages. These observations hold important implications for the
      design of the next round of disease variant discovery efforts-if genetic variants
      that influence disease risk follow the same trend, then we expect to see
      population-specific disease associations that require large sample sizes for
      detection. To address this challenge, and due to the still prohibitive cost of
      sequencing large cohorts, researchers have developed a new generation of low-cost
      genotyping arrays that assay rare variation previously identified from large
      exome sequencing studies. Genotyping approaches rely not only on directly
      observing variants, but also on phasing and imputation methods that use publicly
      available reference panels to infer unobserved variants in a study cohort. Rare
      variant exome arrays are intentionally enriched for variants likely to be disease
      causing, and here we assay the ability of the first commercially available rare
      exome variant array (the Illumina Infinium HumanExome BeadChip) to also tag other
      potentially damaging variants not molecularly assayed. Using full sequence data
      from chromosome 22 from the phase I 1000 Genomes Project, we evaluate three
      methods for imputation (BEAGLE, MaCH-Admix, and SHAPEIT2/IMPUTE2) with the rare
      exome variant array under varied study panel sizes, reference panel sizes, and LD
      structures via population differences. We find that imputation is more accurate
      across both the genome and exome for common variant arrays than the next
      generation array for all allele frequencies, including rare alleles. We also find
      that imputation is the least accurate in African populations, and accuracy is
      substantially improved for rare variants when the same population is included in
      the reference panel. Depending on the goals of GWAS researchers, our results will
      aid budget decisions by helping determine whether money is best spent sequencing
      the genomes of smaller sample sizes, genotyping larger sample sizes with rare
      and/or common variant arrays and imputing SNPs, or some combination of the two. 

PMID- 24297553
TI  - Robust reverse engineering of dynamic gene networks under sample size
      heterogeneity.
AB  - Simultaneously reverse engineering a collection of condition-specific gene
      networks from gene expression microarray data to uncover dynamic mechanisms is a
      key challenge in systems biology. However, existing methods for this task are
      very sensitive to variations in the size of the microarray samples across
      different biological conditions (which we term sample size heterogeneity in
      network reconstruction), and can potentially produce misleading results that can
      lead to incorrect biological interpretation. In this work, we develop a more
      robust framework that addresses this novel problem. Just like microarray
      measurements across conditions must undergo proper normalization on their
      magnitudes before entering subsequent analysis, we argue that networks across
      conditions also need to be "normalized" on their density when they are
      constructed, and we provide an algorithm that allows such normalization to be
      facilitated while estimating the networks. We show the quantitative advantages of
      our approach on synthetic and real data. Our analysis of a hematopoietic stem
      cell dataset reveals interesting results, some of which are confirmed by
      previously validated results. 

PMID- 24297552
TI  - Utilization of an EMR-biorepository to identify the genetic predictors of
      calcineurin-inhibitor toxicity in heart transplant recipients.
AB  - Calcineurin-inhibitors CI are immunosuppressive agents prescribed to patients
      after solid organ transplant to prevent rejection. Although these drugs have been
      transformative for allograft survival, long-term use is complicated by side
      effects including nephrotoxicity. Given the narrow therapeutic index of CI,
      therapeutic drug monitoring is used to prevent acute rejection from underdosing
      and acute toxicity from overdosing, but drug monitoring does not alleviate long
      term side effects. Patients on calcineurin-inhibitors for long periods almost
      universally experience declines in renal function, and a subpopulation of
      transplant recipients ultimately develop chronic kidney disease that may progress
      to end stage renal disease attributable to calcineurin inhibitor toxicity (CNIT).
      Pharmacogenomics has the potential to identify patients who are at high risk for
      developing advanced chronic kidney disease caused by CNIT and providing them with
      existing alternate immunosuppressive therapy. In this study we utilized BioVU,
      Vanderbilt University Medical Center's DNA biorepository linked to de-identified
      electronic medical records to identify a cohort of 115 heart transplant
      recipients prescribed calcineurin-inhibitors to identify genetic risk factors for
      CNIT We identified 37 cases of nephrotoxicity in our cohort, defining
      nephrotoxicity as a monthly median estimated glomerular filtration rate (eGFR)<30
      mL/min/1.73 m2 at least six months post-transplant for at least three consecutive
      months. All heart transplant patients were genotyped on the Illumina ADME Core
      Panel, a pharmacogenomic genotyping platform that assays 184 variants across 34
      genes. In Cox regression analysis adjusting for age at transplant, pre-transplant
      chronic kidney disease, pre-transplant diabetes, and the three most significant
      principal components (PCAs), we did not identify any markers that met our
      multiple-testing threshold. As a secondary analysis we also modeled post
      transplant eGFR directly with linear mixed models adjusted for age at transplant,
      cyclosporine use, median BMI, and the three most significant principal
      components. While no SNPs met our threshold for significance, a SNP previously
      identified in genetic studies of the dosing of tacrolimus CYP34A rs776746,
      replicated in an adjusted analysis at an uncorrected p-value of 0.02
      (coeff(S.E.)=14.60(6.41)). While larger independent studies will be required to
      further validate this finding, this study underscores the EMRs usefulness as a
      resource for longitudinal pharmacogenetic study designs.

PMID- 24297554
TI  - Variant priorization and analysis incorporating problematic regions of the
      genome.
AB  - In case-control studies of rare Mendelian disorders and complex diseases, the
      power to detect variant and gene-level associations of a given effect size is
      limited by the size of the study sample. Paradoxically, low statistical power may
      increase the likelihood that a statistically significant finding is also a false
      positive. The prioritization of variants based on call quality, putative effects
      on protein function, the predicted degree of deleteriousness, and allele
      frequency is often used as a mechanism for reducing the occurrence of false
      positives, while preserving the set of variants most likely to contain true
      disease associations. We propose that specificity can be further improved by
      considering errors that are specific to the regions of the genome being
      sequenced. These problematic regions (PRs) are identified a-priori and are used
      to down-weight constitutive variants in a case-control analysis. Using samples
      drawn from 1000-Genomes, we illustrate the utility of PRs in identifying true
      variant and gene associations using a case-control study on a known Mendelian
      disease, cystic fibrosis (CF).

PMID- 24297555
TI  - Bags of words models of epitope sets: HIV viral load regression with counting
      grids.
AB  - The immune system gathers evidence of the execution of various molecular
      processes, both foreign and the cells' own, as time- and space-varying sets of
      epitopes, small linear or conformational segments of the proteins involved in
      these processes. Epitopes do not have any obvious ordering in this scheme: The
      immune system simply sees these epitope sets as disordered "bags" of simple
      signatures based on whose contents the actions need to be decided. The immense
      landscape of possible bags of epitopes is shaped by the cellular pathways in
      various cells, as well as the characteristics of the internal sampling process
      that chooses and brings epitopes to cellular surface. As a consequence, upon the
      infection by the same pathogen, different individuals' cells present very
      different epitope sets. Modeling this landscape should thus be a key step in
      computational immunology. We show that among possible bag-of-words models, the
      counting grid is most fit for modeling cellular presentation. We describe each
      patient by a bag-of-peptides they are likely to present on the cellular surface.
      In regression tests, we found that compared to the state-of-the-art, counting
      grids explain more than twice as much of the log viral load variance in these
      patients. This is potentially a significant advancement in the field, given that
      a large part of the log viral load variance also depends on the infecting HIV
      strain, and that HIV polymorphisms themselves are known to strongly associate
      with HLA types, both effects beyond what is modeled here. 

PMID- 24297556
TI  - Joint association discovery and diagnosis of Alzheimer's disease by supervised
      heterogeneous multiview learning.
AB  - A key step for Alzheimer's disease (AD) study is to identify associations between
      genetic variations and intermediate phenotypes (e.g., brain structures). At the
      same time, it is crucial to develop a noninvasive means for AD diagnosis.
      Although these two tasks-association discovery and disease diagnosis-have been
      treated separately by a variety of approaches, they are tightly coupled due to
      their common biological basis. We hypothesize that the two tasks can potentially
      benefit each other by a joint analysis, because (i) the association study
      discovers correlated biomarkers from different data sources, which may help
      improve diagnosis accuracy, and (ii) the disease status may help identify disease
      sensitive associations between genetic variations and MRI features. Based on this
      hypothesis, we present a new sparse Bayesian approach for joint association study
      and disease diagnosis. In this approach, common latent features are extracted
      from different data sources based on sparse projection matrices and used to
      predict multiple disease severity levels based on Gaussian process ordinal
      regression; in return, the disease status is used to guide the discovery of
      relationships between the data sources. The sparse projection matrices not only
      reveal the associations but also select groups of biomarkers related to AD. To
      learn the model from data, we develop an efficient variational expectation
      maximization algorithm. Simulation results demonstrate that our approach achieves
      higher accuracy in both predicting ordinal labels and discovering associations
      between data sources than alternative methods. We apply our approach to an
      imaging genetics dataset of AD. Our joint analysis approach not only identifies
      meaningful and interesting associations between genetic variations, brain
      structures, and AD status, but also achieves significantly higher accuracy for
      predicting ordinal AD stages than the competing methods. 

PMID- 24297558
TI  - Vector quantization kernels for the classification of protein sequences and
      structures.
AB  - We propose a new kernel-based method for the classification of protein sequences
      and structures. We first represent each protein as a set of time series data
      using several structural, physicochemical, and predicted properties such as a
      sequence of consecutive dihedral angles, hydrophobicity indices, or predictions
      of disordered regions. A kernel function is then computed for pairs of proteins,
      exploiting the principles of vector quantization and subsequently used with
      support vector machines for protein classification. Although our method requires
      a significant pre-processing step, it is fast in the training and prediction
      stages owing to the linear complexity of kernel computation with the length of
      protein sequences. We evaluate our approach on two protein classification tasks
      involving the prediction of SCOP structural classes and catalytic activity
      according to the Gene Ontology. We provide evidence that the method is
      competitive when compared to string kernels, and useful for a range of protein
      classification tasks. Furthermore, the applicability of our approach extends
      beyond computational biology to any classification of time series data. 

PMID- 24297559
TI  - Combining heterogenous data for prediction of disease related and pharmacogenes.
AB  - Identifying genetic variants that affect drug response or play a role in disease
      is an important task for clinicians and researchers. Before individual variants
      can be explored efficiently for effect on drug response or disease relationships,
      specific candidate genes must be identified. While many methods rank candidate
      genes through the use of sequence features and network topology, only a few
      exploit the information contained in the biomedical literature. In this work, we
      train and test a classifier on known pharmacogenes from PharmGKB and present a
      classifier that predicts pharmacogenes on a genome-wide scale using only Gene
      Ontology annotations and simple features mined from the biomedical literature.
      Performance of F=0.86, AUC=0.860 is achieved. The top 10 predicted genes are
      analyzed. Additionally, a set of enriched pharmacogenic Gene Ontology concepts is
      produced. 

PMID- 24297560
TI  - A novel profile biomarker diagnosis for mass spectral proteomics.
AB  - Mass spectrometry based proteomics technologies have allowed for a great progress
      in identifying disease biomarkers for clinical diagnosis and prognosis. However,
      they face acute challenges from a data reproducibility standpoint, in that no two
      independent studies have been found to produce the same proteomic patterns. Such
      reproducibility issues cause the identified biomarker patterns to lose
      repeatability and prevent real clinical usage. In this work, we propose a profile
      biomarker approach to overcome this problem from a machine-learning viewpoint by
      developing a novel derivative component analysis (DCA). As an implicit feature
      selection algorithm, derivative component analysis enables the separation of true
      signals from red herrings by capturing subtle data behaviors and removing system
      noises from a proteomic profile. We further demonstrate its advantages in disease
      diagnosis by viewing input data as a profile biomarker. The results from our
      profile biomarker diagnosis suggest an effective solution to overcoming
      proteomics data's reproducibility problem, present an alternative method for
      biomarker discovery in proteomics, and provide a good candidate for clinical
      proteomic diagnosis. 

PMID- 24297561
TI  - Towards pathway curation through literature mining--a case study using PharmGKB.
AB  - The creation of biological pathway knowledge bases is largely driven by manual
      effort to curate based on evidences from the scientific literature. It is highly
      challenging for the curators to keep up with the literature. Text mining
      applications have been developed in the last decade to assist human curators to
      speed up the curation pace where majority of them aim to identify the most
      relevant papers for curation with little attempt to directly extract the pathway
      information from text. In this paper, we describe a rule-based literature mining
      system to extract pathway information from text. We evaluated the system using
      curated pharmacokinetic (PK) and pharmacodynamic (PD) pathways in PharmGKB. The
      system achieved an F-measure of 63.11% and 34.99% for entity extraction and event
      extraction respectively against all PubMed abstracts cited in PharmGKB. It may be
      possible to improve the system performance by incorporating using statistical
      machine learning approaches. This study also helped us gain insights into the
      barriers towards automated event extraction from text for pathway curation. 

PMID- 24297562
TI  - Sparse generalized functional linear model for predicting remission status of
      depression patients.
AB  - Complex diseases such as major depression affect people over time in complicated
      patterns. Longitudinal data analysis is thus crucial for understanding and
      prognosis of such diseases and has received considerable attention in the
      biomedical research community. Traditional classification and regression methods
      have been commonly applied in a simple (controlled) clinical setting with a small
      number of time points. However, these methods cannot be easily extended to the
      more general setting for longitudinal analysis, as they are not inherently built
      for time-dependent data. Functional regression, in contrast, is capable of
      identifying the relationship between features and outcomes along with time
      information by assuming features and/or outcomes as random functions over time
      rather than independent random variables. In this paper, we propose a novel
      sparse generalized functional linear model for the prediction of treatment
      remission status of the depression participants with longitudinal features.
      Compared to traditional functional regression models, our model enables high
      dimensional learning, smoothness of functional coefficients, longitudinal feature
      selection and interpretable estimation of functional coefficients. Extensive
      experiments have been conducted on the Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) data set and the results show that the proposed
      sparse functional regression method achieves significantly higher prediction
      power than existing approaches. 

PMID- 24297563
TI  - Development of a data-mining algorithm to identify ages at reproductive
      milestones in electronic medical records.
AB  - Electronic medical records (EMRs) are becoming more widely implemented following
      directives from the federal government and incentives for supplemental
      reimbursements for Medicare and Medicaid claims. Replete with rich phenotypic
      data, EMRs offer a unique opportunity for clinicians and researchers to identify
      potential research cohorts and perform epidemiologic studies. Notable limitations
      to the traditional epidemiologic study include cost, time to complete the study,
      and limited ancestral diversity; EMR-based epidemiologic studies offer an
      alternative. The Epidemiologic Architecture for Genes Linked to Environment
      (EAGLE) Study, as part of the Population Architecture using Genomics and
      Epidemiology (PAGE) I Study, has genotyped more than 15,000 patients of diverse
      ancestry in BioVU, the Vanderbilt University Medical Center's biorepository
      linked to the EMR (EAGLE BioVU). We report here the development and performance
      of data-mining techniques used to identify the age at menarche (AM) and age at
      menopause (AAM), important milestones in the reproductive lifespan, in women from
      EAGLE BioVU for genetic association studies. In addition, we demonstrate the
      ability to discriminate age at naturally-occurring menopause (ANM) from medically
      induced menopause. Unusual timing of these events may indicate underlying
      pathologies and increased risk for some complex diseases and cancer; however,
      they are not consistently recorded in the EMR. Our algorithm offers a mechanism
      by which to extract these data for clinical and research goals. 

PMID- 24297564
TI  - An efficient algorithm to integrate network and attribute data for gene function
      prediction.
AB  - Label propagation methods are extremely well-suited for a variety of biomedical
      prediction tasks based on network data. However, these algorithms cannot be used
      to integrate feature-based data sources with networks. We propose an efficient
      learning algorithm to integrate these two types of heterogeneous data sources to
      perform binary prediction tasks on node features (e.g., gene prioritization,
      disease gene prediction). Our method, LMGraph, consists of two steps. In the
      first step, we extract a small set of "network features" from the nodes of
      networks that represent connectivity with labeled nodes in the prediction tasks.
      In the second step, we apply a simple weighting scheme in conjunction with linear
      classifiers to combine these network features with other feature data. This two
      step procedure allows us to (i) learn highly scalable and computationally
      efficient linear classifiers, (ii) and seamlessly combine feature-based data
      sources with networks. Our method is much faster than label propagation which is
      already known to be computationally efficient on large-scale prediction problems.
      Experiments on multiple functional interaction networks from three species
      (mouse, y, C.elegans) with tens of thousands of nodes and hundreds of binary
      prediction tasks demonstrate the efficacy of our method. 

PMID- 24297565
TI  - Matrix factorization-based data fusion for gene function prediction in baker's
      yeast and slime mold.
AB  - The development of effective methods for the characterization of gene functions
      that are able to combine diverse data sources in a sound and easily-extendible
      way is an important goal in computational biology. We have previously developed a
      general matrix factorization-based data fusion approach for gene function
      prediction. In this manuscript, we show that this data fusion approach can be
      applied to gene function prediction and that it can fuse various heterogeneous
      data sources, such as gene expression profiles, known protein annotations,
      interaction and literature data. The fusion is achieved by simultaneous matrix
      tri-factorization that shares matrix factors between sources. We demonstrate the
      effectiveness of the approach by evaluating its performance on predicting
      ontological annotations in slime mold D. discoideum and on recognizing proteins
      of baker's yeast S. cerevisiae that participate in the ribosome or are located in
      the cell membrane. Our approach achieves predictive performance comparable to
      that of the state-of-the-art kernel-based data fusion, but requires fewer data
      preprocessing steps. 

PMID- 24297566
TI  - Applications of bioinformatics to non-coding RNAs in the era of next-generation
      sequencing.
AB  - The human genome encodes a large number of non-coding RNAs, which employ a new
      and crucial layer of biological regulation in addition to proteins. Technical
      advancement in recent years, particularly, the wide application of next
      generation sequencing analysis, provide an unprecedented opportunity to identify
      new non-coding RNAs and investigate their functions and regulatory mechanisms.
      The aim of this workshop is to bring together experimental and computational
      biologist to exchange ideas on non-coding RNA studies. 

PMID- 24297567
TI  - Building the next generation of quantitative biologists.
AB  - Many colleges and universities across the globe now offer bachelors, masters, and
      doctoral degrees, along with certificate programs in bioinformatics. While there
      is some consensus surrounding curricula competencies, programs vary greatly in
      their core foci, with some leaning heavily toward the biological sciences and
      others toward quantitative areas. This allows prospective students to choose a
      program that best fits their interests and career goals. In the digital age, most
      scientific fields are facing an enormous growth of data, and as a consequence,
      the goals and challenges of bioinformatics are rapidly changing; this requires
      that bioinformatics education also change. In this workshop, we seek to ascertain
      current trends in bioinformatics education by asking the question, "What are the
      core competencies all bioinformaticians should have at the end of their training,
      and how successful have programs been in placing students in desired careers?" 

PMID- 24297568
TI  - Uncovering the etiology of autism spectrum disorders: genomics, bioinformatics,
      environment, data collection and exploration, and future possibilities.
AB  - A clear and predictive understanding of the etiology of autism spectrum disorders
      (ASD), a group of neurodevelopmental disorders characterized by varying deficits
      in social interaction and communication as well as repetitive behaviors, has not
      yet been achieved. There remains active debate about the origins of autism, and
      the degree to which genetic and environmental factors, and their interplay,
      produce the range and heterogeneity of cognitive, developmental, and behavioral
      features seen in children carrying a diagnosis of ASD. Unlocking the causes of
      these complex developmental disorders will require a collaboration of experts in
      many disciplines, including clinicians, environmental exposure experts,
      bioinformaticists, geneticists, and computer scientists. For this workshop we
      invited prominent researchers in the field of autism, covering a range of topics
      from genetic and environmental research to ethical considerations. The goal of
      this workshop: provide an introduction to the current state of autism research,
      highlighting the potential for multi-disciplinary collaborations that rigorously
      evaluate the many potential contributors to ASD. It is further anticipated that
      approaches that successfully advance the understanding of ASD can be applied to
      the study of other common, complex disorders. Herein we provide a short review of
      ASD and the work of the invited speakers. 

PMID- 24297569
TI  - Programmed death ligand-1 over-expression correlates with malignancy and
      contributes to immune regulation in ovarian cancer.
AB  - The programmed death-1 (PD-1) pathway is important in the maintenance of
      peripheral tolerance and homeostasis through suppression of T cell receptor
      signaling. As such, it is employed by many tumors as a means of immune escape. We
      have investigated the role of this pathway in human ovarian cancer (OC) to assess
      its potential role as a diagnostic and/or prognostic marker and therapeutic
      target, following recent clinical trial success of antibody therapy directed at
      this pathway. We show programmed death ligand-1 (PD-L1) expression on monocytes
      in the ascites and blood of patients with malignant OC is strikingly higher than
      those with benign/borderline disease, with no overlap in the values between these
      groups. We characterize the regulation of this molecule and show a role of IL-10
      present in ascitic fluid. Flow cytometric analysis of T cells present in the
      ascites and blood showed a correlation of PD-1 expression with malignant tumors
      versus benign/borderline, in a similar manner to PD-L1 expression on monocytes.
      Finally, we demonstrate functional links between PD-L1 expression on monocytes
      and OC tumor cells with suppression of T cell responses. Overall, we present data
      based on samples obtained from women with ovarian cancer, suggesting the PD-1
      pathway may be used as a reliable diagnostic marker in OC, as well as a viable
      target for use with PD-1/PD-L1-directed antibody immunotherapy. 

PMID- 24297570
TI  - Expression of tissue factor signaling pathway elements correlates with the
      production of vascular endothelial growth factor and interleukin-8 in human
      astrocytoma patients.
AB  - The expression levels of tissue factor (TF), the clotting initiator protein, have
      been correlated with angiogenesis and the histological grade of malignancy in
      glioma patients. The pro-tumor function of TF is linked to a family of G protein
      coupled receptors known as protease-activated receptors (PARs), which may be
      activated by blood coagulation proteases. Activation of PARs elicits a number of
      responses, including the expression of vascular endothelial growth factor (VEGF)
      and interleukin-8 (IL-8). In the present study, we analyzed the expression of TF
      signaling pathway elements (TF, PAR1 and PAR2) and evaluated their correlation
      with the expression of downstream products (VEGF and IL-8) in human astrocytoma
      patients. Quantitative PCR (qPCR) showed a significant increase in TF expression
      in grade IV (glioblastoma) tumors, which was inversely correlated with the
      expression of the tumor-suppressor PTEN. Immunohistochemistry and qPCR analyses
      demonstrated a highly significant elevation in the expression of PAR1, but not
      PAR2, in tumor samples from high-grade astrocytoma patients. The elevated VEGF
      expression levels detected in the high-grade astrocytoma samples were positively
      correlated with TF, PAR1 and PAR2 expression. In addition, IL-8 was significantly
      increased in glioblastoma patients and positively correlated with TF and PAR2
      expression. Further in vitro assays employing the human glioma cell lines U87-MG
      and HOG demonstrated that a synthetic peptide PAR2 agonist stimulated VEGF and IL
      8 production. Our findings suggest a role for TF signaling pathway elements in
      astrocytoma progression, particularly in glioblastoma. Therefore, TF/PAR
      signaling elements may be suitable targets for the development of new therapies
      for the treatment of aggressive glioma.

PMID- 24297571
TI  - Turn-off Fluorescence Chemosensor for Iron with Bis(2-aminoethyl)-2-(9
      fluorenyl)malonamide Functionlized SBA-15.
AB  - An bis(2-aminoethyl)-2-(9-fluorenyl)malonamide as fluorophore ligand was
      immobilized onto mesoporous silica type SBA-15 via post synthesis grafting. The
      obtained material was characterized by small and wide angle X-ray diffraction, N2
      adsorption-desorption, Fourier transform infrared spectroscopy, Raman
      spectroscopy and thermogravimetric analysis that indicate the successful
      immobilization of the ligand on the surface of mesoporous silica. The sensing
      ability of the obtained material was studied by addition of the cations Fe(3+),
      Mg(2+), Cr(3+), Co(2+), Ni(2+), Cu(2+), Hg(2+) and Zn(2+) to water suspensions of
      the assayed solid. Of all the cations tested addition of Fe(3+) ion to a
      suspension of this material resulted in the largest decrease in the fluorescence
      intensity. Turn-off photoluminescence of this material was remarkably observed
      for iron ions in comparing of the other cations. A good linearity between the
      fluorescence intensity of this material and the concentration of Fe(3+) ion is
      constructed, which enables it as a fluorescence chemosensor for detecting the
      Fe(3+) ion with a suitable detection limit of 1.35 * 10(-5). It can be introduced
      as a novel fluorescent sensor in aqueous solution for a lot of practical
      applications in chemical, environmental and biological systems. 

PMID- 24297572
TI  - Phosphorus(V)corrole- Porphyrin Based Hetero Trimers: Synthesis, Spectroscopy and
      Photochemistry.
AB  - 'Axial-bonding'-type hetero trimers have been constructed by employing a simple
      'inorganic' reaction such as axial bond formation of main group element
      containing phosphorus corrole. The approach is simple and modular in nature. The
      architecture of these hetero trimers such that, while a phosphorus(V)corrole
      forms the basal scaffolding unit, either two free-base porphyrins [(H 2 ) 2 
      PCor] or Zn(II) porphyrins [(Zn) 2 -PCor] occupy the two axial sites via an
      aryloxy bridge. Both hetero trimeric species have been completely characterized
      by mass (FAB), UV/Vis, proton nuclear magnetic resonance spectroscopies and also
      by the differential pulse voltammetric method. Comparison of their spectroscopic
      and electrochemical data of these trimers with those of the corresponding
      reference compounds reveal that there is no apparent ring-to-ring interactions in
      these 'vertically' linked hetero trimers. Reduced fluorescence quantum yields
      were observed for [(H 2 ) 2 -PCor] and [(Zn) 2 -PCor] when compared to
      corresponding monomeric chromophores. Finally, a comparison is made between the
      presently reported phosphorus(V)corrole based hetero arrays and the previously
      reported analogous arrays based on Ge(IV)corrole with regard to their
      spectroscopic properties and photochemical activities. 

PMID- 24297573
TI  - Synthesis, CMC Determination, Antimicrobial Activity and Nucleic Acid Binding of
      A Surfactant Copper(II) Complex Containing Phenanthroline and Alanine Schiff
      Base.
AB  - A new water-soluble surfactant copper(II) complex [Cu(sal-ala)(phen)(DA)] (sal
      ala = salicylalanine, phen = 1,10-phenanthroline, DA = dodecylamine), has been
      synthesized and characterized by physico-chemical and spectroscopic methods. The
      critical micelle concentration (CMC) values of this surfactant-copper(II) complex
      in aqueous solution were obtained from conductance measurements. Specific
      conductivity data (at 303, 308, 313. 318 and 323 K) served for the evaluation of
      the temperature-dependent CMC and the thermodynamics of micellization
      (DeltaG(0)m, DeltaH(0)m and DeltaS(0)m). The interaction of this complex with
      nucleic acids (DNA and RNA) has been explored by using electronic absorption
      spectral titration, competitive binding experiment, cyclic voltammetry, circular
      dichroism (CD) spectra, and viscosity measurements. Electronic absorption studies
      have revealed that the complex can bind to nucleic acids by the intercalative
      binding mode which has been verified by viscosity measurements. The DNA binding
      constants have also been calculated (Kb = 1.2 * 10(5) M(-1) for DNA and Kb = 1.6
      * 10(5) M(-1) for RNA). Competitive binding study with ethidium bromide (EB)
      showed that the complex exhibits the ability to displace the DNA-bound-EB
      indicating that the complex binds to DNA in strong competition with EB for the
      intercalative binding site. The presence of hydrophobic ligands, alanine Schiff
      base, phenanthroline and long aliphatic chain amine in the complex were
      responsible for this strong intercalative binding. The surfactant-copper (II)
      complex was screened for its antibacterial and antifungal activities against
      various microorganisms. The results were compared with the standard drugs,
      amikacin(antibacterial) and ketokonazole(antifungal). 

PMID- 24297574
TI  - Positive outcome following early diagnosis and treatment of pyridoxal-5'
      phosphate oxidase deficiency: a case report.
AB  - Pyridoxal-5'-phosphate oxidase (PNPO) deficiency is a rare autosomal recessive,
      vitamin-responsive metabolic disorder causing refractory neonatal seizures that
      respond to the administration of pyridoxal-5'-phosphate (PLP). There are
      currently few case studies that have documented the functional outcome in PNPO
      deficiency, which remains poor in the majority of cases. We present the case of a
      male infant born at 35 weeks gestation who promptly responded to oral
      administration of PLP, following resistance to common anticonvulsive therapy and
      to a pyridoxine trial. Neurological outcome at 21 months is favorable and
      illustrates the importance of standardized vitamin trials in the acute setting of
      "therapy-resistant" neonatal seizures. Early recognition of PNPO deficiency and
      appropriate intervention might be associated with a more favorable outcome than
      initially considered. 

PMID- 24297575
TI  - Magnetic resonance imaging (MRI) artefacts in hip prostheses: a comparison of
      different prosthetic compositions.
AB  - PURPOSE: The purpose of the study was to compare the artefacts produced by
      different hip prostheses on magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: An identical MRI protocol was used to perform a quali-quantitative in
      vitro evaluation of artefacts caused by different hip prosthetic materials at
      different field strengths: prosthesis number 1, composed of cobalt-chrome
      molybdenum (head and stem); prosthesis number 2, composed of ceramic (head) and
      titanium (stem); prosthesis number 3, composed of cobalt-chrome (head) and
      titanium (stem). All prostheses were imaged with both a clinical 1 Tesla (T)
      (Signa Horizon, General Electrics) and 1.5 T (Achieva, Philips) MRI system, using
      spin echo (SE) and gradient echo (GRE) sequences: sagittal T1 SE, coronal T2 fast
      SE (FSE), axial T1 SE, axial T2 FSE, sagittal T2 GRE, axial T2* GRE, coronal T1
      GRE, axial T1 GRE. The artefacts produced by each prosthesis were assessed in
      each sequence at the different field strengths, by measuring the two longest
      diameters of the artefact in each section and sequence and comparing them to the
      actual diameters so as to obtain a ratio expressing the effective degree of
      artefact. RESULTS: Cobalt-chrome produced the largest artefacts both in SE (1.73
      at 1 T and 2.37 at 1.5 T) and GRE sequences (2.8 at 1 T and 3.06 at 1.5 T)
      followed by titanium (SE, 1.6 at 1 T, 2.13 at 1.5 T; GRE, 2 at 1 T, 2.94 at 1.5
      T) and cobalt-chrome-molybdenum (SE, 1.51 at 1 T, 1.67 at 1.5 T; GRE, 2.13 at 1 T
      and 2.48 at 1.5 T); ceramic produced the smallest artefacts in all sequences (SE,
      1.0 at 1 T and 1.18 at 1.5 T; GRE, 1.3 at 1 T and 1.22 at 1.5T). Increasing the
      magnetic field strength, titanium showed the greatest variations in artefact
      size, and ceramic the smallest ones. CONCLUSIONS: The composition of prosthetic
      implants is decisive in determining the quality of MR imaging.

PMID- 24297576
TI  - Saber-sheath trachea as a marker of severe airflow obstruction in chronic
      obstructive pulmonary disease.
AB  - PURPOSE: Saber-sheath trachea is a specific radiographic parameter for chronic
      obstructive pulmonary disease (COPD), which consists of marked coronal narrowing
      associated with sagittal widening (tracheal index <2/3-0.67). The aim of this
      study was to investigate the correlation between saber-sheath trachea and
      clinical-radiological findings in a group of patients with COPD of varying
      severity. MATERIALS AND METHODS: We evaluated the chest radiographs of 71
      patients with COPD distributed as follows: GOLD class I, 8/71 (11.3 %); class II,
      34/71 (47.9 %); class III, 16/71(22.5 %); class IV, 13/71 (18.3 %). In 52/71
      (73.2 %) patients we also evaluated chest computed tomography (CT) scans. We
      analyzed the prevalence of saber-sheath trachea and its correlation with the
      Tiffenau index, GOLD stage and radiological signs of COPD. Moreover, we evaluated
      the sensitivity, specificity and accuracy of chest radiography as compared to CT
      taken as the gold standard, and the correlation between the radiographic and CT
      tracheal index. RESULTS: Saber-sheath trachea was found in 18/71 (25.4 %)
      patients, with a greater prevalence in patients with lower Tiffenau Index (p =
      0.02), GOLD stages III-IV and visual severity score 3 (severe) on chest CT. Saber
      sheath trachea was not found to be related to other radiological signs of COPD.
      The sensitivity, specificity and accuracy values of radiography were 72.2, 97.0
      and 88.5 %, with perfect concordance between the radiographic and CT tracheal
      index (p < 0.00001). CONCLUSION: Saber-sheath trachea is linked to the functional
      severity of airway obstruction, but not to other radiological signs of COPD.
      Thus, evaluation of the trachea at chest radiography is strongly recommended.

PMID- 24297577
TI  - Endovascular treatment of spontaneous extraperitoneal haemorrhage: immediate and
      long-term clinical efficiency.
AB  - PURPOSE: This study aimed to evaluate the effectiveness of transcatheter
      embolisation in the treatment of spontaneous extraperitoneal haemorrhage (SEH).
      MATERIALS AND METHODS: We retrospectively evaluated the technical and clinical
      success in terms of immediate and long-term mortality in a series of patients who
      underwent endovascular treatment of SEH from January 2005 to December 2010. A
      statistical comparison of pre- and postoperative transfusion requirements was
      performed by using the Student's t test, with statistical significance set at p <
      0.005. RESULTS: In the period considered, 30 patients (16 women and 14 men; mean
      age, 73.3 years +/-15.6) with SEH underwent endovascular treatment. Technical
      success was obtained in all cases (100 %), and a statistically significant
      reduction in blood transfusion requirements was observed (mean preoperative
      requirement: 7.5 U/day +/-3; mean postoperative requirement 2.8 U/day) (p <
      0.005). We observed a postoperative mortality of 10 % (3/30 patients) and
      mortality at 6 and 12 months was 14.8 % (4/27 patients) and 26 % (6/23 patients),
      respectively. CONCLUSION: According to our experience and to the literature,
      transcatheter arterial embolisation represents the treatment of choice in
      patients with SEH, as it ensures complete therapeutic success.

PMID- 24297578
TI  - Ultrasound-guided anterior axilla musculocutaneous nerve block.
AB  - PURPOSE: This paper presents a technique of ultrasound-guided localisation and
      block of the musculocutaneous nerve through the anterior wall of the axilla.
      MATERIALS AND METHODS: Twenty patients (7 males and 13 females; mean age, 35
      years) had axillary nerve block for upper extremity trauma. With the arm
      adducted, the ultrasound probe was positioned on the anterior axillary wall; the
      axillary artery, coracobrachialis and pectoralis major muscles and lateral cord
      of brachial plexus were visualised in cross section. With continuous imaging of
      the axillary artery in cross section, the ultrasound probe was slowly moved
      towards the biceps muscle until the musculocutaneous nerve appeared crossing the
      coracobrachialis muscle. After ultrasound localisation of the musculocutaneous
      nerve, the arm was abducted and externally rotated, and the nerve was identified
      with nerve stimulation and blocked. The quality of sensory and motor nerve block,
      as well as of ultrasound imaging were evaluated. RESULTS: Ultrasound-guided block
      of the musculocutaneous nerve was excellent and complete in 18 of the 20
      patients. In two patients, the musculocutaneous nerve was fused with the median
      nerve and the nerve block was repeated successfully with the same technique. The
      quality of ultrasound imaging was excellent in all patients. No patient
      experienced pain or tourniquet discomfort during surgery, or any other nerve
      block-related complication. CONCLUSION: The anterior axillary ultrasound view
      provides for complete nerve block and imaging of the entire course of the
      musculocutaneous nerve and its relations with adjacent structures with excellent
      quality.

PMID- 24297579
TI  - Outcomes of antiplatelet therapy for haemorrhage patients after thrombolysis: a
      prospective study based on susceptibility-weighted imaging.
AB  - PURPOSE: The authors evaluated the effect of susceptibility-weighted imaging
      (SWI) for antiplatelet therapy on post-thrombolysis microbleeds (MB). MATERIALS
      AND METHODS: A total of 146 patients without symptomatic intracranial haemorrhage
      on computed tomography after thrombolysis were allocated to two groups: group A
      (n = 72) received antiplatelets 24 h after recombinant tissue plasminogen
      activator, regardless of SWI-detected haemorrhage; group B (n = 74) received
      antiplatelets for patients without SWI-visualised haemorrhage. RESULTS:
      Haemorrhage was detected by SWI in 22 and 28 patients in groups A and B,
      respectively. The difference in mean NIHSS (National Institutes of Health Stroke
      Scale) score in group A between baseline and 6, 24 h, 7, 14 days was -1.6, -1.7, 
      3.6, -5.9, respectively; in group B, the difference in mean NIHSS score between
      baseline and 6, 24 h, 7, 14 days was -2.6, -3.3, -5.4, -8.7, respectively. The
      difference between groups in reduction of mean NIHSS score from baseline was 1.0
      (p < 0.001) at 6 h, 1.6 (p < 0.001) at 24 h, 1.8 (p = 0.001) at 7 days and 2.8 (p
      < 0.001) at 14 days. NIHSS scores at 7, 14 days and modified Rankin scale at 90
      days were significantly lower in haemorrhage patients in groups B than in A,
      whereas the hospital stay was shorter and the rate of favourable outcome at 90
      days was higher. CONCLUSION: Our results indicated that SWI was an effective
      approach for the guidance of antiplatelet therapy in post-thrombolysis MB.

PMID- 24297580
TI  - Work stress and metabolic syndrome in radiologists: first evidence.
AB  - PURPOSE: Scientific data have amply demonstrated that work stress increases the
      risk of cardiovascular disease. However, less attention has been given to the
      association between stress and metabolic syndrome. In this study, our aim was to
      investigate the relationship between work stress and metabolic syndrome in a
      population of radiologists. MATERIALS AND METHODS: Radiologists and
      radiotherapists taking part in scientific conferences were invited to compile a
      questionnaire to evaluate work stress and the main parameters for diagnosing
      metabolic syndrome (obesity, hypertension, elevated cholesterol level, elevated
      triglycerides, and hyperglycemia). RESULTS: Most of the doctors taking part in
      the survey (n = 383, 58.6 %) were found to have at least one pathological
      component; 47 subjects (7.1 %) had metabolic syndrome. All the variables
      indicating work stress, whether derived from Karasek's demand/control model or
      from the effort/reward model devised by Siegrist, were significant predictors of
      metabolic syndrome components. Radiologists with elevated levels of stress had a
      significantly higher risk of being affected by metabolic syndrome than colleagues
      with lower stress levels, whether stress was defined as "job strain", i.e.,
      elevated work load and reduced discretionary power (OR 4.89, 95 % CI 2.51-9.55),
      or as "effort reward imbalance", i.e., mismatch between effort and reward for the
      work performed (OR 4.66, 95 % CI 2.17-10.02). CONCLUSIONS: Should the results of
      this cross-sectional study be confirmed by a subsequent longitudinal survey, they
      would indicate the need for prompt organizational intervention to reduce
      occupational stress in radiologists.

PMID- 24297582
TI  - Imaging findings of hepatic focal nodular hyperplasia in men and women: are they
      really different?
AB  - PURPOSE: This study was undertaken to compare the imaging findings of focal
      nodular hyperplasia (FNH) in men and women, as seen on multidetector computed
      tomography (MDCT), magnetic resonance imaging (MRI) and contrast-enhanced
      ultrasound (CEUS). MATERIALS AND METHODS: Two radiologists reviewed 195 imaging
      studies (17 MDCT, 81 MRI and 97 CEUS examinations) pertaining to 111 FNHs (mean
      size 3 cm) in 91 patients (mean age 39 years). For each lesion, the readers
      assessed size, location, echogenicity, attenuation, or signal intensity in
      comparison with adjacent liver parenchyma on both unenhanced and postcontrast
      images. RESULTS: Eighty-nine FNHs (mean size 3.1 cm) were observed in 73 women
      (mean age 37.9 years) and 22 FNHs (mean size 2.7 cm) in 18 men (mean age 41.2
      years). No statistically significant differences were found between men and women
      in terms of age, FNH lesions per patient (1.22 and 1.21, respectively), size,
      baseline and enhancement pattern on MRI, CEUS and MDCT (p < 0.05). A central scar
      in FNHs was depicted in 4/18 (22.2%) men and 16/63 (25.4%) women on MRI (p <
      0.05), and in 1/2 (50%) men and 7/15 (46.7%) women on MDCT (p < 0.05), whereas a
      spoke-wheel pattern, central scar, and/or feeding vessel were seen in 5/17
      (29.4%) men and 22/80 (27.5%) women on CEUS (p < 0.05). CONCLUSIONS: Our results
      did not show any differences in imaging features, age of occurrence and size of
      FNH between men and women.

PMID- 24297581
TI  - Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging:
      response assessment after treatment with sorafenib: preliminary results.
AB  - PURPOSE: This study was undertaken to compare response evaluation criteria in
      solid tumours (RECIST) 1.1 and modified RECIST (mRECIST) in patients with
      unresectable hepatocellular carcinoma (HCC) on sorafenib, and to describe HCC
      enhancement changes before and after sorafenib treatment. METHODS AND MATERIALS:
      Seventeen patients (12 men, 5 women; mean age 69 years; age range 58-79 years)
      were included. Tumour response was assessed according to RECIST and mRECIST. Two
      readers placed a region of interest (ROI) within each target lesion, on the
      portion showing enhancement during the arterial phase. The lesion attenuation
      values measured within the ROIs on computed tomography or the signal intensity
      measured on magnetic resonance imaging, during the unenhanced phase, hepatic
      arterial phase and venous phase were recorded. Changes in arterial and venous
      contrast enhancement before and after treatment were compared among the mRECIST
      groups using Mann-Whitney U test. RESULTS: Agreement between mRECIST and RECIST
      was good (Cohen's k coefficient, 0.791). Patients with partial response had a
      greater decrease in arterial enhancement (-79.8%) than did patients with stable
      disease (SD) (-24.8%; p = 0.011) or progressive disease (PD) (-32.9%; p = 0.034).
      No statistically significant difference in arterial enhancement variation was
      found among patients with SD and PD. No statistically significant difference in
      venous enhancement was found among the mRECIST groups. CONCLUSIONS: mRECIST
      showed a more favourable response compared to RECIST 1.1 in patients with
      unresectable HCC receiving sorafenib.

PMID- 24297583
TI  - How to improve MRI accuracy in detecting deep infiltrating colorectal
      endometriosis: MRI findings vs. laparoscopy and histopathology.
AB  - OBJECTIVE: To verify whether the capability of magnetic resonance imaging (MRI)
      in diagnosing deep infiltrating colorectal endometriosis (DICE) is improved using
      an association of MRI findings. METHODS AND MATERIALS: The imaging database of
      our Institute of Radiology was retrospectively reviewed to identify patients
      subjected to MRI for a suspicion of deep infiltrating endometriosis. Medical
      history was then investigated and only patients who were also subjected to
      laparoscopy (LA) were included. Absence of LA represented the exclusion
      criterion. Images were evaluated twice by two radiologists using two different
      diagnostic criteria for an abnormal result: the contemporary presence of nodules
      or hypointense plaque-like lesions in the adjacent fat plane and bowel wall
      thickness, without (first criterion) or with (second criterion) semicircular
      shape (i.e. "radial and retracting shape"). Radiologists worked in consensus
      evaluating images in two separate sessions, using the first criterion in the
      first section and the second criterion in the second one. MRI results were
      compared with LA or histopathology as the gold standard by 2 * 2 tables and
      statistically analyzed (k statistics). Likelihood-ratio test was also performed,
      being independent from the prevalence of the disease. RESULTS: By consulting case
      sheets, 33/50 females (ranging age 24-39 years, mean age 32.2 years) who were
      subjected to MRI also underwent LA. Intestinal resection for DICE was performed
      in 11/33 patients; in 22/33 superficial intestinal foci, adhesions/nodules in the
      fat plane were simply removed. When the first criterion was applied, MRI
      agreement with histopathology or LA was poor (51.5 %) (k value = 0.20; p <
      0.055), while it was improved (96.9 %) when using the second diagnostic criterion
      (k value = 0.93; p < 0.0000). Likelihood ratio was 1.375 (95 % CI 0.69-2.72)
      using the first and 22 (95 % CI 20.08-24.1) using the second criterion.
      CONCLUSION: The second criterion, or the joint presence of nodules or hypointense
      plaque-like lesions in the adjacent fat plane and bowel wall thickness showing
      "radial and retracting shape", improves MRI capability in DICE diagnosis. It can
      be considered an effective indicator of DICE on T2-weighted images at 1.5-T MRI,
      and can ensure the correct preoperative assessment of the disease for the best
      therapeutic procedure and treatment planning.

PMID- 24297584
TI  - Comparison between different imaging techniques in the evaluation of malignant
      breast lesions: can 3D ultrasound be useful?
AB  - PURPOSE: This study was done to assess the feasibility of three-dimensional
      ultrasonography (3D-US) for volume calculation of solid breast lesions. MATERIALS
      AND METHODS: The volumes of 36 malignant lesions were measured using conventional
      2D-US, 3D-US and magnetic resonance imaging (MRI) and compared with that obtained
      with histology (standard of reference). With 2D Ultrasouns, volume was estimated
      by measuring three diameters and calculating volume with the mathematical formula
      for spheres. With 3D-US, stored images were retrieved and boundaries of masses
      were manually outlined; volume calculation was performed with VOCAL software. For
      MRI, volume measurements were obtained with special software for 3D
      reconstructions, after each lesion had been manually outlined. Histology measured
      the three main diameters and the volume was estimated using the mathematical
      formula for spheres. Interclass correlation coefficient (ICC) and Bland-Altman
      plots were used to assess agreement between the volumes measured. RESULTS: ICC
      indicated that a good level of concordance was identified between 3D-US and
      histology (0.79). According to the Bland-Altman analysis, limits of agreement of
      mean differences of the volumes measured with the three imaging modalities were
      comparable with histology: -2 / 1.5 cm(3) for 3D-US; -2.3 / 1.3 cm(3) for 2D-US
      and -2.2 / 1.6 cm(3) for MRI. CONCLUSIONS: 3D-US is a reliable method for the
      volumetric assessment of breast lesions. 3D-US is able to provide valuable
      information for the preoperative evaluation of lesions.

PMID- 24297585
TI  - In vivo differences among scan modes in bone mineral density measurement at dual
      energy X-ray absorptiometry.
AB  - PURPOSE: Our aim was to estimate the in vivo reproducibility of bone mineral
      density (BMD) at dual-energy X-ray absorptiometry (DXA) and to compare fast
      array, array, and high-definition scan modes. MATERIALS AND METHODS: A total of
      378 patients (38 males and 340 females; mean age 63 +/- 9 years) underwent DXA
      using a QDR-Discovery A densitometer (Hologic). Considering the three scan modes
      on lumbar spine and right femur, six independent groups of 30 patients were
      examined twice (for a total of 180 patients). Least significant change (LSC) and
      smallest detectable difference (SDD) were calculated. The remaining 198 patients
      underwent three scans of the lumbar spine (n = 92) or of the right femur (n =
      106), one for each scan mode. The student t test and Bland-Altman analysis used
      were. Scan times were recorded and radiation dose was estimated using the ICRP60
      method. RESULTS: Intra-scan mode reproducibility was 98-99%, corresponding to an
      LSC of 1.49-2.08%. The SDD was 0.018-0.023 g/cm(2) (lumbar spine) and 0.017-0.019
      g/cm(2) (right femur). All comparisons among scan modes were statistically
      significant (p < 0.001) but lower than SDDs, i.e. not clinically relevant.
      Considering lumbar spine and the right femur, scan times were 50 and 38 s for
      fast array, 98 and 74 s for array, and 195 and 148 s for high definition,
      respectively; radiation doses were 6.7 and 4.7 MUSv for fast array, and 13.3 and
      9.3 MUSv for both array and high definition, respectively. CONCLUSION: Since all
      BMD differences were lower than the SSDs, the three scan modes can be considered
      interchangeable. As a consequence, although the absolute reduction in time and
      radiation dose is relatively low, when BMD measurement is the aim of DXA, fast
      array can be generally preferred.

PMID- 24297586
TI  - Transcatheter embolisation of iatrogenic renal vascular injuries.
AB  - PURPOSE: The aim of our study was to review our experience and long-term follow
      up in the treatment of iatrogenic renal vascular injuries using transcatheter
      embolisation. MATERIALS AND METHODS: Our retrospective analysis of cases
      collected in two interventional centres consists of a total of 21 patients who
      underwent renal arterial embolisation (RAE) for iatrogenic arterial kidney
      bleeding. Biopsy (n = 4), percutaneous nephrolithotomy (n = 4), nephron-sparing
      surgery (n = 4), guidewire-induced arterial perforation during coronary
      angiography or renal stenting (n = 3), percutaneous nephrostomy (n = 3), renal
      endopyelotomy/pyeloplasty (n = 2) and surgical nephrectomy were the iatrogenic
      causes. Seven patients presented with haemodynamic instability requiring blood
      transfusion (33.3%), the remaining were haemodynamically stable (66.7%).
      Diagnostic renal angiography revealed 9 actively bleeding vessels, 6
      pseudoaneurysms, 4 arteriovenous fistulas and 1 arterio-calyceal fistula. In one
      patient selective renal arteriography was negative probably because the bleeding
      observed at CT angiography was self-limited. Twenty-one embolisation procedures
      were performed in 20 patients; one patient required a second embolisation 3 h
      after the first one. Embolisation was performed with microcoils, polyvinyl
      alcohol particles, embospheres, spongostan emulsion and vascular plug. RESULTS:
      The technical success rate was 100%. The overall clinical success rate was 95%.
      Apart from a patient who died due to disseminated intravascular coagulation, no
      major complications requiring intensive care treatment were encountered during or
      after the procedures. No patient required emergency surgery or subsequent
      surgical treatment. No statistically significant differences in eGFR or renal
      function stage appeared after RAE. CONCLUSIONS: Percutaneous treatment can be
      proposed as a first-line treatment in iatrogenic renal arterial injuries,
      resulting in a safe and effective procedure.

PMID- 24297587
TI  - Radiotherapy in low-grade glioma adult patients: a retrospective survival and
      neurocognitive toxicity analysis.
AB  - PURPOSE: The treatment of low-grade glioma is still debated. Surgery is the first
      line approach, and the correct timing of radiation therapy has not yet been
      defined since "early" radiation therapy improves relapse-free survival but not
      overall survival. Since a longer progression-free survival is desirable, the main
      issue related to radiotherapy is the incidence of late neurocognitive toxicity.
      MATERIALS AND METHODS: Ninety-five patients with low-grade glioma were
      consecutively treated with early (within 3 months) or late (at disease
      progression) post-surgical radiation therapy. Clinical and therapeutic factors
      were entered into the analysis overall (OS) and progression-free (PFS) survival,
      and the distribution in two accrual periods identified based on the evolution of
      imaging procedures and radiotherapy techniques were compared. For 6/18 long
      survivors (LS) without evidence of disease, neurocognitive evaluation was
      obtained and the dose to the hippocampus region was retrospectively calculated.
      RESULTS: Univariate analysis of OS showed a statistically significant advantage
      for grade 1 and oligodendroglioma histology, better performance status [Karnofsky
      index (KI)], age <40 years, radical surgery, no steroid treatment; PFS was
      significantly related with younger age, better KI and "early" radiotherapy.
      Multivariate analysis of OS confirmed the significance of all variables except
      surgery; for PFS, only "early" radiotherapy and better KI retained significance.
      Memory impairment was evident in 4/6 of the LS tested; quality of life was good
      and executive functions were normal. CONCLUSION: Radiotherapy remains an
      essential component in the treatment of low-grade glioma. Prospective studies are
      needed to evaluate the relative contributions of the disease itself and of
      surgery, radiation and chemotherapy to long-term neurocognitive damage.

PMID- 24297588
TI  - Ultrasound-guided interventional procedures around the shoulder.
AB  - The aim of this review is to illustrate the spectrum of ultrasound-guided
      procedures around the shoulder. The shoulder is affected by a wide range of both,
      traumatic and degenerative diseases. Ultrasound guidance is a low-cost and safe
      tool to perform minimally invasive interventional procedures around the shoulder.
      The clinical outcome is shown by the use of clinical scores: visual analogue
      scale (VAS), Constant's score and Shoulder Pain Disability Index (SPADI). Rotator
      cuff calcification is a common painful condition that occurs in up to 7.5 % of
      otherwise healthy adults. Ultrasound-guided procedures include single-needle and
      double-needle approach with different needles. These techniques are described and
      the results are critically compared. Ultrasound-guided viscosupplementation is a
      new therapeutic approach for treatment of several shoulder pain disorders:
      osteoarthritis, rotator cuff tear and tendinosis. In adhesive capsulitis,
      different therapeutic ultrasound-guided techniques such as corticosteroid
      injection, capsular distension (sodium chlorate solution; sodium chlorate and
      corticosteroids; air) and viscosupplementation are evaluated. Acromion-clavear
      injection of steroid and lidocaine solution under ultrasound guidance is easy to
      perform and is indicated in conservative treatment of painful osteoarthrosis. The
      treatment of rotator cuff tendinosis and partial tears with ultrasound-guided
      injection of concentrated autologous platelets is also described. 

PMID- 24297589
TI  - Radiofrequency thermal ablation (RFA) of hepatic metastases (METS) from breast
      cancer (BC): an adjunctive tool in the multimodal treatment of advanced disease.
AB  - PURPOSE: The study was done to analyse the results of a series of radiofrequency
      ablation (RFA) procedures performed on hepatic metastases (METS) from breast
      cancer in order to evaluate the clinical impact of this therapy. MATERIALS AND
      METHODS: We analysed 45 patients (mean age 55 years) with 87 METS (mean size 23
      mm), in terms of adverse events (AE), complete ablation (CA) at initial follow-up
      assessment and during the subsequent follow-up (mean 30 months), time to
      progression, and survival. The correlation between local effectiveness and METS
      size was investigated. Possible predictors of 3-year survival, including the
      local effectiveness of RFA (complete ablation maintained at 1-year versus
      treatment failure) were analysed. RESULTS: Nine AE occurred (two major
      complications, 2.3 %). CA at initial follow-up was obtained in 90 %; 19.7 % CA
      relapsed, with a time to progression of 8 months. The difference between the mean
      diameter of maintained CA (22 mm) and that of the treatment failures (30 mm) was
      highly significant (p = 0.0005), as was the 30 mm threshold (p = 0.0062). Overall
      survival at 1-3 years was 90, 58 and 44 %. At univariate analysis, the local
      effectiveness of RFA did not reach statistical significance. CONCLUSION: RFA of
      hepatic METS from breast cancer has high local effectiveness in tumours up to 30
      mm, but it is not relevant in determining survival.

PMID- 24297590
TI  - Association of work-related stress with depression and anxiety in radiologists.
AB  - PURPOSE: Since radiologists and radiotherapists can be occupationally exposed to
      significant psychosocial risk factors, some may find themselves in a state of
      distress. The aim of this study was to investigate the association of work
      related stress with the presence of symptoms of anxiety, depression and
      psychological malaise and to evaluate the risk of psychic disorder in
      radiologists suffering from work-related stress. METHODS: A total of 654
      radiologists responded to our invitation to complete a questionnaire designed to
      evaluate work-related stress and associated medical conditions: the General
      Health Questionnaire and Goldberg's Anxiety and Depression scales. RESULTS:
      Scores on the anxiety, depression and psychological malaise scales rise with an
      increase in effort and over-commitment, while control and support exert a
      protective effect. In radiologists who are aware of an effort/reward imbalance,
      there is a marked increase in the risk of anxiety [odds ratio (OR) 14.14, 95 % CI
      9.15-21.86], depression (OR 7.00, 95 % CI 4.76-10.30) and psychic disorders (OR
      3.95, 95 % CI 2.62-9.57). Radiologists who perceive demand as excessive in
      relation to their power of control also have an increased risk of being anxious
      (OR 2.98, 95 % CI 2.05-4.31), depressed (OR 1.73, 95 % CI 1.21-2.48) and affected
      by psychic disorders (OR 2.26, 95 % CI 1.48-3.45) compared to fellow workers who
      are not in a state of distress. CONCLUSIONS: Outstanding technical progress has
      been made in the field of radiology which today plays an invaluable role in
      public health. Now a major effort must also be made to improve the mental
      wellbeing of radiologists, both in the interests of the workers themselves, and
      also in those of their patients and the quality of the treatment they have the
      right to receive.

PMID- 24297591
TI  - Typical and atypical pattern of pulmonary sarcoidosis at high-resolution CT:
      relation to clinical evolution and therapeutic procedures.
AB  - AIM: This study was done to evaluate the importance of high-resolution CT (HRCT)
      in defining pattern and extent of disease and establishing the clinical and
      therapeutic pathway in sarcoidosis. MATERIALS AND METHODS: A retrospective
      analysis of 56 patients with pulmonary involvement of sarcoidosis was performed.
      Two groups were identified: 39 patients exhibiting a typical HRCT pattern and 17
      patients with an atypical pattern. Inclusion criteria were the presence of
      radiological documentation (HRCT) of disease, clinical and radiological follow-up
      of 1 year and the beginning of any therapy within 1 month from the diagnosis.
      RESULTS: Among subjects not receiving therapy, the comparison between the two
      groups showed that the radiological findings remained stable in subjects with a
      typical pattern, while they worsened in more than 70% of cases with atypical
      appearance. Therapy was more effective in patients with a typical pattern.
      Recurrences occurred in both groups, but more often in patients with a typical
      pattern. One patient not receiving treatment experienced clinical worsening. Re
      evaluation of HRCT within 1 year revealed no correlation between clinical
      deterioration and radiological changes. CONCLUSIONS: The findings of this study
      suggest that persistence of the inflammatory process rather than the radiological
      pattern at onset is a prognostic factor for recurrence.

PMID- 24297592
TI  - Dilated Virchow-Robin spaces and multiple sclerosis: 3 T magnetic resonance
      study.
AB  - PURPOSE: The aim of this study was to assess differences in the presence, size,
      number and site of dilated cerebral Virchow-Robin spaces (VRSd) between patients
      with multiple sclerosis (MS) in the inactive phase and healthy controls, and
      between MS patients with disabling (MSd) or nondisabling (MSnd) disease.
      MATERIALS AND METHODS: The study was performed by retrospectively analysing the 3
      T magnetic resonance studies of 40 MS patients and 30 healthy subjects (matched
      for age, education and gender). The data were analysed with MIPAV (Medical Image
      Processing, Analysis and Visualisation) software to assess for VRSd and with FSL
      SIENA-X to measure global cerebral atrophy (GCA) expressed as brain parenchyma
      fraction. RESULTS: The MS patients had significantly higher VRSd number (p <
      0.011), area (p < 0.0073) and volume (p < 0.0071) than controls, with a marked
      increase for atypical sites (p < 0.0069) without significant intragroup
      differences between the disease forms (MSd vs MSnd). The number and size of VRSd
      did not correlate with GCA. CONCLUSIONS: Our results confirm previous reports
      regarding the increase in VRSd in nonactive phases of MS and support the
      immunological role of the VRS within the central nervous system. The lack of
      correlation between VRSd and the degree of GCA and their prevailing localisation
      in atypical sites in MS patients make VRSd a potential marker of inflammatory
      demyelinating disease.

PMID- 24297593
TI  - Cerebrovascular stenosis in neurofibromatosis type 1 and utility of magnetic
      resonance angiography: our experience and literature review.
AB  - PURPOSE: Neurofibromatosis type 1 (NF1) is a multisystem autosomal dominant
      disorder that primarily involves the skin and the nervous system. Development of
      cerebral arterial stenosis is a potentially deadly complication of NF1, which is
      frequently underestimated. The aim of our paper is to report the frequency of
      this cerebrovascular disease in a series of patients affected by NF1, using
      magnetic resonance angiography (MRA). A review of the literature was also
      performed, focused on the usefulness of MRA in NF1 patients. MATERIALS AND
      METHODS: Among 125 patients with NF1 (clinical diagnosis according to the
      standard National Institutes of Health criteria), 81 (65%) were studied with
      brain MRI (magnetic resonance imaging) and MRA using a 1.5 T magnet. RESULTS:
      Multiple intracranial arterial stenoses were found in six patients (7.4%). In our
      study, MRA proved to be critical, especially for the detection of stenoses in the
      branches of the Circle of Willis. CONCLUSION: Few case series have investigated
      the incidence of vascular complications of NF1, and most of them have used MRI.
      We suggest adding MRA to the brain imaging of all these patients, as stenoses of
      the branches of the Circle of Willis are often undetectable by MRI only.

PMID- 24297594
TI  - Trans-thoracic biopsy of lung lesions: FNAB or CNB? Our experience and review of
      the literature.
AB  - PURPOSE: This study was performed to determine the type and incidence of
      complications of fine-needle aspiration biopsy (FNAB) and core biopsy (CNB)
      performed under computed tomography (CT) guidance to characterise lung lesions,
      and assess the diagnostic accuracy of the two techniques. MATERIALS AND METHODS:
      In 2009-2011, we performed 124 lung biopsies (66 CNB and 56 FNAB) on 121 patients
      with a mean age of 72.4 years. Exclusion criteria were pulmonary resection,
      pleural lesions and/or effusions, and inadequate blood-coagulation profile. All
      examinations were acquired after contrast-agent administration in a craniocaudal
      direction from the lung apex to base during a single inspiratory breath-hold,
      with standardised parameters. Each lesion was scanned with 13-15 slices that
      could be repeated whenever necessary to document the needle track and for lesion
      centring, by positioning a metallic marker perpendicular to the centring light to
      indicate the point of needle access. Unless otherwise clinically indicated, 4 h
      after the procedure chest radiography was performed. RESULTS: Age was found to be
      a factor influencing the complications: pneumothorax in young subjects (31 %) and
      parenchymal haemorrhage in the elderly (30 %), with CNB but not with FNAB. We had
      more complications with the right lung: 50 % of pneumothorax cases in the upper
      lobe with CNB and 40 % of cases of haemorrhage in the lower lobe with FNAB. The
      anterior approach gave rise to more complications with CNB, while the posterior
      approach with FNAB. CNB had more complications than FNAB for lesions <= 3.5 cm
      (31 vs. 18 % pneumothorax), and >3.5 cm (34 vs. 9 % haemorrhage). There was no
      significant correlation with lesion histology, needle calibre or number of passes
      (probably due to the small number of procedures done with needles other than 18 G
      in CNB or 22 G in FNAB or involving more than one needle pass). The diagnostic
      accuracy of FNAB, done with a pathologist's extemporaneous assessment of sample
      adequacy, was 94.83 % against 81.82. % of CNB. CONCLUSIONS: FNAB under CT
      guidance is subject to a lower rate of complications and, if performed in the
      presence of the pathologist, has a greater diagnostic accuracy compared to CNB.

PMID- 24297595
TI  - Role of magnetic resonance imaging in probably benign (BI-RADS category 3)
      microcalcifications of the breast.
AB  - PURPOSE: This study was undertaken to evaluate whether magnetic resonance (MR)
      imaging is able to rule out malignancy in the case of BI-RADS 3
      microcalcifications, providing a sufficient negative predictive value (NPV) for
      early work-up, and to reduce unnecessary stereotactically guided vacuum-assisted
      biopsy (SVAB) procedures. MATERIALS AND METHODS: We prospectively enrolled
      consecutive women with BI-RADS 3 microcalcifications, who subsequently underwent
      MR imaging and SVAB. The MR studies were reviewed according to the MR-BI-RADS
      classification system; lesions assessed as MR-BI-RADS 1 and 2 were considered
      negative for malignancy, categories MR-BI-RADS 3, 4 and 5 indicated malignant
      lesions. The presence of additional findings was recorded. Histologic analysis
      and follow-up were the reference standard. MR sensitivity, specificity, positive
      predictive value (PPV) and NPV were calculated. RESULTS: The final population
      consisted of 71 lesions. Histologic analysis showed malignancy in six cases
      (malignancy rate 8%). At MR analysis, 60 (85%) lesions were considered negative
      for malignancy and 11 (15%) malignant. Additional MR imaging findings were
      identified in 19 (27%) patients, all corresponding to nonmalignant lesions. MR
      sensitivity was 33%, specificity 86%, PPV 18% and NPV 93%. CONCLUSIONS: Because
      of its relatively low NPV, MR imaging is not able to safely exclude malignancy in
      the case of BI-RADS 3 microcalcifications. The relatively high malignancy rate
      found in this study might support SVAB in the case of BI-RADS 3
      microcalcifications.

PMID- 24297596
TI  - Identification of left atrial fibrosis with a late-enhancement MR sequence (LE
      MR): preliminary results.
AB  - PURPOSE: This study was done to identify left atrial fibrosis in a group of
      consecutive patients with atrial fibrillation (AF) candidate for percutaneous
      radiofrequency catheter ablation (RFCA) by using a late-enhancement magnetic
      resonance (LE-MR) sequence, and to validate the technique by comparison with
      electroanatomical mapping (EAM). MATERIALS AND METHODS: We enrolled 37 patients
      (29 males; mean age, 61 years) candidate for percutaneous RFCA of AF, who were
      studied with LE-MR and EAM. To identify left AF we used a three-dimensional LE
      sequence with cardiac gating and respiratory navigator. The EAM study involved
      the acquisition of 200 points in the left atrium (LA). The LA was divided into
      seven segments (pulmonary vein antra, floor, anterior wall, posterior wall-roof).
      Two blinded radiologists assessed the presence of fibrosis (area of hyperintense
      signal), reaching a consensus in discordant cases. Inter-observer variability was
      also evaluated to estimate the reproducibility of the method. We analysed the
      anatomical agreement between the results obtained with LE-MR imaging and EAM.
      RESULTS: Five patients were excluded because of to poor image quality. As for the
      other 32 patients, inter-observer agreement was good [Cohen's kappa kappa = 0.72
      with 95 % confidence interval (CI) of 0.55, 0.89]. In the classification of LA
      segments affected by fibrosis, LE-MR had a sensitivity, specificity, positive
      predictive value, negative predictive value, and diagnostic accuracy of 66 % (95
      % CI 53.7 %, 77.2 %); 87 % (95 % CI 80.9 %, 91.9 %); 69 % (95 % CI 56.5 %, 80.1
      %); 85.5 % (95 % CI 79.1 %, 90.6 %) and 81 % (95 % CU 75.1 %, 85.7 %).
      CONCLUSIONS: Despite the small size of the sample studied, the LE-MR sequence
      proved more useful for excluding the presence of AF than for confirming its
      existence. Identification of AF prior to RFCA is paramount to select those
      patients who are truly amenable to the ablation procedure, which is expensive and
      not entirely free of risks.

PMID- 24297597
TI  - Pulmonary veno-occlusive disease: the role of CT.
AB  - OBJECTIVE: The authors sought to evaluate the diagnostic accuracy of high
      resolution computed tomography (HRCT) in the detection of pulmonary veno
      occlusive disease (PVOD) in patients with pre-capillary pulmonary arterial
      hypertension (PAH) of unknown aetiology, and to identify the role of CT in
      diagnosis and therapy. MATERIALS AND METHODS: The CT scans of 96 patients were
      retrospectively reviewed and assessed for specific HRCT findings: ground-glass
      opacities, septal lines and mediastinal lymph nodal enlargement (short diameter
      >=1 cm). According to the HRCT findings, patients were divided into PVOD
      suspicious and not PVOD-suspicious. Subsequently, a clinical-instrumental
      evaluation was performed, and the response to therapy and histopathological
      reports were evaluated. RESULTS: Radiological evaluation based on HRCT findings
      revealed 29 patients as PVOD-suspicious and 67 as not PVOD-suspicious. The final
      diagnosis was PVOD in 22 patients and idiopathic PAH in 74 patients. The CT scan
      showed 95.5 % sensitivity, 89% specificity, 72.5% positive predictive value, and
      98.5% negative predictive value, with a diagnostic accuracy of 90.5% in
      identifying patients with PVOD. CONCLUSIONS: Chest CT can be considered a
      screening test in the assessment of patients with PAH of unknown aetiology, and
      the radiologist can help the clinician to identify patients with CT findings that
      make PVOD highly probable.

PMID- 24297598
TI  - Gadoxetic acid-enhanced MRI for hepatocellular carcinoma and hypointense nodule
      observed in the hepatobiliary phase.
AB  - PURPOSE: The aim of our study was to evaluate the diagnostic accuracy of
      gadoxetic acid-enhanced magnetic resonance (MR) imaging both in the detection of
      hepatocellular carcinoma (HCC) and precancerous lesions and in the assessment of
      their evolution. MATERIALS AND METHODS: A retrospective study was undertaken on
      56 patients with chronic liver disease and suspected liver lesions. We evaluated
      the number, size and signal intensity of the nodules on dynamic and hepatobiliary
      MR images. Follow-up studies were carried out every 3 months. Statistical
      analysis was performed using the Fisher's exact test. RESULTS: A total of 120
      nodules were identified in 41 patients. Of these, 92/120 nodules (76.6%; mean
      diameter 18.4 mm) showed the typical HCC vascular pattern: 90/92 nodules appeared
      hypointense and 2/92 were hyperintense on hepatobiliary phase images. An
      additional 28/120 hypointense, nonhypervascular nodules (23.3%; mean diameter 11
      mm) were detected on hepatobiliary phase images, 15 of which showed hypointensity
      also on the equilibrium phase images. During the 3- to 12-month follow-up, 14/28
      nodules (mean diameter 13.3 mm) developed the typical vascular pattern of HCC.
      CONCLUSIONS: Gadoxetic acid-enhanced MR imaging is useful for detecting HCC as
      well as hypovascular nodules with potential progression to HCC. Lesions measuring
      more than 10 mm in diameter are at higher risk of developing into HCC (p =
      0.0128).

PMID- 24297599
TI  - Physicochemical characterization of 9-aminocamptothecin in aqueous solutions.
AB  - The present manuscript provides a detailed physicochemical and thermodynamic
      characterization of 9-aminocamptothecin (9AC) which can be used as a tool to
      develop novel formulation strategies for optimum pharmacological activity. The
      pKa of 9AC was determined to be 2.43 at 37 degrees C, while the basicity of
      quinoline nitrogen of 9AC was found to decrease with increasing temperature due
      to a positive enthalpy of deprotonation of 10.36 kJ mol(-1). The equilibrium
      solubility as well as the intrinsic solubility of the drug was found to increase
      with increasing temperature and decreasing pH. The enthalpies of solution of
      unionized and ionized forms of 9AC obtained from isothermal and iso-pH
      equilibrium solubility measurements were found to be 36.01 and 24.72 kJ mol(-1),
      respectively. Equilibrium hydrolysis studies revealed the hydrolytic
      susceptibility of 9AC with only 14% of active lactone species remaining at
      physiological pH 7.4. The intrinsic partition coefficient log P of the free base,
      9AC-lactone, was estimated to be 1.28 (a characteristic of molecules suitable for
      oral absorption). The estimated pKa and log P values of 9AC, combined with its
      increased solubility at lower pH, are features that can be utilized to develop
      novel drug delivery systems to optimize the antitumor activity of 9AC.

PMID- 24297600
TI  - Release characteristics of quetiapine fumarate extended release tablets under
      biorelevant stress test conditions.
AB  - The aim of the present work was the investigation of robustness and reliability
      of drug release from 50 to 400 mg quetiapine extended release HPMC matrix tablets
      towards mechanical stresses of biorelevant intensity. The tests were performed
      under standard conditions (USP apparatus II) as well as under simulated
      gastrointestinal stress conditions. Mechanical stresses including pressure and
      agitation were applied by using the biorelevant dissolution stress test apparatus
      as it has been introduced recently. Test algorithms already established in
      previous studies were applied to simulate fasting gastrointestinal conditions.
      The dissolution experiments demonstrated striking differences in the product
      performance among standard and stress test conditions as well as dose strengths.
      In USP apparatus II, dissolution profiles were affected mainly by media pH. The
      dissolution experiments performed in biorelevant dissolution stress test device
      demonstrated that stress events of biorelevant intensity provoked accelerated
      drug release from the tablets.

PMID- 24297601
TI  - Maternal smoking during pregnancy and the risk of childhood type 1 diabetes in
      Western Australia.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the association between
      maternal smoking during pregnancy and type 1 diabetes in the offspring, using
      complete population data sources available in Western Australia. METHODS: A
      prospective cohort study was undertaken with cases defined as children born in
      Western Australia between 1998 and 2008 who were diagnosed with type 1 diabetes
      at <15 years of age up to 31 December 2010. Eligible cases were identified from
      the prospective, population-based Western Australian Children's Diabetes
      Database. Record linkage was performed to identify perinatal records of cases
      from the Western Australian Midwives' Notification System, which contains data on
      >99% of all births in Western Australia. Cox regression was used to analyse the
      data and adjust for recognised risk factors such as birthweight, gestational age,
      maternal age and socioeconomic status. RESULTS: The unadjusted HR for babies born
      to mothers who smoked during pregnancy being diagnosed with childhood type 1
      diabetes was 0.70 (95% CI: 0.50, 0.97). After adjustment, the confidence interval
      widened but the point estimate remained relatively unchanged at 0.76 (95% CI:
      0.54, 1.08). CONCLUSIONS/INTERPRETATION: Analyses of data from this population
      based study indicate that maternal smoking during pregnancy may be associated
      with a reduced risk of childhood type 1 diabetes. Further investigation in larger
      populations with more detailed smoking data could lead to novel hypotheses
      regarding mechanisms that influence the immunopathogenesis of type 1 diabetes in
      early life.

PMID- 24297602
TI  - Gd(3+) complexes conjugated to Pittsburgh compound B: potential MRI markers of
      beta-amyloid plaques.
AB  - In an effort towards the visualization of beta-amyloid (Abeta) plaques by T1
      weighted magnetic resonance imaging for detection of Alzheimer's disease, we
      report the synthesis and characterization of stable, noncharged Gd(3+) complexes
      of three different 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide
      derivatives conjugated to Pittsburgh compound B, a well-established marker of
      Abeta plaques. The ligands L1, L2, and L3 differ in the nature and size of the
      spacer linking the macrocyclic chelator and the Pittsburgh compound B targeting
      moiety, which affects their lipophilicity, the octanol-water partition
      coefficients of the complexes ranging from -0.15 to 0.32. Given their amphiphilic
      behavior, the complexes form micelles in aqueous solution (critical micellar
      concentration 1.00-1.49 mM). The parameters determining the relaxivity, including
      the water exchange rate and the rotational correlation times, were assessed for
      the monomeric and the micellar form by a combined (17)O NMR and (1)H nuclear
      magnetic relaxation dispersion (NMRD) study. They are largely influenced by the
      aggregation state and the hydrophobic character of the linkers. The analysis of
      the rotational dynamics for the aggregated state in terms of local and global
      motions using the Lipari-Szabo approach indicates highly flexible, large
      aggregates. On binding of the complexes to human serum albumin or to the amyloid
      peptide Abeta1-40 in solution, they undergo a fourfold and a twofold relaxivity
      increase, respectively (40 MHz). Proton relaxation enhancement studies confirmed
      moderate interaction of Gd(L1) and Gd(L3) with human serum albumin, with KA
      values ranging between 250 and 910 M(-1).

PMID- 24297603
TI  - Methylobacterium pseudosasae sp. nov., a pink-pigmented, facultatively
      methylotrophic bacterium isolated from the bamboo phyllosphere.
AB  - A pink-pigmented, Gram negative, aerobic, facultatively methylotrophic bacterium,
      strain BL44(T), was isolated from bamboo leaves and identified as a member of the
      genus Methylobacterium. Phylogenetic analysis based on 16S rRNA gene sequences
      showed similarity values of 98.7-97.0 % with closely related type strains and
      showed highest similarity to Methylobacterium zatmanii DSM 5688(T) (98.7 %) and
      Methylobacterium thiocyanatum DSM 11490(T) (98.7 %). Methylotrophic metabolism in
      this strain was confirmed by PCR amplification and sequencing of the mxaF gene
      coding for the alpha-subunit of methanol dehydrogenase. Strain BL44(T) produced
      three known quorum sensing signal molecules with similar retention time to C8,
      C10 and C12-HSLs when characterized by GC-MS. The fatty acid profiles contained
      major amounts of C18:1 omega7c, iso-3OH C17:0 and summed feature 3 (C16:1 omega7c
      and/or iso-C15:0 2-OH), which supported the grouping of the isolate in the genus
      Methylobacterium. The DNA G+C content was 66.9 mol%. DNA relatedness of the
      strain BL44(T) to its most closely related strains ranged from 12-43.3 %. On the
      basis of the phenotypic, phylogenetic and DNA-DNA hybridization data, strain
      BL44(T) is assigned to a novel species of the genus Methylobacterium for which
      the name Methylobacterium pseudosasae sp. nov. is proposed (type strain BL44(T) =
      NBRC 105205(T) = ICMP 17622(T)).

PMID- 24297604
TI  - Dysregulation of microRNA expression drives aberrant DNA hypermethylation in
      basal-like breast cancer.
AB  - Basal-like breast cancers frequently express aberrant DNA hypermethylation
      associated with concurrent silencing of specific genes secondary to DNMT3b
      overexpression and DNMT hyperactivity. DNMT3b is known to be post
      transcriptionally regulated by microRNAs. The objective of the current study was
      to determine the role of microRNA dysregulation in the molecular mechanism
      governing DNMT3b overexpression in primary breast cancers that express aberrant
      DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a,
      miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR
      26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers
      (36 luminal A-like, 13 luminal B-like, 5 HER2-enriched, 16 basal-like) and 18
      normal mammoplasty tissues. Significantly reduced expression of miR-29c
      distinguished basal-like breast cancers from other breast cancer molecular
      subtypes. The expression of aberrant DNA hypermethylation was determined in a
      subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched
      and 16 basal-like) through examination of methylation-sensitive biomarker gene
      expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33
      (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal
      like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1;
      HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express
      diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b
      compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%)
      basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished
      levels of >=6 regulatory miRs. The results show that i) reduced expression of miR
      29c is characteristic of basal-like breast cancers, ii) miR and methylation
      sensitive gene expression patterns identify two subsets of basal-like breast
      cancers, and iii) the subset of basal-like breast cancers with reduced expression
      of multiple regulatory miRs express aberrant DNA hypermethylation. Together,
      these findings strongly suggest that the molecular mechanism governing the DNMT3b
      mediated aberrant DNA hypermethylation in primary breast cancer involves the loss
      of post-transcriptional regulation of DNMT3b by regulatory miRs.

PMID- 24297606
TI  - The impulsivity and sensation-seeking mediators of the psychological consequences
      of pathological gambling in adolescence.
AB  - Pathological gambling has severe consequences for adolescents and their families
      and friends. Despite its high prevalence, pathological gambling in adolescents
      has been insufficiently studied. Sensation seeking and impulsivity are two
      variables that are related to the appearance and maintenance of pathological
      gambling. However, few studies have determined the role these variables play in
      the development of the dysfunctional symptomatology of gambling behavior in
      adolescents and young adults. The aims of this study were to analyze the
      consequences of gambling in young adults and adolescents, and to evaluate the
      roles of sensation seeking and impulsivity in the appearance of dysfunctional
      symptomatology. The sample consisted of 1,241 young adults and adolescents
      recruited from scholar centers and free-time groups, as well as 71 subjects from
      associations that assist pathological gamblers. Pathological gambling, impulsive
      behavior, dysfunctional symptomatology and sensation seeking were assessed. The
      results confirmed that young adults and adolescents who gamble pathologically
      have more dysfunctional symptomatology related to anxiety, depression, hostility,
      obsessive-compulsive behavior and somatization, as well as sensation seeking,
      impulsivity and addictive behavior. Moreover, the results showed that sensation
      seeking did not mediate the appearance of dysfunctional symptomatology and that
      impulsivity partially mediated the appearance of anxiety, phobic anxiety,
      depression and psychosis and perfectly mediated somatization, obsessive
      compulsive behavior, interpersonal sensitivity, paranoid ideation and hostility.
      These results have consequences for the development of treatment and prevention
      programs for adolescent pathological gambling. 

PMID- 24297607
TI  - Analysis of counts with two latent classes, with application to risk assessment
      based on physician-visit records of cancer survivors.
AB  - Motivated by a cancer survivorship program, this paper explores event counts from
      two categories of individuals with unobservable membership. We formulate the
      counts using a latent class model and consider two likelihood-based inference
      procedures, the maximum likelihood estimation (MLE) and a pseudo-MLE procedure.
      The pseudo-MLE utilizes additional information on one of the latent classes. It
      yields reduced computational intensity and potentially increased estimation
      efficiency. We establish the consistency and asymptotic normality of the proposed
      pseudo-MLE, and we present an extended Huber sandwich estimator as a robust
      variance estimator for the pseudo-MLE. The finite-sample properties of the two
      parameter estimators along with their variance estimators are examined by
      simulation. The proposed methodology is illustrated by physician-claim data from
      the cancer program. 

PMID- 24297608
TI  - Treatment of displaced talar neck fractures using delayed procedures of plate
      fixation through dual approaches.
AB  - PURPOSE: Treatment of talar neck fractures is challenging. Various surgical
      approaches and fixation methods have been documented. Clinical outcomes are often
      dissatisfying due to inadequate reduction and fixation with high rates of
      complications. Obtaining satisfactory clinical outcomes with minimum
      complications remains a hard task for orthopaedic surgeons. METHODS: In the
      period from May 2007 to September 2010, a total of 31 cases with closed displaced
      talar neck fractures were treated surgically in our department. Injuries were
      classified according to the Hawkins classification modified by Canale and Kelly.
      Under general anaesthesia with sufficient muscle relaxation, urgent closed
      reduction was initiated once the patients were admitted; if the procedure failed,
      open reduction and provisional stabilisation with Kirschner wires through an
      anteromedial approach with tibiometatarsal external fixation were performed. When
      the soft tissue had recovered, definitive fixation was performed with plate and
      screws through dual approaches. The final follow-up examination included
      radiological analysis, clinical evaluation and functional outcomes which were
      carried out according to the Ankle-Hindfoot Scale of the American Orthopaedic
      Foot and Ankle Society (AOFAS), patient satisfaction and SF-36. RESULTS: Twenty
      eight patients were followed up for an average of 25 months (range 18-50 months)
      after the injury. Only two patients had soft tissue complications, and recovery
      was satisfactory with conservative treatment. All of the fractures healed
      anatomically without malunion and nonunion, and the average union time was 14
      weeks (range 12-24 weeks). Post-traumatic arthritis developed in ten cases, while
      six patients suffered from avascular necrosis of the talus. Secondary procedures
      included three cases of subtalar arthrodesis, one case of ankle arthrodesis and
      one case of total ankle replacement. The mean AOFAS hindfoot score was 78 (range
      65-91). According to the SF-36, the average score of the physical component
      summary was 68 (range 59-81), and the average score of the mental component
      summary was 74 (range 63-85). CONCLUSIONS: Talar neck fractures are associated
      with a high incidence of long-term disability and complications. Urgent reduction
      of the fracture-dislocation and delayed plate fixation through a dual approach
      when the soft tissue has recovered may minimise the complications and provide
      good clinical outcomes.

PMID- 24297609
TI  - The outcome of open elbow arthrolysis: comparison of four different approaches
      based on one hundred cases.
AB  - PURPOSE: The aim of this study was to evaluate the results of elbow arthrolysis
      according to the surgical approach, durability after arthrolysis and the severity
      of contracture. METHODS: The study includes a cohort of 100 consecutive patients
      treated in our institution between 1986 and 2008. The indication for surgery was
      loss of mobility. This was the result of fractures, dislocation, simultaneous
      fracture/dislocation or other non-traumatic causes. All patients underwent open
      elbow release via one of four approaches (42 lateral, 44 medial, six combined
      medial-lateral and eight posterior). They were clinically evaluated at a minimum
      of 24 months after arthrolysis. RESULTS: The average ranges of elbow extension,
      flexion and arc of motion had increased significantly at the follow up,
      respectively, by 20 degrees , 16 degrees  and 36 degrees . No significant
      difference was found with regard to surgical approach. However, we noticed
      significant deterioration of intra-operative average extension and arc of motion
      (AOM) over the follow up period, respectively, by 13 degrees  and 14 degrees .
      The number of patients with AOM of 100 degrees  or more increased from three
      patients preoperatively to 28 postoperatively. CONCLUSIONS: Open elbow
      arthrolysis is a successful method of treatment of elbow contracture. Results are
      durable, but there is some postoperative deterioration of extension gained during
      surgery. We may anticipate that at the final stage we shall obtain an average of
      86% of intra-operative arc of motion. Patients with the most severe contractures
      have the best gains.

PMID- 24297610
TI  - Setting standards for medical writing in orthopaedics.
AB  - Once the privilege of few clinical scholars in the field of orthopaedics, medical
      writing has become a must for career advancement. The number of papers submitted
      and published yearly has increased steadily, and with the development of the
      Internet, manuscript and journals have become easily accessible. Medical writing
      has risen to become a discipline in itself, with rules and standards. However,
      heterogeneity in the quality of papers submitted still prevails, with large
      variations in both form and content. With countries such as China and India
      submitting an exponential number of manuscripts, it is important and helpful that
      standards of medical writing be emphasised to help writers who do not always have
      the required support to produce an outstanding manuscript. In this paper, we
      summarise what may become standards for medical writing in the field of
      orthopaedics. 

PMID- 24297611
TI  - Relationship of plasma and synovial fluid vascular endothelial growth factor with
      radiographic severity in primary knee osteoarthritis.
AB  - PURPOSE: Recent evidence suggests that angiogenesis and inflammation contribute
      to the development and progression of osteoarthritis (OA). The purpose of this
      study was to investigate vascular endothelial growth factor (VEGF) levels in
      plasma and synovial fluid of patients with knee OA and to determine the
      relationship of VEGF levels with disease severity in knee OA. METHODS: A total of
      100 subjects were enrolled in this study (80 knee OA patients and 20 healthy
      controls). Plasma and synovial fluid VEGF levels were analysed using enzyme
      linked immunosorbent assay. VEGF expressions in synovial membrane and articular
      cartilage samples were assessed using immunohistochemistry. RESULTS: VEGF level
      in synovial fluid of knee OA patients was tenfold higher than that in paired
      plasma (P < 0.001). Both plasma and synovial fluid VEGF exhibited a positive
      correlation with radiographic severity (r = 0.454 and r = 0.727, P < 0.001,
      respectively). VEGF expression was highly detectable in synovial lining cells and
      articular chondrocytes of knee OA patients. CONCLUSIONS: VEGF levels in both
      plasma and synovial fluid were positively correlated with the severity of knee
      OA. Therefore, VEGF may be useful for monitoring OA severity and could play a
      substantial role in the development and progression of knee OA.

PMID- 24297612
TI  - Inhibition of the Hedgehog pathway induces autophagy in pancreatic ductal
      adenocarcinoma cells.
AB  - The HH signaling pathway is a 'core' signal transduction pathway in pancreatic
      cancer that promotes the tumorigenesis of pancreatic cancers via enhancing cell
      proliferation, increasing invasion and metastasis and protecting against
      apoptosis. In the present study, we found that HH signaling regulates autophagy
      in pancreatic cancer cells. Activation of HH signaling inhibits autophagy, while
      inhibition of the HH pathway induces autophagy. Although the role of autophagy in
      cell survival and apoptosis may depend on tumor type and the microenvironment,
      our data clearly demonstrated that GANT61-induced autophagy contributed to
      reduced viability and increased apoptosis in pancreatic cancer cells both in vivo
      and in vitro, and these effects were reversed by the autophagy inhibitor, 3-MA.
      We propose that HH signaling by regulating autophagy plays an important role in
      determining the cellular response to HH-targeted therapy in pancreatic cancer and
      further investigation of the interaction between autophagy and HH signaling is
      particularly important.

PMID- 24297613
TI  - Why talk with children matters: clinical implications of infant- and child
      directed speech research.
AB  - This article reviews basic features of infant- or child-directed speech, with
      particular attention to those aspects of the register that have been shown to
      impact profiles of child language development. It then discusses concerns that
      arise when describing adult input to children with language delay or disorder, or
      children at risk for depressed language skills. The article concludes with some
      recommendations for parent counseling in such cases, as well as methods that
      speech-language pathologists can use to improve the quality and quantity of
      language input to language-learning children. 

PMID- 24297614
TI  - Input and language development in bilingually developing children.
AB  - Language skills in young bilingual children are highly varied as a result of the
      variability in their language experiences, making it difficult for speech
      language pathologists to differentiate language disorder from language difference
      in bilingual children. Understanding the sources of variability in bilingual
      contexts and the resulting variability in children's skills will help improve
      language assessment practices by speech-language pathologists. In this article,
      we review literature on bilingual first language development for children under 5
      years of age. We describe the rate of development in single and total language
      growth, we describe effects of quantity of input and quality of input on growth,
      and we describe effects of family composition on language input and language
      growth in bilingual children. We provide recommendations for language assessment
      of young bilingual children and consider implications for optimizing children's
      dual language development. 

PMID- 24297615
TI  - How gesture input provides a helping hand to language development.
AB  - Children use gesture to refer to objects before they produce labels for these
      objects and gesture-speech combinations to convey semantic relations between
      objects before conveying sentences in speech--a trajectory that remains largely
      intact across children with different developmental profiles. Can the
      developmental changes that we observe in children be traced back to the gestural
      input that children receive from their parents? A review of previous work shows
      that parents provide models for their children for the types of gestures and
      gesture-speech combinations to produce, and do so by modifying their gestures to
      meet the communicative needs of their children. More importantly, the gestures
      that parents produce, in addition to providing models, help children learn labels
      for referents and semantic relations between these referents and even predict the
      extent of children's vocabularies several years later. The existing research thus
      highlights the important role parental gestures play in shaping children's
      language learning trajectory.

PMID- 24297616
TI  - Input and language development in children with autism.
AB  - The social deficits associated with autism spectrum disorders (ASD) have been
      implicated in the language delays and deficits of children with ASD.
      Consequently, the extent to which children with ASD utilize their language
      related interactions and input in the same ways as typically developing children
      is only just beginning to be investigated. The current article summarizes the
      role of input for typically developing children learning language, and then
      reviews in some detail recent studies demonstrating influential effects of
      maternal responsivity (e.g., following in on children's focus of attention) and
      aspects of maternal speech (e.g., word frequency, word diversity, structural
      complexity) on the language production and comprehension of young children with
      ASD. Maternal responsivity appears to play a particularly influential role with
      children who are minimally verbal whereas the content and structure of maternal
      speech facilitate language in children who are already verbal. 

PMID- 24297618
TI  - Decontextualized language input and preschoolers' vocabulary development.
AB  - This article discusses the importance of using decontextualized language, or
      language that is removed from the here and now including pretend, narrative, and
      explanatory talk, with preschool children. The literature on parents' use of
      decontextualized language is reviewed and results of a longitudinal study of
      parent decontextualized language input in relation to child vocabulary
      development are explained. The main findings are that parents who provide their
      preschool children with more explanations and narrative utterances about past or
      future events in the input have children with larger vocabularies 1 year later,
      even with quantity of parent input and child prior vocabulary skill controlled.
      Recommendations for how to engage children in decontextualized language
      conversations are provided.

PMID- 24297617
TI  - Father input and child vocabulary development: the importance of Wh questions and
      clarification requests.
AB  - Individual differences in children's language skills have been shown to stem in
      part from variations in the quantity and quality of parent speech input. However,
      most research focuses on mothers' input whereas less is known about the effects
      of variability in father input. In this article, we review the relation between
      parent input and child language development with a focus on low-income families,
      and review general findings about similarities and differences in mother and
      father speech. Within this review, we highlight conversation-eliciting speech,
      such as wh questions and clarification requests, which occur, on average, more
      frequently in father input than mother input. Conversation-eliciting speech is
      challenging for 2-year-old children and has been shown in research with mothers
      to relate to child vocabulary development. We then report a study examining
      whether fathers' use of conversation-eliciting speech relates to children's
      developing vocabulary skills at 24 months of age within a sample of low-income
      African American families. Understanding that speech input varies among fathers,
      and specific strengths that fathers bring to interactions with their young
      children can help speech-language pathologists develop and implement more
      effective interventions. 

PMID- 24297619
TI  - Parent-directed approaches to enrich the early language environments of children
      living in poverty.
AB  - Children's early language environments are critical for their cognitive
      development, school readiness, and ultimate educational attainment. Significant
      disparities exist in these environments, with profound and lasting impacts upon
      children's ultimate outcomes. Children from backgrounds of low socioeconomic
      status experience diminished language inputs and enter school at a disadvantage,
      with disparities persisting throughout their educational careers. Parents are
      positioned as powerful agents of change in their children's lives, however, and
      evidence indicates that parent-directed intervention is effective in improving
      child outcomes. This article explores the efficacy of parent-directed
      interventions and their potential applicability to the wider educational
      achievement gap seen in typically developing populations of low socioeconomic
      status and then describes efforts to develop such interventions with the Thirty
      Million Words Project and Project ASPIRE (Achieving Superior Parental Involvement
      for Rehabilitative Excellence) curricula. 

PMID- 24297620
TI  - Modeling simple driving tasks with a one-boundary diffusion model.
AB  - A one-boundary diffusion model was applied to the data from two experiments in
      which subjects were performing a simple simulated driving task. In the first
      experiment, the same subjects were tested on two driving tasks using a PC-based
      driving simulator and the psychomotor vigilance test. The diffusion model fit the
      response time distributions for each task and individual subject well. Model
      parameters were found to correlate across tasks, which suggests that common
      component processes were being tapped in the three tasks. The model was also fit
      to a distracted driving experiment of Cooper and Strayer (Human Factors, 50, 893
      902, 2008). Results showed that distraction altered performance by affecting the
      rate of evidence accumulation (drift rate) and/or increasing the boundary
      settings. This provides an interpretation of cognitive distraction whereby
      conversing on a cell phone diverts attention from the normal accumulation of
      information in the driving environment. 

PMID- 24297621
TI  - Persecutory delusions and psychological well-being.
AB  - PURPOSE: Persecutory delusions are one of the key problems seen in psychotic
      conditions. The aim of the study was to assess for the first time the levels of
      psychological well-being specifically in patients with current persecutory
      delusions. METHOD: One hundred and fifty patients with persecutory delusions in
      the context of a diagnosis of non-affective psychosis, and 346 non-clinical
      individuals, completed the Warwick-Edinburgh Mental Well-Being Scale and symptom
      assessments. RESULTS: Well-being scores were much lower in the persecutory
      delusions group compared with the non-clinical control group. 47 % of the
      persecutory delusions group scored lower than two standard deviations below the
      control group mean score. Within the patient group, psychological well-being was
      negatively associated with depression, anxiety, and hallucinations. In both
      groups, lower levels of well-being were associated with more severe paranoia.
      CONCLUSIONS: Levels of psychological well-being in patients with current
      persecutory delusions are strikingly low. This is likely to arise from the
      presence of affective symptoms and psychotic experiences. Measurement of
      treatment change in positive mental health for patients with psychosis is
      recommended.

PMID- 24297622
TI  - Negative symptoms mediate the influence of theory of mind on functional status in
      schizophrenia.
AB  - We aimed to assess the relationship between social cognition, neurocognition,
      negative symptoms and functional status in a homogeneous schizophrenia patient
      group remitted from positive symptoms. Sixty patients underwent assessments of
      social and neurocognition dimensions recommended by expert panels. A blind rater
      assessed their functional status. Second order theory of mind (ToM) and negative
      symptoms had significant correlations with functional status. A bootstrapping
      analysis used to test for specific mediation models revealed that the effect of
      second order ToM on functioning was mediated by negative symptoms. Future studies
      should examine if targeted remediation of ToM improves negative symptoms and thus
      functioning. 

PMID- 24297623
TI  - Biological characteristics and epidermal growth factor receptor tyrosine kinase
      inhibitors efficacy of EGFR mutation and its subtypes in lung adenocarcinoma.
AB  - Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be
      present in lung adenocarcinoma (LAC). In this study, we extensively investigated
      the impact of patients' biological characteristics on EGFR mutation and the
      impact of EGFR mutation subtypes on targeted therapy of advanced LAC. We examined
      EGFR exons18to21status in169 LAC patients by direct sequencing to study the
      impact of patients' biological characteristics on the EGFR mutational spectrum.
      And then, 59 patients with advanced LAC harboring EGFR exon 19 deletions(del 19)
      or exon 21 point mutation(L858R) mutations received first-line treatment of
      gefitinib or erlotinib, the efficacy of treatment, and the progression-free
      survival (PFS) of these patients were recorded. The frequency of the EGFR
      mutation and its subtypes and the variables associated with the EGFR mutation
      after removing the confound factors were investigated by the logistic analysis
      using all samples (n = 169). The EGFR mutation was significantly associated with
      well-differentiated tumor and excessive household cooking fumes(P < 0.05). The
      deletions in exon 19 were more frequently associated with well-differentiated
      tumor (P < 0.05). The overall frequency of the EGFR mutation was 49 %. Then the
      impact of EGFR mutation subtypes on targeted therapy were investigated by the
      retrospective analysis on 59 advanced LAC patients with del 19 or L858R mutations
      and treated first-line with erlotinib or gefitinib. The deletions in exon 19 got
      longer PFS (P < 0.05). But there were no differences in PFS between erlotinib
      therapy and gefitinib therapy. EGFR mutations were more frequently in high tumor
      differentiation and excessive household cooking fumes LAC. The del 19 mutation
      rate is relatively high with a high differentiation degree in advanced lung
      adenocarcinoma. The deletions in exon 19 may benefit more from first-line
      targeted therapy of advanced LAC compared with exon 21 point mutation L858R.
      There was no significant difference between the efficacy of gefitinib and
      erlotinib treatments associated with EGFR mutation and its subtypes.

PMID- 24297625
TI  - Segregation of signaling proteins as prognostic predictors for local recurrence
      and distant metastasis in hepatocellular carcinoma.
AB  - Postoperative recurrence of hepatocellular carcinoma (HCC) is presented as local
      recurrence (LR) or extrahepatic metastasis (EHM). Recent studies indicated that
      EHM requires additional cellular alterations. This study aimed to examine the
      clinical and molecular prognostic predictors of these two events. HCC patients
      (289) [training cohort (n=160) and verification cohort (n=129)] receiving
      surgical resection of hepatomas were included. The expression levels of six
      signaling molecules were quantitatively assessed for prognostic analysis.
      Clustering analysis revealed similar expression profiles between cancer (T) and
      non-cancer (N) liver tissues in the same individuals. Univariate analysis showed
      that phosphorylated mammalian target of rapamycin (mTOR)-T was associated with LR
      free survival (P=0.002), whereas extracellular signal-related kinase (ERK2)-T
      (P=0.005), AKT-T (P=0.001) and glycogen synthase kinase (GSK)-T/N ratio (P=0.008)
      were associated with EHM-free survival. When clinical predictors were added for
      multivariate analysis, only prolonged prothrombin time (P=0.003) and tumor number
      (P=0.031) was independently associated with LR-free survival, whereas age
      (P=0.019), creatinine levels (P=0.001) and AKT-T (P=0.004) were associated with
      EHM-free survival. These factors were further examined in the verification
      cohort. In conclusion, postoperative LR and EHM in HCC were associated with
      separable sets of clinical and molecular predictors. 

PMID- 24297626
TI  - Influential factors in bisphosphonates for periprosthetic bone loss after total
      joint arthroplasty.

PMID- 24297627
TI  - Difficulty in locking head screw removal.
AB  - BACKGROUND: Locking plates are an internal fixation material useful in the
      treatment of bone fractures, which provides effective stabilization between the
      plate and locking head screws (LHSs) via the locking mechanism. However,
      difficulty in removing LHSs is relatively common, and such cases can require long
      surgical procedures or use of special removal equipment. The purpose of this
      study was to report the incidence and risk factors for difficult removal of LHSs.
      METHODS: During the 5-year-6-month period from April 2006 to September 2011, 83
      locking plates containing a total of 482 LHSs were removed in 80 patients at our
      institution. Out of 482 LHSs, there were 118 LHSs with a 2.4-2.7 mm diameter, 308
      LHSs with a 3.5 mm diameter and 56 LHSs with a 5.0 mm diameter. The incidence of
      removal difficulty was examined on the basis of screw diameter. In addition, the
      risk factors were assessed in only LHSs with a 3.5 mm diameter. LHSs with a 3.5
      mm diameter were divided into 2 groups, the difficult removal group and the easy
      removal group, and the data were examined based on age, sex, time between
      insertion and removal, and screw position. The incidence of removal difficulty in
      LHSs with a 3.5 mm diameter was examined every 6 months between insertion and
      removal. RESULTS: Difficulty in removal was encountered in none (0 %) of 118 LHSs
      with a 2.4-2.7 mm diameter, 15 (4.9 %) of 308 LHSs with a 3.5 mm diameter, and
      none (0 %) of 56 LHSs with a 5.0 mm diameter. In only LHSs with a 3.5 mm
      diameter, the mean ages of the patients in the difficult removal group and the
      easy removal group were 32.1 and 45.6 years, respectively. The average time
      between insertion and removal in the difficult removal group and the easy removal
      group was 529.2 and 389.2 days, respectively. There was a statistically
      significant difference in age and time between insertion and removal. Removal was
      difficult in 15 (9.1 %) of 165 LHSs with a 3.5 mm diameter in those with >1 year
      between insertion and removal. CONCLUSION: This study suggests that (1) the use
      of LHSs with a 3.5 mm diameter is a necessary condition for difficulty in screw
      removal, and that (2) longer time from internal fixation to removal, and (3)
      younger age, are risk factors for it. When removing LHSs with a 3.5 mm diameter,
      appropriate instruments and sufficient training are necessary.

PMID- 24297629
TI  - Oil Red O-assessed macrosteatosis in liver transplant donor biopsies predicts
      ischemia-reperfusion injury and clinical outcome.
AB  - Steatosis in donor livers is an accepted adverse prognostic factor after liver
      transplantation. While its semiquantitative assessment shows varying
      reproducibility, it is questioned as a standard method. Additionally, the
      influence of hepatic steatosis on ischemia/reperfusion injury (I/R injury) has
      not been evaluated in biopsies after reperfusion. We compared different staining
      and analyzing methods for the assessment of donor liver steatosis in order to
      predict I/R injury and clinical outcome after transplantation. To do this, 56
      paired pre- and post-reperfusion liver biopsies were analyzed for macro-
      (MaS)/micro- (MiS) and total steatosis in cryo and permanent sections by special
      fat (Oil Red O or ORO) and standard stains. Computerized morphometrical analyses
      were compared to the semiquantitative assessment by a pathologist. I/R injury was
      determined histopathologically and by M30 immunohistochemistry. We found ORO to
      be more sensitive in detecting hepatic steatosis with higher reproducibility for
      MaS. Semiquantitative analyses were highly reproducible and not inferior to
      computerized morphometry. Categorized MaS as determined by ORO correlated with
      the extent of I/R injury, initial poor function, liver enzymes, and survival.
      Therefore fat stains like ORO are a reliable and easy method comprising
      significant advantages in the evaluation of hepatic steatosis and are thereby of
      prognostic value. Computerized analysis is a precise tool though not superior to
      semiquantitative analyses. 

PMID- 24297630
TI  - A rare congenital extrahepatic portosystemic shunt affecting the inferior
      mesenteric vein, inferior vena cava, and left ovarian vein.
AB  - PURPOSE: To observe a case of congenital extrahepatic portosystemic shunt and
      discuss it from the embryological and clinical viewpoints. METHODS: An 85-year
      old female cadaver was employed for a dissection course at Aichi Medical
      University in 2009. RESULTS: There was no evidence of liver cirrhosis
      macroscopically or microscopically. A portosystemic shunt was observed that
      involved communication between the inferior mesenteric vein, inferior vena cava
      (IVC), and left ovarian vein by a single Y-shaped shunt vessel. CONCLUSIONS: To
      the best of our knowledge, this is the first reported case of the above-mentioned
      three veins being connected by a single Y-shaped shunt vessel. Considering the
      other venous diameters, the shunt appeared to flow into the splenic vein and IVC.
      It cannot be denied that this shunt may have led to hepatic encephalopathy,
      although the shunt effect may have been minimal. Embryological development of IVC
      appears to occur close to the plexus of anastomosing vitelline veins, forming the
      portal vein.

PMID- 24297631
TI  - A specific instrument to facilitate thoracoscopic ligation.
AB  - The rigid wall of the thoracic cavity provides an ideal cavity for minimally
      invasive surgery without the need for the cumbersome CO2 insufflation that is
      essential to perform laparoscopic surgery. And by that, the novel ligation
      technique facilitating minithoracotomy, which we published before, is possible to
      be transferred to the video-assisted thoracoscopic surgery (VATS). We attempt to
      modify the structure of the conventional right angle forceps and its usage so as
      to accommodate VATS. The unique shape of this instrument facilitates its passage
      through a trocar or a true VATS intercostal access instead of a rib spreading
      minithoracotomy. Its clinical performance renders that it a cheaper and better
      alternative to commercially available products. This new device has the potential
      to make a substantial contribution to the manual ligation practice of VATS. 

PMID- 24297632
TI  - Does video-assisted mediastinoscopy offer lower false-negative rates for
      subcarinal lymph nodes compared with standard cervical mediastinoscopy?
AB  - OBJECTIVES: Theoretically, video-assisted mediastinoscopy (VAM) offers improved
      staging of subcarinal lymph nodes (LNs) compared with standard cervical
      mediastinoscopy (SCM). Materials and METHODS: Between 2006 and 2011, 553 patients
      (SCM, n = 293; VAM, n = 260) with non-small cell lung carcinoma who underwent
      mediastinoscopy were investigated. Mediastinoscopy was performed only in select
      patients based on computed tomography (CT) or positron emission tomography CT
      scans in our center. RESULTS: The mean number of LNs and stations sampled per
      case was significantly higher with VAM (n = 7.65 +/- 1.68 and n = 4.22 +/- 0.83)
      than with SCM (n = 6.91 +/- 1.65 and 3.92 +/- 86.4; p < 0.001). The percentage of
      patients sampled in station 7 was significantly higher with VAM (98.8%) than with
      SCM (93.8%; p = 0.002). Mediastinal LN metastasis was observed in 114 patients by
      mediastinoscopy. The remaining 439 patients (203 patients in VAM and 236 in SCM)
      underwent thoracotomy and systematic mediastinal lymphadenectomy (SML). SML
      showed mediastinal nodal disease in 23 patients (false-negative [FN] rate, 5.2%).
      The FN rate was higher with SCM (n = 14, 5.9%) than with VAM (n = 9, 4.4%),
      although this difference was not statistically significant (p = 0.490). Station 7
      was the most predominant station for FN results (n = 15). The FN rate of station
      7 was found to be higher with SCM (n = 9, 3.8%) than with the VAM group (n = 6,
      2.9%; p = 0.623). CONCLUSION: FN were more common in mediastinoscopy of
      subcarinal LNs. VAM allows higher rates of sampling of mediastinal LN stations
      and station 7, although it did not improve staging of subcarinal LNs.

PMID- 24297633
TI  - Efficacy assessment of the drainage with permanent airflow measurement in the
      treatment of pneumothorax with air leak.
AB  - AIM: The aim of this study was to compare the efficacy of the treatment of
      patients with spontaneous pneumothorax with air leak (AL) using two different
      chest drainage systems. METHODS: Patients were randomized into two groups: group
      A included 30 patients (23 males and 7 females, mean age 41.1 +/- 16.29 y, range
      17-71 y) in which digital drainage system was used, group B with 30 patients (22
      males and 8 females, mean age 40.3 +/- 15.74 y, range 18-72 y) in which
      traditional suction drainage system was applied.The following variables were
      evaluated: intensity of AL, duration of the chest tube drainage, delay in
      surgery, length of stay, and the overall hospitalization costs. RESULTS: In group
      A the mean drainage duration was 47.63 hours, the hospitalization time was about
      5.10 days, and the cost of hospitalization was ?1,495. In group B the mean
      drainage duration was 84.93 hours, the hospitalization time was 6.97 days, and
      the hospitalization cost was ?1,925. CONCLUSION: The digital drainage system
      applied in the treatment of AL in patients with pneumothoraces reduced the
      duration of the drainage, the length of hospital stay, and overall
      hospitalization costs.

PMID- 24297634
TI  - Laser resection of lung tissue: heat accumulation from adjacent laser application
      and how to cool it down.
AB  - BACKGROUND: Heat accumulation might induce thermal damage of the surrounding lung
      tissue, especially when multiple lesions are resected in one session. The present
      study aimed to investigate whether heat accumulates in the immediate vicinity of
      the resection surface and leads to thermal damage of the lung parenchyma, and
      what is the most effective cooling strategy in this situation. MATERIALS AND
      METHODS: In normothermic perfused paracardial swine lobes (n = 6), four
      punctiform laser lesions forming a square were created. Each lesion was lasered
      at a power of 100 W for 5 seconds. Two test conditions with square sides of
      either 1.0 or 0.5 cm were compared. Temperatures were recorded immediately after
      completing the laser procedure in the square center and in the corners using a
      thermal camera and continued during the cooling process at 10-second intervals
      until normothermia (37 degrees C). We examined two cooling methods: rinsing with
      ice-cold (4 degrees C) Ringer solution during the laser procedure (group B, n =
      6) or submerging the lung in ice-cold water for 5 seconds immediately after laser
      application (group C, n = 6). In the control group A (n = 6), there was no
      cooling. RESULTS: In the 0.5 cm squares, mean temperature in the center
      immediately after laser application was 103.17 +/- 8.56 degrees C, significantly
      higher than in the corners (76.39 +/- 2.87 degrees C, p < 0.05). Normothermia in
      the quadrant corners was reached after 81 +/- 14 and after 108 +/- 29 seconds in
      the centers. Tissue in the square center revealed histological signs of thermic
      cell damage. In the 1.0 cm squares, mean temperature in the center was 64 +/- 5
      degrees C, and in the corners was 77 +/- 3.1 degrees C (p < 0.05). Normothermia
      was regained after 93 +/- 22 seconds in the center and 120 +/- 21 seconds in the
      corners. Histological examination in the 1.0-quadrant centers revealed no signs
      of thermic cell damage. Submerging the lobe into ice-cold water lowered the
      temperature rapidly to under 40 degrees C, and normothermia was regained after 75
      +/- 1.3 seconds. CONCLUSION: Laser application to the lung parenchyma causes
      considerable heat accumulation in closely related lesions. To prevent such cell
      damage, a distance of at least 1.0 cm between laser targets should be maintained.
      If no topical cooling method applied, sufficient time for spontaneous tissue
      cooling before additional laser application should be provided. The most
      effective cooling strategy against heat accumulation is submerging in ice-cold
      water for at least 5 seconds.

PMID- 24297635
TI  - The influence of serum sodium concentration on prognosis in resected non-small
      cell lung cancer.
AB  - BACKGROUND: Hyponatremia is the most common electrolyte disorder and is a
      negative prognostic factor in several kinds of cancer. However, few reports have
      referred to hyponatremia in non-small cell lung cancer (NSCLC). In the present
      study, the authors examined the influence of preoperative serum sodium
      concentration on survival in completely resected NSCLC. METHODS: A total of 386
      completely resected NSCLC patients were retrospectively analyzed. RESULTS: Kaplan
      Meier survival curves showed that serum sodium concentration was a significant
      prognostic factor, and the log-rank statistical value was maximum (9.173, p =
      0.002) when the cutoff value of serum sodium concentration was 139 mEq/L. The
      overall 5-year survival rate of the high-serum sodium concentration group (> 139
      mEq/L) was 74.8% and that of the low-serum sodium concentration group (<= 139
      mEq/L) was 59.7%. Clinicopathological factors showed significant differences
      between the two groups for leukocyte count, neutrophil count, C-reactive protein,
      tumor size, and pleural invasion. CONCLUSIONS: Low-serum sodium concentration,
      which was associated with tumor status and inflammation, had negative prognostic
      influence in completely resected NSCLC.

PMID- 24297636
TI  - Is a vessel-sealing system useful for resection of anterior mediastinal mass?
AB  - OBJECTIVE: To valuate if the LigaSure (Valleylab, Boulder, Colorado, United
      States) vessel-sealing system could reduce operative time, intraoperative blood
      loss, drainage duration, and hospital stay in patients with anterior mediastinal
      mass undergoing open resection. METHODS: Forty consecutive patients having
      resection of anterior mediastinal mass were randomized into two groups according
      to whether LigaSure was used (n = 20) or not (n = 20). Tumor size, operative
      time, intraoperative blood loss, chest tube output and duration, length of
      hospital stay, morbidity, and mortality were prospectively recorded, then
      intergroup differences were statistically analyzed. RESULTS: Both groups were
      well matched for age, tumor size, pathologic diagnosis, and incidence of
      complications. LigaSure significantly reduced operative duration (p < 0.0001)
      compared with the traditional technique but without leading to any significant
      reduction in intraoperative blood loss (p = 0.2), chest tube output (p = 0.2) and
      duration (p = 0.2), and length of hospital stay (p = 0.5). CONCLUSIONS: The
      reduced operative time using LigaSure translates into less exposure to general
      anesthesia, which is particularly important for patients with myasthenia and
      potentially reducing cost.

PMID- 24297637
TI  - The MitraClip System: a systematic review of indications, procedural
      requirements, and guidelines.
AB  - BACKGROUND: Transcatheter interventions (TIs) are new treatment options for
      patients with severe mitral valve regurgitation (MR) who cannot undergo open
      mitral valve surgery (oMVS). Despite the lack of scientific evidence
      demonstrating the benefit of these procedures, there has been a steady increase
      in their use. The aim of this study was to evaluate whether there are any
      indication criteria, process, and structural requirements, or scientific society
      and institutional guidelines for the use of the MitraClip System (Abbott Vascular
      Structural Heart, Menlo Park, California, United States). METHOD: A systematic
      literature search was conducted using the common medical and scientific
      databases. Of a total of 1,395 publications, 42 publications met the inclusion
      criteria and were included for the evaluation. RESULTS: Despite a general lack of
      high-quality evidence and of consensus recommendations from scientific societies
      or institutions, an assessment of indication criteria and process and structural
      requirements for the use of the MitraClip System, including noncontrolled
      studies, was possible. The majority of studies agree that an interdisciplinary
      heart team including a cardiothoracic surgeon, an interventional cardiologist,
      and an echocardiographic specialist should actively participate in clinical
      decision making, and in the procedure itself. Participation in a scientific-based
      registry is strongly recommended. CONCLUSIONS: The MitraClip System is a
      promising procedure, but evidence-based indication criteria, structural, and
      process requirements for its use are lacking. Further results from prospective,
      randomized controlled trials are needed to determine patients, potential adverse
      events, device durability, and long-term follow-up. MitraClip should be used in
      only a small number of centers with procedure-specific, high-quality surgical and
      interventional experience, and training.

PMID- 24297638
TI  - TRAP1 role in endoplasmic reticulum stress protection favors resistance to
      anthracyclins in breast carcinoma cells.
AB  - Adaptation to endoplasmic reticulum (ER) stress through the upregulation of the
      ER chaperone BiP/Grp78 favors resistance of cancer cells to anthracyclins. We
      recently demonstrated that the mitochondrial HSP90 chaperone TNF receptor
      associated protein 1 (TRAP1) is also localized in the ER, where it is responsible
      for protection from ER stress and quality control on specific mitochondrial
      proteins contributing to its anti-apoptotic function and the regulation of the
      mitochondrial apoptotic pathway. Based on the evidence that Bip/Grp78 and TRAP1
      are co-upregulated in about 50% of human breast carcinomas (BCs), and considering
      that the expression of TRAP1 is critical in favoring resistant phenotypes to
      different antitumor agents, we hypothesized that ER-associated TRAP1 is also
      favoring resistance to anthracyclins. Indeed, anthracyclins induce ER stress in
      BC cells and cross-resistance between ER stress agents and anthracyclins was
      observed in bortezomib- and anthracyclin-resistant cells. Several lines of
      evidence suggest a mechanistic link between the ER-stress protecting function of
      TRAP1 and resistance to anthracyclins: i) ER stress- and anthracyclin-resistant
      cell lines are characterized by the upregulation of TRAP1; ii) TRAP1 silencing in
      both drug-resistant cell models restored the sensitivity to bortezomib and
      anthracyclins; iii) the transfection of a TRAP1 deletion mutant, whose
      localization is restricted to the ER, in TRAP1 KD cells protected from apoptosis
      induced by anthracyclins; iv) the disruption of the ER-associated TRAP1/TBP7
      pathway by a TBP7 dominant negative deletion mutant re-established drug
      sensitivity in drug-resistant cells. This process is likely mediated by the
      ability of TRAP1 to modulate the PERK pathway as TRAP1 KD cells failed to induce
      the phosphorylation of PERK in response to anthracyclins. Moreover, the
      downregulation of TRAP1 in combination with ER stress agents produced high
      cytotoxic effects in BC cells. These results suggest that ER-associated TRAP1
      plays a role in protecting tumor cells against DNA damaging agents by modulating
      the PERK pathway.

PMID- 24297639
TI  - A monocarbonyl analogue of curcumin, 1,5-bis(3-hydroxyphenyl)-1,4-pentadiene-3
      one (Ca 37), exhibits potent growth suppressive activity and enhances the
      inhibitory effect of curcumin on human prostate cancer cells.
AB  - Prostate carcinoma is one of the leading causes of cancer-related morbidity and
      mortality in males in western countries. Curcumin exhibits growth-suppressive
      activity against several cancers, including prostate cancer, but it has poor
      bioavailability. The purpose of this study was to evaluate the anticancer potency
      and mechanism of a curcumin analogue, 1,5-bis(3-hydroxyphenyl)-1,4-pentadiene-3
      one (Ca 37), in human prostate cancer. Studies were performed in established
      human prostate cancer cell lines (PC-3 and DU145) as well as in a murine
      xenograft tumor (PC-3) model. Ca 37 presented a preferential suppression capacity
      against growth and migration toward prostate cancer cells compared with curcumin.
      Ca 37 impaired the bioenergetics system, promoted cell cycle arrest and apoptosis
      activation in PC-3 cells. In addition, 0.5 MUmol (6.65 mg/kg body weight) of Ca
      37 significantly inhibited the growth of the prostate xenografted tumors, whereas
      6 MUmol (110 mg/kg body weight) of curcumin had little effect. Furthermore, a
      combination of Ca 37 and curcumin resulted in enhanced antitumor activity in
      prostate cancer cells. N-Acetylcysteine abrogated both reactive oxygen species
      (ROS) production and viability loss induced by Ca 37 but partially prevented
      growth inhibition in PC-3 cells treated with curcumin alone, or a combination
      with Ca 37. The data indicate that induction of ROS plays a vital role in the
      growth inhibitory effect of Ca 37 in PC-3 cells. This study suggests that Ca 37,
      alone or in combination with curcumin, may be a promising anticancer agent for
      prostate cancer therapy.

PMID- 24297640
TI  - Effects of cadmium, copper and zinc on growth of four isolated algae from a
      highly polluted Argentina river.
AB  - Toxicity of cadmium, copper and zinc was tested on four green algal species
      (Ankistrodesmus fusiformis, Chlorella ellipsoidea, Monoraphidium contortum and
      Scenedesmus acuminatus) isolated from a highly polluted river (Matanza-Riachuelo
      River, Buenos Aires, Argentina). The relative abundance of these species in river
      waters showed that C. ellipsoidea was the most abundant species (mean 4,540 ind
      mL(-1)), whereas the less abundant species was S. acuminatus (mean 220 ind mL(
      1)). The most sensitive species was A. fusiformis, which EC50 were Cd = 141 MUg
      L(-1), Cu = 72 MUg L(-1), and Zn = 199 MUg L(-1), whereas C. ellipsoidea was the
      most resistant species to copper (EC50 = 489 MUg L(-1)) and cadmium (EC50 = 429
      MUg L(-1)), and M. contortum and S. acuminatus were the most resistant species to
      zinc (EC50 = 381 and 394 MUg L(-1), respectively).

PMID- 24297641
TI  - Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus
      erythematosus--a case report.
AB  - Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric
      systemic lupus erythematosus (NPSLE), under some circumstances it appears to be
      difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or
      by other reasons such as primary mental disorders or substance-induced mood
      disorders, especially induced by glucocorticoids or antimalarials. We report the
      case of a male patient with SLE who presented with an exacerbation of bipolar
      disorder triggered by chloroquine. Firstly, when the patient was diagnosed with
      SLE, he underwent six months of therapy with chloroquine without any psychiatric
      symptoms. Later, the SLE returned and the patient was prescribed chloroquine
      again, without any mental illness. When the third exacerbation of SLE occurred,
      it coincided with a severe depressive episode with psychotic features that became
      aggravated for the first time after the administration of chloroquine. The
      chloroquine was subsequently replaced with hydroxychloroquine for the next six
      months without any behavioral problems, following which, the SLE and mood
      disorder were in remission. Later, a bipolar disorder relapse occurred,
      manifested by a manic episode, and in the following three months, despite
      psychiatric treatment, a manic episode with psychotic features developed four
      days after chloroquine was prescribed for arthritis. It was the second time that
      the mood disorder was exacerbated by chloroquine. Since that time, chloroquine
      has been withdrawn. Currently the patient is undergoing treatment with
      hydroxychloroquine and psychiatric drugs with good response. Our case points out
      that although chloroquine-induced psychosis is rare, patients presenting with
      behavioral changes need physicians' attention in order to diagnose early and
      efficiently treat encountered mood disorders. 

PMID- 24297642
TI  - Associations of clinical features and prognosis with age at disease onset in
      patients with systemic lupus erythematosus.
AB  - The objective of this study is to evaluate the association of clinical features
      and prognosis with age at disease onset in patients with systemic lupus
      erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of
      1898 SLE inpatients from 15 hospitals were reviewed and classified into three
      groups according to their ages at disease presentation. Categorical data were
      analyzed by chi-square test and potentially associated factors were tested by
      multinomial logistic regression. Among the patients studied, 259 (13.6%) were
      juvenile onset (<=18 years), 1444 (76.1%) were early onset (>18 and <=45 years)
      and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred,
      most patients (>80%) were diagnosed within two years. Juvenile-onset patients
      were more likely to be untreated before admission (p < 0.001) and have
      mucocutaneous manifestations (p < 0.001), but musculoskeletal symptoms (p < 0.05)
      and leukopenia (p < 0.05) were less frequent, while comorbidities were much
      higher in patients with late-onset SLE (p < 0.001). Neuropsychiatric,
      cardiopulmonary, renal and gastrointestinal involvement, disease activity index
      and damage scores were similar among three groups. Anti-Sm antibodies were less
      prevalent in late-onset patients (p < 0.05) and antimalarial drugs were more
      often applied to juvenile-onset patients (p < 0.001). As expected, mortality was
      elevated in the late-onset SLE group (p < 0.05), in which nearly half died of
      infections, which was much higher than those in the other two groups (p < 0.001).
      Logistic regression confirmed that patients with juvenile- and early-onset
      disease were associated with high incidence of being untreated prior to
      admission, and with low incidence of comorbidities as well as deaths caused by
      infection compared to patients with late-onset lupus. Interestingly, our data
      showed that more patients with late-onset disease had a SLEDAI score change of >7
      at discharge. In conclusion, age at onset has an impact on SLE disease status,
      and infection is the main cause of death in those with late-onset lupus.
      Considering that the late-onset patients had simultaneously easily controllable
      diseases and high incidence of comorbidities, a different treatment strategy from
      younger patients should be considered. 

PMID- 24297643
TI  - Kidney allograft survival of African American and Caucasian American recipients
      with lupus.
AB  - BACKGROUND: African Americans with lupus who receive kidney transplants have high
      prevalence of predictors of allograft failure, which can explain their poor
      outcomes. METHODS: Of 1223 African Americans and 1029 Caucasian Americans with
      lupus who received kidney transplants from deceased donors between 1987 and 2006
      with complete records in the UNOS program, 741 pairs were matched in 16
      predictors employing a predicted probability of group membership. The primary
      outcome was allograft failure. Main secondary outcomes were rejection, allograft
      failure due to rejection, and mortality. RESULTS: Matched pairs were
      predominantly women (82%) with a mean age of 39 years. Twenty-four percent of
      recipients received kidneys from expanded criteria donors. African Americans and
      Caucasian Americans matched well (p >= 0.05): donor age, gender and race;
      recipient age, gender, education and insurance; dialysis prior to transplant,
      kidneys from expanded criteria donors, cold ischemia time, history of prior
      kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch,
      blood type compatibility, transplant Era, and follow-up time. Contrary to the
      unmatched cohort with significantly higher allograft failure rate (events per 100
      patient-years) in African Americans compared to Caucasian Americans (10.49 vs
      6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81,
      p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39,
      p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and
      mortality (2.79 vs 3.52, p=0.097). CONCLUSION: In lupus recipients of kidney
      transplants from deceased donors, African American and Caucasian Americans have
      similar allograft failure rates when predictors are matched between groups.

PMID- 24297644
TI  - Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant
      human urothelial carcinoma cells.
AB  - Survivin is overexpressed in transitional cell carcinoma (TCC), the most common
      type of bladder cancer. Previous reports demonstrated that knockdown of survivin
      by siRNA induced apoptosis of TCC cells. The present study evaluated the
      therapeutic effects of sepantronium bromide (YM155), a novel small molecule
      survivin inhibitor under clinical trials, on TCC cells in vitro. BFTC905, a grade
      III TCC cell line derived from a patient of blackfoot disease in Taiwan, was the
      most gemcitabine-resistant cell line when compared to BFTC909, TSGH8301 and T24
      in cytotoxicity assay, resulting from upregulation of securin and bcl-2 after
      gemcitabine treatment. YM155 caused potent concentration-dependent cytotoxicity
      in 4 TCC cell lines (IC50s <=20 nM), but exhibited no cytotoxicity in survivin
      null primary human urothelial cells. For BFTC905 cells, addition of gemcitabine
      and/or cisplatin, the standard TCC chemotherapy regimen, to YM155 did not exert
      additive cytotoxic effects. Molecular analyses indicated that YM155 inhibited the
      proliferation of BFTC905 cells by increasing p27kip1, suppressing Ki-67, and
      inducing quiescence. In addition, YM155 elicited apoptosis manifested with DNA
      fragmentation through suppressing the expression of survivin, securin and bcl-2.
      Furthermore, YM155 induced autophagy in BFTC905 cells as autophagic inhibitor, 3
      methyladenine, attenuated YM155-induced LC3B-II levels and reversed the
      cytotoxicity of YM155. mTOR inhibitors sirolimus and everolimus did not increase
      YM155-induced expression of LC3B-II nor augment YM155-induced cytotoxicity. These
      results indicate that YM155 exerts its lethal effect on BFTC905 cells via
      apoptotic and autophagic death pathways and suggest that YM155 may be a potential
      drug for the therapy of gemcitabine-resistant bladder cancer.

PMID- 24297646
TI  - Dermatology: future therapeutic perspectives.

PMID- 24297645
TI  - Variability in APOE genotype status in human-derived cell lines: a cause for
      concern in cell culture studies?
AB  - Although cell culture studies have provided landmark discoveries in the basic and
      applied life sciences, it is often under-appreciated that cells grown in culture
      are prone to generating artifacts. Here, we introduce the genotype status
      (exemplified by apolipoprotein E) of human-derived cells as a further important
      parameter that requires attention in cell culture experiments. Epidemiological
      and clinical studies indicate that variations from the main apolipoprotein E3/E3
      genotype might alter the risk of developing chronic diseases, especially
      neurodegeneration, cardiovascular disease, and cancer. Whereas the apolipoprotein
      E allele distribution in human populations is well characterized, the
      apolipoprotein E genotype of human-derived cell lines is only rarely considered
      in interpreting cell culture data. However, we find that primary and immortalized
      human cell lines show substantial variation in their apolipoprotein E genotype
      status. We argue that the apolipoprotein E genotype status and corresponding gene
      expression level of human-derived cell lines should be considered to better avoid
      (or at least account for) inconsistencies in cell culture studies when different
      cell lines of the same tissue or organ are used and before extrapolating cell
      culture data to human physiology in health and disease. 

PMID- 24297647
TI  - Cellulite and focused extracorporeal shockwave therapy for non-invasive body
      contouring: a randomized trial.
AB  - INTRODUCTION: Focused extracorporeal shockwave therapy (ESWT) has been
      demonstrated to improve wound healing and skin regeneration such as in burn
      wounds and scars. We hypothesized that the combination of focused ESWT and a
      daily gluteal muscle strength program is superior to SHAM-ESWT and gluteal muscle
      strength training in moderate to severe cellulite. METHODS: This was a single
      center, double-blinded, randomized-controlled trial. For allocation of
      participants, a 1:1 ratio randomization was performed using opaque envelopes for
      the concealment of allocation. Eligible patients were females aged 18-65 years
      with cellulite. The primary outcome parameter was the photo-numeric Cellulite
      Severity Scale (CSS) determined by two blinded, independent assessors. The
      intervention group (group A) received six sessions of focused ESWT (2,000
      impulses, 0.35 mJ/mm(2), every 1-2 weeks) at both gluteal and thigh regions plus
      specific gluteal strength exercise training. The control group (group B) received
      six sessions of SHAM-ESWT plus specific gluteal strength exercise training.
      RESULTS: The CSS in group A was 10.9 +/- 3.8 (mean +/- SE) before intervention
      and 8.3 +/- 4.1 after 12 weeks (P = 0.001, 2.53 improvement, 95% confidence
      interval (CI) 1.43-3.62). The CSS in group B was 10.0 +/- 3.8 before intervention
      and 10.1 +/- 3.8 after 12 weeks (P = 0.876, 95% CI 1.1-0.97). The change of the
      CSS in group A versus group B was significantly different (P = 0.001, -24.3
      effect size, 95% CI -36.5 to -12.1). CONCLUSION: The combination of non-invasive,
      focused ESWT (0.35 mJ/mm(2), 2,000 impulses, 6 sessions) in combination with
      gluteal strength training was superior to gluteal strength training and SHAM-ESWT
      in moderate to severe cellulite in terms of the CSS in a 3-month perspective.
      Long-term results have to be evaluated in terms of the sustainability of these
      effects.

PMID- 24297649
TI  - Chronic pancreatitis and primary sclerosing cholangitis--first report of
      intrahepatic autologous islet transplantation.
AB  - BACKGROUND: We are reporting first successful intrahepatic autologous islet
      transplantation after total pancreatectomy in a patient with chronic pancreatitis
      and primary sclerosing cholangitis. METHODS: Total pancreatectomy and subsequent
      islet autotransplantation were performed in a 16-year-old boy with intractable
      pain due to chronic pancreatitis in the setting of ulcerative colitis and primary
      sclerosing cholangitis (PSC). Liver biopsy revealed PSC with focal bridging
      fibrosis. The pancreas was surgically removed and digested, and islets were
      isolated, highly purified, and infused intraportally. RESULTS: Over 18-month
      follow-up, the patient did not show progression of chronic liver disease or signs
      of portal hypertension. Magnetic resonance cholangiopancreatography revealed no
      new changes, and liver biopsy did not show progression of the periportal
      fibrosis. Pain medication was weaned over 12 months at which time glycemic
      control was excellent without exogenous insulin supplementation. HbgA1c was 5.9.
      Fifteen months after the procedure, stimulation with a mixed meal led to a
      fourfold increase of serum C-peptide and an eightfold increase of insulin level.
      CONCLUSION: Pancreatic autologous islets can be successfully transplanted into a
      liver affected by PSC without compromising hepatic or graft function. Durability
      of the procedure may be limited in the future by the natural course of the liver
      injury caused by PSC.

PMID- 24297650
TI  - A simple and safe method for Billroth I reconstruction in single-incision
      laparoscopic gastrectomy using a novel intracorporeal triangular anastomotic
      technique.
AB  - The intracorporeal anastomosis is one of the most difficult procedures in single
      incision laparoscopic gastrectomy for gastric cancer. We describe a simple
      technique for intracorporeal triangular Billroth I anastomosis in transumbilical
      single-port surgery. After adequate lymphadenectomy, the stomach and duodenum
      were staple-transected. Small incisions were made to the remnant stomach and the
      duodenum. The anvil of a linear stapler and a staple compartment were inserted
      through the holes, and then both ends were stitched up together by stapler. This
      staple line would be the bottom of the triangular anastomosis. The second and
      third lines were created by closure of the common hole and with simultaneous
      removal of three staple lines (stumps of the stomach and duodenum and the ventral
      side of the first anastomosis) using two linear staplers, respectively,
      completing the triangular anastomosis. We performed this technique in 45 patients
      between March and December 2011. All procedures were completed in single-port
      approaches. There were no postoperative anastomotic complications such as
      anastomotic leak and stricture. The median postoperative hospital stay was 7
      days. Our technique for intracorporeal Billroth I reconstruction is safe and
      feasible. This technique could be a useful surgical option in all laparoscopic
      reconstructive procedures using linear stapling devices.

PMID- 24297651
TI  - Role of primary tumor resection among chemotherapy-treated patients with
      synchronous stage IV colorectal cancer: a survival analysis.
AB  - INTRODUCTION: The benefit of an operation to remove the primary tumor among
      patients with synchronous stage IV colorectal cancer is controversial. This study
      analyzed the survival benefits associated with primary tumor resection among
      chemotherapy-treated stage IV colorectal cancer patients. METHODS: The study
      analyzed 11,716 chemotherapy-treated stage IV colorectal cancer patients in the
      California Cancer Registry between 1996 and 2007, with follow-up through 2009.
      Patients were stratified into operation and non-operation groups. Estimates of
      median overall and colorectal cancer-specific survival were generated. RESULTS:
      Patients undergoing operation compared to those who are not had higher median
      overall and colorectal cancer-specific survival, 21 versus 10 months (p < 0.0001)
      and 22 versus 12 months (p < 0.0001), respectively. Patients who were offered
      surgery but refused had decreased median overall and colorectal cancer-specific
      survival when compared to patients who underwent resection, 8 versus 21 months (p
      < 0.001) and 7 versus 22 months (p < 0.001), respectively. In multivariate
      regression models, patients who underwent resection of primary tumor had improved
      overall (hazard ratio (HR), 0.42; 95% confidence interval (CI) 0.40-0.44, p <
      0.0001) and colorectal cancer-specific survival (HR, 0.43; 95% CI, 0.41-0.45; p <
      0.0001). CONCLUSION: Primary tumor resection is associated with improved survival
      among stage IV chemotherapy-treated colorectal cancer patients.

PMID- 24297652
TI  - Impact of surgeon and hospital volume on mortality, length of stay, and cost of
      pancreaticoduodenectomy.
AB  - BACKGROUND: Improved mortality rates following pancreaticoduodenectomy by high
      volume surgeons and hospitals have been well documented, but less is known about
      the impact of such volumes on length of stay and cost. This study uses data from
      the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample
      (NIS) to examine the effect of surgeon and hospital volume on mortality, length
      of stay, and cost following pancreaticoduodenectomy while controlling for patient
      specific factors. METHODS: Data included 3,137 pancreaticoduodenectomies from the
      NIS performed between 2004 and 2008. Using logistic regression, the relationship
      between surgeon volume, hospital volume, and postoperative mortality, length of
      stay, and cost was estimated while accounting for patient factors. RESULTS: After
      controlling for patient characteristics, patients of high-volume surgeons at high
      volume hospitals had a significantly lower risk of mortality compared to low
      volume surgeons at low-volume hospitals (OR 0.32, p < 0.001). Patients of high
      volume surgeons at high-volume hospitals also had a five day shorter length of
      stay (p < 0.001), as well as significantly lower costs (US$12,275, p < 0.001).
      CONCLUSIONS: The results of this study, which simultaneously accounted for
      surgeon volume, hospital volume, and potential confounding patient
      characteristics, suggest that both surgeon and hospital volume have a significant
      effect on outcomes following pancreaticoduodenectomy, affecting not only
      mortality rates but also lengths of stay and costs.

PMID- 24297653
TI  - Assessment of ISGLS definition of posthepatectomy liver failure and its effect on
      outcome in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Posthepatectomy liver failure (PHLF) is a major complication after
      hepatectomy. As there was no standardized definition, the International Study
      Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized
      ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We
      evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma
      (HCC) patients. METHODS: We retrospectively analyzed 210 consecutive HCC patients
      who underwent curative hepatectomy at our facility from 2005 to 2010. The median
      follow-up period after hepatectomy was 35.2 months. RESULTS: Thirty-nine (18.6%)
      patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at
      1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and
      45.1/57.8%, respectively (P = 0.002). Recurrence-free survival (RFS) rates at 1,
      3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and
      15.7/20.3%, respectively (P = 0.003). Multivariate analysis revealed that PHLF
      was significantly associated with both OS (P = 0.047) and RFS (P = 0.019). Extent
      of resection (P < 0.001), intraoperative blood loss (P = 0.002), and fibrosis
      stage (P = 0.040) were identified as independent risk factors for developing
      PHLF. CONCLUSION: The ISGLS definition of PHLF was associated with OS and RFS in
      HCC patients, and long-term survival will be improved by reducing the incidence
      of PHLF.

PMID- 24297654
TI  - Circular vs. three-quadrant hemorrhoidectomy for end-stage hemorrhoids: short-
      and long-term outcomes of a prospective randomized trial.
AB  - PURPOSE: Circumferential excisional hemorrhoidectomy (CEH) enables the surgeon to
      remove the encircling hemorrhoids completely. The purpose of this study is to
      compare the efficacy of CEH with that of Ferguson hemorrhoidectomy (FH) for end
      stage hemorrhoids. METHODS: Between February 1998 and December 2011, a
      prospective randomized trial was conducted with 688 patients who presented with
      end-stage hemorrhoids and underwent FH or CEH at our center. RESULTS: The patient
      demographics, mean operative times, lengths of hospital stay, and cumulative
      rates of postoperative complications were similar in the study groups.
      Significant differences were revealed in the incidence of postoperative
      hemorrhage (9 vs. 0 patients in the FH and CEH groups, respectively; p = 0.002)
      and in the tendency to form anal stricture (15 vs. 32 patients in the FH and CEH
      groups, respectively; p = 0.02). However, all cases of anal strictures were
      easily managed by digital dilatations. At a mean follow-up of 7.4 (range, 1-14)
      years, accessible patients from the CEH group remained symptom free, whereas 126
      of 308 patients in the FH group indicated that they had recurrent hemorrhoidal
      symptoms. CONCLUSION: Without increasing postoperative complications, CEH
      demonstrates an advantage compared with FH, with regard to reducing the rate of
      recurrence to 0 through complete hemorrhoid removal.

PMID- 24297655
TI  - Circadian disruption and cancer risk: a new concept of stromal niche (review).
AB  - Circadian rhythms regulate a variety of physiological functions. Epidemiological
      evidence indicates that disruption of these circadian rhythms might be linked to
      cancer. In general, imbalances in homeostasis, such as immune and hormonal
      dysfunctions, are thought to be involved in cancer development. The results of a
      recent study suggested that circadian disruption may induce stromal changes
      associated with cancer risk, highlighting the importance of the cancer stem cell
      niche for protecting cancer cells. Current research provides new concepts and
      clarification regarding the function of the tumor niche, and the new concept of a
      stromal niche may help us to understand the additional functions of both cancer
      associated fibroblasts and the extracellular matrix. In this review, we summarize
      our current knowledge regarding the role of circadian rhythms in cancer risk and
      the relevance of the stromal niche in cancer cell survival and progression. 

PMID- 24297657
TI  - Long-term intensive training induced brain structural changes in world class
      gymnasts.
AB  - Many previous studies suggested that both short-term and long-term motor training
      can modulate brain structures. However, little evidence exists for such brain
      anatomical changes in top-level gymnasts. Using diffusion-weighted and structural
      magnetic resonance images of the human brain, we applied voxel-based morphometry
      (VBM) and tract-based spatial statistics (TBSS) as well as FA-VBA (voxel-based
      analysis of fractional anisotropy, a VBM-style analysis) methods to
      quantitatively compare the brain structural differences between the world class
      gymnasts (WCG) and the non-athlete groups. In order to reduce the rate of false
      positive findings, we first determined that the clusters defined at a threshold
      of t > 2.3 and a cluster significance of p < 0.05 (FWE-corrected) across all
      subjects were the brain regions that showed significant differences in a between
      group comparison. We then constructed several between-group comparisons based on
      the repeated diffusion or structural MRI data and created the intersecting
      regions from multiple between-group comparisons. Thus, we found significantly
      decreased fractional anisotropy (FA) not only in the white matter of the WCG in
      areas that included the bilateral superior longitudinal fasciculus, inferior
      longitudinal fasciculus, and inferior occipito-frontal fascicle, but also in the
      gray matter of the WCG in areas that included the bilateral middle cingulum,
      bilateral postcentral gyri, and bilateral motor regions. We also identified
      significantly increased gray matter density in the WCG, especially in the left
      inferior frontal gyrus, bilateral inferior and superior parietal lobule,
      bilateral superior lateral occipital cortex, left cuneus, left angular gyrus, and
      right postcentral gyrus. We speculate that the brain changes of the WCG may
      reflect the gymnasts' extraordinary ability to estimate the direction of their
      movements, their speed of execution, and their identification of their own and
      surrounding objects' locations. Our findings suggest that our method of
      constructing intersecting regions from multiple between-group comparison can
      considerably reduce the false positives, and our results provide new insights
      into the brain structure changes induced by long-term intensive gymnastic
      training. 

PMID- 24297656
TI  - Blue light kills Aggregatibacter actinomycetemcomitans due to its endogenous
      photosensitizers.
AB  - OBJECTIVES: The aim of this study was to demonstrate that the periodontal
      pathogen Aggregatibacter actinomycetemcomitans (AA) can be killed by irradiation
      with blue light derived from a LED light-curing unit due to its endogenous
      photosensitizers. MATERIALS AND METHODS: Planktonic cultures of AA and
      Escherichia coli were irradiated with blue light from a bluephase(r) C8 light
      curing unit with an emission peak at 460 nm, which is usually applied for
      polymerization of dental resins. A CFU-assay was performed for the analysis of
      viable bacteria after treatment. Moreover, bacterial cells were lysed and the
      lysed AA and E. coli were investigated for generation of singlet oxygen.
      Spectroscopic measurements of lysed AA and E. coli were performed and analyzed
      for characteristic absorption and emission peaks. RESULTS: A light dose of 150
      J/cm(2) induced a reduction of >=5 log10 steps of viable AA, whereas no effect of
      blue light was found against E. coli. Spectrally resolved measurements of singlet
      oxygen luminescence showed clearly that a singlet oxygen signal is generated from
      lysed AA upon excitation at 460 nm. Spectroscopic measurements of lysed AA
      exhibited characteristic absorption and emission peaks similar to those of known
      porphyrins and flavins. CONCLUSIONS: AA can be inactivated by irradiation with
      blue light only, without application of an exogenous photosensitizer. CLINICAL
      RELEVANCE: These results encourage further studies on the potential use of these
      blue light-mediated auto-photosensitization processes in the treatment of
      periodontitis for the successful inactivation of Aggregatibacter
      actinomycetemcomitans.

PMID- 24297658
TI  - Dissociation during sex and sexual arousal in women with and without a history of
      childhood sexual abuse.
AB  - Women with a history of childhood sexual abuse (CSA) experience dissociative
      symptoms and sexual difficulties with greater frequency than women without a
      history of CSA. Current models of sexual dysfunction for sexual abuse survivors
      suggest that dissociation may mediate the relationship between CSA and sexual
      arousal difficulties. Dissociation, however, is often conceptualized as a single
      construct in studies of CSA and not as separate domains as in the dissociation
      literature. In the present study, women with (CSA, N = 37) and without (NSA, N =
      22) a history of CSA recruited from the community were asked to indicate the
      frequency and intensity of their experience in two dissociation subgroups,
      derealization and depersonalization, during sex with a partner and in their daily
      life. Findings showed that, in the NSA group, more depersonalization during sex
      with a partner was associated with lower sexual arousal functioning. However, for
      both the NSA and CSA groups, more derealization during sex was associated with
      higher sexual arousal functioning. No measure of dissociation was significantly
      associated with sexual responses in the laboratory. These findings highlight the
      importance of distinguishing between different forms of dissociation (i.e.,
      derealization and depersonalization) in the study of sexual arousal functioning.
      In addition, the findings challenge the notion that dissociation is a main
      predictor of sexual arousal problems in survivors of CSA and suggest that a more
      nuanced relationship may exist.

PMID- 24297659
TI  - Adult attachment among partnered gay men: patterns and associations with sexual
      relationship quality.
AB  - Previous research has found secure adult attachment to be associated positively
      with dimensions of main partner relationship quality and negatively with sexual
      risk taking and sex with casual partners among heterosexuals in primary
      relationships. Potential associations between adult attachment and aspects of
      relationship functioning have received limited attention among gay men. Data were
      collected from both members of 344 gay male couples as part of a community survey
      (M age = 38.6, SD = 9.4). Participants completed a shortened version of the Adult
      Attachment Inventory (Collins & Read, 1990) and the Dyadic Sexual Communication
      Scale (Catania, 1998). They reported the frequency of sex with main partners and
      the number of casual male unprotected sex partners. Data were analyzed using the
      Actor-Partner Interdependence Model. Securely attached individuals reported the
      highest levels of sexual communication and men with securely attached partners
      were the most likely to report having sex with their partners as least once per
      week. Avoidantly attached men reported significantly more casual unprotected anal
      intercourse (UAI) partners compared to other attachment styles. Having an
      avoidantly attached partner was also associated with an increase in the number of
      UAI partners reported. Attachment style is relevant to the sexual relationship
      quality and sexual safety of partnered gay men. Cognitive-interpersonal
      intervention approaches developed to target attachment-related cognitions and
      behaviors may be relevant to HIV prevention efforts in this population. 

PMID- 24297660
TI  - The International Academy of Sex Research: 40 years on.

PMID- 24297661
TI  - Introduction to the special section on sexual health in gay and bisexual male
      couples.

PMID- 24297662
TI  - Inhibition of CD73 stimulates the migration and invasion of B16F10 melanoma cells
      in vitro, but results in impaired angiogenesis and reduced melanoma growth in
      vivo.
AB  - The role of ecto-5'-nucleotidase (CD73), an enzyme providing interstitial
      adenosine, was investigated in B16F10 melanoma progression. Chemical inhibition
      of CD73 decreased adherence of cells to extracellular matrix proteins in vitro
      and led to enhanced migration and invasion. Both processes were reversed by
      adenosine receptor agonists. In CD73-deficient mice, tumor growth was decreased
      in comparison with that of wild-type animals. Additionally, the vasculature of
      CD73-inhibited tumors was impaired and neoangiogenesis in Matrigel plugs was
      reduced. It is, therefore, proposed that although CD73 shows anti-invasive and
      antimigratory function in B16F10 melanoma cells, its proangiogenic action is
      prevalent in vivo and may contribute to increased tumor growth.

PMID- 24297663
TI  - Randomized, double-blind, placebo-controlled, crossover study of the effects of
      lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout
      the day in adults with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Understanding the nature and time course of the pharmacodynamic
      effects of attention-deficit/hyperactivity disorder (ADHD) medications is useful.
      The Cognitive Drug Research Computerized Battery of Tests (CDR-CBT) is a 20-min
      battery of ten standardized, validated neuropsychometric tasks. OBJECTIVE: This
      pilot study examined the sensitivity and responsiveness of the CDR-CBT for
      assessing cognitive function in adults with ADHD prior to and up to 16 h postdose
      during treatment with lisdexamfetamine dimesylate (LDX) or mixed amphetamine
      salts immediate release (MAS-IR; various generics available). METHODS: This was a
      double-blind three-period crossover study. Participants received LDX 50 mg/day,
      MAS-IR 20 mg/day, and placebo (~7 a.m.) for 7 days each in randomized order. CDR
      CBT was administered on day 1 of period 1 and day 7 of each period at scheduled
      times between -0.5 (predose) and 16 h postdose. Composite power of attention
      (PoA) score (sum of simple reaction time, choice reaction time, and digit
      vigilance speed) was the primary outcome measure. The Conners' Adult ADHD Rating
      Scales-Self-Report: Short Version (CAARS-S:S) was administered at baseline and on
      day 1 of period 1, and days 6 and 7 of each treatment period. Tertiary outcomes
      included CDR-CBT composite continuity of attention scores, its component task
      scores, cognitive reaction time, and response variability scores. No inferential
      statistical comparisons were conducted. Safety assessments included adverse
      events (AEs) and vital signs. RESULTS: This analysis included 18 participants
      (mean age 30.8 years); one withdrew because of AEs. Mean pretreatment PoA scores
      were 1175.9-1361.2 ms, scores commensurate with a normative age of >40 years.
      Maximum reductions in PoA scores with LDX and MAS-IR occurred at 5 h postdose at
      day 7 (least squares mean difference [95% CI] of -150.0 [-235.41 to -64.50] and 
      79.8 [-165.72 to 6.21] ms vs. placebo, respectively). CAARS-S:S scores were
      unchanged with LDX and MAS-IR (vs. placebo) at all postdose timepoints. Tertiary
      attention-related CDR-CBT outcomes were sensitive to LDX and MAS-IR (vs.
      placebo). Treatment-emergent AEs and vital signs were consistent with previous
      studies in adult ADHD. CONCLUSION: In adults with ADHD, PoA scores indicated
      impaired attention at baseline and response to treatment with LDX and MAS-IR (vs.
      placebo), demonstrating value for measuring the time course of pharmacologic
      treatment effects.

PMID- 24297664
TI  - Hyperammonemia, resolved by chemotherapy.

PMID- 24297665
TI  - The spirit and the dust.

PMID- 24297666
TI  - Internists' attitudes about assessing and maintaining clinical competence.
AB  - BACKGROUND: Important changes are occurring in how the medical profession
      approaches assessing and maintaining competence. Physician support for such
      changes will be essential for their success. OBJECTIVE: To describe physician
      attitudes towards assessing and maintaining competence. DESIGN: Cross-sectional
      internet survey. PARTICIPANTS: Random sample of 1,000 American College of
      Physicians members who were eligible to participate in the American Board of
      Internal Medicine Maintenance of Certification program. MAIN MEASURES: Questions
      assessed physicians' attitudes and experiences regarding: 1) self-regulation, 2)
      feedback on knowledge and clinical care, 3) demonstrating knowledge and clinical
      competence, 4) frequency of use and effectiveness of methods to assess or improve
      clinical care, and 5) transparency. KEY RESULTS: Surveys were completed by 446 of
      943 eligible respondents (47%). Eighty percent reported it was important
      (somewhat/very) to receive feedback on their knowledge, and 94% considered it
      important (somewhat/very) to get feedback on their quality of care. However, only
      24% reported that they receive useful feedback on their knowledge most/all of the
      time, and 27% reported receiving useful feedback on their clinical care most/all
      of the time. Seventy-five percent agreed that participating in programs to assess
      their knowledge is important to staying up-to-date, yet only 52% reported
      participating in such programs within the last 3 years. The majority (58%)
      believed physicians should be required to demonstrate their knowledge via a
      secure examination every 9-10 years. Support was low for Specialty Certification
      Boards making information about physician competence publically available, with
      respondents expressing concern about patients misinterpreting information about
      their Board Certification activities. CONCLUSIONS: A gap exists between
      physicians' interest in feedback on their competence and existing programs'
      ability to provide such feedback. Educating physicians about the importance of
      regularly assessing their knowledge and quality of care, coupled with enhanced
      systems to provide such feedback, is needed to close this gap.

PMID- 24297667
TI  - Procyanidins from the stem wood of Machilus japonica and their inhibitory effect
      on LDL oxidation.
AB  - The stem wood of Machilus japonica Siebold & Zucc 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, five
      procyanidins, procyanidin A1 (1), procyanidin A2 (2), procyanidin B7 (3),
      cinnamtannin B1 (4), and aesculitannin B (5), were isolated. Their chemical
      structures were identified through spectroscopic data analyses including NMR, MS,
      and IR. This is the first time any of these compounds have been isolated from
      this plant. The compounds were evaluated for inhibition activity on LDL
      oxidation. All of these compounds and the positive control, BHT, showed a very
      high inhibition effect with IC50 values of 0.94, 2.1, 1.8, 1.1, 1.0, and 1.9 MUM,
      respectively.

PMID- 24297669
TI  - Persistent eyelid swelling in a child: lest myiasis be forgot.
AB  - Myiasis involving the eyelid is uncommon. Herein, we present an 8-year-old boy
      who was diagnosed with preseptal cellulitis, yet a single larva was eventually
      extracted from his eyelid. 

PMID- 24297668
TI  - Immune dysregulation in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a common and severe neuro-developmental
      disorder in early childhood which is defined by social and communication deficits
      and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly
      understood. Susceptibility to development of ASD has significant environmental
      components, in addition to the profound genetic heritability. Few genes have been
      associated to the risk for ASD development. There is substantial evidence
      implicating chronic neurological inflammation and immune dysregulation leading to
      upregulation of inflammatory cytokines in the ASD brain, probably due to altered
      blood-brain barrier function. The immune system is characterized by excessive and
      skewed cytokine responses, modulated T cell reactivity, decreased regulation and
      production of immunosuppressive cytokines, modified NK function and increased
      autoantibody production. CONCLUSION: The perinatal environment generates
      vulnerability to chronic neuro-inflammation in the brain associated with profound
      modulation and dysregulation in the immune system leading to the rapid
      development of ASD in genetically susceptible children.

PMID- 24297670
TI  - Incidence of calcaneal apophysitis in the general population.
AB  - BACKGROUND: Calcaneal apophysitis, or Sever's disease, is a traction apophysitis.
      It is a frequent cause of heel pain in children. Knowledge about the exact
      incidence of calcaneal apophysitis in the general population, however, is
      lacking. DESIGN: Cross-sectional study. METHODS: From 34 general practices,
      records of patients between 6 and 17 years old, visiting the general practitioner
      (GP), were analysed. Diagnoses of calcaneal apophysitis were counted using
      computerised registration networks of GPs in 2008, 2009 and 2010. RESULTS: There
      were 16,383 SOAP files searched and a number of 61 children with calcaneal
      apophysitis were established over the years 2010, 2009 and 2008, showing an
      incidence of 3.7 in 1,000 registered patients. CONCLUSION: This is the first
      report on incidence rates of calcaneal apophysitis in general practice. With an
      incidence of 3.7 in 1,000 registered patients, it is a common pathologic entity,
      which requires more research on pathophysiology and therapy. The actual incidence
      may even be higher due the strict inclusion criteria of this study.

PMID- 24297671
TI  - Reference values of perfusion indices in hemodynamically stable newborns during
      the early neonatal period.
AB  - We aimed to determine reference values of perfusion index (PI) in healthy
      newborns during the early neonatal period. Preductal (right hand) and postductal
      (foot) PI values were assessed during the first 5 days of life by using a new
      generation pulse oximetry. A total of 241 newborn infants (196 [81.3 %] term and
      45 [18.7 %] preterm) were enrolled to the study. On the first day, in term
      infants, the median (interquartile range [IQR]) preductal and postductal PI were
      1.35 (1.02-1.91) and 0.88 (0.62-1.22), respectively (p = 0.001). These values
      were 0.88 (0.60-1.26) and 0.61 (0.35-0.92) in preterm infants, with the same
      respect (p = 0.001). From the first to third days, preductal PI remained
      significantly higher than the postductal PI (p < 0.001, for all comparisons).
      Both preductal and postductal PI of term newborns were significantly higher than
      those of preterm infants (p < 0.001, for both comparisons). These differences in
      PI disappeared on the fifth day of life. Conclusion PI values which reflect
      peripheral perfusion seem to reach to a steady state on the fifth day of life
      following physiological maturation. 

PMID- 24297672
TI  - Vasopressin as an adjunct therapy for pulmonary hypertension: a case report.
AB  - Vasopressin is emerging as a therapeutic adjunct option towards treatment of
      shock states in the pediatric population. Its effects on pulmonary vasculature
      are less well understood. This report describes a 5-month-old infant with nitric
      oxide-unresponsive pulmonary hypertension, oxygenation failure, and systemic
      hypotension. Vasopressin therapy improved oxygenation and blood pressure and
      biventricular function, allowing weaning of nitric oxide and inotropic support.
      No decrease in coronary flow was noted. CONCLUSIONS: Vasopressin could be
      considered as an adjunct option in infants with pulmonary hypertension and
      systemic hypotension. Echocardiographic monitoring during treatment is
      recommended.

PMID- 24297673
TI  - The religious-spiritual self-image and behaviours among adolescent street
      children in Harare, Zimbabwe.
AB  - The present study sought to explore the relationship between street childhood and
      adolescent religious-spiritual self-image. In Zimbabwe, there has been a rise in
      street children population in the urban centres. The current study investigated
      whether adolescent street children live and work in an eco-developmentally risky
      context for the development of positive religious-spiritual self-image. This rise
      in street children population has been in the context of a socio-politico
      economic crisis, which was marked by record inflation rates and the HIV and AIDS
      pandemic. The research objectives were to investigate the nature of religious
      spiritual self-image for street-living adolescent children, and to determine the
      effects of self-image on the behaviour of street-living adolescent children. A
      psycho-ethnographic research design was employed in this study. This involved
      collection of data for a sustained period in the context within which the
      participants live. The participants were 16 street-living adolescent children
      aged between 12 and 18 years and six key informants all in Harare in Zimbabwe. A
      total of 22 participants took part in this study. Snowballing was used to recruit
      key informant interviewees, while purposive sampling was used to recruit
      participants for focus group discussions, in-depth interview, and participant and
      non-participant observations. Key informant interviews, focus group discussions,
      in-depth interviews, and participant and non-participant observations were the
      data collection methods. Thematic content analysis was used for analysing the
      data. This thematic content analytic method helped to identify themes on the
      religious-spiritual self-image that emerged from the data. Data analysis revealed
      that the adolescent street children's religious-spiritual self-image is largely
      negative. Most street-living adolescent children believed that they were
      controlled and influenced by evil spirits and that their relatives were casting
      bad spells on them. The negative religious-spiritual self-image among the street
      children had important negative implications on psychological functioning, moral
      behaviours, and social relations for the street-living children.

PMID- 24297674
TI  - Spirit or Fleeting Apparition? Why Spirituality's Link with Social Support Might
      Be Incrementally Invalid.
AB  - Previously published path models apparently confirm the belief-as-benefit
      perspective that spirituality boosts well-being via social support. The broad
      acceptance of such findings has motivated recommendations that clinical
      psychologists and psychiatrists routinely assess their patients' spiritual
      status. Skeptics retort that past findings are statistically confounded and that
      numinous beliefs and well-being are unrelated. A multivariate regression analysis
      testing whether spirituality explains variance in social support after
      personality traits are simultaneously included is reported. Although spirituality
      displays a significant positive correlation and partial correlation (after
      controlling for socio-demographics) with social support, regression analysis
      specifying agreeableness and conscientiousness-individual differences related to
      both spirituality and social support-as predictors renders spirituality
      nonsignificant. In summary, spirituality's correlation with social support
      appears spurious; demonstrating the hazards of relying on simple associations and
      highlighting the urgent need for researchers to utilize statistical methods
      capable of establishing cause and parsing effects across rival theoretical
      explanations.

PMID- 24297676
TI  - Brain imaging: closing the gap between basic research and clinical application is
      urgently needed.

PMID- 24297675
TI  - Resting state FMRI research in child psychiatric disorders.
AB  - Concurring with the shift from linking functions to specific brain areas towards
      studying network integration, resting state FMRI (R-FMRI) has become an important
      tool for delineating the functional network architecture of the brain. Fueled by
      straightforward data collection, R-FMRI analysis methods as well as studies
      reporting on R-FMRI have flourished, and already impact research on child- and
      adolescent psychiatric disorders. Here, we review R-FMRI analysis techniques and
      outline current methodological debates. Furthermore, we provide an overview of
      the main R-FMRI findings related to child- and adolescent psychiatric disorders.
      R-FMRI research has contributed significantly to our understanding of brain
      function in child and adolescent psychiatry: existing hypotheses based on task
      based FMRI were confirmed and new insights into the brain's functional
      architecture of disorders were established. However, results were not always
      consistent. While resting state networks are robust and reproducible,
      neuroimaging research in psychiatric disorders is especially complicated by
      tremendous phenotypic heterogeneity. It is imperative that we overcome this
      heterogeneity when integrating neuroimaging into the diagnostic and treatment
      process. As R-FMRI allows investigating the richness of the human functional
      connectome and can be easily collected and aggregated into large-scale datasets,
      it is clear that R-FMRI can be a powerful tool in our quest to understand
      psychiatric pathology. 

PMID- 24297677
TI  - Cell line modeling for systems medicine in cancers (review).
AB  - Unexpected drug efficacy or resistance is poorly understood in cancers because of
      the lack of systematic analyses of drug response profiles in cancer tissues of
      various genotypic backgrounds. The recent development of high-throughput
      technologies has allowed massive screening of chemicals and drugs against panels
      of heterogeneous cancer cell lines. In parallel, multi-level omics datasets,
      including genome-wide genetic alterations, gene expression and protein
      regulation, have been generated from diverse sets of cancer cell lines, thus
      providing a surrogate system, known as cancer cell line modeling, that can
      represent cancer diversity. Taken together, recent efforts with cancer cell line
      modeling have enabled a systematic understanding of the causal factors of varied
      drug responses in cancers. These large-scale association studies could
      potentially predict and optimize target windows for drug treatment in cancer
      patients. The present review provides an overview of the major types of cell line
      based large datasets and their applications in cancer studies. Moreover, this
      review discusses recent integrated approaches that use multi-level datasets to
      discover synergistic drug combination or repositioning for cancer treatment. 

PMID- 24297678
TI  - The Canadian critical care nutrition guidelines in 2013: an update on current
      recommendations and implementation strategies.
AB  - Clinical practice guidelines (CPGs) are systematically developed statements to
      assist practitioners and patient decisions about appropriate healthcare for
      specific clinical circumstances, and are designed to minimize practice variation,
      improve costs, and improve clinical outcomes. The Canadian Critical Care Practice
      Guidelines (CCPGs) were first published in 2003 and most recently updated in
      2013. A total of 68 new randomized controlled trials were identified since the
      last version in 2009, 50 of them published between 2009 and 2013. The remaining
      articles were trials published before 2009 but were not identified in previous
      iterations of the CCPGs. For clinical practice guidelines to be useful to
      practitioners, they need to be up-to-date and be reflective of the current body
      of evidence. Herein we describe the process by which the CCPGs were updated. This
      process resulted in 10 new sections or clinical topics. Of the old clinical
      topics, 3 recommendations were upgraded, 4 were downgraded, and 27 remained the
      same. To influence decision making at the bedside, these updated guidelines need
      to be accompanied by active guideline implementation strategies. Optimal
      implementation strategies should be guided by local contextual factors including
      barriers and facilitators to best practice recommendations. Moreover, evaluating
      and monitoring performance, such as participating in the International Nutrition
      Survey of practice, should be part of any intensive care unit's performance
      improvement strategy. The active implementation of the updated CCPGs may lead to
      better nutrition care and improved patient outcomes in the critical care setting.

PMID- 24297679
TI  - Need for a biomarker to de-escalate antimicrobial empirical therapy.

PMID- 24297680
TI  - Influence of gestational age and body weight on the pharmacokinetics of labetalol
      in pregnancy.
AB  - BACKGROUND AND OBJECTIVES: Labetalol is frequently prescribed for the treatment
      of hypertension during pregnancy; however, the influence of pregnancy on
      labetalol pharmacokinetics is uncertain, with inconsistent findings reported by
      previous studies. This study examined the population pharmacokinetics of oral
      labetalol during and after pregnancy in women receiving labetalol for
      hypertension. METHODS: Data were collected from 57 women receiving the drug for
      hypertension from the 12th week of pregnancy through 12 weeks postpartum using a
      prospective, longitudinal design. A sparse sampling strategy guided collection of
      plasma samples. Samples were assayed for labetalol by high-performance liquid
      chromatography. Estimation of population pharmacokinetic parameters and covariate
      effects was performed by nonlinear mixed effects modeling using NONMEM. The final
      population model was validated by bootstrap analysis and visual predictive check.
      Simulations were performed with the final model to evaluate the appropriate body
      weight to guide labetalol dosing. RESULTS: Lean body weight (LBW) and gestational
      age, i.e. weeks of pregnancy, were identified as significantly influencing oral
      clearance (CL/F) of labetalol, with CL/F ranging from 1.4-fold greater than
      postpartum values at 12 weeks' gestational age to 1.6-fold greater at 40 weeks.
      Doses adjusted for LBW provide more consistent drug exposure than doses adjusted
      for total body weight. The apparent volumes of distribution for the central
      compartment and at steady-state were 1.9-fold higher during pregnancy.
      CONCLUSIONS: Gestational age and LBW impact the pharmacokinetics of labetalol
      during pregnancy and have clinical implications for adjusting labetalol doses in
      these women.

PMID- 24297681
TI  - Expression of early growth response-1 in colorectal cancer and its relation to
      tumor cell proliferation and apoptosis.
AB  - Early growth response-1 (Egr-1) is implicated in the regulation of cell growth,
      proliferation, differentiation and apoptosis. Egr-1 is considered tobe either a
      tumor-suppressor or tumor-promoter, depending on the cell type and environment.
      The aim of the present study was to evaluate the expression of Egr-1 in
      colorectal cancer and its correlation with tumor cell proliferation, apoptosis
      and clinicopathological features. The expression of Egr-1 in colorectal cancer
      tissues was investigated by reverse transcription-polymerase chain reaction (RT
      PCR), western blotting and immunohistochemistry. Apoptosis was detected by
      terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate
      (dUTP) nick end labeling (TUNEL), and cellular proliferative activity was
      evaluated by immunohistochemical staining with the Ki-67 antibody. Egr-1
      expression was significantly elevated in colorectal cancer tissues, when compared
      to that in the paired normal mucosa at the mRNA and protein levels. In addition,
      Egr-1 expression was significantly increased in the metastatic lymph node
      tissues, when compared to that in the non-metastatic lymph node tissues at the
      protein level. The mean Ki-67 labeling index (KI) and apoptotic index (AI) values
      for 158 tumors were 53.6+/-15.4 and 9.0+/-1.0, respectively. Higher KI values
      were significantly associated with distant metastasis. Lower AI values were
      significantly associated with lymph node metastasis. However, KI or AI values
      were not associated with patient survival. The mean KI value of Egr-1-positive
      tumors was significantly higher than that of Egr-1-negative tumors. However,
      there was no significant difference between Egr-1 expression and AI value.
      Positive expression of Egr-1 was significantly associated with age,
      lymphovascular invasion, lymph node and distant metastasis, tumor stage and poor
      survival. These results indicate that Egr-1 may be associated with colorectal
      cancer progression via tumor cell proliferation.

PMID- 24297682
TI  - First-in-human phase II trial of the botanical formulation PHY906 with
      capecitabine as second-line therapy in patients with advanced pancreatic cancer.
AB  - BACKGROUND: Preclinical studies showed a Chinese botanical formula, PHY906, has
      synergistic anti-tumor activity with capecitabine. Our phase I study determined
      maximal tolerated dose of capecitabine 1,500 mg/m(2) BID day 1-7 and PHY906 800
      mg BID day 1-4 every 2 weeks. We conducted this phase II study to explore the
      efficacy of capecitabine and PHY906 in patients with advanced pancreatic cancer
      who were previously treated with gemcitabine-based regimens. METHODS: Patients
      with pancreatic cancer and an Eastern Cooperative Oncology Group performance
      status of 0-2 received PHY906 and capecitabine. Toxicity was assessed per NCI
      CTCAE v3.0 and response per response evaluation criteria in solid tumors q 6
      weeks. Correlative studies of cytokines, chemokines and growth factors were
      tested using a cytometric bead array. Quality of life was assessed by utilizing
      Edmonton symptom assessment system. The primary objective was overall survival.
      RESULTS: The study enrolled 25 patients. Median progression-free survival (mPFS)
      was 10.1 weeks (range 0.4-54.1) and median overall survival (mOS) was 21.6 weeks
      (range 0.4-84.1). Eighteen patients received at least 2 cycles, and achieved mPFS
      of 12.3 weeks and mOS of 28 weeks. Six-month survival rate was 44 % (11/25).
      Unsupervised clustering of patients grouped those with shortened survival
      together by their cytokine profile showed that only IL-6 had a significant
      difference (p < .001) between short- and long-term survivors. CONCLUSIONS:
      Capecitabine plus PHY906 provides a safe and feasible salvage therapy after
      gemcitabine failure for APC. Role of IL-6 in tumor progression and tumor cachexia
      needs to be investigated with respect to its relation to pathophysiology of
      pancreatic cancer and development of anti-IL-6 therapeutics.

PMID- 24297683
TI  - A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi)
      PNT2258 in patients with advanced solid tumors.
AB  - PURPOSE: Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics
      were assessed in this phase 1 study of PNT2258, a BCL-2-targeted liposomal
      formulation of a 24-base DNA oligonucleotide called PNT100. METHODS: Patients
      with malignant solid tumors were assigned sequentially to one of ten dose
      escalation cohorts of PNT2258 at 1, 2, 4, 8, 16, 32, 64, 85, 113, and 150 mg/m(2)
      administered intravenously on days 1 through 5 of each 21-day cycle.
      Pharmacokinetics were determined on days 1 and 5 of the first cycle. Lymphocyte
      and platelets concentrations were measured for evidence of BCL2-targeted effect.
      CT scans were used to identify radiologic evidence of anti-tumor effect. RESULTS:
      Twenty-two subjects received PNT2258, and the maximum tolerated dose for PNT2258
      was not reached. Doses at or above 32 mg/m(2) resulted in exposure to PNT2258
      above the exposure level required for anti-tumor activity in preclinical
      xenograft testing of 22,377 ng h/ml (PK analysis 2012). Fatigue was the most
      commonly reported adverse event. Dose-limiting toxicity, manifesting as a
      transient increase in aspartate aminotransferase, occurred at 150 mg/m(2), the
      highest dose tested. Four subjects, two each with diagnosis of non-small-cell
      lung cancer and sarcoma, treated at doses of 64 mg/m(2) or higher, remained on
      study for 5-8 cycles. CONCLUSIONS: PNT2258 was safe and well tolerated at the
      doses tested up to 150 mg/m(2). Exposure to PNT2258 resulted in clinically
      manageable decreases in lymphocyte and platelet concentrations.

PMID- 24297685
TI  - Detection of a novel mutation in exon 20 of the BRCA1 gene.
AB  - Hereditary breast cancer constitutes 5-10% of all breast cancer cases. Inherited
      mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority
      of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a
      functional duplicated globular domain, which helps with DNA damage repair and
      cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense
      variants with structural and functional effects have been documented within the
      BRCT domain. Interpreting the results of mutation screening of tumor-suppressor
      genes that can have high-risk susceptibility mutations is increasingly important
      in clinical practice. This study includes a novel mutation, p.His1746 Pro
      (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In
      silico analysis suggests that this mutation could alter the stability and
      orientation of the BRCT domain and the differential binding of the BACH1
      substrate. 

PMID- 24297684
TI  - The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from
      various levels of the respiratory tract.
AB  - Airway epithelium acts as multifunctional site of response in the respiratory
      tract. Epithelial activity plays an important part in the pathophysiology of
      obstructive lung disease. In this study, we compare normal human epithelial cells
      from various levels of the respiratory tract in terms of their reactivity to pro
      allergic and pro-inflammatory stimulation. Normal human nasal, bronchial and
      small airway epithelial cells were stimulated with IL-4 and IL-13. The
      expressions of the eotaxins IL-6 and CXCL8 were evaluated at the mRNA and protein
      levels. The effects of pre-treatment with IFN-gamma on the cell reactivity were
      measured, and the responses to TNF-alpha, LPS and IFN-gamma were evaluated. All
      of the studied primary cells expressed CCL26, IL-6 and IL-8 after IL-4 or IL-13
      stimulation. IFN-gamma pre-treatment resulted in decreased CCL26 and increased IL
      6 expression in the nasal and small airway cells, but this effect was not
      observed in the bronchial cells. IL-6 and CXCL8 were produced in varying degrees
      by all of the epithelial primary cells in cultures stimulated with TNF-alpha, LPS
      or IFN-gamma. We showed that epithelial cells from the various levels of the
      respiratory tract act in a united way, responding in a similar manner to
      stimulation with IL-4 and IL-13, showing similar reactivity to TNF-alpha and LPS,
      and giving an almost unified response to IFN-gamma pre-stimulation. 

PMID- 24297686
TI  - Yeast ABC proteins involved in multidrug resistance.
AB  - Pleiotropic drug resistance is a complex phenomenon that involves many proteins
      that together create a network. One of the common mechanisms of multidrug
      resistance in eukaryotic cells is the active efflux of a broad range of
      xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces
      cerevisiae is often used as a model to study such activity because of the
      functional and structural similarities of its ABC transporters to mammalian ones.
      Numerous ABC transporters are found in humans and some are associated with the
      resistance of tumors to chemotherapeutics. Efflux pump modulators that change the
      activity of ABC proteins are the most promising candidate drugs to overcome such
      resistance. These modulators can be chemically synthesized or isolated from
      natural sources (e.g., plant alkaloids) and might also be used in the treatment
      of fungal infections. There are several generations of synthetic modulators that
      differ in specificity, toxicity and effectiveness, and are often used for other
      clinical effects.

PMID- 24297687
TI  - Incidence, determinants, and prognostic significance of hyperkalemia and
      worsening renal function in patients with heart failure receiving the
      mineralocorticoid receptor antagonist eplerenone or placebo in addition to
      optimal medical therapy: results from the Eplerenone in Mild Patients
      Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).
AB  - BACKGROUND: Mineralocorticoid receptor antagonists improve outcomes in patients
      with systolic heart failure but may induce worsening of renal function (WRF) and
      hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor
      antagonist-related WRF and for HK, as well as the association between HK and WRF
      with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and
      Survival Study in Heart Failure (EMPHASIS-HF). METHODS AND RESULTS: Serial
      changes in estimated glomerular filtration rate and in serum potassium were
      available in 2737 patients during a median 21-month follow-up. HK variably
      defined as serum K>4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9%
      patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in
      estimated glomerular filtration rate>20% or >30% from baseline occurred in 27%
      and 14% of patients, respectively. Patients assigned eplerenone displayed modest
      and early but significant and persistent (1) rise in serum potassium and (2)
      reduction in estimated glomerular filtration rate when compared with those
      assigned placebo. In multivariate analyses, eplerenone was associated with a
      higher incidence of WRF and HK, which were interrelated and also associated with
      baseline patient characteristics (eg, age>=75 years, hypertension, diabetes
      mellitus, nonwhite race, ejection fraction<30%, and treatment with an
      antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits
      without any significant interaction with the association between HK>5.5 mmol/L
      only and WRF and worse outcomes. CONCLUSIONS: In patients with heart failure
      receiving optimal therapy, WRF and HK were more frequent when eplerenone was
      added, but their occurrence did not eliminate the survival benefit of eplerenone.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00232180.

PMID- 24297688
TI  - Increased sarcolipin expression and adrenergic drive in humans with preserved
      left ventricular ejection fraction and chronic isolated mitral regurgitation.
AB  - BACKGROUND: There is currently no therapy proven to attenuate left ventricular
      (LV) dilatation and dysfunction in volume overload induced by isolated mitral
      regurgitation (MR). To better understand molecular signatures underlying isolated
      MR, we performed LV gene expression analyses and overlaid regulated genes into
      ingenuity pathway analysis in patients with isolated MR. METHODS AND RESULTS:
      Gene arrays from LV tissue of 35 patients, taken at the time of surgical repair
      for isolated MR, were compared with 13 normal controls. Cine-MRI was performed in
      31 patients before surgery to measure LV function and volume from serial short
      axis summation. LV end-diastolic volume was 2-fold (P=0.005) higher in MR
      patients than in normal controls, and LV ejection fraction was 64+/-7% (50%-79%)
      in MR patients. Ingenuity pathway analysis identified significant activation of
      pathways involved in beta-adrenergic, cAMP, and G-protein-coupled signaling,
      whereas there was downregulation of pathways associated with complement
      activation and acute phase response. SERCA2a and phospholamban protein were
      unchanged in MR versus control left ventricles. However, mRNA and protein levels
      of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) regulatory protein sarcolipin,
      which is predominantly expressed in normal atria, were increased 12- and 6-fold,
      respectively. Immunofluorescence analysis confirmed the absence of sarcolipin in
      normal left ventricles and its marked upregulation in MR left ventricles.
      CONCLUSIONS: These results demonstrate alterations in multiple pathways
      associated with beta-adrenergic signaling and sarcolipin in the left ventricles
      of patients with isolated MR and LV ejection fraction>50%, suggesting a
      beneficial role for beta-adrenergic blockade in isolated MR.

PMID- 24297689
TI  - High prevalence of occult pulmonary venous hypertension revealed by fluid
      challenge in pulmonary hypertension.
AB  - BACKGROUND: Determining the cause for pulmonary hypertension is difficult in many
      patients. Pulmonary arterial hypertension (PAH) is differentiated from pulmonary
      venous hypertension (PVH) by a wedge pressure (PWP)>15 mm Hg in PVH. Patients
      undergoing right heart catheterization for evaluation of pulmonary hypertension
      may be dehydrated and have reduced intravascular volume, potentially leading to a
      falsely low measurement of PWP and an erroneous diagnosis of PAH. We hypothesized
      that a fluid challenge during right heart catheterization would identify occult
      pulmonary venous hypertension (OPVH). METHODS AND RESULTS: We reviewed the
      results of patients undergoing fluid challenge in our pulmonary hypertension
      database from 2004 to 2011. Baseline hemodynamics were obtained and repeated
      after infusion of 0.5 L of normal saline for 5 to 10 minutes. Patients were
      categorized as OPVH if PWP increased to >15 mm Hg after fluid challenge. Baseline
      hemodynamics in 207 patients met criteria for PAH. After fluid challenge, 46
      patients (22.2%) developed a PWP>15 mm Hg and were reclassified as OPVH. Patients
      with OPVH had a greater increase in PWP compared with patients with PAH, P<0.001,
      and their demographics and comorbid illnesses were similar to patients with PVH.
      There were no adverse events related to fluid challenge. CONCLUSIONS: Fluid
      challenge at the time of right heart catheterization is easily performed, safe,
      and identifies a large group of patients diagnosed initially with PAH, but for
      whom OPVH contributes to pulmonary hypertension. These results have implications
      for therapeutic trials in PAH and support the routine use of fluid challenge
      during right heart catheterization in patients with risk factors for PVH.

PMID- 24297690
TI  - Association of heart rate at hospital discharge with mortality and
      hospitalizations in patients with heart failure.
AB  - BACKGROUND: Heart failure (HF) is associated with a high burden of morbidity and
      mortality. Hospital discharge is an opportunity for identification of modifiable
      prognostic factors in the transition to chronic HF. METHODS AND RESULTS: We
      examined the association of discharge heart rate with 30-day and 1-year mortality
      and hospitalization outcomes in a cohort of 9097 patients with HF discharged from
      hospital. Discharge heart rate was categorized into predefined groups: 40 to 60
      (n=1333), 61 to 70 (n=2170), 71 to 80 (n=2631), 81 to 90 (n=1700), and >90 bpm
      (n=1263). There was a significant increase in all-cause 30-day mortality with
      adjusted odds ratios of 1.59 (95% confidence interval [CI], 1.18-2.14; P=0.003)
      for discharge heart rates 81 to 90 bpm and 1.56 (95% CI, 1.13-2.16; P=0.007) for
      heart rates>90 bpm when compared with the reference group (heart rates, 61-70
      bpm). Cardiovascular death risk at 30 days was also higher with adjusted odds
      ratio 1.59 (discharge heart rates, 81-90 bpm; 95% CI, 1.09-2.33; P=0.017) and
      1.65 (discharge heart rates, >90 bpm; 95% CI, 1.09-2.48; P=0.017). One-year all
      cause mortality (adjusted odds ratio, 1.41; 95% CI, 1.16-1.72; P<0.001) and
      cardiovascular death (adjusted odds ratio, 1.47; 95% CI, 1.12-1.92; P=0.005) were
      higher with discharge heart rates>90 bpm when compared with the reference group
      (heart rates, 40-60 bpm). Readmissions for HF (adjusted hazard ratio, 1.26; 95%
      CI, 1.04-1.54; P=0.021) and cardiovascular disease (adjusted hazard ratio, 1.29;
      95% CI, 1.08-1.54; P=0.004) within 30 days were also higher with discharge heart
      rates>90 bpm. CONCLUSIONS: Higher discharge heart rates were associated with
      greater risk of all-cause and cardiovascular mortality<=1-year follow-up and an
      elevated risk of 30-day readmission for HF and cardiovascular disease.

PMID- 24297691
TI  - The outcome of paediatric LCP hip plate use in children with and without
      neuromuscular disease.
AB  - BACKGROUND: The relatively new paediatric LCP hip plate (Synthes GmBH
      Eimattstrasse 3 CH-4436 Oberdorff) is used in children, both with and without
      neuromuscular disease, for fixation of proximal femoral osteotomy for a variety
      of indications. MATERIALS AND METHODS: We retrospectively reviewed the notes and
      radiographs of all those children who have had paediatric LCP device for the
      fixation of proximal femoral osteotomy and proximal femur fractures in our
      institution (Royal Manchester Children's Hospital), between October 2007 and July
      2010, for their clinical progress, mobilization status, radiological healing and
      any complications. RESULTS: Forty-three paediatric LCP hip plates were used in 40
      patients (27 males and 13 females) for the fixation of 40 proximal femoral
      osteotomies and three proximal femur fractures. This included 13 children with
      underlying neuromuscular pathology and 27 children without neuromuscular disease.
      All osteotomies and fractures radiologically healed within 6 months [majority (n
      = 40) within 3 months]. There was no statistically significant difference (p =
      0.45) in the neck shaft angle between the immediately post-operative and final X
      rays after completion of bone healing. There were no implant-related
      complications both in patients with and without neuromuscular disease. No
      metalwork loosening was observed and no plate revisions were required. Three post
      operative fractures occurred in patients with neuromuscular pathology treated
      with post-operative plaster immobilisation. CONCLUSION: The paediatric LCP hip
      plate provides a stable and reliable fixation of the proximal femoral osteotomy
      performed for a variety of paediatric orthopaedic conditions.

PMID- 24297692
TI  - Parasitism of Argulus japonicus in cultured and wild fish of Guangdong, China
      with new record of three hosts.
AB  - This study aimed to demonstrate the ability of Argulus japonicus to infect a wide
      range of freshwater fishes, as well as to understand the effects of fish origin
      and host body size on the incidence of A. japonicus. Samples of cultured and wild
      fish were collected randomly from July 2010 to March 2013, using angling, long
      lining, gill-netting, and trapping from rivers and fish farms in Guangdong
      province, South China. Eight fish species were found to be heavily infected
      including the common carp, the goldfish, the black carp, the silver carp, the
      brown trout, the rainbow trout, the mandarin fish, and the perch. Furthermore,
      the black carp, the brown trout, and the mandarin fish were recorded as new hosts
      for the first time. During the present study, a total of 2,271 fishes were
      examined, out of which 712 fishes were found to be infected by a total of 1,443
      A. japonicus. Abundance and intensity of A. japonicus infection were
      significantly influenced by origin of fishes (cultured and wild) and total length
      (class I, <250 mm; class II, 250-350 mm; and class III, >350 mm) of fish species,
      whereas varied impacts on prevalence of infection were observed. The correlation
      between total length of fishes and prevalence of A. japonicus infection was
      variable, where no significant correlation was observed in the black carp, the
      silver carp, the mandarin fish, and the perch. In spite of the weak negative
      correlation between body size of the silver carp and prevalence of infection, A.
      japonicus was the most abundant and intensive in the silver carp. Thus,
      aquaculturists should pay particular attention to the control of these fish lice
      due to its host biodiversity.

PMID- 24297693
TI  - Muscular sarcocystosis in two arctic foxes (Vulpes lagopus) due to Sarcocystis
      arctica n. sp.: sarcocyst morphology, molecular characteristics and phylogeny.
AB  - The arctic fox (Vulpes lagopus) is a critically endangered species in Norway, and
      therefore, the small population is closely monitored, and most foxes found dead
      are subjected to necropsy. In two deceased foxes, thin-walled muscular sarcocysts
      were first detected in histological sections, and numerous sarcocysts were later
      found in frozen and thawed muscle samples from Fox 1. These sarcocysts measured 1
      12 * 0.1-0.25 mm and had closely spaced, short, knob-like protrusions, giving the
      cysts a serrated outline. Genomic DNA was extracted from eight isolated
      sarcocysts (Fox 1) and two muscle samples (Fox 2) and subjected to polymerase
      chain reaction amplification at four loci: the nuclear 18S and 28S ribosomal RNA
      genes and internal transcribed spacer 1 region and the mitochondrial cytochrome c
      oxidase subunit 1 gene (cox1). Both foxes were infected by the same Sarcocystis
      sp., which displayed little or no genetic variation at the three nuclear loci
      (99.9-100% identity) and slightly more variation at cox1 (99.4-100% identity).
      Sequence comparisons and phylogenetic analyses revealed that this species was
      distinct from other named Sarcocystis spp. but was closely related to various
      species using avian intermediate hosts and possibly identical to an unnamed
      species reported from two American dogs. The species described from the two
      arctic foxes was named Sarcocystis arctica n. sp.

PMID- 24297694
TI  - Extrinsic- and intrinsic-dependent variation in component communities and
      patterns of aggregations in helminth parasites of great cormorant (Phalacrocorax
      carbo) from N.E. Poland.
AB  - In the present study, we investigate the effect extrinsic (habitat and season)
      and intrinsic (host's age and sex) factors on the richness, diversity, and
      structure of parasite component communities and aggregation patterns in the
      helminth fauna of the great cormorant Phalacrocorax carbo from northeastern
      Poland. The helminth fauna of cormorants from the brackish water habitat was far
      richer (30 species) than in those from freshwater lakes (18 species) and strongly
      depend on season and age of the host. The values of diversity index strongly
      varied in relation to habitat and host age with clear seasonal differences in the
      value of diversity index, i.e., its value increased over time in adults from the
      brackish water habitat and decreased in those from the freshwater lakes. The
      number of helminths in adult and immature birds varied, depending on the season
      and habitat: in the brackish water habitat, the overall percentage of helminths
      was higher in spring than in summer, while in the freshwater habitat a higher
      proportion of helminths was recorded in summer. During spring, in the brackish
      water habitat, we observed a higher level of aggregation (for all groups of
      helminths) than in autumn. The opposite pattern was found in the freshwater
      habitat. However, this regularity was typical of adult birds only. In immature
      hosts, the level of aggregation was not predictable and varied among the higher
      taxa. Our study clearly showed that processes determinate diversity, structure,
      richness, and patterns of aggregation in helminth assemblages of avian hosts are
      multi-origin and highly complex. 

PMID- 24297695
TI  - Transcriptome profilings of female Schistosoma japonicum reveal significant
      differential expression of genes after pairing.
AB  - Pairing of Schistosoma japonicum initiates female development, leads to female
      sexual maturation, and maintains this mature state. To understand the mechanism
      involved in these processes, we studied parasites isolated from single- and
      double-sex cercariae-infected mice using deep-sequencing analysis, Solexa, to
      uncover pair-regulated transcriptional profiles. In this study, we report the
      results of high-throughput tag-sequencing (Tag-seq) analysis of the transcriptome
      of female worms 18 and 23 days postsingle- and double-sex infections. We
      sequenced over 3 million tags, obtained a total of 14,034, 27,251, 22,755, and
      22,555 distinct tags corresponding to 5,773, 9,794, 8,885, and 8,870 tag-mapped
      genes for 23-day-old female schistosomula from double-sex infections (23DSI), 23
      day-old female schistosomula from single-sex infections (23SSI), 18-day-old
      female schistosomula from double-sex infections (18DSI), and 18-day-old female
      schistosomula from single-sex infections (18SSI), respectively. Analyses of
      differentially expressed genes revealed similarities in the gene expression
      profiles between 18SSI and 18DSI as well as rational differential gene expression
      between 18SSI and 23SSI. However, fewer upregulated genes were found in 23DSI
      compared with 18DSI. Of the 3,446 differentially expressed genes between 23DSI
      and 23SSI, 2,913 genes were upregulated in 23SSI, whereas only 533 genes were
      upregulated in 23DSI. In these upregulated genes in 23DSI, phosphoglycerate
      mutase, superoxide dismutase, egg antigen, ribosomal proteins, ferritin-1 heavy
      chain, and eukaryotic translation initiation factor 2 were detected. Detection of
      these genes suggests that gene expression in 23DSI is specialized for functions
      such as promotion and maintenance of female sexual maturation and egg production.
      Quantitative real-time (RT)-PCR analysis confirmed the Solexa results, thereby
      supporting the reliability of the system. Our results offer new insights into the
      biological significance of pairing, which directs the expression of genes
      specific for sexual maturation and egg production.

PMID- 24297696
TI  - NIH research funding and early career physician scientists: continuing challenges
      in the 21st century.
AB  - Physician scientists (researchers with either M.D. or M.D.-Ph.D. degrees) have
      the unique potential to combine clinical perspectives with scientific insight,
      and their participation in biomedical research has long been an important topic
      for policymakers and educators. Given the recent changes in the research
      environment, an update and extension of earlier studies of this population was
      needed. Our findings show that physician scientists are less likely to take a
      major role in biomedical research than they were in the past. The number of
      physician scientists receiving postdoctoral research training and career
      development awards is at an all-time low. Physician scientists today, on average,
      receive their first major research award (R01 equivalent) at a later age than in
      the 1980s. The number of first-time R01-equivalent awards to physicians is at the
      same level as it was 30 yr ago, but physicians now represent a smaller percentage
      of the grant recipients. The long-term decline in the number of physicians
      entering research careers was temporarily halted during the period of substantial
      U.S. National Institutes of Health (NIH) budget growth (1998-2003). These gains
      are lost, however, in the subsequent years when NIH budgets failed to keep pace
      with rising costs.

PMID- 24297697
TI  - A dynamin-related protein contributes to Trichomonas vaginalis hydrogenosomal
      fission.
AB  - Trichomonas vaginalis is a highly divergent, unicellular eukaryote of the phylum
      Metamonada, class Parabasalia, and the source of a common sexually transmitted
      infection. This parasite lacks mitochondria, but harbors an evolutionarily
      related organelle, the hydrogenosome. We explored the role of dynamin-related
      proteins (DRPs) in the division of the hydrogenosome. Eight DRP homologues [T.
      vaginalis DRPs (TvDRPs)], which can be grouped into 3 subclasses, are present in
      T. vaginalis. We examined 5 TvDRPs that are representative of each subclass, by
      introducing dominant negative mutations analogous to those known to interfere
      with mitochondrial division in yeast, worms, and mammals. Microscopic and cell
      fractionation analyses of parasites expressing one of the mutated TvDRPs
      (TVAG_350040) demonstrated that this protein localizes to hydrogenosomes.
      Moreover, these organelles were found to be increased in size and reduced in
      number in cells expressing this dominant negative protein, relative to parasites
      expressing the corresponding wild-type TvDRP, the other 4 mutant TvDRPs, or an
      empty vector control. Our data indicate a role for a TvDRP in the fission of T.
      vaginalis hydrogenosomes, similar to that described for peroxisomes and
      mitochondria. These findings reveal a conservation of core components involved in
      the division of diverse eukaryotic organelles across broad phylogenetic
      distances.

PMID- 24297698
TI  - The metabolic sensors FXRalpha, PGC-1alpha, and SIRT1 cooperatively regulate
      hepatitis B virus transcription.
AB  - Hepatitis B virus (HBV) genome transcription is highly dependent on liver
      enriched, metabolic nuclear receptors (NRs). Among others, NR farnesoid X
      receptor alpha (FXRalpha) enhances HBV core promoter activity and pregenomic RNA
      synthesis. Interestingly, two food-withdrawal-induced FXRalpha modulators,
      peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha)
      and deacetylase SIRT1, have been found to be associated with HBV genomes ex vivo.
      Whereas PGC-1alpha induction was shown to increase HBV replication, the effect of
      SIRT1 on HBV transcription remains unknown. Here, we showed that, in
      hepatocarcinoma-derived Huh-7 cells, combined activation of FXRalpha by GW4064
      and SIRT1 by activator 3 increased HBV core promoter-controlled luciferase
      expression by 25-fold, compared with a 10-fold increase with GW4064 alone. Using
      cell lines differentially expressing FXRalpha in overexpression and silencing
      experiments, we demonstrated that SIRT1 activated the core promoter in an
      FXRalpha- and PGC-1alpha-dependent manner. Maximal activation (>150-fold) was
      observed in FXRalpha- and PGC-1alpha-overexpressing Huh-7 cells treated with
      FXRalpha and SIRT1 activators. Similarly, in cells transfected with full-length
      HBV genomes, maximal induction (3.5-fold) of core promoter-controlled synthesis
      of 3.5-kb RNA was observed in the same conditions of transfection and treatments.
      Thus, we identified a subnetwork of metabolic factors regulating HBV replication,
      strengthening the hypothesis that transcription of HBV and metabolic genes is
      similarly controlled.

PMID- 24297699
TI  - Blocking the urotensin II receptor pathway ameliorates the metabolic syndrome and
      improves cardiac function in obese mice.
AB  - The metabolic syndrome is defined by the presence of hyperlipidemia, obesity,
      hypertension, and diabetes. The syndrome is associated with significant
      cardiovascular morbidity and mortality. The aim of the present study was to
      determine the role of the vasoactive peptide urotensin II (UII) in the
      pathogenesis of the metabolic syndrome. We used obese mice (ob/ob) to determine
      the effect of UII receptor (UT) blockage on the different facets of the metabolic
      syndrome with special emphasis on cardiac function. Our data demonstrate a
      significant increase in UII and UT expression in the myocardium of obese mice
      accompanied by a significant decrease in sarco/endoplasmic reticulum Ca(2+)
      ATPase 2a (SERCA2a) expression, as well as intracellular Na(+) and Ca(2+)
      compared with wild-type mice (P<0.05). Treatment of ob/ob mice with the UII
      receptor antagonist SB657510 significantly improved glucose levels, blood
      pressure, hyperlipidemia, expression of myocardial SERCA2a, intracellular Na(+)
      and Ca(2+) and cardiac function in association with a decrease in weight gain,
      and mammalian target of rapamycin (mTOR) and sodium/hydrogen exchanger 1 (NHE-1)
      protein expression compared with vehicle (P<0.05). These findings demonstrate an
      important role for UII in the pathogenesis of the metabolic syndrome and suggest
      that the use of UT receptor antagonists may provide a new therapeutic tool for
      the treatment of this syndrome.

PMID- 24297700
TI  - The SIRT1 deacetylase protects mice against the symptoms of metabolic syndrome.
AB  - Type 2 diabetes, hepatic steatosis, and gut dysbiosis are pathophysiological
      consequences of obesity. Sirtuin (SIRT)-1 is a protein deacetylase implicated in
      the regulation of metabolic activity. We set out to determine whether the
      catalytic activity of SIRT1 plays a role in the development of metabolic
      syndrome, hepatic steatosis, and the distribution of gut microbiota. We
      challenged with a high-fat diet (HFD) a strain of mice homozygous for a Sirt1
      allele carrying a point mutation that ablates the deacetylase activity of SIRT1.
      When compared to wild-type animals, mice lacking SIRT1 catalytic activity rapidly
      accumulated excessive hepatic lipid while fed the HFD, an effect evident within 2
      wk of HFD feeding. Both white and brown adipose depots became hypertrophic, and
      the animals developed insulin resistance. The ratio of the major phyla of gut
      microbiota (Firmicutes and Bacteroidetes) increased rapidly in the SIRT1
      deficient mice after HFD challenge. We conclude that the deacetylase activity of
      SIRT1 plays an important role in regulating glucose and hepatic lipid
      homeostasis. In addition, the composition of gut microbiota is influenced by both
      the animals' Sirt1 genotype and diet composition.

PMID- 24297701
TI  - BCR-ABL residues interacting with ponatinib are critical to preserve the
      tumorigenic potential of the oncoprotein.
AB  - Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs)
      fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack
      of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form
      hydrogen bonds with ponatinib. We therefore introduced mutations in each of these
      residues, either preserving or altering their physicochemical properties. We
      found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein
      stability but are critical for preserving catalytic activity. Indeed, only a
      "conservative" I360T substitution retained kinase proficiency and transforming
      potential. Molecular dynamics simulations of BCR-ABL(I360T) revealed differences
      in both helix alphaC dynamics and protein-correlated motions, consistent with a
      modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to
      ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4
      BCR-ABL residues described here would be selected against by a lack of kinase
      activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent
      to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases.
      Hence, these residues may represent an appealing target for the design of
      pharmacological compounds that would inhibit additional oncogenic tyrosine
      kinases while avoiding the emergence of resistance due to point mutations.

PMID- 24297702
TI  - A composite model of the human postcapillary venule for investigation of
      microvascular leukocyte recruitment.
AB  - Neutrophil extravasation occurs across postcapillary venules, structures composed
      of endothelial cells (ECs), pericytes (PCs), and basement membrane (BM). We
      constructed composite models of the human postcapillary venule, combining ECs
      with PCs or PC-deposited BM, to better study this process. Quiescent and tumor
      necrosis factor alpha (TNF-alpha)-activated composites demonstrated in situ-like
      expression of cadherins, E-selectin, intercellular adhesion molecule 1 (ICAM-1),
      vascular cell adhesion molecule 1 (VCAM-1), platelet-endothelial cell adhesion
      molecule 1 (PECAM-1), CD99, and interleukin 8 (IL-8). After TNF-alpha activation,
      the ECs supported greater neutrophil adhesion (66.1 vs. 23.7% of input cells) and
      transmigration (35.1 vs. 7.20% of input cells) than did the PCs, but the
      composites behaved comparably (no significant difference) to ECs in both assays.
      TNF-alpha-activated EC-conditioned medium (CM) increased transmigration across
      the PCs, whereas TNF-alpha-activated PC-CM decreased transmigration across the
      ECs, and culturing on PC-derived BM decreased both adhesion to and transmigration
      across the ECs. Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited
      adhesion to TNF-alpha-activated composites, but not to ECs alone. Anti-CD99
      (expressed on all 3 cell types) inhibited transmigration across the composites
      (14.5% of control) more than across the ECs (39.0% of control), and venular shear
      stress reduced transmigration across the ECs (17.3% of static) more than across
      the composites (36.7% of static). These results provide proof of concept that our
      composite human EC/PC/BM venular construct can reveal new interactions in the
      inflammatory cascade.

PMID- 24297703
TI  - Efficient generation of transgenic mice by lentivirus-mediated modification of
      spermatozoa.
AB  - Transgenic technologies conventionally rely on the oocyte as a substrate for
      genetic modification. Owing to their accessibility, however, male germ cells,
      including mature sperm, have material advantages for use in transgenesis. Here we
      have exploited lentiviruses to generate transgenic animals via the male germline.
      When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were
      incubated with mouse spermatozoa, these sperm were highly successful in producing
      transgenics. Lentivirally transduced mouse spermatozoa were used in in vitro
      fertilization (IVF) studies, and when followed by embryo transfer, >= 42% of
      founders were found to be transgenic for GFP. Inverse PCR strategy for
      integration site analysis demonstrated integration of at least 1 or 2 copies of
      GFP in the transgenics, mapping to different chromosomes. GFP expression was
      detected in a wide range of murine tissues, including testis and the transgene
      was stably transmitted to a third generation of transgenic animals. This
      relatively simple, yet highly efficient, technique for generating transgenic
      animals by transducing spermatozoa with lentiviral vectors in vitro is a powerful
      tool for the study of fertilization/preimplantation development, vertical viral
      gene transmission, gene function and regulation, and epigenetic inheritance.

PMID- 24297704
TI  - Cloning and identification of a novel NhaD-type Na+/H+ antiporter from
      metagenomic DNA of the halophilic bacteria in soil samples around Daban Salt
      Lake.
AB  - In this study, metagenomic DNA was screened for the Na(+)/H(+) antiporter gene
      from the halophilic bacteria in Daban Salt Lake by selection in Escherichia coli
      KNabc lacking three major Na(+)/H(+) antiporters. One gene designated as Hb_nhaD
      encoding a novel NhaD-type Na(+)/H(+) antiporter was finally cloned. The presence
      of Hb_NhaD conferred tolerance of E. coli KNabc to up to 0.5 M NaCl and 0.2 M
      LiCl, and an alkaline pH. Hb_NhaD has the highest identity (70.6%) with a
      putative NhaD-type Na(+)/H(+) antiporter from an uncharacterized Clostridiaceae
      species, and also has lower identity with known NhaD-type Na(+)/H(+) antiporters
      from Halomonas elongata (20.8%), Alkalimonas amylolytica (19.0%), Vibrio
      parahaemolyticus (18.9%) and Vibrio cholerae (18.7 %). pH-dependent
      Na(+)(Li(+))/H(+) antiport activity was detected from everted membrane vesicles
      prepared from E. coli KNabc carrying Hb_nhaD. Hb_NhaD exhibited very high
      Na(+)(Li(+))/H(+) antiport activity over a wide pH range from 6.5 to 9.0 with the
      highest activity at pH 7.0 which is significantly different from those of the
      above known NhaD-type Na(+)/H(+) antiporters. Also, the apparent K m values of
      Hb_NhaD for Na(+) and Li(+) at pH 7.0 were determined to be 1.31 and 2.16,
      respectively. Based on the above results, we proposed that Hb_NhaD should be
      categorized as a novel NhaD-type Na(+)/H(+) antiporter.

PMID- 24297705
TI  - Isolation and characterization of phage-host systems from the Baltic Sea ice.
AB  - In search for sea ice bacteria and their phages from the Baltic Sea ice, two ice
      samples were collected from land-fast ice in a south-west Finland coastal site in
      February and March 2011. Bacteria were isolated from the melted sea ice samples
      and phages were screened from the same samples for 43 purified isolates. Plaque
      producing phages were found for 15 bacterial isolates at 3  degrees C. Ten phage
      isolates were successfully plaque purified and eight of them were chosen for
      particle purification to analyze their morphology and structural proteins. Phage
      1/32 infecting an isolate affiliated to phylum Bacteroidetes (Flavobacterium sp.)
      is a siphovirus and six phages infecting isolates affiliated to gamma
      Proteobacteria (Shewanella sp.) hosts were myoviruses. Cross titrations between
      the hosts showed that all studied phages are host specific. Phage solutions, host
      growth and phage infection were tested in different temperatures revealing phage
      temperature tolerance up to 45  degrees C, whereas phage infection was in most of
      the cases retarded above 15  degrees C. This study is the first to report
      isolation and cultivation of ice bacteria and cold-active phages from the Baltic
      Sea ice.

PMID- 24297706
TI  - Macitentan: first global approval.
AB  - Macitentan (Opsumit(r)) is a novel dual endothelin receptor antagonist (ERA) with
      sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd.
      In October 2013, oral macitentan 10 mg once daily received its first global
      approval in the US, followed closely by Canada, for the treatment of pulmonary
      arterial hypertension (PAH). The drug has also received a positive opinion in the
      EU from the Committee for Medicinal Products for Human Use for the treatment of
      PAH, and is under regulatory review in several other countries for the same
      indication. Endothelin (ET)-1 influences pathological changes via two ET receptor
      subtypes (ETA and ETB), to which it binds with high affinity. ET-1 is implicated
      in several forms of vascular disease making it a valid target for the treatment
      of pulmonary vascular diseases such as PAH. Clinical development is underway for
      other indications, including Eisenmenger syndrome, ischaemic digital ulcers
      secondary to systemic sclerosis, and glioblastoma. Macitentan was also evaluated
      in idiopathic pulmonary fibrosis; however, a phase 2 trial did not meet its
      primary endpoint and further investigation in this indication was discontinued.
      Macitentan was developed by modifying the structure of bosentan in the search for
      an optimal dual ERA with improved efficacy and tolerability compared with other
      ERAs. This article summarizes the milestones in the development of macitentan
      leading to this first approval for PAH.

PMID- 24297707
TI  - Effect of alpha, beta momorcharin on viability, caspase activity, cytochrome c
      release and on cytosolic calcium levels in different cancer cell lines.
AB  - A multitude of plants have been used extensively for the treatment of cancers
      throughout the world. The protein, alpha, beta momorcharin has been extracted
      from the plant Momordica charantia (MC), and it possesses anti-cancer and anti
      HIV properties similar to the crude water and methanol soluble extract of the
      plant. This study investigated the anti-cancer effects and the cellular
      mechanisms of action of alpha, beta momocharin (200-800 MUM) on 1321N1, Gos-3,
      U87-MG, Sk Mel, Corl-23 and Weri Rb-1 cancer cell lines compared to normal
      healthy L6 muscle cell line measuring cell viability using MTT assay kit, Caspase
      3 and 9 activities, cytochrome c release and intracellular free calcium
      concentrations [Ca(2+)]i. The results show that alpha, beta momorcharin can evoke
      significant dose-dependent (P < 0.05; Student's t test) decreases in the
      viability (increases in cell death) of 1321N1, Gos-3, U87-MG, Sk Mel, Corl-23 and
      Weri Rb-1 cancer cell lines compared to healthy L6 muscle cell line and untreated
      glioma cells. alpha, beta momorcharin (800 MUM) also evoked significant (P <
      0.05) increases in caspase-3 and 9 activities and cytochrome c release.
      Similarly, alpha, beta momorcharin elicited significant (P < 0.05) time-dependent
      elevation in [Ca(2+)]i in all five glioma cell lines compared to untreated cells.
      Together, the results have demonstrated that alpha, beta momorcharin can exert
      its anti-cancer effect on different cancer cell lines by intracellular processes
      involving an insult to the mitochondria resulting in cellular calcium over
      loading, apoptosis, cytochrome release and subsequently, cell death. 

PMID- 24297708
TI  - Factors influencing post-coronary artery bypass grafting atrial fibrillation
      episodes.

PMID- 24297709
TI  - Coronary artery tortuosity: comparison with retinal arteries and carotid intima
      media thickness.
AB  - BACKGROUND AND AIM: We conducted a prospective study to investigate the possible
      relationship between the tortuosity of coronary arteries (TCA) and carotid intima
      media thickness (CIMT), and also compare TCA to retinal artery tortuosity.
      METHODS: One hundred and five participants with nonsignificant coronary plaque or
      normal coronary angiogram were included. To determine subclinical
      atherosclerosis, maximum CIMT was measured. Retinal tortuosity was evaluated
      ophthalmically. RESULTS: Among all demographic variables and risk factors, only
      female gender and height were significantly associated with TCA (p = 0.001, p =
      0.01, respectively). Retinal artery tortuosity and retinal artery atherosclerosis
      were more common inpatients with TCA compared to patients without TCA (p < 0.001,
      R = 0.6; p = 0.002, R = 0.4, respectively). CIMT was greater in participants with
      TCA than patients without TCA (p = 0.001), and also the presence of carotid
      artery plaque was more common in patients with TCA (p < 0.001). There was a
      significant correlation between the presence of subclinical atherosclerosis and
      TCA (p = 0.005, R = 0.3). Likewise, a significant correlation was found between
      subclinical atherosclerosis and retinal artery tortuosity (p = 0.02, R = 0.3).
      Multivariate analysis identified female gender (p < 0.008), retinal
      arterytortuosity (p < 0.001), and CIMT (p = 0.02) as independent predictors of
      TCA. CONCLUSIONS: These results indicate that, whatever the mechanism is: 1) TCA
      is associated with female gender and short stature; 2) TCA is associated with
      subclinical atherosclerosis even in patients with entirely normal appearing
      coronary arteries on coronary angiography; 3) Retinal artery tortuosity is
      correlated with TCA and can be a surrogate for systemic arterial tortuosity.

PMID- 24297710
TI  - The relationship between platelet indices and clinical features of coronary
      artery disease.
AB  - BACKGROUND: Platelets play a key role in the development and progression of
      cardiovascular disease. The degree of platelet activation may be assessed by
      platelet indices such as platelet count, mean platelet volume (MPV) and platelet
      distribution width (PDW). AIM: To evaluate the relationship between platelet
      indices and clinical features of coronary artery disease (CAD). METHODS: Our
      population is represented by a total of 441 consecutive patients undergoing
      coronary angiography. Patients were divided into three groups according to their
      clinical presentation: Patients with stable angina (Group I), with acute coronary
      syndrome (Group II), and with a normal coronary angiogram (Group III). All
      demographic and clinical features were collected retrospectively. Platelet
      indices were measured in all patients. RESULTS: There was no statistical
      difference for platelet count, MPV and PDW values among the groups. Correlation
      analysis showed a positive association between platelet count and Gensini scoring
      (Kendall's tau b, r = 0.312, p = 0.037, two-tailed)and also age (Kendall's tau b,
      r = 0.518, p = 0.001, two-tailed) in patients with CAD. However, there was no
      significant correlation between Gensini scoring and MPV or PDW values in these
      patients. CONCLUSIONS: PDW and MPV may not be related to the clinical features or
      presentation and extent of CAD. Our study findings add to the conflicting results
      of previous studies in this area. Prospective trials with longer follow-up
      periods and larger samples are warranted to conclusively define the role of
      platelet indices in CAD.

PMID- 24297711
TI  - Outpatient oral anticoagulation in Poland in 2012: a single centre experience.
AB  - BACKGROUND: Oral anticoagulants reduce embolic complications in patients with
      atrial fibrillation (AF) and are used in the treatment and prevention of venous
      thromboembolism. In Poland, chronic oral anticoagulation is usually managed by
      primary care physicians, and the most commonly used drugs are vitamin K
      antagonists (VKA). AIM: To evaluate effectiveness of oral anticoagulation in 104
      patients receiving chronic VKA treatment in primary care from Jan 01, 2011 to Dec
      31, 2011. METHODS: We performed a retrospective analysis of data of 104 patients
      receiving chronic VKA treatment in a primary care practice (Niepubliczny Zaklad
      Opieki Zdowotnej ESCULAP Gniewkowo) from Jan 01, 2011 to Dec 31, 2011. These
      patients comprised 1.1% of the population remaining under care of this primary
      care practice. We determined minimum, maximum and mean values of the
      international normalised ratio (INR), the proportion of results within the
      therapeutic range, the number of INR measurements, and indications for
      anticoagulant treatment. In patients with AF, we determined the risks of bleeding
      complications and thrombotic events. RESULTS: Among patients receiving chronic
      VKA treatment, 56.84% of INR measurements were within the therapeutic range. Only
      29.8% of patients had more than 70% of INR measurements within the therapeutic
      range. We found no association between the number of INR measurements and
      treatment effectiveness. CONCLUSIONS: The effectiveness of anticoagulation in
      primary care is unsatisfactory. In our study population, an acceptable time in
      the therapeutic range was achieved in only just below 30% of patients.

PMID- 24297712
TI  - Does a high percentage of right ventricular pacing influence the incidence of
      paroxysmal atrial fibrillation in myotonic dystrophy type 1 patients?
AB  - BACKGROUND: Paroxysmal atrial tachyarrhythmias occur frequently in myotonic
      dystrophy type 1 (MD1) patients. Pacemakers, implanted for the treatment of
      bradyarrhythmias and including detailed diagnostic functions, may facilitate the
      diagnosis and management of frequent paroxysmal atrial fibrillation (AF) that may
      remain undetected during a conventional clinical follow-up. The effect of right
      ventricular pacing on AF incidence is still controversial. AIM: To evaluate the
      influence of a high percentage of right ventricular pacing on AF in MD1 patients
      during a 12-month follow-up period. METHODS: We enrolled in the present study 70
      MD1 patients (age 51.3 +/- 5 years; 32 females) who underwent dual chamber
      pacemaker implantation. At 12 months of follow-up, the study population was
      divided into three groups according to the percentage of atrial and ventricular
      stimulation: Group 1, the atrial sensing ventricular sensing group (ASVS; n = 22;
      age 52 +/- 7.7; eight female) with a percentage of atrial and ventricular
      stimulation lower than 50%; Group 2, the atrial sensing ventricular pacing group
      (ASVP; n = 24; age 50.5 +/- 7.6; 13 female) with a percentage of atrial
      stimulation lower than 50% and percentage of ventricular stimulation higher than
      80%; and Group 3, the atrial pacing ventricular pacing group (APVP; n = 24; age
      56 +/- 4.3; 11 female) with a percentage of atrial and ventricular stimulation
      higher than 80%. We counted the number of episodes of atrial arrhythmia that
      occurred during the observation period and the duration of each episode. RESULTS:
      We found a statistically significant difference in the number and duration of AF
      episodes between the three groups at the 12-month follow-up. In particular, there
      were more episodes (253 +/- 30 vs. 80 +/- 27 vs. 53 +/- 32; p < 0.03) and longer
      durations of AF (8,700 +/- 630 vs. 4,480 +/- 975 vs. 3,853 +/- 870 min; p < 0.03)
      in the ASVP group than in the ASVS group and the APVP group. Lead parameters
      remained stable over time and there were no displacements of the electrodes after
      implantation. CONCLUSIONS: In a 12-month follow-up comparison, we showed a
      statistically significant increase in paroxysmal AF episodes in MD1 patients with
      a high percentage of right ventricular pacing and a lower percentage of atrial
      stimulation.

PMID- 24297713
TI  - Doppler tissue imaging assessment of myocardial velocities and atrioventricular
      time intervals in term newborn infants during the neonatal period.
AB  - BACKGROUND: In both term and premature neonates, changes in the systolic and
      diastolic function of the left ventricle (LV) and right ventricle (RV) reflect
      the degree of neonatal myocardial immaturity and the co-existence of foetal
      circulation as well as the presence of concurrent diseases. AIM: To evaluate the
      changes in values of systolic and diastolic LV and RV function using pulse tissue
      Doppler imaging (TDI) in 20 healthy term newborn infants from birth to the 28th
      day of life. METHODS: Ventricular peak myocardial velocities were recorded during
      early diastole (Em wave), atrial contraction (Am wave), and systole (Sm wave).
      TDI derived atrioventricular (AV) intervals were measured as the period from
      atrial contraction (Am) to isovolumic contraction (IV), from Am to ventricular
      systole (Sm), from Sm to the following Am, and from IV to the following Am. The
      first measurements were taken as soon as possible after birth, the second on the
      third day, and the final one on the 28th day of life. RESULTS: The diastolic
      myocardial velocities recorded in the RV were higher than those in the LV.
      Statistically significant differences were observed for time intervals in the RV:
      Am-IV and Am-Sm (day 1-3), p < 0.02; IV-Am (day 1-28), p < 0.005; Sm-Am (day 1
      28), p < 0.01. Statistically significant differences for time intervals were also
      evident in the LV: Am-IV (day 1-28), p < 0.05; and for Sm-Am (day 1-28), p <
      0.01. Mean isovolumetric contraction time (ICT) and isovolumetric relaxation time
      (IRT) intervals remained stable for all measurements recorded in the RV. However,
      a statistically significant difference was evident for both ICT and IRT intervals
      in the LV between days 1 and 28 of life (p < 0.01). CONCLUSIONS: 1. Cardiac TDI
      is feasible in the neonate. 2. In neonates, the diastolic and systolic function
      recorded in the RV was better than that in the LV. This may reflect the
      'persistent' foetal status of this ventricle in the first day of life. 3. The
      differences observed in conduction times also reflect the haemodynamic changes
      which occur in the circulatory system of the neonate in the first month of life.
      4. Further investigation of a larger population of neonates throughout the whole
      neonatal period is indicated.

PMID- 24297715
TI  - [Twiddler's syndrome: a new face of the old problem].
AB  - Twiddler's syndrome (TS) is the well known late electrotherapy complication. The
      typical TS develops as a result of the pulse generator rotation with retraction
      of the leads and consequent interruption of pacing. We reported 2 cases
      illustrating late TS without spontaneous old, ingrown lead extraction and very
      different leads damage. 

PMID- 24297714
TI  - The prevalence of sexual dysfunction before myocardial infarction in population
      of Polish men: a retrospective pilot study.
AB  - BACKGROUND AND AIM: To assess the frequency of sexual dysfunction in men before
      myocardial infarction (MI). METHODS: Sixty-two men with cardiovascular disease
      risk factors who were admitted to the hospital because of a first MI, were asked
      to fill the IIEF-15 questionnaire to assess sexual dysfunction before MI.
      RESULTS: Erectile dysfunction (ED), decreased orgasmic function, decreased sexual
      desire, decreased intercourse satisfaction, and decreased overall satisfaction
      were reported by 51.6%, 14.5%, 50%, 69.4%, and 48.4% of men, respectively. Men
      with ED had significantly higher serum C-reactive protein (CRP) levels than men
      without ED (5.8 mg/L, 95% confidence interval [CI] 8.3-21.7) vs. 4.6 mg/L, 95% CI
      3.0-11.3; p = 0.01). Men with decreased orgasmic function had significantly
      higher serum triglyceride levels (259.5 mg/dL, 95% CI 176.9-362.1 vs. 150 mg/dL,
      95% CI 146.8-187.4; p = 0.01), and men with normal sexual desire had
      significantly higher serum high-density lipoprotein (HDL) cholesterol levels than
      men with decreased sexual desire (41 mg/dL, 95% CI 39.9-47.8 vs. 36 mg/dL, 95% CI
      34.1-40.5; p = 0.01). Men with decreased sexual desire had significantly higher
      serum CRP levels (7 mg/L, 95% CI 7.7-21.4 vs. 5 mg/L, 95% CI 3.6-12.1; p = 0.03).
      CONCLUSIONS: 1. ED was present in more than half of men before MI and it may be
      the first symptom of coronary artery disease. 2. Men with ED and decreased sexual
      desire have higher serum CRP levels in the acute peri-infarction period. 3. Serum
      triglyceride level is a factor that significantly affects orgasmic function, and
      serum HDL cholesterol level is a factor that significantly affects sexual desire.

PMID- 24297716
TI  - Treatment of a primary cardiac lymphoma with orthotopic heart transplantation.
AB  - We here describe the case of a patient diagnosed with primary lymphoma who
      underwent orthotopic heart transplantation.Post surgically, the patient was
      treated with immunosuppressants and chemotherapy. Three months later, lesions
      were found on the right side of the neck and the inferior vena cava; 12 months
      later, the lesion of the neck became smaller and the lesion of the inferior vena
      cava was not detected by positron emission tomography/computed tomography. The
      problems we encountered with this rare disease are discussed and compared to
      previous studies.

PMID- 24297717
TI  - Pulmonary artery aneurysm mimicking pulmonary artery dissection detected by
      multimodality imaging.
AB  - An idiopathic pulmonary artery aneurysm (PAA) is an uncommon lesion, and is
      defined when the diameter of the pulmonary trunk is greater than 30 mm in the
      absence of cardiac or pulmonary etiologies. Idiopathic PAA is generally
      asymptomatic and has an increased risk for dissection or rupture of the aneurysm.
      We herein demonstrate two- and three-dimensional echocardiographic and
      computerised tomographic angiography features of an idiopathic pulmonary aneurysm
      mimicking a pulmonary artery dissection. 

PMID- 24297718
TI  - Cardiovascular diseases associated with HIV infection and their management.

PMID- 24297719
TI  - Electrocardiographic landmarks of hypothermia.
AB  - We present the cases of two patients with hypothermia, with a detailed
      description of electrocardiographic changes associated with hypothermia. In both
      cases, J wave was initially misdiagnosed as left bundle branch block (LBBB). We
      discuss the differentiation of J wave from LBBB. 

PMID- 24297720
TI  - About hypothermal J wave.

PMID- 24297721
TI  - [Abnormal filter setting or Brugada syndrome?].
AB  - 26-year old patient was admitted to our department with suspected Brugada
      syndrome (BrS). He complained of recurrent dizziness due to which he was taken by
      a team of rescuers to the district hospital, where the recorded ECG demonstrated
      isolated 3-7 mm ST segment elevation in leads V1-V3. Coronary angiography
      performed in this hospital was normal. Then patient was transferred to our
      department for consideration of ICD implantation. ECG registration in our
      hospital with 0.05 Hz (3.2 s) filter showed sinus bradycardia with 1-2 mm ST
      segment elevation in precordial leads. A detailed analysis of all ECG's proved
      that the district hospital ECG was performed in manual mode with the application
      of 1.5 Hz (0.1 s) low frequency high-pass filter. To confirm the effect of
      incorrect filter as the cause of misdiagnosis we repeated ECG recording using the
      recorder which allows to apply the same settings 1.5 Hz (0.1 s) as in district
      hospital and reconstructed ECG with repolarisation abnormalities. Negative
      ajmaline test (1 mg/kg) additionally reaffirmed an exclusion of dynamic form of
      BrS.

PMID- 24297722
TI  - [Cardiac contemporary imaging during pregnancy. Expert consensus statement of the
      Polish Clinical Forum for Cardiovascular Imaging].

PMID- 24297723
TI  - [Atrial fibrillation in patient with concealed Wolff-Parkinson-White syndrome].
AB  - We present a case of 33-year-old woman suffered from palpitations and syncope.
      ECG was normal at the rest and showed irregular tachycardia with wide QRS complex
      (HR > 300/min) during the effort. The patient was admitted to our department in
      order to perform detailed diagnostics and therapy. Based on electrophysiological
      study we found and ablated numerous concealed accessory pathways. During 1 year
      observation patient stay assymptomatic.

PMID- 24297724
TI  - Percutaneous patent foramen ovale closure in a patient with inferior vena cava
      filter.

PMID- 24297725
TI  - The dramatic course of dissection of a giant thoracic aortic aneurysm.

PMID- 24297726
TI  - Right pulmonary artery aplasia with coronary collaterals supplying a hypoplastic
      lung.

PMID- 24297727
TI  - Lysis of thrombus located in the left atrial appendage. Is it the right time for
      a Xa factor inhibitor?

PMID- 24297728
TI  - Paravalvular aortic regurgitation as the reason for second CoreValve
      bioprosthesis implantation in a patient with native bicuspid valve.

PMID- 24297729
TI  - Acute respiratory failure due to giant aortic aneurysm mimicking massive
      pulmonary embolism in a patient with Marfan's syndrome.

PMID- 24297730
TI  - [Interventional cardiology in Poland in the year 2012. Summary report of the
      Association of Cardiovascular Interventions of the Polish Cardiac Society].

PMID- 24297731
TI  - [Comment on the article: "Ruptured aneurysm of the sinus of Valsalva manifesting
      as acute heart failure" published in "Kardiologia Polska" 2013;71,9:993].

PMID- 24297732
TI  - [ESC guidelines on diabetes, pre-diabetes and diseases of the cardiovascular
      system developed in cooperation with the EASD].

PMID- 24297733
TI  - Influence of age, sex and genetic factors on the human brain.
AB  - We report effects of age, age(2), sex and additive genetic factors on variability
      in gray matter thickness, surface area and white matter integrity in 1,010
      subjects from the Genetics of Brain Structure and Function Study. Age was more
      strongly associated with gray matter thickness and fractional anisotropy of water
      diffusion in white matter tracts, while sex was more strongly associated with
      gray matter surface area. Widespread heritability of neuroanatomic traits was
      observed, suggesting that brain structure is under strong genetic control.
      Furthermore, our findings indicate that neuroimaging-based measurements of
      cerebral variability are sensitive to genetic mediation. Fundamental studies of
      genetic influence on the brain will help inform gene discovery initiatives in
      both clinical and normative samples. 

PMID- 24297734
TI  - Nuclear FKBPs, Fpr3 and Fpr4 affect genome-wide genes transcription.
AB  - Fpr3 and Fpr4 of Saccharomyces cerevisiae are nuclear FK506-binding proteins each
      containing an extended acidic domain in addition to the conserved FK506
      binding/peptidylprolyl isomerase (PPIase) domain. Previous studies have shown
      that the PPIase domain regulates histone H3 methylation, while the acidic domain
      facilitates histone deposition and may regulate rDNA silencing. To gain insight
      into the role of FKBPs in maintaining chromatin structure, we examined the
      transcriptional profiles of fpr3 (-) and fpr4 (-) cells. Our results show that
      both proteins modulate the expression of a large number of genes randomly
      distributed throughout the genome, a pattern resembling those observed with yeast
      cells lacking other histone chaperones such as CAF1 and Asf1. Significant
      overlaps are found between nuclear FKBPs-modulated and the Asf1/CAF1-modulated
      genes. Thus, nuclear FKBPs appear to impact chromatin structure like other
      histone chaperones. Our analyses show that depleting Fpr4 causes no detectable
      chromatin structural change at the rDNA locus nor de-repression of transcription
      silencing at the locus, in contrast to a previous report. Furthermore, we
      demonstrate PPIase domain of the proteins represses transcription when tethered
      to the promoter of a reporter gene, suggesting that the PPIase domains can act on
      non-histone chromatin components, when brought to close proximity. The results
      thus provide a further demonstration for the elusive role of Fpr3 and Fpr4 in
      histone chaperones. 

PMID- 24297736
TI  - GE beta-amyloid agent approved.

PMID- 24297742
TI  - NIH focuses on the brain.

PMID- 24297735
TI  - Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear
      factor-kappaB-mediated inflammation in macrophages.
AB  - RATIONALE: Mitochondrial oxidative stress (mitoOS) has been shown to correlate
      with the progression of human atherosclerosis. However, definitive cell type
      specific causation studies in vivo are lacking, and the molecular mechanisms of
      potential proatherogenic effects remain to be determined. OBJECTIVE: Our aims
      were to assess the importance of macrophage mitoOS in atherogenesis and to
      explore the underlying molecular mechanisms. METHODS AND RESULTS: We first
      validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS
      atherosclerosis association by showing that non-nuclear oxidative DNA damage, a
      marker of mitoOS in lesional macrophages, correlates with aortic root lesion
      development. To investigate the importance of macrophage mitoOS, we used a
      genetic engineering strategy in which the OS suppressor catalase was ectopically
      expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages
      was successfully suppressed in these mice, and this led to a significant
      reduction in aortic root lesional area. The mCAT lesions had less monocyte
      derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels
      of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic
      protein-1 was associated with the suppression of other markers of inflammation
      and with decreased phosphorylation of RelA (NF-kappaB p65), indicating decreased
      activation of the proinflammatory NF-kappaB pathway. Using models of mitoOS in
      cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein
      1 expression by decreasing the activation of the IkappaB-kinase beta-RelA NF
      kappaB pathway. CONCLUSIONS: MitoOS in lesional macrophages amplifies
      atherosclerotic lesion development by promoting NF-kappaB-mediated entry of
      monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis
      link in human atheromata, these findings reveal a potentially new therapeutic
      target to prevent the progression of atherosclerosis.

PMID- 24297743
TI  - Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Resistance and aerobic exercises are both recommended as effective
      treatments for people with type 2 diabetes. However, the optimum type of exercise
      for the disease remains to be determined to inform clinical decision-making and
      facilitate personalized exercise prescription. OBJECTIVES: Our objective was to
      investigate whether resistance exercise is comparable to aerobic exercise in
      terms of effectiveness and safety in people with type 2 diabetes. DATA SOURCES:
      PubMed, EMBASE, CENTRAL, CINAHL, and SPORTdiscus were systematically searched up
      to March 2013. The reference lists of eligible studies and relevant reviews were
      also checked. STUDY SELECTION: We used the following criteria to select studies
      for inclusion in the review: (i) the study was a randomized controlled trial;
      (ii) the participants were people with type 2 diabetes aged 18 years or more;
      (iii) the trial compared resistance exercise with aerobic exercise for a duration
      of at least 8 weeks, with pre-determined frequency, intensity, and duration; and
      (iv) the trial provided relevant data on at least one of the following: glycaemic
      control, blood lipids, anthropometric measures, blood pressure, fitness, health
      status, and adverse events. STUDY APPRAISAL AND SYNTHESIS METHODS: The assessment
      of study quality was based on the Cochrane Risk of Bias tool. For effectiveness
      measures, differences (resistance group minus aerobic group) in the changes from
      baseline with the two exercises were combined, using a random-effects model
      wherever possible. For adverse events, the relative risks (resistance group vs.
      aerobic group) were combined. RESULTS: Twelve trials (n = 626) were included.
      Following the exercise interventions, there was a greater reduction of
      glycosylated hemoglobin with aerobic exercise than with resistance exercise
      (difference 0.18% (1.97 mmol/mol), 95% confidence interval (CI) 0.01, 0.36). This
      difference became non-significant with sensitivity analysis (p = 0.14). The
      differences in changes from baseline were also statistically significant for body
      mass index (difference 0.22, 95% CI 0.06, 0.39), peak oxygen consumption
      (difference -1.84 mL/kg/min, 95% CI -3.07, -0.62), and maximum heart rate
      (difference 3.44 beats per minute, 95% CI 2.49, 4.39). Relative risks for adverse
      events (all) and serious adverse events were 1.17 (95% CI 0.77, 1.79) and 0.89
      (95% CI 0.18, 4.39), respectively. LIMITATIONS: Most included trials were short
      term (8 weeks to 6 months), and seven had important methodological limitations.
      Additionally, the meta-analyses for some of the secondary outcomes had a small
      number of participants or substantial statistical heterogeneity. CONCLUSIONS:
      Although differences in some diabetic control and physical fitness measures
      between resistance exercise and aerobic exercise groups reached statistical
      significance, there is no evidence that they are of clinical importance. There is
      also no evidence that resistance exercise differs from aerobic exercise in impact
      on cardiovascular risk markers or safety. Using one or the other type of exercise
      for type 2 diabetes may be less important than doing some form of physical
      activity. Future long-term studies focusing on patient-relevant outcomes are
      warranted.

PMID- 24297744
TI  - Reliable and valid assessment of Lichtenstein hernia repair skills.
AB  - PURPOSE: Lichtenstein hernia repair is a common surgical procedure and one of the
      first procedures performed by a surgical trainee. However, formal assessment
      tools developed for this procedure are few and sparsely validated. The aim of
      this study was to determine the reliability and validity of an assessment tool
      designed to measure surgical skills in Lichtenstein hernia repair. METHODS: Key
      issues were identified through a focus group interview. On this basis, an
      assessment tool with eight items was designed. Ten surgeons and surgical trainees
      were video recorded while performing Lichtenstein hernia repair, (four experts,
      three intermediates, and three novices). The videos were blindly and individually
      assessed by three raters (surgical consultants) using the assessment tool. Based
      on these assessments, validity and reliability were explored. RESULTS: The
      internal consistency of the items was high (Cronbach's alpha = 0.97). The inter
      rater reliability was very good with an intra-class correlation coefficient (ICC)
      = 0.93. Generalizability analysis showed a coefficient above 0.8 even with one
      rater. The coefficient improved to 0.92 if three raters were used. One-way
      analysis of variance found a significant difference between the three groups
      which indicates construct validity, p < 0.001. CONCLUSIONS: Lichtenstein hernia
      repair skills can be assessed blindly by a single rater in a reliable and valid
      fashion with the new procedure-specific assessment tool. We recommend this tool
      for future assessment of trainees performing Lichtenstein hernia repair to ensure
      that the objectives of competency-based surgical training are met.

PMID- 24297745
TI  - Platelet-larger cell ratio and the risk of periprocedural myocardial infarction
      after percutaneous coronary revascularization.
AB  - Periprocedural myocardial infarction (PMI) represents a frequent complication in
      patients undergoing percutaneous coronary revascularization. Despite great
      attention focused on pharmacological prevention of periprocedural damage, very
      little is known about using biomarkers to potentially predict the risk of PMI.
      Larger platelets have been associated with enhanced reactivity, increased
      cardiovascular risk, and higher rates of complications after coronary stenting.
      The platelet-larger cell ratio (P-LCR) identifies the largest-sized fraction of
      platelets, the proportion potentially more closely related to thrombotic events.
      The present study evaluated the relationship between P-LCR and PMI. We included
      1,285 patients undergoing PCI. Myonecrosis biomarkers were dosed at intervals
      from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I
      increase by three times the upper limit of normal (ULN) or by 50 % of an elevated
      baseline value, whereas PMI was defined as an increase in creatine kinase MB by 3
      * ULN or 50 % of baseline. We grouped patients according to tertile values of P
      LCR (<27.5; >=35.1). Higher P-LCR was associated with age (P = 0.01), diabetes (P
      = 0.001), previous cerebrovascular accidents (P = 0.007), therapy with statins (P
      < 0.001), angiotensin receptor blockers (P < 0.001), aspirin (P = 0.002), and
      nitrates (P = 0.01). P-LCR was related to hemoglobin levels (P < 0.001), and
      inversely related to platelet count (P < 0.001) and glycemia (P = 0.05). Patients
      with higher P-LCR had a lower presence of coronary thrombus (P = 0.003). Higher P
      LCR values did not increase the risk of PMI (P = 0.10; adjusted odds ratio (OR)
      (95 % confidence interval (CI)) = 0.97 (0.69-1.38)), P = 0.89) or periprocedural
      myonecrosis (P = 0.96; adjusted OR (95 % CI) = 1.003 (0.76-1.32), P = 0.99).
      Results were confirmed even in higher-risk subgroups of patients. P-LCR does not
      increase the risk of periprocedural myocardial infarction and myonecrosis in
      patients undergoing coronary stenting. 

PMID- 24297746
TI  - beta-Globin cis-elements determine differential nuclear targeting through
      epigenetic modifications.
AB  - Increasing evidence points to nuclear compartmentalization as a contributing
      mechanism for gene regulation, yet mechanisms for compartmentalization remain
      unclear. In this paper, we use autonomous targeting of bacterial artificial
      chromosome (BAC) transgenes to reveal cis requirements for peripheral targeting.
      Three peripheral targeting regions (PTRs) within an HBB BAC bias a competition
      between pericentric versus peripheral heterochromatin targeting toward the
      nuclear periphery, which correlates with increased H3K9me3 across the beta-globin
      gene cluster and locus control region. Targeting to both heterochromatin
      compartments is dependent on Suv39H-mediated H3K9me3 methylation. In different
      chromosomal contexts, PTRs confer no targeting, targeting to pericentric
      heterochromatin, or targeting to the periphery. A combination of fluorescent in
      situ hybridization, BAC transgenesis, and knockdown experiments reveals that
      peripheral tethering of the endogenous HBB locus depends both on Suv39H-mediated
      H3K9me3 methylation over hundreds of kilobases surrounding HBB and on G9a
      mediated H3K9me2 methylation over flanking sequences in an adjacent lamin
      associated domain. Our results demonstrate that multiple cis-elements regulate
      the overall balance of specific epigenetic marks and peripheral gene targeting. 

PMID- 24297747
TI  - Loss of centrioles causes chromosomal instability in vertebrate somatic cells.
AB  - Most animal cells contain a centrosome, which comprises a pair of centrioles
      surrounded by an ordered pericentriolar matrix (PCM). Although the role of this
      organelle in organizing the mitotic spindle poles is well established, its
      precise contribution to cell division and cell survival remains a subject of
      debate. By genetically ablating key components of centriole biogenesis in chicken
      DT40 B cells, we generated multiple cell lines that lack centrioles. PCM
      components accumulated in acentriolar microtubule (MT)-organizing centers but
      failed to adopt a higher-order structure, as shown by three-dimensional
      structured illumination microscopy. Cells without centrioles exhibited both a
      delay in bipolar spindle assembly and a high rate of chromosomal instability.
      Collectively, our results expose a vital role for centrosomes in establishing a
      mitotic spindle geometry that facilitates correct kinetochore-MT attachments. We
      propose that centrosomes are essential in organisms in which rapid segregation of
      a large number of chromosomes needs to be attained with fidelity. 

PMID- 24297748
TI  - The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN
      1 at the nuclear periphery.
AB  - Telomeres are specialized protein-DNA structures that protect chromosome ends. In
      budding yeast, telomeres form clusters at the nuclear periphery. By imaging
      telomeres in embryos of the metazoan Caenorhabditis elegans, we found that
      telomeres clustered only in strains that had activated an alternative telomere
      maintenance pathway (ALT). Moreover, as in yeast, the unclustered telomeres in
      wild-type embryos were located near the nuclear envelope (NE). This bias for
      perinuclear localization increased during embryogenesis and persisted in
      differentiated cells. Telomere position in early embryos required the NE protein
      SUN-1, the single-strand binding protein POT-1, and the small ubiquitin-like
      modifier (SUMO) ligase GEI-17. However, in postmitotic larval cells, none of
      these factors individually were required for telomere anchoring, which suggests
      that additional mechanisms anchor in late development. Importantly, targeted POT
      1 was sufficient to anchor chromatin to the NE in a SUN-1-dependent manner,
      arguing that its effect at telomeres is direct. This high-resolution description
      of telomere position within C. elegans extends our understanding of telomere
      organization in eukaryotes. 

PMID- 24297749
TI  - CP110 exhibits novel regulatory activities during centriole assembly in
      Drosophila.
AB  - CP110 is a conserved centriole protein implicated in the regulation of cell
      division, centriole duplication, and centriole length and in the suppression of
      ciliogenesis. Surprisingly, we report that mutant flies lacking CP110
      (CP110Delta) were viable and fertile and had no obvious defects in cell division,
      centriole duplication, or cilia formation. We show that CP110 has at least three
      functions in flies. First, it subtly influences centriole length by counteracting
      the centriole-elongating activity of several centriole duplication proteins.
      Specifically, we report that centrioles are ~10% longer than normal in CP110Delta
      mutants and ~20% shorter when CP110 is overexpressed. Second, CP110 ensures that
      the centriolar microtubules do not extend beyond the distal end of the centriole,
      as some centriolar microtubules can be more than 50 times longer than the
      centriole in the absence of CP110. Finally, and unexpectedly, CP110 suppresses
      centriole overduplication induced by the overexpression of centriole duplication
      proteins. These studies identify novel and surprising functions for CP110 in vivo
      in flies.

PMID- 24297750
TI  - The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP
      granules.
AB  - RNA localization pathways direct numerous mRNAs to distinct subcellular regions
      and affect many physiological processes. In one such pathway the tumor-suppressor
      protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions,
      forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that
      APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in
      sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP
      localization but is required for efficient translation of associated transcripts.
      Labeling of newly synthesized proteins revealed that Fus promotes translation
      preferentially within protrusions. Mutations in Fus cause amyotrophic lateral
      sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond
      to stress granules. We show that overexpression or mutation of Fus results in
      formation of granules, which preferentially recruit APC-RNPs. Remarkably, these
      granules are not translationally silent. Instead, APC-RNP transcripts are
      translated within cytoplasmic Fus granules. These results unexpectedly show that
      translation can occur within stress-like granules. Importantly, they identify a
      new local function for cytoplasmic Fus with implications for ALS pathology. 

PMID- 24297751
TI  - Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT.
AB  - The neural crest, an embryonic stem cell population, initially resides within the
      dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal
      transition (EMT) to commence migration. Although neural crest and cancer EMTs are
      morphologically similar, little is known regarding conservation of their
      underlying molecular mechanisms. We report that Sip1, which is involved in cancer
      EMT, plays a critical role in promoting the neural crest cell transition to a
      mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest
      cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally
      retained in the dorsal neuroepithelium, whereas Sox10, which is normally required
      for emigration, was diminished. Subsequently, clumps of adherent neural crest
      cells remained adjacent to the neural tube and aberrantly expressed E-cadherin
      while lacking N-cadherin. These findings demonstrate two distinct phases of
      neural crest EMT, detachment and mesenchymalization, with the latter involving a
      novel requirement for Sip1 in regulation of cadherin expression during completion
      of neural crest EMT. 

PMID- 24297753
TI  - L-tyrosine induces DNA damage in brain and blood of rats.
AB  - Mutations in the tyrosine aminotransferase gene have been identified to cause
      tyrosinemia type II which is inherited in an autosomal recessive manner. Studies
      have demonstrated that an excessive production of ROS can lead to reactions with
      macromolecules, such as DNA, lipids, and proteins. Considering that the L
      tyrosine may promote oxidative stress, the main objective of this study was to
      investigate the in vivo effects of L-tyrosine on DNA damage determined by the
      alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar
      rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine
      injection (500 mg/kg) or saline. For chronic administration, the animals received
      two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline
      administered for 24 days starting at postnatal day (PD) 7 (last injection at PD
      31), 12 h after the last injection, the animals were killed by decapitation. We
      observed that acute administration of L-tyrosine increased DNA damage frequency
      and damage index in cerebral cortex and blood when compared to control group.
      Moreover, we observed that chronic administration of L-tyrosine increased DNA
      damage frequency and damage index in hippocampus, striatum, cerebral cortex and
      blood when compared to control group. In conclusion, the present work
      demonstrated that DNA damage can be encountered in brain from animal models of
      hypertyrosinemia, DNA alterations may represent a further means to explain
      neurological dysfunction in this inherited metabolic disorder and to reinforce
      the role of oxidative stress in the pathophysiology of tyrosinemia type II.

PMID- 24297754
TI  - Pacemaker pocket displacement as a symptom of lead dependent infective
      endocarditis.
AB  - We here present a case of lead dependent infective endocarditis which manifested
      with pacemaker pocket displacement to the left infra mammary region. The patient
      underwent pacemaker removal without its reimplantation. 

PMID- 24297752
TI  - Multiple mechanisms determine ER network morphology during the cell cycle in
      Xenopus egg extracts.
AB  - In metazoans the endoplasmic reticulum (ER) changes during the cell cycle, with
      the nuclear envelope (NE) disassembling and reassembling during mitosis and the
      peripheral ER undergoing extensive remodeling. Here we address how ER morphology
      is generated during the cell cycle using crude and fractionated Xenopus laevis
      egg extracts. We show that in interphase the ER is concentrated at the
      microtubule (MT)-organizing center by dynein and is spread by outward extension
      of ER tubules through their association with plus ends of growing MTs. Fusion of
      membranes into an ER network is dependent on the guanosine triphosphatase
      atlastin (ATL). NE assembly requires fusion by both ATL and ER-soluble N-ethyl
      maleimide-sensitive factor adaptor protein receptors. In mitotic extracts, the ER
      converts into a network of sheets connected by ER tubules and loses most of its
      interactions with MTs. Together, these results indicate that fusion of ER
      membranes by ATL and interaction of ER with growing MT ends and dynein cooperate
      to generate distinct ER morphologies during the cell cycle. 

PMID- 24297755
TI  - [Atrio-ventricular block in the presence of double-chamber ICD--how is that
      possible?].
AB  - We present description of ECG by Holter monitoring in a 26-year-old patient with
      double-chamber implantable cardioverter-defibrillator (ICD). Fragments of record
      show atrio-ventricular block, which may suggests ICD dysfunction. However, this
      is working mode of ICD having minimal ventricular pacing algorhythm. 

PMID- 24297757
TI  - Exploring the genetic architecture of alcohol dependence in African-Americans via
      analysis of a genomewide set of common variants.
AB  - Alcohol dependence (AD) is a complex psychiatric disorder that affects about 12.5
      % of US adults. Genetic factors play a major role in the development of AD. We
      conducted a genomewide association study in 2,875 African-Americans including
      1,719 AD cases and 1,156 controls. We used the Illumina Omni 1-Quad microarray,
      which yielded 769,498 single-nucleotide polymorphisms (SNPs) after quality
      control. To explore the genetic architecture of AD, we estimated the variance
      that could be explained by all SNPs and subsets of SNPs using two different
      approaches to genome partitioning. We found that 23.9 % (s.e. 9.3 %) of the
      phenotypic variance could be explained by using all of the common SNPs on the
      array. We also found a significant linear relationship between the proportion of
      the top SNPs used and the phenotypic variance explained by them. Based on genome
      partitioning of common variants, we also observed a significant linear
      relationship between the variance explained by a chromosome and its length.
      Chromosome 4, known to contain several AD risk genes, accounted for excess risk
      in proportion to its length. By functional partitioning, we found that the
      genetic variants within 20 kb of genes explained 17.5 % (s.e. 11.4 %) of the
      phenotypic variance. Our findings are consistent with the generally accepted view
      that AD is a highly polygenic trait, i.e., the genetic risk in AD appears to be
      conferred by multiple variants, each of which may have a small or moderate
      effect. 

PMID- 24297756
TI  - Long nonoding RNAs in the X-inactivation center.
AB  - The X-inactivation center is a hotbed of functional long noncoding RNAs in
      eutherian mammals. These RNAs are thought to help orchestrate the epigenetic
      transcriptional states of the two X-chromosomes in females as well as of the
      single X-chromosome in males. To balance X-linked gene expression between the
      sexes, females undergo transcriptional silencing of most genes on one of the two
      X-chromosomes in a process termed X-chromosome inactivation. While one X
      chromosome is inactivated, the other X-chromosome remains active. Moreover, with
      a few notable exceptions, the originally established epigenetic transcriptional
      profiles of the two X-chromosomes is maintained as such through many rounds of
      cell division, essentially for the life of the organism. The stable and divergent
      transcriptional fates of the two X-chromosomes, despite residing in a shared
      nucleoplasm, make X-inactivation a paradigm of epigenetic transcriptional
      regulation. Originally proposed in 1961 by Mary Lyon, the X-inactivation
      hypothesis has been validated through much experimentation. In the last 25 years,
      the discovery and functional characterization has firmly established X-linked
      long noncoding RNAs as key players in choreographing X-chromosome inactivation.

PMID- 24297759
TI  - Factors associated with duration before receiving definitive diagnosis of
      narcolepsy among Japanese patients affected with the disorder.
AB  - BACKGROUND: Narcolepsy (NA) is a sleep disorder characterized by excessive
      daytime sleepiness and an increased propensity of rapid eye movement sleep. If
      left untreated, NA can lead to academic underachievement or job loss because of
      dozing off or mistakes caused by inattentiveness due to sleepiness. PURPOSE:
      Although untreated narcolepsy patients may suffer from many social disadvantages
      due to excessive daytime sleepiness, mostly it takes a long time to receive a
      definitive diagnosis of the disorder. This retrospective study investigated
      factors related to the period until definitive diagnosis among patients with
      narcolepsy in Japan. METHODS: We enrolled 181 consecutive patients (108 men, 73
      women; mean age 37.6 +/- 16.6 years old; narcolepsy with cataplexy/narcolepsy
      without cataplexy = 131:50). Multivariate logistic regression analysis was
      performed with period until definitive diagnosis as the dependent variable and
      descriptive clinical variables as the independent variables. RESULTS: The mean
      period until receiving the diagnosis among the participants was 9.9 +/- 10.1
      years. More than half of the patients first learned about the disorder from
      information provided by the media. Multivariate logistic analysis indicated that
      adult onset (p < 0.01), onset in 1995 or later (p < 0.001), and first learning
      about the disorder from a sleep disorder specialist physician or a general
      practitioner (p < 0.001) were associated with a time taken for receiving a
      definitive diagnosis less than or equal to the median value (7 years).
      CONCLUSION: Improving access to information about the concept of the disorder and
      the medical institutions specialized in sleep disorders, especially via the
      Internet, would be necessary to promote early diagnosis of the disorder.

PMID- 24297760
TI  - Dimensional or categorical approach to tinnitus severity: an item response
      mixture modeling analysis of tinnitus handicap.
AB  - BACKGROUND: Whether handicap due to tinnitus-sound(s) in the ears and/or in the
      head in the absence of an external auditory source-is best conceived as
      dimensional or categorical remains an unanswered empirical question. PURPOSE: The
      objective was to investigate whether tinnitus severity was best conceptualized as
      qualitatively distinct subtypes, quantitative differences varying along a single
      continuum, or as severity differences within subtypes. METHODS: Various forms of
      item response mixture models (latent class models, factor analysis models, and
      hybrid models) that corresponded to the competing hypotheses were fitted to item
      responses on the Tinnitus Handicap Inventory in a Swedish sample of individuals
      with tinnitus (N = 362). RESULTS: A latent class model could be fitted to the
      data with a high probability of correctly classifying individuals into three
      different classes: high-, moderate-, and low-severity classes. However, a
      comparison of models showed that a unidimensional factor analysis model with a
      single class provided the best fit to the data. CONCLUSIONS: The analysis
      provided evidence that tinnitus severity varies along a single severity continuum
      from mild to moderate to severe tinnitus-related handicap. The result that
      tinnitus severity exists on a continuum rather than as discrete categories has
      important implications for clinical research.

PMID- 24297761
TI  - Altered resting-state functional and white matter tract connectivity in stroke
      patients with dysphagia.
AB  - BACKGROUND: Swallowing dysfunction is intractable after acute stroke. Our
      understanding of the alterations in neural networks of patients with neurogenic
      dysphagia is still developing. OBJECTIVE: The aim was to investigate cerebral
      cortical functional connectivity and subcortical structural connectivity related
      to swallowing in unilateral hemispheric stroke patients with dysphagia. METHODS:
      We combined a resting-state functional connectivity with a white matter tract
      connectivity approach, recording 12 hemispheric stroke patients with dysphagia,
      12 hemispheric stroke patients without dysphagia, and 12 healthy controls.
      Comparisons of the patterns in swallowing-related functional connectivity maps
      between patient groups and control subjects included (a) seed-based functional
      connectivity maps calculated from the primary motor cortex (M1) and the
      supplementary motor area (SMA) to the entire brain, (b) a swallowing-related
      functional connectivity network calculated among 20 specific regions of interest
      (ROIs), and (c) structural connectivity described by the mean fractional
      anisotropy of fibers bound through the SMA and M1. RESULTS: Stroke patients with
      dysphagia exhibited dysfunctional connectivity mainly in the sensorimotor-insula
      putamen circuits based on seed-based analysis of the left and right M1 and SMA
      and decreased connectivity in the bilateral swallowing-related ROIs functional
      connectivity network. Additionally, white matter tract connectivity analysis
      revealed that the mean fractional anisotropy of the white matter tract was
      significantly reduced, especially in the left-to-right SMA and in the
      corticospinal tract. CONCLUSIONS: Our results indicate that dysphagia secondary
      to stroke is associated with disruptive functional and structural integrity in
      the large-scale brain networks involved in motor control, thus providing new
      insights into the neural remodeling associated with this disorder.

PMID- 24297762
TI  - Changes in white matter connectivity following therapy for anomia post stroke.
AB  - BACKGROUND: The majority of studies investigating the neural mechanisms
      underlying treatment-induced recovery in aphasia have focused on the cortical
      regions associated with language processing. However, the integrity of the white
      matter connecting these regions may also be crucial to understanding treatment
      mechanisms. OBJECTIVE: This study investigated the integrity of the arcuate
      fasciculus (AF) and uncinate fasciculus (UF) before and after treatment for
      anomia in people with aphasia. METHOD: Eight people with aphasia received 12
      treatment sessions to improve naming; alternating between phonologically-based
      and semantic-based tasks, with high angular resolution diffusion imaging
      conducted pre and post treatment. The mean generalized fractional anisotropy
      (GFA), a measure of fiber integrity, and number of fibers in the AF and UF were
      compared pre and post treatment, as well as with a group of 14 healthy older
      controls. RESULTS: Pre treatment, participants with aphasia had significantly
      fewer fibers and lower mean GFA in the left AF compared with controls. Post
      treatment, mean GFA increased in the left AF to be statistically equivalent to
      controls. Additionally, mean GFA in the left AF pre and post treatment positively
      correlated with maintenance of the phonologically based treatment. No differences
      were found in the right AF, or the UF in either hemisphere, between participants
      with aphasia and controls, and no changes were observed in these tracts following
      treatment. CONCLUSIONS: Anomia treatments may improve the integrity of the white
      matter connecting cortical language regions. These preliminary results add to the
      understanding of the mechanisms underlying treatment outcomes in people with
      aphasia post stroke.

PMID- 24297763
TI  - Robotic therapy provides a stimulus for upper limb motor recovery after stroke
      that is complementary to and distinct from conventional therapy.
AB  - BACKGROUND: Individuals with chronic stroke often have long-lasting upper
      extremity impairments that impede function during activities of daily living.
      Rehabilitation robotics have shown promise in improving arm function, but current
      systems do not allow realistic training of activities of daily living. We have
      incorporated the ARMin III and HandSOME device into a novel robotic therapy
      modality that provides functional training of reach and grasp tasks. OBJECTIVE:
      To compare the effects of equal doses of robotic and conventional therapy in
      individuals with chronic stroke. METHODS: Subjects were randomized to 12 hours of
      robotic or conventional therapy and then crossed over to the other therapy type
      after a 1-month washout period. Twelve moderate to severely impaired individuals
      with chronic stroke were enrolled, and 10 completed the study. RESULTS: Across
      the 3-month study period, subjects showed significant improvements in the Fugl
      Meyer (P = .013) and Box and Blocks tests (P = .028). The robotic intervention
      produced significantly greater improvements in the Action Research Arm Test than
      conventional therapy (P = .033). Gains in the Box and Blocks test from
      conventional therapy were larger than from robotic therapy in subjects who
      received conventional therapy after robotic therapy (P = .044). CONCLUSIONS: Data
      suggest that robotic therapy can elicit improvements in arm function that are
      distinct from conventional therapy and supplements conventional methods to
      improve outcomes. Results from this pilot study should be confirmed in a larger
      study.

PMID- 24297764
TI  - Substance abuse in emergency department patients with unexplained syncope.
AB  - Current data suggest that up to 60 % of patients presenting to the ED with
      syncope leave the hospital without a defined etiology. Although a relationship
      between syncope and substance abuse has been described, no study to date has
      looked at the relationship between syncope of unknown etiology and substance
      abuse in patients presenting to the ED. The objective of the study was to
      determine whether a history of or current substance abuse is associated with an
      increased incidence of syncope of unknown etiology in ED patients. A prospective,
      observational, cohort study of consecutive ED patients aged >=18 who presented
      with syncope was conducted between 6/03 and 7/06. Patients were queried in the ED
      and charts reviewed about a history of or current substance abuse. Substance
      abuse was defined as consumption of >2 alcoholic beverages nightly, repetitive
      use of any illicit substances, or documentation by the patient's physician of
      concern regarding suspected substance abuse. Data were analyzed using SAS with
      Chi-squared and Fisher's exact tests. We enrolled 518 patients who presented to
      the ED after syncope, 161 of whom did not have an identifiable etiology for their
      syncopal event. 62 patients had a history of, or current substance abuse. Among
      patients with a history of, or current substance abuse, 45 % had unexplained
      syncope, as opposed to 29 % of patients without such a history (p = 0.01). Our
      results suggest that prior and current substance abuse is associated with
      increased incidence of syncope of unknown etiology. Patients evaluated in the ED
      or even hospitalized with syncope of unknown etiology may benefit from substance
      abuse screening and possibly detoxification referral. 

PMID- 24297766
TI  - Mean platelet volume can be affected by many confounding factors in chronic
      periodontitis.

PMID- 24297765
TI  - Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage and measurement of biomarkers.
AB  - Cisternal irrigation with thrombolytic agents was used to prevent post-SAH
      vasospasm, but its role remained inconclusive. To verify effectiveness of
      papaverine (PPV) in preventing vasospasm, we studied relationship between
      inflammatory biologic markers and vasospasm. This prospective study included 121
      patients with clipped anterior circulation aneurysms that had ruptured, and 372
      control patients. Patients were divided into three groups according to cisternal
      irrigation method: simple drain, papaverine group, and urokinase (UK) group.
      Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV
      group showed similar incidence of vasospasm with UK group, but lower incidence
      than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly
      higher in the SAH group than in the control group. CSF and serum levels were more
      elevated on day 7 than day 3, and the degree of elevation were more marked when
      measured in the CSF than in the serum. However, there was no statistical
      difference between measured levels of ICAM-1 and VCAM-1, and vasospasm
      development. PPV cisternal irrigation was similarly effective as UK at preventing
      vasospasm. Although neither PPV nor UK irrigation could reduce the concentration
      of adhesion molecules compared with simple drain, we found levels of ICAM-1 and
      VCAM-1 were specifically elevated in the CSF. Therefore, further research should
      focus on anti-inflammation as a therapeutic target against cerebral vasospasm and
      on the CSF as the optimum place where such inflammatory action practically
      brought about.

PMID- 24297767
TI  - Association of strength of community service to personal wellbeing.
AB  - To assess the impact of community service on personal wellbeing in a mid-west
      church-based population. A prospective survey evaluating: self-reported community
      service, the perceived benefit of the service and its association to personal
      wellbeing. 309 participants were included of whom 92 % were employed full or part
      time, homemakers or students. Those who served in some capacity had better scores
      on five Wellbeing questions including: contentment, peace, joy, purpose and
      community acceptance (P < 0.02), but not better self-perceived mental or physical
      health (P > 0.05). People who served had a better combined Wellbeing score than
      those who could not serve (P = 0.03). A higher number of hours served/week was
      associated with better Global Wellbeing (P = 0.02). The greatest perceived
      benefit of service was related to enhancing wellbeing of others and the service
      organization itself (P < 0.0001). Church going adults, who are serving in some
      capacity in their church or community, may demonstrate heightened personal
      wellbeing compared to those who are not assisting others.

PMID- 24297768
TI  - Myectomy as an alternative solution for systolic anterior motion in a patient who
      underwent mitral valve repair.
AB  - Systolic anterior motion (SAM) of the mitral apparatus is a relatively frequent
      complication of mitral valve repair. When significant SAM persists despite
      intraoperative medical therapies, a second repair is generally required. We
      describe a rare case of SAM due to a hypertrophic septum in a patient who
      underwent mitral valve repair, with no preoperative obstruction of the left
      ventricular outflow tract. The present case of SAM was successfully treated only
      with transaortic septal myectomy. Therefore, myectomy might be considered as an
      alternative solution for SAM that is suspected to be caused by a hypertrophic
      septum after mitral valve repair. 

PMID- 24297769
TI  - WHO Framework Convention on Tobacco Control in China: barriers, challenges and
      recommendations.
AB  - AIM: The aim of this study was to analyze the barriers in the implementation of
      the Framework Convention on Tobacco Control (FCTC) in China and present
      recommendations on ways to address these challenges in tobacco control in China.
      METHODS: We review the available literature on progress and explore the barriers
      and challenges that impede a speedier pace in the adoption of the effective
      tobacco control measures, and present recommendations based on in-depth knowledge
      of decision-making process on the implementation of FCTC in China. RESULTS: The
      pace of progress in China is too slow. China faces intractable political,
      structural, economic and social barriers in tobacco control, which make the whole
      hearted implementation of FCTC measures a painstaking process. DISCUSSION: The
      authors recommend a comprehensive approach to speed up the implementation of
      tobacco control measures. This includes strong political leadership from the top,
      structural changes to the tobacco industry and government oversight of the
      tobacco industry, as well as advocacy and support for tobacco control from civil
      society at the grassroots level.

PMID- 24297770
TI  - Discrepant results from sampling different lumens of multilumen catheters: the
      case for sampling all lumens.
AB  - It is unclear whether blood culture samples should be obtained through one or
      multiple catheter lumens. We measured how frequently drawing blood cultures from
      all the lumens from a multilumen catheter resulted in discordant results and how
      often these caused medical interventions. We performed a retrospective review of
      the microbiology database of the National Institutes of Health (NIH) Clinical
      Center. Most patients were immunocompromised. All blood cultures obtained from
      May 1, 2007 to April 30, 2009 were reviewed. We analyzed all positive blood
      cultures (i.e., positivity of any of the blood cultures drawn through the
      catheter lumens) when simultaneous samples from different lumens were obtained,
      and reviewed the medical charts of those in which blood cultures from different
      lumens had discordant results (i.e., not all lumens revealed the same organism).
      We also analyzed how often the discordant results lead to a medical intervention,
      defined as a change of antimicrobials and/or removal of the catheter. There were
      405 episodes of positive blood cultures, in which simultaneous samples of
      different lumens of a multilumen catheter were obtained. Eighty-five episodes (21
      %) were considered to be contaminants and excluded. We analyzed 320 episodes of
      positive blood cultures in 153 patients; 173 episodes (54.1 %) had discordant
      results. In 77 % of the 173 episodes, the discordant isolate led to a medical
      intervention. In immunocompromised patients, sampling all the lumens of a
      multilumen catheter results in more positive blood cultures, and many of these
      result in medical interventions. When evaluating bloodstream infection in
      patients with multilumen catheters, sampling all lumens should be strongly
      considered.

PMID- 24297771
TI  - Late percutaneous coronary intervention for an occluded infarct-related artery in
      patients with preserved infarct zone viability: a pooled analysis of
      cardiovascular magnetic resonance studies.
AB  - BACKGROUND: The results of clinical trials assessing the effect of late opening
      of infarct-related artery (IRA) on left ventricular ejection fraction (LVEF) and
      size in stable patients are equivocal, which may be related to the fact that the
      presence of viability was not a requirement for randomization in these trials.
      The aim of the study was to assess the influence of late percutaneous coronary
      intervention (PCI) with optimal medical therapy (OMT) vs. OMT alone on cardiac
      function and remodeling in patients presenting infarct zone with preserved
      viability on cardiovascular magnetic resonance (CMR). METHODS: The analysis
      included pooled data of 43 patients from 3 randomized studies. All patients
      underwent CMR before randomization, but only in 1 previously unpublished study
      was preserved viability required for randomization to treatment. Follow-up CMR
      was performed after 6-12 months. RESULTS: Late PCI with OMT led to improved LVEF
      (+5 +/- 7% vs. -1 +/- 6%, p = 0.005), decreased left ventricular end-systolic
      volume (-11 +/- 19 mL vs. 12 +/- 40 mL, p = 0.02) and a trend towards a decrease
      in end-diastolic volume (-7 +/- 27 mL vs. 15 +/- 47 mL, p = 0.07) in comparison
      to OMT alone. Increased LVEF and decreased left ventricular volumes were observed
      after the analysis was restricted to patients with left anterior descending
      artery (LAD) occlusion. CONCLUSIONS: In patients with the presence of infarct
      zone viability, OMT with late PCI for an occluded IRA (particularly LAD) is
      associated with improvement of left ventricular systolic function and size over
      OMT alone.

PMID- 24297773
TI  - The effect of insert conformity and material on total knee replacement wear.
AB  - The mean average life is increasing; therefore, there is a need to increase the
      lifetime of the prostheses. To fulfil this requirement, new prosthetic designs
      and materials are being introduced. Two of the design parameters that may affect
      wear of total knee replacements, and hence the expected lifetime, are the insert
      conformity and material. Computational models have been used extensively for wear
      prediction and optimisation of artificial knee designs. The objective of the
      present study was to use a previously validated non-dimensional wear coefficient
      based computational wear model to investigate the effect of insert conformity and
      material on the predicted wear in total knee replacements. Four different inserts
      (curved, lipped, partial flat and custom flat), with different conformity levels,
      were tested against the same femoral and under two different kinematic inputs
      (intermediate and high), with different levels of cross-shear. The insert bearing
      materials were either conventional or moderately cross-linked ultra-high
      molecular weight polyethylene (UHMWPE). Wear predictions were validated against
      the experimental data from Leeds knee simulation tests. The predicted wear rates
      for the curved insert (most conformed) were more than three times those for the
      flat insert (least conformed). In addition, the computationally predicted average
      volumetric wear rates for moderately cross-linked UHMWPE bearings were less than
      half of their corresponding conventional UHMWPE bearings. Moreover, the wear of
      the moderately cross-linked UHMWPE was shown to be less dependent on the degree
      of cross-shear, compared to conventional UHMWPE. These results along with
      supporting experimental studies provide insight into the design variables, which
      may reduce wear in knee replacements. 

PMID- 24297774
TI  - Iloprost reduces myocardial edema in a rat model of myocardial ischemia
      reperfusion.
AB  - OBJECTIVE: Myocardial ischemia severely reduces myocyte longevity and function.
      Extensive interstitial edema and cell damage occur as a result of myocardial
      reperfusion injury. Current therapies are directed at prevention of ischemia
      induced damage to cardiac tissue. Iloprost is a novel pharmaceutical agent for
      the treatment of ischemia. METHODS: Twenty rats were segregated into four
      experimental groups. The procedure control group consisted of four rats
      undergoing a sham operation. The remaining 16 rats were divided into two equal
      groups. The first group (control group) received a continuous intravenous
      infusion of physiological serum immediately prior to the procedure. Iloprost was
      administered by a continuous intravenous infusion into the right jugular vein at
      an infusion rate of 100 ng/kg/min for 30 minutes prior to reperfusion in the
      experimental group (study group). Following the infusion treatments, ligation of
      the left coronary artery was conducted for 30 minutes to induce myocardial
      ischemia. The rats were euthanized 24 hours after reperfusion and cardiac tissue
      was harvested from all specimens for analysis. RESULTS: Histological examination
      revealed three myocardial tissue specimens with grade II damage and five
      myocardial tissue specimens with grade III reperfusion injury in the control
      group. However, the study group consisted of two grade III myocardial tissue
      specimens, five grade II myocardial tissue specimens and one grade I myocardial
      tissue specimen. Moreover, a statistically significant reduction in myocardial
      edema was observed in the study group (p=0.022). CONCLUSION: Our results support
      the hypothesis that iloprost enhances protection against cardiac ischemia
      reperfusion injury. This protective effect may be associated with vasodilation,
      antioxidant or anti-edema mechanisms.

PMID- 24297775
TI  - The dichoptiscope: an instrument for investigating cues to motion in depth.
AB  - A stereoscope displays 2-D images with binocular disparities (stereograms), which
      fuse to form a 3-D stereoscopic object. But a stereoscopic object creates a
      conflict between vergence and accommodation. Also, motion in depth of a
      stereoscopic object simulated solely from change in target vergence produces
      anomalous motion parallax and anomalous changes in perspective. We describe a new
      instrument, which overcomes these problems. We call it the dichoptiscope. It
      resembles a mirror stereoscope, but instead of stereograms, it displays identical
      2-D or 3-D physical objects to each eye. When a pair of the physical, monocular
      objects is fused, they create a dichoptic object that is visually identical to a
      real object. There is no conflict between vergence and accommodation, and motion
      parallax is normal. When the monocular objects move in real depth, the dichoptic
      object also moves in depth. The instrument allows the experimenter to control
      independently each of several cues to motion in depth. These cues include changes
      in the size of the images, changes in the vergence of the eyes, changes in
      binocular disparity within the moving object, and changes in the relative
      disparity between the moving object and a stationary object. 

PMID- 24297776
TI  - Generative constraints on image cues for perceived gloss.
AB  - Image structure is generated by distinct physical sources that include 3-D
      surface geometry, surface reflectance, and the light field. A fundamental problem
      in midlevel vision involves understanding how, and how well, the visual system
      separates images into their underlying sources. A large body of recent work has
      shown that the perception of gloss exhibits significant dependencies on both 3-D
      surface geometry and the light field in which the surface is embedded. We
      recently proposed that these dependencies arise from the visual system relying on
      a restricted set of dimensions of specular image structure that are heuristically
      used to estimate surface gloss (Marlow, Kim, & Anderson, 2012). Here, we report a
      series of studies that manipulate surface geometry and the structure of the light
      field to prospectively test whether these image cues predict perceived gloss for
      a broad range of surface geometries and light fields. We identify generative
      constraints on each of our proposed cues that allow us to predict which cue will
      vary most for a given surface geometry, reflectance function, and light field.
      Our psychophysical data reveal that our generative manipulations succeed in
      promoting the significance of the intended cue, which in turn increases their
      predictive value in observers' judgments of gloss. Our results suggest that the
      perception of gloss in static, monocular images relies on a heuristic weighting
      of cues to specular image structure, and offer a unified explanation of why
      surface geometry and the light field modulate perceived gloss. 

PMID- 24297777
TI  - "Top-down" effects where none should be found: the El Greco fallacy in perception
      research.
AB  - A tidal wave of recent research purports to have discovered that higher-level
      states such as moods, action capabilities, and categorical knowledge can
      literally and directly affect how things look. Are these truly effects on
      perception, or might some instead reflect influences on judgment, memory, or
      response bias? Here, we exploited an infamous art-historical reasoning error (the
      so-called "El Greco fallacy") to demonstrate that multiple alleged top-down
      effects (including effects of morality on lightness perception and effects of
      action capabilities on spatial perception) cannot truly be effects on perception.
      We suggest that this error may also contaminate several other varieties of top
      down effects and that this discovery has implications for debates over the
      continuity (or lack thereof) of perception and cognition. 

PMID- 24297778
TI  - Prevalence effects in newly trained airport checkpoint screeners: trained
      observers miss rare targets, too.
AB  - Many socially important search tasks are characterized by low target prevalence,
      meaning that targets are rarely encountered. For example, transportation security
      officers (TSOs) at airport checkpoints encounter very few actual threats in carry
      on bags. In laboratory-based visual search experiments, low prevalence reduces
      the probability of detecting targets (Wolfe, Horowitz, & Kenner, 2005). In the
      lab, this "prevalence effect" is caused by changes in decision and response
      criteria (Wolfe & Van Wert, 2010) and can be mitigated by presenting a burst of
      high-prevalence search with feedback (Wolfe et al., 2007). The goal of this study
      was to see if these effects could be replicated in the field with TSOs. A total
      of 125 newly trained TSOs participated in one of two experiments as part of their
      final evaluation following training. They searched for threats in simulated bags
      across five blocks. The first three blocks were low prevalence (target prevalence
      <= .05) with no feedback; the fourth block was high prevalence (.50) with full
      feedback; and the final block was, again, low prevalence. We found that newly
      trained TSOs were better at detecting targets at high compared to low prevalence,
      replicating the prevalence effect. Furthermore, performance was better (and
      response criterion was more "liberal") in the low-prevalence block that took
      place after the high-prevalence block than in the initial three low-prevalence
      blocks, suggesting that a burst of high-prevalence trials may help alleviate the
      prevalence effect in the field. 

PMID- 24297780
TI  - External-cause mortality among adolescents and young adults in Greece over the
      millennium's first decade 2000-09.
AB  - BACKGROUND: Several important socio-behavioral public health problems that either
      peak or start during the second decade of life contribute to young people's
      mortality. The aim of this study was to explore patterns, rates, trends and
      regional variations of external-cause (due to environmental events/circumstances)
      mortality among young people aged 10-24 years in Greece, over the decade 2000-09.
      METHODS: Data were electronically derived from the database of the Hellenic
      Statistical Authority to study general and specific mortality rates by major
      causes of death. RESULTS: Road traffic crashes (RTCs), illicit drug use and
      suicide accounted for 65.8, 14.7 and 4.8%, of total external-cause mortality,
      respectively. Mortality rates (deaths per 100 000) did not exhibit intra-country
      variability, were higher in young adults than in adolescents, in males than in
      females and decreased by 39%, from 33.6 in 2000 to 20.4 in 2009 (P < 0.001), due
      to declines in mortality from RTCs (from 21.3 to 14.3; P = 0.001), substance
      abuse (from 5.1 to 2.1; P = 0.003) and suicides (from 2.0 to 0.9; P = 0.003).
      CONCLUSIONS: External causes of young people's mortality were mainly psychosocial
      and behavioral in origin. Despite improvement over the decade, young people in
      Greece still have unmet health-care needs and may further benefit from a
      multipronged public health approach through improved youth-friendly health
      services.

PMID- 24297781
TI  - Biomechanics-machine learning system for surgical gesture analysis and
      development of technologies for minimal access surgery.
AB  - BACKGROUND: The uptake of minimal access surgery (MAS) has by virtue of its
      clinical benefits become widespread across the surgical specialties. However,
      despite its advantages in reducing traumatic insult to the patient, it imposes
      significant ergonomic restriction on the operating surgeons who require training
      for the safe execution. Recent progress in manipulator technologies (robotic or
      mechanical) have certainly reduced the level of difficulty, however it requires
      information for a complete gesture analysis of surgical performance. This article
      reports on the development and evaluation of such a system capable of full
      biomechanical and machine learning. METHODS: The system for gesture analysis
      comprises 5 principal modules, which permit synchronous acquisition of multimodal
      surgical gesture signals from different sources and settings. The acquired
      signals are used to perform a biomechanical analysis for investigation of
      kinematics, dynamics, and muscle parameters of surgical gestures and a machine
      learning model for segmentation and recognition of principal phases of surgical
      gesture. RESULTS: The biomechanical system is able to estimate the level of
      expertise of subjects and the ergonomics in using different instruments. The
      machine learning approach is able to ascertain the level of expertise of subjects
      and has the potential for automatic recognition of surgical gesture for surgeon
      robot interactions. CONCLUSIONS: Preliminary tests have confirmed the efficacy of
      the system for surgical gesture analysis, providing an objective evaluation of
      progress during training of surgeons in their acquisition of proficiency in MAS
      approach and highlighting useful information for the design and evaluation of
      master-slave manipulator systems.

PMID- 24297779
TI  - Absence of P-glycoprotein transport in the pharmacokinetics and toxicity of the
      herbicide paraquat.
AB  - Genetic variation in the multidrug resistance gene ABCB1, which encodes the
      efflux transporter P-glycoprotein (P-gp), has been associated with Parkinson
      disease. Our goal was to investigate P-gp transport of paraquat, a Parkinson
      associated neurotoxicant. We used in vitro transport models of ATPase activity,
      xenobiotic-induced cytotoxicity, transepithelial permeability, and rhodamine-123
      inhibition. We also measured paraquat pharmacokinetics and brain distribution in
      Friend leukemia virus B-type (FVB) wild-type and P-gp-deficient (mdr1a(-/
      )/mdr1b(-/-)) mice following 10, 25, 50, and 100 mg/kg oral doses. In vitro data
      showed that: 1) paraquat failed to stimulate ATPase activity; 2) resistance to
      paraquat-induced cytotoxicity was unchanged in P-gp-expressing cells in the
      absence or presence of P-gp inhibitors GF120918 [N-(4-[2-(1,2,3,4-tetrahydro-6,7
      dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine
      carboxamide] and verapamil-37.0 [95% confidence interval (CI): 33.2-41.4], 46.2
      (42.5-50.2), and 34.1 uM (31.2-37.2)-respectively; 3) transepithelial
      permeability ratios of paraquat were the same in P-gp-expressing and
      nonexpressing cells (1.55 +/- 0.39 and 1.39 +/- 0.43, respectively); and 4)
      paraquat did not inhibit rhodamine-123 transport. Population pharmacokinetic
      modeling revealed minor differences between FVB wild-type and mdr1a(-/-)/mdr1b(-/
      ) mice: clearances of 0.47 [95% confidence interval (CI): 0.42-0.52] and 0.78 l/h
      (0.58-0.98), respectively, and volume of distributions of 1.77 (95% CI: 1.50
      2.04) and 3.36 liters (2.39-4.33), respectively; however, the change in clearance
      was in the opposite direction of what would be expected. It is noteworthy that
      paraquat brain-to-plasma partitioning ratios and total brain accumulation were
      the same across doses between FVB wild-type and mdr1a(-/-)/mdr1b(-/-) mice. These
      studies indicate that paraquat is not a P-gp substrate. Therefore, the
      association between ABCB1 pharmacogenomics and Parkinson disease is not
      attributed to alterations in paraquat transport. 

PMID- 24297782
TI  - An analysis of skills acquisition during a training program for experienced
      laparoscopists in laparoendoscopic single-site surgery.
AB  - BACKGROUND: Laparoendoscopic single-site surgery has been presented in the past
      few years as an innovative minimally invasive approach, one which despite its
      advantages is also challenging and requires specific training. We propose to
      analyze the performance of attendants in a specific LESS training course.
      METHODS: Following the LESSCAR 2010 guidelines, we focused on level 1 hands-on
      simulator tasks and level 2 hands-on training on animal model for skills
      acquisition during a LESS-specific training course. Each attendant completed
      coordination and cut tasks on simulator, followed by a cholecystectomy on an ex
      vivo porcine liver. Hands-on animal model each trainee performed 1
      cholecystectomy and at least 2 nephrectomies (N1, N2). Performance was analyzed
      through video recording and reviewed by 3 independent observers. Each result was
      registered according to a modified objective structured assessment of technical
      skills. Total task or procedure completion time was also determined. RESULTS:
      Regarding coordination and cut tasks, attendants improved on their performance
      from first to third attempts with an accompanying decrease in completion time.
      Surgeons completed the cholecystectomy on animal model significantly faster than
      on simulator, although with lower performance quality. Regarding N1 and N2,
      attendants showed improvement both in quality and total completion time.
      CONCLUSIONS: A gradual and positive evolution of attendants was observed
      throughout the training course. Thus, we believe a structured program for the
      acquisition of basic skills in new minimally invasive surgical approaches should
      be recommended. Considering that this is a small study, it would be advisable to
      increase the number of study subjects on future opportunities.

PMID- 24297783
TI  - Translating neuroimaging findings into psychiatric practice.
AB  - Although translational medicine has become a priority for medical science,
      advances in neuroscience have failed to be translated for the benefit of
      patients. In populations at high risk of psychosis, neuroimaging could stratify
      those mostly likely to develop psychosis. This is an example of potentially
      translatable psychiatry. 

PMID- 24297784
TI  - Neurology in the German training system for psychiatrists - a personal view.
AB  - In mid-19th-century Germany the conviction that 'mental disease is brain disease'
      was accompanied by a call for social reform in psychiatry. During neurology
      training, future psychiatrists often encounter patients with mental disorders
      rarely seen in psychiatric departments and learn how to avoid misdiagnosing brain
      diseases as mental disorders. 

PMID- 24297785
TI  - Treating anxiety in early life.
AB  - Anxiety disorders in pre-adolescence are probably the most common serious
      disorder of childhood, affecting around 1 in 30 British children. These
      conditions are chronic, distressing and impairing, and are treatable, but we are
      currently doing a poor job of serving these children. 

PMID- 24297786
TI  - Varieties of decisional incapacity: theory and practice.
AB  - Evaluation of decision-making capacity (DMC) for treatment is challenging. Owen
      et al, in this issue of the Journal, compare the abilities (understanding,
      appreciation and reasoning) relevant to DMC in medical and psychiatric patients.
      Here I discuss three key issues their article raises and that are relevant to the
      direction of future research. 

PMID- 24297787
TI  - Community treatment orders: current evidence and the implications.
AB  - Community treatment orders (CTOs) have been widely introduced to address the
      problems faced by 'revolving door' patients. A number of case-control studies
      have been conducted but show conflicting results concerning the effectiveness of
      CTOs. The Oxford Community Treatment Order Evaluation Trial (OCTET) is the third
      randomised controlled trial (RCT) to show that CTOs do not reduce rates of
      readmission over 12 months, despite restricting patients' autonomy. This evidence
      gives pause for thought about current CTO practice. Further high-quality RCTs may
      settle the contentious debate about effectiveness. 

PMID- 24297789
TI  - Exploring and addressing the unmet healthcare needs of Indian adolescents.

PMID- 24297788
TI  - Suicide by occupation: systematic review and meta-analysis.
AB  - BACKGROUND: Previous research has shown that those employed in certain
      occupations, such as doctors and farmers, have an elevated risk of suicide, yet
      little research has sought to synthesise these findings across working-age
      populations. AIMS: To summarise published research in this area through
      systematic review and meta-analysis. METHOD: Random effects meta-analyses were
      used to calculate a pooled risk of suicide across occupational skill-level
      groups. RESULTS: Thirty-four studies were included in the meta-analysis.
      Elementary professions (e.g. labourers and cleaners) were at elevated risk
      compared with the working-age population (rate ratio (RR) = 1.84, 95% CI 1.46
      2.33), followed by machine operators and deck crew (RR = 1.78, 95% CI 1.22-2.60)
      and agricultural workers (RR = 1.64, 95% CI 1.19-2.28). Results suggested a
      stepwise gradient in risk, with the lowest skilled occupations being at greater
      risk of suicide than the highest skill-level group. CONCLUSIONS: This is the
      first comprehensive meta-analytical review of suicide and occupation. There is a
      need for future studies to investigate explanations for the observed skill-level
      differences, particularly in people employed in lower skill-level groups.

PMID- 24297790
TI  - Authors' reply.

PMID- 24297791
TI  - RNA sequencing identifies multiple fusion transcripts, differentially expressed
      genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs
      BRAF wild-type papillary thyroid carcinoma.
AB  - CONTEXT: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in
      papillary thyroid carcinoma, but unidentified additional genomic abnormalities
      may be required for full phenotypic expression. OBJECTIVE: RNA sequencing (RNA
      Seq) was performed to identify genes differentially expressed between BRAF-MUT
      and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical
      status. DESIGN: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0
      and T2-3N1 tumors evaluated in a referral medical center. Gene expression levels
      were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed
      capture/detection and digital counting of mRNA transcripts (nCounter, NanoString
      Technologies) validated RNA-Seq data for immune system-related genes. PATIENTS:
      BRAF-MUT patients included nine women, three men; nine were TNM stage I and three
      were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included
      five women, three men; all were stage I, and five (62.5%) had tumor infiltrating
      lymphocytes. RESULTS: RNA-Seq identified 560 of 13 085 genes differentially
      expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes
      were related to MetaCore immune function pathways; 51 were underexpressed in BRAF
      MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four
      most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19;
      CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA
      Seq expression level data. Eleven different high-confidence fusion transcripts
      were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors.
      All in-frame fusions were validated by RT-PCR. CONCLUSION: BRAF-MUT papillary
      thyroid cancers have reduced expression of immune/inflammatory response genes
      compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In
      contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five
      percent of tumors had between one and three fusion transcripts. Functional
      studies will be required to determine the potential role of these newly
      identified genomic abnormalities in contributing to the aggressiveness of BRAF
      MUT and BRAF-WT tumors.

PMID- 24297793
TI  - The response to gonadotropin releasing hormone (GnRH) stimulation test does not
      predict the progression to true precocious puberty in girls with onset of
      premature thelarche in the first three years of life.
AB  - CONTEXT: Premature thelarche in early childhood may evolve into true precocious
      puberty. The individuation of cases progressing to precocious puberty is
      challenging. OBJECTIVE: We analyzed the parameters predictive for progression in
      girls younger than 3 years. DESIGN AND SETTING: We conducted a retrospective
      longitudinal study. PATIENTS AND METHODS: A total of 450 girls referred for
      premature thelarche were initially evaluated, 353 were clinically monitored at 3
      month intervals, and 97 underwent endocrine and imaging assessment. Central
      precocious puberty (CPP) was diagnosed in girls showing LH peak response to GnRH
      testing >5 mU/mL with tuber cinereum hamartoma at magnetic resonance imaging, or
      with normal magnetic resonance imaging but progression of puberty during follow
      up. MAIN OUTCOME MEASURE: We measured the progression to precocious puberty.
      RESULTS: Idiopathic premature thelarche (IPT) was diagnosed in 85 of the 97 girls
      who underwent extensive evaluation, CPP in nine girls, and peripheral precocious
      puberty in three girls. The uterus was >34 mm in six (7%) IPT girls and six
      (66.6%) CPP girls. Basal LH was >0.2 mU/mL in one (1.17%) IPT girl and eight
      (88.8%) CPP girls. LH peak was >5 mU/mL in 31 (36.4%) IPT girls and nine (100%)
      CPP girls. LH peak/FSH peak ratio was >1 in six (66.6%) CPP girls. CONCLUSIONS:
      None of the available tests alone allows identification of girls who will
      progress to precocious puberty. Elevated LH responses to GnRH are common but are
      not related to progression toward puberty. The combined measurement of basal LH
      and longitudinal diameter of the uterus represents a reliable screening approach
      to identify subjects who should undergo GnRH testing.

PMID- 24297792
TI  - Carbohydrate feeding dissociates the postprandial FGF19 response from circulating
      bile acid levels in humans.
AB  - CONTEXT: Fibroblast growth factor 19 (FGF19) improves glycemic control in
      diabetic animals and is secreted from the gastrointestinal tract after meals in
      response to bile acid stimulation. OBJECTIVE: We sought to understand how
      ingestion of carbohydrates, protein or lipids affect both FGF19 and bile acid
      concentrations in human plasma, with the hypothesis that variation in the bile
      acid response to different macronutrients would predict differences in plasma
      FGF19 levels. DESIGN: This was a randomized, within-subjects crossover study.
      SETTING: The study was conducted at a university clinical research center.
      PARTICIPANTS: There were 16 healthy human subjects included in the study.
      INTERVENTIONS: Isocaloric, isovolemic beverages composed primarily of
      carbohydrates, proteins, or lipids were provided to each participant on 3
      separate occasions. MAIN OUTCOME MEASURES: The magnitudes of postprandial rises
      of plasma FGF19 and total bile acid levels were determined. RESULTS: All
      beverages induced an initial transient decline of plasma FGF19 levels during the
      first 60 minutes after consumption. For FGF19, the ingestion of carbohydrate was
      associated with the fastest and highest increase of plasma levels, returning to
      baseline at 5 hours. By comparison, the protein beverage induced a modest but
      significant elevation of FGF19 levels that peaked at the end of the 6-hour
      sampling interval, whereas a lipid beverage was without effect. In contrast,
      total bile acid levels increased in plasma only in response to a high-lipid
      beverage, demonstrating a marked divergence between the FGF19 and bile acid
      response to lipid vs carbohydrate. CONCLUSIONS: A bile acid-independent mechanism
      is implicated in the effect of meals to raise plasma FGF19 concentrations.

PMID- 24297794
TI  - Tumor(s) induced osteomalacia--a curious case of double trouble.
AB  - CONTEXT: We report a case of tumor-induced osteomalacia with evidence of
      synchronous multifocal fibroblast growth factor 23 (FGF23) production. OBJECTIVE:
      The aim is to present a case of tumor-induced osteomalacia and to highlight the
      fact that incomplete removal of multifocal FGF23-producing tumors, which are not
      entirely picked up by functional imaging, could be the cause of treatment
      failure. SETTING: The patient was treated in the Department of Endocrinology of a
      tertiary care center in India. PATIENT: We report the case of a 42-year-old male
      with tumor-induced osteomalacia. INTERVENTION: We treated the tumor-induced
      osteomalacia with staged surgery of the two tumors. The 18F-fluorodeoxyglucose
      (FDG)-avid lesion (considered the sole culprit lesion after functional imaging)
      was resected first, followed by the non-FDG-avid lesion. The sequential removal
      of both tumors resulted in complete cure. RESULTS: The patient had
      hypophosphatemia and hyperphosphaturia. C-Terminal FGF23 level was elevated.
      Positron emission tomography-computed tomography showed two lesions-an FDG-avid
      lesion in the right leg, and a non-avid lesion in the left thigh. After removal
      of the FDG-avid lesion, the hypophosphatemia persisted, and the FGF23 level
      showed only modest reduction. The patient had complete clinical and biochemical
      resolution only after removal of the second non-FDG-avid tumor. CONCLUSIONS: We
      present the case of a tumor-induced osteomalacia whose biochemical parameters did
      not improve after removal of the FDG-avid tumor initially. The possibility of
      multifocal FGF23 production was considered, and the second, non-FDG-avid lesion
      was resected, which resulted in complete cure. Thorough clinical examination and
      meticulous follow-up with documentation of the biochemical resolution are
      necessary for management of all patients with this rare disorder.

PMID- 24297795
TI  - Oncostatin m is produced in adipose tissue and is regulated in conditions of
      obesity and type 2 diabetes.
AB  - CONTEXT: Adipose tissue is a highly active endocrine organ that secretes many
      factors that affect other tissues and whole-body metabolism. Adipocytes are
      responsive to several glycoprotein 130 (gp130) cytokines, some of which have been
      targeted as potential antiobesity therapeutics. OBJECTIVE: Oncostatin M (OSM) is
      a gp130 family member known to inhibit adipocyte differentiation in vitro, but
      its effects on other adipocyte properties are not characterized. The expression
      of OSM in white adipose tissue (WAT) has not been evaluated in the context of
      obesity. Thus, our objective was to examine the expression of adipose tissue OSM
      in obese animals and humans. DESIGN: OSM expression was examined in adipose
      tissues from mice with diet-induced and genetic obesity and in obese humans as
      well as in fractionated adipose tissue from mice. Murine adipocytes were used to
      examine OSM receptor expression and the effects of OSM on adipocytes, including
      the secretion of factors such as plasminogen activator inhibitor 1 and IL-6,
      which are implicated in metabolic diseases. RESULTS: OSM expression is increased
      in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels
      correlate with body weight and insulin and are inversely correlated with glucose
      disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not
      produced from the adipocytes in WAT but derives from cells in the stromovascular
      fraction, including F4/80(+) macrophages. The specific receptor of OSM, OSM
      receptor-beta, is expressed in adipocytes and adipose tissue and increased in
      both rodent models of obesity examined. OSM acts on adipocytes to induce the
      expression and secretion of plasminogen activator inhibitor 1 and IL-6.
      CONCLUSIONS: These data indicate that WAT macrophages are a source of OSM and
      that OSM levels are significantly induced in murine and human obesity/type 2
      diabetes mellitus. These studies suggest that OSM produced from immune cells in
      WAT acts in a paracrine manner on adipocytes to promote a proinflammatory
      phenotype in adipose tissue.

PMID- 24297796
TI  - Intrafollicular endocrine milieu after addition of hCG to recombinant FSH during
      controlled ovarian stimulation for in vitro fertilization.
AB  - CONTEXT: The role of human chorionic gonadotropin (hCG) supplementation on the
      intrafollicular steroid milieu has been studied. OBJECTIVE: The objective of the
      study was to assess the impact on steroid levels in follicular fluids (FFs) after
      different doses of hCG supplementation to recombinant FSH for controlled ovarian
      stimulation. SETTING: This was a prospective randomized dose-response study
      conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. PATIENTS:
      From 62 in vitro fertilization patients, 334 FFs were selected for analyses.
      INTERVENTIONS: Patients were treated using a GnRH agonist protocol with
      recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation
      with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d. MAIN
      OUTCOME MEASURE: Intrafollicular hormone concentrations in relation to treatment
      groups, follicular sizes, and embryo quality were measured. RESULTS: In large
      follicles, hCG supplementation induced a nearly 3-fold increase of estradiol
      (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P < .001)], a
      significant 3-fold increase of androstenedione, and a 5-fold increase of T
      (nanomoles per liter) [D0: 15; D50: 38; D100: 72; D150: 56 (P < .001)]. The
      estradiol to T ratio decreased significantly, with the lowest ratio in D100 and
      the highest in D0. Large follicles giving rise to good-quality embryos had
      significantly higher estradiol and progesterone levels and estradiol to T,
      estradiol to androstenedione, and progesterone to estradiol ratios, compared with
      small follicles, leading to poor-quality embryos. CONCLUSIONS: Increasing doses
      of hCG supplementation markedly stimulated the intrafollicular concentration of
      both estradiol and androgens, with a shift toward a more androgenic milieu. In
      large follicles with oocytes giving rise to good-quality embryos, the FFs were
      significantly more estrogenic than in small follicles with oocytes developing
      into poor quality embryos.

PMID- 24297797
TI  - HbA1c and heart failure risk among diabetic patients.
AB  - CONTEXT: Diabetes is an independent risk factor for heart failure (HF); however,
      it is not known whether tight glycemic control can reduce the occurrence of HF
      among diabetic patients. OBJECTIVE: The aim of the study was to investigate the
      race-specific association of different levels of glycosylated hemoglobin (HbA1c)
      with the risk of HF among patients with diabetes. DESIGN, SETTING, AND
      PARTICIPANTS: We prospectively investigated the race-specific association of
      different levels of HbA1c at baseline and during an average of 6.5 years of
      follow-up with incident HF risk among 17 181 African American and 12 446 white
      diabetic patients within the Louisiana State University Hospital System. MAIN
      OUTCOME MEASURE: We measured incident HF until May 31, 2012. RESULTS: During
      follow-up, 5089 HF incident cases were identified. The multivariable-adjusted
      hazard ratios of HF associated with different levels of HbA1c at baseline (<6.0%
      [reference group], 6.0-6.9%, 7.0-7.9%, 8.0-8.9%, 9.0-9.9%, and >=10.0%,) were
      1.00, 1.02 (95% confidence interval, 0.91-1.15), 1.21 (1.05-1.38), 1.29 (1.12
      1.50), 1.37 (1.17-1.61), and 1.49 (1.31-1.69) (P trend < .001) for African
      American diabetic patients, and 1.00, 1.09 (0.96-1.22), 1.09 (0.95-1.26), 1.43
      (1.22-1.67), 1.49 (1.25-1.77), and 1.61 (1.38-1.87) (P trend < .001) for white
      diabetic patients, respectively. This graded positive association was also
      present in diabetic patients with and without glucose-lowering agent treatment;
      in diabetic patients with different age, gender, and smoking status; and in
      incident HF defined as systolic HF (ejection fraction <= 40%) and HF with a
      preserved ejection fraction (ejection fraction > 40%). CONCLUSIONS: The current
      study suggests a graded positive association of HbA1c with the risk of HF among
      both African American and white patients with diabetes.

PMID- 24297798
TI  - Progression of medullary thyroid cancer in RET carriers of ATA class A and C
      mutations.
AB  - CONTEXT: There is no histopathological or radiological information on the natural
      course of tumor growth and lymph node metastasis in medullary thyroid cancer
      (MTC). OBJECTIVE: This investigation aimed at determining annual rates of tumor
      growth and lymph node metastasis in hereditary MTC at the surgical pathology
      level. DESIGN: This was a retrospective analysis. SETTING: The setting was a
      tertiary referral center. PATIENTS: Included were 172 carriers of American
      Thyroid Association (ATA) class C (95 patients) and class A rearranged during
      transfection (RET) mutations (77 patients) with MTC. INTERVENTION: The
      intervention was compartment-oriented surgery. MAIN OUTCOME MEASURES: Comparisons
      of means between index and nonindex patients yielded incremental primary tumor
      diameter and incremental number of lymph node metastases, which were divided by
      incremental patient age at tissue diagnosis. RESULTS: Annual primary tumor growth
      was 0.4-0.5 mm in node-negative carriers of ATA class A and C mutations. In node
      positive carriers, annual primary tumor growth was 2.6 mm (ATA class C mutations)
      and 1.2 mm (ATA class A mutations), more than 6-fold (2.6 vs 0.4 mm) and more
      than 2-fold greater (1.2 vs 0.5 mm) than in their node-negative peers. Node
      positive carriers revealed an annual rate of lymph node metastasis of 0.6-0.7
      nodes independent of ATA class. CONCLUSIONS: Small MTCs may take longer than 10
      years to become big enough to visualize on imaging. These slow growth rates
      highlight the importance of following up on patients for very long time periods
      to uncover at least some tumoral sources of persistent calcitonin production.

PMID- 24297799
TI  - Functional activities of mutant calcium-sensing receptors determine clinical
      presentations in patients with autosomal dominant hypocalcemia.
AB  - OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a congenital isolated
      hypoparathyroidism caused by activating mutations in the calcium-sensing receptor
      (CASR) gene. The clinical features of ADH are heterogeneous; some patients are
      asymptomatic, and others show severe hypocalcemia with Bartter's syndrome. We
      therefore recruited 12 patients with ADH to clarify the determinants of their
      clinical presentation. DESIGN AND METHODS: We studied two sporadic and 10
      familial cases of ADH. Serum concentrations of calcium, intact PTH, and magnesium
      (Mg(2+)) were measured in each patient. Fractional excretion of Mg (FE(Mg)) was
      calculated in spot urine samples. A nuclear factor of activated T cells
      luciferase assay was used to analyze the responsiveness of each mutant CaSR to
      extracellular Ca(2+). RESULTS: Genomic analysis revealed five known activating
      mutations and a novel mutation, E481K, in the CASR. Patients with the A843E,
      C131W, or F788C mutation showed hypomagnesemia with elevated FE(Mg). Intact PTH
      in these patients was consistently near the detection limit. In contrast,
      patients with the P221L, K47N, or E481K mutation exhibited normal Mg(2+) levels.
      In these patients, intact PTH increased in response to low calcium, and their
      maximum intact PTH exceeded the lower limit of the reference range. Functional
      analysis showed an association between the disease severity and the in vitro
      activity of the mutant CaSR. CONCLUSIONS: The functional activity of mutant CaSR
      determines the serum Mg(2+) level, renal Mg(2+) handling, and intact PTH in
      patients with ADH. The presence of hypomagnesemia with elevated FE(Mg) may
      indicate the diagnosis of ADH among patients with PTH-deficient
      hypoparathyroidism.

PMID- 24297800
TI  - Medial medullary infarction with central sparing.
AB  - A 35-year-old woman had cardiac arrest requiring treatment with a left
      ventricular assist device. After regaining consciousness, examination revealed
      upbeating nystagmus, otherwise normal bulbar function, left arm dysmetria, and
      numbness periorally and in areas she described as "a turtleneck of numbness with
      a T-shirt of sensation" (figure 1). 

PMID- 24297801
TI  - Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk.

PMID- 24297802
TI  - Treatment with statins and ischemic stroke severity: does the dose matter?

PMID- 24297803
TI  - Provocation of migraine with aura using natural trigger factors.

PMID- 24297804
TI  - Journal Club. Default-mode network connectivity in cognitively unimpaired
      patients with Parkinson disease.
AB  - This Journal Club article looks at a study by Tessitore et al.,(1) who
      investigated functional connectivity (FC) within the default-mode network (DMN)
      in cognitively unimpaired patients with Parkinson disease (PD). PD is the second
      most common neurodegenerative disorder after Alzheimer disease (AD) and is
      expected to become progressively more prevalent in our aging societies. Thus, its
      social and economic burden on societies is expected to be even greater in the
      future.(2) Cognitive impairment is one of the most disabling nonmotor symptoms of
      PD, further affecting functioning and quality of life, as well as increasing
      caregivers' burden and health-related costs.(3) When an individual is alert but
      not actively engaged in cognitive tasks, organized neural activity occurs in a
      set of brain regions called DMN (figure), which involves the posterior cingulate
      cortex (PCC), parts of the ventromedial prefrontal cortex, and the precuneus.(4)
      Interestingly, DMN abnormalities have been linked to cognitive profiles in
      several neurologic and psychiatric disorders, such as AD, autism, frontotemporal
      dementia, multiple sclerosis, and vegetative states(5); however, contradictory
      results have been reported in PD.(1) This study, for the first time, cogently
      demonstrates decreased FC within the DMN in cognitively unimpaired patients with
      PD. 

PMID- 24297805
TI  - Teaching neuroimages: isolated sphenoiditis: an uncommon cause of abducens nerve
      palsy.
AB  - A 35-year-old woman presented with a headache lasting 2 weeks and complained of
      recent diplopia. Neurologic examination showed limited left eye abduction.
      Initial brain CT scan was considered normal (figure, A). Brain MRI showed left
      sphenoiditis (figure, B). The patient was treated with amoxicillin/clavulanic
      acid and corticosteroids with rapid symptom improvement which deferred endoscopy
      that could provide a bacteriologic diagnosis. 

PMID- 24297806
TI  - Teaching neuroimages: thalamic aphasia syndrome.

PMID- 24297807
TI  - Classifying a smoker scale in adult daily and nondaily smokers.
AB  - INTRODUCTION: Smoker identity, or the strength of beliefs about oneself as a
      smoker, is a robust marker of smoking behavior. However, many nondaily smokers do
      not identify as smokers, underestimating their risk for tobacco-related disease
      and resulting in missed intervention opportunities. Assessing underlying beliefs
      about characteristics used to classify smokers may help explain the discrepancy
      between smoking behavior and smoker identity. This study examines the factor
      structure, reliability, and validity of the Classifying a Smoker scale among a
      racially diverse sample of adult smokers. METHODS: A cross-sectional survey was
      administered through an online panel survey service to 2,376 current smokers who
      were at least 25 years of age. The sample was stratified to obtain equal numbers
      of 3 racial/ethnic groups (African American, Latino, and White) across smoking
      level (nondaily and daily smoking). RESULTS: The Classifying a Smoker scale
      displayed a single factor structure and excellent internal consistency (alpha =
      .91). Classifying a Smoker scores significantly increased at each level of
      smoking, F(3,2375) = 23.68, p < .0001. Those with higher scores had a stronger
      smoker identity, stronger dependence on cigarettes, greater health risk
      perceptions, more smoking friends, and were more likely to carry cigarettes.
      Classifying a Smoker scores explained unique variance in smoking variables above
      and beyond that explained by smoker identity. CONCLUSIONS: The present study
      supports the use of the Classifying a Smoker scale among diverse, experienced
      smokers. Stronger endorsement of characteristics used to classify a smoker (i.e.,
      stricter criteria) was positively associated with heavier smoking and related
      characteristics. Prospective studies are needed to inform prevention and
      treatment efforts.

PMID- 24297808
TI  - Cotinine and tobacco-specific carcinogen exposure among nondaily smokers in a
      multiethnic sample.
AB  - BACKGROUND: Nondaily smoking has increased among current U.S. smokers during the
      past decade and is practiced by a significant percentage of smokers. Although
      research in nondaily smoking has grown, little is known about levels of exposure
      to tobacco toxicants among nondaily smokers and their variation across ethnic
      groups. METHODS: We examined urinary levels of cotinine and a tobacco-specific
      nitrosamine (NNAL) in community participants. Associations between the biomarker
      data and smoking characteristics were evaluated with Spearman's correlation
      analysis. RESULTS: Participants included 28 Blacks, 4 Latinos, and 25 Whites who
      smoked at least 1 cigarette on 4-24 days in the past 30 days. Participants
      averaged 3.3 (SD = 2.1) cigarettes per day (cpd) on days smoked, they smoked an
      average of 13.0 (SD = 5.4) days in the past month, and they smoked nondaily for
      10.5 (SD = 10.5) years. Median levels of creatinine-normalized cotinine and NNAL
      were 490.9 ng/mg and 140.7 pg/mg, respectively. NNAL and cotinine were highly
      correlated (r = .84); NNAL and cotinine were modestly correlated with cpd (r =
      .39 and r = .34; all p values <.05). The number of days smoked per month was not
      associated with any biomarker levels. CONCLUSIONS: Our findings demonstrate that
      nondaily smokers are, on average, exposed to significant levels of nicotine and
      carcinogenic nitrosamines, with exposures of 40%-50% of those seen in daily
      smokers. This level of exposure suggests a significant health risk. Nicotine and
      carcinogen exposure is most closely related to number of cigarettes smoked per
      day but not to number of days per month of smoking.

PMID- 24297809
TI  - Comparison of 18F-fluoride PET/CT, 18F-FDG PET/CT and bone scintigraphy (planar
      and SPECT) in detection of bone metastases of differentiated thyroid cancer: a
      pilot study.
AB  - OBJECTIVE: We compared the efficacies of 18F-fluoride positron emission
      tomography (18F-fluoride PET)/CT, 18F-fludeoxyglucose PET (18F-FDG PET)/CT, and
      99mTc bone scintigraphy [planar and single photon emission CT (SPECT)] for the
      detection of bone metastases in patients with differentiated thyroid carcinoma
      (DTC). METHODS: We examined 11 patients (8 females and 3 males; mean age 6
      standard deviation, 61.968.7 years) with DTC who had been suspected of having
      bone metastases after total thyroidectomy and were hospitalized to be given 131I
      therapy. Bone metastases were verified either when positive findings were
      obtained on both 131I scintigraphy and CT or when MRI findings were positive if
      MRI was performed. RESULTS: Metastases were confirmed in 24 (13.6%) of 176 bone
      segments in 9 (81.8%) of the 11 patients. The sensitivities of 18F-fluoride
      PET/CT and 99mTc bone scintigraphy (SPECT) were significantly higher than those
      of 18F-FDG PET/CT and 99mTc bone scintigraphy (planar) (p,0.05). The accuracies
      of 18F-fluoride PET/CT and mTc bone scintigraphy (SPECT) were significantly
      higher than that of 99mTc bone scintigraphy (planar) (p,0.05). CONCLUSION: The
      sensitivity and accuracy of 18F-fluoride PET/CT for the detection of bone
      metastases of DTC are significantly higher than those of 99mTc bone scintigraphy
      (planar). However, the sensitivity and accuracy of 99mTc bone scintigraphy
      (planar) are improved near to those of 18F-fluoride PET/CT when SPECT is added to
      a planar scan. The sensitivity of 18F-FDG PET/CT is significantly lower than that
      of 18F-fluoride PET/CT or 99mTc bone scintigraphy (SPECT).

PMID- 24297810
TI  - The assessment of round lytic lesions in sternotomies.
AB  - OBJECTIVE: The aims of this study were to define imaging findings and to identify
      any predisposing factors for the development of the round lytic lesion across the
      margins of sternotomy during the process of bone healing. METHODS: We searched
      all chest CT scans performed between 2007 and 2012 and selected patients who had
      three studies performed in the recent, late and latest post-operative periods.
      Patients presenting any complications related to wound healing were excluded from
      the study. CT features of the sternotomy and possible instability factors were
      assessed. RESULTS: From 15689 chest CT images analysed, 68 patients fulfilled the
      criteria. The development of a round lytic lesion was observed in 35 and 39
      patients in the late and latest post-operative periods, respectively, and there
      was an association between mild misalignment of margins in the recent post
      operative period and the development of a round lesion in the follow-up periods
      (p=0.010 and p=0.002, respectively). CONCLUSION: Sternotomies exhibit a delayed
      and unusual pattern of bone healing, and minimal instability factors during bone
      closure could trigger the development of a lytic lesion that is part of the
      normal healing process. ADVANCES IN KNOWLEDGE: This lytic bone lesion is part of
      the bone healing, and its appearance should not be mistaken as infection or
      malignancy, even in a suggestive clinical setting.

PMID- 24297811
TI  - In vitro screening of compounds against laboratory and field isolates of human
      hookworm reveals quantitative differences in anthelmintic susceptibility.
AB  - A panel of 80 compounds was screened for anthelmintic activity against a
      laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm
      obtained from school children in the Kintampo North District of the Brong Ahafo
      Region of Ghana. Although the laboratory strain of A. ceylanicum was more
      susceptible to the compounds tested than the field isolates of hookworm, a
      twofold increase in compound concentration resulted in comparable egg hatch
      percent inhibition for select compounds. These data provide evidence that the
      efficacy of anthelmintic compounds may be species-dependent and that field and
      laboratory strains of hookworm differ in their sensitivities to the anthelmintics
      tested. These data also suggest that both compound concentration and hookworm
      species must be considered when screening to identify novel anthelmintic
      compounds.

PMID- 24297812
TI  - Ocular onchocerciasis in the Yanomami communities from Brazilian Amazon: effects
      on intraocular pressure.
AB  - To determine the influence of onchocercal eye disease on the intraocular pressure
      of the Yanomami Tribe Aratha-u of Roraima State, Brazil, considered endemic for
      onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam
      that included external examination, slit lamp examination, intraocular pressure
      measurement, and a fundus ophthalmoscope examination. A high prevalence of
      onchocerciasis-related eye lesions was encountered in 68.6% of the patients.
      Punctate keratitis and microfilariae in the anterior chamber were found in ~28%.
      The mean of intraocular eye pressure found was 10.47 mm of Hg.

PMID- 24297813
TI  - Changes in knowledge of bat rabies and human exposure among United States cavers.
AB  - The purpose of the study was to evaluate changes in the knowledge of bat rabies
      and human exposure among United States cavers during the last decade. A survey
      was distributed among cavers who attended the National Speleological Society
      convention in 2000 and those who attended in 2010. In 2000 and 2010, 392 and 108
      cavers, respectively, responded to the questionnaire. Eighty-five per cent of
      respondents in 2000 indicated a bat bite as a risk for rabies compared with all
      respondents in 2010 (P < 0.0001 controlling for age). The proportion of
      respondents indicating that they were advised to receive rabies pre-exposure
      prophylaxis (PreEP) because of caving increased (17% and 29%; P = 0.03
      controlling for age). Among these, PreEP was received by 56% and 45%. Although
      recognition of the risk of rabies exposure from bats is important, the proportion
      of cavers acting on current recommendations regarding PreEP does not appear to
      have improved in the past decade.

PMID- 24297814
TI  - Characterization based on the 56-Kda type-specific antigen gene of Orientia
      tsutsugamushi genotypes isolated from Leptotrombidium mites and the rodent host
      post-infection.
AB  - Abstract. Characterization of the 56-kDa type-specific antigen (TSA) genes of
      Orientia tsutsugamushi (OT) from three naturally infected, laboratory-reared mite
      colonies comprising three species (Leptotrombidium deliense [Ld], Leptotrombidium
      imphalum [Li], and Leptotrombidium chiangraiensis [Lc]) has revealed the presence
      of single and coexisting OT genotypes found in individual chiggers. The Karp
      genotype was found in all of the chiggers examined, whereas Gilliam and UT302
      genotypes were only observed in combination with the Karp genotype. From analysis
      of these OT genotypes after transmission from chiggers to mice it was determined
      that with the Lc and Li mites, the OT genotype composition in the rodent spleens
      post-infection had not changed and therefore resembled that observed in the
      feeding chiggers. However, only the Karp genotype was found in rodents after
      feeding by Ld chiggers carrying Karp and Gilliam genotypes. The current findings
      reveal a complex association among the host, pathogen, and vector. 

PMID- 24297815
TI  - Training programs within global networks: lessons learned in the Fogarty
      International Clinical Research Scholars and Fellows Program.
AB  - The Fogarty International Clinical Research Scholars and Fellows Support Center
      at Vanderbilt describes administrative lessons learned from the management of 436
      scholars (American students or host country junior trainees) and 122 post
      doctoral fellows (Americans or host country nationals). Trainees spent 10-11
      months working on mentored research projects at 61 well-vetted sites in 27 low-
      or middle-income host countries (LMICs) with strong US partners. Economies of
      scale, strong centralized information exchange, and effective standardized
      operations linking US institutions with LMIC field sites were achieved in a
      program that minimized administrative overhead. Advantages and drawbacks of this
      approach are presented and discussed. Training of a new generation of global
      research leaders is greatly facilitated by an overseas mentored research
      experience that is administratively streamlined to optimize the use of resources
      for training, research, and capacity building.

PMID- 24297817
TI  - Role of vitamin D in atherosclerosis.

PMID- 24297816
TI  - Immunoblotting with human native antigen shows stage-related sensitivity in the
      serodiagnosis of hepatic cystic echinococcosis.
AB  - The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and
      confirmed by serology. However, no biological marker of cyst viability is
      currently available implying years-long patient follow-up, which is not always
      feasible in endemic areas. We characterized the performance of an immunoblotting
      test based on human hydatid cyst fluid with particular regard to its ability to
      distinguish between cyst stages. Sera from patients with cysts in different
      stages showed distinctive band pattern recognition. Most importantly, the test
      discriminated in 80% of cases CE3a from CE3b transitional cysts, known to have
      different viability profiles. Interestingly, we observed a rapid change in band
      pattern recognition of sera from one patient at time points when his cyst passed
      from active to transitional to inactive stages. Further identification of
      different antigens expressed by different cyst stages will support the
      development of diagnostic tools that could early define cyst viability, to guide
      clinical decision making, and shorten patient follow-up.

PMID- 24297818
TI  - Pulseless electric activity: definition, causes, mechanisms, management, and
      research priorities for the next decade: report from a National Heart, Lung, and
      Blood Institute workshop.

PMID- 24297819
TI  - Congenital rubella syndrome presenting in adulthood with fatigue.

PMID- 24297820
TI  - Fulminant human herpesvirus 6 myocarditis in an immunocompetent adult: role of
      cardiac magnetic resonance in a multidisciplinary approach.

PMID- 24297821
TI  - Letter by De Mattia et al regarding article, "Digital clubbing".

PMID- 24297822
TI  - Response to letter regarding article, "Digital clubbing".

PMID- 24297824
TI  - The effect of leaving employment on mental health: testing 'adaptation' versus
      'sensitisation' in a cohort of working-age Australians.
AB  - OBJECTIVES: To investigate the 'adaptation' versus 'sensitisation' hypotheses in
      relation to mental health and labour market transitions out of employment to
      determine whether mental health stabilised (adaptation) or worsened
      (sensitisation) as people experienced one or more periods without work. METHODS:
      The Household Income and Labour Dynamics of Australia (HILDA) longitudinal survey
      was used to investigate the relationship between the number of times a person had
      been unemployed or had periods out of the labour force (ie, spells without work)
      and the Mental Component Summary (MCS) of the Short Form 36 (SF-36). Demographic,
      health and employment related confounders were included in a series of multilevel
      regression models. RESULTS: During 2001-2010, 3362 people shifted into
      unemployment and 1105 shifted from employment to not in the labour force.
      Compared with participants who did not shift, there was a 1.64-point decline (95%
      CI -2.05 to -1.23, p<0.001) in scores of the MCS SF-36 among those who had one
      spell of unemployment (excluding not in the labour force), and a 2.56-point
      decline (95% CI -3.93 to -1.19, p<0.001) among those who had two or more spells
      of unemployment after adjusting for other variables. Findings for shifts from
      employment to 'not in the labour force' were in the same direction; however,
      effect sizes were smaller. CONCLUSIONS: These results indicate that multiple
      spells of unemployment are associated with continued, though small, declines in
      mental health. Those who leave employment for reasons other than unemployment
      experience a smaller reduction in mental health.

PMID- 24297826
TI  - Standing-based office work shows encouraging signs of attenuating post-prandial
      glycaemic excursion.
AB  - OBJECTIVES: The main aim of this study was to compare two days of continuous
      monitored capillary blood glucose (CGM) responses to sitting and standing in
      normally desk-based workers. DESIGN, SETTING AND PARTICIPANTS: This open repeated
      measures study took place in a real office environment, during normal working
      hours and subsequent CGM overnight measures in 10 participants aged 21-61 years
      (8 female). MAIN OUTCOMES: Postprandial (lunch) measures of: CGM, accelerometer
      movement counts (MC) heart rate, energy expenditure (EE) and overnight CGM
      following one afternoon of normal sitting work compared with one afternoon of the
      same work performed at a standing desk. RESULTS: Area-under-the-curve analysis
      revealed an attenuated blood glucose excursion by 43% (p=0.022) following 185 min
      of standing (143, 95% CI 5.09 to 281.46 mmol/L min) compared to sitting work
      (326; 95% CI 228 to 425 mmol/L min). Compared to sitting, EE during an afternoon
      of standing work was 174 kcals greater (0.83 kcals/min; p=0.028). The
      accelerometer MC showed no differences between the afternoons of seated versus
      standing work; reported differences were thus a function of the standing work and
      not from additional physical movements around the office. CONCLUSIONS: This is
      the first known 'office-based' study to provide CGM measures that add some of the
      needed mechanistic information to the existing evidence-base on why avoiding
      sedentary behaviour at work could lead to a reduced risk of cardiometabolic
      diseases.

PMID- 24297825
TI  - Gender differences in the effect of occupational endotoxin exposure on impaired
      lung function and death: the Shanghai Textile Worker Study.
AB  - OBJECTIVE: Airborne endotoxin exposure has adverse and protective health effects.
      Studies show men have augmented acute inflammatory responses to endotoxin. In
      this longitudinal cohort study we investigated the effect of long-term exposure
      to endotoxin in cotton dust on health, and determined whether these effects
      differ by gender. METHODS: In the Shanghai Textile Worker Study, 447 cotton and
      472 control silk textile workers were followed from 1981 to 2011 with repeated
      measures of occupational endotoxin exposure, spirometry and health
      questionnaires. Impaired lung function was defined as a decline in forced
      expiratory volume in one second to less than the 5th centile of population
      predicted. Death was ascertained by death registries. We used Cox proportional
      hazards models to assess the effect of endotoxin exposure on the time to
      development of impaired lung function and death. RESULTS: 128 deaths and 164
      diagnoses of impaired lung function were ascertained between 1981 and 2011. HRs
      for the composite end point of impaired lung function or death was 1.47 (95% CI
      1.09 to 1.97) for cotton vs silk workers and 1.04 (95% CI 1.01 to 1.07) per 10
      000 endotoxin units (EU)/m(3)-years increase in exposure. HRs for all-cause
      mortality was 1.36 (95% CI 0.93 to 1.99) for cotton vs silk workers and 1.04 (95%
      CI 0.99 to 1.08) per 10 000 EU/m(3)-years. The risk associated with occupational
      endotoxin exposure was elevated only in men. CONCLUSIONS: Occupational endotoxin
      exposure is associated with an increase in the risk of impaired lung function and
      all-cause mortality in men.

PMID- 24297827
TI  - [Scientific reports: responsibility for quality].

PMID- 24297828
TI  - [An analysis of the individual perception and coping strategies of people with
      dementia in the early stage of their disease in accordance to the function and
      effectiveness of self-help groups on the basis of self-expression].
AB  - Society paints an inconsistent picture of people with dementia: on the one hand
      they are people who can basically think and act (even) self-determinate. But on
      the other hand they need support and help from outside in daily routine. Self
      help groups are a possible form of support. There are actually no research
      results to decide if this form of intervention is appropriate to people with
      dementia or not. The question must be answered in which way people in the early
      stage of dementia perceive their illness and what kind of influence the
      intervention of a support group has on their self-concept. In the first survey
      period five focus groups and eight narrative biographically oriented interviews
      are performed. The following results are noted: People with dementia are exposed
      to processes of incapacitation. It is well intentioned (in order to help them),
      but in reality they are forced to do something they probably don't like. They
      must bear unwanted interventions. In contrast, the self-help groups promote
      recognition processes. Finding internal security and being able to accept the
      illness are some of the most important functions. Independent living with
      dementia is supported. Two conclusions can be drawn: Forms of incapacitation from
      outside must be reduced. Self-help groups in a support role should accordingly
      supply the existing care services for people with dementia. The support of self
      help groups should be the provision/improvement of the existing care services for
      people with dementia. 

PMID- 24297829
TI  - [German translation of Suicidal Patient Observation Chart (SPOC) - an instrument
      for practice].
AB  - Nursing of suicidal in-patients is a complex and responsible task. A direct and
      immediate intensive caring and therapeutic supervision, also known as special
      observation is still recommended in guidelines (DGPPN, 2012) and maybe one of the
      most used interventions in the caring of suicidal patients in inpatient settings.
      It involves many kinds to develop the relationship between the observer and the
      patient. The original SPOC was developed in Sweden with the aim to increase the
      quality of a systematically documentation during the supervision of suicidal
      patients. It is an instrument to ensure systematic documentation of observational
      behavior or noticeable mood during acute suicidal crisis, for example feelings
      like "worried, anxious" or other possible influencing factors like "sudden mood
      variation". By this means the SPOC can ensure the process of systematic
      documentation of special observation and increase its quality, i. e. who
      documented what at what time. Furthermore SPOC can facilitate a better
      communication of the observation process to the multidisciplinary team and to the
      patient as well. The SPOC includes the 28 items and covers 24 separate
      observation periods. The aim of this paper is to constitute the translation
      process from the English to the German SPOC version. The translation process
      followed a five step model. In the first step the English version was translated
      from two German native speakers. In the second step, the first two translation
      results where discussed by the Expert group (authors) and a new version was
      developed. In the third step the first german version was translated back (two
      English native Speakers) into English. The fourth step was taken, to review the
      results by the expert groups (authors) and set up the so called "pre version".
      The last step includes the proof of content validity by 52 nurses. The proof was
      able to identify a few misunderstandings and helped to enhance the tool in its
      final version. With the translation, the German-speaking nursing practice in
      psychiatry has a tool that can be used by psychiatric nurses regarding their
      complex interventions to be undertaken in this special group of patients.

PMID- 24297830
TI  - [Voluntary Refusal of Food and Fluid in palliative care: a mapping literature
      review].
AB  - Voluntary Refusal of Food and Fluid (VRFF) is one possibility for patients in
      palliative situations to hasten death and avoid further suffering. By means of a
      mapping literature review this article describes the medical, nursing, ethical
      and legal perspective of care for people who wish to hasten death using VRFF. The
      results show that the wish to die is affected by psychological, social, spiritual
      and physical factors. VRFF is a little-known, legal and independently viable
      method to hasten death. Reducing fluid intake to 40 ml daily, the dying process
      takes one to three weeks. VRFF can be regarded as a natural death, foregoing
      treatment or as suicide. In contrast to physician assisted suicide or euthanasia,
      patients dying by VRFF experience a "natural" dying process and the decision is
      reversible in the first few days. As authority to act lies with the person
      wishing to die professionals and family caring for the dying are practicing
      palliative care, as opposed to assisted suicide or euthanasia. Professionals and
      family involved in the decision-making process are confronted with various
      ethical problems. Further research concerning VRFF and its implications for
      practice is necessary. 

PMID- 24297831
TI  - [Evaluation of pediatric Advanced Practice Nurse: quality and benefit for
      Switzerland?].

PMID- 24297832
TI  - [Theory development in grounded theory].

PMID- 24297835
TI  - Genetics and genomics for the prevention and treatment of cardiovascular disease:
      update: a scientific statement from the American Heart Association.

PMID- 24297836
TI  - Is previous history a reliable predictor for acute mountain sickness
      susceptibility? A meta-analysis of diagnostic accuracy.
AB  - PURPOSE: The goal of this meta-analysis was to determine the clinical utility of
      acute mountain sickness (AMS) history to predict future incidents of AMS. METHOD:
      17 studies (n=7921 participants) were included following a systematic review of
      the literature. A bivariate random-effects model was used to calculate the
      summary sensitivity and specificity of the diagnostic test, and moderator
      variables were tested to explain the heterogeneity across studies. The Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was used to assess
      concerns for bias and applicability for the included studies. RESULTS: The
      history of AMS had a low diagnostic accuracy for the prediction of future AMS
      incidents: the summary sensitivity was 0.50 (95% CI (0.40 to 0.59)) and the
      summary specificity was 0.72 (95% CI (0.66 to 0.78)). There was significant
      heterogeneity in the sensitivity and specificity across studies, which we
      modelled using moderator analysis. Studies that restricted the use of
      acetazolamide and dexamethasone had not only a higher sensitivity (0.66) relative
      to those that did not (0.44; p=0.03) but also an increased false-positive rate
      (0.39 vs 0.23, p=0.03). The QUADAS-2 analysis showed that AMS histories were
      insufficiently detailed, and few studies controlled for prophylactic medication
      use or recent altitude exposure, leading to high risks of bias and concerns for
      applicability. CONCLUSIONS: The use of AMS history to guide prophylactic
      strategies for high-altitude ascent is not supported by the literature; however,
      the low sensitivity and specificity of this diagnostic test could reflect the
      quality of the available studies. Ensuring that the characteristics of the
      history and future ascents are similar may improve the clinical utility of AMS
      history.

PMID- 24297838
TI  - [World veterinary association - for one profession, one vision, one voice].

PMID- 24297837
TI  - Using accelerometers to measure physical activity in large-scale epidemiological
      studies: issues and challenges.
AB  - BACKGROUND: The current guidelines for aerobic activity require that adults carry
      out >=150 min/week of moderate-intensity physical activity, with a large body of
      epidemiological evidence showing this level of activity to decrease the incidence
      of many chronic diseases. Less is known about whether light-intensity activities
      also have such benefits, and whether sedentary behaviour is an independent
      predictor of increased risks of these chronic diseases, as imprecise assessments
      of these behaviours and cross-sectional study designs have limited knowledge to
      date. METHODS: Recent technological advances in assessment methods have made the
      use of movement sensors, such as the accelerometer, feasible for use in
      longitudinal, large-scale epidemiological studies. Several such studies are
      collecting sensor-assessed, objective measures of physical activity with the aim
      of relating these to the development of clinical endpoints. This is a relatively
      new area of research; thus, in this article, we use the Women's Health Study
      (WHS) as a case study to illustrate the challenges related to data collection,
      data processing and analyses of the vast amount of data collected. RESULTS: The
      WHS plans to collect 7 days of accelerometer-assessed physical activity and
      sedentary behaviour in ~18 000 women aged >=62 years. Several logistical
      challenges exist in collecting data; nonetheless, as of 31 August 2013, 11 590
      women have already provided some data. In addition, the WHS experience on data
      reduction and data analyses can help inform other similar large-scale
      epidemiological studies. CONCLUSIONS: Important data on the health effects of
      light-intensity activity and sedentary behaviour will emerge from large-scale
      epidemiological studies collecting objective assessments of these behaviours.

PMID- 24297839
TI  - [Experiences with pain control during piglet castration in Switzerland Part 1:
      Inhalation anesthesia].
AB  - The objectives of this study were a description of the practical implementation
      of the painless castration under inhalational anaesthesia with an objective
      assessment of animal welfare, workplace safety and time exposure. 600
      questionnaires were sent to farmers all over Switzerland and 100 farms were
      visited during castration under inhalation anaesthesia. 44 % of the visited
      farmers administered analgetics during anaesthesia or less than 10 minutes before
      castration. 14 % of the piglets were insufficiently anaesthetised (moving or
      vocalising) and 18 % showed stronger bleeding tendency after castration. The
      mortality rate was less than 0.1 %. 22 % of the swine farmers reported headache
      or dizziness during or after castration work. The Isoflurane level on 2 farms was
      above the Swiss safety limits. The time needed for castration was with 4.3
      minutes clearly above the time necessary without anaesthesia. The additional
      financial costs and time are at the moment not adequately compensated to the
      farmers. 

PMID- 24297840
TI  - [Experiences with pain control during piglet castration in Switzerland Part 2:
      Injection anesthesia].
AB  - The aim of this study was to describe the practical implementation of the
      painless castration under injection anaesthesia in Switzerland. 30 swine farms
      were visited and 60 farmers answered a questionnaire. 34 % of the piglets showed
      movements during castration under injection anaesthesia and 17 % had excitations
      during recovery from anaesthesia. After 48 minutes half of the piglets were in
      sternal position and after 112 minutes half of them showed coordinated movements.
      The body temperature decreased by 3.1  degrees C until 60 minutes after
      castration, especially small piglets reached critical temperature levels. 38 % of
      the piglets showed strong bleeding after castration. The healing of the wound was
      good according to 82 % of the farmers. 83 % of the farmers reported piglet
      losses, especially at the beginning of the anaesthesia period. The anaesthesia
      may be improved by using butorphanol in addition to the combination of ketamine
      and azaperone. The recovery of the piglets should be in a warm place without any
      risk of injury by obstacles or the sow. Increased bleeding can be controlled by
      using an emasculator. 

PMID- 24297841
TI  - Racemic ketamine in comparison to S-ketamine in combination with azaperone and
      butorphanol for castration of pigs.
AB  - In this prospective blinded randomised study, 28 male 9 week old pigs of
      bodyweight 25 kg, were anaesthetised for castration using 5 mg/kg azaperone, 0.2
      mg/kg butorphanol and 0.4 mg/kg meloxicam, in conjunction with either 15 mg/kg
      racemic ketamine (Keta-Race) or 9 mg/kg S-ketamine (S-Keta), all drugs being
      injected intramuscularly. Anaesthesia induction, maintenance and recovery were
      timed and scored. Insufficient anaesthesia was supplemented with 1/4 the initial
      dose of ketamine or S-ketamine, respectively, administered intravenously. A t
      test was utilised for analysis of timings, and, for repeated recovery time data,
      ANOVA was used. In relation to quantification and timing of supplemental drug
      doses, a chi square test was used and the scoring was analysed by two sample
      Wilcoxon rank-sum test. Ketamine re-dosing was required in 23 animals on a total
      of 46 occasions distributed evenly throughout both groups. The only group
      differences occurred during recovery, with the S-Keta group showing earlier
      movements, sternal recumbency and ability to stand. Three pigs in each group
      showed muscle fasciculations during the recovery period, while an additional two
      animals of the Keta-Race group exhibited marked and unacceptable paddling in
      recovery. In conclusion, S-ketamine at a dose rate of 60 % of that of racemic
      ketamine induced comparable anaesthesia for castration in pigs, but with superior
      recovery characteristics. 

PMID- 24297842
TI  - Suppression of boar taint in cryptorchid pigs using a vaccine against the
      gonadotropin-releasing hormone.
AB  - Thirteen unilaterally cryptorchid Large White pigs, which had been immunized at 4
      and 8 weeks of age and a third time at 64 +/- 4 kg body weight against the
      gonadotropin releasing hormone with the vaccine Improvac(r), were slaughtered at
      the age of 170 +/- 9 days at a body weight of 102 +/- 12 kg. Twelve pigs tested
      negative in the olfactory test of the salivary gland; their descended testicles
      were small and their fat androstenone concentration was low compared to normally
      developed boars of a previous experiment which had been vaccinated twice with
      Improvac(r) according the manufacturer's recommendation. One cryptorchid boar,
      which tested positive in the olfactory test and whose testicular weight and fat
      androstenone concentration corresponded to values of unvaccinated boars of the
      same age, obviously had not responded to the vaccination. It is an open question
      if the vaccination protocol for normal boars is sufficient to prevent boar taint
      in the majority of cryptorchid pigs, too. 

PMID- 24297843
TI  - [Epidemiologic study of an outbreak of progressive rhinitis atrophicans in a
      breeding sow facility in Lucerne canton].

PMID- 24297846
TI  - Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling
      and function.
AB  - Lacrimal glands function to produce an aqueous layer, or tear film, that helps to
      nourish and protect the ocular surface. Lacrimal glands secrete proteins,
      electrolytes and water, and loss of gland function can result in tear film
      disorders such as dry eye syndrome, a widely encountered and debilitating disease
      in ageing populations. To combat these disorders, understanding the underlying
      molecular signalling processes that control lacrimal gland function will give
      insight into corrective therapeutic approaches. Previously, in single lacrimal
      cells isolated from lacrimal glands, we demonstrated that muscarinic receptor
      activation stimulates a phospholipase C-coupled signalling cascade involving the
      inositol trisphosphate-dependent mobilization of intracellular calcium and the
      subsequent activation of store-operated calcium entry (SOCE). Since intracellular
      calcium stores are finite and readily exhausted, the SOCE pathway is a critical
      process for sustaining and maintaining receptor-activated signalling. Recent
      studies have identified the Orai family proteins as critical components of the
      SOCE channel activity in a wide variety of cell types. In this study we
      characterize the role of Orai1 in the function of lacrimal glands using a mouse
      model in which the gene for the calcium entry channel protein, Orai1, has been
      deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not
      exhibit SOCE following activation of the muscarinic receptor. In comparison with
      wild-type and heterozygous littermates, Orai1 knockout mice showed a significant
      reduction in the stimulated tear production following injection of pilocarpine, a
      muscarinic receptor agonist. In addition, calcium-dependent, but not calcium
      independent exocytotic secretion of peroxidase was eliminated in glands from
      knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in
      lacrimal gland signalling and function. 

PMID- 24297847
TI  - Age-related changes in afferent pathways and urothelial function in the male
      mouse bladder.
AB  - The prevalence of lower urinary tract storage disorders such as overactive
      bladder syndrome and urinary incontinence significantly increase with age.
      Previous studies have demonstrated age-related changes in detrusor function and
      urothelial transmitter release but few studies have investigated how the
      urothelium and sensory pathways are affected. The aim of this study was to
      investigate the effect of ageing on urothelial-afferent signalling in the mouse
      bladder. Three-month-old control and 24-month-old aged male mice were used. In
      vivo natural voiding behaviour, sensory nerve activity, urothelial cell function,
      muscle contractility, transmitter release and gene and protein expression were
      measured to identify how all three components of the bladder (neural, contractile
      and urothelial) are affected by ageing. In aged mice, increased voiding frequency
      and enhanced low threshold afferent nerve activity was observed, suggesting that
      ageing induces overactivity and hypersensitivity of the bladder. These changes
      were concurrent with altered ATP and acetylcholine bioavailability, measured as
      transmitter overflow into the lumen, increased purinergic receptor sensitivity
      and raised P2X3 receptor expression in the urothelium. Taken together, these data
      suggest that ageing results in aberrant urothelial function, increased afferent
      mechanosensitivity, increased smooth muscle contractility, and changes in gene
      and protein expression (including of P2X3). These data are consistent with the
      hypothesis that ageing evokes changes in purinergic signalling from the bladder,
      and further studies are now required to fully validate this idea. 

PMID- 24297848
TI  - Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin
      release in human skeletal muscle and adipose tissue: in vivo and in vitro
      studies.
AB  - Irisin was identified as a myokine secreted by contracting skeletal muscle,
      possibly mediating some exercise health benefits via 'browning' of white adipose
      tissue. However, a controversy exists concerning irisin origin, regulation and
      function in humans. Thus, we have explored Fndc5 gene and irisin protein in two
      clinical studies: (i) a cross-sectional study (effects of type 2 diabetes (T2D)
      in drug-naive men) and (ii) an intervention study (exercise effects in sedentary,
      overweight/obese individuals). Glucose tolerance and insulin sensitivity were
      assessed. Maximal aerobic capacity and muscle strength were measured before and
      after training. Body composition (magnetic resonance imaging), muscle and liver
      fat content (1H-magnetic resonance spectroscopy (MRS)) and in vivo muscle
      metabolism (32P-MRS) were determined. Skeletal muscle and subcutaneous abdominal
      adipose tissue samples were taken in the fasted state and during euglycaemic
      hyperinsulinaemia (adipose tissue) and before/after exercise training (muscle).
      We found that muscle Fndc5 mRNA was increased in prediabetes but not T2D. Fndc5
      in adipose tissue and irisin in plasma were reduced in T2D by 40% and 50%,
      respectively. In contrast, T2D-derived myotubes expressed/secreted the highest
      levels of Fndc5/irisin. Neither hyperinsulinaemia (adipose tissue/plasma) nor
      exercise (muscle/plasma) affected Fndc5/irisin in vivo. Circulating irisin was
      positively associated with muscle mass, strength and metabolism and negatively
      with fasting glycaemia. Glucose and palmitate decreased Fndc5 mRNA in myotubes in
      vitro. We conclude that distinct patterns of Fndc5/irisin in muscle, adipose
      tissue and circulation, and concordant in vivo down-regulation in T2D, indicate
      that irisin might distinguish metabolic health and disease. Moreover,
      Fndc5/irisin was discordantly regulated in diabetic muscle and myotubes in vitro,
      suggesting that whole body factors, such as glucose and fatty acids, might be
      important for irisin regulation. Exercise did not affect Fndc5/irisin. However,
      irisin was positively linked to muscle mass, strength and metabolism, pointing to
      common regulatory factors and/or the potential for irisin to modify muscle
      phenotype.

PMID- 24297849
TI  - Facilitation by intracellular carbonic anhydrase of Na+ -HCO3- co-transport but
      not Na+ / H+ exchange activity in the mammalian ventricular myocyte.
AB  - Carbonic anhydrase enzymes (CAs) catalyse the reversible hydration of CO2 to H+
      and HCO3- ions. This catalysis is proposed to be harnessed by acid/base
      transporters, to facilitate their transmembrane flux activity, either through
      direct protein-protein binding (a 'transport metabolon') or local functional
      interaction. Flux facilitation has previously been investigated by heterologous
      co-expression of relevant proteins in host cell lines/oocytes. Here, we examine
      the influence of intrinsic CA activity on membrane HCO3- or H+ transport via the
      native acid-extruding proteins, Na+ -HCO3- cotransport (NBC) and Na+ / H+
      exchange (NHE), expressed in enzymically isolated mammalian ventricular myocytes.
      Effects of intracellular and extracellular (exofacial) CA (CAi and CAe) are
      distinguished using membrane-permeant and -impermeant pharmacological CA
      inhibitors, while measuring transporter activity in the intact cell using pH and
      Na+ fluorophores. We find that NBC, but not NHE flux is enhanced by catalytic CA
      activity, with facilitation being confined to CAi activity alone. Results are
      quantitatively consistent with a model where CAi catalyses local H+ ion delivery
      to the NBC protein, assisting the subsequent (uncatalysed) protonation and
      removal of imported HCO3- ions. In well-superfused myocytes, exofacial CA
      activity is superfluous, most likely because extracellular CO2/HCO3- buffer is
      clamped at equilibrium. The CAi insensitivity of NHE flux suggests that, in the
      native cell, intrinsic mobile buffer-shuttles supply sufficient intracellular H+
      ions to this transporter, while intrinsic buffer access to NBC proteins is
      restricted. Our results demonstrate a selective CA facilitation of acid/base
      transporters in the ventricular myocyte, implying a specific role for the
      intracellular enzyme in HCO3- transport, and hence pHi regulation in the heart.

PMID- 24297850
TI  - Synaptic noise is an information bottleneck in the inner retina during dynamic
      visual stimulation.
AB  - In daylight, noise generated by cones determines the fidelity with which visual
      signals are initially encoded. Subsequent stages of visual processing require
      synapses from bipolar cells to ganglion cells, but whether these synapses
      generate a significant amount of noise was unknown. To characterize noise
      generated by these synapses, we recorded excitatory postsynaptic currents from
      mammalian retinal ganglion cells and subjected them to a computational noise
      analysis. The release of transmitter quanta at bipolar cell synapses contributed
      substantially to the noise variance found in the ganglion cell, causing a
      significant loss of fidelity from bipolar cell array to postsynaptic ganglion
      cell. Virtually all the remaining noise variance originated in the presynaptic
      circuit. Circuit noise had a frequency content similar to noise shared by
      ganglion cells but a very different frequency content from noise from bipolar
      cell synapses, indicating that these synapses constitute a source of independent
      noise not shared by ganglion cells. These findings contribute a picture of
      daylight retinal circuits where noise from cones and noise generated by synaptic
      transmission of cone signals significantly limit visual fidelity.

PMID- 24297851
TI  - Cholesterol and F-actin are required for clustering of recycling synaptic vesicle
      proteins in the presynaptic plasma membrane.
AB  - Synaptic vesicles (SVs) and their proteins must be recycled for sustained
      synaptic transmission. We tested the hypothesis that SV cholesterol is required
      for proper sorting of SV proteins during recycling in live presynaptic terminals.
      We used the reversible block of endocytosis in the Drosophila temperature
      sensitive dynamin mutant shibire-ts1 to trap exocytosed SV proteins, and then
      examined the effect of experimental treatments on the distribution of these
      proteins within the presynaptic plasma membrane by confocal microscopy. SV
      proteins synaptotagmin, vglut and csp were clustered following SV trapping in
      control experiments but dispersed in samples treated with the cholesterol
      chelator methyl-beta-cyclodextrin to extract SV cholesterol. There was
      accumulation of phosphatidylinositol (4,5)-bisphosphate (PIP2) in presynaptic
      terminals following SV trapping and this was reduced following SV cholesterol
      extraction. Reduced PIP2 accumulation was associated with disrupted accumulation
      of actin in presynaptic terminals. Similar to vesicular cholesterol extraction,
      disruption of actin by latrunculin A after SV proteins had been trapped on the
      plasma membrane resulted in the dispersal of SV proteins and prevented recovery
      of synaptic transmission due to impaired endocytosis following relief of the
      endocytic block. Our results demonstrate that vesicular cholesterol is required
      for aggregation of exocytosed SV proteins in the presynaptic plasma membrane and
      are consistent with a mechanism involving regulation of PIP2 accumulation and
      local actin polymerization by cholesterol. Thus, alteration of membrane or SV
      lipids may affect the ability of synapses to undergo sustained synaptic
      transmission by compromising the recycling of SV proteins.

PMID- 24297852
TI  - Effects of type 1 diabetes, sprint training and sex on skeletal muscle
      sarcoplasmic reticulum Ca2+ uptake and Ca2+-ATPase activity.
AB  - Calcium cycling is integral to muscle performance during the rapid muscle
      contraction and relaxation of high-intensity exercise. Ca(2+) handling is altered
      by diabetes mellitus, but has not previously been investigated in human skeletal
      muscle. We investigated effects of high-intensity exercise and sprint training on
      skeletal muscle Ca(2+) regulation among men and women with type 1 diabetes (T1D,
      n = 8, 3F, 5M) and matched non-diabetic controls (CON, n = 8, 3F, 5M).
      Secondarily, we examined sex differences in Ca(2+) regulation. Subjects undertook
      7 weeks of three times-weekly cycle sprint training. Before and after training,
      performance was measured, and blood and muscle were sampled at rest and after
      high-intensity exercise. In T1D, higher Ca(2+)-ATPase activity (+28%) and Ca(2+)
      uptake (+21%) than in CON were evident across both times and days (P < 0.05), but
      performance was similar. In T1D, resting Ca(2+)-ATPase activity correlated with
      work performed until exhaustion (r = 0.7, P < 0.01). Ca(2+)-ATPase activity, but
      not Ca(2+) uptake, was lower (-24%, P < 0.05) among the women across both times
      and days. Intense exercise did not alter Ca(2+)-ATPase activity in T1D or CON.
      However, sex differences were evident: Ca(2+)-ATPase was reduced with exercise
      among men but increased among women across both days (time * sex interaction, P <
      0.05). Sprint training reduced Ca(2+)-ATPase (-8%, P < 0.05), but not Ca(2+)
      uptake, in T1D and CON. In summary, skeletal muscle Ca(2+) resequestration
      capacity was increased in T1D, but performance was not greater than CON. Sprint
      training reduced Ca(2+)-ATPase in T1D and CON. Sex differences in Ca(2+)-ATPase
      activity were evident and may be linked with fibre type proportion differences.

PMID- 24297854
TI  - [The environment and medicine].

PMID- 24297853
TI  - The small GTPase Rac1 is required for smooth muscle contraction.
AB  - The role of the small GTP-binding protein Rac1 in smooth muscle contraction was
      examined using small molecule inhibitors (EHT1864, NSC23766) and a novel smooth
      muscle-specific, conditional, Rac1 knockout mouse strain. EHT1864, which affects
      nucleotide binding and inhibits Rac1 activity, concentration-dependently
      inhibited the contractile responses induced by several different modes of
      activation (high-K+, phenylephrine, carbachol and protein kinase C activation by
      phorbol-12,13-dibutyrate) in several different visceral (urinary bladder, ileum)
      and vascular (mesenteric artery, saphenous artery, aorta) smooth muscle tissues.
      This contractile inhibition was associated with inhibition of the Ca2+ transient.
      Knockout of Rac1 (with a 50% loss of Rac1 protein) lowered active stress in the
      urinary bladder and the saphenous artery consistent with a role of Rac1 in
      facilitating smooth muscle contraction. NSC23766, which blocks interaction
      between Rac1 and some guanine nucleotide exchange factors, specifically inhibited
      the alpha1 receptor responses (phenylephrine) in vascular tissues and potentiated
      prostaglandin F2alpha and thromboxane (U46619) receptor responses. The latter
      potentiating effect occurred at lowered intracellular [Ca2+]. These results show
      that Rac1 activity is required for active contraction in smooth muscle, probably
      via enabling an adequate Ca2+ transient. At the same time, specific agonists
      recruit Rac1 signalling via upstream modulators, resulting in either a
      potentiation of contraction via Ca2+ mobilization (alpha1 receptor stimulation)
      or an attenuated contraction via inhibition of Ca2+ sensitization (prostaglandin
      and thromboxane receptors).

PMID- 24297855
TI  - [Air pollution and asthma in childhood].
AB  - Exposure to outdoor air pollutants and passive tobacco smoke are common but
      avoidable worldwide risk factors for morbidity and mortality of individuals. In
      addition to well-known effects of pollutants on the cardiovascular system and the
      development of cancer, in recent years the association between air pollution and
      respiratory morbidity has become increasingly apparent. Not only in adults, but
      also in children with asthma and in healthy children a clear harmful effect of
      exposure towards air pollutants has been demonstrated in many studies. Among
      others increased pollution has been shown to result in more frequent and more
      severe respiratory symptoms, more frequent exacerbations, higher need for asthma
      medication, poorer lung function and increased visits to the emergency department
      and more frequent hospitalisations. While these associations are well
      established, the available data on the role of air pollution in the development
      of asthma seems less clear. Some studies have shown that increased exposure
      towards tobacco smoke and air pollution leads to an increase in asthma incidence
      and prevalence; others were not able to confirm those findings. Possible reasons
      for this discrepancy are different definitions of the outcome asthma, different
      methods for exposure estimation and differences in the populations studied with
      differing underlying genetic backgrounds. Regardless of this inconsistency,
      several mechanisms have already been identified linking air pollution with asthma
      development. Among these are impaired lung growth and development, immunological
      changes, genetic or epigenetic effects or increased predisposition for allergic
      sensitisation. What the exact interactions are and which asthmatic phenotypes
      will be influenced most by pollutants will be shown by future studies. This
      knowledge will then be helpful in exploring possible preventive measures for the
      individual and to help policy makers in deciding upon most appropriate
      regulations on a population level. 

PMID- 24297856
TI  - [The role of the microbial environment for the development of childhood asthma
      and allergies].
AB  - Asthma and allergies are among the most frequent chronic diseases in childhood.
      Their prevalence has increased during the second half of the twentieth century
      but seem to stabilize in recent years in many Western European countries such as
      Switzerland. Although the genetic background is known to have a strong impact on
      an individual's risk to develop asthma or allergy it seems likely that
      environmental factors are mostly responsible for the increase in prevalence over
      time. Much research has been devoted to environmental risk factors promoting the
      development of asthma and allergies. Yet, there is increasing interest in
      environmental factors which might protect from the development of these diseases
      and which might have been reduced along with the development of a "Western
      lifestyle". The role of environmental allergens, the hygiene hypothesis and the
      role of the farm environment on the development of asthma and allergies are
      discussed. An emphasis is put on the microbial environment as encountered in the
      farming environment which has been shown to confer protection from the
      development of asthma and allergies. It is likely that among other factors the
      development of a "Western lifestyle" went along with a marked change of the
      microbial environment children are exposed to. 

PMID- 24297857
TI  - [Health effects of environmental noise exposure].
AB  - In the EU 27 countries about 100 million persons are exposed to road traffic
      noise above 55 dB (LDEN) according to the European Environment Agency. Exposure
      to railway noise affects 16 million individuals, aircraft noise 4 million and
      industry noise 1 million persons. Although the proportion of people reporting to
      be annoyed by noise exposure is substantial, health effects of noise is rarely an
      issue in general practitioners' consultations. According to stress models chronic
      noise exposure results in an increased allostatic load by direct physiological
      responses as well as psychological stress responses including sleep disturbances.
      In relation to acute and chronic noise exposure an increase of blood pressure was
      observed in epidemiological studies. An association between ischemic heart
      diseases and noise exposure was observed in various studies. However, the data is
      less consistent for other cardiovascular diseases and for cognitive effects in
      children. The association between metabolic syndrome and noise has rarely been
      investigated so far. Recently an association between road traffic noise and
      diabetes was observed in a Danish cohort study. Given the plausibility for a
      noise effect, general practitioners should consider noise exposure in patients
      with increased cardiometabolic risk. 

PMID- 24297859
TI  - [Health effects of electromagnetic fields].
AB  - Use of electricity causes extremely low frequency magnetic fields (ELF-MF) and
      wireless communication devices emit radiofrequency electromagnetic fields (RF
      EMF). Average ELF-MF exposure is mainly determined by high voltage power lines
      and transformers at home or at the workplace, whereas RF-EMF exposure is mainly
      caused by devices operating close to the body (mainly mobile and cordless
      phones). Health effects of EMF are controversially discussed. The IARC classified
      ELF-MF and RF-EMF as possible carcinogenic. Most consistent epidemiological
      evidence was found for an association between ELF-MF and childhood leukaemia. If
      causal, 1 - 4 percent of all childhood leukaemia cases could be attributed to ELF
      MF. Epidemiological research provided some indications for an association between
      ELF-MF and Alzheimer's diseases as well as amyotrophic lateral sclerosis,
      although not entirely consistent. Regarding mobile phones and brain tumours, some
      studies observed an increased risk after heavy or long term use on the one hand.
      On the other hand, brain tumour incidence was not found to have increased in the
      last decade in Sweden, England or the US. Acute effects of RF-EMF on non-specific
      symptoms of ill health seem unlikely according to randomized and double blind
      provocation studies. However, epidemiological research on long term effects is
      still limited. Although from the current state of the scientific knowledge a
      large individual health risk from RF-EMF exposure is unlikely, even a small risk
      would have substantial public health relevance because of the widespread use of
      wireless communication technologies. 

PMID- 24297858
TI  - [Air pollution and health - counselling options for physicians].
AB  - While air quality is usually an environmental condition patients can little do
      about, there are a few options and decisions that modify the personal exposure
      and risk. Location - in particular the residence - time and activity are the key
      determinants of personal exposure. Traffic-related primary pollutants such as
      ultrafine particles or diesel soot are highly concentrated along busy roads but
      reach urban background concentrations already some 100 - 200 meters off.
      Morbidity and mortality follow this spatial pattern, which is usually attributed
      to these pollutants. Depending on ventilation systems, indoor exposure can be
      substantially lower. Studies done in China confirm that the use of face masks in
      extremely polluted cities can reduce exposure, resulting in lower inflammatory
      and cardiovascular responses. A diet rich in antioxidants appears to also reduce
      some of the oxidative and inflammatory effects of air pollution and treatments
      such as leucotrien receptor antagonists or statins pay interfere with some of the
      adverse effects of pollution. However, the benefits, if any, are unlikely to be
      large. A quantitative comparison of the various pollution related health effects 
      namely from smoking, passive smoking and air pollution - reveal a typical
      paradox to be well understood: the individual risks related to air pollution and
      that one may reduce through personal decisions are rather small. However, given
      the large number of people exposed (i. e. in essence the entire population), the
      overall air pollution related health burden is rather substantial. This
      underscores that sustained clean air policies are indeed the most important and
      efficient solution to reduce the air pollution related health effects. 

PMID- 24297860
TI  - [Environmental medicine counselling in daily medical practice].
AB  - Since 2008, the Swiss Society of Doctors for the Environment runs a small
      interdisciplinary environmental medicine counselling structure for patients with
      complaints attributed to environmental exposures. The model is embedded in
      everyday practice with a central coordination and consultation office as well as
      a network of general practitioners interested in environmental medicine who make
      environmental medical assessments and consultations based on a standardised
      protocol in their practices. If necessary, environmental experts are consulted
      and home investigations are conducted. An evaluation study concluded that this
      model is feasible and addresses an existing need. The assessment option is
      experienced as helpful by patients. The interdisciplinary collaboration with
      environmental experts has proved to be effective. The aim of the assessment is to
      detect or to rule out common diseases and to analyse the impact of suspected
      environmental burden on the complaints in order to find individual therapeutic
      approaches. The progression of common medical and psychiatric illnesses can be
      negatively affected by environmental influences, too. The main instrument of the
      assessment is an extensive medical and psycho-social history with an additional
      environmental history including a systematic questionnaire and environmental key
      questions. Close collaboration with the family doctor is crucial. Assessment
      steps can be streamlined and consultation suggestions can be embedded in the
      family doctors holistic and lasting concept of treatment. Where possible our
      society gladly provides family doctors with our practical environment-related
      expertise. It is an important concern for us to make environmental medicine an
      integral part of primary care, also in the process of informing the patient about
      the prevention of and precautions against harmful or potentially harmful
      environmental burdens. We hope that the experiences made in our project will
      contribute to this goal. 

PMID- 24297861
TI  - [Update - health risks induced by ionizing radiation from diagnostic imaging].
AB  - Ionizing radiation is the most thoroughly investigated exogenous noxa. Since the
      early 20th century it is well known that using ionizing radiation in diagnostic
      procedures causes cancer - physicians themselves frequently being struck by this
      disease in those early days of radiology. Radiation protection therefore plays an
      important role. Below doses of 100 Millisievert (mSv) however much research has
      to be accomplished yet because not only malignant tumors, but cardiovascular
      diseases, malformations and genetic sequelae attributable to low dose radiation
      have been described. Unborns, children and adolescents are highly vulnerable.
      Dose response correlations are subject to continuing discussions because data
      stem mostly from calculations studying Japanese atomic bomb survivors. Radiation
      exposure is not exactly known, and it is unknown, if observations of radiation
      induced diseases in this ethnicity can be generalized. Nowadays the main source
      of low dose ionizing radiation from medical diagnostics is due to
      computertomography (CT). Large recent clinical studies from the UK and Australia
      investigating cancer incidence after exposition to CT in childhood and
      adolescence confirm that low doses in the range of 5 mSv already significantly
      increase the risk of malignant diseases during follow up. Imaging techniques as
      ultrasound and magnetic resonance tomography therefore should be preferred
      whenever appropriate. 

PMID- 24297862
TI  - Reducing TNF receptor 2+ regulatory T cells via the combined action of
      azacitidine and the HDAC inhibitor, panobinostat for clinical benefit in acute
      myeloid leukemia patients.
AB  - PURPOSE: Acute myeloid leukemia (AML) provides an environment that enables immune
      suppression, resulting in functionally defective effector T cells; regulatory T
      cells (Treg) are significant contributors to the impaired antitumor immune
      response. As TNF is present at high levels in AML and TNF receptor-2 (TNFR2)
      expressing Tregs identify highly functional Tregs, we examine the hypothesis that
      TNFR2(+) Tregs are a relevant Treg subset in this cancer. We also determine the
      effect of the novel combinatorial therapy of the demethylating agent, azacitidine
      with the histone deacetylase inhibitor, panobinostat on Tregs, particularly
      TNFR2(+) Tregs. EXPERIMENTAL DESIGN: Thirty healthy donors and 14 patients with
      AML were enrolled in this study. Patients were treated with azacitidine and
      panobinostat for 28-day cycles. The frequency and functional relevance of
      TNFR2(+) Tregs were analyzed subsequently. RESULTS: We report that TNFR2(+) Tregs
      are increased in AML and have a high migration potential toward the bone marrow.
      Furthermore, we demonstrate that the level of TNFR2(+) Tregs in the peripheral
      blood and the bone marrow of patients are decreased in vivo after exposure to
      panobinostat and azacitidine. Reductions in TNFR2(+) Tregs were associated with
      increases in Interferon (IFN)-gamma and interleukin (IL)-2 production by effector
      T cells within the bone marrow and beneficial clinical responses. In vitro
      mechanistic studies indicated panobinostat as the primary driver for the
      reduction of Tregs. CONCLUSIONS: Our study provides for the first time, in vivo
      validation of the ability of panobinostat in combination with azacitidine to
      suppress prevalent TNFR2(+) Tregs, resulting in clinical benefits within patients
      with AML.

PMID- 24297863
TI  - BET bromodomain inhibition of MYC-amplified medulloblastoma.
AB  - PURPOSE: MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and
      extraterminal (BET) bromodomain inhibition has recently been shown to suppress
      MYC-associated transcriptional activity in other cancers. The compound JQ1
      inhibits BET bromodomain-containing proteins, including BRD4. Here, we
      investigate BET bromodomain targeting for the treatment of MYC-amplified
      medulloblastoma. EXPERIMENTAL DESIGN: We evaluated the effects of genetic and
      pharmacologic inhibition of BET bromodomains on proliferation, cell cycle, and
      apoptosis in established and newly generated patient- and genetically engineered
      mouse model (GEMM)-derived medulloblastoma cell lines and xenografts that
      harbored amplifications of MYC or MYCN. We also assessed the effect of JQ1 on MYC
      expression and global MYC-associated transcriptional activity. We assessed the in
      vivo efficacy of JQ1 in orthotopic xenografts established in immunocompromised
      mice. RESULTS: Treatment of MYC-amplified medulloblastoma cells with JQ1
      decreased cell viability associated with arrest at G1 and apoptosis. We observed
      downregulation of MYC expression and confirmed the inhibition of MYC-associated
      transcriptional targets. The exogenous expression of MYC from a retroviral
      promoter reduced the effect of JQ1 on cell viability, suggesting that attenuated
      levels of MYC contribute to the functional effects of JQ1. JQ1 significantly
      prolonged the survival of orthotopic xenograft models of MYC-amplified
      medulloblastoma (P < 0.001). Xenografts harvested from mice after five doses of
      JQ1 had reduced the expression of MYC mRNA and a reduced proliferative index.
      CONCLUSION: JQ1 suppresses MYC expression and MYC-associated transcriptional
      activity in medulloblastomas, resulting in an overall decrease in medulloblastoma
      cell viability. These preclinical findings highlight the promise of BET
      bromodomain inhibitors as novel agents for MYC-amplified medulloblastoma.

PMID- 24297864
TI  - HIF-1alpha of bone marrow endothelial cells implies relapse and drug resistance
      in patients with multiple myeloma and may act as a therapeutic target.
AB  - PURPOSE: To investigate the role of hypoxia-inducible factor-1alpha (HIF-1alpha)
      in angiogenesis and drug resistance of bone marrow endothelial cells of patients
      with multiple myeloma. EXPERIMENTAL DESIGN: HIF-1alpha mRNA and protein were
      evaluated in patients with multiple myeloma endothelial cells (MMEC) at
      diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on
      refractory phase to these drugs, at remission; in endothelial cells of patients
      with monoclonal gammapathies of undetermined significance (MGUS; MGECs), and of
      those with benign anemia (controls). The effects of HIF-1alpha inhibition by
      siRNA or panobinostat (an indirect HIF-1alpha inhibitor) on the expression of HIF
      1alpha proangiogenic targets, on MMEC angiogenic activities in vitro and in vivo,
      and on overcoming MMEC resistance to bortezomib and lenalidomide were studied.
      The overall survival of the patients was also observed. RESULTS: Compared with
      the other endothelial cell types, only MMECs from 45% of relapsed/refractory
      patients showed a normoxic HIF-1alpha protein stabilization and activation that
      were induced by reactive oxygen species (ROS). The HIF-1alpha protein correlated
      with the expression of its proangiogenic targets. The HIF-1alpha inhibition by
      either siRNA or panobinostat impaired the MMECs angiogenesis-related functions
      both in vitro and in vivo and restored MMEC sensitivity to bortezomib and
      lenalidomide. Patients with MMECs expressing the HIF-1alpha protein had shorter
      overall survival. CONCLUSIONS: The HIF-1alpha protein in MMECs may induce
      angiogenesis and resistance to bortezomib and lenalidomide and may be a plausible
      target for the antiangiogenic management of patients with well-defined
      relapsed/refractory multiple myeloma. It may also have prognostic significance.

PMID- 24297865
TI  - Aligning medication reconciliation and secure messaging: qualitative study of
      primary care providers' perspectives.
AB  - BACKGROUND: Virtual (non-face-to-face) medication reconciliation strategies may
      reduce adverse drug events (ADEs) among vulnerable ambulatory patients.
      Understanding provider perspectives on the use of technology for medication
      reconciliation can inform the design of patient-centered solutions to improve
      ambulatory medication safety. OBJECTIVE: The aim of the study was to describe
      primary care providers' experiences of ambulatory medication reconciliation and
      secure messaging (secure email between patients and providers), and to elicit
      perceptions of a virtual medication reconciliation system using secure messaging
      (SM). METHODS: This was a qualitative study using semi-structured interviews.
      From January 2012 to May 2012, we conducted structured observations of primary
      care clinical activities and interviewed 15 primary care providers within a
      Veterans Affairs Healthcare System in Boston, Massachusetts (USA). We carried out
      content analysis informed by the grounded theory. RESULTS: Of the 15
      participating providers, 12 were female and 11 saw 10 or fewer patients in a
      typical workday. Experiences and perceptions elicited from providers during in
      depth interviews were organized into 12 overarching themes: 4 themes for
      experiences with medication reconciliation, 3 themes for perceptions on how to
      improve ambulatory medication reconciliation, and 5 themes for experiences with
      SM. Providers generally recognized medication reconciliation as a valuable
      component of primary care delivery and all agreed that medication reconciliation
      following hospital discharge is a key priority. Most providers favored delegating
      the responsibility for medication reconciliation to another member of the staff,
      such as a nurse or a pharmacist. The 4 themes related to ambulatory medication
      reconciliation were (1) the approach to complex patients, (2) the effectiveness
      of medication reconciliation in preventing ADEs, (3) challenges to completing
      medication reconciliation, and (4) medication reconciliation during transitions
      of care. Specifically, providers emphasized the importance of medication
      reconciliation at the post-hospital visit. Providers indicated that assistance
      from a caregiver (eg, a family member) for medication reconciliation was helpful
      for complex or elderly patients and that patients' social or cognitive factors
      often made medication reconciliation challenging. Regarding providers' use of SM,
      about half reported using SM frequently, but all felt that it improved their
      clinical workflow and nearly all providers were enthusiastic about a virtual
      medication reconciliation system, such as one using SM. All providers thought
      that such a system could reduce ADEs. CONCLUSIONS: Although providers recognize
      the importance and value of ambulatory medication reconciliation, various factors
      make it difficult to execute this task effectively, particularly among complex or
      elderly patients and patients with complicated social circumstances. Many
      providers favor enlisting the support of pharmacists or nurses to perform
      medication reconciliation in the outpatient setting. In general, providers are
      enthusiastic about the prospect of using secure messaging for medication
      reconciliation, particularly during transitions of care, and believe a system of
      virtual medication reconciliation could reduce ADEs.

PMID- 24297866
TI  - Altered expression of platelet proteins and calpain activity mediate hypoxia
      induced prothrombotic phenotype.
AB  - Oxygen-compromised environments, such as high altitude, air travel, and sports,
      and pathological conditions, such as solid tumors, have been suggested to be
      prothrombotic. Despite the indispensable role of platelets in thrombus formation,
      the studies linking hypoxia, platelet reactivity, and thrombus formation are
      limited. In the present study, platelet proteome/reactivity was analyzed to
      elucidate the acute hypoxia-induced prothrombotic phenotype. Rats exposed to
      acute simulated hypoxia (282 torr/8% oxygen) demonstrated a decreased bleeding
      propensity and increased platelet reactivity. Proteomic analysis of hypoxic
      platelets revealed 27 differentially expressed proteins, including those involved
      in coagulation. Among these proteins, calpain small subunit 1, a 28-kDa
      regulatory component for calpain function, was significantly upregulated under
      hypoxic conditions. Moreover, intraplatelet Ca(2+) level and platelet calpain
      activity were also found to be in accordance with calpain small subunit 1
      expression. The inhibition of calpain activity demonstrated reversal of hypoxia
      induced platelet hyperreactivity. The prothrombotic role for calpain was further
      confirmed by an in vivo model of hypoxia-induced thrombosis. Interestingly,
      patients who developed thrombosis while at extreme altitude had elevated plasma
      calpain activities and increased soluble P-selectin level. In summary, this study
      suggests that augmented calpain activity is associated with increased incidence
      of thrombosis under hypoxic environments. 

PMID- 24297867
TI  - Suboptimal dosing of rituximab in male and female patients with DLBCL.
AB  - To determine the effect of gender on outcome, the male hazard ratio for
      progression-free survival (HRPFS-male) was determined in patients with diffuse
      large B-cell lymphoma (DLBCL). In young patients (MapThera International Trial
      study), HRPFS-male was 1.3 (P = .092) without and 1.1 (P = .660) with rituximab.
      In elderly patients (RICOVER-60 study), HRPFS-male was 1.1 (P = .348) with CHOP
      but increased to 1.6 (P = .004) with R-CHOP. The similar improvements of outcome
      in young patients were associated with similar rituximab clearances in young
      males and females (9.89 vs 10.38 mL/h; P = .238), whereas the greater benefit for
      elderly females was associated with a slower rituximab clearance (8.47 vs 10.59
      mL/h; P = .005) and hence higher serum levels and longer exposure times,
      attributable to an age-dependent (P = .004) decrease of rituximab clearance in
      females but not males. Compared with elderly females, all other subgroups had
      significantly faster rituximab clearances and hence appear to be suboptimally
      dosed when rituximab is given at 375 mg/m(2). Although early results of
      pharmacokinetic-based prospective trials designed to exploit the full therapeutic
      potential of rituximab suggest that increased doses and/or prolonged exposure
      times can improve the outcome of elderly males with DLBCL, further studies are
      warranted that address the optimization of rituximab dose and schedule in all
      subgroups of DLBCL patients. 

PMID- 24297868
TI  - Early assessment of minimal residual disease identifies patients at very high
      relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma.
AB  - Detection of minimal disseminated disease (MDD) at diagnosis correlates with
      relapse risk in children with anaplastic lymphoma kinase (ALK)-positive
      anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual
      disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies
      patients at the highest relapse risk. Blood and/or bone marrow of 180 patients
      with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Munster-type protocols
      were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD
      positive. MRD before the second therapy course could be evaluated in 52 MDD
      positive patients. MRD positivity correlated with uncommon histology. The
      cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients
      (81% +/- 8%) was significantly higher than the CIR of 26 MDD-positive/MRD
      negative (31% +/- 9%) and 77 MDD-negative patients (15% +/- 5%) (P < .001). Five
      year survival of MDD-negative and MDD-positive/MRD-negative patients was 91% +/-
      3% and 92% +/- 5%, respectively, compared with 65% +/- 9% of MDD-positive/MRD
      positive patients (P < .001). Early evaluation of MRD in NPM-ALK-positive ALCL
      identifies patients with a very high relapse risk and inferior survival. 

PMID- 24297869
TI  - A cellular system for quantitation of vitamin K cycle activity: structure
      activity effects on vitamin K antagonism by warfarin metabolites.
AB  - Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR)
      by depleting reduced vitamin K that is required for posttranslational
      modification of vitamin K-dependent clotting factors. In vitro prediction of the
      in vivo potency of vitamin K antagonists is complicated by the complex
      multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay
      that enables quantitative analysis of gamma-glutamyl carboxylation and its
      antagonism in live cells. We engineered a human embryonic kidney (HEK) 293
      derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising
      the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of
      proline-rich Gla protein 2. Maximal gamma-glutamyl carboxylation of F9CH required
      vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin
      at a physiologically relevant concentration. Cellular gamma-glutamyl
      carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers
      (S > R) consistent with their in vivo potencies. We further analyzed the
      structure-activity relationship for inhibition of gamma-glutamyl carboxylation by
      warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and
      especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus.
      After correction for in vivo concentration and protein binding, 10
      hydroxywarfarin and warfarin alcohols were predicted to be the most potent
      inhibitory metabolites in vivo. 

PMID- 24297870
TI  - RUNX1 and NF-E2 upregulation is not specific for MPNs, but is seen in
      polycythemic disorders with augmented HIF signaling.
AB  - Overexpression of transcription factors runt-related transcription factor 1
      (RUNX1) and nuclear factor, erythroid-derived 2 (NF-E2) was reported in
      granulocytes of patients with polycythemia vera and other myeloproliferative
      neoplasms (MPNs). Further, a transgenic mouse overexpressing the NF-E2 transgene
      was reported to be a model of MPN. We hypothesized that increased transcripts of
      RUNX1 and NF-E2 might characterize other polycythemic states with primary
      polycythemic features, that is, those with exaggerated erythropoiesis due to
      augmented erythropoietin (EPO) sensitivity. We tested the expression of RUNX1 and
      NF-E2 in polycythemic patients of diverse phenotypes and molecular causes. We
      report that RUNX1 and NF-E2 overexpression is not specific for MPN; these
      transcripts were also significantly elevated in polycythemias with augmented
      hypoxia-inducible factor activity whose erythroid progenitors were hypersensitive
      to EPO. RUNX1 and NF-E2 overexpression was not detected in patients with EPO
      receptor (EPOR) gain-of-function, suggesting distinct mechanisms by which
      erythroid progenitors in polycythemias with defects of hypoxia sensing and EPOR
      mutations exert their EPO hypersensitivity. 

PMID- 24297871
TI  - Activated mouse eosinophils protect against lethal respiratory virus infection.
AB  - Eosinophils are recruited to the airways as a prominent feature of the asthmatic
      inflammatory response where they are broadly perceived as promoting
      pathophysiology. Respiratory virus infections exacerbate established asthma;
      however, the role of eosinophils and the nature of their interactions with
      respiratory viruses remain uncertain. To explore these questions, we established
      acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3
      distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found
      that eosinophils recruited to the airways of otherwise naive mice in response to
      Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are
      activated by and degranulate specifically in response to PVM infection.
      Furthermore, we demonstrate that activated eosinophils from both Aspergillus
      antigen and cytokine-driven asthma models are profoundly antiviral and promote
      survival in response to an otherwise lethal PVM infection. Thus, although
      activated eosinophils within a Th2-polarized inflammatory response may have
      pathophysiologic features, they are also efficient and effective mediators of
      antiviral host defense. 

PMID- 24297872
TI  - A systematic analysis of global anemia burden from 1990 to 2010.
AB  - Previous studies of anemia epidemiology have been geographically limited with
      little detail about severity or etiology. Using publicly available data, we
      estimated mild, moderate, and severe anemia from 1990 to 2010 for 187 countries,
      both sexes, and 20 age groups. We then performed cause-specific attribution to 17
      conditions using data from the Global Burden of Diseases, Injuries and Risk
      Factors (GBD) 2010 Study. Global anemia prevalence in 2010 was 32.9%, causing
      68.36 (95% uncertainty interval [UI], 40.98 to 107.54) million years lived with
      disability (8.8% of total for all conditions [95% UI, 6.3% to 11.7%]). Prevalence
      dropped for both sexes from 1990 to 2010, although more for males. Prevalence in
      females was higher in most regions and age groups. South Asia and Central, West,
      and East sub-Saharan Africa had the highest burden, while East, Southeast, and
      South Asia saw the greatest reductions. Iron-deficiency anemia was the top cause
      globally, although 10 different conditions were among the top 3 in regional
      rankings. Malaria, schistosomiasis, and chronic kidney disease-related anemia
      were the only conditions to increase in prevalence. Hemoglobinopathies made
      significant contributions in most populations. Burden was highest in children
      under age 5, the only age groups with negative trends from 1990 to 2010. 

PMID- 24297873
TI  - A prospective natural history study of quitting or reducing gambling with or
      without treatment: protocol.
AB  - BACKGROUND: Only a small percentage of gamblers ever seek treatment, often due to
      stigma, embarrassment, or a desire to handle their problems on their own. While
      the majority of pathological gamblers who achieve remittance do so without
      accessing formal treatment, factors related to successful resolution have not
      been thoroughly explored. OBJECTIVE: Employing a prospective natural history
      design, the study will therefore undertake an investigation to explore life
      events, motivating factors, and strategies used by problem gamblers to quit or
      reduce their gambling without formal treatment. METHODS: Prospective participants
      (19 years or older) currently gambling at problematic levels with strong
      intentions toward quitting gambling will be directed to fill out a Web-based
      survey. Eligible participants will subsequently complete a survey that will
      assess: (1) types, frequency, and amount of money spent on gambling, (2) life
      events experienced in the past 12 months, (3) level of autonomous motivation for
      change, and (4) use of treatment services. Every 3 months for the duration of one
      year following the completion of their baseline survey, participants will be sent
      an email notification requesting them to complete a follow-up survey similar in
      content to the baseline survey. The four surveys will assess whether participants
      have experienced changes in their gambling behaviors along with positive or
      negative life events and motivations for change since the last survey.
      Individuals who are in the action and maintenance stages of quitting gambling at
      follow-up will be also asked about their techniques and strategies used to quit
      or reduce gambling. At 18 months post baseline, participants will be asked to
      complete a fifth and final follow-up survey that will also assess whether
      participants have experienced any barriers to change and whether they resolved
      their gambling to low risk levels. RESULTS: The study has commenced in May 2013
      and is currently in the recruitment stage. The study is scheduled to conclude in
      2016. CONCLUSIONS: As this study will examine the active ingredients in natural
      recovery from gambling problems, the results will inform ways of promoting change
      among the large number of problem gamblers who do not seek treatment as well as
      improve treatment for those who do seek help. The information gained will also be
      useful in identifying effective self-help strategies for those who face
      challenges in accessing treatment, may be incorporated in standard treatment,
      provide brief intervention techniques, as well as inform relapse prevention
      strategies.

PMID- 24297874
TI  - Resolving the roles of immunity, pathogenesis, and immigration for rabies
      persistence in vampire bats.
AB  - Bats are important reservoirs for emerging infectious diseases, yet the
      mechanisms that allow highly virulent pathogens to persist within bat populations
      remain obscure. In Latin America, vampire-bat-transmitted rabies virus represents
      a key example of how such uncertainty can impede efforts to prevent cross-species
      transmission. Despite decades of agricultural and human health losses, control
      efforts have had limited success. To establish persistence mechanisms of vampire
      bat-transmitted rabies virus in Latin America, we use data from a spatially
      replicated, longitudinal field study of vampire bats in Peru to parameterize a
      series of mechanistic transmission models. We find that single-colony persistence
      cannot occur. Instead, dispersal of bats between colonies, combined with a high
      frequency of immunizing nonlethal infections, is necessary to maintain rabies
      virus at levels consistent with field observations. Simulations show that the
      strong spatial component to transmission dynamics could explain the failure of
      bat culls to eliminate rabies and suggests that geographic coordination of
      control efforts might reduce transmission to humans and domestic animals. These
      findings offer spatial dynamics as a mechanism for rabies persistence in bats
      that might be important for the understanding and control of other bat-borne
      pathogens. 

PMID- 24297875
TI  - NAL1 allele from a rice landrace greatly increases yield in modern indica
      cultivars.
AB  - Increasing crop production is essential for securing the future food supply in
      developing countries in Asia and Africa as economies and populations grow.
      However, although the Green Revolution led to increased grain production in the
      1960s, no major advances have been made in increasing yield potential in rice
      since then. In this study, we identified a gene, SPIKELET NUMBER (SPIKE), from a
      tropical japonica rice landrace that enhances the grain productivity of indica
      cultivars through pleiotropic effects on plant architecture. Map-based cloning
      revealed that SPIKE was identical to NARROW LEAF1 (NAL1), which has been reported
      to control vein pattern in leaf. Phenotypic analyses of a near-isogenic line of a
      popular indica cultivar, IR64, and overexpressor lines revealed increases in
      spikelet number, leaf size, root system, and the number of vascular bundles,
      indicating the enhancement of source size and translocation capacity as well as
      sink size. The near-isogenic line achieved 13-36% yield increase without any
      negative effect on grain appearance. Expression analysis revealed that the gene
      was expressed in all cell types: panicles, leaves, roots, and culms supporting
      the pleiotropic effects on plant architecture. Furthermore, SPIKE increased grain
      yield by 18% in the recently released indica cultivar IRRI146, and increased
      spikelet number in the genetic background of other popular indica cultivars. The
      use of SPIKE in rice breeding could contribute to food security in indica-growing
      regions such as South and Southeast Asia. 

PMID- 24297876
TI  - Mantle-slab interaction and redox mechanism of diamond formation.
AB  - Subduction tectonics imposes an important role in the evolution of the interior
      of the Earth and its global carbon cycle; however, the mechanism of the mantle
      slab interaction remains unclear. Here, we demonstrate the results of high
      pressure redox-gradient experiments on the interactions between Mg-Ca-carbonate
      and metallic iron, modeling the processes at the mantle-slab boundary; thereby,
      we present mechanisms of diamond formation both ahead of and behind the redox
      front. It is determined that, at oxidized conditions, a low-temperature Ca-rich
      carbonate melt is generated. This melt acts as both the carbon source and
      crystallization medium for diamond, whereas at reduced conditions, diamond
      crystallizes only from the Fe-C melt. The redox mechanism revealed in this study
      is used to explain the contrasting heterogeneity of natural diamonds, as seen in
      the composition of inclusions, carbon isotopic composition, and nitrogen impurity
      content. 

PMID- 24297877
TI  - Edentulism, beaks, and biomechanical innovations in the evolution of theropod
      dinosaurs.
AB  - Maniraptoriformes, the speciose group of derived theropod dinosaurs that
      ultimately gave rise to modern birds, display a diverse and remarkable suite of
      skeletal adaptations. Apart from the evolution of flight, a large-scale change in
      dietary behavior appears to have been one of the main triggers for
      specializations in the bauplan of these derived theropods. Among the different
      skeletal specializations, partial or even complete edentulism and the development
      of keratinous beaks form a recurring and persistent trend in from the evolution
      of derived nonavian dinosaurs. Therizinosauria is an enigmatic maniraptoriform
      clade, whose members display these and other osteological characters thought to
      be correlated with the shift from carnivory to herbivory. This makes
      therizinosaurians prime candidates to assess the functional significance of these
      morphological characters. Based on a highly detailed biomechanical model of
      Erlikosaurus andrewsi, a therizinosaurid from the Upper Cretaceous of Mongolia,
      different morphological configurations incorporating soft-tissue structures, such
      as a keratinous rhamphotheca, are evaluated for their biomechanical performance.
      Our results indicate that the development of beaks and the presence of a
      keratinous rhamphotheca would have helped to dissipate stress and strain, making
      the rostral part of the skull less susceptible to bending and displacement, and
      this benefit may extend to other vertebrate clades that possess rhamphothecae.
      Keratinous beaks, paralleled by edentulism, thus represent an evolutionary
      innovation developed early in derived theropods to enhance cranial stability,
      distinct to postulated mass-saving benefits associated with the origin of flight.

PMID- 24297879
TI  - Profile of Barbara Imperiali.

PMID- 24297878
TI  - Pentameric complex of viral glycoprotein H is the primary target for potent
      neutralization by a human cytomegalovirus vaccine.
AB  - Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant
      patients, and congenital HCMV infection can lead to birth defects. Developing an
      effective HCMV vaccine is a high medical priority. One of the challenges to the
      efforts has been our limited understanding of the viral antigens important for
      protective antibodies. Receptor-mediated viral entry to endothelial/epithelial
      cells requires a glycoprotein H (gH) complex comprising five viral proteins (gH,
      gL, UL128, UL130, and UL131). This gH complex is notably missing from HCMV
      laboratory strains as well as HCMV vaccines previously evaluated in the clinic.
      To support a unique vaccine concept based on the pentameric gH complex, we
      established a panel of 45 monoclonal antibodies (mAbs) from a rabbit immunized
      with an experimental vaccine virus in which the expression of the pentameric gH
      complex was restored. Over one-half (25 of 45) of the mAbs have neutralizing
      activity. Interestingly, affinity for an antibody to bind virions was not
      correlated with its ability to neutralize the virus. Genetic analysis of the 45
      mAbs based on their heavy- and light-chain sequences identified at least 26 B
      cell linage groups characterized by distinct binding or neutralizing properties.
      Moreover, neutralizing antibodies possessed longer complementarity-determining
      region 3 for both heavy and light chains than those with no neutralizing
      activity. Importantly, potent neutralizing mAbs reacted to the pentameric gH
      complex but not to gB. Thus, the pentameric gH complex is the primary target for
      antiviral antibodies by vaccination. 

PMID- 24297880
TI  - Sensitivity to ocean acidification parallels natural pCO2 gradients experienced
      by Arctic copepods under winter sea ice.
AB  - The Arctic Ocean already experiences areas of low pH and high CO2, and it is
      expected to be most rapidly affected by future ocean acidification (OA). Copepods
      comprise the dominant Arctic zooplankton; hence, their responses to OA have
      important implications for Arctic ecosystems, yet there is little data on their
      current under-ice winter ecology on which to base future monitoring or make
      predictions about climate-induced change. Here, we report results from Arctic
      under-ice investigations of copepod natural distributions associated with late
      winter carbonate chemistry environmental data and their response to manipulated
      pCO2 conditions (OA exposures). Our data reveal that species and life stage
      sensitivities to manipulated OA conditions were correlated with their vertical
      migration behavior and with their natural exposures to different pCO2 ranges.
      Vertically migrating adult Calanus spp. crossed a pCO2 range of >140 MUatm daily
      and showed only minor responses to manipulated high CO2. Oithona similis, which
      remained in the surface waters and experienced a pCO2 range of <75 MUatm, showed
      significantly reduced adult and nauplii survival in high CO2 experiments. These
      results support the relatively untested hypothesis that the natural range of pCO2
      experienced by an organism determines its sensitivity to future OA and highlight
      that the globally important copepod species, Oithona spp., may be more sensitive
      to future high pCO2 conditions compared with the more widely studied larger
      copepods. 

PMID- 24297881
TI  - Mechanistic characterization and crystal structure of a small molecule
      inactivator bound to plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease
      inhibitor (serpin) family. Excessive PAI-1 activity is associated with human
      disease, making it an attractive pharmaceutical target. However, like other
      serpins, PAI-1 has a labile structure, making it a difficult target for the
      development of small molecule inhibitors, and to date, there are no US Food and
      Drug Administration-approved small molecule inactivators of any serpins. Here we
      describe the mechanistic and structural characterization of a high affinity
      inactivator of PAI-1. This molecule binds to PAI-1 reversibly and acts through an
      allosteric mechanism that inhibits PAI-1 binding to proteases and to its cofactor
      vitronectin. The binding site is identified by X-ray crystallography and
      mutagenesis as a pocket at the interface of beta-sheets B and C and alpha-helix
      H. A similar pocket is present on other serpins, suggesting that this site could
      be a common target in this structurally conserved protein family. 

PMID- 24297882
TI  - Eating up the world's food web and the human trophic level.
AB  - Trophic levels are critical for synthesizing species' diets, depicting energy
      pathways, understanding food web dynamics and ecosystem functioning, and
      monitoring ecosystem health. Specifically, trophic levels describe the position
      of species in a food web, from primary producers to apex predators (range, 1-5).
      Small differences in trophic level can reflect large differences in diet.
      Although trophic levels are among the most basic information collected for
      animals in ecosystems, a human trophic level (HTL) has never been defined. Here,
      we find a global HTL of 2.21, i.e., the trophic level of anchoveta. This value
      has increased with time, consistent with the global trend toward diets higher in
      meat. National HTLs ranging between 2.04 and 2.57 reflect a broad diversity of
      diet, although cluster analysis of countries with similar dietary trends reveals
      only five major groups. We find significant links between socio-economic and
      environmental indicators and global dietary trends. We demonstrate that the HTL
      is a synthetic index to monitor human diets and provides a baseline to compare
      diets between countries. 

PMID- 24297883
TI  - Oxytocin enhances brain function in children with autism.
AB  - Following intranasal administration of oxytocin (OT), we measured, via functional
      MRI, changes in brain activity during judgments of socially (Eyes) and
      nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning
      autism spectrum disorder (ASD). OT increased activity in the striatum, the middle
      frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and
      the left superior temporal sulcus. In the striatum, nucleus accumbens, left
      posterior superior temporal sulcus, and left premotor cortex, OT increased
      activity during social judgments and decreased activity during nonsocial
      judgments. Changes in salivary OT concentrations from baseline to 30 min
      postadministration were positively associated with increased activity in the
      right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT
      may thus selectively have an impact on salience and hedonic evaluations of
      socially meaningful stimuli in children with ASD, and thereby facilitate social
      attunement. These findings further the development of a neurophysiological
      systems-level understanding of mechanisms by which OT may enhance social
      functioning in children with ASD. 

PMID- 24297884
TI  - Male contraception via simultaneous knockout of alpha1A-adrenoceptors and P2X1
      purinoceptors in mice.
AB  - Therapeutic targets for male contraception are associated with numerous problems
      due to their focus on disrupting spermatogenesis or hormonal mechanisms to
      produce dysfunctional sperm. Here we describe the dual genetic deletion of
      alpha1A-adrenergic G protein-coupled receptors (adrenoceptors) and P2X1
      purinoceptor ligand gated ion channels in male mice, thereby blocking
      sympathetically mediated sperm transport through the vas deferens during the
      emission phase of ejaculation. This modification produced 100% infertility
      without effects on sexual behavior or function. Sperm taken from the cauda
      epididymides of double knockout mice were microscopically normal and motile.
      Furthermore, double knockout sperm were capable of producing normal offspring
      following intracytoplasmic sperm injection into wild-type ova and implantation of
      the fertilized eggs into foster mothers. Blood pressure and baroreflex function
      was reduced in double knockout mice, but no more than single knockout of alpha1A
      adrenoceptors alone. These results suggest that this autonomic method of male
      contraception appears free of major physiological and behavioral side effects. In
      addition, they provide conclusive proof of concept that pharmacological
      antagonism of the P2X1-purinoceptor and alpha1A-adrenoceptor provides a safe and
      effective therapeutic target for a nonhormonal, readily reversible male
      contraceptive. 

PMID- 24297885
TI  - Role for regulated phosphatase activity in generating mitotic oscillations in
      Xenopus cell-free extracts.
AB  - Although current textbook explanations of cell-cycle control in eukaryotes
      emphasize the periodic activation of cyclin-dependent protein kinases (CDKs),
      recent experimental observations suggest a significant role for the periodic
      activation and inactivation of a CDK-counteracting protein phosphatase 2A with a
      B55delta subunit (PP2A:B55delta), during mitotic cycles in frog-egg extracts and
      early embryos. In this paper, we extend an earlier mathematical model of
      embryonic cell cycles to include experimentally motivated roles for PP2A:B55delta
      and its regulation by Greatwall kinase. Our model is consistent with what is
      already known about the regulation of CDK and PP2A:B55delta in frog eggs, and it
      suggests a previously undescribed role for the Greatwall-PP2A:B55delta
      interaction in creating a toggle switch for activation of the anaphase-promoting
      complex as embryonic cells exit mitosis and return to interphase. 

PMID- 24297886
TI  - Edge-controlled growth and kinetics of single-crystal graphene domains by
      chemical vapor deposition.
AB  - The controlled growth of large-area, high-quality, single-crystal graphene is
      highly desired for applications in electronics and optoelectronics; however, the
      production of this material remains challenging because the atomistic mechanism
      that governs graphene growth is not well understood. The edges of graphene, which
      are the sites at which carbon accumulates in the two-dimensional honeycomb
      lattice, influence many properties, including the electronic properties and
      chemical reactivity of graphene, and they are expected to significantly influence
      its growth. We demonstrate the growth of single-crystal graphene domains with
      controlled edges that range from zigzag to armchair orientations via growth
      etching-regrowth in a chemical vapor deposition process. We have observed that
      both the growth and the etching rates of a single-crystal graphene domain
      increase linearly with the slanted angle of its edges from 0 degrees  to ~19
      degrees  and that the rates for an armchair edge are faster than those for a
      zigzag edge. Such edge-structure-dependent growth/etching kinetics of graphene
      can be well explained at the atomic level based on the concentrations of the
      kinks on various edges and allow the evolution and control of the edge and
      morphology in single-crystal graphene following the classical kinetic Wulff
      construction theory. Using these findings, we propose several strategies for the
      fabrication of wafer-sized, high-quality, single-crystal graphene. 

PMID- 24297887
TI  - Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme
      environments in mammals of the Tibet plateau.
AB  - Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however,
      relatively little is known about the role that p53 variations may play in
      environmental adaptation. Here we report that codon asparagine-104 (104N) and
      glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor
      (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable,
      meeting the environmental stresses of the Tibetan plateau. They differ from
      serine-104 (104S) seen in other rodents, including the lowland subterranean zokor
      Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed
      mutational analysis in human cell lines, the codon 104N variation in M. baileyi
      is responsible for the adaptive balance of the transactivation of apoptotic genes
      under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus
      oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither
      104N nor 104E affects the cell-cycle genes. We propose that these variations in
      p53 codon 104 are an outcome of environmental adaptation and evolutionary
      selection that enhance cellular strategies for surviving the environmental
      stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in
      M. baileyi) in the stressful environments of the Qinghai-Tibet plateau. 

PMID- 24297888
TI  - Bioluminescent imaging of drug efflux at the blood-brain barrier mediated by the
      transporter ABCG2.
AB  - ATP-binding cassette (ABC) transporters are a group of transmembrane proteins
      that maintain chemical homeostasis through efflux of compounds out of organelles
      and cells. Among other functions, ABC transporters play a key role in protecting
      the brain parenchyma by efflux of xenobiotics from capillary endothelial cells at
      the blood-brain barrier (BBB). They also prevent the entry of therapeutic drugs
      at the BBB, thereby limiting their efficacy. One of the key transporters playing
      this role is ABCG2. Although other ABC transporters can be studied through
      various imaging modalities, no specific probe exists for imaging ABCG2 function
      in vivo. Here we show that D-luciferin, the endogenous substrate of firefly
      luciferase, is a specific substrate for ABCG2. We hypothesized that ABCG2
      function at the BBB could be evaluated by using bioluminescence imaging in
      transgenic mice expressing firefly luciferase in the brain. Bioluminescence
      signal in the brain of mice increased with coadministration of the ABCG2
      inhibitors Ko143, gefitinib, and nilotinib, but not an ABCB1 inhibitor. This
      method for imaging ABCG2 function at the BBB will facilitate understanding of the
      function and pharmacokinetic inhibition of this transporter.

PMID- 24297889
TI  - Coevolutionary signals across protein lineages help capture multiple protein
      conformations.
AB  - A long-standing problem in molecular biology is the determination of a complete
      functional conformational landscape of proteins. This includes not only proteins'
      native structures, but also all their respective functional states, including
      functionally important intermediates. Here, we reveal a signature of functionally
      important states in several protein families, using direct coupling analysis,
      which detects residue pair coevolution of protein sequence composition. This
      signature is exploited in a protein structure-based model to uncover
      conformational diversity, including hidden functional configurations. We
      uncovered, with high resolution (mean ~1.9 A rmsd for nonapo structures),
      different functional structural states for medium to large proteins (200-450 aa)
      belonging to several distinct families. The combination of direct coupling
      analysis and the structure-based model also predicts several intermediates or
      hidden states that are of functional importance. This enhanced sampling is
      broadly applicable and has direct implications in protein structure determination
      and the design of ligands or drugs to trap intermediate states.

PMID- 24297890
TI  - Optical control of an ion channel gate.
AB  - The powerful optogenetic pharmacology method allows the optical control of
      neuronal activity by photoswitchable ligands tethered to channels and receptors.
      However, this approach is technically demanding, as it requires the design of
      pharmacologically active ligands. The development of versatile technologies
      therefore represents a challenging issue. Here, we present optogating, a method
      in which the gating machinery of an ATP-activated P2X channel was reprogrammed to
      respond to light. We found that channels covalently modified by azobenzene
      containing reagents at the transmembrane segments could be reversibly turned on
      and off by light, without the need of ATP, thus revealing an agonist-independent,
      light-induced gating mechanism. We demonstrate photocontrol of neuronal activity
      by a light-gated, ATP-insensitive P2X receptor, providing an original tool devoid
      of endogenous sensitivity to delineate P2X signaling in normal and pathological
      states. These findings open new avenues to specifically activate other ion
      channels independently of their natural stimulus. 

PMID- 24297891
TI  - MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between
      MuSK and Lrp4.
AB  - Myasthenia gravis (MG) is a severely debilitating autoimmune disease that is due
      to a decrease in the efficiency of synaptic transmission at neuromuscular
      synapses. MG is caused by antibodies against postsynaptic proteins, including (i)
      acetylcholine receptors, the neurotransmitter receptor, (ii) muscle-specific
      kinase (MuSK), a receptor tyrosine kinase essential for the formation and
      maintenance of neuromuscular synapses, and (iii) low-density lipoprotein receptor
      related protein 4 (Lrp4), which responds to neural Agrin by binding and
      stimulating MuSK. Passive transfer studies in mice have shown that IgG4
      antibodies from MuSK MG patients cause disease without requiring complement or
      other immune components, suggesting that these MuSK antibodies cause disease by
      directly interfering with MuSK function. Here we show that pathogenic IgG4
      antibodies to MuSK bind to a structural epitope in the first Ig-like domain of
      MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK
      phosphorylation. In contrast, these IgG4 antibodies have no direct effect on MuSK
      dimerization or MuSK internalization. These results provide insight into the
      unique pathogenesis of MuSK MG and provide clues toward development of specific
      treatment options. 

PMID- 24297892
TI  - DELLA proteins regulate arbuscule formation in arbuscular mycorrhizal symbiosis.
AB  - Most flowering plants are able to form endosymbioses with arbuscular mycorrhizal
      fungi. In this mutualistic association, the fungus colonizes the root cortex and
      establishes elaborately branched hyphae, called arbuscules, within the cortical
      cells. Arbuscule development requires the cellular reorganization of both
      symbionts, and the resulting symbiotic interface functions in nutrient exchange.
      A plant symbiosis signaling pathway controls the development of the symbiosis.
      Several components of the pathway have been identified, but transcriptional
      regulators that control downstream pathways for arbuscule formation are still
      unknown. Here we show that DELLA proteins, which are repressors of gibberellic
      acid (GA) signaling and function at the nexus of several signaling pathways, are
      required for arbuscule formation. Arbuscule formation is severely impaired in a
      Medicago truncatula Mtdella1/Mtdella2 double mutant; GA treatment of wild-type
      roots phenocopies the della double mutant, and a dominant DELLA protein (della1
      Delta18) enables arbuscule formation in the presence of GA. Ectopic expression of
      della1-Delta18 suggests that DELLA activity in the vascular tissue and endodermis
      is sufficient to enable arbuscule formation in the inner cortical cells. In
      addition, expression of della1-Delta18 restores arbuscule formation in the
      symbiosis signaling pathway mutant cyclops/ipd3, indicating an intersection
      between DELLA and symbiosis signaling for arbuscule formation. GA signaling also
      influences arbuscule formation in monocots, and a Green Revolution wheat variety
      carrying dominant DELLA alleles shows enhanced colonization but a limited growth
      response to arbuscular mycorrhizal symbiosis. 

PMID- 24297893
TI  - Molecular basis of usher pore gating in Escherichia coli pilus biogenesis.
AB  - Extracellular fibers called chaperone-usher pathway pili are critical virulence
      factors in a wide range of Gram-negative pathogenic bacteria that facilitate
      binding and invasion into host tissues and mediate biofilm formation. Chaperone
      usher pathway ushers, which catalyze pilus assembly, contain five functional
      domains: a 24-stranded transmembrane beta-barrel translocation domain (TD), a
      beta-sandwich plug domain (PLUG), an N-terminal periplasmic domain, and two C
      terminal periplasmic domains (CTD1 and 2). Pore gating occurs by a mechanism
      whereby the PLUG resides stably within the TD pore when the usher is inactive and
      then upon activation is translocated into the periplasmic space, where it
      functions in pilus assembly. Using antibiotic sensitivity and electrophysiology
      experiments, a single salt bridge was shown to function in maintaining the PLUG
      in the TD channel of the P pilus usher PapC, and a loop between the 12th and 13th
      beta strands of the TD (beta12-13 loop) was found to facilitate pore opening.
      Mutation of the beta12-13 loop resulted in a closed PapC pore, which was unable
      to efficiently mediate pilus assembly. Deletion of the PapH terminator/anchor
      resulted in increased OM permeability, suggesting a role for the proper anchoring
      of pili in retaining OM integrity. Further, we introduced cysteine residues in
      the PLUG and N-terminal periplasmic domains that resulted in a FimD usher with a
      greater propensity to exist in an open conformation, resulting in increased OM
      permeability but no loss in type 1 pilus assembly. These studies provide insights
      into the molecular basis of usher pore gating and its roles in pilus biogenesis
      and OM permeability. 

PMID- 24297894
TI  - Protein recognition and selection through conformational and mutually induced
      fit.
AB  - Protein-protein interactions drive most every biological process, but in many
      instances the domains mediating recognition are disordered. How specificity in
      binding is attained in the absence of defined structure contrasts with well
      established experimental and theoretical work describing ligand binding to
      protein. The signaling protein calmodulin presents a unique opportunity to
      investigate mechanisms for target recognition given that it interacts with
      several hundred different targets. By advancing coarse-grained computer
      simulations and experimental techniques, mechanistic insights were gained in
      defining the pathways leading to recognition and in how target selectivity can be
      achieved at the molecular level. A model requiring mutually induced
      conformational changes in both calmodulin and target proteins was necessary and
      broadly informs how proteins can achieve both high affinity and high specificity.

PMID- 24297895
TI  - A maximum entropy framework for nonexponential distributions.
AB  - Probability distributions having power-law tails are observed in a broad range of
      social, economic, and biological systems. We describe here a potentially useful
      common framework. We derive distribution functions for situations in which a
      "joiner particle" k pays some form of price to enter a community of size , where
      costs are subject to economies of scale. Maximizing the Boltzmann-Gibbs-Shannon
      entropy subject to this energy-like constraint predicts a distribution having a
      power-law tail; it reduces to the Boltzmann distribution in the absence of
      economies of scale. We show that the predicted function gives excellent fits to
      13 different distribution functions, ranging from friendship links in social
      networks, to protein-protein interactions, to the severity of terrorist attacks.
      This approach may give useful insights into when to expect power-law
      distributions in the natural and social sciences. 

PMID- 24297896
TI  - Flavin reduction activates Drosophila cryptochrome.
AB  - Entrainment of circadian rhythms in higher organisms relies on light-sensing
      proteins that communicate to cellular oscillators composed of delayed
      transcriptional feedback loops. The principal photoreceptor of the fly circadian
      clock, Drosophila cryptochrome (dCRY), contains a C-terminal tail (CTT) helix
      that binds beside a FAD cofactor and is essential for light signaling. Light
      reduces the dCRY FAD to an anionic semiquinone (ASQ) radical and increases CTT
      proteolytic susceptibility but does not lead to CTT chemical modification.
      Additional changes in proteolytic sensitivity and small-angle X-ray scattering
      define a conformational response of the protein to light that centers at the CTT
      but also involves regions remote from the flavin center. Reduction of the flavin
      is kinetically coupled to CTT rearrangement. Chemical reduction to either the ASQ
      or the fully reduced hydroquinone state produces the same conformational response
      as does light. The oscillator protein Timeless (TIM) contains a sequence similar
      to the CTT; the corresponding peptide binds dCRY in light and protects the flavin
      from oxidation. However, TIM mutants therein still undergo dCRY-mediated
      degradation. Thus, photoreduction to the ASQ releases the dCRY CTT and promotes
      binding to at least one region of TIM. Flavin reduction by either light or
      cellular reductants may be a general mechanism of CRY activation. 

PMID- 24297897
TI  - Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity.
AB  - Adipogenesis, the conversion of precursor cells into adipocytes, is associated
      with obesity and is mediated by glucocorticoids acting via hitherto poorly
      characterized mechanisms. Dexras1 is a small G protein of the Ras family
      discovered on the basis of its marked induction by the synthetic glucocorticoid
      dexamethasone. We show that Dexras1 mediates adipogenesis and diet-induced
      obesity. Adipogenic differentiation of 3T3-L1 cells is abolished with Dexras1
      depletion, whereas overexpression of Dexras1 elicits adipogenesis. Adipogenesis
      is markedly reduced in mouse embryonic fibroblasts from Dexras1-deleted mice,
      whereas adiposity and diet-induced weight gain are diminished in the mutant mice.

PMID- 24297898
TI  - Mutant KRAS is a druggable target for pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge.
      PDA is addicted to the activity of the mutated KRAS oncogene which is considered
      so far an undruggable therapeutic target. We propose an approach to target KRAS
      effectively in patients using RNA interference. To meet this challenge, we have
      developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER)
      shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was
      assessed for its structural, release, and delivery properties in vitro and in
      vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and
      orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS
      downstream signaling pathway. The LODER-encapsulated siRNA was stable and active
      in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a
      significant decrease in KRAS levels, leading to inhibition of proliferation and
      epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of
      human pancreatic tumor cells and prolonged mouse survival. We report a
      reproducible and safe delivery platform based on a miniature biodegradable
      polymeric matrix, for the controlled and prolonged delivery of siRNA. This
      technology provides the following advantages: (i) siRNA is protected from
      degradation; (ii) the siRNA is slowly released locally within the tumor for
      prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect,
      thereby demonstrating that mutated KRAS is indeed a druggable target. 

PMID- 24297899
TI  - Bordetella pertussis adenylate cyclase toxin translocation across a tethered
      lipid bilayer.
AB  - Numerous bacterial toxins can cross biological membranes to reach the cytosol of
      mammalian cells, where they exert their cytotoxic effects. Our model toxin, the
      adenylate cyclase (CyaA) from Bordetella pertussis, is able to invade eukaryotic
      cells by translocating its catalytic domain directly across the plasma membrane
      of target cells. To characterize its original translocation process, we designed
      an in vitro assay based on a biomimetic membrane model in which a tethered lipid
      bilayer (tBLM) is assembled on an amine-gold surface derivatized with calmodulin
      (CaM). The assembled bilayer forms a continuous and protein-impermeable boundary
      completely separating the underlying calmodulin (trans side) from the medium
      above (cis side). The binding of CyaA to the tBLM is monitored by surface plasmon
      resonance (SPR) spectroscopy. CyaA binding to the immobilized CaM, revealed by
      enzymatic activity, serves as a highly sensitive reporter of toxin translocation
      across the bilayer. Translocation of the CyaA catalytic domain was found to be
      strictly dependent on the presence of calcium and also on the application of a
      negative potential, as shown earlier in eukaryotic cells. Thus, CyaA is able to
      deliver its catalytic domain across a biological membrane without the need for
      any eukaryotic components besides CaM. This suggests that the calcium-dependent
      CyaA translocation may be driven in part by the electrical field across the
      membrane. This study's in vitro demonstration of toxin translocation across a
      tBLM provides an opportunity to explore the molecular mechanisms of protein
      translocation across biological membranes in precisely defined experimental
      conditions. 

PMID- 24297900
TI  - The king cobra genome reveals dynamic gene evolution and adaptation in the snake
      venom system.
AB  - Snakes are limbless predators, and many species use venom to help overpower
      relatively large, agile prey. Snake venoms are complex protein mixtures encoded
      by several multilocus gene families that function synergistically to cause
      incapacitation. To examine venom evolution, we sequenced and interrogated the
      genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it,
      together with our unique transcriptome, microRNA, and proteome datasets from this
      species, with data from other vertebrates. In contrast to the platypus, the only
      other venomous vertebrate with a sequenced genome, we find that snake toxin genes
      evolve through several distinct co-option mechanisms and exhibit surprisingly
      variable levels of gene duplication and directional selection that correlate with
      their functional importance in prey capture. The enigmatic accessory venom gland
      shows a very different pattern of toxin gene expression from the main venom gland
      and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic
      functions. In addition, tissue-specific microRNA analyses suggested the co-option
      of core genetic regulatory components of the venom secretory system from a
      pancreatic origin. Although the king cobra is limbless, we recovered coding
      sequences for all Hox genes involved in amniote limb development, with the
      exception of Hoxd12. Our results provide a unique view of the origin and
      evolution of snake venom and reveal multiple genome-level adaptive responses to
      natural selection in this complex biological weapon system. More generally, they
      provide insight into mechanisms of protein evolution under strong selection. 

PMID- 24297901
TI  - Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF
      IA.
AB  - Transcription initiation factor I (TIF-IA) plays an essential role in regulating
      ribosomal RNA (rRNA) synthesis by tethering RNA polymerase I (Pol I) to the rDNA
      promoter. We have found that activated Akt enhances rRNA synthesis through the
      phosphorylation of casein kinase IIalpha (CK2alpha) on a threonine residue near
      its N terminus. CK2 in turn phosphorylates TIF-IA, thereby increasing rDNA
      transcription. Activated Akt also stabilizes TIF-IA, induces its translocation to
      the nucleolus, and enhances its interaction with Pol I. Treatment with AZD8055,
      an inhibitor of both Akt and mammalian target of rapamycin phosphorylation, but
      not with rapamycin, disrupts Akt-mediated TIF-IA stability, translocation, and
      activity. These data support a model in which activated Akt enhances rRNA
      synthesis both by preventing TIF-IA degradation and phosphorylating CK2alpha,
      which in turn phosphorylates TIF-IA. This model provides an explanation for the
      ability of activated Akt to promote cell proliferation and, potentially,
      transformation. 

PMID- 24297902
TI  - The Burmese python genome reveals the molecular basis for extreme adaptation in
      snakes.
AB  - Snakes possess many extreme morphological and physiological adaptations.
      Identification of the molecular basis of these traits can provide novel
      understanding for vertebrate biology and medicine. Here, we study snake biology
      using the genome sequence of the Burmese python (Python molurus bivittatus), a
      model of extreme physiological and metabolic adaptation. We compare the python
      and king cobra genomes along with genomic samples from other snakes and perform
      transcriptome analysis to gain insights into the extreme phenotypes of the
      python. We discovered rapid and massive transcriptional responses in multiple
      organ systems that occur on feeding and coordinate major changes in organ size
      and function. Intriguingly, the homologs of these genes in humans are associated
      with metabolism, development, and pathology. We also found that many snake
      metabolic genes have undergone positive selection, which together with the rapid
      evolution of mitochondrial proteins, provides evidence for extensive adaptive
      redesign of snake metabolic pathways. Additional evidence for molecular
      adaptation and gene family expansions and contractions is associated with major
      physiological and phenotypic adaptations in snakes; genes involved are related to
      cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure,
      including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic
      protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore
      structure, and nucleotide substitution rates indicate major shifts in the
      structure and evolution of snake genomes compared with other amniotes. Phenotypic
      and physiological novelty in snakes seems to be driven by system-wide
      coordination of protein adaptation, gene expression, and changes in the structure
      of the genome. 

PMID- 24297903
TI  - Stoichiometry for activation of neuronal alpha7 nicotinic receptors.
AB  - Neuronal alpha7 nicotinic receptors elicit rapid cation influx in response to
      acetylcholine (ACh) or its hydrolysis product choline. They contribute to
      cognition, synaptic plasticity, and neuroprotection and have been implicated in
      neurodegenerative and neuropsychiatric disorders. alpha7, however, often
      localizes distal to sites of nerve-released ACh and binds ACh with low affinity,
      and thus elicits its biological response with low agonist occupancy. To assess
      the function of alpha7 when ACh occupies fewer than five of its identical binding
      sites, we measured the open-channel lifetime of individual receptors in which
      four of the five ACh binding sites were disabled. To improve the time resolution
      of the inherently brief alpha7 channel openings, background mutations or a
      potentiator was used to increase open duration. We find that, in receptors with
      only one intact binding site, the open-channel lifetime is indistinguishable from
      receptors with five intact binding sites, counter to expectations from
      prototypical neurotransmitter-gated ion channels where the open-channel lifetime
      increases with the number of binding sites occupied by agonist. Replacing the
      membrane-embedded domain of alpha7 by that of the related 5-HT3A receptor
      increases the number of sites that need to be occupied to achieve the maximal
      open-channel lifetime, thus revealing a unique interdependence between the
      detector and actuator domains of these receptors. The distinctive ability of a
      single occupancy to elicit a full biological response adapts alpha7 to volume
      transmission, a prevalent mechanism of ACh-mediated signaling in the nervous
      system and nonneuronal cells. 

PMID- 24297904
TI  - Sex differences in the structural connectome of the human brain.
AB  - Sex differences in human behavior show adaptive complementarity: Males have
      better motor and spatial abilities, whereas females have superior memory and
      social cognition skills. Studies also show sex differences in human brains but do
      not explain this complementarity. In this work, we modeled the structural
      connectome using diffusion tensor imaging in a sample of 949 youths (aged 8-22 y,
      428 males and 521 females) and discovered unique sex differences in brain
      connectivity during the course of development. Connection-wise statistical
      analysis, as well as analysis of regional and global network measures, presented
      a comprehensive description of network characteristics. In all supratentorial
      regions, males had greater within-hemispheric connectivity, as well as enhanced
      modularity and transitivity, whereas between-hemispheric connectivity and cross
      module participation predominated in females. However, this effect was reversed
      in the cerebellar connections. Analysis of these changes developmentally
      demonstrated differences in trajectory between males and females mainly in
      adolescence and in adulthood. Overall, the results suggest that male brains are
      structured to facilitate connectivity between perception and coordinated action,
      whereas female brains are designed to facilitate communication between analytical
      and intuitive processing modes. 

PMID- 24297905
TI  - Regulation of Son of sevenless by the membrane-actin linker protein ezrin.
AB  - Receptor tyrosine kinases participate in several signaling pathways through small
      G proteins such as Ras (rat sarcoma). An important component in the activation of
      these G proteins is Son of sevenless (SOS), which catalyzes the nucleotide
      exchange on Ras. For optimal activity, a second Ras molecule acts as an
      allosteric activator by binding to a second Ras-binding site within SOS. This
      allosteric Ras-binding site is blocked by autoinhibitory domains of SOS. We have
      reported recently that Ras activation also requires the actin-binding proteins
      ezrin, radixin, and moesin. Here we report the mechanism by which ezrin modulates
      SOS activity and thereby Ras activation. Active ezrin enhances Ras/MAPK signaling
      and interacts with both SOS and Ras in vivo and in vitro. Moreover, in vitro
      kinetic assays with recombinant proteins show that ezrin also is important for
      the activity of SOS itself. Ezrin interacts with GDP-Ras and with the Dbl
      homology (DH)/pleckstrin homology (PH) domains of SOS, bringing GDP-Ras to the
      proximity of the allosteric site of SOS. These actions of ezrin are antagonized
      by the neurofibromatosis type 2 tumor-suppressor protein merlin. We propose an
      additional essential step in SOS/Ras control that is relevant for human cancer as
      well as all physiological processes involving Ras. 

PMID- 24297906
TI  - Crystal structures of the carbamoylated and cyanated forms of HypE for [NiFe]
      hydrogenase maturation.
AB  - Hydrogenase pleiotropically acting protein (Hyp)E plays a role in biosynthesis of
      the cyano groups for the NiFe(CN)2CO center of [NiFe] hydrogenases by catalyzing
      the ATP-dependent dehydration of the carbamoylated C-terminal cysteine of HypE to
      thiocyanate. Although structures of HypE proteins have been determined, until now
      there has been no structural evidence to explain how HypE dehydrates
      thiocarboxamide into thiocyanate. Here, we report the crystal structures of the
      carbamoylated and cyanated forms of HypE from Thermococcus kodakarensis in
      complex with nucleotides at 1.53- and 1.64-A resolution, respectively.
      Carbamoylation of the C-terminal cysteine (Cys338) of HypE by chemical
      modification is clearly observed in the present structures. In the presence of
      ATP, the thiocarboxamide of Cys338 is successfully dehydrated into the
      thiocyanate. In the carbamoylated state, the thiocarboxamide nitrogen atom of
      Cys338 is close to a conserved glutamate residue (Glu272), but the spatial
      position of Glu272 is less favorable for proton abstraction. On the other hand,
      the thiocarboxamide oxygen atom of Cys338 interacts with a conserved lysine
      residue (Lys134) through a water molecule. The close contact of Lys134 with an
      arginine residue lowers the pKa of Lys134, suggesting that Lys134 functions as a
      proton acceptor. These observations suggest that the dehydration of
      thiocarboxamide into thiocyanate is catalyzed by a two-step deprotonation
      process, in which Lys134 and Glu272 function as the first and second bases,
      respectively. 

PMID- 24297908
TI  - Formation of highly porous aerosol particles by atmospheric freeze-drying in ice
      clouds.
AB  - The cycling of atmospheric aerosols through clouds can change their chemical and
      physical properties and thus modify how aerosols affect cloud microphysics and,
      subsequently, precipitation and climate. Current knowledge about aerosol
      processing by clouds is rather limited to chemical reactions within water
      droplets in warm low-altitude clouds. However, in cold high-altitude cirrus
      clouds and anvils of high convective clouds in the tropics and midlatitudes,
      humidified aerosols freeze to form ice, which upon exposure to subsaturation
      conditions with respect to ice can sublimate, leaving behind residual modified
      aerosols. This freeze-drying process can occur in various types of clouds. Here
      we simulate an atmospheric freeze-drying cycle of aerosols in laboratory
      experiments using proxies for atmospheric aerosols. We find that aerosols that
      contain organic material that undergo such a process can form highly porous
      aerosol particles with a larger diameter and a lower density than the initial
      homogeneous aerosol. We attribute this morphology change to phase separation upon
      freezing followed by a glass transition of the organic material that can preserve
      a porous structure after ice sublimation. A porous structure may explain the
      previously observed enhancement in ice nucleation efficiency of glassy organic
      particles. We find that highly porous aerosol particles scatter solar light less
      efficiently than nonporous aerosol particles. Using a combination of satellite
      and radiosonde data, we show that highly porous aerosol formation can readily
      occur in highly convective clouds, which are widespread in the tropics and
      midlatitudes. These observations may have implications for subsequent cloud
      formation cycles and aerosol albedo near cloud edges. 

PMID- 24297907
TI  - Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with
      working memory and is improved with estrogen treatment.
AB  - Humans and nonhuman primates are vulnerable to age- and menopause-related decline
      in working memory, a cognitive function reliant on the energy-demanding recurrent
      excitation of neurons within Brodmann's Area 46 of the dorsolateral prefrontal
      cortex (dlPFC). Here, we tested the hypothesis that the number and morphology
      (straight, curved, or donut-shaped) of mitochondria in dlPFC presynaptic boutons
      are altered with aging and menopause in rhesus monkeys (Macaca mulatta) and that
      these metrics correlate with delayed response (DR) accuracy, a well-characterized
      measure of dlPFC-dependent working memory. Although presynaptic bouton density or
      size was not significantly different across groups distinguished by age or menses
      status, DR accuracy correlated positively with the number of total and straight
      mitochondria per dlPFC bouton. In contrast, DR accuracy correlated inversely with
      the frequency of boutons containing donut-shaped mitochondria, which exhibited
      smaller active zone areas and fewer docked synaptic vesicles than those with
      straight or curved mitochondria. We then examined the effects of estrogen
      administration to test whether a treatment known to improve working memory
      influences mitochondrial morphology. Aged ovariectomized monkeys treated with
      vehicle displayed significant working memory impairment and a concomitant 44%
      increase in presynaptic donut-shaped mitochondria, both of which were reversed
      with cyclic estradiol treatment. Together, our data suggest that hormone
      replacement therapy may benefit cognitive aging, in part by promoting
      mitochondrial and synaptic health in the dlPFC. 

PMID- 24297909
TI  - Repeated elevational transitions in hemoglobin function during the evolution of
      Andean hummingbirds.
AB  - Animals that sustain high levels of aerobic activity under hypoxic conditions
      (e.g., birds that fly at high altitude) face the physiological challenge of
      jointly optimizing blood-O2 affinity for O2 loading in the pulmonary circulation
      and O2 unloading in the systemic circulation. At high altitude, this challenge is
      especially acute for small endotherms like hummingbirds that have exceedingly
      high mass-specific metabolic rates. Here we report an experimental analysis of
      hemoglobin (Hb) function in South American hummingbirds that revealed a positive
      correlation between Hb-O2 affinity and native elevation. Protein engineering
      experiments and ancestral-state reconstructions revealed that this correlation is
      attributable to derived increases in Hb-O2 affinity in highland lineages, as well
      as derived reductions in Hb-O2 affinity in lowland lineages. Site-directed
      mutagenesis experiments demonstrated that repeated evolutionary transitions in
      biochemical phenotype are mainly attributable to repeated amino acid replacements
      at two epistatically interacting sites that alter the allosteric regulation of Hb
      O2 affinity. These results demonstrate that repeated changes in biochemical
      phenotype involve parallelism at the molecular level, and that mutations with
      indirect, second-order effects on Hb allostery play key roles in biochemical
      adaptation. 

PMID- 24297910
TI  - Lower and upper stem-single-stranded RNA junctions together determine the Drosha
      cleavage site.
AB  - Microprocessor [Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) complex]
      processing of primary microRNA (pri-miRNA) is the critical first step in miRNA
      biogenesis, but how the Drosha cleavage site is determined has been unclear.
      Previous models proposed that the Drosha-DGCR8 complex measures either ~22 nt
      from the upper stem-single-stranded RNA (ssRNA, terminal loop) junction or ~11 nt
      from the lower stem-ssRNA junction to determine the cleavage site. Here, using
      miRNA-offset RNAs to determine the Drosha cleavage site, we show that the
      Microprocessor measures the distances from both the lower and upper stem-ssRNA
      junctions to determine the cleavage site in human cells, and optimal distances
      from both structures are critical to the precision of Drosha processing. If the
      distances are not optimal, Drosha tends to cleave at multiple sites, which can,
      in turn, generate multiple 5' isomiRs. Thus, our results also reveal a mechanism
      of 5' isomiR generation.

PMID- 24297911
TI  - Collybistin activation by GTP-TC10 enhances postsynaptic gephyrin clustering and
      hippocampal GABAergic neurotransmission.
AB  - In many brain regions, gephyrin and GABAA receptor clustering at developing
      inhibitory synapses depends on the guanine nucleotide exchange factor collybistin
      (Cb). The vast majority of Cb splice variants contain an autoinhibitory src
      homology 3 domain, and several synaptic proteins are known to bind to this SH3
      domain and to thereby activate gephyrin clustering. However, many functional
      GABAergic synapses form independently of the known Cb-activating proteins,
      indicating that additional Cb activators must exist. Here we show that the small
      Rho-like GTPase TC10 stimulates Cb-dependent gephyrin clustering by binding in
      its active, GTP-bound state to the pleckstrin homology domain of Cb.
      Overexpression of a constitutively active TC10 variant in neurons causes an
      increase in the density of synaptic gephyrin clusters and mean miniature
      inhibitory postsynaptic current amplitudes, whereas a dominant negative TC10
      variant has opposite effects. The enhancement of Cb-induced gephyrin clustering
      by GTP-TC10 does not depend on the guanine nucleotide exchange activity of Cb but
      involves an interaction that resembles reported interactions of other small
      GTPases with their effectors. Our data indicate that GTP-TC10 activates the major
      src homology 3 domain-containing Cb variants by relieving autoinhibition and thus
      define an alternative GTPase-driven signaling pathway in the genesis of
      inhibitory synapses. 

PMID- 24297912
TI  - RH5-Basigin interaction plays a major role in the host tropism of Plasmodium
      falciparum.
AB  - Plasmodium falciparum, the cause of almost all human malaria mortality, is a
      member of the Laverania subgenus which infects African great apes. Interestingly,
      Laverania parasites exhibit strict host specificity in their natural environment:
      P. reichenowi, P. billcollinsi, and P. gaboni infect only chimpanzees; P.
      praefalciparum, P. blacklocki, and P. adleri are restricted to gorillas, and P.
      falciparum is pandemic in humans. The molecular mechanism(s) responsible for
      these host restrictions are not understood, although the interaction between the
      parasite blood-stage invasion ligand EBA175 and the host erythrocyte receptor
      Glycophorin-A (GYPA) has been implicated previously. We reexamined the role of
      the EBA175-GYPA interaction in host tropism using recombinant proteins and
      biophysical assays and found that EBA175 orthologs from the chimpanzee-restricted
      parasites P. reichenowi and P. billcollinsi both bound to human GYPA with
      affinities similar to that of P. falciparum, suggesting that the EBA175-GYPA
      interaction is unlikely to be the sole determinant of Laverania host specificity.
      We next investigated the contribution of the recently discovered Reticulocyte
      binding protein Homolog 5 (RH5)-Basigin (BSG) interaction in host-species
      selectivity and found that P. falciparum RH5 bound chimpanzee BSG with a
      significantly lower affinity than human BSG and did not bind gorilla BSG,
      mirroring the known host tropism of P. falciparum. Using site-directed
      mutagenesis, we identified residues in BSG that are responsible for the species
      specificity of PfRH5 binding. Consistent with the essential role of the PfRH5-BSG
      interaction in erythrocyte invasion, we conclude that species-specific
      differences in the BSG receptor provide a molecular explanation for the
      restriction of P. falciparum to its human host. 

PMID- 24297913
TI  - Structural snapshots illustrate the catalytic cycle of beta-galactocerebrosidase,
      the defective enzyme in Krabbe disease.
AB  - Glycosphingolipids are ubiquitous components of mammalian cell membranes, and
      defects in their catabolism by lysosomal enzymes cause a diverse array of
      diseases. Deficiencies in the enzyme beta-galactocerebrosidase (GALC) cause
      Krabbe disease, a devastating genetic disorder characterized by widespread
      demyelination and rapid, fatal neurodegeneration. Here, we present a series of
      high-resolution crystal structures that illustrate key steps in the catalytic
      cycle of GALC. We have captured a snapshot of the short-lived enzyme-substrate
      complex illustrating how wild-type GALC binds a bona fide substrate. We have
      extensively characterized the enzyme kinetics of GALC with this substrate and
      shown that the enzyme is active in crystallo by determining the structure of the
      enzyme-product complex following extended soaking of the crystals with this same
      substrate. We have also determined the structure of a covalent intermediate that,
      together with the enzyme-substrate and enzyme-product complexes, reveals
      conformational changes accompanying the catalytic steps and provides key
      mechanistic insights, laying the foundation for future design of pharmacological
      chaperones. 

PMID- 24297914
TI  - Phosphorylated K-Ras limits cell survival by blocking Bcl-xL sensitization of
      inositol trisphosphate receptors.
AB  - K-Ras4B is targeted to the plasma membrane by a farnesyl modification that
      operates in conjunction with a polybasic domain. We characterized a farnesyl
      electrostatic switch whereby protein kinase C phosphorylates K-Ras4B on serine
      181 in the polybasic region and thereby induces translocation from the plasma
      membrane to internal membranes that include the endoplasmic reticulum (ER) and
      outer mitochondrial membrane. This translocation is associated with cell death.
      Here we have explored the mechanism of phospho-K-Ras4B toxicity and found that
      GTP-bound, phosphorylated K-Ras4B associates with inositol trisphosphate
      receptors on the ER in a Bcl-xL-dependent fashion and, in so doing, blocks the
      ability of Bcl-xL to potentiate the InsP3 regulated flux of calcium from ER to
      mitochondria that is required for efficient respiration, inhibition of autophagy,
      and cell survival. Thus, we have identified inositol trisphosphate receptors as
      unique effectors of K-Ras4B that antagonize the prosurvival signals of other K
      Ras effectors. 

PMID- 24297915
TI  - On the materials basis of modern society.
AB  - It is indisputable that modern life is enabled by the use of materials in its
      technologies. Those technologies do many things very well, largely because each
      material is used for purposes to which it is exquisitely fitted. The result over
      time has been a steady increase in product performance. We show that this
      materials complexity has markedly increased in the past half-century and that
      elemental life cycle analyses characterize rates of recycling and loss. A further
      concern is that of possible scarcity of some of the elements as their use
      increases. Should materials availability constraints occur, the use of substitute
      materials comes to mind. We studied substitution potential by generating a
      comprehensive summary of potential substitutes for 62 different metals in all
      their major uses and of the performance of the substitutes in those applications.
      As we show herein, for a dozen different metals, the potential substitutes for
      their major uses are either inadequate or appear not to exist at all. Further,
      for not 1 of the 62 metals are exemplary substitutes available for all major
      uses. This situation largely decouples materials substitution from price, thereby
      forcing material design changes to be primarily transformative rather than
      incremental. As wealth and population increase worldwide in the next few decades,
      scientists will be increasingly challenged to maintain and improve product
      utility by designing new and better materials, but doing so under potential
      constraints in resource availability. 

PMID- 24297916
TI  - Deconstructing complexin function in activating and clamping Ca2+-triggered
      exocytosis by comparing knockout and knockdown phenotypes.
AB  - Complexin, a presynaptic protein that avidly binds to assembled SNARE complexes,
      is widely acknowledged to activate Ca(2+)-triggered exocytosis. In addition,
      studies of invertebrate complexin mutants and of mouse neurons with a double
      knockdown (DKD) of complexin-1 and -2 suggested that complexin maintains the
      readily releasable pool (RRP) of vesicles and clamps spontaneous exocytosis. In
      contrast, studies of mouse neurons with a double knockout (DKO) of complexin-1
      and -2, largely carried out in hippocampal autapses, did not detect changes in
      the RRP size or in spontaneous exocytosis. To clarify complexin function, we here
      directly compared in two different preparations, cultured cortical and olfactory
      bulb neurons, the phenotypes of complexin DKD and DKO neurons. We find that
      complexin-deficient DKD and DKO neurons invariably exhibit a ~50% decrease in
      vesicle priming. Moreover, the DKD consistently increased spontaneous exocytosis,
      but the DKO did so in cortical but not olfactory bulb neurons. Furthermore, the
      complexin DKD but not the complexin DKO caused a compensatory increase in
      complexin-3 and -4 mRNA levels; overexpression of complexin-3 but not complexin-1
      increased spontaneous exocytosis. Complexin-3 but not complexin-1 contains a C
      terminal lipid anchor attaching it to the plasma membrane; addition of a similar
      lipid anchor to complexin-1 converted complexin-1 from a clamp into an activator
      of spontaneous exocytosis. Viewed together, our data suggest that complexin
      generally functions in priming and Ca(2+) triggering of exocytosis, and
      additionally contributes to the control of spontaneous exocytosis dependent on
      the developmental history of a neuron and on the subcellular localization of the
      complexin.

PMID- 24297917
TI  - Stimulus-induced modulation of transcriptional bursting in a single mammalian
      gene.
AB  - Mammalian genes are often transcribed discontinuously as short bursts of RNA
      synthesis followed by longer silent periods. However, how these "on" and "off"
      transitions, together with the burst sizes, are modulated in single cells to
      increase gene expression upon stimulation is poorly characterized. By combining
      single-cell time-lapse luminescence imaging with stochastic modeling of the time
      traces, we quantified the transcriptional responses of the endogenous connective
      tissue growth factor gene to different physiological stimuli: serum and TGF
      beta1. Both stimuli caused a rapid and acute increase in burst sizes. Whereas TGF
      beta1 showed prolonged transcriptional activation mediated by an increase of
      transcription rate, serum stimulation resulted in a large and temporally tight
      first transcriptional burst, followed by a refractory period in the range of
      hours. Our study thus reveals how different physiological stimuli can trigger
      kinetically distinct transcriptional responses of the same gene. 

PMID- 24297918
TI  - Molecular-scale hydrophobic interactions between hard-sphere reference solutes
      are attractive and endothermic.
AB  - The osmotic second virial coefficients, B2, for atomic-sized hard spheres in
      water are attractive (B2 < 0) and become more attractive with increasing
      temperature (DeltaB2/DeltaT < 0) in the temperature range 300 K <= T <= 360 K.
      Thus, these hydrophobic interactions are attractive and endothermic at moderate
      temperatures. Hydrophobic interactions between atomic-sized hard spheres in water
      are more attractive than predicted by the available statistical mechanical
      theory. These results constitute an initial step toward detailed molecular theory
      of additional intermolecular interaction features, specifically, attractive
      interactions associated with hydrophobic solutes. 

PMID- 24297919
TI  - Crystallographic insights into sodium-channel modulation by the beta4 subunit.
AB  - Voltage-gated sodium (Nav) channels are embedded in a multicomponent membrane
      signaling complex that plays a crucial role in cellular excitability. Although
      the mechanism remains unclear, beta-subunits modify Nav channel function and
      cause debilitating disorders when mutated. While investigating whether beta
      subunits also influence ligand interactions, we found that beta4 dramatically
      alters toxin binding to Nav1.2. To explore these observations further, we solved
      the crystal structure of the extracellular beta4 domain and identified (58)Cys as
      an exposed residue that, when mutated, eliminates the influence of beta4 on toxin
      pharmacology. Moreover, our results suggest the presence of a docking site that
      is maintained by a cysteine bridge buried within the hydrophobic core of beta4.
      Disrupting this bridge by introducing a beta1 mutation implicated in epilepsy
      repositions the (58)Cys-containing loop and disrupts beta4 modulation of Nav1.2.
      Overall, the principles emerging from this work (i) help explain tissue-dependent
      variations in Nav channel pharmacology; (ii) enable the mechanistic
      interpretation of beta-subunit-related disorders; and (iii) provide insights in
      designing molecules capable of correcting aberrant beta-subunit behavior. 

PMID- 24297920
TI  - Retrograde transfer RNA nuclear import provides a new level of tRNA quality
      control in Saccharomyces cerevisiae.
AB  - In eukaryotes, transfer RNAs (tRNAs) are transcribed in the nucleus yet function
      in the cytoplasm; thus, tRNA movement within the cell was believed to be
      unidirectional--from the nucleus to the cytoplasm. It is now known that mature
      tRNAs also move in a retrograde direction from the cytoplasm to the nucleus via
      retrograde tRNA nuclear import, a process that is conserved from yeast to
      vertebrates. The biological significance of this tRNA nuclear import is not
      entirely clear. We hypothesized that retrograde tRNA nuclear import might
      function in proofreading tRNAs to ensure that only proper tRNAs reside in the
      cytoplasm and interact with the translational machinery. Here we identify two
      major types of aberrant tRNAs in yeast: a 5', 3' end-extended, spliced tRNA and
      hypomodified tRNAs. We show that both types of aberrant tRNAs accumulate in
      mutant cells that are defective in tRNA nuclear traffic, suggesting that they are
      normally imported into the nucleus and are repaired or degraded. The retrograde
      pathway functions in parallel with the cytoplasmic rapid tRNA decay pathway
      previously demonstrated to monitor tRNA quality, and cells are not viable if they
      lack both pathways. Our data support the hypothesis that the retrograde process
      provides a newly discovered level of tRNA quality control as a pathway that
      monitors both end processing of pre-tRNAs and the modification state of mature
      tRNAs.

PMID- 24297921
TI  - H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting
      MBD1.
AB  - The H19 gene controls the expression of several genes within the Imprinted Gene
      Network (IGN), involved in growth control of the embryo. However, the underlying
      mechanisms of this control remain elusive. Here, we identified the methyl-CpG
      binding domain protein 1 MBD1 as a physical and functional partner of the H19
      long noncoding RNA (lncRNA). The H19 lncRNA-MBD1 complex is required for the
      control of five genes of the IGN. For three of these genes--Igf2 (insulin-like
      growth factor 2), Slc38a4 (solute carrier family 38 member 4), and Peg1
      (paternally expressed gene 1)--both MBD1 and H3K9me3 binding were detected on
      their differentially methylated regions. The H19 lncRNA-MBD1 complex, through its
      interaction with histone lysine methyltransferases, therefore acts by bringing
      repressive histone marks on the differentially methylated regions of these three
      direct targets of the H19 gene. Our data suggest that, besides the differential
      DNA methylation found on the differentially methylated regions of imprinted
      genes, an additional fine tuning of the expressed allele is achieved by a
      modulation of the H3K9me3 marks, mediated by the association of the H19 lncRNA
      with chromatin-modifying complexes, such as MBD1. This results in a precise
      control of the level of expression of growth factors in the embryo.

PMID- 24297922
TI  - Lnk adaptor suppresses radiation resistance and radiation-induced B-cell
      malignancies by inhibiting IL-11 signaling.
AB  - The Lnk (Sh2b3) adaptor protein dampens the response of hematopoietic stem cells
      and progenitors (HSPCs) to a variety of cytokines by inhibiting JAK2 signaling.
      As a consequence, Lnk(-/-) mice develop hematopoietic hyperplasia, which
      progresses to a phenotype resembling the nonacute phase of myeloproliferative
      neoplasm. In addition, Lnk mutations have been identified in human
      myeloproliferative neoplasms and acute leukemia. We find that Lnk suppresses the
      development of radiation-induced acute B-cell malignancies in mice. Lnk-deficient
      HSPCs recover more effectively from irradiation than their wild-type
      counterparts, and this resistance of Lnk(-/-) HSPCs to radiation underlies the
      subsequent emergence of leukemia. A search for the mechanism responsible for
      radiation resistance identified the cytokine IL-11 as being critical for the
      ability of Lnk(-/-) HSPCs to recover from irradiation and subsequently become
      leukemic. In IL-11 signaling, wild-type Lnk suppresses tyrosine phosphorylation
      of the Src homology region 2 domain-containing phosphatase-2/protein tyrosine
      phosphatase nonreceptor type 11 and its association with the growth factor
      receptor-bound protein 2, as well as activation of the Erk MAP kinase pathway.
      Indeed, Src homology region 2 domain-containing phosphatase-2 has a binding motif
      for the Lnk Src Homology 2 domain that is phosphorylated in response to IL-11
      stimulation. IL-11 therefore drives a pathway that enhances HSPC radioresistance
      and radiation-induced B-cell malignancies, but is normally attenuated by the
      inhibitory adaptor Lnk. 

PMID- 24297924
TI  - CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor
      growth, and metastasis.
AB  - Angiogenesis is fundamental to tumorigenesis and an attractive target for
      therapeutic intervention against cancer. We have recently demonstrated that CD13
      (aminopeptidase N) expressed by nonmalignant host cells of unspecified types
      regulate tumor blood vessel development. Here, we compare CD13 wild-type and null
      bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow
      derived cells promote cancer progression via their effect on angiogenesis.
      Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune
      subpopulation directly regulating tumor blood vessel development. Finally, we
      show that these cells are specifically localized within the tumor
      microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+)
      myeloid cells constitute a population of bone marrow-derived cells that promote
      tumor progression and metastasis and are potential candidates for the development
      of targeted antiangiogenic drugs. 

PMID- 24297923
TI  - Cellular distribution of copper to superoxide dismutase involves scaffolding by
      membranes.
AB  - Efficient delivery of copper ions to specific intracellular targets requires
      copper chaperones that acquire metal cargo through unknown mechanisms. Here we
      demonstrate that the human and yeast copper chaperones (CCS) for superoxide
      dismutase 1 (SOD1), long thought to exclusively reside in the cytosol and
      mitochondrial intermembrane space, can engage negatively charged bilayers through
      a positively charged lipid-binding interface. The significance of this membrane
      binding interface is established through SOD1 activity and genetic
      complementation studies in Saccharomyces cerevisiae, showing that recruitment of
      CCS to the membrane is required for activation of SOD1. Moreover, we show that a
      CCS:SOD1 complex binds to bilayers in vitro and that CCS can interact with human
      high affinity copper transporter 1. Shifting current paradigms, we propose that
      CCS-dependent copper acquisition and distribution largely occur at membrane
      interfaces and that this emerging role of the bilayer may reflect a general
      mechanistic aspect of cellular transition metal ion acquisition. 

PMID- 24297925
TI  - Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to
      herpes simplex virus 1 infection.
AB  - Herpes simplex virus 1 (HSV-1) infection triggers specific metabolic changes in
      its host cell. To explore the interactions between cellular metabolism and HSV-1
      infection, we performed an siRNA screen of cellular metabolic genes, measuring
      their effect on viral replication. The screen identified multiple enzymes
      predicted to influence HSV-1 replication, including argininosuccinate synthetase
      1 (AS1), which consumes aspartate as part of de novo arginine synthesis.
      Knockdown of AS1 robustly enhanced viral genome replication and the production of
      infectious virus. Using high-resolution liquid chromatography-mass spectrometry,
      we found that the metabolic phenotype induced by knockdown of AS1 in human
      fibroblasts mimicked multiple aspects of the metabolic program observed during
      HSV-1 infection, including an increase in multiple nucleotides and their
      precursors. Together with the observation that AS1 protein and mRNA levels
      decrease during wild-type infection, this work suggests that reduced AS1 activity
      is partially responsible for the metabolic program induced by infection. 

PMID- 24297926
TI  - Consumer diversity across kingdoms supports multiple functions in a coastal
      ecosystem.
AB  - The global biodiversity crisis impairs the valuable benefits ecosystems provide
      humans. These nature-generated benefits are defined by a multitude of different
      ecosystem functions that operate simultaneously. Although several studies have
      simulated species loss in communities and tracked the response of single
      functions such as productivity or nutrient cycling, these studies have involved
      relatively similar taxa, and seldom are strikingly different functions examined.
      With the exception of highly managed ecosystems such as agricultural fields,
      rarely are we interested in only one function being performed well. Instead, we
      rely on ecosystems to deliver several different functions at the same time. Here,
      we experimentally investigated the extinction impacts of dominant consumers in a
      salt marsh. These consumers are remarkably phylogenetically diverse, spanning two
      kingdoms (i.e., Animalia and Fungi). Our field studies reveal that a diverse
      consumer assemblage significantly enhances simultaneous functioning of disparate
      ecosystem processes (i.e., productivity, decomposition, and infiltration).
      Extreme functional and phylogenetic differences among consumers underlie this
      relationship. Each marsh consumer affected at least one different ecosystem
      function, and each individual function was affected by no more than two
      consumers. The implications of these findings are profound: If we want ecosystems
      to perform many different functions well, it is not just number of species that
      matter. Rather, the presence of species representing markedly different ecologies
      and biology is also essential to maximizing multiple functions. Moreover, this
      work emphasizes the need to incorporate both microcomponents and macrocomponents
      of food webs to accurately predict biodiversity declines on integrated-ecosystem
      functioning. 

PMID- 24297927
TI  - Optimal control of gene expression for fast proteome adaptation to environmental
      change.
AB  - Bacterial populations growing in a changing world must adjust their proteome
      composition in response to alterations in the environment. Rapid proteome
      responses to growth medium changes are expected to increase the average growth
      rate and fitness value of these populations. Little is known about the dynamics
      of proteome change, e.g., whether bacteria use optimal strategies of gene
      expression for rapid proteome adjustments and if there are lower bounds to the
      time of proteome adaptation in response to growth medium changes. To begin
      answering these types of questions, we modeled growing bacteria as
      stoichiometrically coupled networks of metabolic pathways. These are balanced
      during steady-state growth in a constant environment but are initially unbalanced
      after rapid medium shifts due to a shortage of enzymes required at higher
      concentrations in the new environment. We identified an optimal strategy for
      rapid proteome adjustment in the absence of protein degradation and found a lower
      bound to the time of proteome adaptation after medium shifts. This minimal time
      is determined by the ratio between the Kullback-Leibler distance from the pre- to
      the postshift proteome and the postshift steady-state growth rate. The dynamics
      of optimally controlled proteome adaptation has a simple analytical solution. We
      used detailed numerical modeling to demonstrate that realistic bacterial control
      systems can emulate this optimal strategy for rapid proteome adaptation. Our
      results may provide a conceptual link between the physiology and population
      genetics of growing bacteria. 

PMID- 24297928
TI  - Visible light alters yeast metabolic rhythms by inhibiting respiration.
AB  - Exposure of cells to visible light in nature or in fluorescence microscopy often
      is considered to be relatively innocuous. However, using the yeast respiratory
      oscillation (YRO) as a sensitive measurement of metabolism, we find that non-UV
      visible light has a significant impact on yeast metabolism. Blue/green
      wavelengths of visible light shorten the period and dampen the amplitude of the
      YRO, which is an ultradian rhythm of cell metabolism and transcription. The
      wavelengths of light that have the greatest effect coincide with the peak
      absorption regions of cytochromes. Moreover, treating yeast with the electron
      transport inhibitor sodium azide has similar effects on the YRO as visible light.
      Because impairment of respiration by light would change several state variables
      believed to play vital roles in the YRO (e.g., oxygen tension and ATP levels), we
      tested oxygen's role in YRO stability and found that externally induced oxygen
      depletion can reset the phase of the oscillation, demonstrating that respiratory
      capacity plays a role in the oscillation's period and phase. Light-induced damage
      to the cytochromes also produces reactive oxygen species that up-regulate the
      oxidative stress response gene TRX2 that is involved in pathways that enable
      sustained growth in bright visible light. Therefore, visible light can modulate
      cellular rhythmicity and metabolism through unexpectedly photosensitive pathways.

PMID- 24297929
TI  - GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1
      signaling.
AB  - NMDA-type glutamate receptors (NMDARs) guide the activity-dependent remodeling of
      excitatory synapses and associated dendritic spines during critical periods of
      postnatal brain development. Whereas mature NMDARs composed of GluN1 and GluN2
      subunits mediate synapse plasticity and promote spine growth and stabilization,
      juvenile NMDARs containing GluN3A subunits are thought to inhibit these processes
      via yet unknown mechanisms. Here, we report that GluN3A binds G protein-coupled
      receptor kinase-interacting protein (GIT1), a postsynaptic scaffold that
      assembles actin regulatory complexes, including the Rac1 guanine nucleotide
      exchange factor betaPIX, to promote Rac1 activation in spines. Binding to GluN3A
      limits the synaptic localization of GIT1 and its ability to complex betaPIX,
      leading to decreased Rac1 activation and reduced spine density and size in
      primary cultured neurons. Conversely, knocking out GluN3A favors the formation of
      GIT1/betaPIX complexes and increases the activation of Rac1 and its main effector
      p21-activated kinase. We further show that binding of GluN3A to GIT1 is regulated
      by synaptic activity, a response that might restrict the negative regulatory
      effects of GluN3A on actin signaling to inactive synapses. Our results identify
      inhibition of Rac1/p21-activated kinase actin signaling pathways as an activity
      dependent mechanism mediating the inhibitory effects of GluN3A on spine
      morphogenesis. 

PMID- 24297930
TI  - Two-dimensional Raman-terahertz spectroscopy of water.
AB  - Two-dimensional Raman-terahertz (THz) spectroscopy is presented as a
      multidimensional spectroscopy directly in the far-IR regime. The method is used
      to explore the dynamics of the collective intermolecular modes of liquid water at
      ambient temperatures that emerge from the hydrogen-bond networks water forming.
      Two-dimensional Raman-THz spectroscopy interrogates these modes twice and as such
      can elucidate couplings and inhomogeneities of the various degrees of freedoms.
      An echo in the 2D Raman-THz response is indeed identified, indicating that a
      heterogeneous distribution of hydrogen-bond networks exists, albeit only on a
      very short 100-fs timescale. This timescale appears to be too short to be
      compatible with more extended, persistent structures assumed within a two-state
      model of water. 

PMID- 24297931
TI  - Relaxin-3/RXFP3 system regulates alcohol-seeking.
AB  - Relapse and hazardous drinking represent the most difficult clinical problems in
      treating patients with alcohol use disorders. Using a rat model of alcohol use
      and alcohol-seeking, we demonstrated that central administration of peptide
      antagonists for relaxin family peptide 3 receptor (RXFP3), the cognate receptor
      for the highly conserved neuropeptide, relaxin-3, decreased self-administration
      of alcohol in a dose-related manner and attenuated cue- and stress-induced
      reinstatement following extinction. By comparison, RXFP3 antagonist treatment did
      not significantly attenuate self-administration or reinstatement of sucrose
      seeking, suggesting a selective effect for alcohol. RXFP3 is densely expressed in
      the stress-responsive bed nucleus of the stria terminalis, and bilateral
      injections of RXFP3 antagonist into the bed nucleus of the stria terminalis
      significantly decreased self-administration and stress-induced reinstatement of
      alcohol, suggesting that this brain region may, at least in part, mediate the
      effects of RXFP3 antagonism. RXFP3 antagonist treatment had no effect on general
      ingestive behavior, activity, or procedural memory for lever pressing in the
      paradigms assessed. These data suggest that relaxin-3/RXFP3 signaling regulates
      alcohol intake and relapse-like behavior, adding to current knowledge of the
      brain chemistry of reward-seeking. 

PMID- 24297933
TI  - Suppression of DNA-damage checkpoint signaling by Rsk-mediated phosphorylation of
      Mre11.
AB  - Ataxia telangiectasia mutant (ATM) is an S/T-Q-directed kinase that is critical
      for the cellular response to double-stranded breaks (DSBs) in DNA. Following DNA
      damage, ATM is activated and recruited by the MRN protein complex [meiotic
      recombination 11 (Mre11)/DNA repair protein Rad50/Nijmegen breakage syndrome 1
      proteins] to sites of DNA damage where ATM phosphorylates multiple substrates to
      trigger cell-cycle arrest. In cancer cells, this regulation may be faulty, and
      cell division may proceed even in the presence of damaged DNA. We show here that
      the ribosomal s6 kinase (Rsk), often elevated in cancers, can suppress DSB
      induced ATM activation in both Xenopus egg extracts and human tumor cell lines.
      In analyzing each step in ATM activation, we have found that Rsk targets loading
      of MRN complex components onto DNA at DSB sites. Rsk can phosphorylate the Mre11
      protein directly at S676 both in vitro and in intact cells and thereby can
      inhibit the binding of Mre11 to DNA with DSBs. Accordingly, mutation of S676 to
      Ala can reverse inhibition of the response to DSBs by Rsk. Collectively, these
      data point to Mre11 as an important locus of Rsk-mediated checkpoint inhibition
      acting upstream of ATM activation. 

PMID- 24297934
TI  - Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the
      INO80 chromatin-remodeling complex.
AB  - SNF2 family ATPases are ATP-dependent motors that often function in multisubunit
      complexes to regulate chromatin structure. Although the central role of SNF2
      ATPases in chromatin biology is well established, mechanisms by which their
      catalytic activities are regulated by additional subunits of chromatin-remodeling
      complexes are less well understood. Here we present evidence that the human
      Inositol auxotrophy 80 (Ino80) SNF2 ATPase is subject to regulation at multiple
      levels in the INO80 chromatin-remodeling complex. The zinc finger histidine triad
      domain-containing protein Ies2 (Ino Eighty Subunit 2) functions as a potent
      activator of the intrinsic catalytic activity of the Ino80 ATPase, whereas the YL
      1 family Ies6 (Ino Eighty Subunit 6) and actin-related Arp5 proteins function
      together to promote binding of the Ino80 ATPase to nucleosomes. These findings
      support the idea that both substrate recognition and the intrinsic catalytic
      activities of SNF2 ATPases have evolved as important sites for their regulation. 

PMID- 24297932
TI  - Diversity and abundance of phosphonate biosynthetic genes in nature.
AB  - Phosphonates, molecules containing direct carbon-phosphorus bonds, compose a
      structurally diverse class of natural products with interesting and useful
      biological properties. Although their synthesis in protozoa was discovered more
      than 50 y ago, the extent and diversity of phosphonate production in nature
      remains poorly characterized. The rearrangement of phosphoenolpyruvate (PEP) to
      phosphonopyruvate, catalyzed by the enzyme PEP mutase (PepM), is shared by the
      vast majority of known phosphonate biosynthetic pathways. Thus, the pepM gene can
      be used as a molecular marker to examine the occurrence and abundance of
      phosphonate-producing organisms. Based on the presence of this gene, phosphonate
      biosynthesis is common in microbes, with ~5% of sequenced bacterial genomes and
      7% of genome equivalents in metagenomic datasets carrying pepM homologs.
      Similarly, we detected the pepM gene in ~5% of random actinomycete isolates. The
      pepM-containing gene neighborhoods from 25 of these isolates were cloned,
      sequenced, and compared with those found in sequenced genomes. PEP mutase
      sequence conservation is strongly correlated with conservation of other nearby
      genes, suggesting that the diversity of phosphonate biosynthetic pathways can be
      predicted by examining PEP mutase diversity. We used this approach to estimate
      the range of phosphonate biosynthetic pathways in nature, revealing dozens of
      discrete groups in pepM amplicons from local soils, whereas hundreds were
      observed in metagenomic datasets. Collectively, our analyses show that
      phosphonate biosynthesis is both diverse and relatively common in nature,
      suggesting that the role of phosphonate molecules in the biosphere may be more
      important than is often recognized.

PMID- 24297935
TI  - Ascites analysis by a microfluidic chip allows tumor-cell profiling.
AB  - Ascites tumor cells (ATCs) represent a potentially valuable source of cells for
      monitoring treatment of ovarian cancer as it would obviate the need for more
      invasive surgical biopsies. The ability to perform longitudinal testing of
      ascites in a point-of-care setting could significantly impact clinical trials,
      drug development, and clinical care. Here, we developed a microfluidic chip
      platform to enrich ATCs from highly heterogeneous peritoneal fluid and then
      perform molecular analyses on these cells. We evaluated 85 putative ovarian
      cancer protein markers and found that nearly two-thirds were either nonspecific
      for malignant disease or had low abundance. Using four of the most promising
      markers, we prospectively studied 47 patients (33 ovarian cancer and 14 control).
      We show that a marker set (ATCdx) can sensitively and specifically map ATC
      numbers and, through its reliable enrichment, facilitate additional treatment
      response measurements related to proliferation, protein translation, or pathway
      inhibition. 

PMID- 24297936
TI  - Genome-block expression-assisted association studies discover malaria resistance
      genes in Anopheles gambiae.
AB  - The malaria parasite-resistance island (PRI) of the African mosquito vector,
      Anopheles gambiae, was mapped to five genomic regions containing 80 genes, using
      coexpression patterns of genomic blocks. High-throughput sequencing identified
      347 nonsynonymous single-nucleotide polymorphisms within these genes in
      mosquitoes from malaria-endemic areas in Kenya. Direct association studies
      between nonsynonymous single-nucleotide polymorphisms and Plasmodium falciparum
      infection identified three naturally occurring genetic variations in each of
      three genes (An. gambiae adenosine deaminase, fibrinogen-related protein 30, and
      fibrinogen-related protein 1) that were associated significantly with parasite
      infection. A role for these genes in the resistance phenotype was confirmed by
      RNA interference knockdown assays. Silencing fibrinogen-related protein 30
      increased parasite infection significantly, whereas ablation of fibrinogen
      related protein 1 transcripts resulted in mosquitoes nearly free of parasites.
      The discovered genes and single-nucleotide polymorphisms are anticipated to be
      useful in the development of tools for malaria control in endemic areas in
      Africa. 

PMID- 24297937
TI  - Predicting the X-ray lifetime of protein crystals.
AB  - Radiation damage is a major cause of failure in macromolecular crystallography
      experiments. Although it is always best to evenly illuminate the entire volume of
      a homogeneously diffracting crystal, limitations of the available equipment and
      imperfections in the sample often require a more sophisticated targeting
      strategy, involving microbeams smaller than the crystal, and translations of the
      crystal during data collection. This leads to a highly inhomogeneous distribution
      of absorbed X-rays (i.e., dose). Under these common experimental conditions, the
      relationship between dose and time is nonlinear, making it difficult to design an
      experimental strategy that optimizes the radiation damage lifetime of the
      crystal, or to assign appropriate dose values to an experiment. We present, and
      experimentally validate, a predictive metric diffraction-weighted dose for
      modeling the rate of decay of total diffracted intensity from protein crystals in
      macromolecular crystallography, and hence we can now assign appropriate "dose"
      values to modern experimental setups. Further, by taking the ratio of total
      elastic scattering to diffraction-weighted dose, we show that it is possible to
      directly compare potential data-collection strategies to optimize the diffraction
      for a given level of damage under specific experimental conditions. As an example
      of the applicability of this method, we demonstrate that by offsetting the
      rotation axis from the beam axis by 1.25 times the full-width half maximum of the
      beam, it is possible to significantly extend the dose lifetime of the crystal,
      leading to a higher number of diffracted photons, better statistics, and lower
      overall radiation damage. 

PMID- 24297938
TI  - Revisiting Darwin's conundrum reveals a twist on the relationship between
      phylogenetic distance and invasibility.
AB  - A key goal of invasion biology is to identify the factors that favor species
      invasions. One potential indicator of invasiveness is the phylogenetic distance
      between a nonnative species and species in the recipient community. However,
      predicting invasiveness using phylogenetic information relies on an untested
      assumption: that both biotic resistance and facilitation weaken with increasing
      phylogenetic distance. We test the validity of this key assumption using a
      mathematical model in which a novel species is introduced into communities with
      varying ecological and phylogenetic relationships. Contrary to what is generally
      assumed, we find that biotic resistance and facilitation can either weaken or
      intensify with phylogenetic distance, depending on the mode of interspecific
      interactions (phenotype matching or phenotype differences) and the resulting
      evolutionary trajectory of the recipient community. Thus, we demonstrate that
      considering the mechanisms that drive phenotypic divergence between native and
      nonnative species can provide critical insight into the relationship between
      phylogenetic distance and invasibility. 

PMID- 24297939
TI  - Protein O-mannosylation is crucial for E-cadherin-mediated cell adhesion.
AB  - In recent years protein O-mannosylation has become a focus of attention as a
      pathomechanism underlying severe congenital muscular dystrophies associated with
      neuronal migration defects. A key feature of these disorders is the lack of O
      mannosyl glycans on alpha-dystroglycan, resulting in abnormal basement membrane
      formation. Additional functions of O-mannosylation are still largely unknown.
      Here, we identify the essential cell-cell adhesion glycoprotein epithelial (E)
      cadherin as an O-mannosylated protein and establish a functional link between O
      mannosyl glycans and cadherin-mediated cell-cell adhesion. By genetically and
      pharmacologically blocking protein O-mannosyltransferases, we found that this
      posttranslational modification is essential for preimplantation development of
      the mouse embryo. O-mannosylation-deficient embryos failed to proceed from the
      morula to the blastocyst stage because of defects in the molecular architecture
      of cell-cell contact sites, including the adherens and tight junctions. Using
      mass spectrometry, we demonstrate that O-mannosyl glycans are present on E
      cadherin, the major cell-adhesion molecule of blastomeres, and present evidence
      that this modification is generally conserved in cadherins. Further, the use of
      newly raised antibodies specific for an O-mannosyl-conjugated epitope revealed
      that these glycans are present on early mouse embryos. Finally, our cell
      aggregation assays demonstrated that O-mannosyl glycans are crucial for cadherin
      based cell adhesion. Our results redefine the significance of O-mannosylation in
      humans and other mammals, showing the immense impact of cadherins on normal as
      well as pathogenic cell behavior. 

PMID- 24297941
TI  - Reply to D. Crivellari et al.

PMID- 24297940
TI  - High-dose cytarabine in induction treatment improves the outcome of adult
      patients younger than age 46 years with acute myeloid leukemia: results of the
      EORTC-GIMEMA AML-12 trial.
AB  - PURPOSE: Cytarabine plays a pivotal role in the treatment of patients with acute
      myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily
      dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been
      reached on the benefit of higher dosages of cytarabine. PATIENTS AND METHODS: The
      European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo
      Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a
      randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and
      Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly
      diagnosed patients with AML, age 15 to 60 years, comparing remission induction
      treatment containing daunorubicin, etoposide, and either standard-dose (SD)
      cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose
      (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5,
      and 7). Patients in complete remission (CR) received a single consolidation cycle
      containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12
      hours for 6 days). Subsequently, a stem-cell transplantation was planned. The
      primary end point was survival. RESULTS: At a median follow-up of 6 years,
      overall survival was 38.7% for patients randomly assigned to SD cytarabine and
      42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06;
      multivariable analysis P = .009). For patients younger than age 46 years,
      survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P =
      .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%,
      respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001)
      and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and
      68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all
      ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal
      tandem duplication) mutation, or with secondary AML benefitted from HD
      cytarabine. CONCLUSION: HD cytarabine produces higher remission and survival
      rates than SD cytarabine, especially in patients younger than age 46 years.

PMID- 24297942
TI  - Critical evaluation of disease stabilization as a measure of activity of systemic
      therapy: lessons from trials with arms in which patients do not receive active
      treatment.

PMID- 24297943
TI  - Is taxane-cisplatin-fluorouracil superior to cisplatin-fluorouracil as induction
      chemotherapy in outcome in locally advanced head and neck cancers?

PMID- 24297944
TI  - Influence of conventional cardiovascular risk factors and lifestyle
      characteristics on cardiovascular disease after hematopoietic cell
      transplantation.
AB  - PURPOSE: To determine the influence of modifiable lifestyle factors on the risk
      of cardiovascular disease after hematopoietic cell transplantation (HCT).
      PATIENTS AND METHODS: HCT survivors of >= 1 year treated from 1970 to 2010 (n =
      3,833) were surveyed from 2010 to 2011 on current cardiovascular health and
      related lifestyle factors (smoking, diet, recreational physical activity).
      Responses (n = 2,362) were compared with those from a matched general population
      sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192).
      RESULTS: Compared with NHANES participants, HCT survivors (median age, 55.9
      years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of
      cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%),
      and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of
      hypertension was similar (27.9% v 30.0%), and survivors were less likely to have
      ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension,
      dyslipidemia, and diabetes were independent risk factors for ischemic heart
      disease and cardiomyopathy, and smoking was associated with ischemic heart
      disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk
      factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs >=
      2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with
      greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P <= .01), and lower
      physical activity level was associated with greater risk of hypertension and
      diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among
      HCT survivors attenuated risk of all cardiovascular conditions assessed.
      CONCLUSION: Attention of clinicians to conventional cardiovascular risk factors
      and modifiable lifestyle characteristics offers hope of reducing serious
      cardiovascular morbidity after HCT.

PMID- 24297945
TI  - Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa
      and bevacizumab in metastatic renal cell carcinoma: INTORACT trial.
AB  - PURPOSE: To prospectively determine the efficacy of combination therapy with
      temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in
      metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In a randomized,
      open-label, multicenter, phase III study, patients with previously untreated
      predominantly clear-cell mRCC were randomly assigned, stratified by prior
      nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to
      receive the combination of either temsirolimus (25 mg intravenously, weekly) or
      IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg
      intravenously, every 2 weeks). The primary end point was independently assessed
      progression-free survival (PFS). RESULTS: Median PFS in patients treated with
      temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and
      9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8).
      There were no significant differences in overall survival (25.8 nu 25.5 months;
      HR, 1.0; P = .6) or objective response rate (27.0% nu 27.4%) with
      temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving
      temsirolimus/bevacizumab reported significantly higher overall mean scores in the
      Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 and FKSI
      Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating
      improvement); however, no differences in global health outcome measures were
      observed. Treatment-emergent all-causality grade >= 3 adverse events more common
      (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis,
      hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia
      was more common with IFN/bevacizumab. Incidence of pneumonitis with
      temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2. CONCLUSION:
      Temsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab
      for first-line treatment in clear-cell mRCC.

PMID- 24297946
TI  - Deep molecular response is reached by the majority of patients treated with
      imatinib, predicts survival, and is achieved more quickly by optimized high-dose
      imatinib: results from the randomized CML-study IV.
AB  - PURPOSE: Deep molecular response (MR(4.5)) defines a subgroup of patients with
      chronic myeloid leukemia (CML) who may stay in unmaintained remission after
      treatment discontinuation. It is unclear how many patients achieve MR(4.5) under
      different treatment modalities and whether MR(4.5) predicts survival. PATIENTS
      AND METHODS: Patients from the randomized CML-Study IV were analyzed for
      confirmed MR(4.5) which was defined as >= 4.5 log reduction of BCR-ABL on the
      international scale (IS) and determined by reverse transcriptase polymerase chain
      reaction in two consecutive analyses. Landmark analyses were performed to assess
      the impact of MR(4.5) on survival. RESULTS: Of 1,551 randomly assigned patients,
      1,524 were assessable. After a median observation time of 67.5 months, 5-year
      overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8
      year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70%
      (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly
      with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016).
      Independent of treatment approach, confirmed MR(4.5) at 4 years predicted
      significantly higher survival probabilities than 0.1% to 1% IS, which corresponds
      to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose
      imatinib and early major molecular remission predicted MR(4.5). No patient with
      confirmed MR(4.5) has experienced progression. CONCLUSION: MR(4.5) is a new
      molecular predictor of long-term outcome, is reached by a majority of patients
      treated with imatinib, and is achieved more quickly with optimized high-dose
      imatinib, which may provide an improved therapeutic basis for treatment
      discontinuation in CML.

PMID- 24297947
TI  - Prognosis of women with primary breast cancer diagnosed during pregnancy.

PMID- 24297948
TI  - Reply to D. Crivellari et al.

PMID- 24297949
TI  - TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in
      patients with high-grade prostatic intraepithelial neoplasia.
AB  - PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a
      precursor lesion of prostate cancer (PCa). The predictive value of ERG gene
      fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of
      a randomized clinical trial. PATIENTS AND METHODS: The GTx Protocol G300104
      randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or
      placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As
      part of this phase III clinical trial, a central pathologist evaluated biopsies
      of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow
      up. ERG immunohistochemistry was performed on biopsies from 461 patients and
      evaluated for protein overexpression. RESULTS: ERG expression was detected in
      11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and
      during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed
      with PCa, respectively. Patients with ERG expression were more likely to develop
      PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients
      experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression
      was not associated with age, baseline PSA, Gleason score, or tumor volume.
      CONCLUSION: This study underscores the necessity of more stringent follow-up for
      men with HGPIN that is also positive for ERG overexpression. Clinicians should
      consider molecular characterization of HGPIN as a means to improve risk
      stratification.

PMID- 24297950
TI  - Randomized phase III trial of temsirolimus versus sorafenib as second-line
      therapy after sunitinib in patients with metastatic renal cell carcinoma.
AB  - PURPOSE: This international phase III trial (Investigating Torisel As Second-Line
      Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of
      rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor
      [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with
      metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib.
      PATIENTS AND METHODS: In total, 512 patients were randomly assigned 1:1 to
      receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib
      400 mg twice per day (n = 253), with stratification according to duration of
      prior sunitinib therapy (<= or > 180 days), prognostic risk, histology (clear
      cell or non-clear cell), and nephrectomy status. The primary end point was
      progression-free survival (PFS) by independent review committee assessment.
      Safety, objective response rate (ORR), and overall survival (OS) were secondary
      end points. RESULTS: Primary analysis revealed no significant difference between
      treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07;
      two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were
      4.3 and 3.9 months, respectively. There was a significant OS difference in favor
      of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01).
      Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months,
      respectively. Safety profiles of both agents were consistent with previous
      studies. CONCLUSION: In patients with mRCC and progression on sunitinib, second
      line temsirolimus did not demonstrate a PFS advantage compared with sorafenib.
      The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may
      benefit patients with mRCC.

PMID- 24297952
TI  - Is it better to transfer long-term cancer survivors to general practitioners or
      develop clinics for long-term survivors within the cancer centers?

PMID- 24297951
TI  - Phase III randomized, placebo-controlled, double-blind study of intravenous
      calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity
      (N08CB/Alliance).
AB  - PURPOSE: Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based
      therapy. Intravenous calcium and magnesium have been extensively used to reduce
      oxaliplatin-induced neurotoxicity. This trial was designed to definitively test
      whether calcium/magnesium decreases oxaliplatin-related neurotoxicity. PATIENTS
      AND METHODS: In all, 353 patients with colon cancer undergoing adjuvant therapy
      with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to
      intravenous calcium/magnesium before and after oxaliplatin, a placebo before and
      after, or calcium/magnesium before and placebo after. The primary end point was
      cumulative neurotoxicity measured by the sensory scale of the European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
      Chemotherapy-Induced Peripheral Neuropathy 20 tool. RESULTS: There were no
      statistically significant neuropathy differences among the study arms as measured
      by the primary end point or additional measures of neuropathy, including
      clinician-determined measurement of the time to grade 2 neuropathy by using the
      National Cancer Institute Common Terminology Criteria for Adverse Events scale or
      an oxaliplatin-specific neuropathy scale. In addition, calcium/magnesium did not
      substantially decrease oxaliplatin-induced acute neuropathy. CONCLUSION: This
      study does not support using calcium/magnesium to protect against oxaliplatin
      induced neurotoxicity.

PMID- 24297953
TI  - Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of
      follicular lymphoma: an international phase II study in patients requiring
      treatment according to GELF/BNLI criteria.
AB  - PURPOSE: We report an international, multicenter phase II trial to evaluate the
      efficacy and toxicity of fractionated (90)Y-ibritumomab tiuxetan ((90)Y-IT) as
      initial therapy of follicular lymphoma (FL). PATIENTS AND METHODS: A total of 74
      patients, with a median age of 61 years (range, 28 to 80 years), were recruited
      requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires
      (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78%
      had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL
      International Prognostic Index). Treatment consisted of two doses of (90)Y-IT
      (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20%
      lymphoma infiltration of bone marrow (BM) received one infusion per week for 4
      consecutive weeks of rituximab (375 mg/m(2)) and proceeded to fractionated
      radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of
      lymphoma to less than 20% involvement. The primary end point was end of treatment
      response of the intention-to-treat population. Secondary objectives were safety
      and progression-free survival (PFS). RESULTS: Initial overall response rate (ORR)
      was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3%
      (42 of 72 patients). Nine patients subsequently improved response making an ORR
      of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median
      follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%,
      treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months.
      Thirty patients have experienced disease progression and 24 have required further
      treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4
      infectious episodes or adverse events and manageable hematologic toxicity.
      CONCLUSION: Fractionated RIT using (90)Y-IT is an effective initial treatment for
      advanced-stage FL in patients with higher tumor burden requiring treatment.

PMID- 24297954
TI  - Incidence of new primary melanomas after diagnosis of stage III and IV melanoma.
AB  - PURPOSE: New primary melanomas (NPMs) have developed in some patients with
      metastatic melanoma treated with BRAF inhibitors. We sought to determine the
      background incidence of spontaneous NPMs after a diagnosis of American Joint
      Committee on Cancer/International Union Against Cancer stage III or IV melanoma
      in patients not treated with a BRAF inhibitor. PATIENTS AND METHODS: Patients
      diagnosed with stage III or IV melanoma at Melanoma Institute Australia between
      1983 and 2008 were analyzed, and those who received a BRAF inhibitor were
      excluded. RESULTS: Two hundred twenty-nine (5%) of 4,215 patients with stage III
      melanoma and 43 (1%) of 3,563 patients with stage IV melanoma had at least one
      NPM after diagnosis of stage III or IV disease. The 6-month, 1-year, and 10-year
      cumulative incidence rates of developing an NPM after stage III melanoma were
      1.2% (95% CI, 0.86% to 1.51%), 1.8% (95% CI, 1.44% to 2.26%), and 5.9% (95% CI,
      5.08% to 6.74%), respectively. The 3-month, 6-month, and 1-year cumulative
      incidence rates of NPM after diagnosis of stage IV melanoma were 0.2% (95% CI,
      0.07% to 0.36%), 0.3% (95% CI, 0.15% to 0.51%), and 0.4% (95% CI, 0.25% to 0.7%),
      respectively. In both patients with stage III and stage IV melanoma, male
      patients and patients with a prior history of multiple primaries had a higher
      incidence of NPM. CONCLUSION: Patients with stage III and stage IV melanoma
      remain at risk for development of further primary melanomas, particularly if they
      have a history of multiple primary melanomas before stage III or IV disease. The
      incidence rates are lower than those reported in patients receiving BRAF
      inhibitors. However, the results must be compared with caution because
      dermatologic assessment is more frequent in BRAF inhibitor trials.

PMID- 24297955
TI  - What does a deep molecular response signify?

PMID- 24297956
TI  - Reply to D. Tural et al.

PMID- 24297957
TI  - Reply to U. Tirelli et al.

PMID- 24297958
TI  - IOTN as an assessment of patient eligibility for consultant orthodontic care.

PMID- 24297960
TI  - A comparison of skeletal maturation in patients with tooth agenesis and
      unaffected controls assessed by the cervical vertebral maturation (CVM) index.
AB  - OBJECTIVE: The aims of this study were to (1) investigate if there is a
      difference in skeletal maturation between tooth agenesis and control patients and
      (2) whether skeletal maturation is affected by the severity of tooth agenesis.
      The cervical vertebral maturation (CVM) index can be used to assess skeletal
      maturation. DESIGN: A retrospective cross-sectional study. SETTING: Eastman
      Dental Hospital, London, UK. METHODS AND MATERIALS: A total of 360 cephalograms
      of patients aged 9-17 years (164 males and 196 females) allocated to four
      subgroups (mild, moderate and severe tooth agenesis patients, and controls) were
      assessed retrospectively. There were 90 patients in each of the four subgroups.
      The skeletal maturation of each subject was assessed both quantitatively and
      qualitatively using the CVM index. All patients in the study were either
      currently receiving treatment or had been discharged from the hospital. RESULTS:
      There was no statistically significant relationship between skeletal maturation
      and the presence of tooth agenesis. Furthermore, there was no statistically
      significant relationship between the skeletal maturity of patients and different
      severities of tooth agenesis. CONCLUSIONS: The data obtained from this group of
      patients and using this measurement tool alone does not supply sufficient reason
      to reject the null hypothesis. However, it suggests that it is possible that no
      difference exists between the groups.

PMID- 24297959
TI  - A randomized clinical trial investigating pain associated with superelastic
      nickel-titanium and multistranded stainless steel archwires during the initial
      leveling and aligning phase of orthodontic treatment.
AB  - OBJECTIVE: To investigate and compare the effects of superelastic nickel-titanium
      and multistranded stainless steel archwires on pain during the initial phase of
      orthodontic treatment. DESIGN: A double-blind two-arm parallel design stratified
      randomized clinical trial. SETTING: A single centre in India between December
      2010 and June 2012. A total of 96 participants (48 male and 48 females; 14.1+/
      2.1 years old) were randomized (stratified on age, sex and initial crowding) to
      superelastic nickel-titanium or multistranded stainless steel archwire groups
      using a computer-generated allocation sequence. METHODS: We compared 0.016-inch
      superelastic nickel-titanium and 0.0175-inch multistranded stainless steel wires
      in 0.022-inch slot (Roth prescription) preadjusted edgewise appliances. The
      follow-up period was 14 days. Outcome was assessed with a visual analogue scale
      at baseline and 32 pre-specified follow-up points. Data was analyzed using mixed
      effects model analysis. RESULTS: One participant was lost to follow up and 10
      were excluded from the analysis due to bond failure or incomplete questionnaire
      answers. Ultimately, 85 participants (42 males and 43 females; 14.1+/-2.0 years
      old) were analysed for the final results. No statistically significant difference
      was found for overall pain [F value = 2.65, degrees of freedom (df) = 92.6; P =
      0.1071]. However, compared to multistranded stainless steel wires, pain in
      subjects with superelastic nickel-titanium archwires was significantly greater at
      12 h (t = 2.34; P = 0.0193), as well as at day 1 in the morning (t = 2.21, P =
      0.0273), afternoon (t = 2.11, P = 0.0346) and at bedtime (t = 2.03, P = 0.042).
      CONCLUSION: For overall pain, there was no statistically significant difference
      between the two wires. However, subjects with superelastic nickel-titanium
      archwires had a significantly higher pain at peak level.

PMID- 24297961
TI  - Different manifestations of class II division 2 incisor retroclination and their
      association with dental anomalies.
AB  - OBJECTIVE: To investigate whether there is an association between dental
      developmental anomalies (DDAs) and different manifestations of class II division
      2 (CII/2) malocclusion incisor retroclination. DESIGN: Retrospective comparative
      study. SETTING: Private orthodontic practice in the regions of Lisbon and Porto,
      Portugal. SUBJECTS AND METHODS: The sample comprised 115 CII/2 malocclusions
      distributed into two groups on the basis of incisor retroclination: Group I
      composed of 48 CII/2 with retroclination exclusively of both maxillary central
      incisors; Group II composed of 67 CII/2 with retroclination of all four maxillary
      incisors. Using the initial orthodontic records, it was determined for each
      patient the presence of the following DDAs: tooth impaction, tooth agenesis,
      maxillary lateral incisor microdontia, tooth transpositions and supernumerary
      teeth. RESULTS: Fifty-five per cent of patients were diagnosed with at least one
      of the DDAs studied. In the total sample the prevalence rates were: 20.0% of
      palatal maxillary canine impaction, 27.4% of third molar agenesis, and 15.7% of
      maxillary lateral incisor microdontia. No patient exhibited any transposition or
      supernumerary teeth. The distribution of the DDAs studied by groups revealed a
      strong association of palatal canine impaction, tooth agenesis and maxillary
      lateral incisor microdontia with Group II but not with Group I. CONCLUSION: The
      association of DDAs with CII/2 malocclusion is not common to all types of
      maxillary incisor retroclination, suggesting different etiologic factors among
      the different manifestations of CII/2 incisor retroclination.

PMID- 24297962
TI  - An in vivo study on the incidence and location of fracture in round orthodontic
      archwires.
AB  - OBJECTIVE: The main objective of this in vivo study was to determine the
      incidence and location of fracture in round nickel-titanium (NiTi) and round
      stainless steel orthodontic archwires, both commonly used in orthodontics.
      Secondarily, this study sought to determine if there is any correlation between
      archwire fracture and gender, diameter of the archwire, arch type
      (maxillary/mandibular) or bracket used. DESIGN: In vivo study. MATERIALS AND
      METHODS: One thousand orthodontic patients (1434 archwires) were evaluated during
      regular treatment visits to assess archwire fracture and location. The patient's
      gender, age, type of archwire (round NiTi and round stainless steel), diameter of
      the archwire, arch type, location of fracture (anterior or posterior) and period
      of service before fracture were recorded. STATISTICAL ANALYSIS: Chi-square
      statistical test was utilized to address the frequency and the correlation
      between the different variables. Level of statistical significance (alpha) was
      set at 0.05. RESULTS: Twenty-five archwire failures were reported (1.7%) of the
      total sample size. All fractured archwires were NiTi, and 76% of the fractures
      were located in the posterior region. No statistical significance was found
      between archwire fracture and gender, arch type (maxillary/mandibular), archwire
      diameter or bracket type. CONCLUSION: The frequency of archwire fracture during
      regular orthodontic visits is very low. The most common archwire fracture site is
      the posterior region. NiTi wires are the most commonly fractured archwire. No
      statistically significant correlation exists between archwire fracture and
      gender, arch type, bracket type or diameter of archwire.

PMID- 24297963
TI  - Changes in the lip-line in asymmetrical cases treated with isolated mandibular
      surgery.
AB  - OBJECTIVE: The aim of this study was to investigate changes in the lip-line in
      asymmetrical cases treated with mandibular osteotomy alone. DESIGN: Retrospective
      study. SETTING: Hiroshima University Institute of Biomedical & Health Sciences,
      Hiroshima, Japan METHODS: The subjects in this study consisted of 30 patients
      with an altered lip-line inclination who underwent isolated mandibular osteotomy
      (bilateral or unilateral sagittal split ramus osteotomy or intraoral vertical
      ramus osteotomy) as part of their surgical correction. Frontal cephalograms and
      facial photographs, taken at the first examination and after treatment, were used
      to measure changes in the inclination of the lip-line and cant of the occlusal
      plane, as well as the lateral deviations of hard and soft tissue Menton. RESULTS:
      Inclination of the lip-line after active treatment was significantly improved
      compared with that before treatment. Menton on the hard and soft tissues after
      active treatment also experienced a significant improvement compared with its
      position at first examination. CONCLUSIONS: One-jaw mandibular osteotomy is able
      to improve the inclination of the lip-line even in the presence of an occlusal
      cant. The inclination of the lip-line is corrected in association with sufficient
      lateral movements of Menton on the mandible.

PMID- 24297964
TI  - Retention protocols and use of vacuum-formed retainers among specialist
      orthodontists.
AB  - OBJECTIVE: To evaluate retention protocols and use of vacuum-formed retainers
      (VFRs) among specialist orthodontists. DESIGN: Postal/electronic (e-)
      questionnaire. SETTING: Republic of Ireland. PARTICIPANTS: Members of the Dental
      Council of Ireland Specialist Register of Orthodontists and/or Orthodontic
      Society of Ireland. METHODS: A pilot-tested questionnaire was distributed to 123
      eligible specialist orthodontists. Questions addressed respondent demographics,
      preferred retainer choice in the maxillary and mandibular arches, prescribed wear
      protocols, VFR characteristics and factors influencing retainer choice.
      Statistical analyses were performed using PASW(r) version 18. RESULTS: The
      response rate was 82%. VFRs were the most commonly chosen retainer, prescribed by
      53% of respondents in the maxilla and 33% in the mandible. Full-time followed by
      part-time wear of removable retainers (RRs) was the wear protocol favoured by the
      majority (70-76%). Full occlusal coverage was the VFR design favoured by 93%. VFR
      sheet thicknesses of 1.0 mm (68%) and 0.75 mm (16%) were most commonly
      prescribed. Seventeen per cent were aware that their patients used their VFRs as
      a receptacle for dental bleaching gel. Life-time wear of retainers was advised by
      67-78%. The operator factor that most influenced retainer choice was the pre
      treatment situation (88%). CONCLUSIONS: VFRs were the most common retainer choice
      in the maxilla and mandible with full-time wear followed by part-time wear of RRs
      favoured by most. Full occlusal coverage with a thickness of 1.0 mm was the VFR
      design prescribed by the majority. More than one in six specialist orthodontists
      were aware that their patients used their VFRs as a receptacle for dental
      bleaching gel.

PMID- 24297965
TI  - BOS MOrth cases prize 2011.
AB  - This paper describes the orthodontic treatment of two cases awarded the prize by
      the British Orthodontic Society for best treated cases submitted for the
      Membership in Orthodontics. The first case reports on the treatment of a class
      III malocclusion with increased vertical lower anterior facial proportions and
      dentoalveolar compensation that was treated with orthodontic camouflage. The
      second case reports on the treatment of a class II division II malocclusion with
      reduced vertical lower anterior facial proportions and an overbite complete to
      the palate, which was treated with orthodontic camouflage. 

PMID- 24297966
TI  - Early interceptive treatment in the primary dentition - a case report.
AB  - This article describes treatment of a patient presenting with a class II
      malocclusion, maxillary and mandibular crowding, posterior crossbite and an
      increased deep bite, where the specific treatment goals were achieved in the
      early mixed dentition by only working on the primary teeth. A Haas-type rapid
      maxillary expansion (RME) appliance was modified to be anchored on the primary
      second molars and canines and activated once a day, with each activation equal to
      0.20 mm. The appliance was blocked after 30 days and left as a retainer. After 6
      months, the RME appliance was removed and bands were cemented to the primary
      second molars in order to apply traction with headgear. After complete eruption
      of the mandibular central and lateral incisors, sequential slicing of the lower
      primary teeth was performed to transfer the leeway space from the distal to the
      mesial part of the arch. When the patient had entered the permanent dentition, a
      dental class I relationship was achieved, the crossbite corrected and the
      crowding improved. The overjet and overbite were also improved. No permanent
      teeth were involved during this phase of treatment. The outcome of this case
      report shows that it is possible to work only on primary teeth in the mixed
      dentition and this can be an effective way to correct a class II malocclusion
      with deep bite, posterior crossbite and maxillary and mandibular crowding. 

PMID- 24297970
TI  - The spirit catches you and you fall down.

PMID- 24297971
TI  - Effect of social networks intervention in type 2 diabetes: a partial randomised
      study.
AB  - BACKGROUND: In this partially randomised intervention study, we assessed the
      effect of social networks on the improvement of type 2 diabetes management in a
      largely African-American population in Baltimore. METHODS: Patients in the
      intervention group (n=68) were asked to recruit peers, form small groups, and
      attend monthly diabetes education sessions, emphasising peer support. Patients in
      the control group (n=70) were recruited individually to attend standard diabetes
      education sessions. The primary outcomes were changes in haemoglobin A1C (HbA1c)
      and blood glucose. Secondary outcomes included blood pressure, weight, functional
      status, self-efficacy, perceived cohesion, social network connectedness and
      diabetes knowledge. General linear mixed models were built to assess mean
      absolute changes in primary and secondary outcomes at 3 and 6 months. RESULTS: At
      6 months from baseline, the social network intervention group achieved a larger
      reduction in HbA1c of -0.32% (p<0.0001) and blood glucose of -10.6 mg/dL,
      (p<0.0001) compared to the control group. In analyses of secondary endpoints, the
      intervention group had more favourable outcomes over time for weight, quality of
      life, self-efficacy, social network scores and diabetes knowledge, compared to
      the control group. While blood pressure decreased, and perceived cohesion
      increased in both groups over the duration of the study, the difference between
      groups was not statistically significant. CONCLUSIONS: The social networks
      intervention showed improved integration of patients within their existing
      networks leading to a greater reduction in HbA1c and blood glucose, as well as
      improved behaviour mediating outcomes.

PMID- 24297972
TI  - A community-based multilevel intervention for smoking, physical activity and
      diet: short-term findings from the Community Interventions for Health programme
      in Hangzhou, China.
AB  - BACKGROUND: To assess the short-term impact of a comprehensive, community-based
      multilevel intervention on knowledge, beliefs and practices with respect to
      smoking, physical activity and diet in Hangzhou, China. METHODS: A non
      randomised, controlled, before-after quasi-experimental trial was conducted in
      two intervention areas and one comparison area. The intervention built on a
      socioecological framework and took place across four settings: neighbourhoods,
      schools, workplaces and community health centres. Two independent cross-sectional
      surveys of adults aged 18-64 years at baseline and a subsequent follow-up were
      conducted in 2008/2009 and 2011 in the intervention and comparison areas. A 2
      year intervention programme was begun in mid-2009 and continued until mid-2011.
      RESULTS: A total of 2016 adults at baseline and 2016 adults at follow-up
      completed the survey. Over the 2-year intervention period, the intervention areas
      showed a statistically significant decline (25.2% vs 18.7%, p<0.001) in the
      prevalence of smoking compared with the comparison area (18.0% vs 16.4%,
      p=0.343). The proportion of individuals who had noticed anyone smoking in any of
      nine locations in the previous 30 days demonstrated a statistically significant
      decline in the intervention (78.9% vs 66.5%, p<0.001) and comparison (76.3% vs
      66.5%, p<0.001) areas. The fruit and vegetable consumption score increased in a
      statistically significant manner in the intervention (24.84 vs 25.97, p=0.036)
      and comparison (24.25 vs 26.67, p<0.001) areas. The metabolic equivalent of
      physical activity increased from 1204 to 1386 (p=0.023) in the intervention areas
      compared with 918 to 924 in the comparison area (p=0.201). CONCLUSIONS: After a 2
      year intervention, beneficial changes were noted in the intervention areas with
      respect to smoking and physical activity but not diet. A community-based
      multilevel intervention programme is feasible in urban China.

PMID- 24297973
TI  - Investigating polyuria.

PMID- 24297974
TI  - Importance of clarifying patients' desired role in shared decision making to
      match their level of engagement with their preferences.

PMID- 24297975
TI  - Fall in incidence of HIV in Asia-Pacific region stalls.

PMID- 24297976
TI  - Indebted to international medical graduates.

PMID- 24297977
TI  - Inspections of mental health services will focus more on service users.

PMID- 24297978
TI  - And finally ...

PMID- 24297979
TI  - Non-specialists can reduce symptoms in mental health patients in developing
      countries, says Cochrane review.

PMID- 24297980
TI  - The role of podiatry in the prevention of falls in older people: a JAPMA special
      issue.
AB  - Given the age-related decline in foot strength and flexibility, and the emerging
      evidence that foot problems increase the risk of falls, established guidelines
      for falls prevention recommend that older adults have their feet examined by a
      podiatrist as a precautionary measure. However, these guidelines do not specify
      which intervention activities might be performed. Published in this special issue
      of JAPMA are nine high-quality articles, including seven original studies and two
      basic science reviews, focusing on the benefit and impact of footwear and foot
      and ankle interventions in reducing the risk of falling. The selected studies
      discuss various relevant questions related to podiatric intervention, including
      adherence to intervention; preference and perception of older adults in selecting
      footwear; benefit of insoles, footwear, and nonslip socks in preventing falls;
      fear of falling related to foot problems; benefit of podiatric surgical
      intervention; and benefit of foot and ankle exercise in preventing falls. 

PMID- 24297981
TI  - Older people's perceptions of a multifaceted podiatric medical intervention to
      prevent falls.
AB  - BACKGROUND: Falls are common in older people and are associated with substantial
      health-care costs. A recent randomized controlled trial of a multifaceted
      podiatric medical intervention demonstrated a 36% reduction in the fall rate over
      12 months. We evaluated the acceptability of and levels of satisfaction with this
      intervention in the older people who participated in the trial. METHODS:
      Participants allocated to the intervention group (which included a home-based
      program of foot and ankle exercises, assistance with the purchase of safe
      footwear when necessary, and provision of prefabricated foot orthoses) completed
      a structured questionnaire 6 months after they had received the intervention. The
      questions addressed participants' perceptions of their balance and foot and ankle
      strength, the perceived difficulty of the exercise program, and the degree of
      satisfaction with the footwear and orthoses provided. RESULTS: Of 153
      participants, 134 (87.6%) attended the 6-month follow-up assessment and completed
      the questionnaire. Most participants perceived improvements in balance (62.7%)
      and foot and ankle strength (74.6%) after 6 months of performing the exercises,
      and 86.6% considered the difficulty level of the exercises to be "about right."
      Most participants reported that they were somewhat or very satisfied with the
      footwear (92.3%) and orthoses (81.6%) provided. CONCLUSIONS: The multifaceted
      podiatric medical intervention used in this trial was generally perceived to be
      beneficial and demonstrated high levels of satisfaction among participants.
      Further research is now required to evaluate the feasibility of implementing the
      intervention in a range of clinical practice settings.

PMID- 24297982
TI  - "Good for older ladies, not me": how elderly women choose their shoes.
AB  - BACKGROUND: Footwear selection is important among older adults. Little is known
      about factors that influence footwear selection among older women. If older women
      are to wear better footwear that reduces their risk of falls and foot
      abnormalities, then a better understanding of the factors underlying footwear
      choice is needed. This study aims to identify factors that drive footwear
      selection and use among older community-dwelling women with no history of falls.
      METHODS: A cross-sectional survey using a structured, open-ended questionnaire
      was conducted by telephone interview. The participants were 24 women, 60 to 80
      years old, with no history of falls or requirement for gait aids. The responses
      to open-ended questions were coded and quantified under a qualitative description
      paradigm. RESULTS: The main themes identified about footwear selection were
      aesthetics and comfort. Aesthetics was by far the main factor influencing
      footwear choice. Wearing safe footwear was not identified as a consideration when
      purchasing footwear. CONCLUSIONS: This study indicates that older women are
      driven primarily by aesthetics and comfort in their footwear selection. These
      footwear drivers have implications for health-care providers when delivering fall
      and foot health education.

PMID- 24297983
TI  - Effects of nonslip socks on the gait patterns of older people when walking on a
      slippery surface.
AB  - BACKGROUND: Slips are a common cause of falls, and nonslip socks have been
      marketed to prevent slips in older people. However, few studies have investigated
      the biomechanical and clinical effects of walking in nonslip socks. This study
      aimed to examine gait parameters in older people walking on a slippery surface
      wearing nonslip socks compared with standard sock and barefoot conditions.
      METHODS: Fifteen older people completed five trials of the fast-paced Timed Up
      and Go test while barefoot and while wearing standard socks and nonslip socks.
      Kinematic data (step length, heel horizontal velocity at heel strike, and foot
      floor angle at heel strike) and clinical data (total Timed Up and Go test time,
      total number of steps, number of steps in turn, and observed slips, trips, or
      falls) were collected. RESULTS: Performance on the Timed Up and Go test did not
      differ between the barefoot and nonslip sock conditions; however, participants
      walked more slowly and took shorter steps when wearing standard socks.
      Participants rated nonslip socks to feel less slippery than barefoot and standard
      socks. CONCLUSIONS: Compared with wearing standard socks, wearing nonslip socks
      improves gait performance and may be beneficial in reducing the risk of slipping
      in older people.

PMID- 24297984
TI  - Fear of falling is prevalent in older adults with diabetes mellitus but is
      unrelated to level of neuropathy.
AB  - BACKGROUND: Patients with diabetic peripheral neuropathy (DPN) demonstrate gait
      alterations compared with their nonneuropathic counterparts, which may place them
      at increased risk for falling. However, it is uncertain whether patients with DPN
      also have a greater fear of falling. METHODS: A voluntary group of older adults
      with diabetes was asked to complete a validated fear of falling questionnaire
      (Falls Efficacy Scale International [FES-I]) and instructed to walk 20 m in their
      habitual shoes at their habitual speed. Spatiotemporal parameters of gait (eg,
      stride velocity and gait speed variability) were collected using a validated body
      worn sensor technology. Balance during walking was also assessed using sacral
      motion in the mediolateral and anteroposterior directions. The level of DPN was
      quantified using vibration perception threshold from the great toe. RESULTS:
      Thirty-four diabetic patients (mean +/- SD: age, 67.6 +/- 9.2 years; body mass
      index, 30.9 +/- 5.7; hemoglobin A1c, 7.9% +/- 2.3%) with varying levels of
      neuropathy (mean +/- SD vibration perception threshold, 34.6 +/- 22.9 V) were
      recruited. Most participants (28 of 34, 82%) demonstrated moderate to high
      concern about falling based on their FES-I score. Age (r = 0.6), hemoglobin A1c
      level (r = 0.39), number of steps required to reach steady-state walking (ie,
      gait initiation) (r = 0.4), and duration of double support (r = 0.44) were each
      positively correlated with neuropathy severity (P < .05). Participants with a
      greater fear of falling also walked with slower stride velocities and shorter
      stride lengths (r = -0.3 for both, P < .05). However, no correlation was observed
      between level of DPN and the participant's actual concern about falling.
      CONCLUSIONS: Fear of falling is prevalent in older adults with diabetes mellitus
      but is unrelated to level of neuropathy.

PMID- 24297986
TI  - Balance rehabilitation: promoting the role of virtual reality in patients with
      diabetic peripheral neuropathy.
AB  - BACKGROUND: Individuals with diabetic peripheral neuropathy frequently experience
      concomitant impaired proprioception and postural instability. Conventional
      exercise training has been demonstrated to be effective in improving balance but
      does not incorporate visual feedback targeting joint perception, which is an
      integral mechanism that helps compensate for impaired proprioception in diabetic
      peripheral neuropathy. METHODS: This prospective cohort study recruited 29
      participants (mean +/- SD: age, 57 +/- 10 years; body mass index [calculated as
      weight in kilograms divided by height in meters squared], 26.9 +/- 3.1).
      Participants satisfying the inclusion criteria performed predefined ankle
      exercises through reaching tasks, with visual feedback from the ankle joint
      projected on a screen. Ankle motion in the mediolateral and anteroposterior
      directions was captured using wearable sensors attached to the participant's
      shank. Improvements in postural stability were quantified by measuring center of
      mass sway area and the reciprocal compensatory index before and after training
      using validated body-worn sensor technology. RESULTS: Findings revealed a
      significant reduction in center of mass sway after training (mean, 22%; P = .02).
      A higher postural stability deficit (high body sway) at baseline was associated
      with higher training gains in postural balance (reduction in center of mass sway)
      (r = -0.52, P < .05). In addition, significant improvement was observed in
      postural coordination between the ankle and hip joints (mean, 10.4%; P = .04).
      CONCLUSIONS: The present research implemented a novel balance rehabilitation
      strategy based on virtual reality technology. The method included wearable
      sensors and an interactive user interface for real-time visual feedback based on
      ankle joint motion, similar to a video gaming environment, for compensating
      impaired joint proprioception. These findings support that visual feedback
      generated from the ankle joint coupled with motor learning may be effective in
      improving postural stability in patients with diabetic peripheral neuropathy.

PMID- 24297985
TI  - Hallux valgus surgery may produce early improvements in balance control: results
      of a cross-sectional pilot study.
AB  - BACKGROUND: Hallux valgus (HV) is associated with poorer performance during gait
      and balance tasks and is an independent risk factor for falls in older adults. We
      sought to assess whether corrective HV surgery improves gait and balance.
      METHODS: Using a cross-sectional study design, gait and static balance data were
      obtained from 40 adults: 19 patients with HV only (preoperative group), 10
      patients who recently underwent successful HV surgery (postoperative group), and
      11 control participants. Assessments were made in the clinic using body-worn
      sensors. RESULTS: Patients in the preoperative group generally demonstrated
      poorer static balance control compared with the other two groups. Despite similar
      age and body mass index, postoperative patients exhibited 29% and 63% less center
      of mass sway than preoperative patients during double-and single-support balance
      assessments, respectively (analysis of variance P =.17 and P =.14, respectively
      [both eyes open condition]). Overall, gait performance was similar among the
      groups, except for speed during gait initiation, where lower speeds were
      encountered in the postoperative group compared with the preoperative group
      (Scheffe P = .049). CONCLUSIONS: This study provides supportive evidence
      regarding the benefits of corrective lower-extremity surgery on certain aspects
      of balance control. Patients seem to demonstrate early improvements in static
      balance after corrective HV surgery, whereas gait improvements may require a
      longer recovery time. Further research using a longitudinal study design and a
      larger sample size capable of assessing the long-term effects of HV surgical
      correction on balance and gait is probably warranted.

PMID- 24297987
TI  - Does footwear affect balance?: the views and experiences of people with diabetes
      and neuropathy who have fallen.
AB  - BACKGROUND: Despite falls being a major concern for people living with
      somatosensory deficit, little is known about the perceived impact of footwear and
      footwear features on balance. Clinical relevance is increased given that
      therapeutic footwear is often provided to people with diabetes to reduce foot
      ulcer risk. This qualitative study aims to explore the experiences and views of
      people with diabetes and neuropathy who have recently fallen to understand
      whether footwear type is perceived to affect balance or contribute to falling.
      METHODS: Sixteen individuals (13 men and three women aged 44-83 years) were
      purposively sampled from a larger population of potential participants. Audio
      recorded, in-depth, semistructured interviews were conducted in participant homes
      or at a place preferable to them. Once transcribed verbatim, the data were
      themed, charted, and interpreted using a framework approach. RESULTS: Although
      most participants did not believe that the footwear in which they fell
      contributed to their fall, most revealed how footwear choice influenced their
      balance confidence to undertake daily tasks. Most found their therapeutic
      footwear "difficult" to walk in, "heavy, or "slippery bottomed." Design
      recommendations for enhanced balance included a close fit with tight fastening,
      lightweight, substantial tread, and a firm, molded sole/insole. Complying with
      these recommendations, the hiking sandal was believed to be the most stable and
      safe shoe and was frequently worn as a walking aid to reduce fear of falling and
      boost confidence. CONCLUSIONS: People with diabetic neuropathy have disease
      specific needs and concerns relating to how footwear affects balance. Engaging
      with patients to address those needs and concerns is likely to improve the
      feasibility and acceptability of therapeutic footwear to reduce foot ulcer risk
      and boost balance confidence.

PMID- 24297988
TI  - Footwear interventions: a review of their sensorimotor and mechanical effects on
      balance performance and gait in older adults.
AB  - Footwear interventions, including shoe insoles and foot orthoses, have the
      capacity to enhance balance control and gait in older people. This review
      assessed the evidence for the effect of footwear interventions on static and
      dynamic balance performance and gait in older populations and explored proposed
      theories for underlying sensorimotor and mechanical mechanisms. We searched the
      Medline, EMBASE, CINAHL (the Cumulative Index to Nursing and Allied Health
      Literature), and AMED databases and conducted hand searches. Of 115 relevant
      articles screened, 14 met the predefined inclusion criteria. Articles were
      grouped into one of three categories based on balance task (static balance
      performance during quiet standing, dynamic balance performance during walking,
      and dynamic balance performance during perturbed standing or functional tasks)
      and were scored for methodological quality using the Downs and Black Quality
      Index tool. Footwear interventions seem to alter underlying strategies
      controlling static and dynamic movement patterns through a combination of
      sensorimotor and mechanical mechanisms in older people, including those with
      chronic sensory and musculoskeletal conditions. Evidence shows a consistent trend
      toward footwear interventions markedly improving lateral stability measures,
      which are predictors of falls in the elderly. In-depth investigation of
      neurophysiologic responses to footwear interventions is necessary to help confirm
      any sensorimotor adaptations. The long-term effects of footwear interventions on
      balance, gait, and the prevention of falls in older people require further
      investigation. 

PMID- 24297989
TI  - Effectiveness of foot and ankle exercise programs on reducing the risk of falling
      in older adults: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Foot and ankle (FA) exercise programs might reduce the risk of
      falling in older adults. We sought to systematically review the current
      literature on FA exercise programs targeted at reducing the risk of falling in
      older adults. METHODS: A systematic literature search was performed in the PubMed
      database, the Physiotherapy Evidence Database, the Cumulative Index to Nursing
      and Allied Health Literature, and the Cochrane Central Register of Controlled
      Trials. Articles were included based on the following criteria: 1) randomized
      controlled trial, 2) FA exercise program, and 3) use of fall risk-related motor
      outcomes (strength, balance, flexibility, and functional ability) or use of falls
      as an outcome. Weighted effect sizes (d) were calculated across studies for
      estimating the overall effect of FA exercises on the most frequently reported
      motor outcome parameters. RESULTS: Eight publications met the inclusion criteria.
      Small to moderate overall effects were found for balance (d = 0.46, P < .001) and
      ankle flexibility (d = 0.29, P = .006). No significant overall effects were found
      for ankle plantarflexor strength (d = 0.11, P = .223) and walking performance (d
      = -0.05, P = .404). Controversial results were reported for other functional
      measures. Effects varied depending on the type of intervention. Only one study
      reported improved ankle evertor strength and a significant reduction in falls.
      CONCLUSIONS: Evidence suggests that FA exercise can improve certain fall risk
      related motor outcomes and reduce falls. Limited effects on strength and
      functional ability might be related to insufficient training intensity and lack
      of adherence. Further studies that include progressive strength and flexibility
      training are necessary to validate which FA exercise programs are most effective
      at preventing falls.

PMID- 24297994
TI  - Gata2 cis-element is required for hematopoietic stem cell generation in the
      mammalian embryo.
AB  - The generation of hematopoietic stem cells (HSCs) from hemogenic endothelium
      within the aorta, gonad, mesonephros (AGM) region of the mammalian embryo is
      crucial for development of the adult hematopoietic system. We described a
      deletion of a Gata2 cis-element (+9.5) that depletes fetal liver HSCs, is lethal
      at E13-14 of embryogenesis, and is mutated in an immunodeficiency that progresses
      to myelodysplasia/leukemia. Here, we demonstrate that the +9.5 element enhances
      Gata2 expression and is required to generate long-term repopulating HSCs in the
      AGM. Deletion of the +9.5 element abrogated the capacity of hemogenic endothelium
      to generate HSC-containing clusters in the aorta. Genomic analyses indicated that
      the +9.5 element regulated a rich ensemble of genes that control hemogenic
      endothelium and HSCs, as well as genes not implicated in hematopoiesis. These
      results reveal a mechanism that controls stem cell emergence from hemogenic
      endothelium to establish the adult hematopoietic system. 

PMID- 24297997
TI  - What insurance exchanges mean for physicians.

PMID- 24297996
TI  - Gata2 is required for HSC generation and survival.
AB  - Knowledge of the key transcription factors that drive hematopoietic stem cell
      (HSC) generation is of particular importance for current hematopoietic
      regenerative approaches and reprogramming strategies. Whereas GATA2 has long been
      implicated as a hematopoietic transcription factor and its dysregulated
      expression is associated with human immunodeficiency syndromes and vascular
      integrity, it is as yet unknown how GATA2 functions in the generation of HSCs.
      HSCs are generated from endothelial cells of the major embryonic vasculature
      (aorta, vitelline, and umbilical arteries) and are found in intra-aortic
      hematopoietic clusters. In this study, we find that GATA2 function is essential
      for the generation of HSCs during the stage of endothelial-to-hematopoietic cell
      transition. Specific deletion of Gata2 in Vec (Vascular Endothelial Cadherin)
      expressing endothelial cells results in a deficiency of long-term repopulating
      HSCs and intra-aortic cluster cells. By specific deletion of Gata2 in Vav
      expressing hematopoietic cells (after HSC generation), we further show that GATA2
      is essential for HSC survival. This is in contrast to the known activity of the
      RUNX1 transcription factor, which functions only in the generation of HSCs, and
      highlights the unique requirement for GATA2 function in HSCs throughout all
      developmental stages. 

PMID- 24297995
TI  - Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7
      signals.
AB  - Pre-B cell receptor (pre-BCR) signaling and migration from IL-7-rich environments
      cooperate to drive pre-B cell differentiation via transcriptional programs that
      remain unclear. We show that the Ikaros transcription factor is required for the
      differentiation of large pre-B to small pre-B cells. Mice deleted for Ikaros in
      pro/pre-B cells show a complete block of differentiation at the fraction C'
      stage, and Ikaros-null pre-B cells cannot differentiate upon withdrawal of IL-7
      in vitro. Restoration of Ikaros function rescues pre-B cell differentiation in
      vitro and in vivo and depends on DNA binding. Ikaros is required for the down
      regulation of the pre-BCR, Igkappa germline transcription, and Ig L chain
      recombination. Furthermore, Ikaros antagonizes the IL-7-dependent regulation of
      >3,000 genes, many of which are up- or down-regulated between fractions C' and D.
      Affected genes include those important for survival, metabolism, B cell
      signaling, and function, as well as transcriptional regulators like Ebf1, Pax5,
      and the Foxo1 family. Our data thus identify Ikaros as a central regulator of IL
      7 signaling and pre-B cell development. 

PMID- 24297998
TI  - After the typhoon: how volunteer doctors are bringing medical care to those most
      in need.

PMID- 24297999
TI  - Optimization of configuration parameters in a newly developed digital breast
      tomosynthesis system.
AB  - The purpose of the present work was to investigate the effects of variable
      projection-view (PV) and angular dose (AD) distributions on the reconstructed
      image quality for improving microcalcification detection. The PV densities at
      central and peripheral sites were varied through the distribution of 21 PVs
      acquired over +/- 25 degrees  angular range. To vary the AD distribution, 7 PVs
      in the central region were targeted with two, four and six times the peripheral
      dose, and the number of central PVs receiving four times the peripheral dose was
      increased from 3 to 11. The contrast-to-noise ratio (CNR) for in-focus plane
      quality and the full width at half maximum (FWHM) of artifact spread function
      (ASF) for resolution in the z-direction were used. Although the ASF improved with
      increasing PV densities at two peripheral sites, the CNRs were inferior to those
      obtained with other subsets. With increasing PV density in the central area, the
      vertical resolution decreased but the CNR increased. Although increasing the
      central PV or AD concentrations improved image quality, excessive central
      densities reduced image quality by increasing noise in peripheral views.

PMID- 24298000
TI  - The cell-cycle interactome: a source of growth regulators?
AB  - When plants develop, cell proliferation and cell expansion are tightly controlled
      in order to generate organs with a determinate final size such as leaves. Several
      studies have demonstrated the importance of the cell proliferation phase for leaf
      growth, illustrating that cell-cycle regulation is crucial for correct leaf
      development. A large and complex set of interacting proteins that constitute the
      cell-cycle interactome controls the transition from one cell-cycle phase to
      another. Here, we review the current knowledge on cell-cycle regulators from this
      interactome affecting final leaf size when their expression is altered, mainly in
      Arabidopsis. In addition to the description of mutants of CYCLIN-DEPENDENT
      KINASES (CDKs), CYCLINS (CYCs), and their transcriptional and post-translational
      regulators, a phenotypic analysis of gain- and loss-of-function mutants for 27
      genes encoding proteins that interact with cell-cycle proteins is presented. This
      compilation of information shows that when cell-cycle-related genes are mis
      expressed, leaf growth is often altered and that, seemingly, three main trends
      appear to be crucial in the regulation of final organ size by cell-cycle-related
      genes: (i) cellular compensation; (ii) gene dosage; and (iii) correct transition
      through the G2/M phase by ANAPHASE PROMOTING COMPLEX/CYCLOSOME (APC/C)
      activation. In conclusion, this meta-analysis shows that the cell-cycle
      interactome is enriched in leaf growth regulators, and illustrates the potential
      to identify new leaf growth regulators among putative new cell-cycle regulators.

PMID- 24298001
TI  - Why did it take 19 months to retrieve clinical trial data from a non-profit
      organisation?

PMID- 24298002
TI  - The challenge of reducing neonatal mortality in low- and middle-income countries.

PMID- 24298003
TI  - Environmental risk factors by gender associated with attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Early environmental risk factors associated with attention
      deficit/hyperactivity disorder (ADHD) have been increasingly suggested. Our study
      investigates the maternal, pregnancy, and newborn risk factors by gender for
      children prescribed stimulant medication for treatment of ADHD in Western
      Australia. METHODS: This is a population-based, record linkage case-control
      study. The records of all non-Aboriginal children and adolescents born in Western
      Australia and aged <25 years who were diagnosed with ADHD and prescribed
      stimulant medication (cases = 12,991) were linked to the Midwives Notification
      System (MNS) to obtain maternal, pregnancy, and birth information. The control
      population of 30,071 children was randomly selected from the MNS. RESULTS:
      Mothers of children with ADHD were significantly more likely to be younger, be
      single, have smoked in pregnancy, have labor induced, and experience threatened
      preterm labor, preeclampsia, urinary tract infection in pregnancy, or early term
      delivery irrespective of the gender of the child, compared with the control
      group. In the fully adjusted model, a novel finding was of a possible protective
      effect of oxytocin augmentation in girls. Low birth weight, postterm pregnancy,
      small for gestational age infant, fetal distress, and low Apgar scores were not
      identified as risk factors. CONCLUSIONS: Smoking in pregnancy, maternal urinary
      tract infection, being induced, and experiencing threatened preterm labor
      increase the risk of ADHD, with little gender difference, although oxytocin
      augmentation of labor appears protective for girls. Early term deliveries
      marginally increased the risk of ADHD. Studies designed to disentangle possible
      mechanisms, confounders, or moderators of these risk factors are warranted.

PMID- 24298004
TI  - School violence, mental health, and educational performance in Uganda.
AB  - BACKGROUND: Violence against children from school staff is anecdotally common in
      low- and middle-income countries, but data on prevalence and associations with
      mental health and educational outcomes are lacking. METHODS: We report data from
      a cross-sectional survey conducted in June and July 2012 in Luwero District,
      Uganda. Forty-two primary schools representing 80% of students in the district
      were randomly selected; 100% agreed to participate. The International Society for
      the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child
      Institutional; Strengths and Difficulties Questionnaire; and reading, spelling,
      and math tests were administered. We present descriptive statistics and logistic
      regression models, accounting for the complex sampling scheme used in the survey.
      RESULTS: We surveyed 3706 students and 577 school staff members; 93.3% (SE 1.0%)
      of boys and 94.2% (SE 1.6%) of girls attending primary school reported lifetime
      experience of physical violence from a school staff member, and >50% reported
      experience in the past week. Past-week physical violence was associated with
      increased odds of poor mental health and, for girls, double the odds of poor
      educational performance (adjusted odds ratio = 1.78, 95% confidence interval =
      1.19-2.66). For boys, significant interactions were present. CONCLUSIONS: Despite
      a ban on corporal punishment in Ugandan schools since 1997, the use of violence
      against students is widespread and associated with poor mental health and
      educational performance. School violence may be an important but overlooked
      contributor to disease burden and poor educational performance in low- and middle
      income settings.

PMID- 24298005
TI  - Screening for behavioral health issues in children enrolled in Massachusetts
      Medicaid.
AB  - OBJECTIVES: To understand mandated behavioral health (BH) screening in
      Massachusetts Medicaid including characteristics of screened children, predictors
      of positive screens, and whether screening identifies children without a previous
      BH history. METHODS: Massachusetts mandated BH screening in particularly among
      underidentified groups. 2008. Providers used a billing code and modifier to
      indicate a completed screen and whether a BH need was identified. Using
      MassHealth claims data, children with >= 300 days of eligibility in fiscal year
      (FY) 2009 were identified and categorized into groups based on first use of the
      modifier, screening code, or claim. Bivariate analyses were conducted to
      determine differences among groups. BH history was examined by limiting the
      sample to those continuously enrolled in FY 2008 and 2009. Multivariate logistic
      regression was used to determine predictors of positive screens. RESULTS: Of
      355,490 eligible children, 46% had evidence of screening. Of those with
      modifiers, 12% were positive. Among continuously enrolled children (FY 2008 and
      FY 2009) with evidence of screening, 43% with positive modifiers had no BH
      history. This "newly identified" group were more likely to be female, younger,
      minority, and from rural residences (P < .0001). Among children with modifiers;
      gender (male), age (5-7), being in foster care, recent BH history, and Hispanic
      ethnicity predicted having a positive modifier. CONCLUSIONS: The high rate of
      newly identified Medicaid children with a BH need suggests that screening is
      performing well, particularly among underidentified groups. To better assess
      screening value, future work on cost-effectiveness and the impact on subsequent
      mental health treatment is needed.

PMID- 24298006
TI  - Bronchiolitis management before and after the AAP guidelines.
AB  - BACKGROUND AND OBJECTIVES: Evidence-based practice guidelines for bronchiolitis
      management published by the American Academy of Pediatrics in 2006 recommend
      supportive care with limited diagnostic testing and treatment. We sought to
      determine the impact of these guidelines on the treatment of hospitalized
      children. METHODS: We analyzed data on inpatients with bronchiolitis aged 1 to 24
      months from the Pediatric Health Information System, an administrative billing
      database, from November 1, 2004 to March 31, 2012. We compared trends in use of
      diagnostic and treatment resources before and after the publication of the
      guidelines by using segmented time series. RESULTS: A total of 41 pediatric
      hospitals contributed data to yield 130,262 patients; 58% were male, and 59% were
      publicly insured. Median age was 4.0 months (interquartile range, 2-9).
      Unadjusted analysis showed improvement in utilization rates before and after
      guidelines for diagnostic tests and for medications; however, there was no
      decreased use of antibiotics. A segmented regression analysis also demonstrated
      differences in rates of change before and after guidelines, with significant
      improvement for chest radiography, steroids, and bronchodilators (P < .0001).
      CONCLUSIONS: In a nationally representative cohort of pediatric hospitals,
      publication of the 2006 American Academy of Pediatrics bronchiolitis guidelines
      was associated with significant reductions in the use of diagnostic and
      therapeutic resources.

PMID- 24298007
TI  - Abdominal and lower back pain in pediatric idiopathic stabbing headache.
AB  - Idiopathic stabbing headache (ISH) is a primary headache syndrome characterized
      by transient, sharp, stabbing pains located in the first division of the
      trigeminal nerve. Reports of pediatric ISH are rare, and extracephalic pain in
      pediatric ISH is extremely rare. Here we report the case of a 7-year-old male
      patient suffering from frequent, short, stabbing headache, which was occasionally
      associated with abdominal and lower back pain. Various investigations were
      normal. He was diagnosed with ISH, and valproic acid was administered to relieve
      his headache and accompanying symptoms. Our case demonstrates that abdominal and
      lower back pain may occur in pediatric ISH. This case may provide new evidence
      linking ISH and migraine by showing that extracephalic symptoms accompanying ISH
      are similar to those of migraine. We hypothesize that the mechanism underlying
      the headache and abdominal and lower back pain associated with ISH may be similar
      to that of a migraine headache. Accumulating additional cases by asking specific
      questions regarding the presence of the unusual symptoms presented in our case
      may help to establish a detailed clinical profile of these unfamiliar and
      peculiar symptoms in the pediatric ISH population. 

PMID- 24298008
TI  - Identifying potential kidney donors among newborns undergoing circulatory
      determination of death.
AB  - BACKGROUND: Over 96,000 patients await kidney transplantation in the United
      States, and 35,000 more are wait-listed annually. The demand for donor kidneys
      far outweighs supply, resulting in significant waiting list morbidity and
      mortality. We sought to identify potential kidney donors among newborns because
      en bloc kidney transplantation donation after circulatory determination of death
      (DCDD) may broaden the donor pool. METHODS: We reviewed discharges from our 84
      bed NICU between November 2002 and October 2012 and identified all deaths. The
      mode of death among potential organ donors (weight >= 1.8 kg) was recorded.
      Patients undergoing withdrawal of life support were further evaluated for DCDD
      potential. After excluding patients with medical contraindications, those with
      warm ischemic time (WIT) less than 120 minutes were characterized as potential
      kidney donors. RESULTS: There were 11,201 discharges. Of 609 deaths, 359 patients
      weighed >= 1.8 kg and 159 died after planned withdrawal of life support. The
      exact time of withdrawal could not be determined for 2 patients, and 100 had at
      least 1 exclusion criterion. Of the remaining patients, 42 to 57 infants were
      potential en bloc kidney donors depending on acceptance threshold for WIT.
      Applying a 40% to 70% consent rate range would yield 1.7 to 4 newborn DCDD donors
      per year. CONCLUSIONS: A neonatal DCDD kidney program at our institution could
      provide 2 to 4 paired kidneys for en bloc transplantation each year. Implementing
      a DCDD kidney donation program in NICUs could add a new source of donors and
      increase the number of kidneys available for transplantation.

PMID- 24298009
TI  - Vitamin D intoxication due to an erroneously manufactured dietary supplement in
      seven children.
AB  - Pediatric cases of vitamin D intoxication (VDI) with dietary supplements have not
      been previously reported. We report on 7 children with VDI caused by consumption
      of a fish oil supplement containing an excessively high dose of vitamin D due to
      a manufacturing error. Seven children aged between 0.7 and 4.2 years were
      admitted with symptoms of hypercalcemia. Initial median (range) serum
      concentrations of calcium and 25-hydroxyvitamin D were 16.5 (13.4-18.8) mg/dL and
      620 (340-962) ng/mL, respectively. Repeated questioning of the parents revealed
      use of a fish oil that was produced recently by a local manufacturer. Analysis of
      the fish oil by gas chromatography/mass spectrometry revealed that the vitamin D3
      content was ~4000 times the labeled concentration. Estimated daily amounts of
      vitamin D3 intake varied between 266,000 and 800,000 IU. Patients were
      successfully treated with intravenous hydration, furosemide, and pamidronate
      infusions. With treatment, serum calcium returned to the normal range within 3
      days (range: 2-7 days). Serum 25-hydroxyvitamin D levels normalized within 2 to 3
      months. Complications, including nephrocalcinosis, were not observed throughout
      the 1-year follow-up. In conclusion, errors in manufacturing of dietary
      supplements may be a cause of VDI in children. Physicians should be aware of this
      possibility in unexplained VDI cases and repeatedly question the families about
      dietary supplement use. To prevent the occurrence of such unintentional
      incidents, manufacturers must always monitor the levels of ingredients of their
      products and should be rigorously overseen by governmental regulatory agencies,
      as is done in the pharmaceutical industry.

PMID- 24298011
TI  - Exercise and insulin resistance in youth: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of obesity and diabetes is increasing
      among children, adolescents, and adults. Although estimates of the efficacy of
      exercise training on fasting insulin and insulin resistance have been provided,
      for adults similar estimates have not been provided for youth. This systematic
      review and meta-analysis provides a quantitative estimate of the effectiveness of
      exercise training on fasting insulin and insulin resistance in children and
      adolescents. METHODS: Potential sources were limited to peer-reviewed articles
      published before June 25, 2013, and gathered from the PubMed, SPORTDiscus,
      Physical Education Index, and Web of Science online databases. Analysis was
      limited to randomized controlled trials by using combinations of the terms
      adolescent, child, pediatric, youth, exercise training, physical activity,
      diabetes, insulin, randomized trial, and randomized controlled trial. The authors
      assessed 546 sources, of which 4.4% (24 studies) were eligible for inclusion.
      Thirty-two effects were used to estimate the effect of exercise training on
      fasting insulin, with 15 effects measuring the effect on insulin resistance.
      Estimated effects were independently calculated by multiple authors, and
      conflicts were resolved before calculating the overall effect. RESULTS: Based on
      the cumulative results from these studies, a small to moderate effect was found
      for exercise training on fasting insulin and improving insulin resistance in
      youth (Hedges' d effect size = 0.48 [95% confidence interval: 0.22-0.74], P <
      .001 and 0.31 [95% confidence interval: 0.06-0.56], P < .05, respectively).
      CONCLUSIONS: These results support the use of exercise training in the prevention
      and treatment of type 2 diabetes.

PMID- 24298010
TI  - Addressing the mental health needs of pregnant and parenting adolescents.
AB  - Adolescent parenthood is associated with a range of adverse outcomes for young
      mothers, including mental health problems such as depression, substance abuse,
      and posttraumatic stress disorder. Teen mothers are also more likely to be
      impoverished and reside in communities and families that are socially and
      economically disadvantaged. These circumstances can adversely affect maternal
      mental health, parenting, and behavior outcomes for their children. In this
      report, we provide an overview of the mental health challenges associated with
      teen parenthood, barriers that often prevent teen mothers from seeking mental
      health services, and interventions for this vulnerable population that can be
      integrated into primary care services. Pediatricians in the primary care setting
      are in a unique position to address the mental health needs of adolescent parents
      because teens often turn to them first for assistance with emotional and
      behavioral concerns. Consequently, pediatricians can play a pivotal role in
      facilitating and encouraging teen parents' engagement in mental health treatment.

PMID- 24298012
TI  - Opposing immunomodulatory roles of prostaglandin D2 during the progression of
      skin inflammation.
AB  - The effects of PGD2 are extremely context dependent. It can have pro- or anti
      inflammatory effects in clinically important pathological conditions. A greater
      mechanistic insight into the determinants of PGD2 activity during inflammation is
      thus required. In this study, we investigated the role of PGD2 in croton oil
      induced dermatitis using transgenic (TG) mice overexpressing hematopoietic PGD
      synthase. Administration of croton oil caused tissue swelling and vascular
      leakage in the mouse ear. Compared with wild-type animals, TG mice produced more
      PGD2 and showed decreased inflammation in the early phase, but more severe
      manifestations during the late phase. Data obtained from bone marrow
      transplantation between wild-type and TG mice indicated that PGD2 produced by
      tissue resident cells in the TG mice attenuated early-phase inflammation, whereas
      PGD2 produced from hematopoietic lineage cells exacerbated late-phase
      inflammation. There are two distinct PGD2 receptors: D-prostanoid receptor (DP)
      and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2).
      In TG mice, treatment with a DP antagonist exacerbated inflammation in the early
      phase, whereas treatment with a CRTH2 antagonist attenuated inflammation during
      the late phase. In vitro experiments showed that DP agonism enhanced vascular
      endothelial barrier formation, whereas CRTH2 agonism stimulated neutrophil
      migration. Collectively, these results show that when hematopoietic PGD synthase
      is overexpressed, tissue resident cell-derived PGD2 suppresses skin inflammation
      via DP in the early phase, but hematopoietic lineage cell-derived PGD2 stimulates
      CRTH2 and promotes inflammation during the late phase. DP-mediated vascular
      barrier enhancement or CRTH2-mediated neutrophil activation may be responsible
      for these effects. Thus, PGD2 represents opposite roles in inflammation,
      depending on the disease phase in vivo. 

PMID- 24298013
TI  - Qualitatively different T cell phenotypic responses to IL-2 versus IL-15 are
      unified by identical dependences on receptor signal strength and duration.
AB  - IL-2 and IL-15 are common gamma-chain family cytokines involved in regulation of
      T cell differentiation and homeostasis. Despite signaling through the same
      receptors, IL-2 and IL-15 have non-redundant roles in T cell biology, both
      physiologically and at the cellular level. The mechanisms by which IL-2 and IL-15
      trigger distinct phenotypes in T cells remain elusive. To elucidate these
      mechanisms, we performed a quantitative comparison of the phosphotyrosine
      signaling network and resulting phenotypes triggered by IL-2 and IL-15. This
      study revealed that the signaling networks activated by IL-2 or IL-15 are highly
      similar and that T cell proliferation and metabolism are controlled in a
      quantitatively distinct manner through IL-2/15R signal strength independent of
      the cytokine identity. Distinct phenotypes associated with IL-2 or IL-15
      stimulation therefore arise through differential regulation of IL-2/15R signal
      strength and duration because of differences in cytokine-receptor binding
      affinity, receptor expression levels, physiological cytokine levels, and cytokine
      receptor intracellular trafficking kinetics. These results provide important
      insights into the function of other shared cytokine and growth factor receptors,
      quantitative regulation of cell proliferation and metabolism through signal
      transduction, and improved design of cytokine based clinical immunomodulatory
      therapies for cancer and infectious diseases. 

PMID- 24298014
TI  - TGF-beta-mediated Foxp3 gene expression is cooperatively regulated by Stat5,
      Creb, and AP-1 through CNS2.
AB  - Foxp3 plays an important role in the development and the function of regulatory T
      cells (Treg). Both the induction and maintenance of Foxp3 gene expression are
      controlled by several regulatory regions including two enhancers in the conserved
      noncoding sequences (CNS). The functions of Enhancer 1 in CNS1 are well
      established, whereas those of Enhancer 2 in CNS2 remain unclear. Although CNS2
      contains enhancer activity, methylated CpG sequences in this region prevent Foxp3
      gene expression in Foxp3(-) T cells. These sequences are, however, demethylated
      in Foxp3(+) Treg by mechanisms as yet unknown. To investigate the role of CNS2,
      we have determined the Enhancer 2 core sequence by luciferase reporter assays in
      the absence of methylation to exclude the inhibitory effect and shown that
      transcription factors AP-1, Stat5, and Creb cooperate in regulating Enhancer 2
      activity. We have then determined the methylation sensitivity of each of the
      transcription factors. AP-1 was found to be methylation sensitive as has
      previously been described for Creb. However, Stat5 was active even when its
      binding site in CNS2 was methylated. Stat5 binding to Enhancer 2 occurred early
      and preceded that of AP-1 and Creb during Treg induction. In addition, Stat5
      activation is itself dependent on TGF-beta signaling through Smad3-mediated
      blockade of Socs3 expression. These findings suggest that Stat5 is a key
      regulator for opening up the CNS2 region during induced Treg induction, whereas
      AP-1 and Creb maintain Enhancer 2 activity. 

PMID- 24298016
TI  - Unexpected observations--a tribute to Christian de Duve (1917-2013).

PMID- 24298015
TI  - The role of NOD2 in murine and human melioidosis.
AB  - Nucleotide-binding oligomerization domain 2 (NOD2) is a cytosolic pathogen
      recognition receptor that regulates susceptibility to a variety of infections and
      chronic diseases. Burkholderia pseudomallei, a facultative intracellular
      bacterium, causes the tropical infection melioidosis. We hypothesized that NOD2
      may participate in host defense in melioidosis. We performed a series of in vitro
      assays and in vivo experiments and analyzed the association of human genetic
      variation with infection to delineate the contribution of NOD2 to the host
      response to B. pseudomallei. We found that transfection with NOD2 mediated NF
      kappaB activation induced by B. pseudomallei stimulation of HEK293 cells. After
      low-dose inoculation with aerosolized B. pseudomallei, Nod2-deficient mice showed
      impaired clinical responses and permitted greater bacterial replication in the
      lung and dissemination to the spleen compared with wild-type mice. IL-6 and KC
      levels were higher in the lungs of Nod2-deficient mice. In a cohort of 1562 Thai
      subjects, a common genetic polymorphism in the NOD2 region, rs7194886, was
      associated with melioidosis, and this effect was most pronounced in women.
      rs7194886 was not associated with differences in cytokine production induced by
      whole-blood stimulation with the NOD2 ligand, muramyl dipeptide, or B.
      pseudomallei. To our knowledge, these findings are the first to characterize the
      role of NOD2 in host defense in mammalian melioidosis. 

PMID- 24298017
TI  - Protein kinase Cepsilon-calcineurin cosignaling downstream of toll-like receptor
      4 downregulates fibrosis and induces wound healing gene expression in cardiac
      myofibroblasts.
AB  - The pathways which regulate resolution of inflammation and contribute to positive
      remodeling of the myocardium following injury are poorly understood. Here we show
      that protein kinase C epsilon (PKCepsilon) cooperates with the phosphatase
      calcineurin (CN) to potentiate induction of cardioprotective gene expression
      while suppressing expression of fibrosis markers. This was achieved by detailed
      analysis of the regulation of cyclooxygenase 2 (COX-2) expression as a marker
      gene and by using gene expression profiling to identify genes regulated by
      coexpression of CN-Aalpha/PKCepsilon in adult rat cardiac myofibroblasts (ARVFs)
      on a larger scale. GeneChip analysis of CN-Aalpha/PKCepsilon-coexpressing ARVFs
      showed that COX-2 provides a signature for wound healing and is associated with
      downregulation of fibrosis markers, including connective tissue growth factor
      (CTGF), fibronectin, and collagens Col1a1, Col3a1, Col6a3, Col11a1, Col12a1, and
      Col14a1, with concomitant upregulation of cardioprotection markers, including COX
      2 itself, lipocalin 2 (LCN2), tissue inhibitor of metalloproteinase 1 (TIMP-1),
      interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS). In primary rat
      cardiomyocyte cultures Toll-like receptor 4 (TLR4) agonist- or PKCepsilon/CN
      dependent COX-2 induction occurred in coresident fibroblasts and was blocked by
      selective inhibition of CN or PKC alpha/epsilon or elimination of fibroblasts.
      Furthermore, ectopic expression of PKCepsilon and CN in ARVFs showed that the
      effects on COX-2 expression are mediated by specific NFAT sites within the COX-2
      promoter as confirmed by site-directed mutagenesis and chromatin
      immunoprecipitation (ChIP). Therefore, PKCepsilon may negatively regulate adverse
      myocardial remodeling by cooperating with CN to downregulate fibrosis and induce
      transcription of cardioprotective wound healing genes, including COX-2. 

PMID- 24298018
TI  - Galphai2 signaling is required for skeletal muscle growth, regeneration, and
      satellite cell proliferation and differentiation.
AB  - We have previously shown that activation of Galphai2, an alpha subunit of the
      heterotrimeric G protein complex, induces skeletal muscle hypertrophy and
      myoblast differentiation. To determine whether Galphai2 is required for skeletal
      muscle growth or regeneration, Galphai2-null mice were analyzed. Galphai2
      knockout mice display decreased lean body mass, reduced muscle size, and impaired
      skeletal muscle regeneration after cardiotoxin-induced injury. Short hairpin RNA
      (shRNA)-mediated knockdown of Galphai2 in satellite cells (SCs) leads to
      defective satellite cell proliferation, fusion, and differentiation ex vivo. The
      impaired differentiation is consistent with the observation that the myogenic
      regulatory factors MyoD and Myf5 are downregulated upon knockdown of Galphai2.
      Interestingly, the expression of microRNA 1 (miR-1), miR-27b, and miR-206, three
      microRNAs that have been shown to regulate SC proliferation and differentiation,
      is increased by a constitutively active mutant of Galphai2 [Galphai2(Q205L)] and
      counterregulated by Galphai2 knockdown. As for the mechanism, this study
      demonstrates that Galphai2(Q205L) regulates satellite cell differentiation into
      myotubes in a protein kinase C (PKC)- and histone deacetylase (HDAC)-dependent
      manner. 

PMID- 24298019
TI  - Notch-Nrf2 axis: regulation of Nrf2 gene expression and cytoprotection by notch
      signaling.
AB  - The Notch signaling pathway enables regulation and control of development,
      differentiation, and homeostasis through cell-cell communication. Our
      investigation shows that Notch signaling directly activates the Nrf2 stress
      adaptive response pathway through recruitment of the Notch intracellular domain
      (NICD) transcriptosome to a conserved Rbpjkappa site in the promoter of Nrf2.
      Stimulation of Notch signaling through Notch ligand expression in cells and by
      overexpression of the NICD in Rosa(NICD/-)::AlbCre mice in vivo induces
      expression of Nrf2 and its target genes. Continuous and transient NICD expression
      in the liver produces a Notch-dependent cytoprotective response through direct
      transcriptional activation of Nrf2 signaling to rescue mice from acute
      acetaminophen toxicity. This response can be reversed upon genetic disruption of
      Nrf2. Morphological studies showed that the characteristic phenotype of high
      density intrahepatic bile ducts and enlarged liver in Rosa(NICD/-)::AlbCre mice
      could be at least partially reversed after Nrf2 disruption. Furthermore, the
      liver and bile duct phenotypes could be recapitulated with constitutive
      activation of Nrf2 signaling in Keap1(F/F)::AlbCre mice. It appears that Notch-to
      Nrf2 signaling is another important determinant in liver development and function
      and promotes cell-cell cytoprotective signaling responses. 

PMID- 24298020
TI  - Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via
      negative regulation of the chaperonin TRiC.
AB  - Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ)
      repeats is associated with cytotoxicity in several neurodegenerative disorders,
      including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero
      oligomeric complex has been shown to play an important role in protecting cells
      against the accumulation of misfolded polyQ protein aggregates. It is essential
      to elucidate how TRiC function is regulated to better understand the pathological
      mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2
      (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells,
      overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by
      promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not.
      Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation
      of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of
      TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2
      enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2
      mediated reduction of TRiC protein levels was subsequent to the recruitment of
      COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted
      with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together,
      these results demonstrate that VRK2 is crucial to regulate the ubiquitination
      proteosomal degradation of TRiC, which controls folding of polyglutamine proteins
      involved in Huntington's disease. 

PMID- 24298021
TI  - Acetylation of the transcriptional repressor Ume6p allows efficient promoter
      release and timely induction of the meiotic transient transcription program in
      yeast.
AB  - Differentiation programs require strict spatial and temporal control of gene
      transcription. Genes expressed during meiotic development in Saccharomyces
      cerevisiae display transient induction and repression. Early meiotic gene (EMG)
      repression during mitosis is achieved by recruiting both histone deacetylase and
      chromatin remodeling complexes to their promoters by the zinc cluster DNA binding
      protein Ume6p. Ume6p repression is relieved by ubiquitin-mediated destruction
      that is stimulated by Gcn5p-induced acetylation. In this report, we demonstrate
      that Gcn5p acetylation of separate lysines within the zinc cluster domain
      negatively impacts Ume6p DNA binding. Mimicking lysine acetylation using
      glutamine substitution mutations decreased Ume6p binding efficiency and resulted
      in partial derepression of Ume6p-regulated genes. Consistent with this result,
      molecular modeling predicted that these lysine side chains are adjacent to the
      DNA phosphate backbone, suggesting that acetylation inhibits Ume6p binding by
      electrostatic repulsion. Preventing acetylation did not impact final EMG
      induction levels during meiosis. However, a delay in EMG induction was observed,
      which became more severe in later expression classes, ultimately resulting in
      delayed and reduced execution of the meiotic nuclear divisions. These results
      indicate that Ume6p acetylation ensures the proper timing of the transient
      transcription program during meiotic development. 

PMID- 24298022
TI  - An antibody blocking activin type II receptors induces strong skeletal muscle
      hypertrophy and protects from atrophy.
AB  - The myostatin/activin type II receptor (ActRII) pathway has been identified to be
      critical in regulating skeletal muscle size. Several other ligands, including
      GDF11 and the activins, signal through this pathway, suggesting that the ActRII
      receptors are major regulatory nodes in the regulation of muscle mass. We have
      developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent
      binding of ligands to the receptors and thus inhibit downstream signaling. BYM338
      enhances differentiation of primary human skeletal myoblasts and counteracts the
      inhibition of differentiation induced by myostatin or activin A. BYM338 prevents
      myostatin- or activin A-induced atrophy through inhibition of Smad2/3
      phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338
      dramatically increases skeletal muscle mass in mice, beyond sole inhibition of
      myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse
      version of the antibody induces enhanced muscle hypertrophy in myostatin mutant
      mice, further confirming a beneficial effect on muscle growth beyond myostatin
      inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from
      glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic
      force losses. These data highlight the compelling therapeutic potential of BYM338
      for the treatment of skeletal muscle atrophy and weakness in multiple settings. 

PMID- 24298023
TI  - Characterization and in vivo functional analysis of the Schizosaccharomyces pombe
      ICLN gene.
AB  - During the early steps of snRNP biogenesis, the survival motor neuron (SMN)
      complex acts together with the methylosome, an entity formed by the pICln
      protein, WD45, and the PRMT5 methyltransferase. To expand our understanding of
      the functional relationship between pICln and SMN in vivo, we performed a genetic
      analysis of an uncharacterized Schizosaccharomyces pombe pICln homolog. Although
      not essential, the S. pombe ICln (SpICln) protein is important for optimal yeast
      cell growth. The human ICLN gene complements the Deltaicln slow-growth phenotype,
      demonstrating that the identified SpICln sequence is the bona fide human homolog.
      Consistent with the role of human pICln inferred from in vitro experiments, we
      found that the SpICln protein is required for optimal production of the
      spliceosomal snRNPs and for efficient splicing in vivo. Genetic interaction
      approaches further demonstrate that modulation of ICln activity is unable to
      compensate for growth defects of SMN-deficient cells. Using a genome-wide
      approach and reverse transcription (RT)-PCR validation tests, we also show that
      splicing is differentially altered in Deltaicln cells. Our data are consistent
      with the notion that splice site selection and spliceosome kinetics are highly
      dependent on the concentration of core spliceosomal components. 

PMID- 24298024
TI  - Stimulation of the alpha7 nicotinic acetylcholine receptor protects against
      sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation.
AB  - BACKGROUND: The Toll-like receptor (TLR) plays an important role in the induction
      of the hyperinflammatory response and tissue injury in sepsis. The cholinergic
      antiinflammatory pathway serves as a link between the parasympathetic and innate
      immune systems. We examined the antiinflammatory effect of nicotine, a potent
      alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonist, with regard to TLR
      expression and signaling during sepsis. METHODS: Polymicrobial sepsis was induced
      in mice by cecal ligation and puncture (CLP). The subjects received
      intraperitoneal nicotine (400 MUg/kg) immediately after CLP for the biochemical
      study and 0, 24, 48, and 72 hours after CLP for the survival test.
      Intraperitoneal methyllycaconitine (MLA; 5 mg/kg), an alpha7nAChR antagonist, was
      administered 5 minutes prior to nicotine treatment. We evaluated the effects of
      nicotine using alpha7nAChR and phosphoinositide 3-kinase (PI3K) inhibitors in
      lipopolysaccharide-stimulated RAW264.7 cells. RESULTS: Nicotine improved sepsis
      induced mortality, attenuated organ failure, and suppressed inflammatory
      cytokines, which were abolished by MLA. Nicotine enhanced PI3K/Akt activation and
      reduced PU.1 activity and TLR4 expression. MLA and PI3K inhibitors blocked this
      effect of nicotine. CONCLUSIONS: Our findings suggest that stimulation of the
      cholinergic antiinflammatory pathway by nicotine protects against septic injury
      and that this may be associated with inhibition of TLR4 expression via
      alpha7nAChR/PI3K signaling.

PMID- 24298025
TI  - Combining calcium imaging with other optical techniques.
AB  - Ca(2+) imaging is a commonly used approach for measuring Ca(2+) signals at high
      spatial resolution. The method is often combined with electrode recordings to
      correlate electrical and chemical signals or to investigate Ca(2+) signals
      following an electrical stimulation. To obtain information on electrical activity
      at the same spatial resolution, Ca(2+) imaging must be combined with membrane
      potential imaging. Similarly, stimulation of subcellular compartments requires
      photostimulation. Thus, combining Ca(2+) imaging with an additional optical
      technique facilitates the study of a number of physiological questions. The aim
      of this article is to introduce some basic principles regarding the combination
      of Ca(2+) imaging with other optical techniques. We discuss the design of the
      optics, the design of experimental protocols, the optical characteristics of
      Ca(2+) indicators used in combination with an optical probe, and the affinity of
      the Ca(2+) indicator in relation to the type of measurement. This information
      will enable the reader to devise an optimal strategy for combined optical
      experiments.

PMID- 24298026
TI  - Transgenic mouse models--a seminal breakthrough in oncogene research.
AB  - Transgenic mouse models are an integral part of modern cancer research, providing
      a versatile and powerful means of studying tumor initiation and progression,
      metastasis, and therapy. The present repertoire of these models is very diverse,
      with a wide range of strategies used to induce tumorigenesis by expressing
      dominant-acting oncogenes or disrupting the function of tumor-suppressor genes,
      often in a highly tissue-specific manner. Much of the current technology used in
      the creation and characterization of transgenic mouse models of cancer will be
      discussed in depth elsewhere. However, to gain a complete appreciation and
      understanding of these complex models, it is important to review the history of
      the field. Transgenic mouse models of cancer evolved as a new and, compared with
      the early cell-culture-based techniques, more physiologically relevant approach
      for studying the properties and transforming capacities of oncogenes. Here, we
      will describe early transgenic mouse models of cancer based on tissue-specific
      expression of oncogenes and discuss their impact on the development of this still
      rapidly growing field.

PMID- 24298027
TI  - Combining Ca2+ and membrane potential imaging in single neurons.
AB  - The ability to monitor Ca(2+) signals and membrane potential simultaneously at
      multiple locations on the same neuron facilitates further progress in our
      understanding of neuronal function. In particular, this method allows correlation
      of electrical and chemical signals from multiple sites, including those
      inaccessible to microelectrodes. This protocol describes a procedure for loading
      cells with two indicators, a Ca(2+)-sensitive Fura dye and voltage-sensitive
      JPW1114, together with the equipment required for detecting and imaging the two
      signals. Potential problems are discussed as well as the capabilities and
      limitations of the technique.

PMID- 24298028
TI  - Combining Ca2+ imaging with -glutamate photorelease.
AB  - This article describes simple configurations and methods for measuring optical
      Ca(2+) signals in response to photorelease of -glutamate. This photostimulation
      allows activation of postsynaptic glutamate receptors without activation of
      voltage-gated Ca(2+) channels, thereby permitting the separation and analysis of
      different Ca(2+) components. We give details of basic microscopy configurations
      and recommend tools for efficiently illuminating the preparation while preserving
      the healthy condition of the tissue. We also suggest methodological procedures
      and discuss linear optics for achieving simultaneous imaging and uncaging using
      two-photon illumination.

PMID- 24298030
TI  - Ultraviolet photochemical cross-linking to detect RNA-binding proteins.
AB  - RNA is photoreactive on exposure to ultraviolet (UV) light in the 250- to 270-nm
      range. On UV treatment, RNA bases absorb energy to generate free radicals that
      can covalently attach to nearby amino acid residues in RNA-bound proteins. UV
      cross-linking experiments have been extensively used to identify and characterize
      RNA-binding proteins. The method described here involves the use of (32)P-labeled
      RNA and crude extracts or purified proteins.

PMID- 24298029
TI  - RNA sequencing by primer extension.
AB  - Direct sequencing of RNA by primer extension is a fast and accurate method that
      is useful in a variety of situations. It is a valuable technique for determining
      the faithfulness of in vitro processing reactions, such as splicing or RNA
      editing. It is often used as an alternative to reverse transcription PCR (RT-PCR)
      followed by cloning and DNA sequencing. In the primer extension reaction, a
      radiolabeled probe (almost always a 5'-end-labeled DNA oligonucleotide) is
      annealed to the target RNA of interest. After hybridization, cDNA synthesis by
      reverse transcription proceeds from the 3' end of the primer in the presence of
      chain-terminating dideoxynucleotide triphosphates. The cDNA products are
      fractionated on denaturing polyacrylamide gels and analyzed by phosphorimaging or
      autoradiography.

PMID- 24298031
TI  - Preparing size markers for gel electrophoresis.
AB  - Here we present two simple methods for preparing radiolabeled size markers for
      gel electrophoresis. The first procedure describes the generation of an RNA
      marker ladder by the alkaline hydrolysis of (32)P 5'- or 3'-end-labeled RNA. The
      second procedure describes the labeling of DNA fragments produced by digestion of
      pBR322 with the restriction enzyme MspI.

PMID- 24298032
TI  - Infrared video microscopy for visualizing neurons and neuronal excitation in
      brain slices.
AB  - Here we describe methods for imaging neurons and neuronal excitation in brain
      slices with infrared video microscopy. Patch clamping in conjunction with a
      gradient-contrast system allows electrical recording from fine neuronal
      processes. Imaging with an infrared (IR)-darkfield system allows visualization of
      the intrinsic optical signal (IOS).

PMID- 24298033
TI  - Making mosaic fish primordia by focal electroporation.
AB  - The lateral line is a mechanosensory system that comprises a set of discrete
      sense organs called neuromasts, which are arranged in reproducible patterns on
      the surface of fish and amphibians. The posterior component of the system, the
      posterior lateral line (PLL), comprises the neuromasts on the body and tail. It
      develops from the migrating primordium and so can be used to examine various
      aspects of neural development, including the control of long-range, collective
      cell migration and the mechanisms underlying the establishment of appropriate
      connectivity. Mosaic animals are those in which one or a few cells differ
      genetically from all others. Several methods have been developed to generate
      mosaic zebrafish, which can be used in long-term fate mapping or lineage tracing
      experiments if the progenitor cell stably expresses a reporter gene such as green
      fluorescent protein. Mosaic analysis can also be used to evaluate the cell
      autonomy of a given mutation, confronting mutant and wild-type cells, or two
      different types of mutant cells, in morphogenetic mosaics. Here we present an
      application of electroporation, which is designed to generate mosaics in defined
      parts of the developing zebrafish PLL. The method is based on the idea of focal
      electroporation, a technique developed to introduce dyes and constructs into
      cells within intact tissues. Current is forced into the embryo by sealing the tip
      of the electrode against the enveloping cells (periderm or ectoderm depending on
      the developmental stage, or mantle cells in the case of neuromasts).

PMID- 24298034
TI  - Labeling hair cells and afferent neurons in the posterior lateral-line system of
      zebrafish.
AB  - The lateral line is a mechanosensory system that comprises a set of discrete
      sense organs called neuromasts, which are arranged in reproducible patterns on
      the surface of fish and amphibians. The posterior component of the system, the
      posterior lateral line, comprises the neuromasts on the body and tail. Each
      neuromast has a core of mechanosensory hair cells, each of which is depolarized
      by water motion in one direction and hyperpolarized by motion in the other
      direction, thereby enabling fish to extract information from the movements of
      water around their body. Neuromasts are innervated by a few afferent neurons
      (usually two, but sometimes more), which have their cell bodies clustered in
      cranial ganglia and project their central axons to the hindbrain, where they
      extend longitudinally along all rhombomeres. Hair cells are readily labeled by
      small cationic styryl pyridinium dyes such as DiASP. Afferent fibers are also
      progressively labeled with this dye, presumably by trans-synaptic uptake.
      Adjusting the dye concentration and incubation time can lead to the labeling of
      the entire afferent system, thereby providing a fast and easy method for
      visualizing the central projection in the hindbrain of live fish. The simplicity
      of the method makes it potentially useful for screens based on forward or reverse
      genetic approaches. Here we present protocols for labeling hair cells in live
      zebrafish and for labeling afferent neurons in zebrafish embryos.

PMID- 24298035
TI  - Labeling second-order sensory neurons in the posterior lateral-line system of
      zebrafish.
AB  - The lateral line is a mechanosensory system that comprises a set of discrete
      sense organs called neuromasts, which are arranged in reproducible patterns on
      the surface of fish and amphibians. The posterior component of the system, the
      posterior lateral line (PLL), comprises the neuromasts on the body and tail and
      has its ganglion just posterior to the otic vesicle. The peripheral location of
      the PLL system makes it accessible and easily visualized by imaging methods.
      Neuromasts are innervated by a few afferent neurons (usually two, but sometimes
      more), which have their cell bodies clustered in cranial ganglia and project
      their central axons to the hindbrain, where they extend longitudinally along all
      rhombomeres. Positively charged lipophilic carbocyanine dyes, such as DiI, have
      traditionally been used to label neurons, as described here. This method is
      especially useful for the analysis of PLL innervation because injection of the
      dye into a neuromast leads to specific labeling of the afferent neurons. The
      method can also be used to follow the flow of PLL information to higher central
      nervous system levels by first labeling the central projection of chosen afferent
      neurons and then making a second injection of DiI within the synaptic field to
      label the second-order neurons that extend dendrites to this field.

PMID- 24298036
TI  - Imaging microglia in brain slices and slice cultures.
AB  - Here we describe a method for imaging fluorescently labeled parenchymal microglia
      (MG) in excised neonatal or adult rodent brain tissue slices. Using multichannel
      confocal or two-photon time-lapse imaging, the approach affords real-time
      analyses of MG behaviors, including motility, migration, chemotaxis,
      proliferation, and phagocytosis in live brain tissues. The method is applicable
      to acutely prepared tissue slices from developing and adult rodents and to slice
      cultures derived from neonatal rodents, including transgenic and green
      fluorescent protein reporter mice. A variety of fluorescent tags can be used to
      study the structure and physiology of MG in these preparations. Moreover, bath
      application of reagents (such as ATP) can establish spatial and temporal
      gradients that induce chemokinesis- and chemotaxis-like MG migration in tissue
      slices. Thus, the approach is useful for dissecting the molecular basis of MG
      behaviors and testing whether candidate reagents alter MG behavior and function
      in semi-intact central nervous system tissue preparations.

PMID- 24298037
TI  - Uncaging calcium in neurons.
AB  - Changes in intracellular free calcium concentration (Delta[Ca(2+)]i) driving
      physiological events such as neurotransmitter release or Ca(2+)-dependent
      currents can be monitored using Ca(2+)-sensitive fluorescent dyes. Although these
      dyes can correlate Delta[Ca(2+)]i with a physiological event, they cannot
      directly test for causality between changes in [Ca(2+)]i and that event.
      Photolabile Ca(2+) chelators are Ca(2+)-binding molecules that can alter and, to
      a certain extent, control [Ca(2+)]i in an inducible manner and with temporal and
      spatial resolution that surpasses microinjection or ionophore application. Here
      we discuss the properties of caged Ca(2+) compounds as well as some practical
      considerations for their use in neuronal cells, where they have proven
      particularly effective.

PMID- 24298038
TI  - Optically induced occlusion of single blood vessels in rodent neocortex.
AB  - The ability to form targeted vascular occlusions in small vessels of the brain is
      an important technique for studying the microscopic basis of cerebral ischemia.
      We describe two complementary methods that enable targeted occlusion of any
      single blood vessel within the upper 500 um of adult rodent neocortex. Our goal
      is to generate highly localized regions of ischemia by blocking penetrating
      arterioles and ascending venules, which are bottlenecks of flow in the cortical
      angioarchitecture. One method, termed photothrombosis, makes use of linear
      optical absorption by a photosensitizer, transiently circulated in the blood
      stream, to induce a clot in a surface or near-surface segment of a vessel. The
      second method, termed plasma-mediated ablation, makes use of nonlinear optical
      interactions, without the need to introduce an exogenous absorber, to induce
      clots in subsurface segments of penetrating vessels, as well as subsurface
      microvessels and capillaries. The choice of the method for occlusion of
      individual vessels depends on the location of the vessels being studied and the
      objectives of the study. Here we describe concurrent high resolution in vivo
      imaging and auxiliary laser setups, occlusion protocols, and post hoc
      histological procedures.

PMID- 24298039
TI  - Spatial light modulator microscopy.
AB  - The use of spatial light modulators (SLMs) for two-photon laser microscopy is
      described. SLM phase modulation can be used to generate nearly any spatiotemporal
      pattern of light, enabling simultaneous illumination of any number of selected
      regions of interest. We take advantage of this flexibility to perform fast two
      photon imaging or uncaging experiments on dendritic spines and neocortical
      neurons. By operating in the spatial Fourier plane, an SLM can effectively mimic
      any arbitrary optical transfer function and thus replace, in software, many of
      the functions provided by hardware in standard microscopes, such as focusing,
      magnification, and aberration correction.

PMID- 24298040
TI  - Methods for the detection of peptidylarginine deiminase (PAD) activity and
      protein citrullination.
AB  - The post-translational conversion of peptidylarginine to peptidylcitrulline, a
      process also known as citrullination, is catalyzed by the enzyme family of
      peptidylarginine deiminases (PADs) and has been demonstrated to be involved in
      many physiological processes, including the regulation of gene expression. In
      addition, citrullination has been shown to be associated with several diseases,
      such as cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's
      disease. To get more insight into the role of PAD enzymes and citrullination in
      both health and disease, experimental strategies to study PAD activity and to
      characterize citrullinated proteins in complex biological samples are crucial.
      Here, we describe the chemical, proteomic and antibody-based procedures that are
      currently available and discuss their applicability for the analysis of complex
      samples. The methods that have been developed can be used to provide more insight
      in the substrate specificity of PAD enzymes. Because the evidence that PADs play
      a pathophysiological role in the diseases mentioned above is increasing, they
      become attractive targets for therapeutic interventions. More knowledge of PAD
      specificity and the availability of reliable, high-throughput assays for PAD
      activity will facilitate the development of highly specific PAD inhibitors. 

PMID- 24298041
TI  - Final results of a phase II study of S-1 in patients with cytokine-refractory
      metastatic renal cell carcinoma.
AB  - OBJECTIVE: A planned primary analysis of a Phase II study of S-1 demonstrated
      that the drug was active and tolerable in Japanese patients with cytokine
      refractory metastatic renal cell carcinoma. Furthermore, pharmacogenomic analysis
      suggested that low expression of thymidylate synthase mRNA may have been
      associated with clinical outcome in terms of overall response rate and
      progression-free survival. Here, we report the results of the final analysis
      assessing the efficacy and safety of S-1 including overall survival. METHODS:
      Patients with renal cell carcinoma were eligible if they had had at least one
      regimen of cytokine for metastatic disease. S-1 was orally administered on Days 1
      28 of a 42-day cycle until disease progression. The primary endpoint was the
      overall response rate, and the secondary endpoint included progression-free
      survival, overall survival and safety. RESULTS: A total of 45 patients were
      treated with S-1 and were fully assessable for efficacy and safety. At the final
      analysis, a response was seen in 11 patients (overall response rate, 24.4%; 95%
      confidence interval: 12.9-39.5%), including two patients who achieved a complete
      response. The final median progression-free and overall survival were 9.2 and
      42.8 months, respectively. The safety profile of S-1 was favorable. It was
      suggested that there was no relation between overall survival and the expression
      level of thymidylate synthase. CONCLUSION: This final analysis confirms that S-1
      treatment is effective and safe in patients with cytokine-refractory renal cell
      carcinoma.

PMID- 24298042
TI  - Health-related quality of life among cancer survivors in Korea: the Korea
      National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: The purpose of this study was to investigate the quality of life among
      cancer survivors compared with individuals without a history of cancer (noncancer
      controls) using the Korea National Health and Nutrition Examination Survey.
      METHODS: The study subjects were 783 adult cancer survivors and 36 456 noncancer
      controls who participated in the third, fourth and fifth Korea National Health
      and Nutrition Examination Survey. Demographic factors, health-related behavior,
      clinical characteristics and health-related quality of life were assessed with
      self-reported questionnaires. The EuroQoL-5Dimension was used to evaluate health
      related quality of life. Descriptive statistics and multiple regression analysis
      were used to compare health-related quality of life between cancer survivors and
      noncancer controls. RESULTS: About 67% were women and the mean age of the cancer
      survivors was 60.9 +/- 12.4 years. About 52% of survivors were diagnosed with
      cancer between 45 and 64 years, and more than half of cancer survivors were
      diagnosed 5 years or less before the interview. The pain/discomfort dimension was
      the highest reported problem: 43.6% for cancer survivors. The proportion of any
      reported problem was significantly higher among cancer survivors compared with
      noncancer controls in terms of mobility (adjusted odds ratio (aOR), 1.56, 95%
      confidence interval, 1.24-1.97), usual activities (aOR, 1.45, 95% confidence
      interval, 1.11-1.89), pain/discomfort (aOR, 1.26, 95% confidence interval, 1.04
      1.52) and anxiety/depression (aOR, 1.61, 95% confidence interval, 1.29-2.01).
      CONCLUSIONS: Cancer survivors had a significantly lower quality of life compared
      with noncancer controls. The pain/discomfort dimension was the highest reported
      problem in cancer survivors.

PMID- 24298043
TI  - From lecture halls to cinema screens: learning about the psyche through films.

PMID- 24298045
TI  - Low-dose effects of bisphenol A on early sexual development in male and female
      rats.
AB  - Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been
      reported to impair many endpoints for reproductive and neurological development;
      however, it is controversial whether BPA has effects in the microgram per
      kilogram dose range. The aim of the current study was to examine the influence of
      BPA on early sexual development in male and female rats at dose levels covering
      both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per
      day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25
      mg/kg bw per day). Time-mated Wistar rats (n=22) were gavaged during pregnancy
      and lactation from gestation day 7 to pup day 22 with 0, 0.025, 0.25, 5 or 50
      mg/kg bw per day BPA. From 0.250 mg/kg and above, male anogenital distance (AGD)
      was significantly decreased, whereas decreased female AGD was seen from 0.025
      mg/kg bw per day and above. Moreover, the incidence of nipple retention in males
      appeared to increase dose relatedly and the increase was statistically
      significant at 50 mg/kg per day. No significant changes in reproductive organ
      weights in the 16-day-old males and females and no signs of maternal toxicity
      were seen. The decreased AGD at birth in both sexes indicates effects on prenatal
      sexual development and provides new evidence of low-dose adverse effects of BPA
      in rats in the microgram per kilogram dose range. The NOAEL in this study is
      clearly below 5 mg/kg for BPA, which is used as the basis for establishment of
      the current tolerable daily intake (TDI) by EFSA; thus a reconsideration of the
      current TDI of BPA appears warranted. 

PMID- 24298046
TI  - Mixtures of endocrine-disrupting contaminants induce adverse developmental
      effects in preweaning rats.
AB  - Reproductive toxicity was investigated in rats after developmental exposure to a
      mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic
      and cosmetic ingredients, and paracetamol. The mixture was composed on the basis
      of information about high-end human exposures, and the dose levels reflecting
      100, 200, and 450 times this exposure were tested. The compounds were also
      grouped according to their estrogenicity or anti-androgenicity, and their joint
      effects were tested at two different doses, with each group reflecting 200 or 450
      times human exposure. In addition, a single paracetamol dose was tested (350
      mg/kg per day). All exposures and a vehicle were administered by oral gavage to
      time-mated Wistar dams rats throughout gestation and lactation, and their
      offspring were assessed for reproductive effects at birth and in prepuberty. The
      mixture doses, which included the anti-androgenic compounds, affected the male
      offspring by causing decreased anogenital distance, increased nipple retention
      (NR), and reduced ventral prostate weights, at both medium and high doses. In
      addition, the weights of the levator ani/bulbocavernosus muscle (LABC) were
      decreased at the high dose of anti-androgen mixture. No effects were seen after
      exposure to the estrogenic chemicals alone, whereas males exposed solely to
      paracetamol showed decreased LABC weights and increased NR. Thus adverse
      reproductive effects were observed at mixtures reflecting 200 times high-end
      human exposure, which is relatively close to the safety margin covered by the
      regulatory uncertainty factor of 100. This suggests that highly exposed human
      population groups may not be sufficiently protected against mixtures of endocrine
      disrupting chemicals. 

PMID- 24298047
TI  - Germ cell loss is associated with fading Lin28a expression in a mouse model for
      Klinefelter's syndrome.
AB  - Klinefelter's syndrome is a male sex-chromosomal disorder (47,XXY), causing
      hypogonadism, cognitive and metabolic deficits. The majority of patients are
      infertile due to complete germ cell loss after puberty. As the depletion occurs
      during development, the possibilities to study the underlying causes in humans
      are limited. In this study, we used the 41,XX(Y*) mouse model to characterise the
      germ line postnatally. We examined marker expression of testicular cells focusing
      on the spermatogonial stem cells (SSCs) and found that the number of germ cells
      was approximately reduced fivefold at day 1pp in the 41,XX(Y*) mice, indicating
      the loss to start prenatally. Concurrently, immunohistochemical SSC markers
      LIN28A and PGP9.5 also showed decreased expression on day 1pp in the 41,XX(Y*)
      mice (48.5 and 38.9% of all germ cells were positive), which dropped to 7.8 and
      7.3% on 3dpp, and were no longer detectable on days 5 and 10pp respectively. The
      differences in PCNA-positive proliferating cells in XY* and XX(Y*) mice
      dramatically increased towards day 10pp. The mRNA expression of the germ cell
      markers Lin28a (Lin28), Pou5f1 (Oct4), Utf1, Ddx4 (Vasa), Dazl, and Fapb1 (Sycp3)
      was reduced and the Lin28a regulating miRNAs were deregulated in the 41,XX(Y*)
      mice. We suggest a model for the course of germ cell loss starting during the
      intrauterine period. Neonatally, SSC marker expression by the already lowered
      number of spermatogonia is reduced and continues fading during the first
      postnatal week, indicating the surviving cells of the SSC population to be
      disturbed in their stem cell characteristics. Subsequently, the entire germ line
      is then generally lost when entering meiosis.

PMID- 24298048
TI  - Post-testicular sperm maturation and identification of an epididymal protein in
      the Japanese quail (Coturnix coturnix japonica).
AB  - The role of the avian epididymis in post-testicular development and capacitation
      was examined to assess whether avian spermatozoa undergo any processes similar to
      those characteristic of mammalian sperm development. We found no evidence of a
      need for quail sperm to undergo capacitation and 90% of testicular sperm could
      bind to a perivitelline membrane and acrosome react. However, computer-assisted
      sperm analysis showed that 20% of testicular sperm from the quail were capable of
      movement and only about 12% of the motile sperm would have a curvilinear velocity
      greater than the mean for sperm from the distal epididymis. Nevertheless,
      epididymal transit was associated with increases in mean sperm velocity and the
      proportion of motile sperm. Together, these findings explain why earlier workers
      have achieved some fertilizations following inseminations of testicular
      spermatozoa and also demonstrate the need for some epididymal maturation of avian
      spermatozoa. Analysis of the electrophoretic profile of quail epididymal luminal
      proteins revealed that only one major protein (~16 kDa) is secreted by the
      epididymis and it was virtually the only protein secreted by the ipsilateral
      epididymis following unilateral orchidectomy. Mass spectrometry showed that this
      protein is hemoglobin; this finding was confirmed using anti-hemoglobin
      antibodies. It is suggested that hemoglobin may support sperm metabolism in the
      quail epididymis, aid in motility, and/or serve as an antioxidant. 

PMID- 24298049
TI  - Oropharyngeal and nasopharyngeal sampling for the detection of adolescent
      Streptococcus pneumoniae carriers.
AB  - Monitoring the dynamics of pneumococcal carriage makes it possible to evaluate
      the epidemiological characteristics of Streptococcus pneumoniae disease and the
      theoretical coverage offered by pneumococcal vaccines. It has been demonstrated
      that the nasopharyngeal (NP) sampling of respiratory secretions is superior to
      oropharyngeal (OP) sampling for identifying pneumococci carried by younger
      children, but adult data are conflicting and there are no published studies of
      adolescents. In order to compare the efficiency of OP and NP sampling in
      identifying and quantifying S. pneumoniae carriage in healthy adolescents, 2 swab
      samples were obtained from 530 adolescents aged 15-19 years, the first taken from
      the posterior pharyngeal wall through the mouth (OP) and the second through the
      nose (NP). Bacterial genomic DNA was tested for the autolysin-A-encoding gene
      (lytA) and wzg (cpsA) gene of S. pneumoniae in order to evaluate pneumococcal
      carrier status. All of the positive cases were serotyped. S. pneumoniae was
      identified in 35.8% of the OP swabs and 3.5% of the NP swabs (P<0.0001). The
      serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) were
      found in all but two OP samples (98.9%) and only 64.7% of the NP samples
      (P<0.0001). The most frequently identified PCV13 serotype in both groups was 19F,
      followed by serotypes 5 and 9V. In conclusion, OP sampling appeared significantly
      more effective than NP sampling in identifying and characterizing pneumococcal
      carrier status in adolescents. This suggests that OP sampling should be used when
      evaluating the dynamics of pneumococcal carriage among adolescents and the
      theoretical coverage offered by PCV13.

PMID- 24298050
TI  - Saksenaea erythrospora infection following a serious sailing accident.
AB  - Saksenaea erythrospora is a species of the order Mucorales recently described and
      reported as a cause of human mucormycosis. We report a case of S. erythrospora in
      a man involved in a serious sailing accident causing deep skin and soft tissue
      contamination with soil and water. Direct microscopic examination of the clinical
      sample with Giemsa stains showed hyaline and non-septate hyphae belonging to the
      order Mucorales. Fungal identification was performed by culture of biopsy
      material on SDA, and identification of species by floating an agar block
      containing the fungus in a nutritionally deficient medium consisting of sterile
      distilled water supplemented with 0.05 % yeast extract; and by sequencing the ITS
      region of the rDNA. This is the first report to our knowledge of infection with
      S. erythrospora in Argentina, confirming the presence of this fungus in this
      country. 

PMID- 24298052
TI  - Fbw7 dimerization determines the specificity and robustness of substrate
      degradation.
AB  - The Fbw7 tumor suppressor targets a broad network of proteins for ubiquitylation.
      Here we show critical functions for Fbw7 dimerization in regulating the
      specificity and robustness of degradation. Dimerization enables Fbw7 to target
      substrates through concerted binding to two suboptimal and independent
      recognition sites. Accordingly, an endogenous dimerization-deficient Fbw7
      mutation stabilizes suboptimal substrates. Dimerization increases Fbw7's
      robustness by preserving its function in the setting of mutations that disable
      Fbw7 monomers, thereby buffering against pathogenic mutations. Finally,
      dimerization regulates Fbw7 stability, and this likely involves Fbw7 trans
      autoubiquitylation. Our study reveals novel functions of Fbw7 dimerization and an
      unanticipated complexity in substrate degradation.

PMID- 24298051
TI  - Chromothripsis and beyond: rapid genome evolution from complex chromosomal
      rearrangements.
AB  - Recent genome sequencing studies have identified several classes of complex
      genomic rearrangements that appear to be derived from a single catastrophic
      event. These discoveries identify ways that genomes can be altered in single
      large jumps rather than by many incremental steps. Here we compare and contrast
      these phenomena and examine the evidence that they arise "all at once." We
      consider the impact of massive chromosomal change for the development of diseases
      such as cancer and for evolution more generally. Finally, we summarize current
      models for underlying mechanisms and discuss strategies for testing these models.

PMID- 24298053
TI  - Deregulated origin licensing leads to chromosomal breaks by rereplication of a
      gapped DNA template.
AB  - Deregulated origin licensing and rereplication promote genome instability and
      tumorigenesis by largely elusive mechanisms. Investigating the consequences of
      Early mitotic inhibitor 1 (Emi1) depletion in human cells, previously associated
      with rereplication, we show by DNA fiber labeling that origin reactivation occurs
      rapidly, well before accumulation of cells with >4N DNA, and is associated with
      checkpoint-blind ssDNA gaps and replication fork reversal. Massive RPA chromatin
      loading, formation of small chromosomal fragments, and checkpoint activation
      occur only later, once cells complete bulk DNA replication. We propose that
      deregulated origin firing leads to undetected discontinuities on newly replicated
      DNA, which ultimately cause breakage of rereplicating forks.

PMID- 24298054
TI  - The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal
      promoters and enhances tumorigenesis.
AB  - Insulin-like growth factor 2 (IGF2), a developmentally regulated and maternally
      imprinted gene, is frequently overexpressed in pediatric cancers. Although loss
      of imprinting (LOI) at fetal promoters contributes to increased IGF2 in tumors,
      the magnitude of IGF2 expression suggests the involvement of additional
      regulatory mechanisms. A microRNA (miRNA) screen of primary Wilms' tumors
      identified specific overexpression of miR-483-5p, which is embedded within the
      IGF2 gene. Unexpectedly, the IGF2 mRNA itself is transcriptionally up-regulated
      by miR-483-5p. A nuclear pool of miR-483-5p binds directly to the 5' untranslated
      region (UTR) of fetal IGF2 mRNA, enhancing the association of the RNA helicase
      DHX9 to the IGF2 transcript and promoting IGF2 transcription. Ectopic expression
      of miR-483-5p in IGF2-dependent sarcoma cells is correlated with increased
      tumorigenesis in vivo. Together, these observations suggest a functional positive
      feedback loop of an intronic miRNA on transcription of its host gene.

PMID- 24298055
TI  - Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.
AB  - Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial
      function of Mediator in transcription is now largely established. However, we
      found that this complex also plays an important role by connecting transcription
      with DNA repair. We identified a functional contact between the Med17 Mediator
      subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA
      repair. Genome-wide location analyses revealed that Rad2 is associated with RNA
      polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in
      the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed
      genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene
      promoters is well correlated with that of Mediator. Furthermore, UV sensitivity
      of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and
      concomitant decrease of Mediator interaction with Rad2 protein. Our results
      suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment
      to transcribed genes.

PMID- 24298056
TI  - VHL-mediated disruption of Sox9 activity compromises beta-cell identity and
      results in diabetes mellitus.
AB  - Precise functioning of the pancreatic beta cell is paramount to whole-body
      glucose homeostasis, and beta-cell dysfunction contributes significantly to
      diabetes mellitus. Using transgenic mouse models, we demonstrate that deletion of
      the von Hippel-Lindau (Vhlh) gene (encoding an E3 ubiquitin ligase implicated in,
      among other functions, oxygen sensing in pancreatic beta cells) is deleterious to
      canonical beta-cell gene expression. This triggers erroneous expression of
      factors normally active in progenitor cells, including effectors of the Notch,
      Wnt, and Hedgehog signaling cascades. Significantly, an up-regulation of the
      transcription factor Sox9, normally excluded from functional beta cells, occurs
      upon deletion of Vhlh. Sox9 plays important roles during pancreas development but
      does not have a described role in the adult beta cell. beta-Cell-specific ectopic
      expression of Sox9 results in diabetes mellitus from similar perturbations in
      beta-cell identity. These findings reveal that assaults on the beta cell that
      impact the differentiation state of the cell have clear implications toward our
      understanding of diabetes mellitus.

PMID- 24298057
TI  - Ephrin-B2 controls PDGFRbeta internalization and signaling.
AB  - B-class ephrins, ligands for EphB receptor tyrosine kinases, are critical
      regulators of growth and patterning processes in many organs and species. In the
      endothelium of the developing vasculature, ephrin-B2 controls endothelial
      sprouting and proliferation, which has been linked to vascular endothelial growth
      factor (VEGF) receptor endocytosis and signaling. Ephrin-B2 also has essential
      roles in supporting mural cells (namely, pericytes and vascular smooth muscle
      cells [VSMCs]), but the underlying mechanism is not understood. Here, we show
      that ephrin-B2 controls platelet-derived growth factor receptor beta (PDGFRbeta)
      distribution in the VSMC plasma membrane, endocytosis, and signaling in a fashion
      that is highly distinct from its role in the endothelium. Absence of ephrin-B2 in
      cultured VSMCs led to the redistribution of PDGFRbeta from caveolin-positive to
      clathrin-associated membrane fractions, enhanced PDGF-B-induced PDGFRbeta
      internalization, and augmented downstream mitogen-activated protein (MAP) kinase
      and c-Jun N-terminal kinase (JNK) activation but impaired Tiam1-Rac1 signaling
      and proliferation. Accordingly, mutant mice lacking ephrin-B2 expression in
      vascular smooth muscle developed vessel wall defects and aortic aneurysms, which
      were associated with impaired Tiam1 expression and excessive activation of MAP
      kinase and JNK. Our results establish that ephrin-B2 is an important regulator of
      PDGFRbeta endocytosis and thereby acts as a molecular switch controlling the
      downstream signaling activity of this receptor in mural cells.

PMID- 24298058
TI  - MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and
      displacing its positive regulators.
AB  - The aquaglyceroprin Fps1 is responsible for glycerol transport in yeast in
      response to changes in extracellular osmolarity. Control of Fps1 channel activity
      in response to hyperosmotic shock involves a redundant pair of regulators, Rgc1
      (regulator of the glycerol channel 1) and Rgc2, and the MAPK Hog1 (high
      osmolarity glycerol response 1). However, the mechanism by which these factors
      influence channel activity is unknown. We show that Rgc2 maintains Fps1 in the
      open channel state in the absence of osmotic stress by binding to its C-terminal
      cytoplasmic domain. This interaction involves a tripartite pleckstrin homology
      (PH) domain within Rgc2 and a partial PH domain within Fps1. Activation of Hog1
      in response to hyperosmotic shock induces the rapid eviction of Rgc2 from Fps1
      and consequent channel closure. Hog1 was recruited to the N-terminal cytoplasmic
      domain of Fps1, which it uses as a platform from which to multiply phosphorylate
      Rgc2. Thus, these results reveal the mechanism by which Hog1 regulates Fps1 in
      response to hyperosmotic shock.

PMID- 24298059
TI  - Repurposing CRISPR/Cas9 for in situ functional assays.
AB  - RNAi combined with next-generation sequencing has proven to be a powerful and
      cost-effective genetic screening platform in mammalian cells. Still, this
      technology has its limitations and is incompatible with in situ mutagenesis
      screens on a genome-wide scale. Using p53 as a proof-of-principle target, we
      readapted the CRISPR (clustered regularly interspaced short palindromic
      repeats)/Cas9 (CRISPR associated 9) genome-editing system to demonstrate the
      feasibility of this methodology for targeted gene disruption positive selection
      assays. By using novel "all-in-one" lentiviral and retroviral delivery vectors
      heterologously expressing both a codon-optimized Cas9 and its synthetic guide RNA
      (sgRNA), we show robust selection for the CRISPR-modified Trp53 locus following
      drug treatment. Furthermore, by linking Cas9 expression to GFP fluorescence, we
      use an "all-in-one" system to track disrupted Trp53 in chemoresistant lymphomas
      in the EMU-myc mouse model. Deep sequencing analysis of the tumor-derived
      endogenous Cas9-modified Trp53 locus revealed a wide spectrum of mutants that
      were enriched with seemingly limited off-target effects. Taken together, these
      results establish Cas9 genome editing as a powerful and practical approach for
      positive in situ genetic screens.

PMID- 24298060
TI  - The sister chromatid cohesion pathway suppresses multiple chromosome gain and
      chromosome amplification.
AB  - Gain or loss of chromosomes resulting in aneuploidy can be important factors in
      cancer and adaptive evolution. Although chromosome gain is a frequent event in
      eukaryotes, there is limited information on its genetic control. Here we measured
      the rates of chromosome gain in wild-type yeast and sister chromatid cohesion
      (SCC) compromised strains. SCC tethers the newly replicated chromatids until
      anaphase via the cohesin complex. Chromosome gain was measured by selecting and
      characterizing copper-resistant colonies that emerged due to increased copies of
      the metallothionein gene CUP1. Although all defective SCC diploid strains
      exhibited increased rates of chromosome gain, there were 15-fold differences
      between them. Of all mutants examined, a hypomorphic mutation at the cohesin
      complex caused the highest rate of chromosome gain while disruption of WPL1, an
      important regulator of SCC and chromosome condensation, resulted in the smallest
      increase in chromosome gain. In addition to defects in SCC, yeast cell type
      contributed significantly to chromosome gain, with the greatest rates observed
      for homozygous mating-type diploids, followed by heterozygous mating type, and
      smallest in haploids. In fact, wpl1-deficient haploids did not show any
      difference in chromosome gain rates compared to wild-type haploids. Genomic
      analysis of copper-resistant colonies revealed that the "driver" chromosome for
      which selection was applied could be amplified to over five copies per diploid
      cell. In addition, an increase in the expected driver chromosome was often
      accompanied by a gain of a small number of other chromosomes. We suggest that
      while chromosome gain due to SCC malfunction can have negative effects through
      gene imbalance, it could also facilitate opportunities for adaptive changes. In
      multicellular organisms, both factors could lead to somatic diseases including
      cancer. 

PMID- 24298062
TI  - Speed of invasion of an expanding population by a horizontally transmitted trait.
AB  - Range expansions are a ubiquitous phenomenon, leading to the spatial spread of
      genetic, ecological, and cultural traits. While some of these traits are
      advantageous (and hence selected), other, nonselected traits can also spread by
      hitchhiking on the wave of population expansion. This requires us to understand
      how the spread of a hitchhiking trait is coupled to the wave of advance of its
      host population. Here, we use a system of coupled Fisher-Kolmogorov-Petrovsky
      Piskunov (F-KPP) equations to describe the spread of a horizontally transmitted
      hitchhiking trait within a population as it expands. We extend F-KPP wave theory
      to the system of coupled equations to predict how the hitchhiking trait spreads
      as a wave within the expanding population. We show that the speed of this trait
      wave is controlled by an intricate coupling between the tip of the population and
      trait waves. Our analysis yields a new speed selection mechanism for coupled
      waves of advance and reveals the existence of previously unexpected speed
      transitions. 

PMID- 24298061
TI  - Additive, epistatic, and environmental effects through the lens of expression
      variability QTL in a twin cohort.
AB  - The expression of a gene can vary across individuals in the general population,
      as well as between monozygotic twins. This variable expression is assumed to be
      due to the influence of both genetic and nongenetic factors. Yet little evidence
      supporting this assumption has been obtained from empirical data. In this study,
      we used expression data from a large twin cohort to investigate the influences of
      genetic and nongenetic factors on variable gene expression. We focused on a set
      of expression variability QTL (evQTL)--i.e., genetic loci associated with the
      variance, as opposed to the mean, of gene expression. We identified evQTL for 99,
      56, and 79 genes in lymphoblastoid cell lines, skin, and fat, respectively. The
      differences in gene expression, measured by the relative mean difference (RMD),
      tended to be larger between pairs of dizygotic (DZ) twins than between pairs of
      monozygotic (MZ) twins, showing that genetic background influenced the expression
      variability. Furthermore, a more profound RMD was observed between pairs of MZ
      twins whose genotypes were associated with greater expression variability than
      the RMD found between pairs of MZ twins whose genotypes were associated with
      smaller expression variability. This suggests that nongenetic (e.g.,
      environmental) factors contribute to the variable expression. Lastly, we
      demonstrated that the formation of evQTL is likely due to partial linkages
      between eQTL SNPs that are additively associated with the mean of gene
      expression; in most cases, no epistatic effect is involved. Our findings have
      implications for understanding divergent sources of gene expression variability.

PMID- 24298064
TI  - On masterpieces and breast cancer research.

PMID- 24298065
TI  - Progress in breast cancer: overview.
AB  - This edition of CCR Focus titled Research in Breast Cancer: Frontiers in
      Genomics, Biology, and Clinical Investigation reviews six topics that cover areas
      of translational research of high impact in breast cancer. These topics represent
      areas of breast cancer research where significant progress has occurred but also
      where very important challenges remain. The papers in this CCR Focus section are
      contributed by experts in the respective areas of investigation. Herein, key
      aspects of these contributions and the research directions they propose are
      reviewed.

PMID- 24298066
TI  - Neoadjuvant therapy as a platform for drug development and approval in breast
      cancer.
AB  - The traditional drug development process in breast cancer based on large phase
      III studies has serious limitations and needs a major overhaul. Searching for new
      approaches, the testing of novel agents in the preoperative (neoadjuvant) setting
      approach offers a potentially rapid and efficient strategy for drug development
      utilizing pathologic complete response (path CR), a surrogate marker for
      survival, as the primary endpoint. In addition, neoadjuvant studies allow the
      assessment of drug effects on the target (pharmacodynamic response) and the
      development of predictive biomarkers of response. Molecular profiling of the
      residual tumor in the surgical specimen may also provide insights into actionable
      mechanisms of resistance. Recognizing the potential of neoadjuvant trials for
      drug development, the U.S. Food and Drug Administration (FDA) recently announced
      consideration of neoadjuvant trials for accelerated drug approval in early breast
      cancer, particularly for tumors with high risk of recurrence and unfavorable
      prognosis, and provided accelerated approval to neoadjuvant pertuzumab in
      September 2013. The FDA has emphasized that while improvement in path CR could be
      utilized for "accelerated" approval, improvement in survival will still need to
      be demonstrated for "regular" approval. Key considerations in conduct of such
      neoadjuvant drug development trials include (i) study design such as utilization
      of biomarker stratified design to evaluate a biomarker that could enrich
      response, (ii) definition of path CR, (iii) distribution of factors that
      influence path CR between the treatment arms, (iv) prespecified plan for follow
      up to obtain data on survival, and (v) safety as it involves a patient population
      with curable disease. In the years to come, we anticipate an increase in the
      number of neoadjuvant trials testing novel therapies that hopefully will open a
      new path in bringing efficacious new therapies to patients with breast cancer.

PMID- 24298067
TI  - Incorporating genomics into breast cancer clinical trials and care.
AB  - Advances in DNA sequencing provide the potential for clinical assays that are
      timely and affordable and use small amounts of clinical material. The hypothesis
      has therefore been raised that marked improvements in patient outcomes will
      result when DNA diagnostics are matched to an armamentarium of targeted agents.
      While this may be partially true, much of the novel biology uncovered by recent
      sequencing analysis is poorly understood and not druggable with existing agents.
      Significant other challenges remain before these technologies can be successfully
      implemented in the clinic, including the predictive accuracy of pathway-based
      models, distinguishing drivers from passenger mutations, development of rational
      combinations, addressing genomic heterogeneity, and molecular
      evolution/resistance mechanisms. Developments in regulatory science will also
      need to proceed in parallel to scientific advances so that targeted treatment
      approaches can be delivered to small subsets of patients with defined biology and
      drug reimbursement is available for individuals whose tumor carries a mutation
      that has been successfully targeted in another malignancy, as long as they agree
      to participate in an outcome registry.

PMID- 24298068
TI  - Tackling the diversity of triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) comprises a highly diverse collection of
      cancers. Here, we review this diversity both in terms of gene expression subtypes
      and the repertoire of genetic events. Transcriptomic analyses of TNBC have
      revealed at least six subtypes, with the luminal androgen receptor (luminal AR)
      or molecular apocrine cancers forming a distinct group within triple-negative
      disease. Distinct from the gene expression subtypes, a diverse set of genetic
      events have been described in TNBC, with a number of potentially targetable
      genetic events found although all at relatively low frequency. Clinical trials to
      define the clinical utility of therapies targeting these low-frequency events
      will require substantial screening efforts to identify sufficient patients. Set
      against the diversity of TNBC, clinical studies of patients with triple-negative
      disease will need to be either focused on molecularly defined subsets with
      upfront molecular stratification, or powered for a secondary endpoint analysis of
      a molecularly defined subset. Such approaches will be crucial to realize the
      potential of precision medicine for patients with TNBCs.

PMID- 24298069
TI  - Metastasis dormancy in estrogen receptor-positive breast cancer.
AB  - About 20% to 40% of patients with breast cancer eventually develop recurrences in
      distant organs, which are often not detected until years to decades after the
      primary tumor diagnosis. This phenomenon is especially pronounced in estrogen
      receptor-positive (ER(+)) breast cancer, suggesting that ER(+) cancer cells may
      stay dormant for a protracted period of time, despite adjuvant therapies.
      Multiple mechanisms have been proposed to explain how cancer cells survive and
      remain in dormancy, and how they become reactivated and exit dormancy. These
      mechanisms include angiogenic switch, immunosurveillance, and interaction with
      extracellular matrix and stromal cells. How to eradicate or suppress these
      dormant cancer cells remains a major clinical issue because of the lack of
      knowledge about the biologic and clinical nature of these cells. Herein, we
      review the clinical manifestation of metastasis dormancy in ER(+) tumors, the
      current biologic insights regarding tumor dormancy obtained from various
      experimental models, and the clinical challenges to predict, detect, and treat
      dormant metastases. We also discuss future research directions toward a better
      understanding of the biologic mechanisms and clinical management of ER(+) dormant
      metastasis.

PMID- 24298070
TI  - Can immunity to breast cancer eliminate residual micrometastases?
AB  - An effective immune response has the potential for breast cancer sterilization
      with marked reduction in the potential for disease relapse. Adaptive type I
      immune cells uniquely have the capability of (i) cytotoxic T-cell activation and
      proliferation until all antigen expressing cells are eradicated, (ii) traversing
      endothelial barriers to penetrate tumor deposits wherever they occur, and (iii)
      immunologic memory, which allows the persistence of destructive immunity over the
      years it may take for breast cancer micrometastases to become clinically evident.
      Numerous recent investigations suggest that some breast cancers stimulate the
      type of immunity that results in a decreased risk of relapse. Moreover, the
      endogenous type I tumor microenvironment or type I immunity induced by drugs or
      biologic agents may improve response to standard therapies, further lowering the
      probability of disease recurrence.

PMID- 24298071
TI  - CNS metastases in breast cancer: old challenge, new frontiers.
AB  - Despite major therapeutic advances in the management of patients with breast
      cancer, central nervous system (CNS) metastases remain an intractable problem,
      particularly in patients with metastatic HER2-positive and triple-negative breast
      cancer. As systemic therapies to treat extracranial disease improve, some
      patients are surviving longer, and the frequency of CNS involvement seems to be
      increasing. Furthermore, in the early-stage setting, the CNS remains a potential
      sanctuary site for relapse. This review highlights advances in the development of
      biologically relevant preclinical models, including the development of brain
      tropic cell lines for testing of agents to prevent and treat brain metastases,
      and summarizes our current understanding of the biology of CNS relapse. From a
      clinical perspective, a variety of therapeutic approaches are discussed,
      including methods to improve drug delivery, novel cytotoxic agents, and targeted
      therapies. Challenges in current trial design and endpoints are reviewed.
      Finally, we discuss promising new directions, including novel trial designs,
      correlative imaging techniques, and enhanced translational opportunities.

PMID- 24298072
TI  - The omics of triple-negative breast cancers.
AB  - BACKGROUND: Triple-negative breast cancers (TNBC) do not represent a single
      disease subgroup and are often aggressive breast cancers with poor prognoses.
      Unlike estrogen/progesterone receptor and HER2 (human epidermal growth factor
      receptor 2) breast cancers, which are responsive to targeted treatments, there is
      no effective targeted therapy for TNBC, although approximately 50% of patients
      respond to conventional chemotherapies, including taxanes, anthracyclines,
      cyclophosphamide, and platinum salts. CONTENT: Genomic studies have helped
      clarify some of the possible disease groupings that make up TNBC. We discuss the
      findings, including copy number-transcriptome analysis, whole genome sequencing,
      and exome sequencing, in terms of the biological properties and phenotypes that
      make up the constellation of TNBC. The relationships between subgroups defined by
      transcriptome and genome analysis are discussed. SUMMARY: TNBC is not a uniform
      molecular or disease entity but a constellation of variably well-defined
      biological properties whose relationship to each other is not understood. There
      is good support for the existence of a basal expression subtype, p53 mutated,
      high-genomic instability subtype of TNBC. This should be considered a distinct
      TNBC subtype. Other subtypes with variable degrees of supporting evidence exist
      within the nonbasal/p53wt (wild-type p53) TNBC, including a group of TNBC with
      PI3K (phosphoinositide 3-kinase) pathway activation that have better overall
      prognosis than the basal TNBC. Consistent molecular phenotyping of TNBC by whole
      genome sequencing, transcriptomics, and functional studies with patient-derived
      tumor xenograft models will be essential components in clinical and biological
      studies as means of resolving this heterogeneity.

PMID- 24298074
TI  - Using growth curves to forecast regional resource recovery: approaches, analytics
      and consistency tests.
AB  - There is growing concern about the depletion of hydrocarbon resources and the
      risk of near-term peaks in production. These concerns hinge upon contested
      estimates of the recoverable resources of different regions and the associated
      forecasts of regional production. Beginning with Hubbert, an influential group of
      analysts have used growth curves both to estimate recoverable resources and to
      forecast future production. Despite widespread use, these 'curve-fitting'
      techniques remain a focus of misunderstanding and dispute. The aim of this paper
      is to classify and explain these techniques and to identify both their relative
      suitability in different circumstances and the expected level of confidence in
      their results. The paper develops a mathematical framework that maps curve
      fitting techniques onto the available data for conventional oil and highlights
      the critical importance of the so-called 'reserve growth'. It then summarizes the
      historical origins, contemporary application and strengths and weaknesses of each
      group of curve-fitting techniques and uses illustrative data from a number of oil
      producing regions to explore the extent to which these techniques provide
      consistent estimates of recoverable resources. The paper argues that the
      applicability of curve-fitting techniques is more limited than adherents claim,
      the confidence bounds on the results are wider than commonly assumed and the
      techniques have a tendency to underestimate recoverable resources. 

PMID- 24298075
TI  - Hydrocarbon liquefaction: viability as a peak oil mitigation strategy.
AB  - Current world capacity of hydrocarbon liquefaction is around 400,000 barrels per
      day, providing a marginal share of the global liquid fuel supply. This study
      performs a broad review of technical, economic, environmental and supply chain
      issues related to coal-to-liquids (CTL) and gas-to-liquids (GTL). We find three
      issues predominate. First, significant amounts of coal and gas would be required
      to obtain anything more than a marginal production of liquids. Second, the
      economics of CTL plants are clearly prohibitive, but are better for GTL.
      Nevertheless, large-scale GTL plants still require very high upfront costs, and
      for three real-world GTL plants out of four, the final cost has been so far
      approximately three times that initially budgeted. Small-scale GTL holds
      potential for associated gas. Third, both CTL and GTL incur significant
      environmental impacts, ranging from increased greenhouse gas emissions (in the
      case of CTL) to water contamination. Environmental concerns may significantly
      affect growth of these projects until adequate solutions are found.

PMID- 24298073
TI  - Independent RNA polymerase II preinitiation complex dynamics and nucleosome
      turnover at promoter sites in vivo.
AB  - Transcription by all three eukaryotic RNA polymerases involves the assembly of a
      large preinitiation complex (PIC) at gene promoters. The PIC comprises several
      general transcription factors (GTFs), including TBP, and the respective RNA
      polymerase. It has been suggested that some GTFs remain stably bound at active
      promoters to facilitate multiple transcription events. Here we used two
      complementary approaches to show that, in G1-arrested yeast cells, TBP exchanges
      very rapidly even at the most highly active RNA Pol II promoters. A similar
      situation is observed at RNA Pol III promoters. In contrast, TBP remains stably
      bound at RNA Pol I promoters. We also provide evidence that, unexpectedly, PIC
      dynamics are neither the cause nor the consequence of nucleosome exchange at most
      of the RNA Pol II promoters we analyzed. These results point to a stable
      reinitiation complex at RNA Pol I promoters and suggest independent PIC and
      nucleosome turnover at many RNA Pol II promoters. 

PMID- 24298076
TI  - Recovery rates, enhanced oil recovery and technological limits.
AB  - Enhanced oil recovery (EOR) techniques can significantly extend global oil
      reserves once oil prices are high enough to make these techniques economic. Given
      a broad consensus that we have entered a period of supply constraints, operators
      can at last plan on the assumption that the oil price is likely to remain
      relatively high. This, coupled with the realization that new giant fields are
      becoming increasingly difficult to find, is creating the conditions for extensive
      deployment of EOR. This paper provides a comprehensive overview of the nature,
      status and prospects for EOR technologies. It explains why the average oil
      recovery factor worldwide is only between 20% and 40%, describes the factors that
      contribute to these low recoveries and indicates which of those factors EOR
      techniques can affect. The paper then summarizes the breadth of EOR processes,
      the history of their application and their current status. It introduces two new
      EOR technologies that are beginning to be deployed and which look set to enter
      mainstream application. Examples of existing EOR projects in the mature oil
      province of the North Sea are discussed. It concludes by summarizing the future
      opportunities for the development and deployment of EOR. 

PMID- 24298077
TI  - Biofuels in the long-run global energy supply mix for transportation.
AB  - Various policy instruments along with increasing oil prices have contributed to a
      sixfold increase in global biofuels production over the last decade (2000-2010).
      This rapid growth has proved controversial, however, and has raised concerns over
      potential conflicts with global food security and climate change mitigation. To
      address these concerns, policy support is now focused on advanced or second
      generation biofuels instead of crop-based first-generation biofuels. This policy
      shift, together with the global financial crisis, has slowed the growth of
      biofuels production, which has remained stagnant since 2010. Based upon a review
      of the literature, this paper examines the potential long-run contribution of
      biofuels to the global energy mix, particularly for transportation. We find that
      the contribution of biofuels to global transportation fuel demand is likely to be
      limited to around 5% over the next 10-15 years. However, a number of studies
      suggest that biofuels could contribute up to a quarter of global transportation
      fuel demand by 2050, provided technological breakthroughs reduce the costs of
      sustainably produced advanced biofuels to a level where they can compete with
      petroleum fuels. 

PMID- 24298078
TI  - The future of oil: unconventional fossil fuels.
AB  - Unconventional fossil hydrocarbons fall into two categories: resource plays and
      conversion-sourced hydrocarbons. Resource plays involve the production of
      accumulations of solid, liquid or gaseous hydro-carbons that have been generated
      over geological time from organic matter in source rocks. The character of these
      hydrocarbons may have been modified subsequently, especially in the case of
      solids and extra-heavy liquids. These unconventional hydrocarbons therefore
      comprise accumulations of hydrocarbons that are trapped in an unconventional
      manner and/or whose economic exploitation requires complex and technically
      advanced production methods. This review focuses primarily on unconventional
      liquid hydro-carbons. The future potential of unconventional gas, especially
      shale gas, is also discussed, as it is revolutionizing the energy outlook in
      North America and elsewhere. 

PMID- 24298079
TI  - An assessment of electric vehicles: technology, infrastructure requirements,
      greenhouse-gas emissions, petroleum use, material use, lifetime cost, consumer
      acceptance and policy initiatives.
AB  - Concerns about climate change, urban air pollution and dependence on unstable and
      expensive supplies of foreign oil have led policy-makers and researchers to
      investigate alternatives to conventional petroleum-fuelled internal-combustion
      engine vehicles in transportation. Because vehicles that get some or all of their
      power from an electric drivetrain can have low or even zero emissions of
      greenhouse gases (GHGs) and urban air pollutants, and can consume little or no
      petroleum, there is considerable interest in developing and evaluating advanced
      electric vehicles (EVs), including pure battery-electric vehicles, plug-in hybrid
      electric vehicles and hydrogen fuel-cell electric vehicles. To help researchers
      and policy-makers assess the potential of EVs to mitigate climate change and
      reduce petroleum use, this paper discusses the technology of EVs, the
      infrastructure needed for their development, impacts on emissions of GHGs,
      petroleum use, materials use, lifetime costs, consumer acceptance and policy
      considerations. 

PMID- 24298080
TI  - Market-driven considerations affecting the prospects of alternative road fuels.
AB  - Without significant intervention, demand for crude oil could rise by a further
      25% by 2035, stemming from its use for transportation, particularly road
      transport. Many technologies for alternative fuels and substitute transport
      energy carriers are being researched, but successful implementation of these
      technologies at scale will require attention to consumer-behavioural and policy
      challenges as well as adapting existing or introducing new commercial value
      chains. In particular, there will be new capital-intensive roles for which there
      are no obvious contenders as yet. The legacy of diverse urban planning and fuel
      taxation policies and varying degrees of consumer inertia will lead to different
      rates of adoption of different alternative technologies in regional markets. In
      the absence of technology that provides a compelling consumer proposition,
      substitution of crude demand in mature markets will be challenging, as will be
      channelling exponential growth from growing markets like China into less crude
      intensive road transport solutions. 

PMID- 24298081
TI  - Oil and the world economy: some possible futures.
AB  - This paper, using a six-region dynamic stochastic general equilibrium model of
      the world economy, assesses the output and current account implications of
      permanent oil supply shocks hitting the world economy. For modest-sized shocks
      and conventional production technologies, the effects are modest. But for larger
      shocks, for elasticities of substitution that decline as oil usage is reduced to
      a minimum, and for production functions in which oil acts as a critical enabler
      of technologies, output growth could drop significantly. Also, oil prices could
      become so high that smooth adjustment, as assumed in the model, may become very
      difficult. 

PMID- 24298082
TI  - Decline and depletion rates of oil production: a comprehensive investigation.
AB  - Two of the most fundamental concepts in the current debate about future oil
      supply are oilfield decline rates and depletion rates. These concepts are
      related, but not identical. This paper clarifies the definitions of these
      concepts, summarizes the underlying theory and empirically estimates decline and
      depletion rates for different categories of oilfield. A database of 880 post-peak
      fields is analysed to determine typical depletion levels, depletion rates and
      decline rates. This demonstrates that the size of oilfields has a significant
      influence on decline and depletion rates, with generally high values for small
      fields and comparatively low values for larger fields. These empirical findings
      have important implications for oil supply forecasting. 

PMID- 24298083
TI  - Exploring the undulating plateau: the future of global oil supply.
AB  - In this paper, we analyse the factors that will influence long-term oil supply
      and describe the future form of the global oil supply profile as an 'undulating
      plateau' rather than an irreversible, short-term peak or an ever upward trend of
      increasing production. The ultimate transition from a world of relatively
      plentiful and cheap oil to one of tight supply and high cost will be slow and
      challenging. An understanding of the signposts for the future path of supply and
      the drivers of that profile will be critical to managing the transition. The
      ultimate form of the global supply curve may well be dictated by demand evolution
      rather than a limited resource endowment in the longer term. Several factors will
      probably control future global oil supply. We believe that the scale of global
      oil resource will not constitute a physical supply limit for at least the next
      two or three decades. However, all categories of oil resources are already more
      expensive to develop than in the past, requiring high oil prices to stimulate
      supply growth. Lower rates of oil demand growth relative to economic growth,
      combined with more challenging supply growth, will probably lead to an undulating
      plateau sometime after 2040, with demand from non-Organization for Economic
      Cooperation and Development states continuing to dominate. Upstream investment
      requirements and oil price volatility will increase towards and beyond the
      undulating production plateau. In this new world, high oil prices will induce
      demand destruction, fuel substitution and ever increasing energy efficiency. As
      we discuss below, the fundamental differences between the IHS Cambridge Energy
      Research Associates' (IHS CERA) view of the future of oil supply and many peak
      oil supply models are the timing of the onset of a dramatic slowdown in the rate
      of growth of supply and the existence or otherwise of a production plateau. We do
      not dispute that supply will plateau and eventually fall; the question is when,
      how and at what price? As the plateau approaches, oil prices are likely to
      increase strongly, with some very severe spikes along the way. 

PMID- 24298084
TI  - The implications of the declining energy return on investment of oil production.
AB  - Declining production from conventional oil resources has initiated a global
      transition to unconventional oil, such as tar sands. Unconventional oil is
      generally harder to extract than conventional oil and is expected to have a
      (much) lower energy return on (energy) investment (EROI). Recently, there has
      been a surge in publications estimating the EROI of a number of different sources
      of oil, and others relating EROI to long-term economic growth, profitability and
      oil prices. The following points seem clear from a review of the literature: (i)
      the EROI of global oil production is roughly 17 and declining, while that for the
      USA is 11 and declining; (ii) the EROI of ultra-deep-water oil and oil sands is
      below 10; (iii) the relation between the EROI and the price of oil is inverse and
      exponential; (iv) as EROI declines below 10, a point is reached when the relation
      between EROI and price becomes highly nonlinear; and (v) the minimum oil price
      needed to increase the oil supply in the near term is at levels consistent with
      levels that have induced past economic recessions. From these points, I conclude
      that, as the EROI of the average barrel of oil declines, long-term economic
      growth will become harder to achieve and come at an increasingly higher
      financial, energetic and environmental cost. 

PMID- 24298085
TI  - The future of oil supply.
AB  - Abundant supplies of oil form the foundation of modern industrial economies, but
      the capacity to maintain and grow global supply is attracting increasing concern.
      Some commentators forecast a peak in the near future and a subsequent terminal
      decline in global oil production, while others highlight the recent growth in
      'tight oil' production and the scope for developing unconventional resources.
      There are disagreements over the size, cost and recoverability of different
      resources, the technical and economic potential of different technologies, the
      contribution of different factors to market trends and the economic implications
      of reduced supply. Few debates are more important, more contentious, more wide
      ranging or more confused. This paper summarizes the main concepts, terms, issues
      and evidence that are necessary to understand the 'peak oil' debate. These
      include: the origin, nature and classification of oil resources; the trends in
      oil production and discoveries; the typical production profiles of oil fields,
      basins and producing regions; the mechanisms underlying those profiles; the
      extent of depletion of conventional oil; the risk of an approaching peak in
      global production; and the potential of various mitigation options. The aim is to
      introduce the subject to non-specialist readers and provide a basis for the
      subsequent papers in this Theme Issue. 

PMID- 24298086
TI  - Preface. The future of oil supply.

PMID- 24298087
TI  - Editorial 2014.

PMID- 24298092
TI  - Violence and abuse.

PMID- 24298093
TI  - Future directions for NICE.

PMID- 24298094
TI  - Improving the quality of care for medical inpatients by placing a higher priority
      on ward rounds.
AB  - Models suggested for managing acute, non-elective, medical admissions include
      expanding geriatric services, extending the role of the acute physician and
      rejuvenating the role of the general physician. We investigated improving
      inpatient care by changing consultants' work patterns and placing a higher
      priority on the ward rounds. A focus group and a questionnaire were used to study
      the impact on several ward round parameters. All respondents reported an overall
      satisfaction: 93% rated the quality of care as good or excellent, 75% reported
      increased safe patient discharges and 68% observed improved teamwork. Length of
      stay reduced to 4 days from 5.3 days without an increase in readmission. The main
      themes showed improved quality of care, better assured patients and relatives,
      and better consultant job satisfaction, but also showed reduced junior doctors'
      independent decision-making and a slight reduction in specialty-related activity.
      The study concluded that placing a higher priority on ward rounds by altering
      consultants' work patterns has a positive impact on inpatient care. 

PMID- 24298095
TI  - Developing a strategy for accreditation of clinical services.
AB  - Accreditation is one method of assuring quality. Accreditation requires the
      setting of standards and the creation of a robust and reliable process for
      assessing them. Accreditation offers different advantages to different groups, eg
      quality assurance to commissioners and the boards of provider organisations,
      confidence and choice for patients, and a quality improvement pathway for
      services to follow. This paper is focused on service accreditation and it
      proposes that service accreditation be professionally led. 

PMID- 24298096
TI  - Percentage prevalence of patient and visitor violence against staff in high-risk
      UK medical wards.
AB  - Patient and visitor violence adversely affects staff and organisations; however,
      there are few UK data about patient and visitor violence on medical wards.
      Therefore, we conducted a cross-sectional study using a validated tool (Survey of
      Violence Experienced by Staff) in six medical wards in three North Wales district
      general hospitals to assess the prevalence of violence against healthcare staff.
      A total of 158 staff responded (12 men, 144 women, two not stated). We found
      that, within the previous 4 weeks, 83% of staff had experienced verbal
      aggression, 50% had been threatened and 63% had been physically assaulted. Of
      those assaulted, 56% sustained an injury, with three requiring medical assessment
      or treatment. Length of experience in the workplace correlated negatively with
      verbal abuse, but not with threats or assaults. Direct patient contact positively
      correlated with more overall incidents. There was no correlation between training
      in aggression management and the experience of incidents. Healthcare support
      workers and nurses reported a higher prevalence of patient and visitor violence
      compared with other groups of health worker. 

PMID- 24298097
TI  - Kisspeptin is providing new insights into the control of reproduction.
AB  - The kisspeptins are a group of recently discovered peptide hormones (collectively
      termed kisspeptin), which play a pivotal role in reproduction. Research
      investigating the actions of kisspeptin is helping to elucidate the regulatory
      mechanisms which govern fertility and may lead to the development of novel
      treatments for some reproductive disorders.

PMID- 24298098
TI  - The spinal cord-injured patient in the medical ward.
AB  - People with spinal cord injury (SCI) suffer from the complications of paralysis
      in addition to the diseases of the general population. Spinal injury centres in
      the UK are tasked primarily with looking after newly injured patients and
      patients with established SCI must often turn to their local hospitals and
      general physicians for inpatient medical care. This paper outlines investigation
      and management of some of the common conditions which the physician on the
      general ward might expect to come across in patients with SCI and also how best
      to maintain the general health of the SCI patient in hospital. 

PMID- 24298099
TI  - The quality of patient experience of short-stay acute medical admissions:
      findings of the Adult Inpatient Survey in England.
AB  - Introduction of the specialty of acute medicine and of acute medical units (AMUs)
      in the UK have been associated with improvements in mortality, length of stay and
      flow, but there is no literature on the patient experience during the early phase
      of acute medical admissions. We analysed the Adult Inpatient Survey (AIPS)
      findings for short-stay unscheduled medical admissions who did not move from
      their first admission ward (n=3325) and therefore are likely to have been managed
      entirely in the AMU. We compared these with short-stay emergencies in other
      specialties (n=3420) and short-stay scheduled admissions (n=10,347). Scheduled
      admissions reported a better experience for all survey items. Scores for
      unscheduled admissions were worse in medical patients compared with other
      specialties for pain control, privacy, involvement, information, and for a number
      of questions relating to information on discharge. The specialty of acute
      medicine should work to improve future patient experience. 

PMID- 24298100
TI  - Proximal colon cancer and serrated adenomas - hunting the missing 10%.
AB  - There is a 10% shortfall in the number of proximal colorectal cancer cases
      detected by the UK Bowel Cancer Screening Programme and the actual number of UK
      registered proximal colorectal cancers. Sessile serrated adenomas/polyps (SSA/P)
      are common premalignant lesions in the proximal colon and are notoriously
      difficult to spot endoscopically. Missed or dismissed SSA/Ps might contribute to
      this UK proximal colon cancer detection disparity. In Oxfordshire, a service
      evaluation audit and histological review has shown a linear increase in the
      detection rate of these lesions over the past 4 years. This is the result of
      increased endoscopist and pathologist awareness of these lesions and improved
      interdisciplinary communication. This is the result of increased endoscopist and
      pathologist awareness of these lesions, together with improved interdisciplinary
      communication, and we predict that this will lead to a comparable detection
      increase nationwide. Ongoing surveillance of an increasing number of these
      premalignant lesions could become a significant endoscopic resource requirement
      once UK guidelines on serrated lesion follow up are established. 

PMID- 24298101
TI  - Effectiveness of a geriatrician in the emergency department in facilitating safe
      admission prevention of older patients.
AB  - The decision to admit a frail older patient is rarely made by a geriatrician and
      often falls to staff in the emergency department (ED), who may not have the
      training to balance the risks, benefits and alternatives. We based a consultant
      geriatrician in the ED with the primary aim of facilitating admission prevention
      for older patients and this was achieved for 64% (543/848) of patients. A
      secondary aim was to facilitate direct admission to elderly care wards when
      admission was necessary, and this was achieved for 57% of admitted patients
      (174/305). The geriatrician was able to facilitate discharge from the ED for over
      half of potential 30-day readmissions seen. The overall 7-day ED re-attendance
      rate was 10.1%, but only 3.4% of patients were admitted with the same problem,
      indicating true admission prevention rather than admission delay. In conclusion,
      the placement of a consultant geriatrician in the ED is effective in facilitating
      admission prevention for older patients. 

PMID- 24298102
TI  - The impact of a new acute oncology service in acute hospitals: experience from
      the Clatterbridge Cancer Centre and Merseyside and Cheshire Cancer Network.
AB  - The 2008 National Confidential Enquiry into Patient Outcomes and Death
      highlighted an urgent need to improve the quality, safety and efficiency of care
      for cancer patients following emergency presentation to acute general hospitals.
      A network-wide acute oncology service (AOS) was therefore commissioned and
      implemented on the basis of recommendations from the National Chemotherapy
      Advisory Group (NCAG). Through a continuous programme of raising awareness
      regarding both the role of the AOS and the necessity of early patient referral to
      acute oncology teams, we have been able to establish an AOS across all acute
      trusts in our cancer network. The network-wide AOS has improved communication
      across clinical teams, enabled rapid review of over 3,000 patients by oncology
      staff, reduced hospital stay, increased understanding of oncology emergencies and
      their treatment, and enhanced pathways for rapid diagnosis and appropriate
      referrals for patients presenting with malignancy of undefined origin (MUO).
      These achievements have been made by developing a network protocol book for
      managing common oncology emergencies, by introducing local pathways for managing
      MUO and by collaborating with palliative care teams to introduce local acute
      oncology (AO) multi-disciplinary team (MDT) meetings. 

PMID- 24298103
TI  - Revalidation for trainees and the annual review of competency progression (ARCP).
AB  - Revalidation for doctors in the UK began in December 2012. Doctors in training
      need to revalidate every 5 years after obtaining their licence to practice and
      also at the point of achieving their certificate of completion of training. The
      annual review of competency progression (ARCP) is the vehicle for revalidation
      discussions. Postgraduate deans are the responsible officers for trainees and
      there are new processes in place, including responsibilities for educational
      supervisors and ARCP panels to ensure that postgraduate deans can fulfil their
      General Medical Council obligations. In this article, I give examples of how this
      might work in practice. 

PMID- 24298104
TI  - Funding of medical education: the need for transparency.
AB  - Medical education is vital to the future of healthcare provision. It is also
      expensive. We should ensure that the funding spent on medical education is spent
      in the most cost-effective way possible and delivers the best possible returns on
      our investment. Budgets that have been allocated to medical education should be
      spent on this and not on research or clinical care. Educational budgets should be
      transparent - so that their use and misuse are clear. We should develop a culture
      of lifelong learning and continually make explicit that future healthcare
      professionals need investment in their education to maintain the quality and
      safety of healthcare delivery. 

PMID- 24298105
TI  - Low vitamin D levels are associated with increased risk for fatty liver disease
      among non-obese adults.
AB  - Recent data have revealed an inverse relationship between insulin resistance,
      which is associated with fatty liver disease, and blood 25-hydroxy-vitamin D
      (25(OH)D) levels. The aim of the present study was to determine the association
      of vitamin D levels with the presence and stage of fatty liver disease among non
      obese subjects and to determine the effect of vitamin D status on fatty liver
      disease development. A total of 613 non-obese (body mass index <30 kg/m(2))
      gastroenterology and internal medicine outpatients (472 women and 141 men) were
      enrolled in the study. The patients' laboratory values, including liver function
      tests, lipid profiles, C-reactive protein, fasting blood glucose, insulin,
      calcium and 25(OH)D levels were studied. Low vitamin D levels, higher
      triglyceride levels and higher alanine aminotransferase levels were found to be
      the significant determinants for non-alcoholic fatty liver disease. When the
      patients were evaluated as low or normal vitamin D groups, low vitamin D levels
      was determined to be a risk factor for fatty liver disease, with an odds ratio of
      -1.59 (confidence interval -1.22 to -1.97). The increased risk for fatty liver
      disease among patients with low vitamin D status may be suggestive of mechanisms
      promoting fat flow and accumulation in the liver. Molecular studies are warranted
      to elucidate the action of vitamin D on the liver with respect to fat metabolism.

PMID- 24298106
TI  - Connective tissue disease in pregnancy.
AB  - Connective tissue diseases (CTD) include a variety of chronic multisystem
      disorders with a high percentage of autoimmune conditions. Many of these
      conditions affect women of childbearing age and, therefore, pregnancy poses an
      important challenge for doctors looking after such women. Knowledge of medication
      safety, the effect of pregnancy on such diseases and vice versa, together with
      preconception counselling and multidisciplinary team care, are the basic pillars
      needed to provide the best obstetric and medical care to these women. In this
      review, we discuss the management of the most common autoimmune CTD before,
      during and after pregnancy, along with the most relevant issues regarding
      appropriate medication. 

PMID- 24298107
TI  - Drug therapies in liver disease.
AB  - The likelihood of a general physician encountering a patient with compensated and
      decompensated liver disease is increasing. This article provides an overview of
      pharmaceutical agents currently used in the management of cirrhosis and is
      designed to allow a better understanding of the rationale for using certain drugs
      in patients with often complex pathology. 

PMID- 24298108
TI  - A case of collapse.
AB  - We describe the case of a woman who presented with seemingly non-specific
      symptoms, including collapse, but through examination was eventually revealed to
      have an unusual, potentially fatal, but treatable neurological condition. We
      share some thoughts on the process of diagnosis, the difficulty of diagnosing a
      rare disease and the practice of neurology on the acute medical take. We also
      highlight the value of screening neurological examination in acute medical
      patients. 

PMID- 24298109
TI  - The era of genomic medicine.
AB  - It is becoming increasingly clear that genomics is beginning to have a major
      impact in guiding diagnoses and treatment of many disorders. As the cost of DNA
      sequencing continues to drop and more patient genomes are sequenced, the
      challenge is to deliver this knowledge to the clinic, particularly in cancer. DNA
      sequencing of patients with rare disease is revealing novel druggable pathways
      for more common disorders. Genetic tools for treating disease are also advancing
      rapidly. Genetic approaches, thought to be pipedreams five years ago for diseases
      such as Duchenne muscular dystrophy, are now showing promise in clinical trials
      and many of these methodologies are being applied more widely for other diseases.
      The era of genomic medicine has arrived. 

PMID- 24298110
TI  - Acute coronary syndrome: optimising management through risk assessment.

PMID- 24298111
TI  - Atrial fibrillation: relieving symptoms and managing risk.

PMID- 24298112
TI  - The management of end-stage heart failure and reducing the risk of cardiorenal
      syndrome.

PMID- 24298113
TI  - Sudden cardiac death: detecting the warning signs.

PMID- 24298114
TI  - Lipid management: maximising reduction of cardiac risk.

PMID- 24298116
TI  - A case of refractory Ogilvie syndrome following a haemorrhagic stroke.

PMID- 24298117
TI  - A woman with progressive lethargy and sudden onset of shortness of breath.

PMID- 24298118
TI  - Intrathoracic chest wall lipoma: mimicking a soft tissue neoplasm on a chest
      radiograph.

PMID- 24298120
TI  - Patient's best interests and presumed consent in ante-mortem organ preservation
      in end-of-life care.

PMID- 24298121
TI  - Response.

PMID- 24298122
TI  - The impact of consultant-delivered multidisciplinary inpatient medical care on
      patient outcomes.

PMID- 24298123
TI  - A trainee's guide to surviving ePortfolio.

PMID- 24298124
TI  - 'Management of a tuberculosis exposure in the immunocompromised setting - are the
      NICE guidelines adequate?'.

PMID- 24298125
TI  - A cross-sectional audit of the uptake of the seasonal influenza vaccination by
      medical staff at a London hospital.

PMID- 24298127
TI  - Genetic and genomic literacy in pediatric primary care.
AB  - A colloquium on genetic literacy in pediatric primary care sponsored by the
      Health Resources and Services Administration Maternal and Child Health Bureau was
      held at the American Academy of Pediatrics headquarters on October 2-3, 2012. The
      overarching goal of the colloquium was to provide context for delivery of
      genetics-related services in day-to-day pediatric primary care practice,
      encompassing 3 dimensions of medicine: prevention, diagnosis, and management.
      Participants considered the whole spectrum of disease, from rare disorders to
      common disorders, the genetics-related components of which are often overlooked.
      Specific topics included family history, genomics, genetic literacy and
      competency, epigenetics, and a focused view of primary care and genetics. A
      consensus statement was developed to provide recommendations for integration of
      genetics into pediatric primary care. 

PMID- 24298128
TI  - Family history in primary care pediatrics.
AB  - The family history has been called the first genetic test; it was a core element
      of primary care long before the current wave of genetics technologies and
      services became clinically relevant. Risk assessment based on family history
      allows providers to personalize and prioritize health messages, shifts the focus
      of health care from treatment to prevention, and can empower individuals and
      families to be stewards of their own health. In a world of rising health care
      costs, the family history is an important tool, with its primary cost being the
      clinician's time. However, a recent National Institutes of Health conference
      highlighted the lack of substantive evidence to support the clinical utility of
      family histories. Annual collection of a comprehensive 3-generation family
      history has been held up as the gold standard for practice. However, interval
      family histories targeted to symptoms and family histories tailored to a child's
      life stage (ie, age-based health) may be important and underappreciated methods
      of collecting family history that yield clinically actionable data and supplement
      existing family history information. In this article, we review the various
      applications, as well as capabilities and limitations, of the family history for
      primary care providers. 

PMID- 24298129
TI  - Whole-exome/genome sequencing and genomics.
AB  - As medical genetics has progressed from a descriptive entity to one focused on
      the functional relationship between genes and clinical disorders, emphasis has
      been placed on genomics. Genomics, a subelement of genetics, is the study of the
      genome, the sum total of all the genes of an organism. The human genome, which is
      contained in the 23 pairs of nuclear chromosomes and in the mitochondrial DNA of
      each cell, comprises >6 billion nucleotides of genetic code. There are some
      23,000 protein-coding genes, a surprisingly small fraction of the total genetic
      material, with the remainder composed of noncoding DNA, regulatory sequences, and
      introns. The Human Genome Project, launched in 1990, produced a draft of the
      genome in 2001 and then a finished sequence in 2003, on the 50th anniversary of
      the initial publication of Watson and Crick's paper on the double-helical
      structure of DNA. Since then, this mass of genetic information has been
      translated at an ever-increasing pace into useable knowledge applicable to
      clinical medicine. The recent advent of massively parallel DNA sequencing (also
      known as shotgun, high-throughput, and next-generation sequencing) has brought
      whole-genome analysis into the clinic for the first time, and most of the current
      applications are directed at children with congenital conditions that are
      undiagnosable by using standard genetic tests for single-gene disorders. Thus,
      pediatricians must become familiar with this technology, what it can and cannot
      offer, and its technical and ethical challenges. Here, we address the concepts of
      human genomic analysis and its clinical applicability for primary care providers.

PMID- 24298130
TI  - Epigenetics and primary care.
AB  - Epigenetics, the study of functionally relevant chemical modifications to DNA
      that do not involve a change in the DNA nucleotide sequence, is at the interface
      between research and clinical medicine. Research on epigenetic marks, which
      regulate gene expression independently of the underlying genetic code, has
      dramatically changed our understanding of the interplay between genes and the
      environment. This interplay alters human biology and developmental trajectories,
      and can lead to programmed human disease years after the environmental exposure.
      In addition, epigenetic marks are potentially heritable. In this article, we
      discuss the underlying concepts of epigenetics and address its current and
      potential applicability for primary care providers. 

PMID- 24298131
TI  - Genetic literacy and competency.
AB  - Since the sequencing of the human genome was completed, progress toward
      understanding the genetic contributions to both rare and common disorders has
      accelerated dramatically. That understanding will lead to new approaches to
      diagnosis and management, which will be incorporated into day-to-day medical
      practice. Moreover, the mindset with regard to genetic contributions to health
      and disease has shifted from 1 gene at a time to genome wide. However, most
      practicing pediatricians, and even many still in training, are likely to be
      unfamiliar with the concepts of genetics and genomics and their applications in
      medical practice. This article addresses the issues of genetic and genomic
      literacy and competencies for pediatricians and other primary care providers, as
      they prepare to work with their patients in the emerging world of genomic
      medicine. 

PMID- 24298132
TI  - Primary care and genetics and genomics.
AB  - With the recent expansion of genetic science, its evolving translation to
      clinical medicine, and the growing number of available resources for genomics in
      primary care, the primary care provider must increasingly integrate genetics and
      genomics into daily practice. Because primary care medicine combines the
      treatment of acute illness with disease prevention and anticipatory guidance, the
      primary care provider is in an ideal position to evaluate and treat patients for
      genetic disease. The notion that genetic knowledge is only rarely needed will
      have to be replaced with a comprehensive approach that integrates "genetic
      thinking" into every patient encounter. Genomic competencies will need to be
      added to the primary care provider's repertoire; such competencies include
      prevention, assessment, evaluation, and diagnosis of genetic conditions; the
      ordering and interpreting of genetic tests; communication with families;
      appropriate referrals; and the management or comanagement of care. The process of
      deciding when to order genetic tests, what tests to order, and how to interpret
      the results is complex, and the tests and their results have specific risks and
      benefits, especially for pediatric patients. The longitudinal nature of primary
      pediatric care provides the opportunity to obtain and continually update the
      family history, which is the most powerful initial genetic "test." The ongoing
      provider-family relationship, coupled with the astounding number of advances in
      genetic and genomic testing, also necessitates a constant re-evaluation of past
      diagnosis or nondiagnosis. 

PMID- 24298133
TI  - Synaptic plasticity in health and disease: introduction and overview.
AB  - We summarize the reviews and research papers submitted by speakers at a
      discussion meeting on Synaptic Plasticity in Health and Disease held at the Royal
      Society, London on 2-3 December 2013, and a subsequent satellite meeting convened
      at the Royal Society/Kavli Centre at Chicheley Hall on 4-5 December 2013.
      Together, these contributions give an overview of current research and
      controversies in a vibrant branch of neuroscience with important implications for
      the understanding of many forms of learning and memory, and a wide spectrum of
      neurological and cognitive disorders. 

PMID- 24298134
TI  - NMDA receptor-dependent long-term potentiation comprises a family of temporally
      overlapping forms of synaptic plasticity that are induced by different patterns
      of stimulation.
AB  - N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is
      extensively studied since it is believed to use the same molecular mechanisms
      that are required for many forms of learning and memory. Unfortunately, many
      controversies exist, not least the seemingly simple issue concerning the locus of
      expression of LTP. Here, we review our recent work and some of the extensive
      literature on this topic and present new data that collectively suggest that LTP
      can be explained, during its first few hours, by the coexistence of at least
      three mechanistically distinct processes that are all triggered by the synaptic
      activation of NMDARs. 

PMID- 24298135
TI  - Spike-timing-dependent BDNF secretion and synaptic plasticity.
AB  - In acute hippocampal slices, we found that the presence of extracellular brain
      derived neurotrophic factor (BDNF) is essential for the induction of spike-timing
      dependent long-term potentiation (tLTP). To determine whether BDNF could be
      secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used
      a reduced system of dissociated hippocampal neurons in culture. Repetitive
      pairing of iontophoretically applied glutamate pulses at the dendrite with
      neuronal spikes could induce persistent alterations of glutamate-induced
      responses at the same dendritic site in a manner that mimics spike-timing
      dependent plasticity (STDP)-the glutamate-induced responses were potentiated and
      depressed when the glutamate pulses were applied 20 ms before and after neuronal
      spiking, respectively. By monitoring changes in the green fluorescent protein
      (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged
      BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal
      spiking resulted in BDNF secretion from the dendrite at the iontophoretic site
      only when the glutamate pulses were applied within a time window of approximately
      40 ms prior to neuronal spiking, consistent with the timing requirement of
      synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF
      secretion could be triggered in a spike-timing-dependent manner from the
      postsynaptic dendrite. 

PMID- 24298136
TI  - Long-term potentiation in hippocampal oriens interneurons: postsynaptic
      induction, presynaptic expression and evaluation of candidate retrograde factors.
AB  - Several types of hippocampal interneurons exhibit a form of long-term
      potentiation (LTP) that depends on Ca(2+)-permeable AMPA receptors and group I
      metabotropic glutamate receptors. Several sources of evidence point to a
      presynaptic locus of LTP maintenance. The retrograde factor that triggers the
      expression of LTP remains unidentified. Here, we show that trains of action
      potentials in putative oriens-lacunosum-moleculare interneurons of the mouse CA1
      region can induce long-lasting potentiation of stimulus-evoked excitatory
      postsynaptic currents that mimics LTP elicited by high-frequency afferent
      stimulation. We further report that blockers of nitric oxide production or TRPV1
      receptors failed to prevent LTP induction. The present results add to the
      evidence that retrograde signalling underlies N-methyl-d-aspartate (NMDA)
      receptor-independent LTP in oriens interneurons, mediated by an unidentified
      factor. 

PMID- 24298137
TI  - PSD-95 promotes the stabilization of young synaptic contacts.
AB  - Maintaining a population of stable synaptic connections is probably of critical
      importance for the preservation of memories and functional circuitry, but the
      molecular dynamics that underlie synapse stabilization is poorly understood.
      Here, we use simultaneous time-lapse imaging of post synaptic density-95 (PSD-95)
      and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to investigate the
      dynamics of protein composition at axodendritic (AD) contacts. Our data reveal
      that this composition is highly dynamic, with both proteins moving into and out
      of the same synapse independently, so that synapses cycle rapidly between states
      in which they are enriched for none, one or both proteins. We assessed how PSD-95
      and CaMKII interact at stable and transient AD sites and found that both phospho
      CaMKII and PSD-95 are present more often at stable than labile contacts. Finally,
      we found that synaptic contacts are more stable in older neurons, and this
      process can be mimicked in younger neurons by overexpression of PSD-95. Taken
      together, these data show that synaptic protein composition is highly variable
      over a time-scale of hours, and that PSD-95 is probably a key synaptic protein
      that promotes synapse stability. 

PMID- 24298138
TI  - The expression of long-term potentiation: reconciling the preists and the
      postivists.
AB  - Long-term potentiation (LTP) of excitatory synaptic transmission in the
      hippocampus has been investigated in great detail over the past 40 years. Where
      and how LTP is actually expressed, however, remain controversial issues.
      Considerable evidence has been offered to support both pre- and postsynaptic
      contributions to LTP expression. Though it is widely held that postsynaptic
      expression mechanisms are the primary contributors to LTP expression, evidence
      for that conclusion is amenable to alternative explanations. Here, we briefly
      review some key contributions to the 'locus' debate and describe data that
      support a dominant role for presynaptic mechanisms. Recognition of the state
      dependency of expression mechanisms, and consideration of the consequences of the
      spatial relationship between postsynaptic glutamate receptors and presynaptic
      vesicular release sites, lead to a model that may reconcile views from both sides
      of the synapse. 

PMID- 24298139
TI  - Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10
      years on.
AB  - This review focuses on the research that has occurred over the past decade which
      has solidified a postsynaptic expression mechanism for long-term potentiation
      (LTP). However, experiments that have suggested a presynaptic component are also
      summarized. It is argued that the pairing of glutamate uncaging onto single
      spines with postsynaptic depolarization provides the final and most elegant
      demonstration of a postsynaptic expression mechanism for NMDA receptor-dependent
      LTP. The fact that the magnitude of this LTP is similar to that evoked by pairing
      synaptic stimulation and depolarization leaves little room for a substantial
      presynaptic component. Finally, recent data also require a revision in our
      thinking about the way AMPA receptors (AMPARs) are recruited to the postsynaptic
      density during LTP. This recruitment is independent of subunit type, but does
      require an adequate reserve pool of extrasynaptic receptors. 

PMID- 24298140
TI  - Alternative polyadenylation and differential expression of Shank mRNAs in the
      synaptic neuropil.
AB  - The stability and dynamics of synapses rely on tight regulation of the synaptic
      proteome. Shank proteins, encoded by the three genes Shank1, Shank2 and Shank3
      are scaffold molecules in the postsynaptic density of excitatory neurons that
      contribute to activity-dependent neuronal signalling. Mutations in the Shank
      genes are associated with neurological diseases. Using state-of-the-art
      technologies, we investigated the levels of expression of the Shank family
      messenger RNAs (mRNAs) within the synaptic neuropil of the rat hippocampus. We
      detected all three Shank transcripts in the neuropil of CA1 pyramidal neurons. We
      found Shank1 to be the most abundantly expressed among the three Shank mRNA
      homologues. We also examined the turnover of Shank mRNAs and predict the half
      lives of Shank1, Shank2 and Shank3 mRNAs to be 18-28 h. Using 3'-end sequencing,
      we identified novel 3' ends for the Shank1 and Shank2 3' untranslated regions (3'
      UTRs) that may contribute to the diversity of alternative polyadenylation (APA)
      for the Shank transcripts. Our findings consolidate the view that the Shank
      molecules play a central role at the postsynaptic density. This study may shed
      light on synaptopathologies associated with disruption of local protein
      synthesis, perhaps linked to mutations in mRNA 3' UTRs or inappropriate 3' end
      processing. 

PMID- 24298141
TI  - Long-term depression: a cell biological view.
AB  - Recent studies of the molecular mechanisms of long-term depression (LTD) suggest
      a crucial role for the signalling pathways of apoptosis (programmed cell death)
      in the weakening and elimination of synapses and dendritic spines. With this
      backdrop, we suggest that LTD can be considered as the electrophysiological
      aspect of a larger cell biological programme of synapse involution, which uses
      localized apoptotic mechanisms to sculpt synapses and circuits without causing
      cell death. 

PMID- 24298142
TI  - Cellular and subcellular localization of PKMzeta.
AB  - In contrast to protein kinases that participate in long-term potentiation (LTP)
      induction and memory consolidation, the autonomously active atypical protein
      kinase C isoform, protein kinase Mzeta (PKMzeta), functions in the core molecular
      mechanism of LTP maintenance and long-term memory storage. Here, using multiple
      complementary techniques for light and electron microscopic immunolocalization,
      we present the first detailed characterization of the cellular and subcellular
      distribution of PKMzeta in rat hippocampus and neocortex. We find that PKMzeta is
      widely expressed in forebrain with prominent immunostaining in hippocampal and
      neocortical grey matter, and weak label in white matter. In hippocampal and
      cortical pyramidal cells, PKMzeta expression is predominantly somatodendritic,
      and electron microscopy highlights the kinase at postsynaptic densities and in
      clusters within spines. In addition, nuclear label and striking punctate
      immunopositive structures in a paranuclear and dendritic distribution are seen by
      confocal microscopy, occasionally at dendritic bifurcations. PKMzeta
      immunoreactive granules are observed by electron microscopy in cell bodies and
      dendrites, including endoplasmic reticulum. The widespread distribution of
      PKMzeta in nuclei, nucleoli and endoplasmic reticulum suggests potential roles of
      this kinase in cell-wide mechanisms involving gene expression, biogenesis of
      ribosomes and new protein synthesis. The localization of PKMzeta within
      postsynaptic densities and spines suggests sites where the kinase stores
      information during LTP maintenance and long-term memory. 

PMID- 24298143
TI  - GluA2-dependent AMPA receptor endocytosis and the decay of early and late long
      term potentiation: possible mechanisms for forgetting of short- and long-term
      memories.
AB  - The molecular processes involved in establishing long-term potentiation (LTP)
      have been characterized well, but the decay of early and late LTP (E-LTP and L
      LTP) is poorly understood. We review recent advances in describing the mechanisms
      involved in maintaining LTP and homeostatic plasticity. We discuss how these
      phenomena could relate to processes that might underpin the loss of synaptic
      potentiation over time, and how they might contribute to the forgetting of short
      term and long-term memories. We propose that homeostatic downscaling mediates the
      loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP,
      while both processes require the activity-dependent removal of postsynaptic GluA2
      containing AMPA receptors. 

PMID- 24298144
TI  - Inception of a false memory by optogenetic manipulation of a hippocampal memory
      engram.
AB  - Memories can be easily distorted, and a lack of relevant animal models has
      largely hindered our understanding of false-memory formation. Here, we first
      identified a population of cells in the dentate gyrus (DG) of the hippocampus
      that bear the engrams for a specific context; these cells were naturally
      activated during the encoding phase of fear conditioning and their artificial
      reactivation using optogenetics in an unrelated context was sufficient for
      inducing the fear memory specific to the conditioned context. In a further study,
      DG or CA1 neurons activated by exposure to a particular context were labelled
      with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated
      during fear conditioning in a different context. The DG experimental group showed
      increased freezing in the original context in which a foot shock was never
      delivered. The recall of this false memory was context specific, activated
      similar downstream regions engaged during natural fear-memory recall, and was
      also capable of driving an active fear response. Together, our data demonstrate
      that by substituting a natural conditioned stimulus with optogenetically
      reactivated DG cells that bear contextual memory engrams, it is possible to
      incept an internally and behaviourally represented false fear memory. 

PMID- 24298145
TI  - Shank mutant mice as an animal model of autism.
AB  - In this review, we focus on the role of the Shank family of proteins in autism.
      In recent years, autism research has been flourishing. With genetic, molecular,
      imaging and electrophysiological studies being supported by behavioural studies
      using animal models, there is real hope that we may soon understand the
      fundamental pathology of autism. There is also genuine potential to develop a
      molecular-level pharmacological treatment that may be able to deal with the most
      severe symptoms of autism, and clinical trials are already underway. The Shank
      family of proteins has been strongly implicated as a contributing factor in
      autism in certain individuals and sits at the core of the alleged autistic
      pathway. Here, we analyse studies that relate Shank to autism and discuss what
      light this sheds on the possible causes of autism. 

PMID- 24298146
TI  - Microtubule-associated protein tau is essential for long-term depression in the
      hippocampus.
AB  - The microtubule-associated protein tau is a principal component of
      neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's
      disease and other tauopathies. However, it is unknown how a protein that is
      primarily located in axons is involved in a disease that is believed to have a
      synaptic origin. To investigate a possible synaptic function of tau, we studied
      synaptic plasticity in the hippocampus and found a selective deficit in long-term
      depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was
      replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD
      is associated with the glycogen synthase kinase-3-mediated phosphorylation of
      tau. These observations demonstrate that tau has a critical physiological
      function in LTD. 

PMID- 24298147
TI  - GluA1 trafficking and metabotropic NMDA: addressing results from other
      laboratories inconsistent with ours.
AB  - We have previously shown that when over-expressed in neurons, green fluorescent
      protein (GFP) tagged GluA1 (GluA1-GFP) delivery into synapses is dependent on
      plasticity. A recent study suggests that GluA1 over-expression leads to its
      incorporation into the synapse, in the absence of additional long-term
      potentiation-like manipulations. It is possible that a GFP tag was responsible
      for the difference. Using rectification index as a measure of synaptic delivery
      of GluA1, we found no difference in the synaptic delivery of GluA1-GFP versus
      untagged GluA1. We recently published a study showing that while D-APV blocks
      NMDAr-dependent long-term depression (LTD), MK-801 and 7-chloro kynurenate (7CK)
      fail to block LTD. We propose a metabotropic function for the NMDA receptor in
      LTD induction. In contrast to our observations, recent unpublished data suggest
      that the above antagonists are equally effective in blocking LTD. We noticed
      different methodology in their study. Here, we show that their methodology has
      complex effects on synaptic transmission. Therefore, it is not possible to
      conclude that 7CK is effective in blocking LTD from their type of experiment. 

PMID- 24298148
TI  - Long-term potentiation in the anterior cingulate cortex and chronic pain.
AB  - Glutamate is the primary excitatory transmitter of sensory transmission and
      perception in the central nervous system. Painful or noxious stimuli from the
      periphery 'teach' humans and animals to avoid potentially dangerous objects or
      environments, whereas tissue injury itself causes unnecessary chronic pain that
      can even last for long periods of time. Conventional pain medicines often fail to
      control chronic pain. Recent neurobiological studies suggest that synaptic
      plasticity taking place in sensory pathways, from spinal dorsal horn to cortical
      areas, contributes to chronic pain. Injuries trigger long-term potentiation of
      synaptic transmission in the spinal cord dorsal horn and anterior cingulate
      cortex, and such persistent potentiation does not require continuous neuronal
      activity from the periphery. At the synaptic level, potentiation of excitatory
      transmission caused by injuries may be mediated by the enhancement of glutamate
      release from presynaptic terminals and potentiated postsynaptic responses of AMPA
      receptors. Preventing, 'erasing' or reducing such potentiation may serve as a new
      mechanism to inhibit chronic pain in patients in the future. 

PMID- 24298149
TI  - Neurotransmitter receptor and time dependence of the synaptic plasticity
      disrupting actions of Alzheimer's disease Abeta in vivo.
AB  - Many endogenous factors influence the time course and extent of the detrimental
      effects of amyloid beta-protein (Abeta) on synaptic function. Here, we assessed
      the impact of varying endogenous glutamatergic and cholinergic transmission by
      pharmacological means on the disruption of plasticity at hippocampal CA3-to-CA1
      synapses in the anaesthetized rat. NMDA receptors (NMDARs) are considered
      critical in mediating Abeta-induced inhibition of long-term potentiation (LTP).
      However, intracerebroventricular injection of Abeta1-42 inhibited not only NMDAR
      dependent LTP but also voltage-activated Ca(2+)-dependent LTP induced by strong
      conditioning stimulation during NMDAR blockade. On the other hand, another form
      of NMDAR-independent synaptic plasticity, endogenous acetylcholine-induced
      muscarinic receptor-dependent long-term enhancement, was not hindered by Abeta1
      42. Interestingly, augmenting endogenous acetylcholine activation of nicotinic
      receptors prior to the injection of Abeta1-42 prevented the inhibition of NMDAR
      dependent LTP, whereas the same intervention when introduced after the infusion
      of Abeta was ineffective. We also examined the duration of action of Abeta,
      including water soluble Abeta from Alzheimer's disease (AD) brain. Remarkably,
      the inhibition of LTP induction caused by a single injection of sodium dodecyl
      sulfate-stable Abeta dimer-containing AD brain extract persisted for at least a
      week. These findings highlight the need to increase our understanding of non
      NMDAR mechanisms and of developing novel means of overcoming, rather than just
      preventing, the deleterious synaptic actions of Abeta. 

PMID- 24298150
TI  - Mechanisms of heterosynaptic metaplasticity.
AB  - Synaptic plasticity is fundamental to the neural processes underlying learning
      and memory. Interestingly, synaptic plasticity itself can be dynamically
      regulated by prior activity, in a process termed 'metaplasticity', which can be
      expressed both homosynaptically and heterosynaptically. Here, we focus on
      heterosynaptic metaplasticity, particularly long-range interactions between
      synapses spread across dendritic compartments, and review evidence for
      intracellular versus intercellular signalling pathways leading to this effect. Of
      particular interest is our previously reported finding that priming stimulation
      in stratum oriens of area CA1 in the hippocampal slice heterosynaptically
      inhibits subsequent long-term potentiation and facilitates long-term depression
      in stratum radiatum. As we have excluded the most likely intracellular signalling
      pathways that might mediate this long-range heterosynaptic effect, we consider
      the hypothesis that intercellular communication may be critically involved. This
      hypothesis is supported by the finding that extracellular ATP hydrolysis, and
      activation of adenosine A2 receptors are required to induce the metaplastic
      state. Moreover, delivery of the priming stimulation in stratum oriens elicited
      astrocytic calcium responses in stratum radiatum. Both the astrocytic responses
      and the metaplasticity were blocked by gap junction inhibitors. Taken together,
      these findings support a novel intercellular communication system, possibly
      involving astrocytes, being required for this type of heterosynaptic
      metaplasticity. 

PMID- 24298151
TI  - Hippocampal NMDA receptors are important for behavioural inhibition but not for
      encoding associative spatial memories.
AB  - The idea that an NMDA receptor (NMDAR)-dependent long-term potentiation-like
      process in the hippocampus is the neural substrate for associative spatial
      learning and memory has proved to be extremely popular and influential. However,
      we recently reported that mice lacking NMDARs in dentate gyrus and CA1
      hippocampal subfields (GluN1(DeltaDGCA1) mice) acquired the open field, spatial
      reference memory watermaze task as well as controls, a result that directly
      challenges this view. Here, we show that GluN1(DeltaDGCA1) mice were not impaired
      during acquisition of a spatial discrimination watermaze task, during which mice
      had to choose between two visually identical beacons, based on extramaze spatial
      cues, when all trials started at locations equidistant between the two beacons.
      They were subsequently impaired on test trials starting from close to the decoy
      beacon, conducted post-acquisition. GluN1(DeltaDGCA1) mice were also impaired
      during reversal of this spatial discrimination. Thus, contrary to the widely held
      belief, hippocampal NMDARs are not required for encoding associative, long-term
      spatial memories. Instead, hippocampal NMDARs, particularly in CA1, act as part
      of a comparator system to detect and resolve conflicts arising when two
      competing, behavioural response options are evoked concurrently, through
      activation of a behavioural inhibition system. These results have important
      implications for current theories of hippocampal function. 

PMID- 24298152
TI  - Untangling the two-way signalling route from synapses to the nucleus, and from
      the nucleus back to the synapses.
AB  - During learning and memory, it has been suggested that the coordinated electrical
      activity of hippocampal neurons translates information about the external
      environment into internal neuronal representations, which then are stored
      initially within the hippocampus and subsequently into other areas of the brain.
      A widely held hypothesis posits that synaptic plasticity is a key feature that
      critically modulates the triggering and the maintenance of such representations,
      some of which are thought to persist over time as traces or tags. However, the
      molecular and cell biological basis for these traces and tags has remained
      elusive. Here, we review recent findings that help clarify some of the molecular
      and cellular mechanisms critical for these events, by untangling a two-way
      signalling crosstalk route between the synapses and the neuronal soma. In
      particular, a detailed interrogation of the soma-to-synapse delivery of immediate
      early gene product Arc/Arg3.1, whose induction is triggered by heightened
      synaptic activity in many brain areas, teases apart an unsuspected 'inverse'
      synaptic tagging mechanism that likely contributes to maintaining the contrast of
      synaptic weight between strengthened and weak synapses within an active ensemble.

PMID- 24298153
TI  - Stress enhances fear by forming new synapses with greater capacity for long-term
      potentiation in the amygdala.
AB  - Prolonged and severe stress leads to cognitive deficits, but facilitates
      emotional behaviour. Little is known about the synaptic basis for this contrast.
      Here, we report that in rats subjected to chronic immobilization stress, long
      term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are
      enhanced in principal neurons of the lateral amygdala, a brain area involved in
      fear memory formation. This is accompanied by electrophysiological and
      morphological changes consistent with the formation of 'silent synapses',
      containing only NMDARs. In parallel, chronic stress also reduces synaptic
      inhibition. Together, these synaptic changes would enable amygdalar neurons to
      undergo further experience-dependent modifications, leading to stronger fear
      memories. Consistent with this prediction, stressed animals exhibit enhanced
      conditioned fear. Hence, stress may leave its mark in the amygdala by generating
      new synapses with greater capacity for plasticity, thereby creating an ideal
      neuronal substrate for affective disorders. These findings also highlight the
      unique features of stress-induced plasticity in the amygdala that are strikingly
      different from the stress-induced impairment of structure and function in the
      hippocampus. 

PMID- 24298154
TI  - Functional MRI of long-term potentiation: imaging network plasticity.
AB  - Neurons are able to express long-lasting and activity-dependent modulations of
      their synapses. This plastic property supports memory and conveys an
      extraordinary adaptive value, because it allows an individual to learn from, and
      respond to, changes in the environment. Molecular and physiological changes at
      the cellular level as well as network interactions are required in order to
      encode a pattern of synaptic activity into a long-term memory. While the cellular
      mechanisms linking synaptic plasticity to memory have been intensively studied,
      those regulating network interactions have received less attention. Combining
      high-resolution fMRI and in vivo electrophysiology in rats, we have previously
      reported a functional remodelling of long-range hippocampal networks induced by
      long-term potentiation (LTP) of synaptic plasticity in the perforant pathway.
      Here, we present new results demonstrating an increased bilateral coupling in the
      hippocampus specifically supported by the mossy cell commissural/associational
      pathway in response to LTP. This fMRI-measured increase in bilateral connectivity
      is accompanied by potentiation of the corresponding polysynaptically evoked
      commissural potential in the contralateral dentate gyrus and depression of the
      inactive convergent commissural pathway to the ipsilateral dentate. We review
      these and previous findings in the broader context of memory consolidation. 

PMID- 24298155
TI  - Two sides to long-term potentiation: a view towards reconciliation.
AB  - Almost since the discovery of long-term potentiation (LTP) in the hippocampus,
      its locus of expression has been debated. Throughout the years, convincing
      evidence has accumulated to suggest that LTP can be supported either
      presynaptically, by an increase in transmitter release, or postsynaptically, by
      an increase in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptor number. However, whereas postsynaptic enhancement appears to be
      consistently obtained across studies following LTP induction, presynaptic
      enhancement is not as reliably observed. Such discrepancies, along with the
      failure to convincingly identify a retrograde messenger required for presynaptic
      change, have led to the general view that LTP is mainly supported
      postsynaptically, and certainly, research within the field for the past decade
      has been heavily focused on the postsynaptic locus. Here, we argue that LTP can
      be expressed at either synaptic locus, but that pre- and postsynaptic forms of
      LTP are dissociable phenomena mediated by distinct mechanistic processes, which
      are sensitive to different patterns of neuronal activity. This view of LTP helps
      to reconcile discrepancies across the literature and may put to rest a decades
      long debate. 

PMID- 24298156
TI  - Leptin regulation of hippocampal synaptic function in health and disease.
AB  - The endocrine hormone leptin plays a key role in regulating food intake and body
      weight via its actions in the hypothalamus. However, leptin receptors are highly
      expressed in many extra-hypothalamic brain regions and evidence is growing that
      leptin influences many central processes including cognition. Indeed, recent
      studies indicate that leptin is a potential cognitive enhancer as it markedly
      facilitates the cellular events underlying hippocampal-dependent learning and
      memory, including effects on glutamate receptor trafficking, neuronal morphology
      and activity-dependent synaptic plasticity. However, the ability of leptin to
      regulate hippocampal synaptic function markedly declines with age and aberrant
      leptin function has been linked to neurodegenerative disorders such as
      Alzheimer's disease (AD). Here, we review the evidence supporting a cognitive
      enhancing role for the hormone leptin and discuss the therapeutic potential of
      using leptin-based agents to treat AD. 

PMID- 24298157
TI  - Incorporation of inwardly rectifying AMPA receptors at silent synapses during
      hippocampal long-term potentiation.
AB  - Despite decades of study, the mechanisms by which synapses express the increase
      in strength during long-term potentiation (LTP) remain an area of intense
      interest. Here, we have studied how AMPA receptor subunit composition changes
      during the early phases of hippocampal LTP in CA1 pyramidal neurons. We studied
      LTP at silent synapses that initially lack AMPA receptors, but contain NMDA
      receptors. We show that strongly inwardly rectifying AMPA receptors are initially
      incorporated at silent synapses during LTP and are then subsequently replaced by
      non-rectifying AMPA receptors. These findings suggest that silent synapses
      initially incorporate GluA2-lacking, calcium-permeable AMPA receptors during LTP
      that are then replaced by GluA2-containing calcium-impermeable receptors. We also
      show that LTP consolidation at CA1 synapses requires a rise in intracellular
      calcium concentration during the early phase of expression, indicating that
      calcium influx through the GluA2-lacking AMPA receptors drives their replacement
      by GluA2-containing receptors during LTP consolidation. Taken together with
      previous studies in hippocampus and in other brain regions, these findings
      suggest that a common mechanism for the expression of activity-dependent
      glutamatergic synaptic plasticity involves the regulation of GluA2-subunit
      composition and highlights a critical role for silent synapses in this process. 

PMID- 24298158
TI  - Synaptic competition in structural plasticity and cognitive function.
AB  - Connections between neurons can undergo long-lasting changes in synaptic strength
      correlating with changes in structure. These events require the synthesis of new
      proteins, the availability of which can lead to cooperative and competitive
      interactions between synapses for the expression of plasticity. These processes
      can occur over limited spatial distances and temporal periods, defining dendritic
      regions over which activity may be integrated and could lead to the physical
      rewiring of synapses into functional groups. Such clustering of inputs may
      increase the computational power of neurons by allowing information to be
      combined in a greater than additive manner. The availability of new proteins may
      be a key modulatory step towards activity-dependent, long-term growth or
      elimination of spines necessary for remodelling of connections. Thus, the
      aberrant growth or shrinkage of dendritic spines could occur if protein levels
      are misregulated. Indeed, such perturbations can be seen in several mental
      retardation disorders, wherein either too much or too little protein translation
      exists, matching an observed increase or decrease in spine density, respectively.
      Cellular events which alter protein availability could relieve a constraint on
      synaptic competition and disturb synaptic clustering mechanisms. These changes
      may be detrimental to modifications in neural circuitry following activity. 

PMID- 24298160
TI  - Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long
      term spatial recognition memory.
AB  - It is well established that Zif268/Egr1, a member of the Egr family of
      transcription factors, is critical for the consolidation of several forms of
      memory; however, it is as yet uncertain whether increasing expression of Zif268
      in neurons can facilitate memory formation. Here, we used an inducible transgenic
      mouse model to specifically induce Zif268 overexpression in forebrain neurons and
      examined the effect on recognition memory and hippocampal synaptic transmission
      and plasticity. We found that Zif268 overexpression during the establishment of
      memory for objects did not change the ability to form a long-term memory of
      objects, but enhanced the capacity to form a long-term memory of the spatial
      location of objects. This enhancement was paralleled by increased long-term
      potentiation in the dentate gyrus of the hippocampus and by increased activity
      dependent expression of Zif268 and selected Zif268 target genes. These results
      provide novel evidence that transcriptional mechanisms engaging Zif268 contribute
      to determining the strength of newly encoded memories. 

PMID- 24298159
TI  - Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion
      molecule NGL-3 through NMDA receptors, matrix metalloproteinases and
      presenilin/gamma-secretase.
AB  - Long-term depression (LTD) reduces the functional strength of excitatory synapses
      through mechanisms that include the removal of AMPA glutamate receptors from the
      postsynaptic membrane. LTD induction is also known to result in structural
      changes at excitatory synapses, including the shrinkage of dendritic spines.
      Synaptic adhesion molecules are thought to contribute to the development,
      function and plasticity of neuronal synapses largely through their trans-synaptic
      adhesions. However, little is known about how synaptic adhesion molecules are
      altered during LTD. We report here that NGL-3 (netrin-G ligand-3), a postsynaptic
      adhesion molecule that trans-synaptically interacts with the LAR family of
      receptor tyrosine phosphatases and intracellularly with the postsynaptic
      scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3
      cleavage is induced by NMDA treatment in cultured neurons and low-frequency
      stimulation in brain slices and requires the activities of NMDA glutamate
      receptors, matrix metalloproteinases (MMPs) and presenilin/gamma-secretase. These
      results suggest that NGL-3 is a novel substrate of MMPs and gamma-secretase and
      that NGL-3 cleavage may regulate synaptic adhesion during LTD. 

PMID- 24298161
TI  - Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive
      disabilities through dysregulation of the cAMP/PKA signalling pathway.
AB  - Loss-of-function mutations in the gene encoding for the RhoGAP protein of
      oligophrenin-1 (OPHN1) lead to cognitive disabilities (CDs) in humans, yet the
      underlying mechanisms are not known. Here, we show that in mice constitutive lack
      of Ophn1 is associated with dysregulation of the cyclic adenosine
      monophosphate/phosphate kinase A (cAMP/PKA) signalling pathway in a brain-area
      specific manner. Consistent with a key role of cAMP/PKA signalling in regulating
      presynaptic function and plasticity, we found that PKA-dependent presynaptic
      plasticity was completely abolished in affected brain regions, including
      hippocampus and amygdala. At the behavioural level, lack of OPHN1 resulted in
      hippocampus- and amygdala-related learning disabilities which could be fully
      rescued by the ROCK/PKA kinase inhibitor fasudil. Together, our data identify
      OPHN1 as a key regulator of presynaptic function and suggest that, in addition to
      reported postsynaptic deficits, loss of presynaptic plasticity contributes to the
      pathophysiology of CDs. 

PMID- 24298162
TI  - The search for a hippocampal engram.
AB  - Understanding the molecular and cellular changes that underlie memory, the
      engram, requires the identification, isolation and manipulation of the neurons
      involved. This presents a major difficulty for complex forms of memory, for
      example hippocampus-dependent declarative memory, where the participating neurons
      are likely to be sparse, anatomically distributed and unique to each individual
      brain and learning event. In this paper, I discuss several new approaches to this
      problem. In vivo calcium imaging techniques provide a means of assessing the
      activity patterns of large numbers of neurons over long periods of time with
      precise anatomical identification. This provides important insight into how the
      brain represents complex information and how this is altered with learning. The
      development of techniques for the genetic modification of neural ensembles based
      on their natural, sensory-evoked, activity along with optogenetics allows direct
      tests of the coding function of these ensembles. These approaches provide a new
      methodological framework in which to examine the mechanisms of complex forms of
      learning at the level of the neurons involved in a specific memory. 

PMID- 24298163
TI  - Synaptic plasticity in multiple sclerosis and in experimental autoimmune
      encephalomyelitis.
AB  - Approximately half of all patients with multiple sclerosis (MS) experience
      cognitive dysfunction, including learning and memory impairment. Recent studies
      suggest that hippocampal pathology is involved, although the mechanisms
      underlying these deficits remain poorly understood. Evidence obtained from a
      mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests
      that in the hippocampus of EAE mice long-term potentiation (LTP) is favoured over
      long-term depression in response to repetitive synaptic activation, through a
      mechanism dependent on enhanced IL-1beta released from infiltrating lymphocytes
      or activated microglia. Facilitated LTP during an immune-mediated attack might
      underlie functional recovery, but also cognitive deficits and excitotoxic
      neurodegeneration. Having identified that pro-inflammatory cytokines such as IL
      1beta can influence synaptic function and integrity in early MS, it is hoped that
      new treatments targeted towards preventing synaptic pathology can be developed. 

PMID- 24298165
TI  - Moderate AMPA receptor clustering on the nanoscale can efficiently potentiate
      synaptic current.
AB  - The prevailing view at present is that postsynaptic expression of the classical
      NMDA receptor-dependent long-term potentiation relies on an increase in the
      numbers of local AMPA receptors (AMPARs). This is thought to parallel an
      expansion of postsynaptic cell specializations, for instance dendritic spine
      heads, which accommodate synaptic receptor proteins. However, glutamate released
      into the synaptic cleft can normally activate only a hotspot of low-affinity
      AMPARs that occur in the vicinity of the release site. How the enlargement of the
      AMPAR pool is causally related to the potentiated AMPAR current remains therefore
      poorly understood. To understand possible scenarios of postsynaptic potentiation,
      here we explore a detailed Monte Carlo model of the typical small excitatory
      synapse. Simulations suggest that approximately 50% increase in the synaptic
      AMPAR current could be provided by expanding the existing AMPAR pool at the
      expense of 100-200% new AMPARs added at the same packing density. Alternatively,
      reducing the inter-receptor distances by only 30-35% could achieve a similar
      level of current potentiation without any changes in the receptor numbers. The
      NMDA receptor current also appears sensitive to the NMDA receptor crowding. Our
      observations provide a quantitative framework for understanding the 'resource
      efficient' ways to enact use-dependent changes in the architecture of central
      synapses. 

PMID- 24298164
TI  - GluN2A and GluN2B subunit-containing NMDA receptors in hippocampal plasticity.
AB  - N-Methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity is a strong
      candidate to mediate learning and memory processes that require the hippocampus.
      This plasticity is bidirectional, and how the same receptor can mediate opposite
      changes in synaptic weights remains a conundrum. It has been suggested that the
      NMDAR subunit composition could be involved. Specifically, one subunit
      composition of NMDARs would be responsible for the induction of long-term
      potentiation (LTP), whereas NMDARs with a different subunit composition would be
      engaged in the induction of long-term depression (LTD). Unfortunately, the
      results from studies that have investigated this hypothesis are contradictory,
      particularly in relation to LTD. Nevertheless, current evidence does suggest that
      the GluN2B subunit might be particularly important for plasticity and may make a
      synapse bidirectionally malleable. In particular, we conclude that the presence
      of GluN2B subunit-containing NMDARs at the postsynaptic density might be a
      necessary, though not a sufficient, condition for the strengthening of individual
      synapses. This is owing to the interaction of GluN2B with calcium/calmodulin
      dependent protein kinase II (CaMKII) and is distinct from its contribution as an
      ion channel. 

PMID- 24298168
TI  - Editorial 2014.

PMID- 24298166
TI  - How the mechanisms of long-term synaptic potentiation and depression serve
      experience-dependent plasticity in primary visual cortex.
AB  - Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to
      exemplify his theories of how the brain stores information through long-lasting
      homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional
      'Hebbian' plasticity in the modification of vision through experience. First, we
      discuss the consequences of monocular deprivation (MD) in the mouse, which have
      been studied by many laboratories over many years, and the evidence that synaptic
      depression of excitatory input from the thalamus is a primary contributor to the
      loss of visual cortical responsiveness to stimuli viewed through the deprived
      eye. Second, we describe a less studied, but no less interesting form of
      plasticity in the visual cortex known as stimulus-selective response potentiation
      (SRP). SRP results in increases in the response of V1 to a visual stimulus
      through repeated viewing and bears all the hallmarks of perceptual learning. We
      describe evidence implicating an important role for potentiation of thalamo
      cortical synapses in SRP. In addition, we present new data indicating that there
      are some features of this form of plasticity that cannot be fully accounted for
      by such feed-forward Hebbian plasticity, suggesting contributions from intra
      cortical circuit components. 

PMID- 24298169
TI  - Measurements of neutron energy spectra from 7Li(p,n)7Be reaction with Bonner
      sphere spectrometer, Nested Neutron Spectrometer and ROSPEC.
AB  - Neutron spectrometry measurements were carried out at the McMaster Accelerator
      Laboratory (MAL), which is equipped with a 3-MV Van de Graaff-type accelerator.
      Protons were accelerated onto a thick natural lithium target inducing the
      (7)Li(p,n)(7)Be threshold reaction. Depending on the proton energy, slightly
      different poly-energetic neutron fields were produced. Neutron spectra were
      measured at two incident proton energies: 2.15 and 2.24 MeV, which produced poly
      energetic neutrons with maximum kinetic energies of 401 and 511 keV,
      respectively. Measurements were performed at a distance of 1.5 m from the target
      in the forward direction with three different instruments: Bonner sphere
      spectrometer, Nested Neutron Spectrometer and ROtational proton recoil
      SPECtrometer. 

PMID- 24298167
TI  - The synaptic plasticity and memory hypothesis: encoding, storage and persistence.
AB  - The synaptic plasticity and memory hypothesis asserts that activity-dependent
      synaptic plasticity is induced at appropriate synapses during memory formation
      and is both necessary and sufficient for the encoding and trace storage of the
      type of memory mediated by the brain area in which it is observed. Criteria for
      establishing the necessity and sufficiency of such plasticity in mediating trace
      storage have been identified and are here reviewed in relation to new work using
      some of the diverse techniques of contemporary neuroscience. Evidence derived
      using optical imaging, molecular-genetic and optogenetic techniques in
      conjunction with appropriate behavioural analyses continues to offer support for
      the idea that changing the strength of connections between neurons is one of the
      major mechanisms by which engrams are stored in the brain. 

PMID- 24298170
TI  - A comparison of the response of PADC neutron dosemeters in high-energy neutron
      fields.
AB  - Within the framework of the EURADOS Working Group 11, a comparison of passive
      neutron dosemeters in high-energy neutron fields was organised in 2011. The aim
      of the exercise was to evaluate the response of poly-allyl-glycol-carbonate
      neutron dosemeters from various European dosimetry laboratories to high-energy
      neutron fields. Irradiations were performed at the iThemba LABS facility in South
      Africa with neutrons having energies up to 66 and 100 MeV. 

PMID- 24298171
TI  - How music alters a kiss: superior temporal gyrus controls fusiform-amygdalar
      effective connectivity.
AB  - While watching movies, the brain integrates the visual information and the
      musical soundtrack into a coherent percept. Multisensory integration can lead to
      emotion elicitation on which soundtrack valences may have a modulatory impact.
      Here, dynamic kissing scenes from romantic comedies were presented to 22
      participants (13 females) during functional magnetic resonance imaging scanning.
      The kissing scenes were either accompanied by happy music, sad music or no music.
      Evidence from cross-modal studies motivated a predefined three-region network for
      multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala
      (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this
      network were investigated using dynamic causal models of effective connectivity.
      This revealed bilinear modulations by happy and sad music with suppression
      effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal
      modeling showed a suppressive gating effect of aSTG on fusiform-amygdalar
      connectivity. In conclusion, fusiform to amygdala coupling strength is modulated
      via feedback through aSTG as region for multisensory integration of emotional
      material. This mechanism was emotion-specific and more pronounced for sad music.
      Therefore, soundtrack valences may modulate emotion elicitation in movies by
      differentially changing preprocessed visual information to the amygdala. 

PMID- 24298174
TI  - Horizons in Medicine 25: advancing on all levels.

PMID- 24298173
TI  - Navigating to excellence: solutions driving exceptional results.

PMID- 24298172
TI  - Impaired rich club connectivity in unaffected siblings of schizophrenia patients.
AB  - Schizophrenia has been conceptualized as a disorder of brain connectivity. Recent
      studies suggest that brain connectivity may be disproportionally impaired among
      the so-called rich club. This small core of densely interconnected hub regions
      has been hypothesized to form an important infrastructure for global brain
      communication and integration of information across different systems of the
      brain. Given the heritable nature of the illness, we hypothesized that
      connectivity disturbances, including abnormal rich club connectivity, may be
      related to familial vulnerability for schizophrenia. To test this hypothesis,
      both schizophrenia patients and unaffected siblings of patients were
      investigated. Rich club organization was examined in networks derived from
      diffusion-weighted imaging in 40 schizophrenia patients, 54 unaffected siblings
      of patients, and 51 healthy control subjects. Connectivity between rich club hubs
      was differentially reduced across groups (P = .014), such that it was highest in
      controls, intermediate in siblings (7.9% reduced relative to controls), and
      lowest in patients (19.6% reduced compared to controls). Furthermore, in
      patients, lower levels of rich club connectivity were found to be related to
      longer duration of illness and worse overall functioning. Together, these
      findings suggest that impaired rich club connectivity is related to familial,
      possibly reflecting genetic, vulnerability for schizophrenia. Our findings
      support a central role for abnormal rich club organization in the etiology of
      schizophrenia. 

PMID- 24298175
TI  - Repair-associated inflammation in nonalcoholic fatty liver disease.
AB  - The mechanisms that drive non-alcoholic fatty liver disease (NAFLD) progression
      from simple steatosis to non-alcoholic steatohepatitis (NASH) and NASH-fibrosis
      and/or cirrhosis are complex. Recent studies suggest that the liver progenitor
      cell (ie liver stem cell) population expands during chronic liver injury, and is
      an essential component of the repair process. Hedgehog (Hh) is a developmental
      morphogen that has an important role in the adult tissue repair (and progenitor)
      response. Accumulating data in mice and human show that resurrection of the Hh
      pathway occurs during progressive NAFLD, and that activity of this pathway
      correlates with NASH-fibrosis stage. Importantly, Hh ligands secreted by dying
      (or stressed) hepatocytes, hepatic stellate cells (i.e. myofibroblasts),
      cholangiocytes and recruited immune cells can act on neighbouring cells to
      perpetuate the fibrogenic response. Intriguingly, Hh ligands can also stimulate
      cholangiocytes to secrete chemokines that recruit immune cell subsets (such as
      natural killer T cells), which could explain why fibrosis generally occurs in the
      context of chronic inflammation (i.e. fibrosis-associated inflammatory response).
      Finally, the administration of Hh inhibitors led to reduced fibrosis in a model
      of NASH. Future studies are needed to evaluate the utility of these inhibitors in
      other models of chronic liver disease. If successful, this could pave the way for
      the development of new therapy for patients with NASH, because Hh pathway
      inhibitors have now been licensed for use in patients with advanced basal cell
      carcinoma.

PMID- 24298176
TI  - Stroke thrombolysis: where are we and where are we going?
AB  - Stroke is an important cause of death and disability throughout the world. Most
      strokes are ischaemic, caused by thrombotic or embolic occlusion of blood
      vessels. The advent of thrombolysis for acute ischaemic stroke has revolutionised
      the treatment of acute stroke in the developed world. The benefit of thrombolysis
      in acute stroke is very time-dependent, with the greatest benefit achieved when
      administered within 90 minutes of ictus, but trials demonstrating some benefit up
      to 4.5, and possibly 6 hours. This has revolutionised stroke treatment, with
      redesign of clinical pathways to try to ensure patients with suspected stroke
      reach a hospital with a thrombolysis service as quickly as possible. Clinical
      stroke services need to ensure that all acute stroke patients can be scanned,
      treated and admitted to stroke units without delay. Future research needs to
      address the prevention and better management of complications, such as secondary
      intracerebral haemorrhage and angioedema. In addition, the evidence base for
      direct intra-arterial intervention such as thrombectomy needs to be established. 

PMID- 24298177
TI  - HIV and the brain: from AIDS to old age.
AB  - The field of HIV medicine has changed rapidly in the last two decades since
      effective and tolerable antiretroviral treatment became available. As a result,
      although classical opportunistic infections of the brain have become less common,
      clinicians need to be aware of a wider range of acute and chronic complications
      of HIV and its treatment. In this article, we summarise major opportunistic
      infections, immune reconstitution inflammatory syndrome, HIV-associated
      neurocognitive disorders, and cerebrovascular disease in HIV positive patients.
      We also emphasise the preventability and reversibility of most of the central
      nervous system complications of HIV, and hence the importance of early diagnosis
      of HIV and involvement of clinicians with special expertise in HIV medicine. 

PMID- 24298178
TI  - The microbiome in inflammatory bowel disease and beyond.
AB  - The diverse and complex community of microorganisms that has co-evolved with the
      human gut is vital to intestinal functioning, and disturbances in the microbiota
      and its relationship with the host immune system have been linked to inflammatory
      bowel diseases, including Crohn's disease and ulcerative colitis. This has
      suggested several treatment options, including antibiotics, probiotics and faecal
      transplantation. The human microbiome project has been established to enable
      comprehensive characterisation of the human microbiota and in the coming years,
      knowledge in this area is expected to continue to expand. 

PMID- 24298179
TI  - Emerging roles for cardiovascular magnetic resonance.
AB  - Cardiovascular magnetic resonance (CMR) is a noninvasive imaging tool with high
      spatial resolution in the absence of ionising radiation. CMR imaging is routine
      in the functional assessment of coronary lesions and is widely held as the gold
      standard in myocardial viability imaging. Its unique tissue characterisation
      capabilities have revolutionised the assessment of the cardiomyopathies and it is
      the investigation of choice for cardiovascular surveillance imaging. To date its
      greatest success has been in the management of thalassaemia major, where the
      ability to detect myocardial iron loading has significantly improved patient
      survival. In the near future, CMR fibrosis imaging may serve as a risk
      stratification tool for the cardiomyopathies; and the ability to assess
      interstitial fibrosis may advance this role into other disease processes. Novel
      methods of tissue characterisation and emerging technical advances present new
      avenues for this modality, securing its place as the noninvasive imaging tool of
      the future. 

PMID- 24298180
TI  - Eosinophilic oesophagitis--a common disease, newly recognised.
AB  - Eosinophilic oesophagitis is a clinico-pathologic diagnosis that describes
      patients with dysphagia (intermittent or continuous), food bolus obstruction or
      regurgitation, where endoscopy and biopsy reveals high concentrations of
      eosinophils in the lining of the oesophagus. At endoscopy, the presence of rings
      (trachealisation), furrows, micro-abscesses and strictures may be noted, but
      sometimes the appearance is normal. Hence biopsy is essential in every patient
      with dysphagia. The condition, recognised 25 years ago as a separate disease
      entity, not related to gastro-oesophageal reflux, is now becoming common. It is
      important for all general physicians to recognise this and make an accurate
      diagnosis in order to give specific treatment. This may involve topical steroids,
      leukotreine D4 antagonists, dietary exclusions and dilatations. 

PMID- 24298181
TI  - Investigation and management of the solitary pulmonary nodule.
AB  - With the advent of multi-detector computed tomography, the identification of
      solitary pulmonary nodules is becoming ever more common. Although the prevalence
      of malignancy in a high risk population is only 1-1.5%, accurate identification
      of malignant nodules is essential to allow optimal treatment. In this article we
      review the most common causes of solitary pulmonary nodules and discuss
      diagnostic algorithms as well as some of the novel diagnostic imaging techniques
      in development. 

PMID- 24298182
TI  - New modalities for non-invasive ventilation.
AB  - There is now substantial evidence supporting the use of non-invasive ventilation
      in acute hypercpanic exacerbations of chronic respiratory failure, and early
      trials show nocturnal ventilatory support may benefit chronic heart failure
      patients with sleep disordered breathing. Attention is now being focused on
      innovative modes which adapt respiratory support to the user's ventilatory
      pattern, eg adaptive service ventilation and assured volume delivery
      'intelligent' ventilation. 

PMID- 24298183
TI  - Substance misuse in the older person: setting higher standards.
AB  - The number of older substance misusers requiring treatment is likely to double
      over the next couple of decades. However, there are many misconceptions and myths
      about this often hidden population. Older people misuse alcohol, nicotine,
      prescription medication and illicit drugs. All indications are that this is
      increasing. This may be as a cause and/or the result of physical or mental
      illness, and the consequent morbidity and mortality are costly to the patient,
      their families and society. Patients present to a very wide variety of social and
      medical care settings, so screening and assessment for substance use are of
      paramount importance. This provides the opportunity to determine to what extent
      the substance problem is related to the presentation, which may be subtle and
      atypical in older people. Since evidence is accumulating of the benefit of
      treatment for substance problems in the older population, this group should not
      be marginalised and neglected by practitioners, researchers, educators and policy
      makers. 

PMID- 24298184
TI  - Joint hypermobility: emerging disease or illness behaviour?
AB  - Joint hypermobility syndrome is a common clinical entity which is much
      misunderstood, overlooked, misdiagnosed and mistreated. It was first described in
      the 1960s as a purely musculoskeletal condition due to joint laxity and
      hypermobility occurring in otherwise healthy individuals. Some four decades later
      it is now perceived to be a multi-systemic heritable disorder of connective
      tissue with manifestations occurring far beyond the confines of the locomotor
      system and with ramifications potentially affecting most, if not all, of the
      bodily systems in one way or another. Most authorities in the field find it
      clinically indistinguishable from the Ehlers-Danlos syndrome--hypermobility type
      (formerly, EDS type III). In >50% of patients the diagnosis is delayed for >=10
      years. Failure to diagnose and treat the condition correctly results in needless
      pain and suffering and in many patients to a progressive decline in their quality
      of life and in some to a loss of independence.

PMID- 24298185
TI  - New oral anticoagulants: their role and future.
AB  - After 60 years in which warfarin has been the only practical oral anticoagulant,
      a number of new oral anticoagulants are entering practice. These drugs differ in
      a several important respects from warfarin; most notably they have a reliable
      dose-response effect which means they can be given without the need for
      monitoring. Their simpler metabolism and mode of action also results in fewer
      interactions with other drugs and with diet. However, some of their other
      properties such as renal clearance (to varying degrees), short half-life and lack
      of an available antidote may slow their rate of introduction. Large trials have
      established their non-inferiority to warfarin in a number of indications and in
      some cases their superiority. To date they have been licensed for prophylaxis
      following high risk orthopaedic procedures, non-valvular atrial fibrillation and
      treatment of venous thromboembolism, but is not clear that they will supplant
      warfarin in all areas. 

PMID- 24298186
TI  - Treatment of acute myeloid leukaemia.
AB  - Acute myeloid leukaemia is a heterogeneous disease that occurs in all age groups
      but peaks in older age at around a median of 69-70 years where it has a frequency
      of 13-15/100,00/annum. With the changing demographics, the number of cases will
      increase in line with the older population. As the only treatment with curative
      intent is intensive chemotherapy, this presents an immediate therapeutic
      challenge for the majority of the disease. 

PMID- 24298187
TI  - Personalised medicine and genetic prediction--are we there yet?
AB  - A working definition of personalised medicine is the delivery of a tailor-made
      treatment to the right patient at the right time. How close have recent advances
      in genetics come to realising this in the clinic? 

PMID- 24298188
TI  - Nutrition, older people and the end of life.
AB  - Older patients are at increased risk of malnutrition, resulting in higher
      mortality and morbidity. It is important to address nutritional need early in
      order to prevent or mitigate these adverse outcomes. Decisions about nutrition
      and hydration for older people presenting with acute illness or evolving multiple
      long-term conditions present great difficulty to all involved. Clinicians are
      more likely to encounter such situations as the population of older people with
      frailty syndromes expands. The clinical evidence base to guide such decisions is
      sparse and largely unhelpful. Clinicians must recognise their role in these
      difficult decisions. In addition to familiarity with the clinical evidence base,
      they must be fully informed of the legal, professional and moral context of the
      decisions with which they are faced. Responsible clinicians have a professional
      duty to elicit, understand and weigh the views of their patient, and where
      necessary their representatives. This can only be undertaken through a process of
      facilitated patient choice utilising the available legal and professional
      decision-making frameworks. Any decision relating to clinically assisted
      nutrition and/or hydration in a frail older person who is considered to be
      nearing the end of their life must also include explicit consideration of the
      needs of that individual for formalised palliative care. 

PMID- 24298189
TI  - Managing parental groups during early childhood: New challenges faced by Swedish
      child health-care nurses.
AB  - The purpose of this study was to describe child health centre (CHC) nurses' views
      of managing parental groups during early childhood. All 311 CHC nurses working
      within the Swedish CHC system in one county were asked to complete a web-based
      questionnaire. Findings showed that although the CHC nurses were experienced,
      several found group leadership challenging and difficult. The need for
      specialized groups for young parents, single parents and parents whose first
      language was not Swedish was identified by 57% of the nurses. The CHC nurses
      found the participation of fathers in their parental groups to be low (an
      estimate of 10-20%), and 30% of the nurses made special efforts to make the
      fathers participate. Education in group dynamics and group leadership can
      strengthen CHC nurses in managing parental groups. It is recommended that
      specialized parental groups are organized by a few family centres so CHC nurses
      can develop their skill in managing such groups. 

PMID- 24298191
TI  - Development and evaluation of the EOL-ICDQ as a measure of experiences, attitudes
      and knowledge in end-of-life in patients living with an implantable cardioverter
      defibrillator.
AB  - BACKGROUND: Due to extended indications and resynchronization therapy, many
      implantable cardioverter defibrillator (ICD) recipients will experience
      progressive co-morbid conditions and will be more likely to die of causes other
      than cardiac death. It is therefore important to elucidate the ICD patients'
      preferences when nearing end-of-life. Instead of avoiding the subject of end-of
      life, a validated questionnaire may be helpful to explore patients' experiences
      and attitudes about end-of-life concerns and to assess knowledge of the function
      of the ICD in end-of-life. Validated instruments assessing patients' perspective
      concerning end-of-life issues are scarce. AIM: The purpose of this study was to
      develop and evaluate respondent satisfaction and measurement properties of the
      'Experiences, Attitudes and Knowledge of End-of-Life Issues in Implantable
      Cardioverter Defibrillator Patients' Questionnaire' (EOL-ICDQ). METHODS: The
      instrument was tested for validity, respondent satisfaction, and for homogeneity
      and stability in the Swedish language. An English version of the EOL-ICDQ was
      validated, but has not yet been pilot tested. RESULTS: The final instrument
      contained three domains, which were clustered into 39 items measuring:
      experiences (10 items), attitudes (18 items), and knowledge (11 items) of end-of
      life concerns in ICD patients. In addition, the questionnaire also contained
      items on socio-demographic background (six items) and ICD-specific background
      (eight items). The validity and reliability properties were considered
      sufficient. CONCLUSIONS: The EOL-ICDQ has the potential to be used in clinical
      practice and future research. Further studies are needed using this instrument in
      an Anglo-Saxon context with a sample of English-speaking ICD recipients.

PMID- 24298192
TI  - Combined cardioprotectant and antithrombotic actions of platelet P2Y12 receptor
      antagonists in acute coronary syndrome: just what the doctor ordered.
AB  - Since the P2Y12 receptor antagonists were first introduced, they have been
      extensively tested in patients with acute coronary syndrome and are now standard
      of care. These antiplatelet drugs are very effective in reducing subsequent
      cardiovascular events, stent thromboses, and mortality in patients with acute
      myocardial infarction undergoing reperfusion therapy. Although the prevailing
      view is that their benefit derives from their antithrombotic properties, other
      unrelated pleiotropic effects appear to be equally beneficial. Accumulating
      clinical and animal evidence indicates that, if present at the time of
      reperfusion, these drugs have a direct anti-infarct effect similar to that of
      ischemic postconditioning. Four oral antagonists have been developed in rapid
      succession: ticlopidine, clopidogrel, prasugrel, and ticagrelor. Each agent had a
      more consistent and rapid onset of action than the previous one, and this has
      correlated with improved clinical outcomes when given early in treatment.
      Unfortunately, gut absorption causes an appreciable delay in the onset of effect,
      especially when morphine is used, and the constant push to minimize the door-to
      balloon time has made it difficult to achieve adequate platelet inhibition at the
      time of percutaneous coronary intervention with an oral agent. An intravenous
      P2Y12 antagonist such as cangrelor may optimize treatment because it produces
      nearly maximal inhibition of platelet aggregation within minutes. If antiplatelet
      agents do protect through postconditioning's mechanism, then they would render
      any other intervention that protects through that mechanism redundant. Indeed,
      animals treated with cangrelor cannot be further protected by pre- or
      postconditioning. However, interventions that use a different mechanism such as
      mild hypothermia or cariporide, a Na(+)-H(+) exchange blocker, do add to
      cangrelor's protection. Future research should be directed toward identifying
      interventions that can augment the protection from antiplatelet therapy and
      finding a way to optimize P2Y12 inhibition at reperfusion in all patients. 

PMID- 24298193
TI  - The Changing Bases of Segregation in the United States.
AB  - The nature and organization of segregation shifted profoundly in the United
      States over the course of the twentieth century. During the first two-thirds of
      the century, segregation was defined by the spatial separation of whites and
      blacks. What changed over time was the level at which this racial separation
      occurred, as macro-level segregation between states and counties gave way
      steadily to micro-level segregation between cities and neighborhoods. During the
      last third of the twentieth century, the United States moved toward a new regime
      of residential segregation characterized by moderating racial-ethnic segregation
      and rising class segregation, yielding a world in which the spatial organization
      of cities and the location of groups and people within them will increasingly be
      determined by an interaction of race and class and in which segregation will stem
      less from overt prejudice and discrimination than from political decisions about
      land use, such as density zoning.

PMID- 24298194
TI  - An Integrative Bayesian Modeling Approach to Imaging Genetics.
AB  - In this paper we present a Bayesian hierarchical modeling approach for imaging
      genetics, where the interest lies in linking brain connectivity across multiple
      individuals to their genetic information. We have available data from a
      functional magnetic resonance (fMRI) study on schizophrenia. Our goals are to
      identify brain regions of interest (ROIs) with discriminating activation patterns
      between schizophrenic patients and healthy controls, and to relate the ROIs'
      activations with available genetic information from single nucleotide
      polymorphisms (SNPs) on the subjects. For this task we develop a hierarchical
      mixture model that includes several innovative characteristics: it incorporates
      the selection of ROIs that discriminate the subjects into separate groups; it
      allows the mixture components to depend on selected covariates; it includes prior
      models that capture structural dependencies among the ROIs. Applied to the
      schizophrenia data set, the model leads to the simultaneous selection of a set of
      discriminatory ROIs and the relevant SNPs, together with the reconstruction of
      the correlation structure of the selected regions. To the best of our knowledge,
      our work represents the first attempt at a rigorous modeling strategy for imaging
      genetics data that incorporates all such features.

PMID- 24298195
TI  - Particle Detector Applications in Medicine.
AB  - Selected particle detectors are described which find an application in medicine
      and have been the topic of presentations at the 2013 Vienna Conference of
      Instrumentation (VCI).

PMID- 24298196
TI  - Mindfulness and rumination as predictors of persistence with a distress tolerance
      task.
AB  - Distress tolerance (DT) is a proposed transdiagnostic factor in psychopathology,
      yet sources of individual differences in DT are largely unknown. The present
      study examined mindfulness and rumination facets as predictors of persistence on
      a standardized DT task (mirror tracing). Acting with awareness (a facet of
      mindfulness) and reflection (a potentially adaptive form of rumination) predicted
      increased DT. Increased task-induced skin conductance reactivity predicted
      decreased DT. These results held after controlling for task skill and subjective
      and heart rate reactivity. Together, these results suggest that teaching skills
      to promote mindful awareness and reflection hold promise as interventions to
      enhance DT.

PMID- 24298197
TI  - Analyzing Propensity Matched Zero-Inflated Count Outcomes in Observational
      Studies.
AB  - Determining the effectiveness of different treatments from observational data,
      which are characterized by imbalance between groups due to lack of randomization,
      is challenging. Propensity matching is often used to rectify imbalances among
      prognostic variables. However, there are no guidelines on how appropriately to
      analyze group matched data when the outcome is a zero inflated count. In
      addition, there is debate over whether to account for correlation of responses
      induced by matching, and/or whether to adjust for variables used in generating
      the propensity score in the final analysis. The aim of this research is to
      compare covariate unadjusted and adjusted zero-inflated Poisson models that do
      and do not account for the correlation. A simulation study is conducted,
      demonstrating that it is necessary to adjust for potential residual confounding,
      but that accounting for correlation is less important. The methods are applied to
      a biomedical research data set.

PMID- 24298198
TI  - Globalization and Inequality: Explaining American Exceptionalism.
AB  - Globalization creates pressure for greater inequality throughout the world, but
      these pressures are expressed more fully in the United States than in other
      developed nations. Although the distribution of US income before taxes is no more
      unequal than other nations, after taxes it is considerably less egalitarian. This
      occurs because of specific institutional arrangements that fail to redistribute
      income effectively and allow the pressures of globalization to be fully realized.
      These arrangements represent a shift from the past and were deliberately enacted
      over the past two decades with divergent consequences for those at the top and
      bottom of the socioeconomic hierarchy. The realignment of the US political
      economy can ultimately be traced to America's legacy of racism. Once leaders in
      the Democratic party sought to include African Americans in the benefits of
      Roosevelt's New Deal, support for economic populism evaporated in the middle and
      working classes. The advantage of the wealth is further enhanced by a political
      system in which those with money are better able to have their interests served
      legislatively than the poor or working classes.

PMID- 24298200
TI  - Isotope Effects and Temperature Dependences in the Action of the Glucose
      Dehydrogenase of the Mesophilic Bacterium Bacillus megaterium.
AB  - The glucose dehydrogenase of the mesophilic bacterium Bacillus megaterium
      (optimal growth around 35  degrees C) exhibits non-linear Eyring temperature
      dependences from 25 to 55  degrees C in its catalysis of the oxidation by hydride
      transfer to NAD+ of the beta-anomers of 1-h-D-glucose and 1-d-D-glucose (rate
      constant kcat/KMbeta). A break around 300K separates a high-T region from a low-T
      region. In the high-T region, isotopic enthalpies of activation within a
      considerable experimental error are equal to zero. In the low-T region, the
      enthalpies of activation are roughly equal for the isotopic substrates but are
      different from zero. An alternative treatment with Eyring plots taken as
      effectively linear produces enthalpies of activation having the unusual feature
      of being larger for the H-substrate (26 kJ/mol) than for the D-substrate (21
      kJ/mol). Compensation of the enthalpic effect by a more positive entropy for the
      H-substrate then reproduces the isotope effects. For oxidation by NADP+ of the
      same pair of isotopic glucose substrates, catalysis by the glucose dehydrogenase
      of Thermoplasma acidophilum, a thermophilic archaeon, leads to temperature
      dependences characterized by a high-T region and a low-T region separated by a
      gentle thermal transition (K. Anandarajah, K.B. Schowen, and R.L. Schowen, Z.
      phys. Chem. 2008, 222, 1333-1347). Tentative approaches to a mechanistic
      interpretation of both cases rely on models featuring configurational searches of
      the enzyme for tunneling states, followed by hydrogen-transfer tunneling,
      although explanations can be constructed also on the basis of simple transition
      state stabilization without tunnelling.

PMID- 24298199
TI  - Motivational Pathways to STEM Career Choices: Using Expectancy-Value Perspective
      to Understand Individual and Gender Differences in STEM Fields.
AB  - The United States has made a significant effort and investment in STEM education,
      yet the size and the composition of the STEM workforce continues to fail to meet
      demand. It is thus important to understand the barriers and factors that
      influence individual educational and career choices. In this article, we conduct
      a literature review of the current knowledge surrounding individual and gender
      differences in STEM educational and career choices, using expectancy-value theory
      as a guiding framework. The overarching goal of this paper is to provide both a
      well-defined theoretical framework and complementary empirical evidence for
      linking specific sociocultural, contextual, biological, and psychological factors
      to individual and gender differences in STEM interests and choices. Knowledge
      gained through this review will eventually guide future research and
      interventions designed to enhance individual motivation and capacity to pursue
      STEM careers, particularly for females who are interested in STEM but may be
      constrained by misinformation or stereotypes.

PMID- 24298201
TI  - Renal dysfunction is an independent risk factor for mortality after liver
      resection and the main determinant of outcome in posthepatectomy liver failure.
AB  - Introduction. The aim of this study was to assess the interaction of liver and
      renal dysfunction as risk factors for mortality after liver resection. Materials
      and Methods. A retrospective analysis of 501 patients undergoing liver resection
      in a single unit was undertaken. Posthepatectomy liver failure (PHLF) was defined
      according to the International Study Group of Liver Surgery (ISGLS) definition
      (assessed on day 5) and renal dysfunction according to RIFLE criteria. 90-day
      mortality was recorded. Results. Twenty-three patients died within 90 days of
      surgery (4.6%). The lowest mortality occurred in patients without evidence of
      PHLF or renal dysfunction (2.7%). The mortality rate in patients with isolated
      PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes
      (P = 0.028), renal dysfunction (P = 0.030), and PHLF on day 5 (P = 0.011) were
      independent predictors of 90-day mortality. Discussion. PHLF and postoperative
      renal dysfunction are independent predictors of 90-day mortality following liver
      resection but the predictive value for mortality is significantly higher when
      failure of both organ systems occurs simultaneously. 

PMID- 24298203
TI  - Men's and women's migration in coastal Ghana: An event history analysis.
AB  - This article uses life history calendar (LHC) data from coastal Ghana and event
      history statistical methods to examine inter-regional migration for men and
      women, focusing on four specific migration types: rural-urban, rural-rural, urban
      urban, and urban-rural. Our analysis is unique because it examines how key
      determinants of migration- including education, employment, marital status, and
      childbearing-differ by sex for these four types of migration. We find that women
      are significantly less mobile than men overall, but that more educated women are
      more likely to move (particularly to urban areas) than their male counterparts.
      Moreover, employment in the prior year is less of a deterrent to migration among
      women. While childbearing has a negative effect on migration, this impact is
      surprisingly stronger for men than for women, perhaps because women's search for
      assistance in childcare promotes migration. Meanwhile, being married or in union
      appears to have little effect on migration probabilities for either men or women.
      These results demonstrate the benefits of a LHC approach and suggest that
      migration research should further examine men's and women's mobility as it
      relates to both human capital and household and family dynamics, particularly in
      developing settings.

PMID- 24298202
TI  - Deep brain stimulation for the treatment of Parkinson's disease: efficacy and
      safety.
AB  - Deep brain stimulation (DBS) surgery has become increasingly utilized in the
      treatment of advanced Parkinson's disease. Over the past decade, a number of
      studies have demonstrated that DBS is superior to best medical management in
      appropriately selected patients. The primary targets for DBS in Parkinson's
      disease include the subthalamic nucleus and the internal segment of the globus
      pallidus, both of which improve the cardinal motor features in Parkinson's
      disease. Recent randomized studies have revealed that both targets are similarly
      effective in treating the motor symptoms of Parkinson's disease, but emerging
      evidence suggests that the globus pallidus may be the preferred target in many
      patients, based on differences in nonmotor outcomes. Here, we review appropriate
      patient selection, and the efficacy and safety of DBS therapy in Parkinson's
      disease. Best outcomes are achieved if the problems of the individual patient are
      considered when evaluating surgical candidates and considering whether the
      subthalamic nucleus or the globus pallidus internus should be targeted.

PMID- 24298204
TI  - Practitioner-level predictors of alcohol problems detection and management
      activities.
AB  - : The alcohol health services literature suggests that a potential problem with
      promoting secondary prevention is an existing educational focus on alcohol
      dependency. AIMS: This study explores practitioner-level predictors of health
      professionals' self-reported detection and management activities in an effort to
      inform this question. PARTICIPANTS: The participants consisted of a random sample
      of licensed physicians and nurse practitioners in a northern California county.
      MEASUREMENT: Participants completed a self-administered questionnaire on beliefs
      and practices regarding patients with alcohol problems and at-risk drinkers.
      FINDINGS: The results indicate that prior alcohol education predicted clinical
      practices to address known or suspected drinking problems, but not those at-risk
      or without observable symptoms. In addition, stigmatizing beliefs about problem
      drinkers discouraged use of blood tests even when awareness of a drinking problem
      existed. CONCLUSIONS: The conclusions are that existing models of alcohol
      education appear to convey a tertiary focus, and do not cover secondary
      prevention sufficiently to challenge the deficits and beliefs that discourage
      early detection and intervention.

PMID- 24298205
TI  - Approximate single-diode photovoltaic model for efficient I-V characteristics
      estimation.
AB  - Precise photovoltaic (PV) behavior models are normally described by nonlinear
      analytical equations. To solve such equations, it is necessary to use iterative
      procedures. Aiming to make the computation easier, this paper proposes an
      approximate single-diode PV model that enables high-speed predictions for the
      electrical characteristics of commercial PV modules. Based on the experimental
      data, statistical analysis is conducted to validate the approximate model.
      Simulation results show that the calculated current-voltage (I-V) characteristics
      fit the measured data with high accuracy. Furthermore, compared with the existing
      modeling methods, the proposed model reduces the simulation time by approximately
      30% in this work. 

PMID- 24298206
TI  - Acute toxicity and genotoxic activity of avocado seed extract (Persea americana
      Mill., c.v. Hass).
AB  - The use of vegetal extracts requires toxicological and genotoxic evaluations to
      establish and verify safety before being added to human cosmetic, pharmaceutical
      medicine, or alimentary products. Persea americana seeds have been used in
      traditional medicine as treatment for several diseases. In this work, the
      ethanolic seed extract of Persea americana was evaluated with respect to its
      genotoxic potential through micronucleus assay in rodents. The frequency of
      micronuclei in groups of animals treated with avocado seed extract showed no
      differences compared to the negative control (vehicle); therefore, it is
      considered that the avocado seed extract showed no genotoxic activity in the
      micronucleus test. 

PMID- 24298207
TI  - Effect of forging parameters on low cycle fatigue behaviour of Al/basalt short
      fiber metal matrix composites.
AB  - This paper deals with metal matrix composites (MMCs) of Al 7075 alloy containing
      different weight percentage (2.5, 5, 7.5, and 10) basalt short fiber
      reinforcement and unreinforced matrix alloy. The samples were produced by the
      permanent stir casting technique. The casting ingots were cut into blanks to be
      forged in single stage and double stage, using MN press and graphite-based
      lubricant. The microstructures and fatigue properties of the matrix alloy and MMC
      samples were investigated in the as cast state and in the single and double stage
      forging operations. The microstructure results showed that the forged sample had
      a uniform distribution of the basalt short fiber throughout the specimens.
      Evaluation of the fatigue properties showed that the forged samples had higher
      values than those of the as cast counterparts. After forging, the enhancement of
      the fatigue strength of the matrix alloy was so significant and high in the case
      of 2.5 and 5.0 wt. percentage basalt short fiber reinforced MMC, and there was no
      enhancement in 7.5 and 10 weight percentages short fiber reinforced MMCs. The
      fracture damage was mainly due to decohesion at the matrix-fiber interface. 

PMID- 24298208
TI  - Radiation sterilization of anthracycline antibiotics in solid state.
AB  - The impact of ionizing radiation generated by a beam of electrons of 25-400 kGy
      on the stability of such analogs of anthracycline antibiotics as daunorubicin
      (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR
      results, it was established that unstable free radicals decay exponentially with
      the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation.
      Radiation-induced structural changes were analyzed with the use of
      spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM).
      A chromatographic method (HPLC-DAD) was applied to assess changes in the contents
      of the analogs in the presence of their impurities. The study showed that the
      structures of the analogs did not demonstrate any significant alterations at the
      end of the period necessary for the elimination of unstable free radicals. The
      separation of main substances and related substances (impurities and potential
      degradation products) allowed determining that no statistically significant
      changes in the content of particular active substances occurred and that their
      conversion due to the presence of free radicals resulting from exposure to an
      irradiation of 25 kGy (prescribed to ensure sterility) was not observed. 

PMID- 24298209
TI  - Explicit nonlinear finite element geometric analysis of parabolic leaf springs
      under various loads.
AB  - This study describes the effects of bounce, brake, and roll behavior of a bus
      toward its leaf spring suspension systems. Parabolic leaf springs are designed
      based on vertical deflection and stress; however, loads are practically derived
      from various modes especially under harsh road drives or emergency braking.
      Parabolic leaf springs must sustain these loads without failing to ensure bus and
      passenger safety. In this study, the explicit nonlinear dynamic finite element
      (FE) method is implemented because of the complexity of experimental testing A
      series of load cases; namely, vertical push, wind-up, and suspension roll are
      introduced for the simulations. The vertical stiffness of the parabolic leaf
      springs is related to the vehicle load-carrying capability, whereas the wind-up
      stiffness is associated with vehicle braking. The roll stiffness of the parabolic
      leaf springs is correlated with the vehicle roll stability. To obtain a better
      bus performance, two new parabolic leaf spring designs are proposed and
      simulated. The stress level during the loadings is observed and compared with its
      design limit. Results indicate that the newly designed high vertical stiffness
      parabolic spring provides the bus a greater roll stability and a lower stress
      value compared with the original design. Bus safety and stability is promoted, as
      well as the load carrying capability. 

PMID- 24298210
TI  - Antioxidative and anticholinesterase activity of Cyphomandra betacea fruit.
AB  - Cyphomandra betacea is one of the underutilized fruits which can be found in
      tropical and subtropical countries. This study was conducted to determine the
      antioxidant activity and phytochemical contents in different parts (i.e., flesh
      and peel) of the fruits. Antioxidants were analyzed using DPPH and ABTS free
      radical scavenging assays as well as FRAP assay. Anticholinesterase activity was
      determined using enzymatic assay using acetyl cholinesterase enzyme. For 80%
      methanol extract, the peel of the fruit displayed higher antioxidant activity in
      both FRAP and ABTS free radical scavenging assays while the flesh displayed
      higher antioxidant activity in the DPPH assay. Total phenolic and total flavonoid
      content were higher in the peel with the values of 4.89 +/- 0.04 mg gallic acid
      equivalent (GAE)/g and 3.36 +/- 0.01 mg rutin equivalent (RU)/g, respectively.
      Total anthocyanin and carotenoid content were higher in the flesh of the fruit
      with the values of 4.15 +/- 0.04 mg/100 g and 25.13 +/- 0.35 mg/100 g. The
      anticholinesterase was also higher in the peel of C. betacea. The same trends of
      phytochemicals, antioxidant, and anticholinesterase were also observed in the
      distilled water extracts. These findings suggested that C. betacea has a
      potential as natural antioxidant-rich nutraceutical products. 

PMID- 24298211
TI  - Spatiotemporal distribution and population structure of Monokalliapseudes
      schubarti (Tanaidacea: Kalliapseudidae) in an estuary in Southern Brazil.
AB  - Monokalliapseudes schubarti is an endemic tanaidacean microcrustacean from
      southeastern Brazil to Uruguay inhabiting low energy estuaries. Saco da Fazenda
      is located in the estuary of the Itajai-Acu River, state of Santa Catarina,
      Brazil. It is exposed to strong anthropic impact and receives intensive flows of
      domestic wastewater, solid residues, and drainage activities. Specimens of M.
      schubarti were collected monthly, in the intertidal and subtidal regions of Saco
      da Fazenda, in four stations defined as a function of the physiography of the
      environment during the period of July 2003 to June 2004. Fecundity values were
      high, with continuous reproductive activity during the whole period of study. The
      greatest population densities were observed in the intertidal region, where they
      are nevertheless intensely consumed by birds, swimming crabs, and fish. This
      species represents a fundamental link in the food chain of Saco da Fazenda,
      transferring energy from the detritus level to higher trophic levels. Habitat
      disturbance and high organic matter may represent factors controlling the
      distribution of populations of M. schubarti. For this reason, the species may be
      used to monitor anthropic effects in estuarine areas. 

PMID- 24298212
TI  - Investigation of biofilm forming ability in Staphylococci causing bovine mastitis
      using phenotypic and genotypic assays.
AB  - A total of 40 S. aureus and 68 coagulase negative Staphylococcus (CNS) isolates
      from bovine subclinical mastitis were investigated for their ability to form
      biofilm as one of the most important virulence factors.Using Congo Red Agar (CRA)
      method, 32.5%, 35%, and 32.5% of S. aureus strains were strong, intermediate, and
      negative biofilm producers, while in CNS the percentages were 29.5%, 42.6%, and
      27.9%, respectively. By microtiter plate (MTP) method, 52.5%, 27.5%, and 20% of
      S. aureus isolates were strong, moderate, and weak biofilm producers, while in
      CNS the percentages were 44%, 30.9%, and 19.2%, respectively. Indian ink staining
      was used to detect the EPS layer of biofilm producers. All isolates were screened
      for presence of biofilm related genes, eno, icaA, icaD, and bap. In S. aureus
      isolates, the positive rates of eno, icaA, icaD, and bap genes were 75%, 15%,
      62.5%, and 2.5% while in CNS were 92.6%, 5.9%, 47.1%, and 4.4%, respectively. The
      eno gene had the highest rate while the bap gene had the lowest rate. Presence of
      icaA and icaD genes was not always correlated with biofilm production. This study
      demonstrated high prevalence of Staphylococcus biofilm producers among bovine
      mastitis in Egypt. Therefore, attention must be paid toward implementation of new
      ways for effective treatment of such infections. 

PMID- 24298213
TI  - The role of clomipramine in potentiating the teratogenic effects of caffeine in
      pregnant rats: a histopathological study.
AB  - Since little is known about the teratogenic effects of clomipramine used
      concurrently with caffeine during the organogenesis period, the aim of this study
      was to test the teratogenic effects of a coadministration of caffeine and
      clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups,
      randomly. The first group (control) received 0.5 mL of normal saline.
      Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third
      groups, respectively. The fourth and fifth groups received caffeine in doses of
      60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of
      40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given
      clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses
      were removed on the 17th day of pregnancy and studied in terms of microscopic and
      macroscopic morphological features. Fetuses of rats receiving high doses of
      caffeine or combinations of caffeine and clomipramine showed a significant rate
      of cleft palate development, open eyelids, mortality, torsion anomalies,
      shrinkage of skin, and subcutaneous haemorrhage (P <= 0.001). This study
      concludes that caffeine in high doses or the simultaneous administration of
      caffeine and clomipramine leads to teratogenicity. 

PMID- 24298214
TI  - Enhancement of antioxidant and isoflavones concentration in gamma irradiated
      soybean.
AB  - Serbian soybean genotype Ana was gamma irradiated at doses of 1, 2, 4, and 10 kGy
      in order to evaluate the influence of gamma irradiation on isoflavone (genistein,
      daidzein, and their glycosides genistin and daidzin) contents and hydroxyl
      radical scavenging effect (HRSE). The increase in genistin and daidzin contents
      as well as antioxidant activities was observed especially at doses of 4 and 10
      kGy. Results were also compared with our previous results relating to total
      phenol content (TPC), DPPH radical scavenger capacity (DPPH RSC), and ferric
      reducing antioxidant power (FRAP). Our results indicated that doses up to 10 kGy
      improve the antioxidant activities of soybean and also nutritional quality with
      respect to isoflavone content. All results were analyzed by multivariate
      techniques (correlation matrix calculation and autoscaling transformation of
      data). Significant positive correlations were observed between genistin, daidzin,
      DPPH RSC, and HRSE. 

PMID- 24298215
TI  - A study on the effect of metabolic heat generation on biological tissue freezing.
AB  - The effect of metabolic heat generation on the freezing of biological tissue has
      been studied. Quasi-steady approximation is used to solve the Pennes bioheat
      equation in tissues. Temperature profile and motion of freezing interfaces are
      obtained for different values of metabolic heat generation. It is observed that
      metabolism has a significant effect on freezing of biological tissues during
      cryosurgery. 

PMID- 24298216
TI  - A survey of keystroke dynamics biometrics.
AB  - Research on keystroke dynamics biometrics has been increasing, especially in the
      last decade. The main motivation behind this effort is due to the fact that
      keystroke dynamics biometrics is economical and can be easily integrated into the
      existing computer security systems with minimal alteration and user intervention.
      Numerous studies have been conducted in terms of data acquisition devices,
      feature representations, classification methods, experimental protocols, and
      evaluations. However, an up-to-date extensive survey and evaluation is not yet
      available. The objective of this paper is to provide an insightful survey and
      comparison on keystroke dynamics biometrics research performed throughout the
      last three decades, as well as offering suggestions and possible future research
      directions. 

PMID- 24298217
TI  - Video denoising based on a spatiotemporal Kalman-bilateral mixture model.
AB  - We propose a video denoising method based on a spatiotemporal Kalman-bilateral
      mixture model to reduce the noise in video sequences that are captured with low
      light. To take full advantage of the strong spatiotemporal correlations of
      neighboring frames, motion estimation is first performed on video frames
      consisting of previously denoised frames and the current noisy frame by using
      block-matching method. Then, current noisy frame is processed in temporal domain
      and spatial domain by using Kalman filter and bilateral filter, respectively.
      Finally, by weighting the denoised frames from Kalman filtering and bilateral
      filtering, we can obtain a satisfactory result. Experimental results show that
      the performance of our proposed method is competitive when compared with state-of
      the-art video denoising algorithms based on both peak signal-to-noise-ratio and
      structural similarity evaluations. 

PMID- 24298219
TI  - The inhomogeneous waves in a rotating piezoelectric body.
AB  - This paper presents the analysis and numerical results of rotation, propagation
      angle, and attenuation angle upon the waves propagating in the piezoelectric
      body. Via considering the centripetal and Coriolis accelerations in the
      piezoelectric equations with respect to a rotating frame of reference, wave
      velocities and attenuations are derived and plotted graphically. It is
      demonstrated that rotation speed vector can affect wave velocities and make the
      piezoelectric body behaves as if it was damping. Besides, the effects of
      propagation angle and attenuation angle are presented. Critical point is found
      when rotation speed is equal to wave frequency, around which wave characteristics
      change drastically. 

PMID- 24298218
TI  - Invasive fungal rhinosinusitis versus bacterial rhinosinusitis with orbital
      complications: a case-control study.
AB  - BACKGROUND: Invasive fungal rhinosinusitis with orbital complications (IFSwOC) is
      a life-threatening condition. The incidence of mortality has been reported to be
      up to 80 percent. This study was conducted to determine the risk factors,
      presentations, clinical, and imaging findings that could help to manage this
      condition promptly. METHODS: We conducted a case-control study of 100 patients
      suffering from rhinosinusitis with orbital complications. The risk factors,
      clinical presentations, radiological findings, medical and surgical managements,
      durations of hospital stay, and mortality rate data were collected. RESULTS:
      Sixty-five patients were diagnosed with IFSwOC, while the other thirty-five
      patients composed the control group. The most important risk factor for IFSwOC
      was diabetes mellitus. Visual loss and diplopia were the significant symptom
      predictors. The significant clinical predictors were nasal crust, oculomotor
      nerve, and optic nerve involvement. The CT findings of IFSwOC were sinus wall
      erosion and hyperdensity lesions. The mortality rate was 25.71 percent in the
      IFSwOC group and 3.17 percent in the control group. CONCLUSIONS: Invasive fungal
      rhinosinusitis with orbital complications is symptomatic of a high mortality
      rate. The awareness of a patient's risk factors, the presenting symptoms, signs
      of fungal invasion, and aggressive management will determine the success of any
      treatment procedures.

PMID- 24298220
TI  - A characterization of the compound multiparameter hermite gamma distribution via
      Gauss's principle.
AB  - We consider the class of those distributions that satisfy Gauss's principle (the
      maximum likelihood estimator of the mean is the sample mean) and have a parameter
      orthogonal to the mean. It is shown that this so-called "mean orthogonal class"
      is closed under convolution. A previous characterization of the compound gamma
      characterization of random sums is revisited and clarified. A new
      characterization of the compound distribution with multiparameter Hermite count
      distribution and gamma severity distribution is obtained. 

PMID- 24298222
TI  - Commentary on fukushima and beneficial effects of low radiation.
AB  - Approximately 160,000 people evacuated the area around the Fukushima Dai-ichi NPP
      shortly after it was damage by the earthquake and tsunami. The evacuation order
      applied to 70,000 of them, while the other 90,000 left voluntarily and returned
      soon afterward. After more than two years, most of the 70,000 are still not
      allowed to return to their homes. The 1100 disaster-related deaths caused by the
      evacuation order show that this pre-cautionary action, taken to minimize cancer
      risks, was not "conservative." In this paper, recent studies are reviewed on the
      consequences of the radioactive releases and on the benefits of many medical
      treatments with low doses of radiation that were carried out until the 1950s,
      before the radiation scare was created. Recent research has shed light on the
      high rate of spontaneous double-strand breaks in DNA and the adaptive protections
      in cells, tissues and humans that are up-regulated by low radiation. These
      defences prevent, repair, remove and replace damage, from all causes including
      external agents. Cancer mortality is reduced. The ICRP's concept of radiation
      risk is wrong. It should revert to its 1934 concept, which was a tolerance dose
      of 0.2 roentgen (r) per day based on more than 35 years of medical experience. 

PMID- 24298221
TI  - Corneal sensitivity in keratoconus: a review of the literature.
AB  - Corneal sensitivity has recently received much attention given the crucial role
      the corneal nerves play in maintaining normal corneal structure and function. An
      increased understanding of the corneal sensitivity and dry eye disease in
      keratoconus, including alterations of the conjunctival cells, may help explain
      the pathogenesis of this disorder. There is histological evidence of the
      involvement of corneal nerves in the pathology of keratoconus and it has been
      suggested that this plays a role in the pathophysiological features and
      progression of the disease. In this review, the impaired corneal sensitivity
      found on keratoconus and corneal sensitivity changes after cross-linking
      performed in patients with keratoconus are reported. 

PMID- 24298223
TI  - A Comparison of In Vivo Cellular Responses to Cs-137 Gamma Rays And 320-kV X
      Rays.
AB  - Research reported here relates to comparing the relative effectiveness of 320-kV
      X rays compared to Cs-137 gamma rays for two in vivo endpoints in C.B-17 mice
      after whole-body exposure: (1) cytotoxicity to bone marrow cells and splenocytes
      evaluated at 24-hours post exposure and (2) bone marrow and spleen reconstitution
      deficits (repopulation shortfalls) evaluated at 6 weeks post exposure. We show
      that cytotoxicity dose-response relationships for bone marrow cells and
      splenocytes are complex, involving negative curvature (decreasing slope as dose
      increases), presumably implicating a mixed cell population comprised of large
      numbers of hypersensitive, modestly radiosensitive, and resistant cells. The
      radiosensitive cells appear to respond with 50% being killed by a dose < 0.5 Gy.
      The X-ray relative biological effectiveness (RBE), relative to gamma rays, for
      destroying bone marrow cells in vivo is > 1, while for destroying splenocytes it
      is < 1. In contrast, dose-response relationships for reconstitution deficits in
      the bone marrow and spleen of C.B-17 mice at 6 weeks after radiation exposure
      were of the threshold type with gamma rays being more effective in causing
      reconstitution deficit. 

PMID- 24298224
TI  - Low-Dose gamma-Irradiation Affects the Survival of Exposed Daphnia and their
      Offspring.
AB  - PURPOSE: To analyze the long-term effects of exposure to low-dose gamma
      irradiation on survival and life span in directly irradiated Daphnia magna and
      their offspring. MATERIALS AND METHODS: One-day-old Daphnia magna were exposed to
      10, 100 and 1000 mGy of acute gamma-rays. The life-span of irradiated and control
      animals, as well as their non-exposed progeny was analyzed. RESULTS: Irradiation
      at dose of 100 and 1000 mGy resulted in a significant decrease in the life span
      of irradiated Daphnia. The data presented here also show that the survival of non
      exposed first-generation offspring of irradiated parents is significantly
      compromised, thus implying the presence of transgenerational effects. CONCLUSION:
      The results of our study show that low-dose irradiation significantly reduces the
      life-span of directly exposed Daphnia and their first-generation offspring. The
      observed compromised viability is most likely attributed to non-targeted effects
      of ionizing radiation.

PMID- 24298225
TI  - The historical use of radiotherapy in the treatment of sinus infections.
AB  - The aim of this paper is to assess the historical role of radiotherapy in the
      treatment of sinus infections. This assessment involved a literature-based review
      of how radiotherapy was used to treat sinus infections in the first half of the
      20(th) century. Low doses of x-rays were used with considerable success to treat
      nearly 3,000 patients of sinus infection in a span of 12 years with these cases
      being reported in leading medical journals as case studies. The mechanism of x
      ray induced reduction of inflammation and increased tissue repair is uncertain
      but appears to be related to the development of a multifactorial and integrative
      anti-inflammatory phenotype. 

PMID- 24298226
TI  - Linear No-Threshold Model VS. Radiation Hormesis.
AB  - The atomic bomb survivor cancer mortality data have been used in the past to
      justify the use of the linear no-threshold (LNT) model for estimating the
      carcinogenic effects of low dose radiation. An analysis of the recently updated
      atomic bomb survivor cancer mortality dose-response data shows that the data no
      longer support the LNT model but are consistent with a radiation hormesis model
      when a correction is applied for a likely bias in the baseline cancer mortality
      rate. If the validity of the phenomenon of radiation hormesis is confirmed in
      prospective human pilot studies, and is applied to the wider population, it could
      result in a considerable reduction in cancers. The idea of using radiation
      hormesis to prevent cancers was proposed more than three decades ago, but was
      never investigated in humans to determine its validity because of the dominance
      of the LNT model and the consequent carcinogenic concerns regarding low dose
      radiation. Since cancer continues to be a major health problem and the age
      adjusted cancer mortality rates have declined by only ~10% in the past 45 years,
      it may be prudent to investigate radiation hormesis as an alternative approach to
      reduce cancers. Prompt action is urged. 

PMID- 24298227
TI  - Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation
      From (90)Y; Consequences for Radiation Induced Bystander Effects.
AB  - In this study, we aimed to establish the emission of UV photons when HPV-G cells
      and associated materials (such as the cell substrate and cell growth media) are
      exposed to low LET radiation. The potential role of UV photons in the secondary
      triggering of biological processes led us to hypothesize that the emission and
      absorption of photons at this wavelength explain some radiation induced
      "bystander effects" that have previously been thought to be chemically mediated.
      Cells were plated in Petri-dishes of two different sizes, having different
      thicknesses of polystyrene (PS) substrate, and were exposed to beta-radiation
      from (90)Y produced by the McMaster Nuclear Reactor. UV measurements were
      performed using a single photon counting system employing an interference-type
      filter for selection of a narrow wavelength range, 340+/-5 nm, of photons.
      Exposure of the cell substrates (which were made of polystyrene) determined that
      UV photons were being emitted as a consequence of beta particle irradiation of
      the Petri-dishes. For a tightly collimated beta-particle beam exposure, we
      observed 167 photons in the detector per unit MUCi in the shielded source for a
      1.76 mm thick substrate and 158 photons/MUCi for a 0.878 mm thick substrate. A
      unit MUCi source activity was equivalent to an exposure to the substrate of 18
      beta-particles/cm(2) in this case. The presence of cells and medium in a Petri
      dish was found to significantly increase (up to a maximum of 250%) the measured
      number of photons in a narrow band of wavelengths of 340+/-5 nm (i.e. UVA) as
      compared to the signal from an empty control Petri-dish. When coloured growth
      medium was added to the cells, it reduced the measured count rate, while the
      addition of transparent medium in equal volume increased the count rate, compared
      to cells alone. We attribute this to the fact that emission, scattering and
      absorption of light by cells and media are all variables in the experiment. Under
      collimated irradiation conditions, it was observed that increasing cell density
      in medium of fixed volume resulted in a decrease in the observed light output.
      This followed a roughly exponential decline. We suggest that this may be due to
      increased scattering at the cell boundary and absorption of the UV in the cells.
      We conclude that we have measured UVA emitted by cells, cell medium and cell
      substrates as a consequence of their irradiation by low LET beta-particle
      radiation. We suggest that these secondary UV photons could lead to effects in
      non-targetted cells. Some effects that had previously been attributed to a
      chemically mediated "bystander effect" may in fact be due to secondary UV
      emission. Some radiation bystander effect studies may require re-interpretation
      as this phenomenon of UV emission is further investigated. 

PMID- 24298229
TI  - Association of hypertension mortality rates with geographic concentrations of
      chiropractors and medical doctors in the u.s., 2008.
AB  - As concentration (dose) of health care providers increases, health outcomes
      (responses) are expected to be favorable (e.g., decrease in mortality rates).
      Accordingly, this data-driven, ecological study compares hypertension mortality
      rates in the U.S. by state to concentrations of doctors of chiropractic (DC) and
      medical doctors (MD). DC and MD concentrations (per 10,000 population) were
      separately compared to 2008 hypertension death rates using Spearman correlation
      analysis and linear regression (where appropriate). DC concentrations revealed a
      stronger beneficial association with hypertension death rates (r = -0.430, p =
      0.0020) compared to MD concentrations (r = -0.029 with an observed outlier, and r
      = -0.085 without the outlier; both coefficients not statistically significant).
      Linear regression revealed that an average national decrease of approximately one
      hypertension death per 100,000 population (95% CI = -1.4 to -0.4) would be
      expected with an increase of one DC per 10,000 population within the range in
      this study (1.0 to 5.2 DCs per 10,000 population). Since this is an observational
      study, causal inference is not claimed. The study is intended as a first step to
      research having other designs such as case-control. 

PMID- 24298228
TI  - EPA's Stage 2 Disinfection Byproducts Rules (DBPR) and Northern Kentucky Water:
      An Economic and Scientific Review.
AB  - Implementation of EPA's Stage 2 Disinfection Byproducts Rules (DBPR) in Northern
      Kentucky will cause a water rate increase of over 25%. Hence a review was
      undertaken, considering both economics and science in the context of President
      Obama's 2009 scientific integrity directive. The rules purport to avoid up to
      0.49% of new bladder cancers by reducing the levels of DBPs in drinking water - a
      benefit so small that failure to implement will not cause unreasonable risk to
      health (URTH). It suggests at most one Northern Kentucky death avoided over 17
      years for a cost of $136,000,000 ($1700 per household). Even this small benefit
      is probably overstated. EPA finds no "causal link" between DBPs and bladder
      cancer, and EPA acknowledges problems with the epidemiological data used in their
      calculation: the data appear contradictory and inconsistent, may be skewed toward
      "positive" results, and suggest different cancer sites than animal studies. Two
      similar international agencies disagree with EPA's conclusions. The science is
      based on the Linear No Threshold (LNT) dose response model for DBPs, but this may
      not be the correct model. 83% of EPA's epidemiological data show a statistical
      possibility that low levels of DBPs might be beneficial or have no effect. 

PMID- 24298230
TI  - Low Doses of Tetracycline Trigger the E. coli Growth: A Case of Hormetic
      Response.
AB  - Hormesis is a biphasic dose-response relationship, occurring when low
      concentrations of toxic agents elicit apparent improvements. In this work, the
      ability of sub-inhibitory concentrations of Tetracycline to induce hormetic
      response in a model organism was investigated. To this aim a reference strain of
      Escherichia coli, MG1655, was exposed to six decreasing doses of Tetracycline
      (between 0.12 and 0.00375 MUg/ml), much lower than the Minimal Inhibitory
      Concentration (4 MUg/ml). An hormetic increase was observed at the intermediate
      concentrations (0.015-0.03 MUg/ml) of the tested range. The Colony Forming Unit
      number, indeed, rose up to 141% and 121% as compared to the control. At the
      highest (0.12 MUg/ml) and lowest (0.00375 MUg/ml) concentrations a slight
      decrease in CFU number was found. Results demonstrated that, in Escherichia coli,
      low concentrations of Tetracycline bias the bacterial numerical increase through
      a hormetic response; the dose-response curve describing this numerical increase
      is an U-inverted curve. Furthermore, these data confirm that hormesis is common
      to many - if not all - living systems, including bacteria; they underline the
      relevance of a deepened knowledge of both the effects and the possible
      consequences of exposure to low doses of contaminants. 

PMID- 24298231
TI  - Transcript expression patterns illuminate the mechanistic background of hormesis
      in caenorhabditis elegans maupas.
AB  - The animal model Caenorhabditis elegans was employed to study polyphenol- and
      humic substances-induced hormetic changes in lifespan. A detailed insight into
      the underlying mechanism of hormesis was uncovered by applying whole genome DNA
      microarray experimentation over a range of quercetin (Q), tannic acid (TA), and
      humic substances (HuminFeed((r)), HF) concentrations. The transcriptional
      response to all exposures followed a non-linear mode which highlighted
      differential signaling and metabolic pathways. While low Q concentrations
      regulated processes improving the health of the nematodes, higher concentrations
      extended lifespan and modulated substantially the global transcriptional
      response. Over-represented transcripts were notably part of the biotransformation
      process: enhanced catabolism of toxic intermediates possibly contributes to the
      lifespan extension. The regulation of transcription, Dauer entry, and nucleosome
      suggests the presence of distinct exposure dependent differences in transcription
      and signaling pathways. TA- and HF-mediated transcript expression patterns were
      overall similar to each other, but changed across the concentration range
      indicating that their transcriptional dynamics are complex and cannot be
      attributed to a simple adaptive response. In contrast, Q-mediated hormesis was
      well aligned to fit the definition of an adaptive response. Simple molecules are
      more likely to induce an adaptive response than more complex molecules. 

PMID- 24298232
TI  - Comparative Genomics and Systems Biology of Malaria Parasites Plasmodium.
AB  - Malaria is a serious infectious disease that causes over one million deaths
      yearly. It is caused by a group of protozoan parasites in the genus Plasmodium.
      No effective vaccine is currently available and the elevated levels of resistance
      to drugs in use underscore the pressing need for novel antimalarial targets. In
      this review, we survey omics centered developments in Plasmodium biology, which
      have set the stage for a quantum leap in our understanding of the fundamental
      processes of the parasite life cycle and mechanisms of drug resistance and immune
      evasion.

PMID- 24298234
TI  - The ripple pond: enabling spiking networks to see.
AB  - We present the biologically inspired Ripple Pond Network (RPN), a simply
      connected spiking neural network which performs a transformation converting two
      dimensional images to one dimensional temporal patterns (TP) suitable for
      recognition by temporal coding learning and memory networks. The RPN has been
      developed as a hardware solution linking previously implemented neuromorphic
      vision and memory structures such as frameless vision sensors and neuromorphic
      temporal coding spiking neural networks. Working together such systems are
      potentially capable of delivering end-to-end high-speed, low-power and low
      resolution recognition for mobile and autonomous applications where slow, highly
      sophisticated and power hungry signal processing solutions are ineffective. Key
      aspects in the proposed approach include utilizing the spatial properties of
      physically embedded neural networks and propagating waves of activity therein for
      information processing, using dimensional collapse of imagery information into
      amenable TP and the use of asynchronous frames for information binding. 

PMID- 24298233
TI  - Stress and eating: a dual role for bombesin-like peptides.
AB  - The current obesity "epidemic" in the developed world is a major health concern;
      over half of adult Canadians are now classified as overweight or obese. Although
      the reasons for high obesity rates remain unknown, an important factor appears to
      be the role stressors play in overconsumption of food and weight gain. In this
      context, increased stressor exposure and/or perceived stress may influence eating
      behavior and food choices. Stress-induced anorexia is often noted in rats exposed
      to chronic stress (e.g., repeated restraint) and access to standard Chow diet;
      associated reduced consumption and weight loss. However, if a similar stressor
      exposure takes place in the presence of palatable, calorie dense food, rats often
      consume an increase proportion of palatable food relative to Chow, leading to
      weight gain and obesity. In humans, a similar desire to eat palatable or
      "comfort" foods has been noted under stressful situations; it is thought that
      this response may potentially be attributable to stress-buffering properties
      and/or through activation of reward pathways. The complex interplay between
      stress-induced anorexia and stress-induced obesity is discussed in terms of the
      overlapping circuitry and neurochemicals that mediate feeding, stress and reward
      pathways. In particular, this paper draws attention to the bombesin family of
      peptides (BBs) initially shown to regulate food intake and subsequently shown to
      mediate stress response as well. Evidence is presented to support the hypothesis
      that BBs may be involved in stress-induced anorexia under certain conditions, but
      that the same peptides could also be involved in stress-induced obesity. This
      hypothesis is based on the unique distribution of BBs in key cortico-limbic brain
      regions involved in food regulation, reward, incentive salience and
      motivationally driven behavior. 

PMID- 24298236
TI  - Wingless-type family member 3A triggers neuronal polarization via cross
      activation of the insulin-like growth factor-1 receptor pathway.
AB  - Initial axonal elongation is essential for neuronal polarization and requires
      polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3
      kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been
      implied in the regulation of axonal development. It is not known, however, if
      Wnts have any participation in the regulation of initial axonal outgrowth and the
      establishment of neuronal polarity. We used cultured hippocampal neurons and
      growth cone particles (GCPs) isolated from fetal rat brain to show that
      stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote
      neuronal polarization in the absence of IGF-1 or high insulin. We also show that
      Wnt3a triggered a strong activation of IGF-1r, PI3k, and Akt in developmental
      Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation
      were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR)
      experiments show that Wnt3a did not bind specifically to the IGF-1r. Using
      crosslinking and immuno-precipitation experiments, we show that stimulation with
      Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We
      conclude that Wnt3a triggers polarization of neurons via cross-activation of the
      IGF-1r/PI3k pathway upon binding to Fz7. 

PMID- 24298235
TI  - Neuroendocrine regulation of appetitive ingestive behavior.
AB  - Food availability in nature is often irregular, and famine is commonplace.
      Increased motivation to engage in ingestive behaviors increases the chance of
      survival, providing additional potential opportunities for reproduction. Because
      of the advantages conferred by entraining ingestive behavior to environmental
      conditions, neuroendocrine mechanisms regulating the motivation to acquire and
      ingest food have evolved to be responsive to exogenous (i.e., food stored for
      future consumption) and endogenous (i.e., body fat stores) fuel availability.
      Motivated behaviors like eating occur in two phases. The appetitive phase brings
      animals into contact with food (e.g., foraging, food hoarding), and the more
      reflexive consummatory phase results in ingestion (e.g., chewing, swallowing).
      Quantifiable appetitive behaviors are part of the natural ingestive behavioral
      repertoire of species such as hamsters and humans. This review summarizes current
      knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis
      appetitive behavior. We will discuss hormonal regulators of appetitive ingestive
      behaviors, including the orexigenic hormone ghrelin, which potently stimulates
      foraging and food hoarding in Siberian hamsters. This section includes a
      discussion of the hormone leptin, its relation to endogenous fat stores, and its
      role in food deprivation-induced increases in appetitive ingestive behaviors.
      Next, we discuss how hormonal regulators interact with neurotransmitters involved
      in the regulation of ingestive behaviors, such as neuropeptide Y (NPY), agouti
      related protein (AgRP) and alpha-melanocyte stimulating hormone (alpha-MSH), to
      regulate ingestive behavior. Finally, we discuss the potential impact that
      perinatal nutrient availability can have on the neuroendocrine regulation of
      ingestive behavior. Understanding the hormonal mechanisms that connect metabolic
      fuel availability to central appetite regulatory circuits should provide a better
      understanding of the neuroendocrine regulation of the motivation to engage in
      ingestive behavior. 

PMID- 24298237
TI  - MicroRNAs: fundamental regulators of gene expression in major affective disorders
      and suicidal behavior?

PMID- 24298238
TI  - Do we have to reconsider the evolutionary emergence of myelin?

PMID- 24298239
TI  - Metabotropic regulation of extrasynaptic GABAA receptors.
AB  - A large body of work now shows the importance of GABAA receptor-mediated tonic
      inhibition in regulating CNS function. However, outside of pathological
      conditions, there is relatively little evidence that the magnitude of tonic
      inhibition is itself under regulation. Here we review the mechanisms by which
      tonic inhibition is known to be modulated, and outline the potential behavioral
      consequences of this modulation. Specifically, we address the ability of protein
      kinase A and C to phosphorylate the extrasynaptic receptors responsible for the
      tonic GABAA current, and how G-protein coupled receptors can regulate tonic
      inhibition through these effectors. We then speculate about the possible
      functional consequences of regulating the magnitude of the tonic GABAA current. 

PMID- 24298240
TI  - Reevaluation of the role of parallel fiber synapses in delay eyeblink
      conditioning in mice using Cbln1 as a tool.
AB  - The delay eyeblink conditioning (EBC) is a cerebellum-dependent type of
      associative motor learning. However, the exact roles played by the various
      cerebellar synapses, as well as the underlying molecular mechanisms, remain to be
      determined. It is also unclear whether long-term potentiation (LTP) or long-term
      depression (LTD) at parallel fiber (PF)-Purkinje cell (PC) synapses is involved
      in EBC. In this study, to clarify the role of PF synapses in the delay EBC, we
      used mice in which a gene encoding Cbln1 was disrupted (cbln1(-/-) mice), which
      display severe reduction of PF-PC synapses. We showed that delay EBC was impaired
      in cbln1(-/-) mice. Although PF-LTD was impaired, PF-LTP was normally induced in
      cbln1(-/-) mice. A single recombinant Cbln1 injection to the cerebellar cortex in
      vivo completely, though transiently, restored the morphology and function of PF
      PC synapses and delay EBC in cbln1(-/-) mice. Interestingly, the cbln1(-/-) mice
      retained the memory for at least 30 days, after the Cbln1 injection's effect on
      PF synapses had abated. Furthermore, delay EBC memory could be extinguished even
      after the Cbln1 injection's effect were lost. These results indicate that intact
      PF-PC synapses and PF-LTD, not PF-LTP, are necessary to acquire delay EBC in
      mice. In contrast, extracerebellar structures or remaining PF-PC synapses in
      cbln1(-/-) mice may be sufficient for the expression, maintenance, and extinction
      of its memory trace.

PMID- 24298241
TI  - A study on surface slant encoding in V1.
AB  - Inter-ocular differences in spatial frequency occur during binocular viewing of a
      surface slanted in depth. Cortical cells with inter-ocular differences in
      preferred spatial frequency (dif-frequency cells) are expected to detect surfaces
      slanted in depth or vertical surface slant. Using our reaction-diffusion model,
      we obtain receptive fields and responses of simple cells in layer IV in cat V1.
      The dif-frequency cells in the model cortex have tilt in binocular receptive
      field but we show that tilt by itself does not indicate slant selectivity. We
      studied cell responses to binocular combination of spatial frequencies (SFs) by
      varying the SF ratio of the input gratings to the left and right eye in the range
      of 0.35-3. This range of SF ratio corresponds to surface slant variation of -85
      degrees  to 85 degrees . The mean binocular tuning hwhh (half width at half
      height) is 41 degrees . Except for a small number (2.5%) of cells, most dif
      frequency cells respond almost equally well for fronto-parallel surfaces. In the
      literature cells with inter-ocular difference in preferred orientation (IDPO)
      were expected to encode horizontal surface slant. In the model cat V1 mean hwhh
      in binocular orientation tuning curve for cells with IDPO is 39 degrees . The
      wide binocular tuning width in dif-frequency cells and cells with IDPO imply that
      in cat V1 neither dif-frequency cells nor cells with IDPO detect surface slant. 

PMID- 24298242
TI  - Altered frontocingulate activation during aversive interoceptive processing in
      young adults transitioning to problem stimulant use.
AB  - Problems associated with stimulant use have been linked to frontocingulate,
      insular, and thalamic dysfunction during decision making and alterations in
      interoceptive processing. However, little is known about how interoception and
      decision making interact and contribute to dysfunctions that promote the
      transition from recreational drug use to abuse or dependence. Here, we
      investigate brain activation in response to reward, punishment, and uncertainty
      during an aversive interoceptive challenge in current and former stimulant
      (cocaine and amphetamine) users using functional magnetic resonance imaging
      (fMRI). Young adults previously identified as recreational users (n = 184) were
      followed up 3 years later. Of these, 18 individuals progressed to problem
      stimulant use (PSU), whereas 15 desisted stimulant use (DSU). PSU, DSU, and 14
      healthy comparison subjects (CTL) performed a two-choice prediction task at three
      fixed error rates (20% = reward, 50% = uncertainty, 80% = punishment) during
      which they anticipated and experienced episodes of inspiratory breathing load.
      Although groups did not differ in insula activation or subjective breathing load
      ratings, PSU exhibited lower right inferior frontal gyrus (IFG) and bilateral
      anterior cingulate (ACC) activation than DSU and CTL during aversive
      interoceptive processing as well as lower right IFG in response to decision
      making involving uncertainty. However, PSU exhibited greater bilateral IFG
      activation than DSU and CTL while making choices within the context of punishing
      feedback, and both PSU and DSU showed lower thalamic activation during breathing
      load than CTL. Findings suggest that frontocingulate attenuation, reflecting
      reduced resources devoted to goal maintenance and action selection in the
      presence of uncertainty and interoceptive perturbations, may be a biomarker for
      susceptibility to PSU. 

PMID- 24298243
TI  - Maturational delay in ADHD: evidence from CPT.
AB  - While data from behavioral, neuropsychological, and brain studies suggested that
      Attention-Deficit/Hyperactivity Disorder (ADHD) is related to a developmental lag
      that reduces with age, other studies have proposed that ADHD represents a deviant
      brain function. The present study used a cross-sectional approach to examine
      whether ADHD children show a developmental delay in cognitive performance
      measured by continuous performance test (CPT). We thus, compared six age groups
      of ADHD children (N = 559) and their unaffected peers (N = 365), aged 6-11, in
      four parameters of MOXO-CPT performance: Attention, Timing, Hyperactivity and
      Impulsivity. Results have shown that despite improvement in CPT performance with
      age, ADHD children continued to demonstrate impaired performance as compared to
      controls. In most parameters, CPT performance of ADHD children matched that of 1
      3 years younger normal controls, with a delay most prominent in older children.
      However, in the Hyperactivity parameter, ADHD children's performance resembled
      that of much younger healthy children, with almost no evidence for a
      developmental catch up. This study suggests that while some cognitive functions
      develop slower but normally, other functions (e.g., inhibitory control) show a
      different trajectory. 

PMID- 24298244
TI  - Neural activity during free association to conflict-related sentences.
AB  - Psychodynamic conflicts form an important construct to understand the genesis and
      maintenance of mental disorders. Conflict-related themes should therefore provoke
      strong reactions on the behavioral, physiological, and neural level. We
      confronted N = 18 healthy subjects with a vast array of sentences describing
      typical psychodynamic conflict themes in the fMRI scanner and let them associate
      spontaneously in reaction. The overt associations were then analyzed according to
      psychoanalytic theory and the system of operationalized psychodynamic diagnosis
      and used as a genuinely psychodynamic indicator, whether each potentially
      conflict-related sentence actually touched a conflict theme of the individual.
      Behavioral, physiological, and neural reactions were compared between those
      subjects with an "apparent conflict" and those with "absent conflicts." The first
      group reported stronger agreement with the conflict-related sentences, more
      negative valence in reaction, had higher levels of skin conductance reactivity
      and exhibited stronger activation in the anterior cingulate cortex, amongst other
      functions involved in emotion processing and conflict-monitoring. In conjunction,
      we interpret this activity as a possible correlate of subjects' inherent
      reactions and regulatory processes evoked by conflict themes. This study makes a
      point for the fruitfulness of the neuropsychoanalytic endeavor by using free
      association, the classical technique most commonly used in psychoanalysis, to
      investigate aspects of conflict processing in neuroimaging. 

PMID- 24298245
TI  - Deficient fear conditioning in psychopathy as a function of interpersonal and
      affective disturbances.
AB  - The diminished fear reactivity is one of the most valid physiological findings in
      psychopathy research. In a fear conditioning paradigm, with faces as conditioned
      stimulus (CS) and electric shock as unconditioned stimulus (US), we investigated
      a sample of 14 high psychopathic violent offenders. Event related potentials,
      skin conductance responses (SCR) as well as subjective ratings of the CSs were
      collected. This study assessed to which extent the different facets of the
      psychopathy construct contribute to the fear conditioning deficits observed in
      psychopaths. Participants with high scores on the affective facet subscale of the
      Psychopathy Checklist-Revised (PCL-R) showed weaker conditioned fear responses
      and lower N100 amplitudes compared to low scorers. In contrast, high scorers on
      the affective facet rated the CS+ (paired) more negatively than low scorers
      regarding the CS- (unpaired). Regarding the P300, high scores on the
      interpersonal facet were associated with increased amplitudes to the CS+ compared
      to the CS-, while the opposed pattern was found for the antisocial facet. Both,
      the initial and terminal contingent negative variation indicated a divergent
      pattern: participants with pronounced interpersonal deficits, showed increased
      cortical negativity to the CS+ compared to the CS-, whereas a reversed CS+/CS-
      differentiation was found in offenders scoring high on the antisocial facet. The
      present study revealed that deficient fear conditioning in psychopathy was most
      pronounced in offenders with high scores on the affective facet. Event related
      potentials suggest that participants with distinct interpersonal deficits showed
      increased information processing, whereas the antisocial facet was linked to
      decreased attention and interest to the CS+. These data indicate that an approach
      to the facets of psychopathy can help to resolve ambiguous findings in
      psychopathy research and enables a more precise and useful description of this
      disorder. 

PMID- 24298246
TI  - Nutrition as an important mediator of the impact of background variables on
      outcome in middle childhood.
AB  - Adequate nutrition is fundamental to the development of a child's full potential.
      However, the extent to which malnutrition affects developmental and cognitive
      outcomes in the midst of co-occurring risk factors remains largely understudied.
      We sought to establish if the effects of nutritional status varied according to
      diverse background characteristics as well as to compare the relative strength of
      the effects of poor nutritional status on language skills, motor abilities, and
      cognitive functioning at school age. This cross-sectional study was conducted
      among school-age boys and girls resident in Kilifi District in Kenya. We
      hypothesized that the effects of area of residence, school attendance, household
      wealth, age and gender on child outcomes are experienced directly and indirectly
      through child nutritional status. The use of structural equation modeling (SEM)
      allowed the disaggregation of the total effect of the explanatory variables into
      direct effects (effects that go directly from one variable to another) and
      indirect effects. Each of the models tested for the four child outcomes had a
      good fit. However, the effects on verbal memory apart from being weaker than for
      the other outcomes, were not mediated through nutritional status. School
      attendance was the most influential predictor of nutritional status and child
      outcomes. The estimated models demonstrated the continued importance of child
      nutritional status at school-age. 

PMID- 24298247
TI  - Operationalized psychodynamic diagnosis as an instrument to transfer
      psychodynamic constructs into neuroscience.
AB  - This theoretical article makes a contribution to the field of "psychoanalytically
      informed neuroscience". First, central characteristics of psychoanalysis and
      neuroscience are briefly described leading into three epistemic dichotomies.
      Neuroscience versus psychoanalysis display almost opposing methodological
      approaches (reduction vs. expansion), test quality emphases (reliability vs.
      validity) and meaning of results (correlation vs. explanation). The critical
      point is to reach an intermediate level: in neuroscience an adequate position
      integrating both aspects-objective and subjective-of dual-aspect monism, and in
      psychoanalysis the appropriate level for the scientific investigation of its
      central concepts. As a suggestion to reach that level in both fields the system
      of Operationalized Psychodynamic Diagnosis (OPD; OPD Task Force, 2008) is
      presented. Combining aspects of both fields areas, expansion and reduction as
      well as reliability and validity, OPD could be a fruitful tool to transfer
      psychodynamic constructs into neuroscience. The article closes with a short
      description of recent applications of OPD in neuroscience. 

PMID- 24298248
TI  - Neural correlates of uncertain decision making: ERP evidence from the Iowa
      Gambling Task.
AB  - In our daily life, it is very common to make decisions in uncertain situations.
      The Iowa Gambling Task (IGT) has been widely used in laboratory studies because
      of its good simulation of uncertainty in real life activities. The present study
      aimed to examine the neural correlates of uncertain decision making with the IGT.
      Twenty-six university students completed this study. An adapted IGT was
      administered to them, and the EEG data were recorded. The adapted IGT we used
      allowed us to analyze the choice evaluation, response selection, and feedback
      evaluation stages of uncertain decision making within the same paradigm. In the
      choice evaluation stage, the advantageous decks evoked larger P3 amplitude in the
      left hemisphere, while the disadvantageous decks evoked larger P3 in the right
      hemisphere. In the response selection stage, the response of "pass" (the card was
      not turned over; the participants neither won nor lost money) evoked larger
      negativity preceding the response compared to that of "play" (the card was turned
      over; the participant either won or lost money). In the feedback evaluation
      stage, feedback-related negativity (FRN) was only sensitive to the valence
      (win/loss) but not the magnitude (large/small) of the outcome, and P3 was
      sensitive to both the valence and the magnitude of the outcome. These results
      were consistent with the notion that a positive somatic state was represented in
      the left hemisphere and a negative somatic state was represented in the right
      hemisphere. There were also anticipatory ERP effects that guided the
      participants' responses and provided evidence for the somatic marker hypothesis
      with more precise timing. 

PMID- 24298249
TI  - Novel insights in the rehabilitation of neglect.
AB  - Visuospatial neglect due to right hemisphere damage, usually a stroke, is a major
      cause of disability, impairing the ability to perform a whole range of everyday
      life activities. Conventional and long-established methods for the rehabilitation
      of neglect like visual scanning training, optokinetic stimulation, or limb
      activation training have produced positive results, with varying degrees of
      generalization to (un)trained tasks, lasting from several minutes up to various
      months after training. Nevertheless, some promising novel approaches to the
      remediation of left visuospatial neglect have emerged in the last decade. These
      new therapy methods can be broadly classified into four categories. First, non
      invasive brain stimulation techniques by means of transcranial magnetic
      stimulation (TMS) or transcranial direct current stimulation (tDCS), after a
      period of mainly diagnostic utilization, are increasingly applied as
      neurorehabilitative tools. Second, two classes of drugs, dopaminergic and
      noradrenergic, have been investigated for their potential effectiveness in
      rehabilitating neglect. Third, prism adaptation treatment has been shown to
      improve several neglect symptoms consistently, sometimes during longer periods of
      time. Finally, virtual reality technologies hold new opportunities for the
      development of effective training techniques for neglect. They provide realistic,
      rich, and highly controllable training environments. In this paper the degree of
      effectiveness and the evidence gathered to support the therapeutic claims of
      these new approaches is reviewed and discussed. The conclusion is that for all
      these approaches there still is insufficient unbiased evidence to support their
      effectiveness. Further neglect rehabilitation research should focus on the
      maintenance of therapy results over time, on a more functional evaluation of
      treatment effects, on the design and execution of true replication studies and on
      the exploration of optimal combinations of treatments. 

PMID- 24298250
TI  - Region-Specific Slowing of Alpha Oscillations is Associated with Visual
      Perceptual Abilities in Children Born Very Preterm.
AB  - Children born very preterm (<=32 weeks gestational age) without major
      intellectual or neurological impairments often express selective deficits in
      visual-perceptual abilities. The alterations in neurophysiological development
      underlying these problems, however, remain poorly understood. Recent research has
      indicated that spontaneous alpha oscillations are slowed in children born very
      preterm, and that atypical alpha-mediated functional network connectivity may
      underlie selective developmental difficulties in visual-perceptual ability in
      this group. The present study provides the first source-resolved analysis of
      slowing of spontaneous alpha oscillations in very preterm children, indicating
      alterations in a distributed set of brain regions concentrated in areas of
      posterior parietal and inferior temporal regions associated with visual
      perception, as well as prefrontal cortical regions and thalamus. We also uniquely
      demonstrate that slowing of alpha oscillations is associated with selective
      difficulties in visual-perceptual ability in very preterm children. These results
      indicate that region-specific slowing of alpha oscillations contribute to
      selective developmental difficulties prevalent in this population. 

PMID- 24298251
TI  - Propagating synchrony in feed-forward networks.
AB  - Coordinated patterns of precisely timed action potentials (spikes) emerge in a
      variety of neural circuits but their dynamical origin is still not well
      understood. One hypothesis states that synchronous activity propagating through
      feed-forward chains of groups of neurons (synfire chains) may dynamically
      generate such spike patterns. Additionally, synfire chains offer the possibility
      to enable reliable signal transmission. So far, mostly densely connected chains,
      often with all-to-all connectivity between groups, have been theoretically and
      computationally studied. Yet, such prominent feed-forward structures have not
      been observed experimentally. Here we analytically and numerically investigate
      under which conditions diluted feed-forward chains may exhibit synchrony
      propagation. In addition to conventional linear input summation, we study the
      impact of non-linear, non-additive summation accounting for the effect of fast
      dendritic spikes. The non-linearities promote synchronous inputs to generate
      precisely timed spikes. We identify how non-additive coupling relaxes the
      conditions on connectivity such that it enables synchrony propagation at
      connectivities substantially lower than required for linearly coupled chains.
      Although the analytical treatment is based on a simple leaky integrate-and-fire
      neuron model, we show how to generalize our methods to biologically more detailed
      neuron models and verify our results by numerical simulations with, e.g., Hodgkin
      Huxley type neurons. 

PMID- 24298252
TI  - Generalized activity equations for spiking neural network dynamics.
AB  - Much progress has been made in uncovering the computational capabilities of
      spiking neural networks. However, spiking neurons will always be more expensive
      to simulate compared to rate neurons because of the inherent disparity in time
      scales-the spike duration time is much shorter than the inter-spike time, which
      is much shorter than any learning time scale. In numerical analysis, this is a
      classic stiff problem. Spiking neurons are also much more difficult to study
      analytically. One possible approach to making spiking networks more tractable is
      to augment mean field activity models with some information about spiking
      correlations. For example, such a generalized activity model could carry
      information about spiking rates and correlations between spikes self
      consistently. Here, we will show how this can be accomplished by constructing a
      complete formal probabilistic description of the network and then expanding
      around a small parameter such as the inverse of the number of neurons in the
      network. The mean field theory of the system gives a rate-like description. The
      first order terms in the perturbation expansion keep track of covariances. 

PMID- 24298253
TI  - Reaction-diffusion in the NEURON simulator.
AB  - In order to support research on the role of cell biological principles (genomics,
      proteomics, signaling cascades and reaction dynamics) on the dynamics of neuronal
      response in health and disease, NEURON's Reaction-Diffusion (rxd) module in
      Python provides specification and simulation for these dynamics, coupled with the
      electrophysiological dynamics of the cell membrane. Arithmetic operations on
      species and parameters are overloaded, allowing arbitrary reaction formulas to be
      specified using Python syntax. These expressions are then transparently compiled
      into bytecode that uses NumPy for fast vectorized calculations. At each time
      step, rxd combines NEURON's integrators with SciPy's sparse linear algebra
      library. 

PMID- 24298254
TI  - Identification of a self-paced hitting task in freely moving rats based on
      adaptive spike detection from multi-unit M1 cortical signals.
AB  - Invasive brain-computer interfaces (BCIs) may prove to be a useful rehabilitation
      tool for severely disabled patients. Although some systems have shown to work
      well in restricted laboratory settings, their usefulness must be tested in less
      controlled environments. Our objective was to investigate if a specific motor
      task could reliably be detected from multi-unit intra-cortical signals from
      freely moving animals. Four rats were trained to hit a retractable paddle
      (defined as a "hit"). Intra-cortical signals were obtained from electrodes placed
      in the primary motor cortex. First, the signal-to-noise ratio was increased by
      wavelet denoising. Action potentials were then detected using an adaptive
      threshold, counted in three consecutive time intervals and were used as features
      to classify either a "hit" or a "no-hit" (defined as an interval between two
      "hits"). We found that a "hit" could be detected with an accuracy of 75 +/- 6%
      when wavelet denoising was applied whereas the accuracy dropped to 62 +/- 5%
      without prior denoising. We compared our approach with the common daily practice
      in BCI that consists of using a fixed, manually selected threshold for spike
      detection without denoising. The results showed the feasibility of detecting a
      motor task in a less restricted environment than commonly applied within invasive
      BCI research. 

PMID- 24298255
TI  - Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an
      old idea?

PMID- 24298256
TI  - Theranostic quantum dots for crossing blood-brain barrier in vitro and providing
      therapy of HIV-associated encephalopathy.
AB  - The blood-brain barrier (BBB) is a complex physiological checkpoint that
      restricts the free diffusion of circulating molecules from the blood into the
      central nervous system. Delivering of drugs and other active agents across the
      BBB is one of the major technical challenges faced by scientists and medical
      practitioners. Therefore, development of novel methodologies to address this
      challenge holds the key for both the diagnosis and treatment of brain diseases,
      such as HIV-associated encephalopathy. Bioconjugated quantum dots (QDs) are
      excellent fluorescent probes and nano-vectors, being designed to transverse
      across the BBB and visualize drug delivery inside the brain. This paper discusses
      the use of functionalized QDs for crossing the blood-brain barrier and treating
      brain disease. We highlight the guidelines for using in vitro BBB models for
      brain disease studies. The theranostic QDs offers a strategy to significantly
      improve the effective dosages of drugs to transverse across the BBB and orientate
      to the targets inside the brain. 

PMID- 24298257
TI  - NHLBI support of systems biology.
AB  - The National Heart, Lung, and Blood Institute (NHLBI) has recognized the
      importance of the systems biology approach for understanding normal physiology
      and perturbations associated with heart, lung, blood, and sleep diseases and
      disorders. In 2006, NHLBI announced the Exploratory Program in Systems Biology
      program, followed in 2010 by the NHLBI Systems Biology Collaborations program.
      The goal of these programs is to support collaborative teams of investigators in
      using experimental and computational strategies to integrate the component parts
      of biological networks and pathways into computational models that are based
      firmly on and validated using experimental data. These validated models are then
      applied to gain insights into the mechanisms of altered system function in
      disease, to generate novel hypotheses regarding these mechanisms that can be
      tested experimentally, and to then use the results of experiments to refine the
      models. This perspective reviews the history of dedicated systems biology
      programs at NHLBI and reviews some promising directions for future research in
      this area. 

PMID- 24298258
TI  - Cell therapy of periodontium: from animal to human?
AB  - Periodontitis is a chronic inflammatory disease affecting the soft and hard
      tissues supporting the teeth, which often leads to tooth loss. Its significant
      impact on the patient's general health and quality of life point to a need for
      more effective management of this condition. Existing treatments include
      scaling/root planning and surgical approaches but their overall effects are
      relatively modest and restricted in application. The goal of regenerative therapy
      of periodontal defects is to enhance endogenous progenitors and thus promote
      optimal wound healing. Considering that the host or tissue might be defective in
      the periodontitis context, it has been proposed that grafting exogenous stem
      cells would produce new tissues and create a suitable microenvironment for tissue
      regeneration. Thus, cell therapy of periodontium has been assessed in many animal
      models and promising results have been reported. However, the methodological
      diversity of these studies makes the conversion to clinical practice difficult.
      The aim of this review is to highlight the primary requirements to be satisfied
      before the leap to clinical trials can be made. We therefore review cell therapy
      applications for periodontal regeneration in animal models and the concerns to be
      addressed before undertaking human experiments. 

PMID- 24298259
TI  - Increased Ethanol Consumption Following Chronic Psychosocial Stress: Do Oxytocin
      and Baclofen Hold any Therapeutic Promise?

PMID- 24298260
TI  - Disadvantageous Decision-Making as a Predictor of Drop-Out among Cocaine
      Dependent Individuals in Long-Term Residential Treatment.
AB  - BACKGROUND: The treatment of cocaine-dependent individuals (CDI) is substantially
      challenged by high drop-out rates, raising questions regarding contributing
      factors. Recently, a number of studies have highlighted the potential of greater
      focus on the clinical significance of neurocognitive impairments in treatment
      seeking cocaine users. In the present study, we hypothesized that disadvantageous
      decision-making would be one such factor placing CDI at greater risk for
      treatment drop-out. METHODS: In order to explore this hypothesis, the present
      study contrasted baseline performance (at treatment onset) on two validated tasks
      of decision-making, the Iowa Gambling Task (IGT) and the Cambridge Gamble Task
      (CGT) in CDI who completed treatment in a residential Therapeutic Community (TC)
      (N = 66) and those who dropped out of TC prematurely (N = 84). RESULTS: Compared
      to treatment completers, CDI who dropped out of TC prematurely did not establish
      a consistent and advantageous response pattern as the IGT progressed and
      exhibited a poorer ability to choose the most likely outcome on the CGT. There
      were no group differences in betting behavior. CONCLUSION: Our findings suggest
      that neurocognitive rehabilitation of disadvantageous decision-making may have
      clinical benefits in CDI admitted to long-term residential treatment programs.

PMID- 24298261
TI  - Learning to learn to expand freedom in choices.

PMID- 24298262
TI  - Identification, recognition and misidentification syndromes: a psychoanalytical
      perspective.
AB  - Misidentification syndromes are currently often understood as cognitive disorders
      of either the "sense of uniqueness" (Margariti and Kontaxakis, 2006) or the
      recognition of people (Ellis and Lewis, 2001). It is however, necessary to
      consider how a normal "sense of uniqueness" or normal person recognition are
      acquired by normal or neurotic subjects. It will be shown here that the normal
      conditions of cognition can be considered as one of the possible forms of a
      complex structure and not as just a setting for our sense and perception data.
      The consistency and the permanency of the body image in neurosis is what permits
      the recognition of other people and ourselves as unique beings. This consistency
      and permanency are related to object repression, as shown by neurological
      disorders of body image (somatoparaphrenia), which cause the object to come to
      the foreground in the patient's words (Thibierge and Morin, 2010). In
      misidentification syndromes, as in other psychotic syndromes, one can also
      observe damage to the specular image as well as an absence of object repression.
      This leads us to question whether, in the psychiatric disorders related to a
      damaged specular image, disorders of cognition can be studied and managed using
      the same methods as for neurotic patients. 

PMID- 24298263
TI  - Tempting food words activate eating simulations.
AB  - This study shows that tempting food words activate simulations of eating the
      food, including simulations of the taste and texture of the food, simulations of
      eating situations, and simulations of hedonic enjoyment. In a feature listing
      task, participants generated features that are typically true of four tempting
      foods (e.g., chips) and four neutral foods (e.g., rice). The resulting features
      were coded as features of eating simulations if they referred to the taste,
      texture, and temperature of the food (e.g., "crunchy"; "sticky"), to situations
      of eating the food (e.g., "movie"; "good for Wok dishes"), and to the hedonic
      experience when eating the food (e.g., "tasty"). Based on the grounded cognition
      perspective, it was predicted that tempting foods are more likely to be
      represented in terms of actually eating them, so that participants would list
      more features referring to eating simulations for tempting than for neutral
      foods. Confirming this hypothesis, results showed that eating simulation features
      constituted 53% of the features for tempting food, and 26% of the features for
      neutral food. Visual features, in contrast, were mentioned more often for neutral
      foods (45%) than for tempting foods (19%). Exploratory analyses revealed that the
      proportion of eating simulation features for tempting foods was positively
      correlated with perceived attractiveness of the foods, and negatively with
      participants' dieting concerns, suggesting that eating simulations may depend on
      individuals' goals with regard to eating. These findings are discussed with
      regard to their implications for understanding the processes guiding eating
      behavior, and for interventions designed to reduce the consumption of attractive,
      unhealthy food. 

PMID- 24298264
TI  - Stroop interference in a delayed match-to-sample task: evidence for semantic
      competition.
AB  - Discussions of the source of the Stroop interference effect continue to pervade
      the literature. Semantic competition posits that interference results from
      competing semantic activation of word and color dimensions of the stimulus prior
      to response selection. Response competition posits that interference results from
      competing responses for articulating the word dimension vs. the color dimension
      at the time of response selection. We embedded Stroop stimuli into a delayed
      match-to-sample (DMTS) task in an attempt to test semantic and response
      competition accounts of the interference effect. Participants viewed a sample
      color word in black or colored fonts that were congruent or incongruent with
      respect to the color word itself. After a 5 s delay, participants were presented
      with two targets (i.e., a match and a foil) and were instructed to select the
      correct match. We probed each dimension independently during target presentations
      via color targets (i.e., two colors) or word targets (i.e., two words) and
      manipulated whether the semantic content of the foil was related to the semantic
      content of the irrelevant sample dimension (e.g., word sample "red" in blue font
      with the word "red" as the match and the word "blue" as the foil). We provide
      evidence for Stroop interference such that response times (RTs) increased for
      incongruent trials even in the presence of a response option with semantic
      content unrelated to the semantic content of the irrelevant sample dimension.
      Accuracy also deteriorated during the related foil trials. A follow-up experiment
      with a 10 s delay between sample and targets replicated the results. Results
      appear to provide converging evidence for Stroop interference in a DMTS task in a
      manner that is consistent with an explanation based upon semantic competition and
      inconsistent with an explanation based upon response competition. 

PMID- 24298265
TI  - A New Tool for Investigating the Functional Testing of the VOR.
AB  - Peripheral vestibular function may be tested quantitatively, by measuring the
      gain of the angular vestibulo-ocular reflex (aVOR), or functionally, by assessing
      how well the aVOR performs with respect to its goal of stabilizing gaze in space
      and thus allow to acquire visual information during the head movement. In recent
      years, several groups have developed clinical and quantitative approaches to
      functional testing of the vestibular system based on the ability to identify an
      optotype briefly displayed on screen during head rotations. Although the proposed
      techniques differ in terms of the parameters controlling the testing paradigm, no
      study has thus far dealt with understanding the role of such choices in
      determining the effectiveness and reliability of the testing approach. Moreover,
      recent work has shown that peripheral vestibular patients may produce corrective
      saccades during the head movement (covert saccades), yet the role of these eye
      movements toward reading ability during head rotations is not yet understood.
      Finally, no study has thus far dealt with measuring the true performance of their
      experimental setups, which is nonetheless likely to be crucial information for
      understanding the effectiveness of functional testing approaches. Thus we propose
      a new software and hardware research tool allowing the combined measurement of
      eye and head movements, together with the timing of the optotype on screen,
      during functional testing of the vestibulo-ocular reflex (VOR) based on the Head
      Impulse Test. The goal of such tool is therefore that of allowing functional
      testing of the VOR while collecting the experimental data necessary to
      understand, for instance, (a) the effectiveness of the covert saccades strategy
      toward image stabilization, (b) which experimental parameters are crucial for
      optimizing the diagnostic power of the functional testing approach, and (c) which
      conditions lead to a successful reading or an error trial. 

PMID- 24298266
TI  - Amygdala Enlargement in Patients with Mesial Temporal Lobe Epilepsy without
      Hippocampal Sclerosis.
AB  - PURPOSE: Patients with mesial temporal lobe epilepsy (MTLE) without MRI
      abnormalities (MTLE-NL) represent a challenge for definition of underlying
      pathology and for presurgical evaluation. In a recent study we observed
      significant amygdala enlargement (AE) in 14% of MTLE patients with MRI signs of
      hippocampal sclerosis. Areas of gray matter volume (GMV) increase could represent
      structural abnormalities related to the epileptogenic zone or part of a
      developmental abnormality. Our objective was to look for undetected areas of
      increased GMV in MTLE-NL using post processing MRI techniques to better
      understand the pathophysiology of this condition. METHODS: We evaluated 66
      patients with MTLE-NL on visual analysis and 82 controls. Voxel-based morphometry
      (VBM) group analysis was performed with VBM8/SPM8 looking for areas of increased
      GMV. We then performed automatic amygdala volumetry using FreeSurfer software and
      T2 relaxometry to confirm VBM findings. RESULTS: Voxel-based morphometry group
      analysis demonstrated increased amygdala volume in the MTLE-NL group compared to
      controls. Individual volumetric analysis confirmed AE in eight (12%) patients.
      Overall, from all patients with AE and defined epileptic focus, four (57%) had
      the predominant increased volume ipsilateral to the epileptic focus. These
      results were cross-validated by a secondary VBM analysis including subgroups of
      patients according to the volumetric data. T2 relaxometry demonstrated no
      amygdala hyperintense signal in any individual with significant AE. There were no
      clinical differences between patients with and without AE. DISCUSSION: This
      exploratory study demonstrates the occurrence of AE in 12% of patients with MTLE
      NL. This finding supports the hypothesis that there might be a subgroup of
      patients with MTLE-NL in which the enlarged amygdala could be related to the
      epileptogenic process. Further studies are necessary but this finding could be of
      great importance in the understanding of MTLE-NL.

PMID- 24298268
TI  - Remodeling of energy metabolism and absence of electrophysiological changes in
      the heart of obese hyperleptinemic mice. New insights into the pleiotropic role
      of leptin.
AB  - Dietary treatment with high-fat diets (HFD) triggers diabetes and
      hyperleptinemia, concomitantly with a partial state of leptin resistance that
      affects hepatic and adipose tissue but not the heart. In this context,
      characterized by widespread steatosis, cardiac lipid content remains unchanged.
      As previously reported, HFD-evoked hyperleptinemia could be a pivotal element
      contributing to increase fatty-acid (FA) metabolism in the heart and to prevent
      cardiac steatosis. This metabolic adaptation might theoretically reduce energy
      efficiency in cardiomyocytes and lead to cardiac electrophysiological remodeling.
      Therefore the aim of the current study has been to investigate the impact of long
      term HFD on cardiac metabolism and electrophysiological properties of the
      principal ionic currents responsible of the action potential duration in mouse
      cardiomyocytes. Male C57BL/6J mice were fed a control (10 kcal% from fat) or HFD
      (45 kcal% from fat) during 32 weeks. Quantification of enzymatic activities
      regulating mitochondrial uptake of pyruvate and FA showed an increase of both
      carnitine-palmitoyltransferase and citrate synthase activities together with a
      decrease of lactate dehydrogenase and pyruvate dehydrogenase activities.
      Increased expression of uncoupling protein-3, Mn-, and Cu/Zn-superoxide
      dismutases and catalase were also detected. Total glutathione/oxidized
      glutathione ratios were unaffected by HFD. These data suggest that HFD triggers
      adaptive mechanisms aimed at (i) facilitating FA catabolism, and (ii) preventing
      oxidative stress. All these changes did not affect the duration of action
      potentials in cardiomyocytes and only slightly modified electrocardiographic
      parameters. 

PMID- 24298269
TI  - Effects of an Early Experience Involving Training in a T-Maze Under either Denial
      or Receipt of Expected Reward through Maternal Contact.
AB  - The mother is the most salient stimulus for the developing pups and a number of
      early experience models employ manipulation of the mother-infant interaction. We
      have developed a new model which in addition to changes in maternal behavior
      includes a learning component on the part of the pups. More specifically, pups
      were trained in a T-maze and either received (RER rats) or were denied (DER) the
      reward of maternal contact, during postnatal days 10-13. Pups of both
      experimental groups learn the T-maze, but the RER do so more efficiently
      utilizing a procedural-type of learning and memory with activation of the dorsal
      basal ganglia. On the other hand, the DER experience leads to activation of the
      hippocampus, prefrontal cortex, and amygdala in the pups. In adulthood, male DER
      animals exhibit better mnemonic abilities in the Morris water maze and higher
      activation of the hippocampus, while they have decreased brain serotonergic
      activity, exhibit a depressive-like phenotype and proactive aggressive behavior
      in the resident-intruder test. While male RER animals assume a reactive coping
      style in this test, and showed increased freezing during both contextual and cued
      memory recall following fear conditioning. 

PMID- 24298267
TI  - A Role for the Brain RAS in Alzheimer's and Parkinson's Diseases.
AB  - The brain renin-angiotensin system (RAS) has available the necessary functional
      components to produce the active ligands angiotensins II (AngII), angiotensin
      III, angiotensins (IV), angiotensin (1-7), and angiotensin (3-7). These ligands
      interact with several receptor proteins including AT1, AT2, AT4, and Mas
      distributed within the central and peripheral nervous systems as well as local
      RASs in several organs. This review first describes the enzymatic pathways in
      place to synthesize these ligands and the binding characteristics of these
      angiotensin receptor subtypes. We next discuss current hypotheses to explain the
      disorders of Alzheimer's disease (AD) and Parkinson's disease (PD), as well as
      research efforts focused on the use of angiotensin converting enzyme (ACE)
      inhibitors and angiotensin receptor blockers (ARBs), in their treatment. ACE
      inhibitors and ARBs are showing promise in the treatment of several
      neurodegenerative pathologies; however, there is a need for the development of
      analogs capable of penetrating the blood-brain barrier and acting as agonists or
      antagonists at these receptor sites. AngII and AngIV have been shown to play
      opposing roles regarding memory acquisition and consolidation in animal models.
      We discuss the development of efficacious AngIV analogs in the treatment of
      animal models of AD and PD. These AngIV analogs act via the AT4 receptor subtype
      which may coincide with the hepatocyte growth factor/c-Met receptor system.
      Finally, future research directions are described concerning new approaches to
      the treatment of these two neurological diseases. 

PMID- 24298270
TI  - Reduced vancomycin susceptibility in porcine ST9 MRSA isolates.
AB  - Porcine strains of livestock-associated methicillin resistant Staphylococcus
      aureus (LA-MRSA) have been recognized in many countries and have been shown to be
      able to cause human infection. Resistance to non-beta lactam antibiotics has been
      reported but non-susceptibility to vancomycin, which is known to occur in human
      MRSA, has so far not been observed in LA-MRSA. Such resistance is typically
      fairly low level involving changes in the cell wall thickness. The development of
      resistance is usually preceded by presence of a sub-population having an
      increased MIC, which is selected for by exposure to vancomycin. This study
      investigated vancomycin susceptibility of one hundred porcine MRSA isolates using
      three MIC methods including spiral gradient endpoint (SGE) technique which allows
      visualization of more resistant sub-populations. SGE revealed 16 strains with an
      MIC above 2.0 mg/L, of which 14 were determined to have MIC 4 mg/L by agar
      dilution (AD). SGE revealed a further two isolates with MIC < 2 mg/L had a sub
      population >2 mg/L. In addition, trailing endpoints not reaching resistance were
      present in 26 isolates with MIC < 2 mg/L. Sequencing of the genes of the
      VraSR/GraSR two component systems of ten of the resistant strains for comparison
      with susceptible strains revealed changes, including the presence of stop codons,
      in vraS and graR, but these were not consistent in all isolates. Other genetic
      changes may contribute to vancomycin non-susceptibility and require
      investigation. As failure to respond to treatment has been reported in clinical
      isolates with MIC > 1.5 mg/L, the presence of vancomycin non-susceptibility in
      porcine isolates is of concern and further monitoring of LA-MRSA is essential. 

PMID- 24298271
TI  - New perspectives on ancient granulomas.

PMID- 24298272
TI  - Models of somatic hypermutation targeting and substitution based on synonymous
      mutations from high-throughput immunoglobulin sequencing data.
AB  - Analyses of somatic hypermutation (SHM) patterns in B cell immunoglobulin (Ig)
      sequences contribute to our basic understanding of adaptive immunity, and have
      broad applications not only for understanding the immune response to pathogens,
      but also to determining the role of SHM in autoimmunity and B cell cancers.
      Although stochastic, SHM displays intrinsic biases that can confound statistical
      analysis, especially when combined with the particular codon usage and base
      composition in Ig sequences. Analysis of B cell clonal expansion,
      diversification, and selection processes thus critically depends on an accurate
      background model for SHM micro-sequence targeting (i.e., hot/cold-spots) and
      nucleotide substitution. Existing models are based on small numbers of
      sequences/mutations, in part because they depend on data from non-coding regions
      or non-functional sequences to remove the confounding influences of selection.
      Here, we combine high-throughput Ig sequencing with new computational analysis
      methods to produce improved models of SHM targeting and substitution that are
      based only on synonymous mutations, and are thus independent of selection. The
      resulting "S5F" models are based on 806,860 Synonymous mutations in 5-mer motifs
      from 1,145,182 Functional sequences and account for dependencies on the adjacent
      four nucleotides (two bases upstream and downstream of the mutation). The
      estimated profiles can explain almost half of the variance in observed mutation
      patterns, and clearly show that both mutation targeting and substitution are
      significantly influenced by neighboring bases. While mutability and substitution
      profiles were highly conserved across individuals, the variability across motifs
      was found to be much larger than previously estimated. The model and method
      source code are made available at http://clip.med.yale.edu/SHM. 

PMID- 24298274
TI  - CD40-Mediated Activation of the NF-kappaB2 Pathway.
AB  - CD40 is a critical stimulatory receptor on antigen-presenting cells of the immune
      system. CD40-mediated activation of B cells is particularly important for normal
      humoral immune function. Engagement of CD40 by its ligand, CD154, on the surface
      of activated T cells initiates a variety of signals in B cells including the
      activation of MAP kinases and NF-kappaB. The transcriptional regulator NF-kappaB
      is in reality a family of factors that can promote B cell activation,
      differentiation, and proliferation. Complex - and only partially understood -
      biochemical mechanisms allow CD40 to trigger two distinct NF-kappaB activation
      pathways resulting in the activation of canonical (NF-kappaB1) and non-canonical
      (NF-kappaB2) NF-kappaB. This brief review provides a summary of mechanisms
      responsible for activation of the latter, which appears to be particularly
      important for enhancing the viability of B cells at various stages in their life
      cycle and may also contribute to the development of B cell malignancies. CD40 is
      also expressed by various cell types in addition to B cells, including T cells,
      macrophages, dendritic cells, as well as certain non-hematopoietic cells. Here
      too, while perhaps less extensively studied than in B cells, the CD40-mediated
      activation of NF-kappaB2 also appears to have important roles in cellular
      physiology. 

PMID- 24298273
TI  - IgM Repertoire Biodiversity is Reduced in HIV-1 Infection and Systemic Lupus
      Erythematosus.
AB  - BACKGROUND: HIV-1 infection or systemic lupus erythematosus (SLE) disrupt B cell
      homeostasis, reduce memory B cells, and impair function of IgG and IgM
      antibodies. OBJECTIVE: To determine how disturbances in B cell populations
      producing polyclonal antibodies relate to the IgM repertoire, the IgM
      transcriptome in health and disease was explored at the complementarity
      determining region 3 (CDRH3) sequence level. METHODS: 454-deep pyrosequencing in
      combination with a novel analysis pipeline was applied to define populations of
      IGHM CDRH3 sequences based on absence or presence of somatic hypermutations (SHM)
      in peripheral blood B cells. RESULTS: HIV or SLE subjects have reduced
      biodiversity within their IGHM transcriptome compared to healthy subjects, mainly
      due to a significant decrease in the number of unique combinations of alleles,
      although recombination machinery was intact. While major differences between
      sequences without or with SHM occurred among all groups, IGHD and IGHJ allele
      use, CDRH3 length distribution, or generation of SHM were similar among study
      cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV
      infected individuals. All subjects had a low frequency of allelic combinations
      within the IGHM repertoire similar to known broadly neutralizing HIV-1
      antibodies. CONCLUSION: Polyclonal expansion would decrease overall IgM
      biodiversity independent of other mechanisms for development of the B cell
      repertoire. Applying deep sequencing as a strategy to follow development of the
      IgM repertoire in health and disease provides a novel molecular assessment of
      multiple points along the B cell differentiation pathway that is highly sensitive
      for detecting perturbations within the repertoire at the population level.

PMID- 24298275
TI  - Current status and proposed roles for nitric oxide as a key mediator of the
      effects of extracellular nucleotides on plant growth.
AB  - Recent data indicate that nucleotides are released into the extracellular matrix
      during plant cell growth, and that these extracellular nucleotides induce
      signaling changes that can, in a dose-dependent manner, increase or decrease the
      cell growth. After activation of a presumed receptor, the earliest signaling
      change induced by extracellular nucleotides is an increase in the concentration
      of cytosolic Ca(2+), but rapidly following this change is an increase in the
      cellular level of nitric oxide (NO). In Arabidopsis, mutants deficient in nitrate
      reductase activity (nia1nia2) have drastically reduced nitric oxide production
      and cannot transduce the effects of applied nucleotides into growth changes. Both
      increased levels of extracellular nucleotides and increased NO production inhibit
      auxin transport and inhibit growth, and these effects are potentially due to
      disruption of the localization and/or function of auxin transport facilitators.
      However, because NO- and auxin-induced signaling pathways can intersect at
      multiple points, there may be diverse ways by which the induction of NO by
      extracellular ATP could modulate auxin signaling and thus influence growth. This
      review will discuss these optional mechanisms and suggest possible regulatory
      routes based on current experimental data and predictive computational analyses. 

PMID- 24298276
TI  - A phosphorylation map of the photosystem II supercomplex C2S2M2.

PMID- 24298277
TI  - Utility of Synechocystis sp. PCC 6803 glutaredoxin A as a platform to study high
      resolution mutagenesis of proteins.
AB  - Glutaredoxin from the cyanobacterium Synechocystis sp. PCC 6803 is a small
      protein, containing only 88 amino acids, that participates in a large number of
      redox reactions, serving both as an electron donor for enzyme-catalyzed
      reductions and as a regulator of diverse metabolic pathways. The crystal
      structures of glutaredoxins from several species have been solved, including the
      glutaredoxin A isoform from the cyanobacterium Synechocystis sp. PCC 6803. We
      have utilized the small size of Synechocystis glutaredoxin A and its propensity
      to form protein crystals that diffract to high resolution to explore a long
      standing question in biochemistry; i.e., what are the effects of mutations on
      protein structure and function? Taking advantage of these properties, we have
      initiated a long-term educational project that would examine the structural and
      biochemical changes in glutaredoxin as a function of single-point mutational
      replacements. Here, we report some of the mutational effects that we have
      observed to date. 

PMID- 24298278
TI  - Semi-supervised spectral clustering with application to detect population
      stratification.
AB  - In genetic association studies, unaccounted population stratification can cause
      spurious associations in a discovery process of identifying disease-associated
      genetic markers. In such a situation, prior information is often available for
      some subjects' population identities. To leverage the additional information, we
      propose a semi-supervised clustering approach for detecting population
      stratification. This approach maintains the advantages of spectral clustering,
      while is integrated with the additional identity information, leading to sharper
      clustering performance. To demonstrate utility of our approach, we analyze a
      whole-genome sequencing dataset from the 1000 Genomes Project, consisting of the
      genotypes of 607 individuals sampled from three continental groups involving 10
      subpopulations. This is compared against a semi-supervised spectral clustering
      method, in addition to a spectral clustering method, with the known subpopulation
      information by the Rand index and an adjusted Rand (ARand) index. The numerical
      results suggest that the proposed method outperforms its competitors in detecting
      population stratification. 

PMID- 24298279
TI  - Evaluation of calling algorithms for array-CGH.
AB  - Copy number variation (CNV) detection has become an integral part many of genetic
      studies and new technologies promise to revolutionize our ability to detect and
      link them to disease. However, recent studies highlight discrepancies in the
      genome wide CNV profile when measured by different technologies and even by the
      same technology. Furthermore, the change point algorithms used to call CNVs can
      have substantial disagreement on the same data set. We focus this article on
      comparative genomic hybridization (CGH) arrays because this platform lends itself
      well to accurate statistical modeling. We describe some newer methodological
      developments in local statistics that are well suited for CNV detection and
      calling on CGH arrays. Then we use both simulation studies and public data to
      compare these new local methods with the global methods that currently dominate
      literature. These results offer suggestions for choosing a particular method and
      provide insight to the lack of reproducibility that has been seen in the field so
      far. 

PMID- 24298281
TI  - Endoscopy-MR Image Fusion for Image Guided Procedures.
AB  - Minimally invasive endoscope based abdominal procedures provide potential
      advantages over conventional open surgery such as reduced trauma, shorter
      hospital stay, and quick recovery. One major limitation of using this technique
      is the narrow view of the endoscope and the lack of proper 3D context of the
      surgical site. In this paper, we propose a rapid and accurate method to align
      intraoperative stereo endoscopic images of the surgical site with preoperative
      Magnetic Resonance (MR) images. Gridline light pattern is projected on the
      surgical site to facilitate the registration. The purpose of this surface-based
      registration is to provide 3D context of the surgical site to the endoscopic
      view. We have validated the proposed method on a liver phantom and achieved the
      surface registration error of 0.76 +/- 0.11 mm. 

PMID- 24298280
TI  - A systematic experimental evaluation of microRNA markers of human bladder cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that regulate gene
      expression. They are aberrantly expressed in many human cancers and are potential
      therapeutic targets and molecular biomarkers. METHODS: In this study, we for the
      first time validated the reported data on the entire set of published
      differential miRNAs (102 in total) through a series of transcriptome-wide
      experiments. We have conducted genome-wide miRNA profiling in 17 urothelial
      carcinoma bladder tissues and in nine normal urothelial mucosa samples using
      three methods: (1) An Illumina HT-12 microarray hybridization (MA) analysis (2) a
      suppression-subtractive hybridization (SSH) assay followed by deep sequencing
      (DS) and (3) DS alone. RESULTS: We show that DS data correlate with previously
      published information in 87% of cases, whereas MA and SSH data have far smaller
      correlations with the published information (6 and 9% of cases, respectively).
      qRT-PCR tests confirmed reliability of the DS data. CONCLUSIONS: Based on our
      data, MA and SSH data appear to be inadequate for studying differential miRNA
      expression in the bladder. IMPACT: We report the first comprehensive validated
      database of miRNA markers of human bladder cancer.

PMID- 24298282
TI  - Use of radiofrequency ablation in benign thyroid nodules: a literature review and
      updates.
AB  - Successful thermal ablation using radiofrequency has been reported in various
      tumors including liver or kidney tumors. Nonsurgical minimally invasive ablative
      therapy such as radiofrequency ablation (RFA) has been reported to be a safe and
      efficient treatment option in managing symptomatic cold thyroid nodules or
      hyperfunctioning thyroid nodules. Pressure and cosmetic symptoms have been shown
      to be significantly improved both in the short and long terms after RFA. For
      hyperfunctioning thyroid nodules, RFA is indicated for whom surgery or
      radioiodine are not indicated or ineffective or for those who refuse surgery or
      radio-iodine. Improvement of thyroid function with decreased need for antithyroid
      medications has been reported. Complication rate is relatively low. By reviewing
      the current literature, we reported its efficacy and complications and compared
      the efficacy of RFA relative to other ablative options such as ethanol ablation
      and laser ablation. 

PMID- 24298284
TI  - Efficient Degradation of Feather by Keratinase Producing Bacillus sp.
AB  - Keratinase producing microorganisms are being increasingly utilized for
      degradation and recycling of poultry feather waste. Two native strains BF11
      (Bacillus subtilis) and BF21 (Bacillus cereus) degrading keratin completely were
      characterized. The native strains produced more than 10 KU/mL of enzyme. Strain
      improvement resulted in isolation of MBF11 and MBF21 from BF11 and BF21 isolates,
      respectively. Optimization of nutritional and physical parameters of these MBF
      isolates at laboratory scale increased the overall keratinase activity by 50-fold
      resulting in a yield of 518-520 KU/mL. Fermentation media designed with starch as
      carbon source and soya bean meal as nitrogen source supported high levels of
      enzyme production. The optimum conditions for enzyme production were determined
      to be pH 8.5 and temperatures of 45-55 degrees C for MBF11 and 37 degrees C for
      MBF21, respectively. Culture filtrate showed a significant increase in the
      amounts of cysteine, cystine, methionine, and total free amino acids during the
      fermentation period. The ratio of organic sulphur concentration was also
      considerably higher than that of the inorganic sulphate in the culture filtrate
      suggesting the hydrolysis of disulphide by the isolates. 

PMID- 24298283
TI  - Irisin, two years later.
AB  - In January 2012, Bostrom and colleagues identified a new muscle tissue secreted
      peptide, which they named irisin, to highlight its role as a messenger that comes
      from skeletal muscle to other parts of the body. Irisin is a cleaved and secreted
      fragment of FNDC5 (also known as FRCP2 and PeP), a member of fibronectin type III
      repeat containing gene family. Major interest in this protein arose because of
      its great therapeutic potential in diabetes and perhaps also therapy for obesity.
      Here we review the most important aspects of irisin's action and discuss its
      involvement in energy and metabolic homeostasis and whether the beneficial
      effects of exercise in these disease states could be mediated by this protein. In
      addition the effects of irisin at the central nervous system (CNS) are
      highlighted. It is concluded that although current and upcoming research on
      irisin is very promising it is still necessary to deepen in several aspects in
      order to clarify its full potential as a meaningful drug target in human disease
      states. 

PMID- 24298285
TI  - Quantifying the extruded bacteria following use of two rotary instrumentation
      systems.
AB  - INTRODUCTION: All instrumentation techniques have been reported to be associated
      with extrusion of infected debris. The aim of this study was to evaluate the
      number of bacteria extruded apically from extracted teeth ex vivo after canal
      instrumentation using the two engine-driven techniques utilizing nickel-titanium
      instruments (Flex Master and Mtwo). MATERIALS AND METHODS: Seventy extracted
      maxillary central incisor teeth were used. Access cavities were prepared and root
      canals were then contaminated with a suspension of Enterococcus faecalis and
      dried. The contaminated roots were divided into two experimental groups of 30
      teeth each and one control group of 10 teeth. Group 1, Flex Master; Group2, Mtwo;
      Group 3, control group: no instrumentation was attempted. Bacteria extruded from
      the apical foramen during instrumentation were collected into vials. The
      microbiological samples from the vials were incubated in culture media for 24 h.
      Colonies of bacteria were counted and the results were given as number of colony
      forming units. The obtained data were analyzed using the Kruskal-Wallis one-way
      analysis of variance and Mann-Whitney U-tests, with alpha = 0.05 as the level for
      statistical significance. RESULTS: Findings showed that there was no significant
      difference as to the number of extruded bacteria between two engine-driven
      systems (P>0.05). CONCLUSION: Both engine-driven Nickel-Titanium systems extruded
      bacteria through the apical foramen.

PMID- 24298286
TI  - The Long-Term Effect of Saline and Phosphate Buffer Solution on MTA: An SEM and
      EPMA Investigation.

PMID- 24298287
TI  - Evaluation of Adhesion and Morphology of Human Osteoblasts to White MTA and
      Portland Cement.
AB  - INTRODUCTION: Osteoblasts and periodontal ligament cells are major cells for
      wound healing after root end resection. The interaction of osteoblasts with
      filling materials could play a critical role in healing of surgical lesion.
      Adhesion and spreading of cells on material surface are the initial phase for
      cellular function. The purpose of the present study was the evaluation of
      morphology and attachment of human osteoblasts in present of white MTA, Portland
      cement (PC) and IRM as root end filling and perforation repair materials.
      MATERIALS AND METHODS: The human osteoblasts (MG-63 cell line) were prepared from
      Iranian Pasteur Institute; Cellular Bank, were grown in RPMI 1640 medium. The
      testing materials were mixed according to the manufacture's instruction, inserted
      in to the wells of 24-well flat-bottomed plate, and condensed to disk of 1mm
      thickness and 1*1mm diameter. Cells were added to the materials after two weeks.
      During 1,3,7 days intervals, the disk of materials along with cells were grown on
      their surface, examined by a scanning electron microscope (SEM). We used of IRM
      as negative group. RESULTS: Results showed that after 7 days many of osteoblasts
      were attached on the surface of white MTA and PC and appeared partially round or
      flat. The cells appeared round with no attachment and spreading in conjunction
      with IRM. CONCLUSION: The results indicate that human osteoblasts have a
      favorable response to white MTA and Portland cement compared with IRM.

PMID- 24298288
TI  - Cytotoxicity Evaluation of Proroot MTA, Root MTA and Portland Cement on Human
      Gingival Fibroblasts.
AB  - INTRODUCTION: The aim of this study was to compare the cytotoxicity of ProRoot
      MTA (PMTA), Root MTA (RMTA) and Portland cement (PC) on human gingival
      fibroblasts (HGFs). MATERIALS AND METHODS: The extracts of the test materials
      were placed close to human gingival fibroblasts (HGFs) within 96-well plates.
      Cellular viability was assessed using MTT assay in different intervals (freshly
      mixed, 4, 24, and 168 hours after mixing). The data were analyzed using the One
      way ANOVA and Tukey's test at 95% significance level. RESULTS: It was indicated
      that there was not a significant difference in cytotoxicity of test materials
      (p>0.05). In addition, there was not a statistically significant difference
      between different time intervals within each group (p>0.05). CONCLUSION: PMTA,
      RMTA and PC showed comparative biocompatibility while evaluated in-vitro.

PMID- 24298289
TI  - A scanning electron microscopic comparison of the cleaning efficacy of endodontic
      irrigants.
AB  - INTRODUCTION: The aim of this study was to compare the cleaning efficacy of three
      irrigants used during and after instrumentation. MATERIALS AND METHODS: Eighty
      four single rooted human teeth were randomly divided into 7 groups, 12 cases
      each, and canals were instrumented with Mtwo rotary systems. 5.25% sodium
      hypochlorite, Smear Clear and 17% EDTA were used for irrigation of the canal
      during and/ or after instrumentation. After completion of instrumentation, all
      canals were dried with paper points and prepared to examine by scanning electron
      microscope. All SEM photomicrographs were scored at the coronal, middle and
      apical thirds of canals in each group. The data were statistically analyzed using
      Mann-Whitney and Kruskal-Wallis tests. RESULTS: In the group irrigated with Smear
      Clear alone, the coronal thirds of the canals were significantly cleaner than
      middle thirds (P=0.013) and apical thirds (P=0.028). There were less smear layer
      in the coronal thirds compared to apical thirds (P=0.047) in the group irrigated
      with Smear Clear and NaOCl alternately .There were significantly more smear layer
      in the apical thirds compared to coronal thirds (P<0.001) and middle thirds
      (P=0.007) in the group that Smear Clear and NaOCl were used as final irrigations.
      There was not any significant difference between three-thirds of the canals in
      other groups. Comparison of the all groups showed a statistically significant
      difference (P<0.001) in the amount of debris and smear layer remaining at all
      three levels of the canals. CONCLUSION: The findings of this study suggested that
      a final rinsing by combination of a chelating agent like EDTA or Smear Clear and
      NaOCl is necessary to obtain favorable clean wall of root canals.

PMID- 24298290
TI  - Evaluation of antimicrobial effect of MTA, calcium hydroxide, and CEM cement.
AB  - INTRODUCTION: The antibacterial effects of calcium hydroxide (CH), mineral
      trioxide aggregate (MTA), and calcium enriched mixture (CEM) cement against
      various spp. of microorganisms were assessed in-vitro using agar diffusion test.
      MATERIALS AND METHODS: A base layer of Petri plates was made using Muller-Hinton
      agar. Four cavities were made in agar and filled with freshly mixed materials
      after 24 h. The microorganisms were seeded by pour plate. The plates were pre
      incubated for 2 h at room temperature followed by incubation at 37C for 24 h. The
      inhibition zones diameters were measured by an independent observer. RESULTS: The
      highest mean diameters of growth inhibition zones were founded around CH and CEM
      cement. According to One-way ANOVA there was a significant difference among test
      groups (p<0.001); Post Hoc test revealed no significant difference between the
      mean zones diameter of CH and CEM cement. However, there was significant
      difference among CH and CEM cement in comparison with MTA group (p<0.001).
      CONCLUSION: It appears that CEM cement is a potent antibacterial agent like CH.

PMID- 24298291
TI  - Root canal therapy of a mandibular first molar with five root canals: a case
      report.
AB  - A mandibular first molar requiring root canal therapy was found with five canals,
      three mesial canals, and two distal canals. Initially, four canals (mesiobuccal,
      mesiolingual, distobuccal, and distolingual) were identified. The mesiobuccal and
      mesiolingual canals were found in their normal locations, and a fifth canal was
      noted between these two. This case demonstrates a rare anatomical configuration
      and supplements previous reports of the existence of such configurations in
      mandibular first molars. 

PMID- 24298292
TI  - Recent advances on the use of biochemical extracts as filaricidal agents.
AB  - Lymphatic filariasis is a parasitic infection that causes a devastating public
      health and socioeconomic burden with an estimated infection of over 120 million
      individuals worldwide. The infection is caused by three closely related nematode
      parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are
      transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera.
      The species have many ecological variants and are diversified in terms of their
      genetic fingerprint. The rapid spread of the disease and the genetic
      diversification cause the lymphatic filarial parasites to respond differently to
      diagnostic and therapeutic interventions. This in turn prompts the current
      challenge encountered in its management. Furthermore, most of the chemical
      medications used are characterized by adverse side effects. These complications
      urgently warrant intense prospecting on bio-chemicals that have potent efficacy
      against either the filarial worms or thier vector. In lieu of this, we presented
      a review on recent literature that reported the efficacy of filaricidal
      biochemicals and those employed as vector control agents. In addition, methods
      used for biochemical extraction, screening procedures, and structure of the
      bioactive compounds were also presented. 

PMID- 24298294
TI  - The next frontiers.
AB  - This issue of the IJTMB includes articles that represent the scope of therapeutic
      massage and bodywork (TMB) practice and education. The two research articles
      represent the testing of deductive hypotheses not commonly seen in the TMB
      literature: the change in tactile abnormalities of young children with autism
      using qigong massage, and changes in postural balance from massage to the muscles
      associated with the mandibular trigeminal nerve. The education editorial opens
      the IJTMB dialogue on the need, value, and issues of competency-based education
      relative to hours-based programming. 

PMID- 24298293
TI  - Child and Adolescent Obesity and Employment Sector in Urban China.
AB  - Despite its importance as a part of the economic reform in China, sectoral
      employment has been overlooked as a potential determinant of child and adolescent
      obesity (CAO). Using large-scale longitudinal data from surveys conducted from
      1989 to 2006, this paper examines the relationship between the sector in which a
      parent is employed and CAO, with the sector being based on ownership and
      categorised as either state or non-state. Analyses of over 1,700 children and
      adolescents show that children and adolescents whose parents work in the state
      sector are less likely to be obese. Patterns of sectoral employment's effect are
      robust across time periods, in fixed-effects models, and across multiple measures
      of obesity. Additionally, the paper shows that socioeconomic characteristics of
      the parent, such as income, education, and occupation, typically thought to be
      important predictors of CAO, are not as important when the parental working
      sector is included in the models.

PMID- 24298295
TI  - It's Only a Matter of Time: Clock Hours vs. Competency.
AB  - What does it mean to be competent and why is this so important? While there is no
      generally accepted definition of competency, there are key components that should
      guide the emerging movement of competency-based education (CBE). In addition,
      entry-level massage curricula typically run from approximately 500 clock hours to
      3000 hours or more. This discrepancy demonstrates markedly divergent opinions on
      what constitutes the required amount of time (content) for entry-level massage
      and bodywork curriculum. Some programs have begun using competency models, but
      there is no broad implementation of CBE. A first step is to come to some
      agreement on what competencies are actually needed for an entry-level massage
      therapist. A current effort is underway in the United States that should lay
      essential groundwork for greater adoption of CBE models. 

PMID- 24298296
TI  - Effect of facial massage on static balance in individuals with temporomandibular
      disorder - a pilot study.
AB  - INTRODUCTION: The influence of the neuromuscular system on the cervical region
      and mastication is directly associated with mandibular movements and neck
      posture. Normal occlusal homeostasis depends on complex sensory feedback
      mechanisms of the periodontal ligament, temporomandibular joint and other
      structures of the stomatognathic system. This feedback serves as a regulatory
      mechanism that helps determine the force and nature of muscle contractions.
      Alterations in the muscles of mastication, neck muscles, and occlusal
      characteristics constitute causal factors of imbalances in the postural muscle
      chains, leading to alterations in the center of pressure (CoP) of the feet. Thus,
      therapies that seek occlusal reestablishment, such as muscle relaxation
      techniques, may lead to a restructuring of the global equilibrium of the
      neuromuscular system and an improvement in body posture. PURPOSE: The aim of the
      present pilot study was to investigate the immediate effect of facial massage on
      the CoP in the anteroposterior (CoPAP) and mediolateral (CoPML) directions in
      individuals with temporomandibular disorder (TMD). METHODS: Twenty individuals
      with a diagnosis of TMD based on the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) were submitted to a facial massage
      technique. CoPAP and CoPML were evaluated using a force plate. Evaluations were
      performed under two visual conditions (eyes open and eyes closed) prior to
      resting in dorsal decubitus (baseline), after 10 minutes of rest (premassage) and
      after the administration of the massage technique (postmassage). RESULTS: No
      significant differences were found regarding CoPAP velocity with eyes open or the
      following aspects under either visual condition (eyes open or closed): CoPML
      velocity, RMS of CoPAP, RMS of CoPML, and sway area. The only significant
      difference was found for mean CoPAP velocity with eyes closed. CONCLUSIONS: While
      the results of the present study demonstrate the reliability of the reproduction
      of the data, facial massage had no immediate influence on postural control in
      individuals with TMD.

PMID- 24298297
TI  - Treatment of tactile impairment in young children with autism: results with
      qigong massage.
AB  - BACKGROUND: Following the inclusion of sensory abnormalities in the diagnostic
      criteria for autism, evidence has emerged showing that tactile abnormalities in
      young children with autism are severe, universally present, and directly related
      to delay of early self-regulation milestones required for social development.
      Parent touch is the most effective means of stimulating early self-regulation,
      yet parents of children with autism avoid touch because their children respond
      abnormally to it. This suggests that tactile abnormalities pose a barrier to
      parent touch in autism, and that treatment of tactile abnormalities may improve
      developmental outcomes. We have developed a qigong massage treatment for tactile
      abnormalities in young children with autism. Here we evaluate whether tactile
      abnormalities decrease following treatment, and whether treatment results in
      improved self-regulatory outcomes. METHODS: We retrospectively analyzed our
      qigong massage database for treatment effect on tactile abnormalities, self
      regulatory delay, and parenting stress. Five-month interval data were available
      for 129 children with autism aged 3-6 years. Of these 129, 97 received treatment
      and 32 were in the wait-list control condition. There were no differences between
      treatment and control groups by age, gender, or severity of tactile impairment.
      RESULTS: Treatment resulted in significant decreases of tactile impairment, self
      regulatory delay, and parenting stress (p < .001 on all paired t-tests); mean
      decreases were 25.5%, 24.5%, and 35.8%, respectively. Results were significant
      compared to controls [F(3,122) = 11.27, p < .001]. In the pretreatment data,
      tactile impairment was directly related to self-regulatory delay; post-treatment,
      both variables decreased proportionally. CONCLUSION: Results demonstrate that
      tactile impairment in young children with autism is treatable with a qigong
      massage protocol. The direct relationship between tactile impairment and self
      regulatory delay pretreatment, and the proportional decrease of both following
      treatment, suggest that tactile impairment is a cause of self-regulatory delay,
      and that qigong massage is a promising avenue to improve developmental outcomes
      in autism.

PMID- 24298300
TI  - [Abnormal EEG in pediatric neurology: 500 records at the Maternity and Pediatric
      Hospital, Yaounde (Cameroon)].

PMID- 24298299
TI  - Mechanisms of Gadographene-Mediated Proton Spin Relaxation.
AB  - Gd(III) associated with carbon nanomaterials relaxes water proton spins at an
      effectiveness that approaches or exceeds the theoretical limit for a single bound
      water molecule. These Gd(III)-labeled materials represent a potential
      breakthrough in sensitivity for Gd(III)-based contrast agents used for magnetic
      resonance imaging (MRI). However, their mechanism of action remains unclear. A
      gadographene library encompassing GdCl3, two different Gd(III)-complexes,
      graphene oxide (GO), and graphene suspended by two different surfactants and
      subjected to varying degrees of sonication was prepared and characterized for
      their relaxometric properties. Gadographene was found to perform comparably to
      other Gd(III)-carbon nanomaterials; its longitudinal (r1) and transverse (r2)
      relaxivity is modulated between 12-85 mM-1s-1 and 24-115 mM-1s-1, respectively,
      depending on the Gd(III)-carbon backbone combination. The unusually large
      relaxivity and its variance can be understood under the modified Florence model
      incorporating the Lipari-Szabo approach. Changes in hydration number (q), water
      residence time (tauM), molecular tumbling rate (tauR), and local motion (taufast)
      sufficiently explain most of the measured relaxivities. Furthermore, results
      implicated the coupling between graphene and Gd(III) as a minor contributor to
      proton spin relaxation.

PMID- 24298298
TI  - Developmental expression of the Nfe2-related factor (Nrf) transcription factor
      family in the zebrafish, Danio rerio.
AB  - Transcription factors in the CNC-bZIP family (NFE2, NRF1, NRF2 and NRF3) regulate
      genes with a wide range of functions in response to both physiological and
      exogenous signals, including those indicating changes in cellular redox status.
      Given their role in helping to maintain cellular homeostasis, it is imperative to
      understand the expression, regulation, and function of CNC-bZIP genes during
      embryonic development. We explored the expression and function of six nrf genes
      (nfe2, nrf1a, nrf1b, nrf2a, nrf2b, and nrf3) using zebrafish embryos as a model
      system. Analysis by microarray and quantitative RT-PCR showed that genes in the
      nrf family were expressed throughout development from oocytes to larvae. The
      spatial expression of nrf3 suggested a role in regulating the development of the
      brain, brachia and pectoral fins. Knock-down by morpholino anti-sense
      oligonucleotides suggested that none of the genes were necessary for embryonic
      viability, but nfe2 was required for proper cellular organization in the
      pneumatic duct and subsequent swim bladder function, as well as for proper
      formation of the otic vesicles. nrf genes were induced by the oxidant tert
      butylhydroperoxide, and some of this response was regulated through family
      members Nrf2a and Nrf2b. Our results provide a foundation for understanding the
      role of nrf genes in normal development and in regulating the response to
      oxidative stress in vertebrate embryos. 

PMID- 24298301
TI  - Coronary artery to pulmonary artery fistula.
AB  - PATIENT: Male, 69 FINAL DIAGNOSIS: Coronary artery to pulmonary artery fistula
      Symptoms: Chest pain Medication: - Clinical Procedure: Echocardiography *
      angiography * surgical intervention Specialty: Cardiology * Cardiac Surgery.
      OBJECTIVE: Rare disease. BACKGROUND: A coronary artery fistula is an abnormal
      communication between a coronary artery and one of the cardiac chambers or a
      great vessel, so bypassing the myocardial capillary network. They are usually
      discovered incidentally upon coronary angiography. Clinical manifestations are
      variable depending on the type of fistula, the severity of shunt, site of shunt,
      and presence of other cardiac condition. CASE REPORT: We report a 69-year-old man
      without any previous medical history, who was admitted to our hospital with chest
      pain. The electrocardiogram (ECG) showed a sinus rhythm with ST depression in V2
      to V6 precordial leads. Coronary angiography revealed a coronary artery fistula
      from left anterior descending coronary artery (LAD) to the main pulmonary artery,
      right coronary artery blockage and significant stenoses on the LAD and left
      circumflex artery (LCX). CONCLUSIONS: Surgical treatment was chosen because of
      the total occlusion of the right coronary artery and to relieve of pain to
      improve quality of life.

PMID- 24298302
TI  - Retroperitoneal hemorrhage associated with bone marrow trephine biopsy.
AB  - PATIENT: Male, 19 FINAL DIAGNOSIS: Hyperleukocytosis * thrombocytosis SYMPTOMS:
      Hyperleukocytosis * retroperitoneal hemorrhage * thrombocytosis MEDICATION: -
      Clinical Procedure: Bone marrow trephine biopsy Specialty: Hematology *
      Radiology. OBJECTIVE: Diagnostic/therapeutic accidents. BACKGROUND: Bone marrow
      (BM) trephine biopsy is generally a safe procedure, but adverse events such as
      retroperitoneal hemorrhage (RPH) may occur. We report 3 cases of this
      complication. CASE REPORT: A 19-year-old male with thrombocytopenia and
      coagulopathy underwent BM trephine biopsy to confirm relapse of acute
      lymphoblastic leukemia. Two hours later, he developed severe hypotension and a CT
      scan revealed a massive RPH, and was treated conservatively. The RPH recurred 2
      weeks after chemotherapy and was successfully treated with gel foam embolization.
      A 55-year-old male with coagulopathy underwent BM trephine biopsy for
      hyperleukocytosis and thrombocytosis. He developed a large RPH preceded by left
      lumbar dermatome sensory neuropathy. He was treated conservatively. A 56-year-old
      overweight woman on aspirin underwent BM trephine biopsy for polycythemia. Twelve
      hours later she developed severe abdominal pain with hypotension. A CT scan
      showed a massive RPH and secondary hemothorax. She was treated conservatively and
      the RPH resolved after several months. CONCLUSIONS: We and others showed that
      myeloproliferative neoplasm, quantitative or qualitative platelet abnormalities,
      aspirin, coagulopathy, and obesity are associated with development of RPH
      following BM trephine biopsy. Early diagnosis and intervention are crucial.
      Correction of coagulopathy and cessation of anti-platelet treatment prior to
      biopsy can prevent this serious complication.

PMID- 24298303
TI  - Postoperative left ventricular apical ballooning: Transient Takotsubo
      cardiomyopathy following orthotopic liver transplantation.
AB  - PATIENT: Female, 51 FINAL DIAGNOSIS: Takotsubo cardiomyopathy Symptoms: -
      MEDICATION: - Clinical Procedure: - Specialty: Cardiology * Transplantology.
      OBJECTIVE: Rare disease. BACKGROUND: Left ventricular apical ballooning syndrome
      (LVAB), also known as Takotsubo cardiomyopathy, is a cardiac syndrome
      characterized by transient left ventricular dysfunction in the absence of
      obstructive atherosclerotic coronary artery disease. An episode of emotional
      stress, typically in female patients, is believed to precede and trigger the
      development of this syndrome. CASE REPORT: We report a case of Takotsubo
      cardiomyopathy that developed after orthotopic liver transplantation in a 51-year
      old woman. On D2 (day 2) the patient had severe hemodynamic compromise.
      Echocardiography showed systolic dysfunction of the left ventricle (LV), with
      ejection fraction (EF) of 20% and anteroapical akinesis and ballooning of the
      apical 2/3 of the LV. Troponin T was elevated but other markers of myocardial
      necrosis were negative, as was coronary angiography. From D7 onward, there was an
      improvement in the hemodynamics in conjunction with a gradual increase of LV EF.
      The patient was dismissed from the hospital on D30 with signs of normal cardiac
      function and LV motion and EF of 50%. Liver function was also excellent.
      CONCLUSIONS: Every major operation, including liver transplantation, is
      associated with emotional stress for the patient. Therefore, it is necessary to
      consider Takotsubo cardiomyopathy in the differential diagnosis of heart failure
      developing early after LT, and clinicians should subsequently use adequate
      diagnostic and therapeutic measures.

PMID- 24298304
TI  - A rare case intractable diarrhea secondary to Clostridium difficile and
      cytomegalovirus coinfection.
AB  - PATIENT: Male, 63 FINAL DIAGNOSIS: Cytomegalo virus (CMV) infection Symptoms:
      Diarrhea Medication:- Clinical Procedure:- Specialty: Infectious Diseases.
      OBJECTIVE: Unusual clinical course. BACKGROUND: Coinfection with cytomegalovirus
      in a patient with Clostridium difficile persistent diarrhea and colitis can lead
      to a delay in diagnosis and treatment. CASE REPORT: A 63-year-old man with
      squamous cell carcinoma of the lower lip, status post surgical resection and
      currently on chemoradiation presented with intractable diarrhea and abdominal
      pain. Initial workup showed Clostridium difficile diarrhea with pancolitis.
      Diarrhea persisted despite being on antibiotics and bacteriological cure for C.
      difficile. Further noninvasive work up revealed associated cytomegalovirus
      infection, and patient had a dramatic response to ganciclovir without any
      relapse. CONCLUSIONS: Physicians should be cognizant about other causes of
      diarrhea and colitis in immunocompromised patient when treatment for primary
      diagnosis fails to resolve their symptoms.

PMID- 24298305
TI  - Salmonella typhimurium abscess of the chest wall.
AB  - PATIENT: Male, 73 FINAL DIAGNOSIS: Salmonella typhimurium abscess of the chest
      wall Symptoms: - MEDICATION: Ciprofloxacin Clinical Procedure:- Specialty:
      Infectious Diseases. OBJECTIVE: Unusual clinical course. BACKGROUND: Non-typhoid
      Salmonella extra-intestinal infections usually develop in infants and in adult
      patients with pre-existing predisposing conditions. Blood stream infections and
      urinary tract infections are the most common clinical presentations, but other
      sites of infection may be involved as well. CASE REPORT: We describe a case of
      invasive salmonellosis caused by Salmonella typhimurium involving the chest wall
      in a 73-year-old man. The patient had suffered from gastroenteritis followed by
      left basal pneumonia with pleural effusion 7 weeks before. The CT scan of the
      chest wall showed a pericostal abscess with shirt-stud morphology near the left
      last cartilaginous arch. The abscess was surgically drained and patient was cured
      after a 40-day ciprofloxacin treatment. CONCLUSIONS: A review of the literature
      on extra-intestinal non-typhoid salmonellosis shows that pleuropulmonary and soft
      tissue infections are uncommon. We argue that non-typhoid Salmonella might be
      considered as a possible cause of chest wall abscess in individuals with recent
      history of gastroenteritis complicated by pneumonia and pleural effusion.

PMID- 24298306
TI  - Guest editors Paolo Decuzzi & John P. Cooke lend expertise on special
      regenerative medicine issue.

PMID- 24298307
TI  - Regenerative medicine in cardiovascular disease: introduction.

PMID- 24298308
TI  - Stem cell therapy for heart failure.
AB  - The last decade has witnessed the publication of a large number of clinical
      trials primarily using bone marrow-derived stem cells as the injected cell. These
      "first-generation" clinical trials have advanced our understanding and shown us
      that (1) cell therapy is safe, (2) cell therapy has been modestly effective, and
      (3) in humans, bone marrow-derived stem cells do not transdifferentiate into
      cardiomyocytes or new blood vessels (or at least in sufficient numbers to have
      any effect). The primary mechanism of action for cell therapy is now believed to
      be through paracrine effects that include the release of cytokines, chemokines,
      and growth factors that inhibit apoptosis and fibrosis, enhance contractility,
      and activate endogenous regenerative mechanisms through endogenous circulating or
      site-specific stem cells. The new direction for clinical trials includes the use
      of stem cells capable of cardiac lineage, such as endogenous cardiac stem cells. 

PMID- 24298309
TI  - Use of stem cells in heart failure treatment: where we stand and where we are
      going.
AB  - End-stage heart failure is the final common pathway of an irreversible process
      associated with loss of myocardial cells. In this process, the capacity for
      renewal and repair of myocardial tissue is inadequate and ultimately leads to
      ventricular remodeling. Novel therapeutic strategies have been developed to
      prevent it, one being cell therapy, which has emerged as a potential approach to
      directly repopulate and repair the damaged heart. Here, we review the use of
      regenerative cell therapy for different cardiac diseases and discuss the positive
      effect of cell therapy mediated by paracrine factors instead of turning directly
      into cardiomyocytes. 

PMID- 24298310
TI  - Clinical trials of adult stem cell therapy for peripheral artery disease.
AB  - Peripheral artery disease (PAD) refers to noncoronary vascular disease affecting
      the peripheral arteries. Most commonly the term is applied to occlusive arterial
      disease affecting the limb arteries, typically due to atherosclerosis.
      Preclinical studies indicate that a variety of stem cell therapies provide growth
      factors and cytokines for therapeutic angiogenesis. Small clinical trials with
      bone marrow mononuclear cells, as well as other cell types, have shown promise.
      However, mechanisms of therapeutic effect, if any, are not understood. Definitive
      clinical trials are needed to determine if there are any beneficial effects on
      functional capacity or morbidity. 

PMID- 24298311
TI  - Induced pluripotent stem cells: how they will change the practice of
      cardiovascular medicine.
AB  - Induced pluripotent stem cells (iPSCs) can be generated from adult somatic
      tissues by the forced expression of a few defined transcription factors,
      including Oct4, Sox2, Klf4, and c-Myc. iPSC technology holds tremendous promises
      for therapeutic cardiovascular regeneration because of the cells' unlimited
      capacity for proliferation and differentiation into all cell lineages. The iPSCs
      can be generated from somatic cells of patients with a genetic basis for their
      disease so as to understand the pathobiology of the disorder. This disease
      modeling can be adapted to high-throughput screens to discover new therapeutic
      molecules. Finally, the iPSC technology may enable personalized cell therapies,
      while avoiding the ethical concerns surrounding human embryonic stem cells.
      Intensive efforts are underway to develop reliable methods to guide stem cell
      differentiation into cardiovascular lineages in the treatment of peripheral
      artery disease and heart diseases. Studies of disease pathogenesis and drug
      discovery using iPSC technology shall advance the discovery of novel treatments
      for cardiovascular diseases. 

PMID- 24298312
TI  - Therapeutic transdifferentiation: can we generate cardiac tissue rather than scar
      after myocardial injury?
AB  - After myocardial injury, the cardiac muscle does not regenerate and heals by
      forming a scar. This process results in loss of heart function and ultimately
      heart failure. Recent application of reprogramming technology, where forced
      expression of master regulators convert scar-forming cells to become
      cardiovascular cells in vivo, has fueled new hope for the development of
      therapies targeting heart disease. 

PMID- 24298313
TI  - Building a tissue in vitro from the bottom up: implications in regenerative
      medicine.
AB  - Tissue engineering aims at creating biological tissues to improve or restore the
      function of diseased or damaged tissues. To enhance the performance of engineered
      tissues, it is required to recapitulate in vitro not only the composition but
      also the structural organization of native tissues. To this end, tissue
      engineering techniques are beginning to focus on generating micron-sized tissue
      modules having specific microarchitectural features that can be used alone as
      living filler in the damaged areas or serve as building blocks to engineer large
      biological tissues by a bottom-up approach. This work discusses the shortcomings
      related to traditional "top-down" strategies and the promises of emerging
      ''bottom-up" approaches in creating engineered biological tissues. We first
      present an overview of the current tissue-building techniques and their
      applications, with an analysis of the potentiality and shortcomings of different
      approaches. We then propose and discuss a novel method for the biofabrication of
      connective-like micro tissues and how this technique can be translated to cardiac
      muscle fabrication. 

PMID- 24298314
TI  - Imaging cardiac stem cell transplantation using radionuclide labeling techniques:
      clinical applications and future directions.
AB  - Stem cell therapy is emerging as a potential new therapy for patients with
      advanced heart failure. In recent years, advances in molecular imaging have
      allowed monitoring of stem cell homing and survival. In this review article, we
      will discuss the clinical application and future directions of stem cell imaging
      in advanced heart failure. 

PMID- 24298316
TI  - Update on the Houston Methodist DeBakey Heart & Vascular Center cardiac stem cell
      studies.

PMID- 24298315
TI  - Patient-specific computational modeling and magnetic nanoconstructs: tools for
      maximizing the efficacy of stem cell-based therapies.
AB  - Stem cell transplantation has the potential to restore heart function following
      myocardial infarction. However, the success of any stem cell-based therapy is
      critically linked to the effective homing and early engraftment of the injected
      cells at the infarcted site. Here, a hierarchical multiscale computational model
      is proposed for predicting the patient-specific vascular transport and
      intratissue homing and migration of stem cells injected either systemically or
      locally. Starting with patient-specific data, such as the vascular geometry,
      blood flow, and location of the infarcted area, the computational model can be
      used to perform parametric analysis to identify optimal injection conditions in
      terms of administration route, injection site, catheter type, and infusion
      velocity. In addition to this, a new generation of magnetic nanoconstructs is
      introduced for labeling stem cells and monitoring their behavior in vivo via
      magnetic resonance imaging. These nanoconstructs also can be used for multimodal
      imaging, merging MRI and nuclear imaging, and the intracellular delivery of
      active agents to support stem cell differentiation. The convergence of
      computational modeling and novel nanoconstructs for stem cell labeling could
      improve our understanding in cell homing and early engraftment at the infarcted
      site and thus pave the way to more effective stem cell-based therapies. 

PMID- 24298317
TI  - IgG4 related cardiac disease.
AB  - IgG4-related systemic disease is an inflammatory disorder that can affect many
      organs. This case report describes a patient who in 2004 was found to have an
      inflammatory pseudotumor with IgG4 pathology. Over the next 3 years, visual
      symptoms responded well to recurrent courses of prednisone. In 2009, the patient
      developed chest pain and bradycardia with subsequent third-degree heart block,
      necessitating placement of a pacemaker. A subsequent PET scan showed extensive
      involvement of multiple organs as described in IgG4 disease as well as
      involvement of the myocardium and SA node. Pseudotumors involving the heart have
      been reported but have not been shown to be related to IgG4 disease. Although
      there was no pathology confirmation of heart involvement, the nature and extent
      of the organ involvement led us to conclude that it was due to IgG4-related
      disease. The use of the PET scan may help identify involvement of the myocardium.

PMID- 24298318
TI  - Pulsating suprasternal lump: a diagnostic and management dilemma.
AB  - We report a 70-year-old female who complained of shortness of breath and a
      pulsating suprasternal lump. CT scan showed innominate artery dilatation. In
      addition, operative exposure showed tortuous arteries and a common origin of the
      left common carotid and innominate arteries. Surgical correction by innominate
      artery division and reimplantation at the ascending aorta was performed, and the
      patient's symptoms completely disappeared after the procedure. 

PMID- 24298319
TI  - The judicious use of antimicrobial therapy: just because you can doesn't mean you
      should.

PMID- 24298320
TI  - Museum of TMH multimodality imaging center: cardiac amyloidosis.

PMID- 24298323
TI  - The fisherman.

PMID- 24298325
TI  - Differences in trauma history and psychopathology between PTSD patients with and
      without co-occurring dissociative disorders.
AB  - BACKGROUND: The interplay between different types of potentially traumatizing
      events, posttraumatic symptoms, and the pathogenesis of PTSD or major
      dissociative disorders (DD) has been extensively studied during the last decade.
      However, the phenomenology and nosological classification of posttraumatic
      disorders is currently under debate. The current study was conducted to
      investigate differences between PTSD patients with and without co-occurring major
      DD with regard to general psychopathology, trauma history, and trauma-specific
      symptoms. METHODS: Twenty-four inpatients were administered the Clinician
      Administered PTSD Scale for DSM-IV (CAPS) and the Mini-Structured Clinical
      Interview for DSM-IV Dissociative Disorders (MINI-SKID-D) to assess DD and PTSD.
      Additionally, participants completed questionnaires to assess general
      psychopathology and health status. RESULTS: Symptom profiles and axis I
      comorbidity were similar in all patients. Traumatic experiences did not differ
      between the two groups, with both reporting high levels of childhood trauma. Only
      trauma-specific avoidance behavior and dissociative symptoms differed between
      groups. CONCLUSION: Results support the view that PTSD and DD are affiliated
      disorders that could be classified within the same diagnostic category. Our
      results accord with a typological model of dissociation in which profound forms
      of dissociation are specific to DD and are accompanied with higher levels of
      trauma-specific avoidance in DD patients.

PMID- 24298326
TI  - Risk practices for animal and human anthrax in Bangladesh: an exploratory study.
AB  - INTRODUCTION: From August 2009 to October 2010, International Centre for
      Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease
      Control and Research together investigated 14 outbreaks of anthrax which included
      140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation
      objectives were to explore the context in which these outbreaks occurred,
      including livestock rearing practices, human handling of sick and dead animals,
      and the anthrax vaccination program. METHODS: Field anthropologists used
      qualitative data-collection tools, including 15 hours of unstructured
      observations, 11 key informant interviews, 32 open-ended interviews, and 6 group
      discussions in 5 anthrax-affected villages. RESULTS: Each cattle owner in the
      affected communities raised a median of six ruminants on their household
      premises. The ruminants were often grazed in pastures and fed supplementary rice
      straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake;
      lactating cows were given dicalcium phosphate. Cattle represented a major
      financial investment. Since Islamic law forbids eating animals that die from
      natural causes, when anthrax-infected cattle were moribund, farmers often
      slaughtered them on the household premises while they were still alive so that
      the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners
      removed and sold the hides from discarded carcasses. Farmers discarded the
      carcasses and slaughtering waste into ditches, bodies of water, or open fields.
      Cattle in the affected communities did not receive routine anthrax vaccine due to
      low production, poor distribution, and limited staffing for vaccination.
      CONCLUSION: Slaughtering anthrax-infected animals and disposing of butchering
      waste and carcasses in environments where ruminants live and graze, combined with
      limited vaccination, provided a context that permitted repeated anthrax outbreaks
      in animals and humans. Because of strong financial incentives, slaughtering
      moribund animals and discarding carcasses and waste products will likely
      continue. Long-term vaccination coverage for at-risk animal populations may
      reduce anthrax infection.

PMID- 24298327
TI  - Spatial analysis of positive and negative Q fever laboratory results for
      identifying high- and low-risk areas of infection in the Netherlands.
AB  - BACKGROUND: The Netherlands faced a large Q fever epidemic from 2007 to 2010, in
      which thousands of people were tested for the presence of antibodies against
      Coxiella burnetii as part of individual patient diagnosis. So far, only data of
      notified cases were used for the identification of high-risk areas, which can
      lead to misclassification of risk. Therefore, we identified high- and low-risk
      areas based on laboratory test results to make control measures more efficient.
      METHODS: Data on diagnostic Q fever laboratory tests were obtained from two
      regional laboratories of medical microbiology in the high-incidence area in the
      south of the Netherlands. The proportion of patients testing positive was mapped
      per postal code area. Patients testing positive were compared to patients testing
      negative based on the distance between residential address and the nearest
      infected goat farm with adjustment for age and sex. RESULTS AND CONCLUSION: Of
      11,035 patients tested, 4,011 (36.4%) had a positive laboratory test result for Q
      fever. Maps showing the spatial pattern of tests performed and proportion of
      positive tests allowed for the identification of high- and low-risk Q fever
      areas. The proportion of patients testing positive was higher in areas close to
      infected goat farms compared to areas further away. Patients living <1 km from an
      infected goat farm had a substantially higher risk of testing positive for
      antibodies to C. burnetii than those living >10 km away (OR 21.70, 95% CI 16.28
      28.92). Laboratory test results have the potential to make control measures more
      efficient by identifying high-risk areas as well as low-risk areas.

PMID- 24298328
TI  - Reprogrammed pluripotent stem cells from somatic cells.
AB  - Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into
      all cell types. So, these cells can be a biological resource for regenerative
      medicine. However, ES cells known as standard pluripotent cells have problem to
      be used for cell therapy because of ethical issue of the origin and immune
      response on the graft. Hence, recently reprogrammed pluripotent cells have been
      suggested as an alternative source for regenerative medicine. Somatic cells can
      acquire the ES cell-like pluripotency by transferring somatic cell nuclei into
      oocytes, by cell fusion with pluripotent cells. Retroviral-mediated introduction
      of four factors, Oct4, Sox2, Klf4 and c-Myc can successfully reprogram somatic
      cells into ES cell-like pluripotent stem cells, known as induced pluripotent stem
      (iPS) cells. These cells closely resemble ES cells in gene expression pattern,
      cell biologic and phenotypic characteristics. However, to reach the eventual goal
      of clinical application, it is necessary to overcome the major drawbacks such as
      low reprogramming efficiency and genomic alterations due to viral integration. In
      this review, we discuss the current reprogramming techniques and mechanisms of
      nuclear reprogramming induced by transcription factor transduction. 

PMID- 24298329
TI  - Human embryonic stem cells: derivation, maintenance and cryopreservation.
AB  - Human embryonic stem cells (hESCs) are the most powerful candidate for the
      treatment of incurable diseases through the replacement of damaged cells and/or
      tissues in patients, although there are some obstacles to overcome for the
      clinical application of hESCs such as the assurance of guided differentiation and
      control of the immune response following cell therapy or tissue grafting. To
      obtain genetically stable hESCs and use them clinically, it is important to
      develop appropriate culture conditions. Additionally, the establishment of a hESC
      bank with a large number of hESC lines will be required for their clinical
      application because each hESC line is directed to have a different
      differentiation ability and immune characteristics such as HLA type. In this
      review, we describe the derivation and culture conditions of hESCs based on
      recent advances. Then, we will introduce several cryopreservation methods for
      hESCs, which is important for the development of cell bank. 

PMID- 24298330
TI  - Tgf-Beta family signaling in embryonic stem cells.
AB  - Ligands of transforming growth factor beta (TGF-beta) family members have been
      implicated in the development and patho-physiological process of various organs.
      Embryonic stem cells (ESCs) are characterized by their ability to proliferate
      indefinitely and differentiated into all three germ layer cells, which are termed
      as pluripotency and self-renewal,respectively. For successful therapeutic
      application of ESCs, it is essential to understand the mechanisms underlying self
      renewal and pluripotency, which involve complex networks among key factors
      including transcription factors, epigenetic control, microRNAs and signaling
      pathways. In this review, we discuss recent progress on the function of TGF beta
      family ligands and their canonical SMAD signaling in the maintenance of ESC' s
      identity. 

PMID- 24298331
TI  - Differentiation of hESCs into Mesodermal Subtypes: Vascular-, Hematopoietic- and
      Mesenchymal-lineage Cells.
AB  - To date, studies on the application of mesodermally derived mesenchymal-,
      hematopoietic- and vascular-lineage cells for cell therapy have provided either
      poor or insufficient data. The results are equivocal with regard to therapeutic
      efficiency and yield. Since the establishment of human embryonic stem cells
      (hESCs) in 1998, the capacity of hESCs to differentiate into various mesodermal
      lineages has sparked considerable interest in the regenerative medicine
      community, a group interested in generating specialized cells to treat patients
      suffering from degenerative diseases. Even though hESCs are sensitive, effective
      methods for guiding the differentiation of hESCs into specific mesodermal cell
      types are still being developed. In addition, to understand the functional
      properties of hESC derivatives, numerous animal model studies have been performed
      by many research groups over the last decade. In this review, we describe and
      summarize the protocols currently used for differentiation of hESCs into multiple
      mesodermal lineages and their therapeutic efficiency in different animal models.
      Furthermore, we discuss the technical hurdles associated with each protocol and
      the safety of hESC derivatives for therapeutic applications. Technical
      improvement of the methods used to produce hESC derivatives for therapeutic use
      in patients with degenerative diseases should remain an objective of future
      studies, as should the development of effective and stable induction systems. 

PMID- 24298332
TI  - Differentiation into Endoderm Lineage: Pancreatic differentiation from Embryonic
      Stem Cells.
AB  - The endoderm gives rise to digestive and respiratory tracts, thyroid, liver, and
      pancreas. Representative disease of endoderm lineages is type 1 diabetes
      resulting from destruction of the insulin-producing beta cells. Generation of
      functional beta cells from human embryonic stem (ES) cells in vitro can be
      practical, renewable cell source for replacement cell therapy for type 1
      diabetes. It has been achieved by progressive instructive differentiation through
      each of the developmental stages. In this article, important studies of
      differentiation into pancreatic beta cells from ES cells are reviewed through
      pancreatic developmental stages as definitive endoderm, primitive gut
      tube/foregut, and pancreatic cells. The investigation of differentiating ES cells
      from definitive endoderm to pancreas using signaling, arrays, and proteomics is
      also introduced. 

PMID- 24298333
TI  - Potential role of bone marrow mesenchymal stem cells in obstructive sleep apnea.
AB  - Obstructive sleep apnea syndrome (OSA) is a prevalent disease caused by increased
      collapsibility of the upper airway. OSA induces oxidative stress, inflammation
      and endothelial dysfunction, with important clinical consequences such as
      neurocognitive alterations and cardiovascular diseases. Although it has been
      shown that bone marrow-derived stem cells play a protective and reparative
      function in several diseases involving inflammatory processes and endothelial
      dysfunction, the data currently available on the potential role of adult stem
      cells in OSA are scarce. The present review presents recent data on the potential
      role of bone marrow-derived mesenchymal stem cells (MSC) in OSA. The results
      obtained in animal models that realistically mimic the events characterizing this
      sleep breathing disorder strongly support the notion that MSC are mobilized in
      circulating blood and then activated to play an anti-inflammatory role in OSA. 

PMID- 24298334
TI  - Preconditioning of Human Skeletal Myoblast with Stromal Cell-derived Factor
      1alpha Promotes Cytoprotective Effects against Oxidative and Anoxic Stress.
AB  - BACKGROUND AND OBJECTIVES: The incidence of human autologous transplanted
      skeletal myoblast (SkM) cell death in ischemic myocardium was higher in the first
      few days after cell therapy. We proposed that human SkM treated by human stromal
      cell-derived factor (SDF-1alpha) protein or tranfected by SDF-1alpha,
      precondition them against oxidative or anoxic injury. METHODS AND RESULTS: The
      purification of human SkM (80~90%) culture was assessed for desmin and CXCR4
      expression using immunostaining and flow cytometry respectively. Cells were
      transfected to overexpress SDF-1alpha or treated with rSDF-1alpha (10~200 ng/ml,
      1~4 h) were either exposed to anoxia or treated with 100MUM H2O2 for different
      time periods (1~6 h anoxia) (1~3 h H2O2). Optimized conditions for transfection
      of SDF-1alpha gene into human SkM were achieved, using FuGene(TM)6/phSDF
      1alpha(3:2 v/w, 4 h transfection) with 125MU M ZnCl2 (p< 0.001), up to 7 days
      post-transfection as compared with transfected SkM without ZnCl2 and non
      transfected control cells. Transfection efficiency was assessed by
      immunostaining, ELISA, western blots and PCR. LDH analysis showed significant
      decrease in release of LDH after exposure to 6 h anoxia or 100MU M H2O2 for 2 h
      as compared with the normal un-treated or un-transfected SkM (p< 0.001). In
      western blots assay, SDF-1alpha over-expressing human SkM or treated with rSDF
      1alpha induced marked expression of total Akt (1.2-fold) and phospho-Akt (2.7
      fold), Bcl2 (1.6-fold) and VEGF (5.8-fold) after exposure to 6 h anoxia as
      compared with human SkM controls. CONCLUSIONS: The preconditioning of donor
      transplanted human SkM with SDF-1alpha increased cell survival and promoted
      cytoprotective effect against oxidative or anoxic injury that may be an
      innovative approach for clinical application.

PMID- 24298335
TI  - Influence of Autologus Adipose Derived Stem Cells and PRP on Regeneration of
      Dehiscence-Type Defects in Alveolar Bone: A Comparative Histochemical and
      Histomorphometric Study in Dogs.
AB  - BACKGROUND AND OBJECTIVES: Autogenous bone grafts is considered to be the best
      choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs)
      represents a promising tool for new clinical concepts in supporting cellular
      therapy. The goal of our study was to investigate bone regeneration following
      application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at
      dehiscence-type defects in alveolar bone in dogs. METHODS AND RESULTS:
      Standardized buccal dehiscence defects (4* 3*3 mm) were surgically created in
      eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or
      without grafting material. Three months later; a bone core was harvested from
      grafted and non grafted sites for histological, histochemical and
      histomorphometric assessment. There was no evidence of inflammation or adverse
      tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a
      significantly higher result (p<= 0.05), with a mean area % of spongy bone and
      compact bone of (64.96+/-5.37 and 837.62+/-24.95), compared to ASCs alone
      (47.65+/-1.43 and 661.92+/-12.65) and without grafting (33.55+/- 1.74 and
      290.85+/-7.27) respectively. The area % of lamellated bone increased
      significantly reaching its highest level in group A followed by group B. Also a
      significant increase in area % of neutral mucopolysaccharides and calcified
      reactivity of Masson|s Trichrome stain in groups A and B compared to group C was
      obtained. CONCLUSIONS: Our results suggest that, the addition of PRP to ASCs
      enhances bone formation after 3 months and may be clinically effective in
      accelerating postsurgical healing in both periodontal and maxillofacial surgical
      applications.

PMID- 24298336
TI  - Human Embryonic-like ECM (hECM) Stimulates Proliferation and Differentiation in
      Stem Cells While Killing Cancer Cells.
AB  - BACKGROUND AND OBJECTIVES: There are a number of unique processes seen in the
      developing fetus that cease post-partum including that tumors rarely form, and
      scar-less wound healing and digit regeneration occur. In addition, cancer lines
      have been "reprogrammed" by co-culture with embryonic extracellular matrix (ECM).
      METHODS AND RESULTS: We have developed a naturally secreted human ECM (hECM) with
      embryonic-like characteristics which is secreted by neonatal fibroblasts grown in
      microcarrier suspension cultures under hypoxia. This upregulates a number of
      substances associated with stem cell niches in the body including various
      laminins, Collagen 4, CXCL12, NID1, NID2, and NOTCH2. hECM has been shown to
      support proliferation of hESCs and MSCs and diminish or eliminate tumor load in
      melanoma (B16), adenocarcinoma (MDA-MB-435), colon cancer (HT29) and glioma (C6)
      in both in vitro and in vivo animal studies. In the tumor chorioallantoic
      membrane (tumcam) model hECM significantly inhibited tumor growth and in
      subcutaneous mouse xenograft experiments, tumor growth was inhibited from 70~90%.
      Co-cultures of fibroblasts and mesothelioma show support of fibroblast expansion
      with a concurrent inhibition of mesothelioma. The inhibitory affect is selective
      for cancer cells and cancer stem cells through the upregulation of Caspase 9
      which forces the cells into apoptosis. CONCLUSIONS: These data show that hECM has
      the potential to show benefit in the treatment of various cancers as a coating
      for biopsy needle, tissue filler post tumor removal, and as an injectable into
      the tumor site.

PMID- 24298337
TI  - Potential impact of mature adipocyte dedifferentiation in terms of cell numbers.
AB  - Mature adipocytes possess the capability to dedifferentiate and form
      proliferative-competent progeny cells. Little is currently known about the
      daughter cells, or the impact of such in vitro physiology in an in vivo
      situation, and the daughter cells may actually represent cells with stem-like
      cell potential. The present paper introduces implications of and impact of this
      physiology in terms of animal adiposity and composition. 

PMID- 24298338
TI  - Science and ethics: bridge to the future for regenerative medicine.
AB  - The objective of this article is to reflect on the relationship between
      regenerative medicine and ethics, using as references the Aristotelian concept of
      what is ethical and that of Raessler Van Potter about bioethics. To do this, I
      will briefly describe the advances in regenerative medicine with stem cells, the
      strategies for producing pluripotential cells without destroying human embryos,
      and the great potential of stem cells to improve life for Humanity, noting that
      for this to be possible, it is necessary to locate the role of regenerative
      medicine in the context of human values and well being. In this way, this article
      has a real perspective of the role that regenerative medicine can play in
      benefitting human beings and engendering respect for human and natural
      environments. 

PMID- 24298339
TI  - Dopamine neuron generation from human embryonic stem cells.
AB  - The capacity of pluripotency and self-renewal of human embryonic stem (hES) cells
      may provide unlimited cell source for cell replacement therapy. In this
      manuscript we summarize hES differentiation protocols coculture with PA6 or MS5
      stromal cells. After 7~ 9 days of differentiation, neural rosettes were robustly
      appeared followed by coculture with sonic hedgehog over-expressing stromal cells
      efficiently generated dopaminergic neural precursor cells. Using this protocol,
      the majority of differentiated hES cells contained nestin positive cells (>95%)
      and after final differentiation a high percentage of TuJ1 positive neurons was
      tyrosine hydroxylase positive (>40%). 

PMID- 24298340
TI  - Stem cell therapy in patients with thromboangiitis obliterans: assessment of the
      long-term clinical outcome and analysis of the prognostic factors.
AB  - BACKGROUND AND OBJECTIVES: The clinical benefits of stem cell therapy have been
      reported in patients with peripheral arterial occlusive disease. However, those
      studies had no standard reporting system to assess the outcomes, so we made a
      scoring system and assessed the outcomes of the limbs that underwent whole bone
      marrow stem cell (WBMSC) therapy. METHODS AND RESULTS: Between July 4 and June
      2009, 90 limbs of 67 patients with symptomatic thromboangiitis obliterans (TAO)
      were enrolled. Autologous whole bone marrow was implanted into the limb by
      intramuscular injections. The primary outcomes were defined by the clinical and
      angiographic improvement in all the limbs and the secondary outcomes were the
      clinical improvement and the amputation-free rates in the critical ischemic limbs
      (CILs). Clinical improvement and angiographic improvement was observed in 55.6%
      and 43.2% of all the limbs and in 50% and 50%of the CILs, respectively. The 1, 3
      and 5-year amputation-free rates were 91.9%, 88.5% and 84.6% for all the limbs,
      respectively, and 83.9%, 77.5% and 70.4% for the CILs, respectively. A history of
      sympathectomy/sympathetic block was shown to be a negative prognostic factor for
      clinical improvement in all the limbs and in the CILs. In addition, a history of
      sympathetic block/sympathectomy and the smoking state were the major predictors
      of amputation for the CILs. CONCLUSIONS: This study indicated that autologous
      WMBSC therapy improves the clinical status and reduces amputation factors in the
      limbs with symptomatic TAO and a history of sympathetic block/sympathectomy and
      the smoking state are useful prognostic factors.

PMID- 24298341
TI  - Isolation and morphological characterisation of ovine adipose-derived mesenchymal
      stem cells in culture.
AB  - BACKGROUND AND OBJECTIVES: AD-MSCs (adipose-derived mesenchymal stem cells), as
      an easy obtainable population of multipotent cells, have been successfully
      applied in many diseases in animals. Having very similar properties and
      morphology to these collected from bone marrow, are very attractive object for
      regenerative medicine. CONCLUSIONS: Ovine subcutaneous fat from many regions of
      the body is rich source of stem cells, which could be used in locomotive system
      disorders experimental therapy on sheep models.

PMID- 24298342
TI  - A study on proliferation and behavior of retinal pigment epithelial cells on
      purified alginate films.
AB  - BACKGROUND AND OBJECTIVES: Alginate, an anionic polysaccharide distributed widely
      in the cell walls of brown algae, is used in biomedical applications. However,
      alginate' s performance as a biomaterial, has limited by its several
      contamination such as endotoxins, proteins and polyphenols. METHODS AND RESULTS:
      To overcome this problem, we have developed using modified Korbutt method for
      alginate purification. After purification, we made alginate films and used for
      retinal pigment epithelial cell (RPEs) regeneration. ARPE-19 cells were seeded in
      non-purified and purified alginate films, and then cell viability and
      proliferation were estimated by MTT assay and RT-PCR was performed to assess
      specific cell expression. ARPE-19 cell-loaded alginate films were evaluated
      specific protein expression by through AEC staining and we examined the cell
      adhesion by scanning electron micro scopy (SEM). CONCLUSIONS: In this result,
      ARPE-19 cells in purified alginate films had higher cell proliferative rate and
      phenotypic expression than those on non-purified alginate films. The results
      suggest that purified alginate is useful for RPEs regeneration.

PMID- 24298343
TI  - Clinical outcome of 50 progressive multiple sclerosis patients treated with
      cellular therapy in iraq.
AB  - BACKGROUND AND OBJECTIVES: Multiple Sclerosis is a disease characterized by
      multifocal areas of demyelination in the brain and spinal cord, with associated
      inflammatory cell infiltrates, reactive gliosis, and axonal degeneration. It
      typically presents in young adults with episodic neurologic dysfunction, our aim
      is to find new simple method to treat multiple sclerosis by hematopoietic stem
      cells derived from peripheral blood. METHODS AND RESULTS: 50 patients suffering
      from multiple sclerosis worsening despite pharmacological treatment were treated
      by means of several intrathecal injections of peripheral blood cells harvested by
      aphaeresis after G-CSF(granulocyte colony stimulating factor) treatment. 24
      patients (48% ) had a reduction of EDSS score. 8 patients had a relapse, but it
      was milder than usual and more easily controlled by cortisone. CONCLUSIONS: Since
      mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a
      peripheral blood harvest seems easier and cheaper than mesenchymal cells
      cultivation prior to the injection. It seems a reasonable treatment for
      progressive multiple sclerosis.

PMID- 24298344
TI  - The Porcine Aortic Tissue Culture System in vitro for Stem Cell Research.
AB  - BACKGROUND AND OBJECTIVES: Due to the shortage of human donors for
      transplantation, the use of animal organs for xenotransplantation has come into
      great interest. Xeno-derived vessels and cardiac valves would be possible
      alternatives for the patient suffering from cardiovascular diseases. Therefore,
      we established in vitro culture system of a porcine vessel that could be helpful
      for the research of xenograft and stem cell research. METHODS AND RESULTS: We
      primarily isolated porcine thoracic aorta, cultured square-shaped pieces up to 17
      days and analyzed its morphology and characters. The endothelial cells were
      primarily isolated from cultured porcine aortic pieces and their morphology,
      function and character were analyzed in order to confirm them as endothelial
      cells at day 3, 4, 8, 10 and 17. Even at day 17, the morphology exhibited the
      intact endothelial layer as well as specifically expressed CD31 and von
      Willebrand factor. The morphology of primarily isolated cells from cultured
      tissues was identical as an endothelial cell. By flow cytometry analysis, more
      than 80% of the isolated cells expressed CD31 and up to 80% took up acetyl low
      density lipoprotein (ac-LDL) until day 10 of tissue culture period even though it
      decreased to about 50% at day 17 that means they not only showed typical
      endothelial cell characters but also functioned properly. CONCLUSIONS: We
      successfully established and optimized a porcine vascular tissue in vitro culture
      system that could be a valuable model for in vitro study of xenotransplantation
      and stem cell research.

PMID- 24298345
TI  - Human amniotic epithelial cells cultured in substitute serum medium maintain
      their stem cell characteristics for up to four passages.
AB  - BACKGROUND AND OBJECTIVES: The common applied culture medium in which human
      amniotic epithelial cells (hAECs) maintain their stem cell characteristics
      contains fetal calf serum (FCS) and thus is not compatible with possible future
      clinical applications due to the danger of animal derived pathogens. To overcome
      this problem, we replaced FCS with serum substitute supplement, a serum
      substitute used in the in vitro fertilization for embryo development, in the
      common applied culture medium and cultured hAECs in this substitute serum medium
      (SSM). METHODS AND RESULTS: Purity validation and characterization of freshly
      isolated and cultured hAECs was assessed through the expression of stem cell
      specific markers by RT-PCR (gene expression), by immunofluorescence staining and
      FACS (protein expression). Furthermore, karyotype was performed at passage four
      in order to exclude possible chromosome anomalies in hAECs cultured in SSM. The
      differentiation potential of hAECs into the cardiomyogenic lineage was tested
      through cardiac Troponin T expression by immunohistochemistry. hAECs cultured in
      SSM maintained expression of all the major pluripotent genes Sox-2, Oct-4 and
      Nanog as well as the expression of the embryonic stem cell specific surface
      antigens SSEA-4, SSEA-3 and TRA-1-60 over four passages. Using cardiac
      differentiation medium containing 10% serum substitute supplement, hAECs
      differentiated into cardiac troponin T expressing cells. CONCLUSIONS: We can
      conclude that, hAECs maintain their stem cell characteristics when cultured in
      SSM for up to 4 passages. This makes possible future clinical applications of
      these cells more feasible.

PMID- 24298346
TI  - Effect of stem cell therapy on amiodarone induced fibrosing interstitial lung
      disease in albino rat.
AB  - BACKGROUND AND OBJECTIVES: The fibrosing forms of interstitial lung disease (ILD)
      are associated with significant morbidity and mortality. ILD may be idiopathic,
      secondary to occupational, infection, complicate rheumatic diseases or drug
      induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No
      effective treatment was confirmed for pulmonary fibrosis except lung
      transplantation. The present study aimed at investigating the possible effect of
      human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was
      accomplished by using amiodarone as a model of induced lung damage in albino rat.
      METHODS AND RESULTS: Seventeen adult male albino rats were divided into 3 groups.
      Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week
      for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the
      tail vein following confirmation of lung damage and left for 4 weeks before
      sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened
      wall of pulmonary vessels were found and proved morphometrically. Reduced type I
      pneumocytes and increased area% of collagen fibers were recorded. All findings
      regressed on stem cell therapy. CONCLUSIONS: Cord blood MSC therapy proved
      definite amelioration of fibrosing interstitial lung disease provided therapy
      starts early in the development of the pathogenesis.

PMID- 24298347
TI  - Cardiac specific gene expression changes in long term culture of murine
      mesenchymal stem cells.
AB  - Murine MSCs are a readily available source of adult stem cells enabling extensive
      in vitro study of this cell population. MSCs have been described as multipotent,
      and have been proven capable of differentiation into several connective tissue
      types. Furthermore some studies have suggested an ability to differentiate into
      non-connective tissue cell types such as the cardiomyocyte. The aim of this study
      was to differentiate murine MSCs toward cardiac lineage with the commonly used
      method of culture with 5' Azacytidine. Critically, baseline analysis of gene
      expression of passage four MSCs demonstrated expression of key cardiac markers
      including cardiac troponin T and I, and the ryanodine receptor. Furthermore,
      expression analysis of these genes changed with time in culture and passage
      number. However, there was no significant alteration when cells were subjected to
      a differentiation protocol. This study therefore highlights the importance of
      analyzing baseline cells extensively, and indicates the limitations in
      extrapolating data for comparison between species. Furthermore this data brings
      into question the efficacy of cardiac differentiation using MSCs. 

PMID- 24298348
TI  - Engineering biomaterials for feeder-free maintenance of human pluripotent stem
      cells.
AB  - Human pluripotent stem cells (hPSCs) are capable of differentiating into any type
      of somatic cell, a characteristic that imparts significant therapeutic potential.
      Human embryonic stem cells and induced pluripotent stem cells are types of hPSCs.
      Although hPSCs have high therapeutic potential, their clinical relevance is
      limited by the requirement for animal feeder layers, which maintain their
      pluripotency and self-renewal. hPSCs grown on animal feeder cells are at high
      risk for pathogen contamination and can be affected by the immunogenicity of the
      feeder layer. The presence of animal feeder cells also limits the scalability of
      hPSCs in culture because of the high cost of culturing and batch-to-batch
      variations. Therefore, development of feeder-free systems is imperative for
      robust, lower-cost, xeno-free, scalable culture of hPSCs. Biomaterials engineered
      with bioactive molecules such as adhesion proteins and extracellular matrix
      proteins, or synthetic materials such as peptides and polymers, may provide
      alternative substrates to animal feeder cells. This article reviews biomaterial
      based, feeder-free systems for hPSC growth and maintenance, which provide
      clinically relevant alternatives to feeder cell systems. 

PMID- 24298349
TI  - Delivering factors for reprogramming a somatic cell to pluripotency.
AB  - An adult cell originates from stem cell. The stem cell is usually categorized
      into three species including an embryonic stem cell (ESc), an adult stem cell,
      and an induced stem cell (iPSc). iPSc features pluripotency, which is meant to be
      differentiated into any types of cells. Accordingly, it is much attractive to
      anyone who pursuit a regenerative medicine, owing to the potential almighty. They
      are simply produced by reprogramming a somatic cell via a transfer of
      transcription factors. The efficiency and productivity of iPS are considerably
      subject to delivering methods of exogenous genes into a variety of targeted
      mammalians. Conventional and well-run gene delivery techniques have been reviewed
      here. This details the methods and principles of delivery factors and provides an
      overview of the research, with an emphasis on their potential for use as clinical
      therapeutic platforms. 

PMID- 24298350
TI  - Cancer stem cells in brain tumors and their lineage hierarchy.
AB  - Despite recent advances in the development of novel targeted chemotherapies, the
      prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor
      is attributed to tumor heterogeneity. To explain this unique chemo- resistance,
      the concept of cancer stem cells has been evoked. Cancer stem cells, a
      subpopulation of whole tumor cells, are now regarded as candidate therapeutic
      targets. Here, the author reviews and discusses the cancer stem cell concept. 

PMID- 24298351
TI  - Stimulation of chondrogenic differentiation of mesenchymal stem cells.
AB  - The methods for cartilage repair have been studied so far, yet many of them seem
      to have limitations due to the low regenerative capacity of articular cartilage.
      Mesenchymal stem cell (MSC) has been suggested as an alternative solution to
      remedy this challenging problem. MSCs, which have extensive differentiation
      capacity, can be induced to differentiate into chondrocytes under specific
      conditions. Particularly, this review focused on the effects of growth factors,
      cell-to-cell interactions and biomaterials in chondrogenesis of MSCs. Appropriate
      stimulations through these factors are crucial in differentiation and
      proliferation of MSCs. However, use of MSCs for cartilage repair has some
      drawbacks and risks, such as expression of hypertrophy-related genes in MSCs
      derived chondrocytes and consequent calcification or cell death. Nevertheless,
      the clinical application of MSCs is expected in the future with advanced
      technology. 

PMID- 24298352
TI  - Long-term Angiogenesis Efficacy Using a Heparin-Conjugated Fibrin (HCF) Delivery
      System with HBM-MSCs.
AB  - BACKGROUND AND OBJECTIVES: Heparin-conjugated fibrin (HCF) is suitable for the
      release and localization of bFGF. We analyzed the effects of a bFGF delivery
      system using HCF with human bone marrow-derived mesenchymal stem cells (HBM-
      MSCs) in a dog ischemic limb model. METHODS AND RESULTS: Animals were divided
      into HBM-MSCs, HBM-MSCs+HCF, bFGF-HCF, and HBM-MSCs+ bFGF-HCF groups. A total of
      1*10(7) HBM-MSCs were injected per animal, and the amount of bFGF was 1 mg per
      dog. Ischemic muscles were harvested at eight weeks and six months after
      injection of cells. The HBM-MSCs+ bFGF-HCF group exhibited decreased proportions
      of capillaries and arterioles six months after transplantation. However, there
      were more cells positive for the angiogenic factors, VEGF and PDGF, in the eight
      week specimens compared with those harvested six months after transplantation.
      CONCLUSIONS: Our results demonstrated that a single injection of HBM-MSCs did not
      have significant long-term angiogenic effects; however, a bFGF delivery system
      using HCF exerted prolonged angiogenic effects when combined with HBM-MSCs.

PMID- 24298353
TI  - The levels of pro-inflammatory factors are significantly decreased in cerebral
      palsy patients following an allogeneic umbilical cord blood cell transplant.
AB  - BACKGROUND AND OBJECTIVES: The transplantation of human umbilical cord blood
      cells (hUCBCs) has been shown to attenuate the unregulated activation of
      microglia in a rat model of cerebral palsy (CP). To investigate whether hUCBCs
      transplantation is also anti-inflammatory in humans, we performed a clinical
      trial in patients with CP. METHODS AND RESULTS: Allogeneic or autologous hUCBCs
      and erythropoietin (EPO) were intravenously injected into human patients with CP
      (mean age of approximately 38 weeks), and patients were analyzed for their motor
      function and social behavior. Blood samples were tested for cytokine levels. The
      most surprising finding in the study was that the cytokine levels were dependent
      on the donor cell source (allogeneic or autologous). Interestingly, the
      allogeneic treatment group demonstrated significantly decreased levels of pro
      inflammatory factors, such as IL-1alpha, IL-6, TNF-beta, and RANTES, and showed a
      statistically significant improvement in motor and social behavior compared to
      the autologous treatment group. CONCLUSIONS: Given that inflammation plays a
      pivotal role in CP, our results suggest that allogeneic hUCBCs therapy may be an
      appropriate strategy for CP treatment. In addition, prior to transplantation, a
      detailed analysis of the amount of proinflammatory cytokines in cord blood may be
      needed to avoid exacerbating inflammatory responses.

PMID- 24298355
TI  - Effect of stem cell therapy on induced diabetic keratopathy in albino rat.
AB  - BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (DM) is a prevalent disorder.
      Diabetic keratopathy is a well-known ocular complication secondary to type 2 DM.
      Topical insulin application did not affect apoptosis and necrosis levels in
      corneal epithelium. Autologous cell transplantation is not a viable option for
      diabetic patients with bilateral limbal stem cell deficiency. The present study
      aimed at assessing the possible effect of hemopoeitic stem cell (HSC) therapy on
      induced diabetic keratopathy in albino rat. METHODS AND RESULTS: Fifteen male
      albino rats were divided into control group of 2 rats, diabetic group of 8 rats
      receiving single intraperitoneal (IP) injection of 50 mg/kg streptozotocin (STZ).
      3 animals were sacrificed 6 weeks following confirmation of diabetes to confirm
      keratopathy and 5 rats were sacrificed 4 weeks following confirmation of
      keratopathy. SC therapy group included 5 rats injected with HSCs 6 weeks
      following confirmation of diabetes and sacrificed 4 weeks following SC therapy.
      Cord blood collection, stem cells isolation and labeling were performed. Eye
      specimens were subjected to histological, histochemical, immunohistochemical,
      morphometric and statistical studies. In diabetic group, the central cornea
      showed multiple cells with vacuolated cytoplasm and dark nuclei, focal epithelial
      discontinuity, reduced corneal thickness and less number of layers of corneal and
      conjunctival epithelia. In stem cell therapy group, few cells with vacuolated
      cytoplasm and dark nuclei were found in the corneal and conjunctival epithelia
      with more number of epithelial layers. CONCLUSIONS: A definite ameliorating
      effect of HSC therapy was detected on diabetic keratopathy. The therapeutic cells
      were effective in limiting corneal epithelial changes.

PMID- 24298356
TI  - The Role of PEC Progenitors in ADPKD Progression.
AB  - BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease is a
      pathology mainly characterized by the progressive development and enlargement of
      cysts in each kidneys. Such as many adult epithelial tissue, renal tubule
      replaces damaged or death cells through the presence of stem/progenitor cells
      CD133(+)CD24(+) Obviously, in ADPKD the repair of damages is insufficient to
      block the disease, but renal stem cells could have a role in the pathology. In
      this study we investigate the localization and the involvement of cells
      CD133(+)CD24(+) in ADPKD progression. METHODS AND RESULTS: Two normal kidneys and
      two ADPKD kidneys were examined. CD133 and CD24 expression was investigated by
      confocal microscopy and immunoblotting. Renal tissue and cells were analyzed.
      CD133 and CD24 have the same localization in ADPKD tissues and in normal kidneys:
      a subset of epithelial cells (PEC) of Bowman' s capsule and luminal side of
      tubules. It is interesting that CD133(+) CD24(+) cells are statistically more
      represented in ADPKD tubules (p< 0.001) and in healthy glomeruli (p= 0.0016).
      Cysts express CD133 and CD24. CONCLUSIONS: Renal epithelial progenitors
      demonstrate to be involved in ADPKD pathogenesis but their role will have to be
      clarified and possibly managed to obtain improvement, or at least stabilization,
      of disease.

PMID- 24298354
TI  - Evolution of energy metabolism, stem cells and cancer stem cells: how the warburg
      and barker hypotheses might be linked.
AB  - The evolutionary transition from single cells to the metazoan forced the
      appearance of adult stem cells and a hypoxic niche, when oxygenation of the
      environment forced the appearance of oxidative phosphorylation from that of
      glycolysis. The prevailing paradigm in the cancer field is that cancers start
      from the "immortalization" or "re-programming" of a normal, differentiated cell
      with many mitochondria, that metabolize via oxidative phosphorylation. This
      paradigm has been challenged with one that assumes that the target cell for
      carcinogenesis is the normal, immortal adult stem cell, with few mitochondria.
      This adult organ-specific stem cell is blocked from "mortalizing" or from
      "programming" to be terminally differentiated. Two hypotheses have been offered
      to explain cancers, namely, the "stem cell theory" and the "de-differentiation"
      or "re-programming" theory. This Commentary postulates that the paleochemistry of
      the oceans, which, initially, provided conditions for life' s energy to arise via
      glycolysis, changed to oxidative phosphorylation for life' s processes. In doing
      so, stem cells evolved, within hypoxic niches, to protect the species germinal
      and somatic genomes. This Commentary provides support for the "stem cell theory",
      in that cancer cells, which, unlike differentiated cells, have few mitochondria
      and metabolize via glycolysis. The major argument against the "de-differentiation
      theory" is that, if re-programming of a differentiated cell to an "induced pluri
      potent stem cell" happened in an adult, teratomas, rather than carcinomas, should
      be the result. 

PMID- 24298357
TI  - Treatment of spinal muscolar atrophy with intrathecal mesenchymal cells.
AB  - BACKGROUND AND OBJECTIVES: SMA1 is a genetic disease that leads to a progressive
      apoptosis of the second motoneuron and then to a complete paralysis. There are
      reports of efficacy of mesenchymal cells in the treatment of other neurological
      diseases; therefore we decided to treat some children with these cells. METHODS
      AND RESULTS: Four children suffering from SMA1 were treated by means of
      intrathecal injections of mesenchymal cells. All patients improved their motility
      after three weeks. The effect was relevant at the distal muscles, while the
      proximal ones were less affected. The treatment was repeated once a month for 3~
      8 months as the effect of the treatment lasted not more than 30 days. One patient
      who withdrew the treatment died after 45 days. Another patient resulted
      completely paralysed after two months after quitting the cell therapy but he
      regained the skills after a new injection. Two patients are stable after the
      first improvement. CONCLUSIONS: Intrathecal injections of mesenchymal cells
      improve the motility of children suffering from SMA1. We argue that an early
      treatment, before the onset of irreversible neurological damages, could result in
      the cure of this disease.

PMID- 24298358
TI  - Clinical response of 277 patients with spinal cord injury to stem cell therapy in
      iraq.
AB  - BACKGROUND AND OBJECTIVES: Spinal cord injury is a common neurological problem
      secondary to car accidents, war injuries and other causes, it may lead to varying
      degrees of neurological disablement, and apart from physiotherapy there is no
      available treatment to regain neurological function loss. Our aim is to find a
      new method using autologous hematopoietic stem cells to gain some of the
      neurologic functions lost after spinal cord injury. METHODS AND RESULTS: 277
      patients suffering from spinal cord injury were submitted to an intrathecally
      treatment with peripheral stem cells. The cells were harvested from the
      peripheral blood after a treatment with G-CSF and then concentrated to 4~ 6 ml.
      43% of the patients improved; ASIA score shifted from A to B in 88 and from A to
      C in 32. The best results were achieved in patients treated within one year from
      the injury. CONCLUSIONS: Since mesenchymal cells increase in the peripheral blood
      after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than
      mesenchymal cell cultivation prior to injection. It seems reasonable treatment
      for spinal cord injury.

PMID- 24298359
TI  - In vivo Tracking of Human Neural Stem Cells Following Transplantation into a
      Rodent Model of Ischemic Stroke.
AB  - BACKGROUND AND OBJECTIVES: Ischemic stroke caused by middle cerebral artery
      occlusion (MCAo) is the major type of stroke, but there are currently very
      limited options for cure. It has been shown that neural stem cells (NSCs) or
      neural precursor cells (NPCs) can survive and improve neurological deficits when
      they are engrafted in animal models of various neurological diseases. However,
      how the transplanted NSCs or NPCs are act in vivo in the injured or diseased
      brain is largely unknown. In this study, we utilized magnetic resonance imaging
      (MRI) techniques in order to understand the fates of human NSCs (HB1.F3)
      following transplantation into a rodent model of MCAo. METHODS AND RESULTS:
      HB1.F3 human NSCs were pre-labeled with ferumoxides (Feridex((r)))-protamine
      sulfate complexes, which were visualized and examined by MRI up to 9 weeks after
      transplantation. Migration of the transplanted cells to the infarct area was
      further confirmed by histological methods. CONCLUSIONS: Based on these
      observations, we speculate that the transplanted NSCs have the extensive
      migratory ability to the injured site, which will in turn contribute to
      functional recovery in stroke.

PMID- 24298360
TI  - Enactment of a law for governmental support of the use of cord blood, and ethical
      issues.
AB  - In Korea, cord blood banking projects have been developed since 1996, and the 1st
      successful cord blood transplant was performed in 1998. Recently, "Cord Blood
      Management and Research Act" was legislated in 2010, and has been come into
      effect on July 1st, 2011. This review focuses the backgrounds, aims, and
      legislation process as well as principal articles in this act. 

PMID- 24298361
TI  - Do the Fibroblasts Contained in Early Passage MSC Population Adversely Affect the
      Characteristics of Stem Cell Population Obtained from Human Placenta?
AB  - BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) have been obtained from
      various human tissues by harvesting plastic adherent fibroblast-like cell
      population. For potential use in regeneration medicine, early passage MSC
      population is preferred to avoid cell senescence. The early passage adherent cell
      population contains MSCs as well as fibroblasts, however, the significance of the
      contained fibroblasts has not been well investigated. Thus, we investigated the
      stem cell characteristics of the early passage MSC population with and without
      fibroblasts depletion. METHODS AND RESULTS: We obtained adherent cell populations
      from full term placenta at passage 2~3 and divided them into two subpopulations:
      fibroblasts depleted (popFD) and non-depleted population (popFND) using magnetic
      cell sorting method. The two subpopulations were compared in terms of cell
      morphology, potential for long term culture, colony forming ability, and tri
      lineage differentiation for adipogenic, chondrogenic, and osteogenic
      differentiation. The percentage of fibroblasts contained in the early passage MSC
      population was 5.3% (2.9~8.4). Both the popFD and popFND was spindle shaped from
      early passages and maintained long term culture up to 20~22 passages. CFU-F assay
      showed no difference between the subpopulations. Overall, tri-lineage
      differentiation showed a tendency of better differentiation potential of popFND
      than popFD. CONCLUSIONS: We confirmed that fibroblasts are contained in early
      population of placenta-derived MSCs obtained by current method. This study
      revealed that the contained fibroblasts in early passage MSC population do not
      adversely affect the properties of MSCs in terms of cell morphology, potential
      for long term culture, colony forming ability, and tri-lineage differentiation.

PMID- 24298362
TI  - Effects of Growth Factors on Establishment and Propagation of Embryonic Stem
      Cells from Very Early Stage IVF Embryos and Their Characterization in Buffalo.
AB  - BACKGROUND AND OBJECTIVES: Although ES cells have been derived from very early
      stage embryos in different species, but, so far ES cell line could be derived
      from early stage IVF embryos in buffalo. The present experiment was carried out
      to study the effects of different growth factors on attachment, formation of ES
      cell colonies, their extent of passaging and relative expression of pluripotency
      marker in these colonies in buffalo. METHODS AND RESULTS: For this, 8~16 cell
      stages zona free IVF embryos were cultured with different culture condition viz.
      Control, Media-I: (Control+SCF), Media-II: (Control+SCF+bFGF) and Media-III:
      (Control+SCF+bFGF+IGF1). A total of 25 number of embryos were cultured in each
      medium. The efficiency (%) of blastomere attachment, % stem cell colony formation
      were recorded and number of passaging were evaluated in each culture condition.
      The results indicated that the efficiency of embryonic blastomere attachment, %
      stem cell colonies formation and propagation were significantly higher when
      medium was supplemented with growth factors viz. SCF, bFGF and IGF-1 (Media-III)
      than when supplemented with either SCF or SCF+bFGF. The expression of pluripotent
      genes viz Oct4, Nanog, FoxD3 and KLF4 were significantly higher (p<0.005) when
      medium was supplemented with three growth factors. CONCLUSIONS: It can be
      concluded that when 8~16 cell stages zona free IVF embryos of buffalo was
      cultured on feeder,the %of blastomere attachment, % of ES cell colony formation
      and their further propagation were higher in ES cell medium supplemented with
      SCF+bFGF+IGF1 which may be due to high expression of pluripotent stem cell
      markers.

PMID- 24298363
TI  - Adipose stem cells as alternatives for bone marrow mesenchymal stem cells in oral
      ulcer healing.
AB  - BACKGROUND AND OBJECTIVES: Adipose tissue is now recognized as an accessible,
      abundant, and reliable site for the isolation of adult stem cells suitable for
      tissue engineering and regenerative medicine applications. METHODS AND RESULTS:
      Oral ulcers were induced by topical application of formocresol in the oral cavity
      of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow
      Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was
      injected around the ulcer in each group. The healing process of the ulcer was
      monitored clinically and histopathologically. Gene expression of vascular
      endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription
      Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was
      detected in biopsies from all ulcers. RESULTS: MSCs expressed mRNA for VEGF MSCs
      transplantation significantly accelerated oral ulcer healing compared with
      controls. There was increased expression of both collagen and VEGF genes in MSCs
      treated ulcers compared to controls. CONCLUSIONS: MSCs transplantation may help
      to accelerate oral ulcer healing, possibly through the induction of angiogenesis
      by VEGF together with increased intracellular matrix formation as detected by
      increased collagen gene expression. This body of work has provided evidence
      supporting clinical applications of adipose-derived cells in safety and efficacy
      trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer
      healing.

PMID- 24298364
TI  - Tissue regeneration and stem cell distribution in adriamycin induced
      glomerulopathy.
AB  - BACKGROUND AND OBJECTIVES: Glomerulosclerosis develops secondary to various
      kidney diseases. It was postulated that adriamycin (ADR) induce chronic
      glomerulopathy. Treatment combinations for one year did not significantly modify
      renal function in resistant focal segmental glomerulosclerosis (FSGS). Recurrence
      of FSGS after renal transplantation impacts long-term graft survival and limits
      access to transplantation. The present study aimed at investigating the relation
      between the possible therapeutic effect of human mesenchymal stem cells (HMSCs),
      isolated from cord blood on glomerular damage and their distribution by using ADR
      induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty
      three male albino rats were divided into control group, ADR group where rats were
      given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were
      sacrificed 10, 20 and 30 days following confirmation of glomerular injury. In
      stem cell therapy group, rats were injected with HMSCs following confirmation of
      renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney
      sections were exposed to histological, histochemical, immunohistochemical,
      morphometric and serological studies. In response to SC therapy multiple
      Malpighian corpuscles (MC) appeared with patent Bowman's space (Bs) 10 and 20
      days following therapy. One month following therapy no remarkable shrunken
      glomeruli were evident. Glomerular area and serum creatinine were significantly
      different in ADR group in comparison to control and SC therapy groups.
      CONCLUSIONS: ADR induced glomerulosclerosis regressed in response to cord blood
      HMSC therapy. A reciprocal relation was recorded between the extent of renal
      regeneration and the distribution of undifferentiated mesenchymal stem cells.

PMID- 24298365
TI  - SIRT1 Inhibits p53 but not NF-kappaB Transcriptional Activity during
      Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.
AB  - BACKGROUND AND OBJECTIVES: SIRT1, a histone diacetylase, modify transactivation
      function of various transcription factor including p53 and NF-kappaB. p53 and NF
      kappaB is involved in in vitro differentiation of mouse embryonic stem cells
      (mESC) into mouse embryoid body (mEB). These suggest that SIRT1 might affect in
      vitro differentiation of mESC into mEB by regulation of p53 and NF-kappaB.
      METHODS AND RESULTS: In this study we analyzed the effect of SIRT1 in in vitro
      differentiation of mESC into mEB using wild and SIRT1 knockout mESC. To examine
      SIRT1-specific gene in mESC, this study conducted microarray-based differential
      gene expression analysis between wild and SIRT1 knockout mESC. Comparing their
      gene expression patterns, this study determined a list of genes regulated by
      SIRT1. cDNA microarray data-set analysis revealed that genes associated with
      transcription and signal transduction are significantly modified in SIRT1
      knockout mESC. cDNA microarray data-set analysis between mESC and EB in wild and
      SIRT1 showed that SIRT1 inhibits p53 signaling pathway but not affect NF-kappaB
      signaling pathway. CONCLUSIONS: This study suggests that SIRT1 modify mESC
      differentiation by regulation of p53 transcriptional activity.

PMID- 24298366
TI  - Effect of stem cell therapy on adriamycin induced tubulointerstitial injury.
AB  - BACKGROUND AND OBJECTIVES: It was postulated that adriamycin (ADR) induce renal
      tubulointerstitial injury. Clinicians are faced with a challenge in producing
      response in renal patients and slowing or halting the evolution towards kidney
      failure. The present study aimed at investigating the relation between the
      possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated
      from cord blood on tubular renal damage and their distribution by using ADR
      induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty
      three male albino rats were divided into control group, ADR group where rats were
      given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were
      sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem
      cell therapy group, rats were injected with HMSCs following confirmation of renal
      injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections
      were exposed to histological, histochemical, immunohistochemical, morphometric
      and serological studies. In response to SC therapy, vacuolated cytoplasm, dark
      nuclei, detached epithelial lining and desquamated nuclei were noticed in few
      collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of
      CT showing desquamated nuclei and mean value of serum creatinine revealed
      significant difference in ADR group. The mean area% of Prussian blue+ve cells and
      that of CD105 +ve cells measured in subgroup S1 denoted a significant increase
      compared to subgroups S2 and S3. CONCLUSIONS: ADR induced tubulointerstitial
      damage that regressed in response to cord blood HMSC therapy.

PMID- 24298367
TI  - Neuronal Differentiation of a Human Induced Pluripotent Stem Cell Line (FS-1)
      Derived from Newborn Foreskin Fibroblasts.
AB  - Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated
      somatic cells has revolutionized existing concepts of cell differentiation and
      stem cells. Importantly, iPSCs generated from somatic cells of patients can be
      used to model different types of human diseases. They may also serve as
      autologous cell sources that can be used in transplantation therapy. In this
      study, we investigated the neuronal properties of an iPSC line that is derived
      from human neonatal foreskin fibroblasts (FS-1). We initially examined the
      morphology and marker expression of FS-1 cells at undifferentiated stage. We then
      spontaneously differentiated FS-1 cells in suspension culture and examined the
      expression of markers representing three germ layers. We finally differentiated
      FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells,
      and found that, under the conditions we used, they have a tendency to
      differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived
      neural cells will be useful to be used in cell therapy of stroke or Huntington's
      disease, among others. Taken together, FS-1 cells derived from human neonatal
      fibroblasts exhibit very similar properties with human ES cells, and can provide
      useful sources for cell therapy and various other applications. 

PMID- 24298368
TI  - Clinical neurofunctional rehabilitation of a cat with spinal cord injury after
      hemilaminectomy and autologous stem cell transplantation.
AB  - Stem cell-based therapy has been investigated in a number of degenerative and
      traumatic diseases, including spinal cord injury. In the present study, we
      investigated the use of autologous mesenchymal stem cells in the functional
      rehabilitation of a domestic cat presenting a compressive L1-L5 fracture. Bone
      marrow cells collected by puncture of the iliac crest were cultured to obtain
      mesenchymal stem cells three weeks before surgery. Hemilaminectomy was performed,
      followed by injection of the mesenchymal stem cells in the injured area. Clinical
      evaluation of the animal prior to surgery showed absence of pain, muscular tonus,
      and panniculi reflexes. Seven days after surgery and cell transplantation the
      examination revealed a progressive recovery of the panniculus reflexes and of the
      responses to superficial and deep pain stimuli despite the low proprioceptive and
      hyperreflexic ataxic hind limbs. Physiotherapy protocols were applied for
      clinical rehabilitation after surgery. The cat's first steps, three-minute weight
      bearing, and intestine and urinary bladder partial reestablishment were observed
      75 days post-surgery. Our results indicate the therapeutic potential of
      mesenchymal stem cells in chronic spinal cord injuries. 

PMID- 24298369
TI  - The effect of in vivo mobilization of bone marrow stem cells on the pancreas of
      diabetic albino rats (a histological & immunohistochemical study).
AB  - BACKGROUND AND OBJECTIVES: The rapidly increasing number of diabetic patients
      across the world drew the attention to develop more effective therapeutic
      approaches. Recent investigations on newly differentiated insulin producing cells
      (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and
      hematopoietic stem cells. This work was planned to evaluate the role of
      StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing
      naturally occurring bone marrow stem cells as well as in improving streptozotocin
      induced diabetic rats. METHODS AND RESULTS: Twenty adult male albino rats were
      divided into four groups namely the control, the diabetic, the positive control
      StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by
      streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number
      of blood CD34 immunopositive cells was measured by flowcytometry and random blood
      sugar was measured weekly. The pancreas was removed from the sacrificed rats and
      processed for staining with H&E and immunohistochemical staining for CD34+ve and
      insulin +ve cells. CD34+ve cells increased in the blood after introduction of
      StemEnhance. CD34+ve cells were observed in the pancreas and the insulin
      producing cells in the islets of Langerhans were increased from the second to the
      fourth week of treatment. Blood glucose level improved but it was still higher
      than the control level after four weeks of StemEnhance treatment. CONCLUSIONS:
      This work points to the significant role of StemEnhance in stem cell mobilization
      and the improvement of diabetes mellitus.

PMID- 24298370
TI  - Effect of bone marrow derived mesenchymal stem cells on healing of induced full
      thickness skin wounds in albino rat.
AB  - BACKGROUND AND OBJECTIVES: Mesenchymal stem cells have delivered new approaches
      to the management of wound healing in severe skin injuries. This work was planned
      to evaluate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on
      healing of induced full thickness skin wounds in albino rats using topical &
      systemic injections. METHODS AND RESULTS: Forty adult male albino rats were
      classified into 2 groups after induction of full thickness skin wound; untreated
      group and stem cell-treated group. The latter was further subdivided into
      topically and systemically treated ones. BMSCs were isolated & labeled by PKH26
      before injection. Healing of wounds was evaluated grossly. Skin biopsies were
      obtained one & three weeks after wound induction. Sections were stained with
      Hematoxylin & Eosin, Masson's trichrome and immunohistochemichal stain for
      vascular endothelial growth factor (VEGF). Epidermal thicknesses and mean area
      percent of both collagen fibers & VEGF immunopositive cells were measured using
      image analyzer & results were subjected to statistical analysis. PKH26
      fluorescent-labeled cells were found in the regenerated epidermis, hair follicles
      and dermis in BMSCs-treated groups. By the end of the third week, the wounds of
      BMSCs-treated groups showed full regeneration of epidermis, re-organization of
      collagen and decrease in VEGF immunopositive cells. Delayed wound healing was
      seen in 20% of systemically treated rats. Significant increase in the mean area
      percent of collagen fibers was detected in topically treated group. CONCLUSIONS:
      Both methods of BMSCs injection were effective in healing of full thickness skin
      wound but topical method was more effective.

PMID- 24298371
TI  - Developmental Competence of Buffalo (Bubalus bubalis) Pluripotent Embryonic Stem
      Cells Over Different Homologous Feeder Layers and the Comparative Evaluation with
      Various Extracellular Matrices.
AB  - BACKGROUND AND OBJECTIVES: Use of somatic cells as a feeder layer to maintain the
      embryonic stem cells (ESCs) in undifferentiated state limits the stem cell
      research design, since experimental data may result from a combined ESCs and
      feeder cell response to various stimuli. Therefore, present study was designed to
      evaluate the developmental competence of the buffalo ESCs over different
      homogenous feeders and compare with various extracellular matrices using
      different concentrations of LIF. METHODS AND RESULTS: Inner cell masses (ICMs) of
      in vitro hatched blastocysts were cultured onto homologous feeders viz. fetal
      fibroblast, granulosa and oviductal cell feeder layers and synthetic matrices
      viz. fibronectin, collagen type I and matrigel in culture medium. Developmental
      efficiency was found higher for ESCs cultured on fetal fibroblast and granulosa
      layers (83.33%) followed by fibronectin (77.78%) at 30 ng LIF. Oviductal feeder
      was found to be the least efficient feeder showing only 11.11% undifferentiated
      primary ESC colonies at 30 ng LIF. However, neither feeder layer nor synthetic
      matrix could support the development of primary colonies at 10 ng LIF. Expression
      of SSEA- 4, TRA-1-60 and Oct-4 were found positive in ESC colonies from all the
      feeders and synthetic matrices with 20 ng and 30 ng LIF. CONCLUSIONS: Fetal
      fibroblast and granulosa cell while, amongst synthetic matrices, fibronectin were
      found to be equally efficient to support the growth and maintenance of ESCs
      pluripotency with 30 ng LIF. This well-defined culture conditions may provide an
      animal model for culturing human embryonic stem cells in the xeno-free or feeder
      free conditions for future clinical applications.

PMID- 24298372
TI  - A phase I study of human cord blood-derived mesenchymal stem cell therapy in
      patients with peripheral arterial occlusive disease.
AB  - BACKGROUND AND OBJECTIVES: Half of patients with critical limb ischemia (CLI) are
      ineligible for revascularization at diagnosis. The aim of this study was to
      assess the safety and feasibility of intramuscular human umbilical cord blood
      derived mesenchymal stem cell (hUCB-MSC) therapy in patients with CLI due to
      atherosclerosis obliterans (ASO) or thromboangiitis obliterans (TAO). METHODS AND
      RESULTS: A total of eight patients (all male, median age 52 years, range 31~77)
      with CLI were enrolled in this phase I trial. All patients were considered
      ineligible for further revascularization to improve CLI. We injected 1*10(7) hUCB
      MSCs per single dose intramuscularly into the affected limb. The primary end
      points of safety were occurrence of adverse events (procedure-related
      complication, allergic reaction to hUCB-MSCs, graft-versus-host disease,
      cardiovascular and cerebrovascular events) and improvement of symptoms/clinical
      parameters (healing of foot ulcer, ankle-brachial index, and pain-free walking
      distance). Angiogenesis was measured with conventional angiography and scored by
      an independent reviewer. There were four adverse events in three patients. One
      patient, developed whole body urticaria after injection on treatment day, which
      disappeared after one day of antihistamine treatment. The other adverse events
      included diarrhea, oral ulceration, and elevation of serum creatinine level; all
      conditions improved without treatment. Abnormal results of laboratory parameters
      were not detected in any patients. Three of four ulcerations (75%) healed
      completely. Angiographic scores increased in three of eight patients.
      CONCLUSIONS: This phase I study demonstrates that intramuscular hUCB-MSC
      injection is a safe and well tolerated treatment for patients with end-stage CLI
      due to ASO and TAO.

PMID- 24298373
TI  - New approach of bone marrow-derived mesenchymal stem cells and human amniotic
      epithelial cells applications in accelerating wound healing of irradiated albino
      rats.
AB  - BACKGROUND AND OBJECTIVES: Irradiated wound healing is a highly complex and
      dynamic process. The latest technology making a huge difference in this process
      is stem cell therapy. The goal of this study was to evaluate the use of bone
      marrow-derived mesenchymal stem cells (BM-MSCs) or human amniotic epithelial
      cells (HAECs) in the healing of irradiated wounds. METHODS AND RESULTS: Forty
      five male albino rats were subjected to whole body 6 gray gamma radiations. One
      day post irradiation, full-thickness incisional wound was created in the tibial
      skin. The rats were randomly equally divided into three groups. The incisions of
      the first group (gp I) were injected intra-dermally with saline before stitching
      and those of both the second (gp II) and the third groups (gp III) were
      intradermally injected with BM-MSCs and HAECs before stitching respectively.
      Animals were sacrificed after the third, seventh and fourteenth days
      postoperative. The healing process was assessed histopathologically. CXCL-5, SDF
      1 and Transforming growth factor-beta 1 (TGF-beta1) expression were also detected
      in biopsies from all wounds. Expression of TGF-beta1 in gp I was more than the
      other groups leading to severe inflammation, deficient healed dermis and delayed
      reepithelialization. SDF-1 expression was high in gp II while CXCL-5 expression
      was high in gp III causing accelerated wound healing. BM-MSCs showed a great
      effect on the quality of the dermis, while superiority of the epithelium and its
      appendages were achieved in HAECs group. CONCLUSIONS: Using BM-MSCs and HAECs
      could be used safely in case of irradiated wounds.

PMID- 24298374
TI  - Histological study on effect of mesenchymal stem cell therapy on experimental
      renal injury induced by ischemia/reperfusion in male albino rat.
AB  - BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) represents a major clinical
      problem with high mortality and limited treatment protocols. This study was
      planned to evaluate the therapeutic effectiveness of bone marrow - derived
      mesenchymal stem cells (BM-MSCs) in a rat model of ischemia/reperfusion (I/R)
      AKI. METHODS AND RESULTS: This study was carried out on thirty adult male albino
      rats. Animals were divided equally into three groups. Group I (control sham
      operated group) (n=10), were subdivided equally into two subgroups; Ia and Ib.
      The experimental group (n=20) were all subjected to I/R injury by clamping both
      renal pedicles for 40 minutes. Half of the I/R animals did not receive MSC
      therapy (group II) [non-MSC treated group]. The other half of the I/R animals
      received single intravenous injection of PKH26 labelled BM-MSCs immediately after
      removal of the clamps and visual confirmation of reflow (group III) [MSC treated
      group]. Animals were sacrificed 24 hrs (subgroups IIa & IIIa) and 72 hrs
      (subgroups IIb & IIIb) after intervention. Serological measurements included
      serum urea and creatinine. Kidney specimens were processed for H&E, PAS and PCNA.
      Mean % of renal corpuscles with affected glomeruli, mean % of affected tubules,
      mean area % of PAS-positive reaction and mean area % of PCNA immunoreactivity
      were measured by histomorphometric studies and statistically compared. MSCs
      treated group exhibited protection against renal injury serologically and
      histologically. CONCLUSIONS: Results of the present study suggest a potential
      reno-protective capacity of MSCs which could be of considerable therapeutic
      promise for cell-based management of clinical AKI.

PMID- 24298375
TI  - Osteogenic Differentiation of Bone Marrow Stem Cell in Poly(Lactic-co-Glycolic
      Acid) Scaffold Loaded Various Ratio of Hydroxyapatite.
AB  - BACKGROUND AND OBJECTIVES: Hydroxyapatite has biocompatibility and bioactivity
      and similar to bone of in human body. The purpose of this study is to evaluate
      osteogenic differentiation of bone marrow stem cell (BMSC) in PLGA Scaffold added
      various ratio of hydroxyapatite (HAp). METHODS AND RESULTS: PLGA and PLGA/HAp
      scaffold were prepared using solvent casting/salt-leaching method. BMSC was
      seeded on the PLGA and PLGA/HAp scaffold and the samples were cultured in 37C
      incubator with 5% CO2 for 28 days. Alkaline phosphatase (ALP) was carried out to
      evaluate alkaline phosphatase activity at 1, 3, 7, 10 and 14 days. Alizarin Red S
      stating was performed to identify calcium in scaffold at 1, 7, 14, 21 and 28
      days. Compressive strength was measured to evaluate mechanical property of
      scaffold. To confirm cell viability, MTT was carried out at 1, 3, 7, 14 and 28
      days. RT-PCR was performed to verify specific marker expression of osteoblast and
      stem cell at 7, 14, 21 and 28 days. CONCLUSIONS: Osteogenic differentiation of
      BMSC was confirmed through ALP, RT-PCR, and alizarin red S staining in this
      study. These results suggest that HAp helps osteogenic differentiation of BMSC.

PMID- 24298376
TI  - Isolation and characterization of the progenitor cells from the blastema tissue
      formed at experimentally-created rabbit ear hole.
AB  - Objective(s) : Throughout evolution, mammalians have increasingly lost their
      ability to regenerate structures however rabbits are exceptional since they
      develop a blastema in their ear wound for regeneration purposes. Blastema
      consists of a group of undifferentiated cells capable of dividing and
      differentiating into the ear tissue. The objective of the present study is to
      isolate, culture expand, and characterize blastema progenitor cells in terms of
      their in vitro differentiation capacity. MATERIALS AND METHODS: Five New Zealand
      white male rabbits were used in the present study. Using a punching apparatus, a
      4-mm hole was created in the animal ears. Following 4 days, the blastema ring
      which was created in the periphery of primary hole in the ears was removed and
      cultivated. The cells migrated from the blastema were expanded through 3
      successive subcultures and characterized in terms of their potential
      differentiation, growth characteristics, and culture requirements. RESULTS: The
      primary cultures tended to be morphologically heterogeneous having spindly-shaped
      fibroblast-like cells as well as flattened cells. Fibroblast-like cells survived
      and dominated the cultures. These cells tended to have the osteogenic,
      chondrogenic, and adipogenic differentiation potentials. They were highly
      colonogenic and maximum proliferation was achieved when the cells were plated at
      density of 100 cells/cm2 in a medium which contained 10% fetal bovine serum
      (FBS). CONCLUSION: Taken together, blastema tissue-derived stem cells from rabbit
      ear are of mesenchymal stem cell-like population. Studies similar to this will
      assist scientist better understanding the nature of blastema tissue formed at
      rabbit ear to regenerate the wound.

PMID- 24298377
TI  - Differential consequences of unilateral nasal air-puff stimulation on breathing
      pattern and respiratory system mechanics in tracheotomized rats.
AB  - OBJECTIVE(S): Reflexes that rose from mechanoreceptors in nasal cavities have
      extensive neuro-regulatory effects on respiratory system. Because of side
      specific geometry and dual innervations of the nasal mucosa, we investigated the
      consequences of unilateral nasal stimulations on respiratory mechanics and
      breathing patterns. MATERIALS AND METHODS: Unilateral nasal air-puff stimulation
      (30 min) in the presence of propranolol (25 mg/kg) and atropine (5 mg/kg) were
      applied on tracheotomized spontaneously breathing rats. Breathing rate and
      pattern monitored. Peak inspiratory pressure (PIP) and flow (PIF) were exploited
      for calculation of resistance, dynamic compliance (Cdyn), and estimation of
      respiratory system impedance (Zrs). RESULTS: During right-side stimulation, in
      propranolol (P<0.05) and atropine groups (P<0.01) PIP significantly decreased in
      comparison to the control group. Alternatively, it significantly increased in
      left-side and propranolol-left groups (P<0.05) than control group. Mean Cdyn
      following left-side stimulation and propranolol, revealed significant decrements
      (P<0.05) than control group. In the case of atropine-right and atropine-left
      groups, mean Cdyn had significantly decreased in comparison with atropine alone
      (P<0.05). Airway resistance (R) did not reveal significant difference during
      nasal stimulations whereas least square approximation revealed a significant side
      specific frequency dependent deviation of imaginary part of impedance (X). An
      inverse correlation was determined for Cdyn versus frequency following right side
      (R=-0.76) and left side (R=-0.53) stimulations. CONCLUSION: For the reason that
      lower airways mechanics changed in a way independent from smooth muscle, it may
      be concluded from our data that unilateral nasal stimulations exert their
      different controls through higher regulatory centers.

PMID- 24298378
TI  - The Relaxant Effects of Different Methanolic Fractions of Nigella sativa on
      Guinea Pig Tracheal Chains.
AB  - OBJECTIVE(S): In regard to the high incidence of asthma and the side-effects of
      the drugs used, finding novel treatments for this disease is necessary. Our
      previous studies demonstrated the preventive effect of Nigella sativa extract on
      ovalbumin-induced asthma. In addition, water-soluble substances of N. sativa
      extract and methanol fraction of this plant were responsible for the relaxant
      effect of this plant on tracheal chains of guinea pigs. Therefore, for the first
      time, in the present study, in order to identify main constituents of the
      methanolic extract, the relaxant effects of five different methanolic fractions
      (20%, 40%, 60%, 80%, and 100%) of N. sativa on tracheal chains of guinea pigs
      were examined. MATERIALS AND METHODS: The relaxant effects of four cumulative
      concentrations of each fraction (0.8, 1.2, 1.6, and 2.0 g%) in comparison with
      saline as negative control and four cumulative concentrations of theophylline
      (0.2, 0.4, 0.6, and 0.8 mM) were examined by their relaxant effects on
      precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 uM
      methacholine (group 2). RESULTS: In group 1, all concentrations of only
      theophylline showed significant relaxant effects but all concentrations of these
      methanolic fractions showed significant contractile effects compared with that of
      saline (P<0.001 to P<0.05). However, in group 2, all concentrations of
      theophylline and these methanolic fractions showed significant relaxant effects
      compared with that of saline (P<0.001 to P<0.05). CONCLUSION: These results
      showed a potent relaxant effect of 20% methanolic fractions from N. sativa on
      tracheal chains of guinea pigs that were higher than that of theophylline at the
      used concentrations.

PMID- 24298379
TI  - The Role of Capsaicin-induced Acute Inactivation of C-fibers on Tactile Learning
      in Rat.
AB  - OBJECTIVE(S): In our previous study, we reported that capsaicin-induced
      unmyelinated C-fiber depletion can modulate excitatory and integrative circuits
      in the somatosensory cortex following experience-dependent plasticity. In this
      study, we investigated the involvement of the capsaicin-induced acute
      inactivation of c-fibers on tactile learning in rat. MATERIALS AND METHODS: The
      delayed novel object recognition test was used to assess tactile learning. This
      procedure consisted of two phases. The first of these (T1) was a training phase
      during which the animals explored two similar objects. T2, the test phase,
      occurred 24 hr later, during which the animals explored one novel and one
      familiar object. In order to induce acute inactivation of the C-fiber pathway, 25
      30 MUl of a 10% capsaicin was injected subcutaneously into the rat's upper lip, 6
      h prior to T1. Tactile learning was quantified using a discrimination ratio.
      RESULTS: In T2, the discrimination ratio in capsaicin-treated animals (37.3+/
      3.8%) was lower than that observed in vehicle-treated animals (54.4+/-5.1%,
      P<0.05). CONCLUSION: These findings indicate that the selective inactivation of a
      peripheral nociceptor subpopulation affects tactile learning.

PMID- 24298380
TI  - Improvement of Expression of alpha6 and beta1 Integrins by the Co-culture of
      Adult Mouse Spermatogonial Stem Cells with SIM Mouse Embryonic Fibroblast Cells
      (STO) and Growth Factors.
AB  - OBJECTIVE(S): Spermatogonial Stem Cells (SSCs) maintain spermatogenesis
      throughout the life of the male. Because of the small number of SSCs in adult,
      enriching and culturing them is a crucial step prior to differentiation or
      transplantation. Maintenance of SSCs and transplantation or induction of in vitro
      spermio-genesis may provide a therapeutic strategy to treat male infertility.
      This study investigated the enrichment and proliferation of SSCs co-cultured with
      STO cells in the presence or absence of growth factors. MATERIALS AND METHODS:
      Spermatogonial populations were enriched from the testis of 4-6 week-old male
      mice by MACS according to the expression of a specific marker, Thy-1. Isolated
      SSCs were cultured in the presence or absence of growth factors (GDNF, GFRalpha1
      and EGF) on STO or gelatin-coated dishes for a week. Subsequently, the authors
      evaluated the effects of growth factors and STO on SSCs colonization by alkaline
      phosphates (AP) activity and flow cytometery of alpha6 and beta1 integrins.
      RESULTS: SSCs co-cultured with STO cells and growth factors developed
      colonization and AP activity as well as expression of alpha6 and beta1 integrins
      (P<=0/05). CONCLUSION: Our present SSC-STO co-culture provides conditions that
      may allow efficient maintenance and proliferation of SSCs for the treatment of
      male infertility.

PMID- 24298381
TI  - HLA Class I Allele Frequencies in Southern Iranian Women with Breast Cancer.
AB  - OBJECTIVE(S): Breast cancer is the leading cause of cancer-related death in women
      worldwide. It has been revealed that elevated risk for malignancy may be
      associated with certain HLA alleles. This study was performed to assess the
      association of HLA class I alleles with breast cancer in women in Southern Iran.
      MATERIALS AND METHOD: Eighty nine patients included for analyzing the HLA class I
      alleles frequency using complement dependent cytotoxicity microassay and results
      were compared to 86 gender-matched healthy volunteers. RESULTS: There were
      significantly more patients with A24(9) allele than those of healthy individuals
      (38.2% versus 16.3%) (P-value=0.002). In contrast, HLA-A1 had significantly much
      less expression in the patient group compared to the controls (P- value=0.04).
      CONCLUSION: A24(9) allele appears to be one of the factors increasing an
      individual's the susceptibility to breast cancer in our population but further
      investigation might be required.

PMID- 24298382
TI  - Neuroprotective consequences of postconditioning on embolic model of cerebral
      ischemia in rat.
AB  - OBJECTIVE(S): It has been reported that ischemic postconditioning, conducted by a
      series of brief occlusion and release of the bilateral common carotid arteries,
      confers neuroprotection in permanent or transient models of stroke. However,
      consequences of postconditioning on embolic stroke have not yet been
      investigated. MATERIALS AND METHODS: In the present study, rats were subjected to
      embolic stroke (n=30) or sham stroke (n=5). Stroke animals were divided into
      control (n=10) or three different patterns of postconditioning treatments (n=20).
      In the first pattern of postconditioning (PC10, n=10), the common carotid
      arteries (CCA) were occluded and reopened 10 and 30 sec, respectively for 5
      cycles. Both occluding and releasing times in pattern 2 (PC30, n=5) and 3 (PC60,
      N=5) of postconditionings, were five cycles of 30 or 60 sec, respectively.
      Postconditioning was induced at 30 min following the stroke. Subsequently,
      cerebral blood flow (CBF) was measured from 5 min before to 60 min following to
      stroke induction. Infarct size, brain edema and neurological deficits and
      reactive oxygen species (ROS) level was measured two days later. RESULTS: While
      PC10 (P<0.001), PC30 and PC60 (P<0.05) significantly decreased infarct volume,
      only PC10 decreased brain edema and neurological deficits (P<0.05).
      Correspondingly, PC10 prevented the hyperemia of brain at 35, 40, 50 and 60 min
      after the embolic stroke (P<0.005). No significant difference in ROS level was
      observed between PC10 and control group. CONCLUSION: Ischemic postconditioning
      reduces infarct volume and brain edema, decreases hyperemia following to injury
      and improves neurological functions after the embolic model of stroke.

PMID- 24298383
TI  - The effect of cationic charge density change on transfection efficiency of
      polyethylenimine.
AB  - OBJECTIVE(S): Polyethylenimine (PEI) is a potent non-viral gene delivery carrier.
      PEI surface charge plays a major role in its condensation ability which in turn
      is a necessary requirement for high transfection efficiency. As the PEI charge
      density is dependent on pH, the effect of pH changing PEI on PEI condensation
      ability, transfection efficiency, and cytotoxicity was investigated. MATERIALS
      AND METHODS: In order to compare the different values of pH, 25 kDa PEI solutions
      were prepared at the pH values of 5, 7 and 10, afterward complexed with two
      plasmids encoding reporter genes of luciferase and enhanced green fluorescence
      protein to evaluate the capability of polymers in plasmid delivery at two
      incubation time (4 versus 24 hr). RESULTS: The condensation ability of PEI in
      acidic, neutral and basic environments was similar. At low pH value, the polyplex
      had negative surface charge whereas at a higher pH value, the surface charge
      increased and became positive. The higher transfection efficiency and lower
      cytotoxicity were achieved by the polyplexes prepared at the pH value of 5 with
      longer incubation time of 24 hr. CONCLUSION: The results showed the impact of pH
      value of PEI on biological and biophysical properties of polyplexes. Although the
      proton sponge effect can justify several properties of PEI, these results suggest
      that the proton sponge hypothesis may not be applicable for polymers with low
      buffering capacity at the pH values around 5.

PMID- 24298384
TI  - The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural
      Damage in Rat Offspring's Hippocampus.
AB  - OBJECTIVE(S): The aim of this study was to investigate ascorbic acid and garlic
      protective effects on lead-induced neurotoxicity during rat hippocampus
      development. MATERIALS AND METHODS: 90 pregnant wistar rats were divided randomly
      into nine groups: 1- Animals received leaded water (L). 2- Rats received leaded
      water and ascorbic acid (L+AA). 3- Animals received leaded water and garlic juice
      (L+G). 4-Animals received leaded water, ascorbic acid and garlic juice (L+G+AA).
      5- Rats treated with ascorbic acid (AA). 6- Rats treated with garlic juice (G). 7
      Rats treated with ascorbic acid and garlic juice (AA+G). 8- Rats treated with
      tap water plus 0.4 ml/l normal hydrogen chloride (HCl) and 0.5 mg/l Glucose
      (Sham). 9- Normal group (N). Leaded water (1500 ppm), garlic juice (1
      ml/100g/day, gavage) and ascorbic acid (500 mg/kg/day, IP) were used. Finally,
      blood lead levels (BLL) were measured in both rats and their offspring. The rat
      offspring brain sections were stained using Toluidine Blue and photographed. Dark
      neurons (DNs) were counted to compare all groups. RESULTS: BLL significantly
      increased in L group compared to control and sham groups and decreased in L+G and
      L+AA groups in comparison to the L group (P<0.05). the number of DNs in the CA1,
      CA3, and DG of rat offspring hippocampus significantly increased in L group in
      comparison to control and sham groups (P<0.05) and decreased in L+G and L+AA
      groups compared to L group (P<0.05). CONCLUSION: Garlic juice and ascorbic acid
      administration during pregnancy and lactation may protect lead-induced neural
      damage in rat offspring hippocampus.

PMID- 24298385
TI  - Consequences of the Combined alpha-tocopherol, Ascorbic Acid and alpha-lipoic
      Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and
      Liver of Diabetic Rats.
AB  - OBJECTIVE(S): Our objective was to evaluate the effects of a triple antioxidant
      combination [alpha-tocopherol (AT), ascorbic acid (AA) and alpha-lipoic acid
      (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid
      composition of liver and muscle tissues in diabetic rats. MATERIALS AND METHODS:
      Forty-three Wistar rats were randomly divided into five groups. The first group
      was used as a control. The second, third and fourth groups received STZ (45
      mg/kg) in citrate buffer. The fourth and fifth groups were injected with
      intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and
      received water-soluble vitamin C (50 mg/kg) in their drinking water for a period
      of six weeks. RESULTS: Liver cholesterol levels in the AT+AA+LA group were lower
      than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were
      higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P<= 0.05). The
      muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the
      control group (P<= 0.05). The levels of oleic acid were higher in the D-1 group
      and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D
      2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. CONCLUSION: Our
      results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme
      products in liver tissues of diabetic and non-diabetic rats were increased by
      triple antioxidant mixture.

PMID- 24298386
TI  - Detection of magA Gene in Klebsiella spp. Isolated from Clinical SamplesDetection
      of magA.
AB  - OBJECTIVE(S): Klebsiella infections are caused mainly by K. pneumoniae and K.
      oxytoca. In the last two decades, a new type of invasive Klebsiella pneumoniae
      which contains mucoviscosity-associated gene (magA) has emerged. The aim of this
      study was to investigate the prevalence of magA gene and to detect antimicrobial
      susceptibility patterns of Klebsiella spp. isolated from clinical samples.
      MATERIALS AND METHODS: Klebsiella isolates were collected from patients admitted
      to referral hospitals of Hamadan, Iran, during a 12-month period from 2007 to
      2008. The samples were analyzed by conventional microbiological methods and
      polymerase chain reaction (PCR). The hypermucoviscosity (HV) phenotype of
      Klebsiella isolates was characterized by formation of viscous strings >5 mm as a
      positive test. The susceptibility of isolates to routine antibiotics was assessed
      by agar disk diffusion method. RESULTS: Out of 105 Klebsiella isolates, 96.2% was
      identified as K. pneumoniae and 3.8% as K. oxytoca by PCR. magA gene was detected
      in 4 (3.8%) isolates of K. pneumoniae. The isolates of K. oxytoca contained no
      magA gene. From 4 isolates with positive magA gene, two of them were HV+ and two
      were HV- phenotype. Overall, sixty-four isolates (60.95%) of K. pneumoniae showed
      an HV positive phenotype and all isolates of K. oxytoca were HV- phenotype. The
      most effective antibiotics against the isolates were tobramycin (79.05%),
      ceftazidime (79.05%), ceftizoxime (78.09%), ciprofloxacin (76.19%), ceftriaxone
      (76.24%) and amikacin (74.29%). CONCLUSION: The results suggest that there is
      also magA associated serotype of the K. pneumoniae in this region. In addition,
      the presence of HV+ phenotype may not be associated with magA.

PMID- 24298387
TI  - The role of target and bystander cells in dose-response relationship of radiation
      induced bystander effects in two cell lines.
AB  - OBJECTIVE(S): Radiation effect induced in nonirradiated cells which are adjacent
      or far from irradiated cells is termed radiation-induced bystander effect (RIBE).
      Published data on dose-response relationship of RIBE is controversial. In the
      present study the role of targeted and bystander cells in RIBE dose-response
      relationship of two cell lines have been investigated. MATERIALS AND METHODS: Two
      cell lines (QU-DB and MRC5) which had previously exhibited different dose
      response relationship were selected. In the previous study the two cell lines
      received medium from autologous irradiated cells and the results showed that the
      magnitude of damages induced in QU-DB cells was dependent on dose unlike MRC5
      cells. In the present study, the same cells irradiated with 0.5, 2 and 4 Gy gamma
      rays and their conditioned media were transferred to nonautologous bystander
      cells; such that the bystander effects due to cross-interaction between them were
      studied. Micronucleus assay was performed to measure the magnitude of damages
      induced in bystander cells (RIBE level). RESULTS: QU-DB cells exhibited a dose
      dependent response. RIBE level in MRC5 cells which received medium from 0.5 and 2
      Gy QU-DB irradiated cells was not statistically different, but surprisingly when
      they received medium from 4Gy irradiated QU-DB cells, RIBE was abrogated.
      CONCLUSION: RESULTS pertaining to QU-DB and MRC5 cells indicated that both target
      and bystander cells determined the outcome. Triggering the bystander effect
      depended on the radiation dose and the target cell-type, but when RIBE was
      triggered, dose-response relationship was predominantly determined by the
      bystander cell type.

PMID- 24298388
TI  - Anal involvement in pemphigus vularis.
AB  - Background. Pemphigus vulgaris (PV) is an autoimmune blistering disease of the
      skin and mucosa. Anal mucosa may be involved in PV, but the frequency and
      clinical profile are not fully ascertained. Objective. The aim was to investigate
      the involvement of the anal area in newly diagnosed PV patients. Patients and
      Methods. A total of 168 consecutive newly diagnosed PV patients were enrolled.
      Anal symptoms and signs, involvement of other body sites, and severity of disease
      were recorded. Results. A total of 47 out of 168 patients (27.9%) had involvement
      of the anal area. Anal involvement was significantly associated with PV lesions
      in ophthalmic (P = 0.03), nasal (P = 0.02), and genital mucosa (P < 0.001) but
      not the oral cavity (P = 0.24). There was a significant association between
      number of involved mucosal sites and anal involvement (P < 0.001). Anal
      involvement was associated with oral severity (P = 0.02). Constipation was the
      most frequent symptom (73.8%) followed by pain on defecation (50%). Seventeen
      patients (36%) were symptom-free. Erosion was the most frequent sign (91.5%).
      Conclusion. Anal involvement in PV seems to be more frequent than previously
      assumed. Routine anal examination is recommended even in asymptomatic patients as
      anal involvement appears to correlate with the severity of PV. 

PMID- 24298389
TI  - Assessment of Factors Associated with Breast Self-Examination among Health
      Extension Workers in West Gojjam Zone, Northwest Ethiopia.
AB  - Background. Early detection of breast cancer using breast self-examination (BSE)
      plays an important role in decreasing its morbidity and mortality. Objective. To
      identify factors associated with BSE among health extension workers in Northwest
      Ethiopia. Methods. Cross-sectional study design was employed from October to
      November, 2012 in West Gojjam Zone of Amhara region. Simple random sampling
      technique was used to recruit a total of 390 health extension workers (HEWs). A
      structured Amharic questionnaire was used to collect the data. Data were entered
      and analyzed using SPSS statistical package version 16.0. Result. This study
      found that 37% of HEWs had ever practiced BSE and 14.4% practiced it regularly.
      The three main reasons for not doing regular BSE were no breast problem (53.2%),
      not knowing the technique of BSE (30.6%), and not knowing the importance of BSE
      (21.4%). Discussion with families on BSE and history of breast examination by
      health professionals were found significantly associated with ever practice of
      BSE. Conclusion. BSE practice was found low in this study. Having information on
      the importance of BSE was predictor of BSE practice. Therefore, it is important
      to give training on BSE techniques and its role on breast cancer prevention for
      HEWs. 

PMID- 24298390
TI  - Assessment of regulatory T cells in childhood immune thrombocytopenic purpura.
AB  - This study had the objective to assess the frequency of Tregs in children newly
      diagnosed with ITP and ascertain whether an association exists between Tregs and
      platelet counts, by means of a comparison with healthy controls. This case
      control study included 19 patients newly diagnosed with ITP-whose blood samples
      were collected at four points in time: before any therapy and 1, 3, and 6 months
      after diagnosis-and 19 healthy controls. Tregs (CD4(+) CD25(+)Foxp3 T cells) were
      evaluated by flow cytometry. There was a statistically significant difference in
      platelet count between the case and control groups. There were no significant
      differences in Treg counts between cases and controls at any point during the
      course of the study and no difference in Treg counts between the chronic and
      nonchronic groups and no significant correlation between Tregs and platelet
      counts in the case and control groups. The findings of this study did not show
      any statistically significant correlation between Tregs and number of platelets
      in the case and control groups. Treg cells did not play a role in the regulation
      of autoimmunity in children with ITP. 

PMID- 24298391
TI  - Chromosome aberrations in cells infected with bovine papillomavirus: comparing
      cutaneous papilloma, esophagus papilloma, and urinary bladder lesion cells.
AB  - THE MAJORITY OF MALIGNANT CELLS PRESENT GENETIC INSTABILITY WITH CHROMOSOME
      NUMBER CHANGES PLUS SEGMENTAL DEFECTS: these changes involve intact chromosomes
      and breakage-induced alterations. Some pathways of chromosomal instability have
      been proposed as random breakage, telomere fusion, and centromere fission.
      Chromosome alterations in tumor cells have been described in animal models and in
      vitro experiments. One important question is about possible discrepancies between
      animal models, in vitro studies, and the real events in cancer cells in vivo.
      Papillomaviruses are relevant agents in oncogenic processes related to action on
      host genome. Recently, many reports have discussed the presence of virus DNA in
      peripheral blood, in humans and in animals infected by papillomaviruses. The
      meaning of this event is of controversy: possible product of apoptosis occurring
      in cancer cells, metastasized cancer cells, or active DNA sequences circulating
      in bloodstream. This study compares chromosome aberrations detected in bovine
      cells, in peripheral blood cells, and in BPV lesion cells: the literature is poor
      in this type of study. Comparing chromosome aberrations described in the
      different cells, a common mechanism in their origin, can be suggested.
      Furthermore blood cells can be evaluated as an effective way of virus
      transmission. 

PMID- 24298392
TI  - Prostaglandin E 2 Does Not Modulate CCR7 Expression and Functionality after
      Differentiation of Blood Monocytes into Macrophages.
AB  - Previously, we demonstrated that prostaglandin E2 (PGE2) induces C-C chemokine
      receptor type 7 (CCR7) expression on human monocytes, which stimulates their
      subsequent migration in response to the CCR7 natural ligands CCL19 and CCL21. In
      this study, we determined whether PGE2 affects CCR7 expression on macrophages.
      Flow cytometric analysis and chemotaxis assays were performed on Mono Mac-1
      derived macrophage (MDMM-1) as well as unpolarized monocyte-derived macrophages
      (MDMs) to determine the CCR7 expression and functionality in the presence of
      PGE2. Data revealed that a MDMM-1 exhibited markedly downregulated CCR7
      expression and functionality that were partially restored by treatment with PGE2.
      In MDMs, we observed a drastic downregulation of CCR7 expression and
      functionality that were unaffected following PGE2 treatment. Our data indicate
      that monocyte differentiation induces the loss of CCR7 expression and that PGE2
      is unable to modulate CCR7 expression and functionality as shown previously in
      monocytes. 

PMID- 24298393
TI  - Automatic Spot Identification for High Throughput Microarray Analysis.
AB  - High throughput microarray analysis has great potential in scientific research,
      disease diagnosis, and drug discovery. A major hurdle toward high throughput
      microarray analysis is the time and effort needed to accurately locate gene spots
      in microarray images. An automatic microarray image processor will allow accurate
      and efficient determination of spot locations and sizes so that gene expression
      information can be reliably extracted in a high throughput manner. Current
      microarray image processing tools require intensive manual operations in addition
      to the input of grid parameters to correctly and accurately identify gene spots.
      This work developed a method, herein called auto-spot, to automate the spot
      identification process. Through a series of correlation and convolution
      operations, as well as pixel manipulations, this method makes spot identification
      an automatic and accurate process. Testing with real microarray images has
      demonstrated that this method is capable of automatically extracting subgrids
      from microarray images and determining spot locations and sizes within each
      subgrid, regardless of variations in array patterns and background noises. With
      this method, we are one step closer to the goal of high throughput microarray
      analysis.

PMID- 24298394
TI  - Feasibility study of brain tumor delineation using immunolabeled gold nanorods.
AB  - Effective treatment of patients with malignant brain tumors requires surgical
      resection of a high percentage of the bulk tumor. Surgeons require a method that
      enables delineation of tumor margins, which are not visually distinct by eye. In
      this study, the feasibility of using gold nanorods (GNRs) for this purpose is
      evaluated. Anti-Epidermal Growth Factor Receptor (anti-EGFR) conjugated GNRs are
      used to label human xenograft glioblastoma multiforme (GBM) tumors embedded
      within slices of brain tissues from healthy nude mice. The anti-EGFR GNRs exhibit
      enhanced absorption at red to near-infrared wavelengths, often referred to as the
      tissue optical window, where absorption from blood is minimal. To enable
      definition of molecular specificity and spatial accuracy of the label, the GNR
      absorption is compared with GFP fluorescence which is expressed by the GBM cells
      used here. This work demonstrates a simple but highly translational technique to
      classify normal and malignant brain tissue regions in open surgery applications
      using immunolabeled GNR contrast agents. 

PMID- 24298395
TI  - Henle fiber layer phase retardation measured with polarization-sensitive optical
      coherence tomography.
AB  - We developed a method based on polarization-sensitive optical coherence
      tomography (PS-OCT) to quantify the double pass phase retardation (DPPR) induced
      by Henle fiber layer in three subjects. Measurements of the retina were performed
      at a mean wavelength of 840 nm using two polarization states that were
      perpendicular in a Poincare sphere representation and phase retardation
      contributions from tissue layers above and below the Henle fiber layer were
      excluded using appropriately placed reference and measurement points. These
      points were semi-automatically segmented from intensity data. Using a new
      algorithm to determine DPPR, the Henle fiber layer in three healthy subjects aged
      50-60 years showed elevated DPPR in a concentric ring about the fovea, with an
      average maximum DPPR for the three subjects of 22.0 degrees  (range: 20.4 degrees
      to 23.0 degrees ) occurring at an average retinal eccentricity of 1.8 degrees 
      (range: 1.5 degrees  to 2.25 degrees ). Outside the ring, a floor of
      approximately 6.8 degrees  was measured, which we show can mainly be attributed
      to phase noise that is induced in the polarization states. We also demonstrate
      the method can determine fast axis orientation of the retardation, which is found
      consistent with the known radial pattern of Henle fibers. 

PMID- 24298396
TI  - Handheld simultaneous scanning laser ophthalmoscopy and optical coherence
      tomography system.
AB  - Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) are
      widely used retinal imaging modalities that can assist in the diagnosis of
      retinal pathologies. The combination of SLO and OCT provides a more comprehensive
      imaging system and a method to register OCT images to produce motion corrected
      retinal volumes. While high quality, bench-top SLO-OCT systems have been
      discussed in the literature and are available commercially, there are currently
      no handheld designs. We describe the first design and fabrication of a handheld
      SLO/spectral domain OCT probe. SLO and OCT images were acquired simultaneously
      with a combined power under the ANSI limit. High signal-to-noise ratio SLO and
      OCT images were acquired simultaneously from a normal subject with visible motion
      artifacts. Fully automated motion estimation methods were performed in post
      processing to correct for the inter- and intra-frame motion in SLO images and
      their concurrently acquired OCT volumes. The resulting set of reconstructed SLO
      images and the OCT volume were without visible motion artifacts. At a reduced
      field of view, the SLO resolved parafoveal cones without adaptive optics at a
      retinal eccentricity of 11 degrees  in subjects with good ocular optics. This
      system may be especially useful for imaging young children and subjects with less
      stable fixation. 

PMID- 24298397
TI  - Non-contact photoacoustic imaging using a fiber based interferometer with optical
      amplification.
AB  - In photoacoustic imaging the ultrasonic signals are usually detected by
      contacting transducers. For some applications contact with the tissue should be
      avoided. As alternatives to contacting transducers interferometric means can be
      used to acquire photoacoustic signals remotely. In this paper we report on non
      contact three and two dimensional photoacoustic imaging using an optical fiber
      based Mach-Zehnder interferometer. A detection beam is transmitted through an
      optical fiber network onto the surface of the specimen. Back reflected light is
      collected and coupled into the same optical fiber. To achieve a high signal/noise
      ratio the reflected light is amplified by means of optical amplification with an
      erbium doped fiber amplifier before demodulation. After data acquisition the
      initial pressure distribution is reconstructed by a Fourier domain reconstruction
      algorithm. We present remote photoacoustic imaging of a tissue mimicking phantom
      and on chicken skin. 

PMID- 24298398
TI  - Optical imaging of resting-state functional connectivity in a novel arterial
      stiffness model.
AB  - This study aims to assess the impact of unilateral increases in carotid stiffness
      on cortical functional connectivity measures in the resting state. Using a novel
      animal model of induced arterial stiffness combined with optical intrinsic
      signals and laser speckle imaging, resting state functional networks derived from
      hemodynamic signals are investigated for their modulation by isolated changes in
      stiffness of the right common carotid artery. By means of seed-based analysis,
      results showed a decreasing trend of homologous correlation in the motor and
      cingulate cortices. Furthermore, a graph analysis indicated a randomization of
      the cortex functional networks, suggesting a loss of connectivity, more
      specifically in the motor cortex lateral to the treated carotid, which however
      did not translate in differentiated metabolic activity. 

PMID- 24298399
TI  - Quantitative laser speckle flowmetry of the in vivo microcirculation using
      sidestream dark field microscopy.
AB  - We present integrated Laser Speckle Contrast Imaging (LSCI) and Sidestream Dark
      Field (SDF) flowmetry to provide real-time, non-invasive and quantitative
      measurements of speckle decorrelation times related to microcirculatory flow.
      Using a multi exposure acquisition scheme, precise speckle decorrelation times
      were obtained. Applying SDF-LSCI in vitro and in vivo allows direct comparison
      between speckle contrast decorrelation and flow velocities, while imaging the
      phantom and microcirculation architecture. This resulted in a novel analysis
      approach that distinguishes decorrelation due to flow from other additive
      decorrelation sources. 

PMID- 24298400
TI  - Monitoring of wound healing process of human skin after fractional laser
      treatments with optical coherence tomography.
AB  - Fractional photothermolysis induced by non-ablative fractional lasers (NAFLs) or
      ablative fractional lasers (AFLs) can remodel the skin, regenerate collagen, and
      remove tumor tissue. However, fractional laser treatments may result in severe
      side effects, and multiple treatments are required to achieve the expected
      outcome. Thus, the treatment outcome and downtime after fractional laser
      treatments are key issues to determine the following treatment strategy. In this
      study, an optical coherence tomography (OCT) system was implemented for in vivo
      studies of wound healing after NAFL and AFL treatments. According to the OCT
      scanning results, the laser-induced photothermolysis including volatilization and
      coagulation could be morphologically identified. To continue monitoring the wound
      healing process, the treated regions were scanned with OCT at different time
      points, and the en-face images at various tissue depths were extracted from three
      dimensional OCT images. Furthermore, to quantitatively evaluate the morphological
      changes at different tissue depths during wound healing, an algorithm was
      developed to distinguish the backscattering properties of untreated and treated
      tissues. The results showed that the coagulation damage induced by the NAFLs
      could be rapidly healed in 6 days. In contrast, the tissue volatilization induced
      by AFLs required a longer recovery time of 14 days. In conclusion, this study
      establishes the feasibility of this methodology as a means of clinically
      monitoring treatment outcomes and wound healing after fractional laser
      treatments. 

PMID- 24298401
TI  - High-speed hyperspectral Raman imaging for label-free compositional
      microanalysis.
AB  - We present high-speed hyperspectral Raman imaging with integrated active
      illumination for label-free compositional microanalysis. We show that high
      quality Raman spectra can be acquired from as many as ~1,000 spots/sec semi
      randomly distributed among a ~100x100 MUm(2) area without mechanical scanning. We
      demonstrate rapid data acquisition from three types of samples: 1) uniform,
      strong Raman scatterers, e.g., silicon substrates; 2) non-uniform, medium
      strength Raman scatterers, e.g., polymer microparticles; and, 3) non-uniform,
      relatively weak Raman scatterers, e.g., bacterial spores. We compare the system
      performance to that of point-scan with an electron-multiplied CCD camera, as
      implemented in some commercial systems. The results suggest that our system not
      only provides significant imaging speed advantage for various types of samples,
      but also permits substantially longer integration time per spot, leading to
      superior signal-to-noise ratio data. Our system enables the rapid collection of
      high quality Raman spectra for reliable and robust compositional microanalysis
      that are potentially transformative in applications such as semiconductor
      material and device, polymer blend and biomedicine. 

PMID- 24298402
TI  - Automated quantification of lung structures from optical coherence tomography
      images.
AB  - Characterization of the size of lung structures can aid in the assessment of a
      range of respiratory diseases. In this paper, we present a fully automated
      segmentation and quantification algorithm for the delineation of large numbers of
      lung structures in optical coherence tomography images, and the characterization
      of their size using the stereological measure of median chord length. We
      demonstrate this algorithm on scans acquired with OCT needle probes in fresh, ex
      vivo tissues from two healthy animal models: pig and rat. Automatically computed
      estimates of lung structure size were validated against manual measures. In
      addition, we present 3D visualizations of the lung structures using the
      segmentation calculated for each data set. This method has the potential to
      provide an in vivo indicator of structural remodeling caused by a range of
      respiratory diseases, including chronic obstructive pulmonary disease and
      pulmonary fibrosis. 

PMID- 24298403
TI  - Enhancement of lateral resolution and optical sectioning capability of two-photon
      fluorescence microscopy by combining temporal-focusing with structured
      illumination.
AB  - We demonstrate super-resolution imaging with background fluorescence rejection by
      interferometric temporal focusing microscopy, in which temporal focusing is
      combined with structured illumination. The lateral resolution and the optical
      sectioning capability are simultaneously improved by factors of 1.6 and 1.4,
      respectively, compared to conventional temporal focusing microscopy. Fluorescent
      beads (200 nm diameter) that are difficult to distinguish from the background
      fluorescence in conventional temporal focusing microscopy, are clearly visualized
      by interferometric temporal focusing microscopy. 

PMID- 24298404
TI  - Extended hierarchical Bayesian diffuse optical tomography for removing scalp
      artifact.
AB  - Functional near-infrared spectroscopy (fNIRS) can non-invasively measure
      hemodynamic responses in the cerebral cortex with a portable apparatus. However,
      the observation signal in fNIRS measurements is contaminated by the artifact
      signal from the hemodynamic response in the scalp. In this paper, we propose a
      method to separate the signals from the cortex and the scalp by estimating both
      hemodynamic changes by diffuse optical tomography (DOT). In the inverse problem
      of DOT, we introduce smooth regularization to the hemodynamic change in the scalp
      and sparse regularization to that in the cortex based on the nature of the
      hemodynamic responses. These appropriate regularization models, with the spatial
      information of optical paths of many measurement channels, allow three
      dimensional reconstruction of both hemodynamic changes. We validate our proposed
      method through two-layer phantom experiments and MRI-based head-model
      simulations. In both experiments, the proposed method simultaneously estimates
      the superficial smooth activity in the scalp area and the deep localized activity
      in the cortical area. 

PMID- 24298405
TI  - Narrow band 3 * 3 Mueller polarimetric endoscopy.
AB  - Mueller matrix polarimetric imaging has shown potential in tissue diagnosis but
      is challenging to implement endoscopically. In this work, a narrow band 3 * 3
      Mueller matrix polarimetric endoscope was designed by rotating the endoscope to
      generate 0 degrees , 45 degrees  and 90 degrees  linearly polarized illumination
      and positioning a rotating filter wheel in front of the camera containing three
      polarisers to permit polarization state analysis for backscattered light. The
      system was validated with a rotating linear polarizer and a diffuse reflection
      target. Initial measurements of 3 * 3 Mueller matrices on a rat are demonstrated,
      followed by matrix decomposition into the depolarization and retardance matrices
      for further analysis. Our work shows the feasibility of implementing polarimetric
      imaging in a rigid endoscope conveniently and economically in order to reveal
      diagnostic information. 

PMID- 24298406
TI  - Computational analysis of endometrial photocoagulation with diffusing optical
      device.
AB  - A balloon-catheter optical diffuser for endometrial treatment was evaluated with
      computational thermal analysis. Various catheter materials and dimensions were
      implemented to identify the optimal design for the device. Spatial and temporal
      development of temperature during 30-sec irradiation of 532-nm light demonstrated
      thermal insulation effects of polyurethane on temperature increase up to 384 K,
      facilitating the irreversible denaturation. The current model revealed the degree
      of thermal coagulation 13% thicker than experimental results possibly due to lack
      of tissue dynamics and light intensity distribution. In combination with photon
      distribution, the analytical simulation can be a feasible tool to optimize the
      new optical diffuser for efficient and safe endometrial treatment. 

PMID- 24298407
TI  - Photoacoustic measurement of refractive index of dye solutions and myoglobin for
      biosensing applications.
AB  - Current methods of determining the refractive index of chemicals and materials,
      such as ellipsometry and reflectometry, are limited by their inability to analyze
      highly absorbing or highly transparent materials, as well as the required prior
      knowledge of the sample thickness and estimated refractive index. Here, we
      present a method of determining the refractive index of solutions using the
      photoacoustic effect. We show that a photoacoustic refractometer can analyze
      highly absorbing dye samples to within 0.006 refractive index units of a handheld
      optical refractometer. Further, we use myoglobin, an early non-invasive biomarker
      for malignant hyperthermia, as a proof of concept that this technique is
      applicable for use as a medical diagnostic. Comparison of the speed, cost,
      simplicity, and accuracy of the techniques shows that this photoacoustic method
      is well-suited for optically complex systems. 

PMID- 24298408
TI  - In vitro characterization of genetically expressed absorbing proteins using
      photoacoustic spectroscopy.
AB  - Genetically expressed fluorescent proteins have been shown to provide
      photoacoustic contrast. However, they can be limited by low photoacoustic
      generation efficiency and low optical absorption at red and near infrared
      wavelengths, thus limiting their usefulness in mammalian small animal models. In
      addition, many fluorescent proteins exhibit low photostability due to
      photobleaching and transient absorption effects. In this study, we explore these
      issues by synthesizing and characterizing a range of commonly used fluorescent
      proteins (dsRed, mCherry, mNeptune, mRaspberry, AQ143, E2 Crimson) and novel non
      fluorescent chromoproteins (aeCP597 and cjBlue and a non-fluorescent mutant of E2
      Crimson). The photoacoustic spectra, photoacoustic generation efficiency and
      photostability of each fluorescent protein and chromoprotein were measured.
      Compared to the fluorescent proteins, the chromoproteins were found to exhibit
      higher photoacoustic generation efficiency due to the absence of radiative
      relaxation and ground state depopulation, and significantly higher
      photostability. The feasibility of converting an existing fluorescent protein
      into a non-fluorescent chromoprotein via mutagenesis was also demonstrated. The
      chromoprotein mutant exhibited greater photoacoustic signal generation efficiency
      and better agreement between the photoacoustic and the specific extinction
      coefficient spectra than the original fluorescent protein. Lastly, the genetic
      expression of a chromoprotein in mammalian cells was demonstrated. This study
      suggests that chromoproteins may have potential for providing genetically encoded
      photoacoustic contrast. 

PMID- 24298409
TI  - Four-dimensional visualization of subpleural alveolar dynamics in vivo during
      uninterrupted mechanical ventilation of living swine.
AB  - Pulmonary alveoli have been studied for many years, yet no unifying hypothesis
      exists for their dynamic mechanics during respiration due to their miniature size
      (100-300 MUm dimater in humans) and constant motion, which prevent standard
      imaging techniques from visualizing four-dimensional dynamics of individual
      alveoli in vivo. Here we report a new platform to image the first layer of air
      filled subpleural alveoli through the use of a lightweight optical frequency
      domain imaging (OFDI) probe that can be placed upon the pleura to move with the
      lung over the complete range of respiratory motion. This device enables in-vivo
      acquisition of four-dimensional microscopic images of alveolar airspaces (alveoli
      and ducts), within the same field of view, during continuous ventilation without
      restricting the motion or modifying the structure of the alveoli. Results from an
      exploratory study including three live swine suggest that subpleural alveolar air
      spaces are best fit with a uniform expansion (r (2) = 0.98) over a recruitment
      model (r (2) = 0.72). Simultaneously, however, the percentage change in volume
      shows heterogeneous alveolar expansion within just a 1 mm x 1 mm field of view.
      These results signify the importance of four-dimensional imaging tools, such as
      the device presented here. Quantification of the dynamic response of the lung
      during ventilation may help create more accurate modeling techniques and move
      toward a more complete understanding of alveolar mechanics. 

PMID- 24298410
TI  - Introduction to the BODA 2013 feature issue.
AB  - The guest editors introduce a feature issue containing papers based on research
      presented at the BODA 2013 meeting. 

PMID- 24298411
TI  - Improved visualization of outer retinal morphology with aberration cancelling
      reflective optical design for adaptive optics - optical coherence tomography.
AB  - We present an aberration cancelling optical design for a reflective adaptive
      optics - optical coherence tomography (AO-OCT) retinal imaging system. The
      optical performance of this instrument is compared to our previous multimodal AO
      OCT/AO-SLO retinal imaging system. The feasibility of new instrumentation for
      improved visualization of microscopic retinal structures is discussed. Examples
      of images acquired with this new AO-OCT instrument are presented. 

PMID- 24298412
TI  - Signal and depth enhancement for in vivo flow cytometer measurement of ear skin
      by optical clearing agents.
AB  - The in vivo flow cytometry (IVFC) has shown a great potential for detecting
      circulating tumor cells quantitatively in the bloodstream. However, the detection
      depth suffers from the strong light scattering of tissue. In this study, an
      innovative ear skin optical clearing agent (ESOCA) is employed to improve the
      signal quality of the IVFC. Our results show that compared with commonly used
      glycerol, topical application of ESOCA can enhance the transmittance of rat ear
      significantly in vivo. The labeled red blood cells can be detected by the IVFC
      with higher signal quality and greater detection depth. This study is very
      helpful for potential tumor metastasis studies by the IVFC in deep tissues. 

PMID- 24298413
TI  - In vivo imaging of retinal pigment epithelium cells in age related macular
      degeneration.
AB  - Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in
      the living human eye non-invasively by imaging the short-wavelength
      autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based
      on the assumption that all subjects have the same longitudinal chromatic
      aberration (LCA) correction, has proved difficult to use in diseased eyes, and in
      particular those affected by age-related macular degeneration (AMD). In this
      work, we improve Morgan's method by accounting for chromatic aberration
      variations by optimizing the confocal aperture axial and transverse placement
      through an automated iterative maximization of image intensity. The increase in
      image intensity after algorithmic aperture placement varied depending upon
      patient and aperture position prior to optimization but increases as large as a
      factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in
      diameter, images were obtained using retinal radiant exposures of less than 2.44
      J/cm(2), which is ~22 times below the current ANSI maximum permissible exposure.
      RPE cell morphologies that were strikingly similar to those seen in postmortem
      histological studies were observed in AMD eyes, even in areas where the pattern
      of fluorescence appeared normal in commercial fundus autofluorescence (FAF)
      images. This new method can be used to study RPE morphology in AMD and other
      diseases, providing a powerful tool for understanding disease pathogenesis and
      progression, and offering a new means to assess the efficacy of treatments
      designed to restore RPE health. 

PMID- 24298414
TI  - Optical tractography of the mouse heart using polarization-sensitive optical
      coherence tomography.
AB  - We developed a method to image myocardial fiber architecture in the mouse heart
      using a Jones matrix-based polarization-sensitive optical coherence tomography
      (PSOCT) system. The "cross-helical" laminar structure of myocardial fibers can be
      clearly visualized using this technology. The obtained myocardial fiber
      organization agrees well with existing knowledge acquired using conventional
      histology and diffusion tensor magnetic resonance imaging. 

PMID- 24298415
TI  - Application of quantitative second-harmonic generation microscopy to dynamic
      conditions.
AB  - We present a quantitative second-harmonic generation (SHG) imaging technique that
      quantifies the 2D spatial organization of collagen fiber samples under dynamic
      conditions, as an image is acquired. The technique is demonstrated for both a
      well-aligned tendon sample and a randomly aligned, sparsely distributed collagen
      scaffold sample. For a fixed signal-to-noise ratio, we confirm the applicability
      of this method for various window sizes (pixel areas) as well as with using a
      gridded overlay map that allows for correlations of fiber orientations within a
      given image. This work has direct impact to in vivo biological studies by
      incorporating simultaneous SHG image acquisition and analysis. 

PMID- 24298416
TI  - Design and evaluation of a laboratory prototype system for 3D photoacoustic full
      breast tomography.
AB  - Photoacoustic imaging can visualize vascularization-driven optical absorption
      contrast with great potential for breast cancer detection and diagnosis. State-of
      the-art photoacoustic breast imaging systems are promising but are limited either
      by only a 2D imaging capability or by an insufficient imaging field-of-view
      (FOV). We present a laboratory prototype system designed for 3D photoacoustic
      full breast tomography, and comprehensively characterize it and evaluate its
      performance in imaging phantoms. The heart of the system is an ultrasound
      detector array specifically developed for breast imaging and optimized for high
      sensitivity. Each detector element has an acoustic lens to enlarge the acceptance
      angle of the large surface area detector elements to ensure a wide system FOV. We
      characterized the ultrasound detector array performance in terms of frequency
      response, directional sensitivity, minimum detectable pressure and inter-element
      electrical and mechanical cross-talk. Further we evaluated the system performance
      of the laboratory prototype imager using well-defined breast mimicking phantoms.
      The system possesses a 2 mm XY plane resolution and a 6 mm vertical resolution. A
      vasculature mimicking object was successfully visualized down to a depth of 40 mm
      in the breast phantom. Further, tumor mimicking spherical objects with 5 and 10
      mm diameter at 20 mm and 40 mm depths are recovered, indicating high system
      sensitivity. The system has a 170 * 170 * 170 mm(3) FOV, which is well suited for
      full breast imaging. Various recommendations are provided for performance
      improvement and to guide this laboratory prototype to a clinical version in
      future. 

PMID- 24298417
TI  - Quantitative comparison of analysis methods for spectroscopic optical coherence
      tomography.
AB  - Spectroscopic optical coherence tomography (sOCT) enables the mapping of
      chromophore concentrations and image contrast enhancement in tissue. Acquisition
      of depth resolved spectra by sOCT requires analysis methods with optimal
      spectral/spatial resolution and spectral recovery. In this article, we
      quantitatively compare the available methods, i.e. the short time Fourier
      transform (STFT), wavelet transforms, the Wigner-Ville distribution and the dual
      window method through simulations in tissue-like media. We conclude that all
      methods suffer from the trade-off in spectral/spatial resolution, and that the
      STFT is the optimal method for the specific application of the localized
      quantification of hemoglobin concentration and oxygen saturation. 

PMID- 24298418
TI  - Automated lamina cribrosa microstructural segmentation in optical coherence
      tomography scans of healthy and glaucomatous eyes.
AB  - We demonstrate an automated segmentation method for in-vivo 3D optical coherence
      tomography (OCT) imaging of the lamina cribrosa (LC). Manual segmentations of
      coronal slices of the LC were used as a gold standard in parameter selection and
      evaluation of the automated technique. The method was validated using two
      prototype OCT devices; each had a subject cohort including both healthy and
      glaucomatous eyes. Automated segmentation of in-vivo 3D LC OCT microstructure
      performed comparably to manual segmentation and is useful for investigative
      research and in clinical quantification of the LC. 

PMID- 24298420
TI  - Epidural catheter with integrated light guides for spectroscopic tissue
      characterization.
AB  - Epidural catheters are used to deliver anesthetics and opioids for managing pain
      in many clinical scenarios. Currently, epidural catheter insertion is performed
      without information about the tissues that are directly ahead of the catheter. As
      a result, the catheter can be incorrectly positioned within a blood vessel, which
      can cause toxicity. Recent studies have shown that optical reflectance
      spectroscopy could be beneficial for guiding needles that are used to insert
      catheters. In this study, we investigate the whether this technique could benefit
      the placement of catheters within the epidural space. We present a novel optical
      epidural catheter with integrated polymer light guides that allows for optical
      spectra to be acquired from tissues at the distal tip. To obtain an initial
      indication of the information that could be obtained, reflectance values and
      photon penetration depth were estimated using Monte Carlo simulations, and
      optical reflectance spectra were acquired during a laminectomy of a swine ex
      vivo. Large differences between the spectra acquired from epidural adipose tissue
      and from venous blood were observed. The optical catheter has the potential to
      provide real-time detection of intravascular catheter placement that could reduce
      the risk of complications. 

PMID- 24298419
TI  - Development and optimization of near-IR contrast agents for immune cell tracking.
AB  - Gold nanorods (NRs) are attractive for in vivo imaging due to their high optical
      cross-sections and tunable absorbance. However, the feasibility of using NRs for
      cell tracking has not been fully explored. Here, we synthesized dye doped silica
      coated NRs as multimodal contrast agents for imaging of macrophages - immune
      cells which play an important role in cancer and cardiovascular diseases. We
      showed the importance of silica coating in imaging of NR-labeled cells.
      Photoacoustic (PA) imaging of NRs labeled macrophages showed high sensitivity.
      Therefore, these results provide foundation for applications of silica-coated NRs
      and PA imaging in tracking of immune cells. 

PMID- 24298421
TI  - Combining independent component analysis and Granger causality to investigate
      brain network dynamics with fNIRS measurements.
AB  - In this study a new strategy that combines Granger causality mapping (GCM) and
      independent component analysis (ICA) is proposed to reveal complex neural network
      dynamics underlying cognitive processes using functional near infrared
      spectroscopy (fNIRS) measurements. The GCM-ICA algorithm implements the following
      two procedures: (i) extraction of the region of interests (ROIs) of cortical
      activations by ICA, and (ii) estimation of the direct causal influences in local
      brain networks using Granger causality among voxels of ROIs. Our results show
      that the use of GCM in conjunction with ICA is able to effectively identify the
      directional brain network dynamics in time-frequency domain based on fNIRS
      recordings. 

PMID- 24298422
TI  - Re-scan confocal microscopy: scanning twice for better resolution.
AB  - We present a new super-resolution technique, Re-scan Confocal Microscopy (RCM),
      based on standard confocal microscopy extended with an optical (re-scanning) unit
      that projects the image directly on a CCD-camera. This new microscope has
      improved lateral resolution and strongly improved sensitivity while maintaining
      the sectioning capability of a standard confocal microscope. This simple
      technology is typically useful for biological applications where the combination
      high-resolution and high-sensitivity is required. 

PMID- 24298423
TI  - Photoacoustic microscopy: a potential new tool for evaluation of angiogenesis
      inhibitor.
AB  - The feasibility of photoacoustic microscopy (PAM) for evaluation of angiogenesis
      inhibitor was investigated on a chick embryo model in vivo. Different
      concentrations of the angiogenesis inhibitor, Sunitinib, were applied to the
      chorioallantoic membrane (CAM) of the chick embryos. Imaging of microvasculature
      in embryo CAMs was acquired using a laser-scanning PAM system; while the optical
      microscopy (OM) capturing the microvascular images of the same set of CAMs for
      comparison served as a gold standard for validating the results from PAM. The
      microvascular density as a function of applied Sunitinib concentration has been
      quantified in both PAM and OM images. The results from these two modalities have
      a good agreement, suggesting that PAM could provide an unbiased quantification of
      microvascular density for objective evaluation of anti-angiogenesis medication.
      In comparison with conventional OM which enables only two-dimensional enface
      imaging, PAM is capable of three-dimensional analysis of microvessels, including
      not only morphology but also functions, as demonstrated in part by the imaging
      result on a canine bladder model. The emerging PAM technique shows promise to be
      used in clinical and preclinical settings for comprehensive and objective
      evaluation of anti-angiogenesis medications. 

PMID- 24298424
TI  - Accelerated rescaling of single Monte Carlo simulation runs with the Graphics
      Processing Unit (GPU).
AB  - To interpret fiber-based and camera-based measurements of remitted light from
      biological tissues, researchers typically use analytical models, such as the
      diffusion approximation to light transport theory, or stochastic models, such as
      Monte Carlo modeling. To achieve rapid (ideally real-time) measurement of tissue
      optical properties, especially in clinical situations, there is a critical need
      to accelerate Monte Carlo simulation runs. In this manuscript, we report on our
      approach using the Graphics Processing Unit (GPU) to accelerate rescaling of
      single Monte Carlo runs to calculate rapidly diffuse reflectance values for
      different sets of tissue optical properties. We selected MATLAB to enable non
      specialists in C and CUDA-based programming to use the generated open-source
      code. We developed a software package with four abstraction layers. To calculate
      a set of diffuse reflectance values from a simulated tissue with homogeneous
      optical properties, our rescaling GPU-based approach achieves a reduction in
      computation time of several orders of magnitude as compared to other GPU-based
      approaches. Specifically, our GPU-based approach generated a diffuse reflectance
      value in 0.08ms. The transfer time from CPU to GPU memory currently is a limiting
      factor with GPU-based calculations. However, for calculation of multiple diffuse
      reflectance values, our GPU-based approach still can lead to processing that is
      ~3400 times faster than other GPU-based approaches. 

PMID- 24298425
TI  - A simple and rapid detection of tissue adhesive-induced biochemical changes in
      cells and DNA using Raman spectroscopy.
AB  - We demonstrate a cytotoxicity evaluation of tissue adhesive using Raman
      spectroscopy. This method allows for quantitative, label-free, non-invasive and
      rapid monitoring of the biochemical changes of cells following tissue adhesive
      treatment. Here, we show the biochemical property changes in mouse fibroblast
      L929 cells and cellular DNA following tissue adhesive (Dermabond) treatment using
      Raman spectroscopy. The Raman band intensities were significantly decreased when
      the cells were treated with Dermabond as compared to control cells. These results
      suggest denaturation and conformational changes in proteins and degradation of
      DNA related to cell death. To support these conclusions, conventional
      cytotoxicity assays such as WST, LIVE/DEAD, and TUNEL were carried out, and the
      results were in agreement with the Raman results. Thus, Raman spectroscopy
      analysis not only distinguishes between viable and damaged cells, but can also be
      used for identification and quantification of a cytotoxicity of tissue adhesive,
      which based on the cellular biochemical and structural changes at a molecular
      level. Therefore, we suggest that this method could be used for cytotoxic
      evaluation of tissue adhesives by rapid and sensitive detection of cellular
      changes. 

PMID- 24298426
TI  - Multimodal instrument for high-sensitivity autofluorescence and spectral optical
      coherence tomography of the human eye fundus.
AB  - In this paper we present a multimodal device for imaging fundus of human eye in
      vivo which combines functionality of autofluorescence by confocal SLO with
      Fourier domain OCT. Native fluorescence of human fundus was excited by modulated
      laser beam (lambda = 473 nm, 20 MHz) and lock-in detection was applied resulting
      in improving sensitivity. The setup allows for acquisition of high resolution OCT
      and high contrast AF images using fluorescence excitation power of 50-65 MUW
      without averaging consecutive images. Successful functioning of constructed
      device have been demonstrated for 8 healthy volunteers of different age ranging
      from 24 to 83 years old. 

PMID- 24298428
TI  - Introduction: Optical trapping and applications feature issue.
AB  - The editors introduce the Biomedical Optics Express feature issue on "Optical
      Trapping and Applications." The works presented in the papers within this issue
      include were the focus of the third OTA Topical Meeting that was held on April 14
      18, 2013, in Waikoloa, Hawaii. 

PMID- 24298427
TI  - Quantitative physiology and immunohistochemistry of oral lesions.
AB  - Angiogenesis and hypoxia are reported to correlate with tumor aggressiveness. In
      this study, we investigated the potential of optically measured total hemoglobin
      concentration (THC) and blood oxygen saturation (StO2) as a quantitative measure
      of angiogenesis and hypoxia in oral lesions with an immunohistochemical
      comparison. 12 normal subjects and 40 oral patients (22 oral squamous cell
      carcinoma (SCC), 18 benign/premalignant lesions including 11 verrucous
      hyperplasia (VH) and 7 hyperkeratosis/parakeratosis (HK)) were studied. The
      results showed that the THC measurement was consistent with vascular endothelial
      growth factor (VEGF) and microvessel staining in the stromal area, but StO2 was
      not associated with HIF-1alpha. We observed inflammation induced neovascular
      formation in the stromal area of VH and HK that were likely attributed to higher
      than-control THC and StO2 and resulted in no difference in optical measurements
      between all lesions. However, we found that in majority of SCC, the ratio of THC
      and StO2 levels between lesions and the surrounding tissues provide potential
      distinguishing characteristics from VH, which are not visually differentiable
      from SCC, with a sensitivity, specificity, and accuracy of 91%, 68%, and 76%,
      respectively. 

PMID- 24298429
TI  - Psychosocial and Health Behavior Outcomes of Young Adults with Asthma or
      Diabetes.
AB  - PURPOSE: Previous research has shown a relationship between childhood/adolescent
      chronic conditions and negative health behaviors, psychological outcomes, and
      social outcomes. Less is known about whether these negative outcomes are
      experienced by young adults with chronic health conditions. The purpose of this
      paper is to investigate how young adults' BMI, health behaviors, and
      psychological and social outcomes differ depending on whether they have diabetes,
      asthma, or neither of these chronic conditions. METHODS: Data were drawn from the
      third wave of Project EAT-III: Eating and Activity in Young Adults, a population
      based study of 2287 young adults (mean age = 25.3; range 19.8 - 31.2). General
      linear models were used to test differences in BMI, health behaviors (e.g., fast
      food intake) and psychosocial outcomes (e.g. depressive symptoms) by young
      adults' chronic disease status. RESULTS: Young adults with diabetes had higher
      BMIs, engaged in less physical activity and more unhealthy weight control
      behaviors and binge eating, had lower self-esteem and lower body satisfaction,
      and experienced more depressive symptoms and appearance-based teasing compared to
      young adults with asthma or no chronic conditions, after adjusting for age,
      race/ethnicity, socio-economic status (SES) and, when relevant, for BMI. There
      were no significant differences between young adults with asthma and young adults
      with no chronic condition on all of the psychosocial and health behavior
      outcomes. CONCLUSIONS: Young adults with diabetes reported higher prevalence of
      negative health behaviors and psychosocial outcomes. Providers may find it useful
      to assess for negative health behaviors and psychosocial variables with young
      adults with diabetes in order to improve treatment and quality of life for these
      individuals.

PMID- 24298430
TI  - Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and
      Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric
      Nanoparticles.
AB  - Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in
      vivo is expected to enhance therapeutic effect with significantly less non
      specific toxicity. Active targeting is based on surface modification of
      nanoparticles with ligands that bind with extracellular targets and enhance
      payload delivery in the cells. In this study, we have used label-free Raman micro
      spectral analysis and kinetic modeling to study cellular interactions and
      intracellular delivery of C6-ceramide using a non-targeted and an epidermal
      growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery
      systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The
      results show that EGFR peptide-modified nanoparticles were rapidly internalized
      in SKOV3 cells leading to significant intracellular accumulation as compared to
      non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral
      analysis enables visualization and quantification of the carrier system, drug
      load, and responses of the biological systems interrogated, without exogenous
      staining and labeling procedures. 

PMID- 24298431
TI  - Development of a PCR based marker system for easy identification and
      classification of aerobic endospore forming bacilli.
AB  - Restriction fragment length analysis of 16S rRNA gene of 52 different aerobic
      endospore forming Bacilli (AEFB) strains with HaeIII enzyme has revealed the
      presence of a 460 bp long fragment in 50 AEFB strains. BLAST analysis revealed
      that the fragment was 463 bp long and it was located at 3' end of 16S rRNA gene.
      Further specificity of this fragment for AEFB strains was checked by PCR and in
      silico methods. In PCR based method a primer pair (463 F and 463R) specific to
      this fragment was designed and this primer pair has shown amplification of 463 bp
      fragment in AEFB strains only. In in silico methods homology of primer pair and
      presence of restriction enzyme site in 16S rRNA genes were checked in 268 species
      of AEFB. Almost all species of AEFB have shown positive results for both of the
      tests. Further multiple alignments of 463 bp sequences of different species of
      AEFB have shown that it is a good marker for identification and classification of
      AEFB. 

PMID- 24298432
TI  - Ruminal impaction due to Ficus esquiroliana Levl. in Boer goats.
AB  - Ruminal impaction is considered an important internal disease in ruminants, such
      as dairy cows, sheep, and goats. It has been reported that its occurrence is
      associated with many different causes. This study describes a novel case of
      ruminal impaction caused by a plant, Ficus esquiroliana Levl., in Boer goats.
      This case suggests that Ficus esquiroliana should be taken into consideration
      when providing food for ruminants. 

PMID- 24298433
TI  - Fulvestrant up regulates UGT1A4 and MRPs through ERalpha and c-Myb pathways: a
      possible primary drug disposition mechanism.
AB  - Fulvestrant (FaslodexTM) is a pure antiestrogen that is effective in treating
      estrogen receptor-(ER) positive breast cancer tumors that are resistant to
      selective estrogen receptor modulators such as tamoxifen. Clinical trials
      investigating the utility of adding fulvestrant to other therapeutics have not
      been shown to affect cytochrome P450-mediated metabolism. Effects on phase II
      metabolism and drug resistance have not been explored. This study demonstrates
      that fulvestrant up regulates the expression of UDP glucuronosyltransferase 1A4
      (UGT1A4) >2.5- and >3.5-fold in MCF7 and HepG2 cells, respectively. Up regulation
      occurred in a time- and concentration-dependent manner, and was inhibited by
      siRNA silencing of ERalpha. Fulvestrant also up regulates multidrug resistance
      associated proteins (MRPs). There was an up regulation of MRP2 (1.5- and 3.5
      fold), and MRP3 (5.5- and 4.5-fold) in MCF7 and HepG2 cell lines, respectively,
      and an up regulation of MRP1 (4-fold) in MCF7 cells. UGT1A4 mRNA up regulation
      was significantly correlated with UGT1A4 protein expression, anastrozole
      glucuronidation, ERalpha mRNA expression and MRP mRNA expression, but not with
      ERalpha protein expression. Genetic variants in the UGT1A4 promoter (-163A, -217G
      and -219T) reduced the basal activity of UGT1A4 by 40-60%. In silico analysis
      indicated that transcription factor c-Myb binding capacity may be affected by
      these variations. Luciferase activity assays demonstrate that silencing c-Myb
      abolished UGT1A4 up regulation by fulvestrant in promoters with the common
      genotype (-163G, -217 T and -219C) in MCF7 cells. These data indicate that
      fulvestrant can influence the disposition of other UGT1A4 substrates. These
      findings suggest a clinically significant role for UGT1A4 and MRPs in drug
      efficacy. 

PMID- 24298434
TI  - Use of UPLC-ESI-MS/MS to quantitate free amino acid concentrations in micro
      samples of mammalian milk.
AB  - Although free amino acids (FAA) account for a small fraction of total nitrogen in
      mammalian milk, they are more abundant in human milk than in most formulas, and
      may serve as a readily available source of amino acids for protein synthesis, as
      well as fulfill specific physiologic roles. We used reversed phase Ultra
      Performance Liquid Chromatography (UPLC) coupled to electrospray ionization
      tandem mass spectrometry (ESI-MS/MS) technique for FAA profiling in milks from
      three species (human, rat and cow) with a simple and rapid sample preparation.
      The derivatization procedure chosen, combined with UPLC-ESI-MS/MS allowed the
      quantitation of 21 FAA using labeled amino acids (Internal Standards) over a 10
      min run time in micro-samples of mammalian milk (50 MUL). The low limit of
      quantitation was 0.05 pmol/MUL for most FAA with good repeatability and
      reproducibility (mean CV of 5.1%). Higher levels of total FAA were found in human
      (3032 MUM) and rat milk (3460 MUM) than in bovine milk (240 MUM), with wide
      differences in the abundances of specific FAA between species. This robust
      analytical method could be applied to monitor FAA profile in human breast milk,
      and open the way to individualized adjustment of FAA content for the nutritional
      management of infants. 

PMID- 24298435
TI  - Shaking chills and high body temperature predict bacteremia especially among
      elderly patients.
AB  - PURPOSES: The difference in predictors of bacteremia between elderly and non
      elderly patients is unclear despite the aging of society. The objective was to
      determine predictors of bacteremia among elderly patients aged 80 years and older
      compared to non-elderly patients aged 18 to 79 years. METHODS: A referral
      hospital-based retrospective descriptive study from April 2012 to March 2013 in
      Okinawa, Japan. All enrolled patients were adults suspected of having bacterial
      infection who had been newly admitted into the Division of Infectious Diseases.
      HIV- infected patients were excluded. Exposures were a history of shaking chills,
      prior antibiotics use within 48 hours, vital signs, and laboratory inflammation
      markers on admission. Outcome was blood culture positivity. RESULTS: Three
      hundred and sixty-six patients were enrolled. Median age was 78.5 (interquartile
      range [IQR]: 62-88). Among patients aged 18 to 79 years, shaking chills (adjusted
      odds ratio [AOR] 2.22, 95% confidence interval [CI]: 1.09-4.51) and previous
      antibiotics use (AOR 0.08, 95% CI: 0.01-0.68) were significant. However, among
      patients aged 80 years and older, shaking chills (AOR 3.06, 95% CI: 1.30-7.19)
      and body temperature above 38.5 degrees C (AOR 2.98, 95% CI: 1.30-6.83) were
      significant. CONCLUSIONS: A history of shaking chills and vital signs indicating
      high body temperature were two findings that were useful in predicting
      bacteremia, especially in elderly patients aged 80 years and older. Further study
      is needed to assess whether the result is applicable in other regions and
      populations.

PMID- 24298436
TI  - How to Manage a Public Health Crisis and Bioterrorism in Korea.

PMID- 24298437
TI  - Investigation of Biofilm Formation and its Association with the Molecular and
      Clinical Characteristics of Methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVES: To investigate the biofilm-forming related factors against MRSA
      bloodstream isolates and evaluates their clinical features and treatment outcomes
      by biofilm production. METHODS: We collected 126 consecutive methicillin
      resistant Staphylococcus aureus (MRSA) causing blood stream infections (BSIs) at
      10 tertiary hospitals from 2007 to 2009. We investigated biofilm-forming ability
      using a microtiter plate assay, and molecular characteristics including
      multilocus sequence typing, staphylococcal cassette chromosome mec and accessory
      gene regulator types. We compared the clinical characteristics and outcomes of
      patients infected with biofilm-forming and non-biofilm-forming MRSA isolates.
      RESULTS: Of the 126 samples, 86 (68.3%), including 5 strong level (OD570 >= 1.0)
      and 81 weak level (0.2 <= OD570 < 1.0), had biofilm-forming capacity. Detection
      of fibronectinbinding protein in biofilm-forming strains was significantly higher
      than biofilm non-forming ones (p = 0.001) and three enterotoxin genes (sec-seg
      sei) islands had a high frequency regardless of biofilm production. However,
      biofilm-forming strains were more likely to be multidrug resistant (three or more
      non-beta-lactam antibiotics) than biofilm non-forming ones [79.2% vs. 59.2%, p =
      0.015, odds ratio (OR) 2.629, 95% confidence interval (CI) 1.92-5.81]. Clinical
      features of patients with BSIs caused by biofilm-forming MRSA strains were more
      likely to be hospital onset [77.9% vs. 60.0%, p = 0.024, OR 2.434, 95% CI 1.11
      5.33) and more frequently occurred in patients with use of invasive devices
      [85.7% vs. 61.2%, p = 0.002, OR 3.879, 95% CI 1.61-8.97]. The other clinical
      features were compared with the clinical outcomes of the two groups and were not
      significant (p > 0.05). CONCLUSION: Biofilm-forming MRSA strains showed higher
      frequency of fnbB gene than biofilm non-forming ones and more incidence rates on
      particular genotypes. And, their patient's features were not significantly
      different between two groups in this study, except for several clinical factors.

PMID- 24298438
TI  - Community-based home healthcare project for korean older adults.
AB  - OBJECTIVES: The aim of this study was to identify the effects of community-based
      home healthcare projects that influence service performances with regard to
      Korean national long-term care insurance services in older adults. METHODS: The
      project's applicants were 18 operational agencies in national long-term care
      institutions in Korea, and participants were care recipients (n = 2263)
      registered in long-term care institutions. We applied our healthcare system to
      the recruited participants for a 3-month period from October 2012 to December
      2012. We measured the community-based home healthcare services such as long-term
      care, health and medical service, and welfare and leisure service prior to and
      after applying the community-based home healthcare system. RESULTS: After the
      implementation of community-based home healthcare project, all community-based
      home healthcare services showed an increase than prior to the project
      implementation. The nutrition management service was the most increased and its
      increase rate was 628.6%. A comparison between the long-term care insurance
      beneficiaries and nonbeneficiaries showed that health and medical services'
      increase rate of nonbeneficiaries was significantly higher than beneficiaries (p
      < 0.001). CONCLUSION: Our community-based home healthcare project might improve
      the service implementation for older adults and there was a difference in the
      increase rate of health and medical services between Korean national long-term
      care insurance beneficiaries and nonbeneficiaries.

PMID- 24298439
TI  - The impact of emergency room utilization by depression patients on medical
      treatment expense in Korea.
AB  - OBJECTIVES: To investigate the determinants of total medical expense for
      depression patients admitted through the emergency room (ER). METHODS: Data were
      selected from the Korean National Health Insurance sample data for 2009. SPSS
      version 18 was used for the statistical analysis such as descriptive analysis,
      correlation analysis, and multiple regression analysis. Data included 1203 cases
      admitted through the ER with ICD-10 codes (F31-F39). RESULTS: In the multiple
      regression analysis, significant variables affecting total payment were gender (p
      < 0.001), age (p < 0.001), main illness (p < 0.001), course of admission to the
      ER (p < 0.05), and length of stay (p < 0.001). CONCLUSION: It is necessary to
      build a long-term program and system for high-risk depression groups.

PMID- 24298440
TI  - Assessment of antioxidant potential, total phenolics and flavonoids of different
      solvent fractions of monotheca buxifolia fruit.
AB  - OBJECTIVES: This study was conducted to investigate the antioxidant potential of
      methanol extract and its derived fractions (hexane, ethyl acetate, butanol, and
      aqueous) of fruits of Monotheca buxifolia (Falc.) Dc., a locally used fruit in
      Pakistan. METHODS: Dried powder of the fruit of M. buxifolia was extracted with
      methanol and the resultant was fractionated with solvents having escalating
      polarity; n-hexane, chloroform, ethyl acetate, n-butanol and the residual soluble
      aqueous fraction. Total phenolic and total flavonoid contents were estimated for
      the methanol and various fractions. These fractions were also subjected to
      various in vitro assays to estimate the scavenging activity for 2,2-diphenyl-1
      picrylhydrazyl (DPPH), 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS), superoxide, hydroxyl, hydrogen peroxide and reductive ability for ferric
      ions and phosphomolybdate assay. RESULTS: The n-butanol, aqueous and methanol
      fractions possessed high amount of phenolics and flavonoids compared with other
      fractions, and subsequently showed a pronounced scavenging activity on DPPH,
      ABTS, superoxide, hydroxyl and hydrogen peroxide radicals and had a potent
      reductive ability on ferric ion and phosphomolybdate assay. There was a found
      significant correlation between total phenolic and flavonoid contents and EC50 of
      DPPH, superoxide, hydrogen peroxide radical and phosphomolybdate assays, whereas
      a nonsignificant correlation was found with the hydroxyl radical and ABTS radical
      assay. CONCLUSION: M. buxifolia fruit can be used as natural antioxidant source
      to prevent damage associated with free radicals.

PMID- 24298441
TI  - Dynamic Integration of Mobile JXTA with Cloud Computing for Emergency Rural
      Public Health Care.
AB  - OBJECTIVES: The existing processes of health care systems where data collection
      requires a great deal of labor with high-end tasks to retrieve and analyze
      information, are usually slow, tedious, and error prone, which restrains their
      clinical diagnostic and monitoring capabilities. Research is now focused on
      integrating cloud services with P2P JXTA to identify systematic dynamic process
      for emergency health care systems. The proposal is based on the concepts of a
      community cloud for preventative medicine, to help promote a healthy rural
      community. We investigate the approaches of patient health monitoring, emergency
      care, and an ambulance alert alarm (AAA) under mobile cloud-based telecare or
      community cloud controller systems. METHODS: Considering permanent mobile users,
      an efficient health promotion method is proposed. Experiments were conducted to
      verify the effectiveness of the method. The performance was evaluated from
      September 2011 to July 2012. A total of 1,856,454 cases were transported and
      referred to hospital, identified with health problems, and were monitored. We
      selected all the peer groups and the control server N0 which controls N1, N2, and
      N3 proxied peer groups. The hospital cloud controller maintains the database of
      the patients through a JXTA network. RESULTS: Among 1,856,454 transported cases
      with beneficiaries of 1,712,877 cases there were 1,662,834 lives saved and 8,500
      cases transported per day with 104,530 transported cases found to be registered
      in a JXTA network. CONCLUSION: The registered case histories were referred from
      the Hospital community cloud (HCC). SMS messages were sent from node N0 to the
      relay peers which connected to the N1, N2, and N3 nodes, controlled by the cloud
      controller through a JXTA network.

PMID- 24298442
TI  - Evaluation and Selection of Multilocus Variable-Number Tandem-Repeat Analysis
      Primers for Genotyping Brucella abortus Biovar 1 Isolated from Human Patients.
AB  - OBJECTIVES: Brucellosis is the most common bacterial zoonosis in the world.
      Multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) is a molecular
      method for genotyping bacterial species. Brucella abortus biovar I was isolated
      from most of the brucellosis-suspected patients in Korea. This study was
      conducted to investigate the ability of various MLVA primers that are used for
      molecular typing B. abortus isolates and for analyzing their epidemiological
      data. METHODS: A total of 80 human isolates of B. abortus biovar I isolated from
      human patients and the reference strain were used for MLVA. Genetic diversity was
      determined by calculating the Simpson's diversity index (DI) of each VNTR locus.
      The Brucella strains were subcultured 30 times to determine the stability of each
      locus. The DNA of the strains cultivated in each passage was extracted and
      subjected to MLVA for further investigation. RESULTS: The 15 VNTR loci were
      selected based on high DI values. The DIs of the 15 VNTR loci showed considerable
      discrimination power ranging from 59% for Bruce 43 to 87% for Bruce 22. Bruce 09,
      Bruce 11, Bruce 16, Bruce 42, and Bruce 43 were confirmed to remain stable in
      vitro among the 15 VNTR loci selected. CONCLUSION: The results of this study
      suggest that the five loci subsets may be a useful epidemiological tool for
      investigating B. abortus biovar 1 outbreak.

PMID- 24298443
TI  - Gastroprotective Potential of Dalbergia sissoo Roxb. Stem Bark against Diclofenac
      Induced Gastric Damage in Rats.
AB  - OBJECTIVES: Dalbergia sissoo Roxb. stem bark possesses anti-inflammatory,
      antipyretic, and antioxidant properties. This plant is used traditionally in the
      Indian system of medicine to treat emesis, ulcers, leucoderma, dysentery, stomach
      complaints, and skin disorders. This study was conducted to evaluate the
      antiulcer effects of D. sissoo stem bark methanol extract (DSME) against the
      diclofenac sodium-induced ulceration in rat. METHODS: The DSME (200 mg/kg and 400
      mg/kg body weight) was orally administered to rats once a day for 10 days in
      diclofenac-treated rats. The gastroprotective effects of DSME were determined by
      assessing gastric-secretory parameters such as volume of gastric juice, pH, free
      acidity, and total acidity. Biochemical studies of gastric mucosa were conducted
      to estimate the levels of nonprotein sulfhydryls (NP-SHs), lipid peroxidation
      [thiobarbituric acid reactive substances (TBARSs)], reduced glutathione (GSH),
      hydrogen peroxide (H2O2), levels of scavenging antioxidants, catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S
      transferase (GST), and myeloperoxidase (MPO). Moreover, adherent mucus content
      and histological studies were performed on stomach tissues. RESULTS:
      Administration of DSME significantly decreased the ulcer index, TBARSs, H2O2, and
      MPO activity in gastric mucosa of the ulcerated rats. Activities of enzymic
      antioxidants, CAT, SOD, GSH-Px, GST and GSH, and NP-SH contents were
      significantly increased with DSME administration in the gastric mucosa of
      diclofenac-treated rats. Volume of gastric juice, total and free acidity were
      decreased, whereas pH of the gastric juice was increased with the administration
      of DSME + diclofenac. Our results show that DSME administration is involved in
      the prevention of ulcer through scavenging of free radicals. Results of
      histopathological studies supported the gastroprotective activities of DSME.
      CONCLUSION: The results of this study showed that DSME exhibit potential
      gastroprotective activity probably due to its antioxidant and cytoprotection
      ability.

PMID- 24298444
TI  - Public health crisis preparedness and response in Korea.
AB  - Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the
      World Health Organization's recommendation, the Republic of Korea has prepared
      and periodically evaluated the plan to respond to various public health crises
      including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral
      drugs covering 26% of the Korean population and runs 519 isolated beds in 16
      medical institutions. The division of public health crisis response in Korea
      Centers for Disease Control and Prevention are in charge of responding to public
      health crises caused by emerging infectious diseases including severe acute
      respiratory syndrome, avian influenza human infection, and pandemic influenza.
      Its job description includes preparing for emerging infectious diseases, securing
      medical resources during a crisis, activating the emergency response during the
      crisis, and fortification of capabilities of public health personnel. It could
      evolve into a comprehensive national agency to deal with public health crisis
      based on the experience of previous national emerging infectious diseases. 

PMID- 24298445
TI  - Introduction of the Republic of Korea-the United States of America's Joint
      Exercise Against Biothreats in 2013: Able Response 13.
AB  - The Republic of Korea (ROK) and the the United States of America (USA) has held
      joint exercises to respond to biothreats in the Korean Peninsula since 2011. The
      exercise was called Able Response (AR) and it aims to coordinate interministerial
      procedures inside Korea and international procedures in requesting the medical
      resources urgently between ROK and USA, and among ROK and the United Nations, and
      nongovernmental organizations. AR13 was a functional exercise with a scenario
      that presumed a series of attack by terrorists, dispersing Bacillus anthracis in
      Seoul. The participants conducted exercises with action cells and using point-to
      point communication system. It was followed by Senior Leadership Seminar
      participated by high-ranking officials in ROK and USA to discuss possible
      collaboration in advance. AR and its following actions will fortify collaboration
      between ROK and USA and enhance the capability of countermeasures against
      biothreats in Korea. 

PMID- 24298447
TI  - Correlates of NNAL levels among nondaily and daily smokers in the college student
      population.
AB  - INTRODUCTION: Recent simultaneous increases in nondaily smoking and decreases in
      daily smoking make the identification of nondaily smokers through biomarker
      measures as well as the relationship of biomarker levels to smoking behaviors
      important topics. However, little is known about biochemical identification and
      carcinogen exposure of nondaily smokers. One tobacco-specific nitrosamine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), has a long half-life, making
      it a useful marker for long-term and intermittent tobacco exposure. Thus, we
      examined correlates of urine NNAL levels among nondaily and daily smokers.
      METHODS: In 2011, we obtained urine samples from 64 current cigarette smokers (37
      nondaily; 27 daily) in the Southeastern US and assessed participants'
      sociodemographics, smoking-related information, and other tobacco use. Our sample
      included 14 participants concurrently using other combustible tobacco products
      and eight concurrently using smokeless tobacco. RESULTS: Of six participants
      smoking for only one day in the past 30, four had detectable NNAL levels; thus,
      two nondaily smokers were excluded from the remainder of the analyses. In
      multivariate analysis, average cigarettes per day on smoking days (B = 23.00, 95%
      Confidence Interval [CI] 13.81, 32.20, P < 0.001) and number of days of smokeless
      tobacco use (B = 17.11, CI 13.53, 20.70, P < 0.001) were associated with NNAL
      levels among nondaily smokers (R2 = 0.234). Multivariate analysis indicated that
      average cigarettes per day (B = 15.83, CI 2.89, 28.76, P = 0.02) was the only
      significant correlate of NNAL levels among daily smokers. We used receiver
      operating characteristic (ROC) analyses to identify a potential urinary NNAL
      (normalized for creatinine) cutoff point of 81.6 pg/mL/g creatinine (88.9%
      sensitivity, 80.0% specificity) to discriminate nondaily from daily smokers.
      Excluding polytobacco-product users from these analyses provided similar results.
      CONCLUSION: Different correlates of NNAL levels exist among nondaily and daily
      cigarette smokers. Urine NNAL demonstrates the potential to be used to
      discriminate nondaily from daily smokers among young adults.

PMID- 24298446
TI  - Prefrontal activation during inhibitory control measured by near-infrared
      spectroscopy for differentiating between autism spectrum disorders and attention
      deficit hyperactivity disorder in adults.
AB  - The differential diagnosis of autism spectrum disorders (ASDs) and attention
      deficit hyperactivity disorder (ADHD) based solely on symptomatic and behavioral
      assessments can be difficult, even for experts. Thus, the development of a
      neuroimaging marker that differentiates ASDs from ADHD would be an important
      contribution to this field. We assessed the differences in prefrontal activation
      between adults with ASDs and ADHD using an entirely non-invasive and portable
      neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naive
      adults with ASDs, 19 drug-naive adults with ADHD, and 21 healthy subjects matched
      for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the
      prefrontal cortex were assessed during a stop signal task and a verbal fluency
      task. During the stop signal task, compared to the control group, the ASDs group
      exhibited lower activation in a broad prefrontal area, whereas the ADHD group
      showed underactivation of the right premotor area, right presupplementary motor
      area, and bilateral dorsolateral prefrontal cortices. Significant differences
      were observed in the left ventrolateral prefrontal cortex between the ASDs and
      ADHD groups during the stop signal task. The leave-one-out cross-validation
      method using mean oxygenated hemoglobin changes yielded a classification accuracy
      of 81.4% during inhibitory control. These results were task specific, as the
      brain activation pattern observed during the verbal fluency task did not
      differentiate the ASDs and ADHD groups significantly. This study therefore
      provides evidence of a difference in left ventrolateral prefrontal activation
      during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared
      spectroscopy may be useful as an auxiliary tool for the differential diagnosis of
      such developmental disorders. 

PMID- 24298448
TI  - Toward a Molecular Classification of Colorectal Cancer: The Role of BRAF.
AB  - Different genetic aberrations of BRAF have been reported in various malignancies.
      BRAF is member of the RAS/RAF/MEK/ERK pathway and constitutive activity of this
      pathway can lead to increased cellular growth, invasion, and metastasis. The most
      common activating BRAF mutation in colorectal cancer is the V600E mutation, which
      is present in 5-15% of all tumors, and up to 80% of tumors with high
      microsatellite instability (MSI) harbor this mutation. BRAF mutation is
      associated with proximal location, higher age, female gender, MSI-H, high grade,
      and mucinous histology, and is a marker of poor prognosis in colorectal cancer.
      The role of BRAF mutation as a predictive marker in respect of EGFR targeted
      treatments is controversial. BRAF V600 selective inhibitors have been approved
      for the treatment of V600 mutation positive metastatic melanoma, but the response
      rates in colorectal cancer are poor. This might be due to innate resistance
      mechanisms of colorectal cancers against the treatment solely targeting BRAF. To
      overcome resistance the combination of treatments, simultaneous inhibition of
      BRAF and MEK or PI3K/mTOR, might emerge as a successful therapeutic concept. 

PMID- 24298450
TI  - Embryological basis and clinical correlation of the rare congenital anomaly of
      the human gall bladder: - "the diverticulum" - a morphological study.
AB  - BACKGROUND: Diverticulum of the human gall bladder is an important but distinct
      anatomical entity with significant clinical implications. It is one of the rarest
      congenital anomalies of the gall bladder being rarely discussed in literature.
      This article details the morphology of the diverticula found, along with the
      embryological basis and clinical significance of this important anatomical and
      clinical entity. AIM: To study the diverticula found, with respect to their
      morphology, and ascertain whether they were of congenital or acquired variety.
      Setting and Designs: The present study is a retrospective study carried on
      hundred cadavers during undergraduate dissection, in the Department of Anatomy,
      Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, and Department of
      Anatomy, Subharti Medical College , Meerut during a four year period i.e. 2008
      2012 after obtaining necessary permission from institutional ethical committee.
      MATERIAL AND METHODS: Hundred gall bladder specimens collected from 10% formalin
      fixed cadavers were studied in detail with regard to their number, position,
      shapes dimensions and histology. RESULTS: Nine, congenital (true) diverticula
      were found in one hundred gall bladder specimens. The diverticula were of various
      shapes and dimensions. They formed pouches on the luminal surface of the gall
      bladder. Diagnosis of congenital diverticulum was confirmed by histology.
      CONCLUSION: In this cadaveric study, solitary diverticulum was found in nine (9%)
      specimens out of one hundred specimens. Association of diverticulum with non
      specific prolonged ailments, acalculus cholecystitis, cholecystitis and
      cholelithiasis, recurrent cholangitis and carcinoma of gallbladder has been
      reported in literature. This important anatomical as well as clinical entity
      poses challenges for radiologists and laparoscopic surgeons during interventional
      procedures and also should be differentiated from other types of congenital
      anomalies and pathological states of gall bladder.

PMID- 24298449
TI  - Metal-dependent gene regulation in the causative agent of Lyme disease.
AB  - Borrelia burgdorferi (Bb) is the causative agent of Lyme disease transmitted to
      humans by ticks of the Ixodes spp. Bb is a unique bacterial pathogen because it
      does not require iron (Fe(2+)) for its metabolism. Bb encodes a ferritin-like Dps
      homolog called NapA (also called BicA), which can bind Fe or copper (Cu(2+)), and
      a manganese (Mn(2+)) transport protein, Borrelia metal transporter A (BmtA); both
      proteins are required for colonization of the tick vector, but BmtA is also
      required for the murine host. This demonstrates that Bb's metal homeostasis is a
      critical facet of the complex enzootic life cycle between the arthropod and
      murine hosts. Although metals are known to influence the expression of virulence
      determinants during infection, it is unknown how or if metals regulate virulence
      in Bb. Recent evidence demonstrates that Bb modulates the intracellular Mn(2+)
      and zinc (Zn(2+)) content and, in turn, these metals regulate gene expression
      through influencing the Ferric Uptake Regulator (Fur) homolog Borrelia Oxidative
      Stress Regulator (BosR). This mini-review focuses on the burgeoning study of
      metal-dependent gene regulation within Bb. 

PMID- 24298451
TI  - Estimation of total Length of Femur From Its Fragments in South Indian
      Population.
AB  - INTRODUCTION: Establishment of identity of deceased person also assumes a great
      medicolegal importance. To establish the identity of a person, stature is one of
      the criteria. To know stature of individual, length of long bones is needed. AIMS
      AND OBJECTIVES: To determine the lengths of the femoral fragments and to compare
      with the total length of femur in south Indian population, which will help to
      estimate the stature of the individual using standard regression formulae.
      MATERIAL AND METHODS: A number of 150, 72 left and 78 right adult fully ossified
      dry processed femora were taken. The femur bone was divided into five segments by
      taking predetermined points. Length of five segments and maximum length of femur
      were measured to the nearest millimeter. The values were obtained in cm [mean+/
      S.D.] and the mean total length of femora on left and right side was measured.
      The proportion of segments to the total length was also calculated which will
      help for the stature estimation using standard regression formulae. RESULTS: The
      mean total length of femora on left side was 43.54 +/- 2.7 and on right side it
      was 43.42 +/- 2.4. The measurements of the segments-1, 2, 3, 4 and 5 were 8.06+/-
      0.71, 8.25+/- 1.24, 10.35 +/- 2.21, 13.94 +/- 1.93 and 2.77 +/- 0.53 on left side
      and 8.09 +/- 0.70, 8.30 +/- 1.34, 10.44 +/- 1.91, 13.50 +/- 1.54 and 3.09 +/-
      0.41 on right side of femur. CONCLUSION: The sample size was 150, 72 left and 78
      right and 'p' value of all the segments was significant (<0.001). When comparison
      was made between segments of right and left femora, the 'p' value of segment-5
      was found to be <0.001. Comparison between different segments of femur showed
      significance in all the segments.

PMID- 24298452
TI  - Nimesulide induced histopathological changes in the vas deferens of mice.
AB  - AIM: Nimesulide, a preferential COX-2 inhibitor has 20 times more selectivity
      towards COX-2 than that of COX-1. COX-2 selective inhibitors cause frequent
      nephrotoxicity and hepatotoxicity following their usage. This proposes a
      physiological role of COX-2 in kidney and liver. Not much attention has been
      focused on the role of COX-2 with respect to reproduction especially in male
      reproduction, and the available information is scanty. AIMs and Objectives: The
      present study aims to investigate the adverse effects of nimesulide in the vas
      deferens thereby indirectly assess the role of COX-2 in male reproductive tract.
      MATERIAL AND METHODS: Nimesulide was administered orally and the animals were
      maintained for different time periods prior to sacrifice. RESULTS: The vas
      deferens of nimesulide treated mice showed extensive histopathological changes
      such as vacoulation and exfoliation of cells in the epithelial layer. CONCLUSION:
      Nimesulide administration leads to cytotoxic effects suggestive of apoptosis in
      the vas deferens of mice.

PMID- 24298453
TI  - Correlation of 2 hours and 24 hours creatinine clearance in renal donors after
      unilateral nephrectomy.
AB  - BACKGROUND: The kidney performs numerous specialised functions in an effort to
      maintain constancy of the internal composition of body fluids. AIM: This study
      was done to ascertain the feasibility of estimating creatinine clearance as an
      outpatient procedure over a 2 hours period instead of doing the study over a 24
      hours period. MATERIAL AND METHODS: Eighteen renal donors, Twelve females and Six
      males, who were closely related to recipients, were chosen. This study was done
      on renal donors who attended the Nephrology Department of Rajiv Gandhi Government
      General Hospital, Madras Medical College, Chennai-03 India. To estimate
      creatinine clearance in 24 hours urine, 24 hours urine sample was collected from
      9 am on the first day to 9 am on the next day, after first emptying the bladder.
      Then, creatinine clearance was calculated by using standard formula, CC=UV/ Pt X
      1.73m(2)/BSA of the individual. RESULTS: There was no significant differences in
      mean creatinine clearance values by collecting 2 hours and 24 hours urine samples
      from renal donors in different stages of post nephrectomy period. It has been
      shown that 2 hours collection of urine sample is as good as 24 hours urine sample
      for estimating creatinine clearance. CONCLUSION: Hence it was proved that
      measurement of creatinine clearance could be done as an outpatient procedure, as
      the patient needed only 2 hours of hospital stay.

PMID- 24298454
TI  - Dyslipidaemic changes in women with subclinical hypothyroidism.
AB  - BACKGROUND: In overt hypothyroidism, many lipid abnormalities have been
      documented. This study was intended to demonstrate the levels of lipid in women
      with subclinical hypothyroidism (SH). MATERIAL AND METHODS: This was a case
      control study which was done at referral Centre in Chennai. Women with
      subclinical hypothyroidism and euthyroid women attending our master health
      checkup clinic were enrolled in this study.Their lipid profile, fasting blood
      sugar, T3,T4 and TSH levels were measured. In subclinical hypothyroidism, various
      parameters were compared. RESULTS: Thirty euthyroid and 30 age matched
      subclinical hypothyroid women were enrolled in this study. There were significant
      dyslipidaemic changes is SH women as compared to euthyroid controls. Serum total
      cholesterol and triglyceride levels were significantly higher as compared to
      those in controls. LDL levels were higher is SH women, but did not reach
      statistical significance and lower levels of HDL were noticed in SH subjects as
      compared to those in euthyroid women. A positive association was also reported
      between serum TSH and lipid parameters in our study group. CONCLUSION: SH, the
      earliest form of thyroid failure, has negative metabolic effects on the affected
      subjects.SH could be one of the causes of secondary hyperlipidaemia and should be
      viewed as an independent risk factor for atherosclerosis, along with obesity,
      hypertension, diabetes, etc.

PMID- 24298455
TI  - Acute lung function response to dust in street sweepers.
AB  - BACKGROUND: Sweepers are chronically exposed to dust raised during sweeping. Dust
      is regarded as the most influential agent and it is perceived as a frequent cause
      of respiratory system illness and may cause acute and chronic lung function
      impairment. AIMS: The aim of this study was to determine the acute lung function
      changes in sweepers exposed to dust generated from street sweeping. MATERIAL AND
      METHODS: This study was conducted in central Karnataka, India, on 25 female
      sweepers and 25 healthy female control subjects who were comparable in age,
      height and weight. The pulmonary function test was performed in controls,
      sweepers before and after sweeping, by using RMS medspiror and results were
      compared by Student's unpaired 't' test. RESULTS: The results showed a
      significant reduction in percent predicted values and mean values of FVC, FEV1,
      PEFR, FEF25-75% and FEF 200-1200 between sweepers and their matched controls.
      Pulmonary function after sweeping also showed a significant decrease.
      CONCLUSIONS: On comparing the pulmonary functions of sweepers before and after
      sweeping, it was concluded that inhalation of dust acutely affected the lung
      function of sweepers in India and that sweepers were at a risk of developing
      occupation related lung function impairment. We recommend that the workers should
      use protective face masks and do wet sweeping instead of dry sweeping during
      sweeping activity.

PMID- 24298456
TI  - Cardiovascular reactivity to stressors in Indian young adults with normotensive
      parents.
AB  - BACKGROUNDS AND OBJECTIVES: Stress-induced increase in heart-rate and blood
      pressure is termed cardiovascular reactivity (CVR). Various studies are designed
      to monitor the CVR and use different types of experimental stressors. We have
      compared the CVR to three different stressors used in CVR based studies (cold
      pressor task, hand grip test, and video game) to identify the best suited
      stressor for any study design. MATERIAL AND METHODS: The study was conducted on
      82 (38 female) young Indian adults with normal resting basal parameters and
      normotensive parents. Each volunteer was subjected to three stressors: cold
      pressor task (CPT), hand grip test (HGT), and video game (VG). The CVR to the
      three stressors was compared amongst female subjects and amongst male subjects by
      ANOVA, and between female and male subjects by unpaired Student's t-test.
      RESULTS: Maximum CVR was obtained to HGT, while maximum gender difference in CVR
      was obtained in case of CPT. Heart rate and blood pressure changes obtained on
      playing VG were not statistically significant. CONCLUSION: When the purpose of
      research is to generate maximum possible CVR, we suggest the use of HGT; while if
      the purpose of the research is to study gender related differences, the use of
      CPT would be more appropriate. Unlike young adults of Western countries, VG is
      not perceived as a challenging task or stressor by young Indian adults and
      produces little change in heart rate and blood pressure.

PMID- 24298457
TI  - Effect of yoga on autonomic functions and psychological status during both phases
      of menstrual cycle in young healthy females.
AB  - CONTEXT: Premenstrual stress affects 75% of women of childbearing age and yoga
      has been found to be beneficial in many psycho-somatic disorders. AIMS: To
      investigate the effect of integrated yoga on autonomic parameters and
      psychological well-being during both pre and post phases of menstrual cycle in
      healthy young female subjects. SETTINGS AND DESIGN: Present study is a randomized
      control trial and was conducted in the Department of Physiology, Lady Hardinge
      Medical College, New Delhi, India. MATERIAL AND METHODS: Fifty apparently healthy
      females in the age group of 18-20 years were randomized into two groups: Group I
      (n=25) consisted of subjects who practiced yoga 35-40 minutes per day, six times
      per week for the duration of three menstrual cycles. Training was given by
      qualified yoga instructor. Group II (n=25) subjects acted as controls. Following
      parameters were recorded at the beginning and after completion of three menstrual
      cycles in all the subjects: Height, weight (BW), Resting Heart Rate (HR), Resting
      Systolic (SBP) and Diastolic Blood Pressure (DBP), parasympathetic reactivity
      tests including Expiration-Inspiration Ratio (E: I ratio) and 30:15 ratio,
      sympathetic reactivity tests including BP changes due to Isometric Hand Grip
      (IHG) exercise, and Cold Pressor Test (CPT). Assessment of psychological status
      was done by administering DIPAS (Defense Institute of Physiology and Allied
      Sciences) inventories of Anger self report scale, Trait Anxiety, Sense of well
      being and Depression scale. STATISTICAL ANALYSIS: Intra-group comparison of
      physiological parameters was done by using paired 't' test, whereas intra-group
      comparison of non-parameteric data such as scores of anxiety, depression, anger
      and sense of well-being was done by Wilcoxon signed-rank test. Inter-group
      comparison of parameters was done by Students 't' test for parametric tests and
      Mann-Whitney 'U' test for non-parameteric tests. RESULTS: There was significantly
      higher BW, resting SBP, DBP, sympathetic activity and blunting of parasympathetic
      reactivity and also, significantly higher scores of anger, depression, anxiety
      and decreased score of well-being in premenstrual phase as compared to
      postmenstrual phase in both the groups in initial cycle. There was significantly
      higher percentage decrease in BW, HR, SBP & DBP in yoga group as compared to
      control group in both the phases from initial to second and onwards between
      second and third menstrual cycle. Also, decrease in anger, depression and anxiety
      and increase in well-being score was significant in yoga group as compared to
      control group from initial to second and third cycle in premenstrual phase while
      the change was significant only in depression score in postmenstrual phase.
      CONCLUSION: Our study shows that there was significant alteration of autonomic
      functions and psychological status in premenstrual phase when compared with
      postmenstrual phase in young healthy females. Also, regular practice of yoga has
      beneficial effects on both phases of menstrual cycle by bringing
      parasympathodominance and psychological well-being probably by balancing neuro
      endocrinal axis.

PMID- 24298458
TI  - A study of serum malondialdehyde and cytokine in tuberculosis patients.
AB  - INTRODUCTION: Tuberculosis (TB) is a common and a deadly infectious disease which
      is caused by Mycobacterium tuberculi. Inflammatory cytokines play an important
      role during the course of the disease and they may be responsible for tissue
      damage which is caused by lipid peroxidation. METHOD: The present study was
      conducted in the Department of Biochemistry and patients were selected from
      Department of TB and Chest Sri Aurobindo Institute of Medical Sciences and also
      from Manorama Raje Tuberculosis Hospital, Indore. 32 healthy controls and 35
      pulmonary TB patients were compared initially for their serum Malondialdehyde
      (MDA) and tumour necrosis factor alpha (TNF alpha) levels. Serum TNF alpha and
      MDA levels were correlated. RESULT: TNF alpha and MDA levels in serum were
      significantly increased (p<0.001) in pulmonary tuberculosis patients as compared
      to those of controls. Increased Serum TNF alpha was positively correlated to MDA
      levels and it was found to be statistically not significant (correlation
      coefficient r =0.282,p> 0.05 ). CONCLUSION: The present study supports the view
      that there may be a link between lipid peroxidation and cytokine response and
      relative roles of cytokines and lipid peroxidation in the pathogenesis of
      tuberculosis.

PMID- 24298459
TI  - A Study of Inflammatory Status in Nephropathy Patients with History of Type-II
      Diabetes Mellitus Undergoing Haemodialysis.
AB  - INTRODUCTION AND OBJECTIVE: Diabetic nephropathy is one of the leading cause of
      chronic kidney failure. Local vascular inflammation is increased in diabetes
      mellitus (DM), which results in higher burden of microvascular and macrovascular
      complications. The present study was carried out to assess the importance of
      inflammatory status in nephropathy patients with Type-II DM. METHODOLOGY: Eighty
      diagnosed cases of type II DM who had end stage renal disease (Nephropathy Stage
      5) were selected for the study, they were further divided equally into 2 sub
      categories; Group I (patients who were undergoing haemodialysis) and Group II
      (patients who were not undergoing haemodialysis). The control group comprised of
      40 individuals who were age and sex matched healthy individuals. Inflammatory
      status was assessed by estimating serum C-reactive protein (CRP) and serum
      albumin. RESULTS: A significant increase in serum CRP and a significant decrease
      in serum albumin were seen in test group- I and test group-2 as compared to
      controls. There was a positive correlation between serum albumin and GFR with
      r=0.904 in the Test Group-I and r=0.946 in Test Group-II. A negative correlation
      was observed between serum CRP and GFR r= -0.597 in Test Group-I and with r= 
      0.6231 in Test Group-II. Also, the correlation between CRP and albumin showed a
      negative trend with r= -0.848 in Test Group-I and with r= -0.78 in Test Group-II.
      CONCLUSION: Microinflammation is a common finding in haemodialysis patients who
      have a history of nephropathy with Type-II diabetes mellitus. With a proper
      knowledge on factors which lead to this microinflammation, we can employ
      preventive strategies for a better management of Type-II diabetic nephropathy
      patients and thereby, for improving their survival.

PMID- 24298460
TI  - A study of oxidative stress biomarkers and effect of oral antioxidant
      supplementation in severe acute malnutrition.
AB  - BACKGROUND: Malnutrition represents one of the most severe health problems in
      India. Free radicals play an important role in immunological response, which
      induces the oxidative surplus in severe acute malnutrition. Severe dietary
      deficiency of nutrients leads to increased oxidative stress in cellular
      compartments. AIM: The goal of this study was to inspect impact of oxidative
      stress in the form of serum malondialdehyde as product of lipid peroxidation,
      vitamin E, zinc and erythrocyte superoxide dismutase in patients with severe
      acute malnutrition. MATERIAL AND METHODS: Sixty severe acute malnutrition
      patients were studied before and after supplementation of antioxidants for one
      month, and their status were compared with those of 60 age and sex matched
      healthy controls. The level of serum MDA was analyzed by the Kei Satoh method,
      serum vitamin E concentration was measured by Baker and Frank Method, serum zinc
      was measured by using Atomic Absorption Spectrophotometer (AAS) and erythrocyte
      superoxide dismutase was measured by Kajari Das Method. RESULTS: Significantly
      increased levels of serum malondialdehyde (p<0.001) were found in the patients as
      compared to those in controls, and significant depletions were found in the
      levels of serum vitamin E, zinc and erythrocyte superoxide dismutase in patients
      with severe acute malnutrition as compared to those in controls. After
      supplementation of antioxidants for one month, the levels of malondialdehyde were
      found to be decreased significantly (p<0.001) and zinc and erythrocyte superoxide
      dismutase capacity levels were increased significantly (p<0.05). Also, there was
      a non-significant (p>0.05) increase in vitamin E levels as compared to those
      before supplementation results. CONCLUSION: Harsh deficiency of various nutrients
      in severe acute malnutrition leads to generation of heavy oxidative stress. These
      effects may be minimized with supplementation of antioxidants.

PMID- 24298461
TI  - Apolipoprotein e gene polymorphism and its effect on plasma lipids in
      arteriosclerosis.
AB  - BACKGROUND & OBJECTIVES: Myocardial infarction and stroke are leading causes of
      death worldwide. Primarily, arteriosclerosis is responsible for these events.
      There is a strong family history suggesting a genetic cause. Apolipoprotein E
      (apo E) plays an important role in lipid metabolism. Apo E is polymorphic with
      three isoforms, ApoE2, ApoE3 and ApoE4; which translate into three alleles of the
      gene. Its polymorphism may be a risk determinant of atherosclerosis. METHODS:
      Lipoprotein concentrations were studied, in 100 myocardial infarction and 50
      cerebrovascular stroke subjects and compared with age and sex matched controls.
      Genotypes for apo E isoforms (E2, E3, and E4) for all above subjects and age and
      sex matched controls were determined by Multiplex Amplification Refractory
      Mutation System PCR. RESULTS: There were statistically significant higher values
      of serum total cholesterol and LDL cholesterol in study group, as compared to
      control group. Study of Apo E isoforms revealed higher proportion of E4 allele in
      the study group as compared to control group. The occurrence of each allele
      frequency in study and control group was E4E4: 28.66% and 16.0%, E3E3: 39.33% and
      56.66%, E4E3: 14.66% and 9.33%, E3E2: 8.66% and 10.66%, E4E2: 4.66% and 2.66% &
      for E2E2: 4.0% and 4.66% respectively. INTERPRETATION & CONCLUSION: There were
      significantly higher levels of serum total cholesterol, LDL cholesterol and
      triglyceride with E4 allele; when compared with in the study group and between
      study group and control group. Apo E polymorphism influences serum lipid levels
      and is an independent risk determinant of arteriosclerosis.

PMID- 24298462
TI  - Effects of Areca Nut Extracts on Phagocytosis of Actinobacillus actinomycete
      mcomitans ATCC 33384 by Neutrophils in Patients with Chronic Periondontitis.
AB  - BACKGROUND & OBJECTIVE: A higher prevalence of periodontal disease among areca
      nut chewers than non chewers has been demonstrated. Neutrophils, the first line
      of defence mechanism against microbial infection play an important role in
      maintaining the periodontal health. In this context our aim was to evaluate the
      effects of areca nut extracts on phagocytic activity by neutrophils isolated from
      gingival crevicular washing of healthy subjects and patients with chronic
      periodontitis. MATERIAL AND METHODS: Sample size consisted of a total of 60
      subjects which were divided into two groups of 30 each. Group I consisted healthy
      subjects and Group II consisted clinically diagnosed cases of chronic
      periodontitis. Neutrophils isolated from gingival crevicular washings of both
      groups were treated with aqueous extracts of ripe areca nut (rANE) and tender
      areca nut (tANE) and examined for their effect on cellular viability of
      neutrophils using typan blue exclusion assay. The possible/ ableffects on the
      phagocytic activity of neutrophils against a periodontal pathogen Aggregatibacter
      actinomycetemcomitans(ATCC 33384) was determined by using microscopic method.
      RESULTS: Both rANE and tANE affected the phagocytic activity by neutrophils in
      healthy and patients with chronic periodontitis. Ripe areca nut extract has
      altered the neutrophil functions more than tender areca nut in both the groups.
      There was no difference seen in the cell viability of neutrophils when treated
      with rANE and tANE in both the groups (p> 0.05). CONCLUSION: Both ripe and tender
      arecanut extract affected the neutrophil function in healthy and patients with
      chronic periodontitis. Ripe arecanut extract significantly altered the
      neutrophils functions more than tender areca nut extract. Thus, alterations in
      these functions of neutrophils may lead to signs of clinical diseases associated
      with areca chewing.

PMID- 24298463
TI  - The spectrum and aetiology of mycotic infections from a tertiary care hospital
      from Western part of India.
AB  - BACKGROUND: In the past few years, there has been an increase in infections
      caused by fungal aetiology. This is mainly due to increase in sizes of
      populations which are at risk. Also, fungi which were previously considered as
      non-pathogenic have been increasingly implicated. Hence, this study was taken up.
      AIM: To assess the magnitude of mycotic infections in this set up. To assess the
      spectrum of fungi which are involved in various infections. MATERIAL AND METHODS:
      Total 704 samples taken over two and half period were included. They consisted of
      various samples like sputum, blood, urine, sterile body fluids, corneal
      scrapings. These were processed by conventional mycological techniques. These
      included direct microscopy after Gram staining and KOH mount, culture on
      Sabouraud's dextrose agar (SDA), corn meal agar, brain heart infusion (BHI),
      brain heart infusion agar (BHIA) and others, as required. For non-albicans
      Candida, the automated Vitek 2 C system was used. Various moulds and yeasts were
      identified up to genus level and species level. RESULTS: Of 704 samples, 336
      (48%) were positive for fungal culture. Of these, 244 isolates were yeast like
      fungi, 81 were moulds, 7 were yeasts and 4 were dimorphic. Among blood stream
      infections, non-albicans Candida were the commonest isolates. In the urine
      samples, C. albicans was the commonest isolate. From corneal scrapings, only
      moulds and dimorphic fungi were isolated. CONCLUSION: Incidence of non- albicans
      Candidal infections is increasing. Culture and identification of mycotic
      infections is essential for commencement of suitable antifungal therapy.

PMID- 24298464
TI  - Enteric Parasitic Infections in Relation to Diarrhoea in HIV Infected Individuals
      with CD4 T Cell Counts <1000 Cells/MUl in Chennai, India.
AB  - AIM: This study was conducted to estimate the prevalence of enteric parasites in
      HIV patients in Chennai and to correlate with CD4 counts and diarrhoeal status.
      MATERIAL AND METHODS: Faecal specimens from 100 HIV infected individuals with CD4
      < 1000/MUl were screened for enteric parasites with wet mounts, modified acid
      fast stain for coccidian parasites, modified trichrome stain for Microsporidia,
      before and after the stool concentration. Agar plate culture for Strongyloides
      was put up. Chi-square and ANOVA tests were used for statistical analysis.
      RESULTS: Study group comprised of 38 subjects with acute diarrhoea, 30 with
      chronic diarrhoea (> 2 weeks) and remaining 32 without diarrhoea. Enteric
      parasites were detected in 33% of subjects; Isoapora belli (21) being the
      commonest followed by E.histolyt/Entamoeba dispar (5), Entamoeba coli (2),
      Cryptosporidium spp (2), Hookworms (2), Strongyloides stercoralis (2), Giardia
      lamblia (1) and Microsporidium spp (1). There was a significant inverse relation
      between CD4 counts and duration of diarrhoea. Opportunistic parasites were
      isolated from the subjects with wide range of CD4 counts and different diarrhoeal
      status but most commonly from chronic diarrhoea patients. CONCLUSION: The
      prevalence of intestinal parasitic infections in HIV patients is high in Chennai,
      India, especially at CD4 <1000/MUl, I.belli infection being the commonest.
      Routine screening of all HIV patients with low CD4 counts for coccidian parasitic
      infections by using simple stool microscopic techniques can help in early
      diagnosis and treatment.

PMID- 24298465
TI  - Water borne hepatitis a and hepatitis e in malwa region of punjab, India.
AB  - INTRODUCTION: Hepatitis-A virus infection (HAV) and Hepatitis E virus infection
      (HEV) are faecally contaminated water borne infection of great public interest in
      developing countries. HAV has a world-wide /dablestribution and affects infant
      and young children in developing countries and its epidemics are not very common.
      HEV is restricted to tropical countries and affects older children and young
      adults and its epidemics are common. Studies suggested that HEV is etiologically
      responsible for 10%-95% of admitted cases of hepatitis. Exposure rates over a
      period of time are different in different parts of the country and in different
      socio-economic groups. Aim of the study 1. To study the prevalence of HAV and HEV
      in the outbreak of hepatitis in certain areas of Malwa region of Punjab, India.
      2. To determine the age specific prevalence rates of HAV and HEV. 3. To determine
      any change in the epidemiology of these infections. MATERIAL AND METHODS: This
      study was conducted in the Department of Microbiology in GGMC and Hospital
      Faridkot, A leading Tertiary care hospital and the major referral centre of malwa
      region of Punjab,India. Collection and Serological Tests: 1.Venous blood samples
      of patients of acute hepatitis were taken. 2.Relavent information regarding their
      Age, Sex Education, Socio-economic status, personal and community hygiene were
      recorded. All of the sera were screened for IgM Antibody to HEV and HAV using IgM
      capture ELISA Kit (ASIA-LION Biotechnology for HEV and GENERAL BIOLOGICAL
      CORPORATION for HAV ) in accordance with the manufacturer's instructions. Result
      and Conclusion : 1.The outbreak was due to hepatitis A &E virus(HEV predominating
      resulting from fecal contamination of drinking water). 2.Hepatitis E is more
      widely prevalent 3.There is a change in the epidemiology of HAV so,more cases are
      seen in age group of more than 20 years.

PMID- 24298466
TI  - In-vitro Inhibition of Biofilm Formation in Candida albicans and Candida
      tropicalis by Heat Stable Compounds in Culture Filtrate of Aspergillus flavus.
AB  - BACKGROUND: Invasive candidiasis, caused mostly by Candida albicans and C.
      tropicalis is one of the most common causes of bloodstream infection with a
      substantial attributable mortality. This disease is associated with formation of
      structured, multilayered microbial communities known as biofilms over indwelling
      devices. Treatment is rendered difficult owing to factors like poor drug
      penetration through biofilms and high cost of the available antifungal drugs.
      Hence there is imminent need of developing low-cost natural compounds inhibiting
      Candidal biofilm formation in vitro. Organohalgen compounds derived from crude
      culture filtrate of Aspergillus flavus have been documented to impair in vitro
      Candidal survival. AIM: We aimed to detect the effect of preheated and unheated
      crude culture filtrate of Aspergillus flavus on biofilm formation of Candida
      albicans and C. tropicalis in vitro. Setting and Designs: Ours was a laboratory
      based observational study with clinical isolates of the microorganisms selected
      randomly. MATERIAL AND METHODS: In this study, we showed for the first time by
      microtitre plate method that heat stable compounds which were present in
      preheated and unheated culture filtrates of Aspergillus flavus inhibited biofilm
      formation of Candida albicans and C. tropicalis and also lipase activities of
      these pathogens, and filtrate was non-toxic on human cell line as checked
      microscopically. STATISTICAL ANALYSIS USED: Z-test of significance was used to
      calculate significant difference between Candidal biofilm formation in normal
      liquid medium and culture filtrate, respectively. RESULTS AND CONCLUSION: Heat
      stable compounds present in culture filtrate of Aspergillus flavus inhibit
      biofilm formation of Candida albicans and C. tropicalis and also in-vitro lipase
      activity of these pathogens and could pave the way for development of low-cost
      alternatives to treat invasive candidiasis.

PMID- 24298467
TI  - Changing Trend in the Antibiotic Resistance Pattern of Pseudomonas Aeruginosa
      Isolated from Wound Swabs of Out-Patients and in-Patients of a Tertiary Care
      Hospital.
AB  - CONTEXT: Pseudomonas aeruginosa is the most common gram negative bacteria
      associated with nosocomial infections. Active surveillance of trends in
      antibiotic resistance of P. aeruginosa is necessary for the selection of
      appropriate antimicrobial agent for empirical therapy. AIM: To assess the rates
      of antibiotic resistance and multidrug resistance among P. aeruginosa isolates
      and to observe the trend in its resistance pattern over a period of 5 years.
      MATERIALS AND METHODS: Pseudomonas aeruginosa isolated from wound swabs during
      January to June 2007 and January to June 2012 were included in the study.
      Isolates were identified by conventional tests and antibiotic susceptibility was
      determined by disc diffusion method according to CLSI guidelines. RESULTS: A
      total of 307 Pseudomonas aeruginosa isolates were included in the study. Among
      these isolates, 165 were isolated during Jan-June 2007 and 142 were isolated
      during Jan-June 2012. Among in-patients, there was a significant reduction in
      resistance rates of the isolates to ciprofloxacin (49% to 33%), ceftazidime (50%
      to 33%), meropenem (35% to 19%) and imipenem (28% to 14%) in 2012. Similarly, the
      rate of MDR Pseudomonas aeruginosa among the in-patients decreased from 37.9% in
      2007 to 23.7% in 2012 (p value 0.0241). There was no significant difference in
      the resistance rates of the isolates from out-patients during the two study
      periods. CONCLUSION: There was a significant decreasing trend in the resistance
      rates of the isolates to ciprofloxacin, ceftazidime, meropenem and imipenem.
      Reduction in the use of ciprofloxacin could be probable reason for the decreased
      resistance among P. aeruginosa isolates, which needs to be further investigated.

PMID- 24298468
TI  - Prevalence and antibiogram of Extended Spectrum beta-Lactamase (ESBL) producing
      Gram negative bacilli and further molecular characterization of ESBL producing
      Escherichia coli and Klebsiella spp.
AB  - BACKGROUND AND OBJECTIVES: Resistance to a wide variety of common antimicrobials
      has made the proliferation of Extended spectrum beta-lactmase (ESBL) producing
      strains a serious global health concern that has complicated treatment
      strategies. The high proportion of ESBL producers among the Enterobacteriaceae
      and the complex molecular epidemiology with diverse types of ESBL genes are
      alarming. This study was undertaken to identify ESBL production in various Gram
      negative bacilli isolated and to further characterize ESBL producers among
      Escherichia coli and Klebsiella spp by PCR, which were initially screened by
      phenotypic method. MATERIALS AND METHODS: A total of 722 isolates of Gram
      negative bacilli were isolated. Presence of ESBL positivity was detected using
      the double disk synergy test (DDST). Their antibiogram was studied. PCR analysis
      for beta-lactamase (bla) genes of the family TEM, SHV and CTX-M was also carried
      out using designed primers in 20 ESBL isolates each of Escherichia coli and
      Klebsiella spp. RESULTS: Among 722 Gram negative bacilli isolated 379 (52.49%)
      were ESBL producers. The major source of ESBL producers were respiratory tract
      samples, highest ESBL production was observed in Klebsiella sp. (67.04%).
      Resistance to multiple classes of antibiotics was observed among ESBL producers.
      Among ESBL producing genes prevalence of bla-CTX-M (82.5%) was highest, followed
      by bla-TEM (67.5%) and bla-SHV (57.5%) in the present study. The frequency of
      ESBL producing strains among clinical isolates has been steadily increasing.
      Advance drug resistance surveillance and molecular characteristics of ESBL
      isolates is necessary to guide the appropriate and judicious antibiotic use.

PMID- 24298469
TI  - Nosocomial Infections and Drug Susceptibility Patterns in Methicillin Sensitive
      and Methicillin Resistant Staphylococcus aureus.
AB  - AIM: Staphylococcus aureus is one of the leading causes of nosocomial infections
      and is known for its ability to develop resistance to antibiotics. The drug
      susceptibility pattern of Methicillin Sensitive S. aureus (MSSA) and Methicillin
      Resistant S. aureus (MRSA) may vary. AIMs and Objectives: This study was carried
      out to determine and compare the drug susceptibility patterns in nosocomial MSSA
      and MRSA. MATERIAL AND METHODS: The study was conducted between September 2009
      and August 2011. Standard conventional methods were used for the isolation and
      identification of S. aureus. MRSA was identified by the cefoxitin (30 MUg) disk
      method. Antibiotic susceptibility test was done using Kirby-Bauer disk diffusion
      method and the interpretation of the results was done using CLSI guidelines.
      RESULTS: Out of 685 strains of S. aureus studied, 173(25.25%) were MRSA and 512
      (74.25%) were MSSA. Out of 173 MRSA strains, 114(65.89%) were isolated from pus,
      22(12.71%) from vaginal swab, 18(10.40%) from central catheter tip and the
      remaining from other specimens. All isolates were susceptible to vancomycin and
      least number of isolates were susceptible to penicillin. MRSA displayed
      significantly higher resistance to other antibiotics. 45.7% of MRSA strains were
      resistant to clindamycin, 64.7% to ciprofloxacin, 87.3% to cotrimoxazole, 54.3%
      to erythromycin, 17.3% to gentamicin, 16.8% to netilmycin, and 58.38% to
      tetracycline. Inducible clindamycin resistance was detected in 37 (21.38%)
      strains of MRSA. CONCLUSION: Nosocomial infections caused by MRSA is a
      significant problem. MRSA and MSSA differ with their susceptibility to
      antibiotics. All MRSA isolates in our hospitals were susceptible to vancomycin.
      Proper selection of the antibiotics based on antibiotic susceptibility test
      results is needed for effective treatment and prevention of emergence of
      resistance in MRSA and MSSA.

PMID- 24298470
TI  - Do Health Professionals have Positive Perception Towards Consumer Reporting of
      Adverse Drug Reactions?
AB  - AIM: The aim of this study was to evaluate the perceptions of general
      practitioners (GPs) and community pharmacists (CPs) in Penang, Malaysia, towards
      consumer reporting of Adverse Drug Reactions (ADRs). METHODOLOGY: A cross
      sectional mail survey was adopted for the performance of the study. Survey
      questionnaires were sent to 192 CPs and 400 GPs in the state of Penang, Malaysia.
      Reminders were sent to all the non-respondents after 3 weeks of the initial
      mailing. Data which were collected from the questionnaires were analyzed by using
      the Statistical Package for Social Science (SPSS), version 15. The Chi-square
      test was used to determine as to whether there was any significant difference
      between expected and observed frequencies at the alpha level of 0.05. RESULTS:
      Only 104 respondents (47 CPs and 57 GPs) returned the survey, with a response
      rate of 18.0%- a figure which could be considered to be low. This study indicated
      that GPs and CPs were aware about the importance and benefits of consumer
      reporting. A majority of them (88.0%) thought that consumer reporting would add
      more benefits to the existing pharmacovigilance program. Similarly, 97% of the
      respondents agreed that reporting of ADRs was necessary and 87.0% respondents had
      seen ADRs among their patients. However, 57 of them (6.0%), had not been aware
      that the national program in Malaysia allowed consumers to report ADRs. A
      majority of them (97.0%) agreed that consumers needed more education regarding
      ADR reporting. Most of them (84.0%) thought that consumers could not write valid
      reports which were similar to reports which were made by healthcare professionals
      (HCPs). A majority of the respondents (68.0%) had not heard about the consumer
      reporting program in Malaysia and half of them did not believe that consumer
      reporting could overcome under-reporting, which was the main problem of the
      national pharmacovigilance program in Malaysia. CONCLUSION: The GPs and CPs were
      aware about the importance and benefits of consumer reporting. Such reporting
      will add more benefits to the existing programmes in Malaysia, although the
      barrier that we are facing now is the doubt that they hold over patients' ability
      to write valid reports which are similar to reports which are made by healthcare
      professionals (HCPs). Therefore, the consumers need to be educated more about
      their medications, on how to validate any complaints that they had about the drug
      consumption and on how to file a proper report and channel it to the 'right'
      person or bodies. Equally importantly, the media and the non-governmental
      organizations (NGOs) should play an important role in determining the success of
      consumer reporting.

PMID- 24298471
TI  - Comparative study of processing of haemorrhagic body fluids by using different
      techniques.
AB  - BACKGROUND: Haemorrhagic fluids are samples which are commonly received for
      cytological examination. The diagnostic efficacy suffers when large numbers of
      red blood cells are present in the sample. Haemorrhagic fluids are processed by a
      variety of techniques and the common goal of each technique is selection and
      concentration of an adequate number of tumour cells with intact cell
      morphologies, without losing them during processing. AIM: Present study was
      undertaken to improve the quality of haemorrhagic fluid by using three different
      haemolysing agents, namely Carnoy's Fixative (CF), saline in Normal Saline
      Rehydration Technique (NSRT) and Glacial Acetic Acid (GAA) for haemolysis and to
      find out the most effective processing technique for better cytomorphological
      assessment. MATERIAL AND METHODS: This study was carried out on 51 haemorrhagic
      fluids. Processing of haemorrhagic fluid was done by using haemolysing agents,
      namely CF, GAA and NSRT. After processing fluids with these three techniques,
      three smears were prepared from each of them, out of which one was air dried and
      two were wet fixed. Fourth type of smear made without application of haemolysing
      agent was used as control.The smears were stained with Leishman's stain and wet
      fixed smears were stained with Hematoxylin and Eosin (H and E) , and
      Papanicolou's stain (Pap) respectively. RESULTS: NSRT showed lysis of red blood
      cells (RBCs) in 72.5% of cases, followed by that of CF in 60.8% cases and that of
      GAA in only 3.9% of cases. Retention of epithelial/mesothelial cells was seen in
      70.5% cases with NSRT, followed by that of CF in 57.8% of cases and then by that
      of GAA in 50.9% of cases. Cytomorphological details were best preserved in CF in
      60.6% of cases, followed by GAA in 58.8% of cases and NSRT in 52.9% of cases.
      CONCLUSION: The most effective method for RBC lysis in smear background and cell
      retention is NSRT and cytomorphological details are best preserved with CF. But,
      considering the overall results and procedural simplicity, it was concluded that
      NSRT was a better technique for processing of haemorrhagic fluid.

PMID- 24298472
TI  - Osteoarticular tuberculosis-a three years' retrospective study.
AB  - INTRODUCTION: Extra pulmonary TB can be encountered in various organ systems,
      like lymph nodes, serous cavities, genitourinary tract, skeletal. Musculoskeletal
      TB can cause significant functional impairment. The clinical symptoms are
      variable, pain and swelling being common symptomatology. Investigations for
      suspected cases include radiological imaging, histopathological examination,
      bacteriological examination, and polymerase chain reaction. The mainstay of
      treatment is multidrug antitubercular chemotherapy. AIM: To study the cases of
      osteoarticular TB diagnosed on biopsy, to analyse the various microscopic
      patterns, results of microbiological investigations, correlate the clinical and
      radiological features and the response to ATT. Setting and Designs: A teaching
      tertiary medical institute in North India in catchment area, where prevalence of
      tuberculosis is high. A retrospective study of cases with a biopsy diagnosis of
      bone and/joint TB, retrieved from Histopathology section of Department of
      Pathology of the tertiary institute. MATERIAL AND METHODS: The study was
      retrospective and the data was collected for the preceding 3 years. The cases
      were retrieved from the records of the department of Pathology. A total of 16
      cases were diagnosed as/suspected to be tuberculosis of bones and/joints. The
      clinical information were noted from the case files. Results of laboratory
      investigations along with relevant microbiologic investigations were noted. The
      biopsy samples were processed according to protocol. Ziehl-Neelsen stain to
      detect tubercle bacilli and PAS stain to rule out fungal infection were done.
      Microscopic features were noted. RESULTS AND CONCLUSION: Sixteen cases with a
      diagnosis of bone and/joint tuberculosis were found. The average age was 23.6
      years. The most common presentation was pain and swelling. Knee joint was most
      commonly involved (7 cases) followed by spine and ankle (3 each). All the cases
      showed epithelioid granulomas which was necrotising in 11. AFB positivity was
      found only in 4 cases. ATT was started in 12 cases with a good response. It is
      important to suspect osteoarticular TB clinically and investigate accordingly. In
      resource poor setting, study of biopsy material can aid in diagnosis, further
      guiding the management.

PMID- 24298473
TI  - Efficacy of cheiloscopy in determination of sex among South indians.
AB  - INTRODUCTION: Human identification plays a vital role in any crime investigation.
      Along with the various other established methods, cheiloscopy also plays a key
      role in linking the criminal with the crime. The ability of a technique in
      differentiating the sex of a person in the field can help in screening a large
      number of suspects. This study evaluated the efficacy of cheiloscopy in
      determination of sex among South Indians. It also studied the pattern of
      dimorphism in the lips and lip prints of south Indians. MATERIAL AND METHODS: Lip
      prints from 100 medical students (50 males and 50 females) were obtained and were
      analyzed, based on Tsuchihashi and Suzuki classification, to check for
      dimorphism. Lip dimensions were studied by using standard sliding calipers for
      dimorphism. RESULTS AND DISCUSSION: The most common pattern of lip print among
      males was Type III as compared to Type I in females. The outer four portions of
      the lip showed statistically significant differences in males and females. Middle
      portion of the lip was statistically insignificant in sex determination, based on
      lip print patterns. Thickness of the lip was significantly larger in males as
      compared to that in females and this criterion could be used to establish a
      logistic regression for determination of sex of a person. CONCLUSION: Lips not
      only significantly differ among the males and females in the pattern of the lip
      print that they present, but they also differ in their size. These features can
      effectively be used to determine the sex of a person accurately.

PMID- 24298474
TI  - Perception on the Relationship between Cancer and Usage of Tobacco and Alcohol in
      Hail, Saudi Arabia.
AB  - AIM: Increasing alcohol consumption in many countries is an important cause of
      cancer worldwide. The aim of this study was to evaluate the burden of tobacco use
      and alcohol consumption and its related perception among population of Hail,
      Saudi Arabia. METHODOLOGY: A cross-sectional survey from March to April 2012
      covering 451 participants, in the city of Hail, Northern Saudi Arabia. RESULTS:
      Out of 451 respondents, 355(78.7%) were male and 96 (21.3%) were female giving a
      male to female ratio of 3.7:1. The age range of respondents was 11 - 77 years
      with a mean of 32 years. Prevalence of tobacco use and alcoholic beverages
      consumption were 30.3% and 7.5%, respectively. Most of the tobacco users and
      alcohol consumers showed positive knowledge concerning the relation between
      tobacco use and/or alcohol consumption and cancer. CONCLUSION: It is evident that
      the prevalence of tobacco consumption is rising in the Hail region. Female
      participation in tobacco and alcohol related studies in the Hail - Saudi Arabia
      represent a major obstacle since it is considered as social stigma due to
      complete prohibition by law.

PMID- 24298475
TI  - Diabetic Profile- Screening of HBA1C - A Random Community Assessment.
AB  - BACKGROUND: Diabetes mellitus is becoming the commonest non-communicable disease
      in the world. Strict control of diabetes mellitus is associated with fewer
      incidences of complications. Screening for control of diabetes is a useful
      intervention, because diabetes is a highly morbid illness with a long
      asymptomatic phase. Glycosylated Haemoglob in (HbA1C) is the ideal parameter
      which can be used to assess the diabetic control, as this parameter is not
      alterable with single day manipulations. AIMS: Our main objective was to find out
      the mean HbA1C in a random assessment. The other supplementary objectives were to
      find out the prevalence of hypertension, smoking, obesity, vascular events and
      hypoglycaemic episodes and any possible correlation with HbA1C values.
      METHODOLOGY: The selection of 100 diabetic patients who reported to the diabetic
      centre in a randomly selected day was done. They were subjected to a simple
      questionnaire with on spot HbA1c assessment. The questionnaire described the
      evidence of vascular events, risk factors, hypoglycaemic episodes, etc. RESULTS:
      A mean HbA1C value of 8.91 was found out, which was far higher than the normal
      (7.0%). The prevalences of other variables coincided with those which were seen
      in previous studies. The hypoglycaemic episodes were high, but the patients with
      such episodes had a higher mean HbA1C. This could be possible as our patients
      consumed sweet and sugar with such events and had higher mean glucose values. It
      has been suggested that physicians and patients should work synchronously to
      achieve better diabetic control. The physician should strictly enforce weight
      reduction and quitting of smoking.

PMID- 24298476
TI  - Experiences of HIV Positive Mothers From Rural South India during Intra-Natal
      Period.
AB  - CONTEXT: Tamil Nadu comes under group I high prevalence state, with less than 1%
      prevalence of HIV infection in antenatal women but above 5% prevalence in high
      risk group. One of the ways to control HIV/AIDS in India is through Prevention of
      Parent to Child Transmission (PPTCT), the success of which lies in identifying
      pregnant women with HIV infection. But due to the stigma against HIV/AIDS among
      health care providers, HIV positive patients face discrimination in the health
      sector. AIMS: To explore the difficulties faced by rural HIV positive mothers
      during the intra-natal period. METHODS: A descriptive qualitative study was
      conducted among HIV positive mothers, in Gingee block of Villupuram district,
      Tamil Nadu, India. All the mothers who tested positive between June 2006 and May
      2010 were interviewed in-depth using an interview guide. RESULTS: There were 21
      HIV positive mothers during this period, 19 of whom gave consent. Majority of the
      mothers were <30 years of age from families belonging to lower socio-economic
      class. The discriminations faced from the health staff was avoidance of physical
      examination, rude behaviour like throwing of records on the face, discriminatory
      comments, unnecessary referrals and even refusal to provide intra-partum
      services. The negative attitude of the staff made a few mothers to deliver in
      some other institution without disclosing their HIV status. CONCLUSION: Stigma
      among health care providers towards HIV positive pregnant women acts as a barrier
      for improving access to PPTCT services in India and it poses high risk to the
      mothers, babies and also the health care providers. There is a pressing need to
      improve access to quality PPTCT services especially during the intranatal period.

PMID- 24298477
TI  - A Clinical Study of Subtype-based Prevalence of Dry Eye.
AB  - INTRODUCTION: Dry Eye is a multifactorial disease of the tearfilm and the ocular
      surface which may be due to reduced tear production or excessive tear evaporation
      resulting in discomfort, visual disturbance, and tear film instability with a
      potential damage to the ocular surface. Various population-based studies have
      been done to find out the prevalence and the magnitude of the problem. Women
      Health Study reported prevalence of 7.8% after screening 36995 subjects above 49
      years by interview. The prevalence reported by Blue Mountain Study was 15.3% .The
      Beaver Dam Study and Shiphai Eye studies are other studies reporting prevalence
      of 14.5% and 33.7% respectively. McMonnies questionnaire is a widely used
      screening instrument for Dry-Eye syndromes with sensitivity reportedly varying
      between 87% and 98% and specificity between 87% and 97%. Prevalence studies use
      McMonnie's questionnaire for screening individuals for Dry Eye, whereafter tests
      like Schirmer's test, Tear Film Break Up Time test, Rose Bengal test, Lissamine
      Green test and Meibomian Gland Dysfunction test are useful for further
      evaluation. While these tests help to differentiate the subtypes of Dry Eye such
      as Lipid Anomaly Dry Eye, Aqueous Tear Deficiency and Mucin Layer Deficiency,
      however, their sensitivity and specificity has not been widely studied.
      Additionally, very few studies have reported the prevalence of the various
      subtypes of Dry Eye. AIM AND OBJECTIVES: To determine the subtype-based
      prevalence of Dry Eye, to study the specificity and sensitivity of clinical tests
      for Dry Eye and to correlate McMonnies questionnaire with Dry Eye tests results.
      MATERIAL AND METHODS: A prospective, cross-sectional, observational study, duly
      approved by the Institutional Ethics Committee, was conducted from October 2010
      to April 2012. A total of 4750 subjects above 18 yrs of age were screened by the
      McMonnies questionnaire. Respondents having a score greater than 14.5 were
      subjected to clinical Dry Eye tests. The data obtained was analyzed using chi
      square test. p value < 0.005 was considered statistically significant.The
      specificity and sensitivity of each clinical test was calculated using Schirmer's
      test as gold standard. RESULTS: The prevalence of Dry Eye was 15.4%, with a
      female preponderance (p = 0.01) and a significant increase with age above 60
      years was noted (p<0.0001). Tear Film Break Up Time was the most reliable test
      with a good sensitivity (68.85%) and specificity (78.32%). Lipid Anomaly Dry Eye
      was the most prevalent (14.48%) followed by Aqueous Tear Deficiency (13.36%) and
      Mucin Layer Deficiency (3.51%). A positive correlation between McMonnies score
      and severity of Dry Eye was seen. CONCLUSION: This study suggests that Lipid
      Layer Anomaly is the most prevalent subtype in Dry Eye. Tear Film Break Up Time
      test is the most likely test to diagnose mild Dry Eye. McMonies Questionnaire can
      be effectively used for screening of a large population. Tear Film Break Up Time
      was found to have better sensitivity as well as specificity than other tests used
      for diagnosing Dry Eye.

PMID- 24298478
TI  - Axial length, anterior chamber depth-a study in different age groups and
      refractive errors.
AB  - INTRODUCTION: Axial length and anterior chamber depth play an important role in
      refractive status of the eye in different age groups. MATERIAL AND METHODS: The
      present study has been done on 240 patients (480 eyes) who attended eye OPD of
      Department of Ophthalmology at NIMS Medical College & Hospital Jaipur, Rajasthan,
      India. The patients attending eye OPD between July 2011 to December 2012 of
      different ages groups were without significant history of any ocular disease. The
      axial length and anterior chamber depth were measured and compared. CONCLUSION:
      Hypermetropic eyes have shallow anterior chamber depth and shorter axial length
      as compared to myopic and emmtropic eyes.

PMID- 24298479
TI  - A Prospective Real World Experience of Moxonidine Use in Indian Hypertensive
      Patients-Prescription beyond Current Guidelines.
AB  - OBJECTIVE: The primary objective of this study was to assess the use of
      moxonidine, a centrally acting anti-hypertensive agent in real world practice.
      MATERIAL AND METHODS: Patients who attended out-patients clinic with diagnosis of
      hypertension were enrolled in the study. Demographics with co-morbid illnesses of
      all patients were recorded. Patient's prescriptions were recorded and anti
      hypertensive medications were also analysed. RESULTS: A total of 990 patients
      were eligible during the study period. Moxonidine was used in 4.54% of patients.
      Two groups could be identified in moxonidine users - one Group with resistant
      hypertension (30 patients, 3.03% of total, 66.66% of moxonidine users) on
      multiple drugs to control BP and another Group with intolerance to conventional,
      first line drugs (15 patients 1.51% of total, 33.33% of moxonidine users).
      Moxonidine was not used in newly diagnosed hypertension cases. Resistant
      hypertension and renal failure predicted the use of moxonidine. Majority of drug
      used was as per current guidelines. CONCLUSIONS: Our study results reflected real
      world practice of current anti-hypertensive therapy. Patients generally receive
      medications in accordance with current recommendations and guidelines. Small but
      significant proportion of patients may require use of drugs like moxonidine to
      control high BP. Guidelines need to incorporate these real world practices.

PMID- 24298480
TI  - Reactions of nepali adults to warning labels on cigarette packages: a survey with
      employee and medical students of a tertiary care medical college of Western
      region of Nepal.
AB  - BACKGROUND: For the past 30 years, there have been no changes in the text-only
      cigarette warning labels in Nepal. During this same time period, other countries
      placed large graphic warning labels on cigarette packages. The purpose of the
      current study was primarily to compare the differences in reactions to different
      types of warning labels on cigarette packages, with a specific focus on whether
      the new warning label adopted by WHO FCTC was better than the text only label
      used by Nepal. MATERIAL AND METHODS: This study was conducted in Gandaki Medical
      College Teaching Hospital (GMCTH) in 2012, in a tertiary care hospital located in
      the western region of Nepal. Eligible study participants included in this survey
      were those aged 18 years and over and those who are studying MBBS/Nursing or who
      were employees of GMCTH. 500 participants finished the survey. Participants were
      shown nine types of warning labels found on cigarette packages.They comprised one
      text only warning label used within Nepalese market and eight foreign brand
      labels. Participants were asked about the impact of the warning labels on: their
      knowledge of harm from smoking, giving cigarettes as a gift, and quitting
      smoking. RESULTS: On comparing the Nepalese warning label with other foreign
      labels with regards to providing knowledge of harm warning, impact of quitting
      smoking and giving cigarettes as a gift, the overseas labels were found to be
      more effective. Both smokers and non-smokers thought that warning labels with
      text plus graphics were substantially more of a deterrent than text-only labels.
      CONCLUSION: The findings from this study support previous research that has found
      that text-plus graphic warning labels were more salient and potentially more
      effective than text-only labels.Warning labels are one of the component of
      comprehensive tobacco control and smoking cessation efforts. Stronger warnings on
      cigarette packages need to be part of a larger Nepalese public health educational
      efforts.

PMID- 24298481
TI  - Role of common investigations in aetiological evaluation of exudative pleural
      effusions.
AB  - BACKGROUND: Pleural effusion is a common problem encountered in daily practice.
      To Establish aetiology of exudative effusions is a diagnostic challenge to
      general practitioners and even to pulmonologists especially in resource poor
      government hospitals with lack of investigations like thoracoscopy. Some recent
      studies had shown that around 2% of patients remained undiagnosed even after
      these investigations. AIMS AND OBJECTIVE: To evaluate the role of the commonly
      available investigations such as pleural fluid study, blind pleural biopsy,
      sputum examination, CT scan thorax, bronchoscopy in the aetiological evaluation
      of exudative effusions and to ascertain the proportion of cases which remain
      undiagnosed after all the above investigations. MATERIAL AND METHODS: This was a
      prospective single-centred cross-sectional study carried out at the NRS Medical
      College, Kolkata, India from February 2008 to February 2013 which included 568
      patients of exudative pleural effusions. We performed commonly available
      procedures like pleural fluid study, blind pleural biopsy, sputum examination, CT
      scan thorax, bronchoscopic procedures to the diagnosis. RESULTS: Total number of
      patients studied were 568. Tuberculosis was the most common cause (54.57%)
      followed by malignancy (28.17%), empyema (10.56%), parapneumonic effusion (5.28%)
      and others. Carcinoma of the lung was the commonest cause of malignant effusions
      and bronchoscopic biopsy was given the highest yield of histological diagnosis
      (84.6%) followed by CT guided FNAC (77.6%) and pleural fluid cytology (55%).
      Highest yield to diagnose tubercular effusion was found in lymph node FNAC
      (81.5%) followed by pleural biopsy (62%). Sputum smear for AFB was positive in
      only 27.4% cases. Bleeding followed by pneumothorax were the most common
      complications. Complications are very less (1.3% and 0.9% respectively). 2
      patients (0.34%) remained undiagnosed even after these all above said
      investigations. CONCLUSION: Above mentioned commonly available investigations can
      ascertain diagnosis in most of the cases in the aetiological evaluation of
      exudative effusions and they are relatively safe procedures.

PMID- 24298482
TI  - Clinical Profile of Patients Admitted with Swine-Origin Influenza A (H1N1) Virus
      Infection: An Experience from A Tertiary Care Hospital.
AB  - BACKGROUND: Pandemic influenza A (H1N1) 2009 has posed a serious public health
      challenge world-wide. H1N1 critical illness mostly affects young patients and is
      often fatal. OBJECTIVE: Primary objective was to study clinical profile of the
      patients admitted with confirmed H1N1 swine flu infection. Secondary objective
      was to observe the risk factors associated with complications like need of
      mechanical ventilation and or death among H1N1 infected patients. MATERIAL AND
      METHODS: A prospective observational study was conducted in a tertiary care
      teaching hospital from June 2009, to December, 2011. H1N1 infection was confirmed
      by reverse transcriptase PCR. Statistical analysis was done by SPSS, version 11.
      Binary logistic regression was used to find out independent risk factors for
      morbidity. RESULTS: Total 495 patients were tested for H1N1 infection. Among
      them, 115 (23%) were positive and 88(76%) required admission. Median age of
      cohort was 29 years and 87% of the patients were below 54 years of age. Most
      common presenting symptoms were fever (98%), followed by cough (86%) and sore
      throat (54%). Out of 88 patients, 14 (16%) required mechanical ventilation and
      6(6.8%) died. Lymphopaenia (Lymphocytes <10%) and presence of patchy infiltrates
      on chest X-ray (CXR) the time of presentation were independent risk factors
      associated with need of mechanical ventilation or death in H1N1 infected patients
      by multivariate analysis. CONCLUSION: Present study showed that H1N1 swine flu
      mainly affected people who were < 54 years of age. Majority of patients improved
      with antiviral treatment. Lymphopaenia and CXR which showed bilateral pneumonia
      at time of presentation were found to be independent risk factors associated with
      requirement of mechanical ventilation and/or death in H1N1 infection. Pregnant
      females with flu constituted 33% of total mortality. High priority should be
      given to such patients. Further community based studies are required to analyze
      the actual impact of H1N1 infection in the community.

PMID- 24298483
TI  - Trace elements in febrile seizure compared to febrile children admitted to an
      academic hospital in iran, 2011.
AB  - BACKGROUND AND AIM: Pathogenesis of Febrile Convulsion (FC) is unknown but some
      elements and genetic predispositions have been considered in the top list. This
      case-control study was designed to compare some trace elements in paediatrics who
      were admitted with FC and those in febrile ones without seizure attacks at an
      academic hospital in northeast of Iran. MATERIAL AND METHODS: This case-control
      study was done from June 2010 to July 2011 on 160 paediatrics (6-months to 5
      years old) who were diagnosed with FC and on 160 age-matched febrile children as
      control group. Data on the age, gender, past history of fever and convulsion, age
      at the first episode of seizure and family history of FC were gathered by using a
      designed checklist. Complete Blood Count (CBC), serum iron, Total Iron Binding
      Capacity (TIBC), zinc, magnesium and calcium were tested after taking informed
      consents from the parents. Serum levels of trace elements were measured by a
      photometric method. Independent t-test or non-parametric Mann-Whitney test were
      used to compare means between two groups. RESULTS: There were no significant
      differences between the cases and controls with regards to the gender or age.
      TIBC and magnesium were lower in FC, but calcium, iron and zinc were higher in FC
      as compared to those in the other group (not significant). CONCLUSIONS: So, it
      could be said that deficiency of trace elements was not significantly related to
      febrile convulsion in our study and it seemed that these tests were not necessary
      in FC cases. But further investigations on other trace elements are needed.

PMID- 24298484
TI  - A comparative study of clinical profiles of vivax and falciparum malaria in
      children at a tertiary care centre in uttarakhand.
AB  - BACKGROUND: Falciparum malaria has been constantly associated with high morbidity
      and mortality for a long time. Vivax malaria, which was once thought to be a
      relatively benign condition, is appearing in its more malignant form, with
      severity gradually becoming a serious concern. AIM: This study is aimed to find
      out and compare the clinical and pathological manifestations of vivax and
      falciparum malaria in pediatric age group in Uttarakhand. SETTING AND DESIGN: A
      prospective study was carried out at a tertiary care hospital of a medical
      college in Uttarakhand, India. MATERIAL AND METHODS: This study was done for a
      period of 2 years, from December 2010 to November 2012. Patients of 18 years age
      or below from Uttarakhand and nearby regions, who were smear positive or antigen
      positive were included in the study. STATISTICAL ANALYSIS: p value was calculated
      using Pearson Chi-square with Yates correction by DAG stat software. RESULT:
      Eighty Five patients were found to be suffering from malaria. 61 (71.8%) had
      vivax malaria, while 24 (28.2%) patients suffered from falciparum. Larger
      majority of malaria patients in both the groups happened to be males. The
      detailed study of morbidity profile clearly establishes that the complication
      related severity, earlier attributed to only falciparum is equally seen in vivax.
      Thrombocytopenia was the commonest finding in both. Other complications seen in
      both groups were those of cerebral malaria, severe anemia, ARDS, renal failure,
      malarial hepatitis, leucocytopenia, pancytopenia, shock with multiorgan
      dysfunction and hemoglobinuria. Even the mortality in the two groups was of the
      same order as p value calculated for the difference between the two species was
      well above 0.05. CONCLUSION: Vivax malaria is an important cause of mortality and
      morbidity. The severity of illness is almost similar in both vivax and falciparum
      malaria.

PMID- 24298485
TI  - Topical Phenytoin Application in Grade I and II Diabetic Foot Ulcers: A
      Prospective Study.
AB  - BACKGROUND: India is fast becoming world diabetes capital. Diabetic foot
      infections are major problems among innumerable complications associated with
      diabetes. MATERIAL AND METHODS: A randomized control study was conducted to
      evaluate the effect of topical phenytoin on healing in diabetic foot ulcers. One
      hundred patients with grade I/ II diabetic foot ulcers were randomly divided into
      two equal groups. Patients subjected to topical phenytoin dressing were
      classified under study and those who underwent normal salinewound dressings were
      classified as control. Both the groups were compared in terms of discharge,
      slough, wound area reduction and duration of hospital stay. RESULTS: Discharge
      and slough from wound reduced significantly by day 14 in phenytoin group and
      within 21 days in control group. Mean duration of hospital stay in phenytoin
      group was 20 days, whereas in control group, it was 26 days. This difference was
      statistically significant (p value <0.005,df 1). CONCLUSION: Hence, Phenytoin
      proved to be useful as a topical agent in promoting healing and in controlling
      infections in diabetic foot ulcers.

PMID- 24298486
TI  - Influence of endomeriotic cyst diameter and the severity of endometriosis on the
      ovarian parenchyma excised during laparoscopic cystectomy.
AB  - INTRODUCTION: Endometrioma is a common form of endometriosis and it is
      represented by endometriotic deposits within the ovaries which accounts for upto
      17-44% of cases. Laparoscopic stripping of ovarian endometriotic cysts is an
      accepted technique owing to low recurrence rates. Decrease in residual ovarian
      tissue volume was noted in many studies followed cystectomy. This study aims at
      estimating whether the size of endometriotic cyst is related to ovarian
      parenchyma excised along with cyst wall. MATERIAL AND METHODS: Prospective study
      was done at University teaching hospital for one year. A total of 56 women
      underwent laparoscopic endometriotic cystectomy. Cystectomy was done by stripping
      method and endometriosis was staged according to revised American Society of
      Reproductive Medicine classification (rASRM). The endometrioma wall was evaluated
      histologically and were categorised into 2 groups based on semi- quantitative
      scale of 0-4. Group 1 and 2 showed grade 0, 1, 2 and 3, 4 in the cyst wall
      respectively. RESULTS: Mean age of patients was 31.4 years, duration of
      infertility was 4.1 years and cyst diameter measured 6.3 cm. 73.2% (n=41) were in
      Group 1 and 26.8% (n=15) were in Group 2 , mean cyst diameter was being 4.3 cm
      and 5.0 cm respectively. There was no significant statistical correlation between
      preoperative cyst diameter and ovarian parenchyma removed (p=0.15). 93.3% (n=14)
      of group 2, and only 65.8% (n=27 ) of group 1 were found to have moderate to
      severe endometriosis, indicating there is correlation between disease severity
      and loss of ovarian tissue (p= 0.04). CONCLUSION: Endometriotic cystectomy when
      performed with accurate surgical technique leads to no significant ovarian tissue
      removal. However, disease severity significantly determines the loss of normal
      ovarian parenchyma.

PMID- 24298487
TI  - What type of lectures students want? - a reaction evaluation of dental students.
AB  - INTRODUCTION: An one hour didactic lecture is the common method of teaching in
      dental colleges in India. Lengthy lectures are boring and students are passive
      recipients of the information. Interactive lectures are suggested as a means of
      overcoming the disadvantages of regular lectures. AIMS: The present study was
      conducted to pilot various methods of making lectures interactive and to find the
      students' reactions to interactive lectures as compared to regular lectures.
      MATERIAL AND METHODS: An entire batch of first year dental students (n = 78) was
      exposed to both interactive and regular lectures for the cardiovascular system in
      physiology. Among the total number of 12 lectures, alternate lectures were
      conducted in an interactive style. At the end of the 12 lecture series, students'
      opinions were obtained using a structured feedback evaluation questionnaire,
      consisting of five statements, on a five point Likert scale. Statistical Analysis
      was done using SPSS software, version 15. RESULTS: Interactive lectures were
      found to be more useful than regular lectures by 92% of the students.
      Significantly more number of students agreed or strongly agreed that interactive
      lectures kept them attentive, created interest, overcame monotony, motivated them
      for self learning and provided well defined learning than regular lectures. Among
      the different techniques which were used, the students preferred use of video
      clippings (58.1%), followed by each-one-teach-one. RESULTS of the present study
      support the use of interactive lectures for ensuring increased interest and
      attention of students during lectures. CONCLUSION: Interactive lectures were more
      accepted and considered to be more useful than regular lectures by the students.

PMID- 24298488
TI  - Effect of acupressure on post-operative nausea and vomiting in cesarean section:
      a randomised controlled trial.
AB  - BACKGROUND: Because of potential side effects of chemical treatments and in order
      to decrease the risk of nausea and vomiting in post-operative patients, there is
      a necessary requirement for some alternative therapeutic methods such as
      Acupressure. AIM: The present randomized clinical trial study aimed to compare
      the effects of Acupressure and Metoclopramide on postoperative nausea and
      vomiting in Caesarean Sections. SETTING AND DESIGN: The patients who were
      subjected to caesarean surgeries, who were referred to the Ilam Mustafa Hospital
      in the west of Iran, were enrolled in this randomised clinical trial study.
      MATERIAL AND METHODS: Totally, 102 patients who were selected for elective
      Caesarean Section were included in this study. Patients were randomly assigned to
      one of three groups, with 34 cases in each group. All groups were matched for
      effective factors on nausea and vomiting in inclusion and exclusion criteria. The
      control group did not receive any intervention, the second group received 10 mg
      Metoclopramide intravenously, immediately prior to anaesthesia induction and in
      the third group, Acupressure bands were applied at the P6 points on both wrists,
      15 minutes before anaesthesia induction. Intra-operative and post-operative
      emetic episodes were recorded by a trained investigator. The patients who
      experienced nausea were evaluated on a linear numeric scale which ranged from 0
      (no) to 10 (severe). Statistics and Results: The incidence of nausea and vomiting
      in postoperative periods was lower in Metoclopramide and Acupressure groups as
      compared that in the control group. The frequency of anti-emetic which was used
      was significantly higher in control group as compared to those in the other
      groups (p<0.001). No side effects or complications were caused by any
      intervention. CONCLUSION: In parturients who underwent caesarean deliveries which
      were performed under spinal anaesthesia in this study, use of Metoclopramide and
      Acupressure was found to be equally effective for reducing emetic symptoms
      (nausea, retching, and vomiting).

PMID- 24298489
TI  - Sub-Lingual Spray Versus Pearl of TNG as A Provocative Agent for Tilt Table Test.
AB  - OBJECTIVE: The aim of this study was to determine the false positive ratio of
      Tilt Table Test (TTT) result by using TNG spray (Sub-lingual; SL) as compared to
      TNG pearl in patients referred to military service. MATERIAL AND METHODS: This
      was a prospective study. It was conducted on 110 cases referred for military
      service, expressed vasovagal symptoms. We divided the subjects into three groups;
      first Group (60 cases) used TNG pearl for provoking syncope in TTT, Group 2 (50
      cases) and Group 3 (control cases) used TNG spray in the same dose (0.4 mg).
      RESULTS: In the first step of tilt study, 10%, and 8% of subjects had fainted on
      not using provoking drug in cases and controls, respectively. After using the
      drugs, 36.6%, 96% and 18% showed positive results in pearl, spray and the control
      groups, respectively (p<0.05). CONCLUSION: Rather than pearl group, a 40 minute
      tilt using TNG spray showed significant higher positive results, which may be
      incorrectly positive. Using this form of TNG seems not useful for distinguishing
      and diagnosing vasovagal shocks, especially in subjects referred for military
      service capacity. For constant evidence, a cross-over clinical trial study is
      required, involving suspected cases divided into two groups, who both will be
      examined with spray and pearl.

PMID- 24298490
TI  - Liver stiffness measurement by fibroscan predicts the presence and size of
      esophageal varices in egyptian patients with HCV related liver cirrhosis.
AB  - BACKGROUND AND AIM: Liver stiffness measured by transient elastgraphy correlates
      with Hepatic vein pressure gradient, liver Stiffness value of 21 kpa predicts
      significant portal hypertension. Aim is to predict esophageal varices presence by
      fibroscan and possible grading by degree of liver stiffness in HCV related
      cirrhotic patients. MATERIAL AND METHODS: Thirty two HCV related cirrhotic
      patients were recruited, age > 18 years, BMI< 35, no history of: upper GI
      bleeding, hepatocellular carcinoma, abdominal collaterals, ascites. Patients
      underwent clinical examination, laboratory investigations, abdominal
      ultrasonography, upper endoscopy and fibroscan. They divided into (Group I= no
      varices, Group II =small varices (Grade 1 & 2), Group III = large varices (Grade
      3 & 4). RESULTS: Age is higher in Group III than I & II (55+6.6 vs 49.5+4.7 &
      48.9+4.7, p-value 0.04) respectively, Groups were gender & BMI matched, fibroscan
      values in Group I vs II & III were 27 Vs 49.4, p value 0.01, cutoff 29.7 Kpa
      (sensitivity 95% & specificity 67%) while its value in Group II vs III were 38.4
      vs 60.4, p value 0.002, cutoff 38.2 Kpa (sensitivity 100% & specificity77.3%).
      Platelet count, splenic size, platelet count/splenic size in Group I vs II & III
      were 107.166 vs 72.900, 13.8 vs 15.4, 803.6 vs 478, p value 0.01, 0.008, 0.005,
      cutoff 80.000, 14.5, 545, sensitivity & specificity (85%&75%, 75%&75%, 85%&84%)
      respectively. On multivariate analysis fibroscan (OR 1.113; p=0.005) & platelet
      count/splenic size (OR 0.995; p=0.012) were positive predictors of esophageal
      varices presence. CONCLUSION: Fibroscan is a good non-invasive method to predict
      esophageal varices presence & possible grading with high sensitivity.

PMID- 24298491
TI  - Role of voglibose in the treatment of prediabetes in Indian population: a cross
      speciality survey.
AB  - BACKGROUND: Prediabetes is a precursor of overt Type 2 Diabetes Mellitus (DM) and
      it is associated with insulin resistance and an increased risk for cardiovascular
      disease. ACE and AACE recommend only lifestyle modifications for the management
      of prediabetes. A recently published meta-analysis suggested that drug therapy
      was associated with a better control of diabetes. Voglibose was recently approved
      for the management of prediabetes in Japan. MATERIAL AND METHODS: A well
      structured questionnaire was sent to 117 doctors across India (52 diabetes
      specialists, 45 general practitioners, and 20 specialists from other branches of
      medicine) to understand their views on the management of prediabetes, especially
      with regards to voglibose. RESULTS AND CONCLUSION: There was an equivocal
      response to the question as to whether only diet and exercise were sufficient for
      the management of prediabetes. Most of the respondents used metformin for the
      management of prediabetes, while voglibose was the most favoured second-line
      drug. Almost all the respondents agreed that the approval which voglibose got in
      Japan for the management of prediabetes was relevant in India as well. Only 51.3%
      of all respondents had prescribed voglibose for prediabetes. Thus, voglibose
      appears to be popular second-line drug for the management of prediabetes.

PMID- 24298492
TI  - Effect of Deep Cervical Flexor Training vs. Conventional Isometric Training on
      Forward Head Posture, Pain, Neck Disability Index In Dentists Suffering from
      Chronic Neck Pain.
AB  - Neck pain accounts for 15% of all soft tissue problems seen in general practice
      and are a common reason for referral to physiotherapy treatment. The prevalence
      of neck pain in dentists is 74.3%. Musculoskeletal symptoms in dentists are
      caused due to many reasons for e.g., prolonged static posture, repetitive
      movements, suboptimal lighting, and genetic predisposition. Since deep cervical
      muscle activity is required in synergy with superficial muscle activity to
      stabilize the cervical segments, a study is needed, to compare the effectiveness
      of deep cervical flexor (DCF) training and posture correction training on neck
      pain and neck disability index and forward head posture. AIM: To determine and
      compare the effect of DCF training on forward head posture, neck pain and neck
      disability index in dentists suffering from chronic non severe neck pain.
      MATERIAL AND METHODS: Total of 30 subjects were selected, based on inclusion and
      exclusion criteria, who were further divided into Experimental and Control
      groups. Baseline information of dependent variables was taken at the beginning of
      study on day one, for Visual Analogue Scale (VAS) and Neck disability Index
      (NDI). Forward head posture was measured on day one using digital photograph
      technique. Then, Experimental group was given DCF training and Control group was
      given conventional isometrics training (CIT) for 4 weeks under supervision of
      examiner. All measurements were repeated at end of 4(th) week, on completion of
      study. RESULTS: It was observed that pain and disability had reduced in both
      groups on group analysis. But the forward head posture had improved significantly
      in experimental group only. CONCLUSION: DCF training is more effective than CIT
      in improving forward head posture, decreasing pain and disability in dentists
      suffering from chronic neck pain.

PMID- 24298493
TI  - Efficacy of rajayoga meditation on positive thinking: an index for self
      satisfaction and happiness in life.
AB  - OBJECTIVES: Psychological studies have shown that brief period of mindfulness
      meditation significantly improves critical cognitive skills. But, there are no
      studies which have assessed the effects of Brahma Kumaris Rajayoga Meditation
      (BKRM) practice on positive thinking and happiness in life. The present study was
      designed to test the hypothesis is BKRM enhances positive thinking and that
      essential to attain higher levels of self-satisfaction and happiness in life.
      MATERIAL AND METHODS: This study is a cross sectional comparative study which was
      done between Rajayoga meditators and non-meditators. This study was conducted at
      BKRM Centres at Manipal and Udupi in Karnataka, India. Fifty subjects were
      selected for this study, which included those practising BKRM in their normal
      routine life (n=25) and non-meditators (n=25) who were aged 42.95+/15.29 years.
      Self-reported Oxford happiness questionnaire (OHQ) was administered to all
      subjects and their happiness scores and status were assessed and compared. Items
      related to self-satisfaction in life were selected from the OHQ and compared
      between meditators and non-meditators. Participants completed self-reported OHQ,
      from which data of happiness status and self-satisfaction in relation to
      meditation duration and frequency were analyzed by descriptive statistics and
      test of hypothesis. RESULTS: Mean happiness scores of BKRM were significantly
      higher (p<0.001) in meditators as compared to those in non-meditators. The number
      of meditators experiencing happiness status were significantly higher (p<0.05) in
      comparison with non-meditators. Additionally, meditators scored significantly
      higher on self-satisfaction items (p<0.001) as compared to non-meditators. There
      was no correlation between age and years of meditation practice with happiness
      score and self-satisfaction score. CONCLUSION: BKRM helps in significantly
      increasing self-satisfaction and happiness in life by enhancing positive
      thinking. Irrespective of age and years of short-term or long-term meditation
      practice, enhanced positive thinking increases self-satisfaction and happiness in
      life.

PMID- 24298494
TI  - A case of bilaterally elongated styloid process differing in osseo-morphology.
AB  - In a cranium of a male cadaver styloid processes have been found to be unusually
      long with different lengths. Elongation of styloid process involvethe entire
      'Stylohyoid complex/chain', though not rare as reported in earlier literatures,
      but the osseomorphological and radiological analysis of present case brings out a
      unique variety as its described in the article. 

PMID- 24298495
TI  - Co-Infection: Weil's Syndrome with Hepatitis B Infection- A Diagnostic and
      Therapeutic Hitch.
AB  - Undifferentiated Acute Febrile Illness (AFI) is a common clinical syndrome among
      patients seeking hospital care. Detection of co-infections at the time of
      presentation is a diagnostic challenge, especially with limited laboratory
      support. Even if detected, early treatment and cure of these co-infections can be
      difficult for the clinicians. We are presenting a rare case of Hepatitis B and
      leptospirosis co-infection with high titres of Salmonella paratyphi A and scrub
      typhus. There are a few reports of leptospirosis in Hepatitis -B infected
      individuals but no generalization can be made due to limited data. Prompt and
      accurate serological diagnosis of multiple infectious agents have becomes
      mandatory in a healthcare set-up. 

PMID- 24298496
TI  - Fonsecaea pedrosoi: a rare etiology in fungal keratitis.
AB  - Fungal corneal ulcer is common in India due to tropical climate and a large
      agrarian population that is at risk. Fonsecaea pedrosoi is the most common agent
      of chromoblastomycosis, a chronic localized fungal infection of the skin and
      subcutaneous tissues mainly involving lower extremities. We report a rare case of
      corneal chromoblastomycosis caused by F.pedrosoi, which was successfully treated
      with topical Amphotericin B followed by a long course of oral antifungal therapy.
      To the best of our knowledge, this is the first case of mycotic keratitis caused
      by F.pedrosoi, from the foothills of Himalayas. 

PMID- 24298497
TI  - Meningitis Due to Cryptococcus gattii in an Immunocompetent Patient.
AB  - The incidence of cryptococcal infection is high in developing countries such as
      India. Cryptococcus gattii, formerly known as Cryptococcus neoformans var gattii,
      is an encapsulated yeast that causes disease in both immunocompetent and
      immunosupressed individuals. The organism enters via respiratory tract and causes
      a spectrum of illness ranging from asymptomatic infection to severe illness,
      including pneumonia and disseminated infection involving multiple sites,
      including the central nervous system, eyes and skin. Cryptococcal meningitis is
      generally considered as rare in immunocompetent patients; therefore, specific
      treatment is not implemented until the organism is identified or a cryptococcal
      antigen is detected. We describe the case of a 30-years-old man without prior
      medical history who presented with meningitis and was treated successfully. This
      case illustrates the importance of considering infectious causes such as C.gattii
      in the differential diagnosis of meningitis, regardless of the patient's immune
      status. 

PMID- 24298498
TI  - Systemic mastocytosis: predominantly involving the bone, a case report.
AB  - Systemic mastocytosis (SM) is a rare clonal disorder of mast cells that can range
      from chronic smouldering type to aggressive mast cell leukaemia. It presents with
      non-specific symptoms like urticaria pigmentosa, unexplained flushing,
      hypotension and abdominal cramps, which may lead to a misdiagnosis, if there is
      no high index of clinical suspicion. This is a case report of a 52-year-old lady,
      with systemic mastocytosis, who presented with severe chronic back ache and no
      other clinical features. X - ray revealed lytic lesions in the lumbar vertebrae
      and bone marrow aspiration and a trephine biopsy examination showed infiltration
      by mast cells, with a positivity for Toluidine blue stain and CD 117. She was
      also noted to have peripheral eosinophilia, which is frequently encountered with
      this condition. She was diagnosed to have chronic indolent systemic mastocytosis
      which involved the bone predominantly. 

PMID- 24298499
TI  - Painful late recurrence of dermatofibrosarcoma protuberans of breast in a
      centurian female.
AB  - Dermatofibrosarcoma protuberans (DFSP) of the breast is rare. Late and painful
      local recurrence of this entity on this site is even more uncommon. We describe
      such a case in a 102-year-old woman, who at the age of 77 years had been operated
      for a breast lump for which only a cytopathological diagnosis of fibrohistiocytic
      tumour was available. Twenty years later, she noticed a small mass in her right
      breast over the postsurgical scar area, which gradually increased in size over
      the last five years. She presented to the surgical out-patient clinic with pain
      and redness over the swelling. Wide local excision of the tumor with generous
      tissue margin was performed under intercostal block on account of her age and
      suboptimal cardiac status. The microscopic and immunohistochemical findings
      established the diagnosis of recurrent DFSP. We report an exceptionally rare case
      of local recurrence of DFSP in the female breast and discuss in detail the
      diagnostic and therapeutic implications of this pathology. 

PMID- 24298500
TI  - Rippled pattern extraocular sebaceous carcinoma: a rare case report with brief
      review of literature.
AB  - Sebaceous carcinoma (SC) is a highly aggressive malignant adnexal tumor of
      sebaceous gland origin, accounting for less than 1% of cutaneous. Extraocular
      sebaceous carcinomas are more aggressive than their ocular counterpart with a
      predilection for the skin of head and neck, trunk, salivary glands and
      extremities in decreasing order of frequency. Rippled effect literally means
      "gradually spreading effect". In histopathology it describes the unique
      arrangement of tumor cells in palisading pattern. The tumors in which rippled
      effect has been reported include adnexal tumors like trichoblastoma,
      trichomatricoma, trichoblastoma with sebaceous differentiation, trichoblastoma
      with apocrine differentiation, sebaceoma, basal cell carcinoma, fibrohistiocytic
      tumors, mesenchymal tumors and melanocytic tumors. We report the first case of
      extra ocular sebaceous carcinoma with rippled effect with emphasis on the fact
      that differentiation from other tumors demonstrating rippled effect is important
      in view of different treatment protocols. 

PMID- 24298501
TI  - Eosinophilic cystitis mimicking bladder tumour - a rare case report.
AB  - A 16-year-old male presented with urinary urgency, a frequency of 4 months
      duration and intermittent gross haematuria which were there since one month.
      Eosinophilia was noted in complete blood count and CT KUB with contrast showed a
      filling defect in the right lateral wall, over the vesicoureteric junction.
      Cystoscopy revealed a sessile mass lesion over right vesico-ureteric junction,
      with bullous oedema . Rest of the mucosa was normal. Transurethral resection of
      lesion was performed and histological examination showed features of eosinophilic
      cystitis. Patient was treated with corticosteroids, antimicrobial agents and
      antihistaminics and he is recovering well. We are presenting this case for its
      rare presentation and its possibility of mimicking a bladder tumour. Biopsy of
      the lesion was diagnostic and an early treatment showed good results. 

PMID- 24298502
TI  - Benign mass in tonsil- cavernous hemangioma.
AB  - Cavernous hemangioma is also called as 'ANGIOMA CAVERNOSUM' or 'CAVERNOMA' as
      benign lesion of blood vessels. They are similar to strawberry hemangioma but
      deeply situated. Although most often associated with skin it is also sometimes
      found in mucous membrane, brain and the viscera. The diagnosis of hemangiomas is
      mainly based on clinical evaluation . Isolated hemangiomas in the tonsillar
      tissue is a rare occurance. In this we report had a case of adult tonsillar
      hemangioma of left side associated with recurrent tonsillitis . He was
      effectively managed surgically without any complications. 

PMID- 24298503
TI  - Peripheral arterial disease and digital gangrene: a rare presentation of diabetic
      hand syndrome.
AB  - Digital gangrene in upper limbs may be due to systemic sclerosis, trauma,
      connective tissue disorders, vasculitic disorders and various myeloproliferative
      disorders or as a part of tropical diabetes hand syndrome which follows trauma.
      Peripheral arterial disease in diabetics commonly involves lower limbs. The
      present case, 45-year-old diabetic, presented with dry gangrene in fingertips of
      both hands for last two weeks without any history of trauma or lower limb
      gangrene. On examination and workup of the patient was found to have bilateral
      upper limb arterio-occlusive disease involving ulnar vessels as a macrovascular
      complication of diabetes mellitus. This presentation of diabetic hand syndrome is
      very, very rare, hence being reported. 

PMID- 24298504
TI  - Pseudohypoparathyroidism, rare cause of hypocalcaemia!
AB  - Pseudohypoparathyroidism is a rare disorder which is characterized by end organ
      parathormone resistance, which causes hypocalcaemia, hyperphosphataemia and high
      parathormone levels. We are reporting here case of a young male who had symptoms
      of chronic hypocalcaemia, with a positive Trousseau's and Chvostek's sign on
      examination, without any features of Albright's hereditary osteodystrophy. Lab
      investigations revealed low calcium, high phosphate and high PTH levels. The
      patient was diagnosed as having Pseudohypoparathyroidism and he was treated
      successfully with Calcium and Vitamin D supplements. 

PMID- 24298505
TI  - Acute kidney injury in a patient with membranous nephropathy - a case report.
AB  - Acute Kidney Injury (AKI) is one of the most challenging problems faced by
      clinicians in the tropics owing to its fast-changing burden. Acute Kidney Injury
      is an important complication of membranous nephropathy. Causes are varied and
      include hypovolumia, crescentic conversion of preexisting nephropathy, renal vein
      thrombosis, NSAID'S, vasculitis, and sepsis. In this case report we discuss the
      case of membranous nephropathy in a young adult complicated by AKI. This report
      highlights the importance of early renal biopsy in patients with post GE AKI not
      improving on hemodialysis. Here we also discuss the potential differentials to be
      considered in a case of membranous nephropathy with AKI. 

PMID- 24298506
TI  - Paraplegic neurodeficit management post endovascular graft: a rare case of aortic
      dissection.
AB  - Acute aortic dissection is a catastrophic episode that usually presents as a
      sudden, painful, ripping sensation in the chest or back. It is associated with
      neurologic sequelae in as many as one-third of patients. We report a case of
      aortic dissection, presenting as acute paraplegia. A 50-year-old patient
      presented to us with chief complaints of paraplegia and back pain. On
      examination, strength was 5/5 in both upper extremities and 0/5 in both lower
      extremities. Deep tendon reflexes were absent in her legs. CT angiogram of aorta
      Aortic Dissection Stanford type B / De-Bakey type -III. Patient was treated with
      endovascular graft for aortic dissection, paraplegia recovered completely. 

PMID- 24298507
TI  - Occupationally related outbreak of chickenpox in hospital staff: a learning
      experience.
AB  - Varicella (chicken pox) is a highly contagious disease which is caused by
      Varicella Zoster Virus (VZV), a ubiquitous human alpha herpes virus. Nosocomial
      varicella in hospital employees can be costly to the hospital and disruptive to
      patient care. This case report describes an occupationally related outbreak of
      chickenpox in hospital staff and the lessons which were learnt by the hospital
      during this experience. 

PMID- 24298508
TI  - Unusual presentation of intussusception of the small bowel with peutz jeghers
      syndrome: report of a case.
AB  - The Peutz Jeghers syndrome (PJS) is an autosomal dominant disorder which is
      characterised by hamartomatous polyposes of the gastrointestinal tract, melanin
      pigmentation of the skin and mucous membranes, and an increased risk for cancer.
      We are reporting a case of a 15-year-old male with Peutz Jeghers syndrome, who
      presented to us with features of chronic intestinal obstruction and anaemia.
      Initially, patient was managed conservatively, but later on, an elective
      exploratory laparotomy was done for definitive management of intussusception.
      Laparotomy revealed a jejuno-jejunal intussusception with spontaneous
      recanalisation of gut which contained a long segment of gangrenous small bowel in
      the lumen. Resection and anastomosis of the jejunal segment was done. To the best
      of our knowledge, this might be the first case report on spontaneous
      recanalisation of small intestine. 

PMID- 24298509
TI  - Phytobezoar: a rare cause of small bowel obstruction.
AB  - Phytobezoar is an unusual cause of small bowel obstruction. It accounts for about
      0.4%-4% of all mechanical bowel obstruction. However, the symptoms are not very
      different from those caused by usual aetiologies of small bowel obstruction. The
      commonest site of obstruction is terminal ileum. Treatment of small bowel
      obstruction due to Phytobezoar is surgery. Prevention includes avoidance of high
      fibre diet, prokinetics particularly in patients who have undergone gastric
      surgery. A 57-year-old male presented with symptoms and signs of small bowel
      obstruction. On exploratory laparotomy Phytobezoar in the ileum was found to be
      the cause of obstruction. Diagnosis was confirmed by histopathology. 

PMID- 24298510
TI  - Left-sided Gastroschisis: A Rare Congenital Anomaly.
AB  - In gastroschisis, the defect in the abdominal wall is located almost always to
      the right of the umbilicus. Left-sided gastroschisis is a very rare entity. A
      case of left sided gastroschisis has been described here, with review of
      literature. 

PMID- 24298511
TI  - Prompt diagnosis and treatment of uterine arcuate artery pseudoaneurysm: a case
      report and review of literature.
AB  - Post-partum haemorrhage is a major determinant of maternal mortality.
      Traditionally, cases of post-partum haemorrhage caused by arterial injuries were
      managed by caesarean hysterectomies or bilateral internal iliac artery ligations.
      The diagnosis of aneurysms or arteriovenous malformations of uterine artery are
      often missed. Uterine curettage, caesarean section or vaginal delivery can result
      in uterine vascular anomalies like pseudo aneurysms, arteriovenous malformations,
      arteriovenous fistula and rupture of uterine vessels. Colour Doppler ultrasound
      pelvis allows detection of these vascular abnormalities. It helps in
      differentiating the vascular abnormalities that require embolization from non
      vascular abnormalities which can be managed by uterine curretage. Vessel
      malformations can be treated safely with transcatheter uterine artery
      embolization, but they can develop disastrous consequences with inadvertent
      uterine curettage. Transcatheter uterine artery embolization after pelvic
      angiography is the treatment of choice for uterine artery malformations and it
      has the advantage of preserving the reproductive capacity. We recommend a routine
      use of colour Doppler ultrasound pelvis for evaluation of abnormal uterine
      bleeding. 

PMID- 24298512
TI  - Delayed menopause due to ovarian granulosa cell tumour.
AB  - A patient presented to us with complaints of inability to attain menopause even
      at the age of 64. She has been having irregular cycles of bleeding for 5 days
      every 2-3 months from the age of 54. On evaluation, she was found to have
      endometrial hyperplasia and ultrasonography showed a homogenous solid ovarian
      mass of size of the 4 cm x 3.5 cm. She underwent staging laparotomy with total
      abdominal hysterectomy bilateral salpingo-oophorectomy and infra colic
      omentectomy. Histopathology confirmed granulosa cell tumour of the ovary. Most
      commonly granulosa cell tumour presented with post-menopausal bleeding and
      abnormal uterine bleeding, however, women with delayed menopause also have to be
      evaluated thoroughly for estrogen secreting ovarian tumours. There should be an
      element of suspicion if patient doesn't attain menopause as specified and they
      need to be evaluated in detail. 

PMID- 24298513
TI  - Negative pressure pulmonary oedema: a rare case report of two brothers.
AB  - Negative Pressure Pulmonary O/Edema (NPPE) is potentially life-threatening and it
      is a general anaesthesia side effect. We are mentioning a rare case report of two
      brothers who were referred to our hospital for elective surgeries (varicocele and
      septoplasty) in a 3 years period. Both of them were athletes and their
      coagulation factors were disturbed after surgeries. Pulmonary oedema was healed
      after treating it by reintubation, mechanical ventilation by Positive End
      Expiratory Pressure (PEEP), diuretics, morphine, Fresh Frozen Plasma (FFP) and
      liquid bounding. 

PMID- 24298514
TI  - Perioperative Respiratory Compromise in Patients Undergoing PCNL-A Case Series.
AB  - Percutaneous Nephrolithotomy (PCNL) is a surgical procedure which is used to
      extract renal pelvic stones. An optimum access tract, without traumatizing the
      surrounding structures, is essential for the surgery. Trauma to the surrounding
      structures and extra-vasation of the irrigating fluid may result in complications
      like hydrothorax, pneumothorax, hydro pneumothorax etc. These complications may
      produce intra- operative respiratory compromise leading on to arterial hypoxemia
      and its sequelae. A series of three case reports with review is presented here.
      First case is accumulation of irrigating fluid in the pleura causing hydrothorax
      and oxygen desaturation. Second case is extra-vasation of fluid in the abdominal
      wall and the patient was ventilated artificially for 24 hours. Third patient
      developed pneumothorax and he needed chest drainage.PCNL is done under general
      anaesthesia in prone position. The anaesthesiologist should be vigil enough to
      identify the situation and take appropriate measures to correct it. 

PMID- 24298515
TI  - Cutaneous larva migrans masquerading as tinea corporis: a case report.
AB  - A 25-year-old male was seen with complaints of itchy skin lesions over left
      thigh. On examination multiple annular scaly plaques with wavy borders,
      peripheral papules and central clearing was seen. Closer examination revealed
      multiple forked tracts with excoriated papules. A diagnosis of cutaneous larva
      migrans was made and the patient treated using T.Albendazole 400 mg twice daily
      for 7 days which resulted in complete clinical cure. 

PMID- 24298516
TI  - Acute-Onset of Multiple Painful Nodules over Forearms and Back.
AB  - Angiolipomas are benign encapsulated, well circumscribed tumours, which show
      excessive degree of vascular proliferation. Clinically, lesions present as sudden
      onset of multiple painful nodules. Pain usually does not respond to analgesics.
      We herein, report a case of a young male, presenting with multiple painful
      nodules over the forearm and back, which on histopathological examination
      revealed, encapsulated benign tumour, comprising of proliferated small-caliber
      vascular channels with microthrombi and variable amounts of mature adipose
      tissue. Pain subsided on treatment with intralesional steroids and the nodules
      were excised through a narrow-hole extrusion technique. 

PMID- 24298517
TI  - Hypereosinophilia-an unusual cause of multiple embolic strokes and multi-organ
      dysfunction.
AB  - 'Eosinophilia' can occur due to a large number of allergic, infectious,
      neoplastic, and idiopathic diseases. It can range in severity from a self
      limiting condition to a life-threatening disorder. The term 'hypereosinophilia'
      refers to eosinophil levels >1500/MUL, and regardless of the underlying cause can
      be associated with tissue and organ damage. 'Hypereosinophilic syndrome (HES)' is
      a rare disorder with sustained eosinophilia and multi-organ dysfunction in the
      absence of a discernable secondary cause. 'Undefined Hypereosinophilic Syndrome'
      is the most common type of primary hypereosinophilic diseases and we are
      reporting here one such case who presented with acute multiple embolic strokes
      secondary to biventricular apical thrombi and multi-organ dysfunction of a
      fulminant nature. This case highlights the limitation in current diagnostic
      criteria for HES and emphasizes the need for early intervention. 

PMID- 24298518
TI  - An anatomical variation in the formation of the inferior root of ansa cervicalis.
AB  - During regular dissections, we observed an unusual organization of the inferior
      root of Ansa Cervicalis (AC). The superior root of ansa arose normally from the
      hypoglossal nerve. The ventral ramus of the C2 spinal nerve divided into two
      branches. One of its branches joined the superior root independently to form a
      loop at a higher level. Another branch ran along the vagus nerve, joined with the
      ventral ramus of C3 spinal nerve, finally connected with the superior root and
      formed the second loop at a lower level. No variation was found in formation of
      superior root. Knowledge on the possible deviations in the formation of these
      roots is clinically important, to prevent iatrogenic injuries in surgical
      procedures such as thyroplasties, arytenoids adductions, and Teflon injections. 

PMID- 24298519
TI  - Human gall-bladder communicating with skin: rare anatomical swerve.
AB  - Cholecysto-cutaneous fistula is an extremely rare phenomenon in present era. We
      report a case of this rare entity wherein patient presented with unique history
      of passage of stones per umbilicus. Newer radiological investigations
      specifically CT fistulography help in surgical planning by not only delineating
      external fistulas but only diagnosing any internal fistula. 

PMID- 24298520
TI  - Myofibroblastoma breast with unusual morphological features. Cytohistopathogical
      diagnostic pitfalls and role of immunohistochemistry-review of literature.
AB  - Myofibroblastoma (MFB) is a rare mesenchymal tumour, derived from mammary stromal
      fibro-myofibroblasts, with diverse biological and morphological behaviour. Large
      and cellular myofibroblastomas, especially those with epitheliod like cells, can
      mimic various spindle cell lesions and metaplastic carcinomas, thus posing
      diagnostic challenge. A 50-year woman presented with slow growing, painless lump
      in the left breast. Fine Needle Aspiration (FNA) smears showed predominant
      atypical spindle cell population, pleomorphic epithelial like cells and giant
      cells. Cytodiagnosis of atypical spindle cell lesion with the possibility of
      metaplastic carcinoma was suggested. Histopathological examination showed
      fascicles of spindle cell population admixed with epithelial like cells, atypical
      cells and tumour giant cells, thus raising differential diagnosis of metaplastic
      carcinoma, low grade spindle cell sarcoma and myofibroblastic tumour. Lymph nodes
      were negative for metastatic deposits. Immunohistochemistry revealed variable
      coexpression of markers for vimentin, fibronectin, CD34, SMA (smooth muscle
      actin), but negative expression for , S-100, CD99, CK7 (cytokeratin 7), HMWK
      (high molecular weight keratin), ER (oestrogen receptor) and PR(progesterone
      receptors). Diagnosis of cellular myofibroblastoma with mixed unusual
      morphological features was defined, based on both histological and
      immunohistochemical features. MFB may cause a potential diagnostic pitfall while
      interpreting FNA and histopathological sections due to its wide differential
      diagnosis. The distinction of MFB from its cytohistological mimics of malignancy
      is crucial to avoid unnecessary extensive procedures. The case report emphasizes
      the role of immunohistochemistry as gold standard in diagnosis of MFB. The case
      is also being presented because of its large size and rare mixed unusual
      morphological features. 

PMID- 24298521
TI  - Prevalence and Incidence of Gemination and Fusion in Maxillary Lateral Incisors
      in Odisha population and Related Case Report.
AB  - AIM: A survey was conducted to analyze the prevalence and incidence of dental
      anomalies in relation to maxillary lateral incisors in the Odisha population. A
      multidisciplinary approach for aesthetic management of a geminated tooth is
      described. MATERIAL AND METHODS: A total of 1062 subject, aged between 15-30
      years (724 males and 338 Females) were randomly screened at Institute of Dental
      Sciences, Bhubaneswar, Odisha India. Each subject was examined clinically and
      radiovisuographically for dental anomalies in relation to maxillary lateral
      incisors. In the related case described, endodontic management and aesthetic
      correction of geminated maxillary lateral incisors was done. RESULTS: Five dental
      anomalies i.e. gemination, fusion, missing lateral incisors (both unilateral and
      bilateral), peg shaped incisors (unilateral and bilateral), and dens in dente
      were observed. Anomalies found were Peg shaped; 2.82%, Missing;1.88%,
      Gemination;0.28%, Fusion;0.18% and Dens in Dente;0.18%. CONCLUSION: Comparison of
      these results with that of other studies indicated that anomalies in lateral
      incisors occur at different frequencies among various countries and communities
      in the world. In the case since maxillary lateral incisors are in the aesthetic
      zone, recognizing these anomalies will facilitate a successful treatment.

PMID- 24298522
TI  - Clinical effects of subgingivally delivered spirulina gel in chronic
      periodontitis cases: a placebo controlled clinical trial.
AB  - AIMS AND OBJECTIVES: The aim of this study was to assess the clinical effects of
      Spirulina in-situ gel as an adjunct to Scaling And Root Planning (SRP) in the
      treatment of chronic periodontitis subjects. MATERIAL AND METHODS: 64 sites were
      selected with probing pocket depth of >=5mm and they were divided into 2 groups;
      33 sites were treated with SRP along with spirulina gel (Group A) and 31 sites
      were treated with SRP alone (Group B). Clinical parameters were recorded at
      baseline before SRP and at 120(th) day after the treatment therapy. The
      parameters included Probing Pocket Depth (PPD) and Clinical Attachment Level
      (CAL). RESULTS: Both the groups showed significant improvement in the parameters.
      However, Group A (SRP along with spirulina) showed statistically significant
      decrease in mean probing pocket depth and gain in the clinical attachment level
      after 120 days as compared to Group B SRP alone. CONCLUSION: Locally delivered
      spirulina gel, along with scaling and root planning, has been shown to cause a
      beneficial impact. The efficacy of the product as a local drug delivery system in
      the non-surgical treatment of periodontitis without any side effects has been
      proved. Spirulina appears to be promising. It exerts strong anti-inflammatory
      effects which are closely connected with its antioxidative activity. This study
      can have a significant impact on the treatment procedures of periodontitis, with
      the use of blue green algae in the future.

PMID- 24298523
TI  - Rheumatoid Arthritis among Periodontitis Patients in Baddi Industrial Estate of
      Himachal Pradesh, India: A Cross Sectional Study.
AB  - AIM: To determine whether there is a relationship between periodontal disease and
      rheumatoid arthritis. METHODS: A total of 1520 (852 - periodontal group; 668 -
      general group) individuals of 30-70 years age group and residents of Baddi
      industrial estate in Himachal Pradesh, India, were assessed for the prevalence of
      rheumatoid arthritis and Periodontal Disease (PD). The prevalence and severity of
      periodontitis were determined by recording the Community Periodontal Index (CPI)
      with loss of attachment, based on WHO guidelines (1997). The criteria considered
      for diagnosis of rheumatoid arthritis were as those given by American Rheumatism
      Association -1988. Frequency distributions for bivariate analysis and logistic
      regression for multivariate analysis were used for assessment of statistical
      association between variables. RESULTS: In patients referred for periodontal
      treatment, the prevalence of rheumatoid arthritis was 4.4%. Females (3.2%) and
      subjects aged above 50 years (3.5%) showed a significantly higher prevalence in
      comparison to their counterparts (p<0.001). The odds of rheumatoid arthritis in
      females were nearly three times (OR=2.813) higher than those in males, which was
      also statistically significant (p<0.05). CONCLUSION: The findings provide
      evidence of a relationship, suggesting that individuals with moderate to severe
      periodontal disease are at higher risk of suffering from rheumatoid arthritis and
      vice versa.

PMID- 24298524
TI  - Doxycycline poly e-caprolactone nanofibers in patients with chronic periodontitis
      - a clinical evaluation.
AB  - AIM: To develop a low-dose controlled-release delivery system for the treatment
      of periodontal infections. A new sustained release drug system of Poly e
      caprolactone (PCL) nanofibers containing doxycycline (DOX) was successfully
      electrospun and evaluated clinically for periodontal diseases. The retentive
      doxycycline nanofibres were shown to provide a controlled delivery of the drug.
      MATERIAL AND METHODS: Nanofibers were prepared with DOX in PCL by electrospinning
      technique. The drug-coated nanofibres provided sustained effect up to a period of
      11 days (264 h) and followed first order release. Forty sites in 7 patients (4
      females and 3 males) with chronic periodontitis (5-8mm probing depth) were
      allocated in 2 experimental treatment groups, Group A-SRP (Scaling and Root
      Planing) + DOX nanofibers and Group B -SRP (Scaling and Root Planing) alone
      (control group). All these patients were evaluated clinically for probing depth
      (PD), plaque index (PI) and gingival index (GI). RESULTS: Both the treatment
      groups were found to be efficacious in the treatment of periodontal disease as
      demonstrated by improvement in PD, PI and GI. CONCLUSION: Combination of SRP
      (Scaling and Root Planing) + DOX nanofibers (Group A) resulted in added benefits
      compared to the control group.

PMID- 24298525
TI  - A Comparative Evaluation of the Effect of Bonding Agent on the Tensile Bond
      Strength of Two Pit and Fissure Sealants Using Invasive and Non-invasive
      Techniques: An in-vitro Study.
AB  - BACKGROUND: Newer technologies and the development of pit and fissure sealants
      have shifted the treatment philosophy from 'drill and fill' to that of 'seal and
      heal'. AIMS: The purpose of this in-vitro study was to evaluate the effects of
      bonding agents on the tensile bond strengths of two pit and fissure sealants by
      using invasive and non-invasive techniques. STUDY DESIGN AND METHODS: One hundred
      and twenty bicuspids were collected and teeth were divided into two groups: Group
      I (Clinpro) and Group-II (Conseal f) with 60 teeth in each group. For evaluating
      tensile bond strengths, occlusal surfaces of all the teeth were flattened by
      reducing buccal and lingual cusps without disturbing fissures. Standardised
      polyvinyl tube was bonded to occlusal surfaces with respective materials.
      Sealants were applied, with or without bonding agents, in increments and they
      were light cured. Tensile bond strengths were determined by using Universal
      Testing Machine. STATISTICAL ANALYSIS: Data were then statistically analysed by
      using Student t-test for comparison. RESULTS: A statistically significant
      difference was found in tensile bond strength in invasive with bonding agent
      group than in non-invasive with bonding agent group. CONCLUSION: This study
      revealed that invasive techniques increase the tensile bond strengths of sealants
      as compared to non- invasive techniques and that the use of a bonding agent as an
      intermediate layer between the tooth and fissure sealant is beneficial for
      increasing the bond strength.

PMID- 24298526
TI  - Establishing an Association between Renal Failure and Periodontal Health: A Cross
      Sectional Study.
AB  - Periodontal infections can act as focus of infection, aggravating the
      immunocompromised state of End Stage Renal Disease patients (ESRD). AIM:
      Evaluation of the periodontal health status of ESRD patients undergoing
      haemodialysis and establishing the underlying association between renal failure
      and periodontal disease. MATERIAL AND METHODS: Eighty control and test subjects
      were included in the study, after matching age and sex. Creatinine and GFR were
      measured in each patient. Oral hygiene index- Simplified (OHI-S), Gingival Index
      (GI), Pocket Depth (PD) and Clinical Attachment Level (CAL) were recorded as
      periodontal parameters to assess the correlation between the subjects of the two
      groups. Further, the test group was divided into three sub-groups, on basis of
      duration, as less than 6 months, from 6 months to one year and more than one
      year. STATISTICAL ANALYSIS: Student's t - test and ANOVA were used to analyze the
      inter-group and intragroup comparisons. RESULTS: Statistical significant
      difference was observed for all periodontal parameters between the test and
      control group. However, difference amongst periodontal parameters on basis of
      duration of haemodialysis was seen between the subgroups of test subjects, it was
      not found to be statistically significant. CONCLUSION: Severity of periodontal
      diseases in ESRD patients undergoing haemodialysis majorly affected due to
      debilitating condition of the subjects. Dialysis vintage has only a small role to
      play in worsening of the condition. Further research is needed to potentiate the
      establishment of two-way relationship between renal disease and periodontal
      condition.

PMID- 24298527
TI  - Bone scintigraphy and panoramic radiography in deciding the extent of bone
      resection in benign jaw lesions.
AB  - OBJECTIVE: To find out the value of correlating radiographic and scintigraphic
      imaging for defining the extent and nature of benign jaw lesions (BJL). MATERIAL
      AND METHODS: Twenty patients with histologically proven benign lesions of the
      jaws were investigated pre-operatively by panoramic radiography (PR) and bone
      scintigraphy (BS). To test the efficacy of combination of these two imaging
      modalities, their results were compared with intra-operative and
      histopathological findings. RESULT: Most of the benign lesions presented
      radiographically as well-defined bone destructions with fine sclerotic rims. Such
      lesions were found to be silent on scintigraphs and the extent of radionuclide
      uptake was same as radiographically visible extent of bone involvement. However,
      aggressive lesions showed ill-defined bone destructions without sclerotic rims on
      radiographs and their scintigraphic uptake correctly exceeded the radiographic
      extent of the bone involvement. CONCLUSION: The efficacy of combination of both
      complementary imagings is rewarding in defining the extent of the BJL, especially
      when radiographic margins are not so well defined. So, that surgical excisions
      will be complete and the possibility recurrences is reduced.

PMID- 24298528
TI  - Characteristics of palatal rugae patterns in west godavari population of India.
AB  - Palatal rugae refer to the ridges on the anterior part of the palatal mucosa,
      each side of the median palatal raphe and behind the incisive papilla. Various
      studies on different populations have reported unique rugal patterns within each
      population. AIM: To study, analyse and report the significant palatal rugae
      patterns among West Godavari District population and compare with the patterns
      reported in the literature, which can aid as an additional method of
      identification in cases of crime or mass disasters. MATERIAL AND METHODS: Pre
      orthodontic casts of 100 samples (50 males and 50 females) were selected. The
      method of identification of the rugae pattern used was that of Thomas et al
      (1983) which includes the number, shape and unification patterns of rugae. The
      different types of rugae between males and females were statistically analyzed
      and compared with other population studies in the literature. RESULTS: A
      statistically insignificant (p>0.05) higher mean primary rugae scores was found
      in males (7.48+/-2.45) while secondary (3.38+/-2.02) and tertiary (2.56+/-1.84)
      rugae were more among females. Both genders showed predominance in wavy (males =
      4.82+/-1.91 and females = 4.74+/-1.98) type of distribution.Commonly observed
      pattern in the mode of unification was converging (58%) in males and diverging
      pattern (62%) among femaleswhich was statistically significant (p=0.04).
      CONCLUSION: The findings showed a specific rugae pattern in this group when
      compared to other populations reported in the literature. Palatal rugae patterns
      are definitely associated with regional variation and can aid as an additional
      tool in forensic identification procedures.

PMID- 24298529
TI  - An Evaluation of the Adherence of Candida albicans on the Surface of Heat Cure
      Denture Base Material Subjected to Different Stages of Polishing.
AB  - BACKGROUND: Candidiasis is common in denture wearers. Rough surfaces of dentures
      promote denture plaque formation and maturation, thus justifying the need for
      smooth surfaces. Proper finishing and polishing of dentures provide smooth
      surfaces. Thus, this study was done to assess the adherence of Candida to heat
      polymerized acrylic resin surfaces which were subjected to different stipulated
      polishing methods. MATERIAL AND METHODS: A total of 48 acrylic resin specimens of
      dimension 10x10x3 mm(3) were fabricated and divided into four groups, A, B,C and
      D, with 12 specimens in each group, according to method of polishing step which
      was employed. Subsequently, they were subjected to an adherence assay. All the
      data was statistically analyzed by using One-way ANOVA and differences within the
      groups were analyzed by using independent sample t-test. RESULTS: RESULTS
      revealed that group A which was unpolished had a mean adherence of 2.92 and it
      was finished by using sand papers. Group B had a mean adherence of 0.5 and it was
      finished by using sand papers, followed by polishing with pumice. Group C had a
      mean adherence of 2.92 and finishing was done by using sandpaper which was
      followed by polishing with the use of pumice and rouge. Group D had a mean
      adherence of 37.1667. CONCLUSION: Finishing specimens of heat cure denture base
      resin with sand paper of progressive grits alone exhibited minimum Candidal
      adherence. Specimens which were finished by using sand papers of progressive
      grits, followed by polishing with pumice reduced Candidal adherence marginally as
      compared to that in control group. Finishing specimens of heat cure denture base
      resin by using above steps, followed by rouge, showed maximum Candidal adherence.

PMID- 24298530
TI  - Use of fisiograft in intrabony defects- a clinical and radiological study.
AB  - AIM: To evaluate the efficacy of Polylactic Acid/Polygycolic Acid (PLA/PGA 
      Fisiograft(r)) with Open Flap Debridement (OFD) and OFD alone in the treatment of
      intrabony defects over a period of 9 months. MATERIAL AND METHODS: Twenty Nine
      systemically healthy subjects with total of 30 defects were included in the
      present, randomized, controlled and two arm parallel study. Tests were treated
      with OFD along with Fisiograft(r) and controls with OFD alone. RESULTS: On intra
      group comparison, clinical parameters at 6 and 9 months showed statistically
      significant results. On comparing between the two groups, the reduction in Defect
      Specific Bleeding Score (DSBS), Defect Specific Plaque Score (DSPS), Probing
      Depth (PD) and gain in Clinical Attachment Level (CAL) revealed no statistical
      significances other than Recession Depth (REC) which was more in controls. The
      mean radiographic parameters at 9 months post-operatively in both the groups were
      statistically significant. However, the inter-group comparison revealed no
      statistically significant values. CONCLUSIONS: The overall results at the end
      study proved that the adjunctive use of Fisiograft(r) was not beneficial when
      compared with OFD alone. CLINICAL SIGNIFICANCE: Synthetic bone replacement graft
      materials are commonly used for periodontal regeneration. The present study was
      conducted by using PLA/PGA reveals no additional benefit over OFD alone in
      treatment of intrabony defects.

PMID- 24298531
TI  - Comparative Study on the Efficacy of Gingival Retraction using Polyvinyl Acetate
      Strips and Conventional Retraction Cord - An in Vivo Study.
AB  - STATEMENT OF PROBLEM: A new material is proposed in dentistry in the form of
      strips for producing gingival retraction. The clinical efficacy of the material
      remains untested. PURPOSE OF THE STUDY: This study aimed to determine whether the
      polyvinyl acetate strips are able to effectively displace the gingival tissues in
      comparison with the conventional retraction cord. MATERIAL AND METHODS: Complete
      metal ceramic preparation with supra-gingival margin was performed in fourteen
      maxillary incisors and gingival retraction was done using Merocel strips and
      conventional retraction cords alternatively in 2 weeks time interval. The amount
      of displacement was compared using a digital vernier caliper of 0.01mm accuracy.
      RESULTS were analyzed statistically using Paired students t-test. RESULTS: The
      statistical analysis of the data revealed that both the conventional retraction
      cord and the Merocel strip produce significant retraction. Among both the
      materials, Merocel proved to be significantly more effective. CONCLUSION: Merocel
      strip produces more gingival displacement than the conventional retraction cord.

PMID- 24298532
TI  - Flexible thermoplastic denture base materials for aesthetical removable partial
      denture framework.
AB  - Conventional fixed partial dentures, implant supported Fixed Partial Dentures
      (FDPs) and removable partial dentures are the most common treatment modalities
      for the aesthetic and functional rehabilitation of partially edentulous patients.
      Although implants and FDP have certain advantages over removable partial
      dentures, in some cases, removable partial dentures may be the only choice which
      is available. Removable cast partial dentures are used as definitive removable
      prostheses when indicated, but location of clasps may affect aesthetics. So, when
      patient is concerned about aesthetics, flexible partial dentures which is
      aesthetically superior to flipper and cast partial dentures, may be considered.
      But for the success of flexible removable partial denture, proper diagnosis,
      treatment planning and insertion technique of this prosthesis is very important,
      which have been thoroughly described in this article. 

PMID- 24298533
TI  - Multidisciplinary approach to the rehabilitation in management of child with
      early childhood caries: a case report.
AB  - The aesthetic requirement of severely mutilated primary anterior teeth in case of
      Early Childhood Caries (ECC) has been a challenge to paediatric dentists. ECC
      involves the upper anterior teeth early in life and by the time the dentist sees
      the child, most of the coronal structure is lost. This article presents the
      clinical sequence of rehabilitation of maxillary anterior primary teeth, and the
      mandibular posterior teeth. 

PMID- 24298534
TI  - Placement of dental implant in a knife edge ridge in anterior aesthetic zone.
AB  - Dental implants are established alternatives for replacing missing teeth. Dental
      implants are artificial tooth root, positioned in the jaw bone, in order to
      sustain the replacement tooth or bridge. Recent advance in dental implant
      technology has made it more convenient, efficient and affordable for patients. In
      the anterior maxilla, esthetic demands not only require well-anchored implants
      but also sufficient soft and hard tissue in order to achieve natural looking
      result. Augmentation of the resorbed alveolar crest can be achieved, for example,
      with onlay bone grafts, membrane techniques, bone distraction and bone splitting.
      This report highlights the placement of implants in compromised alveolar ridges
      with good results. Implant was successfully restored and follow-up done for one
      year. 

PMID- 24298535
TI  - Tonsillolith: a panoramic radiograph presentation.
AB  - Tonsilloliths are calcifications within a tonsillar crypt, involve primarily the
      palatine tonsil caused by dystrophic calcification as a result of chronic
      inflammation. Tonsilloliths are very uncommon and are microscopic. Tonsillar
      concretions sometimes produce symptoms which include non-specific chronic
      halitosis, irritable cough, dysphagia, otalgia and foreign body-like sensation or
      foul taste. Patients with tonsillolithiasis may also be asymptomatic, with their
      lesions being discovered incidentally on panoramic radiographs. This article
      presents an unusual case of multiple bilateral and asymptomatic tonsilloliths
      which were found during a routine panoramic radiographic examination. 

PMID- 24298536
TI  - E.coli Associated Extensive Bilateral Maxillary Osteomyelitis: A Rare Case
      Report.
AB  - With the advent of broad spectrum antibiotics, chronic osteomyelitis of jaw,
      especially of maxilla, has become a rare lesion. Osteomyelitis of jaw is
      associated with a complex microbiota, the most common oral microorganism being,
      Staphylococcus sp. Reported cases of jaw osteomyelitis caused by enteric bacteria
      are very few in literature. Hereby, we are reporting a case of E.coli associated
      osteomyelitis in a diabetic individual who had presented with very aggressive
      bilateral maxillary necrosis. After extensive literature search, to the best of
      our knowledge, this is the first case of maxillary osteomyelitis associated with
      E.coli which we have come across. 

PMID- 24298537
TI  - Hemifacial microsomia: a series of three case reports.
AB  - Hemifacial Microsomia (HFM) is an asymmetric craniofacial malformation which
      results in hypoplasia of the components of the first and second branchial arches.
      There can be various anomalies, which include conductive hearing loss which is
      caused by external and middle ear deformities. HFM is the second most common
      congenital facial anomaly which is seen after cleft lip/palate. For the pre
      surgical evaluation of this anomaly, diagnostic imaging and classification of the
      facial structures, based on OMENS classification, is of prime importance. The
      management of this developmental malformation is multidisciplinary. We are
      presenting a series of three cases with diverse clinical and radiographic
      features which ranged from mild facial asymmetry and ear malformation to facial
      paralysis. 

PMID- 24298538
TI  - Full mouth rehabilitation of severe fluorozed teeth with an interdisciplinary
      approach (6 handed dentistry).
AB  - Whenever the treatment revolves around structural balance and aesthetic harmony,
      the crux remains to be the periodontal health of the existing dentition. In such
      scenarios where restorations and aesthetics are of concern, biologic width (BW)
      is the initial and final frontier. Considering attrition of teeth, the resistance
      which is offered by them is definitely at a lower level as compared to teeth with
      adequate height. Clinical crowns of worn out teeth are seriously handicapped when
      it comes to bearing the occlusal loads, which can be brought back to normalcy by
      crown lengthening . Crown lengthening includes the surgical removal of soft and
      hard periodontal architecture to gain (vertical dimension) a supracrestal tooth
      length, thus allowing a longer clinical crown reestablishment of BW. This paper
      has described the full mouth rehabilitation of severe fluorozed and attrited
      teeth in a 35-year male with the use of an interdisciplinary approach (6 Handed
      Dentistry). 

PMID- 24298539
TI  - Notching in the posterior border of the ramus of mandible in a patient with
      neurofibromatosis type I - a case report.
AB  - Neurofibromatosis Type I (NFI) is a relatively common hereditary, autosomal
      dominant neurocutaneous condition. It is a benign peripheral nerve sheath tumour
      arising from Schwann cells and peripheral fibroblasts. Even though it is a
      neurocutaneous disorder, NF I has significant skeletal manifestations. Oral and
      maxillofacial skeletal structures are also often involved in the form of
      deepening of sigmoid notch, enlarged mandibular canal and notching of inferior
      border of mandible. In this paper, we are reporting a female patient of NF I who
      presented with a notching in the posterior border of ascending ramus of mandible.

PMID- 24298540
TI  - Non-Surgical Management of Mandibular Molar with Multiple Intra-oral Sinus
      Tracts: A Case Report.
AB  - Multiple intra-oral sinus tracts of dental origin are an uncommon condition.
      Patients with this condition may undergo surgical extraction, biopsies and
      antibiotic regimens, but all of them fail with the recurrence of the sinus tract.
      A proper diagnosis and management are important, to avoid any complications. This
      case report has described the conventional root canal treatment of a patient who
      had three distant intra-oral sinuses which had occurred due to an intact tooth
      with pulp necrosis, who had a history of accidentally biting on a hard food
      object and having a periapical radiolucency which indicated a chronic
      periradicular abscess. At follow up examination, the tooth was found to be
      asymptomatic and radiographically, it showed repair of the lesion. 

PMID- 24298541
TI  - Management of severe gag reflex by an unique approach: palateless dentures.
AB  - Gagging is most common protective reflex that prevents the foreign bodies from
      entering trachea. But some patients have abnormally active gag reflex. The
      purpose of this paper was to describe method of managing gagging patients , based
      on modified treatment approaches, starting from impression making to design of
      the prosthesis i.e. palateless denture, to help the patient tolerate prosthesis
      in his/her mouth. 

PMID- 24298542
TI  - Prosthodontic treatment using vital and non vital submerged roots-two case
      reports.
AB  - Residual ridge resorption has been considered as an inevitable consequence after
      extraction of the teeth. There is a gradual loss of the alveolar bone due to the
      pattern of bone remodeling. In spite of the availability of newer treatment
      modalities like endodontic restoration and periodontic procedures for
      preservation of the remaining teeth they are not feasible for the patients in
      severe stages where restoration might not be possible. The only reliable method
      of preserving the remaining bone is by maintaining the functional health of the
      teeth. Over the years, many studies showed that roots which are fractured and
      left behind during extractions are retained into the alveolar bone with no
      evidence of pathosis. Over denture as a treatment option was developed in an
      effort to preserve the remaining alveolar bone by retaining the natural teeth or
      roots. In over denture treatment, the teeth selected as abutments are prone to
      caries and periodontal disease over a period of time, hence evolved the vital or
      non vital root submergence concept. After a thorough radiographic and clinical
      examination, few teeth without pathosis are retained that eventually are
      surgically submerged in the alveolar ridge. After healing, the over denture with
      reaining vital or non vital teeth preserve the integrity of the bone, making the
      treatment an effective and successfull preventive prosthodontic treatment. 

PMID- 24298543
TI  - Treatment of internal resorption with mineral trioxide aggregates: a case report.
AB  - Tooth resorption is a common sequel which follows injuries or irritation to the
      periodontal ligament and/or tooth pulp. The course of tooth resorption involves
      an elaborate interaction among inflammatory cells, resorbing cells, and hard
      tissue structures. The key cells which are involved in resorption are multi
      nucleated giant cells. Internal root resorptions are usually non-symptomatic and
      they are discovered occasionally through periapical radiographs, which reveal
      very defined and regular outlines. Many techniques and materials have been used
      to fill internal resorptive defects. Among them, Mineral Trioxide Aggregates
      (MTAs) have satisfactory properties, which include: biocompatibility, a
      favourable sealing ability, mechanical strength and a capacity to promote a
      periradicular tissue healing. Thus, a Mineral Trioxide Aggregate (MTA) repair of
      a maxillary left central incisor tooth with an inflammatory resorptive defect, in
      the middle third of the root canal, has been reported here. 

PMID- 24298544
TI  - Space maintainers in dentistry: past to present.
AB  - Early orthodontic interventions are often initiated in the developing dentition
      to promote favourable developmental changes. Interceptive orthodontic can
      eliminate or reduce the severity of a developing malocclusion, the complexity of
      orthodontic treatment, overall treatment time and cost. The safest way to prevent
      future malocclusions from tooth loss is to place a space maintainer that is
      effective and durable. An appropriate use of space maintainer is advocated to
      hold the space until the eruption of permanent teeth. This case report describes
      the various changing trends in use of space maintainers: conventional band and
      loop, prefabricated band with custom made loop and glass fibre reinforced
      composite resins as space maintainers. 

PMID- 24298545
TI  - Composite compound odontoma-a case report.
AB  - Composite Compound Odontoma is a rare odontogenic tumour most commonly occuring
      in the anterior region of maxilla. An 11-year-old female patient reported a
      complaint of missing left central incisor. Clinical and diagnostic investigation
      revealed an odontogenic mass in the region of 21. This rare case report appraises
      the clinical diagnosis, surgical and orthodontic intervention which was planned
      and performed for its management. 

PMID- 24298546
TI  - Artefacts: a diagnostic dilemma - a review.
AB  - The significance of proper handling of biopsy specimens is important and obvious
      for any histopathological diagnosis. Accuracy of tissue diagnosis by the
      pathologists is heavily dependent upon the competence of histotechnologists. The
      aim of a good histopathological technique is to produce microscopic preparation
      of tissues, usually stained, that represents as closely as possible, their
      structures in life. But this is not always possible and some sort of tissue
      morphology is bound to be seen. The ability of oral pathologists in interpreting
      a biopsy correctly is directly proportional not only to the quality, but also to
      the quantity of the specimen. There are many ways through which the exact
      interpretation of tissue specimen becomes compromised and the major pitfall is
      the presence of artefacts. These artefacts may occur during surgical removal,
      fixation, processing, embedding, microtomy and staining procedures. It is
      therefore important to identify the common occurring artefacts during
      interpretation of oral biopsies. 

PMID- 24298547
TI  - A boulder in the brain.

PMID- 24298548
TI  - The effects of smoking on the hearing status - a hospital based study.

PMID- 24298549
TI  - Fine Needle Aspiration Cytologic Diagnosis of Lactating Adenoma: Report of two
      Cases.

PMID- 24298550
TI  - Association of genetic variation in calmodulin and left ventricular mass in full
      term newborns.
AB  - Calmodulin II (CALM2) gene polymorphism might be responsible for the variation in
      the left ventricular mass amongst healthy individuals. The aim was to evaluate
      the correlation between left ventricular mass (LVM) and g.474955027G>A
      (rs7565161) polymorphism adjacent to the CALM2 gene. Healthy Polish newborns (n =
      206) were recruited. Two-dimensional M-mode echocardiography was used to assess
      LVM. Polymorphisms were determined by polymerase chain reaction-restriction
      fragment length polymorphism and sequencing analyses. The carriers of the G
      allele of the CALM2 polymorphism had significantly higher left ventricular
      mass/weight (LVM/BW) values, when compared with newborns homozygous for the A
      allele (3.1 g/m(2) versus 2.5 g/m(2), P adjusted = 0.036). The AG genotype of
      CALM2 was associated with the highest values of LVM/BW, exhibiting a pattern of
      overdominance (2.9 g/kg versus 3.1 g/kg versus 2.5 g/kg, P adjusted = 0.037). The
      results of this study suggest that G>A CALM2 polymorphism may account for subtle
      variation in LVM at birth. 

PMID- 24298551
TI  - Persistence or clearance of human papillomavirus infections in women in Ouro
      Preto, Brazil.
AB  - Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for
      development of precursor lesions and cervical cancer. We investigate persistence
      and clearance of HPV infections and cofactors in unvaccinated women. Cervical
      samples of 569 women (18-75 years), received for routine evaluation in the Health
      Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or
      GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to
      collect sociodemographic and behavioral information. Viral infection persistence
      or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4%
      of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most
      persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or
      persistence did not differ between groups infected by HPVs 18, 53, and 67. In low
      risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV
      11, 61, 72, or 81 infected samples were persistent in the follow-up. No
      statistically significant association was detected between persistent HPV
      infections and sociodemographic and behavioral characteristics analyzed. To study
      persistence or clearance in HPV infection allows the identification of risk
      groups, cofactors, and strategies for prevention of cervical cancer. 

PMID- 24298552
TI  - Aqueous extract of Annona macroprophyllata: a potential alpha-glucosidase
      inhibitor.
AB  - Annona genus contains plants used in folk medicine for the treatment of diabetes.
      In the present study, an aqueous extract prepared from Annona macroprophyllata
      (Annonaceae, also known as A. diversifolia) leaves was evaluated on both the
      activity of yeast alpha -glucosidase (an in vitro assay) and sucrose tolerance in
      Wistar rats. The results have shown that the aqueous extract from A.
      macroprophyllata inhibits the yeast alpha -glucosidase with an IC50 = 1.18 mg/mL,
      in a competitive manner with a K(i) = 0.97 mg/mL, a similar value to that of
      acarbose (K(i) = 0.79 mg/mL). The inhibitory activity of A. macroprophyllata was
      reinforced by its antihyperglycemic effect, at doses of 100, 300, and 500 mg/kg
      in rats. Chromatographic analysis identified the flavonoids rutin and
      isoquercitrin in the most polar fractions of A. macroprophyllata crude extract,
      suggesting that these flavonoids are part of the active constituents in the
      plant. Our results support the use of A. macroprophyllata in Mexican folk
      medicine to control postprandial glycemia in people with diabetes mellitus,
      involving active constituents of flavonoid nature.

PMID- 24298553
TI  - Analysis of risk factors for first seizure after stroke in Chinese patients.
AB  - The aim of this study is to assess related risk factors and predict early- and
      late-onset seizure after first-ever stroke. A total of 2474 consecutive patients
      with initial stroke in China from 1997 to 2007 were retrospectively investigated,
      in which, 24 clinical and radiological indexes were used for evaluation. Odds
      ratio (OR) and 95% confidence interval (CI) were calculated by logistic
      regression. A total of 232 (11.1%) of patients developed seizures during a mean
      follow-up period of 18 months, with 123 experiencing early-onset and 109 late
      onset seizure. The independent risk factors for early-onset seizure were large
      lesion (OR = 9.36), subarachnoid hemorrhage (OR = 5.28), initial hyponatremia (OR
      = 2.10), and cortical involvement (OR = 1.33). The independent risk factors for
      late-onset seizure were cortical involvement (OR = 11.84) and large lesion (OR =
      1.87). These results demonstrated that the risk factors for early seizure after
      stroke are large lesion, subarachnoid hemorrhage, and cortical involvement.
      Surprisingly, hyponatremia also predicts seizure in stroke patients. Cortical
      involvement is a major risk factor for late-onset seizure after stroke. 

PMID- 24298554
TI  - Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX
      proteins in prevention of acute gastric lesion.
AB  - Schiff base complexes have appeared to be promising in the treatment of different
      diseases and disorders and have drawn a lot of attention to their biological
      activities. This study was conducted to evaluate the regulatory effect of Schiff
      base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX
      in protection against acute haemorrhagic gastric ulcer in rats. Rats were
      assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg),
      the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative
      groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h,
      all of the groups received ethanol 95% (5 mL/kg) but the normal control received
      Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and
      the stomachs were dissected for histology (H&E), immunohistochemistry, and
      western blot analysis against HSP70 and BAX proteins. The results showed that the
      Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the
      expression of BAX proteins during their gastroprotection against ethanol-induced
      gastric lesion in rats. 

PMID- 24298555
TI  - An influence of immunomodulation on Th1 and Th2 immune response in endometriosis
      in an animal model.
AB  - AIM: To assess the role of the Th1 and Th2 cellular response in the etiology of
      endometriosis observed in a rat model, with the use of the RESAN immunomodulator.
      MATERIALS AND METHODS: A comparative analysis of cytokines in blood serum typical
      of Th1 (TNF-alpha and INF-gamma ) and Th2 (IL-4, IL-6, IL-10) cell response in
      groups of rats, in which RESAN preparation was used as prophylaxis (Gr. I) or
      treatment (Gr. II) of endometriosis. RESULTS: The results indicated an increase
      in the level of cytokines in blood serum typical of Th2 cell response by
      comparing the second and third stages of the experiment in the second group of
      rats and a decrease in IL-4 and IL-10 between III and IV stages. There was a
      significant difference in cytokine levels during the third stage of the
      experiment by comparing I and II groups of rats. In the III group of rats, levels
      of IL-10 significantly increased between the II and III stages of the experiment.
      CONCLUSION: RESAN preparation shows Th2 cell response, inhibiting the development
      of endometriosis in a rat model. Due to successful prophylactic action, one may
      speculate that RESAN vaccine may be effective as a complementary treatment after
      surgical excision.

PMID- 24298556
TI  - Green and rapid synthesis of anticancerous silver nanoparticles by Saccharomyces
      boulardii and insight into mechanism of nanoparticle synthesis.
AB  - Rapidly developing field of nanobiotechnology dealing with metallic nanoparticle
      (MNP) synthesis is primarily lacking control over size, shape, dispersity, yield,
      and reaction time. Present work describes an ecofriendly method for the synthesis
      of silver nanoparticles (AgNPs) by cell free extract (CFE) of Saccharomyces
      boulardii. Parameters such as culture age (stationary phase growth), cell mass
      concentration (400 mg/mL), temperature (35 degrees C), and reaction time (4 h),
      have been optimized to exercise a control over the yield of nanoparticles and
      their properties. Nanoparticle (NP) formation was confirmed by UV-Vis
      spectroscopy, elemental composition by EDX (energy dispersive X-rays) analysis,
      and size and shape by transmission electron microscopy. Synthesized nanoparticles
      had the size range of 3-10 nm with high negative zeta potential (-31 mV)
      indicating excellent stability. Role of proteins/peptides in NP formation and
      their stability were also elucidated. Finally, anticancer activity of silver
      nanoparticles as compared to silver ions was determined on breast cancer cell
      lines. 

PMID- 24298558
TI  - Emerging technologies for hybridization based single nucleotide polymorphism
      detection.
AB  - Detection of single nucleotide polymorphisms (SNPs) is a crucial challenge in the
      development of a novel generation of diagnostic tools. Accurate detection of SNPs
      can prove elusive, as the impact of a single variable nucleotide on the
      properties of a target sequence is limited, even if this sequence consists of
      only a few nucleotides. New, accurate and facile strategies for the detection of
      point mutations are therefore absolutely necessary for the increased adoption of
      point-of-care molecular diagnostics. Currently, PCR and sequencing are mostly
      applied for diagnosing SNPs. However these methods have serious drawbacks as
      routine diagnostic tools because of their labour intensity and cost. Several new,
      more suitable methods can be applied to enable sensitive detection of mutations
      based on specially designed hybridization probes, mutation recognizing enzymes
      and thermal denaturation. Here, an overview is presented of the most recent
      advances in the field of fast and sensitive SNP detection assays with strong
      potential for integration in point-of-care tests. 

PMID- 24298559
TI  - Parahydrogen-induced polarization (PHIP) in heterogeneous hydrogenation over bulk
      metals and metal oxides.
AB  - The results show that, in general, observation of PHIP effects on metals does not
      require the presence of a support. In addition, certain metal oxides can produce
      PHIP effects in the absence of a supported metal. The new promising catalysts for
      producing PHIP heterogeneously have been identified. 

PMID- 24298557
TI  - A genome-wide analysis of RNA pseudoknots that stimulate efficient -1 ribosomal
      frameshifting or readthrough in animal viruses.
AB  - Programmed -1 ribosomal frameshifting (PRF) and stop codon readthrough are two
      translational recoding mechanisms utilized by some RNA viruses to express their
      structural and enzymatic proteins at a defined ratio. Efficient recoding usually
      requires an RNA pseudoknot located several nucleotides downstream from the
      recoding site. To assess the strategic importance of the recoding pseudoknots, we
      have carried out a large scale genome-wide analysis in which we used an in-house
      developed program to detect all possible H-type pseudoknots within the genomic
      mRNAs of 81 animal viruses. Pseudoknots are detected downstream from ~85% of the
      recoding sites, including many previously unknown pseudoknots. ~78% of the
      recoding pseudoknots are the most stable pseudoknot within the viral genomes.
      However, they are not as strong as some designed pseudoknots that exhibit
      roadblocking effect on the translating ribosome. Strong roadblocking pseudoknots
      are not detected within the viral genomes. These results indicate that the
      decoding pseudoknots have evolved to possess optimal stability for efficient
      recoding. We also found that the sequence at the gag-pol frameshift junction of
      HIV1 harbors potential elaborated pseudoknots encompassing the frameshift site. A
      novel mechanism is proposed for possible involvement of the elaborated
      pseudoknots in the HIV1 PRF event. 

PMID- 24298560
TI  - Technology: Tools from scratch.

PMID- 24298561
TI  - Reply: To PMID 17934252.

PMID- 24298562
TI  - Nailing fingerprints in the stars.

PMID- 24298563
TI  - The DIY dilemma.

PMID- 24298564
TI  - Enemy of the good.

PMID- 24298565
TI  - Reply: To PMID 24298561.

PMID- 24298566
TI  - Bone marrow necrosis: a culture medium for bacteria.

PMID- 24298567
TI  - Metastatic Merkel cell carcinoma involving the bone marrow with chronic
      lymphocytic leukemia mimicking Richter transformation.

PMID- 24298568
TI  - Security: Expand nuclear forensics.

PMID- 24298569
TI  - Technology: Sharing data in materials science.

PMID- 24298570
TI  - Operative and perioperative management experience for hepatobiliary malignancies
      following ERCP-related pancreatitis.
AB  - BACKGROUND/AIMS: There have been few papers on how to treat hepatobiliary
      malignancies after ERCP-related pancreatitis focusing on the timing of the
      operation and postoperative complications. The aim of this study was to clarify
      the relationship among the time after the pancreatitis, the complexity of the
      operation, and the characteristic postoperative complications. METHODOLOGY: The
      clinicopathological characteristics of five patients with hepatobiliary
      malignancies who had a prior history of ERCP-related pancreatitis were analyzed.
      RESULTS: The five patients included two with extrahepatic bile duct carcinomas,
      two with ampulla of Vater carcinomas, and one with intrahepatic hilar
      cholangiocarcinoma. The median time to the operation from pancreatitis was 31 (16
      116) days. The median operation time and blood loss were 661 (576-924) min and
      3695 (2730-7240) mL, respectively. Various postoperative complications were seen
      in all cases including acute respiratory distress syndrome and infection of
      peripancreatic necrosis. The postoperative mortality rate was 0%, with a
      morbidity rate of 100%. R0 operations were performed in all five cases.
      CONCLUSIONS: Surgery for hepatobiliary malignancies after ERCP-related
      pancreatitis appears to have a high morbidity rate. The surgery must strike a
      balance between curability of the malignancy and safety with respect to the
      frequent postoperative complications.

PMID- 24298571
TI  - The relation between pathological complete response and clinical outcome in
      patients with rectal cancer.
AB  - BACKGROUND/AIMS: Preoperative chemoradiotherapy (CRT) is the standard treatment
      modality in locally advanced rectal cancer. The primary aim was to correlate
      pathological complete response (pCR) with patient outcome, and the secondary
      objective was to identify predictive factors of pCR. METHODOLOGY: Patients with
      clinical stage II/III rectal cancer who received preoperative CRT between 2002
      and 2010 were retrospectively studied.The median radiotherapy dose was 54 Gy
      (range, 45 to 64 Gy), and all patients received concurrent infusional 5
      fluorouracil-based chemotherapy. RESULTS: Median follow-up time was 48.3 months
      (range, 24 to 96 months) and 51 months (range, 44 to 110 months) for no-pCR and
      pCR groups, respectively. Eighteen patients (18.6%) had pCR. The 5-year overall
      survival was 95% for patients with pCR and 74.8% in patients without pCR
      (p=0.009). The 5-year local relapse free survival was 87.5% and 95% for the no
      pCR and pCR groups, respectively (p=0.09). The 5-year distant relapse free
      survival was 93% in pCR group and 79.8% in no-pCR group (p=0.02). The 5-year
      distant free survival was 94% and 66% in patients with and without pCR,
      respectively (p=0.017). The clinical T4 (p=0.043) and pretreatment
      carcinoembryonic antigen level (CEA) >5ng/mL (p=0.012) were significantly
      associated with a lower pCR rate. In the multivariate logistic regression
      analysis, pretreatment CEA level >5ng/mL (p=0.008) was the only independent
      factor associated with a lower pCR rate. CONCLUSIONS: Patients with pCR after
      preoperative CRT had a significantly improved outcome. Furthermore, the
      pretreatment CEA level was independently associated with pCR.

PMID- 24298572
TI  - Quality of life of elderly Chinese rectal cancer patients after preventative anal
      surgery: a cohort study.
AB  - BACKGROUND/AIM: To assess the QOL in rectal cancer patients after preventative
      anal operation and to discuss the influence of age on perceived quality of life.
      METHODOLOGY: A prospective study of 342 patients with rectal cancer from May 2011
      to January 2012 in the gastrointestinal surgery department was randomly selected
      and divided into the elderly group and the young group, and the differences in
      their QOL assessed by the questionnaire QLQ-C30, after preventative anal surgery
      (7 days) were compared. RESULTS: A total of 207 patients met the study criteria
      and were divided into the elderly group (>=60 years, 107 cases) and the young
      group (<60 years, 100 cases). The incidences of complication with pneumonia
      (p=0.030), wound infection (p=0.024) and ileus (p=0.036) were higher in the
      elderly group. In the QLQ-C30 assessment, the physical function in the elderly
      group was worse (p=0.004). Additionally, the fatigue of symptom, sleep
      disturbance and poor appetite (p<0.001), and global quality of life (p=0.002)
      were worse in the elderly group too. However, the role and emotional function
      were better in the elderly group (p<0.001). CONCLUSIONS: The QOL in elderly
      patients is generally worse than young patients, and a targeted approach should
      be used.

PMID- 24298573
TI  - Clinical significance of insulin-growth factor 1 and insulin-growth factor 1
      receptor expression in gastrointestinal stromal tumors.
AB  - BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors in the gastrointestinal tract and are mostly driven by KIT and
      PDGFRA-activation mutations. However, other signaling pathways are involved in
      pathogenesis and proliferation of GISTs. This study investigates the prognostic
      significance of insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) and
      the role of succinate dehydrogenase subunit B (SDHB) in GISTs. METHODOLOGY:
      Immunohistochemistry (IHC) for IGF1, IGF1R and SDHB was performed in total of 165
      GISTs. RESULTS: The overexpression of IGF1 was evident in tumors with high
      mitotic count, large tumor size and was correlated with high risk of malignant
      behavior. IGF1R overexpression was correlated with IGF overexpression, high
      mitotic count and high risk of malignant behavior. Loss of expression for SDHB
      was found in only 2 gastric GISTs. CONCLUSIONS: The overexpression of IGF1 and
      IGF1R can be useful marker to predict relapse and aggressive behavior in GISTs
      and has prognostic implications.

PMID- 24298574
TI  - Avian-origin H3N2 canine influenza virus circulating in farmed dogs in Guangdong,
      China.
AB  - Since 2006, more and more cases of the infectious H3N2 canine influenza virus
      (CIV) in pet dogs have been reported in Southern China. However, little is known
      about the prevalence situation of H3N2 CIV infections in farmed dogs in China.
      This is the first systematic epidemiological surveillance of CIV in different dog
      populations in Southern China. Two virus strains A/Canine/Guangdong/1/2011(H3N2)
      and A/canine/Guangdong/5/2011(H3N2) were isolated from canine nasal swabs
      collected at one dog farm in Guangzhou and the other farm in Shenzhen. Sequence
      and phylogenetic analysis of eight gene segments of these viruses revealed that
      they were most similar to the newly isolated canine H3N2 viruses in dogs and cats
      from Korea and China, which originated from avian strain. This indicates that
      H3N2 CIV may be a common pathogen for pet and farmed dog populations in Southern
      China at present. Serological surveillance has shown that the infection rate of
      this avian-origin canine influenza in farmed dogs and in pet dogs were 12.22% and
      5.3%, respectively; as determined by the ELISA. The data also suggested that
      transmission occurred, most probably by close contact, between H3N2 CIV infected
      dogs in different dog populations in recently years. As H3N2 outbreaks among dogs
      continue in the Guangdong Province (located very close to Hong Kong), the areas
      where is densely populated and with frequent animal trade, there is a continued
      risk for pet H3N2 CIV infections and for mutations or genetic reassortment
      leading to new virus strains with increased transmissibility among dogs. Further
      in-depth study is required as the H3N2 CIV has been established in different dog
      populations and posed potential threat to public health.

PMID- 24298575
TI  - Octreotide for primary moderate to severe acute pancreatitis: a meta-analysis.
AB  - BACKGROUND/AIMS: To systematically evaluate the effect and safety of octreotide
      on primary moderate to severe acute pancreatitis. METHODOLOGY: The Cochrane
      Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed,
      EMBASE, Science Citation Index Expanded (SCI-E), and Chinese Biomedicine Database
      (CBM) were searched in September 2011. Major outcomes contained mortality,
      incidence rate of complications, rate of surgical intervention, and length of
      hospital stay. RESULTS: Eleven randomized clinical trials with 720 participants
      were included and evaluated, only two of which had a high study quality and were
      combined in meta-analysis. The pool estimate of RR of mortality was 0.88 (95% CI:
      0.53, 1.45) and that of incidence rate of complication was 1.08 (95% CI: 0.94,
      1.26), both of which had no significant difference. The other two outcomes could
      not be combined for lack of enough data. CONCLUSIONS: Present evidence does not
      approve octreotide's benefit in the major outcomes of moderate to severe acute
      pancreatitis and further randomized controlled trials with high quality and large
      sample size are required.

PMID- 24298576
TI  - Analysis of resected gastric cancer in Turkish population.
AB  - BACKGROUND/AIMS: Gastric cancer is still an important health issue in Eastern
      Europe and Middle East, including Turkey, although its prevalence is decreasing
      in the western world. METHODOLOGY: In order to define the profiles of the
      patients operated with a diagnosis of gastric cancer in Turkey, a multicenter
      retrospective study was conducted. RESULTS: Six hundred and forty-eight of the
      840 patients with complete data in all parameters were included in the analysis.
      The median follow-up time was 17.16 months (range, 6-143.63 months). Mean age was
      57+/-11.7 (19-85). There was a recurrent disease in 42% of the tumors located at
      cardia, corpus or antrum, and 86% of diffuse tumors (p<0.0001). The ratio of
      patients with recurrent disease was greater in stage III and IV tumors (52%) than
      stage II (29%) and stage I (17%) tumors. There were also greater recurrence
      ratios in patients with node positive (pN1-3) patients than pN0 tumors, and pT3-4
      tumors than pT1 or pT2 tumors. Any recurrence was found in 48% of the tumors with
      lymphovascular invasion, while in 39% without lymphovascular invasion (p=0.026).
      A statistically significant difference was found in the recurrence status of
      patients with positive / dissected node ratio of <10% and >=10% (p<0.0001).
      CONCLUSIONS: Gastric cancer cases in Turkey are seen at a younger age, and at a
      higher stage. Proximal gastric cancer is seen much less than the western series.
      Prognostic significance of lymphovascular invasion in both univariate, and
      multivariate analyses is noteworthy.

PMID- 24298577
TI  - Author's response.

PMID- 24298578
TI  - Managing uncertainty.

PMID- 24298579
TI  - Ivacaftor. Uncertain harm-benefit balance.
AB  - Cystic fibrosis is a serious genetic disease due to mutations in the gene
      encoding CFTR (Cystic FibrosisTransmembrane conductance Regulator), a protein
      involved in cellular transmembrane transport, particularly of chloride ions.
      Ivacaftor is described as a selective potentiator of CFTR protein. It is now
      licensed for the treatment of cystic fibrosis patients 6 years of age and older
      who carry the CFTR G551D mutation, which is the case for about 4% to 5% of cystic
      fibrosis patients. Two randomised placebo-controlled trials of ivacaftor have
      been carried out in this setting, in a total of 213 patients. The frequency of
      pulmonary exacerbations fell in one of the two trials during the first 48 weeks
      of treatment, but there was no impact on the number of hospitalisations or the
      use of intravenous antibiotics. In both trials, addition of ivacaftor improved
      FEV1 by an average of about 10% at week 24 and increased body weight by an
      average of about 2.5 kg after 1 year. Upper respiratory tract infections occurred
      in the ivacaftor groups during these trials, with more cases of bacterial
      contamination and, possibly, more pulmonary exacerbations in the longer term.
      Ivacaftorcarries a risk of numerous pharmacokinetic interactions that can require
      dose adjustment, particularly for patients with hepatic impairment and those
      receiving cytochrome P450 isozyme 3A inhibitors or inducers. Given the absence of
      data, ivacaftor should be avoided during pregnancy. In practice, in 2013, it is
      not possible to determine the harm-benefit balance of ivacaftor due to the high
      risk of drug interactions, as well as a possible increased risk of infections and
      liver toxicity.

PMID- 24298580
TI  - CFTR mutations and cystic fibrosis.

PMID- 24298581
TI  - Cobicistat + elvitegravir + emtricitabine + tenofovir. Two new drugs, but no
      progress.
AB  - First-line treatment of HIV-1 infection currently consists of a combination of at
      least three antiretroviral drugs belonging to two different classes: for example,
      efavirenz + tenofovir + emtricitabine or lopinavir + ritonavir + tenofovir +
      emtricitabine. Following marketing authorisation in the United States, a
      marketing application has been submitted in the European Union for the fixed-dose
      combination of cobicistat (CYP 3A inhibitor), elvitegravir (HIV integrase
      inhibitor), emtricitabine and tenofovir (HIV reverse transcriptase inhibitors).
      Clinical evaluation is based on two "non-in feriority" trials, one versus
      efavirenz + emtricitabine + tenofovir, and the other versus atazanavir+ ritonavir
      + emtricitabine + tenofovir. Overall, about 85% of patients achieved undetectable
      viral load 48 weeks after treatment initiation. The cobicistat + elvitegravir +
      emtricitabine + tenofovircombination had the usual adverse effects of
      antiretroviral combinations (diarrhoea, nausea, upper respiratory tract
      infections, neuropsychological disorders, etc.), plus musculoskeletal disorders
      and renal toxicity. Cobicistat carries a high risk of interactions. The
      cobicistat + elvitegravir + emtricitabine + tenofovir combination is taken as a
      single daily tablet. In practice, given the lack of therapeutic progress, it is
      best to stick with better-documented antiretroviral combinations.

PMID- 24298582
TI  - Adalimumab and axial spondyloarthritis. Useful for some patients in treatment
      failure.

PMID- 24298583
TI  - Fentanyl buccal film. New oral transmucosal form has no advantages in
      breakthrough pain.

PMID- 24298584
TI  - Ethical apathy.

PMID- 24298586
TI  - INN: -erg-.

PMID- 24298585
TI  - INN: -tibant.

PMID- 24298587
TI  - Proton pump inhibitors: Clostridium difficile infections.
AB  - Data on the adverse effect profile of proton pump inhibitors continue to
      accumulate. In addition to increasing the risk of bacterial pneumonia, proton
      pump inhibitors appear to increase the risk of intestinal Clostridium difficile
      infection. A meta-analysis of epidemiological studies showed a statistically
      significant increase in C. difficile infection among patients taking proton pump
      inhibitors, most of whom were hospital patients.The estimated relative risk was
      1.7 for primary infections (95% confidence interval (95CI): 1.5 to 2.1) and 2.5
      for recurrent infections (95Ch: 1.2 to 5.4). When the proton pump inhibitor was
      coadministered with an antibiotic, the estimated relative risk was 2.0 (95CI: 1.0
      to 3.7). Other meta-analyses published in 2012 provided similar results. A
      similar increased risk has been observed with H2 antagonists. The presumed
      mechanism is the reduction in gastric acidity induced by these drugs. In
      practice, proton pump inhibitors should not be used indiscriminately, especially
      in hospital patients and in persons at increased risk of C. difficile infection.
      Patients should be informed of new data on the adverse effects of the medications
      they are taking so that they can weigh the harms and benefits.

PMID- 24298588
TI  - Trimebutine: abuse, addiction and overdose.
AB  - Trimebutine, an antispasmodic drug, is used to relieve pain associated with
      irritable bowel syndrome, despite a lack of proven efficacy. Trimebutine has been
      shown to act on peripheral opioid receptors. Cases of trimebutine abuse and
      addiction have been reported in young adults, especially with the injectable
      form. Cases of serious accidental or intentional trimebutine overdose have been
      reported in infants and young adults, leading to neurological disorders (loss of
      consciousness, coma, drowsiness and convulsions) and cardiac disorders
      (bradycardia, ventricular tachycardia, arterial hypertension). Time to symptom
      onset was less than 3 hours after trimebutine intake. In practice, trimebutine is
      by no means a harmless drug, contrary to the impression given by the limited
      safety data available. Patients with pain due to irritable bowel syndrome should
      be informed of the adverse effects of trimebutine, and the harm-benefit balance
      should be reassessed in patients already taking this drug.

PMID- 24298589
TI  - NSAIDs: acute kidney injury, in children also.

PMID- 24298590
TI  - ACE inhibitors, angiotensin II receptor blockers and pregnancy: fetal renal
      impairment.

PMID- 24298591
TI  - Proton pump inhibitors: bacterial peritonitis.

PMID- 24298592
TI  - Duloxetine: withdrawal syndromes.

PMID- 24298593
TI  - Strontium: myocardial infarction.

PMID- 24298594
TI  - Goji berries and anticoagulants: bleeding.

PMID- 24298595
TI  - Terbinafine: taste and smell disorders.

PMID- 24298596
TI  - SSRI antidepressants: brain haemorrhage.

PMID- 24298598
TI  - Listeriosis: not only during pregnancy.
AB  - Certain patients are exposed to an increased risk of listeriosis, particularly
      those with chronic lymphocytic leukaemia. It is better to inform them of the
      dietary and hygiene precautions to take to minimise this risk.

PMID- 24298597
TI  - Vitamin D "insufficiency" in adults. Beware of vague concepts with uncertain
      clinical relevance.
AB  - According to certain "reference ranges", about a billion people worldwide,
      including 80% of the French population, have vitamin D insufficiency or
      deficiency. In France, serum vitamin D assay has become commonplace. Between 2010
      and 2011, the number of tests performed increased by about 70%, the most rapid
      growth in any laboratory assay. How are "normal" vitamin D levels and, thus,
      vitamin D insufficiency or deficiency, established, and what is their clinical
      relevance? To answer these questions, we reviewed the literature using the
      standard Prescrire methodology. In early 2013, there is no international
      consensus on normal serum concentrations of 25-hydroxyvitamin D (25(OH)D). Using
      biochemical criteria, some experts define normal vitamin D status as a blood
      25(OH)D concentration above 30 ng/ml and vitamin D insufficiency as levels
      between 20 and 30 ng/ml. The definition of vitamin D insufficiency is disputed by
      other experts, who point out that 97.5% of the general population with vitamin D
      levels of at least 20 ng/ml have no bone disorders. Biostatistical data suggest
      that the normal range of 25(OH)D levels is between 11 and 46 ng/ml, but the lower
      limit appears to vary according to the study population. Epidemiological data
      have shown a link between 25(OH)D concentrations below 20 ng/ml and a variety of
      clinical disorders, including osteoporosis, fractures, cancer, infections, and
      autoimmune diseases. Although these data suggest a possible increase in the risk
      of particular disorders, they provide no information on the harm-benefit balance
      of vitamin D supplementation. A few clinical trials have shown that combined
      calcium and vitamin D supplementation (but not vitamin Dalone) has a modest
      preventive effect on osteoporotic fractures in some subgroups of persons over 65
      years old. Some trials showed that the calcium plus vitamin D combination was
      more effective than calcium alone or placebo in reducing falls among some elderly
      subgroups. Elderly patients were recruited for most of these trials regardless of
      their vitamin D status. Vitamin Dsupplementation carries a risk, albeit very
      small, of vitamin D overdose and hypercalcaemia. Vitamin D plus calcium
      supplementation increases the risk of kidney stones. In practice, when treatment
      with vitamin D is envisaged, there is no need to determine vitamin D status by
      conducting blood tests. In contrast, monitoring calcium levels can help prevent
      overdose.

PMID- 24298599
TI  - Intra-articular hyaluronic acid injection: not for gonarthrosis.
AB  - A meta-analysis of 89 randomised trials suggests that, at best, intraarticular
      hyaluronic acid injection only provides a small relief to patients with
      osteoarthritis of the knee, but that it can provoke both local reactions and
      serious adverse effects.

PMID- 24298600
TI  - Type 1 diabetes: fewer complications with intensive insulin therapy.
AB  - Extended follow-up of participants in the "DCCT" trial showed that, in type 1
      diabetes, aiming for near-physiological blood glucose concentrations from the
      start of therapy reduces the risk of diabetic retinopathy, cardiovascular
      complications and renal impairment.

PMID- 24298601
TI  - Paediatric drugs - who benefits from the European paediatric regulation?

PMID- 24298602
TI  - The powerful influence of pharmaceutical sales representatives.

PMID- 24298603
TI  - Polyphenolic substrates and dyes degradation by yeasts from 25 de Mayo/King
      George Island (Antarctica).
AB  - Antarctica offers a range of extreme climatic conditions, such as low
      temperatures, high solar radiation and low nutrient availability, and constitutes
      one of the harshest environments on Earth. Despite that, it has been successfully
      colonized by 'cold-loving' fungi, which play a key role in decomposition cycles
      in cold ecosystems. However, knowledge about the ecological role of yeasts in
      nutrient or organic matter recycling/mineralization remains highly fragmentary.
      The aim of this work was to study the yeast microbiota in samples collected on 25
      de Mayo/King George Island regarding the scope of their ability to degrade
      polyphenolic substrates such as lignin and azo dyes. Sixty-one yeast isolates
      were obtained from 37 samples, including soil, rocks, wood and bones. Molecular
      analyses based on rDNA sequences revealed that 35 yeasts could be identified at
      the species level and could be classified in the genera Leucosporidiella,
      Rhodotorula, Cryptococcus, Bullera and Candida. Cryptococcus victoriae was by far
      the most ubiquitous species. In total, 33% of the yeast isolates examined showed
      significant activity for dye decolorization, 25% for laccase activity and 38% for
      ligninolytic activity. Eleven yeasts did not show positive activity in any of the
      assays performed and no isolates showed positive activity across all tested
      substrates. A high diversity of yeasts were isolated in this work, possibly
      including undescribed species and conspicuous Antarctic yeasts, most of them
      belonging to oligotrophic, slow-growing and metabolically diverse basidiomycetous
      genera.

PMID- 24298604
TI  - Retraction: Adipocyte-derived microvesicles are associated with multiple
      angiogenic factors and induce angiogenesis in vivo and in vitro.

PMID- 24298605
TI  - Retraction: Identification and characterization of microvesicles secreted by 3T3
      L1 adipocytes: redox- and hormone-dependent induction of milk fat globule
      epidermal growth factor 8-associated microvesicles.

PMID- 24298607
TI  - Responding to Typhoon Haiyan.

PMID- 24298608
TI  - Studying sexual health in the UK.

PMID- 24298609
TI  - China relaxes its one-child policy.

PMID- 24298610
TI  - Eulogy.

PMID- 24298611
TI  - When a patient refuses treatment for a postoperative complication: the ethics of
      postoperative care.

PMID- 24298612
TI  - Influencing elements and treatment strategies associated with the relapse of
      hepatocellular carcinoma after surgery.
AB  - BACKGROUND/AIMS: Long-term prognosis after surgical resection of Hepatocellular
      Carcinoma remains unsatisfactory, mainly because of the high postoperative
      incidence of recurrence and metastasis. An updated knowledge on the influencing
      factors of recurrence and treatment strategies of postoperative recurrence is
      important for clinicians in designing a strategy to optimize the chance of long
      term survival in patients undergoing hepatic resection for HCC. METHODOLOGY:
      Using key words "Hepatocellular Carcinoma", "liver cancer", "resection",
      "postoperative recurrence", "treatment strategy", "therapy", "influencing
      factors", "risk factors", we performed a review of relevant English articles
      based on based on a Medline search before May 2012. RESULTS: Influencing factors
      include tumor size, venous invasion, satellite nodules, cirrhosis, alpha
      foetoprotein, aspartate aminotransferase, alkaline phosphatase levels, hepatitis
      B virus and hepatitis C virus infection, Alpha-foetoprotein mRNA and some
      surgical factors. Treatment strategies include re-resection, transarterial
      chemoembolization, radiofrequency ablation, percutaneous ethanol injection,
      salvage liver transplantation, radioactive seed 125I implantation and other new
      treatment modalities of postoperative recurrent HCC are all used to prolong
      survival in patients with recurrence, and multimodality therapy of above
      mentioned therapies may offer additional benefit. CONCLUSIONS: With advances in
      perioperative detection and therapeutic modalities, results of recurrence after
      resection of HCC will greatly improved.

PMID- 24298613
TI  - The differentiation of autoimmune pancreatitis and pancreatic cancer using
      imaging findings.
AB  - BACKGROUND/AIMS: Differentiation of autoimmune pancreatitis (AIP) and pancreatic
      cancer (PC) is important to avoid unnecessary surgery. The aim of this study was
      to compare various image findings and facilitate the differentiation of these two
      diseases. METHODOLOGY: The radiological features of 36 AIP patients and 36
      patients with resected PC diagnosed at Samsung Medical Center from January 1991
      to October 2010, were compared. RESULTS: Regarding CT/MRI findings, diffuse
      pancreas enlargement, capsule-like rim and delayed homogenous enhancement, were
      significantly more frequent in AIP. For cholangiopancreatography findings, main
      pancreatic duct (MPD) narrowing by >=1/3 of the pancreatic length, skipped
      lesions of the MPD, the presence of side branches at the narrowed MPD portion,
      and smooth and straight intrapancreatic common bile duct stenosis were
      significantly more frequent in AIP. However, according to FDG-PET findings,
      SUVmax, uptake shape and pattern, and uptake by extrapancreatic lesions were not
      significantly different for AIP and PC. CONCLUSIONS: Diffuse pancreas
      enlargement, a capsule-like rim, delayed homogenous enhancement, MPD narrowing of
      >=1/3 of the pancreatic length, skipped lesions and the presence of side branches
      at the narrow MPD portion were found to have high specificity for AIP. These
      findings have great power to differentiate AIP and PC.

PMID- 24298606
TI  - Lysine-specific modifications of p53: a matter of life and death?
AB  - Post-translational modifications provide a fine-tuned control of protein
      function(s) in the cell. The well-known tumour suppressor p53 is subject to many
      post-translational modifications, which alter its activity, localization and
      stability, thus ultimately modulating its response to various forms of genotoxic
      stress. In this review, we focus on the role of recently discovered lysine
      specific modifications of p53, methylation and acetylation in particular, and
      their effects on p53 activity in damaged cells. We also discuss a possibility of
      mutual influence of covalent modifications in the p53 and histone proteins
      located in the vicinity of p53 binding sites in chromatin and propose important
      ramifications stemming from this hypothesis.

PMID- 24298614
TI  - Is the 7th TNM edition suitable for biological predictor in early gastric cancer?
AB  - BACKGROUND/AIMS: The clinical and prognostic value of the previous node
      classification of TNM staging in early gastric cancer (EGC) has been less
      definitive. The aim was to assess the suitability of the revised node staging for
      prediction of clinical behavior of EGC. METHODOLOGY: Between 2005 and 2008, 1,845
      patients were diagnosed with EGC and underwent surgery at Severance Hospitals.
      Clinicopathological characteristics were analyzed with comparisons between sixth
      and seventh TNM staging. RESULTS: When comparing IB with IIA upstaged based on
      seventh staging, poor differentiation, signet ring cell, diffuse,
      undifferentiated types, perineural invasion (PNI), larger size and younger age,
      were more significantly associated with IIA. Clinicopathological factors were
      compared between N0/N1 and N2/N3 based on both staging. In mucosal cancer,
      younger age, diffuse and undifferentiated types were more significantly
      associated with N2/N3 based on seventh staging. In submucosal cancer, larger
      size, poor differentiation, signet ring cell, diffuse, undifferentiated types,
      PNI and deeper submucosal invasion, were more significantly associated with N2/N3
      based on seventh staging. CONCLUSIONS: Upstaging in EGC based on the revised TNM
      staging reflects more aggressive biological behavior of cancer. The new TNM
      staging system may be informative in prediction of biological behavior of EGC as
      well as prognosis and survival.

PMID- 24298616
TI  - [Diabetes mellitus - NAFLD: sequence or cause of type-2 diabetes].

PMID- 24298617
TI  - [Achalasia -- correlation between manometry subtype and treatment success].

PMID- 24298618
TI  - [Obesity -- no association with inflammatory bowel disease].

PMID- 24298619
TI  - [Cirrhosis -- sympathomimetics in refractory ascites].

PMID- 24298620
TI  - [Gastroesophageal reflux -- new treatment option with magnetic tape].

PMID- 24298621
TI  - [Hepatic encephalopathy -- preventative effects of lactulose].

PMID- 24298622
TI  - Reply to: Comments on "Agreement between patients' self-report and physicians'
      prescriptions on non-steroidal anti-inflammatory drugs and other drugs used in
      musculoskeletal disorders".

PMID- 24298623
TI  - [Diverticulosis -- sibling study shows hereditary component].

PMID- 24298624
TI  - [Esophageal carcinoma -- long-term rate of metastasis after endoscopic
      resection].

PMID- 24298625
TI  - [Colorectal cancer -- cetuximab: will the hypomagnesemia treatment have future
      success].

PMID- 24298626
TI  - [Nutritional medicine -- bariatric surgery at centers of excellence is no
      better].

PMID- 24298627
TI  - [Acute liver failure -- does N-acetylcysteine improve the prognosis in
      children?].

PMID- 24298628
TI  - [Hepatocellular carcinoma - metformin reduces the risk of type 2 diabetes in a
      dose-dependent manner].

PMID- 24298629
TI  - [Colorectal neoplasia -- is MR colonography suitable for screening?].

PMID- 24298630
TI  - [Irritable Bowel Syndrome -- good results with group hypnosis].

PMID- 24298631
TI  - [Tropical diseases -- leishmaniasis].

PMID- 24298632
TI  - [Opinion DGVS the IQWiG report for early benefit assessment of aflibercept for
      the treatment of metastatic colorectal cancer according to S 35a SGB V on May 29,
      2013].

PMID- 24298633
TI  - Hereditary breast and ovarian cancer: lessening the burden.

PMID- 24298634
TI  - [Dear colleagues!].

PMID- 24298635
TI  - [The UEMS / EUMS and the European Section / Board Gastroenterology / Hepatology
      (ESBGH].

PMID- 24298636
TI  - [The Patients' rights act].

PMID- 24298637
TI  - [Chances of outpatient specialty specialty care (ASV)].

PMID- 24298638
TI  - Motivating your frogs, Calaveras County can help.

PMID- 24298639
TI  - [Correct coding in practice -- coding is in our own interest].

PMID- 24298640
TI  - The same but different: human-like elephant calls.

PMID- 24298641
TI  - [Chronic constipation -- measurement of colonic transit time with radio-opaque
      markers].

PMID- 24298642
TI  - Is it a bird? Is it a plane? No, it's a mangrove rivulus.

PMID- 24298643
TI  - Learning in workers and drones.

PMID- 24298644
TI  - Guppies reproduce from beyond the grave.

PMID- 24298645
TI  - The soothing pace of a caring mother.

PMID- 24298646
TI  - Why do small animals crouch?

PMID- 24298647
TI  - A new clock for molting.

PMID- 24298648
TI  - Bullies in the workplace.

PMID- 24298649
TI  - [Abstracts of the 114th Congress of the Japanese Society of Otolaryngology. May
      15-18, 2013. Sapporo, Japan].

PMID- 24298650
TI  - New quality measures, tight deadline mark CMS payment rule for ASCs.

PMID- 24298651
TI  - Functional activity of varicose human great saphenous vein at different sites.
AB  - Experiments on isolated preparations of varicose human great saphenous vein
      revealed different sensitivity of the distal and proximal portions to P2X
      receptor agonist alpha,beta-methylene-ATP, but not to norepinephrine and
      histamine. It is suggested that restructuring of the P2 receptor system plays an
      important role in the pathogenesis of varicose veins, which affects the trunk of
      the great saphenous vein in varying degrees.

PMID- 24298652
TI  - Effects of prenatal stress on the activity of the pituitary-ovarian system in
      female rats.
AB  - The comparative analysis of hormonal status was performed in mature female rats
      with experimental deficiency of estrogens, which mothers were exposed to stress
      during pregnancy. High levels of follicle-stimulating hormone and luteinizing
      hormone, and significantly lower amount of estradiol were observed in intact
      prenatally stressed females in comparison with intact non-stressed female rats.
      The increase in the levels of follicle-stimulating hormone and luteinizing
      hormone, and the decrease in estradiol concentration were more pronounced in
      blood serum of prenatally stressed ovariectomized rats as distinct from intact
      non-stressed and prenatally stressed female rats, and non-stressed ovariectomized
      female rats. We can conclude that prenatally stressed ovariectomized rats were
      characterized by an increased sensitivity to exogenous hormonal interventions and
      high lability of functional state of the pituitary-ovarian system.

PMID- 24298653
TI  - Free radical lipid peroxidation in the nuclei of mouse liver cells under normal
      conditions and after partial hepatectomy.
AB  - The dynamics and periodicity of LPO processes in the nuclei and chromatin were
      detected during regenerative processes in mouse liver. LPO processes were
      enhanced in transcriptionally active and replicating chromatin.
      Phosphatidylcholine, phosphatidylinositol, esterified cholesterol, and free fatty
      acids were maximally oxidized during active transcription, and cardiolipin was
      oxidized during active replication. These processes were accompanied by
      periodical changes in activity of antioxidant enzymes. High activity of SOD
      during transcriptional activity of liver cells was typical for nuclear matrix
      attached chromatin, but this parameter decreased during replication. Catalase
      activity significantly increased in the fractions of high salt chromatin and
      nuclear matrix-bound chromatin during replication.

PMID- 24298654
TI  - Specially adapted housing eligibility for amyotrophic lateral sclerosis
      beneficiaries. Interim final rule.
AB  - The Department of Veterans Affairs (VA) is amending its adjudication regulation
      regarding specially adapted housing (SAH). The amendment authorizes automatic
      issuance of a certificate of eligibility for SAH to all veterans and active
      servicemembers with service-connected amyotrophic lateral sclerosis (ALS) rated
      totally disabling under the VA Schedule for Rating Disabilities. The intent and
      effect of this amendment are to establish eligibility for SAH for all persons who
      have service-connected ALS. VA previously amended its Schedule for Rating
      Disabilities to assign a 100-percent disability evaluation for any veteran who
      has service-connected ALS based on the recognition that ALS is a rapidly
      progressive, totally debilitating, and irreversible motor neuron disease that
      results in muscle weakness leading to a wide range of serious disabilities,
      including problems with mobility. Because individuals with ALS quickly reach a
      level of total disability, the change was designed to eliminate the need to
      repeatedly reevaluate veterans suffering from ALS over a short period of time as
      symptoms worsen. Based on that same rationale, this amendment addresses the
      corresponding eligibility for SAH benefits for veterans and servicemembers with
      service-connected ALS. The overall SAH grant approval and oversight process is
      complex and lengthy, with many parts beyond VA's control. This rulemaking
      streamlines one aspect of the process within VA's control, by establishing SAH
      eligibility for all veterans or servicemembers with service-connected, totally
      disabling ALS. By shortening the first stage of the SAH process, this regulatory
      change will assist veterans and servicemembers suffering from ALS in adapting
      their homes before their condition becomes too debilitating. It will also
      lengthen the period during which ALS-afflicted veterans and servicemembers will
      be able to utilize the core SAH benefits. VA also makes non-substantive technical
      amendments for clarity.

PMID- 24298655
TI  - Criteria for a catastrophically disabled determination for purposes of
      enrollment. Final rule.
AB  - The Department of Veterans Affairs (VA) is amending its regulation concerning the
      manner in which VA determines that a veteran is catastrophically disabled for
      purposes of enrollment in priority group 4 for VA health care. As amended by this
      rulemaking, the regulation articulates the clinical criteria that identify an
      individual as catastrophically disabled, instead of using the corresponding
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) and Current Procedural Terminology (CPT[registered trademark]) codes.
      The revisions ensure that the regulation is not out of date when new versions of
      those codes are published. The revisions also broaden some of the descriptions
      for a finding of catastrophic disability. Additionally, the final rule does not
      rely on the Folstein Mini Mental State Examination (MMSE) as a criterion for
      determining whether a veteran meets the definition of catastrophically disabled,
      because we have determined that the MMSE is no longer a necessary clinical
      assessment tool.

PMID- 24298656
TI  - [Thought on sustained immunological control of chronic hepatitis B: peginterferon
      a on the market for ten years].

PMID- 24298657
TI  - [Designing efficacious treatment strategies to achieve sustained immunological
      control of hepatitis infection in HBeAg-positive patients].

PMID- 24298658
TI  - [Response-guided therapy and withdrawal time of peginterferon alpha for HBeAg
      negative chronic hepatitis B].

PMID- 24298659
TI  - [Current understanding of the pathogenic mechanisms of HBsAg and their impact on
      clinical management of hepatitis B].

PMID- 24298660
TI  - [Symposium on treatment of patients with chronic hepatitis B who have an initial
      nucleotide(s)analogue therapy with pegylated interferon alpha].

PMID- 24298661
TI  - [Vitamin D-binding protein as a marker of therapeutic effect in patients with
      chronic severe hepatitis B].

PMID- 24298662
TI  - [Critical flicker frequency for the diagnosis of minimal hepatic encephalopathy].

PMID- 24298664
TI  - [Primary mitochondrial disorders and liver disease].

PMID- 24298663
TI  - [Expression and significance of IL-6 in hepatocellular carcinoma cell lines].

PMID- 24298665
TI  - [Recent perspectives on Notch signaling in normal liver development and
      pathogenesis of liver diseases].

PMID- 24298666
TI  - [Reactivation of hedgehog signaling pathway is common characteristics of
      pathogenesis of all kinds of chronic liver diseases].

PMID- 24298667
TI  - Wisdom, inspiration, and passion capture spirit of annual conference.

PMID- 24298668
TI  - Best practices lead to greater consistency in vendor credentialing.

PMID- 24298669
TI  - FDA issues Unique Device Identification final rule.

PMID- 24298670
TI  - Fast action, team coordination critical when surgical fires occur.

PMID- 24298671
TI  - Successful vendor/OR partnership yields more than $1 million in savings.

PMID- 24298672
TI  - OR business managers steadily gaining clout, financial rewards.

PMID- 24298673
TI  - Business managers' skill sets strengthen return on investment.

PMID- 24298674
TI  - Rise in office-based surgery and anesthesia demands vigilance over safety.

PMID- 24298675
TI  - Raising the bar. Hospital interior design focuses on improving outcomes.
      Interview by Jeff Ferenc.

PMID- 24298676
TI  - Medical equipment and BIM. Advancing the planning process with building
      information modeling.

PMID- 24298678
TI  - Perspectives to converge at PDC Summit.

PMID- 24298677
TI  - Going downtown. Embracing urban concepts in health care campus design.

PMID- 24298679
TI  - Conducting a four-step ES staffing analysis.

PMID- 24298680
TI  - The next generation. Succession planning helps teams to build for the future.

PMID- 24298681
TI  - United front. How ES can partner with nursing and infection control.

PMID- 24298682
TI  - Taking control. Reducing operational costs through smarter energy use.

PMID- 24298683
TI  - No time? No problem.

PMID- 24298685
TI  - Lifting clouds.

PMID- 24298684
TI  - A penny saved.

PMID- 24298686
TI  - Shifting gears.

PMID- 24298687
TI  - Tuned in. J. Anthony Brown interviewed by Lindsey Wahowiak.

PMID- 24298688
TI  - Selling lies?

PMID- 24298689
TI  - Baby steps.

PMID- 24298690
TI  - [A clinical investigation of seven patients with pulmonary tuberculosis who
      developed mixed liver injury during oral anti-tuberculosis treatment].
AB  - BACKGROUND: Liver injury is the most common and clinically significant adverse
      reaction to anti-tuberculosis drugs, sometimes resulting in a fatal outcome. It
      has been reported that liver injury induced by isoniazid and pyrazinamide, which
      has the potential to cause hepatocellular injury, has a risk of becoming severe;
      while an injury induced by rifampicin, which has the potential to cause
      cholestatic injury, rarely becomes severe. However, mixed liver injury has not
      been studied thoroughly. METHODS: Of 321 tuberculosis patients who were admitted
      and treated in our hospital over the past 5 years, 7 patients (2.1 %) who
      developed mixed liver injury due to the use of antituberculosis drugs were
      clinically investigated through their medical records. RESULTS: There were 4 male
      patients and 3 female patients, with a mean age of 66.7 (59-85) years. The mean
      duration from the start of oral anti-tuberculosis drugs to the onset of mixed
      liver injury was 28.5 days. In 2 of the patients, the event occurred within 2
      weeks. Two of them had a total bilirubin level of > 5 mg/dl at the time of
      diagnosis. In 6 of the 7 patients, the liver injury improved on discontinuation
      of the anti-tuberculosis drugs. In the remaining 1 patient, the liver injury
      progressed even after discontinuation of the oral treatment, leading to death.
      CONCLUSION: Since mixed liver injury sometimes results in a fatal outcome, it is
      necessary to take adequate precautions.

PMID- 24298691
TI  - [Use of regular check-ups after completion of treatment for latent tuberculosis
      infection].
AB  - PURPOSE: To evaluate the efficacy of regular examination (primarily by chest
      radiography) following treatment for latent tuberculosis infection (LTBI), we
      attempted to estimate the frequency and time to onset of active tuberculosis
      after completion of LTBI treatment. OBJECTS & METHODS: From the Japanese national
      surveillance data of 2008-2011, we extracted and analyzed the number of active
      tuberculosis cases after the end of LTBI treatment that was registered during
      2008-09. RESULTS: Among LTBI cases registered during 2008-09 (n = 8951), 56
      active tuberculosis cases following LTBI treatment were detected by the end of
      2011. Frequency of onset of active tuberculosis by the end of the second year
      after registration of LTBI cases were as follows: 0.57% (51/8951), all active
      tuberculosis cases; 0.10% (9/8951), smear-positive lung tuberculosis cases; and
      0.22% (20/8951), all bacteria-positive lung tuberculosis cases. In 37 active
      tuberculosis cases for which the date of completion of LTBI treatment was
      available, 12 cases were diagnosed within 1 year and 22 within 2 years of the
      completion of LTBI treatment. CONCLUSION: The frequency of onset of active
      tuberculosis after completion of LTBI treatment was relatively low, but it did
      not decrease with time in the following 2 years. Hence, the validity of regular
      examination should be assessed, rather than specifying the duration of regular
      examinations after completion of LTBI treatment.

PMID- 24298692
TI  - [Medication support and treatment outcome in homeless patients with
      tuberculosis].
AB  - PURPOSE: We conducted a study on factors related to treatment outcome and
      medication support in homeless patients with tuberculosis. METHODS: Participants
      were 433 homeless patients with tuberculosis newly registered in Osaka City
      between 2007 and 2009. We investigated factors related to treatment outcome
      (e.g., length of hospital stay, scheduled duration of outpatient treatment, and
      type of DOTS). Controls were 3,047 non-homeless patients with pulmonary
      tuberculosis newly registered in Osaka City during the same period. RESULTS:
      Regarding medication support, 219 (70.4%) of the 311 patients with successful
      treatment received DOTS and completed the treatment during their hospital stay.
      Thirty-five (72.9%) of the forty-eight patients who did not complete treatment
      left the hospital at their own discretion, resulting in treatment
      failure/default. The rate of treatment failure/default in the homeless patients
      with pulmonary tuberculosis was 11.0%, significantly higher than that of non
      homeless patients with pulmonary tuberculosis (6.5%; P < 0.001). Among the 102
      patients receiving community DOTS, medication compliance occurred at least 5 days
      a week in 66 patients (64.7%) and treatments failed or were interrupted in 10
      patients (9.8%). The mean hospital stay was 2.0 +/- 1.6 months in patients with
      failed/defaulted treatment and 4.4 +/- 2.5 months in those with successful
      treatment. The scheduled duration of outpatient treatment was 7.9 +/- 2.7 months
      in patients with failed/defaulted treatment and 3.6 +/- 2.1 months in those with
      successful treatment. Shorter length of hospital stay and longer scheduled
      duration of outpatient treatment were associated with a higher rate of treatment
      failure/default (P < 0.01). CONCLUSION: Homeless patients with tuberculosis had a
      higher rate of treatment failure/default, most likely due to leaving the hospital
      at their own discretion. Patients with successful treatment generally completed
      treatment during their hospital stay. In contrast, patients who received
      community DOTS after discharge from the hospital had a higher rate of treatment
      failure/default, despite receiving medication at least 5 days a week. This
      suggests the need for adequate support, particularly in patients with a shorter
      hospital stay and those with a longer scheduled duration of outpatient treatment.

PMID- 24298693
TI  - [Efficacy of the treatment for latent tuberculosis infection and delayed
      reactivation of tuberculosis].
AB  - PURPOSE: To evaluate the efficacy of treatment for latent tuberculosis infection
      and delayed reactivation of tuberculosis. METHOD: During a large tuberculosis
      outbreak, 129 individuals who were in close contact with tuberculosis patients
      and subsequently tested strongly positive by the tuberculin skin test were
      followed up for 10 years after identification of the source case. RESULT: Of the
      129 individuals, 105 received treatment for latent tuberculosis infection for 6
      months as per recommendation, while the remaining 24 did not receive treatment,
      because most of them were above 30 years of age and were therefore discouraged
      from receiving treatment, as was done in the earlier times in Japan. Of the 105
      individuals, 5 (4.8%) were newly diagnosed with tuberculosis, and the average
      duration from identification of the source case to reactivation of tuberculosis
      was 53 months. Of the 24 individuals who did not receive treatment for latent
      tuberculosis infection, 6 (25.0%) were newly diagnosed with tuberculosis, and the
      average duration from identification of the source case to reactivation of
      tuberculosis was 8.2 months. CONCLUSION: The risk of active tuberculosis was
      reduced by 81.0% with treatment for latent tuberculosis infection, compared with
      that without treatment. Delayed reactivation of tuberculosis was observed among
      patients treated with isoniazid for latent tuberculosis infection for 6 months.

PMID- 24298694
TI  - [A case of tuberculosis that occurred during treatment of hepatocellular
      carcinoma with sorafenib].
AB  - A 66-year-old man with hepatocellular carcinoma (HCC) and suspicion of lung
      metastasis consulted us because of an abnormal chest shadow as seen on a
      radiograph. He had been treated with sorafenib for 2 months. A chest CT scan
      showed cavitating nodules in the left upper lobe that were present before therapy
      with sorafenib, and infiltrative shadows in the subpleural areas of the right
      upper lobe. The shadows were diagnosed, at least in part, as pulmonary
      tuberculosis by using a nucleic acid amplification test for Mycobacterium
      tuberculosis in the sputum that yielded a positive result. Treatment with
      antituberculosis drugs resulted in a good clinical response. However, the patient
      died of HCC. We concluded that the nodule in the right upper lobe was old
      pulmonary tuberculosis, because it did not change during the course of the
      disease and because the cavities in the left upper lobe were active lesions.
      Sorafenib is a molecularly targeted agent that has been proven effective for
      treating advanced HCC with extrahepatic metastasis. It may also cause necrosis
      within lung metastases as an anti-tumor effect. Therefore, pulmonary
      tuberculosis, including reactivation, should be considered in the differential
      diagnosis when treating a patient with sorafenib.

PMID- 24298695
TI  - [Tuberculosis Annual Report 2011--(4) Tuberculosis treatment and treatment
      outcomes].
AB  - The frequency of re-treatment among newly notified tuberculosis (TB) patients
      might be an indicator of inadequate prior treatment. In 2011, 22,681 patients
      were notified with TB, of which, 1,687 patients had received prior TB treatment
      (7.6% of those patients who presented with unknown treatment history were
      excluded). Nearly half of the re-treatment cases had received previous treatment
      after 2000 (n = 766). A standardized treatment regimen is the key to TB control.
      As for the initial treatment regimen, a combination of isoniazid, rifampicin,
      pyrazinamide, and ethambutol (or streptomycin) is recommended; this regimen was
      initially used for the treatment of approximately > or = 85% of all forms of TB
      in patients aged 15-54 years (patients with an unknown treatment regimen were
      excluded). Of the 11,556 patients who underwent TB treatment regimen with
      pyrazinamide and completed the course of treatment by the end of 2011,
      approximately 10% were unable to complete the 2-month-long regimen with
      pyrazinamide. In 2011, 17,519 patients were newly notified with pulmonary TB
      (PTB). The proportion of patients who were hospitalized on the commencement of
      anti-TB treatment increased as the age increased above 30 years. The median
      duration of hospitalization among newly notified TB patients in 2010 was 70 days
      for new sputum-smear positive PTB patients, 71 days for re-treatment sputum-smear
      positive PTB patients, 43 days for other bacteriologically positive PTB patients,
      41.5 days for bacteriologically negative and other patients, and 46 days for
      extra-pulmonary TB patients. As of end-of-year 2011, the median treatment
      duration for all forms of TB patients, newly notified in 2010, was 272 days. The
      treatment success rates for new sputum-smear-positive PTB patients (n = 8,242),
      re-treatment PTB patients (n = 794), other bacteriologically positive PTB
      patients (n = 6,358), and bacteriologically negative and other patients (n =
      2,883), registered in 2010 were 52.0%, 42.7%, 59.6%, and 60.4%, respectively. The
      proportion of new sputum-smear-positive PTB patients, registered in 2009 and
      2010, who died by the end of the following years were 26.9% and 27.8%,
      respectively. The cause of death among TB patients, usually determined by
      physicians, has been collected through a TB surveillance system in Japan. The
      proportion of deaths caused by TB within one month of registration, among both
      the newly notified TB patients and the new sputum-smear-positive PTB patients,
      tended to be higher than that caused by other reasons (48.5% vs. 17.3% and 51.5%
      vs. 19.7%, respectively).

PMID- 24298696
TI  - Faced with problems, persistent people enable a peer solution.

PMID- 24298697
TI  - Study of AOT cost-effectiveness in NYC stirs national debate.

PMID- 24298698
TI  - Compromise shapes innovations in Iowa's Medicaid Expansion.

PMID- 24298699
TI  - Accreditation: new capabilities, new faces.

PMID- 24298700
TI  - Fraud in New Mexico: credible? Incredible?

PMID- 24298701
TI  - The 2013 IT Vendor Survey.

PMID- 24298702
TI  - Beyond the EHR: a simpler future?

PMID- 24298703
TI  - Thinking customization? Proceed with caution.

PMID- 24298704
TI  - Mental health assessment drives change in US employment guidance.

PMID- 24298705
TI  - NIATx collaboratives offer seven strategies for better billing.

PMID- 24298706
TI  - A place for plants to grow and people to recover.

PMID- 24298707
TI  - Mhealth and video conferencing: better care in rural North Carolina.

PMID- 24298708
TI  - [Sustainable medicine and medical responsibility].

PMID- 24298709
TI  - [Chronic lymphocytic leukemia: when to start a specific treatment?].
AB  - This paper reviews the literature to propose guidelines for managing patients
      with early-intermediate stage chronic lymphocytic leukemia (CLL). Clinical and
      biological parameters are sufficient to identify a cohort of patients with high
      risk CLL at diagnosis who will have disease progression: anemia (Hb < 100 g/l) or
      thrombocytopenia (platelets < 100 G/l), bone marrow infiltration (> 30%
      lymphocytes), a rapid doubling time (less than 6 months) or lymphocytes above 300
      g/L, splenomegaly and massive lymphadenopathy, systemic symptoms, uncontrolled
      autoimmune complications. Patients without those characteristics have low-risk
      CLL. In the absence of evidence of survival benefit in low-risk CLL, there is no
      indication for treatment and patients should be followed up by physical
      examination and complete blood count once or twice a year.

PMID- 24298712
TI  - [Electrocardiogram for diagnosing myocardial infarction in patients with left
      bundle branch block or a pacemaker].
AB  - Effective management of myocardial infarction with ST segment elevation depends
      on rapid diagnosis. The presence of a left bundle branch block or of an
      electrically driven rhythm limits the interpretation of the initial
      electrocardiogram, potentially causing damaging delays. The Sgarbossa's score is
      well fit for those situations allowing when positive to opt for an immediate
      reperfusion strategy. However, its low sensitivity requires that it be combined
      with other diagnostic tools when negative.

PMID- 24298710
TI  - [Invasive procedures and long-term anti-coagulation: to bridge or not to
      bridge?].
AB  - Long-term oral anticoagulation is prescribed to 1% of the population to lower
      thrombotic risk associated with venous thromboembolic disease (VTD), atrial
      fibrillation (AF), and cardiac mechanical valve. Annually, 10% of patients with
      at least one of these conditions undergo an invasive procedure. In such case,
      bridging anticoagulation with short half-life parenteral molecules is frequently
      performed to lower the peri-procedural thrombotic risk. Nevertheless, available
      evidence suggests an increase bleeding risk is associated with the bridging
      procedure and recommendations regarding bridging are followed in less than one
      third of cases. Bridging should be considered only if the thromboembolic risk is
      high such as recent VTD (< 3 months), AF with past history of stroke or transient
      ischemic attack, and cardiac mechanical valve.

PMID- 24298713
TI  - [Threshold for allogeneic red cell transfusions in adult patients].
AB  - Red cell concentrate is a life-saving but expensive and sometimes limited
      resource. Its use is associated with a wide range of rare but potentially severe
      complications. Adequate red cell transfusion is critical in terms of costs,
      resource utilization and safety. Transfusion thresholds have been widely debated
      and recent evidence suggest that a restrictive transfusion strategy may allow
      safely reducing the use of red cell concentrates and even improving clinical
      outcomes in some situations. The aim of this article is to review the physiologic
      adaptive responses to anemia and to discuss the clinical evidence about
      erythrocyte transfusion strategies in adult patients in order to provide evidence
      based transfusion recommendations.

PMID- 24298711
TI  - [Procalcitonin: should it be measured systemically?].
AB  - Procalcitonin (PCT) is a biomarker that is increasingly being used to help in
      decision making when managing febrile patients. This is a non exhaustive review
      of the literature regarding the use of PCT in deciding to begin or discontinue
      antibiotic treatment. PCT appears to be useful in patients with respiratory
      infections or sepsis. In both these situations and using evaluated algorithms, a
      low PCT (< 0.25 microg), enables withholding or discontinuing antibiotic
      treatment, without negatively affecting clinical outcomes. For other indications
      there is however insufficient evidence to support the systematic measurement of
      PCT in all febrile patients. In particular, in patients with autoimmune disease
      or in the postoperative setting, PCT is insufficiently sensitive or specific to
      rule out or confirm a bacterial infection requiring antibiotic treatment.

PMID- 24298714
TI  - [Recurrent Clostridium difficile infections: the importance of the intestinal
      microbiota].
AB  - Clostridium difficile infections (CDI) represent 20-30% of diarrhea caused by
      antibiotics and relapse in more than 25% of cases after treatment with
      metronidazole or vancomycin. Given the high prevalence of CDI and the significant
      rate of recurrence despite successful initial treatment, CDI therapy represents a
      real challenge. A better understanding of the intestinal microbiota and its role
      in CDI opens the way to promising new therapeutic approaches, such as fecal
      transplantation. The studies published to date, although few, conclude a certain
      effectiveness of fecal transplantation in recurrent CDI. Further studies are
      needed to confirm its effectiveness, determine the long-term consequences as well
      as good administration practices.

PMID- 24298715
TI  - [Chronic obstructive pulmonary disease: I. Long-term prognostic scores].
AB  - The chronic obstructive pulmonary disease or COPD will probably be in the year
      2020 the third cause of death in the world. It appears therefore appropriate to
      try to make available tools capable of assessing the prognosis of patients with
      this disease. In the first part of this series of two papers, the question of the
      prognosis of stable COPD over several years is addressed. Eight prognostic scores
      are discussed, all of them published between 2004 and 2012. Their components and
      characteristics are analysed and commented upon, with, in particular, emphasis on
      their discriminating power. An Internet program (www.medhyg. ch/scoredoc)
      supplements this review.

PMID- 24298716
TI  - [The extraordinary development of a toolbox in general medicine. Technical,
      clinical and communication tools].

PMID- 24298717
TI  - [Genetics in the assault of cholesterol; Europe in organ failure ].

PMID- 24298718
TI  - [Read Tolstoy or revise the patho?].

PMID- 24298719
TI  - [Scientific publications: the Ocorrafoo Cobange symptom].

PMID- 24298720
TI  - [Nobel 2013 awarded to three descramblers of the cellular machinery].

PMID- 24298722
TI  - [Nietzsche identity and counter-identity ].

PMID- 24298721
TI  - [A neuroprosthesis center has French-speaking rehabilitation clinic].

PMID- 24298723
TI  - [Cardiac amyloidosis, about an atypical case].
AB  - A 64 year old patient with heart failure due to primary cardiac amyloidosis is
      described. This case offers the opportunity to review the literature dealing with
      the cardiac involvement associated with this disorder and the differential
      diagnosis of restrictive heart disease.

PMID- 24298724
TI  - [Sitagliptin in the treatment of type 2 diabetes: insights five years after
      commercialisation].
AB  - Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4
      commercialized for the management of type 2 diabetes. It is also available as a
      fixed-dose combination with meformin (Janumet). Almost 5 years after its launch
      in Belgium, the present review summarizes the most recent data regarding the
      clinical efficacy of this antidiabetic agent, the controversy about its safety
      profile, its use at lower dosage in case of moderate to severe renal
      insufficiency, the various indications that have been successively accepted and
      reimbursed, and, finally, the perspectives offered by a large ongoing
      cardiovascular outcome trial (TECOS).

PMID- 24298725
TI  - [New guidelines for hypertension management in 2013].
AB  - The 2013 guidelines for arterial hypertension have just been released by the
      European Societies of Cardiology and Hypertension. As already discussed in
      earlier versions, the decision to treat must be based on the assessment of the
      cardiovascular risk. The value of out-of-the office blood pressure measurements
      to confirm the diagnosis of hypertension is underlined and the authors stress the
      need for a close follow up of non pharmacological therapeutic measures. A
      novelty, however, consists in the simplification of the blood pressure target
      under treatment, which must be < 140/90 mmHg in the vast majority of patients,
      except for octogenerians whose systolic blood pressure target should be < 150
      mmHg. For resistant hypertension, renal denervation and carotid baroreceptor
      stimulation are proposed as new invasive modes of therapy; their clinical values,
      however, remain to be confirmed.

PMID- 24298726
TI  - [Antipsychotics in depression].
AB  - Depression is a major public health problem. In the treatment of depression, the
      main objectives must be complete remission and prevention of recurrence. However,
      the objective of remission remains difficult in clinical practice. Several
      pharmacological strategies exist to handle treatment resistant depression and
      achieve remission. Among these options, addition of an atypical antipsychotic has
      become a popular choice. Second generation antipsychotics have been investigated
      in clinical trials in treatment resistant depression and in bipolar depression.
      Scientific data are available particularly for aripiprazole and quetiapine XR.

PMID- 24298727
TI  - [Cancer diagnosis during pregnancy: importance of a national and European
      registration].
AB  - Cancer during pregnancy is relatively rare, but its incidence has been increasing
      over recent years. A European study has been launched in 2005 by F. Amant (KUL)
      to register all pregnant patients with a cancer diagnosis with or without
      treatment during pregnancy (surgery, chemotherapy and/or radiotherapy). All
      infants exposed to chemotherapy and/or radiotherapy are also followed up by
      pediatricians, neurologists, cardiologists and psychologists. In Belgium, French-
      and Dutch- language hospitals are working in close collaboration to follow these
      pregnant patients. The national results are summarized in this paper.

PMID- 24298728
TI  - [Neonatal hyperthyroidism: clinical pattern and therapy].
AB  - Neonatal hyperthyroidism is a rare pathology, most often the consequence of
      Graves' disease in the mother. Around 0.2% of pregnant women have Graves disease
      and 1 to 2% of newborns of mother with Graves' disease. This article will
      describe the case of 4 newborns who have been diagnosed and treated in CHU-NDB
      between 2007 and 2011. The second part will focus on the new recommendations
      about the management of these young patients from foetal period to birth.

PMID- 24298729
TI  - [Perioral myoclonia syndrome with absences: about 2 cases].
AB  - Perioral myoclonia with absences (POMA) was first described in 1994 by CP
      Panayotopoulos who identified 6 cases that did not fit with the classical
      syndrome of absence epilepsy in children and whose predominant symptom during the
      absence seizure was the occurrence of myoclonia of perioral muscles. The POMA
      belongs to the group of generalized idiopathic epilepsies. It begins in childhood
      and there is a female predominance. It may be accompanied by tonic-clonic
      generalized seizures as well as absence status epilepticus. It has the EEG
      characteristics of typical absence seizures and therefore remains currently
      considered as such. The clinical manifestations of POMA are often misdiagnosed as
      focal motor seizures. This syndrome can be pharmacoresistant and is not likely to
      regress spontaneously. We present two clinical observations of perioral myoclonia
      with absences. The first case illustrates the typical electro-clinical features
      of this syndrome while the second illustrates its pharmacoresistance.

PMID- 24298730
TI  - [How to explore and treat ... a mucous otitis in the child].
AB  - About nine children out of ten present at least one episode of otitis media with
      effusion (OME) before school age and near a third suffer from persistent or
      repetitive OME, which involves a higher risk of speech difficulties and of
      reduced learning abilities. The care of children with repeated or persistent OME
      remains a debated topic. The assessment of the risk of speech difficulties should
      go beyond the quantification of the hearing deficit. It should also take into
      account the context in which the disorder has developped and detect any
      comorbidity from which the child might suffer. Based on these various
      considerations, it will be necessary to assess the value of an immediate surgical
      treatment as opposed to the risks of a prolonged observation period.

PMID- 24298731
TI  - [Hokusai-VTE: edoxaban versus warfarin for the treatment of symptomatic venous
      thromboembolism].
AB  - Currently venous thromboembolic disease (VTE), i.e. deep venous thrombosis and
      pulmonary embolism, remains a major cause of morbidity and mortality all around
      the world. The Hokusai-VTE study is a randomized, double-blind trial to evaluate
      whether initial heparin (5 days) followed by the oral Xa factor inhibitor
      edoxaban (60 mg once daily) may be an alternative to the standard therapy, i.e.
      heparin (5 days) followed by warfarin (INR of 2.0-3.0) for the prevention of
      recurrent thromboembolism in patients with acute symptomatic VTE. In patients
      with VTE, including pulmonary embolism with right ventricular dysfunction,
      treatment with heparin followed by oral edoxaban 60 mg once daily was non
      inferior to the standard treatment with respect to efficacy and superior with
      respect to bleeding (fewer fatal and intracranial bleeds, but no statistical
      significance regarding major bleeding). Reducing the dosage of edoxaban to 30 mg
      once daily is safe in case of renal impairment and low body weight.

PMID- 24298732
TI  - [Use of free vascularized fibular graft flap in the treatment of large bone
      defects after limb injury].
AB  - Free vascularized fibular graft is of the greatest importance in the orthopaedics
      and trauma. Bone, skeletal defects due to the trauma, infections and congenital
      anomalies could be successfully solved by the free vascularized fibular grafts.
      In this article the main anatomical data of fibular graft, surgical techniques,
      indications for the FVFG in the treatment of trauma caused bone defects or its
      complications -sequels are described.

PMID- 24298733
TI  - Disruption of the knee extensor apparatus complicating anterior cruciate ligament
      reconstruction.
AB  - Disruption of the knee extensor apparatus, after harvesting the central third of
      the patellar tendon for a bone-tendon-bone autograft, is a rare complication. We
      made 2215 reconstructions of the anterior cruciate ligament of the knee using
      bone-patellar tendon-bone technique, and 10 patients had fracture of the patella
      (0.45%), and fore patients had rupture of the patellar tendon (0.18%). The
      fracture of the patella in two patients was treated nonoperatively and 8 patients
      was treated with operative reduction and osteosynthesis. Reconstruction of the
      patellar ligament in four patients with a rupture of patellar tendon (0.18%) was
      performed by a technique previously published with BTB allograft taken from the
      local bone bank. The mean Lysholm score was 90 (85-100), and all of them have
      continued to engage in sporting activities. In all patients the Lachman test was
      with the firm stop compared to the other leg. X-ray changes in the patella were
      found in 2 patients, who had multifragmentary fractures of the patella.
      Disruption of the knee extensor apparatus, after harvesting the central third of
      the patellar tendon for a bone-tendon-bone autograft, can be prevented by
      avoiding to take too much bone graft, by using the most precise tools for
      cutting, while rehabilitation must be carefully planned. The optimal treatment
      disruption of the knee extensor apparatus after the reconstruction of the
      anterior cruciate ligament is a operative reconstruction, which allows
      continuation of the rehabilitation program.

PMID- 24298734
TI  - Replantation of upper extremity, hand and digits.
AB  - Replantation is defined as reattachment of the part that has been completely
      amputated and there is no connection between the severed part and the patient. In
      Boston in 1962 Malt successfully replanted a completely amputated arm of a 12
      year-old boy. Komatsu and Tamai reported the first successful replantation of an
      amputated digit by microvascular technique. There are no strict indications and
      contraindications for replantation. It's on surgeon to explain to the patient the
      chances of success of viability, expected function, length of operation,
      hospitalization and long rehabilitation protocol. Survival and useful function in
      replantation of upper extremity amputations is questionable. Success depends on
      microvascular anastomoses, but the final function is related with tendon, nerve,
      bone and joint repair.

PMID- 24298735
TI  - Distal radius fractures--systematic review.
AB  - Distal radius fractures are an increasingly prevalent upper extremity injury,
      especially among elderly patients. They represent approximately 3% of all upper
      extremity injures. Severity of these fractures is directly related to bone
      mineral density of the patient, and clinical results are dependent on this
      parameter as well. There is a bimodal distribution of these injuries, with a peak
      between 18 to 25 years of age, predominantly male population and a second peak in
      the elderly, older than 65 years, predominantly female population. Early reports
      of fractures of the distal radius considered these fractures to be group of
      injuries with a relatively good prognosis irrespective of the treatment given.
      When it comes to complex fractures, regardless of the method applied, major or
      minor functional invalidity persists. With that in mind fractures of the distal
      radius are medical, social and economic problems of modern society.

PMID- 24298736
TI  - Dilemmas in the treatment of tibial diaphyseal fractures.
AB  - INTRODUCTION: Tibial fractures accompanied by radius fractures at typical sites
      are the most common type of fractures. OBJECTIVE: The study is aimed at using the
      examined sample to make an efficient and economically acceptable choice in the
      treatment of tibial diaphyseal fractures. MATERIAL AND METHODS: The series
      comprises a retrospective and prospective study of the treatment of 131 fresh
      tibial fractures: 31 in women (23.66%) and 100 in men (76.34%) of the average age
      of 37.89. Nineteen patients (14.50%) were treated conservatively and 112 (85.50%)
      surgically: 22 (16.79%) with anti-rotation intramedullary nails, 74 (56.49%) with
      Mitkovic external fixator type M20, and 16 (12.21%) with locking compression
      plate. General anaesthesia was used in 46 patients (35.11%), while spinal
      anaesthesia was used in 85 of them (64.89%). RESULTS: According to the Karlstrom
      Olerud scoring system, the treatment results were as follows: for the 22 tibiae
      treated with anti-rotation intramedullary nails: in 15 (68.18%) the results were
      excellent, in 3 (13.64%) they were good and in 4 (18.18%) they were poor. As for
      the results for the 74 tibiae treated with Mitkovic external fixator type M20,
      they were as follows: in 62 (83.78%) excellent, in 9 (12.16%) good, and in 3
      (4.05%) they were poor. The results for the 16 patients treated with locking
      compression plate were excellent in 10 (62.50%), good in 2 (12.50%) and poor in 4
      patients (25.00%). The treatment results for the 19 tibiae treated with plaster
      cast were excellent in 12 patients (63.16%), good in 2 (10.53%) and poor in 5
      (26.32%). The definite results for the 131 fractured tibiae treated with the
      aforementioned techniques were as follows: excellent in 99 (75.57%), good in 17
      (12.98%) and poor in 15 patients (11.45%). DISCUSSION: There is a variety of
      controversial positions concerning the treatment of the tibial diaphysis.
      CONCLUSION: On the basis of the results of surgical treatment for the given
      series, the number of surgical interventions, the price of osteosynthetic
      material, my preferences in treating tibial diaphyseal fractures would be as
      follows: Mitkovic external fixator type M20, anti-rotation intramedullary nails
      and locking compression plate. Conservative treatment is indicated when the X-ray
      examination confirms that the fragments have a position acceptable for
      conservative treatment with plaster cast.

PMID- 24298737
TI  - Nature and results of treatment of war wounds caused by cluster bombs.
AB  - The aim of this study is to describe the nature of war wounds with fracture
      caused by cluster bombs and to suggest treatment options for such injuries. The
      nature of wounds caused by cluster bombs differs from those caused by
      conventional arms (they are more severe). The sides of the wounds are represented
      by conquasated soft tissues (such as fat and muscle) with thick dead tissues,
      ordinarily with a thickness of 0.5-4.5 cm. Another main characteristic of such
      injuries is the high percentage of amputations needed due to the high rate of
      neurovascular damage. This paper investigates the cases of 81 patients who
      sustained a total of 99 war wounds with fractures. The average age of the
      patients was 32.7 years while the youngest was 20 and the oldest, 77. According
      to The International Committee of the Red Cross (ICRC) classification of war
      wounds, 14 patients had grade I injuries, 48 patients grade II, and 29 patients,
      grade III. Mitkovic external fixation system, known also as the "War Fixator" was
      used for all fractures fixation. One protocol, which was a modification of the
      ICRC's protocol adapted to our specific conditions, was used throughout the
      study. For solving soft tissue defects, a rotator fasciocutan flap was the most
      frequently used. For solving of bones defect Mitkovic reconstructive external
      fixation device was used. All fractures we treated healed. We concluded that
      shortening the procedural time and being a very simple, immediate using of
      Mitkovic versatile external fixator ("War Fixator") is, leads to desirable
      results.

PMID- 24298738
TI  - Operative treatment of metacarpal and phalangeal fractures with Kirschner wire
      fixation--a review.
AB  - Although hand fractures are most common fractures treated in orthopedic practice,
      many practicians treat them as trivial injuries. Improperly managed they can
      cause consequences and impair hand function. Metacarpal and phalangeal fractures
      are classified based on geometry, anatomic localization and wound presence and
      treatment depend on mechanism of injury. Many of them can be treated
      nonoperatively with reposition and immobilization, but in some cases
      osteosynthesis is a method of choice. Surgeon can choose various range of
      fixation material, and choice depends on fracture type and surgeons affinity.
      Kirschner wire fixation is one of the most frequently used operative procedure
      for hand fracture treatment. It provides good stability, early mobilization and
      excellent functional result.

PMID- 24298739
TI  - Surgical treatment of the unstable type C pelvic injury.
AB  - Rotationally and vertically unstable injuries to the pelvic ring (Type C) require
      stabilisation of the anterior and posterior pelvic ring complex. Inadequate
      treatment of these injuries leads to chronic instability of the pelvic ring,
      which can finally cause permanent disability. Open reduction and stable internal
      fixation of the anterior and posterior complex of unstable pelvic ring injuries
      are standard procedures in the treatment of hemodynamically stable patients with
      (Type C) pelvic injuries. Our aim is to show that this type of treatment achieves
      excellent and good results. All patients were operated on using the method of
      open reduction and anterior plate fixation of sacroiliac complex as well as
      fixation of the pubic symphisis. We present a retrospective study of the results
      concerning the treatment of 19 patients with (Type C) unstable pelvic injuries.
      The average age of the patients was 43,21 years old. The final functional
      results, 2 years post-surgery according to the Majeed scoring system and the
      results were excellent in 11 (57.89%) and good in 8 (42.1%) patients. There were
      no bad results to report. Type C pelvic ring injuries are unstable and unless
      they are adequately treated, they can lead to permanent consequences. Surgical
      treatment that includes open reduction and stable internal fixation of the
      anterior and posterior pelvic ring complex leads to excellent and good results.
      The patients that were treated surgically by fixation of the anterior and
      posterior pelvic ring complex return to their everyday lives and work activities.

PMID- 24298740
TI  - [Minimally invasive treatment of bilateral femoral shaft fractures in polytrauma
      patient using selfdinamisibile internal fixator. A case report].
AB  - Proper timing and surgical method in management of femur fractures in polytrauma
      patients can greatly reduce the mortality, morbidity and disability. The aim of
      this paper is to present the treatment of bilateral femoral fractures in
      polytrauma patient with dominant chest trauma by selfdynamisable internal fixator
      Mitkovic (SIF) as a definitive method of fractures treatment. A 23 years old
      female was injured in a traffic accident. After resuscitation and treatment of
      the dominant chest injuries, surgical treatment of bilateral femur fractures
      performed on the fourth day after the injury. Length of surgery was 65 minutes.
      There was not blood substitution during the intervention and blood loss through
      the operative wounds drainage. There was no worsening of the pulmonary function
      after orthopaedic surgery. The patient discharged from hospital postoperative day
      ten. Postoperative follow-up was 9 months. The fractures healed with an excellent
      functional result. Application of selfdynamisable internal fixator (SIF) with
      minimally invasive technique for the treatment of bilateral femoral fractures in
      polytrauma patients is a good operative method because poses minimally additional
      operative trauma and provides excellent biomechanical conditions for fracture
      healing.

PMID- 24298741
TI  - [Avascular necrosis of the femoral head in the patients with posterior wall
      acetabular fractures associated with dislocations of the hip].
AB  - INTRODUCTION: Acetabular fractures are severe injuries, mostly occured in young
      patients after traffic accident or fall from heights. Of the all acetabular
      fractures, posterior wall acetabular fractures are the most often observed.
      Regarding to mechanism of the injury, about 30% of these fractures are associated
      with posterior hip dislocation. MATERIAL AND METHODS: The incidence of AVN in 18
      patients with posterior wall acetabular fractures associated with dislocations of
      the hip is presented. Thompson-Epstein Scale (type I-V) was used as the
      classification of the injury. Kocher-Langenbeck surgical approach was achieved in
      all patients. RESULTS: Average following time after surgery was 22, 66 months (8
      36 months). After that period the incidence of femoral head AVN was observed in
      33.3%. Femoral head AVN was observed in 5.55% of patient who was treated by the
      reduction of hip dislocation in first 24 hours after injury, while in patients
      with later reduction, femoral head AVN were observed in 27.77%. CONCLUSION:
      Posterior wall acetabular fractures associated with hip dislocation are severe
      injuries. Urgent, closed reduction of the hip, early definitive stable
      osteosynthesis of acetabulum and the experience of surgical team are factors that
      greatly decrease the possibility for AVN occurence. Later reduction, comminution
      of posterior wall of the acetabulum (Thompson- Epstein III et IV), impaction,
      chondral lesion of the femoral head and associated fractures of femoral head,
      increase the possibility for AVN occurence.

PMID- 24298742
TI  - [Results of the application of a new method of internal fixation of femoral neck
      fractures--self-tapping antirotation cannulated screws (SAF)].
AB  - INTRODUCTION: Femoral neck fractures are one of the most common fractures
      primarily the elderly, coupled with a high degree of morbidity and mortality. The
      treatment is applied a number of methods of internal fixation (multiple
      cannulated screws available, DHS system, cefalomedullary). At the Department of
      Orthopedics and Traumatology of Nis developed a new method of fixation of femoral
      neck fracture, which allows stable fixation of dislocated and nondislocated
      femoral neck fracture. Self-tapping antirotation fixation (SAF) using two
      cannulated screws to initial compression fractures intraoperative and
      postoperative dynamic linear compression of the fracture with early full support
      to the patient. MATERIAL AND METHODS: In the period between 2008 to 2012, 53
      patients treated for femoral neck fracture in the Clinic for orthopedic and
      traumatology, Clinical center in Nis, Serbia, by SAF (the self-tapping cannulated
      screws antirotation; ORTOKON doo Nis). All patients were followed up after
      surgery in a minimum period of 13 weeks (13-106 weeks). The outcome was evaluated
      on the basis of clinical and radiological signs of fracture healing and the
      Harris hip score of functional recovery of the patient. RESULTS: Of the total
      number of patients (53) treated with this method of fixation, 31 of them were
      females and 22 males, mean age 52.7 years (28-75 years). The average time of
      surgery was 36.4 minutes (19-70 minutes). During the postoperative follow-up of
      all patients (53) operated by this method, six patients were lost in the further
      postoperative monitoring, so that 47 patients remained for final evaluation. The
      total incidence of nonunion of femoral neck fracture after surgery this method
      was 6.4% (three patients). Shortening of the femoral neck after fixation by this
      method was recorded in 27 cases, and what amounted to an average of 2.8 mm (1, 2
      mm in nondislocated to 4.55 with dislocated fracture) and did not affect the
      functional outcome. During radiographic follow-up was not detected fracture
      implants. CONCLUSION: Self-tapping screws cannulated antirotation (SAF method)
      represent a reliable method of fixation of dislocated and nondislocated femoral
      neck fracture. The main prerequisite for the proper healing of femoral neck
      fractures with this method is that anatomical fracture reduction is achieved by a
      closed or open method. This way of fixation allows the early full weight bearing
      patient operated limb and faster postoperative functional recovery of the
      fracture healing in optimal time.

PMID- 24298743
TI  - [Comparative analysis of the position of the graft in the femur after anterior
      cruciate ligament reconstruction done through the front inner portal and through
      the shin bone].
AB  - Anterior cruciate ligament (ACL) is the most common surgically treated knee
      ligament. If we take into account the fact that incidence of ACL injuries is
      growing, it is clearly that the interest of orthopedic surgeons for this
      pathology is also growing. Increasing number of this operations leads to
      increasing of complications, which requires its analysis. One of the most common
      failure of ACL reconstruction is a bad position of the graft in the femoral
      condyle. This study aimed to analyze the positioning of the graft in to the femur
      by two generally accepted techniques--transtibial technique and technique through
      the antero-medial portal. The analysis included postoperative radiographs in 60
      patients, of whom 30 were operated by transtibial technique and 30 by technique
      through anteromedial portal. Radiographic analysis involved the measurement of
      the AP digital imaging, the tunnel projection X ray measurements and measurements
      of the computed tomography (CT), which was here a control method. The accuracy of
      measurement was set at 0.5 degrees or 1 min. All radiographs were made in the
      same way according to the literature. The results showed that the neoligaments
      were placed lower in the femoral condyle by technique through anteromedial portal
      than by transtibial technique, and the difference was statistically significant
      (on tunnel X ray by anteromedial portal screws were average placed at 50.0
      degrees and 10:20 am, and by transtibial technique at 37.5 degrees or 10:45 am).
      Based on the results, it was concluded that the neoligaments were positioned
      closer to its anatomical position by technique through anteromedial portal.

PMID- 24298744
TI  - [Dynamic forces of Mitkovic self-dinamysible trochanteric Internal fixators
      (SIF)].
AB  - Dynamic trochanteric fractures implants allow fracture fragments to be
      compressed. Dynamisation can be realized if the axial pin force overcome friction
      force between pin and body of the implant. Examination of sliding iniciation
      forces in Mitkovic Selfdinamysible Trochanteric Internal Fixator (SIF). SIF was
      attached for angle block in the position with vertical orientation of pins. The
      transversal load of 5 kg was connected to pins by a rope. A dynamometer was used
      to measure force during the movement of angle block in up direction. Regression
      coefficients were a1 = 4,052 i b1 = 0,623 for SIF with 2 sliding screws with
      diameter of 7mm and a2 = 4,534 i b2 = 0,422 for SIF with 1 screw with diameter of
      10 mm. Coefficients of determination were: r12 = 0,470 and r22 = 0,123. Sliding
      of SIF pins can be achieved for each analysed body weight of patient (50-130 kg).
      Early bearing of operated leg is significant for sliding initiation of SIF
      sliding screws.

PMID- 24298745
TI  - [Stability and quality of osteosynthesis in treatment of tibial pylon fractures
      with dynamic external fixation typ Mitkovic].
AB  - The study included 35 patients with fractures of distal tibia treated at the
      department of orthopedics HC K. Mitrovica and the Orthopedic clinic in CHC of Nis
      by a dynamic external fixator fixation of ancle. Ovadia-Beals score was used to
      assess the quality and repositioning and to assess the stability assessment made
      osteosynthesis. The final functional result of treatment the patient was
      determined based on the AOFAS score. Deviations for postoperative talocrural
      angle for extraarticular fractures was approximately 6 degrees (excellent
      result). Student's T-test showed statistically significant difference (t = 1.693
      p < 0.05) before and after surgery in favor of a postoperative series in the
      analysis of articular fractures by Ovadia-Beals score, and that means much better
      anatomical conditions for healing. Student's T-test were not found statistically
      significant differences in postoperative radiographic parameters in postoperative
      series and series before removing fixator for the extraarticular and intra
      articular fractures, for extraarticular fractures (t = 1.440, p > 0.05), and
      intrarticular fractures, (t = 1.234, p > 0.05), which is a remarkable result and
      describes the remarkable stability of the fracture zone by this method.
      Distribution of complications: soft-tissue complications of 11.4%, healing in a
      bad position of 5.7%, nonunions 3%, infection 6%. Distribution of functional
      results according to AOFAS score: excellent 27.2%, good 40%, satisfactory 11.4%
      11.4% bad. Pearson's test (r = - 0.6002) has been shown that the weight of the
      fracture is correlated with the AOFAS score, or the level of the outcome of
      treatment decreases with the increase cominution of fracture zone. CONCLUSIONS:
      The lack of clear protocols in the literature; the method of dynamic external
      fixator fixation provides optimal biochemical conditions for the healing of these
      injuries; the final functional outcome of this series and the distribution and
      number of complications corresponding to the current data in the literature.

PMID- 24298746
TI  - Fractures of the scaphoid, diagnosis and management--a review.
AB  - The scaphoid is vitally important for the proper mechanics of wrist function.
      Fracture of the scaphoid bone is the most common carpal fracture. Among all wrist
      injuries the incidence of scaphoid fracture is second only to fractures of the
      distal radius. Scaphoid fractures are significant because a delay in diagnosis
      can lead to a variety of adverse outcomes that include nonunion, delayed union,
      decreased grips strength, range of motion and osteoarthritis of the radiocarpal
      joint. To avoid missing this diagnosis, a high index of suspicion and a through
      history and physical examination are necessary, because initial radiographs are
      often negative. Regardless of the technique of bone grafting, there will almost
      always be some loss of motion even if the fracture unites.

PMID- 24298747
TI  - [Knee angular deformity correction using unicorticotomy and callus distraction by
      external fixation method and presentation of new external fixation device for
      varus correction of proximal tibia].
AB  - The main goal of this paper is to present clinical results of surgical correction
      of angular (varus and valgus) deformities of knee area. Goal is also to present
      new external fixation device for surgical treatment of varus deformity of
      proximal tibia. As material it has been used series of 70 patients treated during
      the period of 6.5 years in University Orthopaedic and traumatology clinic.
      Biomechanical investigation of 80% cut bone model fixed by new external fixation
      device was performed in the measurement laboratory of Mechanical Faculty
      University of Nis. Clinical results of treatment of 58 high tibial surgeries (49
      varus and 9 valgus) and 12 distal femur surgeries (2 varus and 10 valgus) showed
      that unicorticotomy and callus distraction by the use of Mitkovic external
      fixation device leaded to correction and bone union. Superficial pin tract
      infection happened in 9 patients and has been successfully treated without pins
      removal. Biomechanical investigation of new device showed that during axial
      loading of bone model by 690 N (70 kg) movement of medial distal end of bone
      model was 0.30 mm while posterior distal end of bone model was 0.26 mm. From
      results obtained in can be concluded that unicorticotomy and gradual callus
      distraction by the use of external fixation is one reliable method. Biomechanical
      testing of new external fixation device showed that it is more stable in control
      of varus and posterior position of proximal tibial fragment.

PMID- 24298748
TI  - [Designing special prosthesis "spacer"].
AB  - Malignant diseases of the medial part of the femur, humerus and tibia, treated
      with surgical removal of the affected part of the bone and prosthesis fitting
      special "Spacer". This type of prosthesis is made in the form of the proximal and
      distal components that connect by screws. The design of endoprosthesis provides
      without possible rotation linear relationship and allows the transfer of load
      from the proximal to the distal bone, but the screws that provide connection are
      not exposed to stress. For pro-per sizing and implementation of a special
      prosthesis is necessary to determine the geometric parameters of bone mass and
      disease and then develop a computer model of the prosthesis. Designing a special
      prosthesis "spacer" is a complex procedure based on the processing of diagnostic
      images (X-ray, CT or MRI) with the use of specialized software digitized picture
      elements pixels translate into voxels. In this way a geometric model contains a
      form of external (KORTEX), and the internal geometry of the bone (medullary
      canal). On the basis of such a developed computer models is possible accurately
      determine the part of the bone that is necessary to remove, and the size of
      medullary canal space that is built into proximal or distal component of special
      endoprosthesis "Spacer".

PMID- 24298749
TI  - Genitourinary injuries associated with pelvic fractures.
AB  - INTRODUCTION: Pelvic fractures represent approximately 3% of all skeletal
      injuries. About 15% of patients with pelvic fractures have associated bladder or
      urethral injuries. The most common causes of pelvic fracture are motor vehicle
      accidents, motorcycle crashes, motor vehicles striking pedestrians, and falls.
      MATERIAL AND METHODS: Retrospective study included the patients treated in the
      Emergency Center, Clinical Center of Serbia, Belgrade, between 2000 and 2009. Of
      7445 patients, there were 894 injuries of the urinary tract and 376 pelvic
      fractures; 55 patients with pelvic fractures (14.6%) had bladder or urethral
      injuries. There were 31 patients with bladder injuries, 22 patients with urethral
      injuries, and two patients with associated injuries of the posterior urethra and
      the bladder neck. RESULTS: The bladder injuries were treated by surgical
      exploration, cystostomy, suture of the bladder lesions and urethral
      catheterization. Urethral injuries were treated by primary cystostomy and
      urethral reconstruction and catheterization in 18 patients (82%), while cystofix
      cystostomy was performed in four patients (18%). DISCUSSION: Genitourinary
      injuries increase overall mortality in patients with pelvic fracture, compared
      with traumas without associated GU injuries. These patients require
      multidisciplinary approach, preferably in tertiary institutions.

PMID- 24298750
TI  - Centers for Medicare and Medicaid Services--new interpretative guidelines for the
      conditions of participation for discharge planning--part 2.
AB  - The Conditions of Participation for Discharge Planning are the case manager's
      guide as to how to correctly develop, implement and re-assess a hospital
      discharge planning program. Virtually any questions you may have as to how to
      conduct the discharge planning process can be found in the CoP. As case managers,
      we should never have to guess as to what the "right thing" is to do as it relates
      to discharge planning. Referring to the CoP any time a question comes up will
      always lead you in the right direction.

PMID- 24298751
TI  - Preface. Adolescent psychopharmacology update.

PMID- 24298753
TI  - Pediatric psychopharmacology in primary care: a conceptual framework.
AB  - In a 2009 policy statement focused on children's mental health, the American
      Academy of Pediatrics recommended that pediatric primary care physicians achieve
      competence in initiating care for children with attention-deficit/hyperactivity
      disorder (ADHD), anxiety, depression, and substance use/abuse. Because treatment
      for 3 of these conditions--ADHD, anxiety, and depression--may, under certain
      conditions, include medication, the primary purpose of this article is to offer
      guidance to assist primary care physicians in decision-making about their use of
      psychotropic medications for these conditions. A few medications with proven
      efficacy and safety are emphasized. Secondarily, other medications that may be
      useful for other disorders are noted.

PMID- 24298752
TI  - Principles of psychopharmacology for the adolescent patient.
AB  - Physicians are presented with great challenges when attempting to integrate
      information from multiple sources, often with conflicting recommendations, to
      meet the present and future needs of adolescents and the expectations of their
      families and caregivers. For this reason, this article attempts to outline a
      general strategy in assessment and use of information. General history of
      presenting symptoms, results of examination details, and additional history from
      family or other contexts lead to the development of a reasoned hypothesis. The
      working hypothesis is the basis for subsequent treatment. Revisiting the ongoing
      data, including response to therapeutic intervention, leads to revised hypotheses
      that provide the basis for the new treatment formulation. Patients and their
      families become informed self-advocates and partners in achieving improved
      outcomes.

PMID- 24298754
TI  - Pharmacotherapy of inattention and ADHD in adolescents.
AB  - This article reviews the current use of stimulants in adolescents. The evidence
      base for treatment of attention-deficit/hyperactivity disorder (ADHD) in
      adolescents is meager compared with that of ADHD in children, and much recent
      research of older populations with ADHD has been directed toward adults rather
      than adolescents. The structure of psychosocial treatment of ADHD differs across
      developmental ranges. For example, in children, treatment of ADHD uses direct
      behavior modification via parents and teachers. Treatment approaches then change
      toward contracting in adolescents (acknowledging the emerging independence common
      at this age) and toward self-management and coaching in adults. Medication for
      ADHD, however, does not substantially differ across developmental epochs. In
      supplementation of data, specifically on adolescence, much of our understanding
      of treating adolescents comes from upward or downward extension of the child and
      adult data. Symptomatic treatment (treatment for inattention, hyperactivity, or
      impulsive behavior) has always been a parallel approach to diagnostic and
      developmentally specific selection of treatment based on an incomplete
      literature. In recognition, this article assumes that inference from children or
      adults to adolescents, in the absence of adolescent-specific data, is commonplace
      and often confirmed with clinical experience. Such inferences, in the face of
      literature gaps, in no way obviate the need for continued research focused on
      adolescence.

PMID- 24298758
TI  - Considering biomedical/CAM treatments.
AB  - Complementary and alternative medicine (CAM) is widely used to treat children
      with psychiatric disorders. In this review, MedLine was searched for various
      biomedical/CAM treatments in combination with the key words "childre",
      "adolescents", "psychiatric disorders", and "complementary alternative medicine".
      The biomedical/CAM treatments most thoroughly researched were omega-3 fatty
      acids, melatonin, and memantine. Those with the fewest published studies were N
      acetylcysteine, vitamin B12, and oxytocin, although many biomedical/CAM
      treatments have no published studies. Although data are modest, there is evidence
      to suggest that biomedical/CAM treatments may be helpful for a subgroup of
      children with psychiatric disorders. Further research and more randomized,
      controlled trials in children are warranted.

PMID- 24298761
TI  - [Acupuncture for infantile diarrhea].

PMID- 24298759
TI  - Why adolescents use substances of abuse.
AB  - In summary, adolescent substance use is associated with a variety of risks. Using
      a nonjudgmental and collaborative approach to treating adolescent substance users
      can yield positive results. Motivational interviewing and the adolescent
      community reinforcement approach are evidence-based, nonpharmacologic treatments
      for teens with substance use disorders.

PMID- 24298756
TI  - Treatment of psychosis in children and adolescents: a review.
AB  - Recognition and treatment of psychosis in children remain challenging. This may
      be partly because of the subtle nature of prodromal features and partly because
      psychosis-like experiences are rather common in that a rich fantasy life is
      normative for developing children. Recent research suggests that only about 5% of
      patients with schizophrenia have an onset before age 15 years. To help with early
      recognition, an understanding of frequently used concepts and terms such as ultra
      high risk, attenuated symptoms, and clinical high risk for schizophrenia were
      reviewed as part of this article. During prodrome of schizophrenia, marked
      difficulties with emotions, cognition, motor skills, and socialization are seen.
      A careful workup of children in whom a psychotic process is suspected is
      warranted and may help with diagnostic clarification and likely treatment
      strategies. In treating a patient at ultra high risk, second-generation
      antipsychotics may reduce the severity of prodromal symptoms; however, high
      dropout rates and limited treatment adherence are significant concerns. Other
      helpful strategies may include treatment with selective serotonin reuptake
      inhibitors and omega-3 fatty acids and therapies such as cognitive-behavioral
      therapy. The most important aspect of the early treatment, however, may be
      working with a specialized multidisciplinary early psychosis treatment team that
      will address and support the individual and his or her family with academic
      needs, socialization, and other needs or components in a comprehensive manner.

PMID- 24298757
TI  - Bipolar disorder in adolescence.
AB  - Bipolar disorder is a serious psychiatric condition that may have onset in
      childhood. It is important for physicians to recognize the symptoms of bipolar
      disorder in children and adolescents in order to accurately diagnose this illness
      early in its course. Evidence regarding the efficacy of various treatments is
      necessary to guide the management of bipolar disorder in youth. For example,
      several medications commonly used for adults with bipolar disorder have not shown
      efficacy for children and adolescents with bipolar disorder. This article reviews
      the prevalence, diagnosis, course, and treatment of bipolar disorder in children
      and adolescents and provides physicians with information that will aid in
      diagnosis and treatment.

PMID- 24298755
TI  - Impulsivity, irritability, and depression: antidepressants.
AB  - Definitional and conceptual issues related to the symptoms of impulsivity,
      irritability, and depression are described. A brief overview of the relevant
      neurobiology of each symptom is then provided. General psychopharmacologic
      strategies to address these symptoms are explored. Finally, brief clinical
      vignettes are described along with specific pharmacologic information on commonly
      used agents.

PMID- 24298763
TI  - [Cases of postoperative pain of liver cancer after transcatheter arterial
      chemoembolization].

PMID- 24298762
TI  - [Asthma at acute attack stage treated with "Shao's five needling therapy": a
      multi-central randomized controlled study].
AB  - OBJECTIVE: To evaluate the clinical efficacy of asthma at acute attack stage
      treated with "Shao's five needling therapy". METHODS: The randomized controlled
      method was applied to divide 210 cases into an observation group and a control
      group, 105 cases in each one. In the observation group, "Shao's five needling
      therapy" [Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12)] and the combined
      therapy were adopted, including oxygen uptake, aerosol inhalation and oral
      administration of prednisone. In the control group, the oral administration of
      theophylline sustained release tablet and the combined therapy were applied. The
      treatment was continued for 7 days. The clinical symptoms and physical signs such
      as wheezing, cough, expectoration, chest stuffiness, wheezing rale and shortness
      of breath, as well as lung function indices such as forced expiratory volume one
      second (FEV1) and peak expiratory flow (PEF) were observed before and after
      treatment in the two groups. METHODS: In the observation group, 69 cases were
      cured clinically, 20 cases effective remarkably, 7 cases effective and 0 case
      failed. In the control group, 49 cases were cured clinically, 31 cases effective
      remarkably, 15 cases effective and 0 case failed. The difference in the efficacy
      was significant in comparison of the two groups (P < 0.05). The therapeutic
      effect in the observation group was better than that in the control group. The
      total score of the symptoms and physical signs, FEV1 and PEF after treatment were
      all improved significantly in the two groups (all P < 0.01). And the results in
      the observation group were better than those in the control group (all P < 0.01).
      CONCLUSION: "Shao's five needling therapy" achieves the significant efficacy on
      asthma at acute attack stage. It significantly relieves the symptoms and physical
      signs of the patients and improves lung functions. The effect is better than that
      of theophylline sustained release tablet.

PMID- 24298760
TI  - [Electroacupuncture for post-stroke urinary incontinence: a multi-center
      randomized controlled study].
AB  - OBJECTIVE: To evaluate the clinical efficacy of electroacupuncture(EA) for
      apoplectic urinary incontinence. METHODS: Two hundred and four cases of
      apoplectic urinary incontinence were randomized into an EA group (136 cases) and
      an indwelling catheter group (68 cases). The EA was applied at Qugu (CV 2),
      Zhongji (CV 3), Shuidao (ST 28), Qihai (CV 6) and Guanyuan (CV 4), etc. in the EA
      group,5 times a week. Indwelling catheter was applied in the indwelling catheter
      group at intervals of 2-4 hours, and periodic bladder irrigation along with
      bladder rehabilitation training were also given. The efficacies were evaluated
      after 4 weeks of treatment. Before and after treatment, the urination diary
      (including the interval of urination, nocturia frequency, urination difficulty,
      urinary incontinence severity), bladder capacity, patients' satisfaction of the
      two groups were observed and the efficacy was evaluated. RESULTS: The total
      effective rate was 96.2% (125/130) in the EA group, which was apparently superior
      to 87.5% (56/64) in the indwelling catheter group (P < 0.05); except for nocturia
      frequency in the indwelling catheter group, the total score and the subitem score
      in the urination diary were all improved significantly after treatment in both
      groups (all P < 0.001), which were more obvious in the EA group (P < 0.001, P <
      0.05); the patients' satisfaction and bladder capacity were all improved
      significantly after treatment in both groups (all P < 0.001), which were more
      obvious in the EA group (both P < 0.001). CONCLUSION: The EA has an obvious
      effect for apoplectic urinary incontinence in urinary incontinence alleviation
      and bladder capacity increase, which has better efficacy than indwelling catheter
      therapy.

PMID- 24298764
TI  - [Comparative study on the brain protection in patients of traumatic cerebral
      infarction treated with bloodletting at Jing-well points and semen coicis].
AB  - OBJECTIVE: To verify the effect of bloodletting therapy at Jing-well points and
      semen coicis on patients with traumatic cerebral infarction. METHODS: Ninety
      patients were randomized into a bloodletting therapy at Jing-well points group
      (bloodletting group), a semen coicis group and a comprehensive therapy group, 30
      cases in each one. The conventional basic medication was applied in all of the
      three groups. In the bloodletting group, the bloodletting therapy was done at
      twelve Jing-well points with three-edged needle, 3 drops of blood required at
      each one, three times a day. In the semen coicis group, the semen coicis
      preparation was applied via nasal feeding or oral administration, 90 g each day,
      three times a day. In the comprehensive therapy group, the bloodletting therapy
      at twelve Jing-well points and semen coicis preparation were used in combination
      and the methods were same as the above two groups. After 4 weeks of treatment,
      the efficacy was assessed with nerve function defectscale (NDS). Fugl-Meyer scale
      of the upper and lower limb function was used to evaluate the motor function of
      the affected limbs of the patients before and after treatment. RESULTS: The
      scores of Fugl-Meyer scale of the upper and lower limb function were increased
      apparently after treatment in the patients of every group (P < 0.01, P < 0.05).
      The score increase was much more obvious in the bloodletting group and the
      comprehensive therapy group as compared with the semen coicis group (all P <
      0.01). The result in the comprehensive therapy group was superior to the
      bloodletting group (all P < 0.05). The total effective rates of NDS in the
      comprehensive therapy group, bloodletting group and semen coicis group were 96.7%
      (29/30), 83.3% (25/30) and 76.7% (23/30) separately. The result in the
      comprehensive therapy group was higher apparently than those in the bloodletting
      group and semen coicis group separately (both P < 0.05). The result in the
      bloodletting group was better than that in the semen coicis group (P < 0.05).
      CONCLUSION: The bloodletting therapy at Jing-well points and semen coicis
      alleviate apparently nerve function defect, improve the motor function of the
      affected limbs and achieve the better efficacy.

PMID- 24298765
TI  - [Impacts of acupuncture at Jing-well points on the differentiated meridians and
      temple-three-needle therapy on P300 of patients with early vascular cognitive
      impairment].
AB  - OBJECTIVE: To observe the efficacy on post-stroke mild cognitive impairment (MCI)
      treated with acupuncture at Jing-well points on the differentiated meridians and
      temple-three-needle therapy. METHODS: Seventy-three of stroke patients were
      randomized into an acupuncture group (37 cases) and a conventional treatment
      group (36 cases). Twenty healthy aged people in physical examination were
      collected as a control group. In the acupuncture group, on the basis of the
      conventional treatment of internal medication, the acupuncture at Jing-well
      points on the differentiated meridians and temple-three-needle therapy were
      applied. In the conventional treatment group, no any therapy was used except the
      conventional treatment of internal medication. In the control group, no any
      intervention was adopted. Neuroscan Nuamps electroencephalogram recording
      analysis system was used to determine the event-related potentials P300, and the
      amplitude and mini mental state examination (MMSE) score was observed before and
      after treatment in both groups. RESULTS: After treatment, in the acupuncture
      group, P300 latent stage was shortened, and the amplitude and the score of MMSE
      were increased (P < 0.05, P < 0.01). In the conventional treatment group, above
      indices were not changed obviously as compared with that before treatment (all P
      > 0.05). Compared with the conventional treatment group, the differences in P300
      latent stage, amplitude and MMSE score were remarkable in the acupuncture group
      (P < 0.05, P < 0.01). CONCLUSION: The acupuncture at Jing-well points on the
      differentiated meridians and temple-three-needle therapy improves the cognitive
      function of the patients with MCI.

PMID- 24298768
TI  - [Moxibustion at Back-shu points combined with auricular sticking therapy for 46
      cases of neurogenic urination in chindren].

PMID- 24298766
TI  - [Effect of penetrating needling at head acupoints on perennial allergic
      rhinitis].
AB  - OBJECTIVE: To evaluate the effects and safety of penetrating needling on head
      acupoints for perennial allergic rhinitis (PAR). METHODS: Eighty-one cases of PAR
      were randomly divided into an acupuncture group (41 cases) and a medication group
      (40 cases). Penetrating needling at head acupoints was adopted from Baihui (GV
      20) to Qianding (GV 21) and from Shangxing (GV 23) to Shenting (GV 24) in the
      acupuncture group. A to tal 4-week treatment was given to the patients with 3
      treatments a week. Loratadine tablet and azelastine hydrochloride nasal spray
      were given to the medication group continuously for 12 days. A follow-up was
      carried out 3 months after the treatment. The efficacy, symptom score and
      physical sign score, and side accidents were observed in both groups. RESULTS:
      The total effective rate was 95.1% (39/41) in the acupuncture group, which was
      better than 82.5% (33/40) in the medication group (P < 0.05). The total scores of
      clinical symptoms and each partial scores after the treatment, and total scores
      of clinical symptoms in follow-up were obviously decreased in both groups (all P
      < 0.01), the nasal obstruction score and the total scores of clinical symptoms in
      the acupuncture group were better than those in the medication group (P < 0.01, P
      < 0.05). Obvious side-effect had not been found during the treatment. CONCLUSION:
      Penetrating needling at head acupoints is a safe therapy for patients with PAR,
      and favorable effects can be found in both short term and long term.

PMID- 24298767
TI  - [Controlled research on multiple sclerosis treated with electroacupuncture and
      acupoint injection].
AB  - OBJECTIVE: To observe the clinical efficacy of multiple sclerosis (MS) treated
      with electroacupuncture and acupoint injection. METHODS: The block randomization
      method was used to divide 40 cases into an electroacupuncture (EA) group and an
      EA + acupoint injection (AI) group, 20 cases in each one. In the EA group, EA was
      used at corresponding Jiaji (EX-B 2), Weizhong (BL 40), Chengshan (BL 57), etc.
      In the EA + AI group, on the basis of EA, the acupoint injection of mouse nerve
      growth factor was supplemented. The activity of daily life (ADL) and expanded
      disability status score (EDSS) were observed in the two groups before and after
      treatment for the evaluation of the efficacy. RESULTS: The efficacy was achieved
      on MS after treatment in both groups (P < 0.01). After treatment, the scores of
      EDSS and Barthel index were (3.01 +/- 1.31) and (83.11 +/- 8.45) in the EA + AI
      group, which were better than those of (4.23 +/- 1.21) and (75.25 +/- 6.25) in
      the EA group (both P < 0.01). CONCLUSION: EA and AI co-act on reducing disability
      and improving the life quality in the treatment of MS and have achieved
      coordinately the significant effects.

PMID- 24298769
TI  - [Acupuncture combined with acupoint injection with syndrome differentiation for
      49 cases of chloasma].

PMID- 24298770
TI  - [Exploration on eye needling manipulation].
AB  - The 40-year experiences in the clinical application of eye acupuncture in our
      hospital are summarized. The manipulation of needle insertion, withdrawal and
      puncture procedure is analyzed. The keys of the techniques of eye acupuncture are
      explained. The basic needling manipulations are determined. In the insertion of
      needle, professor Peng stressed on the stability, accuracy and fast, without
      lifting, thrusting, rotating, and opening/closing techniques involved. TIAN Wei
      zhu emphasizes the gentle insertion, pain avoiding, apparent needling sensation
      and needling sensation transmission. In terms of acupuncture operation, skin
      stretching, patient's attention shifting, quick insertion of needle and slow-down
      moving of needle body are required. The outside orbit transverse needling method
      is recommended basically.

PMID- 24298771
TI  - [Auricular point sticking for 86 cases of Tourette syndrome in children].

PMID- 24298772
TI  - [Exploration on the application characteristics of bloodletting therapy for the
      diseases relevant with soft tissue infection by data mining technology].
AB  - OBJECTIVE: Using the data mining technology to analyze the application law of
      bloodletting therapy for the diseases relevant with soft tissue infection and
      explore the effect specificity of bloodletting therapy. METHODS: The variety of
      diseases treated with bloodletting therapy was taken as the sample data by
      collecting the reports from the periodical literatures. The network database of
      bloodletting literature was set up. The association rule of data mining
      technology was adopted to extract the information on the diseases relevant with
      soft tissue infection in the periodical literatures. The frequency item of the
      superiority disease category was calculated. And the deep mining was done in
      terms of the needle device, point selection and the bleeding amount separately.
      The application law of bloodletting therapy was summarized in the treatment of
      the diseases relevant with soft tissue infection. RESULTS: Fourteen kinds of
      relevant diseases of soft tissue infection treated with bloodletting therapy were
      included in the contemporary periodical literatures, of which, the reported case
      number and the reporting frequency were the highest for hordeolum and breast
      abscess. The three-edged needle was used the most frequently in the manipulation.
      The acupoints selected were the local Ashi points, combined with the symptomatic
      acupoints. The bleeding amount was not normalized by the ideas of different
      physicians. CONCLUSION: The bloodletting therapy achieves the better curative
      effect on some diseases relevant with soft tissue infection and this therapy
      deserves to be further promoted in clinical practice.

PMID- 24298773
TI  - [Manipulation and comprehensive application of reinforcing-reducing methods
      according to numbers and directions of rotation].
AB  - To trace to the source of the needling technique called "dragon and tiger
      warring" so as to bring its immediate effect of pain relieving into full play.
      Taking contents of Huangdi Neijiig (Yellow Emperor's Internal Classic), Nanjing
      (Classic of Questioning) and analyses of various schools in Zhenjiu Dacheng
      (Compendium of Acupuncture and Moxibustion) as references, thoughts of
      "principles of yin-yang inter-transformation", "yin-yang numbers of six and nine"
      as well as "the mysterious principles of reinforcing-reducing" in "dragon and
      tiger warring" technique are further studied. "Dragon and tiger warring"
      technique combined with "twirling reinforcing and reducing method according to
      clockwise or anticlockwise direction", "qi lifting method" and "theory of nine
      and six circles" can communicate the meridian qi exteriorly, interiorly, upper
      and lower. Taking professor ZHANG Jin's experiences on clinical application of
      "reinforcing and reducing according to number six and nine circles of rotation",
      the cores of reducing and reinforcing methods of "dragon and tiger warring",
      "back and forth method" as well as "qi lifting method" are applied
      comprehensively, so as to bring the immediate pain relieving effect of "dragon
      and tiger warring" technique into full play.

PMID- 24298774
TI  - [Analysis on two cases of clinical infection caused by fire needle therapy].

PMID- 24298775
TI  - [Acupuncture at ocular muscle points for 35 cases of trochlear nerve paralysis].

PMID- 24298776
TI  - [Sixteen cases of tremor syndrome treated with penetration needling method].

PMID- 24298777
TI  - [Effects of electroacupuncture on the expression of oxidized low-density
      lipoprotein and its receptors in rats with coronary atherosclerotic heart
      disease].
AB  - OBJECTIVE: To explore action mechanism of electroacupuncture for coronary
      atherosclerotic heart disease (CHD) in order to provide experimental support for
      clinical acupoint selection. METHODS: Among sixty clean-grade healthy male Wistar
      rats, twenty-four cases were randomly selected as a normal control group and an
      electroacupuncture (EA) preconditioning group, 12 cases in each one. Then rats in
      the EA preconditioning group and the rest 36 rats were fed with high fat diet for
      12 weeks to duplicate the CHD model. When the models were successfully
      established, the rats were randomly divided into a model control group, an EA
      group and a medication group, 12 cases in each one. EA was applied with Hwa-to
      SDZ-IV apparatus in the EA preconditioning group at "Neiguan" (PC 6) and "Xinshu"
      (BL 15), 1 mA in current intensity, 2 Hz in frequency, 30 min per times, once
      every other day for 14 weeks. When model was established, the same acupoint and
      method was used in the EA group for 2 weeks while intragastric administration of
      atorvastatin mixed suspension, 0.25 mg/kg, once a day, was applied in the
      medication group for 2 weeks. The content of oxidized low-density lipoprotein
      (oxLDL) in the serum was tested by double antibody enzyme-linked immunosorbent
      assay (ELISA) while content of lectin-like oxidized low density lipoprotein
      receptor-1 (LOX-1) in coronary arterial tissue was test by western blot method.
      Expression of LOX-1 mRNA was tested by fluorogenic quantitative polymerase chain
      reaction (PCR). RESULTS: After model was duplicated successfully, the content of
      oxLDL in the serum and the expression of LOX-1 and its mRNA in coronary arterial
      tissue in the model control group were increased significantly compared with
      those in the normal control group (all P < 0.01). Compared with the model control
      group, the content of oxLDL in the serum and the expression of LOX-1 and its mRNA
      in coronary arterial tissue in the EA preconditioning group, EA group and
      medication group were significantly reduced (all P < 0.01). CONCLUSION: The
      electroacupuncture at "Neiguan" (PC 6) and "Xinshu" (BL 15) could effectively
      reduce the content of oxLDL in the serum and expression of LOX-1 and its mRAN in
      coronary arterial tissue in CHD rats. The oxidative modificatory low-density
      lipoprotein and its specific receptor system could be one of the ways to
      prevention and treatment of acupuncture for CHD.

PMID- 24298778
TI  - [Effects of acupuncture on kidney morphological structure and expression of TGF
      beta1 mRNA in rats with spontaneous hypertension].
AB  - OBJECTIVE: To explore mechanism of acupuncture for renal interstitial fibrosis
      (RIF) in hypertension rats. METHODS: Twenty-four 24-week-old male spontaneously
      hypertensive rats were randomly divided into a model group, a perindopril group
      and an acupuncture group, eight cases in each one. In the acupuncture group, with
      rats tied up, electroacupuncture was applied at bilateral "Quchi" (LI 11) and
      "Zusanli" (ST 36) under mild vibration of needle handle for 20 min, once a day.
      In the perindopril group, perindopril (0.4 mg/kg) suspension liquid was applied
      for intragastric administration, once a day. In the model group, rats were tied
      up for 20 min a day without any treatment. Eight same-age same-race Wistar Kyoto
      (WKY) rats with normal blood pressure were taken as a control group, which was
      given with free diet but no treatment. The treatment was reuqired for six weeks.
      The systolic blood pressure of caudal artery was tested. Kidney morphological
      structure was observed by HE coloration. Deposition optical density of type I and
      III collagen in kidney was tested by immunohistochemistry. Expression of
      transforming growth factor-beta1 (TGF-beta1) mRNA was tested by reverse
      transcription polymerase chain reaction (RT-PCR) method. RESULTS: Compared with
      the model group, the blood pressure was significantly decreased in the
      acupuncture group (P < 0.01), the damage of kidney morphology was minor, positive
      depositional area of type I and III collagen was obviously decreased (both P <
      0.05), and the expression of semi-quantitative analysis of TGF-beta1 mRNA was
      decreased (P < 0.05), which had similar effect as western medication perindopril.
      CONCLUSION: Acupuncture at "Quchi" (LI 11) and "Zusanli" (ST 36) probably
      intervenes the process of RIF by reducing synthesis of kidney type I , III
      collagen and restraining expression of TGF-beta1.

PMID- 24298779
TI  - [Observation on electroacupuncture at neimadian (extra) and neiguan (PC 6) for
      analgesia after thoracic surgery].
AB  - OBJECTIVE: To observe the effectiveness and safety of electroacupuncture (EA) at
      Neimadian (Extra) and Neiguan (PC 6) for analgesia after thoracic surgery.
      METHODS: One hundred and twenty cases of thoracic surgery were randomly divided
      into an electroacupuncture (EA) group (60 cases) and a medication group (60
      cases). EA was applied at Neimadian (Extra) and Neiguan (PC 6) for postoperation
      analgesia in the EA group, while patient-controlled intravenous analgesia (PCIA)
      was applied in the medication group. The score of visual analogue scale (VAS),
      analgesia effect, safety and beta-endorphin level after the treatment in both
      groups were compared. RESULTS: Compared with those before the treatment, the VAS
      scores in every time point after surgery were decreased (all P < 0.05), which
      were lower in the EA group (P < 0.01). The excellent and good rates were 96.7%
      (58/60) and 75.0% (45/60) seperately, the analgesia effect in the EA group (2 h
      after operation) was superior to that in the medication group (P < 0.01). The
      safety degree in EA group was higher to that in the medication group (P < 0.01).
      Compared with that before the treatment, the beta-endorphin level in two groups
      after treatment was both increased, which was higher in the EA group (P < 0.01).
      CONCLUSION: Electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) has better
      analgesia effect (2 h after operation) and safety than PICA on analgesia after
      thoracic surgery.

PMID- 24298780
TI  - [Internationalization and innovation of abdominal acupuncture].
AB  - Characteristics of abdominal acupuncture are analyzed through three aspects of
      inheriting and innovation, collaborated research as well as international visual
      field. It is pointed that abdominal acupuncture is based on clinical practice,
      focuses on enhancing the therapeutic effect and expending the clinical
      application. It also promots the thinking on how to recall the tradition and how
      to inherit tradition availably. The modern medical problems should be studied and
      innovation resolutions should be searched, which can help the
      internationalization and modernization of abdominal acupuncture.

PMID- 24298781
TI  - [The present-stage advantage diseases of abdominal acupuncture from reports of
      clinical randomized controlled trial].
AB  - The reports of clinical randomized controlled trial (RCT) that takes abdominal
      acupuncture as main treatment are arranged in order to summarize its advantage
      diseases at current stage. Up to May 1st, 2012, 107 reports that meet the
      inclusion criteria are collected by computer retrieval in CBM database, CNKI,
      VIP, Wan fang database, PubMed, Embase and manual retrieval in outdated issue
      database of Guangzhou University of CM. Diseases that has better efficacy by
      abdominal acupuncture are summarized. There are 38 kinds of present-stage
      advantage diseases of abdominal acupuncture, including internal medicine,
      surgery, gynaecology, pediatrics, orthopedics and dermatology, but those are far
      less than abdomen needle indications in the Abdominal Acupuncture Therapy written
      by Professor BO Zhi-yun. The doctors of abdominal acupuncture should not only pay
      attention to the application of RCT in clinical research to acquire high-quality
      reports, but also improve one's level of treatment and research of abdominal
      acupuncture to apply it into more specialist areas.

PMID- 24298782
TI  - [Application exploration of comparative effectiveness research in clinical
      efficacy optimization of abdominal acupuncture].
AB  - The concepts and characteristics of comparative effectiveness research (CER) are
      analyzed to explore its scientific research methodology in clinical efficacy
      optimization of abdominal acupuncture. The designs of CER focus on patients,
      which emphasize assessment of comprehensive efficacy in real medical environment
      instead of simple efficacy in randomized controlled trial (RCT). Its research
      strategy involves four categories and three subject, covering acquiring, saving
      and management, comparison and application of clinical evidence, which has
      practical application value in comprehensive comparison of advantages and
      efficacy rules of different acupuncture therapies and acupoint prescriptions. By
      establishing clinical registration system, oversized-sample data could be
      acquired from different centers to effectively overcome insufficient sample
      induced sampling error. It has important value in system summary and optimization
      of clinical efficacy of abdominal acupuncture. The CER fully illustrates clinical
      reality of acupuncture-moxibustion and provides strong support of scientific data
      for optimization of curative effect. It embodies prescription standardization,
      manipulation normalization and methodization of syndrome differentiation in
      clinic of abdominal acupuncture, which is expected to achieve evidence-based
      optimization of treatment prescription and technique in abdominal acupuncture.

PMID- 24298783
TI  - [Clinical efficacy observation on abdominal acupuncture for cyclomastopathy].
AB  - OBJECTIVE: To verify clinical efficacy of abdominal acupuncture for
      cyclomastopathy. METHODS: One hundred and twenty-one cases of cyclomastopathy
      were randomly divided into an abdominal acupuncture group (64 cases) and a
      routine treatment group (57 cases). In the abdominal acupuncture, basic treatment
      (including psychological counseling and Chinese patent medicine Rupixiao) and
      abdominal acupuncture at Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan
      (CV 4) and Huaroumen (ST 24) were applied at the same time. In the routine
      treatment group, only basic treatment was applied. Before and after the
      treatment, visual analogue scale (VAS) of main symptoms and WHO Quality of Life
      100BREF score were observed, also clinical efficacy of both groups was compared.
      RESULTS: The scores of VAS and WHO Quality of Life-100BREF in both groups had
      statistical significances before and after the treatment (both P < 0.05),
      indicating two treatments could both effectively relieve pain and improve life
      quality. The total effective rate was 84.4% (54/64) in the abdominal acupuncture
      group, which was superior to 68.4% (39/57) in the routine treatment group (P <
      0.01). The abdominal acupuncture had best effect for moderate pain (P < 0.05).
      CONCLUSION: The abdominal acupuncture could improve clinical symptoms and life
      quality of patients with cyclomastopathy.

PMID- 24298784
TI  - [Efficacy observation on abdominal acupuncture for adhesion-stage shoulder
      periarthritis].
AB  - OBJECTIVE: To evaluate the efficacy of abdominal acupuncture for adhesion-stage
      shoulder periarthritis. METHODS: One hundred and fifty-seven cases of shoulder
      periarthritis were randomly divided into an abdominal acupuncture group (79
      cases) and a body acupuncture group (78 cases). The abdominal acupuncture was
      applied at Zhongwan (CV 12), Shangqu (KI 17) and Huaroumen (ST 24) in the
      abdominal acupuncture group while conventional acupuncture was applied at Jianyu
      (LI 15), Jianliao (TE 14) and Jianzhen (SI 9) in the body acupuncture group. The
      treatment was given three times a week for both groups and ten times made an
      observation course. Before and after treatment, visual analogue scale (VAS) was
      adopted for pain assessment and functional activity score (Mallet score) was used
      for shoulder joint function assessment for all the patients. Also the efficacy of
      both groups was compared. RESULTS: The total effective rate in the abdominal
      acupuncture group was 92.4% (73/79), which was superior to 71.8% (56/78) in the
      body acupuncture group. The score of VAS after the treatment was 2.58 +/- 1.64 in
      the abdominal acupuncture group while 3.12 +/- 1.93 in the body acupuncture
      group, which had no statistical significance between each other (P > 0.05). The
      functional activity score after the treatment was 8.34 +/- 3.02 in the abdominal
      acupuncture group while 7.49 +/- 3.36 in the body acupuncture group, which had no
      statistical significance between each other (P > 0.05). CONCLUSION: The abdominal
      acupuncture is an ideal treatment for adhesion-stage shoulder periarthritis,
      which has better total efficacy than conventional acupuncture. It achieves the
      same effect in relieving pain and improving functional activity as conventional
      acupuncture, but also has an advantage at fast selection of acupoint and less
      discomfort of needling sensation.

PMID- 24298785
TI  - [Case of erythermalgia].

PMID- 24298786
TI  - [Experiences of Sun's acupuncture in treating emergencies].
AB  - The Sun's acupuncture includes Sun's painless acupuncture technique, Sun's
      reinforcing-reducing method and Sun's hand-manipulating method. The key points of
      Sun's painless acupuncture method are summarized as one fast manipulation, two
      slow manipulations and finger pressure during needle insertion. While the key
      points of Sun's reinforcing-reducing process refers to needle insertion firstly,
      twisting secondly and followed by scraping the handle of the needle. The contents
      of Sun's hand-manipulating method includes short hand-manipulating, continuous
      hand-manipulating and intermittent hand-manipulating. There are four
      characteristics of Sun's reinforcing-reducing method. The first is dexterity and
      gentleness; the second is the combination of strong stimula tion and weak
      stimulation; the third characteristic is the requirement of the same manipulation
      rhythm during the whole needling process; and the fourth is to use different
      stimulus to distinguish reinforcing and reducing. Emergent cases treated with
      Sun's acupuncture method are also provided in this article for reader's
      references.

PMID- 24298787
TI  - [Case of recurrent thyroid adenoma].

PMID- 24298788
TI  - [Quality improvement on acupuncture intervention report: application and
      perfection of STRICTA].
AB  - ABSTRACT Clinical application of standards for reporting interventions in
      clinical trials of acupuncture (STRICTA) is introduced in this article, and
      improving opinions are proposed as well. STRICTA has already been extensively
      applied in designation of acupuncture clinical trials, composition of articles
      and quality assessment of acupuncture literature. According to the present
      version of STRICTA, it is suggested that items such as "standards and methods on
      acupoint selection and location", "angle and direction of needle insertion" and
      "whether the subjects ever have been acupunctured" should be further perfected.
      Individuated treat protocols which is highlighted on treatment according to
      differentiation of syndromes according to different opportunities and stages of
      diseases should be promoted so as to give better expression to the
      characteristics of Chinese medicine and enhance the clinical value of the
      relative literature.

PMID- 24298789
TI  - [Anti-inflammatory: effect mechanism of warming-dredging in moxibustion].
AB  - The universality of anti-inflammation in moxibustion is analyzed in this article
      from its adaptation disease and ancient documentary records. The specificity of
      anti-inflammation in moxibustion is pointed out from its disease series research
      and scientific fact that moxibustion could be used for heat syndrome. The
      integrity of anti-inflammation in moxibustion is explained by series research
      result that four basic circulations of moxibustion for chronic inflammation are
      all effective. The two-way characteristic of moxibustion anti-inflammation is
      explained from the fact that moxibustion has regulation function both for excess
      and insufficiency of inflammation to demonstrate the effect mechanism of warming
      dredging in moxibustion lies in its anti-inflammation. At last, the relevant
      possible mechanism between moxibustion anti-inflammation and transient receptor
      potential vanilloid (TRPV) is proposed. The effect mechanism of warming-dredging
      in moxibustion lies in anti-inflammation, which could provide theoretic basis for
      prevention and treatment of moxibustion for serious diseases.

PMID- 24298790
TI  - [Comparative study of the diagnostic values of radio visio graphy, cone-beam
      computed tomography, and transparent teeth in the in vitro diagnosis of the first
      molar root canal system].
AB  - OBJECTIVE: To compare and analyze the performances of radio visio graphy (RVG),
      cone-beam computed tomography (CBCT), and transparent teeth in diagnosing the
      first molar root canal system in vitro; to provide an anatomical image of the
      first molar root canal therapy and analyze the relationship between the first
      molar root canal image and root canal anatomy. METHODS: A total of 269 extracted
      first molars were examined by RVG and CBCT in the mesiodistal and buccolingual
      sections. Transparent teeth were then constructed using dying root canals. The
      root canal system and the communicating branches between the pipes of the coronal
      2/3 and apical 1/3 areas of each root canal were displayed using RVG, CBCT, and
      transparent teeth. The performance of CBCT in the diagnosis was evaluated.
      RESULTS: The display rate of the first molar root (coronal 2/3) was 96.55% in
      CBCT. A significant difference was found between CBCT and the transparent teeth
      in the apical 1/3 area of the first molars (P < 0.05). The shapes of the mesial
      roots of the mandibular and maxillary first molars exhibited significant
      variance. The incidence rates of double and multiroot canals and pipe transport
      were high. CONCLUSION: CBCT and transparent teeth exhibit nearly equal
      performance in displaying the coronal 2/3 area of the root canal system. However,
      the performance of transparent teeth in displaying the apical 1/3 area is higher
      than that of CBCT. Meanwhile, the RVG-provided display of the multiroot canal and
      bifurcate root canals is limited. The incidence rates of double or multiroot
      canals and pipe transport in the mesial roots of the mandibular and maxillary
      first molars are high. CBCT has numerous advantages in displaying the root canal;
      it is also the most reliable method for diagnosing root diseases without trauma.

PMID- 24298791
TI  - [Establishment of animal model of rectus abdominis musculoperitoneal flap to
      reconstruct tongue defect].
AB  - OBJECTIVE: This study aims to investigate the feasibility of tongue
      reconstruction by a rectus abdominis musculoperitoneal flap with neurovascular
      pedicled in a canine model. METHODS: Twelve Beagle dogs were enrolled to the
      experiment. The animals were randomly divided into thee groups, two of which
      (group A and B) had nerve anastomosis. The left sides were experimental sides,
      whereas the right sides were control sides. Twelve weeks after operation,
      electrophysiological test was performed to detect hypoglossal nerve latency
      amplitude and conduction velocity as well as to evaluate the reinnervation of the
      rectus abdominis musculoperitoneal flap. RESULTS: Among the 12 Beagle dogs, nine
      animal tongue reconstruction models by rectus abdominis musculoperitoneal flap
      with neurovascular pedicled were successful, whereas one male Beagle dog died
      from ventral hemia 3 d after the operation, two female rectus peritoneal flaps
      were abandoned because their arterial anatomy differed from the male, which was
      not ideal. Hypoglossal nerve conduction velocity of group A and B were restored
      to the normal side of the 40%, 30%. CONCLUSION: Animal models of tongue
      reconstruction can be established by a rectus abdominis musculoperitoneal flap
      with neurovascular pedicled in Beagle dogs. Denervated rectus abdominis
      musculoperitoneal flap can regain hypoglossal nerve innervation. Hypoglossal
      nerve functions partly recover.

PMID- 24298792
TI  - [Effect of an arginine-containing polishing paste on Streptococcus mutans
      adhesion to exposed dentin surfaces].
AB  - OBJECTIVE: To evaluate the effect of an arginine-containing antihypersensitivity
      polishing paste on Streptococcus mutans (S. mutans) adhesion to treated dentin.
      METHODS: Dentin discs were treated with acid to expose dentin tubules, and then
      polished with either pumice or a polishing paste containing arginine. The surface
      roughness of the treated dentin was measured. The effects of dentin treatment on
      S. mutans adhesion and glucosyltransferase (GTFs) gene expression were also
      evaluated. RESULTS: The surface roughness decreased after polishing with both
      pumice and arginine-containing polishing paste. Moreover, the polishing paste
      affected gtfB and gtfC expressions. CONCLUSION: The arginine-containing polishing
      paste affects S. mutans adhesion, as well as gtfB and gtfC expressions. The
      polishing paste may be used to prevent caries in exposed dentin areas.

PMID- 24298793
TI  - [Three-dimensional finite-element analysis of maxillary protraction based on
      labiolingual appliance].
AB  - OBJECTIVE: This study aims to analyze the biomechanical effects of four sutures
      that are related to maxillary growth during a maxillary protraction treatment
      cycle based on labiolingual appliance. METHODS: A three-dimensional simulation of
      labiolingual appliance was performed based on a three-dimensional finite-element
      maxillofacial model combined with solid-modeled sutures. RESULTS: The
      displacement and stress distributions were calculated. The labiolingual appliance
      was suitable for patients with underbites or deep overbites. Sutura
      frontomaxillaris and sutura zygomaticomaxillaris were vital to the forward
      displacement and counterclockwise rotation of the maxillary. The changes in
      sutura zygomaticotemporalis and sutura palatine were not significant. CONCLUSION:
      The influences of the labiolingual appliance on the sutures during the treatment
      cycle of maxillary protraction can be effectively simulated by the three
      dimensional finite-element maxillofacial model.

PMID- 24298794
TI  - [Periodontal treatment for cardiovascular risk factors: a systematic review].
AB  - OBJECTIVE: To evaluate the efficacy of periodontal treatment for the management
      of cardiovascular risk factors. METHODS: Eligible studies in Cochrane Controlled
      Trials Register/CENTRAL, PubMed, EMBASE, and China Biology Medicine disc
      (CBMdisc) were searched until October 13, 2011. References of the included
      studies were hand searched. Two reviewers assessed the risk of bias and extracted
      the data of the included studies in duplicate. Meta-analysis was conducted with
      Revman 5.1. RESULTS: Six randomized controlled trials involving 682 participants
      were included. One case had low risk of bias, another one had moderate risk of
      bias, and the remaining four had high risk of bias. Meta-analysis showed that
      periodontal treatment has no significant effect on C-reactive protein, total
      cholesterol, low-density lipoprotein cholesterol, and triglycerides (P > 0.05).
      However, the treatment had a significant effect on high-density lipoprotein
      cholesterol [MD = 0.05, 95% CI (0.00, 0.09), P = 0.04]. CONCLUSION: Periodontal
      treatment has good effects on controlling high-density lipoprotein cholesterol
      although more randomized controlled trials must be conducted to verify its
      effectiveness.

PMID- 24298795
TI  - [Microarc oxidation of titanium surfaces on osteoblast morphology and
      cytoskeleton].
AB  - OBJECTIVE: This study aimed to evaluate the effects of the microarc oxidation
      surface on cell morphology and cytoskeleton. METHODS: Pure titanium with a
      diameter of 15 mm and a thickness of 1 mm was divided into four groups: grooved
      surfaces (group G); sandblasted surfaces (group SB); grooved microarc oxidation
      surfaces (group GMAO); and sandblasted microarc oxidation surfaces (group SBMAO).
      Osteoblast cells were cultured in each group. The morphology and proliferation of
      the cells on the titanium surface were observed by scanning electron microscope
      (SEM). The cytoskeleton was evaluated by laser scanning confocal microscope
      (LSCM). RESULTS: The osteoblasts were inoculated after 12 h; these osteoblasts
      then spread along the surface of the titanium plate. In GMAO and SBMAO groups,
      the osteoblasts converged in the hole. The actin fibers in each group were
      clearly visible. In particular, the actin fibers in GMAO and SBMAO groups were
      arranged in parallel and formed bundles that extended into the holes. CONCLUSION:
      After microarc oxidation, the titanium surface significantly affected the
      morphology and cytoskeleton of osteoblasts.

PMID- 24298796
TI  - [Analysis of velopharyngeal morphology in operated cleft palate patients with
      levator veli palatini retropositioning according to Sommerlad].
AB  - OBJECTIVE: To study the relationship between velopharyngeal morphology and
      velopharyngeal function in operated cleft palate patients with velopharyngeal
      competence (VPC) with levator veli palatini retropositioning according to
      Sommerlad. METHODS: Three groups were included in the study. The experimental
      group comprised 18 incomplete cleft patients (group T1) repaired with VPC
      repaired with levator veli palatini retropositioning according to Sommerlad and
      14 incomplete cleft patients (group T2) with velopharyngeal incompetence (VPI)
      repaired with Langenbeck's technique. The control group was composed of 13 normal
      adults. The outcome of the velopharyngeal function by nasopharyngoscopy and
      lateral cephalogram was assessed. Skeletal landmarks and measurements were
      derived from the tracing of lateral cephalograms. The measurements included velar
      length, pharyngeal depth, and adequate ratio of velar length to pharyngeal depth.
      The cranial base, cervical vertebrae, posterior nasal spine, and the position of
      the posterior pharyngeal wall (PPW) in the pharyngeal triangle were also
      analyzed. All data were subjected to student's t-test of statistical
      significance. RESULTS: All 18 subjects in group T1 obtained complete
      velopharyngeal closure. Velopharyngeal closure in seven, five, and two subjects
      in group T2 was 70%, 50% to 70%, and less than 50%, respectively, according to
      the results of nasopharyngoscopy. The lateral velar length (25.7 mm + 2.3 mm) in
      group T1 was similar to that of the control group (29.9 mm + 2.7 mm) (P > 0.05).
      The pharyngeal depth in group T1 was shorter than that in the other two groups,
      and the adequate ratio (1.43 + 0.26) was similar to that in the normal group
      (1.45 + 0.26). Group T2 had a significantly short velar length (22.9 mm + 2.3 mm)
      and normal pharyngeal depth, resulting in a small length/depth ratio (0.95 +
      0.14) than that in group T1 and the control group. PPW in the pharyngeal triangle
      was positioned superiorly in group T2 compared with the control group.
      CONCLUSION: The velopharyngeal morphology of operated cleft palate patients with
      VPC with levator veli palatini retropositioning according to Sommerlad was found
      to be similar to that of the normal control group. VPI cleft palate patients are
      characterized by a shorter palate, smaller adequate ratio (< 1.0), slightly
      counterclockwise-rotated pharyngeal triangle, and superiorly positioned PPW.

PMID- 24298797
TI  - [A follow-up study on velopharyngeal airway condition post pharyngoplasty].
AB  - OBJECTIVE: To observe changes in velopharyngeal airway condition post
      pharyngoplasty. METHODS: Thirty-five patients underwent sphincter pharyngoplasty
      (SPP) or pharyngeal flap (PF). The follow-up period was approximately six months.
      Duration of velopharyngeal airway obstruction was recorded. RESULTS: Average
      obstruction duration was (42.8 +/- 32.4) d. No significant difference in
      obstruction duration was found between the SPP and PF groups. Twenty-eight
      patients complained of mouth and lip dryness. Thirty-four patients experienced
      snoring while sleeping. CONCLUSION: Average obstruction duration post
      pharyngoplasty is 42.8 d. Oral respiration and snoring are common complications.

PMID- 24298798
TI  - [Mandibular incisive canal by cone beam CT].
AB  - OBJECTIVE: This study was conducted to determine the three-dimensional structure,
      course, and adjacent structure of the mandibular incisive canal (MIC) to ensure
      safety of dental implantation by cone beam CT (CBCT). METHODS: The CBCT images of
      the bilateral mandibles of 80 patients were retrospectively studied. The
      diameters of the mandibular incisive canal and the location in the adjacent
      structure were determined, including the distances between the MIC and the buccal
      and lingual plates of the alveolar bone, the inferior border of the mandible and
      the tooth apex, and the horizontal plane of the mental foramen. RESULTS:
      Approximately 78.75% (63 cases) of the CBCT scans showed the presence of the MIC
      with a mean diameter of 1.21 mm +/- 0.29 mm. The distances from the canal to the
      inferior border of the mandible and to the tooth apex were 7.82 mm +/- 1.86 mm
      and 7.24 mm +/- 2.82 mm, respectively. The distances between the canal and the
      buccal plate as well as between the canal and the lingual plate of the alveolar
      bone were 3.80 mm +/- 1.37 mm and 4.45 mm +/- 1.34 mm, respectively. The distance
      from the canal to the horizontal plane of the mental foramen was 5.62 mm +/- 2.21
      mm. CONCLUSION: CBCT could clearly show the three-dimensional structure, course,
      and adjacent structure of the MIC. Therefore, this technique could provide
      guidance for dental implantation in clinical applications.

PMID- 24298799
TI  - [Clinical investigation of the positioning accuracy of acute pulpitis pain].
AB  - OBJECTIVE: This study aims to investigate the positioning accuracy of acute
      pulpitis pain and its possible factors. METHODS: The clinical symptoms and
      physical signs of 3 432 cases of acute pulpitis were recorded and analyzed by
      using questionnaire forms, which included age, gender, tooth position, infection
      origin, pain history, time of acute attack, duration and nature of pain, pain
      frequency, referred pain areas, percussion examination, temperature pulp test,
      pulp bleeding, and positioning accuracy. Univariate analysis and multivariate
      stepwise regression analysis were used for data processing. RESULTS: Pain
      location was accurately identified by 39.1% of the patients with acute pulpitis.
      Referred pain could reduce the positioning accuracy of pain (P < 0.05), whereas
      infection originating from the periodontium could raise it (P < 0.05). Other
      factors might not be directly related to positioning accuracy (P > 0.05).
      CONCLUSION: Some cases of acute pulpitis pain can be located accurately. Referred
      pain and periodontium infection origin are related to the positioning accuracy of
      acute pulpitis pain. The exact cause of this correlation needs further study.

PMID- 24298800
TI  - [Oral health status and its correlation with oral health knowledge among middle
      aged people in Dongxiang, Bonan, and Yugur].
AB  - OBJECTIVE: To provide basic data for the prevention of oral diseases in
      minorities by investigating the oral health status and behavior related to oral
      health knowledge of individuals aged 35 to 44 years in Dongxiang, Bonan, and
      Yugur. METHODS: The caries and periodontal health of 445 individuals aged 35 to
      44 years were examined according to the method and criterion prescribed by the
      World Health Organization and the Third National Oral Health Epidemiologic
      Investigation. A questionnaire survey on related oral health knowledge and
      behavior was conducted. RESULTS: The crown caries prevalence rate in Dongxiang,
      Baoan, and Yugur were 48.28%, 79.47%, and 67.11%, respectively; the root caries
      prevalence rates were 38.62%, 69.54%, and 42.95%, respectively. The rates of gum
      bleeding in Dongxiang, Bonan, and Yugur were 86.90%, 90.07%, and 65.77%,
      respectively. The rates of dental calculus in Dongxiang, Bonan, and Yugur were
      99.31%, 100.00%, 99.33%, respectively, and the rates of periodontal bags were
      68.97%, 67.55%, and 43.62%, respectively. Only 69.84% of the respondents brush
      their teeth every day; 94.90% of the respondents do not floss. Only 20.19% of the
      respondents contact a doctor for a toothache, and 42.23% of the respondents have
      never seen a dentist. CONCLUSION: Caries morbidity is high among the respondents
      aged 35 to 44 years from Dongxiang, Bonan, and Yugur. The periodontal health
      status and oral hygiene of the respondents are poor, and behavior related to oral
      health knowledge is insufficient. Thus, more attention must be provided to the
      prevention and control of caries and periodontal diseases among middle-aged
      people in the area.

PMID- 24298801
TI  - [Effects of three different root canal preparation techniques on endodontic
      interappointment pain among the elderly].
AB  - OBJECTIVE: To study the clinical effects of three different root canal
      preparations on endodontic interappointment pain (EIAP) among the elderly.
      METHODS: In this study, 292 teeth with acute or chronic pulpitis or apical
      periodontitis were collected from 265 individuals. The samples were divided
      randomly into three groups. Three root canal preparations were utilized for
      groups M, G, and H. Modified single length technique with Mtwo instrument was
      utilized in group M. Modified step-back technique with Gates-Glidden bur was
      employed in group G, and step-back technique with stainless steel H-files was
      employed in group H. The EIAP rates were observed and compared. RESULTS: The
      rates of EIAP for groups M, G, and H were 5.81%, 6.38%, and 19.64%, respectively.
      A significant difference was observed between groups M and H (P < 0.012 5) as
      well as between groups G and H. However, no significant differences were observed
      between groups M and G (P > 0.012 5). CONCLUSION: Modified single length
      technique with Mtwo instrument and modified step-back technique with Gates
      Glidden bur can reduce EIAP in the elderly.

PMID- 24298802
TI  - [Influence on microstructure of dental zirconia ceramics prepared by two-step
      sintering].
AB  - OBJECTIVE: To investigate the microstructure of dental zirconia ceramics prepared
      by two-step sintering. METHODS: Nanostructured zirconia powder was dry compacted,
      cold isostatic pressed, and pre-sintered. The pre-sintered discs were cut
      processed into samples. Conventional sintering, single-step sintering, and two
      step sintering were carried out, and density and grain size of the samples were
      measured. Afterward, T1 and/or T2 of two-step sintering ranges were measured.
      Effects on microstructure of different routes, which consisted of two-step
      sintering and conventional sintering were discussed. The influence of T1 and/or
      T2 on density and grain size were analyzed as well. RESULTS: The range of T1 was
      between 1450 degrees C and 1550 degrees C, and the range of T2 was between 1250
      degrees C and 1350 degrees C. Compared with conventional sintering, finer
      microstructure of higher density and smaller grain could be obtained by two-step
      sintering. Grain growth was dependent on T1, whereas density was not much related
      with T1. However, density was dependent on T2, and grain size was minimally
      influenced. CONCLUSION: Two-step sintering could ensure a sintering body with
      high density and small grain, which is good for optimizing the microstructure of
      dental zirconia ceramics.

PMID- 24298803
TI  - [Effects of a zirconia primer and a self-adhesive resin cement on zirconia
      bonding].
AB  - OBJECTIVE: To evaluate the effects of a zirconia primer and a self-adhesive resin
      cement on the resin bonding zirconia. METHODS: Eighty zirconia blocks were
      manufactured, alumina-sandblasted, and randomly divided into five groups that
      received surface-treatments using different resin cements: group C, treated with
      a conventional bisphenol-A diglycidyl dimethacrylate (Bis-GMA)-based resin
      cement; group R, treated with a self-adhesive resin cement; group S, silica
      coated via a Sol-gel process, conditioned with silane, and then treated with the
      Bis-GMA-based resin cement; group ZC, conditioned with a zirconia primer (Z-Prime
      Plus) and subsequently treated with the Bis-GMA-based resin cement; group ZR,
      conditioned with the zirconia primer and treated with the self-adhesive resin
      cement. Light-cured composite resin cylinders were prepared and bonded on the
      prepared zirconia blocks. Half of the specimens in each group were water-stored
      for 24 hours, whereas the remaining specimens were aged by thermocycling. All
      specimens were then subjected to shear bond strength (SBS) testing. Fourier
      transmission infrared (FT-IR) spectroscopy and gas chromatography-mass
      spectrometry (MS) were performed to characterize the zirconia primer. RESULTS:
      Group C presented the lowest SBS, whereas groups R, ZC, and ZR presented the
      highest values. Thermocycling had no effect on SBS. FT-IR results showed that Z
      Prime Plus contained a benzene ring and a carbonyl group. MS analysis showed that
      Z-Prime Plus contained 2-hydroxyethyl methacrylate, triethylamine. CONCLUSION:
      Zirconia primer and self-adhesive resin cement increase the resin bonding of
      zirconia.

PMID- 24298804
TI  - [Effects of periodontal mechanical therapy with local and systemic drugs on
      carotid artery and serum high-sensitivity C-reactive protein in rats with chronic
      periodontitis associated with atherosclerosis].
AB  - OBJECTIVE: The aim of this study is to investigate the effects of serum high
      sensitivity C-reactive protein (hsCRP) and the pathological changes in the
      carotid artery after periodontal mechanical therapy with local and systemic drugs
      in SD rats with chronic periodontitis (CP) associated with atherosclerosis (As).
      METHODS: Thirty-five SD rats were randomly divided into two groups: control group
      (group A) and CP+As group (group B). Group B was further divided into the natural
      process group (B1), the periodontal mechanical treatment group (B2), the
      periodontal mechanical treatment plus local drugs group (B3), and the periodontal
      mechanical treatment plus local and systemic drugs group (B4). Each group
      comprised seven rats. Serum hsCRP levels were evaluated at baseline 1 week after
      the first periodontal therapy and 1, 3, and 5 weeks after the second periodontal
      therapy by enzyme linked immunosorbent assay (ELISA). The pathological lesion in
      the carotid artery plaque was stained with hematine and eosin. RESULTS: The
      levels of serum hsCRP in group B1 increased gradually as time passed and became
      significantly higher than that of the other groups five weeks after periodontal
      therapy (P < 0.001). The levels of serum hsCRP in groups B2, B3, and B4 increased
      gradually and reached the peak 1 week after the second periodontal therapy. After
      that, the levels of serum hsCRP decreased gradually but were still higher than
      that of group A (P < 0.05). The levels of serum hsCRP in groups B3 and B4 were
      significantly lower than that in group B2 3 and 5 weeks after the second
      periodontal therapy (P < 0.001). Histologic sections revealed increased foam cell
      infiltration and disordered and destructed elastic fibers in groups B1 and B2.
      The thickness of the blood vessels in groups B3 and B4 was more uniform than that
      in groups B1 and B2. The elastic fibers in groups B3 and B4 were lined up in
      order. CONCLUSION: Direct periodontal mechanical treatment results in acute,
      short-term, systemic inflammation and might increase the risk of atherosclerosis
      in SD rats. However, the levels of serum hsCRP decreased gradually 3 to 5 weeks
      after therapy. With periodontal mechanical treatment, the benefits of local and
      systemic drugs are associated with improvement in atherosclerotic lesion
      progression.

PMID- 24298805
TI  - [Histopathological study on the healing of orthodontic implant-bone interface
      adjacent to extraction].
AB  - OBJECTIVE: Osseointegration of orthodontic microscrew implant is influenced by
      tooth extraction. This study aims to evaluate the safety margin of the
      osseointegration of orthodontic implants by investigating the healing process of
      the implant-bone interface through histopathological studies and quantitative
      determination. METHODS: Twelve male beagles were selected and randomly divided
      into four groups. An orthodontic microscrew was implanted beside the tooth
      extraction area. Animals were killed in 1, 3, 8, and, 12 weeks to investigate
      tissue response. Histomorphological observation and bone implant contact ratio
      (BIC) tests were performed at different healing time after implantation. RESULTS:
      A new bone was formed on the implant-bone interface of the control group. Bone
      resorptions were also detected in the experimental group 3 weeks after
      implantation. The BIC level of the control groups increased during the first 8
      weeks; no change was observed anymore after the 8th week. On the other hand, the
      BIC value in the experimental group decreased in the first 3 weeks. It then
      increased rapidly and reached its peak of 80.08% in the 8th week. No significant
      difference wa s found between the experimental and control groups in the first 3
      weeks. After the 3rd week, the BIC value of the experimental group (44.35%) was
      lower than that of the control group (55.46%) (P < 0.01). CONCLUSION: The healing
      process after implantation was influenced by tooth extraction. Bone resorption
      was detected at an early stage. However, vigorous bone remodeling was observed
      subsequently.

PMID- 24298806
TI  - [Expression and significance profile of human beta-defensin-2 in salivary gland
      tumors and inflammation].
AB  - OBJECTIVE: To investigate the expression characteristics of human beta-defensin-2
      (HBD-2) mRNA and protein in salivary gland benign and malignant tumor tissues, as
      well as in salivary gland inflammation. METHODS: The expression of HBD-2 in
      salivary gland benign tumor, salivary gland cancer, inflammation tissues and
      normal salivary gland tissues were detected by polymerase chain reaction (PCR),
      real-time polymerase chain reaction (Real-Time PCR) and immunohistochemical. The
      differences expression of HBD-2 mRNA and protein were analyzed. RESULTS: RT-PCR
      results showed that HBD-2 mRNA expression in salivary gland benign tumors,
      salivary gland cancer, and inflammation tissues was 6.468-, 0.334-, and 10.563
      fold higher than that in normal tissues, respectively (P < 0.05). HBD-2 was
      expressed in the nuclei of these organs and malignant tissues. CONCLUSION: HBD-2
      mRNA and protein expressions are significantly increased in salivary gland benign
      tumor tissues and inflammation tissues compared with those in normal salivary
      gland tissues, but are significantly decreased in salivary gland cancer. The
      protein nuclear transfer in salivary gland cancer tissues is also significantly
      increased.

PMID- 24298807
TI  - [Relationships of five periodontal pathogens causing subgingival plaque in
      patients with chronic periodontitis under different periodontal conditions].
AB  - OBJECTIVE: This study aimed to assess the relationship between the distributions
      of Haemophilus aggregatibacter (H. aggregatibacter ), Porphyromonas gingivalis
      (P. gingivalis ), Prevotella intermedia (P. intermedia), Tannerella forsythensis
      (T. forsythensis), and Treponema denticola (T. denticola) in subgingival plaque
      and different periodontal conditions of chronic periodontitis. METHODS: Twenty
      patients (80 sites) with chronic periodontitis and ten healthy subjects (20
      sites) were included. The study sites were distributed into different groups
      according to the differences in their pocket probing depths (PD). The groups were
      described as follows: group A, PD< or = 4 mm; group B, 4 mm < PD < or = 6 mm;
      group C, PD>6 mm. Semi-quantification of the subgingival microorganism samples
      was analyzed by polymerase chain reaction (PCR) and reverse hybridization assay.
      RESULTS: The prevalence rates and quantities of P. gingivalis, P. intermedia, T.
      forsythensis, and T. denticola were significantly higher in groups B and C than
      in the healthy group. Higher prevalence rates and quantities of P. gingivalis
      were detected in group A than in the healthy group. The quantities of T.
      forsythensis and T. denticola were also significantly higher in group C than in
      group B. However, the prevalence rates and quantities ofH. aggregatibacter showed
      no significant difference among the groups. CONCLUSION: The prevalence rates and
      levels ofP. gingivalis, P. intermedia, T. forsythensis, and T. denticola possibly
      increased as the depths of the periodontal pockets increased. The quantity ofP.
      gingivalis was correlated with the early stage of chronic periodontitis. The
      quantities of T. forsythensis and T. denticola were associated with local
      development of moderate or severe chronic periodontitis.

PMID- 24298808
TI  - [Mutation analysis of the RUNX2 gene in a family with cleidocranial dysplasia].
AB  - OBJECTIVE: To analyze the mutations of the RUNX2 gene in a family with
      cleidocranial dysplasia (CCD). METHODS: The general health status of family
      members with CCD was investigated through propositus verification method. Oral
      specialized examination and radiological examination were performed. The
      peripheral venous blood of the proband and her parents and sisters was collected.
      Genomic DNA was extracted, and the RUNX2 gene from this DNA was amplified by
      polymerase chain reaction (PCR). DNA sequences were analyzed with the Blastn
      program. RESULTS: After Blastn analysis, heterozygous C to T transition mutation
      at nucleotide 568 occurred in exon 2, which converted arginine to tryptophane at
      codon 190 (c.568C>T, CGG-->TGG). CONCLUSION: RUNX2 gene is responsible for the
      CCD in the Chinese family under study. The c.568C>T mutation is the molecular
      basis of the CCD in the family.

PMID- 24298809
TI  - [Expression of the estrogen receptor and type II collagen in the mandibular
      condylar cartilage of the human embryo].
AB  - OBJECTIVE: To study the expression of the estrogen receptor (ER) and type II
      collagen in the mandibular condylar cartilage of the human embryo. METHODS: The
      expression and localization of ERalpha, ERbeta, and type II collagen in the
      mandibular condylar cartilage of the human embryo were examined through
      hematoxylin-eosin (HE) and immunohistochemistry staining. RESULTS: Type II
      collagen was primarily localized in the transitional and hypertrophic layers of
      the condylar cartilage. ERa was mostly expressed in the transitional and
      hypertrophic cartilaginous layers of the condylar cartilage. ERa was evenly
      distributed in the cell, whereas ERbeta was localized in the nuclei. No
      expression of type II collagen and ER was found in the fibrage and the
      proliferative layer although minimal expression was found in the calcified
      cartilage. CONCLUSION: The distribution of ER and type II collagen in the
      mandibular condylar cartilage was consistent. Estrogen can selectively combine
      with different subtypes of ER that regulate the ability of the condylar cartilage
      cells to secrete type II collagens.

PMID- 24298810
TI  - [Effects of tooth whitening agents and acidic drinks on the surface properties of
      dental enamel].
AB  - OBJECTIVE: Using tooth whitening agents (bleaching clip) in vitro and acidic
      drinks, we conducted a comparative study of the changes in enamel surface
      morphology, Ca/P content, and hardness. METHODS: Tooth whitening glue pieces,
      cola, and orange juice were used to soak teeth in artificial saliva in vitro.
      Physiological saline was used as a control treatment. The morphology of the four
      groups was observed under a scanning electron microscope (SEM) immediately after
      the teeth were soaked for 7 and 14 d. The changes in Ca/P content and
      microhardness were analyzed. RESULTS: The enamel surfaces of the teeth in the
      three test groups were demineralized. The Ca/P ratio and the average
      microhardness were significantly lower than those of the control group
      immediately after the teeth were soaked (P < 0.05). The Ca/P ratio and
      microhardness gradually increased after 7 d. No significant difference was
      observed between the control group and the test groups after 14 d (P > 0.05).
      CONCLUSION: Bleaching agents caused transient demineralization of human enamel,
      but these agents could induce re-mineralization and repair of enamel over time.
      Demineralization caused by bleaching covered a relatively normal range compared
      with acidic drinks and daily drinking.

PMID- 24298811
TI  - [Ectopic recurrence of ameloblastoma in the bucca region of the mandible: a case
      report].
AB  - The postoperative recurrence of ameloblastoma is common. However, ectopic
      recurrence in clinical operations is rare. A case of ectopic recurrence of
      ameloblastoma in the bucca region of the mandible after 15 years is presented in
      this paper. The causes of the ectopic recurrence were analyzed based on relevant
      literature.

PMID- 24298812
TI  - [Bilateral mandibular fourth molars: a case report].
AB  - The occurrence of supernumerary teeth is a relatively rare dental dysplasia.
      Permanent fourth molars are seldom observed in humans. A case of bilateral
      mandibular fourth molar is reported in this paper.

PMID- 24298813
TI  - [Application of EpiData software in the epidemiological survey of oral health].
AB  - EpiData is a free software designed for data inputting and management in
      epidemiological surveys. This software can enhance the accuracy of data input,
      reduce the error in inputting data, increase work efficiency, and optimize data
      management. The methods of establishing, inputting, and exporting data in the
      EpiData database for oral epidemiological investigations are introduced by
      providing examples in the present study.

PMID- 24298814
TI  - [Indexes used to evaluate the disease activity of Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease that mainly affects the
      exocrine glands. A set of indexes have been established to evaluate the disease
      activity in SS, including symptoms, systemic characteristics, and long-term
      disease damage as well as the patients' quality of life. This article briefly
      introduced the background, content, and scoring rules of SS indexes. Current
      clinical applications and prospects were also reviewed.

PMID- 24298815
TI  - [The role and practice of excellent teachers in the process of stomatology
      innovative talent cultivation].
AB  - To discuss the special role of excellent teachers based on the characters of
      stomatology and the special requirements of personal training, and to describe
      the role of excellent teachers in the process of West China Stomatology School's
      innovative talent cultivation from discussing major teaching problems, building
      excellent teaching team and tutorial system, etc.

PMID- 24298816
TI  - [New anticoagulants: the controversy].

PMID- 24298817
TI  - [Therapeutics. New anticoagulants: stop the controversy!].

PMID- 24298818
TI  - [Your images. Ehlers-Danlos hyperlax].

PMID- 24298819
TI  - [Neuro-ophthalmological complications of sinusitis].
AB  - Sinusitis is a frequent and very often under-diagnosed condition. Despite the
      constantly increasing number of antibiotics with improved efficacy, prevention of
      its complications remains difficult. The prevalence of these complications is
      estimated at 3.7%. Their clinical presentation is highly variable making the
      diagnosis difficult and thereby increasing mortality. In this article,
      historical, epidemiological, pathophysiological, clinical and therapeutic aspects
      of neuro-ophthalmological complications of sinusitis are reviewed. For didactic
      reasons, the various complications have been divided into extra-axial, intra
      axial, vascular, and orbital. Specific paragraph have been devoted to sinusitis
      related bone complications and pain syndromes. It's however obvious that various
      more or less complex associations of these complications can be seen in daily
      practice.

PMID- 24298820
TI  - [Social networks in 10 lessons: # 8 Linkedln: social network for professionals].

PMID- 24298822
TI  - [What is a vitamin?].
AB  - In industrialized countries, the major vitamin deficiency syndromes have
      virtually disappeared. Today they are superseded by marginal deficits,
      characterized by insufficient vitamins reserves to maintain normal physiologic
      state. These states strike populations such as infants, pregnant women,
      alcoholics and the elderly, and may have long-term adverse effects on health.
      This assumption stems from the analysis of studies that show an increase in the
      incidence of various diseases such as cancers and cardiovascular, ocular and
      osteoarticular pathologies in subjects with low vitamin status. Although causal
      relationships are difficult to establish, a huge scope for public health appears
      to be open for vitamins, substituting the notion of minimal intake, indispensable
      to prevent signs of deficiency, to that ensuring optimal health in the medium and
      long-terms. However, the paradoxical character of the results obtained in several
      randomized trials should prompt caution in the use of vitamin supplements to
      prevent chronic diseases.

PMID- 24298821
TI  - [When should we prescribe a vitamin?].

PMID- 24298823
TI  - [Are dosages of vitamins reliable?].

PMID- 24298824
TI  - [Vitamin B1 (thiamine)].
AB  - Vitamin B1 (or thiamine) plays a key role in energy production from glucose.
      Since the main fuel of the nervous system is glucose, thiamine deficiency causes
      severe neurological symptoms. The biological exploration of vitamin B1 status is
      based on the measurement of thiamine pyrophosphate concentration or of the
      activity of a thiamine-dependent enzyme, transketolase, in erythrocytes. Severe
      deficiency states can be observed in chronic alcoholics, after protracted
      vomiting during pregnancy and after bariatric surgery. Mild deficiencies are
      common in the general population, but their clinical consequences are still
      unclear.

PMID- 24298825
TI  - [Vitamin B9].
AB  - Vitamin B9 is represented by the group of folate, whose structure is derived from
      folic acid. The biologically active form is reduced tetrahydrofolates, serving as
      an essential cofactor in methylation reactions, including the vitamin B12
      dependent formation of methionine from homocysteine, and as a carrier of one
      carbon units involved in the synthesis of purines and pyrimidines. Folate
      deficiency is associated with hyperhomocysteinemia, megaloblastic anemia, leuco-
      and thrombocytopenia, cardiovascular disease, embryonic defects, in particular
      neural tube defects, and, possibly, malignancies, depression and cognitive
      impairment.

PMID- 24298826
TI  - [Vitamin B12 (cobalamin)].
AB  - The term "vitamin B12" refers to four cobalamins (Cbl), including methyl-Cbl and
      adenosyl-Cbl, the two enzyme co-factors of methionine synthase and methylmalonyl
      CoA mutase, respectively. Vitamin B12 deficiency produces clinical disorders that
      include mainly megaloblastic anaemia, peripheral and central neurological
      manifestations. The clinical significance of low blood B12 concentrations in the
      absence of manifestations of deficiency is a matter of debate. The biochemical
      diagnosis of the subclinical and clinical deficiency of vitamin B12 has been
      enriched by several parameters, including serum methylmalonic acid, homocysteine,
      and holo-transcobalamine, which have been evaluated over the past two decades.

PMID- 24298827
TI  - [Vitamin C].
AB  - Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables
      foodborne. Vitamin C deficiency is most often due to a lack of daily amount.
      Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia,
      purpura, bleeding disorders, and later by dental manifestations. Biological signs
      are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion
      is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be
      interpreted in light of the acute phase reactants. The treatment is the
      administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion
      (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The
      recommended dietary allowance of vitamin C protect from these risks.

PMID- 24298828
TI  - [Vitamin D].
AB  - There is a recent renewed interest in vitamin D, due to its description as a
      hormone with a positive impact on global health. Even though many former
      epidemiological studies have suggested a possible link between a low vitamin D
      status and the risk of developing chronic diseases, recent data have proven to be
      more discordant or modest. Looking forward to clearly needed randomized
      intervention studies, optimal vitamin D status and intakes should be defined on
      the basis of the vitamin D indisputable effects on calcium homeostasis and
      skeletal mineralization.

PMID- 24298829
TI  - [The frequency of cancer in France].
AB  - Several indicators are available to measure the frequency of cancers, the main
      being incidence and mortality indicators. If one controls for the effects of
      population increase and population aging, the incidence of cancer is increasing
      in France; in the male population the increase is entirely explained by an
      increase in prostate cancer incidence due to screening, widely used despite not
      being recommended by the authorities; in the female population most of the
      increase s explained by increase in breast and lung cancer incidence. Overall
      cancer mortality decreases both in the male and the female population. The
      largest variation is a decrease in male mouth, pharynx, larynx and esophageal
      cancer mortality, due to decreases in the consumption of alcohol and tobacco in
      this population. One observes also important reductions in prostate and lung
      cancer mortality, this last reduction being the result of a decrease in tobacco
      consumption In the female population the largest variation is an increase in lung
      cancer mortality which is the consequence of increasing tobacco consumption.
      These results show the importance of individual behavior on the risk of cancer.

PMID- 24298830
TI  - [Risk of cancer associated with nutrition and physical inactivity].
AB  - Due to the individual and socioeconomic burden of cancer, numerous studies have
      been performed to identify evitable causes. Some cancers could be avoided by
      nutritional prevention measures (practicing physical activity, limiting alcohol
      consumption, preventing overweight) in developed countries, including France.

PMID- 24298831
TI  - [Drugs and cancer risk: the example of THM].
AB  - Estrogen-progestagen menopausal hormone therapy (MHT), indicated for the
      treatment of troublesome climacteric symptoms, is recognized as carcinogenic to
      humans. We present the available epidemiologic evidence concerning its link with
      the risks of breast, ovarian, endometrial and colorectal cancers. While results
      on cancers other than breast cancer are still imprecise or even contradictory,
      there is a clear increase in breast cancer risk associated with the use of
      estrogen-progestagen MHT. Attempts to play down in the public opinion the risk of
      breast cancer associated with these treatments evoke a better prognosis of tumors
      induced by MHT, the fact that MHT would only accelerate the presentation of pre
      existing breast tumors that would otherwise have appeared latter, or that MHT
      would be devoid of risks when initiated close to menopause onset. We show that
      these assertions are not supported by the available epidemiological evidence.

PMID- 24298832
TI  - [Environment and cancer risk].
AB  - Several environmental factors, defined as pollutants present in air, water or
      other media, have been shown to be carcinogenic, including residential exposure
      to asbestos and radon, second-hand tobacco smoke, diesel engine emissions, and
      arsenic contamination of drinking water. Other factors, such as outdoor air
      pollution and water chlorination byproducts, are suspected carcinogens. In the
      case of pesticides and electromagnetic fields, including the use of cell phones,
      the available evidence does not suggest an increased risk of cancer. Overall,
      environmental causes of cancer are responsible for a limited proportion of the
      total burden of cancer in France and other high-income countries. Because of the
      involuntary nature of the exposure and the possibility to implement preventive
      measures, research into environmental cancer remains an important priority.

PMID- 24298833
TI  - [Cancer risk associated to ionizing radiation].
AB  - This article presents an update of the available data on the risk of cancer
      associated with exposure to ionizing radiation. The epidemiological studies
      conducted or continued during the last 10 years have led to improved
      quantification of radiation induced risks at low dose levels, notably by
      extension of the follow-up duration. The results comfort the underlying
      hypotheses of the radiation protection system in use. In particular, they show
      the existence of an increased risk for doses below 100 mSv of for exposures
      protracted over time. These results highlight the relevance of measures to reduce
      all exposures: accidental, medical, occupational or natural, and reinforce the
      importance of a prudent use of medical radiation, particularly for children.

PMID- 24298834
TI  - [The National Resident Matching Program].

PMID- 24298835
TI  - [Eruptive diseases of the children].

PMID- 24298836
TI  - [Principles of a program of quality assurance].

PMID- 24298837
TI  - [Interpretation of epidemiologic studies].

PMID- 24298838
TI  - [Pain in mental disease. Part 1. Physiological basis of pain].

PMID- 24298839
TI  - [Regulatory framework for prescription and recommendations for proper use].

PMID- 24298840
TI  - [Medical recollections. What philosophy and medicine owe to each other].

PMID- 24298841
TI  - Repair of giant ventral hernias.
AB  - Repair of huge ventral hernias is technically challenging for the surgeon and a
      major operation for the patient and should be performed by experienced surgeons
      in centers that are used to caring for patients who are commonly massively obese
      with significant comorbidities. Preoperative medical optimization of patients is
      an important part in the overall management of these large hernias. Conventional
      component separation with retromuscular mesh repair is the workhorse operation,
      which successfully deals with many giant ventral hernias, but multiple
      alternative strategies must be available to address situations in which
      myofascial elements are completely deficient or there is significant loss of
      domain The complexity of this surgery is reflected by recurrence rates ranging
      from 10% to 30% and wound complication rates as high as 40% to 50% in experienced
      centers.

PMID- 24298842
TI  - Laparoscopic colon resection: is it being utilized?
AB  - Since its inception, the use of laparoscopy for colon surgery has slowly
      increased, albeit at a slower rate than for cholecystectomy. Initial concerns
      about the safety and efficacy of laparoscopy have been addressed, and it is now
      known to have several potential short-term and long-term benefits for the
      patient. Early studies likely underestimated use of laparoscopy because of coding
      error. Currently, 40% to 50% of colectomies in the United States are performed
      laparoscopically, with a 10% to 20% rate of conversion to an open operation. The
      definitions oflaparoscopy and conversion to open remain at the discretion of the
      surgeons and their coders. Disparities still exist among use based on several
      patient, hospital, and surgeon factors. In the future, we will likely see a
      continuing increase in use as the new generation of surgeons enters practice, and
      there will be an increasing role for laparoscopy in rectal surgery. The benefit
      and extent of robotic surgery, natural orifice surgery, and single-incision
      surgery for minimally invasive colectomies are yet to be defined.

PMID- 24298843
TI  - Safety of surgical resident training.
AB  - The current structure of residency training allows for safe participation of
      residents in the care of surgical patients. In part, this is likely due to the
      ability of attending-level surgeons and educators to adequately select and
      provide the supervision needed for different levels of residents. Nonetheless,
      efforts have to be made to ensure the optimal safety of patients in several
      settings of modern health care. For laparoscopic surgery, training and simulation
      are highly advisable in preparing residents to perform well in the early stage of
      their learning curves. Attention has to be given to safe and complete hand-offs,
      especially with the increased focus on restricting work hours and the increased
      number of changing shifts. Measures to ensure optimal preparation of surgical
      residents to perform well in stressful situations should also be taken, because
      such situations are an intrinsic part of this specialty. It is only by focusing
      on all these aspects that we can ensure the safety for our patients and provide
      the best possible training for the next generation of surgeons.

PMID- 24298844
TI  - Current management of the Zollinger-Ellison syndrome.
AB  - In summary, ZES is a syndrome caused by gastrinoma, usually located within the
      gastrinoma triangle and associated with symptoms of peptic ulcer disease, GERD,
      and diarrhea. The diagnosis of ZES is made by measuring fasting levels of serum
      gastrin, BAO, and the secretin stimulation test. Because of the high association
      of ZES and MEN1, HPT must be excluded by obtaining a serum calcium and
      parathyroid hormone level. Treatment of ZES consists of medical control of
      symptoms with PPIs and evaluation for potentially curative surgical intervention.
      Noninvasive imaging studies including SRS, CT, and MRI should be performed
      initially to evaluate for metastases and identify resectable disease. Invasive
      imaging modalities such as EUS may be performed to further evaluate primary
      tumors. IOUS, palpation, and duodenotomy are used for intraoperative localization
      of gastrinomas. In patients with MEN1, surgical resection should be pursued only
      if there is an identifiable tumor larger than 2 cm and after surgery for the
      primary hyperparathyroidism (3 1/2-gland parathyroidectomy). All patients with
      resectable localized sporadic gastrinoma should undergo surgical exploration,
      even those with biochemical evidence but negative imaging studies. Tumor is most
      commonly found in the duodenum, and the cure rate is high. In patients with liver
      metastases, surgery should be considered if all identifiable tumor can be safely
      removed. A multidisciplinary approach including surgical and nonsurgical
      therapies should be taken in patients with advanced disease.

PMID- 24298845
TI  - What laboratory tests are required for ambulatory surgery?
AB  - Current recommendations from the 2002 ASA Task Force on Preanesthesia Evaluation
      are not specific to ambulatory surgery and are not based on strongly designed and
      adequately powered studies. Furthermore, although the ASA does not advocate
      routine testing or testing without indication, the guidelines for "selective" or
      "indicated" testing are unclear. As a result, preoperative testing in the United
      States is overused relative to the current ASA Task Force recommendations.
      Uncertainty regarding indications leads to wide variation in the use of
      preoperative testing across providers. There is evidence to suggest that current
      guidelines may recommend testing more than is necessary. Several studies reviewed
      in this article have shown that the elimination of routine testing and more
      selective use based on patient history and physical examination findings would
      decrease cost and increase patient satisfaction without detriment to patient
      care. Future studies should evaluate the effectiveness of testing in specific
      clinical situations, allowing for identification of clear conditions under which
      preoperative testing should be performed. This approach would allow the
      promulgation of clear guidelines, the development of which should involve
      surgeons (as members of a multidisciplinary team), anesthesiologists, and
      hospital administrators, together with governing bodies such as the ASA and
      American College of Surgeons that offer support for the dissemination and broad
      adoption of guidelines. In the future, studies should focus not only on
      identifying specific clinical situations whereby preoperative testing will be
      beneficial but also on determining current barriers to improving adherence to
      guidelines. Potential barriers include institutional policies for testing,
      physician reluctance to change practice, problems in communication between
      members involved in perioperative care, and legal consequences of not ordering
      preoperative tests. Identification of reasons for overuse of testing is the first
      step toward changing practice. Once clear guidelines are developed, the creation
      of preoperative clinics that centralize preoperative care, or promoting the use
      of clinical pathways and/or checklists for determining appropriate tests, may
      improve the adequate use of preoperative tests. It will be critical for quality
      improvement measures to include surgeons, anesthesiologists, hospital
      administrators, and governing bodies such as the ASA and American College of
      Surgeons to achieve success.

PMID- 24298846
TI  - Factors affecting readmission after pancreaticoduodenectomy.
AB  - PD continues to be associated with a high rate of failed discharges, despite
      significant improvements in techniques and postoperative care at high-volume
      centers. Even in the best hands, 1 in 5 patients undergoing PD can be expected to
      require readmission in the early postoperative period. Efforts to minimize
      readmissions must be aimed at identifying high-risk patients, addressing patient
      expectations, establishing patient care plans, and using outpatient resources to
      address anticipated problems and complications.

PMID- 24298847
TI  - Should peritoneal lavage be used with suction during laparoscopic appendectomy
      for perforated appendicitis?

PMID- 24298848
TI  - Appendicitis: changing perspectives.
AB  - Neoplasms are an uncommon finding after appendectomy, with malignant tumors
      occurring in less than 1% of the surgical specimens, and carcinoid being the most
      frequent malignancy. A negative or inconclusive ultrasound is not adequate to
      rule out appendicitis and should be followed by CT scan. For pregnant patients,
      MRI is a reasonable alternative to CT scan. Nonoperative treatment with
      antibiotics is safe as an initial treatment of uncomplicated appendicitis, with a
      significant decrease in complications but a high failure rate. Open and
      laparoscopic appendectomies for appendicitis provide similar results overall,
      although the laparoscopic technique may be advantageous for obese and elderly
      patients but may be associated with a higher incidence of intraabdominal abscess.
      Preoperative diagnostic accuracy is of utmost importance during pregnancy because
      a negative appendectomy is associated with a significant incidence of fetal loss.
      The increased morbidity associated with appendectomy delay suggests that prompt
      surgical intervention remains the safest approach. Routine incidental
      appendectomy should not be performed except in selected cases. Interval
      appendectomy is not indicated because of considerable risks of complications and
      lack of any clinical benefit. Patients older than 40 years with an appendiceal
      mass or abscess treated nonoperatively should routinely have a colonoscopy as
      part of their follow-up to rule out cancer or alternative diagnosis.

PMID- 24298849
TI  - Readmission after abdominal aortic aneurysm repair: what does it mean?
AB  - Thirty-day readmission is common after AAA repair, an d postoperative events are
      strong predictors of readmission after adjusting for comorbidity. In addition,
      readmission is strongly associated with 1-year mortality. Considering the current
      evidence for readmission after AAA repair, improved coordination of care across
      the inpatient, transitional care, and outpatient settings, with active
      surveillance for procedure-specific (EVAR vs open) postoperative complications,
      may prevent some early readmissions. Given the pending financial implications and
      the striking association with 1-year mortality, developing interventions that
      target readmission after AAA repair is of paramount importance in the landscape
      of vascular surgery practice.

PMID- 24298850
TI  - Duodenal switch for morbid obesity: is it safe?

PMID- 24298851
TI  - Is propranolol of benefit in pediatric burn patients?

PMID- 24298853
TI  - The effect of do-not-resuscitate status on postoperative mortality in the elderly
      following emergency surgery.
AB  - Elderly patients who have preexisting DNR orders experience a high incidence of
      mortality and major morbidity within 30 days after emergency general surgery.
      Although not a risk factor for major morbidity, preoperative DNR status does
      represent an independent risk factor for mortality after emergency general
      surgery. The most plausible reason for the excess mortality in DNR patients is
      their decreased willingness to undergo aggressive treatment of major
      postoperative complications. Whether patient-driven failure-to-pursue-rescue also
      explains to some extent the high mortality of non-DNR elderly emergency general
      surgery patients deserves further investigation.

PMID- 24298852
TI  - What is the optimal means of staging colon cancer?
AB  - Although staging for colon cancer has become more complex over time, it is not
      clear that this complexity has improved prognostic assessment. Even with
      revisions in the 7th edition of the AJCC staging system, a clear rank order of
      prognosis from substage to substage has not been established. Improved staging
      models will need to be developed, and attempts at further identifying those high
      risk patients within each stage may be clinically useful. Through improved
      quality measures with lymph node yield, advances in colon cancer staging accuracy
      have been made over the last decade. Determining how to incorporate ultrastaging
      and molecular techniques will be the challenge for future staging models.

PMID- 24298854
TI  - Incidental gall bladder cancer.

PMID- 24298855
TI  - General surgery residency training issues.
AB  - The practice of general surgery has undergone a marked evolution in the past 20
      years, which has been inadequately recognized and minimally addressed. The
      changes that have occurred have been disruptive to residency training, and to
      date there has been inadequate compensation for these. Evidence is now emerging
      of significant issues in the overall performance of recent graduates from at
      least 3 sources: the evaluation of external agents who incorporate these
      graduates into their practice or group, the opinions of the residents themselves,
      and the performance of graduates on the oral examination of the American Board of
      Surgery during the past 8 years. The environmental and technological causes of
      the present situation represent improvements in care for patients, and are
      clearly irreversible. Hence, solutions to the problems must be sought in other
      areas. To address the issues effectively, greater recognition and engagement are
      needed by the surgical community so that effective solutions can be crafted.
      These will need to include improvements in the efficiency of teaching, with the
      assumption of greater individual resident responsibility for their knowledge, the
      establishment of more defined standards for knowledge and skills acquisition by
      level of residency training, with flexible self-assessment available online,
      greater focus of the curriculum on current rather than historical practice,
      increased use of structured assessments (including those in a simulated
      environment), and modifications to the overall structure of the traditional 5
      year residency.

PMID- 24298856
TI  - Is the abdominal aortic aneurysm rupture rate decreasing?
AB  - Decreased smoking has likely had the most significant impact on reducing the
      prevalence of AAAs. In a review of public data in England and Wales, Anjum and
      colleagues illustrated a reduction of AAA rupture from 1997 to2009 across all
      ages attributed to a concurrent decrease in prevalence of smoking. This trend has
      also been noted in a meta-analysis from Sweeting and colleagues and attributed to
      a reduction in the prevalence of smoking since the mid-1970s along with an
      enhanced awareness of cardiovascular risk factor reduction and selective aneurysm
      screening. Along with an effort to reduce AAA progression and rupture, tools to
      predict patient-specific risk of AAA rupture are evolving with refined models
      that incorporate both aneurysm wall stress and wall strength likely to provide
      the most promising approach. Although the role of statins, ACE inhibitors, beta
      blockers, and aspirin in preventing or slowing aneurysmal rupture remains
      unresolved, their proven benefit in reducing long-term cardiovascular mortality
      suggests that these medications should be considered in any patient with a small
      AAA. Currently, randomized trials do not show any survival benefit for open or
      endovascular repair for small aneurysms in the range of 4.0 to 5.4 cm. AAA
      repair, whether through an endovascular or open approach, is not without
      potential complication. Even at centers of excellence, the 30-day mortality rate
      for conventional AAA surgery is 3% to 5%, with rates of major morbidityranging
      from 15% to 40%. The Society for Vascular Surgery guidelines recommends
      surveillance for patients with a fusiform AAA of 4.0 to 5.4 cm. The risk of AAA
      rupture appears to be decreasing through heightened public awareness, advanced
      technology for AAA detection, screening and surveillance, improved understanding
      of biomechanics and natural progression in AAA rupture, along with the
      availability of a wide range of medical therapies for risk factor reduction and
      minimally invasive options for AAA repair.

PMID- 24298857
TI  - Stress-induced hyperglycemia: is it harmful following trauma?
AB  - There is an established association between the presence of SIH and worse
      morbidity and mortality after trauma. However, given the limitations of existing
      data, no definitive statements can be made as to whether aggressive treatment of
      hyperglycemia actually benefits outcome. Although early studies seemed to show a
      clear benefit in surgical ICU patients, subsequent studies have not duplicated
      these results. In addition, severe hypoglycemic episodes associated with glycemic
      control protocols have provided further concern, because they have been
      associated with higher rates of mortality. These disparate outcomes in
      prospective, randomized trials have not allowed definitive conclusions to be
      drawn regarding the exact glucose levels that should be maintained. Regardless,
      some postinjury control of glucose levels is likely necessary. Without data to
      support the practice, tight glycemic control keeping glucose levels below 110
      mg/dL is likely not necessary and probably detrimental to patient outcome. It
      seems that a more moderate level of glycemic control, aimed at providing
      stabilization of glucose levels while reducing hyperglycemic and hypoglycemic
      events, is being practiced in most institutions. Performance of prospective,
      randomized trials in the trauma population along with further advancement and
      refinement of techniques to more precisely reduce glucose variability will
      further clarify the level of glucose control associated with improved outcomes.

PMID- 24298859
TI  - [Dose fractionation in cancer radiotherapy].
AB  - Radiobiological research have enlarged the field of applications of radiotherapy
      in cancer treatment. The study of the biological effects of radiation on tumours
      (T) and normal tissues (NT) has showed that: 1) damage to NT is related directly
      with dose per fraction and inversely with the alpha/beta ratio; 2) the maximum
      differential effect of irradiation between T and NT is obtained when lower doses
      per fraction and shorter time periods are used. One exception to this rule is
      given by T whose alpha/beta ratio is lesser than that of NT. In these T treatment
      with high doses per fraction does increase tumour control and reduce late
      complications.

PMID- 24298860
TI  - [New surgical intervention for correction of vesico-ureteral reflux. Current
      status].
AB  - Vesicoureteral reflux (VUR) with urinary infection is a major risk factor which
      leads to End-stage renal disease and high blood pressure in between 3 and 25% of
      children and between 10 and 15% of adults. Classical techniques for the
      correction of VUR are very aggressive given the delicate structure of terminal
      ureter and they have the disinsertion of the ureteovesical junction, the
      extensive dissection and mobilization of the ureter, the creation of a new
      hiatus, the formation of a submucosal tunnel and the reimplantation of the ureter
      in common. They are very aggressive techniques and create the risk of
      complications such as obstruction due to ischemia and contralateral reflux. The
      new technique that we described in 1984 is based on preserving the anatomical and
      functional integrity of the terminal ureter. The ureters remain intact; they are
      only slid and moved to the midline of the trigone with a simple maneuver where
      they are fixed with one stitch, bloodlessly recovering a greater submucosal
      trajectory ad good muscular support. More than 25 years of experience worldwide
      have made the appraisal unanimous in considering it as the simplest, fastest,
      most effective and less invasive technique whili highlighting the absence of
      complications. This supports its use as one of the primary options in the
      treatment of VUR, giving rise to new applications of the procedure such as in
      secondary VUR in neurogenic bladders and in reflux in ureteral duplication.

PMID- 24298858
TI  - Improvement in the diagnosis of appendicitis.
AB  - Our attempts to systematically improve accuracy in the evaluation of patients
      with suspected appendicitis are, in some ways, hindered by the fact that the
      condition is so frequently straightforward to diagnose. Careful history-taking
      and physical examination are reliable in most patients. However, establishing the
      diagnosis with these skills alone remains vulnerable to conditions that
      masquerade as acute appendicitis. A substantial body of clinical research over
      the last quarter-century has shown that improved accuracy is possible. Strategies
      for improvement include the use of diagnostic scoring systems, laboratory makers
      such as CRP, diagnostic laparoscopy, and advanced imaging modalities such as CT,
      MRI, and US. How clinicians use these strategies depends on many factors related
      to practice setting, the population served, and clinical goals. In children, for
      instance, the desire to limit exposure to ionizing radiation competes with the
      greater anatomic detail that a CT scan can provide; at the same time, many
      hospitals that treat children do not have the resources to maintain the sort of
      full-time, highly sophisticated abdominal US programs that achieve the highest
      rates of diagnostic accuracy in clinical studies. Trade-offs have to be made, but
      improvement is possible in almost all groups of patients: the clinical community
      should no longer settle for a 15% NA rate when 5% is clearly possible without
      adverse consequences. Many clinicians will be faced with the task of evaluating
      patients suspected of having acute appendicitis. A deliberate, proactive, and,
      ideally, benchmarked strategy for improving diagnosis should be the standard to
      which we hold ourselves and the promise we deliver to our patients.

PMID- 24298861
TI  - [Multidrug-resistant organisms (MDROs) in healthcare associated infections
      (H.A.Is): one threat above].
AB  - The use of antimicrobials has meant for humanity one of the biggest progresses in
      our recent History and has enhanced an improvement in living conditions (with
      different nuances depending on the levels of development). Handling of infectious
      diseases by curing the patient and limiting the transmissions source has been a
      very remarkable achievement from Public Health, since the second half of the 20th
      Century. The antibiotic resistance has been recognized with different levels of
      attention, but it has been acknowledged from the beginning of the Antibiotics
      era, with different levels of attention. In this sense Paul Ehlrich (1908),
      father of modern chemotherapy, observed during the trypanosomiasis treatment that
      the pathogen emerged as a resistant variant after the use of an arsenical
      compound. Neuschlosz S. also describes in 1919 the resistance to quinine. But it
      was in the 20th century, that with the development of the specific
      investigations, the pharmaceutical industry, the great therapeutic antimicrobial
      arsenal, the widespread use of such drugs, and the spectacular progress of
      Medicine, has achieved throughout time (1942-2012) the appearance of the
      selection of pathogenic bacteria resistant to different antibiotics, classes and
      families. And with it, the appearance behind selection, of multiresistant (MR)
      bacterias, and currently as an upward phenomenon, with different geographical
      characteristics in developed countries. There is a worldwide concern with certain
      MDRO's, with high microbiological, clinic and prevention interest. Especially, in
      hospitals, for which Clinical Medicine does not have effective drugs, even of the
      latest generation. We are observing that even those antibiotics, may be
      ineffective, with large conse- quences for clinic and Public Health. Nowadays,
      this fact highly concerns the scientific world and the international
      organizations. In particular Grampositive and Gramnegative bacterias, non
      fermenting BGN's, as the causative agents of hospitals care associated/related
      infection, can present these characteristics described above. Amongst them,
      especially are of special concern, MRSA, VRE, GISA, VISA, VRSA, ESBL+
      Enterobacteriaceae Carbapenem Resistant, and also Ps. aeruginosa, Acinetobacter
      baumannii, and S. maltophilia multiresistant. Its microbiological isolation can
      cause different consequences in morbidity (colonization/infection), lethality,
      and difficulty in applying antibiotic treatment protocols, especially the
      empirical ones, and above all, in serious or vulnerable patients in high-risk
      units. Without forgetting, the possibility of exchange of strains, between areas
      of different care specialties, hospitals, or long-stay Centers in the
      community/area. There is an evident risk of therapeutical failure and of
      transmission and clonal spread, to the extent of producing institutional
      outbreaks, with varied impacts, that are very difficult to control and eliminate.
      Certainly, a threat that requires an energetic and an urgent call to action.

PMID- 24298862
TI  - [Roles and traits of woman today and its relation to depressive disorder].
AB  - The femenine labour and school roles have experienced a deep suitable change
      lengthwise last fifty years thanks to the autocontrol of fertility, although the
      psychological traits remain stable. The feminine corporal autoimage works more
      and more as the psychic variable which represents the individual identity. At the
      same time, the annual prevalence of depressive disorder has doubled, even though
      the depressive gender rate has gone down from 3:1 to 2:1 because of women got
      socio-economical independence. Last but no least, the causal factors of
      depressive over incidence in women are studied distributed in five sectors:
      central nervous system, neuroendocrine system, physical condition, personality
      and social environment.

PMID- 24298863
TI  - [Contribution of metabolic sensors on feeding behaviour and the control of body
      weight].
AB  - Metabolic sensors play an important role in the control of food intake,
      utilization of nutrients and demonstration of feeding behaviour. In this work we
      describe the study done in our laboratory on glucokinase (GK) as brain glucose
      sensor, the AMP kinase (AMPK) as detector of the fall of intracellular energy
      charge and as the S6K in the signaling pathway of mTOR with opposite effects to
      AMPK. Glucose sensors are molecular designs that detect with accuracy glucose
      concentrations, facilitating therefore the homeostasis of this hexose. We
      consider GK as a component of a glucose sensor system that might modulates the
      feeding behaviour and indirectly the control of body weight. Our findings
      indicate that GK and GLUT-2 mRNAs and proteins are coexpressed mainly in areas of
      the hypothalamus implied in the control of food intake. We have also found a high
      glucose phosphorylating activity with kinetic properties similar to that reported
      in the liver, with a high apparent Km for glucose that displays no product
      inhibition by glucose-6-phosphate. GK may be also regulated by the presence of
      glucokinase regulatory protein (GKRP), which has been identified in the same
      brain areas than GK. The coexpression of these molecules might play a role as
      glucose sensors in which GLUT-2 has a permissive role and the interactions of GK
      with GKRP made possible a real sensor activity. Furthermore, the effects of
      anorexigenic peptides in this system should facilitate the transduction of
      signals required to produce a state of satiety. Thus, GLP-1 reduced significantly
      the glucose metabolism in areas of the hypothalamus and brainstem related with
      food intake, which open new ways to the study of pathophysiologicals aspects of
      feeding behaviour. Besides we have studied the functions of AMPK and mTOR pathway
      in the hypothalamic areas ventromedial (VMH) and lateral (LH) under situations
      with alterations of the nutritional status and energy balance. Our results
      revealed that the activation of AMPK and S6K in VMH y LH occur in response to the
      changes of glucose concentrations or in the changes in the nutritional state, as
      well as GLP-1/exendin-4 act by counteracting the activation/inactivation of these
      kinases, which support a modulating role of these peptides on the kinases. On the
      other hand, GLP-1/exendin-4 might contribute to the normalization of the altered
      values of these kinases in pathophysiological states such as obesity.

PMID- 24298864
TI  - [Robotics in neuro-rehabilitation].
AB  - Currently the base of the neuro-rehabilitation is the combination of
      neuroplasticity and functional task-based therapies. The stimulation of the brain
      and changes in the effective application of joint in the therapeutic use of
      robots. These devices are applicable for the purpose of functional replacement
      assistance or treatment. We present a review of the current state of technology
      and clinical evidence, as well as ongoing projects and future research in the
      area.

PMID- 24298865
TI  - [The modern microbiology in the clinical managing].
AB  - The tuberculosis is one of the most important and mortal diseases of the world.
      The microbiological confirmatory diagnosis and the microbiological therapeutic
      orientation are fundamental nowadays in the tuberculosis in AIDS and in the
      Resistant tuberculosis. They are described throughout the time by the classic
      Microbiology: From 1882 to final 20th century (130 years). With the modern
      current Microbiology: In the beginning of the 21st century (20-30 years). And as
      will be done with the future Microbiology: From the years 2020-30. The important
      advances are outlined in the modern and future clinical microbiology, for the
      control of the Tuberculosis.

PMID- 24298866
TI  - [Alternative treatments to heart transplant].
AB  - On the past 40 years it has been a significant advance in the Heart Failure
      treatment, both medical and electrical devices, percutaneous revascularization,
      surgery, and circulatory support. With them heart transplantation is no longer an
      essential treatment. Gradually the other techniques are limiting the role of
      heart transplantation in the final treatment of Heart Failure.

PMID- 24298867
TI  - [Residual effect of antiseptics and application to Zero Surgical Site Infection
      (SSI) protocol].

PMID- 24298868
TI  - [Micronucleus test: cytome assay and health biomarker].
AB  - Micronuclei are structures similar to a nucleus but small size and localized in
      the cytoplasm. A micronucleus contents chromosome fragments or whole chromosomes.
      The micronucleus test is considered a biomarker for early induced genetic damage.
      Micronucleus test with cytochalasin B (CBMN test) is used to evaluate genotoxic
      effects induced by physical and chemical environmental agents, and to estimate
      the genetic damage induced in population groups exposed to such agents. After the
      study of large groups of control population, it is estimated that CBMN test can
      be used as a marker of health status with ability to establish a cancer risk.
      Finally, recent studies about the onset of cancer, based on single catastrophic
      events able to originate a cancer, such as chromothripsis or chromoanagenesis,
      are going to understand through an anomalous replication of DNA within the
      micronucleus.

PMID- 24298869
TI  - [Reflections on current records of elite sport].
AB  - The author presents the evolution of elite sport in its technical ways and
      records after the success of the Olympic Games in London (2012). He reflects on
      the limits of the human body in the records of speed, pole vault and high and
      long jumps. At the same time, he comments the situation of the current Spanish
      sport great success. Likewise, he presents the aftermath in the human body from
      other sports like mountaineering and cycling.

PMID- 24298870
TI  - [Past, present and future of the neurosurgery].
AB  - In this work a both historical and current journey for the main pathologies
      regarding the Neurosurgery is achieved, that is to say, the head injuries, the
      brain tumors, the cerebrovascular diseases, the pathology concerning the
      cerebrospinal fluid and malformations, the functional neurosurgery, the
      degenerative spine disease, the spine injuries, the spine tumors and eventually,
      the pathology of the Peripheral and Autonomic Nervous System. Also, references to
      what can be the Neurosurgery in a not very distant future are taken into account.
      Finally, some notes about investigation in the Neurosurgery field are added.

PMID- 24298872
TI  - [Health system sustainability in the crisis context].

PMID- 24298871
TI  - [Polycystic kidney disease: from genetics to dialysis].
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
      cause of end stage renal disease. In addition, end-stage renal disease is
      complicated by acquired polycystic kidney disease. Recent advances in our
      understanding of the pathogenesis of ADPKD have identified the primary cilium as
      key to cystogenesis, and have defined the molecular, cellular and tissue
      pathogenesis of the disease, leading to the design of clinical trials that may
      ultimately lead to effective therapy of the disease. In 2012 a key trial has
      shown that blockade of vasopressin receptors with tolvaptan slows the rate of
      cyst growth and may slow the loss of renal function.

PMID- 24298873
TI  - Elucidation of gephyronic acid biosynthetic pathway revealed unexpected SAM
      dependent methylations.
AB  - Gephyronic acid, a cytostatic polyketide produced by the myxobacterium
      Cystobacter violaceus Cb vi76, exhibits potent and selective eukaryotic protein
      synthesis inhibition. Next-generation sequencing of the C. violaceus genome
      revealed five type I polyketide synthases and post-PKS tailoring enzymes
      including an O-methyltransferase and a cytochrome P450 monooxygenase. Seven
      methyltransferase (MT) domains embedded within the PKS subunits were found to
      install the methyl branches throughout the gephyronic acid skeleton. A rare
      loading domain from the GNAT superfamily also contains an embedded MT domain that
      catalyzes the in situ production of an isobutyryl starter unit. Phylogenetic
      analysis identified new motifs that distinguish MT domains located in PKS
      pathways with in cis acyltransferase (AT) domains from MT domains located in PKS
      pathways with trans AT enzymes. The identification of the gene cluster sets the
      stage for the generation of a heterologous expression system, which will allow
      further investigation of selective eukaryotic protein synthesis inhibitors
      through the generation of gephyronic acid analogues. 

PMID- 24298874
TI  - Content validation of the operational definitions of the nursing diagnoses of
      activity intolerance, excess fluid volume, and decreased cardiac output in
      patients with heart failure.
AB  - OBJECTIVES: To consensually validate the operational definitions of the nursing
      diagnoses activity intolerance, excessive fluid volume, and decreased cardiac
      output in patients with decompensated heart failure. METHOD: Consensual
      validation was performed in two stages: analogy by similarity of defining
      characteristics, and development of operational definitions and validation with
      experts. RESULTS: A total of 38 defining characteristics were found. Operational
      definitions were developed and content-validated. One hundred percent of
      agreement was achieved among the seven experts after five rounds. "Ascites" was
      added in the nursing diagnosis excessive fluid volume. CONCLUSION: The consensual
      validation improves interpretation of human response, grounding the selection of
      nursing interventions and contributing to improved nursing outcomes. IMPLICATIONS
      FOR PRACTICE: Support the assessment of patients with decompensated heart
      failure.

PMID- 24298875
TI  - Switching biological agents for psoriasis in secondary care: a single-centre,
      retrospective, open-label study.

PMID- 24298876
TI  - Maternal BMI and HDL as predictors of pregnancy outcome in women with type 1
      diabetes.
AB  - OBJECTIVE: Diabetes in pregnancy is associated with increased risks of maternal
      as well as foetal complications. METHODS: Retrospective data on 96 women and
      their 96 newborns were anonymously statistically analysed to assess pregnancies
      of type 1 diabetes (T1D) women managed in our hospital in past nine years. The
      outcomes of the neonates were divided into three categories according to the
      clinical status, presence of congenital abnormalities and infant's treatment.
      RESULTS: We found out that the outcome of newborn infants associated with
      maternal HbA1c before gestation as well as during the whole course of pregnancy
      (p < 0.02 for all). Surprisingly, neonatal outcome was strongly associated with
      the maternal BMI (p < 0.05). In our model, a lowering of BMI by one grade led to
      an 18% increase in the chance that the newborn will have no health problems. We
      did not observe an important worsening of chronic diabetic complications in
      mothers; however, regarding maternal clinical status, we found that preeclampsia
      occurrence was strongly and independently connected to HDL level (p < 0.01).
      CONCLUSION: Our data demonstrate that lower pregestational BMI could
      substantially improve T1D mothers' pregnancy outcome. Lower HDL levels in T1D
      mothers during pregnancy correlate with higher risk of preeclampsia development.

PMID- 24298877
TI  - Mechanism of peripheral substituent effects on adsorption-aggregation behaviors
      of cationic porphyrin dyes on tungsten(VI) oxide nanocolloid particles.
AB  - The adsorption and aggregation behaviors of the cationic porphyrin derivatives
      such as 5,10,15,20-tetrakis(4-pyridyl)porphyrin [TPyP], 5,10,15,20-tetrakis(N
      methyl-4-pyridyl)porphyrin [TMPyP], 5,10,15,20-tetrakis(N-ethyl-4
      pyridyl)porphyrin [TEPyP], and 5,10,15,20-tetrakis(N-n-propyl-4-pyridyl)porphyrin
      [TPPyP] (hereafter called "TPyP derivatives") in the tungsten(VI) oxide (WO3)
      colloid aqueous solution at weak acidic pH were studied by UV-vis spectroscopy.
      The TPyP derivatives were strongly adsorbed as monolayer onto the WO3 surface via
      the electrostatic interaction between their peripheral cationic substituents and
      negatively surface-charged WO3 colloid particles, and most of the ones adsorbed
      eventually formed J-type dimers aligned in the head-to-tail fashion. These
      different dimerization states were effectively analyzed by the change of ratios
      among the intensities of exciton split Soret bands (H- and J-bands). Judging from
      the exciton coupling theory and adsorption measurements, we concluded that the J
      dimer geometry of the TPyP derivatives adsorbed on the WO3 colloid particle
      surface is strongly dependent on the presence and difference of peripheral
      substituents. The results described here indicate a new and promising way of
      designing surface supramolecular structures combination of two principles, the
      self-association of organic dyes, and the steric repulsive interaction between
      the peripheral substituents and the inorganic semiconductor surfaces. 

PMID- 24298878
TI  - Robust affinity standards for Cu(I) biochemistry.
AB  - The measurement of reliable Cu(I) protein binding affinities requires competing
      reference ligands with similar binding strengths; however, the literature on such
      reference ligands is not only sparse but often conflicting. To address this
      deficiency, we have created and characterized a series of water-soluble
      monovalent copper ligands, MCL-1, MCL-2, and MCL-3, that form well-defined, air
      stable, and colorless complexes with Cu(I) in aqueous solution. X-ray structural
      data, electrochemical measurements, and an extensive network of equilibrium
      titrations showed that all three ligands form discrete Cu(I) complexes with 1:1
      stoichiometry and are capable of buffering Cu(I) concentrations between 10(-10)
      and 10(-17) M. As most Cu(I) protein affinities have been obtained from
      competition experiments with bathocuproine disulfonate or 2,2'-bicinchoninic
      acid, we further calibrated their Cu(I) stability constants against the MCL
      series. To demonstrate the application of these reagents, we determined the Cu(I)
      binding affinity of CusF (log K = 14.3 +/- 0.1), a periplasmic metalloprotein
      required for the detoxification of elevated copper levels in Escherichia coli .
      Altogether, this interconnected set of affinity standards establishes a reliable
      foundation that will facilitate the precise determination of Cu(I) binding
      affinities of proteins and small-molecule ligands.

PMID- 24298879
TI  - Estimating screening-level organic chemical half-lives in humans.
AB  - Relatively few measured data are available for the thousands of chemicals
      requiring hazard and risk assessment. The whole body, total elimination half-life
      (HLT) and the whole body, primary biotransformation half-life (HLB) are key
      parameters determining the extent of bioaccumulation, biological concentration,
      and risk from chemical exposure. A one-compartment pharmacokinetic (1-CoPK) mass
      balance model was developed to estimate organic chemical HLB from measured HLT
      data in mammals. Approximately 1900 HLs for human adults were collected and
      reviewed and the 1-CoPK model was parametrized for an adult human to calculate
      HLB from HLT. Measured renal clearance and whole body total clearance data for
      306 chemicals were used to calculate empirical HLB,emp. The HLB,emp values and
      other measured data were used to corroborate the 1-CoPK HLB model calculations.
      HLs span approximately 7.5 orders of magnitude from 0.05 h for nitroglycerin to 2
      * 10(6) h for 2,3,4,5,2',3',5',6'-octachlorobiphenyl with a median of 7.6 h. The
      automated Iterative Fragment Selection (IFS) method was applied to develop and
      evaluate various quantitative structure-activity relationships (QSARs) to predict
      HLT and HLB from chemical structure and two novel QSARs are detailed. The HLT and
      HLB QSARs show similar statistical performance; that is, r(2) = 0.89, r(2-ext) =
      0.72 and 0.73 for training and external validation sets, respectively, and root
      mean-square errors for the validation data sets are 0.70 and 0.75, respectively. 

PMID- 24298880
TI  - Asymmetric wettability of nanostructures directs leidenfrost droplets.
AB  - Leidenfrost phenomena on nano- and microstructured surfaces are of great
      importance for increasing control over heat transfer in high power density
      systems utilizing boiling phenomena. They also provide an elegant means to direct
      droplet motion in a variety of recently emerging fluidic systems. Here, we report
      the fabrication and characterization of tilted nanopillar arrays (TNPAs) that
      exhibit directional Leidenfrost water droplets under dynamic conditions, namely
      on impact with Weber numbers >=40 at T >= 325  degrees C. The directionality for
      these droplets is opposite to the direction previously exhibited by macro- and
      microscale Leidenfrost ratchets where movement against the tilt of the ratchet
      was observed. The batch fabrication of the TNPAs was achieved by glancing-angle
      anisotropic reactive ion etching of a thermally dewet platinum mask, with mean
      pillar diameters of 100 nm and heights of 200-500 nm. In contrast to previously
      implemented macro- and microscopic Leidenfrost ratchets, our TNPAs induce no
      preferential directional movement of Leidenfrost droplets under conditions
      approaching steady-state film boiling, suggesting that the observed droplet
      directionality is not a result of the widely accepted mechanism of asymmetric
      vapor flow. Using high-speed imaging, phase diagrams were constructed for the
      boiling behavior upon impact for droplets falling onto TNPAs, straight nanopillar
      arrays, and smooth silicon surfaces. The asymmetric impact and directional
      trajectory of droplets was exclusive to the TNPAs for impacts corresponding to
      the transition boiling regime, linking asymmetric surface wettability to
      preferential directionality of dynamic Leidenfrost droplets on nanostructured
      surfaces. 

PMID- 24298881
TI  - Toward stronger transcrystalline layers in poly(L-lactic acid)/natural fiber
      biocomposites with the aid of an accelerator of chain mobility.
AB  - Formation of transcrystalline layer probably enhances the interfacial adhesion of
      poly(L-lactic acid) (PLLA)/natural fiber biocomposites as confirmed by this work.
      We found that a crystallization accelerator, poly(ethylene glycol) (PEG),
      improved chain mobility of PLLA and thus enhanced the growth kinetics of ramie
      fiber-induced transcrystallinity (TC). The direct observation of polarized
      optical microscopy during isothermal crystallization revealed that large-sized TC
      with rapid growth was produced after adding PEG. It could be exemplified by the
      case at 125  degrees C that the growth rate of TC developed in PLLA10 (containing
      10 wt % PEG) achieved 6.1 MUm/min, which was nearly triple that of pure PLLA (2.1
      MUm/min). And interestingly enough, spherulitic nucleation proceeding was largely
      restricted because it was difficult to fulfill the critical size for stable
      nuclei due to the increased chain mobility. Meanwhile, combining the effective
      nucleation activity of ramie fibers and acceleration virtue of PEG offered the
      chance to form prevailing TC texture, instead of rich spherulites dominated in
      pure PLLA. The local structure (including lamellar structure and molecular
      orientation) of transcrystalline layers was further determined, which indicated
      that TC presented alpha crystal form and random lamellar packing derived from the
      moderate nucleating ability. To our surprise, the single fiber reinforced
      composite samples containing prevailing TC textures achieved remarkably higher
      strength compared to that of pure PLLA samples with poorly developed
      transcrystalline layers, as demonstrated by the single-fiber pull-out test.

PMID- 24298882
TI  - Leveraging social networks to immunize every last child.

PMID- 24298883
TI  - Foreword: networking and strengthening health communication in the European
      Union.

PMID- 24298884
TI  - Reporting health communication activities for the prevention and control of
      communicable diseases in Europe.
AB  - Health communication is part of the public health response to the significant
      continuing threat of communicable diseases in Europe. However, the nature and
      extent of health communication activities in the context of Europe aimed at the
      prevention and control of communicable diseases is currently unknown. This
      severely restricts capacity development as neither strengths nor gaps in
      knowledge and practice are evident and therefore cannot be addressed. This
      article reports on the initial phase of a research project aimed at supporting
      the optimal use and development of health communication activities in the
      European Union and the European Economic Area. The study used a mixed-methods
      design-an e-survey and telephone interviews-with participants from 30 countries
      to identify activities, followed by an opportunistic group interview with 15 key
      stakeholders to identify perceived needs of public health bodies in relation to
      identified gaps. Results indicate that health communication activities are not
      clearly delineated in national public health structures and policies, there is an
      emphasis on crisis communication, and limited evaluation of activities and
      education and training opportunities for health communication are required. The
      facilitation of partnership working with a forum for knowledge exchange between
      Member States would enhance efficacious health communication. 

PMID- 24298885
TI  - Interventions for improving population health literacy: insights from a rapid
      review of the evidence.
AB  - The promotion of health literacy is critical to active and informed participation
      in health promotion, disease prevention, and health care. This article reports on
      a rapid review of the evidence concerning effective strategies for improving
      health literacy. This review was undertaken as part of a series of evidence
      reviews commissioned by the European Centre for Disease Prevention and Control
      through the Translating Health Communications Project. The authors searched a
      range of electronic databases and identified six evidence reviews published
      between 2000 and 2011. A narrative synthesis of the findings was then conducted.
      The majority of the published research originated in the United States, and the
      studies reviewed mainly focused on functional health literacy interventions that
      occurred in clinical settings. Considerable gaps in the evidence exist regarding
      the most effective population-level health literacy interventions, particularly
      with regard to communicable diseases. There is a paucity of intervention studies
      conducted on this topic in Europe. Implications of the findings for improving
      population health literacy on the prevention and control of communicable diseases
      in Europe are considered. 

PMID- 24298886
TI  - Promotional communications for influenza vaccination: a systematic review.
AB  - The authors conducted a systematic review that aimed to map current practice and
      identify effective practice in promotional communications for seasonal influenza
      vaccination in Europe. They identified 22 studies from 7 European countries.
      Included studies were primarily outcome evaluations of communications promoting
      vaccination to health care workers and elderly adults. Evidence on communications
      to improve public acceptance was sparse. A range of communication approaches,
      methods, materials, and channels were used, frequently in combination. All forms
      of promotional communications have the potential to increase uptake in health
      care workers and can also improve uptake among patients. There was promising
      evidence that mass communication methods, delivered as standalone activities or
      as one component of a communication mix, can improve uptake in target
      populations. Education for health care workers and improved service delivery are
      common adjuncts to promotional communications that were associated with
      effectiveness. The evidence suggests that personalized communications, combined
      with improved service delivery, might boost rates of uptake among elderly adults.
      Future development of good practice could be enhanced by more systematic, theory
      based intervention design and more detailed reporting of process and outcome
      evaluations. Vaccine hesitancy is increasingly prevalent; more policy and
      research to improve public acceptance should therefore be considered. 

PMID- 24298887
TI  - Reputation, relationships, risk communication, and the role of trust in the
      prevention and control of communicable disease: a review.
AB  - Population-level compliance with health protective behavioral advice to prevent
      and control communicable disease is essential to optimal effectiveness. Multiple
      factors affect perceptions of trustworthiness, and trust in advice providers is a
      significant predeterminant of compliance. While competency in assessment and
      management of communicable disease risks is critical, communications competency
      may be equally important. Organizational reputation, quality of stakeholder
      relationships and risk information provision strategies are trust moderating
      factors, whose impact is strongly influenced by the content, timing and
      coordination of communications. This article synthesizes the findings of 2
      literature reviews on trust moderating communications and communicable disease
      prevention and control. We find a substantial evidence base on risk
      communication, but limited research on other trust building communications. We
      note that awareness of good practice historically has been limited although
      interest and the availability of supporting resources is growing. Good practice
      and policy elements are identified: recognition that crisis and risk
      communications require different strategies; preemptive dialogue and planning;
      evidence-based approaches to media relations and messaging; and building
      credibility for information sources. Priority areas for future research include
      process and cost-effectiveness evaluation and the development of frameworks that
      integrate communication and biomedical disease control and prevention functions,
      conceptually and at scale. 

PMID- 24298888
TI  - Enhancing the role of health communication in the prevention of infectious
      diseases.
AB  - Despite the recognized importance of health communication for disease prevention,
      a gap in knowledge was becoming apparent as regards the extent and nature of its
      use at the European level to support prevention and control of infectious
      diseases. To address this gap, the European Centre for Disease Prevention and
      Control (ECDC) commissioned in 2009 a consortium of universities to undertake a 3
      year research project called "Translating Health Communications." The outcomes of
      this project comprise 2 major areas: (a) primary information gathering to provide
      insights into how health communication activities are currently being used for
      communicable disease prevention in the European Union and European Economic Area
      and (b) synthesis of knowledge on the evidence of use and application of health
      communication approaches. The overview of main findings of the project presented
      in this article highlights the many challenges that remain and the various areas
      of opportunity in order to raise the profile of health communication in the
      prevention of infectious diseases in the European context. 

PMID- 24298891
TI  - Cyclodextrin-based nanosponges: a propitious platform for enhancing drug
      delivery.
AB  - INTRODUCTION: Recently, Nanotechnology is receiving considerable acknowledgment
      due to its potential to combine features that are difficult to achieve by making
      use of a drug alone. Cyclodextrin-based nanosponges are yet another contemporary
      approach for highlighting the advancements which could be brought about in a drug
      delivery system. Statistical analyses have shown that around 40% of currently
      marketed drugs and about 90% of drugs in their developmental phase encounter
      solubility-related problems. Cyclodextrin-based nanosponges have the capacity to
      emerge as a productive approach over conventional cyclodextrins by overcoming the
      disadvantages associated with the latter. AREAS COVERED: This review is intended
      to give an insight regarding cyclodextrin-based nanosponges such as their
      physical and chemical properties. In addition, methods of preparation and
      characterization are discussed along with biocompatibility, and how these
      nanomeric elements can be exploited in developing effective drug formulations.
      EXPERT OPINION: This emerging technology of cyclodextrin-based nanosponges is
      expected to provide technical solutions to the formulation arena and to come up
      with some successful products in the pharmaceutical market. It also has an
      exciting future in the field of therapeutics wherein it can cater site-directed
      drug delivery and hence it possesses vibrant opportunities.

PMID- 24298890
TI  - Mechanism of enhanced superoxide production in the cytochrome b(6)f complex of
      oxygenic photosynthesis.
AB  - The specific rate of superoxide (O2(*-)) production in the purified active
      crystallizable cytochrome b6f complex, normalized to the rate of electron
      transport, has been found to be more than an order of magnitude greater than that
      measured in isolated yeast respiratory bc1 complex. The biochemical and
      structural basis for the enhanced production of O2(*-) in the cytochrome b6f
      complex compared to that in the bc1 complex is discussed. The higher rate of
      superoxide production in the b6f complex could be a consequence of an increased
      residence time of plastosemiquinone/plastoquinol in its binding niche near the
      Rieske protein iron-sulfur cluster, resulting from (i) occlusion of the quinone
      portal by the phytyl chain of the unique bound chlorophyll, (ii) an altered
      environment of the proton-accepting glutamate believed to be a proton acceptor
      from semiquinone, or (iii) a more negative redox potential of the heme bp on the
      electrochemically positive side of the complex. The enhanced rate of superoxide
      production in the b6f complex is physiologically significant as the chloroplast
      generated reactive oxygen species (ROS) functions in the regulation of excess
      excitation energy, is a source of oxidative damage inflicted during
      photosynthetic reactions, and is a major source of ROS in plant cells. Altered
      levels of ROS production are believed to convey redox signaling from the
      organelle to the cytosol and nucleus. 

PMID- 24298893
TI  - Chronologic changes of explanted liver volume and the use of ursodeoxycholic acid
      in patients with end-stage primary biliary cirrhosis.
AB  - AIM: The clinical presentation of Primary biliary cirrhosis (PBC) at the time of
      liver transplantation (LT) may have changed, due to the long-term use of
      ursodeoxycholic acid (UDCA). The aim of this retrospective study was to
      investigate whether the clinical characteristics of LT recipients with PBC have
      changed over the years. METHODS: Of all 421 adults undergoing LT from 1997 to
      2012 at our center, we included 85 recipients with PBC into the present study.
      The 85 recipients were divided into three groups according to the year LT was
      performed: group 1 (1997-2001, n = 29), group 2 (2002-2005, n = 29) and group 3
      (2006-2012, n = 27). RESULTS: There were no significant differences in sex,
      recipient age, Model for End-Stage Liver Disease score, updated Mayo risk score
      for PBC, or liver-related complications except for esophageal varices among the
      three groups. Patients in group 1 were complicated with esophageal varices less
      frequently than those in the other two groups. In older cases, the ratio of
      explanted liver volume to standard liver volume (ELV/SLV) was significantly
      higher, and the duration of pre-LT UDCA treatment was significantly shorter. The
      duration of UDCA treatment was significantly correlated with ELV/SLV. CONCLUSION:
      Recent LT patients were characterized by more frequent portal hypertension and
      more severe liver atrophy, with longer UDCA therapy prior to LT, which might have
      prevented the somewhat rapid progression of liver failure characterized by
      hepatomegaly with insignificant fibrosis or portal hypertension.

PMID- 24298892
TI  - DNA methylation is globally disrupted and associated with expression changes in
      chronic obstructive pulmonary disease small airways.
AB  - DNA methylation is an epigenetic modification that is highly disrupted in
      response to cigarette smoke and involved in a wide spectrum of malignant and
      nonmalignant diseases, but surprisingly not previously assessed in small airways
      of patients with chronic obstructive pulmonary disease (COPD). Small airways are
      the primary sites of airflow obstruction in COPD. We sought to determine whether
      DNA methylation patterns are disrupted in small airway epithelia of patients with
      COPD, and evaluate whether changes in gene expression are associated with these
      disruptions. Genome-wide methylation and gene expression analysis were performed
      on small airway epithelial DNA and RNA obtained from the same patient during
      bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene
      1.0 ST arrays. To control for known effects of cigarette smoking on DNA
      methylation, methylation and gene expression profiles were compared between
      former smokers with and without COPD matched for age, pack-years, and years of
      smoking cessation. Our results indicate that aberrant DNA methylation is (1) a
      genome-wide phenomenon in small airways of patients with COPD, and (2) associated
      with altered expression of genes and pathways important to COPD, such as the NF
      E2-related factor 2 oxidative response pathway. DNA methylation is likely an
      important mechanism contributing to modulation of genes important to COPD
      pathology. Because these methylation events may underlie disease-specific gene
      expression changes, their characterization is a critical first step toward the
      development of epigenetic markers and an opportunity for developing novel
      epigenetic therapeutic interventions for COPD.

PMID- 24298894
TI  - "Which box should I check?": examining standard check box approaches to measuring
      race and ethnicity.
AB  - OBJECTIVE: This study examined methodological concerns with standard approaches
      to measuring race and ethnicity using the federally defined race and ethnicity
      categories, as utilized in National Institutes of Health (NIH) funded research.
      DATA SOURCES/STUDY SETTING: Surveys were administered to 219 economically
      disadvantaged, racially and ethnically diverse participants at Boston Women
      Infants and Children (WIC) clinics during 2010. STUDY DESIGN: We examined
      missingness and misclassification in responses to the closed-ended NIH measure of
      race and ethnicity compared with open-ended measures of self-identified race and
      ethnicity. PRINCIPAL FINDINGS: Rates of missingness were 26 and 43 percent for
      NIH race and ethnicity items, respectively, compared with 11 and 18 percent for
      open-ended responses. NIH race responses matched racial self-identification in
      only 44 percent of cases. Missingness and misclassification were
      disproportionately higher for self-identified Latina(o)s, African-Americans, and
      Cape Verdeans. Race, but not ethnicity, was more often missing for immigrant
      versus mainland U.S.-born respondents. Results also indicated that ethnicity for
      Hispanic/Latina(o)s is more complex than captured in this measure. CONCLUSIONS:
      The NIH's current race and ethnicity measure demonstrated poor differentiation of
      race and ethnicity, restricted response options, and lack of an inclusive
      ethnicity question. Separating race and ethnicity and providing respondents with
      adequate flexibility to identify themselves both racially and ethnically may
      improve valid operationalization.

PMID- 24298895
TI  - Preparedness of paediatric international travellers departing from Athens,
      Greece: an 18-month airport-based survey.
AB  - AIM: The number of children who travel to tropical and subtropical areas has
      increased. This study aimed to assess the preparedness of children departing from
      Greece to Africa and Asia, in terms of vaccination and malaria chemoprophylaxis.
      METHODS: An 18-month airport-based study was conducted in Athens between November
      2011 and April 2013. RESULTS: Of the 183 children studied, 122 (66.7%) had a
      foreign nationality. Their main destinations were the Indian subcontinent
      (43.2%), South-East Asia (30.6%) and sub-Saharan Africa (14.2%). Just under three
      quarters (73.2%) of the children were travelling to visit friends and relatives.
      Forty (21.9%) children had received pretravel services. Children visiting friends
      and relatives sought pretravel services less frequently than those who were not
      (17.9% versus 32.7%; p = 0.033). Female children and Greek nationals were
      significantly more likely to seeking pretravel services than males and foreign
      nationals (p = 0.007 and <0.001, respectively). The rabies and the typhoid fever
      vaccines were administered inadequately to children travelling to endemic areas,
      but malaria chemoprophylaxis was generally justified. CONCLUSION: Travel medicine
      services for children in Greece should be improved. There is a particular need to
      communicate with the parents of children visiting friends and relatives.

PMID- 24298896
TI  - Lessons learned during an in-flight medical emergency: case report and
      discussion.
AB  - The following case report details an in-flight medical emergency (IFME) that
      occurred during a trans-continental flight while the authors were en route to a
      medical conference. The report highlights the necessity for an improved approach
      to the prevention and management of IFMEs. 

PMID- 24298897
TI  - Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an
      intermediate endpoint for drug development in metastatic castration-resistant
      prostate cancer.
AB  - OBJECTIVE: To investigate the association of radiographic progression defined by
      Prostate Cancer Working Group (PCWG)-2 guidelines and overall survival (OS) in
      men with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND
      METHODS: Two trials that used PCWG-2 guidelines to define progression were
      analysed: a randomized phase II trial (n = 221) comparing first-line docetaxel
      prednisone plus AT-101 or placebo, and a phase III trial (n = 873) comparing
      prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox
      proportional hazards regression models were used to estimate the association of
      radiographic progression with OS. Landmark analyses compared progressing patients
      with those who had not progressed. Sub-analyses compared patients removed from
      trial for progression vs other reasons. RESULTS: An increased risk of death was
      seen for radiographic progression at landmark times from 6 to 12 months with
      docetaxel-based therapy (hazard ratio [HR] >1.7 at all time-points). An increased
      risk of death was also seen with post-docetaxel prednisone alone or with
      sunitinib for progression at landmark times from 2 to 8 months (HR >2.7 at all
      time-points). Kendall's tau was 0.50 (P < 0.001) in the setting of docetaxel
      based therapy and 0.34 (P < 0.001) in the post-docetaxel setting for association
      between radiographic progression and death amongst patients with both events.
      Removal from study due to radiographic progression was associated with a
      significantly lower OS compared with removal for other reasons in both trials.
      Limitations of a retrospective analysis apply and there was no central radiology
      review. CONCLUSIONS: Radiographic progression by PCWG-2 criteria was
      significantly associated with OS in patients with mCRPC receiving first-line
      docetaxel-based chemotherapy or post-docetaxel therapy. With external validation
      as a surrogate endpoint in trials showing survival benefits, the use of
      radiographic progression-free survival may expedite drug development in mCRPC,
      which has been hampered by the lack of intermediate endpoints.

PMID- 24298898
TI  - Mycoplasma superantigen initiates a TLR4-dependent Th17 cascade that enhances
      arthritis after blocking B7-1 in Mycoplasma arthritidis-infected mice.
AB  - Mycoplasma arthritidis is a natural pathogen of rodents causing arthritis, toxic
      shock and necrotizing fasciitis. It secretes a potent superantigen (SAg), MAM,
      that differentially affects the immune system depending upon presence or absence
      of TLR4, thus potentially influencing disease outcomes. Here, we establish that
      antibody to co-stimulatory molecule B7-1(CD80) enhances arthritis in wild-type
      C3H/HeSnJ (TLR2+4+) mice but suppresses arthritis in TLR4-defect C3H/HeJ (TLR2+4
      ) mice. Also, blockade of the B7-1/CD28 co-stimulatory pathway in C3H/HeSnJ mice
      resulted in a marked increase in an alternative co-stimulatory pathway ICOS/ICOSL
      that was associated with elevation of the IL-17/Th17cascade with enhanced IL-23,
      IL-6, and the RORgammat and STAT3 transcriptional factors on CD4+ T cells. Anti-
      B7-1 also increased inflammatory chemokines and the stress protein HMGB1 that
      promotes cellular infiltration to joints. Using a MAM-deficient strain of M.
      arthritidis, a monoclonal antibody to TLR4 and a TLR4-defective mouse strain, we
      established that both MAM and TLR4 are required for the systemic and local joint
      triggering of the Th17/IL-17 cascade in mice treated with anti-B7-1 antibody.
      Importantly, blocking of IL-17 with anti-IL-17 antibody suppressed the elevated
      arthritis in M. arthritidis-infected mice treated with anti-B7-1 antibody. Thus,
      this unique model of arthritis illustrates how microbial agonists can
      bridgeinnate and adaptive immune responses to redirect signalling pathways, thus
      promoting chronic inflammatory and autoimmune disease. 

PMID- 24298899
TI  - Investigation of CTLA-4 and CD86 gene polymorphisms in Iranian patients with
      brucellosis infection.
AB  - The protective immune response against Brucella involves T-cell-mediated
      immunity. T-lymphocyte receptors, CD28 and cytotoxic T-lymphocyte-associated
      protein-4 (CTLA-4), bind the same ligands, CD80 (B7-1) and CD86 (B7-2) on antigen
      presenting cells and regulate T cell activation. CD28 delivers stimulatory
      signals whereas CTLA-4 provides inhibitory signals for T cell activation. Here,
      we investigated the association of four polymorphisms in CTLA4 (+49A/G [rs231775]
      and -318 C/T [rs5742909]) and its ligand CD86 (+1057 G/A [rs1129055] and +2379G/C
      [rs17281995]) with brucellosis infection. The study included 153 Iranian patients
      with active brucellosis and 128 healthy individuals as the control group.
      Genotyping of the CTLA4 and CD86 variants was performed using tetra amplification
      refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and PCR
      restriction fragment length polymorphism analysis, respectively. It was found
      that the CTLA4 -318 CT genotype and T allele were present more frequently in
      cases than in controls and are therefore associated with an increased risk for
      brucellosis (-318 TT genotype; OR = 2.544, P = 0.002). Likewise, the CD86 +1057
      GA and AA genotypes and A allele were associated with an increased risk of
      brucellosis (+1057 AA genotype; OR = 3.81, P = 0.001). However, no statistically
      significant difference between brucellosis patients and controls in the allele
      and genotype distributions of CTLA4, +49A/G (P = 0.859) and CD86, +2379G/C (P =
      0.476) was found. In conclusion, CTLA4 -318 CT genotype and T allele and the CD86
      +057 GA and AA genotypes and A allele play roles as risk factors for developing
      brucellosis infection in Iran.

PMID- 24298900
TI  - Breastfeeding and wheeze prevalence in pre-schoolers and pre-adolescents: the
      Genesis and Healthy Growth studies.
AB  - BACKGROUND: To date, extensive research has been undertaken on a potential link
      of breastfeeding (BF) to wheezing illnesses. Nevertheless, an association remains
      to be established, partly due to age-dependent discrepancies and different
      definitions of exposures/outcomes across studies. We thus investigated the
      relation of diverse infantile feeding patterns with wheeze/asthma prevalence in
      two cohorts of children of different ages (preschool and preadolescent). METHODS:
      Wheeze ever/in the last 12 months (current) and doctor-diagnosed asthma were
      retrospectively reported by parents of the participants of two cross-sectional
      studies: the Genesis study (1871 children aged 1-5) and the Healthy Growth study
      (1884 children aged 9-13). Information on feeding practices (exclusive
      breastfeeding vs. mixed vs. formula feeding) and their duration (2 vs. 4 vs. 6
      months) was recorded. Perinatal and anthorpometric data were also collected.
      RESULTS: In pre-schoolers, regimes that did not entail exclusive BF were
      positively correlated to current/ever wheeze, both before and after adjustment
      for confounders. No differences between the associations of regimes with 2, 4 or
      6 months of exclusive BF with current/ever wheeze were shown. Furthermore, there
      was no consistent correlation of feeding practices with physician-diagnosed
      asthma. In pre-adolescents, no association of infantile feeding patterns with the
      wheeze/asthma outcomes was observed. CONCLUSIONS: Exclusive BF is associated with
      reduced prevalence of current/ever wheeze in pre-schoolers; however, this appears
      to wane in older children. The association of a period of exclusive BF as low as
      2 months with pre-school wheeze prevalence, appeared to be comparable with that
      of 6 months of exclusivity.

PMID- 24298901
TI  - Reduced gray matter volume and increased white matter fractional anisotropy in
      women with hypoactive sexual desire disorder.
AB  - INTRODUCTION: Models of hypoactive sexual desire disorder (HSDD) imply altered
      central processing of sexual stimuli. Imaging studies have identified areas which
      show altered processing as compared with controls, but to date, structural
      neuroanatomical differences have not been described. AIM: The aim of this study
      is to investigate differences in brain structure between women with HSDD and
      women with no history of sexual dysfunction, and to determine sexual behavioral
      correlates of identified structural deviations. METHODS: Sexual functioning and
      gray matter (GM) and white matter (WM) were assessed in 29 women with HSDD and 16
      healthy control subjects of comparable age and socioeconomic status with no
      history of sexual dysfunction. MAIN OUTCOME MEASURES: WM properties were measured
      using diffusion-weighted imaging and analyzed using fractional anisotropy (FA).
      GM volume was measured using three-dimensional T1-weighted recordings and
      analyzed using voxel-based morphometry. Sexual functioning was measured using the
      Sexual Function Questionnaire. RESULTS: Women with HSDD, as compared with
      controls, had reduced GM volume in the right insula, bilateral anterior temporal
      cortices, left occipitotemporal cortex, anterior cingulate gyrus, and right
      dorsolateral prefrontal cortex. Also, increased WM FA was observed within,
      amongst others, the bilateral amygdalae. Sexual interest and arousal correlated
      mostly with GM volume in these regions, whereas orgasm function correlated mostly
      with WM FA. CONCLUSION: HSDD coincides with anatomical differences in the central
      nervous system, in both GM and WM. The findings suggest that decreased salience
      attribution to sexual stimuli, decreased perception of bodily responses and
      sexual emotional stimulus perception, and concomitant altered attentional
      mechanisms associated with sexual response induction.

PMID- 24298903
TI  - Using Google Street View for systematic observation of the built environment:
      analysis of spatio-temporal instability of imagery dates.
AB  - BACKGROUND: Recently, Google Street View (GSV) has been examined as a tool for
      remotely conducting systematic observation of the built environment. Studies have
      found it offers benefits over in-person audits, including efficiency, safety,
      cost, and the potential to expand built environment research to larger areas and
      more places globally. However, one limitation has been the lack of documentation
      on the date of imagery collection. In 2011, Google began placing a date stamp on
      images which now enables investigation of this concern. This study questions the
      spatio-temporal stability in the GSV date stamp. Specifically, is the imagery
      collected contemporaneously? If not, how frequently and where is imagery from
      different time periods woven together to represent environmental conditions in a
      particular place. Furthermore, how much continuity exists in imagery for a
      particular time period? Answering these questions will provide guidance on the
      use of GSV as a tool for built environment audits. METHODS: GSV was used to
      virtually "drive" five sites that are a part of the authors' ongoing studies.
      Each street in the sites was "driven" one mouse-click at a time while observing
      the date stamp on each image. Every time the date stamp changed, this
      "disruption" was marked on the map. Every street segment in the site was coded by
      the date the imagery for that segment was collected. Spatial query and
      descriptive statistics were applied to understand the spatio-temporal patterns of
      imagery dates. RESULTS: Spatio-temporal instability is present in the dates of
      GSV imagery. Of the 353 disruptions, 82.4% occur close to (<25 m) intersections.
      The remainder occurs inconsistently in other locations. The extent of continuity
      for a set of images collected with the same date stamp ranged from 3.13 m to
      3373.06 m, though the majority of continuous segments were less than 400 m.
      CONCLUSION: GSV offers some benefits over traditional built environment audits.
      However, this investigation empirically identifies a previously undocumented
      limitation in its application for research. Imagery dates can change often and
      without warning. Caution should be used at intersections where these disruptions
      are most likely to occur, though caution should be used everywhere when using GSV
      as a data collection tool.

PMID- 24298904
TI  - Two methods to simulate intrapulpal pressure: effects upon bonding performance of
      self-etch adhesives.
AB  - AIM: To evaluate the effects of two methods to simulate physiological pulpal
      pressure on the dentine bonding performance of two all-in-one adhesives and a two
      step self-etch silorane-based adhesive by means of microtensile bond strength
      (MUTBS) and nanoleakage surveys. METHODOLOGY: The self-etch adhesives [G-Bond
      Plus (GB), Adper Easy Bond (EB) and silorane adhesive (SIL)] were applied to flat
      deep dentine surfaces from extracted human molars. The restorations were
      constructed using resin composites Filtek Silorane or Filtek Z350 (3M ESPE).
      After 24 h using the two methods of simulated pulpal pressure or no pulpal
      pressure (control groups), the bonded teeth were cut into specimens and submitted
      to MUTBS and silver uptake examination. Results were analysed with two-way anova
      and Tukey's test (P < 0.05). RESULTS: Both methods of simulated pulpal pressure
      led statistically similar MUTBS for all adhesives. No difference between control
      and pulpal pressure groups was found for SIL and GB. EB led significant drop (P =
      0.002) in bond strength under pulpal pressure. Silver impregnation was increased
      after both methods of simulated pulpal pressure for all adhesives, and it was
      similar between the simulated pulpal pressure methods. CONCLUSIONS: The
      innovative method to simulate pulpal pressure behaved similarly to the classic
      one and could be used as an alternative. The HEMA-free one-step and the two-step
      self-etch adhesives had acceptable resistance against pulpal pressure, unlike the
      HEMA-rich adhesive.

PMID- 24298905
TI  - Impact of vascular thromboxane prostanoid receptor activation on hemostasis,
      thrombosis, oxidative stress, and inflammation.
AB  - The activation of thromboxane prostanoid (TP) receptor on platelets,
      monocytes/macrophages, endothelial cells, and vascular smooth muscle cells (SMC)
      plays important roles in regulating platelet activation and vascular tone and in
      the pathogenesis of thrombosis and vascular inflammation. Oxidative stress and
      vascular inflammation increase the formation of TP receptor agonists, which
      promote initiation and progression of atherogenesis and thrombosis. Furthermore,
      TP receptor activation promotes angiogenesis and vessel wall constriction.
      Besides thromboxane A2 and its endoperoxide precursors, prostaglandin G2 and H2,
      isoprostanes, and 20-hydroxyeicosatetraenoic acid also activate TP receptor as
      autocrine or paracrine ligands. These additional TP activators play a role in
      pathological conditions such as diabetes, obesity, and hypertension, and their
      biosynthesis is not inhibited by aspirin, at variance with that of thromboxane
      A2. The understanding of TP receptor function increased our current knowledge of
      the pathogenesis of atherosclerosis and thrombosis, highlighting the great impact
      that this receptor has in cardiovascular disorders.

PMID- 24298906
TI  - Impact of RNA-seq attributes on false positive rates in differential expression
      analysis of de novo assembled transcriptomes.
AB  - BACKGROUND: High-throughput RNA sequencing studies are becoming increasingly
      popular and differential expression studies represent an important downstream
      analysis that often follow de novo transcriptome assembly. If a lot of attention
      has been given to bioinformatics tools for differential gene expression, little
      has yet been given to the impact of the sequence data itself used in pipelines.
      RESULTS: We tested how using different types of reads from the ones used to
      assemble a de novo transcriptome (both differing in length and pairing
      attributes) could potentially affect differential expression (DE) results. To
      investigate this, we created artificial datasets out of long paired-end RNA-seq
      datasets initially used to build the assembly. All datasets were compared via DE
      analyses and because all samples come from the same sequencing run, DE of genes
      or isoforms can be interpreted as false positives resulting from sequence
      attributes. If the false positive rate for differential gene expression does not
      seem to be strongly affected by sequencing strategy (max. of 3.5%), it could
      reach 12.2% or 28.1% for differential isoform expression depending of the
      pipeline used. The effect of paired-end vs. single-end strategy was found to have
      a much greater impact in terms of false positives than sequence length.
      CONCLUSION: In light of false positive rate results, we recommend using paired
      end over single-end sequences in differential expression studies, even if the
      impact is less serious for differential gene expression.

PMID- 24298907
TI  - Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex
      pulmonary disease. A preliminary study.
AB  - RATIONALE: Patients with Mycobacterium avium complex pulmonary disease are
      frequently administered a combination of clarithromycin, ethambutol, and
      rifampicin. However, rifampicin is known to reduce the serum levels of
      clarithromycin. It remains unclear whether a reduction in clarithromycin serum
      levels influences the clinical outcome of the Mycobacterium avium complex
      pulmonary disease treatment regimen. OBJECTIVES: To compare a three-drug regimen
      (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen
      (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung
      disease. METHODS: In a preliminary open-label study, we randomly assigned newly
      diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium
      avium complex without HIV infection to either the three-drug or the two-drug
      regimen for 12 months. The primary endpoint was the conversion of sputum cultures
      to negative after 12 months of treatment. Patient data were analyzed using the
      intention-to-treat method. MEASUREMENTS AND MAIN RESULTS: Of 119 eligible
      patients, 59 were assigned to the three-drug regimen and 60 to the two-drug
      regimen. The rate of sputum culture conversion was 40.6% with the three-drug
      regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence
      interval, -32.1 to 3.4]). The incidence of adverse events leading to the
      discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two
      drug regimens, respectively. CONCLUSIONS: This preliminary study suggests that
      treatment with clarithromycin and ethambutol is not inferior to treatment with
      clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung
      disease. Our findings justify a larger clinical trial to compare long-term
      clinical outcomes for the two treatment regimens. Clinical trial registered with
      http://www.umin.ac.jp/english/ (UMIN000002819).

PMID- 24298902
TI  - The coding region of the UFGT gene is a source of diagnostic SNP markers that
      allow single-locus DNA genotyping for the assessment of cultivar identity and
      ancestry in grapevine (Vitis vinifera L.).
AB  - BACKGROUND: Vitis vinifera L. is one of society's most important agricultural
      crops with a broad genetic variability. The difficulty in recognizing grapevine
      genotypes based on ampelographic traits and secondary metabolites prompted the
      development of molecular markers suitable for achieving variety genetic
      identification. FINDINGS: Here, we propose a comparison between a multi-locus
      barcoding approach based on six chloroplast markers and a single-copy nuclear
      gene sequencing method using five coding regions combined with a character-based
      system with the aim of reconstructing cultivar-specific haplotypes and genotypes
      to be exploited for the molecular characterization of 157 V. vinifera accessions.
      The analysis of the chloroplast target regions proved the inadequacy of the DNA
      barcoding approach at the subspecies level, and hence further DNA genotyping
      analyses were targeted on the sequences of five nuclear single-copy genes
      amplified across all of the accessions. The sequencing of the coding region of
      the UFGT nuclear gene (UDP-glucose: flavonoid 3-0-glucosyltransferase, the key
      enzyme for the accumulation of anthocyanins in berry skins) enabled the discovery
      of discriminant SNPs (1/34 bp) and the reconstruction of 130 V. vinifera distinct
      genotypes. Most of the genotypes proved to be cultivar-specific, and only few
      genotypes were shared by more, although strictly related, cultivars. CONCLUSION:
      On the whole, this technique was successful for inferring SNP-based genotypes of
      grapevine accessions suitable for assessing the genetic identity and ancestry of
      international cultivars and also useful for corroborating some hypotheses
      regarding the origin of local varieties, suggesting several issues of
      misidentification (synonymy/homonymy).

PMID- 24298909
TI  - Graphene oxide assisted hydrothermal carbonization of carbon hydrates.
AB  - Hydrothermal carbonization (HTC) of biomass such as glucose and cellulose
      typically produces micrometer-sized carbon spheres that are insulating. Adding a
      very small amount of Graphene oxide (GO) to glucose (e.g., 1:800 weight ratio)
      can significantly alter the morphology of its HTC product, resulting in more
      conductive carbon materials with higher degree of carbonization. At low mass
      loading level of GO, HTC treatment results in dispersed carbon platelets of tens
      of nanometers in thickness, while at high mass loading levels, free-standing
      carbon monoliths are obtained. Control experiments with other carbon materials
      such as graphite, carbon nanotubes, carbon black, and reduced GO show that only
      GO has significant effect in promoting HTC conversion, likely due to its good
      water processability, amphiphilicity, and two-dimensional structure that may help
      to template the initially carbonized materials. GO offers an additional advantage
      in that its graphene product can act as an in situ heating element to enable
      further carbonization of the HTC products very rapidly upon microwave
      irradiation. Similar effect of GO is also observed for the HTC treatment of
      cellulose. 

PMID- 24298910
TI  - Hydrogen atom in water from ambient to high temperatures.
AB  - The aqueous hydrogen atom is studied with molecular dynamics simulations from
      ambient temperature to near the critical point. The radial distribution functions
      find a hydrogen atom coordination number of about 13 water molecules at 300 K to
      about 4 water molecules at 646 K. The radial and angular distribution functions
      indicate that first-shell water molecules tend to orient to maximize hydrogen
      bonding interactions with other water molecules. These orientational tendencies
      diminish with temperature. The calculated diffusion coefficient agrees very well
      with experimental results known near ambient temperatures. It fits a simple
      activation model to about 575 K, above which the diffusion becomes much faster
      than predicted by the fit. To temperatures of at least 500 K there is evidence
      for caging on a time scale of about 1 ps, but the evidence disappears at very
      high temperatures. Values of the aqueous hydrogen hyperfine coupling constant are
      obtained by averaging the results of density functional calculations on clusters
      extracted from the simulations. The hyperfine coupling calculations do not agree
      well with experiment for reasons that are not understood now, pointing to the
      need for further research on this problem. 

PMID- 24298908
TI  - Tumor glycolysis as a target for cancer therapy: progress and prospects.
AB  - Altered energy metabolism is a biochemical fingerprint of cancer cells that
      represents one of the "hallmarks of cancer". This metabolic phenotype is
      characterized by preferential dependence on glycolysis (the process of conversion
      of glucose into pyruvate followed by lactate production) for energy production in
      an oxygen-independent manner. Although glycolysis is less efficient than
      oxidative phosphorylation in the net yield of adenosine triphosphate (ATP),
      cancer cells adapt to this mathematical disadvantage by increased glucose up
      take, which in turn facilitates a higher rate of glycolysis. Apart from providing
      cellular energy, the metabolic intermediates of glycolysis also play a pivotal
      role in macromolecular biosynthesis, thus conferring selective advantage to
      cancer cells under diminished nutrient supply. Accumulating data also indicate
      that intracellular ATP is a critical determinant of chemoresistance. Under
      hypoxic conditions where glycolysis remains the predominant energy producing
      pathway sensitizing cancer cells would require intracellular depletion of ATP by
      inhibition of glycolysis. Together, the oncogenic regulation of glycolysis and
      multifaceted roles of glycolytic components underscore the biological
      significance of tumor glycolysis. Thus targeting glycolysis remains attractive
      for therapeutic intervention. Several preclinical investigations have indeed
      demonstrated the effectiveness of this therapeutic approach thereby supporting
      its scientific rationale. Recent reviews have provided a wealth of information on
      the biochemical targets of glycolysis and their inhibitors. The objective of this
      review is to present the most recent research on the cancer-specific role of
      glycolytic enzymes including their non-glycolytic functions in order to explore
      the potential for therapeutic opportunities. Further, we discuss the
      translational potential of emerging drug candidates in light of technical
      advances in treatment modalities such as image-guided targeted delivery of cancer
      therapeutics. 

PMID- 24298911
TI  - Vestibular development in marsupials and monotremes.
AB  - The young of marsupials and monotremes are all born in an immature state,
      followed by prolonged nurturing by maternal lactation in either a pouch or nest.
      Nevertheless, the level of locomotor ability required for newborn marsupials and
      monotremes to reach the safety of the pouch or nest varies considerably: some are
      transferred to the pouch or nest in an egg (monotremes); others are transferred
      passively by gravity (e.g. dasyurid marsupials); some have only a horizontal
      wriggle to make (e.g. peramelid and didelphid marsupials); and others must climb
      vertically for a long distance to reach the maternal pouch (e.g. diprotodontid
      marsupials). In the present study, archived sections of the inner ear and
      hindbrain held in the Bolk, Hill and Hubrecht collections at the Museum fur
      Naturkunde, Berlin, were used to test the relationship between structural
      maturity of the vestibular apparatus and the locomotor challenges that face the
      young of these different mammalian groups. A system for staging different levels
      of structural maturity of the vestibular apparatus was applied to the embryos,
      pouch young and hatchlings, and correlated with somatic size as indicated by
      greatest body length. Dasyurids are born at the most immature state, with the
      vestibular apparatus at little more than the otocyst stage. Peramelids are born
      with the vestibular apparatus at a more mature state (fully developed
      semicircular ducts and a ductus reuniens forming between the cochlear duct and
      saccule, but no semicircular canals). Diprotodontids and monotremes are born with
      the vestibular apparatus at the most mature state for the non-eutherians
      (semicircular canals formed, maculae present, but vestibular nuclei in the
      brainstem not yet differentiated). Monotremes and marsupials reach the later
      stages of vestibular apparatus development at mean body lengths that lie within
      the range of those found for laboratory rodents (mouse and rat) reaching the same
      vestibular stage. 

PMID- 24298912
TI  - Transabdominal coelocentesis as early source of fetal DNA for chromosomal and
      molecular diagnosis.
AB  - This study reports a comparative analysis between results of transabdominal
      coelocentesis and traditional invasive procedure in order to assess the
      usefulness of coelocentesis as a source of fetal DNA for molecular and
      chromosomal analysis. A number of 28 women were included in the study. A
      successful sampling of coelomic fluid was obtained in 25 women by transabdominal
      procedure. A positive amplification of DNA with QF-PCR techniques was obtained in
      90% of cases, while 10% of cases failed to reveal interpretable results. Although
      all samples were cultured, the growth rate was not sufficient to determine
      karyotypes within 2 weeks. Five samples were selected to be analyzed by array
      based comparative genomic hybridization (a-CGH) but the interpretation of these
      results was difficult and ambiguous. Our results suggest that transabdominal
      coelocentesis is suitable for the detection of single DNA variation and for QF
      PCR analysis, while further experiments are needed to develop optimized protocols
      for traditional karyotyping and array-analysis.

PMID- 24298913
TI  - Critical consideration of the multiplicity of experimental and organismic
      determinants of pyrethroid neurotoxicity: a proof of concept.
AB  - Pyrethroids (PYR) are pesticides with high insecticidal activity that may disrupt
      neuronal excitability in target and nontarget species. The accumulated evidence
      consistently showed that this neurophysiologic action is followed by alterations
      in motor, sensorimotor, neuromuscular, and thermoregulatory responses.
      Nevertheless, there are some equivocal results regarding the potency of PYR in
      lab animals. The estimation of potency is an important step in pesticide chemical
      risk assessment. In order to identify the variables influencing neurobehavioral
      findings across PYR studies, evidence on experimental and organismic determinants
      of acute PYR-induced neurotoxicity was reviewed in rodents. A comprehensive
      analysis of these studies was conducted focusing on test material and dosing
      conditions, testing conditions, animal models, and other determinants such as
      testing room temperature. Variations in the severity of the neurotoxicity, under
      lab-controlled conditions, was explained based upon factors including influence
      of animal species and age, test material features such as chemical structure and
      stereochemistry, and dosing conditions such as vehicle, route of exposure, and
      dose volume. If not controlled, the interplay of these factors may lead to large
      variance in potency estimation. This review examined the scope of acute
      toxicological data required to determine the safety of pesticide products, and
      factors and covariates that need to be controlled in order to ensure that
      predictivity and precaution are balanced in a risk assessment process within a
      reasonable time-frame, using acute PYR-induced neurotoxicity in rodents as an
      exemplar. 

PMID- 24298914
TI  - Indoor air quality and sources in schools and related health effects.
AB  - Good indoor air quality in schools is important to provide a safe, healthy,
      productive, and comfortable environment for students, teachers, and other school
      staff. However, existing studies demonstrated that various air pollutants are
      found in classrooms, sometimes at elevated concentrations. Data also indicated
      that poor air quality may impact children's health, in particular respiratory
      health, attendance, and academic performance. Nevertheless, it should be noted
      that there are other adverse health effects that are less documented. Few data
      exist for teachers and other adults that work in schools. Allergic individuals
      seem to be at a higher risk for adverse respiratory health consequences. Air
      quality improvement represents an important measure for prevention of adverse
      health consequences in children and adults in schools. 

PMID- 24298915
TI  - Effectiveness of short prophylactic course of atovaquone-proguanil in travelers
      to sub-saharan Africa.
AB  - BACKGROUND: Current guidelines recommend continuation of atovaquone-proguanil
      (AP) malaria prophylaxis for 7 days after leaving Plasmodium falciparum endemic
      areas. Evidence from clinical studies suggests that discontinuation of AP 1 day
      after exposure ends may be safe and effective. Our objective was to assess the
      effectiveness of short-course AP prophylaxis among travelers to sub-Saharan
      Africa. METHODS: To detect prophylactic failures associated with short-course AP
      prophylaxis discontinued 1 day after return, we conducted active surveillance
      during the years 2010 and 2011, by a retrospective telephone survey 1 to 6 months
      after travelers' return. Passive surveillance data were obtained from the Israel
      Ministry of Health (MOH) malaria registry. RESULTS: Among 485 travelers to sub
      Saharan Africa (cumulative exposure of 4,979 days), 421 (87%) discontinued AP 1
      day after leaving the endemic region (cumulative exposure of 4,337 days). None of
      the 485 travelers reported malaria infection. The MOH malaria registry survey
      included 363 P. falciparum-infected patients during the years 2003 to 2011. The
      majority (n = 305; 84%) did not use any malaria prophylaxis. None of the patients
      had used AP (neither regular nor short course AP) for malaria prophylaxis.
      CONCLUSIONS: We did not detect prophylaxis failures among a group of travelers
      who discontinued AP prophylaxis 1 day after leaving malaria-endemic areas.
      Passive surveillance in Israel did not detect any P. falciparum cases among AP
      users. We recommend further validation of our findings by clinical trials,
      prospective studies, and active surveillance in larger cohorts to assess the
      effectiveness of short-course AP prophylaxis in travelers.

PMID- 24298916
TI  - Role of Thr218 in the light-driven anion pump halorhodopsin from Natronomonas
      pharaonis.
AB  - Halorhodopsin (HR) is an inward-directed light-driven halogen ion pump, and NpHR
      is a HR from Natronomonas pharaonis. Unphotolyzed NpHR binds halogen ion in the
      vicinity of the Schiff base, which links retinal to Lys256. This halogen ion is
      transported during the photocycle. We made various mutants of Thr218, which is
      located one half-turn up from the Schiff base to the cytoplasm (CP) channel, and
      analyzed the photocycle using a sequential irreversible model. Four
      photochemically defined intermediates (P(i), i = 1-4) were adequate to describe
      the photocycle. The third component, P3, was a quasi-equilibrium complex between
      the N and O intermediates, where a N <-> O + Cl- equilibrium was attained. The
      K(d,N<->O) values of this equilibrium for various mutants were determined, and
      the value of Thr (wild type) was the highest. The partial molar volume
      differences between N and O, DeltaV(N->O), were estimated from the pressure
      dependence of K(d,N<->O). A comparison between K(d,N<->O) and DeltaV(N->O) led to
      the conclusion that water entry by the F-helix opening at O may occur, which may
      increase K(d,N<->O). For some mutants, however, large DeltaV(N->O) values were
      found, whereas the K(d,N<->O) values were small. This suggests that the special
      coordination of a water molecule with the OH group of Thr is necessary for the
      increase in K(d,N<->O). Mutants with a small K(d,N<->O) showed low pumping
      activities in the presence of inside negative membrane potential, while the
      mutant activities were not different in the absence of membrane potential. The
      effect of the mutation on the pumping activities is discussed.

PMID- 24298918
TI  - Rapid microarray-based DNA genoserotyping of Escherichia coli.
AB  - In this study, an improvement in the oligonucleotide-based DNA microarray for the
      genoserotyping of Escherichia coli is presented. Primer and probes for additional
      70 O antigen groups were developed. The microarray was transferred to a new
      platform, the ArrayStrip format, which allows high through-put tests in 96-well
      formats and fully automated microarray analysis. Thus, starting from a single
      colony, it is possible to determine within a few hours and a single experiment,
      94 of the over 180 known O antigen groups as well as 47 of the 53 different H
      antigens. The microarray was initially validated with a set of defined reference
      strains that had previously been serotyped by conventional agglutination in
      various reference centers. For further validation of the microarray, 180 clinical
      E. coli isolates of human origin (from urine samples, blood cultures, bronchial
      secretions, and wound swabs) and 53 E. coli isolates from cattle, pigs, and
      poultry were used. A high degree of concordance between the results of classical
      antibody-based serotyping and DNA-based genoserotyping was demonstrated during
      validation of the new 70 O antigen groups as well as for the field strains of
      human and animal origin. Therefore, this oligonucleotide array is a diagnostic
      tool that is user-friendly and more efficient than classical serotyping by
      agglutination. Furthermore, the tests can be performed in almost every routine
      lab and are easily expanded and standardized. 

PMID- 24298917
TI  - Current status of magnetic resonance imaging (MRI) and ultrasonography fusion
      software platforms for guidance of prostate biopsies.
AB  - Prostate MRI is currently the best diagnostic imaging method for detecting PCa.
      Magnetic resonance imaging (MRI)/ultrasonography (US) fusion allows the
      sensitivity and specificity of MRI to be combined with the real-time capabilities
      of transrectal ultrasonography (TRUS). Multiple approaches and techniques exist
      for MRI/US fusion and include direct 'in bore' MRI biopsies, cognitive fusion,
      and MRI/US fusion via software-based image coregistration platforms. 

PMID- 24298920
TI  - Interventions to reduce anxiety, distress and the need for sedation in adult
      patients undergoing magnetic resonance imaging: a systematic review.
AB  - PURPOSE: Adults undergoing MRI scans can experience anxiety, claustrophobia and
      fear during the scanning experience and, in some cases, require sedation. The aim
      of this systematic review was to determine what strategies are effective in
      reducing fear, anxiety and claustrophobia, and the need for sedation in adults
      undergoing MRI. METHODS: A quantitative systematic review, according to the
      methodology of the Joanna Briggs Institute, was carried out. A systematic search
      of a number of databases was performed. Studies were then screened and critically
      appraised by two independent reviewers before being included in the review.
      RESULTS: In total, 21 studies met the inclusion criteria for the review, which
      assessed the following interventions: MRI design features, cognitive-behavioural
      strategies, prone positioning, information, fragrance administration and team
      training. All of these had some positive impact on outcomes. CONCLUSION:
      Healthcare professionals working with adults undergoing MRI may consider some of
      the strategies included in this review to implement in their practice to reduce
      anxiety and increase patient comfort while reducing the need for sedation.

PMID- 24298921
TI  - Post-anaesthetic discharge scoring criteria: key findings from a systematic
      review.
AB  - BACKGROUND: Patient safety depends on nurses' clinical judgment. In post
      anaesthetic care, objective scoring systems are commonly used to help nurses
      assess when a patient is ready to go back to the ward or be discharged home after
      day surgery. Although there are several criteria used to assess patient readiness
      for discharge from the post-anaesthetic care unit, evaluation of the validity and
      reliability of these criteria is scarce. AIMS: This article presents key findings
      from a systematic review conducted to identify the essential components of an
      effective and feasible scoring system to assess patients following surgical
      anaesthesia for discharge from the post-anaesthetic care unit. METHODS: The
      protocol for the systematic review of quantitative studies investigating
      assessment criteria for discharge of adult patients from the post-anaesthetic
      care unit was approved by the Joanna Briggs Institute and conducted consistent
      with the methodology of the Institute. Twelve databases and grey literature, such
      as conference proceedings, were searched for published studies between 1970 and
      2010. Two reviewers independently assessed study eligibility for inclusion.
      Reference lists of included studies were appraised. RESULTS: Eight studies met
      the inclusion criteria; only one was a randomised controlled trial. Variables
      identified as essential when assessing a patient's readiness for discharge from
      the post-anaesthetic care unit were conscious state, blood pressure, nausea and
      vomiting, and pain. Assessment of psychomotor and cognitive recovery and other
      vital signs were also identified as relevant variables to consider. CONCLUSIONS:
      There was limited high-quality research regarding criteria to assess patient
      readiness for discharge from the post-anaesthetic unit. The key recommendations,
      with moderate to high risk of bias, include that assessment of specific variables
      (pain, conscious state, blood pressure, and nausea and vomiting) should be made
      before patient discharge. These key findings have informed a subsequent study to
      reach international consensus on effective assessment criteria and a project to
      test the clinical reliability of a tool for use by nurses in assessing patient
      readiness for discharge from post-anaesthetic care.

PMID- 24298922
TI  - Validity and reliability of the aneroid sphygmomanometer using a paediatric size
      cuff for craniocervical flexion test.
AB  - BACKGROUND: The craniocervical flexion test (CCFT) is generally undertaken using
      a pressure biofeedback unit. However, the high costs of the device limits its
      availability in poorly resourced healthcare settings. The use of alternate
      measures such as the aneroid sphygmomanometer to undertake CCFT need to be
      investigated. OBJECTIVE: The objective of this study was to establish the
      concurrent validity, intra- and inter-rater reliability of the aneroid
      sphygmomanometer using a paediatric size cuff for CCFT in asymptomatic adults.
      METHODS: This cross-sectional observational study involved 300 asymptomatic
      participants randomly allocated to either validity (n = 100), intra-rater (n =
      100) or inter-rater (n = 100) testing. Participants were asked to perform CCFT to
      assess craniocervical flexors performance using the pressure biofeedback unit and
      the aneroid sphygmomanometer with a paediatric cuff. Inter-rater reliability test
      was performed by two different raters on the same day with rest of 30 min between
      tests. An independent observer checked and recorded the pressures noted on the
      pressure dial thus ensuring blinded outcome measurement. Correlation between the
      two instruments was determined by computing the stability coefficient (Pearson
      product moment correlation) and associated P-values for statistical significance.
      Intra-class correlation coefficients and its 95% confidence intervals (CIs) were
      calculated to determine the intra- and inter-rater reliability. RESULTS: The
      concurrent validity of aneroid sphygmomanometer as per Pearson's product moment
      correlation was r = 0.856 for activation score. The intra-class correlation
      coefficients for intra-rater reliability was 0.92 (95% CI 0.89-0.94), and inter
      rater reliability was 0.87 (95% CI 0.80-0.91). CONCLUSION: This study has
      confirmed high concurrent validity, intra- and inter-rater reliability of the
      aneroid sphygmomanometer using a paediatric cuff for CCFT in asymptomatic adults.
      Its use in people with neck pain warrants investigation.

PMID- 24298923
TI  - Content analysis of continuing education for cervical cytology.
AB  - AIM: The purpose of this project was to assess free and low-cost web-based
      continuing education activities to determine if they reflect updated national
      guidelines for cervical cancer screening. METHODS: A qualitative design and
      descriptive statistics were used to conduct a content analysis. An abstraction
      tool was used to evaluate 15 continuing education activities. Data collection was
      conducted between January and February 2013 by two registered nurses. The results
      were recorded independently and compared for agreement between data collectors,
      as well as inter-rater reliability of the data collectors, and the abstraction
      tool was used to collect data for the analysis. RESULTS: The majority of the
      continuing education activities included the updated guidelines for screening
      intervals, the age to begin screening and when to discontinue screening. Most of
      the activities also indicated that human papillomavirus (HPV) DNA testing is not
      recommended for younger women. Very few of the continuing education activities
      included tips for providers to use when counselling patients. CONCLUSIONS: The
      correct information on age-appropriate screening intervals and HPV co-testing was
      included in the continuing education activities reviewed. The areas that were
      largely underrepresented in the continuing education activities were the risk
      factors, prevention measures for transmission of HPV, patient counselling about
      HPV and the appropriate screening practices.

PMID- 24298924
TI  - Informing clinical policy decision-making practices in ambulance services.
AB  - AIM: This study aims to identify the processes and frameworks that support an
      evidence-based approach to clinical policy decision-making practices in ambulance
      services. METHODS: This literature review focused on: (i) the setting (pre
      hospital); and (ii) the process of evidence translation, for studies published
      after the year 2000. Searches of Medline, CINAHL and Google were undertaken.
      Reference lists of eligible publications were searched for relevant articles.
      RESULTS: A total of 954 articles were identified. Of these, 20 full text articles
      were assessed for eligibility and seven full text articles met the inclusion
      criteria. Three provided detailed descriptions of the evidence-based practice
      processes used to inform ambulance service protocol or guideline development or
      review. CONCLUSIONS: There is little published literature that describes the
      processes involved, and frameworks required, to inform clinical policy decision
      making within ambulance services. This review found that processes were iterative
      and involved collaborations across many internal and external stakeholders. In
      several jurisdictions, these were coordinated by a dedicated team. Success
      appears dependent on committed leadership and purposive human and structural
      resources. Although time consuming, structured processes have been developed in
      some jurisdictions to assist decision-making processes. Further insight is likely
      to be obtained from literature published by those from other disciplines.

PMID- 24298925
TI  - Evidence utilisation project: Management of inadvertent perioperative
      hypothermia. The challenges of implementing best practice recommendations in the
      perioperative environment.
AB  - AIMS: The prevention of inadvertent perioperative hypothermia (IPH) remains an
      important issue in perioperative healthcare. The aims of this project were to:
      (i) assess current clinical practice in the management of IPH and (ii) promote
      best practice in the management of IPH in adult operating theatres. METHODS: This
      project from August 2010 to March 2012 utilised a system of audit and feedback to
      implement best practice recommendations. Data were collected via chart audits
      against criteria developed from best practice recommendations for managing IPH.
      Evidence-based best practices, such as consistent temperature monitoring and
      patient warming, were implemented using multifaceted interventions. RESULTS:
      Perioperative records for 73 patients (baseline) and 72 patients (post
      implementation) were audited. Post-implementation audit showed an increase in
      patients with temperatures >36 degrees C admitted to the post-anaesthetic care
      unit (PACU) (8%) and discharged from PACU (28%). The percentage of patients
      receiving preoperative temperature monitoring increased (38%); however, low
      levels of intraoperative monitoring remained (31% of patients with surgery of 30
      min or longer duration). Small increases were found in patient warming of 5%
      intraoperatively and 8% postoperatively. Preoperative warming was not
      successfully implemented during this phase of the project. CONCLUSION:
      Temperature monitoring, warming and rates of normothermia improved; however,
      barriers to best practice of IPH management were experienced, which negatively
      impacted on the project. Further stages of implementation and audit were added to
      further address IPH management in this department.

PMID- 24298926
TI  - High bed occupancy rates: Are they a risk for patients and staff?
AB  - AIM: In order to produce empirical evidence on the relationship between high bed
      occupancy and its potential hazards, this study correlates bed occupancy rates
      with hospital patient safety and staff overload indicators. METHODS: Data from
      nine medium to large scale public hospitals, all pertaining to the Hospital
      Foundation of Minas Gerais, Brazil, were gathered for the period January 2007 to
      June 2011. Indicators were aggregated by month, resulting in 486 observations (54
      months * 9 hospitals). Bivariate linear regressions were performed, aiming to
      estimate the effect of bed occupancy rates on each response variable (hospital
      infection rates, institutional mortality and sick leave incidence). In addition,
      to directly test the hypothesis that bed occupancy rates over 85% are unsafe, it
      was included in the models as a categorical instead of continuous variable, using
      85% as the cut-off value. RESULTS: Bed occupancy rates showed an inverse
      correlation to mortality rates (b = -0.056; P < 0.001) and presented no
      significant correlation to the nosocomial infection rates (P = 0.512). High bed
      occupancy (>85%) was associated with a slight increment of short sick leaves,
      especially short leaves (<7 days) (+0.14%; P = 0.008). CONCLUSIONS: The increase
      in hospital loading was unexpectedly associated with reduced institutional
      mortality and was not related to nosocomial infection incidences. High bed
      occupancy was associated to a slight increment of short sick leaves.

PMID- 24298927
TI  - Periodontitis and type II diabetes: a two-way relationship.
AB  - For many years an association between diabetes and periodontitis has been
      suspected. In more recent times this relationship has been suggested to be
      bidirectional with each condition being able to influence the other. In this
      review the two-way relationship between diabetes and periodontitis is considered.
      For this narrative review a very broad search strategy of the literature was
      developed using both EMBASE and MEDLINE (via PubMed) databases. The reference
      lists from the selected papers were also scanned, and this provided an additional
      source of papers for inclusion and further assessment. The data available suggest
      that diabetes is a risk as well as a modifying factor for periodontitis.
      Individuals with diabetes are more likely to have periodontitis and with
      increased severity when diabetes is uncontrolled/poorly controlled. Possible
      mechanisms of how diabetes affects periodontitis include adipokine-mediated
      inflammation, neutrophil dysfunction, uncoupling of bone and advanced glycation
      end-products-receptor for advanced glycation end-products interaction. Evidence
      is accruing to support how periodontitis can affect diabetes and complications
      associated with diabetes. There is some evidence demonstrating that periodontal
      therapy can result in a moderate improvement in glycaemic control. Available
      evidence indicates that diabetes and peridontitis are intricately interrelated
      and that each condition has the capacity to influence clinical features of each
      other.

PMID- 24298928
TI  - Thought for food: Clinical evidence for the dietary prevention strategy in
      cardiovascular disease.
AB  - A modified diet has been advocated for the past 50 years for prevention of
      cardiovascular disease. The evidence has in the past been largely epidemiological
      and experimental, with relatively limited support from clinical trials. However a
      major element of this strategy, reduction in intake of saturated fats, has
      recently been called into question; the evidence for and against this view is
      critically reviewed. A Cochrane review, and recent trials, have advanced our
      understanding of the role of diet and of optimal dietary recommendation strategy.
      Here we consider these advances in the light of established knowledge.

PMID- 24298933
TI  - Microparticle association and heterogeneity of tumor-derived tissue factor in
      plasma: is it important for coagulation activation?
AB  - BACKGROUND: Tumor-derived tissue factor (TF) activates coagulation in vitro and
      in vivo in an orthotopic model of human pancreatic cancer. Here, we further
      characterized tumor-derived TF in this model. METHODS: Conditioned medium (CM) of
      L3.6pl human pancreatic tumor cells and plasma from nude mice bearing L3.6pl
      tumors were ultracentrifuged, and the pellets were filtered through membranes
      with different pore sizes. The size distribution of particles was analyzed in CM
      or plasma fractions with nanoparticle tracking and dynamic light scattering.
      Human TF antigen and activity were measured in pellets and supernatants with
      ELISA and clotting or thrombin generation assays, respectively. Human
      alternatively spliced TF (asTF) was measured with ELISA. Human TF and thrombin
      antithrombin complex (TAT) concentrations were assessed in plasma of mice
      injected with filtered fractions of CM. RESULTS: Particles in both CM and plasma
      were < 0.4 MUm. TF antigen and activity in the CM were mainly associated with
      microparticles (MP). Approximately 50% of antigen and 20% of activity were
      associated with particles of < 0.1 MUm. Injection of < 0.1 MUm particles into
      mice caused a 30% drop in platelet counts and an increase in TAT levels. In
      contrast, ~ 90% of TF antigen in tumor-bearing mice plasmas was non-sedimentable,
      whereas TF activity was exclusively associated with MP. Particles of < 0.1 MUm
      and the supernatants of both CM and plasma gained TF activity after addition of
      exogenous phospholipids. Although asTF was found in MP-free CM supernatants, it
      was also present in CM and plasma pellets. CONCLUSIONS: Tumor-derived particles
      of < 0.1 MUm and non-sedimentable TF are or can become procoagulant in the
      presence of phospholipids, and may contribute to the procoagulant potential of
      circulating TF.

PMID- 24298934
TI  - Microalgal-biotechnology as a platform for an integral biogas upgrading and
      nutrient removal from anaerobic effluents.
AB  - The potential of a pilot high rate algal pond (HRAP) interconnected via liquid
      recirculation with an external absorption column for the simultaneous removal of
      H2S and CO2 from biogas using an alkaliphilic microalgal-bacterial consortium was
      evaluated. A bubble column was preferred as external absorption unit to a packed
      bed column based on its ease of operation, despite showing a comparable CO2 mass
      transfer capacity. When the combined HRAP-bubble column system was operated under
      continuous mode with mineral salt medium at a biogas residence time of 30 min in
      the absorption column, the system removed 100% of the H2S (up to 5000 ppmv) and
      90% of the CO2 supplied, with O2 concentrations in the upgraded biogas below
      0.2%. The use of diluted centrates as a free nutrient source resulted in a
      gradual decrease in CO2 removal to steady values of 40%, while H2S removal
      remained at 100%. The anaerobic digestion of the algal-bacterial biomass produced
      during biogas upgrading resulted in a CH4 yield of 0.21-0.27 L/gVS, which could
      satisfy up to 60% of the overall energy demand for biogas upgrading. This proof
      of concept study confirmed that algal-bacterial photobioreactors can support an
      integral upgrading without biogas contamination, with a net negative CO2
      footprint, energy production, and a reduction of the eutrophication potential of
      the residual anaerobic effluents. 

PMID- 24298935
TI  - Effect of HLA-DP and IL28B gene polymorphisms on response to interferon treatment
      in hepatitis B e-antigen seropositive chronic hepatitis B patients.
AB  - AIM: The reason why the majority of chronic hepatitis B (CHB) patients do not
      respond to conventional interferon (IFN)-alpha or pegylated interferon (PEG IFN)
      treatment has not been formally demonstrated. The aim of this study was to
      investigate the association between single nucleotide polymorphisms (SNPs) and
      response to IFN-alpha or PEG IFN therapy in Chinese patients with CHB. METHODS:
      Four SNPs among the HLA-DPA1, HLA-DPB1 (rs3077 and rs9277535) and IL28B
      (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP
      genotyping assay in 144 hepatitis B e-antigen (HBeAg) seropositive CHB patients
      who had received 6-12 months IFN-alpha or PEG IFN treatment. Patients were
      classified as responders who achieved any of the four targets: (i) the loss of
      HBeAg; (ii) anti-HBe seroconversion; (iii) suppression of hepatitis B virus (HBV)
      DNA level to below 3 log of baseline; and (iv) alanine aminotransferase
      normalization. RESULTS: By multivariate analysis at 6 months of therapy and 6
      months post-therapy, the results showed that rs3077-GG genotype was independently
      associated with higher HBeAg loss rate and anti-HBe seroconversion rate, and
      rs9277535-GG genotype was independently associated with decline of HBV DNA level.
      However, we did not observe the significant association between SNP near IL28B
      and the response to IFN-alpha or PEG IFN treatment. CONCLUSION: This study
      suggested that HLA-DPA1 and HLA-DPB1 variants were significantly associated with
      HBeAg loss, anti-HBe seroconversion and HBV DNA level suppression in HBeAg
      seropositive CHB patients who received IFN-alpha or PEG IFN treatment.

PMID- 24298936
TI  - Autotransplantation of mesiodens for missing maxillary lateral incisor with cone
      beam CT-fabricated model and orthodontics.
AB  - AIM: Autotransplantation is a viable treatment option for a missing tooth when
      there is a suitable donor, especially in adolescents with remaining facial
      growth. This report presents the aesthetic restoration of a missing maxillary
      lateral incisor through orthodontic treatment and autotransplantation of a
      mesiodens using a CBCT-fabricated rapid-prototyping model. SUMMARY: A 14-year-old
      male patient with a congenitally missing maxillary lateral incisor was referred
      from the Department of Orthodontics. The teeth were moved orthodontically to
      regain space for the missing lateral incisor and to close the space of the
      mesiodens after transplantation. A replica of the donor tooth was fabricated from
      a cone-beam computed tomography scan through a rapid-prototyping machine before
      autotransplantation surgery. The model was used to create a socket for the graft
      tooth, thereby shortening the extra-oral time and minimizing the damage to the
      root surface. After transplantation and orthodontic tooth movement, the mesiodens
      was finally restored with an aesthetic laminate restoration. Over 3 years, the
      aesthetics remained excellent, and the transplant functioned normally without any
      signs or symptoms of root resorption. KEY LEARNING POINT: Missing anterior teeth
      may be replaced through a combination of orthodontics, autotransplantation with a
      rapid-prototyping model and prosthodontic restoration, in growing patients.

PMID- 24298937
TI  - Changes in pulmonary tissue structure and KL-6/MUC1 expression in a newborn rat
      model of hyperoxia-induced bronchopulmonary dysplasia.
AB  - Following preterm birth, levels of Krebs von den Lungen-6/mucin 1 (KL-6/MUC1) in
      serum correlate closely with the development of advanced bronchopulmonary
      dysplasia (BPD), but the role of KL-6/MUC1 in the development of BPD is unclear.
      To explore whether a relationship exists between KL-6/MUC1 and pathological
      changes in BPD and verify such a clinical finding, we established a newborn rat
      model of 95% oxygen-induced BPD. The development of pulmonary alveoli was
      evaluated by determining the radial alveolar count (RAC) and examining the
      location, distribution, and expression of KL-6/MUC1 in pulmonary tissues using a
      fluorescent immunoassay, Western blot, and reverse transcription polymerase chain
      reaction. The synchronic expression levels of KL-6/MUC1 in serum, bronchoalveolar
      lavage fluid (BALF) and pulmonary tissues were examined using an enzyme-linked
      immunosorbent assay. The mean RAC in the hyperoxia group was significantly lower
      than in normoxia controls, whereas the expression levels of KL-6/MUC1 were
      higher. On days 1, 3, 7, and 14, the mean RACs in hyperoxic rats were 15.00,
      12.67, 12.00, and 11.33, respectively. The expression levels of KL-6/MUC1 peaked
      in the experimental group on day 1, and began to decrease slightly after day 3.
      The expression levels of KL-6/MUC1 in serum and BALF were associated with KL
      6/MUC1 expression in pulmonary tissues. We suggest that increased lung KL-6/MUC1
      expression appears to be closely associated with impairment of alveolarization in
      a newborn rat model of hyperoxia-induced BPD. Changes in lung KL-6/MUC1
      expression can be evaluated effectively and less invasively by monitoring KL
      6/MUC1 in serum and BALF.

PMID- 24298938
TI  - Andrographolide antagonizes cigarette smoke extract-induced inflammatory response
      and oxidative stress in human alveolar epithelial A549 cells through induction of
      microRNA-218.
AB  - Andrographolide is a major bioactive labdane diterpenoid isolated from
      Andrographis paniculata and has protective effects against cigarette smoke (CS)
      induced lung injury. This study was done to determine whether such protective
      effects were mediated through modulation of microRNA (miR)-218 expression.
      Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke
      extract (CSE) with or without andrographolide pretreatment and measured the level
      of glutathione, nuclear factor-kappaB (NF-kappaB) activation, proinflammatory
      cytokine production, and miR-218 expression. We found that andrographolide
      pretreatment significantly restored the glutathione level in CSE-exposed A549
      cells, coupled with reduced inhibitor kappaB (IkappaB)-alpha phosphorylation and
      p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218
      expression was significantly upregulated by andrographolide pretreatment. To
      determine the biological role of miR-218, we overexpressed and downregulated its
      expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We
      observed that miR-218 overexpression led to a marked reduction in IkappaB-alpha
      phosphorylation, p65 nuclear accumulation, and NF-kappaB-dependent
      transcriptional activity in CSE-treated A549 cells. In contrast, miR-218
      silencing enhanced IkappaB-alpha phosphorylation and p65 nuclear accumulation in
      cells with andrographolide pretreatment and reversed andrographolide-mediated
      reduction of IL-6 and IL-8 production. In addition, depletion of miR-218
      significantly reversed the upregulation of glutathione levels in A549 cells by
      andrographolide. Taken together, our results demonstrate that andrographolide
      mitigates CSE-induced inflammatory response in A549 cells, largely through
      inhibition of NF-kappaB activation via upregulation of miR-218, and thus has
      preventive benefits in CS-induced inflammatory lung diseases.

PMID- 24298939
TI  - An Evidence-based Guideline for Pediatric Prehospital Seizure Management Using
      GRADE Methodology.
AB  - OBJECTIVE: The objective of this guideline is to recommend evidence-based
      practices for timely prehospital pediatric seizure cessation while avoiding
      respiratory depression and seizure recurrence. METHODS: A multidisciplinary panel
      was chosen based on expertise in pediatric emergency medicine, prehospital
      medicine, and/or evidence-based guideline development. The panel followed the
      National Prehospital EBG Model using the GRADE methodology to formulate
      questions, retrieve evidence, appraise the evidence, and formulate
      recommendations. The panel members initially searched the literature in 2009 and
      updated their searches in 2012. The panel finalized a draft of a patient care
      algorithm in 2012 that was presented to stakeholder organizations to gather
      feedback for necessary revisions. RESULTS: Five strong and ten weak
      recommendations emerged from the process; all but one was supported by low or
      very low quality evidence. The panel sought to ensure that the recommendations
      promoted timely seizure cessation while avoiding respiratory depression and
      seizure recurrence. The panel recommended that all patients in an active seizure
      have capillary blood glucose checked and be treated with intravenous (IV)
      dextrose or intramuscular (IM) glucagon if <60 mg/dL (3 mmol/L). The panel also
      recommended that non-IV routes (buccal, IM, or intranasal) of benzodiazepines
      (0.2 mg/kg) be used as first-line therapy for status epilepticus, rather than the
      rectal route. CONCLUSIONS: Using GRADE methodology, we have developed a pediatric
      seizure guideline that emphasizes the role of capillary blood glucometry and the
      use of buccal, IM, or intranasal benzodiazepines over IV or rectal routes. Future
      research is needed to compare the effectiveness and safety of these medication
      routes.

PMID- 24298940
TI  - The association of preterm birth with severe asthma and atopic dermatitis: a
      national cohort study.
AB  - BACKGROUND: Asthma and atopic dermatitis are both regarded as atopic diseases.
      Being born too early is associated with increased risk of asthma, but some
      studies have indicated that the opposite might be true for atopic dermatitis. We
      explored in more detail the associations between preterm birth, asthma, and
      atopic dermatitis. METHODS: We analyzed data from Norwegian registries with
      prospectively collected data. All live births in Norway from 1967 through 2001
      were followed through 2005 by linking the Medical Birth Registry of Norway to the
      National Insurance Scheme and to Statistics Norway. Only severe asthma and atopic
      dermatitis were registered in the National Insurance Scheme. RESULTS: Of a total
      of 1,760,821 children, we identified 9,349 cases (0.5%) with severe asthma and
      6,930 cases (0.4%) with severe atopic dermatitis. Compared with children born at
      term (37-41 wk gestation), preterm birth was associated with increased odds for
      severe asthma (odds ratio (OR) 1.7 (95% confidence interval (CI): 1.6-1.8) for 32
      36 wk gestation and OR 3.6 (95% CI: 3.1-4.2) for 23-31 wk) and decreased odds for
      severe atopic dermatitis (OR 0.9 (95% CI: 0.8-1.0) for 32-36 wk gestation and OR
      0.7 (95% CI: 0.5-1.0) for 23-31 wk). Adjustment for perinatal and socio
      demographic factors weakened the association between gestational age and severe
      asthma, while slightly strengthening the association between gestational age and
      severe atopic dermatitis. CONCLUSIONS: Preterm birth was associated with
      increased risk of severe asthma and decreased risk of severe atopic dermatitis.

PMID- 24298941
TI  - A population-based study of adults who frequently visit the emergency department
      for acute asthma. California and Florida, 2009-2010.
AB  - RATIONALE: Little is known about adults who frequently visit the emergency
      department (ED) for acute asthma, or the economic impact of this ED use.
      OBJECTIVES: To examine the proportion and patient characteristics of adult
      patients with multiple ED visits for acute asthma and the associated hospital
      charges. METHODS: We analyzed population-based data from the Healthcare Cost and
      Utilization Project state ED and inpatient databases for two large states
      (California and Florida) between 2009 and 2010. We focused on adult asthma
      patients with asthma-related ED visits. Hospital charge data were available only
      for Florida. MEASUREMENTS AND MAIN RESULTS: The final cohort comprised 86,224
      unique patients with 131,907 asthma-related ED visits. Within 1 year of the first
      ED visit, 26% (95% confidence interval, 25-26%) of patients had multiple (two or
      more) ED visits. In a multivariable model adjusting for comorbidities,
      significant predictors of multiple ED visits were black race, Hispanic ethnicity,
      and low socioeconomic status (all P < 0.05). In multivariate modeling in finer
      categories of ED visit number, increasingly stronger associations were found for
      higher numbers of asthma-related ED visits. Total charges were $346 million in
      Florida; patients with multiple ED visits accounted for 57% (95% confidence
      interval, 51-62%) of total charges. CONCLUSIONS: In this population-based cohort,
      26% of patients had multiple asthma-related ED visits within 1 year. These
      patients were more likely to be black, Hispanic, and of lower socioeconomic
      status; they accounted for 57% of asthma-related hospital charges in Florida. To
      improve population health and to control asthma-related health care spending, we
      believe it is imperative to identify and assist adults with frequent asthma
      related ED visits.

PMID- 24298942
TI  - Which factors play a role in Dutch health promotion professionals' decision to
      recruit actively primary schools to use a web-based smoking prevention programme?
AB  - BACKGROUND: Municipal Health Promotion Organisations (MHPOs) play an important
      role in promoting and disseminating prevention programmes, such as smoking
      prevention programmes, in schools. This study identifies factors that may
      facilitate or hinder MHPOs' willingness to recruit actively primary schools to
      use a smoking prevention programme. METHODS: In 2011, 31 Dutch MHPOs were invited
      to recruit schools to use a smoking prevention programme. All MHPO employees
      involved in smoking prevention activities (n = 68) were asked to complete a
      questionnaire assessing psychological factors and characteristics of their
      organisation that might affect their decision to be involved in active
      recruitment of schools. T-tests and multivariate analysis of variance assessed
      potential differences in psychological and organisational factors between active
      and non-active recruiters. RESULTS: A total of 45 professionals returned the
      questionnaire (66.2%). Active recruiters (n = 12) had more positive attitudes (p
      = 0.02), higher self-efficacy expectations (p < 0.01) and formulated more plans
      (p < 0.01) to recruit primary schools, compared with non-active recruiters.
      Organisational factors did not discriminate between active and non-active
      recruiters. CONCLUSIONS: Primarily psychological factors seem to be associated
      with MHPOs' decision to recruit schools actively. This indicates that creating
      more positive attitude, self-efficacy beliefs and formation of plans may help in
      getting more MHPOs involved in active recruitment procedures.

PMID- 24298943
TI  - Construction and validation of an instrument for assessment of the nursing
      diagnosis, risk for infection, in patients following cardiac surgery.
AB  - PURPOSE: To construct and validate a data collection instrument (DCI), and a
      corresponding instructional guide, for assessment of the nursing diagnosis, risk
      for infection, in patients following cardiac surgery. METHODS: Construction of
      conceptual and operational definitions for risk factors based on literature,
      content validation by experts, and clinical validation by clinical nurses.
      FINDINGS: There were significant internal consistency and reproducibility in the
      content validation. In the clinical validation, agreement among nurses was higher
      than 70% for all risk factors. CONCLUSIONS: The DCI was constructed and
      validated. IMPLICATIONS FOR NURSING PRACTICE: This DCI could be used for
      assessment of adult patients after cardiac surgeries worldwide because of its
      detailed cues for risk factors, which facilitate clinical reasoning and
      diagnostic judgment.

PMID- 24298944
TI  - Extracellular synthesis of zinc oxide nanoparticle using seaweeds of gulf of
      Mannar, India.
AB  - BACKGROUND: The biosynthesis of metal nanoparticles by marine resources is
      thought to be clean, nontoxic, and environmentally acceptable "green procedures".
      Marine ecosystems are very important for the overall health of both marine and
      terrestrial environments. The use of natural sources like Marine biological
      resources essential for nanotechnology. Seaweeds constitute one of the
      commercially important marine living renewable resources. Seaweeds such as green
      Caulerpa peltata, red Hypnea Valencia and brown Sargassum myriocystum were used
      for synthesis of Zinc oxide nanoparticles. RESULT: The preliminary screening of
      physico-chemical parameters such as concentration of metals, concentration of
      seaweed extract, temperature, pH and reaction time revealed that one seaweed S.
      myriocystum were able to synthesize zinc oxide nanoparticles. It was confirmed
      through the, initial colour change of the reaction mixture and UV visible
      spectrophotometer. The extracellular biosynthesized clear zinc oxide
      nanoparticles size 36 nm through characterization technique such as DLS, AFM, SEM
      -EDX, TEM, XRD and FTIR. The biosynthesized ZnO nanoparticles are effective
      antibacterial agents against Gram-positive than the Gram-negative bacteria.
      CONCLUSION: Based on the FTIR results, fucoidan water soluble pigments present in
      S. myriocystum leaf extract is responsible for reduction and stabilization of
      zinc oxide nanoparticles. by this approach are quite stable and no visible
      changes were observed even after 6 months. These soluble elements could have
      acted as both reduction and stabilizing agents preventing the aggregation of
      nanoparticles in solution, extracellular biological synthesis of zinc oxide
      nanoparticles of size 36 nm.

PMID- 24298945
TI  - How ions affect the structure of water: a combined Raman spectroscopy and
      multivariate curve resolution study.
AB  - Raman spectroscopy in combination with multivariate curve resolution (Raman-MCR)
      is used to explore the interaction between water and various kosmotropic and
      chaotropic anions. Raman-MCR of aqueous Na-salt (NaI, NaBr, NaNO3, Na2SO4, and
      Na3PO4) solutions provides solute-correlated Raman spectra (SC-spectra) of water.
      The SC-spectra predominantly bear the vibrational characteristics of water in the
      hydration shell of anions, because Na(+)-cation has negligible effect on the OH
      stretch band of water. The SC-spectra for the chaotropic I(-), Br(-), and NO3(-)
      anions and even for the kosmotropic SO4(2-) anion resemble the Raman spectrum of
      isotopically diluted water (H2O/D2O = 1/19; v/v) whose OH stretch band is largely
      comprised by the response of vibrationally decoupled OH oscillators. On the other
      hand, the SC-spectrum for the kosmotropic PO4(3-) anion is quite similar to the
      Raman spectrum of H2O (bulk). Comparison of the peak positions of SC-spectra and
      the Raman spectrum of isotopically diluted water suggests that the hydrogen bond
      strength of water in the hydration shell of SO4(2-) is comparable to that of the
      isotopically diluted water, but that in the hydration shell of I(-), Br(-), and
      NO3(-) anions is weaker than that of the latter. Analysis of integrated area of
      component bands of the SC-spectra reveals ~80% reduction of the delocalization of
      vibrational modes (intermolecular coupling and Fermi resonance) of water in the
      hydration shell of I(-), Br(-), NO3(-), and SO4(2-) anions. In the case of
      trivalent PO4(3-), the vibrational delocalization is presumably reduced and the
      corresponding decrease in spectral response at ~3250 cm(-1) is compensated by the
      increased signal of strongly hydrogen bonded (but decoupled) water species in the
      hydration shell. The peak area-averaged wavenumber of the SC-spectrum increases
      as PO4(3-) < SO4(2-) < NO3(-) < Br(-) < I(-) and indeed suggests strong hydrogen
      bonding of water in the hydration shell of PO4(3-) anion. 

PMID- 24298948
TI  - North Atlantic demersal deep-water fish distribution and biology: present
      knowledge and challenges for the future.
AB  - This paper summarizes knowledge and knowledge gaps on benthic and benthopelagic
      deep-water fishes of the North Atlantic Ocean, i.e. species inhabiting deep
      continental shelf areas, continental and island slopes, seamounts and the Mid
      Atlantic Ridge. While several studies demonstrate that distribution patterns are
      species specific, several also show that assemblages of species can be defined
      and such assemblages are associated with circulatory features and water mass
      distributions. In many subareas, sampling has, however, been scattered,
      restricted to shallow areas or soft substrata, and results from different studies
      tend to be difficult to compare quantitatively because of sampler differences.
      Particularly, few studies have been conducted on isolated deep oceanic seamounts
      and in Arctic deep-water areas. Time series of data are very few and most series
      are short. Recent studies of population structure of widely distributed demersal
      species show less than expected present connectivity and considerable spatial
      genetic heterogeneity and complexity for some species. In other species, genetic
      homogeneity across wide ranges was discovered. Mechanisms underlying the observed
      patterns have been proposed, but to test emerging hypotheses more species should
      be investigated across their entire distribution ranges. Studies of population
      biology reveal greater diversity in life-history strategies than often assumed,
      even between co-occurring species of the same family. Some slope and ridge
      associated species are rather short-lived, others very long-lived, and growth
      patterns also show considerable variation. Recent comparative studies suggest
      variation in life-history strategies along a continuum correlated with depth,
      ranging from shelf waters to the deep sea where comparatively more species have
      extended lifetimes, and slow rates of growth and reproduction. Reproductive
      biology remains too poorly known for most deep-water species, and temporal
      variation in recruitment has only been studied for few deep-water species. A time
      series of roundnose grenadier Coryphaenoides rupestris recruitment spanning three
      decades of fisheries-independent data suggests that abundant year classes occur
      rarely and may influence size structure and abundance even for this long-lived
      species. 

PMID- 24298947
TI  - Natural killer (NK) cell deficit in coronary artery disease: no aberrations in
      phenotype but sustained reduction of NK cells is associated with low-grade
      inflammation.
AB  - Although reduced natural killer (NK) cell levels have been reported consistently
      in patients with coronary artery disease (CAD), the clinical significance and
      persistence of this immune perturbation is not clarified. In this study we
      characterized the NK cell deficit further by determining (i) differentiation
      surface markers and cytokine profile of NK cell subsets and (ii) ability to
      reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell
      subsets and the intracellular cytokine profile in 31 patients with non-ST
      elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA)
      and 37 healthy controls. In blood collected prior to coronary angiography, the
      proportions of NK cells were reduced significantly in non-STEMI and SA patients
      compared with controls, whereas NK cell subset analyses or cytokine profile
      measurements did not reveal any differences across groups. During a 12-month
      follow-up, the proportions of NK cells increased, although not in all patients.
      Failure to reconstitute NK cell levels was associated with several components of
      metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients
      with sustained NK cell deficit, whereas a decline in IL-6 (P < 0.001) was seen in
      patients with a pronounced increase in NK cells. In conclusion, we found no
      evidence that reduction of NK cells in CAD patients was associated with
      aberrations in NK cell phenotype at any clinical stage of the disease.
      Conversely, failure to reconstitute NK cell levels was associated with a
      persistent low-grade inflammation, suggesting a protective role of NK cells in
      CAD.

PMID- 24298949
TI  - Vertical ecology of the pelagic ocean: classical patterns and new perspectives.
AB  - Applications of acoustic and optical sensing and intensive, discrete-depth
      sampling, in concert with collaborative international research programmes, have
      substantially advanced knowledge of pelagic ecosystems in the 17 years since the
      1996 Deepwater Fishes Symposium of the Fisheries Society of the British Isles.
      Although the epipelagic habitat is the best-known, and remote sensing and high
      resolution modelling allow near-synoptic investigation of upper layer biophysical
      dynamics, ecological studies within the mesopelagic and deep-demersal habitats
      have begun to link lower and upper trophic level processes. Bathypelagic
      taxonomic inventories are far from complete, but recent projects (e.g. MAR-ECO
      and CMarZ, supported by the Census of Marine Life programme) have quantitatively
      strengthened distribution patterns previously described for fishes and have
      provided new perspectives. Synthesis of net and acoustic studies suggests that
      the biomass of deep-pelagic fishes may be two to three orders of magnitude
      greater than the total global commercial fisheries landings. Discrete-depth net
      sampling has revealed relatively high pelagic fish biomass below 1000 m in some
      regions, and that gelatinous zooplankton may be key energy vectors for deep
      pelagic fish production. Lastly, perhaps, the most substantive paradigm shift is
      that vertical connectivity among fishes across classical depth zones is prevalent
      suggesting that a whole-water column approach is warranted for deep ocean
      conservation and management. 

PMID- 24298950
TI  - Colonization of the deep sea by fishes.
AB  - Analysis of maximum depth of occurrence of 11 952 marine fish species shows a
      global decrease in species number (N) with depth (x; m): log10 N = -0.000422x +
      3.610000 (r(2)  = 0.948). The rate of decrease is close to global estimates for
      change in pelagic and benthic biomass with depth (-0.000430), indicating that
      species richness of fishes may be limited by food energy availability in the deep
      sea. The slopes for the Classes Myxini (-0.000488) and Actinopterygii (-0.000413)
      follow this trend but Chondrichthyes decrease more rapidly (-0.000731) implying
      deficiency in ability to colonize the deep sea. Maximum depths attained are 2743,
      4156 and 8370 m for Myxini, Chondrichthyes and Actinopterygii, respectively.
      Endemic species occur in abundance at 7-7800 m depth in hadal trenches but appear
      to be absent from the deepest parts of the oceans, >9000 m deep. There have been
      six global oceanic anoxic events (OAE) since the origin of the major fish taxa in
      the Devonian c. 400 million years ago (mya). Colonization of the deep sea has
      taken place largely since the most recent OAE in the Cretaceous 94 mya when the
      Atlantic Ocean opened up. Patterns of global oceanic circulation oxygenating the
      deep ocean basins became established coinciding with a period of teleost
      diversification and appearance of the Acanthopterygii. Within the Actinopterygii,
      there is a trend for greater invasion of the deep sea by the lower taxa in
      accordance with the Andriashev paradigm. Here, 31 deep-sea families of
      Actinopterygii were identified with mean maximum depth >1000 m and with >10
      species. Those with most of their constituent species living shallower than 1000
      m are proposed as invasive, with extinctions in the deep being continuously
      balanced by export of species from shallow seas. Specialized families with most
      species deeper than 1000 m are termed deep-sea endemics in this study; these
      appear to persist in the deep by virtue of global distribution enabling recovery
      from regional extinctions. Deep-sea invasive families such as Ophidiidae and
      Liparidae make the greatest contribution to fish fauna at depths >6000 m. 

PMID- 24298951
TI  - Spatial distribution and life-history aspects of blackspot seabream Pagellus
      bogaraveo (Osteichthyes: Sparidae).
AB  - Spatial distribution and life history aspects of Pagellus bogaraveo in the
      eastern Ionian Sea were investigated using the data from 13 different studies
      carried out in the area from 1983 to 2010. The spatial patterns of the abundance,
      biomass and mean size showed that the species inhabits the shallow waters of the
      shelf (<170 m depth) as juveniles up to a certain size (<180 mm total length, LT
      ), moving to deeper waters of the slope (mainly 400-500 m depth) as adults. The
      spatial pattern of abundance indicated a continuous distribution of the species
      in deep waters, with hot-spot areas of high values, whereas in shallow waters
      distribution was more discontinuous, with higher concentrations of juveniles in
      estuaries and brackish waters. The study of biological aspects of the species
      revealed (1) a difference in the increase in mass between males and females, (2)
      protandrous hermaphroditism, accompanied by the presence of primary females and
      males that do not change sex, (3) a sex ratio in favour of females >250 mm LT ,
      (4) the presence of hermaphrodites between 200 and 370 mm, (5) a long
      reproduction period from June to March, (6) a size at first maturity around 300
      mm and (7) a diet composition of adults based mainly on fishes, and also on
      opportunistic behaviour in the food scarce environment of deep waters. The
      results suggest that the species' distribution and feeding strategies are the
      most appropriate for the oligotrophic eastern Ionian waters and that these
      conditions result in smaller sizes of the species in the east Mediterranean Sea
      compared to the west basin and the east Atlantic Ocean, with implications for the
      growth and reproductive biology of the species. 

PMID- 24298952
TI  - Proliferation of elongate fishes in the deep sea.
AB  - It was hypothesized that energetically efficient anguilliform swimming and axial
      elongation in fishes is favoured in the deep sea and predicted that the degree of
      elongation of the body form of fishes would increase with depth. An index of fish
      shape was derived from the relationship between length and mass. This was
      combined with data on abundance of c. 266 fish species from 389 research trawl
      tows made at depths of between 300 and 2030 m in the north-east Atlantic Ocean.
      The degree of elongation of the fish increased with depth to c. 1250 m before
      levelling off. The strength of this phenomenon varied between higher level taxa,
      being most apparent in the Gadiformes and Osmeriformes, and weak or absent in the
      Perciformes and Selachimorpha. The advantage of efficient elongate body forms may
      explain why certain taxa such as the grenadiers (Macrouridae) have dominated the
      deep sea, some have restricted depth ranges, e.g. the sharks, skates and rays,
      and others are almost entirely absent, e.g. the flatfishes (Pleuronectiformes). 

PMID- 24298953
TI  - Red muscle proportions and enzyme activities in deep-sea demersal fishes.
AB  - Owing to the paucity of data on the red muscle of deep-sea fishes, the goal of
      this study was to determine the proportions of red muscle in demersal fishes and
      its enzymatic activities to characterize how routine swimming abilities change
      with depths of occurrence. Cross sectional analysis of the trunk musculature was
      used to evaluate the proportion of red muscle in 38 species of Californian
      demersal fishes living at depths between 100 and 3000 m. The activity of
      metabolic enzymes was also assayed in a sub-set of 18 species. Benthic fishes had
      lower proportions of red muscle and lower metabolic enzyme activities than
      benthopelagic species. Mean proportion of red muscle declined significantly with
      depth with the greatest range of values in shallow waters and species with low
      proportions found at all depths. This suggested that while sedentary species
      occur at all depths, the most active species occur in shallow waters. Citrate
      synthase activity declined significantly with depth across all species,
      indicating that the mass-specific metabolic capacity of red muscle is lower in
      deep-sea species. These patterns may be explained by coupling of red and white
      muscle physiologies, a decrease in physical energy of the environment with depth
      or by the prevalence of anguilliform body forms and swimming modes in deep-living
      species. 

PMID- 24298954
TI  - Thermal, trophic and metabolic life histories of inaccessible fishes revealed
      from stable-isotope analyses: a case study using orange roughy Hoplostethus
      atlanticus.
AB  - A time-resolved record of inhabited water depth, metabolic rate and trophic
      behaviour of the orange roughy Hoplostethus atlanticus was recovered from
      combined stable-isotope analyses of otolith and muscle tissue. The results
      demonstrate that H. atlanticus from the north-east Atlantic Ocean have a complex
      life history with three distinct depth-stratified life stages. Early juvenile H.
      atlanticus occupy relatively shallow habitats, juvenile H. atlanticus show a deep
      demersal phase, rising at sexual maturity, and adult H. atlanticus exploit
      increasingly deep habitats with increasing age. At all sampled sizes, H.
      atlanticus muscle tissues have an isotopic composition suggesting a benthic
      rather than benthopelagic or pelagic diet. Isotopic measures of relative
      metabolic rate provide an insight into energy partitioning throughout ontogeny.
      Hoplostethus atlanticus have relatively low metabolic rates compared to
      coexisting deep-water benthic fishes, consistent with their unusually high
      longevity. Surprisingly, lifetime fastest growth rates are achieved during
      juvenile stages when otolith isotopes imply deep-water residency and relatively
      low metabolic rates. Fast growth may be sustained during a period of high
      efficiency associated with reduced metabolic costs of prey capture or predator
      evasion. The stable-isotope approach can be applied to any teleost and provides a
      rapid, cost-effective technique for studying deep-water fish communities. 

PMID- 24298955
TI  - Diet and feeding strategy of blackmouth catshark Galeus melastomus.
AB  - Diet and feeding strategy of the blackmouth catshark Galeus melastomus in the
      deep waters of the eastern Ionian Sea were investigated. Sampling was carried out
      using experimental bottom longline fishing at depths ranging from 300 to 855 m in
      summer and autumn 2010. Diet variability with fish size, season, area, sex and
      depth zone was tested and only season was found to significantly affect the diet
      of the species. Of the 870 stomachs examined, only 1.4% were empty. Cumulative
      prey curves showed that the sample sizes were adequate to describe the main prey
      items of the diet for both seasons. Prey identified belonged primarily to three
      major groups: fishes, cephalopods and dendrobranchiatan and caridean shrimps. In
      autumn, the above three major groups were found as principal prey, whereas in
      summer cephalopods followed by fishes were the principal prey and shrimps were
      found as secondary prey. SIMPER analysis indicated high dissimilarity between
      seasons and highlighted that Sepiolidae, Myctophidae, fishes, cephalopods,
      shrimps and other crustaceans contributed to seasonal differences in the diet of
      G. melastomus. The prey diversity index was higher in autumn than in summer. A
      high dietary overlap was observed between the two seasons. Galeus melastomus
      behaved as an opportunistic predator with a variety of unimportant prey in its
      diet. Feeding strategy indicated that G. melastomus holds a generalist niche with
      a considerable specialization at the individual level. This strategy seems to be
      an adaptation to a food-scarce environment, as typified in deep-water habitats. 

PMID- 24298956
TI  - Fetal umbilical artery Doppler pulsatility index as a predictor of cardiovascular
      risk factors in children--a long-term follow up study.
AB  - Abstract Objective: To determine if high umbilical artery Doppler (UAD)
      pulsatility index (PI) is associated with cardio-vascular (CV) risk-factors in
      children at age 12 years. METHODS: We studied 195 children at age 12 years who
      had had in-utero UAD studies performed at 28 weeks' gestation. The children were
      grouped according to whether their umbilical Doppler PI was high (indicating poor
      feto-placental circulation) or normal. At age 12 years we assessed CV risk
      factors, including anthropometric measures, blood pressure, pulse wave velocity
      (a measure of arterial compliance), cardio-respiratory fitness, and homocysteine
      and cholesterol serum levels. RESULTS: Compared with children with a normal UAD
      PI (N = 88), the children (N = 107) with high UAD PI had higher resting pulse
      rate (p = 0.04), higher pulse wave velocity (p = 0.046), higher serum
      homocysteine levels (p = 0.032) and reduced arterial compliance (7.58 versus 8.50
      m/s, p = 0.029) using univariate analysis. These differences were not present
      when adjusting for cofounders was modeled. CONCLUSION: High PI on UAD testing in
      utero may be associated with increased likelihood of some CV risk factors at age
      12-years but confounding variables may be as important. Our study raises possible
      long-term benefits of in-utero UAD measurements.

PMID- 24298957
TI  - Point-of-care syndrome-based, rapid diagnosis of infections on commercial ships.
AB  - BACKGROUND: Suspicion of contagious disease on commercial ships tends to be
      poorly managed, as there is little capacity to confirm a case on board except for
      malaria. Here we implemented a point-of-care (POC) laboratory on one container
      ship and one cruise ship for the rapid syndrome-based diagnosis of infectious
      diseases on board. METHODS: In 2012 we implemented a POC laboratory on board a
      freight ship and on board a cruise ship. The POC laboratory ran a total of six
      different color-coded, syndrome-based kits incorporating 10 different
      commercially available immunochromatographic tests. The POC tests were taught
      within 1-hour as part of training to staff without any previous knowledge in
      microbiology. RESULTS: Compared with terrestrial POCs, specific constraints
      included the necessity to secure POC devices into the motile ship, to use robust
      devices, to overcome difficulties in communicating with the core laboratory, and
      to overcome limited intimacy of patients. However, a total of 36 POC tests were
      easily performed and yielded contributive negative results. CONCLUSIONS: This
      first experiment indicates that it is possible to run POC laboratories by
      nonexpert staff after providing rapid teaching course on board commercial ships.
      Generalization of on-board POC laboratories is expected to help in improving the
      medical management of staff and passengers.

PMID- 24298958
TI  - [The evaluation of asthma and COPD awareness in Turkey (GARD Turkey Project
      National Control Program of Chronic Airway Diseases)].
AB  - INTRODUCTION: Although chronic respiratory disorders are important causes of
      morbidity and mortality, health care workers, patients and caretakers are not
      well informed about these disorders. Therefore these problems are underdiagnosed
      and undertreated; also preventive measures are not widely taken. Our aim was to
      evaluate the knowledge of asthma and chronic obstructive pulmonary disease (COPD)
      in Turkey. This study was designed and performed as a Global Alliance Against
      Respiratory Disorders (GARD) project. MATERIALS AND METHODS: People greater than
      15 years of age who lived in cities with a population of 200 or greater were
      eligible for the study. A questionnaire including demographic data and questions
      regarding asthma and COPD was used for the evalution of the participants.
      RESULTS: 12.000 people were selected (6000 in rural and 6000 in urban areas);
      8527 people were reached. 8342 people who completed the questionnaire were
      included to the study. There were 4182 (50.1%) female and 4160 (%49.9) male
      subjects. 49.6% of the subjcets knew that COPD is a lung disease, 51.1% indicated
      that smoking is the most important risk factor for COPD and 48% identified
      quitting smoking as the most important preventive measure. Every other person had
      baseline knowledge on COPD. However only 25.2% knew that there are treatment
      options for COPD. 80% of subjects said astma can be seen in all age groups. 51.1%
      knew asthma is a genetic disease and 58% said it is not an infectious disease.
      However when whether asthma medications caused drug dependency only 27% answered
      as "No" while 55.2% said "They do not know". CONCLUSION: Awareness of COPD and
      asthma seem to be infsufficient among Turkish people. Since these disorders are
      important causes of morbidity and mortality and have high impact on work and
      economic loss, it is important to increase knowledge among public.

PMID- 24298959
TI  - The knowledge and considerations of the physicians regarding the inhaler devices
      in asthma and COPD: the INTEDA-1 study.
AB  - INTRODUCTION: The present paper was aimed at indicating and discussing the
      possible problems related to inhaler devices by considering the knowledge and
      practices of the physicians regarding the inhalation therapies. MATERIALS AND
      METHODS: The present study is a prospective, cross-sectional survey carried out
      by Turkish Respiratory Society Inhalation Therapy Group between February 2010 and
      February 2011 with a participation of ten individual centres. Seven inhaler
      devices that were available on the market in the country were assessed. The data
      on the problems that 684 clinicians actively attending patients with respiratory
      disorders experienced in daily clinical practice or their evaluations of their
      patients were obtained through the questionnaire. RESULTS: The respondents, most
      of whom were pulmonologist (37.5%), and pediatrist (38.1%), had been,on average,
      11.6 years in profession. The source of information on inhalers and
      administration techniques were reported to be mainly the internet and patient
      leaflets. Of the participants only 18.5% reported to have had adequate knowledge
      of inhaler devices and proper administration techniques. Most of the participants
      stated that they themselves provided the instructions of administration and that
      the method was often verbal explanation. The physicians believed that although
      approximately 60% of the patients used the drug correctly, 40.7% made critical
      mistakes to have adverse effects on the therapeutic outcome. The most important
      criteria on which the physians lay greater emphasis in choosing the inhaler
      devices were the physical capability, skills and age of the patients. CONCLUSION:
      The awareness of proper use of inhaler devices is a fundamental prerequisite for
      effective inhalation therapy has been improved in physicians. The results of the
      present study have shown that more effort is required for professional training.
      Assisting the physicans with medical personnel for training of the patients and
      educational motivation are required.

PMID- 24298960
TI  - [Effects of COPD on cognitive functions: a case control study].
AB  - INTRODUCTION: Assessment of disease severity, effects of disease on health status
      and future events should be considered to direct treatment strategies in chronic
      obstructive pulmonary disease (COPD) management. Although extrapulmonary effects
      of COPD are well known, effects of COPD on cognitive functions have not been
      evaluated sufficiently. therefore we aimed to determine cognitive functions of
      copd patients in the present study. MATERIALS AND METHODS: 112 COPD patients with
      moderate, severe and very severe irreversible airway obstruction and 44 age
      matched healthy subjects without COPD and systemic diseases as control group were
      enrolled to the study. Mini mental state examination (MMSE) was performed to
      evaluate cognitive functions. MMSE results were compared between patient and
      control groups. Moreover relationship between exacerbation frequency and
      cognitive functions was evaluated. RESULTS: Total 156 subjects as 112 COPD
      patients and 44 healthy subjects were included to the study. Mean age of COPD
      patients was 65.03 +/- 7.63 years, and mean age of control group was 63.63 +/-
      8.96 years (p= 0.364). Mean score of MMSE in COPD patients was 23.8 +/- 4.39, and
      mean score of MMSE in control group was 26.7 +/- 2.88. We determined a
      significant difference in terms of MMSE scores betweeen patient and control group
      (p< 0.0001). MMSE scores and FEV1 values were significantly different among
      patients with moderate, sevre and very severe airflow obstruction (p= 0.001; p<
      0.0001 respectively). We found a significant negative correlation between MMSE
      results and exacerbation frequency during last year (p= 0.003; r= -0.239).
      CONCLUSION: Lower MMSE scores of COPD patients than subjects in control group
      indicates the impairment of cognitive functions in COPD patients. Moreover a
      negative relationship between MMSE scores with exacerbation frequency during last
      year suggests that prevention from exacerbation can decrease cognitive impairment
      in COPD patients. We believe that assessment of cognitive functions and
      preventive strategies should be considered in COPD management.

PMID- 24298961
TI  - [Investigation of CCL1 rs159294 T/A gene polymorphism in pulmonary and
      extrapulmonary tuberculosis patients].
AB  - INTRODUCTION: The purpose of this study is to reveal whether CCL1 rs159294 T/A
      polymorphism in pulmonary and extrapulmonary tuberculosis patients pose a risk to
      catch tuberculosis or not. MATERIALS AND METHODS: In the study, peripheral blood
      samples from the control group, which includes 160 patients, who consulted to
      Firat University Faculty of Medicine, Pulmonology Policlinic in Elazig province
      and who were diagnosed with tuberculosis; and 160 healthy individuals, were taken
      and put into tubes containing EDTA. Each tube contained 2 cc blood samples. DNA
      isolation was made from these blood samples and CCL1 rs159294 T/A polymorphism
      was defined with PCR-RFLP analysis. RESULTS: For CCL1 rs159294 T/A polymorphism,
      TT genotype was found in 98 (61.3%) patients, TA genotype was found in 58 (36.3%)
      patients, AA genotype was found in 4 (2.5%) patients among 160 patients with
      tuberculosis; and TT genotype was found in 50 (70.4%) patients, TA genotype in 20
      (28.2%) patients, AA genotype was found in 1 (1.4%) patient among 71 patients
      with pulmonary tuberculosis; TT genotype was found in 48 (53.9%) patients TA
      genotype was found in 38 (42.7%) patients and AA genotype was found in 3 (3.4%)
      patients among 89 extrapulmonary tuberculosis patients. And in control group,
      among 160 healthy individuals, TT genotype was found in 100 (62.5%) individuals,
      TA genotype was found in 58 (36.3%) individuals, AA genotype was found in 2
      (1.3%) individuals and no statistically significant difference was found.
      CONCLUSION: CCL1 rs159294 T/A polymorphism do not form an inclination to
      tuberculosis in our population.

PMID- 24298962
TI  - [The prevalence of chronic bronchitis in adults living in the center of
      Gumushane].
AB  - INTRODUCTION: Chronic bronchitis and emphysema are major components of chronic
      obstructive pulmonary diseases (COPD). The aim of this study was to determine the
      prevalence of chronic bronchitis 20 years and over living in the center of
      Gumushane and to analyze the risk factors. MATERIALS AND METHODS: The study is
      targeted to reach 373 people who represent the center of Gumushane, 368 (98.6%)
      people have been reached. Participants were filled modified version of the
      questionnaire created by the Medical Research Council by face-to-face interview
      technique. RESULTS: The prevalence of chronic bronchitis was 14.1%. The average
      age was in the chronic bronchitis group and non-chronic bronchitis group was
      respectively 43.2 +/- 12.9, 39.3 +/- 11.6, and the differance was statistically
      significant (p< 0.05). Considering the relationship between cigarette smoking
      with chronic bronchitis, it was more frequent in smokers than non-smokers (p<
      0.001, OR 4.74, 95% CI 2.47-9.17). Chronic bronchitis was observed in passive
      smokers than in non-smokers (p= 0.004, OR 2.86, 95% CI 1.36-6.03). Occupational
      exposure to dust, fumes and history of childhood pulmonary diseases were
      increased chronic bronchitis prevalence (respectively, p< 0.001, OR 9.53, 95% CI
      4.56-19.94; p< 0.001, OR 12.14, 95% CI 5.87-25.12). Male gender, low income level
      and to warm up with stove were found statistically significant by univariate
      logistic regression analysis but these risk factors were not statistically
      significant in the multivariate analysis. Educational level was not found
      statistically significant in both analysis (p> 0.05). CONCLUSION: The prevalence
      of chronic bronchitis was 14.1% in 20 years and older adults living in the center
      of Gumushane. Old age (especially over the age of 50), active or passive smoking,
      occupational history of dust, fumes and history of childhood pulmonary diseases
      were found to be risk factors for chronic bronchitis.

PMID- 24298963
TI  - [Psychiatric evaluation in patients with obstructive sleep apnea syndrome].
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) might cause
      neuropsychiatric problems as well as cardiovascular and cerebrovascular
      complications. Daily life of the patients are effected and their quality of life
      decreases. In the present study, we aimed to evaluate anxiety and depression and
      to test their ability to cope with strees in patients with OSAS. MATERIALS AND
      METHODS: The patients with OSAS suspect admitting to our sleep laboratuary, were
      classed as simple snoring, mild-moderate and severe OSAS according to their apnea
      hypopnea index (AHI). Hospital anxiety and depression, stres coping and skill
      loss scales were applied to the patients accepted to participate to the study.
      RESULTS: Fifty four patients participated into the study. Forty-one (75.9%) were
      OSAS and 13 (24.1%) were simple snoring (control group). Mean age was 52.3 +/-
      9.2 years in OSAS group, while it was 50.5 +/- 9.9 years in control group.
      Snoring was found in every patient of two groups. Thirty-one (79.5%) patients
      with OSAS had witnessed apneas and 23 (60.5%) had exceesive OSAS patients had
      excessive daytime sleepiness. There was no significant differences in age, BMI,
      sleep efficency, HAD and skill loss scales between both groups. Autism was found
      higher in OSAS group with stres coping test (p= 0.031). Moreover, social support
      necessicity was found higher in moderate and severe OSAS patients. CONCLUSION: We
      found that neuropsyhiatric problems are highly seen in moderate and severe OUAS
      patients.

PMID- 24298964
TI  - Bronchial hyperresponsiveness in patients with obstructive sleep apnea syndrome.
AB  - INTRODUCTION: The relationship between obstructive sleep apnea syndrome (OSAS)
      and bronchial hyperresponsiveness (BHR) is not well known. In this study, we
      investigated the association between BHR and disease severity in patients with
      OSAS. MATERIALS AND METHODS: Fourty seven (37 male/10 female) OSAS patients
      admitted with polysomnography enrolled to the study. Histamine bronchial
      challenge test was performed and body mass index (BMI, kg/m2) was calculated.
      Presence of BHR was diagnosed as positivity of bronchial provocative test (BPT)
      (PD values <= 16 mg/mL). Patients were questioned with Epworth sleepiness scale
      (ESS). RESULTS: Histamine bronchial challenge test was positive in 21 of 47
      patients. There were significant negative correlations between PD 20 value and
      AHI (r= -0.47, p= 0.03), BMI (r= -0.45, p= 0.03), and ESS score (r= -0.45, p=
      0.03) in the patients with BHR. In addition, AHI (p= 0.03), BMI (p= 0.02), ESS
      scores (p= 0.03) were higher in patients with BHR (21 patients) than in patients
      not having BHR (26 patients). Significant negative relation was found between PD
      20 value and AHI (b=-0.45, p= 0.03) and significant positive relation was found
      between presence of BHR and AHI (p= 0.04), BMI (p= 0.03) independently of age and
      sex in multiple regression analysis. CONCLUSION: BHR is common in patients with
      OSAS. As severity of OSAS increased, severity of BHR increased. In addition,
      obesity may trigger presence of BHR in patients with OSAS.

PMID- 24298965
TI  - [The relationship between pulmonary function and exercise capacity and quality of
      life in patients with ankylosing spondylitis].
AB  - INTRODUCTION: Ankylosing spondylitis causes restrictive respiratory disorder by
      limiting the expansion of the chest because of the costosternal and
      costovertebral joints. Our study is planned to evaluate the respiratory functions
      of the ankylosing spondylitis patients who have a high rate of pulmonary
      involvement, and to compare the results with the exercise capacity and life
      quality of these patients. MATERIALS AND METHODS: There were 27 (18 male, 9
      female) Norvegian patients who came to Turkey and had ankylosing spondylitis
      diagnose according to Modified New York criterias, to have a routine physical
      therapy and rehabilitation programme with an average age of 50.6 +/- 6.6 years.
      The patients' clinical histories were taken. Pulmonary function tests were
      performed with spirometry and pulmonary muscle strength was measured with mouth
      pressure measure. 6 minute walk test was performed to determine exercise capacity
      and Short Form-36 Life Quality Questionairre was used to evaluate life quality of
      the patients. RESULTS: The patients had 18.85 +/- 10.64 average diagnose duration
      and the expected FEV1 value of the patients was 3.75 +/- 0.88 L/sec, FEV1/FVC
      ratio was 80.44 +/- 6.42, MIP was 62.96 +/- 20.61 and MEP was 80.22 +/- 21.12.
      40.7% of the patients had positive smoking history while 14.8 % had dyspnea and
      11.1% had symptoms of caughing-sputum. Walking distance was 595.50 +/- 83.20
      metre. Life quality category scores were 42.82 +/- 16.78 minimally, 83.58 +/-
      23.06 maximally. Pulmonary function and pulmonary muscle strength values were
      similar in smoking and non-smoking patients. But in smoking patients, physical
      function and social function categories of quality of life survey scores were
      found lower than non-smoking patients. CONCLUSION: Respiratory and other
      parameters were high related to high standarts in treatment and following and
      exercise habit of the patients in Norway. Accordingly, it is thought that an
      appropriate medical treatment and exercise as a lifestyle habits of the patients
      reduce the negative effects of ankylosing spondylitis on respiratory system.

PMID- 24298966
TI  - Clinical course of community-acquired respiratory syncytial virus pneumonia in
      newborns hospitalized in neonatal intensive care unit.
AB  - INTRODUCTION: Respiratory syncytial virus (RSV) is a major cause of pneumonia in
      infants worldwide. We aimed to evaluate the clinical course of community-acquired
      RSV pneumonia in newborns hospitalized in neonatal intensive care unit. MATERIALS
      AND METHODS: All the newborns diagnosed as pneumonia were prospectively evaluated
      for RSV infection between November 2010 and April 2011. Fifty-four specimens of
      nasopharyngeal secretions were tested in parallel with the RAT and the multiplex
      real time polymerase chain reaction (RT- PCR). Downes' score was used to assess
      the disease severity in patients with pneumonia. RESULTS: RAT has a sensitivity
      of 90% and a specificity of 78.5%, as the PCR technique target assay. Four of the
      patients with RSV pneumonia had secundum atrial septal defect (ASD) and all of
      four needed mechanical ventilation support. The first day Downes' score was
      positively correlated with time of intravenous fluid requirement (p= 0.001, r=
      0.48), total oxygen need (p= 0.000, r= 0.63), and re-enteral feeding (p= 0.001,
      r= 0.46). Blood pH (p= 0.031, r= 0.46) were negatively correlated with Downes'
      score. The second day Downes' score was higher in patients with ASD than those of
      without ASD (3.8 +/- 2.6 vs. 2 +/- 1.1, p= 0.01). The most possible risk factor
      for longer hospital stay was the higher second day Downes' score (p= 0.02 OR:
      1.9, CI 95% (1.1-3.2). All infants were discharged from hospital in a good
      health. CONCLUSION: RAT is sensitive and specific in detecting RSV infections in
      newborns. Physicians may use Downes' score for evaluation of disease severity in
      infants with RSV pneumonia. In these patients, ASD has increased the disease
      severity.

PMID- 24298967
TI  - Obstructive sleep apnea and asthma: is it just a matter of CPAP.

PMID- 24298968
TI  - Miliary tuberculosis after intravesical Bacillus Calmette-Guerin immunotherapy.

PMID- 24298969
TI  - [Progress of treatment delayed testicular tuberculosis: one case].

PMID- 24298970
TI  - A case of pulmonary alveolar microlithiasis with Sjogren's syndrome.

PMID- 24298971
TI  - Minimal invasive approachs for intrathoracic benign disease.

PMID- 24298972
TI  - Mechanical bronchodilatation for asthmatic airway: role of CPAP therapy.

PMID- 24298973
TI  - Adrenal mass mimicking the incidentaloma in a patient with newly diagnosed
      adrenal failure due to tuberculosis.

PMID- 24298974
TI  - Postnatal oral hydrocortisone in treatment of bronchopulmonary dysplasia: an
      observational study.
AB  - INTRODUCTION: The aim of our study was to determine whether hydrocortisone even
      at low dose could be an effective and safe alternative treatment for
      bronchopulmonary dysplasia. MATERIALS AND METHODS: This prospective pilot study
      was conducted in a tertiary referral neonatal intensive care unit placed in
      Ankara Zekai Tahir Burak Maternity Teaching Hospital. Preterm babies (> 32 week
      gestational age or > 1500 g birth weight) who were ventilator dependent
      approximately at or beyond three weeks of age (defined as rescue treatment) or
      were oxygen dependent on postmenstrual 36th week without evidence of any
      infection (defined as bronchopulmonary dysplasia treatment) were enrolled in the
      study. Hydrocortisone was used orally in an initial dose of 1 mg/kg twice a daily
      for a week and then the dose was tapered by 10-20% every other day regarding to
      clinical response. RESULTS: A total of 90 infants were enrolled in this study.
      After hydrocortisone treatment only 3 (3.4%) patients were still on respiratory
      support. When safety of the drug was evaluated 8 (8.8%) infants had early
      complications of hydrocortisone treatment. CONCLUSION: To the best of our
      knowledge this study is the first trial in the literature along with the
      hydrocortisone dose and the initiation time in treatment of bronchopulmonary
      displasia.

PMID- 24298975
TI  - Source identification and apportionment of halogenated compounds observed at a
      remote site in East Asia.
AB  - The sources of halogenated compounds in East Asia associated with stratospheric
      ozone depletion and climate change are relatively poorly understood. High
      precision in situ measurements of 18 halogenated compounds and carbonyl sulfide
      (COS) made at Gosan, Jeju Island, Korea, from November 2007 to December 2011 were
      analyzed by a positive matrix factorization (PMF). Seven major industrial sources
      were identified from the enhanced concentrations of halogenated compounds
      observed at Gosan and corresponding concentration-based source contributions were
      also suggested: primary aluminum production explaining 37% of total concentration
      enhancements, solvent usage of which source apportionment is 25%, fugitive
      emissions from HCFC/HFC production with 11%, refrigerant replacements (9%),
      semiconductor/electronics industry (9%), foam blowing agents (6%), and fumigation
      (3%). Statistical trajectory analysis was applied to specify the potential
      emission regions for seven sources using back trajectories. Primary aluminum
      production, solvent usage and fugitive emission sources were mainly contributed
      by China. Semiconductor/electronics sources were dominantly located in Korea.
      Refrigerant replacement, fumigation and foam blowing agent sources were spread
      throughout East Asian countries. The specified potential source regions are
      consistent with country-based consumptions and emission patterns, verifying the
      PMF analysis results. The industry-based emission sources of halogenated
      compounds identified in this study help improve our understanding of the East
      Asian countries' industrial contributions to halogenated compound emissions. 

PMID- 24298976
TI  - Alterations in the predicted regulatory and coding regions of the sterol 14alpha
      demethylase gene (CYP51) confer decreased azole sensitivity in the oilseed rape
      pathogen Pyrenopeziza brassicae.
AB  - The incidence and severity of light leaf spot epidemics caused by the ascomycete
      fungus Pyrenopeziza brassicae on UK oilseed rape crops are increasing. The
      disease is currently controlled by a combination of host resistance, cultural
      practices and fungicide applications. We report decreases in sensitivity of
      modern UK P. brassicae isolates to the azole (imidazole and triazole) class of
      fungicides. By cloning and sequencing the P. brassicae CYP51 (PbCYP51) gene,
      encoding the azole target sterol 14alpha-demethylase, we identified two non
      synonymous mutations encoding substitutions G460S and S508T associated with
      reduced azole sensitivity. We confirmed the impact of the encoded PbCYP51 changes
      on azole sensitivity and protein activity by heterologous expression in a
      Saccharomyces cerevisiae mutant YUG37:erg11 carrying a controllable promoter of
      native CYP51 expression. In addition, we identified insertions in the predicted
      regulatory regions of PbCYP51 in isolates with reduced azole sensitivity. The
      presence of these insertions was associated with enhanced transcription of
      PbCYP51 in response to subinhibitory concentrations of the azole fungicide
      tebuconazole. Genetic analysis of in vitro crosses of sensitive and resistant
      isolates confirmed the impact of PbCYP51 alterations in coding and regulatory
      sequences on a reduced sensitivity phenotype, as well as identifying a second
      major gene at another locus contributing to resistance in some isolates. The
      least sensitive field isolates carry combinations of upstream insertions and non
      synonymous mutations, suggesting that PbCYP51 evolution is ongoing and the
      progressive decline in azole sensitivity of UK P. brassicae populations will
      continue. The implications for the future control of light leaf spot are
      discussed. 

PMID- 24298978
TI  - Palladium-catalyzed cross-coupling of N-sulfonylaziridines with boronic acids.
AB  - A mild palladium-catalyzed cross-coupling of unsubstituted and 2-alkyl
      substituted aziridines with arylboronic acid nucleophiles is presented. The
      reaction is highly regioselective and compatible with diverse functionality. A
      catalytic amount of base, a sterically demanding triarylphosphine ligand, and a
      phenol additive are critical to the success of the reaction. Coupling of a
      deuterium-labeled substrate established that ring opening of the aziridine occurs
      with inversion of stereochemistry. 

PMID- 24298977
TI  - Impact of fetal development on neurocognitive performance of adolescents with
      cyanotic and acyanotic congenital heart disease.
AB  - BACKGROUND: Our aims were to evaluate the neurocognitive performance in
      adolescents with congenital heart disease (CHD) and to determine whether
      parameters of fetal development evaluated in neonates, such as head
      circumference, length, weight, and Apgar scores, are somehow related to their
      neurocognitive performance. METHODS: We evaluated 77 CHD patients (43 males) aged
      from 13 to 18 years old (mean = 15.04 +/- 1.86), 46 cyanotic, 23 with tetralogy
      of Fallot (TF), 23 with transposition of the great arteries (TGA) and 31
      acyanotic with ventricular septal defect (VSD) enrolled in this study. The
      control group included 16 healthy children (11 males) ages ranging from 13 to 18
      years old (mean = 15.69 years +/- 1.44 years). All assessment measures for CHD
      patients were once obtained in a tertiary hospital; the control group was
      evaluated in school. Neuropsychological assessment included Wechsler's Digit
      Test, direct and reverse (WDD and WDR) and Symbol Search, Rey's Complex Figure
      (RCF), BADS's Key Searching Test, Color-Word Stroop Test (CWS), Trail Making Test
      (TMT), and Logical Memory Task (LMT). We evaluated some fetal parameters, such as
      head circumference, weight and length assessed at birth, and neonatal parameters,
      such as Apgar scores at 1 and 5 minutes after birth. We also registered some
      surgical parameters, such as the age at first operation and the number of
      surgeries. RESULTS: CHD patients compared with control group showed lower scores
      on every test, except for logical memory task. Patients with VSD when compared
      with patients with TF and TGA showed better results in all neuropsychological
      tests, although the only significant differences were in RCF, copy (F = 4936; P =
      .010). Several correlations were apparent between fetal/neonatal parameters and
      neuropsychological abilities in each type of CHD. However, head circumference at
      birth stands as the main correlation with cognitive development later on in all
      kinds of CHD (WDD: rho = .339, P = .011; RCF, copy: rho = 0.297, P = .027; CWS,
      interference: rho = 0.283, P = .036; TMT-A: rho = -0.321, P = .017). We analyzed
      the predicting relevance of several variables to cognitive performance of
      adolescents with CHD and confirmed that "cyanosis" stands as the main predictor
      (a = -4.758; t = -2.622; P = .011). CONCLUSIONS: Adolescents with CHD have worse
      neuropsychological performance than the control group, mainly the cyanotic
      patients. Fetal circulation seems to have impact on cerebral and somatic growth,
      predicting cognitive impairment in adolescents with CHD.

PMID- 24298979
TI  - Effect of the pro-resolution lipid mediator Resolvin E1 (RvE1) on pulp tissues
      exposed to the oral environment.
AB  - AIM: To evaluate the effects of topical Resolvin E1 (RvE1) application on
      infected dental pulps. METHODOLOGY: Forty-two male Wistar rats (n = 6 per three
      groups/and two time periods) were used. To induce inflammation, pulps in
      mandibular right first molars were accessed and then left exposed to the oral
      environment for 24 h. After this period, topical medication with a
      corticosteroid/antibiotic blend, or RvE1, or its vehicle (Ethanol 0.1%) was
      directly applied onto the pulp tissue and teeth were restored with silver
      amalgam. The effects of the protocols were evaluated histologically and compared
      with control pulps not exposed to the oral environment. The inflammatory changes
      after 24 and 72 h were assessed through a scoring method and analysed using the
      Kruskal-Wallis test followed by Dunn's. Differences were considered significant
      if P < 0.05 (CI = 95%). RESULTS: Ethanol and corticosteroid/antibiotic treatment
      were not effective in arresting severe inflammatory alterations of exposed pulps
      at 24 and 72 h (P < 0.05, CI = 95%). At both time periods, RvE1 treatment led to
      a reduction of tissue cellularity and extent of inflammation, whose changes were
      not different from control pulps (P > 0.05, CI = 95%). CONCLUSIONS: A protective
      role for RvE1 in pulp inflammation was observed even in the presence of
      contamination, suggesting that it may be a candidate for a novel therapeutic
      strategy for conservative dental pulp treatment.

PMID- 24298980
TI  - T cells from chronic bone infection show reduced proliferation and a high
      proportion of CD28- CD4 T cells.
AB  - Chronic bone infection is associated with bone resorption. From animal studies,
      CD3/CD28-activated T cells are known to enhance osteoclastogenesis and bone
      resorption. Because CD28 is expressed constitutively on T cells and its
      expression is down-regulated by chronic exposure to the inflammatory environment,
      we characterized co-stimulatory molecule expression on T cells from chronically
      infected patients. We used cytofluorometric techniques to phenotypically
      characterize T cells, its co-stimulatory molecules and perforin secretion from
      infected and non-infected human bones. Chronic bone infection was defined as
      infection lasting for more than a month. We show a higher T cell activation
      [human leucocyte antigen D-related (HLA-DR+)] in infected compared to non
      infected bones: median being 16 versus 7%, P = 0.009 for CD4 T cells, and 33
      versus 15%, P = 0.038 for CD8 T cells, respectively. However, T cell
      proliferation (Ki67+) was lower for CD8 T cells in infected bones: 26 versus 34%,
      P = 0.045. In contrast, we detected no difference in apoptosis and regulatory T
      cells. In infected bone, we found higher CD28-negative CD4+ T cells compared to
      non-infected bone: 20 versus 8%, respectively (P = 0.005); this T cell subset had
      higher CD11b expression and perforin secretion. Chronically infected human bones
      are characterized by an increase of CD28-negative CD4+ T cells, indicating long
      term activated cells with cytotoxic ability. Therefore, this alteration of co
      stimulatory molecules may modify interactions with osteoclasts and impact bone
      resorption.

PMID- 24298981
TI  - Chemical composition and insecticidal activity of plant essential oils from Benin
      against Anopheles gambiae (Giles).
AB  - BACKGROUND: Insecticide resistance in sub-Saharan Africa and especially in Benin
      is a major public health issue hindering the control of the malaria vectors. Each
      Anopheles species has developed a resistance to one or several classes of the
      insecticides currently in use in the field. Therefore, it is urgent to find
      alternative compounds to conquer the vector. In this study, the efficacies of
      essential oils of nine plant species, which are traditionally used to avoid
      mosquito bites in Benin, were investigated. METHODS: Essential oils of nine plant
      species were extracted by hydrodistillation, and their chemical compositions were
      identified by GC-MS. These oils were tested on susceptible "kisumu" and resistant
      "ladji-Cotonou" strains of Anopheles gambiae, following WHO test procedures for
      insecticide resistance monitoring in malaria vector mosquitoes. RESULTS:
      Different chemical compositions were obtained from the essential oils of the
      plant species. The major constituents identified were as follows: neral and
      geranial for Cymbopogon citratus, Z-carveol, E-p-mentha-1(7),8-dien-2-ol and E-p
      mentha-2,8-dienol for Cymbopogon giganteus, piperitone for Cymbopogon
      schoenanthus, citronellal and citronellol for Eucalyptus citriodora, p-cymene,
      caryophyllene oxide and spathulenol for Eucalyptus tereticornis, 3-tetradecanone
      for Cochlospermum tinctorium and Cochlospermum planchonii, methyl salicylate for
      Securidaca longepedunculata and ascaridole for Chenopodium ambrosioides. The
      diagnostic dose was 0.77% for C. citratus, 2.80% for E. tereticornis, 3.37% for
      E. citriodora, 4.26% for C. ambrosioides, 5.48% for C. schoenanthus and 7.36% for
      C. giganteus. The highest diagnostic doses were obtained with S. longepedunculata
      (9.84%), C. tinctorium (11.56%) and C. planchonii (15.22%), compared to
      permethrin 0.75%. A. gambiae cotonou, which is resistant to pyrethroids, showed
      significant tolerance to essential oils from C. tinctorium and S.
      longepedunculata as expected but was highly susceptible to all the other
      essential oils at the diagnostic dose. CONCLUSIONS: C. citratus, E. tereticornis,
      E. citriodora, C. ambrosioides and C. schoenanthus are potential promising plant
      sources for alternative compounds to pyrethroids, for the control of the
      Anopheles malaria vector in Benin. The efficacy of their essential oils is
      possibly based on their chemical compositions in which major and/or minor
      compounds have reported insecticidal activities on various pests and disease
      vectors such as Anopheles.

PMID- 24298982
TI  - A prospective, randomized, controlled study using OsseoSpeedTM implants placed in
      maxillary fresh extraction socket: soft tissues response.
AB  - PURPOSE: The aim of this work was to study the peri-implant soft tissues
      response, by evaluating both the recession and the papilla indexes, of patients
      treated with implants with two different configurations. In addition, data were
      stratified by tooth category, smoking habit and thickness of buccal bone wall.
      MATERIALS AND METHODS: The clinical trial was designed as a prospective,
      randomized-controlled multicenter study. Adults in need of one or more implants
      replacing teeth to be removed in the maxilla within the region 15-25 were
      recruited. Following tooth extraction, the site was randomly allocated to receive
      either a cylindrical or conical/cylindrical implant. The following parameters
      were studied: (i) Soft tissue recession (REC) measured by comparing the gingival
      zenith (GZ) score at baseline (permanent restoration) with that of the yearly
      follow-up visits over a period of 3 years (V1, V2 and V3). (ii) Interdental
      Papilla Index (PI): PI measurements were performed at baseline and compared with
      that of the follow-up visits. In addition, data were stratified by different
      variables: tooth category: anterior (incisors and canine) and posterior (first
      and second premolar); smoking habit: patient smoker (habitual or occasional
      smoker at inclusion) or non-smoker (non-smoker or ex-smoker at inclusion) and
      thickness of buccal bone wall (TB): TB <= 1 mm (thin buccal wall) or TB > 1 mm
      (thick buccal wall). RESULTS: A total of 93 patients were treated with 93
      implants. At the surgical re-entry one implant was mobile and then removed;
      moreover, one patient was lost to follow-up. Ninety-one patients were restored
      with 91 implant-supported permanent single crowns. After the 3-year follow-up, a
      mean gain of 0.23 mm of GZ was measured; moreover, 79% and 72% of mesial and
      distal papillae were classified as >50%/ complete, respectively. From the
      stratification analysis, not significant differences were found between the mean
      GZ scores of implants with TB <= 1 mm (thin buccal wall) and TB > 1 mm (thick
      buccal wall), respectively (P < 0.05, Mann-Whitney U-test) at baseline, at V1, V2
      and V3 follow-up visits. Also, the other variables did not seem to influence GZ
      changes over the follow-up period. Moreover, a re-growth of the interproximal
      mesial and distal papillae was the general trend observed independently from the
      variables studied. CONCLUSIONS: Immediate single implant treatment may be
      considered a predictable option regarding soft tissue stability over a period of
      3 years of follow-up. An overall buccal soft tissue stability was observed during
      the GZ changes from the baseline to the 3 years of follow-up with a mean GZ
      reduction of 0.23 mm. A nearly full papillary re-growth can be detectable over a
      minimum period of 2 years of follow-up for both cylindrical and
      conical/cylindrical implants. Both the interproximal papilla filling and the
      midfacial mucosa stability were not influenced by variables such as type of
      fixture configuration, tooth category, smoke habit, and thickness of buccal bone
      wall of <= 1 mm (thin buccal wall).

PMID- 24298984
TI  - Cerebellar abscess caused by Listeria monocytogenes in a liver transplant
      patient.
AB  - Brain abscesses are a rare but serious complication and have been documented in
      transplant recipients. Aspergillus is by far the most frequent etiology of post
      transplant brain abscesses. Bacteria, apart from Nocardia, have a low association
      with brain abscesses in transplant recipients. We report herein the case of a 52
      year-old man who had undergone orthotopic liver transplantation (OLT) for end
      stage liver disease and hepatocellular carcinoma secondary to chronic hepatitis,
      and who developed a cerebellar abscess (CA) from Listeria monocytogenes. Three
      months after transplantation, he presented with a 1-week history of headache and
      vomiting. Computed tomography scan of the brain revealed a space-occupying lesion
      in the right cerebellum, which was further confirmed by magnetic resonance
      imaging. Emergency surgery was planned because of pressure effect on the
      surrounding structures. The patient recovered smoothly from the surgery. To our
      knowledge, no reports of Listeria CA following OLT have been published in the
      English literature. This case shows that, although extremely rare, L.
      monocytogenes may cause CA in liver transplant recipients, and clinicians should
      be aware of this, so that prompt diagnosis and treatment can be instituted before
      serious brain damage can occur. 

PMID- 24298985
TI  - Leflunomide as part of the treatment for multidrug-resistant cytomegalovirus
      disease after lung transplantation: case report and review of the literature.
AB  - Treatment of cytomegalovirus (CMV) disease in transplant patients is challenging
      and, with antiviral resistance to first-line drugs, it remains uncertain which
      treatment algorithm to follow. Some data suggest that leflunomide, a pyrimidine
      synthesis inhibitor, can be used to treat resistant CMV infections. We report a
      57-year-old CMV immunoglobulin-G (IgG)-seronegative woman, who received a
      bilateral lung transplant (LuTx) from a CMV IgG-positive donor with CMV primary
      disease. The CMV strain was genotypically resistant to ganciclovir, foscarnet,
      and cidofovir. After starting leflunomide as add-on therapy to a multidrug anti
      CMV regimen, viral load declined substantially in 2 months without adverse
      events. This experience is discussed against the background of existing
      literature on the use of leflunomide as an anti-CMV agent in LuTx recipients.

PMID- 24298986
TI  - Successful treatment with fumagillin of the first pediatric case of digestive
      microsporidiosis in a liver-kidney transplant.
AB  - We report the first successful use, to our knowledge, of fumagillin alone in a
      pediatric patient to cure intestinal microsporidiosis in a liver-kidney
      transplanted child. Detection of Enterocytozoon bieneusi in stool became negative
      from the first post-therapeutic control, while digestive symptoms disappeared in
      4 days. During a 9-month follow-up, polymerase chain reaction and direct
      examinations remained negative for microsporidia in her feces. No major
      undesirable effects were noted during the anti-microsporidial therapy.

PMID- 24298987
TI  - Confirmation of cause and manner of death via a comprehensive cardiac autopsy
      including whole exome next-generation sequencing.
AB  - Annually, the sudden death of thousands of young people remains inadequately
      explained despite medicolegal investigation. Postmortem genetic testing for
      channelopathies/cardiomyopathies may illuminate a potential cardiac mechanism and
      establish a more accurate cause and manner of death and provide an actionable
      genetic marker to test surviving family members who may be at risk for a fatal
      arrhythmia. Whole exome sequencing allows for simultaneous genetic interrogation
      of an individual's entire estimated library of approximately 30000 genes.
      Following an inconclusive autopsy, whole exome sequencing and gene-specific
      surveillance of all known major cardiac channelopathy/cardiomyopathy genes (90
      total) were performed on autopsy blood-derived genomic DNA from a previously
      healthy 16-year-old adolescent female found deceased in her bedroom. Whole exome
      sequencing analysis revealed a R249Q-MYH7 mutation associated previously with
      familial hypertrophic cardiomyopathy, sudden death, and impaired beta-myosin
      heavy chain (MHC-beta) actin-translocating and actin-activated ATPase (adenosine
      triphosphatase) activity. Whole exome sequencing may be an efficient and cost
      effective approach to incorporate molecular studies into the conventional
      postmortem examination.

PMID- 24298988
TI  - Catheterization diastolic pressures correlate with diastolic dyssynchrony in
      patients with single right ventricles.
AB  - INTRODUCTION: Diastolic dyssynchrony has correlated with pulmonary capillary
      wedge pressures in patients with normal cardiac anatomy. No data exist in single
      right ventricle (sRV) patients. Goal of this study was to determine if diastolic
      dyssynchrony in sRV patients correlates with ventricular end-diastolic pressures
      (VEDP). METHODS: Tissue Doppler imaging (TDI) and strain rate (SR) analysis of
      sRV patients undergoing catheterization were performed. Time interval from onset
      of QRS to peak TDI e'-wave was obtained. Differences in intervals were
      calculated: QRS (RV) - QRS (IVS) and QRS (RV) - QRS (LV). Time interval from
      onset of QRS to peak strain rate early diastolic wave (SRe) was obtained for the
      6 segment model sRV. Standard deviation of the 6 SRe time intervals was
      calculated. Correlation of VEDP with timing intervals was analyzed. RESULTS:
      Forty sRV patients were evaluated. Age was 2.8 +/- 3.5 years. Catheterization
      VEDP of the sRV was 9.3 +/- 3.9 mmHg (median 8 mmHg range 4-24 mmHg). QRS (RV) -
      QRS (IVS) was 22.3 +/- 18.1 msec and QRS (RV) - QRS (LV) was 23.7 +/- 19.0 msec.
      SRe standard deviation of the sRV was 61.6 +/- 23.9 msec. There was no
      significant correlation with VEDP and QRS (RV) - QRS (IVS) (r = 0.1, P = NS) or
      with QRS (RV) - QRS (LV) (r = 0.2, P = NS). There was a significant correlation
      of VEDP with the SRe standard deviation value (r = 0.4, P < 0.05). CONCLUSION:
      Diastolic dyssynchrony correlated with VEDP in patients with sRV physiology.
      Future studies are needed to determine the significance of these findings.

PMID- 24298990
TI  - Introduction. Evidence-based Guidelines for prehospital practice: a process whose
      time has come.

PMID- 24298991
TI  - Stimulated emission properties of fluorophores by CW-STED single molecule
      spectroscopy.
AB  - Fluorophores useful for STimulated Emission Depletion (STED) spectroscopy must
      fulfill strict requirements on depletion efficiency and photostability. These
      parameters determine the effective resolution of STED imaging. Resolution is
      typically measured on 30-80 nm spheres heavily decorated with STED bright
      fluorophores, limiting the possibility to estimate the true resolution achievable
      on a specific dye. Here we show how single molecule STED microscopy provides an
      estimate of the fluorophore stimulated emission cross section and of its
      photostability under STED irradiation. Fluorescein, a green and a yellow mutant
      of GFP, are tested, and the results are discussed and compared to those obtained
      with Chromeo488-covered 80 nm spheres on a commercial continuous-wave STED
      microscope. 

PMID- 24298989
TI  - Parkin reverses TDP-43-induced cell death and failure of amino acid homeostasis.
AB  - The E3 ubiquitin ligase Parkin plays a central role in the pathogenesis of many
      neurodegenerative diseases. Parkin promotes specific ubiquitination and affects
      the localization of transactivation response DNA-binding protein 43 (TDP-43),
      which controls the translation of thousands of mRNAs. Here we tested the effects
      of lentiviral Parkin and TDP-43 expression on amino acid metabolism in the rat
      motor cortex using high frequency 13C NMR spectroscopy. TDP-43 expression
      increased glutamate levels, decreased the levels of other amino acids, including
      glutamine, aspartate, leucine and isoleucine, and impaired mitochondrial
      tricarboxylic acid cycle. TDP-43 induced lactate accumulation and altered the
      balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters.
      Parkin restored amino acid levels, neurotransmitter balance and tricarboxylic
      acid cycle metabolism, rescuing neurons from TDP-43-induced apoptotic death.
      Furthermore, TDP-43 expression led to an increase in 4E-BP levels, perhaps
      altering translational control and deregulating amino acid synthesis; while
      Parkin reversed the effects of TDP-43 on the 4E-BP signaling pathway. Taken
      together, these data suggest that Parkin may affect TDP-43 localization and
      mitigate its effects on 4E-BP signaling and loss of amino acid homeostasis.

PMID- 24298992
TI  - Double-patch repair by a bilateral ventriculotomy for postinfarction ventricular
      septal defect.
AB  - OBJECTIVES: Repair of a postinfarction ventricular septal defect (VSD) is a
      challenging procedure with a high risk of postoperative residual shunt and
      subsequent mortality. This retrospective study aimed to assess a modified infarct
      exclusion technique with a biventricular approach. METHODS: Nineteen consecutive
      patients who underwent the infarct exclusion procedure for VSD between 2002 and
      2011 were reviewed. A biventricular approach (B group: 6 patients) and a left
      ventricular approach (L group: 13 patients) were studied by univariate analysis.
      RESULTS: The overall 30-day mortality was 15.8%, and was not different between
      the two groups (p=0.94). Postoperative residual shunt was not observed in the B
      group (p=0.21). The overall five-year survival rate was 79%, and there were no
      late deaths in the B group (p=0.14). CONCLUSION: The repair of postinfarction VSD
      can be safely performed by the infarct exclusion technique with a biventricular
      approach. This technique seems to reduce surgical mortality and prevents
      recurrence of the VSD.

PMID- 24298993
TI  - Maternal cardiovascular profiling in the first trimester of pregnancies
      complicated with gestation-induced hypertension or fetal growth retardation: a
      pilot study.
AB  - OBJECTIVE: In this study, we determine whether maternal cardiovascular (CV)
      profiling can detect first trimester differences between women with uncomplicated
      pregnancies (UP) and those who will develop gestational hypertensive disorders
      (GHD) or normotensive fetal growth retardation (FGR). METHODS: Cardiac, arterial,
      and venous function were evaluated in 242 pregnant women around 12 weeks of
      gestation, using impedance cardiography (ICG) and combined electrocardiogram -
      Doppler ultrasonography. After postnatal determination of gestational outcome,
      first trimester measurements were compared between groups using Mann-Whitney U
      test for continuous data or Fisher's Exact test for categorical variables (SPSS
      20.0). RESULTS: Compared to UP, first trimester aortic flow velocity index [71 +/
      0.96 versus 61 +/- 4.91 1/1000/s (p = 0.016)], acceleration index [133 +/- 2.25
      versus 106 +/- 11.26 1/100/s(2) (p = 0.023)] and Heather index [23.1 +/- 0.35
      versus 19.2 +/- 1.70 Omega/s(2) (p = 0.019)] were lower in GHD pregnancies, and
      first trimester stroke volume [77 +/- 1.16 versus 67 +/- 3.97 ml (p = 0.033)] and
      cardiac output [7.3 +/- 0.10 versus 6.2 +/- 0.31 l/min (p = 0.025)] were lower in
      FGR pregnancies. CONCLUSIONS: Maternal CV function in the first trimester of
      pregnancy differs between UP and those destined to develop GHD or FGR. This can
      be assessed with non-invasive maternal CV profiling, opening perspectives for the
      application of this technique in early gestational screening for GHD and FGR.

PMID- 24298996
TI  - Flexible miniaturized nickel oxide thermistor arrays via inkjet printing
      technology.
AB  - In this study, an inkjet printing process was developed to produce thermistor
      arrays for temperature sensing applications. First, a formulation process was
      carefully performed to generate a stable nanoparticle ink for nickel oxide, a
      material with a large temperature coefficient of resistance. The thermistor was
      then fabricated by printing a square NiO thin film in between two parallel silver
      conductive tracks on either glass plates or polyimide films. The printed
      thermistor, which has an adjustable dimension with a sub-millimeter scale, can
      operate over a wide range from room temperature to 200  degrees C with great
      sensitivity (B values ~4300 K) without hysteretic effects. When printed on
      polyimide films, the thermistors can also be bent or attached to curved surfaces
      to provide accurate and reliable temperature measurements. Moreover, the
      thermistor responds quickly to small temperature changes and provides an
      effective tool for transient temperature measurements. Finally, a thermistor
      array was fabricated to show the flexibility of this inkjet printing process and
      to demonstrate the applicability of the printed devices for temperature sensing
      applications.

PMID- 24298994
TI  - Generation of a human airway epithelium derived basal cell line with multipotent
      differentiation capacity.
AB  - BACKGROUND: As the multipotent progenitor population of the airway epithelium,
      human airway basal cells (BC) replenish the specialized differentiated cell
      populations of the mucociliated airway epithelium during physiological turnover
      and repair. Cultured primary BC divide a limited number of times before entering
      a state of replicative senescence, preventing the establishment of long-term
      replicating cultures of airway BC that maintain their original phenotype.
      METHODS: To generate an immortalized human airway BC cell line, primary human
      airway BC obtained by brushing the airway epithelium of healthy nonsmokers were
      infected with a retrovirus expressing human telomerase (hTERT). The resulting
      immortalized cell line was then characterized under non-differentiating and
      differentiating air-liquid interface (ALI) culture conditions using ELISA, TaqMan
      quantitative PCR, Western analysis, and immunofluorescent and immunohistochemical
      staining analysis for cell type specific markers. In addition, the ability of the
      cell line to respond to environmental stimuli under differentiating ALI culture
      was assessed. RESULTS: We successfully generated an immortalized human airway BC
      cell line termed BCi-NS1 via expression of hTERT. A single cell derived clone
      from the parental BCi-NS1 cells, BCi-NS1.1, retains characteristics of the
      original primary cells for over 40 passages and demonstrates a multipotent
      differentiation capacity into secretory (MUC5AC, MUC5B), goblet (TFF3), Clara
      (CC10) and ciliated (DNAI1, FOXJ1) cells on ALI culture. The cells can respond to
      external stimuli such as IL-13, resulting in alteration of the normal
      differentiation process. CONCLUSION: Development of immortalized human airway BC
      that retain multipotent differentiation capacity over long-term culture should be
      useful in understanding the biology of BC, the response of BC to environmental
      stress, and as a target for assessment of pharmacologic agents.

PMID- 24298995
TI  - Comparison of insulin lispro protamine suspension versus insulin glargine once
      daily added to oral antihyperglycaemic medications and exenatide in type 2
      diabetes: a prospective randomized open-label trial.
AB  - AIMS: To compare efficacy and safety of two, once-daily basal insulin
      formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine
      (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID
      in suboptimally controlled type 2 diabetes (T2D) patients. METHODS: This 24-week,
      open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or
      glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by
      comparing the upper limit of 95% confidence intervals (CIs) for change in
      haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c)
      with non-inferiority margin 0.4%. RESULTS: Non-inferiority of ILPS versus
      glargine was demonstrated: least-squares mean between-treatment difference (ILPS
      minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less
      for ILPS- versus glargine-treated patients (-1.16 +/- 0.84 vs. -1.40 +/- 0.97%, p
      = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine)
      (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence
      (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients
      treated with ILPS versus glargine (p = 0.004). Weight gain was similar between
      groups (ILPS: 0.27 +/- 3.38 kg; glargine: 0.66 +/- 3.93 kg, p = NS). Endpoint
      total insulin doses were lower in patients treated with ILPS versus glargine
      (0.30 +/- 0.17 vs. 0.37 +/- 0.17 IU/kg/day, p < 0.001). CONCLUSIONS: ILPS was non
      inferior to glargine for HbA1c change over 24 weeks, but was associated with less
      HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin
      therapy improves glycaemic control and is associated with minimal weight gain
      when added to OAMs and exenatide BID for suboptimally controlled T2D.

PMID- 24298997
TI  - SKB1/PRMT5-mediated histone H4R3 dimethylation of Ib subgroup bHLH genes
      negatively regulates iron homeostasis in Arabidopsis thaliana.
AB  - Histone modifications play critical roles in the perception of environmental cues
      by plants. Here, we report that Shk1 binding protein 1 (SKB1/AtPRMT5), which
      catalyzes the symmetric dimethylation of histone H4R3 (H4R3sme2), is involved in
      iron homeostasis in Arabidopsis. The SKB1 lesion mutant exhibited higher iron
      accumulation in shoots and greater tolerance to iron deficiency than the wild
      type. The expression of SKB1 was not affected by iron, but the level of H4R3sme2
      mediated by SKB1 was related to iron status in plants. We showed by chromatin
      immunoprecipitation (ChIP) and genome-wide ChIP-seq that SKB1 associated with the
      chromatin of the Ib subgroup bHLH genes (AtbHLH38, AtbHLH39, AtbHLH100 and
      AtbHLH101), and symmetrically dimethylated histone H4R3. The quantity of SKB1
      that associated with chromatin of the Ib subgroup bHLH genes and the level of
      H4R3sme2 corresponded to the iron status of plants (higher with increased iron
      supply and lower when iron was removed). We conclude that SKB1-mediated H4R3sme2
      regulates iron homeostasis in Arabidopsis in the context of increasing or
      decreasing expression of Ib subgroup bHLH genes. Iron deficiency may cause an
      increase in the disassociation of SKB1 from chromatin of the bHLH genes and a
      decrease in the level of H4R3sme2, thereby elevating their transcription and
      enhancing iron uptake. Our findings provide new insight into the molecular
      mechanisms of iron homeostasis in strategy I plants. 

PMID- 24298999
TI  - Polybrominated diphenyl ethers, polychlorinated biphenyls, and persistent
      pesticides in serum from the national health and nutrition examination survey:
      2003-2008.
AB  - Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and
      persistent pesticides have been measured in pooled samples representative of the
      general noninstitutionalized population of the United States. The pools were made
      from individual sera from the National Health and Nutrition Examination Survey
      (NHANES) during 2005/06 and 2007/08. The pooled concentrations have been
      contrasted to NHANES 2003/04 individual measurements to evaluate changes in
      concentration over time and within survey period differences among age groups,
      race/ethnicity groups (Mexican American, non-Hispanic Black, non-Hispanic White),
      and sex. The arithmetic mean serum concentrations of several PCB congeners
      decreased from NHANES 2003/04 through 2007/08. Larger percentage reductions were
      seen for younger subjects (12-19 years) compared with older subjects (>=60
      years). For example, the arithmetic mean concentration of 2,2',4,4',5,5'
      hexachlorobiphenyl (PCB-153) was 36% lower in 12-19 year old adolescents when
      comparing NHANES 2007/08 with 2003/04; while for subjects over the age of 60 a
      14% lower concentration was seen, although, the 95% confidence intervals
      overlapped. Similarly, the arithmetic mean serum concentrations of tri- to
      hexaBDEs were lower in NHANES 2007/08 than in 2003/04; however, most confidence
      intervals of the arithmetic means overlapped. These findings suggest that a
      reduction in PBDE serum concentrations cannot yet be detected following the
      discontinuation of pentaBDE in 2004. 

PMID- 24298998
TI  - Changes in DXA and quantitative CT measures of musculoskeletal outcomes following
      pediatric renal transplantation.
AB  - This prospective study evaluated changes in dual energy X-ray absorptiometry
      (DXA) whole body bone mineral content (WB-BMC) and spine areal bone mineral
      density (spine-BMD), and tibia quantitative computed tomography (QCT) trabecular
      and cortical volumetric BMD and cortical area in 56 children over 12 months
      following renal transplantation. At transplant, spine-BMD Z-scores were greater
      in younger recipients (<13 years), versus 898 reference participants (p < 0.001).
      In multivariate models, greater decreases in spine-BMD Z-scores were associated
      with greater glucocorticoid dose (p < 0.001) and declines in parathyroid hormone
      levels (p = 0.008). Changes in DXA spine-BMD and QCT trabecular BMD were
      correlated (r = 0.47, p < 0.01). At 12 months, spine-BMD Z-scores remained
      elevated in younger recipients, but did not differ in older recipients (>= 13)
      and reference participants. Baseline WB-BMC Z-scores were significantly lower
      than reference participants (p = 0.02). Greater glucocorticoid doses were
      associated with declines in WB-BMC Z-scores (p < 0.001) while greater linear
      growth was associated with gains in WB-BMC Z-scores (p = 0.01). Changes in WB-BMC
      Z-scores were associated with changes in tibia cortical area Z-scores (r = 0.52,
      p < 0.001), but not changes in cortical BMD Z-scores. Despite resolution of
      muscle deficits, WB-BMC Z-scores at 12 months remained significantly reduced.
      These data suggest that spine and WB DXA provides insight into trabecular and
      cortical outcomes following pediatric renal transplantation.

PMID- 24299000
TI  - Evaluation of endocrine function in children admitted to pediatric intensive care
      unit.
AB  - BACKGROUND: Although studied widely in adulthood, little is known about
      endocrinological disorders during critical illnesses in childhood. The aims of
      this study were to define the endocrinological changes in patients admitted to
      pediatric intensive care unit (PICU) and to identify their effects on prognosis.
      METHODS: Forty patients with a mean age of 5.1 years admitted to PICU were
      enrolled in the study. Blood samples were taken at admission and at 24 and 48 h
      to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth
      hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding
      protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient's
      condition was assessed using pediatric risk of mortality (PRISM) and pediatric
      logistic organ dysfunction (PELOD) scores. RESULTS: PRISM and PELOD scores were
      significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP
      3 and IL-6 were not significantly different between the survivors and non
      survivors. There was a negative correlation between baseline IGFBP-3 and PRISM
      scores. A positive correlation was seen between cortisol level at 24 h and PRISM
      score. On multivariate linear regression analysis, PRISM score was best explained
      by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL
      6 at 24 h and PELOD scores. CONCLUSIONS: Although there was no difference between
      survivors and non-survivors regarding the studied endocrine parameters, there
      were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment
      scores, and, given that these scores correlated with mortality, these parameters
      might be useful as prognostic factors.

PMID- 24299001
TI  - Proportion of adults achieving sufficient physical activity increases in South
      Australia, 1998 - 2010.
AB  - BACKGROUND: The South Australian Department of Health has administered the Active
      Australia Survey triennially since 1998 to assess physical activity levels in the
      South Australian adult population. Survey findings may reflect the impact of
      health messages on the population and provide evidence to inform public health
      policy.This study analyzed the data from the South Australian Active Australia
      Surveys from 1998 to 2010 to quantify trends in the physical activity patterns of
      the total population and groups within the population over this period. METHODS:
      The study used a retrospective analysis of the SA Health Active Australia Surveys
      of 1998, 2001, 2004, 2007, and 2010. Data were age-adjusted to the Australian
      2001 Population Census. Proportions reporting sufficient physical activity for
      health benefits (>= 150 min/week) were calculated by year of survey, and
      according to the following variables: gender, age group, area, educational level,
      income bracket, and body mass index (BMI). Population proportions statistics were
      used to determine the significance of the changes in levels of physical activity
      between 1998 and 2010. RESULTS: The main finding was a significant increase in
      the overall proportion of the population reporting sufficient physical activity.
      However, the changes were not uniform across categories. Differences in
      proportions reporting sufficient physical activity appear to have narrowed within
      the categories of gender and BMI but have widened within the categories of
      educational level and income bracket. Changes were relatively consistent across
      age and geographic location. CONCLUSIONS: The results suggest that government
      programs to increase engagement in regular physical activity have been effective
      in some groups within the total population. They provide strong evidence to
      support the need for better ways of increasing physical activity levels and thus
      improving health outcomes for disadvantaged groups in the South Australian
      population.

PMID- 24299002
TI  - Dynamics of Galphaq-protein-p63RhoGEF interaction and its regulation by RGS2.
AB  - Some G-protein-coupled receptors regulate biological processes via Galpha12/13-
      or Galphaq/11-mediated stimulation of RhoGEFs (guanine-nucleotide-exchange
      factors). p63RhoGEF is known to be specifically activated by Galphaq/11 and
      mediates a major part of the acute response of vascular smooth muscle cells to
      angiotensin II treatment. In order to gain information about the dynamics of
      receptor-mediated activation of p63RhoGEF, we developed a FRET-based assay to
      study interactions between Galphaq-CFP and Venus-p63RhoGEF in single living
      cells. Upon activation of histaminergic H1 or muscarinic M3 receptors, a robust
      FRET signal occurred that allowed for the first time the analysis of the kinetics
      of this interaction in detail. On- and off-set kinetics of Galphaq-p63RhoGEF
      interactions closely resembled the kinetics of Galphaq activity. Analysis of the
      effect of RGS2 (regulator of G-protein signalling 2) on the dynamics of Galphaq
      activity and their interaction with p63RhoGEF showed that RGS2 is able to
      accelerate both deactivation of Galphaq proteins and dissociation of Galphaq and
      p63RhoGEF to a similar extent. Furthermore, we were able to detect activation
      dependent FRET between RGS2 and p63RhoGEF and observed a reduced p63RhoGEF
      mediated downstream signalling in the presence of RGS2. In summary, these
      observations support the concept of a functional activation-dependent p63RhoGEF
      Galphaq-RGS2 complex. 

PMID- 24299003
TI  - Activation of soluble guanylyl cyclase prevents foam cell formation and
      atherosclerosis.
AB  - AIMS: Soluble guanylyl cyclase (sGC) is a key modulator in the regulation of
      vascular tone. However, its role and involving mechanism in cholesterol
      metabolism of macrophages and atherosclerosis remain unclear. METHODS: Oil red O
      staining, Dil-oxidized low-density lipoprotein (oxLDL)-binding assay and
      cholesterol efflux assay were performed in biology of foam cells. Levels of
      cytokines or intracellular lipid were evaluated by ELISA or colorimetric kits.
      Expression of gene or protein was determined by quantitative real-time PCR or
      Western blotting. Histopathology was examined by haematoxylin and eosin staining.
      RESULTS: Soluble guanylyl cyclase was expressed in macrophages of mouse
      atherosclerotic lesions. Treatment with 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ, sGC inhibitor) exacerbated oxLDL-induced cholesterol accumulation in
      macrophages. In contrast, 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1,
      sGC activator) attenuated the oxLDL-induced cholesterol accumulation because of
      increased cholesterol efflux. Additionally, YC-1 dose dependently increased the
      protein expression of ATP-binding cassette transporter A1 (ABCA1) but did not
      alter that of scavenger receptor class A (SR-A), CD36, SR-BI or ABCG1. Moreover,
      YC-1-upregulated ABCA1 level depended on liver X receptor alpha (LXRalpha).
      Inhibition of the LXRalpha-ABCA1 pathway by LXRalpha small interfering RNA
      (siRNA), ABCA1 neutralizing antibody or ABCA1 siRNA abolished the effect of YC-1
      on cholesterol accumulation and cholesterol efflux. In vivo, YC-1 retarded the
      development of atherosclerosis, accompanied by reduced serum levels of
      cholesterol and pro-inflammatory cytokines, in apolipoprotein E-deficient mice.
      CONCLUSION: Activation of sGC by YC-1 leads to LXRalpha-dependent upregulation of
      ABCA1 in macrophages and may confer protection against atherosclerosis.

PMID- 24299004
TI  - Functional characterization of the mutations in Pepper mild mottle virus
      overcoming tomato tm-1-mediated resistance.
AB  - In tomato plants, Pepper mild mottle virus (PMMoV) cannot replicate because the
      tm-1 protein inhibits RNA replication. The resistance of tomato plants to PMMoV
      remains durable both in the field and under laboratory conditions. In this study,
      we constructed several mutant PMMoVs and analysed their abilities to replicate in
      tomato protoplasts and plants. We found that two mutants, PMMoV-899R,F976Y and
      PMMoV-899R,F976Y,D1098N, were able to replicate in tomato protoplasts, but only
      PMMoV-899R,F976Y,D1098N was able to multiply in tomato plants. Further analysis
      showed that the D1098N mutation of the replication proteins weakened the
      inhibitory effect of the tm-1 protein and enhanced the replication efficiency of
      PMMoV-899R,F976Y,D1098N. We also observed that the infectivity of the viruses
      decreased in the order wild-type PMMoV > PMMoV-899R,F976Y > PMMoV
      899R,F976Y,D1098N in original host plants, pepper and tobacco plants. On the
      contrary, the single mutation D1098N abolished PMMoV replication in tobacco
      protoplasts. On the basis of these observations, it is likely that the
      deleterious side-effects of mutations in replication proteins prevent the
      emergence of PMMoV mutants that can overcome tm-1-mediated resistance. 

PMID- 24299005
TI  - Food safety and hygiene lessons in the primary school: implications for risk
      reduction behaviors.
AB  - OBJECTIVE: This study describes an effective educational program to improve
      children's knowledge about characteristics of microorganisms and food
      contamination, and their personal hygiene behaviors. MATERIALS AND METHODS:
      Between November 2011 and March 2012, a health campaign, targeted at fifth-grade
      students of 12 public primary compulsory schools, was conceived. Participants
      were divided into two classes, a theoretical class and a practical class based on
      two different teaching approaches. To address children's knowledge and behaviors
      on the program topics and to monitor the effectiveness of the health campaign on
      changing pre-existent concepts and habits, pre- and post-intervention
      questionnaires were administered both to students and parents. Poisson and
      binomial mixed models were performed. RESULTS: Two hundred forty-nine children
      were enrolled. Results show an overall improvement in children's knowledge both
      for the practical and theoretical classes (incident risk ratios [IRRs]: 1.2, 95%
      confidence interval (CI) 1.1-1.2, p<0.001 and 1.1, 95% CI 1.0-1.1, p<0.001, post-
      versus pre-intervention). The same effect was observed for children's behavior,
      comparing post- versus pre-intervention for both groups (IRRs were 3.4, 95% CI
      2.2-5.2, p<0.001 and 3.2 95% CI 1.9-5.5, p<0.001). CONCLUSION AND APPLICATIONS:
      The methodology described in this article might be usefully adopted to conduct
      food safety classes, contributing to the amelioration of children's awareness on
      food related risks and leading to significant benefit for primary prevention.

PMID- 24299006
TI  - Randomized control trial comparing calcium hydroxide and mineral trioxide
      aggregate for partial pulpotomies in cariously exposed pulps of permanent molars.
AB  - AIM: To compare the treatment outcomes when calcium hydroxide and mineral
      trioxide aggregate are used for partial pulpotomy in cariously exposed young
      permanent molars in a randomized control trial. METHODOLOGY: Eighty-four teeth in
      80 volunteers (aged 7-10 years) with reversible pulpitis and carious pulp
      exposures were randomly divided into two groups. Exposed pulps were severed using
      high-speed round burs until fresh pulp was seen. Cavities were irrigated with
      2.5% sodium hypochlorite, and the pulp exposures were photographed and measured.
      Dycal or ProRoot MTA was placed on the pulp. Vitremer was placed over the
      material until the remaining cavity was 2 mm deep; amalgam was then placed. Teeth
      were evaluated for clinical symptoms and radiographic periapical changes after 24
      h, 3 months, 6 months, 1 year and 2 years. Mean survival times and incidence of
      extraction were calculated using exact binomial confidence intervals. RESULTS:
      The median survival time for both ProRoot MTA and Dycal groups was 24 months.
      Three teeth had unfavourable outcomes with the incidence rate of 0.20/100 tooth
      months with ProRoot MTA (95% CI: 0.02-0.71) and 0.11/100 tooth-months with Dycal
      (95% CI: 0.001-0.60). The incidence of unfavourable outcomes was 0.05/100 (95%
      CI: 0.001-0.30) and 2.38/100 (95% CI: 0.29-8.34) tooth-months in teeth with small
      (<5 mm(2) ) and large (>5 mm(2) ) pulp exposure areas, respectively. CONCLUSIONS:
      Partial pulpotomy in teeth of young patients with reversible pulpitis, either
      using ProRoot MTA or Dycal, resulted in favourable treatment outcomes for up to 2
      years. The incidence of unfavourable outcomes tended to be higher in teeth with
      pulp exposure areas larger than 5 mm(2) .

PMID- 24299007
TI  - Cone beam computed tomography evaluation of regenerated buccal bone 5 years after
      simultaneous implant placement and guided bone regeneration procedures--a
      randomized, controlled clinical trial.
AB  - PURPOSE: The aim of this controlled clinical study was to compare a polyethylene
      glycol membrane (PEG) used for bone regeneration of peri-implant defects to a
      collagen membrane with respect to implant survival rate, dimensions of buccal
      peri-implant bone and mucosa. MATERIALS AND METHODS: Thirty-seven patients who
      received single tooth implants with simultaneous guided bone regeneration (GBR)
      in the posterior maxilla or mandible were enrolled in the study. Intra-operative
      heights of bone defects were assessed prior to bone augmentation. The defects
      were augmented with xenogenic bone mineral and randomly covered either with a
      porcine collagen membrane (control) or with a PEG membrane (test). Five years
      after implant placement, clinical evaluation and cone beam computed tomography
      (CBCT) scans were performed. Remaining height of bone defect, horizontal bone
      thickness, level of mucosal margin, and mucosal thickness were assessed in CBCT
      images. The difference of height of bone defect at implant placement and at 5
      year follow-up was calculated. The differences between the two groups were
      analyzed using two-sided t-test and Mann-Whitney U-test. RESULTS: After 5 years,
      32 patients could be included and exhibited an implant survival rate of 100% for
      both groups. The buccal vertical bone gain between implant placement and 5-year
      follow-up amounted at 4.3 +/- 1.5 (SD) mm and 4.8 +/- 2.6 (SD) mm for the control
      and the test group, respectively (P = 0.493). Neither the bone height nor the
      thickness reached statistical significant differences between the two groups. The
      distance between mucosal margin and implant shoulder resulted in 0.8 +/- 0.7 (SD)
      mm in the control and 0.5 +/- 0.8 (SD) mm in the test group (P = 0.198). The
      mucosal thickness reached 1.4 +/- 0.5 (SD) mm in the control and 1.3 +/- 0.3 (SD)
      mm in the test group (P = 0.715). There were no significant correlations between
      height of bone defect at baseline and at follow-up examination and between
      different 5-year parameters. CONCLUSION: A polyethylene glycol membrane used for
      bone regeneration of peri-implant defects performed as successfully as a collagen
      membrane with respect to implant survival rate and dimensions of the buccal peri
      implant bone and mucosa after 5 years.

PMID- 24299009
TI  - Coronary flow reserve predicts cardiopulmonary fitness in patients with coronary
      artery disease independently of systolic and diastolic function.
AB  - AIMS: Despite revascularization and optimal medical treatment, patients with
      coronary artery disease (CAD) have reduced exercise capacity. In the absence of
      coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary
      microvascular function, and a marker of future poor outcome in CAD patients. The
      aim of this study was to examine the relationship among CFR, systolic and
      diastolic function, peripheral vascular function, and cardiopulmonary fitness in
      CAD patients. METHODS AND RESULTS: Forty patients with median left ventricular
      ejection fraction (LVEF) 49 (interquartile 46-55) with documented CAD without
      significant left anterior descending artery (LAD) stenosis underwent
      cardiorespiratory exercise test with measurement of VO2 peak, digital measurement
      of endothelial function and arterial stiffness, and an echocardiography with
      measurement of LVEF using the biplane Simpson model, mitral early (E) and late
      (A) inflow velocities, and tissue Doppler diastolic (e') and systolic (s')
      velocities. Peak coronary flow velocity (CFV) was measured in the LAD using pulse
      wave Doppler. CFR was calculated as the ratio between peak CFV at rest and during
      vasodilator stress. Median CFR was 2.22 (1.90-2.62) and VO2 peak was 21.8 (17.6
      25.5). VO2 peak correlated significantly with CFR (r = 0.57, P < 0.001), E/e' (r
      = -0.35, P = 0.04), and s' (r = 0.41, P = 0.01) and with LVEF (r = 0.35, P =
      0.03). CFR remained independently associated with VO2 peak after adjustment for
      systolic and diastolic function. CONCLUSIONS: Coronary flow reserve measured
      noninvasively predicts cardiopulmonary fitness independently of resting systolic
      and diastolic function in CAD patients, indicating that cardiac output during
      maximal exercise is dependent on the ability of the coronary circulation to adapt
      to the higher metabolic demands of the myocardium.

PMID- 24299010
TI  - A streptavidin-SOG chimera for all-optical immunoassays.
AB  - Immunological detection has been developed into a sensitive and versatile
      technique and is based on two requisite elements: targeting antibodies and an
      indicator, usually in the form of horseradish peroxidase or alkaline phosphatase.
      The specificity and turnover rate of these enzymes provide an efficient means of
      signal amplification, but both require a stopping agent to prevent
      overdevelopment, which limits scalability to mechanized fluidic systems. As an
      alternative, we present a fully optical detection system based on a streptavidin
      singlet oxygen generating chimeric protein that produces singlet oxygen from blue
      light. When used with trans-1-(2'-methoxyvinyl)pyrene, the photosynthetic
      streptavidin combines indicator development and reporting in sufficiently
      distinct visible wavelengths while retaining the sensitivity and scale of
      enzymatic systems that use horseradish peroxidase. By combining photosensitive
      development and detection into one system, we can enable future, highly parallel
      immunological testing to be controlled with the spatial and temporal precision of
      light. 

PMID- 24299011
TI  - Dendrimers - from organic synthesis to pharmaceutical applications: an update.
AB  - Dendrimers are a relatively new class of monodisperse polymers, which have tree
      like spherical structures with well-defined sizes and shapes. Their unique
      structure has a significant impact on their physical and chemical properties.
      Research on dendrimers is of significant interest to scientists from all areas
      and their utility in various scientific fields, including pharmaceuticals, is
      expanding. The present review is comprehensive and covers different aspects of
      dendrimers viz. (1) synthesis, (2) properties and (3) pharmaceutical
      applications. The emphasis is on their applications as well as the current
      ongoing research status for drug targeting.

PMID- 24299012
TI  - Wide wavelength tuning of optical antennas on graphene with nanosecond response
      time.
AB  - Graphene is emerging as a broadband optical material which can be dynamically
      tuned by electrostatic doping. However, the direct application of graphene sheets
      in optoelectronic devices is challenging due to graphene's small thickness and
      the resultant weak interaction with light. By combining metal and graphene in a
      hybrid plasmonic structure, it is possible to enhance graphene-light interaction
      and thus achieve in situ control of the optical response. We show that the
      effective mode index of the bonding plasmonic mode in metal-insulator-metal (MIM)
      waveguides is particularly sensitive to the change in the optical conductivity of
      a graphene layer in the gap. By incorporating such MIM structures in optic
      antenna designs, we demonstrate an electrically tunable coupled antenna array on
      graphene with a large tuning range (1100 nm, i.e., 250 cm(-1), nearly 20% of the
      resonance frequency) of the antenna resonance wavelength at the mid-infrared
      (MIR) region. Our device exhibits a 3 dB cutoff frequency of 30 MHz, which can be
      further increased into the gigahertz range. This study confirms that hybrid metal
      graphene structures are promising elements for high-speed electrically
      controllable optical and optoelectronic devices. 

PMID- 24299014
TI  - BF3.etherate-mediated Friedel-Crafts arylation of 2-hydroxy-1,4-benzoxazines:
      synthesis of 2-aryl-1,4-benzoxazine derivatives.
AB  - BF3.etherate-mediated carbon-carbon bond formation by the Friedel-Crafts
      arylation of 2-hydroxybenzoxazine derivatives with various electron-rich arenes
      is reported. The current protocol provides an easy access for the synthesis of a
      series of densely substituted 2-aryl-1,4-benzoxazine derivatives under mild
      conditions. 

PMID- 24299013
TI  - Field-SEA: a model for computing the solvation free energies of nonpolar, polar,
      and charged solutes in water.
AB  - Previous work describes a computational solvation model called semi-explicit
      assembly (SEA). The SEA water model computes the free energies of solvation of
      nonpolar and polar solutes in water with good efficiency and accuracy. However,
      SEA gives systematic errors in the solvation free energies of ions and charged
      solutes. Here, we describe field-SEA, an improved treatment that gives accurate
      solvation free energies of charged solutes, including monatomic and polyatomic
      ions and model dipeptides, as well as nonpolar and polar molecules. Field-SEA is
      computationally inexpensive for a given solute because explicit-solvent model
      simulations are relegated to a precomputation step and because it represents
      solvating waters in terms of a solute's free-energy field. In essence, field-SEA
      approximates the physics of explicit-model simulations within a computationally
      efficient framework. A key finding is that an atom's solvation shell inherits
      characteristics of a neighboring atom, especially strongly charged neighbors.
      Field-SEA may be useful where there is a need for solvation free-energy
      computations that are faster than explicit-solvent simulations and more accurate
      than traditional implicit-solvent simulations for a wide range of solutes. 

PMID- 24299015
TI  - A novel method to synthesize highly photoactive Cu2O microcrystalline films for
      use in photoelectrochemical cells.
AB  - Large-scale and high-quality Cu2O microcrystalline films with high photoactivity
      are synthesized using a novel and low-cost method. The enhanced photoactivity is
      achieved through the formation of Cu2O microcrystalline films having well-defined
      crystal facets and porous structure. Cu2O microcrystalline films are fabricated
      by decomposing previously synthesized Cu(OH)2 nanowires on a Cu foil under a
      vacuum. Subsequent crystal growth during the annealing process is driven by
      outward diffusion of Cu ions and oxidation. Crystal growth induces coalescence of
      the nanowires and results in the formation of Cu2O microcrystals enclosed by four
      {111} facets. Photoelectrochemical evaluation of the annealed samples performed
      under chopped simulated AM 1.5G illumination reveals that the sample annealed at
      500  degrees C for 2 h exhibited the highest photocurrent of 4.07 mA/cm(2) at 0
      V/RHE. This large photocurrent is ascribed to a high carrier density (~1.36 *
      10(18) cm(-3)) and a low carrier transfer resistance in electrolyte, as evidenced
      by electrochemical impedance spectroscopy. The obtained low-cost Cu2O
      microcrystalline film (2 h) may serve as an excellent solar absorber and carrier
      provider for use in photovoltaics and artificial photosynthesis.

PMID- 24299016
TI  - Profiling risk factors for chronic uveitis in juvenile idiopathic arthritis: a
      new model for EHR-based research.
AB  - BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in
      children. Chronic uveitis is a common and serious comorbid condition of juvenile
      idiopathic arthritis, with insidious presentation and potential to cause
      blindness. Knowledge of clinical associations will improve risk stratification.
      Based on clinical observation, we hypothesized that allergic conditions are
      associated with chronic uveitis in juvenile idiopathic arthritis patients.
      METHODS: This study is a retrospective cohort study using Stanford's clinical
      data warehouse containing data from Lucile Packard Children's Hospital from 2000
      2011 to analyze patient characteristics associated with chronic uveitis in a
      large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16
      years of age were processed via a validated text analytics pipeline. Bivariate
      associated variables were used in a multivariate logistic regression adjusted for
      age, gender, and race. Previously reported associations were evaluated to
      validate our methods. The main outcome measure was presence of terms indicating
      allergy or allergy medications use overrepresented in juvenile idiopathic
      arthritis patients with chronic uveitis. Residual text features were then used in
      unsupervised hierarchical clustering to compare clinical text similarity between
      patients with and without uveitis. RESULTS: Previously reported associations with
      uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis
      diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of
      psoriasis) were reproduced in our study. Use of allergy medications and terms
      describing allergic conditions were independently associated with chronic
      uveitis. The association with allergy drugs when adjusted for known associations
      remained significant (OR 2.54, 95% CI 1.22-5.4). CONCLUSIONS: This study shows
      the potential of using a validated text analytics pipeline on clinical data
      warehouses to examine practice-based evidence for evaluating hypotheses formed
      during patient care. Our study reproduces four known associations with uveitis
      development in juvenile idiopathic arthritis patients, and reports a new
      association between allergic conditions and chronic uveitis in juvenile
      idiopathic arthritis patients.

PMID- 24299017
TI  - Heterodimeric protein complex identification by naive Bayes classifiers.
AB  - BACKGROUND: Protein complexes are basic cellular entities that carry out the
      functions of their components. It can be found that in databases of protein
      complexes of yeast like CYC2008, the major type of known protein complexes is
      heterodimeric complexes. Although a number of methods for trying to predict sets
      of proteins that form arbitrary types of protein complexes simultaneously have
      been proposed, it can be found that they often fail to predict heterodimeric
      complexes. RESULTS: In this paper, we have designed several features
      characterizing heterodimeric protein complexes based on genomic data sets, and
      proposed a supervised-learning method for the prediction of heterodimeric protein
      complexes. This method learns the parameters of the features, which are embedded
      in the naive Bayes classifier. The log-likelihood ratio derived from the naive
      Bayes classifier with the parameter values obtained by maximum likelihood
      estimation gives the score of a given pair of proteins to predict whether the
      pair is a heterodimeric complex or not. A five-fold cross-validation shows good
      performance on yeast. The trained classifiers also show higher predictability
      than various existing algorithms on yeast data sets with approximate and exact
      matching criteria. CONCLUSIONS: Heterodimeric protein complex prediction is a
      rather harder problem than heteromeric protein complex prediction because
      heterodimeric protein complex is topologically simpler. However, it turns out
      that by designing features specialized for heterodimeric protein complexes,
      predictability of them can be improved. Thus, the design of more sophisticate
      features for heterodimeric protein complexes as well as the accumulation of more
      accurate and useful genome-wide data sets will lead to higher predictability of
      heterodimeric protein complexes. Our tool can be downloaded from
      http://imi.kyushu-u.ac.jp/~om/.

PMID- 24299018
TI  - Distinct Pseudomonas type-III effectors use a cleavable transit peptide to target
      chloroplasts.
AB  - The pathogen Pseudomonas syringae requires a type-III protein secretion system
      and the effector proteins it injects into plant cells for pathogenesis. The
      primary role for P. syringae type-III effectors is the suppression of plant
      immunity. The P. syringae pv. tomato DC3000 HopK1 type-III effector was known to
      suppress the hypersensitive response (HR), a programmed cell death response
      associated with effector-triggered immunity. Here we show that DC3000 hopK1
      mutants are reduced in their ability to grow in Arabidopsis, and produce reduced
      disease symptoms. Arabidopsis transgenically expressing HopK1 are reduced in PAMP
      triggered immune responses compared with wild-type plants. An N-terminal region
      of HopK1 shares similarity with the corresponding region in the well-studied type
      III effector AvrRps4; however, their C-terminal regions are dissimilar,
      indicating that they have different effector activities. HopK1 is processed in
      planta at the same processing site found in AvrRps4. The processed forms of HopK1
      and AvrRps4 are chloroplast localized, indicating that the shared N-terminal
      regions of these type-III effectors represent a chloroplast transit peptide. The
      HopK1 contribution to virulence and the ability of HopK1 and AvrRps4 to suppress
      immunity required their respective transit peptides, but the AvrRps4-induced HR
      did not. Our results suggest that a primary virulence target of these type-III
      effectors resides in chloroplasts, and that the recognition of AvrRps4 by the
      plant immune system occurs elsewhere. Moreover, our results reveal that distinct
      type-III effectors use a cleavable transit peptide to localize to chloroplasts,
      and that targets within this organelle are important for immunity. 

PMID- 24299019
TI  - Atorvastatin plus omega-3 fatty acid ethyl ester decreases very-low-density
      lipoprotein triglyceride production in insulin resistant obese men.
AB  - AIM: To test the effect of atorvastatin (ATV) and ATV plus omega-3 FAEEs on VLDL
      TG metabolism in obese, insulin resistant men. METHODS: We carried out a 6-week
      randomized, placebo-controlled study to examine the effect of ATV (40 mg/day) and
      ATV plus omega-3 FAEEs (4 g/day) on VLDL-TG metabolism in 36 insulin resistant
      obese men. VLDL-TG kinetics were determined using d5 -glycerol, gas
      chromatography-mass spectrometry and compartmental modelling. RESULTS: Compared
      with the placebo, ATV significantly decreased VLDL-TG concentration (-40%, p <
      0.001) by increasing VLDL-TG fractional catabolic rate (FCR) (+47%, p < 0.01).
      ATV plus omega-3 FAEEs lowered VLDL-TG concentration to a greater degree compared
      with placebo (-46%, p < 0.001) or ATV monotherapy (-13%, p = 0.04). This was
      achieved by a reduction in VLDL-TG production rate (PR) compared with placebo (
      32%, p = 0.008) or ATV (-20%, p = 0.03) as well as a reciprocal increase in VLDL
      TG FCR (+42%, p < 0.05) compared with placebo. CONCLUSION: In insulin resistant,
      dyslipidaemic, obese men, ATV improves VLDL-TG metabolism by increasing VLDL-TG
      FCR. The addition of 4 g/day omega-3 FAEE to statin therapy provides further TG
      lowering by lowering VLDL-TG PR.

PMID- 24299020
TI  - Personality, relationships, and health.
AB  - This special issue of the Journal of Personality focuses on the importance of
      considering both personality and relationship forces when examining physical and
      psychological health. The nine articles presented in this issue employed a
      variety of research designs, theoretical rationales, health outcomes, and
      advanced statistical methodologies in order to better understand how both
      individual differences and social factors are relevant to our health. These
      articles embody several prominent themes: Conscientiousness is a robust predictor
      of health; traits beyond the Five-Factor Model should be considered in attempts
      to understand personality, relationships, and health; links among personality,
      relationships, and health begin early in life; and relationship transitions are
      consequential to health. It is hoped that these studies inspire personality
      researchers to consider the relationship context of health and relationship
      researchers to consider individual differences when attempting to understand
      health behaviors and outcomes. 

PMID- 24299021
TI  - Add-on therapy with montelukast in the treatment of Henoch-Schonlein purpura.
AB  - BACKGROUND: Previous studies suggested that leukotrienes (LT) were involved in
      the pathogenesis of Henoch-Schonlein purpura (HSP). This study investigated the
      efficacy of an add-on therapy with montelukast in the treatment of HSP. METHODS:
      In this four-center, double-blind, placebo-controlled, parallel paired
      comparative study, 130 children with HSP were divided into two large groups: 84
      patients without nephritis and 46 patients with nephritis. For each pair of
      patients with the same severity of disease, one subject was randomly allocated to
      one subgroup and the other allocated to the other subbroup; one subgroup received
      routine treatment plus placebo treatment, while the other subgroup received
      routine treatment plus montelukast treatment for 3 months. The efficacy was
      determined using Severity Scale Score (SSS). Blood eosinophil count, eosinophil
      cationic protein (ECP), IgE, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-17, LTB4 ,
      and urinary LTE4 were measured. RESULTS: Add-on therapy with montelukast
      alleviated the symptoms of HSP including purpura, abdominal pain, stool occult
      blood, arthritis, proteinuria and hematuria, and, accordingly, shortened the
      length of hospital stay, and lowered blood eosinophil count, ECP, IgE, IL-4, IL
      5, IL-6, IL-8, IL-17, LTB4 , and urinary LTE4 production, and also lowered the
      HSP relapse rate during the 3 months of treatment, but did not alter the outcome
      of nephritis at the end of follow up. CONCLUSIONS: Add-on therapy with
      montelukast alleviated the symptoms of HSP. HSP may be improved by add-on therapy
      with a leukotriene receptor antagonist.

PMID- 24299022
TI  - Fungicide field concentrations exceed FOCUS surface water predictions: urgent
      need of model improvement.
AB  - FOCUS models are used in European regulatory risk assessment to predict the
      frequency and magnitude of individual pesticide surface water concentrations. A
      recent study showed that these models are not protective in the prediction of
      insecticide concentrations in surface waters and sediments. Since fungicides
      differ with regard to their physicochemical properties, application patterns, and
      entry routes, we compared a larger data set of 417 measured field concentrations
      (MFC) of agricultural fungicides in surface waters and sediments from 56 studies
      to the respective predicted environmental concentrations (PEC) calculated with
      FOCUS step 1-4. Although the fraction of the underestimation of fungicide MFC
      values was generally lower than that obtained for insecticides, 12% of step 3 and
      23% of step 4 PECs were exceeded by surface water MFCs. Taking only the 90th
      percentile concentration of every substance and only E.U. studies into account
      (E.U. studies: n = 327; 90th percentile + E.U. studies: n = 136), a maximum of
      25% of the step 3 and 43% of the step 4 PECs were exceeded by surface water MFCs,
      which is an even worse outcome than that obtained for insecticides. Our results
      demonstrate that FOCUS predictions are neither protective nor appropriate for
      predicting fungicide concentrations in the field in the context of European
      pesticide risk assessment. 

PMID- 24299023
TI  - National inventory of core capabilities for pandemic influenza preparedness and
      response: results from 36 countries with reviews in 2008 and 2010.
AB  - BACKGROUND: Re-emergence in 2003 of human cases of avian H5N1 and the resultant
      spread of the disease highlighted the need to improve the capacity of countries
      to detect and contain novel viruses. To assess development in this capacity, the
      Centers for Disease Control and Prevention (CDC) produced a tool for assessing a
      country's capability in 12 critical areas related to pandemic preparedness,
      including monitoring and identifying novel influenza viruses. OBJECTIVES:
      Capabilities the CDC tool assesses range from how well a country has planned and
      is prepared for an outbreak to how prepared a country is to respond when a
      pandemic occurs. Included in this assessment tool are questions to determine
      whether a country has a detailed preparedness plan and the laboratory capacity to
      identify various strains of influenza quickly and accurately. METHODS: The tool
      was used first in 2008 when 40 countries in collaboration with CDC calculated
      baseline scores and used a second time in 2010 by 36 of the original 40 countries
      to determine whether they had improved their preparedness. Using basic
      mathematical comparison and statistical analyses, we compared data at the
      aggregate capability level as well as at the indicator and country levels.
      Additionally, we examined the comments of respondents to the assessment
      questionnaire for reasons (positive and negative) that would explain changes in
      scores from 2008 to 2010. RESULTS: Analysis of results of two assessments in 36
      countries shows statistically significant improvement in all 12 capabilities on
      an aggregate level and 47 of 50 indicators.

PMID- 24299024
TI  - The measurement of tissue interface pressures and changes in jugular venous
      parameters associated with cervical immobilisation devices: a systematic review.
AB  - Cervical immobilisation is commonly applied following trauma, particularly blunt
      head injury, but current methods of immobilisation are associated with
      significant complications. Semi-rigid disposable cervical collars are known to
      cause pressure ulcers, and impede effective airway management. These collars may
      also exacerbate a head injury by increasing intracranial pressure as a result of
      external compression of the jugular veins. There is a clear imperative to find
      ways of effectively immobilising the cervical spine whilst minimising
      complications, and any assessment of existing or new devices should include a
      standardized approach to the measurement of tissue interface pressures and their
      effect on jugular venous drainage from the brain. This systematic review
      summarises the research methods and technologies that have been used to measure
      tissue interface pressure and assess the jugular vein in the context of cervical
      immobilisation devices. 27 papers were included and assessed for quality.
      Laboratory investigations and biomechanical studies have gradually given way to
      methods that more accurately reflect clinical care. There are numerous accounts
      of skin ulceration associated with cervical collars, but no standardised approach
      to measuring tissue interface pressure. It is therefore difficult to compare
      studies and devices, but a pressure of less than 30 mmHg appears desirable.
      Cervical collars have been shown to have a compressive effect on the jugular
      veins, but it is not yet certain that this is the cause of the increased
      intracranial pressure observed in association with cervical collar use. This is
      the first review of its type. It will help guide further research in this area of
      trauma care, and the development and testing of new cervical immobilisation
      devices.

PMID- 24299026
TI  - Auxiliary liver transplant is an effective and safe treatment of primary
      hyperoxaluria.

PMID- 24299027
TI  - Crohn's disease: is there a place for neurological screening?
AB  - OBJECTIVE: Neurological complications of inflammatory bowel diseases (IBDs) are
      not rare but are under-diagnosed; some are probably immune-mediated. Several
      previous studies have suggested a higher incidence of demyelinating diseases such
      as multiple sclerosis in IBD patients. In this single-center, prospective,
      observational study, the authors focus on T2 focal white-matter lesions of the
      central nervous system on magnetic resonance imaging (MRI) in IBD patients that
      may be due to demyelination. MATERIAL AND METHODS: A total of 70 patients with
      Crohn's disease were examined before beginning anti-TNF-alpha therapy. These
      patients were treated with azathioprine, mesalazine or both. Patients were
      examined by a neurologist to detect possible signs of demyelinating disease, and
      patients underwent brain MRI (native T1, T2, and FLAIR sequences). RESULTS:
      Thirty-seven patients (53%) exhibited abnormalities on neurological examination,
      and 26 patients (37%) displayed abnormalities on MRI. In seven cases, these MRI
      abnormalities (periventricular lesions) were suspected to be due to
      demyelination. Cerebral spinal fluid investigation (including polyclonal bands)
      was completely negative in five cases and was borderline in one case, and
      multiple sclerosis was confirmed in one case. Pathological MRI findings in 19
      other patients were clinically nonsignificant; most were nonspecific sporadic
      lesions in white matter or mild atrophy. CONCLUSIONS: The results support
      previous data that the frequency of neurological findings in IBD patients is
      generally underestimated. With the extension of biological anti-TNF-alpha
      treatment for IBD, the possibility of a higher risk of developing multiple
      sclerosis should be considered.

PMID- 24299028
TI  - Adult respiratory distress syndrome following cardiac surgery.
AB  - BACKGROUND: Severe lung injury with the development of acute respiratory distress
      syndrome (ARDS) is a serious complication of cardiac surgery. The aim of this
      study was to determine the incidence, risk factors, and mortality of ARDS
      following cardiac surgery. METHODS: We retrospectively analyze data in the period
      between January 2005 and March 2013. RESULTS: Of 6069 patients who underwent
      cardiac surgery during the study period, 37 patients developed ARDS during the
      postoperative period. The incidence of ARDS was 0.61%, with a mortality of 40.5%
      (15 patients). Multivariate regression analysis identified previous cardiac
      surgery, complex cardiac surgery, and more than three transfusions with packed
      red blood cells (PRBC) were independent predictors for developing ARDS.
      CONCLUSIONS: ARDS remains a serious, but very rare complication associated with
      significant mortality. In our study, previous cardiac surgery, complex cardiac
      surgery, and more than three transfusions of PRBC were independent predictors for
      the development of ARDS.

PMID- 24299029
TI  - Acceptorless dehydrogenation of C-C single bonds adjacent to functional groups by
      metal-ligand cooperation.
AB  - Unprecedented direct acceptorless dehydrogenation of C-C single bonds adjacent to
      functional groups to form alpha,beta-unsaturated compounds has been accomplished
      by using a new class of group 9 metal complexes. Metal-ligand cooperation
      operated by the hydroxycyclopentadienyl ligand was proposed to play a major role
      in the catalytic transformation. 

PMID- 24299030
TI  - Fetoscopic single-layer repair of open spina bifida using a cellulose patch:
      preliminary clinical experience.
AB  - OBJECTIVE: To report our preliminary clinical experience in the antenatal
      correction of open spina bifida (OSB) using a fetoscopic approach and a
      simplified closure technique. METHODS: Four fetuses with lumbar-sacral defects
      were operated in utero from 25 to 27 weeks. Surgeries were performed
      percutaneously under general anesthesia using three trocars and partial carbon
      dioxide insufflation. After dissection of the neural placode, the surrounding
      skin was closed over a cellulose patch using a single continuous stitch. RESULTS:
      Surgical closure was successful in three of the four cases. All successful cases
      showed improvement of the hindbrain herniation and no neonatal neurosurgical
      repair was required in two cases. Delivery occurred between 31 and 33 weeks, and
      no fetal or neonatal deaths occurred. Ventriculoperitoneal shunting was not
      needed in two out of the 3 successful cases. CONCLUSIONS: Our preliminary
      experience suggests that definitive fetoscopic repair of OSB is feasible using
      our innovative surgical technique. A phase I trial for the fetoscopic correction
      of OSB with this technique is currently being conducted.

PMID- 24299031
TI  - A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting
      control region in a Beckwith-Wiedemann syndrome patient.
AB  - The IGF2/H19-imprinting control region (ICR1) functions as an insulator to
      methylation-sensitive binding of CTCF protein, and regulates imprinted expression
      of IGF2 and H19 in a parental origin-specific manner. ICR1 methylation defects
      cause abnormal expression of imprinted genes, leading to Beckwith-Wiedemann
      syndrome (BWS) or Silver-Russell syndrome (SRS). Not only ICR1 microdeletions
      involving the CTCF-binding site, but also point mutations and a small deletion of
      the OCT-binding site have been shown to trigger methylation defects in BWS. Here,
      mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation
      defects revealed a novel de novo point mutation of the OCT-binding site on the
      maternal allele in one BWS patient. In BWS, all reported mutations and the small
      deletion of the OCT-binding site, including our case, have occurred within repeat
      A2. These findings indicate that the OCT-binding site is important for
      maintaining an unmethylated status of maternal ICR1 in early embryogenesis. 

PMID- 24299032
TI  - FgFim, a key protein regulating resistance to the fungicide JS399-19, asexual and
      sexual development, stress responses and virulence in Fusarium graminearum.
AB  - Fimbrin is an actin-bundling protein found in intestinal microvilli, hair cell
      stereocilia and fibroblast filopodia. Its homologue Sac6p has been shown to play
      a critical role in endocytosis and diverse cellular processes in Saccharomyces
      cerevisiae. FgFim from the wheat scab pathogenic fungus Fusarium graminearum
      strain Y2021A, which is highly resistant to the fungicide JS399-19, was
      identified by screening a mutant library generated by HPH-HSV-tk cassette
      mediated integration. The functions of FgFim were evaluated by constructing a
      deletion mutant of FgFim, designated DeltaFgFim-15. The deletion mutant exhibited
      a reduced rate of mycelial growth, reduced conidiation, delayed conidium
      germination, irregularly shaped hyphae, a lack of sexual reproduction on
      autoclaved wheat kernels and a dramatic decrease in resistance to JS399-19.
      DeltaFgFim-15 also exhibited increased sensitivity to diverse metal cations, to
      agents that induce osmotic stress and oxidative stress, and to agents that damage
      the cell membrane and cell wall. Pathogenicity assays showed that the virulence
      of the FgFim deletion mutant on flowering wheat heads was impaired, which was
      consistent with its reduced production of the toxin deoxynivalenol in host
      tissue. All of these defects were restored by genetic complementation of the
      mutant with the parental FgFim gene. Quantitative real-time polymerase chain
      reaction (PCR) assays showed that the basal expression of three Cyp51 genes,
      which encode sterol 14alpha-demethylase, was significantly lower in the mutant
      than in the parental strain. The results of this study indicate that FgFim plays
      a critical role in the regulation of resistance to JS399-19 and in various
      cellular processes in F. graminearum. 

PMID- 24299033
TI  - "There comes a time when silence is betrayal": racism and nursing.

PMID- 24299034
TI  - BioPEGylation of polyhydroxybutyrate promotes nerve cell health and migration.
AB  - This study reports on the superior suitability of Polyhydroxybutyrate
      polyethylene glycol hybrid polymers biosynthesised by Cupriavidus necator over
      PHB as biomaterials for tissue engineering. Incorporation of PEG106 (DEG) during
      PHB biosynthesis reduced crystallinity, molecular weight, and hydrophobicity
      while improving mechanical properties. In vitro olfactory ensheathing cell (OEC)
      proliferation was enhanced by cultivation on PHB-b-DEG films. Cultivation on PHB
      and PHB-b-DEG films showed no cytotoxic responses and cell viability and membrane
      integrity was sustained. PHB-b-DEG films promoted OECs entering into the DNA
      replication (S) phase and mitotic (G2-M) phase during the cell growth cycle and
      apoptosis was low. This study also confirmed an association between the level of
      neurite-outgrowth inhibitory protein (Nogo) and receptor pair Ig-like receptor B
      (PirB) expression and cell proliferation, both being down-regulated in cells
      grown on hybrid films when compared with PHB and asynchronous growth. Thus, DEG
      terminated PHB-based biomaterials have great potential as biological scaffolds
      supporting nerve repair. 

PMID- 24299035
TI  - The challenges of improving statistical practice in alcohol treatment research.
AB  - BACKGROUND: This commentary discusses the paper by Hallgren and Witkiewitz (2013)
      which evaluated 5 methods for addressing missing data in clinical trials of
      interventions for alcohol use disorders. The authors conclude that commonly used
      methods (e.g., complete case analysis, single imputation methods) can produce
      misleading results and that better alternatives exist (e.g., multiple imputation
      [MI]). The problems of using inferior approaches are well-known and well
      illustrated by the analysis in this paper, which serves as an educational
      reminder to use more statistically justified practices. METHODS: Findings of this
      paper are put in context of the broader statistical literature. Strategies to
      promote common usage of superior missing data methods are discussed. RESULTS:
      Solving the poor uptake of statistically justified missing data methods will
      require a multilevel diagnosis of the problem and likely a multifaceted response,
      perhaps including the establishment, publication, and enforcement of standards by
      scientific funding and regulatory agencies, scientific journals, and graduate
      program accreditation bodies. CONCLUSIONS: Little disagreement exists regarding
      the importance of addressing missing data in a statistically justified manner
      (e.g., with MI or other maximum likelihood methods). However, as with the
      implementation of other evidence-based practices, knowing what should be done
      does not alone make it happen.

PMID- 24299036
TI  - Comparative analysis of dental implant treatment outcomes following mandibular
      reconstruction with double-barrel fibula bone grafting or vertical distraction
      osteogenesis fibula: a retrospective study.
AB  - PURPOSE: The purpose of this study was twofold: (i) to compare vertical bone
      height (VBH) after tumor resection through grafting with either a double-barrel
      fibula (DBF) technique or vertical distraction osteogenesis of the fibula (VDOF);
      (ii) to compare the performance of loaded dental implants following either DBF or
      VDOF with special focus on implant survival, implant success, and bone
      resorption. MATERIALS AND METHODS: This retrospective clinical study involved 19
      patients who underwent implant placement following DBF (group A, n = 9) or VDOF
      (group B, n = 10) for mandibular reconstruction from March 2006 to May 2008.
      Clinical and radiographic assessments, including VBH, modified Plaque Index
      (mPI), modified Sulcus Bleeding Index (mSBI), and marginal bone level (MBL), were
      taken for both groups after delivery of the final prostheses and annually
      thereafter. RESULTS: Nine patients underwent DBF with 24 implants placed and 10
      patients underwent VDOF with 27 implants placed for mandibular reconstruction
      after tumor resection. Overall, all DBF and VDOF procedures were successful for
      group A and group B. VBH for group A and group B were 20 and 17 mm. There was no
      statistically significant difference of mSBI scores between group A and group B
      in the 3-year follow-up (P = 0.40). In four cases with eight implants of group A
      and two cases with three implants of group B, granulomatous soft tissue grew.
      There was no statistically significant differences of MBL between group A and
      group B in the 3-year follow-up (p = 0.736). The cumulative survival and success
      rates of implants for group A were 100% and 87.5%, and for group B were 100% and
      85.2% in 3-year follow-up, respectively. CONCLUSIONS: On the basis of the study
      of 19 patients who received a total of 51 implants, reconstruction of the
      mandible with DBF flap or VDOF flap, combined with dental implant therapy, was
      considered a predictable option. Compared with implants placed in VDOF bone,
      implants placed in DBF bone had a relative higher incidence of associated
      gingival inflammation. The DBF bone seems more resistant to peri-implant
      resorption processes than VDOF bone during functional loading.

PMID- 24299037
TI  - Organic solvent-free cloud point extraction-like methodology using aggregation of
      graphene oxide.
AB  - Because of its unique properties and capability of formation of well-dispersed
      aqueous colloids in aqueous phase, graphene oxide can be used for the efficient
      preconcentration of heavy metal ions prior to their determination. The complete
      collection of graphene oxide colloids from water has generally been considered to
      be insurmountable. Here, graphene oxide aggregation triggered by introducing NaCl
      was used to develop a novel organic solvent-free cloud point extraction-like
      method for the determination of trace toxic metals. The graphene oxide sheets
      were uniformly dispersed in aqueous samples or standard solutions for a fast and
      efficient adsorption of Pb(II), Cd(II), Bi(III), and Sb(III) owing to its
      hydrophilic character and the electrostatic repulsion among the graphene oxide
      sheets, and its aggregation immediately occurred when the electrostatic repulsion
      was eliminated via adding NaCl to neutralize the excessive negative charges on
      the surface of graphene oxide sheets. The aggregates of graphene oxide and
      analytes ions were separated and treated with hydrochloric acid to form a slurry
      solution. The slurry solution was pumped to mix with KBH4 solution to generate
      hydrides, which were subsequently separated from the liquid phase and directed to
      an atomic fluorescence spectrometer or directly introduced to an inductively
      coupled plasma optical emission spectrometer for detection. On the basis of a 50
      mL sample volume, the limits of detection of 0.01, 0.002, 0.01, and 0.006 ng mL(
      1) were obtained for Pb, Cd, Bi, and Sb, respectively, when using atomic
      fluorescence spectrometry, providing 35-, 8-, 36-, and 37-fold improvements over
      the conventional method. Detection limits of 0.6, 0.15, 0.1, and 1.0 ng mL(-1)
      were obtained with the use of slurry sampling inductively coupled plasma optical
      emission spectrometry. The method was applied for analysis of two Certified
      Reference Materials and three water samples for these elements. 

PMID- 24299038
TI  - Factorial structure and psychometric properties of a brief version of the
      Reminiscence Functions Scale with Chinese older adults.
AB  - OBJECTIVE: The current study aims to examine the factorial structure and
      psychometric properties of a brief version of the Reminiscence Functions Scale
      (RFS), a 14-item assessment tool of reminiscence functions, with Chinese older
      adults. METHOD: The scale, covering four reminiscence functions (boredom
      reduction, bitterness revival, problem solving, and identity) was translated from
      English into Chinese and administered to older adults (N=675). Confirmatory
      factor analysis and hierarchical confirmatory factor analysis were conducted to
      examine its factorial structure, and its psychometric properties and criterion
      validity were examined. RESULTS: Confirmatory factor analysis supports a second
      order model comprising one second-order factor and four first-order factors of
      RFS. The Cronbach's alpha of the subscales ranged from 0.75 to 0.90. CONCLUSION:
      The brief RFS contains a second-order factorial structure. Its psychometric
      properties support it as a sound instrument for measuring reminiscence functions
      among Chinese older adults.

PMID- 24299039
TI  - Factors related to patterns of body mass index in early infancy: 18 month
      longitudinal study.
AB  - BACKGROUND: Children with early adiposity rebound (AR), measured using individual
      body mass index (BMI) growth curves, have an increased risk of metabolic disease
      as adults. The children with early AR, however, are not fully characterized. The
      aim of this study was to investigate the prevalence and characteristics of the
      infants who develop early AR. METHODS: A total of 1248 full-term children and
      their mothers participated in the present study. Pre-pregnancy, prenatal, birth,
      4 month and 18 month records were collected. Children were classified into two
      groups: a decrease (D) group, in which the 18 month BMI was lower than the 4
      month BMI (n = 1097), in keeping with the standard BMI percentile curve, and an
      increase (I) group, in which the 18 month BMI was higher than the 4 month BMI (n
      = 151). RESULTS: Although children in both groups had similar body size at birth,
      those in the I group had a lower weight at 4 months and higher weight at 18
      months than those in the D group (P < 0.001). Fewer mothers in the I group
      exclusively breast-fed their infants (P = 0.012). These characteristics of
      infants in the I group suggested a pattern of low fatness level followed by rapid
      increased fat gain. CONCLUSIONS: Approximately 10% (151/1248) of infants did not
      follow the standard BMI percentile curves between 4 months and 18 months of age.
      They were more likely not to be exclusively breast-fed. This finding further
      stresses the importance of breast-feeding in early infancy.

PMID- 24299040
TI  - Ultrathin MoS2 nanoplates with rich active sites as highly efficient catalyst for
      hydrogen evolution.
AB  - Well-defined ultrathin MoS2 nanoplates are developed by a facile solvent
      dependent control route from single-source precursor for the first time. The
      obtained ultrathin nanoplate with a thickness of ~ 5 nm features high density of
      basal edges and abundant unsaturated active S atoms. The multistage growth
      process is investigated and the formation mechanism is proposed. Ultrathin MoS2
      nanoplates exhibit an excellent activity for hydrogen evolution reaction (HER)
      with a small onset potential of 0.09 V, a low Tafel slope of 53 mV dec(-1), and
      remarkable stability. This work successfully demonstrates that the introduction
      of unsaturated active S atoms into ultrathin MoS2 nanoplates for enhanced
      electrocatalytic properties is feasible through a facial one-step solvent control
      method, and that this may open up a potential way for designing more efficient
      MoS2-based catalysts for HER.

PMID- 24299041
TI  - Porous media-induced aggregation of protein-stabilized gold nanoparticles.
AB  - Gold-nanoparticles (AuNPs) are employed for cancer treatment, drug delivery,
      chemical analyses, and many other uses. As AuNP manufacture increases, it is
      imperative that we understand the environmental fate of these nanomaterials. We
      investigated the transport and stability of AuNPs under simulated groundwater
      conditions. Batch experiments indicated that 16 nm AuNPs stabilized with bovine
      serum albumin (BSA-cit-AuNPs) was slightly more stable under high ionic strength
      conditions than citrate-functionalized AuNPs (cit-AuNPs) of the same core size.
      Both types of AuNPs were injected into glass bead-packed columns and subjected to
      transport with varying NaCl and CaCl2 concentrations. BSA-cit-AuNPs deposited
      less than cit-AuNPs in the presence of increasing concentrations of CaCl2, but
      the opposite trend was observed in the presence of increasing concentrations of
      NaCl. This finding differed from the results obtained in the batch studies.
      Calculated attachment efficiencies (alpha) failed to reflect the observed
      experimental column data, with alpha at maximum only approaching 0.1 even though
      a majority of the AuNPs were retained in the column. Colloid filtration theory
      fails to predict and explain this discrepancy. We conclude that media induced
      nanoparticle aggregation is responsible for the inconsistency. 

PMID- 24299042
TI  - Tailoring the optical characteristics of microsized InP nanoneedles directly
      grown on silicon.
AB  - Nanoscale self-assembly offers a pathway to realize heterogeneous integration of
      III-V materials on silicon. However, for III-V nanowires directly grown on
      silicon, dislocation-free single-crystal quality could only be attained below
      certain critical dimensions. We recently reported a new approach that overcomes
      this size constraint, demonstrating the growth of single-crystal InGaAs/GaAs and
      InP nanoneedles with the base diameters exceeding 1 MUm. Here, we report distinct
      optical characteristics of InP nanoneedles which are varied from mostly
      zincblende, zincblende/wurtzite-mixed, to pure wurtzite crystalline phase. We
      achieved, for the first time, pure single-crystal wurtzite-phase InP nanoneedles
      grown on silicon with bandgaps of 80 meV larger than that of zincblende-phase
      InP. Being able to attain excellent material quality while scaling up in size
      promises outstanding device performance of these nanoneedles. At room
      temperature, a high internal quantum efficiency of 25% and optically pumped
      lasing are demonstrated for single nanoneedle as-grown on silicon substrate.
      Recombination dynamics proves the excellent surface quality of the InP
      nanoneedles, which paves the way toward achieving multijunction photovoltaic
      cells, long-wavelength heterostructure lasers, and advanced photonic integrated
      circuits. 

PMID- 24299044
TI  - Final hard copy issue of the Scandinavian Journal of Primary Health Care--online
      only from 2014.

PMID- 24299043
TI  - Selecting informative subsets of sparse supermatrices increases the chance to
      find correct trees.
AB  - BACKGROUND: Character matrices with extensive missing data are frequently used in
      phylogenomics with potentially detrimental effects on the accuracy and robustness
      of tree inference. Therefore, many investigators select taxa and genes with high
      data coverage. Drawbacks of these selections are their exclusive reliance on data
      coverage without consideration of actual signal in the data which might, thus,
      not deliver optimal data matrices in terms of potential phylogenetic signal. In
      order to circumvent this problem, we have developed a heuristics implemented in a
      software called mare which (1) assesses information content of genes in
      supermatrices using a measure of potential signal combined with data coverage and
      (2) reduces supermatrices with a simple hill climbing procedure to submatrices
      with high total information content. We conducted simulation studies using
      matrices of 50 taxa * 50 genes with heterogeneous phylogenetic signal among genes
      and data coverage between 10-30%. RESULTS: With matrices of 50 taxa * 50 genes
      with heterogeneous phylogenetic signal among genes and data coverage between 10
      30% Maximum Likelihood (ML) tree reconstructions failed to recover correct trees.
      A selection of a data subset with the herein proposed approach increased the
      chance to recover correct partial trees more than 10-fold. The selection of data
      subsets with the herein proposed simple hill climbing procedure performed well
      either considering the information content or just a simple presence/absence
      information of genes. We also applied our approach on an empirical data set,
      addressing questions of vertebrate systematics. With this empirical dataset
      selecting a data subset with high information content and supporting a tree with
      high average boostrap support was most successful if information content of genes
      was considered. CONCLUSIONS: Our analyses of simulated and empirical data
      demonstrate that sparse supermatrices can be reduced on a formal basis
      outperforming the usually used simple selections of taxa and genes with high data
      coverage.

PMID- 24299045
TI  - Partners of cancer patients consult their GPs significantly more often with both
      somatic and psychosocial problems.
AB  - OBJECTIVE: Partners of cancer patients experience psychological distress and
      impaired physical health around and after the diagnosis of cancer. It is unknown
      whether these problems are presented to the general practitioner (GP). This study
      aimed to establish partners' GP use around the diagnosis of cancer. DESIGN:
      Cohort study. SETTING: Primary care. SUBJECTS: Partners of 3071 patients with
      breast, prostate, colorectal, or lung cancer were included. Patients were
      diagnosed in 2001-2009 and were alive at least two years after diagnosis. MAIN
      OUTCOME MEASURES: Number of GP contacts and health problems in partners between
      six months before and two years after diagnosis. RESULTS: In the first six months
      after diagnosis, partners' GP use was similar to baseline (18 to six months
      before diagnosis). Between six and 24 months after diagnosis, GP use was
      increased in partners of patients with breast, prostate, and colorectal cancer,
      an increase of 31% (p = 0.001), 26% (p = 0.001), and 19% (p = 0.042),
      respectively. In partners of patients with breast cancer and colorectal cancer,
      GP use was increased for both somatic and psychosocial symptoms. In partners of
      prostate cancer patients, an increase was seen in somatic symptoms, whereas in
      partners of lung cancer patients, GP use was only increased for psychosocial
      symptoms. "Problems with the illness of the partner" was a frequently recorded
      reason for contact in the first six months after diagnosis. CONCLUSION: GP use of
      partners of cancer patients is increased 6-24 months after diagnosis, but health
      problems vary between cancer types. GPs should be alert for somatic and
      psychosocial problems in partners of cancer patients.

PMID- 24299046
TI  - Barriers and facilitators for general practitioners to engage in advance care
      planning: a systematic review.
AB  - OBJECTIVE: The aim of this systematic review is to identify the perceived factors
      hindering or facilitating GPs in engaging in advance care planning (ACP) with
      their patients about care at the end of life. DESIGN: Studies from 1990 to 2011
      were found in four electronic databases (PubMed, CINAHL, EMBASE, PsycINFO); by
      contacting first authors of included studies and key experts; and searching
      through relevant journals and reference lists. Studies were screened, graded for
      quality, and analysed independently by two authors; those reporting the
      perception by GPs of barriers and facilitators to engagement in ACP were
      included. RESULTS: Eight qualitative studies and seven cross-sectional studies
      were included for data extraction. All barriers and facilitators identified were
      categorized as GP characteristics, perceived patient factors, or health care
      system characteristics. Stronger evidence was found for the following barriers:
      lack of skills to deal with patients' vague requests, difficulties with defining
      the right moment, the attitude that it is the patient who should initiate ACP,
      and fear of depriving patients of hope. Stronger evidence was found for the
      following facilitators: accumulated skills, the ability to foresee health
      problems in the future, skills to respond to a patient's initiation of ACP,
      personal convictions about who to involve in ACP, and a longstanding patient-GP
      relationship and the home setting. CONCLUSION: Initiation of ACP in general
      practice may be improved by targeting the GPs' skills, attitudes, and beliefs but
      changes in health care organization and financing could also contribute.

PMID- 24299047
TI  - Long-term follow-up of patients with elevated serum calcium concentrations in
      Swedish primary care.
AB  - OBJECTIVE: To follow up patients with elevated calcium concentrations after 10
      years. DESIGN: Longitudinal, using medical records, questionnaires, and clinical
      investigation. SETTING: Primary care in Tibro, Sweden, 2008-2010. SUBJECTS: 127
      patents with elevated calcium concentrations and 254 patients with normal calcium
      concentrations from the local community, attending the health care centre. MAIN
      OUTCOME MEASURES: Diagnoses and mortality in patients with elevated calcium
      concentrations in 1995-2000, compared with patients with normal calcium
      concentrations and the background population. RESULTS: The proportion of patients
      for whom no underlying cause was detected decreased from 55% at baseline to 12%
      at follow-up. Primary hyperparathyroidism was most common in women, 23% at
      baseline and 36% at follow-up, and the cancer prevalence increased from 5% to 12%
      in patients with elevated calcium concentration. Mortality tended to be higher in
      men with elevated calcium concentrations compared with men with normal calcium
      concentrations, and was significantly higher than in the background population
      (SMR 2.3, 95% CI 1.3-3.8). Cancer mortality was significantly increased in men (p
      = 0.039). Low calcium concentrations were also associated with higher mortality
      (p = 0.004), compared with patients with normal calcium concentrations.
      CONCLUSION: This study underscores the importance of investigating patients with
      increased calcium concentrations suggesting that most of these patients--88% in
      our study--will turn out to have an underlying disease associated with
      hypercalcaemia during a 10-year follow-up period. Elevated calcium concentrations
      had a different disease pattern in men and women, with men showing increased
      cancer mortality in this study.

PMID- 24299048
TI  - Direct visualization of Agrobacterium-delivered VirE2 in recipient cells.
AB  - Agrobacterium tumefaciens is a natural genetic engineer widely used to deliver
      DNA into various recipients, including plant, yeast and fungal cells. The
      bacterium can transfer single-stranded DNA molecules (T-DNAs) and bacterial
      virulence proteins, including VirE2. However, neither the DNA nor the protein
      molecules have ever been directly visualized after the delivery. In this report,
      we adopted a split-GFP approach: the small GFP fragment (GFP11) was inserted into
      VirE2 at a permissive site to create the VirE2-GFP11 fusion, which was expressed
      in A. tumefaciens; and the large fragment (GFP1-10) was expressed in recipient
      cells. Upon delivery of VirE2-GFP11 into the recipient cells, GFP fluorescence
      signals were visualized. VirE2-GFP11 was functional like VirE2; the GFP fusion
      movement could indicate the trafficking of Agrobacterium-delivered VirE2. As the
      natural host, all plant cells seen under a microscope received the VirE2 protein
      in a leaf-infiltration assay; most of VirE2 moved at a speed of 1.3-3.1 MUm sec-1
      in a nearly linear direction, suggesting an active trafficking process. Inside
      plant cells, VirE2-GFP formed filamentous structures of different lengths, even
      in the absence of T-DNA. As a non-natural host recipient, 51% of yeast cells
      received VirE2, which did not move inside yeast. All plant cells seen under a
      microscope transiently expressed the Agrobacterium-delivered transgene, but only
      0.2% yeast cells expressed the transgene. This indicates that Agrobacterium is a
      more efficient vector for protein delivery than T-DNA transformation for a non
      natural host recipient: VirE2 trafficking is a limiting factor for the genetic
      transformation of a non-natural host recipient. The split-GFP approach could
      enable the real-time visualization of VirE2 trafficking inside recipient cells.

PMID- 24299049
TI  - Drug susceptibility surveillance of influenza viruses circulating in the United
      States in 2011-2012: application of the WHO antiviral working group criteria.
AB  - BACKGROUND: Assessing susceptibility of influenza viruses to neuraminidase (NA)
      inhibitors (NAIs) is primarily done in NA inhibition (NI) assays, supplemented by
      NA sequence analysis. However, two factors present challenges for NI assay data
      interpretation: lack of established IC50 values indicative of clinically relevant
      resistance and insufficient harmonization of NI testing methodologies among
      surveillance laboratories. In 2012, the WHO working group on influenza antiviral
      susceptibility (WHO-AVWG) developed criteria to facilitate consistent
      interpretation and reporting of NI assay data. METHODS: The WHO-AVWG
      classification criteria were applied in interpreting NI assay data for two FDA
      licensed NAIs, oseltamivir and zanamivir, for viruses collected in the United
      States during the 2011-2012 winter season. RESULTS: All A (H1N1)pdm09 viruses (n
      = 449) exhibited normal inhibition by oseltamivir and zanamivir, with the
      exception of eight viruses (1.8%) with highly reduced inhibition by oseltamivir,
      which carried the H275Y marker of oseltamivir resistance. A (H3N2) viruses (n =
      978) exhibited normal inhibition by both NAIs, except for one virus with highly
      reduced inhibition by zanamivir due to the cell culture-selected NA change,
      Q136K. Type B viruses (n = 343) exhibited normal inhibition by both drugs, except
      for an isolate with reduced inhibition by both NAIs that had the cell culture
      selected A200T substitution. CONCLUSIONS: WHO-AVWG classification criteria
      allowed the detection of viruses carrying the established oseltamivir resistance
      marker, as well as viruses whose susceptibility was altered during propagation.
      These criteria were consistent with statistical-based criteria for detecting
      outliers and will be useful in harmonizing NI assay data among surveillance
      laboratories worldwide and in establishing laboratory correlates of clinically
      relevant resistance.

PMID- 24299050
TI  - The effect of protein timing on muscle strength and hypertrophy: a meta-analysis.
AB  - Protein timing is a popular dietary strategy designed to optimize the adaptive
      response to exercise. The strategy involves consuming protein in and around a
      training session in an effort to facilitate muscular repair and remodeling, and
      thereby enhance post-exercise strength- and hypertrophy-related adaptations.
      Despite the apparent biological plausibility of the strategy, however, the
      effectiveness of protein timing in chronic training studies has been decidedly
      mixed. The purpose of this paper therefore was to conduct a multi-level meta
      regression of randomized controlled trials to determine whether protein timing is
      a viable strategy for enhancing post-exercise muscular adaptations. The strength
      analysis comprised 478 subjects and 96 ESs, nested within 41 treatment or control
      groups and 20 studies. The hypertrophy analysis comprised 525 subjects and 132
      ESs, nested with 47 treatment or control groups and 23 studies. A simple pooled
      analysis of protein timing without controlling for covariates showed a small to
      moderate effect on muscle hypertrophy with no significant effect found on muscle
      strength. In the full meta-regression model controlling for all covariates,
      however, no significant differences were found between treatment and control for
      strength or hypertrophy. The reduced model was not significantly different from
      the full model for either strength or hypertrophy. With respect to hypertrophy,
      total protein intake was the strongest predictor of ES magnitude. These results
      refute the commonly held belief that the timing of protein intake in and around a
      training session is critical to muscular adaptations and indicate that consuming
      adequate protein in combination with resistance exercise is the key factor for
      maximizing muscle protein accretion. 

PMID- 24299051
TI  - Considerations of reliability and validity of transplant center report cards.

PMID- 24299052
TI  - Comparison of the accuracy of CT colonography and colonoscopy in the diagnosis of
      colorectal cancer.
AB  - AIM: The available evidence was reviewed to compare the effectiveness of CT
      colonography with that of colonoscopy for colorectal cancer (CRC) screening.
      METHOD: An electronic search was conducted using PubMed, EMBASE, the Cochrane
      Library and Centre for Reviews and Dissemination databases, from inception to
      July 2009. Studies were included if investigations used CT colonography for CRC
      screening in asymptomatic populations. Studies were excluded if investigations
      were conducted for the diagnosis of CRC or in elderly, high-risk or symptomatic
      populations. RESULTS: Of the 213 references identified, nine studies were
      included. The specificity of CT colonography in screening for CRC was high,
      although it decreased with decreasing diameter of polyp to be detected. The
      sensitivity of CT colonography for the detection of polyps < 6 mm in diameter was
      low and heterogeneous, although it was higher for polyps > 10 mm. The main
      factors contributing to a greater sensitivity of CT colonography were the
      inclusion of only populations with an average CRC risk and colonic insufflation
      with CO2 . The incidence of adverse effects was very low for both tests.
      CONCLUSION: CT colonography has high specificity but heterogeneous sensitivity,
      although in most cases it is not as sensitive or specific as conventional
      colonoscopy. CT colonography could therefore be useful as a screening test for
      populations with an average risk of CRC.

PMID- 24299053
TI  - Is happiness good for your personality? Concurrent and prospective relations of
      the big five with subjective well-being.
AB  - The present research examined longitudinal relations of the Big Five personality
      traits with three core aspects of subjective well-being: life satisfaction,
      positive affect, and negative affect. Latent growth models and autoregressive
      models were used to analyze data from a large, nationally representative sample
      of 16,367 Australian residents. Concurrent and change correlations indicated that
      higher levels of subjective well-being were associated with higher levels of
      Extraversion, Agreeableness, and Conscientiousness, and with lower levels of
      Neuroticism. Moreover, personality traits prospectively predicted change in well
      being, and well-being levels prospectively predicted personality change.
      Specifically, prospective trait effects indicated that individuals who were
      initially extraverted, agreeable, conscientious, and emotionally stable
      subsequently increased in well-being. Prospective well-being effects indicated
      that individuals with high initial levels of well-being subsequently became more
      agreeable, conscientious, emotionally stable, and introverted. These findings
      challenge the common assumption that associations of personality traits with
      subjective well-being are entirely, or almost entirely, due to trait influences
      on well-being. They support the alternative hypothesis that personality traits
      and well-being aspects reciprocally influence each other over time. 

PMID- 24299054
TI  - Replacement of the extracardiac conduit for infective endocarditis after a fontan
      operation.
AB  - We report the management of infective endocarditis after an extracardiac Fontan
      operation. Obstruction of the infected conduit and the associated pulmonary
      arterial embolism led to failure of the Fontan circulation. This was managed by
      completely removing both the infected conduit and emboli and replacing the
      conduit.

PMID- 24299055
TI  - Active Helicobacter pylori infection is associated with colorectal mucosa
      adenomatous polyp--early and advanced adenocarcinoma sequence.

PMID- 24299056
TI  - Spectral domain macular optical coherence tomography: a new diagnostic tool for
      glaucoma?

PMID- 24299057
TI  - The risks and outcome of pregnancy in an advanced maternal age in oocyte donation
      cycles.
AB  - The maternal age at the first and repeated deliveries constantly rises in
      developed countries due to current social trends that favor values of personal
      achievements upon procreation. Assisted reproduction technologies and especially
      the availability of oocyte donation programs extend the age of fecundity to the
      fifth and sixth decades of life. The ability to conceive and deliver at such age
      raises serious medical, moral, social and legal concerns regarding the health and
      welfare of the mother and child will be presented and discussed here.

PMID- 24299058
TI  - From frog integument to human skin: dermatological perspectives from frog skin
      biology.
AB  - For over a century, frogs have been studied across various scientific fields,
      including physiology, embryology, neuroscience, (neuro)endocrinology, ecology,
      genetics, behavioural science, evolution, drug development, and conservation
      biology. In some cases, frog skin has proven very successful as a research model,
      for example aiding in the study of ion transport through tight epithelia, where
      it has served as a model for the vertebrate distal renal tubule and mammalian
      epithelia. However, it has rarely been considered in comparative studies
      involving human skin. Yet, despite certain notable adaptations that have enabled
      frogs to survive in both aquatic and terrestrial environments, frog skin has many
      features in common with human skin. Here we present a comprehensive overview of
      frog (and toad) skin ontogeny, anatomy, cytology, neuroendocrinology and
      immunology, with special attention to its unique adaptations as well as to its
      similarities with the mammalian integument, including human skin. We hope to
      provide a valuable reference point and a source of inspiration for both amphibian
      investigators and mammalian researchers studying the structural and functional
      properties of the largest organ of the vertebrate body. 

PMID- 24299059
TI  - Activin A regulates growth of gastro-intestinal epithelial cells by mediating
      epithelial-mesenchymal interaction.
AB  - The importance of epithelial-mesenchymal interaction on the development of gastro
      intestinal (GI) organs has been repeatedly reported, but its molecular mechanism
      has not been fully understood though several factors including hepatocyte growth
      factor and endothelin-3 have been shown to mediate it. Activins have been
      demonstrated to play important roles in the regulation of organogenesis in
      vertebrates, but their roles in the regulation of growth and differentiation of
      GI organs remain to be solved. In the present study, we examined expression of
      activins in developing rat GI tract, and found that inhibin bA encoding activin A
      was specifically expressed by GI mesenchymes, while inhibin bB encoding activin B
      was expressed by both epithelial and mesenchymal components. We then examined the
      effect of activin A on the growth of fetal rat GI epithelial cells in primary
      culture. We found that activin A inhibited the growth of forestomach and
      glandular stomach epithelial cells while it stimulated the growth of colonic
      epithelial cells. These results suggest that activin A secreted from GI
      mesenchymes region-specifically regulates the growth of attaching epithelial
      cells. We thus conclude that activin A mediates epithelial-mesenchymal
      interaction in the developing GI tract. 

PMID- 24299060
TI  - Comparison between laparotomy first versus angiographic embolization first in
      patients with pelvic fracture and hemoperitoneum: a nationwide observational
      study from the Japan Trauma Data Bank.
AB  - BACKGROUND: A common dilemma in the management of pelvic fractures is recognizing
      the presence of associated abdominal injury. The purpose of this study was to
      determine the association between initial therapeutic intervention (laparotomy or
      transcatheter arterial embolization (TAE)) and mortality. METHODS: This was a
      cohort study using the Japan Trauma Data Bank between 2004 and 2010, including
      blunt trauma patients with pelvic fractures and positive Focused Assessment with
      Sonography in Trauma (FAST) results. Eligible patients were restricted to those
      who underwent laparotomy or TAE/angiography as the initial therapeutic
      intervention. Crude and adjusted odds ratio (AOR) for in-hospital mortality were
      compared between the laparotomy first and TAE first groups (reference group).
      Multiple logistic regression analysis and propensity score adjusted analysis were
      used to adjust for clinically relevant confounders, including the severity of
      injury. RESULTS: Of the 317 participants, 123 patients underwent laparotomy first
      and 194 patients underwent TAE first. The two groups were similar in terms of
      age, although the laparotomy first group had higher mean Injury Severity Scores
      (ISS) and higher mean scores based on the abdominal Abbreviated Injury Scale
      (AIS), as well as lower mean pelvic AIS and systolic blood pressure (SBP). Half
      of the patients who were hypotensive (SBP < 90 mmHg) on arrival underwent TAE
      first. The laparotomy first group had a significantly higher crude in-hospital
      mortality (41% vs. 27%; P < 0.01). After adjusting for confounders, the choice of
      initial therapeutic intervention did not affect the in-hospital mortality (AOR,
      1.20; 95% Confidence Interval (CI), 0.61-2.39). Even in the limited subgroup of
      hypotensive patients (SBP 66-89 mmHg and SBP < 65 mmHg subgroup), the effect was
      similar (AOR, 1.50; 95% CI, 0.56-4.05 and AOR, 1.05; 95% CI, 0.44-3.03).
      CONCLUSIONS: In Japan, laparotomy and TAE are equally chosen as the initial
      therapeutic intervention regardless of hemodynamic status. No significant
      difference was seen between the laparotomy first and TAE first groups regarding
      in-hospital mortality.

PMID- 24299062
TI  - The importance of measurement precision and behavioral homologies in evaluating
      the behavioral consequences of fetal-ethanol exposure: commentary on Williams and
      colleagues ("Sensory-motor deficits in children with fetal alcohol spectrum
      disorder assessed using a robotic virtual reality platform").
AB  - The recent study by Willams and colleagues utilized a novel robotic virtual
      reality measurement system to measure sensory-motor processing deficits in
      children with fetal alcohol spectrum disorders (FASDs). This system and the
      precise quantitation of distinct constituent behavioral processes may hold
      considerable utility and importance for the study of FASD-related motor deficits,
      their neural bases, and translational research efforts using homologous
      behavioral approaches in animal and human studies.. 

PMID- 24299063
TI  - Effects of titanium brush on machined and sand-blasted/acid-etched titanium disc
      using confocal microscopy and contact profilometry.
AB  - OBJECTIVE: Mechanical techniques, including scaling with metal, plastic, or
      ultrasonic instruments, rubber cup polishing, air-powder abrasive system and
      brushing with a conventional or a rotating brush, have been used for the
      debridement of dental implants. Recently, rotating brushes with titanium bristles
      (titanium brush) have been introduced for the debridement of implant surface when
      peri-implant osseous defects occur. The purpose of this study was to evaluate the
      effects of a titanium brush on machined (MA) and sand-blasted and acid-etched
      (SA) titanium surfaces using scanning electron microscopy, confocal microscopy
      and profilometry. Moreover, correlations between the two quantitative evaluation
      methods (confocal microscopy and contact profilometry) were assessed. MATERIALS
      AND METHODS: Both MA and SA discs were treated with rotating titanium brush at
      300 rpm under irrigation for a total of 40 s. Roughness measurements were taken
      with confocal microscopy and surface profilometry. Then, the MA and SA surfaces
      were evaluated using scanning electron microscopy to determine the changes of the
      surface properties. RESULTS: Untreated MA surface demonstrated uniform roughness
      with circumferential machining marks, and scratch lines over the original
      surfaces were observed after treatment with the titanium brush. Similarly, the
      titanium brush produced noticeable changes on the SA titanium surfaces. However,
      this treatment with titanium brush did not significantly change the roughness
      parameters, including the arithmetic mean height of the surface (Sa) and the
      maximum height of the surface (Sz), in both MA and SA surfaces. Correlations
      between two evaluation methods showed a Pearson correlation coefficient of 0.98
      with linear regression R(2) of 0.96. CONCLUSION: This study showed that the
      treatment with the titanium brush did not significantly change the roughness
      parameters, including Sa and Sz, in both MA and SA surfaces. Correlations between
      confocal microscopy and surface profilometry showed high correlation with a
      Pearson correlation coefficient of 0.98.

PMID- 24299064
TI  - Hemin/G-quadruplex-catalyzed aerobic oxidation of thiols to disulfides:
      application of the process for the development of sensors and aptasensors and for
      probing acetylcholine esterase activity.
AB  - This study describes the novel hemin/G-quadruplex DNAzyme-catalyzed aerobic
      oxidation of thiols to disulfides and the respective mechanism. The mechanism of
      the reaction involves the DNAzyme-catalyzed oxidation of thiols to disulfides and
      the thiol-mediated autocatalytic generation of H2O2 from oxygen. The coupling of
      a concomitant H2O2-mediated hemin/G-quadruplex-catalyzed oxidation of Amplex Red
      to the fluorescent resorufin as a transduction module provides a fluorescent
      signal for probing the catalyzed oxidation of the thiol to disulfides and for
      probing sensing processes that yield the hemin/G-quadruplex as a functional
      label. Accordingly, a versatile sensing method for analyzing thiols (L-cysteine,
      glutathione) using the H2O2-mediated DNAzyme-catalyzed oxidation of Amplex Red to
      the resorufin was developed. Also, the L-cysteine and Amplex Red system was
      implemented as an auxiliary fluorescent transduction module for probing
      recognition events that form the catalytic hemin/G-quadruplex structures. This is
      exemplified with the development of thrombin aptasensor. The thrombin/thrombin
      binding aptamer recognition complex binds hemin, and the resulting catalytic
      complex activates the auxiliary transduction module, involving the aerobic
      oxidation of l-cysteine and the concomitant formation of the fluorescent
      resorufin. Finally, the hemin/G-quadruplex DNAzyme/Amplex Red system was used to
      follow the activity of acetylcholine esterase, AChE, and to probe its inhibition.
      The AChE-catalyzed hydrolysis of acetylthiocholine to the thiol-functionalized
      thiocholine enabled the probing of the enzymatic activity of AChE through the
      hemin/G-quadruplex-catalyzed aerobic oxidation of thiocholine to the respective
      disulfide and the concomitant generation of the fluorescent resorufin product.

PMID- 24299065
TI  - Unexplained double-chambered left ventricle associated with contracting right
      ventricular aneurysm and right atrial enlargement.
AB  - In this article, we describe a double-chambered left ventricle (LV) associated
      with a functional right ventricular (RV) aneurysm and right atrial (RA)
      enlargement in an asymptomatic 24-year-old woman with a family history of sudden
      cardiac death. We will discuss the differential diagnosis, genetic testing and
      possible prognostic implications. 

PMID- 24299066
TI  - MosaicIA: an ImageJ/Fiji plugin for spatial pattern and interaction analysis.
AB  - BACKGROUND: Analyzing spatial distributions of objects in images is a fundamental
      task in many biological studies. The relative arrangement of a set of objects
      with respect to another set of objects contains information about potential
      interactions between the two sets of objects. If they do not "feel" each other's
      presence, their spatial distributions are expected to be independent of one
      another. Spatial correlations in their distributions are indicative of
      interactions and can be modeled by an effective interaction potential acting
      between the points of the two sets. This can be used to generalize co
      localization analysis to spatial interaction analysis. However, no user-friendly
      software for this type of analysis was available so far. RESULTS: We present an
      ImageJ/Fiji plugin that implements the complete workflow of spatial pattern and
      interaction analysis for spot-like objects. The plugin detects objects in images,
      infers the interaction potential that is most likely to explain the observed
      pattern, and provides statistical tests for whether an inferred interaction is
      significant given the number of objects detected in the images and the size of
      the space within which they can distribute. We benchmark and demonstrate the
      present software using examples from confocal and PALM single-molecule
      microscopy. CONCLUSIONS: The present software greatly simplifies spatial
      interaction analysis for point patterns, and makes it available to the large user
      community of ImageJ and Fiji. The presented showcases illustrate the usage of the
      software.

PMID- 24299067
TI  - Fractionated radioimmunotherapy with 90Y-labeled fully human anti-CEA antibody.
AB  - Carcinoembryonic antigen (CEA) is an attractive target molecule of
      radioimmunotherapy (RIT). To enhance RIT's therapeutic efficacy, the
      fractionation of radiolabeled antibody doses is an attractive strategy. In this
      study, a fully human anti-CEA monoclonal antibody (mAb) C2-45 was selected by
      virtue of its lack of immunogenicity, and the effectiveness of fractionated RIT
      with yttrium-90 (90Y)-labeled mAb C2-45 was evaluated. In LS180 tumor-bearing
      mice, indium-111 (111In)-labeled mAb C2-45 showed high and persistent tumor
      accumulation. Therapeutic studies were performed with single doses of 90Y-mAb C2
      45 (100 or 200 MUCi) or double doses of 100 MUCi 90Y-mAb C2-45 at different
      intervals (5, 10, and 15 days). All 90Y-mAb C2-45-treated mice showed inhibition
      of tumor progression, while the time to tumor progression was much longer in both
      the 200-MUCi-treated group and the double 100-MUCi-treated group than in the
      single 100-MUCi-treated group. The therapeutic effect of the double 100 MUCi
      administration at days 0 and 15 lasted significantly longer than that in the
      other treatment groups. These findings indicate that 90Y-mAb C2-45 may be a
      promising agent for the treatment of CEA-positive cancer and that the
      fractionation of 90Y-labeled antibody doses could enhance the therapeutic effect
      if performed according to an appropriate protocol.

PMID- 24299068
TI  - Clustering chlorine reactivity of haloacetic acid precursors in inland lakes.
AB  - Dissolved organic matter (DOM) represents the major pool of organic precursors
      for harmful disinfection byproducts, such as haloacetic acids (HAAs), formed
      during drinking water chlorination, but much of it remains molecularly
      uncharacterized. Knowledge of model precursors is thus a prerequisite for
      understanding the more complex whole water DOM. The utility of HAA formation
      potential data from model DOM precursors, however, is limited due to the lack of
      comparability to water samples. In this study, the formation kinetics of
      dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two predominant
      HAA species, were delineated upon chlorination of seventeen model DOM precursors
      and sixty-eight inland lake water samples collected from the Upper Midwest region
      of the United States. Of particular interest was the finding that the DCAA and
      TCAA formation rate constants could be grouped into four statistically distinct
      clusters reflecting the core structural features of model DOM precursors (i.e.,
      non-beta-diketone aliphatics, beta-diketone aliphatics, non-beta-diketone
      phenolics, and beta-diketone phenolics). A comparative approach built upon
      hierarchical cluster analysis was developed to gain further insight into the
      chlorine reactivity patterns of HAA precursors in inland lake waters as defined
      by the relative proximity to four model precursor clusters. This work highlights
      the potential for implementing an integrated kinetic-clustering approach to
      constrain the chlorine reactivity of DOM in source waters. 

PMID- 24299069
TI  - On the value and pitfalls of follow-up biopsies after acute rejection.

PMID- 24299070
TI  - Demonstration of a Ge/GeSn/Ge quantum-well microdisk resonator on silicon:
      enabling high-quality Ge(Sn) materials for micro- and nanophotonics.
AB  - We theoretically study and experimentally demonstrate a pseudomorphic
      Ge/Ge0.92Sn0.08/Ge quantum-well microdisk resonator on Ge/Si (001) as a route
      toward a compact GeSn-based laser on silicon. The structure theoretically
      exhibits many electronic and optical advantages in laser design, and microdisk
      resonators using these structures can be precisely fabricated away from highly
      defective regions in the Ge buffer using a novel etch-stop process.
      Photoluminescence measurements on 2.7 MUm diameter microdisks reveal sharp
      whispering-gallery-mode resonances (Q > 340) with strong luminescence. 

PMID- 24299071
TI  - Investigation of MCPA (4-Chloro-2-ethylphenoxyacetate) resistance in wild radish
      (Raphanus raphanistrum L.).
AB  - The phenoxy herbicides (e.g., 2,4-D and MCPA) are used widely in agriculture for
      the selective control of broadleaf weeds. In Western Australia, the reliance on
      phenoxy herbicides has resulted in the widespread evolution of phenoxy resistance
      in wild radish (Raphanus raphanistrum) populations. In this research the
      inheritance and mechanism of MCPA resistance in wild radish were determined.
      Following classical breeding procedures, F1, F2, and backcross progeny were
      generated. The F1 progeny showed an intermediate response to MCPA, compared to
      parents, suggesting that MCPA resistance in wild radish is inherited as an
      incompletely dominant trait. Segregation ratios observed in F2 (3:1;
      resistant:susceptible) and backcross progeny (1:1; resistant to susceptible)
      indicated that the MCPA resistance is controlled by a single gene in wild radish.
      Radiolabeled MCPA studies suggested no difference in MCPA uptake or metabolism
      between resistant and susceptible wild radish; however, resistant plants rapidly
      translocated more (14)C-MCPA to roots than susceptible plants, which may have
      been exuded from the plant. Understanding the genetic basis and mechanism of
      phenoxy resistance in wild radish will help formulate prudent weed management
      strategies to reduce the incidence of phenoxy resistance. 

PMID- 24299072
TI  - Documentation of atrial fibrillation prior to first-ever ischemic stroke.
AB  - OBJECTIVES: We assessed the prevalence of atrial fibrillation (AF) prior to first
      ever ischemic stroke by examining a comprehensive electronic ECG archive.
      METHODS: The study sample comprised 336 consecutive stroke patients (median age
      76 (IQ16) y, 200 men) enrolled in Lund Stroke Register from March 2001 to
      February 2002 and 336 age- and gender-matched controls without stroke history. AF
      prior to admission was studied using the regional electronic ECG database and
      record linkage with the National Swedish Hospital Discharge Register (SHDR).
      Medical records were reviewed for AF documentation and CHA2 DS2-VASc risk score.
      RESULTS: Atrial fibrillation before or at stroke onset was detected in 109
      (32.4%) stroke patients and 44 (13.1%) controls, P<0.001. Twenty-five of 109
      stroke patients had AF detected only on previous ECG (n=14) or through the SHDR
      (n=11). The most prevalent type of AF in stroke group was non-permanent AF
      (59.6%). AF prevalence among patients admitted with sinus rhythm at hospital
      admission (n=266) was higher in those with CHA2 DS2 -VASc score>=6 (28.6%) than
      with CHA2 DS2-VASc score<6 (13.0%), P=0.043. CONCLUSION: Comprehensive approach
      for AF screening allows detecting AF in one-third of patients admitted with first
      ever ischemic stroke. Patients with high cardiovascular risk are more likely to
      have non-permanent AF.

PMID- 24299073
TI  - Realization of metal-insulator transition and oxidation in silver nanowire
      percolating networks by terahertz reflection spectroscopy.
AB  - Metal nanowires (NWs) enable versatile applications in printed electronics and
      optoelectronics by serving as thin and flexible transparent electrodes. The
      performance of metal NWs as thin electrodes is highly correlated to the
      connectivity of NW meshes. The percolation threshold of metal NW films
      corresponds to the minimum density of NWs to form the transparent, yet conductive
      metal NW networks. Here, we determine the percolation threshold of silver NW
      (AgNW) networks by using morphological analysis and terahertz (THz) reflection
      spectroscopy. From the divergent behavior of carrier scattering time and the
      increase of carrier backscattering factor, the critical NW density at which
      crossover from Drude to non-Drude behavior of THz conductivity occurs can be
      unambiguously determined for AgNW thin films. Furthermore, the natural oxidation
      of AgNWs which causes the gradual reduction of the connectivity of the AgNW
      network is also realized by the THz spectroscopy. The selective oxidation of NW
      to-NW junctions weakens the ohmic contact, and for AgNWs near a critical density,
      it can even lead to metal-insulator transition. The presented results offer
      invaluable information to accelerate the deployment of metal nanowires for next
      generation electronics and optoelectronics on flexible substrates. 

PMID- 24299074
TI  - Multiple host-cell recombination pathways act in Agrobacterium-mediated
      transformation of plant cells.
AB  - Using floral-dip, tumorigenesis and root callus transformation assays of both
      germline and somatic cells, we present here results implicating the four major
      non-homologous and homologous recombination pathways in Agrobacterium-mediated
      transformation of Arabidopsis thaliana. All four single mutant lines showed
      similar mild reductions in transformability, but knocking out three of four
      pathways severely compromised Agrobacterium-mediated transformation. Although
      integration of T-DNA into the plant genome is severely compromised in the absence
      of known DNA double-strand break repair pathways, it does still occur, suggesting
      the existence of other pathways involved in T-DNA integration. Our results
      highlight the functional redundancy of the four major plant recombination
      pathways in transformation, and provide an explanation for the lack of strong
      effects observed in previous studies on the roles of plant recombination
      functions in transformation. 

PMID- 24299075
TI  - Are implicit self-esteem measures valid for assessing individual and cultural
      differences?
AB  - OBJECTIVE: Our research utilized two popular theoretical conceptualizations of
      implicit self-esteem: 1) implicit self-esteem as a global automatic reaction to
      the self; and 2) implicit self-esteem as a context/domain specific construct.
      Under this framework, we present an extensive search for implicit self-esteem
      measure validity among different cultural groups (Study 1) and under several
      experimental manipulations (Study 2). METHOD: In Study 1, Euro-Canadians (N =
      107), Asian-Canadians (N = 187), and Japanese (N = 112) completed a battery of
      implicit self-esteem, explicit self-esteem, and criterion measures. Included
      implicit self-esteem measures were either popular or provided methodological
      improvements upon older methods. Criterion measures were sampled from previous
      research on implicit self-esteem and included self-report and independent
      ratings. In Study 2, Americans (N = 582) completed a shorter battery of these
      same types of measures under either a control condition, an explicit prime meant
      to activate the self-concept in a particular context, or prime meant to activate
      self-competence related implicit attitudes. RESULTS: Across both studies,
      explicit self-esteem measures far outperformed implicit self-esteem measures in
      all cultural groups and under all experimental manipulations. CONCLUSION:
      Implicit self-esteem measures are not valid for individual or cross-cultural
      comparisons. We speculate that individuals may not form implicit associations
      with the self as an attitudinal object.

PMID- 24299077
TI  - Continental-scale governance and the hastening of loss of Australia's
      biodiversity.

PMID- 24299061
TI  - Combinatorial peptide libraries: mining for cell-binding peptides.

PMID- 24299079
TI  - Introduction.

PMID- 24299076
TI  - Relative resistance of HIV-1 founder viruses to control by interferon-alpha.
AB  - BACKGROUND: Following mucosal human immunodeficiency virus type 1 (HIV-1)
      transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial
      virus replication in the mucosa and draining lymph nodes. However, the role
      played by IFN-stimulated antiviral activity in restricting HIV-1 replication
      during the initial stages of infection is not clear. We hypothesized that if type
      1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of
      infection, the founder viruses that succeed in establishing systemic infection
      would be more IFN-resistant than viruses replicating during chronic infection,
      when type 1 IFNs are produced at much lower levels. To address this hypothesis,
      the relative resistance of virus isolates derived from HIV-1-infected individuals
      during acute and chronic infection to control by type 1 IFNs was analysed.
      RESULTS: The replication of plasma virus isolates generated from subjects acutely
      infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced
      but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for
      IFNalpha2 (22 U/ml) was lower than that for IFNbeta (346 U/ml), although at
      maximally-inhibitory concentrations both IFN subtypes inhibited virus replication
      to similar extents. Individual virus isolates exhibited differential
      susceptibility to inhibition by IFNalpha2 and IFNbeta, likely reflecting
      variation in resistance to differentially up-regulated IFN-stimulated genes.
      Virus isolates from subjects acutely infected with HIV-1 were significantly more
      resistant to in vitro control by IFNalpha than virus isolates generated from the
      same individuals during chronic, asymptomatic infection. Viral IFN resistance
      declined rapidly after the acute phase of infection: in five subjects, viruses
      derived from six-month consensus molecular clones were significantly more
      sensitive to the antiviral effects of IFNs than the corresponding founder
      viruses. CONCLUSIONS: The establishment of systemic HIV-1 infection by relatively
      IFNalpha-resistant founder viruses lends strong support to the hypothesis that
      IFNalpha plays an important role in the control of HIV-1 replication during the
      earliest stages of infection, prior to systemic viral spread. These findings
      suggest that it may be possible to harness the antiviral activity of type 1 IFNs
      in prophylactic and potentially also therapeutic strategies to combat HIV-1
      infection.

PMID- 24299080
TI  - Climate change, marine environments, and the US Endangered species act.
AB  - Climate change is expected to be a top driver of global biodiversity loss in the
      21st century. It poses new challenges to conserving and managing imperiled
      species, particularly in marine and estuarine ecosystems. The use of climate
      related science in statutorily driven species management, such as under the U.S.
      Endangered Species Act (ESA), is in its early stages. This article provides an
      overview of ESA processes, with emphasis on the mandate to the National Marine
      Fisheries Service (NMFS) to manage listed marine, estuarine, and anadromous
      species. Although the ESA is specific to the United States, its requirements are
      broadly relevant to conservation planning. Under the ESA, species, subspecies,
      and "distinct population segments" may be listed as either endangered or
      threatened, and taking of most listed species (harassing, harming, pursuing,
      wounding, killing, or capturing) is prohibited unless specifically authorized via
      a case-by-case permit process. Government agencies, in addition to avoiding take,
      must ensure that actions they fund, authorize, or conduct are not likely to
      jeopardize a listed species' continued existence or adversely affect designated
      critical habitat. Decisions for which climate change is likely to be a key factor
      include: determining whether a species should be listed under the ESA,
      designating critical habitat areas, developing species recovery plans, and
      predicting whether effects of proposed human activities will be compatible with
      ESA-listed species' survival and recovery. Scientific analyses that underlie
      these critical conservation decisions include risk assessment, long-term recovery
      planning, defining environmental baselines, predicting distribution, and defining
      appropriate temporal and spatial scales. Although specific guidance is still
      evolving, it is clear that the unprecedented changes in global ecosystems brought
      about by climate change necessitate new information and approaches to
      conservation of imperiled species. El Cambio Climatico, los Ecosistemas Marinos y
      el Acta Estadunidense de Especies en Peligro. 

PMID- 24299081
TI  - Choosing and using climate-change scenarios for ecological-impact assessments and
      conservation decisions.
AB  - Increased concern over climate change is demonstrated by the many efforts to
      assess climate effects and develop adaptation strategies. Scientists, resource
      managers, and decision makers are increasingly expected to use climate
      information, but they struggle with its uncertainty. With the current
      proliferation of climate simulations and downscaling methods, scientifically
      credible strategies for selecting a subset for analysis and decision making are
      needed. Drawing on a rich literature in climate science and impact assessment and
      on experience working with natural resource scientists and decision makers, we
      devised guidelines for choosing climate-change scenarios for ecological impact
      assessment that recognize irreducible uncertainty in climate projections and
      address common misconceptions about this uncertainty. This approach involves
      identifying primary local climate drivers by climate sensitivity of the
      biological system of interest; determining appropriate sources of information for
      future changes in those drivers; considering how well processes controlling local
      climate are spatially resolved; and selecting scenarios based on considering
      observed emission trends, relative importance of natural climate variability, and
      risk tolerance and time horizon of the associated decision. The most appropriate
      scenarios for a particular analysis will not necessarily be the most appropriate
      for another due to differences in local climate drivers, biophysical linkages to
      climate, decision characteristics, and how well a model simulates the climate
      parameters and processes of interest. Given these complexities, we recommend
      interaction among climate scientists, natural and physical scientists, and
      decision makers throughout the process of choosing and using climate-change
      scenarios for ecological impact assessment. Seleccion y Uso de Escenarios de
      Cambio Climatico para Estudios de Impacto Ecologico y Decisiones de Conservacion.

PMID- 24299082
TI  - Floodplain rehabilitation as a hedge against hydroclimatic uncertainty in a
      migration corridor of threatened steelhead.
AB  - A strategy for recovering endangered species during climate change is to restore
      ecosystem processes that moderate effects of climate shifts. In mid-latitudes,
      storm patterns may shift their intensity, duration, and frequency. These shifts
      threaten flooding in human communities and reduce migration windows (conditions
      suitable for migration after a storm) for fish. Rehabilitation of historic
      floodplains can in principle reduce these threats via transient storage of storm
      water, but no one has quantified the benefit of floodplain rehabilitation for
      migrating fish, a widespread biota with conservation and economic value. We used
      simple models to quantify migration opportunity for a threatened migratory fish,
      steelhead (Oncorhynchus mykiss), in an episodic rain-fed river system, the Pajaro
      River in central California. We combined flow models, bioenergetic models, and
      existing climate projections to estimate the sensitivity of migration windows to
      altered storm patterns under alternate scenarios of floodplain rehabilitation.
      Generally, migration opportunities were insensitive to warming, weakly sensitive
      to duration or intensity of storms, and proportionately sensitive to frequency of
      storms. The rehabilitation strategy expanded migration windows by 16-28%
      regardless of climate outcomes. Warmer conditions raised the energy cost of
      migrating, but not enough to matter biologically. Novel findings were that fewer
      storms appeared to pose a bigger threat to migrating steelhead than warmer or
      smaller storms and that floodplain rehabilitation lessened the risk from fewer or
      smaller storms across all plausible hydroclimatic outcomes. It follows that
      statistical downscaling methods may mischaracterize risk, depending on how they
      resolve overall precipitation shifts into changes of storm frequency as opposed
      to storm size. Moreover, anticipating effects of climate shifts that are
      irreducibly uncertain (here, rainfall) may be more important than anticipating
      effects of relatively predictable changes such as warming. This highlights a need
      to credibly identify strategies of ecosystem rehabilitation that are robust to
      uncertainty. Rehabilitacion de Planicies Inundables como Cerco contra la
      Incertidumbre Hidroclimatica en un Corredor Migratorio de Oncorhynchus mykiss,
      Especie Amenazada. 

PMID- 24299083
TI  - Incorporating climate and ocean change into extinction risk assessments for 82
      coral species.
AB  - Many marine invertebrate species facing potential extinction have uncertain
      taxonomies and poorly known demographic and ecological traits. Uncertainties are
      compounded when potential extinction drivers are climate and ocean changes whose
      effects on even widespread and abundant species are only partially understood.
      The U.S. Endangered Species Act mandates conservation management decisions
      founded on the extinction risk to species based on the best available science at
      the time of consideration-requiring prompt action rather than awaiting better
      information. We developed an expert-opinion threat-based approach that entails a
      structured voting system to assess extinction risk from climate and ocean changes
      and other threats to 82 coral species for which population status and threat
      response information was limited. Such methods are urgently needed because
      constrained budgets and manpower will continue to hinder the availability of
      desired data for many potentially vulnerable marine species. Significant species
      specific information gaps and uncertainties precluded quantitative assessments of
      habitat loss or population declines and necessitated increased reliance on
      demographic characteristics and threat vulnerabilities at genus or family levels.
      Adapting some methods (e.g., a structured voting system) used during other
      assessments and developing some new approaches (e.g., integrated assessment of
      threats and demographic characteristics), we rated the importance of threats
      contributing to coral extinction risk and assessed those threats against
      population status and trend information to evaluate each species' extinction risk
      over the 21st century. This qualitative assessment resulted in a ranking with an
      uncertainty range for each species according to their estimated likelihood of
      extinction. We offer guidance on approaches for future biological extinction risk
      assessments, especially in cases of data-limited species likely to be affected by
      global-scale threats. Incorporacion del Cambio Climatico y Oceanico en Estudios
      de Riesgo de Extincion para 82 Especies de Coral. 

PMID- 24299084
TI  - Interactive effects of water diversion and climate change for juvenile chinook
      salmon in the lemhi river basin (USA.).
AB  - The combined effects of water diversion and climate change are a major
      conservation challenge for freshwater ecosystems. In the Lemhi Basin, Idaho
      (U.S.A.), water diversion causes changes in streamflow, and climate change will
      further affect streamflow and temperature. Shifts in streamflow and temperature
      regimes can affect juvenile salmon growth, movement, and survival. We examined
      the potential effects of water diversion and climate change on juvenile Chinook
      salmon (Oncorhynchus tshawytscha), a species listed as threatened under the U.S.
      Endangered Species Act (ESA). To examine the effects for juvenile survival, we
      created a model relating 19 years of juvenile survival data to streamflow and
      temperature and found spring streamflow and summer temperature were good
      predictors of juvenile survival. We used these models to project juvenile
      survival for 15 diversion and climate-change scenarios. Projected survival was 42
      58% lower when streamflows were diverted than when streamflows were undiverted.
      For diverted streamflows, 2040 climate-change scenarios (ECHO-G and CGCM3.1 T47)
      resulted in an additional 11-39% decrease in survival. We also created models
      relating habitat carrying capacity to streamflow and made projections for
      diversion and climate-change scenarios. Habitat carrying capacity estimated for
      diverted streamflows was 17-58% lower than for undiverted streamflows. Climate
      change scenarios resulted in additional decreases in carrying capacity for the
      dry (ECHO-G) climate model. Our results indicate climate change will likely pose
      an additional stressor that should be considered when evaluating the effects of
      anthropogenic actions on salmon population status. Thus, this type of analysis
      will be especially important for evaluating effects of specific actions on a
      particular species. Efectos Interactivos de la Desviacion del Agua y el Cambio
      Climatico en Individuos Juveniles de Salmon Chinook en la Cuenca del Rio Lemhi
      (E.U.A.). 

PMID- 24299085
TI  - Estimating effects of tidal power projects and climate change on threatened and
      endangered marine species and their food web.
AB  - Marine hydrokinetic power projects will operate as marine environments change in
      response to increased atmospheric carbon dioxide concentrations. We considered
      how tidal power development and stressors resulting from climate change may
      affect Puget Sound species listed under the U.S. Endangered Species Act (ESA) and
      their food web. We used risk tables to assess the singular and combined effects
      of tidal power development and climate change. Tidal power development and
      climate change posed risks to ESA-listed species, and risk increased with
      incorporation of the effects of these stressors on predators and prey of ESA
      listed species. In contrast, results of a model of strikes on ESA-listed species
      from turbine blades suggested that few ESA-listed species are likely to be killed
      by a commercial-scale tidal turbine array. We applied scenarios to a food web
      model of Puget Sound to explore the effects of tidal power and climate change on
      ESA-listed species using more quantitative analytical techniques. To simulate
      development of tidal power, we applied results of the blade strike model. To
      simulate environmental changes over the next 50 years, we applied scenarios of
      change in primary production, plankton community structure, dissolved oxygen,
      ocean acidification, and freshwater flooding events. No effects of tidal power
      development on ESA-listed species were detected from the food web model output,
      but the effects of climate change on them and other members of the food web were
      large. Our analyses exemplify how natural resource managers might assess
      environmental effects of marine technologies in ways that explicitly incorporate
      climate change and consider multiple ESA-listed species in the context of their
      ecological community. Estimacion de los Efectos de Proyectos de Energia de las
      Mareas y el Cambio Climatico sobre Especies Marinas Amenazadas y en Peligro y su
      Red Alimentaria. 

PMID- 24299086
TI  - Combined effects of climate change and bank stabilization on shallow water
      habitats of chinook salmon.
AB  - Significant challenges remain in the ability to estimate habitat change under the
      combined effects of natural variability, climate change, and human activity. We
      examined anticipated effects on shallow water over low-sloped beaches to these
      combined effects in the lower Willamette River, Oregon, an area highly altered by
      development. A proposal to stabilize some shoreline with large rocks (riprap)
      would alter shallow water areas, an important habitat for threatened Chinook
      salmon (Oncorhynchus tshawytscha), and would be subject to U.S. Endangered
      Species Act-mandated oversight. In the mainstem, subyearling Chinook salmon
      appear to preferentially occupy these areas, which fluctuate with river stages.
      We estimated effects with a geospatial model and projections of future river
      flows. Recent (1999-2009) median river stages during peak subyearling occupancy
      (April-June) maximized beach shallow water area in the lower mainstem. Upstream
      shallow water area was maximized at lower river stages than have occurred
      recently. Higher river stages in April-June, resulting from increased flows
      predicted for the 2080s, decreased beach shallow water area 17-32%. On the basis
      of projected 2080s flows, more than 15% of beach shallow water area was displaced
      by the riprap. Beach shallow water area lost to riprap represented up to 1.6% of
      the total from the mouth to 12.9 km upstream. Reductions in shallow water area
      could restrict salmon feeding, resting, and refuge from predators and potentially
      reduce opportunities for the expression of the full range of life-history
      strategies. Although climate change analyses provided useful information,
      detailed analyses are prohibitive at the project scale for the multitude of small
      projects reviewed annually. The benefits of our approach to resource managers
      include a wider geographic context for reviewing similar small projects in
      concert with climate change, an approach to analyze cumulative effects of similar
      actions, and estimation of the actions' long-term effects. Efectos Combinados del
      Cambio Climatico y la Estabilizacion de Bordes de Rios Habitats de Aguas Poco
      Profundas del Salmon Chinook. 

PMID- 24299087
TI  - Structuring decisions for managing threatened and endangered species in a
      changing climate.
AB  - The management of endangered species under climate change is a challenging and
      often controversial task that incorporates input from a variety of different
      environmental, economic, social, and political interests. Yet many listing and
      recovery decisions for endangered species unfold on an ad hoc basis without
      reference to decision-aiding approaches that can improve the quality of
      management choices. Unlike many treatments of this issue, which consider
      endangered species management a science-based problem, we suggest that a clear
      decision-making process is equally necessary. In the face of new threats due to
      climate change, managers' choices about endangered species require closely linked
      analyses and deliberations that identify key objectives and develop measurable
      attributes, generate and compare management alternatives, estimate expected
      consequences and key sources of uncertainty, and clarify trade-offs across
      different dimensions of value. Several recent cases of endangered species
      conservation decisions illustrate our proposed decision-focused approach,
      including Gulf of Maine Atlantic salmon (Salmo salar) recovery framework
      development, Cultus Lake sockeye salmon (Oncorhynchus nerka) management, and
      Upper Columbia River white sturgeon (Acipenser transmontanus) recovery planning.
      Estructuracion de Decisiones para Manejar Especies Amenazadas y en Peligro en un
      Clima Cambiante. 

PMID- 24299088
TI  - Incorporating climate science in applications of the US endangered species act
      for aquatic species.
AB  - Aquatic species are threatened by climate change but have received comparatively
      less attention than terrestrial species. We gleaned key strategies for scientists
      and managers seeking to address climate change in aquatic conservation planning
      from the literature and existing knowledge. We address 3 categories of
      conservation effort that rely on scientific analysis and have particular
      application under the U.S. Endangered Species Act (ESA): assessment of overall
      risk to a species; long-term recovery planning; and evaluation of effects of
      specific actions or perturbations. Fewer data are available for aquatic species
      to support these analyses, and climate effects on aquatic systems are poorly
      characterized. Thus, we recommend scientists conducting analyses supporting ESA
      decisions develop a conceptual model that links climate, habitat, ecosystem, and
      species response to changing conditions and use this model to organize analyses
      and future research. We recommend that current climate conditions are not
      appropriate for projections used in ESA analyses and that long-term projections
      of climate-change effects provide temporal context as a species-wide assessment
      provides spatial context. In these projections, climate change should not be
      discounted solely because the magnitude of projected change at a particular time
      is uncertain when directionality of climate change is clear. Identifying likely
      future habitat at the species scale will indicate key refuges and potential range
      shifts. However, the risks and benefits associated with errors in modeling future
      habitat are not equivalent. The ESA offers mechanisms for increasing the overall
      resilience and resistance of species to climate changes, including establishing
      recovery goals requiring increased genetic and phenotypic diversity, specifying
      critical habitat in areas not currently occupied but likely to become important,
      and using adaptive management. Incorporacion de las Ciencias Climaticas en las
      Aplicaciones del Acta Estadunidense de Especies en Peligro para Especies
      Acuaticas. 

PMID- 24299090
TI  - Spotlight on sibling involvement in schizophrenia treatment.
AB  - OBJECTIVE: The purpose of this paper is to explore a literature gap--sibling
      involvement in the care and support of people with schizophrenia, and to make
      recommendations for filling the gap. METHOD: The method used was observation and
      documentation of clinical notes over a ten-year period in an outpatient clinic
      for women with schizophrenia. Illustrative examples were selected from
      approximately 200 entries dealing with sibling relationships. FINDINGS: Siblings
      constitute an important segment of the social network of persons with
      schizophrenia, although they do not usually take an active part in their brother
      or sister's care until parents are no longer able to cope alone. The role of
      primary caregiver appears to be a stressful one for siblings. The closest sibling
      bonds were those between sisters, and in most cases, the eldest girl in the
      family assumed the caregiver role. This depended, however, on the family's means,
      values, and cultural traditions, as well as on the personal attributes and life
      circumstances of the siblings. Financial, human, and social capital were critical
      determinants of sibling involvement. Sharing responsibilities and negotiating the
      distribution of required caretaking tasks was often the most effective way of
      dealing with the burden of care giving. CONCLUSION: Although some clinical
      recommendations can be made, specificities that distinguish this population and
      the effectiveness of sibling caregiving need to be further researched.

PMID- 24299091
TI  - The functional implications of motor, cognitive, psychiatric, and social problem
      solving states in Huntington's disease.
AB  - OBJECTIVE: Huntington's disease (HD) is a genetic, neurodegenerative disorder
      characterized by motor, cognitive, and psychiatric dysfunction. In HD, the
      inability to solve problems successfully affects not only disease coping, but
      also interpersonal relationships, judgment, and independent living. The aim of
      the present study was to examine social problem-solving (SPS) in well
      characterized HD and at-risk (AR) individuals and to examine its unique and
      conjoint effects with motor, cognitive, and psychiatric states on functional
      ratings. METHOD: Sixty-three participants, 31 HD and 32 gene-positive AR, were
      included in the study. Participants completed the Social Problem-Solving
      Inventory-Revised: Long (SPSI-R:L), a 52-item, reliable, standardized measure of
      SPS. Items are aggregated under five scales (Positive, Negative, and Rational
      Problem-Solving; Impulsivity/Carelessness and Avoidance Styles). Participants
      also completed the Unified Huntington's Disease Rating Scale functional,
      behavioral, and cognitive assessments, as well as additional neuropsychological
      examinations and the Symptom Checklist-90-Revised (SCL-90R). A structural
      equation model was used to examine the effects of motor, cognitive, psychiatric,
      and SPS states on functionality. RESULTS: The multifactor structural model fit
      well descriptively. Cognitive and motor states uniquely and significantly
      predicted function in HD; however, neither psychiatric nor SPS states did. SPS
      was, however, significantly related to motor, cognitive, and psychiatric states,
      suggesting that it may bridge the correlative gap between psychiatric and
      cognitive states in HD. CONCLUSION: SPS may be worth assessing in conjunction
      with the standard gamut of clinical assessments in HD. Suggestions for future
      research and implications for patients, families, caregivers, and clinicians are
      discussed.

PMID- 24299092
TI  - Use of evidence-based treatment for posttraumatic stress disorder in Army
      behavioral healthcare.
AB  - OBJECTIVE: To identify the extent to which evidence-based psychotherapy (EBP) and
      psychopharmacologic treatments for posttraumatic stress disorder (PTSD) are
      provided to U.S. service members in routine practice, and the degree to which
      they are consistent with evidence-based treatment guidelines. METHOD: We surveyed
      the majority of Army behavioral health providers (n = 2,310); surveys were
      obtained from 543 (26%). These clinicians reported clinical data on a total
      sample of 399 service member patients. Of these patients, 110 (28%) had a
      reported PTSD diagnosis. Data were weighted to account for sampling design and
      nonresponses. RESULTS: Army providers reported 86% of patients with PTSD received
      evidence-based psychotherapy (EBP) for PTSD. As formal training hours in EBPs
      increased, reported use of EBPs significantly increased. Although EBPs for PTSD
      were reported to be widely used, clinicians who deliver EBP frequently reported
      not adhering to all core procedures recommended in treatment manuals; less than
      half reported using all the manualized core EBP techniques. CONCLUSIONS: Further
      research is necessary to understand why clinicians modify EBP treatments, and
      what impact this has on treatment outcomes. More data regarding the implications
      for treatment effectiveness and the role of clinical context, patient
      preferences, and clinical decision-making in adapting EBPs could help inform
      training efforts and the ways that these treatments may be better adapted for the
      military.

PMID- 24299093
TI  - Male imprisoned firesetters have different characteristics than other imprisoned
      offenders and require specialist treatment.
AB  - OBJECTIVE: This study investigated whether a group of firesetters (n = 68) could
      be distinguished, psychologically, from a matched group of non-firesetting
      offenders (n = 68). METHOD: Participants completed measures examining
      psychological variables relating to fire, emotional/self-regulation, social
      competency, self-concept, boredom proneness, and impression management. Official
      prison records were also examined to record offending history and other offense
      related variables. A series of MANOVAs were conducted with conceptually related
      measures identified as the dependent variables. Follow-up discriminant function
      and clinical cut-off score analyses were also conducted to examine the best
      discriminating variables for firesetters. RESULTS: Firesetters were clearly
      distinguishable, statistically, from non-firesetters on three groups of
      conceptually related measures relating to: fire, emotional/self-regulation, and
      self-concept. The most successful variables for the discrimination of firesetters
      determined via statistical and clinical significance testing were higher levels
      of anger-related cognition, interest in serious fires, and identification with
      fire and lower levels of perceived fire safety awareness, general self-esteem,
      and external locus of control. CONCLUSIONS: Firesetters appear to be a specialist
      group of offenders who hold unique psychological characteristics. Firesetters are
      likely to require specialist treatment to target these psychological needs as
      opposed to generic offending behavior programs.

PMID- 24299094
TI  - Borderline personality disorder, exposure to interpersonal trauma, and
      psychiatric comorbidity in urban primary care patients.
AB  - OBJECTIVE: Few data are available on interpersonal trauma as a risk factor for
      borderline personality disorder (BPD) and its psychiatric comorbidity in ethnic
      minority primary care populations. This study aimed to examine the relation
      between trauma exposure and BPD in low-income, predominantly Hispanic primary
      care patients. METHOD: Logistic regression was used to analyze data from
      structured clinical interviews and self-report measures (n = 474). BPD was
      assessed with the McLean screening scale. Trauma exposure was assessed with the
      Life Events Checklist (LEC); posttraumatic stress disorder (PTSD) was assessed
      with the Lifetime Composite International Diagnostic Interview, other psychiatric
      disorders with the SCID-I, and functional impairment with items from the Sheehan
      Disability Scale and Social Adjustment Scale Self-Report (SAS-SR). RESULTS: Of
      the 57 (14%) patients screening positive for BPD, 83% reported a history of
      interpersonally traumatic events such as sexual and physical assault or abuse.
      While interpersonal trauma experienced during adulthood was as strongly
      associated with BPD as interpersonal trauma experienced during childhood,
      noninterpersonal trauma was associated with BPD only if it had occurred during
      childhood. The majority (91%) of patients screening positive for BPD met criteria
      for at least one current DSM-IV Axis I diagnosis and exhibited significant levels
      of functional impairment. CONCLUSION: Increased awareness of BPD in minority
      patients attending primary care clinics, high rates of exposure to interpersonal
      trauma, and elevated risk for psychiatric comorbidity in this population may
      enhance physicians' understanding, treatment, and referral of BPD patients.

PMID- 24299095
TI  - Pathological narcissism and acute anxiety symptoms after trauma: a study of
      Israeli civilians exposed to war.
AB  - OBJECTIVE: Diathesis-stress models of posttraumatic stress disorder (PTSD)
      hypothesize that exposure to trauma may interact with individual differences in
      the development of PTSD. Previous studies have not assessed immediate responses
      to a proximate stressor, but the current "natural laboratory" study was designed
      to empirically test the role that individual differences in pathological
      narcissism may play in the development of acute anxiety symptoms among civilians
      facing rocket and missile fire. METHOD: We assessed demographic features, trauma
      exposure severity, narcissistic personality features, and acute anxiety symptoms
      (PTSD and General Anxiety Disorder [GAD]) among 342 Israeli female adults during
      the November 2012 eruption of violence in the Middle East. RESULTS: Results
      demonstrate an association between exposure severity and acute anxiety symptoms
      (both PTSD and GAD) for individuals with high levels of pathological narcissism
      but not for those with low levels of pathological narcissism. These results
      suggest that individuals with narcissistic personality features are at high risk
      for the development of acute anxiety symptoms following exposure to
      uncontrollable and life-threatening mass trauma. CONCLUSION: The findings
      underscore the role of intra-personal resources in the immediate psychological
      aftermath of war by highlighting the increased risk associated with narcissistic
      personality features. Theoretical and clinical implications of the findings are
      discussed.

PMID- 24299099
TI  - Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected
      by severity, but not age.
AB  - Duration of viral shedding following infection is an important determinant of
      disease transmission, informing both control policies and disease modelling. We
      undertook a systematic literature review of the duration of influenza
      A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness
      and receipt of antiviral treatment. Studies were identified by searching the
      PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and
      'shedding'. Any study of humans with an outcome measure of viral shedding was
      eligible for inclusion in the review. Comparisons by age, degree of severity and
      antiviral treatment were made with forest plots. The search returned 214 articles
      of which 22 were eligible for the review. Significant statistical heterogeneity
      between studies precluded meta-analysis. The mean duration of viral shedding
      generally increased with severity of clinical presentation, but we found no
      evidence of longer shedding duration of influenza A(H1N1)pdm09 among children
      compared with adults. Shorter viral shedding duration was observed when
      oseltamivir treatment was administered within 48 hours of illness onset.
      Considerable differences in the design and analysis of viral shedding studies
      limit their comparison and highlight the need for a standardised approach. These
      insights have implications not only for pandemic planning, but also for informing
      responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has
      become established as the seasonal H1N1 influenza virus. 

PMID- 24299100
TI  - Sucralfate paste enema: a new method of topical treatment for haemorrhagic
      radiation proctitis.
AB  - AIM: Rectal sucralfate has been reported to deliver clinical improvement in
      haemorrhagic radiation proctitis, but patients with active proctitis find the
      enema suspension difficult to retain thus reducing compliance and effectiveness.
      We describe a novel method of rectal administration via a low-volume sucralfate
      paste and report its results in a series of 23 patients. METHOD: Patients with
      rectal bleeding occurring more than 6 months after radiotherapy were shown how to
      prepare and self-administer sucralfate paste enemas (SPEs) twice daily for 6
      weeks. The SPE was prepared using two sucralfate 1-g tablets mixed with 4.5 ml of
      water in an enema applicator producing a low-volume paste. The clinical response
      was evaluated by comparison of pre- and posttreatment clinical proctitis scores
      (Radiation Therapy Oncology Group/European Organisation for Research and
      Treatment of Cancer). RESULTS: Eighteen male (postprostatic radiotherapy) and
      five female (postcervical radiotherapy) patients with a median age of 67 (32-75)
      years were included. The median interval between pelvic irradiation and SPE
      treatment was 24 (7-69) months. Twenty-two patients had full clinical scoring, of
      whom 16 (73%) demonstrated clinical improvement. Six (27%) had neither clinical
      improvement nor deterioration. Seven (32%) had resolution of all symptoms.
      CONCLUSION: Most patients demonstrated clinical improvement. This initial
      experience of the sucralfate paste enema may provide the basis for a prospective
      study of its effectiveness in the treatment of haemorrhagic radiation proctitis.

PMID- 24299101
TI  - Decision-to-delivery interval in suspected placental abruption - association with
      pregnancy outcome.
AB  - OBJECTIVE: To determine the association between decision to delivery interval
      (DDI) and short-term perinatal outcome in cases of suspected placental abruption
      delivered by cesarean section (CS). STUDY DESIGN: A retrospective cohort study of
      all cases of placental abruption delivered by CS (2010-2012) in a single
      university affiliated tertiary center. Composite adverse neonatal and maternal
      outcome were assessed. RESULTS: The rate of placental abruption was 0.5% (140/27
      677 deliveries) and 65/140 (46%) were delivered by CS. Indications for CS were
      non-reassuring fetal heart rate (NRFHR) in 32/65 (49.3%), maternal bleeding 20/65
      (30.7%) and other indications in 13/65 (20%). Obstetrical and labor
      characteristics were similar unrelated to the indication for CS. Gestational age
      at delivery was higher in the group operated due to NRFHR (36 +/- 4.3, 34 +/- 3.7
      and 32 +/- 4.1 weeks, respectively, p = 0.03). DDI was shortest when CS was due
      to NRFHR followed by CS due to maternal bleeding or other indications (23 +/- 19,
      30 +/- 16, 50 +/- 40 min, respectively, p = 0.001). The umbilical artery PH was
      lower in those who operated due to NRFHR (7.17 +/- 0.17, 7.23 +/- 0.06 and 7.30
      +/- 0.09, respectively, p = 0.002). The overall rate of neonatal and maternal
      composite outcome was 66% and 40%, respectively with no significant difference in
      relation to indication for CS. CONCLUSION: In cases of suspected placental
      abruption, fetal short-term morbidity is probably related to the indication for
      CS and not only to DDI.

PMID- 24299102
TI  - Measurement of the difference in intraocular pressure between the sitting and
      lying body positions in healthy subjects: direct comparison of the Icare Pro with
      the Goldmann applanation tonometer, Pneumatonometer and Tonopen XL.
AB  - BACKGROUND: Change in intraocular pressure is known to occur with body posture.
      Previously, markedly different estimations of this change were reported. The
      Icare Pro (Icare; Tiolat Oy, Helsinki, Finland) is designed to measure
      intraocular pressure with the subject supine. We compared the measurement of
      postural change in intraocular pressure obtained with this and 3 other
      tonometers: Goldmann applanation tonometer (CSO, Firenze, Italy), Pneumatonometer
      (Model 30, Reichert, Depew, NY, USA) and the Tonopen XL (Reichert). DESIGN:
      Prospective comparative study. PARTICIPANTS: Twenty-one healthy subjects.
      METHODS: Intraocular pressure was measured in random order with four tonometers,
      first sitting then after 10 min of lying. MAIN OUTCOME MEASURES: Average postural
      intraocular pressure change (mmHg) and the 95% limits of agreement for measuring
      postural intraocular pressure change between tonometers. RESULTS: Average
      postural intraocular pressure change (lying minus sitting, mmHg) was measured
      highest with the Goldmann applanation tonometer (4.1 +/- 2.6) and Pneumatonometer
      (3.9 +/- 2.1), significantly lower with the Tonopen (0.9 +/- 1.7) and was
      negative with the Icare (-0.9 +/- 3.3). The 95% limits of agreement for measuring
      postural intraocular pressure change between Goldmann applanation tonometer and
      Icare, Pneumatonometer and Tonopen were -3.2-13.3, -6.4-6.9 and -2.8-9.4 mmHg,
      respectively. CONCLUSIONS: Postural change in intraocular pressure was measured
      similarly, on average, with Goldmann applanation tonometer and Pneumatonometer,
      and much lower with Tonopen and Icare Pro. There was poor interdevice agreement
      in measuring this parameter. We observed high intersubject variability,
      suggesting the clinical importance of this measurement in the diagnosis and
      management of glaucoma.

PMID- 24299103
TI  - Genome analysis of seven species of Kengyilia (Triticeae: Poaceae) with FISH and
      GISH.
AB  - The genome compositions and genetic relationships of seven species of Kengyilia
      were assessed using a sequential fluorescence in situ hybridization (FISH) and
      genomic in situ hybridization (GISH) technique. Five species, K. kokonorica, K.
      rigidula, K. hirsuta, K. grandiglumis, and K. thoroldiana, are native to Qinghai
      (China). The other two, K. alatavica and K. batalinii, are distributed in
      Xinjiang (China) and Kyrgyzstan, respectively. Each chromosome could be easily
      identified using chromosome markers (45S rDNA, 5S rDNA, pAs1, and AAG repeats) by
      FISH and allocated to the St, P, or Y genome by GISH. Molecular karyotype
      comparison indicated that K. alatavica and K. batalinii were distinct from the
      Qinghai species in all three genomes. These results support that the species of
      Kengyilia from Central Asia and the Qinghai-Tibetan plateau have independent
      origins. Genomic differentiation was still detected among the species of
      Kengyilia from Qinghai. Specifically, a common species-specific pericentric
      inversion was identified in both K. grandiglumis and K. thoroldiana, and an
      identical St-P non-Robertsonian translocation was frequently detected in K.
      hirsuta. The Qinghai species formed three genetic groups, K. kokonorica-K.
      rigidula, K. hirsuta, and K. grandiglumis-K. thoroldiana. The possible role of
      species-specific inversions and translocations in the evolution of StPY species
      is discussed. 

PMID- 24299104
TI  - Amplifying long transcripts of ryanodine receptors of five agricultural pests by
      transcriptome analysis and gap filling.
AB  - Ryanodine receptor (RyR) is an intracellular calcium release channel that plays a
      key role in excitation contraction coupling. Insect RyR is the target of diamide
      insecticides. Better understanding of insect RyR is necessary for studying the
      molecular mode of action and potential resistance mechanism of diamide
      insecticides. However, molecular manipulation of the full RyR gene is difficult
      because of its length (approximately 15 kb). At present, RyR genes have been
      reported only in a limited number of insects. Here, we developed an efficient
      strategy to amplify full-length transcripts of insect RyR genes. First, we
      searched the transcriptomes of five insects, Bemisia tabaci, Cnaphalocrocis
      medinalis, Chilo suppressalis, Laodelphgax striatellus, and Plutella xylostella,
      yielding 85 RyR contigs in total. Second, the relative positions of these contigs
      in RyR transcripts were determined by aligning them with 12 well-annotated RyRs.
      Third, we designed primers to fill gaps between contigs and used rapid
      amplification of cDNA ends (RACE) to amplify both 5'- and 3'-ends. Last, we
      assembled all fragments into long transcripts. As a result, full-length
      transcripts of three insects, C. suppressalis, L. striatellus, and P. xylostella,
      were obtained. The RyR transcript of B. tabaci was near full length, containing
      an intact ORF. Northern blot analysis indicated that RyR genes were expressed in
      all five insects. Sequence analyses showed that the amplified insect segments
      contained typical RyRs characteristics, such as EF-hand, motif GVRAGGGIGD, and
      six transmembrane domains. Seven lepidopteran-specific amino acid residues were
      found to be located in the C-terminal region of RyR proteins, which might be
      associated with the specificity of RyRs to diamide insecticides. 

PMID- 24299105
TI  - Mapping and candidate genes associated with saccharification yield in sorghum.
AB  - Sorghum (Sorghum bicolor (L.) Moench) is a high-yielding, stress tolerant energy
      crop for lignocellulosic-based biofuel production. Saccharification is a process
      by which hydrolytic enzymes break down lignocellulosic materials to fermentable
      sugars for biofuel production, and mapping and identifying genes underlying
      saccharification yield is an important first step to genetically improve the
      plant for higher biofuel productivity. In this study, we used the ICRISAT sorghum
      mini core germplasm collection and 14 739 single nucleotide polymorphism markers
      to map saccharification yield. Seven marker loci were associated with
      saccharification yield and five of these loci were syntenic with regions in the
      maize genome that contain quantitative trait loci underlying saccharification
      yield and cell wall component traits. Candidate genes from the seven loci were
      identified but must be validated, with the most promising candidates being beta
      tubulin, which determines the orientation of cellulose microfibrils in plant
      secondary cell walls, and NST1, a master transcription factor controlling
      secondary cell wall biosynthesis in fibers. Other candidate genes underlying the
      different saccharification loci included genes that play a role in vascular
      development and suberin deposition in plants. The identified loci and candidate
      genes provide information into the factors controlling saccharification yield and
      may facilitate increasing biofuel production in sorghum. 

PMID- 24299106
TI  - Molecular and classical chromosomal techniques reveal diversity in bushcricket
      genera of Barbitistini (Orthoptera).
AB  - The cytogenetic characteristics of 17 species of bushcricket belonging to eight
      genera of the tribe Barbitistini were examined by fluorescence in situ
      hybridization with 18S rDNA and (TTAGGn) telomeric as probes and by C-banding,
      silver, and fluorochrome staining. These markers were used to understand
      chromosomal organization and evolutionary relationships between genera or species
      within the same genus. The number of 18S rDNA clusters per haploid genome that co
      localized with active nucleolus organizer regions (NORs) ranged from one to five,
      with the most common pattern being the presence of one NOR-bearing chromosome.
      This ribosomal cistron was preferentially located in the paracentromeric region
      of autosomes and very rarely in the sex chromosome. The results demonstrated
      coincidence between the localization of major ribosomal genes and active NORs and
      the position of C-band and GC-rich regions. The rDNA/NOR distribution and the
      composition of chromosome heterochromatin proved to be good cytogenetic markers
      for distinguishing species and phylogenetic lines and for understanding the
      genomic differentiation and evolution of Barbitistini. A comparison of
      cytogenetic and morphological or behavioral traits suggests that morphological
      and behavioral specialization in this group was not followed by major karyotype
      modification (except for Leptophyes). However, the occurrence and distribution of
      different repetitive DNA sites tends to vary among the taxa. 

PMID- 24299107
TI  - Characterization and analysis of an industrial strain of Streptomyces
      bingchenggensis by genome sequencing and gene microarray.
AB  - Streptomyces bingchenggensis is a soil bacterium that produces milbemycins, a
      family of macrolide antibiotics that are commercially important in crop
      protection and veterinary medicine. In addition, S. bingchenggensis produces many
      other natural products including the polyether nanchangmycin and novel cyclic
      pentapeptides. To identify the gene clusters involved in the biosynthesis of
      these compounds, and better clarify the biochemical pathways of these gene
      clusters, the whole genome of S. bingchenggensis was sequenced, and the
      transcriptome profile was subsequently investigated by microarray. In comparison
      with other sequenced genomes in Streptomyces, S. bingchenggensis has the largest
      linear chromosome consisting of 11 936 683 base pairs (bp), with an average GC
      content of 70.8%. The 10 023 predicted protein-coding sequences include at least
      47 gene clusters correlated with the biosynthesis of known or predicted secondary
      metabolites. Transcriptional analysis demonstrated an extremely high expression
      level of the milbemycin gene cluster during the entire growth period and a
      moderately high expression level of the nanchangmycin gene cluster during the
      initial hours that subsequently decreased. However, other gene clusters appear to
      be silent. The genome-wide analysis of the secondary metabolite gene clusters in
      S. bingchenggensis, coupled with transcriptional analysis, will facilitate the
      rational development of high milbemycins-producing strains as well as the
      discovery of new natural products. 

PMID- 24299108
TI  - Comparative genomic organization and tissue-specific transcription of the
      duplicated fabp7 and fabp10 genes in teleost fishes.
AB  - A whole-genome duplication (WGD) early in the teleost fish lineage makes fish
      ideal organisms to study the fate of duplicated genes and underlying evolutionary
      trajectories that have led to the retention of ohnologous gene duplicates in fish
      genomes. Here, we compare the genomic organization and tissue-specific
      transcription of the ohnologous fabp7 and fabp10 genes in medaka, three-spined
      stickleback, and spotted green pufferfish to the well-studied duplicated fabp7
      and fabp10 genes of zebrafish. Teleost fabp7 and fabp10 genes contain four exons
      interrupted by three introns. Polypeptide sequences of Fabp7 and Fabp10 show the
      highest sequence identity and similarity with their orthologs from vertebrates.
      Orthology was evident as the ohnologous Fabp7 and Fabp10 polypeptides of teleost
      fishes each formed distinct clades and clustered together with their orthologs
      from other vertebrates in a phylogenetic tree. Furthermore, ohnologous teleost
      fabp7 and fabp10 genes exhibit conserved gene synteny with human FABP7 and
      chicken FABP10, respectively, which provides compelling evidence that the
      duplicated fabp7 and fabp10 genes of teleost fishes most likely arose from the
      well-documented WGD. The tissue-specific distribution of fabp7a, fabp7b, fabp10a,
      and fabp10b transcripts provides evidence of diverged spatial transcriptional
      regulation between ohnologous gene duplicates of fabp7 and fabp10 in teleost
      fishes. 

PMID- 24299109
TI  - Neuregulin-1 alpha, the underestimated molecule: emerging new roles in normal
      brain function and the pathophysiology of schizophrenia?
AB  - We comment here, from a schizophrenia research perspective, on a recent paper of
      Ghahramani Seno et al., which clearly shows that the splice variant neuregulin-1
      alpha is able to regulate multiple genes involved in phosphorylation,
      acetylation, and generation of splice variants. 

PMID- 24299110
TI  - Clinical significance of nonhabitual seizures during intracranial EEG monitoring.
AB  - This study sought to determine the frequency and clinical significance of
      nonhabitual seizures in 101 consecutive patients undergoing presurgical
      intracranial electroencephalography intracranial (icEEG) recording. We compared
      clinical data, recording details, and postsurgical outcome in patients with
      nonhabitual seizures to those without nonhabitual seizures during icEEG. In
      patients with nonhabitual seizures we compared icEEG recordings of nonhabitual
      seizures to recordings of habitual seizures. Nonhabitual seizures were recorded
      in 10% of patients. Those patients had a significantly higher rate of procedure
      related complications compared to patients without nonhabitual seizures. Ultimate
      seizure outcome did not differ between the groups. Nonhabitual seizures often
      occurred within the first 3 days of icEEG recording and had larger seizure-onset
      zones compared to the patient's habitual seizures. Nonhabitual seizures have no
      effect on outcome of epilepsy surgery but may serve as important markers of
      procedure-related complications during icEEG.

PMID- 24299111
TI  - Myositis facilitates preclinical accumulation of pathological prion protein in
      muscle.
AB  - BACKGROUND: In human and animal prion diseases, pathological prion protein,
      PrPSc, as well as prion infectivity is mainly found in the central nervous
      system, but also in lymphoid organs and muscle. Pathophysiology of prion
      colonization of lymphoid organs has been studied intensively, yet how myositis
      influences prion accumulation in muscle is unknown. RESULT: We have investigated
      the influence of myositis on PrPSc accumulation and prion infectivity in two
      distinct mouse models of experimental autoimmune myositis. Furthermore, we have
      addressed the relevance of PrPC expression in the lymphoreticular system in
      myositis by generating bone marrow chimeras.Here we show that myositis positively
      influences muscular PrPSc accumulation at preclinical time points and that PrPC
      expression in the lymphoid system is critical for this. In muscle, PrPSc and
      prion infectivity are uncoupled with detectable PrPSc but no prion infectivity at
      preclinical time points. Muscle has an intrinsically high ability to clear PrPSc
      once myositis has ceased, possibly involving autophagy. CONCLUSION: Our findings
      provide new insights into the pathophysiology of prion colonization in muscle
      pointing out that myositis leads to enhanced prion colonization of muscle in
      subclinical prion disease.

PMID- 24299112
TI  - Evaluating PET-CT in routine surveillance and follow-up after treatment for
      cervical cancer: a cost-effectiveness analysis.
AB  - OBJECTIVE: To undertake a cost-effectiveness analysis that compares positron
      emission tomography - computed tomography (PET-CT) imaging plus standard practice
      with standard practice alone in the diagnosis of recurrent or persistent cervical
      cancer during routine surveillance and follow-up of women who have previously
      been diagnosed and treated. DESIGN: Model-based economic evaluation using data
      from a systematic review, supplemented with data from other sources, and taking a
      UK National Health Service (NHS) perspective. SETTING: Secondary Care in England.
      POPULATION: Women at least 3 months after the completion of treatment, with
      either recurrent or persistent cervical cancer. METHODS: A state transition
      (Markov) model was developed using TreeAge Pro 2011. The structure of the model
      was informed by the reviews of the trials and clinical input. In the model, two
      diagnostic strategies were examined. A one-way sensitivity analysis,
      probabilistic sensitivity analysis, and a value of information analysis were also
      carried out. MAIN OUTCOME MEASURES: Cost-effectiveness based on incremental cost
      per quality-adjusted life year (QALY). RESULTS: Adding PET-CT to the current
      treatment strategy of clinical examination and scanning [magnetic resonance
      imaging (MRI) and/or CT scan] during the routine surveillance and follow-up of
      women with recurrent or persistent cervical cancer is significantly more costly,
      with only a minimal increase in effectiveness. The incremental cost-effectiveness
      ratio (ICER) for the strategy of PET-CT as an adjunct to the standard treatment
      strategy that included clinical examination, MRI, and/or CT scan, compared with
      the usual treatment alone, was over L1 million per QALY. CONCLUSION: The results
      of the current analysis suggest that use of PET-CT in the diagnosis of recurrent
      or persistent cervical cancer is not cost-effective. Current guidelines
      recommending imaging using PET-CT as a diagnostic or surveillance tool need to be
      reconsidered in light of these results. This study did not specifically
      investigate the use of PET-CT in women with symptoms and radiological suspicion
      of recurrence where exenteration was considered. More research in that specific
      area is required.

PMID- 24299113
TI  - Porous inorganic membranes for CO2 capture: present and prospects.

PMID- 24299114
TI  - Hard and soft tissue changes around implants installed in regular-sized and
      reduced alveolar bony ridges. An experimental study in dogs.
AB  - OBJECTIVE: To study bony and soft tissue changes at implants installed in
      alveolar bony ridges of different widths. MATERIAL AND METHODS: In 6 Labrador
      dogs, the mandibular premolars and first molars were extracted, and a buccal
      defect was created in the left side at the third and fourth premolars by removing
      the buccal bone and the inter-radicular and interdental septa. Three months after
      tooth extraction, full-thickness mucoperiosteal flaps were elevated, and implants
      were installed, two at the reduced (test) and two at the regular-sized ridges
      (control). Narrow or wide abutments were affixed to the implants. After 3 months,
      biopsies were harvested, and ground sections prepared for histological
      evaluation. RESULTS: A higher vertical buccal bony crest resorption was found at
      the test (1.5 +/- 0.7 mm and 1.0 +/- 0.7 mm) compared to the control implants
      (1.0 +/- 0.5 mm and 0.7 +/- 0.4 mm), for both wide and narrow abutment sites. A
      higher horizontal alveolar resorption was identified at the control compared to
      the test implants. The difference was significant for narrow abutment sites. The
      peri-implant mucosa was more coronally positioned at the narrow abutment, in the
      test sites, while for the control sites, the mucosal adaptation was more coronal
      at the wide abutment sites. These differences, however, did not reach statistical
      significance. CONCLUSIONS: Implants installed in regular-sized alveolar ridges
      had a higher horizontal, but a lower vertical buccal bony crest resorption
      compared to implants installed in reduced alveolar ridges. Narrow abutments in
      reduced ridges as well as wide abutments in regular-sized ridges yielded less
      soft tissue recession compared to their counterparts.

PMID- 24299115
TI  - R-wave sensing in an implantable cardiac monitor without ECG-based preimplant
      mapping: results from a multicenter clinical trial.
AB  - INTRODUCTION: Reducing the form factor of an implantable cardiac monitor (ICM)
      may simplify device implant. This study evaluated R-wave sensing at a range of
      electrode distances and a preferred device implant location without mapping.
      METHODS: Patients scheduled for a Medtronic Reveal(r) ICM implant (Medtronic
      Inc., Minneapolis, MN, USA) underwent a preimplant pocket recording using a
      diagnostic recording catheter. The ICM implant location was left to the
      discretion of the implanting physician, but a "recommended" position spanned the
      V2 -V3 electrocardiogram electrode location in an oblique 45 degrees  angle. R
      wave amplitudes were analyzed from ICM follow-up. RESULTS: Seventeen of 41
      subjects (15 male, age 57 +/- 16 years) had the maximum surface-filtered R-wave
      at the recommended location. Fourteen patients underwent diagnostic recording
      across the range of electrode spacing. There was a strong correlation between the
      R-wave amplitude and electrode distance (r(2) = 0.97, P < 0.001) with an increase
      of 29 MUV per 2.5 mm. Comparing normalized R-wave distributions between the
      recommended ICM implant group (Group 1, n = 19) and the remaining patients (Group
      2, n = 7), the proportion of ICM R-wave counts of amplitude 0.25-1.2 mV was
      higher (79% vs 46%, P < 0.05). Of 17 patients in Group 1 who had >= 1-month ICM
      follow-up (79 +/- 45 days), no sensing-related false arrhythmia detection was
      found in 16 (93%) patients. CONCLUSIONS: The subcutaneous R-wave amplitude
      correlates with electrode spacing in the implant zone of ICM patients. Implant
      locations at the V2 -V3 position at a 45 degrees  angle offer an adequate R wave
      for sensing. Preimplant mapping to achieve acceptable R-wave amplitude may not be
      necessary.

PMID- 24299117
TI  - Azaisoquinolinones: N positions tell you different stories in their optical
      properties.
AB  - Since isoquinolinones and their derivatives have been demonstrated to be powerful
      building blocks in constructing larger acenes and twistacenes, azaisoquinolinones
      and their analogues could also be important intermediates to approach larger N
      heteroacenes. In this paper, we are interested in developing a concise method to
      synthesize novel azaisoquinolinones building blocks and studying their physical
      properties. Our results showed that the different N positions have a large effect
      on the optical and electrochemical properties of azaisoquinolinones. For example,
      protonation of 6- and 7-azaisoquinolinones shows different shifts of UV-vis and
      FL spectra. More interestingly, 6- and 7-azaisoquinolinones exhibited different
      interactions with metal ions in CH3CN solution. Upon the addition of 2 equiv of
      Fe(3+), 6-azaisoquinolinone displayed an absorption wavelength red-shifted from
      470 to 540 nm (Deltalambda = 70 nm) with a color change from yellow to red, while
      the interaction between Fe(3+) and 7-azaisoquinolinone was very weak and there
      was no obvious color change (Deltalambda = 18 nm). Moreover, theoretical
      calculations confirmed the different optical properties with 6- and 7
      azaisoquinolinones. 

PMID- 24299116
TI  - Serum 25-hydroxyvitamin D concentration does not independently predict incident
      diabetes in older women.
AB  - AIMS: To investigate whether 25-hydroxyvitamin D concentration was associated
      with incident diabetes in a large cohort of older women. METHODS: Data were
      analysed from women included in the Study of Osteoporotic Fractures, a cohort of
      community-dwelling women aged >=65 years at enrolment. Serum 25-hydroxyvitamin D
      concentration was assessed at the year 6 visit, as were BMI and other factors
      associated with vitamin D and/or diabetes. Diabetes status was determined at each
      subsequent visit by self-report and medication use. Only those without prevalent
      diabetes at the year 6 visit were included in the present analysis (N = 5463,
      mean age 76.5 years). RESULTS: During a mean +/-sd follow-up of 8.6 +/- 4.4
      years, incident diabetes was reported in 320 participants. The mean BMI was
      higher in those with a 25-hydroxyvitamin D concentration <20 ng/ml (<50 nmol/l)
      than in those with concentrations 20-30 or >=30 ng/ml [50-74 or >=75 nmol/l (P <
      0.0001)]. A higher 25-hydroxyvitamin D concentration was associated with a 13%
      lower risk of incident diabetes after adjustment for age and clinic site [hazard
      ratio 0.87, 95% CI 0.76-0.99, per sd increase in 25-hydroxyvitamin D]; however,
      the addition of BMI to the model attenuated the estimated effect (hazard ratio
      0.97, 95% CI 0.86-1.11). Adjustment for additional potential confounders yielded
      similar results. CONCLUSIONS: Serum 25-hydroxyvitamin D does not independently
      predict incident diabetes in older women. Although those with higher 25
      hydroxyvitamin D concentrations are less likely to develop diabetes, this is
      mainly explained by their lower BMI.

PMID- 24299118
TI  - A pilot study of the effects of a tailored web-based intervention on promoting
      fruit and vegetable intake in African American families.
AB  - BACKGROUND: The current study examined the effects of a Web-based tailored
      parenting intervention on increasing fruit and vegetable intake in African
      American families. METHODS: Forty-seven African American parents (mean age, 41.32
      +/- 7.30; 93.6% female) with an adolescent (mean age, 13.32 +/- 1.46; 59.6%
      female) participated in a Web-based autonomy-support parenting tailored
      intervention session to increase both parent and youth fruit and vegetable (F&V)
      intake. The session lasted 45-60 minutes and included three phases: a feedback
      phase; a Web-based information phase, and a goal-setting and action plan phase.
      Self-reported measures of parenting skills [based on autonomy (choice), support,
      and communication] and F&V intake (assessed as average daily intake) were
      assessed at baseline and at a 1-week follow-up session. RESULTS: There was a
      significant increase in parents' self-reports of daily fruit intake from pretest
      to the 1-week follow-up. Parent and adolescent combined F&V intake also
      significantly increased from pretest to 1-week follow-up. Overall, parents
      reported that the program was easy to navigate and that they enjoyed
      participating in the Web-based online program. CONCLUSIONS: Current findings
      provide preliminary support for an autonomy-support parent tailored Web-based
      program for improving dietary intake in African American families.

PMID- 24299119
TI  - Image-level and group-level models for Drosophila gene expression pattern
      annotation.
AB  - BACKGROUND: Drosophila melanogaster has been established as a model organism for
      investigating the developmental gene interactions. The spatio-temporal gene
      expression patterns of Drosophila melanogaster can be visualized by in situ
      hybridization and documented as digital images. Automated and efficient tools for
      analyzing these expression images will provide biological insights into the gene
      functions, interactions, and networks. To facilitate pattern recognition and
      comparison, many web-based resources have been created to conduct comparative
      analysis based on the body part keywords and the associated images. With the fast
      accumulation of images from high-throughput techniques, manual inspection of
      images will impose a serious impediment on the pace of biological discovery. It
      is thus imperative to design an automated system for efficient image annotation
      and comparison. RESULTS: We present a computational framework to perform
      anatomical keywords annotation for Drosophila gene expression images. The spatial
      sparse coding approach is used to represent local patches of images in comparison
      with the well-known bag-of-words (BoW) method. Three pooling functions including
      max pooling, average pooling and Sqrt (square root of mean squared statistics)
      pooling are employed to transform the sparse codes to image features. Based on
      the constructed features, we develop both an image-level scheme and a group-level
      scheme to tackle the key challenges in annotating Drosophila gene expression
      pattern images automatically. To deal with the imbalanced data distribution
      inherent in image annotation tasks, the undersampling method is applied together
      with majority vote. Results on Drosophila embryonic expression pattern images
      verify the efficacy of our approach. CONCLUSION: In our experiment, the three
      pooling functions perform comparably well in feature dimension reduction. The
      undersampling with majority vote is shown to be effective in tackling the problem
      of imbalanced data. Moreover, combining sparse coding and image-level scheme
      leads to consistent performance improvement in keywords annotation.

PMID- 24299121
TI  - Eyes on new product development.

PMID- 24299120
TI  - Controlled assembly of inorganic-organic frameworks based on [SeMo6O21]4-
      polyanion.
AB  - The chemical system based on [SeMo6O21](4-) polyanion and carboxylate ligand has
      been investigated. According to the inherent nature of organic groups, a series
      of selenomolybdates with three architectures have been isolated through rational
      and deliberate synthetic routes by stereospecific addition of different
      carboxylic acids. Such an approach is potentially interesting for {SeMo6}
      cluster, which exhibits a high surface nucleophilicity and is capable of being
      functionalized by covalently bound carboxylic acids. Investigation of the
      assemblies reveals that carboxylic acids have good flexibility and conformational
      freedom, representing the powerful chemical tools to control the polyanion
      assembly processes. 

PMID- 24299122
TI  - Bubble and pattern formation in liquid induced by an electron beam.
AB  - Liquid cell electron microscopy has emerged as a powerful technique for in situ
      studies of nanoscale processes in liquids. An accurate understanding of the
      interactions between the electron beam and the liquid medium is essential to
      account for, suppress, and exploit beam effects. We quantify the interactions of
      high energy electrons with water, finding that radiolysis plays an important
      role, while heating is typically insignificant. For typical imaging conditions,
      we find that radiolysis products such as hydrogen and hydrated electrons achieve
      equilibrium concentrations within seconds. At sufficiently high dose-rate, the
      gaseous products form bubbles. We image bubble nucleation, growth, and migration.
      We develop a simplified reaction-diffusion model for the temporally and spatially
      varying concentrations of radiolysis species and predict the conditions for
      bubble formation by H2. We discuss the conditions under which hydrated electrons
      cause precipitation of cations from solution and show that the electron beam can
      be used to "write" structures directly, such as nanowires and other complex
      patterns, without the need for a mask. 

PMID- 24299123
TI  - Yucasin is a potent inhibitor of YUCCA, a key enzyme in auxin biosynthesis.
AB  - Indole-3-acetic acid (IAA), an auxin plant hormone, is biosynthesized from
      tryptophan. The indole-3-pyruvic acid (IPyA) pathway, involving the tryptophan
      aminotransferase TAA1 and YUCCA (YUC) enzymes, was recently found to be a major
      IAA biosynthetic pathway in Arabidopsis. TAA1 catalyzes the conversion of
      tryptophan to IPyA, and YUC produces IAA from IPyA. Using a chemical biology
      approach with maize coleoptiles, we identified 5-(4-chlorophenyl)-4H-1,2,4
      triazole-3-thiol (yucasin) as a potent inhibitor of IAA biosynthesis in YUC
      expressing coleoptile tips. Enzymatic analysis of recombinant AtYUC1-His
      suggested that yucasin strongly inhibited YUC1-His activity against the substrate
      IPyA in a competitive manner. Phenotypic analysis of Arabidopsis YUC1 over
      expression lines (35S::YUC1) demonstrated that yucasin acts in IAA biosynthesis
      catalyzed by YUC. In addition, 35S::YUC1 seedlings showed resistance to yucasin
      in terms of root growth. A loss-of-function mutant of TAA1, sav3-2, was
      hypersensitive to yucasin in terms of root growth and hypocotyl elongation of
      etiolated seedlings. Yucasin combined with the TAA1 inhibitor l-kynurenine acted
      additively in Arabidopsis seedlings, producing a phenotype similar to yucasin
      treated sav3-2 seedlings, indicating the importance of IAA biosynthesis via the
      IPyA pathway in root growth and leaf vascular development. The present study
      showed that yucasin is a potent inhibitor of YUC enzymes that offers an effective
      tool for analyzing the contribution of IAA biosynthesis via the IPyA pathway to
      plant development and physiological processes. 

PMID- 24299124
TI  - The impact of giving support to others on older adults' perceived health status.
AB  - BACKGROUND: Social support that may contribute to the physical and mental health
      of older adults is widely studied. However, much of the existing research has
      focused on the impact of receiving support; the effects of giving support have
      largely been neglected. Using the biopsychosocial perspective, this study aimed
      to examine the independent impact of giving support to others on older adults'
      perceived health status. METHODS: Data for this study were obtained from a
      nationwide community-based cross-sectional survey entitled 'Determinants of
      Wellness among Older Malaysians: A Health Promotion Perspective', which was
      conducted in 2010. To assess the unique effects of giving support on perceived
      health status, above and beyond other possible known factors, a four-step
      hierarchical regression model using SPSS was used to test the hypothesis.
      RESULTS: The findings from the analysis revealed that giving support to others
      was a significant positive predictor of older adults' perceived health status
      after receiving support, demographic variables and chronic medical conditions
      were considered. Further results showed that giving support to others had almost
      twice the effect on perceived health status (beta = 0.11, P < 0.001) as receiving
      support (beta = 0.06, P < 0.05). CONCLUSION: The findings from this study
      underscore the need to develop programmes that encourage older adults'
      participation in productive activities such as caring for and helping others and
      volunteering.

PMID- 24299125
TI  - Epidemiology, management, complications and costs associated with type 2 diabetes
      in Brazil: a comprehensive literature review.
AB  - BACKGROUND: With an estimated 74% of all deaths attributable to non-communicable
      diseases (NCDs) in 2010, NCDs have become a major health priority in Brazil. The
      objective of the study was to conduct a comprehensive literature review on
      diabetes in Brazil; specifically: the epidemiology of type 2 diabetes, the
      availability of national and regional sources of data (particularly in terms of
      direct and indirect costs) and health policies for the management of diabetes and
      its complications. METHODS: A literature search was conducted using PubMed to
      identify articles containing information on diabetes in Brazil. Official
      documents from the Brazilian government and the World Health Organization, as
      well as other grey literature and official government websites were also
      reviewed. RESULTS: From 2006 to 2010, an approximate 20% increase in the
      prevalence of self-reported diabetes was observed. In 2010, it was estimated that
      6.3% of Brazilians aged 18 years or over had diabetes. Diabetes was estimated to
      be responsible for 278,778 years of potential life lost for every 100,000 people.
      In 2013, it is estimated that about 7% of patients with diabetes has had one or
      more of the following complications: diabetic foot ulcers, amputation, kidney
      disease, and fundus changes. The estimated annual direct cost of diabetes was USD
      $3.952 billion in 2000; the estimated annual indirect cost was USD $18.6 billion.
      The two main sources of data on diabetes are the information systems of the
      Ministry of Health and surveys. In the last few years, the Brazilian Ministry of
      Health has invested considerably in improving surveillance systems for NCDs as
      well as implementing specific programmes to improve diagnosis and access to
      treatment. CONCLUSIONS: Brazil has the capacity to address and respond to NCDs
      due to the leadership of the Ministry of Health in NCD prevention activities,
      including an integrated programme currently in place for diabetes. Strengthening
      the surveillance of NCDs is a national priority along with recognising the urgent
      need to invest in improving the coverage and quality of mortality data. It is
      also essential to conduct regular surveys of risk factors on a national scale in
      order to design effective preventive strategies.

PMID- 24299126
TI  - Dependence of the endangered black-capped Vireo on sustained cowbird management.
AB  - Conservation-reliant species depend on active management, even after surpassing
      recovery goals, for protection from persistent threats. Required management may
      include control of another species, habitat maintenance, or artificial
      recruitment. Sometimes, it can be difficult to determine whether sustained
      management is required. We used nonspatial stochastic population projection
      matrix simulation and a spatially explicit population model to estimate the
      effects of parasitism by a brood parasite, the Brown-headed Cowbird (Moluthrus
      ater), on a population of endangered Black-capped Vireos (Vireo atricapilla). We
      simulated parasitism as a percentage of breeding vireo pairs experiencing
      decreased fecundity due to cowbirds. We estimated maximum sustainable parasitism
      (i.e., highest percentage of parasitized vireo breeding pairs for which
      population growth is >=1) with the nonspatial model under multiple scenarios
      designed to assess sensitivity to assumptions about population growth rate,
      demographic effects of parasitism, and spatial distribution of parasitism. We
      then used the spatially explicit model to estimate cumulative probabilities of
      the population falling below the population recovery target of 1000 breeding
      pairs for a range of parasitism rates under multiple scenarios. We constructed
      our models from data on vireos collected on the Fort Hood Military Reservation,
      Texas (U.S.A.). Estimates of maximum sustainable parasitism rates ranged from 9
      12% in scenarios with a low (6%) vireo population growth rate to 49-60% in
      scenarios with a high (24%) growth rate. Sustained parasitism above 45-85%,
      depending on the scenario, would likely result in the Fort Hood Vireo population
      dropping below its recovery goal within the next 25 years. These estimates
      suggest that vireos, although tolerant of low parasitism rates, are a
      conservation-reliant species dependent on cowbird management.

PMID- 24299127
TI  - The inheritance of extra-hepatic portosystemic shunts and elevated bile acid
      concentrations in Maltese dogs.
AB  - OBJECTIVES: To determine the heritability of extra-hepatic portosystemic shunts
      and elevated post-prandial serum bile acid concentrations in Maltese dogs.
      MATERIALS AND METHODS: Maltese dogs were recruited and investigated by a variable
      combination of procedures including dynamic bile acid testing, rectal ammonia
      tolerance testing, ultrasonography, portal venography, surgical inspection or
      necropsy. In addition, nine test matings were carried out between affected and
      affected dogs, and affected and unaffected dogs. RESULTS: In 135 variably related
      Maltese, shunt status could be confirmed in 113, including 19 with an extra
      hepatic portosystemic shunt (17 confirmed at surgery, 2 at necropsy). Rectal
      ammonia tolerance testing results and post-prandial serum bile acid
      concentrations were retrievable for 50 and 88 dogs, respectively. Pedigree
      information was available for these 135 and an additional 164 related dogs. Two
      consecutive test matings were carried out between two affected animals (whose
      shunts had been attenuated), with 2 of 8 (25%) of offspring having an extra
      hepatic portosystemic shunt. Six test matings were carried out between an
      affected and an unaffected animal, with 2 of 22 (9%) offspring affected.
      Heritability of extra-hepatic portosystemic shunt was 0.61 calculated using
      variance components analysis [95% confidence interval (CI) 0.14 to 1.0, P=0.001].
      The best fitting model from segregation analysis was a common, partially
      penetrant, recessive model (allele frequency 0.34, penetrance 0.99, CI 0.09 to
      1.0). The heritability of elevated post-prandial serum bile acid (and thus likely
      portal vein hypoplasia) was 0.81 (CI 0.43 to 1.0, P=0.2) after logarithmic
      transformation of post-prandial serum bile acid concentrations. CLINICAL
      SIGNIFICANCE: There is strong support for extra-hepatic portosystemic shunts and
      elevated post-prandial serum bile acid concentrations both being inherited
      conditions in Maltese.

PMID- 24299128
TI  - Maternal sensitivity: observational studies honoring Mary Ainsworth's 100(th)
      year.

PMID- 24299129
TI  - Mary D. Salter Ainsworth: an autobiographical sketch. 1983.

PMID- 24299130
TI  - Revisiting Mary Ainsworth's conceptualization and assessments of maternal
      sensitivity-insensitivity.
AB  - This paper describes the evolution of Ainsworth's construct of maternal
      sensitivity-insensitivity to infant signals from its beginnings in her research
      in Uganda to its explicit emergence in the findings from the Baltimore study. It
      provides an analysis of her bipolar Maternal Care Scales (Sensivity
      Insensitivity, Cooperation-Interference, Acceptance-Rejection, and Accessibility
      Ignoring and Neglecting) and associated findings from the Baltimore study,
      including studies of specific maternal and infant interactive behaviors also
      rooted in the sensitivity construct. In addition, the four Maternal Care ratings
      of observed maternal behavior in the home environment are considered in relation
      to Strange Situation subgroups and Ainsworth's home classifications of infant
      attachment and exploratory behavior. A brief comparison of Ainworth's with
      Bowlby's contributions follows. The paper ends with a discussion of Ainsworth's
      approach to science.

PMID- 24299131
TI  - Mary Ainsworth's legacy: a systematic review of observational instruments
      measuring parental sensitivity.
AB  - Since Mary Ainsworth's formulation of the Sensitivity-Insensitivity to Infant
      Signals and Communications observational scale, new instruments have been
      developed to observe parental sensitivity. In this paper, we provide an overview
      of eight commonly used observational instruments to measure parental sensitivity.
      Their similarities and differences in comparison to the original Ainsworth
      sensitivity construct and its applications will be discussed. Consistent with the
      search criteria, each of the instruments clearly includes the key elements of
      Ainsworth's definition of sensitivity. Notable deviations from the original scale
      are the use of composite scales rather than a single global scale and the related
      inclusion of new elements, and specifically the inclusion of positive affect as
      an indicator of sensitivity. Further, most of the instruments have a wider scope
      than Ainsworth's sensitivity scale in terms of target age groups and the
      assessment of sensitivity in fathers. We discuss the interpretation of the
      sensitivity construct depending on variations in how the construct is defined in
      different observational instruments, and advances in the application of the
      construct. 

PMID- 24299133
TI  - Sensitive attunement to infants' internal states: operationalizing the construct
      of mind-mindedness.
AB  - This paper focuses on caregiver sensitivity, its relation to mind-mindedness
      (caregivers' attunement to their infants' internal states), and how well both
      constructs predict infant attachment security. The seminal Baltimore research on
      sensitivity and its relation to attachment security is summarized, highlighting
      the conclusion that mothers in the insecure-resistant and insecure-avoidant
      categories could not be distinguished on the basis of sensitivity. The contrast
      between the complex, sophisticated construct detailed in the original studies and
      the broad-based nature of the sensitivity coding scale is discussed. This paper
      argues that we should return to Ainsworth, Bell, and Stayton's (1971, 1974)
      original emphasis on the caregiver's ability to perceive things from the child's
      point of view in defining a measure of the quality of early infant-caregiver
      interaction. This approach led to the development of the construct of mind
      mindedness. There are two mind-mindedness indices: caregivers' tendency during
      infant-caregiver interaction to (a) comment appropriately on their infants'
      putative thoughts and feelings (appropriate mind-related comments), and (b)
      misread their infants' internal states (non-attuned mind-related comments). Both
      indices predict independent variance in infant-caregiver attachment security, and
      together can distinguish between the secure, avoidant, and resistant categories.
      The specific, multidimensional nature of mind-mindedness complements the global
      construct of sensitivity.

PMID- 24299132
TI  - Parental synchrony and nurturance as targets in an attachment based intervention:
      building upon Mary Ainsworth's insights about mother-infant interaction.
AB  - As an astute observer of parent-infant interaction, Mary Ainsworth described and
      assessed facets of maternal sensitivity, including responsiveness to conditions
      of infant distress and non-distress. This paper considers the importance of
      distinguishing between parental sensitivity to children's distress cues (which we
      refer to as nurturance) and parental sensitivity to children's non-distress cues
      (which we refer to as synchrony). Observations of parents in our intervention,
      Attachment and Biobehavioral Catch-up (ABC), have led us to believe that distress
      and non-distress represent distinct contexts in which parents can be
      differentially sensitive or insensitive in responding. Thus, we have
      conceptualized nurturance and synchrony as distinct targets of the ABC
      intervention and, in deciding how to assess parental sensitivity, we have chosen
      measures that distinguish between nurturance and synchrony. This paper describes
      the strengths and weaknesses of different approaches we have taken to assess
      parental sensitivity, including diary methodology that we developed for assessing
      parental nurturance and global measures that we have used for assessing parental
      synchrony. Finally, a frequency-based coding system is described that we
      developed for assessing parental nurturance and synchrony from videotaped
      intervention sessions.

PMID- 24299134
TI  - The insightfulness assessment: measuring the internal processes underlying
      maternal sensitivity.
AB  - In her description of sensitive mothers, Ainsworth described not only maternal
      behaviors but also the internal processes underlying such behavior, including the
      capacity to "see things from the child's point of view". Ainsworth assessed this
      capacity from her extensive observations of mothers interacting with their
      infants, from records of mothers' talk to the babies, and from brief interviews
      about their babies. Attachment researchers following Ainsworth focused primarily
      on observations of maternal sensitive behavior, however, and the processes
      underlying such behavior were mostly inferred from the mothers' behavior. The
      Insightfulness Assessment (IA), a video replay procedure in which mothers are
      interviewed regarding their children's thoughts and feelings after they watch
      brief video clips of their children, was developed to assess systematically and
      directly the mother's ability to take the child's perspective. This paper uses
      examples from the IA to show how it captures many of the internal processes
      underlying caregiving behavior which Ainsworth described. Data supporting the
      IA's validity is reviewed, which suggest that the IA can complement observations
      of mothers' caregiving behavior in order to obtain a more comprehensive
      assessment of maternal sensitivity.

PMID- 24299135
TI  - Parsing the construct of maternal insensitivity: distinct longitudinal pathways
      associated with early maternal withdrawal.
AB  - The current paper expands on Ainsworth's seminal construct of maternal
      sensitivity by exploring the developmental pathways associated with one
      particular form of insensitivity: maternal withdrawal. Drawing on longitudinal
      data from infancy to age 20 in a high-risk cohort, we highlight how maternal
      withdrawal over the first eight years of life is associated with child caregiving
      behavior and with maternal role confusion, as well as with features of borderline
      and antisocial personality disorders. We also present evidence for the
      specificity of this pathway in relation to other aspects of maternal
      insensitivity and other aspects of child adaptation. To illuminate these pathways
      we both review recent published work and report new findings on the middle
      childhood and adolescent components of these trajectories. Finally, we consider
      the implications for assessment of maternal behavior in high-risk samples and
      indicate directions for productive future work.

PMID- 24299136
TI  - How does microanalysis of mother-infant communication inform maternal sensitivity
      and infant attachment?
AB  - Microanalysis research on 4-month infant-mother face-to-face communication
      operates like a "social microscope" and identifies aspects of maternal
      sensitivity and the origins of attachment with a more detailed lens. We hope to
      enhance a dialogue between these two paradigms, microanalysis of mother-infant
      communication and maternal sensitivity and emerging working models of attachment.
      The prediction of infant attachment from microanalytic approaches and their
      contribution to concepts of maternal sensitivity are described. We summarize
      aspects of one microanalytic study by Beebe and colleagues published in 2010 that
      documents new communication patterns between mothers and infants at 4 months that
      predict future disorganized (vs. secure) attachment. The microanalysis approach
      opens up a new window on the details of the micro-processes of face-to-face
      communication. It provides a new, rich set of behaviors with which to extend our
      understanding of the origins of infant attachment and of maternal sensitivity.

PMID- 24299137
TI  - One doll fits all: validation of the Leiden Infant Simulator Sensitivity
      Assessment (LISSA).
AB  - Children vary hugely in how demanding of their caregivers they are. This creates
      differences in demands on parents during observation, making the comparison of
      sensitivity between parents difficult. It would therefore be of interest to
      create standard situations in which all caregivers are faced with the same level
      of demand. This study developed an ecologically valid but standardized setting
      using an infant simulator with interactive features, the Leiden Infant Simulator
      Sensitivity Assessment (LISSA). The infant simulator resembles a real infant in
      appearance and it produces crying sounds that are life-like. The simulator begins
      with fussing and progresses to more intense crying in case of no care or
      inappropriate care. It responds by being calm again if appropriate care is given.
      One hundred and eighty-one female participants took care of the infant simulator
      for two evenings and in a 30 min lab session with increasing competing demands.
      Sensitive parenting behavior during the lab session was coded with the Ainsworth
      Sensitivity Scale. Sensitivity ratings covered the whole range of the scale (1
      9), and were stable across settings (free play, competing demands). Sensitivity
      was related to an increase of positive affect during caretaking, and
      insensitivity was related to intended harsh caregiving response during a
      computerized cry paradigm. Sensitivity was unrelated to social desirability and
      self-reported quality of care given to the infant simulator. We discuss the
      potentials of the infant simulator for research on sensitive parenting, for
      preventive interventions, and for clinical practices.

PMID- 24299138
TI  - Maternal anxiety, maternal sensitivity, and attachment.
AB  - Previous research has related maternal anxiety to insecurity of attachment. Here
      we ask whether different aspects of maternal sensitivity mediate this link. From
      a community sample of intact families with 1-3 children, mothers with 4.5-year
      olds were selected for low, medium, or high anxiety levels (N = 98). Following
      Mary Ainsworth's lead, our maternal sensitivity measures were primarily based on
      ratings of direct observations. Six sets of measures were obtained: positive
      maternal style at home (a mean of four different ratings); providing a sensitive
      framework, limit setting, allowing autonomy, criticizing/cutting in (each a mean
      over two laboratory joint tasks); and tension-making (a mean of three different
      ratings in a fear-inducing task). Regression analyses showed firstly that
      maternal anxiety rather than behavioral inhibition or sex of child was the
      significant predictor of each maternal sensitivity measure; and secondly that
      these measures rather than maternal anxiety or sex were the significant
      predictors of security of attachment. Finally, ANOVA's indicated which sets of
      maternal ratings were associated with each pattern of attachment (Avoidant,
      Secure, Ambivalent, or Controlling).

PMID- 24299139
TI  - Piecing together the sensitivity construct: ethology and cross-cultural research.
AB  - Although Ainsworth and Bowlby's perspective on attachment relationships has
      instinctive underpinnings, they also recognized variability in the ways
      caregiving is implemented in different ecologies. Ainsworth's naturalistic
      observations in two different societies provided early evidence about the
      development of infant-mother attachment, differences in the quality of attachment
      relationships, and the role of maternal care in attachment development. Further,
      her research demonstrated the importance of an ethological approach for research
      within and across cultures. Employing similar concepts and methods, my
      collaborators and I have tested and expanded Bowlby's and Ainsworth's ideas about
      the generality of the sensitivity construct and sensitivity-security link. In our
      research, ethological observations have been key to elaborating the quality of
      care construct and studying child-mother attachment relationships in different
      cultures, social contexts, and ages.

PMID- 24299140
TI  - Individual dispositions as precursors of differences in attachment quality: why
      maternal sensitivity is nevertheless important.
AB  - This paper explores the interplay of maternal sensitivity (or, more generally,
      the quality of the caregiving social environment) and infant individual
      dispositions in predicting infant-mother attachment. After a brief theoretical
      introduction, the focus turns to studies conducted during the 1980s that
      predicted attachment security vs. insecurity at 12 months from newborns' ability
      to regulate orientation and arousal. A re-analysis of two longitudinal studies,
      formerly coded only with the ABC system, subsequently revealed that disorganized
      (vs. organized) attachment was predictable from newborns' regulatory abilities,
      whereas secure (vs. insecure) attachment was predictable from the quality of
      maternal care. This suggested that the two dichotomies represented distinct
      dimensions and that - in low risk samples - disorganized SSP behavior may be
      associated with infant behavioral dispositions. More recent attempts to predict
      disorganized attachment from infant genetic (as opposed to newborn behavioral)
      dispositions yielded inconsistent results when only main effects models were
      examined. A set of subsequent studies examining the interplay of genetic and
      caregiving influences in the prediction of disorganized attachment suggested that
      maternal sensitivity is of particular importance in cases of genetic risk.

PMID- 24299141
TI  - Epilogue: reflections on a Special Issue of Attachment & Human Development in
      Mary Ainsworth's 100(th) year.

PMID- 24299143
TI  - Point of care monitoring of hemodialysis patients with a breath ammonia
      measurement device based on printed polyaniline nanoparticle sensors.
AB  - A device for measuring human breath ammonia was developed based on a single use,
      disposable, inkjet printed ammonia sensor fabricated using polyaniline
      nanoparticles. The device was optimized for sampling ammonia in human breath
      samples by addressing issues such as variations in breath sample volume, flow
      rate, sources of oral ammonia, temperature and humidity. The resulting system was
      capable of measuring ammonia in breath from 40 to 2993 ppbv (r(2 )= 0.99, n = 3)
      as correlated with photoacoustic laser spectroscopy and correlation in normal
      human breath samples yielded a slope of 0.93 and a Pearson correlation
      coefficient of 0.9705 (p < 0.05, n = 11). Measurement of ammonia in the breath of
      patients with end-stage kidney disease demonstrated its significant reduction
      following dialysis, while also correlating well with blood urea nitrogen (BUN) (r
      = 0.61, p < 0.01, n = 96). Excellent intraindividual correlations were
      demonstrated between breath ammonia and BUN (0.86 to 0.96), which demonstrates
      the possibility of using low cost point of care breath ammonia systems as a
      noninvasive means of monitoring kidney dysfunction and treatment. 

PMID- 24299144
TI  - Same-day assessment and management of urgent (2-week wait) colorectal referrals:
      an analysis of the outcome of 1606 patients attending an endoscopy unit-based
      colorectal clinic.
AB  - AIM: The Rapid Access Diagnosis and Remedy (RADAR) clinic combines 2-week wait
      (TWW) specialist consultation with 'straight-to-test' flexible sigmoidoscopy (FS)
      for left-sided 'red-flag' TWW criteria (excluding right-sided mass or iron
      deficiency anaemia). The study aims were to determine the effectiveness of RADAR
      in differentiating colorectal cancer from benign disease and to evaluate the need
      for whole colonic investigation (WCI) following FS, in symptomatic patients.
      METHOD: Prospectively collated data of all RADAR patients from November 2005 to
      November 2009 were analysed, excluding patients referred internally for a FS. The
      local histology database was later interrogated to detect any missed cancers.
      RESULTS: Of 1690 patients (729 men; median (range) age: 68 (18-96) years)
      assessed in RADAR, 84 were excluded. Colorectal cancer (CRC) was diagnosed in 117
      (7.3%). Eighty-seven cancers were diagnosed on the day of attendance and a
      further 13 within a week (88.9% overall). Two patients after a cancer-free FS
      were found to have a right-sided CRC on WCI (0.24%) and one synchronous cancer
      was found. No patient with a cancer-free FS having a WCI was subsequently found
      to have CRC at a median of 35 (12-58) months. CONCLUSION: Flexible sigmoidoscopy,
      in the context of an endoscopy unit TWW clinic, allows same-day diagnosis of most
      patients referred with left-sided symptoms, and immediate reassurance and
      treatment of most benign diagnoses. For these patients, the use of routine WCI
      following a cancer-free FS does not appear to be beneficial. Adopting this system
      would significantly reduce the number of barium enemas and colonoscopies
      currently performed.

PMID- 24299146
TI  - Photogenerated carriers transfer in dye-graphene-SnO2 composites for highly
      efficient visible-light photocatalysis.
AB  - The visible-light-driven photocatalytic activities of graphene-semiconductor
      catalysts have recently been demonstrated, however, the transfer pathway of
      photogenerated carriers especially where the role of graphene still remains
      controversial. Here we report graphene-SnO2 aerosol nanocomposites that exhibit
      more superior dye adsorption capacity and photocatalytic efficiency compared with
      pure SnO2 quantum dots, P25 TiO2, and pure graphene aerosol under the visible
      light. This study examines the origin of the visible-light-driven photocatalysis,
      which for the first time links to the synergistic effect of the
      cophotosensitization of the dye and graphene to SnO2. We hope this concept and
      corresponding mechanism of cophotosensitization could provide an original
      understanding for the photocatalytic reaction process at the level of carrier
      transfer pathway as well as a brand new approach to design novel and versatile
      graphene-based composites for solar energy conversion. 

PMID- 24299145
TI  - Prevalence of vision impairment and refractive error in school children in Ba Ria
      - Vung Tau province, Vietnam.
AB  - BACKGROUND: To assess the prevalence of vision impairment and refractive error in
      school children 12-15 years of age in Ba Ria - Vung Tau province, Vietnam.
      DESIGN: Prospective, cross-sectional study. PARTICIPANTS: 2238 secondary school
      children. METHODS: Subjects were selected based on stratified multistage cluster
      sampling of 13 secondary schools from urban, rural and semi-urban areas. The
      examination included visual acuity measurements, ocular motility evaluation,
      cycloplegic autorefraction, and examination of the external eye, anterior
      segment, media and fundus. MAIN OUTCOME MEASURES: Visual acuity and principal
      cause of vision impairment. RESULTS: The prevalence of uncorrected and presenting
      visual acuity <=6/12 in the better eye were 19.4% (95% confidence interval, 12.5
      26.3) and 12.2% (95% confidence interval, 8.8-15.6), respectively. Refractive
      error was the cause of vision impairment in 92.7%, amblyopia in 2.2%, cataract in
      0.7%, retinal disorders in 0.4%, other causes in 1.5% and unexplained causes in
      the remaining 2.6%. The prevalence of vision impairment due to myopia in either
      eye (-0.50 diopter or greater) was 20.4% (95% confidence interval, 12.8-28.0),
      hyperopia (>=2.00 D) was 0.4% (95% confidence interval, 0.0-0.7) and emmetropia
      with astigmatism (>=0.75 D) was 0.7% (95% confidence interval, 0.2-1.2). Vision
      impairment due to myopia was associated with higher school grade and increased
      time spent reading and working on a computer. CONCLUSIONS: Uncorrected refractive
      error, particularly myopia, among secondary school children in Vietnam is a major
      public health problem. School-based eye health initiative such as refractive
      error screening is warranted to reduce vision impairment.

PMID- 24299147
TI  - Divergent total synthesis of the Lycopodium alkaloids huperzine A, huperzine B,
      and huperzine U.
AB  - Huperzine A, huperzine B, and huperzine U are congeners isolated from the Chinese
      herb Huperzia serrata (= Lycopodium serratum ) in minuscule amounts. The most
      efficient total synthesis of huperzine A, the first asymmetric total syntheses of
      huperzine B, and the first total synthesis of huperzine U have been achieved
      efficiently in overall yields of 17%, 10%, and 9%, respectively, each spanning 10
      13 steps from (R)-pulegone. The featured steps include palladium-catalyzed
      Buchwald-Hartwig coupling and Heck cyclization reactions and an Ir-catalyzed
      olefin isomerization reaction. This work has established the absolute
      configurations of huperzine B and huperzine U and revealed that natural huperzine
      A, huperzine B, and huperzine U possess the same set of absolute
      stereochemistries, thus providing support for the potential role of huperzine B
      and huperzine U in the biosynthesis of huperzine A. 

PMID- 24299148
TI  - Synthesis of carbocyclic and heterocyclic beta-aminocarboxylic acids.

PMID- 24299149
TI  - Detection and differentiation of neutral organic compounds by 19F NMR with a
      tungsten calix[4]arene imido complex.
AB  - Fluorinated tungsten calix[4]arene imido complexes were synthesized and used as
      receptors to detect and differentiate neutral organic compounds. It was found
      that the binding of specific neutral organic molecules to the tungsten centers
      induces an upfield shift of the fluorine atom appended on the arylimido group,
      the extent of which is highly dependent on electronic and steric properties. We
      demonstrate that the specific bonding and size-selectivity of calix[4]arene
      tungsten-imido complex combined with (19)F NMR spectroscopy is a powerful new
      method for the analysis of complex mixtures. 

PMID- 24299151
TI  - Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination
      cycles in women with polycystic ovary syndrome: a meta-analysis.
AB  - Polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian
      stimulation and intrauterine insemination (COS/IUI) often face the risk of
      premature luteinization, which may result in lower pregnancy rate and higher
      miscarriage rate. This review was performed to identify if adjuvant treatment
      with GnRH antagonist (GnRH-ant) could effectively improve the clinical outcome of
      patients with PCOS undergoing COS/IUI. A literature search was conducted on the
      PubMed, EMBASE and Cochrane library databases. Two randomized controlled trials
      were included in this review, enrolling a total of 333 cycles. The patients who
      received GnRH-ant treatment had lower progesterone levels on the hCG day and a
      reduced premature luteinization rate. However, the rates of live birth, clinical
      pregnancy and miscarriage did not significantly differ between the GnRH-ant
      supplementation group and control group. In conclusion, although the existing
      randomized controlled trials indicate that GnRH-ant can effectively decrease the
      premature luteinizaton rate, evidence to support its use to improve clinical
      pregnancy outcomes in PCOS patients undergoing COS/IUI treatment is insufficient.

PMID- 24299150
TI  - The 1918 influenza pandemic in New York City: age-specific timing, mortality, and
      transmission dynamics.
AB  - BACKGROUND: The 1918 influenza pandemic caused disproportionately high mortality
      among certain age groups. The mechanisms underlying these differences are not
      fully understood. OBJECTIVES: To explore the dynamics of the 1918 pandemic and to
      identify potential age-specific transmission patterns. METHODS: We examined 1915
      1923 daily mortality data in New York City (NYC) and estimated the outbreak
      duration and initial effective reproductive number (Re ) for each 1-year age
      cohort. RESULTS: Four pandemic waves occurred from February 1918 to April 1920.
      The fractional mortality increase (i.e. ratio of excess mortality to baseline
      mortality) was highest among teenagers during the first wave. This peak shifted
      to 25- to 29-year-olds in subsequent waves. The distribution of age-specific
      mortality during the last three waves was strongly correlated (r = 0.94 and
      0.86). With each wave, the pandemic appeared to spread with a comparable early
      growth rate but then attenuate with varying rates. For the entire population, Re
      estimates made assuming 2-day serial interval were 1.74 (1.27), 1.74 (1.43), 1.66
      (1.25), and 1.86 (1.37), respectively, during the first week (first 3 weeks) of
      each wave. Using age-specific mortality, the average Re estimates over the first
      week of each wave were 1.62 (95% CI: 1.55-1.68), 1.68 (1.65-1.72), 1.67 (1.61
      1.73), and 1.69 (1.63-1.74), respectively; Re was not significantly different
      either among age cohorts or between waves. CONCLUSIONS: The pandemic generally
      caused higher mortality among young adults and might have spread mainly among
      school-aged children during the first wave. We propose mechanisms to explain the
      timing and transmission dynamics of the four NYC pandemic waves.

PMID- 24299152
TI  - Contact activation products are new potential biomarkers to evaluate the risk of
      thrombotic events in systemic lupus erythematosus.
AB  - INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have persistent
      platelet activation and an increased risk of thrombotic events, which cannot be
      accounted for by traditional cardiovascular risk factors. Factor (F)XII has a
      potentially important role in thrombus formation and is triggered by activated
      platelets. We therefore asked whether the contact system is involved in
      inflammation and vascular disease (VD) in SLE. METHODS: Fibrin clots were
      incubated with purified FXII or whole blood, and the activation and regulation of
      FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38)
      previous VD and from matched healthy controls (n = 68) were analyzed for the
      presence of complexes formed between contact system enzymes and antithrombin (AT)
      or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory
      parameters. RESULTS: Fibrin clots elicited FXII activation and acted as co
      factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa
      C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa
      AT was elevated in the SLE patients with a history of VD, while the corresponding
      levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated
      strongly with platelet parameters. The odds ratio for VD among the SLE patients
      was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of
      FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa
      C1INH and increased levels of FXIIa-AT. CONCLUSIONS: Activation of FXII is
      elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin
      acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered
      levels of FXIIa-serpin complexes, supporting that the contact system is involved
      in this disease. FXIIa-serpin complexes are strongly associated with previous VD
      in SLE patients, suggesting that these complexes are potential biomarkers for
      monitoring and assessing the risk of thrombotic events in SLE.

PMID- 24299153
TI  - The importance of free fatty acid chain length for the skin barrier function in
      atopic eczema patients.
AB  - An important feature of atopic eczema (AE) is a decreased skin barrier function.
      The stratum corneum (SC) lipids - comprised of ceramides (CERs), free fatty acids
      (FFAs) and cholesterol - fulfil a predominant role in the skin barrier function.
      In this clinical study, the carbon chain length distribution of SC lipids (FFAs
      and CERs) and their importance for the lipid organization and skin barrier
      function were examined in AE patients and compared with control subjects. A
      reduction in FFA chain length and an increase in unsaturated FFAs are observed in
      non-lesional and lesional SC of AE patients. The reduction in FFA chain length
      associates with a reduced CER chain length, suggesting a common synthetic
      pathway. The lipid chain length reduction correlates with a less dense lipid
      organization and a decreased skin barrier function. All changes are more
      pronounced in lesional SC compared with non-lesional skin. No association was
      observed between lipid properties and filaggrin mutations, an important
      predisposing factor for developing AE. The results of this study demonstrate an
      altered SC lipid composition and signify the importance of these changes
      (specifically regarding the CER and FFA chain lengths) for the impaired skin
      barrier function in AE. This provides insights into epidermal lipid metabolism as
      well as new opportunities for skin barrier repair. 

PMID- 24299154
TI  - Evaluating PET-CT in the detection and management of recurrent cervical cancer:
      systematic reviews of diagnostic accuracy and subjective elicitation.
AB  - BACKGROUND: Positron emission tomography-computed tomography (PET-CT) is
      recommended to triage women for exenterative surgery and surveillance after
      treatment for advanced cervical cancer. OBJECTIVE: To evaluate diagnostic
      accuracy of additional whole body PET-CT compared with CT/magnetic resonance
      imaging (MRI) alone in women with suspected recurrent/persistent cervical cancer
      and in asymptomatic women as surveillance. DESIGN: Systematic reviews. Subjective
      elicitation to supplement diagnostic information. SEARCH STRATEGY/SELECTION
      CRITERIA/DATA COLLECTION AND ANALYSIS: Searches of electronic databases were
      performed to June 2013. Studies in women with suspected recurrent/persistent
      cervical cancer and in asymptomatic women undergoing follow up with sufficient
      numeric data were included. We calculated sensitivity, specificity and
      corresponding 95% confidence intervals. Meta-analyses employed a bivariate model
      that included a random-effects term for between-study variations (CT studies) and
      univariate random effects meta-analyses (PET-CT studies) for sensitivity and
      specificity separately. SUBJECTIVE ELICITATION: Prevalence of recurrence and the
      accuracy of imaging elicited using the allocation of points technique. Coherence
      of elicited subjective probabilities with estimates in the literature examined.
      RESULTS: We identified 15 relevant studies; none directly compared additional PET
      CT with MRI or CT separately. Most CT and MRI studies used older protocols and
      the majority did not distinguish between asymptomatic and symptomatic women. Meta
      analysis of nine PET-CT studies in mostly symptomatic women showed sensitivity of
      94.8 (95% CI 91.2-96.9), and specificity of 86.9% (95% CI 82.2-90.5). The summary
      estimate of the sensitivity of CT for detection of recurrence was 89.64% (95% CI
      81.59-94.41) and specificity was 76% (95% CI 43.68-92.82). Meta-analysis for MRI
      test accuracy studies was not possible because of clinical heterogeneity. The
      sensitivity and specificity of MRI in pelvic recurrence varied between 82 and
      100% and between 78 and 100%, respectively. Formal statistical comparisons of the
      accuracy of index tests were not possible. Subjective elicitation provided
      estimates comparable to the literature. Subjective estimates of the increase in
      accuracy from the addition of PET-CT were less than elicited increases required
      to justify the use in PET-CT for surveillance. CONCLUSION: Evidence to support
      additional PET-CT is scarce, of average quality and does not distinguish between
      application for surveillance and diagnosis. Guidelines recommending PET-CT in
      recurrent cervical cancer need to be reconsidered in the light of the existing
      evidence base.

PMID- 24299155
TI  - Medicinal compounds with antiepileptic/anticonvulsant activities.
AB  - OBJECTIVE: Epilepsy is a serious neural disease that affects around 50 million
      people all over the world. Although for the majority patients with epilepsy,
      seizures are well controlled by currently available antiepileptic drugs (AEDs),
      there are still >30% of patients suffered from medically refractory epilepsy and
      approximately 30-40% of all epileptic patients affected by numerous side effects
      and seizure resistance to the current AEDs. Therefore, many researchers try to
      develop novel approaches to treat epilepsy, for example, to discover new
      antiepileptic constituents from herbal medicines. Although there are already
      several reviews on phytotherapy in epilepsy, most of them placed emphasis on the
      plant crude extracts or their isolated fractions, not pure active compounds
      derived from herbal medicines. This article aims to review components in herbal
      medicines that have shown antiepileptic or anticonvulsant properties. METHODS: We
      searched online databases and identified articles using the preset searching
      syntax and inclusion criteria. The active medicinal compounds that have shown
      anticonvulsant or antiepileptic activity were included and classified according
      to structural types. RESULTS: We have reviewed herein the active constituents
      including alkaloids, flavonoids, terpenoids, saponins, and coumarins. The
      screening models, the seizures-inducing factors and response, the effective dose,
      the potential mechanisms, as well as the structure-activity relationships in some
      of these active components have also been discussed. SIGNIFICANCE: The in vitro
      and in vivo experimental data reviewed in this paper would supply the basic
      science evidence for research and development of novel AEDs from medicinal
      plants.

PMID- 24299157
TI  - From sequential to one-pot synthesis of dipyrrin based grid-type mixed metal
      organic frameworks.
AB  - Both sequential and one-pot strategies for the preparation of a series of grid
      type mixed metal-organic frameworks (MM'MOFs) based on dipyrrin ligands appended
      with either a pyridyl or a phenyl-imidazolyl moiety have been investigated. For
      the stepwise approach, the differentiation between the two coordination sites
      (nature, charge, and denticity) was exploited for the synthesis of a family of
      five discrete Zn(II), Cu(II), and Pd(II) complexes. Acting as metallatectons,
      these construction building blocks lead to the formation of a series of MM'MOFs
      upon self-assembly with CdCl2. In these rhombic grid-type architectures, four
      consecutive metallatectons are bridged by Cd(II) cations adopting an octahedral
      coordination geometry with the chloride anions occupying apical positions, thus
      behaving as square nodes. The shape of the rhombus grids as well as the way they
      are packed (stacking or interpenetration) in the crystalline phase are controlled
      by the nature of metallatectons and the solvent molecules present in the
      crystals. Consequently, the heterometallic assemblies display different
      accessible voids, although they are built on layers with the same connectivity.
      More interestingly, as demonstrated by X-ray diffraction on both single crystals
      and microcrystalline powders, the same MM'MOFs were obtained by a one-pot
      strategy through direct combinations of dipyrrin derivatives with the
      corresponding metal salts. This one-pot approach is efficient and more convenient
      than the sequential alternative, since the isolation, purification, and
      characterization of the, sometimes insoluble, metallatectons are not required. 

PMID- 24299156
TI  - HNF4A mutation: switch from hyperinsulinaemic hypoglycaemia to maturity-onset
      diabetes of the young, and incretin response.
AB  - BACKGROUND: Hepatocyte nuclear factor 4alpha (HNF4A) is a member of the nuclear
      receptor family of ligand-activated transcription factors. HNF4A mutations cause
      hyperinsulinaemic hypoglycaemia in early life and maturity-onset diabetes of the
      young. Regular screening of HNF4A mutation carriers using the oral glucose
      tolerance test has been recommended to diagnose diabetes mellitus at an early
      stage. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide
      are incretin hormones, responsible for up to 70% of the secreted insulin after a
      meal in healthy individuals. We describe, for the first time, gradual alteration
      of glucose homeostasis in a patient with HNF4A mutation after resolution of
      hyperinsulinaemic hypoglycaemia, on serial oral glucose tolerance testing. We
      also measured the incretin response to a mixed meal in our patient. CASE REPORT:
      Our patient was born with macrosomia and developed hyperinsulinaemic
      hypoglycaemia in the neonatal period. Molecular genetic analysis confirmed HNF4A
      mutation (p.M116I, c.317G>A) as an underlying cause of hyperinsulinaemic
      hypoglycaemia. Serial oral glucose tolerance testing, after the resolution of
      hyperinsulinaemic hypoglycaemia, confirmed the diagnosis of maturity-onset
      diabetes of the young at the age of 10 years. Interestingly, the intravenous
      glucose tolerance test revealed normal glucose disappearance rate and first-phase
      insulin secretion. Incretin hormones showed a suboptimal rise in response to the
      mixed meal, potentially explaining the discrepancy between the oral glucose
      tolerance test and the intravenous glucose tolerance test. CONCLUSIONS: Maturity
      onset diabetes of the young can develop as early as the first decade of life in
      persons with an HNF4A mutation. Impaired incretin response might be contributory
      in the early stages of HNF4A maturity-onset diabetes of the young.

PMID- 24299158
TI  - Phytoestrogens induce apoptosis through a mitochondria/caspase pathway in human
      breast cancer cells.
AB  - OBJECTIVE: To explore the effect and pathway of phytoestrogens on the growth of
      breast cancer cell line MCF-7. METHODS: MCF-7 cells (human estrogen receptor
      positive and progesterone receptor-positive breast cancer cells) were cultured in
      serum-free medium for 24 h and then treated with genistein, resveratrol, and
      quercetin (10(-10)-10(-4) mol/l). After further incubation for 24, 48, 72, and 92
      h, the cells were harvested and extracted for 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. According to the above results, the
      proteins involving proliferative and apoptotic pathways were evaluated by Western
      blot analysis. RESULTS: Genistein, resveratrol, and quercetin significantly
      inhibited cellular proliferation in a dose- and time-dependent manner.
      Significantly elevated caspase-3 activity was noted after treatment with
      genistein (10(-9)-10(-7) mol/l), as well as with resveratrol and quercetin (10(
      9)-10(-5) mol/l). Significant reduction of PI3K and AKT protein and significant
      increase of Fas ligand, Fas-associated protein with death domain, cytochrome C,
      truncated Bid, caspase-9, and caspase-3 were all noted after genistein,
      resveratrol, and quercetin treatment. 17beta-Estradiol induced completely
      opposite results. Estrogen receptor (ER) alpha expression was significantly
      increased with 17beta-estradiol, whereas ERbeta expression was significantly
      elevated in the cultures with genistein, resveratrol, and quercetin. CONCLUSIONS:
      These data demonstrate that genistein, resveratrol, and quercetin have
      antiproliferative effects on breast cancer cells. Their induction of apoptosis
      involves the activation of both the intrinsic and extrinsic apoptotic pathways,
      which may be related to the differential affinity to ERalpha and ERbeta. Whether
      phytoestrogens have similar effects on normal breast cells remains to be
      examined.

PMID- 24299159
TI  - The role of Violence Against Women Act in addressing intimate partner violence: a
      public health issue.
AB  - Intimate partner violence (IPV) is defined as violence committed by a current or
      former boyfriend or girlfriend, spouse or ex-spouse. Each year, 1.3 to 5.3
      million women in the United States experience IPV. The large number of
      individuals affected, the enormous healthcare costs, and the need for a
      multidisciplinary approach make IPV an important healthcare issue. The Violence
      Against Women Act (VAWA) addresses domestic violence, dating violence, sexual
      assault, and stalking. It emphasizes development of coordinated community care
      among law enforcement, prosecutors, victim services, and attorneys. VAWA was not
      reauthorized in 2012 because it lacked bipartisan support. VAWA 2013 contains
      much needed new provisions for Native Americans; lesbian, gay, bisexual,
      transgender, gay, and queer (LGBTQ) individuals; and victims of human trafficking
      but does not address the large amount of intimate partner violence in America's
      immigrant population. There are important remaining issues regarding intimate
      partner violence that need to be addressed by future legislation. This review
      examines the role of legislation and addresses proposals for helping victims of
      IPV.

PMID- 24299160
TI  - Predictors of improvement in endothelial function after exercise training in a
      diverse sample of postmenopausal women.
AB  - BACKGROUND: Endothelial dysfunction measured via flow-mediated dilation (FMD) is
      associated with greater risk of future hypertension and cardiovascular events in
      postmenopausal women. Aerobic exercise training has been shown to improve
      endothelial function in Caucasian populations, but has not been evaluated
      specifically in African Americans. This has clinical importance due to the
      increased prevalence of cardiovascular disease in African Americans. METHODS: In
      the present pilot study, 8 African American (age: 55.8+/-1.7 years, peak oxygen
      uptake [VO2 peak]: 21.0+/-3.9 mL/kg/minute, body mass index [BMI]: 30.1+/- 6.3
      kg/m(2)) and 16 Caucasian (age: 57.2+/-5.9 years, VO2 peak: 21.8+/-3.7
      mL/kg/minute, BMI: 29.3+/-5.2 kg/m(2)) sedentary postmenopausal women underwent
      brachial artery FMD measurements before and after 12 weeks of aerobic exercise
      training. FMD was quantified by comparing B-mode ultrasound images of the
      brachial artery at rest and following reactive hyperemia after 5 minutes of
      forearm occlusion. Participants performed aerobic exercise training 4 days per
      week for 12 weeks. RESULTS: Despite improvements in fitness in both groups,
      aerobic exercise training did not significantly improve FMD in African American
      (5.8% to 5.7%, p=0.950) or Caucasian postmenopausal women (5.7% to 6.6%,
      p=0.267). In women with the greatest impairment in endothelial function at
      baseline (FMD<4.5%), a significant improvement in FMD was observed, independent
      of race, following exercise training (2.2% to 6.2%, p=0.007). CONCLUSION: The
      benefits of aerobic exercise training on endothelial function in postmenopausal
      women are most pronounced in women with endothelial dysfunction prior to training
      and do not appear to be affected by race.

PMID- 24299162
TI  - Permanent stoma rates: a misleading marker of quality in rectal cancer surgery.
AB  - AIM: The latest National Bowel Cancer Audit Programme (NBOCAP) audit identified
      our colorectal unit as an outlier with regard to the high permanent stoma rate.
      The aim of this study was to perform an audit of the rationale for stoma
      formation in patients undergoing rectal cancer resection in our unit. METHOD: A
      review was conducted of all rectal cancer operations between April 2011 and March
      2013. Preoperative staging investigations and operation reports were reviewed to
      identify the reasons for nonrestorative surgery. Postoperative histology reports
      were used to identify circumferential resection margin (CRM) involvement and
      tumour height. RESULTS: One-hundred and twenty-five patients underwent surgery
      for rectal cancer, of whom 102 underwent elective resection with curative intent.
      The permanent stoma rate was 63.2% when emergency and palliative procedures were
      included and 54.9% when only elective curative cases were considered. Tertiary
      referrals made up 31.4% of elective cases. The main reasons for nonrestorative
      surgery included multivisceral resection (n = 24) for locally advanced cancer and
      operations for lesions close to the anal sphincter (n = 21). The median length of
      stay was 8 days, the 90-day mortality was 2.9% and the rate of CRM involvement
      was 2.0%. CONCLUSION: Our unit provides multivisceral surgery for locally
      advanced rectal cancer and receives a substantial number of tertiary referrals.
      Many of the rectal cancers referred are locally advanced or threaten the anal
      sphincter. This study demonstrates that the complexity of a unit's case-mix can
      have a profound effect on the permanent stoma rate. Stoma rates taken at face
      value do not therefore provide an accurate representation of surgical quality.
      What does this paper add to the literature? The study reviews the practice of a
      colorectal surgical unit with an interest in multivisceral surgery with regard to
      the permanent stoma rate. The reasons for nonrestorative surgery are analysed,
      and the problems associated with the use of stoma rates as a marker of quality in
      colorectal surgery are highlighted.

PMID- 24299163
TI  - Triphenylphosphinecarboxamide: an effective reagent for the reduction of azides
      and its application to nucleic acid detection.
AB  - A series of triphenylphosphinecarboxamide (TPPc) derivatives were designed and
      synthesized as alternative reagents to triphenylphosphine for the facile
      reduction of azides. The TPPc derivatives performed as efficient reducing agents
      for the synthesis of primary amines without the need for an additional hydrolysis
      procedure. The TPPc derivatives were also applied to nucleic acid sensing using a
      RhAz-oligonucleotide conjugate in a DNA-templated fluorogenic reaction. 

PMID- 24299161
TI  - Transcriptome analysis of the filamentous fungus Aspergillus nidulans directed to
      the global identification of promoters.
AB  - BACKGROUND: The filamentous fungus Aspergillus nidulans has been a tractable
      model organism for cell biology and genetics for over 60 years. It is among a
      large number of Aspergilli whose genomes have been sequenced since 2005,
      including medically and industrially important species. In order to advance our
      knowledge of its biology and increase its utility as a genetic model by improving
      gene annotation we sequenced the transcriptome of A. nidulans with a focus on 5'
      end analysis. RESULTS: Strand-specific whole transcriptome sequencing showed that
      80-95% of annotated genes appear to be expressed across the conditions tested. We
      estimate that the total gene number should be increased by approximately 1000, to
      11,800. With respect to splicing 8.3% of genes had multiple alternative
      transcripts, but alternative splicing by exon-skipping was very rare. 75% of
      annotated genes showed some level of antisense transcription and for one gene,
      meaB, we demonstrated the antisense transcript has a regulatory role. Specific
      sequencing of the 5' ends of transcripts was used for genome wide mapping of
      transcription start sites, allowing us to interrogate over 7000 promoters and 5'
      untranslated regions. CONCLUSIONS: Our data has revealed the complexity of the A.
      nidulans transcriptome and contributed to improved genome annotation. The data
      can be viewed on the AspGD genome browser.

PMID- 24299164
TI  - Challenges in diabetes management in Indonesia: a literature review.
AB  - BACKGROUND AND OBJECTIVES: The expanding diabetes epidemic worldwide could have
      potentially devastating effects on the development of healthcare systems and
      economies in emerging countries, both in terms of direct health care costs and
      loss of working time and disability. This study aims to review evidence on the
      burden, expenditure, complications, treatment, and outcomes of diabetes in
      Indonesia and its implications on the current health system developments.
      METHODS: We conducted a comprehensive literature review together with a review of
      unpublished data from the Ministry of Health and a public health insurer (Askes).
      Studies presenting evidence on prevalence, incidence, mortality, costs,
      complications and cost of complications, treatment, and outcomes were included in
      the analysis. RESULTS: A limited number of international, national and local
      studies on the burden and cost of diabetes in Indonesia were identified. National
      survey data suggests that in 2007 the prevalence of diabetes was 5.7%, of which
      more than 70% of cases were undiagnosed. This estimate hides large intracountry
      variation. There was very limited data available on direct costs and no data on
      indirect costs. The most commonly-identified complication was diabetic
      neuropathy. DISCUSSION: There were a number of limitations in the data retrieved
      including the paucity of data representative at the national level, lack of a
      clear reference date, lack of data from primary care, and lack of data from
      certain regions of the country. CONCLUSIONS: If left unaddressed, the growing
      prevalence of diabetes in the country will pose a tremendous challenge to the
      Indonesian healthcare system, particularly in view of the Government's 2010
      mandate to achieve universal health coverage by 2014. Essential steps to address
      this issue would include: placing diabetes and non-communicable diseases high on
      the Government agenda and creating a national plan; identifying disparities and
      priority areas for Indonesia; developing a framework for coordinated actions
      between all relevant stakeholders.

PMID- 24299165
TI  - Strontium randomly substituting for calcium in fish otolith aragonite.
AB  - The chemistry of fish ear bones (otoliths) is used to address fundamental
      questions in fish ecology and fisheries science. It is assumed that strontium
      (Sr), the most important element used in otolith chemistry research, is bound
      within the aragonitic calcium carbonate lattice of otoliths via random chemical
      replacement of calcium; however, this has never been tested and three other
      alternatives exist with regard to how Sr may be incorporated. If any variation in
      the mode of incorporation occurs, otolith chemistry data may be misinterpreted,
      impacting how fish and fisheries are understood and managed. Using X-ray
      absorption spectroscopy (specifically, analysis of extended X-ray absorption fine
      structure or EXAFS), we investigated how Sr is incorporated within fish otoliths
      from seven species collected from a range of aquatic environments. For
      comparison, aragonitic structures from other aquatic taxa (cephalopods and coral)
      were also analyzed. The results consistently indicated for all samples that Sr
      randomly replaces Ca within the aragonite lattice. This research explicitly shows
      how Sr is bound within otoliths and validates a fundamental and long-held
      assumption in aquatic research. 

PMID- 24299166
TI  - A universe of dwarfs and giants: genome size and chromosome evolution in the
      monocot family Melanthiaceae.
AB  - * Since the occurrence of giant genomes in angiosperms is restricted to just a
      few lineages, identifying where shifts towards genome obesity have occurred is
      essential for understanding the evolutionary mechanisms triggering this process.
      * Genome sizes were assessed using flow cytometry in 79 species and new
      chromosome numbers were obtained. Phylogenetically based statistical methods were
      applied to infer ancestral character reconstructions of chromosome numbers and
      nuclear DNA contents. * Melanthiaceae are the most diverse family in terms of
      genome size, with C-values ranging more than 230-fold. Our data confirmed that
      giant genomes are restricted to tribe Parideae, with most extant species in the
      family characterized by small genomes. Ancestral genome size reconstruction
      revealed that the most recent common ancestor (MRCA) for the family had a
      relatively small genome (1C = 5.37 pg). Chromosome losses and polyploidy are
      recovered as the main evolutionary mechanisms generating chromosome number
      change. * Genome evolution in Melanthiaceae has been characterized by a trend
      towards genome size reduction, with just one episode of dramatic DNA accumulation
      in Parideae. Such extreme contrasting profiles of genome size evolution
      illustrate the key role of transposable elements and chromosome rearrangements in
      driving the evolution of plant genomes.

PMID- 24299167
TI  - Hunting down the chimera of multiple disciplinarity in conservation science.
AB  - The consensus is that both ecological and social factors are essential dimensions
      of conservation research and practice. However, much of the literature on
      multiple disciplinary collaboration focuses on the difficulties of undertaking
      it. This review of the challenges of conducting multiple disciplinary
      collaboration offers a framework for thinking about the diversity and complexity
      of this endeavor. We focused on conceptual challenges, of which 5 main categories
      emerged: methodological challenges, value judgments, theories of knowledge,
      disciplinary prejudices, and interdisciplinary communication. The major problems
      identified in these areas have proved remarkably persistent in the literature
      surveyed (c.1960-2012). Reasons for these failures to learn from past experience
      include the pressure to produce positive outcomes and gloss over disagreements,
      the ephemeral nature of many such projects and resulting lack of institutional
      memory, and the apparent complexity and incoherence of the endeavor. We suggest
      that multiple disciplinary collaboration requires conceptual integration among
      carefully selected multiple disciplinary team members united in investigating a
      shared problem or question. We outline a 9-point sequence of steps for setting up
      a successful multiple disciplinary project. This encompasses points on
      recruitment, involving stakeholders, developing research questions, negotiating
      power dynamics and hidden values and conceptual differences, explaining and
      choosing appropriate methods, developing a shared language, facilitating on-going
      communications, and discussing data integration and project outcomes. Although
      numerous solutions to the challenges of multiple disciplinary research have been
      proposed, lessons learned are often lost when projects end or experienced
      individuals move on. We urge multiple disciplinary teams to capture the
      challenges recognized, and solutions proposed, by their researchers while
      projects are in process. A database of well-documented case studies would
      showcase theories and methods from a variety of disciplines and their
      interactions, enable better comparative study and evaluation, and provide a
      useful resource for developing future projects and training multiple disciplinary
      researchers.

PMID- 24299168
TI  - Characteristics of Jordanian depressed pregnant women: a comparison study.
AB  - The objective of this study is to investigate the differences between Jordanian
      depressed women and non-depressed women in terms of their sociodemographic
      characteristics during their pregnancy. A convenience sample of 218 Jordanian
      pregnant women in their third trimester was selected for this study from three
      major Governorates in Jordan (Amman, Irbid and Zarqa), and the antenatal clinics
      of teaching hospitals (Jordan University Hospital and King Abdullah University
      Hospital) were accessed to collect the data. A demographical sheet and the
      Edinburgh Postnatal Depression Scale (EPDS) were used to collect data. There was
      a significant difference in EPDS scores between smokers and non-smokers,
      primiparous and multiparous women, and also between women with secondary or lower
      education and those with diploma or higher education. Higher EPDS scores were
      classified as a >=13 and lower EPDS scores as <13. However, there were no
      significant differences in the age, income and sleeping hours for women with
      higher EPDS scores compared with those with lower EPDS scores. This study showed
      that there are differences between pregnant women who had depression symptoms and
      pregnant women who did not have depression symptoms in relation to some
      sociodemographic variables (smoking status, education level and parity).

PMID- 24299170
TI  - Information needs of cancer patients and survivors regarding diet, exercise and
      weight management: a qualitative study.
AB  - While advanced cancer is often associated with weight loss, curative cancer
      treatment is often associated with weight gain. Weight gain during treatment may
      be associated with greater risk of cancer recurrence and development of lifestyle
      diseases. Currently, limited resources are available to cancer patients focussed
      on weight control. This study assessed the information needs of patients
      undergoing curative chemotherapy regarding diet, exercise and weight management
      for the purpose of developing weight management resources. Focus groups were held
      with oncology practitioners, patients and survivors to determine current
      information provision and needs. Focus groups highlighted a perception that
      information provision regarding diet, exercise and weight management is
      insufficient and no routine assessment of weight occurs during chemotherapy.
      Barriers to information provision described included lack of resources and time,
      and practitioners' uncertainty regarding appropriate messages to provide.
      Patients wanted more information regarding diet, exercise and weight during
      treatment time. The findings of this study suggest an increase in provision of
      diet, exercise and weight management information is needed. This information
      should be evidence-based and delivered at an appropriate time by the preferred
      health care professional. It would also be beneficial to implement protocols
      regarding assessment of weight during treatment. 

PMID- 24299171
TI  - Improved pyroelectric figures of merit in compositionally graded PbZr1-xTixO3
      thin films.
AB  - Pyroelectric materials have been widely used for a range of thermal-related
      applications including thermal imaging/sensing, waste heat energy conversion, and
      electron emission. In general, the figures of merit for applications of
      pyroelectric materials are proportional to the pyroelectric coefficient and
      inversely proportional to the dielectric permittivity. In this context, we
      explore single-layer and compositionally graded PbZr1-xTixO3 thin-film
      heterostructures as a way to independently engineer the pyroelectric coefficient
      and dielectric permittivity of materials and increase overall performance.
      Compositional gradients in thin films are found to produce large strain gradients
      which generate large built-in potentials in the films that can reduce the
      permittivity while maintaining large pyroelectric response. Routes to enhance the
      figures of merit of pyroelectric materials by 3-12 times are reported, and
      comparisons to standard materials are made. 

PMID- 24299169
TI  - Abnormal semantic processing in females with fragile X-associated tremor/ataxia
      syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative
      disorder, affects fragile X (FMR1) gene premutation carriers in late life.
      Studies have shown cognitive impairments in FXTAS including executive
      dysfunction, working memory and visuospatial deficits. However, less is known
      about cognition in females with FXTAS. Thus, we examined semantic processing and
      verbal memory in female FXTAS patients with event-related potentials (ERPs) and
      neuropsychological testing. Sixty-one females (34 FXTAS, Mage  = 62.7; 27
      controls, Mage  = 60.4) were studied with 32-channel ERPs during a category
      judgment task in which semantically congruous (50%) and incongruous items were
      repeated approximately 10-140 seconds later. N400 and P600 amplitude data were
      submitted to analysis of covariance. Neuropsychological testing demonstrated
      lower performance in verbal learning and executive function in females with
      FXTAS. Event-related potential analyses showed a significant reduction of the
      N400 congruity effect (incongruous - congruous) in the FXTAS group. The N400
      congruity effect reduction in females with FXTAS was mainly due to increased N400
      amplitude to congruous new words. No significant abnormalities of the N400
      repetition effect or the P600 repetition effect were found, indicating preserved
      implicit memory and verbal memory, respectively, in females with FXTAS. The
      decreased N400 congruity effect suggests abnormal semantic expectancy and/or
      semantic network disorganization in female FXTAS patients. The enhanced N400
      amplitude to congruous new words may reflect decreased cognitive flexibility
      among FXTAS women, making access to less typical category exemplar words more
      difficult. 

PMID- 24299172
TI  - Self-face recognition in the ultra-high risk for psychosis population.
AB  - AIM: Phenomenological research indicates that disturbance of the basic sense of
      self may be a core phenotypic marker of schizophrenia spectrum disorders. Self
      face recognition (SFR) is an experimental paradigm which can assess the basic
      sense of self. In this study, we used SFR to determine whether basic self
      disturbance is present in the ultra-high risk (UHR) for psychosis population at
      the perceptual level. METHODS: Twenty-three UHR individuals and 23 healthy
      comparison subjects were administered the SFR task. The study consisted of a 2 *
      3 * 2 design: two group levels (UHR for psychosis group and the healthy
      comparison group); three task levels (self-famous task, self-stranger task,
      famous-stranger task); and two hand levels (left hand and right hand). Threshold
      limit values in face recognition were analysed. RESULTS: The analysis indicated
      effects for group (F(1, 43) = 5.197, P < 0.05) and interaction effects between
      group and task (F = 4.767, P < 0.05). An independent samples t-test was used to
      compare the threshold limit values of the same task between the two groups. For
      self-famous task, the threshold limit values of the UHR group were higher than
      those of healthy group both in the left and right hands (t = 2.734, P < 0.05; t =
      2.864, P < 0.05), but no significant difference was found in self-stranger task
      and famous-stranger task (P > 0.05). CONCLUSIONS: This SFR study indicates that
      basic self-disturbance is present in the UHR for psychosis at the behavioural
      level in comparison with a healthy comparison group.

PMID- 24299174
TI  - Electrophilic aromatic substitution: enthalpies of hydrogenation of the ring
      determine reactivities of C6H5X. The direction of the C6H5-X bond dipole
      determines orientation of the substitution.
AB  - There are still some secrets left to this well-studied reaction. Previously
      unreported relationships discovered are as follows. The ordering of reactivities
      of C6H5X is the same as that of enthalpies of hydrogenation of the ring to the
      correspondingly substituted cyclohexane. The orientation of substitution (meta or
      ortho/para) is controlled by the dipole direction of the ipso-C-X bond, like an
      ON/OFF switch. The difference between the halogens and other deactivating groups
      is that the bond between the atom bonded to the ipso carbon has the positive end
      of the dipole on the ipso carbon for the halogens (C(delta+)-X(delta-)) but in
      the opposite direction (C(delta-)-X(delta+)) for other deactivating groups. This
      reverses the directing effect. For all X, including the halogens, ipso-C(delta+)
      X(delta-) results in ortho/para substitution. p-(13)C NMR shifts of C6H5X greater
      than that of benzene predict meta substitution. A linear relationship exists
      between p-(13)C NMR shift and DeltaHhyd, except for X = halogen. With
      halobenzenes, the ortho/para ratios of the products are linearly related to the
      ipso/ortho ratios of the (13)C shifts of C6H5X for chlorinations, brominations,
      nitrations, and protonations. The relative reactivities of the halobenzenes are
      linearly related to the p-(13)C NMR shifts. The electronegativities of X are
      linearly related to the (13)C NMR shifts of the ipso carbon. 

PMID- 24299173
TI  - Clinical characteristics of patients with treated epilepsy in Korea: a nationwide
      epidemiologic study.
AB  - OBJECTIVE: Although a number of epidemiologic studies have been conducted on the
      prevalence and incidence of epilepsy around the world, only a few studies have
      investigated the clinical characteristics of patients with epilepsy in a
      population-based sample. The purpose of the present study was to describe the
      clinical characteristics of treated patients with epilepsy in Korea via a
      nationwide medical records survey. METHODS: The study population was obtained
      through a nationwide database registered to the Health Insurance Review and
      Assessment service. Patients were recruited from clinics and hospitals in each
      cluster according to region and referral level by random selection from a
      preallocated sample of patients. All patients were being treated with
      antiepileptic drug medication with or without a diagnosis code for epilepsy or
      seizure between January 2009 and December 2009. Among the 6,436 selected
      patients, 2,150 met the diagnostic criteria for epilepsy and were included in our
      survey on the clinical characteristics of patients who were with treated
      epilepsy. RESULTS: The proportion of male patients with epilepsy in this study
      was higher (1,226; 57.0%) than that of female patients. In addition, 10.6% of
      patients were first diagnosed with epilepsy in 2009, and 53.6% of patients
      experienced at least one seizure over the course of 2009; 78.1% were classified
      as having localization-related epilepsy, whereas 7.3% were considered to have
      generalized epilepsy. Thirty-five percent of patients were thus classified as
      idiopathic or cryptogenic cases. The most common cause of symptomatic epilepsy
      was trauma (10.0%), followed by stroke (9.6%), central nervous system (CNS)
      infection (5.7%), and hippocampal sclerosis (4.9%). SIGNIFICANCE: This is the
      first nationwide study of the clinical characteristics of treated epilepsy in
      Korea using a national database validated by medical records survey. The
      etiologies of epilepsy and epilepsy syndrome classifications were comparable to
      those previously reported in other developed countries.

PMID- 24299176
TI  - Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the
      market in the last decade (2001-2011).

PMID- 24299175
TI  - PDL241, a novel humanized monoclonal antibody, reveals CD319 as a therapeutic
      target for rheumatoid arthritis.
AB  - INTRODUCTION: Targeting the CD20 antigen has been a successful therapeutic
      intervention in the treatment of rheumatoid arthritis (RA). However, in some
      patients with an inadequate response to anti-CD20 therapy, a persistence of CD20-
      plasmablasts is noted. The strong expression of CD319 on CD20- plasmablast and
      plasma cell populations in RA synovium led to the investigation of the potential
      of CD319 as a therapeutic target. METHODS: PDL241, a novel humanized IgG1
      monoclonal antibody (mAb) to CD319, was generated and examined for its ability to
      inhibit immunoglobulin production from plasmablasts and plasma cells generated
      from peripheral blood mononuclear cells (PBMC) in the presence and absence of RA
      synovial fibroblasts (RA-SF). The in vivo activity of PDL241 was determined in a
      human PBMC transfer into NOD scid IL-2 gamma chain knockout (NSG) mouse model.
      Finally, the ability of PDL241 to ameliorate experimental arthritis was evaluated
      in a collagen-induced arthritis (CIA) model in rhesus monkeys. RESULTS: PDL241
      bound to plasmablasts and plasma cells but not naive B cells. Consistent with the
      binding profile, PDL241 inhibited the production of IgM from in vitro PBMC
      cultures by the depletion of CD319+ plasmablasts and plasma cells but not B
      cells. The activity of PDL241 was dependent on an intact Fc portion of the IgG1
      and mediated predominantly by natural killer cells. Inhibition of IgM production
      was also observed in the human PBMC transfer to NSG mouse model. Treatment of
      rhesus monkeys in a CIA model with PDL241 led to a significant inhibition of anti
      collagen IgG and IgM antibodies. A beneficial effect on joint related parameters,
      including bone remodeling, histopathology, and joint swelling was also observed.
      CONCLUSIONS: The activity of PDL241 in both in vitro and in vivo models
      highlights the potential of CD319 as a therapeutic target in RA.

PMID- 24299177
TI  - Intercalation of azamacrocyclic crown ether into layered rare-earth hydroxide
      (LRH): secondary host-guest reaction and efficient heavy metal removal.
AB  - A carboxyethyl substituted azacrown ether (CSAE) derivative was intercalated as a
      second host into a parent host of layered gadolinium hydroxides (LGdH) by an
      anion-exchange reaction. The influence of intercalation temperature and starting
      material ratios of CSAE/LRH on the structures and compositions of CSAE-LRH
      nanocomposites were investigated. Higher temperature and larger initial CSAE-LGdH
      weight ratios favor of higher degree of ion exchange at a certain range, while
      lower temperature gives good morphology for the composites. The adsorptive
      properties for transition and heavy metal ions were studied using the 20  degrees
      C-reacted composite, which showed higher adsorptivity toward transition and heavy
      metal ions, accompanied by the introduction of nitrate anions. The adsorptive
      capacity for transition metal ions was in the sequence of Cu(2+) >
      Zn(2+)~Ni(2+)~Co(2+) with a high selectivity to Cu(2+). For the heavy metal ions
      Ag(+), Hg(2+), Pb(2+), and Cd(2+), the composite showed markedly high selectivity
      for Ag(+) and Hg(2+). When putting Cu(2+), Ag(+), Hg(2+), Pb(2+), and Cd(2+)
      together, Ag(+) and Hg(2+) still have higher adsorptive selectivity over Pb(2+)
      and Cd(2+), and Cu(2+) has also relatively high selectivity but not as high as
      Ag(+) and Hg(2+). The nanocomposites with a second host in the interlayer are one
      promising kind of material because of the synergy of the steric effect of the
      parent host (LRH layer) and the particular characteristics of the secondary host
      (interlayer crown ether anions). 

PMID- 24299178
TI  - Determining obstetric patient safety indicators: the differences in neonatal
      outcome measures between different-sized delivery units.
AB  - OBJECTIVE: To study the differences in neonatal outcome and treatment measures in
      Finnish obstetric units. DESIGN: A registry study with Medical Birth Register
      data. SETTING AND POPULATION: All births (n = 2 94 726) in Finland from 2006 to
      2010 with a focus on term, singleton non-university deliveries. METHODS: All 34
      delivery units were grouped into small (below 1000), mid-sized (1000-2999) and
      large (3000 or more) units, and the adverse outcome rates in neonates were
      compared using logistic regression. MAIN OUTCOME MEASURES: Early neonatal deaths,
      stillbirths, Apgar scores, arterial cord pH, Erb's paralysis, respirator
      treatment, the proportion of post-term deliveries (gestational age beyond 42
      weeks) and the proportion of newborns still hospitalised 7 days after delivery.
      RESULTS: From an analysis of term, singleton non-university deliveries, the early
      neonatal mortality was significantly higher in the small relative to the mid
      sized delivery units [odds ratio (OR), 2.07; 95% confidence interval (CI), 1.19
      3.60]. The rate of Erb's paralysis was lowest in the large units (OR, 0.65; 95%
      CI, 0.50-0.84). The use of a respirator was more than two-fold more common in
      large relative to mid-sized units (OR, 2.38; 95% CI, 2.00-2.83). The proportion
      of post-term deliveries was highest in the large units (OR, 1.36; 95% CI, 1.31
      1.42), where a significantly higher percentage of post-term newborns were still
      hospitalised after 7 days (OR, 1.50; 95% CI, 1.19-1.89). CONCLUSIONS: There are
      significant differences in several neonatal indicators dependent on the hospital
      size. An international consensus is needed on which indicators should be used.

PMID- 24299179
TI  - Silylation-based kinetic resolution of alpha-hydroxy lactones and lactams.
AB  - A silylation-based kinetic resolution has been developed for alpha-hydroxy
      lactones and lactams employing the chiral isothiourea catalyst (-)
      benzotetramisole and triphenylsilyl chloride as the silyl source. The system is
      more selective for lactones than lactams, and selectivity factors up to 100 can
      be achieved utilizing commercially available reagents. 

PMID- 24299180
TI  - A single nucleotide polymorphism in the dopamine receptor D2 gene may be
      informative for resistance to fescue toxicosis in angus-based cattle.
AB  - Fescue toxicosis (FT) reduces beef animal growth and fertility. Animals afflicted
      with FT typically have decreased circulating prolactin concentrations and thicker
      summer hair coats. Preliminary experiments examined the informativeness of a
      novel Dopamine Receptor 2 (DRD2) G/A SNP for resistance to FT. Steers grazed tall
      fescue containing a toxic (E+) or non-toxic (NTE) strain of endophyte. Decreased
      serum prolactin concentrations were observed in GG steers in May compared to AA
      steers when grazing E+ pastures (P < 0.02). In a second study, GG steers had
      decreased prolactin concentrations (P = 0.004) and increased hair coat scores (P
      = 0.01) relative to AA steers when grazing E+ pastures. Allele and genotypic
      frequencies were different (P = 0.016 and 0.026, respectively) between spring
      calving and fall-calving herds grazing E+ pastures, such that the A allele and
      the AA genotype were more prevalent in spring-calving herds, suggesting active
      selection for the A allele. Regardless of calving season, AA heifers tended
      toward fewer days to first calf (733.6 +/- 4.4 d) than did GG heifers (756.6 +/-
      9.2 days; P = 0.055). These results suggest that the DRD2 SNP may have use in
      selecting animals resistant to FT.

PMID- 24299181
TI  - Association of single nucleotide polymorphism of GHSR and TGFB2 genes with growth
      and body composition traits in sire and dam lines of a broiler chicken.
AB  - Growth hormone secretagogue receptor (GHSR) modulates many physiological
      processes by binding to its ligand, as well as transforming growth factor-beta 2
      (TGFB2) regulates cell growth and development in animals and, therefore, are
      candidate genes for performance in chickens. In the current study, single
      nucleotide polymorphisms of GHSR C3286 > T and TGFB2 T(-640) > C were genotyped
      in sire and dam lines of a broiler chicken to evaluate the association with the
      growth and body composition traits. Least squares means analysis showed that the
      GHSR C3286 > T SNP was significantly (P < 0.01) associated with growth (DFI and
      ADG) and body composition traits (AFW and %AFW). In addition, the TGFB2 T(-640) >
      C SNP was associated with ADG (P < 0.05) and DFI and body composition traits (DW,
      LBW, BAKWT, %BMW, %HNDWT and %CW) (P < 0.01). Significant associations of the
      single nucleotide polymorphisms (SNPs) on the traits reported in the present
      study might be the distinct usage of codons in avian, or relating to an enhancer
      element and modulating the expression of the gene in chicken. The data indicated
      that these SNPs could be valuable genetic elements for selection of chickens for
      better performance in the population.

PMID- 24299182
TI  - Cloning, E. coli expression, and characterization of heart lactate dehydrogenase
      B from river buffalo (Bubalus bubalis).
AB  - Lactate dehydrogenase is an enzyme of glycolytic pathway which catalyzes the
      interconversion of pyruvate and lactate. The present study describes cDNA
      cloning, E. coli expression and characterization of lactate dehydrogenase B (LDH
      B) from the heart ventricles of river buffalo (Bubalus bubalis). Total RNA was
      isolated from the heart tissue, a 1005bp cDNA encoding complete polypeptide chain
      of 334 amino acids was generated by reverse transcriptase reaction and analyzed
      for nucleotide sequence. The consensus sequence obtained from both strands has
      shown 84% to 98% homology with that of different mammalian species. The
      attributed gene was cloned, expressed in BL21 (DE3) RIPL Codon Plus strain of E.
      coli using pET21a (+) plasmid. The purified recombinant enzyme displayed a KM
      value of 50 uM for pyruvate, an optimum activity at 35 degrees C and pH 7.0. The
      enzyme was found as a homotetramer of 140 kDa on FPLC based gel-filtration
      column. Molecular weight of a subunit of enzyme as determined by mass
      spectrometric analysis was 36530.21 Da. The present study describes the first
      ever report about the cDNA sequence and characteristics of recombinant LDH-B from
      River buffalo.

PMID- 24299183
TI  - Expression, SNP identification, linkage disequilibrium, and haplotype association
      analysis of the growth suppressor gene ZBED6 in Qinchuan beef cattle.
AB  - Zinc finger, BED-type containing 6 (ZBED6) is a novel transcription factor that
      was identified and shown to act as a repressor of IGF2 transcription in skeletal
      muscle myogenesis and development. The aims of this study were to determine ZBED6
      expression level and examine the association of the ZBED6 polymorphism with
      growth traits in Qinchuan beef cattle. The bovine ZBED6 mRNA was detected in
      eight tissues by quantitative real-time PCR (qPCR), being highly expressed in
      skeletal muscle. Three single nucleotide polymorphisms (SNPs) were identified the
      bovine ZBED6 by sequencing pooled DNA samples (Pool-Seq) and forced polymerase
      chain reaction-restriction fragment length polymorphism (forced PCR-RFLP)
      methods. In this study, we reported one mutation in the promoter and two missense
      mutations in the coding regions within the bovine ZBED6 gene, and the haplotype
      variability and extent of linkage disequilibrium (LD) in 817 individuals from the
      Qinchuan (QC) and Chinese Holstein (CH). We also investigated haplotype structure
      and linkage disequilibrium coefficients for three SNPs of ZBED6 in the study
      populations. The result of haplotype analysis of three SNPs showed that eight
      different haplotypes were identified in two breeds. The wild-type haplotype (Hap
      1: GCA) and mutant-type haplotype (Hap 8: AGG) shared by two populations
      accounted for 29.8%, 57.5%, and 8.6%, 0% of all haplotypes observed in QC and CH,
      respectively. The statistical analyses indicated that three SNPs, 23 combined
      genotypes, and 8 haplotypes were significantly associated with different growth
      traits in the QC cattle population (P < 0.05 or P < 0.01). The mutant-type
      variants and mutant haplotype were superior for growth traits; the heterozygote
      diplotype was associated with higher growth traits compared to the wild-type
      homozygote. The results of this study suggest that the ZBED6 gene possibly is a
      strong candidate gene that affects growth traits in QC beef cattle breeding
      program.

PMID- 24299184
TI  - Characterization of 5' upstream region and investigation of TTTTA deletion in 5'
      UTR of myostatin (MSTN) gene in Indian goat breeds.
AB  - Myostatin (MSTN) is a negative regulator of muscle growth and development. In the
      present study characterization of MSTN 5' upstream region and investigation of
      5'UTR TTTTA deletion was carried out in seven different Indian goat breeds. An
      1181 bp fragment of 5' upstream region of MSTN gene was PCR amplified, cloned,
      and sequenced. Nucleotide sequences of MSTN 5' upstream region exhibited a high
      degree (>99%) identity among Indian as well as non-Indian goat breeds. These
      sequences showed >96.8% and 94.8% sequence identity with those of sheep and
      cattle. In silico analysis of MSTN 5' upstream region using MatInspector program
      revealed the presence of three TATA boxes, six E-box motifs, one CAAT box, and
      other important putative regulatory elements. We identified 16 nucleotide
      substitutions in the 5' upstream region of Indian goat breeds. Screening for a
      polymorphic TTTTA deletion (Delta -10 to -6) in 5' UTR using DraI/PCR-RFLP assay
      revealed the presence of only two genotypes, namely, AA (deletion homozygotes;
      0.95) and AB (heterozygotes; 0.05) among the Indian breeds. The mutant allele A
      is almost fixed (~0.98) among Indian goat breeds and consequently, we could not
      perform the association study of this deletion with growth traits.

PMID- 24299185
TI  - Comparative sequence analysis in the exon 5 of growth hormone gene in the various
      livestock species of India.
AB  - The aim of the study was to identify genetic polymorphism in growth hormone (GH)
      gene locus of six different livestock species using PCR-Direct DNA sequencing
      method. In exon 5 of GH gene, 10 SNPs variants were identified in all livestock
      species studied, namely Bubalus bubalis, Bos indicus, Bos frontalis, Bos
      grunniens, Ovis aries, and Capra hircus. Four SNPs were observed in Bubalus
      bubalis, two SNPs in Bos indicus, one SNP in Ovis aries, and three SNPs in Capra
      hircus. No changes were observed in Bos grunniens and Bos frontalis when compared
      with the template sequence and the SNPs observed in the present investigation may
      be useful in the marker assisted selection.

PMID- 24299186
TI  - Elevated LH levels draw a stronger distinction than AMH in premature ovarian
      insufficiency.
AB  - OBJECTIVES: A significant number of individuals have high serum follicle
      stimulating hormone (FSH) levels but do not meet the criteria for diagnosis of
      premature ovarian insufficiency (POI) due to ongoing menstruation. We compared a
      group of women with elevated FSH levels and POI with a control group in terms of
      biochemical markers. METHODS: In this cross-sectional retrospective study, 38 POI
      cases and 48 cases of elevated FSH were compared to 89 individuals in a control
      arm in terms of biochemical markers. The receiver operating characteristics curve
      was calculated to assess the utility of anti-Mullerian hormone (AMH) levels to
      discriminate women with elevated FSH levels accompanied by POI from those women
      with elevated FSH levels but not defineable as having POI. RESULTS: A multiple
      regression analysis revealed that only the AMH level was significantly different
      for the discrimination between the control and elevated FSH groups. AMH and
      estradiol levels were found to be statistically significant for the
      discrimination between control and POI cases. However, only luteinizing hormone
      (LH) was found to be significant for distinguishing between women with elevated
      FSH and POI, interestingly excluding the serum AMH level in this context.
      CONCLUSIONS: AMH was the most important and superior marker to differentiate both
      POI cases and patients with an elevated FSH level from the controls; however, it
      did not show the same resolution for differentiating POI cases from those with
      elevated FSH. Moreover, we conclude that the serum LH level is the most useful
      marker for differentiating POI cases from women with elevated FSH levels.

PMID- 24299187
TI  - (De)stigmatizing the silent epidemic: representations of hearing loss in
      entertainment television.
AB  - The number of adolescents, young adults, and senior citizens experiencing hearing
      loss has significantly increased over the last 30 years. Despite this prevalence,
      hearing loss receives little attention in popular and political discourse, except
      in its connection to aging. Thus, hearing loss and the use of hearing aids have
      been stigmatized, discouraging adults from seeking hearing evaluation and
      screening, and justifying the lack of insurance coverage for hearing devices.
      This research explored how and why hearing loss continues to be stigmatized
      through a study of media messages about hearing loss. A textual analysis was
      conducted on 276 television episodes that involved d/Deaf characters and/or
      storylines about hearing loss and deafness from 1987 through 2013 (see Table 1).
      Only 11 fictional programs addressed the experience of hearing loss through 47
      episodes, including Criminal Minds, Switched at Birth, House, M.D., and New Girl.
      Contrary to the assumption that hearing loss exclusively impacts older people,
      characters were typically young, attractive, working professionals who held
      prominent roles in the programs. For most characters, hearing loss developed
      suddenly and was restored by the end of the episode, with only four characters
      using hearing aids. Hearing loss was depicted as comical, embarrassing, lonely,
      and threatening to one's work. The scarcity of hearing loss portrayals, combined
      with the negative representations of hearing loss, could help explain why hearing
      loss continues to be stigmatized and overlooked, even though almost half of all
      Americans will eventually experience difficulty hearing. 

PMID- 24299188
TI  - Genetic dissection of blood lipid traits by integrating genome-wide association
      study and gene expression profiling in a porcine model.
AB  - BACKGROUND: Serum concentrations of total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and
      triglycerides (TG) are highly heritable traits that are used clinically to
      evaluate risk for cardiovascular disease in humans. In this study, we applied a
      genome-wide association study (GWAS) in 1,075 pigs from two populations and gene
      expression studies on 497 liver samples to dissect the genetic basis of serum
      lipids in a pig model. RESULTS: We totally identified 8, 5, 2 and 3 genomic loci
      harboring 109 SNPs that were significantly associated with LDL-C, TC, TG and the
      ratio of HDL-C/LDL-C in two experimental populations, respectively. In the F2
      population, the most prominent SNP was identified at the SSC3: 124,769,847 bp
      where APOB is the well-known candidate gene. However, in the Sutai population,
      the most number of significant SNPs was identified at SSC2: 64.97-82.22 Mb where
      LDLR was identified as the candidate gene. Furthermore, we firstly reported 4
      novel genomic loci in pigs harboring the LDL-C-associated SNPs. We also observed
      obvious population heterogeneity in the two tested populations. Through whole
      genome gene expression analysis, we detected 718 trait-correlated expressions.
      Many of these transcripts correspond to candidate genes for blood lipids in
      humans. The GWAS mapped 120 cis-eQTLs and 523 trans-eQTLs for these transcripts.
      One gene encoding the transcript gnl|UG|Ssc#S35330332 stands out to be an
      important candidate gene for LDL-C by an integrative analysis of GWAS, eQTL and
      trait-associated expression. CONCLUSIONS: We identified the genomic regions or
      candidate genes associated with blood lipids by an integrative analysis of GWAS,
      QTT and eQTL mapping in pigs. The findings would benefit the further
      identification of the causative genes for blood lipid traits in both pigs and
      humans.

PMID- 24299189
TI  - Prevalence of methicillin-resistant Staphylococcus spp. in the conjunctival sac
      of healthy dogs.
AB  - OBJECTIVES: To determine the prevalence of selected coagulase-positive
      methicillin-resistant Staphylococcus aureus (MRS) in the conjunctival sac in a
      group of healthy dogs and to compare the prevalence of ocular MRS colonization
      with colonization of typically assessed body sites including the nasal cavity and
      rectum. ANIMALS STUDIED: 123 healthy dogs were used in the prevalence study: 40
      dogs from a shelter and 83 privately owned dogs. PROCEDURES: The sampling
      procedure included culturing three separate sites per subject in the following
      order: the lower conjunctival fornices, the nares, and rectum. RESULTS: A low
      prevalence of 1.6% (2/123) of MRS was detected in healthy dogs. Methicillin
      resistant Staphylococcus pseudintermedius was isolated from two dogs, one from a
      conjunctival swab and the other from a rectal swab. CONCLUSION: The survey data
      indicate the ocular surface is a potential site of MRS colonization, although the
      prevalence was low in healthy dogs.

PMID- 24299190
TI  - The integrin-linked kinase gene up-regulated by hypoxia plays its pro-survival
      role in colorectal cancer cells.
AB  - CONTEXT: Colorectal cancer (CRC) is a leading cause of cancer death in recent
      years. It is believed that there are hypoxic regions in both early and advanced
      stage of tumor and hypoxia is able to reinforce the aggressiveness of tumor cells
      and accelerate the progression of cancer. OBJECTIVE: Until now the mechanisms by
      which hypoxia promotes the progression of CRC are far from well understood.
      Integrin-linked kinase (ILK) is a crucial mediator and over-expressed in CRC
      patients. But whether ILK is involved in the process that hypoxia promotes CRC
      cells growth and silencing the ILK gene results in CRC cells apoptosis is not
      clear. MATERIALS AND METHODS: Lentivirus transfection, invasion assay, TUNEL
      assay, Bromodeoxyuridine incorporation and mitochondrial function assay were
      applied to demonstrate our hypothesis. RESULTS: In this study, we found that
      hypoxia induced the expression of ILK in a time-dependent manner, and after
      knocking down ILK expression with ILK shRNA, the cells proliferation promoted by
      hypoxia was inhibited in HT29 cell line. Moreover, blocking the ILK pathway led
      to caspase-3 and caspase-9 activations, the decrease of mitochondrial membrane
      potential, and cells apoptosis. And the inhibitory effects of hypoxia on cells
      apoptosis were mediated by the ILK pathway. In addition, hypoxia promoted HT29
      cells metastasis and invasion through the ILK pathway. CONCLUSIONS: Therefore, we
      conclude that the CRC cells survival and invasion enhanced by hypoxia are
      mediated by ILK, and ILK may be an important potential therapeutic target for
      CRC.

PMID- 24299191
TI  - Recent advances in plant membrane-bound transcription factor research: emphasis
      on intracellular movement.
AB  - Transcription factors constitute numerous signal transduction networks and play a
      central role in gene expression regulation. Recent studies have shown that a
      limited portion of transcription factors are anchored in the cellular membrane,
      storing as dormant forms. Upon exposure to environmental and developmental cues,
      these transcription factors are released from the membrane and translocated to
      the nucleus, where they regulate associated target genes. As this process skips
      both transcriptional and translational regulations, it guarantees prompt response
      to external and internal signals. Membrane-bound transcription factors (MTFs)
      undergo several unique steps that are not involved in the action of canonical
      nuclear transcription factors: proteolytic processing and intracellular movement.
      Recently, alternative splicing has also emerged as a mechanism to liberate MTFs
      from the cellular membranes, establishing an additional activation scheme
      independent of proteolytic processing. Multiple layers of MTF regulation add
      complexity to transcriptional regulatory scheme and ensure elaborate action of
      MTFs. In this review, we provide an overview of recent findings on MTFs in plants
      and highlight the molecular mechanisms underlying MTF liberation from cellular
      membranes with an emphasis on intracellular movement. 

PMID- 24299192
TI  - Assessing the cost-effectiveness of type 1 diabetes interventions: the Sheffield
      type 1 diabetes policy model.
AB  - AIMS: To build a flexible and comprehensive long-term type 1 diabetes mellitus
      model incorporating the most up-to-date methodologies to allow a number of cost
      effectiveness evaluations. METHODS: This paper describes the conceptual
      modelling, model implementation and model validation of the Sheffield type 1
      diabetes policy model (version 1.0), developed through funding by the U.K.
      National Institute for Health Research as part of the Dose Adjustment for Normal
      Eating research programme. The model is an individual patient-level simulation
      model of type 1 diabetes and it includes long-term microvascular (retinopathy,
      neuropathy and nephropathy) and macrovascular (myocardial infarction, stroke,
      revascularization and angina) diabetes-related complications and acute adverse
      events (severe hypoglycaemia and diabetic ketoacidosis). The occurrence of these
      diabetes-related complications in the model is linked to simulated individual
      patient-level risk factors, including HbA1c , age, duration of diabetes, lipids
      and blood pressure. Transition probabilities were modelled based on a combination
      of existing risk functions, published trials, epidemiological studies and
      individual-level data from the Dose Adjustment for Normal Eating research
      programme. RESULTS: The model takes a lifetime perspective, estimating the impact
      of interventions on costs, clinical outcomes, survival and quality-adjusted life
      years. Validation of the model suggested that, for almost all diabetes-related
      complications predicted, event rates were within 10% of the normalized rates
      reported in the studies used to build the model. CONCLUSIONS: The model is highly
      flexible and has broad potential application to evaluate the Dose Adjustment for
      Normal Eating research programme, other structured diabetes education programmes
      and other interventions for type 1 diabetes.

PMID- 24299193
TI  - Differential effects of temporal regularity on auditory-evoked response
      amplitude: a decrease in silence and increase in noise.
AB  - BACKGROUND: In daily life, we are continuously exposed to temporally regular and
      irregular sounds. Previous studies have demonstrated that the temporal regularity
      of sound sequences influences neural activity. However, it remains unresolved how
      temporal regularity affects neural activity in noisy environments, when attention
      of the listener is not focused on the sound input. METHODS: In the present study,
      using magnetoencephalography we investigated the effects of temporal regularity
      in sound signal sequencing (regular vs. irregular) in silent versus noisy
      environments during distracted listening. RESULTS: The results demonstrated that
      temporal regularity differentially affected the auditory-evoked N1m response
      depending on the background acoustic environment: the N1m amplitudes elicited by
      the temporally regular sounds were smaller in silence and larger in noise than
      those elicited by the temporally irregular sounds. CONCLUSIONS: Our results
      indicate that the human auditory system is able to involuntarily utilize temporal
      regularity in sound signals to modulate the neural activity in the auditory
      cortex in accordance with the surrounding acoustic environment.

PMID- 24299194
TI  - Complexity and robustness of the flavonoid transcriptional regulatory network
      revealed by comprehensive analyses of MYB-bHLH-WDR complexes and their targets in
      Arabidopsis seed.
AB  - In Arabidopsis thaliana, proanthocyanidins (PAs) accumulate in the innermost cell
      layer of the seed coat (i.e. endothelium, chalaza and micropyle). The expression
      of the biosynthetic genes involved relies on the transcriptional activity of R2R3
      MYB and basic helix-loop-helix (bHLH) proteins which form ternary complexes
      ('MBW') with TRANSPARENT TESTA GLABRA1 (TTG1) (WD repeat protein). The
      identification of the direct targets and the determination of the nature and
      spatio-temporal activity of these MBW complexes are essential steps towards a
      comprehensive understanding of the transcriptional mechanisms that control
      flavonoid biosynthesis. In this study, various molecular, genetic and biochemical
      approaches were used. Here, we have demonstrated that, of the 12 studied genes of
      the pathway, only dihydroflavonol-4-reductase (DFR), leucoanthocyanidin
      dioxygenase (LDOX), BANYULS (BAN), TRANSPARENT TESTA 19 (TT19), TT12 and H(+) 
      ATPase isoform 10 (AHA10) are direct targets of the MBW complexes. Interestingly,
      although the TT2-TT8-TTG1 complex plays the major role in developing seeds, three
      additional MBW complexes (i.e. MYB5-TT8-TTG1, TT2-EGL3-TTG1 and TT2-GL3-TTG1)
      were also shown to be involved, in a tissue-specific manner. Finally, a minimal
      promoter was identified for each of the target genes of the MBW complexes.
      Altogether, by answering fundamental questions and by demonstrating or
      invalidating previously made hypotheses, this study provides a new and
      comprehensive view of the transcriptional regulatory mechanisms controlling PA
      and anthocyanin biosynthesis in Arabidopsis. 

PMID- 24299195
TI  - Role performance of psychiatric nurses in advanced practice: a systematic review
      of the literature.
AB  - This paper discusses findings from a systematic review of literature pertaining
      to the role performance of psychiatric nurses in advanced practice. A search of
      11 electronic databases was conducted to identify research involving
      interventions by psychiatric (or mental health) nurses in advanced practice. A
      total of 14 studies were identified. In this review, the role performance of
      psychiatric nurses in advanced practice was categorized into three themes: (1)
      the provision of psychosocial interventions; (2) the provision of nurse-directed
      services in health-care contexts; and (3) the provision of psychiatric nursing
      consultation services. Our results document that psychiatric nurses in advanced
      practice perform multifaceted roles and provide mental health-care services in
      various contexts. This systematic review reveals that the nurses obtain
      significant results in managing clients with depression and psychological stress,
      and demonstrates their value when developing partnerships with non-mental health
      service providers. One study, however, showed that the nurses had insignificant
      results in performing transitional care for pre-discharged mental health service
      users.

PMID- 24299197
TI  - Strong photon energy dependence of the photocatalytic dissociation rate of
      methanol on TiO2(110).
AB  - Photocatalytic dissociation of methanol (CH3OH) on a TiO2(110) surface has been
      studied by temperature programmed desorption (TPD) at 355 and 266 nm. Primary
      dissociation products, CH2O and H atoms, have been detected. The dependence of
      the reactant and product TPD signals on irradiation time has been measured,
      allowing the photocatalytic reaction rate of CH3OH at both wavelengths to be
      directly determined. The initial dissociation rate of CH3OH at 266 nm is nearly 2
      orders of magnitude faster than that at 355 nm, suggesting that CH3OH
      photocatalysis is strongly dependent on photon energy. This experimental result
      raises doubt about the widely accepted photocatalysis model on TiO2, which
      assumes that the excess potential energy of charge carriers is lost to the
      lattice via strong coupling with phonon modes by very fast thermalization and the
      reaction of the adsorbate is thus only dependent on the number of electron-hole
      pairs created by photoexcitation. 

PMID- 24299196
TI  - Disparities in cataract surgery between Aboriginal and non-Aboriginal people in
      New South Wales, Australia.
AB  - BACKGROUND: To investigate variation in rates of cataract surgery in New South
      Wales, Australia by area of residence for Aboriginal and non-Aboriginal adults.
      DESIGN: Observational data linkage study of hospital admissions. PARTICIPANTS:
      Two hundred eighty-nine thousand six hundred forty-six New South Wales residents
      aged 30 years and over admitted to New South Wales hospitals for 444,551 cataract
      surgery procedures between 2001 and 2008. METHODS: Analysis of linked routinely
      collected hospital data using direct standardization and multilevel negative
      binomial regression models accounting for clustering of individuals within
      Statistical Local Areas. MAIN OUTCOME MEASURES: Age-standardized cataract surgery
      rates and adjusted rate ratios. RESULTS: Aboriginal people had lower rates of
      cataract procedures than non-Aboriginal people of the same age and sex, living in
      the same Statistical Local Area (adjusted rate ratio 0.71, 95% confidence
      interval 0.68-0.75). There was significant variation in cataract surgery rates
      across Statistical Local Areas for both Aboriginal and non-Aboriginal people,
      with the disparity greater in major cities and less disadvantaged areas. Rates of
      surgery were lower for Aboriginal than non-Aboriginal people in most Statistical
      Local Areas, but in a few, the rates were similar or higher for Aboriginal
      people. CONCLUSIONS: Aboriginal people in New South Wales received less cataract
      surgery than non-Aboriginal people, despite evidence of higher cataract rates.
      This disparity was greatest in urban and wealthier areas. Higher rates of surgery
      for Aboriginal people observed in some specific locations are likely to reflect
      the availability of public ophthalmology services, targeted services for
      Aboriginal people and higher demand for surgery in these populations.

PMID- 24299198
TI  - Cesarean sections and fetal death rates.

PMID- 24299199
TI  - Activation of primary sensory neurons by the topical application of capsaicin on
      the epidermis of a re-innervated organotypic human skin model.
AB  - Using an ex vivo skin-nerve preparation, skin and nerve cells were reconstituted
      into a single unit and maintained in a nutrient medium bath until required
      experimentally. Our objective was to use the epidermis as a relay for the
      induction of an electric current to the neurons following the topical application
      of capsaicin on the skin epidermis of the skin explant, an agonist of the TRPV1
      channel implicated in pruritus and pain. After 10-20 days of coculture to form
      the re-innervated skin model, we applied a solution of capsaicin directly on the
      epidermis of the skin explant (4 MUm). The resulting current was recorded using a
      path-clamp technique on the neuronal fibres. Following the topical application of
      capsaicin, spontaneous activity was triggered, as characterised by repetitive
      spikes with periods of 125, 225 or 275 ms. This study demonstrates that the skin
      explant and nerve cells preparation may receive stimuli and be used to screen
      molecules or to study signal transmission.

PMID- 24299200
TI  - Effect of rotational shepherding on demographic and genetic connectivity of
      calcareous grassland plants.
AB  - Response to habitat fragmentation may not be generalized among species, in
      particular for plant communities with a variety of dispersal traits. Calcareous
      grasslands are one of the most species-rich habitats in Central Europe, but
      abandonment of traditional management has caused a dramatic decline of calcareous
      grassland species. In the Southern Franconian Alb in Germany, reintroduction of
      rotational shepherding in previously abandoned grasslands has restored species
      diversity, and it has been suggested that sheep support seed dispersal among
      grasslands. We tested the effect of rotational shepherding on demographic and
      genetic connectivity of calcareous grassland specialist plants and whether the
      response of plant populations to shepherding was limited to species dispersed by
      animals (zoochory). Specifically, we tested competing dispersal models and source
      and focal patch properties to explain landscape connectivity with patch-occupancy
      data of 31 species. We fitted the same connectivity models to patch occupancy and
      nuclear microsatellite data for the herb Dianthus carthusianorum (Carthusian
      pink). For 27 species, patch connectivity was explained by dispersal by
      rotational shepherding regardless of adaptations to zoochory, whereas population
      size (16% species) and patch area (0% species) of source patches were not
      important predictors of patch occupancy in most species. [Correction made after
      online publication, February 25, 2014: Population size and patch area percentages
      were mistakenly inverted, and have now been fixed.] Microsite diversity of focal
      patches significantly increased the model variance explained by patch occupancy
      in 90% of the species. For D. carthusianorum, patch connectivity through
      rotational shepherding explained both patch occupancy and population genetic
      diversity. Our results suggest shepherding provides dispersal for multiple plant
      species regardless of their dispersal adaptations and thus offers a useful
      approach to restore plant diversity in fragmented calcareous grasslands.

PMID- 24299201
TI  - Fast DNA sieving through submicrometer cylindrical glass capillary matrix.
AB  - Here, we report on DNA electrophoresis through a novel artificial sieving matrix
      based on the highly regular submicrometer cylindrical glass capillary segments
      alternatingly arranged with wells. Such round capillaries pose a higher-order
      confinement resulting in a lower partition coefficient and greater entropic
      energy barrier while limiting the driving field strength to a small fraction of
      the applied electric field. In return, the separation can be performed at high
      average field strengths (up to 1.6 kV/cm) without encountering the field
      dependent loss of resolving power. This leads to fast DNA sieving as demonstrated
      here on the capillaries of 750 nm in diameter. The 600 bp to 21 kbp long chains
      are shown to resolve within 4 min after having undergone a fairly limited number
      of entropic barriers (128 in total). The capillary matrix also exhibits a
      critical field threshold below which DNA bands fail to launch, and this occurs at
      a considerably greater magnitude than in other matrixes. The submicrometer
      capillaries are batch-fabricated on silicon through a fabrication process that
      does not require high-resolution advanced lithography or well-controlled wafer
      bonding techniques to define their critical dimension. 

PMID- 24299202
TI  - Metal-metal interaction in Fischer carbene complexes: a study of ferrocenyl and
      biferrocenyl tungsten alkylidene complexes.
AB  - A series of ferrocenyl (Fc = ferrocenyl; fc = ferrocen-1,1'-diyl) and
      biferrocenyl (Bfc = 1',1"-biferrocenyl; bfc = 1',1"-biferrocen-1,1'''-diyl) mono-
      and biscarbene tungsten(0) complexes of the type [(CO)5W?C(OMe)R] (1, R = Fc; 3,
      R = Bfc) and [(CO)5W?C(OMe)-R'-(OMe)C?W(CO)5] (2, R' = fc; 4, R' = bfc) were
      synthesized according to the classical synthetic methodology by reacting W(CO)6
      with LiR (R = Fc, fc, bfc), followed by a subsequent alkylation using methyl
      trifluoromethanesulfonate. Electrochemical investigations were carried out on
      these complexes to get a closer insight into the electronic properties of 1-4.
      The ferrocenyl and biferrocenyl moieties in 1-4 show reversible one-electron
      redox events. It was further found that the Fischer carbene unit is reducible in
      an electrochemical one-electron transfer process. For the tungsten carbonyl
      moieties, irreversible oxidation processes were found. In addition, charge
      transfer studies were performed on 1-4 using in situ UV-vis-NIR and infrared
      spectroelectrochemical techniques. During the UV-vis-NIR investigations, typical
      low energy transitions for the mixed-valent biferrocenyl unit were found. A
      further observed high energy NIR absorption is attributed to a metal-metal charge
      transfer transition between the tungsten carbonyl fragment and the
      ferrocenyl/biferrocenyl group in the corresponding oxidized states, which can be
      described as class II systems according to Robin and Day. This assignment was
      verified by infrared spectroelectrochemical studies. The electrochemical
      investigations are supported by density functional theory calculations. The
      structural properties of 1-4 in the solid state were investigated by single
      crystal X-ray diffraction studies showing no substituent effects on bond lengths
      and angles. The biferrocenyl derivatives exhibit syn-conformation of the
      ferrocenyl and carbene building blocks. 

PMID- 24299203
TI  - Moderately strong phenols dissociate by forming an ion-pair kinetic intermediate.
AB  - We show computational evidence that ground-state moderately strong hydroxyarenes
      (Ar-OH, pKa ~ 0) dissociate by forming an ion-pair intermediate that lives for 3
      5 ps. The concentration of this intermediate is approximately 2 times smaller
      than that of the un-ionized acid at pH ~ 0.6 and is characterized by average C-O
      bond lengths (1.30 A) that are intermediate between those of un-ionized (1.29 A)
      and fully dissociated (1.34 A) species. During the lifetime of the ion-pair
      intermediate the excess proton fluctuates between the oxygen atom of the phenolic
      moiety and those of water molecules in the first and second solvation shells on a
      subpicosecond time scale (~100-300 fs). 

PMID- 24299205
TI  - Surface-assisted unidirectional orientation of ZnO nanorods hybridized with
      nematic liquid crystals.
AB  - Inorganic semiconductor nanorods are regarded as the primary components of
      optical and electrical nanoscale devices. In this paper, we demonstrate the
      unidirectional alignment of monolayered and dispersed ZnO nanorods on a rubbed
      polyimide alignment layer, which was achieved by a conventional liquid crystal
      alignment technique. The outermost surfaces of the ZnO nanorods (average diameter
      7 nm; length 50 nm) were modified by polymerization initiator moieties, and
      nematic liquid crystalline (LC) methacrylate polymers were grown by atom transfer
      radical polymerization. By regulating the densities of the polymerization
      initiator moieties, we successfully hybridized LC-polymer-grafted ZnO nanorods
      and small nematic LC molecules. The LC-polymer-modified ZnO nanorods were
      hierarchically aligned on the substrate via cooperative molecular interactions
      among the liquid crystal mesogens, which induced molecular orientation on the
      rubbed polyimide alignment layer. 

PMID- 24299204
TI  - A potassium leak channel silences hyperactive neurons and ameliorates status
      epilepticus.
AB  - OBJECTIVE: To develop a constitutively active K(+) leak channel using TREK-1
      (TWIK-related potassium channel 1; TREK-M) that is resistant to compensatory down
      regulation by second messenger cascades, and to validate the ability of TREK-M to
      silence hyperactive neurons using cultured hippocampal neurons. To test if
      adenoassociated viral (AAV) delivery of TREK-M could reduce the duration of
      status epilepticus and reduce neuronal death induced by lithium-pilocarpine
      administration. METHODS: Molecular cloning techniques were used to engineer novel
      vectors to deliver TREK-M via plasmids, lentivirus, and AAV using a
      cytomegalovirus (CMV)-enhanced GABRA4 promoter. Electrophysiology was used to
      characterize the activity and regulation of TREK-M in human embryonic kidney (HEK
      293) cells, and the ability to reduce spontaneous activity in cultured
      hippocampal neurons. Adult male rats were injected bilaterally with self
      complementary AAV particles composed of serotype 5 capsid into the hippocampus
      and entorhinal cortex. Lithium-pilocarpine was used to induce status epilepticus.
      Seizures were monitored using continuous video-electroencephalography (EEG)
      monitoring. Neuronal death was measured using Fluoro-Jade C staining of
      paraformaldehyde-fixed brain slices. RESULTS: TREK-M inhibited neuronal firing by
      hyperpolarizing the resting membrane potential and decreasing input resistance.
      AAV delivery of TREK-M decreased the duration of status epilepticus by 50%.
      Concomitantly it reduced neuronal death in areas targeted by the AAV injection.
      SIGNIFICANCE: These findings demonstrate that TREK-M can silence hyperexcitable
      neurons in the brain of epileptic rats and treat acute seizures. This study paves
      the way for an alternative gene therapy treatment of status epilepticus, and
      provides the rationale for studies of AAV-TREK-M's effect on spontaneous seizures
      in chronic models of temporal lobe epilepsy.

PMID- 24299207
TI  - Video laryngoscopy improves intubation success and reduces esophageal intubations
      compared with direct laryngoscopy in the medical intensive care unit.
AB  - Urgent and emergent airway management outside the operating room is fraught with
      complications due to the nature of its acuity, single or multiple system
      dysfunction or failure, and physiological disturbances. These provide a challenge
      to the airway team and place the patient at grave risk for potentially life
      threatening airway and hemodynamics-related consequences. Conventional
      laryngoscopy is rapidly being challenged by video-camera-assisted laryngoscopes
      that, in many cases, offer improved visualization of the airway. Successful
      intubation remains a lofty but attainable goal for airway specialists as well as
      the novice intubator. Yet to assume that airway management difficulties can be
      erased by incorporating a new device is optimistic but naive. In regard to
      patient safety, the device is just one piece of the airway puzzle. 

PMID- 24299208
TI  - PIK3CA gene mutations and amplifications in Chinese patients with ovarian clear
      cell carcinoma.
AB  - The role of genetic alterations in PIK3CA gene has not been fully explored in
      ovarian clear cell carcinoma (OCCC). The present study was undertaken to assess
      mutations and amplifications of exons 9 and 20 of PIK3CA in 51 Chinese OCCC
      patients. Activating missense mutations of PIK3CA were found in nine (17.6%)
      cases. One novel mutation T544P was identified in exon 9 which can increase AKT
      phosphorylation in cell culture. Amplifications of PIK3CA were observed in six
      cases (11.8%). PIK3CA mutations and amplifications are mutually exclusive. Our
      study demonstrates relatively low frequency of PIK3CA mutations and
      amplifications in OCCC. 

PMID- 24299206
TI  - The Clostridium small RNome that responds to stress: the paradigm and importance
      of toxic metabolite stress in C. acetobutylicum.
AB  - BACKGROUND: Small non-coding RNAs (sRNA) are emerging as major components of the
      cell's regulatory network, several possessing their own regulons. A few sRNAs
      have been reported as being involved in general or toxic-metabolite stress,
      mostly in Gram- prokaryotes, but hardly any in Gram+ prokaryotes. Significantly,
      the role of sRNAs in the stress response remains poorly understood at the genome
      scale level. It was previously shown that toxic-metabolite stress is one of the
      most comprehensive and encompassing stress responses in the cell, engaging both
      the general stress (or heat-shock protein, HSP) response as well as specialized
      metabolic programs. RESULTS: Using RNA deep sequencing (RNA-seq) we examined the
      sRNome of C. acetobutylicum in response to the native but toxic metabolites,
      butanol and butyrate. 7.5% of the RNA-seq reads mapped to genome outside
      annotated ORFs, thus demonstrating the richness and importance of the small
      RNome. We used comparative expression analysis of 113 sRNAs we had previously
      computationally predicted, and of annotated mRNAs to set metrics for reliably
      identifying sRNAs from RNA-seq data, thus discovering 46 additional sRNAs. Under
      metabolite stress, these 159 sRNAs displayed distinct expression patterns, a
      select number of which was verified by Northern analysis. We identified stress
      related expression of sRNAs affecting transcriptional (6S, S-box &solB) and
      translational (tmRNA & SRP-RNA) processes, and 65 likely targets of the RNA
      chaperone Hfq. CONCLUSIONS: Our results support an important role for sRNAs for
      understanding the complexity of the regulatory network that underlies the stress
      response in Clostridium organisms, whether related to normophysiology,
      pathogenesis or biotechnological applications.

PMID- 24299209
TI  - Sirtuins and cancer: new insights and cell signaling.
AB  - Sirtuins are involved in the control of the cell cycle and regulation of gene
      transcription. While some sirtuins have tumor suppressor effects, others regulate
      tumors metabolism. Within this perspective, the present article is a review of
      the current role of sirtuins in the etiology and physiopathology of cancer.
      Sirtuins show strong potential to become a valuable predictive and prognostic
      marker for cancer and are eligible as therapeutic targets for a variety of
      tumors. Investigation of new molecules able to modulate sirtuins activity must be
      encouraged. 

PMID- 24299210
TI  - Nur77 inhibits androgen-induced bladder cancer growth.
AB  - Currently, bladder cancer ranks as the second most common genitourinary
      malignancy which is exacting significant morbidity and mortality worldwide.
      Although there are abundant epidemiological and basic studies which strongly
      suggest the role of androgen hormone in bladder cancer, the underlying mechanism
      is not fully understood. In the current study, we sought to identify a new
      competitive inhibitor for androgen receptor in bladder cancer cells. Our results
      showed that Nur77 hyperexpression inhibits UM-UC-3 cell growth and cell cycle
      progression while Nur77 knockdown exerts the opposite effect. In our cell culture
      model, we also demonstrated that Nur77 competitively inhibits androgen-dependent
      transcription activity and more specifically, Nur77 competes with androgen
      receptor for binding to src-1, a well-known coactivator for steroids. More
      importantly, we also showed that a small molecule agonist for Nur77, Cytosporone
      B, significantly inhibits androgen-dependent bladder cancer cell growth in two
      different cell lines. These data provide a good proof-of-principle that Nur77
      signaling machinery could be a new target for growth control of androgen
      dependent bladder cancer cells. 

PMID- 24299212
TI  - Novel secretory protein Ss-Caf1 of the plant-pathogenic fungus Sclerotinia
      sclerotiorum is required for host penetration and normal sclerotial development.
AB  - To decipher the mechanism of pathogenicity in Sclerotinia sclerotiorum, a
      pathogenicity-defective mutant, Sunf-MT6, was isolated from a T-DNA insertional
      library. Sunf-MT6 could not form compound appressorium and failed to induce
      lesions on leaves of rapeseed though it could produce more oxalic acid than the
      wild-type strain. However, it could enter into host tissues via wounds and cause
      typical necrotic lesions. Furthermore, Sunf-MT6 produced fewer but larger
      sclerotia than the wild-type strain Sunf-M. A gene, named Ss-caf1, was disrupted
      by T-DNA insertion in Sunf-MT6. Gene complementation and knockdown experiments
      confirmed that the disruption of Ss-caf1 was responsible for the phenotypic
      changes of Sunf-MT6. Ss-caf1 encodes a secretory protein with a putative Ca(2+)
      binding EF-hand motif. High expression levels of Ss-caf1 were observed at an
      early stage of compound appressorium formation and in immature sclerotia.
      Expression of Ss-caf1 without signal peptides in Nicotiana benthamiana via
      Tobacco rattle virus-based vectors elicited cell death. These results suggest
      that Ss-caf1 plays an important role in compound appressorium formation and
      sclerotial development of S. sclerotiorum. In addition, Ss-Caf1 has the potential
      to interact with certain host proteins or unknown substances in host cells,
      resulting in subsequent host cell death. 

PMID- 24299213
TI  - Flexible routes to thiophenes.
AB  - Three convergent routes to thiophenes are described, hinging on the radical
      addition of alpha-xanthyl ketones to ethyl vinyl sulfide or to vinyl pivalate.
      The latter route ultimately proved to be the most versatile and efficient (61
      94%). 

PMID- 24299214
TI  - Pre- and post-zygotic reproductive isolation between co-occurring Mussaenda
      pubescens var. alba and M. shikokiana (Rubiaceae).
AB  - Reproductive isolation is a fundamental requirement for speciation and includes
      several sequential stages. Few studies have determined the relative contributions
      of pre- and post-zygotic reproductive isolation in plants, especially between
      relative species with clear differentiation in flower form. To investigate the
      mechanisms responsible for reproductive isolation in sympatric Mussaenda
      pubescens var. alba and Mussaenda shikokiana (Rubiaceae) in Guangxi Province,
      China, we made observations of flowering phenology, patterns of insect
      visitation, and conducted pollination experiments, including artificial
      hybridization. The two species had overlapping flowering times and were
      pollinated by overlapping pollinators; however, their relative importance
      differed significantly with M. pubescens visited more commonly by bees and M.
      shikokiana more frequently by butterflies. Using vegetative and floral characters
      and molecular evidence based on nuclear ribosomal internal and external
      transcribed spacer regions we detected seven naturally occurring hybrids among a
      sample of approximately 125 individuals. Hybrids were characterized by
      morphologies that most closely resembled their maternal parents based on
      chloroplast evidence. Studies of artificially synthesized and natural hybrids
      demonstrated that hybrid seed had very low germination rates and naturally
      occurring hybrids exhibited pollen sterility. Post-zygotic reproductive isolating
      mechanisms play a primary role in limiting gene exchange between co-occurring
      species and maintaining species integrity in areas of sympatry. 

PMID- 24299215
TI  - Molecular mechanisms involved in the response to desiccation stress and
      persistence in Acinetobacter baumannii.
AB  - Desiccation tolerance contributes to the maintenance of bacterial populations in
      hospital settings and may partly explain its propensity to cause outbreaks.
      Identification and relative quantitation of proteins involved in bacterial
      desiccation tolerance was made using label-free quantitation and iTRAQ labeling.
      Under desiccating conditions, the population of the Acinetobacter baumannii
      clinical strain AbH12O-A2 decreased in the first week, and thereafter, a stable
      population of 0.5% of the original population was maintained. Using label-free
      quantitation and iTRAQ labeling, 727 and 765 proteins, respectively, were
      detected; 584 of them by both methods. Proteins overexpressed under desiccation
      included membrane and periplasmic proteins. Proteins associated with
      antimicrobial resistance, efflux pumps, and quorum quenching were overexpressed
      in the samples subjected to desiccation stress. Electron microscopy revealed
      clear morphological differences between desiccated and control bacteria. We
      conclude that A. baumannii is able to survive long periods of desiccation through
      the presence of cells in a dormant state, via mechanisms affecting control of
      cell cycling, DNA coiling, transcriptional and translational regulation, protein
      stabilization, antimicrobial resistance, and toxin synthesis, and that a few
      surviving cells embedded in a biofilm matrix are able to resume growth and
      restore the original population in appropriate environmental conditions following
      a "bust-and-boom" strategy. 

PMID- 24299216
TI  - To Be Involved or Not to Be Involved? Using Entertainment-Education in an HIV
      Prevention Program for Youngsters.
AB  - The purpose of this study is to gain insight into factors that are associated
      with youngsters' involvement with dance4life, a global HIV-prevention program.
      The Youth Engagement Framework, which includes factors impacting youngsters'
      involvement on three levels (individual, social, and system), was used as a
      theoretical base. In total, 67 youngsters participated, with 21 of them still
      involved in dance4life's program, and 46 not. They either were individually
      interviewed or took part in subsequent online or face-to-face focus groups.
      Results show that both individual, social, and system-level factors are
      associated with youngsters' involvement. Involved youngsters have higher
      intrinsic motivation to prevent HIV, receive more social support from parents and
      friends, and are stimulated more by dance4life to remain part of their program
      than youngsters who are no longer involved. Hence, HIV-prevention programs should
      focus on all three levels simultaneously to successfully stimulate youngsters'
      involvement.

PMID- 24299217
TI  - Differential transcription profiles in Aedes aegypti detoxification genes after
      temephos selection.
AB  - The mosquito Aedes aegypti is the main vector of Dengue and Yellow Fever
      flaviviruses. The organophosphate insecticide temephos is a larvicide that is
      used globally to control Ae. aegypti populations; many of which have in turn
      evolved resistance. Target site alteration in the acetylcholine esterase of this
      species has not being identified. Instead, we tracked changes in transcription of
      metabolic detoxification genes using the Ae. aegypti 'Detox Chip' microarray
      during five generations of temephos selection. We selected for temephos
      resistance in three replicates in each of six collections, five from Mexico, and
      one from Peru. The response to selection was tracked in terms of lethal
      concentrations. Uniform upregulation was seen in the epsilon class glutathione-S
      transferase (eGST) genes in strains from Mexico prior to laboratory selection,
      while eGSTs in the Iquitos Peru strain became upregulated after five generations
      of temephos selection. While expression of many carboxyl/cholinesterase esterase
      (CCE) genes increased with selection, no single esterase was consistently
      upregulated and this same pattern was noted in the cytochrome P450 monooxygenase
      (CYP) genes and in other genes involved in reduction or oxidation of xenobiotics.
      Bioassays using glutathione-S-transferase (GST), CCE and CYP inhibitors suggest
      that various CCEs instead of GSTs are the main metabolic mechanism conferring
      resistance to temephos. We show that temephos-selected strains show no cross
      resistance to permethrin and that genes associated with temephos selection are
      largely independent of those selected with permethrin in a previous study. 

PMID- 24299218
TI  - Comparison between three types of stented pericardial aortic valves (Trivalve
      trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Aortic valve stenosis is one of the most common heart diseases in
      older patients. Nowadays, surgical aortic valve replacement is the 'gold
      standard' treatment for this pathology and the most implanted prostheses are
      biological ones. The three most implanted bovine bioprostheses are the Trifecta
      valve (St. Jude Medical, Minneapolis, MN, USA), the Mitroflow valve (Sorin Group,
      Saluggia, Italy), and the Carpentier-Edwards Magna Ease valve (Edwards
      Lifesciences, Irvine, CA, USA). We propose a randomized trial to objectively
      assess the hemodynamic performances of these bioprostheses. METHODS AND DESIGN:
      First, we will measure the aortic annulus diameter using CT-scan,
      echocardiography and by direct sizing in the operating room after native aortic
      valve resection. The accuracy of information, in terms of size and spatial
      dimensions of each bioprosthesis provided by manufacturers, will be checked.
      Their hemodynamic performances will be assessed postoperatively at the seventh
      day and the sixth month after surgery. DISCUSSION: This prospective controlled
      randomized trial aims to verify and compare the hemodynamic performances and the
      sizing of these three bioprostheses. The data obtained may help surgeons to
      choose the best suitable bioprosthesis according to each patient's morphological
      characteristics. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01522352.

PMID- 24299219
TI  - HIV/IL-2 and EBV-associated lymphoproliferative diseases: cause and effect or
      coincidence?

PMID- 24299220
TI  - CYP2B6-G516T genotype influences plasma efavirenz concentration in a Hong Kong
      population, allowing potential individualization of therapy.

PMID- 24299221
TI  - The protein phosphatase subunit PP2A-B'gamma is required to suppress day length
      dependent pathogenesis responses triggered by intracellular oxidative stress.
AB  - Oxidative stress responses are influenced by growth day length, but little is
      known about how this occurs. A combined reverse genetics, metabolomics and
      proteomics approach was used to address this question in Arabidopsis thaliana. A
      catalase-deficient mutant (cat2), in which intracellular oxidative stress drives
      pathogenesis-related responses in a day length-dependent manner, was crossed with
      a knockdown mutant for a specific type 2A protein phosphatase subunit (pp2a
      b'gamma). In long days (LD), the pp2a-b'gamma mutation reinforced cat2-triggered
      pathogenesis responses. In short days (SD), conditions in which pathogenesis
      related responses were not activated in cat2, the additional presence of the pp2a
      b'gamma mutation allowed lesion formation, PATHOGENESIS-RELATED GENE1 (PR1)
      induction, salicylic acid (SA) and phytoalexin accumulation and the establishment
      of metabolite profiles that were otherwise observed in cat2 only in LD. Lesion
      formation in cat2 pp2a-b'gamma in SD was genetically dependent on SA synthesis,
      and was associated with decreased PHYTOCHROME A transcripts. Phosphoproteomic
      analyses revealed that several potential protein targets accumulated in the
      double mutant, including recognized players in pathogenesis and key enzymes of
      primary metabolism. We conclude that the cat2 and pp2a-b'gamma mutations interact
      synergistically, and that PP2A-B'gamma is an important player in controlling day
      length-dependent responses to intracellular oxidative stress, possibly through
      phytochrome-linked pathways. 

PMID- 24299223
TI  - Safety behaviour enhances the acceptability of exposure.
AB  - Compulsive washing and contamination fears are among the most common symptoms of
      obsessive-compulsive disorder (OCD). Research suggests that exposure and response
      prevention (ERP) is effective for OCD. However, ERP is prone to dropouts and
      refusals, and a substantial proportion of clients therefore do not receive the
      care they need. A proposed solution involves the judicious use of safety
      behaviour to enhance the acceptability of exposure-based interventions. The
      current study aimed to test this proposed solution. Participants were 70
      undergraduate students who completed two exposure exercises for contamination
      fear, one with safety behaviour and one without. Participants then rated the
      acceptability of the two exercises. Exposure with safety behaviour (ESB) was
      rated as significantly more acceptable than ERP. Furthermore, subjective fear
      ratings were lower and behavioural approach to a series of contaminants was
      greater in the ESB condition. Results demonstrated the acceptability-enhancing
      potential of safety behaviour in exposure, and are discussed in terms of both
      theoretical and practical aspects of safety behaviour, exposure, and evidence
      based interventions for anxiety disorders.

PMID- 24299222
TI  - Barriers and facilitators for assessment and treatment of hepatitis C virus
      infection in the opioid substitution treatment setting: insights from the ETHOS
      study.
AB  - Provision of hepatitis C virus (HCV) assessment and treatment via opioid
      substitution treatment (OST) clinics has been posed as an effective means of
      engaging populations with high HCV prevalence. This study explores OST client and
      health professional reports concerning barriers and facilitators affecting the
      delivery and uptake of HCV care and treatment within OST settings. In-depth
      interviews were conducted with 57 clients, 16 staff from four NSW clinics
      participating in the Australian ETHOS study and three peer workers. Client
      participants included those who had not had HCV assessment; those who had HCV
      assessment only; and those who were awaiting or undertaking HCV treatment. A
      clear difference in decisions about HCV treatment emerged between participant
      groups. For those who have not been assessed, barriers to engaging with HCV care
      included the perception that they were physically well, were not experiencing HCV
      symptoms, had other life priorities and were concerned about the side effects and
      tolerability of treatment. Those who had engaged with care expressed motivations
      stemming from seeing friends becoming unwell, wanting to live longer and hearing
      positive stories of treatment. For those interested in HCV treatment, issues
      related to both provider and setting were important, such as presence of an
      engaged clinician, an accessible treatment pathway and availability of support.
      In this integrated care model, some barriers to HCV care and treatment
      (particularly those relating to health provider and the system) are minimized. In
      this setting, HCV treatment remained an unattractive option for a significant
      number of clients. Providing ways for those without HCV symptoms to be assessed
      for liver damage may be important to open up alternative conversations about HCV
      care. Further, the importance of a changing discourse of treatment is apparent
      from these data and could be enhanced by peer communication that provides
      information about successful treatment experiences. 

PMID- 24299224
TI  - Aldehyde stress-mediated novel modification of proteins: epimerization of the N
      terminal amino acid.
AB  - Various kinds of aldehyde-mediated chemical modifications of proteins have been
      identified as being exclusively covalent. We report a unique noncovalent
      modification: the aldehyde-mediated epimerization of the N-terminal amino acid.
      Epimerization of amino acids is thought to cause conformational changes that
      alter their biological activity. However, few mechanistic studies have been
      performed, because epimerization of an amino acid is a miniscule change in a
      whole protein. Furthermore, it does not produce a mass shift, making mass
      spectrometric analysis difficult. Here, we have demonstrated epimerization
      mediated by endogenous aldehydes. A model peptide, with an N-terminal l- or d
      FMRFamide, was incubated with an endogenous or synthetic aldehyde [acetaldehyde,
      methylglyoxal, pyridoxal 5'-phosphate (PLP), 4-oxo-2(E)-nonenal, 4-hydroxy-2(E)
      nonenal, d-glucose (Glc), 4- or 2-pyridinecarboxaldehyde] under physiological
      conditions. Each reaction mixture was analyzed by liquid chromatography with
      ultraviolet detection and/or electrospray ionization mass spectrometry.
      Considerable epimerization occurred after incubation with some endogenous
      aldehydes (PLP, 40.6% after 1 day; Glc with copper ions, 6.5% after 7 days).
      Moreover, the epimerization also occurred in whole proteins (human serum albumin
      and PLP, 26.3% after 1 day). Tandem mass spectrometric studies, including
      deuterium labeling and sodium borohydride reduction, suggested that the
      epimerization results from initial Schiff base formation followed by
      tautomerization to ketimine that causes the chirality to be lost. This suggests
      that the epimerization of the N-terminal amino acid can also occur in vivo as a
      post-translational modification under a high level of aldehyde stress. 

PMID- 24299225
TI  - Evaluation of a 5-day education programme in type 1 diabetes: achieving
      individual targets with a patient-centred approach.
AB  - AIMS: To evaluate if a single inpatient education training programme can achieve
      individualized therapeutic targets. METHODS: Patients with Type 1 diabetes
      participating in a flexible intensive therapy programme were consecutively
      included in a prospective monocentric study. They all participated in the same
      education programme which had a patient-centred approach. Before the
      intervention, patients were divided into three groups according to their main
      therapeutic target: Group 1, to decrease HbA1c concentration in patients with
      baseline HbA1c >= 58 mmol/mol (7.5%); Group 2, to improve quality of life and
      satisfaction with treatment in patients with baseline HbA1c < 58 mmol/mol (7.5%);
      and Group 3, to decrease the frequency of hypoglycaemic episodes in patients with
      severe or frequent hypoglycaemic episodes. Therapeutic targets were evaluated at
      12 months. Quality of life and treatment satisfaction were evaluated with
      validated questionnaires completed at baseline and 6 months. RESULTS: In Group 1
      (n = 74), the mean +/- sd HbA1c concentration decreased from 75 +/- 15 mmol/mol
      (9.0 +/-1.4%) to 68 +/-15 mmol/mol (8.4 +/- 1.4%; P < 0.001), with 53% of
      patients experiencing a decrease in HbA1c concentration of at least 6 mmol/mol
      (0.5%), without weight gain or more frequent hypoglycaemia. In Group 2 (n = 12),
      patient satisfaction with treatment improved significantly (P < 0.0001). In Group
      3 (n = 35), minor hypoglycaemia significantly decreased from a mean +/- sd of 6.6
      +/- 4.7 to 3.2 +/- 3.0 hypoglycaemic episodes/week (P < 0.001) and the incidence
      of severe hypoglycaemia dropped significantly from a mean +/- sd of 2.31 +/- 3.07
      to 0.86 +/- 2.46 episodes/patient/year (P < 0.001). CONCLUSIONS: Many patients
      with different needs, who attended the same flexible intensive therapy education
      programme, which had a patient-centred approach, were able to achieve their
      individual therapeutic targets.

PMID- 24299226
TI  - Treatment of severe ocular hypotony by monthly injections of a viscoelastic
      agent.

PMID- 24299227
TI  - Continuous high-dose antigen exposure preferentially induces IL-10, but
      intermittent antigen exposure induces IL-4.
AB  - IL-10 plays a critical role in the induction of specific T-cell tolerance. To
      date, whether IL-10 induction by antigen application is dose- or time-dependent
      remains unclear. In this study, IL-10 induction by allergen exposure was
      investigated in the several schedules. Oxazolone was repeatedly applied to mouse
      ear, and mRNA of inflammatory cytokines in lesional skins was measured. The
      results indicated that continuous high-dose antigen exposure induces IL-4 as well
      as abundant IL-10 production. Monocytes/dendritic cells and T cells are major
      source of IL-10. Allergen-specific immunotherapy is resumed before antigen
      scattering: preseason. We evaluated safe-loading dose of allergens in preseasonal
      therapy focusing Tr1 induction. Restarting immunotherapy with high dose
      effectively augmented IL-10 expression accompanied with further induction of IL-4
      and inflammatory cytokines. Therefore, the protocol restarting with low-dose
      antigen is preferential to obviate the risk of exacerbation or anaphylaxis. 

PMID- 24299228
TI  - Proceedings of the 16th Clinicopathological Conference on Renal Allograft
      Pathology. 21 July 2012, Tokyo, Japan. Introduction.

PMID- 24299229
TI  - Desensitization for prevention of chronic antibody-mediated rejection after
      kidney transplantation.
AB  - Chronic antibody-mediated rejection (C-AMR) is the most important and leading
      cause of graft loss after kidney transplantation. Although it is well known that
      chronic renal allograft dysfunction or failure is caused by various immunological
      or non-immunological factors, donor-specific anti-human leukocyte antigen
      antibodies (DSAs) are considered to be the most detrimental to graft survival and
      could cause C-AMR. Despite the use of intensive treatment for C-AMR, outcomes
      have not always been promising. Recently, prevention, rather than treatment, of C
      AMR has been attempted, and this approach appears to be a more effective option
      for reducing the incidence of C-AMR and, ultimately, improving long-term
      survival. To prevent C-AMR, removal of antibodies, inactivation of antibodies,
      and prevention of antibody production after kidney transplantation are essential.
      Preconditioning treatment including plasmapheresis, intravenous immunoglobulin,
      and rituximab injection seems the most effective of current desensitization
      protocols. In this minireview, we will focus on the prevention of C-AMR through
      desensitization and improving long-term graft survival. 

PMID- 24299230
TI  - Long-term clinicopathological impact of calcineurin inhibitor cessation without
      specific cytoreductive induction in kidney transplantation.
AB  - Calcineurin inhibitors (CNIs) have considerably improved renal allograft
      survival. However, their chronic use has various adverse effects, including
      hypertension, hyperlipidemia, and nephrotoxicity. We conducted a retrospective
      study of kidney transplant recipients using a CNI withdrawal protocol. Eleven of
      13 patients who had stable graft function on triple-drug therapy including a
      cyclosporine (CsA) were enrolled in this study. The dose of CsA was reduced by
      20% every two wks until complete withdrawal. The mean period between the baseline
      and last biopsies was 97 (range: 21-123) months. No patient had an acute
      rejection episode during follow-up. Progression of interstitial fibrosis and
      tubular atrophy was seen in five and six cases, respectively. Arteriolar
      hyalinosis improved in three cases, but worsened in four. No patient lost his
      graft during the study. The mean serum creatinine level was 1.30 +/- 0.26 mg/dL
      at baseline and stable for 10 yr after elimination (1.26 +/- 0.11 mg/dL). At the
      end of the study, four of the eleven patients had reduced their antihypertensive
      drugs, and one patient had stopped hyperlipidemia treatment. CNI withdrawal can
      be implemented safely in stable renal transplant recipients and might lead to
      improved patient outcomes. Additional specific evidence of CNI nephrotoxicity
      should be elucidated.

PMID- 24299231
TI  - Latent IgA deposition from donor kidneys does not affect transplant prognosis,
      irrespective of mesangial expansion.
AB  - INTRODUCTION: Latent mesangial immunoglobulin A (IgA) deposition in the donated
      kidney has been investigated in the context of kidney transplantation. However,
      few studies have examined the impact of mesangial expansion accompanied with IgA
      deposition. Therefore, we investigated the effects of latent IgA deposition and
      mesangial expansion on transplant prognosis following living-donor kidney
      transplantation. METHODS: We retrospectively analyzed 68 consecutive adult living
      donor kidney transplantations performed at Kagawa University Hospital. Biopsies
      were performed at pre-implantation and at one year after transplantation.
      RESULTS: Twenty kidneys exhibited latent IgA deposition in pre-implantation
      biopsies, including 14 with mesangial expansion. Latent IgA deposition was not
      associated with renal function or donor urinalysis after donation, irrespective
      of mesangial expansion. Latent IgA deposition was not significantly associated
      with graft survival rate, allograft function, abnormal urinalysis, or the
      recurrence of IgA nephropathy, irrespective of mesangial expansion. At one year
      after transplantation, IgA deposition had disappeared in 14/20 allografts.
      Estimated glomerular function rate >40 mL/min/1.73 m(2) was significantly
      associated with the disappearance of IgA deposition. CONCLUSIONS: The present
      study showed that latent IgA deposition from the donor kidney, irrespective of
      mesangial expansion, does not affect transplant prognosis following living-donor
      kidney transplantation.

PMID- 24299232
TI  - Outcome of tonsillectomy for recurrent IgA nephropathy after kidney
      transplantation.
AB  - Since 2007, we have performed tonsillectomies for patients with recurrent
      immunoglobulin A nephropathy (IgAN) after kidney transplantation. Seven patients
      with primary IgAN showed biopsy-proven recurrent IgAN after living-donor kidney
      transplantation. They had persistent proteinuria or hematuria for an average of
      40.3 months, and tonsillectomy was performed, on average, 75.6 months after
      kidney transplantation. In six patients with observation periods of more than one
      year, good remission of urinary findings was observed after tonsillectomy. We
      classified the seven patients into three types of renal injury based on
      histological findings: severe, moderate, and mild. Two patients classified with
      severe renal injury at the time of tonsillectomy had other problems, such as
      refractory hypertension and bilateral sinusitis. They followed a rapidly
      progressive clinical course. One case already had moderate histological renal
      injury. He demonstrated prompt amelioration of urinary findings after
      tonsillectomy but immediate deviation from remission of proteinuria and
      hematuria. In the four cases presenting mild renal injury at tonsillectomy, the
      improved urinary findings and serum creatinine value after tonsillectomy have
      persisted. In conclusion, tonsillectomy may be a favorable treatment for cases of
      mild-grade IgAN. However, other treatments such as antihypertensive agents and
      diet therapy may be necessary in other grades.

PMID- 24299233
TI  - Pressure-induced local lattice distortions in alpha-Co[N(CN)2]2.
AB  - This work brings together diamond anvil cell techniques, vibrational
      spectroscopies, and complementary lattice dynamics calculations to investigate
      pressure-induced local lattice distortions in alpha-Co[N(CN)2]2. Analysis of mode
      behavior and displacement patterns reveals a series of pressure-driven
      transitions that modify the CoN6 counter-rotations, distort the octahedra, and
      flatten the C-N(ax)-C linkages. These local lattice distortions may be
      responsible for the low temperature magnetic crossover. We also discuss prospects
      for negative thermal expansion and show that there is not a straightforward low
      pressure pathway between the pink alpha and blue beta ambient pressure phases of
      Co[N(CN)2]2.

PMID- 24299234
TI  - Synthesis of convex hexoctahedral Pt micro/nanocrystals with high-index facets
      and electrochemistry-mediated shape evolution.
AB  - Systematic manipulation of nanocrystal shapes is prerequisite for revealing their
      shape-dependent physical and chemical properties. Here we successfully prepared a
      complex shape of Pt micro/nanocrystals: convex hexoctahedron (HOH) enclosed with
      48 {15 5 3} high-index facets by electrochemical square-wave-potential (SWP)
      method. This shape is the last crystal single form that had not been achieved
      previously for face-centered-cubic (fcc) metals. We further realized the shape
      evolution of Pt nanocrystals with high-index facets from tetrahexahedron (THH) to
      the HOH, and finally to trapezohedron (TPH) by increasing either the upper (EU)
      or lower potential (EL). The shape evolution, accompanied by the decrease of low
      coordinated kink atoms, can be correlated with the competitive interactions
      between preferentially oxidative dissolution of kink atoms at high EU and the
      redeposition of Pt atoms at the EL. 

PMID- 24299235
TI  - Modeling deamidation in sheep alpha-keratin peptides and application to
      archeological wool textiles.
AB  - Deamidation of glutamine (Q) and asparagine (N) has been recognized as a marker
      of degradation and aging in ancient proteins. Using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to study
      deamidation in wool textiles, we identified eight peptides from alpha-keratin
      proteins in sheep wool that could potentially be used to assess the level of
      degradation. For each chosen peptide, the extent of deamidation was determined by
      comparing the calculated theoretical distribution with the measured distribution
      using a genetic algorithm that gives the best fit to the measured distribution.
      Variations in the levels of deamidation were observed between peptides and in
      modern wool samples buried for up to 8 years in which deamidation levels were
      relatively low under short-term burial. In contrast, deamidation was higher in
      archeological textile fragments from medieval sites ranging from the 9th to 13th
      century in York (United Kingdom) and Newcastle (United Kingdom) and from the 13th
      to 16th century in Reykholt (Iceland). Major differences were observed between
      the British and the Icelandic samples, showing a negative correlation between age
      of samples and levels of deamidation, but highlighting the effect of local
      environment. In addition, nanoscale liquid chromatography-electrospray ionization
      tandem mass spectrometry (nanoLC-ESI-MS/MS) data indicated that deamidation in
      wool's alpha-keratin was influenced by primary and higher-order structures.
      Predominance of deamidation on glutamine rather than asparagine in the
      archeological samples was attributed to a higher abundance of Q in the alpha
      helical core domain of keratins, neighboring residues and steric hindrance
      preventing deamidation of N. 

PMID- 24299236
TI  - Reply: Admission cardiotocography: practice based on evidence or assumptions and
      untested theories?

PMID- 24299237
TI  - Bioreducible POSS-cored star-shaped polycation for efficient gene delivery.
AB  - The bioreducible star-shaped gene vector (POSS-(SS-PDMAEMA)8) with well-defined
      structure and relatively narrow molecular weight distribution was synthesized via
      atom transfer radical polymerization (ATRP) of (2-dimethylamino)ethyl
      methacrylate (DMAEMA) from a polyhedral oligomeric silsesquioxane (POSS)
      macroinitiator. POSS-(SS-PDMAEMA)8 was composed of a biocompatible POSS core and
      eight disulfide-linked PDMAEMA arms, wherein the PDMAEMA chain length could be
      adjusted by controlling polymerization time. POSS-(SS-PDMAEMA)8 can effectively
      bind pDNA into uniform nanocomplexes with appropriate particle size and zeta
      potential. The incorporation of disulfide bridges gave the POSS-(SS-PDMAEMA)8
      material facile bioreducibility. In comparison with POSS-(PDMAEMA)8 without
      disulfide linkage, POSS-(SS-PDMAEMA)8 exhibited much lower cytotoxicity and
      substantially higher transfection efficiency. The present work would provide
      useful information for the design of new POSS-based drug/gene carriers. 

PMID- 24299238
TI  - Molecular structural transformations induced by spatial confinement in barium
      fluoride cells.
AB  - Confinement of peptides and surfactants in narrow spaces of the order of 50 MUm
      between BaF2 plates is found to induce new structural transformations. Optical
      microscopy, transmission electron microscopy, and vibrational spectroscopic
      studies have been used to uncover the evidence for these structural
      transformations. These studies indicate that, using spatial confinement, small
      micelles can be converted to larger aggregates and peptide monomers can be
      converted to beta sheets even in monomer-promoting 1,1,1,3,3,3-hexafluoro-2
      propanol solvent. 

PMID- 24299239
TI  - Comparing the reliability of voluntary and evoked muscle actions.
AB  - PURPOSE: The purpose of this exploratory study was to quantify the test-retest
      reliability, intertrial variability and correlations between variables calculated
      during voluntary and evoked muscle actions. METHODS: During three separate trials
      of isometric leg extension muscle actions with 14 men [mean age (+/- SD) = 21.9
      (+/- 3.2) years; height = 179.2 (+/- 8.0) cm; mass = 77.7 (+/- 10.9) kg], peak
      torque (PT(V)), time to peak torque (TPT(V)), rate of torque development
      (RTD(V)), time to peak rate of torque development (TRTD(V)), electromechanical
      delay (EMD(V)) and EMG amplitude (EMG(RMS)) were quantified for voluntary muscle
      actions. Peak twitch torque (PTE ), time to peak twitch torque (TPT(E)), rate of
      torque development (RTD(E)), time to peak rate of torque development (TRTD(E)),
      electromechanical delay (EMD(E)), peak-to-peak M-wave (Mp-p) and M-wave area
      (M(area)) were calculated for evoked twitches. All electromyographic measurements
      were recorded over the vastus lateralis. RESULTS: Voluntary intraclass
      correlation coefficients (ICC) were 0.84-0.96, except for TRTD(V) (0.30) and
      EMD(V) (0.74). Evoked ICC were 0.80-0.95, except for EMD(E) (0.52). Relative
      standard errors of measurement for TPT and TRT(D) were greater for voluntary than
      evoked, whereas the value for PTE was greater than PT(V). There were low to
      moderate correlations (r = -0.41-0.51) between common voluntary and evoked
      variables. CONCLUSIONS: Evoked variables showed lower intertrial variability than
      voluntary. Overall, voluntary and evoked muscle actions provide unique,
      complimentary information regarding neuromuscular function that cannot be used
      interchangeably.

PMID- 24299241
TI  - Shame, sexual compulsivity, and eroticizing flirtatious others: an experimental
      study.
AB  - Clinical observation and correlational studies with nonclinical samples suggest
      that a linkage between negative affective states (especially shame) and
      engagement in erotic pursuits typifies sexual compulsivity. The present study
      tested whether experimental induction of shame leads to increased interest in
      erotically suggestive targets among more sexually compulsive individuals. A total
      of 74 age-traditional heterosexual university students first recalled either an
      emotionally neutral or a shame-inducing personal experience, then completed a
      nonpredictive gaze-cueing task featuring flirtatious or emotionally neutral faces
      of the same or opposite sex. They also rated the faces' attractiveness and
      completed a validated sexual compulsivity scale and two control measures
      (executive control, sociosexuality). Higher (versus lower) sexual compulsivity
      predicted weaker gaze-triggered attentional orienting in response to the
      flirtatious opposite-sex face in the shame (versus neutral) condition, and this
      was accounted for by (higher) attractiveness ratings of the flirtatious opposite
      sex face. Shame thus appears to increase sexualization (i.e., reduces salience of
      agentic features and increases appeal of physical attributes) of erotically
      suggestive targets among more sexually compulsive individuals. 

PMID- 24299242
TI  - Editorial: an overview of data-based papers on undergraduate nurse education
      recently published in Contemporary Nurse: Progress, challenges and the need for a
      strategic agenda.

PMID- 24299240
TI  - atpE gene as a new useful specific molecular target to quantify Mycobacterium in
      environmental samples.
AB  - BACKGROUND: The environment is the likely source of many pathogenic mycobacterial
      species but detection of mycobacteria by bacteriological tools is generally
      difficult and time-consuming. Consequently, several molecular targets based on
      the sequences of housekeeping genes, non-functional RNA and structural ribosomal
      RNAs have been proposed for the detection and identification of mycobacteria in
      clinical or environmental samples. While certain of these targets were proposed
      as specific for this genus, most are prone to false positive results in complex
      environmental samples that include related, but distinct, bacterial genera.
      Nowadays the increased number of sequenced genomes and the availability of
      software for genomic comparison provide tools to develop novel, mycobacteria
      specific targets, and the associated molecular probes and primers. Consequently,
      we conducted an in silico search for proteins exclusive to Mycobacterium spp.
      genomes in order to design sensitive and specific molecular targets. RESULTS:
      Among the 3989 predicted proteins from M. tuberculosis H37Rv, only 11 proteins
      showed 80% to 100% of similarity with Mycobacterium spp. genomes, and less than
      50% of similarity with genomes of closely related Corynebacterium, Nocardia and
      Rhodococcus genera. Based on DNA sequence alignments, we designed primer pairs
      and a probe that specifically detect the atpE gene of mycobacteria, as verified
      by quantitative real-time PCR on a collection of mycobacteria and non
      mycobacterial species. The real-time PCR method we developed was successfully
      used to detect mycobacteria in tap water and lake samples. CONCLUSIONS: The
      results indicate that this real-time PCR method targeting the atpE gene can serve
      for highly specific detection and precise quantification of Mycobacterium spp. in
      environmental samples.

PMID- 24299243
TI  - Scope of practice for Australian enrolled nurses: evolution and practice issues.
AB  - Significant changes to the scope of practice for enrolled nurses have occurred in
      Australia over the past decade. These changes, which are largely a consequence of
      staff shortages and economic pressure, have resulted in increased role confusion
      and overlap between enrolled and registered nurses in Australia. This paper
      presents a brief history of the enrolled nurse in Australia followed by an
      overview of the current situation and emerging trends in the education and
      employment of these nurses. Definitions and approaches to scope of practice are
      described and emerging issues within Australia raised and discussed. A review of
      the literature found the number of enrolled nurses and the roles they perform
      have changed significantly in Australia following the introduction of the
      enhanced scope of practice. Further research is required to better define and
      delineate between the different nursing roles and to explore broader frameworks
      to analyze, describe and define these roles.

PMID- 24299244
TI  - An investigation of a symptom cluster in Chinese patients with lung cancer
      receiving radiotherapy.
AB  - BACKGROUND: The investigation of the clustering of symptoms in patients with
      cancer is still at an early stage. Initial evidence suggests symptoms such as
      breathlessness, fatigue and anxiety occur concurrently. PURPOSE: The purpose of
      this study was to investigate the existence of a symptom cluster involving
      breathlessness, fatigue and anxiety in Chinese patients with advanced lung cancer
      undergoing palliative radiotherapy (RT). METHODS: The study was conducted in an
      oncology out-patient unit of a publicly funded hospital in Hong Kong. A
      convenience sample of 140 patients were asked to complete a set of questionnaires
      at four time points including the A-state scale of the State-Trait Anxiety
      Inventory, a breathlessness visual analog scale and the intensity subscale of the
      revised Piper Fatigue Scale at four points: 1 day prior to RT (baseline) (T0),
      and at week 3 (T1), week 6 (T2) and week 12 (T3) after the commencement of the
      RT. RESULTS: Between 64-73% of patients experienced all three symptoms
      concurrently across T0-T3. The prevalence of anxiety, fatigue and breathlessness
      ranged from 65-97% respectively. Intensities of breathlessness and fatigue were
      highest at T1. Significant correlations between the three symptoms were moderate
      across time (r < 0.50). CONCLUSION AND IMPLICATION: The high prevalence of the
      symptom cluster demonstrates a need to assess and manage these symptoms
      simultaneously in patients with advanced lung cancer.

PMID- 24299245
TI  - Effectiveness of clinical teaching associate model in nursing education: results
      from a developing country.
AB  - BACKGROUND AND OBJECTIVES: The credit of the practice nurses in developing
      countries, due to a gap between theory and practice in nursing education and
      healthcare delivery, has been questioned by nursing professionals. Therefore, the
      aims of this study were to investigate the effectiveness of the application of
      the clinical teaching associate (CTA) model in nursing students' clinical skills
      and to assess the participants' (faculty members, staff nurses, and nursing
      students) level of satisfaction with the CTA model and with achieving the
      educational goals in Iran, as a developing country. METHODS AND MATERIALS: In
      this experimental study, random sampling was used to assess 104 nursing students'
      clinical skills, and assess six faculty members and six staff nurses. After
      obtaining informed consent, the level of satisfaction was evaluated by a
      questionnaire and clinical skills were evaluated by standard checklists. Data
      were assessed and analyzed with SPSS version 15. RESULTS: The results showed that
      the mean scores of all clinical skills of the students were significantly higher
      after intervention (P < 0.01). Moreover, the mean scores of instructors'
      satisfaction with applying the CTA model was significantly higher (P = 0.004),
      but their satisfaction with achieving clinical education outcomes did not show a
      significant difference (P = 0.109). Similarly, students' satisfaction with
      achieving educational outcomes did not show any significant differences between
      the two groups (P = 0.058). CONCLUSION: According to this study, the CTA model is
      an effective method for developing clinical skills in nursing students in Iran as
      a developing country. Therefore, application of the method is recommended in
      clinical nursing education systems of such countries.

PMID- 24299246
TI  - Staff response time to call lights and unit-acquired pressure ulcer rates in
      adult in-patient acute care units.
AB  - The US National Pressure Ulcer Advisory Panel claimed that most pressure ulcers
      are avoidable (2007). Identifying nursing-process indicators that are objective
      and associated with pressure ulcer rates is desperately needed. As a result, the
      purpose of this exploratory study was to examine the relationship between staff
      response time to call lights and the rate for unit-acquired pressure ulcers stage
      II and greater, in adult in-patient acute care units. We used archived data of
      one Michigan hospital located in the United States from July 2005 to December
      2008 for analyses. The unit of analysis was the patient care unit-month. Pearson
      product-moment correlation analyses were used. The results showed that a faster
      staff response time to call lights was found to be associated with a lower
      percentage of unit-acquired pressure ulcers stage II and greater among surveyed
      patients. Staff response time is a significant process indicator to predict unit
      acquired pressure ulcer rates.

PMID- 24299247
TI  - 'Diabetes is nothing': the experience of older Singaporean women living and
      coping with type 2 diabetes.
AB  - PURPOSE: The purpose of this study was to describe, through qualitative methods,
      the experiences and ways of coping of older Singaporean Chinese women with type 2
      diabetes. METHODS: Using a qualitative approach, 10 Singaporean Chinese women
      between the ages of 60-69 described their experiences of living and coping with
      type 2 diabetes. Data were collected via semi-structured interviews and analysed
      using thematic analysis. RESULTS: Three themes were identified in the analysis:
      (i) Living with diabetes; (ii) Coping with diabetes; and (iii) Caring for the
      self in diabetes. CONCLUSIONS: Findings indicate that women living and coping
      with diabetes confront numerous issues. In order to help these patients initiate
      and sustain lifestyle modifications, healthcare providers are encouraged to be
      empathetic and supportive and an understanding of the coping strategies used will
      ensure that effective coping strategies are utilised. Furthermore, diabetes
      education for family members will assist them to provide essential, ongoing
      support for the patient.

PMID- 24299248
TI  - Determination of the use of complementary and alternative medicine by women in
      the climacteric period in the Turkish city of Samsun.
AB  - This quantitative descriptive study was carried out in order to determine the use
      of complementary and alternative medicine (CAM) for management of menopausal
      symptoms in women in Samsun, Turkey. Data on general demographic characteristics,
      menopause-related symptoms, and the use of CAM and herbal therapy were collected
      from 281 women undergoing the process of the climacteric period, admitted to the
      gynaecology polyclinic of a hospital in Samsun province. To evaluate the data,
      descriptive statistics, Student t-tests, and logistic regression analysis were
      used. In this study the most common CAM methods were identified as herbal therapy
      (29.9%), dieting (29.5%), exercise (29.2%), and massage (27.8%). Approximately
      one-third of the women identified as benefitting from CAM methods. More than half
      identified as not having informed a health care professional about their use of
      these methods of achieving symptom relief.

PMID- 24299249
TI  - Nurses' perceptions of parent empowerment in chronic illness.
AB  - BACKGROUND: Parent empowerment is upheld as a creative strategy to provide a
      family-centred care in chronic childhood illness. However identifying and
      measuring parent empowerment practices are ambiguous probably due to the
      subjective nature of the concept. AIM: To explore nurses' perception of parent
      empowerment in chronic illness. Design Qualitative descriptive design. METHOD:
      Three focus group interviews were conducted among a purposeful sample of child
      health nurses (N =14) and the data was analysed using qualitative content
      analysis strategy. RESULTS: The participants identified that empowered parents
      are able to take care of their child in a safe and structured way at home. An
      atmosphere of trust, open communication, shared decision making, support and
      parental readiness to accept their child's care led to parent empowerment.
      Nurse's role was identified as an advocate for the child and the family and, as a
      frontline worker who fill the gap between parent and the multidisciplinary team.
      CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Educating parents about their
      child's condition, teaching them the needed new skills, and offering and
      providing them with support services are identified as the parent empowerment
      strategies. It is recommended that further training and clear clinical guidelines
      are needed to accomplish parent empowerment.

PMID- 24299250
TI  - Choosing and remaining in nursing: Iranian male nurses' perspectives.
AB  - Iranian male nurses' career-choosing practices have not been well investigated.
      The aim of this study was to explore the reasons why Iranian male nurses choose
      nursing as a career. In addition it sought to understand the reasons why they
      remain in nursing. An exploratory descriptive design, employing a qualitative
      approach was used. Eighteen semi-structured interviews were conducted and
      analyzed using content analysis. The analysis culminated in the development of
      three themes which described the participants' motivations for choosing nursing
      as a career as well as the factors that influenced their decisions to remain in
      nursing following qualification. Practical motivations such as job security were
      important factors in choosing nursing. The most common reason for remaining in
      nursing was desire to care for others, for God's sake. Factors that influenced
      their decision to leave mainly centered on the public view to nursing as a
      feminine discipline. However, the nurses in this study believed that nursing was
      a profession appropriate for both men and women because of gendered nursing care
      and preferences of patient in Iran.

PMID- 24299251
TI  - Referrals to hospital emergency departments from residential aged care
      facilities: stuck in a time warp.
AB  - This research aimed to describe the number and type of residents admitted to
      emergency departments (EDs) over 2 years; and to explore nurses' perceptions of
      the reasons why residential aged care facility (RACF) residents are referred to
      EDs. The research objective was addressed in a retrospective exploratory study
      using data on admissions to EDs from RACFs (N = 3,094) at the participating
      organisation over a 2-year period, and interview data on seven RACF and four ED
      nurses' perceptions of the issues involved. Most residents presenting at EDs
      required urgent medical attention. Major themes identified by RACF and ED nurses
      included issues related to staff competency, availability of general
      practitioners, lack of equipment in RACFs, residents and family members
      requesting referrals, communication difficulties, and poor attitudes towards RACF
      staff. There is a need to use strategies to detect residents whose conditions are
      deteriorating and treat them promptly in RACFs.

PMID- 24299252
TI  - Social and demographic determinants for breastfeeding in a rural, suburban and
      city area of South East China.
AB  - Breastfeeding is a traditional practice in China, yet few studies have explored
      its current trend after socioeconomic reform. This study aims to characterize
      breastfeeding rates and possible associations with sociodemographic factors using
      a breastfeeding questionnaire administered to 1,385 mothers of 6-year-old
      children. Rates were lowest among city residents and negatively associated with
      parental and grandmother education levels as well as mothers' professional
      occupational status. These findings highlight the impact of urbanization on
      maternal and child health and the effect of marketing tactics for breast milk
      substitutes (BMS). Public health education promoting breastfeeding should target
      urban families, particularly those educated.

PMID- 24299253
TI  - Residents' perceptions and experiences of social interaction and participation in
      leisure activities in residential aged care.
AB  - Social interaction and participation in leisure activities are positively related
      to the health and well-being of elderly people. The main focus of this
      exploratory study was to investigate elderly peoples' perceptions and experiences
      of social interaction and leisure activities living in a residential aged care
      (RAC) facility. Six residents were interviewed. Themes emerging from discussions
      about their social interactions included: importance of family, fostering
      friendships with fellow residents, placement at dining room tables, multiple
      communication methods, and minimal social isolation and boredom. Excursions away
      from the RAC facility were favourite activities. Participants commonly were
      involved in leisure activities to be socially connected. Poor health, family, the
      RAC facility, staffing, transportation, and geography influenced their social
      interaction and participation in leisure activities. The use of new technologies
      and creative problem solving with staff are ways in which residents could enhance
      their social lives and remain engaged in leisure activities.

PMID- 24299254
TI  - The provision of health and social care services for older people by respite
      providers.
AB  - Respite services have been established to support family carers by providing a
      break from the responsibilities of caregiving. However the literature and
      anecdotal evidence suggests that respite services offer carers much more than
      just providing a period of rest. This study was initiated to identify and
      describe the health and social care services that are offered to family carers
      and care-recipients by respite services in South Australia. The findings show
      that respite providers offer a service to both the family carer and care
      recipient. Both groups are offered socialisation and engagement opportunities,
      and care-recipients have access to a diverse range of health care services. The
      description of respite that emerges from this study is that of a complex service
      offering much more than just a period of rest from caregiving duties.

PMID- 24299255
TI  - Promoting integrity in the workplace: a priority for all academic health
      professionals.
AB  - The performance-driven culture of universities challenges faculty to meet
      workplace expectations. In this paper, we draw on the literature to identify key
      aspects of, and requirements for, promoting integrity in the academic workplace.
      Integrity is a crucial personal characteristic that can exert a powerful
      influence in any setting. Any threat to integrity in the workplace can result in
      a toxic and corrupt environment that may be deleterious to faculty and students.
      Such an environment can act to prevent faculty from speaking up about ethical
      issues or workplace concerns, which can result in failure to identify areas for
      improvement, continuation of suboptimal practices, and problematic professional
      relationships. The aim of this paper, therefore, is to present an overview of the
      concept of integrity in the academic workforce and to discuss some of the issues
      and dimensions, in the hope of creating greater awareness. This is essential if
      health professional faculties are to recruit and retain staff and create optimal
      working environments conducive to facilitating high quality outcomes.

PMID- 24299256
TI  - Opinion Piece: honouring the wishes of a dying patient: from intensive care to
      home with palliative care.
AB  - Due to the severity of illness, death is not uncommon in intensive care units
      (ICU). Unfortunately, a major percentage of deaths in ICU are patients diagnosed
      with a terminal disease. Initiating discussions on the transition from curative
      care to palliative care can be stressful for doctors, patients and families. The
      challenge for doctors, is to maintain open communication and shared-decision
      making with patients and family members at this very sensitive time. This can be
      challenging due to the culture of ICU which focuses on saving lives rather than
      palliation. Facilitating discussions for terminally ill patients in ICU may
      enhance their end-of-life care and assist patients to die in an environment of
      their choice such as their home.

PMID- 24299258
TI  - Expert knowledge elicitation using computer simulation: the organization of frail
      elderly case management as an illustration.
AB  - BACKGROUND: Various elderly case management projects have been implemented in
      Belgium. This type of long-term health care intervention involves contextual
      factors and human interactions. These underlying complex mechanisms can be
      usefully informed with field experts' knowledge, which are hard to make explicit.
      However, computer simulation has been suggested as one possible method of
      overcoming the difficulty of articulating such elicited qualitative views.
      METHODS: A simulation model of case management was designed using an agent-based
      methodology, based on the initial qualitative research material. Variables and
      rules of interaction were formulated into a simple conceptual framework. This
      model has been implemented and was used as a support for a structured discussion
      with experts in case management. RESULTS: The rigorous formulation provided by
      the agent-based methodology clarified the descriptions of the interventions and
      the problems encountered regarding: the diverse network topologies of health care
      actors in the project; the adaptation time required by the intervention; the
      communication between the health care actors; the institutional context; the
      organization of the care; and the role of the case manager and his or hers
      personal ability to interpret the informal demands of the frail older person.
      CONCLUSION: The simulation model should be seen primarily as a tool for thinking
      and learning. A number of insights were gained as part of a valuable cognitive
      process. Computer simulation supporting field experts' elicitation can lead to
      better-informed decisions in the organization of complex health care
      interventions.

PMID- 24299257
TI  - Comparison of usual podiatric care and early physical therapy intervention for
      plantar heel pain: study protocol for a parallel-group randomized clinical trial.
AB  - BACKGROUND: A significant number of individuals suffer from plantar heel pain
      (PHP) and many go on to have chronic symptoms and continued disability.
      Persistence of symptoms adds to the economic burden of PHP and cost-effective
      solutions are needed. Currently, there is a wide variation in treatment, cost,
      and outcomes of care for PHP with limited information on the cost-effectiveness
      and comparisons of common treatment approaches. Two practice guidelines and
      recent evidence of effective physical therapy intervention are available to
      direct treatment but the timing and influence of physical therapy intervention in
      the multidisciplinary management of PHP is unclear. The purpose of this
      investigation is to compare the outcomes and costs associated with early physical
      therapy intervention (ePT) following initial presentation to podiatry versus
      usual podiatric care (uPOD) in individuals with PHP. METHODS: A parallel-group,
      block-randomized clinical trial will compare ePT and uPOD. Both groups will be
      seen initially by a podiatrist before allocation to a group that will receive
      physical therapy intervention consisting primarily of manual therapy, exercise,
      and modalities, or podiatric care consisting primarily of a stretching handout,
      medication, injections, and orthotics. Treatment in each group will be directed
      by practice guidelines and a procedural manual, yet the specific intervention for
      each participant will be selected by the treating provider. Between-group
      differences in the Foot and Ankle Ability Measure 6 months following the initial
      visit will be the primary outcome collected by an independent investigator. In
      addition, differences in the European Quality of Life--Five Dimensions, Numeric
      Pain Rating Scale, Global Rating of Change (GROC), health-related costs, and cost
      effectiveness at 6 weeks, 6 months, and 1 year will be compared between groups.
      The association between successful outcomes based on GROC score and participant
      expectations of recovery generally, and specific to physical therapy and podiatry
      treatment, will also be analyzed. DISCUSSION: This study will be the first
      pragmatic trial to investigate the clinical outcomes and cost-effectiveness of
      ePT and uPOD in individuals with PHP. The results will serve to inform clinical
      practice decisions and management guidelines of multiple disciplines. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01865734.

PMID- 24299259
TI  - Glia and epilepsy: experimental investigation of antiepileptic drugs in an
      astroglia/microglia co-culture model of inflammation.
AB  - PURPOSE: The contribution of glial cells, mainly astrocytes and microglia, to the
      pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role
      in the initiation and maintenance of the central nervous system (CNS) immune
      response and neuronal metabolic and trophic supply. Recent clinical and
      experimental evidence suggests a direct relationship between epileptic activity
      and CNS inflammation, which is characterized by accumulation, activation, and
      proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms
      of action of several antiepileptic drugs (AEDs) have been proposed. However,
      their direct effects on glial cells have been rarely investigated. We aimed to
      investigate the effect of commonly used AEDs on glial viability, the gap
      junctional network, the microglial activation, and cytokine expression in an in
      vitro astroglia/microglia co-culture model. METHODS: Primary astrocytic cultures
      were prepared from brains of postnatal (P0-P2) Wistar rats and co-cultured with a
      physiologic amount of 5%, as well as 30% microglia in order to mimic inflammatory
      conditions. Co-cultures were treated with valproic acid (VPA), carbamazepine
      (CBZ), phenytoin (PHE), and gabapentin (GBT). Viability and proliferation were
      measured using the tetrazolium (MTT) assay. The microglial activation state was
      determined by immunocytochemical labeling. The astroglial connexin 43 (Cx43)
      expression was measured by Western blot analysis. The transforming growth factor
      beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels
      were measured by the quantitative sandwich enzyme immunosorbent assay (ELISA).
      KEY FINDINGS: Astrocytes, co-cultured with 5% microglia (M5 co-cultures), showed
      a dose-dependent, significant reduction in glial viability after incubation with
      PHE and CBZ. Furthermore, VPA led to highly significant microglial activation at
      all doses examined. The antiinflammatory cytokine TGF-beta1 release was induced
      by high doses of GBT and PHE. Astrocytes co-cultured with 30% microglia (M30 co
      cultures) revealed a dose-dependent significant reduction in glial viability
      after incubation with PHE, accompanied by increased TGF-beta1 and TNF-alpha
      levels. However, CBZ significantly reduced the amount of activated microglial
      cells and increased the total number of inactivated microglia. Finally, CBZ
      resulted in reduced viability at all doses examined. SIGNIFICANCE: CNS
      inflammation is characterized by a disturbance of glial cell functions. Strong
      microglial activation, a typical hallmark of inflammation, was induced by VPA in
      M5 and continued in M30 co-cultures. With regard to the direct relation between
      CNS inflammation and seizures, VPA seems to be unsuitable for reducing
      inflammatory conditions. The reverse effect was achieved after CBZ. We noticed
      significant microglial inactivation, after incubation of the M30 co-cultures. In
      conclusion, we suggest that AEDs with antiinflammatory glial features are
      beneficial for seizures caused by persistent brain inflammation.

PMID- 24299260
TI  - Synthesis and characterization of divalent manganese, iron, and cobalt complexes
      in tripodal phenolate/N-heterocyclic carbene ligand environments.
AB  - Two novel tripodal ligands, (BIMPN(Mes,Ad,Me))(-) and (MIMPN(Mes,Ad,Me))(2-),
      combining two types of donor atoms, namely, NHC and phenolate donors, were
      synthesized to complete the series of N-anchored ligands, ranging from chelating
      species with tris(carbene) to tris(phenolate) chelating arms. The complete ligand
      series offers a convenient way of tuning the electronic and steric environment
      around the metal center, thus, allowing for control of the complex's reactivity.
      This series of divalent complexes of Mn, Fe, and Co was synthesized and
      characterized by (1)H NMR, IR, and UV/vis spectroscopy as well as by single
      crystal X-ray diffraction studies. Variable-temperature SQUID magnetization
      measurements in the range from 2 to 300 K confirmed high-spin ground states for
      all divalent complexes and revealed a trend of increasing zero-field splitting
      |D| from Mn(II), to Fe(II), to Co(II) complexes. Zero-field (57)Fe Mossbauer
      spectroscopy of the Fe(II) complexes 3, 4, 8, and 11 shows isomer shifts delta
      that increase gradually as carbenes are substituted for phenolates in the series
      of ligands. From the single-crystal structure determinations of the complexes,
      the different steric demand of the ligands is evident. Particularly, the
      molecular structure of 1-in which a pyridine molecule is situated next to the Mn
      Cl bond-and those of azide complexes 2, 4, and 6 demonstrate the flexibility of
      these mixed-ligand derivatives, which, in contrast to the corresponding
      symmetrical TIMEN(R) ligands, allow for side access of, e.g., organic substrates,
      to the reactive metal center. 

PMID- 24299261
TI  - Syncope among U.S. Air Force basic military trainees, August 2012-July 2013.
AB  - Syncope is a common event with many possible etiologies, ranging from benign to
      severe. Syncopal episodes of any origin, however, may result in traumatic injury
      due to postural collapse. Based on the prevalence of internal and external
      stressors during training, basic military trainees may be at increased risk for
      syncope. Between 1 August 2012 and 31 July 2013, there were 112 unique
      individuals who experienced syncopal or pre-syncopal events among basic military
      trainees at Joint Base San Antonio-Lackland, Texas, the only basic training site
      in the U.S. Air Force. The overall rate was 19.6 cases per 1,000 person-years
      (18.4 and 36.1 per 1,000 person-years in males and females, respectively). Based
      upon the findings of electronic chart review of the 112 cases, a majority of
      events occurred either during or immediately after exercise (n=38) or during a
      blood draw, immunization, or laceration repair (n=22). The most common etiologies
      were judged to be neurocardiogenic (n=54) and orthostatic hypotension (n=40), and
      two cases were attributed to cardiovascular disease. These findings support
      current preventive measures, including anemia screening during medical in
      processing, an emphasis on hydration throughout training, and a padded floor in
      the trainee vaccination bay. 

PMID- 24299262
TI  - Syncope, active and reserve components, U.S. Armed Forces, 1998-2012.
AB  - During the period of 1 January 1998 to 31 December 2012, the health care records
      of 153,172 active component service members documented at least one health care
      encounter with a diagnosis of "syncope and collapse" (overall incidence rate of
      7.2 cases per 1,000 person-years). The annual incidence rates rose by 89 percent
      during the period. During the 15-year surveillance period, there were 4,954
      instances of a documented health care encounter with a diagnosis of syncope on
      the same day that the service member had received an immunization by injection.
      Annual rates of syncope associated with immunization ranged from a low of 4.4
      events per 100,000 immunization episodes in 1998 to a maximum of 14.1 events per
      100,000 episodes in 2006. For both syncope diagnoses in general and syncope
      associated with immunization, rates were higher among women than men and were
      highest among those under age 20. Nearly ten percent of syncopal events
      associated with immunization occurred during the first two weeks of military
      service. Rates of syncope increased with the number of injections received per
      immunization episode. Diagnoses of physical injury were documented in the records
      of health care encounters for syncope for 4.0 percent of all syncopal events and
      6.9 percent of episodes of syncope linked to immunizations. 

PMID- 24299263
TI  - Update: Motor vehicle-related deaths, active and reserve components, U.S. Armed
      Forces, 1999-2012.
AB  - From 1999 to 2012, there were 4,479 motor vehicle accident (MVA)-related deaths
      among members of the U.S. Armed Forces. Of these, the single most common
      underlying cause of death was motorcycle accidents (n=1,134; 25.6%). Among active
      component service members during the 14-year surveillance period, the annual
      number (n=355) and rate (25.1 per 100,000 person-years[p-yrs]) of MVA-related
      deaths peaked in 2004. Since then, a steady downward trend followed and the 2012
      number (n=184) and rate (13.2 per 100,000 p-yrs) were the lowest of the entire
      period. For members of the reserve component, the annual number of deaths peaked
      in 2005 (n=86), but the number in 2012 (n=22) was the lowest of the period. In
      2012, the number (n=90) and rate of deaths (6.5 per 100,000 p-yrs) related to
      motorcycle accidents among active component service members almost equaled the
      number (n=94) and rate of deaths (6.7 per 100,000 p-yrs) from all other types of
      motor vehicle accidents combined. During the entire period, numbers of fatal
      motor vehicle accidents tended to be higher in the warmer months of the year.
      After 2009, motor vehicle accidents were no longer the leading, non-war- related
      cause of death among U.S. service members. 

PMID- 24299264
TI  - Health system composition, rather than labor ward size, should be the basis for
      determining obstetric legal issues.

PMID- 24299266
TI  - Naproxen intercalates with DNA and causes photocleavage through ROS generation.
AB  - Naproxen is an important non-steroidal anti-inflammatory drug with many
      pharmacological and biological properties. In this study, we have attempted to
      ascertain the mode of action and the mechanism of binding of naproxen to DNA. We
      have also demonstrated that, upon irradiation with white light, naproxen
      generates reactive oxygen species, causing DNA cleavage. Generation of reactive
      oxygen species from photo-irradiated naproxen as determined
      spectrophotometrically was found to lead to nicking of plasmid DNA as analyzed by
      agarose gel electrophoresis. Without photo-irradiation, naproxen binds to DNA and
      forms drug-DNA complexes as revealed by spectroscopic techniques. Several
      experiments such as determination of the effect of urea, iodide-induced quenching
      and a competitive binding assay with ethidium bromide showed that naproxen binds
      to DNA primarily in an intercalative manner. These observations were further
      supported by CD analysis, viscosity measurements and molecular docking. Using DNA
      as a template, fluorescence resonance energy transfer between naproxen and
      ethidium bromide was also observed, further strengthening the evidence for
      intercalative binding of naproxen with DNA. 

PMID- 24299267
TI  - Kinetic analysis of cytochrome P450 reductase from Artemisia annua reveals
      accelerated rates of NADH-dependent flavin reduction.
AB  - Cytochrome P450 reductase from Artemisia annua (aaCPR) is a diflavin enzyme that
      has been employed for the microbial synthesis of artemisinic acid (a semi
      synthetic precursor of the anti-malarial drug, artemisinin) based on its ability
      to transfer electrons to the cytochrome P450 monooxygenase, CYP71AV1. We have
      isolated recombinant aaCPR (with the N-terminal transmembrane motif removed) from
      Escherichia coli and compared its kinetic and thermodynamic properties with other
      CPR orthologues, most notably human CPR. The FAD and FMN redox potentials and the
      macroscopic kinetic constants associated with cytochrome c(3+) reduction for
      aaCPR are comparable to that of other CPR orthologues, with the exception that
      the apparent binding affinity for the oxidized coenzyme is ~ 30-fold weaker
      compared to human CPR. CPR from A. annua shows a 3.5-fold increase in uncoupled
      NADPH oxidation compared to human CPR and a strong preference (85 100-fold) for
      NADPH over NADH. Strikingly, reduction of the enzyme by the first and second
      equivalent of NADPH is much faster in aaCPR, with rates of > 500 and 17 s(-1) at
      6  degrees C. We also optically detect a charge-transfer species that rapidly
      forms in < 3 ms and then persists during the reductive half reaction. Additional
      stopped-flow kinetic studies with NADH and (R)-[4-(2) H]NADPH suggest that the
      accelerated rate of flavin reduction is attributed to the relatively weak binding
      affinity of aaCPR for NADP(+) . 

PMID- 24299269
TI  - Time-dependent progression from the acute to chronic phases in atopic dermatitis
      induced by epicutaneous allergen stimulation in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a complicated skin condition influenced by genetic
      background and environmental factors. In this study, we applied Dermatophagoides
      farinae body extract (DfE) to the barrier-disrupted skin of NC/Nga mice twice a
      week for 8 weeks to identify the clinical and immunological factors in AD
      progression. Repeated application of the DfE to the skin of NC/Nga mice showed
      the similar consequences for the natural course of progression in human AD,
      histologically and immunologically. We confirmed that the AD-like skin lesions in
      NC/Nga mice did not last for the whole period of our experiment in spite of
      repeated topical applications of DfE twice a week. Topical DfE stimulation
      increased the skin mRNA expressions of Th1-, Th2- and Th17-related cytokines in
      the acute phase. The expression patterns of IL-4 and IL-13 in splenic T cells and
      skin lesions were consistent with the time course alterations of clinical
      features of AD-like skin symptoms. We also showed that there was a remission
      phase either just before or right after the chronic phase in this experimental
      model. Interestingly, splenic T-cell-derived IL-5 expression began to increase in
      the chronic phase, while skin-derived IL-5 mRNA expression increased in the acute
      phase. In conclusion, our results suggest that we should pay attention to the
      characteristics of each stage of AD progression and choose a suitable
      corresponding stage of animal model not only to elucidate the pathogenesis of AD
      but also to develop and evaluate therapeutic drugs for AD. 

PMID- 24299270
TI  - Mechanism of ion transfer in supported liquid membrane systems: electrochemical
      control over membrane distribution.
AB  - A polarization study carried out on a thin supported liquid membrane separating
      two aqueous compartments is presented. Transfer of both the ionized and uncharged
      form of an organic tracer dye, rhodamine B ([9-(2-carboxyphenyl)-6-diethylamino-3
      xanthenylidene]-diethylammonium chloride), across supported liquid membranes
      composed of one of 1-octanol (octan-1-ol), 1,9-decadiene (deca-1,9-diene), 1,2
      dichlorobenzene, or nitrophenyl octyl ether (1-(2-nitrophenoxy)octane) was
      studied using cyclic voltammetry and UV-vis absorption spectrophotometry.
      Concentration analysis indicates that the high membrane concentration of
      rhodamine B determines the ionic transfer observed via voltammetry, which is
      consistent with the low aqueous ionic concentration and large membrane/aqueous
      distribution of the molecule. The observed double-transfer voltammogram, although
      it has been largely neglected in previous literature, is a logical consequence of
      the presence of two liquid-liquid interfaces and is rationalized in terms of ion
      transfer across the two interfaces on either side of the membrane and supported
      by voltammograms obtained for a series of ions of varied lipophilicity. The
      bipolar nature of the voltammetric response offers an effective way of mass
      transport control via changing polarity of the applied voltage and finds
      immediate use in extraction, purification, and separation applications. 

PMID- 24299271
TI  - Classical trajectory study of energy transfer in collisions of highly excited
      allyl radical with argon.
AB  - Predicting the results of collisions of polyatomic molecules with a bath of atoms
      is a research area that has attracted substantial interest in both experimental
      and theoretical chemistry. Energy transfer, which is the consequence of such
      collisions, plays an important role in gas-phase kinetics and relaxation of
      excited molecules. We present a study of energy transfer in single collisions of
      highly vibrationally excited allyl radical in argon. We evolve a total of 52 000
      classical trajectories on a potential energy surface, which is the sum of an ab
      initio intramolecular potential for the allyl and a pairwise interaction
      potential describing the argon's effect on the allyl. The former is described by
      means of a permutationally invariant full-dimensional potential, whereas the
      interaction potential between allyl and argon is obtained by means of a sum of
      pairwise potentials dependent on nonlinear parameters that have been fit to a set
      of MP2/avtz counterpoise corrected ab initio energies. Results are reported for
      energy transfers and related probability densities at different collisional
      energies. The sensitivity of results to the interaction potential is considered
      and the potential is shown to be suitable for future applications involving
      different isomers of the allyl. The impact of highly efficient collisions in the
      energy transfer process is examined. 

PMID- 24299272
TI  - Characterizing slow chemical exchange in nucleic acids by carbon CEST and low
      spin-lock field R(1rho) NMR spectroscopy.
AB  - Quantitative characterization of dynamic exchange between various conformational
      states provides essential insights into the molecular basis of many regulatory
      RNA functions. Here, we present an application of nucleic-acid-optimized carbon
      chemical exchange saturation transfer (CEST) and low spin-lock field R(1rho)
      relaxation dispersion (RD) NMR experiments in characterizing slow chemical
      exchange in nucleic acids that is otherwise difficult if not impossible to be
      quantified by the ZZ-exchange NMR experiment. We demonstrated the application on
      a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and
      R(1rho) RD profiles of base and sugar carbons revealed slow exchange dynamics
      involving a sparsely populated (p ~ 10%) and shortly lived (tau ~ 10 ms) NMR
      "invisible" state. The utility of CEST and low spin-lock field R(1rho) RD
      experiments in studying slow exchange was further validated in characterizing an
      exchange as slow as ~60 s(-1).

PMID- 24299273
TI  - Cellular toxicity associated with exposure to perfluorinated carboxylates (PFCAs)
      and their metabolic precursors.
AB  - The biotransformation of fluorotelomer based compounds yields saturated and
      unsaturated fluorotelomer aldehydes (FTALs and FTUALs, respectively) and
      carboxylic acids (FTCAs and FTUCAs, respectively) as intermediate metabolites
      that subsequently transform to perfluorinated carboxylic acids (PFCAs). Previous
      studies have demonstrated that the FTCAs and FTUCAs are 1 to 5 orders of
      magnitude more toxic than PFCAs after exposure to aquatic organisms.
      Additionally, FTUALs have demonstrated reactivity with proteins, which may be
      associated with toxicity through the inhibition of protein function. The purpose
      of this study was to carry out a comprehensive assessment of the relative
      toxicity between PFCAs and their intermediate precursor metabolites: the FTALs,
      FTUALs, FTCAs, and FTUCAs. Analytes were separately incubated with human liver
      epithelial (THLE-2) cells to assess how varying the functional group and the
      fluorinated chain length affects cell viability. For each analyte, dose-response
      EC50 values were calculated. The EC50 values for FTUCAs and FTCAs were similar,
      with values ranging from 22 +/- 9 and 24 +/- 9 MUM for the 10:2 congeners to 1004
      +/- 20 and 1004 +/- 24 MUM for the 4:2 congeners, respectively. The EC50 values
      for the PFCAs ranged from 65 +/- 41 (PFDA) to 1361 +/- 146 (PFBA) MUM. The range
      of toxicity between PFCAs and their acid precursors were similar. However, the
      comparative toxicity between the 6:2 and 8:2 congeners and their corresponding
      PFCA had toxicity thresholds that varied depending on the functional headgroup,
      where FTUALs >= FTALs > FTUCAs >= FTCAs > PFCAs. For all PFCAs and acid
      precursors, toxicity depended on the length of the fluorinated chain, where the
      longer chain lengths yielded greater bioaccumulation and enhanced toxicity,
      results which agreed with those previously reported. By contrast, FTALs and
      FTUALs were the most toxic of all the analytes examined, where toxicity was
      enhanced at shorter chain lengths, with EC50 values of 7 +/- 1 MUM (6:2 FTUAL)
      and 8.6 +/- 0.8 MUM (6:2 FTAL). DNA adducts were not detectable for the aldehyde
      precursors, using a quantitative long-range PCR method. Our data provide the
      first evidence that aldehyde intermediates have demonstrated toxicity in cellular
      systems that is more significant than PFCAs and their corresponding acid
      intermediates. 

PMID- 24299274
TI  - Fabrication of a detection platform with boronic-acid-containing zwitterionic
      polymer brush.
AB  - Development of technologies for biomedical detection platform is critical to meet
      the global challenges of various disease diagnoses, especially for point-of-use
      applications. Because of its natural simplicity, effectiveness, and easy
      repeatability, random covalent-binding technique is widely adopted in antibody
      immobilization. However, its antigen-binding capacity is relatively low when
      compared to site-specific immobilization of antibody. Herein, we report that a
      detection platform modified with boronic acid (BA)-containing sulfobetaine-based
      polymer brush. Mainly because of the advantage of oriented immobilization of
      antibody endowed with BA-containing three-dimensional polymer brush architecture,
      the platform had a high antigen-binding capacity. Notably, nonspecific protein
      adsorption was also suppressed by the zwitterionic pendants, thus greatly
      enhanced signal-to-noise (S/N) values for antigen recognition. Furthermore,
      antibodies captured by BA pendants could be released in dissociation media. This
      new platform is promising for potential applications in immunoassays. 

PMID- 24299275
TI  - Campylobacter jejuni prevalence and hygienic quality of retail bovine ground meat
      in Finland.
AB  - Detection of common genotypes of Campylobacter jejuni among Finnish human and
      bovine isolates, suggested that bovines may be a source for zoonotic Camp. jejuni
      infection. In addition, a Finnish epidemiological study implied the tasting and
      eating raw or undercooked beef as risk factors for acquiring campylobacteriosis.
      We therefore performed a study on the occurrence of Camp. jejuni in retail bovine
      ground meat in Helsinki by the use of both cultivation and PCR. During 2011 and
      2012, 175 bovine ground meat samples were collected. None of the samples were
      Campylobacter positive by cultivation, and only one sample (0.6%) was Camp.
      jejuni positive by the use of PCR on template extracted directly from ground
      meat. According to our findings, Finnish bovine ground meat is an unlikely source
      for human campylobacteriosis. Additionally, the hygienic quality of bovine ground
      meat at retail level was screened and found to be good when monitored by aerobic
      micro-organisms, total thermotolerant coliforms and Eshericha coli. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study provides the first data on the occurrence of
      the zoonotic pathogen Campylobacter jejuni in Finnish bovine ground meat. This
      knowledge is important as part of future Campylobacter risk assessment,
      management and monitoring programs, particularly when assessing the relative
      attribution of poultry, pork and bovine meat to the burden of human
      campylobacteriosis. According to our results, Finnish bovine ground meat at
      retail level is of good hygienic quality.

PMID- 24299276
TI  - A randomized controlled trial of a video module to increase U.S. poison center
      use by low-income parents.
AB  - CONTEXT: U.S. poison centers decrease medical visits by providing telephone
      advice for home management of potential poisonings, but are underutilized by low
      income African-American and Latino parents, and those with limited English
      proficiency, due to lack of knowledge and misconceptions about poison centers.
      OBJECTIVES: To assess the effectiveness of a poison prevention video module in
      improving knowledge, behavior, and behavioral intention concerning use of poison
      centers in a population of low-income, language-diverse adults attending
      parenting courses offered by a community organization. METHODS: A randomized,
      blinded, controlled trial was conducted at 16 parenting course sites of a
      community organization and included 297 participants. The organization's
      instructors presented the video module (intervention) or the usual class
      curriculum (control). Participants completed questionnaires at baseline and a
      telephone interview 2-4 weeks later. Changes from baseline to follow-up were
      compared between the intervention and control groups using analysis of variance
      and Chi-square tests. Intervention group participants were stratified by English
      proficiency and compared to assess baseline and follow-up responses by language.
      RESULTS: After the intervention, participants in the intervention group had a
      significantly greater increase in knowledge about the poison center, were more
      likely to have the correct poison center phone number at home, and had greater
      behavioral intention to use the poison center compared to control group
      participants. At baseline, Spanish-primary-language participants with limited
      English proficiency had less knowledge about the poison center, were less likely
      to have the poison center number at home, and had lower behavioral intention to
      use the poison center than English proficient participants, but significantly
      improved after the intervention. CONCLUSIONS: This video module, when presented
      by a community organization's instructors, was highly effective in improving
      knowledge, behavior, and behavioral intention concerning use of poison centers
      within a low-income, language-diverse population.

PMID- 24299277
TI  - Incidence of clinically silent malrotation detected on barium swallow examination
      in children.
AB  - INTRODUCTION: Duodenojejunal flexure (DJF) orientation is often examined
      routinely during contrast swallow studies, including those performed for purely
      oesophageal queries. We examine the radiation burden and the incidence of
      malrotation in patients undergoing contrast swallow, without clinical suspicion
      for malrotation. METHODS: Two hundred eighteen consecutive contrast swallow
      studies were reviewed. Patients whose history may potentially suggest malrotation
      were identified (n = 90), and remaining children were grouped based on whether
      DJF was examined (Group 1; n = 88) or not (Group 2; n = 40). Data extracted
      include demographics, radiographic parameters (dosage, screening time, number of
      images obtained) and examination findings. Outcome measures comprised: (i)
      prevalence of clinically incidental malrotation; and (ii) influence of additional
      evaluation of DJF on patient dosage (mean +/- SEM). RESULTS: Malrotation was
      identified in 2 of 90 patients (2.2%) examined with clinical indications for
      possible malrotation, but none in Group 1 (13% already had normal DJF confirmed
      on previous examinations). Groups 1 and 2 were comparable with respect to age and
      gender (P = ns). Additional evaluation of DJF (Group 1) meant that 54% more
      images were acquired (48.5 +/- 2.9 vs. 31.4 +/- 3.4 images in group 2; P =
      0.0002) and 24.9% increased screening time (130.8 +/- 9.3 vs. 104.7 +/- 13.0
      seconds in group 2; P = 0.089), resulting in 32.6% increased patient dosage (1.36
      +/- 0.21 vs. 1.02 +/- 0.16 microGym(2) /kg in group 2; P = 0.19). CONCLUSIONS:
      This study highlights the increased radiation exposures involved with routine
      screening for DJF position in those patients without clinical suspicion of
      malrotation, and raises questions about the validity of this practice; however,
      further research is needed.

PMID- 24299279
TI  - Mechanistic insights into the C-H bond activation of hydrocarbons by chromium(IV)
      oxo and chromium(III) superoxo complexes.
AB  - The mechanism of the C-H bond activation of hydrocarbons by a nonheme
      chromium(IV) oxo complex bearing an N-methylated tetraazamacrocyclic cyclam (TMC)
      ligand, [Cr(IV)(O)(TMC)(Cl)](+) (2), has been investigated experimentally and
      theoretically. In experimental studies, reaction rates of 2 with substrates
      having weak C-H bonds were found to depend on the concentration and bond
      dissociation energies of the substrates. A large kinetic isotope effect value of
      60 was determined in the oxidation of dihydroanthracene (DHA) and deuterated DHA
      by 2. These results led us to propose that the C-H bond activation reaction
      occurs via a H-atom abstraction mechanism, in which H-atom abstraction of
      substrates by 2 is the rate-determining step. In addition, formation of a
      chromium(III) hydroxo complex, [Cr(III)(OH)(TMC)(Cl)](+) (3), was observed as a
      decomposed product of 2 in the C-H bond activation reaction. The Cr(III)OH
      product was characterized unambiguously with various spectroscopic methods and X
      ray crystallography. Density functional theory (DFT) calculations support the
      experimental observations that the C-H bond activation by 2 does not occur via
      the conventional H-atom-abstraction/oxygen-rebound mechanism and that 3 is the
      product formed in this C-H bond activation reaction. DFT calculations also
      propose that 2 may have some Cr(III)O(*-) character. The oxidizing power of 2 was
      then compared with that of a chromium(III) superoxo complex bearing the identical
      TMC ligand, [Cr(III)(O2)(TMC)(Cl)](+) (1), in the C-H bond activation reaction.
      By performing reactions of 1 and 2 with substrates under identical conditions, we
      were able to demonstrate that the reactivity of 2 is slightly greater than that
      of 1. DFT calculations again support this experimental observation, showing that
      the rate-limiting barrier for the reaction with 2 is slightly lower than that of
      1. 

PMID- 24299278
TI  - Chagas disease-specific antigens: characterization of epitopes in CRA/FRA by
      synthetic peptide mapping and evaluation by ELISA-peptide assay.
AB  - BACKGROUND: The identification of epitopes in proteins recognized by medically
      relevant antibodies is useful for the development of peptide-based diagnostics
      and vaccines. In this study, epitopes in the cytoplasmic repetitive antigen (CRA)
      and flagellar repetitive antigen (FRA) proteins from Trypanosoma cruzi were
      identified using synthetic peptide techniques and pooled sera from Chagasic
      patients. The epitopes were further assayed with an ELISA assay based on
      synthetic peptides. METHODS: Twenty-two overlapping synthetic peptides
      representing the coding sequence of the T. cruzi CRA and FRA proteins were
      assessed by a Spot-synthesis array analysis using sera donated by patients with
      Chagas disease. Shorter peptides were selected that represented the determined
      epitopes and synthesized by solid phase synthesis to evaluate the patterns of
      cross-reactivities and discrimination through an ELISA-diagnostic assay. RESULTS:
      The peptide Spot-synthesis array successfully identified two IgG antigenic
      determinants in the CRA protein and four in FRA. Bioinformatics suggested that
      the CRA antigens were unique to T. cruzi while the FRA antigen showed similarity
      with sequences present within various proteins from Leishmania sp. Subsequently,
      shorter peptides representing the CRA-1, CRA-2 and FRA-1 epitopes were
      synthesized by solid phase synthesis and assayed by an ELISA-diagnostic assay.
      The CRA antigens gave a high discrimination between Chagasic, Leishmaniasis and
      T. cruzi-uninfected serum. A sensitivity and specificity of 100% was calculated
      for CRA. While the FRA antigen showed a slightly lower sensitivity (91.6%), its
      specificity was only 60%. CONCLUSIONS: The epitopes recognized by human anti-T.
      cruzi antibodies have been precisely located in two biomarkers of T. cruzi, CRA
      and FRA. The results from screening a panel of patient sera through an ELISA
      assay based on peptides representing these epitopes strongly suggest that the
      sequences from CRA would be useful for the development of diagnostic reagents
      that could improve upon the sensitivity and specificity of currently available
      diagnostic tests. Overall, the results provide further evidence of the usefulness
      of identifying specific linear B-cell epitopes for improving diagnostic tools.

PMID- 24299280
TI  - Chagas disease in Australia and New Zealand: risks and needs for public health
      interventions.
AB  - OBJECTIVE: International migration has changed the global distribution of Chagas
      disease, with the emerging importance of non-endemic regions. We aimed at better
      documenting the Australia and New Zealand risk of Chagas disease and needs for
      interventions. METHODS: We reviewed Chagas disease-related evidences, policies
      and practices in Australia and New Zealand and calculated the estimated
      prevalence. RESULTS: Australia hosts a rapidly growing population at risk and had
      1928 infected residents in 2011; New Zealand had 98 in 2006. These figures
      underestimate the real situation, as they do not consider non-permanent
      residents. The only existing policy in both countries is the identification of
      blood donors with a history of or a risk of infection via questionnaire. There is
      no programme of detection and care of patients. The lifetime economic burden of
      disease for society is potentially very high. CONCLUSION: Chagas disease is an
      emerging health risk with potential high human and economic costs in Australia
      and New Zealand in the absence of public health attention. Implementing
      strategies to screen high-risk groups and prevent transmission should be
      considered. Moreover, migration between the Western Pacific and Chagas endemic
      regions and the presence of vectors means this risk applies in the whole region.

PMID- 24299282
TI  - Asking only "Did you use a condom?" underestimates the prevalence of unprotected
      sex among perinatally HIV infected and perinatally exposed but uninfected youth.
AB  - Among young adults who use condoms, incomplete condom use (putting a condom on
      after beginning or taking a condom off before finishing sex) and condom failure
      (condom breaking or slipping off during sex) are common. Therefore, sexual
      behavior surveys that ask only if a condom was used are likely to underestimate
      the actual prevalence of unprotected sex. This study examined data from 135
      sexually active perinatally HIV-infected (PHIV+) youth and perinatally exposed
      but uninfected (PHIV-) youth, ages 13 to 24. Participants were asked whether they
      used a condom on their first and their most recent occasion of vaginal sex. Youth
      who reported using a condom were asked a follow-up question about whether there
      was any time during that occasion when sex was not protected by a condom. This
      follow-up question identified additional participants--almost double the
      proportions who initially said they did not use a condom--who had unprotected
      sex. Incomplete condom use was similar among PHIV+ and PHIV-youth, boys and
      girls, Latinos and African Americans, and younger and older youth. These findings
      illustrate the importance of asking specifically about whether any unprotected
      behavior occurred from start to finish of sex to achieve more valid estimates of
      sexual risk behavior.

PMID- 24299283
TI  - Effects of epilepsy treatments on sleep architecture and daytime sleepiness: an
      evidence-based review of objective sleep metrics.
AB  - OBJECTIVE: Sleep is considered restorative, and good quantity and quality sleep
      is required for memory consolidation and synaptic plasticity. Sleep disorders are
      common in patients with epilepsy. Poor sleep quality or quantity may worsen
      seizure control. On the other end, seizures and epilepsy may worsen the sleep
      quality and set a vicious cycle. In addition, antiepileptic drugs have an effect
      on sleep architecture. We performed a systemic literature review with a goal to
      evaluate the effect of antiepileptic drugs and nondrug treatments for epilepsy on
      sleep architecture to help better understand treatment effects, especially in
      patients with epilepsy and sleep problems. METHODS: We searched PubMed and
      identified studies that evaluated objective sleep outcomes for an antiepileptic
      drug. We also searched for studies with objective sleep outcomes that evaluated
      other epilepsy treatments such as epilepsy surgery, vagus nerve stimulation, and
      ketogenic diet. RESULTS: The studies were categorized based on evidence class and
      study population for an individual antiepileptic drug or treatment. We identified
      that most antiepileptic drugs and nondrug treatments for epilepsy affect sleep
      architecture. SIGNIFICANCE: We identified that gabapentin, tiagabine, pregabalin,
      clobazam, and carbamazepine reduce sleep latency and/or improve sleep efficiency.
      Phenobarbital, valproic acid, and higher-dose levetiracetam aggravate daytime
      sleepiness, whereas topiramate and zonisamide do not. Vagus nerve stimulation
      reduces daytime sleepiness, and ketogenic diet improves slow-wave sleep. Epilepsy
      surgery may improve nocturnal sleep only in a subgroup of patients with improved
      seizure frequency. Further studies are needed to evaluate the dose-dependent
      sleep effects of antiepileptic drugs and nondrug treatments independent of the
      improvement of epilepsy, and to identify if these changes are clinically
      significant.

PMID- 24299281
TI  - The proper criteria for identification and sorting of very small embryonic-like
      stem cells, and some nomenclature issues.
AB  - Evidence has accumulated that both murine and human adult tissues contain early
      development stem cells with a broader differentiation potential than other adult
      monopotent stem cells. These cells, being pluripotent or multipotent, exist at
      different levels of specification and most likely represent overlapping
      populations of cells that, depending on the isolation strategy, ex vivo expansion
      protocol, and markers employed for their identification, have been given
      different names. In this review, we will discuss a population of very small
      embryonic-like stem cells (VSELs) in the context of other stem cells that express
      pluripotent/multipotent markers isolated from adult tissues as well as review the
      most current, validated working criteria on how to properly identify and isolate
      these very rare cells. VSELs have been successfully purified in several
      laboratories; however, a few have failed to isolate them, which has raised some
      unnecessary controversy in the field. Therefore, in this short review, we will
      address the most important reasons that some investigators have experienced
      problems in isolating these very rare cells and discuss some still unresolved
      challenges which should be overcome before these cells can be widely employed in
      the clinic.

PMID- 24299284
TI  - [Multiple endocrine neoplasia type 1 syndrome with special emphasis on
      pancreatoduodenal tumours--a case report analysis].
AB  - INTRODUCTION: The syndrome of multiple endocrine neoplasia type 1 (MEN 1) is a
      relatively rare hereditary disease predisposing to a variety of tumours, some of
      which may be hormonally active. The main organs affected are the parathyroid, the
      pituitary and the pancreatoduodenal area. Despite the rarity of MEN 1, its
      occurrence is not negligible in clinical practice and the clinicians ignorance
      often leads to delayed diagnosis and inadequate treatment. MATERIAL AND METHODS:
      The aim of this review is to present contemporary literature on this issue,
      including the most controversial topic, i.e. recent modalities of treatment of
      pancreatoduodenal tumours, and to present a case report. The literature review
      was based on computer searches in PubMed and DynaMed. DISCUSSION:
      Pancreatoduodenal tumours associated with MEN 1 are relatively slow-growing
      neoplasias. The development of liver metastases is the main factor of long-term
      survival. The aim of surgical treatment is the stabilisation of the disease and
      the prevention of liver metastases. Radical surgical methods may lead to better
      biochemical curability. The extent of surgical intervention should be selected
      individually. We discuss our case report in the context of these findings.
      CONCLUSION: Knowledge of the MEN 1 syndrome has its importance in the clinical
      practice. Further prospective studies will be needed to evaluate the
      effectiveness of treatment, especially for pancreatoduodenal tumours.

PMID- 24299285
TI  - [Laparoscopic lavage and drainage in the management of acute diverticulitis: is
      it time to move on?].
AB  - INTRODUCTION: Diverticular disease management represents a very topical issue
      with many unanswered questions as yet. Laparoscopic lavage and drainage in
      patients with acute diverticulitis is one of the controversial areas.
      Miniinvasive approach presents a possible treatment alternative for CT-guided
      percutaneous drainage and also for radical colon resection in the form of
      Hartmanns procedure or resection with primary anastomosis. MATERIAL A METHODS:
      The authors aim was the evaluation of patients with Hinchey II, III or IV
      diverticulitis treated by laparoscopic lavage and drainage, or by laparoscopic
      suture of the perforation, in a retrospective cohort study. The inclusion
      criterion for the study was laparoscopic lavage and drainage indication in
      patients with Hinchey II, III or IV diverticulitis. The primary aim of the study
      was laparoscopic treatment evaluation focused on leakage, if applicable, and on
      postoperative morbidity and mortality. RESULTS: During the study period (2007
      2012), 12 patients operated on at our department (with a mean age of 71.7 years)
      were included into the study. The group comprised 7 men and 5 women with a BMI of
      28.1 kg/m2. Laparoscopic exploration, lavage and drainage of the abdominal cavity
      with purulent peritonitis finding were performed in 10 patients. The site of
      bowel perforation was not located unambiguously in these patients. Two patients
      with faecal peritonitis and identified place of perforation underwent
      laparoscopic lavage, drainage and suture of the perforation. Postoperative
      leakage was not detected in any of the patients. The mean operating time was 65
      minutes, postoperative morbidity reaching 27.7%, and postoperative mortality 0%.
      The mean length of hospital stay was 8.8 days. Elective laparoscopic resection
      was performed 6-15 weeks after the primary operation in 8 patients. CONCLUSION:
      Laparoscopic exploration with thorough lavage, suture of the perforation and
      drainage presents a possible alternative in modern management of acute
      diverticulitis. The miniinvasive approach indication should be based both on
      careful, highly individualised and complex patient evaluation and on the
      departments experience.

PMID- 24299286
TI  - [Reconstruction of complex abdominal wall defects using the component separation
      technique].
AB  - INTRODUCTION: Reconstruction of complex abdominal wall defects is among the most
      demanding procedures in reconstructive surgery. Introduction of the method of
      component separation represents the most significant advance in the care of these
      patients. We present our experience with the component separation technique on a
      series of 44 patients. MATERIALS AND METHODS: We retrospectively reviewed
      patients operated on between 2009 and 2012. The inclusion criterion was the use
      of the component separation technique in the treatment of abdominal wall defect.
      The scoring criteria were recurrent hernia, wound hematoma, wound infection, skin
      necrosis and secondary healing. RESULTS: We operated on 44 patients in the above
      period. The etiology of the defects was most frequently hernia in the scar after
      midline laparotomy (n = 29; 66%) and after incision across the epigastrium for
      total gastrectomy (n = 3; 7%). The other defects (n = 12; 27%) were caused by a
      wide diastasis of the abdominal rectus muscles (width 8-10 cm). The most common
      complication was a hematoma in the lateral part of the wound which occurred in 7
      patients (16%). We did not detect any hernia recurrence in the original abdominal
      wall defects. CONCLUSION: The method of components separation allows us to stitch
      the edges of the full-thickness abdominal wall to each other, even in cases of
      large hernias. The introduction of this technique into practice has reduced the
      risk of recurrence of large hernias without a significant increase in
      postoperative complications.

PMID- 24299287
TI  - [Minimally invasive video-assisted operations for heart disease].
AB  - INTRODUCTION: Minimally invasive surgical access for the treatment of mitral and
      tricuspid valves has become an alternative method to the conventional approach
      via median sternotomy. The aim of this paper is to evaluate our experience and
      results with minimally invasive approach in cardiac surgery at our institution.
      MATERIAL AND METHODS: A total of 52 patients underwent minimally invasive cardiac
      surgery between November 2011 and March 2013. Right lateral minithoracotomy and
      femoral vessels cannulation for cardiopulmonary bypass was used. Follow-up data
      was collected in a prospective database and analysed retrospectively. RESULTS:
      The mean age of patients was 60.9 +/- 11.6 years (female patients accounted for
      63.5%). The procedures performed included mitral valve repair in 44 (85%)
      patients and tricuspid valve repair in 25 (48%). Atrial septal defect closure was
      performed in 8 (15%) patients and cryoablation of atrial fibrillation in 26 (50%)
      patients. There were 75% combined procedures. The median duration of the
      operation was 235 (155-315) minutes. The median length of cardiopulmonary bypass
      and crossclamp time was 139 (89-225) and 92 (51-168) minutes, respectively. The
      median duration of postoperative hospital stay was 12.5 (6-34) days. Hospital and
      30-day mortality was 0%. At follow-up (121.3 +/- 32.72 days), two patients (3.8%)
      required reoperation (1 for right haemothorax, 1 for aortic valve insufficiency).
      CONCLUSION: Minimally invasive access has been adopted as a routine method for
      the therapy of valve disease. The minithoracotomy approach is a safe and feasible
      technique with comparable mortality and in-hospital morbidity.

PMID- 24299288
TI  - [Heparin-induced thrombocytopenia in a patient with acute thrombosis, acute
      aortic dissection and acute lower limb ischaemia].
AB  - This case report presents the course of illness, as well as the diagnosis and
      therapy, of acute thrombosis and abdominal aortic dissection after Fogarty
      thrombectomy with the symptoms of acute limb ischaemia in a 42-year-old female
      patient suffering from heparin-induced thrombocytopenia. HIT is a severe
      iatrogenic complication emerging after unfractionated or low molecular weight
      heparin administration, with rather easy diagnosis; however, it is often
      neglected due to the rarity of its occurrence.

PMID- 24299289
TI  - [Difficult differential diagnosis of malignant melanoma--case reports].
AB  - Malignant melanoma is one of the most malignant tumours. If it is diagnosed in
      the early stage, the prognosis is quite good. Timely diagnosis is essential as
      well as early surgical removal of the tumour in a specialized centre. The aim of
      the article is to highlight the difficult diagnosis and differential diagnosis of
      malignant melanoma. The authors describe a rare case of malignant melanoma in an
      eleven-year-old girl, a neglected finding of malignant melanoma in a young man,
      the difficult differential diagnosis of malignant melanoma and a case of
      malignant melanoma arising from a congenital naevus.The incidence of malignant
      melanoma is increasing worldwide, and it is therefore necessary to bear this
      diagnosis in mind when performing clinical examination of patients and
      discovering suspected lesions.

PMID- 24299290
TI  - [Chest drainage--physiological and pathophysiological aspects and indications].
AB  - INTRODUCTION: Interventions in the chest region still remain a source of concern
      for the medical community. Surgeons in particular, however, should be well
      familiar with this technique as it is them who perform the majority of these
      drainages. OBJECTIVE: The aim of the article is to give an outline of the
      physiology and pathophysiology of respiration in relation to the chest drainage
      indication, and to discuss the different indications for this type of drainage.
      CONCLUSION: Chest drainage is, in case of correct indication and performance, a
      safe method of therapy for a number of pleural pathologies. It is necessary to
      consider its employment on a case-by-case basis because it is always essential to
      assess its benefits versus risks.

PMID- 24299291
TI  - [Chest drainage methods. The work is intended for postgraduate medical
      education].
AB  - INTRODUCTION: The mastering of the chest drainage technique should be among the
      basic skills of any surgeon, pneumologist or critical care specialist. What is
      essential is the knowledge of the anatomy of the chest, the basic radiologic
      interpretation of pathological findings in the pleural cavity, and some manual
      skill. The possibility of complications occurring and the method of their
      treatment are also important. OBJECTIVE: The aim of the article is to give an
      outline of the time aspect of the indication, necessary material equipment, the
      technique of chest drainage itself, differences in the drainage of pneumothorax,
      free and circumscribed effusion, caring for the chest drain following drainage
      and also of possible errors and mistakes that may occur. It also deals with
      methods of solving the complications. CONCLUSION: Chest drainage performed by a
      physician experienced in the chest drainage technique and keeping its basic
      principles may be considered to be a safe and effective method.

PMID- 24299292
TI  - [Chest drainage systems and the complications associated with drainage].
AB  - INTRODUCTION: Chest drainage inevitably involves attaching the drain to a chest
      drainage system. Chest drainage may be related to some specific complications.
      OBJECTIVE: The aim of the article is to explain the classification and principles
      of the individual chest drainage systems. They may be divided into passive ones
      (valve and water seal) and active chest suction. Balanced chest drainage
      represents a specific method. Further, the article deals with the most common
      complications of chest drainage, namely prolonged air leak, multifactorial lung
      oedemas, atrial fibrillation and empyema of the chest cavity. CONCLUSION: The
      choice of a suitable drainage system is an important factor for the success of
      chest drainage, including the probability of complications occurring. The
      knowledge of appropriate methods of solving the complications of chest drainage,
      including the use of less standard techniques, allows us to treat the majority of
      even considerably complicated conditions.

PMID- 24299293
TI  - Changes in the physical functions of pre-frail elderly women after participation
      in a 1-year preventative exercise program.
AB  - AIM: The present study clarifies the effects of participation in a preventative
      health classroom program (exercise program) for 1 year on the physical functions
      of pre-frail elderly individuals in comparison with healthy elderly individuals.
      METHODS: Participants in the study included 28 elderly pre-frail female
      participants and 28 elderly healthy female participants. Participants engaged in
      the exercise program for 1 year. There was no significant age or physical
      differences between both groups. Before and after the exercise program, the
      following physical function tests were carried out: grip strength, one-legged
      balance with eyes open, 5-m walking time and a timed up & go (TUG). RESULTS: The
      pre-frail elderly group tested significantly lower in the one-legged balance with
      eyes open test and the TUG test compared with the healthy elderly group. The 5-m
      walking time test improved significantly in both groups, but the TUG improved
      only in the pre-frail elderly group. Conversely, the grip strength and one-legged
      balance with eyes open tests remained unchanged. CONCLUSION: Improvements in the
      TUG and 5-m walking time tests were found in the pre-frail elderly group after
      the 1-year exercise program. Their results in the TUG test might be greater than
      those among the healthy elderly individuals.

PMID- 24299294
TI  - Reply: Methods of holding the cervix and applying compression based on uterine
      bleeding: caudal or cephalad to the uterus?

PMID- 24299295
TI  - Promoter-associated histone acetylation is involved in the osmotic stress-induced
      transcriptional regulation of the maize ZmDREB2A gene.
AB  - Epigenetic modifications play a key role in the transcriptional regulation of
      stress-induced gene expression in plants. In this study, we showed that the
      overall acetylation levels of histone H3 lysine 9 (H3K9) and H4 lysine 5 (H4K5)
      in the genome were increased in maize seedlings after mannitol treatment (to
      mimic osmotic stress). Mannitol treatment significantly induced the upregulation
      of the maize osmotic stress responsive gene Zea mays dehydration-responsive
      element binding protein 2A (ZmDREB2A), whereas abscisic acid (ABA) did not result
      in the induction of this gene. The application of exogenous ABA under osmotic
      stress conditions strongly repressed the induction of the ZmDREB2A gene.
      Chromatin immunoprecipitation and chromatin accessibility by real-time PCR
      experiments revealed that the promoter region of the ZmDREB2A gene was quickly
      hyperacetylated and decondensed after the mannitol treatment, suggesting that the
      promoter region is poised for histone acetylation to allow for fast induction of
      the ZmDREB2A gene. However, under osmotic stress conditions, the ABA treatment
      decreased the acetylation status and chromatin accessibility to micrococcal
      nuclease. These results suggest that osmotic stress activates the transcription
      of the ZmDREB2A gene by increasing the levels of acetylated histones H3K9 and
      H4K5 associated with the ZmDREB2A promoter region. 

PMID- 24299296
TI  - Cystic endosalpingiosis presenting as chronic back pain, a case report.
AB  - A 48-year old woman presented with chronic back pain. Previous examinations had
      been inconclusive. Gynaecological examination revealed large cystic masses on the
      fundus uteri and left adnexa. Laparoscopy and histopathology showed unusually
      extensive cystic endosalpingiosis covering the serosa-coated uterine surface as
      well as the adnexa on both sides. After uneventful laparoscopic-assisted vaginal
      hysterectomy the patient quickly recovered and was relieved of her chronic
      backache. Virtual slides:
      http://www.diagnosticpathology.diagnomx.eu/vs/1501709091077524.

PMID- 24299297
TI  - Structural analysis of Mycobacterium tuberculosis ATP-binding cassette
      transporter subunit UgpB reveals specificity for glycerophosphocholine.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most
      devastating human diseases, and is responsible for ~ 2 million deaths worldwide
      each year. The nutritional requirements for the growth of mycobacteria have been
      extensively studied since the discovery of M. tuberculosis, but the essential
      nutrients for M. tuberculosis inside the human host and the identity of the
      corresponding transporters remain unknown. The UgpABCE transporter of M.
      tuberculosis is one of five putative permeases for carbohydrate uptake, and is
      genetically predicted to be an sn-glycerol 3-phosphate importer. We have
      determined the 1.5-A crystal structure of M. tuberculosis UgpB, which has been
      reported to be a promising vaccine candidate against TB. M. tuberculosis UgpB
      showed no detectable binding activity for sn-glycerol 3-phosphate by isothermal
      titration calorimetry, but instead showed a preference for glycerophosphocholine
      (GPC). M. tuberculosis UgpB largely resembles its Escherichia coli homolog, but
      with the critical Trp169 in the substrate-binding site of E. coli UgpB replaced
      by Leu205. Mutation of Leu205 abolishes GPC binding, suggesting that Leu205 is a
      determinant of GPC binding. The work reported here not only contributes to our
      understanding of the carbon and phosphate sources utilized by M. tuberculosis
      inside the human host, but will also promote improvements in TB chemotherapy.
      DATABASE: Structural data are available in the Protein Data Bank database under
      the accession number PDB 4MFI.

PMID- 24299298
TI  - Incidence, trends and demographics of Staphylococcus aureus infections in
      Auckland, New Zealand, 2001-2011.
AB  - BACKGROUND: New Zealand has a higher incidence of Staphylococcus aureus disease
      than other developed countries, with significant sociodemographic variation in
      incidence rates. In contrast to North America, the majority of disease is due to
      methicillin-susceptible S. aureus (MSSA), although relatively little is known
      about the comparative demographics of MSSA and methicillin-resistant S. aureus
      (MRSA) infections in New Zealand. METHODS: Our objectives were to describe the
      trends, incidence and patient demographics of all S. aureus infections in
      patients presenting to our institution between 2001 and 2011, and compare the
      epidemiology of MSSA and MRSA infections. We identified all patients with S.
      aureus infections over the study period. A unique S. aureus infection was defined
      as the first positive S. aureus culture taken from the same patient within a
      thirty-day period. Standard definitions were used to classify episodes into
      community- or healthcare-associated S. aureus infection. RESULTS: There were
      16,249 S. aureus infections over the study period. The incidence increased
      significantly over the study period from 360 to 412 per 100,000 population (P <
      0.001), largely driven by an increase in community-associated non-invasive MSSA
      infections. When compared with MSSA infections, patients with non-multiresistant
      MRSA infections were more likely to be older, have hospital-onset infections and
      be Maori or Pacific Peoples. CONCLUSIONS: Our work provides valuable baseline
      data on the epidemiology and trends of S. aureus infections in New Zealand. The
      significant increase in community-associated S. aureus infections is of public
      health importance. Future studies should investigate the reasons underlying this
      concerning trend.

PMID- 24299300
TI  - Induced abortion and breast cancer.

PMID- 24299299
TI  - Asymmetric homoenolate additions to acyl phosphonates through rational design of
      a tailored N-heterocyclic carbene catalyst.
AB  - A highly selective NHC-catalyzed synthesis of gamma-butyrolactones from the
      fusion of enals and alpha-ketophosphonates has been developed. Computational
      modeling of competing transition states guided a rational design strategy to
      achieve enhanced levels of enantioselectivity with a new tailored C1-symmetric
      biaryl-saturated imidazolium-derived NHC catalyst. 

PMID- 24299301
TI  - OneBac: platform for scalable and high-titer production of adeno-associated virus
      serotype 1-12 vectors for gene therapy.
AB  - Scalable and genetically stable recombinant adeno-associated virus (rAAV)
      production systems combined with facile adaptability for an extended repertoire
      of AAV serotypes are required to keep pace with the rapidly increasing clinical
      demand. For scalable high-titer production of the full range of rAAV serotypes 1
      12, we developed OneBac, consisting of stable insect Sf9 cell lines harboring
      silent copies of AAV1-12 rep and cap genes induced upon infection with a single
      baculovirus that also carries the rAAV genome. rAAV burst sizes reach up to 5 *
      10(5) benzonase-resistant, highly infectious genomic particles per cell,
      exceeding typical yields of current rAAV production systems. In contrast to
      recombinant rep/cap baculovirus strains currently employed for large-scale rAAV
      production, the Sf9rep/cap cell lines are genetically stable, leading to
      undiminished rAAV burst sizes over serial passages. Thus, OneBac combines full
      AAV serotype options with the capacity for stable scale-up production, the
      current bottleneck for the transition of AAV from gene therapy trials to routine
      clinical treatment.

PMID- 24299302
TI  - Accuracy and robustness of dynamical tracking of average glycemia (A1c) to
      provide real-time estimation of hemoglobin A1c using routine self-monitored blood
      glucose data.
AB  - BACKGROUND: Laboratory hemoglobin A1c (HbA1c) assays are typically done only
      every few months. However, self-monitored blood glucose (SMBG) readings offer the
      possibility for real-time estimation of HbA1c. We present a new dynamical method
      tracking changes in average glycemia to provide real-time estimation of A1c
      (eA1c). MATERIALS AND METHODS: A new two-step algorithm was constructed that
      includes: (1) tracking fasting glycemia to compute base eA1c updated with every
      fasting SMBG data point and (2) calibration of the base eA1c trace with monthly
      seven-point SMBG profiles to capture the principal components of blood glucose
      variability and produce eA1c. A training data set (n=379 subjects) was used to
      estimate model parameters. The model was then fixed and applied to an independent
      test data set (n=375 subjects). Accuracy was evaluated in the test data set by
      computing mean absolute deviation (MAD) and mean absolute relative deviation
      (MARD) of eA1c from reference HbA1c, as well as eA1c-HbA1c correlation. RESULTS:
      MAD was 0.50, MARD was 6.7%, and correlation between eA1c and reference HbA1c was
      r=0.76. Using an HbA1c error grid plot, 77.5% of all eA1c fell within 10% from
      reference HbA1c, and 97.9% fell within 20% from reference. CONCLUSIONS: A
      dynamical estimation model was developed that achieved accurate tracking of
      average glycemia over time. The model is capable of working with infrequent SMBG
      data typical for type 2 diabetes, thereby providing a new tool for HbA1c
      estimation at the patient level. The computational demands of the procedure are
      low; thus it is readily implementable into home SMBG meters. Real-time HbA1c
      estimation could increase patients' motivation to improve diabetes control.

PMID- 24299303
TI  - Unstimulated leukapheresis in patients and donors: comparison of two apheresis
      systems.
AB  - BACKGROUND: Unstimulated mononuclear cell (MNC) apheresis plays a role in the
      generation of donor lymphocytes (DLIs; healthy donors) and in extracorporeal
      photopheresis (ECP; patients). The new apheresis system Spectra Optia MNC has
      been shown in small studies to be capable of performing the desired cell
      collections, but larger data sets from real-life clinical apheresis procedures
      are lacking. STUDY DESIGN AND METHODS: Presented are comparative data from DLI
      collections randomly performed with either the new technology or a clinical
      standard technology, COBE Spectra MNC, as well as data from patients with chronic
      graft-versus-host disease undergoing MNC collections alternating between the two
      apheresis systems to generate products for ECP. Target cell yield and collection
      efficiency, product volume, nontarget cell contamination, platelet (PLT)
      attrition, and some process variables such as process volume and time were
      analyzed. RESULTS: For most relevant apheresis outcomes, differences between the
      devices were at best marginal. Spectra Optia MNC collections in patients, but not
      in donors, took 10% longer to achieve the target process volume. Not
      unexpectedly, given previous observations for granulocyte-colony-stimulating
      factor-stimulated leukapheresis, the novel device collected smaller products with
      less red blood cell contamination. PLT attrition with Spectra Optia MNC was
      markedly lower in donors. ECP apheresis outcome variability was, to a significant
      degree, donor dependent, irrespective of the device used. CONCLUSION: Based on
      more than 200 unstimulated apheresis procedures, we conclude that both apheresis
      systems are safe, robust, and equally suitable for unstimulated MNC collections.
      Both can be successfully run with manufacturer-recommended settings and
      algorithms.

PMID- 24299305
TI  - Fluorescent aptasensor based on aggregation-induced emission probe and graphene
      oxide.
AB  - Recently, a great variety of aggregation-induced emission (AIE)-active molecules
      has been utilized to design bioprobes for label-free fluorescent turn-on
      aptasensing with high sensitivity. However, due to nonspecific binding
      interaction between aptamer and AIE probe, these AIE-based aptasensors have
      nearly no selectivity, thereby significantly limiting the development. In this
      work, a 9,10-distyrylanthracene with two ammonium groups (DSAI) is synthesized as
      a novel AIE probe, and the fluorescent aptasensor based on DSAI and graphene
      oxide (GO) is developed for selective and sensitive sensing of targeted DNA and
      thrombin protein. Given its AIE property and high selectivity and sensitivity,
      this aptasensor can be also exploited to detect other targets. 

PMID- 24299306
TI  - Graphite oxide/metal-organic framework (MIL-101): remarkable performance in the
      adsorptive denitrogenation of model fuels.
AB  - A highly porous metal-organic framework (MOF), MIL-101 (Cr-benzenedicarboxylate),
      was synthesized in the presence of graphite oxide (GO) to produce GO/MIL-101
      composites. The porosity of the composites increased remarkably in the presence
      of a small amount of GO (<0.5% of MIL-101); however, further increases in GO
      reduced the porosity. GO also accelerated the synthesis of the MIL-101. The
      composites (GO/MIL-101) were used, for the first time, in liquid-phase
      adsorptions. The adsorptive removal of nitrogen-containing compounds (NCCs) and
      sulfur-containing compounds (SCCs) from model fuels demonstrated the potential
      applications of the composites in adsorptions, and the adsorption capacity was
      dependent on the surface area and pore volume of the composites. Most
      importantly, the GO/MIL-101 composite has the highest adsorption capacity for
      NCCs among reported adsorbents so far, partly because of the increased porosity
      of the composite. Finally, the results suggest that GO could be used in the
      synthesis of highly porous MOF composites, and the obtained materials could be
      used in various adsorptions in both liquid and gas/vapor phase (such as H2, CH4,
      and CO2 storage) adsorptions, because of the high porosity and functional GO. 

PMID- 24299307
TI  - Monitoring of minimal residual disease in acute leukemia by multiparametric flow
      cytometry.
AB  - In this review, we discuss methodological principles and clinical applications of
      minimal residual disease (MRD) assays based on multiparameter flow cytometry
      (MFC). The introduction of methods for MRD detection has revolutionized
      monitoring of treatment response in acute leukemia. Great progress has been made
      in the development of wide array of flow cytometric techniques for rare event
      detection. This advance was accompanied by increasingly greater understanding of
      the immunophenotypic features of leukemic and normal lymphoid cells, and of the
      antigenic differences that make MRD studies possible. Immunologic testing of MRD
      relies on "leukemia-associated" immunophenotypes which can be identified by MFC
      in the most of acute leukemia cases. The recent technical innovations in routine
      MFC (3 lasers and>=8 colors) and the new developments in software for data
      analysis make this technology the most attractive for MRD diagnostics. The
      importance of MFC methodology will be further strengthened by the ongoing
      international standardization efforts. Results of MRD testing provide unique and
      clinically important information. The systematic application of immunologic
      techniques to study MRD in clinical samples has demonstrated the prognostic
      significance of MRD in patients, leading to the use of MRD to regulate treatment
      intensity in many contemporary protocols. The identification of new markers of
      MRD should increase the sensitivity of MRD testing by MFC and is required to
      widen the applicability of MRD studies.

PMID- 24299308
TI  - Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis.
AB  - Though the overall incidence of gastric cancer was decreasing in the developed
      countries in the past decades, it is still a serious threat to human health
      throughout the world. The molecular mechanisms underlying development of gastric
      cancer remains unclear. Though accumulating evidences shed a light on the
      implications of mitochondrial tumor suppressor (MTUS1) in carcinogenesis, the
      functional role of MTUS1 in regulation of proliferation and metastasis of gastric
      cancer cell is still poorly understood. In this study, we showed that the level
      of MTUS1 expression is relatively low in gastric cancer cell lines compared to
      normal gastric epithelial cells. By using clinical samples, we found that MTUS1
      expression is downregulated in tumor tissues compared to non-cancerous
      counterpart, and loss of MTUS1 was associated with high incidence of lymph node
      metastasis and poor patient outcome. Moreover, we demonstrate that MTUS1 has a
      significant impact on both the proliferative and metastatic potential of gastric
      cancer cell line, which were further supported by using mice tumor xenograft
      models. The present data suggested MTUS1 as a potential tumor suppressor in
      gastric cancer and might lead to a better understanding of gastric
      carcinogenesis.

PMID- 24299309
TI  - Inhibition of MEK sensitizes gastric cancer cells to TRAIL-induced apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has long
      been believed to be highly selective in inducing apoptosis in cancer cells, has
      turned out to be a molecule that induces a far more diverse range of effects. The
      aim of this study was to investigate whether or not ERK1/2 pathway is involved in
      antitumor effects of TRAIL on gastric cancer cells. In addition to activate the
      extrinsic and intrinsic apoptotic pathway, TRAIL also triggered the activation of
      ERK1/2. Inhibition of ERK1/2 signaling by MEK inhibitor U0126 promoted cell death
      via increased activation of caspases, drop in mitochondrial membrane potential
      and downregulation of XIAP, cIAP2 and Mcl-1. These results indicate that TRAIL
      induced rapid activation of ERK1/2 may be a survival mechanism to struggle
      against TRAIL assault at the early stage, and inhibition of ERK1/2 signaling can
      sensitize gastric cancer cells to TRAIL-induced apoptosis.

PMID- 24299310
TI  - Reduced STMN1 expression induced by RNA interference inhibits the bioactivity of
      pancreatic cancer cell line Panc-1.
AB  - Increased expression of STMN1 has been observed in many tumor forms, but its
      expression and potential biological role in pancreatic cancer is still unknown.
      In this study, we demonstrated that STMN1 was expressed to a large extent in
      pancreatic cancer tissues and cell lines as compared to normal pancreatic
      tissues. Suppression of STMN1 expression via transfection with STMN1-specific
      siRNA could not only significantly inhibit the proliferation, migration and
      invasion ability of Panc-1 cells, but also enhance the apoptosis of Panc-1 cells.
      In addition, downregulation of STMN1 obviously enhanced the acetylation level of
      alpha-tubulin. All these results indicated that STMN1 plays an important role in
      pancreatic cancer development, and might serve as a potential therapeutic target
      for pancreatic cancer.

PMID- 24299311
TI  - CD133 positive cells isolated from A549 cell line exhibited high liver metastatic
      potential.
AB  - Lung cancer remains a major cause of cancer-related lethality because of high
      incidence and recurrence in spite of significant advances in staging and therapy.
      In present study, we identified a subpopulation of cells isolated from the A549
      cell line with marker CD133. In vivo results showed that A549 CD133+ cells
      displayed high liver metastatic potential. Severe liver cell damage with tumor
      cell invasion revealed by pathological examination and these changes were
      consistent with the results of serological tests where the plasma GPT and GOT
      level are significantly higher than that of the control group. Compared with A549
      cells, A549 CD133+ cells expressed high levels of VEGF and exhibited high
      migration and invasion capability. In conclusion, we first reported that A549
      CD133+ cells exhibited characteristic of high liver metastatic potential which
      makes it be a suitable model for further study of liver metastasis of lung
      adenocarcinoma and provide a potential platform for anti-metastatic drug
      discovery or evaluation.

PMID- 24299312
TI  - The role Hiwi gene in the maintenance of lung cancer stem cell populations.
AB  - The Piwi family genes are highly conserved during evolution and play essential
      roles in stem cell self-renewal in diverse organisms. However, data on the
      function of Hiwi gene (a human homologue of Piwi family) in cancer stem cells
      remains obscure. The aim of this study was to investigate the role of Hiwi gene
      in the lung cancer stem cells. A rare population of SSCloAldebr cells had been
      identified as the lung cancer stem cells in our previous study. Compared with the
      human lung adenocarcinoma SPC-A1 cells, Hiwi gene was found to be highly
      expressed in the lung cancer stem cell population SSCloAldebr cells. After Hiwi
      gene knockdown in SSCloAldebr cells using a short hairpin RNA (shRNA) targeting
      Hiwi, the sphere formation ability and colony forming capacity of SSCloAldebr
      cells were remarkably impaired. Moreover, the in vivo studies showed that Hiwi
      knockdown suppressed the tumor growth of SSCloAldebr cells in nude mice. These
      findings suggest that Hiwi gene plays an important role in maintaining the stem
      cell properties of the lung cancer stem cells and may be a potential target for
      lung cancer therapy. Keywords: Hiwi gene, RNA interference, shRNA, lung cancer
      stem cell.

PMID- 24299313
TI  - Molecular alterations of the WWOX gene in nasopharyngeal carcinoma.
AB  - The WW domain-containing oxidoreductase (WWOX) gene is a candidate tumor
      suppressor gene. However, its exact mechanism is unclear. This study aimed to
      investigate the role of the WWOX gene in the development of nasopharyngeal
      carcinoma (NPC). Tissues were collected from 65 NPC patients. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis and
      immunohistochemistry were performed on NPC tissues to determine the expression of
      WWOX in NPC. The status of WWOX promoter methylation was analyzed by methylation
      specific PCR. Moreover, a PCR-based loss of heterozygosity (LOH) assay was
      conducted to detect the presence of WWOX deletion in NPC. The expression of WWOX
      in NPC tissues was significantly downregulated compared with that in non-tumorous
      tissues (P<0.05). The low expression of WWOX was significantly correlated with
      clinical TNM stage (P<0.05). In addition, methylation of WWOX was detected in 27
      (87%) of 31 WWOX protein negative tissues, suggesting that methylation of the
      WWOX promoter may regulate its expression. We found that a relatively high
      percentage of LOH was observed in NPC tissues. A significant inverse correlation
      between WWOX expression and methylation of its promoter was found in NPC tissue
      (rs=-0.582, P=0.001). However, LOH was not correlated with WWOX expression and
      methylation of its promoter. Our results show that WWOX gene alteration is an
      early genetic alteration and may contribute to tumorigenesis of NPC. WWOX may be
      an important prognostic marker in NPC.

PMID- 24299314
TI  - Autophagy inhibition enhances pan-Bcl-2 inhibitor AT-101-induced apoptosis in non
      small cell lung cancer.
AB  - Overexpression of anti-apoptotic Bcl-2 proteins is commonly observed in a variety
      of cancers and associated with resistance to conventional chemotherapeutic drugs.
      Targeting multiple anti-apoptotic proteins is now possible with the small
      molecule BH3 domain mimetics such as AT-101. Autophagy has been found to function
      as a resistance mechanism against apoptotic cell death. In this study, we
      investigated the role of autophagy in the AT-101-induced apoptotic death of human
      lung cancer cells. It was found that AT-101 dose-dependently induced both
      apoptosis and autophagy in A549 lung cancer cells. And the apoptotic cell death
      induced by AT-101 was greatly enhanced after autophagy inhibition. Our findings
      demonstrated that AT-101-induced autophagy was cytoprotective rather than being
      part of cell death process in lung cancer cells. Inhibition of autophagy in
      combination with efforts to enhance apoptosis through targeting the Bcl-2 family
      of proteins may be a promising strategy to overcome drug resistance.

PMID- 24299315
TI  - Transcriptome profiling of malignant transformed rat hepatic stem-like cells by
      aflatoxin B1.
AB  - Exposure to aflatoxins is strongly associated with hepatocellular carcinoma
      (HCC). Hepatic progenitor cells have been suggested to participate in the
      development of HCC. To further explore the molecular basis of aflatoxin-induced
      carcinogenesis, we utilized transcriptome profiles to examine the global gene
      expression alterations of malignant transformed rat hepatic stem-like cells. WB
      F344 cells were treated with continuous exposure to AFB1 (0.03, 0.1 and 0.2MUM),
      and gained certain characteristics of transformed cells identified by soft agar
      assay. Microarray analyses of the transformed cells found that 785, 625, and 751
      differentially expressed genes were detected in each exposure group,
      respectively. Hierarchical Clustering revealed that the effect of 0.1 and 0.2MUM
      exposure on the cells was conformable. Importantly, Gene Ontology analysis showed
      that malignant transformation of the hepatic stem-like cells was closely
      correlated to biological process, related to cell motion, cell adhesion, immune
      response and signal transduction. Accordingly, biological pathways was focused
      mainly on focal adhesion, regulation of actin cytoskeleton, ECM-receptor
      interaction, MAPK, TGF-beta and chemokine signaling pathway. A few genes involved
      in these pathways exhibited a dose response, including Cav2, Itgb3, Ccl2, Cx3cl1,
      Pdgfrb and Tmsb4x. These findings would contribute to a growing knowledgebase on
      the mechanism of aflatoxin-induced hepatocarcinogenesis.

PMID- 24299316
TI  - Coexpression of IL-6 and TNF-alpha: prognostic significance on breast cancer
      outcome.
AB  - Presented study was conducted to investigate the prognostic significance of the
      coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in
      breast cancer, by correlating their presence with clinicopathological
      characteristics indicative of tumor progression and the overall survival of
      breast cancer patients. One hundred twelve consecutive patients with primary
      breast cancer were prospectively included and evaluated. Serum concentrations of
      IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA).
      Median split was used to subdivide patients with low or high IL-6 and TNF-a
      levels. A positive association between the expression of the two cytokines was
      found. The coexpression of high IL-6 and TNF-alpha was independently associated
      with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion
      (aOR, 14.1), increasing the prognostic significance of each cytokine separately;
      it also provided additional prognostic information regarding survival, defining a
      high-risk subgroup of patients with significantly shorter survival and higher
      risk of death compared to patients with both cytokines low (aHR, 4.45) and
      patients with only one cytokine high (aHR, 3.63). Our findings suggest that the
      coexpression of these two cytokines could be used clinically as a useful tumor
      marker for the extension and the outcome of the disease.

PMID- 24299317
TI  - Prognostic significance of TMPRSS4 in gastric cancer.
AB  - Transmembrane protease, serine 4 (TMPRSS4), is a novel type of II transmembrane
      serine protease that is highly expressed in multiple cancers. However the
      expression pattern and clinical significance of TMPRSS4 in gastric cancer (GC)
      remain unclear. We aimed to investigate the clinical and prognostic importance of
      TMPRSS4 in GC. We performed an analysis of TMPRSS4 expression in 200 consecutive
      GC patients by immunohistochemistry. Based on TMPRSS4 positivity, the GC tissues
      were divided into TMPRSS4-positive group and TMPRSS4-negative group. The
      relationships between TMPRSS4 expression and clinicopathological parameters or
      prognosis were explored.The positivity of TMPRSS4 expression was significantly
      higher in GC tissues than in adjacent normal tissues (44.5% versus 9.5%,
      P<0.001). TMPRSS4 positivity was significantly correlated with depth of invasion,
      lymph node metastasis, and vessel invasion (all p<0.01). Survival analysis
      indicated that the TMPRSS4-positive group showed poorer survival than the TMPRSS4
      negative group (p<0.01). In terms of clinical stages, significantly different
      TMPRSS4 positivity was found only in stages II and III. Multivariate analysis
      showed that TMPRSS4 expression was an independent prognostic factor (p=0.013).
      Our data suggest that TMPRSS4 positivity is associated with GC invasion and lymph
      node metastasis. We propose TMPRSS4 expression as an indicator of poor prognosis
      in GC patients.

PMID- 24299318
TI  - Value of alpha-fetoprotein and clinical characteristics in patients with liver
      neoplasm.
AB  - This article aimed to investigate the value of alpha-fetoprotein (AFP) for the
      diagnosis of hepatocellular carcinoma (HCC) and to evaluate the relationship
      between AFP and various clinical variables of HCC comprehensively. A
      retrospective study of postoperative patients diagnosed with liver neoplasm from
      two Chinese centers was enrolled in our study.A total of 3050 patients were
      included. The best cut-off point of AFP for the diagnosis of HCC was 20ng/ml with
      ideal sensitivity (69.74%), specificity (91.18%), LR (4.12) and YI (0.61). Non
      HBV infection patients showed the highest specificity (94.44%) but lowest
      sensitivity (60.13%). In HBV infection. Patients, HBsAg, HBeAb, and HBcAb
      positive patients had the highest sensitivity (79.55%) and specificity (58.49%).
      AFP levels increased significantly in symptomatic patients (p=0.011). Those
      patients with tumor sizes >=10cm had much higher serum AFP level compared with
      smaller tumors ones (p=0.014). AFP levels increased remarkably in patients with
      vascular invasion (p=0.015). Stepwise logistic regression showed tumor size
      (>=10cm) was an independent predictor of elevated AFP (OR=2.743, 95%CI: 1.167
      6.447, P=0.021). The best discriminating AFP value for the diagnosis of HCC is
      20ng/ml; HBsAg, HBeAb and HBcAb positive patients have the optimal sensitivity
      and specificity; tumor size >= 10cm is an independent predictor of elevated AFP.

PMID- 24299319
TI  - Efficacy of a pegaspargase-based regimen in the treatment of newly-diagnosed
      extranodal natural killer/T-cell lymphoma.
AB  - Extranodal natural killer (NK)/T-cell lymphoma (ENKL) is an aggressive neoplasm
      with poor prognosis. Currently, there is no consensus on the optimal treatment of
      this disease. In this study, we report the efficacy of a pegaspargase (PEG-Asp)
      based chemotherapy, a DDGP regimen (PEG-Asp, dexamethasone, cisplatin,
      gemcitabine), for the treatment of newly-diagnosed ENKL. From August 2010 to May
      2012, 12 patients with newly-diagnosed stage II - IV ENKL were initially treated
      with a DDGP regimen in our center. Ten patients (10/12, 83.3%) achieved complete
      response (CR) and two (2/12, 16.7%) achieved partial response (PR). The objective
      overall response rate (ORR) was 100%. Three patients (3/12, 25.0%) relapsed, and
      as a result, two died of disease. Eight patients (8/12, 66.7%) were alive with no
      evidence of disease (NOD) after a median follow-up of 19 months (range 16 - 31
      months). Hematologic toxicity was the most frequent toxicity reported in this
      study. Grade 3/4 leukopenia and neutropenia were common and both occurred in
      eight patients (8/12, 66.7%), respectively. Additionally, six patients (6/12,
      50.0%) experienced grade 3/4 thrombocytopenia and three (3/12, 25.0%) experienced
      grade 3/4 anemia. However, no patient died of hematologic toxicity. Our results
      demonstrate the significant efficacy and safety profile of a DDGP regimen in the
      treatment of newly-diagnosed ENKL, and indicate the potential of this regimen as
      a first-line therapy against this disease.

PMID- 24299320
TI  - Individual-level data on the relationships of progression-free survival, post
      progression survival, and tumor response with overall survival in patients with
      advanced non-squamous non-small cell lung cancer.
AB  - The effects of first-line chemotherapy on overall survival (OS) might be
      confounded by subsequent therapies in patients with non-small cell lung cancer
      (NSCLC). We examined whether progression-free survival (PFS), post-progression
      survival (PPS), or tumor response could be valid surrogate endpoints for OS after
      first-line chemotherapies in advanced NSCLC by using individual-level data, given
      the lack of research in this area. Between April 2009 and June 2011, 50 patients
      with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first
      line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor
      response with OS were analyzed at the individual level. Spearman rank correlation
      analysis and linear regression analysis showed that PPS was strongly correlated
      with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r
      = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS
      (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second
      line treatment, the best response to second-line treatment, and number of
      regimens used after progression following first-line chemotherapy were
      significantly associated with PPS (P < 0.05). Analysis of individual-level data
      suggested that PPS could be used as a surrogate for OS in patients with advanced
      non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited
      options for subsequent chemotherapy. Our findings also suggest that subsequent
      treatment after disease progression following first-line chemotherapy may greatly
      influence OS. These results should be validated in other larger populations.

PMID- 24299322
TI  - Review article: nucleos(t)ide analogues in patients with chronic hepatitis B
      virus infection and chronic kidney disease.
AB  - BACKGROUND: The treatment of chronic hepatitis B (CHB) in patients with chronic
      kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir)
      or nucleotide (adefovir, tenofovir) analogues (NAs), but it may be complex and
      the information is scarce. Entecavir and tenofovir represent the currently
      recommended first-line NAs for NA-naive CHB patients, while tenofovir is the NA
      of choice for CHB patients with resistance to nucleosides. AIM: To review the
      efficacy and safety of NAs in adult CHB patients with CKD and to provide
      reasonable recommendations for their optimal management. METHODS: Literature
      search in PubMed/Medline and manual search of relevant articles, reviews and book
      chapters. RESULTS: NAs are cleared by kidneys and their dosage should be adjusted
      in patients with creatinine clearance <50 mL/min. There are concerns about
      nephrotoxic potential of the nucleotides, particularly adefovir, while
      improvements of creatinine clearance have been reported under telbivudine. Most
      existing data in CHB patients with CKD are for lamivudine and, less frequently,
      for other NAs, mostly entecavir. Besides CHB, NA should be used in case of
      immunosuppressive therapy in any HBsAg-positive patient with CKD including renal
      transplant (RT) recipients and in anti-HBs-positive recipients of kidney grafts
      from HBsAg-positive donors. CONCLUSIONS: Chronic hepatitis B patients with
      chronic kidney disease receiving nucleoside analogues should be followed
      carefully for treatment efficacy and renal safety. Despite the absence of strong
      data, entecavir and telbivudine seem to be the preferred options for nucleoside
      analogue-naive CHB patients with chronic kidney disease, depending on viraemia
      and severity of renal dysfunction. More studies are certainly needed in this
      setting.

PMID- 24299324
TI  - Commentary: broadening the focus of coeliac management to follow-up strategies.

PMID- 24299323
TI  - Randomised clinical trial: daily pantoprazole magnesium 40 mg vs. esomeprazole 40
      mg for gastro-oesophageal reflux disease, assessed by endoscopy and symptoms.
AB  - BACKGROUND: Pantoprazole magnesium (pantoprazole-Mg) may display extended
      inhibition of the proton pump with the potential for improved clinical efficacy
      in gastro-oesophageal reflux disease (GERD). AIM: To compare the efficacy of
      pantoprazole-Mg and esomeprazole in GERD. METHODS: Gastro-oesophageal reflux
      disease (Los Angeles grades A-D) patients were randomised to 4 weeks of treatment
      with pantoprazole-Mg (n = 290) or esomeprazole (n = 288), both 40 mg once daily,
      in this multicentre (14 Brazilian sites in 9 cities), double-blind study, with an
      additional 4 weeks' treatment in nonresponding patients. Severity of oesophagitis
      (at endoscopy) and GERD-related symptoms (ReQuest-GI) were assessed. The primary
      end point was the proportion of patients in complete remission (ReQuest-GI score
      <1.73 plus endoscopic healing) at week 4. RESULTS: Complete remission occurred in
      61% of patients in each treatment group at 4 weeks (primary endpoint) and in 81%
      and 79% of patients in the pantoprazole-Mg and esomeprazole groups at 8 weeks,
      with no significant differences. Mucosal healing rates were high and not
      significantly different. At 8 weeks, symptom relief with pantoprazole-Mg was
      significantly greater than that with esomeprazole (91.6% vs. 86.0%, P = 0.0370)
      because of continued improvement in symptoms with pantoprazole-Mg from week 4 to
      week 8 (P = 0.0206). CONCLUSIONS: Pantoprazole-Mg 40 mg was at least as effective
      as esomeprazole 40 mg for complete remission and the mucosal healing rate was
      high. Symptom relief with pantoprazole-Mg continued to improve from 4 to 8 weeks
      and was greater than that with esomeprazole at week 8, suggesting an extended
      period of treatment effect (ClinicalTrials.gov identifier: NCT01132638).

PMID- 24299325
TI  - Letter: acute severe ulcerative colitis - should all patients be treated equally?

PMID- 24299326
TI  - Letter: acute severe ulcerative colitis - should all patients be treated equally?
      Authors' reply.

PMID- 24299327
TI  - Letter: guidelines for the management of autoimmune hepatitis.

PMID- 24299328
TI  - Letter: guidelines for the management of autoimmune hepatitis - author's reply.

PMID- 24299329
TI  - Letter: flu-like illness with mercaptopurine and azathioprine in inflammatory
      bowel disease.

PMID- 24299330
TI  - Postglacial northward expansion and genetic differentiation between migratory and
      sedentary populations of the broad-tailed hummingbird (Selasphorus platycercus).
AB  - Unlike other migratory hummingbirds in North America, the broad-tailed
      hummingbird (Selasphorus platycercus) exhibits both long-distance migratory
      behaviour in the USA and sedentary behaviour in Mexico and Guatemala. We examined
      the evolution of migration linked to its northward expansion using a
      multiperspective approach. We analysed variation in morphology, mitochondrial and
      nuclear DNA, estimated migration rates between migratory and sedentary
      populations, compared divergence times with the occurrence of Quaternary climate
      events and constructed species distribution models to predict where migratory and
      sedentary populations resided during the Last Glacial Maximum (LGM) and Last
      Interglacial (LIG) events. Our results are consistent with a recent northward
      population expansion driven by migration from southern sedentary populations.
      Phylogeographical analyses and population genetics methods revealed that
      migratory populations in the USA and sedentary populations in Mexico of the
      platycercus subspecies form one admixed population, and that sedentary
      populations from southern Mexico and Guatemala (guatemalae) undertook independent
      evolutionary trajectories. Species distribution modelling revealed that the
      species is a niche tracker and that the climate conditions associated with modern
      obligate migrants in the USA were not present during the LIG, which provides
      indirect evidence for recent migratory behaviour in broad-tailed hummingbirds on
      the temporal scale of glacial cycles. The finding that platycercus hummingbirds
      form one genetic population and that suitable habitat for migratory populations
      was observed in eastern Mexico during the LIG also suggests that the conservation
      of overwintering sites is crucial for obligate migratory populations currently
      facing climate change effects.

PMID- 24299331
TI  - Plusoptix S08 sensitivity in detecting strabismus as amblyogenic risk factor.
AB  - PURPOSE: To evaluate the sensitivity of photoscreener Plusoptix S08 in screening
      strabismus. METHODS: Eighty-three consecutive patients were examined by a single
      expert to determine the type and amount of the deviation. Then photoscreening was
      done for all the patients via Plusoptix S08 photoscreener (Plusoptix GmbH,
      Nuremberg, Germany) on the same day, using the default software for referring the
      patients. RESULTS: The age range was between 6 months and 40 years. The overall
      sensitivity of the device to detect strabismus is 70%; it was 25% for exophoria,
      67% for esotropia, 73% for exotropia, and 89% in patients who had mixed
      strabismus. Regarding degree of deviation, sensitivity was 46% in deviations less
      than 30 prism diopters (PD) and rises while the degree of deviation increases.
      CONCLUSIONS: Our research shows that Plusoptix should not be used solely in
      evaluating strabismus because its sensitivity decreases significantly specially
      in esotropic patients with less than 30 PD deviations.

PMID- 24299332
TI  - Strabismus surgery outcomes after scleral buckling procedures for retinal
      reattachment.
AB  - OBJECTIVE: To investigate the outcomes of strabismus surgery in patients with a
      prior history of a scleral buckling procedure for retinal reattachment. METHODS:
      We reviewed the medical records of 18 patients who underwent strabismus surgery
      following a scleral buckling procedure and investigated the effect of multiple
      variables on postoperative alignment after strabismus surgery including gender,
      age, surgeon, number of strabismus surgeries, adjustable suture use, previous
      pars plana vitrectomy, preoperative best-corrected visual acuity, and scleral
      buckle removal. Outcomes were considered successful if there was <= 10 prism
      diopters (PD) residual horizontal and/or <= 4 PD residual vertical deviations.
      Statistical analyses were performed using Fisher's exact test, Mann-Whitney test,
      and nominal logistic regression. RESULTS: Success using our criteria of motor
      alignment was achieved in 6 of 18 eyes (33%). A higher rate of success was found
      in the scleral buckle removal group (success with buckle removal, 62.5%; success
      without buckle removal, 10.0%; p = 0.04). Nominal logistic regression analysis
      showed scleral buckle removal was the most significant factor associated with
      successful surgical alignment (p = 0.03; odds ratio = 16.67). Although the
      success rate was higher in the adjustable suture group (50% in adjustable group
      vs 14.3% in non-adjustable group: Fisher's exact test, p = 0.30), this difference
      was not statistically significant. No retinal redetachments occurred after
      scleral buckle removal. CONCLUSIONS: These results suggest that scleral buckles
      can be safely removed in selected patients with strabismus following retinal
      reattachment surgery and scleral buckle removal may improve ocular alignment
      following strabismus surgery.

PMID- 24299333
TI  - Haematological and molecular responses in refractory anaemia with ring
      sideroblasts and thrombocytosis treated with lenalidomide.

PMID- 24299334
TI  - Health status of independently living older adults in Romania.
AB  - AIM: Aging is affecting health care all over Europe, but it is expected to have a
      much greater impact in Eastern Europe. Reliable data on various indicators of
      health of older adults in Eastern Europe are lacking. The objectives of the
      present study were to describe the health of older Romanian adults, and to
      examine its relationship with sociodemographic, psychological and social factors.
      METHODS: This cross-sectional study used a stratified sample of 600 independent
      living older Romanian adults from the great metropolitan area of Bucharest; 549
      citizens aged >= 65 years participated. Data were collected by a mailed
      questionnaire and interviews. Measurements included self-rated health, the number
      of chronic conditions, the Short Form-20, the Eysenck Personality Questionnaire
      and Social support. RESULTS: Romanian older adults rate their health as "fair".
      On average, they report three chronic conditions. They more frequently have
      problems in executing daily activities as compared with older adults from other
      European countries. Three components of health are identified: independent
      functioning, suffering from chronic diseases and psychological health. Regression
      analysis shows that age, education and social support are related to each
      component, and neuroticism and extraversion to two components of health.
      CONCLUSIONS: A comparison with international data shows various indicators of
      health of older Romanian adults to be relatively worse. The three identified
      components of health offer opportunities for an integrated approach to deal with
      the health care needs of older citizens.

PMID- 24299336
TI  - Equipment and staffing are vital to 6Cs' success.

PMID- 24299335
TI  - Immune responses to intramuscular administration of alipogene tiparvovec (AAV1
      LPL(S447X)) in a phase II clinical trial of lipoprotein lipase deficiency gene
      therapy.
AB  - Cellular immune responses to adeno-associated viral (AAV) vectors used for gene
      therapy have been linked to attenuated transgene expression and loss of efficacy.
      The impact of such cellular immune responses on the clinical efficacy of
      alipogene tiparvovec (Glybera; AAV1-LPL(S447X); uniQure), a gene therapy
      consisting of intramuscular administration of a recombinant AAV1 mediating muscle
      directed expression of lipoprotein lipase (LPL), was investigated. Five subjects
      with LPL deficiency (LPLD) were administered intramuscularly with a dose of 1 *
      10(12) gc/kg alipogene tiparvovec. All subjects were treated with immune
      suppression starting shortly before administration of alipogene tiparvovec and
      maintained until 12 weeks after administration. Systemic antibody and T cell
      responses against AAV1 and LPL(S447X), as well as local cellular immune responses
      in the injected muscle, were investigated in five LPLD subjects. Long-term
      transgene expression was demonstrated despite a transient systemic cellular
      response and a stable humoral immune response against the AAV1 capsid protein.
      Cellular infiltrates were found in four of the five subjects but were not
      associated with adverse clinical events or elevation of inflammation markers.
      Consistent herewith, CD8+ T cells in the infiltrates lacked cytotoxic potential.
      Furthermore, FoxP3+/CD4+ T cells were found in the infiltrates, suggesting that
      multiple mechanisms contribute to local tolerance. Systemic and local immune
      responses induced by intramuscular injection of alipogene tiparvovec did not
      appear to have an impact on safety and did not prevent LPL transgene expression.
      These findings support the use of alipogene tiparvovec in individuals with LPLD
      and indicate that muscle-directed AAV-based gene therapy remains a promising
      approach for the treatment of human diseases.

PMID- 24299337
TI  - New recruitment campaign may encourage nurse leavers to return.

PMID- 24299342
TI  - CNO wants to 'shine a light' on the realities of everyday care.

PMID- 24299354
TI  - The named nurse concept: 'But we have been doing this for years'.

PMID- 24299360
TI  - Child obesity.

PMID- 24299361
TI  - Nursing a sense of family.
AB  - Rosemary Jenkinson was named nurse of the year in 1991 in recognition of her work
      to establish a community home for children with profound sensory disabilities.
      Winning the award was a confidence booster and a responsibility, she says.

PMID- 24299362
TI  - Match words with actions.
AB  - Promoted as fundamental to compassionate and effective health care, many trusts
      are using the 6Cs to reinforce work they had already started and to achieve
      further improvements. Some nurses remain uncertain about its implementation.

PMID- 24299363
TI  - How the 6Cs made us a stronger team.
AB  - Staff from the renal division at King's College Hospital NHS Foundation Trust
      (KCH) explain how they implemented the 6Cs and the difference these fundamental
      nursing values have made to staff and patients.

PMID- 24299378
TI  - Where are the unions when it comes to whistleblowing?

PMID- 24299379
TI  - A fresh approach is needed to help smokers who want to quit.

PMID- 24299380
TI  - Help inpatients by offering them nicotine replacement therapy.

PMID- 24299381
TI  - NHS chaplains are professional members of the healthcare team.

PMID- 24299382
TI  - Do not employ more admin staff at the expense of the front line.

PMID- 24299384
TI  - Zero-hours contracts lead to gross exploitation of workers.

PMID- 24299385
TI  - Genetics: examining your competency of practice on a regular basis.
AB  - This is the seventh article in a series examining how nurses can develop
      confidence and competence in genetics and genomics health care. This article
      focuses on identifying the nurse's awareness of genetic and genomic issues and
      the effect this has on his or her practice. It considers the importance of
      reflection in recognising these issues as well as areas where professional
      development in genetics and genomics may be beneficial. 

PMID- 24299386
TI  - Diagnosis and management of patients with Bell's palsy.
AB  - Bell's palsy (idiopathic facial paralysis) is the most common cause of acute
      unilateral facial nerve paralysis. Although it is usually a self-limiting
      condition, it can be distressing for the patient. Many people who experience one
      sided facial paralysis fear that it is a symptom of stroke. However, there are
      subtle differences between Bell's palsy and stroke. This article discusses
      potential causes of the condition and identifies the differences between Bell's
      palsy and stroke. In addition, appropriate strategies for the care of patients
      with the condition are suggested. Management includes antiviral medication,
      corticosteroid therapy, eye care, botulinum toxin type A injection,
      physiotherapy, surgery and acupuncture. Psychological and emotional care of these
      patients is also important because any facial disability caused by facial nerve
      paralysis can result in anxiety and stress. 

PMID- 24299387
TI  - Successful preceptorship of newly qualified nurses.
AB  - There is widespread recognition that many newly qualified nurses find it
      difficult to make the transition from completing their university course to
      taking up their first registered nurse post. Preceptorship programmes during the
      first year of registered nurse practice have been recommended by the Department
      of Health. Preceptors have an important role in ensuring successful transition of
      the newly qualified nurse; however they also require practical guidance on how
      best to support the nurse. This article identifies aspects that need to be
      considered when guiding a registered nurse colleague rather than a student.
      Preceptorship concerns four main areas: orientation to patients and services
      provided locally, real-time clinical reasoning, skill review and refinement, and
      socialisation within the healthcare team. The article will explore each of these
      areas. 

PMID- 24299388
TI  - Atrial fibrillation.

PMID- 24299389
TI  - Ready, steady, go for it.

PMID- 24299391
TI  - Providing an extra strand of support.

PMID- 24299393
TI  - Primary experience.

PMID- 24299394
TI  - Surface photochemistry of adsorbed nitrate: the role of adsorbed water in the
      formation of reduced nitrogen species on alpha-Fe2O3 particle surfaces.
AB  - The surface photochemistry of nitrate, formed from nitric acid adsorption, on
      hematite (alpha-Fe2O3) particle surfaces under different environmental conditions
      is investigated using X-ray photoelectron spectroscopy (XPS). Following exposure
      of alpha-Fe2O3 particle surfaces to gas-phase nitric acid, a peak in the N1s
      region is seen at 407.4 eV; this binding energy is indicative of adsorbed
      nitrate. Upon broadband irradiation with light (lambda > 300 nm), the nitrate
      peak decreases in intensity as a result of a decrease in adsorbed nitrate on the
      surface. Concomitant with this decrease in the nitrate coverage, there is the
      appearance of two lower binding energy peaks in the N1s region at 401.7 and 400.3
      eV, due to reduced nitrogen species. The formation as well as the stability of
      these reduced nitrogen species, identified as NO(-) and N(-), are further
      investigated as a function of water vapor pressure. Additionally, irradiation of
      adsorbed nitrate on alpha-Fe2O3 generates three nitrogen gas-phase products
      including NO2, NO, and N2O. As shown here, different environmental conditions of
      water vapor pressure and the presence of molecular oxygen greatly influence the
      relative photoproduct distribution from nitrate surface photochemistry. The
      atmospheric implications of these results are discussed. 

PMID- 24299395
TI  - Integrative testing of how environments from the past to the present shape
      genetic structure across landscapes.
AB  - Tests of the genetic structure of empirical populations typically focus on the
      correlative relationships between population connectivity and geographic and/or
      environmental factors in landscape genetics. However, such tests may overlook or
      misidentify the impact of candidate factors on genetic structure, especially when
      connectivity patterns differ between past and present populations because of
      shifting environmental conditions over time. Here we account for the underlying
      demographic component of population connectivity associated with a temporarily
      dynamic landscape in tests of the factors structuring population genetic
      variation in an Australian lizard, Lerista lineopunctulata, from 24 nuclear loci.
      Correlative tests did not support significant effect from factors associated with
      a static contemporary landscape. However, spatially explicit demographic modeling
      of genetic differentiation shows that changes in environmental conditions (as
      estimated from paleoclimatic data) and corresponding distributional shifts from
      the past to present landscape significantly structures genetic variation. Results
      from model-based inference (i.e., from an integrative modeling approach that
      generates spatially explicit expectations that are tested with approximate
      Bayesian computation) contrasts with those from correlative analyses,
      highlighting the importance of expanding the landscape genetic perspective to
      tests the links between pattern and process, revealing how factors shape patterns
      of genetic variation within species. 

PMID- 24299396
TI  - Examining the full effects of landscape heterogeneity on spatial genetic
      variation: a multiple matrix regression approach for quantifying geographic and
      ecological isolation.
AB  - Understanding the effects of landscape heterogeneity on spatial genetic variation
      is a primary goal of landscape genetics. Ecological and geographic variables can
      contribute to genetic structure through geographic isolation, in which geographic
      barriers and distances restrict gene flow, and ecological isolation, in which
      gene flow among populations inhabiting different environments is limited by
      selection against dispersers moving between them. Although methods have been
      developed to study geographic isolation in detail, ecological isolation has
      received much less attention, partly because disentangling the effects of these
      mechanisms is inherently difficult. Here, I describe a novel approach for
      quantifying the effects of geographic and ecological isolation using multiple
      matrix regression with randomization. I explored the parameter space over which
      this method is effective using a series of individual-based simulations and found
      that it accurately describes the effects of geographic and ecological isolation
      over a wide range of conditions. I also applied this method to a set of real
      world datasets to show that ecological isolation is an often overlooked but
      important contributor to patterns of spatial genetic variation and to demonstrate
      how this analysis can provide new insights into how landscapes contribute to the
      evolution of genetic variation in nature. 

PMID- 24299397
TI  - Perched at the mito-nuclear crossroads: divergent mitochondrial lineages
      correlate with environment in the face of ongoing nuclear gene flow in an
      Australian bird.
AB  - Relationships among multilocus genetic variation, geography, and environment can
      reveal how evolutionary processes affect genomes. We examined the evolution of an
      Australian bird, the eastern yellow robin Eopsaltria australis, using
      mitochondrial (mtDNA) and nuclear (nDNA) genetic markers, and bioclimatic
      variables. In southeastern Australia, two divergent mtDNA lineages occur east and
      west of the Great Dividing Range, perpendicular to latitudinal nDNA structure. We
      evaluated alternative scenarios to explain this striking discordance in landscape
      genetic patterning. Stochastic mtDNA lineage sorting can be rejected because the
      mtDNA lineages are essentially distinct geographically for > 1500 km. Vicariance
      is unlikely: the Great Dividing Range is neither a current barrier nor was it at
      the Last Glacial Maximum according to species distribution modeling; nuclear gene
      flow inferred from coalescent analysis affirms this. Female philopatry
      contradicts known female-biased dispersal. Contrasting mtDNA and nDNA
      demographies indicate their evolutionary histories are decoupled. Distance-based
      redundancy analysis, in which environmental temperatures explain mtDNA variance
      above that explained by geographic position and isolation-by-distance, favors a
      nonneutral explanation for mitochondrial phylogeographic patterning. Thus,
      observed mito-nuclear discordance accords with environmental selection on a
      female-linked trait, such as mtDNA, mtDNA-nDNA interactions or genes on W
      chromosome, driving mitochondrial divergence in the presence of nuclear gene
      flow. 

PMID- 24299399
TI  - Spatio-temporal changes in the structure of an Australian frog hybrid zone: a 40
      year perspective.
AB  - Spatio-temporal studies of hybrid zones provide an opportunity to test
      evolutionary hypotheses of hybrid zone maintenance and movement. We conducted a
      landscape genetics study on a classic hybrid zone of the south-eastern Australian
      frogs, Litoria ewingii and Litoria paraewingi. This hybrid zone has been
      comprehensively studied since the 1960s, providing the unique opportunity to
      directly assess changes in hybrid zone structure across time. We compared both
      mtDNA and male advertisement call data from two time periods (present and 1960s).
      Clinal analysis of the coincidence (same center) and concordance (same width) of
      these traits indicated that the center of the hybrid zone has shifted 1 km south
      over the last 40 years, although the width of the zone and the rate of
      introgression remained unchanged. The low frequency of hybrids, the strong
      concordance of clines within a time period, and the small but significant
      movement across the study period despite significant anthropogenic changes
      through the region, suggest the hybrid zone is a tension zone located within a
      low-density trough. Hybrid zone movement has not been considered common in the
      past but our findings highlight that it should be considered a crucial component
      to our understanding of evolution. 

PMID- 24299398
TI  - Evolutionary inferences from the analysis of exchangeability.
AB  - Evolutionary inferences are usually based on statistical models that compare mean
      genotypes or phenotypes (or their frequencies) among populations. An alternative
      is to use the full distribution of genotypes and phenotypes to infer the
      "exchangeability" of individuals among populations. We illustrate this approach
      by using discriminant functions on principal components to classify individuals
      among paired lake and stream populations of threespine stickleback in each of six
      independent watersheds. Classification based on neutral and nonneutral
      microsatellite markers was highest to the population of origin and next highest
      to populations in the same watershed. These patterns are consistent with the
      influence of historical contingency (separate colonization of each watershed) and
      subsequent gene flow (within but not between watersheds). In comparison to this
      low genetic exchangeability, ecological (diet) and morphological (trophic and
      armor traits) exchangeability was relatively high-particularly among populations
      from similar habitats. These patterns reflect the role of natural selection in
      driving parallel adaptive changes when independent populations colonize similar
      habitats. Importantly, however, substantial nonparallelism was also evident. Our
      results show that analyses based on exchangeability can confirm inferences based
      on statistical analyses of means or frequencies, while also refining insights
      into the drivers of-and constraints on-evolutionary diversification. 

PMID- 24299400
TI  - Integrating landscape genomics and spatially explicit approaches to detect loci
      under selection in clinal populations.
AB  - Uncovering the genetic basis of adaptation hinges on the ability to detect loci
      under selection. However, population genomics outlier approaches to detect
      selected loci may be inappropriate for clinal populations or those with unclear
      population structure because they require that individuals be clustered into
      populations. An alternate approach, landscape genomics, uses individual-based
      approaches to detect loci under selection and reveal potential environmental
      drivers of selection. We tested four landscape genomics methods on a simulated
      clinal population to determine their effectiveness at identifying a locus under
      varying selection strengths along an environmental gradient. We found all methods
      produced very low type I error rates across all selection strengths, but elevated
      type II error rates under "weak" selection. We then applied these methods to an
      AFLP genome scan of an alpine plant, Campanula barbata, and identified five
      highly supported candidate loci associated with precipitation variables. These
      loci also showed spatial autocorrelation and cline patterns indicative of
      selection along a precipitation gradient. Our results suggest that landscape
      genomics in combination with other spatial analyses provides a powerful approach
      for identifying loci potentially under selection and explaining spatially complex
      interactions between species and their environment. 

PMID- 24299401
TI  - Landscape genomics in Atlantic salmon (Salmo salar): searching for gene
      environment interactions driving local adaptation.
AB  - A growing number of studies are examining the factors driving historical and
      contemporary evolution in wild populations. By combining surveys of genomic
      variation with a comprehensive assessment of environmental parameters, such
      studies can increase our understanding of the genomic and geographical extent of
      local adaptation in wild populations. We used a large-scale landscape genomics
      approach to examine adaptive and neutral differentiation across 54 North American
      populations of Atlantic salmon representing seven previously defined genetically
      distinct regional groups. Over 5500 genome-wide single nucleotide polymorphisms
      were genotyped in 641 individuals and 28 bulk assays of 25 pooled individuals
      each. Genome scans, linkage map, and 49 environmental variables were combined to
      conduct an innovative landscape genomic analysis. Our results provide valuable
      insight into the links between environmental variation and both neutral and
      potentially adaptive genetic divergence. In particular, we identified markers
      potentially under divergent selection, as well as associated selective
      environmental factors and biological functions with the observed adaptive
      divergence. Multivariate landscape genetic analysis revealed strong associations
      of both genetic and environmental structures. We found an enrichment of growth
      related functions among outlier markers. Climate (temperature-precipitation) and
      geological characteristics were significantly associated with both potentially
      adaptive and neutral genetic divergence and should be considered as candidate
      loci involved in adaptation at the regional scale in Atlantic salmon. Hence, this
      study significantly contributes to the improvement of tools used in modern
      conservation and management schemes of Atlantic salmon wild populations. 

PMID- 24299402
TI  - Fine-scale genetic structure in a wild bird population: the role of limited
      dispersal and environmentally based selection as causal factors.
AB  - Individuals are typically not randomly distributed in space; consequently
      ecological and evolutionary theory depends heavily on understanding the spatial
      structure of populations. The central challenge of landscape genetics is
      therefore to link spatial heterogeneity of environments to population genetic
      structure. Here, we employ multivariate spatial analyses to identify
      environmentally induced genetic structures in a single breeding population of
      1174 great tits Parus major genotyped at 4701 single-nucleotide polymorphism
      (SNP) loci. Despite the small spatial scale of the study relative to natal
      dispersal, we found multiple axes of genetic structure. We built distance-based
      Moran's eigenvector maps to identify axes of pure spatial variation, which we
      used for spatial correction of regressions between SNPs and various external
      traits known to be related to fitness components (avian malaria infection risk,
      local density of conspecifics, oak tree density, and altitude). We found clear
      evidence of fine-scale genetic structure, with 21, seven, and nine significant
      SNPs, respectively, associated with infection risk by two species of avian
      malaria (Plasmodium circumflexum and P. relictum) and local conspecific density.
      Such fine-scale genetic structure relative to dispersal capabilities suggests
      ecological and evolutionary mechanisms maintain within-population genetic
      diversity in this population with the potential to drive microevolutionary
      change. 

PMID- 24299403
TI  - Why epistasis is important for selection and adaptation.
AB  - Organisms are built from thousands of genes that interact in complex ways. Still,
      the mathematical theory of evolution is dominated by a gene-by-gene perspective
      in which genes are assumed to have the same effects regardless of genetic
      background. Gene interaction, or epistasis, plays a role in some theoretical
      developments such as the evolution of recombination, reproductive isolation, and
      canalization, but is strikingly missing from our standard accounts of phenotypic
      adaptation. This absence is most puzzling within the field of quantitative
      genetics, which, despite its polygenic perspective and elaborate statistical
      representation of epistasis, has not found a single important role for gene
      interaction in evolution. To the contrary, there is a widespread consensus that
      epistasis is evolutionary inert, and that all we need to know to predict
      evolutionary dynamics is the additive component of the genetic variance. This
      view may have roots in convenience, but also in theoretical results showing that
      the response to selection derived from epistatic variance components is not
      permanent and will decay when selection is relaxed. I show that these results are
      tied to a conceptual confusion, and are misleading as general statements about
      the significance of epistasis for the selection response and adaptation. 

PMID- 24299404
TI  - Shifting fitness landscapes in response to altered environments.
AB  - The role of adaptation in molecular evolution has been contentious for decades.
      Here, we shed light on the adaptive potential in Saccharomyces cerevisiae by
      presenting systematic fitness measurements for all possible point mutations in a
      region of Hsp90 under four environmental conditions. Under elevated salinity, we
      observe numerous beneficial mutations with growth advantages up to 7% relative to
      the wild type. All of these beneficial mutations were observed to be associated
      with high costs of adaptation. We thus demonstrate that an essential protein can
      harbor adaptive potential upon an environmental challenge, and report a
      remarkable fit of the data to a version of Fisher's geometric model that focuses
      on the fitness trade-offs between mutations in different environments. 

PMID- 24299405
TI  - Cryptic choice of conspecific sperm controlled by the impact of ovarian fluid on
      sperm swimming behavior.
AB  - Despite evidence that variation in male-female reproductive compatibility exists
      in many fertilization systems, identifying mechanisms of cryptic female choice at
      the gamete level has been a challenge. Here, under risks of genetic
      incompatibility through hybridization, we show how salmon and trout eggs promote
      fertilization by conspecific sperm. Using in vitro fertilization experiments that
      replicate the gametic microenvironment, we find complete interfertility between
      both species. However, if either species' ova were presented with equivalent
      numbers of both sperm types, conspecific sperm gained fertilization precedence.
      Surprisingly, the species' identity of the eggs did not explain this cryptic
      female choice, which instead was primarily controlled by conspecific ovarian
      fluid, a semiviscous, protein-rich solution that bathes the eggs and is released
      at spawning. Video analyses revealed that ovarian fluid doubled sperm motile life
      span and straightened swimming trajectory, behaviors allowing chemoattraction up
      a concentration gradient. To confirm chemoattraction, cell migration tests
      through membranes containing pores that approximated to the egg micropyle showed
      that conspecific ovarian fluid attracted many more spermatozoa through the
      membrane, compared with heterospecific fluid or water. These combined findings
      together identify how cryptic female choice can evolve at the gamete level and
      promote reproductive isolation, mediated by a specific chemoattractive influence
      of ovarian fluid on sperm swimming behavior. 

PMID- 24299406
TI  - Constraints on the adult-offspring size relationship in protists.
AB  - The relationship between adult and offspring size is an important aspect of
      reproductive strategy. Although this filial relationship has been extensively
      examined in plants and animals, we currently lack comparable data for protists,
      whose strategies may differ due to the distinct ecological and physiological
      constraints on single-celled organisms. Here, we report measurements of adult and
      offspring sizes in 3888 species and subspecies of foraminifera, a class of large
      marine protists. Foraminifera exhibit a wide range of reproductive strategies;
      species of similar adult size may have offspring whose sizes vary 100-fold. Yet,
      a robust pattern emerges. The minimum (5th percentile), median, and maximum (95th
      percentile) offspring sizes exhibit a consistent pattern of increase with adult
      size independent of environmental change and taxonomic variation over the past
      400 million years. The consistency of this pattern may arise from evolutionary
      optimization of the offspring size-fecundity trade-off and/or from cell
      biological constraints that limit the range of reproductive strategies available
      to single-celled organisms. When compared with plants and animals, foraminifera
      extend the evidence that offspring size covaries with adult size across an
      additional five orders of magnitude in organism size. 

PMID- 24299407
TI  - Reed warbler hosts fine-tune their defenses to track three decades of cuckoo
      decline.
AB  - Interactions between avian hosts and brood parasites can provide a model for how
      animals adapt to a changing world. Reed warbler (Acrocephalus scirpaceus) hosts
      employ costly defenses to combat parasitism by common cuckoos (Cuculus canorus).
      During the past three decades cuckoos have declined markedly across England,
      reducing parasitism at our study site (Wicken Fen) from 24% of reed warbler nests
      in 1985 to 1% in 2012. Here we show with experiments that host mobbing and egg
      rejection defenses have tracked this decline in local parasitism risk: the
      proportion of reed warbler pairs mobbing adult cuckoos (assessed by responses to
      cuckoo mounts and models) has declined from 90% to 38%, and the proportion
      rejecting nonmimetic cuckoo eggs (assessed by responses to model eggs) has
      declined from 61% to 11%. This is despite no change in response to other nest
      enemies or mimetic model eggs. Individual variation in both defenses is predicted
      by parasitism risk during the host's egg-laying period. Furthermore, the response
      of our study population to temporal variation in parasitism risk can also explain
      spatial variation in egg rejection behavior in other populations across Europe.
      We suggest that spatial and temporal variation in parasitism risk has led to the
      evolution of plasticity in reed warbler defenses. 

PMID- 24299408
TI  - The challenge of species delimitation at the extremes: diversification without
      morphological change in philippine sun skinks.
AB  - An accurate understanding of species diversity is essential to studies across a
      wide range of biological subdisciplines. However, delimiting species remains
      challenging in evolutionary radiations where morphological diversification is
      rapid and accompanied by little genetic differentiation or when genetic lineage
      divergence is not accompanied by morphological change. We investigate the utility
      of a variety of recently developed approaches to examine genetic and
      morphological diversity, and delimit species in a morphologically conserved group
      of Southeast Asian lizards. We find that species diversity is vastly
      underestimated in this unique evolutionary radiation, and find an extreme case
      where extensive genetic divergence among lineages has been accompanied by little
      to no differentiation in external morphology. Although we note that different
      conclusions can be drawn when species are delimited using molecular
      phylogenetics, coalescent-based methods, or morphological data, it is clear that
      the use of a pluralistic approach leads to a more comprehensive appraisal of
      biodiversity, and greater appreciation for processes of diversification in this
      biologically important geographic region. Similarly, our approach demonstrates
      how recently developed methodologies can be used to obtain robust estimates of
      species limits in "nonadaptive" or "cryptic" evolutionary radiations. 

PMID- 24299409
TI  - Variation in thermal performance and reaction norms among populations of
      Drosophila melanogaster.
AB  - The major goal of evolutionary thermal biology is to understand how variation in
      temperature shapes phenotypic evolution. Comparing thermal reaction norms among
      populations from different thermal environments allows us to gain insights into
      the evolutionary mechanisms underlying thermal adaptation. Here, we have examined
      thermal adaptation in six wild populations of the fruit fly (Drosophila
      melanogaster) from markedly different natural environments by analyzing thermal
      reaction norms for fecundity, thorax length, wing area, and ovariole number under
      ecologically realistic fluctuating temperature regimes in the laboratory.
      Contrary to expectation, we found only minor differences in the thermal optima
      for fecundity among populations. Differentiation among populations was mainly due
      to differences in absolute (and partly also relative) thermal fecundity
      performance. Despite significant variation among populations in the absolute
      values of morphological traits, we observed only minor differentiation in their
      reaction norms. Overall, the thermal reaction norms for all traits examined were
      remarkably similar among different populations. Our results therefore suggest
      that thermal adaptation in D. melanogaster predominantly involves evolutionary
      changes in absolute trait values rather than in aspects of thermal reaction
      norms. 

PMID- 24299410
TI  - Sexual imprinting: what strategies should we expect to see in nature?
AB  - Sexual imprinting occurs when juveniles learn mate preferences by observing the
      phenotypes of other members of their populations, and it is ubiquitous in nature.
      Imprinting strategies, that is which individuals and phenotypes are observed and
      how strong preferences become, vary among species. Imprinting can affect trait
      evolution and the probability of speciation, and different imprinting strategies
      are expected to have different effects. However, little is known about how and
      why different imprinting strategies evolve, or which strategies we should expect
      to see in nature. We used a mathematical model to study how the evolution of
      sexual imprinting depends on (1) imprinting costs and (2) the sex-specific
      fitness effects of the phenotype on which individuals imprint. We found that even
      small fixed costs prevent the evolution of sexual imprinting, but small relative
      costs do not. When imprinting does evolve, we identified the conditions under
      which females should evolve to imprint on their fathers, their mothers, or on
      other members of their populations. Our results provide testable hypotheses for
      empirical work and help to explain the conditions under which sexual imprinting
      might evolve to promote speciation. 

PMID- 24299411
TI  - Neurospora and the dead-end hypothesis: genomic consequences of selfing in the
      model genus.
AB  - It is becoming increasingly evident that adoption of different reproductive
      strategies, such as sexual selfing and asexuality, greatly impacts genome
      evolution. In this study, we test theoretical predictions on genomic
      maladaptation of selfing lineages using empirical data from the model fungus
      Neurospora. We sequenced the genomes of four species representing distinct
      transitions to selfing within the history of the genus, as well as the
      transcriptome of one of these, and compared with available data from three
      outcrossing species. Our results provide evidence for a relaxation of purifying
      selection in protein-coding genes and for a reduced efficiency of transposable
      element silencing by Repeat Induced Point mutation. A reduction in adaptive
      evolution was also identified in the form of reduced codon usage bias in highly
      expressed genes of selfing Neurospora, but this result may be confounded by
      mutational bias. Potentially counteracting these negative effects, the nucleotide
      substitution rate and the spread of transposons is reduced in selfing species. We
      suggest that differences in substitution rate relate to the absence, in selfing
      Neurospora, of the asexual pathway producing conidia. Our results support the
      dead-end theory and show that Neurospora genomes bear signatures of both sexual
      and asexual reproductive mode. 

PMID- 24299412
TI  - Quantifying variation in speciation and extinction rates with clade data.
AB  - High-level phylogenies are very common in evolutionary analyses, although they
      are often treated as incomplete data. Here, we provide statistical tools to
      analyze what we name "clade data," which are the ages of clades together with
      their numbers of species. We develop a general approach for the statistical
      modeling of variation in speciation and extinction rates, including temporal
      variation, unknown variation, and linear and nonlinear modeling. We show how this
      approach can be generalized to a wide range of situations, including testing the
      effects of life-history traits and environmental variables on diversification
      rates. We report the results of an extensive simulation study to assess the
      performance of some statistical tests presented here as well as of the estimators
      of speciation and extinction rates. These latter results suggest the possibility
      to estimate correctly extinction rate in the absence of fossils. An example with
      data on fish is presented. 

PMID- 24299413
TI  - Evaluating a simple approximation to modeling the joint evolution of self
      fertilization and inbreeding depression.
AB  - A comprehensive understanding of plant mating system evolution requires detailed
      genetic models for both the mating system and inbreeding depression, which are
      often intractable. A simple approximation assuming that the mating system evolves
      by small infrequent mutational steps has been proposed. We examine its accuracy
      by comparing the evolutionarily stable selfing rates it predicts to those
      obtained from an explicit genetic model of the selfing rate, when inbreeding
      depression is caused by partly recessive deleterious mutations at many loci. Both
      models also include pollen limitation and pollen discounting. The approximation
      produces reasonably accurate predictions with a low or moderate genomic mutation
      rate to deleterious alleles, on the order of U = 0.02-0.2. However, for high
      mutation rates, the predictions of the full genetic model differ substantially
      from those of the approximation, especially with nearly recessive lethal alleles.
      This occurs because when a modifier allele affecting the selfing rate is rare,
      homozygous modifiers are produced mainly by selfing, which enhances the
      opportunity for purging nearly recessive lethals and increases the marginal
      fitness of the allele modifying the selfing rate. Our results confirm that
      explicit genetic models of selfing rate and inbreeding depression are required to
      understand mating system evolution. 

PMID- 24299414
TI  - Evolutionary constraints and the maintenance of individual specialization
      throughout succession.
AB  - Constraints on life-history traits, with their close links to fitness, are widely
      invoked as limits to niche expansion at most organizational levels.
      Theoretically, such constraints can maintain individual specialization by
      preventing adaptation to all niches available, but empirical evidence of them
      remains elusive for natural populations. This problem may be compounded by a
      tendency to seek constraints involving multiple traits, neglecting their added
      potential to manifest in trait expression across environments (i.e., within
      reaction norms). By replicating genotypes of a colonial marine invertebrate
      across successional stages in its local community, and taking a holistic approach
      to the analysis of ensuing reaction norms for fitness, we show the potential for
      individual specialization to be maintained by genetic constraints associated with
      these norms, which limit the potential for fitness at one successional stage to
      improve without loss of fitness at others. Our study provides new insight into
      the evolutionary maintenance of individual specialization in natural populations
      and reinforces the importance of reaction norms for studying this phenomenon. 

PMID- 24299415
TI  - Constraints on Mammalian forelimb development: insights from developmental
      disparity.
AB  - Tetrapod limb development has been studied extensively for decades, yet the
      strength and role of developmental constraints in this process remains
      unresolved. Mammals exhibit a particularly wide array of limb morphologies
      associated with various locomotion modes and behaviors, providing a useful system
      for identifying periods of developmental constraint and conserved developmental
      mechanisms or morphologies. In this study, landmark-based geometric morphometrics
      are used to investigate levels and patterns of morphological diversity
      (disparity) among the developing forelimbs of four mammals with diverse limb
      morphologies: mice, opossums, horses, and pigs. Results indicate that disparity
      among the forelimbs of these species slightly decreases or stays the same from
      the appearance of the limb ridge to the bud stage, and increases dramatically
      from the paddle through tissue regression stages. Heterochrony exhibited by the
      precocial opossum limb was not found to drive these patterns of morphological
      disparity, suggesting that the low disparity of the middle stages of limb
      development (e.g., paddle stage) is driven by processes operating within the limb
      and is likely not a result of embryo-wide constraint. 

PMID- 24299416
TI  - Differential introgression in a mosaic hybrid zone reveals candidate barrier
      genes.
AB  - Hybrid zones act as genomic sieves. Although globally advantageous alleles will
      spread throughout the zone and neutral alleles can be freely exchanged between
      species, introgression will be restricted for genes that contribute to
      reproductive barriers or local adaptation. Seminal fluid proteins (SFPs) are
      known to contribute to reproductive barriers in insects and have been proposed as
      candidate barrier genes in the hybridizing field crickets Gryllus pennsylvanicus
      and Gryllus firmus. Here, we have used 125 single nucleotide polymorphisms to
      characterize patterns of differential introgression and to identify genes that
      may contribute to prezygotic barriers between these species. Using a
      transcriptome scan of the male cricket accessory gland (the site of SFP
      synthesis), we identified genes with major allele frequency differences between
      the species. We then compared patterns of introgression for genes encoding SFPs
      with patterns for genes expressed in the same tissue that do not encode SFPs. We
      find no evidence that SFPs have reduced gene exchange across the cricket hybrid
      zone. However, a number of genes exhibit dramatically reduced introgression, and
      many of these genes encode proteins with functional roles consistent with known
      barriers. 

PMID- 24299417
TI  - The variability is in the sex chromosomes.
AB  - Sex differences in the mean trait expression are well documented, not only for
      traits that are directly associated with reproduction. Less is known about how
      the variability of traits differs between males and females. In species with sex
      chromosomes and dosage compensation, the heterogametic sex is expected to show
      larger trait variability ("sex-chromosome hypothesis"), yet this central
      prediction, based on fundamental genetic principles, has never been evaluated in
      detail. Here we show that in species with heterogametic males, male variability
      in body size is significantly larger than in females, whereas the opposite can be
      shown for species with heterogametic females. These results support the
      prediction of the sex-chromosome hypothesis that individuals of the heterogametic
      sex should be more variable. We argue that the pattern demonstrated here for sex
      specific body size variability is likely to apply to any trait and needs to be
      considered when testing predictions about sex-specific variability and sexual
      selection. 

PMID- 24299418
TI  - Evolution of sex determination systems with heterogametic males and females in
      silene.
AB  - The plant genus Silene has become a model for evolutionary studies of sex
      chromosomes and sex-determining mechanisms. A recent study performed in Silene
      colpophylla showed that dioecy and the sex chromosomes in this species evolved
      independently from those in Silene latifolia, the most widely studied dioecious
      Silene species. The results of this study show that the sex-determining system in
      Silene otites, a species related to S. colpophylla, is based on female
      heterogamety, a sex determination system that is unique among the Silene species
      studied to date. Our phylogenetic data support the placing of S. otites and S.
      colpophylla in the subsection Otites and the analysis of ancestral states
      suggests that the most recent common ancestor of S. otites and S. colpophylla was
      most probably dioecious. These observations imply that a switch from XX/XY sex
      determination to a ZZ/ZW system (or vice versa) occurred in the subsection
      Otites. This is the first report of two different types of heterogamety within
      one plant genus of this mostly nondioecious plant family. 

PMID- 24299419
TI  - Recovery of DNA barcodes from blackfly museum specimens (Diptera: Simuliidae)
      using primer sets that target a variety of sequence lengths.
AB  - In this study, we evaluated the efficacy of various primers for the purpose of
      DNA barcoding old, pinned museum specimens of blackflies (Diptera: Simuliidae).
      We analysed 271 pinned specimens representing two genera and at least 36 species.
      Due to the age of our material, we targeted overlapping DNA fragments ranging in
      size from 94 to 407 bp. We were able to recover valid sequences from 215
      specimens, of which 18% had 500- to 658-bp barcodes, 36% had 201- to 499-bp
      barcodes and 46% had 65- to 200-bp barcodes. Our study demonstrates the
      importance of choosing suitable primers when dealing with older specimens and
      shows that even very short sequences can be diagnostically informative provided
      that an appropriate gene region is used. Our study also highlights the lack of
      knowledge surrounding blackfly taxonomy, and we briefly discuss the need for
      further phylogenetic studies in this socioeconomically important family of
      insects.

PMID- 24299420
TI  - In vitro synthesis of tensioned synoviocyte bioscaffolds for meniscal
      fibrocartilage tissue engineering.
AB  - BACKGROUND: Meniscal injury is a common cause of lameness in the dog. Tissue
      engineered bioscaffolds may be a treatment option for meniscal incompetency, and
      ideally would possess meniscus- like extracellular matrix (ECM) and withstand
      meniscal tensile hoop strains. Synovium may be a useful cell source for meniscal
      tissue engineering because of its natural role in meniscal deficiency and its in
      vitro chondrogenic potential. The objective of this study is to compare meniscal 
      like extracellular matrix content of hyperconfluent synoviocyte cell sheets
      ("HCS") and hyperconfluent synoviocyte sheets which have been tensioned over wire
      hoops (tensioned synoviocyte bioscaffolds, "TSB") and cultured for 1 month.
      RESULTS: Long term culture with tension resulted in higher GAG concentration,
      higher chondrogenic index, higher collagen concentration, and type II collagen
      immunoreactivity in TSB versus HCS. Both HCS and TSB were immunoreactive for type
      I collagen, however, HCS had mild, patchy intracellular immunoreactivity while
      TSB had diffuse moderate immunoreactivity over the entire bisocaffold. The tissue
      architecture was markedly different between TSB and HCS, with TSB containing
      collagen organized in bands and sheets. Both HCS and TSB expressed alpha smooth
      muscle actin and displayed active contractile behavior. Double stranded DNA
      content was not different between TSB and HCS, while cell viability decreased in
      TSB. CONCLUSIONS: Long term culture of synoviocytes with tension improved
      meniscal- like extra cellular matrix components, specifically, the total collagen
      content, including type I and II collagen, and increased GAG content relative to
      HCS. Future research is warranted to investigate the potential of TSB for
      meniscal tissue engineering.

PMID- 24299422
TI  - Chronic pulmonary aspergillosis.
AB  - Chronic pulmonary aspergillosis (CPA) is a group of consuming diseases usually
      presenting with prolonged and relapsing cough, dyspnoea and weight loss. Acute
      symptoms such as haemoptysis and bronchial or pulmonary haemorrhage may
      occasionally occur. CPA affects patients with underlying pulmonary conditions,
      for example, chronic obstructive pulmonary disease or mycobacteriosis or common
      immunosuppressive conditions such as diabetes. Precise epidemiology is unknown,
      and while prevalence is considered low the chronic and relapsing nature of the
      disease challenges the treating physician. Diagnostics largely rely on serologic
      Aspergillus precipitins and findings on thoracic computed tomography. The latter
      are manifold comprising cavity formation, pleural involvement and sometimes
      aspergilloma. Other markers for aspergillosis are less helpful, in part due to
      the non- or semi-invasive nature of these forms of Aspergillus infection. Various
      antifungals were shown to be effective in CPA treatment. Azoles are the most
      frequently applied antifungals in the outpatient setting, but are now compromised
      by findings of Aspergillus resistance. Long-term prognosis is not fully
      elucidated and may be driven by the underlying morbidities. Prospective registry
      type studies may be suitable to systematically broaden our CPA knowledge base.
      This article gives an overview of the available literature and proposes a
      clinical working algorithm for CPA management. 

PMID- 24299421
TI  - Heterozygous FA2H mutations in autism spectrum disorders.
AB  - BACKGROUND: Widespread abnormalities in white matter development are frequently
      reported in cases of autism spectrum disorders (ASD) and could be involved in the
      disconnectivity suggested in these disorders. Homozygous mutations in the gene
      coding for fatty-acid 2-hydroxylase (FA2H), an enzyme involved in myelin
      synthesis, are associated with complex leukodystrophies, but little is known
      about the functional impact of heterozygous FA2H mutations. We hypothesized that
      rare deleterious heterozygous mutations of FA2H might constitute risk factors for
      ASD. METHODS: We searched deleterious mutations affecting FA2H, by genotyping
      1256 independent patients with ASD genotyped using Genome Wide SNP arrays, and
      also by sequencing in independent set of 186 subjects with ASD and 353 controls.
      We then explored the impact of the identified mutations by measuring FA2H
      enzymatic activity and expression, in transfected COS7 cells. RESULTS: One
      heterozygous deletion within 16q22.3-q23.1 including FA2H was observed in two
      siblings who share symptoms of autism and severe cognitive impairment, axial T2
      FLAIR weighted MRI posterior periventricular white matter lesions. Also, two rare
      non-synonymous mutations (R113W and R113Q) were reported. Although predictive
      models suggested that R113W should be a deleterious, we did not find that FA2H
      activity was affected by expression of the R113W mutation in cultured COS cells.
      CONCLUSIONS: While our results do not support a major role for FA2H coding
      variants in ASD, a screening of other genes related to myelin synthesis would
      allow us to better understand the role of non-neuronal elements in ASD
      susceptibility.

PMID- 24299423
TI  - Chemical excision of tetrahedral FeSe(2) chains from the superconductor FeSe:
      synthesis, crystal structure, and magnetism of Fe(3)Se(4)(en)(2).
AB  - Fragments of the superconducting FeSe layer, FeSe2 tetrahedral chains, were
      stabilized in the crystal structure of a new mixed-valent compound Fe3Se4(en)2
      (en = ethylenediamine) synthesized from elemental Fe and Se. The FeSe2 chains are
      separated from each other by means of Fe(en)2 linkers. Mossbauer spectroscopy and
      magnetometry reveal strong magnetic interactions within the FeSe2 chains which
      result in antiferromagnetic ordering below 170 K. According to DFT calculations,
      anisotropic transport and magnetic properties are expected for Fe3Se4(en)2. This
      compound offers a unique way to manipulate the properties of the Fe-Se infinite
      fragments by varying the topology and charge of the Fe-amino linkers. 

PMID- 24299424
TI  - Do patients with paranoid and disorganized schizophrenia respond differently to
      antipsychotic drugs?
AB  - OBJECTIVE: The aim of this study was to compare the differential response to
      amisulpride in patients with paranoid versus disorganized schizophrenia. METHOD:
      We reanalyzed the original data from five different randomized drug trials
      comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing
      427 paranoid and 296 disorganized patients with schizophrenia. RESULTS: Both the
      disorganized and the paranoid group showed a substantial improvement of the BPRS
      total score within the first 4 weeks. In the paranoid group, mean (+/-SD) BPRS
      reduction was 16.9 (+/-14.6) (t = 24.06, df = 426, P < 0.001) and in the
      disorganized group 17.0 (+/-15.9) (t = 18.49, df = 295, P < 0.001). An analysis
      of covariance (ancova) controlling for BPRS at baseline and the influence of
      different trial protocols showed significant differences between diagnostic
      groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid
      patients improved by 4.8 BPRS points more than disorganized patients (adjusted
      means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for
      the disorganized group. CONCLUSION: We conclude that amisulpride is effective in
      disorganized as well as in paranoid schizophrenia, but that symptom reduction in
      the disorganized subtype is less pronounced.

PMID- 24299425
TI  - The use of an objective structured clinical examination to assess internal
      medicine residents' transfusion knowledge.
AB  - BACKGROUND: Previous studies have indicated that medical trainees receive
      inadequate instruction in transfusion medicine and that this translates into
      insufficient transfusion knowledge throughout medical practice. We undertook to
      assess transfusion knowledge among internal medicine trainees in a single
      institution using a standardized oral examination case. STUDY DESIGN AND METHODS:
      A case of an adult with clear requirement for red blood cell transfusion was
      created. The case was reviewed by content experts and pilot tested on hematology
      trainees in their fifth postgraduate training year. The case was administered to
      internal medicine trainees in their first to fourth postgraduate years as part of
      a larger examination that is mandatory for all internal medicine trainees in our
      center. Scores on the transfusion case were assessed for each examinee. RESULTS:
      Seventy-three residents participated in the examination and completed the
      transfusion objective structured clinical examination (OSCE) case. The mean score
      on this case was 6.6 of 10 with 31.5% of examinees failing this case. Scores did
      not differ as a function of increasing years of training. CONCLUSION: This study
      again indicated that transfusion knowledge is poor among internal medicine
      trainees and that this does not improve with increasing number of years of
      training. Innovative strategies for transfusion education are urgently needed and
      should be rigorously assessed for efficacy.

PMID- 24299426
TI  - 4-Aminothiophenol functionalized gold nanoparticle-based colorimetric sensor for
      the determination of nitramine energetic materials.
AB  - The heterocyclic nitramine compounds, hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), are two most
      important military-purpose high explosives. Differentiation of RDX and HMX with
      colorimetric methods of determination has not yet been made because of their
      similar chemical structures. In this study, a sensitive colorimetric method for
      the determination of RDX and HMX was proposed on the basis of differential
      kinetics in the hydrolysis of the two compounds (yielding nitrite as a product)
      followed by their colorimetric determination using 4-aminothiophenol (4-ATP)
      modified gold nanoparticles (AuNPs) and naphthylethylene diamine (NED) as
      coupling agent for azo-dye formation, abbreviated as "4-ATP-AuNP+NED"
      colorimetric method. After alkaline hydrolysis in a 1 M Na2CO3 + 0.04 M NaOH
      mixture solution at room temperature, only RDX (but not HMX) was hydrolyzed to
      give a sufficient colorimetric response in neutralized solution, the molar
      absorptivity (epsilon) at 565 nm and the limit of detection (LOD) for RDX being
      (17.6 +/- 1.3) * 10(3) L mol(-1) cm(-1) and 0.55 MUg mL(-1), respectively. On the
      other hand, hot water bath (at 60  degrees C) hydrolysis enabled both nitramines,
      RDX and HMX, to give substantial colorimetric responses; i.e., epsilon and LOD
      for RDX were (32.8 +/- 0.5) * 10(3) L mol(-1)cm(-1) and 0.20 MUg mL(-1) and for
      HMX were (37.1 +/- 2.8) * 10(3) L mol(-1)cm(-1) and 0.24 MUg mL(-1),
      respectively. Unlike other AuNP-based nitrite sensors in the literature showing
      absorbance quenching within a relatively narrow concentration range, the
      developed sensor operated with an absorbance increase over a wide range of
      nitrite. Synthetic mixtures of (RDX + HMX) gave additive responses, and the
      proposed method was statistically validated against HPLC using nitramine
      mixtures. 

PMID- 24299427
TI  - Impact of Roux-en-Y gastric bypass on metabolic syndrome and insulin resistance
      parameters.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a complex association of clustering
      metabolic factors that increase risk of type 2 diabetes mellitus (T2DM) and
      cardiovascular disease. Surgical treatment has become an important tool to
      achieve its control. The aim of this study was to evaluate the impact of Roux-en
      Y gastric bypass (RYGB) on MetS and its individual components, clinical
      characteristics, and biochemical features. SUBJECTS AND METHODS: The study is a
      retrospective cohort of 96 subjects with MetS who underwent RYGB and were
      evaluated at baseline and after surgery. Clinical and biochemical features were
      analyzed. RESULTS: After surgery, significant rates of resolution for MetS
      (88.5%), T2DM (90.6%), hypertension (85.6%), and dyslipidemias (54.2%) were
      found. Significant decreases in levels of fasting glucose, fasting insulin,
      hemoglobin A1c, low-density lipoprotein, and triglycerides and an increase in
      high-density lipoprotein level were also shown. The decrease in insulin
      resistance evaluated by homeostasis model assessment (HOMA-IR) was consistent.
      MetS resolution was associated with postoperative glycemic control, decreases in
      levels of fasting glucose, hemoglobin A1c, HOMA-IR, and triglycerides and in
      antihypertensive usage, and percentage weight loss. CONCLUSIONS: This study found
      high rates of resolution for MetS, T2DM, hypertension, and dyslipidemias after
      RYGB in obese patients. This finding was consistent with current literature.
      Hence RYGB should be largely indicated for this group of subjects as it is a safe
      and powerful tool to achieve MetS control.

PMID- 24299428
TI  - Making a case for telehealth: measuring the carbon cost of health-related travel.
AB  - BACKGROUND: Telehealth services are promoted to reduce the cost of travel for
      people living in rural areas. The previous Australian Government, through the
      national Digital Economy Strategy, invested heavily in telehealth service
      development, at the same time introducing a carbon pricing mechanism. In planning
      a range of new telehealth services to a rural community the authors sought to
      quantify the travel conducted by people from one rural area in Australia to
      access health care, and to calculate the associated carbon emissions. METHODS: A
      population survey was conducted over a 1-week period of health-related travel
      events for the year 1 July 2011 to 30 June 2012 of all households on King Island,
      a community situated between the Australian mainland state of Victoria and the
      state of Tasmania. Validated emissions calculators were sourced from the Carbon
      Neutral website, including the vehicle and fuel use calculator and air travel
      carbon calculator, to calculate the total emissions associated with the fuel
      burned in tonnes of carbon dioxide equivalent (tCO2e). RESULTS: Thirty nine
      percent of the population (625 participants) reported a total of 511 healthcare
      related travel events. Participants travelled a total of 346 573 km and generated
      0.22 tCO2e per capita. Participants paid the cost of their own travel more than
      70% of the time. CONCLUSIONS: Dependence on fossil fuels for transport in a
      carbon economy has a significant impact on total healthcare carbon emissions.
      Alternative models of care, such as telehealth, need be developed for an
      environmentally sustainable healthcare system for rural and remote areas.

PMID- 24299429
TI  - Saving lives of patients with adrenal insufficiency: a pan-European initiative?

PMID- 24299430
TI  - Studying weak and dynamic interactions of posttranslationally modified proteins
      using expressed protein ligation.
AB  - Many cellular processes are regulated by posttranslational modifications that are
      recognized by specific domains in protein binding partners. These interactions
      are often weak, thus allowing a highly dynamic and combinatorial regulatory
      network of protein-protein interactions. We report an efficient strategy that
      overcomes challenges in structural analysis of such a weak transient interaction
      between the Tudor domain of the Survival of Motor Neuron (SMN) protein and
      symmetrically dimethylated arginine (sDMA). The posttranslational modification is
      chemically introduced and covalently linked to the effector module by a one-pot
      expressed protein ligation (EPL) procedure also enabling segmental incorporation
      of NMR-active isotopes for structural analysis. Covalent coupling of the two
      interacting moieties shifts the equilibrium to the bound state, and
      stoichiometric interactions are formed even for low affinity interactions. Our
      approach should enable the structural analysis of weak interactions by NMR or X
      ray crystallography to better understand the role of posttranslational
      modifications in dynamic biological processes. 

PMID- 24299431
TI  - Thinning and rupture of liquid films by moving slot jets.
AB  - We present systematic experiments of the rupture and dewetting of thin films of a
      nonvolatile polar liquid on partially wetting substrates due to a moving slot
      jet, which impinges at normal incidence. The relative motion was provided by a
      custom-built spin coater with a bidirectionally accessible axis of rotation that
      enabled us to measure film thickness profiles in situ as a function of substrate
      velocity using dual-wavelength interference microscopy. On partially wetting
      polymeric substrates, dry spots form in liquid films with a residual thickness
      well below 1 MUm. We measured the density of dry spots as well as the density and
      size distribution of the residual droplets as a function of film thickness. In a
      certain parameter range, the droplet distributions exhibit pronounced anisotropy
      due to the effect of long-range shear stresses on the dewetting rim instability.
      We find robust power-law scaling relations over a large range of film thicknesses
      and a striking similarity to literature data obtained with ultrathin polymer melt
      layers on silicon substrates. 

PMID- 24299432
TI  - Integrating rural health services.

PMID- 24299433
TI  - Close the gap for vision: The key is to invest on coordination.
AB  - OBJECTIVE: The study aims to estimate costs required for coordination and case
      management activities support access to treatment for the three most common eye
      conditions among Indigenous Australians, cataract, refractive error and diabetic
      retinopathy. DESIGN: Coordination activities were identified using in-depth
      interviews, focus groups and face-to-face consultations. Data were collected at
      21 sites across Australia. The estimation of costs used salary data from relevant
      government websites and was organised by diagnosis and type of coordination
      activity. SETTING: Urban and remote regions of Australia. INTERVENTIONS: Needs
      based provision support services to facilitate access to eye care for cataract,
      refractive error and diabetic retinopathy to Indigenous Australians. MAIN OUTCOME
      MEASURES: Cost (AUD$ in 2011) of equivalent full time (EFT) coordination staff.
      RESULTS: The annual coordination workforce required for the three eye conditions
      was 8.3 EFT staff per 10 000 Indigenous Australians. The annual cost of eye care
      coordination workforce is estimated to be AUD$21 337 012 in 2011. CONCLUSIONS:
      This innovative, 'activity-based' model identified the workforce required to
      support the provision of eye care for Indigenous Australians and estimated their
      costs. The findings are of clear value to government funders and other decision
      makers. The model can potentially be used to estimate staffing and associated
      costs for other Indigenous and non-Indigenous health needs.

PMID- 24299434
TI  - Issues that impact on Aboriginal health workers' and registered nurses' provision
      of diabetes health care in rural and remote health settings.
AB  - Type 2 diabetes mellitus is an established health problem for Indigenous
      Australians. One strategy to address this issue is to educate health
      professionals in diabetes management and education. OBJECTIVE: The objective of
      this paper is to identify important issues that compromise the clinical practice
      of rural and remote Aboriginal health workers (AHWs) and registered nurses (RNs)
      who undertook an accredited Australian Diabetes Educators Association diabetes
      course and to suggest strategies to improve practice. DESIGN: The design used a
      qualitative approach and discussion schedule to elicit responses. SETTING: The
      setting involved two Aboriginal community controlled and seven mainstream health
      services in the Far Western region of New South Wales. PARTICIPANTS: The
      participants were experienced diabetes educators (RNs and AHWs), managers and
      students currently enrolled in the course (n = 17). RESULTS: The results
      indicated issues that compromise diabetes practice and identified strategies to
      improve practice. Issues were: the confusing funding practices by health
      providers, the duplication of health services, the lack of recognition of
      diabetes qualifications and the transient nature of Indigenous people. Strategies
      included the need for: continuous dedicated diabetes health funding, a role
      clarification for diabetes educators, strategic diabetes planning and the
      importance of diabetes educators working in partnership. CONCLUSION: The
      conclusion from this study indicates that if the delivery of diabetes health
      services to Indigenous Australians is to improve it is necessary to address these
      identified issues.

PMID- 24299435
TI  - Addressing chronic kidney disease in Far North Queensland: gains and
      opportunities.
AB  - OBJECTIVE: To determine whether people seen by the Far North Queensland
      Specialist Medical Outreach Service (SMOS) with chronic kidney disease (CKD) and
      proteinuria were treated according to established guidelines. DESIGN: Audit of
      SMOS clinical reports from 18th May to 27th July 2012. Clinical markers were
      compared with the Caring for Australians with Renal Impairment and National Heart
      Foundation management guidelines. SETTING: Reports covering primary health care
      centres located in remote communities of Cape York Peninsula and Torres Strait,
      Far North Queensland. MAIN OUTCOME MEASURE(S): The proportion of people with CKD
      and proteinuria on appropriate renoprotective treatment with an angiotensin
      converting enzyme inhibitor (ACE-inhibitor) or angiotensin-2 receptor blocker
      (ARB). The proportion of people with CKD and proteinuria reaching blood pressure
      targets as per National Heart Foundation guidelines. The proportion of people
      with stage 4 CKD appropriately referred to a specialist renal service. RESULTS:
      One hundred and eighty-six clinical reports were reviewed; 48 people had markers
      of CKD. Forty-five of the 48 (94%) had been prescribed an ACE-inhibitor or ARB
      according to management guidelines. Nineteen of the 48 (40%) had blood pressures
      within the target range. Four of six people with late-stage CKD (stage 4 or 5)
      had been referred to a specialist renal service. CONCLUSIONS: This audit confirms
      the high rate of CKD in the people of Far North Queensland, although this is a
      highly selected sample. It shows appropriate prescribing of renoprotective
      treatment in most cases. However, it also highlights the need for a more vigorous
      approach to blood pressure control.

PMID- 24299436
TI  - Reduction of gastric cancer mortality by endoscopic and radiographic screening in
      an isolated island: A retrospective cohort study.
AB  - OBJECTIVE: To evaluate the efficacy of endoscopic and radiographic screening for
      gastric cancer. DESIGN: A retrospective cohort study. SETTING: Community in an
      isolated island. PARTICIPANTS: The study involved 186 patients (131 men, 55
      women) diagnosed with gastric cancer between 2000 and 2005. INTERVENTIONS:
      Endoscopic and radiographic screening. MAIN OUTCOME MEASUREMENTS: The odds ratio
      of death from gastric cancer in participants versus non-participants of
      screening, the cumulative survival rate of the gastric cancer patients. RESULTS:
      The odds ratio of death from gastric cancer in the participants versus non
      participants of screening was 0.091 (95% confidence interval (CI) 0.027-0.308; P
      < 0.0001). The cumulative survival rate of the gastric cancer patients in the
      screening group was higher than that in the non-screening group (P < 0.0001). In
      the endoscopic screening district, the odds ratio of death from gastric cancer
      among the participants versus non-participants of endoscopic screening was 0.117
      (95% CI 0.013-1.056; P = 0.0525), while in the radiographic screening district,
      it was 0.086 (95% CI 0.020-0.376; P < 0.0001). The cumulative survival rates were
      higher in both the screening groups as compared with the non-screening group
      (endoscopy, P = 0.0302; radiography, P = 0.0012). CONCLUSION: The results suggest
      that both radiographic and endoscopic screening may prevent gastric cancer
      deaths.

PMID- 24299437
TI  - Outreach surgical consulting services in North East Victoria.
AB  - OBJECTIVE: There is a paucity of data regarding the provision of consultative
      outreach specialist surgical services to rural areas. This paper aims to describe
      a model of outreach consultative practice to deliver specialist surgical services
      to rural communities. DESIGN: Analysis of prospectively collected data for
      consultations in a three month period for two surgeons based in Wangaratta.
      SETTING: Two surgeons in regional Victoria based in Wangaratta, North East
      Victoria, conducting outreach consultations to Beechworth, Benalla, Bright and
      Mansfield. PARTICIPANTS: All patients seen in consultations over a 3-month
      period. MAIN OUTCOME MEASURES: Patient workload, casemix of presenting complaint,
      consultation outcome including plan for surgical procedure. RESULTS: Outreach
      surgical consulting was associated with a higher proportion of new consultations,
      and there was trend towards being more likely to result in a surgical procedure
      than consultations in the base rural centre. CONCLUSIONS: Outreach surgical
      consulting provides surgeons with a larger referral base and provides communities
      with better access to local specialists. Outreach practice should be encouraged
      for surgeons in regional centres.

PMID- 24299438
TI  - Cost of close the gap for vision of Indigenous Australians: On estimating the
      extra resources required.
AB  - OBJECTIVE: To estimate the costs of the extra resources required to close the gap
      of vision between Indigenous and non-Indigenous Australians. DESIGN: Constructing
      comprehensive eye care pathways for Indigenous Australians with their related
      probabilities, to capture full eye care usage compared with current usage rate
      for cataract surgery, refractive error and diabetic retinopathy using the best
      available data. SETTING: Urban and remote regions of Australia. INTERVENTIONS:
      The provision of eye care for cataract surgery, refractive error and diabetic
      retinopathy. MAIN OUTCOME MEASURES: Estimated cost needed for full access,
      estimated current spending and estimated extra cost required to close the gaps of
      cataract surgery, refractive error and diabetic retinopathy for Indigenous
      Australians. RESULTS: Total cost needed for full coverage of all three major eye
      conditions is $45.5 million per year in 2011 Australian dollars. Current annual
      spending is $17.4 million. Additional yearly cost required to close the gap of
      vision is $28 million. This includes extra-capped funds of $3 million from the
      Commonwealth Government and $2 million from the State and Territory Governments.
      Additional coordination costs per year are $13.3 million. CONCLUSIONS: Although
      available data are limited, this study has produced the first estimates that are
      indicative of the need for planning and provide equity in eye care.

PMID- 24299439
TI  - Psychometric evaluation of a Korean version of the 8-item Medication Adherence
      Scale in rural older adults with hypertension.
AB  - OBJECTIVE: To examine the psychometric properties of a structured self-reported 8
      item Korean-version Morisky Medication Adherence Scale (MMAS-K) among rural older
      adults with hypertension. DESIGN: Cross-sectional descriptive survey. SETTING: A
      rural community comprising three primary health care posts in Gangwon Province,
      South Korea. PARTICIPANTS: Ninety-two older adults with hypertension who received
      treatment at primary health care posts. MAIN OUTCOME MEASURES: Participants
      completed an 8-item MMAS-K questionnaire, and the community health practitioners
      manually measured blood pressure. Factor analysis and correlation coefficient for
      validity and the Kuder-Richardson alpha coefficient for reliability of the MMAS-K
      were used, while the association between medication adherence and blood pressure
      control was determined using Fisher's exact test. RESULTS: Internal consistency
      reliability was acceptable with a coefficient alpha of 0.71. The factor analysis
      of construct validity identified two dimensions of the 8-item MMAS-K, explaining
      52.22% of the total variance. There was a high correlation between the 8-item
      MMAS-K and the original 4-item MMAS (r = 0.874), indicating that these scales
      measure theoretically related constructs for convergent validity. There was a
      significant association between the 8-item MMAS-K score and blood pressure
      control (P < 0.05), indicating that, for the known-groups validity, the
      controlled blood pressure group was more likely to have higher rate of medication
      adherence than the poor-control group. CONCLUSIONS: The findings indicate a
      positive association between medication adherence and blood pressure control. The
      8-item MMAS-K possesses adequate validity and reliability among rural older
      adults with hypertension.

PMID- 24299440
TI  - Improving osteoporosis management following minimal trauma fracture in a regional
      setting: The Coffs Fracture Card Project.
AB  - OBJECTIVES: To improve osteoporosis (OSP) management following minimal trauma
      fracture (MTF) with few additional resources. DESIGN: Population intervention
      with serial cross-sectional analysis. SETTING: Regional setting involving primary
      care, base hospital and private hospital. PARTICIPANTS: Patients with MTF.
      INTERVENTION: A 'Fracture Card' prompting OSP management was provided to all
      patients post-MTF. Patients were encouraged to attend their general practitioner
      (GP) with this to discuss bone health issues. The 2-year intervention was
      supported by a public health education campaign. MAIN OUTCOME MEASURES: Number of
      (i) serum 25-OH vitamin D assays, (ii) dual-energy X-ray absorptiometry (DXA)
      scans, and (iii) new Pharmaceutical Benefits Scheme (PBS)-subsidised
      prescriptions for bone protective therapy (bisphosphonates, raloxifene,
      strontium, teriparatide, denosumab). RESULTS: The number of serum 25-OH vitamin D
      assays ordered in Coffs Harbour increased from 329 +/- 15 per month (July 2009
      June 2010) to 568 +/- 21 (July 2010-June 2012; P < 0.001). The number of DXA
      scans performed per month increased from 192 +/- 14 (July 2009-June 2010) to 296
      +/- 12 (July 2010-June 2012; P < 0.001). There was no difference in the number of
      new PBS-subsidised prescriptions for bone protective therapy in the Coffs
      statistical subdivision over that time (176 +/- 3.8 per month, July 2009-June
      2010 versus 180 +/- 3.5, July 2010-June 2012, P > 0.05). CONCLUSIONS: The
      intervention was associated with an increased number of 25-OH vitamin D assays
      and DXA scans but not with more prescriptions for bone protective therapy. This
      suggests that a public health education campaign and provision of a 'prompt' for
      GPs was only partially successful at improving OSP management post-MTF. This has
      driven establishment of a Fracture Liaison Service.

PMID- 24299441
TI  - Reporting of non-prescribed medication usage in remote Australia: health-seeking
      habits in Port Headland.

PMID- 24299442
TI  - Variation in religious affiliations between metropolitan, rural, agricultural and
      elderly populations: An update.

PMID- 24299444
TI  - Are high-care nursing home residents at greater risk of unplanned hospital
      admission than other elderly patients when exposed to Beers potentially
      inappropriate medications?
AB  - AIM: To compare the risk of unplanned hospitalization in high-care nursing home
      residents taking Beers potentially inappropriate medications (PIM) against that
      of other elderly. METHODS: Using an enhanced case-time-control design and
      conditional logistic regression applied to the pharmaceutical claims and other
      linked data of 245436 Western Australians aged >= 65 years (1993-2005), the study
      derived odds ratios for unplanned hospitalization in each group, from which
      attributable fractions, numbers, proportions and rates of PIM-related admissions
      were derived. RESULTS: Overall, 383150 unplanned hospitalizations were
      identified. PIM exposure was associated with a similar proportional increase in
      unplanned hospitalizations in high-care nursing home residents as in other older
      people; adjusted OR 1.21 (95% CI 1.10-1.34; attributable fraction 17.5%) versus
      OR 1.19 (95% CI 1.16-1.21; attributable fraction 15.7%). However, high-care
      nursing home residents had much higher estimated rates of hospitalizations
      attributed to Beers medications than other elderly (3951 vs 1394 per 100000
      person-years). The relative risk of unplanned hospitalization rose similarly in
      both groups with increasing numbers of different PIM taken (OR 5.1 for 10 vs 0
      PIM), but was affected more markedly by 3-month PIM consumption in nursing home
      residents (OR 4.85, 95% CI 2.40-9.83 for 900 vs 0 PIM daily doses) than in other
      older adults (OR 2.10, 95% CI 1.73-2.55). CONCLUSIONS: High-care nursing home
      residents do not appear to have a greater relative risk of unplanned
      hospitalization when given PIM, but do incur a higher absolute burden than other
      older adults. Physicians should exert caution with Beers medications in all older
      patients, restricting the number of different PIM and PIM quantity prescribed
      whenever possible.

PMID- 24299445
TI  - The role of hydrolysates for atopy prevention--con.

PMID- 24299446
TI  - Immediate adhesive properties to dentin and enamel of a universal adhesive
      associated with a hydrophobic resin coat.
AB  - OBJECTIVES: To evaluate the effect of acid etching and application of a
      hydrophobic resin coat on the enamel/dentin bond strengths and degree of
      conversion (DC) within the hybrid layer of a universal adhesive system (G-Bond
      Plus [GB]). METHODS: A total of 60 extracted third molars were divided into four
      groups for bond-strength testing, according to the adhesive strategy: GB applied
      as a one-step self-etch adhesive (1-stepSE); GB applied as in 1-stepSE followed
      by one coat of the hydrophobic resin Heliobond (2-stepSE); GB applied as a two
      step etch-and-rinse adhesive (2-stepER); GB applied as in 2-stepER followed by
      one coat of the hydrophobic resin Heliobond (3-stepER). There were 40 teeth used
      for enamel microshear bond strength (MUSBS) and DC; and 20 teeth used for dentin
      microtensile bond strength (MUTBS) and DC. After restorations were constructed,
      specimens were stored in water (37 degrees C/24 h) and then tested at 0.5 mm/min
      (MUTBS) or 1.0 mm/min (MUSBS). Enamel-resin and dentin-resin interfaces from each
      group were evaluated for DC using micro-Raman spectroscopy. Data were analyzed
      with two-way analysis of variance for each substrate and the Tukey test
      (alpha=0.05). RESULTS: For enamel, the use of a hydrophobic resin coat resulted
      in statistically significant higher mean enamel MUSBS only for the ER strategy (3
      stepER vs 2-stepER, p<0.0002). DC was significantly improved for the SE strategy
      (p<0.00002). For dentin, the use of a hydrophobic resin coat resulted in
      significantly higher dentin mean MUTBS only for the SE strategy (2-stepSE vs 1
      stepSE, p<0.0007). DC was significantly improved in groups 2-stepSE and 3-stepER
      when compared with 1-stepSE and 2-stepER, respectively (p<0.0009). CONCLUSIONS:
      The use of a hydrophobic resin coat may be beneficial for the selective enamel
      etching technique, because it improves bond strengths to enamel when applied with
      the ER strategy and to dentin when used with the SE adhesion strategy. The
      application of a hydrophobic resin coat may improve DC in resin-dentin interfaces
      formed with either the SE or the ER strategy. On enamel, DC may benefit from the
      application of a hydrophobic resin coat over 1-stepSE adhesives.

PMID- 24299447
TI  - Effects of different surface treatments on bond strength between resin cements
      and zirconia ceramics.
AB  - This study compares the bond strength of resin cement and yttrium-stabilized
      tetragonal zirconia polycrystalline (Y-TZP) ceramic with different surface
      conditioning methods. Two hundred presintered Y-TZP ceramic specimens were
      prepared, sintered (4 * 4 * 4 mm), and randomly assigned to four equal groups as
      control (C, no conditioning); airborne particle abraded (APA, air abrasion with
      11 MUm Al2O3); tribochemical silica coating/silane coupling system (TSC, Rocatec,
      air abrasion with 110 MUm Al2O3, 30 MUm silica-coated Al2O3 and silane); and
      laser (L, Er:YAG laser irradiation treated at a power setting of 200 mJ). After
      specimen preparation, composite resin cylinders were prepared and cemented with
      resin cements (Clearfil Esthetic, Panavia F 2.0, Rely X-U100, Super Bond C&B, and
      Multilink Automix) on the ceramic surfaces and kept in an incubator at 37 degrees
      C for 60 days. All specimens were tested for shear bond strength with a universal
      testing machine, and fractured surfaces were evaluated by environmental scanning
      electron microscopy. Statistical analysis was performed using Kruskal-Wallis and
      Mann-Whitney U-tests (alpha=0.05). The bond strengths for C and L groups were not
      significantly different according to adhesive resin cement. APA and TSC resulted
      in increased bond strength for Panavia F 2.0 and Rely X-U100 resin cements.
      Additionally, TSC presented higher bond strength with Multilink Automix. Adhesive
      fracture between the ceramic and resin cement was the most common failure.
      Complete cohesive fracture at the ceramic or composite cylinders was not
      observed. Regardless of the adhesive resin cement used, laser treatment did not
      improve resin bond strength.

PMID- 24299448
TI  - Four-component supramolecular nanorotors.
AB  - A family of supramolecular four-component nanorotors was quantitatively self
      assembled from two different zinc(II) porphyrins: one representing the stator and
      the other the rotator with DABCO as an interconnecting axle and copper(I) ions.
      Rotational spinning in ROT-1' occurs at 97,000 s(-1) at 25  degrees C but is
      virtually stopped at -75  degrees C. The activation vs binding data suggest that
      spinning is an intrasupramolecular process occurring to >99.9% without
      dissociation. Addition and removal of two further equiv of Cu(+) reversibly
      switches the mode of the stochastic rotation between pure 180 degrees  and mixed
      90 degrees /180 degrees  steps and reversibly regulates the speed between 97,000
      and ~80,000 s(-1).

PMID- 24299449
TI  - Atmospheric chemistry of CF3CF2CHO: absorption cross sections in the UV and IR
      regions, photolysis at 308 nm, and gas-phase reaction with OH radicals (T = 263
      358 K).
AB  - The relative importance in the atmosphere of UV photolysis of
      perfluoropropionaldehyde, CF3CF2CHO, and reaction with hydroxyl (OH) radicals has
      been investigated in this work. First, the forbidden n -> pi* transition of the
      carbonyl chromophore was characterized between 230 and 380 nm as a function of
      temperature (269-298 K) and UV absorption cross sections, sigmalambda, were
      determined in those ranges. In addition, IR absorption cross sections were
      determined between 4000 and 500 cm-1. Pulsed laser photolysis (PLP) of CF3CF2CHO
      coupled to Fourier transform infrared (FTIR) was employed to determine the
      overall photolysis quantum yield, Philambda, at 308 nm and 298 K. Philambda=308
      nm was pressure dependent, ranging from (0.94 +/- 0.14) at 75 Torr to (0.30 +/-
      0.01) at 760 Torr. This dependence is characterized by the Stern-Volmer
      parameters Phi0lambda=308 nm = (1.19 +/- 0.34) and KSV = (1.22 +/- 0.52) * 10(
      19) cm3 molecule-1. End products of the photodissociation of CF3CF2CHO were
      measured and quantified by FTIR spectroscopy. Furthermore, the rate coefficients
      for the OH + CF3CF2CHO reaction, k1, were determined as a function of temperature
      (T = 263-358 K) by PLP-LIF. At room temperature the rate coefficient is k1(T =
      298 K) = (5.57 +/- 0.07) * 10(-13) cm3 molecule-1 s-1, whereas the temperature
      dependence is described by k1(T) = (2.56 +/- 0.32) * 10(-12) exp{-(458 +/- 36)/T}
      cm3 molecule-1 s-1. On the basis of our results, photolysis of CF3CF2CHO in the
      actinic region could be an important removal process for CF3CF2CHO in the
      atmosphere. The formation of the primary products in the UV photolysis of
      CF3CF2CHO is also discussed.

PMID- 24299450
TI  - Parentage and sibship inference from markers in polyploids.
AB  - Many plants and some animal species are polyploids. Nondisomically inherited
      markers (e.g. microsatellites) in such species cannot be analysed directly by
      standard population genetics methods developed for diploid species. One solution
      is to transform the polyploid codominant genotypes to pseudodiploid-dominant
      genotypes, which can then be analysed by standard methods for various purposes
      such as spatial genetic structure, individual relatedness and relationship.
      Although this data transformation approach has been used repeatedly in the
      literature, no systematic study has been conducted to investigate how efficient
      it is, how much marker information is lost and thus how much analysis accuracy is
      reduced. More specifically, it is unknown whether or not the transformed data can
      be used to infer parentage and sibship jointly, and how different sampling
      schemes (number and polymorphism of markers, number of individuals) and ploidy
      level affect the inference accuracy. This study analyses both simulated and
      empirical data to examine the effects of polyploid levels, actual pedigree
      structures and marker number and polymorphism on the accuracy of joint parentage
      and sibship assignments in polyploid species. We show that sibship, parentage and
      selfing rates in polyploids can be inferred accurately from a typical set of
      microsatellite loci. We also show that inferences can be substantially improved
      by allowing for a small genotyping error rate to accommodate the distortion in
      assumed Mendelian inheritance of the converted markers when large sibship groups
      are involved. The results are discussed in the context of polyploid data analysis
      in molecular ecology. 

PMID- 24299451
TI  - Atypical fibroxanthoma arising in a young patient with Li-Fraumeni syndrome.
AB  - Patients with Li-Fraumeni syndrome (LFS) have a germ-line mutation of p53 (TP53)
      and are predisposed to develop a variety of malignancies at an early age. In this
      report, we describe an 18-year-old woman with LFS who developed an atypical
      fibroxanthoma (AFX) on her left arm. This tumor was based in the dermis, sparsely
      cellular and had ill-defined borders. It was composed predominantly of medium
      sized spindled-shaped cells, but many large cells with pleomorphic nuclei were
      also present. Immunohistochemical stains showed that the tumor cells lacked
      expression of keratin, S-100 protein, desmin and CD34. Array-based comparative
      genomic hybridization (aCGH) revealed marked genomic instability with multiple
      whole chromosome losses, including chromosomes 8, 10, 13 and 22, as well as a
      partial loss of 17p. This represents one of a few reports of a cutaneous tumor in
      a patient with LFS and a rare example of an AFX occurring at a young age. 

PMID- 24299453
TI  - A new bead-based human platelet antigen antibodies detection assay versus the
      monoclonal antibody immobilization of platelet antigens assay.
AB  - BACKGROUND: The performance of a newly developed Luminex bead-based platelet
      (PLT) antibody detection method (PAKLx) was compared with the monoclonal antibody
      immobilization of PLT antigens (MAIPA) assay and the LifeScreen Deluxe Luminex
      bead-based HLA Class I antibody detection method (LMX). STUDY DESIGN AND METHODS:
      Six sera containing anti-human PLT antigen (HPA)-1a (n=2), HPA-1b, HPA-2b, HPA
      3a, or HPA-5b were tested in titration. A total of 194 sera, including HPA-1a, 
      1b, -2a, -2b, -3a, -5a, and -5b antibodies with or without HLA antibodies (n=63);
      glycoprotein (GP) IV antibodies (n=1); PLT autoantibodies (n=3); HLA antibodies
      (n=45); and samples with no PLT-reactive antibodies (n=82), were tested in both
      assays. RESULTS: Comparable levels of sensitivity were obtained for the MAIPA and
      PAKLx. The PAKLx showed four (6%) false-negative results in 67 sera with HPA or
      GP-reactive antibodies: anti-HPA-3a (n=1) or anti-HPA-5b (n=3). The PAKLx showed
      in 10 of the total 194 samples (5%) the presence of antibodies not detected by
      the MAIPA. This concerned broadly GP-reactive antibodies (n=7), anti-GPIIb/IIIa
      combined with anti-HPA-3a (n=1), anti-HPA-1a (borderline, n=1), and anti-GPIV
      (n=1). Testing 175 sera for anti-HLA Class I antibodies in the PAKLx and LMX
      showed four discrepant results: PAKLx negative and LMX positive, n=3 and n=1,
      respectively. CONCLUSION: For the vast majority of the specimens tested (93%) the
      results of the PAKLx were in concordance with the MAIPA. The PAKLx is a fast,
      easy to perform, and sensitive PLT antibody screening method.

PMID- 24299452
TI  - HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple
      mitochondrial respiratory chain enzymes and pyruvate dehydrogenase.
AB  - BACKGROUND: Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by
      HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of
      valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme
      deficiencies can arise from a number of mechanisms, including defective
      maintenance or expression of mitochondrial DNA. Impaired biosynthesis of iron
      sulphur clusters and lipoic acid can lead to pyruvate dehydrogenase complex
      (PDHc) deficiency in addition to multiple RC deficiencies, known as the multiple
      mitochondrial dysfunctions syndrome. METHODS: Two brothers born to distantly
      related Pakistani parents presenting in early infancy with a progressive
      neurodegenerative disorder, associated with basal ganglia changes on brain
      magnetic resonance imaging, were investigated for suspected Leigh-like
      mitochondrial disease. The index case had deficiencies of multiple RC enzymes and
      PDHc in skeletal muscle and fibroblasts respectively, but these were normal in
      his younger brother. The observation of persistently elevated hydroxy-C4
      carnitine levels in the younger brother led to suspicion of HIBCH deficiency,
      which was investigated by biochemical assay in cultured skin fibroblasts and
      molecular genetic analysis. RESULTS: Specific spectrophotometric enzyme assay
      revealed HIBCH activity to be below detectable limits in cultured skin
      fibroblasts from both brothers. Direct Sanger sequence analysis demonstrated a
      novel homozygous pathogenic missense mutation c.950G <A; p.Gly317Glu in the HIBCH
      gene, which segregated with infantile-onset neurodegeneration within the family.
      CONCLUSIONS: HIBCH deficiency, a disorder of valine catabolism, is a novel cause
      of the multiple mitochondrial dysfunctions syndrome, and should be considered in
      the differential diagnosis of patients presenting with multiple RC deficiencies
      and/or pyruvate dehydrogenase deficiency.

PMID- 24299454
TI  - Lactic acidosis induced by metformin in a chronic hemodialysis patient with
      diabetes mellitus type 2.
AB  - Metformin is a biguanide group oral antidiabetic drug used for the treatment of
      type 2 diabetes mellitus. Nausea, vomiting, diarrhea, abdominal pain, and
      anorexia are the most common adverse effects encountered during treatment. Lactic
      acidosis is a serious side effect seen with metformin use, and while the
      incidence of lactic acidosis is similar to other oral antidiabetics, metformin is
      not recommended to patients with certain risk factors, such as cardiovascular,
      pulmonary, and renal and liver failure. We describe a chronic hemodialysis
      patient treated with metformin, presenting to the nephrology department with
      altered mental status. 

PMID- 24299456
TI  - Interaction of human minichromosome maintenance protein-binding protein with
      minichromosome maintenance 2-7.
AB  - It has been reported that minichromosome maintenance protein-binding protein (MCM
      BP) functions in the formation of the pre-replication complex, unloading of
      minichromosome maintenance (MCM)2-7 from chromatin in late S phase, and formation
      of the cohesion complex by interacting with MCM3-7 proteins, suggesting that MCM
      BP functions in several different reactions during the cell cycle. Here, we
      examined the interaction of human MCM-BP with MCM2-7 and structural maintenance
      of chromosome 3 in synchronized HeLa cells by immunoprecipitation. The results
      show that MCM-BP mainly interacts with MCM7 in the Triton-soluble fraction from S
      phase and G(2) phase cells, and it also interacts with structural maintenance of
      chromosome 3 in the fraction from G(2) phase cells. In vitro studies show that
      MCM-BP disassembles MCM2-7 bound to DNA with a fork-like structure by interacting
      with MCM3, MCM5, and MCM7. These results suggest that MCM-BP functions in
      disassembling MCM2-7 on chromatin during S phase and G2 phase by interacting with
      MCM3, MCM5, and MCM7.

PMID- 24299455
TI  - Central nervous system delivery of helper-dependent canine adenovirus corrects
      neuropathology and behavior in mucopolysaccharidosis type VII mice.
AB  - Canine adenovirus type 2 vectors (CAV-2) are promising tools to treat global
      central nervous system (CNS) disorders because of their preferential transduction
      of neurons and efficient retrograde axonal transport. Here we tested the
      potential of a helper-dependent CAV-2 vector expressing beta-glucuronidase (HD
      RIGIE) in a mouse model of mucopolysaccharidosis type VII (MPS VII), a lysosomal
      storage disease caused by deficiency in beta-glucuronidase activity. MPS VII
      leads to glycosaminoglycan accumulation into enlarged vesicles in peripheral
      tissues and the CNS, resulting in peripheral and neuronal dysfunction. After
      intracranial administration of HD-RIGIE, we show long-term expression of beta
      glucuronidase that led to correction of neuropathology around the injection site
      and in distal areas. This phenotypic correction correlated with a decrease in
      secondary-elevated lysosomal enzyme activity and glycosaminoglycan levels,
      consistent with global biochemical correction. Moreover, HD-RIGIE-treated mice
      show significant cognitive improvement. Thus, injections of HD-CAV-2 vectors in
      the brain allow a global and sustained expression and may have implications for
      brain therapy in patients with lysosomal storage disease.

PMID- 24299457
TI  - Tamoxifen integromics and personalized medicine: dynamic modular transformations
      underpinning response to tamoxifen in breast cancer treatment.
AB  - Recent advances in pharmacogenomics technologies allow bold steps to be taken
      towards personalized medicine, more accurate health planning, and personalized
      drug development. In this framework, systems pharmacology network-based
      approaches offer an appealing way for integrating multi-omics data and set the
      basis for defining systems-level drug response biomarkers. On the road to
      individualized tamoxifen treatment in estrogen receptor-positive breast cancer
      patients, we examine the dynamics of the attendant pharmacological response
      mechanisms. By means of an "integromics" network approach, we assessed the
      tamoxifen effect through the way the high-order organization of interactome
      (i.e., the modules) is perturbed. To accomplish that, first we integrated the
      time series transcriptome data with the human protein interaction data, and
      second, an efficient module-detecting algorithm was applied onto the composite
      graphs. Our findings show that tamoxifen induces severe modular transformations
      on specific areas of the interactome. Our modular biomarkers in response to
      tamoxifen attest to the immunomodulatory role of tamoxifen, and further reveal
      that it deregulates cell cycle and apoptosis pathways, while coordinating the
      proteasome and basal transcription factors. To the best of our knowledge, this is
      the first report that informs the fields of personalized medicine and clinical
      pharmacology about the actual dynamic interactome response to tamoxifen
      administration.

PMID- 24299458
TI  - Trace detection of specific viable bacteria using tetracysteine-tagged
      bacteriophages.
AB  - Advanced methods are urgently needed to determine the identity and viability of
      trace amounts of pathogenic bacteria in a short time. Existing approaches either
      fall short in the accurate assessment of microbial viability or lack specificity
      in bacterial identification. Bacteriophages (or phages for short) are viruses
      that exclusively infect bacterial host cells with high specificity. As phages
      infect and replicate only in living bacterial hosts, here we exploit the strategy
      of using tetracysteine (TC)-tagged phage in combination with biarsenical dye to
      the discriminative detection of viable target bacteria from dead target cells and
      other viable but nontarget bacterial cells. Using recombinant M13KE-TC phage and
      Escherichia coli ER2738 as a model system, distinct differentiation between
      individual viable target cells from dead target cells was demonstrated by flow
      cytometry and fluorescence microscopy. As few as 1% viable E. coli ER2738 can be
      accurately quantified in a mix with dead E. coli ER2738 by flow cytometry. With
      fluorescence microscopic measurement, specific detection of as rare as 1 cfu/mL
      original viable target bacteria was achieved in the presence of a large excess of
      dead target cells and other viable but nontarget bacterial cells in 40 mL
      artificially contaminated drinking water sample in less than 3 h. This TC-phage
      FlAsH approach is sensitive, specific, rapid, and simple, and thus shows great
      potential in water safety monitoring, health surveillance, and clinical diagnosis
      of which trace detection and identification of viable bacterial pathogens is
      highly demanded. 

PMID- 24299460
TI  - A C60-templated tetrameric porphyrin barrel complex via zinc-mediated self
      assembly utilizing labile capping ligands.
AB  - Coordination-driven self-assembly utilizing labile capping ligands has been
      exploited as a novel strategy for metallo-cage containers. Herein, we report a
      tetrameric porphyrin barrel complex [C60?Zn814(H2O)4(OTs)12](OTs)4 (2) (OTs = p
      CH3C6H4SO3) formed from a tetrakis(bipyridyl)porphyrin ligand 1, Zn(OTs)2, and a
      template guest, C60 fullerene. The tetrameric-barrel 2 contains two kinds of
      bis(bpy) Zn(II) centers coordinated by TsO(-) anions which serve as labile
      capping ligands in the formation of the finite structure of 2.

PMID- 24299459
TI  - Genetic diversity of Histoplasma capsulatum strains isolated from Argentina based
      on nucleotide sequence variations in the internal transcribed spacer regions of
      rDNA.
AB  - The internal transcribed spacer (ITS) regions of rDNA genes of 49 Histoplasma
      capsulatum (48 from clinical samples and one from soil) isolates were examined.
      Nucleotide sequence heterogeneity within this region was useful for phylogenetic
      classification of H. capsulatum and species identification. Thus, in 45 of 49
      isolates we observed higher percentages of identity in the nucleotide sequences
      of ITS regions when the isolates studied herein were compared with those reported
      in our country in the South America B clade. Phylogenetic analyses of rDNA
      sequences corresponding to the 537 bp of the ITS region obtained from H.
      capsulatum isolates assigned South America type B clade (45 isolates), North
      America type 1 and Asia clade (2 isolates each one). H. capsulatum strains
      isolated from soil and from patients living in Argentina (45 of 49) clustered
      together with the H. capsulatum isolates of the South America B clade. The high
      level of genetic similarity among our isolates suggests that almost one genetic
      population is present in the microenvironment. Isolates described as H.
      capsulatum var. capsulatum or var. farciminosum (2 isolates) did not form a
      monophyletic group and were found in the Asia clade. Subsequent studies are
      needed to properly identify these isolates. 

PMID- 24299461
TI  - High-pressure synthesis, crystal structure, and properties of In2NiMnO6 with
      antiferromagnetic order and field-induced phase transition.
AB  - In2NiMnO6, a new compound extending the family of double rare-earth perovskites
      R2NiMnO6 (R = rare earth, Y) to smaller R ions, was prepared using a high
      pressure and high-temperature technique (6 GPa and 1600 K). Its crystal structure
      was investigated by synchrotron X-ray powder diffraction at room temperature:
      space group P2(1)/n (No. 14, cell choice 2), Z = 2, a = 5.13520(1) A, b =
      5.33728(1) A, c = 7.54559(4) A, and beta = 90.1343(1) degrees . A significant
      degree of ordering of Mn(4+) and Ni(2+) ions was observed. The dc and ac
      magnetization and specific heat measurements showed that In2NiMnO6 is an
      antiferromagnet with a Neel temperature TN of 26 K. Its antiferromagnetism puts
      it apart from other members of the R2NiMnO6 family where a ferromagnetic ground
      state was observed, which is attributed to the superexchange interaction between
      Mn(4+) and Ni(2+) ions according to the Kanamori-Goodenough rules. A field
      induced phase transition to a ferromagnetic state was observed from 18 kOe at 5
      K, indicating that In2NiMnO6 is close to the antiferromagnetic-ferromagnetic
      transition boundary. First-principles calculations allowed us to explain its
      antiferromagnetism and the field-induced phase transition and predict the E* type
      antiferromagnetic ground state.

PMID- 24299462
TI  - Renal dysfunction, restrictive left ventricular filling pattern and mortality
      risk in patients admitted with heart failure: a 7-year follow-up study.
AB  - BACKGROUND: Renal dysfunction is associated with a variety of cardiac alterations
      including left ventricular (LV) hypertrophy, LV dilation, and reduction in
      systolic and diastolic function. It is common and associated with an increased
      mortality risk in heart failure (HF) patients. This study was designed to
      evaluate whether severe diastolic dysfunction contribute to the increased
      mortality risk observed in HF patients with renal dysfunction. METHODS: Using Cox
      Proportional Hazard Models on data (N = 669) from the EchoCardiography and Heart
      Outcome Study (ECHOS) study we evaluated whether estimated glomerular filtration
      rate (eGFR) was associated with mortality risk before and after adjustment for
      severe diastolic dysfunction. Severe diastolic dysfunction was defined by a
      restrictive left ventricular filling pattern (RF) (=deceleration time < 140 ms)
      by Doppler echocardiography. RESULTS: Median eGFR was 58 ml/min/1.73 m2, left
      ventricular ejection fraction was 33% and RF was observed in 48%. During the 7
      year follow up period 432 patients died. Multivariable adjusted eGFR was
      associated with similar mortality risk before (Hazard Ratio(HR)(eGFR 10 ml
      increase): 0.94 (95% CI: 0.89-0.99, P = 0.024) and after (HR(eGFR 10 ml
      increase): 0.93 (0.89-0.99), P = 0.012) adjustment for RF (HR: 1.57 (1.28-1.93),
      P < 0.001). CONCLUSIONS: In patients admitted with HF RF does not contribute to
      the increased mortality risk observed in patients with a decreased eGFR. Factors
      other than severe diastolic dysfunction may explain the association between renal
      function and mortality risk in HF patients.

PMID- 24299463
TI  - Design, synthesis, and evaluation of hydroxamic acid derivatives as promising
      agents for the management of Chagas disease.
AB  - Today, there are approximately 8 million cases of Chagas disease in the southern
      cone of South America alone, and about 100 million people are living with the
      risk of becoming infected. The present pharmacotherapy is sometimes ineffective
      and has serious side effects. Here, we report a series of 4,5-dihydroisoxazoles
      incorporating hydroxamate moieties, which act as effective inhibitors of the
      carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g) was
      evaluated in detail and shows promising features as an antitrypanosomal agent.
      Excellent values for the inhibition of growth for all three developmental forms
      of the parasite were observed at low concentrations of 5g (IC50 values from 7.0
      to <1 MUM). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity
      to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream
      parasites and that all treated mice survived; it was also more effective than the
      standard drug benznidazole.

PMID- 24299464
TI  - Interaction of Rh with Rh nanoparticles encapsulated by ordered ultrathin
      TiO(1+x) film on TiO2(110) surface.
AB  - Rh films of 5-50 monolayers (ML) were grown on TiO2(110)-(1 * 1) surface by
      physical vapor deposition (PVD) at 300 K followed by annealing at max. 1050 K. In
      the coverage range of 5-15 ML, separated stripe-like Rh nanoparticles of
      approximately 30 * 150 nm lateral size and 10-20 layer thickness with a flat top
      (111) facet were formed. At higher coverages (15-50 ML), the Rh film sustained
      its continuity at least up to 950 K. For both cases, the Rh(111) top facets were
      completely covered by a long-range ordered hexagonal "wagon-wheel" TiO(1+x)
      ultrathin oxide (hw-TiO-UTO) film. STM-STS, XPS, LEIS, and TDS methods were used
      for morphologic and electronic characterization of surfaces prepared in this way.
      The main part of this study is devoted to the study of postdeposition of Rh on
      the hw-TiO-UTO layer at different temperatures (230 K, 310 K, 500 K) and to the
      effect of subsequent annealing. It was found that 2D nanoparticles of 0.2-0.3 nm
      height and 1-2 nm diameter are formed at RT and their average lateral size
      increases gradually in the range of 300-900 K. The LEIS intensity data and the CO
      TDS titration of the particles have shown that an exchange of the postdeposited
      Rh atoms with the hw-TiO-UTO layer proceeds to an extent of around 50% at 230 K
      and this value increases up to 80-90% in the range of 300-500 K. The total
      disappearance of the characteristic LEIS signal for Rh takes place at around 900
      K where a complete hw-TiO-UTO adlayer forms on top of the postdeposited metal
      (100% exchange).

PMID- 24299465
TI  - Evolution in fluctuating environments: decomposing selection into additive
      components of the Robertson-Price equation.
AB  - We analyze the stochastic components of the Robertson-Price equation for the
      evolution of quantitative characters that enables decomposition of the selection
      differential into components due to demographic and environmental stochasticity.
      We show how these two types of stochasticity affect the evolution of multivariate
      quantitative characters by defining demographic and environmental variances as
      components of individual fitness. The exact covariance formula for selection is
      decomposed into three components, the deterministic mean value, as well as
      stochastic demographic and environmental components. We show that demographic and
      environmental stochasticity generate random genetic drift and fluctuating
      selection, respectively. This provides a common theoretical framework for linking
      ecological and evolutionary processes. Demographic stochasticity can cause random
      variation in selection differentials independent of fluctuating selection caused
      by environmental variation. We use this model of selection to illustrate that the
      effect on the expected selection differential of random variation in individual
      fitness is dependent on population size, and that the strength of fluctuating
      selection is affected by how environmental variation affects the covariance in
      Malthusian fitness between individuals with different phenotypes. Thus, our
      approach enables us to partition out the effects of fluctuating selection from
      the effects of selection due to random variation in individual fitness caused by
      demographic stochasticity. 

PMID- 24299466
TI  - Discontinuation of clozapine: a 15-year naturalistic retrospective study of 320
      patients.
AB  - OBJECTIVE: Clozapine is underutilized in the management of treatment-resistant
      schizophrenia. To understand contributing factors, we analyzed the frequency and
      causes of clozapine discontinuations that occurred over a 15-year period in a
      clinical setting. METHOD: Data were extracted from computerized records and from
      mandatory termination reports for discontinuation events 1993-2007. The reasons
      for termination were analyzed. RESULTS: Over half of the patients (n = 183/320;
      57%) had at least one discontinuation (median time 609 days). The two most common
      causes for discontinuation were non-adherence (35%) and side-effects (28%).
      Hematological side-effects accounted for 45% of all side-effect associated
      discontinuations; most such patients remained eligible for clozapine treatment,
      and a significant fraction remained on clozapine after rechallenge. Central
      nervous system side-effects accounted for 35% of side-effect induced
      discontinuations. General factors significantly associated with discontinuation
      were African American race, older age at initiation of clozapine and less
      improvement in psychiatric symptoms. CONCLUSION: In addition to anticipating and
      addressing causes of non-adherence, psychiatrists should consider clozapine
      rechallenge in eligible patients and implement measures to mitigate clozapine
      associated sedation, seizures, and other side-effects. Future studies should
      particularly address why African American and older patients may be more likely
      to discontinue clozapine.

PMID- 24299467
TI  - Antibiotic exposure in the first two years of life and development of asthma and
      other allergic diseases by 7.5 yr: a dose-dependent relationship.
AB  - BACKGROUND: Antibiotic use in infancy disrupts gut microflora during a critical
      period for immune system development. It is hypothesized that this could
      predispose to the development of allergic diseases. We investigated the
      associations of antibiotic use in the first 2 yr of life with the development of
      asthma, eczema or hay fever by age 7.5 yr in a longitudinal birth cohort.
      METHODS: Subjects were 4952 children from the Avon Longitudinal Study of Parents
      and Children (ALSPAC). Child antibiotic use and asthma, eczema and hay fever
      symptoms were maternally reported. Atopy was assessed by skin prick tests at age
      7.5 yr. The total number of antibiotic courses was considered as the main
      exposure. Data were analysed using multivariate logistic regression. RESULTS:
      Children reported to have taken antibiotics during infancy (0-2 yr) were more
      likely to have asthma at 7.5 yr (OR 1.75, 95% CI 1.40-2.17), and the odds (OR,
      [95% CI]) increased with greater numbers of courses: once 1.11 [0.84-1.48]; twice
      1.50 [1.14-1.98]; three times 1.79 [1.34-2.40]; four times or more 2.82 [2.19
      3.63]. Increased antibiotic use was also associated with higher odds of eczema
      and hay fever but not atopy. The effect appeared to be associated with cumulative
      rather than a critical period of exposure during the first 2 yr. CONCLUSIONS: A
      robust and dose-dependent association was found between antibiotic use in the
      first 2 yr of life and asthma at age 7.5 yr but did not appear to be mediated
      through an association with atopy.

PMID- 24299468
TI  - Human skin cell fractions fail to self-organize within a gellan gum/hyaluronic
      acid matrix but positively influence early wound healing.
AB  - Split-thickness autografts still are the current gold standard to treat skin,
      upon severe injuries. Nonetheless, autografts are dependent on donor site
      availability and often associated to poor quality neoskin. The generation of
      dermal-epidermal substitutes by tissue engineering is seen as a promising
      strategy to overcome this problematic. However, solutions that can be safely and
      conveniently transplanted in one single surgical intervention are still very
      challenging as their production normally requires long culture time, and graft
      survival is many times compromised by delayed vascularization upon
      transplantation. This work intended to propose a strategy that circumvents the
      prolonged and laborious preparation period of skin substitutes and allows skin
      cells self-organization toward improved healing. Human dermal/epidermal cell
      fractions were entrapped directly from isolation within a gellan gum/hyaluronic
      acid (GG-HA) spongy-like hydrogel formed from an off-the-shelf dried polymeric
      network. Upon transplantation into full-thickness mice wounds, the proposed
      constructs accelerated the wound closure rate and re-epithelialization, as well
      as tissue neovascularization. A synergistic effect of the GG-HA matrix and the
      transplanted cells over those processes was demonstrated at early time points.
      Despite the human-derived and chimeric blood vessels found, the proposed matrix
      did not succeed in prolonging cells residence time and in sustaining the self
      organization of transplanted human cells possibly due to primitive degradation.
      Despite this, the herein proposed approach open the opportunity to tackle wound
      healing at early stages contributing to re-epithelialization and
      neovascularization. 

PMID- 24299469
TI  - A pilot study analyzing the effects of Chinese cupping as an adjunct treatment
      for patients with subacute low back pain on relieving pain, improving range of
      motion, and improving function.
AB  - BACKGROUND: Cupping, a classic Chinese medicine treatment, is a technique that
      applies suction cups over soft tissue. Cupping is gaining popularity in physical
      medicine because of the simplicity in application, minimal adverse effects, and
      reduction in pain and muscle tenderness. These factors also make it a cost
      effective intervention. For this study, cupping was used to treat low back pain
      (LBP). OBJECTIVE: To evaluate the effectiveness of Chinese cupping in acutely
      reducing pain, decreasing tenderness to palpation, and improving range of motion
      for patients with subacute or chronic LBP. PATIENTS/SETTING: Twenty-one patients
      who reported back pain for at least 8 weeks volunteered at a multidisciplinary
      holistic outpatient clinic. INTERVENTION: After completion of a medical screening
      questionnaire and collection of baseline data, 4 glass cups were applied and
      pressurized over the lower erector spinae muscles. OUTCOME MEASUREMENTS: Baseline
      data included demographic characteristics and the Oswestry Disability
      Questionnaire score. Pre- and postintervention data included perceived pain on a
      visual analog scale (VAS), lumbar spine range of motion, straight-leg raise test
      (SLR), and pain-pressure threshold (PPT) assessed with a digital force gauge. The
      data were analyzed by using a Wilcoxon signed-rank test and Spearman rho
      correlations. RESULTS: Of the 17 patients who completed the study, there were
      significant post-treatment improvements in VAS scores (p=0.0001), SLR motion on
      the left (p=0.043), and lumbar flexion range of motion (p=0.016) and improvements
      in PPT at all 4 investigated points (p<0.007). Significant relationships were
      identified between the improvement in low back flexion with the improvement in
      PPT at bilateral lumbar paraspinal muscles at the L4 levels and at the left L2
      level. CONCLUSIONS: Chinese cupping may be a low-risk, therapeutic treatment for
      the prompt reduction of symptoms associated with subacute and chronic low back
      pain. Cupping may allow patients to progress to functional movement training in a
      timely manner by promptly reducing pain and muscle tenderness and improving range
      of motion.

PMID- 24299470
TI  - The role of endovascular treatment for ruptured distal anterior cerebral artery
      aneurysms: comparison with microsurgical clipping.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare clinical
      outcomes and treatment-related complications between coiling and clipping for
      ruptured distal anterior cerebral artery (DACA) aneurysms. METHODS: Eighty-four
      consecutive patients (M:F = 36:48; mean 53.8 years) with ruptured DACA aneurysms
      were treated by either clipping (n = 46, 54.8%) or coiling (n = 38, 45.2%). The
      clinical outcomes and procedure-related complications were evaluated and compared
      between the two groups. RESULTS: Procedure-related complications tend to occur
      more frequently in the clipping (n = 6, 13.0%) than coiling group (n = 1, 2.6%)
      (P = .121). At discharge, 51 patients (60.7%) had favorable outcomes (Glasgow
      outcome scale [GOS], 4 or 5). There was no significant difference between the two
      groups in favorable outcome (63.2% vs. 58.7%; P = .677). Hunt and Hess (HH) grade
      (P < .001; 95% CI, 3.354-29.609) and treatment modality (P = .044; 95% CI, 1.039
      16.325) were independent risk factors for poor outcome (GOS, 1-3). CONCLUSIONS:
      Coiling was more favorable to clipping in clinical outcomes and incidence of
      treatment-related complications for ruptured DACA aneurysms.

PMID- 24299471
TI  - Identification of immunogenic proteins of Candida parapsilosis by serological
      proteome analysis.
AB  - AIMS: Systemic candidiasis is the leading fungal bloodstream infection, and its
      incidence has been on the rise. Recently, Candida parapsilosis has emerged as an
      increasingly prevalent fungal pathogen, but little is known about its antigenic
      profile. Hence, the current work was performed to discover immunogenic proteins
      of C. parapsilosis using serological proteome analysis. METHODS AND RESULTS: Cell
      wall proteins extracted from C. parapsilosis were resolved by two-dimensional
      electrophoresis followed by immunoblotting using antisera from experimentally
      infected mice. Mass spectrometry analysis of the 32 immunoreactive protein spots
      resulted in the identification of 12 distinct proteins. Among them, 11 proteins
      were known antigens of Candida albicans, whereas Idh2p was identified for the
      first time as an immunogenic protein of Candida species. Recombinant Idh2p was
      expressed in Escherichia coli, and its antigenicity was verified by immunoblot
      analysis. CONCLUSIONS: An immunoproteomic approach was successfully applied to
      identify immunogenic proteins of C. parapsilosis, with Idh2p as a novel candidate
      antigen. The identified antigens may serve as potential biomarkers for
      development of diagnostic assay and/or vaccine for C. parapsilosis. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This work represents the first immunoproteomic analysis
      of C. parapsilosis, which provides new insights into host-pathogen interactions
      and pathogenesis of C. parapsilosis. The immunogenic proteins could be studied as
      biomarker candidates for C. parapsilosis.

PMID- 24299472
TI  - Does hemodiafiltration reduce vascular stiffness measured by aortic pulse wave
      velocity compared with high-flux hemodialysis?
AB  - Hemodialfiltration (HDF) has been reported to reduce the frequency of
      intradialytic hypotension compared with hemodialysis (HD). We wished to determine
      whether HDF resulted in improvement of arterial stiffness compared with HD. We
      reviewed peripheral blood pressure and pulse wave velocity measurements in a
      cross-sectional analysis of stable HDF and HD outpatients. One hundred forty-one
      HDF patients were matched to 148 HD patients in terms of age, sex, prevalence of
      diabetes, peripheral blood pressure, and body mass. Pulse wave velocity was not
      different between the HD and HDF cohorts (median 9.1 [8.0-10.7] m/s vs. 9.7 [8.5
      11.6] m/s). Similarly, there were no differences in central aortic pressure
      (149.2 +/- 30.9 mmHg vs. 151.9 +/- 35.2 mmHg), or aortic (39 [25.1-51.2]% vs.
      38.6 [25.8-51.4]%) and brachial (3.8 [-24.3 to 26.9]% vs. 3 [-22.4 to 27.1]%)
      augmentation indices, respectively. Pulse wave velocity did not differ between
      adult patients treated by HD and HDF, and similarly, there were no differences in
      central aortic pressure, aortic or brachial augmentation indices, and cardiac
      diastolic perfusion. Our study suggests that HDF does not appear to offer any
      benefit over HD in terms of vascular stiffness.

PMID- 24299473
TI  - Evans syndrome associated with sterile inflammation of the central nervous
      system: a case report.
AB  - INTRODUCTION: Evans syndrome is a rare hematological disease commonly defined as
      Coombs-positive hemolytic anemia and immune thrombocytopenia. Pathophysiology of
      this disease involves decreased cluster of differentiation (CD)4+ T-helper cell
      counts, increased CD8+ T-suppressor cell counts, a decreased CD4/CD8 ratio, and
      reduced serum immunoglobulin G, M and A levels - indicating a complex immune
      dysregulation. Association with other autoimmune diseases has been described
      although involvement of the central nervous system has not been reported so far.
      CASE PRESENTATION: We here present a case of a 28-year-old woman of Turkish
      origin with progressive, disseminated, partly mass-forming lymphoplasmacellular
      infiltration (CD3+ and CD138+ cells) of the brain in association with Evans
      syndrome. No other central nervous system disorder could be identified on
      neuropathological evaluation. Although treatment with rituximab was effective to
      normalize erythrocyte and thrombocyte levels in her peripheral blood, it failed
      to dampen the inflammation in her central nervous system or prevent clinical
      progression. Initiation of treatment with cyclophosphamide resulted in
      stabilization of her central nervous system inflammation and the disease course.
      CONCLUSIONS: The complex immune dysregulation resulting in the antibody-mediated
      pathologies that can be regarded as the cause of both lymphoplasmacellular
      encephalitis and Evans syndrome renders this association to be of clinical
      relevance for both neurologists and hematologists. Our experience also sheds
      light on the effectiveness of different treatments for both disorders and we
      advise clinicians to take a closer look when encountering a combination of
      peripheral blood diseases with affection of the central nervous system.

PMID- 24299474
TI  - The use of archived tags in retrospective genetic analysis of fish.
AB  - Collections of historical tissue samples from fish (e.g. scales and otoliths)
      stored in museums and fisheries institutions are precious sources of DNA for
      conducting retrospective genetic analysis. However, in some cases, only external
      tags used for documentation of spatial dynamics of fish populations have been
      preserved. Here, we test the usefulness of fish tags as a source of DNA for
      genetic analysis. We extract DNA from historical tags from cod collected in
      Greenlandic waters between 1950 and 1968. We show that the quantity and quality
      of DNA recovered from tags is comparable to DNA from archived otoliths from the
      same individuals. Surprisingly, levels of cross-contamination do not seem to be
      significantly higher in DNA from external (tag) than internal (otolith) sources.
      Our study therefore demonstrates that historical tags can be a highly valuable
      source of DNA for retrospective genetic analysis of fish. 

PMID- 24299475
TI  - How peculiar: the case of a rare tumour.

PMID- 24299476
TI  - Foundations of the research foundation.

PMID- 24299477
TI  - Development of clinical guidelines for the prescription of a seated wheelchair or
      mobility scooter for people with traumatic brain injury or spinal cord injury.
AB  - BACKGROUND/AIM: Providing a wheelchair or scooter is a complex therapy
      intervention aimed at enhancing the person's functioning. The research and
      experience has shown that a wheelchair which is poorly matched to the individual,
      adversely affects potential activities and participation, lifestyle goals, health
      status and can be costly. The development of an evidence-based clinical guideline
      will provide a synthesis of the evidence and recommendations for best practice.
      METHODS: The guidelines were developed using a rigorous methodology of systematic
      search for primary studies, critical appraisal and synthesis of the evidence
      using an adaptation of the National Health and Medical Research Council
      recommendation grades in conjunction with a multidisciplinary working party.
      RESULTS: Seventy-six recommendations were developed from 44 clinical questions
      related to goals, assessment and review, capacity and performance, upper limb
      capacity and injury risk, wheelchair features, propulsion, training, transport
      and maintenance. Resources were developed to support the use of the guidelines.
      Only examples of recommendations are provided here. The complete guidelines and
      technical report should be downloaded from
      http://www.lifetimecare.nsw.gov.au/Brain_Injury.aspx. CONCLUSION: The guidelines
      provide appraisal and synthesis of the literature and recommendations for best
      practice on the prescription of a wheelchair or scooter for adults with spinal
      cord injury and/or traumatic brain injury. The guidelines are intended to reduce
      the potential for poor wheelchair prescription, inform and guide practice to
      enhance outcomes. Through judicious application of the available research, these
      guidelines provide best practice recommendations for prescribing the most
      appropriate wheelchair for a person with a traumatic brain injury/spinal cord
      injury.

PMID- 24299478
TI  - Enhancing retention of occupational therapists working in mental health:
      relationships between wellbeing at work and turnover intention.
AB  - BACKGROUND/AIM: Occupational therapists working in mental health who experience
      burnout, low work engagement or poor job satisfaction are at risk of poor
      wellbeing at work and may be more likely to leave their jobs. The aim of this
      project was to explore factors associated with wellbeing at work and turnover
      intention in a sample of occupational therapists working in mental health.
      METHODS: One hundred and three occupational therapists working in mental health
      in Queensland completed a survey exploring work/life balance, effort invested in
      work, rewards received from work, wellbeing at work (job satisfaction, burnout
      and work engagement) and turnover intention. Analyses were conducted to explore
      relationships between work/life balance, effort, reward, wellbeing at work and
      turnover intention. RESULTS: All measures of wellbeing at work were significantly
      associated with turnover intention. A large proportion (33%) of the variance in
      turnover intention was predicted by job satisfaction. Perceptions of both
      work/life balance and effort invested in work, as well as perceived rewards in
      terms of recognition, prestige and personal satisfaction were significantly
      associated with work-related wellbeing scores. CONCLUSIONS AND SIGNIFICANCE OF
      THE STUDY: Results from this study deepen the understanding of factors associated
      with wellbeing at work and turnover intention for occupational therapists in
      mental health. This knowledge will support the development of interventions aimed
      at reducing turnover intention and enhancing retention of occupational therapists
      in the mental health workforce.

PMID- 24299479
TI  - Pre-surgery education for elective cardiac surgery patients: a survey from the
      patient's perspective.
AB  - BACKGROUND/AIM: Multidisciplinary pre-admission patient education is commonly
      recommended for elective surgery patients, and may involve the provision of
      written information and presentations from the health team. However, the
      occupational therapy role with elective sternotomy patients in our setting is
      confined to the post-operative period. We aimed to evaluate cardiac surgery
      patients' perception of the effectiveness and timing of pre-admission
      multidisciplinary written information and post-operative verbal education
      provided by occupational therapy. METHODS: This cross-sectional study involved a
      written survey, which was posted to 375 people who had undergone cardiac surgery
      in 2009-2010. Questions were designed to elicit patient perceptions of both pre
      operative written information and post-operative education relating to post
      operative precautions and return to activity received from occupational therapy.
      RESULTS: There were 118 surveys returned equalling a 31.4% response rate. Eighty
      nine per cent of respondents recalled receiving and reading the pre-surgery
      information booklet, and this was significantly correlated with feeling prepared
      for the post-operative experience and adherence with precautions (P < 0.0001).
      Exactly 30.4% of respondents stated that they experienced stress and anxiety in
      relation to post-operative expectations, and 47.3% felt the information provided
      in the occupational therapy education sessions would have been more beneficial
      for their understanding and coping if provided prior to surgery. CONCLUSIONS:
      Multidisciplinary written pre-surgery education appears to be providing patients
      with a good understanding of what to expect following surgery. The results
      suggest that pre-operative verbal education from occupational therapy would
      assist in reducing anxiety in a subgroup of patients.

PMID- 24299480
TI  - Complementary contribution of parents and therapists in the assessment process of
      children.
AB  - BACKGROUND/AIM: Traditional developmental models assume that the underlying
      capacities of children contribute to their participation. In this framework,
      preschoolers who are referred for occupational therapy services usually undergo
      an assessment intended to identify capacities in certain domains. Contrary to
      this, newer ecological models assume that child participation is a consequence of
      a multidimensional interaction between personal and environmental factors. As a
      result clinicians are increasingly focusing their assessment on performance and
      participation. This study aimed to assess the correlation between children's
      performance skills, their capacities and participation; and to explore whether
      parents' observations, alongside therapist observations and standardised
      assessments, contribute to an enhanced understanding of child participation.
      METHOD: Participants included 188 parents and their children, aged 4-6 years,
      with and without mild developmental difficulties. Data were collected using
      standardised assessments for child capacities, and questionnaires completed by
      parents and occupational therapists regarding child participation and performance
      skills. RESULTS: Significant correlations were found between parent assessments
      of child performance skills and child participation, but not with child
      capacities. The opposite was found to be true for occupational therapist
      assessments of child performance skills which were found to correlate with child
      capacities, but not with participation. Additionally, an interaction effect was
      found for both groups. Occupational therapists reported higher performance skills
      as compared to parents, but the difference was only significant for children
      without mild difficulties. CONCLUSION: As suggested by ecological models of child
      participation, the findings highlight the importance of parent-therapist
      collaboration in the assessment process of children.

PMID- 24299481
TI  - Older male mentors' perceptions of a Men's Shed intergenerational mentoring
      program.
AB  - BACKGROUND/AIM: The National Male Health Policy identifies several groups of
      males at different transitional life stages that are at particular risk,
      including teenage boys at risk of social exclusion and recently retired older
      men. A novel intergenerational mentoring program was developed to bring these
      groups together through participation in meaningful occupation. This research
      aimed to investigate the mentors' experiences of the program, their views about
      the teenage boys and the structure of the program. METHODS: Nine teenage boys (14
      16 years) at risk of social exclusion participated in a weekly shared
      construction project with older male mentors (60-75 years) at a local Sydney
      school over one school term. A post-project focus group and individual interviews
      were conducted with six of the mentors pre- and post-project. Data were analysed
      using the constant comparative method of grounded theory; all authors developed
      themes individually and then collectively. RESULTS: The core theme that emerged
      was a values-led male reconnection. Centred in themes of gendered valuing,
      respect, tradition and the handing down of life experience, occupational
      engagement was integral to bridging the generational gap and facilitating
      intergeneration discourse. CONCLUSION: Older males with a strong sense of
      generativity are a valuable resource in delivering such programs, and reported a
      sense of accomplishment and enhanced self-worth. Given the central role that
      occupational engagement played in fusing the project, this study highlights the
      untapped role of occupational therapy in developing programs aimed at promoting
      the health and wellbeing of Australian men.

PMID- 24299482
TI  - Learning experiences on role-emerging placements: an exploration from the
      students' perspective.
AB  - BACKGROUND/AIM: Occupational therapy educators are challenged to provide students
      with practical experiences which prepare them for ever changing health-care
      contexts on graduation. Role-emerging placements have been widely used
      internationally to help meet this challenge, but research into the learning
      experiences of students during these innovative placements is limited. This
      research investigated the enablers and barriers to learning from the perspectives
      of students on such placements from two European universities. METHODS: Two
      separate qualitative studies tracked 10 final year students. Interviews explored
      their learning experiences prior to, during and after an eight- or 10-week role
      emerging placement in a range of settings. RESULTS: Four themes emerged, which
      were (1) adapting to less doing, more thinking and planning; (2) understanding
      the complexity of collaboration and making it work; (3) emotional extremes; and
      (4) realising and using the occupational therapy perspective. CONCLUSIONS: These
      placements presented a 'roller coaster' of authentic learning experiences which
      created the opportunity for students to use occupation in practice and develop
      skills for collaborative working in an interprofessional environment. Whereas
      students viewed their role-emerging placement experiences positively, challenges
      included the emotional responses of students and placement pace. Findings suggest
      the need for supportive student placement experiences in both established and
      role-emerging areas to prepare students for a range of opportunities in an
      uncertain future.

PMID- 24299483
TI  - Expectations of parents on low incomes and therapists who work with parents on
      low incomes of the first therapy session.
AB  - BACKGROUND/AIM: Family-centred practice involves allowing families' needs to
      direct therapy. Parents and therapists often come from different socio-economic
      positions, yet little is known about how this impacts family-centred practice.
      This study aimed to explore expectations of care among parents on low incomes and
      among occupational therapists who work with these families. METHOD: Ten parents
      who were holders of a low-income Health Care Card and had a child on a waiting
      list for publicly funded occupational therapy services, and nine paediatric
      occupational therapists were asked about perceptions of therapy using semi
      structured, in-depth interviews. Interview transcripts were analysed using a
      qualitative descriptive approach. RESULTS: While therapists recognised families'
      expectations that therapy would 'fix' their child, some of the concerns of
      parents such as how their child's behaviour reflected on their parenting skills
      went largely unrecognised. In addition, no therapists recognised parents' primary
      concerns about their child's physical health, their desires for a structured
      approach to therapy or the somewhat fatalistic approach some parents were taking
      to therapy. Some therapists recognised the complexities they encountered in
      engaging with parents from low socio-economic positions and tried to adapt their
      practice with some taking less of a family-centred approach and focussing on the
      needs of either the parent or the child while others continued to practice with a
      focus on the family as a whole. CONCLUSION: These findings have implications for
      therapists seeking to work within a framework of family-centred practice with
      clients from low socio-economic positions.

PMID- 24299484
TI  - Relocating to retirement living: an occupational perspective on successful
      transitions.
AB  - BACKGROUND/AIM: Older adults are increasingly relocating to alternative housing
      options, such as retirement villages. Relocations can be stressful and these
      environmental transitions can cause significant disruption to the person
      environment and occupational fit, thus influencing health, well-being and quality
      of life. There is a lack of literature from an occupational therapy perspective
      in relation to healthy older adults seeking to relocate. This study aimed to
      identify issues healthy older adults face when relocating to retirement living,
      what strategies they used during this process, how they maintained a sense of
      home, and the potential for occupational therapy involvement. METHODS: Sixteen
      semi-structured, in-depth interviews were conducted with participants recruited
      from retirement living facilities across three stages of relocation; 'Decision',
      'Early Days', and 'Established'. A grounded theory approach was used to code and
      analyse the data. RESULTS: Having control over the decisions surrounding
      relocation, being proactive rather than reactive and preparing sufficiently for
      the move all contributed to a positive post-location adjustment. Four main themes
      emerged from the narratives: timing of decision making, new beginnings,
      continuity, and strategies for change. CONCLUSIONS: This study contributes to
      literature surrounding how older adults occupy and make meaning of the spaces
      they call home and also enriches literature regarding environmental transitions.
      Relocation can be a disruptive process and occupational therapists are uniquely
      placed to facilitate healthy ageing throughout this transition using preventative
      and community-based occupational therapy.

PMID- 24299485
TI  - Competent use of a motorised mobility scooter--assessment, training and ongoing
      monitoring: a vital role for occupational therapy practice.

PMID- 24299486
TI  - Re: the dark side of occupation: a concept for consideration.

PMID- 24299487
TI  - Response to re: the dark side of occupation: a concept for consideration.

PMID- 24299489
TI  - The relative effect of sterols and hopanoids on lipid bilayers: when comparable
      is not identical.
AB  - Sterols are the hallmarks of eukaryotic membranes where they are often found in
      specialized functional microdomains of the plasma membrane called lipid rafts.
      Despite some notable exceptions, prokaryotes lack sterols. However, growing
      evidence has suggested the existence of raft-like domains in the plasma membrane
      of bacteria. A structurally related family of triterpenoids found in some
      bacteria called hopanoids has long been assumed to be bacterial surrogates for
      sterols in membranes. Although the effect of sterols, in particular cholesterol,
      on lipid bilayers has been extensively characterized through experimental and
      simulation studies, those of hopanoids have hardly been investigated. In this
      study, molecular dynamics simulations are used to examine the effect of two
      hopanoids, diploptene (hop-22(29)-ene) and bacteriohopanetetrol ((32R,33S,34S)
      bacteriohopane-32,33,34,35-tetrol), on a model bilayer. The results are compared
      with those obtained for cholesterol and a pure phosphatidylcholine bilayer. It is
      shown that diploptene and bacteriohopanetetrol behave very differently under the
      conditions simulated. Whereas bacteriohopanetetrol adopted a cholesterol-like
      upright orientation in the bilayer, diploptene partitioned between the two
      leaflets inside the bilayer. Analysis of various structural properties (area per
      lipid, electron density profile, tilt angle of the lipids, and conformation and
      order parameters of the phosphatidylcholine tails) in bacteriohopanetetrol- and
      cholesterol-containing bilayers indicates that the condensing and ordering effect
      of bacteriohopanetetrol is weaker than that of cholesterol. The simulations
      suggest that the chemical diversity of hopanoids may lead to a broader range of
      functional roles in bacterial membranes than sterols in eukaryotic membranes. 

PMID- 24299491
TI  - Knockdown of Sec8 promotes cell-cycle arrest at G1/S phase by inducing p21 via
      control of FOXO proteins.
AB  - p21(Cip1) protein inhibits the activity of cyclins at the G(1) checkpoint and
      influences transition of cells from the G(1) to the S phase of the cell cycle.
      Moreover, expression of members of the FOXO family (active form of forkhead
      transcription factors of the O class) in dividing cells promotes cell-cycle
      arrest at the G(1)/S boundary via regulation of p21(Cip1). Recently, the exocyst
      complex, including Sec8, has been implicated in various roles independent of its
      role in secretion, such as cell migration, invadopodia formation, cytokinesis,
      glucose uptake and neural development. Given the essential roles of the exocyst
      complex in cellular and developmental processes, disruption of its function may
      be involved in various diseases such as cancer, diabetes and neuronal disorders.
      However, the relationship between Sec8 and the cell cycle remains to be
      elucidated. In this study, knockdown of Sec8 inhibited cell growth and promoted
      cell-cycle arrest at the G(1)/S phase by control of p21 expression and
      retinoblastoma protein phosphorylation. Furthermore, Sec8 regulated FOXO family
      proteins via ubiquitin-proteasome degradation by regulating the expression of the
      murine double minute 2 (Mdm2) protein but not S-phase kinase-associated protein 2
      (Skp2).

PMID- 24299492
TI  - Response to neoadjuvant treatment of invasive ductal breast carcinomas including
      outcome evaluation: MRI analysis by an automatic CAD system in comparison to
      visual evaluation.
AB  - BACKGROUND: The aim of this study was to evaluate imaging-based response to
      standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced
      magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an
      automatic computer-assisted diagnosis (CAD) system in comparison to visual
      evaluation. MRI findings were correlated with histopathologic response to NACT
      and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND
      METHODS: Fifty-four patients with invasive ductal breast carcinomas received two
      identical MRI examinations (before and after NACT; 1.5T, contrast medium
      gadoteric acid). Pre-therapeutic images were compared with post-therapeutic
      examinations by CAD and two blinded human observers, considering morphologic and
      dynamic MRI parameters as well as tumor size measurements. Imaging-assessed
      response to NACT was compared with histopathologically verified response. All
      clinical, histopathologic, and DCE-MRM parameters were correlated with the
      occurrence of distant metastases. RESULTS: Initial and post-initial dynamic
      parameters significantly changed between pre- and post-therapeutic DCE-MRM.
      Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%,
      and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to
      histopathology. CAD analysis led to more false-negative findings (37.0%) compared
      to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of
      100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters
      showed significant associations to occurring metastases: Post-initial curve type
      before NACT (entire lesions, calculated by CAD) and post-initial curve type of
      the most enhancing tumor parts after NACT (calculated by CAD and manually).
      CONCLUSIONS: In the accurate evaluation of response to neoadjuvant treatment, CAD
      systems can provide useful additional information due to the high specificity;
      however, they cannot replace visual imaging evaluation. Besides traditional
      prognostic factors, contrast medium-induced dynamic MRI parameters reveal
      significant associations to patient outcome, i.e. occurrence of distant
      metastases.

PMID- 24299490
TI  - N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by
      inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain.
AB  - AIMS: This study explores the neuroprotective effects and mechanisms of N-acetyl
      L-cysteine (NAC) in mice exposed to cadmium (Cd). METHODS: NAC (150 mg/kg) was
      intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking
      water for 6 weeks. The changes of cell damage and death, reactive oxygen species
      (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR)
      signalling pathway in brain neurones were assessed. To verify the role of mTOR
      activation in Cd-induced neurotoxicity, mice also received a subacute regimen of
      intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg)
      for 11 days. RESULTS: Chronic exposure of mice to Cd induced brain damage or
      neuronal cell death, due to ROS induction. Co-administration of NAC significantly
      reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd
      induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell
      death. The protective effect of NAC was mediated, at least partially, by
      elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione
      peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd
      induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC.
      Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity.
      CONCLUSIONS: NAC protects against Cd-induced neuronal apoptosis in mouse brain
      partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The
      findings highlight that NAC may be exploited for prevention and treatment of Cd
      induced neurodegenerative diseases.

PMID- 24299493
TI  - Splitting molecular oxygen en route to a stable molecule containing diphosphorus
      tetroxide.
AB  - In contrast to stable phosphorus oxides such as P4O6 and P4O10 that possess
      iconic adamantane-like cage structures, highly reactive phosphorus oxides such as
      PO, PO2, and P2Ox (x = 1-5) only have been studied in the gas phase or by matrix
      isolation techniques. Elusive diphosphorus tetroxide, the long sought phosphorus
      analogue of N2O4, is particularly noteworthy. Computations predict that the oxo
      bridged O2POPO form of P2O4 is energetically more favored than the P-P bonded O2P
      PO2 isomer. Herein, we report the experimental realization of diphosphorus
      tetroxide-in its energetically disfavored O2P-PO2 form-via carbene-stabilization.
      The synthesis of the title compound involves the splitting of molecular oxygen by
      carbene-stabilized diphosphorus. 

PMID- 24299494
TI  - Using synthetic biological parts and microbioreactors to explore the protein
      expression characteristics of Escherichia coli.
AB  - Synthetic biology has developed numerous parts for the precise control of protein
      expression. However, relatively little is known about the burden these place on a
      host, or their reliability under varying environmental conditions. To address
      this, we made use of synthetic transcriptional and translational elements to
      create a combinatorial library of constructs that modulated expression strength
      of a green fluorescent protein. Combining this library with a microbioreactor
      platform, we were able to perform a detailed large-scale assessment of transient
      expression and growth characteristics of two Escherichia coli strains across
      several temperatures. This revealed significant differences in the robustness of
      both strains to differing types of protein expression, and a complex response of
      transcriptional and translational elements to differing temperatures. This study
      supports the development of reliable synthetic biological systems capable of
      working across different hosts and environmental contexts. Plasmids developed
      during this work have been made publicly available to act as a reference set for
      future research. 

PMID- 24299495
TI  - Development and evaluation of a dry powder formulation of liposome-encapsulated
      oseltamivir phosphate for inhalation.
AB  - This study aims to develop oseltamivir phosphate (OP) liposomes as inhalation
      powders by spray-drying based on the single factor investigation, which was
      mainly composed of lactose, L-leucine and mannitol. It was found that the ratio
      of OP and liposomes (1:10), inlet temperature (110  degrees C) and airflow rate
      (2.3 mL/min) showed optimized physical properties of OP liposomes. Deposition was
      evaluated after the aerosolization of powders at 600 L/h via the Aerolizer(r)
      into a twin-stage impinger. The concentrations of OP and oseltamivir carboxylate
      (OSCA) in rats plasma using LC-MS have been determined and performed via
      pharmacokinetic software DAS 2.0 package. The liposomal OP dry powders displayed
      an average particle size around 3.5 um with fine particle fraction (FPF =
      35.40%). In vitro evaluation demonstrated a sustained release pattern accounting
      for 20% drug release compared to that of OP solution up to 90% drug release in 2
      h. And the cumulative release percentage was up to 50% in 20 h. Atrioventricular
      fitting results indicated that all preparations were best fitted with a two
      compartment model. There was a significant difference in MRT, Cmax and Tmax (p <
      0.01) between the two groups of liposomal OP dry powders and OP solution with t
      test, which indicated that the drug released slowly from liposomal OP dry powders
      in the lung. To sum up, dry powders formulation of liposome-encapsulated OP for
      inhalation was suitable for pulmonary administration, which offering the
      opportunity to reduce dosing frequency.

PMID- 24299496
TI  - Fluorescent organic nanoparticles of Biginelli-based molecules: recognition of
      Hg2+ and Cl- in an aqueous medium.
AB  - Biginelli-based molecules (1-3) have been synthesized and developed as a new
      class of fluorescent organic nanoparticle-based chemosensors. Chemosensor 2 has
      shown excellent selectivity and sensitivity for detection of Hg(2+) in an aqueous
      medium. It can detect Hg(2+) up to 1 nM, and the resultant 2Hg(2+) complex can
      detect Cl(-) ions (micromolar level) in an aqueous medium. 

PMID- 24299497
TI  - The ReSPonD trial--rivastigmine to stabilise gait in Parkinson's disease a phase
      II, randomised, double blind, placebo controlled trial to evaluate the effect of
      rivastigmine on gait in patients with Parkinson's disease who have fallen.
AB  - BACKGROUND: Gait impairment is common in people with Parkinson's disease. There
      is a lack of effective interventions to target this debilitating complication and
      therefore a need to identify new therapeutic options. An underlying cholinergic
      deficit contributes to both the gait and cognitive dysfunction seen in
      Parkinson's disease. The combined impact of both impairments can be assessed in
      gait tasks performed with concomitant cognitive tasks. The aim of this trial is
      to evaluate the impact of a cholinesterase inhibitor on cognitive function and
      gait performance in people with established Parkinson's disease. METHODS/DESIGN:
      This is a single centre, double-blind, randomised placebo-controlled trial in 130
      people with Hoehn and Yahr stage 2-3 idiopathic Parkinson's disease who have
      fallen in the past year. Participants will be randomised to two groups, receiving
      either rivastigmine capsules or identical placebo capsules for 8 months.
      Assessment will be undertaken at baseline and at the end of medication
      prescription (i.e. 8 months) with participants remaining enrolled in the trial
      for a further 4 months to monitor for falls and adverse events. The primary
      outcome is step time variability, assessed with and without the addition of
      concurrent cognitive tasks. Secondary outcomes will include other gait
      parameters, sensorimotor and balance performances, cognitive indices, falls and
      fall related injury, fear of falling, Parkinson's symptoms and data pertaining to
      possible harms. DISCUSSION: This randomised controlled trial will examine the
      effect of cholinesterase inhibitor therapy on gait, balance and falls in
      Parkinson's disease. If effective, it would offer a new therapeutic option to
      ameliorating gait and cognitive deficits in a population at high risk of falls.
      TRIAL REGISTRATION: ISRCTN19880883, UTN U1111-1124-0244.

PMID- 24299498
TI  - Clinicopathological relevance of granular C4d deposition in peritubular
      capillaries of kidney allografts.
AB  - While linear C4d staining in peritubular capillaries (PTC) is established as a
      marker of antibody-mediated rejection, the significance of a distinct granular
      C4d deposition pattern has not yet been clarified. In this study, 329 renal
      allograft recipients who underwent indication biopsies were analysed for
      immunohistochemical C4d staining characteristics. Fifty-six (17%) recipients
      showed granular C4d in PTC, without any relationship to conventional risk factors
      and morphological features of rejection. We found a strong association with long
      term overall graft survival (7-year survival: 41% vs. 66% in granular C4d
      negative subjects, P=0.001), which was mainly driven by a greater risk of
      mortality [hazard ratio: 3.12 (95% confidence interval: 1.23-7.94); P=0.02].
      Granular C4d was associated with delayed graft function [39% vs. 22% (C4d
      negative subjects), P=0.007], higher 1-year serum creatinine [median 2.1
      (interquartile range: 1.7-2.6) mg/dl vs. 1.6 (1.3-2.0) mg/dl, P=0.001] and a
      trend towards worse death-censored graft survival (P=0.07). In support of a role
      of capillary immune complex formation, granular C4d was associated with electron
      dense deposits in PTC basement membranes, which were occasionally accompanied by
      focally distributed capillary IgG deposits. In conclusion, our study suggests
      clinical relevance of detecting capillary granular C4d deposition. Our results
      point to a pathogenetic role of alloimmune-independent immune complex deposition.

PMID- 24299499
TI  - Enhanced accumulation of glycogen, lipids and polyhydroxybutyrate under optimal
      nutrients and light intensities in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - AIMS: Glycogen (GL) and lipids (LP) are efficient biofuel substrates, whereas
      polyhydroxybutyrate (PHB) is a potent biodegradable plastic. This study aimed to
      increase accumulation of these three compounds in Synechocystis sp. PCC 6803.
      METHODS AND RESULTS: Under autophototrophic growth, co-accumulation of the three
      compounds reached maximum level in a mid-stationary phase at 39.2% of dry weight
      (22.7% GL, 14.1% LP and 2.4% PHB). Nitrogen deprivation increased this to 61.5%
      (36.8% GL, 11.2% LP and 13.5% PHB), higher than that achieved by phosphorus,
      sulfur, iron or calcium deprivation. Combining nitrogen deprivation with 0.4%
      (w/v) glucose addition for heterophototrophic growth and optimizing the light
      intensity (200 MUmol photons m(-2) s(-1) ) synergistically enhanced combined
      accumulation to 71.1% of biomass (41.3% GL, 16.7% LP and 13.1% PHB), a higher
      level than previously reported in Synechocystis. However, the maximum
      coproductivity of GL, LP and PHB (at 0.72 g l(-1) ) was obtained in the 12-day
      heterophototrophic culture without nitrogen deprivation. CONCLUSION: Accumulation
      of GL, LP and PHB was enhanced under both autophototrophic and heterophototrophic
      conditions by optimizations of nutrient and light supplies. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study provides a means for increasing co-production of
      potent bioenergy substrates and useful biomaterials in Synechocystis which may
      also be applicable to other cyanobacteria.

PMID- 24299500
TI  - Optimal delivery of aerosols to infants during mechanical ventilation.
AB  - PURPOSE: The objective of this study was to determine optimal aerosol delivery
      conditions for a full-term (3.6 kg) infant receiving invasive mechanical
      ventilation by evaluating the effects of aerosol particle size, a new wye
      connector, and timing of aerosol delivery. METHODS: In vitro experiments used a
      vibrating mesh nebulizer and evaluated drug deposition fraction and emitted dose
      through ventilation circuits containing either a commercial (CM) or new
      streamlined (SL) wye connector and 3-mm endotracheal tube (ETT) for aerosols with
      mass median aerodynamic diameters of 880 nm, 1.78 MUm, and 4.9 MUm. The aerosol
      was released into the circuit either over the full inhalation cycle (T1 delivery)
      or over the first half of inhalation (T2 delivery). Validated computational fluid
      dynamics (CFD) simulations and whole-lung model predictions were used to assess
      lung deposition and exhaled dose during cyclic ventilation. RESULTS: In vitro
      experiments at a steady-state tracheal flow rate of 5 L/min resulted in 80-90%
      transmission of the 880-nm and 1.78-MUm aerosols from the ETT. Based on CFD
      simulations with cyclic ventilation, the SL wye design reduced depositional
      losses in the wye by a factor of approximately 2-4 and improved lung delivery
      efficiencies by a factor of approximately 2 compared with the CM device. Delivery
      of the aerosol over the first half of the inspiratory cycle (T2) reduced exhaled
      dose from the ventilation circuit by a factor of 4 compared with T1 delivery.
      Optimal lung deposition was achieved with the SL wye connector and T2 delivery,
      resulting in 45% and 60% lung deposition for optimal polydisperse (~1.78 MUm) and
      monodisperse (~2.5 MUm) particle sizes, respectively. CONCLUSIONS: Optimization
      of selected factors and use of a new SL wye connector can substantially increase
      the lung delivery efficiency of medical aerosols to infants from current values
      of <1-10% to a range of 45-60%.

PMID- 24299501
TI  - Comparing usability of NEXThaler((r)) with other inhaled corticosteroid/long
      acting beta2-agonist fixed combination dry powder inhalers in asthma patients.
AB  - BACKGROUND: Inhaler mishandling is a common issue among patients suffering from
      asthma and is associated with poor clinical outcomes and greater consumption of
      health-care resources. Ease of use can improve inhaler technique and, possibly,
      patients' preference for their inhaler device, which in turn may lead to better
      adherence to therapy. METHODS: This study investigated usability characteristics
      of NEXThaler((r)) versus two other dry powder inhalers (DPIs; Diskus((r)) and
      Turbuhaler((r))). Sixty-six adult patients with asthma (mean age 42.9+/-17.7
      years) and with no previous experience of using a DPI were included in a
      randomized crossover comparison of the three devices. The main measures of
      usability were the number of steps failed for each device and the number of
      people who were able to use the device successfully (effectiveness), the time it
      took patients to set up the device and the time to read the instructions for use
      (IFU; efficiency), and patient preferences (satisfaction). Inhaler technique was
      evaluated after the IFU leaflet was read. RESULTS: NEXThaler was found to be
      superior to the other two DPIs in terms of the number of device use failures
      (p<0.001), time to set up (p<0.001), and time to read IFU (p<0.001).
      Additionally, the proportion of participants who completed a successful
      inhalation without any errors at all was significantly higher for NEXThaler than
      for Diskus and Turbuhaler (p<0.001). Patients rated NEXThaler as the easiest to
      use and most preferred inhaler to own (p<0.001). CONCLUSIONS: NEXThaler displayed
      better usability compared with Diskus and Turbuhaler. The improved usability and
      higher satisfaction with the device may contribute to increased patient adherence
      to asthma treatment.

PMID- 24299502
TI  - Manufacturing and device options for the delivery of biotherapeutics.
AB  - Biotherapeutic aerosol formulations are an intense area of interest for systemic
      and local drug delivery. This article provides a short overview of typical
      factors required specifically for biotherapeutic aerosol formulation design, the
      processing options open for consideration, and the issue of inhalation device
      selection. Focusing on spray drying, four case studies are used to highlight the
      relevant issues, describing investigations into: (1) the mechanical stresses
      occurring in bacteriophage formulations during spray-dryer atomization; (2)
      modeling of the spray-dryer process and droplet drying kinetics, to assist
      process design and predictions of formulation stability; (3) a predictive
      approach to the design and processing of a five-component dry powder aerosol
      formulation; and (4) the survival of bacteriophages after pressurized metered
      dose inhaler atomization.

PMID- 24299503
TI  - Development of 1,8-naphthalimides as clathrin inhibitors.
AB  - We reported the first small molecule inhibitors of the interaction between the
      clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin
      inhibition1). Initial screening of a ~17 000 small molecule ChemBioNet library
      identified 1. Screening of an existing in-house propriety library identified four
      substituted 1,8-napthalimides as ~80-120 MUM clathrin inhibitors. Focused library
      development gave 3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide, potassium salt (18,
      IC50 ~ 18 MUM). A second library targeting the 4-aminobenzyl moiety was
      developed, and four analogues displayed comparable activity (26, 27, 28, 34 with
      IC50 values of 22, 16, 15, and 15 MUM respectively) with a further four (24, 25,
      32, 33) more active than 18 with IC50 values of 10, 6.9, 12, and 10 MUM,
      respectively. Docking studies rationalized the structure-activity relationship
      (SAR) with the biological data. 3-Sulfo-N-benzyl-1,8-naphthalimide, potassium
      salt (25) with an IC50 ~ 6.9 MUM, is the most potent clathrin terminal domain
      amphiphysin inhibitor reported to date. 

PMID- 24299504
TI  - Reply: To PMID 24274997.

PMID- 24299507
TI  - One-Year Prospective Study of 7-mm-Long Implants in the Mandible: Installation
      Technique and Crown/Implant Ratio of 1.5 or Less.
AB  - This study prospectively evaluated the clinical prognoses of short implants (7-mm
      long) in the mandible. We investigated the clinical prognosis of short implants
      in 20 patients (46 implants) according to the installation technique (submerged
      or nonsubmerged), installation depth (5.5-mm depth, 7-mm depth), and
      crown/implant ratio. We investigated the marginal bone loss and peri-implant soft
      tissue index 12 months after the final prosthetic delivery. Twelve months after
      prosthetic delivery, no statistically significant differences were observed in
      bone loss in relation to the type of installation technique, installation depth,
      or crown/implant ratio. The plaque index and pocket depth indexes were not
      influenced by the installation technique, installation depth, or crown/implant
      ratio. We observed marginal bone loss of 3.3 mm in 1 implant from the
      nonsubmerged group. The total 1-year success rate was 97.83%. Based on this 1
      year success rate, short implants had a good clinical prognosis, regardless of
      the installation technique, installation depth, or crown/implant ratio. 

PMID- 24299506
TI  - Anti-thyroid antibodies as a predictor of thyroid cancer.
AB  - BACKGROUND: Recent literature has suggested an association between autoimmune
      thyroiditis and papillary thyroid cancer. The aims of this study were to evaluate
      if positive thyroid antibodies are associated with thyroid carcinoma and to
      examine the role of thyroid antibodies in the management of thyroid nodules.
      METHODS: This is a database study of all patients undergoing thyroidectomy with
      recorded preoperative thyroid antibodies (autoantibodies to thyroglobulin and/or
      thyroid peroxidase) levels from 2010 to 2012. We analysed preoperative thyroid
      antibody levels, fine needle aspiration cytology (FNAC) results, type of thyroid
      surgery and final histopathology. RESULTS: There were 960 patients who underwent
      thyroidectomy with recorded preoperative thyroid antibodies. Of 960 patients, 784
      had preoperative FNAC of thyroid nodules. Final histopathology showed 758 benign
      and 202 malignant cases. As expected, there was a strong association between
      raised thyroid antibodies and lymphocytic thyroiditis on histology (P = 0.0001)
      (two-sided probability). Overall, positive thyroid antibodies were not found to
      be a predictor of thyroid carcinoma (P = 0.161) (two-sided probability). However,
      in patients with benign FNAC, positive thyroid antibodies increased the risk of
      thyroid malignancy (odds ratio 2.16; 95% confidence interval 1.11 to 4.21, P =
      0.027) (two-sided probability). CONCLUSION: Patients with positive thyroid
      antibodies have a greater risk of malignancy in those with benign FNAC. We
      recommend routine thyroid antibody assessment in addition to FNAC as part of the
      assessment of thyroid nodules.

PMID- 24299509
TI  - Testosterone deficiency, supplementation, and prostate cancer: maintaining a
      balanced perspective.

PMID- 24299508
TI  - Early life IgE responses in children living in the tropics: a prospective
      analysis.
AB  - BACKGROUND: There are few birth cohort studies analyzing IgE sensitization in the
      tropics. OBJECTIVES: We aimed to describe the evolution of total IgE and specific
      IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort
      (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their
      relationships with wheezing. METHODS: Total and specific IgE were measured by
      ImmunoCap in mothers and children at four different time points (S1-S4) between 0
      and 42 months. Parasite infection was evaluated by stool examination. RESULTS:
      Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic
      factors were associated with high cord blood (CB) total IgE. High CB total IgE
      was positively associated with higher Blomia tropicalis and Ascaris-specific IgE
      values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI:
      0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around
      3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides
      pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions
      were risk factors for HDM and Ascaris sensitization in children. A weak
      statistical association between B. tropicalis-specific IgE and ever wheezing was
      found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). CONCLUSIONS: In a
      socioeconomically deprived community from the tropics, sensitization to HDM
      allergens was very frequent at early life, especially to B. tropicalis. In
      contrast to expected according to the hygiene hypothesis, unhygienic/poverty
      conditions were risk factors for allergen sensitization. High CB total IgE levels
      were a risk factor for allergen sensitization but protected from recurrent
      wheezing.

PMID- 24299511
TI  - Sexual enhancement products.

PMID- 24299512
TI  - What is being promoted? Hospital nurse knowledge of health in Jordan.
AB  - PURPOSE: The study examined the level of knowledge of health among hospital
      nurses in Jordan. Four focus group discussions were carried out with hospital
      nurses. The findings identified three themes: health as the freedom from illness,
      health as good social and psychological well-being, and health as a good
      environment to live in. The nurses in this study had no knowledge of spiritual
      and socioeconomic aspects of health. Our study shows that nurses' knowledge of
      health is often triggered by casework as opposed to a general learning of health
      related issues. IMPLICATIONS FOR NURSING PRACTICE: Hospital nurses in health
      promotion are unlikely to be very knowledgeable until they fully have a coherent
      understanding of sociocultural and environmental determinants of health.

PMID- 24299513
TI  - A randomized controlled trial of larval therapy for the debridement of leg
      ulcers: results of a multicenter, randomized, controlled, open, observer blind,
      parallel group study.
AB  - It has been known for centuries that the application of larvae is useful to heal
      certain wounds by facilitating debridement of necrotic tissue,(1) yet the
      efficacy of larval therapy continues to be debatable. This study compared the
      clinical effectiveness of a larval therapy dressing (BioFOAM) with a standard
      debridement technique (Purilon gel; hydrogel) in terms of time to debridement of
      venous (VLU) or mixed arterial/venous (MLU) leg ulcers. Data analyses were
      conducted on 88 subjects. Sixty-four subjects completed the full study. Of these,
      31 of the 32 (96.9%) patients who completed treatment in the larvae arm debrided
      fully, compared with 11 of the 32 (34.4%) patients who completed the hydrogel
      arm. In addition, 42 (48%) ulcers fully debrided within the 21-day intervention
      phase, 31 (67.4%) from the larvae arm (n = 46), and 11 (26.2%) from the hydrogel
      arm (n = 42), which was statistically significant (p = 0.001) in support of
      larvae. A statistically significant difference was also observed between
      treatment arms with regard to numbers of dressing changes during the intervention
      phase of the study (p < 0.001) in that subjects in the larvae arm required
      significantly fewer dressing changes(mean = 2.83) than those in the hydrogel arm
      (mean = 5.40). There were no statistically significant differences in the
      clinical condition of the wound bed and surrounding skin by intervention.
      Subjects in the larvae arm experienced more ulcer-related pain or discomfort than
      subjects in the hydrogel arm (p < 0.001). This study provided good evidence to
      show that larval therapy, in the form of a BioFOAM dressing, debrided VLU and MLU
      considerably more quickly than a hydrogel, although the possibility of
      resloughing should be closely monitored. 

PMID- 24299514
TI  - miR-199a-5p silencing regulates the unfolded protein response in chronic
      obstructive pulmonary disease and alpha1-antitrypsin deficiency.
AB  - RATIONALE: Retention of abnormal alpha1-antitrypsin (AAT) activates the unfolded
      protein response in AAT-deficient monocytes. The regulatory role of microRNAs
      (miRNAs) in unfolded protein responses and chronic obstructive pulmonary disease
      pathogenesis has not been investigated. OBJECTIVES: To investigate miRNA
      expression and function in MM and ZZ monocytes and identify miRNA(s) regulating
      the unfolded protein response. METHODS: Peripheral blood monocytes were isolated
      from asymptomatic and symptomatic MM and ZZ individuals for miRNA expression
      profiling and pyrosequencing analysis. miRNA/gene and protein expression was
      measured with quantitative polymerase chain reaction and Western blotting.
      Overexpression and inhibition studies were performed with pre-miR or anti-miR,
      respectively. Luciferase reporter genes were used to elucidate direct miRNA
      target interactions. Inflammatory cytokines were detected using the Meso Scale
      Discovery Plex assays. MEASUREMENTS AND MAIN RESULTS: Forty-three miRNAs were
      differentially expressed, with miR-199a-5p most highly up-regulated in
      asymptomatic ZZ versus MM monocytes. miR-199a-2 promoter hypermethylation
      inhibits miR-199a-5p expression and was increased in symptomatic MM and ZZ
      monocytes compared with asymptomatic counterparts. GRP78, activating
      transcription factor 6, p50, and p65 were increased in symptomatic versus
      asymptomatic ZZ monocytes. Reciprocal down- or up-regulation of these markers was
      observed after miRNA modulation. Direct miR-199a-5p targeting of activating
      transcription factor 6, p50, and p65 by miR-199a-5p was demonstrated using
      luciferase reporter systems. Overexpression of miR-199a-5p also decreased other
      arms of the UPR and expression of cytokines that are not putative targets.
      CONCLUSIONS: miR-199a-5p is a key regulator of the unfolded protein response in
      AAT-deficient monocytes, and epigenetic silencing of its expression regulates
      this process in chronic obstructive pulmonary disease.

PMID- 24299515
TI  - The discovery and development of vandetanib for the treatment of thyroid cancer.
AB  - INTRODUCTION: Thyroid cancer represents over 90% of all endocrine malignancies,
      with medullary thyroid carcinoma (MTC) accounting for 5 - 9% of them. Patients
      with early-stage disease have a favorable prognosis, but once distant metastasis
      develops, survival drops to 50% or less. Although surgery remains effective for
      early-stage disease, patients with advanced disease pose a challenge as
      traditional therapies have not provided long-term benefits. Vandetanib, initially
      developed to target other receptors, demonstrated anti-rearranged during
      transfection (anti-RET) kinase activity. This led to preclinical studies followed
      by recent human clinical trials, culminating in its FDA approval in April 2011
      for application in the treatment of symptomatic or progressive MTC in patients
      with surgically unresectable, locally advanced or metastatic disease. AREAS
      COVERED: The authors provide a review of the discovery strategy and preclinical
      development of vandetanib. The authors also provide some insight into the
      clinical development and the drug's post-launch situation. EXPERT OPINION:
      Vandetanib has been shown to improve progression-free survival in MTC patients,
      but its impact on overall survival is still inconclusive. Further data analysis
      will be needed to answer the question of whether it impacts overall survival in
      MTC. Despite its advancements, vandetanib still lacks durable efficacy, carries
      moderate toxicity and has issues with drug resistance over time, not to mention
      issues of cost. There is a significant need for additional research to discover
      and develop improved therapeutic strategies for this difficult disease.

PMID- 24299516
TI  - The 'robustness' of vocabulary intervention in the public schools: targets and
      techniques employed in speech-language therapy.
AB  - This study examined vocabulary intervention-in terms of targets and techniques
      for children with language impairment receiving speech-language therapy in public
      schools (i.e., non-fee-paying schools) in the United States. Vocabulary
      treatments and targets were examined with respect to their alignment with the
      empirically validated practice of rich vocabulary intervention. Participants were
      forty-eight 5-7-year-old children participating in kindergarten or the first
      grade year of school, all of whom had vocabulary-specific goals on their
      individualized education programmes. Two therapy sessions per child were coded to
      determine what vocabulary words were being directly targeted and what techniques
      were used for each. Study findings showed that the majority of words directly
      targeted during therapy were lower-level basic vocabulary words (87%) and very
      few (1%) were academically relevant. On average, three techniques were used per
      word to promote deep understanding. Interpreting findings against empirical
      descriptions of rich vocabulary intervention indicates that children were exposed
      to some but not all aspects of this empirically supported practice. 

PMID- 24299517
TI  - Impact of radiotherapy in the management of locally advanced extrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: Optimal therapy for patients with unresectable locally advanced
      extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the
      role of radiotherapy in the management of such tumors. METHODS: We
      retrospectively reviewed the charts of patients treated in our institution with
      conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent
      chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor
      (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25
      patients assessable for EBRT response, we observed 9 complete responses, 4
      partial responses, 10 stabilisations, and 2 progressions. The median follow-up
      was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was
      metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p
      = 0.25). Twenty-eight patients (93%) died of relapse or disease complications.
      Median overall survivals in the whole group and in group 1 or 2 were respectively
      12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals
      were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67%
      and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC,
      with acceptable toxicity. For primary disease, the high rate of metastatic
      relapse suggests to limit EBRT to non-progressive patients after induction
      chemotherapy.

PMID- 24299518
TI  - Impact of post-transplant flow cytometric panel-reactive antibodies on late-onset
      hepatic venous outflow obstruction following pediatric living donor liver
      transplantation.
AB  - The development of late-onset hepatic venous outflow obstruction (LOHVOO)
      following pediatric living donor liver transplantation (LDLT) can lead to
      uncontrollable fibrotic damage in liver grafts, even long-term patency of the
      graft outflow is achieved with appropriate therapeutic modalities. The aim of
      this study was to verify our hypothesis that some immunological responses,
      particularly cellular and/or antibody-mediated rejection (AMR), are associated
      with LOHVOO, which occurs following damage to liver sinusoidal endothelial cells
      in zone 3 of liver grafts. One hundred and eighty-nine patients underwent LDLT
      between May 2001 and December 2010 at our institute. Nine patients (4.8%) were
      identified as having LOHVOO. The preoperative factors, operative factors, and
      mortality, morbidity, and survival rates were examined and compared between the
      groups with and without LOHVOO. No statistical differences were observed between
      the groups with regard to preoperative factors, technical factors, or
      postoperative complications. However, FlowPRA reactivity was found to be a
      statistically significant risk factor for LOHVOO (P=0.006). The patients with
      both class I- and class II-reactive antibodies also had a significant risk of
      developing LOHVOO (P=0.03) and exhibited significantly higher retransplant rates.
      In conclusion, although further studies are needed to clarify this phenomenon,
      the pathophysiological mechanism underlying the development of LOHVOO after LDLT
      may be explained by immune-mediated responses that facilitate damage in zone 3 of
      liver grafts.

PMID- 24299520
TI  - Tubular variant of basal cell adenoma shares immunophenotypical features with
      normal intercalated ducts and is closely related to intercalated duct lesions of
      salivary gland.
AB  - AIMS: The morphological criteria for identification of intercalated duct lesions
      (IDLs) of salivary glands have been defined recently. It has been hypothesised
      that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of
      histological patterns, and the tubular variant is the one that presents the
      strongest resemblance with IDLs. The aim of this study was to analyse the
      morphological and immunohistochemical profiles of IDLs and BCAs classified into
      tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA
      represent distinct entities. METHODS AND RESULTS: Eight IDLs, nine tubular BCAs
      and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas,
      which represented 20-70% of the tumour. In non-tubular BCA, IDL-like areas were
      occasional and small (<5%). One patient presented IDLs, tubular BCAs and
      IDL/tubular BCA combined lesions. Luminal ductal cells of IDLs and tubular BCAs
      exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA
      group, few luminal cells exhibited such an immunoprofile; they were mainly CK14
      positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs
      were positive for CK14, calponin, alpha-SMA and p63; they were more numerous in
      BCA lesions. CONCLUSIONS: IDL, tubular BCA and non-tubular BCA form a continuum
      of lesions in which IDLs are related closely to tubular BCA. In both, the
      immunoprofile of luminal and myoepithelial cells recapitulates the normal
      intercalated duct. The difference between the adenoma-like subset of IDLs and
      tubular BCA rests mainly on the larger numbers of myoepithelial cells in the
      latter. Our findings indicate that at least some BCAs can arise via IDLs.

PMID- 24299519
TI  - Parallel evolution of local adaptation and reproductive isolation in the face of
      gene flow.
AB  - Parallel evolution of similar phenotypes provides strong evidence for the
      operation of natural selection. Where these phenotypes contribute to reproductive
      isolation, they further support a role for divergent, habitat-associated
      selection in speciation. However, the observation of pairs of divergent ecotypes
      currently occupying contrasting habitats in distinct geographical regions is not
      sufficient to infer parallel origins. Here we show striking parallel phenotypic
      divergence between populations of the rocky-shore gastropod, Littorina saxatilis,
      occupying contrasting habitats exposed to either wave action or crab predation.
      This divergence is associated with barriers to gene exchange but, nevertheless,
      genetic variation is more strongly structured by geography than by ecotype. Using
      approximate Bayesian analysis of sequence data and amplified fragment length
      polymorphism markers, we show that the ecotypes are likely to have arisen in the
      face of continuous gene flow and that the demographic separation of ecotypes has
      occurred in parallel at both regional and local scales. Parameter estimates
      suggest a long delay between colonization of a locality and ecotype formation,
      perhaps because the postglacial spread of crab populations was slower than the
      spread of snails. Adaptive differentiation may not be fully genetically
      independent despite being demographically parallel. These results provide new
      insight into a major model of ecologically driven speciation. 

PMID- 24299521
TI  - A comparison of anaesthetic recoveries in cats following induction with either
      alfaxalone or ketamine and diazepam.
AB  - AIM: To determine if cats anaesthetised with alfaxalone have different recoveries
      to cats anaesthetised with a combination of ketamine and diazepam. METHODS:
      Anaesthesia for ovariohysterectomy was induced in cats with either alfaxalone
      (n=23) or a combination of ketamine and diazepam (n=22). All cats were
      premedicated with combinations of acepromazine and morphine. Recoveries were
      scored using a categorical grading scheme applied to 18 parameters over 60
      minutes following extubation. The parameters scored covered movement, sensitivity
      to touch, sound and light, body position, sneezing and vocalisation. One person
      scored all recoveries and they were blinded to the induction drug used. Scores
      were compared between drugs at different times using the Kruskal-Wallis rank sum
      test. RESULTS: Recovery scores were not normally distributed. Analysis of the
      data using the Kruskal-Wallis rank sum test revealed that cats induced with
      alfaxalone showed an increase in recovery scores at 5 minutes for pawing at the
      head (p=0.001). No parameters differed significantly at 10 and 20 minutes. For
      cats anaesthetised with ketamine and diazepam there was an increase at 30 minutes
      in pacing, jerky sudden movements, unsettledness and increased sensitivity to
      touch at the surgical site and on the head (p<=0.01). At 60 minutes cats
      anaesthetised with ketamine and diazepam still showed an increase in
      unsettledness compared to those cats anaesthetised with alfaxalone (p=0.005).
      CONCLUSIONS: The results suggest that recoveries of cats following alfaxalone
      induction are significantly different to recoveries after induction with ketamine
      and diazepam. Overall, cats induced with ketamine and diazepam had more active
      and unsettled recoveries than alfaxalone over the 60-minute period observed.
      CLINICAL RELEVANCE: Cats recovering from alfaxalone anaesthesia have more settled
      recoveries than cats recovering from ketamine and diazepam anaesthesia. If a
      quiet settled recovery is desired following a surgical procedure, alfaxalone is
      likely to be a better choice than ketamine and diazepam.

PMID- 24299522
TI  - Proven invasive pulmonary mucormycosis successfully treated with amphotericin B
      and surgery in patient with acute myeloblastic leukemia: a case report.
AB  - INTRODUCTION: Invasive mucormycosis (zygomycosis) is the third most frequent
      fungal infection in patients with hematologic malignancies. It often results in a
      fatal outcome mainly due to the difficulty of early diagnosis and its resistance
      to antimycotics. CASE PRESENTATION: A 52-year-old Caucasian man was diagnosed
      with acute myeloblastic leukemia. Following the induction chemotherapy he
      developed febrile neutropenia. Meropenem (3*1000mg/day) was introduced
      empirically. A chest computed tomography showed soft-tissue consolidation change
      in his right upper lobe. A bronchoscopy was performed and the histology indicated
      invasive pulmonary aspergillosis based on fungal hypha detection. Also, high risk
      patients are routinely screened for invasive fungal infections using commercially
      available serological enzyme-linked immunosorbent assay tests: galactomannan and
      mannan (Bio-Rad, France), as well as anti-Aspergillus immunoglobulin G and/or
      immunoglobulin M and anti-Candida immunoglobulin G and/or immunoglobulin M
      antibodies (Virion-Serion, Germany). Galactomannan showed low positivity and
      voriconazole therapy (2*400mg/first day; 2*300mg/following days) was implemented.
      The patient became afebrile and a partial remission of disease was established.
      After 2 months, the patient developed a fever and a chest multi-slice computed
      tomography showed soft-tissue mass compressing his upper right bronchus.
      Voriconazole (2*400mg/first day; 2*300mg/following days) was reintroduced and
      bronchoscopy was repeated. Histologic examination of the new specimen was done,
      as well as a revision of the earlier samples in the reference laboratory and the
      diagnosis was switched to invasive pulmonary mucormycosis. The treatment was
      changed to amphotericin B colloidal dispersion (1*400mg/day). The complete
      remission of acute myeloblastic leukemia was verified after 2 months. During his
      immunerestitution, a high positivity of the anti-Aspergillus immunoglobulin M
      antibodies was found in a single serum sample and pulmonary radiography was
      unchanged. A lobectomy of his right upper pulmonary lobe was done and the
      mycology culture of the lung tissue sample revealed Rhizopus oryzae. He remained
      in complete remission for more than 1 year. CONCLUSIONS: Invasive mucormycosis
      was successfully treated with amphotericin B, surgery and secondary itraconazole
      prophylaxis. As a rare disease invasive mucormycosis is not well understood by
      the medical community and therefore an improvement of education about prevention,
      diagnosis and treatment of invasive mucormycosis is necessary.

PMID- 24299523
TI  - Why write?

PMID- 24299524
TI  - Following in the footsteps of David Barker: the association between extreme
      prematurity and atopic dermatitis risk.

PMID- 24299525
TI  - Burning issues in the diagnosis of xeroderma pigmentosum.

PMID- 24299526
TI  - Interpreting outcome measures and defining treatment success.

PMID- 24299527
TI  - Research in Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN): a network
      of specialist TEN centres is needed to undertake effective clinical studies and
      therapeutic trials.

PMID- 24299528
TI  - Biologic therapy for psoriasis: early response implies future success.

PMID- 24299531
TI  - Multidisciplinary team simulation for the operating theatre: a review of the
      literature.
AB  - INTRODUCTION: Analyses of adverse events inside the operating theatre has
      demonstrated that many errors are caused by failure in non-technical skills and
      teamwork. While simulation has been used successfully for teaching and improving
      technical skills, more recently, multidisciplinary simulation has been used for
      training team skills. We hypothesized that this type of training is feasible and
      improves team skills in the operating theatre. METHODS: A systematic search of
      the literature for studies describing true multidisciplinary operating theatre
      team simulation was conducted in November and December 2012. We looked at the
      characteristics and outcomes of the team simulation programmes. RESULTS: 1636
      articles were initially retrieved. Utilizing a stepwise evaluation process, 26
      articles were included in the review. The studies reveal that multidisciplinary
      operating theatre simulation has been used to provide training in technical and
      non-technical skills, to help implement new techniques and technologies, and to
      identify latent weaknesses within a health system. Most of the studies included
      are descriptions of training programmes with a low level of evidence. No
      randomized control trial was identified. Participants' reactions to the training
      programme were positive in all studies; however, none of them could objectively
      demonstrate that skills acquired from simulation are transferred to the operating
      theatre or show a demonstrable benefit in patient outcomes. CONCLUSION:
      Multidisciplinary operating room team simulation is feasible and widely accepted
      by participants. More studies are required to assess the impact of this type of
      training on operative performance and patient safety.

PMID- 24299535
TI  - The case against the use of dental implants in dogs and cats.

PMID- 24299536
TI  - What is your diagnosis? Foreign body.

PMID- 24299537
TI  - Diagnostic imaging in veterinary dental practice. Dental disease in a cat.

PMID- 24299538
TI  - Animal behavior case of the month. Separation anxiety.

PMID- 24299539
TI  - Pathology in practice. Ichthyosis in an alpaca.

PMID- 24299540
TI  - Pathology in practice. Ehrlichia-Hepatozoon coinfection in a dog.

PMID- 24299542
TI  - Serial serum feline pancreatic lipase immunoreactivity concentrations and
      prognostic variables in 33 cats with pancreatitis.
AB  - OBJECTIVE: To identify factors significantly associated with prognosis in cats
      hospitalized because of pancreatitis. DESIGN: Prospective case series. Animals-33
      cats hospitalized for treatment of pancreatitis (diagnosis determined on the
      basis of clinical signs and serum feline pancreatic lipase immunoreactivity
      [fPLI] concentration >= 5.4 MUg/L). PROCEDURES: Cats were hospitalized (day 1)
      for 2 to 16 days and observed for 44 days or until they died or were euthanized.
      Results of physical examination and hematologic and serum biochemical analysis,
      including measurement of serum fPLI concentration, performed on the day of
      hospital admission were analyzed to determine whether they were associated with
      outcome (ie, survival to at least 44 days vs death or euthanasia). RESULTS: On
      day 1, mean * SD serum fPLI concentration among the 33 cats was 22.0 * 16.4
      MUg/L. Mean age of the cats was 12.7 * 3.8 years (range, 4 to 19 years). Eleven
      of the 33 (33%) cats died or were euthanized before day 44. In univariate
      analyses, dyspnea, hypothermia, hypokalemia, hyperkalemia, and serum fPLI
      concentration were significantly associated with an adverse outcome. However, in
      a multivariate analysis, only severe dyspnea, hyperkalemia (potassium
      concentration > 5.5 mmol/L), and serum fPLI concentration at the time of hospital
      admission were found to be significantly associated with an adverse outcome.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dyspnea, hyperkalemia,
      and serum fPLI concentration at the time of hospital admission were significant
      prognostic factors for cats hospitalized because of pancreatitis.

PMID- 24299543
TI  - Diagnostic accuracy of a point-of-care urine bacteriologic culture test in dogs.
AB  - OBJECTIVE: To determine diagnostic accuracy of a compartmented bacteriologic
      culture and antimicrobial susceptibility testing plate (CCSP) for detection of
      bacterial urinary tract infection (UTI) in dogs and antimicrobial susceptibility
      testing of bacterial isolates. DESIGN: Evaluation study. SAMPLE: 62 frozen,
      previously characterized bacterial isolates from canine urine cultures and 147
      canine urine samples. PROCEDURES: The study was conducted in 2 phases:
      preliminary assay validation (phase 1) and diagnostic validation (phase 2). For
      phase 1, the frozen bacterial isolates were revitalized and tested with the CCSP
      and with standard aerobic microbiological culture (SAMC). For phase 2, the urine
      samples were tested with the CCSP and SAMC in parallel. RESULTS: For phase 1,
      after 24 hours of culture, 46 of 62 (74%) bacterial isolates had growth on the
      CCSP and all (100%) had growth in SAMC. For bacterial isolates with growth, the
      CCSP allowed correct identification of 45 of 46 (98%) isolates. Isolates yielding
      no growth on the CCSP were gram-positive cocci (Staphylococcus spp [n = 7] and
      Enterococcus spp [9]). In phase 2, the overall diagnostic accuracy of the CCSP,
      compared with SAMC, was 94% (sensitivity, 81%; specificity, 99%). The positive
      predictive value was 98% and negative predictive value was 92%. Susceptibility
      results for enrofloxacin and trimethoprim-sulfamethoxazole as determined with the
      CCSP had greatest concordance with those determined by SAMC (71% and 96%,
      respectively), compared with other antimicrobial susceptibilities. CONCLUSIONS
      AND CLINICAL RELEVANCE: Use of the CCSP led to accurate exclusion of UTI in dogs
      without a UTI but was less reliable for diagnosis of UTI, particularly infections
      caused by gram-positive cocci. Standard aerobic microbiological culture remains
      the gold standard for detection of UTI in dogs.

PMID- 24299544
TI  - Co-occurrence of potentially preventable factors in 256 dog bite-related
      fatalities in the United States (2000-2009).
AB  - OBJECTIVE: To examine potentially preventable factors in human dog bite-related
      fatalities (DBRFs) on the basis of data from sources that were more complete,
      verifiable, and accurate than media reports used in previous studies. DESIGN:
      Prospective case series. SAMPLE: 56 DBRFs occurring in the United States from
      2000 to 2009. PROCEDURES: DBRFs were identified from media reports and detailed
      histories were compiled on the basis of reports from homicide detectives, animal
      control reports, and interviews with investigators for coding and descriptive
      analysis. RESULTS: Major co-occurrent factors for the 256 DBRFs included absence
      of an able-bodied person to intervene (n = 223 [87.1%]), incidental or no
      familiar relationship of victims with dogs (218 [85.2%]), owner failure to neuter
      dogs (216 [84.4%]), compromised ability of victims to interact appropriately with
      dogs (198 [77.4%]), dogs kept isolated from regular positive human interactions
      versus family dogs (195 [76.2%]), owners' prior mismanagement of dogs (96
      [37.5%]), and owners' history of abuse or neglect of dogs (54 [21.1%]). Four or
      more of these factors co-occurred in 206 (80.5%) deaths. For 401 dogs described
      in various media accounts, reported breed differed for 124 (30.9%); for 346 dogs
      with both media and animal control breed reports, breed differed for 139 (40.2%).
      Valid breed determination was possible for only 45 (17.6%) DBRFs; 20 breeds,
      including 2 known mixes, were identified. CONCLUSIONS AND CLINICAL RELEVANCE:
      Most DBRFs were characterized by coincident, preventable factors; breed was not
      one of these. Study results supported previous recommendations for multifactorial
      approaches, instead of single-factor solutions such as breed-specific
      legislation, for dog bite prevention.

PMID- 24299545
TI  - Risk factors associated with struvite urolithiasis in dogs evaluated at general
      care veterinary hospitals in the United States.
AB  - OBJECTIVE: To identify factors associated with development of struvite
      urolithiasis in dogs evaluated at general care veterinary hospitals in the United
      States. DESIGN: Retrospective case-control study. ANIMALS: 508 dogs with a first
      time diagnosis of struvite urolithiasis and 7,135 control dogs. PROCEDURES:
      Electronic medical records of all dogs evaluated at 787 general care veterinary
      hospitals in the United States between October 2007 and December 2010 were
      reviewed to identify dogs that developed struvite urolithiasis and 2 groups of
      control dogs with no history of urolithiasis. Information extracted included
      diet, age, sex, neuter status, breed size category, hospital location, and date
      of diagnosis. Urinalysis results, urolith composition, and other disease
      conditions were recorded if applicable. Potential risk factors were assessed with
      univariable and multivariable regression analysis. RESULTS: Toy- or small-sized
      breeds had significantly greater odds of struvite urolithiasis, compared with
      medium- or large-sized breeds. Neutering significantly increased the odds of this
      outcome in females only; sexually intact females were more likely to develop
      struvite urolithiasis than were sexually intact males, but only up to 5 years of
      age. Urinary factors significantly associated with the outcome were basic (vs
      acidic) pH, presence of RBCs or WBCs, protein concentration > 30 mg/dL, and
      ketone concentration >= 5 mg/dL. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation
      of demographic characteristics and urinalysis results may be useful in the early
      identification of struvite urolithiasis in dogs. Periodic urinalysis in dogs is
      recommended because of the potential health impact of a late diagnosis of
      urolithiasis.

PMID- 24299546
TI  - Idiopathic ischemic necrosis of an accessory carpal bone in a dog.
AB  - CASE DESCRIPTION: A 6-year-old neutered female mixed-breed dog was evaluated
      because of a 6-week history of left forelimb lameness that varied in severity.
      CLINICAL FINDINGS: Radiography revealed expansile and lytic changes of the left
      accessory carpal bone (ACB). Results of histologic evaluation of ACB core biopsy
      specimens indicated areas of bone necrosis. The entire left ACB was excised and
      submitted for histologic evaluation; results confirmed a diagnosis of idiopathic
      ischemic necrosis. TREATMENT AND OUTCOME: Left pancarpal arthrodesis was
      performed to treat carpal hyperextension and persistent lameness. The dog had an
      excellent functional outcome with no other problems related to the carpus until
      its death 4 years later, further decreasing suspicion that the problem was
      attributable to an undetected neoplasm or bacterial or fungal osteomyelitis.
      CLINICAL RELEVANCE: The radiographic and histologic findings for the dog of this
      report were similar to previously reported findings for dogs with ischemic
      femoral head necrosis and humans with ischemic carpal (pisiform or lunate bone)
      necrosis. The etiology of the ischemic ACB necrosis in this dog was not
      determined. To the authors' knowledge, this is the first report of a dog with
      idiopathic ischemic ACB necrosis. Idiopathic ischemic necrosis should be included
      as a differential diagnosis for dogs with lameness and destructive and expansile
      ACB radiographic lesions. An excellent functional outcome may be attained by
      means of ACB excision and pancarpal arthrodesis.

PMID- 24299547
TI  - Corneal sequestrum in a dog with chronic unilateral keratoconjunctivitis sicca.
AB  - CASE DESCRIPTION: A 14-year-old 8.2-kg (18.04-lb) castrated male Cairn Terrier
      with chronic keratoconjunctivitis sicca in the left eye was evaluated because of
      severe blepharospasm and a black plaque of 3 weeks' duration. CLINICAL FINDINGS:
      Abnormalities of the left eye included a decreased Schirmer tear test value and
      the presence of a brownish-black plaque in the center of the cornea. The plaque
      was surrounded by fibrovascular tissue except at the medial aspect where there
      was mild malacia of the adjacent corneal stroma. TREATMENT AND OUTCOME: The
      plaque was removed by superficial keratectomy, and a conjunctival graft was
      performed. Histologic evaluation of the plaque and surrounding cornea revealed
      ulceration, stromal necrosis, and chronic suppurative keratitis with fibrosis and
      neovascularization. Evaluation of plaque sections that were stained with Gram and
      Von-Kossa stains yielded negative results for bacteria and mineralization,
      respectively; examination of sections stained with periodic acid-Schiff stain
      revealed multiple intracytoplasmic inclusions in macrophages. Virus isolation and
      a PCR assay for canine herpesvirus yielded negative results. Transmission
      electron microscopy revealed collagen disruption with interspersed macrophages
      and apoptotic keratocytes; no viral particles or evidence of other infectious
      agents was observed. The graft healed without complication and was trimmed 2
      weeks after surgery. Four months after surgery, the Schirmer tear test value
      remained decreased from reference limits despite topical tacrolimus treatment,
      and pigmentary keratopathy was present surrounding the graft. CLINICAL RELEVANCE:
      Corneal sequestra are rare in species other than cats. In this dog, it was
      possible that chronic keratoconjunctivitis sicca might have contributed to the
      development of the corneal sequestrum.

PMID- 24299548
TI  - Usefulness of Doppler ultrasonography to assess digital vascular dynamics in
      horses with systemic inflammatory response syndrome or laminitis.
AB  - OBJECTIVE: To evaluate the usefulness of Doppler ultrasonography as a method to
      assess changes in digital vascular dynamics in horses with systemic inflammatory
      response syndrome (SIRS) or laminitis. DESIGN: Cross-sectional study. Animals-42
      adult Andalusian horses. PROCEDURES: Group 1 included 9 healthy horses, group 2
      included 19 horses with SIRS without (n = 9) or with (10) a palpable increase in
      digital pulse intensity, and group 3 included 14 horses with laminitis without
      (8) or with (6) radiographic evidence of rotation or distal displacement
      (sinking) of the third phalanx. Qualitative spectrum characteristics and
      quantitative Doppler measurements of the lateral palmar digital artery were
      obtained for horses in each group. RESULTS: 4 spectra, characterized by a
      positive systolic peak followed by several positive diastolic peaks, were
      observed in group 1 horses, group 2 horses, and group 3 horses that lacked
      radiographic changes. In the group 3 horses that had radiographic changes,
      laminar blood flow was detected. Diameter of the lateral palmar digital artery
      was significantly larger in the group 3 horses than in the group 2 horses; blood
      flow was significantly higher in the group 2 horses that had an increase in
      digital pulse intensity than in the group 2 horses without an increase in digital
      pulse intensity; velocity-time integral and acceleration time were significantly
      lower in group 3 horses, compared with group 2 horses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that Doppler ultrasonography may be a useful
      complementary tool to detect digital blood flow changes of horses with SIRS,
      especially if they have a palpable increase in digital pulse intensity, or
      laminitis.

PMID- 24299549
TI  - Diagnoses, clinical pathology findings, and treatment outcome of geriatric
      horses: 345 cases (2006-2010).
AB  - OBJECTIVE: To compare clinical, clinical pathology, and outcome variables between
      geriatric and nongeriatric horses. DESIGN: Retrospective case-control study.
      ANIMALS: 690 horses (345 horses >= 20 years old and 345 horses > 1 and < 20 years
      old) examined at a referral hospital. PROCEDURES: Medical records were examined,
      and data collected included horse description, diagnosis, outcome, and CBC and
      serum biochemical analysis results. Cases were horses >= 20 years old, and
      controls were horses > 1 and < 20 years old. RESULTS: Mean +/- SD age was 23.9 +/
      4.6 years for cases and 9.2 +/- 3.6 years for controls. Arabian and pony breeds
      were significantly overrepresented in the geriatric group, compared with the
      control group. Diagnoses related to the digestive system, musculoskeletal system,
      and respiratory system were most common in this hospital population overall
      (cases and controls). Colic was the most common health problem overall. Digestive
      system disorders were significantly more prevalent among cases. Short-term
      survival rates for most categories of colic were no different for cases than for
      controls, with the exception of the category idiopathic colic. Considering all
      conditions, cases were significantly more likely to be nonsurvivors than were
      controls. Minor differences in serum biochemical results were found in some
      disease subcategories. Geriatric horses with colic were not more commonly
      euthanized than were adult nongeriatric horses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that in this population of horses in a referral
      hospital, age was associated with the prevalence of specific disease conditions.
      Few differences between cases and controls were found in serum biochemical
      values.

PMID- 24299550
TI  - Controlled oxygen release from pyridone endoperoxides promotes cell survival
      under anoxic conditions.
AB  - In tissue engineering, survival of larger constructs remains challenging due to
      limited supply of oxygen caused by a lack of early vascularization. Controlled
      release of oxygen from small organic molecules represents a possible strategy to
      prevent cell death under anoxic conditions. A comprehensive study of methylated
      pyridone-derived endoperoxides has led to the development of water-soluble
      molecules that undergo retro-Diels-Alder reactions in aqueous environment
      releasing oxygen in high yield and with half-lives of up to 13 h. These molecules
      in combination with vitamin C as singlet oxygen quencher significantly improved
      survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen
      depleted conditions. 

PMID- 24299551
TI  - Exposure to home and school environmental triggers and asthma morbidity in
      Chicago inner-city children.
AB  - BACKGROUND: In children, asthma hospitalization rates are highest among those
      aged 0-4 yr, indicating more acute and/or severe asthma exacerbations in younger
      children. We investigated the relationship between indoor exposures and three
      asthma morbidity measures in children of different age groups (0-4, 5-11, and 12
      yr of age or older). Identifying the factors leading to asthma morbidity in
      specific subgroups may lead to a better understanding of the disease and
      contribute to the development of effective interventions tailored to subgroups.
      METHODS: Children between 0 and 18 yr of age with asthma were enrolled in an
      asthma intervention program. At enrollment, hospitalizations, emergency room
      visits (ED), asthma night symptoms, and exposure to conditions in the child's
      home and school/daycare related to indoor allergens were collected using
      standardized questionnaires. Associations of exposure with the three asthma
      outcomes were estimated using logistic regression, stratified by age group.
      RESULTS: Of 246 children enrolled, the youngest age group had more
      hospitalizations in the past year, more ED visits in the past year, and more
      night awakenings in the past month due to asthma than the oldest two age groups
      (p = 0.02; p < 0.0001; and p = 0.01, respectively). Overall, more associations of
      exposures to home triggers were found with hospitalization in children aged 0-11
      yr, while classroom triggers were more likely to be associated with
      hospitalizations among the oldest two groups, 5-18 yr of age. CONCLUSIONS:
      Examining the relationship of specific environmental exposures with asthma
      exacerbations and hospitalizations across age group and in different indoor
      environments warrants further study.

PMID- 24299552
TI  - A Retrospective Study on Immediate Placement of Neoss Implants with Early Loading
      of Full-Arch Bridges.
AB  - BACKGROUND: Full-arch clearances of compromised teeth and placement of implant
      supported prostheses is one solution for the prosthetic rehabilitation of
      partially dentate patients. PURPOSE: To retrospectively evaluate treatment
      outcomes after full clearance, immediate placement, and early loading of full
      arch fixed bridges. MATERIALS AND METHODS: Fifty-five patients subjected to full
      clearance and placement of 284 Neoss implants (BimodalTM and ProactiveTM, Neoss
      Ltd, Harrogate, UK) in 29 edentulous maxillae and 26 mandibles for early loading
      (1 to 3 days) of a provisional full-arch bridge were retrospectively evaluated
      after 1 to 6 years of loading. OsstellTM measurements (Osstell AB, Goteborg,
      Sweden) were taken at placement and after 3 to 9 months when the provisional
      bridge was replaced with a permanent one. Marginal bone levels were measured in
      intraoral radiographs. RESULTS: All patients (100%) wore a fixed bridge at the
      time of finalizing the study. A total of 18 failures (6.3%) were encountered
      during the follow-up, giving an overall cumulative survival rate of 93.7%. All
      failures occurred in the maxilla (10.6%), and no implants were lost in the
      mandible. More BimodalTM (9.0%) than ProactiveTM (4.1%) implants failed. Failing
      implants showed a significantly lower mean primary stability than successful ones
      (p = .015). Failed cases showed a significantly lower average ISQ for all
      implants (p = .015) and a marked decrease to the second registration, while
      successful cases showed and maintained high ISQs. The average bone loss after 1
      year was 0.8 +/- 0.5 mm. CONCLUSIONS: Full-arch clearance of severely diseased
      teeth followed by immediate placement of Neoss implants, early loading with
      provisional full-arch bridges, and subsequent permanent bridges is a possible
      treatment modality for partially dentate patients. Caution with this approach is
      recommended for the maxilla, as opposed to the mandible.

PMID- 24299553
TI  - Clitoral vascularization and sexual behavior in young patients treated with
      drospirenone-ethinyl estradiol or contraceptive vaginal ring: a prospective,
      randomized, pilot study.
AB  - INTRODUCTION: Oral contraceptives (OC) are effective for birth control and have
      good cycle control and tolerability. However, the hormonal components could
      modify mood and libido. AIM: The aim of this study is to evaluate the genital
      vascular effects and sexual behavior of an OC containing 30 MUg ethinyl estradiol
      and 3 mg drospirenone in comparison with a flexible combined contraceptive
      vaginal ring. METHODS: Forty women underwent a sonographic assessment of the
      clitoral anatomy and vascularization and were administered the McCoy Female
      Sexuality Questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire
      (BDI). Estradiol, androstenedione, testosterone, and SHBG were assayed. Free
      Androgen Index (FAI) and Free Estrogen Index (FEI) were calculated. The patients
      were randomly submitted to OC (group I; n = 21) or vaginal ring (group II; n =
      19). MAIN OUTCOME MEASURES: Ultrasonographic clitoral volume, pulsatility index
      (PI) of dorsal clitoral arteries, MFSQ, BDI, and hormonal and biochemical assays
      were analyzed. RESULTS: After therapy, the testosterone levels were reduced in
      both groups, whereas estradiol decreased only in group I women. The SHBG
      increased in all the subjects, and both FAI and FEI decreased. The clitoral
      volume decreased in all the women. The PI of the dorsal clitoral artery increased
      only in patients on OC. The hormonal contraception was associated, in both
      studied groups, with a significant decrease of the two-factor Italian MFSQ score,
      which was more marked in OC users. In group I subjects, there was a reduction of
      the number of intercourse/week and a reduction of orgasm frequency during
      intercourse. The pain during intercourse worsened after OC use. The vaginal ring
      users reported a vaginal wetness. CONCLUSIONS: Six-month treatment with hormonal
      contraception is associated with a diminished MFSQ score. However, the frequency
      of sexual intercourse and orgasm was reduced only by the use of OC. The OC use
      was associated with increased pain during intercourse.

PMID- 24299554
TI  - Reliability of an ELISA test for diagnosing oestrosis in Iberian ibex.
AB  - Oestrosis is one of the most prevalent parasitosis affecting the Iberian ibex,
      Capra pyrenaica . To date, both the diagnosis of oestrosis and the determination
      of the intensity of parasitism require the use of invasive methods (necropsy),
      which necessarily limit research possibilities. We analyzed the immune humoral
      response (IgM and IgG) against Oestrus ovis L. excretory/secretory larval
      antigens in 32 sera taken from Iberian ibex from the Sierra Nevada Natural Space
      (southern Spain). Three antigens were collected: L1OES (from L1 larvae), L2OES
      (L2), and L3OES (L3). Necropsy was considered as the gold standard. The
      percentage of ibexes harboring Oestrus spp. larvae was 88%, the mean intensity of
      parasitism being 16.96 +/- 14.96 larvae per parasitized host (range: 2-52). In
      our sample, first-instar larvae (L1) were found in 9% of ibexes, while 69% of
      hosts carried L2 larvae and 88% L3 larvae. Positive correlations between L1 and
      L2 numbers, and between L2 and L3 numbers were detected. The best results with
      the immunoenzymatic assay were obtained using IgG antibodies against the L1OES
      antigens (specificity = 89%; sensitivity = 100%; positive predictive value =
      100%; negative predictive value = 57%). The IgG seroprevalence against L1OES was
      78%. Thus, the analysis of IgG antibodies against antigens collected from L1 O.
      ovis larvae would seem to be a noninvasive method for reliably diagnosing
      oestrosis in naturally infested Iberian ibex. Nevertheless, additional
      immunological and methodological advances are still required because false
      positive and false negative results still represent a non-negligible part of the
      results of the ELISA tests.

PMID- 24299556
TI  - Is attitude toward nursing diagnosis a determinant of its use?

PMID- 24299555
TI  - Interferon-gamma release assays and tuberculin skin testing for diagnosis of
      latent tuberculosis infection in healthcare workers in the United States.
AB  - RATIONALE: IFN-gamma release assays (IGRAs) are alternatives to tuberculin skin
      testing (TST) for diagnosis of latent tuberculosis infection. Limited data
      suggest IGRAs may not perform well for serial testing of healthcare workers
      (HCWs). OBJECTIVES: Determine the performance characteristics of IGRAs versus TST
      for serial testing of HCWs. METHODS: A longitudinal study involving 2,563 HCWs
      undergoing occupational tuberculosis screening at four healthcare institutions in
      the United States, where the average tuberculosis case rate ranged from 4 to 9
      per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT),
      and TST were performed at baseline and every 6 months for 18 months between
      February 2008 and March 2011. MEASUREMENTS AND MAIN RESULTS: A total of 2,418
      HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118
      (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with
      negative IGRAs was associated with bacillus Calmette-Guerin (BCG) vaccination
      (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions
      of participants with test conversion during the study period were 138 of 2,263
      (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for
      TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT
      vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of
      118 (77.1%), respectively, were negative when retested 6 months later. There was
      negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and
      for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. CONCLUSIONS:
      Most conversions among HCWs in low TB incidence settings appear to be false
      positives, and these occurred six to nine times more frequently with IGRAs than
      TST; repeat testing of apparent converters is warranted.

PMID- 24299558
TI  - Update on extended-release opioids in pain management.
AB  - Chronic pain is frequently treated with our most potent analgesics, the opioids.
      While immediate-release opioids given every 3 - 4 h provide adequate analgesia
      for most patients with cancer pain and some patients with chronic nonmalignant
      pain, extended-release (ER) opioid formulations have been developed in the hope
      that patients with chronic pain would have improved analgesia, reduced side
      effects, more convenience, improved compliance, improved sleep and reduced
      nighttime pain. A more recent goal of the ER opioid product is to reduce
      prescription opioid addiction risk. This editorial will review the evidence that
      modern ER opioid formulations have advanced toward these goals. 

PMID- 24299559
TI  - Early death after kidney transplantation--can the risk be reduced?

PMID- 24299557
TI  - The human liver fatty acid binding protein T94A variant alters the structure,
      stability, and interaction with fibrates.
AB  - Although the human liver fatty acid binding protein (L-FABP) T94A variant arises
      from the most commonly occurring single-nucleotide polymorphism in the entire
      FABP family, there is a complete lack of understanding regarding the role of this
      polymorphism in human disease. It has been hypothesized that the T94A
      substitution results in the complete loss of ligand binding ability and function
      analogous to that seen with L-FABP gene ablation. This possibility was addressed
      using the recombinant human wild-type (WT) T94T and T94A variant L-FABP and
      cultured primary human hepatocytes. Nonconservative replacement of the medium
      sized, polar, uncharged T residue with a smaller, nonpolar, aliphatic A residue
      at position 94 of the human L-FABP significantly increased the L-FABP alpha
      helical structure content at the expense of beta-sheet content and concomitantly
      decreased the thermal stability. T94A did not alter the binding affinities for
      peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ligands
      (phytanic acid, fenofibrate, and fenofibric acid). While T94A did not alter the
      impact of phytanic acid and only slightly altered that of fenofibrate on the
      human L-FABP secondary structure, the active metabolite fenofibric acid altered
      the T94A secondary structure much more than that of the WT T94T L-FABP. Finally,
      in cultured primary human hepatocytes, the T94A variant exhibited a significantly
      reduced extent of fibrate-mediated induction of PPARalpha-regulated proteins such
      as L-FABP, FATP5, and PPARalpha itself. Thus, while the T94A substitution did not
      alter the affinity of the human L-FABP for PPARalpha agonist ligands, it
      significantly altered the human L-FABP structure, stability, and conformational
      and functional response to fibrate. 

PMID- 24299560
TI  - Veterinary provision of analgesia for domestic cats (Felis catus) undergoing
      gonadectomy: a comparison of samples from New Zealand, Australia and the United
      Kingdom.
AB  - AIM: To compare the use and provision of analgesia to cats undergoing gonadectomy
      by a sample of veterinarians in New Zealand, Australia and the United Kingdom
      (UK). METHODS: Small animal veterinarians' views and practices on provision of
      analgesia to cats at three different time phases (pre/intra-operatively, post
      operatively and post-discharge) were gathered using an on-line questionnaire.
      Respondents were also asked to state the pharmacological agent(s) used and the
      dosage rate(s). Differences in provision of analgesia were assessed relative to
      the respondent using binary logistic regression. The effects of gender of the
      patient and time of provision were explored using McNewar's Test and Cochran's Q,
      respectively. Differences between drug types used amongst countries were tested
      using chi(2) analysis. RESULTS: There were 717 responses to the survey. Of these
      249 (34.7%) were from New Zealand, 269 (37.5%) were from the UK and 199 (27.8%)
      from Australia. The prevalence of analgesia provision declined across the three
      different time phases for spaying and castration (both p<0.001). Provision of
      analgesia for castration was less than for spaying at each of the pre/intra
      operative (p=0.002), post-operative (p<0.001) and after discharge (p<0.001)
      phases. Post-operative provision of analgesia following both castration (p<0.001)
      and spaying (p<0.001) differed amongst countries of practice. Veterinarians in
      Australia and New Zealand were more likely to provide post-operative analgesia
      for both castration and spaying than those from the UK (p<0.001). Veterinarians
      from the UK more commonly used non-steroidal anti-inflammatory drugs (NSAID) in
      the pre/intra-operative phase (p<0.001) than veterinarians from either New
      Zealand or Australia. CONCLUSIONS AND CLINICAL RELEVANCE: Contemporary use of
      analgesics for cats appears focused on provision at clinic and may not address
      the effects of surgery beyond the first 24 hours. The UK, Australia and New
      Zealand clearly differ in the types of analgesia administered, possibly
      reflecting differing professional considerations of the risks associated with the
      use of NSAID. In the interests of animal welfare, pain relief should perhaps be
      provided or offered more frequently for owner administration.

PMID- 24299562
TI  - A new package in MODFLOW to simulate unconfined groundwater flow in sloping
      aquifers.
AB  - The nonhorizontal-model-layer (NHML) grid system is more accurate than the
      horizontal-model-layer grid system to describe groundwater flow in an unconfined
      sloping aquifer on the basis of MODFLOW-2000. However, the finite-difference
      scheme of NHML was based on the Dupuit-Forchheimer assumption that the
      streamlines were horizontal, which was acceptable for slope less than 0.10. In
      this study, we presented a new finite-difference scheme of NHML based on the
      Boussinesq assumption and developed a new package SLOPE which was incorporated
      into MODFLOW-2000 to become the MODFLOW-SP model. The accuracy of MODFLOW-SP was
      tested against solution of Mac Cormack (1969). The differences between the
      solutions of MODFLOW-2000 and MODFLOW-SP were nearly negligible when the slope
      was less than 0.27, and they were noticeable during the transient flow stage and
      vanished in steady state when the slope increased above 0.27. We established a
      model considering the vertical flow using COMSOL Multiphysics to test the
      robustness of constrains used in MODFLOW-SP. The results showed that streamlines
      quickly became parallel with the aquifer base except in the narrow regions near
      the boundaries when the initial flow was not parallel to the aquifer base.
      MODFLOW-SP can be used to predict the hydraulic head of an unconfined aquifer
      along the profile perpendicular to the aquifer base when the slope was smaller
      than 0.50. The errors associated with constrains used in MODFLOW-SP were small
      but noticeable when the slope increased to 0.75, and became significant for the
      slope of 1.0. 

PMID- 24299561
TI  - Integrated molecular portrait of non-small cell lung cancers.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths,
      represents a heterogeneous group of neoplasms, mostly comprising squamous cell
      carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The
      objectives of this study were to utilize integrated genomic data including copy
      number alteration, mRNA, microRNA expression and candidate-gene full sequencing
      data to characterize the molecular distinctions between AC and SCC. METHODS:
      Comparative genomic hybridization followed by mutational analysis, gene
      expression and miRNA microarray profiling were performed on 123 paired tumor and
      non-tumor tissue samples from patients with NSCLC. RESULTS: At DNA, mRNA and
      miRNA levels we could identify molecular markers that discriminated significantly
      between the various histopathological entities of NSCLC. We identified 34 genomic
      clusters using aCGH data; several genes exhibited a different profile of
      aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes.
      Gene expression profiling analysis identified SPP1, CTHRC1 and GREM1 as potential
      biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish
      between AC and SCC in small biopsies or in blood samples. Using integrated
      genomics approach we found in recurrently altered regions a list of three
      potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over
      expressed in amplified regions, had wide-spread correlation with an average of
      ~800 genes throughout the genome and highly associated with histological types.
      Using a network enrichment analysis, the targets of these potential drivers were
      seen to be involved in DNA replication, cell cycle, mismatch repair, p53
      signalling pathway and other lung cancer related signalling pathways, and many
      immunological pathways. Furthermore, we also identified one potential driver
      miRNA hsa-miR-944. CONCLUSIONS: Integrated molecular characterization of AC and
      SCC helped identify clinically relevant markers and potential drivers, which are
      recurrent and stable changes at DNA level that have functional implications at
      RNA level and have strong association with histological subtypes.

PMID- 24299563
TI  - Quantitation of tumour development correlates with prognosis in tumour stage
      (stage IIB) mycosis fungoides.
AB  - BACKGROUND: Patients with mycosis fungoides (MF) tumour stage IIB disease show
      considerable variation in the number of tumours and time interval between each
      tumour occasion. OBJECTIVES: To quantify the extent of tumour formation in
      patients with stage IIB MF and correlation with survival. METHODS: The
      variability in tumour development of 46 patients with stage IIB MF was quantified
      by calculating a frailty score with the use of a statistical frailty model, based
      on both the number of tumours developed during follow-up and the time interval
      between each tumour occasion. The prognostic value of the frailty scores and the
      number of tumours at 6 and 12 months after first tumour development were studied.
      RESULTS: Frailty scores varied between 0.05 and 6.94. Patients with high
      frailties (> 1.0, n = 14) had the worst disease-specific survival (DSS) and
      overall survival (OS), compared with patients in the low frailty group (0-0.35, n
      = 17) and medium frailty group (0.35-1.0, n = 15). Differences in DSS and OS
      between the three frailty groups were highly significant (both P < 0.001). The
      number of tumours that developed within 6 months after the diagnosis of MF stage
      IIB was prognostic for subsequent DSS and OS (P < 0.001 and P = 0.021,
      respectively). CONCLUSIONS: The number of tumours and time interval between
      tumour formation differs greatly among patients with stage IIB MF and these
      differences correlate with survival. Patients with an adverse prognosis can be
      identified by quantifying the number of tumours that develop within 6 months
      after diagnosis of MF stage IIB.

PMID- 24299564
TI  - Abnormality of autophagic function and cathepsin expression in the liver from
      patients with non-alcoholic fatty liver disease.
AB  - AIM: Recent evidences indicate that hepatic steatosis suppresses autophagic
      proteolysis. The present study evaluated the correlation between autophagic
      function and cathepsin expression in the liver from patients with non-alcoholic
      fatty liver disease (NAFLD). METHODS: Liver biopsy specimens were obtained from
      patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic
      hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n =
      22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was
      counted by using transmission electron microscopy. Expression of cathepsin B, D,
      L and p62 in the liver section was analyzed by immunohistochemical staining. The
      histological severity of NAFLD is assessed by NAFLD activity score (NAS).
      RESULTS: The number of autophagic vesicles in hepatocytes was significantly
      increased in both CHC and NAFLD groups, but not CHB and PBC, more than control.
      Although hepatocytes with aggregation of p62 were observed in less than 15% of
      CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D
      and L expression was significantly suppressed in the liver from NAFLD patients.
      Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and
      PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine
      aminotransferase value and inflammatory activity by NAS. CONCLUSION: These
      results indicate that a decrease in hepatic cathepsin expression in NAFLD is
      associated with autophagic dysfunction. Hepatic inflammation correlates with
      autophagic dysfunction in NAFLD. These findings indicate that the suppression of
      autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of
      NAFLD.

PMID- 24299565
TI  - Modulation of mucosal/systemic antibody response after sublingual immunotherapy
      in mite-allergic children.
AB  - BACKGROUND: There have been no data on sublingual immunotherapy (SLIT) in
      Brazilian patients sensitized to house dust mites. This study aimed to evaluate
      the mucosal/systemic antibody response changes and clinical efficacy after SLIT
      using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial
      extracts in mite-allergic Brazilian children. METHODS: Patients with allergic
      rhinitis and asthma were selected for a double-blind, placebo-controlled trial
      randomized to three groups: DPT (Dpt extract, n = 34), DPT+MRB (Dpt plus mixed
      respiratory bacterial extracts, n = 36), and Placebo (n = 32). Total symptom and
      medication scores for rhinitis/asthma, skin prick test (SPT) to Dpt, and
      measurements of Dpt-, Der p 1-, Der p 2-specific serum IgE, IgG4, IgG1, and
      specific salivary IgA were evaluated at baseline and after 12 and 18 months of
      treatment. RESULTS: A significant long-term decline in total symptom/medication
      scores was observed only in active groups (DTP and DPT+MRB). There was no
      significant change in SPT results in all groups. SLIT using Dpt allergen alone
      induced increased levels of serum IgG4 to Dpt, Der p 1, and Der p 2, serum IgG1
      and salivary IgA to Dpt and Der p 1. SLIT with Dpt plus bacterial extracts was
      able to decrease IgE levels, particularly to Der p 2, to increase salivary IgA
      levels to Der p 1, but had no changes on specific IgG4 and IgG1 levels.
      CONCLUSIONS: All children undergoing SLIT showed clinical improvement, but a long
      term reduction in symptom/medication scores with modulation of mucosal/systemic
      antibody responses were seen only in active groups (DPT and DPT+MRB).

PMID- 24299566
TI  - Improving operating theatre communication between the orthopaedics surgeon and
      radiographer.
AB  - OBJECTIVES: This study was designed to assess the importance of communication
      between surgeons and radiographers in the operation of image intensifiers during
      orthopaedic surgery. METHODS: This study was designed and conducted as single
      centre, observational study. Fifteen medical officers and 15 radiographers were
      involved in this study. Each of the 15 radiographers was assigned to a medical
      officer. The 15 pairs were then each given a task to simulate achieving 'perfect
      circles' on fluoroscopy for distal locking of an intramedullary nail. The time
      taken for the surgeon to verbally instruct the radiographer how to position the
      image intensifier in order to achieve 'perfect circles' was recorded. The overall
      time taken to perform the task, and total number of images taken was recorded
      before and after a terminology system to manoeuvre image intensifier was
      introduced to the pairs. RESULTS: The mean time taken for the pairs to achieve
      perfect circles after the introduction of the manoeuvre terminology showed
      statistically significant reduction from 212 to 97 s (t = 4.212, df = 88, P <
      0.05) after the introduction of the terminology. The mean number of fluoroscopy
      exposures taken also showed a statistically significant reduction from 12 to 6 (t
      = 6.791, df = 88, P < 0.05). CONCLUSION: The implementation of a clear and
      unambiguous set of commands to control the image intensifier, which are common to
      both surgeon and radiographer, can reduce the time to acquire the desired images,
      and requires less radiation exposure in the process.

PMID- 24299567
TI  - Kadcotriones A-C: tricyclic triterpenoids from Kadsura coccinea.
AB  - Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically
      related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea.
      Compound 1 features a 12,14beta-dimethyl 6/6/6-fused tricyclic skeleton, while 2
      and 3 are characterized by a 6/6/5-ring system. Their structures were determined
      by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4
      exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 MUM,
      respectively. 

PMID- 24299569
TI  - Effects of multiple sclerosis on female sexuality: a controlled study.
AB  - AIM: The aim of this study was to investigate the effects of multiple sclerosis
      (MS) on female sexuality. METHODS: Present study included 142 females (70 MS
      patients, 72 healthy controls). MS patients were evaluated by Expanded Disability
      Status Scale (EDSS) for functional status, by Beck Depression Inventory (BDI) for
      severity of depression, by Visual Analog Scale (VAS) for severity of pain, and by
      Female Sexual Function Inventory (FSFI) for sexual function. MAIN OUTCOME
      MEASURES: FSFI, BDI, EDSS, and VAS were the main outcome measures. RESULTS: The
      number of weekly sexual intercourse, total FSFI, and FSFI subscale scores were
      lower in MS women compared with controls. FSFI total and FSFI subscale scores
      were statistically significantly lower in MS women with BDI score >= 17 compared
      with those with BDI score <17. A negative correlation was found between total
      FSFI score and BDI, EDSS, VAS, age, and duration of complaint, but a positive
      correlation was found with education level in MS women. CONCLUSIONS: Sexual
      functions are negatively affected in MS women. Sexual functions in MS women seem
      to be associated with enhanced disability, pain, duration of the disease, and
      degree of concomitant depression. Therefore, women with MS should also be
      evaluated in terms of sexual function during routine follow-ups.

PMID- 24299568
TI  - The H1N1 pandemic: media frames, stigmatization and coping.
AB  - BACKGROUND: Throughout history, people have soothed their fear of disease
      outbreaks by searching for someone to blame. Such was the case with the April
      2009 H1N1 flu outbreak. Mexicans and other Latinos living in the US were quickly
      stigmatized by non-Latinos as carriers of the virus, partly because of news
      reports on the outbreak's alleged origin in Mexican pig farms. METHODS: In this
      exploratory study we examined the psychological processes of cue convergence and
      associative priming, through which many people likely conflated news of the H1N1
      outbreak with pre-existing cognitive scripts that blamed Latino immigrants for a
      variety of social problems. We also used a transactional model of stress and
      coping to analyze the transcripts from five focus groups, in order to examine the
      ways in which a diverse collection of New England residents appraised the threat
      of H1N1, processed information about stereotypes and stigmas, and devised
      personal strategies to cope with these stressors. RESULTS: Twelve themes emerged
      in the final wave of coding, with most of them appearing at distinctive points in
      the stress and coping trajectories of focus group participants. Primary and
      secondary appraisals were mostly stressful or negative, with participants born in
      the USA reporting more stressful responses than those who were not. Latino
      participants reported no stressful primary appraisals, but spoke much more often
      than Whites or Non-Hispanic Blacks about negative secondary appraisals. When
      interactions between participants dealt with stigmas regarding Latinos and H1N1,
      Latinos in our focus groups reported using far more negative coping strategies
      than Whites or Non-Hispanic Blacks. When discussions did not focus on stereotypes
      or stigmas, Latino participants spoke much more often about positive coping
      strategies compared to members of these same groups. CONCLUSIONS: Participants in
      all five focus groups went through a similar process of stress and coping in
      response to the threat of H1N1, though individual responses varied by race and
      ethnicity. Stigmatization has often been common during pandemics, and public
      health and emergency preparedness practitioners can help to mitigate its impacts
      by developing interventions to address the social stressors that occur during
      outbreaks in highly-localized geographic regions.

PMID- 24299570
TI  - Light-harvesting polymers: ultrafast energy transfer in polystyrene-based arrays
      of pi-conjugated chromophores.
AB  - Energy transfer along a nonconjugated polymer chain is studied with a polystyrene
      based copolymer of oligo(phenylene-ethynylene) (OPE) donor and thiophene
      benzothiadiazole (TBT) acceptor pendants. The graft copolymers are prepared from
      reversible addition-fragmentation transfer polymerization (RAFT) and copper(I)
      catalyzed azide-alkyne "click" reaction. The singlet energy transfer from donor
      to accept is studied via fluorescence emission and ultrafast transient absorption
      spectroscopy. Near unity quenching of the OPE excited state by the TBT moiety
      occurs on multiple time scales (2-50 ps) dependent on where the initial exciton
      is formed on the polymer. 

PMID- 24299571
TI  - Intralesional treatment for keloids and hypertrophic scars: a review.
AB  - BACKGROUND: Although differing in clinical presentation and prognosis, keloids
      and hypertrophic scars are generally characterized by abnormally proliferative
      scar tissue and are extremely debilitating. Several intralesional therapies have
      been studied in attempts to find a universally safe and effective modality, of
      which there are currently none. OBJECTIVE: To provide a comprehensive review of
      current intralesional treatment modalities for keloids and hypertrophic scars.
      METHODS AND MATERIALS: A PubMed search was performed for literature pertaining to
      intralesional treatment modalities for keloids and hypertrophic scars. References
      from retrieved articles were also considered for review. RESULTS AND CONCLUSION:
      Many intralesional therapies for keloids and hypertrophic scars are currently
      available to physicians and patients. Mechanisms of action and side effect
      profiles vary between these agents, and new approaches to keloids and
      hypertrophic scars are frequently being explored. Randomized controlled trials
      are needed to assess these new and promising modalities fully.

PMID- 24299572
TI  - Efficacy of photodynamic diagnosis-guided Mohs micrographic surgery in primary
      squamous cell carcinoma.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) usually has ill-defined
      margins because of its irregular invasive patterns. OBJECTIVE: To evaluate the
      surgical efficacy of photodynamic diagnosis (PDD) in primary cSCC treated using
      Mohs micrographic surgery (MMS). METHODS & MATERIALS: We examined 67 cases of
      biopsy-proven primary facial cSCC treated with MMS. The 67 SCC were divided into
      the two groups depending on PDD application: PDD group (n = 38, 56.7%) and non
      PDD group (n = 29, 43.3%). We analyzed the differences in surgical features
      between the PDD and non-PDD groups. RESULTS: The PDD group required fewer Mohs
      stages (1.37 vs 1.83, p = .02) and smaller surgical margins (8.03 vs 11.24 mm, p
      = .03). PDD showed additional benefits in terms of surgical margin and Mohs
      stage, especially in low-risk SCC, including thin (<=4 mm), small (<=20 mm), well
      differentiated, and nonulcerative tumors (p < .05) but did not show beneficial
      effects in high-risk SCC (p > .05) during MMS. CONCLUSION: PDD can increase
      surgical efficacy of primary cSCC during MMS. These benefits are more pronounced
      in low-risk SCC. We recommend PDD as a simple and useful technique for
      delineating the margins of low-risk SCC before MMS.

PMID- 24299573
TI  - Prognostic value of sentinel lymph node biopsy compared with that of Breslow
      thickness: implications for informed consent in patients with invasive melanoma.
AB  - BACKGROUND: Sentinel lymph node (SLN) status is reportedly a powerful
      prognosticator of survival. Breslow thickness alone provides significant
      prognostic information. OBJECTIVE: To assess overall survival (OS) according to
      tumor depth based on SLN status. MATERIALS AND METHODS: MEDLINE, EMBASE, and the
      Cochrane Central Database were searched for studies. Included studies evaluated
      overall survival according to SLNB results and were stratified according to
      Breslow thickness. Meta-analysis was performed if appropriate in each category
      for which three or more studies reported risk estimates and variability
      measurement. RESULTS: Twenty-nine articles met inclusion criteria. Six met the
      criteria for meta-analysis. In individuals with thin melanoma (<1 mm), SLN
      negative status conferred no survival advantage (sign test, p > .99). Few studies
      were available for intermediate depths, and most reported worse survival in SLN
      positive patients, although the difference was not statistically significant (p >
      .05). For thick melanoma (>4 mm), SLN positivity was related to worse prognosis
      (sign test, p = .004). Based on the pooled results of six studies of patients
      with tumors 4 mm thick or thicker, SLN-positive patients had a greater likelihood
      of dying (hazard ratio = 2.42, 95% confidence interval = 2.00-2.92). CONCLUSIONS:
      Sentinel lymph node biopsy may not provide more-accurate prognostic information
      than Breslow thickness for most melanomas.

PMID- 24299574
TI  - Appropriate timing for thyroidectomy scar treatment using a 1,550-nm fractional
      erbium-glass laser.
AB  - BACKGROUND: Surgical scarring is a common cosmetic problem that occurs in various
      surgical fields, including dermatology. Many trials have been conducted to
      determine how to prevent this distressing scar formation. A 1,550-nm fractional
      erbium-glass laser has been used to improve the appearance of surgical scars, but
      an appropriate treatment time has not been established. OBJECTIVES: To determine
      the appropriate time to apply 1,550-nm fractional erbium-glass laser treatment
      for thyroidectomy scars. MATERIALS AND METHODS: Korean patients with linear
      surgical suture lines after thyroidectomy (N = 65) were treated using a 1,550-nm
      fractional erbium-glass laser. Patients were divided into three groups according
      to postoperative treatment time. Laser treatment was started in 40, 15, and 10
      patients 3 weeks, 3 months, and 6 months postoperatively, respectively. Each
      patient was treated three times at 1-month intervals using the same parameters
      (14 mJ, 100 spots/cm(2) , 2 passes). RESULTS: Mean Vancouver Scar Scale scores
      were significantly lower after laser treatment (p < .01), with the greatest
      difference in the group that began treatment 3 weeks postoperatively. Global
      assessment also indicated better cosmetic outcomes in the 3-week postoperative
      treatment group. CONCLUSION: Early postoperative 1,550-nm fractional erbium-glass
      laser treatment of thyroidectomy scars is more effective than later treatment.

PMID- 24299575
TI  - Commentary: Asian consensus recommendations on the aesthetic usage of botulinum
      toxin type A.

PMID- 24299576
TI  - Safety and efficacy of one-step rehabilitation of human immunodeficiency virus
      related facial lipoatrophy using an injectable calcium hydroxylapatite dermal
      filler.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-related facial lipoatrophy seems
      to be the most distressing manifestation for individuals with HIV. It can be
      stigmatizing, severely affecting quality of life and self-esteem. Ever-increasing
      numbers of individuals with HIV receiving medication for HIV infection are
      presenting to plastic surgeons and requesting reconstructive surgery to
      counteract the unwanted side effects of their treatment protocols, for example
      facial lipoatrophy. The authors show their results with a one-step rehabilitation
      in cases of facial lipoatrophy using an injectable calcium hydroxylapatite dermal
      filler mixed with local anesthetic and adrenaline. MATERIALS AND METHODS: This
      study was conducted as a clinical prospective study; 26 individuals with HIV
      receiving antiretroviral therapy and with facial lipoatrophy received injections
      of an injectable calcium hydroxylapatite dermal filler mixed with local
      anesthetic and adrenaline. RESULTS: No major complications were registered. A
      stable result was observed in all the cases at the end of follow-up (3 months).
      High patient satisfaction was achieved in all cases. CONCLUSION: The outcomes of
      this study confirm that calcium hydroxylapatite dermal filler safely and
      effectively ameliorates the appearance of patients with HIV-related facial
      lipoatrophy, and mixing it with local anaesthetic and adrenaline can reduce pain
      during injection and ecchymosis.

PMID- 24299577
TI  - Successful treatment of a pseudocyst of the auricle using intralesional sodium
      tetradecyl sulfate injection.

PMID- 24299578
TI  - Medicine and nursing: a social contract to improve collaboration and patient
      centred care?

PMID- 24299579
TI  - An Australian hospital-based student training ward delivering safe, client
      centred care while developing students' interprofessional practice capabilities.
AB  - Royal Perth Hospital, in partnership with Curtin University, established the
      first interprofessional student training ward in Australia, based on best
      practice from Europe. Evaluation of the student and client experience was
      undertaken. Feedback from all stakeholders was obtained regularly as a key
      element of the quality improvement process. An interprofessional practice program
      was established with six beds within a general medical ward. This provided the
      setting for 2- to 3-week clinical placements for students from medicine, nursing,
      physiotherapy, occupational therapy, social work, pharmacy, dietetics and medical
      imaging. Following an initial trial, the training ward began with 79 students
      completing a placement. An interprofessional capability framework focused on the
      delivery of high quality client care and effective teamwork underpins this
      learning experience. Quantitative outcome data showed not only an improvement in
      students' attitudes towards interprofessional collaboration but also acquisition
      of a high level of interprofessional practice capabilities. Qualitative outcome
      data from students and clients was overwhelmingly positive. Suggestions for
      improvement were identified. This innovative learning environment facilitated the
      development of the students' knowledge, skills and attitudes required for
      interprofessional, client centred collaborative practice. Staff reported a high
      level of compliance with clinical safety and quality.

PMID- 24299581
TI  - Review of the accumulated PLATO documentation supports reliable and consistent
      superiority of ticagrelor over clopidogrel in patients with acute coronary
      syndrome: Commentary on: DiNicolantonio JJ, Tomek A, Inactivations, deletions,
      non-adjudications, and downgrades of clinical endpoints on ticagrelor: serious
      concerns over the reliability of the PLATO trial, International Journal of
      Cardiology, 2013.

PMID- 24299582
TI  - MRI disturbances caused by dental materials.
AB  - Dental materials are common sources of artifacts during brain MRI studies. The
      aim of the present study was to estimate the degree of image disturbance caused
      by dental materials during an MRI examination, and the risk of ferromagnetic
      materials being dislocated in the magnetic field. MR sequences where dental
      materials containing metals produced the smallest artifacts was also calculated.
      Thirty-five dental material samples containing metals were examined using the 1.5
      T MR system. They consisted of the most commonly used dental restorations and
      root-canal instruments left in the oral cavity for iatrogenic reasons.
      Additionally, cubes (10*5*5 mm) and balls (10 mm diameter) were cast from
      commonly used dental alloys. No dislocation of the examined samples in the
      gelatin medium was observed. All the materials were found to produce artifacts
      characterised by similar images. The study showed that the presence of distant
      artifacts, besides those located in the area immediately surrounding the object,
      depends on the shape of the given material. The size of artifacts generated by
      the most commonly used fixed restorations was graded. The sequences in which
      artifacts were least pronounced were selected. No dislocation of samples in the
      1.5 T field was observed during the examination. However they produced artifacts;
      the typical image of an artifact - a signal void zone surrounded by a
      hyperintensive rim. Alloys consisting of Ag-Pd, dental gold and amalgam distorted
      the MR image to the least degree. In the case of a routine spin echo (SE)
      sequence examination the smallest artifacts were generated in the FSE T2 and PD
      sequences. 

PMID- 24299583
TI  - Measuring anisotropic brain diffusion in three and six directions: influence of
      the off-diagonal tensor elements.
AB  - Diffusion tensor imaging (DTI) has been proposed for examination of cerebral
      white matter. However, this measurement needs sophisticated postprocessing and is
      susceptible to eddy current artefacts. The aim of this study was to examine
      whether diffusion measured in three anatomically well defined directions provides
      full and reliable information on diffusion anisotropy. Measurements were
      performed in water and gelatine phantoms and in 14 healthy volunteers. Diffusion
      was measured in six independent directions. For the full tensor DTI we
      diagonalised the diffusion tensor, for measurements with three directions we used
      only the diagonal elements. We then calculated the diffusion trace and the linear
      anisotropy index (AIl). We measured a slight anisotropy in the phantoms, which
      was larger in the case of the full tensor DTI (AIl = 0.022) then for the three
      orthogonal diffusion directions (0.008-0.019). The linear anisotropy index
      measured in white matter regions within the right and left hemisphere ranged
      between 0.33 and 0.42. AIl values were moderately correlated between right and
      left hemisphere regions (correlation factor: 0.35-0.64). DTI using the full
      tensor information is more susceptible to systematic errors resulting from eddy
      current effects than the measurement of diffusion in three orthogonal directions.
      However, in the latter method the anisotropy index is systematically
      underestimated in anatomical structures that do not exhibit a principal diffusion
      parallel to one of the diffusion directions. Therefore it is recommended to use
      the full tensor method together with sophisticated methods for eddy current
      correction. 

PMID- 24299584
TI  - Bilateral internal carotid artery segmental agenesis associated with persistent
      trigeminal artery, vascular ectasia, abnormal configuration of brain stem and
      cerebellum. A case report.
AB  - Bilateral segmental agenesis of the internal carotid artery is a rare
      developmental anomaly. We report a case of congenital bilateral internal carotid
      arteries segmental agenesis associated with persistent trigeminal artery,
      vascular ectasia and abnormal configuration brain stem and cerebellum. We
      postulate that these findings could result from interference in development
      during the early stages. 

PMID- 24299585
TI  - Intracranial lipomas: a retrospective study.
AB  - Between 1996 and 2006, 17 patients with intracranial lipomas underwent MR imaging
      examination. Of these, two patients also had CT examination. Lipoma is not a
      typical tumor and could instead be called intracranial lipoma hamartoma or
      cerebral malformation. The predominant localization of the lipomas was close to
      midline structures, such as the area around the corpus callosum, quadrigeminal
      cisterns, etc. Interpreting the MRI it is necessary to differentiate epidermoid,
      dermoid and hemorrhage in the metahemoglobin stage from lipoma. Clinically, 47%
      of patients complained of headache, two presented with epileptic seizures and the
      remainder had different symptoms. The lipoma was just an incidental finding not
      related to the clinical symptomatology. 

PMID- 24299586
TI  - Diffuse Cerebral Cortex, Cerebellar Cortex and Basal Ganglia Injury: a Rare MR
      Imaging Manifestation of Heat Stroke.
AB  - We present a case of heat stroke with rare magnetic resonance (MR) imaging
      manifestations. In addition to abnormal high signals in bilateral cerebellum and
      basal ganglia seen on T2-weighted MR images (T2WI), the case showed diffuse
      cerebral cortical high signals on T2WI and diffusion-weighted images (DWI). Heat
      stroke with diffuse hypoperfusion to the brain due to diversion of blood
      circulation was hypothesized as the cause of brain injury, including the cerebral
      cortex. 

PMID- 24299587
TI  - 'Torch Fire Sign': a New MR Sign in Profound Hypoxic Ischemic Brain Injury in a
      Term Infant.
AB  - Hypoxic-ischemic injury can produce diverse patterns of brain damage detected on
      MR imaging which mainly depend on the severity of brain ischemia and the maturity
      of the brain at the time of insult (1). In a term infant severe ischemia produces
      maximum damage in the lateral thalami, posteromedial putamen, hippocampi and the
      dorsal brain stem in addition to the perirolandic cortex (2). This is because
      these areas are the most metabolically active sites in the neonate (3). 

PMID- 24299588
TI  - Atypical Clinical Picture in a Patient with Benign Occipital Epilepsy: Diagnostic
      Contribution of Morpho-Functional MR. A Case Report.
AB  - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS) is a maternally inherited disease due to mitochondrial DNA (mtDNA) point
      mutations. The clinical phenotype varies in relation to the systems affected, age
      at onset and disease severity. The characteristic signs of MELAS are nausea and
      vomiting due to acidosis, headache, epilepsy, ataxia or generalized weakness,
      ophthalmoplegia, motor and sensory focal neurological deficits. The clinical
      course may improve due to partial regression of the typical lesions, but the
      prognosis is usually adverse. A 19-year-old man with a diagnosis of benign
      occipital epilepsy and resumption of seizure activity with focal occipital
      attacks since the age of 14 years came to our attention for the recent onset of
      drug-resistant electroclinical seizures of long duration with complex symptoms,
      where the dominant clinical feature was an intense, persistent bilateral
      periorbital migraine with nausea and vomiting, scintillation scotomata and
      blurring of vision. MR studies were performed at our institution in the immediate
      post-seizure phase and then at one week, three and six months. The acute-phase
      morphological scans showed a right cortical-subcortical area with altered signal
      in the occipitopolar region that was hypointense on T1 and hyperintense on T2 and
      FLAIR, with cortical thickening and effacement of the sulci. Contrast-enhanced
      scans did not demonstrate BBB alterations. The DWI scans showed a right temporo
      occipital cortical area with higher signal intensity. In the subsequent
      examinations the area with altered signal shrank gradually and significantly in
      parallel with improvement in clinical conditions. The diagnostic hypothesis of
      benign occipital epilepsy was consistent neither with the clinical course,
      characterized by persistent headache, visual disturbance and refractoriness to
      antiepileptic drugs, nor with the temporal-occipital cortical MR findings, which
      resembled ischemic lesions but displayed a non-territorial pattern as well as
      reversibility over time. These elements guided in the diagnosis of MELAS, which
      was subsequently confirmed by identification of the typical gene mutation. On DWI
      the stroke-like lesions of MELAS are seen more frequently as focal hyperintense
      areas compared with healthy parenchyma. Such high signal intensity likely
      corresponds to T2 shine-through rather than cytotoxic edema. Indeed, several
      studies have demonstrated that in acute-phase scans of MELAS stroke-like lesions
      DWI hyperintensity is associated with increased ADC values that are not
      associated with restricted water diffusivity, reflecting the metabolic rather
      than anoxic-ischemic nature of these changes. In the present case, morphological
      MR associated with DWI was very helpful in guiding the diagnosis by demonstrating
      some pathognomonic features of MELAS stroke-like lesions such as cortical
      subcortical involvement of the posterior hemispheres, the non-territorial
      pattern, lesion reversibility and the pathophysiological role of vasogenic edema
      in inducing an increase in extracellular water and thus in diffusion values. 

PMID- 24299589
TI  - Leigh Syndrome: an MR Study of Three Cases.
AB  - Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is the most
      common childhood mitochondrial encephalopathy, accounting for more than 50% of
      cases in this age group. Its estimated incidence is 1:40,000 - 1:77,000 liveborn
      infants a year. LS is a rare progressive multisystem fatal disorder inherited by
      autosomal recessive, X-linked and maternal transmission. Clinical onset is
      predominantly in the first two years of life (average: six months); 50% of
      patients die within a year, even though there are later- and even adult-onset
      forms with a more protracted evolution. LS is due to a deficit of various
      respiratory chain and Krebs cycle enzymes resulting in insufficient production of
      adenosine triphosphate (ATP), in particular cytochrome-c-oxidase (COX), pyruvate
      carboxylase, pyruvate dehydrogenase complex and complex I of the respiratory
      chain, which share an autosomal recessive and X-linked mode of transmission.
      Cases with maternal inheritance (MILS) are due to a mitochondrial DNA (mtDNA)
      point mutation. LS is clinically heterogeneous in relation to the severity of the
      metabolic dysfunction and is characterized by muscle involvement and especially
      CNS disorders, particularly psychomotor retardation, ocular symptoms, hypotonia
      and pyramidal signs. Death is most commonly due to respiratory failure, status
      epilepticus and sudden coma. The major neuropathological findings, first
      described by Leigh in 1951, are symmetrical foci of spongy necrosis associated
      with vessel proliferation and reactive gliosis in basal nuclei, brainstem and
      thalamus grey matter. The neuronal metabolic alteration can also affect the white
      matter, resulting in delayed myelination or hypomyelination. The diagnosis rests
      on clinical signs, elevated CSF lactate, pyruvate and alanine, and biochemical
      and neuroradiological data. We describe two patients with LS studied with
      morphological MR associated with diffusion and spectroscopy techniques to assess
      the diagnostic potential of standard MR imaging and establish whether the
      association of functional MR methods can improve its diagnostic accuracy. A case
      of LS with a post-mortem MR study is also described. Three patients with a
      diagnosis of LS based on clinical, CSF and laboratory data were studied on a GE
      SIGNA EXCITE 1.5 T unit using an eight-channel phased-array head coil to acquire
      standard sequences (SE T1; TSE DP T2; FLAIR) and echo-planar diffusion-weighted
      sequences (DWI; b= 1000 s/mm2) with calculation of ADC maps. The spectroscopic
      study used single-voxel (TE/TR ms = 144/1500) and multi-voxel techniques (TE/TR
      ms = 144/1000) at the level of the basal nuclei. Bilateral and symmetrical
      involvement of basal nuclei grey matter with T2 hyperintensity was a consistent
      finding in the morphological MR study. In one patient, associated white matter
      involvement with T2 hyperintensity in periventricular and retrotrigonal areas
      reflected delayed myelination or hypomyelination. The deep grey matter changes,
      sometimes associated with white matter lesions, suggested a diagnosis of subacute
      necrotizing encephalomyelopathy, in line with the literature. Acute-phase ADC
      values in affected areas were lower than those of normal grey and white matter
      and displayed signal hyperintensity on DWI. Reduced ADC values are associated
      with restricted water diffusivity typical of cytotoxic edema. Spectroscopy showed
      a high lactate peak, reflecting altered anaerobic glycolysis, and a reduced NAA
      peak in affected areas, which are however non-specific findings. The most
      informative study in these patients is standard MR associated with functional
      techniques, which can confirm the diagnosis obtained with morphological imaging. 

PMID- 24299590
TI  - Emerging patterns of diffusion, perfusion-weighted MRI and spectroscopy in
      creutzfeldt-jacob disease.
AB  - Sporadic Creutzfeldt-Jacob disease (CJD) is a transmissible, progressive, fatal
      spongiform encephalopathy. Routine MR imaging sequences may show abnormalities in
      the basal ganglia and cerebral cortex. Recently, several reports claimed that
      diffusion weighted MRI (DWI) could demonstrate early brain lesions in CJD
      patients when conventional MR images are normal on T2-weighted sequences. We
      evaluated the usefulness of DWI, perfusion-weighted MRI (PWI) and spectroscopy to
      confirm the clinical diagnosis and assess lesion progression in two patients with
      suspected CJD. We noted a diffuse hypoperfusion in the basal ganglia where ADC
      values were reduced but spectroscopy values were normal. A strong hypoperfusion
      was observed in the right head of the caudate nucleus in patient n degrees  2
      where spectroscopy values were abnormal. A typical distribution of hypoperfusion
      followed the posterior progression of disease. We suggest the hypoperfusion in
      the areas presenting restricted diffusion probably reflects spongiform
      degeneration and moderate mass effects from cytotoxic edema. 

PMID- 24299591
TI  - Central neurocytoma: case report of an 81-year-old and histopathologic findings.
AB  - Central Neurocytomas are rare and usually benign tumors found primarily in the
      lateral ventricles of the brain. Central Neurocytomas are composed of uniform
      round cells exhibiting neuronal differentiation and are found almost exclusively
      in young adults between 15 and 60 years of age. The authors report the case of an
      81-year-old man with a history of severe psychosis and depression, who presented
      with progressive confusion and ataxia likely unrelated to a central neurocytoma
      of his right lateral ventricle. The patient underwent a stereotactic biopsy of
      the lesion, followed by Gamma Knife radiosurgery. Histopathology showed
      immunohistological staining for synaptophysin, neuron specific enolase (NSE) and
      neuronal nuclear antigen (NeuN). A review of published literature on central
      neurocytomas revealed that this tumor occurs most frequently in young adults with
      a median age between 25 and 30 years. This pathology has never been reported in
      patients over the age of 80. Gamma Knife radiosurgery was successful in
      decreasing the tumor volume by 20% at the four month follow-up, but the fact that
      the patient died of unrelated occurrences in the elderly cannot be ruled out.
      Patients with central neurocytomas commonly present with obstructive
      hydrocephalus and immediate treatment may be necessary to tide over urgent
      situations. 

PMID- 24299592
TI  - Three-dimensional computer reconstruction of a fourth ventricle ependymoma.
AB  - It is very important to establish the surgical strategy for fourth ventricle
      ependymoma with the aim of total tumor resection because improving the degree of
      surgical removal is the most promising means of improving outcome. We present our
      experience in reconstructing a three-dimensional (3-D) image of a fourth
      ventricle ependymoma perioperation. We used computer-assisted 3-D reconstruction
      to visualize a fourth ventricle ependymoma. Tumor outlines were manually traced
      out and imported to a 3-D visualization tool for 3-D reconstruction. The patient
      was operated through a median infratentorial approach. Perioperation by rotating
      the 3-D image and observing from various angles, we acquired abundant information
      such as 3-D tumor contour, the relation between the tumor and the wall of the
      fourth ventricle, the origin and invasion of the tumor, which were very useful to
      monitor tumor resection, adjust the approach to the ependymoma, and avoid
      inadvertent injury of important anatomic structures. Computer-assisted 3-D
      reconstruction may not only provide useful information before and during surgery,
      but also simplify the surgical procedure. It may be a useful aid to surgery
      making neurosurgery less invasive and more effective. 

PMID- 24299593
TI  - De novo Formation of the Ventriculus Terminalis? A Brief Report of a Special
      Case.
AB  - The ventriculus terminalis is an ependymal cystic cavity in the conus medullaris,
      sometimes found in children. Persistence of the ventriculus terminalis in adults
      can cause lower back pain or neurological disturbances. However, there are no
      literature reports of de novo formation of a ventriculus terminalis in the conus
      medulallaris, as in the case we illustrate here. 

PMID- 24299594
TI  - CT Perfusion in Spinal Disease: an Adjunct Tool to Vertebral Body Biopsy.
AB  - Routine diagnostic techniques are inadequate for diagnosis of spinal diseases.
      The purpose of this study was to determine whether CT perfusion can differentiate
      inflammatory diseases like tuberculosis from neoplastic diseases of spine. Thirty
      two patients with vertebral body lesions associated with paraspinal mass
      underwent CT guided bone biopsy and histopathological evaluation. CT perfusion
      was done in all patients before doing biopsy. Perfusion parameters like blood
      volume (BV), blood flow (BF) and time to peak (TTP) were calculated and
      correlated with histopathology. Statistical analysis was done using Mann-Whitney
      test. p value <0.05 was considered significant. Of 32 cases, 20 had tuberculous
      osteomyelitis and 12 neoplastic disease (seven metastasis, three plasmacytoma,
      one each lymphoma and chordoma). Mean rBF was [inflammatory lesions, 1.459 and
      neoplastic lesions, 18.080 (p<0.000). Mean rBV was (inflammatory disease, 2.8589
      and neoplastic lesions, 12.2133 (p<0 .000)). Mean rTTP was [inflammatory
      pathology, 1.041 and neoplastic pathology, 0.703(p<0.079)]. This shows the
      deconvolution-based CTP technique's potential for noninvasive diagnosis of at
      least all inflammatory lesions affecting the spine that are associated with
      paraspinal mass. Validation of the use of deconvolution CTP parameters for
      differentiation of inflammatory from neoplastic pathology may permit this
      technique to be used as an adjunct tool when biopsy when routine imaging findings
      are inconclusive. 

PMID- 24299595
TI  - Isolated unilateral sixth nerve palsy as a presenting symptom of cerebral
      aneurysms. Report of two cases.
AB  - We describe two patients with intracranial aneurysms who presented with isolated
      sixth nerve palsy. A 68-year-old woman with gradual onset of horizontal lateral
      diplopia was found to have a giant aneurysm at the junction of the petrous and
      cavernous portion of the internal carotid artery. A 58-year-old man presented
      with gradual onset of occipital pain followed by a sixth nerve palsy. He was
      found to have a distal anterior inferior cerebellar artery aneurysm which
      spontaneously thrombosed on subsequent neuroimaging studies. Although uncommon,
      isolated sixth nerve palsy can be the only neurological sign of an intracranial
      aneurysm. 

PMID- 24299596
TI  - Facial steal syndrome: identification and endovascular management.
AB  - We describe a case of intraprandial vertebro-basilar insufficiency secondary to
      posterior cerebral circulation ischemia. Secondary collateralization was seen
      from facial and external carotid artery branches to the posterior circulation
      causing facial arterial steal during mastication. This condition was treated
      endovascularly. Occluded common and external carotid arteries were revascularized
      via angioplasty and stenting. The patient was able to undergo coronary artery
      bypass and right hip replacement in the following two months without
      cerebrovascular complications. 

PMID- 24299597
TI  - Angiographic and clinical results after endovascular treatment for middle
      cerebral artery berry aneurysms.
AB  - Sixty-five middle cerebral artery (MCA) aneurysms in 59 patients treated by
      endovascular treatment (EVT) without the remodelling technique were analyzed. For
      ruptured aneurysms, the patients in bad condition are predominant and those with
      Fisher group four is 47.8% and with Hunt and Hess grade (HHG) IV or V are 43.5%.
      The clinical result is that 58.7% is in mRS 0-3, 21.7% in 4-5 and 19.6% in death.
      Contrary, 92.3% of the patients in HHG I-III resulted in mRS 0-3. Re-rupture was
      observed in two cases (4.4%). For all the aneurysms, thromboembolic complications
      were observed in 12.3% and those were predominant in the aneurysms greater than
      10mm in diameter (p<0.05). Hemorrhagic ones occurred in 6.2% which were
      predominant in the aneurysms less than 10mm in diameter. No mortality was
      observed by the accidents. In follow-up angiography, Raymond classification was
      employed and Complete Obliteration or Dog Ear was observed in 24 of 43 cases
      (55.8%). Recanalization occurred in 10.5% of the cases with complete or almost
      complete obliterated aneurysms. These results suggested that EVT for the ruptured
      MCA aneurysms with good grade or the unruptured ones is feasible. Strict follow
      up is important like the other aneurysms. 

PMID- 24299598
TI  - The Relationship between Carotid Artery Diameter and Percentage of Stenosis.
AB  - In order to understand percentage of stenosis from the residual lumen of the
      carotid artery, we explored the relationship between the residual diameter at the
      carotid stenosis, its stenosis percentage and the size of the internal carotid
      artery. Diameters of 103 carotid arteries of Taiwan residents were
      retrospectively measured from digital subtraction angiograms. Severe cases of
      near occlusion with the angiographic string sign, and cases with tandem lesions
      or intracranial occlusion were excluded. Of the total 103 carotid arteries, 22
      (21%) had one or both of the following signs of reduced distal arterial caliber:
      (1) obvious narrowing of the distal carotid artery; (2) the caliber of the
      cervical internal carotid artery was smaller than the caliber of the
      corresponding external carotid artery. That the diameter of the distal carotid
      artery was smaller when the stenosis was greater at the site of minimal lumen was
      true in the group of patients with signs of reduced distal caliber and in the
      group of patients without such signs. Therefore, reduced distal caliber may be
      present in patients without such signs. After excluding cases with at least one
      of the above signs of reduced distal arterial caliber, the relation between
      percentage of stenosis (y) and the absolute value of the diameter at the stenosis
      (x) can be represented by the formula: y = 96.83-18.27 x. From our data, a
      diameter of 2 mm is about 60% stenosis and 1.5 mm is 70% stenosis. According to
      this formula, we can estimate percentage of carotid stenosis using residual
      diameter at the site of minimal lumen obtained from other imaging modalities,
      such as carotid Doppler, CT angiogram or MR angiogram. 

PMID- 24299599
TI  - Protected carotid stenting: the usefulness of filter protection devices.
AB  - We report our experience in carotid artery stenting using a filter protection
      device. From July 2003 to September 2006 we treated 62 patients by internal
      carotid stenting using a filter protection device. Procedural success was
      achieved in 100% of cases. There were five periprocedural complications: one
      dissection of the internal carotid artery, two TIAs and two groin haematomas at
      the site of needle access. Neurological examination performed after the procedure
      and during the 30 days of follow-up did not reveal major neurological
      complications. Cerebral protection with a filter during carotid artery stenting
      seemed feasible and safe. 

PMID- 24299600
TI  - Trigeminal perineural spread of head and neck tumors.
AB  - Perineural tumor spread (PNS) of head and neck malignancies is a well-known form
      of metastatic disease in which a lesion can migrate away from the primary site
      along the endoneurium or perineurium. MR imaging is considered the primary method
      for evaluating patients with symptoms related to the trigeminal nerve in most
      clinical settings. Both CT and MR imaging can detect perineural spread, but MRI
      is the modality of choice because of its capability to detect direct signs (nerve
      enlargement and enhancement) and indirect signs (neuropathic muscular atrophy,
      obliteration of fat planes). In addition, MRI is more sensitive because of its
      superior soft-tissue contrast, its multiplanar capability and decreased artifacts
      from dental hardware. Fat suppression images after contrast injection are
      mandatory to better detect nerve enhancement. CT is useful in detecting foraminal
      enlargement or more destructive bone patterns. Nerve function can be perserved
      until later in the course of the disease: patients with perineural spread
      demonstrated at radiologic or pathologic examination may have normal or
      nonspecific nerve function at clinical examination (patients are misdiagnosed
      with Bell's palsy or trigeminal neuralgia). Hence MRI assessment of perineural
      tumor location and extension is important. 

PMID- 24299601
TI  - Ethnobotany and phytopharmacology of Pinus roxburghii Sargent: a plant review.
AB  - Traditional medicine is a blend of information gathered over generations from
      various communities and cultures. Pinus roxburghii Sargent (Pinaceae) commonly
      known as "chir pine" is widely used in traditional and folkloric systems of
      medicine. The all parts of the plant are believed to possess medicinal qualities
      in Ayurvedic and Unani systems of medicine. In these traditional systems of
      medicine, the plant is used to heal many diseases, including afflictions of the
      eyes, ears, throat, blood, and skin. The plant parts are rich in various
      bioactive compounds such as alpha-pinene, abietic acid, quercetin and xanthone.
      Resin acids and flavanoid form a major portion of these bioactive compounds. This
      review presents examples of traditional medicinal uses for P. roxburghii, and
      subsequently explores the current understanding of the chemical, pharmacological,
      and biochemical properties of the extracts and the main active constituents found
      in each tissue of the plant. Clinical trial information is also included where
      available. Careful evaluation of these data may be helpful for scientists and
      researchers to discover and evaluate the specific chemical entities responsible
      for the traditional medicinal uses of P. roxburghii. 

PMID- 24299602
TI  - Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: Due to safety concerns and side effects of many antidepressant
      medications, herbal psychopharmacology research has increased, and herbal
      remedies are becoming increasingly popular as alternatives to prescribed
      medications for the treatment of major depressive disorder (MDD). Of these,
      accumulating trials reveal positive effects of the spice saffron (Crocus sativus
      L.) for the treatment of depression. A comprehensive and statistical review of
      the clinical trials examining the effects of saffron for treatment of MDD is
      warranted. OBJECTIVE: The purpose of this study was to conduct a meta-analysis of
      published randomized controlled trials examining the effects of saffron
      supplementation on symptoms of depression among participants with MDD. SEARCH
      STRATEGY: We conducted electronic and non-electronic searches to identify all
      relevant randomized, double-blind controlled trials. Reference lists of all
      retrieved articles were searched for relevant studies. INCLUSION CRITERIA: The
      criteria for study selection included the following: (1) adults (aged 18 and
      older) with symptoms of depression, (2) randomized controlled trial, (3) effects
      of saffron supplementation on depressive symptoms examined, and (4) study had
      either a placebo control or antidepressant comparison group. DATA EXTRACTION AND
      ANALYSIS: Using random effects modeling procedures, we calculated weighted mean
      effect sizes separately for the saffron supplementation vs placebo control
      groups, and for the saffron supplementation vs antidepressant groups. The
      methodological quality of all studies was assessed using the Jadad score. The
      computer software Comprehensive Meta-analysis 2 was used to analyze the data.
      RESULTS: Based on our pre-specified criteria, five randomized controlled trials
      (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were
      included in our review. A large effect size was found for saffron supplementation
      vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001),
      revealing that saffron supplementation significantly reduced depression symptoms
      compared to the placebo control. A null effect size was evidenced between saffron
      supplementation and the antidepressant groups (M ES = -0.15) indicating that both
      treatments were similarly effective in reducing depression symptoms. The mean
      Jadad score was 5 indicating high quality of trials. CONCLUSION: Findings from
      clinical trials conducted to date indicate that saffron supplementation can
      improve symptoms of depression in adults with MDD. Larger clinical trials,
      conducted by research teams outside of Iran, with long-term follow-ups are needed
      before firm conclusions can be made regarding saffron's efficacy and safety for
      treating depressive symptoms.

PMID- 24299603
TI  - Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and
      viability of perfused lung cells of mice in vitro.
AB  - OBJECTIVE: To examine if the ultra-highly diluted homeopathic remedy Thuja 30C
      can ameliorate benzo(a)pyrene (BaP)-induced DNA damage, stress and viability of
      perfused lung cells of Swiss albino mice in vitro. METHODS: Perfused normal lung
      cells from mice were cultured in 5% Roswell Park Memorial Institute medium and
      exposed to BaP, a potent carcinogen, at the half maximal inhibitory concentration
      dose (2.2 MUmol/L) for 24 h. Thereafter, the intoxicated cells were either
      treated with Thuja 30C (used against tumor or cancer) or its vehicle media,
      succussed alcohol 30C. Relevant parameters of study involving reactive oxygen
      species (ROS) accumulation, total glutathione (GSH) content, and generations of
      heat shock protein (hsp)-90 were measured; the cell viability and other test
      parameters were measured after treatment with either Thuja 30C or its vehicle
      media. Circular dichroism spectroscopy was performed to examine if Thuja 30C
      directly interacted with calf thymus DNA as target. For ascertaining if DNA
      damaged by BaP could be partially repaired and restituted by the remedy, 4',6
      diamidino-2-phenylindole staining was performed. RESULTS: Thuja 30C increased
      cell viability of BaP-intoxicated cells significantly, as compared to drug
      untreated or drug-vehicle control. A minimal dose of Thuja 30C significantly
      inhibited BaP-induced stress level, by down-regulating ROS and hsp-90, and
      increasing GSH content. Thuja 30C itself had no DNA-damaging effect, and no
      direct drug-DNA interaction. However, it showed quite striking ability to repair
      DNA damage caused by BaP. CONCLUSION: Thuja 30C ameliorates BaP-induced toxicity,
      stress and DNA damage in perfused lung cells of mice and it apparently has no
      effect on normal lung cells.

PMID- 24299604
TI  - Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera
      shows anticancer effects on HeLa and PC3 cell lines: signalling pathway and drug
      DNA interaction.
AB  - OBJECTIVE: To test if myricanone (C21H24O5), a cyclic diarylheptanoid, has
      anticancer effects on two different cancer cell lines HeLa and PC3. The present
      study was conducted with a note on the drug-DNA interaction and apoptotic
      signalling pathway. METHODS: Several studies like cytotoxicity, nuclear damage,
      annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)-labelled
      apoptotic assay and cell cycle arrest, immunoblot and reverse transcriptase
      polymerase chain reaction (RT-PCR) were used following standard protocols.
      Circular dichroism (CD) spectroscopy was also done to evaluate whether myricanone
      effectively interacted with DNA to bring about conformational changes that could
      strongly inhibit the cancer cell proliferation. RESULTS: Myricanone showed a
      greater cytotoxic effect on PC3 cells than on HeLa cells. Myricanone promoted
      G0/G1 arrest in HeLa cells and S phase arrest in PC3 cells. Nuclear condensation
      and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell
      death. CD spectroscopic data indicated that myricanone had an interaction with
      calf thymus DNA that changed DNA structural conformation. RT-PCR and immunoblot
      studies revealed that myricanone activated the apoptotic signalling cascades
      through down-regulation of transcription factors like nuclear factor-kappaB (NF
      kappaB) (p65), and signal transducers and activators of transcription 3 (STAT3);
      cell cycle regulators like cyclin D1, and survivin and other signal proteins like
      Bcl-2 and up-regulation of Bax, caspase-9 and caspase-3. CONCLUSION: Myricanone
      induced apoptosis in both types of cancer cells by triggering caspase activation,
      and suppression of cell proliferation by down-regulation of NF-kappaB and STAT3
      signalling cascades, which makes it a suitable candidate for possible use in the
      formulation of therapeutic agent for combating cancer.

PMID- 24299605
TI  - Medical implication in the Bible and its relevance to modern medicine.
AB  - The Holy Bible, as the root of Western civilization, has imposed great influence
      in the fields far beyond religion. In this thesis, the author intended to reveal
      the medical implication in the Holy Bible and its relevance to the modern medical
      science by exploring the biblical medical information and comparing it with the
      current medical theory and practice. The conclusion of the exploration is
      surprising yet inspiring: the Holy Bible, as an ancient religious book, contains
      rich medical information around themes such as sexual relations, dietary
      guidelines, hygiene, etc., which is not at odds, but in harmony with the modern
      medicine. 

PMID- 24299606
TI  - Integrative techniques using acupuncture, Chinese herbal medicine, diet, and
      supplements for polycystic ovary syndrome: a case report.

PMID- 24299607
TI  - Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis:
      study protocol of a multicenter randomized controlled trial.
AB  - BACKGROUND: Rheumatoid arthritis (RA), as a common systemic inflammatory
      autoimmune disease, affects approximately 1 in 100 individuals. Effective
      treatment for RA is not yet available because current research does not have a
      clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a
      patent Chinese herbal medicine, has been used in the treatment of RA in recent
      years. Despite its reported clinical efficacy, there are no large-sample,
      multicenter, randomized trials that support the use of Xinfeng Capsule for RA.
      Therefore, we designed a randomized, double-blind, multicenter, placebo
      controlled trial to assess the efficacy and safety of Xinfeng Capsule in the
      treatment of RA. METHODS AND DESIGN: This is a 12-week, randomized, placebo
      controlled, double-blind, multicenter trial on the treatment of RA. The
      participants will be randomly assigned to the experimental group and the control
      group at a ratio of 1:1. Participants in the experimental group will receive
      Xinfeng Capsule and a pharmaceutical placebo (imitation leflunomide). The control
      group will receive leflunomide and an herbal placebo (imitation Xinfeng Capsule).
      The American College of Rheumatology (ACR) Criteria for RA will be used to
      measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be
      the percentage of study participants who achieve an ACR 20% response rate
      (ACR20), which will be measured every 4 weeks after randomization. Secondary
      outcomes will include the ACR50 and ACR70 responses, the side effects of the
      medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X
      rays of the hands and wrists. The first four of the secondary outcomes will be
      measured every 4 weeks and the others will be measured at baseline and after 12
      weeks of treatment. DISCUSSION: The result of this trial will help to evaluate
      whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL
      REGISTRATION: This trial has been registered in ClinicalTrials.gov. The
      identifier is NCT01774877.

PMID- 24299608
TI  - Chemical chaperones mitigate experimental asthma by attenuating endoplasmic
      reticulum stress.
AB  - Endoplasmic reticulum (ER) stress and consequent unfolded protein response (UPR)
      are important in inflammation but have been poorly explored in asthma. We used a
      mouse model of allergic airway inflammation (AAI) with features of asthma to
      understand the role of ER stress and to explore potential therapeutic effects of
      inhaled chemical chaperones, which are small molecules that can promote protein
      folding and diminish UPR. UPR markers were initially measured on alternate days
      during a 7-day daily allergen challenge model. UPR markers increased within 24
      hours after the first allergen challenge and peaked by the third challenge,
      before AAI was fully established (from the fifth challenge onward). Three
      chemical chaperones-glycerol, trehalose, and trimethylamine-N-oxide (TMAO)-were
      initially administered during allergen challenge (preventive regimen). TMAO, the
      most effective of these chemical chaperones and 4-phenylbutyric acid, a chemical
      chaperone currently in clinical trials, were further tested for potential
      therapeutic activities after AAI was established (therapeutic regimen). Chemical
      chaperones showed a dose-dependent reduction in UPR markers, airway inflammation,
      and remodeling in both regimens. Our results indicate an early and important role
      of the ER stress pathway in asthma pathogenesis and show therapeutic potential
      for chemical chaperones.

PMID- 24299609
TI  - Ultrasensitive gas-phase chemical sensing based on functionalized photonic
      crystal nanobeam cavities.
AB  - Photonic crystal nanobeam cavities with high-quality factors are very sensitive
      to the changes of the dielectric properties of their surroundings. Utilizing this
      high sensitivity and by applying chemical functionalization, an ultrasensitive
      chemical sensor for gases based on a nanobeam cavity was demonstrated. A limit of
      detection of 1.5 parts-per-billion (ppb) in ambient conditions, determined from
      the noise level of the system, was achieved for nerve agent simulant methyl
      salicylate. The nanobeam cavity's nonlinear thermo-optical bistability is also
      utilized to realize a threshold detector for cumulative chemical exposure. 

PMID- 24299610
TI  - Nursing diagnosis of grieving: content validity in perinatal loss situations.
AB  - PURPOSE: To validate the content of the NANDA-I nursing diagnosis of grieving in
      situations of perinatal loss. METHODS: Using the Fehring's model, 208 Spanish
      experts were asked to assess the adequacy of the defining characteristics and
      other manifestations identified in the literature for cases of perinatal loss.
      FINDINGS: The content validity index was 0.867. Twelve of the 18 defining
      characteristics were validated, seven as major and five as minor. From the
      manifestations proposed, "empty inside" was considered as major. CONCLUSION: The
      nursing diagnosis of grieving fits in content to the cases of perinatal loss
      according to experts. IMPLICATIONS FOR NURSING PRACTICE: The results have
      provided evidence to support the use of the diagnosis in care plans for said
      clinical situation.

PMID- 24299611
TI  - Brain regional homogeneity changes following transjugular intrahepatic
      portosystemic shunt in cirrhotic patients support cerebral adaptability theory--a
      resting-state functional MRI study.
AB  - PURPOSE: The exact neuro-pathophysiological effect of transjugular intrahepatic
      portosystemic shunt (TIPS) on brain function remains unclear. The purpose of this
      study was to investigate the longitudinal brain activity changes in cirrhotic
      patients with TIPS insertion using resting-state functional MRI (fMRI) with
      regional homogeneity (ReHo) method. METHODS: Fifteen cirrhotic patients without
      overt hepatic encephalopathy (OHE) planned for TIPS procedure and 15 age- and
      gender-matched healthy controls were included in this study. Eleven of the 15
      patients underwent repeated fMRI examinations at median 7-day following TIPS, 8
      patients in median 3-month, and 7 patients in median 1-year follow-up duration,
      respectively. Regional homogeneity was calculated by the Kendall's coefficient of
      concordance (KCC) and compared between patients before TIPS and healthy controls
      with two-sample t test as well as pre-and post-TIPS patients with paired t test.
      Correlations between the pre- and post-TIPS changes of ReHo and the changes of
      venous blood ammonia level and number connection test type A (NCT-A)/digit symbol
      test (DST) scores were calculated by crossing subjects. RESULTS: Compared with
      healthy controls, 15 cirrhotic patients before TIPS procedure showed decreased
      ReHo in the bilateral frontal, parietal, temporal and occipital lobes and
      increased ReHo in the bilateral caudate. Compared with the pre-TIPS patients, 11
      post-TIPS patients in the median 7-day follow-up examinations demonstrated
      decreased ReHo in the medial frontal gyrus (MFG), superior parietal gyrus (SPG),
      middle/superior temporal gyrus (M/STG), anterior cingulate cortex (ACC), caudate,
      and increased ReHo in the insula. Eight post-TIPS patients in the median 3-month
      follow-up examinations showed widespread decreased ReHo in the bilateral frontal
      and parietal lobes, ACC, caudate, and increased ReHo in the insula and
      precuneus/cuneus. In the median 1-year follow-up studies, seven post-TIPS
      patients displayed decreased ReHo in the bilateral frontal and parietal lobes,
      ACC, supplementary motor area (SMA), posterior cingulate cortex (PCC), and
      increased ReHo in the caudate and insula (P<0.05, Alphasim corrected). The
      changes of ReHo values in bilateral IPL, MFG, caudate and SMA were correlated
      with changes of DST scores during the median 3-month follow-up (all P<0.05).
      CONCLUSION: The TIPS implantation had a persistent effect on brain function in
      cirrhotic patients including both predominant impairment and compensation
      mechanisms, with the most significant alterations in the median 3-month period
      after TIPS. The ReHo analysis may be potentially valuable for uncovering the
      mechanism of TIPS' effects on brain function.

PMID- 24299612
TI  - Morphological and physiological properties of enhanced green fluorescent protein
      (EGFP)-expressing wide-field amacrine cells in the ChAT-EGFP mouse line.
AB  - Mammalian retinas comprise a variety of interneurons, among which amacrine cells
      represent the largest group, with more than 30 different cell types each
      exhibiting a rather distinctive morphology and carrying out a unique function in
      retinal processing. However, many amacrine types have not been studied
      systematically because, in particular, amacrine cells with large dendritic
      fields, i.e. wide-field amacrine cells, have a low abundance and are therefore
      difficult to target. Here, we used a transgenic mouse line expressing the coding
      sequence of enhanced green fluorescent protein under the promoter for choline
      acetyltransferase (ChAT-EGFP mouse) and characterized a single wide-field
      amacrine cell population monostratifying in layer 2/3 of the inner plexiform
      layer (WA-S2/3 cell). Somata of WA-S2/3 cells are located either in the inner
      nuclear layer or are displaced to the ganglion cell layer and exhibit a low cell
      density. Using immunohistochemistry, we show that WA-S2/3 cells are presumably
      GABAergic but may also release acetylcholine as their somata are weakly positive
      for ChAT. Two-photon-guided patch-clamp recordings from intact retinas revealed
      WA-S2/3 cells to be ON-OFF cells with a homogenous receptive field even larger
      than the dendritic field. The large spatial extent of the receptive field is most
      likely due to the extensive homologous and heterologous coupling among WA-S2/3
      cells and to other amacrine cells, respectively, as indicated by tracer
      injections. In summary, we have characterized a novel type of GABAergic ON-OFF
      wide-field amacrine cell which is ideally suited to providing long-range
      inhibition to ganglion cells due to its strong coupling. 

PMID- 24299613
TI  - Incidence of type II diabetes in a cohort with substantial exposure to
      perfluorooctanoic acid.
AB  - BACKGROUND: Research suggests an increased type II diabetes mortality risk among
      workers occupationally exposed to PFOA. However, a cross-sectional study of
      highly exposed Mid-Ohio Valley community residents did not demonstrate an
      association between PFOA and type II diabetes. OBJECTIVES: We examined the
      relationship between exposure to PFOA over time and incidence of type II diabetes
      in a cohort of community residents and workers exposed to high levels of PFOA via
      contaminated drinking water. METHODS: Community residents and workers were
      interviewed in 2008-2011 to obtain medical history and other demographic
      information. Cumulative serum PFOA exposure estimates were calculated based on
      residence and occupation locations, and a history of plant emissions. We
      estimated the risk of developing type II diabetes using Cox proportional hazard
      models, controlling for demographic characteristics and family history. RESULTS:
      Out of 32,254 survey respondents, there were 4434 cases of self-reported type II
      diabetes, of which 4129 were validated through medical record review. In analyses
      based on validated type II diabetes, there was no trend of increased risk with
      increased cumulative PFOA serum levels (HRs compared to lowest exposure decile:
      0.91 (95% CI: 0.76-1.08), 1.18 (95% CI: 0.99-1.40), 0.96 (95% CI: 0.81-1.15),
      1.04 (95% CI: 0.87-1.24), 1.11 (95% CI: 0.93-1.32), 1.06 (95% CI: 0.89-1.26),
      1.00 (95% CI: 0.85-1.19), 1.03 (95% CI: 0.86-1.23), 1.01 (95% CI: 0.84-1.20)).
      There was no association between fasting glucose level and cumulative serum
      levels of PFOA, after excluding diabetics. CONCLUSIONS: We do not find an
      association between PFOA exposure and incidence of type II diabetes.

PMID- 24299614
TI  - The Effects of Exenatide Microsphere on Serum BGP and ALP Levels in ZDF Rats
      after Implantation.
AB  - PURPOSE: The aim of this project is to investigate the impact of diabetes
      mellitus and different glycemic control times on early osseointegration of dental
      implants by expression and significance of serum bone Gla protein (BGP) and
      alkaline phosphatase (ALP) levels in Zucker diabetic fatty (ZDF) rats after
      implantation. MATERIALS AND METHODS: The animals were divided into three groups,
      each group with 11 rats and each rat with two dental implants (33 rats and 66
      implants in total): group A, diabetic rats with dental implants (controls); group
      B, diabetic rats treated with insulin and implants placed simultaneously; and
      group C, diabetic rats treated with insulin until serum glucose at a constant
      level and then implants be placed. Levels of BGP and ALP in the serum were
      measured by enzyme-linked immunosorbent assay in each group. The software program
      SPSS (version 17.0 for Windows) was used to analyze all data; p < .05 was set as
      the level of statistical significance. RESULTS: At the 7th day, serum levels of
      BGP in group B and C were lower than that in group A (p > 0.05). At the 14th day,
      serum levels of BGP in group C were significantly higher (p < 0.05). After 30
      days, compared with group A, the serum levels of BGP in group B and C seems to be
      lower. Compared with group A, the serum levels of ALP in group B and C were
      significantly higher, whereas the serum levels of ALP in group C seems to be
      higher than B (p < 0.05). CONCLUSIONS: The present results suggest that injection
      of delayed release microsphere of exenatide on ZDF rats can release exenatide at
      a steady rate and the blood glucose can be controlled at a constant level.
      Implant survival rates could be enhanced in DM subjects when blood plasma glucose
      level is under control; the serum levels of BGP in this study seems to have no
      relationship with local osseointegration, whereas the serum levels of ALP might
      offer insights into the activity of osseointegration around the implant surface.

PMID- 24299615
TI  - Concha bullosa mucocele with orbital invasion and secondary frontal sinusitis: a
      case report.
AB  - BACKGROUND: Although concha bullosa (CB) is the most common variants of the
      middle turbinate, mucocele of CB is uncommon. Furthermore, CB mucocele with
      orbital invasion and secondary frontal sinusitis has not been reported
      previously. CASE PRESENTATION: A 42-year-old Korean male presented with gradually
      progressive proptosis of right eye and right-sided frontal headache. He had
      previously undergone endoscopic sinus surgery (ESS) 15 and 9 years ago. The
      endoscopic examination showed an expansive, large middle turbinate with normal
      mucosa filled the majority of right nasal cavity and displaced the septum to the
      left. A computed tomography and magnetic resonance imaging showed a well
      demarcated cystic huge mass at right nasal cavity extending to ethmoid sinus and
      orbit. The mass caused a bony defect on the lamina papyracea and displaced medial
      rectus muscle and orbit laterally. Moreover, the right frontal and ethmoid sinus
      was totally opacified. This article reports orbital invasion and frontal
      sinusitis complicating a CB mucocele, which was successfully treated by
      endoscopic resection of the lateral wall of CB and frontal sinusotomy.
      CONCLUSIONS: This case illustrates that CB mucocele could develop to such a
      massive extent that it leads to orbital complication and secondary frontal
      sinusitis. Therefore, we consider this entity in the differential diagnosis of
      orbital complications and secondary sinusitis caused by intranasal mass.

PMID- 24299617
TI  - Glycated haemoglobin variations in paediatric type 1 diabetes: the impact of
      season, gender and age.
AB  - AIM: To study whether monthly variations in type 1 diabetes incidence are related
      to monthly glycated haemoglobin (HbA1c) levels at diagnosis and if high HbA1c at
      diagnosis is related to certain clinical variables at diagnosis and during the
      clinical course of the disease. METHODS: Data from 4430 boys and 3590 girls
      registered in the Swedish paediatric diabetes quality registry, Swedish
      paediatric diabetes quality registry, from 2000 to 2010 were analysed. RESULTS:
      Month of onset varied (p < 0.001), with 53% diagnosed during September to
      February, and mean HbA1c at diagnosis was highest in May (10.9%, 96 mmol/mol) and
      lowest in (October 9.4%, 88 mmol/mol) (p < 0.001). Girls showed higher HbA1c at
      onset than boys (p < 0.001). More than half (53%) with an annual mean HbA1c of
      >9.3% (78 mmol/mol) and 4% of those with an annual mean of <7.4% (57 mmol/mol) in
      2007 had >9.3% (78 mmol/mol) in 2010. CONCLUSION: Patients with high HbA1c levels
      during a certain period have the same high levels several years later. This
      group, perhaps including those with high HbA1c level at diagnosis, may need more
      intensive care, including extra support from the diabetes teams and other forms
      of medical treatment.

PMID- 24299616
TI  - Inhibitory effect of a callophycin A derivative on iNOS expression via inhibition
      of Akt in lipopolysaccharide-stimulated RAW 264.7 cells.
AB  - In previous studies, (R)-2-isobutyl 3-methyl 3,4-dihydro-1H-pyrido[3,4-b]indole
      2,3(9H)-dicarboxylate (1), a callophycin A derivative, was found to strongly
      inhibit nitrite production in lipopolysaccharide (LPS)-stimulated RAW 264.7
      cells, while (R)- or (S)-callophycin A showed only weak inhibition. We currently
      report additional studies to define the mechanisms underlying the inhibitory
      action of 1. Expression of inducible nitric oxide synthase (iNOS) was reduced at
      both protein and mRNA levels. Major upstream signaling molecules and
      transcription factors regulating iNOS expression were examined, but it was found
      that 1 did not affect the phosphorylated and total protein levels of p38 mitogen
      activated protein kinase (p38 MAPK), Jun N-terminal kinase (JNK), extracellular
      signal-regulated kinase 1/2 (ERK1/2), and signal transducer and activator of
      transcription 1 (STAT1), nor did it mediate the degradation of the inhibitor of
      nuclear factor-kappaB alpha-isoform (IkappaBalpha). However, starting at early
      time points, 1 consistently inhibited the phosphorylation of protein kinase B/Akt
      at serine 473. In addition, 1 suppressed the protein expression of octamer
      binding transcription factor-2 (Oct-2) and the expression of microRNA 155 (miR
      155). In sum, compound 1 inhibits LPS-induced nitrite production by a unique and
      complex mechanism. Reduction of iNOS expression is accompanied by inhibition of
      Akt activation, Oct-2 protein expression, and miR-155 expression. 

PMID- 24299618
TI  - Reducing the risk in neonatal anesthesia.
AB  - Neonatal anesthesia is fraught with potential risk for the patient and stress for
      the anesthesiologist. Where possible, recognition of these risks, avoidance of,
      and being able to manage them appropriately, must impact positively on
      perioperative outcomes in this vulnerable group of patients. Good communication
      with the parents, as well as with other healthcare providers, is crucial to safe
      and successful anesthetic care. 

PMID- 24299619
TI  - Tailoring the surface properties of tobacco mosaic virions by the integration of
      bacterially expressed mutant coat protein.
AB  - Due to its small dimensions and high stability, tobacco mosaic virus (TMV) is
      used as nano-scaffold frequently. Its surface can be engineered to meet specific
      needs for technical, medical or materials applications. However, not all
      technically desirable TMV coat protein (CP) mutants can be propagated in plants
      successfully, if they change the efficiency of virion assembly. In order to
      circumvent this problem, a novel wild type (wt) CP-assisted and RNA-directed
      assembly procedure was designed for a recalcitrant CP mutant: Although pure
      hexahistidine-tagged CP cannot form particles on its own with TMV RNA in vitro,
      it was integrated into full-length particles if blended with wt CP in different
      proportions. The resulting rods formed dense monolayers with short range
      alignment on silicon substrates, substantially different from the largely wavy
      patterns obtained with wt TMV. Since they also mediated efficient ZnO deposition
      under mild conditions, the approach has yielded a new class of biotemplates which
      are amenable to the formation of nanostructured hybrid materials with adjustable
      texture for various applications. 

PMID- 24299620
TI  - A decade in dental care utilization among adults and children (2001-2010).
AB  - OBJECTIVE: To decompose the change in pediatric and adult dental care utilization
      over the last decade. DATA: 2001 through 2010 Medical Expenditure Panel Survey.
      STUDY DESIGN: The Blinder-Oaxaca decomposition was used to explain the change in
      dental care utilization among adults and children. Changes in dental care
      utilization were attributed to changes in explained covariates and changes due to
      movements in estimated coefficients. Controlling for demographics, overall health
      status, and dental benefits variables, we estimated year-specific logistic
      regression models. Outputs from these models were used to compute the Blinder
      Oaxaca decomposition. PRINCIPAL FINDINGS: Dental care utilization decreased from
      40.5 percent in 2001 to 37.0 percent in 2010 for adults and increased from 43.2
      percent in 2001 to 46.3 percent in 2010 for children (p<.05). Among adults,
      changes in insurance status, race, and income contributed to a decline in adult
      dental care utilization (-0.018, p<.01). Among children, changes in controlled
      factors did not substantially change dental care utilization, which instead may
      be explained by changes in policy, oral health status, or preferences.
      CONCLUSIONS: Dental care utilization for adults has declined, especially among
      the poor and uninsured. Without further policy intervention, disadvantaged adults
      face increasing barriers to dental care.

PMID- 24299623
TI  - [A man with a swollen shoulder].
AB  - A 25-year-old patient presented to the Emergency Department with a swollen left
      shoulder after an epileptic seizure. Radiography showed a fracture of the humeral
      head. A CT-scan of the shoulder confirmed the diagnosis of an avulsion fracture
      of the lesser tuberosity. This is a rare condition and deserves specific
      attention and surgical treatment to prevent impaired function of the shoulder due
      to muscle weakness and impingement of the avulsion fragment. 

PMID- 24299622
TI  - Xenon and other volatile anesthetics change domain structure in model lipid raft
      membranes.
AB  - Inhalation anesthetics have been in clinical use for over 160 years, but the
      molecular mechanisms of action continue to be investigated. Direct interactions
      with ion channels received much attention after it was found that anesthetics do
      not change the structure of homogeneous model membranes. However, it was recently
      found that halothane, a prototypical anesthetic, changes domain structure of a
      binary lipid membrane. The noble gas xenon is an excellent anesthetic and
      provides a pivotal test of the generality of this finding, extended to ternary
      lipid raft mixtures. We report that xenon and conventional anesthetics change the
      domain equilibrium in two canonical ternary lipid raft mixtures. These findings
      demonstrate a membrane-mediated mechanism whereby inhalation anesthetics can
      affect the lipid environment of transmembrane proteins. 

PMID- 24299621
TI  - The intra- and inter-rater reliability of five clinical muscle performance tests
      in patients with and without neck pain.
AB  - BACKGROUND: This study investigates the reliability of muscle performance tests
      using cost- and time-effective methods similar to those used in clinical
      practice. When conducting reliability studies, great effort goes into
      standardising test procedures to facilitate a stable outcome. Therefore, several
      test trials are often performed. However, when muscle performance tests are
      applied in the clinical setting, clinicians often only conduct a muscle
      performance test once as repeated testing may produce fatigue and pain, thus
      variation in test results. We aimed to investigate whether cervical muscle
      performance tests, which have shown promising psychometric properties, would
      remain reliable when examined under conditions similar to those of daily clinical
      practice. METHODS: The intra-rater (between-day) and inter-rater (within-day)
      reliability was assessed for five cervical muscle performance tests in patients
      with (n = 33) and without neck pain (n = 30). The five tests were joint position
      error, the cranio-cervical flexion test, the neck flexor muscle endurance test
      performed in supine and in a 45 degrees -upright position and a new neck extensor
      test. RESULTS: Intra-rater reliability ranged from moderate to almost perfect
      agreement for joint position error (ICC >= 0.48-0.82), the cranio-cervical
      flexion test (ICC >= 0.69), the neck flexor muscle endurance test performed in
      supine (ICC >= 0.68) and in a 45 degrees -upright position (ICC >= 0.41) with the
      exception of a new test (neck extensor test), which ranged from slight to
      moderate agreement (ICC = 0.14-0.41). Likewise, inter-rater reliability ranged
      from moderate to almost perfect agreement for joint position error (ICC >= 0.51
      0.75), the cranio-cervical flexion test (ICC >= 0.85), the neck flexor muscle
      endurance test performed in supine (ICC >= 0.70) and in a 45 degrees -upright
      position (ICC >= 0.56). However, only slight to fair agreement was found for the
      neck extensor test (ICC = 0.19-0.25). CONCLUSIONS: Intra- and inter-rater
      reliability ranged from moderate to almost perfect agreement with the exception
      of a new test (neck extensor test), which ranged from slight to moderate
      agreement. The significant variability observed suggests that tests like the neck
      extensor test and the neck flexor muscle endurance test performed in a 45 degrees
      -upright position are too unstable to be used when evaluating neck muscle
      performance.

PMID- 24299624
TI  - [Non-transferrin-bound iron: a promising biomarker in iron overload disorders].
AB  - Iron overload disorders are common and, if left untreated, severe systemic
      diseases that can have both genetic and acquired causes. Hereditary
      haemochromatosis, beta-thalassaemia, myelodysplastic syndromes and sickle cell
      disease are among the most important examples. Iron that is not bound to
      transferrin, haem or ferritin (non-transferrin-bound iron, NTBI) seems to play a
      key role in the pathophysiology of these disorders. NTBI is a heterogeneous group
      of potentially toxic iron complexes in plasma which are generated almost
      exclusively under pathological conditions. Cellular uptake of NTBI contributes to
      its toxicity and is mediated by several organ-specific transporters and
      receptors. NTBI-induced toxicity is the result of oxidative damage to various
      macromolecules by reactive oxygen species (ROS). In the near future, we
      hypothesize that NTBI will have important implications for both diagnosis and
      treatment of iron overload disorders. However, before NTBI can be applied to
      patient care, the currently available assays need further clinical and analytical
      validation.

PMID- 24299625
TI  - [Skier's thumb].
AB  - Skier's thumb is a partial or complete rupture of the ulnar collateral ligament
      of the metacarpophalangeal joint of the thumb. It is an injury that rather
      frequently occurs in certain sports. When diagnosed incorrectly, delay in
      treatment can ultimately lead to chronic instability and pain. Correct knowledge
      of the anatomy and method of physical examination is essential when assessing a
      patient suspected of having skier's thumb. This article describes three different
      types and treatment of skier's thumb, and further describes the relevant anatomy,
      correct physical examination, available additional imaging and various treatments
      possible. 

PMID- 24299626
TI  - [Off-label use of biologics for rare immunological disorders].
AB  - Patients with severe therapy-refractory immune-mediated inflammatory diseases
      (IMIDs) are increasingly treated with biologics. Since official practice
      guidelines for these rare diseases are lacking, these drugs are often prescribed
      off-label. However, treating physicians encounter difficulties and risks when
      prescribing drugs off-label. Access to these biologics for off-label indications
      is currently not well organized, which may result in suboptimal care. This also
      blocks innovation in patient care. In this article we introduce the recently
      initiated RUBRIC (Rational Use of Biologics in Refractory Immune-mediated
      inflammatory diseases Consortium) register. This national register documents the
      efficacy and safety of off-label biologic treatment in combination with the
      development of treatment protocols and practice guidelines. We believe that the
      results from this register will ultimately lead to a more evidence-based use of
      biologics in patients with rare IMIDs, which may also result in better access to
      these drugs. Ultimately, both the individual patient and the group as a whole
      will benefit. 

PMID- 24299627
TI  - [Neonaticide: frequently suspected, seldom proven].
AB  - OBJECTIVE: To present an overview of pathological findings on neonaticide in the
      Netherlands. DESIGN: Retrospective descriptive study. METHOD: We analyzed all
      autopsy reports on neonates from the Netherlands Forensic Institute for the
      period 1994-2011. We collected data on gestational age, how the body had been
      discovered and autopsy results. RESULTS: We included details of 78 victims; 61
      (78%) had been born at full term and 17 (22%) prematurely. Half of the victims
      were girls, 40% were boys and in 10% the state of the body meant that it was not
      possible to determine the sex. Minimal, moderate and severe putrefaction was
      observed in 29 bodies (37%), 15 bodies (19%) and 34 bodies (44%), respectively.
      In the cases with moderate or severe decomposition it was not possible to
      determine with certainty whether the child had been born alive and, if
      applicable, the cause of death. Of the remaining 29 cases with minimal
      decomposition, 1 had been stillborn; a possible cause of death could be
      determined in 12 cases. CONCLUSION: In the Netherlands 4 to 5 forensic autopsies
      are performed annually in cases of suspected neonaticide. In most cases
      decomposition is already too advanced to be able to determine whether there was
      any sign of life at birth and to establish the cause of death, if applicable.

PMID- 24299628
TI  - [CT scans in children and adolescents: only when appropriate and when optimized].
AB  - Radiation exposure due to medical imaging has more than doubled in the
      Netherlands since the early 1990 s. There is increasing evidence that this is not
      without risk, especially in children and adolescents. A recent study in over
      680,000 Australians < 19 years old at the time of imaging provides further
      evidence that CT scanning may induce excess cancer. In light of these findings it
      is of paramount importance that physicians dealing with this patient population
      only request CT studies if imaging is clearly indicated. New technological
      developments such as iterative reconstruction will ameliorate the risk for low
      radiation-dose malignancies, but continued vigilance is necessary.

PMID- 24299629
TI  - [Unexpected abdominal trauma from a fireworks explosion].
AB  - BACKGROUND: Fireworks injuries are common and often affect children. Such
      injuries should be considered high energy trauma in the emergency room and taken
      care of according to the principles of the Advanced Trauma Life Support (ATLS).
      CASE DESCRIPTION: A 7-year-old boy was a victim of an explosion when he set off
      illegal fireworks. During evaluation in the emergency department he presented
      with a superficial laceration on the belly and extensive hand injury. Upon
      examination he had small-intestinal perforation that required immediate
      resection. The patient recovered well, but suffered permanent damage to the hand.
      CONCLUSION: Potentially life threatening injuries may accompany hand injuries
      after modern illegal fireworks. Hand injuries are serious. Despite prolonged
      treatment, they often result in permanent disability. The structured approach to
      trauma according to ATLS was important in detecting an accompanying abdominal
      trauma in this case.

PMID- 24299630
TI  - [A woman with acute abdominal pain in the night].
AB  - A 43-year-old woman came to the Emergency Room with acute abdominal pain during
      the night. CT examination of the abdomen showed ventral herniation of the stomach
      and parts of the small intestine and colon in the right hemithorax. We made the
      diagnosis 'symptomatic Morgagni hernia', a rare congenital defect that is usually
      diagnosed soon after birth. 

PMID- 24299633
TI  - Welcome SILAN!

PMID- 24299631
TI  - ['Postoperative pain treatment' practice guideline revised].
AB  - On the initiative of the Dutch Association of Anaesthesiologists, a
      multidisciplinary workgroup has revised the 2003 practice guideline on
      'Postoperative pain treatment' for adults and children. The main reason for
      revision was the availability of new drugs and new methods of administration. The
      most important deviations from the previous edition are the following. The
      organisation of care has been amended according to the current themes of the
      Safety Management System in the Netherlands, and a prediction model for
      postoperative pain was added. The drugs oxycodone, S-ketamine, pregabalin,
      gabapentin and metamizole were added, as well as new methods of administration
      and techniques for preventing postoperative pain. This revised guideline is more
      conservative than the previous one in the choice of epidural analgesia. In
      patients with relative contraindications for epidural analgesia, peripheral and
      locoregional blocks or multimodal pain treatment are advised. In the case of
      postoperative nausea and vomiting, administration of dexamethasone, droperidol
      and 5-HT3-antagonists is recommended, preferably in combination. Non-medicinal
      treatment options are not recommended.

PMID- 24299634
TI  - Influence of user-defined parameters on diffusion tensor tractography of the
      corticospinal tract.
AB  - This study discusses the influence of user-defined parameters on fiber tracking
      results obtained from a standard deterministic streamline tractography algorithm.
      Diffusion tensor imaging with fiber tractography was performed in five healthy
      volunteers. A region of interest was highlighted in the ventral part of the pons
      at the level of the middle cerebellar peduncle. The parameters studied were angle
      threshold, fractional anisotropy threshold, step length and number of seed
      samples per voxel. Changes in fiber tracts were described for increasing values
      per parameter. Increasing the angle threshold resulted in more and longer fibers.
      A higher fractional anisotropy threshold resulted in decreased length and fiber
      tracts that were not representative. Increasing the step length decreased the
      fiber continuity and altered its position. A higher number of seed samples per
      voxel resulted in a higher fiber tract density. When interpreting diffusion
      tensor images, the reader should understand the influence of user-defined
      settings on the results, and should be aware of the inter-dependency of fiber
      tracking parameters. 

PMID- 24299635
TI  - Characterization of focal brain lesions by gradient-echo arterial spin-tagging
      perfusion imaging.
AB  - A simple gradient-echo arterial spin tagging (GREAST) technique allows for quick
      assessment of regional tissue perfusion without the need for exogenous contrast
      agent. The purpose of this prospective study was to validate GREAST imaging in
      characterizing the regional perfusion status of focal brain lesions by comparing
      with relative cerebral blood volume (rCBV) maps obtained by using echo-planar
      imaging (EPI)-based dynamic susceptibility contrast MR imaging. Thirty-two
      patients whose nonenhanced brain MR images showed 34 focal brain lesions during
      routine examination were selected to immediately undergo GREAST and dynamic
      susceptibility contrast MR imaging to evaluate regional perfusion of the lesions.
      The Pearson correlation coefficient was used to test the relative quantification
      of local perfusion with the two imaging methods. Qualitative perfusion
      measurements agreed in 23 (79%) of 29 lesions for which GREAST and dynamic
      susceptibility contrast MR imaging were successful. On rCBV maps, six focal
      lesions with local hemorrhage were underestimated. In three patients with metal
      surgical implants, lesions could not be measured because of susceptibility
      artifacts and distortion on EPIs. After these lesions were excluded, the Pearson
      correlation coefficient between relative quantitative perfusion measurements on
      GREAST images versus rCBV maps was about 0.90 (p value = 0.000). The success rate
      of GREAST imaging was 94% (30 of 32 patients), higher than that of dynamic
      susceptibility contrast MR imaging (72%, or 23 of 32 patients). GREAST imaging
      was comparable to rCBV mapping for the relative quantification of regional
      perfusion of focal brain lesions. This technique may be useful in routine MR
      examination for characterizing the regional perfusion of brain focal lesions. 

PMID- 24299636
TI  - Functional magnetic resonance imaging for cranial neuronavigation: methods for
      automated and standardized data processing and management. A technical note.
AB  - Preoperative fMRI is one of the best established clinical fMRI applications. Due
      to the difficulties in recording and coregistration of functional image data, we
      present methods to standardize and automate these procedures. We used a self-made
      interactive software package (AFI - Automated Functional Imaging) to automate the
      time consuming and complex analysis of fMRI data. AFI controls the BrainVoyager
      program, a postprocessing software package, and furthermore facilitates data
      management, anonymization of patient data, storage, documentation, data export to
      neuronavigation systems and the opportunity of spatial transformation of image
      data for use in group studies. By the end of 2006 we have used this method on 123
      patients with brain tumors and 47 patients with trigeminal neuralgia. The
      fundamental basis of multimodal neuronavigation is precise coregistration. EPI
      images contain spatial distortions of 5-15 mm. We were able to reduce the
      misregistration of EPI and FLASH images in a selectable region of interest to 1-2
      mm. Furthermore AFI reduces the average evaluation time for a standard clinical
      fMRI study (four functional measurements, one anatomical data set) by approx. 50%
      from 140 minutes to about 70 minutes in comparison to manual evaluation by an
      expert. More importantly, the personal attendance time required for the
      evaluation decreases by 84% to 23 minutes as the remainder of the program runs
      automatically. In comparison to currently available online postprocessing
      software tools which are more limited in use, BrainVoyager can be used for
      coregistration, data export to neuronavigation systems and spatial
      transformation. 

PMID- 24299637
TI  - Preoperative integrated imaging in paediatric cochlear implantation.
AB  - Sensorineural hearing loss affects one to two children out of 1000 born
      apparently healthy and 9% approximately of those born with the risk of different
      pathologies. The origin of premature deafness is unknown in 25% of children
      whereas it is genetic in some cases. Prevention and early diagnosis, possibly
      within six to eight months, aim to avoid deafness becoming a cause of disability.
      The aim of the present study was to establish the optimal preoperative assessment
      with a diagnostic imaging protocol involving the integrated use of CT and MRI in
      the selection of the candidates for cochlear implantation. Twenty children were
      assessed, divided into three different groups: A) those who had CT only; B) those
      who had only MR; C) those who had both CT and MRI. The purpose was to estimate
      diagnostic accuracy in preoperative planning and the role of imaging in the
      diagnostic protocol for children's deafness. The petrous pyramid was studied with
      a CT Picker PQ 6000 system to high resolution in the axial and coronal planes,
      and with an MR Intera Philips 0.5 T device by means of acquisition of sequences B
      TFE T2 3D and MIP reconstructions on radial coronal plans. This study was
      completed successfully for morphological brain MRI examination to complete the
      diagnosis. The following abnormalities were found in six patients (30%): one case
      of incomplete partition (Mondini malformation); two cases of vestibular aqueduct
      enlargement; two cases with anomalous jugular bulb positioning; one case with
      cochlear ossification. In the remaining 70%: eight patients had no anatomical
      anomalies; CT and MRI imaging were normal in six patients with minor
      abnormalities disclosed at surgery (one case of the stapedial artery emerging
      from the promontory); three anatomical variants of the round window, and two
      abnormal course of the facial nerve). We emphasize the importance of integrated
      CT and MRI imaging in the study of children with sensorineural hearing loss. The
      combination of CT and MRI has been shown to be superior to either modality used
      alone in view of "risk-free" cochear implantation. High resolution computed
      tomography and magnetic resonance images obtained by B-TFE T2-weighted 3D
      sequences help the surgeon in planning the operation and predict operative
      difficulty and potential complications in paediatric cochlear implant candidates.

PMID- 24299638
TI  - MRI findings of globe and optic nerves in tilted disk syndrome.
AB  - We assessed the anatomical variations of the globe and optic nerve in tilted disk
      (TD) syndrome using magnetic resonance imaging (MRI) findings and compared them
      with a control group. Eleven patients diagnosed with TD syndrome during eye
      examination were referred for MRI of the sella and chiasm to exclude intracranial
      mass lesions. The shape of the globe, the chiasmal angle, the insertion angles of
      the optic nerve in axial and parasagittal planes determined by lines parallel to
      the optic nerve and tangent to the globe in TD syndrome were compared with a
      control group consisting of 53 cases. Gender ratios were 7/4 (F/M) for the TD
      group and 35/18 for the control group (p>0.05). The insertion angle of the optic
      disk to the globe was wider in the temporal quadrant (p<0.05) and narrower in the
      nasal quadrant (p<0.05) in TD syndrome than in the control group. There was no
      significant difference in the superior and inferior insertion angles between the
      groups. The anterior-posterior (AP) diameter of the globe was significantly
      longer in patients with TD (p<0.05). There was no significant difference between
      the optic chiasm angles. The relationships of the optic disk and the globe were
      significantly different in patients with TD syndrome in comparison to the control
      group. TD syndrome is related to the malalignment of optic nerve and globe in the
      horizontal plane. 

PMID- 24299639
TI  - Bilateral staphylomas presenting as bitemporal hemianopia.
AB  - Bitemporal hemianopia is usually secondary to pituitary and suprasellar masses.
      We present a case of bitemporal hemianopia secondary to bilateral staphylomas of
      the ocular globe. Staphylomas are degenerative outpouchings of the eyeball also
      known as scleral ectasia, secondary to congenital weakness of scleral tissue.
      Staphylomas can cause complications such as choroidal neovascularizations and
      hemorrhage. Early diagnosis and counselling are the mainstays of management.
      Bilateral staphylomas should be considered in the differential diagnosis of
      bitemporal hemianopia especially when imaging rules out sellar and suprasellar
      masses. 

PMID- 24299640
TI  - Partial Rhombencephalosynapsis of the Superior Cerebellum Associated with GM1
      Gangliosidosis.

PMID- 24299641
TI  - Persistent primitive trigeminal artery in monochorial twins. A case report.
AB  - The trigeminal artery is one of the arterial structures that constitute
      anastomosis between the carotid and the posterior circulation during fetal life
      and usually regress. However these arterial structures may persist in adult life
      and the trigeminal artery is the one that most frequently show such behaviour. We
      describe the case of two monochorial female twins with a persistent primitive
      trigeminal artery revealed by magnetic resonance angiography. 

PMID- 24299642
TI  - Multiple intracranial hemorrhages after evacuation of bilateral subdural
      effusions.
AB  - Postoperative intracerebral hemorrhages occurring after evacuation of subdural
      fluid collections have been infrequently reported and remain a devastating
      complication. The pathophysiological mechanism is still unclear. Disturbed
      autoregulation and restoration of normal cerebral flow seems to play an important
      role in this type of event because of rapid decompression. Herein, we present a
      case of multiple intracerebral hemorrhages in the putamen and cerebellar
      hemisphere following evacuation of bilateral subdural effusions, and review the
      relevant literature. 

PMID- 24299643
TI  - 'Eiffel-by-Night': A New MR Sign Demonstrating Reactivation in Idiopathic
      Hypertrophic Pachymeningitis.
AB  - A forty- seven-year-old man presented with chronic headache with lower cranial
      nerve palsies of ten year duration with recent aggravation of symptoms. MRI
      revealed hypointensity - predominantly of the posterior falx cerebri and the
      tentorium cerebelli - on all sequences with intense peripheral contrast
      enhancement on CE SE T1, which on coronal images mimicked the illuminated Eiffel
      tower by night. 

PMID- 24299644
TI  - Giant prolactinoma mimicking bone tumor.
AB  - Prolactinomas are the most common of the hormone-secreting pituitary tumours.
      Most of them are small in size <10 mm (microprolactinomas) and few are >10 mm
      (macroprolactinomas). It is well known that clinical presentations of
      prolactinomas are quite different between genders (4,5). The vast majority (95%)
      of prolactinomas in women are microadenomas which present with the clinical
      manifestations of hyperprolactinaemia. In contrast, men with prolactinomas often
      present because of symptoms due to the size of the tumour rather than impotence,
      loss of libido or infertility (1,3). Giant pituitary tumours (larger than 4 cm)
      are rare and most of them are nonfunctional. Giant prolactinomas with massive
      extrasellar extension are also rare and their clinical management is sometimes
      problematic. Radiological examinations are of great value in tumour evaluation. 

PMID- 24299645
TI  - Transalar sphenoidal encephalocele. A case report.
AB  - Classification of cranial encephalocele is based on the anatomic location of the
      skull defect. Basal sphenoidal encephaloceles are the least common form of
      encephalocele whose pathogenesis can be congenital, traumatic, tumoral or
      spontaneous. We present a case of a very rare basal encephalocele protruding
      through a defect in the greater wing of the sphenoid bone into the pterygoid
      fossa. 

PMID- 24299646
TI  - Osteogenic Sarcomatous Degeneration of the Temporal Bone Squama in Paget's
      Disease. A Case Report.
AB  - Paget's bone disease is a common disorder affecting approximately 3-4% of the
      population over 40 and up to 10-11% of the population older than 80 years. It is
      characterized by excessive and abnormal bone remodelling. The disease
      predominates in bones containing red marrow, with a clinical course characterized
      by active and quiescent periods; pelvis, sacrum, spine and skull are the most
      affected parts. We report the case of a 79-year-old woman with polyostotic
      Paget's disease who had a focal sarcomatous degeneration diagnosed by CT and MR. 

PMID- 24299647
TI  - Biomechanics of the Spine III. The Cranio-Cervical Junction.
AB  - By virtue of its unique anatomy and functions the cranial-cervical junction was
      excluded in previous reviews on the general biomechanics of the spine, being a
      world apart. The special design of the cranial-cervical (CCJ) junction responds
      to seemingly opposed necessities being at same time loose enough to allow a great
      variety of movements and strong enough to preserve the spinal cord and vertebral
      arteries and to resist the head weight and muscular action. The primary goal of
      the CCJ is to ensure the maximal mobility of the head for visual and auditory
      exploration of space. Like a cardan joint the CCJ allows simultaneous independent
      movements about three axes in order to repeat and extend eye movements under the
      control of vestibular receptors. Several muscular groups and a number of
      ligaments control the movements of the CCJ and ensure its stability. Although
      composed of two seemingly distinct joints the CCJ forms a unique functional
      complex whose stability is ensured by ligaments and bony restraints often
      operating on both joint components: the occipitoatlantal and atlantoaxial joints.

PMID- 24299648
TI  - Thalamic changes in mesial temporal sclerosis: a limbic system pathology. A case
      report.
AB  - Hippocampal abnormalities correlated with mesial temporal sclerosis (MTS) are
      well documented. MTS may be associated with extrahippocampal anomalies involving
      limbic structures along a known neuroanatomic pathway (Papez circuit). We report
      a patient with MTS and thalamic changes. Seizure-related thalamic damage could
      have been caused by abnormal electric discharges from the mamillary body to the
      anterior thalamus through the mamillothalamic tract. This suggests that MTS is
      not limited to the temporal lobe but could represent a limbic system pathology. 

PMID- 24299649
TI  - Spontaneous subdural hematoma in the setting of immune thrombocytopenia
      complicated by ischemic infarcts.
AB  - The occurrence of spontaneous subdural hematoma (SDH) in immune thrombocytopenia
      (ITP) is rare. We report a spontaneous subacute subdural hematoma in a patient
      with chronic ITP. The patient presented with headache and a noncontrast head CT
      scan showed an 11 mm subacute right frontoparietal SDH causing an 8 mm right to
      left midline shift. The patient underwent medical management with platelets, FFP
      and packed RBC transfusions, steroids, IVIG and mannitol, which failed to prevent
      deterioration of her clinical condition. The patient then underwent burr hole
      drainage of the SDH. Her postoperative course was complicated by ischemic
      infarcts in the right posterior cerebral artery territory leaving her with a
      residual left homonymous hemianopia. Our patient was unique in the concurrent
      development of ischemic infarcts postoperatively, following burr hole drainage of
      the SDH in the setting of ITP. This case highlights the diagnostic and
      therapeutic dilemmas involved in taking care of such patients. 

PMID- 24299650
TI  - Ossified posterior longitudinal ligament with an atypical clinical presentation
      in an Indian male. A case report.
AB  - Ossification of the posterior longitudinal ligament is an uncommon disorder
      mostly seen in the Japanese population and hence termed by some the "Japanese
      disease". Ossification of the posterior longitudinal ligament is more common in
      the cervical spine (2). Clinically it is usually asymptomatic, but serious
      neurological deficits have been seen in some patients (2). The ossified mass
      composed of lamellar bone and focal calcified cartilage expands in volume causing
      spinal canal stenosis and cord compression. Morphologically, four forms of
      ossification of the posterior longitudinal ligament have been described:
      continuous, segmental, mixed and rarely a focal retrodiscal form (4). CT scan is
      the method of choice for detecting the presence and extent of the ossified mass.
      MR imaging is helpful in depicting the nature of cord compression such as
      myelomalacia, edema, demyelination or cyst formation and root sleeve involvement.

PMID- 24299651
TI  - Behcet's Disease Presenting with Acute Transverse Myelitis: MRI Findings and
      Review of the Nosology. A Case Report.
AB  - Spinal cord involvement, either isolated or together with brain, in Behcet's
      disease (BD) has been reported. In these cases the existence of the disease was
      previously known or the classical triad of disease such as oral and genital
      ulcers with uveitis/iritis was present. Here we describe a 22-year-old man in
      whom acute transverse myelitis diagnosed with MRI was the first finding of BD. 

PMID- 24299652
TI  - Endovascular treatment of intracranial giant serpentine aneurysms.
AB  - Giant serpentine aneurysms have recently been successfully treated with
      endovascular parent artery occlusion with or without distal by-pass. This report
      retrospectively analyses the outcome of endovascular parent artery occlusion for
      intracranial giant serpentine aneurysms. Medical records and cerebral angiograms
      from our endovascular center were analyzed retrospectively. Five patients with
      serpentine aneurysms were treated by endovascular occlusion of the parent artery
      at the site of the aneurysm. These patients had selective treatment. The clinical
      and angiographic outcomes in five patients were assessed at three months to three
      years. No cerebral infarction occurred. Of the patients, five made excellent
      recoveries at follow-up. No recurrence or rebleeding was noted. Endovascular
      parent artery occlusion may be a safe and effective way to treat intracranial
      giant serpentine aneurysms. 

PMID- 24299653
TI  - Anterior medial transoral c2 vertebroplasty. A case report.
AB  - We present the case of a 63-year-old man with a C2 metastasis and a life
      expectancy of a few months who was independent at the time of diagnosis. In
      accordance with oncologists and radiotherapists, under antibiotic prophylaxis and
      general anesthesia, C2 vertebroplasty with an anterior medial transoral approach
      was performed, followed by radiotherapy. A satisfactory clinical result was
      obtained consisting in pain relief and avoidance of progression to vertebral
      collapse and spinal cord compression. We suggest that vertebroplasty should be
      performed even in compromised patients with a short life expectancy with a C2
      metastasis difficult to access from a technical point of view. 

PMID- 24299654
TI  - The Effect of Implant Angulation on the Transfer Accuracy of External-Connection
      Implants.
AB  - BACKGROUND: Accurate recording of implant location is required in every implant
      supported prostheses. Implant angulation, which is inevitable in various clinical
      situations, could affect the impression accuracy. PURPOSE: The purpose of this in
      vitro study was to compare the transfer accuracy of straight and tilted implants
      of All-on-4 protocol with implant or abutment level impression making and
      different techniques of direct and indirect. MATERIALS AND METHODS: One reference
      model of edentulous maxilla with four external connection implants (Branemark)
      inserted according to All-on-4 protocol was made. Forty impressions of this model
      were made at implant (groups 1 and 2) or abutment (groups 3 and 4) levels with
      different techniques of direct or indirect, respectively. Impressions were poured
      with type IV dental stone. Coordinate measuring machine was used to record x, y,
      and z coordinates and also angular dislocation of implants. These measurements
      were compared with the equals calculated on the reference model. Data were
      analyzed with univariate analysis of variance and t-test at alpha = 0.05.
      RESULTS: The results showed that abutment level impression making (groups 3 and
      4), either with direct or indirect technique, produced the same results for
      straight and tilted implants of Deltar variable (p > .05), though in implant
      level groups (groups 1 and 2), it was statistically significant (p < .05).
      However, only implant level impression making with direct technique (group 1) had
      the same results of angular accuracy for straight and tilted implants.
      CONCLUSION: Impression technique (direct or indirect) had significant effect on
      the impression accuracy of tilted implants, and direct technique produced less
      inaccuracy. Also, abutment level impressions showed more accuracy than implant
      level impressions.

PMID- 24299655
TI  - Revisiting whitlockite, the second most abundant biomineral in bone: nanocrystal
      synthesis in physiologically relevant conditions and biocompatibility evaluation.
AB  - The synthesis of pure whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) has remained a
      challenge even though it is the second most abundant inorganic in living bone.
      Although a few reports about the precipitation of WH in heterogeneous phases have
      been published, to date, synthesizing WH without utilizing any effects of a
      buffer or various other ions remains difficult. Thus, the related research fields
      have encountered difficulties and have not been fully developed. Here, we
      developed a large-scale synthesis method for pure WH nanoparticles in a ternary
      Ca(OH)2-Mg(OH)2-H3PO4 system based on a systematic approach. We used excess
      Mg(2+) to impede the growth of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and the
      formation of other kinetically favored calcium phosphate intermediate phases. In
      addition, we designed and investigated the synthesis conditions of WH under the
      acidic pH conditions required to dissolve HAP, which is the most
      thermodynamically stable phase above pH 4.2, and to incorporate the HPO4(2-)
      group into the chemical structure of WH. We demonstrated that pure WH
      nanoparticles can be precipitated under Mg(2+)-rich and acidic pH conditions
      without any intermediate phases. Interestingly, this synthesized nano-WH showed
      comparable biocompatibility with HAP. Our methodology for determining the
      synthesis conditions of WH could provide a new platform for investigating other
      important precipitants in aqueous systems. 

PMID- 24299656
TI  - Hospital discharge: results from an Italian multicenter prospective study using
      Blaylock Risk Assessment Screening Score.
AB  - PURPOSE: To analyze the predictive validity and reliability of the Blaylock Risk
      Assessment Screening Score (BRASS) Index in a large group of patients. METHODS:
      Prospective multicenter observational study was conducted in six Italian
      hospitals. Data were collected in three phases. FINDINGS: Seven hundred eleven
      patients were recruited. The mean length of hospitalization for low-risk patients
      was significantly shorter than those in the medium and high-risk groups. Patients
      with a BRASS Index lower than 10, unlike those with a higher BRASS Index, were
      mainly discharged home. CONCLUSIONS: Our results indicate that the BRASS Index is
      useful to identify patients at risk for prolonged hospitalization. CLINICAL
      RELEVANCE: The use of a validated BRASS instrument can be useful to screen the
      patients, improving individual discharge planning.

PMID- 24299657
TI  - A systematic review and meta-analysis of naltrexone implants for the treatment of
      opioid dependence.
AB  - INTRODUCTION AND AIMS: Naltrexone implants are used to treat opioid dependence,
      but their safety and efficacy remain poorly understood. We systematically
      reviewed the literature to assess the safety and efficacy of naltrexone implants
      for treating opioid dependence. DESIGN AND METHODS: Studies were eligible if they
      compared naltrexone implants with another intervention or placebo. Examined
      outcomes were induction to treatment, retention in treatment, opioid and non
      opioid use, adverse events, non-fatal overdose and mortality. Quality of the
      evidence was assessed using the Grading of Recommendations Assessment,
      Development, and Evaluation approach. Data from randomised studies were combined
      using meta-analysis. Data from non-randomised studies were presented narratively.
      RESULTS: Five randomised trials (n = 576) and four non-randomised studies (n =
      8358) were eligible for review. The quality of the evidence ranged from moderate
      to very low. Naltrexone implants were superior to placebo implants [risk ratio
      (RR): 0.57; 95% confidence interval (CI) 0.48, 0.68; k = 2] and oral naltrexone
      (RR: 0.57; 95% CI 0.47, 0.70; k = 2) in suppressing opioid use. No difference in
      opioid use was observed between naltrexone implants and methadone maintenance
      (standardised mean difference: -0.33; 95% CI -0.93, 0.26; k = 1); however, this
      finding was based on low-quality evidence from one study. DISCUSSION: The
      evidence on safety and efficacy of naltrexone implants is limited in quantity and
      quality, and the evidence has little clinical utility in settings where effective
      treatments for opioid dependence are used. CONCLUSION: Better designed research
      is needed to establish the safety and efficacy of naltrexone implants. Until such
      time, their use should be limited to clinical trials. [Larney S, Gowing L,
      Mattick RP, Farrell M, Hall W, Degenhardt L. A systematic review and meta
      analysis of naltrexone implants for the treatment of opioid dependence.

PMID- 24299658
TI  - Ocean acidification and fertilization in the antarctic sea urchin Sterechinus
      neumayeri: the importance of polyspermy.
AB  - Ocean acidification (OA), the reduction of the seawater pH as a result of
      increasing levels of atmospheric CO2, is an important climate change stressor in
      the Southern Ocean and Antarctic. We examined the impact of OA on fertilization
      success in the Antarctic sea urchin Sterechinus neumayeri using pH treatment
      conditions reflective of the current and near-future "pH seascape" for this
      species: current (control: pH 8.052, 384.1 MUatm of pCO2), a high CO2 treatment
      approximating the 0.2-0.3 unit decrease in pH predicted for 2100 (high CO2: pH
      7.830, 666.0 MUatm of pCO2), and an intermediate medium CO2 (pH 7.967, 473.4
      MUatm of pCO2). Using a fertilization kinetics approach and mixed-effect models,
      we observed significant variation in the OA response between individual
      male/female pairs (N = 7) and a significant population-level increase (70-100%)
      in tb (time for a complete block to polyspermy) at medium and high CO2, a
      mechanism that potentially explains the higher levels of abnormal development
      seen in OA conditions. However, two pairs showed higher fertilization success
      with CO2 treatment and a nonsignificant effect. Future studies should focus on
      the mechanisms and levels of interindividual variability in OA response, so that
      we can consider the potential for selection and adaptation of organisms to a
      future ocean. 

PMID- 24299659
TI  - Dynamics of the concentration of IAA and some of its conjugates during the
      induction of somatic embryogenesis in Coffea canephora.
AB  - Most of the somatic embryogenesis (SE) process requires the presence, either
      before or during the embryogenic process, of at least one exogenous auxin. This
      exogenous auxin induces the presence of endogenous auxins, which appears to be
      essential for SE induction. We found that during the preincubation period of SE
      in Coffea canephora, there is an important increase in both free and conjugated
      indole-3-acetic acid (IAA), as well as indole-3-butyric acid. This increase is
      accompanied by an increase in the expression of YUCCA (CcYUC), TRYPTOPHAN
      AMINOTRANSFERASE OF ARABIDOPSIS 1 (CcTAA1), and GRETCHEN HAGEN 3 (GH3) genes. On
      the other hand, most of the IAA compounds decreased during the induction of SE.
      The results presented in this research suggest that a balance between free IAA
      and its amide conjugates is necessary to allow the expression of SE-related
      genes. 

PMID- 24299660
TI  - Fluid homeostasis in the neonate.
AB  - The physiology of the neonate is ideally suited to the transition to extrauterine
      life followed by a period of rapid growth and development. Intravenous fluids and
      electrolytes should be prescribed with care in the neonate. Sodium and water
      requirements in the first few days of life are low and should be increased after
      the postnatal diuresis. Expansion of the extracellular fluid volume prior to the
      postnatal diuresis is associated with poor outcomes, particularly in preterm
      infants. Newborn infants are prone to hypoglycemia and require a source of
      intravenous glucose if enteral feeds are withheld. Anemia is common, and
      untreated is associated with poor outcomes. Liberal versus restrictive
      transfusion practices are controversial, but liberal transfusion practices
      (accompanied by measures to minimize donor exposure) may be associated with
      improved long-term outcomes. Intravenous crystalloids are as effective as albumin
      to treat hypotension, and semi-synthetic colloids cannot be recommended at this
      time. Inotropes should be used to treat hypotension unresponsive to intravenous
      fluid, ideally guided by assessment of perfusion rather than blood pressure
      alone. Noninvasive methods of assessing cardiac output have been validated in
      neonates. More studies are required to guide fluid management in neonates,
      particularly in those with sepsis or undergoing surgery. A balanced salt solution
      such as Hartmann's or Plasmalyte should be used to replace losses during surgery
      (and blood or coagulation factors as indicated). Excessive fluid administration
      during surgery should be avoided. 

PMID- 24299661
TI  - Use of a variable-index fractional-derivative model to capture transient
      dispersion in heterogeneous media.
AB  - Field and numerical experiments of solute transport through heterogeneous porous
      and fractured media show that the growth of contaminant plumes may not exhibit
      constant scaling, and may instead transition between diffusive states (i.e.,
      superdiffusion, subdiffusion, and Fickian diffusion) at various transport scales.
      These transitions are likely attributed to physical properties of the medium,
      such as spatial variations in medium heterogeneity. We refer to this transitory
      dispersive behavior as "transient dispersion", and propose a variable-index
      fractional-derivative model (FDM) to describe the underlying transport dynamics.
      The new model generalizes the standard constant-index FDM which is limited to
      stationary heterogeneous media. Numerical methods including an implicit Eulerian
      method (for spatiotemporal transient dispersion) and a Lagrangian solver (for
      multiscaling dispersion) are utilized to produce variable-index FDM solutions.
      The variable-index FDM is then applied to describe transient dispersion observed
      at two field tracer tests and a set of numerical experiments. Results show that
      1) uranine transport at the small-scale Grimsel test site transitions from strong
      subdispersion to Fickian dispersion, 2) transport of tritium at the regional
      scale Macrodispersion Experimental (MADE) site transitions from near-Fickian
      dispersion to strong superdispersion, and 3) the conservative particle transport
      through regional-scale discrete fracture network transitions from superdispersion
      to Fickian dispersion. The variable-index model can efficiently quantify these
      transitions, with the scale index varying linearly in time or space. 

PMID- 24299663
TI  - Parasagittal Arachnoid Markings on the Inner Skull on Three-Dimensional CT:
      Relation between Hydrocephalus and Arachnoid Granules.
AB  - The purpose of the study was to evaluate the number and size of arachnoid
      markings on the inner plate of the skull on 3D-CT. The subjects included 16
      hydrocephalus and 26 non-hydrocephalus cases. We evaluated the correlation
      between age and both the number and sizes of the arachnoid markings, and compared
      them between hydrocephalus and non-hydrocephalus cases. We also evaluated cases
      exhibiting a "smooth cranium" that had no arachnoid markings at all on the inner
      plate. There was a positive correlation between age and the number of the
      arachnoid markings. There were no statistically significant differences in
      arachnoid markings between hydrocephalus and non-hydrocephalus cases, while,
      there were statistically significant differences in the frequency of "smooth
      cranium" findings in the population under ten years old. The "smooth cranium" can
      only be seen in hydrocephalus cases. These findings may be a clue to the
      morphological or functional changes of the arachnoid villi in hydrocephalus
      cases. 

PMID- 24299662
TI  - Effects of dietary supplementation with epigallocatechin-3-gallate on weight
      loss, energy homeostasis, cardiometabolic risk factors and liver function in
      obese women: randomised, double-blind, placebo-controlled clinical trial.
AB  - The aim of the present study was to examine the effects of green tea
      epigallocatechin-3-gallate (EGCG) on changes in body composition, energy and
      substrate metabolism, cardiometabolic risk factors and liver function enzymes
      after an energy-restricted diet intervention in obese women. In the present
      randomised, double-blind, placebo-controlled study, eighty-three obese (30 kg/m2
      > BMI < 40 kg/m2) pre-menopausal women consumed 300 mg/d of EGCG or placebo
      (lactose). We measured body weight and adiposity (dual-energy X-ray
      absorptiometry), energy expenditure and fat oxidation rates (indirect
      calorimetry), blood lipid levels (TAG, total cholesterol, LDL-cholesterol and HDL
      cholesterol), insulin resistance, C-reactive protein and liver function markers
      (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
      gamma-glutamyltransferase, urea, bilirubin and 2-keto[1-13C]isocaproate
      oxidation) before and after the intervention in the EGCG and control groups. We
      did not find any significant difference in the changes in body weight (-0.3 kg,
      95% CI -5.0, 4.3), fat mass (-0.7 kg, 95% CI -3.5, 2.1), energy (0.3 kJ/kg per d,
      95% CI -3.1, 2.7) and fat (-0.1 g/min, 95% CI -0.03, 0.01) metabolism,
      homeostasis assessment model for insulin resistance (0.2, 95% CI -0.2, 0.7),
      total cholesterol (-0.21 mmol/l, 95% CI -0.55, 0.13), LDL-cholesterol (-0.15
      mmol/l, 95% CI -0.50, 0.20), TAG (-0.4 mmol/l, 95% CI -0.56, 0.29) and liver
      function markers between the EGCG and control groups. In conclusion, the present
      results suggest that dietary supplementation with 300 mg/d of EGCG for 12 weeks
      did not enhance energy-restricted diet-induced adiposity reductions, and did not
      improve weight-loss-induced changes in cardiometabolic risk factors in obese
      Caucasian women. The intake of 300 mg/d of EGCG for 12 weeks did not cause any
      adverse effect on liver function biomarkers.

PMID- 24299664
TI  - Middle cerebral artery occlusion causing intracerebral hemorrhage: radiologic
      findings.
AB  - Middle cerebral artery (MCA) occlusion usually leads to cerebral infarction but
      rarely causes cerebral hemorrhage without infarction. We retrospectively
      investigated the unique radiographic manifestations in cases of cerebral
      hemorrhage without infarction. Computed tomography (CT) and angiographic images
      obtained in four patients (aged 26 to 70 years) with MCA occlusion associated
      with intracerebral hemorrhage were reviewed. Two patients also underwent magnetic
      resonance imaging (MRI), and one of these underwent magnetic resonance
      angiography as well; these images were also examined. Cranial CT revealed
      periventricular hemorrhage with ventricular penetration in one patient and with
      putaminal penetration in two. Solitary ventricular hemorrhage was found in the
      fourth patient. Angiography showed ipsilateral occlusion at the M1 portion of the
      MCA, accompanied by moyamoya-like vessels. No aneurysm or arteriovenous
      malformation was detected. MRI showed absence of the flow void in the affected
      MCA and an abnormal flow void in dilated collateral vessels in the basal ganglia.
      MCA occlusion can cause periventricular or ventricular hemorrhage, which appears
      to result from bleeding from fragile dilated collateral vessels and, thus, to
      have an etiology similar to that of adult moyamoya disease. MRI shows promise as
      a tool for evaluating the occlusion site. 

PMID- 24299665
TI  - Mitochondrial Leukodystrophy: an Unusual Manifestation of Leigh's Disease. A
      Report of Three Cases and Review of the Literature.
AB  - Leigh's disease is an inherited, progressive neurodegenerative disorder of
      infancy and early childhood. This metabolic disease is biochemically and
      genetically a heterogeneous disorder with defects involving various enzymes
      involved in the respiratory chain mechanism. Due to the multitude of enzyme
      defects known to occur in patients afflicted with Leigh's disease, this condition
      is known to have a variable clinical, pathological and radiological pattern of
      presentation. Isolated deficiency of cytochrome oxidase (COX) enzyme is one of
      the commonest abnormalities seen in patients afflicted by Leigh's disease. A
      primary white matter pattern of involvement representing a mitochondrial
      leukodystrophy is rare. Symmetric hyperintensities on T2WI involving the
      subthalamic nuclei and brainstem have been reported in patients with COX
      deficiency with SURF 1 mutations and are considered almost a hallmark of Leigh's
      disease with COX deficiency. We describe three cases of Leigh's disease with a
      primary white matter involvement diagnosed at our institution on the basis of
      clinical features, radiological appearance and laboratory findings. 

PMID- 24299666
TI  - MR Spectroscopy Findings in Lhermitte-Duclos Disease. A Case Report.
AB  - Lhermitte-Duclos disease (LDD) is a rare hamartomatous focal or diffuse
      enlargement of the cerebellum with unclear etiology. The characteristic magnetic
      resonance imaging (MRI) appearance consists of a non-enhancing mass in the
      cerebellar hemisphere with a striated pattern. The slow growing behavior of this
      benign lesion is characteristic. In a few reports on magnetic resonance
      spectroscopy (MRS) findings in LDD, a decreased level of N-acetyl aspartate,
      increased level of lactate and near normal level of choline were described. The
      information obtained from MRS is useful to confirm the relatively benign
      hamartomatous nature of the lesion. This paper reports a case of LDD and
      describes the MRI and MRS findings. 

PMID- 24299667
TI  - Diffusion weighted MRI of primary pituitary abscess. Case report.
AB  - Pituitary abscess is a rarely seen entity that can lead to serious neuroendocrine
      disorders or even be fatal if not diagnosed or treated correctly. Preoperative
      diagnosis plays an important role in planning the operation and treatment
      strategies. This report describes the diagnostic value of diffusion-weighted
      imaging (DWI) in addition to conventional magnetic resonance imaging (MRI) of
      primary pituitary abscess formation caused by Klebsiella ozaenea in a 33-year-old
      man. 

PMID- 24299668
TI  - Recurrent Cerebral Fat Embolism Due to Pleural Irrigation: Fat Density Lesions on
      CT. A Case Report.
AB  - Fat embolism syndrome is a rare, but life-threatening problem and is usually
      associated with severe trauma. Neurological symptoms are variable, and the
      clinical diagnosis is difficult. We describe a patient with fat density lesions
      on cranial CT sections and discuss the etiopathogenesis of cerebral fat embolism
      (CFE) in this patient who does not have a history of long bone fracture, but
      metastatic lung disease and empyema. This is probably the first case report of
      CFE secondary to pleural irrigation of empyema with demonstrative CT findings. 

PMID- 24299669
TI  - Spontaneous resolution of bilateral superior ophthalmic vein and cavernous sinus
      thrombosis. A case report.
AB  - Superior ophthalmic vein thrombosis is uncommon, and bilateral superior
      ophthalmic vein thrombosis is rarer still. The resolution of bilateral superior
      ophthalmic vein thrombosis takes a long time. The spontaneous resolution of
      bilateral superior ophthalmic vein thrombosis is not known and not reported in
      the literature so far. Here we present MRI of bilateral superior ophthalmic vein
      thrombosis and its spontaneous resolution. 

PMID- 24299670
TI  - Evaluation of an Intracranial Arteriovenous Malformation by Multi-Detector CT
      Angiography. A Case Report.
AB  - Intracranial arteriovenous malformations are congenital vascular lesions
      characterized by localized arteriovenous shunting. Digital subtraction
      angiography is the gold standard for diagnosis. We herein report a case of
      intracranial arteriovenous malformations diagnosed by multi-detector computed
      tomographic (MDCT) angiography. The findings of MDCT angiography were confirmed
      by digital subtraction angiography. CT angiography might be a useful first-line
      screening tool, especially in an emergency situation. 

PMID- 24299671
TI  - Cerebral infarction due to vasoconstriction after a hymenoptera stin.
AB  - A 22-year-old woman developed an anaphylactic reaction after two hornet stings.
      Left-sided hemiparesis and gaze paresis were revealed after extubation 24 hours
      later. The vasoconstriction of the right MCA together with hypotension are the
      suggested pathogenetic determinants of the stroke. 

PMID- 24299672
TI  - Giant mesencephalothalamic virchow-robin spaces causing obstructive
      hydrocephalus. A case report.
AB  - Virchow-Robin spaces accompany arteries for a variable distance into the brain
      substance. They are usually small but can be identified on high resolution MRI
      images in patients of all age groups. We report a rare case of a 40-year-old
      woman with giant mesencephalothalamic Virchow-Robin spaces which caused
      hydrocephalus requiring CSF diversion. After right ventriculoperitoneal shunt the
      patient recovered completely. 

PMID- 24299673
TI  - Lhermitte-duclos disease with syringomyelia. A report of two cases.
AB  - Dysplastic gangliocytoma is defined as a rare cerebellar mass lesion with
      malformative, hamartomatous and neoplastic features, arising from cerebellar
      neurons and affecting the population in early adulthood. Common clinical
      presentation is in the form of headache, features of raised intracranial tension
      or hydrocephalus. It may also be found as an incidental lesion. Even though many
      cases of this disease entity have been reported in literature, its association
      with syrinx is less commonly highlighted and hence we are reporting these two
      cases which we encountered at our institute. Presence of an associated syrinx
      should not deter one to make a preoperative diagnosis of this condition once the
      striking imaging findings are visualized. 

PMID- 24299674
TI  - MR Myelography in Degenerative Spinal Disease.
AB  - This study aimed to establish the possible role of magnetic resonance myelography
      in degenerative spinal disease. A high magnetic field strength MR system is
      required for this technique with a high slew rate and expertise in standard MR
      techniques. MR myelography is obtained by a strongly T2-weighted TSE sequence
      with suppression of the signal from stationary tissues and adipose tissue. The
      data obtained are processed using the MIP algorithm. Between April 2004 and July
      2006, 278 patients were examined. Of these, 47 were negative, 210 had herniated
      discs, 16 had tumours, four had synovial cysts and one had traumatic cervical
      nerve root avulsion. 163 patients with degenerative disease underwent surgery
      which confirmed the MR examination with the myelographic sequence. Our findings
      show that MR myelography is useful in neuroradiological diagnosis, namely in
      patients lacking exhaustive CT or MR documentation of their severe clinical
      symptoms. 

PMID- 24299675
TI  - Double stenting procedure and coil embolization in a patient with carotid
      stenosis and incidental ipsilateral intracranial aneurysm. A case report and
      dosimetric evaluation.
AB  - We describe a case of incidental detection of an intracranial left ICA wide
      necked aneurysm during digital subtraction angiography performed to assess a sub
      occlusive and calcified stenosis in the extracranial portion of the same artery.
      Angioplasty and stenting of ICA stenosis, plus intracranial stent deployment
      across the aneurysm neck was performed during the same procedure. Aneurysm coil
      embolization was postponed to a further session one month later. The radiation
      dose and irradiated areas were also evaluated during endovascular procedures. 

PMID- 24299676
TI  - Acute Ruptured Intracranial Aneurysm Packing with HydroCoil Embolic System:
      Initial Clinical Experience.
AB  - The HydroCoil Embolic System (HES; MicroVention, Aliso Viejo, CA, USA) was
      developed to improve the efficacy of endovascular treatment of cerebral
      aneurysms. The HES may reduce recurrences of aneurysms by allowing for increased
      packing density compared with platinum coils. We report our initial experience
      with the HES in the treatment of 31 patients with acute ruptured cerebral
      aneurysms. The HES is another safe and effective material for aneurysms
      embolization, which provided substantially improved volumetric packing of the
      aneurysm lumen. 

PMID- 24299677
TI  - Treatment with double neuroform2 stent deployment of a ruptured fusiform internal
      carotid artery aneurysm. A case report.
AB  - The Neuroform stent is the first microcatheter delivered stent designed
      specifically for the treatment of cerebral aneurysms. Recently, some reports on
      unconventional uses of the Neuroform stent have provided intelligent technical
      solutions to difficult endovascular cases. A 43-year-old man presented with
      severe headache. Imaging studies revealed subarachnoid hemorrhage and a fusiform
      vessel dilatation with a small aneurysm arising from the communicating segment of
      the left internal carotid artery. We report here the case of a double Neuroform2
      stent without coiling within a ruptured fusiform aneurysm of the internal carotid
      artery. 

PMID- 24299678
TI  - Stenting and coil embolization of a surgically treated residual aneurysm of the
      middle cerebral artery bifurcation associated with coil embolization of a
      communicating artery aneurysm. A case report.
AB  - We describe the case of a 76-year-old man admitted to our hospital for mild
      subarachnoid haemorrhage detected by CT scan in an aneurysm of the left middle
      cerebral artery bifurcation treated surgically 29 years earlier and not
      completely occluded. Angiography disclosed a further aneurysm in the anterior
      communicating artery. During the same procedure we treated the residual aneurysm
      in the left middle cerebral artery bifurcation positioning a Neuroform3 stent
      (Boston) and embolization deploying two biologically active Cerecyte coils (Balt)
      for a total of 10 cm and excluding the communicating artery aneurysm from the
      circulation releasing two active Cerecyte coils for a total length of 30.9 cm.
      The procedure was well tolerated by the patient and did not give rise to
      neurological deficits. 

PMID- 24299679
TI  - Transvenous embolization of cavernous sinus dural arteriovenous fistula with onyx
      18 and platinum coils. A technical note.
AB  - We describe a patient with dural arterial venous fistula of the cavernous sinus
      causing occulomotor palsy and chemosis. The fistula was successfully treated via
      transvenous approach with Onyx-18 and detachable platinum coils. 

PMID- 24299680
TI  - Transarterial embolization of dural arteriovenous fistulas of the anterior
      cranial fossa using onyx-18. A case report.
AB  - We describe the first case of a dural arteriovenous fistula of the anterior
      cranial fossa successfully treated with transarterial embolization using Onyx-18.

PMID- 24299681
TI  - Percutaneous closure after inadvertent carotid artery cannulation. Puncture
      repair with angio-seal deployment. A case report.
AB  - Inadvertent placement of an introducer sheath in an artery during central venous
      cannulation is rare and can result in devastating complications. Although
      traditional closure devices have been employed as prompt and adequate treatment,
      more innovative devices such as collagen plugs are being studied for their
      efficacy. We report a case of inadvertent insertion of an 8 French sheath into
      the right carotid artery which occurred in the electrophysiological laboratory
      during scheduled transjugular measurement of portal pressure gradient. The
      consultant neuroradiologist successfully removed the arterial sheath and the
      puncture site was sealed with a collagen-based vascular closure device (Angio
      Seal STS Plus). Accidental insertion of an arterial sheath is an uncommon but
      potentially serious complication of jugular venous catheterization. When the
      carotid artery is inadvertently cannulated, sheath removal can be complicated by
      significant hemorrhage and acute dyspnea due to location of the vessel near the
      upper airways. Although traditional manual compression and closure devices have
      been effective at restoring hemostasis, collagen seals or plugs may be more
      viable to treat this precarious situation. This averted an otherwise emergent
      open surgical procedure to remove the sheath and repair the carotid artery in a
      high-risk patient. 

PMID- 24299682
TI  - Craniospinal involvement in a patient with isolated bone marrow mastocytosis. A
      case report.
AB  - Central nervous system involvement in systemic mastocytosis (SM) is very rare.
      This case report describes the computed tomography and magnetic resonance (MR)
      imaging findings of central nervous system involvement in a patient with isolated
      bone marrow mastocystosis. Bone marrow infiltration in SM caused cranial nerve
      dysfunction and meningeal irritation secondary to narrowing of cranial apertures
      and meningeal involvement, respectively. MR imaging is the modality of choice in
      both detection and follow-up of SM and also useful for differential diagnosis and
      detection of complications. 

PMID- 24299683
TI  - Treacher-collins syndrome and associated abnormalities. A case report.
AB  - Treacher-Collins syndrome or mandibulofacial dysostosis is an autosomal dominant
      disorder of craniofacial development. In this familial syndrome there is an
      arrest in the development of the facial bones, manifested by a depression of the
      malar bones, an antimonogoloid slant of the palpebral fissures, mandibular
      hypoplasia with retrognathia, coloboma of the lower eyelids and deformities of
      the ear structures derived from the branchial arches. Frequently, there is
      external auditory canal atresia and deformity of the pinnae. Other uncommon
      anomalies include congenital heart defects and cryptorchidism. This study
      describes a rare case of Treacher-Collins syndrome associated with congenital
      cardiopathy and megacolon, with a review of the literature. 

PMID- 24299684
TI  - Polyostotic Paget's Disease with Sarcomatous Change in a Skull Lesion. A Case
      Report of Imaging Findings.
AB  - The most serious complication of Paget's disease is sarcomatous degeneration of
      pagetic bone. Multifocal sarcomatous degeneration occurs mainly in polyostotic
      Paget's disease. Paget sarcomas are the most threatening sarcomas of bone
      irrespective of the histopathology, their prognosis being far more negative than
      primary sarcomas. Paget's disease is a common entity but osteosarcoma arising in
      Paget's disease is an infrequent complication. The skull involvement is even
      rarer. We report a case of malignant transformation of a skull lesion in a
      patient of polyostotic Paget's disease. Skull radiographs, computed tomography
      and magnetic resonance imaging scans of the tumour area show interesting results.

PMID- 24299685
TI  - Castleman's Disease: Unilateral Cervical Involvement and Imaging Findings. A Case
      Report.
AB  - Castleman's disease is an idiopathic lymphoproliferative disorder characterized
      by massive enlargement of lymph nodes. It may have a unifocal or multifocal
      presentation; the mediastinum is the most common site (70%). Patients with
      cervical disease usually have unifocal involvement (90%). The main problem posed
      by cervical Castleman's disease is that it should be considered in the
      differential diagnosis of cervical tumors. This report describes a patient who
      had unifocal Castleman's disease on the left side of the neck, and discusses the
      differential diagnosis with findings on magnetic resonance imaging, computed
      tomography and ultrasonography. 

PMID- 24299686
TI  - When and why portal vein thrombosis matters in liver transplantation: a critical
      audit of 174 cases.
AB  - OBJECTIVE: To identify complications associated with different techniques
      utilized to treat portal vein thrombosis (PVT) during primary liver
      transplantation and their impact on survival. BACKGROUND: PVT remains an
      intricate problem in liver transplantation, and the long-term outcomes of
      patients with PVT who undergo transplantation are not well defined. METHODS: We
      performed a retrospective cohort analysis of all consecutive adult patients who
      underwent primary isolated liver transplantation from 1998 to 2009 (median follow
      up period, 89 months). The outcomes of patients with PVT were compared with those
      without PVT. RESULTS: Among 1379 recipients, 174 (12.6%) had PVT at the time of
      transplantation [83 (48%) complete and 91 (52%) partial]. Among PVT patients with
      reestablished physiological portal inflow (PVT: physiological group; n = 149),
      123 underwent thrombectomies, 16 received interpositional vein grafts, and 10
      received mesoportal jump grafts. In 25 patients, physiological portomesenteric
      venous circulation was not reconstituted (PVT: nonphysiological group; 18
      underwent cavoportal hemitranspositions, 6 renoportal anastomoses, and 1
      arterialization). The PVT: nonphysiological group suffered a significantly
      increased incidence of rethrombosis of the portomesenteric veins and
      gastrointestinal bleeding, with a marginal 10-year overall survival rate of 42%
      (no PVT, 61%; P = 0.002 and PVT: physiological, 55%; P = 0.043). The PVT:
      physiological and no PVT groups exhibited comparable survival rates (P = 0.13).
      No significant differences in survival were observed between complete and partial
      PVT as long as physiological portal flow was reestablished. CONCLUSIONS: The
      subset of PVT patients requiring nonphysiological portal vein reconstruction was
      associated with higher complication rates and suffered diminished long-term
      prognoses. For the most severe PVT cases, a comprehensive approach is critical to
      further improve outcomes.

PMID- 24299687
TI  - Reply to Letter: "Surgically Induced Neuropathic Pain: Understanding the
      Perioperative Process".

PMID- 24299689
TI  - Exploring issues in difficult-to-treat hypertension.

PMID- 24299688
TI  - The smooth muscle-type beta1 subunit potentiates activation by DiBAC4(3) in
      recombinant BK channels.
AB  - Large-conductance Ca(2+)-activated (BK) channels, expressed in a variety of
      tissues, play a fundamental role in regulating and maintaining arterial tone. We
      recently demonstrated that the slow voltage indicator DiBAC4(3) does not depend,
      as initially proposed, on the beta 1 or beta 4 subunits to activate native
      arterial smooth muscle BK channels. Using recombinant mslo BK channels, we now
      show that the beta 1 subunit is not essential to this activation but exerts a
      large potentiating effect. DiBAC4(3) promotes concentration-dependent activation
      of BK channels and slows deactivation kinetics, changes that are independent of
      Ca(2+). Kd values for BK channel activation by DiBAC4(3) in 0 mM Ca(2+) are
      approximately 20 MUM (alpha) and 5 MUM (alpha+beta 1), and G-V curves shift up to
      -40 mV and -110 mV, respectively. beta1 to beta2 mutations R11A and C18E do not
      interfere with the potentiating effect of the subunit. Our findings should help
      refine the role of the beta 1 subunit in cardiovascular pharmacology.

PMID- 24299690
TI  - Commentary in support of a highly effective hypertension treatment algorithm.
AB  - A simple hypertension treatment algorithm has contributed to the achievement of
      control rates greater than 85% for more than 1 million adults with hypertension
      across the United States. It is built on the fixed-dose combination drug
      lisinopril/hydrochlorothiazide, which is maximized in three steps before adding
      amlodipine. Spironolactone is the preferred fourth drug. 

PMID- 24299691
TI  - Relationship between inter-arm difference in systolic blood pressure and arterial
      stiffness in community-dwelling older adults.
AB  - A significant inter-arm difference in systolic blood pressure (IADSBP) has
      recently been associated with worse cardiovascular outcomes. The authors
      hypothesized that part of this association is mediated by arterial stiffness, and
      examined the relationship between significant IADSBP and carotid-femoral pulse
      wave velocity (CF-PWV) in a sample from the Baltimore Longitudinal Study of
      Aging. Of 1045 participants, 50 (4.8%) had an IADSBP >=10 mm Hg at baseline, and
      629 had completed data from >=2 visits (for a total of 1704 visits during 8
      years). CF-PWV was significantly higher in patients with an IADSBP >=10 mm Hg
      (7.3+/-1.9 vs 8.2+/-2, P=.002). Compared with others, patients with IADSBP >=10
      mm Hg also had higher body mass index, waist circumference, and triglycerides;
      higher prevalence of diabetes; and lower high-density lipoprotein (HDL)
      cholesterol (P<.001 for all). A significant association with IADSBP >=10 mm Hg
      was observed for CF-PWV in both cross-sectional (odds ratio [OR], 1.19; 95%
      confidence interval [CI], 1.06-1.87; P=.01) and longitudinal (OR, 1.15; 95% CI,
      1.03-1.29; P=.01) multivariate analyses. Female sex, Caucasian race, high body
      mass index (plus diabetes and low HDL cholesterol only cross-sectionally) were
      other independent correlates of IADSBP >=10 mm Hg. Significant IADSBP is
      associated with increased arterial stiffness in community-dwelling older adults. 

PMID- 24299692
TI  - Arterial stiffness in patients with peripheral arterial disease.

PMID- 24299693
TI  - Reply to arterial stiffness in patients with peripheral arterial disease.

PMID- 24299694
TI  - Lipid-lowering in African Americans in ALLHAT-optimism bias?

PMID- 24299695
TI  - Author response to lipid-lowering in African Americans in ALLHAT-optimism bias?

PMID- 24299696
TI  - 2014 Update on the 'growing spine surgery' for young children with scoliosis.
AB  - PURPOSE OF REVIEW: Spinal fusion procedures that are the mainstay of the
      treatment of progressive or severe curves in adolescents and adults are not
      suitable for most young children as there is a large magnitude of remaining
      growth. Early spinal fusion stunts the growth of the thorax and may interfere
      with the development of the lungs. Therefore, in children with early-onset
      scoliosis, 'growth friendly' instrumentation systems have been utilized to
      control the deformity while allowing the growth of the spine and the thoracic
      cage. RECENT FINDINGS: The experience with growing rods has been increasing,
      along with expanding indications. Several self-lengthening instrumentation
      systems have been introduced aiming for guided spinal growth. There has been
      considerable progress in the clinical and laboratory studies using magnetically
      controlled growing rod constructs. Growing rods and vertical expandable
      prosthetic titanium rib (VEPTR) systems provide deformity control while allowing
      for spinal growth along with a risk of spontaneous vertebral fusions. VEPTR may
      cause rib fusions as the implants overlie the thoracic cage and, therefore, the
      use in pure spinal deformities is controversial. SUMMARY: There have been
      exciting recent advances concerning the treatment of spinal deformities in young
      children. Despite these advances, the surgical treatment of early-onset scoliosis
      remains far from optimal and more development is on the way.

PMID- 24299697
TI  - Advanced course. Welcome address:.

PMID- 24299698
TI  - The Pediatric Posterior Fossa: an Embryologist's View.
AB  - The paediatric posterior fossa is a complex structure made up of both neural
      elements and skeletal pieces. The first structures to be formed are the neural
      elements followed later by bones moulded around the already patterned neural
      elements. The nervous structures derive from the neural tube at the exact level
      of the rhombencephalon (also called the hindbrain). This neural tube is segmented
      into neuromeres called the rhombomeres. These structures form compartments in
      which cell migration is restricted. Furthermore, these compartments display
      specific gene expression and if the expression of a gene is forced into an
      aberrant rhombomere, a severe defect is determined in its own development. The
      cerebellum, that is one of the major neural components at this level, derives
      from rhombomere 1. It grows in a rostral to caudal direction like a curtain
      because its rostral progression is prevented by the cerebellar tentorium. The
      cerebellum arises as two distinct primordia that unite on the midline thanks to
      migration of the primordium of this structure. An impairment of this structure
      will generate a defective fusion at the midline. It is important to note that the
      different anatomical parts of the cerebellum are not regulated by the same
      molecular processes leading to a heterogeneity of this organ. Lastly, the bony
      structures of the posterior fossa derive from the mesoderm. We will review the
      exact contribution of both the somites and the cephalic mesoderm in such a
      context. 

PMID- 24299699
TI  - The pediatric posterior fossa: fetal MRI.

PMID- 24299700
TI  - Rhombencephalic vascular malformations.

PMID- 24299701
TI  - The Vanishing Chiari II after in Utero Myelomeningocele Repair.

PMID- 24299702
TI  - The expanding joubert spectrum.

PMID- 24299703
TI  - Muscle and the cerebellum.

PMID- 24299704
TI  - Cerebellar involvement in the phakomatoses.

PMID- 24299705
TI  - The cerebellum in amino and organic acidurias.

PMID- 24299706
TI  - Posterior fossa tumors in children: differential diagnosis and advanced imaging
      techniques.

PMID- 24299707
TI  - Intra-abdominal hypertension and abdominal compartment syndrome:
      pathophysiological and non-operative management.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      conditions that commonly manifest in critically ill patients. They are associated
      with a multiplicity of pathophysiological disturbances. This study
      retrospectively reviewed literature relating to IAH and ACS published in the last
      two decades to consolidate an understanding of the epidemiology, etiology,
      pathophysiology, diagnosis and non-operative management of these conditions.
      Additionally, the authors of this study have recently conducted a large study on
      intra-abdominal pressures of consecutive catheterised patients admitted to the
      Intensive Care Unit (N.=403). A preliminary analysis of this study has also been
      included. 

PMID- 24299708
TI  - Colloids in surgery: bad drugs, bad protocol, or bad data analysis?

PMID- 24299709
TI  - Sedation after cardiac arrest and during therapeutic hypothermia.
AB  - Mild therapeutic hypothermia (MTH) has improved neurological outcome of comatose
      patients after cardiac arrest (CA). Since the first clinical studies performed in
      this setting, sedation has always been associated with cooling procedures. The
      use of sedative drugs during MTH is required because it allows faster achievement
      and better maintenance of target temperature. Further studies are necessary to
      prove any potential neuroprotective effects of sedation after CA. No differences
      in clinical outcomes have been found among different drugs, except for those
      related to their intrinsic pharmacological properties: the association
      propofol/remifentanil provides a faster recovery of consciousness than
      midazolam/fentanyl but is associated with the need of more vasopressors to
      maintain stable hemodynamic. Moreover, pharmacokinetic properties of these drugs
      are often altered during MTH so that standard drug regimens could result in
      overdosing because of reduced clearance. Neuromonitoring could be helpful to
      titrate drugs' effects and detect earlier complications (i.e. seizure), while a
      wake-up test should be avoided during the first 24 hours after CA. 

PMID- 24299710
TI  - Stop! Bang the drum slowly, proceed with caution when assessing obstructive sleep
      apnea.

PMID- 24299711
TI  - Genome chaos: survival strategy during crisis.
AB  - Genome chaos, a process of complex, rapid genome re-organization, results in the
      formation of chaotic genomes, which is followed by the potential to establish
      stable genomes. It was initially detected through cytogenetic analyses, and
      recently confirmed by whole-genome sequencing efforts which identified multiple
      subtypes including "chromothripsis", "chromoplexy", "chromoanasynthesis", and
      "chromoanagenesis". Although genome chaos occurs commonly in tumors, both the
      mechanism and detailed aspects of the process are unknown due to the inability of
      observing its evolution over time in clinical samples. Here, an experimental
      system to monitor the evolutionary process of genome chaos was developed to
      elucidate its mechanisms. Genome chaos occurs following exposure to
      chemotherapeutics with different mechanisms, which act collectively as stressors.
      Characterization of the karyotype and its dynamic changes prior to, during, and
      after induction of genome chaos demonstrates that chromosome fragmentation (C
      Frag) occurs just prior to chaotic genome formation. Chaotic genomes seem to form
      by random rejoining of chromosomal fragments, in part through non-homologous end
      joining (NHEJ). Stress induced genome chaos results in increased karyotypic
      heterogeneity. Such increased evolutionary potential is demonstrated by the
      identification of increased transcriptome dynamics associated with high levels of
      karyotypic variance. In contrast to impacting on a limited number of cancer
      genes, re-organized genomes lead to new system dynamics essential for cancer
      evolution. Genome chaos acts as a mechanism of rapid, adaptive, genome-based
      evolution that plays an essential role in promoting rapid macroevolution of new
      genome-defined systems during crisis, which may explain some unwanted
      consequences of cancer treatment. 

PMID- 24299713
TI  - Authors' Response to "Acupuncture for Chronic Back Pain: The Mysterious Case of
      the Excluded Data"

PMID- 24299712
TI  - Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and
      maintenance in obese men and women.
AB  - The present study investigated the impact of a Lactobacillus rhamnosus
      CGMCC1.3724 (LPR) supplementation on weight loss and maintenance in obese men and
      women over 24 weeks. In a double-blind, placebo-controlled, randomised trial,
      each subject consumed two capsules per d of either a placebo or a LPR formulation
      (1.6 * 10(8) colony-forming units of LPR/capsule with oligofructose and inulin).
      Each group was submitted to moderate energy restriction for the first 12 weeks
      followed by 12 weeks of weight maintenance. Body weight and composition were
      measured at baseline, at week 12 and at week 24. The intention-to-treat analysis
      showed that after the first 12 weeks and after 24 weeks, mean weight loss was not
      significantly different between the LPR and placebo groups when all the subjects
      were considered. However, a significant treatment * sex interaction was observed.
      The mean weight loss in women in the LPR group was significantly higher than that
      in women in the placebo group (P = 0.02) after the first 12 weeks, whereas it was
      similar in men in the two groups (P= 0.53). Women in the LPR group continued to
      lose body weight and fat mass during the weight-maintenance period, whereas
      opposite changes were observed in the placebo group. Changes in body weight and
      fat mass during the weight-maintenance period were similar in men in both the
      groups. LPR-induced weight loss in women was associated not only with significant
      reductions in fat mass and circulating leptin concentrations but also with the
      relative abundance of bacteria of the Lachnospiraceae family in faeces. The
      present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation
      helps obese women to achieve sustainable weight loss.

PMID- 24299714
TI  - Incidence and outcome of graft resorption in anterior lumbar interbody fusion:
      using femoral ring allografts and recombinant human bone morphogenetic protein-2.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine the incidence of
      resorption after anterior lumbar interbody fusion (ALIF) and its effect on
      outcome. SUMMARY OF BACKGROUND DATA: Recombinant human bone morphogenetic protein
      2 (rhBMP-2) used in ALIF has been associated with a 0.5% to 82% incidence of
      resorption. This has been described as either a complication or part of the
      natural history. We postulate that early resorption (<=4 mo) in ALIF using
      femoral ring allograft augmented with rhBMP-2 supplemented with posterior
      instrumentation has no effect on outcome. METHODS: Institutional review board
      approved retrospective 60 chart cohort study of ALIF using femoral ring allograft
      augmented rhBMP-2 supplemented with posterior instrumentation from May 5, 2005,
      to April 6, 2010. Two groups were based upon the presence or absence of early
      graft resorption (<=4 mo). Patients were seen prior to surgery and
      postoperatively until 29 +/- 20 months (last visit). Follow-up visual analogue
      scale pain scores and radiographical evidence of fusion were measured and
      compared between the 2 groups. RESULTS: Sixty patients, 27 females and 33 males
      had follow-up for 29 +/- 20 months. Group 1 (33 patients, 45 levels) and group 2
      (27 patients, 36 levels) were identical in age (P = 0.62), sex distribution (P =
      0.43), preoperative pain score (P = 0.63), and in the rhBMP-2 dose per level (P =
      0.77). There were no significant group differences in postoperative visual
      analogue scale scores but a trend to higher fusion rate in group 1 was seen (P =
      0.07) at 6 months. There was a 40% incidence of early resorption with no
      significant differences in visual analogue scale scores or fusion rate between
      both groups. CONCLUSION: There is a 40% incidence of early resorption (<=4 mo)
      that had no significant effect on pain score or fusion rate. Resorption should be
      considered part of the fusion process and not necessarily a complication. LEVEL
      OF EVIDENCE: 3.

PMID- 24299715
TI  - Survival and cost comparison of kyphoplasty and percutaneous vertebroplasty using
      German claims data.
AB  - STUDY DESIGN: Observational study. OBJECTIVE: Examine the overall survival and
      treatment costs from a third-party-payer perspective for patients with
      osteoporotic vertebral compression fractures (OVCFs) treated by vertebral
      augmentation or conservative treatment in Germany. SUMMARY OF BACKGROUND DATA:
      OVCFs are associated with increased morbidity, mortality and thus reduced quality
      of life. Vertebral augmentation has been shown to be effective in these
      fractures. The association between treatment and survivorship as well as cost per
      life year gained for balloon kyphoplasty (BKP) and percutaneous vertebroplasty
      (PVP) was analyzed in the Medicare population. Replication of these analyses is
      warranted for confidence in findings. METHODS: Claims data from a major health
      insurance fund were used. Mortality risk differences between operated (BKP, PVP)
      and nonoperated cohorts were assessed by Cox regression. Operated patient groups
      were established by propensity score matching adjusting for covariates. For the
      matched operated patients with OVCF, (2006-2010) survival was estimated by Kaplan
      Meier method. RESULTS: A total of 598 newly diagnosed patients with OVCF were
      operated of 3607 patients with OVCF. The operated cohort was 43% less likely to
      die than the nonoperated one in the 5-year study period (hazard ratio = 0.57; P <
      0.001). Patients who received BKP had higher 60-month adjusted survival rate
      (66.7%) than those who received PVP (58.7%) (P = 0.68). Cumulative 4-year mean
      overall costs after first diagnosis were lower for the BKP cohort (PVP: ?42,510
      vs. BKP: ?39,014). Initial upfront higher costs driven by surgical treatment for
      patients who received BKP are offset by considerable pharmacy costs in patients
      who received PVP. There were differences between the values of painkiller
      consumption (PVP: ?3321 vs. BKP: ?2224). CONCLUSION: Results suggest a higher
      overall survival rate for operated than nonoperated patients with OVCF and
      indicate a potential survival benefit for patients who received BKP compared with
      patients who received PVP. The reasons merit further investigation. Total costs
      were lower after 4 years for patients who received BKP versus PVP due to less
      consumption of pharmaceuticals. LEVEL OF EVIDENCE: 3.

PMID- 24299716
TI  - Low parathyroid hormone levels in patients who underwent/would undergo
      hemodialysis result in bone graft failure after posterolateral fusion.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To reveal the association between levels of
      parathyroid hormone (PTH) and outcome of bone fusion in patients who
      underwent/would undergo hemodialysis. SUMMARY OF BACKGROUND DATA: Among the
      different bone lesions observed in patients who underwent/would undergo
      hemodialysis, adynamic bone disease is regarded as a factor associated with bone
      graft failure because of severely reduced bone turnover. Although PTH levels
      reflect the pathological findings of bone lesions in patients who underwent/would
      undergo hemodialysis, the relationship between PTH levels and the outcome of bone
      fusion in patients who underwent/would undergo hemodialysis has not been
      investigated. METHODS: Patients who underwent/would undergo hemodialysis (n = 48)
      with lumbar spine lesion underwent posterolateral spinal fusion with
      instrumentation. The outcome of bone fusion was assessed radiographically 12
      months after surgery, and sensitivity and specificity were determined using
      preoperative PTH levels as the standard. RESULTS: A significant difference in PTH
      levels was observed between the good fusion (mean, 235.4 pg/mL) and poor fusion
      (mean, 100.0 pg/mL) groups. The intersection of the sensitivity and specificity
      plots, generated using preoperative PTH levels, was 150 pg/mL, and the area under
      the receiver operating characteristic curve was 0.72. CONCLUSION: Low PTH levels
      are a risk factor for bone graft failure in patients who underwent/would undergo
      hemodialysis. Accordingly, PTH level can be a useful predictor of the outcome of
      bone fusion. LEVEL OF EVIDENCE: 4.

PMID- 24299717
TI  - Cervical spine clearance protocols in level 1 trauma centers in the United
      States.
AB  - STUDY DESIGN: Observational, cross-sectional. OBJECTIVE: To evaluate cervical
      spine clearance protocols in level 1 trauma centers in the United States. SUMMARY
      OF BACKGROUND DATA: Cervical spine clearance protocols were developed to prevent
      missed injuries that could result in neurological deficits. The degree of
      incorporation of evidence-based guidelines into protocols at trauma centers in
      the United States is unknown. METHODS: Level 1 trauma (n = 191) centers in the
      United States were contacted. Each available protocol was reviewed for 4
      scenarios: clearing the asymptomatic patient, the imaging used in patients not
      amenable to clinical clearance, the management strategies for patients with
      persistent neck pain with a negative computed tomographic (CT) scan, and those
      who are obtunded. RESULTS: The response rate was 87%. Cervical spine clearance
      protocols existed in 57% of the institutions. National Emergency X-Radiography
      Utilization Study criteria to clear asymptomatic patients were recommended in 89%
      of protocols. Sixty percent of protocols used CT scans as the first line of
      imaging. In patients with persistent neck pain with negative CT scan flexion
      extension plain radiographs were the most common (30%) next step for clearance.
      In patients who are obtunded, a CT scan followed by a magnetic resonance imaging
      was the most common method (31%) of clearance. Eight percent of the protocols
      recommended dynamic flexion-extension views in patients who are obtunded, which
      are contraindicated. CONCLUSION: Written cervical spine clearance protocols exist
      in 57% of level 1 trauma centers in the United States. These protocols are highly
      variable and standardization and utilization of these protocols should be
      encouraged in all trauma centers to prevent missed injuries and neurological
      catastrophes. LEVEL OF EVIDENCE: 4.

PMID- 24299718
TI  - Rate of revision surgery after stand-alone lateral lumbar interbody fusion for
      lumbar spinal stenosis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To examine the reoperation
      rate, specifically the need for posterior decompression and/or fusion, in a
      cohort of patients who underwent stand-alone lateral lumbar interbody fusion for
      symptomatic spinal stenosis with instability or deformity. SUMMARY OF BACKGROUND
      DATA: Lateral lumbar interbody fusion provides a minimally invasive means of
      achieving interbody arthrodesis and indirect foraminal decompression while
      avoiding the potential morbidity of traditional anterior or posterior approaches.
      The revision rate for formal posterior decompression after isolated lateral
      lumbar interbody fusion for spinal stenosis is unknown. METHODS: One hundred
      seventeen patients who underwent stand-alone lateral lumbar interbody fusion for
      symptomatic spinal stenosis with an indication for fusion were included in the
      analysis. Detailed demographic and intraoperative data were collected. Clinical
      evaluation was done both preoperatively and at the final follow-up, and
      radiographical evaluation was done preoperatively and with the first
      postoperative standing radiographs. RESULTS: A total of 10.3% of patients who
      underwent stand-alone lateral lumbar interbody fusion ultimately required
      revision surgery, most commonly for persistent radiculopathy and symptomatic
      implant subsidence. Average time to revision was 10.8 months. There was no
      difference in radiographical correction between patients who did and did not
      require revision surgery. CONCLUSION: Lateral lumbar interbody fusion provides a
      minimally invasive means to treat lumbar spinal stenosis with an acceptable
      revision rate for formal posterior decompression at early follow-up. LEVEL OF
      EVIDENCE: 4.

PMID- 24299719
TI  - Cement leakage in percutaneous vertebroplasty for spinal metastases: a
      retrospective evaluation of incidence and risk factors.
AB  - STUDY DESIGN: Retrospective assessment of risk factors using univariate and
      multivariate analyses. OBJECTIVE: To evaluate risk factors retrospectively for
      cement leakage (CL), including vascular cement leakage (vCL) and cortical cement
      leakage (cCL), in percutaneous vertebroplasty of spinal metastasis. SUMMARY OF
      BACKGROUND DATA: Complications of vertebroplasty for spine metastasis are rare
      but related to extravertebral cement leakage that is pulmonary embolism and
      medullary compression. Better understanding of the risk factors for vascular and
      cortical types of cement leakage is necessary to prevent these complications.
      METHODS: Fifty-six cancer patients (30 females, 26 males; age, 56 +/- 12 yr) (81
      vertebrae) were treated in 58 sessions under fluoroscopy or computed tomography
      fluoroscopy guidance. Leakage rates were reported. The following items were
      assessed for occurrence of CL, vCL, and cCL: primary tumor site, prior
      radiotherapy or local tumor ablation or embolization, appearance on computed
      tomography, cortical osteolytic destruction, vertebral collapse, operator's
      experience, guidance modality, and cement filling. RESULTS: CL, vCL, and cCL
      rates were 53%, 25%, and 32%. History of prior treatment correlated with a
      decrease in CL (P = 0.018). vCL decreased when lung was the primary tumor site (P
      = 0.036), in osteolytic vertebrae (P = 0.033) or when there was a vertebral
      collapse (P = 0.037). cCL correlated with operator's experience (P = 0.021) and
      vertebral collapse (P < 0.001). Superior discal cCL correlated with superior
      endplate cortical destruction (P = 0.012). Although history of prior treatment
      seemed to be an independent protective factor (odds ratio = 0.24; 95% confidence
      interval, 0.087-0.7; P = 0.001), vertebral collapse was isolated as a risk factor
      for cCL (odds ratio = 32; 95% confidence interval, 6.7-161; P = 0.001).
      CONCLUSION: Risk factors for cCL and vCL are distinct. Vertebral collapse and
      cortical destruction are risk factors for cCL. History of prior treatment is a
      protective factor for CL. LEVEL OF EVIDENCE: 4.

PMID- 24299720
TI  - Prevertebral vascular and esophageal consideration during percutaneous cervical
      disc procedures.
AB  - STUDY DESIGN: A retrospective review series. OBJECTIVE: To identify vascular
      anatomy and esophageal deviations that may interfere with a percutaneous anterior
      approach in cervical spine surgery. SUMMARY OF BACKGROUND DATA: The percutaneous
      anterior approach has been used for minimally invasive interventions of cervical
      disc diseases. Although the percutaneous anterior approach is frequently
      performed, reports of obstructing anatomical structures and procedural risks are
      limited. METHODS: Cervical magnetic resonance images obtained from December 2012
      to April 2013 from a total of 511 patients at Guro Teun Teun Hospital were
      evaluated in this study. Each axial T2-weighted MR image from the disc levels of
      C3-C4 to C6-C7 (total, 3066 images) was reviewed to check for the presence of
      small vessels along the trajectories of percutaneous cervical procedures on the
      left and right sides. Esophageal deviation was also measured at level C6-C7.
      RESULTS: Small vessels in the anterior neck were present, respectively, in 50.5%
      (trajectory on the left side) and in 49.1% (trajectory on the right side) at disc
      level C3-C4, in 30.3% and 28.8% at C4-C5, in 24.1% and 7.6% at C5-C6, and in
      55.2% and 43.1% at C6-C7. There were no differences in the number of small
      vessels between the left and right sides at the upper cervical level (C3-C4-C5),
      but small vessels were less frequently observed on the right side at lower
      cervical levels (C5-C6-C7). Differences in esophageal deviation were also
      observed, with less deviation to the right side (0.63 +/- 0.35 cm) than the left
      (1.18 +/- 0.52 cm). As well, an esophageal diverticulum was observed in 1 case on
      the left side. CONCLUSION: Although surgical approaches are mostly concerned with
      the location of pathology to be removed, a right-sided percutaneous approach
      seems preferable because poses less of a risk of encountering small vessels and
      causing esophageal injury. LEVEL OF EVIDENCE: 4.

PMID- 24299721
TI  - A prospective comparative study of 2 minimally invasive decompression procedures
      for lumbar spinal canal stenosis: unilateral laminotomy for bilateral
      decompression (ULBD) versus muscle-preserving interlaminar decompression (MILD).
AB  - STUDY DESIGN: A prospective comparative study. OBJECTIVE: To compare
      prospectively 2 different types of minimally invasive surgery for lumbar spinal
      canal stenosis (LSCS): unilateral laminotomy for bilateral decompression (ULBD),
      and muscle-preserving interlaminar decompression (MILD). SUMMARY OF BACKGROUND
      DATA: Although previous studies have reported several procedures of minimally
      invasive surgery for the treatment of LSCS, no articles prospectively compared 2
      different procedures. METHODS: From 2005 to 2009, we prospectively enrolled 50
      patients with LSCS for the treatment with ULBD, and 50 patients for MILD. The
      patients' symptoms were evaluated using Japanese Orthopedic Association (JOA)
      score, JOA Back Pain Evaluation Questionnaire, and visual analogue scale before
      and 2 years after operation. For radiological evaluation, changes in disc height,
      sagittal translation, and lateral wedging at the decompressed segment, as well as
      lumbar lordosis were investigated using plain radiographs. RESULTS: Ninety-nine
      of 100 patients were followed for a minimum of 2 years. No significant
      differences were found in the recovery rate of JOA score, improvement of JOA Back
      Pain Evaluation Questionnaire, and changes of the visual analogue scale between
      the 2 groups. Radiologically, no significant differences were present in the
      postoperative degenerative changes in disc height, sagittal translation, and
      lateral wedging. In multilevel surgical procedures; however, clinical scores in
      low back pain, and lumbar function were significantly greater in the ULBD group
      than those in the MILD group. The lateral wedging change at L2-L3 and L3-L4 more
      frequently occurred in the ULBD group than in the MILD group. On the contrary,
      the number of patients who demonstrated the postoperative sagittal translation at
      L4-L5 was significantly greater in the MILD group than in the ULBD group.
      CONCLUSION: Both MILD and ULBD were efficacious procedures for improving
      neurological symptoms in patients with LSCS. In multilevel decompression surgical
      procedures, ULBD was superior to MILD in terms of improvement of low back pain
      and lumbar function at the 2-year time point. LEVEL OF EVIDENCE: 3.

PMID- 24299722
TI  - Association between urine cotinine levels and bone mineral density in lumbar
      spine and femoral neck among adult males.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate an association
      between tobacco exposure as determined by urine cotinine and bone mineral density
      (BMD) in femoral neck and lumbar spine. SUMMARY OF BACKGROUND DATA: Loss of BMD
      is 1 of the major causes of spine and femoral neck fractures in the elderly
      population. There is limited literature on risk factors to loss of BMD, in
      particular, among males. METHODS: We analyzed data of 770 males older than 30
      years, which were collected from the cross-sectional Fifth Korea National Health
      and Nutrition Examination Survey, with t tests, analysis of variance, and
      multiple linear regressions. RESULTS: The means of femoral neck BMD (T score)
      significantly decreased with increasing age, -0.08, -0.63, and -1.49 in males
      aged 30 to 40 years, 50 to 69 years, and 70 to 95 years, respectively (P <
      0.001). The same trend was observed in lumbar spine BMD. Although education (P <
      0.001) and income (P = 0.021) were associated with femoral neck T score, only
      education (P = 0.034) was associated with lumbar spine T score. The group who had
      urine cotinine level of more than 10 MUg/mL (active smokers or nonsmokers who
      were exposed to second-hand smoking) had lower femoral neck T score (-0.43 +/-
      0.98) than the group who had cotinine level of 10 MUg/mL or less (-0.33 +/- 0.89)
      (P = 0.114). In the multiple linear regressions, age, urine cotinine level, and
      body mass index were statistically related to femoral neck and lumbar spine T
      score. CONCLUSION: Our findings suggest that tobacco exposure by active or
      passive smoking and lower body mass index seem to exert a negative effect on
      femoral neck and lumbar spine BMD. LEVEL OF EVIDENCE: N/A.

PMID- 24299723
TI  - Risk factors for postoperative retropharyngeal hematoma after anterior cervical
      spine surgery.
AB  - STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: To
      investigate risk factors involved in the development of anterior cervical
      hematomas and determine any impact on patient outcomes. SUMMARY OF BACKGROUND
      DATA: Postoperative (PO) hematomas after anterior cervical spine surgery require
      urgent recognition and treatment to avoid catastrophic patient morbidity or
      death. Current studies of PO hematomas are limited. METHODS: Cervical spine
      surgical procedures performed on adults by the senior author at a single academic
      institution from 1995 to 2012 were evaluated. Demographic data, surgical history,
      operative data, complications, and neck disability index (NDI) scores were
      recorded prospectively. Cases complicated by PO hematoma were reviewed, and time
      until hematoma development and surgical evacuation were determined. Patients who
      developed a hematoma (HT group) were compared with those that did not (no-HT
      group) to identify risk factors. NDI outcomes were compared at early (<11 mo) and
      late (>11 mo) time points. RESULTS: There were 2375 anterior cervical spine
      surgical procedures performed with 17 occurrences (0.7%) of PO hematoma. In 11
      patients (65%) the hematoma occurred within 24 hours PO, whereas 6 patients (35%)
      presented at an average of 6 days postoperatively. All underwent hematoma
      evacuation, with 2 patients (12%) requiring emergent cricothyroidotomy. Risk
      factors for hematoma were found to be (1) the presence of diffuse idiopathic
      skeletal hyperostosis (relative risk = 13.2, 95% confidence interval = 3.2-54.4),
      (2) presence of ossification of the posterior longitudinal ligament (relative
      risk = 6.8, 95% confidence interval = 2.3-20.6), (3) therapeutic heparin use
      (relative risk 148.8, 95% confidence interval = 91.3-242.5), (4) longer operative
      time, and (5) greater number of surgical levels. The occurrence of a PO hematoma
      was not found to have a significant impact on either early (HT: 30, no-HT: 28; P
      = 0.86) or late average NDI scores (HT: 28, no-HT 31; P = 0.76). CONCLUSION: With
      fast recognition and treatment, no long-term detriment from PO anterior cervical
      hematoma was found. We identified risk factors to be (1) presence of diffuse
      idiopathic skeletal hyperostosis, (2) presence of ossification of the posterior
      longitudinal ligament, (3) therapeutic heparin use, (4) longer operative time,
      and (5) greater number of surgical levels. LEVEL OF EVIDENCE: 4.

PMID- 24299724
TI  - Repeat spine imaging in transferred emergency department patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: Assess frequency of repeat spine
      imaging in patients transferred with known spine injuries from outside hospital
      (OSH) to tertiary receiving institution (RI). SUMMARY OF BACKGROUND DATA:
      Unnecessary repeat imaging after transfer has started to become a recognized
      problem with the obvious issues related to repeat imaging along with potential
      for iatrogenic injury with movement of patients with spine problems. METHODS:
      Consecutive adult patients presenting to a single 1-level trauma center with
      spine injuries during a 51-month period were reviewed (n = 4500), resulting in
      1427 patients transferred from OSH emergency department. All imaging and
      radiology reports from the OSH were reviewed, as well as studies performed at RI.
      A repeat was the same imaging modality used on the same spine region as OSH
      imaging. RESULTS: The overall rate of repeat spine imaging for both OSH imaging
      sent and not sent was 23%, and 6% if repeat spine imaging via traumagram
      (partial/full-body computed tomography [CT]) was excluded as a repeat. The
      overall rate of repeat CT was 29% (7% dedicated spine CT scans and 22% part of
      nondedicated spine CT scan).An observation of only those patients with OSH
      imaging that was sent and viewable revealed that 23% underwent repeat spine
      imaging with 23% undergoing repeat spine CT and 41% repeat magnetic resonance
      imaging.In those patients with sent and viewable OSH imaging, a lack of
      reconstructions prompted 14% of repeats, whereas inadequate visualization of
      injury site prompted 8%. In only 8% of the repeats did it change management or
      provide necessary surgical information. CONCLUSION: This study is the first to
      investigate the frequency of repeat spine imaging in transfers with known spine
      injuries and found a substantially high rate of repeat spine CT with minimal
      alteration in care. Potential solutions include only performing scans at the OSH
      necessary to establish a diagnosis requiring transfer and improving communication
      between OSH and RI physicians. LEVEL OF EVIDENCE: 4.

PMID- 24299725
TI  - The safety and accuracy of freehand pedicle screw placement in the subaxial
      cervical spine: a series of 45 consecutive patients.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess the safety and
      accuracy of subaxial cervical pedicle screw placement with freehand technique and
      to report the technical nuances. SUMMARY OF BACKGROUND DATA: Although the
      efficacy and safety of freehand screw fixation in thoracic and lumbar vertebrae
      is proven, reports on this technique of screw insertion in the subaxial cervical
      spine are lacking. METHODS: From March 2012 to September 2013, 45 consecutive
      patients underwent posterior cervical fusion. The diagnoses were trauma (22
      patients), degenerative disease (18 patients), discitis/osteomyelitis (2
      patients), pathological fracture (2 patients), and postlaminoplasty kyphosis (1
      patient). Preoperative computed tomography (CT) was performed in all patients. We
      included patients whose outer diameter of the pedicle was greater than 3.0 mm.
      The standard entry points were modified according to the CT anatomy of each
      patient. A small pilot hole was fashioned at a predetermined entry point. Then, a
      2.5-mm diameter curved pedicle probe was slowly inserted with a medial trajectory
      into the pedicle. After ball-tip probing and tapping, the screw was inserted. If
      ball-tip probing was suggestive of risk to neurovascular structures, conversion
      to a lateral mass screw was performed. Postoperatively, a CT scan was performed
      in all patients and the conversion rate from pedicle to lateral mass screw was
      recorded. The breech rate of pedicle screws was also analyzed. RESULTS: There
      were 256 planned pedicle screws and 20 incidences (7.8%) of conversion to lateral
      mass screws. Lateral wall violation was observed in 14 pedicle screws (accuracy
      rate: 94.1%) on the postoperative CT scan. No medial, superior, and inferior
      pedicle wall violations were observed. There was no patient who developed
      symptoms related to vertebral artery stenosis. CONCLUSION: Adherence to the
      surgical tips presented in this article may lead to safe and effective freehand
      placement of cervical pedicle screws. LEVEL OF EVIDENCE: 3.

PMID- 24299726
TI  - The role of sacrolumbar fat grafting in the treatment of spinal fusion
      instrumentation-related chronic low back pain: a preliminary report.
AB  - STUDY DESIGN: A report of 2 cases. OBJECTIVE: The purpose of this article is to
      report 2 preliminary cases with instrumentation-related chronic low back pain
      (CLBP) successfully treated with fat graft in the sacrolumbar region. SUMMARY OF
      BACKGROUND DATA: Patients undergoing successful spinal fusion surgery may
      experience new or recurrent CLBP. Instrumentation-related soft-tissue irritation
      is a well-known etiology of this frustrating condition. Treatment options vary
      from conservative treatment till instrumentation removal, with no consensus on
      their efficacy. METHODS: A 32-year-old patient and a 37-year-old patient with
      instrumentation-related debilitating CLBP visual analogue scale score 7 and 10,
      respectively, underwent 1 session of fat grafting in the sacrolumbar region.
      RESULTS: At 9-month and 6-month follow-ups, both patients reported a substantial
      pain relief, a considerable improvement in daily quality of life and satisfaction
      for less implant palpability and visibility. CONCLUSION: The encouraging results
      of these preliminary cases may open new horizons for a multidisciplinary approach
      in treating instrumentation-related CLBP. Fat grafting may represent a valid and
      minimal invasive option to be taken into account when established therapeutic
      options fail. Further experience with longer follow-up is needed to confirm our
      findings. LEVEL OF EVIDENCE: 5.

PMID- 24299727
TI  - Multicenter prospective nonrandomized controlled clinical trial to prove
      neurotherapeutic effects of granulocyte colony-stimulating factor for acute
      spinal cord injury: analyses of follow-up cases after at least 1 year.
AB  - STUDY DESIGN: An open-labeled multicenter prospective nonrandomized controlled
      clinical trial. OBJECTIVE: To confirm the feasibility of using granulocyte colony
      stimulating factor (G-CSF) for treatment of acute spinal cord injury (SCI).
      SUMMARY OF BACKGROUND DATA: We previously reported that G-CSF promotes functional
      recovery after compression-induced SCI in mice. On the basis of these findings,
      we conducted a multicenter prospective controlled clinical trial to assess the
      feasibility of G-CSF therapy for patients with acute SCI. METHODS: The trial ran
      from August 2009 to March 2011, and included 41 patients with SCI treated within
      48 hours of onset. Informed consent was obtained from all patients. After
      providing consent, patients were divided into 2 groups. In the G-CSF group (17
      patients), G-CSF (10 MUg/kg/d) was intravenously administered for 5 consecutive
      days, and in the control group (24 patients), patients were similarly treated
      except for the G-CSF administration. We evaluated motor and sensory functions
      using the American Spinal Cord Injury Association score and American Spinal Cord
      Injury Association impairment scale at 1 week, 3 months, 6 months, and 1 year
      after onset. RESULTS: Only 2 patients did not experience American Spinal Cord
      Injury Association impairment scale improvement in the G-CSF group. In contrast,
      15 patients in the control group did not experience American Spinal Cord Injury
      Association impairment scale improvement. In the analysis of increased American
      Spinal Cord Injury Association motor score, a significant increase in G-CSF group
      was detected from 1 week after the administration compared with the control
      group. After that, some spontaneous increase of motor score was detected in
      control group, but the significant increase in G-CSF group was maintained until 1
      year of follow-up. CONCLUSION: Despite the limitation that patient selection was
      not randomized, the present results suggest the possibility that G-CSF
      administration has beneficial effects on neurological recovery in patients with
      acute SCI. LEVEL OF EVIDENCE: 3.

PMID- 24299728
TI  - Corneal viscoelastic differences between pseudoexfoliative glaucoma and primary
      open-angle glaucoma.
AB  - PURPOSE: The aims of this study were to assess the biomechanical properties of
      corneas with pseudoexfoliative glaucoma (PEXG) and to compare them with those of
      patients with primary open-angle glaucoma (POAG). METHODS: This prospective,
      comparative case series consisted of 73 eyes of 73 patients, 35 eyes with PEXG
      (PEXG group) and 38 eyes with POAG (POAG group). Corneal hysteresis (CH), corneal
      resistance factor (CRF), corneal-compensated intraocular pressure (IOPCC), and
      Goldmann-correlated intraocular pressure (IOPG) were determined by using ocular
      response analyzer (ORA). IOP using Goldmann applanation tonometer (GAT) and
      ultrasonic central corneal thickness (CCT) were also measured for each eye.
      Exclusion criteria included refractive error/astigmatism of >3.00 D, history of
      intraocular surgery, corneal disease, angle-closure glaucoma, and secondary
      glaucoma other than PEXG. In cases where both eyes were eligible, the right eye
      was preferred for analysis. The main outcome measures were CH, CRF, IOPCC, IOPG,
      and GAT. The results were statistically analyzed by using t test, general linear
      model, and the Pearson correlation test. RESULTS: The mean CH was found to be
      significantly lower in patients with PEXG (8.8 +/- 1.4 mm Hg) than those with
      primary open-angle glaucoma (9.9 +/- 1.2 mm Hg; P=0.0007). The mean CRF was found
      to be significantly lower in patients with PEXG (9.5 +/- 1.8 mm Hg) than those
      with POAG (11.1 +/- 1.3 mm Hg; P<0.0001). IOPCC was not significantly different
      between the groups (PEXG, 16.7 +/- 2.5 mm Hg; POAG, 16.9 +/- 2.4 mm Hg; P=0.72).
      IOPG was significantly lower in PEXG group (14.7 +/- 2.7 mm Hg) compared with the
      POAG group (16.5 +/- 2.5 mm Hg; P=0.004). GAT was significantly lower in the PEXG
      group (14.6 +/- 2.7 mm Hg) compared with the POAG group (16.4 +/- 2.8 mm Hg;
      P=0.007). There was no significant difference between the groups regarding mean
      CCT (PEXG, 546.1 +/- 34.9 MU; POAG, 549.1 +/- 25 MU; P=0.66) and mean age (PEXG,
      70.3 +/- 8.2; POAG, 67.6 +/- 8.8; P=0.17). The difference between the IOPCC and
      the GAT was 2.1 and 0.5 mm Hg in both PEXG and POAG groups, respectively.
      CONCLUSIONS: Patients with PEXG had lower CH and CRF values than those with POAG.
      These findings require further investigation to assess the role of differing
      corneal biomechanical properties between the 2 groups and its association with
      poor prognosis among patients with PEXG.

PMID- 24299729
TI  - Autologous tragal perichondrium patch graft for ahmed glaucoma valve tube
      exposure.
AB  - PURPOSE: To describe a novel method of repair for an exposed Ahmed valve tube
      using tragal perichondrium. METHODS: A 56-year-old man with a severe chemical
      burn was referred to our clinic for the management of total limbal stem cell
      deficiency. During the treatment, an Ahmed valve tube was implanted to control
      refractory glaucoma. Tube exposure occurred 39 months after implantation. A
      glycerin-preserved donor sclera patch graft was used to cover the exposed lesion.
      However, 21 months later, the tube became exposed again. Autologous tragal
      perichondrium was then harvested and used to repair the exposed tube. RESULTS:
      The exposed tube was closed successfully without recurrence, graft thinning, or
      graft-related infection or inflammation over a 20-month follow-up period.
      CONCLUSIONS: Perichondrial patch grafts can be a useful alternative for repair of
      exposed glaucoma drainage tubes.

PMID- 24299730
TI  - Parapapillary gamma zone hole.
AB  - PURPOSE: To describe the appearance of a defect in the parapapillary region of a
      highly myopic eye. METHODS: During a routine ophthalmologic examination, in a 26
      year-old man with a visual acuity of 0.80 and a refractive error of -10.25 D, a
      dehiscence in the parapapillary region was detected. A choroidal vessel appeared
      to emerge out of the dehiscence RESULTS: : Optical coherence tomography (OCT)
      revealed an apparent hole in the underlying scleral wall opening into a
      retrobulbar empty space. The latter was delimited by the dura mater as shown by a
      vertical bright band. Inside of the dura mater, the retrobulbar orbital
      cerebrospinal fluid space was widened. Interestingly, the same eye showed a
      parapapillary intrachoroidal cavitation almost completely hiding the main
      temporal inferior vessel branch. In addition, the optic disc was vertically
      rotated and slightly obliquely tilted so that its en face appearance was smaller
      than its surface as it appeared on the OCT image. CONCLUSIONS: The OCT revealed a
      parapapillary gamma zone hole in a highly myopic eye in association with a
      vertically rotated and slightly tilted optic disc with an inferior parapapillary
      intrachoroidal cavitation. The illustration may show the usefulness of the
      differentiation between the beta zone, gamma zone, and delta zone in the
      parapapillary region.

PMID- 24299731
TI  - Vaccine quality and safety: scrutinizing the reported 3-fold increase in adverse
      effects following immunization (Aefi) in India.
AB  - BACKGROUND: There has been major controversy over vaccine safety in India
      following newspaper reports citing right to information (RTI) disclosure that
      there have been increasing vaccine related deaths following immunization in
      children in the recent years. METHODS: Secondary data analysis. RESULTS AND
      CONCLUSION: Adverse effect following immunization (AEFI) events in recent years
      are being linked to closure of three government owned vaccine producing public
      sector units (PSU) closures in India. The media reports quoting government
      sources suggest that the total number of reported deaths due to AEFI in a pre
      closure of vaccine PSUs 7 years (2001-2007) was 136, whereas it is 355 in the
      post vaccine PSU closure 3 years (2008 to 2010). There is an issue of
      comparability of numbers of AEFI deaths pre- (2001-2007) and post-vaccine PSU
      closure era (2008-2011) and linking increased AEFI deaths to vaccine PSU closure.

PMID- 24299732
TI  - Self-reporting scaffolds for 3-dimensional cell culture.
AB  - Culturing cells in 3D on appropriate scaffolds is thought to better mimic the in
      vivo microenvironment and increase cell-cell interactions. The resulting 3D
      cellular construct can often be more relevant to studying the molecular events
      and cell-cell interactions than similar experiments studied in 2D. To create
      effective 3D cultures with high cell viability throughout the scaffold the
      culture conditions such as oxygen and pH need to be carefully controlled as
      gradients in analyte concentration can exist throughout the 3D construct. Here we
      describe the methods of preparing biocompatible pH responsive sol-gel nanosensors
      and their incorporation into poly(lactic-co-glycolic acid) (PLGA) electrospun
      scaffolds along with their subsequent preparation for the culture of mammalian
      cells. The pH responsive scaffolds can be used as tools to determine
      microenvironmental pH within a 3D cellular construct. Furthermore, we detail the
      delivery of pH responsive nanosensors to the intracellular environment of
      mammalian cells whose growth was supported by electrospun PLGA scaffolds. The
      cytoplasmic location of the pH responsive nanosensors can be utilized to monitor
      intracellular pH (pHi) during ongoing experimentation. 

PMID- 24299733
TI  - It's not you, it's me: time to narrow the gap in weekend care.

PMID- 24299734
TI  - Integrating patient safety into health professionals' curricula: a qualitative
      study of medical, nursing and pharmacy faculty perspectives.
AB  - BACKGROUND: As efforts to integrate patient safety into health professional
      curricula increase, there is growing recognition that the rate of curricular
      change is very slow, and there is a shortage of research that addresses critical
      perspectives of faculty who are on the 'front-lines' of curricular innovation.
      This study reports on medical, nursing and pharmacy teaching faculty perspectives
      about factors that influence curricular integration and the preparation of safe
      practitioners. METHODS: Qualitative methods were used to collect data from 20
      faculty members (n=6 medical from three universities; n=6 pharmacy from two
      universities; n=8 nursing from four universities) engaged in medical, nursing and
      pharmacy education. Thematic analysis generated a comprehensive account of
      faculty perspectives. RESULTS: Faculty perspectives on key challenges to safe
      practice vary across the three disciplines, and these different perspectives lead
      to different priorities for curricular innovation. Additionally, accreditation
      and regulatory requirements are driving curricular change in medicine and
      pharmacy. Key challenges exist for health professional students in clinical
      teaching environments where the culture of patient safety may thwart the
      preparation of safe practitioners. CONCLUSIONS: Patient safety curricular
      innovation depends on the interests of individual faculty members and the
      leveraging of accreditation and regulatory requirements. Building on existing
      curricular frameworks, opportunities now need to be created for faculty members
      to act as champions of curricular change, and patient safety educational
      opportunities need to be harmonises across all health professional training
      programmes. Faculty champions and practice setting leaders can collaborate to
      improve the culture of patient safety in clinical teaching and learning settings.

PMID- 24299735
TI  - Genome-wide nucleosome map and cytosine methylation levels of an ancient human
      genome.
AB  - Epigenetic information is available from contemporary organisms, but is difficult
      to track back in evolutionary time. Here, we show that genome-wide epigenetic
      information can be gathered directly from next-generation sequence reads of DNA
      isolated from ancient remains. Using the genome sequence data generated from hair
      shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate
      the first ancient nucleosome map coupled with a genome-wide survey of cytosine
      methylation levels. The validity of both nucleosome map and methylation levels
      were confirmed by the recovery of the expected signals at promoter regions,
      exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed
      distinct DNA positioning biases, attesting to nucleotide-level accuracy. The
      ancient methylation levels exhibited high conservation over time, clustering
      closely with modern hair tissues. Using ancient methylation information, we
      estimated the age at death of the Saqqaq individual and illustrate how epigenetic
      information can be used to infer ancient gene expression. Similar epigenetic
      signatures were found in other fossil material, such as 110,000- to 130,000-yr
      old bones, supporting the contention that ancient epigenomic information can be
      reconstructed from a deep past. Our findings lay the foundation for extracting
      epigenomic information from ancient samples, allowing shifts in epialleles to be
      tracked through evolutionary time, as well as providing an original window into
      modern epigenomics. 

PMID- 24299736
TI  - From single-cell to cell-pool transcriptomes: stochasticity in gene expression
      and RNA splicing.
AB  - Single-cell RNA-seq mammalian transcriptome studies are at an early stage in
      uncovering cell-to-cell variation in gene expression, transcript processing and
      editing, and regulatory module activity. Despite great progress recently,
      substantial challenges remain, including discriminating biological variation from
      technical noise. Here we apply the SMART-seq single-cell RNA-seq protocol to
      study the reference lymphoblastoid cell line GM12878. By using spike-in
      quantification standards, we estimate the absolute number of RNA molecules per
      cell for each gene and find significant variation in total mRNA content: between
      50,000 and 300,000 transcripts per cell. We directly measure technical
      stochasticity by a pool/split design and find that there are significant
      differences in expression between individual cells, over and above technical
      variation. Specific gene coexpression modules were preferentially expressed in
      subsets of individual cells, including one enriched for mRNA processing and
      splicing factors. We assess cell-to-cell variation in alternative splicing and
      allelic bias and report evidence of significant differences in splice site usage
      that exceed splice variation in the pool/split comparison. Finally, we show that
      transcriptomes from small pools of 30-100 cells approach the information content
      and reproducibility of contemporary RNA-seq from large amounts of input material.
      Together, our results define an experimental and computational path forward for
      analyzing gene expression in rare cell types and cell states. 

PMID- 24299737
TI  - Zinc finger nuclease-mediated knockout of AHR or ARNT in human breast cancer
      cells abolishes basal and ligand-dependent regulation of CYP1B1 and
      differentially affects estrogen receptor alpha transactivation.
AB  - In this study, we used zinc finger nuclease-mediated knockout of the aryl
      hydrocarbon receptor (AHR) or AHR nuclear translocator (ARNT) in MCF7 and AHR
      knockout in MDA-MB-231 human breast cancer cells to investigate cross talk among
      AHR, ARNT, and estrogen receptor alpha (ERalpha). Knockout of AHR or ARNT
      prevented the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-dependent induction of
      all AHR target genes examined. Knockout of AHR or ARNT also significantly reduced
      basal cytochrome P4501B1 (CYP1B1) expression levels, which were restored with
      overexpression of either protein but not with a DNA binding-deficient AHR mutant.
      Basal and TCDD-, 17beta-estradiol (E2)-, or TCDD + E2-dependent recruitment of
      AHR, ARNT, ERalpha, NCoA3, and RNA polymerase II to CYP1B1 as well as CYP1B1 mRNA
      levels were abolished in MCF7-AHR((ko)) and MDA-MB-231 AHR(ko) cells. However,
      reduced but significant E2-dependent recruitment of ERalpha, NCoA3, and RNA
      polymerase II to CYP1B1 and weak increases in CYP1B1 mRNA levels were observed in
      MCF7 ARNT((ko)) cells. Interestingly, E2-dependent increases in trefoil factor 1,
      but not growth regulation by estrogen in breast cancer 1 (GREB1) mRNA levels,
      were dependent on ARNT expression. Moreover, the TCDD-dependent increases in the
      proteolytic degradation of ERalpha were prevented by the loss of AHR or ARNT. Our
      data show that AHR and ARNT play critical roles in the basal, TCDD, and E2
      induced regulation of CYP1B1 but also reveal distinct roles for both proteins in
      ERalpha transactivation.

PMID- 24299738
TI  - Glial cell response to 3,4-(+/-)-methylenedioxymethamphetamine and its
      metabolites.
AB  - 3,4-(+/-)-Methylenedioxymethamphetamine (MDMA) and 3,4-(+/-)
      methylenedioxyamphetamine (MDA), a primary metabolite of MDMA, are
      phenylethylamine derivatives that cause serotonergic neurotoxicity. Although
      several phenylethylamine derivatives activate microglia, little is known about
      the effects of MDMA on glial cells, and evidence of MDMA-induced microglial
      activation remains ambiguous. We initially determined microglial occupancy status
      of the parietal cortex in rats at various time points following a single
      neurotoxic dose of MDMA (20mg/kg, SC). A biphasic microglial response to MDMA was
      observed, with peak microglial occupancy occurring 12- and 72-h post-MDMA
      administration. Because direct injection of MDMA into the brain does not produce
      neurotoxicity, the glial response to MDMA metabolites was subsequently examined
      in vivo and in vitro. Rats were treated with MDA (20mg/kg, SC) followed by ex
      vivo biopsy culture to determine the activation of quiescent microglia. A
      reactive microglial response was observed 72 h after MDA administration that
      subsided by 7 days. In contrast, intracerebroventricular (ICV) administration of
      MDA failed to produce a microglial response. However, thioether metabolites of
      MDA derived from alpha-methyldopamine (alpha-MeDA) elicited a robust microglial
      response following icv injection. We subsequently determined the direct effects
      of various MDMA metabolites on primary cultures of E18 hippocampal mixed glial
      and neuronal cells. 5-(Glutathion-S-yl)-alpha-MeDA, 2,5-bis-(glutathion-S-yl)
      alpha-MeDA, and 5-(N-acetylcystein-S-yl)-alpha-MeDA all stimulated the
      proliferation of glial fibrillary acidic protein-positive astrocytes at a dose of
      10 uM. The findings indicate that glial cells are activated in response to
      MDMA/MDA and support a role for thioether metabolites of alpha-MeDA in the
      neurotoxicity.

PMID- 24299741
TI  - Glucocorticoids and foetal heart maturation; implications for prematurity and
      foetal programming.
AB  - Glucocorticoids are steroid hormones, essential in mammals to prepare for life
      after birth. Blood levels of glucocorticoids (cortisol in most mammals including
      humans; corticosterone in rats and mice) rise dramatically shortly before birth.
      This is mimicked clinically in the routine administration of synthetic
      glucocorticoids to pregnant women threatened by a preterm birth or to preterm
      infants to improve neonatal survival. Whilst effects on lung are well documented
      and essential for postnatal survival, those on heart are less well known. In this
      study, we review recent evidence for a crucial role of glucocorticoids in late
      gestational heart maturation. Either insufficient or excessive glucocorticoid
      exposure before birth may alter the normal glucocorticoid-regulated trajectory of
      heart maturation with potential life-long consequences. 

PMID- 24299739
TI  - Stem cells for skeletal muscle regeneration: therapeutic potential and
      roadblocks.
AB  - Conditions involving muscle wasting, such as muscular dystrophies, cachexia, and
      sarcopenia, would benefit from approaches that promote skeletal muscle
      regeneration. Stem cells are particularly attractive because they are able to
      differentiate into specialized cell types while retaining the ability to self
      renew and, thus, provide a long-term response. This review will discuss recent
      advancements on different types of stem cells that have been attributed to be
      endowed with muscle regenerative potential. We will discuss the nature of these
      cells and their advantages and disadvantages in regards to therapy for muscular
      dystrophies. 

PMID- 24299740
TI  - Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during
      lactation in rats.
AB  - The contribution of hypothalamic appetite-regulating peptides to further
      hyperphagia accompanying the course of lactation in rats was investigated by
      using PCR array and real-time PCR. Furthermore, changes in the mRNA expression
      for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were
      analyzed at all stages of pregnancy and lactation, and also after weaning. Food
      intake was significantly higher during pregnancy, lactation, and after weaning
      than during non-lactation periods. During lactation, ARC expression of mRNAs for
      agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs
      for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in
      comparison with non-lactation periods. The increase in AgRP mRNA expression
      during lactation was especially marked. The plasma level of leptin was
      significantly decreased during the course of lactation, whereas that of acyl
      ghrelin was unchanged. In addition, food intake was negatively correlated with
      the plasma leptin level during lactation. This study has clarified synchronous
      changes in the expression of many appetite-regulating peptides in ARC of rats
      during lactation. Our results suggest that hyperphagia during lactation in rats
      is caused by decreases in POMC and CCK expression and increases in AgRP
      expression in ARC, the latter being most notable. Together with the decrease in
      the blood leptin level, such changes in mRNA expression may explain the further
      hyperphagia accompanying the course of lactation. 

PMID- 24299742
TI  - Ultradrawing novel ultra-high molecular weight polyethylene fibers filled with
      bacterial cellulose nanofibers.
AB  - Novel ultrahigh molecular weight polyethylene (UHMWPE)/bacterial cellulose (BC)
      (F100BCy) and UHMWPE/modified bacterial cellulose (MBC) (F100MBCx-y) as-prepared
      fibers were prepared and ultra-drawn. The achievable draw ratio (Dra) values of
      each F100MBCx-y as-prepared fiber series specimens approached a maximum value as
      their MBC contents reached the optimal value at 0.0625phr. In which, the maximum
      Dra value obtained for F100MBCx-0.0625 as-prepared fiber specimen prepared at the
      optimal MBC content reached another maximum value at 347 as the weight ratio of
      maleic anhydride grafted polyethylene to BC approach an optimal value at 10. In
      contrast, no significant improvement in Dra values was found for F100BCy as
      prepared fiber specimens. To understand these interesting ultradrawing properties
      described above, Fourier transform infra-red, specific surface areas, and
      transmission electron microcopic analyses of original and modified BC nanofibers
      together with the thermal, orientation and tensile properties of F100BCy and
      F100MBCx-y fiber specimens were performed. 

PMID- 24299743
TI  - Characteristics of starch-based biodegradable composites reinforced with date
      palm and flax fibers.
AB  - The aim of this work is to study the behavior of completely biodegradable starch
      based composites containing date palm fibers in the range from 20 to 80 wt%.
      Hybrid composites containing date palm and flax fibers, 25 wt% each, were also
      examined. The composites were preheated and then hot pressed at 5 MPa and 160
      degrees C for 30 min. SEM investigation showed strong adhesion between fibers and
      matrix. Density measurements showed very small void fraction (less than 0.142%)
      for composites containing up to 50 wt% fiber content. Increasing fiber weight
      fraction up to 50 wt% increased the composite static tensile and flexural
      mechanical properties (stiffness and strength). Composite thermal stability,
      water uptake and biodegradation improved with increasing fiber content. The
      present work shows that starch-based composites with 50 wt% fibers content have
      the optimum mechanical properties. The hybrid composite of flax and date palm
      fibers, 25 wt% each, has good properties and provides a competitive eco-friendly
      candidate for various applications.

PMID- 24299744
TI  - Degradation behavior of biocomposites based on cassava starch buried under indoor
      soil conditions.
AB  - Degradation of cassava (tapioca) starch based composite films during indoor soil
      burial experiments was analyzed using five factors, three levels Box-Behnken
      response surface design. From the results, it was observed that, increased water
      sorption promotes the entry of soil microorganism and it utilizes the starch
      films as a source of energy for their growth. The reduction in weight and
      mechanical property was associated with preferential loss of matrix components of
      the films. The microorganisms associated with the degradation of films were
      quantified and identified. Scanning electron microscopy (SEM) analysis showed the
      formation of patterns and cracks on the surface of the materials aged in the
      soils. From the results, second order polynomial models were developed for the
      responses. The results of the study demonstrated that, the tapioca starch based
      composites were showed a limited lifetime in biotic environment which make them
      suitable for being disposed in landfills after their use. 

PMID- 24299745
TI  - Characterisation and anti-biofilm activity of extracellular polymeric substances
      from Oceanobacillus iheyensis.
AB  - Oceanobacillus iheyensis BK6, isolated from a marine natural biofilm, produced
      approximately 40 0mg L(-1) extracellular polymeric substances (EPS). FTIR
      analysis of the EPS revealed different functional groups (halide groups, uronic
      acid and saccharides). The GCMS showed that the extracellular polysacchrides
      comprised of mannose (47.78%), glucose (29.71%) and arabinose (22.46%). The
      molecular mass of the EPS was about 2.14 * 10(6)Da. It was thermally stable and
      showed pseudoplastic rheology and emulsifying activity (66.47%). The EPS
      exhibited antibiofilm activity against a pathogenic strain of Staphylococcus
      aureus. This is the first report on the characterisation of EPS from the genus
      Oceanobacillus. The high viscosity, emulsifying properties and antibiofilm
      activity of EPS make it suitable for potential pharmaceutical and industrial
      applications.

PMID- 24299746
TI  - Peptide-decorated polyvinyl alcohol/hyaluronan nanofibers for human induced
      pluripotent stem cell culture.
AB  - Realization of the full potential of human induced pluripotent stem cells
      (hiPSCs) in clinical applications requires development of well-defined conditions
      for their growth and differentiation. A novel fully defined polyvinyl
      alcohol/hyaluronan (PVA/HA) polysaccharide nanofiber was developed for hiPSCs
      culture in commercially available xeno-free, chemically defined medium.
      Vitronectin peptide (VP) was immobilized to PVA/HA nanofibers through NHS/EDC
      chemistry. The hiPSCs successfully grew and proliferated on the VP-decorated
      PVA/HA nanofibers, similar to those on MatrigelTM. Such well-defined, xeno-free
      and safe nanofiber substrate that supports culture of hiPSCs will not only help
      to accelerate the translational perspectives of hiPSCs, but also provide a
      platform to investigate the cell-nanofiber interaction mechanisms that regulate
      stem cell proliferation and differentiation. 

PMID- 24299747
TI  - Application of quantum descriptors for predicting adsorption performance of
      starch and cyclodextrin adsorbents.
AB  - Adsorption trend of aromatic compounds on epichlorohydrin (EPI), 1,6
      hexamethylene diisocyanate (HDI), and 4,4-methylene diphenyl diisocyanate (MDI)
      cross-linked starch and cyclodextrin adsorbents were comparatively studied by
      density functional theorem (DFT) based interaction descriptors and batch
      adsorption studies. The DFT quantum chemical descriptors predicted adsorption
      trend of MDI adsorbents>HDI adsorbents>EPI adsorbents. The values of the
      fractional number of electrons transferred (DeltaN) for all the studied adsorbent
      adsorbate pair were negative, indicating that the adsorbents were electron donors
      in the studied adsorption interaction. The batch adsorption performance for the
      studied cross-linked adsorbents was in agreement with the DFT predictions. Energy
      gap, chemical hardness, and softness showed good linear correlation (R(2)=0.8,073
      +/- 0.2259) to the batch adsorption performance for most of the studied adsorbent
      adsorbate pairs. The present study demonstrated that DFT quantum chemical
      parameters are suitable adsorption descriptors for predicting adsorption
      performance of cross-linked adsorbents.

PMID- 24299748
TI  - Biosorption of Cu(2+), Pb(2+) and Cr(6+) by a novel exopolysaccharide from
      Arthrobacter ps-5.
AB  - The biosorption behaviors and mechanisms for Cu(2+), Pb(2+) and Cr(6+) by a novel
      exopolysaccharide (EPS) from Arthrobacter ps-5 have been studied in the paper.
      The influences of EPS concentration, solution pH and ionic strength on adsorption
      property were investigated. The EPS showed strong biosorption capability, up to
      169.15mg/g of Cu(2+), 216.09mg/g of Pb(2+) and 84.47mg/g of Cr(6+), respectively.
      With the additional concentration of Ca(2+) and K(+) increased, the biosorption
      ability on Cu(2+), Pb(2+) and Cr(6+) decreased significantly and followed the
      order of K(+)<Ca(2+). Infrared spectrometry analysis demonstrated that the groups
      of OH, CO, COC and COC of the EPS involved in metal biosorption process were the
      main functional groups for binding metal ions. 

PMID- 24299749
TI  - Optimization of the fermentation conditions of Rhizopus japonicus M193 for the
      production of chitin deacetylase and chitosan.
AB  - To improve the production of chitin deacetylase (CDA) for the bioconversion of
      chitin to chitosan with desirable functionality, the effect of the nutritional
      requirement on the CDA production from Rhizopus japonicus M193 fermentation was
      investigated under submerged conditions. Nutritional elements including glucose
      (g/L), inoculum level (%), and MgSO4.7H2O (g/L), as well as culture time (d) were
      identified as the most critical factors for the CDA production based on the
      results from Plackett-Burman design (PBD). Taguchi design with orthogonal array
      was further employed to optimize R. japonicus M193 fermentation conditions based
      on the results from PBD, in which 2.5% chitin, 5 g/L glucose, 5% inoculum level,
      0.6g/L MgSO4.7H2O, and 5d culture time were identified as the optimal
      fermentation conditions. Under this condition, the maximum CDA production, DDA
      and MM of produced chitosan were 547.38 +/- 12.06 U/L, 78.85 +/- 1.68%, and
      125.63 +/- 3.74 kDa, respectively. Obtained chitosan displayed similar
      physicochemical and structural properties to those of commercial chitosan
      extracted using chemical method based on the results from Fourier transform
      infrared spectrometer (FT-IR), thermogravimetric analysis (TGA)-differential
      scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) assays, while
      the use of chemical reagents was significantly reduced.

PMID- 24299750
TI  - Electrospinning and characterization of chitin nanofibril/polycaprolactone
      nanocomposite fiber mats.
AB  - Nanocomposite fiber mats based on biodegradable polycaprolactone (PCL) and chitin
      nanofibril (n-chitin) were produced via electrospinning. The morphologies,
      thermal and mechanical properties as well as surface wettability of the fiber
      mats were studied by scanning electron microscopy, differential scanning
      calorimetry analysis, thermogravimetric analysis, dynamic mechanical analysis and
      static water-contact-angle analysis, respectively. The addition of chitin
      nanofibrils into PCL resulted in a small change in thermal behavior, but a
      significant improvement in mechanical properties. Moreover, the surface
      wettability of electrospun fiber mats transformed from hydrophobicity to
      hydrophilicity when the chitin nanofibril content was more than 25 wt%. In
      addition, in vitro cell culture results indicated that the addition of chitin
      nanofibrils can strongly improve the cellular infiltration and migration
      confirming that the chitin nanofibril was a good reinforcing as well as bioactive
      filler for PCL.

PMID- 24299751
TI  - Use of carboxylated cellulose nanofibrils-filled magnetic chitosan hydrogel beads
      as adsorbents for Pb(II).
AB  - Novel magnetic hydrogel beads (m-CS/PVA/CCNFs), consisting of carboxylated
      cellulose nanofibrils (CCNFs), amine-functionalized magnetite nanoparticles and
      poly(vinyl alcohol) (PVA) blended chitosan (CS), were prepared by an
      instantaneous gelation method. SEM, XRD, and TGA techniques were applied to
      investigate the structure of the hydrogel materials. The magnetic hydrogels were
      employed as absorbents for removal of Pb(II) ions from aqueous solutions and the
      fundamental adsorption behavior was studied. Experimental results revealed that
      the m-CS/PVA/CCNFs hydrogels exhibit higher adsorption capacity with the value of
      171.0mg/g, and the carboxylate groups on the CCNFs surface play an important role
      in Pb(II) adsorption. Moreover, adsorption isotherm data were reliably described
      by the Langmuir model and the adsorption kinetics closely followed pseudo-second
      order model. Additionally, the Pb(II)-loaded m-CS/PVA/CCNFs hydrogels could be
      easily regenerated in weak acid solution and the adsorption effectiveness of 90%
      can be maintained after the 4 cycles. 

PMID- 24299752
TI  - Preparation of CMC-modified melamine resin spherical nano-phase change energy
      storage materials.
AB  - A novel carboxymethyl cellulose (CMC)-modified melamine-formaldehyde (MF) phase
      change capsule with excellent encapsulation was prepared by in situ
      polymerization. Effects of CMC on the properties of the capsules were studied by
      Fourier transformation infrared spectroscopy (FTIR), differential scanning
      calorimetry (DSC), scanning electronic microscopy (SEM), X-ray diffractometry
      (XRD), and thermogravimetric analysis (TGA). The results showed that the CMC
      modified capsules had an average diameter of about 50nm and good uniformity. The
      phase change enthalpy of the capsules was increased and the cracking ratio
      decreased by incorporating a suitable amount of CMC. The optimum phase change
      enthalpy of the nanocapsules was 83.46J/g, and their paraffin content was 63.1%.
      The heat resistance of the capsule shells decreased after CMC modification. In
      addition, the nanocapsule cracking ratio of the nanocapsules was 11.0%, which is
      highly attractive for their application as nano phase change materials. 

PMID- 24299753
TI  - Production optimization and expression of pectin releasing enzyme from
      Aspergillus oryzae PO.
AB  - Protopectinase is an enzyme that solubilizes protopectin forming highly
      polymerized soluble pectin. Protopectinase activity was detected from Aspergillus
      oryzae PO isolated from soil of persimmon orchard. Response surface methodology
      of Box-Behnken Design with three fermentation variables (temperature, NaNO3 and
      apple pomace concentration) was used to optimize protopectinase production of A.
      oryzae PO, and protopectinase activity was improved to 270.0 U/ml. Endo
      polygalacturonase belonged to A-type PPase from A. oryzae PO was cloned and
      expressed in Pichia pastoris GS115. The endo-polygalacturonase expression was
      0.418 mg/ml and the specific activity of purified recombinant endo
      polygalacturonase was 7520 U/mg toward polygalacturonic acid. The optimal
      temperature and pH of recombinant endo-polygalacturonase were 45 degrees C and
      5.0, respectively. The recombinant endo-polygalacturonase activity was enhanced
      by the presence of Mg(2+), while Ca(2+), Ni(2+) Mn(2+), Cu(2+) and SDS strongly
      inhibited the enzyme activity. The apparent Km value and Vmax value were 5.59
      mg/ml and 1.01 MUmol/(minml), respectively.

PMID- 24299754
TI  - Hyaluronic acid and alginate covalent nanogels by template cross-linking in
      polyion complex micelle nanoreactors.
AB  - Hyaluronic acid (HA) and alginate (AL) covalent nanogels cross-linked with l
      lysine ethyl ester were prepared by template chemical cross-linking of the
      polysaccharide in polyion complex micelle (PIC) nanoreactors. By using this
      method we were able to prepare HA and AL nanogels without organic solvents. PICs
      were prepared by using poly(ethylene oxide)-block-poly[(3-acrylamidopropyl)
      trimethylammonium chloride] (PEO-b-PAMPTMA) or poly[(N-isopropylacrylamide)-block
      PAMPTMA] (PNIPAAM-b-PAMPTMA). Only PNIPAAM-b-PAMPTMA block copolymers allowed to
      prepare PIC with small and controlled size. Short polysaccharide chains (Xn=50
      and 63 for AL and HA, respectively, where Xn is the number of monosaccharidic
      units present in the polysaccharide) where used to optimize PIC formation. The
      remarkable difference in charge density and rigidity of HA and AL did not have a
      significant influence on the formation of PICs. PICs with small size (diameter of
      about 50-80 nm) and low polydispersity were obtained up to 5mg/mL of polymer.
      After cross-linking with l-lysine ethyl ester, the nanoreactors were dissociated
      by adding NaCl. The nanogels were easily purified and isolated by dialysis. The
      dissociation of the nanoreactors and the formation of the nanogels were confirmed
      by (1)H NMR, DLS, TEM and zeta-potential measurements. The size of the smallest
      nanogels in solution in the swollen state was 50-70 nm in presence of salt and 80
      100 nm in water.

PMID- 24299755
TI  - Design and formulation of trimethylated chitosan-graft-poly(epsilon-caprolactone)
      nanoparticles used for gene delivery.
AB  - The ideal gene polyplexes should have a subtle balance between polyplex stability
      to protect DNA against nucleases, and polyplex instability to permit DNA
      dissociation inside cells. In this research, low molecular weight trimethylated
      chitosan was chemically modified with poly(epsilon-caprolactone). Owing to the
      amphiphilic character, trimethylated chitosan-graft-poly(epsilon-caprolactone)
      (TMC-g-PCL) formed nanoparticles in aqueous media. TMC-g-PCL nanoparticles could
      effectively condense pDNA into polyplexes about 200 nm in size. The TMC-g-PCL/DNA
      polyplexes were stable in physiological salt condition and showed high uptake
      efficiency probably due to the increasing cell membrane-carrier interaction as a
      result of hydrophobic modification. However, the high degree of quaternization
      influenced the buffer capacity of TMC-g-PCL and led to a reduction in the release
      from the lysosomes. By adding chloroquine to exclude the limitation of lysosome
      escape, the transfection efficiency of TMC-g-PCL/DNA polyplexes was similar to
      that of PEI/DNA polyplexes. This study demonstrated the potential of TMC-g
      PCL/DNA nanoparticles as an efficient carrier for gene delivery.

PMID- 24299756
TI  - Water soluble folate-chitosan nanogels crosslinked by genipin.
AB  - Folate-chitosan conjugates were prepared by a concurrent functionalization and
      crosslinking reaction with the natural crosslinker genipin. Genipin molecule was
      employed simultaneously as crosslinker agent and spacer molecule in order to
      allow the functionalization with folic acid for active tumor targeting. The
      reaction was carried out in reverse microemulsion which provided colloidal size
      and monodisperse particle size distribution. The water solubility of the obtained
      folate-genipin-chitosan nanogels was studied as function of the pH of the medium
      and all nanoparticles were totally dispersible at physiological pH. The enzymatic
      degradability of the nanogels in a lysozyme solution was evaluated at acidic and
      physiological pH. QELS analyses of the swelling behavior of the nanogels with the
      pH did not show a clear pH-sensitivity. However, the study on the loading and
      release capacity of 5-fluorouracil revealed an interesting pH-responsive behavior
      of the nanogels that makes them promising as nanodevices for targeted anticancer
      drug delivery. 

PMID- 24299757
TI  - Cyclodextrins as encapsulation agents for plant bioactive compounds.
AB  - Plants possess a wide range of molecules capable of improve healing: fibre,
      vitamins, phytosterols, and further sulphur-containing compounds, carotenoids,
      organic acid anions and polyphenolics. However, they require an adequate level of
      protection from the environmental conditions to prevent losing their structural
      integrity and bioactivity. Cyclodextrins are cyclic oligosaccharides arising from
      the degradation of starch, which can be a viable option as encapsulation
      technique. Cyclodextrins are inexpensive, friendly to humans, and also capable of
      improving the biological, chemical and physical properties of bioactive
      molecules. Therefore, the aim of this review is to highlight the use of
      cyclodextrins as encapsulating agents for bioactive plant molecules in the
      pharmaceutical field. 

PMID- 24299758
TI  - Interactions between carboxymethyl konjac glucomannan and soy protein isolate in
      blended films.
AB  - To elucidate biopolymer interactions between carboxymethyl konjac glucomannan
      (CMKGM) and soy protein isolate (SPI) in different ratios on physicochemical
      properties of the blended films, biodegradable CMKGM/SPI films were prepared and
      characterized. The results showed that CMKGM and SPI are highly compatible in
      blended film formation, and that Maillard reactions and hydrogen bonds
      interactions between CMKGM and SPI occurred. The water adsorption of the
      CMKGM/SPI films progressively decreased with increasing CMKGM level, the surface
      wettability of the blended films was improved with increasing CMKGM content; the
      CMKGM/SPI blend films had enhanced tensile strength (TS) and elongation at break
      (EAB) compared to pure CMKGM and SPI films; the oxygen permeability of blend
      films was decreased; the roughness was decreased with increasing CMKGM content.
      Moreover, the CMKGM/SPI film was biocompatible and biodegradable. 

PMID- 24299759
TI  - Stability assessment of hypromellose acetate succinate (HPMCAS) NF for
      application in hot melt extrusion (HME).
AB  - HPMCAS is a widely used polymer in the pharmaceutical industry as an excipient.
      In this work, the physicochemical stability of HPMCAS was investigated for hot
      melt extrusion (HME) application. The reduction in zero rate viscosity (eta0) of
      the polymer with the increase in temperature was determined using rheological
      evaluation prior to HME processing. The energy of activation for AS-MF determined
      by fitting Arrhenius model to the temperature dependent reduction in eta0 was
      found to be slightly lower than that for the other grades of HPMCAS. Glassy
      yellowish HMEs were obtained using Haake Mini-Lab MicroCompounder operated at
      160, 180, and 200 degrees C and 100, 200, and 300 rpm for all the grades at each
      temperature. Various physicochemical properties of HPMCAS such as glass
      transition temperature, semi-crystalline nature, solid state functional group
      properties, moisture content, and solution viscosity were not significantly
      affected by the HME processing. The most significant change was the release of
      acetic and succinic acid with the increase in HME temperature and speed. The free
      acid content release due to HME was directly proportional to the speed at lower
      operating temperatures. AS-LF was found to be the most stable with the lowest
      increase in total free acid content even at higher HME temperature and speed.
      Although the dissolution time was not affected due to HME for AS-LF and AS-MF
      grades, it was notably increased for AS-HF, perhaps due to significant reduction
      of succinoyl content. In conclusion, the HME processing conditions for solid
      dispersions of HPMCAS should be based on the acceptance levels of free acid for
      the drug and the drug product.

PMID- 24299760
TI  - In vitro digestibility, physicochemical, thermal and rheological properties of
      banana starches.
AB  - Banana starches (BS) were isolated from Enano, Morado, Valery and Macho
      cultivars. The BS possessed B-type crystallinity and an amylose content varying
      from 19.32 to 26.35%. Granules had an oval morphology with different major-to
      minor axis ratios, exhibiting both mono- and bi-modal distributions and mean
      particle sizes varying from 32.5 to 45 MUm. BS displayed zeta-potential values
      ranging between -32.25 and -17.32 mV, and formed gels of incipient to moderate
      stability. The enthalpy of gelatinization of BS affected the crystalline order
      stability within the granules. In-vitro digestibility tests showed fractions as
      high as 68% of resistant starch. Rheological oscillatory tests at 1 Hz showed
      that BS dispersions (7.0%, w/w) exhibited Type III behaviour, attributed to the
      formation of a continuous phase complex three-dimensional amylose gel reinforced
      by swollen starch granules acting as fillers. Amylose content and granules
      morphology were the main factors influencing the BS properties.

PMID- 24299761
TI  - Qualitative and quantitative assessment of water sorption in natural fibres using
      ATR-FTIR spectroscopy.
AB  - In the field of composite materials, natural fibres appear to be a viable
      replacement for glass fibres. However, in humid conditions, strong hydrophilic
      behaviour of such materials can lead to their structural modification. Then,
      understanding moisture sorption mechanisms in these materials is an important
      issue for their efficient use. In this work, the water sorption on three natural
      fibres (flax, hemp and sisal) was studied using Fourier transformed infrared
      spectroscopy. The spectral information allowed both qualitative and quantitative
      analyses of the moisture absorption mechanisms. The main chemical functions
      involved in the water sorption phenomenon were identified. The absolute water
      content of the fibres was also determined by using a partial least square
      regression (PLS-R) approach. Moreover, typical sorption isotherm curves described
      by Park model were fitted as well as water diffusion kinetics. These last
      applications confirmed the validity of the FTIR spectra based predictive models. 

PMID- 24299762
TI  - Thermosensitive methyl cellulose-based injectable hydrogels for post-operation
      anti-adhesion.
AB  - Thermosensitive methyl cellulose (MC)-based injectable hydrogels for post
      operation anti-adhesion were prepared by integrating polyethylene glycol (PEG),
      carboxymethyl cellulose (CMC) and chitosan sulfate (CS-SO3) with MC sols. The
      viscosity of the MC-based sols depended on the sol composition, especially the
      amount of CMC. The gelation temperature of the sols was tuned by adjusting the
      concentrations of K(+) and other components to obtain an MC-based sol that
      transformed to a gel at body temperature. The composition of the sol also
      affected the gel strength. Adding PEG decreased the repulsions between the CMC
      and CS-SO3 macromolecules and thus increased the gel strength. The efficacy of
      the MC-based injectable hydrogels as barriers for reducing postsurgical adhesions
      was evaluated using a rat cecal abrasion model. The PEG and CS-SO3 loaded MC
      based injectable hydrogels were effective in reducing adhesion formation and
      reduced adhesiolysis difficulties. 

PMID- 24299763
TI  - Hollow latex particles functionalized with chitosan for the removal of
      formaldehyde from indoor air.
AB  - Chitosan and polyethyleneimine (PEI) functionalized hollow latex (HL) particles
      were conveniently fabricated by coating poly(methyl methacrylate-co-divinyl
      benzene-co-acrylic acid) (P(MMA/DVB/AA)) HL particles with 5 wt% chitosan or 14
      wt% PEI. The materials were used as formaldehyde adsorbent, where their adsorbent
      activity was examined by Fourier Transform Infrared (FTIR) spectroscopy. The
      nucleophilic addition of amines to carbonyls generated a carbinolamine
      intermediate with a characteristic band at 1,020 cm(-1) and Schiff base product
      at 1650 cm(-1), whose intensity increased with prolonged formaldehyde exposure
      times. The major products observed in HL-chitosan were carbinolamine and Schiff
      base, whereas a small amount of Schiff base was obtained in HL-PEI particles,
      confirming a chemical bond formation without re-emission of formaldehyde.
      Compared to HL-PEI, HL-chitosan possesses higher formaldehyde adsorption
      efficiency. Besides providing opacity and whiteness, the multilayer HL-chitosan
      particles can effectively remove indoor air pollutants, i.e., formaldehyde gas,
      and, hence, would be useful in special coating applications.

PMID- 24299764
TI  - Structural and immunological studies of an exopolysaccharide from Acinetobacter
      junii BB1A.
AB  - A water-soluble heteropolysaccharide (PS) was isolated from extracellular
      polymeric substances (EPS) produced by a novel metal tolerant bacterium,
      Acinetobacter junii BB1A. Sugar analysis showed that the PS was composed of
      mannose, galactose and arabinose in a molar ratio of nearly 3:1:1. Structural
      characterization of the PS was carried out using methylation analysis, periodate
      oxidation, Smith degradation and 1D/2D NMR experiments. Methylation analysis
      revealed that the PS was consisted of 2,4-linked-mannopyranosyl, 3,4-linked
      mannopyranosyl, 2-linked-galactopyranosyl, terminal mannopyranosyl and
      arabinopyranosyl residues in a relative proportion of nearly 1:1:1:1:1. Smith
      degradation of the PS showed the presence of hydrated glyceraldehyde containing
      disaccharide unit consisting of alpha-d-Manp-(1->and->4)-alpha-d-Manp-(1
      >residues where the later was directly attached to a hydrated glyceraldehyde
      moiety. This polysaccharide showed significant in vitro splenocyte, thymocyte,
      and macrophage activations with optimum dose of 100 MUg/mL for macrophage and 25
      MUg/mL both for the splenocyte and thymocyte.

PMID- 24299765
TI  - Optimization of hot-compressed water pretreatment of bagasse and characterization
      of extracted hemicelluloses.
AB  - Developing optimum treatment and separation procedures for hemicellulose
      components of lignocellulosic biomass could be useful in ethanol fermentation
      processes and obtaining pure hemicelluloses as biopolymers. Sugarcane bagasse
      analyses indicate that xylose is the major hemicellulose component constituting
      17.7% of dry bagasse weight. In this study the effects of treatment conditions
      such as time, temperature and pressure on the yields of extracted hemicelluloses
      were studied. The optimum conditions were achieved at 180  degrees C for 30 min
      and 1 MPa pressure, with the yield of xylose reaching to 85% and the
      concentrations of sugar degradation products such as HMF and furfural remaining
      minimal at 0.95 and 0.07 g/L, respectively. Further, isolation of hemicelluloses
      from extracted hemicelluloses solutions was performed using Alfa Laval M20
      membrane filtration system in two steps: (1) concentration of high molar mass
      hemicelluloses by ultrafiltration; and (2) separation of low molar mass
      hemicelluloses and oligomeric sugars by nanofiltration. The isolated
      hemicelluloses with the optimum pretreatment conditions were characterized by FT
      IR and (13)C NMR techniques, resulting in agreement with typical spectra of xylan
      type hemicelluloses.

PMID- 24299766
TI  - Relationship between structure and cytocompatibility of divinyl sulfone cross
      linked hyaluronic acid.
AB  - Hyaluronic acid (HA), a carbohydrate polymer naturally found in the eye, has been
      chemically modified by cross-linking to enhance its performance as a drug
      carrier. Although the treatment of HA with divinyl sulfone (DVS) is reported, the
      effects of cross-linker concentration on the biomaterial-mediated retinal pigment
      epithelial (RPE) cellular responses are yet to be investigated. This paper
      explores, for the first time, the relationship between molecular structure and
      cytocompatibility of HA hydrogels cross-linked with DVS of varying concentrations
      (0-100mM). The results showed that with increasing DVS concentration, the sulfur
      content and sulfonyl-bis-ethyl cross-link amount are increased and the mechanical
      stability and resistance against enzymatic degradation are enhanced, indicating
      the crucial role of cross-linker in the alteration of structure and property of
      this polysaccharide biomaterial. The cell viability, pro-inflammatory gene and
      cytokine expression, and glutamate uptake were suggested to be indicative of
      cytocompatibility and found to be strongly dependent on the cross-linker
      concentration. 

PMID- 24299767
TI  - Extraction, preliminary characterization and antioxidant activity of Se-enriched
      Maitake polysaccharide.
AB  - A Se-enriched Grifola frondosa polysaccharide (Se-GP) was obtained from G.
      frondosa enriched with Se by spraying an Na2SeO3 solution during fruit body
      growth using a Box-Behnken design and compared to G. frondosa polysaccharide (GP)
      for preliminary characterization and determination of the antioxidant activity.
      Under optimal conditions, polysaccharide yields and both the Se-GP and GP
      contents do not differ; however, the Se content of Se-GP (17.52 MUg/g) was 48.7
      times that of GP. Three homogenous Se-GPs (Se-GP11, Se-GP22 and Se-GP33) or GPs
      (GP11, GP22 and GP33) were obtained via DEAE-52 and Sephacryl S-400 purification.
      Their molecular weight and polysaccharide content of these compounds were not
      obviously different, whereas the Se content of Se-GP11, Se-GP22 and Se-GP33 was
      9.41, 6.59 and 16.25 times that of GP11, GP22 and GP33, respectively. The
      antioxidant activity of Se-GP for the DPPH, ABTS and hydroxyl radicals was higher
      than that of GP and was highest for the hydroxyl radical.

PMID- 24299768
TI  - Development of calcium pectinate-tamarind seed polysaccharide mucoadhesive beads
      containing metformin HCl.
AB  - Novel mucoadhesive beads containing metformin HCl made of low methoxy (LM) pectin
      tamarind seed polysaccharide (TSP) polymer-blend was developed through ionotropic
      gelation technique and optimized using 3(2) factorial design. Effects of LM
      pectin and TSP amounts on drug encapsulation efficiency (DEE), and cumulative
      drug release at 10h (R10h) were analyzed using response surface methodology. The
      optimized calcium pectinate-TSP beads containing metformin HCl showed DEE of
      95.12 +/- 4.26%, R10h of 46.53 +/- 3.28%, and mean diameter of 1.93 +/- 0.26 mm.
      The in vitro drug release from these beads was followed controlled-release (zero
      order) pattern with super case-II transport mechanism. These beads were also
      characterized by SEM and FTIR. The optimized beads also exhibited pH-dependent
      swelling, good mucoadhesivity with goat intestinal mucosa and significant
      hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after
      oral administration.

PMID- 24299769
TI  - Photopolymerisation and characterization of maleylatedcellulose-g-poly(acrylic
      acid) superabsorbent polymer.
AB  - A novel biodegradable superabsorbent polymer has been prepared from maleylated
      cotton stalk cellulose (MCSC) crosslinker and acrylic acid (AA) by ultraviolet
      (UV) photopolymerization in aqueous solution at room temperature, and irgacure
      651 as a photoinitiator. The resulting superabsorbent was characterized by FT-IR,
      (1)H NMR, SEM and TGA. The effects of preparation conditions such as degree of
      substitution (DS), amount of maleylated cotton stalk cellulose, exposed time,
      photoinitiator amount and monomer concentration on the water absorbency and the
      monomer conversion in graft were evaluated. The swelling kinetics, salt
      resistance, water retention capacity and biodegradability of the MCSC-g-PAA
      superabsorbent were investigated. It was found that, the obtained superabsorbent
      have good swelling degree that greatly affected by its composition and
      preparation conditions. Owing to its considerable good water retention capacity,
      being economical and environment-friendly, it might be useful for its application
      in agriculture field. 

PMID- 24299770
TI  - The effect of alginate on DNA delivery from layer-by-layer assembled films.
AB  - Alginate has been previously utilized as an adjuvant in nanoparticle-mediated
      gene delivery. In this study, we investigated the extent to which alginate
      promotes in situ transfection from polyelectrolyte multilayers (PEMs). After
      spiking free alginate molecules, DNA release from PEMs was increased and
      transgene expression was enhanced, suggesting that alginate may compete with DNA
      to weaken electrostatic interaction within PEMs. Consequently, alginate was
      applied to compose multilayers with DNA and polyethyleneimine (PEI).
      Interestingly, the incorporated alginate increased not only deposition but also
      delivery of DNA from PEMs. Quartz crystal microbalance (QCM) analysis suggested
      that the deposited alginate enhanced PEI adsorption which in turn augmented
      subsequent DNA deposition. In situ transfection experiments revealed that
      alginate within PEMs improved not only the level but also the duration of
      transgene expression. This system should be a potential strategy to regulate gene
      delivery from scaffolds for tissue engineering application. 

PMID- 24299771
TI  - Surfactant-aided electrospraying of low molecular weight carbohydrate polymers
      from aqueous solutions.
AB  - In this work it is demonstrated, for the first time, that it is feasible to
      develop, using the electrospraying technique, low molecular weight carbohydrate
      based capsule morphologies from aqueous solutions through the rational use of
      surfactants. Two different low molecular weight carbohydrate polymers were used,
      a maltodextrin and a commercial resistant starch. The solution properties and
      subsequent high voltage sprayability was evaluated upon addition of non-ionic
      (Tween20, and Span20) and zwitterionic (lecithin) surfactants. The morphology and
      molecular organization of the structures obtained was characterized and related
      to the solution properties. Results showed that, while unstable jetting and
      dropping occurred from the pure carbohydrate solutions without surfactant, the
      addition of some surface active molecules above their critical micelle
      concentration facilitated capsule formation. Higher surfactant concentrations led
      to smaller and more homogeneous capsule morphologies, related to lower surface
      tension and higher conductivity of the solutions. 

PMID- 24299772
TI  - Thermal stability of spent coffee ground polysaccharides: galactomannans and
      arabinogalactans.
AB  - In order to better understand the thermal stability of spent coffee grounds (SCG)
      galactomannans and arabinogalactans and the reactions that can occur upon
      roasting, long term isothermal exposures, up to 3h, were performed at 160, 180,
      200, 220, and 240  degrees C. The resultant products were analysed according to
      the sugars and linkage composition and also by electrospray mass spectrometry.
      Galactomannans did not loss mass at T <= 200  degrees C during exposures up to 3h
      whereas the arabinogalactans showed that thermal stability only for T <= 180 
      degrees C. This was in accordance with the estimated activation energies of their
      thermal decomposition of 138 kJ/mol and 94 kJ/mol, respectively. The roasting of
      galactomannans promoted the formation of new glycosidic linkages, with occurrence
      of 2-, 6-, 2,3-, 2,6-, 3,6-, 2,3,6-, 3,4,6-linked mannose residues, 3,4,6-linked
      galactose residues, and terminally-linked glucose residues, observed by
      methylation analysis. Depolymerisation and formation of anhydrohexose residues at
      the reducing end and mannose-glucose isomerisation were also observed. The
      roasting of galactomannans at 200  degrees C promoted their solubility in water
      upon alkali extraction and neutralisation.

PMID- 24299773
TI  - Metal removal of cyanobacterial exopolysaccharides by uronic acid content and
      monosaccharide composition.
AB  - In the present study, chromium, cadmium and metal mixed (chromium+cadmium)
      removal and its association with exopolysaccharides and uronic acids production
      in Synechocystis sp. BASO671 were investigated. It was investigated that BASO671
      showed different removal ability when exposed to each metal solely and mixed
      metal. EPS production by BASO671 was increased following exposure to 15 and 35
      ppm Cr(VI), Cd(II) and Cr(VI)+Cd(II). Monomer composition of EPS was changed
      after metal treatment. Uronic acid contents of metal treated cells were higher
      than control cells of each isolate. Also, glucuronic acid content and galactronic
      acid content of EPS correlated with uronic acid contents of cells. Scanning
      electron microscopy and energy dispersive X-ray spectroscopy analysis confirmed
      that a considerable amount of metals had precipitated on the cell surface.
      Fourier transform infrared spectrum analysis of EPSs indicated the presence of CH
      and CO group, which may serve as binding sites for divalent cations.

PMID- 24299774
TI  - High strength of hemicelluloses based hydrogels by freeze/thaw technique.
AB  - Novel hydrogels were prepared from hemicelluloses, polyvinyl alcohol (PVA), and
      chitin nanowhiskers through 0, 1, 3, 5, 7, and 9 times of freeze/thaw cycle.
      These hydrogels were characterized by Fourier transform infrared spectroscopy (FT
      IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermo
      gravimetric analysis (TGA), swelling property, and compressive strength. The
      repeated freeze/thaw cycles induced physically crosslinked chains packing among
      these polymers, and a phase separation caused by the hydrogen bonds. Larger pores
      led to a high swelling degree, whereas the formation of compact structure after
      multiple freeze/thaw cycles resulted in high mechanical strength and thermal
      stability. The highest compressive strength of these hydrogels was achieved by
      the 9 times of freeze/thaw cycles with compressive stress of 10.5 MPa. This work
      provides a remarkable way for the preparation of hydrogels with good mechanical
      properties by physical method.

PMID- 24299775
TI  - Carbohydrate composition of compost during composting and mycelium growth of
      Agaricus bisporus.
AB  - Changes of plant cell wall carbohydrate structures occurring during the process
      to make suitable compost for growth of Agaricus bisporus are unknown. In this
      paper, composition and carbohydrate structures in compost samples collected
      during composting and mycelium growth were analyzed. Furthermore, different
      extracts of compost samples were prepared with water, 1M and 4M alkali and
      analyzed. At the beginning of composting, 34% and after 16 days of mycelium
      growth 27% of dry matter was carbohydrates. Carbohydrate composition analysis
      showed that mainly cellulose and poorly substituted xylan chains with similar
      amounts and ratios of xylan building blocks were present in all phases studied.
      Nevertheless, xylan solubility increased 20% over the period of mycelium growth
      indicating partial degradation of xylan backbone. Apparently, degradation of
      carbohydrates occurred over the process studied by both bacteria and fungi,
      mainly having an effect on xylan-chain length and solubility. 

PMID- 24299776
TI  - Structural and functional properties of C-type starches.
AB  - This study investigated the structural and functional properties of C-type
      starches from pea seeds, faba bean seeds, yam rhizomes and water chestnut corms.
      These starches were mostly oval in shape with significantly different sizes and
      contents of amylose, damaged starch and phosphorus. Pea, faba bean and water
      chestnut starches had central hila, and yam starch had eccentric hilum. Water
      chestnut and yam starches had higher amylopectin short and long chain,
      respectively. Water chestnut and faba bean starches showed CA-type
      crystallinities, and pea and yam starches had C-type crystallinities. Water
      chestnut starch had the highest swelling power, granule swelling and pasting
      viscosity, lowest gelatinization temperatures and enthalpy. Faba bean starch had
      the lowest pasting viscosity, whereas yam starch had the highest gelatinization
      temperatures. Water chestnut and yam starches possessed significantly higher and
      lower susceptibility to acid and enzyme hydrolysis, the highest and lowest RDS
      contents, and the lowest and highest RS contents, respectively. 

PMID- 24299777
TI  - Exopolysaccharides of Synechocystis aquatilis are sulfated arabinofucans
      containing N-acetyl-fucosamine.
AB  - Cyanobacteria are known to be a rather diverse group of organisms regarding e.g.
      morphology, metabolism and composition of excreted exopolysaccharides (EPS).
      Considering the high number of known cyanobacterial species the EPS from only a
      small percentage are investigated in detail. This work examined EPS from the
      unicellular strains of Synechocystis aquatilis and S. pevalekii with various
      methods. The results emphasize the heterogeneity of cyanobacterial EPS. S.
      pevalekii secrets complex hetero-polysaccharides and acidic proteins as
      proteoglycan-complexes whereas the protein-free but highly sulfated EPS from S.
      aquatilis only consist of 4 dominant monosaccharides. Especially remarkable is
      the composition of these EPS: an arabinofucan with higher amounts of N-acetyl
      fucosamine (FucNAc) and only minor quantities of glucose. Both EPS and the newly
      found component FucNAc in EPS from S. aquatilis extend the possible components of
      cyanobacterial EPS and the knowledge of heterogeneity of cyanobacterial
      metabolites. 

PMID- 24299778
TI  - Electro-spun organic nanofibers elaboration process investigations using
      comparative analytical solutions.
AB  - In this paper Enhanced Variational Iteration Method, EVIM is proposed, along with
      the BPES, for solving Bratu equation which appears in the particular elecotrospun
      nanofibers fabrication process framework. Elecotrospun organic nanofibers, with
      diameters less than 1/4 microns have been used in non-wovens and filtration
      industries for a broad range of filtration applications in the last decade.
      Electro-spinning process has been associated to Bratu equation through thermo
      electro-hydrodynamics balance equations. Analytical solutions have been proposed,
      discussed and compared. 

PMID- 24299779
TI  - Structure and anti-metapneumovirus activity of sulfated galactans from the red
      seaweed Cryptonemia seminervis.
AB  - The anti-HMPV (human metapneumovirus) activity was determined for sulfated dl
      hybrid galactans obtained from the red seaweed Cryptonemia seminervis and their
      depolymerized products obtained by reductive partial hydrolysis. Structural
      studies carried out in three homogeneous depolymerized fractions DS-1, DS-2e and
      DS-3 (Mw of 51.6-63.8 kDa) showed that these galactans present different chemical
      characteristics, as monosaccharide composition, content of sulfate groups (14.1
      29.9%) and agaran:carrageenan molar ratio diads, 2.7:1 for DS-1 and DS-2e and 1:1
      for DS-3. The sulfate groups are located principally on C-2 of beta-d
      galactopyranose and 4,6-O-(1'-carboxyethylidene)-beta-d-galactopyranose residues
      and on C-6 of alpha-galactose residues. Sulfated dl-galactans and their
      depolymerized products exhibited antiviral activity at a very early stage of the
      viral infection cycle. All fractions, except DS-2e inhibited HMPV replication by
      binding to the viral particle. Besides depolymerized galactans DS-2e and DS-3
      inhibited the recognition of cell receptor by HMPV and penetration to the host
      cell, respectively.

PMID- 24299780
TI  - Synthesis, characterization and non-isothermal decomposition kinetic of a new
      galactochloralose based polymer.
AB  - A glycopolymer, poly(3-O-methacroyl-5,6-O-isopropylidene-1,2-O-(S)
      trichloroethylidene-alpha-d-galactofuranose) (PMIPTEG) was synthesized from the
      sugar-carrying methacrylate monomer, 3-O-methacroyl-5,6-O-isopropylidene-1,2-O
      (S)-trichloroethylidene-alpha-d-galactofuranose (MIPTEG) via conventional free
      radical polymerization with AIBN in 1,4-dioxane. The structures of glycomonomer
      and their polymers were confirmed by UV-vis, FT-IR, (1)H NMR, (13)C NMR, GPC,
      TG/DTG-DTA, DSC, and SEM techniques. SEM images showed that PMIPTEG had a
      straight-chain length structure. On the other hand, the thermal decomposition
      kinetics of polymer were investigated by means of thermogravimetric analysis in
      dynamic nitrogen atmosphere at different heating rates. The apparent activation
      energies for thermal decomposition of the PMIPTEG were calculated using the
      Kissinger, Kim-Park, Tang, Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS)
      and Friedman methods and were found to be 100.15, 104.40, 102.0, 102.2, 103.2 and
      99.6 kJ/mol, respectively. The most likely process mechanism related to the
      thermal decomposition stage of PMIPTEG was determined to be a Dn deceleration
      type in terms of master plots results.

PMID- 24299781
TI  - Enzymolysis-ultrasonic assisted extraction, chemical characteristics and
      bioactivities of polysaccharides from corn silk.
AB  - An enzymolysis-ultrasonic assisted extraction (EUAE) procedure of corn silk
      polysaccharides (CSPS) was established and the physicochemical properties,
      antioxidant and anticancer activities of CSPS were studied. Orthogonal test and
      response surface methodology were applied to optimize the extraction parameters.
      The optimum enzymolysis and ultrasonic conditions were cellulase content of 7.5%
      for 150 min at 55  degrees C and liquid-solid ratio of 31.8 for 34.2 min at 66.3 
      degrees C, respectively. Under these conditions, the yield of CSPS increased from
      4.56% to 7.10%. CSPS obtained by hot water and EUAE were composed of rhamnose,
      arabinose, xylose, mannose, galactose and glucose with molecular ratios of
      4.17:17.33:5.59:18.65:19.11:35.14 and 8.83:15.77:7.92:12.39:11.15:43.94,
      respectively. Their molecular weight distributions were 10.52 * 10(4) and 6.88 *
      10(4)Da, respectively. CSPS obtained by EUAE showed morphological and
      conformation changes and higher antioxidant and anticancer activities compared
      with CSPS extracted by hot water.

PMID- 24299782
TI  - Interaction with bovine serum albumin of an anti-oxidative pectic arabinogalactan
      from Andrographis paniculata.
AB  - A pectic arabinogalactan was obtained from the leaves of Andrographis paniculata
      by aqueous extraction followed by alpha-amylase treatment, deproteination, and
      anion exchange chromatography. Methylation analysis, Smith degradation, and NMR
      spectroscopy indicated that it was a highly branched arabinogalactan containing a
      (1->3)-linked beta-d-Galp main chain, substituted at O-6 by (1->6)-linked beta-d
      Galp side chains. The latter residues were substituted at O-3 by (1->5)- and (1
      >3)-linked alpha-l-Araf chains, and non reducing end-units of alpha-l-Araf and
      beta-d-Galp. This homogeneous arabinogalactan (36 kDa), which contained phenolic
      acids, showed dose-dependent anti-oxidative properties. The phenolic acid
      moieties might be the functional sites. This arabinogalactan can form a complex
      with bovine serum albumin having binding constant K=6.48 * 10(6)/M. Thus, this
      study is an important step forward to investigate the involvement of
      arabinogalactan in processes including interaction with biologically important
      transport proteins.

PMID- 24299783
TI  - Lepidium perfoliatum seed gum: a new source of carbohydrate to make a
      biodegradable film.
AB  - Microstructural, physical, mechanical and thermal properties of a novel
      biodegradable film based on Lepidium perfoliatum seed gum (LPSG) were
      investigated. LPSG films were successfully prepared by incorporation of four
      levels of glycerol (40%, 50%, 60% and 70%, w/w). As expected, increasing glycerol
      concentration from 40 to 70% (w/w), increased water vapor permeability (WVP),
      elongation at break (EB%), moisture content, moisture adsorption and water
      solubility of LPSG films; whilst, elastic modulus (EM), contact angle, melting
      point (Tm), enthalpy of melting (DeltaHm) and glass transition point (Tg)
      decreased significantly. LPSG films became slightly greenish and yellowish in
      color but still transparent in appearance. The images taken from electron
      scanning microscopy indicated uniform surface, compact sheets with no holes or
      fracture. This study demonstrates that LPSG based films with desired properties
      can be obtained by adjusting glycerol content. 

PMID- 24299784
TI  - Enzymatic preparation of kappa-carrageenan oligosaccharides and their anti
      angiogenic activity.
AB  - The mixture of kappa-neocarrabiose-sulfate, kappa-neocarrahexaose-sulfate and
      kappa-neocarraoctaose-sulfate were prepared from kappa-carrageenan with enzyme.
      The anti-tumor and anti-angiogenic activity of obtained kappa-carrageenan
      oligosaccharides (KOS), were explored. The results showed that KOS could inhibit
      the proliferation, migration and tube formation of ECV304 cells, and could
      inhibit the growth of new vessels in CAM model. KOS displayed strong anti-tumor
      activity in both S180 and MCF-7 xenograft models. Only human CD105 was detected
      in MCF-7 xenograft tumor, moreover KOS could decrease the growing of new blood
      vessels derived from tumor cell. Real-time PCR results showed that KOS could
      suppress the mRNA expression of human VEGF, bFGF, bFGFR and CD105 in MCF-7
      xenograft tumor. All these results indicated that KOS has anti-tumor and anti
      angiogenic activity in vivo and in vitro. Especially K has the potency to inhibit
      the differentiation of tumor cell to blood vessel endothelial cell. 

PMID- 24299785
TI  - Inulin-type fructans: a review on different aspects of biochemical and
      pharmaceutical technology.
AB  - Inulin is a natural storage polysaccharide with a large variety of food and
      pharmaceutical applications. It is widely distributed in plants, being present as
      storage carbohydrate in more than 30,000 vegetable products. Due to their wide
      distribution in nature and significant role in industry, the extraction,
      isolation and characterization of inulin-type fructans are gaining attention in
      recent years. Inulin sources have recently received increasing interest as they
      are a renewable raw material for the production of bioethanol, fructose syrup,
      single-cell protein and single cell oil, obtainment of fructooligosaccharides and
      other useful products. This review focuses on the state-of-the-art of biochemical
      and pharmaceutical technology of inulin-type fructans. 

PMID- 24299786
TI  - Pulsed counter-current ultrasound-assisted extraction and characterization of
      polysaccharides from Boletus edulis.
AB  - Four methods for extracting polysaccharides from Boletus edulis, namely, hot
      water extraction, ultrasonic clearer extraction, static probe ultrasonic
      extraction, and pulsed counter-current probe ultrasonic extraction (CCPUE), were
      studied. Results showed that CCPUE has the highest extraction efficiency among
      the methods studied. Under optimal CCPUE conditions, a B. edulis polysaccharide
      (BEP) yield of 8.21% was obtained. Three purified fractions, BEP-I, BEP-II, and
      BEP-III, were obtained through sequential purification by DEAE-52 and Sephadex G
      75 chromatography. The average molecular weights of BEP-I, BEP-II, and BEP-III
      were 10,278, 23,761, and 42,736 Da, respectively. The polysaccharides were mainly
      composed of xylose, mannose, galactose, and glucose; of these, mannose contents
      were the highest. The antioxidant activities of the BEPs were further
      investigated by measurement of their ability to scavenge DPPH and hydroxyl
      radicals as well as their reducing power. The results indicated that the BEPs
      have good antioxidant activity.

PMID- 24299787
TI  - Polysaccharides from Panax japonicus C.A. Meyer and their antioxidant activities.
AB  - Polysaccharides named as PP1, PP2, PP3, PP4 and PP5 were extracted and isolated
      from the rhizomes of Panax japonicus C.A. Meyer, a well-known Chinese traditional
      medicine, by controlling the final concentration of solution to precipitate the
      polysaccharides. The molecular weight of polysaccharides was determined by HGPLC
      chromatography system. The monosaccharide composition was analyzed by Gas
      chromatography on an Agilent 6890A instrument using a DB-35MS column and flame
      ionization detector. All of the polysaccharides were heteropolysaccharides and
      consisted of arabinose, glucose and galactose. The content of arabinose increased
      with the increasing of ethanol concentration and PP5 had the most arabinose
      content in these samples. IR spectra indicated obvious characteristic peaks of
      polysaccharide, the presence of uronic acids. Their antioxidant activities were
      evaluated by various established in vitro systems, including scavenging activity
      of superoxide anion, hydroxyl radical, ABTS and DPPH radicals. Both samples
      showed inhibitory effects on superoxide, hydroxyl, ABTS and DPPH radical. And PP5
      shows more clearly and relatively stronger capacity than other polysaccharides on
      the protective effect of DNA damage. 

PMID- 24299788
TI  - Porous graphene oxide/carboxymethyl cellulose monoliths, with high metal ion
      adsorption.
AB  - Orderly porous graphene oxide/carboxymethyl cellulose (GO/CMC) monoliths were
      prepared by a unidirectional freeze-drying method. The porous monoliths were
      characterized by Fourier transform infrared spectra, X-ray diffraction and
      scanning electron microscopy. Their properties including compressive strength and
      moisture adsorption were measured. The incorporation of GO changed the porous
      structure of the GO/CMC monoliths and significantly increased their compressive
      strength. The porous GO/CMC monoliths exhibited a strong ability to adsorb metal
      ions, and the Ni(2+) ions adsorbed on GO/CMC monolith were reduced by NaBH4 to
      obtain Ni GO/CMC monolith which could be used as catalyst in the reduction of 4
      nitrophenol to 4-aminophenol. Since CMC is biodegradable and non-toxic, the
      porous GO/CMC monoliths are potential environmental adsorbents. 

PMID- 24299789
TI  - Enhanced water vapour barrier and grease resistance of paper bilayer-coated with
      chitosan and beeswax.
AB  - In order to overcome the deficiencies of single layer coating, bilayer coated
      papers were prepared by two separate coating procedures using various
      combinations of proteins or polysaccharides with beeswax. Among those
      combinations, chitosan-beeswax bilayer coated paper showed the best water vapour
      barrier property. It was observed that as the concentration of chitosan solution
      increased from 1.0 to 3.0 wt%, its water vapour transport rate (WVTR) decreased
      from 171.6 to 52.8 g/m(2)/d but using reduced beeswax coating weight (from 10.1
      to 4.9 g/m(2)). It also displayed an enhanced performance of grease resistance.
      Scanning electron microscopy (SEM) showed that beeswax layer was fitted to
      chitosan layer so closely that these two layers are indistinguishable. Confocal
      laser scanning microscope (CLSM) further confirmed the existence of an integrated
      chitosan film between beeswax layer and paper base and a thin composite layer
      consisting of chitosan and beeswax.

PMID- 24299790
TI  - Formation of crystalline complexes between amylomaize dextrin and ceramide.
AB  - Complexes between amylomaize dextrin (average DP 311) and ceramide were prepared
      by using two different blending systems: an aqueous batch system containing
      ethanol and a two-phase system of isopropyl ether and water. The organic solvents
      and complex formation temperature (50-90 degrees C) were important in determining
      the level of complex formation and its crystalline structure. Under X-ray
      diffraction analysis, the solvents as well as ceramide could form complexes with
      dextrin as weak V6I type crystals. However, the crystallinity of complexes was
      much higher in the presence of ceramide, which would enhance complex formation by
      forming ternary co-inclusion complexes of dextrin-solvent-ceramide. Compared to
      the two-phase system, the batch system yielded much higher crystallinity of
      complexes. With a minor use of ethanol (0.5 mL) in the batch system, aqueous
      blending of dextrin and ceramide at 50 degrees C for 2 days followed by a storage
      at 25 degrees C for 1 day produced well-defined V6I crystal particles as
      precipitates. The isolated particles had rectangular shapes with a size of 1 MUm
      or less, and contained about half of the ceramide initially added. The ceramide
      dextrin complex exhibited enhanced water dispersibility, up to 45% based on the
      ceramide content in complex.

PMID- 24299791
TI  - Effect of pH on the physico-mechanical properties and miscibility of methyl
      cellulose/poly(acrylic acid) blends.
AB  - The miscibility behavior and physico-mechanical properties between methyl
      cellulose (MC) of different molecular weights (4 * 10(4) and 8.3 * 10(4)g/mol)
      and poly(acrylic acid) (PAA) were studied by viscometry, differential scanning
      calorimetry (DSC), thermal gravimetric analysis (TGA), tensile strength and
      scanning electron microscopy (SEM) using water as a solvent. Various formulations
      were designed to investigate the effects of process variables such as pH on the
      physico-mechanical and miscibility properties of MC/PAA blends. The rheological
      features for the obtained blends are strongly dependent on the molecular weight
      of the MC used and pH. The viscosity measurements showed that all blends have non
      Newtonian shear thinning (pseudoplastic) behavior. These blends have a single
      glass transition indicating that these blends are able to form a miscible phase
      due to the formation of hydrogen bonds between the hydroxyl group of MC and the
      carboxyl group of PAA. The MC/PAA blends exhibit good mechanical properties,
      thermal stability, characteristics of a MC-PAA polymer network. SEM of the blends
      showed no phase separation, when compared with the pure MC and PAA.

PMID- 24299792
TI  - Extraction, isolation and characterisation of phytoglycogen from su-1 maize
      leaves and grain.
AB  - Phytoglycogen is a highly branched soluble alpha-glucan found in plants,
      particularly those with decreased activity of isoamylase-type starch debranching
      enzyme, such as sugary-1 (su-1) maize. An improved technique has been designed to
      extract and isolate phytoglycogen from the grain and leaves of su-1 maize with
      minimal degradation for structural characterisation. The structures of extracted
      phytoglycogen samples were analysed using size-exclusion chromatography (SEC,
      also termed GPC) and transmission electron microscopy (TEM) and compared with the
      structure of pig liver glycogen. The SEC weight molecular size distributions
      indicate that the extraction procedure with protease is most effective in
      obtaining pure phytoglycogen from grain, whereas that without protease at cold
      temperature followed by purification using a sucrose gradient is more effective
      for leaf material. The extracted and purified phytoglycogen samples from both
      grain and leaf contain wide distributions of molecular sizes (analysed by SEC and
      TEM), with the smallest being "individual" beta particles, which collectively
      form larger alpha particles; the latter are dominant in the phytoglycogen samples
      examined here. The results show that phytoglycogen is similar to liver glycogen
      in both the range of molecular size distribution and in the presence of alpha
      particles. 

PMID- 24299793
TI  - Cellulase-assisted extraction of polysaccharides from Cucurbita moschata and
      their antibacterial activity.
AB  - In this study, cellulase-assisted extraction of water soluble polysaccharides
      from pumpkin (Cucurbita moschata) and their antibacterial activity were
      investigated. The polysaccharides yield was monitored during the extraction
      process. The optimum extraction conditions were determined as follows: time, 40
      min; temperature, 55 degrees C; pH, 4.5; and cellulase amount, 4,000 U/g. The
      extracts were centrifuged, filtered, proteins removed by Sevag method,
      concentrated to approximately 15% (w/v), precipitated with 5 volumes of absolute
      ethanol, freeze-dried, and pulverized to yield a water soluble powder of pumpkin
      polysaccharides (PP). The sugar content of the product was 68.3%, and the yield
      was 17.34% (w/w), respectively. The PP had high antibacterial activity against
      Bacillus subtilis, Staphylococcus aureus, and Escherichia coli at the
      concentration of 100 mg/mL.

PMID- 24299794
TI  - Effect of uracil on pullulan production by Aureobasidium pullulans CGMCC1234.
AB  - Effect of uracil on the pullulan production, biomass and uridine phosphorylase
      (UPase) activity was studied in this research. Uracil was found to enhance
      pullulan accumulation and the addition time of uracil was crucial to pullulan
      production. Pullulan yield of 49.07 g/L was achieved by adding 5mM uracil at 48
      h, by comparison to 37.72 g/L obtained with the control. UPase activity could not
      be detected at early growth stage of Aureobasidium pullulans, but stimulated by
      added uracil at logarithmic phase and stationary phase. The time course study on
      the fermentation of pullulan demonstrates that pullulan production was not
      closely associated with biomass accumulation. Results indicate that the increased
      pullulan yield brought by uracil was correlated with UPase activity.

PMID- 24299795
TI  - Structure of the oligosaccharides isolated from Prosopis juliflora (Sw.) DC. seed
      polysaccharide.
AB  - A water soluble polysaccharide isolated from Prosopis juliflora seed was purified
      and major homogenous fraction obtained by GPC. Complete hydrolysis of the
      polysaccharide followed by paper chromatography and GLC analysis indicated the
      presence of d-galactose and d-mannose in the ratio 1:1.10, respectively. Partial
      hydrolysis of the polysaccharide furnished one hepta-(I), one octa-(II) and nona
      (III) saccharides. Hydrolysis of oligosaccharide I, II and III followed by GLC
      analysis furnished d-galactose and d-mannose in the ratio 3:4, 3:5 and 5:4,
      respectively. Methylation analysis, periodate oxidation and (1)H NMR spectral
      studies of oligosaccharides indicated the presence of (1->4) mannose units linked
      to (1->6) galactose units.

PMID- 24299796
TI  - Acylation of cellulose in a novel solvent system: solution of
      dibenzyldimethylammonium fluoride in DMSO.
AB  - A novel electrolyte, dibenzyldimethylammonium fluoride has been obtained
      essentially anhydrous (BMAF-0.1H2O) by a simple route. Its thermal stability,
      relative to tetra(1-butyl)ammonium fluoride trihydrate (TBAF3H2O) has been
      demonstrated by thermogravimetric analysis. DMSO solution of (BMAF-0.1H2O)
      dissolves microcrystalline- and fibrous celluloses; the dissolved biopolymers
      have been acylated by ethanoic-, butanoic-, and hexanoic anhydride. The degrees
      of substitution of the esters are higher than with TBAF3H2O/DMSO. The reasons are
      discussed in terms of differences in electrolyte structure and contents of water
      of hydration, whose presence leads to side reactions and decreases of the
      basicity of (F(-)). This conclusion is corroborated by molecular dynamics
      simulations of the interactions of glucose dodecamer/R4NF-hydrate/DMSO. These
      show that the interactions oligomer-F(-)-water is operative only for
      TBAF3H2O/DMSO. The efficiency of BMAF-0.1H2O/DMSO is explained based on better
      accessibility of the biopolymer due to efficient hydrogen-bonding between its
      hydroxyl groups and the essentially desolvated (F(-)). 

PMID- 24299797
TI  - Effect of biopolishing and UV absorber treatment on the UV protection properties
      of cotton knitted fabrics.
AB  - Cotton knitted fabrics were manufactured with gauge number 20 G by circular
      knitting machine with conventional ring spun yarn and torque-free ring spun yarn.
      Torque-free ring spinning is a new spinning technology that produces yarns with
      low twist and balanced torque. This study examined whether the impact of
      biopolishing and UV absorber treatment on UV protection properties on cotton
      knitted fabric made of torque-free ring spun yarn is different. Biopolishing
      agent and UV absorber were used to treat the cotton knitted fabrics after
      scouring and bleaching. The UV protection properties were measured in terms of UV
      protection factor (UPF) and UV ray transmittance. Experimental results revealed
      that knitted fabric made from torque-free ring spun has better UPF than knitted
      fabric made from conventional ring spun yarn in untreated and biopolished states.
      However, knitted fabric made from conventional ring spun yarn has better UPF than
      knitted fabric made from torque-free ring spun after UV absorber treatment and
      combined UV absorber and biopolishing treatment.

PMID- 24299798
TI  - Polysaccharides with immunomodulating properties from the bark of Parkia
      biglobosa.
AB  - The bark of Parkia biglobosa is used in traditional medicine to cure a wide range
      of illnesses. Polysaccharides were extracted from the bark with 50% ethanol
      water, 50 degrees C and 100 degrees C water, and seven active fractions obtained
      by anion exchange chromatography and gel filtration. The complement fixation and
      macrophage stimulating activities of the different fractions were determined. The
      acidic fractions PBEII-I and PBEII-IV were the most active in the complement
      fixation assay, but the other fractions were also potent compared to the positive
      control BPII from Biophytum petersianum. Fractions PBEII-I and PBEII-IV were also
      the most potent fractions in stimulating macrophages to release nitric oxide.
      Structural studies showed that PBEII-I and PBEII-IV were pectic type
      polysaccharides, containing arabinogalactan type II structures. The observed
      differences in biological activities among the seven purified polysaccharide sub
      fractions are probably due to differences in monosaccharide compositions, linkage
      types and molecular sizes. 

PMID- 24299799
TI  - Evaluation of the effects of chitin nanofibrils on skin function using skin
      models.
AB  - Chitins are highly crystalline structures that are predominantly found in
      crustacean shells. Alpha-chitin is composed of microfibers, which are made up of
      nanofibrils that are 2-5 nm in diameter and 30 nm in length and embedded in a
      protein matrix. Crystalline nanofibrils can also be prepared by acid treatment.
      We verified the effect of chitin nanofibrils (NF) and nanocrystals (NC) on skin
      using a three-dimensional skin culture model and Franz cells. The application of
      NF and NC to skin improved the epithelial granular layer and increased granular
      density. Furthermore, NF and NC application to the skin resulted in a lower
      production of TGF-beta compared to that of the control group. NF and NC might
      have protective effects to skin. Therefore, their potential use as components of
      skin-protective formulations merits consideration.

PMID- 24299800
TI  - Surface grafting of cellulose nanocrystals with poly(3-hydroxybutyrate-co-3
      hydroxyvalerate).
AB  - Chemically modified cellulose nanocrystals (CNCs) were synthesized by grafting
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) onto CNCs via homogeneous
      acylation reaction between N,N-dimethyl formamide (DMF) by using toluene
      diisocyanate (TDI) as coupling agent and dibutyltin dilaurate as catalyst. The
      resulting copolymers were studied by using (1)HNMR, FT-IR, WAXD, DSC, TGA and
      contact angle measurements. Results showed that the copolymers kept their initial
      morphological integrity. Moreover, it is found that with the increase of the
      TDI/PHBV fractions, two transition exhibitions occurred in their thermal and
      hydrophobic properties, which could be modulated through controlling the lengths
      and grafting densities of PHBV side chains. Compared with those of neat PHBV, the
      crystallization of PHCN7 became easy while the crystallinity slightly decreased
      to 55.5%, the maximum decomposition temperature increased by 48.5 degrees C,
      meanwhile the contact angle increased to 58 degrees  as compared to neat CNCs (30
      degrees ). 

PMID- 24299801
TI  - Separation of water-soluble polysaccharides from Cyclocarya paliurus by
      ultrafiltration process.
AB  - In this study, ultrafiltration membrane process was employed to separate
      polysaccharides from Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) to
      simulate industrial production. Meanwhile, the molecular weight distribution of
      C. paliurus polysaccharides was investigated by gel permeation chromatography.
      Four fractions were obtained and named as CPPS-A, CPPS-B, CPPS-C and CPPS-D,
      respectively. CPPS-A and CPPS-B contained approximately 69.5% and 12.7% of
      polysaccharides, whose molecular weight were in the range of 100-300 kDa and 120
      kDa, respectively. CPPS-C was comprised of two polysaccharides with average
      molecular weight of 40 kDa and 15 kDa. Results showed that ultrafiltration
      resulted in the removal of parts of small molecule weight polysaccharides, the
      increase of proportion of high molecule weight ones and the obvious improvement
      of quality of products. Compared with ethanol precipitation and gel permeation
      chromatography techniques, ultrafiltration showed many advantages, and also
      provided theoretical support for industrial manufacturing of C. paliurus
      polysaccharides in separation.

PMID- 24299802
TI  - Controllable production of low molecular weight heparins by combinations of
      heparinase I/II/III.
AB  - Enzymatic depolymerization of heparin by heparinases is promising for production
      of low molecular weight heparins (LMWHs) as anticoagulants, due to its mild
      reaction conditions and high selectivity. Here, different heparinase combinations
      were used to depolymerize heparin. Heparinase I and heparinase II can
      depolymerize heparin more efficiently than heparinase III, respectively, but
      heparinase III was the best able to protect the anticoagulant activities of
      LMWHs. Heparinase III and heparinase I/II combinations were able to efficiently
      depolymerize heparin to LMWHs with higher anticoagulant activity than the LMWHs
      produced by the respective heparinase I and heparinase II. HepIII and HepI is the
      best combination for maintaining high anti-IIa activity (75.7 +/- 4.21 IU/mg) at
      the same Mw value. Furthermore, considering both the changes in molecular weight
      and anticoagulant activity, the action patterns of heparinase I and heparinase II
      were found not to follow the exolytic and processive depolymerizing mechanism
      from the reducing end of heparin.

PMID- 24299803
TI  - Effects of hydrothermal pretreatment on subsequent octenylsuccinic anhydride
      (OSA) modification of cornstarch.
AB  - Cornstarch granules were hydrothermally pretreated and then esterified with
      octenylsuccinic anhydride (OSA). The physicochemical properties of cornstarch and
      hydrothermally pretreated OS-starch (H-OS-starch) were investigated. Results
      showed that hydrothermal pretreatments significantly increased the degree of
      substitution (DS) and reaction efficiency (RE) of H-OS-starch compared with the
      control. The higher the pretreatment temperature was, the more the OSA could go
      deep into the internal starch granules. The optimal pretreatment temperature for
      the OSA modification was 60 degrees C. In addition, the OS groups appeared to be
      distributed throughout the OS-starch granules, especially on the surface, as
      shown by confocal laser scanning microscopy (CLSM). H-OS-starch had a slightly
      higher peak viscosity (Pv) and break down (BD) values, but lower pasting
      temperature (Tp) compared with the control OS-starch. 

PMID- 24299804
TI  - Dissolution and rheological behavior of deacetylated konjac glucomannan in urea
      aqueous solution.
AB  - Deacetylation adversely affected the solubility of konjac glucomannan (KGM).
      Herein the dissolution behavior of deacetylated KGM (da-KGM) was studied in 10
      wt% urea solution at various temperatures. KGM with different degrees of
      deacetylation (DD) could be well dissolved at -4 degrees C. Low temperature was
      conducive to the dissolution of da-KGM. The result from steady shear showed that
      the zero-shear viscosity decreased with the increase of DD, with the rheological
      model being conformed to the Cross equation. Dynamic viscoelastic properties
      indicated the da-KGM gel formed more easily with increasing concentration, or
      decreasing temperature and DD. Temperature sweep revealed that gel process could
      be divided into two stages. The first stage was that both storage modulus (G')
      and loss modulus (G") fell until the temperature reached 90 degrees C. The second
      stage was that G' and G" increased abruptly, presenting the transition from sol
      to gel.

PMID- 24299805
TI  - Effect of HPMC concentration on beta-cyclodextrin solubilization of norfloxacin.
AB  - The effect of hydroxypropyl methylcellulose (HPMC) concentration on beta
      cyclodextrin (beta-CD) solubilization of norfloxacin was examined. The solubility
      and dissolution of norfloxacin/beta-CD and norfloxacin/beta-CD/HPMC inclusion
      complexes were studied. The presence of beta-CD increased significantly the
      solubility and dissolution of norfloxacin. The addition of HPMC until 5% (w/w)
      improved the solubilization of norfloxacin but further addition above 5% (w/w),
      decreased norfloxacin solubilization. Fourier transformed Infra-red (FTIR) showed
      that norfloxacin was successfully included into beta-CD. Differential scanning
      calorimetry (DSC) showed that the norfloxacin endothermic peak shifted to a lower
      temperature with reduced intensity indicating the formation of inclusion complex.
      The addition of HPMC reduced further the intensity of norfloxacin endothermic
      peak. Most of the sharp and intense peaks of norfloxacin disappeared with the
      addition of HPMC. In conclusion, the concentration of hydrophilic polymer used to
      enhance beta-CD solubilization of poorly soluble drugs is very critical. 

PMID- 24299806
TI  - Cloning and expression of the cold-adapted endo-1,4-beta-glucanase gene from
      Eisenia fetida.
AB  - Biofuel production from plant-derived lignocellulosic material using fungal
      cellulases is facing cost-effective challenges related to high temperature
      requirements. The present study identified a cold-adapted cellulase named endo
      1,4-beta-glucanase (EF-EG2) from the earthworm Eisenia fetida. The gene was
      cloned in the cold-shock expression vector (pCold I) and functionally expressed
      in Escherichia coli ArcticExpress RT (DE3). The gene consists of 1,368 bp
      encoding 456 amino acid residues. The amino acid sequence shares sequence
      homology with the endo-1,4-beta-glucanases of Eisenia andrei (98%), Pheretima
      hilgendorfi (79%), Perineresis brevicirris (63%), and Strongylocentrotus nudus
      (58%), which all belong to glycoside hydrolase family 9. Purified recombinant EF
      EG2 hydrolyzed soluble cellulose (carboxymethyl cellulose), but not insoluble
      (powdered cellulose) or crystalline (Avicel) cellulose substrates. Thin-layer
      chromatography analysis of the reaction products from 1,4-beta-linked
      oligosaccharides of various lengths revealed a cleavage mechanism consistent with
      endoglucanases (not exoglucanases). The enzyme exhibited significant activity at
      10 degrees C (38% of the activity at optimal 40 degrees C) and was stable at pH
      5.0-9.0, with an optimum pH of 5.5. This new cold-adapted cellulase could
      potentially improve the cost effectiveness of biofuel production.

PMID- 24299807
TI  - Synthesis of chitosan molecularly imprinted polymers for solid-phase extraction
      of methandrostenolone.
AB  - Chitosan molecularly imprinted polymers (CHI-MIPs) for selective extraction of
      methandrostenolone (MA) was synthesized by cross-linking of chitosan with
      epichlorohydrin in the presence of MA as the template molecule. Systematic
      investigations of the influences of template, functional polymer, cross-linker as
      well as porogen concentrations on the rebinding capacity of CHI-MIPs were carried
      out. Adsorption and kinetic binding experiments indicated that the synthesized
      CHI-MIPs had high adsorption and excellent affinity to MA. Solid-phase extraction
      (SPE) using the prepared CHI-MIPs as adsorbent was then investigated, and the
      optimum loading and eluting conditions for SPE of the MA were established. The
      optimized SPE procedure was used to extract the MA from several spiked samples
      and a good sample clean-up was obtained with the average recoveries ranged from
      95.97 to 101.79%. 

PMID- 24299808
TI  - Gum arabic/starch/maltodextrin/inulin as wall materials on the microencapsulation
      of rosemary essential oil.
AB  - The effects of the partial or total replacement of gum arabic by modified starch,
      maltodextrin and inulin on the characteristics of rosemary essential oil
      microencapsulated by spray drying were evaluated in this study. The lowest level
      of water absorption under conditions of high relative humidity was observed in
      treatments containing inulin. The wettability property of the powders was
      improved by the addition of inulin. The total replacement of gum arabic by
      modified starch or a mixture of modified starch and maltodextrin (1:1, m/m) did
      not significantly affect the efficiency of encapsulation, although higher Tg
      values were exhibited by microcapsules prepared using pure gum arabic or gum
      arabic and inulin. 1,8-cineol, camphor and alpha-pinene were the main components
      identified by gas chromatography in the oils extracted from the microcapsules.
      The particles had smoother surfaces and more folds when gum arabic or inulin was
      present. Larger particles were observed in the powders prepared with pure gum
      arabic or modified starch. 

PMID- 24299809
TI  - Protective effect of Millettia pulchra polysaccharide on cognitive impairment
      induced by D-galactose in mice.
AB  - A polysaccharide (PMP) was isolated from Millettia pulchra and purified by DEAE
      cellulose and Sephadex G-75 chromatography. The results showed that PMP was
      composed of d-glucose and d-arabinose in a molar ratio of 90.79% and 9.21%, with
      an average molecular weight of about 14,301 Da. Furthermore, the effect of PMP on
      cognitive impairment induced by d-galactose in mice was evaluated. Treatment with
      PMP significantly reversed d-galactose-induced learning and memory impairments,
      as measured by behavioral tests. One of the potential mechanisms of this action
      was to reduce oxidative stress and suppress inflammatory responses. Furthermore,
      our results also showed that PMP markedly reduced the content and deposition of
      beta-amyloid peptide, improved the dysfunction of synaptic plasticity, increased
      the levels of acetylcholine, but decreased cholinesterase activity. These results
      suggest that PMP exerts an effective protection against d-galactose-induced
      cognitive impairment, and PMP may be a major bioactive ingredient in M. pulchra.

PMID- 24299810
TI  - Understanding complex coacervation in serum albumin and pectin mixtures using a
      combination of the Boltzmann equation and Monte Carlo simulation.
AB  - A combination of turbidimetric titration, a sigmoidal Boltzmann equation approach
      and Monte Carlo simulation has been used to study the complex coacervation in
      serum albumin and pectin mixtures. The effects of the mass ratio of protein to
      polysaccharide on the critical pH values, the probability of complex coacervation
      and the electrostatic interaction from charge patches in serum albumin were
      investigated. Turbidimetric titration results showed an optimum pH for complex
      coacervation (pHm), which corresponded to the maximum turbidity in the
      protein/polysaccharide mixture. The pHm monotonically decreased as the ratio
      decreased, and could be fitted using the sigmoidal Boltzmann equation. It
      suggests that pHm could be a good ordering parameter to characterize the phase
      behavior associated with protein/polysaccharide complex coacervation. Qualitative
      understanding of pHm by taking into account the minimization of electrostatic
      interaction, as well as quantitative matching of pHm according to the concept of
      charge neutralization were both achieved. Our results suggest that the serum
      albumin/pectin complexes were ultimately neutralized by the partial charges
      originated from the titratable residues in protein and polysaccharide chains at
      pHm. The Monte Carlo simulation provided consistent phase boundaries for complex
      coacervation in the same system, and the intermolecular association strength was
      determined to be several kBT below the given ionic strength. The strongest
      binding site in the protein is convergent to the largest positive charge patch if
      pure electrostatic interaction was considered. Further inclusion of contribution
      from excluded volume resulted in the binding site distribution over five
      different positive charge patches at different protein/polysaccharide ratios and
      pH values. 

PMID- 24299811
TI  - Weissella confusa Cab3 dextransucrase: properties and in vitro synthesis of
      dextran and glucooligosaccharides.
AB  - Food-derived Weissella spp. have gained attention during recent years as
      efficient dextran producers. Weissella confusa Cab3 dextransucrase (WcCab3-DSR)
      was isolated applying PEG fractionation and used for in vitro synthesis of
      dextran and glucooligosaccharides. WcCab3-DSR had a molar mass of 178 kDa and was
      activated by Co(2+) and Ca(2+) ions. Glycerol and Tween 80 enhanced enzyme
      stability, and its half-life at 30 degrees C increased from 10h to 74 h and 59 h,
      respectively. The (1)H and (13)C NMR spectral analysis of the produced dextran
      confirmed the presence of main chain alpha-(1->6) linkages with only 3.0% of
      alpha-(1->3) branching, of which some were elongated. An HPSEC analysis in DMSO
      revealed a high molecular weight of 1.8 * 10(7)g/mol. Glucooligosaccarides
      produced through the acceptor reaction with maltose, were analyzed with HPAEC-PAD
      and ESI-MS/MS. They were a homologous series of isomaltooligosaccharides with
      reducing end maltose units. To the best of our knowledge, this is a first report
      on native W. confusa dextransucrase.

PMID- 24299812
TI  - Montmorillonite-levan nanocomposites with improved thermal and mechanical
      properties.
AB  - This work reports on the structure and properties of novel nanocomposites
      composed of exfoliated montmorillonite clay blended with levan, a polysaccharide
      produced by Bacillus sp. Dry levan is very brittle, making it difficult to obtain
      stand-alone films. MMT-levan composites were prepared by solution blending in
      water, coating on plastic surfaces, partial drying at 50 degrees C, and
      conditioning in air at 50-60% relative humidity. This process results in
      freestanding, transparent, and flexible films of pure levan and MMT-levan
      composites plasticized by 10-15 wt% water. XRD patterns from levan-MMT composites
      indicate an MMT interlayer spacing 0.62 nm greater than that of the starting MMT,
      suggesting re-stacking of MMT platelets coated by adsorbed, uncoiled levan
      molecules. FTIR results suggest that levan adheres to MMT via water-mediated
      hydrogen bonding between the levan's hydroxyl groups and MMT surface oxygens. MMT
      levan composites have improved thermal stability and a well-defined glass
      transition temperature that increases with MMT loading. The tensile moduli of
      levan-MMT composites increase by as much as 480% relative to pure levan. The XRD
      and mechanical property results suggest that MMT reinforces levan through a
      filler network structure composed of MMT platelets bridged by adsorbed levan
      molecules, enhanced when the MMT loading becomes high enough (5-10wt% MMT) to
      induce an isotropic-nematic transition in MMT platelet orientation.

PMID- 24299813
TI  - Peach gum for efficient removal of methylene blue and methyl violet dyes from
      aqueous solution.
AB  - This study investigated the potential use of natural peach gum (PG) as
      alternative adsorbent for the removal of dyes from aqueous solutions. The PG
      showed high adsorption capacities and selectivity for cationic dyes (e.g.,
      methylene blue (MB) and methyl violet (MV)) in the pH range 6-10. 98% of MB and
      MV could be adsorbed within 5 min, and both of the adsorptions reached
      equilibrium within 30 min. The dye uptake process followed the pseudo-second
      order kinetic model. The intraparticle diffusion was not the sole rate
      controlling step. Equilibrium adsorption isotherm data indicated a good fit to
      the Langmuir isotherm model. Regeneration study revealed that PG could be well
      regenerated in acid solution. The recovered PG still exhibited high adsorption
      capacity even after five cycles of desorption-adsorption. On the basis of its
      excellent adsorption performance and facile availability, PG can be employed as
      an efficient low cost adsorbent for environmental cleanup.

PMID- 24299814
TI  - Characterization of kappa-carrageenan films incorporated plant essential oils
      with improved antimicrobial activity.
AB  - Antioxidant and antimicrobial kappa-carrageenan-based films containing different
      concentrations of Zataria multiflora Boiss (ZEO) and Mentha pulegium (MEO)
      essential oils were developed, and their water vapor permeability (WVP), optical,
      microstructure, antioxidant and antimicrobial properties were characterized. ZEO
      and MEO decreased the WVP of the emulsified films; for example, 3% ZEO reduced
      WVP by around 80%. Increasing the content of ZEO or MEO from 1% to 3% (v/v)
      increased values for elongation at break from 37.43% to 44.74% and from 36.09% to
      41.25% respectively. Carrageenan-composite films were less resistant to breakage,
      more flexible and more opaque with lower gloss. These properties were related to
      the film's microstructure as analyzed by atomic force microscopy and scanning
      electron microscopy. ZEO affected the antioxidant properties of the films more
      markedly than MEO, e.g., ZEO containing films showed DPPH radical scavenging of
      80.6% which were two-fold higher than those having MEO. The films' antimicrobial
      activities were increased by incorporating essential oils, particularly ZEO,
      which were more effective against the bacteria in the direct-contact method than
      a vapor phase. S. aureus was found to be the most sensitive bacterium to either
      ZEO or MEO, followed by B. cereus and E. coli. A highest inhibition zone of
      544.05 mm(2) was observed for S. aureus around the films incorporated with 3%
      (v/v) ZEO. The total inhibitory zone of 3% (v/v) MEO formulated films was 20.43
      for S. typhimurium and 10.15 mm(2) for P. aeruginosa. These results revealed that
      ZEO and MEO have good potential to be incorporated into kappa-carrageenan to make
      antimicrobial and antioxidant edible films for food applications.

PMID- 24299815
TI  - Syntheses of glucomannan esters and their thermal and mechanical properties.
AB  - Fully substituted glucomannan (GM) acylates with acyl carbon numbers (n) of 2, 3,
      4, 5, 6, 8, 10, and 12 were prepared from konjac GM (KGM) in carboxylic
      acid/trifluoroacetic anhydride (TFAA). GM acetate acylates (n=3, 4, 5, 8, 12, 16,
      and 18) were prepared from KGM in acetic acid/carboxylic acid/TFAA. Differential
      scanning calorimetry (DSC) and X-ray diffraction revealed that the GM esters did
      not exhibit melting peaks and reflections derived from crystal, indicating they
      were amorphous. The glass-transition temperatures (Tgs) of the GM esters tended
      to decrease with increasing acyl carbon number, ranging from 174 degrees C for GM
      acetate (GMAc) to 64 degrees C for GM laurate (GMLa). Colorless and transparent
      GM ester films were obtained by solvent casting and thermo-pressing. The
      mechanical properties of the GM ester films were controlled by the acyl group
      structure. 

PMID- 24299816
TI  - Encapsulation altered starch digestion: toward developing starch-based delivery
      systems.
AB  - Starch is an abundant biomaterial that forms a vital energy source for humans.
      Altering its digestion, e.g. increasing the proportions of slowly digestible
      starch (SDS) and resistant starch (RS), would revolutionize starch utility in
      addressing a number of health issues related to glucose absorption, glycemic
      index and colon health. The research reported in this article is based on my
      hypothesis that water channels present in the B-type starch crystalline matrix,
      particularly in tuber starches, can embed guest molecules such as nutraceuticals,
      drugs, flavor compounds and vitamins leading to altered starch digestion. Toward
      this goal, potato starch has been chosen as the model tuber starch, and
      ibuprofen, benzocaine, sulfapyridine, curcumin, thymol and ascorbic acid as model
      guest molecules. X-ray powder diffraction and FT-IR analyses clearly suggest the
      incorporation of guest molecules in the water channels of potato starch.
      Furthermore, the in vitro digestion profiles of complexes are intriguing with
      major variations occurring after 60 min of starch digestion and finally at 120
      min. These changes are concomitantly reflected in the SDS and RS amounts, with
      about 24% decrease in SDS for benzocaine complex and 6% increase in RS for
      ibuprofen complex, attesting the ability of guest molecule encapsulation in
      modulating the digestion properties of potato starch. Overall, this research
      provides an elegant opportunity for the design and development of novel starch
      based stable carriers that not only bestow tailored glucose release rates but
      could also transport health promoting and disease preventing compounds.

PMID- 24299817
TI  - Optimization of enzyme-assisted extraction and characterization of
      polysaccharides from Hericium erinaceus.
AB  - The enzyme-assisted extraction (EAE) of polysaccharides from the fruits of
      Hericium erinaceus was studied. In this study, response surface methodology and
      the Box-Behnken design based on single-factor and orthogonal experiments were
      applied to optimize the EAE conditions. The optimal extraction conditions were as
      follows: a pH of 5.71, a temperature of 52.03 degrees C and a time of 33.79 min.
      The optimal extraction conditions resulted in the highest H. erinaceus
      polysaccharides (HEP) yield, with a value 13.46 +/- 0.37%, which represented an
      increase of 67.72% compared to hot water extraction (HWE). The polysaccharides
      were characterized by FT-IR, SEM, CD, AFM, and GC. The results showed that HEP
      was composed of mannose, glucose, xylose, and galactose in a molar ratio of
      15.16:5.55:4.21:1. The functional groups of the H. erinaceus polysaccharides
      extracted by HWE and EAE were fundamentally identical but had apparent
      conformational changes.

PMID- 24299818
TI  - Telmisartan complex augments solubility, dissolution and drug delivery in
      prostate cancer cells.
AB  - Telmisartan (TEL) requires superior bioavailability in cancer cell compartments.
      To meet these challenges, we have synthesized a 2-HP-beta-CD-TEL complex with
      stability constant (Kc) of 2.39 * 10(-3)mM. The absence in the FTIR spectrum of 2
      HP-beta-CD-TEL complex of the characteristic peaks of TEL at 1,699 cm(-1)
      (carboxylic acid) and 741 and 756 cm(-1) (1,2-disubstituted benzene ring
      vibrations), is indicative of the encapsulation of TEL in the 2-HP-beta-CD
      cavity. DSC and PXRD also confirmed the synthesis and amorphous structure of
      complex. The interaction of TEL with 2-HP-beta-CD was examined by NMR and 2D
      ROESY which affirms the encapsulation of TEL in the 2-HP-beta-CD cavity in at
      least two orientations with equal binding energies. The complex also exhibited
      its superiority in both in vitro release and cytotoxicity experiments on prostate
      cancer, PC-3 cells as compared to free drug. These data warrant an in depth in
      vivo to scale-up the technology for the management of prostate cancer.

PMID- 24299819
TI  - Inclusion complex of barbigerone with hydroxypropyl-beta-cyclodextrin:
      preparation and in vitro evaluation.
AB  - The aim of this study was to improve the water solubility of barbigerone by
      complexing it with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The inclusion
      complexation behavior, characterization and interactions of barbigerone with HP
      beta-CD were investigated in both solution and the solid state by means of
      UV/VIS, (1)H NMR, FT-IR, PXRD, SEM. All the characterization information
      demonstrated the formation of barbigerone-HP-beta-CD (bar-HP-beta-CD) inclusion
      complex, and the bar-HP-beta-CD inclusion compounds exhibited different
      spectroscopic features and properties from barbigerone. The results demonstrated
      that the water solubility of barbigerone was notably increased in the presence of
      HP-beta-CD. Furthermore, preliminary in vitro cytotoxicity assay showed that bar
      HP-beta-CD still maintain the anticancer activity of barbigerone. These results
      suggest that HP-beta-CD will be potentially useful in the delivery of water
      insoluble anticancer agents such as barbigerone. 

PMID- 24299820
TI  - A heteropolysaccharide, L-fuco-D-manno-1,6-alpha-D-galactan extracted from
      Grifola frondosa and antiangiogenic activity of its sulfated derivative.
AB  - The tumor growth and metastasis are angiogenesis dependent, thus blockade of
      angiogenesis is a promising approach for treatment of cancer. Herein we reported
      the structural and biological features of a novel water-soluble polysaccharide
      named GFPW from the fruit body of Grifola frondosa. Chemical and spectral
      analysis revealed that GFPW with an average molecular weight of 15.7 kDa,
      possessed a backbone consisting of alpha-1,6-linked galactopyranosyl residues,
      with branches attached to O-2 of alpha-1,3-linked fucose residues and alpha
      terminal mannose. By the chlorosulfonic acid-pyridine method, we prepared a
      sulfated derivative of GFPW, Sul-GFPW, with a substitution degree of 0.33.
      According to the (13)C NMR spectrum, the substitution position was deduced at C-2
      and C-3. The angiogenesis assays in vitro showed that Sul-GFPW significantly
      inhibited endothelial cell proliferation in a dose- and time-dependent manner,
      and reduced endothelial cell migration and tube formation as well.

PMID- 24299821
TI  - Melt-processed poly(vinyl alcohol) composites filled with microcrystalline
      cellulose from waste cotton fabrics.
AB  - Waste cotton fabrics (WCFs), which are generated in a large volume from the
      textile industry, have caused serious disposal problem. Recycling WCFs into value
      added products is one of the vital measures for both environmental and economic
      benefits. In this study, microcrystalline cellulose (MCC) was prepared by acid
      hydrolysis of WCFs, and used as reinforcement for melt-processed poly(vinyl
      alcohol) (PVA) with water and formamide as plasticizer. The microstructure and
      mechanical properties of the melt-processed PVA/MCC composites were characterized
      by Fourier transform infrared spectra, Raman spectra, differential scanning
      calorimetry, thermal gravimetric analysis, X-ray diffraction, tensile tests and
      dynamic mechanical analysis. The results indicated that MCC could establish
      strong interfacial interaction with PVA through hydrogen bonding. As a result,
      the crystallization of PVA was confined and its melting temperature was
      decreased, which was beneficial for the melt-processing of PVA. Compared with the
      unfilled PVA, the PVA/MCC composites exhibited remarkable improvement in modulus
      and tensile strength. 

PMID- 24299822
TI  - Designing nanoemulsion templates for fabrication of dextrin nanoparticles via
      emulsion cross-linking technique.
AB  - The aim of this study was to prepare dextrin nanoparticles by emulsion cross
      linking technique. The nanoparticles were prepared from nanoemulsion templates
      produced by high power ultrasonication. The influence of hydrophilic-lipophilic
      balance (HLB), surfactant type and concentration, water content, and sonication
      time on the template size were examined in order to find optimal conditions for
      preparing dextrin nanoparticles. Nano-scaled templates were achieved when mixed
      surfactants (Span80/Tween80 and Span80/Brij30) at HLB 6 were used while using
      Span80 or other HLB values resulted in micron-sized templates. The smallest
      emulsion templates were achieved when using 7% (w/w) mixture of Span80/Tween80 at
      HLB 6, 15% (w/w) water, and sonication time of 30min. The spherical dextrin
      nanoparticles possessed a slight negative charge on the surface. FTIR spectra
      confirmed that dextrin was cross-linked by glyoxal. This study developed a novel
      way of formulating dextrin nanoparticles, which may prove to be useful in future
      for drug delivery. 

PMID- 24299823
TI  - Effect of cross-linking on physicochemical properties of tapioca starch and its
      application in soup product.
AB  - Physicochemical properties of cross-linked tapioca starch (CLTS) with different
      cross-linking levels and their application as a thickening agent in soups were
      studied. The CLTS was prepared by cross-linking native tapioca starch suspended
      in alkaline solution (41.67% (w/w), pH 11) using a mixture (99:1 (w/w) ratio) of
      sodium trimetaphosphate (STMP) and sodium tripolyphosphate (STPP) at different
      concentrations ranged from 0.25% to 6.0% (w/w of starch) at 45 degrees C for 3h.
      Starch paste clarity decreased with increasing concentration of STMP/STPP
      mixture. Variations of swelling power, solubility, pasting, gelatinization, and
      rheological properties of the CLTS were found. Thermogravimetric analysis
      exhibited higher thermal stability for the CLTS granules compared to the native
      one. Among the samples, the CLTS prepared using 1.0% STMP/STPP (1.0%-CLTS) and
      soup containing the 1.0%-CLTS exhibited the strongest gel characteristic and the
      greatest shear resistant properties. The 1.0%-CLTS improved the textural
      properties and sensory quality of soups. 

PMID- 24299824
TI  - Printing properties of the red reactive dyes with different number sulfonate
      groups on cotton fabric.
AB  - Cellulose fabric is an important printing substrate. Four red azo reactive dyes
      based on 1-naphthol-8-amino-3,6-disulfonic acid for cotton fabric printing were
      designed. Their UV-Vis spectra and printing properties for cotton were
      investigated. The relationship between the chemical structures of the dyes and
      their printing properties on cotton fabric was discussed. The results show that
      the color yield (K/S) values of the printed fabrics decreased with the increase
      of sulfonate groups, but the fixation and penetration of the reactive dyes on
      cotton fabric increased. The reactive dyes with fewer number sulfonate groups
      were sensitive to alkaline and urea. Whereas, the reactive dyes with numerous
      sulfonate groups were not sensitive to urea and had good leveling properties,
      penetration uniformity, and good wet fastness for cotton fabric. Surface
      wettability of all cotton fabrics printed with four dyes was excellent. It is
      possible to print cotton fabric urea-free using the reactive dyes with numerous
      sulfonate groups. 

PMID- 24299825
TI  - Degradation of cellulose at the wet-dry interface. II. Study of oxidation
      reactions and effect of antioxidants.
AB  - To better understand the degradation of cellulose upon the formation of a
      tideline at the wet-dry interface when paper is suspended in water, the
      production of chemical species involved in oxidation reactions was studied. The
      quantitation of hydroperoxides and hydroxyl radicals was carried out in reverse
      phase chromatography using triphenylphosphine and terephthalic acid,
      respectively, as chemical probes. Both reactive oxygen species were found in the
      tideline immediately after its formation, in the range of micromoles and
      nanomoles per gram of paper, respectively. The results indicate that hydroxyl
      radicals form for the most part in paper before the tideline experiment, whereas
      hydroperoxides appear to be produced primarily during tideline formation. Iron
      sulfate impregnation of the paper raised the production of hydroperoxides. After
      hygrothermal aging in sealed vials the hydroxyl radical content in paper
      increased significantly. When aged together in the same vial, tideline samples
      strongly influenced the degradation of samples from other areas of the paper
      (multi-sample aging). Different types of antioxidants were added to the paper
      before the tideline experiment to investigate their effect on the oxidation
      reactions taking place. In samples treated with iron sulfate or artificially
      aged, the addition of Irgafos 168 (tris(2,4-ditert-butylphenyl) phosphate) and
      Tinuvin 292 (bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6
      pentamethyl-4-piperidyl sebacate) reduced the concentration of hydroperoxides and
      hydroxyl radicals, respectively. Tinuvin 292 was also found to considerably lower
      the rate of cellulose chain scission reactions during hygrothermal aging of the
      paper. 

PMID- 24299826
TI  - Adsorptional removal of methylene blue by guar gum-cerium (IV) tungstate hybrid
      cationic exchanger.
AB  - Guar gum-cerium (IV) tungstate nanocomposite (GG/CTNC) cationic exchanger was
      synthesized using simple sol gel method. The GG/CTNC was characterized using X
      ray diffraction (XRD), Fourier transmission infrared spectroscopy (FTIR),
      scanning electron microscopy (SEM) and energy dispersive X-ray spectrophotometer
      (EDX). The XRD studies confirmed amorphous and fibrous in nature of GG/CTNC. The
      high percentage of oxygen in the nanocomposite material confirmed the
      functionality tungstate (WO4(-)). The ion exchange capacity of GG/CTNC for Na(+)
      ion was observed to be 1.30 mequivg(-1). The hybrid exchanger was used as
      potential adsorbent for the removal of methylene blue (MB) from aqueous system.
      The correlation coefficients value indicated a good fit of monolayer Langmuir
      model to the adsorption of methylene blue onto GG/CTNC. The adsorption kinetic
      study revealed that the adsorption process followed the pseudo second order
      kinetic. The Gibbs free energy (DeltaG) values confirmed the spontaneous nature
      of adsorption process.

PMID- 24299827
TI  - Acid pH-activated glycol chitosan/fullerene nanogels for efficient tumor therapy.
AB  - Glycol chitosan (GC) grafted with 2,3-dimethylmaleic acid (DMA) and fullerene
      (C60) conjugates (GC-g-DMA-g-C60) were developed for use in a photosensitizer
      prodrug. GC-g-DMA-g-C60 was prepared via the simple two-step chemical grafting
      reactions of (i) DMA to free amine groups of GC and (ii) hydroxyl groups of GC-g
      DMA to pipi carbon bonds of C60. This conjugate was self-assembled to form
      polysaccharidic nanogels consisting of a hydrophilic block (GC and DMA) and a
      hydrophobic block (C60). Here, GC-g-DMA-g-C60 nanogels also formed multi-nanogel
      aggregates due to the electrostatic interaction between the pendant carboxylic
      acid group (due to the DMA) and residual free amine group of GC at pH 7.4.
      Interestingly, the nanogel aggregates can be disintegrated at pH 5.0 due to the
      reduction of electrostatic interaction resulting from the cleavage of the DMA
      blocks at pH 5.0. Upon 670nm light illumination, photo-responsive properties of
      the nanogel aggregates allowed different singlet oxygen generation according to
      the pH condition: the reduced singlet oxygen generation (due to increased photo
      interference effect between C60 molecules close-packed in nanogel aggregates) at
      pH 7.4, but the elevated singlet oxygen generation (due to the disintegration of
      nanogel aggregates) at pH 5.0. GC-g-DMA-g-C60 nanogel aggregates responds to pH
      5.0 (approximately endosomal pH) can be a good candidate for endosomal pH
      targeting and in vivo photodynamic therapy in various malignant tumor cells.

PMID- 24299828
TI  - Hot-water extracts from the inner bark of Norway spruce with immunomodulating
      activities.
AB  - The inner bark of Norway spruce (Picea abies) was sequentially extracted with hot
      water at 100 degrees C, 140 degrees C and 160 degrees C. The hot-water extracts
      (IB 100 degrees C, IB 140 degrees C and IB 160 degrees C) contained pectic
      polysaccharides and showed immunostimulating activities. Structural analyses of
      their carbohydrate content, including glycosidic linkage analyses, revealed the
      presence of pectins with a large rhamnogalacturonan RG-I domain ramified with
      highly-branched arabinans. IB 100 degrees C also contained a large amount of
      terminal glucosyl residues, indicating the presence of highly substituted
      polymers. IB 160 degrees C was mainly composed of starch. The hot-water extracts
      were tested for two biological activities, namely complement fixation and
      macrophage stimulation. IB 100 degrees C exhibited the highest complement
      fixation activity, with a 1.7-times higher ICH50 than the control pectin, while
      IB 140 degrees C and IB 160 degrees C gave similar ICH50 values as the control.
      Macrophages were stimulated by IB 100 degrees C and IB 140 degrees C in a dose
      dependent manner, but not by IB 160 degrees C. IB 100 degrees C presented the
      highest activity toward macrophages, comparable to the control pectin. 

PMID- 24299829
TI  - Structure of highly substituted agarans from the red seaweeds Laurencia obtusa
      and Laurencia filiformis.
AB  - The water extracts from red seaweeds Laurencia obtusa and Laurencia filiformis
      comprise complex sulfated agarans. Those from L. obtusa have 3-linked beta-d
      galactose units in part sulfated on 2-position or methylated on 6-position, while
      the 4-linked units are mostly 3,6-anhydro-alpha-l-galactose and alpha-l-galactose
      6-sulfate, some of the latter units are substituted with beta-d-xylose on 3
      position, precluding alkaline cyclization. The 3-linked beta-d-galactose units of
      the agarans from L. filiformis are mostly sulfated on 2-position, but
      approximately half of these residues also carry the 4,6-O-(1-carboxyethylidene)
      group. The 4-linked 3,6-anhydro-alpha-l-galactose units are methylated or
      substituted in part with single stubs of beta-d-xylose on 2-position. This is the
      first time that substitution with xylose of 3,6-anhydro-alpha-l-galactose is
      reported. Besides, alpha-l-galactose 2-sulfate carrying single stubs of beta-d
      xylose on 3-position was also detected. These galactans have some common
      structural characteristics with those of other species of this genus, but also
      others that are specific for these species. 

PMID- 24299830
TI  - Control of mechanical properties of chitin nanofiber film using glycerol without
      losing its characteristics.
AB  - Surface-deacetylated chitin nanofiber films plasticized with glycerol were
      prepared to control mechanical properties. Nanofiber networks were able to retain
      excessive glycerol content up to 70% to obtain self-standing film. All films were
      flexible and highly transparent independent of glycerol content. Glycerol
      significantly decreased the Young's moduli and tensile strengths, and increased
      the fracture strain due to its plasticizing effect. At the same time, glycerol
      did not change the high transparency or the low thermal expansion of the
      nanofiber film. 

PMID- 24299831
TI  - Effect of silanization on chitosan porous scaffolds for peripheral nerve
      regeneration.
AB  - The aim of this study was to evaluate the feasibility of using 3
      aminopropyltriethoxysilane (APTE) silanization treatment for modification and
      biocompatibility of lyophilized chitosan porous scaffolds. The process is
      beneficial for biomaterial development due to its low toxicity and simplicity.
      The silanization treatment with low APTE concentration showed no significant
      influence on the morphology of chitosan scaffolds, while a skin-like surface was
      observed for the silanized scaffolds treated with high APTE concentration. The
      porosity and surface amino densities were increased after silanization whereas
      the swelling ratio was reduced, and the degradation ratio in PBS and anti-acid
      degradation properties of the silanized chitosan scaffolds were significantly
      improved. The in vitro Schwann cells culture demonstrated that the silanized
      scaffolds with 8% APTE could obviously facilitate the attachment and
      proliferation of Schwann cells, indicating great potential for the application in
      peripheral nerve regeneration. 

PMID- 24299832
TI  - Studies on the starch-water interactions between partially gelatinized corn
      starch and water during gelatinization.
AB  - The effect of moisture content on the interactions between water and partially
      gelatinized starch during gelatinization process was investigated. The
      interactions were probed using differential scanning calorimetry (DSC). The
      starch samples were partially gelatinized at 25 degrees C (S25), 64 degrees C
      (S64), 68 degrees C (S68) and 70 degrees C (S70) and the moisture contents were
      varied from 25% to 78% (w/w). The G endotherm was not observed and only the M1
      endotherm was observed in S64, S68 and S70 in the entire moisture content range.
      The G endotherm was not observed and only the M1 endotherm was observed at higher
      peak temperature in S25 when the moisture content was below 30% (w/w). The
      melting temperature of M2 endotherm in S70 was the highest among all the samples
      tested in the entire moisture content range. At water content>30% (w/w), S68 and
      S70 had lower amount of unfreezable water, while S64 had higher amount of
      unfreezable water. 

PMID- 24299833
TI  - Solubility enhancement of alpha-naphthoflavone by synthesized hydroxypropyl
      cyclic-(1->2)-beta-D-glucans (cyclosophoroases).
AB  - Rhizobium leguminosarum produces unbranched cyclic beta-1,2-glucans,
      cyclosophoraoses (Cys). In the present study, Cys were modified with
      hydroxypropyl groups via a one step chemical derivatization and the complexation
      ability and solubility enhancement of hydroxypropyl cyclosophoraoses (HP Cys)
      with alpha-naphthoflavone (alpha-NF) were investigated. In the presence of HP
      Cys, the aqueous solubility of alpha-NF greatly increased up to 257-fold. Complex
      formation of HP Cys and alpha-NF was confirmed by nuclear magnetic resonance
      (NMR), Fourier-transform infrared (FT-IR) spectroscopy, and differential scanning
      calorimetry (DSC). Furthermore, the morphological structure of alpha-NF with HP
      Cys was examined using scanning electron microscopy (SEM). A hypothetical model
      was proposed based on molecular dynamics (MD) simulations and a docking study of
      alpha-NF with HP Cys. Our results suggest that HP Cys form complexes with alpha
      NF and can be utilized as a promising solubilizer. This is the first study to
      identify carbohydrates that can enhance the solubility of alpha-NF. 

PMID- 24299834
TI  - One-pot synthesis of biocompatible superparamagnetic iron oxide
      nanoparticles/hydrogel based on salep: characterization and drug delivery.
AB  - This work describes synthesis of biocompatible magnetic iron oxide
      nanoparticles/hydrogel based on salep (MION-salep hydrogel) by a facile one-pot
      strategy. The prepared sample was characterized by techniques like scanning
      electron microscopy with energy dispersive X-ray analysis (SEM-EDAX),
      transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FT-IR), thermal gravimetric analysis (TGA), and vibrating sample magnetometer
      (VSM). The obtained MION had an 8 nm diameter with a narrow size distribution and
      was superparamagnetic with large saturation magnetization at room temperature.
      The most attractive feature of the obtained sample was its swelling properties
      under external magnetic field (EMF), different temperatures, and pHs. Moreover,
      MION-salep hydrogel showed ability to deferasirox release at pH=7 with non
      Fickian diffusion mechanism. An in vitro cytotoxicity study implied that the as
      synthesized sample is nontoxic.

PMID- 24299835
TI  - Chitosan/pectin/gum Arabic polyelectrolyte complex: process-dependent appearance,
      microstructure analysis and its application.
AB  - Novel chitosan/pectin/gum Arabic polyelectrolyte complex (PEC) solutions and
      membranes with various compositions were prepared for biomedical applications.
      The appearance of the PEC solutions, either clear or turbid, was process
      dependent and depended on how the three components were dissolved and mixed. The
      addition of gum Arabic to the chitosan and pectin significantly decreased the
      viscosities of the resultant PEC solutions due to the formation of globe-like
      microstructures that was accompanied by network-like microstructures and other
      molecular entanglements. The mechanical strength and hydrophilicity of the PEC
      membranes manufactured from the PEC solutions, especially for a weight ratio of
      84/8/8 (chitosan/pectin/gum Arabic), were enhanced compared to pure chitosan
      membranes. Moreover, the use of the 84/8/8 PEC membranes as a drug carrier
      exhibited steady and fairly complete release of a drug (insulin) for 6h. Based on
      these promising results, the chitosan/pectin/gum Arabic PEC membranes have great
      potential in controlled drug release applications. 

PMID- 24299836
TI  - Synthesis and characterization of dextran stabilized superparamagnetic iron oxide
      nanoparticles for in vivo MR imaging of liver fibrosis.
AB  - The field of medical imaging has recently seen rapid advances in the development
      of novel agents for enhancing image contrast. In particular, superparamagnetic
      iron oxide nanoparticles (SPIONs) with a variety of surface properties have been
      tried as effective contrast agents for magnetic resonance imaging, but with major
      side effects. In this study, the surface chemistry of SPIONs of size 12 nm was
      modified with high molecular weight dextran to yield particles of size 50 nm,
      without compromising the magnetic properties. A systematic characterization of
      the material for its size, coating efficiency, magnetic properties and
      biocompatibility has been carried out. The magnetic relaxivity as evaluated on a
      1.5 T clinical magnet showed r2/r1 ratio of 56.28 which is higher than that
      reported for any other dextran stabilized ironoxide nanoparticles. Liver uptake
      and magnetic resonance imaging potential of dextran stabilized SPIONs (D-SPIONs)
      has been evaluated on liver fibrosis induced animal model, which is further
      supported by histopathology results.

PMID- 24299837
TI  - A review on engineering of cellulosic cigarette paper to reduce carbon monoxide
      delivery of cigarettes.
AB  - In cigarette production, the cellulosic paper essentially derived from flax
      fibers or other fiber materials is used as the wrapping material. During smoking
      of cigarettes, the highly toxic carbon monoxide is produced. To decrease the
      amount of carbon monoxide emission in the mainstream smoke, the engineering of
      all cigarette components including cellulosic cigarette paper and tobacco column
      is critical. This review summarizes the concepts related to engineering of
      cigarette paper. These mainly include permeability control, increased use of burn
      additives, optimization of fiber basis weight, engineering of calcium carbonate
      fillers, and incorporation of catalysts/oxidants. In particular, catalytic and/or
      oxidative conversion of carbon monoxide to carbon dioxide has been very widely
      reported. The control of permeability/diffusivity of cigarette paper is also of
      critical importance for enhanced diffusion of carbon monoxide out of the
      cigarette. The development of new concepts and combination of various concepts
      may lead to breakthroughs in this area. 

PMID- 24299838
TI  - Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity
      and cytotoxicity.
AB  - In this paper, the structural effects of two main red seaweed polysaccharides
      (agarose and carrageenan) and their sulfated derivatives on the anticoagulant
      activity and cytotoxicity were investigated. The substitution position rather
      than the substitution degree of sulfate groups shows the biggest impact on both
      the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6
      anhydro-alpha-d-Galp is the most favorable position for substitution, whereas C-6
      of beta-d-Galp is the most disadvantageous. Moreover, the secondary structures of
      glycans also play a key role in biological activities. These demonstrations
      warrant that the red seaweed polysaccharides should be seriously considered in
      biomedical applications after carefully tailoring the sulfate groups. 

PMID- 24299839
TI  - Microwave assisted extraction of pectin from waste Citrullus lanatus fruit rinds.
AB  - In this present study, microwave-assisted extraction (MAE) was applied to
      extraction of pectin from waste Citrullus Lanatus fruit rinds. Extraction
      parameters which are employed in this study are microwave power (160-480 W),
      irradiation time (60-180s), pH (1-2) and solid-liquid ratio (1:10-1: 30 g/ml) and
      they were optimized using a four factor three levels Box-Behnken response surface
      design (BBD) coupled with desirability function methodology. The results showed
      that, all the process variables have significant effect on the extraction yield
      of pectin. Optimum MAE conditions for the highest pectin yield from waste C.
      Lanatus fruit rinds (25.79%) were obtained with microwave power of 477 W,
      irradiation time of 128 s, pH of 1.52, solid-liquid ratio of 1:20.3g/ml
      respectively. Validation experiment results were well agreed with predicted
      value.

PMID- 24299840
TI  - Changes in accessibility of cellulose during kraft pulping of wood in deuterium
      oxide.
AB  - Fresh birch chips were treated with different concentrations of sodium hydroxide
      and sodium sulfide in deuterium oxide in typical kraft pulping conditions and the
      extent of irreversible deuteration of the chips/pulps was followed by Fourier
      transform infrared (FT-IR) spectroscopy. Water retention values (WRV) of pulps
      were measured to evaluate accessibility of cellulose. The kraft pulping with
      deuterium oxide led to significant proton-deuterium exchange that was not
      reversed when the chips/pulps were washed with water. The deuteration followed a
      first order dynamics with a maximum obtained in the beginning of delignification
      stage. Higher dosages of effective alkali resulted in a higher degree of
      deuteration and lower WRV. An inverse relationship between the extent of
      deuteration and WRV suggests that both were induced by cellulose microfibril
      aggregation. Results also indicate that hemicellulose dissolution plays an
      important role in the induction of cellulose microfibril aggregation, while
      lignin dissolution has less influence. 

PMID- 24299841
TI  - Synthesis and characterisation of starch grafted superabsorbent via 10 MeV
      electron-beam irradiation.
AB  - A starch-graft-polyacrylamide (St-g-PAM) superabsorbent crosslinked by N,N'
      methyl bisacrylamide (MBA) was prepared using 10 MeV simultaneous electron beam
      irradiation at room temperature and subsequent alkaline hydrolysis. The effects
      of the irradiation dose, acryliamide-to-anhydroglucose unit (AM-to-AGU) ratio and
      crosslinker amount on the properties of the obtained polymers were evaluated. The
      structure of the graft copolymer was confirmed by Fourier transform infrared
      spectroscopy (FTIR) and scanning electron microscope (SEM). Optimisation
      treatments were carried out and found for a total dose of 8 kGy, an AM-to-AGU
      ratio of 4.5 mol mol(-1) and a crosslinker-to-AM ratio of 0.4%mol mol(-1). The
      obtained superabsorbent polymer showed the maximum absorptions of 1,452 gg(-1)
      and 83 gg(-1) for distilled water and saline solution, respectively (relative to
      its own dry weight). The results suggest 10 MeV electron beam irradiation is more
      efficient than gamma-ray irradiation due to its higher energy and dose rate.

PMID- 24299842
TI  - The system of fucoidans from the brown seaweed Dictyota dichotoma: chemical
      analysis and antiviral activity.
AB  - Room-temperature acid (pH 2) extraction of Dictyota dichotoma thalli yielded 2.2%
      of sulfated polysaccharides. Further extraction with the same solvent at 70
      degrees C was conducted sequentially for nine times, with a total yield of 7.2%.
      Fucose was the main monosaccharide only in the room-temperature extract (EAR) and
      in the first 70 degrees C extract (EAH1). The remaining fractions showed
      increasing amounts of mannose (the main neutral monosaccharide), xylose and
      uronic acids. Fractionation by means of cetrimide precipitation and redissolution
      in increasing sodium chloride solutions has allowed obtaining several
      subfractions from each extract. The fractions redissolved at lower NaCl
      concentrations have large amounts of uronic acids and lesser sulfate contents,
      whereas those redissolved at higher NaCl concentrations are heavily sulfated and
      have low uronic acid contents. For the fucose-rich extracts (EAR and EAH1),
      fractionation leads to uronoxylomannofucan-rich and galactofucan-rich fractions.
      The remaining extracts gave rise to complex mixtures, with mannose and uronic
      acid-rich polysaccharides. Moderate inhibitory effect against herpes virus (HSV
      1) and Coxsackie virus (CVB3) were found for the galactofucan-rich fractions.
      Most of the other fractions were inactive against both viruses, although some
      xylomannan-rich fractions were also active against HSV-1. 

PMID- 24299843
TI  - The green adsorption of chitosan tripolyphosphate nanoparticles on cotton fiber
      surfaces.
AB  - Chitosan nanoparticles (chitosan NP) were effectively incorporated onto cotton
      fiber surfaces during a green adsorption without any cross-linking agents in this
      work. The interactions between cotton fibers and chitosan NP during the green
      adsorption were investigated by Fourier transform infrared spectroscopy (FTIR), X
      ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), thermogravimetric
      derivative thermogravimetry (TG-DTG) and scanning electron microscopy (SEM) in
      detail. The results indicated that the intermolecular hydrogen bond interactions
      exited between the hydroxyl groups of cotton fibers and the amino groups of
      chitosan NP, and progressively enhanced with the increase in chitosan NP mass
      concentrations. After chitosan NP adsorption, the acidity of fibers augmented and
      the crystallinity index of fibers declined owing to the increasing interactions.
      In addition, the hydrophobic interactions occurred between chitosan NP and
      crystalline cotton fibers, thereby resulting in the preferential adsorption onto
      the hydrophobic (200) crystallographic plane. 

PMID- 24299844
TI  - Protective effect of polysaccharides on simulated microgravity-induced functional
      inhibition of human NK cells.
AB  - Polysaccharides are believed to be strong immunostimulants that can promote the
      proliferation and activity of T cells, B cells, macrophages and natural killer
      (NK) cells. This study aimed to investigate the effects of five polysaccharides
      (Grifola frondosa polysaccharide (GFP), lentinan (LNT), G. lucidum polysaccharide
      (GLP), Lycium barbarum polysaccharide (LBP) and yeast glucan (YG)) on primary
      human NK cells under normal or simulated microgravity (SMG) conditions. Our
      results demonstrated that polysaccharides markedly promoted the cytotoxicity of
      NK cells by enhancing IFN-gamma and perforin secretion and increasing the
      expression of the activating receptor NKp30 under normal conditions. Meanwhile
      polysaccharides can enhance NK cell function under SMG conditions by restoring
      the expression of the activating receptor NKG2D and reducing the early apoptosis
      and late apoptosis/necrosis. Moreover, the antibody neutralization test showed
      that CR3 may be the critical receptor involved in polysaccharides induced NK
      cells activation. These findings indicated that polysaccharides may be used as
      immune regulators to promote the health of the public and astronauts during space
      missions. 

PMID- 24299845
TI  - Inclusion complex of sulfadimethoxine with cyclodextrins: preparation and
      characterization.
AB  - The inclusion complexation behavior, characterization and binding ability of
      sulfadimethoxine (SDMO) with alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin
      (beta-CD) have been investigated both in solution and solid state by means of
      absorption, fluorescence, time-resolved fluorescence, (1)H NMR, FT-IR, DSC, SEM,
      TEM, XRD and molecular modeling methods. The spectral shifts revealed that the
      part of pyrimidine and aniline rings of SDMO are entrapped in the CD cavity. The
      stoichiometric ratio and association constant were determined by Benesi
      Hildebrand plots and spectroscopic studies respectively. FT-IR spectroscopy was
      used to compare inclusion systems with physical mixtures, and demonstrated the
      complex formation in the solid state. The morphology and size of the
      nanoparticles of SDMO/CD complexes in aqueous solution were observed by TEM. The
      DSC analysis showed that the thermal stability of SDMO was enhanced in the
      presence of CD. Investigations of energetic and thermodynamic properties by PM3
      method confirmed the stability of the inclusion complexes. 

PMID- 24299846
TI  - Functionality of porous starch obtained by amylase or amyloglucosidase
      treatments.
AB  - Porous starch is attracting very much attention for its absorption and shielding
      ability in many food applications. The effect of two different enzymes, fungal
      alpha-amylase (AM) or amyloglucosidase (AMG), on corn starch at sub
      gelatinization temperature was studied as an alternative to obtain porous starch.
      Biochemical features, thermal and structural analyses of treated starches were
      studied. Microscopic analysis of the granules confirmed the enzymatic
      modification of the starches obtaining porous structures with more agglomerates
      in the case of AMG treated starches. Several changes in thermal properties and
      hydrolysis kinetics were observed in enzymatically modified starches. Hydration
      properties were significantly affected by enzymatic modification being greater
      influenced by AMG activity, and the opposite trend was observed in the pasting
      properties. Overall, results showed that enzymatic modification at sub
      gelatinization temperatures really offer an attractive alternative for obtaining
      porous starch granules to be used in a variety of foods applications. 

PMID- 24299847
TI  - The influence of the starch component on thermal radical generation in flours.
AB  - Transition metal ions and radicals in flours of various botanical origins with
      different content of starch have been studied by EPR before and after thermal
      treatment. The amounts of metal ions, have been determined by ICP OES.
      Simulations of EPR spectra have revealed the presence of several types of
      radicals (carbon-centred, tyrosyl and semiquinone) localized in starch and
      protein fractions of flours. Thermal treatment of flours significantly increased
      the amount of radicals with a simultaneous decrease of the signal intensity of
      transition metal ions. The proposed mechanism of thermal generation of stable
      organic radicals was associated with the redox processes involving transition
      metal ions, which facilitated the formation of radicals. The dependence between
      the way starch is treated and the mechanism of radical formation was also shown. 

PMID- 24299848
TI  - Prevention of browning of depolymerized chitosan obtained by gamma irradiation.
AB  - In this paper, effect of oxygen and pH on the browning of chitosan exposed to
      gamma radiation was investigated. It was found that oxygen and pH value could
      play important roles in the inhibiting browning of irradiated chitosan. When the
      pH value of chitosan solution was below 3.0, sufficient oxygen could inhibit
      browning of irradiated chitosan in aqueous solution. As a result of irradiation
      of chitosan solution (pH<3) with sufficient oxygen, the irradiated chitosan
      solutions obtained were colorless and pellucid. FT-IR, (13)C NMR, and UV-vis
      spectra confirmed that the irradiation in the presence of oxygen cannot result in
      chemical modification of irradiated chitosan. An effective technology was
      developed for the inhibition of browning of irradiated chitosan during
      depolymerization of chitosan by gamma irradiation. 

PMID- 24299849
TI  - Preparation and detailed NMR analyses of a series of oligo-alpha-carrageenans.
AB  - Standard oligo-iota-carrageenans were produced with iota-carrageenases isolated
      from the marine bacteria Alteromonas fortis and Pseudolalteromonas atlantica. The
      carrageenans were then desulfated using a 4S-carrageenan-sulfatase purified from
      P. atlantica. Using chromatography and NMR analyses, we characterized a series of
      new standard neo-alpha-carrageenan oligosaccharides.

PMID- 24299850
TI  - Isolation of an arabinogalactan from Endopleura uchi bark decoction and its
      effect on HeLa cells.
AB  - Endopleura uchi is a native plant from the Amazon used in popular medicine to
      treat myomas. A crude polysaccharide (AGb) obtained from E. uchi bark decoction
      was purified, yielding a type II arabinogalactan (AG) that was characterized by
      chemical and spectroscopic methods. AG was evaluated for its cytotoxic effects on
      HeLa cells. AG (5-500 MUg/ml) reduced cell viability at 48 and 72 h
      (approximately 20%) but not in a dose-dependent manner. Cell proliferation was
      also reduced by AG, with a 25% inhibition (100 MUg/ml) at 72 h. The results
      suggest that the cytotoxicity exhibited by AG does not involve pathways related
      to the cell cycle.

PMID- 24299851
TI  - Kenaf bast cellulosic fibers hierarchy: a comprehensive approach from micro to
      nano.
AB  - Cellulosic fibers from kenaf bast were isolated in three distinct stages.
      Initially raw kenaf bast fibers were subjected to an alkali pulping process. Then
      pulped fibers undergone a bleaching process and finally both pulped and bleached
      fibers were separated into their constituent nanoscale cellulosic fibers by
      mechanical shearing. The influence of each treatment on the chemical composition
      of fibers was investigated. Moreover morphology, functional groups,
      crystallinity, and thermal behavior of fiber hierarchy at different stages of
      purification were studied using scanning and transmission electron microscopies,
      Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and
      thermogravimetric analysis (TGA), respectively. Microscopy studies revealed that
      applied procedures successfully isolated nanoscale cellulosic fibers from both
      unbleached and bleached pulps. Chemical composition analysis and FTIR
      spectroscopy showed that lignin and hemicellulose were almost entirely removed by
      the applied treatments. XRD and TGA analyses demonstrated progressive enhancement
      of properties in fibers, hierarchically, in going from micro to nano scale.
      Interestingly no significant evolution was observed between obtained data of
      characterized ubnleached and bleached nanofibers. 

PMID- 24299852
TI  - Polyethylene glycol as a novel solvent for extraction of crude polysaccharides
      from Pericarpium granati.
AB  - Polyethylene glycol aqueous solution (PEGs), an environmentally friendly solvent
      was used, for the first time, to develop an extraction method for crude
      polysaccharides from pericarpium granati with ultrasonic-microwave-assisted
      extraction (UMAE). Compared with other extraction solvents, PEGs, especially
      PEG400, displayed a higher extraction yield. The extraction conditions were an
      ultrasonic power of 240 W, a microwave power of 365 W, a PEG400 concentration of
      30% and a ratio of liquid to raw material of 20 mL/g, optimized by using Box
      Behnken experimental design. Under these conditions, an extraction yield of 7.94
      +/- 0.3% (n=3) was obtained, which is about 25% higher than that with water as a
      solvent, and the polysaccharides content in pericarpium granati was 6.56 +/- 0.01
      mg/g expressed as glucose.

PMID- 24299853
TI  - Isolation and characterization of hydrophobic compounds from carbohydrate matrix
      of Pistacia atlantica.
AB  - The present work is focused on the optimization of hydrophobic compounds
      extraction process from the carbohydrate matrix of Iranian Pistacia atlantica
      seed at laboratory level using ultrasonic-assisted extraction. Response surface
      methodology (RSM) was used to optimize oil seed extraction yield. Independent
      variables were extraction temperature (30, 45, 60, 75 and 90 degrees C),
      extraction time (10, 15, 20, 25, 30 and 35 min) and power of ultrasonic (20, 40,
      60, 80 and 100 W). A second order polynomial equation was used to express the oil
      extraction yield as a function of independent variables. The responses and
      variables were fitted well to each other by multiple regressions. The optimum
      extraction conditions were as follows: extraction temperature of 75 degrees C,
      extraction time of 25 min, and power of ultrasonic of 80 W. A comparison between
      seed oil composition extracted by ultrasonic waves under the optimum operating
      conditions determined by RSM for oil yield and by organic solvent was reported.

PMID- 24299854
TI  - Xanthan hydrogel films: molecular conformation, charge density and protein
      carriers.
AB  - In this article the molecular conformation of xanthan chains in hydrogel films
      was investigated by means of circular dichroism, showing substantial differences
      between xanthan hydrogel prepared in the absence (XNT) and in the presence of
      citric acid (XCA). The xanthan chains in XNT hydrogels films presented ordered
      conformation (helixes), while in XCA they were in the disordered conformation
      (coils), exposing a larger number of carboxylate groups than XNT. The large
      charge density in XCA hydrogels was evidenced by their behavior under variable
      ionic strength. Studies about the application of XNT and XCA for loading and
      delivering of bovine serum albumin (BSA) and lysozyme (LYZ) showed that both
      events are controlled by hydrogels and proteins net charge, which can be
      triggered by pH. The preservation of LYZ native conformation after hydrogel
      loading explained the substantial bactericidal activity of LYZ loaded hydrogels
      and enables their use as active wound dressings. 

PMID- 24299855
TI  - Regenerated cellulose fibers spun-dyed with carbon black/latex composite
      dispersion.
AB  - A carbon black (CB)/latex composite was prepared by the method of miniemulsion
      polymerization for use as a colorant for spun dyeing of regenerated cellulose
      fibers. Analysis of experimental results revealed that the CB/latex composite had
      a small particle size and a narrow particle size distribution which were
      important to ensure a stable dispersion being later added to spinning solution. A
      good stability of the prepared CB/latex composite dispersion in the spinning
      solution indicated that it was highly possible to use the CB/latex composite as a
      colorant for spun dyeing of regenerated cellulose fibers. When a 3.5% mass ratio
      of CB/latex composite to cellulose was used for spun dyeing, the spun-dyed fibers
      had the highest tensile strength, breaking elongation and color strength. The
      rubbing and washing color fastnesses of spun-dyed regenerated cellulose fibers
      could satisfy requirements of most textiles. This study provided a new insight
      into producing spun-dyed regenerated cellulose with a novel colorant. 

PMID- 24299856
TI  - New approaches to improving thermal regulating property of cellulosic fabric.
AB  - To enhance the thermoregulation property of cotton fabric, new materials have
      been prepared to be used for encapsulating phase change materials (PCMs). The new
      material has been prepared via esterification reaction between different
      carboxylic acids and different fatty acids crossed with diglycol compounds, these
      materials were characterised to be used as hosting materials for octadecane,
      which is heat storing material suitable for textile applications. FT-IR and DSC
      analysis were used to characterise the prepared hosting material. The prepared
      materials have special shape which has different cavity distance between its side
      chains, and also have a reactive group on the backbone of its structure which
      make these materials able to react chemically with cotton fabric to help it to be
      not leakage from the treated surface (permanent) and the material will be stable
      on the fibre surface even after washing. When applied onto textile materials, the
      treated fabric shows good thermoregulation property. 

PMID- 24299857
TI  - Isolation and characterization of starch obtained from Brosimum alicastrum Swarts
      seeds.
AB  - In this paper, the Ramon starch was isolated and its chemical composition and
      physical and microscopic characteristics were determined. Corn starch was used as
      reference. In general, the proximal composition was similar between starches
      studied. Ramon starch granules were oval-spherical and rounded with sizes between
      6.5 and 15 MUm. Starch purity was high (92.57%) with amylose content of 25.36%.
      The gelatinization temperature was 83.05 degrees C and transition enthalpy was
      21.423 J/g. At 90 degrees C, solubility was 20.42%, swelling power 17.64 g
      water/gstarch and water absorption capacity was 13 gwater/gstarch. The pH,
      clarity and color (Hue angle) of Ramon starch were higher to those reported for
      corn starch. The results achieved suggest that Ramon starch has potential for
      application in food systems requiring high processing temperatures and it is also
      a promising option for use in the manufacture of biodegradable materials.

PMID- 24299858
TI  - Influence of polymer network parameters of tragacanth gum-based pH responsive
      hydrogels on drug delivery.
AB  - The present article deals with design of tragacanth gum-based pH responsive
      hydrogel drug delivery systems. The characterization of hydrogels has been
      carried out by SEMs, EDAX, FTIR, (13)C NMR, XRD, TGA/DTA/DTG and swelling
      studies. The correlation between reaction conditions and structural parameters of
      polymer networks such as polymer volume fraction in the swollen state (phi),
      Flory-Huggins interaction parameter (chi), molecular weight of the polymer chain
      between two neighboring cross links (M-c), crosslink density (rho) and mesh size
      (xi) has been determined. The different kinetic models such as zero order, first
      order, Higuchi square root law, Korsmeyer-Peppas model and Hixson-Crowell cube
      root model were applied and it has been observed that release profile of
      amoxicillin best followed the first order model for the release of drug from the
      polymer matrix. The swelling of the hydrogels and release of drug from the drug
      loaded hydrogels occurred through non-Fickian diffusion mechanism in pH 7.4
      solution. 

PMID- 24299859
TI  - Water soluble exo-polysaccharide from Syncephalastrum racemosum, a strong inducer
      of plant defence reactions.
AB  - This study examines the production, characterization and bioactivity on plant
      cell cultured in vitro of exopolysaccharides (EPS) from Syncephalastrum racemosum
      CBS 443.59. Firstly, the influence of the fungus culture condition in shake
      flasks (pH, temperature and different carbon and nitrogen sources) on EPS and
      biomass production was evaluated. In order to enhance EPS production, a new
      protocol based on two-stage pH fermentation in a 3 L stirred fermentor was
      developed. Under this condition, EPS production increased by 3.55 times, compared
      to a constant pH process, reaching a maximal EPS concentration of 2.62 g/L.
      Structurally, the EPS contains a polyglucuronic acid backbone, linked essentially
      with mannose and fucose units and some galactose and glucose units. The
      bioactivity of EPS as inducer of defence reactions in plant suspension-cultured
      cells was also studied. Our results show, for first time, that EPS from S.
      racemosum CBS 443.59 induces, depending on the concentration, PAL activation and
      H2O2 synthesis in Arabidopsis thaliana cell suspensions.

PMID- 24299860
TI  - Synthesis and characterization of bacterial cellulose sulfates using a
      SO3/pyridine complex in DMAc/LiCl.
AB  - Various sodium bacterial cellulose sulfates (SBCS) were prepared via the
      homogeneous sulfation of bacterial cellulose (BC) with a SO3/pyridine (Py)
      complex in a dimethyl acetamide/lithium chloride solution. The SBCSs were
      characterized using Fourier transform infrared spectroscopy, X-ray diffraction
      (XRD), carbon nuclear magnetic resonance spectroscopy, gel permeation
      chromatography, elemental analyses, and thermal gravimetric analyses. A variety
      of conditions (including various amounts of SO3/Py, temperatures, and reaction
      times) were utilized to obtain SBCSs with DS values that ranged from 0.10 to
      1.50. The XRD profiles indicated that the SBCSs had a cellulose II analog
      polymorphous structure. The differences between BC and microcrystalline cellulose
      (MC) were studied in their respective reactions. BC is more reactive than MC in
      both the sulfation and depolymerization processes. The order of reactivity for
      COH is C6>C2>C3 for both BC and MC. Cellulose sulfates with DS values >0.31 were
      soluble in deionized water. 

PMID- 24299861
TI  - Removal of pigments from aqueous solution by a calcium alginate-grape marc
      biopolymer: a kinetic study.
AB  - In this work, the potential use of a biopolymer based on grape marc entrapped in
      calcium alginate beads for the removal of pigments from an agro industrial
      effluent was evaluated. The parameters that affect the pigment adsorption such as
      pH (3.5-7.0), temperature (10-40 degrees C) and initial pigment concentration
      (6.9-55.1mg/L) were studied by applying an incomplete factorial design. The
      dependent variables evaluated consisted of color effluent parameters from CIELAB
      and Tristimulus system, as well as the concentration of pigments in the
      wastewater after the adsorption treatment. The most significant independent
      variables tested were the pigments concentration followed by pH, whereas
      temperature had a negligible effect on the adsorption process. Moreover, at the
      optimal operational conditions (pH 3.5 and room temperature) kinetic studies were
      carried out by applying pseudo-first order, pseudo-second order, Chien-Clayton
      and intraparticle diffusion models, observing a good agreement between
      theoretical and experimental results. 

PMID- 24299862
TI  - Green synthesis of xanthan conformation-based silver nanoparticles: antibacterial
      and catalytic application.
AB  - Silver nanoparticles (Ag NPs) were green synthetized using xanthan gum (XG)
      dissolved in water as reducing and capping agent for the first time. The
      structure, morphology, and size of Ag NPs in XG aqueous solutions were
      investigated with UV-vis spectroscopy, transmission electron microscopy and
      Fourier transform infrared. The results indicated Ag NPs were integrated
      successfully in the XG matrix and the optical properties and morphology of Ag NPs
      could be regulated by the synthesis condition. The aggregation of the XG-bonded
      Ag NPs increased with storage, whereas the size barely changed. The assemble
      behavior was related to the XG conformation transition of denaturation and
      renaturation. The one spot formed Ag NPs showed favorable antibacterial effect on
      Escherichia coli and Staphyloccocus aureus and excellent catalytic capability of
      4-nitrophenol reduction. This work provided a feasible method to detect the
      biopolymer space structure transition through the intensity of metal
      nanoparticles labeled on the chain. 

PMID- 24299863
TI  - Physicochemical characterization of a high molecular weight bioactive beta-D
      glucan from the fruiting bodies of Ganoderma lucidum.
AB  - A purified polysaccharide coded as GLP20 was obtained by precipitating a hot
      water extract from Ganoderma lucidum fruiting bodies with 20% (V/V) ethanol. Its
      total carbohydrate content was 95.9%. Structural analysis showed that GLP20 was a
      beta-(1->3)-linked d-glucan with a (1->6)-beta-d-glucopyranosyl side-branching
      unit on every third residue. Cell culture study revealed that GLP20 can
      significantly increase NO production of RAW264.7 macrophages. The analysis of
      light scattering and high performance size exclusion chromatography (HPSEC)
      showed that the molecular weight and polydispersity of GLP20 was 3.75 * 10(6)Da
      and 1.36, respectively. GLP20 had a rigid chain conformation in aqueous solution.
      A conformation transition occurred in the alkaline solution with NaOH
      concentration larger than 0.15M. The transition from ordered structure to single
      chain happened when GLP20 was heated above 135 degrees C in water solution and
      was irreversible as demonstrated by differential scanning calorimetry (DSC).
      GLP20 existed as random coils in DMSO.

PMID- 24299864
TI  - Biosynthesis of levan by levansucrase from Bacillus methylotrophicus SK 21.002.
AB  - A new strain SK 21.002 which could produce intracellular levansucrase was
      isolated from beet sugar growing soil. It was identified as Bacillus
      methylotrophicus based on the sequence analysis of the 16S rRNA and the
      morphological characteristic. The structure of levan biosynthesized from the
      levansucrase was determined to be connected through beta-(2->6) linkages with
      fructofuranosyl residues. The molecular weight of the product was between 4 and 5
      kDa. The optimal conditions to produce levan using the levansucrase were studied.
      The presence of Mg(2+) could increase the yield of levan. The yield of levan
      reached about 100g/L with the enzyme under the optimum conditions.

PMID- 24299865
TI  - Sulfated modification can enhance antiglycation abilities of polysaccharides from
      Dendrobium huoshanense.
AB  - Dendrobium huoshanense is an important edible-medicinal plant with high
      nutritional values and health functions. A homogenous polysaccharide (DHPD1) with
      molecular weight of 3.2 * 10(3)Da was extracted from D. huoshanense, which was
      mainly composed of glucose, arabinose, galactose, mannose and xylose.
      Chlorosulfonic acid-pyridine (CSA-Pyr) method was performed to modify the
      structure of DHPD1. In order to get a high degree of substitution (DS), sulfated
      modification conditions were optimized by response surface methodology. The
      maximum DS of 1.473 was obtained when the reaction condition was fixed at
      reaction temperature 60 degrees C, reaction time 160 min and volume ratio of Pyr
      to CSA 2:1. NMR spectra revealed that this sulfation occurred to C-2 and C-6 of
      glycosyl residues in DHPD1. After 28 days of incubation, the sulfated DHPD1 at
      1.0mg/mL showed the inhibitory ability of 58.5%, which increased by 16.2% and
      52.5% than that of aminoguanidine and DHPD1 at the same dosage.

PMID- 24299866
TI  - Characterization, antioxidant and hepatoprotective activities of polysaccharides
      from Ilex latifolia Thunb.
AB  - Crude polysaccharides from the leaves of Ilex latifolia Thunb (ILPS) was
      fractionated by DEAE cellulose-52 chromatography, affording four fractions of
      ILPS-1, ILPS-2, ILPS-3 and ILPS-4 in the recovery rates of 32.3, 20.6, 18.4 and
      10.8%, respectively, based on the amount of crude ILPS used. The four fractions
      were mainly composed of arabinose and galactose in monosaccharide composition.
      Compared with ILPS-1 and ILPS-2, ILPS-3 and ILPS-4 had relative higher contents
      of sulfuric radical and uronic acid. The antioxidant activities in vitro of ILPS
      decreased in the order of crude ILPS>ILPS-4>ILPS-3>EPS-2>ILPS-1. Furthermore, the
      administration of crude ILPS significantly prevented the increase of serum
      alanine aminotransferase and aspartate aminotransferase levels, reduced the
      formation of malondialdehyde and enhanced the activities of superoxide dismutase
      and glutathione peroxidase in carbon tetrachloride-induced liver injury mice. The
      results suggested that ILPS should be a potent natural polymer with antioxidant
      and hepatoprotective activities.

PMID- 24299867
TI  - Citric acid crosslinking of paper products for improved high-humidity
      performance.
AB  - Fibre crosslinking with polycarboxylic acids can be used to improve certain
      properties of paper products, including wet tensile and compressive strength. In
      the present work it was proposed that citric acid (CA) crosslinks the cellulosic
      fibres of linerboard by self-catalysed esterification of cellulosic hydroxyl
      groups, which makes an additional catalyst unnecessary. An increase in CA dose or
      curing temperature increased linerboard compressive strength. In CA-treated
      corrugated board most of the applied CA was esterified with fibres while some CA
      thermolysis products were also present. A significant portion of the applied CA
      was unaccounted for. The deficit was attributed to thermolysis to give volatile
      anhydrides of unsaturated acids. Under cyclic humidity and static compressive
      loading, CA-treated corrugated boxes showed a greater than three-fold increase in
      resistance to compressive creep, showing that CA treatment can be used to extend
      the lifetime of corrugated boxes used for horticultural produce storage. 

PMID- 24299868
TI  - Efficient extraction and characterization of polymeric hemicelluloses from hybrid
      poplar.
AB  - Hemicelluloses were isolated from hybrid poplar with the single-step alkaline
      extraction. Neutralization and subsequent ethanol precipitation were used to
      recover them. Their structures were investigated using sugar analysis, Fourier
      transform infrared and (13)C nuclear magnetic resonance spectroscopy. The
      hemicelluloses were characterized by particle size analyzer, gel permeation
      chromatography and thermogravimetric analyzer. 36.4% and 50.4% of the original
      hemicelluloses were isolated in the form of polymer by neutralization and
      precipitation, respectively. The hemicellulosic fraction (HA) by neutralization
      was more homogeneous in sugar components than the one (HB) by precipitation.
      However, hemicellulose isolated by both of the process has chemical structure, as
      were (4-O-methylglucurono)-d-xylans. The weight average molecular mass of HA was
      17,480 g mol(-1), higher than one of HB (14,670 g mol(-1)) and they were both
      with a low polydispersity. HA had lower zeta potential and higher thermal
      stability than HB. Therefore, the procedures in this study were efficient for the
      isolation and the recovery of polymeric hemicelluloses with different properties.

PMID- 24299869
TI  - Chemically sulfated galactomannan from Dimorphandra gardneriana seed:
      characterization and toxicity evaluation.
AB  - Dimorphandra gardneriana galactomannan (DG) was sulfated in pyridine:formamide
      using chlorosulfonic acid as the sulfation agent. The degree of substitution was
      0.32, determined from the sulfur percentage. Confirmation of sulfation was
      obtained by FTIR spectroscopy through the presence of an asymmetrical SO
      stretching vibration at 1,259 cm(-1). NMR data showed that the sulfation occurred
      on primary hydroxyl groups. NMR and GPC data indicate degradation during reaction
      with elimination of galactose. At the maximum tested concentration of 1,000
      MUg/mL, unmodified DG polysaccharide did not show a statistically significant
      cytotoxicity in Vero cells by the MTT method. Therefore, the CC50>1,000 MUg/mL
      obtained for the sulfated polysaccharides from D. gardneriana in Vero cells point
      to its lower cytotoxicity than the sulfated galactomannan from Mimosa scabrella.

PMID- 24299870
TI  - Polyelectrolyte films based on chitosan/olive oil and reinforced with cellulose
      nanocrystals.
AB  - Composite films designed as potentially edible food packaging were prepared by
      casting film-forming emulsions based on chitosan/glycerol/olive oil containing
      dispersed cellulose nanocrystals (CNs). The combined use of cellulose
      nanoparticles and olive oil proved to be an efficient method to reduce the
      inherently high water vapor permeability of plasticized chitosan films, improving
      at the same time their tensile behavior. At the same time, it was found that the
      water solubility slightly decreased as the cellulose content increased, and
      further decreased with oil addition. Unexpectedly, opacity decreased as cellulose
      content increased, which balanced the reduced transparency due to lipid addition.
      Contact angle decreased with CN addition, but increased when olive oil was
      incorporated. Results from dynamic mechanical tests revealed that all films
      present two main relaxations that could be ascribed to the glycerol- and chitosan
      rich phases, respectively. The response of plasticized chitosan-nanocellulose
      films (without lipid addition) was also investigated, in order to facilitate the
      understanding of the effect of both additives. 

PMID- 24299871
TI  - Preparation, characterization, and thermal stability of beta-cyclodextrin/soybean
      lecithin inclusion complex.
AB  - beta-Cyclodextrin (beta-CD), which is widely used to increase the stability,
      solubility, and bioavailability of guests, can form host-guest inclusion
      complexes with a wide variety of organic molecules. In this study the beta
      CD/soybean lecithin inclusion complex was prepared. The effect of reaction
      parameters such as reaction temperature, reaction time and the molar ratio of
      beta-CD/soybean lecithin on inclusion ratio were studied. The inclusion ratio of
      the product prepared under the optimal conditions of beta-CD/soybean lecithin
      molar ratio 2:1, reaction temperature 60 degrees C reaction time 2h was 40.2%.
      The results of UV-vis, DSC, XRD and FT-IR spectrum indicated the formation of
      inclusion complex. The thermal stability experiment indicated that the thermal
      stability of soybean lecithin in inclusion complex was significantly improved
      compared with free soybean lecithin. 

PMID- 24299872
TI  - A carboxy methyl tamarind polysaccharide matrix for adhesion and growth of
      osteoclast-precursor cells.
AB  - Remodeling of bone by tissue engineering is a realistic option for treating
      several bone-related pathophysiological ailments such as osteoporosis, bone
      tumor, bone cancer or abnormal bone development. But, these possibilities are
      hindered due to lack of proper natural and biodegradable surface on which bone
      precursor cells can adhere efficiently and grow further. Here we describe the
      synthesis and characterization of a new hydrogel as an effective surface which
      can acts as a material for bone tissue engineering. This hydrogel has been
      prepared by chemically grafting a semi-synthetic polymer with a synthetic
      monomer, namely hydroxyethyl methacrylate (HEMA). Carboxy methyl tamarind (CMT)
      was selected as the semi-synthetic polymer. The hydrogel was prepared at
      different mole ratios and at the ratio of 1:10 (CMT:HEMA) yielded the best
      hydrogel as characterized by several physico-chemical analysis such as UV
      spectroscopy, FT-IR spectroscopy and swelling properties. We further demonstrate
      that this material is suitable for effective adhesion, growth and further
      clustering of bone precursor cells (RAW 264.7). This material is also compatible
      for growing other sensitive cells such as neuronal cells (Neuro2a) and human
      umbilical vein endothelial cells (HUVEC) demonstrating that this surface does not
      possess any cytotoxicity and is compatible for primary human cells too. We
      conclude that the hydrogel made of CMT:HEMA at a ratio of 1:10 can be suitable
      for bone tissue engineering and thus may have clinical as well as commercial
      application in future. 

PMID- 24299873
TI  - Functionalized bacterial cellulose derivatives and nanocomposites.
AB  - Bacterial cellulose (BC) is a fascinating and renewable natural nanomaterial
      characterized by favorable properties such as remarkable mechanical properties,
      porosity, water absorbency, moldability, biodegradability and excellent
      biological affinity. Intensive research and exploration in the past few decades
      on BC nanomaterials mainly focused on their biosynthetic process to achieve the
      low-cost preparation and application in medical, food, advanced acoustic
      diaphragms, and other fields. These investigations have led to the emergence of
      more diverse potential applications exploiting the functionality of BC
      nanomaterials. This review gives a summary of construction strategies including
      biosynthetic modification, chemical modification, and different in situ and ex
      situ patterns of functionalization for the preparation of advanced BC-based
      functional nanomaterials. The major studies being directed toward elaborate
      designs of highly functionalized material systems for many-faceted prospective
      applications. Simple biosynthetic or chemical modification on BC surface can
      improve its compatibility with different matrix and expand its utilization in
      nano-related applications. Moreover, based on the construction strategies of
      functional nanomaterial system, different guest substrates including small
      molecules, inorganic nanoparticles or nanowires, and polymers can be incorporated
      onto the surfaces of BC nanofibers to prepare various functional nanocomposites
      with outstanding properties, or significantly improved physicochemical,
      catalytic, optoelectronic, as well as magnetic properties. We focus on the
      preparation methods, formation mechanisms, and unique performances of the
      different BC derivatives or BC-based nanocomposites. The special applications of
      the advanced BC-based functional nanomaterials, such as sensors, photocatalytic
      nanomaterials, optoelectronic devices, and magnetically responsive membranes are
      also critically and comprehensively reviewed. 

PMID- 24299874
TI  - Synthesis, characterization and on field evaluation of pesticide loaded sodium
      alginate nanoparticles.
AB  - The pesticide formulations in use these days have their own burdens on farming
      systems in terms of their accumulation in soil and ecosystems which can have
      serious effects on mankind and living organisms. With the help of nanotechnology,
      controlled release of agrochemicals, site targeted delivery of various
      macromolecules desired for improved plant disease resistance, enhanced plant
      growth and efficient nutrition utilization can be easily done. Nanoencapsulation
      has an advantage of safer handling and more efficient use of pesticides with less
      exposure to environment that guarantees ecoprotection. In plant entomology,
      nanotechnology targets specific agricultural problems in plant pests interaction
      and provide new ways for crop protection. The present investigation involves the
      delivery of imidacloprid (admire) pesticide in the form of nanoformulation to
      plants and investigation of their ultimate effects which can provide some insight
      for the safe use of this novel technology for the improvement of crop yield and
      safety. 

PMID- 24299875
TI  - Milk protein-gum tragacanth mixed gels: effect of heat-treatment sequence.
AB  - The aim of this study was to investigate the role of the heat-treatment sequence
      of biopolymer mixtures as a formulation parameter on the acid-induced gelation of
      tri-polymeric systems composed of sodium caseinate (Na-caseinate), whey protein
      concentrate (WPC), and gum tragacanth (GT). This was studied by applying four
      sequences of heat treatment: (A) co-heating all three biopolymers; (B) heating
      the milk-protein dispersion and the GT dispersion separately; (C) heating the
      dispersion containing Na-caseinate and GT together and heating whey protein
      alone; and (D) co-heating whey protein with GT and heating Na-caseinate alone.
      According to small-deformation rheological measurements, the strength of the
      mixed-gel network decreased in the order: C>B>D>A samples. SEM micrographs show
      that the network of sample C is much more homogenous, coarse and dense than
      sample A, while the networks of samples B and D are of intermediate density. The
      heat-treatment sequence of the biopolymer mixtures as a formulation parameter
      thus offers an opportunity to control the microstructure and rheological
      properties of mixed gels. 

PMID- 24299876
TI  - Composition and physicochemical properties of Zedo gum exudates from Amygdalus
      scoparia.
AB  - Composition and physicochemical properties of three types of Zedo gum exudates
      from Amygdalus scoparia were investigated. Monosaccharide analysis by GC-MS
      indicated the occurrence of arabinose and galactose as the main sugars. FTIR
      spectra showed no differences in functional groups among the samples. Steady
      shear rheological data and power law parameters revealed that the white gum (W)
      was the most shear sensitive type and had the highest value of consistency
      coefficient. The mechanical spectra derived from the strain and frequency sweep
      measurements indicated a liquid viscoelastic behavior for Zedo gum dispersions.
      GPC-MALLS revealed that the white sample had the highest apparent average
      molecular weight (4.74 * 10(6)Da) and the lowest dispersity (1.045). TG-DTA
      analysis showed that the character of gum decomposition significantly depended on
      the gum type and the white sample had the highest thermal stability.

PMID- 24299877
TI  - A comprehensive study into the impact of a chitosan mouthwash upon oral
      microorganism's biofilm formation in vitro.
AB  - Modern dentistry emphasizes the importance of dental plaque control to improve
      oral health. To that end the development of oral care formulations has been
      geared toward the incorporation of antiplaque agents that may play a crucial role
      in oral health maintenance. In later years the research into antiplaque agents
      has led to the discovery of compounds with significant capability to affect
      biofilm formation. Among these compounds was chitosan, a polysaccharide which
      showed great ability to interfere with Streptococcus mutans biofilm formation. As
      such the aim of this work was to incorporate chitosan into a mouthwash matrix and
      assess its effect upon biofilm formation of oral microorganisms. This assessment
      was performed via study of the impact the mouthwash upon microbial adherence,
      biofilm formation and mature biofilms. Additionally, the action of the chitosan
      mouthwash was compared with two commercially available mouthwashes. The results
      here obtained show that only the chitosan containing mouthwash was capable of
      interfering with all microorganisms' adherence, biofilm formation and mature
      biofilms while at the same time showing vastly superior activity than both
      commercial mouthwashes assayed. As such a chitosan mouthwash shows great
      potential as a natural and efficient alternative to traditional mouthwashes. 

PMID- 24299878
TI  - Soluble chitosan-carrageenan polyelectrolyte complexes and their gastroprotective
      activity.
AB  - The soluble polyelectrolyte complexes (PEC) kappa-carrageenan (kappa-CG):chitosan
      was obtained. Binding constant value (2.11 * 10(7)mol(-1)) showed high affinity
      of kappa-CG to chitosan. The complex formation of kappa-CG:chitosan 1:10 and 10:1
      w/w was shown by centrifugation in a Percoll gradient. Using atomic force
      microscopy we showed that the supramolecular structure of the complexes is
      different from each other and from the macromolecular structure of the initial
      polysaccharides. The gastroprotective and anti-ulcerogenic effect of kappa-CG,
      chitosan and their complexes was investigated on the model of stomach ulcers
      induced by indometacin in rats. PEC kappa-CG:chitosan have gastroprotective
      properties which depend on their composition. Complex kappa-CG:chitosan 1:10 w/w
      possesses higher gastroprotective activity than the complex 10:1 w/w. These
      results suggest that the gastroprotective effect of complexes can be associated
      with their protective layer on the surface of the mucous membrane of a stomach,
      which avoids a direct contact with the ulcerogenic agent.

PMID- 24299879
TI  - Preparation of extruded polyethylene/chitosan blends compatibilized with
      polyethylene-graft-maleic anhydride.
AB  - Novel films of polyethylene and chitosan were obtained using extrusion. These
      polymers have interesting properties, and processing them with methods that are
      of high use in the industry, such as the extrusion method, can have a significant
      effect on the potential applications of these materials. The individual materials
      were thermally characterized; after this, extruded films of low density
      polyethylene and chitosan mixtures were prepared with the addition of
      polyethylene-graft-maleic anhydride as a compatibilizer for the blends, and
      glycerol, as a plasticizer for chitosan. The use of compatibilizer and
      plasticizer agents improved the processability and compatibility of the mixtures,
      as well as their mechanical properties, as revealed by mechanical property
      measurements and scanning electron microscopy. It was possible to prepare blends
      with a maximum chitosan content of 20 wt%. The material stiffness increased with
      the increase of chitosan in the sample. FTIR studies revealed the existence of an
      interaction between the compatibilizer and chitosan.

PMID- 24299880
TI  - Mannose-conjugated chitosan nanoparticles loaded with rifampicin for the
      treatment of visceral leishmaniasis.
AB  - The aim of current research work was to develop and investigate the potential of
      rifampicin (RIF) loaded mannose-conjugated chitosan nanoparticulate system for
      selective delivery to the macrophages in the management of visceral leishmaniasis
      (VL). RIF loaded mannose-conjugated chitosan nanoparticles (mCNPs) were prepared
      and characterized for shape, size, entrapment efficiency and in vitro drug
      release. The in vivo bio-distribution in albino rats and ex vivo drug uptake by
      macrophage were also evaluated. It was observed that extent of accumulation of
      mCNPs in macrophage rich organs, particularly in liver and spleen, were
      significantly higher compared to free drug. Ex vivo uptake of mCNPs was 2.31
      times higher compared to unconjugated chitosan nanoparticles (CNPs). The
      macrophage uptake of mCNPs was inhibited significantly on pre-incubation with
      0.05 M mannose in a parallel experiment, being suggestive of receptor mediated
      uptake of mannosylated nanoparticles. Our results indicate that mCNPs could be a
      promising carrier for selective delivery of RIF to macrophages for effective
      management of VL.

PMID- 24299881
TI  - Structure and properties of urea-plasticized starch films with different urea
      contents.
AB  - Films of thermoplastic starch (TPS) plasticized with different contents of urea
      were prepared by using a solution casting method. Scanning electron microscopy, X
      ray diffraction and IR spectroscopy were used to characterize structures of the
      TPS films, respectively. Water vapor sorption isotherms and tensile properties of
      the films were determined. TPS films showed more smooth and transparent in
      appearance and less B-type crystallinity than the starch film without urea. The
      effect of urea content on the structure and behavior of the TPS film could be
      divided in three stages: (1) below urea 10% where urea interacted with starch via
      H-bonding and the films showed an antiplasticization effect, (2) from urea 10% to
      30% where an apparent plasticization effect appeared on the starch because of
      free urea molecules as the effective plasticizer, and (3) a macroscopic phase
      separation occurred due to supersaturation of urea when urea content was more
      than 30%. 

PMID- 24299882
TI  - Solution blowing of chitosan/PVA hydrogel nanofiber mats.
AB  - Both nanofiber mats and hydrogel have their own advantages in wound healing. In
      this study, a novel hydrogel nanofiber mats were fabricated via solution blowing
      of chitosan and PVA solution, with various content of ethylene glycol diglycidyl
      ether (EGDE) as cross-linker. SEM observation showed that the fibers were several
      hundred nanometers in diameter with smooth surface and distributed randomly
      forming three-dimensional mats. The structure of the chitosan/PVA nanofibers was
      examined by FTIR and XPS, and the results showed that the cross-linking reaction
      occurred between EGDE and the hydroxyl groups. The mats could quickly hydrate in
      an aqueous environment to form hydrogel. Their value of equilibrate water
      absorption varied from 680 to 459% various content of EGDE. The nanofiber mats
      showed good bactericidal activity against Escherichia coli. The chitosan/PVA
      hydrogel nanofiber mats showed the combination advantages of nanofibrous mats and
      hydrogel dressing, and were suggested as potential application in wound healing. 

PMID- 24299883
TI  - Nano-biocomposite films with modified cellulose nanocrystals and synthesized
      silver nanoparticles.
AB  - Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified
      cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have
      been prepared and characterized. The functionalization of the CNC surface with an
      acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the
      PLA matrix. The positive effects of the addition of cellulose and silver on the
      PLA barrier properties were confirmed by reductions in the water permeability
      (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level
      of all nano-biocomposites in contact with food simulants were below the permitted
      limits in both non-polar and polar simulants. PLA nano-biocomposites showed a
      significant antibacterial activity influenced by the Ag content, while composting
      tests showed that the materials were visibly disintegrated after 15 days with the
      ternary systems showing the highest rate of disintegration under composting
      conditions. 

PMID- 24299884
TI  - Functional and pasting properties of pea starch and peanut protein isolate
      blends.
AB  - The functional and pasting properties of pea starch (PS) and peanut protein
      isolate (PPI) blends mixed at different proportions were studied. With the
      increasing ratio of PPI in PS/PPI blends, the solubility of the blends determined
      at 90 degrees C was increased from 16.38 to 31.28% whereas both of the water
      absorption capacity and the swelling power decreased. The pasting temperature of
      the blends increased from 72.5 to 77.5 degrees C while the peak viscosity
      decreased from 276.33 to 39.92 RVU upon the increasing level of PPI. The hardness
      of the PS/PPI blends gel decreased from 9.67 N to 0.96 N when the PPI content was
      increased from 0 to 50% in the blend. Scanning electron microscopy exhibited a
      honeycomb feature at the ratio of 90:10 and 80:20. The large fragmentary
      structure of the blending gels was formed at the ratio of 70:30 and became more
      loosed with the increased ratio of PPI in the blends.

PMID- 24299885
TI  - Ethylcellulose-coated polyolefin separators for lithium-ion batteries with
      improved safety performance.
AB  - With the widely use in portable electronic devices and electric vehicles, the
      safety of lithium-ion battery has raised serious concerns, in which the thermal
      stability of separator plays an essential role in preventing thermal runaway
      reactions. The novelty of this work is to coat commercialized polyethylene (PE)
      separator and trilayer polypropylene/polyethylene/polypropylene (PP/PE/PP)
      separator with ethylcellulose (EC), a thermally stable and renewable biomass. The
      formation of the EC layer with high porosity is through a simple dipping and
      extracting process. The effects of the EC layer on thermal shrinkage, electrolyte
      wettability and cell performance are investigated. After coating, the thermal
      shrinkage of PE separator at shutdown and meltdown point is reduced from 20% to
      9% and 42% to 23% respectively, while the drop of OCV under increasing
      temperature is also postponed from 130 degrees C to 160 degrees C. The
      electrolyte wettability of pristine trilayer PP/PE/PP separator is greatly
      improved, leading to increased capacity retention from 28% to 99% of the cell. 

PMID- 24299886
TI  - Characterizing the natural canthaxanthin/2-hydroxypropyl-beta-cyclodextrin
      inclusion complex.
AB  - A fundamental study on the phase-solubility, storage stability and antioxidant
      activity of the inclusion complex of 2-hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) with canthaxanthin (CTX) biosynthesized by Dietzia natronolimnaea HS-1 in a
      continuous bioreactor was designed. A variety of in vitro chemical methods
      including reducing power (RP), nitrite-scavenging activity (NSA), and 1,1
      diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6
      sulphonic acid (ABTS) and hydroxyl radicals scavenging capacities was used to
      determine antioxidant activities of the CTX and CTX/HP-beta-CD complex. Results
      revealed that the apparent stability constant of the inclusion complex was 669 M(
      1) in a 1:1 stoichiometric ratio. The complexation of CTX with HP-beta-CD
      significantly improved its water solubility and storage stability. An increased
      dose-dependent manner was found for the NSA and RP values of the CTX and CTX/HP
      beta-CD complex. The CTX/HP-beta-CD complex showed higher scavenging capacity
      than native CTX against DPPH, ABTS and hydroxyl radicals. It can be used as a
      promising strategy to improve the food application of CTX.

PMID- 24299887
TI  - Dehydration of dioxane by pervaporation using filled blend membranes of polyvinyl
      alcohol and sodium alginate.
AB  - Pervaporation membranes were made by solution blending of polyvinyl alcohol (PVA)
      and sodium alginate (SA). Accordingly, five different blends with PVA:SA weight
      ratio of 75:25, 50:50, 25:75, 20:80 and 10:90 designated as PS1, PS2, PS3, PS4
      and PS5, respectively, were prepared. Each of these blends was crosslinked with
      2, 4 and 6 wt% glutaraldehyde and the resulting fifteen (5 * 3) membranes were
      used for pervaporative separation of 90 wt% dioxane in water. The membranes made
      from PS4 and PS5 were not stable during pervaporation experiments. Among the
      stable membranes PS3 membrane crosslinked with 2 wt% glutaraldehyde showed the
      best results for flux and selectivity. Thus, it was filled with nano size sodium
      montmorillonite filler and used for separation of dioxane-water mixtures over the
      entire concentration range of 80-99.5 wt% dioxane in water. The membranes were
      also characterized by mechanical properties, FTIR, SEM, DTA-TGA and XRD.

PMID- 24299888
TI  - Preparation and characterization of SiO2/CMC/Ag hybrids with antibacterial
      properties.
AB  - Amorphous hybrids based on sodium salt of carboxymethyl cellulose (CMC) and
      tetraethoxysilane (TEOS) containing silver nanoparticles were prepared by sol-gel
      method. The amorphous structure, morphology and antibacterial behavior were
      clarified. The thermal stability of obtained hybrids decreased with the increase
      in silver content from 0.5 to 1.5 wt%. Infrared spectra of the material suggest
      that the main interaction between the cellulose ether and silica network is via
      hydrogen bonds (bands at approximately 3,540 and 3,625 cm(-1)). According to UV
      vis spectra the silver is present in two different states Ag(+) (absorption band
      at approximately 210 nm) and Ag(0) (band at approximately 300 nm). The different
      sizes of silver particles are present as clusters. It was demonstrated that these
      hybrids have a well pronounced antibacterial activity against B. subtilis and E.
      coli K12. Even the hybrid with 0.5 wt% Ag has efficient antibacterial activity
      for both Gram-positive and Gram-negative bacteria.

PMID- 24299889
TI  - Production of resistant starch by enzymatic debranching in legume flours.
AB  - Resistant starch (RS) was produced by enzymatic hydrolysis of flours from five
      different legumes: lentil, chickpea, faba bean, kidney bean and red kidney bean.
      Each legume was firstly treated thermally, then hydrolyzed with pullulanase for
      24h at 50 degrees C and pH 5 and lyophilized. At the end of each hydrolysis
      reaction, the RS amount ranged from 4.7% for red kidney beans to 7.5% for
      chickpeas. With respect to the curves of RS against hydrolysis time, a linear
      increase was observed initially and a plateau was generally achieved by the end
      of reaction. These curves were successfully modeled by a kinetic equation
      including three parameters: initial RS, RS at long operation time and a kinetic
      constant (k). Furthermore, the relative increase in hydrolysis, calculated using
      the kinetic parameters, was successfully correlated to the percentage of amylose.

PMID- 24299890
TI  - A new carbohydrate-based wound dressing fibre with superior absorption and
      antimicrobial potency.
AB  - Heavily exudating wounds can lead to infection and unnecessary trauma if they are
      not adequately managed. Manufacturers involved in production and marketing of
      high absorption silver dressings, besides emphasising high absorptions of their
      dressings are keen to highlight potent antimicrobial abilities of their products
      against all kinds of pathogens including MRSA. However, there are little or no
      credible reports on minimal but potent quantities of silver needed in a dressing
      to eliminate bacteria spread and growth or how effectively the silver within a
      dressing is released over time. This paper introduces a new hybrid biomaterial
      fibre made from polysaccharide-based polymers with inbuilt ability to gel and
      absorb large quantities of pseudo exudates. Furthermore, it will be reported that
      the new fibre carries up to six times less silver than it is conventionally used
      in silver dressings and displays a very slow rate of release whilst maintaining
      full potency over time against known Gram positive, Gram negative micro-organisms
      including MRSA. The paper concludes that the developed hybrid fibre has long
      lasting antimicrobial and gelling properties comparable, if not better, than
      Acticoat AA and Aquacel Ag, two commercially available silver dressings. 

PMID- 24299891
TI  - Structure and thermal property of alkaline hemicelluloses from steam exploded
      Phyllostachys pubescens.
AB  - An environmentally friendly pretreatment process was developed to fractionate
      hemicelluloses from dried and water-immersed Phyllostachys pubescens chips by
      steam explosion followed with alkali and alkali/ethanol extractions. The detailed
      chemical and structural features of the isolated hemicellulosic fractions were
      comparatively investigated by HPAEC, GPC, FT-IR, (13)C NMR spectroscopies, and
      TGA analysis. It was found that the xylose/arabinose ratios of hemicelluloses
      obtained from alkali and alkali/ethanol extractions were 21.5-34.4 and 7.7-9.9,
      respectively, suggesting that hemicelluloses extracted with alkali had relatively
      lower degree of branches than those extracted with alkali/ethanol. Hemicellulosic
      fractions isolated from the water-immersed samples were obtained in high yields
      and exhibited similar compositions, which can be used as raw materials for
      production of value-added products. Furthermore, the hemicelluloses extracted
      with alkali had relatively higher molecular weight than those extracted with
      alkali/ethanol. In addition, an increment of incubation time resulted in a
      decreased thermal stability of hemicelluloses obtained from water-immersed
      sample. 

PMID- 24299892
TI  - The influence of substituted phenols on the sol:gel transition of hydroxypropyl
      methylcellulose (HPMC) aqueous solutions.
AB  - The influence of the physicochemical parameters of substituted aromatic molecules
      on the phase transition from sol to gel of hydroxypropyl methylcellulose (HPMC)
      has been investigated using a homologous series of substituted phenols. Using a
      turbimetric methodology, concentration dependent suppression of phase transition
      temperature of HPMC was observed for phenol and its derivatives, including methyl
      , nitro- and chloro-substituted molecules. Although no strong direct relationship
      between single molecular physicochemical properties of the phenolic compounds
      (such as pKa, LogP and other molecular descriptors) and DeltaCPT was found for
      the compounds tested, a successful prediction of behaviour could be obtained by
      using a combination of parameters. This suggested that the interaction mechanism
      between HPMC and the substituted aromatic moiety is a complex summation of the
      different molecular physicochemical properties. Identification of these
      potentially deleterious chemical moieties may be of value in a pharmaceutical
      context when considering preformulation of drug structures containing them. An
      incompatibility between drug and polymer may be indicative of deleterious effects
      resulting from formulation with hydrophilic matrix dosage forms containing
      cellulose ethers such as HPMC. 

PMID- 24299893
TI  - Descriptive parameters for revealing substitution patterns of sugar beet pectins
      using pectolytic enzymes.
AB  - Enzymatic fingerprinting was applied to sugar beet pectins (SBPs) modified by
      either plant or fungal pectin methyl esterases and alkali catalyzed de
      esterification to reveal the ester distributions over the pectin backbone. A
      simultaneous pectin lyase (PL) treatment to the commonly used endo
      polygalacturonase (endo-PG) degradation showed to be effective in degrading both
      high and low methylesterified and/or acetylated homogalaturonan regions of SBP
      simultaneously. Using LC-HILIC-MS/ELSD, we studied in detail all the diagnostic
      oligomers present, enabling us to discriminate between differently prepared sugar
      beet pectins having various levels of methylesterification and acetylation.
      Furthermore, distinction between commercially extracted and de-esterified sugar
      beet pectin having different patterns of substitution was achieved by using novel
      descriptive pectin parameters. In addition to DBabs approach for
      nonmethylesterified sequences degradable by endo-PG, the "degree of hydrolysis"
      (DHPG) representing all partially saturated methylesterified and/or acetylated
      galacturonic acid (GalA) moieties was introduced as a new parameter.
      Consequently, the description DHPL has been introduced to quantify all esterified
      unsaturated GalA oligomers. 

PMID- 24299894
TI  - In situ forming antibacterial dextran blend hydrogel for wound dressing: SAA
      technology vs. spray drying.
AB  - This study focuses on designing microparticulate carriers based on high
      mannuronic alginate and amidated pectin blend loaded with gentamicin sulphate
      able to move rapidly from dry to soft hydrogel. Supercritical assisted
      atomization was used to produce microparticles in form of dry powder and
      characteristics were compared with those obtained by spray-drying. Particles with
      very high encapsulation efficiency (approximately 100%) and small diameter (less
      than 2 MUm) showed good flowability and high fluid uptake enabling wound site
      filling and limiting bacterial proliferation. Moisture transmission of the in
      situ formed hydrogel was about 95 g/m(2)h, ideal to avoid wound dehydration or
      occlusion phenomena. All formulations presented a burst effect, suitable to
      prevent infection spreading at the beginning of the therapy, followed by
      prolonged release (4-10 days) related to drug/polymers ratio. Antimicrobial tests
      showed stronger effect than pure GS over time (up-to 24 days) and the ability to
      degrade preformed biofilms, essential to properly treat infected wounds.

PMID- 24299895
TI  - Dextran sulfate-coated superparamagnetic iron oxide nanoparticles as a contrast
      agent for atherosclerosis imaging.
AB  - The hallmark of atherosclerosis in its early pathogenic process is the
      overexpression of class A scavenger receptors (SR-A) by activated macrophages. In
      this study, dextran sulfate-coated superparamagnetic iron oxide nanoparticles (DS
      SPIONs), as a magnetic resonance (MR) imaging contrast agent of atherosclerosis,
      was prepared via the facile co-precipitation method using a versatile double
      hydrophilic block copolymer comprising of a DS segment (ligand for SR-A) and a
      poly(glyclerol methacrylate) segment (SPIONs surface-anchoring unit). The
      physicochemical properties of the DS-SPIONs were investigated using various
      instruments. DS-SPIONs exhibited high aqueous stability compared to dextran
      coated SPIONs (Dex-SPIONs), which were used as controls. The cellular uptake
      behaviors of DS-SPIONs and Dex-SPIONs were evaluated using Prussian blue assay.
      Interestingly, the DS-SPIONs were effectively taken up by activated macrophages
      compared to Dex-SPIONs. However, the cellular uptake of DS-SPIONs by activated
      macrophages was remarkably reduced in the presence of free DS. These results
      suggest that activated macrophages internalize DS-SPIONs via receptor (SR-A)
      mediated endocytosis. T2-weighted MR imaging of the cells demonstrated that
      activated macrophages treated with DS-SPIONs showed a significantly lower signal
      intensity compared to those treated with Dex-SPIONs. Overall, these results
      suggest that DS-SPIONs may be utilized as a potential contrast agent for
      atherosclerosis MR imaging. 

PMID- 24299896
TI  - Formulation and in vitro evaluation of xanthan gum-based bilayered mucoadhesive
      buccal patches of zolmitriptan.
AB  - A novel bilayered mucoadhesive buccal patch of zolmitriptan was prepared using
      xanthan gum (XG) as mucoadhesive polymer. Hydroxypropyl methylcellulose E-15 was
      used as film-former and polyvinyl alcohol (PVA) was incorporated, to increase the
      tensile strength of the patches. To study the effect of independent variables
      viz. concentrations of XG and PVA, on various dependent variables like in vitro
      drug release, ex vivo mucoadhesive strength and swelling index, 3(2) factorial
      design was employed. In vitro drug release studies of optimized formulation
      showed initially, rapid drug release; 43.15% within 15 min, followed by sustained
      release profile over 5h. Incorporation of 4% dimethyl sulfoxide enhanced drug
      permeability by 3.29 folds, transported 29.10% of drug after 5h and showed no
      buccal mucosal damage after histopathological studies. In conclusion, XG can be
      used as a potential drug release modifier and mucoadhesive polymer for successful
      formulation of zolmitriptan buccal patches.

PMID- 24299897
TI  - Gamma irradiation of cotton fabrics in AgNO3 solution for preparation of
      antibacterial fabrics.
AB  - Silver nanoparticles (AgNPs) with diameter about 12 nm were immobilized on the
      surface of cotton fabrics by gamma-irradiation of fabrics in the AgNO3 chitosan
      solution. Effects of absorbed dose, concentration of AgNO3 solution on
      immobilization of the AgNPs on fabrics were investigated. The optimal dose was
      selected to be 13.8 kGy and the suitable concentration of AgNO3 was 1.5mM in 1%
      chitosan solution. The content of AgNPs on fabrics was of 1,696 +/- 80 mg/kg for
      these conditions. The presence of AgNPs on fabrics was confirmed from scanning
      electron microscopy (SEM) images and X ray diffraction (XRD) patterns. The
      antibacterial activity of AgNPs/cotton fabrics after 40 washings against
      Staphylococcus aureus and Escherichia coli was found to be 99.99%. In addition,
      the AgNPs fabrics were innoxious to the skin (k=0) after 1, 5, 10, 20, 30 and 40
      washings by skin-irritation testing to animal (rabbit).

PMID- 24299898
TI  - Deterioration of ancient Korean paper (Hanji), treated with beeswax: a
      mechanistic study.
AB  - In the early 15th century, beeswax coating was applied to some of the cellulosic
      documents in a futile attempt to better conserve the paper. However, this
      treatment caused much more severe degradation compared to untreated Hanji. In the
      current study, the degradation pathway of this beeswax-treated Hanji has been
      clarified for the first time. The degradation of cellulose was investigated by
      labeling of oxidized groups combined with gel permeation chromatography,
      providing profiles of carbonyl and carboxyl groups relative to the molar mass
      distribution. The beeswax caused purely hydrolytic damage, leading to a decrease
      in molar mass to about one fifth of the original value. Oxidative degradation, by
      contrast, did not occur to any significant extent. Hydrolysis was not caused by
      acids but by microorganism feeding on the beeswax and excreting cellulolytic
      enzymes, which cause similar cellulose damage patterns. The hydrolytic enzymes
      were identified by typical metabolites present in the Hanji. 

PMID- 24299899
TI  - Gum ghatti and Fe3O4 magnetic nanoparticles based nanocomposites for the
      effective adsorption of rhodamine B.
AB  - This article reports the development of a new nanocomposite using gum ghatti
      crosslinked with poly(acrylic acid-co-acrylamide) reinforced with iron oxide
      magnetic nanoparticles. The nanocomposite was characterized through BET, FT-IR,
      XRD, SEM-EDX, TGA and TEM and applied for the removal of RhB. Different optimized
      adsorption parameters were adsorbent dose (0.8 g/L) and pH (7.0). The adsorption
      isotherm data was used to study Langmuir, Freundlich and Dubinin-Kaganer
      Radushkevich isotherm models. The value of correlation coefficient confirmed the
      applicability of Langmuir isotherm model with maximum adsorption efficiency of
      654.87 mg/g. The adsorption kinetics data showed pseudo second order reaction.
      Thermodynamic studies showed that the adsorption process was endothermic and
      spontaneous. Moreover, the adsorbent was successfully utilized for successive
      three cycles for the adsorption-desorption of RhB.

PMID- 24299900
TI  - A single-fly assay for foraging behavior in Drosophila.
AB  - For many animals, hunger promotes changes in the olfactory system in a manner
      that facilitates the search for appropriate food sources. In this video article,
      we describe an automated assay to measure the effect of hunger or satiety on
      olfactory dependent food search behavior in the adult fruit fly Drosophila
      melanogaster. In a light-tight box illuminated by red light that is invisible to
      fruit flies, a camera linked to custom data acquisition software monitors the
      position of six flies simultaneously. Each fly is confined to walk in individual
      arenas containing a food odor at the center. The testing arenas rest on a porous
      floor that functions to prevent odor accumulation. Latency to locate the odor
      source, a metric that reflects olfactory sensitivity under different
      physiological states, is determined by software analysis. Here, we discuss the
      critical mechanics of running this behavioral paradigm and cover specific issues
      regarding fly loading, odor contamination, assay temperature, data quality, and
      statistical analysis. 

PMID- 24299901
TI  - Complex visual hallucinations as the sole manifestation of symptomatic temporo
      occipital lobe epilepsy due to old intracerebral hemorrhage.

PMID- 24299902
TI  - Partial lipectomy reduces dimethylhydrazine-induced carcinogenic initiation in
      the colon of rats.
AB  - This study investigated whether visceral adipose tissue directly modulates the
      development of preneoplastic lesions in the colon of carcinogen-treated rats.
      Wistar rats (n=64) were randomly assigned to 8 experimental groups in two
      experiments. In one experiment, 32 rats were exposed or not to either carcinogen
      treatment (dimethylhydrazine, DMH; 125 mg/kg) or high-fat diet (standard chow
      enriched with 14% lard) or both for 56 days. In a second experiment, 32 rats were
      exposed to a carcinogen or they underwent partial lipectomy or both for 30 days
      (partial lipectomy groups underwent ablation of mesenteric and parametrial fat
      pads, whereas sham groups did not; all rats were fed with standard chow). Colon
      was collected for histopathological analysis. After 56 experimental days a high
      fat diet increased carcinogenic mutations in the colonic epithelia. Partial
      lipectomy reduced weight gain in carcinogen-exposed rats and decreased the de
      novo formation of mesenteric and parametrial fat pads. Partial lipectomy
      significantly inhibited the mutational process after 30 days: there were fewer
      colonic preneoplastic lesions and less proliferation, apoptosis, and
      inflammation. These data suggest that visceral adipose tissue promotes colon
      carcinogenesis and enhances the establishment and expansion of genetically
      mutated cells in colonic epithelia.

PMID- 24299903
TI  - The risk of rinderpest re-introduction in post-eradication era.
AB  - In 2011, ten years after the last reported outbreak, the eradication of
      rinderpest was declared. However, as rinderpest virus stocks still exist, there
      remains a risk of rinderpest re-introduction. A semi-quantitative risk assessment
      was conducted to assess this risk, which was defined as the probability of at
      least one host becoming infected and infectious outside a laboratory anywhere in
      the world within a one-year period. Pathways leading to rinderpest re
      introduction were: deliberate or accidental use of virus in laboratories,
      deliberate or accidental use of vaccines, host exposure to an environmental
      source of virus, and use of virus for anti-animal biological warfare. The
      probability of each pathway step occurring was estimated through expert opinion
      elicitation. The risk estimate was associated with a high degree of uncertainty.
      It was estimated to range from negligible to high, with the median being very
      low. The accidental use of laboratory virus stocks was the highest risk pathway.
      Reducing the number of virus stocks and restricting their use, as well as
      upgrading the laboratories to a higher biosafety level, would effectively
      decrease the maximum and median risks. Likewise, ensuring that remaining vaccine
      stocks are not used and are instead destroyed or relocated to a limited number of
      regional repositories would also have a major effect on these estimates. However,
      these measures are unlikely to eliminate the risk of rinderpest re-introduction
      so that maintaining response preparedness is essential. 

PMID- 24299904
TI  - The application of medical informatics to the veterinary management programs at
      companion animal practices in Alberta, Canada: a case study.
AB  - Companion animals closely share their domestic environment with people and have
      the potential to, act as sources of zoonotic diseases. They also have the
      potential to be sentinels of infectious and noninfectious, diseases. With the
      exception of rabies, there has been minimal ongoing surveillance of, companion
      animals in Canada. We developed customized data extraction software, the
      University of, Calgary Data Extraction Program (UCDEP), to automatically extract
      and warehouse the electronic, medical records (EMR) from participating private
      veterinary practices to make them available for, disease surveillance and
      knowledge creation for evidence-based practice. It was not possible to build,
      generic data extraction software; the UCDEP required customization to meet the
      specific software, capabilities of the veterinary practices. The UCDEP, tailored
      to the participating veterinary practices', management software, was capable of
      extracting data from the EMR with greater than 99%, completeness and accuracy.
      The experiences of the people developing and using the UCDEP and the, quality of
      the extracted data were evaluated. The electronic medical record data stored in
      the data, warehouse may be a valuable resource for surveillance and evidence
      based medical research. 

PMID- 24299905
TI  - Farm-level risk factors for the occurrence, new infection or persistence of
      tuberculosis in cattle herds from South-Central Spain.
AB  - Eradication of tuberculosis (TB) in cattle is a priority in the EU. However, and
      despite the resources invested, TB eradication is still a goal yet to be
      accomplished. As a consequence, the identification of risk factors contributing
      to TB transmission and persistence is key to a better understand and, ultimately,
      more cost-effectively control and eradicate this complex zoonotic disease
      worldwide. This study aimed to identify the factors contributing to the TB
      occurrence, new infection, and persistence in one of the most TB-prevalent
      regions in the South-Central part of Spain (SCS), Ciudad Real (CR), and for which
      high quality and detailed information on cattle and wild ungulate demographics,
      management, and sanitary status was available for up to 5 years (2007-2011).
      Multilevel logistic modeling was used for this purpose. Results of this study
      revealed that the risk for TB (occurrence, new infection, and/or persistence) in
      cattle herds from CR is related to TB-persistence on farm in previous years,
      extensive production systems (beef and bullfighting being more risky that dairy)
      and large farm in terms of cattle number. Also, the presence and proximity of
      fenced hunting estates (which are usually intensively managed) significantly
      contributed to the risk of TB occurrence and persistence in CR. This association
      suggests that wild ungulates may play a role as TB-reservoirs and transmit TB to
      cattle in the CR, a region where TB is endemic and is associated with extensive
      farming of beef cattle. To the best of author's knowledge this is the first study
      to (i) evaluate the wild ungulate-domestic interface at a farm level using
      detailed information over an extensive region and period of time (2007-2011) and
      (ii) to identify a direct association between TB in cattle and the proximity and
      management practices of wild ungulates. Methods and results presented here may
      support policies to better prevent and control TB in the SCS and in other
      regions/countries with similar epidemiological conditions. 

PMID- 24299906
TI  - Effects of indirect exposure of mice pups to endosulfan via their dams during
      gestation and lactation periods and the ameliorative effect of vitamin E.
AB  - During gestation and lactation, the experimental mice dams received one of the
      following treatments: (a) diet free of pesticide; (b) diet enriched with
      endosulfan (END); 30.0 ug kg(-1); (c) diet free of pesticide + oral vitamin E
      (alpha-tocopherol; 200 mg kg(-1) per mouse); and (d) diet enriched with END (30.0
      ug kg(-1)) + oral vitamin E (200 mg kg(-1) per mouse). At weaning, pups and dams
      were killed, and selected organs as well as blood samples were collected for
      analyses. Compared with the control results, END induced alteration in a number
      of biochemical and histopathological parameters either in the dams or their
      offspring. The ameliorative effect of vitamin E to superoxide dismutase based on
      the "ameliorative index (AI)" for mothers and pups was 0.84 and 0.72,
      respectively. The AI for malondialdehyde reached a maximum value of nearly equal
      to 1.0 for dams or pups. For butyryl cholinesterase, the AI was 0.90 and 0.94 for
      dams and pups, respectively. In conclusion, a dietary exposure during gestation
      and lactation to low dose of END caused significant changes in the mother but
      also in the weaned animals that had not been directly exposed to this pesticide.
      These biological and histological alterations could be reversed to a great extent
      by oral supplementation of vitamin E. 

PMID- 24299907
TI  - Female gender as a susceptibility factor for drug-induced liver injury.
AB  - Adverse drug reactions (ADRs) can involve all tissues and organs, but liver
      injuries are considered among the most serious. A number of prospective,
      multicenter studies have confirmed a higher risk of ADRs in general among female
      subjects compared to a male cohort. Although drug-induced liver injury (DILI) is
      infrequently encountered, the preponderance of evidence suggests that women
      appear to be more susceptible than men to fulminate hepatic/acute liver failure
      especially in response to some anti-infective drugs and to autoimmune-like
      hepatitis following exposure to certain other therapeutic drugs. A number of
      hypotheses have been proposed to explain this sex difference in susceptibility to
      DILI. Collectively, these hypotheses suggest three basic sex-dependent mechanisms
      that include differences in various aspects of drug pharmacokinetics (PK) or
      pharmacodynamics following the administration of certain drugs; specific hormonal
      effects or interactions with immunomodulating agents or signaling molecules; and
      differences in the adverse response of the immune system to some drugs, reactive
      drug metabolites, or drug-protein adducts. At the preclinical drug safety stage,
      there is a need for more research on hormonal effects on drug PK and for
      additional research on gender differences in aberrant immune responses that may
      lead to idiosyncratic DILI in some female patients. Because the detection of rare
      but serious hepatic ADRs requires the exposure of very large patient populations,
      pharmacovigilance networks will continue to play a key role in the postmarketing
      surveillance for their detection and reporting. 

PMID- 24299908
TI  - Detection and neutralization of cobra venom using rabbit antiserum in
      experimental envenomated mice.
AB  - A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the
      venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs,
      liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after
      cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h
      intervals up to 24 h). Whole venom antiserum or individual venom protein
      antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by
      Western blotting and ELISA, and antibody titer was also assayed by ELISA.
      Antiserum raised against cobra venom in rabbit significantly neutralized the
      toxicity of venom-injected mice at different time intervals after treatment. The
      assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate,
      and the venom was detected up to 24 h after venom injection. Venom was detected
      in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and
      blood. As observed in mice, tissue at the site of bite area showed the highest
      concentration of venom and the brain showed the least. Moderate amounts of venoms
      were found in liver, spleen, kidneys, heart, and lungs. Development of a simple,
      rapid, and species-specific diagnostic kit based on this ELISA technique useful
      to clinicians is discussed. 

PMID- 24299909
TI  - Immunogenic activity of the fish tapeworm Pterobothrium heteracanthum
      (Trypanorhyncha: Pterobothriidae) in BALB/c mice.
AB  - The aim of this study was to verify the immunogenicity of Pterobothrium
      heteracanthum (Cestoda: Trypanorhyncha) crude protein extract (PH-CPE) in BALB/c
      mice. The parasites were obtained from Micropogonias furnieri (Osteichthyes:
      Sciaenidae). Groups of six mice were each immunized with 10, 50 or 100 MUg of PH
      CPE, on days 0 and 35. Both specific IgG and IgE responses were developed after
      immunization. The immunoblot assay revealed that specific IgG recognizes PH-CPE
      proteins with two molecular weight ranges, 60-75 and 30-40 kDa, and that IgE
      recognizes larger proteins over 120 kDa. This appears to be the first report on
      the immunogenicity of metacestodes within the Pterobothriidae and that PH-CPE is
      a potential inducer of a specific IgE response. 

PMID- 24299910
TI  - Hip problems in cerebral palsy: screening, diagnosis and treatment.
AB  - PURPOSE OF REVIEW: Spastic type is the most common form of cerebral palsy. The
      purpose of this review was to evaluate recent literature for current trends in
      the surveillance and treatment of spastic hip problems in cerebral palsy. RECENT
      FINDINGS: Cerebral palsy is still the most common physical disability in
      childhood in developed countries. Surveillance programs have had promising
      results in the detection of 'at risk' patients. However, neither regular
      radiographic screening nor surgical treatment indications and procedures have
      shown any progression in the last decade. In addition, recent studies have
      focused heavily on nonoperative treatment strategies to improve gait. SUMMARY:
      Cerebral palsy is a static encephalopathy causing myostatic contractures
      especially in the knee and hip. Unbalanced hip contractures can lead to silent
      hip dislocation. Surgical and rehabilitative approaches such as soft tissue
      lengthening and proximal femoral and pelvic osteotomies can help patients
      maintain function and comfort. Selective dorsal rhizotomy or Intrathecal Baclofen
      Pump insertion or, recently, noninvasive techniques such as neurodevelopmental
      therapy may help patients and caregivers cope with what is still a devastating
      and inexorably progressive disorder.

PMID- 24299912
TI  - Introduction and overview to issue on new developments in pediatric
      hematology/oncology.

PMID- 24299911
TI  - Old and new approaches to diagnosing and treating latent tuberculosis in children
      in low-incidence countries.
AB  - PURPOSE OF REVIEW: The primary purpose is to review guidance on the testing and
      treatment of latent tuberculosis infection (LTBI) in children. Most children and
      adults with LTBI have positive tuberculin skin test (TST) or interferon gamma
      release assay (IGRA) results, normal examinations, and normal chest radiographs.
      Diagnosis of and treatment completion for LTBI are critical to diminish future
      cases of tuberculosis (TB) disease. RECENT FINDINGS: Children should be screened
      for TB risk factors, and only children with risk factors should be tested with
      either a TST or an IGRA. IGRAs measure interferon gamma production by lymphocytes
      after they are stimulated ex vivo by antigens that are primarily Mycobacterium
      tuberculosis-specific. The foundation of LTBI therapy in the United States has
      been 9 months of daily isoniazid, but shorter treatment regimens now exist,
      including a 12-dose regimen of weekly isoniazid and rifapentine. These shorter
      regimens are associated with higher completion rates. SUMMARY: There are two
      distinct modalities for LTBI diagnosis and several treatment regimens that can
      prevent TB disease in infected children. The selection of treatment regimen
      should take several factors into consideration, including adherence, drug
      susceptibility results of the presumed source case (if known), safety, cost, and
      patient preference.

PMID- 24299913
TI  - High-throughput fluorometric measurement of potential soil extracellular enzyme
      activities.
AB  - Microbes in soils and other environments produce extracellular enzymes to
      depolymerize and hydrolyze organic macromolecules so that they can be assimilated
      for energy and nutrients. Measuring soil microbial enzyme activity is crucial in
      understanding soil ecosystem functional dynamics. The general concept of the
      fluorescence enzyme assay is that synthetic C-, N-, or P-rich substrates bound
      with a fluorescent dye are added to soil samples. When intact, the labeled
      substrates do not fluoresce. Enzyme activity is measured as the increase in
      fluorescence as the fluorescent dyes are cleaved from their substrates, which
      allows them to fluoresce. Enzyme measurements can be expressed in units of
      molarity or activity. To perform this assay, soil slurries are prepared by
      combining soil with a pH buffer. The pH buffer (typically a 50 mM sodium acetate
      or 50 mM Tris buffer), is chosen for the buffer's particular acid dissociation
      constant (pKa) to best match the soil sample pH. The soil slurries are inoculated
      with a nonlimiting amount of fluorescently labeled (i.e. C-, N-, or P-rich)
      substrate. Using soil slurries in the assay serves to minimize limitations on
      enzyme and substrate diffusion. Therefore, this assay controls for differences in
      substrate limitation, diffusion rates, and soil pH conditions; thus detecting
      potential enzyme activity rates as a function of the difference in enzyme
      concentrations (per sample). Fluorescence enzyme assays are typically more
      sensitive than spectrophotometric (i.e. colorimetric) assays, but can suffer from
      interference caused by impurities and the instability of many fluorescent
      compounds when exposed to light; so caution is required when handling fluorescent
      substrates. Likewise, this method only assesses potential enzyme activities under
      laboratory conditions when substrates are not limiting. Caution should be used
      when interpreting the data representing cross-site comparisons with differing
      temperatures or soil types, as in situ soil type and temperature can influence
      enzyme kinetics. 

PMID- 24299914
TI  - Blood pressure measurements are unreliable to diagnose hypertension in primary
      care.
AB  - OBJECTIVES: To evaluate the accuracy of blood pressure (BP) measurements
      performed by primary care physicians (PCPs), and to assess whether it improves
      following a short theoretical training. METHODS: Observational study in 26
      primary care practices in Geneva, Switzerland. The PCPs were asked to measure BP
      on 10 volunteers, within the usual context of their practice. Two trained
      research assistants repeated the measures immediately after the PCPs. The PCPs
      were then randomized to receive detailed training documentation on standardized
      BP measurement (group I: 14 doctors) or information about high BP (group II: 12
      doctors). Measures were repeated a few weeks later. We computed accuracy and
      diagnostic categorization of high BP comparing the PCPs' measurements to the
      average value of four measurements by the research assistants (gold standard). T
      tests were used to compare measurements between the two educational groups, both
      at baseline and following exposure to the educational material. RESULTS: BP
      measurements were performed on 257 volunteers at baseline and 251 after training.
      At baseline, the mean BP difference between PCPs and the gold standard were 23.0
      mmHg (21.3-24.6) for systolic and 15.3 mmHg (14.3-16.3) for DBP. Following
      training, the mean difference remained high [group I: 22.3 mmHg (20.4-24.2) and
      14.4 mmHg (12.6-16.2); group II: 25.3 mmHg (22.7-27.9) and 17.0 mmHg (15.3
      18.7)]. As a result, 24-32% volunteers were misdiagnosed as having systolic
      hypertension and 15-21% as having diastolic hypertension. CONCLUSION: Though
      widely used in the assessment of hypertension in ambulatory settings, in-office
      BP measurements are highly inaccurate, even following training.

PMID- 24299915
TI  - Predictors and outcomes of resistant hypertension among patients with coronary
      artery disease and hypertension.
AB  - OBJECTIVE: Resistant hypertension (res-HTN) is a challenging problem, but little
      is known of res-HTN in patients with coronary artery disease (CAD). In this post
      hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed
      prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with
      hypertension. METHODS: Participants (n=17190) were divided into three groups
      according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three
      or fewer drugs); uncontrolled (BP >= 40/90 mmHg on two or fewer drugs); or
      resistant (BP >= 40/90 mmHg on three drugs or any patient on at least four
      drugs). RESULTS: The prevalence of res-HTN was 38%: significant predictors of res
      HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race
      (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had
      multivariate-adjusted association with higher risk of adverse outcomes {first
      occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke
      [hazard ratio 1.27, 95% confidence interval (CI) 1.13-1.43], and individual
      outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13-1.48), cardiovascular
      mortality (hazard ratio 1.47, 95% CI 1.21-1.78), and nonfatal stroke (hazard
      ratio 1.61, 95% CI 1.17-2.22), but not nonfatal myocardial infarction (hazard
      ratio 0.98, 95% CI 0.72-1.34)}. Adverse outcomes, except nonfatal stroke, did not
      differ in patients with res-HTN compared to uncontrolled HTN. CONCLUSIONS: Res
      HTN is common in patients with CAD and hypertension, associated with poor
      prognosis, and linked with a number of conditions. Emphasis should be placed on
      recognizing those at risk for res-HTN and future studies should examine whether
      more aggressive treatment of res-HTN improves outcomes.

PMID- 24299916
TI  - Target organ damage among hypertensive adults in rural Nigeria: a cross-sectional
      study.
AB  - OBJECTIVES: To study the prevalence of target organ damage (TOD) in hypertensive
      adults in a general population in rural Nigeria, to assess determinants of TOD
      and the contribution of TOD screening to assess eligibility for antihypertensive
      treatment. METHODS: All adults diagnosed with hypertension (n=387) and a random
      sample (n=540) out of all nonhypertensive adults, classified during a household
      survey in 2009, had a blood pressure measurement and were invited for TOD
      (myocardial infarction, left ventricular hypertrophy, angina pectoris, kidney
      disease) screening in 2011. RESULTS: Participation in TOD screening was 51%
      (n=196) in respondents with hypertension and 33% (n=179) in those without
      hypertension. TOD prevalence in hypertensive and nonhypertensive adults was 32
      and 15%, respectively. Hypertension severity was a strong determinant for TOD
      [grade 1 odds ratio (OR) 2.66, 95% confidence interval (CI)1.04-6.84; grade 2 OR
      3.82, 95% CI 1.41-10.36]. Out of 196 hypertensive patients, 151 were untreated,
      of whom all grade 2 hypertensive patients (n=71) were eligible for treatment.
      Screening revealed TOD in 19 out of 80 grade 1 hypertensive respondents (24%),
      therefore also classifying them as eligible for treatment. TOD screening
      hypertensive nonrespondents had more severe hypertension than hypertensive
      respondents, which may have resulted in an underestimation of the true prevalence
      of TOD among adults with hypertension. CONCLUSION: A high prevalence of 32% TOD
      in hypertensive adults in rural Nigeria was observed. Almost a quarter of
      respondents with grade 1 hypertension were eligible for antihypertensive
      treatment based on TOD screening findings. As TOD screening is mostly unavailable
      in sub-Saharan Africa, we propose antihypertensive treatment for all patients
      with hypertension.

PMID- 24299917
TI  - Pretreatment with sevoflurane attenuates direct lung injury.
AB  - BACKGROUND: Sevoflurane exerts effects on pulmonary cells that could protect
      against lung injury. We evaluated the potential of pretreatment with sevoflurane
      to attenuate lipopolysaccharide (LPS)-induced lung injury. METHODS: LPS was
      administered intratracheally in Wistar rats to induce lung injury. Sevoflurane
      was administered for 30 min at 0.25, 0.5 or 1.0 MAC 15 min before LPS or for 30
      min at 0.5 MAC 24 hours before LPS. After initial analysis of bronchoalveolar
      lavage fluid (BALF) cells and total protein, the group of 0.5 MAC 15 min before
      LPS was further analyzed for surfactant aggregates subfractions, plasma
      malondialdehyde levels and lung histology. RESULTS: LPS instillation resulted in
      neutrophils sequestration in the lungs, loss of alveolar macrophages, increased
      BALF total protein and decreased large surfactant aggregates. Only inhalation of
      sevoflurane for 30 min at 0.5 MAC 15 min before LPS installation effectively
      reduced neutrophil accumulation, preserved alveolar epithelial cells and reduced
      total protein content in BALF. This regimen also reduced plasma malondialdehyde
      levels and increased large surfactant aggregates, despite the application of
      mechanical ventilation. This effect was preserved after LPS instillation and the
      favorable composition of surfactant was maintained. CONCLUSION: Pretreatment with
      sevoflurane effectively attenuates direct severe lung injury, possibly by
      inhibition of neutrophil accumulation and alteration of the surfactant
      composition.

PMID- 24299918
TI  - Doppler study of the effects of inhaled nitric oxide and intravenous almitrine on
      regional pulmonary blood flows in patients with acute lung injury.
AB  - BACKGROUND: Lung ultrasound can be used at bedside to assess initial lung
      morphology in hypoxemic patients. We hypothesized that blood flow in consolidated
      lung and therefore effects of inhaled nitric oxide (iNO) and intravenous
      almitrine could be directly assessed using Doppler transesophageal
      echocardiography (TEE). METHODS: We conducted a prospective study including 13
      ALI patients with consolidated left lower lobe (LLL). Regional arterial and
      venous flow signals within the consolidation were recorded with TEE using Doppler
      at baseline, after iNO (5 ppm), almitrine (4 MUg/kg/min) and their combination.
      Pulmonary shunt (Qs/Qt) was measured using a Swan-Ganz catheter. Arterial and
      venous velocity time integral (VTI), peak velocity (Vmax) and mean velocity
      (Vmean) were measured. Patients were responders if PaO2 basal value increased by
      20% after iNO or almitrine. RESULTS: In 7 NO responders, iNO decreased regional
      arterial VTI (8.1+/-1.9 vs. 6.7+/-1.6, P<0.05). In 8 almitrine responders,
      almitrine decreased regional arterial and venous VTI (from 6.7+/-2.0 to 4.5+/-2.3
      cm and from 12.3+/-5.4 to 7.5+/-3.8 cm, respectively, P<0.05). For all patients,
      combination of iNO and almitrine decreased regional arterial and venous VTI (from
      7.3+/-0.3 to 4.1+/-0.3 cm and from 12.6+/-0.7 to 6.7+/-0.8 cm, respectively,
      P<0.05). Arterial and venous Vmean and Vmax significantly decreased. Variations
      of arterial VTI and venous Vmean were correlated to variations of Qs/Qt (r=.71,
      P<.001 and r=.62, P<.01, respectively). CONCLUSION: Doppler of consolidated LLL
      allows assessment of regional pulmonary circulation in ICU settings. It detects
      changes in flow profiles resulting from the administration of NO and/or
      almitrine. Further applicability remains to be determined.

PMID- 24299919
TI  - Inconsistent size nomenclature in extraglottic airway devices.
AB  - BACKGROUND: Extraglottic airway devices (EADs) are frequently used airway
      devices, yet often they seal poorly, resulting in a functionally unacceptable
      leak. Optimal size selection of the EAD is therefore critical to the safe and
      effective use of an EAD. This review is designed to delineate the sizing
      recommendations of EADs and indicate the differences in order to make the optimal
      choice for device effectiveness and patient safety. METHODS: We searched
      manufacturing' guidelines regarding size recommendations of EADs. Alternative
      size selection suggestions were obtained through an extensive literature search.
      RESULTS: Most manufacturers offer different types and a wide range of (up to 8
      different) sizes of EADs. Size ranges offered by manufacturers are most often
      based on weight, although some manufacturers offer alternative EADs based on a
      variety of patient variables (age, gender, height). Even 'one-size-fits-all'
      adult EADs have been introduced into clinical practice. Special formulae and
      methods are suggested to aid the clinician to find the optimal EAD size,
      especially for children. CONCLUSION: Selecting the appropriate size of an EAD is
      critical to optimal use, although applying the correct size of an EAD has been
      subject of controversy, as recommendations on sizing differ substantially and are
      far from a coherent and universal sizing system. Successful use of an EAD depends
      in part on appropriate size selection, in addition to clinical judgment, as well
      as patient anatomy and physiology. Standardization in the use of EAD sizes and a
      consensus about a consistent size systematic of EADs would benefit to promote a
      safer clinical practice in airway management.

PMID- 24299920
TI  - Mechanotransduction in the lungs.
AB  - Mechanical ventilation may induce or aggravate lung injury, a phenomenon known as
      ventilator induced lung injury (VILI). On a macroscopic level, the effects of
      mechanical stress and strain on lung tissue are well described. Increased tidal
      volumes may lead to volutrauma, raised airway pressures may cause barotrauma and
      cyclic collapse and reopening of alveolar units contributes to atelectrauma.
      These three harmful mechanisms may lead to local and systemic pulmonary
      inflammatory response known as biotrauma. The purpose of this review was to
      elucidate fundamental mechanisms involved in the mechanotransduction of
      mechanical stimuli on a cellular level. Bronchial epithelial cells in the distal
      airways as well as alveolar epithelial cells are exposed to a variety of
      mechanical forces. These cells are involved in sensing and translation of
      mechanical stimuli into an inflammatory response. This review provides insight
      into current knowledge of cellular and molecular pathways during the process of
      pulmonary epithelial mechanosensation and mechanotransduction under different
      mechanical conditions. Since evidence for specific pathways is generally lacking
      in some fields of alveolar epithelial mechanotransduction, this article aims at
      providing reasonable hypothesis for further investigation. 

PMID- 24299921
TI  - Thirteen years' experience of pharmacokinetic monitoring and dosing of busulfan:
      can the strategy be improved?
AB  - BACKGROUND: A busulfan concentration monitoring and dosing service has been
      provided by Christchurch Hospital since 1998. This study aimed to see (1) the
      percentage of patients with an area under the concentration time curve (AUC)
      outside the target range and had dose adjustment, (2) how busulfan clearance (CL)
      relates to body weight, and (3) if fewer samples could be used to predict doses.
      METHODS: Blood samples were taken from patients after oral administration,
      usually at 0.5, 1, 1.5, and 6 hours, and after the start of a 2-hour intravenous
      (IV) infusion of busulfan, at 1, 2, 2.5, 3, 6, and 8 hours. Dose adjustment was
      made based on the AUC compared with the target range. The relationship of CL and
      body weight for the IV group was used to develop a revised IV dosing schedule.
      The bias and imprecision of AUCs estimated using fewer sampling points were
      examined to see if sampling could be economized. RESULTS: Data were available for
      150 patients but for 6 patients, data were incomplete and excluded. Of the
      remaining 144 patients (256 sample sets, 209 oral, 47 IV, 62% with repeats), 38%
      (IV) and 35% (oral) of patients had AUCs within the target range after the first
      dose. Dose adjustment was made in 47% and 34% of patients dosed IV and orally,
      respectively, after which there was a trend to more patients achieving the target
      AUC. A nonlinear relationship was found between CL and body weight. The initial
      IV dosing schedule was revised to take this into account. Sampling for busulfan
      concentration measurement at 3 points (2.5, 4, 8 hours) or 2 points (2.5, 8
      hours) after the start of the infusion enabled accurate and precise estimates of
      AUC0-24. CONCLUSIONS: Around two thirds of patients treated with busulfan were
      outside the target AUC range after the first dose. Dose adjustment was made in
      37% of patients. The relationship between CL and body weight was used to revise
      the initial IV dosing schedule. Sampling for AUC estimation could be reduced to 2
      time points after IV dosing.

PMID- 24299923
TI  - Sugar administration to newly emerged Aedes albopictus males increases their
      survival probability and mating performance.
AB  - Aedes albopictus male survival in laboratory cages is no more than 4-5 days when
      kept without any access to sugar indicating their need to feed on a sugar source
      soon after emergence. We therefore developed a device to administer energetic
      substances to newly emerged males when released as pupae as part of a sterile
      insect technique (SIT) programme, made with a polyurethane sponge 4 cm thick and
      perforated with holes 2 cm in diameter. The sponge was imbibed with the required
      sugar solution and due to its high retention capacity the sugar solution was
      available for males to feed for at least 48 h. When evaluated in lab cages,
      comparing adults emerged from the device with sugar solution vs the device with
      water only (as negative control), about half of the males tested positive for
      fructose using the Van Handel anthrone test, compared to none of males in the
      control cage. We then tested the tool in semi-field and in field conditions with
      different sugar concentrations (10%, 15%, and 20%) and compared results to the
      controls fed with water only. Males were recaptured by a battery operated manual
      aspirator at 24 and 48 h after pupae release. Rather high share 10-25% of
      captured males tested positive for fructose in recollections in the vicinity of
      the control stations, while in the vicinity of the sugar stations around 40-55%
      of males were positive, though variability between replicates was large. The
      sugar positive males in the control test may have been released males that had
      access to natural sugar sources found close to the release station and/or wild
      males present in the environment. Only a slight increase in the proportion of
      positive males was obtained by increasing the sugar concentration in the feeding
      device from 10% to 20%. Surprisingly, modification of the device to add a black
      plastic inverted funnel above the container reduced rather than increased the
      proportion of fructose positive males collected around the station. No evidence
      of difference in the capacity of sterile (irradiated with 30 Gy) males to take a
      sugar meal relative to fertile males was observed in field comparison. A clear
      effect of temperature and relative humidity (RH) on the rate of sugar positive
      males was observed, with an increase of temperature and a decrease in RH strongly
      increasing the % of sugar positive males. In large enclosures we tested the
      effect of our sugar supplying tool on the mating competitiveness of sterile vs
      fertile males, which produced an evident favorable effect both on sterile and
      fertile males.

PMID- 24299922
TI  - New insights into TRP channels: Interaction with pattern recognition receptors.
AB  - An increasing number of studies have implicated that the activation of innate
      immune system and inflammatory mechanisms are of importance in the pathogenesis
      of numerous diseases. The innate immune system is present in almost all
      multicellular organisms in response to pathogens or tissue injury, which is
      performed via germ-line encoded pattern-recognition receptors (PRRs) to recognize
      pathogen-associated molecular patterns (PAMPs) or dangers-associated molecular
      patterns (DAMPs). Intracellular pathways linking immune and inflammatory response
      to ion channel expression and function have been recently identified. Among ion
      channels, transient receptor potential (TRP) channels are a major family of non
      selective cation-permeable channels that function as polymodal cellular sensors
      involved in many physiological and pathological processes. In this review, we
      summarize current knowledge about classifications, functions, and interactions of
      TRP channels and PRRs, which may provide new insights into their roles in the
      pathogenesis of inflammatory diseases.

PMID- 24299924
TI  - Aedes albopictus (Skuse) males in laboratory and semi-field cages: release ratios
      and mating competitiveness.
AB  - To control the container-breeding mosquito and major vector of dengue and
      chikungunya Aedes albopictus, the sterile insect technique (SIT) is proposed as a
      component of integrated vector management programs in endemic areas. For the
      technique to be successful, released males, sterilized with 35 Gy of ionizing
      radiation during the pupal stage, must be able to compete for mating
      opportunities with wild counterparts and successfully copulate with wild females
      to induce sterility in the population. Any reduction in competitiveness can be
      compensated for by increasing the ratio of released sterile to wild males, a
      ratio which must be optimized for effectiveness and efficiency. Fruit fly SIT
      programs use field enclosures to test the competitiveness of sterile males to
      monitor the quality of the colony and adjust release ratios. This is laborious
      and time consuming, and for mosquito programs it would be advantageous if
      similarly useful results could be obtained by smaller scale laboratory tests,
      conducted on a more regular basis. In the present study we compared the
      competitiveness, as measured by hatching rate of resulting egg batches, of
      irradiated males measured in small and large laboratory cages and semi-field
      enclosures in a greenhouse setting, when competing in a 1:1, 3:1, and 5:1 ratio
      with fertile males. The sterile males were found to be equally competitive when
      compared to unirradiated counterparts, and a 5:1 ratio was sufficient to reduce,
      but not eliminate, the fertility of the female populations, irrespective of cage
      size. Variability in hatch rate in eggs laid by individual females and so-called
      indeterminate matings, when we could not be certain whether a female had mated a
      fertile or a sterile male, could be investigated by closer investigation of
      mating status and the frequency of multiple matings in Ae. albopictus. The
      laboratory results are encouraging for the effectiveness of the SIT using
      irradiated males of this species, and we support further assessment in the field.

PMID- 24299925
TI  - The HSP90 inhibitor 17-AAG potentiates the antileishmanial activity of the ether
      lipid edelfosine.
AB  - HSP90 is an abundant protein in Leishmania parasites that plays a major role in
      the parasite survival under stress conditions. Here we found that the HSP90
      inhibitor 17-AAG (>=100nM 17-AAG) induced cell cycle arrest at G0/G1 in
      Leishmania infantum and Leishmania panamensis promastigotes, and highly
      potentiated the induction of cell death by an apoptotic-like process mediated by
      the ether phospholipid edelfosine (5-20MUM). These data suggest that the combined
      treatment of 17-AAG and edelfosine might be a novel and effective approach of
      combination therapy in the treatment of leishmaniasis. 

PMID- 24299926
TI  - The bacterial-like HslVU protease complex subunits are involved in the control of
      different cell cycle events in trypanosomatids.
AB  - The trypanosomatid parasites Leishmania and Trypanosoma are responsible for the
      most important WHO-designated neglected tropical diseases, for which the need for
      cost-effective new drugs is urgent. In addition to the classical eukaryotic 20S
      and 26S proteasomes, these unconventional eukaryotes possess a bacterial-like
      protease complex, HslVU, made of proteolytic (HslV) and regulatory (HslU)
      subunits. In trypanosomatids, two paralogous genes are co-expressed: HslU1 and
      HslU2. Conflicting reports have been published with respect to subcellular
      localization, functional redundancy and putative roles of the different subunits
      of this complex in trypanosomatids. Here, we definitively established the
      mitochondrial localization of HslVU in L. major procyclic promastigotes and of
      HslV in T. brucei bloodstream trypomastigotes, the latter being the form
      responsible for the disease in the mammalian host. Moreover, our data demonstrate
      for the first time the essential nature of HslVU in the bloodstream
      trypomastigotes of T. brucei, in spite of mitochondrial repression at this stage.
      Interestingly, our work also allows distinguishing a specific role for the
      different members of the complex, as HslV and HslU1 appear to be involved in the
      control of different cell cycle events. Finally, these data validate HslVU as a
      promising drug target against these parasitic diseases of wide medical and
      economical importance. 

PMID- 24299927
TI  - An E3 ubiquitin ligase, ERECT LEAF1, functions in brassinosteroid signaling of
      rice.
AB  - A spontaneous rice mutant, erect leaf1 (elf1-1), produced a dwarf phenotype with
      erect leaves and short grains. Physiological analyses suggested that elf1-1 is
      brassinosteroid-insensitive, so we hypothesized that ELF1 encodes a positive
      regulator of brassinosteroid signaling. ELF1, identified by means of positional
      cloning, encodes a protein with both a U-box domain and ARMADILLO (ARM) repeats.
      U-box proteins have been shown to function as E3 ubiquitin ligases; in fact, ELF1
      possessed E3 ubiquitin ligase activity in vitro. However, ELF1 itself does not
      appear to be polyubiquitinated. Mutant phenotypes of 2 more elf1 alleles indicate
      that the entire ARM repeats is indispensable for ELF1 activity. These results
      suggest that ELF1 ubiquitinates target proteins through an interaction mediated
      by ARM repeats. Similarities in the phenotypes of elf1 and d61 mutants (mutants
      of brassinosteroid receptor gene OsBRI1), and in the regulation of ELF1 and
      OsBRI1 expression, imply that ELF1 functions as a positive regulator of
      brassinosteroid signaling in rice. 

PMID- 24299928
TI  - The effect of single low-dose dexamethasone on blood glucose concentrations in
      the perioperative period: a randomized, placebo-controlled investigation in
      gynecologic surgical patients.
AB  - BACKGROUND: The effect of single low-dose dexamethasone therapy on perioperative
      blood glucose concentrations has not been well characterized. In this
      investigation, we examined the effect of 2 commonly used doses of dexamethasone
      (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during
      the first 24 hours after administration. METHODS: Two hundred women patients were
      randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg
      dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg
      (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose
      concentrations were measured at baseline and 1, 2, 3, and 4 hours after
      administration in the early groups and at baseline and 8 and 24 hours after
      administration in the late groups. The incidence of hyperglycemic events (the
      number of patients with at least 1 blood glucose concentration >180 mg/dL) was
      determined. RESULTS: Blood glucose concentrations increased significantly over
      time in all control and dexamethasone groups (from median baselines of 94 to 102
      mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood
      glucose concentrations did not differ significantly between the groups receiving
      dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement
      time. The incidence of hyperglycemic events did not differ in any of the early
      (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. CONCLUSIONS: Because
      blood glucose concentrations during the first 24 hours after administration of
      single low-dose dexamethasone did not differ from those observed after saline
      administrations, these results suggest clinicians need not avoid using
      dexamethasone for nausea and vomiting prophylaxis out of concerns related to
      hyperglycemia.

PMID- 24299929
TI  - A randomized trial of the effects of antibiotic prophylaxis on epidural-related
      fever in labor.
AB  - BACKGROUND: It has been suggested that the development of maternal fever during
      epidural analgesia could be due to intrapartum infection. We investigated whether
      antibiotic prophylaxis before epidural placement decreases the rate of epidural
      related fever. METHODS: In this double-blind, placebo-controlled trial, 400
      healthy nulliparous women requesting epidural analgesia were randomly assigned to
      receive either cefoxitin 2 g or placebo immediately preceding initiation of
      epidural labor analgesia. Maternal tympanic temperature was measured hourly, and
      intrapartum fever was defined as a maternal temperature of >=38 degrees C.
      Neonates born to women with fever were evaluated for possible sepsis, and
      available placentas were evaluated for the presence of neutrophilic inflammation.
      The primary outcome was maternal fever during epidural analgesia. RESULTS: Thirty
      eight percent of women in the cefoxitin group and 40% of women in the placebo
      group developed fever (P = 0.68). The risk difference (95% confidence interval)
      for fever >=38 degrees C during labor (antibiotic versus placebo) was -2.0% (
      11.5 to 7.5), and for fever >39 degrees C during labor was -1.5% (-4.7 to 1.7).
      Approximately half of each study group had placental neutrophilic inflammation,
      but administration of cefoxitin had no significant effect on any grade of
      neutrophilic inflammation. Fever developed significantly more often in the women
      with placental neutrophilic inflammation compared with those without such
      inflammation (73/158 vs 33/144, P < 0.001; risk difference 23% [95% confidence
      interval, 13.0-34.0]). There were no significant differences in any neonatal
      outcomes between the antibiotic and placebo study groups. Sepsis was not
      diagnosed in any of the infants. There were no neonatal deaths. CONCLUSION: Fever
      during labor epidural analgesia is associated with placental inflammation, but
      fever and placental inflammation were not reduced with antibiotic prophylaxis.
      This finding suggests that infection is unlikely to be the cause in its
      development.

PMID- 24299930
TI  - Is dexamethasone associated with recurrence of ovarian cancer?
AB  - BACKGROUND: Basic science studies suggest that perioperative immune impairment
      may augment the risk of cancer recurrence after otherwise potentially curative
      surgery. Despite its immunosuppressant properties, dexamethasone is commonly
      given to oncologic patients in an effort to reduce postoperative nausea and
      vomiting. We therefore tested the hypothesis that perioperative dexamethasone
      administration increases the risk of ovarian cancer recurrence. METHODS: Women
      who had primary ovarian cytoreductive surgery between January 1997 and October
      2007 were identified using a database maintained by the division of Gynecologic
      Oncology at Northwestern University. Tumor recurrence in women given
      perioperative systemic dexamethasone (4-10 mg) was compared with those who did
      not receive dexamethasone. The primary outcome was the propensity-matched time to
      cancer recurrence. Recurrence was defined by a carcinoantigen 125 >21 U/mL or
      computerized tomography evidence of the disease followed by tissue confirmation.
      Median difference and 95% confidence interval between the propensity-matched
      groups were calculated using a 10,000 sample bootstrap. RESULTS: Among 260 women
      having primary cytoreductive surgery for ovarian cancer that met our inclusion
      criteria, 102 subjects were given perioperative systemic dexamethasone. Cancer
      recurrence was observed in 178 subjects, and the overall unadjusted median (IQR)
      time to recurrence was 18 (7-50) months. Eighty-seven cases and 87 controls were
      propensity matched to adjust for confounding covariates. After propensity
      matching the groups for confounding covariates, the median (IQR) time to
      recurrence in the dexamethasone group was 23 (6-46) compared with 18 (8-53)
      months in the control group (P = 0.63) with a median (95% confidence interval)
      difference of time to recurrence between the dexamethasone and the control group
      of 5 (-8 to 17) months. CONCLUSION: We could not find evidence for an association
      between perioperative systemic dexamethasone administration and ovarian cancer
      recurrence after primary cytoreductive surgery. Our results do not support
      avoiding low-dose perioperative dexamethasone for prevention of postoperative
      nausea, vomiting, and pain in ovarian cancer patients.

PMID- 24299931
TI  - Malignant hyperthermia in children: an analysis of the North American malignant
      hyperthermia registry.
AB  - BACKGROUND: Clinical characteristics of malignant hyperthermia (MH) in pediatric
      patients have not been elucidated. In this study, we used the North American
      Malignant Hyperthermia Registry to determine differences in clinical
      characteristics of acute MH across pediatric age groups. We hypothesized that
      there are differences in clinical presentation, clinical course, and outcomes,
      which correlate with age. A secondary aim was to determine the types of
      preexisting medical conditions associated with pediatric MH. METHODS: We
      performed a retrospective review of the North American Malignant Hyperthermia
      Registry to identify pediatric subjects (up to and including 18 years) with an MH
      clinical grading score at or above 35 indicating "very likely" or "almost
      certain" MH. Preoperative patient characteristics, perianesthetic factors, and
      outcome data were compared for 3 cohorts based on age: 0 to 24 months, 25 months
      to 12 years, and 13 to 18 years. We used statistical analysis to determine
      differences among the groups. RESULTS: We analyzed 264 records: 35 in the
      youngest age group, 163 in the middle age group, and 66 in the oldest group.
      There was no indication of any predisposing risk factors for MH based on family
      history or physical examination. Sinus tachycardia, hypercarbia, and rapid
      temperature increase were the most common signs of acute MH (observed in 73.1%,
      68.6%, and 48.5%, respectively) and were more common in the oldest age cohort.
      Higher maximum temperatures and higher peak potassium values were seen in the
      oldest age cohort. Masseter spasm was more common in the middle age cohort. The
      youngest age cohort was more likely to develop skin mottling and was
      approximately half as likely to develop muscle rigidity. The youngest age group
      also demonstrated significantly higher peak lactic acid levels and lower peak
      creatine kinase values. Treatments were similar across age cohorts. There were 10
      MH-associated deaths, 6 in the middle age group and 4 in the oldest age group.
      Recrudescence of symptoms after initial treatment occurred in 14.4% of subjects,
      with no difference across age cohorts. Two of these subjects, 1 in the middle age
      group and 1 in the oldest age group, died after the recrudescence event.
      CONCLUSIONS: There are differences in clinical characteristics of acute MH among
      different age cohorts in childhood. Older subjects demonstrated higher body
      temperatures and higher potassium levels, and the youngest subjects had greater
      levels of metabolic acidosis. Most children in each age group were phenotypically
      normal before developing MH.

PMID- 24299932
TI  - A randomized controlled trial of variable rate phenylephrine infusion with rescue
      phenylephrine boluses versus rescue boluses alone on physician interventions
      during spinal anesthesia for elective cesarean delivery.
AB  - BACKGROUND: Phenylephrine infusion is used to reduce hypotension during spinal
      anesthesia for cesarean delivery. A prophylactic fixed rate infusion regimen may
      not improve hemodynamic control; a variable rate regimen adjusted in response to
      changes in arterial blood pressure and heart rate may allow more accurate
      maintenance of baseline blood pressure. We hypothesized that a combination of
      crystalloid solution coload with a variable rate phenylephrine infusion and
      phenylephrine rescue boluses may be associated with fewer physician interventions
      needed to maintain maternal systolic blood pressure within 20% of baseline and
      greater hemodynamic stability than crystalloid solution coload with phenylephrine
      rescue boluses alone. METHODS: In this prospective, double-blind study, 80
      patients received a coload with 15 mL/kg lactated Ringer's solution immediately
      after the initiation of spinal anesthesia. Patients were randomized to receive a
      prophylactic variable rate phenylephrine infusion starting at 0.75 MUg/kg/min
      (group P) or infusion of normal saline (group S). Maternal systolic blood
      pressure was maintained within 20% of baseline with rescue phenylephrine boluses
      using a preset algorithm. During the predelivery period, the number of physician
      interventions (primary outcome), hemodynamic performance, nausea/vomiting, and
      umbilical cord blood gas values were compared between the groups. RESULTS: One
      patient from group S was excluded due to protocol violation. Therefore, group P
      included 40 patients and group S 39 patients. The median (range) number of
      physician interventions needed to maintain maternal hemodynamics within the
      target range (0 [0-6] vs 3 [0-9], difference in median: 3, 95% confidence
      interval of difference: 2-4) and incidence of hypotension (8/40 [20%] vs 35/39
      [90%]) were lower in group P compared with group S (P < 0.001). Group P had a
      higher incidence of hypertension compared with group S (6/40 [15%] vs 0/39 [0%],
      P = 0.026). The median performance error was closer to baseline (P < 0.001) with
      a smaller median absolute performance error (P = 0.001) in group P versus group
      S. In group P, 4/40 (10%) patients had nausea/vomiting compared with 17/39 (44%)
      in group S (P = 0.001). The number needed to treat was 1.4 women to prevent 1
      case of hypotension, and 3 women to prevent 1 case of nausea/vomiting; the rate
      of hypertension was 1 case per 6.7 women treated. Neonatal outcomes were not
      different between the 2 groups. CONCLUSION: Prophylactic variable rate
      phenylephrine infusion and rescue phenylephrine bolus dosing is more effective
      than relying on rescue phenylephrine bolus dosing with respect to limiting
      clinician workload and maternal symptoms during spinal anesthesia for cesarean
      delivery.

PMID- 24299933
TI  - Do Recent Advances in MR Technologies Contribute to Better Gamma Knife
      Radiosurgery Treatment Results for Brain Metastases?
AB  - The detection of intracerebral lesions has improved greatly with advancements in
      MR imaging, especially the greater sensitivity of the 1.5 Tesla unit versus the
      older 1.0 Tesla unit. We aimed to determine whether improvements in MR imaging
      have actually improved diagnostic capabilities and treatment outcomes in gamma
      knife radiosurgery (GKRS) for brain metastases (METs). Ours was a retrospective
      study of a consecutive series of 1179 patients (441 females, 738 males, mean age:
      63 years, range: 19-92 years) with brain METs who underwent GKRS from 1998 to
      2004. Our treatment policy was to irradiate all lesions visible on MR images
      during a single GKRS session. Mean and median tumor numbers were seven and three
      (range; 1-74). The 1179 patients were divided into two groups: a 1.0 T-group of
      660 patients examined using a 1.0 Tesla MR unit before August,2002, and a 1.5 T
      group of 519 examined using a 1.5 Tesla MR unit after September 2002. In the 1.5
      T-group, lesion volumes as small as 0.004 cc were detected with a 5 mm slice
      thickness. The corresponding lesion size was 0.013 cc in the 1.0 T-group. One or
      more lesions invisible on a 5 mm slice study were additionally detected on a 2 mm
      slice study in 47.8% of patients in the 1.0 T-group and 25.2% in the 1.5 T-group
      (p<.0001). The median survival time (MST) in the 1.5 T-group was significantly
      longer than that in the 1.0 T-group (8.4 vs. 6.3 months, p=.0004). Due to biases
      in patient numbers between the two groups, we analyzed subgroups with KPS of 80%
      or better, no neurological deficits, stable primary tumors, lung cancer, tumor
      numbers of four or less and tumor volumes of 10.0 cc or smaller. In every
      subgroup analysis, the MSTs of the 1.5-Tesla group were significantly longer than
      those of the 1.0-Tesla group. The prognosis of a cancer patient is undoubtedly
      influenced by multiple factors. Nevertheless, we conclude that application of the
      1.5 Tesla MR unit has had a favorable impact on diagnosis and GKRS treatment
      results in patients with brain METs. 

PMID- 24299934
TI  - On identifying micro level error in realignment phase of statistical parametric
      mapping.
AB  - Statistical parametric map of an fMRI time series is used to identify the sensor,
      motor and cognitive tasks in the specific regions of the brain. This process of
      obtaining statistical parametric map includes realignment of the slices in
      various volume acquired during the scanning. This article presents the
      identification of micro level (10(-6)) error in the realignment phase. 

PMID- 24299935
TI  - Brain MRI in fetuses with cardiac tumours.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder
      which affects the skin, brain, heart and other organs. It is caused by mutations
      of two genes: TSC1 (on chromosome 9q34) or TSC2 (on 16p13.3). 70% of cases are
      sporadic with new mutations. This study aimed to highlight the utility of
      prenatal MRI as an adjunct imaging modality in the diagnosis and prognosis of
      tuberous sclerosis complex. Prenatal ultrasound and magnetic resonance imaging
      were performed in seven fetuses at a gestational age of 30, 32, 34 and 35 weeks
      using a 1.5 T MRI scanner. SSFSE,T2- and FGRE/T1-weighted images were obtained in
      axial, coronal and sagittal planes. Postnatal MRI was performed in two cases.
      Intracardiac tumors (rhabdomyomas) were revealed on ultrasound in all fetuses. On
      sonographic examination the brain tissue appeared normal in all cases. Brain MRI
      revealed focal low-signal-intensity lesions, localized along the walls of the
      lateral ventricles of five fetuses. Another hypointense lesion was seen at the
      grey/white matter junction in one case. Brain MRI of two fetuses was normal. The
      diagnosis of TSC was established in five cases. Postnatal MRI in two cases
      confirmed prenatal findings. MRI allows more complete evaluation of the fetus and
      helps to determine the diagnosis and prognosis in cases of TSC. The use of
      prenatal MR imaging in addition to prenatal sonography has the potential to
      improve genetic counseling and prenatal diagnosis of patients with tuberous
      sclerosis. 

PMID- 24299936
TI  - Childhood spinal glioblastoma multiforme with intracranial dissemination. A case
      report.
AB  - Primary spinal cord tumors in children are uncommon and account for approximately
      5% of all pediatric central nervous system tumors. Intracranial metastases from
      primary spinal cord tumors have rarely been reported. Spinal cord glioblastoma in
      children mainly involves the thoracic region, whereas involvement of the
      medullaris conus with intracranial dissemination has been described in six cases.
      This paper describes a pediatric case of thoracic glioblastoma multiforme with
      intracranial dissemination in the early stage of the clinical course and discuss
      the clinical and neuroradiological manifestations, the possible patterns of
      dissemination and finally to consider the therapeutic implications. 

PMID- 24299937
TI  - Perirolandic sparing and pituitary apoplexy in adult brain with global hypoxia. A
      case report.
AB  - Global hypoxia in adult brain usually manifests as ischemic lesions in watershed
      territories. Acute profound hypoxia involves the cortex especially the
      perirolandic area, white matter and deep grey matter. Perirolandic sparing in
      adult global hypoxia is not described in literature. Few cases of perirolandic
      sparing are described in conditions like anoxia in term infants in the post
      neonatal period and hepatic encephalopathy. We report a case of global hypoxia in
      adult brain with perirolandic sparing and unique association with pituitary
      apoplexy. It is well known that the "diving reflex" redistribution of cerebral
      blood flow to the high metabolically active regions occurs when the hypoxic
      insult is prolonged and partial. The perirolandic sparing in our case could be
      explained by this phenomenon, wherein the patient acutely developed hypoxia,
      which was profound and prolonged but not prolonged enough for deep grey matter
      sparing. 

PMID- 24299938
TI  - Neuritis of the sixth cranial nerve. A case report.
AB  - Neuritis is an uncommon cause of sixth cranial nerve palsy. We describe the case
      of a young man with sixth cranial nerve palsy. Magnetic resonance examination
      revealed thickening and post contrast enhancement of the sixth cranial nerve
      interpreted as a sixth cranial neuritis. 

PMID- 24299939
TI  - Glossopharyngeal neuralgia due to vascular compression by tortuous left posterior
      inferior cerebellar artery: a high strength (1.5 T) MRI study.
AB  - Glossopharyngeal neuralgia is a rare condition with a frequency about 1% of that
      of trigeminal neuralgia. Vascular compression is a common and treatable cause of
      glossopharyngeal neuralgia. Microvascular decompression of the glossopharyngeal
      nerve is an effective treatment option for patients in whom the disease is caused
      by compression of the nerve by a blood vessel. Pre-operative detection of the
      pathology on imaging has become possible with high strength MRI imaging. We
      describe the case of a 54-year-old man with left glossopharyngeal neuralgia.
      Constructive interference in steady-state (CISS) and flow sensitive Gradient Echo
      MRI sequences clearly demonstrated the compression of the IX nerve by the left
      posterior inferior cerebellar artery (PICA). The patient was operated upon and a
      Teflon graft was put in between the nerve and the vessel. The intra-operative
      photographs and post-operative images are also presented here. After surgery, the
      patient improved symptomatically with no recurrence of the symptoms in the follow
      up period of about eight months. 

PMID- 24299940
TI  - Tuberculous meningitis: neuroimaging features, clinical staging and outcome.
AB  - Forty-two patients diagnosed with tuberculous meningitis in Kuala Lumpur Hospital
      based on clinical criteria, cerebrospinal fluid analysis and response to
      antituberculous treatment over a seven year period were included in this study.
      Relevant information was obtained from patients' medical case notes and
      neuroimaging findings were evaluated. The clinical presentation of patients was
      staged according to Medical Research Council for tuberculous meningitis. Fisher's
      Exact Test was used to determine the correlation between the neuroimaging
      features, clinical staging and outcome of patients. 52.4% of patients had stage 2
      disease, 28.6% stage 3 and the remainder stage 1 disease. 95.2% of patients had
      various neuroimaging abnormalities and only 4.8% had normal neuroimaging
      findings. The commonest neuroimaging findings were hydrocephalus and meningeal
      enhancement. 47.6% of patients survived without any complication. 23.8% developed
      morbidity either with minor or major neurological deficit and 28.6% had died at
      the end of the study period. Among patients with negative neuroimaging findings,
      one died and another one survived without any complication. Among patients with
      abnormal neuroimaging findings, 25% developed morbidity, 27.5% died and 47.5%
      survived without complication. The only neuroimaging feature significantly
      correlated with clinical outcome was the presence of hydrocephalus. Therefore,
      hydrocephalus is important in the prognosis of the disease and should be
      considered an indicator of poor clinical outcome. There was no significant
      correlation between clinical staging and clinical outcome, nor was there a
      significant correlation between clinical staging and individual neuroimaging
      features. 

PMID- 24299941
TI  - Imaging of isolated cerebral mucormycosis. A report of three cases.
AB  - Mucormycosis is a rare infection in immunosupressed patients caused by fungi from
      the family Mucoraceae. Three types of disease spread have been described:
      rhinocerebral, systemic and isolated. Isolated spread is the most uncommon form,
      usually resulting in death. It has been described in diabetics, immunosupressed
      patients and intravenous drug abusers. Neuroimaging can aid the diagnosis of this
      entity, but biopsy remains the only reliable method. Imaging findings of
      Mucormycosis include abscesses and hemorrhagic or ischemic infarcts, usually in
      the basal ganglia and frontal lobes. Single or multiple lesions have been
      described as well as meningoencephalitis. Understanding these findings can help
      to detect the infection in an early stage. We describe three cases of isolated
      cerebral mucormycosis; all of them were intravenous drug abusers with one patient
      also being HIV positive. 

PMID- 24299942
TI  - Interferon Beta-1b may reverse axonal dysfunction in multiple sclerosis.
AB  - Progression of the disability of multiple sclerosis (MS) is thought to be related
      to axonal damage that is seen even in normal appearing white matter (NAWM) of
      patients' brains. Interferon beta (IFNbeta) treatment for MS reduces the
      frequency of clinical exacerbations and the appearance of new inflammatory
      demyelinating lesions on magnetic resonance imaging (MRI). However, the effect of
      IFNbeta treatment on axonal damage in MS is not known. The present study aimed to
      assess the effect of IFNbeta on axonal function by comparing the data from
      localised single voxel proton MR spectroscopy (MRS) performed on eight MS
      patients given IFNbeta-1b treatment and 11 untreated patients. Brain MRI and MRS
      were performed before the initiation of IFNbeta-1b treatment and 24 months after
      treatment initiation. Levels of N-acetylaspartate (NAA), choline-containing
      compounds (Cho) and creatine (Cr) were calculated as the areas under their peaks
      shown on MRS and the ratios of NAA/Cr and Cho/Cr were calculated. In the patients
      treated with IFNbeta-1b there was a significant increase in the ratio of NAA/Cr
      in NAWM (p=0.028) at 24 months after the initiation of treatment. In contrast,
      there was no significant change in the NAA/Cr ratio in the untreated patients.
      These results suggest that IFNbeta-1b treatment might recover axonal function in
      NAWM of MS patients. 

PMID- 24299943
TI  - Typical Meningioma with Atypical MR Imaging Features Masquerading Malignancy. A
      Case Report.
AB  - Meningiomas are the most common extraaxial tumors of intracranial neoplasms. They
      are usually benign with characteristic pathologic and imaging features. However,
      a histologically typical meningioma can have unusual or misleading imaging
      features that may not be suggestive of meningioma. Unusual imaging features such
      as large meningeal cysts, ring enhancement, and various metaplastic changes can
      be particularly misleading. Here we present a fibrous meningioma with atypical
      magnetic resonance (MR) imaging features in a 76-year-old woman. 

PMID- 24299944
TI  - Increased oxidative stress and xanthine oxidase activity in human ruptured
      cerebral aneurysms.
AB  - Recent studies have suggested that oxidative stress may be involved in the
      development of arterial aneurysms. Xanthine oxidase is implicated in the
      generation of reactive oxygen species under pathological conditions in the
      cardiovascular system, and increased xanthine oxidase activity has been reported
      in human aortic aneurysms. We, therefore, studied the changes of xanthine oxidase
      activity and oxidative stress in human ruptured cerebral aneurysms. Six cerebral
      aneurysmal samples were obtained during surgery. Normal arteries of the similar
      size (one superficial temporal artery, four uterine arteries and three right
      gastroepiploic arteries) were used as controls. The xanthine oxidase activity was
      measured with a commercial assay kit, and its expression was localized by
      immunohistochemistry. The xanthine oxidase activity was significantly increased
      in aneurysms by 4.1 fold (P<0.05) compared to control arteries. This was
      accompanied by an elevated malondialdehyde (MDA) level (8.3+/-5.1 versus 2.9+/
      0.7 nmol/g protein, mean +/-SD, P<0.05), a marker of oxidative stress.
      Immunohistochemistry established that xanthine oxidase was mainly expressed in
      infiltrating inflammatory cells. Our study indicates that xanthine oxidase may
      have an important role in the increased oxidative stress in ruptured cerebral
      aneurysms. Further studies are needed to clarify the role of XO-derived reactive
      oxygen species in the development and rupture of cerebral aneurysms. 

PMID- 24299945
TI  - Anatomical subcategorization for pediatric vein of galen aneurysmal dilatation. A
      report of three cases.
AB  - Vein of Galen aneurysmal dilatation is generally considered an abnormal deep
      seated arteriovenous shunt that drains into the Vein of Galen. We herein present
      three pediatric cases of vein of Galen aneurysmal dilatation (VGAD). The
      locations of these shunts are anatomically different from just parenchymal as
      previously reported, but are also cisternal and intraventricular. Clinical
      symptoms, neuroradiological diagnostic points and therapeutic endovascular
      management are reported. Three boys had abnormal findings on brain computed
      tomography. Using magnetic resonance images, magnetic resonance angiography,
      three dimensional computed tomographical angiography and digital subtraction
      angiography, these patients were diagnosed with VGAD. The different locations of
      their shunts were the intraventricular choroidal plexus, cistern verum
      interpositive, and thalamus pulvinar nucleus. The boy presenting a single hole
      arteriovenous shunt at the cistern verum interpositive and an arteriovenous
      malformation at the choroidal plexus in the left lateral ventricle were treated
      by endovascular glue embolization. The patient with a single hole fistula in the
      left thalamus was followed only with observation. Treated patients had their
      abnormal shunts closed without any neurological complications. VGADs should be
      classified by shunt location according to whether they are ventricular,
      cisternal, or parenchymal. Although the therapeutic decision for pediatric VGAD
      should consider individual radiological, clinical and familial factors,
      endovascular intervention should be chosen as a first therapeutic option.
      Endovascular management of these lesions result in excellent angiographic and
      clinical outcome. 

PMID- 24299946
TI  - Transverse sinus thrombosis after posterior fossa surgery for cerebellar tumor
      treated by endovascular thrombectomy. A case report.
AB  - Dural sinus thrombosis is a rare complication after posterior fossa surgery,
      particularly in cerebellar tumour surgery. The authors describe the case of a
      young male patient who presented a postoperative neurological deterioration due
      to transverse sinus thrombosis after surgery for cerebellar medulloblastoma. He
      was treated by mechanical clot thrombectomy using an endovascular catch system
      technique without anticoagulation therapy. Final angiographic recanalization was
      obtained. This kind of endoluminal mechanical revascularization is an efficacious
      method to treat dural sinus thrombosis during perioperative time but speed in
      diagnosis is crucial for clinical outcome. 

PMID- 24299947
TI  - Surgical treatment of cervical arteriovenous fistula in a patient with
      neurofibromatosis type 1. A case report.
AB  - Vasculopathies are frequently associated with neurofibromatosis type-1, and they
      are generally occlusive or stenotic type lesions. Vertebral arteriovenous fistula
      (AVF) is quite rare in neurofibromatosis type 1 patients. They can be treated
      with surgical excision or endovascular occlusion. We describe a surgically
      treated cervical AVF in a neurofibromatosis type 1 (NF-1) patient and discuss the
      selection of the patient for the surgery. Although endovascular occlusion is the
      first line treatment option for cervical AVFs, some selected cases can be
      successfully treated by surgery. Surgery should be considered as a treatment
      option in spite of its risks, especially for cervical AVF which is associated
      with fibromuscular system diseases like NF-1. 

PMID- 24299948
TI  - Persistent hypoglossal artery associated with a ruptured ipsilateral posterior
      inferior cerebellar artery aneurysm. A case report.
AB  - A rare case of persistent hypoglossal artery in conjuction with a ruptured
      aneurysm at the left proximal posterior inferior cerebellar artery (PICA) is
      presented. A ruptured PICA aneurysm was successfully treated by endovascular
      occlusion of the aneurym with coiling. 

PMID- 24299949
TI  - Diffusion Tensor Imaging and 3D Tractography of the Cervical Spinal Cord Using
      the ECG-Gated Line-scan Technique. A Feasibility Study.
AB  - Diffusion tensor (DT) magnetic resonance (MR) imaging in addition to conventional
      MR images provide valuable information on the brain. This study compared line
      scan DT imaging with and without the ECG-gating technique to estimate clinical
      usefulness of the line scan diffusion tensor image (LSDTI) with ECG-gating in
      evaluating spinal cord diseases in vivo. First, five healthy volunteers
      participated in the comparison study. LSDWI was performed in three to five
      sagittal sections with a pulsed-field-gradient diffusion preparation pulse
      employing two different b-values (0 and 700 s/mm(2)) along six directions.
      Apparent diffusion coefficient (ADC) maps and fractional anisotropy (FA) were
      calculated and three-dimensional tract reconstruction and color schemes of the
      spinal cord were obtained. Image quality and the acquisition time of each LSDTI
      were compared. Second, LSDTI with ECG-gating was performed in eighteen patients
      with cervical spinal cord disorders and evaluated by two neuroradiologists.
      Images with the ECG-gated technique were all superior to those without ECG
      gating. Mean extended time for LSDTI with ECG-gating was approximately two
      minutes. In clinical use, the ADC and FA of spinal cord in patients with cervical
      spondylotic myelopathy statically changed. Moreover, demonstration of fibers was
      correlated with clinical symptoms. ECG-gating technique is preferable to LSDTI.
      The ADC and FA measurements and 3D fiber tracking of LSDTI with ECG-gating are
      promising methods to estimate cervical spinal cord pathology in clinical use. 

PMID- 24299950
TI  - Vertebral body signal changes in spinal cord infarction: histopathological
      confirmation.
AB  - Spinal cord infarctions are rare. They are difficult to diagnose clinically and
      remain undiagnosed even after extensive investigations. Magnetic Resonance (MR)
      features include hyperintensity of the cord on T2W images. Few cases of spinal
      cord infarction associated with vertebral body infarction are reported in the
      literature. We describe another five cases of spinal cord infarction with
      histopathological confirmation of the vertebral body signal changes. MR
      examinations of five patients who presented with acute spontaneous spinal cord
      syndrome were reviewed. Abnormal MR features of the spinal cord included signal
      changes within the parenchyma, best demonstrated on T2W images. These cord
      changes were associated with vertebral body T2 hyperintensity in all the patients
      and in one patient, the computed tomography guided biopsy of vertebral body
      lesion reported infarction. MR is sensitive to detect spinal cord infarctions and
      associated vascular and bony changes. The associated signal abnormalities in the
      bone marrow are a corroborative sign in the diagnosis of spinal cord infarction
      which was proved by histopathology. 

PMID- 24299951
TI  - Frontoethmoidal Mucoceles: CT and MRI Evaluation.
AB  - Paranasal sinus mucocele is an expanded, airless, mucus-filled sinus caused by
      obstruction of the sinus ostium. It is a benign slow growing epithelial lined
      lesion, bulging against adjacent anatomical structures, without infiltrating
      them. The purpose of our study is to describe the CT and MR findings in 19
      patients (ten women, nine men, 18-72 years, mean age: 48.1) with surgically
      confirmed frontoethmoidal mucoceles between 1999-2005. CT scans displayed
      mucoceles as non enhancing soft tissue density lesions, generally isodense to the
      brain parenchyma, expanding the sinuses in most cases, eroding adjacent bones and
      extending intraorbitally or intracranially. Signal intensity in T2WI and T1WI MR
      images varied, but generally lesions had high signal intensity in T2WI and low to
      intermediate signal intensity in T1WI. Some of the lesions demonstrated regular
      linear peripheral enhancement after administration of contrast medium. The causes
      of mucoceles included mucosal thickening from chronic sinusitis, adhesions from
      previous operation in the nasal cavity, previous trauma, small nasal polyps and a
      small osteoma, while in six patients (31.5%) the cause of the mucocele remained
      unrecognized even after surgery. No underlying malignant tumor was found in any
      of the cases as the cause of obstruction. CT and MRI established the correct
      diagnosis in all patients. CT was more sensitive in determining bone erosions,
      while MRI had the advantage of multiplanar imaging and was much more sensitive
      for differentiating mucocele from a tumor on the basis of MR signal intensity
      characteristics. In conclusion, CT and MRI are the methods of choice for
      diagnosing mucoceles of the paranasal sinuses and are of major importance for the
      treatment plan. Each method seems to have its own advantages and should be used
      as complementary investigations of sinonasal pathology. Enhanced CT scan should
      only be performed in the absence or contraindication for enhanced MR imaging. 

PMID- 24299952
TI  - TNFalpha induces the expression of genes associated with endothelial dysfunction
      through p38MAPK-mediated down-regulation of miR-149.
AB  - MicroRNAs have been proposed as novel regulators of vascular inflammation and
      dysfunction. This study aimed to evaluate the role of miR-149 in regulating the
      expression of key molecules associated with TNFalpha-induced endothelial
      activation. miR-149 was selected by in silico analysis and microRNA target
      prediction. Endothelial dysfunction was induced by TNFalpha treatment in Eahy926
      endothelial cells and HUVEC. miR-149 level was evaluated by quantitative real
      time-polymerase chain reaction (RT-qPCR). Metalloproteinase-9 (MMP-9) was
      measured by zymography, Inducible Nitric Oxide Synthase (iNOS) by immunoblotting,
      Interleukin-6 (IL-6) and Interleukin-8 (IL-8) by ELISA. miR-149 regulatory effect
      was evaluated by gain-of-function technique upon miR-149 mimics transfection.
      TNFalpha down-modulated miR-149 level in Eahy926 and HUVEC. This effect was
      significantly abolished in Eahy926 by treatment with p38MAPK inhibitor. miR-149
      mimic transfection counteracted the TNFalpha-induced expression of MMP-9, iNOS
      and IL-6. No effect was detected on IL-8 expression. Our results suggest that miR
      149 represents an important new regulator of endothelial function through
      negative regulation of molecules associated with TNFalpha-induced endothelial
      dysfunction. 

PMID- 24299953
TI  - Nuclear AXIN2 represses MYC gene expression.
AB  - The beta-catenin transcriptional coactivator is the key mediator of the canonical
      Wnt signaling pathway. In the absence of Wnt, beta-catenin associates with a
      cytosolic and multi-protein destruction complex where it is phosphorylated and
      targeted for proteasomal degradation. In the presence of Wnt, the destruction
      complex is inactivated and beta-catenin translocates into the nucleus. In the
      nucleus, beta-catenin binds T-cell factor (TCF) transcription factors to activate
      expression of c-MYC (MYC) and Axis inhibition protein 2 (AXIN2). AXIN2 is a
      member of the destruction complex and, thus, serves in a negative feedback loop
      to control Wnt/beta-catenin signaling. AXIN2 is also present in the nucleus, but
      its function within this compartment is unknown. Here, we demonstrate that AXIN2
      localizes to the nuclei of epithelial cells within normal and colonic tumor
      tissues as well as colorectal cancer cell lines. In the nucleus, AXIN2 represses
      expression of Wnt/beta-catenin-responsive luciferase reporters and forms a
      complex with beta-catenin and TCF. We demonstrate that AXIN2 co-occupies beta
      catenin/TCF complexes at the MYC promoter region. When constitutively localized
      to the nucleus, AXIN2 alters the chromatin structure at the MYC promoter and
      directly represses MYC gene expression. These findings suggest that nuclear AXIN2
      functions as a rheostat to control MYC expression in response to Wnt/beta-catenin
      signaling. 

PMID- 24299954
TI  - Active site proton delivery and the lyase activity of human CYP17A1.
AB  - Cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the
      intersection of corticoid and androgen biosynthesis and thus occupies an
      essential role in steroid hormone metabolism. This multifunctional enzyme
      catalyzes the 17alpha-hydroxylation of Delta4- and Delta5-steroids progesterone
      and pregnenolone to form the corresponding 17alpha-hydroxy products through its
      hydroxylase activity, and a subsequent 17,20-carbon-carbon scission of pregnene
      side chain produce the androgens androstenedione (AD) and dehydroepiandrosterone
      (DHEA). While the former hydroxylation reaction is believed to proceed through a
      conventional "Compound I" rebound mechanism, it has been suggested that the
      latter carbon cleavage is initiated by an iron-peroxy intermediate. We report on
      the role of Thr306 in CYP17 catalysis. Thr306 is a member of the conserved
      acid/alcohol pair thought to be essential for the efficient delivery of protons
      required for hydroperoxoanion heterolysis and formation of Compound I in the
      cytochromes P450. Wild type and T306A CYP17A1 self-assembled in Nanodiscs were
      used to quantitate turnover and coupling efficiencies of CYP17's physiological
      Delta4- and Delta5-substrates. We observed that T306A co-incorporated in
      Nanodiscs with its redox partner cytochrome P450 oxidoreductase, coupled NADPH
      only by 0.9% and 0.7% compared to the wild type (97% and 22%) during the
      conversion of pregnenolone and progesterone, respectively, to the corresponding
      17-OH products. Despite increased oxidation of pyridine nucleotide, hydroxylase
      activity was drastically diminished in the T306A mutant, suggesting a high degree
      of uncoupling in which reducing equivalents and protons are funneled into non
      productive pathways. This is similar to previous work with other P450 catalyzed
      hydroxylation. However, catalysis of carbon-carbon bond scission by the T306A
      mutant was largely unimpeded by disruption of the CYP17A1 acid-alcohol pair. The
      unique response of CYP17A1 lyase activity to mutation of Thr306 is consistent
      with a reactive intermediate formed independently of proton delivery in the
      active site, and supports involvement of a nucleophilic peroxo-anion rather than
      the traditional Compound I in catalysis. 

PMID- 24299955
TI  - Characterization of vegetative storage protein (VSP) and low molecular proteins
      induced by water deficit in stolon of white clover.
AB  - In stolon of white clover (Trifolium repens L.), the 17.3 kDa protein has been
      newly identified as a vegetative storage protein (VSP) which has preponderant
      roles in N accumulation and mobilization to sustain growth when capacity of N
      uptake is strongly reduced. To characterize the water deficit effect on this
      protein, the kinetic pattern of soluble protein, SDS-PAGE, Western blotting, and
      proteomic analysis was studied in the stolon of white clover during 28 days of
      water-deficit. Water deficit led to decrease protein concentration. SDS-PAGE
      revealed that two major proteins of 17.3 and 16 kDa were accumulated to high
      level in response to water stress. These proteins cross-reacted positively with
      antibodies raised against the 17.3 kDa VSP, a protein which shared biochemical
      features with stress proteins implied in dehydration tolerance. Using two
      dimensional electrophoresis (2-DE) gel and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometer (MALDI-TOF-MS) analysis,
      it was demonstrated that 19.5 and 17.3 kDa protein spots were up-regulated by
      water stress, and both spots were identical to nucleoside diphosphate kinase
      (NDPK) and lipid transfer proteins (LTPs), respectively. These results suggest
      that low molecular proteins induced by water-deficit in the stolon of white
      clover act as an alternative N reserves or play significant roles in plant
      protection against water-deficit stress.

PMID- 24299956
TI  - Induction of oxiapoptophagy, a mixed mode of cell death associated with oxidative
      stress, apoptosis and autophagy, on 7-ketocholesterol-treated 158N murine
      oligodendrocytes: impairment by alpha-tocopherol.
AB  - 7-Ketocholesterol (7KC) has been suggested to induce a complex mode of cell death
      on monocytic cells: oxiapoptophagy (OXIdation, APOPTOsis, and autoPHAGY) (Monier
      et al. (2003) [12]). The aim of the present study, realized on 158N murine
      oligodendrocytes, was to bring new evidence on this mixed form of cell death. On
      158N cells, 7KC induces an overproduction of reactive oxygen species (ROS)
      revealed by dihydroethidium staining, a loss of transmembrane mitochondrial
      potential measured with DiOC6(3), caspase-3 activation, and condensation and/or
      fragmentation of the nuclei which are typical criteria of oxidative stress and
      apoptosis. Moreover, 7KC enhances cytoplamic membrane permeability to propidium
      iodide, and induces acidic vesicular organelle formation evaluated with acridine
      orange. In addition, 7KC promotes conversion of microtubule-associated protein
      light chain 3 (LC3-I) to LC3-II which is characteristic of autophagy. These
      different side effects were impaired by alpha-tocopherol. Altogether, our data
      demonstrate that oxiapoptophagy including ROS overproduction, apoptosis and
      autophagy could be a particular type of cell death activated by 7KC which can be
      inhibited by alpha-tocopherol. 

PMID- 24299957
TI  - Hyperoxia inhibits glucose-induced insulin secretion and mitochondrial metabolism
      in rat pancreatic islets.
AB  - Isolated pancreatic islets containing the insulin-producing beta cells are devoid
      of circulation. They may therefore experience hypoxia with possible negative
      effects on beta cell function and survival. We investigated (1) whether hyperoxia
      in vitro would be beneficial by counteracting putative effects of lost
      circulation and, further, (2) whether previous hyperoxia would attenuate the
      impact of subsequently induced severe hypoxia. Islets from Sprague-Dawley rats
      were exposed to 95% O2 for 18 h. This hyperoxic exposure diminished glucose
      induced insulin secretion by 47% and inhibited oxygen consumption by 39-41%.
      Mitochondrial complexes I-III were decreased by 29-37%. Negative effects on
      insulin secretion and complexes III and IV waned after a 22 h period of normoxia
      following hyperoxia whereas complexes I and II were still diminished, ROS
      production was increased and rates of apoptosis tended to be increased (P=0.07).
      The effects of previous hyperoxia on susceptibility to damage by subsequent
      hypoxia were tested after 5.5h of 0.8% O2. Previous hyperoxia did not affect
      hypoxia-induced enhancement of HIF-1 alpha but modestly and significantly
      attenuated hypoxia-induced decreases in insulin contents. We conclude that
      hyperoxia exerts largely negative effects on beta cells, effects which are
      functional and possibly also toxic. A paradoxical positive finding (attenuation
      of hypoxia-induced effects) could be secondary to a protective effect of the
      hyperoxia-induced reduction of oxidative metabolism.

PMID- 24299958
TI  - Quantitative and temporal control of oxygen microenvironment at the single islet
      level.
AB  - Simultaneous oxygenation and monitoring of glucose stimulus-secretion coupling
      factors in a single technique is critical for modeling pathophysiological states
      of islet hypoxia, especially in transplant environments. Standard hypoxic chamber
      techniques cannot modulate both stimulations at the same time nor provide real
      time monitoring of glucose stimulus-secretion coupling factors. To address these
      difficulties, we applied a multilayered microfluidic technique to integrate both
      aqueous and gas phase modulations via a diffusion membrane. This creates a
      stimulation sandwich around the microscaled islets within the transparent
      polydimethylsiloxane (PDMS) device, enabling monitoring of the aforementioned
      coupling factors via fluorescence microscopy. Additionally, the gas input is
      controlled by a pair of microdispensers, providing quantitative, sub-minute
      modulations of oxygen between 0-21%. This intermittent hypoxia is applied to
      investigate a new phenomenon of islet preconditioning. Moreover, armed with
      multimodal microscopy, we were able to look at detailed calcium and KATP channel
      dynamics during these hypoxic events. We envision microfluidic hypoxia,
      especially this simultaneous dual phase technique, as a valuable tool in studying
      islets as well as many ex vivo tissues. 

PMID- 24299959
TI  - Gene expression profiles of inflammatory breast cancer: correlation with response
      to neoadjuvant chemotherapy and metastasis-free survival.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease. To date,
      no molecular feature reliably predicts either the response to chemotherapy (CT)
      or the survival. Using DNA microarrays, we searched for multigene predictors.
      PATIENTS AND METHODS: The World IBC Consortium generated whole-genome expression
      profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for
      transcriptional profiles associated with pathological complete response (pCR) to
      neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in
      respective subsets of 87 and 106 informative IBC samples. Correlations were
      investigated with predictive and prognostic gene expression signatures published
      in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of
      19 biological pathways and 234 transcription factors. RESULTS: Three of five
      tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated
      between IBC with and without pCR, as well as two interferon activation
      signatures. We identified a 107-gene signature enriched for immunity-related
      genes that distinguished between responders and nonresponders in IBC. Its
      robustness was demonstrated by external validation in three independent sets
      including two IBC sets and one nIBC set, with independent significant predictive
      value in IBC and nIBC validation sets in multivariate analysis. We found no
      robust signature associated with DMFS in patients with IBC, and neither of the
      tested prognostic GES, nor the molecular subtypes were informative, whereas they
      were in our nIBC series (220 stage I-III informative samples). CONCLUSION:
      Despite the relatively small sample size, we show that response to neoadjuvant CT
      in IBC is, as in nIBC, associated with immunity-related processes, suggesting
      that similar mechanisms responsible for pCR exist. Analysis of a larger IBC
      series is warranted regarding the correlation of gene expression profiles and
      DMFS.

PMID- 24299960
TI  - Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an
      audit of raltitrexed for patients with cardiac toxicity induced by
      fluoropyrimidines.
AB  - BACKGROUND: Cardiac toxicity an uncommon but serious side-effect of some
      fluoropyrimides. Cardiac toxicity from raltitrexed is rarely reported. With this
      background, we initiated this study to investigate the incidence of cardiac
      events in patients who had switched to raltitrexed following cardiac toxicity
      from fluoropyrimidines (5-fluorouracil or capecitabine). PATIENTS AND METHODS:
      Pharmacy records were used to identify patients receiving raltitrexed from
      January 2004 till March 2012. Medical records were then reviewed to confirm the
      use of raltitrexed after cardiac toxicity from 5-fluorouracil or capecitabine.
      The primary end point was the rate of further cardiac events after commencing
      raltitrexed. RESULTS: Forty-two patients were identified and the majority had
      colorectal cancer. Prior regimens included 5-fluorouracil +/- leucovorin,
      capecitabine alone, FOLFOX, FOLFIRI, epirubicin/cisplatin/5-fluorouracil, and
      capecitabine/oxaliplatin. Seven patients (17%) had bolus 5-fluorouracil regimens,
      26 patients (62%) had infusion 5-fluorouracil regimens, and 9 patients (21%) had
      capecitabine alone or in combination. Angina was the most common cardiac toxicity
      from 5-fluorouracil or capecitabine and usually occurred in the first or the
      second cycle. Four patients after their first cardiac event continued with the
      same 5-fluorouracil or capecitabine regimen with the addition of nitrates and
      calcium antagonists but still had further cardiac events. After changing to
      raltitrexed, either as a single agent or a continuing combination regimen, no
      patients experienced further cardiac toxicity. CONCLUSION: Raltitrexed is
      associated with no significant cardiac toxicity in patients who have experienced
      prior cardiac toxicity from 5-fluorouracil or capecitabine. Raltitrexed, alone or
      in combination with oxaliplatin or irinotecan, provides a safe option in terms of
      cardiac toxicity for such patients.

PMID- 24299961
TI  - Increased body mass index is associated with improved overall survival in diffuse
      large B-cell lymphoma.
AB  - BACKGROUND: Obesity is a well-known risk factor for the development of several
      types of cancer including lymphomas, but its influence on the course of disease
      is fairly unknown. Recently, a retrospective cancer registry analysis
      demonstrated significantly prolonged survival for overweight and obese patients
      with diffuse large B-cell lymphoma (DLBCL). The study population almost
      exclusively consisted of male US American patients of lower socioeconomic status
      and one-fifth of patients received cyclophosphamide, doxorubicin, vincristine,
      prednisone (CHOP) chemotherapy without rituximab. Therefore, it remains unclear
      if these results can be extrapolated to the general DLBCL population. PATIENTS
      AND METHODS: This retrospective single-center analysis included 183 unselected
      DLBCL patients who were treated with rituximab and standard-dosed anthracycline
      based chemoimmunotherapy as first-line therapy between January 2004 and December
      2012. Patients were stratified by body mass index (BMI) into 'low BMI' (<25.0
      kg/m(2)) and 'high BMI' (>=25.0 kg/m(2)). RESULTS: The two groups were well
      balanced regarding age, performance score, international prognostic index, B
      symptoms and extranodal involvement. However, there was a trend for male sex (P =
      0.053) and higher-stage disease (P = 0.066) in the high-BMI group. Patients with
      higher BMI had significantly longer overall survival (OS; hazard ratio [HR]
      0.546; P = 0.035) with 80.9% of patients alive at 3 years versus 64.2% in the low
      BMI group. BMI was also an independent prognostic factor for OS in multivariate
      analysis (HR 0.557; P = 0.043). CONCLUSION: We could show a significant
      association between overweight/obesity and improved OS in an unselected DLBCL
      cohort.

PMID- 24299962
TI  - Radiation therapy for extramammary Paget's disease: treatment outcomes and
      prognostic factors.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy,
      and there are few reports related to radiation therapy. In the present study, we
      investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS:
      Forty-one patients with EMPD in the genitalia underwent radiation therapy with
      curative intent. Fifteen patients had regional lymph node metastases before
      radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy
      (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33
      fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had
      developed recurrences, including 5 with local progression within the radiation
      field and 12 with lymph node or/and distant metastases outside the radiation
      field. The local progression-free and disease-free rates were 88% and 55% at 3
      years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73
      months after irradiation; the causes of death were tumor progression in five
      patients, infectious pneumonia in two, renal failure in one and old age in one.
      The overall and cause-specific survival rates were 93% and 96% at 3 years, and
      68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional
      lymph node metastasis were significant prognostic factors for both distant
      metastasis and survival. No therapy-related toxicities of grade >=3 were
      observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with
      EMPD. It appeared to contribute to prolonged survival owing to good tumor
      control, and to be a promising curative treatment option.

PMID- 24299963
TI  - Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7,
      12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats.
AB  - Globally, breast cancer is the second most prevalent cancer among women and its
      incidence is amplifying alarmingly. Since genetics is believed to account for
      only 10% of the reported cases, the environmental factors including diet are
      thought to play a significant role in predisposing breast cancer. Many bioactive
      compounds of plant origin have been reported for their anticancer potential.
      Tangeretin, a pentamethoxy flavone, is a naturally occurring phytoconstituent
      found to be present in significant amounts in the peel of citrus fruits.
      Tangeretin possess a wide array of pharmacological activities such as cytostatic,
      anti-proliferative and antioxidant properties. In the absence of systemic studies
      in the literature, the present study was aimed to evaluate the chemotherapeutic
      potential of tangeretin in 7, 12-dimethyl benz(a)anthracene (DMBA) induced
      mammary carcinoma in rats. Oral treatment of tangeretin (50 mg/kg BW) to breast
      tumor bearing rats daily for four weeks was found to be effective against DMBA
      induced mammary gland carcinogenesis in female Wistar rats. The increased
      activities of AST, ALT, ALP, ACP, 5'-ND, gamma-GT and LDH in serum of control and
      experimental breast cancer rats were significantly (p < 0.05) decreased to near
      normal levels. Further, the levels of lipid peroxide (TBARS), enzymatic
      antioxidants such as SOD, CAT, GPx and non-enzymatic antioxidants such as GSH,
      Vitamin C, Vitamin E and Phase I (cytochrome P450, cytochrome b5, EROD, MROD and
      PROD) and Phase II detoxification (glutathione S-transferase (GST), quinone
      reductase (QR)) were decreased significantly by administration of tangeretin.
      Immunohistochemical and western blotting studies for estrogen receptor,
      progesterone receptor and HER2/neu status exemplified the chemotherapeutic effect
      of tangeretin. Further, the histological and ultrastructural analysis of breast
      tissues evidenced the anti-tumorigenic nature of tangeretin. Thus, the results of
      the present study clearly indicate that tangeretin significantly suppresses DMBA
      induced breast cancer in rats. 

PMID- 24299964
TI  - In vivo 19F MRI for cell tracking.
AB  - In vivo (19)F MRI allows quantitative cell tracking without the use of ionizing
      radiation. It is a noninvasive technique that can be applied to humans. Here, we
      describe a general protocol for cell labeling, imaging, and image processing. The
      technique is applicable to various cell types and animal models, although here we
      focus on a typical mouse model for tracking murine immune cells. The most
      important issues for cell labeling are described, as these are relevant to all
      models. Similarly, key imaging parameters are listed, although the details will
      vary depending on the MRI system and the individual setup. Finally, we include an
      image processing protocol for quantification. Variations for this, and other
      parts of the protocol, are assessed in the Discussion section. Based on the
      detailed procedure described here, the user will need to adapt the protocol for
      each specific cell type, cell label, animal model, and imaging setup. Note that
      the protocol can also be adapted for human use, as long as clinical restrictions
      are met. 

PMID- 24299966
TI  - Primary endocrine therapy as an approach for patients with localized breast
      cancer deemed not to be surgical candidates.
AB  - PURPOSE OF REVIEW: For women diagnosed with localized hormone-receptor-positive
      breast cancer who have a poor performance status or who have medical conditions
      precluding aggressive treatment with chemotherapy or surgery, primary endocrine
      therapy has been proposed as a therapeutic alternative. Given that society is
      rapidly aging overall, this subset of patients will likely become a greater
      proportion of the patient population seen by breast cancer specialists. RECENT
      FINDINGS: On the basis of the results from randomized trials in patients whose
      health does not permit surgery, it appears that tamoxifen achieves a similar
      overall survival compared with surgery plus tamoxifen, supporting the use of
      primary endocrine therapy. In the neoadjuvant setting, aromatase inhibitors
      appear superior to tamoxifen, suggesting that these agents may be the best choice
      in the primary endocrine therapy setting. In addition, new breakthroughs for the
      management of hormone-receptor-positive disease in the metastatic setting have
      recently been reported. SUMMARY: This review will discuss the rationale and
      evidence for primary endocrine therapy; which agents could be selected for use;
      and how recent advances for the management of hormone-receptor-positive disease
      may potentially apply to this population.

PMID- 24299965
TI  - Use of Galleria mellonella as a model organism to study Legionella pneumophila
      infection.
AB  - Legionella pneumophila, the causative agent of a severe pneumonia named
      Legionnaires' disease, is an important human pathogen that infects and replicates
      within alveolar macrophages. Its virulence depends on the Dot/Icm type IV
      secretion system (T4SS), which is essential to establish a replication permissive
      vacuole known as the Legionella containing vacuole (LCV). L. pneumophila
      infection can be modeled in mice however most mouse strains are not permissive,
      leading to the search for novel infection models. We have recently shown that the
      larvae of the wax moth Galleria mellonella are suitable for investigation of L.
      pneumophila infection. G. mellonella is increasingly used as an infection model
      for human pathogens and a good correlation exists between virulence of several
      bacterial species in the insect and in mammalian models. A key component of the
      larvae's immune defenses are hemocytes, professional phagocytes, which take up
      and destroy invaders. L. pneumophila is able to infect, form a LCV and replicate
      within these cells. Here we demonstrate protocols for analyzing L. pneumophila
      virulence in the G. mellonella model, including how to grow infectious L.
      pneumophila, pretreat the larvae with inhibitors, infect the larvae and how to
      extract infected cells for quantification and immunofluorescence microscopy. We
      also describe how to quantify bacterial replication and fitness in competition
      assays. These approaches allow for the rapid screening of mutants to determine
      factors important in L. pneumophila virulence, describing a new tool to aid our
      understanding of this complex pathogen. 

PMID- 24299967
TI  - Morphometric, molecular and ecological analyses of the parasites of the
      sharpsnout seabream Diplodus puntazzo Cetti (Sparidae) from the Spanish
      Mediterranean: implications for aquaculture.
AB  - One of the fish species with the highest potential for aquaculture is the
      sharpsnout seabream, Diplodus puntazzo Cetti. Among other aspects, the
      development of new fish cultures requires studies of potential pathogens that may
      compromise survival of the fish in captivity. Moreover, both cultured and wild
      fish can act as sources or reservoirs of pathogens which may negatively affect
      other well-established cultures. We have studied the parasite fauna of the wild
      sharpsnout seabream, and monitored the survival of the parasites in culture
      conditions. The sharpsnout seabream was sampled from two different Spanish
      localities and examined for parasites. Additionally, 20 fish were maintained in
      captivity. Ten of them were examined for parasites after a period of 10 days and
      a further ten fish after another 10 days. All fish were parasitized with at least
      four species, with 19 parasite species being identified, seven of which were
      recorded for the first time in the sharpsnout seabream. These included
      Microcotyle sp., Magnibursatus bartolii, Steringotrema pagelli, Galactosomum sp.,
      Cardiocephaloides longicollis, Caligus ligusticus and Gnathia vorax. We also
      report the first records of two parasite species in the wild sharpsnout seabream,
      the polyopisthocotylean monogeneans Atrispinum seminalis and Sparicotyle
      chrysophrii. Previously, these parasites had only been recorded in farmed
      sharpsnout seabream. Most parasites in the skin, gills and alimentary tract
      disappeared under the conditions of captivity, with the exception of the
      monogeneans of the genus Lamellodiscus. The information provided about the
      sharpsnout seabream parasite fauna will be useful to prevent possible problems in
      fish farms due to some parasite species. Many parasites of the sharpsnout
      seabream recorded in the present study are shared by the main fish species in
      Mediterranean aquaculture, the gilthead seabream, thus suggesting the possibility
      of cross-infections. 

PMID- 24299969
TI  - Association of early PSA failure time with increased distant metastasis and
      decreased survival in prostate brachytherapy patients.
AB  - BACKGROUND AND PURPOSE: We investigated whether earlier PSA failure following
      prostate brachytherapy is associated with increased rates of distant metastases
      (DM), prostate cancer-specific mortality (PCSM), and overall mortality. MATERIALS
      AND METHODS: We retrospectively analyzed 2818 patients who underwent
      brachytherapy +/- external beam radiation therapy (EBRT) +/- androgen deprivation
      therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA
      failure at a median time of 3.25 years. Patients were stratified to early vs.
      late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in
      univariate/multivariate analyses for freedom from DM, cause-specific survival
      (CSS), and overall survival (OS). RESULTS: Among patients with PSA failures, 69
      (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other
      causes. Patients with rapid PSA failures demonstrated increased rates of DM,
      PCSM, and overall mortality, despite higher total BED and longer ADT. In
      multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR)
      for DM was 3.92 (95% CI: 2.34-6.55; p=0.000); HR for PCSM was 2.79 (95% CI: 1.45
      5.38; p=0.002); and HR for overall mortality was 2.28 (95% CI: 1.50-3.48;
      p=0.000). CONCLUSION: Early PSA failure following radiation is a poor prognostic
      factor, as it is associated with increased DM, PCSM, and overall mortality.

PMID- 24299970
TI  - Effects of probiotics on the recurrence of bacterial vaginosis: a review.
AB  - OBJECTIVE: Bacterial vaginosis (BV) is a common cause of genital discomfort in
      women in reproductive ages, which causes many complications. Bacterial vaginosis
      is usually treated by metronidazole and clindamycin. However, this protocol does
      not prevent its recurrence, which is a main complaint of the patients. The number
      of lactobacilli in the vagina of women with BV is significantly lower than that
      in healthy women. Hence, efforts have been made to normalize vaginal flora by
      oral or vaginal administration of lactobacilli. The objective of the present
      study was to review clinical evidences available regarding the efficacy of
      probiotics in the prevention and treatment of BV. MATERIALS AND METHODS:
      Published randomized controlled trials were searched in PubMed, Science Direct,
      and the Cochrane Database between 1990 and 2011. Search terms included bacterial
      vaginosis, urinary tract infection, lactobacillus, and probiotics. RESULTS:
      Orally consumed probiotics are believed to ascend to the vaginal tract after they
      are excreted from the rectum; vaginal administration allows for direct
      replacement of the probiotics for unhealthy vaginal microbiota and occupation of
      specific adhesion sites at the epithelial surface of the urinary tract, which
      consequently results in maintenance of a low pH and production of antimicrobial
      substances like acids and hydrogen peroxide. Receiving Lactobacillus acidophilus,
      Lactobacillus rhamnosus GR-1, and Lactobacillus fermentum RC-14 at a dose of at
      least 10 CFU/day for 2 months has been shown to present the patients with better
      results. CONCLUSIONS: Although the results of different studies are
      controversial, most studies have been in favor of the probiotics in the
      prevention or treatment of BV, and no adverse effects have been reported.
      Therefore, it may be helpful to recommend daily consumption of probiotic products
      to improve public health among women.

PMID- 24299968
TI  - Review of clinical brachytherapy uncertainties: analysis guidelines of GEC-ESTRO
      and the AAPM.
AB  - BACKGROUND AND PURPOSE: A substantial reduction of uncertainties in clinical
      brachytherapy should result in improved outcome in terms of increased local
      control and reduced side effects. Types of uncertainties have to be identified,
      grouped, and quantified. METHODS: A detailed literature review was performed to
      identify uncertainty components and their relative importance to the combined
      overall uncertainty. RESULTS: Very few components (e.g., source strength and
      afterloader timer) are independent of clinical disease site and location of
      administered dose. While the influence of medium on dose calculation can be
      substantial for low energy sources or non-deeply seated implants, the influence
      of medium is of minor importance for high-energy sources in the pelvic region.
      The level of uncertainties due to target, organ, applicator, and/or source
      movement in relation to the geometry assumed for treatment planning is highly
      dependent on fractionation and the level of image guided adaptive treatment. Most
      studies to date report the results in a manner that allows no direct reproduction
      and further comparison with other studies. Often, no distinction is made between
      variations, uncertainties, and errors or mistakes. The literature review
      facilitated the drafting of recommendations for uniform uncertainty reporting in
      clinical BT, which are also provided. The recommended comprehensive uncertainty
      investigations are key to obtain a general impression of uncertainties, and may
      help to identify elements of the brachytherapy treatment process that need
      improvement in terms of diminishing their dosimetric uncertainties. It is
      recommended to present data on the analyzed parameters (distance shifts, volume
      changes, source or applicator position, etc.), and also their influence on
      absorbed dose for clinically-relevant dose parameters (e.g., target parameters
      such as D90 or OAR doses). Publications on brachytherapy should include a
      statement of total dose uncertainty for the entire treatment course, taking into
      account the fractionation schedule and level of image guidance for adaptation.
      CONCLUSIONS: This report on brachytherapy clinical uncertainties represents a
      working project developed by the Brachytherapy Physics Quality Assurances System
      (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this
      report has been reviewed and approved by the American Association of Physicists
      in Medicine.

PMID- 24299971
TI  - Extracorporeal membrane oxygenation as a novel bridging strategy for acute right
      heart failure in group 1 pulmonary arterial hypertension.
AB  - Patients with group 1 pulmonary arterial hypertension (PAH) and decompensated
      right heart failure (RHF) were not previously considered for extracorporeal
      membrane oxygenation (ECMO) as bridge to transplantation (BTT) or bridge to
      recovery (BTR) because options were limited by long transplantation wait times
      and perceived inability to wean ECMO. In a retrospective review, we describe our
      center's multidisciplinary mechanical-medical approach to ECMO as a bridging
      therapy for PAH (2009-2012). Suitability for ECMO was determined using a defined
      algorithm. Six patients (age, 32 +/- 11 years) underwent mechanical-medical
      bridging. Two transplant-eligible patients underwent successful BTT. The four
      patients ineligible for transplantation underwent BTR with escalation of targeted
      medical therapies before weaning off ECMO. Three of four BTR patients survived to
      ECMO decannulation (duration, 12 +/- 7; range, 7-23 days). In this single
      institution experience, mechanical-medical BTT and BTR with ECMO and targeted PAH
      therapies were used as a novel treatment strategy to successfully manage acute
      RHF in PAH. 

PMID- 24299972
TI  - Innovative Free-range Resonant Electrical Energy Delivery system (FREE-D System)
      for a ventricular assist device using wireless power.
AB  - Technological innovation of a smaller, single moving part has an advantage over
      earlier large pulsatile ventricular assist devices (VADs) prone to mechanical
      failure. Drivelines limit the potential for extended patient survival durations
      with newer pumps and act as source for infection, increased morbidity,
      rehospitalizations, and reduced quality of life. The Free-range Resonant
      Electrical Energy Delivery (FREE-D) wireless power system uses magnetically
      coupled resonators to efficiently transfer power. We demonstrate the efficiency
      over distance of this system. The experimental setup consists of an
      radiofrequency amplifier and control board which drives the transmit resonator
      coil, and a receiver unit consisting of a resonant coil attached to a
      radiofrequency rectifier and power management module. The power management module
      supplies power to the axial pump, which was set at 9,600 rpm. To achieve a
      seamless wireless delivery in any room size, we introduced a third relay coil.
      This relay coil can be installed throughout a room, whereas a single relay coil
      could be built into a jacket worn by the patient, which would always be within
      range of the receive coil implanted in the patient's body. The power was
      delivered over a meter distance without interruptions or fluctuations with coil,
      rectifier, and regulator efficiency more than 80% and overall system efficiency
      of 61%. The axial pump worked well throughout the 8 hours of continuous
      operation. Having same setup on the opposite side can double the distance. A
      tether-free operation of a VAD can be achieved by FREE-D system in room-size
      distances. It has the potential to make the VAD therapy more acceptable from the
      patient perspective. 

PMID- 24299973
TI  - The effects of continuous and intermittent reduced speed modes on renal and
      intestinal perfusion in an ovine model.
AB  - The effects of the continuous-flow output on renal and intestinal
      microcirculation have not been extensively studied. To address this, the
      Heartware HVAD pump loaded with continuous and intermittent reduced speed (IRS)
      modes was implanted in four sheep and then operated at low and high speeds to
      mimic partial and complete unloading of the left ventricle. Then microsphere and
      positron emission tomography/computed tomography (PET/CT) studies were used to
      assess renal and intestinal tissue perfusion at various pump speeds and flow
      modes as compared with baseline (pump off). Arterial and venous oxygen (T02) and
      carbon dioxide (TCO2) contents were measured to assess changes in intestinal
      metabolism. Renal and intestinal regional blood flows did not produce any
      significant changes compared with baseline values in either continuous or IRS
      modes and speeds. The venous TO2 and TCO2 significantly increased in continuous
      and IRS modes and speeds compared with baseline. Our data suggested that renal
      and intestinal tissue perfusions were not adversely affected by continuous and
      IRS modes either in partial or complete unloading. Intestinal venous hyperoxia
      and increased TCO2 may be the evidence of intestinal arteriovenous shunting along
      with increased intestinal tissue metabolism. Longer-term studies are warranted in
      chronic heart failure models. 

PMID- 24299974
TI  - Ethical and legal aspects of noninvasive prenatal genetic diagnosis.
AB  - The new technology that will allow genetic testing of a fetus within the first
      trimester of pregnancy by isolating cell-free fetal DNA (cffDNA) in the mother's
      blood raises a range of ethical and legal issues. Considered noninvasive, this
      test is safe and reliable, and may avoid alternative genetic testing by
      amniocentesis or chorionic villus sampling, which risks causing spontaneous
      abortion. Ethical and legal issues of cffDNA testing will become more acute if
      testing expands to fetal whole-genome sequencing. Critical issues include the
      state of the science or diagnostic art; the appropriateness of offering the test;
      the implications of denying the test when it is available and appropriate;
      disclosure and counseling following test results; and management of patients'
      choices on acquiring test results. A challenge will be providing patients with
      appropriate counseling based on up-to-date genetic knowledge, and accommodating
      informed patients' legal choices. 

PMID- 24299975
TI  - Drotaverine to improve progression of labor among nulliparous women.
AB  - OBJECTIVE: To reevaluate the role of the antispasmodic drug drotaverine in
      shortening the length of the active first stage of labor among nulliparous women.
      METHODS: In a randomized, double-blind, placebo-controlled trial, 422 young
      nulliparous women admitted to Ain-shams University Maternity Hospital, Cairo,
      Egypt, in spontaneous labor were initially enrolled between May and December
      2012. Drotaverine hydrochloride (40mg) or placebo was given at the start of the
      active phase of labor and then repeated every 2hours (maximum 3 doses). All
      participants were consistently managed in accordance with the local institutional
      intrapartum protocol. The primary outcome was the rate of cervical dilation.
      RESULTS: After excluding women who delivered by cesarean, data were analyzed from
      320 women. There was a significant difference in post-treatment labor pain
      scores, duration of the active phase of labor, and rate of cervical dilatation
      between the 2 groups (P<0.001 for all). There was no difference in maternal
      adverse effects. Kaplan-Meier survival analysis showed a greater probability of
      faster delivery among patients treated by drotaverine hydrochloride (log rank
      test; P<0.001). CONCLUSION: Drotaverine hydrochloride was used effectively and
      safely to shorten the duration of the first stage of labor among nulliparous
      women with active spontaneous labor. ClinicalTrials.gov: NCT01639027.

PMID- 24299976
TI  - The essential role of the phosphorylated pathway of serine biosynthesis in
      Arabidopsis.
AB  - In plants, 3 different pathways of serine biosynthesis have been described: the
      Glycolate pathway, which is associated with photorespiration, and 2 non
      photorespiratory pathways, the Glycerate and the Phosphorylated pathways. The
      Phosphorylated Pathway of Serine Biosynthesis (PPSB) has been known since the
      1950s, but has been studied relatively little, probably because it was considered
      of minor significance as compared with the Glycolate pathway. In the associated
      study (1), we described for the first time in plants the in vivo functional
      characterization of the PPSB, by targeting the phosphoserine phosphatase (PSP1),
      the last enzyme of the pathway. Following a gain- and loss-of-function approach
      in Arabidopsis, we provided genetic and molecular evidence for the essential role
      of PSP1 for embryo and pollen development, and for proper root growth. A
      metabolomics study indicated that the PPSB affects glycolysis, the Krebs cycle,
      and the biosynthesis of several amino acids, which suggests that this pathway is
      an important link connecting metabolism and development. The mechanisms
      underlying the essential functions of PSP1 are discussed. 

PMID- 24299977
TI  - Characterization of virus-like particles in GARDASIL(r) by cryo transmission
      electron microscopy.
AB  - Cryo-transmission electron microscopy (cryoTEM) is a powerful characterization
      method for assessing the structural properties of biopharmaceutical
      nanoparticles, including Virus Like Particle-based vaccines. We demonstrate the
      method using the Human Papilloma Virus (HPV) VLPs in GARDASIL(r). CryoTEM,
      coupled to automated data collection and analysis, was used to acquire images of
      the particles in their hydrated state, determine their morphological
      characteristics, and confirm the integrity of the particles when absorbed to
      aluminum adjuvant. In addition, we determined the three-dimensional structure of
      the VLPs, both alone and when interacting with neutralizing antibodies. Two modes
      of binding of two different neutralizing antibodies were apparent; for HPV type
      11 saturated with H11.B2, 72 potential Fab binding sites were observed at the
      center of each capsomer, whereas for HPV 16 interacting with H16.V5, it appears
      that 60 pentamers (each neighboring 6 other pentamers) bind five Fabs per
      pentamer, for the total of 300 potential Fab binding sites per VLP. 

PMID- 24299978
TI  - Study on interaction between palladium(II)-Linezolid chelate with eosin by
      resonance Rayleigh scattering, second order of scattering and frequency doubling
      scattering methods using Taguchi orthogonal array design.
AB  - Linezolid reacted with palladium to form 1:1 binary cationic chelate which
      further reacted with eosin dye to form 1:1 ternary ion association complex at pH
      4 of Walpole's acetate buffer in the presence of methyl cellulose. As a result
      not only absorption spectra were changed but Resonance Rayleigh Scattering (RRS),
      Second-order Scattering (SOS) and Frequency Doubling Scattering (FDS) intensities
      were greatly enhanced. The analytical wavelengths of RRS, SOS and FDS
      (lambdaex/lambdaem) of ternary complex were located at 538 nm/538nm, 240 nm/480
      nm and 660 nm/330 nm, respectively. The linearity range for RRS, SOS and FDS
      methods were 0.01-0.5 MUg mL(-1), 0.1-2 MUg mL(-1) and 0.2-1.8 MUg mL(-1),
      respectively. The sensitivity order of three methods was as RRS>SOS>FDS. Accuracy
      of all methods were determined by recovery studies and showed recovery between
      98% and 102%. Intraday and inter day precision were checked for all methods and
      %RSD was found to be less than 2 for all methods. The effects of foreign
      substances were tested on RRS method and it showed the method had good
      selectivity. For optimization of process parameter, Taguchi orthogonal array
      design L8(2(4)) was used and ANOVA was adopted to determine the statistically
      significant control factors that affect the scattering intensities of methods.
      The reaction mechanism, composition of ternary ion association complex and
      reasons for scattering intensity enhancement was discussed in this work.

PMID- 24299979
TI  - Penetration of three transmembrane segments of Slc11a1 in lipid bilayers.
AB  - Slc11a1 is a divalent metal cation transporter with 12 putative transmembrane
      domains (TM) and plays a role in host defense. In present work, we investigated
      the secondary structure and topology of the peptides associated to Slc11a1-TM2,
      TM3 and TM4 (wildtype peptides and function-relating mutants) in the phospholipid
      vesicles (DMPC, DMPG and their mixtures) using circular dichroism, fluorescence
      spectroscopy and differential scanning calorimetry. We found that TM3 is
      obviously different in secondary structure and topology from TM2 to TM4 in the
      lipid membranes. The peptide TM3 is less structured and embedded in the lipid
      membranes less deeply than TM2 and TM4 at pH 5.5 and 7. The insertion position of
      TM3 in the lipid membranes is adjusted by pH, more deeply at more acidic pH
      environment, whereas the locations of TM2 and TM4 in the lipid membranes are less
      changed with pH. The E139A substitution of TM3 significantly impairs the pH
      dependence of the buried depth of TM3 and causes a pronounced increase in
      helicity in all DMPG-containing lipid vesicles at pH 5.5 and 7 and in DMPC at pH
      4. In contrast, TM2 and TM4 are similar in topology. The G169D mutation has
      little effect on the topological arrangement of TM4 in membranes. The property of
      headgroups of the phospholipids has an effect on the secondary structure and
      topology of the peptides. All peptides could be structured with more helicity and
      embedded more deeply in DMPG-containing lipid vesicles than in DMPC membrane at
      pH 5.5 and 7. 

PMID- 24299980
TI  - Ca(1-x-y)Dy(x)K(y)WO4: a novel near UV converting phosphor for white light
      emitting diode.
AB  - A series of Dy(3+)/K(+) doped calcium tungstate phosphors were synthesized by
      solid state reaction method. The crystal structure, surface morphology, chemical
      composition and photoluminescence properties of the prepared phosphors were
      investigated. The luminescence decay curves of doped/codoped phosphors were
      recorded. The X-ray diffraction analysis shows that the phosphors are of
      tetragonal structure. SEM studies confirm the particle size in the micro-meter
      (MUm) range. The photoluminescence results indicate that these phosphors could be
      efficiently excited by the near-ultraviolet radiation which causes the emission
      in the blue and yellow regions. The white light was achieved by tailoring this
      yellow to blue ratio varying the Dy(3+)/K(+) dopant concentration. The quality of
      emitted white light was checked by calculating different CIE parameters of these
      phosphors. Decay kinetics studies confirms the life time of activator ions in
      micro-second (MUs) range. 

PMID- 24299981
TI  - Molecular modeling and spectroscopic studies on the interaction of the chiral
      drug venlafaxine hydrochloride with bovine serum albumin.
AB  - This study was designed to examine the interaction of racemic antidepressant drug
      "S,R-venlafaxine hydrochloride (VEN)" with bovine serum albumin (BSA) under
      physiological conditions. The mechanism of interaction was studied by
      spectroscopic techniques combination with molecular modeling. Stern-Volmer
      analysis of fluorescence quenching data shows the presence of the static
      quenching mechanism. The thermodynamic parameters indicated that the hydrogen
      bonding and weak van der Waals interactions are the predominant intermolecular
      forces stabilizing the complex. The number of binding sites (n) was calculated.
      Through the site marker competitive experiment, VEN was confirmed to be located
      in subdomain IIIA of BSA. The binding distance (r=4.93 nm) between the donor BSA
      and acceptor VEN was obtained according to Forster's non-radiative energy
      transfer theory. According to UV-vis spectra and CD data binding of VEN leaded to
      conformational changes of BSA. Molecular docking simulations of S and R-VEN
      revealed that both isomers have similar interaction and the same binding sites,
      from this point of view S and R isomers are equal.

PMID- 24299982
TI  - An uniform DBD plasma excited by bipolar nanosecond pulse using wire-cylinder
      electrode configuration in atmospheric air.
AB  - In this study, a bipolar nanosecond pulsed power supply with 15 ns rising time is
      employed to generate an uniform dielectric barrier discharge using the wire
      cylinder electrode configuration in atmospheric air. The images, waveforms of
      pulse voltage and discharge current, and the optical emission spectra of the
      discharges are recorded. The rotational and vibrational temperatures of plasma
      are determined by comparing the simulated spectra with the experimental spectra.
      The effects of pulse peak voltage, pulse repetition rate and quartz tube diameter
      on the emission intensities of N2 (C(3)Piu->B(3)Pig, 0-0) and N2(+)B(2)Sigmau(+)
      >X(2)Sigmag(+),0-0 and the rotational and vibrational temperatures have been
      investigated. It is found that the uniform plasma with low gas temperature can be
      obtained, and the emission intensities of N2 (C(3)Piu->B(3)Pig, 0-0) and
      N2(+)B(2)Sigmau(+)->X(2)Sigmag(+),0-0 rise with increasing the pulse peak voltage
      and pulse repetition rate, while decrease as the increase of quartz tube
      diameter. In addition, under the condition of 28 kV pulse peak voltage, 150 Hz
      pulse repetition rate and 7 mm quartz tube diameter, the plasma gas temperature
      is determined to be 330 K. The results also indicate that the plasma gas
      temperature keep almost constant when increasing the pulse peak voltage and pulse
      repetition rate but increase with the increase of the quartz tube diameter.

PMID- 24299983
TI  - Synthesis and enhancement of photocatalytic activities of ZnO by silver
      nanoparticles.
AB  - Herein, we reports synthesis, characterization and photocatalytic degradation of
      Rhodamine B under natural sunlight using zinc oxide and Ag-ZnO composite. Zinc
      oxide nanoparticles were prepared by simple wet chemical method using ethanol
      water mixture. Ag-ZnO composite was prepared in two steps by dispersing
      synthesized ZnO in silver nitrate solution and subsequently reducing it with
      Ocimum tenuiflorum leaves extract as bioreducing agent. The synthesized bare zinc
      oxide and Ag-ZnO composite was characterized by various techniques like XRD, DRS,
      FE-SEM, TEM, SAED, PSD, Zeta potentials, etc. Zinc oxide being wide band gap
      material can absorbs UV light from solar spectrum which is only 5% so is not
      efficient material for dye degradation under sunlight. The absorption of visible
      light was increased by preparing the Ag-ZnO composite. The enhancement in
      photocatalytic activities of Ag-ZnO composite was observed than bare ZnO. This
      enhancement is due to shift of absorption edge of ZnO in visible region and
      decrease in band gap. 

PMID- 24299984
TI  - Synthesis, characterization and the interaction of some new water-soluble metal
      Schiff base complexes with human serum albumin.
AB  - Some new water-soluble Schiff base complexes of Na2[M(L)(H2O)n]; (M=Zn, Cu, Ni,
      Mn) with a new water-soluble Schiff base ligand where L denotes an asymmetric
      N2O2 Schiff base ligands; N,N'-bis(5-sulfosalicyliden)-3,4-diaminobenzophenone (5
      SO3-3,4-salbenz) were synthesized and characterized. The formation constants of
      the water soluble Schiff base complexes were calculated by Ketelaar's equation.
      The theoretical molecular structure for the complexes was computed by using the
      HF method and the 6-311G basis set. The mechanism of binding of Na2[M(L)(H2O)n]
      with human serum albumin (HSA) was studied by fluorescence spectroscopic
      technique. The results of fluorescence titration showed that the intrinsic
      fluorescence of HSA was quenched by the complexes; which was rationalized in
      terms of the dynamic quenching mechanism. The values of Stern-Volmer constants,
      quenching rate constants, binding constants, binding sites and average
      aggregation number of HSA have been determined. The thermodynamic parameters,
      were calculated by van't Hoff equation, indicate that the binding is entropy
      driven and enthalpically disfavored. Based on the Forster theory of non-radiation
      energy transfer, the efficiency of energy transfer and the distance between the
      donor (Trp residues) and the acceptor (complex) were obtained. Finally, the
      growth inhibitory effects of the complexes toward the K562 cancer cell line were
      measured. 

PMID- 24299985
TI  - Vibrational spectra, molecular structure, NBO, UV, NMR, first order
      hyperpolarizability, analysis of 4-Methoxy-4'-Nitrobiphenyl by density functional
      theory.
AB  - In this study, geometrical optimization, spectroscopic analysis, electronic
      structure and nuclear magnetic resonance studies of 4-Methoxy-4'-Nitrobiphenyl
      (abbreviated as 4M4'NBPL) were investigated by utilizing HF and DFT/B3LYP with 6
      31G(d,p) as basis set. The equilibrium geometry, vibrational wavenumbers and the
      first order hyperpolarizability of the 4M4'NBPL have been calculated with the
      help of density functional theory computations. The FT-IR and FT-Raman spectra
      were recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively.
      Natural Bond Orbital (NBO) analysis is also used to explain the molecular
      stability. The UV-Vis absorption spectra of the title compound dissolved in
      chloroform were recorded in the range of 200-800 cm(-1). The HOMO-LUMO energy gap
      explains the charge interaction taking place within the molecule. Good
      correlation between the experimental (1)H and (13)C NMR chemical shifts in
      chloroform solution and calculated GIAO shielding tensors were found. The dipole
      moment, linear polarizability and first order hyperpolarizability values were
      also computed. The linear polarizability and first order hyperpolarizability of
      the studied molecule indicate that the compound is a good candidate of nonlinear
      optical materials. The chemical reactivity and thermodynamic properties of
      4M4'NBPL at different temperature are calculated. In addition, molecular
      electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis were
      investigated using theoretical calculations.

PMID- 24299986
TI  - Association between C-reactive protein level and echocardiography assessed left
      ventricular function in first ST-segment elevation myocardial infarction patients
      who underwent primary coronary intervention.
AB  - BACKGROUND: An elevated C-reactive protein (CRP) level is associated with adverse
      outcomes in patients with acute myocardial infarction (AMI). Although CRP levels
      have been shown to be associated with left ventricular (LV) systolic function and
      remodeling in AMI, little is known about their relation to early LV diastolic
      function. METHODS: We retrospectively studied 173 consecutive patients <75 years
      of age with first ST-segment elevation MI (STEMI) that was treated by primary
      percutaneous coronary intervention (PPCI). They had presented within 24h of chest
      pain onset and their CRP levels were determined within 6h of hospital admission.
      They all underwent echocardiography within 3 days of admission and were
      stratified by CRP tertiles. RESULTS: The cut-off points for the CRP tertiles were
      <2.6 mg/L, 2.6-7.9 mg/L, and >7.9 mg/L. Patients with higher CRP levels had a
      significantly higher mean mitral inflow E wave velocity (68 +/- 16 cm/s vs 77 +/-
      19 cm/s vs 76 +/- 17 cm/s; p=0.02), a higher E/average e' (8.9 +/- 1.9 vs 9.8 +/-
      2.8 vs 10.4+/-3.2; p=0.02), and a higher systolic pulmonary artery pressure (27
      +/- 6 mmHg vs 30 +/- 8 mmHg vs 32 +/- 10 mmHg; p=0.04). Elevated CRP levels were
      associated with more advanced diastolic dysfunction than normal CRP levels
      (p=0.04). The admission CRP level was an independent predictor of average E/e'
      ratio (multivariate analysis). CONCLUSION: Admission CRP levels are associated
      with echocardiographic parameters of elevated LV filling pressure in patients
      with STEMI treated with PPCI.

PMID- 24299987
TI  - Intracellular recording, sensory field mapping, and culturing identified neurons
      in the leech, Hirudo medicinalis.
AB  - The freshwater leech, Hirudo medicinalis, is a versatile model organism that has
      been used to address scientific questions in the fields of neurophysiology,
      neuroethology, and developmental biology. The goal of this report is to
      consolidate experimental techniques from the leech system into a single article
      that will be of use to physiologists with expertise in other nervous system
      preparations, or to biology students with little or no electrophysiology
      experience. We demonstrate how to dissect the leech for recording intracellularly
      from identified neural circuits in the ganglion. Next we show how individual
      cells of known function can be removed from the ganglion to be cultured in a
      Petri dish, and how to record from those neurons in culture. Then we demonstrate
      how to prepare a patch of innervated skin to be used for mapping sensory or motor
      fields. These leech preparations are still widely used to address basic
      electrical properties of neural networks, behavior, synaptogenesis, and
      development. They are also an appropriate training module for neuroscience or
      physiology teaching laboratories. 

PMID- 24299988
TI  - Species assemblage patterns around a dominant emergent tree are associated with
      drought resistance.
AB  - Water availability has long been recognized as an important driver of species
      distribution patterns in forests. The conifer Agathis australis (D. Don) Lindl.
      (kauri; Araucariaceae) grows in the species-rich forests of northern New Zealand.
      It is accompanied by distinctive species assemblages, and during summer the soil
      beneath A. australis is often significantly drier than soils beneath surrounding
      broadleaved angiosperm canopy species. We used a shade house dry-down experiment
      to determine whether species that grow close to A. australis differed in drought
      tolerance physiology compared with species that rarely grow close to A.
      australis. Stomatal conductance (g(s)) was plotted against leaf water potential
      (psi) to identify drought tolerance strategies. Seedlings of species that occur
      in close spatial association with A. australis (including A. australis seedlings)
      were most resistant to drought stress, and all displayed a drought avoidance
      strategy of either declining gs to maintain psi or simultaneous declines in g(s)
      and psi. The species not commonly occurring beneath A. australis, but abundant in
      the surrounding forest, were the most drought-sensitive species and succumbed
      relatively quickly to drought-induced mortality with rapidly declining gs and psi
      values. These results were confirmed with diurnal measurements of g(s) and
      assimilation rates throughout the day, and leaf wilting analysis. We conclude
      that the varied abilities of the species to survive periods of drought stress as
      seedlings shapes the composition of the plant communities beneath A. australis
      trees. Furthermore, forest diversity may be impacted by climate change as the
      predicted intensification of droughts in northern New Zealand is likely to select
      for drought-tolerant species over drought-intolerant species.

PMID- 24299989
TI  - Development of a highly sensitive, high-throughput assay for glycosyltransferases
      using enzyme-coupled fluorescence detection.
AB  - Glycosyltransferases catalyze transfer of sugar moieties from activated donor
      molecules to specific acceptor molecules, forming glycosidic bonds.
      Identification of selective modulators of glycosyltransferases is important both
      to provide new tools for investigating pathophysiological roles of glycosylation
      reactions in cells and tissues, and as new leads in drug discovery. Here we
      describe a universal enzyme-coupled fluorescence assay for glycosyltransferases,
      based on quantification of nucleotides produced in the glycosyl transfer
      reaction. GDP, UDP, and CMP are phosphorylated with nucleotide kinase in the
      presence of excess ATP, generating ADP. Via coupled enzyme reactions involving
      ADP-hexokinase, glucose-6-phosphate dehydrogenase, and diaphorase, the ADP is
      utilized for conversion of resazurin to resorufin, which is determined by
      fluorescence measurement. The method was validated by comparison with an HPLC
      method, and employed to screen the LOPAC1280 library for inhibitors in a 384-well
      plate format. The assay performed well, with a Z'-factor of 0.80. We identified
      12 hits for human galactosyltransferase B4GALT1 after elimination of false
      positives that inhibited the enzyme-coupled assay system. The assay components
      are all commercially available and the reagent cost is only 2 to 10 US cents per
      well. This method is suitable for low-cost, high-throughput assay of various
      glycosyltransferases and screening of glycosyltransferase modulators. 

PMID- 24299990
TI  - A graphene screen-printed carbon electrode for real-time measurements of
      unoccupied active sites in a cellulase.
AB  - Cellulases hydrolyze cellulose to soluble sugars and this process is utilized in
      sustainable industries based on lignocellulosic feedstock. Better analytical
      tools will be necessary to understand basic cellulase mechanisms, and hence
      deliver rational improvements of the industrial process. In this work we describe
      a new electrochemical approach to the quantification of the populations of enzyme
      that are respectively free in the aqueous bulk, adsorbed to the insoluble
      substrate with an unoccupied active site or threaded with the cellulose strand in
      the active tunnel. Distinction of these three states appears essential to the
      identification of the rate-limiting step. The method is based on disposable
      graphene-modified screen-printed carbon electrodes, and we show how the temporal
      development in the concentrations of the three enzyme forms can be derived from a
      combination of the electrochemical data and adsorption measurements. The approach
      was tested for the cellobiohydrolase Cel7A from Hypocrea jecorina acting on
      microcrystalline cellulose, and it was found that the threaded enzyme form
      dominates for this system while adsorbed enzyme with an unoccupied active site
      constitutes less than 5% of the population. 

PMID- 24299992
TI  - MR Imaging of Hippocampal Sulcus Remnant: Age-Related Differences.
AB  - The hippocampal sulcus remnant (HSR) is often observed at the medial temporal
      lobe on MR images. In the present study, we made a retrospective assessment of
      the frequency and age-related differences in HSR in routine brain MR examinations
      of 1000 patients, 494 females and 506 males. Cases with one or several spots that
      were hypointense on T1-weighted and FLAIR images and hyperintense on T2-weighted
      images were defined as positive for HSR. Abnormal spots with the same intensity
      as cerebrospinal fluid were observed in 210 out of 506 males and in 193 out of
      494 females. No significant sex-related differences were observed in the
      frequency of HSR. The HSR was seen more frequently with age in both males and
      females. Patients with hypertension had a significantly higher frequency of HSR. 

PMID- 24299991
TI  - Analysis of plant nucleotide sugars by hydrophilic interaction liquid
      chromatography and tandem mass spectrometry.
AB  - Understanding the intricate metabolic processes involved in plant cell wall
      biosynthesis is limited by difficulties in performing sensitive quantification of
      many involved compounds. Hydrophilic interaction liquid chromatography is a
      useful technique for the analysis of hydrophilic metabolites from complex
      biological extracts and forms the basis of this method to quantify plant cell
      wall precursors. A zwitterionic silica-based stationary phase has been used to
      separate hydrophilic nucleotide sugars involved in cell wall biosynthesis from
      milligram amounts of leaf tissue. A tandem mass spectrometry operating in
      selected reaction monitoring mode was used to quantify nucleotide sugars. This
      method was highly repeatable and quantified 12 nucleotide sugars at low femtomole
      quantities, with linear responses up to four orders of magnitude to several
      100pmol. The method was also successfully applied to the analysis of purified
      leaf extracts from two model plant species with variations in their cell wall
      sugar compositions and indicated significant differences in the levels of 6 out
      of 12 nucleotide sugars. The plant nucleotide sugar extraction procedure was
      demonstrated to have good recovery rates with minimal matrix effects. The
      approach results in a significant improvement in sensitivity when applied to
      plant samples over currently employed techniques. 

PMID- 24299993
TI  - Imaging of Rathke's Cleft Cysts: Criteria for a Differential Diagnosis.
AB  - Rathke's cleft cysts are a congenital disorder of the pituitary gland and derive
      from abnormalities of the development of the adenohypophisis. The variability of
      the MRI signal of Rathke's cleft cyst hampers the differential diagnosis with the
      other cystic lesions of the pituitary gland. Nevertheless a comparison between
      the various findings reported from by author we reviewed indicates that a
      description of useful criteria for a differential diagnosis is possible. We
      suggest that the mean age at onset, the symptoms, the magnetic signal intensity,
      the location within the gland, the relations with the surrounding structures and
      the behaviour after contrast injection should always be considered in the
      diagnostic work-up of Rathke 's cleft cysts. There is no consensus in the
      literature on the correct therapeutic protocol. We suggest following up a small
      asymptomatic Rathke's cleft cyst (except mucoid cysts) because they do not
      generally enlarge. Surgery is instead the gold standard for symptomatic Rathke's
      cleft cysts, large Rathke's cleft cysts and mucoid Rathke's cleft cysts. Mucoid
      Rathke's cleft cysts, even when small, may cause an intense pituitary
      inflammation which could lead to irreversible endocrine dysfunction. 

PMID- 24299994
TI  - Apparent diffusion coefficient is increased in children with tuberous sclerosis
      complex personal experience and review of the literature.
AB  - Diffusion-weighted imaging (DWI) provides information on tissue integrity and
      shows increased sensivity in detecting brain white matter disease compared to
      traditional T2-weighted MRI. We compared apparent diffusion coefficient (ADC)
      values in brain lesions and normal appearing white matter (NAWM) in patients with
      tuberous sclerosis complex (TSC) to normal brain tissue in the control group. MRI
      and DWI were performed in 14 patients with TSC (age range 7-16 years) and in 18
      age-matched normal control subjects. ADC values measured from 44 supratentorial
      cortical tubers, 37 white matter lesions, 80 NAWM were compared to those in
      control subjects. Statistical analysis was performed using Kruskal-Wallis and
      Mann-Whitney U tests. The highest ADCs were measured in cortical tubers (mean
      ADC, 1.24*10-3 mm(2)/s), followed in descending order by WM lesions (mean ADC,
      1.07*10-3 mm(2)/s), NAWM (mean ADC, 0.83*10-3 mm(2)/s). We found a significant
      difference in ADC values of gray, WM lesions and NAWM in TSC patients compared to
      the control group (p<0,0001). Elevated ADC values in NAWM in TSC patients may be
      caused by subtle depletion of myelin sheaths and looseness of structures within
      the brain parenchyma due to underlying migration disorders. 

PMID- 24299995
TI  - Diffusion-weighted MRI of van der knaap leukoencephalopathy. A case report.
AB  - An eight-month-old girl was admitted with signs and symptoms of deterioration of
      motor functions. Cranial MRI demonstrated widespread bilateral increased signal
      of cerebral white matter on T2-weighted images accompanying bilateral cyst-like
      structures at the subcortical location of frontal and parietal lobes and
      bilateral cysts at the temporal lobes. On diffusion MRI, increased diffusion with
      high ADC values were detected. The patient was diagnosed as an MLC subtype of Van
      Der Knaap Leukoencephalopathy with clinical and radiological findings. Cranial
      MRI and diffusion MRI findings are discussed in this paper. 

PMID- 24299996
TI  - MR Imaging in Anderson-Fabry Disease: What Are We Expected to Find?
AB  - Anderson-Fabry disease (FD) is a genetic disorder of glycosphingolipid metabolism
      that can involve CNS and is easily detectable with MRI. We reviewed 32 MRI
      performed in ten patients to detect an eventual specific pattern of the disease
      suggesting that finding vascular lesions in young adults must be addressed to
      diagnose different pathologies including FD. 

PMID- 24299997
TI  - Optic chiasm involvement secondary to herpetic encephalitis. A case report.
AB  - Herpes simplex (HSV) encephalitis is one of the most common central nervous
      system (CNS) viral infections in adults. Early diagnosis is essential for
      treatment. We describe the case of a 70-year-old man who reported sudden
      bilateral reduction of visus. Four days after admission the patient showed high
      fever, followed the next day by a generalised convulsive crisis and coma. A first
      magnetic resonance imaging (MRI) showed no alterations, whereas the second showed
      the usual patterns of HSV encephalitis. With a clinical suspicion of herpetic
      encephalitis an intravenous therapy with acyclovir was established. The diagnosis
      of herpetic encephalitis was confirmed by cerebrospinal fluid (CSF) detection of
      herpes simplex DNA sequences. A further ten days later we performed a third MRI,
      demonstrating the typical pattern of HSV encephalitis and an increase in size and
      signal of the optic chiasm. 

PMID- 24299998
TI  - CT-Cisternography in Post-Surgical CSF Rhinorrhea. A Report of Two Cases.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is a dangerous problem. CSF rhinorrhea
      implies an abnormal communication between the subarachnoid space and the nasal
      cavity, with subsequent leakage of CSF through the anterior nasal apertures.
      requiring surgical repair. Imaging techniques have evolved from conventional
      cranial radiography to polytomography, thin-section computed tomography (CT) and
      intrathecal water-soluble iodinated contrast agent-enhanced CT cisternography. We
      present two cases of post-surgical CSF rhinorrhea in which the best diagnostic
      findings were obtained by CT cisternography. 

PMID- 24299999
TI  - Efficacy of in vivo 31Phosphorus Magnetic Resonance Spectroscopy in
      Differentiation and Staging of Adult Human Brain Tumors.
AB  - The aim of this study was to evaluate the efficacy of (31)P magnetic resonance
      spectroscopy ((31)P-MRS) in the differentiation and staging of brain tumors.
      Fifteen volunteers and 44 patients with brain tumors (14 meningiomas, 13 low- and
      17 high-grade gliomas) were prospectively evaluated by (31)P-MRS. The pH
      (r=0.493, p<0.001), [Mg(+2)] (r=0.850, p<0.001) PME/alpha-ATP (r=0.776, p<0.001),
      PDE/alpha-ATP (r=-0.569, p<0.001) and (PCr+beta-ATP)/Pi ratios were well
      correlated with tumor differentiation. High-grade gliomas had significantly
      higher pH (r=0.912, p<0.001) and [Mg(+2)] (r=0.855, p<0.001) and PME/alpha-ATP
      (r=0.894, p<0.001) ratio, and lower PCr/alpha-ATP (r=-0.959, p<0.001), Pi/alpha
      ATP (r=-0.788, p<0.001) and PDE/alpha-ATP ratios (r=-0.968, p<0.001) than those
      of low-grade gliomas. Changes in (31)P-MRS parameters by the degree of malignancy
      are good indicators of increased anaerobic metabolism and hypoxia of tumoral
      tissue to compensate intratumoral energy deficiency. (31)P-MRS parameters are
      very useful for grading and differentiation of brain tumors. 

PMID- 24300000
TI  - Cerebral MR Perfusion Imaging Analysis of Peritumoral Tissue.
AB  - Highly malignant gliomas have an infiltrating growth making it impossible to
      establish the exact limits of the lesion with magnetic resonance images after
      contrast medium administration because the peripheral component of the lesion
      does not enhance. On the contrary, cerebral metastases have an expansive growth
      and therefore lack a peripheral component beyond the enhanced area. In some cases
      the MR perfusional technique can demonstrate neoplastic tissue even with little
      damage to the brain-blood barrier and therefore with no enhancement. Our study
      aimed to estimate in which cases the MR perfusion technique will characterize
      peripheral neoplastic tissue that fails to enhance in gliomas in order to make a
      differential diagnosis between gliomas and metastases. We studied 60 tumours in
      53 patients with MR perfusion and conventional sequences. We evaluated the
      presence of hyperperfused tissue in CBV maps outside the enhanced area after
      contrast administration and estimated the tumoral tissue CBV. None of the
      metastases (24 cases) had hyperperfused peritumoural tissue which was present
      instead in 22/36 gliomas (infiltrating aspect in CBV maps). Moreover all the
      gliomas with infiltrating aspect had CBV values of the solid component of the
      lesion higher than gliomas with a non infiltrating aspect with a threshold value
      between 4.4 and 6.3. It was therefore possible to characterize 22 gliomas with
      infiltrating aspect in the perfusion maps and with CBV values higher than the
      threshold value. In addition, 17 metastases with a non infiltrating aspect were
      characterized with CBV values higher than the threshold. Fourteen gliomas and
      seven metastases both with a non infiltrating aspect in the perfusion maps and
      with CBV values below the threshold were not characterized. In conclusion, MR
      perfusion succeeded in characterizing 39 lesions out of 60. 

PMID- 24300001
TI  - Small cell carcinoma of the lung presenting with ocular metastasis. A case
      report.
AB  - Metastasis to the eye is rare but it may be the presenting symptom. Therefore
      awareness of the radiological findings of metastasis may aid in establishing its
      diagnosis. Here we report an ocular metastasis of small cell carcinoma of the
      lung presenting with pulmonary and ocular manifestations. 

PMID- 24300002
TI  - Diffusion-Weighted Magnetic Resonance Imaging and ADC Maps in the Diagnosis of
      Intracranial Cystic or Necrotic Lesions. A Retrospective Study on 49 Patients.
AB  - This study evaluated the usefulness of diffusion-weighted (DW) magnetic resonance
      imaging (MRI) and ADC maps in the differential diagnosis of brain abscesses from
      cystic or necrotic neoplasms. MR images of 49 patients with 54 lesions were
      examined retrospectively. All patients underwent conventional MRI and DWI, and
      ADC values were calculated by placing ROIs of 30 mm(2) manually over the cystic
      part of the lesions. On DWI, all cystic portions of abscesses were hyperintense.
      Mean ADC values were 0.48*10 mm(2)/s (range 0.41-0.54*10 mm/s) for pyogenic
      abscesses, 0.73*10 mm(2)/s (range 0.65-0.91*10 mm/s) for mycotic abscesses and
      0.6 mm(2)/s for Nocardia abscess. Cystic areas appeared hypointense on DWI in
      33/44 tumours (mean value ADC 1.96 mm(2)/s). Eleven tumours (11/44) appeared
      hyperintense on DWI: eight metastases from lung cancer (mean ADC value 0.86
      mm(2)/s, range 0.75-1.2 mm(2)/s), two GBMs (mean 0.7 mm(2)/s, range 0.67-0.76
      mm(2)/s) and one anaplastic astrocytoma (ADC value 1.24 mm(2)/s). ADC values may
      help in differentiating pyogenic abscess from brain tumors or metastatic lesions.

PMID- 24300003
TI  - Extremely low-frequency pulsed magnetic fields and multiple sclerosis: effects on
      neurotransmission alone or also on immunomodulation? Building a working
      hypothesis.
AB  - This paper outlines the current state of knowledge on the pathology and treatment
      of multiple sclerosis (MS) and critically analyses the vast clinical experience
      of Sandyk in the use of pulsed magnetic fields of 5 Hz at 7.5 pT to treat many
      symptoms of MS. A complete regression of symptoms, or at least a major
      improvement, is sometimes so rapid as to suggest that ELF fields exert a greater
      effect on axonal and synaptic neurotransmission than on the processes leading to
      demyelination. Pulsed magnetic fields of 50-100 Hz and a few mT (whose flux
      intensity is 10(9) times greater than that of the fields used by Sandyk) have
      been seen to induce profound morphological changes (the Marinozzi effect) in the
      plasma membrane of several cell types, including Raji human lymphoblastoid cells.
      These observations underlie the author's hypothesis on the possible use of such
      fields in the treatment of MS. Indeed, these fields should induce the functional
      arrest of the cells (B- and T-lymphocytes, macrophages, microglia, dendritic
      cells) of the MS plaque, thereby providing an "electromagnetic immunomodulatory
      boost" to the effects of drug therapy. To test this working hypothesis, it is
      suggested that preliminary experimental research be carried out to ascertain: 1)
      the Marinozzi effect in vivo; 2) the Marinozzi effect on microglia and dendritic
      cells; and 3) the duration of the membrane changes and their relaxation rate. ELF
      magnetic fields in the picotesla and millitesla ranges are aimed at improving
      neurotransmission and correcting local immune pathology, respectively. Both types
      of field might find application in the treatment of MS patients who no longer
      respond to or tolerate currently used drugs. 

PMID- 24300004
TI  - Traumatic retropharyngeal pseudomeningocele with atlanto-occipital dislocation in
      a neurologically intact patient.
AB  - Traumatic retropharyngeal pseudomeningoceles occur rarely, are associated with
      severe trauma, and have been reported in patients with significant neurologic
      deficits at presentation. We report the rare occurrence of a pseudomeningocele
      following a high-speed motor vehicle accident. Neurological examination showed
      the patient to be briskly following commands, with intact cranial nerve, motor,
      and sensory function. CT/MR imaging showed subarachnoid hemorrhage involving the
      interpeduncular cistern, a clivus fracture, a right occipital condyle fracture,
      an atlanto-occipital subluxation, aortic arch transection (stable and contained
      on CT angiogram), multiple rib fractures on the right side with associated
      pneumothorax, hemothorax and pulmonary contusions. His cervical spine was
      stabilized in a halo. He was subsequently managed in the intensive care unit and
      remained neurologically intact. A repeat MRI showed the interval development of a
      2*1.5 cm pseudomeningocele at the craniocervical junction medial to the left
      occipital condyle communicating with the left anterolateral aspect of the spinal
      canal. Traumatic pseudomeningoceles are associated with large deceleration forces
      at the time of injury and are usually associated with significant neurologic
      deficits at presentation. However, they can arise and give rise to symptoms in a
      delayed fashion in trauma patients who are neurologically intact at initial
      presentation. 

PMID- 24300005
TI  - Resection of orbital rhabdomyosarcoma in an infant with the aid of preoperative
      partial arterial embolization. A case report.
AB  - Since the introduction of non-invasive imaging techniques (CT, US, MRI), super
      selective cerebrospinal angiography has been playing a major role as a diagnostic
      tool as well as a therapeutic procedure prior to surgery or as an alternative.
      Surgical neuroangiography is currently a well-established therapeutic technique
      in neuropediatrics even in newborns or infants with vascular lesions in different
      parts of the body. Rhabdomyosarcoma is a malignant solid tumor arising from
      mesenchymal tissue that primarily affects children. We describe the procedure
      used to treat a large vascularized orbital rhabdomyosarcoma in a 38-day-old
      infant with application of partial tumor vascular bed embolization via external
      carotid end internal maxillary artery using PVA particles prior to gross
      excisional biopsy. We stress the significance of the preoperative embolization in
      infants with large highly vascularized tumor in order to reduce surgical blood
      loss and increase the probability of maximum lesion resection. 

PMID- 24300006
TI  - Neuroform stent applications in ruptured intracranial aneurysms with small parent
      vessels.
AB  - The Neuroform stent is a device specifically designed for use in cerebral vessels
      and is increasingly being used in the embolization of broad-necked aneurysms, but
      long-term results are unsatisfactory. Reconstructive treatments using stents
      improve the occlusion rate and protect parent vessels. Stent-assisted coiling of
      broad-necked cerebral aneurysms is a technique that has rendered most aneurysms
      amenable to coiling. Recently, the use of stent-assisted coiling with
      preservation of the parent vessel lumen has been described in some series.
      Several studies have shown that with the advances in device technology
      intracranial stenting is feasible even in the distal part of the ICA. But,
      endovascular treatment of these aneurysms (small parent vessel less than 2.0 mm)
      in Neuroform stent-assisted coiling has no clinical applications. These lesions
      have seemed more difficult to treat than other aneurysms because of subsequent
      thrombus formation and vessel trauma after stent deployment and navigation. The
      purpose of this study was to review the safety and durability of our aneurysms
      treated with stent-assisted coiling of ruptured aneurysms with small parent
      vessesl. 

PMID- 24300007
TI  - Angiographic exclusion of intracranial arteriovenous malformations using onyx(r).
AB  - Historically, endovascular treatment for cerebral arteriovenous malformations
      (AVMs) has been reserved as an adjunct to other modalities, namely radiosurgery
      and microsurgery, as the cure rate for cerebral AVMs treated solely with
      endovascular technique and older embolic agents is low. We report a series of
      five consecutive patients treated successfully with Onyx(r), the newest available
      embolic agent, with resultant angiographic cure. Five patients aged three, nine,
      33, 49, and 63 years were treated endovascularly for cerebral AVMs with a total
      of 19 embolizations with Onyx((r)). All procedures were performed under general
      anesthesia with biplanar fluoroscopy. Complete angiographic obliteration of the
      AVM nidus was obtained in all cases with no residual filling. No immediate
      hemorrhagic or thromboembolic complications were observed. This early experience
      suggests that Onyx(r) has excellent embolization potential, and endovascular cure
      of AVMs may now be achieved with single modality therapy. Long terms data needs
      to be collected to further validate this observation. 

PMID- 24300008
TI  - Transvenous embolization with onyx for cavernous sinus dural arteriovenous
      fistula. A report of two cases.
AB  - Previous treatments for cavernous dural arteriovenous fistulas (DAVF) include
      transarterial embolization with NBCA and transvenous embolization with platinum
      coils. This paper presents two cases of cavernous sinus dural arterial venous
      fistula successfully treated via a transvenous approach with Onyx. Case 1. A 54
      year-old man presented with blepharotosis, diplopia and chemosis. Cerebral
      angiography demonstrated a cavernous DAVF, which was successfully treated via
      inferior petrosal sinus with a combination of Onyx and platinum coils. Case 2. A
      36-year-old woman was admitted after incomplete transarterial embolization of a
      dural cavernous fistula. The patien's symptoms resolved almost completely after
      embolization with Onyx-34 via the superior ophthalmic vein. To our knowledge,
      only two such cases have been reported in the literature. The advantages of Onyx
      make it an attractive alternative to the various platinum coils already
      described. 

PMID- 24300009
TI  - Transarterial and transvenous embolization of a tentorial dural arteriovenous
      fistula. A case report.
AB  - Various treatments of tentorial dural arteriovenous fistulas have been assessed,
      but there are only two pertinent literature reports on percutaneous transvenous
      coil embolization. We describe the case of a patient with tentorial dural
      arteriovenous fistula coiled transvenously. 

PMID- 24300010
TI  - Trigeminocardiac reflex in transvenous packing of the cavernous sinus with onyx
      for dural arteriovenous fistula. A case report.
AB  - Paper Withdrawn Because Already Published in AJNR American Journal of
      Neuroradiology 28: 1769 - 70 - October 2007. 

PMID- 24300011
TI  - Phenotypic and functional properties of feline dedifferentiated fat cells and
      adipose-derived stem cells.
AB  - It has been reported that mature adipocyte-derived dedifferentiated fat (DFAT)
      cells show multilineage differentiation potential similar to that observed in
      mesenchymal stem cells. Since DFAT cells can be prepared from a small quantity of
      adipose tissue, they could facilitate cell-based therapies in small companion
      animals such as cats. The present study examined whether multipotent DFAT cells
      can be generated from feline adipose tissue, and the properties of DFAT cells
      were compared with those of adipose-derived stem cells (ASCs). DFAT cells and
      ASCs were prepared from the floating mature adipocyte fraction and the stromal
      vascular fraction, respectively, of collagenase-digested feline omental adipose
      tissue. Both cell types were evaluated for growth kinetics, colony-forming unit
      fibroblast (CFU-F) frequency, immunophenotypic properties, and multilineage
      differentiation potential. DFAT cells and ASCs could be generated from
      approximately 1g of adipose tissue and were grown and subcultured on laminin
      coated dishes. The frequency of CFU-Fs in DFAT cells (35.8%) was significantly
      higher than that in ASCs (20.8%) at passage 1 (P1). DFAT cells and ASCs displayed
      similar immunophenotypes (CD44(+), CD90(+), CD105(+), CD14(-), CD34(-) and CD45(
      )). Alpha-smooth muscle actin-positive cells were readily detected in ASCs
      (15.2+/-7.2%) but were rare in DFAT cells (2.2+/-3.2%) at P1. Both cell types
      exhibited adipogenic, osteogenic, chondrogenic, and smooth muscle cell
      differentiation potential in vitro. In conclusion, feline DFAT cells exhibited
      similar properties to ASCs but displayed higher CFU-F frequency and greater
      homogeneity. DFAT cells, like ASCs, may be an attractive source for cell-based
      therapies in cats.

PMID- 24300013
TI  - Red blood cell transfusions and the risk of allosensitization in patients
      awaiting primary kidney transplantation.
AB  - BACKGROUND: Most studies of HLA sensitization after red blood cell transfusion in
      transplant candidates were done before widespread use of leuko reduced blood and
      based on relatively insensitive, nonspecific antibody assays. We evaluated the
      effect of transfusion on the breadth and magnitude of HLA antibody formation
      using current, sensitive, HLA-specific immunoassays. METHODS: Serial HLA antibody
      data were merged with transfusion data from the US Renal Data System for 1324
      patients on the kidney transplant wait list (2004-2010). Two study groups were
      identified: a matched cohort consisting of 89 patients who received transfusion
      and 251 patients who did not receive transfusion and a crossover cohort
      consisting of 69 patients. Changes in antibody levels and calculated panel
      reactive antibody (CPRA) were compared using chi and Sign tests, respectively.
      Logistic regression was used to estimate the relative risk of antibody responses.
      RESULTS: Among the matched cohort, 20% of those who received transfusion compared
      to 3% of those who did not receive transfusion exhibited an antibody response
      (P=0.001), whereas in the crossover cohort, 19% exhibited a response in those who
      received transfusion compared to 1% of those who did not receive transfusion
      (P=0.0001). Moreover, 26.3% of those who received transfusion had increased CPRA
      compared to 5.8% of those who did not receive transfusion . These effects were
      greater in women and blacks compared to men and whites, respectively.
      Importantly, patients who received transfusion were at an increased risk of a
      potentially crossmatch positive response (odds ratio=9.6, 95% confidence
      interval=3.0-30.7). CONCLUSIONS: Sensitization from transfusion can occur in up
      to 20% of transplant candidates, resulting in higher antibody levels and CPRA
      values that adversely impact access to transplantation. These results support
      transfusion avoidance whenever possible.

PMID- 24300012
TI  - Therapeutic hypothermia in Italian Intensive Care Units after 2010 resuscitation
      guidelines: still a lot to do.
AB  - BACKGROUND: Therapeutic hypothermia (TH) is one of three interventions that have
      demonstrated to improve patients' neurological outcome after cardiac arrest. The
      aim of this study was to investigate the effect of the 2010 resuscitation
      guidelines on TH implementation in various Italian Intensive Care Units (ICU).
      METHODS: A structured questionnaire was submitted to Italian ICU. The
      questionnaire was addressed to determine the procedures of TH in each ICU or, on
      the contrary, the reason for not employing the therapy. RESULTS: We obtained
      complete information from 770 of 847 Italian ICU (91%). Out of 405 Units included
      in the analysis only 223 (55.1%) reported to use TH in comatose patients after
      return of spontaneous circulation. The trend of TH implementation shows a stable
      increase, particularly after 2006 but there is no evident acceleration after the
      strong indication of the 2010 guidelines. There was a rise of about 3.4 times in
      the number of Italian ICU using TH as compared to the 2007 survey (an increase of
      68% per year). One hundred and eighty-two (44.9%) units did not use TH mainly
      because of lack of equipment, economic issues or the conviction of the difficulty
      of execution. CONCLUSIONS: TH is still under-used in Italy (55.1%) even though
      the therapy is strongly recommended in the 2010 guidelines. However, the increase
      in the adoption of hypothermia has been significant in the past 5 years
      (68%/years) and the awareness of the efficacy is almost consolidated among
      intensivists, being logistic problems the leading cause for non-adoption.

PMID- 24300014
TI  - Bone marrow-derived macrophage production.
AB  - Macrophages are critical components of the innate and adaptive immune responses,
      and they are the first line of defense against foreign invaders because of their
      powerful microbicidal activities. Macrophages are widely distributed throughout
      the body and are present in the lymphoid organs, liver, lungs, gastrointestinal
      tract, central nervous system, bone, and skin. Because of their repartition, they
      participate in a wide range of physiological and pathological processes.
      Macrophages are highly versatile cells that are able to recognize
      microenvironmental alterations and to maintain tissue homeostasis. Numerous
      pathogens have evolved mechanisms to use macrophages as Trojan horses to survive,
      replicate in, and infect both humans and animals and to propagate throughout the
      body. The recent explosion of interest in evolutionary, genetic, and biochemical
      aspects of host-pathogen interactions has renewed scientific attention regarding
      macrophages. Here, we describe a procedure to isolate and cultivate macrophages
      from murine bone marrow that will provide large numbers of macrophages for
      studying host-pathogen interactions as well as other processes. 

PMID- 24300015
TI  - Diabetes in South-East Asia: an update.
AB  - According to the recent estimates by the International Diabetes Federation (IDF),
      South East-Asia (SEA) Region consisting of India, Sri Lanka, Bangladesh, Bhutan,
      Mauritius and Maldives, is home to more than 72 million adults with diabetes in
      2013 and is expected to exceed 123 million in 2035. Nearly 95% of people with
      diabetes have type 2 diabetes (T2DM). Although type 1 diabetes (T1DM) is
      relatively rare in these countries, its prevalence is also rising. Furthermore, a
      large number (24.3 million) of people also have impaired glucose tolerance (IGT).
      Several characteristic differences are seen in the clinical and immunological
      presentation of these people when compared with their European counterparts. A
      sharp increase in the prevalence of T2DM has been observed in the SEA Region,
      both in urban and rural areas, which is mostly associated with the lifestyle
      transitions towards urbanisation and industrialisation. Evidence suggests that a
      large portion of T2DM may be preventable by lifestyle modification. However,
      morbidity and early mortality occur as a result of inadequate healthcare
      facilities for early detection and initiation of therapy, as well as suboptimal
      management of diabetes and associated morbidities. This is largely preventable by
      primary prevention of diabetes and enhancing awareness about the disease among
      the public and the healthcare providers. There is an urgent need for concerted
      efforts by government and non-governmental sectors to implement national
      programmes aimed at prevention, management and surveillance of the disease. 

PMID- 24300016
TI  - The IDF Diabetes Atlas methodology for estimating global prevalence of
      hyperglycaemia in pregnancy.
AB  - INTRODUCTION: Hyperglycaemia is one of the most prevalent metabolic disorders
      occurring during pregnancy. Limited data are available on the global prevalence
      of hyperglycaemia in pregnancy. The International Diabetes Federation (IDF) has
      developed a methodology for generating estimates of the prevalence of
      hyperglycaemia in pregnancy, including hyperglycaemia first detected in pregnancy
      and live births to women with known diabetes, among women of childbearing age (20
      49 years). METHODS: A systematic review of the literature for studies reporting
      the prevalence of gestational diabetes was conducted. Studies were evaluated and
      scored to favour those that were representative of a large population, conducted
      recently, reported age-specific estimates, and case identification was based on
      blood test. Age-specific prevalence data from studies were entered to produce
      estimates for five-year age groups using logistic regression to smooth curves,
      with age as the independent variable. The derived age-specific prevalence was
      adjusted for differences in diagnostic criteria in the underlying data. Cases of
      hyperglycaemia in pregnancy were derived from age-specific estimates of fertility
      and age-specific population estimates. Country-specific estimates were generated
      for countries with available data. Regional and global estimates were generated
      based on aggregation and extrapolation for 219 countries and territories.
      Available fertility rates and diabetes prevalence estimates were used to estimate
      the proportion of hyperglycaemia in pregnancy that may be due to total diabetes
      in pregnancy - pregnancy in women with known diabetes and diabetes first detected
      in pregnancy. RESULTS: The literature review identified 199 studies that were
      eligible for characterisation and selection. After scoring and exclusion
      requirements, 46 studies were selected representing 34 countries. More than 50%
      of selected studies came from Europe and North America and Caribbean. The
      smallest number of identified studies came from sub-Saharan Africa. The majority
      of studies were for high-income countries, although low- and middle-income
      countries were also represented. CONCLUSION: Prevalence estimates of
      hyperglycaemia in pregnancy are sensitive to the data from which they are
      derived. The IDF methodology is a transparent, reproducible, and modifiable
      method for estimating the burden of hyperglycaemia in pregnancy. More data are
      needed, in particular from developing countries, to strengthen the methodology.

PMID- 24300017
TI  - Diabetes in the Middle-East and North Africa: an update.
AB  - In recent decades, the prevalence of diabetes has risen dramatically in many
      countries of the International Diabetes Federation's (IDF) Middle-East and North
      Africa (MENA) Region. This increase has been driven by a range of factors that
      include rapid economic development and urbanisation; changes in lifestyle that
      have led to reduced levels of physical activity, increased intake of refined
      carbohydrates, and a rise in obesity. These changes have resulted in the
      countries of MENA Region now having among the highest rates of diabetes
      prevalence in the world. The current prevalence of diabetes in adults in the
      Region is estimated to be around 9.2%. Of the 34 million people affected by
      diabetes, nearly 17 million were undiagnosed and therefore at considerable risk
      of diabetes complications and poor health outcomes. Enhanced research on the
      epidemiology of diabetes in the MENA Region needs to be combined with more
      effective primary prevention of diabetes; and early detection and improved
      management of patients with established diabetes, including an increased focus on
      self-management and management in primary care and community settings. 

PMID- 24300018
TI  - Global estimates of undiagnosed diabetes in adults.
AB  - AIMS: The prevalence of diabetes is rapidly increasing worldwide. Type 2 diabetes
      may remain undetected for many years, leading to severe complications and
      healthcare costs. This paper provides estimates of the prevalence of undiagnosed
      diabetes mellitus (UDM), using available data from high quality representative
      population-based sources. METHODS: Data sources reporting both diagnosed and
      previously undiagnosed diabetes were identified and selected according to
      previously described IDF methodology for diabetes in adults (aged 20-79).
      Countries were divided into 15 data regions based on their geographic IDF Region
      and World Bank income classification. The median UDM proportion was calculated
      from selected data sources for each of data region. The number of UDM cases in
      2013 was calculated from country, age and sex-specific estimates of known
      diabetes cases and data region-specific UDM proportion. RESULTS: Of 744 reviewed
      data sources, 88 sources representing 74 countries had sufficient information and
      were selected for generation of estimates of UDM. Globally, 45.8%, or 174.8
      million of all diabetes cases in adults are estimated to be undiagnosed, ranging
      from 24.1% to 75.1% across data regions. An estimated 83.8% of all cases of UDM
      are in low- and middle-income countries. At a country level, Pacific Island
      nations have the highest prevalence of UDM. CONCLUSIONS: There is a high
      proportion of UDM globally, and especially in developing countries. Further high
      quality studies of UDM are needed to strengthen future estimates.

PMID- 24300019
TI  - Diabetes in Europe: an update.
AB  - Diabetes is among the leading causes of death in the IDF Europe Region (EUR),
      continues to increase in prevalence with diabetic macro- and microvascular
      complications resulting in increased disability and enormous healthcare costs. In
      2013, the number of people with diabetes is estimated to be 56 million in EUR
      with an overall estimated prevalence of 8.5%. However, estimates of diabetes
      prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in
      Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between
      countries with stable prevalence since 2002 for many countries but a doubling of
      diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million
      people with diabetes is projected for the EUR. Prevalence of type 1 has also
      increased over the past 20 years in EUR and there was estimated to be 129,350
      cases in children aged 0-14 years in 2013. Registries provide valid information
      on incidence of type 1 diabetes with more complete data available for children
      than for adults. There are large differences in distribution of risk factors for
      diabetes at the population level in EUR. Modifiable risk factors such as obesity,
      physical inactivity, smoking behaviour (including secondhand smoking),
      environmental pollutants, psychosocial factors and socioeconomic deprivation
      could be tackled to reduce the incidence of type 2 diabetes in Europe. In
      addition, diabetes management is a major challenge to health services in the
      European countries. Improved networking practices of health professionals and
      other stakeholders in combination with empowerment of people with diabetes and
      continuous quality monitoring need to be further developed in Europe. 

PMID- 24300021
TI  - Middle-ear involvement in type I Gaucher's disease - a unique case.
AB  - OBJECTIVE: Gaucher's disease is a rare autosomal recessive lysosomal storage
      disease. We describe a unique case of middle-ear involvement presenting with
      hearing loss. CASE REPORT: A five-year-old boy with known Gaucher's disease
      presented with bilateral hearing impairment and conductive hearing loss on pure
      tone audiometry with flat tympanometry traces. INTERVENTION: Exploratory
      Tympanomastoidectomy revealed inflammatory material filling the mastoid and the
      middle ear. Histological analysis confirmed Gaucher cell infiltrates. CONCLUSION:
      This is the first detailed report in the english language literature of Gaucher's
      disease affecting the middle ear and the mastoid. We discuss the disease process
      and suggest future management options.

PMID- 24300020
TI  - Global estimates of the prevalence of hyperglycaemia in pregnancy.
AB  - AIMS: We estimated the number of live births worldwide and by IDF Region who
      developed hyperglycaemia in pregnancy in 2013, including total diabetes in
      pregnancy (known and previously undiagnosed diabetes) and gestational diabetes.
      METHODS: Studies reporting prevalence of hyperglycaemia first-detected in
      pregnancy (formerly termed gestational diabetes) were identified using PubMed and
      through a review of cited literature. A simple scoring system was developed to
      characterise studies on diagnostic criteria, year study was conducted, study
      design, and representation. The highest scoring studies by country with
      sufficient detail on methodology for characterisation and reporting at least
      three age-groups were selected for inclusion. Forty-seven studies from 34
      countries were used to calculate age-specific prevalence of hyperglycaemia first
      detected in pregnancy in women 20-49 years. Adjustments were then made to account
      for heterogeneity in screening method and blood glucose diagnostic threshold in
      studies and also to align with recently published diagnostic criteria as defined
      by the WHO for hyperglycaemia first detected in pregnancy. Prevalence rates were
      applied to fertility and population estimates to determine regional and global
      prevalence of hyperglycaemia in pregnancy for 2013. An estimate of the proportion
      of cases of hyperglycaemia in pregnancy due to total diabetes in pregnancy was
      calculated using age- and sex-specific estimates of diabetes from the IDF
      Diabetes Atlas and applied to age-specific fertility rates. RESULTS: The global
      prevalence of hyperglycaemia in pregnancy in women (20-49 years) is 16.9%, or
      21.4 million live births in 2013. An estimated 16.0% of those cases may be due to
      total diabetes in pregnancy. The highest prevalence was found in the South-East
      Asia Region at 25.0% compared with 10.4% in the North America and Caribbean
      Region. More than 90% of cases of hyperglycaemia in pregnancy are estimated to
      occur in low- and middle-income countries. CONCLUSION: These are the first global
      estimates of hyperglycaemia in pregnancy and conform to the new WHO
      recommendations regarding diagnosis and also include estimates of live births in
      women with known diabetes. They indicate the importance of the disease from a
      public health and maternal and child health perspective, particularly in
      developing countries.

PMID- 24300022
TI  - Therapeutic angiogenesis improves fibrinolytic imbalance in patients with
      critical limb ischemia.
AB  - The mechanisms of fibrinolysis have been suggested to be linked to the
      pathogenesis of peripheral artery disease. The impact of therapeutic angiogenesis
      on the parameters of fibrinolysis was studied in critical limb ischemia (CLI).
      CLI patients (N = 29) and blood donors as controls (N = 29) were enrolled. Bone
      marrow (600 +/- 50 ml) was centrifuged (3200g, 20 min, 22 degrees C), bone marrow
      derived mononuclear cells (100-120 ml) were separated by Optipress I and
      implanted into the ischemic limb using intramuscular injections. ELISA was
      employed for the assessment of plasma tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor-1 (PAI-1) levels. Patients were followed-up prior
      to the procedure and after 1, 3 and 6 months. All stage-IV patients (N = 22) had
      ischemic lesions. The lesions resolved in 10 patients. Five patients underwent
      major amputation; they all were stage-IV. Ischemic lesions persisted in seven
      patients beyond 6 months. The t-PA levels were higher in patients compared with
      the healthy controls both at baseline (P < 0.01) and after 6 months (P < 0.05).
      No significant changes were observed in the t-PA levels during the follow-up. PAI
      1 was higher in patients than in the healthy individuals at baseline (P < 0.001)
      and at month 1 (P < 0.05). However, no difference in PAI-1 levels between the
      patients and the healthy individuals was found after 3 and 6 months. The PAI-1
      levels were significantly downregulated during the follow-up compared with the
      baseline (P < 0.0001). Therapeutic angiogenesis for the CLI downregulates PAI-1
      levels, thus having a systemic effect on fibrinolysis. 

PMID- 24300023
TI  - An unusual presentation of heparin-induced thrombocytopenia in the setting of
      catheter-directed ablation of atrial fibrillation.
AB  - Heparin-induced thrombocytopenia type 2 is an immune-mediated phenomenon
      associated with heparin exposure that has the potential to evolve into life
      threatening thrombosis if not recognized and treated early. Lack of immediate
      availability of a confirmatory assay often leaves the diagnosis to the
      clinician's discretion. Despite a high negative predictive value, the clinical
      '4Ts' scoring system carries a small but a real risk of missing the diagnosis,
      especially with atypical presentations. We describe one such case of rapid-onset,
      heparin-induced thrombocytopenia with thrombosis that developed in the setting of
      catheter-directed ablation of atrial fibrillation, several months after a brief
      exposure to low-molecular-weight heparin. The clinical scenario as well as the
      risk of progressing to catastrophic complications prompted immediate
      discontinuation of all heparin products and treatment with a direct thrombin
      inhibitor, despite a low pretest clinical score. 

PMID- 24300024
TI  - Using coculture to detect chemically mediated interspecies interactions.
AB  - In nature, bacteria rarely exist in isolation; they are instead surrounded by a
      diverse array of other microorganisms that alter the local environment by
      secreting metabolites. These metabolites have the potential to modulate the
      physiology and differentiation of their microbial neighbors and are likely
      important factors in the establishment and maintenance of complex microbial
      communities. We have developed a fluorescence-based coculture screen to identify
      such chemically mediated microbial interactions. The screen involves combining a
      fluorescent transcriptional reporter strain with environmental microbes on solid
      media and allowing the colonies to grow in coculture. The fluorescent
      transcriptional reporter is designed so that the chosen bacterial strain
      fluoresces when it is expressing a particular phenotype of interest (i.e. biofilm
      formation, sporulation, virulence factor production, etc.) Screening is performed
      under growth conditions where this phenotype is not expressed (and therefore the
      reporter strain is typically nonfluorescent). When an environmental microbe
      secretes a metabolite that activates this phenotype, it diffuses through the agar
      and activates the fluorescent reporter construct. This allows the inducing
      metabolite-producing microbe to be detected: they are the nonfluorescent colonies
      most proximal to the fluorescent colonies. Thus, this screen allows the
      identification of environmental microbes that produce diffusible metabolites that
      activate a particular physiological response in a reporter strain. This
      publication discusses how to: a) select appropriate coculture screening
      conditions, b) prepare the reporter and environmental microbes for screening, c)
      perform the coculture screen, d) isolate putative inducing organisms, and e)
      confirm their activity in a secondary screen. We developed this method to screen
      for soil organisms that activate biofilm matrix-production in Bacillus subtilis;
      however, we also discuss considerations for applying this approach to other
      genetically tractable bacteria. 

PMID- 24300025
TI  - Estimation of physical functional disabilities and long-term care needs for
      patients under maintenance hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Physical functional disabilities in hemodialysis (HD)
      patients may increase their mortality and long-term care needs. The aim of this
      study was to estimate the changes of proportion for different physical functional
      disabilities along time after beginning HD and the lifelong care needs. METHODS:
      We used a population-based cohort consisting of 84,657 incident HD patients in
      Taiwan between 1998 and 2009 to estimate the survival function and extrapolate to
      lifetime through a semiparametric method. The Barthel Index (BI) was used to
      measure the functional disability levels cross-sectionally in 1334 HD patients
      recruited from 9 HD centers. A BI score <50 was considered as severe disability.
      Lifetime care needs were obtained by extrapolating the age-stratified survival
      functions to lifetime and then multiplying them with proportions of different
      kinds of functional disabilities over time. RESULTS: On average, HD patients had
      at least 6.4, 2.0, and 1.3 years without disability, with moderate disability,
      and severe disability, respectively. The most common care needs were stair
      climbing and bathing, which were 3.0 and 1.7 years, respectively. HD patients
      were expected to have about 3 years living with disabilities for those beginning
      HD at an age above 35 years; however, the older the patient, the higher the
      proportion of functional disabilities and care needs. CONCLUSIONS: HD patients
      are in need of long-term care and require early intervention and resource
      planning. The method developed in this study can also be applied to other chronic
      illnesses with various functional disabilities.

PMID- 24300026
TI  - Optical detection of E. coli bacteria by mesoporous silicon biosensors.
AB  - A label-free optical biosensor based on a nanostructured porous Si is designed
      for rapid capture and detection of Escherichia coli K12 bacteria, as a model
      microorganism. The biosensor relies on direct binding of the target bacteria
      cells onto its surface, while no pretreatment (e.g. by cell lysis) of the studied
      sample is required. A mesoporous Si thin film is used as the optical transducer
      element of the biosensor. Under white light illumination, the porous layer
      displays well-resolved Fabry-Perot fringe patterns in its reflectivity spectrum.
      Applying a fast Fourier transform (FFT) to reflectivity data results in a single
      peak. Changes in the intensity of the FFT peak are monitored. Thus, target
      bacteria capture onto the biosensor surface, through antibody-antigen
      interactions, induces measurable changes in the intensity of the FFT peaks,
      allowing for a 'real time' observation of bacteria attachment. The mesoporous Si
      film, fabricated by an electrochemical anodization process, is conjugated with
      monoclonal antibodies, specific to the target bacteria. The immobilization,
      immunoactivity and specificity of the antibodies are confirmed by fluorescent
      labeling experiments. Once the biosensor is exposed to the target bacteria, the
      cells are directly captured onto the antibody-modified porous Si surface. These
      specific capturing events result in intensity changes in the thin-film optical
      interference spectrum of the biosensor. We demonstrate that these biosensors can
      detect relatively low bacteria concentrations (detection limit of 10(4) cells/ml)
      in less than an hour. 

PMID- 24300028
TI  - Epilepsy prevalence, potential causes and social beliefs in Ebonyi State and
      Benue State, Nigeria.
AB  - Epilepsy is a common neurological disorder in Nigeria. Many individuals are
      affected in rural areas, although prevalence data is not available. In this study
      we aimed to establish the prevalence of epilepsy in a rural community in south
      east Nigeria, a community suspected for having a high number of people living
      with epilepsy. We compared this with the prevalence in a nearby semi-urban
      community in north-central Nigeria. In both communities we identified potential
      causes of epilepsy and obtained information on the social beliefs regarding
      epilepsy. We used door-to-door surveys and focus group discussions. The epilepsy
      prevalence in the rural community was 20.8/1000 [95% confidence interval (CI):
      15.7-27.4]. The prevalence in the semi-rural community was lower, namely 4.7/1000
      [CI: 3.2-6.9]. The difference in prevalence was highly significant (chi(2)-test,
      p<0.0001). In both communities most people with epilepsy were in the age range of
      7-24 years. Causes that might be contributory to the prevalence of epilepsy in
      both communities included poor obstetric practices, frequent febrile convulsions,
      head trauma, meningitis and neurocysticercosis. In both communities we found
      stigma of people with epilepsy. In conclusion, the epilepsy prevalence in the
      semi-urban community is similar to that in industrialized countries. In contrast,
      the rural community has a much higher prevalence. This may require the
      establishment of specific community-based epilepsy control programs. Community
      interventions should focus on treatment of acute epilepsy and on stigma
      reduction. 

PMID- 24300027
TI  - Cathepsin S inhibition suppresses systemic lupus erythematosus and lupus
      nephritis because cathepsin S is essential for MHC class II-mediated CD4 T cell
      and B cell priming.
AB  - OBJECTIVES: Major histocompatibility complex (MHC) class II-mediated priming of T
      and B lymphocytes is a central element of autoimmunity in systemic lupus
      erythematosus (SLE) and lupus nephritis. The cysteine protease cathepsin S
      degrades the invariant peptide chain during MHC II assembly with antigenic
      peptide in antigen-presenting cells; therefore, we hypothesised that cathepsin S
      inhibition would be therapeutic in SLE. METHODS: We developed a highly specific
      small molecule, orally available, cathepsin S antagonist, RO5461111, with
      suitable pharmacodynamic and pharmacokinetic properties that efficiently
      suppressed antigen-specific T cell and B cell priming in vitro and in vivo.
      RESULTS: When given to MRL-Fas(lpr) mice with SLE and lupus nephritis, RO5461111
      significantly reduced the activation of spleen dendritic cells and the subsequent
      expansion and activation of CD4 T cells and CD4/CD8 double-negative T cells.
      Cathepsin S inhibition impaired the spatial organisation of germinal centres,
      suppressed follicular B cell maturation to plasma cells and Ig class switch. This
      reversed hypergammaglobulinemia and significantly suppressed the plasma levels of
      numerous IgG (but not IgM) autoantibodies below baseline, including anti-dsDNA.
      This effect was associated with less glomerular IgG deposits, which protected
      kidneys from lupus nephritis. CONCLUSIONS: Together, cathepsin S promotes SLE by
      driving MHC class II-mediated T and B cell priming, germinal centre formation and
      B cell maturation towards plasma cells. These afferent immune pathways can be
      specifically reversed with the cathepsin S antagonist RO5461111, which prevents
      lupus nephritis progression even when given after disease onset. This novel
      therapeutic strategy could correct a common pathomechanism of SLE and other
      immune complex-related autoimmune diseases.

PMID- 24300030
TI  - Overadjustment in regression analyses: considerations when evaluating
      relationships between body mass index, muscle strength, and body size.

PMID- 24300029
TI  - Significance of MDR1 gene polymorphism C3435T in predicting drug response in
      epilepsy.
AB  - Antiepileptic drug (AED) treatment in epilepsy is often compromised by the
      unpredictability of efficacy and inter-individual variability among patients,
      which at least in part is the result of genetic variation. The idea to determine
      an individual's response to a prescribed medicine came into inception around 29
      years ago. Pharmacogenetics is used to predict the drug response and efficacy, as
      well as potential adverse effects. We investigated the functional significance of
      the C3435T polymorphism of the MDR1 gene in a South Indian population. The
      patients were divided into responders and non-responders based on their clinical
      outcome and AED response. The risk of drug resistance was significantly higher in
      patients bearing TT genotype in comparison to carriers of the homozygous CC
      genotype [TT vs. CC, chi(2)=12.52; p=0.001, Odds ratio=2.34 (95% CI: 1.942
      11.32)]. We suggest that the influence of the C3435T polymorphism in predicting
      the drug-resistance in epilepsy, might be significant and further investigations
      focusing on carbamazepine and phenytoin, in various ethnic populations are
      necessary to clarify the effect of C3435T polymorphism on the multidrug
      resistance in epilepsy patients. 

PMID- 24300031
TI  - Growth hormone replacement therapy prevents sarcopenia by a dual mechanism:
      improvement of protein balance and of antioxidant defenses.
AB  - The aim of our study was to elucidate the role of growth hormone (GH) replacement
      therapy in three of the main mechanisms involved in sarcopenia: alterations in
      mitochondrial biogenesis, increase in oxidative stress, and alterations in
      protein balance. We used young and old Wistar rats that received either placebo
      or low doses of GH to reach normal insulin-like growth factor-1 values observed
      in the young group. We found an increase in lean body mass and plasma and hepatic
      insulin-like growth factor-1 levels in the old animals treated with GH. We also
      found a lowering of age-associated oxidative damage and an induction of
      antioxidant enzymes in the skeletal muscle of the treated animals. GH replacement
      therapy resulted in an increase in the skeletal muscle protein synthesis and
      mitochondrial biogenesis pathways. This was paralleled by a lowering of
      inhibitory factors in skeletal muscle regeneration and in protein degradation. GH
      replacement therapy prevents sarcopenia by acting as a double-edged sword,
      antioxidant and hypertrophic. 

PMID- 24300033
TI  - Persistent sodium current properties in hippocampal CA1 pyramidal neurons of
      young and adult rats.
AB  - Persistent tetrodotoxin-sensitive sodium current (INaP) plays an important role
      in cellular and neuronal network excitability in physiological conditions and
      under different pathological circumstances. However, developmental changes in
      INaP properties remain largely unclear. In the present study using whole cell
      patch clamp technique we evaluated INaP properties in CA1 hippocampal pyramidal
      neurons isolated from young (postnatal day (P) 12-16) and adult (P60-75) rats. We
      show that the INaP density is substantially larger in the adult group. Although
      INaP inactivation characteristics were found to be similar in both groups,
      voltage dependence of INaP activation is shifted to more negative membrane
      potentials (young: -48.6+/-0.5mV vs. adult: -52.4+/-0.2mV, p<0.01). Our data
      indicates the increase of INaP contribution in the basal membrane sodium
      conductivity in the mature hippocampus. 

PMID- 24300038
TI  - Modeling the tumor extracellular matrix: Tissue engineering tools repurposed
      towards new frontiers in cancer biology.
AB  - Cancer progression is mediated by complex epigenetic, protein and structural
      influences. Critical among them are the biochemical, mechanical and architectural
      properties of the extracellular matrix (ECM). In recognition of the ECM's
      important role, cancer biologists have repurposed matrix mimetic culture systems
      first widely used by tissue engineers as new tools for in vitro study of tumor
      models. In this review we discuss the pathological changes in tumor ECM, the
      limitations of 2D culture on both traditional and polyacrylamide hydrogel
      surfaces in modeling these characteristics and advances in both naturally derived
      and synthetic scaffolds to facilitate more complex and controllable 3D cancer
      cell culture. Studies using naturally derived matrix materials like Matrigel and
      collagen have produced significant findings related to tumor morphogenesis and
      matrix invasion in a 3D environment and the mechanotransductive signaling that
      mediates key tumor-matrix interaction. However, lack of precise experimental
      control over important matrix factors in these matrices have increasingly led
      investigators to synthetic and semi-synthetic scaffolds that offer the
      engineering of specific ECM cues and the potential for more advanced experimental
      manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for
      example, facilitate highly biocompatible 3D culture, modular bioactive features
      like cell-mediated matrix degradation and complete independent control over
      matrix bioactivity and mechanics. Future work in PEG or similar reductionist
      synthetic matrix systems should enable the study of increasingly complex and
      dynamic tumor-ECM relationships in the hopes that accurate modeling of these
      relationships may reveal new cancer therapeutics targeting tumor progression and
      metastasis. 

PMID- 24300032
TI  - The tail that wags the dog: p12, the smallest subunit of DNA polymerase delta, is
      degraded by ubiquitin ligases in response to DNA damage and during cell cycle
      progression.
AB  - DNA polymerase delta (Pol delta) is a key enzyme in eukaryotic DNA replication.
      Human Pol delta is a heterotetramer whose p12 subunit is degraded in response to
      DNA damage, leading to the in vivo conversion of Pol delta4 to Pol delta3. Two E3
      ubiquitin ligases, RNF8 and CRL4(Cdt2), participate in the DNA damage-induced
      degradation of p12. We discuss how these E3 ligases integrate the formation of
      Pol delta3 and ubiquitinated PCNA for DNA repair processes. CRL4(Cdt2) partially
      degrades p12 during normal cell cycle progression, thereby generating Pol delta3
      during S phase. This novel finding extends the current view of the role of Pol
      delta3 in DNA repair and leads to the hypothesis that it participates in DNA
      replication. The coordinated regulation of licensing factors and Pol delta3 by
      CRL4(Cdt2) now opens new avenues for control of DNA replication. A parallel study
      of Pol delta4 and Pol delta3 in Okazaki fragment processing provides evidence for
      a role of Pol delta3 in DNA replication. We discuss several new perspectives of
      the role of the 2 forms of Pol delta in DNA replication and repair, as well the
      significance of the integration of p12 regulation in DNA repair and cell cycle
      progression. 

PMID- 24300039
TI  - In praise of birth cohorts: norovirus infection, disease, and immunity.

PMID- 24300040
TI  - Invasive pneumococcal disease, comorbidities, and polysaccharide vaccine use in
      children aged 5-15 years in England and Wales.
AB  - BACKGROUND: In the United Kingdom, the 23-valent pneumococcal polysaccharide
      vaccine (PPV23) is recommended in addition to routine pneumococcal conjugate
      vaccination for at-risk children aged >=2 years. This study describes the
      epidemiology, serotype distribution, clinical characteristics, vaccination
      status, and reasons for nonvaccination in children aged 5-15 years with invasive
      pneumococcal disease (IPD). METHODS: Public Health England conducts enhanced
      national surveillance of IPD in England and Wales. In 2012, general practitioners
      (GPs) were contacted to complete a questionnaire for children aged 5-15 years
      with laboratory-confirmed IPD diagnosed during 2 epidemiological years, July 2009
      June 2011. RESULTS: During 2009-2011, 447 IPD episodes occurred in 439 children
      (incidence, 2.2/100 000), and GPs of 423 of the 439 (96.4%) children completed
      the questionnaire. Comorbidity was reported in 124 (29.3%); a third each were
      immunocompromised or had chronic respiratory disease or other comorbidities.
      Pneumonia was the most common presentation (332/439 [75.6%]), and IPD-related
      case fatality was 1.8% (8/439). Only 26.6% (33/124) of children with
      comorbidities had received PPV23, and development of PPV23-type IPD was not
      associated with prior PPV23 vaccination (adjusted odds ratio [AOR], 1.09; 95%
      confidence interval [CI], .36-3.32; P = .88), even when analysis was restricted
      to the extra 11 PPV23 serotypes not contained in the 13-valent pneumococcal
      conjugate vaccine (AOR, 1.70; 95% CI, .30-9.76; P = .55). GPs of eligible but
      unvaccinated cases with comorbidities were mostly unaware that the child required
      PPV23 and/or expected pediatricians to inform them to administer the vaccine.
      CONCLUSIONS: Only a quarter of children with comorbidities who developed IPD had
      received PPV23 prior to infection. Among PPV23-vaccinated children with
      comorbidities, however, there was no evidence of protection against PPV23
      serotypes.

PMID- 24300041
TI  - An economic analysis: is fidaxomicin worth the cost?

PMID- 24300043
TI  - Cost-effectiveness of fidaxomicin for Clostridium difficile treatment.

PMID- 24300042
TI  - Multiple norovirus infections in a birth cohort in a Peruvian Periurban
      community.
AB  - BACKGROUND: Human noroviruses are among the most common enteropathogens globally,
      and are a leading cause of infant diarrhea in developing countries. However, data
      measuring the impact of norovirus at the community level are sparse. METHODS: We
      followed a birth cohort of children to estimate norovirus infection and diarrhea
      incidence in a Peruvian community. Stool samples from diarrheal episodes and
      randomly selected nondiarrheal samples were tested by polymerase chain reaction
      for norovirus genogroup and genotype. Excretion duration and rotavirus
      coinfection were evaluated in a subset of episodes. RESULTS: Two hundred twenty
      and 189 children were followed to 1 and 2 years of age, respectively. By 1 year,
      80% (95% confidence interval [CI], 75%-85%) experienced at least 1 norovirus
      infection and by 2 years, 71% (95% CI, 65%-77%) had at least 1 episode of
      norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more
      frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII
      genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs
      8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup
      were common, but repeat infections by the same genotype were rare. Mean length
      for-age z score at 12 months was lower among children with prior norovirus
      infection compared to uninfected children (coefficient: -0.33 [95% CI, -.65 to 
      .01]; P = .04); the effect persisted at 24 months. CONCLUSIONS: Norovirus
      infection occurs early in life and children experience serial infections with
      multiple genotypes, suggesting genotype-specific immunity. An effective vaccine
      would have a substantial impact on morbidity, but may need to target multiple
      genotypes.

PMID- 24300044
TI  - Reply to Simon, Shah et al, and Hartzema and Chen.

PMID- 24300045
TI  - The challenge of preventing invasive pneumococcal disease in children with
      comorbid illnesses.

PMID- 24300046
TI  - Is fidaxomicin worth the cost? The verdict is still out!

PMID- 24300047
TI  - The crosstalk between plant microRNA biogenesis factors and the spliceosome.
AB  - Many of the plant microRNA (miRNA) genes contain introns. The miRNA-containing
      hairpin loop structure is predominantly located within the first exon of such pri
      miRNAs. We have shown that the downstream intron and its splicing are important
      for the regulation of the processing of these pri-miRNAs. The 5' splice site in
      MIR genes is essential in the process of miRNA biogenesis. We postulate that the
      presence of yet undefined interactions between U1 snRNP and the pri-miRNA
      processing machinery leads to an increase in the efficiency of miRNA biogenesis.
      The 5' splice site also decreases the accessibility of the polyadenylation
      machinery to the pri-miRNA polyA signal located within the same intron. It is
      likely that the spliceosome assembly controls the length and structure of MIR
      primary transcripts, and regulates mature miRNA levels. The emerging picture
      shows that introns, splicing, and/or alternative splicing have highly relevant
      roles in regulating the miRNA levels in very specific conditions that contribute
      to proper plant response to stress conditions. 

PMID- 24300048
TI  - A 5-year follow-up of deep brain stimulation in Huntington's disease.

PMID- 24300049
TI  - Swallowing improvement after levodopa treatment in idiopathic Parkinson's
      disease: lack of evidence. Authors' reply.

PMID- 24300050
TI  - Individual and institutional push and pull factors as predictors of retirement
      timing in Europe: A multilevel analysis.
AB  - The number of retired people in Europe has increased significantly in recent
      decades. It remains unclear, however, whether individuals are more likely to be
      pulled toward retirement by their expectations about life after retirement than
      they are to be pushed out of the labour market due to poor health or dislike of
      one's job. The fact that retirement timing differs rather considerably between
      European countries suggests that not only micro, but also macro push (i.e. labour
      market constraints) and pull (i.e. economic incentives) factors influence
      retirement decisions. This duality heightens the need to determine the influence
      of micro-level and macro-level push and pull indicators on the retirement timing
      of older workers (50+) in Europe. Results are obtained performing multilevel
      event history analysis using longitudinal micro data from the first (2004/05) and
      second (2006/07) waves of the Survey of Health, Ageing and Retirement in Europe
      and macro data derived from the Organisation for Economic Cooperation and
      Development (OECD) and Eurostat. The results indicate that at the individual
      level, older workers are pushed out due to health problems as well as being
      attracted towards retirement to spend time with their grandchildren. At the
      institutional level, financial incentives such as a high implicit tax on
      continued work and high expenditures on early exit schemes make retirement
      attractive, whereas the institutional push context is of lesser importance.

PMID- 24300051
TI  - Grandparenting across borders: American grandparents and their Israeli
      grandchildren in a transnational reality.
AB  - Families are increasingly dispersed across national borders. Americans in Israel
      are one migrant group that represents the worldwide phenomenon of
      transnationalism. Grandparents separated geographically from their grandchildren
      develop new means of communication with them and new kinds of relationships. This
      study uses ethnographic interviews with the grandparents of transnational,
      American-Israeli children and youth to offer an in-depth examination of the
      experience of grandparenting across borders. We find that grandparenting children
      who are both geographically distant and raised in a foreign culture necessitates
      the development of new ways of maintaining relationships with grandchildren. This
      study considers the impact of transnational migration on the extended family, on
      those left behind, who struggle with redefining their roles as grandparents and
      with the sense of being deprived of the roles they had expected to play.

PMID- 24300052
TI  - Coming together and pulling apart: Exploring the influence of functional status
      on co-resident relationships in assisted living.
AB  - Social relationships can have considerable influence on physical and mental well
      being in later life, particularly for those in long-term care settings such as
      assisted living (AL). Research set in AL suggests that other residents are among
      the most available social contacts and that co-resident relationships can affect
      life satisfaction, quality of life, and well-being. Functional status is a major
      factor influencing relationships, yet AL research has not studied in-depth or
      systematically considered the role it plays in residents' relationships. This
      study examines the influences of physical and mental function on co-resident
      relationships in AL and identifies the factors shaping the influence of
      functional status. We present an analysis of qualitative data collected over a
      one-year period in two distinct AL settings. Data collection included:
      participant observation, informal interviews, and formal in-depth interviews with
      staff, residents, administrators and visitors, as well as surveys with residents.
      Grounded theory methods guided our data collection and analysis. Our analysis
      identified the core category, "coming together and pulling apart", which
      signifies that functional status is multi-directional, fluid, and operates in
      different ways in various situations and across time. Key facility- (e.g.,
      admission and retention practices, staff intervention) and resident-level (e.g.,
      personal and situational characteristics) factors shape the influence of
      functional status on co-resident relationships. Based on our findings, we suggest
      strategies for promoting positive relationships among residents in AL, including
      the need to educate staff, families, and residents.

PMID- 24300053
TI  - Purpose and pleasure in late life: Conceptualising older women's participation in
      art and craft activities.
AB  - The fourth age, as the last stage of life, represents a final challenge to find
      personal meaning in the face of changing capacities, illness and disability.
      Participation in valued activities is important for sustaining interest in life
      and has been associated with enhanced health and well-being. Art and craft
      activities are a popular form of participation amongst women in late life with
      growing international interest in the potential for these types of activities to
      maintain health and well-being and address problems of social isolation. Drawing
      on open text comments from 114 women enrolled in the Australian Longitudinal
      Study on Women's Health and in-depth interviews with 23 women all aged in their
      eighties, this paper explores the nature of older women's participation in art
      and craft activities and conceptualises links between participation in these
      activities and health and well-being in late life. Participation in art and craft
      activities is complex and dynamic, comprising cognitive and physical processes
      infused with emotion and occurs in the context of social relationships, physical
      spaces, physical ailments and beliefs about the value of the activities. By
      participating in art and craft activities, older women find purpose in their
      lives, contributing to their subjective well-being whilst helping and being
      appreciated by others. They develop a self view as enabled and as such take on
      new art and craft challenges, continue to learn and develop as art and craft
      makers and remain open to new possibilities.

PMID- 24300054
TI  - 'We are not as alike, as you think' sense of individuality within the co-twin
      relationship along the life course.
AB  - We have explored how older twins experience and describe themselves in relation
      to their co-twin. The life stories of 20 older twins were analyzed with narrative
      analysis. Results showed that the twins described themselves from the point of
      differences in relation to the co-twin. This was based on experiences of how
      other people viewed them as alike, as well as on life events along the life
      course, which contributed to the perception of oneself as an individual in
      relation to the co-twin. The emphasis on unlikeness was therefore interpreted as
      a way of trying to establish a position as an individual within the co-twin
      relationship and to assert ones individuality to the rest of the social
      environment. To claim oneself as an individual was an ongoing identity work along
      the life course.

PMID- 24300055
TI  - Family, welfare state generosity and the vulnerability of older adults: A cross
      national study.
AB  - The availability of family can be considered a protective factor for aging well.
      In this article, we examine to what extent the family situation of older people
      creates vulnerability with respect to their quality of life. Because not everyone
      is vulnerable to the same degree, we try to identify the conditions under which
      older people benefit more from having family resources. Based on the resources
      perspective, we argue that the impact of family resources on life satisfaction is
      stronger for older people with fewer resources at both the individual level
      (material, physical and non-familial social resources) and the country level
      (welfare state services targeted at older adults). To test our hypotheses we make
      use of the fourth wave of the European Values Study, and the MULTILINKS Social
      Policy Indicators database. In general our data offer support for the idea that
      the presence of intimate family ties (with partner and children) can be
      considered an important resource for achieving psychological well-being, whereas
      their absence or loss may act as a constraint. Our vulnerability argument is
      partly supported by the findings. Partner resources are more important for the
      life satisfaction of older people with a low education and health problems.
      Similarly, having children only improves the life-satisfaction of lower educated
      older adults. However, family resources are not more important for older people
      with fewer material resources or for older people living in countries with low
      services levels targeted at older adults.

PMID- 24300056
TI  - Pioneering partnerships: Resident involvement from multiple perspectives.
AB  - Resident involvement in residential care homes is a challenge due to shortcomings
      of consumerist and formal approaches such as resident councils. The PARTNER
      approach aims to involve residents through collective action to improve their
      community life and wellbeing. The purpose of this article is to provide insights
      into the process of resident involvement by the PARTNER approach from the
      perspectives of multiple stakeholders, including residents, volunteers and staff
      members. A responsive evaluation was conducted, using participant observations,
      semi-structured interviews with residents, volunteers and professionals (n=16),
      and three focus groups. The findings show that critical elements in this process
      of resident involvement were the agenda-setting by residents, the formation of a
      cohesive resident group, the sharing of experiences and stories, the development
      of collective action, and the development of partnerships between residents and
      professionals and other stakeholder groups. Residents developed actions (gallery
      parties and a buddy project) to strengthen social interactions and realized these
      with the help of volunteers and professionals. We conclude that bringing
      residents together around a shared topic creates room for activism and leads to
      empowerment, feelings of social belonging and learning processes. We argue that
      it is a worthwhile enterprise to further develop structural partnership relations
      between residents, volunteers and staff in residential care homes.

PMID- 24300057
TI  - The fourth age and the concept of a 'social imaginary': A theoretical excursus.
AB  - This paper explores the idea of the 'fourth age' as a form of social imaginary.
      During the latter half of the twentieth century and beyond, the cultural framing
      of old age and its modern institutionalisation within society began to lose some
      of its former chronological coherence. The 'pre-modern' distinction made between
      the status of 'the elder' and the state of 'senility' has re-emerged in the 'late
      modern' distinction between the 'third' and the 'fourth' age. The centuries-old
      distaste for and fear of old age as 'senility' has been compounded by the growing
      medicalization of later life, the emergence and expansion of competing narratives
      associated with the third age, and the progressive 'densification' of the
      disabilities within the older institutionalised population. The result can be
      seen as the emergence of a 'late modern' social imaginary deemed as the fourth
      age. This paper outlines the theoretical evolution of the concept of a social
      imaginary and demonstrates its relevance to aging studies and its applicability
      to the fourth age.

PMID- 24300058
TI  - The experiences of grandparents who have limited or no contact with their
      grandchildren.
AB  - PURPOSE OF THE STUDY: The matrilineal advantage theory suggests that paternal
      grandparents are more at risk of having little or no contact with their
      grandchildren. However, there is significant family diversity within Australia
      and we wished to understand the experiences of a wide range of grandparents in
      order to determine if the matrilineal theory can be effectively used in practice
      to identify those grandparents most at risk for estrangement. DESIGN AND METHODS:
      A convenience group of grandparents with little or no contact with grandchildren
      (n=38) told their stories in their own words using narratives obtained through
      interview or writing. RESULTS AND IMPLICATIONS: We found that paternal
      grandparents, as per the matrilineal advantage theory, were more likely to be
      estranged from their grandchildren when their son divorced, particularly when he
      was not the resident parent or when he re-partnered. However, in contrast, we
      found that maternal grandparents who experienced conflict in their relationship
      with their daughter were also at risk for estrangement. This occurred even when
      grandparents had previously been highly involved in the lives of their
      grandchildren. Some estrangements appeared to result from a cultural bias towards
      the nuclear family form. We argue that practitioners need not only to expand
      their understanding of the risk categories for estrangement, they also need to
      actively support parents and grandparents in creating and maintaining wider
      family support networks in order to improve family resilience.

PMID- 24300059
TI  - 'The engine just started coughing!' - Limits of physical performance, aging and
      career continuity in elite endurance sports.
AB  - This research examines male endurance athletes' experience of aging and/or
      reaching the perceived limits of physical performance. More specifically, the
      current study aimed to explore how existential meanings attached to these
      experiences are connected with athletes' decision-making concerning career
      continuity and retirement. Life story interviews were conducted with 10 Finnish
      runners and/or orienteers aged between 25 and 62 and the data was analyzed with
      an existential-narrative framework. Four major storylines related to aging were
      identified: The end of an era, putting things in perspective, the attitude has to
      change and winning was never the only motive. Our results suggest that endurance
      athletes possess diverse ways of bringing meaning to the experience of aging,
      both confirming and resisting the dominant cultural narrative of decline. While
      three athletes' stories confirmed the normativity of retirement when unable to
      improve their results anymore, other athletes demonstrated career continuity and
      positive aspects in the late career years, such as lack of competitive anxiety,
      finding perspective and increased enjoyment in running. We suggest that through
      awareness of alternative narratives, sport psychology consultants may be able to
      help their clients to explore new meanings in the potentially challenging and
      beneficial experiences of aging and athletic retirement.

PMID- 24300060
TI  - The secrets of highly active older adults.
AB  - Although physical activity is a recognized component in the management of many
      chronic diseases associated with aging, activity levels tend to progressively
      decline with increasing age (Manini & Pahor, 2009; Schutzer & Graves, 2004). In
      this article we examine the key factors that facilitate physical activity in
      highly active community-dwelling older adults. Using a strengths based approach,
      we examined the factors that facilitated physical activity in our sample of
      highly active older adults. Twenty-seven older adults participated in face-to
      face interviews. We extracted a sub-sample of 10 highly active older adults to be
      included in the analyses. Based on a framework analysis of our transcripts we
      identified three factors that facilitate physical activity in our sample, these
      include: 1) resourcefulness: engagement in self-help strategies such as self
      efficacy, self-control and adaptability; 2) social connections: the presence of
      relationships (friend, neighborhood, institutions) and social activities that
      support or facilitate high levels of physical activity; and 3) the role of the
      built and natural environments: features of places and spaces that support and
      facilitate high levels of physical activity. Findings provide insight into, and
      factors that facilitate older adults' physical activity. We discuss implications
      for programs (e.g., accessible community centers, with appropriate programming
      throughout the lifecourse) and policies geared towards the promotion of physical
      activity (e.g., the development of spaces that facilitate both physical and
      social activities).

PMID- 24300062
TI  - Shaping social situations: A hidden aspect of care work in nursing homes.
AB  - A significant aspect of care work in nursing homes involves dealing with
      emotional responses such as anxiety, fear, pain, depression and anger on the part
      of residents and their families. Previous care and nursing research on this topic
      centers around dyadic relationships and does not provide useful
      conceptualizations of how care workers actively deal with the social situations
      they encounter as part of their work. Drawing on ethnographic field work and
      interviews conducted in two Norwegian nursing homes, this article aims to
      describe and conceptualize a previously neglected aspect of good care work: the
      active shaping of social situations in order to lessen uneasy feelings of
      residents and their families. Three episodes of good work are described to
      illustrate how social situations can be shaped. Strategies include such actions
      as timing events, regulating one's presence, and composing social groups. The
      concluding section discusses some implications for nursing home management.

PMID- 24300061
TI  - Themes from older men's lay definitions of successful aging as indicators of
      primary and secondary control beliefs over time: The Manitoba Follow-up Study.
AB  - Constructs of control have theoretically been equated to successful aging in the
      psychology literature. Hence, we used themes from lay definitions of successful
      aging to quantify the prevalence of primary and secondary control beliefs over
      time. In doing so we hoped to shed new light upon the virtually uncharted area of
      older men's primary and secondary control beliefs over time. Using successful
      aging narratives spanning a 10-year timeframe from the Manitoba Follow-up Study
      cohort, we mapped themes from older men's lay definitions of successful aging
      onto Rothbaum, Weisz, and Snyder's (1982) constructs of primary and secondary
      control. We then examined the prevalence of the constructs of control over 10
      years and found that some men emphasized primary control, some emphasized
      secondary control, and others emphasized both, prospectively. Counter to what had
      previously been theorized, many older men continued to emphasize primary control
      as important well into late life. As expected, secondary control became more
      important with age. Furthermore, among those men who endorsed both primary and
      secondary control, significantly more men switched emphasis from primary to
      secondary control beliefs as they aged. This finding supported Rothbaum et al.'s
      (1982) surmise that individuals could switch from one type of control to another,
      presumably as life circumstances dictated. Knowing which types of control beliefs
      older men emphasize as they age has theoretical and practical implications.
      Theoretically, it sheds new light on the under-researched area of control beliefs
      in older men. Practically, it is informative for anyone interested in enhancing
      older men's perceptions of control in very late life, particularly in the face of
      otherwise uncontrollable age-related decline and imminent demise.

PMID- 24300063
TI  - A conceptual model for aging better together intentionally.
AB  - Social networks and improved health outcomes are strongly connected, yet many
      elders face isolation and loneliness. This article presents a study of an elder
      cohousing community in which residents are dealing with aging-related stresses as
      a group and creating positive outcomes for themselves. The article posits a
      conceptual model of how this phenomenon of "aging better together intentionally"
      occurs and the resulting benefits. QUESTIONS: What happens when elders choose to
      live together in a community in which they consciously address aging
      collectively? Is it possible to age better together intentionally? If so, what
      does it look like, under what circumstances does it blossom, and how does it
      improve the aging experience? METHODS: In-depth interviews were conducted with 26
      residents of an elder cohousing community in 2009. Respondents were white, mostly
      female, and averaged 73 years in age. Thematic analysis of interview transcripts
      led to a conceptual model of aging better together intentionally. To further
      explore the model, quantitative survey data were collected from the residents
      three years later. RESULTS: The framework of communal coping provided the
      mechanism of aging better together intentionally. Quantitative data supported the
      existence of mutual support, increased acceptance of aging, and feelings of
      safety/less worry/lessening of social isolation as benefits of this type of
      living arrangement. DISCUSSION: This research demonstrates the agency of older
      adults, the heterogeneity of the aging experience, and the value of older adults
      sharing their knowledge of the aging process with each other. Our conceptual
      model of aging better together intentionally could serve as a basis for
      interventions in other settings to provide a new way for people to age together
      with enhanced quality of life.

PMID- 24300064
TI  - Policies for older volunteers: A study of Germany and Italy, 1990-2008.
AB  - Older people increase their well-being and contribute to the community when they
      volunteer. Therefore, policy-makers sometimes consider supporting older
      volunteers. However, they reach different conclusions on whether they should
      introduce policies for older volunteers, and on what policy would be the most
      suitable. This article studies how policies for older volunteers emerged in
      Germany and Italy, both countries having one of the oldest populations in the
      world. It explores the political discourse on older volunteers, and how this
      discourse translates into policies. To do this, the article presents data
      collected in expert interviews and document analysis. Findings show that German
      policy-makers stress the contribution of volunteering to older people's well
      being and have introduced policies for older volunteers. Italian policy-makers,
      in contrast, frame older volunteers as social service providers and have decided
      not to single out specific age groups in their policies for volunteers. Moreover,
      the policies are influenced by the policy-makers' perceptions and path
      dependencies, meaning policies and institutions that were introduced in the past.
      These findings suggest that whether or not policies for older volunteers emerge
      depends less on the characteristics of the older population and more on the
      society and its political traditions.

PMID- 24300065
TI  - The legacy of Helena Znaniecka Lopata in widowhood research: Enduring concepts,
      life lessons, new insights.

PMID- 24300066
TI  - Lessons from history: Surviving old age during The Great Depression in the United
      States.
AB  - This paper focuses on 30 couples who received a pension and other services from
      two private trusts in Detroit, Michigan beginning in 1929 or 1930. Results of the
      qualitative analysis of case files, which contain notes recorded chronologically
      for 17 of the couples and then surviving spouses, provide a portrait of older
      couples' lives prior to a partner's death, circumstances surrounding the death,
      and changes in the social support systems of widows and widowers until their
      deaths. Close examination of the experiences of these couples is a reminder of
      how old age and widowhood were experienced prior to the enactment of public
      pensions and health insurance in the United States.

PMID- 24300067
TI  - Translating research findings into community based theatre: More than a dead
      man's wife.
AB  - Increasingly, qualitative scholars in health and social sciences are turning to
      innovative strategies as a way of translating research findings into informative,
      accessible and enjoyable forms for the community. The aim of this article is to
      describe how the research findings of a doctoral thesis - a narrative study about
      58 older women's experiences of widowhood - were translated into a unique and
      professionally developed script to form the basis for a successful theatrical
      production that has travelled extensively within Australia. This article reports
      on the process of collaboration between a researcher, a highly regarded
      Australian actor/script writer and an ensemble of well-known and experienced
      professional actors. Together the collaborating partners translated the research
      data and findings about growing older and 'widowhood' into a high quality theatre
      production. In particular, we argue in this paper that research-based theatre is
      an appropriate medium for communicating research findings about important life
      issues of concern to older people in a safe, affirming and entertaining manner.
      By outlining the process of translating research findings into theatre we hope to
      show that there is a real value in this translation approach for both researcher
      and audience alike.

PMID- 24300068
TI  - Dating after late-life spousal loss: Does it compromise relationships with adult
      children?
AB  - In Widowhood in an American City (1973), Helena Lopata observed that widows
      struggle with new romantic relationships because their children often are
      resentful toward these new partners. Since the publication of Lopata's classic
      work, however, few studies have explored empirically the ways that widow(er)'s
      dating affects their relationships with children. We use prospective data from
      the Changing Lives of Older Couples study (CLOC) to explore: (1) the impact of
      bereaved spouses' dating on positive and negative aspects of parent-child
      relationships six and 18 months postloss; (2) the extent to which these
      associations are explained by preloss characteristics; and (3) the factors that
      moderate the association between widow(er) dating and parent-child relations.
      Multivariate analyses show that widowers who are interested in dating six months
      postloss report low levels of support and high levels of conflict with their
      children, yet widows report enhanced relationship quality. This pattern reflects
      the fact that men who are interested in dating do form new relationships, whereas
      women's interests are not translated into actual dating. Widowers' dating six
      months postloss compromises parent-child closeness among those with a history of
      strained parent-child relations, yet enhances closeness among those with
      historically good relationships. Dating takes a harsher toll on parent-daughter
      compared to parent-son relationships. Overall, dating threatens parent-child
      relationships in specific cases, yet it may also strengthen widow(er) s' parent
      child bonds. We discuss the implications for the well-being of older widow(er)s
      and adult children.

PMID- 24300069
TI  - "You're not getting married for the moon and the stars": The uncertainties of
      older British widowers about the idea of new romantic relationships.
AB  - Older widowers are more likely to remarry than older widowed women. However,
      relatively little is known about the attitudes of older widowers to new romantic
      relationships and remarriage or repartnering. In this study of 60 widowers, more
      than half spontaneously discussed their attitudes toward, and experiences of,
      these relationships. However, none of the widowers had remarried and of those who
      described themselves as repartnered only one was cohabiting. We examine these
      data in the light of Lopata's concept of 'husband sanctification' (1981). We
      identify four themes. First, some widowers do sanctify their late wives. Second,
      we argue that wife sanctification contributes to widowers' uncertainties about
      repartnering. Third, when widowers make decisions to repartner, wife
      sanctification does not appear to make an important contribution. Finally, there
      is evidence to suggest that wife sanctification influences how men refer to their
      new women friends. Thus, we conclude by arguing that wife sanctification
      influences widowers' decisions surrounding remarriage/repartnering.

PMID- 24300070
TI  - Ethno-cultural diversity in the experience of widowhood in later life: Chinese
      widows in Canada.
AB  - This paper utilizes Helena Znaniecka Lopata's concept of life frameworks as a
      lens through which to understand the experience of widowhood amongst elderly
      Chinese immigrant women living in Toronto, Canada. While Lopata defined life
      frameworks as including social supports, social relations and social roles, for
      these widows, personal resources (framed in Chinese cultural context) were also
      important aspects of life frameworks. In-depth interviews with 20 widows
      contacted through a Chinese community center were conducted in Mandarin and
      Cantonese and then transcribed and interpreted through team-based qualitative
      analyses. These women ranged in age from 69 to 93 years and had been in Canada an
      average of 17 years, with over half of them widowed following immigration. Our
      analysis framed the widows' narratives in terms of four types of supports defined
      by Lopata: social, service, financial and emotional supports. They had fairly
      extensive social and service supports focused primarily around family and the
      Chinese community. Although norms of filial piety traditionally dictate sons as
      primary supports, daughters predominated as providers of supports to these
      widows. Interpreted from a life course perspective, financial supports were
      deemed sufficient, despite overall limited financial means. Emotional support was
      more nuanced and complex for these widows. Loneliness and feelings of social
      isolation were prevalent. Nevertheless, themes of acceptance and satisfaction
      dominated our findings, as did reciprocity and exchange. The narrative accounts
      of these widows depict a complexity of experience rooted in their biographies as
      Chinese women and as immigrants, rather than primarily in widowhood itself.

PMID- 24300071
TI  - A comparison of widowhood and well-being among older Greek and British-Australian
      migrant women.
AB  - The impact of widowhood on well-being has been well-documented, but to date has
      not focused extensively on the experience of older migrants who have aged in a
      foreign land. This study aimed to examine the well-being of older migrant widows
      from two groups in South Australia: British-born (n=61) and Greek-born (n=60)
      Australian migrants, who had been widowed, on average, 13 years. All participants
      completed a self-report questionnaire in their preferred language. Three
      indicators of current well-being (self-rated health, depression and loneliness)
      as well as variables expected to differ cross-culturally, and potentially
      influence well-being (mourning rituals; continuing bonds to one's spouse;
      religiosity; social support) were measured. Greek-born widows displayed higher
      levels of mourning rituals, continuing bonds and religiosity than the British.
      Both groups perceived similarly high levels of familial social support. Greek
      widows also reported worse self-rated health, and increased symptoms of
      depression and loneliness compared to the British. This paper suggests that the
      detrimental impact of widowhood on well-being may be greater for non-English
      speaking migrants who are ageing outside of their country of origin, and who,
      despite residing in an English-speaking host country for several decades, have
      retained the linguistic, cultural and religious practices and traditions of their
      home country.

PMID- 24300072
TI  - A cross-cultural comparison of health behaviors between Saudi and British
      adolescents living in urban areas: gender by country analyses.
AB  - This study investigated the cross-cultural differences and similarity in health
      behaviors between Saudi and British adolescents. A school-based cross-sectional
      study was conducted at four cities in Saudi Arabia (Riyadh and Al-Khobar; N =
      1,648) and Britain (Birmingham and Coventry; N = 1,158). The participants (14-18
      year-olds) were randomly selected using a multistage stratified cluster sampling
      technique. Measurements included anthropometric, screen time, validated physical
      activity (PA) questionnaire and dietary habits. The overweight/obesity prevalence
      among Saudi adolescents (38.3%) was significantly (p < 0.001) higher than that
      found among British adolescents (24.1%). The British adolescents demonstrated
      higher total PA energy expenditure than Saudi adolescents (means +/- SE = 3,804.8
      +/- 81.5 vs. 2,219.9 +/- 65.5 METs-min/week). Inactivity prevalence was
      significantly (p < 0.001) higher among Saudi adolescents (64%) compared with that
      of British adolescents (25.5%). The proportions of adolescents exceeding 2 h of
      daily screen time were high (88.0% and 90.8% among Saudis and British,
      respectively). The majority of Saudi and British adolescents did not have daily
      intakes of breakfast, fruit, vegetables and milk. MANCOVA showed significant (p <
      0.05) gender by country interactions in several lifestyle factors. There was a
      significant (p < 0.001) gender differences in the ratio of physical activity to
      sedentary behaviors. In conclusion, Saudi and British adolescents demonstrated
      some similarities and differences in their PA levels, sedentary behaviors and
      dietary habits. Unhealthy lifestyle behaviors among adolescents appear to be a
      cross-cultural phenomenon. 

PMID- 24300073
TI  - Risk factors, health effects and behaviour in older people during extreme heat: a
      survey in South Australia.
AB  - Older people had a high incidence of hospitalisation during the 2009 heat wave in
      South Australia. We sought to explore resilience, behaviours, health risk factors
      and health outcomes during recent heat waves for a representative sample of
      independently living residents. A telephone survey of 499 people aged 65 years
      and over was conducted, and included both metropolitan and rural residences. A
      variety of adaptive strategies were reported, with 75% maintaining regular
      appointments and activities during the heat. However, 74% took medication for
      chronic disease and 25% assessed their health status to be fair to poor. In a
      multivariate model, factors associated with heat health outcomes included
      medication for mental health, heart failure, diabetes or respiratory health,
      reporting a reduced health status, use of mobility aids and being female.
      Compared with younger participants, those over 75 had more check-up calls and
      visits by family, friends and neighbours. However, confidence to call on support
      was associated with indicators of social isolation. The study indicates that
      older people are generally resilient, but interventions addressing multi
      morbidity and medication interactions and social isolation should be developed. 

PMID- 24300074
TI  - Projected heat-related mortality in the U.S. urban northeast.
AB  - Increased heat-related mortality is projected to be among the major impacts of
      climate change on human health, and the United States urban Northeast region is
      likely to be particularly vulnerable. In support of regional adaptation planning,
      quantitative information is needed on potential future health responses at the
      urban and regional scales. Here, we present future projections of heat-related
      mortality in Boston, New York and Philadelphia utilizing downscaled next
      generation climate models and Representative Concentration Pathways (RCPs)
      developed in support of the Intergovernmental Panel on Climate Change (IPCC)'s
      Fifth Assessment Report (AR5). Our analyses reveal that heat-related mortality
      rates per 100,000 of population during the baseline period between 1985 and 2006
      were highest in Philadelphia followed by New York City and Boston. However,
      projected heat-related mortality rates in the 2020s, 2050s and 2080s were highest
      in New York City followed by Philadelphia and Boston. This study may be of value
      in developing strategies for reducing the future impacts of heat and building
      climate change resilience in the urban Northeast region. 

PMID- 24300075
TI  - A microfluidic device for continuous sensing of systemic acute toxicants in
      drinking water.
AB  - A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking
      water was designed and fabricated. The system employed Vibrio fischeri cells as
      broad-spectrum sensors to monitor potential systemic cell toxicants in water,
      such as heavy metal ions and phenol. Specifically, the chip was designed for
      continuous detection. The chip design included two counter-flow micromixers, a T
      junction droplet generator and six spiral microchannels. The cell suspension and
      water sample were introduced into the micromixers and dispersed into droplets in
      the air flow. This guaranteed sufficient oxygen supply for the cell sensors.
      Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were
      selected as typical toxicants to validate the sensing system. Preliminary tests
      verified that the system was an effective screening tool for acute toxicants
      although it could not recognize or quantify specific toxicants. A distinct non
      linear relationship was observed between the zinc ion concentration and the
      Relative Luminescence Units (RLU) obtained during testing. Thus, the
      concentration of simple toxic chemicals in water can be roughly estimated by this
      system. The proposed device shows great promise for an early warning system for
      water safety. 

PMID- 24300076
TI  - Using continuous data tracking technology to study exercise adherence in
      pulmonary rehabilitation.
AB  - Pulmonary rehabilitation (PR) is an important component in the management of
      respiratory diseases. The effectiveness of PR is dependent upon adherence to
      exercise training recommendations. The study of exercise adherence is thus a key
      step towards the optimization of PR programs. To date, mostly indirect measures,
      such as rates of participation, completion, and attendance, have been used to
      determine adherence to PR. The purpose of the present protocol is to describe how
      continuous data tracking technology can be used to measure adherence to a
      prescribed aerobic training intensity on a second-by-second basis. In our
      investigations, adherence has been defined as the percent time spent within a
      specified target heart rate range. As such, using a combination of hardware and
      software, heart rate is measured, tracked, and recorded during cycling second-by
      second for each participant, for each exercise session. Using statistical
      software, the data is subsequently extracted and analyzed. The same protocol can
      be applied to determine adherence to other measures of exercise intensity, such
      as time spent at a specified wattage, level, or speed on the cycle ergometer.
      Furthermore, the hardware and software is also available to measure adherence to
      other modes of training, such as the treadmill, elliptical, stepper, and arm
      ergometer. The present protocol, therefore, has a vast applicability to directly
      measure adherence to aerobic exercise. 

PMID- 24300077
TI  - Cell squeezing as a robust, microfluidic intracellular delivery platform.
AB  - Rapid mechanical deformation of cells has emerged as a promising, vector-free
      method for intracellular delivery of macromolecules and nanomaterials. This
      technology has shown potential in addressing previously challenging applications;
      including, delivery to primary immune cells, cell reprogramming, carbon nanotube,
      and quantum dot delivery. This vector-free microfluidic platform relies on
      mechanical disruption of the cell membrane to facilitate cytosolic delivery of
      the target material. Herein, we describe the detailed method of use for these
      microfluidic devices including, device assembly, cell preparation, and system
      operation. This delivery approach requires a brief optimization of device type
      and operating conditions for previously unreported applications. The provided
      instructions are generalizable to most cell types and delivery materials as this
      system does not require specialized buffers or chemical modification/conjugation
      steps. This work also provides recommendations on how to improve device
      performance and trouble-shoot potential issues related to clogging, low delivery
      efficiencies, and cell viability. 

PMID- 24300078
TI  - Induction of invasive transitional cell bladder carcinoma in immune intact human
      MUC1 transgenic mice: a model for immunotherapy development.
AB  - A preclinical model of invasive bladder cancer was developed in human mucin 1
      (MUC1) transgenic (MUC1.Tg) mice for the purpose of evaluating immunotherapy
      and/or cytotoxic chemotherapy. To induce bladder cancer, C57BL/6 mice (MUC1.Tg
      and wild type) were treated orally with the carcinogen N-butyl-N-(4
      hydroxybutyl)nitrosamine (OH-BBN) at 3.0 mg/day, 5 days/week for 12 weeks. To
      assess the effects of OH-BBN on serum cytokine profile during tumor development,
      whole blood was collected via submandibular bleeds prior to treatment and every
      four weeks. In addition, a MUC1-targeted peptide vaccine and placebo were
      administered to groups of mice weekly for eight weeks. Multiplex fluorometric
      microbead immunoanalyses of serum cytokines during tumor development and
      following vaccination were performed. At termination, interferon gamma (IFN
      gamma)/interleukin-4 (IL-4) ELISpot analysis for MUC1 specific T-cell immune
      response and histopathological evaluations of tumor type and grade were
      performed. The results showed that: (1) the incidence of bladder cancer in both
      MUC1.Tg and wild type mice was 67%; (2) transitional cell carcinomas (TCC)
      developed at a 2:1 ratio compared to squamous cell carcinomas (SCC); (3)
      inflammatory cytokines increased with time during tumor development; and (4)
      administration of the peptide vaccine induces a Th1-polarized serum cytokine
      profile and a MUC1 specific T-cell response. All tumors in MUC1.Tg mice were
      positive for MUC1 expression, and half of all tumors in MUC1.Tg and wild type
      mice were invasive. In conclusion, using a team approach through the coordination
      of the efforts of pharmacologists, immunologists, pathologists and molecular
      biologists, we have developed an immune intact transgenic mouse model of bladder
      cancer that expresses hMUC1. 

PMID- 24300079
TI  - Measurement of total calcium in neurons by electron probe X-ray microanalysis.
AB  - In this article the tools, techniques, and instruments appropriate for
      quantitative measurements of intracellular elemental content using the technique
      known as electron probe microanalysis (EPMA) are described. Intramitochondrial
      calcium is a particular focus because of the critical role that mitochondrial
      calcium overload plays in neurodegenerative diseases. The method is based on the
      analysis of X-rays generated in an electron microscope (EM) by interaction of an
      electron beam with the specimen. In order to maintain the native distribution of
      diffusible elements in electron microscopy specimens, EPMA requires
      "cryofixation" of tissue followed by the preparation of ultrathin cryosections.
      Rapid freezing of cultured cells or organotypic slice cultures is carried out by
      plunge freezing in liquid ethane or by slam freezing against a cold metal block,
      respectively. Cryosections nominally 80 nm thick are cut dry with a diamond knife
      at ca. -160  degrees C, mounted on carbon/pioloform-coated copper grids, and
      cryotransferred into a cryo-EM using a specialized cryospecimen holder. After
      visual survey and location mapping at <=-160  degrees C and low electron dose,
      frozen-hydrated cryosections are freeze-dried at -100  degrees C for ~30 min.
      Organelle-level images of dried cryosections are recorded, also at low dose, by
      means of a slow-scan CCD camera and subcellular regions of interest selected for
      analysis. X-rays emitted from ROIs by a stationary, focused, high-intensity
      electron probe are collected by an energy-dispersive X-ray (EDX) spectrometer,
      processed by associated electronics, and presented as an X-ray spectrum, that is,
      a plot of X-ray intensity vs. energy. Additional software facilitates: 1)
      identification of elemental components by their "characteristic" peak energies
      and fingerprint; and 2) quantitative analysis by extraction of peak
      areas/background. This paper concludes with two examples that illustrate typical
      EPMA applications, one in which mitochondrial calcium analysis provided critical
      insight into mechanisms of excitotoxic injury and another that revealed the basis
      of ischemia resistance. 

PMID- 24300080
TI  - Working wonders? investigating insight with magic tricks.
AB  - We propose a new approach to differentiate between insight and noninsight problem
      solving, by introducing magic tricks as problem solving domain. We argue that
      magic tricks are ideally suited to investigate representational change, the key
      mechanism that yields sudden insight into the solution of a problem, because in
      order to gain insight into the magicians' secret method, observers must overcome
      implicit constraints and thus change their problem representation. In Experiment
      1, 50 participants were exposed to 34 different magic tricks, asking them to find
      out how the trick was accomplished. Upon solving a trick, participants indicated
      if they had reached the solution either with or without insight. Insight was
      reported in 41.1% of solutions. The new task domain revealed differences in
      solution accuracy, time course and solution confidence with insight solutions
      being more likely to be true, reached earlier, and obtaining higher confidence
      ratings. In Experiment 2, we explored which role self-imposed constraints
      actually play in magic tricks. 62 participants were presented with 12 magic
      tricks. One group received verbal cues, providing solution relevant information
      without giving the solution away. The control group received no informative cue.
      Experiment 2 showed that participants' constraints were suggestible to verbal
      cues, resulting in higher solution rates. Thus, magic tricks provide more
      detailed information about the differences between insightful and noninsightful
      problem solving, and the underlying mechanisms that are necessary to have an
      insight. 

PMID- 24300081
TI  - Oesophageal foreign body: an unusual presentation.
AB  - OBJECTIVE: This paper describes and discusses the case of an oesophageal foreign
      body, in which the patient presented with primarily respiratory clinical signs.
      CASE REPORT: A 17-month-old child, who had ingested a watch battery, presented to
      emergency services on multiple occasions with upper respiratory tract symptoms.
      Subsequent radiographs showed the battery in the oesophagus impinging on the
      trachea. The battery was removed successfully under a general anaesthetic.
      CONCLUSION: Large oesophageal foreign bodies can impinge on the trachea causing
      upper respiratory tract signs. In such cases, anteroposterior and lateral chest
      films are imperative to make a correct diagnosis.

PMID- 24300082
TI  - Measuring the needs of mental health patients in Greece: reliability and validity
      of the Greek version of the Camberwell assessment of need.
AB  - BACKGROUND: Evaluation of mental health services based on patients' needs
      assessments has never taken place in Greece, although it is a crucial factor for
      the efficient use of their limited resources. AIM: To examine the inter-rater and
      test-retest reliability and the concurrent/convergent validity of the Greek
      research version of the Camberwell Assessment of Need-Research (CAN-R). METHOD: A
      total of 53 schizophrenic patient-staff pairs were interviewed twice to test the
      inter-rater and test-retest reliability of the Greek version of the CAN-R. The
      World Health Organization Quality of Life-Brief Form (WHOQOL-BREF) and World
      Health Organization Disability Assessment Schedule-2.0 (WHODAS-2.0) were
      administered to the patients to examine concurrent validity. RESULTS: The inter
      rater and test-retest reliability of patient and staff interviews for the 22
      individual items and the eight summary scores of the instrument's four sections
      were good to excellent. Significant correlations emerged between CAN scores and
      the WHOQOL-BREF and WHODAS-2.0 domains for both patient and staff ratings,
      indicating good concurrent validity. CONCLUSION: Our results suggest that the
      Greek version of the CAN-R is a reliable instrument for assessing mental health
      patients' needs. Moreover, it is the first CAN-R validity study with satisfactory
      results using WHOQOL-BREF and WHODAS-2.0 as criterion variables.

PMID- 24300083
TI  - Frequency of perinatal depression in Serbia and associated risk factors.
AB  - OBJECTIVE: To screen 212 women for depression symptoms during pregnancy and
      postpartum in Serbia. METHODS: Questionnaires that covered key demographic and
      obstetric information and Edinburgh Postnatal Depression Scale (EPDS) were
      administered at the third trimester of pregnancy and at 8 weeks postpartum.
      RESULTS: In all, 21% of the sample was screened as depression positive during
      pregnancy. Subsequently, efforts were made to follow up 195 women through
      postpartum. Of the 195 women, 11% were screened positive during postpartum. Risk
      factors were low education level, low satisfaction with financial situation, high
      risk pregnancy and depression during pregnancy. Logistic regression with backward
      elimination showed that women who had high-risk pregnancy have threefold
      increased risk of postpartum depression, and women who had antenatal depressive
      symptoms have 10-fold increased risk of postpartum depression. CONCLUSION: In
      countries where screening tool for depression is not applied routinely in
      obstetrics settings, clinicians should be aware of risk factors, frequency and
      level of depressive symptoms during pregnancy and postpartum.

PMID- 24300084
TI  - Frontal gamma noise power and cognitive domains in schizophrenia.
AB  - The cognitive deficit profile is different among individuals with schizophrenia.
      We quantified the amount of electroencephalographic activity unlocked to stimuli
      onset (noise power) over frontal regions regarding deficit in cognitive domains.
      Forty-six patients with schizophrenia and 27 healthy controls underwent clinical,
      cognitive and electrophysiological assessments. Noise power studies may be
      considered complementary but not equivalent to induced power studies. We compared
      gamma and theta noise power magnitude during a P300 paradigm between subsets of
      patients divided according to cognitive deficit in key domains and controls.
      Patients displayed higher gamma noise power activity at Fz site and significantly
      lower performance in all cognitive domains when compared to controls. The subset
      of patients with cognitive deficit for working memory and problem
      solving/executive functions domains displayed significantly higher frontal
      lateral noise power values in comparison to the subset of patients without
      cognitive deficit and controls. Patients with significant cognitive deficits in
      domains with greater frontal contribution are also characterized by an abnormally
      higher gamma band noise power over the frontal region. Our data may endorse
      various biological subsets within schizophrenia, characterized by the presence or
      absence of a significant cognitive deficit in frontal domains. 

PMID- 24300085
TI  - Resting-state synchrony between anterior cingulate cortex and precuneus relates
      to body shape concern in anorexia nervosa and bulimia nervosa.
AB  - Cortical areas supporting cognitive control and salience demonstrate different
      neural responses to visual food cues in patients with eating disorders. This top
      down cognitive control, which interacts with bottom-up appetitive responses, is
      tightly integrated not only in task conditions but also in the resting-state. The
      dorsal anterior cingulate cortex (dACC) is a key node of a large-scale network
      that is involved in self-referential processing and cognitive control. We
      investigated resting-state functional connectivity of the dACC and hypothesized
      that altered connectivity would be demonstrated in cortical midline structures
      involved in self-referential processing and cognitive control. Seed-based resting
      state functional connectivity was analyzed in women with anorexia nervosa (N=18),
      women with bulimia nervosa (N=20) and age matched healthy controls (N=20).
      Between group comparisons revealed that the anorexia nervosa group exhibited
      stronger synchronous activity between the dACC and retrosplenial cortex, whereas
      the bulimia nervosa group showed stronger synchronous activity between the dACC
      and medial orbitofrontal cortex. Both groups demonstrated stronger synchronous
      activity between the dACC and precuneus, which correlated with higher scores of
      the Body Shape Questionnaire. The dACC-precuneus resting-state synchrony might be
      associated with the disorder-specific rumination on eating, weight and body shape
      in patients with eating disorders. 

PMID- 24300086
TI  - A comparative diffusion tensor imaging study of corpus callosum subregion
      integrity in bipolar disorder and schizophrenia.
AB  - Structural magnetic resonance imaging (MRI) studies have provided evidence for
      corpus callosum (CC) white matter abnormalities in bipolar disorder (BD) and
      schizophrenia (SZ). These findings include alterations in shape, volume, white
      matter intensity and structural integrity compared to healthy control
      populations. Although CC alterations are implicated in both SZ and BD, no study
      of which we are aware has investigated callosal subregion differences between
      these two patient populations. We used diffusion tensor imaging (DTI) to assess
      CC integrity in patients with BD (n=16), SZ (n=19) and healthy controls (HC)
      (n=24). Fractional anisotropy (FA) of CC subregions was measured using region of
      interest (ROI) analysis and compared in the three groups. Significant group
      differences of FA values were revealed in five CC subregions, including the
      anterior genu, middle genu, posterior genu, posterior body and anterior splenium.
      FA values of the same subregions were significantly reduced in patients with SZ
      compared with HC. FA values were also significantly reduced in patients with BD
      compared to the HC group in the same subregions, excepting the middle genu. No
      significant difference was found between patient groups in any region. Most of
      the alterations in CC subregions were present in both the BD and SZ groups. These
      results imply an overlap in potential pathology, possibly relating to risk
      factors common to both disorders. The one region that differed between patient
      groups, the middle genu area, may serve as an illness marker and is perhaps
      involved in the different cognitive impairments observed in BD and SZ. 

PMID- 24300087
TI  - Preparation of monodispersed macroporous core-shell molecularly imprinted
      particles and their application in the determination of 2,4-dichlorophenoxyacetic
      acid.
AB  - Porous polymers have aroused extensive attention due to their controllable porous
      structure in favor of mass transfer and binding capacity. In this work, the novel
      macroporous core-shell molecularly imprinted polymers (MIP) for selective
      recognition of 2,4-dichlorophenoxyacetic acid (2,4-D) were prepared by surface
      initiated atom transfer radical polymerization (si-ATRP). By using one-step
      swelling and polymerization method, the monodispersed macroporous poly(glycidyl
      methacrylate) (PGMA) particles were synthesized and used as supporting matrix for
      preparing surface MIP particles (PGMA@MIP). Thanks to the inner and outer surface
      located binding cavities and the macroporous structure, the PGMA@MIPs revealed
      desirable efficiency for template removal and mass transfer, and thus excellent
      accessibility and affinity toward template 2,4-D. Moreover, PGMA@MIPs exhibited
      much higher selectivity toward 2,4-D than PGMA@NIPs. PGMA@MIP particles were
      directly used to selectively enrich 2,4-D from tap water and the recoveries of
      2,4-D were obtained as 90.0-93.4% with relative standard division of 3.1-3.4%
      (n=3). The macroporous PGMA@MIPs also possessed steady and excellent reusable
      performance for 2,4-D in four extraction/stripping cycles. This novel macroporous
      core-shell imprinted material may become a powerful tool for rapid and efficient
      enrichment and separation of target compounds from the complicated samples. 

PMID- 24300088
TI  - Measurements of association constants between enantiomers and chiral selectors by
      capillary gas chromatography. Theoretical and practical considerations.
AB  - The association constants of several volatile enantiomers with octakis(3-O
      butanoyl-2,6-di-O-pentyl)-gamma-cyclodextrin at temperatures between 50 and 100 
      degrees C were measured by gas-liquid chromatography using capillary columns
      coated with different amounts of chiral selector dissolved in polysiloxane OV
      1701 and prepared with a precisely determined phase ratio. Simple expressions
      were deduced to estimate the apparent distribution constants from accurate hold
      up and retention times along with that known phase ratio at each temperature. The
      enantiomer-chiral selector association constants were then calculated from the
      linear regression of the apparent constants as a function of the chiral selector
      concentration. One aim of this study consisted in discussing all the experimental
      uncertainties inherent in the determination of enantiomer/selector association
      constants with chiral analytes, and how these fundamental measurements can be
      performed precisely without resorting to the use of reference solutes.

PMID- 24300089
TI  - Size exclusion chromatography of polysaccharides with reverse phase liquid
      chromatography.
AB  - This work describes the use of a reverse phase (RP) column for size-based
      separation of hydrophilic polysaccharides. The entire separation window (before
      and after void volume) is used to provide unique separation of polysaccharides
      from other components in a glycol-conjugate vaccine or complex media of
      fermentation broth. The technique has also been applied to the separation of
      polysaccharides of different sizes. The effect of chromatographic parameters
      including type of packing material (CN, C8 and C18), pore size (80 and 300A) of
      stationary phase, concentration of organic solvent on the separation was
      investigated. In addition, characterization of size-based separation was
      evaluated by coupling of RP column with multi-angle laser light scattering
      (MALLs) detector. 

PMID- 24300091
TI  - Hepatic resection for metastatic melanoma: a systematic review.
AB  - Melanoma metastatic to the liver has a very poor prognosis, and has traditionally
      been treated using systemic chemotherapy with limited efficacy. Surgery is
      increasingly being explored as a therapeutic option for melanoma liver
      metastases, with varying levels of success. A systematic review was undertaken to
      explore the short-term and long-term outcomes associated with hepatectomy for
      melanoma metastases, in addition to identifying prognostic factors favouring
      increased survival. All eligible studies were identified through an electronic
      search of Medline and Embase (January 1990-March 2013). Each study was
      independently analysed by two reviewers, with relevant data extracted and
      tabulated according to predetermined criteria. Thirteen studies were selected
      that fulfilled the selection criteria, with a total of 551 patients undergoing
      hepatic resection for melanoma metastases. Metastases to the liver occurred at a
      median interval of 54 months. The median perioperative morbidity and mortality
      were 10% (range 0-28.6%) and 0% (range 0-7.1%), respectively. The median overall
      survival for operative patients was 24 months, with median survival being greater
      in the R0 resection group (25 months; range 9.5-65.6 months) compared with the
      R1/2 resection group (16 months; range 11.7-29 months). Overall median 1-, 3- and
      5-year survival rates were 70% (range 39-100%), 36% (range 10.2-53%) and 24%
      (range 3-53%), respectively. Positive prognostic factors may include single
      hepatic metastases, a longer time to development of hepatic metastases and R0
      resection. Hepatic resection for metastatic melanoma might confer a distinct
      survival benefit in a select group of patients, although disease recurrence is
      the norm. 

PMID- 24300090
TI  - Enhanced in-vitro and in-vivo suppression of A375 melanoma by combined IL-24/OSM
      adenoviral-mediated gene therapy.
AB  - Interleukin-24 (IL-24)/melanoma differentiation-associated gene-7 (mda-7) is a
      unique cytokine-tumor suppressor that displays ubiquitous antitumor properties
      and tumor-specific killing activity. Oncostatin M (OSM) is the most active IL-6
      type cytokine and inhibits the proliferation of various solid tumor cell lines.
      Multigene-based combination therapy may be an effective practice in cancer gene
      therapy. The therapeutic potential of a combination of IL-24 and OSM in treating
      cancers is still elusive. In this study, we aimed to examine the enhanced
      antitumor activity of adenovirus-mediated IL-24/OSM tumor suppressor gene
      cotransfer in human melanoma cells. We constructed an IL-24/OSM bicistronic
      adenovirus and assessed its combined effect on A375 human melanoma cells in vitro
      and in vivo by detecting and comparing apoptosis in the bicistronic antioncogene
      group (Ad-IL-24-OSM) and in the IL-24 or OSM single antioncogene group. We also
      investigated the possible mechanism underlying this effect. The bicistronic
      adenovirus-mediated coexpression of IL-24 and OSM induced additive growth
      suppression and apoptosis and an overlapping effect on the upregulation of p21,
      p53, Bax, and cleaved caspase-3 in vitro and in vivo. Moreover, Ad-IL-24-OSM
      treatment additively reduced the expression of CDK4 and cyclin D1 in A375
      melanoma cells and the expression of CD34 and Cox-2 in A375 xenograft tumors in
      athymic nude mice. The enhanced antitumor activity elicited by Ad-IL-24-OSM was
      closely associated with the activation of the apoptotic pathway and the additive
      inhibition of tumor angiogenesis. Therefore, our results indicate that cancer
      gene therapy combining two or more tumor suppressors, such as IL-24 and OSM, may
      constitute a novel and effective therapeutic strategy for treating malignant
      melanoma and other cancers. 

PMID- 24300092
TI  - Action mechanisms of Liver X Receptors.
AB  - The two Liver X Receptors, LXRalpha and LXRbeta, are nuclear receptors belonging
      to the superfamily of ligand-activated transcription factors. They share more
      than 78% homology in amino acid sequence, a common profile of oxysterol ligands
      and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial
      roles in several metabolic pathways: lipid metabolism, in particular in
      preventing cellular cholesterol accumulation; glucose homeostasis; inflammation;
      central nervous system functions and water transport. As with all nuclear
      receptors, the transcriptional activity of LXR is the result of an orchestration
      of numerous cellular factors including ligand bioavailability, presence of
      corepressors and coactivators and cellular context i.e., what other pathways are
      activated in the cell at the time the receptor recognizes its ligand. In this
      mini-review we summarize the factors regulating the transcriptional activity and
      the mechanisms of action of these two receptors. 

PMID- 24300093
TI  - Nucleofection of rodent neuroblasts to study neuroblast migration in vitro.
AB  - The subventricular zone (SVZ) located in the lateral wall of the lateral
      ventricles plays a fundamental role in adult neurogenesis. In this restricted
      area of the brain, neural stem cells proliferate and constantly generate
      neuroblasts that migrate tangentially in chains along the rostral migratory
      stream (RMS) to reach the olfactory bulb (OB). Once in the OB, neuroblasts switch
      to radial migration and then differentiate into mature neurons able to
      incorporate into the preexisting neuronal network. Proper neuroblast migration is
      a fundamental step in neurogenesis, ensuring the correct functional maturation of
      newborn neurons. Given the ability of SVZ-derived neuroblasts to target injured
      areas in the brain, investigating the intracellular mechanisms underlying their
      motility will not only enhance the understanding of neurogenesis but may also
      promote the development of neuroregenerative strategies. This manuscript
      describes a detailed protocol for the transfection of primary rodent RMS
      postnatal neuroblasts and the analysis of their motility using a 3D in vitro
      migration assay recapitulating their mode of migration observed in vivo. Both rat
      and mouse neuroblasts can be quickly and efficiently transfected via
      nucleofection with either plasmid DNA, small hairpin (sh)RNA or short interfering
      (si)RNA oligos targeting genes of interest. To analyze migration, nucleofected
      cells are reaggregated in 'hanging drops' and subsequently embedded in a three
      dimensional matrix. Nucleofection per se does not significantly impair the
      migration of neuroblasts. Pharmacological treatment of nucleofected and
      reaggregated neuroblasts can also be performed to study the role of signaling
      pathways involved in neuroblast migration. 

PMID- 24300094
TI  - Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor
      prognosis. Multiple pathological processes, including inflammation, epithelial
      mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in
      the pathogenesis of IPF. Recent findings suggested that nuclear factor-kappaB (NF
      kappaB) is constitutively activated in IPF and acts as a central regulator in the
      pathogenesis of IPF. The aim of our study was to reveal the value of
      andrographolide on bleomycin-induced inflammation and fibrosis in mice. The
      indicated dosages of andrographolide were administered in mice with bleomycin
      induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages,
      neutrophils and lymphocytes, alone with TNF-alpha in bronchoalveolar lavage fluid
      (BALF) were measured. HE staining and Masson's trichrome (MT) staining were used
      to observe the histological alterations of lungs. The Ashcroft score and
      hydroxyproline content of lungs were also measured. TGF-beta1 and alpha-SMA mRNA
      and protein were analyzed. Activation of NF-kappaB was determined by western
      blotting and electrophoretic mobility shift assay (EMSA). On day 21 after
      bleomycin stimulation, andrographolide dose-dependently inhibited the
      inflammatory cells and TNF-alpha in BALF. Meanwhile, our data demonstrated that
      the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung
      were reduced by andrographolide administration. Furthermore, andrographloide
      suppressed TGF-beta1 and alpha-SMA mRNA and protein expression in bleomycin
      induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose
      dependently inhibited the ratio of phospho-NF-kappaB p65/total NF-kappaB p65 and
      NF-kappaB p65 DNA binding activities. Our findings indicate that andrographolide
      compromised bleomycin-induced pulmonary inflammation and fibrosis possibly
      through inactivation of NF-kappaB. Andrographolide holds promise as a novel drug
      to treat the devastating disease of pulmonary fibrosis. 

PMID- 24300095
TI  - New mononuclear Cu(II) complexes and 1D chains with 4-amino-4H-1,2,4-triazole.
AB  - The crystal structures of two mononuclear Cu(II) NH2trz complexes
      [Cu(NH2trz)4(H2O)](AsF6)2 (I) and [Cu(NH2trz)4(H2O)](PF6)2 (II) as well as two
      coordination polymers [Cu(MU2-NH2trz)2Cl]Cl?H2O (III) and [Cu(MU2-NH2trz)2Cl]
      (SiF6)0.5?1.5H2O (IV) are presented. Cationic 1D chains with bridging bis
      monodentate MU2-coordinated NH2trz and bridging MU2-coordinated chloride ligands
      are present in III and IV. In these coordination polymers, the Cu(II) ions are
      strongly antiferromagnetically coupled with J=-128.4 cm(-1) for III and J=-143
      cm(-1) for IV (H=-JSigmaSiSi+1), due to the nature of the bridges between spin
      centers. Inter-chain interactions present in the crystal structures were taken
      into consideration, as well as g factors, which were determined experimentally,
      for the quantitative modeling of their magnetic properties.

PMID- 24300097
TI  - Colorectal laterally spreading tumors by computed tomographic colonography.
AB  - To date, few reports focused primarily on detecting colorectal laterally
      spreading tumors (LSTs) have been published. The aim of this study was to
      determine the visibility of LSTs on computed tomographic colonography (CTC)
      compared with that on colonoscopy as a standard. We retrospectively reviewed and
      matched data on endoscopic and CTC reports in 157 patients (161 LSTs) who
      received a multidetector CT scan using contrast media immediately after total
      colonoscopy at the National Cancer Center Hospital in Tokyo, Japan, between
      December 2005 and August 2010. The results of the total colonoscopy were known at
      the time of the CTC procedure and reading. Of the 161 LSTs detected on
      colonoscopy, 138 were observed and matched by CTC (86%). Of the 91 granular type
      LSTs (LST-Gs), 88 (97%) were observed and matched, while of the 70 non-granular
      type LSTs (LST-NGs), 50 (71%) were observed and matched by CTC (p<0.0001). CTC
      enabled observation of 73% (22/30) of 20-29 mm, 83% (35/42) of 30-39 mm, 88%
      (49/56) of 40-59 mm, and 97% (32/33) of >=60 mm tumors. The rate of observed LSTs
      by CTC was 86% (97% of LST-G, 71% of LST-NG) of the LSTs found during total
      colonoscopy.

PMID- 24300096
TI  - In vitro corrosion and cytocompatibility of ZK60 magnesium alloy coated with
      hydroxyapatite by a simple chemical conversion process for orthopedic
      applications.
AB  - Magnesium and its alloys--a new class of degradable metallic biomaterials-are
      being increasingly investigated as a promising alternative for medical implant
      and device applications due to their advantageous mechanical and biological
      properties. However, the high corrosion rate in physiological environments
      prevents the clinical application of Mg-based materials. Therefore, the objective
      of this study was to develop a hydroxyapatite (HA) coating on ZK60 magnesium
      alloy substrates to mediate the rapid degradation of Mg while improving its
      cytocompatibility for orthopedic applications. A simple chemical conversion
      process was applied to prepare HA coating on ZK60 magnesium alloy. Surface
      morphology, elemental compositions, and crystal structures were characterized
      using scanning electron microscopy, energy dispersive spectroscopy, and X-ray
      diffraction, respectively. The corrosion properties of samples were investigated
      by immersion test and electrochemical test. Murine fibroblast L-929 cells were
      harvested and cultured with coated and non-coated ZK60 samples to determine
      cytocompatibility. The degradation results suggested that the HA coatings
      decreased the degradation of ZK60 alloy. No significant deterioration in
      compression strength was observed for all the uncoated and coated samples after 2
      and 4 weeks' immersion in simulated body fluid (SBF). Cytotoxicity test indicated
      that the coatings, especially HA coating, improved cytocompatibility of ZK60
      alloy for L929 cells.

PMID- 24300098
TI  - Sustained release of prindopril erbumine from its chitosan-coated magnetic
      nanoparticles for biomedical applications.
AB  - The preparation of magnetic nanoparticles coated with chitosan-prindopril
      erbumine was accomplished and confirmed by X-ray diffraction, TEM, magnetic
      measurements, thermal analysis and infrared spectroscopic studies. X-ray
      diffraction and TEM results demonstrated that the magnetic nanoparticles were
      pure iron oxide phase, having a spherical shape with a mean diameter of 6 nm,
      compared to 15 nm after coating with chitosan-prindopril erbumine (FCPE). Fourier
      transform infrared spectroscopy study shows that the coating of iron oxide
      nanoparticles takes place due to the presence of some bands that were emerging
      after the coating process, which belong to the prindopril erbumine (PE). The
      thermal stability of the PE in an FCPE nanocomposite was remarkably enhanced. The
      release study showed that around 89% of PE could be released within about 93
      hours by a phosphate buffer solution at pH 7.4, which was found to be of
      sustained manner governed by first order kinetic. Compared to the control
      (untreated), cell viability study in 3T3 cells at 72 h post exposure to both the
      nanoparticles and the pure drug was found to be sustained above 80% using
      different doses. 

PMID- 24300099
TI  - A role of VIPP1 as a dynamic structure within thylakoid centers as sites of
      photosystem biogenesis?
AB  - The vesicle inducing protein in plastids (VIPP1) is an essential protein for the
      biogenesis of thylakoids in modern cyanobacteria, algae, and plants. Although its
      exact function is still not clear, recent work has provided important hints to
      its mode of action. We believe that these data are consistent with a structural
      role of VIPP1 within thylakoid centers, which are considered as sites from which
      thylakoid membranes emerge and at which the biogenesis at least of photosystem II
      is thought to occur. Here we present a model that may serve as starting point for
      future research. 

PMID- 24300100
TI  - Enablers and barriers to large-scale uptake of improved solid fuel stoves: a
      systematic review.
AB  - BACKGROUND: Globally, 2.8 billion people rely on household solid fuels. Reducing
      the resulting adverse health, environmental, and development consequences will
      involve transitioning through a mix of clean fuels and improved solid fuel stoves
      (IS) of demonstrable effectiveness. To date, achieving uptake of IS has presented
      significant challenges. OBJECTIVES: We performed a systematic review of factors
      that enable or limit large-scale uptake of IS in low- and middle-income
      countries. METHODS: We conducted systematic searches through multidisciplinary
      databases, specialist websites, and consulting experts. The review drew on
      qualitative, quantitative, and case studies and used standardized methods for
      screening, data extraction, critical appraisal, and synthesis. We summarized our
      findings as "factors" relating to one of seven domains-fuel and technology
      characteristics; household and setting characteristics; knowledge and
      perceptions; finance, tax, and subsidy aspects; market development; regulation,
      legislation, and standards; programmatic and policy mechanisms-and also recorded
      issues that impacted equity. RESULTS: We identified 31 factors influencing uptake
      from 57 studies conducted in Asia, Africa, and Latin America. All domains matter.
      Although factors such as offering technologies that meet household needs and save
      fuel, user training and support, effective financing, and facilitative government
      action appear to be critical, none guarantee success: All factors can be
      influential, depending on context. The nature of available evidence did not
      permit further prioritization. CONCLUSIONS: Achieving adoption and sustained use
      of IS at a large scale requires that all factors, spanning household/community
      and program/societal levels, be assessed and supported by policy. We propose a
      planning tool that would aid this process and suggest further research to
      incorporate an evaluation of effectiveness.

PMID- 24300101
TI  - Budding yeast protein extraction and purification for the study of function,
      interactions, and post-translational modifications.
AB  - Homogenization by bead beating is a fast and efficient way to release DNA, RNA,
      proteins, and metabolites from budding yeast cells, which are notoriously hard to
      disrupt. Here we describe the use of a bead mill homogenizer for the extraction
      of proteins into buffers optimized to maintain the functions, interactions and
      post-translational modifications of proteins. Logarithmically growing cells
      expressing the protein of interest are grown in a liquid growth media of choice.
      The growth media may be supplemented with reagents to induce protein expression
      from inducible promoters (e.g. galactose), synchronize cell cycle stage (e.g.
      nocodazole), or inhibit proteasome function (e.g. MG132). Cells are then pelleted
      and resuspended in a suitable buffer containing protease and/or phosphatase
      inhibitors and are either processed immediately or frozen in liquid nitrogen for
      later use. Homogenization is accomplished by six cycles of 20 sec bead-beating
      (5.5 m/sec), each followed by one minute incubation on ice. The resulting
      homogenate is cleared by centrifugation and small particulates can be removed by
      filtration. The resulting cleared whole cell extract (WCE) is precipitated using
      20% TCA for direct analysis of total proteins by SDS-PAGE followed by Western
      blotting. Extracts are also suitable for affinity purification of specific
      proteins, the detection of post-translational modifications, or the analysis of
      co-purifying proteins. As is the case for most protein purification protocols,
      some enzymes and proteins may require unique conditions or buffer compositions
      for their purification and others may be unstable or insoluble under the
      conditions stated. In the latter case, the protocol presented may provide a
      useful starting point to empirically determine the best bead-beating strategy for
      protein extraction and purification. We show the extraction and purification of
      an epitope-tagged SUMO E3 ligase, Siz1, a cell cycle regulated protein that
      becomes both sumoylated and phosphorylated, as well as a SUMO-targeted ubiquitin
      ligase subunit, Slx5.

PMID- 24300103
TI  - Impact of the Iranian hospital grading system on hospitals' adherence to audited
      standards: an examination of possible mechanisms.
AB  - INTRODUCTION: All Iranian hospitals have been subject to a grading system which
      determines the payments they can charge. We examined all possible pathways
      through which the grading system could influence hospitals' adherence to audited
      standards. METHODS: Using a mixed methods study we examined five stakeholder
      groups: hospital staff, patients, general practitioners, health insurance
      organisations and surveyor organisations. Data were collected via semi-structured
      interviews, a questionnaire survey, observation and documentary analysis.
      FINDINGS: Patients and general practitioners were generally unaware of the
      hospital grading. Hospital staff and insurance organisations were informed, but
      this was not found to influence the hospital staff's choice of where to work nor
      the insurance organisations contracting behaviour. The grading system was
      criticised for the performance standards' validity and the validity of hospitals'
      awarded results. Hospitals responded to financial and reputational incentives for
      achieving better grades, although gaming and misrepresentation was also reported.
      CONCLUSION: Pay-for-performance was the main influential factor in shaping
      hospitals' adherence to audit standards. Other potential mechanisms for
      influencing hospital behaviour, the selection mechanism and intrinsic motives,
      were not found to be sufficient to affect hospital behaviour.

PMID- 24300102
TI  - Inter-subunit interactions between glutamate-like receptors in Arabidopsis.
AB  - The plant Glutamate-Like Receptors (GLRs) are homologs of animal ionotropic
      glutamate receptors (iGluRs), and are hypothesized to be potential amino acid
      sensors in plants. Genetic studies of proteins from this family implicate
      individual GLRs in a diversity of physiological roles in plants. Recently, amino
      acid gated channel activities have been proven for a few plant GLRs, suggesting
      that at least some of the functional mechanisms are conserved between plant GLRs
      and animal iGluRs. Animal iGluRs generally form heterotetramers, and the ligand
      binding specificity and channel functionality is determined by interaction
      between the subunits. In order to investigate whether plant GLRs interact with
      each other, a modified yeast-2-hybrid system (mbSUS) approach was taken on 15 of
      the 20 Arabidopsis GLRs to identify potential interaction partners. Using this
      approach, we have successfully identified GLR subunits that are capable of
      interacting with multiple other GLRs. Unlike iGluRs, sequence similarity between
      the subunit was not correlated with the likelihood of interaction among 2 given
      subunits. Interactions between selected GLRs (GLR1.1, 2.9, 3.2, and 3.4) were
      further tested in another heterologous expression system, mammalian HEK293 cells,
      using Forster resonance energy transfer (FRET). Two separate approaches
      (sensitized FRET and acceptor photobleaching) indicated that GLRs 1.1 and 3.4 are
      capable of forming homomers, whereas other combinations did not result in
      detectable FRET between the subunits.

PMID- 24300104
TI  - The Influence of Age-Related Differences in Prior Knowledge and Attentional
      Refreshing Opportunities on Episodic Memory.
AB  - OBJECTIVES: The assumption that working memory (WM) is embedded within long-term
      memory suggests that the effectiveness of switching information between activated
      states in WM (i.e., attentional refreshing) may depend on whether that
      information is semantically relevant. Given that older adults often have greater
      general knowledge than younger adults, age-related deficits in episodic memory
      (EM) could be ameliorated by studying information that has existing semantic
      representations compared with unknown information. METHOD: Younger and older
      adults completed a modified operation span task that varied the number of
      refreshing opportunities. The memoranda used were equally known to younger and
      older adults (neutral words; e.g., father), better known to older adults than
      younger adults (dated words; e.g., mirth), or unknown to both groups (unknown
      words; e.g., cobot). RESULTS: Results for immediate and delayed recall indicated
      an age-related improvement for dated memoranda and no age difference for unknown
      memoranda. Furthermore, refreshing opportunities predicted delayed recall of
      neutral memoranda more strongly for younger adults than older adults, whereas
      older adults' recall advantage for dated memoranda was explained by their prior
      knowledge and not refreshing opportunities. DISCUSSION: The results suggest that
      older adults' EM deficits could potentially be ameliorated by incorporating their
      superior knowledge to supplement relatively ineffective attentional refreshing in
      WM.

PMID- 24300105
TI  - Predictive value of echocardiography-derived arterial compliance for increased
      arterial stiffness in hypertensive patients.
AB  - OBJECTIVE: Increased arterial stiffness is a predictor of cardiovascular events.
      The cardio-ankle vascular index (CAVI) is a measure of arterial stiffness. The
      stroke volume (SV) to pulse pressure (PP) ratio is an estimate of arterial
      compliance (AC). The main purpose of this study was to investigate the
      association between echocardiography-derived AC and arterial stiffness. METHODS:
      One hundred and forty asymptomatic hypertensive patients were enrolled
      consecutively. AC was calculated as SV/PP and adjusted to body surface area to
      calculate the SV/PP index (SV/PPi). Arterial stiffness was assessed by a VaSera
      1000 CAVI instrument. RESULTS: There was statistically significant negative
      correlation between SV/PPi and CAVI (r=-0.402; P<0.001). Multivariate binary
      logistic regression analysis demonstrated SV/PPi as an independent predictor of
      increased CAVI (CAVI>=9) (95% confidence interval: 0.001-0.147; P<0.001). There
      were lower SV/PPi values in abnormal CAVI groups (CAVI>=9) than normal and
      borderline CAVI (CAVI<9) (0.68+/-0.23 vs. 0.93+/-0.27; P<0.001). Analysis using
      the receiver operating characteristic curve has demonstrated that SV/PPi of 0.61
      ml/m/mmHg constitutes the cut-off value for the presence of abnormal CAVI with
      89% sensitivity and 53% specificity (area under the curve: 0.771, 95% confidence
      interval 0.674-0.868). CONCLUSION: Assessment of AC during echocardiography
      examination may provide predictive information of increased arterial stiffness in
      asymptomatic hypertensive patients.

PMID- 24300106
TI  - Calcium phosphate transfection of primary hippocampal neurons.
AB  - Calcium phosphate precipitation is a convenient and economical method for
      transfection of cultured cells. With optimization, it is possible to use this
      method on hard-to-transfect cells like primary neurons. Here we describe our
      detailed protocol for calcium phosphate transfection of hippocampal neurons
      cocultured with astroglial cells. 

PMID- 24300107
TI  - EASY: a simple tool for simultaneously removing background, deadtime and acoustic
      ringing in quantitative NMR spectroscopy--part I: basic principle and
      applications.
AB  - Elimination of Artifacts in NMR SpectroscopY (EASY) is a simple but very
      effective tool to remove simultaneously any real NMR probe background signal, any
      spectral distortions due to deadtime ringdown effects and -specifically- severe
      acoustic ringing artifacts in NMR spectra of low-gamma nuclei. EASY enables and
      maintains quantitative NMR (qNMR) as only a single pulse (preferably 90 degrees )
      is used for data acquisition. After the acquisition of the first scan (it
      contains the wanted NMR signal and the background/deadtime/ringing artifacts) the
      same experiment is repeated immediately afterwards before the T1 waiting delay.
      This second scan contains only the background/deadtime/ringing parts. Hence, the
      simple difference of both yields clean NMR line shapes free of artefacts. In this
      Part I various examples for complete (1)H, (11)B, (13)C, (19)F probe background
      removal due to construction parts of the NMR probes are presented. Furthermore,
      (25)Mg EASY of Mg(OH)2 is presented and this example shows how extremely strong
      acoustic ringing can be suppressed (more than a factor of 200) such that phase
      and baseline correction for spectra acquired with a single pulse is no longer a
      problem. EASY is also a step towards deadtime-free data acquisition as these
      effects are also canceled completely. EASY can be combined with any other NMR
      experiment, including 2D NMR, if baseline distortions are a big problem. 

PMID- 24300109
TI  - Primary cultures of rat cortical microglia treated with nicotine increases in the
      expression of excitatory amino acid transporter 1 (GLAST) via the activation of
      the alpha7 nicotinic acetylcholine receptor.
AB  - Although the clearance of glutamate from the synapse under physiological
      conditions is performed by astrocytic glutamate transporters, their expression
      might be diminished under pathological conditions. Microglia glutamate
      transporters, however, might serve as a back-up system when astrocytic glutamate
      uptake is impaired, and could have a prominent neuroprotective function under
      pathological conditions. In the current study, the effect of nicotine, well known
      as a neuroprotective molecule, on the function of glutamate transporters in
      cultured rat cortical microglia was examined. Reverse transcription polymerase
      chain reaction and pharmacological approaches demonstrated that,
      glutamate/aspartate transporter (GLAST), not glutamate transporter 1 (GLT-1), is
      the major functional glutamate transporter in cultured cortical microglia.
      Furthermore, the alpha7 subunit was demonstrated to be the key subunit comprising
      nicotinic acetylcholine (nACh) receptors in these cells. Treatment of cortical
      microglia with nicotine led to a significant increase of GLAST mRNA expression
      and (14)C-glutamate uptake in a concentration- and time-dependent manner, which
      were markedly inhibited by pretreatment with methyllycaconitine, a selective
      alpha7 nACh receptor antagonist. The nicotine-induced expression of GLAST mRNA
      and protein is mediated through an inositol trisphosphate (IP3) and
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) depend intracellular
      pathway, since pretreatment with either xestospongin C, an IP3 receptor
      antagonist, or KN-93, a CaMKII inhibitor, blocked GLAST expression. Together,
      these findings indicate that activation of nACh receptors, specifically those
      expressing the alpha7 subunit, on cortical microglia could be a key mechanism of
      the neuroprotective effect of nACh receptor ligands such as nicotine. 

PMID- 24300110
TI  - Comparison of software packages for detecting differential expression in RNA-seq
      studies.
AB  - RNA-sequencing (RNA-seq) has rapidly become a popular tool to characterize
      transcriptomes. A fundamental research problem in many RNA-seq studies is the
      identification of reliable molecular markers that show differential expression
      between distinct sample groups. Together with the growing popularity of RNA-seq,
      a number of data analysis methods and pipelines have already been developed for
      this task. Currently, however, there is no clear consensus about the best
      practices yet, which makes the choice of an appropriate method a daunting task
      especially for a basic user without a strong statistical or computational
      background. To assist the choice, we perform here a systematic comparison of
      eight widely used software packages and pipelines for detecting differential
      expression between sample groups in a practical research setting and provide
      general guidelines for choosing a robust pipeline. In general, our results
      demonstrate how the data analysis tool utilized can markedly affect the outcome
      of the data analysis, highlighting the importance of this choice. 

PMID- 24300111
TI  - High-throughput DNA sequence data compression.
AB  - The exponential growth of high-throughput DNA sequence data has posed great
      challenges to genomic data storage, retrieval and transmission. Compression is a
      critical tool to address these challenges, where many methods have been developed
      to reduce the storage size of the genomes and sequencing data (reads, quality
      scores and metadata). However, genomic data are being generated faster than they
      could be meaningfully analyzed, leaving a large scope for developing novel
      compression algorithms that could directly facilitate data analysis beyond data
      transfer and storage. In this article, we categorize and provide a comprehensive
      review of the existing compression methods specialized for genomic data and
      present experimental results on compression ratio, memory usage, time for
      compression and decompression. We further present the remaining challenges and
      potential directions for future research. 

PMID- 24300112
TI  - Searching for repetitions in biological networks: methods, resources and tools.
AB  - We present here a compact overview of the data, models and methods proposed for
      the analysis of biological networks based on the search for significant
      repetitions. In particular, we concentrate on three problems widely studied in
      the literature: 'network alignment', 'network querying' and 'network motif
      extraction'. We provide (i) details of the experimental techniques used to obtain
      the main types of interaction data, (ii) descriptions of the models and
      approaches introduced to solve such problems and (iii) pointers to both the
      available databases and software tools. The intent is to lay out a useful roadmap
      for identifying suitable strategies to analyse cellular data, possibly based on
      the joint use of different interaction data types or analysis techniques. 

PMID- 24300108
TI  - Ethanol induced acetylation of histone at G9a exon1 and G9a-mediated histone H3
      dimethylation leads to neurodegeneration in neonatal mice.
AB  - The transient exposure of immature rodents to ethanol during postnatal day 7
      (P7), comparable to a time point within the third trimester of human pregnancy,
      induces neurodegeneration. However, the molecular mechanisms underlying the
      deleterious effects of ethanol on the developing brain are poorly understood. In
      our previous study, we showed that a high dose administration of ethanol at P7
      enhances G9a and leads to caspase-3-mediated degradation of dimethylated H3 on
      lysine 9 (H3K9me2). In this study, we investigated the potential role of
      epigenetic changes at G9a exon1, G9a-mediated H3 dimethylation on
      neurodegeneration and G9a-associated proteins in the P7 brain following exposure
      to a low dose of ethanol. We found that a low dose of ethanol induces mild
      neurodegeneration in P7 mice, enhances specific acetylation of H3 on lysine 14
      (H3K14ace) at G9a exon1, G9a protein levels, augments the dimethylation of H3K9
      and H3 lysine 27 (H3K27me2). However, neither dimethylated H3K9 nor K27 underwent
      degradation. Pharmacological inhibition of G9a activity prior to ethanol
      treatment prevented H3 dimethylation and neurodegeneration. Further, our
      immunoprecipitation data suggest that G9a directly associates with DNA
      methyltransferase (DNMT3A) and methyl-CpG-binding protein 2 (MeCP2). In addition,
      DNMT3A and MeCP2 protein levels were enhanced by a low dose of ethanol that was
      shown to induce mild neurodegeneration. Collectively, these epigenetic
      alterations lead to association of G9a, DNMT3A and MeCP2 to form a larger
      repressive complex and have a significant role in low-dose ethanol-induced
      neurodegeneration in the developing brain. 

PMID- 24300113
TI  - Effect of crowding by Dextrans in enzymatic reactions.
AB  - The interior of the living cell is highly concentrated and structured with
      molecules that have different shapes and sizes. Almost all experimental
      biochemical data have been obtained working in dilute solutions, situations which
      do not reflect the in vivo conditions. The consequences of such crowding upon
      enzymatic reactions remain unclear. In this paper, we have studied and compared
      the initial velocity of the hydrolysis of N-succinyl-L-phenyl-Ala-p-nitroanilide
      catalyzed by alpha-chymotrypsin, the oxidation of ABTS by H2O2 catalyzed by HRP
      and the oxidation of NADH in presence of pyruvate catalyzed by LDH. These
      reactions were chosen as model enzymatic processes occurring in different in
      vitro crowded media. The systems crowding has been built by introducing Dextran
      of several concentrations and sizes. Our results indicate that the volume
      occupied by the crowding agent, but not its size, plays an important role on the
      initial velocity of reactions involving tiny enzymes. However, the enzyme size is
      another important factor influencing the velocity of the reactions of large
      enzymes occurring in Dextran crowded media. In this situation, the reaction
      initial velocity depends on both occupied volume and dimension of the crowding
      agent that is present in the reaction media.

PMID- 24300114
TI  - Tibial nerve transection - a standardized model for denervation-induced skeletal
      muscle atrophy in mice.
AB  - The tibial nerve transection model is a well-tolerated, validated, and
      reproducible model of denervation-induced skeletal muscle atrophy in rodents.
      Although originally developed and used extensively in the rat due to its larger
      size, the tibial nerve in mice is big enough that it can be easily manipulated
      with either crush or transection, leaving the peroneal and sural nerve branches
      of the sciatic nerve intact and thereby preserving their target muscles. Thus,
      this model offers the advantages of inducing less morbidity and impediment of
      ambulation than the sciatic nerve transection model and also allows investigators
      to study the physiologic, cellular and molecular biologic mechanisms regulating
      the process of muscle atrophy in genetically engineered mice. The tibial nerve
      supplies the gastrocnemius, soleus and plantaris muscles, so its transection
      permits the study of denervated skeletal muscle composed of fast twitch type II
      fibers and/or slow twitch type I fibers. Here we demonstrate the tibial nerve
      transection model in the C57Black6 mouse. We assess the atrophy of the
      gastrocnemius muscle, as a representative muscle, at 1, 2, and 4 weeks post
      denervation by measuring muscle weights and fiber type specific cross-sectional
      area on paraffin-embedded histologic sections immunostained for fast twitch
      myosin. 

PMID- 24300115
TI  - In utero measurement of heart rate in mouse by noninvasive M-mode
      echocardiography.
AB  - Congenital heart disease (CHD) is the most frequent noninfectious cause of death
      at birth. The incidence of CHD ranges from 4 to 50/1,000 births (Disease and
      injury regional estimates, World Health Organization, 2004). Surgeries that often
      compromise the quality of life are required to correct heart defects, reminding
      us of the importance of finding the causes of CHD. Mutant mouse models and live
      imaging technology have become essential tools to study the etiology of this
      disease. Although advanced methods allow live imaging of abnormal hearts in
      embryos, the physiological and hemodynamic states of the latter are often
      compromised due to surgical and/or lengthy procedures. Noninvasive ultrasound
      imaging, however, can be used without surgically exposing the embryos, thereby
      maintaining their physiology. Herein, we use simple M-mode ultrasound to assess
      heart rates of embryos at E18.5 in utero. The detection of abnormal heart rates
      is indeed a good indicator of dysfunction of the heart and thus constitutes a
      first step in the identification of developmental defects that may lead to heart
      failure. 

PMID- 24300116
TI  - Default mode network: the seat of literary creativity?
AB  - Literacy implies convergence, with heard and read narratives directed from
      separate sensory pathways towards common linguistic and semantic brain systems -
      very 'bottom-up'. But we also actively infer, relate, remember, attend and, above
      all, imagine - very 'top-down'. We comment on an interesting investigation of the
      listening and reading brain. 

PMID- 24300117
TI  - Mild bilateral and unilateral hearing loss in childhood: a 20-year view of
      hearing characteristics, and audiologic practices before and after newborn
      hearing screening.
AB  - OBJECTIVES: There is some evidence that the presence of even mild degrees of
      hearing loss and unilateral loss in early childhood can negatively affect typical
      development. Consequently, the identification of all children with permanent
      hearing loss including those with milder degrees of hearing loss is currently
      targeted through some newborn hearing screening initiatives. The objectives of
      this study were to document the proportion of children identified with mild
      bilateral or unilateral hearing loss (MBUHL) before and after the implementation
      of a universal newborn hearing screening program (UNHS). A second objective was
      to examine the clinical characteristics and audiologic management of this
      population of children. DESIGN: This population-based study involved an analysis
      of data on children with hearing loss; these data had been collected
      prospectively over a 20-year period from 1990 to 2010 in a publicly funded
      pediatric teaching hospital in Canada, which provided diagnostic audiology
      services for all children in the region. The proportion of all children with
      hearing loss identified with MBUHL before and after implementation of UNHS and
      their clinical profiles were documented. Data related to amplification use were
      also retrospectively extracted from detailed medical chart reviews to investigate
      clinical recommendations regarding amplification and subsequent use of hearing
      devices. Factors affecting amplification decisions and amplification use were
      examined. RESULTS: A total of 381 of 823 children (46.3%) aged 0 to 18 years who
      were identified with permanent nonacquired hearing loss presented with MBUHL. The
      proportions identified were similar in the pre- and post-UNHS periods (p =
      0.207). Before UNHS children were identified at a median age of 5.0 years
      (interquartile range: 3.6 to 7.0) compared with a median of 0.8 years,
      (interquartile range: 0.3 to 2.3) post-UNHS. Progression of hearing loss was
      documented for 22% of all children, and for the group identified since UNHS,
      32.4% experienced deterioration in hearing thresholds. Although 87.2 % of
      children received recommendations for amplification, more than 50% experienced
      considerable delay from identification to amplification. Age at identification
      and severity of hearing loss in the better ear were associated with amplification
      decisions for bilateral but not unilateral loss. CONCLUSIONS: MBUHL constitutes
      almost half of childhood hearing loss. UNHS has lowered age of confirmation of
      MBUHL by 4 to 5 years. Delay to amplification suggests uncertainty of the benefit
      of intervening early for these losses. Further research is required to determine
      the effects of early-identified MBUHL on children's development and to document
      the benefits of early amplification.

PMID- 24300118
TI  - Synthesis and binding ability of molecular probes based on a phenanthroline
      derivative: theory and experiment.
AB  - A fluorescent and colorimetric molecular probe containing phenol groups has been
      designed and synthesized. The anion binding ability was evaluated for biolgically
      important anions (F-, Cl-, Br-, I-, AcO- and H2PO4-) by theoretical
      investigation, UV-Vis and fluorescence spectroscopy and 1H-NMR titration
      experiments. Results indicated the probe showed strong binding ability for H2PO4-
      without the interference of other anions tested and the interaction process was
      accompanied by color changes. Theoretical investigation analysis revealed that
      intramolecular hydrogen bonds existed in the structure of the probe and the roles
      of molecular frontier orbitals in molecular interplay were determined. 

PMID- 24300119
TI  - Quality evaluation of Panax ginseng roots using a rapid resolution LC-QTOF/MS
      based metabolomics approach.
AB  - Korean ginseng (Panax ginseng C.A. Meyer) contains several types of ginsenosides,
      which are considered the major active medicinal components of ginseng. The types
      and quantities of ginsenosides found in ginseng may differ, depending on the
      location of cultivation, making it necessary to establish a reliable method for
      distinguishing cultivation locations of ginseng roots. P. ginseng roots produced
      in different regions of Korea, China, and Japan have been unintentionally
      confused in herbal markets owing to their complicated plant sources. PCA and PLS
      DA using RRLC-QTOF/MS data was able to differentiate between ginsengs cultivated
      in Korea, China, and Japan. The chemical markers accountable for such variations
      were identified through a PCA loadings plot, tentatively identified by RRLC
      QTOF/MS and partially verified by available reference standards. The
      classification result can be used to identify P. ginseng origin. 

PMID- 24300120
TI  - Immunomodulatory effects of Hedysarum polybotrys extract in mice macrophages,
      splenocytes and leucopenia.
AB  - Astragali Radix (Huang-Qi) is a popular herbal medicine commonly used as a
      constituent in tonic herbal preparations. Hedysarum polybotrys Handel-Mazzetti is
      one species used of Astragali Radix. In this study, the immunomodulatory
      properties of H. polybotrys were explored by LPS-activated and SNP-treated RAW
      264.7 cells and splenocytes and, daunoblastina-induced leucopenia BALB/c mice.
      Formononetin was used as the bioactive marker to monitor the quality of the H.
      polybotrys extracts. H. polybotrys was extracted with hot-water and methanol, and
      MeOH extract partitioned with H2O (M-H) and ethyl acetate (M-EA) to yield four
      different fractions. M-EA had the highest formononetin and total proanthocyanidin
      content and showed stronger inhibitory effects on the production and expression
      of NO, PGE2, iNOS and COX-2 in LPS-activated RAW 264.7 cells and splenocytes than
      the other fractions. In addition, M-EA significantly stimulated the proliferation
      of LPS-activated RAW 264.7 cells and splenocytes, enhanced NO radicals scavenging
      and attenuated NO-induced cytotoxicity.  Furthermore, M-EA also significantly
      increased the rate of recovery of white blood cells level in daunoblastina
      induced leucopenia mice. These evidences suggest that this traditional Qi
      tonifying herb has potential effects in clinical conditions when immune-enhancing
      and anti-inflammatory effect is desired. 

PMID- 24300121
TI  - Design, synthesis, biological activities and 3D-QSAR of new N,N'-diacylhydrazines
      containing 2,4-dichlorophenoxy moieties.
AB  - A series of new N,N'-diacylhydrazine derivatives were designed and synthesized.
      Their structures were verified by 1H-NMR, MS and elemental analysis. The
      herbicidal activities and plant growth regulating activity of these N,N'
      diacylhydrazines were evaluated. The herbicidal activity results showed that most
      of these N,N'-diacyl-hydrazines showed excellent in vivo activities against
      Echinochloa crus-galli, Digitaria sanguinalis, Brassica napus, Amaranthus
      retroflerus. Most of them exhibited higher herbicidal activities against
      dicotyledonous weeds than monocotyledonous weeds. To further investigate the
      structure-activity relationship, comparative molecular field analysis (CoMFA) was
      performed on the basis of herbicidal activity data. Both the steric and
      electronic field distributions of CoMFA are in good agreement in this work. 

PMID- 24300122
TI  - Impact of knee modeling approach on indicators and classification of anterior
      cruciate ligament injury risk.
AB  - INTRODUCTION: The aim of this study was to determine whether using a direct
      kinematic (DK) or inverse kinematic (IK) modeling approach could influence the
      estimation of knee joint kinematics, kinetics, and ACL injury risk classification
      during unanticipated side cutting. METHODS: The three-dimensional motion and
      force data of 34 amateur Australian rules footballers conducting unanticipated
      side-cutting maneuvers were collected. The model used during the DK modeling
      approach was an eight-segment lower body model with the hip, knee, and ankle free
      to move in six degrees of freedom. During the IK modeling approach, the same
      eight-segment model was used; however, translational constraints were imposed on
      the hip, knee, and ankle joints. The similarity between kinematic and kinetic
      waveforms was evaluated using the root mean square difference (RMSD) and the one
      dimensional statistical parametric mapping (SPM1D). The classification of an
      athlete's ACL injury risk was determined by correlating their peak knee moments
      with a predefined injury risk threshold. RESULTS: The greatest RMSD occurred in
      the frontal plane joint angles (RMSD = 10.86 degrees ) and moments (RMSD = 0.67
      +/- 0.18 N.m.kg(-1)), which were also shown to be significantly different
      throughout the stance phase in the SPM1D analysis. Both DK and IK modeling
      approaches classified the same athletes as being at risk of ACL injury.
      CONCLUSIONS: The choice of a DK or an IK modeling approach affected frontal plane
      estimates of knee joint angles and peak knee moments during the weight acceptance
      phase of unanticipated side cutting. However, both modeling approaches were
      similar in their classification of an athlete's ACL injury risk.

PMID- 24300123
TI  - Deception studies manipulating centrally acting performance modifiers: a review.
AB  - Athletes anticipatorily set and continuously adjust pacing strategies before and
      during events to produce optimal performance. Self-regulation ensures maximal
      effort is exerted in correspondence with the end point of exercise, while
      preventing physiological changes that are detrimental and disruptive to
      homeostatic control. The integration of feedforward and feedback information,
      together with the proposed brain's performance modifiers is said to be
      fundamental to this anticipatory and continuous regulation of exercise. The
      manipulation of central, regulatory internal and external stimuli has been a key
      focus within deception research, attempting to influence the self-regulation of
      exercise and induce improvements in performance. Methods of manipulating
      performance modifiers such as unknown task end point, deceived duration or
      intensity feedback, self-belief, or previous experience create a challenge within
      research, as although they contextualize theoretical propositions, there are few
      ecological and practical approaches which integrate theory with practice. In
      addition, the different methods and measures demonstrated in manipulation studies
      have produced inconsistent results. This review examines and critically evaluates
      the current methods of how specific centrally controlled performance modifiers
      have been manipulated, within previous deception studies. From the 31 studies
      reviewed, 10 reported positive effects on performance, encouraging future
      investigations to explore the mechanisms responsible for influencing pacing and
      consequently how deceptive approaches can further facilitate performance. The
      review acts to discuss the use of expectation manipulation not only to examine
      which methods of deception are successful in facilitating performance but also to
      understand further the key components used in the regulation of exercise and
      performance. 

PMID- 24300124
TI  - Rearfoot and midfoot or forefoot impacts in habitually shod runners.
AB  - PURPOSE: Shear loading rates (LR) have not been investigated in runners with a
      mid- or forefoot strike (FFS) versus rearfoot strike (RFS). The purpose of this
      study was to compare three-dimensional ground reaction forces (GRF) and LR during
      impact in habitual rearfoot strikers (hRF) and habitual forefoot strikers (hFF)
      strikers. METHODS: Thirty competitive runners performed 10 overground running
      trials with both foot strike styles. Peak three-dimensional and resultant GRF and
      instantaneous LR during impact were compared. RESULTS: Vertical LR significantly
      decreased for hRF using an FFS (RFS = 148 +/- 36 body weight [BW].s(-1), FFS = 98
      +/- 31 BW.s(-1)) but was similar for hFF running with either foot strike (FFS =
      136 +/- 35 BW.s(-1), RFS = 135 +/- 28 BW.s(-1)). Posterior impact forces were
      present during FFS but not during RFS, and posterior LR was significantly greater
      for both groups during FFS (-58 +/- 17 vs -19 +/- 6 BW.s(-1)). Medial impact
      forces were also present during FFS but not during RFS, and medial LR was
      significantly larger for both groups during FFS (-21 +/- 7 vs -6 +/- 6 BW.s(-1)).
      Interestingly, hFF had greater impact peaks and LR in all directions compared
      with hRF during FFS. This may be explained by hFF using a smaller strike index
      (hFF = 62% +/- 9%, hRF = 67% +/- 9%; P = 0.02), which was significantly inversely
      related to vertical LR and impact peak. CONCLUSIONS: Peak resultant and vertical
      LR are not ubiquitously lower when using a shod FFS versus RFS despite an absence
      of resultant and vertical impact peaks. Furthermore, there were impact peaks in
      the posterior and medial directions, leading also to greater LR in these
      directions during FFS. Therefore, transitioning from RFS to FFS in traditional
      running shoes may not offer long-term protection against impact-related running
      injuries because hFF running with an FFS demonstrated many GRF and LR similar to
      or greater than RFS.

PMID- 24300125
TI  - Examining variations of resting metabolic rate of adults: a public health
      perspective.
AB  - PURPOSE: There has not been a recent comprehensive effort to examine existing
      studies on the resting metabolic rate (RMR) of adults to identify the effect of
      common population demographic and anthropometric characteristics. Thus, we
      reviewed the literature on RMR (kcal.kg(-1).h(-1)) to determine the relationship
      of age, sex, and obesity status to RMR as compared with the commonly accepted
      value for the metabolic equivalent (MET; e.g., 1.0 kcal.kg(-1).h(-1)). METHODS:
      Using several databases, scientific articles published from 1980 to 2011 were
      identified that measured RMR, and from those, others dating back to 1920 were
      identified. One hundred and ninety-seven studies were identified, resulting in
      397 publication estimates of RMR that could represent a population subgroup.
      Inverse variance weighting technique was applied to compute means and 95%
      confidence intervals (CI). RESULTS: The mean value for RMR was 0.863 kcal.kg(
      1).h(-1) (95% CI = 0.852-0.874), higher for men than women, decreasing with
      increasing age, and less in overweight than normal weight adults. Regardless of
      sex, adults with BMI >= 30 kg.m(-2) had the lowest RMR (<0.741 kcal.kg(-1).h(
      1)). CONCLUSIONS: No single value for RMR is appropriate for all adults. Adhering
      to the nearly universally accepted MET convention may lead to the overestimation
      of the RMR of approximately 10% for men and almost 15% for women and be as high
      as 20%-30% for some demographic and anthropometric combinations. These large
      errors raise questions about the longstanding adherence to the conventional MET
      value for RMR. Failure to recognize this discrepancy may result in important
      miscalculations of energy expended from interventions using physical activity for
      diabetes and other chronic disease prevention efforts.

PMID- 24300126
TI  - Thermoregulatory responses are attenuated after fructose but not glucose intake.
AB  - PURPOSE: We examined whether plasma hyperosmolality induced by oral
      monosaccharide intake attenuated thermoregulatory responses and whether the
      responses were different between fructose and glucose. METHODS: Ten healthy young
      subjects performed three trials in a sitting position in an artificial climate
      chamber (ambient temperature, 28 degrees C; relative humidity, 40%). After
      resting for 10 min, the subjects drank 300 mL of water alone (control), or 300 mL
      of water supplemented with 75 g fructose or 75 g glucose. Twenty minutes later,
      they were heated passively by immersing the lower legs in water at 42 degrees C
      for 60 min. Plasma osmolality (Posm), sodium ([Na+]p) and insulin concentrations
      ([Ins]p), and percent change in plasma volume (%DeltaPV) were measured, and
      esophageal temperature (Tes) thresholds for cutaneous vasodilation (THCVC) and
      sweating (THSR) at the forearm were determined. RESULTS: Posm was significantly
      increased by fructose and glucose intake compared with water alone, although
      %DeltaPV and [Na+]p were not significantly different among the three trials.
      [Ins]p was significantly higher after glucose intake than after fructose or water
      alone. THCVC and THSR were significantly higher after fructose intake than after
      glucose intake, which showed similar values to water intake. CONCLUSIONS: These
      results suggest that the Tes threshold for thermoregulation is elevated after
      fructose intake, indicating the attenuation of thermoregulatory responses,
      whereas it is not attenuated after glucose intake. These results provide a novel
      insight to better determine the carbohydrate component of oral rehydration fluids
      for preventing dehydration and/or heat disorders.

PMID- 24300127
TI  - MicroRNA-519a demonstrates significant tumour suppressive activity in laryngeal
      squamous cells by targeting anti-carcinoma HuR gene.
AB  - OBJECTIVE: This study investigated the expression and functional effects, and
      related molecular mechanisms, of microRNA-519a in laryngeal squamous cell
      carcinoma. METHODS: MicroRNA-519a and HuR messenger RNA in laryngeal squamous
      cell carcinoma were measured using reverse transcription polymerase chain
      reaction. MicroRNA-519a effects on the growth of human epithelial type 2 cells
      were tested using an MTT assay. The influence of microRNA-519a on the expression
      levels of HuR and other related genes in protein was tested by Western blotting.
      Cell cycle analyses were performed using flow cytometry. Associations between
      expression levels and patients' clinical parameters were analysed with Pearson
      correlation analysis. RESULTS: Expression of microRNA-519a in laryngeal squamous
      cell carcinoma tissues was significantly lower than in adjacent non-cancerous
      tissues. The expression of microRNA-519a was negatively associated with
      histological differentiation, tumour-node-metastasis stage, lymphatic metastasis
      and disease-free survival time. After increasing the level of microRNA-519a in
      laryngeal squamous cell carcinoma human epithelial type 2 cells, cell growth was
      inhibited and cell cycle was arrested in the G2/M phase. MicroRNA-519a down
      regulated HuR gene expression in protein levels without affecting messenger RNA
      levels. CONCLUSION: MicroRNA-519a may function as a tumour suppressor by
      inhibiting HuR expression, and may serve as a therapeutic target for laryngeal
      squamous cell carcinoma.

PMID- 24300128
TI  - Fine-tuning the size and minimizing the noise of solid-state nanopores.
AB  - Solid-state nanopores have emerged as a versatile tool for the characterization
      of single biomolecules such as nucleic acids and proteins. However, the creation
      of a nanopore in a thin insulating membrane remains challenging. Fabrication
      methods involving specialized focused electron beam systems can produce well
      defined nanopores, but yield of reliable and low-noise nanopores in commercially
      available membranes remains low and size control is nontrivial. Here, the
      application of high electric fields to fine-tune the size of the nanopore while
      ensuring optimal low-noise performance is demonstrated. These short pulses of
      high electric field are used to produce a pristine electrical signal and allow
      for enlarging of nanopores with subnanometer precision upon prolonged exposure.
      This method is performed in situ in an aqueous environment using standard
      laboratory equipment, improving the yield and reproducibility of solid-state
      nanopore fabrication.

PMID- 24300129
TI  - On the persistence of memory: soft clocks and terrestrial biosphere-atmosphere
      interactions.
AB  - The circadian clock is considered a central "orchestrator" of gene expression and
      metabolism. Concomitantly, the circadian clock is considered of negligible
      influence in the field and beyond leaf levels, where direct physiological
      responses to environmental cues are considered the main drivers of diel
      fluctuations. I propose to bridge the gap across scales by examining current
      evidence on whether circadian rhythmicity in gas exchange is relevant for field
      settings and at the ecosystem scale. Nocturnal stomatal conductance and water
      fluxes appear to be influenced by a "hard" clock that may override the direct
      physiological responses to the environment. Tests on potential clock controls
      over photosynthetic carbon assimilation and daytime transpiration are scant yet,
      if present, could have a large impact on our current understanding and modeling
      of the exchanges of carbon dioxide and water between terrestrial ecosystems and
      the atmosphere. 

PMID- 24300130
TI  - Patient perceptions of female surgeons: how surgeon demeanor and type of surgery
      affect patient preference.
AB  - BACKGROUND: As more women become surgeons, knowledge of patient perceptions is
      necessary to educate this new pool of surgeons on how to maximize patient trust
      and foster the optimal surgeon-patient relationship. MATERIALS AND METHODS:
      Patients in a general medicine clinic in San Francisco were surveyed. Study
      respondents read one of the eight short scenarios that differed by surgeon
      gender, surgery type (lung cancer versus breast cancer), and surgeon demeanor
      (more masculine--agentic versus more feminine--communal). In all scenarios, the
      surgeon was described as accomplished and well trained. After reading the short
      description, respondents rated five items from 0-5, which were averaged to create
      a measure of preference. RESULTS: Based on the 476 completed surveys, respondents
      did not have a significant preference for either female or male surgeons (P =
      0.76). We found a significant interaction in respondent choice between the
      surgeon demeanor and the type of surgery (P < 0.05). Respondents preferred an
      agentic surgeon for lung cancer surgery and a communal surgeon for breast cancer
      surgery regardless of surgeon or respondent gender. No other interactions or main
      effects were statistically significant. CONCLUSIONS: Our respondents did not
      overtly prefer a surgeon based on gender, which suggests that patients may not
      contribute to the traditional gender biases reported by female surgeons. Further
      work needs to be done to determine if our results can be replicated in different
      geographic regions and if there is gender stereotyping within the field of
      surgery.

PMID- 24300131
TI  - Evaluation of the surgical fat-filling procedure in the treatment of refractory
      cough after systematic mediastinal lymphadenectomy in patients with right lung
      cancer.
AB  - BACKGROUND: To evaluate the efficacy of the surgical fat-filling procedure (SFFP)
      in the treatment of refractory cough and quality of life (QOL) after systematic
      mediastinal lymphadenectomy in patients with right lung cancer. METHODS: This is
      a blinded, randomized, controlled clinical trial to evaluate refractory cough and
      QOL in patients after mediastinal lymphadenectomy for lung cancer. One hundred
      eligible lung cancer patients were randomly divided into two groups: the fat
      filling group and non-filling group. In the fat-filling group, post
      lymphadenectomy residual cavities (PLRCs) were filled with fatty tissue
      autografts after lymph node dissection. In the non-filling group, the PLRCs
      remained unfilled. Clinical endpoints were postoperative cough score and QOL.
      RESULTS: The SFFP did not increase intraoperative bleeding, extend operation
      time, or hospital stay. Further, night cough was significantly improved after 4
      wk in the fat-filling group after the removal of a chest drainage tube. QOL
      issues, such as emotional condition, functional status, and additional concerns,
      demonstrated a remarkable improvement in the fat-filling group at postoperative 1
      mo compared with the non-filling (control) group. CONCLUSIONS: This study
      demonstrates that filling PLRCs with fatty tissue autografts is a safe and
      partially effective treatment for refractory cough after major pulmonary
      resection and mediastinal lymphadenectomy. This novel procedure significantly
      improved patient QOL and may prove useful as a relatively safe preventive
      surgical adjunct operation for refractory cough.

PMID- 24300132
TI  - Clinical characteristics associated with ALK rearrangements in never-smokers with
      pulmonary adenocarcinoma.
AB  - OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a validated
      predictive marker to define patients with non-small cell lung cancer (NSCLC) who
      can benefit from selective ALK inhibitors. Therefore, accurate assessment of its
      prevalence and clinical characteristics is increasingly important in the
      treatment of NSCLC. Also, this ALK rearrangement was previously reported to be
      more common in patients with no smoking history or those with adenocarcinoma.
      PATIENTS AND METHODS: Never-smokers with completely resected pulmonary
      adenocarcinoma were screened for ALK rearrangements using Nanostring's gene
      expression platform. Clinicopathologic data, such as information about epidermal
      growth factor receptor (EGFR) and KRAS mutation status were retrospectively
      reviewed. RESULTS: Of 231 tumors screened, 20 (9%) had an ALK rearrangement and
      all were confirmed to be positive with immunohistochemical and fluorescent in
      situ hybridization analysis. Of the tumors with available data on the EGFR/KRAS
      mutation status, EGFR and KRAS mutation rates were 64% (69/108) and 5% (5/102),
      respectively. Amongst the tumors that were free of EGFR and KRAS mutations, the
      proportion of ALK rearrangements reached up to 33%. At the time of data cut-off,
      total of 68 tumors were recurred. Although the recurrence rate was similar
      between the ALK-positive and negative groups (30% vs. 29%), there was a tendency
      for ALK-positive tumors to recur more frequently in the pleural space (15% vs.
      5%). The five-year disease-free survival (61%) and overall survival rates (79%)
      in the ALK-positive group were similar to those in the ALK-negative group (51%
      and 83%, respectively). Even after excluding two patients treated with crizotinib
      after disease recurrence, overall survival was similar between the two groups.
      CONCLUSION: In an NSCLC subpopulation based on smoking history, histology, and
      EGFR and KRAS mutation status, the prevalence of ALK rearrangements is
      considerably high. However, ALK rearrangement status itself has no prognostic
      relevance in patients with completely resected NSCLC.

PMID- 24300133
TI  - Alterations in cytochrome P450-derived arachidonic acid metabolism during
      pressure overload-induced cardiac hypertrophy.
AB  - Cardiac hypertrophy is a major risk factor for many serious heart diseases.
      Recent data demonstrated the role of cytochrome P450 (CYP)-derived arachidonic
      acid (AA) metabolites in cardiovascular pathophysiology. In the current study our
      aim was to determine the aberrations in CYP-mediated AA metabolism in the heart
      during cardiac hypertrophy. Pressure overload cardiac hypertrophy was induced in
      Sprague Dawley rats using the descending aortic constriction procedure. Five
      weeks post-surgery, the cardiac levels of AA metabolites were determined in
      hypertrophied and normal hearts. In addition, the formation rate of AA
      metabolites, as well as, CYP expression in cardiac microsomal fraction was also
      determined. AA metabolites were measured by liquid chromatography-electrospray
      ionization-mass spectroscopy, whereas, the expression of CYPs was determined by
      Western blot analysis. Non-parametric analysis was performed to examine the
      association between metabolites formation and CYP expressions. Our results showed
      that 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs), and 5-, 12-,
      15-, and 20-hydroxyeicosatetraenoic acids (HETEs) levels were increased, whereas,
      19-HETE formation was decreased in hypertrophied hearts. The increase in EETs was
      linked to CYP2B2. On the other hand, CYP1B1 and CYP2J3 were involved in mid-chain
      HETE metabolism, whereas, CYP4A2/3 inhibition was involved in the decrease in 19
      HETE formation in hypertrophied hearts. In conclusion, CYP1B1 played cardiotoxic
      role, whereas, CYP2B2, CYP2J3 and CYP4A2/3 played cardioprotective roles during
      pressure overload-induced cardiac hypertrophy. These CYP can be valid targets for
      the development of drugs to treat and prevent cardiac hypertrophy and heart
      failure. 

PMID- 24300134
TI  - Biochemical and pharmacological assessment of MAP-kinase signaling along pain
      pathways in experimental rodent models: a potential tool for the discovery of
      novel antinociceptive therapeutics.
AB  - Injury to the peripheral or central nervous system can induce changes within the
      nervous tissues that promote a state of sensitization that may underlie
      conditions of pathological chronic pain. A key biochemical event in the
      initiation and maintenance of peripheral and central neuronal sensitization
      associated with chronic pain is the phosphorylation and subsequent activation of
      mitogen-activated protein kinases (MAPKs) and immediate early gene transcription
      factors, in particular cAMP-response element binding protein (CREB). In this
      commentary we review the preclinical data that describe anatomical and
      mechanistic aspects of nociceptive-induced signaling along nociceptive pathways
      including peripheral cutaneous axons, the dorsal root ganglia, spinal cord dorsal
      horn and cerebral cortex. In addition to the regional manifestation of
      nociceptive signaling, investigations have attempted to elucidate the cellular
      origin of biochemical nociceptive processing in which communication, i.e. cross
      talk between neurons and glia is viewed as an essential component of pathogenic
      pain development. Here, we outline a research strategy by which nociceptive
      induced cellular signaling in experimental pain models, specifically MAPK and
      CREB phosphorylation can be utilized to provide mechanistic insight into drug
      target interaction along the nociceptive pathways. We describe a series of
      studies using nociceptive inflammatory and neuropathic pain models to investigate
      the effects of known pain therapeutics on nociceptive-induced biochemical
      signaling and present this as a complementary research strategy for assessing
      antinociceptive activity useful in the preclinical development of novel pain
      therapeutics. 

PMID- 24300135
TI  - Preoperative statins and limb salvage after lower extremity revascularization in
      the Medicare population.
AB  - BACKGROUND: Statins stabilize atherosclerotic plaque, decrease mortality after
      surgical procedures, and are linked to anti-inflammatory effects. The objective
      of this study was to evaluate preoperative administration of statins and
      longitudinal limb salvage after lower extremity endovascular revascularization
      and lower extremity open surgery. METHODS AND RESULTS: Patients were selected
      from 2007 to 2008 Medicare claims using the International Classification of
      Diseases, Ninth Revision, Clinical Modification, diagnosis codes for claudication
      (N=8128), rest pain (N=3056), and ulceration/gangrene (N=11,770) and Current
      Procedural Terminology codes for endovascular revascularization (N=14,353) and
      open surgery (N=8601). Half (N=11,687) were identified as statin users before
      revascularization using Part D files. Amputations were identified using Current
      Procedural Terminology codes. Statin users compared with nonusers had lower
      amputation rates at 30 days (11.5% versus 14.4%; P<0.0001), 90 days (15.5% versus
      19.3%; P<0.0001), and 1 year (20.9% versus 25.6%; P<0.0001). Survival analysis
      demonstrated improved limb salvage during 1 year for statin users compared with
      nonusers for the diagnosis of claudication (P=0.003), a similar trend for rest
      pain (P=0.061), and no improvement for ulceration/gangrene (P=0.65). CONCLUSIONS:
      Preoperative statins were associated with improved 1-year limb salvage after
      lower extremity revascularization. The strongest association was found for
      patients with the diagnosis of claudication. Statins seem to be underused among
      Medicare patients with peripheral artery disease. Further evaluation of the use
      of preoperative statins and the potential benefits for peripheral vascular
      interventions is warranted.

PMID- 24300136
TI  - Impact of transcatheter pulmonary valve replacement on biventricular strain and
      synchrony assessed by cardiac magnetic resonance feature tracking.
AB  - BACKGROUND: Transcatheter pulmonary valve (TPV) replacement is an emerging
      therapy intended to restore pulmonary valve function in patients with right
      ventricular outflow tract conduit dysfunction; the impact of this technique on
      ventricular strain and synchrony is not known. METHODS AND RESULTS: Cardiac
      magnetic resonance and ECG data acquired at 1 center as part of the US Melody TPV
      trial were analyzed. Biventricular strain and mechanical synchrony measurements
      were made based on short-axis and 4-chamber steady-state free precession images
      using feature tracking software. Post- versus pre-TPV replacement findings were
      compared for all patients (n=31) and subgroups with predominant pulmonary
      regurgitation (n=13) or stenosis (n=18). Most patients had tetralogy of Fallot
      (18/31). After TPV replacement, left ventricular (LV) circumferential strain
      increased for the whole cohort (P<0.001) and both subgroups (pulmonary
      regurgitation P=0.01; pulmonary stenosis P=0.02). LV longitudinal strain
      increased for the whole cohort (P=0.02) and pulmonary regurgitation subgroup
      (P=0.05); circumferential right ventricular strain increased for the pulmonary
      stenosis group only (P=0.05). LV longitudinal synchrony improved significantly in
      the pulmonary regurgitation group (maximum wall delay P=0.03; cross-correlation
      delay P=0.01). Electric measures of synchrony did not improve. CONCLUSIONS: In
      patients with right ventricular outflow tract conduit dysfunction, TPV
      replacement is associated with improved global LV strain, as well as improved
      right ventricular strain and LV synchrony in subgroups. Given the associations
      between strain and synchrony and clinical outcomes, these findings support
      potential long-term benefits of TPV replacement.

PMID- 24300137
TI  - [Emphasis on study for clinical treatment of venous thromboembolism].

PMID- 24300138
TI  - [Prevention and treatment of vein thrombosis in patients with orthopedic
      surgery].

PMID- 24300139
TI  - [Analysis of guidelines for the treatment of lower extremity deep vein
      thrombosis].

PMID- 24300140
TI  - [The prevention and treatment of venous thromboembolic disease in pregnancy].

PMID- 24300141
TI  - [Mechanism and role of venoactive drugs in the treatment of primary chronic
      venous disease].

PMID- 24300142
TI  - [The analysis of curative affection/risk and mastery of degree in neurosurgical
      management].

PMID- 24300143
TI  - [Outcome comparisons of anticoagulation, systematic thrombolysis and catheter
      directed thrombolysis in the treatment of lower extremity acute deep venous
      thrombosis].
AB  - OBJECTIVE: To explore the outcomes of anticoagulation, systematic thrombolysis
      and catheter-directed thrombolysis (CDT) in the treatment of lower extremity
      acute deep venous thrombosis (DVT). METHODS: The clinical data of 152 patients
      with lower extremity acute DVT from January 2005 to December 2009 were analyzed
      retrospectively. They were divided into single anticoagulation group (A),
      systematic thrombolysis plus anticoagulation group (B) and CDT plus
      anticoagulation group (C).Follow-up studies were performed to inquire about
      patient symptoms, check the status of affected extremities and examine venous
      patency with venous ultrasonography or anterograde venous radiography. The
      incidence rate of post-thrombotic syndrome (PTS) was evaluated with the Villalta
      score while the quality of life with CIVIQ-2 questionnaire. And the post
      discharge anticoagulation time and use of compression stockings were analyzed in
      each group. RESULTS: (1)The venous patency rate was 69.1%, 70.8%, 85.1% in groups
      A, B and C respectively. The differences was significant between groups A and C
      (P < 0.05). The differences was insignificant between groups C and B (P > 0.05).
      And the venous patency rate of group C was higher than that of group B. The
      difference was insignificant between groups A and B (P > 0.05).Such remodeling
      effects as venous valvular destruction and intravenous wall thickening were
      observed in PTS patients with venous ultrasonography and anterograde venous
      radiography. (2) The incidence of PTS was 56.8%, 54.2%, 38.3% in groups A, B and
      C. Compared with groups A and B, the difference was significant in group C (P <
      0.05). The difference was insignificant between groups A and B (P > 0.05). (3)
      CIVIQ-2 score was 20.2 +/- 14.4, 20.1 +/- 12.5, 16.6 +/- 11.0 in groups A, B and
      C. Compared with groups A and B, the difference was insignificant in group C (P >
      0.05). And it was lower in group C than groups A and B. (4) The differences of
      average anticoagulant time and compression stocking use were insignificant in 3
      groups (P > 0.05). CONCLUSION: Compared with anticoagulant and systematic
      thrombolysis, a combination of CDT and anticoagulation may reduce the risk for
      PTS, alleviate clinical symptoms and improve quality of life.

PMID- 24300144
TI  - [Phenotypic detection and structure analysis of a PC missense mutation
      (Met406Ile) resulted in venous thromboembolism].
AB  - OBJECTIVE: To identify the phenotypic detection and structure analysis of a
      protein C (PC) missense mutation (Met406Ile) resulting in venous thromboembolism.
      METHODS: Pedigree research was performed for a hereditary PC deficiency pedigree.
      Chromogenic assay was used for phenotypic diagnosis to detect the AT activity.
      All 9 exons were amplified by polymerase chain reaction (PCR) and direct
      sequencing analysis was performed for PCR products. The corresponding mutation
      sites of family members were detected.Homology modeling was used for
      reconstructing mutant PC construction. The effects of construction change were
      analyzed. RESULTS: The PC activities of proband and 4 family members decreased to
      different extents by 29.7%, 42.2%, 42.4%, 67.3% and 70.7% respectively. Among
      them, the proband and other three family members carried the same mutation
      (c.1218G > A, Met406Ile) while another family member had a PC polymorphism
      (rs1799810). Homology modeling showed that VDW's interaction radius of amino
      acids decreased after mutation (Met406Ile).In particular, the radius of Gly418:C
      and Ile406CG2, Gly418:C and Ile406HG23, Leu419:N and Ile406:HG23 decreased to
      2.0733a, 1.620 45a and 1.446 52a respectively. Compared with normal PC, the
      interaction energy of mutant PC rose from -8.504 54 to 1210.04 kal/mol. And the
      change of VDW interaction energy was significant. CONCLUSION: The mechanism of
      this pedigree is caused by PROC gene missense mutation on exon 9 (c.1218G > A,
      Met406Ile). The regional amino acids of mutant PC collide with each other and
      lead to an instability of PC reconstruction.

PMID- 24300145
TI  - [Analyses of risk factors for deep vein thrombosis in lower extremities].
AB  - OBJECTIVE: To explore the risk factors of deep vein thrombosis (DVT) in lower
      extremities. METHODS: Retrospective data analyses were performed for a total of
      1264 DVT patients at our department from January 2010 to December 2012. RESULTS:
      Among them, 984 cases (77.85%) were over 40 years old, no overt cause was found
      for 642 cases (50.79%), 142 cases (11.23%) had a clear history of trauma before
      onset (without surgery). Among 316 recurrent postoperative cases, there were the
      surgical histories of orthopedics (n = 142, 11.23%), gynecology (n = 90, 7.12%),
      general practice (n = 42, 3.32%), vascular (n = 23, 1.82%), urological (n = 12,
      0.94%) and others (n = 7, 0.55%). Ten cases (0.79%) occurred after suffering
      bedridden chronic diseases. And 20 cases (1.58%) were caused by conditions during
      pregnancy or postpartum period.had Malignant tumors were found in 25 (1.98%)
      patients. After long-term uses of hormones, 10 patients (0.79%) of rheumatoid
      arthritis had a recurrence.Owing to varicose veins, 27 patients (2.14%) recurred.
      Eight patients (0.63%) had a history of drug abuse, 2 cases (0.16%) suffered
      depression and 62 cases (4.9%) were recurrent. CONCLUSION: There are many
      causative factors of DVT so that prevention is of great importance. We should pay
      more attention to the prevention and treatment of high-risk DVT patients.

PMID- 24300146
TI  - [Application of VEEG+SEMG in diagnosing different motor seizure types].
AB  - OBJECTIVE: To explore the value of video-electroencephalography plus surface
      electromyography (VEEG+SEMG) in providing theoretic rationales for clinical
      diagnosis of different motor seizure types and differentiating the application
      value of paroxysmal diseases. METHODS: A total of 116 suspected and repetitive
      motion epileptics underwent VEEG+SEMG from 2009 to 2012. According to their
      clinical features, different muscles were selected to record electromyography
      (EMG) under different activations and stimulations (bodily movement and posture
      activation, touching, sound stimulus, tapping tendons and arms straight test,
      etc) and monitor their seizure states. RESULTS: Among 68 patients, 567 attacks
      were recorded, including 443 epileptic seizures in 41 patients (229 epileptic
      mycological seizures in 22 patients, 95 tonic seizures in 8, 118 epileptic spasms
      in 10 and 1 atonic seizure in 1). The average durations of different epileptic
      motor seizures were (0.16 +/- 0.04), (2.9 +/- 2.4), (1.4 +/- 0.8) and 2 s
      respectively. Their features of ictal EEG and SEMG varied.Non-epileptic seizures
      were recorded, including 43 non-epileptic myoclonus (NEMS) in 2 patients 81 PKD
      in 25. The primary differential diagnoses of epileptic motor seizures were NEMS
      and paroxysmal kinesigenic dyskinesia (PKD). CONCLUSION: VEEG+SEMG is a reliable
      tool for diagnosing different types of epileptic seizures and differentiating
      among paroxysmal diseases.

PMID- 24300147
TI  - [Comparison of (18)F-FDG PET/CT and enhancement CT in diagnosing regional lymph
      node metastasis of colorectal cancer].
AB  - OBJECTIVE: The aim of this study was to compare the diagnostic value of (18)F-FDG
      PET/CT with contrast CT for regional lymph node metastasis of colorectal cancer.
      METHODS: Imaging results of 40 patients with colorectal cancer were
      retrospectively reviewed, and all the patients underwent both abdomen contrast CT
      and (18)F-FDG PET/CT imaging. Final diagnosis was made by histopathology.
      RESULTS: 20 colorectal cancer patients were verified with lymph node metastasis
      while the other 20 patients were absent. Finally, (18)F-FDG PET/CT produced 4
      false-positive patients and 3 false-negative patients. (18)F-FDG PET/CT displayed
      sensitivity 85.0% (17/20), specificity 80.0% (16/20), positive predictive value
      81.0% (17/21), negative predictive value 84.2% (16/19) and accuracy 82.5% (33/40)
      in the diagnosis of lymph node metastasis. Contrast CT produced 5 false-positive
      patients and 8 false-negative patients. Contrast CT had the sensitivity 60.0%
      (12/20), specificity 75.0% (15/20) , positive predictive value 70.6% (12/17),
      negative predictive value 65.2% (15/23) and accuracy 67.5% (27/40). Sensitivity
      and specificity of PET/CT was better than of contrast CT, but no statistically
      significant difference between PET/CT and contrast CT (P = 0.478, P = 0.893; P =
      0.344. Fisher's exact test and McNemar test). CONCLUSION: Sensitivity and
      specificity of PET/CT was better than of contrast CT, but no statistically
      significant difference. Clinical works also need to select the appropriate
      inspection methods based on the patient's situation.

PMID- 24300148
TI  - [Retrospective analysis of effectiveness of intensity-modulated radiotherapy
      combined with chemotherapy or not for locoregionally advanced nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To analyze the effectiveness and toxicity of intensity-modulated
      radiotherapy (IMRT) combined with chemotherapy or not for locoregionally advanced
      nasopharyngeal carcinoma. METHODS: A total of 226 patients with locoregionally
      advanced nasopharyngeal carcinoma were retrospectively reviewed and classified
      into three groups:67 patients treated by radiotherapy alone (RT group), 82
      patients by concurrent chemoradiotherapy (CRT group) and 77 patients by
      cisplatin+5-fluorouracil (PF regimen) combined with CRT (PF+CRT group). All
      patients using IMRT technique.Outcomes were overall survival, failure patterns,
      and toxicities. RESULTS: For the RT, CRT and PF+CRT group, the 5-year overall
      survival rate was 67.6%, 74% and 71.1% (P = 0.664), respectively; progress-free
      survival rate 66.9%, 72.6% and 75.6% (P = 0.410); relapse-free survival rate
      82.4%, 86.4% and 86.8% (P = 0.447) and distant metastasis-free survival rate
      83.8%, 83.8% and 85.8% (P = 0.827). Significantly more grade 3-4 acute toxicities
      happened in patients treated by chemotherapy (P = 0.002). CONCLUSION: Comparing
      with IMRT alone, cisplatin-IMRT or PF regimen induction chemotherapy plus
      cisplatin-IMRT do not significantly improve survival, but increased grade 3-4
      acute toxicities.

PMID- 24300149
TI  - [Posterior C1-C2 transarticular screw fixation for atlantoaxial instability
      assisted by intraoperative 3-dimensional fluoroscopy-based navigation].
AB  - OBJECTIVE: To assess the feasibility, efficacy and indication of posterior C1-C2
      transarticular screw fixation for atlantoaxial instability assisted by
      intraoperative 3-dimensional fluoroscopy-based navigation. METHODS: From November
      2005 to October 2012, 58 patients with atlantoaxial instability underwent
      posterior C1-C2 transarticular screw fixation assisted by intraoperative 3
      dimensional fluoroscopy-based navigation. Those with excellent atlantoaxial
      reduction and no need for decompression underwent percutaneously minimally
      invasive procedures. Operative duration, blood loss volume, reduction of
      atlantoaxial joints and postoperative neurovascular complications were recorded.
      Screw positions were studied by postoperative computed tomography (CT) and
      divided into 3 categories. The follow-up period was at least 3 months. Local
      symptoms (assessed by visual analogue scale (VAS) score), neurological conditions
      (Nurick classification) and bone graft fusion were evaluated. RESULTS: Among
      them, the procedure was either open surgery (n = 51) or percutaneously minimally
      invasive surgery (n = 7). A total of 111 screws were placed satisfactorily. Five
      patients underwent only unilateral C1-C2 transarticular screw fixation. No severe
      complications were encountered. The mean operative duration was 202.2 +/- 54.2
      minutes and the average volume of blood loss 412.6 +/- 281.2 ml. And the values
      were comparable to those for the traditional fluoroscopy-guided free-hand
      procedures. No statistical significance existed between open and percutaneously
      minimally invasive procedures in operative duration, blood loss volume and
      precision of screw placement. The patients with incompletely reduced C1-C2
      dislocation had comparable clinical outcomes with those with complete reduction.
      After a 3-month follow-up, all of them showed significant improvements of local
      symptoms. VAS score decreased from 4.5 +/- 1.3 preoperatively to 0.7 +/- 0.8
      postoperatively while the Nurick classification improved from 2.4 +/- 1.1 to 0.6
      +/- 1.0. And bone graft fusion was satisfactory. CONCLUSIONS: Posterior C1-C2
      transarticular screw fixation for atlantoaxial instability assisted by
      intraoperative 3-dimensional fluoroscopy-based navigation is both feasible and
      safe. Combined with minimally invasive techniques, this procedure may achieve
      greater precision and minimal invasion.

PMID- 24300150
TI  - [Molecular epidemiological characteristics of HIV-1 B'/C strains in Beijing].
AB  - OBJECTIVE: To analyze the molecular epidemiological characteristic of HIV-1 B'/C
      strains prevalent in Beijing. METHODS: Plasma samples were collected from 200
      newly diagnosed HIV-1 B'/C individuals reported during 2006 to 2010 in Beijing.
      The gag gene fragments were amplified from RNA template extracted from plasma
      with reverse transcription (RT) and nested polymerase chain reaction (PCR). And
      the sequences were analyzed by phylogenetic methods and Entropy analysis.
      RESULTS: A total of 159 sequences were successfully amplified from the gag genes
      of which 147 was CRF07_BC and 12 CRF08_BC. There were 3 main sub-clusters in
      CRF07_BC phylogenetic tree and they were named as sub-cluster IDU-Max (89
      sequences), sub-cluster IDU-Min (22 sequences) and sub-cluster MSM (34 sequences)
      based on transmission.No international reference strain was closely related with
      these three sub-clusters except for one strain identified in Taiwan. All CRF07_BC
      recombinant strains were remarkable for their low interpatient diversity in gag
      genes (3.7%, 3.3% and 2.0% for isolates from IDU-Max, IDU-Min and MSM
      respectively).When compared with sub-cluster IDU-Max, there were 32 and 41
      significantly different sites of nucleotide polymorphism compositions in sub
      clusters IDU-Min and MSM. CONCLUSION: This is the first report of describing the
      existence of three main epidemic sub-clusters in CRF07_BC strains prevalent in
      Beijing. And IDU-Max sub-cluster is the dominant strain. The CRF07_BC in Beijing
      are less diverse than other strains and may be derived from a common ancestor.

PMID- 24300151
TI  - [Detection significance of Th17 cells in peripheral blood of patients with
      rheumatoid arthritis in clinical remission].
AB  - OBJECTIVE: To explore the significance and evaluate the early structural erosion
      through the expressions of Th17 cells in peripheral blood of patients with
      rheumatoid arthritis (RA) in clinical remission. METHODS: A total of 41 active RA
      patients without structural erosion were selected. Intracelluar flow cytometric
      detection of Th17 cells in peripheral blood was performed. And the supernatant
      level of interleukin (IL)-17A was determined simultaneously in RA patients and
      control groups at baseline and endpoint of 24-month therapy. The correlations
      were analyzed between Th17 cells and RA disease activity index DAS28. They were
      classified into radiographic progression (P, n = 10) and radiographic non
      progression groups (NP, n = 26) by the Sharp/van der Heijde score (SHS) at the
      endpoint. The differences of Th17 cells and IL-17A levels were analyzed between P
      (SHS > 0.5) and NP groups (SHS <= 0.5). RESULTS: The expression of Th17 cells in
      active RA patients was significantly higher than that of controls [(1.63 +/-
      0.45)% vs (0.91 +/- 0.26)%, P < 0.01]. And the results of IL-17A level were
      similar [1510 +/- 280) vs (320 +/- 31) ng/L, P < 0.05]. The expression of Th17
      cells was positively correlated with DAS28 score (r = 0.87, P < 0.01). Thirty-six
      RA patients were followed up at the endpoint and all of them stayed in clinical
      remission (DAS28 < 2.6). The peripheral blood expressions of Th17 cells of P
      group were significantly higher than those of NP group . At the same time, no
      differences of IL-17A levels existed between two groups. CONCLUSION: Structural
      erosion still progresses in some RA patients despite an apparent clinic
      remission. And a high-level peripheral expression of Th17 hints at structural
      erosion.

PMID- 24300152
TI  - [Effects of statins upon bone mineral density in postmenopausal women with
      hypercholesterolemia].
AB  - OBJECTIVE: To explore the effects of statins upon bone mineral density (BMD) and
      bone metabolic markers in postmenopausal women with hypercholesterolemia.
      METHODS: A prospective study was conducted for 100 women receiving treatment from
      January 2011 to August 2012 and meeting the inclusion criteria of osteopenia or
      osteoporosis with hypercholesterolemia postmenopausal. They were randomly divided
      into treatment group on atorvastatin 10 mg once daily and control group. The
      parameters of lumbar BMD, bone resorption markers of type I collagen cross-linked
      C-telopeptide (CTX) , bone synthesis markers procollagen type I N-terminal
      peptide (PINP) were compared between two groups after half a year and one year.
      RESULTS: There was an upward trend of lumbar spine BMD and PINP in the treatment
      group at half a year and one year compared with the control group. And two groups
      had significant difference (P < 0.05). Although two groups had no significant
      difference in all parameters at half a year, the values of lumbar spine BMD and
      PINP were higher in the treatment group at one year than the control group. Two
      groups had significant difference (P < 0.05). CONCLUSIONS: Statins can help
      maintain or increase bone mass of hypercholesterolemic menopausal women through
      promoting bone synthesis.

PMID- 24300153
TI  - [A case-control mortality study of migrant pregnant women in Zhejiang province].
AB  - OBJECTIVE: To explore the mortality factors of migrant pregnant women and learn
      the healthcare utilization status to provide efficient interventions. METHODS: A
      case-control study was conducted in Zhejiang province with a case-control ratio
      of 1: 4. Cases included migrant pregnant women who died. And controls were
      migrant pregnant women who survived and matched with single birth, age, hospital
      and gestational weeks. A questionnaire was used to survey social and demographic
      factors, healthcare status during antenatal or postpartum period and delivery
      conditions, etc. RESULTS: Seventy-two cases and 288 controls were recruited.
      There were significant differences in socio-demographic, antenatal care and
      obstetric complications between two groups (P < 0.05). No prenatal examination
      was an important factor affecting maternal mortality by multivariate conditional
      Logistic regression. CONCLUSION: Prenatal examination is an important influencing
      factor of maternal mortality. And improving the ability of utilizing health care
      system is an efficient method of lowering the migrant maternal mortality.

PMID- 24300154
TI  - [Diagnostic value of magnetic resonance imaging in special-site ectopic
      pregnancy].
AB  - OBJECTIVE: To explore the magnetic resonance imaging (MRI) features and
      diagnostic value of special-site ectopic pregnancy. METHODS: The MRI features of
      special-site ectopic pregnancy on 39 pathologically confirmed cases were
      retrospectively analyzed. All cases received ultrasonic inspection, MRI plain
      scan and 11 cases underwent enhanced scan. RESULTS: In 39 cases, there were 3
      cases of interstitial tubal pregnancy (n = 3), cornual pregnancy (n = 8) and
      uterine scar pregnancy (n = 28). The accuracy rates of location and diagnosis
      were 94.9% and 82.1% respectively. And they were both higher than the rates of
      ultrasound. They were classified into two groups by clinical outcomes:pregnancy
      and miscarriage. In 22 cases of pregnancy, there were sac in sac (n = 9) and
      complete fertilized egg (n = 13). In 17 cases of miscarriage, there were
      irregular honeycomb (n = 7), ring (n = 6) and mass (n = 4). Among 11 enhanced
      cases, there were significant enhancement (n = 4), flake or cord-like enhancement
      (n = 5), a little strengthen on edge (n = 1) and no enhancement (n = 1). The
      group had intrauterine decidual tissue hyperplasia (n = 22), ovarian cyst (n =
      8), pelvic fluid (n = 6), adenomyosis (n = 3), fibroid (n = 2), endometriosis in
      pelvic and abdominal wall scar area (n = 1) and mild hydrops in right kidney and
      ureter (n = 1). CONCLUSION: The MRI features of special-site ectopic pregnancy
      are characteristic and important for clinical treatment.

PMID- 24300155
TI  - [Microsurgical treatment regimens of cavernous sinus hemangioma].
AB  - OBJECTIVE: To analyze the microsurgical treatment regimens of cavernous sinus
      hemangioma. METHODS: The microsurgical experiences were reviewed and analyzed for
      17 cases of operatively and pathologically confirmed cavernous sinus cavernous
      hemangioma at our hospital from January 2008 to January 2012. There were 6 males
      and 11 females with an average age of 48.5 years. RESULTS: Among them, there were
      total (n = 14) and subtotal (n = 3) resection. And there was no occurrence of
      postoperative mortality. According to the results of imaging follow-up, total
      resection cases had no recurrence while subtotal residual tumor was progression
      free after radiotherapy. Oculomotor, abducens and trigeminal nerves retained
      varying degrees of neurological function at 3-6 months postoperation. CONCLUSION:
      Based on the size of tumor and growth direction, appropriate surgical approaches
      may be selected. And a combination of skilled microsurgical techniques and proper
      resection may reduce bleeding and facilitate total tumor removal so as to reduce
      the degree of neurological deficits and improve the long-term postoperative
      quality-of-life.

PMID- 24300156
TI  - [Reliving refractory pain of spinal metastasis patients with radiofrequency
      ablation through transforaminal endoscopy].
AB  - OBJECTIVE: To explore the short-term outcomes of radiofrequency ablation
      treatment of bone metastasis. METHODS: Between November 2011 and November 2012, a
      total of 18 cases were retrospectively reviewed. They underwent resection of bone
      metastasis with radiofrequency ablation through transforaminal endoscopic spine
      system. According to the Tomita classification system, the classifications were
      type 5 (n = 8), type 6 (n = 4) and type 7 (n = 6). There were 8 males and 10
      females with a median age of 52.1 (32-76) years. The primary lesions were breast
      cancer (n = 5), carcinoma of prostate (n = 3), digestive cancer (n = 4), thyroid
      carcinoma (n = 2)and lung cancer (n = 4). And two cases had pathologic fracture.
      RESULTS: The operative duration was 118 (90-180) min and blood loss volume 30.6
      (10-60) ml. All incisions achieved excellent healing.One case of pneumonia
      recovered with antibiotic. The postoperative visual analogue scale (VAS) scores
      were 2.4 +/- 0.4, 2.6 +/- 0.6, 3.0 +/- 0.3 and 2.8 +/- 0.7. CONCLUSION:
      Radiofrequency ablation through transforaminal endoscopy may be a safe and
      efficacious option for refractory pain with bone metastasis, especially for those
      with uncontrolled pain. This procedure is mini-invasive and causes less bleeding.

PMID- 24300157
TI  - [Effect and mechanism of marrow stromal cells within cerebrospinal fluid on SOD1
      transgenic mice].
AB  - OBJECTIVE: To explore the effect and mechanism of murine marrow stromal cells
      (MSCs) within cerebrospinal fluid (CSF) on Cu/Zn superoxide dismutase 1 (SOD1)
      transgenic mice. METHODS: A dose of 5*10(5) MSCs was injected into the CSF of
      SOD1 transgenic mice at the ages of 8, 10 and 12 weeks.Hanging wire test and
      motor neuron counts were used to assess disease progression of SOD1 mice. To
      examine the glial activation in murine lumbar spinal cord at 15 weeks of age, the
      sections were stained with antibody to CD11b and GFAP through
      immunohistochemistry.In vitro, mRNA expression of neurotrophin of MSCs was
      analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Compared with vehicle-treated mice, intrathecally transplanted MSCs enhanced
      motor performance and decreased motor neuron loss. An intrathecal injection of
      MSCs inhibited microglial (52 +/- 7 vs 38 +/- 7; F = 69.3, P = 0.02) and
      astrocyte (79 +/- 9 vs 63 +/- 9; F = 40.7, P = 0.03) activity in lumbar spinal
      cord at the age of 15 weeks of age. MSCs cultured in an inflammatory environment
      expressed a higher mRNA level of neurotrophin (P < 0.05). CONCLUSION: A CSF
      administration of MSCs has therapeutic effects on SOD1 mice. And the meditation
      of MSCs may be achieved through inhibiting neuroinflammation and secreting a
      variety of trophic factors.

PMID- 24300158
TI  - Young men's views toward the barriers and facilitators of Internet-based
      Chlamydia trachomatis screening: qualitative study.
AB  - BACKGROUND: There is a growing number of Internet-based approaches that offer
      young people screening for sexually transmitted infections. OBJECTIVE: This paper
      explores young men's views towards the barriers and facilitators of implementing
      an Internet-based screening approach. The study sought to consider ways in which
      the proposed intervention would reach and engage men across ages and
      socioeconomic backgrounds. METHODS: This qualitative study included 15 focus
      groups with 60 heterosexual young men (aged 16-24 years) across central Scotland,
      drawn across age and socioeconomic backgrounds. Focus groups began by obtaining
      postcode data to allocate participants to a high/low deprivation category. Focus
      group discussions involved exploration of men's knowledge of chlamydia, use of
      technology, and views toward Internet-based screening. Men were shown sample
      screening invitation letters, test kits, and existing screening websites to
      facilitate discussions. Transcripts from audio recordings were analyzed with
      "Framework Analysis". RESULTS: Men's Internet and technology use was
      heterogeneous in terms of individual practices, with greater use among older men
      (aged 20-24 years) than teenagers and some deprivation-related differences in
      use. We detail three themes related to barriers to successful implementation:
      acceptability, confidentiality and privacy concerns, and language, style, and
      content. These themes identify ways Internet-based screening approaches may fail
      to engage some men, such as by raising anxiety and failing to convey
      confidentiality. Men wanted screening websites to frame screening as a serious
      issue, rather than using humorous images and text. Participants were encouraged
      to reach a consensus within their groups on their broad design and style
      preferences for a screening website; this led to a set of common preferences that
      they believed were likely to engage men across age and deprivation groups and
      lead to greater screening uptake. CONCLUSIONS: The Internet provides
      opportunities for re-evaluating how we deliver sexual health promotion and engage
      young men in screening. Interventions using such technology should focus on
      uptake by age and socioeconomic background. Young people should be engaged as
      coproducers of intervention materials and websites to ensure messages and content
      are framed appropriately within a fast-changing environment. Doing so may go some
      way to addressing the overall lower levels of testing and screening among men
      compared with women.

PMID- 24300159
TI  - Intramuscular cysticercosis: starry sky appearance.

PMID- 24300160
TI  - Risk of venous thromboembolism in patients treated for bacterial infection in the
      community with outpatient parenteral antimicrobial therapy.
AB  - BACKGROUND: It is recommended that venous thromboembolism (VTE) prophylaxis be
      considered for patients receiving outpatient parenteral antimicrobial therapy
      (OPAT), but there is no published data to quantify VTE risk in this patient
      group. AIM AND METHOD: The aim of this retrospective cohort study was to
      establish VTE incidence in patients managed through an OPAT service and assess
      utility of a common VTE prediction score normally used for inpatients.
      Consecutive episodes of OPAT between May 2009 and May 2012 were included.
      Patients on long-term anti-coagulants, those with an established indication for
      extended, outpatient VTE prophylaxis (i.e. patients referred to OPAT following
      hip or knee arthroplasty) were excluded. The Padua VTE Prediction Score was
      retrospectively applied to the cohort. The primary outcome was incidence of
      symptomatic VTE during or up to 90 days after completion of OPAT treatment.
      RESULTS: There were 780 included patient episodes; 105 (13.5%) patients had a
      Padua VTE risk score >3; no patients received pharmacological VTE prophylaxis
      during OPAT treatment. During or up to 90 days following OPAT, two proximal lower
      limb DVTs were diagnosed, giving VTE incidence of 2/780 (0.26%, 95% CI: 0.03
      0.92%), and there were eight deaths of which none were suspected to be related to
      VTE. There was one intracranial haemorrhage associated death. CONCLUSION: This
      retrospective cohort study found a low incidence of VTE in OPAT patients, and
      does not support routine application of inpatient VTE prophylaxis algorithms to
      patients treated for infection in the community.

PMID- 24300161
TI  - Current status of standardization of acupuncture and moxibustion in China.
AB  - With the wide-spread and application of acupuncture and moxibustion, the demand
      of its standardization construction is increasingly prominent. On the basis of
      further investigation into the standards of acupuncture and moxibustion in China,
      this article summarize the research status of Chinese standardization of
      acupuncture and moxibustion, analyse some problems existing in current
      construction of acupuncture and moxibustion standardization, and put forward
      several strategies for moving forward, in order to show an overall and objective
      understanding of acupuncture and moxibustion standardization. 

PMID- 24300162
TI  - Can mobile technology improve response times of junior doctors to urgent out-of
      hours calls? A prospective observational study.
AB  - BACKGROUND: The Hospital at Night system has been widely adopted to manage Out-of
      Hours workload. However, it has the potential to introduce delays and corruption
      of information. The introduction of newer technologies to replace landlines,
      pagers and paper may ameliorate these issues. AIM: To establish if the
      introduction of a Hospital at Night system supported by a wireless taskflow
      system affected the escalation of high Early Warning Scores (EWSs) to medical
      attention, and the time taken to medical review. DESIGN: Prospective 'pre and
      post' observational study in a teaching hospital in the UK. METHODS: Review of
      observation charts and medical records, and data extraction from the electronic
      taskflow system. RESULTS: The implementation of a technology-supported Hospital
      at Night system was associated with a significant decrease in time to
      documentation of initial review in those who were reviewed. However, there was no
      change in the proportion of those with a high EWS that were reviewed, and
      throughout the study a majority of patients with high EWSs were not reviewed in
      accordance with guidelines. CONCLUSION: Introduction of a Hospital at Night
      system supported by mobile technology appeared to improve the transfer of
      information, but did not affect the nursing decision whether to escalate abnormal
      findings.

PMID- 24300163
TI  - Comprehensive definition of a giant ascending aortic pseudoaneurysm.

PMID- 24300164
TI  - Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of
      previous cases.
AB  - Autosomal dominant cerebellar ataxia type I is a heterogeneous group of
      spinocerebellar ataxias with variable neurologic presentations, with age of onset
      varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is
      composed mainly of 3 prevalent spinocerebellar ataxia types with different
      pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23),
      spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The
      shared pathogenic mutational event is the expansion of the CAG repeat that
      results in polyglutamine extended stretches in the encoded proteins. CAG repeat
      disorders generally show the phenomenon of anticipation, which is more often
      associated with paternal transmission. In this report, we describe a patient with
      infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the
      disease from his father (47 CAG repeats). We have summarized the clinical,
      neuroimaging, electroencephalographic (EEG), and molecular data of previous cases
      and attempt to highlight the most consistent findings. Our intent is to help
      treating clinicians to suspect this disorder and to offer timely genetic
      counseling for a currently potentially untreatable disorder.

PMID- 24300165
TI  - National integration of mental health providers in VA home-based primary care: an
      innovative model for mental health care delivery with older adults.
AB  - PURPOSE OF THE STUDY: To promote mental health (MH) service access and quality
      for veterans with complex and chronic medical, social, and behavioral conditions,
      the U.S. Department of Veterans Affairs (VA) has integrated a full-time MH
      provider into each VA home-based primary care (HBPC) team. The goal of the
      current evaluation is to examine the nature and extent to which MH care processes
      and practices have been integrated into HBPC nationally. DESIGN AND METHODS:
      Separate surveys assessing the integration of a wide range of MH care practices
      and HBPC team processes were sent to MH providers and program directors in each
      HBPC program in 2010. RESULTS: A total of 132 MH providers representing 119 HBPC
      programs, and 112 program directors completed the surveys. The most common
      clinical issues addressed by MH providers were depression, coping with illness
      and disability, anxiety, caregiver/family stress, and cognitive evaluation. Other
      team members typically conducted initial MH screenings, with MH providers' time
      focusing on cases with identified needs. Approximately 40% of MH providers' time
      was devoted to direct clinical care. Significant time was also spent on team
      activities, driving, and charting. IMPLICATIONS: Integration of MH services into
      HBPC is feasible and facilitates service access for a vulnerable population.
      Mental health care delivery in HPBC generally involves a high degree of
      interdisciplinary practice. Mental health integration into HBPC may serve as a
      model for other systems interested in promoting MH care delivery among homebound
      and other older individuals.

PMID- 24300166
TI  - Contribution of a phytotoxic compound to the allelopathy of Ginkgo biloba.
AB  - Ginkgo (Ginkgo biloba L.) has not changed over 121 million years. There may be
      unknown special strategy for the survival. Gingko litter inhibited the growth of
      weed species ryegrass (Lolium multiflorum L.). The inhibition was greater with
      the litter of the close position than that of the far position from the gingko
      tree. A phytotoxic substance, 2-hydroxy-6-(10-hydroxypentadec-11-enyl)benzoic
      acid (HHPEBA) was isolated in the litter. HHPEBA concentration was greater in the
      litter of the close position than that of the far position from the tree. HHPEBA
      inhibited the ryegrass growth at concentrations greater than 3 MUM. HHPEBA was
      estimated to be able to cause 47-62% of the observed growth inhibition of
      ryegrass by the gingko litter. Therefore, HHPEBA may contribute to the inhibitory
      effect caused by ginkgo litter and may provide a competitive advantage for gingko
      to survive through the growth inhibition of the neighboring plants. 

PMID- 24300167
TI  - Q wave area for stratification of global left ventricular infarct size:
      comparison to conventional ECG assessment using Selvester QRS-score.
AB  - OBJECTIVES: Left ventricular (LV) infarct size is a prognostic determinant after
      acute myocardial infarction (AMI). ECG data have been used to measure infarct
      size, but conventional approaches use multiparametric algorithms that have
      limited clinical applicability. This study tested a novel ECG approach - based
      solely on Q wave area - for calculation of LV infarct size. METHODS: Serial 12
      lead ECGs were performed in AMI patients. Computerized software was used to
      quantify Q wave area (summed across surface ECG leads) and Selvester QRS-score
      components. ECG analysis was compared to the reference of myocardial infarct size
      quantified by delayed enhancement cardiac magnetic resonance. RESULTS: Overall,
      158 patients underwent ECG during early (4+/-0.4) and follow-up (29+/-5 days)
      post-AMI time points. Selvester QRS-score and Q wave area increased stepwise with
      LV infarct size (P<0.001). Whereas both methods manifested marked increases at a
      threshold of 10% LV infarction, magnitude was greater for Q wave area (>2.5-fold)
      than Selvester QRS-score (<two-fold). In receiver operating characteristic
      analysis, Q wave area (area under the curve=0.83-0.86) and Selvester QRS-score
      (0.82-0.87) manifested similar performance in relation to a 10% infarct cutoff.
      When Selvester QRS-score and Q wave area thresholds were selected to optimize
      sensitivity, both methods yielded similar negative predictive value (Q wave area:
      89-91%, Selvester QRS-score: 92-94%) although specificity was higher for Q wave
      area (44-45 vs. 17-25%; P<=0.01). CONCLUSION: Q wave area provides an index for
      stratification of LV infarct size that performs similarly to conventional ECG
      assessment via the Selvester QRS-score for exclusion of large infarction.

PMID- 24300168
TI  - Membrane-SPINE: a biochemical tool to identify protein-protein interactions of
      membrane proteins in vivo.
AB  - Membrane proteins are essential for cell viability and are therefore important
      therapeutic targets(1-3). Since they function in complexes(4), methods to
      identify and characterize their interactions are necessary(5). To this end, we
      developed the Membrane Strep-protein interaction experiment, called Membrane
      SPINE(6). This technique combines in vivo cross-linking using the reversible
      cross-linker formaldehyde with affinity purification of a Strep-tagged membrane
      bait protein. During the procedure, cross-linked prey proteins are co-purified
      with the membrane bait protein and subsequently separated by boiling. Hence, two
      major tasks can be executed when analyzing protein-protein interactions (PPIs) of
      membrane proteins using Membrane- SPINE: first, the confirmation of a proposed
      interaction partner by immunoblotting, and second, the identification of new
      interaction partners by mass spectrometry analysis. Moreover, even low affinity,
      transient PPIs are detectable by this technique. Finally, Membrane-SPINE is
      adaptable to almost any cell type, making it applicable as a powerful screening
      tool to identify PPIs of membrane proteins.

PMID- 24300169
TI  - Noninvasive measurement of smoking-associated N(3)-ethyladenine and N(7)
      ethylguanine in human salivary DNA by stable isotope dilution nanoflow liquid
      chromatography-nanospray ionization tandem mass spectrometry.
AB  - Evidence showed that ethylating agents are contained in cigarette smoke, which
      damage DNA producing ethylated DNA adducts, including N(3)-ethyladenine (3-EtAde)
      and N(7)-ethylguanine (7-EtGua). These two ethylpurines can be depurinated
      spontaneously and be repaired by enzymes and they have been detected in human
      urine. In this study, a highly specific and sensitive assay based on stable
      isotope dilution nanoflow liquid chromatography nanospray ionization tandem mass
      spectrometry (nanoLC-NSI/MS/MS) was used to measure 3-EtAde and 7-EtGua in human
      salivary DNA. These ethylpurines were released from DNA by neutral thermal
      hydrolysis and then enriched by a solid-phase extraction column before nanoLC
      NSI/MS/MS analysis. The detection limits (S/N>=3) of 3-EtA and 7-EtG were 15 fg
      (92 amol) and 10 fg (56 amol), respectively, injected on-column. The lower
      quantification limits of 3-EtAde and 7-EtGua were both 100 fg, i.e. 620 and 560
      amol, respectively, corresponding to 9.4 and 8.6 adducts in 10(9) normal
      nucleotides, respectively, starting with as little as 20 MUg of DNA isolated from
      an average of 3 mL of saliva. The mean (+/-SD) levels of 3-EtAde in 15 smokers
      and 15 nonsmokers were 12.6+/-7.0 and 9.7+/-5.3 in 10(8) normal nucleotides,
      respectively, while those of 7-EtGua were 14.1+/-8.2 and 3.8+/-2.8 in 10(8)
      normal nucleotides in smokers and nonsmokers, respectively. Levels of 7-EtGua,
      but not 3-EtAde, were statistically significantly higher in smokers than in
      nonsmokers (p<0.0001). Furthermore, salivary 7-EtGua levels are significantly
      correlated with the number of cigarettes smoked per day as well as with the
      smoking index. This highly specific and sensitive stable isotope dilution nanoLC
      NSI/MS/MS assay might be feasible in measuring 7-EtGua in human salivary DNA as a
      noninvasive biomarker for DNA damage induced by cigarette smoking.

PMID- 24300171
TI  - Indicine N-oxide binds to tubulin at a distinct site and inhibits the assembly of
      microtubules: a mechanism for its cytotoxic activity.
AB  - Indicine N-oxide, a pyrrolizidine alkaloid present in the plant Heliotropium
      indicum had shown promising cytotoxic activity in various tumor models. The
      compound exhibited severe toxicity to hepatocytes and bone marrow cells. The
      present work was aimed to evaluate the molecular mechanism of the toxicity of
      indicine N-oxide. We found that indicine N-oxide inhibited the proliferation of
      various cancer cell lines in a concentration dependent manner with IC50 ranging
      from 46 to 100 MUM. At the half maximal inhibitory concentration it blocked the
      cell cycle progression at mitosis without significantly altering the organization
      of the spindle and interphase microtubules. The toxicities of the compound at
      higher concentrations are attributed to its severe depolymerizing effect on both
      the interphase and spindle microtubules. Binding studies using purified goat
      brain tubulin indicated that indicine N-oxide binds to tubulin at a distinct site
      not shared by colchicine or taxol. It decreased the polymer mass of both purified
      tubulin and MAP-rich tubulin. It was found to induce cleavage of DNA using pUC18
      plasmid. The interactions of indicine N-oxide on DNA were also confirmed by
      computational analysis; which predicted its binding site at the minor groove of
      DNA. These studies bring to light that the toxicities of indicine N-oxide were
      due to its DNA damaging effects and depolymerization of microtubules.

PMID- 24300170
TI  - Fluoride promotes osteoblastic differentiation through canonical Wnt/beta-catenin
      signaling pathway.
AB  - Although fluoride is known to stimulate bone formation, the underlying mechanisms
      are not fully understood. Recent studies have implicated the Wnt/beta-catenin
      pathway as a major signaling cascade in bone biology. Our earlier studies
      highlighted a probable role of canonical Wnt pathway in bone formation of chronic
      fluoride-exposed rats, but the mechanism remains unclear. The current study
      determined the involvement of Wnt/beta-catenin signaling in fluoride-induced
      osteoblastic differentiation. Using primary rat osteoblasts, we demonstrated that
      fluoride significantly promoted osteoblasts proliferation and alkaline phosphate
      (ALP) expression as well as the mRNA expression levels of bone differentiation
      markers, including type I collagen (COL1A1), ALP and osteonectin. We further
      found fluoride induced phosphorylations at serine 473 of Akt and serine 9 of
      glycogen synthase kinase-3beta (GSK3beta), which resulted in GSK-3beta inhibition
      and subsequently the nuclear accumulation of the beta-catenin, as shown by
      Western blot and immunofluorescence analysis. Moreover, fluoride also induced the
      expression of Wnt-targeted gene runt-related transcription factor 2 (Runx2).
      Importantly, the positive effect of fluoride on ALP activity and mRNA expressions
      of COL1A1, ALP, osteonection and Runx2 was abolished by DKK-1, a blocker of the
      Wnt/beta-catenin receptor. Taken together, these findings suggest that fluoride
      promotes osteoblastic differentiation through Akt- and GSK-3beta-dependent
      activation of Wnt/beta-catenin signaling pathway in primary rat osteoblasts. Our
      findings provide novel insights into the mechanisms of action of fluoride in
      osteoblastogenesis. 

PMID- 24300172
TI  - NQO1 involves in the imine bond reduction of sanguinarine and recombinant adeno
      associated virus mediated NQO1 overexpression decreases sanguinarine-induced
      cytotoxicity in rat BRL cells.
AB  - Although sanguinarine (SANG) can be transformed to dihydrosanguinarine (DHSA) in
      human and animals, the enzyme involved in the imine bond reduction of SANG is
      still unknown. In this study, we found that rat NAD(P)H: quinone oxidoreductase 1
      expressed by prokaryotic system can transform SANG to DHSA in an NADPH dependent
      manner. We also found out that there was more DHSA in rAAV-NQO1 infected than
      rAAV-CYP1A1 and rAAV-control infected BRL cells. SANG decreased rat BRL cell
      proliferation and augmented cell apoptosis in a time and dose dependent manner.
      However, the influence of DHSA to BRL cells is not significant difference than
      SANG. SANG-induced apoptosis was correlated with the up-regulation of Bax/Bcl2
      ratio and the down-regulation of Bcl2. SANG can also dose dependently down
      regulate NQO1 expression, but CYP1A1 expression was a little up regulated. Since
      CYP1A1 involving in SANG oxidative reactions and NQO1 involving in the transform
      of SANG to DHSA, we hypothesized that up regulation of NQO1 could reduce SANG
      cytotoxicity and up regulation of CYP1A1 could increase SANG cytotoxitity. Our
      further study showed that recombinant adeno-associated virus (rAAV) mediated
      overexpression of NQO1 significantly increased cell proliferation and decreased
      Bax/Bcl2 ratio, apoptosis, and cytotoxicity, whereas rAAV mediated CYP1A1
      overexpression had opposite effects. These data illustrated that NQO1 involved in
      the imine bond reduction of sanguinarine and this was a less toxic metabolizing
      pathway than CYP1A1-metabolizing pathway.

PMID- 24300174
TI  - Functional analysis of the larval feeding circuit in Drosophila.
AB  - The serotonergic feeding circuit in Drosophila melanogaster larvae can be used to
      investigate neuronal substrates of critical importance during the development of
      the circuit. Using the functional output of the circuit, feeding, changes in the
      neuronal architecture of the stomatogastric system can be visualized. Feeding
      behavior can be recorded by observing the rate of retraction of the mouth hooks,
      which receive innervation from the brain. Locomotor behavior is used as a
      physiological control for feeding, since larvae use their mouth hooks to traverse
      across an agar substrate. Changes in feeding behavior can be correlated with the
      axonal architecture of the neurites innervating the gut. Using
      immunohistochemistry it is possible to visualize and quantitate these changes.
      Improper handling of the larvae during behavior paradigms can alter data as they
      are very sensitive to manipulations. Proper imaging of the neurite architecture
      innervating the gut is critical for precise quantitation of number and size of
      varicosities as well as the extent of branch nodes. Analysis of most circuits
      allow only for visualization of neurite architecture or behavioral effects;
      however, this model allows one to correlate the functional output of the circuit
      with the impairments in neuronal architecture. 

PMID- 24300173
TI  - Early chronic low-level lead exposure produces glomerular hypertrophy in young
      C57BL/6J mice.
AB  - Early chronic lead exposure continues to pose serious health risks for children,
      particularly those living in lower socioeconomic environments. This study
      examined effects on developing glomeruli in young C57BL/6J mice exposed to low
      (30 ppm), higher (330 ppm) or no lead via dams' drinking water from birth to
      sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19
      (0.70) MUg/dL] had an increase in glomerular volume but no change in podocyte
      number compared to control mice [0.03 (0.01) MUg/dL]. Higher-level lead exposed
      mice [14.68 (2.74) MUg/dL] had no change in either glomerular volume or podocyte
      number. The increase in glomerular volume was explained by increases in
      glomerular capillary and mesangial volumes with no change in podocyte volume.
      Early chronic lead exposure yielding very low blood lead levels alters glomerular
      development in pre-adolescent animals.

PMID- 24300175
TI  - Transmitting plant viruses using whiteflies.
AB  - Whiteflies, Hemiptera: Aleyrodidae, Bemisia tabaci, a complex of morphologically
      indistinquishable species(5), are vectors of many plant viruses. Several genera
      of these whitefly-transmitted plant viruses (Begomovirus, Carlavirus, Crinivirus,
      Ipomovirus, Torradovirus) include several hundred species of emerging and
      economically significant pathogens of important food and fiber crops (reviewed
      by(9,10,16)). These viruses do not replicate in their vector but nevertheless are
      moved readily from plant to plant by the adult whitefly by various means
      (reviewed by(2,6,7,9,10,11,17)). For most of these viruses whitefly feeding is
      required for acquisition and inoculation, while for others only probing is
      required. Many of these viruses are unable or cannot be easily transmitted by
      other means. Therefore maintenance of virus cultures, biological and molecular
      characterization (identification of host range and symptoms)(3,13),
      ecology(2,12), require that the viruses be transmitted to experimental hosts
      using the whitefly vector. In addition the development of new approaches to
      management, such as evaluation of new chemicals(14) or compounds(15), new
      cultural approaches(1,4,19), or the selection and development of resistant
      cultivars(7,8,18), requires the use of whiteflies for virus transmission. The use
      of whitefly transmission of plant viruses for the selection and development of
      resistant cultivars in breeding programs is particularly challenging(7).
      Effective selection and screening for resistance employs large numbers of plants
      and there is a need for 100% of the plants to be inoculated in order to find the
      few genotypes which possess resistance genes. These studies use very large
      numbers of viruliferous whiteflies, often several times per year. Whitefly
      maintenance described here can generate hundreds or thousands of adult whiteflies
      on plants each week, year round, without the contamination of other plant
      viruses. Plants free of both whiteflies and virus must be produced to introduce
      into the whitefly colony each week. Whitefly cultures must be kept free of
      whitefly pathogens, parasites, and parasitoids that can reduce whitefly
      populations and/or reduce the transmission efficiency of the virus. Colonies
      produced in the manner described can be quickly scaled to increase or decrease
      population numbers as needed, and can be adjusted to accommodate the feeding
      preferences of the whitefly based on the plant host of the virus. There are two
      basic types of whitefly colonies that can be maintained: a nonviruliferous and a
      viruliferous whitefly colony. The nonviruliferous colony is composed of
      whiteflies reared on virus-free plants and allows the weekly availability of
      whiteflies which can be used to transmit viruses from different cultures. The
      viruliferous whitefly colony, composed of whiteflies reared on virus-infected
      plants, allows weekly availability of whiteflies which have acquired the virus
      thus omitting one step in the virus transmission process. 

PMID- 24300176
TI  - Longitudinal follow-up of the relationship between dietary intake and growth and
      development in the Lifeways cross-generation cohort study 2001-2013.
AB  - In this paper we will review evidence on the early life and familial influences
      on childhood growth and development, with particular reference to the Lifeways
      cross-generation cohort study in the Republic of Ireland. The Lifeways cross
      generation cohort study was established in 2001-2013 through two maternity
      hospitals in the Republic of Ireland and was one of many new cohort studies
      established worldwide in the millennium period. Mothers were recruited at first
      booking visit, completing a self-administered questionnaire, which included a 147
      item semi-quantitative FFQ. Longitudinal follow-up is ongoing in 2013, with
      linkage data to hospital and general practice records and examination of children
      when aged 5 and 9 years. The study is one of very few containing data on
      grandparents of both lineages with at least one grandparent recruited at
      baseline. There have been consistent associations between parental and
      grandparental health status characteristics and children's outcomes, including
      infant birth-weight, BMI when child was aged 5 years and childhood wheeze or
      asthma when child was aged 3 and aged 5 years. In conclusion, empirical evidence
      to date shows consistent familial and cross-generational patterns, particularly
      in the maternal line. 

PMID- 24300177
TI  - Trojan microparticles for drug delivery.
AB  - During the last decade, the US Food and Drug Administration (FDA) have regulated
      a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and
      tobacco) which may utilize micro and nanotechnology or contain nanomaterials.
      Nanotechnology allows scientists to create, explore, and manipulate materials in
      nano-regime. Such materials have chemical, physical, and biological properties
      that are quite different from their bulk counterparts. For pharmaceutical
      applications and in order to improve their administration (oral, pulmonary and
      dermal), the nanocarriers can be spread into microparticles. These supramolecular
      associations can also modulate the kinetic releases of drugs entrapped in the
      nanoparticles. Different strategies to produce these hybrid particles and to
      optimize the release kinetics of encapsulated drugs are discussed in this review.

PMID- 24300178
TI  - Tissue engineered human skin equivalents.
AB  - Human skin not only serves as an important barrier against the penetration of
      exogenous substances into the body, but also provides a potential avenue for the
      transport of functional active drugs/reagents/ingredients into the skin (topical
      delivery) and/or the body (transdermal delivery). In the past three decades,
      research and development in human skin equivalents have advanced in parallel with
      those in tissue engineering and regenerative medicine. The human skin equivalents
      are used commercially as clinical skin substitutes and as models for permeation
      and toxicity screening. Several academic laboratories have developed their own
      human skin equivalent models and applied these models for studying skin
      permeation, corrosivity and irritation, compound toxicity, biochemistry,
      metabolism and cellular pharmacology. Various aspects of the state of the art of
      human skin equivalents are reviewed and discussed. 

PMID- 24300179
TI  - Novel experimental and clinical therapeutic uses of low-molecular-weight
      heparin/protamine microparticles.
AB  - Low-molecular-weight heparin/protamine microparticles (LMW-H/P MPs) were produced
      as a carrier for heparin-binding growth factors (GFs) and for various adhesive
      cells. A mixture of low-molecular-weight heparin (MW: approximately 5000 Da, 6.4
      mg/mL) and protamine (MW: approximately 3000 Da, 10 mg/mL) at a ratio of 7:3
      (vol:vol) yields a dispersion of microparticles (0.5-3 um in diameter). LMW-H/P
      MPs immobilize, control the release and protect the activity of GFs. LMW-H/P MPs
      can also bind to cell surfaces, causing these cells to interact with the LMW-H/P
      MPs, inducing cells/MPs-aggregate formation and substantially promoting cellular
      viability. Furthermore, LMW-H/P MPs can efficiently bind to tissue culture plates
      and retain the binding of important GFs, such as fibroblast growth factor (FGF)
      2. The LMW-H/P MPs-coated matrix with various GFs or cytokines may provide novel
      biomaterials that can control cellular activity such as growth and
      differentiation. Thus, LMW-H/P MPs are an excellent carrier for GFs and various
      cells and are an efficient coating matrix for cell cultures. 

PMID- 24300180
TI  - Recrystallization of commercial carbamazepine samples-a strategy to control
      dissolution variability.
AB  - Physical properties of commercial carbamazepine (CBZ) samples can significantly
      influence drug release and thereby jeopardize bioequivalence of the final dosage
      form. The aim of this study was to reduce variability in commercial CBZ samples
      by recrystallization. CBZ samples of four different suppliers were recrystallized
      in ethanol solution containing 1% polyvinylpyrrolidone (PVP). CBZ samples were
      analyzed by disk intrinsic dissolution rate (DIDR), X-ray powder diffraction
      (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy
      (SEM). Recrystallized CBZ samples showed strongly reduced variability in DIDR
      compared to the untreated CBZ samples. Moreover, transformation process to CBZ
      dihydrate was inhibited; no dihydrate crystals were visible on compact surfaces
      after 8 h intrinsic dissolution measurement. Recrystallized CBZ samples showed no
      change in polymorphic form, however, particle size and shape was inhomogenous. In
      binary mixtures with microcrystalline cellulose, recrystallized CBZ samples again
      showed difference in drug release. This difference was associated with the
      inhomogenous particle size in the recrystallized CBZ samples. The results show
      that a controlled grinding step is required after recrystallization. We suggest
      the recrystallization in presence of 1% PVP followed by a controlled grinding
      step as a strategy to reduce dissolution variability in commercial CBZ samples. 

PMID- 24300182
TI  - Atomic pairwise distribution function analysis of the amorphous phase prepared by
      different manufacturing routes.
AB  - Amlodipine besilate, a calcium channel antagonist, exists in several solid forms.
      Processing of anhydrate and dihydrate forms of this drug may lead to solid state
      changes, and is therefore the focus of this study. Milling was performed for the
      anhydrate form, whereas the dihydrate form was subjected to quench cooling
      thereby creating an amorphous form of the drug from both starting materials. The
      milled and quench cooled samples were, together with the crystalline starting
      materials, analyzed with X-ray powder diffraction (XRPD), Raman spectroscopy and
      atomic pair-wise distribution function (PDF) analysis of the XRPD pattern. When
      compared to XRPD and Raman spectroscopy, the PDF analysis was superior in
      displaying the difference between the amorphous samples prepared by milling and
      quench cooling approaches of the two starting materials. 

PMID- 24300181
TI  - Structure Enhancement Relationship of Chemical Penetration Enhancers in Drug
      Transport across the Stratum Corneum.
AB  - The stratum corneum is a major barrier of drug penetration across the skin in
      transdermal delivery. For effective transdermal drug delivery, skin penetration
      enhancers are used to overcome this barrier. In the past decades, a number of
      research studies were conducted to understand the mechanisms of skin penetration
      enhancers and to develop a structure enhancement relationship. Such understanding
      allows effective prediction of the effects of skin penetration enhancers, assists
      topical and transdermal formulation development, and avoids extensive enhancer
      screening in the transdermal delivery industry. In the past two decades, several
      hypotheses on chemical enhancer-induced penetration enhancement for transport
      across the skin lipoidal pathway have been examined based on a systematic
      approach. Particularly, a hypothesis that skin penetration enhancement is
      directly related to the concentration of the enhancers in the stratum corneum
      lipid domain was examined. A direct relationship between skin penetration
      enhancer potency (based on enhancer aqueous concentration in the diffusion cell
      chamber) and enhancer n-octanol-water partition coefficient was also established.
      The nature of the microenvironment of the enhancer site of action in the stratum
      corneum lipid domain was found to be mimicked by n-octanol. The present paper
      reviews the work related to these hypotheses and the relationships between skin
      penetration enhancement and enhancer concentration in the drug delivery media and
      stratum corneum lipids. 

PMID- 24300183
TI  - Lecithin-linker microemulsion gelatin gels for extended drug delivery.
AB  - This article introduces the formulation of alcohol-free, lecithin microemulsion
      based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil,
      water, lecithin and hydrophilic and lipophilic additives (linkers) on the
      rheological properties and appearance of these gels was systematically explored
      using ternary phase diagrams. Clear MBGs were obtained in regions of single phase
      microemulsions (MUEs) at room temperature. Increasing the water content in the
      formulation increased the elastic modulus of the gels, while increasing the oil
      content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric
      glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly
      at high temperatures. In contrast to anionic (AOT) MUEs, the results suggest that
      in lecithin (nonionic) MUEs, the introduction of gelatin "dehydrates" the MUE.
      Finally, when the transdermal transport of lidocaine formulated in the parent MUE
      and the resulting MBG were compared, only a minor retardation in the loading and
      release of lidocaine was observed. 

PMID- 24300184
TI  - Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel Carriers for DNA,
      shRNA and siRNA.
AB  - Gene, short hairpin RNA (shRNA) and small interfering RNA (siRNA) delivery can be
      particularly used for the treatment of diseases by the entry of genetic materials
      mammalian cells either to express new proteins or to suppress the expression of
      proteins, respectively. Polyamidoamine (PAMAM) StarburstTM dendrimers are used as
      non-viral vectors (carriers) for gene, shRNA and siRNA delivery. Recently,
      multifunctional PAMAM dendrimers can be used for the wide range of biomedical
      applications including intracellular delivery of genes and nucleic acid drugs. In
      this context, this review paper provides the recent findings on PAMAM dendrimer
      conjugates with cyclodextrins (CyDs) for gene, shRNA and siRNA delivery. 

PMID- 24300185
TI  - Probiotic encapsulation technology: from microencapsulation to release into the
      gut.
AB  - Probiotic encapsulation technology (PET) has the potential to protect
      microorgansisms and to deliver them into the gut. Because of the promising
      preclinical and clinical results, probiotics have been incorporated into a range
      of products. However, there are still many challenges to overcome with respect to
      the microencapsulation process and the conditions prevailing in the gut. This
      paper reviews the methodological approach of probiotics encapsulation including
      biomaterials selection, choice of appropriate technology, in vitro release
      studies of encapsulated probiotics, and highlights the challenges to be overcome
      in this area. 

PMID- 24300186
TI  - In Situ Focused Beam Reflectance Measurement (FBRM), Attenuated Total Reflectance
      Fourier Transform Infrared (ATR-FTIR) and Raman Characterization of the
      Polymorphic Transformation of Carbamazepine.
AB  - The objective of this work was to study the polymorphic transformation of
      carbamazepine from Form II to Form III in 1-propanol during seeded isothermal
      batch crystallization. First, the pure Form II and Form III were obtained and
      characterized. Then their solubilities and metastable zone limits were measured
      by in-situ attenuated total reflectance Fourier transform infrared (ATR-FTIR)
      spectroscopy and focused beam reflectance measurement (FBRM). A transition
      temperature at about 34.2  degrees C was deduced suggesting the enantiotropic
      nature of this compound over the studied temperature range. To quantify the
      polymorph ratio during the transformation process, a new in-situ quantitative
      method was developed to measure the fraction of Form II by Raman spectroscopy.
      Successful tracking of the nucleation of the stable form and the transformation
      from Form II to Form III during isothermal crystallization was achieved by Raman
      spectroscopy and FBRM. The results from these three in-situ techniques, FBRM,
      FTIR and Raman were consistent with each other. The results showed a strong
      dependency on the amount of seeds added during isothermal crystallization. 

PMID- 24300187
TI  - Preparation and characterization of amino acids-based trimethoprim salts.
AB  - Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents
      the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the
      depletion of the latter and leading to bacterial death. Oral bioavailability of
      TMP is hindered by both its low solubility and low permeability. This study aims
      to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic
      acid as counter ions in order to improve solubility and dissolution. TMP salts
      were prepared by lyophilisation and characterized using FT-IR spectroscopy,
      proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry
      (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts
      with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility.
      Investigation of the microbiological activity of the prepared salts against TMP
      sensitive Escherichia coli showed that the new salts not only retained
      antibacterial activity but also exhibited higher zone of inhibition which was
      attributed to improved physicochemical characters such as higher solubility and
      dissolution. The results are an important finding that could potentially impact
      on faster onset of antibacterial activity and reduced therapeutic dose when
      administered to patients. Studies are underway investigating the effect of ion
      pairing TMP with amino acids on the permeability profile of the drug. 

PMID- 24300188
TI  - Ocular drug delivery for glaucoma management.
AB  - Current glaucoma management modalities are hindered by low patient compliance and
      adherence. This can be due to highly complex treatment strategies or poor patient
      understanding. Treatments focus on the management or reduction of intraocular
      pressure. This is most commonly done through the use of daily topical eye drops.
      Unfortunately, despite effective therapies, glaucoma continues to progress,
      possibly due to patients not adhering to their treatments. In order to mitigate
      these patient compliance issues, many sustained release treatments are being
      researched and are entering the clinic. Conjunctival, subconjunctival, and
      intravitreal inserts, punctal plugs, and drug depots are currently in clinical
      development. Each delivery system has hurdles, yet shows promise and could
      potentially mitigate the current problems associated with poor patient
      compliance. 

PMID- 24300189
TI  - Evaluation of tissue interactions with mechanical elements of a transscleral drug
      delivery device.
AB  - The goal of this work was to evaluate tissue-device interactions due to
      implantation of a mechanically operated drug delivery system onto the posterior
      sclera. Two test devices were designed and fabricated to model elements of the
      drug delivery device-one containing a free-spinning ball bearing and the other
      encasing two articulating gears. Openings in the base of test devices modeled
      ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene)
      (PTFE) membranes were attached to half of the gear devices to minimize tissue
      ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10
      weeks. Tissue-device interactions were evaluated histologically and mechanically
      after removal to determine effects on device function and changes in surrounding
      tissue. Test devices were generally well-tolerated during residence in the
      animal. All devices encouraged fibrous tissue formation between the sclera and
      the device, fibrous tissue encapsulation and invasion around the device, and
      inflammation of the conjunctiva. Gear devices encouraged significantly greater
      inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes
      prevented tissue invasion through the covered drug ports, though tissue migrated
      in through other smaller openings. The torque required to turn the mechanical
      elements increased over 1000 times for gear devices, but only on the order of 100
      times for membrane-covered gear devices and less than 100 times for ball bearing
      devices. Maintaining a lower device profile, minimizing microscale motion on the
      eye surface and covering drug ports with a porous membrane may minimize
      inflammation, decreasing the risk of damage to surrounding tissues and minimizing
      disruption of device operation. 

PMID- 24300191
TI  - Ophthalmic drug delivery in glaucoma-a review.
AB  - Glaucoma is a progressive optic neuropathy and medical therapy is the initial
      option for the treatment of this potentially blinding condition. Topical
      instillation of eye drops from the bottle is the most common glaucoma drug
      delivery form. Due to limited permeability of anterior ocular surface, natural
      clearance and drainage, eye drops contain large amounts of inactive ingredients.
      Effective penetration enhancers are known as irritants causing ocular discomfort.
      Although drug efficacy is determined by active ingredients, inactive agents can
      affect tolerance and can result in conjunctival irritation and hyperemia and
      influence patients' adherence and quality of life. 

PMID- 24300190
TI  - Delivery of intraocular triamcinolone acetonide in the treatment of macular
      edema.
AB  - Macular edema (ME) is one of the eventual outcomes of various intraocular and
      systemic pathologies. The pathogenesis for ME is not yet entirely understood;
      however, some of the common risk factors for its development have been
      identified. While this investigation will not discuss the numerous etiologies of
      ME in detail, it appraises the two most widely studied delivery modalities of
      intraocular corticosteroids in the treatment of ME-intravitreal injection (IVI)
      and sub-Tenon's infusion (STI). A thorough review of the medical literature was
      conducted to identify the efficacy and safety of IVI and STI, specifically for
      the administration of triamcinolone acetonide (TA), in the setting of ME in an
      attempt to elucidate a preferred steroid delivery modality for treatment of ME. 

PMID- 24300192
TI  - Production of large numbers of size-controlled tumor spheroids using microwell
      plates.
AB  - Tumor spheroids are increasingly recognized as an important in vitro model for
      the behavior of tumor cells in three dimensions. More physiologically relevant
      than conventional adherent-sheet cultures, they more accurately recapitulate the
      complexity and interactions present in real tumors. In order to harness this
      model to better assess tumor biology, or the efficacy of novel therapeutic
      agents, it is necessary to be able to generate spheroids reproducibly, in a
      controlled manner and in significant numbers. The AggreWell system consists of a
      high-density array of pyramid-shaped microwells, into which a suspension of
      single cells is centrifuged. The numbers of cells clustering at the bottom of
      each microwell, and the number and ratio of distinct cell types involved depend
      only on the properties of the suspension introduced by the experimenter. Thus, we
      are able to generate tumor spheroids of arbitrary size and composition without
      needing to modify the underlying platform technology. The hundreds of microwells
      per square centimeter of culture surface area in turn ensure that extremely high
      production levels may be attained via a straightforward, nonlabor-intensive
      process. We therefore expect that this protocol will be broadly useful to
      researchers in the tumor spheroid field. 

PMID- 24300193
TI  - Effect of Cd, Zn and Hg complexes of barbituric acid and thiouracil on rat brain
      monoamine oxidase-B (in vitro).
AB  - Metal pyrimidine complexes (MPCs) including cadmium-barbiturate (Cd-BA), zinc
      barbiturate (Zn-BA), cadmium-thiouracil (Cd-TU) and mercury-thiouracil (Hg-TU)
      were prepared and their analysis was carried out. These MPCs were evaluated as
      monoamine oxidase-B (MAO-B) inhibitors. Rat brain MAO-B was inhibited (in vitro)
      by Cd-BA, Zn-BA, Cd-TU and Hg-TU complexes. The inhibition of MAO-B by these
      complexes was time and concentration dependent. The values of IC50 of Zn-BA, Cd
      BA, Hg-TU and Cd-TU were 10.2, 15.8, 16.2 and 20.4 nM, respectively. The effect
      of different substrate concentrations in the absence and in the presence of MPCs
      was determined. Lineweaver-Burk plots were plotted and the values of apparent
      Michaelis constant (Km), maximum velocity (Vmax), the dissociation constant of
      enzyme inhibitor complex (Ki) and the percent of inhibition (i%) were calculated.
      The data showed that the inhibition of MAO-B by all studied MPCs was the non
      competitive type. The sequence of inhibition zone was: Zn-BA>Cd-BA and Hg-TU>Cd
      TU affected by the chemistry of both the metal and the ligand. Otherwise, the
      results of the present study showed that the inhibition of MAO-B by all MPCs was
      fully reversible. The data showed that the presence of Cd-BA, Zn-BA, Cd-TU and Hg
      TU complexes changed the optimum temperature and pH of MAO-B. 

PMID- 24300194
TI  - Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.
AB  - The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great
      practical and research interest because of its pronounced, widespread
      physiological effects, primarily antimicrobial and anti-inflammatory, arising
      from its ability to interact with proteins and DNA. Although CHE was originally
      shown to possess anti-inflammatory properties, its effects on acute gastric ulcer
      have not been previously explored. The aim of the present study is to evaluate
      the protective effect of CHE on ethanol induced gastric ulcer in mice.
      Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol
      ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion
      was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO)
      activities, macroscopic and histopathological examinations. CHE significantly
      reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and
      histological score in a dose-dependent manner. In addition, CHE also
      significantly inhibited nitric oxide (NO) concentration, pro-inflammatory
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) level in serum
      and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose
      dependent manner. In addition, immunohistochemical analysis revealed that CHE
      markedly attenuated the overexpression of nuclear factor-kappaB in gastric mucosa
      of mice. It was concluded that CHE represents a potential therapeutic option to
      reduce the risk of gastric ulceration. In addition, acute toxicity study revealed
      no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest
      that the gastroprotective activity of CHE might contribute in adjusting the
      inflammatory cytokine by regulating the NF-kappaB signalling pathway. 

PMID- 24300195
TI  - A novel compound RY10-4 induces apoptosis and inhibits invasion via inhibiting
      STAT3 through ERK-, p38-dependent pathways in human lung adenocarcinoma A549
      cells.
AB  - Previous reports suggested that protoapigenone showed remarkable antitumor
      activities against a broad spectrum of human cancer cell lines, but had no effect
      on human lung adenocarcinoma A549 cell. The lack of effective remedies had
      necessitated the application of new therapeutic scheme. A novel compound RY10-4
      which has the similar structure close to protoapigenone showed better antitumor
      activity. Treatment with RY10-4 inhibited the expression of pro-caspase-3, pro
      caspase-9, Bcl-2 as well as phosphorylation of signal transducer and activator of
      transcription-3 (p-STAT3). It also reduced the expressions of matrix
      metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and increases the
      expressions of reversion-inducing cysteine-rich protein with kazal motifs (RECK),
      as well as tissue inhibitor of metalloproteinase (TIMP) via inhibiting STAT3 by
      activating the mitogen-activated protein (MAP) kinases (the c-Jun N-terminal
      kinase (JNK), the p38 and extracellular signal-regulated kinase (ERK)) in A549
      cells treated with RY10-4. Moreover, the cytotoxic effect of RY10-4 was induction
      of apoptosis in A549 cells by enhancing production of reactive oxygen species
      (ROS). Taken together, the observations suggested that RY10-4 had affected Bcl-2
      family members, caspases, MMPs, TIMPs expressions and ROS production via
      inhibiting STAT3 activities through ERK and p38 pathways in A549 cells. 

PMID- 24300196
TI  - Scleral contact lenses for visual rehabilitation after penetrating keratoplasty:
      long term outcomes.
AB  - PURPOSE: To evaluate the success rate of highly gas permeable scleral contact
      lenses (SCL) for visual rehabilitation after penetrating keratoplasty (PK), over
      a period of up to 9 years. METHODS: A total database of 31 consecutive patient
      fitted with SCL between January 2004 and December 2009 was retrospectively
      reviewed. Demographic data, etiology prior to lens fitting, visual outcomes,
      follow up time and complications were analyzed. RESULTS: All eyes were fitted due
      to inadequate spectacle-corrected vision after successful penetrating
      keratoplasty or failure of other contact lens modalities. Out of 31 patients
      fitted, 28 (33 eyes) continue to wear SCL for periods between 0.5 and 8.8 years.
      The mean duration of follow-up after contact lens fitting was 5.2 +/- 2.2 years.
      The mean age of corneal graft was 17.6 +/- 11.4 years (range 4.3-42), and the
      mean interval between PK and initial contact lens fitting was 12.2 +/- 10.7 years
      (range 0.7-36.0). The average steepest keratometry of our cohort was 55.0 +/- 7.5
      diopter (D) and the refractive astigmatism was 8.0 +/- 4.4 D. The mean contact
      lens corrected visual acuity (BCVAcl) was 0.78 +/- 0.25 (range 0.3-1.2). Twenty
      three (82%) patients achieved a functional vision of 0.5 or more. During the
      studied period, ten (30.0%) eyes presented at least one graft rejection episode
      and two eyes (6%) had an episode of microbial keratitis. Corneal transplants of
      20 years or more show a higher rate of refits due to ectasia recurrence.
      CONCLUSIONS: Scleral lenses should be considered as lens of choice in eyes with
      complex corneal geometry, as besides visual rehabilitation, their use may delay
      or prevent further surgical involvement.

PMID- 24300197
TI  - [Proportion and prevention of venous thromboembolism among hospitalized patients
      with acute exacerbation of chronic obstructive pulmonary disease in Beijing].
AB  - OBJECTIVE: To explore the proportion and prevention status of venous
      thromboembolism (VTE) among hospitalized patients with acute exacerbation of
      chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: Based on a
      multi-center retrospective study, a total of 636 hospitalized AECOPD patients
      from 17 class 2/3 hospitals in Beijing were examined from September 1, 2011 to
      March 31, 2012. They fulfilled one of the following criteria: respiratory failure
      type II, on invasive or non-invasive mechanical ventilation, hospitalization for
      pulmonary infection, bedridden duration >= 3 days and congestive heart failure.
      All investigators received standardized training and used a standardized
      questionnaire to collect data on VTE risk factors, the diagnosis of VTE and the
      utilization of VTE prophylaxis. According to Caprini score, they were categorized
      into 3 groups of lower risk (Caprini score <= 3), moderate risk (Caprini score 4
      6) and high risk ( >= 7) to compare the intergroup differences in the VTE
      proportion and the utilization of VTE prophylaxis. RESULTS: A total of 636
      patients were assessed. There were 416 males and 220 females with a mean (SD) age
      of 74.9 +/- 9.3 years. Among them, 133 patients received lower extremity venous
      ultrasonic examination and 92 were diagnosed with deep venous thrombosis (DVT)
      including 2 patients with pulmonary thromboembolism (PTE). Thus the overall
      incidence of VTE was 14.5% (92/636) and increased with age (Ptrend = 0.044). The
      proportion of VTE in asymptomatic patients was higher in those symptomatic ones
      (21.1% vs 8.0%, P = 0.000). And it was the highest in high risk group, followed
      by lower risk and moderate risk groups at 17.9% (14/78), 16.0% (26/163) and 13.2%
      (52/395) respectively, There was no statistical significance (P = 0.450 for group
      difference, Ptrend = 0.946). Among 544 patients without VTE, only 19.1% (104/544)
      employed the pharmacologic and/or mechanical methods for preventing VTE. The
      prevention proportion gradually increased with rising Caprini score, i.e. 17.5%,
      18.4% and 26.6% for lower, moderate and higher risk group respectively. There was
      no statistical significance (P = 0.266 for group difference, Ptrend = 0.201).
      CONCLUSIONS: The proportion of VTE is relatively higher. However, the preventive
      methods are significantly underutilized among hospitalized AECOPD patients in
      Beijing.

PMID- 24300198
TI  - [Curative effects on standardized management of community patients with coronary
      heart disease complicated with chronic heart failure].
AB  - OBJECTIVE: To explore the effects on the standardized management of patients with
      coronary atherosclerotic heart disease complicated with chronic heart failure.
      METHODS: A total of 823 patients discharged from our department were randomly
      enrolled. Among 734 patients with follow-up consents, they were divided into
      management and control groups (n = 440, 294). The management group received
      standardized out-of-hospital management, regular health education and follow-ups
      of telephone and outpatient visits. RESULTS: Compared with the control group, the
      management group had lower rates of all-cause mortality, cardiac death and
      readmission due to cardiovascular events (CVE) declining by 26.5%, 32.2% and
      57.0% respectively. Over a 4-year period, the annular survival rate of management
      group was 92%, 85%, 83% and 82% while that of control group 95%, 89%, 82% and 75%
      respectively. Patient compliance of digoxin and diuretics in the control group
      was inferior to that in the management group. CONCLUSION: Through standardized
      out-of-hospital management, the patients with coronary atherosclerotic heart
      disease plus chronic heart failure may achieve significant benefits through
      reducing the rates of all-cause mortality, cardiac death and readmission due to
      CVE and improving survival rate.

PMID- 24300199
TI  - [Ultrafiltration versus intravenous diuretics in decompensated heart failure: a
      meta-analysis of randomized controlled trials].
AB  - OBJECTIVE: To explore whether ultrafiltration is superior to intravenous
      diuretics in ameliorating fluid overload and preserving renal functions in
      decompensated heart failure patients. METHODS: By searching in Pubmed, Cochrane
      Library, Embase, Springer, WanFang, CQVIP, CNKI and CBM database as well as
      related Chinese journals, qualified randomized controlled trials (RCTs) were
      included for meta-analysis by Revman 5.0 and STATA 10.0. RESULTS: Six RCTs were
      included with 241 patients in ultrafiltration group and 240 patients in
      intravenous diuretics group. Pooled analyses demonstrated ultrafiltration was
      superior to intravenous diuretics in the aspects of weight loss (WMD = 1.44 kg,
      95%CI:0.33-2.55 kg, P = 0.01) and fluid removal (WMD = 1.23 kg, 95%CI:0.63-1.82
      kg, P < 0.01) while no significant difference was observed in serum creatinine
      level (WMD = -5.70 umol/L, 95%CI: -35.02-23.61 umol/L, P = 0.70), serum
      creatinine change from baseline (WMD = 4.74 umol/L, 95%CI:-13.72-23.20 umol/L, P
      = 0.61), mortality (RR = 1.09, 95%CI: 0.69-1.70, P = 0.72) or rehospitalization
      (RR = 0.92, 95%CI:0.53-1.61, P = 0.78). CONCLUSIONS: For decompensated heart
      failure patients, ultrafiltration is superior to intravenous diuretics in
      mitigating fluid overload. No intergroup difference was observed in renal
      function preservation, mortality or rehospitalization.

PMID- 24300200
TI  - [In vitro studies of 2 um laser treatment of benign prostatic hyperplasia].
AB  - OBJECTIVE: To compare the speed of vaporization of human prostatic tissue with
      benign prostatic hyperplasia (BPH) and depth of tissue damage using 70 and 120 W
      2 um laser devices. METHODS: Fresh prostatic tissue specimens were obtained from
      5 patients by open prostatectomy and divided into separate groups (70 and 120 W)
      based on the energy of laser output (70 and 120 W respectively). Trials were
      performed in acryl basin containing 0.9% saline at 37  degrees C. And then each
      prostate gland in vitro was vaporizated similarly as routine transurethral 2 um
      laser vaporesection. 70 W and 120 W power were applied for prostatic
      vaporesection. The 2 um laser vaporization proportion and vaporesection speed
      were calculated postoperatively. Prostatic tissue was embedded for histological
      evaluation. After hematoxylin and eosin (H & E) staining and nicotinamide adenine
      dinucleotide-reduced (NADH) measurement, depth of coagulation zone and necrotic
      tissue layer were measured. The results of prostatic tissue between two groups
      were compared. RESULTS: With increasing output power, the speed (mean +/- SD) of
      vaporesection of human prostatic tissue increased from (5.21 +/- 0.66) g/5 min at
      70 W to (10.84 +/- 1.23) g/5 min at 120 W. Significant differences existed in the
      speed of vaporesection, resection and vaporization between 120 W and 70 W devices
      (P = 0.000). The proportion of vaporization mode was 81% at 70 W and 87% at 120 W
      during prostatic vaporesection. There was a stable penetration/coagulation depth
      with increasing power output for (0.98 +/- 0.13)/(0.30 +/- 0.09) mm at 70 W and
      (0.99 +/- 0.12)/(0.31 +/- 0.08) mm at 120 W. There were no significant
      differences in penetration and coagulation depth between 120 W and 70 W (P >
      0.05). CONCLUSIONS: Both 120 and 70 W 2 um Laser devices yield excellent
      performance and security in vaporizated human prostate tissue. The 120 W 2 um
      laser offers significantly higher vaporesection rates than 70 W power. And
      vaporization mode is a predominant procedure of prostatic vaporesection.

PMID- 24300201
TI  - [Relationship between obstructive sleep apnea-hypopnea syndrome and high
      sensitivity C-reactive protein in non-obese subjects].
AB  - OBJECTIVE: To evaluate the relationship between high sensitivity C-reactive
      protein (hs-CRP) level and the severity of obstructive sleep apnea-hypopnea
      syndrome (OSAHS) in non-obese patients. METHODS: A total of 65 patients with
      suspected OSAHS were recruited. Those with a history of cardiovascular or
      cerebrovascular events, arterial hypertension, chronic obstructive pulmonary
      disease, diabetes mellitus and smoking were excluded. All subjects were examined
      by polysomnography. Subjects with an apnea-hypopnea index (AHI) >= 5 were
      considered to have OSAHS. They were divided into mild, moderate and severe OSAHS
      groups and those with an AHI < 5 were accepted into the control group. The serum
      level of hs-CRP, a biomarker for cardiovascular disease, was measured with
      peripheral venous blood samples. RESULTS: There were 53 males and 12 females with
      a mean age 44.3 +/- 12.2 years and a body mass index (BMI) <25 kg/m(2). The serum
      levels of hs-CRP were significantly higher in OSAHS patients than those of the
      controls (geometric mean [95% confidence interval] 0.416 [0.288-0.600] vs 0.749
      [0.559-1.003] mg/L, P < 0.05). Mean levels of hs-CRP did not differ between the
      group with mild-to-moderate OSAHS and the control group. However, the severe
      OSAHS group had a higher level of hs-CRP than the control group (P = 0.004). A
      significant positive relationship existed between hs-CRP and AHI (r = 0.407, P =
      0.001) . According to stepwise multivariate analysis, only AHI was a reliable
      predictor for elevated serum level of hs-CRP among all these related factors
      (R(2) = 0.166, P = 0.001). CONCLUSION: The severity of OSAHS is associated with
      an elevated serum level of hs-CRP in non-obese patients.

PMID- 24300202
TI  - [Relationship of age-related levels of serum sex hormones with bone mineral
      density decreasing rate in women].
AB  - OBJECTIVE: To explore the relationship between the changes of estrogen, follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) levels and bone mineral
      density (BMD) decreasing rate (BDR) at different skeletal regions and examine the
      effects of hormones levels on BDR. METHODS: An age cross-sectional study was
      conducted in 694 healthy adult women excluded from diseases and drugs affecting
      bone metabolism. Their age range was 20-80 years. The serum concentrations of
      FSH, LH and estradiol (E2) were measured with radioimmunoassay. And BDR was
      measured with a DXA fan-beam bone densitometer at various skeletal regions
      including lumbar spine, left hip and left forearm. RESULTS: The serum levels of
      FSH (r = -0.597 to -0.479, all P < 0.01) and LH r = -0.452 to -0.283, all P <
      0.01) were significantly negatively correlated with BDR at various skeletal
      regions. Meanwhile, the serum level of E2 only had slightly positive correlation
      with hip and distal forearm (r = 0.077 to 0.122, all P < 0.05). After adjusting
      age and body mass index (BMI), serum FSH still had markedly negative correlation
      with BDR at various skeletal regions. However, the correlation coefficients
      became weak. Multiple line regression stepwise analysis revealed that serum FSH
      was a negative determinant factor of BDR at various skeletal regions: 20%-32%
      changes in BDR of various skeletal regions were determined by FSH, while LH only
      produced very small negative effects (0.6%-0.8%) on BDR of lumbar spine. Serum E2
      seemed to be a positive determinant factor of skeletal regions and 2.5%-5.4%
      changes in BDR were determined by E2. The effects of serum FSH on BDR were
      approximately 3.8-12.8 folds than those of serum E2. CONCLUSIONS: BDR is
      correlated with increased FSH in women. The most critical factor for aging
      related BDR is FSH in women while a decreased level of estrogen may be secondary.

PMID- 24300203
TI  - [Comparison of two types of enteral nutrition in patients with intestinal
      fistula].
AB  - OBJECTIVE: To evaluate the impact between home versus hospital enteral nutrition
      in patients with intestinal fistula. METHODS: A clinical trial containing 82
      patients of intestinal fistula with enteral nutrition was conducted. All cases
      were divided into 3 groups: home enteral nutrition (n = 42), hospital enteral
      nutrition (n = 40) and normal control for assessment of quality of life (n = 40).
      The incidence of complications, hospitalization duration, days of enteral
      nutrition and medical costs were compared between two enteral nutrition ways.
      Quality of life was assessed with SF-36 questionnaire at the same time. RESULTS:
      Compared with the hospital enteral nutrition group, the home enteral nutrition
      group had a shorter hospital stay. The costs of treatment showed a significant
      decrease and the quality of life significantly improved. No significant
      difference existed between two types in the length of enteral nutrition and the
      incidence of complications. CONCLUSION: Home enteral nutrition is safe, rational
      and effective for patients with intestinal fistula.

PMID- 24300204
TI  - [Estradiol regulates the expression of small conductance Ca(2)+ activated K(+)
      channel 3 in rat colonic smooth muscle cells in an estrogen receptor alpha
      dependent manner].
AB  - OBJECTIVE: To explore the effects and possible mechanism of 17beta-estradiol on
      the expression of small conductance Ca(2+) activated K(+) channel 3 (SK3) in rat
      colonic smooth muscle cells (SMC). METHODS: The SMC isolated from male SD rats by
      enzymolysis were cultured. And double immunofluorescence staining was used to
      detect the co-expression of SK3 and alpha-actin. Colonic SMC were cultured with
      different concentrations of 17beta-estradiol for 24 h or with 50 nmol/L 17beta
      estradiol at different time points respectively. The expressions of SK3 in
      colonic SMC were measured by real-time quantitative reverse transcription (qRT)
      PCR and Western blotting. The effects of estrogen receptor (ER) inhibitor ICI
      182780, albumin bovine serum-17beta-estradiol (BSA-E2), ERalpha selective agonist
      propyl pyrazole triol (PPT) and ERbeta selective agonist diarylpropionitrile
      (DPN) on SK3 expression were observed. RESULTS: Double immunofluorescence
      staining showed that SK3 and alpha-actin co-expressed in cultured colonic SMC.
      The expression of SK3 of 17beta-estradiol at different concentration (10, 50
      nmol/L) significantly higher than the control group (protein: 0.217 +/- 0.030 and
      0.321 +/- 0.077 vs 0.103 +/- 0.063, mRNA: 1.872 +/- 0.606 and 2.967 +/- 0.659 vs
      0.813 +/- 0.202, all P < 0.05). And 50 nmol/L was the most effective in vitro
      concentration. The peak expression of SK3 appeared at 12 and 24 hour (2.91 and
      3.30-fold in protein vs 3.46 and 3.37-fold in mRNA respectively, all P < 0.05).
      The protein levels of SK3 in ICI 182780 plus 17beta-estradiol group was less than
      17beta-estradiol group (0.111 +/- 0.050 vs 0.351 +/- 0.084, P < 0.05). But it was
      not influenced by BSA-E2. The expressions of SK3 in PPT and E2 groups were both
      higher than control group (0.270 +/- 0.071, 0.309 +/- 0.052 vs 0.087 +/- 0.018,
      both P < 0.05) . However DPN had no effect on SK3 protein levels. CONCLUSIONS:
      SK3 is localized in rat colonic SMC. And 17beta-estradiol increases its
      expression in an ERalpha-dependent manner.

PMID- 24300205
TI  - [Effects of CGRP and CGRP receptor modified mesenchymal stem cells on
      proliferation and phenotypic transformation of vascular smooth muscle cells].
AB  - OBJECTIVE: To explore the effects and mechanism of secretory calcitonin gene
      related peptide (CGRP) and CGRP receptor modified mesenchymal stem cells on
      proliferation and phenotypic transformation of vascular smooth muscle cell.
      METHODS: Firstly (Lenti-GFP-CGRP, referred to CGRP (+/+)) MSCs were transfected
      with high expression lentivirus vector of CGRP (MSCs(CGRP+/+)). Protein secretion
      in the above-mentioned MSCs(CGRP+/+) supernatant was detected with enzyme-linked
      immunosorbent assay (ELISA). And then MSCs(CGRP+/+) was co-cultured with
      VSMCs(RAMP1)(+/+) and VSMCs(RAMP1-/-) respectively. Experimental groups were as
      follows: MSCs +VSMCs MSCs(CGRP+/+) +VSMCs, MSCs(CGRP+/+) +VSMCs(RAMP1)(+/+) and
      MSCs(CGRP+/+) + VSMCs (RAMP1-/-). Flow cytometry was applied to detect the cycle
      variation of smooth muscle cells, thiazolyl blue tetrazolium bromide method for
      detecting the proliferation of smooth muscle cells and Western blot for examining
      the expression changes of spectrin alpha-SM-actin and synthetic protein OPN in
      each group respectively. RESULTS: After the transfection of CGRP(+/+),
      MSCs(CGRP+/+) secreted and expressed CGRP protein, the secretory volume of CGRP
      protein in MSCs(CGRP+/+) increased significantly compared with the control group
      (19.530 +/- 0.498 vs 3.133 +/- 0.160 and 3.120 +/- 0.001, P < 0.05) . After a 72
      h co-culturing with VSMCs, the proliferation of VSMCs in MSCs(CGRP+/+)
      +VSMCs(RAMP1)(+/+)group declined significantly (0.270 +/- 0.263 vs 0.413 +/-
      0.070, P < 0.05) and the number of cells staying in G0 phase significantly
      increased (93.51% +/- 0.38% vs 84.48% +/- 0.31%, P < 0.05) , the expression of
      contractile phenotype protein alpha-SM-actin increased and intermediate phenotype
      OPN declined significantly as compared with MSCsCGRP(+/+) +VSMCs group { (alpha
      SM-actin 102 946 +/- 3847 vs 51 759 +/- 635, P < 0.05), OPN (26 026 +/- 2595 vs
      44 201 +/- 2811, P < 0.05) }; but compared with
      MSCs(CGRP+/+)+VSMCs(RAMP1)(+/+)group, the proliferation of VSMCs in MSCs(CGRP+/+)
      +VSMCs(RAMP1)-/-group significantly increased (0.601 +/- 0.04 vs 0.270 +/- 0.263,
      P < 0.05) while the number of cells staying in G0 phase significantly declined
      (78.57% +/- 0.68% vs 93.51% +/- 0.38%, P < 0.05) . The expression of contractile
      phenotype protein alpha-SM-actin declined while intermediate phenotype OPN
      increased significantly in MSCs(CGRP+/+)+VSMCs(RAMP1)-/-group {alpha-SM-actin (34
      400 +/- 2179 vs 102 946 +/- 3847, P < 0.05), OPN (53 933 +/- 1192 vs 26 026 +/-
      2595, P < 0.05)}. CONCLUSIONS: CGRP gene-modified MSCs may secrete target protein
      stably. And CGRP-modified MSCs inhibits VSMCs phenotypic transformation and cell
      proliferation. It is probably associated with enhanced CGRP effect due to an up
      regulation of CGRP receptor.

PMID- 24300206
TI  - [Effects of fluid resuscitation programs on the levels of inflammatory mediators
      during burn shock stage].
AB  - OBJECTIVE: To explore the effects of different methods of fluid resuscitation on
      the levels of inflammatory mediators during burn shock stage. METHODS: Twenty
      four miniature swine were numbered from 1 to 24 and randomly divided by EXCEL
      2007 into 4 groups of succinylated gelatin, hydroxyethyl starch, Parkland and
      allogeneic plasma (n = 6 each). Severe burn shock model was established.
      Succinylated gelatin, hydroxyethyl starch (130/0.4), Ringer's lactate and swine
      allogenic plasma were used as resuscitation fluid (alternative colloid) according
      to the burn shock recovery principles (beginning at 2 h post-injury). The
      parameters of heart rate (HR), blood pressure (BP), urine volume and central
      venous pressure (CVP) before and within 48 h post-burn were recorded. And the
      levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1beta and IL
      8 were measured at the time of pre-injury as well as 4 h, 8 h, 24 h and 48 h post
      injury. Statistical analyses were performed. RESULTS: All swine survived the
      shock stage. TNF-alpha in succinylated gelatin group was significantly higher at
      48 h post-injury than that in allogeneic plasma group ((351 +/- 74) vs (215 +/-
      44) ng/L, P < 0.05). TNF-alpha in hydroxyethyl starch group was significantly
      higher at 8 h post-injury than that in allogeneic plasma group ((327 +/- 38) vs
      (249 +/- 29) ng/L, P < 0.05). And they were both higher than the pre-burn levels
      (both P < 0.05). Compared with pre-injury ((508 +/- 64) ng/L), the level of IL
      1beta in succinylated gelatin group increased substantially at 4 h ((563 +/- 76)
      ng/L), 8 h ((589 +/- 76) ng/L) and 48 h ((736 +/- 42) ng/L) post-injury (all P <
      0.05). The hydroxyethyl starch group was higher at 48 h post-injury than that at
      pre-injury ((574 +/- 72) vs (492 +/- 41) ng/L, P < 0.05). Also in Parkland group,
      the levels were higher at 24 h and 48 h hours post-injury than that at pre-injury
      ((575 +/- 31), (584 +/- 65) vs (498 +/- 33) ng/L, both P < 0.05). Only
      succinylated gelatin group was significantly higher (P < 0.01) at 48 h post
      injury than allogeneic plasma group ((561 +/- 48) ng/L). Compared with pre-injury
      ((561 +/- 48) ng/L), the level of IL-8 in succinylated gelatin group increased
      significantly at 8 h ((1012 +/- 100) ng/L), 24 h post-burn ((993 +/- 87) ng/L),
      significantly higher than allogeneic plasma group ((866 +/- 99) ng/L) at 24 h
      (all P < 0.05). Although hydroxyethyl starch and Parkland groups increased
      significantly at 4 h post-injury and 8 h, 48 h post-injury versus those at pre
      injury (all P < 0.05). There was no significant difference at each time point
      compared with pre-burn (P > 0.05). CONCLUSIONS: The recovery regimens of
      hydroxyethyl starch and Parkland groups may restrain the levels of inflammatory
      mediators. And the effects are similar to those of allogeneic plasma group.

PMID- 24300207
TI  - [An analysis on HA, NA gene/protein evolution and the variability of antigenicity
      sites of influenza A (H7N9) virus].
AB  - OBJECTIVE: To explore the hemagglutinin (HA), neuraminidase (NA) gene/protein
      evolution and the variability of antigenicity sites of influenza A (H7N9) virus.
      METHODS: The sequences of HA, NA gene and amino acid (AA) were downloaded from
      National Center for Biotechnology Information (NCBI) and the Global Initiative on
      Sharing All Influenza Data (GISAID) database. The bioinformatic software programs
      of Clustal-W, MEGA 5.0, NetNGlyc 1.0 Server and DNAMAN were employed to analyze
      the variations and predict the possible antigenicity sites. RESULTS: A total of
      26 HA gene and AA and 24 NA gene and AA sequences were analyzed. HA, NA gene and
      AA sequence of H7N9 virus were conservative in America but not in Eurasian area.
      The HA and NA gene evolutions could be divided into 2 general systems: Eurasian
      and America. Only one basic AA R (Arg) was close to HA cleavage sites of H7N9
      virus. Regional differences existed between HA protein cleavage and NA protein
      glycosylation sites. And the HA glycosylation sites were conservative. Several
      antigenicity sites of HA and NA protein changed in Eurasian area and America. In
      7 cases, novel H7N9 evolved virus isolated from China were one branch of Eurasian
      area. Five AAs were deleted in stalk region of NA residues 69 to 73. HA protein
      cleavage and glycosylation sites did not carry the variant. However, several
      antigenicity sites of HA and NA protein changed compared with other virus
      strains. CONCLUSIONS: Regional differences exist in HA and NA gene evolution of
      H7N9 virus. The deletion of 5 AAs in stalk and the variation of several
      antigenicity sites of HA and NA protein may lead to an outbreak of H7N9 virus in
      humans.

PMID- 24300208
TI  - [Expressions of immunogenic molecules in low-dose radiotherapy-treated human
      renal clear cell carcinoma 786-0 cells].
AB  - OBJECTIVE: To explore the effects of low-dose radiation on the expression of
      immunogenic membrane molecules calreticulin (CRT) and MHC-I/II on the surface of
      human renal clear cell carcinoma 786-0 cells. METHODS: The inhibitory activity of
      low-dose radiation on cell line 786-0 was examined by CCK-8 assay. And the post
      radiation membrane expressions of CRT, MHC-I and MHC-II were measured by flow
      cytometry while CRT was visualized by immunofluorescence photography. RESULTS:
      The inhibition rates on the proliferative capacities of four 786-0 cell lines
      rose with the incremental radiation doses of 0, 6, 12 and 24 Gy. And the CRT
      expression levels of each experimental group was significantly higher than that
      of the control group (P < 0.001). Along with incremental doses of irradiation,
      the average calreticulin fluorescence intensities increased gradually initially
      and then there was a downward trend. The membrane expressions of MHC-I and MHC-II
      of each experimental group was significantly higher than those of the control
      group (P < 0.05). As the irradiation dose increased, the average MHC-I
      fluorescence intensities increased gradually in a dose-dependent manner.
      CONCLUSION: The low-dose radiotherapy may up-regulate CRT and MHC class I/II
      related with the immunogenicity of tumor cells to induce immune response against
      tumors.

PMID- 24300209
TI  - [Preliminary exploration on submucosal tunneling endoscopic resection for middle
      and lower esophagus submucosal tumors].
AB  - OBJECTIVE: To evaluate the efficacy and safety of submucosal tunneling endoscopic
      resection (STER) in the treatment of middle and lower esophagus submucosal tumors
      (SMT) originating from muscularis propria (MP) layer. METHODS: A total number of
      33 esophagus submucosal tumor (SMT) originating from MP layer underwent tumor
      resection by STER after endoscopic ultrasonography (EUS) and CT examination at
      Endoscopy Center, Department of Gastroenterology, First Affiliated Hospital,
      Nanjing Medical University from March 2012 to March 2013. There were 17 males and
      16 females with an age range of (50 +/- 10) years. Their lesion size, lesion
      origin, pathology, operative duration and complication rate were analyzed.
      RESULTS: Among them, the origins were of submucosal (n = 4, 12.1%), superficial
      muscularis propria layer (SMP) (n = 18, 54.6%), deep muscularis layer (DMP) (n =
      10, 30.3%) and serosa (n = 1, 3.0%). There were single tumor (n = 30, 90.9%),
      double tumors (n = 2, 6.1%) and triple tumors (n = 1, 3.0%). Except for 1 case of
      non-resected hemangioma, 36 operative specimens were examined pathologically,
      including 30 leiomyomas tumors (83.3%), 5 stromal tumors (GIST) (13.9%) and 1
      lipoma tumor (2.8%). Thirty-two lesions were successfully resected by STER with a
      complete resection rate of 97.0%. Average lesion size was (1.7 +/- 1.0) cm and
      average operative duration (49 +/- 26) min. A number of (7.8 +/- 2.5) hemostatic
      clips were used to close the mucosal incision site. Subcutaneous emphysema
      occurred in 3 patients (9.1%) while puncture and pneumothorax developed in one
      case (3.0%). All of them recovered uneventfully through conservative treatments.
      CONCLUSIONS: As a new safe, efficacious and feasible treatment for middle and
      lower esophagus submucosal tumors, STER may completely resect SMT and provide
      accurate histopathological evaluations. And it is feasible to regain the mucosal
      integrity of GI tract and prevent the occurrences of leakage and secondary
      infections.

PMID- 24300210
TI  - [Clinical evaluation of leukocyte differential count in peripheral blood by five
      color flow cytometry].
AB  - OBJECTIVE: To explore the clinical application values of five-color flow
      cytometry for leukocyte differential count in peripheral blood. METHODS:
      Leukocyte differentiation in 265 peripheral blood samples collected at Peking
      University First Hospital from September 2010 to December 2010 was detected by
      standard microscopic cytology as a reference method. Meanwhile, Beckman-Coulter
      LH750 hematology analyzer and FC500 flow cytometer were performed. Then the
      correlations were analyzed between microscopic cytology, hematology analyzer and
      flow cytometry. Forty blood samples collected at Peking University First
      Hospital, Beijing Daopei Hospital and General Hospital of Beijing Military
      Command from August 2010 to November 2010 were analyzed by standard microscopic
      cytology, Beckman-Coulter LH750 hematology analyzer and NAVIOS flow cytometer.
      Then the correlations between microscopy, hematology analyzer and flow cytometry
      were explored to analyze the clinical diagnostic efficiency of flow cytometry.
      RESULTS: Correlation of leukocyte differential count between FC500 flow cytometer
      and standard microscopic cytology was significant (all P < 0.01) . And it was
      superior in the detection of lymphocytes, neutrophils and eosinophils (r = 0.955,
      0.928, 0.876). Moreover, the correlation of leukocyte differential count between
      NAVIOS flow cytometer via manual gate and standard microscopic cytology was
      significant (r > 0.700, all P < 0.01) except for basophils. And it was superior
      in the detection of neutrophils, lymphocytes and blasts (r = 0.950, 0.915,
      0.852). When 1% was set as the cut-off value of immature granulocytes on standard
      microscopic cytology, the sensitivity and specificity of flow cytometry was 87%
      and 76% respectively. When 0.5% was set as the cut-off value of blasts on
      standard microscopic cytology, the sensitivity and specificity of flow cytometry
      stood at 100% and 92% respectively. CONCLUSION: Five-color flow cytometry is well
      correlated with standard microscopic cytology for leukocyte differential count in
      peripheral blood with different flow cytometers, and the sensitivity of detecting
      blasts and immature granulocytes is very excellent.

PMID- 24300211
TI  - Spatially distinct functions of Clb2 in the DNA damage response.
AB  - In budding yeast four mitotic cyclins (Clb1-4) cooperate in a partially redundant
      manner to bring about M-phase specific events, including the apical isotropic
      switch that ends polarized bud growth initiated at bud emergence. How exactly
      this morphogenetic transition is regulated by mitotic CDKs remains poorly
      understood. We have taken advantage of the isotropic bud growth that prevails in
      cells responding to DNA damage to unravel the contribution of mitotic cyclins in
      this cellular context. We find that clb2?, in contrast to the other mitotic
      cyclin mutants, inappropriately respond to the presence of DNA damage. This
      aberrant response is characterized by a Cdc42- and Bni1-dependent but Cln
      independent resumption of polarized bud growth after a brief period of actin
      depolarization. Biochemical and genetic evidence is presented that formally
      excludes the possibility of indirect effects due for instance to unrestrained APC
      activity, untimely mitotic exit or Swe1-mediated CDK inhibition. Importantly, our
      data demonstrate that in order to maintain the characteristic dumbbell arrest
      phenotype upon checkpoint activation Clb2 needs to be efficiently exported into
      the cytoplasm. We propose that the inhibition of mitotic cyclin destruction by
      the DNA damage checkpoint pathway leads to a buildup of Clb2 in the cytoplasm
      where this cyclin can stabilize the apical isotropic switch throughout a G 2/M
      checkpoint arrest. Our study also unveils an essential role of nuclear Clb2 in
      both survival and adaptation to the DNA damage checkpoint, illustrating a
      spatially distinct dual function of this mitotic cyclin in the response to DNA
      damage. 

PMID- 24300212
TI  - Puzzling with online games (BAM-COG): reliability, validity, and feasibility of
      an online self-monitor for cognitive performance in aging adults.
AB  - BACKGROUND: Online interventions are aiming increasingly at cognitive outcome
      measures but so far no easy and fast self-monitors for cognition have been
      validated or proven reliable and feasible. OBJECTIVE: This study examines a new
      instrument called the Brain Aging Monitor-Cognitive Assessment Battery (BAM-COG)
      for its alternate forms reliability, face and content validity, and convergent
      and divergent validity. Also, reference values are provided. METHODS: The BAM-COG
      consists of four easily accessible, short, yet challenging puzzle games that have
      been developed to measure working memory ("Conveyer Belt"), visuospatial short
      term memory ("Sunshine"), episodic recognition memory ("Viewpoint"), and planning
      ("Papyrinth"). A total of 641 participants were recruited for this study. Of
      these, 397 adults, 40 years and older (mean 54.9, SD 9.6), were eligible for
      analysis. Study participants played all games three times with 14 days in between
      sets. Face and content validity were based on expert opinion. Alternate forms
      reliability (AFR) was measured by comparing scores on different versions of the
      BAM-COG and expressed with an intraclass correlation (ICC: two-way mixed;
      consistency at 95%). Convergent validity (CV) was provided by comparing BAM-COG
      scores to gold-standard paper-and-pencil and computer-assisted cognitive
      assessment. Divergent validity (DV) was measured by comparing BAM-COG scores to
      the National Adult Reading Test IQ (NART-IQ) estimate. Both CV and DV are
      expressed as Spearman rho correlation coefficients. RESULTS: Three out of four
      games showed adequate results on AFR, CV, and DV measures. The games Conveyer
      Belt, Sunshine, and Papyrinth have AFR ICCs of .420, .426, and .645 respectively.
      Also, these games had good to very good CV correlations: rho=.577 (P=.001),
      rho=.669 (P<.001), and rho=.400 (P=.04), respectively. Last, as expected, DV
      correlations were low: rho=-.029 (P=.44), rho=-.029 (P=.45), and rho=-.134
      (P=.28) respectively. The game Viewpoint provided less desirable results with an
      AFR ICC of .167, CV rho=.202 (P=.15), and DV rho=-.162 (P=.21). CONCLUSIONS: This
      study provides evidence for the use of the BAM-COG test battery as a feasible,
      reliable, and valid tool to monitor cognitive performance in healthy adults in an
      online setting. Three out of four games have good psychometric characteristics to
      measure working memory, visuospatial short-term memory, and planning capacity.

PMID- 24300213
TI  - Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to
      treat Alzheimer's disease.
AB  - Disabilities caused by neurodegeneration have become one of the main causes of
      mortality in elderly population, with drug distribution to the brain remaining
      one of the most difficult challenges in the treatment of the central nervous
      system (CNS) diseases due to the existence of blood-brain barrier. Lectins
      modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles
      could enhance the drug delivery to the brain following intranasal administration.
      In this study, basic fibroblast growth factor (bFGF) was entrapped in
      nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively
      binds to N-acetylglucosamine on the nasal epithelial membrane for its brain
      delivery. The resulting nanoparticles had uniform particle size and negative zeta
      potential. The brain distribution of the formulations following intranasal
      administration was assessed using radioisotopic tracing method. The areas under
      the concentration-time curve of (125)I-bFGF in the olfactory bulb, cerebrum, and
      cerebellum of rats following nasal application of STL modified nanoparticles (STL
      bFGF-NP) were 1.79-5.17 folds of that of rats with intravenous administration,
      and 0.61-2.21 and 0.19-1.07 folds higher compared with intranasal solution and
      unmodified nanoparticles, respectively. Neuroprotective effect was evaluated
      using Mirror water maze task in rats with intracerebroventricular injection of
      beta-amyloid25-35 and ibotenic acid. The spatial learning and memory of
      Alzheimer's disease (AD) rats in STL-bFGF-NP group were significantly improved
      compared with AD model group, and were also better than other preparations. The
      results were consistent with the value of choline acetyltransferase activity of
      rat hippocampus as well as the histological observations of rat hippocampal
      region. The histopathology assays also confirmed the in vivo safety of STL-bFGF
      NP. These results clearly indicated that STL-NP was a promising drug delivery
      system for peptide and protein drugs such as bFGF to enter the CNS and play the
      therapeutic role. 

PMID- 24300214
TI  - Poly dimethyl diallyl ammonium coated CMK-5 for sustained oral drug release.
AB  - A new oral sustained drug delivery system (DDS) involving a combination of
      inorganic mesoporous material (CMK-5) and organic polymer poly dimethyl diallyl
      ammonium (PDDA) was established to determine its general suitability for use with
      poorly water soluble drugs. Nimodipine, carvedilol and fenofibrate, three
      different drugs with acidic or alkaline properties, were selected as model drugs
      and loaded into carriers. The physicochemical properties of the drug carriers
      were systematically studied using scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and nitrogen adsorption. The structural
      body changes of the composites in release medium, with or without additional
      salts, were also studied using particle sizing systems, nitrogen adsorption and
      zeta potential measurement in order to investigate the sustained release
      mechanism of the drugs. The results obtained showed that sustained release of
      drug from the designed DDS was mainly due to the blockage effect arising from the
      strong swelling of the coated polymers when in contact with release medium.
      Additional salts, when they reached a certain level, allowed a dramatic burst
      release. We believe that our designed sustained DDS provide a new option for
      water insoluble drugs and can be considered as fundamental for those more
      sophisticated DDS increasingly required in modern medical treatments. 

PMID- 24300215
TI  - Quantitative analysis of visible surface defect risk in tablets during film
      coating using terahertz pulsed imaging.
AB  - Tablets are the most common form of solid oral dosage produced by pharmaceutical
      industries. There are several challenges to successful and consistent tablet
      manufacturing. One well-known quality issue is visible surface defects, which
      generally occur due to insufficient physical strength, causing breakage or
      abrasion during processing, packaging, or shipping. Techniques that allow
      quantitative evaluation of surface strength and the risk of surface defect would
      greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed
      to evaluate the surface properties of core tablets with visible surface defects
      of varying severity after film coating. Other analytical methods, such as tensile
      strength measurements, friability testing, and scanning electron microscopy
      (SEM), were used to validate TPI results. Tensile strength and friability
      provided no information on visible surface defect risk, whereas the TPI-derived
      unique parameter terahertz electric field peak strength (TEFPS) provided spatial
      distribution of surface density/roughness information on core tablets, which
      helped in estimating tablet abrasion risk prior to film coating and predicting
      the location of the defects. TPI also revealed the relationship between surface
      strength and blending condition and is a nondestructive, quantitative approach to
      aid formulation development and quality control that can reduce visible surface
      defect risk in tablets. 

PMID- 24300217
TI  - Pain-QuILT: assessing clinical feasibility of a Web-based tool for the visual
      self-report of pain in an interdisciplinary pediatric chronic pain clinic.
AB  - OBJECTIVES: To evaluate clinical feasibility of the Pain-QuILT (previously known
      as the Iconic Pain Assessment Tool) from the perspective of adolescents with
      chronic pain and members of their interdisciplinary health team. The Pain-QuILT
      (PQ), a web-based tool that records the visual self-report of sensory pain in the
      form of time-stamped records, was directly compared with standard interview
      questions that were transformed to a paper-based tool. METHODS: Qualitative, semi
      structured interviews were used to refine the PQ. Adolescents with chronic pain
      aged 12 to 18 years used the PQ and comparator tool (randomized order) to self
      report pain before a scheduled clinic appointment, and then took part in a semi
      structured interview. The health team used these pain reports (PQ and comparator)
      during patient appointments, and later participated in focus group interviews.
      Interview audio recordings were transcribed verbatim and underwent a simple line
      by-line content analysis to identify key concepts. RESULTS: A total of 17
      adolescents and 9 health team members completed the study. All adolescents felt
      that the PQ was easy to use and understand. The median time required for
      completion of the PQ and comparator tool was 3.3 and 3.6 minutes, respectively.
      Overall, 15/17 (88%) of adolescents preferred the PQ to self-report their pain
      versus the comparator. The health team indicated that the PQ was a clinically
      useful tool and identified minor barriers to implementation. DISCUSSION:
      Consultations with adolescents and their health team indicate that the PQ is a
      clinically feasible tool for eliciting detailed self-report records of the
      sensory experience of chronic pain.

PMID- 24300216
TI  - Genetic networks involved in poplar root response to low nitrogen.
AB  - Perception of environmental cues and adaptation to changing environmental
      conditions are crucial for survival of sessile organisms like plants. This is
      even more important for woody perennial species like trees that can occupy a site
      for thousands of years. We have previously shown that under low nitrogen (LN),
      poplar trees display a vigorous and long-lasting root growth associated with
      global transcriptomic reprogramming and an activation of hierarchical genetic
      networks. Here we use computational analysis to better understand the network
      among the genes showing distinct chronological patterns of expression during the
      response. Our analyses confirm the previous findings, define new potential
      signaling pathways and the possible downstream targets of these signaling events.

PMID- 24300218
TI  - The cognitive fusion questionnaire: a preliminary study of psychometric
      properties and prediction of functioning in chronic pain.
AB  - BACKGROUND: Acceptance and Commitment Therapy and the psychological flexibility
      model on which it is based are growing interests for those researching and
      treating chronic pain. One part of this model is a therapeutic process called
      cognitive defusion. Cognitive defusion is a process of experiencing a distinction
      between thoughts and the events or people they describe. This process is intended
      to reduce the dominating psychological influence of thoughts without necessarily
      changing the content or frequency of the thoughts. There are recently developed
      measures of this process but little study of it in people with chronic pain.
      METHODS: This study explored the reliability and validity of the Cognitive Fusion
      Questionnaire (CFQ) within a chronic pain population. A total of 326 adults with
      chronic pain completed this measure and a set of other standard clinical measures
      at the start of treatment in a specialty chronic pain service in the United
      Kingdom. RESULTS: An exploratory factor analysis revealed an interpretable 2
      factor structure within the items of the CFQ. Internal consistency reliability
      was good (alpha=0.87). In the analyses of validity the CFQ significantly
      correlated with general psychological acceptance and pain-related acceptance as
      expected. In multiple regression analyses, which included relevant patient
      background variables, pain, and acceptance of pain, cognitive fusion contributed
      significantly to the explained variance in the prediction of 5 of 6 dependent
      variables tested. DISCUSSION: The CFQ may be a useful measure for further
      research and treatment development.

PMID- 24300220
TI  - A phase 2 study of lower-dose, indomethacin submicron particle capsules
      demonstrates early onset of acute pain relief.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drugs are efficacious for the
      treatment of acute and chronic pain; however, they have the potential for serious
      adverse events (AEs). The objective of this study was to evaluate the efficacy
      and safety of investigational, lower-dose, indomethacin submicron particle
      capsules compared with placebo in a study of patients with postsurgical pain.
      MATERIALS AND METHODS: This phase 2, multicenter, randomized, double-blind,
      single-dose, and placebo-controlled study enrolled 203 patients (18 to 50 y old)
      following extraction of >= 2 third molars who experienced moderate-to-severe pain
      intensity <= 6 hours after surgery. Patients received indomethacin submicron
      particle capsules (20 or 40 mg), celecoxib 400 mg, or placebo. The primary
      efficacy endpoint was the sum of total pain relief over 0 to 8 hours (TOTPAR-8)
      determined from the area under the curve for pain relief over 0 to 8 hours
      following administration of the study drug, where pain relief was measured on a 0
      to 4 scale. Safety and tolerability were also assessed. RESULTS: Mean +/- SE
      TOTPAR-8 scores were 10.8 +/- 1.4 (indomethacin submicron particle capsules 20
      mg), 12.6 +/- 1.3 (indomethacin submicron particle capsules 40 mg), 14.8 +/- 1.3
      (celecoxib), and 3.0 +/- 1.3 (placebo; P<0.001 for active treatments vs.
      placebo). Indomethacin submicron particle capsules treatment groups demonstrated
      better mean TOTPAR over 4 hours than placebo (P<0.001). Similar rates and
      profiles of treatment-emergent AEs were reported by patients across treatment
      groups. DISCUSSION: Lower-dose, indomethacin submicron particle capsules provide
      good overall pain relief in patients with postsurgical pain and are generally
      well tolerated. Indomethacin submicron particle capsules are a potentially
      promising option for treatment of acute pain and warrant further study.

PMID- 24300221
TI  - MPI profile classifications and associated clinical findings among litigating
      motor vehicle collision patients.
AB  - OBJECTIVES: The purpose of this study was to examine differences in precollision,
      pericollision, and postcollision clinical variables across litigating motor
      vehicle collision (MVC) patients who were classified as Dysfunctional (DYS),
      Interpersonally Distressed (ID), or Adaptive Copers (ACs) based on
      Multidimensional Pain Inventory (MPI) profile classifications. MATERIALS AND
      METHODS: A sample of 240 MVC patients who sustained serious physical injuries and
      experienced MVC-related chronic pain completed the MPI and provided responses to
      a semistructured psycholegal interview designed to elicit injury-related and pain
      related symptoms and treatments, determine the presence and impact of
      precollision experiences, and render psychiatric diagnoses and ratings of
      psychological disability. RESULTS: A significant multivariate effect of MPI
      profile group on postcollision variables was revealed, with the DYS and ID groups
      reporting more pain sites than the AC group and the DYS group receiving more
      recommendations for treatment than the AC group. Larger proportions of the DYS
      and ID groups were diagnosed as experiencing major depressive disorder than the
      AC group. A rating of total psychological disability was applied most often to
      members of the ID group, with partial psychological disability applied most often
      to members of the DYS group, and no psychological disability applied most often
      to members of the AC group. DISCUSSION: This study extends the MPI literature by
      establishing the usefulness of the measure in determining those reports of MVC
      related pain and emotional distress that are most likely to be associated with
      postcollision psychological disability. The current study supports the usefulness
      of MPI profile classifications in identifying MVC patients who are likely to
      require and benefit from intensive psychological and other rehabilitative
      interventions.

PMID- 24300219
TI  - Adult sickle cell quality-of-life measurement information system (ASCQ-Me):
      conceptual model based on review of the literature and formative research.
AB  - OBJECTIVES: Research-derived evidence about the impact of sickle cell disease
      (SCD) on the lives of affected adults is lacking. We conducted formative research
      to provide the basis for a comprehensive description of how SCD affects the lives
      of adults, with the goal of developing a SCD-specific quality-of-life measurement
      system. METHODS: We conducted a comprehensive literature review of patient
      reported outcomes, followed by a series of focus groups and structured individual
      interviews with adults with SCD (n=122) and their health care providers (n=15).
      RESULTS: We reviewed 473 abstracts and included 86 articles in the final review.
      The literature revealed broad categories of the impact of SCD and its treatment
      on the lives of adults-pain; emotional distress; social-role functioning; overall
      quality-of-life; and quality of care. We classified 1213 incidents from the focus
      groups and interviews into a taxonomy (16 domains) that met the criterion for
      saturation and was demonstrated to be reliable for the classification of
      incidents. The final conceptual model was built upon the taxonomy. DISCUSSION:
      Our conceptual model was similar to previous models with the effects of pain
      predominating, interwoven with emotional distress, quality of care, and
      stigmatization. We found a broad range of emotions reflected, including positive
      effects of SCD. Items for the quality-of-life measure were derived from the
      taxonomy and the conceptual model may be of use in generating hypotheses for
      clinical research and improving understanding for clinicians of the lived
      experience of adults with SCD.

PMID- 24300222
TI  - Teaching parents to manage pain during infant immunizations: laying the
      foundation for better pain management practices.
AB  - OBJECTIVE: To evaluate knowledge uptake from a parent-directed factsheet about
      managing pain during infant vaccinations, and the added influence of a pretest.
      MATERIALS AND METHODS: Solomon 4-group randomized controlled trial. New mothers
      hospitalized after the birth of an infant were randomized to 1 of 4 groups: 2
      included the intervention (factsheet about pain management) and 2 included the
      control (information on another topic). A pretest was given to 1 intervention and
      1 control group. Following maternal review of allocated information, posttests
      were administered in all groups. Both control groups received the information
      after posttesting. A follow-up telephone survey after 2 months measured knowledge
      retention and utilization of pain management interventions. RESULTS: A total of
      120 mothers participated (July, 2012 to February, 2013); demographics did not
      differ among groups. The 2 factsheet groups demonstrated more knowledge (P<0.05)
      about effective pain management (mean without pretest: 5.6 [SD=2.0]; with
      pretest: 6.9 [1.6]) compared with the 2 control groups (without pretest: 3.2
      [2.2]; with pretest: 3.4 [2.5]) immediately after review; and the factsheet and
      pretest group scored higher than the factsheet only group. In groups with a
      prefactsheet baseline knowledge test, knowledge was higher at follow-up compared
      with baseline. Follow-up knowledge and utilization of pain management
      interventions did not differ among groups. CONCLUSIONS: The factsheet led to
      acute gains in knowledge and knowledge gains persisted after 2 months. Acutely,
      knowledge was bolstered by the pretest. These results can be used to guide future
      research and implementation of the factsheet.

PMID- 24300223
TI  - The first postoperative day: prospective evaluation of pain in adult
      otorhinolaryngologic surgery.
AB  - OBJECTIVES: The aim of the study was to assess postoperative pain within the
      first 24 hours after otorhinolaryngologic surgery and to identify factors
      influencing postoperative pain. METHODS: A total of 8447 patients from 65 German
      hospitals were included in a prospective evaluation using a web-based multicenter
      registry. On the first postoperative day, patients were asked to rate their pain
      using the questionnaires of the German-wide project Quality Improvement in
      Postoperative Pain Treatment including numeric rating scales (0 to 10) for the
      determination of patients' pain on ambulation, maximal pain, and minimal pain.
      Quality Improvement in Postoperative Pain Treatment allowed a standardized
      assessment of patients' characteristics, pain parameters, outcome, and process
      parameters. The influence of these parameters on the patients' postoperative pain
      was estimated by univariate and multivariate statistical analysis. RESULTS: The
      mean pain on ambulation, the maximal pain, and minimal pain were 3.2+/-2.3, 4.3+/
      2.7, and 1.6+/-1.6, respectively. Oral surgery, especially the subgroup of
      patients receiving a tonsillectomy, was related to the highest pain scores (all
      Ps<0.05): pain on ambulation: 4.3+/-2.1; maximal pain: 5.6+/-2.3; minimal pain:
      2.4+/-1.6. Several factors were independently associated with more maximal pain:
      female sex, younger age, chronic pain, type of surgery, no pain counseling, no
      usage of a sedative and/or a nonopioid as premedication, usage of a nonopioid in
      the recovery room and/or ward, and usage of a cold pack on ward. DISCUSSION:
      Analgesia and perioperative pain management in otorhinolaryngologic surgery seems
      to be highly variable. After otorhinolaryngologic surgery many patients seem to
      receive less analgesia than needed or ineffective analgesic drug regimes.

PMID- 24300224
TI  - Effects of tDCS-induced motor cortex modulation on pain in HTLV-1: a blind
      randomized clinical trial.
AB  - OBJECTIVE: We aimed to evaluate the effects of transcranial direct current
      stimulation (tDCS) on chronic pain in human T-lymphotropic virus type I-infected
      patients. MATERIALS AND METHODS: This is a sham-controlled randomized clinical
      trial. Twenty participants were randomized to receive active or sham anodal tDCS
      over the primary motor cortex (M1), with 2 mA, 25 cm electrodes, for 20 minutes
      on 5 consecutive days. Pain intensity was measured at baseline and after each day
      of treatment using a Visual Analog Scale. Associated factors such as pain
      components description, pressure pain threshold, and Timed Up and Go task were
      also assessed. RESULTS: Mild adverse events were reported by 100% of patients in
      the tDCS group and 90% in the sham group. Comparison of daily Visual Analog Scale
      pain scores from both groups demonstrated a significant effect for the factor
      Time (P<0.001), but not for Group (P=0.13) or Time*Group interaction (P=0.06).
      There were 8 (80%) responders (reduction of 50% or more in pain intensity) in the
      tDCS group and 3 (30%) in the sham group (P=0.03). Both groups demonstrated
      improvements for most associated factors evaluated. However, there was no
      difference in between-groups comparison analyses. CONCLUSIONS: The analysis of
      the main outcomes in this study did not demonstrate a significant advantage of
      anodal tDCS applied to M1 in patients with human T-lymphotropic virus type I and
      chronic pain in comparison with sham tDCS, although secondary analysis suggests
      some superiority of active tDCS over sham. The large placebo effect observed in
      this study may explain the small differences between sham versus active tDCS.

PMID- 24300225
TI  - What are patient beliefs and perceptions about exercise for nonspecific chronic
      low back pain? A systematic review of qualitative studies.
AB  - OBJECTIVES: The global burden of low back pain is the highest ranked condition
      contributing to years of living with disability. Exercise is moderately
      effective, and adherence to exercise may improve if participants are engaged.
      Identification of elements that enhance engagement would enable clinicians to
      prescribe appropriate interventions. The review objective was to identify and
      synthesize qualitative empirical studies that have explored beliefs about
      exercise therapy of people with nonspecific chronic low back pain. METHODS: Two
      independent reviewers conducted a structured review and metasynthesis informed by
      Cochrane and Campbell Collaboration guidelines and the PRISMA statement. Fifteen
      papers were included for data extraction, method quality assessment, and thematic
      analysis. RESULTS: Four key themes emerged: (1) perceptions and classification of
      exercise; (2) role and impact of the health professional; (3) exercise and
      activity enablers/facilitators; (4) exercise and activity barriers. Participants
      believed that there were distinctions between general activity, real/fitness
      exercise, and medical exercise. Levels of acquired skills and capability and
      participant experience with exercise culture require consideration in program
      design. People participating in exercise classes and group work may be more
      comfortable when matched for abilities and experience. When an intervention
      interferes with everyday life and appears to be ineffective or too difficult to
      implement, people make a reasoned decision to discontinue. DISCUSSION: People are
      likely to prefer and participate in exercise or training programs and activities
      that are designed with consideration of their preferences, circumstances, fitness
      levels, and exercise experiences.

PMID- 24300226
TI  - Co-bedding between preterm twins attenuates stress response after heel lance:
      results of a randomized trial.
AB  - OBJECTIVE: To examine the effect of co-bedding between preterm twins on stress
      response after heel lance. METHODS: Using a multisite randomized controlled trial
      design, stable preterm twins (67 sets, N=134 infants) between 28 and 36 completed
      weeks' gestational age, stratified by gestational age (<= and >32 weeks) and
      site, were randomly assigned to a co-bedding group, cared for continuously in the
      same incubator or crib or a standard care group, cared for in a separate
      incubator or crib, and underwent a medically indicated heel lance after at least
      24 hours and no greater than 10 days of group allocation. The reported outcome
      was cortisol from saliva samples from 89 twins (n=49 co-bedding, n=40 standard
      care) collected immediately before the heel lance (baseline levels) and 113 twins
      (n=58 co-bedding, n=55 standard care) collected 20 minutes after heel lance
      (stress levels) as an index of stress response. RESULTS: No group differences
      were noted in baseline salivary cortisol levels: 0.36 MUg/dL (SD 0.25) in the co
      bedding group and 0.43 MUg/dL (SD 0.50) in the standard care group. Twenty
      minutes after lance, levels were significantly lower in the co-bedding group,
      0.28 MUg/dL (SD 0.25) versus 0.50 MUg/dL (SD 0.73) in the standard group
      (P=0.04). Similarly, the mean of paired changes in salivary cortisol from
      baseline was lower in the co-bedding group (-0.06 MUg/dL) compared with the
      standard care group (0.14 MUg/dL, P<0.05). DISCUSSION: Co-bedding attenuates the
      stress response of preterm twins undergoing heel lance. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT009176.

PMID- 24300227
TI  - The interleukin-1alpha gene C>T polymorphism rs1800587 is associated with
      increased pain intensity and decreased pressure pain thresholds in patients with
      lumbar radicular pain.
AB  - OBJECTIVES: Previous studies have suggested that many inflammatory cytokines,
      including interleukin (IL)-1alpha, may be associated with lumbar radicular pain
      after disk herniation. In the present study, we examined how variability of the
      IL-1alpha gene affects pain intensity and the pressure pain threshold (PPT) in
      patients with symptomatic disk herniation. MATERIALS AND METHODS: A total of 121
      patients with lumbar radicular pain due to disk herniation were recruited from
      Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The
      primary outcome measures were pain intensity scores for the lower back and legs
      using a visual analog pain scale (VAS) and PPT for the gluteal muscles.
      Genotyping was carried out using a predesigned TaqMan assay for IL-1alpha
      rs1800587. The effect of the IL-1alpha genotype on the VAS and PPT was analyzed
      by repeated measure analyses of variance. RESULTS: The IL-1alpha gene C>T
      polymorphism rs1800587 affected VAS and PPT scores in patients with symptomatic
      disk herniation. Patients with the CT/TT genotype reported a higher VAS leg pain
      intensity (P=0.002) and also a lower PPT in the gluteal muscles (left P=0.016;
      right P=0.016) compared with patients with the CC genotype during 1 year of
      follow-up. DISCUSSION: The present data show that the IL-1alpha CT/TT genotype
      rs1800587 may be associated with increased pain intensity and corresponding
      reduced PPT during the first year after disk herniation.

PMID- 24300228
TI  - Measuring outcomes in pain clinical trials: the importance of empirical support
      for measure selection.

PMID- 24300229
TI  - Fronto-central monomorphic theta activity as EEG pattern of ictal psychosis.

PMID- 24300230
TI  - A systematic review of closure versus medical therapy for preventing recurrent
      stroke in patients with patent foramen ovale and cryptogenic stroke or transient
      ischemic attack.
AB  - The optimal treatment for secondary prevention in patients who have a patent
      foramen ovale (PFO) and history of cryptogenic stroke is still uncertain and
      controversial. In view of this, we performed a systematic review of randomized
      controlled trials (RCTs) to investigate whether PFO closure was superior to
      medical therapy for prevention of recurrent stroke or transient ischemic attack
      (TIA) in patients with PFO after cryptogenic stroke. We searched the Cochrane
      Central Register of Controlled Trials, Embase, PubMed, Web of Science, and
      ClinicalTrials.gov. Three randomized controlled trials with a total of 2303
      patients were included and analyzed. A fixed-effect model was used by Review
      Manager 5.2 (RevMan 5.2) software. The pooled risk ratio (RR) of recurrent stroke
      or TIA was 0.70, with 95% confidence interval (CI) = 0.47 to 1.04, p = 0.08. The
      results were similar in the incidence of death and adverse events, and the pooled
      RR was 0.92 (95% CI = 0.34 to 2.45, p = 0.86) and 1.08 (95% CI = 0.93 to 1.26, p
      = 0.32), respectively. The data of this systematic review did not show
      superiority of closure over medical therapy for secondary prevention after
      cryptogenic stroke. Due to some limitations of the included studies, more
      randomized controlled trials are needed for further investigation regarding this
      field.

PMID- 24300231
TI  - Breakdown of the blood-ocular barrier as a strategy for the systemic use of
      nanosystems.
AB  - Several drug delivery systems have been proposed to overcome physiological
      barriers, improving ocular bioavailability. Systemic routes are seldom used due
      to the blood-ocular barrier. Novel drug delivery systems based on nanotechnology
      techniques have been developed to overcome ocular physiological barriers. This
      non-systematic review suggests the utilization of a transitory blood-ocular
      breakdown to allow the access of drugs by nanotechnology drug delivery systems
      via the systemic route. We discuss the possible ways to cause the breakdown of
      the blood-ocular barrier: acute inflammation caused by intraocular surgery,
      induced ocular hypotony, and the use of inflammatory mediators. The suitability
      of use of the systemic route and its toxic effects are also discussed in this
      article. 

PMID- 24300232
TI  - Impact of molecular weight on lymphatic drainage of a biopolymer-based imaging
      agent.
AB  - New lymphatic imaging technologies are needed to better assess immune function
      and cancer progression and treatment. Lymphatic uptake depends mainly on particle
      size (10-100 nm) and charge. The size of carriers for imaging and drug delivery
      can be optimized to maximize lymphatic uptake, localize chemotherapy to lymphatic
      metastases, and enable visualization of treatment deposition. Toward this end,
      female BALB/c mice were injected subcutaneously in the hind footpad or forearm
      with a series of six different molecular weight hyaluronan (HA) near-infrared dye
      (HA-IR820) conjugates (ca. 5-200 nm). Mice were imaged using whole body
      fluorescent imaging over two weeks. HA-IR820 fluorescence was clearly visualized
      in the draining lymphatic capillaries, and in the popliteal and iliac or axillary
      lymph nodes. The 74-kDa HA-IR820 had the largest lymph node area-under-the-curve.
      In contrast to prior reports, mice bearing limb tumors exhibited three-fold
      longer retention of 74-kDa HA-IR820 in the popliteal node compared to mice
      without tumors. HA conjugate kinetics and disposition can be specifically
      tailored by altering their molecular weight. The specific lymphatic uptake and
      increased nodal retention of HA conjugates indicate significant potential for
      development as a natural biopolymer for intralymphatic drug delivery and imaging.

PMID- 24300233
TI  - Hydrotalcite Intercalated siRNA: Computational Characterization of the Interlayer
      Environment.
AB  - Using molecular dynamics (MD) simulations, we explore the structural and
      dynamical properties of siRNA within the intercalated environment of a Mg:Al 2:1
      Layered Double Hydroxide (LDH) nanoparticle. An ab initio force field (Condensed
      phase Optimized Molecular Potentials for Atomistic Simulation Studies: COMPASS)
      is used for the MD simulations of the hybrid organic-inorganic systems. The
      structure, arrangement, mobility, close contacts and hydrogen bonds associated
      with the intercalated RNA are examined and contrasted with those of the isolated
      RNA. Computed powder X-ray diffraction patterns are also compared with related
      LDH-DNA experiments. As a method of probing whether the intercalated environment
      approximates the crystalline or rather the aqueous state, we explore the
      stability of the principle parameters (e.g., the major groove width) that
      differentiate both A- and A'- crystalline forms of siRNA and contrast this with
      recent findings for the same siRNA simulated in water. We find the crystalline
      forms remain structurally distinct when intercalated, whereas this is not the
      case in water. Implications for the stability of hybrid LDH-RNA systems are
      discussed. 

PMID- 24300234
TI  - Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby
      Canine Kidney (MDCK) Cells Grown under Differentiation Conditions.
AB  - The expression levels of genes involved in drug and nutrient absorption were
      evaluated in the Madin-Darby Canine Kidney (MDCK) in vitro drug absorption model.
      MDCK cells were grown on plastic surfaces (for 3 days) or on Transwell(r)
      membranes (for 3, 5, 7, and 9 days). The expression profile of genes including
      ABC transporters, SLC transporters, and cytochrome P450 (CYP) enzymes was
      determined using the Affymetrix(r) Canine GeneChip(r). Expression of genes whose
      probe sets passed a stringent confirmation process was examined. Expression of a
      few transporter (MDR1, PEPT1 and PEPT2) genes in MDCK cells was confirmed by RT
      PCR. The overall gene expression profile was strongly influenced by the type of
      support the cells were grown on. After 3 days of growth, expression of 28% of the
      genes was statistically different (1.5-fold cutoff, p < 0.05) between the cells
      grown on plastic and Transwell(r) membranes. When cells were differentiated on
      Transwell(r) membranes, large changes in gene expression profile were observed
      during the early stages, which then stabilized after 5-7 days. Only a small
      number of genes encoding drug absorption related SLC, ABC, and CYP were detected
      in MDCK cells, and most of them exhibited low hybridization signals. Results from
      this study provide valuable reference information on endogenous gene expression
      in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme
      interaction studies, and help interpret the contributions of various transporters
      and metabolic enzymes in studies with MDCK cells. 

PMID- 24300235
TI  - Confocal imaging of single mitochondrial superoxide flashes in intact heart or in
      vivo.
AB  - Mitochondrion is a critical intracellular organelle responsible for energy
      production and intracellular signaling in eukaryotic systems. Mitochondrial
      dysfunction often accompanies and contributes to human disease. Majority of the
      approaches that have been developed to evaluate mitochondrial function and
      dysfunction are based on in vitro or ex vivo measurements. Results from these
      experiments have limited ability in determining mitochondrial function in vivo.
      Here, we describe a novel approach that utilizes confocal scanning microscopy for
      the imaging of intact tissues in live aminals, which allows the evaluation of
      single mitochondrial function in a real-time manner in vivo. First, we generate
      transgenic mice expressing the mitochondrial targeted superoxide indicator,
      circularly permuted yellow fluorescent protein (mt-cpYFP). Anesthetized mt-cpYFP
      mouse is fixed on a custom-made stage adaptor and time-lapse images are taken
      from the exposed skeletal muscles of the hindlimb. The mouse is subsequently
      sacrificed and the heart is set up for Langendorff perfusion with physiological
      solutions at 37  degrees C. The perfused heart is positioned in a special chamber
      on the confocal microscope stage and gentle pressure is applied to immobilize the
      heart and suppress heart beat induced motion artifact. Superoxide flashes are
      detected by real-time 2D confocal imaging at a frequency of one frame per second.
      The perfusion solution can be modified to contain different respiration
      substrates or other fluorescent indicators. The perfusion can also be adjusted to
      produce disease models such as ischemia and reperfusion. This technique is a
      unique approach for determining the function of single mitochondrion in intact
      tissues and in vivo. 

PMID- 24300236
TI  - Tissue transglutaminase in Alzheimer's disease - facts and fiction: a reply to
      "Tissue transglutaminase is a biochemical marker for Alzheimer's disease".

PMID- 24300237
TI  - Overexpression of 12/15-lipoxygenase increases anxiety behavior in female mice.
AB  - The 12/15-lipoxygenase (12/15-LO) is an enzyme widely distributed in the central
      nervous system, and it has been involved in the neurobiology of Alzheimer's
      disease. However, whether this pathway is also involved in neuropsychiatry
      disorders including anxiety remain to be investigated. In this study we
      investigated whether genetic over-expression of 12/15-LO (H12/15-LO) modulates
      some elevated plus maze and Y-maze behaviors. While we observed that H12/15LO
      mice at the age of 12 months did not differ from wild type in the elevated plus
      maze paradigm, when they reached the age of 15 months, they manifested an
      increased anxiety-like behavior compared with controls. By contrast, no
      differences between the 2 groups at both ages when they were tested for working
      memory in the Y-maze paradigm. Additionally, we found that the change in anxiety
      was associated with a reduction in phosphorylation of the transcription factor
      CREB (cAMP response element-binding protein), and a significant increase in the
      synaptic protein synaptophysin. Taken together our findings suggest a novel role
      for 12/15-LO in the pathogenesis of anxiety-like behavior. 

PMID- 24300238
TI  - Targeted high-throughput sequencing identifies a TARDBP mutation as a cause of
      early-onset FTD without motor neuron disease.
AB  - Targeted high-throughput sequencing of many amyotrophic lateral sclerosis (ALS)
      and fronto-temporal dementia (FTD) genes in parallel has the potential to reveal
      novel ALS- and/or FTD-phenotypes and to provide missing links on the ALS-FTD
      continuum. For example, although the 43-kDa transactive response DNA binding
      protein is the major pathologic hallmark linking ALS and FTD, mutations in the
      gene encoding 43-kDa transactive response DNA binding protein (TARDBP) have been
      appreciated only as a cause of ALS-phenotypes, but not yet of pure FTD. Thus, the
      genetic link is not yet well substantiated that TARDBP mutations can cause the
      full spectrum of the ALS-FTD continuum. High-throughput sequencing of 18 ALS and
      FTD genes in an index patient presenting with early-onset pure (behavioral) FTD
      and a positive family history for ALS revealed an established TARDBP mutation,
      A382T. This finding demonstrates that a TARDPB mutation can cause early-onset
      pure FTD without evidence for ALS even in advanced FTD disease stages. Moreover,
      it indicates that TARDPB screening might be considered even in young patients
      with "pure" neuropsychiatric disturbances and without evidence of
      neurodegenerative disease in the parental generation. 

PMID- 24300239
TI  - Dysregulation of glucose metabolism is an early event in sporadic Parkinson's
      disease.
AB  - Unlike most other cell types, neurons preferentially metabolize glucose via the
      pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting
      the PPP in neuronal cell models causes cell death. In rodents, inhibition of this
      pathway causes selective dopaminergic cell death leading to motor deficits
      resembling parkinsonism. Using postmortem human brain tissue, we characterized
      glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's
      disease (AD), and controls. AD brains showed increased nicotinamide adenine
      dinucleotide phosphate (NADPH) production in areas affected by disease. In PD
      however, increased NADPH production was only seen in the affected areas of late
      stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate
      dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent
      assay, showed a reduction in the putamen of early-stage PD and interestingly in
      the cerebellum of early and late-stage PD. Importantly, there was no decrease in
      enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest
      that down-regulation of PPP enzymes and a failure to increase antioxidant reserve
      is an early event in the pathogenesis of sporadic PD. 

PMID- 24300240
TI  - Analysis of embryonic and larval zebrafish skeletal myofibers from dissociated
      preparations.
AB  - The zebrafish has proven to be a valuable model system for exploring skeletal
      muscle function and for studying human muscle diseases. Despite the many
      advantages offered by in vivo analysis of skeletal muscle in the zebrafish,
      visualizing the complex and finely structured protein milieu responsible for
      muscle function, especially in whole embryos, can be problematic. This hindrance
      stems from the small size of zebrafish skeletal muscle (60 MUm) and the even
      smaller size of the sarcomere. Here we describe and demonstrate a simple and
      rapid method for isolating skeletal myofibers from zebrafish embryos and larvae.
      We also include protocols that illustrate post preparation techniques useful for
      analyzing muscle structure and function. Specifically, we detail the subsequent
      immunocytochemical localization of skeletal muscle proteins and the qualitative
      analysis of stimulated calcium release via live cell calcium imaging. Overall,
      this video article provides a straight-forward and efficient method for the
      isolation and characterization of zebrafish skeletal myofibers, a technique which
      provides a conduit for myriad subsequent studies of muscle structure and
      function. 

PMID- 24300241
TI  - A nationwide survey of Aicardi-Goutieres syndrome patients identifies a strong
      association between dominant TREX1 mutations and chilblain lesions: Japanese
      cohort study.
AB  - OBJECTIVES: Aicardi-Goutieres syndrome (AGS) is a rare, genetically determined,
      early onset progressive encephalopathy associated with autoimmune manifestations.
      AGS is usually inherited in an autosomal recessive manner. The disease is rare,
      therefore the clinical manifestations and genotype-phenotype correlations,
      particularly with regard to autoimmune diseases, are still unclear. Here we
      performed a nationwide survey of AGS patients in Japan and analysed the genetic
      and clinical data. METHODS: Patients were recruited via questionnaires sent to
      paediatric or adult neurologists in Japanese hospitals and institutions. Genetic
      analysis was performed and clinical data were collected. RESULTS: Fourteen AGS
      patients were identified from 13 families; 10 harboured genetic mutations. Three
      patients harboured dominant-type TREX1 mutations. These included two de novo
      cases: one caused by a novel heterozygous p.His195Tyr mutation and the other by a
      novel somatic mosaicism resulting in a p.Asp200Asn mutation. Chilblain lesions
      were observed in all patients harbouring dominant-type TREX1 mutations. All three
      patients harbouring SAMHD1 mutations were diagnosed with autoimmune diseases, two
      with SLE and one with SS. The latter is the first reported case. CONCLUSION: This
      study is the first to report a nationwide AGS survey, which identified more
      patients with sporadic AGS carrying de novo dominant-type TREX1 mutations than
      expected. There was a strong association between the dominant-type TREX1
      mutations and chilblain lesions, and between SAMHD1 mutations and autoimmunity.
      These findings suggest that rheumatologists should pay attention to possible
      sporadic AGS cases presenting with neurological disorders and autoimmune
      manifestations.

PMID- 24300242
TI  - Emergency department visits and hospitalizations for digoxin toxicity: United
      States, 2005 to 2010.
AB  - BACKGROUND: Recent data on digoxin prescribing and adverse events are lacking but
      could help inform the management of digoxin in contemporary heart failure
      treatment. METHODS AND RESULTS: We determined nationally representative numbers
      and rates of emergency department (ED) visits for digoxin toxicity in the United
      States using 2005 to 2010 reports from the National Electronic Injury
      Surveillance System-Cooperative Adverse Drug Event Surveillance project and the
      National Ambulatory (and Hospital Ambulatory) Medical Care Surveys. Based on 441
      cases, an estimated 5156 (95% confidence interval [CI], 2663-7648) ED visits for
      digoxin toxicity occurred annually in the United States; more than three fourths
      (78.8% [95% CI, 73.5%-84.1%]) resulted in hospitalization. Serum digoxin level
      was >=2.0 ng/mL for 95.8% (95% CI, 93.2%-98.4%) of estimated ED visits with
      levels reported (n=251 cases). The rate of ED visits per 10 000 outpatient
      prescription visits among patients>=85 years was twice that of patients 40 to 84
      years (rate ratio, 2.4 [95% CI, 1.2-5.0]); among women, the rate was twice that
      of men (rate ratio, 2.3 [95% CI, 1.1-4.7]). Digoxin toxicity accounted for an
      estimated 1.0% (95% CI, 0.6%-1.4%) of ED visits for all adverse drug events among
      patients>=40 years, but an estimated 3.3% (95% CI, 2.3%-4.4%) of ED visits and
      5.9% (95% CI, 4.0%-7.9%) of hospitalizations for all adverse drug events among
      patients>=85 years. Estimated annual ED visits and hospitalizations remained
      relatively constant from 2005 to 2010. CONCLUSIONS: Digoxin toxicity is not
      declining; more careful prescribing to high-risk groups and improved monitoring
      of serum levels might be needed to reduce morbidity from outpatient digoxin use.

PMID- 24300243
TI  - Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis
      after myocardial infarction.
AB  - BACKGROUND: CD4+ cells are implicated in the healing process after myocardial
      infarction (MI). We sought to investigate the role of interleukin-23 (IL-23)
      deficiency, a cytokine important in differentiation of CD4+ cells, in scar
      formation of the ischemic heart. METHODS AND RESULTS: MI was performed in wild
      type and IL23p19-/- mice. Thirty-day mortality, hemodynamic function 4 days after
      MI and myocardial inflammation, and remodeling 4 and 30 days after MI were
      examined. Differentiation of fibroblasts from infarcted and noninfarcted hearts
      into myofibroblasts was examined under basal conditions and after stimulation
      with interferon-gamma, IL-17alpha and IL-23. Interleukin-23p19-/- mice showed
      higher expression of proinflammatory cytokines and immune cell infiltration in
      the scar early after MI compared with wild-type mice. A stronger interferon
      gamma/Th1 reaction seemed to be responsible for the increased inflammation under
      IL-23 deficiency. Expression of alpha-smooth muscle actin (alpha-SMA), collagen I
      and III was significantly higher in the heart tissue and isolated cardiac
      fibroblasts 4 days after MI in the wild-type mice. Interleukin-23p19-/- mice
      showed impaired healing compared with wild-type mice, as seen by significantly
      higher mortality because of ventricular rupture (40% higher after 30 days) and
      stronger left ventricular dilation early after MI. Stimulation of cardiac
      fibroblasts with interferon-gamma, the main Th1 cytokine, but not with IL-23 or
      IL-17alpha, led to a significant downregulation of alpha-smooth muscle actin,
      collagen I and III and decreased migration and differentiation to myofibroblasts.
      CONCLUSIONS: IL-23 deficiency leads to increased myocardial inflammation and
      decreased cardiac fibroblast activation, associated with impaired scar formation
      and adverse remodeling after MI.

PMID- 24300244
TI  - Emergency airway management by paramedics: comparison between standard
      endotracheal intubation, laryngeal mask airway, and I-gel.
AB  - The aim of this study was to investigate whether briefly trained paramedics would
      be able to successfully intubate by endotracheal intubation (ETI) and using the
      laryngeal mask airway (LMA) and the I-gel in a manikin model. After the
      completion of a questionnaire, a brief educational session, and presentation of
      ETI, LMA, and I-gel, 72 paramedics were randomly allocated to intubate an adult
      manikin. The success rate for I-gel was higher than that for LMA (P<0.001) and
      ETI (P<0.001), and the insertion time for I-gel was significantly shorter than
      that for LMA (P<0.001) or during ETI (P<0.001). There was a statistically
      significant association between the experience level of paramedics and insertion
      time only for the LMA (P=0.012). In addition, the mean insertion time values were
      significantly affected by the accuracy of the answers to the theoretical
      questions (P<0.05 for all questions). Paramedics should lay greater emphasis on
      airway management using supraglottic devices, especially I-gel because of its
      shorter time of insertion. 

PMID- 24300245
TI  - Prehospital intranasal evaporative cooling for out-of-hospital cardiac arrest: a
      pilot, feasibility study.
AB  - Intranasal evaporative cooling presents a novel means of initiating therapeutic
      hypothermia after an out-of-hospital cardiac arrest (OHCA). Few studies have
      evaluated the use of intranasal therapeutic hypothermia using the Rhinochill
      device in the prehospital setting. We sought to evaluate the use of Rhinochill in
      the Physician Response Unit of London's Air Ambulance, aiming to describe the
      feasibility of employing it during prehospital resuscitation for OHCA. We
      prospectively evaluated the Rhinochill device over a 7-month period. Inclusion
      criteria for deployment included: age above 18 years, Physician Response Unit on
      scene within maximum of 10 min after return-of-spontaneous circulation (ROSC),
      witnessed OHCA or unwitnessed downtime of less than 10 min, pregnancy not
      suspected, normal nasal anatomy, and likely ICU candidate if ROSC were to be
      achieved. Thirteen patients were included in the evaluation. The average time
      from the 999 call to initiation of cooling was 39.5 min (range 22-61 min). The
      average prehospital temperature change in patients who achieved ROSC was -1.9
      degrees C. Patients were cooled for an average of 38 min prehospital. In all
      cases, the doctor and paramedic involved with the resuscitation reported that the
      Rhinochill was easy to set up and use during resuscitation and that it did not
      interfere with standard resuscitation practice. Intranasal evaporative cooling
      using the Rhinochill system is feasible in an urban, prehospital,
      doctor/paramedic response unit. Cooling with Rhinochill was not found to
      interfere with prehospital resuscitation and resulted in significant core body
      temperature reduction. Further research on the potential benefit of intra-arrest
      and early initiation of intranasal evaporative cooling is warranted. 

PMID- 24300246
TI  - Blood culture diagnostic yield in a paediatric emergency department.
AB  - OBJECTIVES: Blood culture (BC) is one of the most commonly used microbiological
      tests in the paediatric emergency department (PED) despite its lack of immediate
      diagnostic utility. Our objectives were to uncover the reasons for BC in the PED,
      to review adherence to the current protocol for this technique, and to analyse
      the diagnostic yield (DY) of BC in localized bacterial infections. PATIENTS AND
      METHODS: Retrospective study including patients younger than 18 years with a BC
      obtained in the PED of a tertiary care hospital in 2011. Patients with
      bacteraemia risk factors (immunosuppressant condition, long-term vascular
      catheter, prosthetic valve or ventriculoperitoneal shunt, and hospitalization or
      aggressive diagnostic or therapeutic procedure in the previous week) were
      excluded. RESULTS: Two thousand and sixty-two BCs were included. Fever without
      source (FWS) (34.3%) and pneumonia (10.1%) were the main indications for BC.
      Twenty-five per cent of BCs did not adhere to protocol: FWS (115 cases),
      mononucleosic syndrome (83 cases) and acute gastroenteritis (78 cases)
      represented half of these. The global DY by BC was 2.0%. Streptococcus pneumoniae
      was the main isolated microorganism (41.4%) and pneumonia was the main associated
      pathology (22%). All of the BCs with non-adhered-to protocol were negative. All
      of the BCs obtained for noncomplicated bacterial skin and soft tissue infection
      were negative. CONCLUSION: FWS is the main reason for BC in the PED. One-quarter
      of the BCs were not indicated, with the DY null in these cases. Due to the low DY
      in certain localized bacterial infections, a strict individualized ordering of BC
      in these cases should be considered.

PMID- 24300247
TI  - Prevalence of symptomatic rotator cuff ruptures after shoulder trauma: a
      prospective cohort study.
AB  - OBJECTIVE: After shoulder trauma, most fractures and dislocations are easily
      recognized on radiographic examination; however, the opposite is true for rotator
      cuff injuries. As a consequence, shoulder complaints may persist or arise due to
      unrecognized cuff injury. The objective of this study was to investigate the
      prevalence of shoulder pain and symptomatic rotator cuff ruptures 1 year after
      shoulder trauma without fracture or dislocation. PATIENTS AND METHODS: This
      prospective descriptive study included all the patients presented at our
      emergency department between January 2007 and January 2008 after a trauma to the
      shoulder without fracture or dislocation. One year after trauma, this cohort was
      interviewed by telephone and re-examined at the outpatient clinic on indication.
      RESULTS: Of the 217 patients included, all had been pain-free before the trauma.
      One year after trauma, 69 patients (32%) were still suffering from shoulder pain.
      Of these patients, 31 were re-examined and 27 had already been re-examined in the
      meantime. In total, 20 of these 58 patients (34%) were diagnosed with a
      symptomatic rotator cuff rupture, representing a prevalence of 9% among the
      included patients. CONCLUSION: Emergency physicians should be aware that normal
      radiography does not exclude the presence of a rotator cuff tear in patients with
      a history of shoulder trauma. Regular follow-up is essential for discovering
      rotator cuff injuries. In this study, 32% still suffered from shoulder pain 1
      year after shoulder trauma, and re-examination revealed a prevalence of 9%
      symptomatic rotator cuff ruptures.

PMID- 24300248
TI  - Developing a culture of emergency preparedness education in nursing.
AB  - Many new nursing leaders assuming deanships, assistant, or interim deanships have
      limited education, experience, or background to prepare them for the job. 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, challenges, and opportunities that face academic executive
      teams, such as negotiating an executive contract, obtaining faculty lines,
      building effective work teams, managing difficult employees, and creating nimble
      organizational structure to respond to changing consumer, healthcare delivery,
      and community needs. The authors welcome counterpoint discussions with readers. 

PMID- 24300249
TI  - Use of collaborative testing to promote nursing student success.

PMID- 24300250
TI  - A writing intensive introductory course for RN to BSN students.
AB  - This article describes learning strategies used with RN to BSN students in their
      1st nursing course to successfully learn how to write formal papers using the
      American Psychological Association (APA) format. This 1st nursing course, a
      writing intensive, requires 4 short papers with self, peer, and teacher critiques
      and opportunities to rewrite. Students learn the style of professional nursing
      discourse, mastery of APA format, and development of additional skills in
      following directions and in critiquing their own work. An additional benefit is
      to enhance learning about professional nursing topics. By mastering writing
      skills in this initial course, students are able to successfully complete writing
      assignments in future courses and, in some cases, move on to publication. 

PMID- 24300251
TI  - Genomics nursing Faculty Champion initiative.
AB  - Nurse faculty are challenged to keep up with the emerging and fast-paced field of
      genomics and the mandate to prepare the nursing workforce to be able to translate
      genomic research advances into routine clinical care. Using Faculty Champions and
      other options, the initiative stimulated curriculum development and promoted
      genomics curriculum integration. The authors summarize this yearlong initiative
      for undergraduate and graduate nursing faculty. 

PMID- 24300252
TI  - Nurses: where's the caring?
AB  - Nurses have long been known for their compassion and communication with patients.
      Have accelerated nursing programs supported these nursing practice values? In
      this department column, the author explores a troubling trend in recent nursing
      encounters and how one school of nursing is attempting to bring communication
      back to the forefront of nursing education in the accelerated education programs
      and beyond. 

PMID- 24300253
TI  - Implementing a writing course in an online RN-BSN program.
AB  - Scholarly writing is an essential skill for nurses to communicate new research
      and evidence. Written communication directly relates to patient safety and
      quality of care. However, few online RN-BSN programs integrate writing
      instruction into their curricula. Nurses traditionally learn how to write from
      instructor feedback and often not until midway into their baccalaureate
      education. Innovative strategies are needed to help nurses apply critical
      thinking skills to writing. The authors discuss a collaborative project between
      nursing faculty and technical communication faculty to develop and implement a
      writing course that is 1 of the 1st courses the students take in the online RN
      BSN program. 

PMID- 24300254
TI  - Development, evaluation, and utility of a peer evaluation form for online
      teaching.
AB  - Formative assessment of teaching by peers is an important component of quality
      improvement for educators. Teaching portfolios submitted for promotion and tenure
      are expected to include peer evaluations. Faculty resources designed for peer
      evaluation of classroom teaching are often inadequate for evaluating online
      teaching. The authors describe development, evaluation, and utility of a new peer
      evaluation form for formative assessment of online teaching deemed relevant,
      sound, feasible, and beneficial. 

PMID- 24300255
TI  - Improving the process of community-based student nurse practice through a high
      fidelity simulated clinical experience.
AB  - Simulation can be used to facilitate knowledge and practice with clients/families
      in the community. Because student nurses appreciate the opportunity to practice
      skills in a nonthreatening environment, and faculty welcome the opportunity to
      observe all students providing a home visit to a similar type of client, the
      authors developed such a simulation. In this article, they outline the process
      taken to develop and evaluate a high-fidelity community simulated clinical
      experience. 

PMID- 24300256
TI  - Nursing student clinical shift completion as a predictor of NCLEX failure.
AB  - As competition for clinical sites increases, hospitals and nursing schools report
      the use of nontraditional student placements such as one 12-hour clinical shift;
      that was an option offered by the author's school. The author discusses
      implementation of 12-hour shifts and compared NCLEX fail rates of students on one
      12-hour shift with students who had 2 weekly 6-hour shifts. 

PMID- 24300257
TI  - Teaching pathophysiology: strategies to enliven the traditional lecture.
AB  - The depth and breadth of pathophysiology content, foundational for nursing
      practice, is well suited for traditional lecture delivery. Use of creative
      strategies can deepen students' understanding while respecting students' diverse
      talents and ways of learning. The authors discuss strategies they used, including
      case studies, questions asked during lecture using immediate feedback technology,
      creative visual demonstrations, group pathophysiologic theory projects, short
      videos, and games, to enhance students' understanding and retention of content. 

PMID- 24300258
TI  - Avatars in nursing: an integrative review.
AB  - This integrative review explored the use of avatars and virtual worlds in
      education, synthesizing the articles and findings and presenting implications for
      nurse educators. Evaluation of available publications concluded that avatars
      allow students to practice in a safe environment, enhancing learning. The need
      now is for faculty who use avatars and virtual worlds in their teaching to plan
      more robust outcomes assessment that evaluates if the acquired knowledge of
      students, met program objectives, and achieved improved patient outcomes. 

PMID- 24300259
TI  - The coordinator role for a nursing online graduate practicum.
AB  - Although graduate students in nursing are adult learners and expert clinicians,
      they are often novices in the roles they seek upon graduation. Practicum
      experiences help students bridge the gap between theory learned in course work
      and beginning practice at the master's level. However, finding practica for
      online nursing graduate students at great distances is often a challenge. The
      value of having a point person for the coordination of students' practicum
      experiences in multiple settings is well known. What is less well known is how
      this coordination occurs across great distances in online courses that include a
      practicum component. The authors discuss the design and implementation of a
      practicum coordinator position in a graduate online program. 

PMID- 24300260
TI  - Integrating your experience and opportunities to prepare for nurse educator
      certification.
AB  - Certification is accepted as a universal affirmation of expertise. Nurse
      educators validate and demonstrate expertise in nursing education by earning the
      Certified Nurse Educator credential offered through the National League for
      Nursing's Academic Nurse Educator Certification Program. Educators can prepare to
      achieve success in certification by reviewing eligibility requirements, creating
      an individual preparation plan, and using integrated, evidence-based learning
      strategies. 

PMID- 24300261
TI  - [The First Step in a Long-Run-Celebrating the announcement of "Guideline for the
      management of CNS gliomas in China"].

PMID- 24300262
TI  - [Relationship between serum beta2-microglobulin and lower extremity
      atherosclerotic occlusive disease].
AB  - OBJECTIVE: To explore the relationship between fasting serum level of beta2
      microglobulin (beta2-M) and the development of lower extremity atherosclerotic
      occlusive disease (LEAOD). METHODS: A total of 59 LEAOD patients at our hospital
      from March 2011 to August 2012 were recruited into the LEAOD group while another
      32 non-LEAOD patients into the control group. Their clinical profiles and the
      parameters of ankle brachial index (ABI),beta2-M and high-sensitivity C-reactive
      protein (hsCRP) were recorded and analyzed. RESULTS: The patients had higher
      serum levels of beta2-M (5.3 +/- 3.2 vs 2.6 +/- 1.3) and hsCRP (15.1 +/- 14.8 vs
      8.0 +/- 6.7) according to the severity in the LEAOD group than those in the
      control group (P < 0.05).beta2-M was correlated with smoking (beta 1.248, odds
      ratio[OR] 0.020, 95% confidence interval [CI] 1.221-9.942), diabetes (beta
      1.524,OR 4.591, 95%CI 1.493-14.118) and ABI (beta-4.091,OR 0.017, 95%CI 0.002
      0.136) . The receiver operating characteristic (ROC) curve showed that beta2-M
      level had some value of predicting the occurrence of LEAOD (ROCAUC 0.821, 95%CI
      0.731-0.912, P < 0.01). CONCLUSION: Serum level of beta2-M may play a role in
      pathologic process of LEAOD. And further studies are needed to validate its value
      as a biomarker for LEAOD.

PMID- 24300263
TI  - [Efficacy comparison of interventional thrombectomy versus thrombolysis in the
      treatment of acute mixed-type lower extremity deep venous thrombosis].
AB  - OBJECTIVE: To compare the clinical efficacy of interventional thrombectomy versus
      thrombolytic treatment for acute mixed-type lower extremity deep venous
      thrombosis (LEDVT). METHODS: The clinical data of 458 patients with acute mixed
      type LEDVT were analyzed retrospectively.Group A: 327 patients underwent
      mechanical aspiration thrombectomy; Group B: 131 patients received systematic
      thrombolysis and anticoagulation with urokinase and heparin. RESULTS: Complete
      thrombus removal (Grade I): Group A was was better than group B (65.44% vs 37.4%)
      (P = 0.000). The circumference differences of healthy and affected limbs of knee
      joints' below and above 15 cm at discharge were (1.34 +/- 0.57) and (0.93 +/-
      0.32) cm in group A were better than (1.72 +/- 0.69) and (1.29 +/- 0.43) cm in
      group B (both P = 0.000). Among them, 411 patients had a median follow-up period
      of 35 (16-70) and the follow-up rate was 89.83%. At 36 months postoperation, the
      circumference difference of affected limbs of knee-joints' below 15 cm for group
      A (0.53 +/- 0.22) cm was better than that for group B (1.42 +/- 0.65) cm (P =
      0.000) . And the sequelae occurrence rates of edema, pigmentation and ulceration
      of group A (29.64%, 14.01%,0%) were lower than those of group B (55.77%, 83.65%,
      9.62%) (both P = 0.000). Color Doppler flow imaging revealed that the vein
      patency rate of group A was 90.23% and normal valve function rate 71.34%. And
      both were better than group B (37.50%, 15.38%) (P = 0.000; P = 0.000). The total
      effective rate of group A (100%) was better than that of group B (71.15%) (P =
      0.000). Excellency rate: group A (88.93%) was higher than group B (29.81%) (P =
      0.000). CONCLUSION: Interventional thrombectomy is better than simple
      thrombolysis in the treatment of acute mixed-type lower extremity deep venous
      thrombosis. And the former offers better protection of normal valve function.

PMID- 24300264
TI  - [Comparison of cognitive functions and neuropsychiatric symptoms between patients
      with Parkinson's disease dementia and Alzheimer's disease].
AB  - OBJECTIVE: To compare the cognitive functions and neuropsychiatric symptoms of
      Parkinson's disease dementia (PDD) versus Alzheimer's disease (AD). METHODS:
      Patients fulfilling the diagnostic and statistical manual of mental disorders,
      4(th) edition (DSM-IV) dementia diagnosis criteria were recruited into this case
      control study. AD patients were diagnosed with the criteria of National Institute
      of Neurologic and Communicative Disorders and Stroke and Alzheimer's Disease and
      Related Disorders Association (NINCDS-ADRDA) while PDD was based upon the
      standards of Movement Disorder Society (MDS) Task Force. According to clinical
      dementia rating (CDR) score, they were divided into mild dementia (CDR score =
      0.5/1) and moderate-to-severe dementia groups (CDR score = 2/3). World Health
      Organization-University of California, Los Angeles, auditory verbal learning test
      (WHO-UCLA AVLT), clock drawing test (CDT) and neuropsychiatric inventory (NPI)
      were performed. RESULTS: No significant difference in immediate memory, delayed
      memory or long-delayed recognition score was observed between PDD and AD patients
      (P > 0.05). CDT score was significantly lower in PDD patients (mild dementia
      group: 0.9 +/- 0.9; moderate-to-severe dementia group: 0.6 +/- 0.9) than that of
      AD patients (mild dementia group: 1.5 +/- 0.7, P < 0.001; moderate-to-severe
      dementia group: 1.1 +/- 0.6, P = 0.027) and this difference was more significant
      in mild dementia group. More than 70% of PDD patients reported at least one
      neuropsychiatric symptom. And also, in mild dementia group, compared with AD
      patients (frequency: 43.2% (16/37), NPI score = 5.7 +/- 11.9), a higher frequency
      of neuropsychiatric symptoms and higher NPI scores were observed in PDD patients
      (frequency: 71.40% (25/35), NPI score = 8.4 +/- 9.8). CONCLUSION: More severe
      impairment in visuospatial ability and executive function was present in PDD
      patients compared with AD patients. And neuropsychiatric symptoms were more
      common and severe in PDD patients.

PMID- 24300265
TI  - [Relationship between gestational age and apparent diffusion coefficient values
      in different regions of fetal brain from middle to late trimester].
AB  - OBJECTIVE: To analyze the relationship between gestational age and apparent
      diffusion coefficient (ADC) values in different regions of fetal brain from
      middle to late trimester. METHODS: DW images performed in 70 singleton non
      sedated fetuses with questionably abnormal results on sonography and normal fetal
      MR imaging results were retrospectively reviewed. The median gestational age was
      32.4 weeks (range, 24-38).With the formula of ADC = ln (S600/S0)/(B0-B600), the
      mean ADC values were obtained for fetal parietal white matter (WM), frontal WM,
      temporal WM, occipital WM, pons, cerebellum, basal ganglia and thalamus. The
      relationship of mean ADC values in different regions with gestational age was
      analyzed with linear regression. RESULTS: The mean ADC values were 1.77 +/- 0.32
      mm(2)/s (SD) in fetal parietal white matter (WM), 1.71 +/- 0.32 mm(2)/s in
      occipital WM, 1.31 +/- 0.18 mm(2)/s in thalamus, 1.34 +/- 0.15 mm(2)/s in basal
      ganglia. And the mean ADC values in cerebellum, pons, frontal WM and temporal WM
      were 1.17 +/- 0.16, 1.41 +/- 0.18, 1.87 +/- 0.18 and 1.74 +/- 0.19 mm(2)/s
      respectively. A significant negative correlation between ADC values and
      gestational age was found for parietal WM, occipital WM, pons, cerebellum, basal
      ganglia and thalamus (P < 0.05). Frontal WM ADC (P > 0.05) and temporal WM ADC (P
      = 0.05) did not significantly change with gestational age whereas only a downward
      trend was present. The correlation coefficient (r) and coefficient of regression
      (b) were 0.420 and -0.045 in parietal WM; 0.470 and -0.052 in occipital WM; 0.370
      and -0.027 in cerebellum; 0.027 and -0.020 in pons; 0.320 and -0.027 in thalamus;
      0.300 and -0.021 in basal ganglia. The mean ADC values peaked in frontal WM and
      lowest in pons. The mean ADC values in white matter were higher than those in
      deep gray nuclei, cerebellum and pons.With the development of fetal brain,ADC
      values declined the fastest in cerebellum and occipital WM, followed by basal
      ganglia and thalamus. CONCLUSION: Regional differences in non-sedated fetal brain
      ADC values and their evolutions with gestational age are likely to reflect
      variations in brain maturation.

PMID- 24300266
TI  - [Hemodynamic variations during tracheal intubation with intubating laryngeal mask
      airway versus direct laryngoscope in hypertensive patients].
AB  - OBJECTIVE: To compare the variations of cardiovascular responses and vascular
      angiotensin II (AngII) in hypertensive patients during tracheal intubation with
      intubating laryngeal mask airway (ILMA) versus direct laryngoscope (DLS).
      METHODS: A total of 120 hypertensive patients undergoing abdominal surgery were
      randomly divided into 2 groups, i.e.intubating laryngeal mask airway (Group I)
      and direct laryngoscope (Group D).Variations of invasive arterial blood pressure
      and angiotensin II were compared between two groups before and after intubation.
      RESULTS: The variations of cardiovascular responses and vascular angiotensin II
      (AngII) during tracheal intubation used of ILMA (T4) and DLS (T4) in an instant,
      tracheal intubation were immediately accomplished in two groups (T5). The
      variations of group I were significantly lower than those of group D (P < 0.05).
      And statistical significance existed between two groups. CONCLUSION: Tracheal
      intubation with intubating laryngeal mask airway (ILMA) can significantly reduce
      violent cardiovascular reactions and avoid cardiovascular accidents.

PMID- 24300267
TI  - [Etiology and treatment of postoperative spinal cord injury for patients
      undergoing laminectomy for fluorosis thoracic canal stenosis].
AB  - OBJECTIVE: To elucidate the etiology of postoperative spinal cord injury (PSCI)
      for patients undergoing laminectomy for fluorosis thoracic canal stenosis (FTCS)
      and summarize the methods of diagnosis and treatment. METHODS: From 2006 to 2009,
      a total of 192 FTCS cases underwent laminectomy. Among them, 16 cases with
      gradual postoperative neural deterioration were finally diagnosed as PSCI on
      MRI.One case of intraoperative spinal cord injury was excluded so that only 15
      cases were included. RESULTS: All cases were treated immediately with incision
      cite puncture and dehydration.Neural function recovered after secondary operation
      as JOA score improved from 3.00 +/- 1.14 to 7.72 +/- 1.41 at 12 months follow
      up.Statistical analysis demonstrated a linear correlation between the diagnosis
      time and the improvement of JOA score. CONCLUSION: Hematoma and fluid leakage are
      the common reasons of PSCI for FTCS patients. Meticulous hemostasis, usage of
      artificial dura matter and partial negative pressure drainage are valuable
      preventive measures.

PMID- 24300268
TI  - [Autophagy expression and its significance in chondrocytes from a degenerate
      model of human cervical endplate].
AB  - OBJECTIVE: To explore the autophagy expression and examine its significance in
      chondrocytes in a degenerate model of human cervical vertebrae endplate. METHODS:
      Cartilage endplates were obtained from 48 hospitalized patients with cervical
      vertebral fracture or dislocation at our hospital between February 2012 to August
      2012. They were divided into cervical spondylosis group with cervical spondylotic
      myelopathy (n = 31) and control group (n = 17).Endplate chondrocytes were
      isolated by enzyme digestion and cultured in vitro. The cells were stained with
      toluidine blue and hematoxylin and eosin; laser scanning confocal microscope and
      monodansylcadaverine (MDC) were used to observe autophagy in endplate
      chondrocytes; reverse transcription-polymerase chain reaction (RT-PCR) was used
      to detect the mRNA expression of typeIIcollagen and aggrecan and Western blot for
      the protein of LC3. RESULTS: A degenerative cell model of human cervical endplate
      chondrocytes was established successfully in vitro. Compared with the common
      group, the cellular morphologies of degenerative group showed spindle changes.
      Autophagic body was stained with MDC.Intracellular and perinuclear LC3 protein
      was detected by laser confocal microscopy. Compared with the control group, the
      mRNA expressions of aggrecan (0.715 +/- 0.194) and typeII collagen (0.628 +/-
      0.254) markedly decreased (0.845 +/- 0.186,0.913 +/- 0.254, P < 0.05) and LC3
      II/LC3-I declined in cervical spondylosis group. CONCLUSION: Autophagy plays an
      important pathogenic role in the process of human cervical disc degeneration. And
      regulating its expression may improve disc degeneration in endplate cartilage
      cells.

PMID- 24300269
TI  - [Establishment of Schatzker classification digital models of tibial plateau
      fractures and its application on virtual surgery].
AB  - OBJECTIVE: To explore the establishment of Schatzker classification digital model
      of tibial plateau fractures and its application in virtual surgery. METHODS:
      Proximal tibial of one healthy male volunteer was examined with 64-slice spiral
      computed tomography (CT). The data were processed by software Mimics 10.01 and a
      model of proximal tibia was reconstructed. According to the Schatzker
      classification criteria of tibial plateau fractures, each type of fracture model
      was simulated.Screen-captures of fracture model were saved from different
      directions.Each type of fracture model was exported as video mode.Fracture model
      was imported into FreeForm modeling system.With a force feedback device, a
      surgeon could conduct virtual fracture operation simulation.Utilizing the GHOST
      of FreeForm modeling system, the software of virtual cutting, fracture reduction
      and fixation was developed.With a force feedback device PHANTOM, a surgeon could
      manipulate virtual surgical instruments and fracture classification model and
      simulate surgical actions such as assembly of surgical instruments, drilling,
      implantation of screw, reduction of fracture, bone grafting and fracture
      fixation, etc. RESULTS: The digital fracture model was intuitive, three
      dimensional and realistic and it had excellent visual effect.Fracture could be
      observed and charted from optional direction and angle.Fracture model could
      rotate 360  degrees  in the corresponding video mode. The virtual surgical
      environment had a strong sense of reality, immersion and telepresence as well as
      good interaction and force feedback function in the FreeForm modeling system. The
      user could make the corresponding decisions about surgical method and choice of
      internal fixation according to the specific type of tibial plateau fracture as
      well as repeated operational practice in virtual surgery system. CONCLUSION: The
      digital fracture model of Schatzker classification is intuitive, three
      dimensional, realistic and dynamic. The virtual surgery systems of Schatzker
      classifications make the virtual surgery training more normalized, programmed and
      standardized.In addition, virtual surgery system can serve as a new tool for
      preoperative planning and surgeon-patient interactions.

PMID- 24300270
TI  - [Role of transcription factor ETS-1 and B cell in the pathogenesis of systemic
      lupus erythematosus].
AB  - OBJECTIVE: To explore the effects of transcription factor ETS-1 mRNA and B
      lymphocyte-associated cytokines on the differentiation of B cells in systemic
      lupus erythematosus (SLE) patients and explore its pathogenic and clinical
      significance. METHODS: Thirty-one SLE patients (20 active and 11 inactive) and 15
      healthy controls were enrolled. CD19+ B cells were isolated with magnetic beads.
      The levels of ETS-1 mRNA in B cells were determined by real-time polymerase chain
      reaction (PCR). Flow cytometry was used to detect the altered ratio of CD19-CD138
      + plasma cells and CD19 + B cells. And enzyme-linked immunosorbent assay (ELISA)
      was performed to detect the serum levels of B cell differentiation-related
      cytokines interleukin-10 (IL-10) and APRIL. RESULTS: Compared to the healthy
      controls, SLE patients showed decreased mRNA expression level of ETS-1 in B cells
      (Z = -4.218, P < 0.01) . Moreover, the expression level of ETS-1 mRNA was
      significantly negatively correlated with the proportion of CD19-CD138+ plasma
      cells (r = -0.359, P < 0.05) and negatively correlated with the CD19-CD138 +B
      cells/CD19+ plasma cells ratio (r = -0.493, P < 0.01) . However, there was no
      correlation in normal controls. Significant negative correlation existed between
      the expression level of ETS-1 mRNA in B cells and the serum levels of IL-10 and
      APRIL in active SLE patients. But no correlation existed in inactive group.
      CONCLUSION: ETS-1 may participate in the pathogenesis of SLE through its effects
      on the differentiation of B cells and cooperation with IL-10 and APRIL.

PMID- 24300271
TI  - [Value of serum ferritin in measuring the activation and prognosis in systemic
      onset juvenile idiopathic arthritis].
AB  - OBJECTIVE: To explore the correlation of serum ferritin (SF) and systemic onset
      juvenile idiopathic arthritis (SOJIA) so as to determine the prognostic values of
      SF for SOJIA. METHODS: All samples were collected from 92 juvenile idiopathic
      arthritis (JIA) patients at Beijing Children's Hospital between February 2005 to
      September 2012. Their age range was 2-15 years. There were macrophage activation
      syndrome (MAS, n = 25), polyarticular JIA (n = 33) and oligoarticular JIA (n =
      30). And 47 healthy children and another 30 with acute infective diseases were
      selected as control groups respectively. Blood samples were collected and SF was
      measured in different disease phases.Other parameters include leucocyte,
      hemoglobin, platelet, C-reactive protein and erythrocyte sedimentation
      rate.Statistics of SF level at different groups as well as at different disease
      phases were performed. RESULTS: The SF level of active phase SOJIA patients was
      significantly higher (P < 0.01) than that in Other groups. And its level in the
      active phase of SOJIA was significantly higher than that in patients during the
      recovery phase. The SF level in patients with MAS was significantly higher than
      that in those without MAS. CONCLUSION: Correlated with the course of SOJIA, the
      level of SF may judge the disease activity and predict the outcomes of SOJIA.

PMID- 24300272
TI  - [Clinical efficacy and safety of megestrol acetate vaginal ring].
AB  - OBJECTIVE: To explore the efficacy and safety of megestrol acetate silicone
      vaginal ring. METHODS: A total of 165 healthy child-bearing age women were
      recruited to examine the efficacy, safety and satisfaction rate of megestrol
      acetate silicone vaginal ring. RESULTS: The cumulative pregnancy rate of
      megestrol acetate silicone vaginal ring was 3.93%. And its discontinuation rate
      was 2.54%, the incidence of adverse events 11.52% and the incidence of adverse
      effects 1.81% while the symptoms were all slight. The bleeding pattern was
      similar to that of normal menstruation. Compared with baseline, the elevated
      level of triglycerides and the reduced level of low-density lipoprotein (LDL)
      were significantly different while no significant difference existed in high
      density lipoprotein (HDL), cholesterol and hemoglobin, etc. The satisfaction rate
      of megestrol acetate silicone vaginal ring was 94.6% and increased with time.
      CONCLUSION: Megestrol acetate silicone vaginal ring is an effective and safe
      option of contraceptives.

PMID- 24300273
TI  - [Relationship between the expression of dual specificity phosphatase-1 and the
      prognosis of endometrioid adenocarcinoma].
AB  - OBJECTIVE: To clarify the relationship between the expression of dual specificity
      phosphatase-1 (DUSP1) and the prognosis of endometrioid adenocarcinoma. METHODS:
      The expression of DUSP1 was determined by immunohistochemical staining in
      specimens from 81 patients with endometrial carcinoma undergoing surgical
      resection. The relationship between DUSP1 expression, clinicopathological factors
      and prognosis were further evaluated. RESULTS: In 81 endometrioid carcinoma
      samples, 59 (72.84%) cases were positive while 22 negative.Except for lymph node
      metastasis, the expression of DUSP1 was correlated with FIGO stage, tumor grade,
      myometrial invasion and the expressions of estrogen receptor (ER) and
      progesterone receptor (PR) (P < 0.05) .Kaplan-Meier analysis showed that patients
      with a positive DUSP1 expression had significantly prolonged 5-year disease-free
      survival rates of 98.2% and 76.0% respectively (P < 0.05). And COX regression
      analysis revealed that the expressions of DUSP1 and PR were independent
      prognostic indicators of endometrioid carcinoma, the HR (hazard ratio) of DUSP1
      negative expression was 21.2.Spearman analysis further showed that the expression
      of DUSP1 was positively correlated with PR (r = 0.256, P < 0.05). CONCLUSION:
      DUSP1 may be a potential negative prognostic indicator for endometrioid
      adenocarcinoma.

PMID- 24300274
TI  - [Differential judgment of coronary stenosis by 320-slice dynamic volume computed
      tomography and coronary angiography].
AB  - OBJECTIVE: To compare the characteristics of lesions with consistent and
      inconsistent judgments of coronary stenosis on 320-slice dynamic volume computed
      tomography (DVCT) versus coronary angiography (CAG). METHODS: Ninety-two patients
      (265 lesions) with CAG and DVCT within 2 weeks from January 2011 to May 2012 were
      enrolled. According to the matching degree of stenotic judgment, all lesions were
      divided into consistent and inconsistent groups. The position of lesions, degree
      of bending, plaque morphology and calcification proportion were analyzed.
      RESULTS: There were 236 lesions in consistent group versus 29 lesions in
      inconsistent group.In inconsistent group, there were more left circumflex artery,
      distal, ostial and tortuous lesions than that in consistent group (P < 0.05). At
      the same time, the proportion of nubbly type plaque, calcified plaque, nubbly and
      nodular type calcification in the main plaque in inconsistent group was higher
      than those in consistent group (P < 0.05).Segmental coronary calcium score (250
      +/- 210 vs 82 +/- 66, P < 0.05), number of calcifications and calcification
      proportion in main plaque (55% +/- 28% vs 43% +/- 30%, P < 0.05) in inconsistent
      group were higher than those in consistent group (P < 0.05). CONCLUSION: When
      coronary lesion occurs in ostial, distal or tortuous position or its main plaque
      is of nubbly type with a heavy calcification load, the judgment of stenosis by
      CTA and CAG is more likely to be inconsistent.

PMID- 24300275
TI  - [Expression pattern of inflammatory cytokines at various inflammatory levels of
      adamantinomatous craniopharyngioma].
AB  - OBJECTIVE: To explore the expression pattern of inflammatory cytokines at various
      inflammatory levels of adamantinomatous craniopharyngioma by cytokine antibody
      array. METHODS: The inflammatory levels of adamantinomatous craniopharyngioma
      were evaluated on the basis of the number of inflammatory cells at the interface
      of tumor and normal tissues. And the expression of inflammatory cytokines was
      examined at various inflammatory levels of adamantinomatous craniopharyngioma by
      inflammatory cytokine antibody array and the results were verified by Western
      blot. RESULTS: Compared with the mild inflammatory group, the levels of
      inflammatory cytokines of severe inflammatory group markedly increased, including
      pro-inflammatory cytokines, chemokines and cytokine receptors. CONCLUSION:
      Antibody array demonstrates a significant change in cytokine profiles in
      adamantinomatous craniopharyngioma with severe inflammation, as compared with
      those with mild inflammation.

PMID- 24300276
TI  - [Clinical research on surgical treatment for non-small cell lung cancer of
      diameter less than 2 cm].
AB  - OBJECTIVE: To discuss the model of reasonable dissection extent of mediastinal
      lymph nodes in non-small cell lung cancer of diameter less than 2 cm. METHOD: A
      study was carried on the clinical data of 192 patients with NSCLC of diameter
      less than 2 cm undergoing curative resection and mediastinal lymph nodes
      dissection,According to the size of tumor and the pathology quick report.
      RESULTS: The survival rates of patient was statistically significant difference
      (P < 0.01), prognostic factors included diameter of tumor, lymph node metastasis
      and visceral pleura invasion;51.7% mediastinal lymph node metastasis of superior
      lobe tumor, 28.8% transfering to subcarinal node; the mediastinal lymph node
      metastasis rate of adenocarcinoma was 32.2%, and squamous cell carcinoma was
      15.4% (P = 0.0012) . CONCLUSION: If the patient's cardiopulmonary function
      permitting, regardless of the size of focus, Regional mediastinal lymph nodal and
      subcarinal lymph nodal dissection should be routinely performed on patients with
      non-small cell lung cancer of diameter less than 2 cm, and improve survival rate.

PMID- 24300277
TI  - [Expression and diagnosis value of Fascin in non-small cell lung cancer
      patients].
AB  - OBJECTIVE: To evaluate the diagnostic significance of Fascin protein in non-small
      cell lung cancer (NSCLC) patients. METHODS: Among 110 cases of NSCLC patients and
      50 cases of healthy controls, double antibody sandwich enzyme-linked
      immunosorbent assay (ELISA) was employed to measure the serum levels of Fascin
      protein, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), scales
      like squamous cell carcinoma (SCC) antigen, cytokeratin protein 21-1 (CYFRA21-1)
      and gastrin-releasing peptide (GRP) precursor. Fascin-positive rate (24.4%) in
      NSCLC patients was significantly higher than that in healthy controls (4%) (P <
      0.05).In different clinical stages of non-small cell lung cancer patients, Fascin
      positive rate was statistically significant (P < 0.05). The positive rates of
      Fascin for CEA, CYFRA21-1, NSE, SCC and Pro-GRP were 25.64%, 5.1%, 5.1%, 5.0% and
      1.7% respectively. CONCLUSION: As a new tumor marker, Fascin may be used for
      clinical screening and prognosis in lung cancer.

PMID- 24300278
TI  - [Anti-N-methyl-D-aspartic acid receptor encephalitis: clinical analysis of 7
      cases].
AB  - OBJECTIVE: To summarize the clinical manifestations, immunotherapeutic response
      and prognosis of anti-N-methyl-D-aspartic acid (NMDA) receptor encephalitis.
      METHODS: We analyzed the clinical features, tumor markers, serum/cerebrospinal
      fluid (CSF) antibodies of seven cases with anti-NMDA receptor encephalitis. And
      the prognosis of different treatments was observed. RESULTS: Seven patients
      presented with significant psychiatric symptoms, memory loss, epilepsy, movement
      disorders and decrease consciousness. And some patients required assisted
      ventilation because of dysautonomia. All electroencephalography showed slow wave
      activity without epileptic form discharges. Magnetic resonance imaging was normal
      or showed T2W and Flair-phase high signal in limbic system, cortex, thalamus. And
      CSF and serum anti-NMDA receptor antibodies were positive (n = 6). CONCLUSION:
      Anti-NMDA receptor encephalitis is a kind of fatal but treatable condition. And
      timely diagnosis and treatment may yield a favorable prognosis.

PMID- 24300279
TI  - [Construction of recombinant lentiviral vector containing integrin beta1 shRNA
      and its effects on integrin beta1 gene expression in Sombati cell culture model
      of refractory epilepsy].
AB  - OBJECTIVE: To construct a recombinant lentiviral vector containing integrin beta1
      shRNA to provide an effective tool for integrin beta1 gene effect and a possible
      mechanism of Sombati cell of clinical refractory epilepsy. METHODS: Four
      lentiviral vectors containing integrin beta1 shRNA were constructed and
      transfected into 293T cells. PC12 cells were infected by concentrated lentivirus
      and the gene-silencing efficiency was verified. And the most effective lentivirus
      containing shRNA was selected with Western blot. Then neonatal rat hippocampal
      neurons and Sombati cells were infected by lentivirus containing shRNA and the
      gene-silencing efficiency was also monitored by Western blot. RESULTS: RNAi
      lentivirus expression vectors targeting rat integrin beta1 gene were successfully
      constructed and confirmed by DNA sequencing. The recombinant lentivirus particles
      were packaged successfully to produce a sufficient titer for subsequent
      experiments. The expression of protein significantly decreased in rat hippocampal
      neurons and rat Sombati cells after vector transfection. CONCLUSION: The
      recombinant lentiviral vector containing integrin beta1 shRNA is constructed
      successfully. And the gene-silencing effects are effective and stable in neonatal
      rat hippocampal neurons and Sombati cells.

PMID- 24300281
TI  - Electrophysiological recording in the brain of intact adult zebrafish.
AB  - Previously, electrophysiological studies in adult zebrafish have been limited to
      slice preparations or to eye cup preparations and electrorentinogram recordings.
      This paper describes how an adult zebrafish can be immobilized, intubated, and
      used for in vivo electrophysiological experiments, allowing recording of neural
      activity. Immobilization of the adult requires a mechanism to deliver dissolved
      oxygen to the gills in lieu of buccal and opercular movement. With our technique,
      animals are immobilized and perfused with habitat water to fulfill this
      requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222;
      tricaine) anesthesia to provide access to the brain. The primary electrode is
      then positioned within the craniotomy window to record extracellular brain
      activity. Through the use of a multitube perfusion system, a variety of
      pharmacological compounds can be administered to the adult fish and any
      alterations in the neural activity can be observed. The methodology not only
      allows for observations to be made regarding changes in neurological activity,
      but it also allows for comparisons to be made between larval and adult zebrafish.
      This gives researchers the ability to identify the alterations in neurological
      activity due to the introduction of various compounds at different life stages. 

PMID- 24300280
TI  - Cardiolipin asymmetry, oxidation and signaling.
AB  - Cardiolipins (CLs) are ancient and unusual dimeric phospholipids localized in the
      plasma membrane of bacteria and in the inner mitochondrial membrane of
      eukaryotes. In mitochondria, two types of asymmetries--trans-membrane and
      molecular--are essential determinants of CL functions. In this review, we
      describe CL-based signaling mitochondrial pathways realized via modulation of
      trans-membrane asymmetry and leading to externalization and peroxidation of CLs
      in mitophagy and apoptosis, respectively. We discuss possible mechanisms of CL
      translocations from the inner leaflet of the inner to the outer leaflet of the
      outer mitochondrial membranes. We present redox reaction mechanisms of cytochrome
      c-catalyzed CL peroxidation as a required stage in the execution of apoptosis. We
      also emphasize the significance of CL-related metabolic pathways as new targets
      for drug discovery. Finally, a remarkable diversity of polyunsaturated CL species
      and their oxidation products have evolved in eukaryotes vs. prokaryotes. This
      diversity--associated with CL molecular asymmetry--is presented as the basis for
      mitochondrial communications language.

PMID- 24300282
TI  - Ageing, immunity and influenza: a role for probiotics?
AB  - Influenza is a major cause of death in the over 65s. Increased susceptibility to
      infection and reduced response to vaccination are due to immunosenscence in
      combination with medical history and lifestyle factors. Age-related alterations
      in the composition of the gut microbiota have a direct impact on the immune
      system and it is proposed that modulation of the gut microbiota using pre- and
      probiotics could offer an opportunity to improve immune responses to infections
      and vaccination in older people. There is growing evidence that probiotics have
      immunomodulatory properties, which to some extent are strain-dependent, and are
      strongly influenced by ageing. Randomised controlled trials suggest that
      probiotics may reduce the incidence and/or severity of respiratory infections,
      although there is limited data on older people. A small number of studies have
      examined the potential adjuvant effects of selected probiotics for vaccination
      against influenza; however, the data is inconsistent, particularly in older
      people. This review describes the impact of age-related changes in the gut on the
      immune response to respiratory infections and evaluates whether restoration of
      gut microbial homoeostasis by probiotics offers an opportunity to modulate the
      outcome of respiratory infections and vaccination against influenza in older
      people. Although there is promising evidence for effects of probiotics on human
      health, there is a lack of consistent data, perhaps partly due to strain-specific
      differences and an influence of the age of the host. Further research is critical
      in evaluating the potential use of probiotics in respiratory infections and
      vaccination in the ageing population. 

PMID- 24300284
TI  - Risk prediction in sexual health contexts: protocol.
AB  - BACKGROUND: In British Columbia (BC), we are developing Get Checked Online (GCO),
      an Internet-based testing program that provides Web-based access to sexually
      transmitted infections (STI) testing. Much is still unknown about how to
      implement risk assessment and recommend tests in Web-based settings. Prediction
      tools have been shown to successfully increase efficiency and cost-effectiveness
      of STI case finding in the following settings. OBJECTIVE: This project was
      designed with three main objectives: (1) to derive a risk prediction rule for
      screening chlamydia and gonorrhea among clients attending two public sexual
      health clinics between 2000 and 2006 in Vancouver, BC, (2) to assess the temporal
      generalizability of the prediction rule among more recent visits in the Vancouver
      clinics (2007-2012), and (3) to assess the geographical generalizability of the
      rule in seven additional clinics in BC. METHODS: This study is a population
      based, cross-sectional analysis of electronic records of visits collected at nine
      publicly funded STI clinics in BC between 2000 and 2012. We will derive a risk
      score from the multivariate logistic regression of clinic visit data between 2000
      and 2006 at two clinics in Vancouver using newly diagnosed chlamydia and
      gonorrhea infections as the outcome. The area under the receiver operating
      characteristic curve (AUC) and the Hosmer-Lemeshow statistic will examine the
      model's discrimination and calibration, respectively. We will also examine the
      sensitivity and proportion of patients that would need to be screened at
      different cutoffs of the risk score. Temporal and geographical validation will be
      assessed using patient visit data from more recent visits (2007-2012) at the
      Vancouver clinics and at clinics in the rest of BC, respectively. Statistical
      analyses will be performed using SAS, version 9.3. RESULTS: This is an ongoing
      research project with initial results expected in 2014. CONCLUSIONS: The results
      from this research will have important implications for scaling up of Internet
      based testing in BC. If a prediction rule with good calibration, discrimination,
      and high sensitivity to detect infection is found during this project, the
      prediction rule could be programmed into GCO so that the program offers
      individualized testing recommendations to clients. Further, the prediction rule
      could be adapted into educational materials to inform other Web-based content by
      creating awareness about STI risk factors, which may stimulate health care
      seeking behavior among individuals accessing the website.

PMID- 24300283
TI  - Interactive effects of in vitro binge-like alcohol and ATP on umbilical
      endothelial nitric oxide synthase post-translational modifications and redox
      modulation.
AB  - Alcohol dysregulates the regulation of reproductive vascular adaptations. We
      herein investigated chronic in vitro binge-like alcohol effects on umbilical
      endothelial nitric oxide synthase (eNOS) multi-site phosphorylation and related
      redox switches under basal (unstimulated) and stimulated (with ATP) states.
      Alcohol decreased endothelial excitatory (Pser1177)eNOS (P<0.001), whereas
      excitatory (Pser635)eNOS exhibited a main effect of alcohol (?P=0.016) and ATP
      (?P<0.001). Alcohol decreased (Pthr495)eNOS (P=0.004) levels, whereas inhibitory
      (Pser116)eNOS exhibited an alcohol main effect in both basal and stimulated
      states (?P=0.005). Total eNOS was reduced by alcohol (P=0.038). In presence of
      ATP, alcohol inhibited ERK activity (P=0.002), whereas AKT exhibited no alcohol
      effect. Alcohol main effect on S-nitroso-glutathione reductase (?P=0.031) and
      glutathione-S-transferase (?P=0.027) were noted. Increased protein
      glutathiolation was noted, whereas no alcohol effect on GSH, GSSG, NOX2 or SOD
      expression was noted. Thus, alcohol effects on multi-site post-translational
      modifications and redox switches related to vasodilatory eNOS underscore the
      necessity for investigating alcohol-induced gestational vascular dysfunction. 

PMID- 24300286
TI  - Historical records of organic pollutants in sediment cores.
AB  - Analyses of sediment core samples are primary sources of historical pollution
      trends in aquatic systems. Determining organic compounds, such as POPs, in the
      dated sediments enables the estimation of their temporal concentration changes
      and the identification of the contaminant origin in local regions. Wars, large
      scale fires, economical transitions, and bans on certain chemicals are reflected
      in the sediment organic compound concentrations. The high POP concentrations in
      surficial sediments suggest that these chemicals, even after being banned, remain
      in the environment. Furthermore, vertical profiles can help in understanding the
      sedimentation process and in estimating effective countermeasures against
      pollution. Moreover, studies published during the period 1991-2013 on PAHs, PCBs,
      OCPs, dioxins and dioxin-like compound concentrations in sediment core samples
      are reviewed. 

PMID- 24300285
TI  - A microplate assay to assess chemical effects on RBL-2H3 mast cell degranulation:
      effects of triclosan without use of an organic solvent.
AB  - Mast cells play important roles in allergic disease and immune defense against
      parasites. Once activated (e.g. by an allergen), they degranulate, a process that
      results in the exocytosis of allergic mediators. Modulation of mast cell
      degranulation by drugs and toxicants may have positive or adverse effects on
      human health. Mast cell function has been dissected in detail with the use of rat
      basophilic leukemia mast cells (RBL-2H3), a widely accepted model of human
      mucosal mast cells(3-5). Mast cell granule component and the allergic mediator
      beta-hexosaminidase, which is released linearly in tandem with histamine from
      mast cells(6), can easily and reliably be measured through reaction with a
      fluorogenic substrate, yielding measurable fluorescence intensity in a microplate
      assay that is amenable to high-throughput studies(1). Originally published by
      Naal et al.(1), we have adapted this degranulation assay for the screening of
      drugs and toxicants and demonstrate its use here. Triclosan is a broad-spectrum
      antibacterial agent that is present in many consumer products and has been found
      to be a therapeutic aid in human allergic skin disease(7-11), although the
      mechanism for this effect is unknown. Here we demonstrate an assay for the effect
      of triclosan on mast cell degranulation. We recently showed that triclosan
      strongly affects mast cell function(2). In an effort to avoid use of an organic
      solvent, triclosan is dissolved directly into aqueous buffer with heat and
      stirring, and resultant concentration is confirmed using UV-Vis spectrophotometry
      (using epsilon280 = 4,200 L/M/cm)(12). This protocol has the potential to be used
      with a variety of chemicals to determine their effects on mast cell
      degranulation, and more broadly, their allergic potential. 

PMID- 24300287
TI  - Distributions of polychlorinated biphenyls in the Daliao River estuary of
      Liaodong Bay, Bohai Sea (China).
AB  - The distributions of 41 polychlorinated biphenyls (PCBs) were determined in the
      aqueous phase, suspended particulate matter (SPM), and sediment of the Daliao
      River estuary in Liaodong Bay, Bohai Sea (China). The total PCB concentrations
      ranged from 5.51 to 40.28 ng L(-1) in the surface water, from 6.78 to 66.55 ng L(
      1) dry weight in the SPM, and from 0.83 to 7.29 ng g(-1) dry weight in the
      sediment. The PCB concentrations in water, SPM, and sediment were moderate
      relative to those reported for other estuary and marine systems around the world.
      Sedimentary PCB concentrations decreased offshore due to the active deposition of
      laterally transported river-borne particles. The predominance of the highly
      chlorinated congeners for the water, SPM, and sediment samples are an indication
      of either a lack of degradation or the presence of nearby or recent releases into
      the environment.

PMID- 24300288
TI  - A novel frameshift mutation and infrequent clinical findings in two cases with
      Dyggve-Melchior-Clausen syndrome.
AB  - Dyggve-Melchior-Clausen syndrome (DMC) (MIM #223800) is a rare autosomal
      recessive type of skeletal dysplasia accompanied by variable degrees of
      intellectual disability (ID). It is characterized by progressive
      spondyloepimetaphyseal dysplasia leading to disproportionate short stature,
      microcephaly, and coarse facies. The radiographic appearance of generalized
      platyspondyly with double-humped end plates and the lace-like appearance of iliac
      crests are pathognomonic in this syndrome. The disorder results from mutations in
      the dymeclin (DYM) mapped to the 18q12-12.1 chromosomal region. Here, we report
      two cases with DMC: one with disproportionate short stature, developmental delay,
      and severe ID with a novel frameshift mutation (c.1028_1056del29) leading to a
      premature stop codon, and the second patient with classical clinical and
      radiological features of DMC with mild ID and rectal prolapse, which is very
      rare. The clinical diagnosis was confirmed with molecular analysis of DYM with a
      known mutation at c.580C>T (p.R194X). The parents and sibling of the second
      patient were heterozygous carriers with mild skeletal changes and short stature. 

PMID- 24300289
TI  - The postnatal features of bent bone dysplasia-FGFR2 type.

PMID- 24300290
TI  - Craniosynostosis: a previously unreported association with CHST3-related skeletal
      dysplasia (autosomal recessive Larsen syndrome).

PMID- 24300291
TI  - Mowat-Wilson syndrome associated with craniosynostosis.

PMID- 24300292
TI  - Interstitial 3p25 deletion in a patient with features of 3p deletion syndrome:
      further evidence for the role of SRGAP3 in mental retardation.

PMID- 24300293
TI  - Hypopigmented skin patches in 17q21.31 microdeletion syndrome: expanding the
      spectrum of cutaneous findings.

PMID- 24300294
TI  - Development and validation of a successful microbiological agar assay for
      determination of ceftriaxone sodium in powder for injectable solution.
AB  - Ceftriaxone sodium is a cephalosporin with broad-spectrum antimicrobial activity
      and belongs to the third generation of cephalosporins. Regarding the quality
      control of medicines, a validated microbiological assay for the determination of
      ceftriaxone sodium in powder for injectable solution has not been reported yet.
      This paper reports the development and validation of a simple, accurate and
      reproducible agar diffusion method to quantify ceftriaxone sodium in powder for
      injectable solution. The assay is based on the inhibitory effect of ceftriaxone
      sodium on the strain of Bacillus subtilis ATCC 9371 IAL 1027 used as test
      microorganism. The results were treated statistically by analysis of variance and
      were found to be linear (r = 0.999) in the selected range of 15.0-60.0 MUg/mL,
      precise with a relative standard deviation (RSD) of repeatability intraday =
      1.40%, accurate (100.46%) and robust with a RSD lower than 1.28%. The results
      demonstrated the validity of the proposed bioassay, which allows reliable
      ceftriaxone sodium quantitation in pharmaceutical samples and therefore can be
      used as a useful alternative methodology for the routine quality control of this
      medicine. 

PMID- 24300295
TI  - Design of skin penetration enhancers using replacement methods for the selection
      of the molecular descriptors.
AB  - Transdermal delivery of certain drugs is challenging because of skin barrier
      resistance. This study focuses on the implementation of feature-selection
      algorithms to design chemical penetration enhancers. A database, consisting of
      145 polar and nonpolar chemicals, was chosen for the investigation. Replacement,
      enhanced replacement and stepwise algorithms were applied to identify relevant
      structural properties of these compounds. The descriptors were calculated using
      Molecular Modeling ProTM Plus. Based on the coefficient of determination, the
      replacement methods outperformed the stepwise approach in selecting the features
      that best correlated with the flux enhancement ratio. An artificial neural
      network model was built to map a subset of descriptors from sixty-one nonpolar
      enhancers onto the output vector. The R2 value improved from 0.68, for a linear
      model, to 0.74, which shows that the improved framework might be effective in the
      design of compounds with user-defined properties. 

PMID- 24300296
TI  - Application and Characterization of Gum from Bombax buonopozense Calyxes as an
      Excipient in Tablet Formulation.
AB  - This study was undertaken to explore gum from Bombax buonopozense calyxes as a
      binding agent in formulation of immediate release dosage forms using wet
      granulation method. The granules were characterized to assess the flow and
      compression properties and when compressed, non-compendial and compendial tests
      were undertaken to assess the tablet properties for tablets prepared with bombax
      gum in comparison with those prepared with tragacanth and acacia gums. Granules
      prepared with bombax exhibited good flow and compressible properties with angle
      of repose 28.60 degrees , Carr's compressibility of 21.30% and Hausner's quotient
      of 1.27. The tablets were hard, but did not disintegrate after one hour.
      Furthermore, only 52.5% of paracetamol was released after one hour. The drug
      release profile followed zero order kinetics. Tablets prepared with bombax gum
      have the potential to deliver drugs in a controlled manner over a prolonged
      period at a constant rate. 

PMID- 24300297
TI  - Using ion-selective electrodes to study the drug release from porous cellulose
      matrices.
AB  - Polyvinyl chloride (PVC)-based solid-contact ion-selective electrodes (SC-ISEs),
      responding to propranolol hydrochloride (Pr+) and lidocaine hydrochloride (Ld+)
      cations as the model drugs with potassium tetrakis(4-chlorophenyl) borate
      (KTpClPB) as the ion exchanger, were studied. Different drug-polymer solutions
      were prepared with the model drugs, using different blend ratios of
      ethylcellulose (EC) and hydroxypropyl cellulose (HPC). Two different solid dosage
      forms were used. Polymer films were produced by solvent casting method and drug
      containing porous cellulose samples were prepared by depositing the drug-polymer
      solutions onto filter paper substrates. The quality of the electrodes and the
      release profile of Pr+ and Ld+ were investigated with the potentiometric method.
      The results were compared to UV spectrophotometry. The electrodes were found to
      be sensitive, precise and functional with a Nernstian behavior over the range of
      1.0 * 10-3-3.1 * 10-6 M (9.2 * 10-4-3.0 * 10-1 mg/mL) and 1 * 10-3-2 * 10-6 M
      (5.4 * 10-4-2.7 * 10-1 mg/mL) at 25  degrees C for Pr+ and Ld+ sensitive
      electrodes, respectively. The dynamic response time for the electrodes was less
      than 10 s. The Pr+ release from porous filter paper was always higher than its
      equivalent film formulation. Also, lidocaine had higher and faster release from
      the samples with higher drug concentration. The comparison of the two analytical
      methods showed near identical results. The ISEs provided a powerful and flexible
      alternative to UV method in determination of drug release from porous cellulose
      substrates in a small scale dissolution testing. 

PMID- 24300298
TI  - The Effect of Diluted Penetration Enhancer in Nebulized Mist versus Liquid Drop
      Preparation Forms on Retrobulbar Blood Flow in Healthy Human Subjects.
AB  - The aim of this study was to compare the effects of nebulized mist and liquid
      drop applications on retrobulbar blood flow. A prospective, non-randomized
      clinical trial was used to collect data from 40 healthy human eyes. Color Doppler
      Imaging determined peak systolic (PSV) and end diastolic (EDV) blood flow
      velocities and resistance index (RI) in the ophthalmic artery after both
      applications. Measurements were taken at baseline and at 1 min post-treatment in
      both eyes with 5 min measurements in the treatment eye only. p values <= 0.05
      were considered statistically significant. Mist application to treatment eye
      produced an increase in 1 min and 5 min PSV and EDV (0.001 < p < 0.03) and a
      decrease in 5 min RI (p = 0.01), with no significant changes in PSV, EDV or RI of
      control eye or in treatment eye 1 min RI (p > 0.05). Drop application to
      treatment eye produced an increase in PSV (p < 0.001) and EDV (p = 0.01) at 1
      min, with an increase in control eye 1 min PSV and EDV (p = 0.03). There were no
      statistically significant changes in treatment eye PSV, EDV and RI after 5 min (p
      > 0.05). The use of nebulized mist may provide an effective alternative to liquid
      drop medication application. 

PMID- 24300299
TI  - Levofloxacin-proliposomes: opportunities for use in lung tuberculosis.
AB  - Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that
      has good activity against Mycobacterium tuberculosis. The aims of this study were
      to develop and evaluate LEV-proliposomes in a dry powder aerosol form for
      pulmonary delivery. LEV-proliposomes containing LEV, soybean phosphatidylcholine,
      cholesterol and porous mannitol were prepared by a spray drying technique. The
      physicochemical properties of LEV-proliposomes were determined using a cascade
      impactor, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and
      Fourier transform infrared spectroscopy (FT-IR). The toxicity of proliposomes to
      respiratory-associated cell lines and its potential to provoke immunological
      responses from alveolar macrophages (AMs) were evaluated. Antimycobacterial
      activity using flow cytometry and an in vivo repeated dose toxicity test in rats
      were carried out. LEV-proliposomes were successfully prepared with mass median
      aerodynamic diameters of 4.15-4.44 MUm and with fine particle fractions
      (aerosolized particles of less than 4.4 um) of 13%-38% at 60 L/min. LEV
      proliposomes were less toxic to respiratory-associated cells than LEV, and did
      not activate AMs to produce inflammatory mediators that included interleukin
      1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide. The
      minimum inhibitory concentration (MIC) against M. bovis of LEV and LEV
      proliposomes containing LEV 10% were 1 and 0.5 ug/mL, respectively. The efficacy
      of LEV-proliposomes against M. bovis was significantly higher than that of free
      LEV (p < 0.05). The efficacy of the LEV-proliposomes against M. tuberculosis was
      equal to that of the free LEV (MIC = 0.195 ug/mL). In a repeated dose toxicity
      study in rats, renal and liver toxicity was not observed. LEV-proliposomes should
      now be tested as an alternative formulation for delivering LEV to the lower
      airways. 

PMID- 24300300
TI  - Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through
      Porcine Membrane from Aqueous Saturated Solutions.
AB  - The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine
      (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA),
      pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2
      hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts
      were re-crystallized from water in order to obtain forms that are stable in the
      presence of water. Vertical Franz-type cells with a diffusional surface area of
      9.62 cm2 were used to study the permeation of these diclofenac salts from their
      saturated solutions through an internal pig ear membrane. The receptor
      compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a
      saturated solution (5 mL) of each salt was placed in the donor compartment,
      thermostated at 37  degrees C. Aliquots were withdrawn at predetermined time
      intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined
      by plotting the permeated amount, normalized for the membrane surface area versus
      time. Permeation coefficients were obtained dividing the flux values J by the
      concentration of the releasing phase-that is, water solubility of each salt.
      Experimental results show that fluxes could be measured when diclofenac salts
      with aliphatic amines are released from a saturated aqueous solution. Different
      chemical species (acid, anion, ion pairs) contribute to permeation of the anti
      inflammatory agent even though ion-pairs could be hypothesized to operate to a
      greater extent. Permeation coefficients were found higher when the counterion
      contains a ring; while hydroxy groups alone do not appear to play an important
      role, the ring could sustain permeation, disrupting the organized domains of the
      membrane. 

PMID- 24300301
TI  - Influence of the efavirenz micronization on tableting and dissolution.
AB  - The purpose of this study was to propose an analytical procedure that provides
      the effects of particle size and surface area on dissolution of efavirenz. Five
      different batches obtained by different micronization processes and with
      different particle size distribution and surface area were studied. The
      preformulation studies and dissolution curves were used to confirm the particle
      size distribution effect on drug solubility. No polymorphic variety or
      amorphization was observed in the tested batches and the particle size
      distribution was determined as directly responsible for the improvement of drug
      dissolution. The influence of the preparation process on the tablets derived from
      efavirenz was observed in the final dissolution result in which agglomeration,
      usually seen in non-lipophilic micronized material, was avoided through the use
      of an appropriate wet granulation method. For these reasons, micronization may
      represent one viable alternative for the formulation of brick dust drugs. 

PMID- 24300302
TI  - Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose
      Co-Administered with DPP-4 Inhibitors in Japan.
AB  - After the launch of dipeptidyl peptidase-4 (DPP-4), a new oral hypoglycemic drug
      (OHD), in December 2009, severe hypoglycemia cases were reported in Japan.
      Although the definite cause was unknown, co-administration with sulfonylureas
      (SU) was suspected as one of the potential risk factors. The Japan Association
      for Diabetes Education and Care (JADEC) released a recommendation in April 2010
      to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide)
      when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk
      minimization action along with labeling changes, dispensing records for 114,263
      patients prescribed OHDs between December 2008 and December 2010 were identified
      in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended
      dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to
      63.8% after the JADEC recommendation (p < 0.01 by time-series analysis), while no
      change was found in those for SU monotherapy and SU with other OHD co
      prescriptions. The adherence was significantly worse for those receiving a
      glibenclamide prescription. The JADEC recommendation, along with labeling
      changes, appeared to have a favorable effect on the risk minimization action in
      Japan. In these instances, a pharmacy claims database can be a useful tool to
      evaluate risk minimization actions. 

PMID- 24300304
TI  - The tolerance of the Arabidopsis defense hormone receptor mutant coi1 against the
      vascular pathogen Verticillium longisporum is not due to increased levels of the
      active hormone jasmonoyl-isoleucine.
AB  - Verticillium longisporum is a soil-borne vascular pathogen found primarily on
      oilseed rape in Northern Europe. Infection of the model plant Arabidopsis
      thaliana can be achieved under laboratory conditions. In the article related to
      this addendum, we have shown that Arabidopsis dde2-2 mutants that are compromised
      in their ability to synthesize the defense hormone jasmonoyl-isoleucine (JA-Ile)
      are slightly more susceptible than wild-type. Contrary to the expectation that
      hormone biosynthesis mutants and their respective receptor mutants should have
      the same phenotype, we found that plants that lack the JA-Ile receptor CORONATINE
      INSENSITIVE1 (COI1) are more tolerant to the disease. This addendum addressed the
      question whether the increased JA-Ile levels found in coi1 are responsible for
      its tolerance phenotype. Based on the evidence that the JA-Ile-deficient dde2-2
      coi1-t double mutant is as tolerant as coi1-t, we conclude that increased JA-Ile
      levels do not protect Arabidopsis against the fungus in the absence of COI1. 

PMID- 24300303
TI  - Pore positioning: current concepts in Pannexin channel trafficking.
AB  - Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that
      play key roles in a number of physiological and pathophysiological settings.
      These single membrane large-pore channels exhibit a variety of tissue, cell type,
      and subcellular distributions. The lifecycles of Panxs are complex, yet must be
      understood to accurately target these proteins for future therapeutic use. Here
      we review the basics of Panx function and localization, and then analyze the
      recent advances in knowledge regarding Panx trafficking. We examine several
      intrinsic features of Panxs including specific post-translational modifications,
      the divergent C-termini, and oligomerization, all of which contribute to Panx
      anterograde transport pathways. Further, we examine the potential influence of
      extrinsic factors, such as protein-protein interactions, on Panx trafficking.
      Finally, we highlight what is currently known with respect to Panx
      internalization and retrograde transport, and present new data illustrating Panx1
      internalization following an activating stimulus. 

PMID- 24300305
TI  - Coeliac disease screening in first-degree relatives on the basis of biopsy and
      genetic risk.
AB  - BACKGROUND: Serological markers of coeliac disease (CD) lack diagnostic value to
      identify mild histopathological lesions mainly in adults at risk of CD. AIMS: The
      aim of this study was to evaluate the usefulness of human leukocyte antigen (HLA)
      DQ2/8 genotyping, followed by duodenal biopsy for the detection of CD in adult
      first-degree relatives (FDRs) of patients with CD. MATERIALS AND METHODS: Ninety
      two adult DQ2/8 positive FDRs were consecutively included. A duodenal biopsy was
      offered irrespective of the serology result or associated symptoms. The clinical
      features, associated autoimmune diseases and biochemical parameters were
      recorded. RESULTS: Sixty-seven FDRs (mean age 34 years) underwent a duodenal
      biopsy. Histopathological alterations were found in 32 (48%) and showed the
      following stages: 12 Marsh I (18%), one Marsh II (1.5%), four Marsh IIIA (6%),
      five Marsh IIIB (7.5%) and 10 Marsh IIIC (15%). Positive serological markers were
      present in 17/67 (25%), with only one showing Marsh I and the remainder
      presenting some degree of duodenal atrophy (Marsh III). In addition, 33/67 (54%)
      had gastrointestinal symptoms, with dyspepsia being the most prevalent. The
      distribution of symptoms, anaemia and autoimmune disease was independent of the
      duodenal histopathological stage. Serology-based screening would diagnose 50% of
      the cases showing any degree of CD spectrum and miss 6% of the cases with mucosal
      atrophy. CONCLUSION: Adult FDRs of patients with CD can benefit from a screening
      strategy on the basis of HLA-DQ genotyping, followed by a duodenal biopsy.
      Gastrointestinal symptoms and lymphocytic enteritis are common findings that may
      benefit from a gluten-free diet.

PMID- 24300306
TI  - Setting limits on supersymmetry using simplified models.
AB  - Experimental limits on supersymmetry and similar theories are difficult to set
      because of the enormous available parameter space and difficult to generalize
      because of the complexity of single points. Therefore, more phenomenological,
      simplified models are becoming popular for setting experimental limits, as they
      have clearer physical interpretations. The use of these simplified model limits
      to set a real limit on a concrete theory has not, however, been demonstrated.
      This paper recasts simplified model limits into limits on a specific and complete
      supersymmetry model, minimal supergravity. Limits obtained under various physical
      assumptions are comparable to those produced by directed searches. A prescription
      is provided for calculating conservative and aggressive limits on additional
      theories. Using acceptance and efficiency tables along with the expected and
      observed numbers of events in various signal regions, LHC experimental results
      can be recast in this manner into almost any theoretical framework, including
      nonsupersymmetric theories with supersymmetry-like signatures. 

PMID- 24300307
TI  - Cost-effectiveness analysis at 2 years of surgical treatment of benign prostatic
      hyperplasia by photoselective vaporization of the prostate with GreenLight-Photo
      vaporization 120 W versus transurethral resection of the prostate.
AB  - INTRODUCTION: Transurethral resection of the prostate is the gold standard of
      surgical treatment of lower urinary tract symptoms associated to benign prostate
      hyperplasia. The new Green Light Photovaporization has been shown to be an
      alternative that is as effective for this condition as the transurethral
      resection of the prostate. OBJECTIVES: To compare the efficiency of Green Light
      Photovaporization 120 W versus transurethral resection of the prostate in the
      treatment of benign prostate hyperplasia (BPH) in a 2-year time horizon from the
      perspective of the Spanish health service perspective. METHODS: A cost utility
      analysis was performed retrospectively with the data from 98 patients treated
      sequentially with transurethral resection of the prostate (n: 50) and Green Light
      Photovaporization 120 W (n: 48). A Markov model was designed to estimate the cost
      (2012?) and results (quality adjusted life years) in a 2-year time horizon.
      RESULTS: The total cost associated to Green Light Photovaporization 120 W
      treatment was less (3,377?; 95% CI: 3,228; 3,537) than that of the transurethral
      resection of the prostate (3,770?; 95% CI: 3,579; 3,945). The determining factor
      of the cost was the surgical phase (difference: -450?; 95% CI: -625; -158)
      because admission to hospital after surgery was not necessary with the GreenLight
      PhotoVaporization. CONCLUSIONS: Surgical treatment of BPH patients with
      GreenLight-PhotoVaporization 120 W is more efficient than transurethral resection
      of the prostate in the surgical treatment of benign prostate hyperplasia as it
      has similar effectiveness and lower cost (-393?; 95% CI: -625; -158).

PMID- 24300308
TI  - The influence of pretarget distracter stream properties on the skeletal
      attentional blink.
AB  - The attentional blink (AB) occurs when the limits of temporal processing are
      reached. In a typical AB experiment, two targets (T1, T2) are presented within a
      stream of distracters, and detection of T2 is impaired when presented shortly
      after T1. Several theories focus on the mechanism underlying this deficit, among
      them proposals that see the similarity between distracters and targets as a
      crucial factor. The present study aimed to gain a better understanding of the
      effect of distracter stream properties on performance in the AB paradigm. A
      skeletal AB task was combined with a pretarget distracter stream. The presence
      and familiarity of the distracter stream and its similarityto the targets were
      manipulated in three separate experiments. The last distracter before T1 was
      sufficient to impair T1 detection in the standard rapid serial visual
      presentation (RSVP) paradigm. Second, T2|T1 performance was impaired by an RSVP
      stream with low target-distracter similarity but unfamiliar stimuli. Finally, a
      single mask before T1 was shown to impair T2|T1. The results suggest that it is
      the last distracter before T1, rather than the RSVP stream per se, that impairs
      T1 detection performance. T2|T1 performance is influenced by a combination of
      transient attentional capture mechanisms that include but are not limited to
      target-distracter similarity. Thus, the size of an AB is determined not only by
      target-distracter similarity but by the overall processing demands of the
      distracters.

PMID- 24300309
TI  - Sibilant /s/ simulator based on computed tomography images and dental casts.
AB  - The sibilant /s/ is produced by raising the tongue against the roof of the mouth
      to form a narrow constriction, which is adjusted so that the airstream emerging
      from it impinges on the incisors. However, the location where the sibilant sound
      occurs is unclear, as are the details of the mechanisms of its generation. In
      this study, we used a realistically shaped replica produced with a three
      dimensional printer and demonstrated that turbulent flow was generated in the
      oral tract near the incisors and lips and that sufficiently developed turbulent
      flow generated a sound source up to 20,000 Hz at 333, 500, and 667 cm(3)/sec,
      which agrees with the range of physiological flow rates typical for /s/. The
      characteristics of the sound spectra agreed with those of the sibilant /s/ sound
      emitted by our control individual. Such a physical perspective could yield
      knowledge useful for oral surgery and speech science - for example, to predict
      how the generation of sibilants may be occasionally affected by orthodontic and
      prosthodontic treatments.

PMID- 24300310
TI  - Novel mutations in PTH1R associated with primary failure of eruption and
      osteoarthritis.
AB  - Autosomal dominant mutations in PTH1R segregate with primary failure of eruption
      (PFE), marked by clinical eruption failure of adult teeth without mechanical
      obstruction. While the diagnosis of PFE conveys a poor dental prognosis, there
      are no reports of PFE patients who carry PTH1R mutations and exhibit any other
      skeletal problems. We performed polymerase chain reaction-based mutational
      analysis of the PTH1R gene to determine the genetic contribution of PTH1R in 10
      families with PFE. Sequence analysis of the coding regions and intron-exon
      boundaries of the PTH1R gene in 10 families (n = 54) and 7 isolated individuals
      revealed 2 novel autosomal dominant mutations in PTH1R (c.996_997insC and
      C.572delA) that occur in the coding region and result in a truncated protein. One
      family showed incomplete penetrance. Of 10 families diagnosed with PFE, 8 did not
      reveal functional (nonsynonymous) mutations in PTH1R; furthermore, 4 families and
      1 sporadic case carried synonymous single-nucleotide polymorphisms. Five PFE
      patients in 2 families carried PTH1R mutations and presented with osteoarthritis.
      We propose that the autosomal dominant mutations of PTH1R that cause PFE may also
      be associated with osteoarthritis; a dose-dependent model may explain isolated
      PFE and osteoarthritis in the absence of other known symptoms in the skeletal
      system.

PMID- 24300311
TI  - Novel fluoro-carbon functional monomer for dental bonding.
AB  - Among several functional monomers, 10-methacryloxydecyl dihydrogen phosphate (10
      MDP) bonded most effectively to hydroxyapatite (HAp). However, more hydrolysis
      resistant functional monomers are needed to improve bond durability. Here, we
      investigated the adhesive potential of the novel fluoro-carbon functional monomer
      6-methacryloxy-2,2,3,3,4,4,5,5-octafluorohexyl dihydrogen phosphate (MF8P;
      Kuraray Noritake Dental Inc., Tokyo, Japan) by studying its molecular interaction
      with powder HAp using solid-state nuclear magnetic resonance ((1)H MAS NMR) and
      with dentin using x-ray diffraction (XRD) and by characterizing its interface
      ultrastructure at dentin using transmission electron microscopy (TEM). We further
      determined the dissolution rate of the MF8P_Ca salt, the hydrophobicity of MF8P,
      and the bond strength of an experimental MF8P-based adhesive to dentin. NMR
      confirmed chemical adsorption of MF8P onto HAp. XRD and TEM revealed MF8P_Ca salt
      formation and nano-layering at dentin. The MF8P_Ca salt was as stable as that of
      10-MDP; MF8P was as hydrophobic as 10-MDP; a significantly higher bond strength
      was recorded for MF8P than for 10-MDP. In conclusion, MF8P chemically bonded to
      HAp. Despite its shorter size, MF8P possesses characteristics similar to those of
      10-MDP, most likely to be associated with the strong chemical bond between
      fluorine and carbon. Since favorable bond strength to dentin was recorded, MF8P
      can be considered a good candidate functional monomer for bonding.

PMID- 24300313
TI  - [Prevalence of major depression in the arthritic conditions of Canadian
      populations: a comparative study between English-speaking majority and
      francophones in minority communities].
AB  - OBJECTIVE: Mental health and arthritis have been recognized as major public
      health issues. Francophone minority status has now been acknowledged as a health
      determinant. The objective of this study was to determine the prevalence of major
      depression among adults with arthritis in Francophone minority populations
      compared to the Anglophone majority. METHODS: Secondary analysis of the CCHS
      (merger of 2003 (cycle 2.1), 2005 (Cycle 3.1), 2007 (cycle 4.1), 2008 and 2009)
      excluding Quebec residents. The language variable was constructed using an
      existing algorithm which combines maternal tongue, language of conversation,
      language of interview, and preferred language. Major depression was defined
      according to the DSM IV. Presence or absence of arthritis was a self-reported
      variable. The prevalence and odds ratios for depression in people with arthritis
      were calculated and adjusted for various factors (socio-economic, social
      isolation, access to health services). RESULTS: The study identified 159,426
      Anglophones and 10,658 Francophones. Among the participants with arthritis (27%),
      the prevalence of depression in Francophones and Anglophones was 8.5% and 8.4%,
      respectively. In men, Anglophones were more at risk for depression than
      Francophones: OR 2.36 (95% CI: 2.07-2.70) vs. OR 1.87 (95% CI: 1.20-2.91). This
      trend was not observed in women. CONCLUSION: In our sample of people with
      arthritis, depression seems to affect more particularly the English-speaking men,
      however given the small sample size, we need to be cautious in our conclusions.

PMID- 24300314
TI  - [Access to the early diagnosis of dementia in New Brunswick: perceptions of
      potential users of services depending on the language and the middle of life].
AB  - OBJECTIVES: The early diagnosis of dementia (EDD) enables the identification of
      reversible causes of dementia and allows the timely implementation of secondary
      preventive and therapeutic interventions. This study explores New Brunswick
      seniors' perceptions of the accessibility and availability of EDD services as
      well as their satisfaction with them while taking into account their language of
      use and place of residence (urban or rural). METHOD: Self-administered survey
      exploring perceptions of EDD services in Francophone and Anglophone seniors from
      rural and urban areas of New Brunswick. Univariate and bivariate analyses were
      carried out. RESULTS: Of the 157 participants aged 65 years and over who filled
      out the survey and whose data were analyzed, 84 identified as Francophone, 72 of
      whom lived in rural areas. Bivariate analyses showed that linguistic groups were
      comparable with regard to their perceptions of the availability, access to, and
      satisfaction with EDD services. However, when taking the geographic dimension
      into account, linguistic intergroup and intragroup disparities were observed,
      notably in the areas pertaining to the type of services available in the area.
      CONCLUSIONS: These results suggest that seniors who live in rural areas of New
      Brunswick are a particularly vulnerable group with perceived limited access to
      EDD services in their area.

PMID- 24300315
TI  - [The surplus weight among the Francophones and Anglophones].
AB  - OBJECTIVES: Recent studies show a higher prevalence of being obese or overweight
      in Francophones living in minority settings compared to Canada's Anglophone
      majority. The objective of our study was to determine whether belonging to the
      linguistic minority constituted a social determinant of having a weight problem.
      METHODS: Descriptive variables (n=128,986) from five cycles of the Canadian
      Community Health Survey were stratified by respondents' language and sex. Two
      logistic regression models tested the association between being overweight/obese
      (as defined by the measure of body mass index) and language, for men and women,
      while adjusting for social and behavioural determinants. RESULTS: Prevalence of
      excess weight was higher among Francophones compared to Anglophones of Ontario,
      although the difference was not significant after adjustment for socio-economic
      and behavioural determinants. However, Francophones were older, less educated and
      more likely to live in rural areas than their Anglophone counterparts, a
      situation which makes them more vulnerable. CONCLUSION: The study confirms the
      role of social and behavioural determinants of being obese/overweight. Although
      language does not have a direct influence on having a weight problem, the socio
      economic reality of the Francophone minority makes them more likely than the
      Anglophone majority to fall in vulnerable strata of the population with regards
      to being overweight/obese. This situation should be considered when planning
      health services.

PMID- 24300316
TI  - Physical inactivity among Francophones and Anglophones in Canada.
AB  - OBJECTIVE: Leisure-time physical activity participation is influenced by various
      socio-demographic factors. Recent evidence suggests that being part of a minority
      negatively impacts an individual's health status. The objective of this study was
      to compare inactive leisure-time physical activity between the Francophone
      minority and the Anglophone majority in Canada. METHODS: Data from the fusion of
      cycles 2.1, 3.1, 4.1, 2008 and 2009 of the Canadian Community Health Survey
      (CCHS) were used. The linguistic variable was determined by languages spoken at
      home, first language learned and still understood, language of interview, and
      language of preference. Leisure-time physical activity was based on a
      questionnaire provided during the interview. Factors associated with inactive
      leisure time were examined using logistic regression models. RESULTS:
      Francophones were more likely than Anglophones to be physically inactive in their
      leisure time (49.1% vs. 47.2%). A greater percentage of Francophones had poor
      self-perceived health, were older, were single, had lower education, had higher
      rate of unemployment and lived in rural areas compared to Anglophones. When these
      socio-demographic factors were taken into account, there were no further
      differences in the likelihood of being inactive between Francophones and
      Anglophones. CONCLUSION: The Francophone minority in Canada is characterized by
      socio-demographic factors that have a negative impact on leisure-time physical
      activity participation.

PMID- 24300317
TI  - Editorial.

PMID- 24300318
TI  - Comparison of dietary intake between Francophones and Anglophones in Canada: data
      from CCHS 2.2.
AB  - OBJECTIVE: To compare the dietary intake and food choices between Francophone
      Canadians in a state of linguistic minority (outside of Quebec) and the English
      speaking majority. METHODS: We used the 2004 Canadian Community Health Survey
      (CCHS) cycle 2.2 (general health and 24-hour dietary recalls) to describe dietary
      intake of Francophone Canadians (excluding Quebec) and compare them to the
      English-speaking majority. The linguistic variable was determined by languages
      spoken at home, first language learned and still understood, language of
      interview, and language of preference. The mean differences in daily nutrient and
      food intake were assessed by t and chi-square tests. RESULTS: Differences in
      total energy and daily food intakes by language groups were not observed in the
      sample; however, significant differences in weekly consumption were found in
      different age and sex categories: lower fruits and vegetables consumption, and
      vitamins and macronutrients intakes for older Francophone men and higher intakes
      of energy and saturated fat from "unhealthy" foods for Francophone men 19-30
      years of age. Based on the Acceptable Macronutrients Distribution Range (AMDR),
      approximately 50% of the sample exceeded their acceptable energy intake from
      saturated fats, and 80% were below their required intake of linoleic fatty acid.
      CONCLUSION: We confirmed that belonging to Francophone minorities in Canada
      affects food choices and nutritional well-being of this population. The most
      vulnerable groups identified by our study were Francophone men in the youngest
      (19-30) and older (50 and over) age categories. The extent to which the cultural
      setting influences the diet and, in turn, the health of the minority population
      needs further examination.

PMID- 24300319
TI  - [Nutritional screening among seniors in health care institutions: comparison
      between the institutions Francophones and Anglophones].
AB  - OBJECTIVES: Malnutrition among the elderly is a widespread problem in hospitals
      and nursing homes. However, data on the practice of nutritional screening in
      these facilities are limited, particularly in Francophone establishments. This
      study aimed to compare nutritional screening practices among the elderly in
      Anglophone and Francophone health care facilities in New Brunswick (NB), as well
      as perceptions and practices of health care professionals. METHODS: Information
      on screening parameters was taken directly from elderly patients'/residents'
      medical records. Health care professionals' (doctors, nurses, dietitians)
      perceptions and practices of nutritional screening were collected through
      questionnaires. RESULTS: A total of five hospitals and 31 nursing homes in NB
      took part in the study. Of these, 421 patients/residents and 457 health
      professionals participated. Significant differences in the availability of
      screening parameters were observed between Francophone and Anglophone
      patients/residents. Certain screening parameters, such as weight at admission,
      loss of appetite and meal fractions consumed were less available in Francophone
      patients'/residents' records. In addition, health care professionals' perceptions
      regarding nutritional screening varied by occupation and language of the
      establishment. Several barriers to screening were also identified. CONCLUSION:
      Reduced availability of screening parameters in Francophone establishments and
      the underestimation of malnutrition in elderly patients/residents by doctors and
      nurses are barriers that can influence nutritional screening in Francophone
      health care facilities.

PMID- 24300320
TI  - Recruiting doctors from and for underserved groups: Does New Brunswick's
      initiative to recruit doctors for its linguistic minority help rural communities?
AB  - OBJECTIVES: Within health care, there are underserved groups. New Brunswick's
      French-speaking minority, which also mostly lives in rural communities, is one
      such group. A physician shortage potentially prevents this population from
      accessing health promotion and clinical prevention services. This study analyzes
      whether New Brunswick Francophone doctors with rural backgrounds are more likely
      than doctors from urban regions to set up practice in rural communities of the
      province. METHODS: A questionnaire was sent to 390 New Brunswick Francophone
      physicians admitted in medicine between 1973 and 2000. It collected information
      on geographic origin and history of medical practice. Multivariate logistic
      regressions were used to identify whether a rural background is associated with
      the likelihood of ever and currently practicing in rural communities. We used the
      General Practice Rurality Index-simplified to quantify the rurality level of
      communities. RESULTS: In total, 264 (67%) physicians participated. A rural
      background was positively associated with the establishment of a first medical
      practice in a rural community. This relationship was only significant among
      family physicians. There was no statistically significant relationship between
      rurality of community of origin and rurality of current community of practice
      among either family or specialty physicians. CONCLUSION: Although Francophone
      doctors with a rural background were more likely than their urban counterparts to
      set up their first practice in a rural community, this effect was not sustained.
      This raises questions as to why they leave rural communities and highlights the
      importance of measures to retain doctors as a way to promote public health for
      underserved rural groups.

PMID- 24300321
TI  - [Validation of the equity of access of the OLMCS to health professionals in
      health regions of Canada].
AB  - OBJECTIVE: Our research uses a regional summary indicator (IHPOLM) to measure the
      capacity of the health system to provide equitable access to health professionals
      for 2 million Official Language Minority Community (OLMC) members dispersed
      across 104 health regions in Canada. METHOD: The summary indicator IHPOLM
      compares the official language minority and the official language majority
      potential access to health professionals. The IHPOLM indicator uses 22
      professional health care occupations, representing 79% of the health care
      workforce in Canada, who communicate directly with their clientele for
      therapeutic or diagnostic purposes (Statistics Canada, 2006). RESULTS: The IHPOLM
      indicator revealed that the OLMC population is at a disadvantage in potential
      access to health professionals capable of providing services in the minority
      language when compared to the majority language population in 10 of the 13
      Canadian provinces/territories. OLMC members are disadvantaged in 13 out of 14
      health regions in Ontario, in 16 out of 18 in Quebec and in 3 out of 7 in New
      Brunswick. CONCLUSION: The summary regional indicator IHPOLM identified OLMC
      health care access inequalities between the official language minority population
      and the majority language population in the health care system across the health
      regions in Canada. The more detailed analysis of IHPOLM for individual health
      occupations will further improve our knowledge of Official Language Minority
      Community health access inequalities.

PMID- 24300322
TI  - Official language minority communities in Canada: is linguistic minority status a
      determinant of mental health?
AB  - OBJECTIVES: Language has been identified as a determinant of mental health.
      Within Canada, individuals may speak an official language and still belong within
      the linguistic minority (Francophones outside Quebec and Anglophones within
      Quebec). The objectives of this study were to compare mental health problems
      between minority and majority official language communities, and examine the
      association between official language minority and mental health problems.
      METHODS: Data from the Canadian Community Health Survey, Cycle 1.2 were used to
      make two comparisons: Francophones to Anglophones within Quebec, and Francophones
      to Anglophones outside Quebec. Twelve-month and lifetime prevalences of mental
      disorders (major depressive episode, anxiety disorders, and alcohol/substance
      abuse/dependence) and mental health indices were compared. Logistic regression
      analysis examined whether official language minority status was a determinant of
      mental health. RESULTS: Mental health between minority and majority language
      groups was similar. Official language minority status was not a significant
      determinant of mental health. Self-rated mental health indices varied between
      groups. In some cases, minority language groups reported lower levels of life
      satisfaction (minority Anglophones versus majority Francophones), while in other
      cases more majority Anglophones reported poor life satisfaction and mental health
      (majority Anglophones versus minority Francophones). CONCLUSIONS: Overall, few
      differences were found between language groups, though variations in self-rated
      mental health indices were observed. In order to better understand the role of
      context in determining health outcomes, future research should examine mental
      health problems among official language minority groups provincially to help
      stakeholders in directing resources and programs to populations in most need.

PMID- 24300323
TI  - Methodological issues in analyzing small populations using CCHS cycles based on
      the official language minority studies.
AB  - Statistical analyses for small populations or small domains of interest can be
      challenging. To obtain reliable estimates, only very large surveys such as the
      Canadian Community Health Survey can be considered. However, despite its good
      geographical and temporal coverage, the analysis of small populations in smaller
      regions (e.g., health regions) and in regards to specific health issues remains
      challenging. We will look at the methodological issues in analysis of small
      populations in relation to sampling and non-sampling survey errors that affect
      the precision and accuracy of the estimates. Francophone minorities in Canada
      will be used to illustrate the issues throughout the paper.

PMID- 24300324
TI  - [The concept mapping of representations of the future of health services in
      French in linguistic minority].
AB  - OBJECTIVE: In the context of institutional incompleteness affecting the official
      minority language communities, we examine how the Francophones in a minority
      context see the future of health services offered in French. METHOD: The study is
      based on a participatory methodology: the concept mapping will serve to identify
      the conceptual universe of a given problem. From a master statement such as:
      "When I think about the future of health services in French, I think of ...",
      participants are invited to make as many statements as come to mind. These
      statements are then categorized individually and treated collectively through a
      multivariate analysis. OUTCOME: The main themes emerging from the mapping
      exercise indicate the issues and challenges raised by the participants, namely
      the geographical context, specific needs, language rights, education and
      training, human resources, bilingualism and translation, the minority experience,
      active offer, the role of governmental bodies, community mobilization,
      collaboration and networking. CONCLUSION: The participatory approach that concept
      mapping allows is interesting in more than one way: its flexibility provides a
      space for both individual and collective reflection; it allows identification and
      structuring of the crucial dimensions of an issue; and the research outcomes are
      useful both to researchers and participants in guiding action and achieving
      goals. Social actors can therefore benefit from a collective dynamic to reflect
      on the foundations for the development and organization of health services in
      French.

PMID- 24300325
TI  - [Perception of the linguistic and cultural context minority on the lived
      experiences of pregnancy].
AB  - OBJECTIVE: From a public health perspective, the follow-up of women during
      pregnancy and the perinatal period requires quality communication and health
      services that take into account the context in which these women live. However,
      challenges related to access to health services in French in a minority situation
      have been documented in recent research. The objective of this pilot study is to
      better understand the perceptions, the lived experiences and the needs of
      pregnant Francophone women living in Canada within a linguistic minority context.
      METHODS: Given the exploratory nature of the inquiry, a mixed method descriptive
      study was conducted in Alberta and New Brunswick, whose populations are 2% and
      33% Francophone, respectively. Two semi-structured interviews and a series of
      validated questionnaires were administered to 21 pregnant women during the third
      trimester of pregnancy and at six weeks postnatal. Based on the questionnaires, a
      descriptive analysis documented participants' characteristics, and qualitative
      interviews were transcribed, coded and analyzed through an inductive process by
      four independent readers to uncover key themes related to the participants'
      experiences. RESULTS: Most of the women were bilingual and language in which
      health services were received did not appear to be a major issue for them, except
      during times of stress and at critical periods of the pregnancy. In contrast,
      almost one third of the women reported being unsatisfied with services they had
      received and attributed this dissatisfaction to gaps in French language services.
      CONCLUSION: Women prefer to receive health services in their mother tongue,
      however services are delivered in English most of the time. Participants report
      that during times of stress and emergency, communication in French is essential
      to a quality follow-up of patients. Linguistic and cultural congruence seems to
      be a key factor for quality care during pregnancy. A comparative study would
      assist in better ascertaining the relative impact of language on Francophone
      women's lived experiences during pregnancy.

PMID- 24300326
TI  - [The perception of seniors Francophones in a minority situation coping with the
      challenges and issues related to the maintenance at home in urban areas New
      Brunswickers].
AB  - OBJECTIVE: Explore the needs and the degree of satisfaction of Francophone
      seniors living in a minority socio-linguistic urban community in regards to aging
      in-place. METHOD: An ethnographic case study was conducted in an urban community
      in the province of New Brunswick between October 2010 and June 2011. Individual
      interviews were completed with leaders of different community organizations (n=9)
      and focus groups were held with socio-linguistic minority French-speaking older
      adults (n=19). RESULTS: Francophone seniors explained their willingness to age-in
      place; however, the lack of services and support in the community makes aging-in
      place difficult. Despite this identified absence of services, leaders of various
      community organizations have no plans to review current services in order to
      facilitate better quality of life for seniors. CONCLUSION: Aging-in-place for
      French-speaking seniors living in socio-linguistic minority communities requires
      concerted efforts from family members, the community and the government. The
      Ottawa Charter of Health clearly states housing as a prerequisite of health.
      Housing and social support are important determinants of health. Therefore, the
      development and implementation of a public policy with regard to seniors, and
      particularly those in a socio-linguistic minority, seems fundamental in the
      context of population aging.

PMID- 24300327
TI  - [Inequities in health in minority communities: diagnosis of the situation among
      the Francophone immigrants of Sudbury].
AB  - OBJECTIVES: This article aims to uncover health inequities related not only to
      living in a linguistic minority, but also to being an immigrant and living in a
      new environment with a cultural background different from that of the host
      community. METHODS: This qualitative study presents the personal experiences of
      many Francophone immigrants in relation to services and health care in Sudbury
      and their perception about the quality and accessibility of these services and
      health care. Seventy-two (72) respondents aged between 18 and 65 years (45 men
      and 27 women) participated in this research through individual interviews and
      focus groups. RESULTS: The results show, among other things, that being immigrant
      and Francophone limits access to health services, affects the quality of these
      services and hinders being well supported when encountering health problems. Thus
      some individuals are not even able to give informed consent when making important
      decisions about their own health. CONCLUSION: The article makes recommendations
      that would allow access to better services and health care for immigrants, and
      would contribute to improving the health of the Canadian population of which they
      are an integral part.

PMID- 24300328
TI  - [The vulnerability of women Francophone parent at risk of homelessness in a
      community in Northern Ontario].
AB  - OBJECTIVE: This study aimed to examine the vulnerability of Francophone single
      mothers at risk of homelessness in Northern Ontario. The project also endeavoured
      to document the quest for autonomy of these women in a minority context. METHOD:
      Employing a qualitative approach, eleven life stories were obtained from five
      women. Although none were homeless at the time of the interviews, in terms of
      living on the street, two were living with friends and the others were at risk of
      becoming homeless. All of the participants were between 20 and 59 years old and
      had completed their secondary education. RESULTS: Taking into account their
      economic and social situation, as well as the participants' health and cultural
      resources, vulnerabilities throughout the life course were analyzed. CONCLUSION:
      The life trajectory of these women showed us that their significant
      vulnerabilities are relative to the amount of autonomy they are able to secure
      through the services provided by supporting agencies, particularly in a
      linguistic minority context. In addition, the triple stigmatization (economic,
      linguistic and gender relations) requires a broader understanding of the
      resilience of these women in their journey from poverty (economic) to social (and
      linguistic) exclusion, and vulnerability. Despite these challenges, each of the
      individuals interviewed in this study, for whom the quest for autonomy is a
      continual struggle, demonstrated resilience.

PMID- 24300329
TI  - [The priorities for research on the health of Francophones in Ontario].
AB  - OBJECTIVES: Several studies have demonstrated the health inequity between
      Francophones in minority-language communities (FMLC) and their English
      counterparts. While Ontario has the largest number of FMLC in Canada, health
      research priorities for FMLC have not yet been determined in this province. This
      article aims to fill this gap. METHODS: An online 2-round Delphi consultation was
      conducted electronically with Francophone researchers, policy-makers, community
      members and health professionals working or living in Ontario. Themes and
      subthemes were identified based on the literature. In order to assess the
      differences in opinion between participants, a Kruskal-Wallis test was performed
      in the second round. RESULTS: There were 34 participants in the first round and
      31 in the second round. The top three priorities that emerged were: health
      services in French, health human resources, and health services policy in French.
      Among the subthemes listed within these three priorities, education in French and
      planning services were ranked among the top three priorities in the four groups.
      CONCLUSION: The participatory approach used in this study relied on the opinion
      of all stakeholders. The results obtained can inform future research agenda and
      inform the development of health policies for the provision of health services in
      French with a higher probability of responding adequately to the needs of
      Francophone users.

PMID- 24300330
TI  - Implementing the evidence for language-appropriate health care systems: The Welsh
      context.
AB  - Like Canada, Wales, UK is a bilingual nation: the Welsh language is an important
      part of its national identity and legislative framework. This has implications
      for the delivery of public sector services, particularly in the context of health
      and social care, where responding to the language needs of service users is
      fundamental to quality health care provision. Nevertheless, despite the
      strengthening policy commitment for a whole-system approach towards enhancing
      Welsh language services, there is a paucity of evidence to guide best practice in
      organizational planning in health care settings. This commentary outlines the
      context and significance of bilingual health care provision in Wales and the
      implications for building and embedding the evidence base. It calls for further
      work to translate our knowledge and understanding of language-appropriate
      practice to provide more effective and sensitive health care services; and to
      close the implementation gap between evidence and practice. Given the relevance
      of this challenge for health care providers in Canada who plan and deliver
      services for French-language minorities, this approach has resonance across our
      research communities. Thus, in our common pursuit to establish integrated
      knowledge translation research for language-appropriate health care systems, this
      commentary offers a focus for reflection, discussion and collaborative action.

PMID- 24300331
TI  - Kososan, a standardized traditional Japanese herbal medicine, reverses sleep
      disturbance in socially isolated mice via GABAA-benzodiazepine receptor complex
      activation.
AB  - PURPOSE: Kososan (KSS), a traditional Japanese medicine with a distinct aroma, is
      clinically used to treat affective disorders but its antidepressant-like effect
      has not been thoroughly investigated. In this study, we investigated the effects
      of inhaled and orally administered KSS on sleep disturbances in socially isolated
      mice. METHODS: Four-weeks-old male ddy mice were housed either in social
      isolation or in groups for 4-6 weeks before the experiment. KSS was orally
      administered (0.5 or 1.0 g/kg) or inhaled (0.5, 1.0, or 2.5 g/0.125 m(3)) 60 min
      before pentobarbital administration. Stress levels in mice were evaluated by the
      duration of pentobarbital-induced sleeping time. RESULTS: Sleeping time was
      shorter in socially-isolated mice than in group-housed mice. Oral and inhaled KSS
      prolonged sleeping time in stressed mice, but had no effect on sleeping time of
      group-housed mice. Prolonged sleeping time after oral KSS was significantly
      inhibited (p<0.05) by bicuculline (3 mg/kg, i.p.), a GABAA antagonist, but not by
      flumazenil (3 mg/kg, i.p.), a selective benzodiazepine antagonist. Prolonged
      sleeping time after KSS inhalation was significantly inhibited (p<0.05) by
      flumazenil but not by bicuculline. CONCLUSIONS: Our findings suggest that KSS
      activates GABAA-benzodiazepine receptor complex and reverses shortened
      pentobarbital-induced sleep caused by social isolation.

PMID- 24300332
TI  - The slice culture method for following development of tooth germs in explant
      culture.
AB  - Explant culture allows manipulation of developing organs at specific time points
      and is therefore an important method for the developmental biologist. For many
      organs it is difficult to access developing tissue to allow monitoring during ex
      vivo culture. The slice culture method allows access to tissue so that
      morphogenetic movements can be followed and specific cell populations can be
      targeted for manipulation or lineage tracing. In this paper we describe a method
      of slice culture that has been very successful for culture of tooth germs in a
      range of species. The method provides excellent access to the tooth germs, which
      develop at a similar rate to that observed in vivo, surrounded by the other jaw
      tissues. This allows tissue interactions between the tooth and surrounding tissue
      to be monitored. Although this paper concentrates on tooth germs, the same
      protocol can be applied to follow development of a number of other organs, such
      as salivary glands, Meckel's cartilage, nasal glands, tongue, and ear. 

PMID- 24300333
TI  - Reverse yeast two-hybrid system to identify mammalian nuclear receptor residues
      that interact with ligands and/or antagonists.
AB  - As a critical regulator of drug metabolism and inflammation, Pregnane X Receptor
      (PXR), plays an important role in disease pathophysiology linking metabolism and
      inflammation (e.g. hepatic steatosis)(1,2). There has been much progress in the
      identification of agonist ligands for PXR, however, there are limited
      descriptions of drug-like antagonists and their binding sites on PXR(3,4,5). A
      critical barrier has been the inability to efficiently purify full-length protein
      for structural studies with antagonists despite the fact that PXR was cloned and
      characterized in 1998. Our laboratory developed a novel high throughput yeast
      based two-hybrid assay to define an antagonist, ketoconazole's, binding residues
      on PXR(6). Our method involves creating mutational libraries that would rescue
      the effect of single mutations on the AF-2 surface of PXR expected to interact
      with ketoconazole. Rescue or "gain-of-function" second mutations can be made such
      that conclusions regarding the genetic interaction of ketoconazole and the
      surface residue(s) on PXR are feasible. Thus, we developed a high throughput two
      hybrid yeast screen of PXR mutants interacting with its coactivator, SRC-1. Using
      this approach, in which the yeast was modified to accommodate the study of the
      antifungal drug, ketoconazole, we could demonstrate specific mutations on PXR
      enriched in clones unable to bind to ketoconazole. By reverse logic, we conclude
      that the original residues are direct interaction residues with ketoconazole.
      This assay represents a novel, tractable genetic assay to screen for antagonist
      binding sites on nuclear receptor surfaces. This assay could be applied to any
      drug regardless of its cytotoxic potential to yeast as well as to cellular
      protein(s) that cannot be studied using standard structural biology or proteomic
      based methods. Potential pitfalls include interpretation of data (complementary
      methods useful), reliance on single Y2H method, expertise in handling yeast or
      performing yeast two-hybrid assays, and assay optimization. 

PMID- 24300334
TI  - Congenic fine-mapping identifies a major causal locus for variation in the native
      collateral circulation and ischemic injury in brain and lower extremity.
AB  - RATIONALE: Severity of tissue injury in occlusive disease is dependent on the
      extent (number and diameter) of collateral vessels, which varies widely among
      healthy mice and humans. However, the causative genetic elements are unknown.
      Recently, much of the variation among different mouse strains, including C57Bl/6J
      (B6, high extent) and BALB/cByJ (Bc, low extent), was linked to a quantitative
      trait locus on chromosome 7 (Candq1). OBJECTIVE: We used congenic mapping to
      refine Candq1 and its candidate genes to create an isogenic strain set with large
      differences in collateral extent to assess their impact and the impact of Candq1,
      alone, on ischemic injury. METHODS AND RESULTS: Six congenic strains possessing
      portions of Candq1 introgressed from B6 into Bc were generated and phenotyped.
      Candq1 was refined from 27 to 0.737 Mb with full retention of effect, that is,
      return or rescue of phenotypes from the poor values in Bc to nearly those of wild
      type B6 in the B6/B6 congenic mice as follows: 83% rescue of low pial collateral
      extent and 4.5-fold increase in blood flow and 85% reduction of infarct volume
      after middle cerebral artery occlusion; 54% rescue of low skeletal muscle
      collaterals and augmented recovery of perfusion (83%) and function after femoral
      artery ligation. Gene deletion and in silico analysis further delineated the
      candidate genes. CONCLUSIONS: We have significantly refined Candq1 (now
      designated determinant of collateral extent 1; Dce1), demonstrated that genetic
      background-dependent variation in collaterals is a major factor underlying
      differences in ischemic tissue injury, and generated a congenic strain set with
      wide allele dose-dependent variation in collateral extent for use in
      investigations of the collateral circulation.

PMID- 24300335
TI  - Infinium assay for large-scale SNP genotyping applications.
AB  - Genotyping variants in the human genome has proven to be an efficient method to
      identify genetic associations with phenotypes. The distribution of variants
      within families or populations can facilitate identification of the genetic
      factors of disease. Illumina's panel of genotyping BeadChips allows investigators
      to genotype thousands or millions of single nucleotide polymorphisms (SNPs) or to
      analyze other genomic variants, such as copy number, across a large number of DNA
      samples. These SNPs can be spread throughout the genome or targeted in specific
      regions in order to maximize potential discovery. The Infinium assay has been
      optimized to yield high-quality, accurate results quickly. With proper setup, a
      single technician can process from a few hundred to over a thousand DNA samples
      per week, depending on the type of array. This assay guides users through every
      step, starting with genomic DNA and ending with the scanning of the array. Using
      propriety reagents, samples are amplified, fragmented, precipitated, resuspended,
      hybridized to the chip, extended by a single base, stained, and scanned on either
      an iScan or Hi Scan high-resolution optical imaging system. One overnight step is
      required to amplify the DNA. The DNA is denatured and isothermally amplified by
      whole-genome amplification; therefore, no PCR is required. Samples are hybridized
      to the arrays during a second overnight step. By the third day, the samples are
      ready to be scanned and analyzed. Amplified DNA may be stockpiled in large
      quantities, allowing bead arrays to be processed every day of the week, thereby
      maximizing throughput. 

PMID- 24300336
TI  - Associations between host characteristics and antimicrobial resistance of
      Salmonella typhimurium.
AB  - A collection of Salmonella Typhimurium isolates obtained from sporadic
      salmonellosis cases in humans from Lower Saxony, Germany between June 2008 and
      May 2010 was used to perform an exploratory risk-factor analysis on antimicrobial
      resistance (AMR) using comprehensive host information on sociodemographic
      attributes, medical history, food habits and animal contact. Multivariate
      resistance profiles of minimum inhibitory concentrations for 13 antimicrobial
      agents were analysed using a non-parametric approach with multifactorial models
      adjusted for phage types. Statistically significant associations were observed
      for consumption of antimicrobial agents, region type and three factors on egg
      purchasing behaviour, indicating that besides antimicrobial use the proximity to
      other community members, health consciousness and other lifestyle-related
      attributes may play a role in the dissemination of resistances. Furthermore, a
      statistically significant increase in AMR from the first study year to the second
      year was observed.

PMID- 24300337
TI  - Three decades of research at Flakaliden advancing whole-tree physiology, forest
      ecosystem and global change research.
AB  - Nutrient supply often limits growth in forest ecosystems and may limit the
      response of growth to an increase in other resources, or to more favorable
      environmental factors such as temperature and soil water. To explore the
      consequences and mechanisms of optimum nutrient supply for forest growth, the
      Flakaliden research site was established in 1986 on a young Norway spruce site
      with nutrient-poor soil. This special section on research at Flakaliden presents
      five papers that explore different facets of nutrition, atmospheric CO2
      concentration, [CO2], and increased temperature treatments, using the original
      experiment as a base. Research at Flakaliden shows the dominant role of nutrition
      in controlling the response of growth to the increased photosynthesis promoted by
      elevated [CO2] and temperature. Experiments with whole-tree chambers showed that
      all treatments (air temperature warming, elevated [CO2] and optimum nutrition)
      increased shoot photosynthesis by 30-50%, but growth only increased with [CO2]
      when combined with the optimum nutrition treatment. Elevated [CO2] and
      temperature increased shoot photosynthesis by increasing the slope between light
      saturated photosynthesis and foliar nitrogen by 122%, the initial slope of the
      light response curve by 52% and apparent quantum yield by 10%. Optimum nutrition
      also decreased photosynthetic capacity by 17%, but increased it by 62% in
      elevated [CO2], as estimated from wood delta(13)C. Elevated air temperature
      advanced spring recovery of photosynthesis by 37%, but spring frost events
      remained the controlling factor for photosynthetic recovery, and elevated [CO2]
      did not affect this. Increased nutrient availability increased wood growth
      primarily through a 50% increase in tracheid formation, mostly during the peak
      growth season. Other notable contributions of research at Flakaliden include
      exploring the role of optimal nutrition in large-scale field trials with foliar
      analysis, using an ecosystem approach for multifactor experiments, development of
      whole-tree chambers allowing inexpensive environmental manipulations, long-term
      deployment of shoot chambers for continuous measurements of gas exchange and
      exploring the ecosystem response to soil and aboveground tree warming. The
      enduring legacy of Flakaliden will be the rich data set of long-term, multifactor
      experiments that has been and will continue to be used in many modeling and cross
      site comparison studies.

PMID- 24300338
TI  - Calcium and aluminum impacts on sugar maple physiology in a northern hardwood
      forest.
AB  - Forests of northeastern North America have been exposed to anthropogenic acidic
      inputs for decades, resulting in altered cation relations and disruptions to
      associated physiological processes in multiple tree species, including sugar
      maple (Acer saccharum Marsh.). In the current study, the impacts of calcium (Ca)
      and aluminum (Al) additions on mature sugar maple physiology were evaluated at
      the Hubbard Brook Experimental Forest (Thornton, NH, USA) to assess remediation
      (Ca addition) or exacerbation (Al addition) of current acidified conditions. Fine
      root cation concentrations and membrane integrity, carbon (C) allocation, foliar
      cation concentrations and antioxidant activity, foliar response to a spring
      freezing event and reproductive ability (flowering, seed quantity, filled seed
      and seed germination) were evaluated for dominant sugar maple trees in a
      replicated plot study. Root damage and foliar antioxidant activity were highest
      in Al-treated trees, while growth-associated C, foliar re-flush following a
      spring frost and reproductive ability were highest in Ca-treated trees. In
      general, we found that trees on Ca-treated plots preferentially used C resources
      for growth and reproductive processes, whereas Al-treated trees devoted C to
      defense-based processes. Similarities between Al-treated and control trees were
      observed for foliar cation concentrations, C partitioning and seed production,
      suggesting that sugar maples growing in native forests may be more stressed than
      previously perceived. Our experiment suggests that disruption of the balance of
      Ca and Al in sugar maples by acid deposition continues to be an important driver
      of tree health.

PMID- 24300339
TI  - Exposure to low- vs iso-osmolar contrast agents reduces NADPH-dependent reactive
      oxygen species generation in a cellular model of renal injury.
AB  - Contrast-induced nephropathy represents the third cause of hospital-acquired
      acute renal failure. This study investigated the effects of low- vs iso-osmolar
      contrast medium (CM) exposure on NADPH-dependent reactive oxygen species (ROS)
      generation by tubular cells. X-ray attenuation of iohexol, iopamidol, and
      iodixanol was assessed at equimolar iodine concentrations and their effects on
      human renal proximal tubular cells (PTCs) were evaluated with equally attenuating
      solutions of each CM. Cytotoxicity, apoptosis, and necrosis were investigated by
      trypan blue exclusion, MTT assay, and annexin V/propidium iodide assay,
      respectively. ROS production was assessed by DCF assay, NADPH oxidase activity by
      the lucigenin-enhanced chemiluminescence method, and Nox4 expression by
      immunoblot. Yielding the same X-ray attenuation, CM cytotoxicity was assessed in
      PTCs at equimolar iodine concentrations. More necrosis was present after
      incubation with iohexol and iopamidol than after incubation with equal
      concentrations of iodixanol. Iohexol and iodixanol at low iodine concentrations
      induced less cytotoxicity than iopamidol. Moreover, both iohexol and iopamidol
      induced more apoptosis than iodixanol, with a dose-dependent effect. ROS
      generation was significantly higher with iopamidol and iohexol compared to
      iodixanol. NADPH oxidase activity and Nox4 protein expression significantly
      increased after exposure to iopamidol and iohexol, with a dose-dependent effect,
      compared with iodixanol. CM-induced Nox4 expression and activity depended upon
      Src activation. In conclusion, at angiographic concentrations, iodixanol induces
      fewer cytotoxic effects on cultured tubular cells than iohexol and iopamidol
      along with a lower induction of Nox4-dependent ROS generation. This enzyme may,
      thus, represent a potential therapeutic target to prevent iodinated CM-related
      oxidative stress. 

PMID- 24300340
TI  - Skin dose measurements using radiochromic films, TLDS and ionisation chamber and
      comparison with Monte Carlo simulation.
AB  - Estimation of the surface dose is very important for patients undergoing
      radiation therapy. The purpose of this study is to investigate the dose at the
      surface of a water phantom at a depth of 0.007 cm as recommended by the
      International Commission on Radiological Protection and International Commission
      on Radiation Units and Measurement with radiochromic films (RFs),
      thermoluminescent dosemeters and an ionisation chamber in a 6-MV photon beam. The
      results were compared with the theoretical calculation using Monte Carlo (MC)
      simulation software (MCNP5, BEAMnrc and DOSXYZnrc). The RF was calibrated by
      placing the films at a depth of maximum dose (d(max)) in a solid water phantom
      and exposing it to doses from 0 to 500 cGy. The films were scanned using a
      transmission high-resolution HP scanner. The optical density of the film was
      obtained from the red component of the RGB images using ImageJ software. The per
      cent surface dose (PSD) and percentage depth dose (PDD) curve were obtained by
      placing film pieces at the surface and at different depths in the solid water
      phantom. TLDs were placed at a depth of 10 cm in a solid water phantom for
      calibration. Then the TLDs were placed at different depths in the water phantom
      and were exposed to obtain the PDD. The obtained PSD and PDD values were compared
      with those obtained using a cylindrical ionisation chamber. The PSD was also
      determined using Monte Carlo simulation of a LINAC 6-MV photon beam. The
      extrapolation method was used to determine the PSD for all measurements. The PSD
      was 15.0+/-3.6% for RF. The TLD measurement of the PSD was 16.0+/-5.0%. The (0.6
      cm(3)) cylindrical ionisation chamber measurement of the PSD was 50.0+/-3.0%. The
      theoretical calculation using MCNP5 and DOSXYZnrc yielded a PSD of 15.0+/-2.0%
      and 15.7+/-2.2%. In this study, good agreement between PSD measurements was
      observed using RF and TLDs with the Monte Carlo calculation. However, the
      cylindrical chamber measurement yielded an overestimate of the PSD. This is
      probably due to the ionisation chamber calibration factor that is only valid in
      charged particle equilibrium condition, which is not achieved at the surface in
      the build-up region.

PMID- 24300341
TI  - Prediction of background in low-energy spectrum of Phoswich detector.
AB  - In vivo monitoring of actinides in occupational workers is done using Phoswich
      detector by measuring the low-energy X ray and gamma rays. Quantification of
      actinides like plutonium and americium in the lungs is extremely difficult due to
      higher background in the low-energy regions, which is from ambient background as
      well as from the subject. In the latter case, it is mainly due to the Compton
      scattering of body potassium, which varies person-to-person. Hence, an accurate
      prediction of subject-specific background counts in the lower-energy regions is
      an essential element in the in vivo measurement of plutonium and americium.
      Empirical equations are established for the prediction of background count rate
      in (239)Pu and (241)Am lower-energy regions, called 'target regions', as a
      function of count rate in the monitoring region (97-130 keV)/(40)K region in the
      high-energy spectrum, weight-to-height ratio of the subject (scattering
      parameter) and the gender. 

PMID- 24300342
TI  - Process of making three-dimensional microstructures using vaporization of a
      sacrificial component.
AB  - Vascular structures in natural systems are able to provide high mass transport
      through high surface areas and optimized structure. Few synthetic material
      fabrication techniques are able to mimic the complexity of these structures while
      maintaining scalability. The Vaporization of a Sacrificial Component (VaSC)
      process is able to do so. This process uses sacrificial fibers as a template to
      form hollow, cylindrical microchannels embedded within a matrix. Tin (II) oxalate
      (SnOx) is embedded within poly(lactic) acid (PLA) fibers which facilitates the
      use of this process. The SnOx catalyzes the depolymerization of the PLA fibers at
      lower temperatures. The lactic acid monomers are gaseous at these temperatures
      and can be removed from the embedded matrix at temperatures that do not damage
      the matrix. Here we show a method for aligning these fibers using micromachined
      plates and a tensioning device to create complex patterns of three-dimensionally
      arrayed microchannels. The process allows the exploration of virtually any
      arrangement of fiber topologies and structures. 

PMID- 24300343
TI  - Video-assisted ablation of pilonidal sinus: a new minimally invasive treatment--a
      pilot study.
AB  - BACKGROUND: We hypothesized that video-assisted ablation of pilonidal sinus could
      be an effective, minimally invasive treatment of pilonidal sinus. This new,
      minimally invasive treatment allows the identification of the sinus cavity with
      its lateral tracks, destruction and the removal of all infected tissue, and the
      removal of any hair. STUDY DESIGN: All consecutive patients with primary
      sacrococcygeal pilonidal sinus were screened for enrolment in our study. We
      analyzed time off work, time to walk without pain, time to sitting on the toilet
      without pain, recurrences, wound infections, and patient satisfaction (pain,
      health status, and aesthetic appearance). RESULTS: We analyzed 27 patients. All
      procedures were successful, with complete ablation of the sinus cavity. No
      infection and only 1 recurrence were recorded during the follow-up (1 year) with
      an immediate return to work and normal activities. In addition, patient
      satisfaction and aesthetic appearance were high. CONCLUSION: Our results are
      encouraging and suggest that this technique may offer a very effective way to
      treat pilonidal sinus. Further studies are necessary to validate its use in daily
      practice.

PMID- 24300344
TI  - Unusual site of metastasis detected with FDG PET/CT in a case of recurrent
      rectosigmoid cancer.
AB  - Metastatic colon cancers to the oral cavity are unusual, involving a majority of
      the mandible rather than the oral soft tissues. We describe a rare site of
      gingival metastasis in a case of rectosigmoid cancer. The patient was a 74-year
      old woman who developed swelling and persistent bleeding of the right mandibular
      gingiva after tooth extraction. A PET/CT using 18F-FDG depicted multiple
      metastatic lesions in the neck, lung, abdominal wall, and mandibular gingiva.
      Histologic study of the gingival lesion confirmed the diagnosis of gingival
      metastasis from colon adenocarcinoma.

PMID- 24300345
TI  - Therapeutic status-dependent thymic changes on 18F-FDG PET/CT in an adult patient
      with lymphoma who underwent 2 phases of chemotherapy.
AB  - A 31-year-old woman who underwent 2 phases of chemotherapy for Hodgkin lymphoma
      subsequently underwent 8 F-FDG PET/CT scans for staging and treatment response
      evaluation. The images revealed that the Hounsfield unit and SUV of the thymus
      changed with the therapeutic status; both decreased to the lowest level 0.5
      months after chemotherapy and increased to the highest level 8 to 12 months after
      the end of treatment. Interestingly, we found a positive correlation between the
      thymic Hounsfield unit and SUV, with a Spearman correlation coefficient of 0.946
      (P < 0.001). 

PMID- 24300346
TI  - 18F-FDG PET/CT and MR findings of ovarian carcinoid within a dermoid cyst.
AB  - Ovarian carcinoid is a rare neoplasm of low-grade malignancy occurring within a
      dermoid cyst or mucinous tumor, predominantly in perimenopausal women. Reports
      with radiologic features are scarce. We present a case of a 57-year-old woman
      with an ovarian carcinoid within a dermoid cyst manifested as a multilocular
      cystic mass with a solid component showing 18F-FDG PET uptake (SUVmax=6.02).

PMID- 24300347
TI  - Role of 18F-DOPA PET/CT in diagnosis and follow-up of adrenal and extra-adrenal
      paragangliomas.
AB  - PURPOSE: The objective of this study was to establish the clinical value of F
      DOPA PET/CT in patients with adrenal and extra-adrenal paragangliomas (PGLs).
      METHODS: Twenty-six consecutive patients with suspected or recurrent PGL
      underwent MR (and/or CT) and F-DOPA PET/CT. Histopathology confirmation was
      obtained in 20 cases. Genetic analysis on known susceptibility genes for PGL
      (VHL, RET, SDHx, TMEM127) was available in 13 patients. RESULTS: Fourteen
      patients were affected by PGL (8 with head/neck location, 6 with
      abdominal/thoracic location), whereas 12 showed masses of other origin. Three
      patients proved to be SDHD, 1 SDHB, 2 SDHC, and 1 TMEM127 mutation carriers. F
      DOPA PET/CT showed pathological uptake in 13 of 26 patients. The procedure
      identified all PGLs except one with bone metastases (previous malignant adrenal
      PGL). No uptake was found in patients without proven PGL. Thus, in the whole
      group, F-DOPA PET/CT sensitivity was 92.8%, and specificity was 100% with
      positive and negative predictive values of 100% and 92.3%, respectively. Total
      diagnostic accuracy was 96.2%. In the head/neck subgroup, sensitivity,
      specificity, positive and negative predictive values, and diagnostic accuracy
      were 100%. In the abdominal location, sensitivity was 80% and specificity was
      100%, and positive and negative predictive values were 100% and 91.7%,
      respectively. Abdominal diagnostic accuracy was 93.7%. Radiotracer uptake was
      superimposable in head/neck PGLs versus abdominal PGLs and in mutated versus wild
      type patients. CONCLUSIONS: The high diagnostic performance of F-DOPA PET/CT
      showed this technique to be a useful tool in detecting PGLs, above all those
      located at the head/neck site, regardless of the genetic pattern.

PMID- 24300348
TI  - A rare case of pulmonary malignant granular cell tumor detected with 18F-FDG
      PET/CT imaging.
AB  - Malignant granular cell tumor is rarely involved in the lungs. We present a rare
      case with 18F-FDG PET/CT images showing a hypermetabolic lesion in the lower lobe
      of the left lung with posterior mediastinum invasion. Histopathologic study
      proved it as malignant granular cell tumor.

PMID- 24300349
TI  - (18)F-FDG PET/CT findings of obstructive colitis proximal to colorectal cancer.
AB  - PURPOSE: This study was performed to determine the frequency and patterns of
      obstructive colitis (OC) seen on F-FDG PET/CT scan of patients with
      adenocarcinoma of the colon and rectum. PATIENTS AND METHODS: Preoperative PET/CT
      scans and surgical records of 308 patients with surgically proven colorectal
      adenocarcinoma were retrospectively reviewed for the presence of colon
      obstruction and OC proximal to the colorectal adenocarcinoma. The distributions,
      patterns, and SUVmax of OC were evaluated on PET/CT. Abdominal CT, colonoscopic
      finding, and histopathologic findings of surgical specimen were also reviewed.
      RESULTS: Of 308 patients, PET/CT scans of 29 (9.4%) showed OC. The mean SUVmax of
      OC was 3.6 +/- 2.2 (range, 1.6-12.3). Obstructive colitis was contiguous to the
      tumor in 23 patients (79.3%) and noncontiguous in 6 (20.7%). Obstructive colitis
      was diffuse in 25 patients (86%) and patchy in 4 (14%). It was segmental in 16
      patients (55%) and pancolonic in 13 (45%). Twenty-three of 29 patients (79.3%)
      showed proximal wall thickening to colon cancer on abdominal CT performed about 3
      days before PET/CT.The patients with OC on PET/CT was significantly associated
      with annular (P = 0.017), large-sized (P < 0.001), and advanced colon cancer (P <
      0.001). However, there was no association between tumor size and SUVmax of OC.Ten
      proximal polyps were detected in 7 of 29 patients (24.1%) on colonoscopy and
      surgical specimen. Of these, 1 proximal polyp was removed before PET/CT scan,
      whereas the remaining 9 were not detected on PET/CT scan. CONCLUSIONS:
      Obstructive colitis is predominantly diffuse and contiguous with the obstructing
      adenocarcinoma. Colorectal cancer with OC tends to show annular shape and larger
      tumor size. Obstructive colitis may lower the possibility of detection of
      synchronous proximal colonic lesion by PET/CT.

PMID- 24300350
TI  - Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw.
AB  - This study evaluates the diagnostic utility of 3-phase bone scintigraphy for
      diagnosing osteoradionecrosis of the jaw (ORNJ). METHODS: Thirty-two consecutive
      patients with a history of radiation to the head and neck region (range, 62-70
      Gy; mean, 68 Gy; median, 69 Gy) due to squamous cell cancer and suspected ORNJ
      underwent 3-phase bone scans after injection of 520 to 750 MBq of Tc-MPD. In
      addition to planar scans, tomographic images (SPECT) were acquired in the second
      phase and SPECT/CT images during the third phase. Histopathologic findings (n =
      18) and clinical follow-up (n = 14) served as reference standard for
      osteoradionecrosis. RESULTS: The first, second, and third phases of planar images
      were rated positive in 18/32 patients (56.3%), 25/32 (78.1%), and 27/32 patients
      (84.4%), respectively. The late SPECT was positive in all patients (32/32, 100%),
      respectively. Histopathologic findings available in 18/32 patients (56.3%)
      confirmed ORNJ in all subjects. Acute inflammation was histologically proven in
      18/18 specimens (100%) and additional chronic inflammation in 12/18 (66.7%). In
      13/18 (72.2%) specimens, superinfection was evident histopathologically. A
      photopenic defect with surrounding hypermetabolism, a reported hallmark of ORJN,
      was found in less than 5%. CONCLUSIONS: The predominant scintigraphic pattern of
      osteoradionecrosis includes increased bone mineralization phase in all patients.
      Central photopenia, reportedly a typical bone scan finding in bisphosphonate
      induced osteonecrosis, was not characteristic for ORNJ. A differentiation of
      acute from chronic inflammatory processes was not possible.

PMID- 24300351
TI  - (99m)Tc-MIBI emboli in the lungs detected on SPECT/CT: a pitfall in parathyroid
      scan.
AB  - Although we are familiar with artifactual, focal pulmonary F-FDG accumulations
      without an apparent underlying pathologic finding, similar artifact for Tc-MIBI
      has not been described yet. Herein, we reported incidental detection of Tc-MIBI
      emboli in the lungs on parathyroid SPECT/CT. 

PMID- 24300352
TI  - Biological target volume overlapping segmentation system method for avoiding
      false-positive PET findings in assessing response to neoadjuvant chemoradiation
      therapy in rectal cancer.
AB  - PURPOSE: FDG PET/CT has a recognized high predictive power to assess the response
      to neoadjuvant chemoradiation therapy (CRT) in patients affected by locally
      advanced rectal cancer (LARC), but a relatively high number of false-positive
      findings decrease its specificity: with the aim to solve this problem, a new
      method of imaging analysis is here proposed. METHODS: The new method here
      described, named Biological target volume (BTV) Overlapping Segmentation System
      (BOSS), has been applied on 24 consecutive patients with LARC that were all
      previously classified as nonresponders to CRT by means of the response index
      criterion that is adopted in our center. The BOSS method is based on the
      quantification of the amount of superimposition between pretreatment and
      posttreatment BTV. All BTVpre was down using a threshold of 60% of SUVmax in the
      tumor (BTV60). The results (overlap volumes and percentage of overlap volumes)
      were then matched up with postoperative pathology classified by the Mandard's
      tumor regression grade (TRG) system. RESULTS: Eleven patients were classified as
      responders (TRG1-2) and 13 as nonresponders (TRG 3-5). Among all the results
      obtained by BOSS method, only the percentage of overlap volume data between BTV60
      and BTVpost (%Over_60) was able to correctly distinguish between responders and
      nonresponders. In our experience, a cutoff of 56% on the %Over_60 provided the
      best results in terms of true negative (11 cases), true positive (12 cases),
      false negative (1 case), and false positive (none). CONCLUSIONS: This new method,
      we developed, appears able to unmask the false-positive cases, improving the
      specificity of FDG PET/CT to predict the response to CRT patients with LARC.

PMID- 24300353
TI  - SPECT/CT imaging of retroperitoneal extraskeletal osteosarcoma.
AB  - The condition of a 52-year-old man was diagnosed with unresectable
      retroperitoneal extraskeletal osteosarcoma. SPECT/CT demonstrated a
      retroperitoneal extraskeletal osteosarcoma adjacent to the right upper ureter
      with large calcifications and increased Tc-MDP accumulation. Multiple hepatic
      capsular, renal fascial, and peritoneal metastases were noted. Four months later,
      multiple peritoneal metastases were noted at the second-look surgery. A
      histopathologic examination confirmed osteosarcoma. 

PMID- 24300354
TI  - Increased FDG uptake in scrotal steatocystoma multiplex with calcification.
AB  - Steatocystoma multiplex is a rare, benign, sporadic or familial disorder.
      Steatocystoma multiplex with extensive calcification is extremely rare. A 57-year
      old man presented fever and cough with expectoration for 3 weeks. Chest CT showed
      bilateral pleural effusion. FDG PET/CT showed diffuse FDG uptake of the bone
      marrow and multiple hypermetabolic calcified nodules in the scrotum with SUVmax
      of 7.6. Blood culture revealed septicemia. Skin biopsy of the scrotal nodules
      revealed steatocystoma multiplex with calcification. Histopathologically, there
      were rich multinucleated giant cells and lymphocytes in the cyst wall of the
      steatocystoma, which may contribute to the increased FDG uptake. 

PMID- 24300355
TI  - Enhanced CT and FDG PET/CT in primary malignant peripheral nerve sheath tumor of
      the uterine cervix.
AB  - Malignant peripheral nerve sheath tumor of the uterine cervix is extremely rare.
      A 45-year-old woman presented with intermittent vaginal bleeding for 1 month.
      Enhanced CT in the arterial and venous phases showed a hypervascular tumor in the
      uterine cervix. Colposcopy-directed biopsy revealed malignant peripheral nerve
      sheath tumor. FDG PET/CT showed intense FDG uptake (SUVmax, 8.8) of the tumor
      mimicking cervical cancer. Total laparoscopic radical hysterectomy, bilateral
      salpingo-oophorectomy, and pelvic lymphadenectomy were performed. 

PMID- 24300356
TI  - FDG PET/CT in primary pulmonary lymphoepithelioma-like carcinoma.
AB  - Primary pulmonary lymphoepithelioma-like carcinomas are extremely rare tumors
      with better prognosis than other types of non-small cell lung cancer. An 83-year
      old man presented with cough and hemoptysis for 2 weeks. Chest CT images showed a
      cylinder-shaped lesion in the right upper lung. F-FDG PET/CT showed strong FDG
      uptake (SUVmax, 34.5) of the tumor with ipsilateral hilar lymph node metastases.
      Video-assisted thoracoscopic lobectomy was performed. Histopathologically, the
      tumor was composed of epithelial tumor cells with high proliferation index (80%)
      and abundant lymphoplasmacytic cells, consistent with lymphoepithelioma-like
      carcinoma. 

PMID- 24300357
TI  - Tips for a physician in getting the right job, part VII: behavioral questions for
      an executive interview.
AB  - In addition to general interview questions, the applicant for an administrative
      position may be asked behavioral questions. It is possible to prepare for
      behavioral interview questions partly through research to find out what the
      employer wants and then doing a self-inventory to determine what can best
      illustrate that the candidate has those attributes. It is also helpful to review
      likely questions and to rehearse the answers. Many behavioral questions, several
      of which have hints regarding the answers, are included in this article. 

PMID- 24300358
TI  - Glioblastoma multiforme metastastic to the bone: diagnosis by (18)F-NaF PET/CT.
AB  - Extracranial metastases from glioblastoma multiforme (GBM) are rare. We report a
      case of osseous metastases from GBM diagnosed by F-NaF PET/CT. A 30-year-old man
      with a history of GBM presented with bone pain and underwent F-NaF PET/CT for
      further evaluation. On PET/CT, intense uptake in 2 bone lesions was noted.
      Histopathologic evaluation revealed osseous metastases from GBM. Although rare,
      bone metastases have to be considered in patients with axial tumors and
      atraumatic bone pain. F-NaF PET/CT is a highly sensitive and valuable tool for
      detection of osseous metastases. 

PMID- 24300359
TI  - Increased 18F-FDG uptake by a retroperitoneal mature cystic teratoma in an
      infant.
AB  - A teratoma is a nonseminomatous germ cell tumor composed of well-differentiated
      derivations from at least 2 of the 3 germ layers. Mature cystic teratomas are
      known to have low metabolic activity and do not exhibit increased FDG uptake on
      PET. We report a case of mature cystic teratoma of the retroperitoneum showing
      increased FDG uptake in the solid portion. Pathologically, the solid portion was
      composed of abundant central nervous tissue. Increased FDG uptake in a teratoma
      may be not only due to an immature or malignant component but also to the
      presence of central nervous tissue. 

PMID- 24300360
TI  - FDG PET/CT detection of intussusception caused by lymphoma in a pediatric
      patient.
AB  - A previously healthy 9-year-old boy presented to an outside hospital with a
      history of abdominal pain and vomiting. An abdominal x-ray was unremarkable. A CT
      of the abdomen and pelvis performed to evaluate possible obstruction after weight
      loss and vomiting over a 3-week period demonstrated a large retroperitoneal mass.
      Laparoscopic biopsy showed diffuse large B-cell lymphoma. FDG PET/CT was
      performed for staging. An ileocolic intussusception was identified on the PET/CT.
      The intussusception was successfully managed with medical treatment. We present
      FDG PET/CT findings in intussusception with non-Hodgkin lymphoma as the lead
      point in a pediatric patient. 

PMID- 24300361
TI  - Effect of radioactive iodine therapy on lacrimal gland functions in patients with
      hyperthyroidism.
AB  - BACKGROUND: Radioactive iodine (RAI) therapy is preferred in the treatment of
      hyperthyroidism because of its effectiveness, noninvasiveness, and low costs. I
      has been detected in extrathyroidal tissues, such as in gastric mucosa, salivary
      glands, and lacrimal glands. To the best of our knowledge, there is no
      publication concerning the effects of RAI therapy for hyperthyroidism on tear
      production. In the present study, we evaluated whether or not the lacrimal glands
      are affected after RAI therapy when compared with pretreatment period. METHODS:
      The Schirmer and tear break-up time (TBUT) tests were used to assess 32 eyes of
      16 patients with conditions that were diagnosed as hyperthyroidism before and at
      3 and 6 months after RAI treatment. In addition, pretreatment values of patients
      were compared with that of controls. It was evaluated whether or not a
      correlation exists between the results and the dose or iodine uptake values.
      RESULTS: There was no significant difference between pretreatment values of
      Schirmer and TBUT tests obtained in the patient group and those of the control
      group (P > 0.05). In the patient group, there was a significant difference
      between the posttreatment and pretreatment values (P < 0.05). There was a
      positive correlation between uptake values obtained at 24 hours and the values
      obtained by TBUT and Schirmer tests on both eyes at 3 and 6 months. At 6 months,
      the uptake value at 24 hours was 28.83 +/- 60 for both eyes in patients with TBUT
      test values less than 10, whereas it was 39.25 +/- 7.88 for the right eye and
      39.00 +/- 6.85 for the left eyes in patients with TBUT test values greater than
      10. The difference was statistically significant (P < 0.05). CONCLUSIONS: In our
      study, we concluded that the decrease in mucin and aqueous production occurs due
      to affected lacrimal glands by RAI therapy; however, this effect is not dose
      dependent.

PMID- 24300362
TI  - (131)I SPECT/CT demonstrated ovarian endometrioma.
AB  - A 44-year-old woman had a history of papillary thyroid carcinoma and underwent
      total thyroidectomy and I ablation therapy. During the follow-up, 2-mCi I cancer
      workup showed an unusual shape of uptake in the pelvic region. Hybrid SPECT/CT
      revealed uptake posterior to the uterus, where sonography showed an 85.4-mm right
      ovarian endometrioma just corresponding to the location. Laparoscopic salpingo
      oophorectomy showed right ovarian endometrioma (7 cm) and left ovarian cyst (4
      cm). Pathologic findings showed bilateral endometriosis. After that survey,
      follow-up I cancer workup showed left supraclavicular, pretracheal, and right
      hilar metastatic lymphadenopathy with pulmonary metastasis, but no pelvic uptake
      was noted. 

PMID- 24300363
TI  - Os vesalianum pedis detected with bone SPECT/CT.
AB  - We present an 18-year-old man with pain at the lateral aspect of his left foot.
      Radiograph showed abnormal ossicle in the proximal aspect of the left fifth
      metatarsal tuberosity, which was articulated with the fifth metatarsal and cuboid
      bones. Bone scintigraphy and SPECT/CT demonstrated increased uptakes at the
      ossicles in the proximal aspect of both fifth metatarsal bones. CT revealed that
      the ossicle and the adjacent bones have well-corticated margins. The diagnosis
      was os vesalianum, a rare accessory bone of the foot. We have reported the
      SPECT/CT bone scan findings of the os vesalianum.

PMID- 24300364
TI  - Complete and readily reversible blocking of striatal DaTscan binding by
      methylphenidate.
AB  - An 80-year-old man with Parkinson disease underwent DaTscan imaging, which showed
      no detectable uptake in the basal ganglia but normal background uptake in other
      parts of the brain and in the chest and abdomen. It was later found that the
      patient was taking methylphenidate. The second study performed 3 weeks later
      after discontinuing methylphenidate for 48 hours showed good uptake in the
      striatum. Our results indicate that methylphenidate may completely block
      physiologic uptake of DaTscan in the striatum and that this effect can be
      effectively reversed after discontinuing the medication for a short period. 

PMID- 24300365
TI  - Migrating tumor thrombus trapped within the greenfield filter of the inferior
      vena cava and depicted by FDG PET/CT.
AB  - A 72-year-old woman with leiomyosarcoma of the left thigh underwent a whole-body
      FDG PET/CT for staging, which demonstrated a large FDG-avid tumor in the left
      thigh and tumor thrombosis involving the profunda femoris artery/vein and
      superior femoral vein. A Greenfield filter was placed in the inferior vena cava
      before the radical resection of the tumor and thrombosis. Postoperative PET/CT
      showed an FDG-avid embolus trapped within the solid apical cap of the filter in
      the inferior vena cava. It was unknown if the tumor embolus migrated to the
      inferior vena cava before or during the surgical procedure of radical resection. 

PMID- 24300366
TI  - Compaction behavior of isomalt after roll compaction.
AB  - The suitability of the new isomalt grade galenIQ&trade; 801 for dry granulation
      and following tableting is evaluated in this study. Isomalt alone, as well as a
      blend of equal parts with dibasic calcium phosphate, is roll compacted and
      tableted. Particle size distribution and flowability of the granules and
      friability and disintegration time of the tablets are determined. Tensile
      strength of tablets is related to the specific compaction force during roll
      compaction and the tableting force. In all cases, the tensile strength increases
      with raising tableting forces. The specific compaction force has a different
      influence. For isomalt alone the tensile strength is highest for tablets made
      from granules prepared at 2 kN/cm and 6 kN/cm and decreases at higher values,
      i.e., >10 kN/cm. Tensile strength of the blend tablets is almost one third lower
      compared to the strongest tablets of pure isomalt. Friability of pure isomalt
      tablets is above the limit. Disintegration time is longest when the tensile
      strength is at its maximum and decreases with higher porosity and lower tensile
      strengths. Isomalt proves to be suitable for tableting after roll compaction.
      Even though the capacity as a binder might not be as high as of other excipients,
      it is a further alternative for the formulation scientist. 

PMID- 24300367
TI  - Development strategies for herbal products reducing the influence of natural
      variance in dry mass on tableting properties and tablet characteristics.
AB  - One "Quality by Design" approach is the focus on the variability of the
      properties of the active substance. This is crucially important for active
      substances that are obtained from natural resources such as herbal plant material
      and extracts. In this paper, we present various strategies for the development of
      herbal products especially taking into account the natural batch-to-batch
      variability (mainly of the dry mass) of tablets that contain a fixed amount of
      tincture. The following steps in the development have been evaluated for the
      outcome of the physico-chemical properties of the resulting tablets and
      intermediates: concentration of the tincture extracted from Echinacea fresh
      plant, loading of the concentrate onto an inert carrier, the respective wet
      granulation and drying step, including milling, and the adjuvant excipients for
      the tablet compression step. The responses that were investigated are the mean
      particle size of the dried and milled granulates, compaction properties and
      disintegration time of the tablets. Increased particle size showed a significant
      increase of the disintegration time and a decrease of the compaction properties.
      In addition, our results showed that the particle size has a great dependency on
      the ratio of liquid to carrier during the wet granulation process. Thus, the
      variability of the respective parameters tested was influenced by the performed
      strategies, which is how the tincture correlated to its dry mass and the relation
      of the amount of carrier used. In order to optimize these parameters, a strategy
      considering the above-mentioned points has to be chosen. 

PMID- 24300368
TI  - Bioavailability of a lipidic formulation of curcumin in healthy human volunteers.
AB  - Numerous publications have reported the significant pharmacodynamic activity of
      Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the
      present study was to perform a detailed pharmacokinetic evaluation of CRM after
      the oral administration of a highly bioavailable lipidic formulation of CRM (CRM
      LF) in human subjects. Cmax, Tmax and AUC0-Y were found to be 183.35 +/- 37.54
      ng/mL, 0.60 +/- 0.05 h and 321.12 +/- 25.55 ng/mL respectively, at a dose of 750
      mg. The plasma profile clearly showed three distinct phases, viz., absorption,
      distribution and elimination. A close evaluation of the primary pharmacokinetic
      parameters provided valuable insight into the behavior of the CRM after
      absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min).
      Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model
      with first order absorption, lag time and first order elimination. A high
      absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid
      absorption of the CRM into the central compartment. This was followed by the
      distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The
      rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was
      slow. This encourages higher tissue levels of CRM as compared with plasma levels.
      The study provides an explanation of the therapeutic efficacy of CRM, despite
      very low/undetectable levels in the plasma. 

PMID- 24300369
TI  - Artificial neural networks in evaluation and optimization of modified release
      solid dosage forms.
AB  - Implementation of the Quality by Design (QbD) approach in pharmaceutical
      development has compelled researchers in the pharmaceutical industry to employ
      Design of Experiments (DoE) as a statistical tool, in product development. Among
      all DoE techniques, response surface methodology (RSM) is the one most frequently
      used. Progress of computer science has had an impact on pharmaceutical
      development as well. Simultaneous with the implementation of statistical methods,
      machine learning tools took an important place in drug formulation. Twenty years
      ago, the first papers describing application of artificial neural networks in
      optimization of modified release products appeared. Since then, a lot of work has
      been done towards implementation of new techniques, especially Artificial Neural
      Networks (ANN) in modeling of production, drug release and drug stability of
      modified release solid dosage forms. The aim of this paper is to review
      artificial neural networks in evaluation and optimization of modified release
      solid dosage forms. 

PMID- 24300370
TI  - Development of a taste-masked orodispersible film containing dimenhydrinate.
AB  - Orodispersible dosage forms are promising new approaches for drug delivery. They
      enable an easy application, as there is no need to drink high amounts of liquids
      or swallow large solid dosage forms. The aim of the study was to develop an
      orodispersible film (ODF) as an alternative to tablets, syrups or suppositories
      for the treatment of vomiting and nausea, especially for the pediatric
      population. Formulations were investigated by X-ray diffraction, scanning
      electron and polarized light microscopy. Additionally, two commercially available
      electronic taste sensing systems were used to investigate the applied taste
      masking strategies. Results obtained from X-ray-diffraction and polarized light
      microscopy showed no recrystallization of dimenhydrinate in the formulation when
      cyclodextrin or maltodextrin were used as solubilizing and complexing agent. All
      ODFs showed fast disintegration depending on the characterization method. In
      order to get taste information, the dimenhydrinate formulations were analytically
      compared to pure drug and drug-free formulations by electronic tongues. Results
      obtained from both systems are comparable and were used together for the first
      time. It was possible to develop an ODF of dimenhydrinate that is fast
      disintegrating even in small volumes of liquid. Furthermore, in vitro taste
      assessment by two electronic tongues revealed taste-masking effects by the
      excipients. 

PMID- 24300372
TI  - Composition influence on pulmonary delivery of rifampicin liposomes.
AB  - The effects of lipid concentration and composition on the physicochemical
      properties, aerosol performance and in vitro toxicity activity of several
      rifampicin-loaded liposomes were investigated. To this purpose, six liposome
      formulations containing different amounts of soy phosphatidylcholine and
      hydrogenated soy phosphatidylcholine, with and without cholesterol and oleic
      acid, were prepared and fully characterized. Uni- or oligo-lamellar, small (~100
      nm), negatively charged (~60 mV) vesicles were obtained. Lipid composition
      affected aerosol delivery features of liposomal rifampicin; in particular, the
      highest phospholipid concentration led to a better packing of the vesicular
      bilayers with a consequent higher nebulization stability. The retention of drug
      in nebulized vesicles (NER%) was higher for oleic acid containing vesicles (55%
      +/- 1.4%) than for the other samples (~47%). A549 cells were used to evaluate
      intracellular drug uptake and in vitro toxicity activity of rifampicin-loaded
      liposomes in comparison with the free drug. Cell toxicity was more evident when
      oleic acid containing liposomes were used. 

PMID- 24300371
TI  - Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in Preclinical
      Studies of Antivascular Treatments.
AB  - Antivascular treatments can either be antiangiogenic or targeting established
      tumour vasculature. These treatments affect the tumour microvasculature and
      microenvironment but may not change clinical measures like tumour volume and
      growth. In research on antivascular treatments, information on the tumour
      vasculature is therefore essential. Preclinical research is often used for
      optimization of antivascular drugs alone or in combined treatments. Dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) is an in vivo imaging
      method providing vascular information, which has become an important tool in both
      preclinical and clinical research. This review discusses common DCE-MRI imaging
      protocols and analysis methods and provides an overview of preclinical research
      on antivascular treatments utilizing DCE-MRI. 

PMID- 24300373
TI  - Signal detection and monitoring based on longitudinal healthcare data.
AB  - Post-marketing detection and surveillance of potential safety hazards are crucial
      tasks in pharmacovigilance. To uncover such safety risks, a wide set of
      techniques has been developed for spontaneous reporting data and, more recently,
      for longitudinal data. This paper gives a broad overview of the signal detection
      process and introduces some types of data sources typically used. The most
      commonly applied signal detection algorithms are presented, covering simple
      frequentistic methods like the proportional reporting rate or the reporting odds
      ratio, more advanced Bayesian techniques for spontaneous and longitudinal data,
      e.g., the Bayesian Confidence Propagation Neural Network or the Multi-item Gamma
      Poisson Shrinker and methods developed for longitudinal data only, like the IC
      temporal pattern detection. Additionally, the problem of adjustment for
      underlying confounding is discussed and the most common strategies to
      automatically identify false-positive signals are addressed. A drug monitoring
      technique based on Wald's sequential probability ratio test is presented. For
      each method, a real-life application is given, and a wide set of literature for
      further reading is referenced. 

PMID- 24300374
TI  - SNEDDS Containing Poorly Water Soluble Cinnarizine; Development and in Vitro
      Characterization of Dispersion, Digestion and Solubilization.
AB  - Self-Nanoemulsifying Drug Delivery Systems (SNEDDSs) were developed using well
      defined excipients with the objective of mimicking digested SNEDDSs without the
      use of enzymes and in vitro lipolysis models and thereby enabling studies of the
      morphology and size of nanoemulsions as well as digested nanoemulsions by Cryo
      TEM imaging and Dynamic Light Scattering. Four SNEDDSs (I-IV) were developed.
      Going from SNEDDS I to IV lipid content and solubility of the model drug
      cinnarizine decreased, which was also the case for dispersion time and droplet
      size. Droplet size of all SNEDDS was evaluated at 1% (w/w) dispersion under
      different conditions. Cinnarizine incorporation increased the droplet size of
      SNEDDSs I and II whereas for SNEDDSs III and IV no difference was observed. At
      low pH cinnarizine had no effect on droplet size, probably due to increased
      aqueous solubility and partitioning into the aqueous phase. Dispersion of the
      SNEDDSs in Simulated Intestinal Media (SIM) containing bile salts and
      phospholipids resulted in a decrease in droplet size for all SNEDDS, as compared
      to dispersion in buffer. Increasing the bile salt/phospholipid content in the SIM
      decreased the droplet sizes further. Mimicked digested SNEDDS with highest lipid
      content (I and II) formed smaller nanoemulsion droplet sizes upon dispersion in
      SIM, whereas droplet size from III and IV were virtually unchanged by digestion.
      Increasing the bile acid/phosphatidylcholine content in the SIM generally
      decreased droplet size, due to the solubilizing power of the endogenous
      surfactants. Digestion of SNEDDSs II resulted in formation of vesicles or
      micelles in fasted and fed state SIM, respectively. The developed and
      characterized SNEDDS provide for a better knowledge of the colloid phases
      generated during digestion of SNEDDS and therefore will enable studies that may
      yield a more detailed understanding of SNEDDS performance. 

PMID- 24300376
TI  - Formaldoxime hydrogen bonded complexes with ammonia and hydrogen chloride.
AB  - An infrared spectroscopic and MP2/6-311++G(2d,2p) study of hydrogen bonded
      complexes of formaldoxime with ammonia and hydrogen chloride trapped in solid
      argon matrices is reported. Both 1:1 and 1:2 complexes between formaldoxime and
      ammonia, hydrogen chloride have been identified in the CH2NOH/NH3/Ar,
      CH2NOH/HCl/Ar matrices, respectively, their structures were determined by
      comparison of the spectra with the results of calculations. In the 1:1 complexes
      present in the argon matrices the OH group of formaldoxime acts as a proton donor
      for ammonia and the nitrogen atom acts as a proton acceptor for hydrogen
      chloride. In the 1:2 complexes ammonia or hydrogen chloride dimers interact both
      with the OH group and the nitrogen atom of CH2NOH to form seven membered cyclic
      structures stabilized by three hydrogen bonds. The theoretical spectra generally
      agree well with the experimental ones, but they seriously underestimate the shift
      of the OH stretch for the 1:1 CH2NOH?NH3 complex. 

PMID- 24300375
TI  - Autophagy and SQSTM1 on the RHOA(d) again: emerging roles of autophagy in the
      degradation of signaling proteins.
AB  - Degradation of signaling proteins is one of the most powerful tumor-suppressive
      mechanisms by which a cell can control its own growth, its survival, and its
      motility. Emerging evidence suggests that autophagy limits several signaling
      pathways by degrading kinases, downstream components, and transcription factors;
      however, this often occurs under stressful conditions. Our recent studies
      revealed that constitutive autophagy temporally and spatially controls the RHOA
      pathway. Specifically, inhibition of autophagosome degradation induces the
      accumulation of the GTP-bound form of RHOA. The active RHOA is sequestered via
      SQSTM1/p62 within autolysosomes, and accordingly fails to localize to the spindle
      midbody or to the cell surface, as we demonstrate herein. As a result, all RHOA
      downstream responses are deregulated, thus driving cytokinesis failure,
      aneuploidy and motility, three processes that directly have an impact upon cancer
      progression. We therefore propose that autophagy acts as a degradative brake for
      RHOA signaling and thereby controls cell proliferation, migration, and genome
      stability. 

PMID- 24300378
TI  - Comparison of gamma (Anger) camera systems in terms of detective quantum
      efficiency using Monte Carlo simulation.
AB  - AIM: The aim of the present study was to perform an extensive evaluation of
      available gamma camera systems in terms of their detective quantum efficiency
      (DQE) and determine their dependency on relevant parameters such as collimator
      type, imaging depth, and energy window using the Monte Carlo technique. MATERIALS
      AND METHODS: The modulation transfer function was determined from a simulated
      (99m)Tc point source and was combined with the system sensitivity and photon
      yield to obtain the DQE of the system. The simulations were performed for
      different imaging depths in a water phantom for 13 gamma camera systems from four
      manufacturers. RESULTS: Except at very low spatial frequencies, the highest DQE
      values were found with a lower energy window threshold of around 130 keV for all
      systems. The height and shape of the DQE curves were affected by the collimator
      design and the intrinsic properties of the gamma camera systems. High-sensitivity
      collimators gave the highest DQE at low spatial frequencies, whereas the high
      resolution and ultrahigh-resolution collimators showed higher DQE values at
      higher frequencies. The intrinsic resolution of the system mainly affected the
      DQE curve at superficial depths. CONCLUSION: The results indicate that the
      manufacturers have succeeded differently in their attempts to design a system
      constituting an optimal compromise between sensitivity and spatial resolution.

PMID- 24300377
TI  - Microarray-based identification of individual HERV loci expression: application
      to biomarker discovery in prostate cancer.
AB  - The prostate-specific antigen (PSA) is the main diagnostic biomarker for prostate
      cancer in clinical use, but it lacks specificity and sensitivity, particularly in
      low dosage values(1). 'How to use PSA' remains a current issue, either for
      diagnosis as a gray zone corresponding to a concentration in serum of 2.5-10
      ng/ml which does not allow a clear differentiation to be made between cancer and
      noncancer(2) or for patient follow-up as analysis of post-operative PSA kinetic
      parameters can pose considerable challenges for their practical application(3,4).
      Alternatively, noncoding RNAs (ncRNAs) are emerging as key molecules in human
      cancer, with the potential to serve as novel markers of disease, e.g. PCA3 in
      prostate cancer(5,6) and to reveal uncharacterized aspects of tumor biology.
      Moreover, data from the ENCODE project published in 2012 showed that different
      RNA types cover about 62% of the genome. It also appears that the amount of
      transcriptional regulatory motifs is at least 4.5x higher than the one
      corresponding to protein-coding exons. Thus, long terminal repeats (LTRs) of
      human endogenous retroviruses (HERVs) constitute a wide range of
      putative/candidate transcriptional regulatory sequences, as it is their primary
      function in infectious retroviruses. HERVs, which are spread throughout the human
      genome, originate from ancestral and independent infections within the germ line,
      followed by copy-paste propagation processes and leading to multicopy families
      occupying 8% of the human genome (note that exons span 2% of our genome). Some
      HERV loci still express proteins that have been associated with several
      pathologies including cancer(7-10). We have designed a high-density microarray,
      in Affymetrix format, aiming to optimally characterize individual HERV loci
      expression, in order to better understand whether they can be active, if they
      drive ncRNA transcription or modulate coding gene expression. This tool has been
      applied in the prostate cancer field (Figure 1). 

PMID- 24300379
TI  - Evaluation of soft-tissue lesions with (18)F-FDG PET/CT: initial results of a
      prospective trial.
AB  - PURPOSE OF THE REPORT: Although MRI is utilized for planning the resection of
      soft-tissue tumors, it is not always capable of differentiating benign from
      malignant lesions. The risk of local recurrence of soft-tissue sarcomas is
      increased when biopsies are performed before resection and by inadequate
      resections. PET associated with computed tomography using fluorodeoxyglucose
      labeled with fluorine-18 ((18)F-FDG PET/CT) may help differentiate between benign
      and malignant tumors, thus avoiding inadequate resections and making prior
      biopsies unnecessary. The purpose of this study was to evaluate the usefulness of
      (18)F-FDG PET/CT in differentiating benign from malignant solid soft-tissue
      lesions. MATERIALS AND METHODS: Patients with solid lesions of the limbs or
      abdominal wall detected by MRI were submitted to (18)F-FDG PET/CT. The maximum
      standardized uptake value (SUVmax) cutoff was determined to differentiate
      malignant from benign tumors. Regardless of the (18)F-FDG PET/CT results all
      patients underwent biopsy and surgery. RESULTS: MRI was performed in 54 patients,
      and 10 patients were excluded because of purely lipomatose or cystic lesions.
      (18)F-FDG PET/CT was performed in the remaining 44 patients. Histopathology
      revealed 26 (59%) benign and 18 (41%) malignant soft-tissue lesions. A
      significant difference in SUVmax was observed between benign and malignant soft
      tissue lesions. The SUVmax cutoff of 3.0 differentiated malignant from benign
      lesions with 100% sensitivity, 83.3% specificity, 89.6% accuracy, 78.3% positive
      predictive value, and 100% negative predictive value. CONCLUSION: (18)F-FDG
      PET/CT seems to be able to differentiate benign from malignant soft-tissue
      lesions with good accuracy and very high negative predictive value. Incorporating
      (18)F-FDG PET/CT into the diagnostic algorithm of these patients may prevent
      inadequate resections and unnecessary biopsies.

PMID- 24300380
TI  - How to assess background activity: introducing a histogram-based analysis as a
      first step for accurate one-step PET quantification.
AB  - Many common PET segmentation methods for malignant lesions use surrounding
      background activity as a reference. To date, background has to be measured by
      drawing a second volume of interest (VOI) in nearby, undiseased tissue. This is
      time consuming as two VOIs have to be determined for each lesion. The aim of our
      study was to analyse whether background activity in different organs and body
      regions could be calculated from the tumour VOI by histogram analyses. The
      institutional review board waived informed consent for this retrospective study.
      For each of the following tumour types and areas - head and neck (neck), lung,
      hepatic metastasis (liver), melanoma (skin), and cervix (pelvis) - 10 consecutive
      patients with biopsy-proven tumours who underwent (18)F-fluorodeoxyglucose-PET in
      January 2012 were retrospectively selected. One lesion was selected and two
      readers drew a cubical VOI around the lesion (VOItumour) and over the background
      (VOIBG). The mean value of VOIBG was compared with the mode of the histogram,
      using equivalence testing with an equivalence margin of +/-0.5 SUV. Inter-reader
      agreement was analysed for the mean background, and the mode of the VOItumour
      histogram was assessed using the concordance correlation coefficient. For both
      readers, the mode of VOItumour was equivalent to the mean of VOIBG (P<0.0001 for
      R1 and R2). The inter-reader agreement was almost perfect, with a concordance
      correlation coefficient of greater than 0.92 for both the mode of VOItumour and
      the mean of VOIBG. Background activity determined within a tumour VOI using
      histogram analysis is equivalent to separately measured mean background values,
      with an almost perfect inter-reader agreement. This could facilitate PET
      quantification methods based on background values without increasing workload.

PMID- 24300381
TI  - [Potential selection bias in telephone surveys: landline and mobile phones].
AB  - The increasing use of mobile phones in the last decade has decreased landline
      telephone coverage in Spanish households. This study aimed to analyze
      sociodemographic characteristics and health indicators by type of telephone
      service (mobile phone vs. landline or landline and mobile phone). Two telephone
      surveys were conducted in Spanish samples (February 2010 and February 2011).
      Multivariate logistic regression analyses were performed to analyze differences
      in the main sociodemographic characteristics and health indicators according to
      the type of telephone service available in Spanish households. We obtained 2027
      valid responses (1627 landline telephones and 400 mobile phones). Persons
      contacted through a mobile phone were more likely to be a foreigner, to belong to
      the manual social class, to have a lower educational level, and to be a smoker
      than those contacted through a landline telephone. The profile of the population
      that has only a mobile phone differs from that with a landline telephone.
      Therefore, telephone surveys that exclude mobile phones could show a selection
      bias. 

PMID- 24300382
TI  - [Does gender really affect the socio-economic characteristics of the primary
      caregiver in Alzheimer's disease?].

PMID- 24300383
TI  - [Mercury concentrations in women's hair in a native community of Peru].

PMID- 24300384
TI  - Expression of functional recombinant hemagglutinin and neuraminidase proteins
      from the novel H7N9 influenza virus using the baculovirus expression system.
AB  - The baculovirus expression system is a powerful tool for expression of
      recombinant proteins. Here we use it to produce correctly folded and glycosylated
      versions of the influenza A virus surface glycoproteins - the hemagglutinin (HA)
      and the neuraminidase (NA). As an example, we chose the HA and NA proteins
      expressed by the novel H7N9 virus that recently emerged in China. However the
      protocol can be easily adapted for HA and NA proteins expressed by any other
      influenza A and B virus strains. Recombinant HA (rHA) and NA (rNA) proteins are
      important reagents for immunological assays such as ELISPOT and ELISA, and are
      also in wide use for vaccine standardization, antibody discovery, isolation and
      characterization. Furthermore, recombinant NA molecules can be used to screen for
      small molecule inhibitors and are useful for characterization of the enzymatic
      function of the NA, as well as its sensitivity to antivirals. Recombinant HA
      proteins are also being tested as experimental vaccines in animal models, and a
      vaccine based on recombinant HA was recently licensed by the FDA for use in
      humans. The method we describe here to produce these molecules is straight
      forward and can facilitate research in influenza laboratories, since it allows
      for production of large amounts of proteins fast and at a low cost. Although here
      we focus on influenza virus surface glycoproteins, this method can also be used
      to produce other viral and cellular surface proteins. 

PMID- 24300385
TI  - Enhanced splice correction by 3', 5'-serinol and 2'-(omega-O-methylserinol)
      guarded OMe-RNA/DNA mixmers in cells.
AB  - Development of artificial nucleic acids for therapeutic applications warrants
      that the oligomers be endowed with high specificity, enzymatic stability and with
      no/reduced off-target effects. The balance between strength of the duplex with
      target RNA and enzyme stability is therefore the key factor for the designed
      modification. The chiral serinol derivative combines the attributes of amino- and
      methoxy- substitution when at 2'- position and at 3'- and 5'- ends, effectively
      balancing the duplex stability and resistance to hydrolytic enzymes. The
      biological effect seen is the remarkable improvement in splice correction by the
      steric blocking antisense oligonucleotide with just 4 modified units, i.e ~20%
      substitution with R-aminomethoxypropyloxy (R-AMP)-thymidine within the 2'-OMe
      18mer sequence.

PMID- 24300386
TI  - Views of pregnant women in South Western Sydney towards dental care and an oral
      health program initiated by midwives.
AB  - ISSUES ADDRESSED: Oral health during pregnancy is important, yet is often
      neglected by women. A program is currently being developed for midwives in
      Australia to promote maternal oral health. The aim of this study was to record
      the views of pregnant women in Australia towards dental care and midwives
      promoting oral health. METHODS: Using convenience sampling, a cross-sectional
      survey was undertaken of 241 pregnant women attending a metropolitan hospital in
      South Western Sydney in 2010. RESULTS: Only 10% of women received oral-health
      promotional material during pregnancy. More than 50% reported dental problems,
      yet only 17% had discussed this with their midwives and less than half (44.6%)
      had sought dental treatment. The main barriers to obtaining dental care were:
      lack of awareness, safety concerns about dental treatment and dental costs.
      Pregnant women were more likely (P<0.05) to see a dentist if they had received
      information about oral health (odds ratio (OR) 3.25, 95% CI 1.34-7.90) and had
      private health insurance (OR 2.47, 95% CI 1.26-4.85). Most women (>90%) were
      receptive to midwives providing oral-health education, assessments and referrals
      to affordable dental services. CONCLUSION: This study has shown that pregnant
      women are receiving limited dental advice and are concerned about dental costs.
      It has also confirmed for the first time in Australia that women are very
      positive about receiving oral-health advice from midwives during their pregnancy.
      SO WHAT?: Oral-health promotion programs during pregnancy should consider using
      midwives to increase dental awareness among women and provide pathways to
      affordable dental services.

PMID- 24300387
TI  - Cardiac output monitoring in obstetric anaesthesia.

PMID- 24300388
TI  - Intra-aortic balloon occlusion without fluoroscopy for severe postpartum
      haemorrhage secondary to placenta percreta.

PMID- 24300390
TI  - Syntheses of diacyltanshinol derivatives and their suppressive effects on
      macrophage foam cell formation by reducing oxidized LDL uptake.
AB  - A series of diacyltanshinol derivatives were synthesized by esterifying the
      corresponding o-hydroquinones of tanshinones. The suppressive effects of the
      synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and
      oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results
      indicated that the nicotinate derivatives 1a and 2a, modified from tanshinone IIA
      and cryptotanshinone, showed stronger suppressive activity on oxLDL uptake and
      the resultant foam cell formation relative to tanshinone IIA. Western Blot
      analysis indicated that derivatives 1a and 2a could dose-dependently inhibit the
      expression of oxLDL-induced LOX-1, implying that the suppressive effects of 1a
      and 2a on oxLDL uptake and foam cell formation could be at least partially
      attributed to the inhibition of LOX-1 expression in macrophages.

PMID- 24300391
TI  - Screening and verification of ssDNA aptamers targeting human hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world.
      Molecular probes that can recognize biomarkers specific for HCC are urgently
      needed to improve the sensitivity and specificity of early diagnosis. A recent
      study has applied the method of systematic evolution of ligands by exponential
      enrichment and produced several aptamers that can bind specifically to mouse
      liver cancer cells and tissues. However, the binding affinity to human liver
      cancer has not been fully identified. Using human-derived hepatoma cell line
      HepG2 as positive target cell line and normal hepatocyte cell line HL-7702 as
      negative one, we obtained an aptamer HA09 that could specifically bind to human
      liver cancer cells with Kd in the nanomolar range and recognize paraffin-embedded
      human HCC tissues. This aptamer may facilitate the discovery of novel biomarkers
      and serve as an ideal molecular probe for intracellular delivery with both
      diagnostic and therapeutic implications.

PMID- 24300392
TI  - Comparison of high-sensitivity C-reactive protein level between systemic and
      coronary circulation in patients with acute myocardial infarction.

PMID- 24300389
TI  - Intracellular calcium channels: inositol-1,4,5-trisphosphate receptors.
AB  - The inositol-1,4,5-trisphosphate receptors (InsP3Rs) are the major intracellular
      Ca(2+)-release channels in cells. Activity of InsP3Rs is essential for elementary
      and global Ca(2+) events in the cell. There are three InsP3Rs isoforms that are
      present in mammalian cells. In this review we will focus primarily on InsP3R type
      1. The InsP3R1 is a predominant isoform in neurons and it is the most extensively
      studied isoform. Combination of biophysical and structural methods revealed key
      mechanisms of InsP3R function and modulation. Cell biological and biochemical
      studies lead to identification of a large number of InsP3R-binding proteins.
      InsP3Rs are involved in the regulation of numerous physiological processes,
      including learning and memory, proliferation, differentiation, development and
      cell death. Malfunction of InsP3R1 play a role in a number of neurodegenerative
      disorders and other disease states. InsP3Rs represent a potentially valuable drug
      target for treatment of these disorders and for modulating activity of neurons
      and other cells. Future studies will provide better understanding of
      physiological functions of InsP3Rs in health and disease. 

PMID- 24300393
TI  - Stress response in Pectobacterium atrosepticum SCRI1043 under starvation
      conditions: adaptive reactions at a low population density.
AB  - The adaptive reactions of plant pathogenic bacterium Pectobacterium atrosepticum
      SCRI1043 under starvation conditions were studied. The main emphasis was given to
      the peculiarities of stress responses depending on the bacterial population
      densities. When bacteria were subjected to starvation at high population
      densities (10(7)-10(9) CFU ml(-1)), their adaptive reactions conformed to the
      conventional conception of bacterial adaptation related to autolysis of part of
      the population, specific modification of cell ultrastructure, activation of
      expression of stress responsive genes and acquiring cross protection against
      other stress factors. In contrast, at low initial population densities (10(3)
      10(5) CFU ml(-1)), as described in our recent work, the cell density increased
      due to multiple cell division despite the absence of exogenous growth substrate.
      Here we present data that demonstrate that such unconventional behavior is part
      of a stress response, which provides increased stress tolerance while retaining
      virulence. Cell morphology and gene expression in high- and low-cell-density
      starving Pba cultures were compared. Our investigation demonstrates the existence
      of alternative adaptive strategies enabling pathogenic bacteria to cope with a
      variety of stress factors, including starvation, especially necessary when
      residing outside of their host. 

PMID- 24300394
TI  - Efavirenz dissolution enhancement I: co-micronization.
AB  - AIDS constitutes one of the most serious infectious diseases, representing a
      major public health priority. Efavirenz (EFV), one of the most widely used drugs
      for this pathology, belongs to the Class II of the Biopharmaceutics
      Classification System for drugs with very poor water solubility. To improve EFV's
      dissolution profile, changes can be made to the physical properties of the drug
      that do not lead to any accompanying molecular modifications. Therefore, the
      study objective was to develop and characterize systems with efavirenz able to
      improve its dissolution, which were co-processed with sodium lauryl sulfate (SLS)
      and polyvinylpyrrolidone (PVP). The technique used was co-micronization. Three
      different drug:excipient ratios were tested for each of the two carriers. The
      drug dispersion dissolution results showed significant improvement for all the co
      processed samples in comparison to non-processed material and corresponding
      physical mixtures. The dissolution profiles obtained for dispersion with co
      micronized SLS samples proved superior to those of co-micronized PVP, with the
      proportion (1:0.25) proving the optimal mixture. The improvements may be
      explained by the hypothesis that formation of a hydrophilic layer on the surface
      of the micronized drug increases the wettability of the system formed,
      corroborated by characterization results indicating no loss of crystallinity and
      an absence of interaction at the molecular level. 

PMID- 24300395
TI  - Organic nitrate maintains bone marrow blood perfusion in ovariectomized female
      rats: a dynamic, contrast-enhanced magnetic resonance imaging (MRI) study.
AB  - This study investigated the effects of nitrate on bone mineral density (BMD) and
      bone marrow perfusion in ovariectomized (OVX) female rats, and also the effects
      of nitrate on in vitro osteoblastic activity and osteoclastic differentiation of
      murine monocyte/ macrophage RAW 264.7 cells. Female Sprague-Dawley rats were
      divided into OVX + nitrate group (isosorbide-5-mononitrate, ISM, 150 mg/kg/ day
      b.i.d), OVX + vehicle group, and control group. Lumbar spine CT bone densitometry
      and perfusion MRI were performed on the rats at baseline and week 8 post-OVX. The
      OVX rats' BMD decreased by 22.5% +/- 5.7% at week 8 (p < 0.001); while the OVX +
      ISM rats' BMD decreased by 13.1% +/- 2.7% (p < 0.001). The BMD loss difference
      between the two groups of rats was significant (p = 0.018). The OVX rats' lumbar
      vertebral perfusion MRI maximum enhancement (Emax) decreased by 10.3% +/- 5.0% at
      week 8 (p < 0.005), while in OVX + ISM rats, the Emax increased by 5.5% +/- 6.9%
      (p > 0.05). The proliferation of osteoblast-like UMR-106 cells increased
      significantly with ISM treatment at 0.78 uM to 50 MUM. Treatment of UMR-106 cells
      with ISM also stimulated the BrdU uptake. After the RAW 264.7 cells were co
      treated with osteoclastogenesis inducer RANKL and 6.25 MUM ~ 100 MUM of ISM for 3
      days, a trend of dose-dependent increase of osteoclast number was noted. 

PMID- 24300397
TI  - Correlating physicochemical properties of boronic Acid-chitosan conjugates to
      glucose adsorption sensitivity.
AB  - Phenyl boronic acid (PBA), which is known to interact with glucose, was
      covalently bonded to chitosan by direct reductive N-alkylation of chitosan with 4
      formylphenylboronic acid (4-FPBA). Evidence of PBA bonding on chitosan was
      assessed by FTIR, ToF-SIMS, SEM, DSC and glucose adsorption sensitivity
      measurements. FTIR spectra showed strong signals at 1560 and 630 cm-1 indicating
      the formation of p-substituted benzene. Similarly, ToF-SIMS analyses on the
      conjugates registered fragments of boron ion (B-) at 11.0 m/z whose intensity
      increased in proportion to 4-FPBA loading. The degree to which PBA was bonded to
      chitosan was related to the 4-FPBA load used in the reaction (termed F1 through
      to F6 with increasing 4-FPBA load). Glucose adsorption sensitivity to PBA-bonded
      chitosan was directly related to the amount of PBA functionality within the
      conjugates and the physical nature of the matrices (porous or crystalline).
      Topographic analysis by SEM revealed that PBA-chitosan conjugates F1, F2 and F3
      have porous matrices and their sensitivity to glucose adsorption was directly
      proportional to the degree of PBA substitution onto chitosan. Conversely,
      conjugates F4, F5 and F6 appeared crystalline under SEM and glucose adsorption
      sensitivity decreased in proportion to amount of PBA bonded to chitosan. The
      crystalline nature of the conjugates was confirmed by DSC, where the exothermic
      event related to the melting of the bonded PBA moiety, occurred at 338  degrees
      C. Thus, decreased sensitivity to glucose adsorption by the conjugates can be
      ascribed to the crystallinity imparted by increased content of the bonded PBA
      moiety, providing an optimal loading of PBA in terms of maximizing response to
      glucose. 

PMID- 24300396
TI  - Protein Adsorption Patterns and Analysis on IV Nanoemulsions-The Key Factor
      Determining the Organ Distribution.
AB  - Intravenous nanoemulsions have been on the market for parenteral nutrition since
      the 1950s; meanwhile, they have also been used successfully for IV drug delivery.
      To be well tolerable, the emulsions should avoid uptake by the MPS cells of the
      body; for drug delivery, they should be target-specific. The organ distribution
      is determined by the proteins adsorbing them after injection from the blood
      (protein adsorption pattern), typically analyzed by two-dimensional
      polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE
      method, the analytical problems to be faced and the knowledge available on how
      the composition of emulsions affects the protein adsorption patterns, e.g., the
      composition of the oil phase, stabilizer layer and drug incorporation into the
      interface or oil core. Data were re-evaluated and compared, and the implications
      for the in vivo distribution are discussed. Major results are that the
      interfacial composition of the stabilizer layer is the main determining factor
      and that this composition can be modulated by simple processes. Drug
      incorporation affects the pattern depending on the localization of the drug (oil
      core versus interface). The data situation regarding in vivo effects is very
      limited; mainly, it has to be referred to in the in vivo data of polymeric
      nanoparticles. As a conclusion, determination of the protein adsorption patterns
      can accelerate IV nanoemulsion formulation development regarding optimized organ
      distribution and related pharmacokinetics. 

PMID- 24300398
TI  - Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of
      Ridaforolimus in Rat.
AB  - The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative
      effects in cancer treatment, and it currently is being evaluated in a range of
      clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with
      limited aqueous solubility, which may benefit from formulation with polymeric
      micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl
      sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE
      PEG2000) via a solvent extraction technique. Micelle loading greatly improved the
      solubility of ridaforolimus by approximately 40 times from 200 MUg/mL to 8.9
      mg/mL. The diameters of the drug-loaded micelles were 33 +/- 15 nm indicating
      they are of appropriate size to accumulate within the tumor site via the enhanced
      permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was
      dosed intravenously to rats at 10 mg/kg and compared to a control of
      ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half
      life of ridaforolimus by 170% and decreased the clearance by 58%, which is
      consistent with improved retention of the drug in the plasma by the micelle
      formulation. 

PMID- 24300399
TI  - Safety monitoring in clinical trials.
AB  - Monitoring patient safety during clinical trials is a critical component
      throughout the drug development life-cycle. Pharmaceutical sponsors must work
      proactively and collaboratively with all stakeholders to ensure a systematic
      approach to safety monitoring. The regulatory landscape has evolved with
      increased requirements for risk management plans, risk evaluation and
      minimization strategies. As the industry transitions from passive to active
      safety surveillance activities, there will be greater demand for more
      comprehensive and innovative approaches that apply quantitative methods to
      accumulating data from all sources, ranging from the discovery and preclinical
      through clinical and post-approval stages. Statistical methods, especially those
      based on the Bayesian framework, are important tools to help provide objectivity
      and rigor to the safety monitoring process. 

PMID- 24300400
TI  - Steroid nanocrystals prepared using the nano spray dryer B-90.
AB  - The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the
      production of drug nanocrystals. In this study, the preparation of steroid
      nanocrystals using the Nano Spray Dryer B-90 was demonstrated. The particle size
      was controlled by selecting the mesh aperture size. Submicrometer steroid
      particles in powder form were successfully obtained. These nanoparticles were
      confirmed to have a crystal structure using powder X-ray diffraction pattern
      analysis. Since drug nanocrystals have recently been considered as a novel type
      of drug formulation for drug delivery systems, this study will be useful for nano
      medical applications. 

PMID- 24300401
TI  - Analytical electron microscopy for characterization of fluid or semi-solid
      multiphase systems containing nanoparticulate material.
AB  - The analysis of nanomaterials in pharmaceutical or cosmetic preparations is an
      important aspect both in formulation development and quality control of marketed
      products. Despite the increased popularity of nanoparticulate compounds
      especially in dermal preparations such as emulsions, methods and protocols of
      analysis for the characterization of such systems are scarce. This work combines
      an original sample preparation procedure along with different methods of
      analytical electron microscopy for the comprehensive analysis of fluid or semi
      solid dermal preparations containing nanoparticulate material. Energy-filtered
      transmission electron microscopy, energy-dispersive X-ray spectroscopy, electron
      energy loss spectroscopy and high resolution imaging were performed on model
      emulsions and a marketed product to reveal different structural aspects of both
      the emulsion bulk phase and incorporated nanosized material. An innovative
      analytical approach for the determination of the physical stability of the
      emulsion under investigation is presented. Advantages and limitations of the
      employed analytical imaging techniques are highlighted. 

PMID- 24300403
TI  - Vaccine Safety Surveillance Systems: Critical Elements and Lessons Learned in the
      Development of the US Vaccine Safety Datalink's Rapid Cycle Analysis
      Capabilities.
AB  - Since the late 1990s, there have been tremendous strides made in improving the
      capacity for carrying out routine active surveillance of new vaccines in the
      United States. These strides have led to new surveillance systems that are now in
      place. Some of the critical elements that are part of successful vaccine or drug
      safety surveillance systems include their use of (i) longitudinal data from a
      discrete enumerated population base, (ii) frequent, routine transfers of small
      amounts of data that are easy to collect and collate, (iii) avoidance of mission
      creep, (iv) statistical capabilities, (v) creation of an "industrialized process"
      approach and (vi) political safe harbor. 

PMID- 24300404
TI  - Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker
      and Comparison to the Tree-based Scan Statistic.
AB  - BACKGROUND: Drug adverse event (AE) signal detection using the Gamma Poisson
      Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection
      using large observational health plan databases can expand medication safety
      surveillance. METHODS: Using data from nine health plans, we conducted a pilot
      study to evaluate the implementation and findings of the GPS approach for two
      antifungal drugs, terbinafine and itraconazole, and two diabetes drugs,
      pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into
      183 different clinical concepts and four levels of granularity. Several signaling
      thresholds were assessed. GPS results were compared to findings from a companion
      study using the identical analytic dataset but an alternative statistical method
      the tree-based scan statistic (TreeScan). RESULTS: We identified 71 statistical
      signals across two signaling thresholds and two methods, including closely
      related signals of overlapping diagnosis definitions. Initial review found that
      most signals represented known adverse drug reactions or confounding. About 31%
      of signals met the highest signaling threshold. CONCLUSIONS: The GPS method was
      successfully applied to observational health plan data in a distributed data
      environment as a drug safety data mining method. There was substantial
      concordance between the GPS and TreeScan approaches. Key method implementation
      decisions relate to defining exposures and outcomes and informed choice of
      signaling thresholds.

PMID- 24300405
TI  - Exploring polymeric micelles for improved delivery of anticancer agents: recent
      developments in preclinical studies.
AB  - As versatile drug delivery systems, polymeric micelles have demonstrated
      particular strength in solubilizing hydrophobic anticancer drugs while
      eliminating the use of toxic organic solvents and surfactants. However, the true
      promise of polymeric micelles as drug carriers for cancer therapy resides in
      their potential ability to preferentially elevate drug exposure in the tumor and
      achieve enhanced anticancer efficacy, which still remains to be fully exploited.
      Here, we review various micellar constructs that exhibit the enhanced permeation
      and retention effect in the tumor, the targeting ligands that potentiate the
      anticancer efficacy of micellar drugs, and the polyplex micelle systems suitable
      for the delivery of plasmid DNA and small interference RNA. Together, these
      preclinical studies in animal models help us further explore polymeric micelles
      as emerging drug carriers for targeted cancer therapy. 

PMID- 24300406
TI  - Biochemical titration of glycogen in vitro.
AB  - Glycogen is the main energetic polymer of glucose in vertebrate animals and plays
      a crucial role in whole body metabolism as well as in cellular metabolism. Many
      methods to detect glycogen already exist but only a few are quantitative. We
      describe here a method using the Abcam Glycogen assay kit, which is based on
      specific degradation of glycogen to glucose by glucoamylase. Glucose is then
      specifically oxidized to a product that reacts with the OxiRed probe to produce
      fluorescence. Titration is accurate, sensitive and can be achieved on cell
      extracts or tissue sections. However, in contrast to other techniques, it does
      not give information about the distribution of glycogen in the cell. As an
      example of this technique, we describe here the titration of glycogen in two cell
      lines, Chinese hamster lung fibroblast CCL39 and human colon carcinoma LS174,
      incubated in normoxia (21% O2) versus hypoxia (1% O2). We hypothesized that
      hypoxia is a signal that prepares cells to synthesize and store glycogen in order
      to survive(1). 

PMID- 24300402
TI  - From molecular to nanotechnology strategies for delivery of neurotrophins:
      emphasis on brain-derived neurotrophic factor (BDNF).
AB  - Neurodegenerative diseases represent a major public health problem, but
      beneficial clinical treatment with neurotrophic factors has not been established
      yet. The therapeutic use of neurotrophins has been restrained by their
      instability and rapid degradation in biological medium. A variety of strategies
      has been proposed for the administration of these leading therapeutic candidates,
      which are essential for the development, survival and function of human neurons.
      In this review, we describe the existing approaches for delivery of brain-derived
      neurotrophic factor (BDNF), which is the most abundant neurotrophin in the
      mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged
      as a promising therapy against neurodegenerative disorders. Polymer-based
      carriers have provided sustained neurotrophin delivery, whereas lipid-based
      particles have contributed also to potentiation of the BDNF action.
      Nanotechnology offers new possibilities for the design of vehicles for
      neuroprotection and neuroregeneration. Recent developments in nanoscale carriers
      for encapsulation and transport of BDNF are highlighted. 

PMID- 24300413
TI  - Organelle transport in cultured Drosophila cells: S2 cell line and primary
      neurons.
AB  - Drosophila S2 cells plated on a coverslip in the presence of any actin
      depolymerizing drug form long unbranched processes filled with uniformly
      polarized microtubules. Organelles move along these processes by microtubule
      motors. Easy maintenance, high sensitivity to RNAi-mediated protein knock-down
      and efficient procedure for creating stable cell lines make Drosophila S2 cells
      an ideal model system to study cargo transport by live imaging. The results
      obtained with S2 cells can be further applied to a more physiologically relevant
      system: axonal transport in primary neurons cultured from dissociated Drosophila
      embryos. Cultured neurons grow long neurites filled with bundled microtubules,
      very similar to S2 processes. Like in S2 cells, organelles in cultured neurons
      can be visualized by either organelle-specific fluorescent dyes or by using
      fluorescent organelle markers encoded by DNA injected into early embryos or
      expressed in transgenic flies. Therefore, organelle transport can be easily
      recorded in neurons cultured on glass coverslips using living imaging. Here we
      describe procedures for culturing and visualizing cargo transport in Drosophila
      S2 cells and primary neurons. We believe that these protocols make both systems
      accessible for labs studying cargo transport. 

PMID- 24300414
TI  - Durability of efficacy after telbivudine off-treatment in chronic hepatitis B
      patients.
AB  - BACKGROUND/AIMS: Current international guidelines indicate that finite therapy
      with nucleos(t)ide analogues (NAs) is possible in chronic hepatitis B (CHB)
      patients. Here we evaluate the durability of efficacy after telbivudine (LdT) off
      treatment. METHODS: 39 CHB patients with normalized ALT, undetectable HBV-DNA and
      HBeAg seroconversion for at least 48 weeks were observed after telbivudine
      discontinuation. We analyzed the follow-up clinical condition of off-treatment,
      calculated the cumulative clinical relapse rate, and explored the predictive
      factors for clinical relapse. RESULTS: Totally 8 patients encountered clinical
      relapse in the first 60 weeks after telbivudine discontinuation. The cumulative
      clinical relapse rates at week 24, 48, 60 and 204 were respectively 2.6%, 7.7%,
      16.3% and 23.3%. No significant difference was found between cumulative clinical
      relapse rates of HBeAg(+) and HBeAg(-). No significant baseline or on-treatment
      factors for clinical relapse were found. CONCLUSION: The present study
      demonstrated that most CHB patients maintained sustained response and HBeAg
      seroconversion following telbivudine off-treatment. Clinical relapses may often
      occur in the early period, with low clinical relapse rate. More follow-up data
      will be on-going and complemented in the further studies.

PMID- 24300416
TI  - Adult asthma biomarkers.
AB  - PURPOSE OF REVIEW: A variety of novel asthma treatments have been developed based
      on phenotypes, and the clinical trial results show promising responses. This
      review summarizes the current knowledge of biomarkers for the determination of
      asthma phenotypes. RECENT FINDINGS: Eosinophilic inflammation is the most focused
      phenotype because most novel asthma treatments have targeted T-helper type 2
      (Th2) pathway. Fractional-exhaled nitric oxide (FeNO) is a new method that
      represents an eosinophilic airway inflammation with a significant correlation
      with sputum eosinophilia and asthma severity instead of sputum eosinophil count
      that easily influenced by corticosteroid therapy. However, some reports indicated
      the discordance between treatment response or adjustment and FeNO levels. Serum
      periostin is a strong serum biomarker for eosinophilic airway inflammation and an
      indicator of Th2-targeted therapy (such as lebrikizumab or omalizumab) and
      airflow limitation. YKL-40 is associated with asthma severity and airway
      remodeling. In addition, genetic and metabolomic approaches have been made to
      determine asthma phenotypes and severity. SUMMARY: Biomarkers such as FeNO and
      serum periostin represent eosinophilic airway inflammation, together with
      eosinophil-derived neurotoxin and osteopontin (OPN) needed more replication
      studies. Periostin, YKL-40, OPN and some metabolites (choline, arginine, acetone
      and protectin D1) are related to asthma severity and airflow limitation.

PMID- 24300415
TI  - Functional interrogation of adult hypothalamic neurogenesis with focal
      radiological inhibition.
AB  - The functional characterization of adult-born neurons remains a significant
      challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery
      or transgenic animals have potential confounds that make interpretation of
      results from these studies difficult. New radiological tools are emerging,
      however, that allow one to noninvasively investigate the function of select
      groups of adult-born neurons through accurate and precise anatomical targeting in
      small animals. Focal ionizing radiation inhibits the birth and differentiation of
      new neurons, and allows targeting of specific neural progenitor regions. In order
      to illuminate the potential functional role that adult hypothalamic neurogenesis
      plays in the regulation of physiological processes, we developed a noninvasive
      focal irradiation technique to selectively inhibit the birth of adult-born
      neurons in the hypothalamic median eminence. We describe a method for Computer
      tomography-guided focal irradiation (CFIR) delivery to enable precise and
      accurate anatomical targeting in small animals. CFIR uses three-dimensional
      volumetric image guidance for localization and targeting of the radiation dose,
      minimizes radiation exposure to nontargeted brain regions, and allows for
      conformal dose distribution with sharp beam boundaries. This protocol allows one
      to ask questions regarding the function of adult-born neurons, but also opens
      areas to questions in areas of radiobiology, tumor biology, and immunology. These
      radiological tools will facilitate the translation of discoveries at the bench to
      the bedside. 

PMID- 24300417
TI  - Mechanisms of obesity in asthma.
AB  - PURPOSE OF REVIEW: Obesity and asthma are chronic conditions affecting millions
      of people worldwide. The two conditions also appear to be linked with an
      increased risk of asthma in people who are obese. The purpose of this review is
      to describe mechanism(s) that may explain the association between asthma and
      obesity. RECENT FINDINGS: Current evidence suggests that the association between
      asthma and obesity is linked by two major phenotypes and three important pathways
      of obesity-related asthma: one phenotype with primary (often atopic) asthma that
      is aggravated by obesity and a second phenotype with late-onset nonatopic asthma,
      which predominantly affects women and primarily seems to be associated with
      neutrophilic inflammation. Proposed pathways include the mechanical effects of
      obesity (fewer deep inspirations leading to increased airway
      hyperresponsiveness), an inflammatory pathway driven by obesity-related cytokines
      (adipokines), and finally environment and lifestyle changes that have led to an
      increasing prevalence of obesity over the past 50 years (including exposures in
      utero, physical activity, and diet) may also result in asthma in predisposed
      individuals. How these environmental changes influence the occurrence and
      expression of asthma may depend on the age of exposure and on interactions with
      genetic susceptibilities. SUMMARY: Future research should be directed to shed
      light on the associations between obesity and asthma phenotypes, modern
      lifestyles and environmental exposures and genetic susceptibilities. VIDEO
      ABSTRACT: http://links.lww.com/COAI/A6.

PMID- 24300418
TI  - The rhinitis control assessment test: implications for the present and future.
AB  - PURPOSE OF REVIEW: To summarize the development of the Rhinitis Control
      Assessment Test (RCAT), its usefulness in clinical practice, and the benefit it
      provides for patients who are bothered by allergic and nonallergic rhinitis.
      RECENT FINDINGS: The RCAT, a simple, brief, self-administered questionnaire, was
      developed to assist physicians in the assessment of patient's rhinitis control in
      clinical practice. It was also to help patients appreciate what rhinitis control
      is. The RCAT generates a rhinitis score that can be easily understood and is
      appropriate for long-term monitoring of rhinitis control. SUMMARY: Rhinitis
      control remains an elusive goal for physicians and patients. Having a patient
      rated screening instrument, like the RCAT, to assist in achieving this goal was
      felt to be important. If used appropriately, it reflects the multidimensional
      aspect of rhinitis control. It should also result in an improvement in the
      quality of care for patients with rhinitis.

PMID- 24300420
TI  - An update on the pathogenesis of the upper airways in aspirin-exacerbated
      respiratory disease.
AB  - PURPOSE OF REVIEW: The key features of aspirin-exacerbated respiratory diseases
      (AERDs) include chronic, severe asthma and a high prevalence (60-80%) of chronic
      rhinosinusitis with nasal polyps, all of which are exacerbated by exposure to
      aspirin and other NSAIDs. Although the pathogenic mechanisms of AERD are not
      completely understood, repeated instances have shown intense eosinophilic
      infiltrations of upper and lower airway mucosa, and dysregulation of arachidonate
      metabolisms. Here, recent updates on the pathogenic mechanisms of chronic
      rhinosinusitis with nasal polyps in aspirin-exacerbated respiratory diseases are
      summarized. RECENT FINDINGS: Intense eosinophilic infiltration is closely related
      to the elevated production of cytokines and chemokines such as IL-5 and eotaxin.
      The response of local immunoglobulin E to staphylococcal enterotoxins contributes
      to eosinophilic inflammation in nasal polyp tissue. Other characteristics include
      the overproduction of cysteinyl leukotrienes and increased expression of
      cysteinyl leukotriene receptor-1, reduced production of prostaglandin E2, and the
      down-regulation of cyclooxygenase-2 and E-prostanoid receptor subtype-2. A recent
      gene expression profiling study has also suggested that periostin is the most up
      regulated gene in the nasal polyp tissue of AERD patients. SUMMARY: Chronic
      rhinosinusitis with nasal polyps is a major comorbid condition of AERD patients
      that is closely associated with severe asthmatic symptoms. Significant pathologic
      findings in nasal polyp tissues include intense eosinophilic inflammation, which
      is caused by elevated production of eosinophil-related cytokines and chemokines,
      specific immunoglobulin E responses to staphylococcal enterotoxins, and altered
      arachidonic acid metabolism. This could affect the current treatments and
      methodologies that are used to control asthma, leading to a more severe and
      intractable AERD phenotype.

PMID- 24300419
TI  - Dendritic cell c-kit signaling and adaptive immunity: implications for the upper
      airways.
AB  - PURPOSE OF REVIEW: Binding of the receptor tyrosine kinase, c-kit, to its ligand,
      stem cell factor (SCF), mediates numerous biological functions. Important roles
      for c-kit in hematopoiesis, melanogenesis, erythropoiesis, spermatogenesis, and
      carcinogenesis are well documented. Similarly, activation of mast cells and
      eosinophils by c-kit ligation has long been known to result in degranulation with
      concomitant release of pro-inflammatory mediators including cytokines. This
      review will highlight a recently discovered function of c-kit in regulating the
      adaptive immune responses with relevance to allergic diseases. RECENT FINDINGS:
      Recent studies in a number of laboratories including our own highlight the
      previously unappreciated functions for c-kit in immunological processes.
      Increased expression of c-kit and its ligand, SCF, on dendritic cells by Th2/Th17
      inducing stimuli leads to c-kit activation and immune skewing toward these
      subsets and away from Th1 responses. Treatment of dendritic cells with inhibitors
      of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell
      tolerance, skewing of responses toward Th1, and activation of natural killer
      cells. SUMMARY: Taken together, these observations suggest that the c-kit/SCF
      axis may be a useful target for redirecting deleterious immune responses in
      various disease settings, including allergic diseases that are often associated
      with Th2 and Th17 responses.

PMID- 24300421
TI  - Elements of concern in fillets of bighead and silver carp from the Illinois
      River, Illinois.
AB  - Efforts to control invasive bighead (Hypophthalmichthys nobilis) and silver carp
      (H. molitrix) may include harvest for human consumption. We measured
      concentrations of arsenic (As), mercury (Hg), and selenium (Se) in fillets from
      silver and bighead carp collected from the lower Illinois River, Illinois, USA,
      to determine whether concentrations were of health concern and differed by
      species, size, and location. Concentrations of total As were below detection
      limits in most bighead (92%) and silver (77%) carp fillets, whereas inorganic As
      was below detection limits in all samples. Mean Hg concentrations were greater in
      bighead (0.068 mg kg(-1)) than in silver carp (0.035 mg kg(-1)), and were
      smallest in carp from the confluence of the Illinois and Mississippi rivers.
      Mercury concentrations in fillets were positively correlated with body mass in
      both species. Concentrations of Hg were below the US Food and Drug
      Administration's (USFDA) action level (1 ppm as methyl-Hg); however,
      concentrations in some bighead (70%) and silver (12%) carp fell within the range
      that would invoke a recommendation to limit meals in sensitive cohorts. Mean Se
      concentrations were greater in silver (0.332 mg kg(-1)) than in bighead (0.281 mg
      kg(-1)) carp fillets, and were below the 1.5 mg kg(-1) limit for an unrestricted
      number of meals/month. The mean molar ratio of Se:Hg in fillets was lower in
      bighead (14.0) than in silver (29.1) carp and was negatively correlated with mass
      in both species Concentrations of Hg in bighead and silver carp fillets should be
      considered when assessing the risks associated with the use of these species as a
      protein source.

PMID- 24300422
TI  - 2014 case management prognostications.
AB  - 2014 Healthcare predictions affecting case management are an inexact science.
      However, some issues will continue to be front and center as we navigate a health
      care environment that is changing at the speed of, well, health care. 

PMID- 24300423
TI  - COLLABORATE(c): a universal competency-based paradigm for professional case
      management, Part III: key considerations for making the paradigm shift.
AB  - PURPOSE/OBJECTIVES: The purpose of the third of this 3-article series is to
      provide context and justification for a new paradigm of case management built
      upon a value-driven foundation that * improves the patient's experience of health
      care delivery, * provides consistency in approach applicable across health care
      populations, and * optimizes the potential for return on investment. PRIMARY
      PRACTICE SETTING(S): Applicable to all health care sectors where case management
      is practiced. FINDINGS/CONCLUSIONS: In moving forward the one fact that rings
      true is there will be constant change in our industry. As the health care terrain
      shifts and new influences continually surface, there will be consequences for
      case management practice. These impacts require nimble clinical professionals in
      possession of recognized and firmly established competencies. They must be agile
      to frame (and reframe) their professional practice to facilitate the best
      possible outcomes for their patients. Case managers can choose to be Gumby or
      Pokey. This is exactly why the definition of a competency-based case management
      model's time has come, one sufficiently fluid to fit into any setting of care.
      IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The practice of case management
      transcends the vast array of representative professional disciplines and
      educational levels. A majority of current models are driven by business
      priorities rather than the competencies critical to successful practice and
      quality patient outcomes. This results in a fragmented professional case
      management identity. While there is inherent value in what each discipline brings
      to the table, this advanced model unifies behind case management's unique,
      strengths-based identity instead of continuing to align within traditional
      divisions (e.g., discipline, work setting, population served). This model fosters
      case management's expanding career advancement opportunities, including a
      reflective clinical ladder.

PMID- 24300425
TI  - Are we prepared for Affordable Care Act provisions of care coordination? Case
      managers' self-assessments and views on physicians' roles.
AB  - PURPOSE OF STUDY: Care coordination, traditionally the purview of the case
      management field, is recognized as a national priority for improving health care
      delivery and patient outcomes. With reforms of the Affordable Care Act (ACA) of
      2010, case managers face new challenges and opportunities in providing care
      coordination services. The evolving roles of case managers as members of
      interprofessional care teams will be influenced by new policies that enable
      physicians to be reimbursed for care coordination. This qualitative study aimed
      to evaluate case managers' self-assessed readiness for ACA reforms of care
      coordination and their perceptions of physicians' understanding of case
      management and ability to lead care coordination efforts in evolving models.
      PRIMARY PRACTICE SETTINGS: Provisions of care coordination in the ACA affect case
      managers in all practice settings. The majority of this study's participants
      represented hospital and managed care settings. METHODOLOGY AND SAMPLE: An
      invitation to complete an 11-item online survey was sent by e-mail to 8,110 case
      managers in an opt-in database maintained by a health care continuing education
      company. Survey questions were designed to assess respondents' (1) self-reported
      levels of knowledge and preparation for ACA care coordination provisions and (2)
      beliefs about the readiness and abilities of physicians to administer care
      coordination services. In addition, demographic data and open-ended comments
      regarding physicians' roles in conducting care coordination were collected. Over
      a restricted 9-day period, 834 case managers representing various health care
      settings responded to the survey. RESULTS: The majority of respondents (63%)
      indicated that more than 50% of their day is dedicated to performing care
      coordination activities. However, 80% of all respondents reported being "not at
      all knowledgeable" or only "somewhat knowledgeable" about the new care
      coordination provisions in the ACA. Only 8% admitted to being "very prepared" to
      implement ACA changes. The majority of respondents (68%) perceive their case
      management departments to be at least "somewhat prepared" to implement necessary
      changes. Whereas 67% of respondents expect physicians to have at least a
      "moderate role" in implementing care coordination services, only 12% believe that
      physicians have more than "some" understanding of the processes of care
      coordination and case managers' roles. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      These qualitative study findings suggest that case managers from multiple
      practice settings perceive a lack of preparedness, knowledge, and understanding
      among themselves and physicians regarding ACA reforms that may significantly
      affect the delivery of care coordination services. The findings call for new
      initiatives in interprofessional education to address the knowledge gaps and
      enhance understanding of the collaborative roles among case managers and
      physicians.

PMID- 24300428
TI  - The Affordable Care Act state health insurance marketplaces: a toolkit for case
      managers.

PMID- 24300427
TI  - Impact of discharge planning decision support on time to readmission among older
      adult medical patients.
AB  - PURPOSE OF THE STUDY: Hospital clinicians are overwhelmed with the volume of
      patients churning through the health care systems. The study purpose was to
      determine whether alerting case managers about high-risk patients by supplying
      decision support results in better discharge plans as evidenced by time to first
      hospital readmission. PRIMARY PRACTICE SETTING: Four medical units at one urban,
      university medical center. METHODOLOGY AND SAMPLE: A quasi-experimental study
      including a usual care and experimental phase with hospitalized English-speaking
      patients aged 55 years and older. The intervention included using an evidence
      based screening tool, the Discharge Decision Support System (D2S2), that supports
      clinicians' discharge referral decision making by identifying high-risk patients
      upon admission who need a referral for post-acute care. The usual care phase
      included collection of the D2S2 information, but not sharing the information with
      case managers. The experimental phase included data collection and then sharing
      the results with the case managers. The study compared time to readmission
      between index discharge date and 30 and 60 days in patients in both groups (usual
      care vs. experimental). RESULTS: After sharing the D2S2 results, the percentage
      of referral or high-risk patients readmitted by 30 and 60 days decreased by 6%
      and 9%, respectively, representing a 26% relative reduction in readmissions for
      both periods. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Supplying decision
      support to identify high-risk patients recommended for postacute referral is
      associated with better discharge plans as evidenced by an increase in time to
      first hospital readmission. The tool supplies standardized information upon
      admission allowing more time to work with high-risk admissions.

PMID- 24300430
TI  - The multigenerational workforce.

PMID- 24300431
TI  - Advocacy--our most important role.

PMID- 24300432
TI  - Angela Dunham: helping to lead case managers and case management.

PMID- 24300433
TI  - Amid the parade of "white coats"--personalizing patient-centered health care.

PMID- 24300435
TI  - Autophagy suppresses melanoma tumorigenesis by inducing senescence.
AB  - Whether and how autophagy is involved in tumorigenesis is poorly understood. We
      approached this question by investigating a relatively large cohort of patients
      with mostly early primary melanoma for their expression of 2 markers for
      autophagy, the protein ATG5 (autophagy-related 5) and MAP1LC3B/LC3 (microtubule
      associated protein 1 light chain 3B). Surprisingly, we discovered that both ATG5
      and LC3 levels are decreased in patients with melanomas as compared with those
      with benign nevi. We wondered why reduced autophagy should facilitate early tumor
      development. Using an in vitro model of melanoma tumorigenesis, in which a
      mutated oncogene, BRAF (v-raf murine sarcoma viral oncogene homolog B), had been
      introduced into normal human melanocytes, we were able to show that
      downregulation of ATG5 promoted the proliferation of melanocytes because it
      facilitated bypassing oncogene-induced senescence (OIS). Our work supports
      previous reports that had argued that autophagy actually suppresses tumorigenesis
      and explains the possible mechanism. Furthermore, our findings suggest that the
      status of ATG5 and autophagy could serve as a diagnostic marker for
      distinguishing benign from malignant tumors of melanocytes. 

PMID- 24300434
TI  - Polyunsaturated fatty acid associations with dopaminergic indices in major
      depressive disorder.
AB  - Dopaminergic function is thought to be altered in major depression and, in animal
      studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency
      states. Therefore we studied PUFAs and resting prolactin, a marker for
      dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief
      dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major
      depressive disorder (MDD), we measured plasma phospholipid levels of omega-3
      PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6
      PUFA arachidonic acid (AA), and plasma prolactin levels before and after
      administration of dl-fenfluramine (FEN). In a subset of patients (n = 14),
      cerebrospinal fluid levels of HVA and the serotonin metabolite, 5
      hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture.
      Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F(1,21)
      = 20.380, p < 0.001; logEPA, F(1,21) = 10.051, p = 0.005) and positively
      correlated with logAA:DHA (F(1,21) = 15.263, p = 0.001), a measure of omega
      6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's rho
      = -0.675, p = 0.008) but not 5-HIAA (Spearman's rho = -0.143, p = 0.626) after
      controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the
      magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin
      effect. The robust relationship of omega-3 PUFAs with dopaminergic but not
      serotonergic indices suggests that omega-6:omega-3 balance may impact depression
      pathophysiology through effects on the dopaminergic system.

PMID- 24300436
TI  - Breastfeeding and cardiometabolic profile in childhood: how infant feeding,
      preterm birth, socioeconomic status, and obesity may fit into the puzzle.

PMID- 24300438
TI  - ISRNA: an integrative online toolkit for short reads from high-throughput
      sequencing data.
AB  - Integrative Short Reads NAvigator (ISRNA) is an online toolkit for analyzing high
      throughput small RNA sequencing data. Besides the high-speed genome mapping
      function, ISRNA provides statistics for genomic location, length distribution and
      nucleotide composition bias analysis of sequence reads. Number of reads mapped to
      known microRNAs and other classes of short non-coding RNAs, coverage of short
      reads on genes, expression abundance of sequence reads as well as some other
      analysis functions are also supported. The versatile search functions enable
      users to select sequence reads according to their sub-sequences, expression
      abundance, genomic location, relationship to genes, etc. A specialized genome
      browser is integrated to visualize the genomic distribution of short reads. ISRNA
      also supports management and comparison among multiple datasets. AVAILABILITY:
      ISRNA is implemented in Java/C++/Perl/MySQL and can be freely accessed at
      http://omicslab.genetics.ac.cn/ISRNA/.

PMID- 24300437
TI  - Effects of promoting longer-term and exclusive breastfeeding on cardiometabolic
      risk factors at age 11.5 years: a cluster-randomized, controlled trial.
AB  - BACKGROUND: The duration and exclusivity of breastfeeding in infancy have been
      inversely associated with future cardiometabolic risk. We investigated the
      effects of an experimental intervention to promote increased duration of
      exclusive breastfeeding on cardiometabolic risk factors in childhood. METHODS AND
      RESULTS: We followed-up children in the Promotion of Breastfeeding Intervention
      Trial, a cluster-randomized trial of a breastfeeding promotion intervention based
      on the World Health Organization/United Nations Children's Fund Baby-Friendly
      Hospital Initiative. In 1996 to 1997, 17 046 breastfeeding mother-infant pairs
      were enrolled from 31 Belarusian maternity hospitals and affiliated polyclinics
      (16 intervention versus 15 control sites); 13 879 (81.4%) children were followed
      up at 11.5 years, with 13 616 (79.9%) who had fasted and did not have diabetes
      mellitus. The outcomes were blood pressure; fasting insulin, adiponectin,
      glucose, and apolipoprotein A1; and the presence of metabolic syndrome. Analysis
      was by intention to treat, accounting for clustering within hospitals/clinics.
      The intervention substantially increased breastfeeding duration and exclusivity
      in comparison with the control arm (43% versus 6% and 7.9% versus 0.6%
      exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean
      differences at 11.5 years between experimental versus control groups were as
      follows: 1.0 mm Hg (95% confidence interval, -1.1 to 3.1) for systolic and 0.8 mm
      Hg (-0.6 to 2.3) for diastolic blood pressure; -0.1 mmol/L (-0.2 to 0.1) for
      glucose; 8% (-3% to 34%) for insulin; -0.3 MUg/mL (-1.5 to 0.9) for adiponectin;
      and 0.0 g/L (-0.1 to 0.1) for apolipoprotein A1. The cluster-adjusted odds ratio
      for metabolic syndrome, comparing experimental versus control groups, was 1.21
      (0.85 to 1.72). CONCLUSIONS: An intervention to improve breastfeeding duration
      and exclusivity among healthy term infants did not influence cardiometabolic risk
      factors in childhood. CLINICAL TRIAL REGISTRATION: Current Controlled Trials:
      ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716). URL:
      http://clinicaltrials.gov. Unique identifier: NCT01561612.

PMID- 24300440
TI  - Rapid synthesis and screening of chemically activated transcription factors with
      GFP-based reporters.
AB  - Synthetic biology aims to rationally design and build synthetic circuits with
      desired quantitative properties, as well as provide tools to interrogate the
      structure of native control circuits. In both cases, the ability to program gene
      expression in a rapid and tunable fashion, with no off-target effects, can be
      useful. We have constructed yeast strains containing the ACT1 promoter upstream
      of a URA3 cassette followed by the ligand-binding domain of the human estrogen
      receptor and VP16. By transforming this strain with a linear PCR product
      containing a DNA binding domain and selecting against the presence of URA3, a
      constitutively expressed artificial transcription factor (ATF) can be generated
      by homologous recombination. ATFs engineered in this fashion can activate a
      unique target gene in the presence of inducer, thereby eliminating both the off
      target activation and nonphysiological growth conditions found with commonly used
      conditional gene expression systems. A simple method for the rapid construction
      of GFP reporter plasmids that respond specifically to a native or artificial
      transcription factor of interest is also provided. 

PMID- 24300441
TI  - Prevalence of viral pathogens WSSV and IHHNV in wild organisms at the Pacific
      Coast of Mexico.
AB  - This study investigated whether white spot syndrome virus and Infectious
      hypodermal and hematopoietic necrosis virus, can survive in wild invertebrates
      and vertebrates in the environment surrounding shrimp farms along the Pacific
      coast of Mexico. The evidences imply that both viruses have a potential of
      persisting in crabs, blue, white and brown shrimps. The most prevalent virus,
      IHHNV was present in 19.5% (344/1736) followed by WSSV in 3.6% (65/1736).
      Coinfection of WSSV and IHHNV was also detected in crabs, blue and white shrimps.
      This is the first prevalence report of WSSV and IHHNV associated with wildlife
      species in Mexico. 

PMID- 24300439
TI  - Automated annotation of developmental stages of Drosophila embryos in images
      containing spatial patterns of expression.
AB  - MOTIVATION: Drosophila melanogaster is a major model organism for investigating
      the function and interconnection of animal genes in the earliest stages of
      embryogenesis. Today, images capturing Drosophila gene expression patterns are
      being produced at a higher throughput than ever before. The analysis of spatial
      patterns of gene expression is most biologically meaningful when images from a
      similar time point during development are compared. Thus, the critical first step
      is to determine the developmental stage of an embryo. This information is also
      needed to observe and analyze expression changes over developmental time.
      Currently, developmental stages (time) of embryos in images capturing spatial
      expression pattern are annotated manually, which is time- and labor-intensive.
      Embryos are often designated into stage ranges, making the information on
      developmental time course. This makes downstream analyses inefficient and
      biological interpretations of similarities and differences in spatial expression
      patterns challenging, particularly when using automated tools for analyzing
      expression patterns of large number of images. RESULTS: Here, we present a new
      computational approach to annotate developmental stage for Drosophila embryos in
      the gene expression images. In an analysis of 3724 images, the new approach shows
      high accuracy in predicting the developmental stage correctly (79%). In addition,
      it provides a stage score that enables one to more finely annotate each embryo so
      that they are divided into early and late periods of development within standard
      stage demarcations. Stage scores for all images containing expression patterns of
      the same gene enable a direct way to view expression changes over developmental
      time for any gene. We show that the genomewide-expression-maps generated using
      images from embryos in refined stages illuminate global gene activities and
      changes much better, and more refined stage annotations improve our ability to
      better interpret results when expression pattern matches are discovered between
      genes. AVAILABILITY AND IMPLEMENTATION: The software package is availablefor
      download at: http://www.public.asu.edu/*jye02/Software/Fly-Project/.

PMID- 24300442
TI  - A five-year field assessment of rapid diagnostic tests for meningococcal
      meningitis in Niger by using the combination of conventional and real-time PCR
      assays as a gold standard.
AB  - BACKGROUND: Meningococcocal meningitis represents an important cause of mortality
      and morbidity in sub-Saharan countries. Confirmatory bacteriological or molecular
      diagnosis is essential for patient management/treatment and meningitis
      surveillance, but many laboratory tests are expensive and rarely available for
      low-income countries. A rapid diagnostic test (RDT) represents a valuable
      alternative to improve case management and surveillance. METHODS: A dipstick RDT
      developed in early 2000s that detects Neisseria meningitidis serogroups A, C, W
      and Y but for which a new conjugated antibody (L4-8) for the detection of
      serogroup A replaced the original K15-2 was assessed in the field by trained
      staff from health centres and district hospitals in Niger. The results were
      compared to those obtained in the reference laboratory and the sensitivity and
      specificity of RDTs were determined using conventional and real-time PCR assays
      as a gold standard. RESULTS: RDT results from field staff and the reference
      laboratory obtained for 2095 cerebrospinal fluid (CSF) specimens presented a
      strong concordance of 94% with Cohen's kappa coefficient of 0.88. The observed
      concordance between RDTs operated by staff from the reference laboratory vs
      combination of conventional and real-time PCR assays was 89% with Cohen's kappa
      coefficient of 0.76 indicating very good agreement. The theoretical overall
      sensitivity for RDT was 91.5% and the specificity 84.6%. CONCLUSIONS: RDT has
      proven to be relatively sensitive and specific for the detection of meningococcal
      serogroups A/C/Y/W. We confirmed that these RDTs can be reliably operated by
      trained but non-specialised staff in basic health facilities.

PMID- 24300443
TI  - Does a significant reduction in malaria risk make lopinavir/ritonavir-based ART
      cost-effective for children with HIV in co-endemic, low-resource settings?
AB  - BACKGROUND: HIV infection and malaria co-infection is not uncommon among children
      in co-endemic regions, and evidence suggests that HIV is a risk factor for severe
      malaria among children. HIV protease inhibitors (PIs) are highly effective in
      pediatric HIV treatment regimens, however, their effectiveness against malaria
      has been mixed, with some PIs demonstrating in vitro activity against Plasmodium
      falciparum. Recent findings suggest lopinavir/ritonavir (LPV/r)-based treatment
      regimens reduce the incidence of malaria infection by over 40% in pediatric HIV
      patients compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based
      regimens. METHODS: We assessed whether a significant reduction in malaria risk
      makes LPV/r-based ART regimens cost-effective compared to NNRTI-based regimens in
      co-endemic, low-resource settings. We modeled the difference in unit cost per
      disability adjusted life year (DALY) gained among two theoretical groups of HIV+
      children under 5 years old receiving ART in a resource-limited setting co-endemic
      for malaria. The first group received standard NNRTI-based antiretrovirals, the
      second group received a standard regimen containing LPV/r. We used recent cohort
      data for the incidence reduction for malaria. Drug costs were taken from the 2011
      Clinton Health Access Initiative Antiretroviral (ARV) ceiling price list. DALYs
      for HIV and malaria were derived from WHO estimates. RESULTS: Our model suggests
      a unit cost of US$147 per DALY gained for the LPV/r-based group compared to US$37
      per DALY gained for the NNRTI-based group. CONCLUSION: In HIV and malaria co
      endemic settings, considerations of PI cost effectiveness incorporating known
      reductions in malaria mortality suggest a nominal increase in DALYs gained for
      PIs over NNRTI-based regimens for HIV positive children under five on ART. Our
      analysis was based on several assumptions due to lack of sound data on malaria
      and HIV DALY attribution among pediatric populations. Further study in this area
      is required.

PMID- 24300444
TI  - How can we bring high drug doses to the lung?
AB  - In the last decades, dry powder inhalation has become a very attractive option
      for pulmonary drug delivery to treat lung diseases like cystic fibroses and lung
      infections. In contrast to the traditional pulmonary application of drugs for
      asthma and chronic obstructive pulmonary disease, these therapies require higher
      lung doses to be administered. The developments and improvements toward high dose
      powder pulmonary drug delivery are summarized and discussed in this chapter.
      These include the invention and improvement of novel inhaler devices as well as
      the further development of formulation principles and new powder engineering
      methods. The implementation of these strategies is subsequently described for
      some prototypes and formulations in research and development stage as well as for
      already marketed dry powder products. Finally, possible adverse effects that can
      occur after inhalation of high powder doses are shortly addressed. 

PMID- 24300445
TI  - FtsZ polymerization assays: simple protocols and considerations.
AB  - During bacterial cell division, the essential protein FtsZ assembles in the
      middle of the cell to form the so-called Z-ring. FtsZ polymerizes into long
      filaments in the presence of GTP in vitro, and polymerization is regulated by
      several accessory proteins. FtsZ polymerization has been extensively studied in
      vitro using basic methods including light scattering, sedimentation, GTP
      hydrolysis assays and electron microscopy. Buffer conditions influence both the
      polymerization properties of FtsZ, and the ability of FtsZ to interact with
      regulatory proteins. Here, we describe protocols for FtsZ polymerization studies
      and validate conditions and controls using Escherichia coli and Bacillus subtilis
      FtsZ as model proteins. A low speed sedimentation assay is introduced that allows
      the study of the interaction of FtsZ with proteins that bundle or tubulate FtsZ
      polymers. An improved GTPase assay protocol is described that allows testing of
      GTP hydrolysis over time using various conditions in a 96-well plate setup, with
      standardized incubation times that abolish variation in color development in the
      phosphate detection reaction. The preparation of samples for light scattering
      studies and electron microscopy is described. Several buffers are used to
      establish suitable buffer pH and salt concentration for FtsZ polymerization
      studies. A high concentration of KCl is the best for most of the experiments. Our
      methods provide a starting point for the in vitro characterization of FtsZ, not
      only from E. coli and B. subtilis but from any other bacterium. As such, the
      methods can be used for studies of the interaction of FtsZ with regulatory
      proteins or the testing of antibacterial drugs which may affect FtsZ
      polymerization. 

PMID- 24300446
TI  - Intravital microscopy of the microcirculation in the mouse cremaster muscle for
      the analysis of peripheral stem cell migration.
AB  - In the era of intravascular cell application protocols in the context of
      regenerative cell therapy, the underlying mechanisms of stem cell migration to
      nonmarrow tissue have not been completely clarified. We describe here the
      technique of intravital microscopy applied to the mouse cremaster
      microcirculation for analysis of peripheral bone marrow stem cell migration in
      vivo. Intravital microscopy of the M. cremaster has been previously introduced in
      the field of inflammatory research for direct observation of leucocyte
      interaction with the vascular endothelium. Since sufficient peripheral stem and
      progenitor cell migration includes similar initial steps of rolling along and
      firm adhesion at the endothelial lining it is conceivable to apply the M.
      cremaster model for the observation and quantification of the interaction of
      intravasculary administered stem cells with the endothelium. As various chemical
      components can be selectively applied to the target tissue by simple superfusion
      techniques, it is possible to establish essential microenvironmental
      preconditions, for initial stem cell recruitment to take place in a living
      organism outside the bone marrow. 

PMID- 24300447
TI  - Glutathione Transferase (GST)-Activated Prodrugs.
AB  - Glutathione transferase (formerly GST) catalyzes the inactivation of various
      electrophile-producing anticancer agents via conjugation to the tripeptide
      glutathione. Moreover, several data link the overexpression of some GSTs, in
      particular GSTP1-1, to both natural and acquired resistance to various
      structurally unrelated anticancer drugs. Tumor overexpression of these proteins
      has provided a rationale for the search of GST inhibitors and GST activated
      cytotoxic prodrugs. In the present review we discuss the current structural and
      pharmacological knowledge of GST-activated cytotoxic compounds. 

PMID- 24300448
TI  - Design, synthesis and in vitro degradation of a novel co-drug for the treatment
      of psoriasis.
AB  - Psoriasis is a common, chronic and relapsing inflammatory skin disease. It
      affects approximately 2% of the western population and has no cure. Combination
      therapy for psoriasis often proves more efficacious and better tolerated than
      monotherapy with a single drug. Combination therapy could be administered in the
      form of a co-drug, where two or more therapeutic compounds active against the
      same condition are linked by a cleavable covalent bond. Similar to the pro-drug
      approach, the liberation of parent moieties post-administration, by enzymatic
      and/or chemical mechanisms, is a pre-requisite for effective treatment. In this
      study, a series of co-drugs incorporating dithranol in combination with one of
      several non-steroidal anti-inflammatory drugs, both useful for the treatment of
      psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising
      dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess
      the optimal physicochemical properties for topical delivery. The co-drug was
      fully hydrolyzed in vitro by porcine liver esterase within four hours. When
      incubated with homogenized porcine skin, 9.5% of the parent compounds were
      liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co
      drug would occur within the skin. The kinetics of the reaction revealed first
      order kinetics, Vmax = 10.3 MUM.min-1 and Km = 65.1 MUM. The co-drug contains a
      modified dithranol chromophore that was just 37% of the absorbance of dithranol
      at 375 nm and suggests reduced skin/clothes staining. Overall, these findings
      suggest that the dithranol-naproxen co-drug offers an attractive, novel approach
      for the treatment of psoriasis. 

PMID- 24300449
TI  - Development of a novel lipophilic, magnetic nanoparticle for in vivo drug
      delivery.
AB  - The aim of the present study was to evaluate the transfection potential of
      chitosan-coated, green-fluorescent magnetic nanoparticles (MNPs) (chi-MNPs) after
      encapsulation inside polyethylglycol (PEG)ylated liposomes that produced lipid
      encapsulated chitosan-coated MNPs (lip-MNPs), and also to evaluate how these
      particles would distribute in vivo after systemic injection. The transfection
      potential of both chi-MNPs and lip-MNPs was evaluated in vitro in rat brain
      endothelial 4 (RBE4) cells with and without applying a magnetic field.
      Subsequently, the MNPs were evaluated in vivo in young rats. The in vitro
      investigations revealed that the application of a magnetic field resulted in an
      increased cellular uptake of the particles. The lip-MNPs were able to transfect
      the RBE4 cells with an incidence of approximately 20% of a commercial
      transfection agent. The in vivo distribution studies revealed that lip-MNPs had
      superior pharmacokinetic properties due to evasion of the RES, including hepatic
      Kuppfer cells and macrophages in the spleen. In conclusion, we were able to
      design a novel lipid-encapsulated MNP with the ability to carry genetic material,
      with favorable pharmacokinetic properties, and under the influence of a magnetic
      field with the capability to mediate transfection in vitro. 

PMID- 24300450
TI  - Preclinical absorption, distribution, metabolism, and excretion of an oral amide
      prodrug of gemcitabine designed to deliver prolonged systemic exposure.
AB  - Gemcitabine is an intravenously administered nucleoside analog chemotherapeutic
      agent. The ability to deliver this agent as an oral drug would allow greater
      flexibility of administration and patient convenience; however, attempts have
      been fraught with high first-pass metabolism and potential intestinal toxicity.
      Alternatively, an amide prodrug of gemcitabine (LY2334737) was discovered, which
      is able to avoid the extensive first-pass metabolism that occurs following
      administration of gemcitabine. Preclinical in vitro and in vivo experiments were
      conducted to evaluate the hydrolysis and pharmacokinetics of LY2334737 and its
      downstream metabolites. In mice, rats, and dogs, the prodrug is absorbed largely
      intact across the intestinal epithelium and delivers LY2334737 to systemic
      circulation. The hydrolysis of LY2334737 is relatively slow, resulting in
      sustained release of gemcitabine in vivo. In vitro experiments identified
      carboxylesterase 2 (CES2) as a major enzyme involved in the hydrolysis of
      LY2334737, but with relatively low intrinsic clearance. Following hydrolysis of
      the prodrug, gemcitabine is cleared predominantly via the formation of its
      inactive metabolite dFdU. Both biliary and renal excretion was responsible for
      the elimination of LY2334737 and its metabolites in both mice and dogs. 

PMID- 24300451
TI  - Encapsulation of hydrocortisone and mesalazine in zein microparticles.
AB  - Zein was investigated for use as an oral-drug delivery system by loading
      prednisolone into zein microparticles using coacervation. To investigate the
      adaptability of this method to other drugs, zein microparticles were loaded with
      hydrocortisone, which is structurally related to prednisolone; or mesalazine,
      which is structurally different having a smaller LogP and ionizable functional
      groups. Investigations into the in vitro digestibility, and the electrophoretic
      profile of zein, and zein microparticles were conducted to shed further insight
      on using this protein as a drug delivery system. Hydrocortisone loading into zein
      microparticles was comparable with that reported for prednisolone, but mesalazine
      loading was highly variable. Depending on the starting quantities of
      hydrocortisone and zein, the average amount of microparticles equivalent to 4 mg
      hydrocortisone, (a clinically used dose), ranged from 60-115 mg, which is
      realistic and practical for oral dosing. Comparatively, an average of 2.5 g of
      microparticles was required to deliver 250 mg of mesalazine (a clinically used
      dose), so alternate encapsulation methods that can produce higher and more
      precise mesalazine loading are required. In vitro protein digestibility revealed
      that zein microparticles were more resistant to digestion compared to the zein
      raw material, and that individual zein peptides are not preferentially
      coacervated into the microparticles. In combination, these results suggest that
      there is potential to formulate a delivery system based on zein microparticles
      made using specific subunits of zein that is more resistant to digestion as
      starting material, to deliver drugs to the lower gastrointestinal tract. 

PMID- 24300452
TI  - Delivery of cancer therapeutics using nanotechnology.
AB  - Nanoparticles have been investigated as drug carriers, because they provide a
      great opportunity due to their advantageous features: (i) various formulations
      using organic/inorganic materials, (ii) easy modification of targeting molecules,
      drugs or other molecules on them, (iii) effective delivery to target sites,
      resulting in high therapeutic efficacy and (iv) controlling drug release by
      external/internal stimuli. Because of these features, therapeutic efficacy can be
      improved and unwanted side effects can be reduced. Theranostic nanoparticles have
      been developed by incorporating imaging agents in drug carriers as all-in-one
      system, which makes it possible to diagnose and treat cancer by monitoring drug
      delivery behavior simultaneously. Recently, stimuli-responsive, activatable
      nanomaterials are being applied that are capable of producing chemical or
      physical changes by external stimuli. By using these nanoparticles, multiple
      tasks can be carried out simultaneously, e.g., early and accurate diagnosis,
      efficient cataloguing of patient groups of personalized therapy and real-time
      monitoring of disease progress. In this paper, we describe various types of
      nanoparticles for drug delivery systems, as well as theranostic systems. 

PMID- 24300454
TI  - Towards reducing inequalities: European Standards of Care for Children with
      Cancer.
AB  - Despite the increase of cure rates in the treatment of children with cancer there
      is a significant discrepancy in the outcome within Europe. Data are showing us
      that there is a difference of 20% in outcomes for young people with cancer when
      comparing North and Western Europe with Central and Eastern Europe. One of the
      most important necessities, in order to be able to have comparable results and
      equitable outcomes about inequalities, is to have the Principle Treatment
      Centres, meeting a minimum level of standards and being accessible to
      continuously updated 'best practice'. The European Society of Paediatric Oncology
      (SIOPE) has initiated a study in order to monitor the current situation of the
      European Standards of Paediatric Oncology Centres. The results of the study
      showed disparities of Standards of Care in the Treatment Centres across Europe.
      Therefore SIOPE initiated a project aimed at improving the Quality-of-Care of
      children and adolescents with cancer and to assess the relevant organisational
      aspects within paediatric oncology. At the first European Union (EU) Conference
      in Warsaw 2009, an agreement was obtained from all involved stakeholders to
      initiate the creation of Pan-European guidelines entitled 'European Standards of
      Care for Children with Cancer'. The guidelines outlined in this document
      represent the minimum standards of care that should be implemented at the EU
      level. Describing the different aspects of Care over 15 chapters and available in
      more than 16 different EU languages these guidelines are used as tools for both
      professionals and parent/patients groups in order to advocate 'improved standards
      across EU'. 

PMID- 24300455
TI  - HER3 expression in patients with primary colorectal cancer and corresponding
      lymph node metastases related to clinical outcome.
AB  - AIM: To evaluate the expression and prognostic value of the epidermal growth
      factor receptor HER3 in patients with primary colorectal cancer (CRC) and
      corresponding lymph node metastases. PATIENT AND METHODS: HER3 expression was
      analysed immunohistochemically (IHC) in primary tumours and in corresponding
      lymph node metastases from 236 patients with stage II and III CRC. In 58 primary
      tumours, fluorescence in situ hybridisation (FISH) detection was performed.
      RESULTS: HER3 was detected at high frequency in the cell membrane. Seventy
      percent of the primary tumours had a high HER3 expression compared to 75% in the
      lymph node metastases. HER3 expression in the primary tumour was an independent
      prognostic factor for overall survival in the entire group of patients (p=0.026)
      and in the subgroup of patients with colon cancer stage II (p=0.030). A high HER3
      expression in the primary tumour was associated with worse clinical outcome. The
      expression of HER3 was homogenous within the primary tumour (r=0.9, p<0.0001) and
      correlated with the HER3 expression in corresponding lymph node metastases
      (r=0.6, p<0.0001). No gene amplification with respect to HER3 was seen in primary
      tumours using FISH analysis. CONCLUSION: A high HER3 expression was found in 70%
      of the primary CRC tumours and in 75% of the corresponding lymph node metastases.
      HER3 expression in the tumour was an independent prognostic factor, where a high
      HER3 expression was associated with worse clinical outcome. There was a
      correlation in HER3 expression between primary tumour and corresponding lymph
      node metastases.

PMID- 24300453
TI  - Polysaccharide-based micelles for drug delivery.
AB  - Delivery of hydrophobic molecules and proteins has been an issue due to poor
      bioavailability following administration. Thus, micelle carrier systems are being
      investigated to improve drug solubility and stability. Due to problems with
      toxicity and immunogenicity, natural polysaccharides are being explored as
      substitutes for synthetic polymers in the development of new micelle systems. By
      grafting hydrophobic moieties to the polysaccharide backbone, self-assembled
      micelles can be readily formed in aqueous solution. Many polysaccharides also
      possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting
      of specific tissues, and a reduction in the inflammatory response. Furthermore,
      the hydrophilic nature of some polysaccharides can be exploited to enhance
      circulatory stability. This review will highlight the advantages of
      polysaccharide use in the development of drug delivery systems and will provide
      an overview of the polysaccharide-based micelles that have been developed to
      date. 

PMID- 24300456
TI  - Redistribution of H3K27me3 and acetylated histone H4 upon exposure to azacitidine
      and decitabine results in de-repression of the AML1/ETO target gene IL3.
AB  - Human acute myeloid leukemia is characterized by a block in maturation caused by
      genetic and epigenetic alterations. We studied the effects of low concentrations
      of the DNA methyltransferase (DNMT) inhibitors 5-azacitidine and decitabine on
      apoptosis and on chromatin remodeling in an AML1/ETO inducible model of human
      AML. While both DNMT inhibitors induced apoptosis, only azacitidine did so via
      caspase activation, possibly through its exclusive non-DNA depending effects. We
      evaluated histone marks for permissive chromatin, H3K4me3, and acetylated histone
      H4, and for non-permissive chromatin, H3K9me2, and H3K27me3, at the promoter of
      the IL3 gene, which is under the direct control of AML1/ETO and is critical for
      myeloid maturation. We observed that low concentrations of DNMT inhibitors
      induced a loss of H3K27me3 and gain of acetylated histone H4 at the IL3 promoter
      exclusively in AML1/ETO-positive cells, which was associated with transcriptional
      reactivation of the IL3 gene. 

PMID- 24300457
TI  - Legacy and current-use brominated flame retardants in the Barn Owl.
AB  - The present study investigated the current-use brominated flame retardants (BFRs)
      tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD), simultaneously
      with legacy polybrominated diphenyl ethers (PBDEs), in Barn Owls (Tyto alba)
      collected from two regions with a contrasting degree of urbanisation and vicinity
      to point sources (Flanders in Belgium versus Normandy in France). Both tissues
      (muscle, liver, adipose and preen gland) and feathers (primary, tail and body
      feathers) showed elevated HBCD concentrations in Flanders, close to Europe's sole
      HBCD production plant in the Netherlands, and identified Normandy as a historical
      source region for PBDEs. In sharp contrast, the reactive BFR TBBPA bioaccumulated
      poorly (2.3%) in tissue samples, but was present in 96% of all body feather
      samples (0.36-7.07ngg(-1)dw), equally in both regions. PBDE concentrations in
      tissues (7.46-903 ng g(-1)lw) were considerably lower in the investigated Flemish
      Barn Owls, collected in 2008/2009, compared to specimens collected in 2003/2004
      (46-11,000 ng g(-1)lw), possibly suggesting the effectiveness of the 2004
      European ban of Penta- and Octa-BDE mixtures. Feathers showed a similar trend and
      additionally exhibited HBCD concentrations (0.02-333 ng g(-1)dw) surpassing those
      of PBDEs (0.50-10.4 ng g(-1)dw). While body feathers were a reliable matrix to
      predict both internal PBDE (0.21 <= R(2)<= 0.67) and HBCD body burdens (0.20 <=
      R(2) <= 0.37), the suitability of primary and tail feathers appeared to be
      confounded by external contamination and moult. In conclusion, the present study
      clearly showed that the reactive versus additive use of BFRs results in
      contrasting exposure scenarios in a species higher up the food chain, and
      therefore may have profound implications for environmental health. In addition,
      the presented results extend the promising use of feathers as a non-destructive
      sampling strategy for current-use BFRs, and show that birds of prey are valid
      early-warning systems for environmental contamination.

PMID- 24300458
TI  - The prediction of PAHs bioavailability in soils using chemical methods: state of
      the art and future challenges.
AB  - The evaluation of the available fraction of hydrophobic organic contaminants
      (HOCs) is extremely important for assessing their risk to the environment and
      human health. This available fraction, which can be solubilized and/or easily
      extracted, is believed to be the most accessible for bioaccumulation, biosorption
      and/or transformation by organisms. Based on this, two main types of chemical
      methods have been developed, closely related to the concepts of bioaccessibility
      and freely available concentrations: non-exhaustive extractions and biomimetic
      methods. Since bioavailability is species and compound specific, this work
      focused only in one of the most widespread group of HOCs in soils: polycyclic
      aromatic hydrocarbons (PAHs). This study aims at producing a state of the art
      knowledge base on bioavailability and chemical availability of PAHs in soils,
      clarifying which chemical methods can provide a better prediction of an organism
      exposure, and which are the most promising ones. Therefore, a review of the
      processes involved on PAHs availability to microorganisms, earthworms and plants
      was performed and the outputs given by the different chemical methods were
      evaluated. The suitability of chemical methods to predict bioavailability of the
      16 US EPA PAHs in dissimilar naturally contaminated soils was not yet
      demonstrated, being especially difficult for high molecular weight compounds.
      Even though the potential to predict microbial mineralization using non
      exhaustive extractions is promising, it will be very difficult to achieve for
      earthworms and plants, due to the complexity of accumulation mechanisms which are
      not taken into account by chemical methods. Yet, the existing models could be
      improved by determining compound, species and site specific parameters. Moreover,
      chemical availability can be very useful to understand the bioavailability
      processes and the behavior of PAHs in soils. The inclusion of chemical methods on
      risk assessment has been suggested and it is promising, despite some methods
      overpredict risks. 

PMID- 24300459
TI  - A methodology for estimating risks associated with landslides of contaminated
      soil into rivers.
AB  - Urban areas adjacent to surface water are exposed to soil movements such as
      erosion and slope failures (landslides). A landslide is a potential mechanism for
      mobilisation and spreading of pollutants. This mechanism is in general not
      included in environmental risk assessments for contaminated sites, and the
      consequences associated with contamination in the soil are typically not
      considered in landslide risk assessments. This study suggests a methodology to
      estimate the environmental risks associated with landslides in contaminated sites
      adjacent to rivers. The methodology is probabilistic and allows for datasets with
      large uncertainties and the use of expert judgements, providing quantitative
      estimates of probabilities for defined failures. The approach is illustrated by a
      case study along the river Gota Alv, Sweden, where failures are defined and
      probabilities for those failures are estimated. Failures are defined from a
      pollution perspective and in terms of exceeding environmental quality standards
      (EQSs) and acceptable contaminant loads. Models are then suggested to estimate
      probabilities of these failures. A landslide analysis is carried out to assess
      landslide probabilities based on data from a recent landslide risk classification
      study along the river Gota Alv. The suggested methodology is meant to be a
      supplement to either landslide risk assessment (LRA) or environmental risk
      assessment (ERA), providing quantitative estimates of the risks associated with
      landslide in contaminated sites. The proposed methodology can also act as a basis
      for communication and discussion, thereby contributing to intersectoral
      management solutions. From the case study it was found that the defined failures
      are governed primarily by the probability of a landslide occurring. The overall
      probabilities for failure are low; however, if a landslide occurs the
      probabilities of exceeding EQS are high and the probability of having at least a
      10% increase in the contamination load within one year is also high. 

PMID- 24300461
TI  - Epigenetics of chronic pain after thoracic surgery.
AB  - PURPOSE OF REVIEW: Chronic pain after surgery is a major public health problem
      and a major concern for perioperative physicians. Thoracic surgery presents a
      unique challenge, as thoracotomy is among the highest risk surgeries to develop
      persistent postsurgical pain. The purpose of this review is to discuss the
      relevance of research in pain epigenetics to patients with persistent pain after
      thoracic surgery. RECENT FINDINGS: Recent advances have linked chronic pain
      states to genetic and epigenetic changes. Progress in our understanding of
      chronic pain has highlighted the importance of immune modulation of pain. It is
      possible that epigenetic changes driving chronic pain occur in the perioperative
      setting via histone modification and DNA methylation. SUMMARY: The transition
      from acute to chronic pain after thoracic surgery may be mediated by epigenetics.
      Here, we discuss epigenetic modifications that have been discovered in animal
      models of chronic pain that may predispose patients to persistent neuropathic
      pain after thoracic surgery.

PMID- 24300462
TI  - Cerebral protection: inflammation, endothelial dysfunction, and postoperative
      cognitive dysfunction.
AB  - PURPOSE OF REVIEW: Postoperative cognitive dysfunction (POCD) is a well
      recognized perioperative syndrome, with approximately 15% of patients over the
      age of 60 years displaying objectively measured decrease in cognitive function as
      a consequence of anesthesia and surgery. The exact cause, however, remains
      unknown. This review aims to update anesthesiologists on the recent advancements
      in the understanding of the pathophysiology of POCD. RECENT FINDINGS: Recent
      evidence suggests that the observed predilection to POCD is likely mediated by a
      neuro-inflammatory response - with surgery being a major contributing factor. The
      blood-brain barrier, a highly specialized endothelial layer, is exquisitely
      sensitive to an inflammatory insult and implicated in the cause of other
      neurocognitive syndromes also characterized by neuro-inflammation such as
      cerebral malaria. Inflammatory changes may disrupt the blood-brain barrier and
      facilitate migration of macrophages into the brain, damaging synapses and
      neurones and ultimately lead to POCD. This review explores the important question
      of causality - the potential relationship between inflammation, endothelial
      dysfunction, and postoperative cognitive decline. SUMMARY: Recent research points
      to a central role of a neuro-inflammatory cascade in POCD, with endothelial
      dysfunction potentially aggravating the insult. Investigating the genomic and
      molecular mechanisms that underlie the intervariation in the inflammatory
      response to surgery, improving the identification of appropriate endothelial and
      inflammatory biomarkers, and developing endothelial modulatory and anti
      inflammatory (prevention and resolution) strategies are key areas of future
      translational research. This is important as the elderly, who show increased
      susceptibility to this and other perioperative illness syndromes, represent an
      ever-increasing proportion of patients presenting for surgery.

PMID- 24300460
TI  - Concentrations of persistent organic pollutants (POPs) in human blood samples
      from Mexico City, Mexico.
AB  - Studies in Mexico have demonstrated exposure to persistent organic pollutants
      (POPs) in people living in different sites through the country. However, studies
      evaluating exposure to POPs in people living in Mexico City (one of most
      contaminated places in the world) are scarce. Therefore, the aim of this study
      was to assess the levels of polybrominated diphenyl ethers (PBDEs),
      polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its
      metabolite dichlorodiphenyldichloroethylene (DDE) in the blood as exposure
      biomarkers in people living in Mexico City. A total of 123 participants (blood
      donors aged 20-60 years) were recruited during 2010 in Mexico City. Quantitative
      analyses of blood samples were performed using gas chromatography coupled with
      mass spectrometry. Levels of the assessed compounds ranged from non-detectable
      (<LOD) to 350 ng/g lipid; from 8.20 to 91.0 ng/g lipid and from <LOD to 34.0 ng/g
      lipid for total PBDEs, total PCBs and total DDT, respectively. The current study
      indicates POP exposure in the people assessed and highlights the need for further
      biomonitoring studies of these POPs in the region. In this regard, biomonitoring
      of toxins on a global scale may be the first step towards the prevention of toxin
      induced illnesses in the population.

PMID- 24300463
TI  - Role of alpha1 adrenergic antagonism in the mechanism of action of iloperidone:
      reducing extrapyramidal symptoms.
AB  - ISSUE: The low incidence of extrapyramidal side effects associated with the
      atypical antipsychotic iloperidone may be linked to its unique binding profile of
      high affinity antagonism of both alpha1 adrenergic receptors and serotonin 2A
      receptors.

PMID- 24300465
TI  - Fertility conserving management of early cervical cancer: our experience of LLETZ
      and pelvic lymph node dissection.
AB  - BACKGROUND: Presently, for those diagnosed with early cervical cancer who wish to
      conserve their fertility, there is the option of radical trachelectomy. Although
      successful, this procedure is associated with significant obstetric morbidity.
      The recurrence risk of early cervical cancer is low and in tumors measuring less
      than 2 cm; if the lymphatics are negative, the likelihood of parametrial
      involvement is less than 1%. Therefore, pelvic lymph nodes are a surrogate marker
      of parametrial involvement and radical excision of the parametrium can be omitted
      if they are negative. OBJECTIVE: The aim of this study was to report our
      experience of the fertility conserving management of early cervical cancer with
      repeat large loop excision of the transformation zone and laparoscopic pelvic
      lymph node dissection. METHODS: Between 2004 and 2011, a retrospective review of
      cases of early cervical cancer who had fertility conserving management within
      Glasgow Royal Infirmary was done. RESULTS: Forty-three patients underwent
      fertility conserving management of early cervical cancer. Forty were screen
      detected cancers; 2 were stage IA1, 4 were stage IA2, and 37 were stage IB1.
      There were 2 central recurrences during the follow-up period. There have been 15
      live children to 12 women and there are 4 ongoing pregnancies. CONCLUSIONS: To
      our knowledge, this is the largest case series described and confirms the low
      morbidity and mortality of this procedure. However, even within our highly select
      group, there have been 2 cases of central recurrent disease. We, therefore, are
      urging caution in the global adoption of this technique and would welcome a
      multicenter multinational randomized controlled trial.

PMID- 24300466
TI  - Synchronous ovarian and endometrial cancer--an international multicenter case
      control study.
AB  - OBJECTIVES: This study aimed to compare the prognosis of patients with
      synchronous endometrial and ovarian cancer (SEOC) to matched controls with either
      endometrial cancer (EC) or ovarian cancer (OC). METHODS: A retrospective case
      control study including all patients with SEOC who had been treated at 5 European
      tertiary gynecologic oncology centers between 1996 and 2011 and patients with
      either EC or OC matched for age, International Federation of Gynecology and
      Obstetrics (FIGO) stage, histology, year of diagnosis, and Eastern Cooperative
      Oncology Group performance score. RESULTS: The study cohort comprised 77, 132,
      and 126 patients with SEOC, EC, and OC, respectively. The patient characteristics
      confirmed an equal distribution of matching factors, and the median follow-up did
      not differ (P = 0.44). 48.1% of the patients with SEOC showed early FIGO stage I
      for both EC and OC. The 5-year PFS rates differed between SEOC and EC (76.3% vs
      86.3%; P = 0.047) but not the 5-year overall survival rates (71.6% vs 79.8%; P =
      0.12) and did not differ between SEOC and OC (76.3% vs 63.8%; P = 0.19 and 71.6%
      vs 69.3%; P = 0.61, respectively). After the adjustment for the FIGO stage of the
      2 components of SEOC, neither PFS nor overall survival rates were different.
      CONCLUSIONS: Prognosis of patients with SEOC tended to be the same in comparison
      with matched controls with either one EC or OC. Therefore, it could be considered
      that patients with SEOC may be eligible for clinical trials of the advanced tumor
      component if no additional therapy is indicated for the other component.

PMID- 24300467
TI  - Molecular portraits of heterogeneity related to cancer stem cells in human
      ovarian cancer.
AB  - PURPOSE: The aim of this study was to investigate molecular portraits of
      heterogeneity related to cancer stem cells (CSCs) in human ovarian cancer and to
      access the value in diagnosis and treatment. METHODS: Sixty specimens were
      collected in both cytoreductive and re-cytoreductive surgeries of 20 serous
      papillary ovarian adenocarcinoma cases. Expression density and distribution of 3
      CSC markers (CD44, CD133, and CD117) and 3 stemness proteins (Bmi1, Nestin, and
      Oct3/4) were analyzed by immunohistochemical staining. Pairwise comparisons were
      performed among their expression in primary, metastasis, and relapsing tumors.
      RESULTS: Some molecules presented different localization in 1 tissue, like CD133
      and CD117, and all but Oct3/4 expressed differentially in different specimens of
      1 case. Compared to primary or metastatic cancers, recurrent cancers show higher
      expression of CD133, CD117, and Bmi1, as well as higher histological grades.
      CONCLUSIONS: Our study indicated that there exist extratumoral and intratumoral
      heterogeneity in ovarian epithelial cancers related to CSCs. And this is worth
      further studying.

PMID- 24300468
TI  - American Society of Clinical Oncology 2013: summary of scientific advancements in
      gynecologic cancer.
AB  - The American Society of Clinical Oncology (ASCO) meeting was held in Chicago,
      Ill, from May 31, 2013, to June 4, 2013, and focused on "Building Bridges to
      Conquer Cancer." An estimated 25,500 oncology professionals, with a broad range
      of interests, attended the meeting. Cervical cancer, a gynecologic malignancy
      with a significant global burden, was prominently featured at this year's
      meeting. In a mark of exemplary scientific accomplishment within our specialty, 2
      of the 5 general session plenaries investigated advancements in cervical cancer
      care, extending from improved screening to treatment of metastatic disease. This
      was followed by the presentation of several important phase 2 and 3 clinical
      trials in the Gynecologic Oncology Tract, focusing on cervical, ovarian, uterine,
      and breast cancer, which will be discussed in this report. 

PMID- 24300469
TI  - Neuroblastoma presenting as persistent postprandial emesis in a neonate.
AB  - Early identification and treatment of neuroblastoma, the most common malignant
      solid tumor in infants, (Atkinson et al. AJR Am J Roentgenol. 1986;146:113-117;
      Nuchtern. Semin Pediatr Surg. 2006;15:10-16; Lanzkowsky. Manual of Pediatric
      Hematology and Oncology. 4th ed. Burlington, MA: Elsevier Academic Press;
      2005:530-547) can improve prognosis of this illness. Benign emesis as an initial
      presentation of infantile neuroblastoma is rare (Isaacs. Fetal Pediatr Pathol.
      2007;26:177-184). We report a case of a 17-day-old healthy male who presented to
      the emergency department with persistent, nonprojectile emesis after feedings. A
      diagnosis of nonresectable stage IV thoracoabdominal neuroblastoma with invasion
      to the spine was made. We concluded that oncological processes, such as
      neuroblastoma, should be included in the differential diagnosis of persistent
      emesis in the neonatal period. Emergency physicians may have the opportunity to
      detect neuroblastoma earlier by contemplating a broader differential diagnosis of
      a vomiting infant and initiating the appropriate workup in the emergency
      department. 

PMID- 24300470
TI  - Honeycomb gallbladder: a very rare cause of right upper quadrant pain.
AB  - Honeycomb gallbladder is a rare congenital malformation of the gallbladder. In
      some cases, it may be asymptomatic, whereas in others, it may lead to symptoms
      consistent with biliary colic even in the absence of cholelithiasis. We present
      the clinical and imaging findings of a case of a 10-year-old boy who was admitted
      to the emergency department with right upper quadrant pain. Ultrasonography and
      magnetic resonance imaging showed a honeycomb gallbladder. Honeycomb gallbladder
      is safely diagnosed with ultrasonography, which should be part of the
      investigation of patients with right upper quadrant pain in the emergency
      department. 

PMID- 24300471
TI  - Positive lidocaine toxicology screen after J-Tip for venipuncture.
AB  - Venipuncture is common in children, and topical anesthetics are often used to
      alleviate the pain of the procedure. The J-Tip (National Medical Products, Inc,
      Irvine, Calif) device has become popular as a rapid and effective means of
      delivering lidocaine noninvasively. We report a case of a positive lidocaine
      blood toxicology screen after the use of the J-Tip device in a child pre
      venipuncture. A repeat toxicology screen obtained 1 hour later by venipuncture
      without J-Tip use was negative. This report serves to remind clinicians that
      topical anesthetics may interfere with toxicology assays, leading to unreliable
      toxicology results. 

PMID- 24300472
TI  - Triage in the Tower of Babel: interpreter services for children in the
      prehospital setting.
AB  - Minority pediatric populations have higher rates of emergency medical services
      use than the general pediatric population, and prior studies have documented that
      limited-English proficiency patients are more likely to undergo invasive
      procedures, require more resources, and be admitted once they arrive in the
      emergency department. Furthermore, limited-English proficiency patients may be
      particularly vulnerable because of immigration or political concerns. In this
      case report, we describe an infant with breath-holding spells for whom a language
      barrier in the prehospital setting resulted in an escalation of care to the
      highest level of trauma team activation. This infant underwent unnecessary,
      costly, and harmful interventions because of a lack of interpreter services. In a
      discussion of the legal, ethical, and medical implications of this case, we
      conclude that further investigation into prehospital strategies for overcoming
      language barriers is required to provide optimal prehospital care for pediatric
      patients. 

PMID- 24300473
TI  - The pediatric headache that would not go away.
AB  - We describe the clinical presentation, radiographic findings, management, and
      outcome of a subdural empyema in a 14-year-old male with history of recent
      partially treated acute sinusitis. Subdural empyema is a rare but life
      threatening complication, usually following paranasal sinusitis, otitis media,
      mastoiditis, cranial surgery, a skull fracture, or from distant spread from sites
      such as a pulmonary infection. The initial evaluation should include a thorough
      history and physical examination, complete blood count, electrolytes, C-reactive
      protein, erythrocyte sedimentation rate, chest x-ray, urinalysis, and
      neuroimaging of the brain with intravenous contrast. If a subdural empyema is
      identified, then intravenous antibiotics should be initiated, and immediate
      neurosurgical consultation should be obtained to consider operative drainage. 

PMID- 24300474
TI  - Shake, rattle, and roll: an update on pediatric seizures.
AB  - Seizure is a common presenting complaint for patients in the pediatric emergency
      department (PED) setting. In some cases, protocols are in place on how to manage
      this group of patients, for example, a patient with a simple febrile seizure
      already back to baseline or a patient with known epilepsy already back to
      baseline. However, many scenarios present dilemmas for physicians in the PED,
      specifically patients with status epilepticus (SE). Unfortunately, there is not a
      national SE protocol, and hospital-specific guidelines may or may not exist.
      Current practices are constantly changing because new medications arise, and more
      information is gathered regarding existing medications and guidelines. Here we
      will review the basics about first-time afebrile seizures presenting to the PED
      and common treatments specific to seizure types. We will then review SE
      management basics and medical therapy, including both older and newer agents and
      their routes of administration for both the prehospital and the hospital setting.

PMID- 24300476
TI  - Pediatric emergency medicine: legal briefs.

PMID- 24300477
TI  - Partial hydatidiform mole and coexisting viable twin pregnancy.
AB  - Twin partial hydatidiform molar pregnancy with a viable fetus is an uncommon
      occurrence. Presentations of molar pregnancies include vaginal bleeding,
      unusually elevated beta-human chorionic gonadotropin level, and preeclampsia.
      Previous descriptions of twin molar and fetus pregnancies in the literature have
      been described in the outpatient obstetric setting. We present a case of partial
      molar pregnancy with a viable fetus detected with emergency ultrasound in a
      pediatric emergency department. 

PMID- 24300479
TI  - Detecting, visualizing and quantitating the generation of reactive oxygen species
      in an amoeba model system.
AB  - Reactive oxygen species (ROS) comprise a range of reactive and short-lived,
      oxygen-containing molecules, which are dynamically interconverted or eliminated
      either catalytically or spontaneously. Due to the short life spans of most ROS
      and the diversity of their sources and subcellular localizations, a complete
      picture can be obtained only by careful measurements using a combination of
      protocols. Here, we present a set of three different protocols using OxyBurst
      Green (OBG)-coated beads, or dihydroethidium (DHE) and Amplex UltraRed (AUR), to
      monitor qualitatively and quantitatively various ROS in professional phagocytes
      such as Dictyostelium. We optimised the beads coating procedures and used OBG
      coated beads and live microscopy to dynamically visualize intraphagosomal ROS
      generation at the single cell level. We identified lipopolysaccharide (LPS) from
      E. coli as a potent stimulator for ROS generation in Dictyostelium. In addition,
      we developed real time, medium-throughput assays using DHE and AUR to
      quantitatively measure intracellular superoxide and extracellular H2O2
      production, respectively. 

PMID- 24300481
TI  - Changes of glaciers in the Andes of Chile and priorities for future work.
AB  - Glaciers in the Andes of Chile seem to be shrinking and possibly loosing mass,
      but the number and types of studies conducted, constrained mainly by data
      availability, are not sufficient to provide a synopsis of glacier changes for the
      past or future or explain in an explicit way causes of the observed changes. In
      this paper, we provide a systematic review of changes in glaciers for the entire
      country, followed by a discussion of the studies that have provided evidence of
      such changes. We identify a missing type of work in distributed, physically
      oriented modelling studies that are needed to bridge the gap between the numerous
      remote sensing studies and the specific, point scale works focused on process
      understanding. We use an advanced mass balance model applied to one of the best
      monitored glaciers in the region to investigate four main research issues that
      should be addressed in modelling studies for a sound assessment of glacier
      changes: 1) the use of physically-based models of glacier ablation (energy
      balance models) versus more empirical models (enhanced temperature index
      approaches); 2) the importance of the correct extrapolation of air temperature
      forcing on glaciers and in high elevation areas and the large uncertainty in
      model outputs associated with it; 3) the role played by snow gravitational
      redistribution; and 4) the uncertainty associated with future climate scenarios.
      We quantify differences in model outputs associated with each of these choices,
      and conclude with suggestions for future work directions. 

PMID- 24300480
TI  - Autophagy-mediated regulation of macrophages and its applications for cancer.
AB  - Autophagy is a highly conserved homeostatic pathway that plays an important role
      in tumor development and progression by acting on cancer cells in a cell
      autonomous mechanism. However, the solid tumor is not an island, but rather an
      ensemble performance that includes nonmalignant stromal cells, such as
      macrophages. A growing body of evidence indicates that autophagy is a key
      component of the innate immune response. In this review, we discuss the role of
      autophagy in the control of macrophage production at different stages (including
      hematopoietic stem cell maintenance, monocyte/macrophage migration, and monocyte
      differentiation into macrophages) and polarization and discuss how modulating
      autophagy in tumor-associated macrophages (TAMs) may represent a promising
      strategy for limiting cancer growth and progression. 

PMID- 24300482
TI  - Towards finding a population biomarker for wastewater epidemiology studies.
AB  - Wastewater analysis has the potential to provide objective information on
      community drug use. Introducing a population biomarker (PB) in the sample
      analysis may significantly reduce errors in the back-calculation associated with
      population estimation and wastewater volume measurement. A number of potential
      PBs have been suggested but no systematic evaluation has been conducted so far.
      This study evaluated the eligibility of the previously suggested PB candidates
      (creatinine, cholesterol, coprostanol and cotinine) as well as three new ones
      (cortisol, androstenedione and 5-hydroxyindoleacetic acid (5-HIAA)) using five
      criteria. We assessed the quantification method, affinity to particulate matter
      and stability of candidates in wastewater, as well as the constancy of inter-day
      excretion and correlation between excretion and census population. All PB
      candidates were quantifiable in wastewater. Cholesterol and coprostanol were
      eliminated from further consideration due to affinity to particulate matters in
      the wastewater. Creatinine, cortisol and androstenedione were disqualified for
      stability reasons. On a population scale, both cotinine and 5-HIAA were excreted
      (RSD=8.01 +/- 1.13% and 10.20 +/- 0.89%, respectively) at a constant rate and
      concentrations of each correlated well with the census population (r=0.9809 and
      0.9442, respectively). Overall, both cotinine and 5-HIAA are eligible PBs, but
      the neurotransmitter metabolite 5-HIAA may be more suitable for international
      comparisons.

PMID- 24300483
TI  - Pathological T0 following radical cystectomy with or without neoadjuvant
      chemotherapy: a useful surrogate.
AB  - PURPOSE: Several large, randomized, controlled trials provide evidence that
      neoadjuvant chemotherapy improves the outcome of radical cystectomy for muscle
      invasive urothelial bladder cancer. We analyzed the designs, methods and
      observations of these trials to identify patient subgroups that appeared most
      likely to benefit. We also identified distinguishing features compared to groups
      that did not achieve improved outcomes. MATERIALS AND METHODS: We analyzed
      initial and updated methods and results of the 4 main prospective trials of
      neoadjuvant chemotherapy (SWOG, Medical Research Council, and Nordic I and II)
      and subsequent meta-analyses. These series are the basis for advocating
      neoadjuvant chemotherapy in all patients with muscle invasive urothelial bladder
      cancer who undergo radical cystectomy. RESULTS: The greatest apparent benefit was
      seen in patients free of cancer at radical cystectomy (pT0). They had markedly
      improved overall and disease specific survival compared to patients with residual
      disease. However, improvements occurred regardless of whether there was down
      staging from muscle invasive urothelial bladder cancer to pT0 after transurethral
      resection alone (controls) or after resection plus neoadjuvant chemotherapy.
      Thus, the major benefit of chemotherapy appeared to be that more patients
      achieved pT0. We also explored the study limitations that may have influenced
      outcomes and considered the potential for overtreatment in patients not likely to
      benefit from chemotherapy. Finally, we used risk stratification to create a
      decision tree model for selecting patients for neoadjuvant chemotherapy that
      could conceivably maximize oncologic outcome and minimize overtreatment.
      CONCLUSIONS: Patients with pT0 in the 4 main neoadjuvant chemotherapy trials and
      their subsequent meta-analyses experienced similar survival, far exceeding that
      in groups that did not achieve pT0. The benefit of neoadjuvant chemotherapy
      appears to be the larger number of cases than in the transurethral resection only
      group that were down-staged to pT0, suggesting that variables other than
      chemotherapy may have influenced outcomes. Therefore, strategies to selectively
      administer neoadjuvant chemotherapy to certain patients at risk have the
      potential to maintain improved bladder cancer outcomes while reducing
      overtreatment and its associated toxicity.

PMID- 24300485
TI  - [Role of proinflammatory cytokines in the development and progression of micro-
      and macroangiopathies in patients with type 2 diabetes mellitus].
AB  - Diabetes mellitus is a systemic lesion of the micro- and macrocirculatory bed. We
      examined a total of 110 people with type 2 diabetes mellitus and lesions of the
      major vessels of the lower limbs. Of these, 70 patients were found to have
      microangiopathy combined with nephropathy. Diabetic nephropathy was classified
      depending on the level of microalbuminuria and the glomerular filtration rate.
      All patients were subdivided into three groups: diabetic macroangiopathy of the
      lower extremities with neither diabetic nephropathy nor chronic renal disease,
      lower-limb diabetic macroangiopathy combined with diabetic nephropathy in stage 1
      of microalbuminuria of chronic renal disease and those in combination with
      diabetic nephropathy in stage 2 of microalbuminuria chronic renal disease. We
      measured the level of interleukine-6 and interleukine-8, tumour necrosis factor
      alpha, fibrinogen and the von Willebrand factor, revealing simultaneous
      progression of lower limb angiopathy in diabetic nephropathy, with direct
      interrelation between proinflammatory cytokines and the haemostasis system
      parameters. A decrease in the interleukine-8 level as nephropathy progresses may
      be indicative of exhaustion of angiogenesis, which is one of the factors of
      progression of macroangiopathy in patients with diabetes mellitus. 

PMID- 24300484
TI  - Practice patterns and resource utilization for infants with bladder exstrophy: a
      national perspective.
AB  - PURPOSE: Substantial variability exists in bladder exstrophy care, and little is
      known about costs associated with the condition. We define the care patterns and
      first year cost for patients with bladder exstrophy at select freestanding
      pediatric hospitals in the United States. MATERIALS AND METHODS: We used the
      Pediatric Health Information System database to identify patients with bladder
      exstrophy born between January 1999 and December 2010 who underwent primary
      closure in the first 120 days of life. Demographic, surgical, postoperative and
      cost data for all encounters were assessed. Multivariate linear regression was
      used to examine the association between patient, surgeon and hospital
      characteristics and costs. RESULTS: Of the 381 patients who underwent primary
      closure within the first 120 days of life 279 (73%) did so within the first 3
      days of life. A total of 119 patients (31%) underwent pelvic osteotomy, including
      51 of 279 (18%) who underwent closure within the first 3 days of life, 38 of 67
      (56%) who underwent closure between 4 and 30 days of life, and 30 of 35 (86%) who
      underwent closure between 31 and 120 days of life (p = 0.0017). Median inflation
      adjusted, first year cost in United States dollars per patient was $66,577 (IQR
      $45,335 to $102,398). Presence of nonrenal comorbidity and completion of primary
      closure after 30 days of life increased first year costs by 24% and 53%,
      respectively. Increased post-closure length of stay was associated with greater
      costs. CONCLUSIONS: At select freestanding United States pediatric hospitals the
      majority of bladder exstrophy closures are performed within the first 3 days of
      life. Most, but not all, patients undergoing closure after the neonatal period
      undergo osteotomy. The presence of nonrenal comorbidity and increased
      postoperative length of stay are associated with greater costs.

PMID- 24300486
TI  - [Comparative pharmacoeconomic analysis of prostanoids for peripheral arterial
      occlusive].
AB  - Peripheral arteries occlusive disease (PAOD) is a prevalent illness that needs
      improved pharmacological management, especially for patients not eligible for
      surgical revascularization. Prostanoids (alprostadil or iloprost) were shown to
      be effective in PAOD and critical limb ischemia (CLI) but are rather costly. The
      results of our pharmacoeconomic study (cost estimation based on randomized
      control trial results) showed that iloprost does not increase cost of treatment
      when only direct medical costs are taken into account. If indirect costs are
      included into the analysis iloprost saves up to 27 thousand rubles per patient.
      Clinical efficacy is still high. Thus iloprost is a better alternative than
      alprostadil for CLI. 

PMID- 24300487
TI  - [Endothelium-dependent factors of pathogenesis of a relapse of varicose disease:
      a diagnostic concept and treatment policy].
AB  - A relapse of lower-limb varicose disease (LLVD), despite the development of
      surgical achievements in surgical technologies is currently an important problem
      of present-day phlebology. A considerable factor of its pathogenesis is
      endothelial dysfunction (ED). The results of clinical studies of "false" relapses
      (n=32) and the control group were indicative of pronounced ED. Studying the level
      of leukocytes confirmed a hypothesis on a "leukocytic" trap at the level of the
      varicose veins of lower extremities. The authors analysed the dynamics of certain
      markers of ED (CECs, VCAM-1, P-selectin, E-selectin t-RA, endothelin-1),
      suggestive of the degree of ED severity, revealing a tendency towards
      normalization of the ED markers on the background of phlebotrophic therapy
      (Antistax). The carried out study also makes it possible to conclude that the
      level of endothelemia and biochemical indices of ED may serve as an evaluating
      marker of the activity of processes of varicose transformation of veins in
      patients with a relapse of the disease. 

PMID- 24300488
TI  - [State of kinin regulation and endothelial function in patients with ischaemic
      stroke].
AB  - The study was aimed at assessing the degree of impairments of the kinin
      mechanisms by the level of antibodies to bradykinin in patients with ischaemic
      stroke in association with the indices of the vascular endothelium function. We
      examined people belonging to four various categories, i.e. 30 apparently healthy
      people (the control group), 30 high-risk patients with degree I-II arterial
      hypertension, 56 patients with degree II-III arterial hypertension running very
      high risk for cardiovascular disease, and 35 patients undergoing in-hospital
      treatment for acute stage of ischaemic stroke. We determined the content of
      natural antibodies to bradykinin (NABB) and the indices of endothelial function.
      We revealed alterations in the content of NABB in all groups of patients as
      compared with the control group. Their degree depended upon the disease and was
      highest in patients with stroke. Simultaneously we revealed impaired functioning
      of the vascular endothelium, the key manifestation of which was a pronounced
      decrease in the endothelium-dependent vasodilation in patients with stroke.
      Despite different directivity of alterations of certain indices of endothelial
      function in the groups of patients, we revealed statistically significant
      correlations of the alterations with the content of NABB. 

PMID- 24300489
TI  - [Biochemical and morphological assessment of the functional state of the
      endothelium in reconstructive operations on the abdominal aorta in animal
      experiments].
AB  - The article deals with the analysis of biochemical and morphological alterations
      in the functional state of the endothelium of laboratory animals after a
      reconstructive surgical intervention on the abdominal aorta. These alterations
      were assessed at various terms following operative treatment in the comparison
      group and intact control group. The authors carried out of computer-assisted
      morphometry of the reconstruction zone on histological preparations for correct
      interpretation of the biochemical alterations and assessment of the correlation
      between the studied biochemical indices in blood and the arterial wall. 

PMID- 24300490
TI  - [Possibilities of instrumental methods of diagnosis of unstable atherosclerotic
      plaques of carotid arteries].
AB  - Today there exists a wide variety of laboratory and instrumental methods aimed at
      diagnosing an unstable carotid aortosclerotic plaque. Assessment of the
      laboratory indices is not sufficiently effective since it does not allow of
      revealing the fact of the formation of an unstable plague at early stages and to
      determine its localization. The instrumental methods employed (ultrasonographic
      study, magnetic resonance imaging, multiplanar computed tomography, positron
      emission tomography) were focussed on detecting pathomorphological markers of
      instability - thickness of the fibrous coating, structural plaques, the presence
      of erosions, ulcerations, haemorrhages, calcifications, lipid nucleus, activity
      of the cellular processes inside the plaque. The revealed signs promote early
      diagnosis of unstable atherosclerotic plaque with the determination of its
      localization. Nevertheless, they do not provide evidence about the danger of its
      rupture, whereas the overwhelming majority of acute vascular catastrophes
      including acute impairments of cerebral circulation is directly associated with
      arterial thrombosis resulting from rupture of the atherosclerotic plaque.
      Therefore, search for new methods aimed at prediction of complications of the
      atherosclerotic plaque which would be employed in routine clinical practice still
      remain urgently important today. The most promising is the study of the state of
      the atherosclerotic plaques of carotid arteries for prediction of acute
      impairment of cerebral circulation. 

PMID- 24300491
TI  - [State of the lower-limb lymphatic bed after open and endoscopic exposure of the
      great saphenous vein during coronary artery bypass grafting].
AB  - The article deals with the results of a comparative analysis of the state of the
      lower-limb lymphatic bed depending on the method of exposing the great saphenous
      vein (GSV) during the operation of coronary artery bypass grafting (CABA).
      Pronounced lesions of the lower-limb lymphatic system after surgical aggression
      provoke the development of complication such as lymphorrhea, lymphocele, and
      secondary oedema. The chosen objective method of assessment was radionuclide
      lymphoscintigraphy allowing of dynamically evaluating the alterations in the
      lymphatic system. We examined a total of 205 patients presenting with coronary
      artery disease and subjected to CABA. The patients were subdivided into two
      groups depending on the method used to expose the vein, including 109 patients
      with endoscopic exposure of the vein and group two consisting of 96 patients
      undergoing open exposure of the vein. Lymphoscintigraphy was performed in 18
      patients with open exposure of the vein and in 23 patients with endoscopic
      exposure before and after the operation. Analysing the obtained findings revealed
      that according to the results of lymphoscintigraphy endoscopic exposure of the
      GSV was accompanied predominantly by an insignificant degree of impairment of the
      lymphatic drainage in 34.4%, whereas 94.4% were found to have mainly moderate-to
      severe impairments. The lymphatic complications rate in the group with open
      exposure of the GSV was considerably higher which was mainly associated with the
      development of early oedema confirmed by an increased volume of the lower third
      of the crus of the operated limb. Radionuclide lymphoscintigraphy may be
      recommended as a method of early preclinical diagnosis of impairments of lower
      limb lymphatic drainage in patients after exposure of the GSV in order to predict
      the development of clinically significant complications. 

PMID- 24300492
TI  - [Optimization of policy aimed at forming a permanent access based on
      ultrasonographic duplex scanning for programmed dialysis].
AB  - The study was aimed at optimizing the policy of forming a permanent vascular
      access (PVA) by means of preoperative colour duplex scanning (CDS) of vessels in
      patients on programmed haemodialysis. The study included 420 patients undergoing
      from September 2003 to September 2011 a total of 595 PVAs. The Study Group (Group
      I) patients (351 PVAs) were subjected to preoperative PVA of vessels of limbs
      accompanied by assessing velocity parameters of the venous blood flow. The
      comparison group (Group II) patients (244 PVAs) underwent clinical examination
      only. The end point of the study was early diagnosis of incompetence of the PVA.
      Using preoperative PVA of vessels improved the outcomes of forming the PVA,
      significantly increasing the number of native arteriovenous fistulas (AVF) as a
      whole: (88.0% for Group I and 65.6% for Group II; p<0.01), their variants: radial
      cephalic (I - 57.5%, II - 32.2%; p<0.01) and secondary radial-cephalic variants
      (I - 8.3%, II - 3.7%; p<0.01), leading to decreased frequency of using synthetic
      prostheses both totally (I - 12.0%, II - 34.4%; p<0.01) and in all positions
      (p<0.01) taken apart. Also decreased the frequency of the development of
      incompetence of all PVAs (I - 10.8%, II - 29.9%; p<0.01), AVFs as a whole (I -
      7.4%, II - 18.0%; p<0.01) and accesses with a synthetic prosthesis both as a
      whole (I - 1.7%, II - 11.9%; p<0.01) and in all positions separately (p<0.01).
      Determining the velocity parameters of venous blood flow made it possible to
      exclude the development of significant proximal venous obstruction and to refuse
      phlebography. We consider it obligatory to perform CDS of vessels prior to
      forming a PVA. 

PMID- 24300493
TI  - [Results of assessing the distance from the valve of the introducer inserted into
      either the right or left radial artery to the aortic bifurcation by means of an
      angiographic catheter].
AB  - AIM: The study was aimed at determining the length of the angiographic catheter
      connecting either the left or right radial access with the aortic bifurcation and
      at analysing the relationship between this distance and simple anthropometric
      parameters. METHODS AND RESULTS: The study included a total of ninety-eight
      patients admitted to the Regional Clinical Hospital for performing elective
      invasive angiography of the lower extremities through a radial approach. In 47%
      (46/98) of cases the left radial artery was punctured and in 53% (52/98) of cases
      the right one. The average value of the catheter's length from the introducer's
      valve to the aortic bifurcation for the whole sample amounted to 111,5 cm (95%
      confidence interval 110,3-112,7 cm). We also determined several anthropometric
      parameters: "patient's height", "shoulder height in the sitting position", and
      "span of the arms". None of the parameters measured showed statistically
      significant differences in the groups of patients punctioned either into the
      right or left radial artery (p>0,05), including the measure "catheter's length".
      We revealed a significantly strong linear correlation between the measures
      "catheter's length" and "patient's height", correlation coefficient r=0,71
      (p<0,0001), between the parameters "catheter's length" and "span of the arms"
      r=0,71 (p<0,0001). We made an equation of regression (R-Squire 0,56): "catheter's
      length" = 24 + 0.28 * "patient's height" + 0,3 * "span of the arms". CONCLUSION:
      The carried out analysis demonstrated no statistically significant differences in
      the length of the catheter connecting either the left or right radial artery with
      the aortic bifurcation. Also suggested herein is a model for predicting the
      values of the catheter's length from the radial approach to the aortic
      bifurcation for patients with obliterating atherosclerosis of lower limbs, based
      on simple anthropometric measures "patient's height" and "span of the arms".

PMID- 24300494
TI  - [Peculiarities of treatment for pulmonary embolism (PE) in haematogenic
      thrombophilia].
AB  - The article deals with the results of examination and treatment of 70 patients
      presenting with acute pulmonary embolism (PE). The incidence of haematogenic
      thrombophilia in the examined patients amounted to 25.7%. The patients with
      haematogenic thrombophilia were found to have thromboses and embolisms in the
      cava filter more often than patients with unknown-aetiology pulmonary embolism.
      It was proved that differentiated therapy for haematogenic thrombophilia can
      significantly reduce the risk of recurrent thrombotic episodes in patients with
      acute pulmonary embolism. 

PMID- 24300495
TI  - [Symptomatology and diagnosis of inferior vena cava dysplasias].
AB  - The authors analysed the results of examination and dynamic follow up (from 2003
      to 2011) of twenty-one 15-to-55-year-old male patients presenting with hypoplasia
      or aplasia of the inferior vena cava. The diagnosis was verified by means of SCT-
      or MRT-phlebography. The disease was newly diagnosed at the age of 15-55 years
      (mean 25.9+/-2.6). The pathology manifested itself as a clinical course of
      thrombosis of deep veins of lower limbs in 16 (76.2%) patients and by oedema
      thereof in 5 (23.8%) subjects. Of the 16 patients with symptomatology of deep
      vein thrombosis, 13 patients had proximal (iliofemoral) thrombosis and 3 patients
      had distal thrombosis. In the overwhelming majority of the patients, the
      pathological process was localized on the right. All the patients after 1.5-12
      months developed signs of impaired patency of the IVC. 1.5-2.5 years later, the
      course of chronic venous insufficiency was complicated by the development of
      trophic ulcers of the crus in eight (38.1%) patients. Congenital abnormalities of
      the IVC are encountered predominantly in males, remaining for a long time latent
      to be newly manifested in the young age by symptoms of deep vein thrombosis (more
      often by right-sided iliac-femoral thrombosis). Suspecting this pathology should
      be followed by extended examination using SCT- or MRT-phlebography.

PMID- 24300496
TI  - [Efficacy of compression knee-high socks ULCER X in treatment of venous-genesis
      trophic ulcers].
AB  - The study was aimed at comparatively assessing the efficacy of treatment for
      venous trophic ulcers at stages II-III of the wound process using special
      compression knee-length socks of the ULCER X kit (Sigvaris AG, St. Gallen,
      Switzerland) and long-stretch bandages Lauma. Compression therapy was included
      into the programme of outpatient treatment of forty 31-to-74-year-old patients
      presenting with trophic ulcers (stage II-III of the wound process) with an
      average area of 5,36+/-1,1 cm2. The Study Group consisting of 20 patients used
      compression knitted fabrics in the form of knee-length socks ULCER X and the
      comparison group (n=20) used long-stretch bandages Lauma. RESULTS: The obtained
      findings (6 months) demonstrated that using compression therapy exerted a
      positive effect on the process of healing of venous trophic ulcers, also proving
      advantages of compression therapy with the knee-length socks ULCER X that create
      an adequate level of pressure on the crus and maintain it in long-term daily use,
      reliably accelerating the healing of venous trophic ulcers as compared with
      elastic long-stretch bandages. The use of long-stretch elastic bandages in
      treatment of venous trophic ulcers turned out to be not only ineffective but
      fraught with a possibility of the development of various complications. During 6
      months of follow up the patients using the special knee-length socks ULCER X were
      found to have 80 % of ulcers healed (16 patients), mainly within the first 2
      months, whereas using elastic bandages resulted in only 30 % of healing (6
      patients) by the end of the study. Along with it, we documented a considerable
      decrease in the malleolar circumference in the study group patients (from 30,05+/
      0,78 to 28,35+/-0,86 cm) and in the control group from 31,2+/-30,35 to 30,25+/
      0,75 cm), accompanied and followed by more than a two-fold increase in quality of
      life of the patients along all the parameters in the study group and a 1.4-fold
      increase in the control group patients.

PMID- 24300497
TI  - [Effect of the form of pathological tortuosity of the internal carotid artery on
      cerebral haemodynamics].
AB  - The prevalence of pathological tortuosity of carotid arteries according to the
      findings of angiographic studies varies from 10% to 43%. This pathology is
      morphologically diversified, requiring detailed verification of its forms in
      order to specify the character of impaired cerebral haemodynamics in each
      individual case. All patients presenting with manifestations of cerebral
      insufficiency underwent ultrasonographic duplex scanning of the vessels of the
      system of the brachiocephalic arteries according to the standard methods,
      measuring the volumetric velocity of blood flow before and after the pathological
      bend, the blood-flow linear velocity gradient. Revealing haemodynamically
      significant alterations was followed by contrast-enhanced computed tomography
      with subsequent 3-D reconstruction based on which we selected an optimal
      projection making it possible to measure the angles of the pathological bends.
      The second stage of the study consisted in mathematical calculations of the
      haemodynamic indices (the Reinolds number allowing of determining the regimen of
      the blood flow along the vessels, local losses of head according to the Weisbach
      formula, loss of pressure for local resistance), and statistical treatment of the
      data (two-tailed exact Fisher's test, Statistica 6.0). The obtained findings
      suggest a statistically significant increase in the prevalence of ischaemic
      stroke in patients with the angle of the pathological bend measuring 60 degrees 
      and less. Patients of this group are found to have an increase in the linear
      velocity of blood flow exceeding 150 cm/s and the value of the gradient over 2.4,
      thus suggesting haemodynamic significance. An increase in the acuity of the angle
      of a smooth turn from 60 degrees  to 30 degrees  was accompanied by a 3-fold
      increase in loss of pressure on the portion of local resistance from 509 to 1,466
      Pa. Thus, in the vessels with the angle of a smooth turn of 90 degrees  and more
      haemodynamic alterations to a large extent depend on the internal surface of the
      vascular wall, in the bends of the vessel with a turning angle of less than 90
      degrees  they depend on the value of the angle of a smooth turn. 

PMID- 24300498
TI  - [Comparative study of the results of using stagewise open interventions and
      single-step hybrid operations in patients with coronary artery disease
      accompanied by lesions of carotid arteries].
AB  - The authors describe herein the technique of a hybrid single-stage intervention
      performed in patients presenting with coronary artery disease (CAD) combined with
      carotid artery atherosclerosis, as well as comparing the outcomes of using
      similar operations with the results of stagewise open interventions within a 30
      day postoperative period. High risk for the development of severe and not
      uncommonly fatal complications both in the carotid basin and coronary bed
      determines difficulty of therapeutic decision-making regarding this patient
      cohort. This problem has been the subject of study and discussion in both Russian
      and foreign literature for more than two decades. However, none of the currently
      existing techniques has yet been accepted as an optimal one. The hybrid approach
      is a relatively novel technique, with the number of publications describing its
      application being only sporadic. The present article demonstrates significantly
      better immediate results of using the hybrid technique, thus suggesting that it
      may well be considered as an alternative to the classical approaches, requiring
      however further studies. 

PMID- 24300499
TI  - [Correction of consumption coagulopathy in patients during open operations on the
      abdominal aorta].
AB  - The article deals with the results of studying the peculiarities of plasma
      thrombocytic haemostasis in patients undergoing operations on the abdominal
      portion of the aorta. A total of 96 patients were included into the study. All
      patients underwent open aorto-iliac reconstructions. Of these, 32 patients were
      operated on for an aneurysm of the infrarenal portion of the aorta, and 64
      patients for Leriche syndrome after having developed chronic critical ischaemia
      of the limbs. It was confirmed that consumption coagulopathy, better known as
      disseminated intravascular coagulation (DIC), had already been present in all
      those patients as early as at the preoperative stage. The authors worked out an
      algorithm of infusion-transfusion therapy in surgery of the infrarenal portion of
      the aorta. 

PMID- 24300500
TI  - [Upper thoracic sympathectomy in treatment of upper limb ischaemia in distal
      lesions of the arterial bed].
AB  - Analysed herein was efficacy of 76 videothoracoscopic upper chest sympathectomies
      performed for upper limb ischaemia in a total of 61 patients. Of these, 15
      patients were found to suffer bilateral lesions. The findings of clinical follow
      up and instrumental examinations (laser Doppler flowmetry, rheovasography,
      measuring transcranial oxygen tension in tissues) made it possible to draw a
      conclusion on efficacy of upper chest sympathectomy in distal lesions of the
      vascular bed of the upper extremities. 

PMID- 24300501
TI  - [Metabolic and genetic predictors of restenosis and thrombosis of arterial
      bioprostheses in the femoropopliteal position].
AB  - The present study was aimed at analysing the role of certain cytokines in the
      development of restenosis and thrombosis of biological prostheses
      "KemAngioprosthesis", as well as assessing the effect of polymorphic variants of
      genes on expression of pro- and anti-inflammatory interleukins. Group One (n=52)
      was composed of patients with an unfavourable outcome (prosthesis restenosis,
      accompanied by thrombosis in 35 patients). Group Two (n=59) comprised patients
      with functioning and unaltered prostheses. Group One patients were found to have
      a significantly higher level of the marker of chronic inflammation IgG and IL-8,
      amounting respectively to 22.43+/-0.75 mg/ml and to 6.34+/-1.008 pg/ml and
      16.35+/-0.84 mg/ml (p=0.01) and 3.96+/-0.399 pg/ml (p=0.01) in Group Two
      patients. Analysing the effect of polymorphic variants of genes on expression of
      pro- and anti-inflammatory interleukins showed that polymorphism of genes of
      proinflammatory cytokines (TNFalpha, IL-8 and IL-6) is high producing and
      polymorphism of the gene of anti-inflammatory cytokine IL-10 is low producing.
      Besides, we noted a clear-cut tendency toward higher incidence of polymorphic
      alleles of genes of proinflammatory cytokines in Group One patients. 

PMID- 24300502
TI  - [Objectivization of the choice of the amputation level in patients with lower
      limb critical ischaemia].
AB  - The authors compared the informative value of the intraoperative criteria for
      assessing viability of muscles in high amputations of limbs for chronic critical
      ischaemia. It was revealed that such signs as subjectively evaluated bleeding,
      contractility and oedema of muscles possess low specificity in relation to the
      development of early postoperative complications. Intraoperative macroscopic
      histochemical study (IHCS) of the activity of muscular tissue lactate
      dehydrogenase at the level of amputation showed sensitivity of 96,3% and
      specificity of 92,9 %. Taking into consideration the results of IHCS for
      objectivization of the choice of the level of amputation made it possible to save
      the knee joint in 8,9 % of patients with gangrene on the background of high
      occlusion of lower limb arteries and to decrease the frequency of postoperative
      necrosis of muscle of the stump from 15,0% to 3,5%. 

PMID- 24300503
TI  - [Endovascular treatment of posttraumatic arteriovenous fistulas of the subclavian
      artery].
AB  - The authors describe the use of different methods of endovascular treatment of
      patients with presenting with posttraumatic arteriovenous fistulas in the first
      segment of the subclavian artery exemplified by two clinical cases. The first
      case report concerns a patient having developed was an arteriovenous fistula
      after catheterization of the jugular vein. The arteriovenous aneurysm was
      occluded by means of embolizing spirals. In the second case report is patient
      having developed an arteriovenous fistula after a stab-and-slash wound in the
      area of the sternoclavicular junction. Long-term existence of the arteriovenous
      fistula was complicated by severe right-ventricular insufficiency. The
      arteriovenous fistula was separated by means of endoprosthetic repair of the
      first segment of the subclavian artery. These case reports demonstrate
      possibilities of roentgenovascular methods of treatment making it possible to
      successfully replace a technically complicated, traumatic surgical intervention
      for false arteriovenous aneurysms. 

PMID- 24300504
TI  - [Physical trainings in peripheral atherosclerosis: problems and ways of
      solution].
AB  - Physical trainings (PT) in patients with peripheral atherosclerosis (PA) improve
      quality of life and the prognosis. They are accompanied and followed by
      favourable shifts in metabolism of peripheral tissues. The currently existing
      guidelines are unequivocally in favour of the necessity of physical trainings in
      patients with signs of intermittent claudication (class I, level A evidence).
      However, there is a considerable gap between efficacy of regular physical
      exercises and readiness of patients to participate in them, with only a sparse
      number of patients with PA actually performing these programmes. The review gives
      a detailed consideration of both subjective and objective factors limiting the
      participation of PA patients in PT programmes. New approaches for solving this
      problem have recently been proposed. In order to prevent the development of
      painful sensations during PT, they propose to use low-intensity loads, also
      performing training of other muscular groups, integral trainings, including those
      using electrostimulation of skeletal muscles. Mention should be made of the
      beginning of PT in patients with subclinical manifestations of PA, behavioural
      therapy in PA patients. Revealing early forms of PA and carrying out active
      rehabilitative measures are more convenient to be performed by physicians
      specializing in neurosurgery, thus requiring new organizational approaches. 

PMID- 24300505
TI  - Prehospital thrombolysis: a manual from Berlin.
AB  - In acute ischemic stroke, time from symptom onset to intervention is a decisive
      prognostic factor. In order to reduce this time, prehospital thrombolysis at the
      emergency site would be preferable. However, apart from neurological expertise
      and laboratory investigations a computed tomography (CT) scan is necessary to
      exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized
      ambulance equipped with a CT scanner and point-of-care laboratory was designed
      and constructed. Further, a new stroke identifying interview algorithm was
      developed and implemented in the Berlin emergency medical services. Since
      February 2011 the identification of suspected stroke in the dispatch center of
      the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke
      emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care
      and with additional training in emergency medicine, takes a neurological
      examination. If stroke is suspected a CT scan excludes intracranial hemorrhage.
      The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If
      coagulation status of the patient is normal and patient's medical history reveals
      no contraindication, prehospital thrombolysis is applied according to current
      guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA,
      alteplase, Actilyse). Thereafter patients are transported to the nearest hospital
      with a certified stroke unit for further treatment and assessment of
      strokeaetiology. After a pilot-phase, weeks were randomized into blocks either
      with or without STEMO care. Primary end-point of this study is time from alarm to
      the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can
      be reduced by at least 20 min compared to regular care. 

PMID- 24300507
TI  - Homodigital artery flap reconstruction for fingertip amputation: a comparative
      study of the oblique triangular neurovascular advancement flap and the reverse
      digital artery island flap.
AB  - This fingertip reconstruction study retrospectively compared sensory recovery and
      active range of motion outcomes in neurovascular island advancement and reverse
      digital artery island flaps. Seventeen oblique triangular flaps and 14 reverse
      digital artery island flaps were performed for nail bed level fingertip
      amputations (Ishikawa subzone II). There was no significant difference between
      the two procedures in the Semmes-Weinstein monofilament test and range of motion
      results. For static and moving two-point discrimination tests, however, those
      with a reverse digital artery island flap required a longer period for sensory
      recovery compared to those with an oblique triangular advancement flap. This
      trend equilibrated at 12 months after surgery showing no significant difference
      in both static and moving two-point discrimination tests between the procedures. 

PMID- 24300508
TI  - Enchondroma of the distal phalanx causing rupture of flexor digitorum profundus:
      successful fixation avoiding a pull-out suture.

PMID- 24300509
TI  - Embryology of familial (non-syndromic) brachydactyly of the hand.
AB  - Isolated familial non-syndromic brachydactyly is interesting from the
      embryological point of view because the phenotypes of isolated brachydactyly are
      frequently overlapping, yet they are caused by different gene mutations and the
      ring finger is frequently relatively preserved. We review the embryology of
      isolated familial brachydactyly with special attention to these two features. 

PMID- 24300510
TI  - Long-term outcome (20 to 33 years) of radial shortening osteotomy for Kienbock's
      lunatomalacia.
AB  - Radial shortening osteotomy (RSO) as treatment for Kienbock's disease usually
      improves patient symptoms for several years. Four small series have also shown
      that the effect may last for decades, but only two studies have used a patient
      based assessment. We examined 16 patients, with a mean age at operation of 32
      years, evaluating clinical and radiological results at a mean 25 (range 20 to 33)
      years after surgery. Three patients had progressive lunate collapse, of whom one
      patient needed a silicone implant arthroplasty 2 years after RSO and one patient
      a wrist fusion 16 years after RSO. The time between onset of symptoms and
      osteotomy in the remaining 14 patients averaged 20 months. The mean VAS for pain
      was 0.9 at rest, 0.9 with unloaded motion, 1.7 with slight, and 3.0 with heavy
      exertion. Two patients had marked wrist pain. Compared with the contralateral
      wrist the mean range of motion was 88%, grip strength was 95%, and key pinch
      107%. The Disabilities of the Arm, Shoulder, and Hand score averaged 6.1, and the
      Mayo wrist score, 79.3. The Lichtman stage remained unchanged in 56% of patients.
      The inner structure of the lunate improved in all patients, and its shape
      remained unchanged in half of the cases. Radial shortening osteotomy provides
      decade-long improvement in 75% of patients and seems to be a reasonable treatment
      for symptomatic Kienbock's disease. 

PMID- 24300511
TI  - Involvement of Carboxylesterase in Hydrolysis of Propranolol Prodrug during
      Permeation across Rat Skin.
AB  - The use of a prodrug, a conjugate of an active drug with a lipophilic
      substituent, is a good way of increasing the cutaneous absorption of a drug.
      However, the activity of dermal hydrolases has rarely been investigated in
      humans, or experimental animals. In the present study, we focused on the
      identification of rat dermal esterases and the hydrolysis of a prodrug during
      permeation across rat skin. We found that carboxylesterase (CES), especially the
      rat CES1 isozyme, Hydrolase A, is expressed in rat skin and that the hydrolysis
      of p-nitrophenyl acyl derivatives and caproyl-propranolol (PL) was 20-fold lower
      in the 9000g supernatant fraction of skin homogenate than in liver microsomes. A
      permeation study of caproyl-PL was performed in rat full-thickness and stripped
      skin using a flow-through diffusion cell. Caproyl-PL was easily partitioned into
      the stratum corneum and retained, not only in the stratum corneum, but also in
      viable epidermis and dermis. Caproyl-PL could barely be detected in the receptor
      fluid after application to either full-thickness or stripped skin. PL, derived
      from caproyl-PL, was, however, detected in receptor fluid after extensive
      hydrolysis of caproyl-PL in viable skin. Permeation of PL was markedly decreased
      under CES inhibition, indicating that the net flux of caproyl-PL is dependent on
      its conversion rate to PL. 

PMID- 24300512
TI  - Transdermal delivery of adriamycin to transplanted ehrlich ascites tumor in mice.
AB  - There is considerable interest in the skin as a site of anti-cancer drug
      application. Nevertheless, the skin poses a formidable barrier to drug
      penetration, thereby limiting topical and transdermal bioavailability. However,
      we previously showed that a thioglycolate-based depilatory agent increases the
      drug permeability of mouse skin. In the present report, we investigated the skin
      permeability and efficacy of the anti-cancer drug adriamycin increased when
      administered transdermally to mice in combination with a thioglycolate-based
      depilatory agent. Adriamycin in combination with depilatory treatment reduced
      Ehrlich tumor growth in hairless mice about the weight and size of harvested
      tumors. In addition, our delivery method for adriamycin increased the therapeutic
      effectiveness of this agent by decreasing toxicity. Moreover, measurement of
      adriamycin autofluorescence revealed that topically applied adriamycin penetrate
      the dermis after depilatory agent treatment. These results indicate that the
      transdermal delivery of anti-cancer drugs is feasible by handy pretreatment of
      the skin with a thioglycolate-based depilatory agent. 

PMID- 24300513
TI  - Adjuvant effect of cationic liposomes for subunit influenza vaccine: influence of
      antigen loading method, cholesterol and immune modulators.
AB  - Cationic liposomes are potential adjuvants for influenza vaccines. In a previous
      study we reported that among a panel of cationic liposomes loaded with influenza
      hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the
      strongest immune response. However, it is not clear whether the cholesterol
      (Chol) backbone or the tertiary amine head group of DC-Chol was responsible for
      this. Therefore, in the present work we studied the influence of Chol in the
      lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the
      HA loading method (adsorption versus encapsulation) and the encapsulation of
      immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes
      consisting of a neutral lipid (DPPC or Chol) and a cationic compound (DC-Chol,
      DDA, or eDPPC) were produced by film hydration-extrusion with/without an
      encapsulated immune modulator (CpG or imiquimod). The liposomes generally showed
      comparable size distribution, zeta potential and HA loading. In vitro studies
      with monocyte-derived human dendritic cells and immunization studies in C57Bl/6
      mice showed that: (1) liposome-adsorbed HA is more immunogenic than encapsulated
      HA; (2) the incorporation of Chol in the bilayer of cationic liposomes enhances
      their adjuvant effect; and (3) CpG loaded liposomes are more efficient at
      enhancing HA-specific humoral responses than plain liposomes or Alhydrogel. 

PMID- 24300514
TI  - New Transfection Agents Based on Liposomes Containing Biosurfactant MEL-A.
AB  - Nano vectors are useful tools to deliver foreign DNAs, oligonucleotides, and
      small interfering double-stranded RNAs (siRNAs) into mammalian cells with gene
      transfection and gene regulation. In such experiments we have found the liposomes
      with a biosurfacant mannosylerythriol lipid (MEL-A) are useful because of their
      high transfer efficiency, and their unique mechanism to transfer genes to target
      cells with the lowest toxicity. In the present review we will describe our
      current work, which may contribute to the great advance of gene transfer to
      target cells and gene regulations. For more than two decades, the liposome
      technologies have changed dramatically and various methods have been proposed in
      the fields of biochemistry, cell biology, biotechnology, and so on. In addition,
      they were towards to pharmaceutics and clinical applications. The liposome
      technologies were expected to use gene therapy, however, they have not reached a
      requested goal as of yet. In the present paper we would like to present an
      approach using a biosurfactant, MEL-A, which is a surface-active compound
      produced by microorganisms growing on water-insoluble substrates and increases
      efficiency in gene transfection. The present work shows new transfection agents
      based on liposomes containing biosurfactant MEL-A. 

PMID- 24300515
TI  - Physical and oxidative stability of uncoated and chitosan-coated liposomes
      containing grape seed extract.
AB  - Polyphenol-rich grape seed extract (0.1 w/w%) was incorporated in liposomes (1
      w/w% soy lecithin) by high pressure homogenization (22,500 psi) and coated with
      chitosan (0.1 w/w%). Primary liposomes and chitosan-coated secondary liposomes
      containing grape seed extract showed good physical stability during 98 days of
      storage. Most of the polyphenols were incorporated in the shell of the liposomes
      (85.4%), whereas only 7.6% of the polyphenols of grape seed extract were located
      in the interior of the liposomes. Coating with chitosan did not change the
      polyphenol content in the liposomes (86.6%). The uncoated liposomes without grape
      seed extract were highly prone to lipid oxidation. The cationic chitosan coating,
      however, improved the oxidative stability to some extent, due to its ability to
      repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant
      activity in both primary and secondary liposomes, which may be attributed to its
      polyphenol content. In conclusion, the best chemical stability of liposomes can
      be achieved using a combination of grape seed extract and chitosan. 

PMID- 24300516
TI  - The Flux of Phenolic Compounds through Silicone Membranes.
AB  - Phenols as a class of molecules have been reported to exhibit higher log maximum
      fluxes through human stratum corneum, SC, from water, log JMHAQ, than other
      classes of molecules. This suggests that their corresponding log maximum fluxes
      through silicone from water, log JMPAQ, may be useful to extend the existing n =
      63 log JMPAQ database to include more log JMPAQ values greater than 0.0. The log
      JMPAQ values for n = 7 phenols predicted to give log JMPAQ values greater than
      0.0 based on their log JMHAQ values have been experimentally determined. These n
      = 7 new log JMPAQ values have been added to the existing n = 63 log JMPAQ
      database to give a new n = 70 database and the n = 7 literature log JMHAQ values
      have been added to the existing n = 48 log JMHAQ database (matched to the n = 63
      log JMPAQ database) to give a new n = 55 database. The addition of the n = 7
      phenols improved the correlations of these flux databases when fitted to the
      Roberts-Sloan equation, RS, as well as the correlation between the matched
      experimental (Exp.) log JMPAQ with the Exp. log JMHAQ. 

PMID- 24300517
TI  - Pectosomes and chitosomes as delivery systems for metronidazole: the one-pot
      preparation method.
AB  - Mucoadhesive liposomes offer a potential for improved residence time of liposomal
      systems targeting contact with mucosal tissues, such as in buccal, oral, colon,
      and vaginal drug delivery. Most of the currently available methods rely on the
      coating of preformed liposomes by various mucoadhesive polymers. The aim of this
      study was to develop novel mucoadhesive system by the one-pot preparation method.
      The pectin- and chitosan-containing liposomes, namely pectosomes and chitosomes,
      were prepared by the modified solvent injection method. In order to optimize this
      novel delivery system, we used pectins and chitosans of both high and low degree
      of esterification/deacetylation (DE/DD), respectively. Sonication was applied to
      reduce the original vesicle size. All vesicles were characterized for their size,
      zeta potential, metronidazole entrapment, and stability. Both pectosomes and
      chitosomes were found to entrap more metronidazole than conventional plain
      liposomes. Preliminary data indicate that the polymer is present on the liposomal
      surface, embedded within inner liposomal bilayers, and entrapped inside the
      aqueous compartment. The next step in the evaluation of this system is the
      testing of its mucoadhesiveness. 

PMID- 24300518
TI  - Bioavailability of polyphenol liposomes: a challenge ahead.
AB  - Dietary polyphenols, including flavonoids, have long been recognized as a source
      of important molecules involved in the prevention of several diseases, including
      cancer. However, because of their poor bioavailability, polyphenols remain
      difficult to be employed clinically. Over the past few years, a renewed interest
      has been devoted to the use of liposomes as carriers aimed at increasing the
      bioavailability and, hence, the therapeutic benefits of polyphenols. In this
      paper, we review the causes of the poor bioavailability of polyphenols and
      concentrate on their liposomal formulations, which offer a means of improving
      their pharmacokinetics and pharmacodynamics. The problems linked to their
      development and their potential therapeutic advantages are reviewed. Future
      directions for liposomal polyphenol development are suggested. 

PMID- 24300520
TI  - Advances in Lipid Nanoparticles for siRNA Delivery.
AB  - Technological advances in both siRNA (small interfering RNA) and whole genome
      sequencing have demonstrated great potential in translating genetic information
      into siRNA-based drugs to halt the synthesis of most disease-causing proteins.
      Despite its powerful promises as a drug, siRNA requires a sophisticated delivery
      vehicle because of its rapid degradation in the circulation, inefficient
      accumulation in target tissues and inability to cross cell membranes to access
      the cytoplasm where it functions. Lipid nanoparticle (LNP) containing ionizable
      amino lipids is the leading delivery technology for siRNA, with five products in
      clinical trials and more in the pipeline. Here, we focus on the technological
      advances behind these potent systems for siRNA-mediated gene silencing. 

PMID- 24300521
TI  - A murine model of subarachnoid hemorrhage.
AB  - In this video publication a standardized mouse model of subarachnoid hemorrhage
      (SAH) is presented. Bleeding is induced by endovascular Circle of Willis
      perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a
      homogenous blood distribution in subarachnoid spaces surrounding the arterial
      circulation and cerebellar fissures is achieved. Animal physiology is maintained
      by intubation, mechanical ventilation, and continuous on-line monitoring of
      various physiological and cardiovascular parameters: body temperature, systemic
      blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral
      perfusion pressure can be tightly monitored resulting in a less variable volume
      of extravasated blood. This allows a better standardization of endovascular
      filament perforation in mice and makes the whole model highly reproducible. Thus
      it is readily available for pharmacological and pathophysiological studies in
      wild type and genetically altered mice. 

PMID- 24300519
TI  - Proteoliposomes as tool for assaying membrane transporter functions and
      interactions with xenobiotics.
AB  - Proteoliposomes represent a suitable and up to date tool for studying membrane
      transporters which physiologically mediate absorption, excretion, trafficking and
      reabsorption of nutrients and metabolites. Using recently developed
      reconstitution strategies, transporters can be inserted in artificial bilayers
      with the same orientation as in the cell membranes and in the absence of other
      interfering molecular systems. These methodologies are very suitable for studying
      kinetic parameters and molecular mechanisms. After the first applications on
      mitochondrial transporters, in the last decade, proteoliposomes obtained with
      optimized methodologies have been used for studying plasma membrane transporters
      and defining their functional and kinetic properties and structure/function
      relationships. A lot of information has been obtained which has clarified and
      completed the knowledge on several transporters among which the OCTN sub-family
      members, transporters for neutral amino acid, B0AT1 and ASCT2, and others.
      Transporters can mediate absorption of substrate-like derivatives or drugs,
      improving their bioavailability or can interact with these compounds or other
      xenobiotics, leading to side/toxic effects. Therefore, proteoliposomes have
      recently been used for studying the interaction of some plasma membrane and
      mitochondrial transporters with toxic compounds, such as mercurials, H2O2 and
      some drugs. Several mechanisms have been defined and in some cases the amino acid
      residues responsible for the interaction have been identified. The data obtained
      indicate proteoliposomes as a novel and potentially important tool in drug
      discovery. 

PMID- 24300522
TI  - Efficient panel designs for longitudinal recurrent event studies recording panel
      counts.
AB  - Many clinical trials are designed to study outcome measures recorded as the
      number of events occurring during specific intervals, called panel data. In such
      data, the intervals are specified by a planned set of follow-up times. As the
      collection of panel data results in a partial loss of information relative to a
      record of the actual event times, it is important to gain a thorough
      understanding of the impact of panel study designs on the efficiency of the
      estimates of treatment effects and covariates. This understanding can then be
      used as a base from which to formulate appropriate designs by layering in other
      concerns, e.g. clinical constraints, or other practical considerations. We
      compare the efficiency of the analysis of panel data with respect to the analysis
      of data recorded precisely as times of recurrences, and articulate conditions for
      efficient panel designs where the focus is on estimation of a treatment effect
      when adjusting for other covariates. We build from the efficiency comparisons to
      optimize the design of panel follow-up times. We model the recurrent intensity
      through the common proportional intensity framework, with the treatment effect
      modeled flexibly as piecewise constant over panels, or groups of panels. We
      provide some important considerations for the design of efficient panel studies,
      and illustrate the methods through analysis of designs of studies of adenomas. 

PMID- 24300523
TI  - Effects of CPAP treatment interruption due to disasters: patients with sleep
      disordered breathing in the Great East Japan Earthquake and tsunami area.
AB  - INTRODUCTION: The 2011 Great East Japan Earthquake caused major disruptions in
      the provision of health care, including that for patients with sleep-disordered
      breathing (SDB) using a nasal continuous positive airway pressure (nCPAP) device.
      This study investigated the ability of SDB patients to continue using the nCPAP
      device in the weeks immediately following the earthquake, whether inability to
      use the nCPAP device led to symptom relapse, and measures that should be taken to
      prevent disruptions in nCPAP therapy during future disasters. Hypothesis If nCPAP
      devices cannot be used during disasters, SDB patients' health will be affected
      negatively. METHODS: Within 14 days of the disaster, 1,047 SDB patients completed
      a questionnaire that collected data regarding ability to use, duration of
      inability to use, and reasons for inability to use the nCPAP device; symptom
      relapse while unable to use the nCPAP device; ability to use the nCPAP device use
      at evacuation sites; and recommendations for improvement of the nCPAP device.
      RESULTS: Of the 1,047 patients, 966 (92.3%) had been unable to use the nCPAP
      device in the days immediately following the earthquake. The most common reason
      for inability to use the nCPAP device was power failure, followed by anxiety
      about sleeping at night due to fear of aftershocks, involvement in disaster
      relief activities, loss of the nasal CPAP device, and fear of being unable to
      wake up in case of an emergency. Among the 966 patients, 242 (25.1%) had
      experienced relapse of symptoms, the most common of which was excessive daytime
      sleepiness (EDS), followed by insomnia, headache, irritability, and chest pain.
      CONCLUSION: Developing strategies for the continuation of nCPAP therapy during
      disasters is important for providing healthy sleeping environments for SDB
      patients in emergency situations.

PMID- 24300524
TI  - Life recovery after disasters: a qualitative study in the Iranian context.
AB  - INTRODUCTION: Planned and organized long-term rehabilitation services should be
      provided to victims of a disaster for social integration, economic self
      sufficiency, and psychological health. There are few studies on recovery and
      rehabilitation issues in disaster situations. This study explores the disaster
      related rehabilitation process. METHOD: This study was based on qualitative
      analysis. Participants included 18 individuals (eight male and ten female) with
      experience providing or receiving disaster health care or services. Participants
      were selected using purposeful sampling. Data were collected through in-depth and
      semi-structured interviews. All interviews were transcribed and content analysis
      was performed based on qualitative content analysis. RESULTS: The study explored
      three main concepts of recovery and rehabilitation after a disaster: 1) needs for
      health recovery; 2) intent to delegate responsibility; and 3) desire for a wide
      scope of social support. The participants of this study indicated that to provide
      comprehensive recovery services, important basic needs should be considered,
      including the need for physical rehabilitation, social rehabilitation, and
      livelihood health; the need for continuity of mental health care; and the need
      for family re-unification services. Providing social activation can help
      reintegrate affected people into the community. CONCLUSION: Effective
      rehabilitation care for disaster victims requires a clear definition of the
      rehabilitation process at different levels of the community. Involving a wide set
      of those most likely to be affected by the process provides a comprehensive,
      continuous, culturally sensitive, and family-centered plan.

PMID- 24300525
TI  - Hospital ships adrift? Part 2: the role of US Navy hospital ship humanitarian
      assistance missions in building partnerships.
AB  - INTRODUCTION: US Navy hospital ships are used as a foreign policy instrument to
      achieve various objectives that include building partnerships. Despite
      substantial resource investment by the Department of Defense (DoD) in these
      missions, their impact is unclear. The purpose of this study was to understand
      how and why hospital ship missions influence partnerships among the different
      participants. METHODS: An embedded case study was used and included the hospital
      ship Mercy's mission to Timor-Leste in 2008 and 2010 with four units of analysis:
      the US government, partner nation, host nation, and nongovernmental
      organizations. Key stakeholders representing each unit were interviewed using
      open-ended questions that explored the experiences of each participant and their
      organization. Findings were analyzed using a priori domains from a proposed
      partnership theoretical framework. A documentary review of key policy, guidance,
      and planning documents was also conducted. RESULTS: Fifteen themes related to how
      and why hospital ship missions influence partnerships emerged from the 37
      interviews and documentary review. The five most prominent included: developing
      relationships, developing new perspectives, sharing resources, understanding
      partner constraints, and developing credibility. Facilitators to joining the
      mission included partner nations seeking a regional presence and senior executive
      relationships. Enablers included historical relationships and host nation
      receptivity. The primary barrier to joining was the military leading the mission.
      Internal constraints included the short mission duration, participant resentment,
      and lack of personnel continuity. External constraints included low host nation
      and United States Agency for International Development (USAID) capacity.
      CONCLUSION: The research finds the idea of building partnerships exists among
      most units of analysis. However, the results show a delay in downstream effects
      of generating action and impact among the participants. Without a common
      partnership definition and policy, guidance, and planning documents reinforcing
      these constructs, achieving the partnership goal will remain challenging. Efforts
      should be made to magnify the facilitators and enablers while developing
      mitigation strategies for the barriers and constraints. This is the first study
      to scientifically assess the partnership impact of hospital ship missions and
      could support the DoD's effort to establish, enable, and sustain meaningful
      partnerships. Application of the findings to improve partnerships in contexts
      beyond hospital ship missions may be warranted and require further analysis. This
      unique opportunity could bridge the rift with humanitarian actors and establish,
      enable, and sustain meaningful partnerships with the DoD.

PMID- 24300526
TI  - Disaster curricula in medical and health care education: adopting an
      interprofessional approach.

PMID- 24300527
TI  - A seed coat bedding assay to genetically explore in vitro how the endosperm
      controls seed germination in Arabidopsis thaliana.
AB  - The Arabidopsis endosperm consists of a single cell layer surrounding the mature
      embryo and playing an essential role to prevent the germination of dormant seeds
      or that of nondormant seeds irradiated by a far red (FR) light pulse. In order to
      further gain insight into the molecular genetic mechanisms underlying the
      germination repressive activity exerted by the endosperm, a "seed coat bedding"
      assay (SCBA) was devised. The SCBA is a dissection procedure physically
      separating seed coats and embryos from seeds, which allows monitoring the growth
      of embryos on an underlying layer of seed coats. Remarkably, the SCBA
      reconstitutes the germination repressive activities of the seed coat in the
      context of seed dormancy and FR-dependent control of seed germination. Since the
      SCBA allows the combinatorial use of dormant, nondormant and genetically modified
      seed coat and embryonic materials, the genetic pathways controlling germination
      and specifically operating in the endosperm and embryo can be dissected. Here we
      detail the procedure to assemble a SCBA. 

PMID- 24300528
TI  - An evaluation of the morphologic features of low-grade mucinous neoplasms of the
      appendix metastatic in the ovary, and comparison with primary ovarian mucinous
      tumors.
AB  - It may be difficult to distinguish ovarian involvement by a low-grade appendiceal
      mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline
      (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within
      a teratoma, particularly when the latter is associated with mucinous
      ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2
      distinctive histologic features, "scalloped" glands and subepthelial stromal
      clefts, whereas IBMTs more often are associated with reactive cellular stroma and
      histiocyte aggregates (mucin granulomas). The frequency of these features was
      investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and
      6 teratoma-associated mucinous tumors (selected on the basis of associated
      pseudomyxoma peritonei). Scalloped glands and subepithelial clefts were
      identified in 17 and 16 LAMNs, respectively, and in 3 and 7 IBMTs, respectively.
      Conversely, reactive stroma and histiocyte aggregates were present in 2 and 0
      LAMNs, respectively, and in 11 and 10 IBMTs, respectively. LAMNs were often
      bilateral (12/18 cases) and they more frequently showed mucin dissection of the
      ovarian stroma and tall mucin-rich (hypermucinous) epithelial cells compared with
      IBMTs. Our findings suggest that scalloped glands, subepithelial clefts, cellular
      stroma, and histiocyte aggregates may be useful additional morphologic parameters
      to help distinguish these tumor types. However, teratoma-associated mucinous
      neoplasms can show identical histologic features to those of LAMNs involving the
      ovary, and therefore accurate diagnosis of such cases requires careful
      macroscopic and microscopic examinations of the ovaries together with complete
      histologic assessment of the appendix. 

PMID- 24300529
TI  - Juvenile granulosa cell tumors: immunoreactivity for CD99 and Fli-1 and EWSR1
      translocation status: a study of 11 cases.
AB  - The accurate diagnosis of a juvenile granulosa cell tumor (JGCT) can be
      challenging, as these neoplasms often exhibit morphologic features that overlap
      other ovarian neoplasms. In addition, the immunohistochemical profile exhibited
      by JGCT is fairly nonspecific and typically includes reactivity for CD99.
      Recently, we noted that JGCTs can show immunohistochemical expression of Fli-1, a
      transcription factor expressed by Ewing sarcoma, a neoplasm that is occasionally
      in the differential diagnosis of JGCT. We evaluated a series of JGCTs to
      determine whether Fli-1 is commonly expressed by these tumors and whether they
      demonstrate chromosomal arrangements in EWSR1. Cases diagnosed as JGCT (n=11)
      were immunohistochemically evaluated for expression of Fli-1 and CD99.
      Fluorescence in situ hybridization was performed on all cases to search for
      chromosomal rearrangements in EWSR1. All 11 of our cases exhibited positive
      immunohistochemical staining for Fli-1 and CD99. None of the cases demonstrated
      rearrangement in EWSR1 by fluorescence in situ hybridization. In cases of JGCT
      that cannot be reliably distinguished from Ewing sarcoma based on morphology and
      immunohistochemistry alone, fluorescence in situ hybridization testing for EWSR1
      rearrangements seems to be a useful diagnostic adjunct for their separation. 

PMID- 24300530
TI  - Interferon-stimulated gene, 15 kDa (ISG15) in ovarian high-grade serous
      carcinoma: prognostic impact and link to NF-kappaB pathway.
AB  - The ubiquitin-like protein interferon-stimulated gene, 15 kDa (ISG15) plays an
      ambiguous role in the progression and response to chemotherapy of solid cancers.
      We aimed to investigate the prognostic impact of ISG15 and its link to the
      nuclear factor kappaB pathway in ovarian high-grade serous carcinoma.
      Immunohistochemistry was performed in a cohort of 128 primary ovarian high-grade
      serous carcinomas treated with standard surgery and adjuvant chemotherapy using
      tissue microarrays. In addition, 28 matched relapsed carcinomas were
      investigated. ISG15 protein expression was significantly increased in relapsed
      carcinomas as compared to primary tumors (P=0.027). In primary carcinoma, ISG15
      was positively associated with total inhibitor of kappaB alpha (IkappaBalpha)
      (P=0.001) as well as nuclear and cytoplasmic phospho-IkappaBalpha (p
      IkappaBalpha) expression (P=0.039 and P=0.002, respectively). Patients with ISG15
      positive carcinomas had a significantly longer overall survival in univariate
      analysis (P=0.002), and in multivariate analysis [hazard ratio=0.35 (95%
      confidence interval, 0.14-0.84, P=0.019)]. ISG15 is a potential prognostic marker
      in high-grade serous carcinoma of the ovary. Its impact on survival might be
      explained by its tight link to the nuclear factor kappaB pathway, and the further
      evaluation of the interplay between ISGylation machinery and nuclear factor
      kappaB, particularly with regard to response to chemotherapy, would be desirable.

PMID- 24300531
TI  - Involuting luteinized thecoma of the ovary.
AB  - Spontaneous tumor involution in ovarian stromal tumors is a poorly understood
      phenomenon. In this report, we describe a rare case of luteinized thecoma that
      showed extensive involutional changes, such that cellular elements diagnostic of
      luteinized thecoma were sparse. The convoluted contour of the tumor resembled
      that observed in a corpus albicans; however, the neoplasm was considerably
      larger, and the contents of the nodule differed from that of a corpus albicans.
      The diagnosis of luteinized thecoma was established by the identification of
      residual aggregates of neoplastic theca cells and a nodule of lutein cells that
      were positive for inhibin and steroidogenic factor-1. Features of involution
      within the tumor included a few theca and lutein cells with pyknotic nuclei and
      abundant cytoplasmic lipid, occasional large adipocytes among the lutein cells,
      extensive hyalinization, dystrophic calcification, a myxohyaline nodule, and
      adipose metaplasia. It is likely that some of the aforementioned changes are the
      result of accompanying ischemia. Cleaved caspase-3 staining patterns were
      negative within residual lutein and theca cells; thus, we were unable to
      establish the occurrence of apoptotic bodies. 

PMID- 24300532
TI  - Fatal case of luteinized thecoma with sclerosing peritonitis in a 40-year-old
      woman.
AB  - We describe the pathologic and clinical presentation of a very rare, fatal case
      of luteinized thecoma with sclerosing peritonitis in a 40-year-old woman, who had
      a history of total abdominal hysterectomy and a left salpingo-oophorectomy in
      2003. The patient presented with abdominal pain, and radiologic examinations
      revealed a 10-cm heterogenous right pelvic mass with partial necrosis. The
      patient eventually underwent an exploratory laparotomy, which revealed an ovarian
      tumor with multiple implants in the peritoneal cavity. The ovarian lesion was
      made up of spindle cells among clusters of luteinized stromal cells that expanded
      to the ovarian cortex. Tumor cells were positive for vimentin, estrogen and
      progesterone receptors, and CCD68 (focally) and negative for CD34, alpha-smooth
      muscle actin, beta-catenin, and desmin by immunohistochemical studies. Luteinized
      cells were positive for alpha-inhibin and calretinin. Tumor cells exhibited low
      Ki-67 proliferation indices. The patient died because of the sclerosing
      peritonitis component of the disease. 

PMID- 24300533
TI  - Epithelioid trophoblastic tumor presenting as an ovarian mass in a postmenopausal
      woman.
AB  - Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic
      type intermediate trophoblastic cells. Most cases of ETT are intrauterine and
      present during reproductive age. We report a case of ovarian ETT developing 47 yr
      after the patient's last pregnancy. A 75-yr-old woman transferred to our hospital
      because of multiple pulmonary masses which was diagnosed as sqaumous cell
      carcinoma in another hospital. PET-CT revealed a huge solid mass in the pelvic
      cavity, suspicious for ovarian malignancy. Serum beta-hCG was 57,971 mIU/mL.
      Hysterectomy and bilateral salpingo-oophorectomy were performed. Gross
      examination showed an enlarged right ovary, measuring 17*14*7 cm. The cut surface
      was yellow-tan and solid with extensive areas of necrosis. The uterus was
      unremarkable. The histologic finding was the same as the previous lung biopsy.
      The tumor consisted of monomorphic cells with abundant eosinophilic cytoplasm,
      forming solid sheets and nests. There was geographic tumor cell necrosis with
      hyaline materials. Immunohistochemically, cytokeratin 7 and p63 showed diffuse
      reactivity in the tumor cells. There was focal staining for beta-hCG. Ki-67
      proliferative index was about 80%. This case indicates that ETT can rarely occur
      in postmenopausal women and to the best of our knowledge, our patient is the
      oldest reported case of ETT to date. 

PMID- 24300534
TI  - Unusual calcifying fibrous tumor in the fallopian tube: review and discussion of
      the differential diagnosis.
AB  - Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown
      etiology and extremely rare in female reproductive system. We present a case of
      unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female
      patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48
      year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined
      nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of
      ampulla of right fallopian tube. The lesion of fallopian tube was resected
      totally. Histologically, this lesion was unencapsulated and composed of
      hyalinized collagenous fibrous tissue with psammomatous calcification and focal
      lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were
      scattered in the dense hyalinized background with bland nuclei. By
      immunohistochemistry, vimentin was diffusely positive in most cells, and a focal
      reactivity for CD34 was also observed in spindle cells. However, they were
      negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and
      ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT
      of fallopian tube was made. To our knowledge, this is the first report of CFT
      occurring in female reproductive tract. Awareness of CFT and its distinctive
      features is important to avoid a diagnostic pitfall caused by histologic
      similarities to other spindle cell or calcifying lesions in unusual locations.
      Although marginal excision is usually adequate for most of CFT, long-term follow
      up is suggested as delayed recurrence might occur infrequently. 

PMID- 24300535
TI  - The multidrug-resistance transporter ABCB5 is expressed in human placenta.
AB  - ATP-binding cassette (ABC) transporters in placenta protectively transport drugs
      and xenobiotics. ABCB5 [subfamily B (MDR/TAP)] is a novel ABC multidrug
      resistance transporter that also mediates cell fusion, stem cell function, and
      vasculogenic plasticity. Immunohistochemistry and double-labeling
      immunofluorescence staining for ABCB5 and ABCB5/CD200, respectively, was
      performed on formalin-fixed, paraffin-embedded placental tissue from 5 first
      trimester, 5 second trimester, and 5 term pregnancies as well as 5 partial moles,
      and 5 complete moles. In addition, tumor cells from 5 choriocarcinoma and 5
      placental site trophoblastic tumor cases were examined. ABCB5 staining was
      observed in villous trophoblasts in 100% (5/5) of first trimester placentas (with
      progressive decrease in term placentas); 100% of partial moles (5/5); and 100% of
      complete moles (5/5). Notably, reactivity was discretely restricted to the inner
      trophoblast layer, with no staining of overlying syncytiotrophoblast. Antibody
      specificity and localization was confirmed further by in situ hybridization.
      ABCB5 expression was retained in 20% of choriocarcinomas (1/5) and 40% of
      placental site trophoblastic tumors (2/5). Prior studies have localized
      expression of multidrug-resistance-1, also known as ABCB1, within the
      syncytiotrophoblast of early placentas, where it serves a protective function as
      an efflux transporter. Our results show that ABCB5 is preferentially expressed in
      the cytotrophoblast layer of placental villi. The expression of this novel
      biomarker at the maternal-fetal interface raises questions on its role in
      placental structure and function as well as on its potential contribution to the
      protective efflux provided by other P-glycoprotein transporters. 

PMID- 24300536
TI  - Nodular histiocytic aggregates in the endometrium: a report of 7 cases.
AB  - Nodular aggregates of nonfoamy histiocytes in the endometrium are uncommon. We
      describe herein the clinical and pathologic characteristics of 7 additional cases
      in endometrial biopsies or curettages. The patients ranged in age from 48 to 72
      years, and the most common presenting symptom was abnormal uterine bleeding. Five
      of seven patients had undergone prior endometrial sampling (including 1 who had
      undergone 3 endometrial biopsies over the preceding 5 yr for follow-up of
      abnormal uterine bleeding). In 2 cases, an endometrial polyp was present in the
      same sample, and an additional 2 were found to have endometrial polyps on
      subsequent biopsies that were performed within 4 months of original samplings.
      The lesions, which ranged in size from 1 to 8 mm, were composed of monomorphic
      cells with abundant pink eosinophilic cytoplasm with a vaguely nodular
      arrangement. Two cases showed focally high mitotic activity with up to 4 mitoses
      per high-power field. Patient outcomes were unremarkable, which affirms the
      benign nature of the proliferation. Several features of this lesion, including
      mitotic activity, focal necrosis, and tight aggregation of cells, may raise the
      possibility of a neoplastic proliferation. This differential diagnosis can be
      readily resolved by awareness of the lesion and immunohistochemical analyses.
      Possible pathogenetic considerations are discussed, but these nodules represent,
      in our opinion, reaction to necrotic tissue in the endometrial cavity, possibly
      related to prior procedure. 

PMID- 24300537
TI  - Genotyping diagnosis of nongestational choriocarcinoma involving fallopian tube
      and broad ligament: a case study.
AB  - A 22 year-old G1P1 woman presented to the emergency room with clinical impression
      of "ruptured right adnexal mass" and underwent a right salpingo-oophorectomy to
      rule out ectopic pregnancy. Instead, gross and microscopic examination revealed a
      pure choriocarcinoma involving the right fallopian tube and broad ligament. On
      the basis of the patient's age, recent history of delivery, last menstrual period
      for 10 weeks, large tumor mass, and possible pelvic lymph node metastasis, the
      patient promptly started to receive 8 cycles of multiagent chemotherapy regimen
      with a working diagnosis of high-risk gestational choriocarcinoma. Subsequent DNA
      genotyping analysis showed that the tumor cells had an identical genetic profile
      to that of the normal tissue of the patient, therefore establishing a final
      diagnosis of nongestational choriocarcinoma. Six months after the initial
      presentation, a second surgery was performed to remove a persistent right para
      adnexal mass, which showed only necrotic tissue upon microscopic examination. The
      patient received 1 additional cycle of multiagent chemotherapy. She was alive
      without evidence of recurrence 26 months after the initial diagnosis. 

PMID- 24300538
TI  - Lymphoepithelioma-like carcinoma of the endometrium: immunophenotypic
      characterization of a rare tumor with microsatellite instability testing.
AB  - This report describes the clinicopathologic features of a primary
      lymphoepithelioma-like carcinoma of the endometrium, representing only the fourth
      reported case of this tumor at this location. In addition to its classic
      morphologic features, focal clear cells were also identified within the tumor,
      thereby expanding the morphologic spectrum of the neoplasm at this location. A
      comprehensive immunohistochemical characterization of the tumor was performed, as
      was microsatellite instability testing. The tumor was diagnosed in a 79-year-old
      woman and was surgically/pathologically staged as IB by the International
      Federation of Gynecology and Obstetrics (FIGO) criteria. The tumor displayed
      typical morphologic features (tumor cells with a syncytial appearance in an
      inflammatory background) with the exception of the aforementioned polygonal cells
      with well-defined cell membranes and cytoplasmic clarity in <1% of the tumor. The
      epithelial component showed strong and diffuse immunoreactivity for CAM 5.2, p53,
      p16, E-cadherin, cytokeratin (CK) 7, vimentin, CKAE1/3, and epithelial membrane
      antigen. The MIB-1 proliferative index in these regions was about 70%.
      Approximately 10% to 30% of lesional cells showed strong immunoreactivity for
      CK903, S100, MOC31, CD138, but the pattern of positivity was patchy and
      discontinuous. The epithelial cells were entirely negative for CK5/6, smooth
      muscle actin, p504S, CK20, synaptophysin, chromogranin, CD56, CD99, WT-1, thyroid
      transcription factor-1, p63, CD117 (c-kit), CD34, calretinin, desmin, estrogen
      receptor, progesterone receptor, FLI-1, ALK-1, D2-40, cytomegalovirus antigen,
      Epstein-Barr virus-encoded RNA-1, Epstein-Barr virus, monoclonal carcinoembryonic
      antigen, and HER2/neu. The foci with clear cells were not immunophenotypically
      distinct from the non-clear cell areas and had an approximately similar
      proliferative index. The inflammatory component was mixed (lymphocytes,
      histiocytes, plasma cells, neutrophils) but was composed predominantly of
      CD45/CD3/CD8 T lymphocytes, with a CD3 to CD20 ratio of approximately 10:1 and
      CD8 to CD4 T-cell ratio of approximately 3:1. Numerous (>100 positive cells per
      10 high-power fields) S100-positive tumor-infiltrating Langerhans cells were
      present. The tumor DNA did not exhibit microsatellite instability at any of the
      loci analyzed. In summary, the limited data available suggest that
      lymphoepithelioma-like carcinoma is a distinct histotype of endometrial carcinoma
      that is typically seen in postmenopausal women, seems to be unrelated to the
      Epstein-Barr virus, and has an uncertain prognosis. Differential diagnostic and
      pathogenetic considerations are discussed within the context of the lesional
      morphologic and immunophenotypic profile as described herein and in previously
      reported cases. 

PMID- 24300539
TI  - Evaluation of p16(INK4a) overexpression in a large series of cervical carcinomas:
      concordance with SPF10-LiPA25 PCR.
AB  - The aims of this study were to assess the overexpression of p16 in formalin-fixed
      paraffin-embedded cervical carcinoma tissue blocks and to determine its
      concordance with the human papillomavirus (HPV) status using the SPF10-LiPA25
      polymerase chain reaction System and its correlation with the histologic type of
      invasive cervical cancer (ICC) and individual HPV genotypes. A total of 205
      retrospectively collected ICC cases were analyzed by p16 immunohistochemistry.
      HPV detection was performed by polymerase chain reaction using SPF10 broad
      spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and
      genotyping by reverse hybridization line probe assay (LiPA25). Of 205, 188
      analyzed (91.7%) ICC cases showed p16 overexpression, whereas 181 (83.3%) cases
      were HPV positive using HPV LiPA testing. One hundred and seventy four (84.9%)
      cases were both p16 and HPV LiPA positive, indicating a positive concordance of
      89.9% between both techniques (kappa index agreement of 0.43; P<0.001), and no
      statistically significant difference (McNemar test, P>0.05). Squamous cell
      carcinomas were strongly positive compared with the adenocarcinomas (93.6% vs.
      75% of the cases, respectively). When performed on formalin-fixed paraffin
      embedded cervical tissue specimens, the higher positivity rate of p16
      immunohistochemistry as compared with HPV DNA testing may allow identifying HPV
      related ICC cases in which HPV testing was negative. 

PMID- 24300540
TI  - Positive margin status in uterine cervix cone specimens is associated with
      persistent/recurrent high-grade dysplasia.
AB  - The frequency of positive cone margins and its significance in cervical
      intraepithelial neoplasia are under controversy. The purpose of the current study
      was to identify factors associated with positive cone margin status and to
      evaluate its clinical significance in high-grade cervical intraepithelial
      neoplasia. Medical records of women who underwent loop electrosurgical excision
      procedure at the Soroka Medical Center (January 2001-July 2011) were reviewed
      retrospectively. Patient age, extent of dysplasia, endocervical glands
      involvement, positive margin status, type of margin involved, degree of margin
      involvement, and postcone endocervical curettage results were evaluated as
      possible factors associated with persistent/recurrent disease. A total of 376
      women were included in the study. Cone margin involvement was observed in 33%
      (endocervical-22%, ectocervical-8%, both margins-3%). Factors significantly
      associated with cone margin involvement were older age (older than 35 y),
      widespread dysplasia in the cone specimen (>=4 sections) (P<0.001 for each), and
      endocervical glands involvement (P=0.003). Fifty patients (13%) had
      persistent/recurrent disease. Involvement of the cone margins (focal: hazard
      ratio=17, P<0.001; extensive: hazard ratio=28, P<0.001) and older age (hazard
      ratio=1.18 for every 5 additional years, P=0.03) were associated with
      persistent/recurrent disease. We conclude that women older than 35 yr with
      widespread high-grade dysplasia in the cone specimen and involvement of
      endocervical glands are more likely to have positive cone margins. Positive cone
      margins, particularly when extensively involved, and increased patient age are
      associated with persistent/recurrent disease. These factors should be considered
      while planning for further management. 

PMID- 24300541
TI  - The spectrum of grossly visible pigmented lesions in the uterine cervix: a
      prospective study.
AB  - Pigmented lesions of the uterine cervix (UC) have not been systematically studied
      in the literature. Over an 18-mo period, we prospectively investigated the
      histologic spectrum of all macroscopically visible pigmented lesions of the UC.
      The incidence of pigmented UC was 1.6% (33/2118). Histologic examination revealed
      32 cases (97%) with a histologic correlate, of which 26 lesions were of
      melanocytic nature including 25 blue nevi (BNs) (81%) and 1 melanotic macule
      (3%). The nonmelanocytic lesions included 1 case of focal granulomatous
      vasculitis (3%), 2 biopsy site-associated reactive changes with hemosiderin-laden
      macrophages (6.4%), 1 case of hemorrhagic Nabothian cyst (3%), 1 hemangioma (3%),
      and 1 case of multinucleated giant cell reaction to dark black carbon-like
      material (3%). Women with UC BN (1.2% incidence) were mostly whites (13/25, 52%)
      with a mean age of 47.4 yr (range, 31-64 yr). The number and size of BN per UC,
      all located in the endocervix, varied between 1 to 3 and 0.1 to 2 cm (mean, 0.68
      cm). UC BN exhibited 3 distinct morphologic patterns: (1) stromal melanocytic
      focus composed of fine spindle cells (9/25, 36%); (2) mixed pattern with fine
      spindle, plump spindle, and epithelioid cells (15/25, 60%); and (3) nevoid stage
      with epithelioid cells (1/25, 4%). In contrast, cervical melanotic macule was
      located in the squamous epithelium of the ectocervix and characterized by
      hyperpigmentation of the basal keratinocytes admixed with scattered slightly
      enlarged melanocytes. In conclusion, pigmented lesions of the UC are not as
      uncommon as reported and mostly benign in nature. Several cases may require
      deeper levels for their detection and to exclude the rare phenomenon of UC
      melanoma. 

PMID- 24300542
TI  - Cystic fibrosis involving the cervix, mimicking a well-differentiated
      adenocarcinoma: a case report.
AB  - We describe clinicopathologic and immunohistochemical features of an unusual case
      of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical
      adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy
      postcoital vaginal bleeding 4 months after starting oral contraceptives and was
      found to have a cervical mass. She underwent a loop electrosurgical excision of
      the mass, and microscopic examination revealed a florid endocervical
      proliferation, extending to the margins. This lesion was initially interpreted as
      an invasive, well-differentiated endocervical adenocarcinoma. However, on
      subsequent review, the lesion was found to have a low rate of proliferation, no
      evidence of an infiltrative growth pattern, and abundant acute inflammation.
      Given these findings and the absence of any residual endocervical lesion on a
      subsequent cold knife conization, we determined that this was a benign, likely
      reactive, lesion. This case, together with previous studies, suggests that women
      with cystic fibrosis can develop proliferative endocervical lesions and that oral
      contraceptives may contribute to their development. 

PMID- 24300543
TI  - Model for regulation of VAMP721/722-mediated secretion: growth vs. stress
      responses.
AB  - The PEN1-SNAP33-VAMP721/722 exocytic pathway is a conserved immunity-associated
      secretory pathway between monocotyledonous barley and dicotyledonous Arabidopsis
      plants. In Arabidopsis, this secretory pathway plays an additional role in plant
      growth and development. However, how this pathway can be manipulated to engage in
      both growth/development and immunity remains to be answered. To understand its
      regulation, we recently analyzed the expression of VAMP721/722 genes whose
      products drive secretory vesicles to the target plasma membrane. By investigating
      their transcript and protein levels, we found that plants distinctly control the
      activity of this secretory pathway during biotic or abiotic stress responses.
      Since stress responses are in general accompanied by growth inhibition in plants
      and since plants in nature are simultaneously threatened by a number of
      environmental stresses, understanding of this growth/immunity-related secretory
      pathway would help to generate more efficiently growth/immunity-balancing plants.

PMID- 24300545
TI  - Epidemiologic contributions to recent cancer trends among HIV-infected people in
      the United States.
AB  - OBJECTIVE: HIV-infected people have elevated risk for some cancers. Changing
      incidence of these cancers over time may reflect changes in three factors: HIV
      population demographic structure (e.g. age distribution), general population
      (background) cancer rates, and HIV-associated relative risks. We assessed the
      contributions of these factors to time trends for 10 cancers during 1996-2010.
      DESIGN: Population-based registry linkage study. METHODS: We applied Poisson
      models to data from the U.S. HIV/AIDS Cancer Match Study to estimate annual
      percentage changes (APCs) in incidence rates of AIDS-defining cancers [ADCs:
      Kaposi sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer] and seven non
      AIDS-defining cancers (NADCs). We evaluated HIV-infected cancer trends with and
      without adjustment for demographics, trends in background rates, and trends in
      standardized incidence ratios (SIRs, to capture relative risk). RESULTS: Cancer
      rates among HIV-infected people rose over time for anal (APC 3.8%), liver (8.5%),
      and prostate (9.8%) cancers, but declined for Kaposi sarcoma (1996-2000: -29.3%;
      2000-2010: -7.8%), NHL (1996-2003: -15.7%; 2003-2010: -5.5%), cervical cancer (
      11.1%), Hodgkin lymphoma (-4.0%), and lung cancer (-2.8%). Breast and colorectal
      cancer incidence did not change over time. Based on comparison to adjusted
      models, changing demographics contributed to trends for Kaposi sarcoma and
      breast, colorectal, liver, lung, and prostate cancers (all P < 0.01). Trends in
      background rates were notable for liver (APC 5.6%) and lung (-3.2%) cancers. SIRs
      declined for ADCs, Hodgkin lymphoma (APC -3.2%), and lung cancer (-4.4%).
      CONCLUSION: Demographic shifts influenced several cancer trends among HIV
      infected individuals. Falling relative risks largely explained ADC declines,
      while background incidence contributed to some NADC trends.

PMID- 24300546
TI  - HIV infection and the fronto-striatal system: a systematic review and meta
      analysis of fMRI studies.
AB  - Functional MRI studies investigating the impact of HIV on the brain have
      implicated the involvement of fronto-striatal circuitry. However, to date there
      is no review and meta-analysis of this work. We systematically reviewed the
      literature and performed a meta-analysis of functional magnetic resonance imaging
      (fMRI) studies in HIV-infected individuals using a well validated tool recently
      developed for use in fMRI, 'GingerALE'. Twenty-one studies (468 HIV+, 270 HIV-
      controls) were qualitatively reviewed, of which six (105 HIV+, 102 controls)
      utilized fMRI paradigms engaging the fronto-striatal-parietal network, making a
      quantitative analysis possible. Our meta-analysis revealed consistent functional
      differences in the left inferior frontal gyrus and caudate nucleus between
      infected participants and controls across these studies. This fronto-striatal
      dysfunction was qualitatively related to cognitive impairment, disease
      progression and treatment effects. Although further work needs to be done to
      further delineate the potentially confounding influence of substance abuse and
      HIV-related comorbidities, as well as HIV's effect on functional haemodynamic
      vascular coupling, these findings indicate that further investigation of the
      fronto-striatal sub-networks in HIV-infected patients is warranted. 

PMID- 24300547
TI  - Existence and global exponential stability of periodic solution for high-order
      discrete-time BAM neural networks.
AB  - This paper concerns the existence and exponential stability of periodic solution
      for the high-order discrete-time bidirectional associative memory (BAM) neural
      networks with time-varying delays. First, we present the criteria for the
      existence of periodic solution based on the continuation theorem of coincidence
      degree theory and the Young's inequality, and then we give the criteria for the
      global exponential stability of periodic solution by using a non-Lyapunov method.
      After that, we give a numerical example that demonstrates the effectiveness of
      the theoretical results. The criteria presented in this paper are easy to verify.
      In addition, the proposed analysis method is easy to extend to other high-order
      neural networks. 

PMID- 24300548
TI  - Semi-supervised learning of class balance under class-prior change by
      distribution matching.
AB  - In real-world classification problems, the class balance in the training dataset
      does not necessarily reflect that of the test dataset, which can cause
      significant estimation bias. If the class ratio of the test dataset is known,
      instance re-weighting or resampling allows systematical bias correction. However,
      learning the class ratio of the test dataset is challenging when no labeled data
      is available from the test domain. In this paper, we propose to estimate the
      class ratio in the test dataset by matching probability distributions of training
      and test input data. We demonstrate the utility of the proposed approach through
      experiments. 

PMID- 24300549
TI  - Cellular computational networks--a scalable architecture for learning the
      dynamics of large networked systems.
AB  - Neural networks for implementing large networked systems such as smart electric
      power grids consist of multiple inputs and outputs. Many outputs lead to a
      greater number of parameters to be adapted. Each additional variable increases
      the dimensionality of the problem and hence learning becomes a challenge.
      Cellular computational networks (CCNs) are a class of sparsely connected dynamic
      recurrent networks (DRNs). By proper selection of a set of input elements for
      each output variable in a given application, a DRN can be modified into a CCN
      which significantly reduces the complexity of the neural network and allows use
      of simple training methods for independent learning in each cell thus making it
      scalable. This article demonstrates this concept of developing a CCN using
      dimensionality reduction in a DRN for scalability and better performance. The
      concept has been analytically explained and empirically verified through
      application. 

PMID- 24300550
TI  - Pointwise probability reinforcements for robust statistical inference.
AB  - Statistical inference using machine learning techniques may be difficult with
      small datasets because of abnormally frequent data (AFDs). AFDs are observations
      that are much more frequent in the training sample that they should be, with
      respect to their theoretical probability, and include e.g. outliers. Estimates of
      parameters tend to be biased towards models which support such data. This paper
      proposes to introduce pointwise probability reinforcements (PPRs): the
      probability of each observation is reinforced by a PPR and a regularisation
      allows controlling the amount of reinforcement which compensates for AFDs. The
      proposed solution is very generic, since it can be used to robustify any
      statistical inference method which can be formulated as a likelihood
      maximisation. Experiments show that PPRs can be easily used to tackle regression,
      classification and projection: models are freed from the influence of outliers.
      Moreover, outliers can be filtered manually since an abnormality degree is
      obtained for each observation. 

PMID- 24300544
TI  - Interleukin-6 and D-dimer levels at seroconversion as predictors of HIV-1 disease
      progression.
AB  - OBJECTIVE: Inflammation and coagulation biomarkers interleukin (IL)-6 and D-dimer
      are predictive of all-cause mortality in chronic HIV-1 infection; however, their
      predictive value in individuals with recent infection has not been described.
      METHODS: SPARTAC was a randomized controlled trial comparing three strategies of
      intervention in primary HIV-1 infection [no therapy, 12-week or 48-week
      antiretroviral therapy (ART)]. Plasma IL-6 and D-dimer were measured in 200
      participants from sites in Australia, Brazil, UK and Italy. We evaluated age,
      sex/HIV risk group, time since HIV-1 seroconversion, baseline HIV-RNA, CD4 cell
      count and BMI as possible predictors of IL-6 and D-dimer levels at seroconversion
      using multivariable linear regression. For participants remaining ART-naive, we
      evaluated whether baseline IL-6 and D-dimer levels independently predicted time
      to reaching CD4 cell count less than 350 cells/MUl or initiating ART using
      multivariable Cox proportional hazards models. RESULTS: Median (interquartile
      range, IQR) baseline IL-6 and D-dimer levels were 1.45 (0.88-2.41) pg/ml and 0.34
      (0.20-0.50) MUg/l, respectively. Higher levels were associated with older age
      (P=0.008 and 0.004, respectively). Higher D-dimer levels were associated with
      higher HIV-RNA (P<0.001). For the 73 participants not initiating ART (median
      follow-up 225 weeks), of whom 48 reached the primary endpoint, higher baseline IL
      6, but not D-dimer, was independently associated with a shorter time to primary
      endpoint [hazard ratio=1.38 per additional pg/ml, 95% confidence interval (CI)
      1.09-1.75; P=0.007]. Other baseline predictors were older age (P=0.030), higher
      RNA (P=0.033) and lower CD4 cell count (P<0.001). CONCLUSION: IL-6 levels at time
      of HIV-1 seroconversion independently predict HIV-1 disease progression in
      patients with primary HIV-1 infection.

PMID- 24300551
TI  - A linear recurrent kernel online learning algorithm with sparse updates.
AB  - In this paper, we propose a recurrent kernel algorithm with selectively sparse
      updates for online learning. The algorithm introduces a linear recurrent term in
      the estimation of the current output. This makes the past information reusable
      for updating of the algorithm in the form of a recurrent gradient term. To ensure
      that the reuse of this recurrent gradient indeed accelerates the convergence
      speed, a novel hybrid recurrent training is proposed to switch on or off learning
      the recurrent information according to the magnitude of the current training
      error. Furthermore, the algorithm includes a data-dependent adaptive learning
      rate which can provide guaranteed system weight convergence at each training
      iteration. The learning rate is set as zero when the training violates the
      derived convergence conditions, which makes the algorithm updating process
      sparse. Theoretical analyses of the weight convergence are presented and
      experimental results show the good performance of the proposed algorithm in terms
      of convergence speed and estimation accuracy. 

PMID- 24300552
TI  - Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor
      and nonprogressor individuals alter Vpr-associated functions.
AB  - Following infection with Human immunodeficiency virus 1 (HIV-1) there is a
      remarkable variation in virus replication and disease progression. Both host and
      viral factors have been implicated in the observed differences in disease status.
      Here, we focus on understanding the contribution of HIV-1 viral protein R (Vpr)
      by evaluating the disease-associated Vpr polymorphism and its biological
      functions from HIV-1 positive rapid progressor (RP) and long-term nonprogressor
      (LTNP) subjects. Results presented here show distinct variation in phenotypes of
      Vpr alleles from LTNP and RP subjects. Most notably, the polymorphism of Vpr at
      R36W and L68M associated with RP shows higher levels of oligomerization, and
      increased virus replication, whereas R77Q exhibits poor replication kinetics.
      Interestingly, we did not observe correlation with cell cycle arrest function.
      Together these results indicate that polymorphisms in Vpr in part may contribute
      to altered virus replication kinetics leading to the observed differences in
      disease progression in LTNP and RP groups. 

PMID- 24300553
TI  - Intrahaemocoelic infection of Trichoplusia ni with the baculovirus Autographa
      californica M nucleopolyhedrovirus does not induce tracheal cell basal lamina
      remodelling.
AB  - Infection of the lepidopteran insect Trichoplusia ni with the baculovirus
      Autographa californica M nucleopolyhedrovirus (AcMNPV) by the oral route
      stimulates activation of host matrix metalloproteases (MMP) and effector
      caspases, a process dependent on expression of the viral fibroblast growth factor
      (vFGF). This pathway leads to tracheal cell basal lamina remodelling, enabling
      virus escape from the primary site of infection, the midgut epithelium, and
      establishment of efficient systemic infection. In this study, we asked whether
      the MMP-caspase pathway was also activated following infection by
      intrahaemocoelic injection. We found that intrahaemocoelic infection did not lead
      to any observable tracheal cell or midgut epithelium basal lamina remodelling.
      MMP and caspase activities were not significantly stimulated. We conclude that
      the main role of the AcMNPV vFGF is in facilitating virus midgut escape. 

PMID- 24300554
TI  - Multi-resolution correlative focused ion beam scanning electron microscopy:
      applications to cell biology.
AB  - Efficient correlative imaging of small targets within large fields is a central
      problem in cell biology. Here, we demonstrate a series of technical advances in
      focused ion beam scanning electron microscopy (FIB-SEM) to address this issue. We
      report increases in the speed, robustness and automation of the process, and
      achieve consistent z slice thickness of ~3 nm. We introduce "keyframe imaging" as
      a new approach to simultaneously image large fields of view and obtain high
      resolution 3D images of targeted sub-volumes. We demonstrate application of these
      advances to image post-fusion cytoplasmic intermediates of the HIV core. Using
      fluorescently labeled cell membranes, proteins and HIV cores, we first produce a
      "target map" of an HIV infected cell by fluorescence microscopy. We then generate
      a correlated 3D EM volume of the entire cell as well as high-resolution 3D images
      of individual HIV cores, achieving correlative imaging across a volume scale of
      10(9) in a single automated experimental run.

PMID- 24300555
TI  - Expansive generation of functional airway epithelium from human embryonic stem
      cells.
AB  - Production of human embryonic stem cell (hESC)-derived lung progenitors has broad
      applicability for drug screening and cell therapy; however, this is complicated
      by limitations in demarcating phenotypic changes with functional validation of
      airway cell types. In this paper, we reveal the potential of hESCs to produce
      multipotent lung progenitors using a combined growth factor and physical culture
      approach, guided by the use of novel markers LIFRalpha and NRP1. Lung
      specification of hESCs was achieved by priming differentiation via matrix
      specific support, followed by air-liquid interface to allow generation of lung
      progenitors capable of in vitro maturation into airway epithelial cell types,
      resulting in functional characteristics such as secretion of pulmonary
      surfactant, ciliation, polarization, and acquisition of innate immune activity.
      This approach provided a robust expansion of lung progenitors, allowing in vivo
      assessment, which demonstrated that only fully differentiated hESC-derived airway
      cells were retained in the distal airway, where they aided in physiological
      recovery in immunocompromised mice receiving airway injury. Our study provides a
      basis for translational applications of hESCs for lung diseases. 

PMID- 24300557
TI  - [Jeavons syndrome: importance of differential diagnosis in epilepsy].

PMID- 24300556
TI  - Concise review: cell-based strategies in bone tissue engineering and regenerative
      medicine.
AB  - Cellular strategies play an important role in bone tissue engineering and
      regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g.,
      cell types, cell isolation and expansion, cell seeding methods, and preculture
      conditions before in vivo implantation) may influence experimental outcome.
      Meanwhile, outcomes from initial clinical trials are far behind those of animal
      studies, which is suggested to be related to insufficient nutrient and oxygen
      supply inside the BTE/RM constructs as some complex clinical implementations
      require bone regeneration in too large a quantity. Coculture strategies, in which
      angiogenic cells are introduced into osteogenic cell cultures, might provide a
      solution for improving vascularization and hence increasing bone formation for
      cell-based constructs. So far, preclinical studies have demonstrated that cell
      based tissue-engineered constructs generally induce more bone formation compared
      with acellular constructs. Further, cocultures have been shown to enhance
      vascularization and bone formation compared with monocultures. However,
      translational efficacy from animal studies to clinical use requires improvement,
      and the role implanted cells play in clinical bone regeneration needs to be
      further elucidated. In view of this, the present review provides an overview of
      the critical procedures during in vitro and in vivo phases for cell-based
      strategies (both monoculture and coculture) in BTE/RM to achieve more
      standardized culture conditions for future studies, and hence enhance bone
      formation. 

PMID- 24300558
TI  - Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the
      treatment of endometrial cancer with peritoneal carcinomatosis.
AB  - OBJECTIVE: To investigate the benefit of cytoreductive surgery combined with
      hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of
      endometrial peritoneal carcinomatosis. STUDY DESIGN: Preoperative, intraoperative
      and postoperative data were collected prospectively for 13 patients treated in
      our University hospital. RESULTS: Of the thirteen patients treated, one patient
      was lost to follow up. Three patients died within the first twelve months of
      treatment, and two patients died at respectively 12.4 and 19.4 months after the
      HIPEC procedure. Seven patients are alive, four of them without recurrence,
      between 1.5 and 124.8 months after surgery. The Peritoneal Cancer Index (PCI) and
      the Completeness of Cytoreduction-Score (CC-S) are prognostic factors for
      survival after HIPEC treatment for peritoneal carcinomatosis of endometrial
      origin. CONCLUSIONS: The significant survival time in selected patients should
      lead to a study of the management of peritoneal carcinomatosis of endometrial
      origin in a larger number of cases, and justifies a clinical trial on a larger
      scale.

PMID- 24300559
TI  - Pain perception during outpatient cystoscopy: a prospective controlled study.
AB  - OBJECTIVE: Rigid cystoscopy is a common diagnostic tool in the assessment of
      lower urinary tract symptoms, but it is an invasive procedure which can cause
      distress. Data exist about pain perception during cystoscopy in male patients but
      only a few data are available in women. The purpose of this study was to
      investigate pain perception in urogynecologic patients during cystoscopy and
      compare it with pain perception during urodynamics. We also investigated the
      difference between anticipated and actual pain perception. STUDY DESIGN: A
      cooperative, non-randomized cohort study was performed including 109 women with
      pelvic floor dysfunction scheduled for outpatient cystoscopy or urodynamic
      testing. Patients completed a questionnaire and a visual analog scale (VAS, 0-10
      cm) before and after examination. Patients were called one day after examination
      and asked about pain and their general state of health. According to power
      calculation, a sample size of 52 patients per group was needed to detect a 2 cm
      difference in pain scores on the VAS - judged as a clinically significant - with
      95% power and a two-sided significance level of 0.05. RESULTS: In 57 patients
      undergoing cystoscopy versus 52 patients undergoing urodynamics, the main pain
      scores on VAS were 1.9 cm for cystoscopy and 1.2 cm for urodynamics (p=0.03).
      Patients in both groups anticipated more pain than they actually experienced:
      2.7+/-2.4 before versus 1.9+/-1.8 after cystoscopy (p<0.01) and 2.1+/-2.4 before
      versus 1.2+/-1.6 after urodynamics (p<0.01). CONCLUSION: Patients experience
      cystoscopy as more painful than urodynamics. Patients anticipate both cystoscopy
      and urodynamics to be more painful than they actually are.

PMID- 24300560
TI  - Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide
      cocrystal solubility and dissolution behaviour.
AB  - The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on
      carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution
      behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal
      was determined by measuring the eutectic concentrations of the drug and the
      coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC
      cocrystal was monitored by the UV imaging dissolution system during dissolution.
      Experimental results indicated that SLS and Tween 80 had little influence upon
      the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on
      the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased
      the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR. 

PMID- 24300561
TI  - Liposome formulation of fullerene-based molecular diagnostic and therapeutic
      agents.
AB  - Fullerene medicine is a new but rapidly growing research subject. Fullerene has a
      number of desired structural, physical and chemical properties to be adapted for
      biological use including antioxidants, anti-aging, anti-inflammation,
      photodynamic therapy, drug delivery, and magnetic resonance imaging contrast
      agents. Chemical functionalization of fullerenes has led to several interesting
      compounds with very promising preclinical efficacy, pharmacokinetic and safety
      data. However, there is no clinical evaluation or human use except in fullerene
      based cosmetic products for human skincare. This article summarizes recent
      advances in liposome formulation of fullerenes for the use in therapeutics and
      molecular imaging. 

PMID- 24300563
TI  - Design of olanzapine/lutrol solid dispersions of improved stability and
      performances.
AB  - Eleven solid dispersions containing olanzapine, with carriers of different
      composition (Lutrol(r) F68, Lutrol(r) F127, Gelucire(r) 44/14), were prepared and
      examined by thermal (differential scanning calorimetry (DSC); thermomicroscopy
      (HSM)) and X-ray diffraction (XRD) analysis, both as fresh or aged (one year)
      samples. Drug and carriers were preliminarily selected in order to avoid problems
      related to the aging of the formulation, according to the solubility parameters
      of carriers and drug. These parameters make it possible to predict the low
      solubility of olanzapine in the carriers (alone or in mixtures). Systems
      containing only Lutrol (also in the presence of Transcutol(r)) contain the drug
      in the form of particles of reduced size and in a crystalline form. Gelucire(r)
      44/14 apparently increases the amount of olanzapine dissolved in the solid
      carrier, but this is presumed to be a metastable state, probably related to the
      heterogeneous nature of the carrier that delays crystallization of the drug. The
      high hydrophilicity of the carriers proves suitable to an accelerated and quick
      release of the drug regardless of aging. Differences in the release profiles
      between Lutrol- and Gelucire-containing systems were interpreted in terms of the
      formation of polymer micelles by the Lutrols when in aqueous solution. 

PMID- 24300564
TI  - Terahertz pulsed imaging and magnetic resonance imaging as tools to probe
      formulation stability.
AB  - Dissolution stability over the entire shelf life duration is of critical
      importance to ensure the quality of solid dosage forms. Changes in the drug
      release profile during storage may affect the bioavailability of drug products.
      This study investigated the stability of a commercial tablet (Lescolr XL) when
      stored under accelerated conditions (40 oC/75% r.h.). Terahertz pulsed imaging
      (TPI) was used to investigate the structure of the tablet coating before and
      after the accelerated aging process. The results indicate that the coating was
      reduced in thickness and exhibited a higher density after being stored under
      accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI)
      of the water penetration processes during tablet dissolution in a USP-IV
      dissolution cell equipped with an in-line UV-vis analyzer was carried out to
      study local differences in water uptake into the tablet matrix between the
      stressed and unstressed state. The drug release profiles of the Lescolr XL tablet
      before and after the accelerated storage stability testing were compared using a
      "difference" factor ?1 and a "similarity" factor ?2. The results reveal that even
      though the physical properties of the coating layers changed significantly during
      the stress testing, the coating protected the tablet matrix and the densification
      of the coating polymer had no adverse effect on the drug release performance. 

PMID- 24300565
TI  - Preparation of Microcapsules Containing beta-Carotene with Thermo Sensitive
      Curdlan by Utilizing Reverse Dispersion.
AB  - We have tried to microencapsulate beta-carotene with curdlan of a thermogelation
      type polysaccharide. Microcapsules were prepared by utilizing reverse dispersion,
      in which salada oil was the continuous phase (O') and the curdlan water slurry
      (W) was the dispersed phase. beta-carotene (O) as a core material was broken into
      fine oil droplets in the dispersed phase to form the (O/W) dispersion. The (O/W)
      dispersion was poured in the continuous phase (O') and stirred to form the
      (O/W)/O' dispersion at room temperature and then, temperature of the dispersion
      was raised to 80  degrees C to prepare curdlan-microcapusles containing beta
      carotene. In this microencapsulation process, the concentrations of curdlan and
      oil soluble surfactant and the impeller speed to form the (O/W)/O' dispersion
      were mainly changed stepwise. We were able to prepare microcapsules by the
      microencapsulation method adopted here. The content of core material was
      increased with the curdlan concentration and decreased with the impeller speed
      and the oil soluble surfactant concentration. With the curdlan concentration, the
      drying rate of microcapsules was decreased and the retention ability for water
      was increased due to the stable preservation of beta-carotene. 

PMID- 24300562
TI  - Surface engineering of liposomes for stealth behavior.
AB  - Liposomes are used as a delivery vehicle for drug molecules and imaging agents.
      The major impetus in their biomedical applications comes from the ability to
      prolong their circulation half-life after administration. Conventional liposomes
      are easily recognized by the mononuclear phagocyte system and are rapidly cleared
      from the blood stream. Modification of the liposomal surface with hydrophilic
      polymers delays the elimination process by endowing them with stealth properties.
      In recent times, the development of various materials for surface engineering of
      liposomes and other nanomaterials has made remarkable progress. Poly(ethylene
      glycol)-linked phospholipids (PEG-PLs) are the best representatives of such
      materials. Although PEG-PLs have served the formulation scientists amazingly
      well, closer scrutiny has uncovered a few shortcomings, especially pertaining to
      immunogenicity and pharmaceutical characteristics (drug loading, targeting, etc.)
      of PEG. On the other hand, researchers have also begun questioning the biological
      behavior of the phospholipid portion in PEG-PLs. Consequently, stealth
      lipopolymers consisting of non-phospholipids and PEG-alternatives are being
      developed. These novel lipopolymers offer the potential advantages of structural
      versatility, reduced complement activation, greater stability, flexible handling
      and storage procedures and low cost. In this article, we review the materials
      available as alternatives to PEG and PEG-lipopolymers for effective surface
      modification of liposomes. 

PMID- 24300566
TI  - A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.
AB  - XK469 (NSC 697887) is a selective topoisomerase II beta inhibitor eliminated
      mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to
      investigate whether AOX1 genetic variation contributes to interindividual
      variability in XK469 clearance. Forty-one AOX1 single nucleotide polymorphisms
      (SNPs) and seven liver expression quantitative trait loci were genotyped in White
      patients with advanced refractory solid tumors (n=59) and leukemia (n=33). We
      found a significant decrease in clearance (tau=-0.32, P=0.003) in solid tumor
      patients with rs10931910, although it failed to replicate in the leukemia cohort
      (tau=0.18, P=0.20). Four other AOX1 SNPs were associated with clearance (P=0.01
      0.02) in only one of the two cohorts. Our study provides a starting point for
      future investigations on the functionality of AOX1 SNPs. However, variability in
      XK469 clearance cannot be attributed to polymorphisms in AOX1. 

PMID- 24300567
TI  - Management of arrhythmia syndromes during pregnancy.
AB  - PURPOSE OF REVIEW: To discuss the diagnosis and management of maternal
      arrhythmias occurring during pregnancy. RECENT FINDINGS: When necessary, current
      technology allows implantation of arrhythmia management devices and performing
      catheter ablation procedures with little or no risk from radiation exposure to
      the fetus. SUMMARY: A variety of cardiac rhythm disturbances can occur during
      pregnancy, ranging from benign ectopy to life-threatening arrhythmias. In
      patients with normal hearts and minimally symptomatic arrhythmias, only
      reassurance is necessary. The quality of the data on managing more serious
      arrhythmias in pregnancy is somewhat limited, yet with a clear understanding of
      the maternal hemodynamic changes associated with pregnancy, and the appropriate
      antiarrhythmic therapies available, almost all cases can be treated successfully.
      The decision to treat should be based on careful consideration of risk and
      benefits, yet, when therapy is deemed necessary, it should be administered
      promptly and with confidence. Drug therapy should be avoided during the first
      trimester if possible and drugs with the longest record of safety are preferred.
      The decision to pursue an invasive strategy is complicated by the potential for
      procedural risks. Yet, the state of modern technology is such that invasive
      strategies, when justified, can be carried out effectively.

PMID- 24300568
TI  - Peristaltic propulsion of generalized Burgers' fluids through a non-uniform
      porous medium: a study of chyme dynamics through the diseased intestine.
AB  - A mathematical study of the peristaltic flow of complex rheological viscoelastic
      fluids using the generalized fractional Burgers' model through a non-uniform
      channel is presented. This model is designed to study the movement of chyme and
      undigested chyme (biophysical waste materials) through the small intestine to the
      large intestine. To simulate blockages and impedance of debris generated by cell
      shedding, infections, adhesions on the wall and undigested material, a drag force
      porous media model is utilized. This effectively mimicks resistance to chyme
      percolation generated by solid matrix particles in the regime. The conduit
      geometry is mathematically simulated as a sinusoidal propagation with linear
      increment in shape of the bolus along the length of channel. A modified Darcy
      Brinkman model is employed to simulate the generalized flows through isotropic,
      homogenous porous media, a simplified but physically robust approximation to
      actual clinical situations. To model the rheological properties of chyme, a
      viscoelastic Burgers' fluid formulation is adopted. The governing equations are
      simplified by assuming long wavelength and low Reynolds number approximations.
      Numerical and approximate analytical solutions are obtained with two semi
      numerical techniques, namely the homotopy perturbation method and the variational
      iteration method. Visualization of the results is achieved with Mathematica
      software. The influence of the dominant hydromechanical and geometric parameters
      such as fractional viscoelastic parameters, wave number, non-uniformity constant,
      permeability parameter, and material constants on the peristaltic flow
      characteristics are depicted graphically. 

PMID- 24300569
TI  - Quality control of Platinum Spike dataset by probe-level mixed models.
AB  - Benchmark datasets are important for the validation and optimization of the
      analysis routes. Lately, a new benchmark dataset, 'Platinum Spike', for the
      Affymetrix GeneChip experiments has been introduced. We performed a quality check
      of the Platinum Spike dataset by using probe-level linear mixed models. The
      results have shown that there are 'empty' probe sets detecting transcripts,
      spiked in at different concentrations, and, reversely, there are probe sets that
      do not detect transcripts, spiked in at different concentrations, even though
      they were designed to do so. We proposed a formal inference procedure for testing
      the assumption of independence of all technical replicates in the data and
      concluded that for almost 10% of probe sets arrays cannot be treated
      independently, which has strong implications for the normalization procedures and
      testing for the differential expression. The proposed diagnostics procedure is
      used to facilitate a thorough exploration of gene expression Affymetrix data
      beyond the preprocessing and differential expression analysis. 

PMID- 24300570
TI  - Progestin priming before gonadotrophin stimulation and AI improves embryo
      development and normalises luteal function in the cat.
AB  - Exogenous gonadotrophins administered before AI can adversely alter endocrine
      dynamics and inhibit embryo development in felids. In the present study, we
      tested the hypothesis that priming the domestic cat ovary with progestin
      mitigates the negative influence of gonadotrophin therapy by normalising early
      embryogenesis and luteal function. Queens were given either: (1) progestin
      pretreatment plus chorionic gonadotrophins (n=8; primed); or (2) gonadotrophins
      only (n=8; unprimed). Ovulatory response was assessed laparoscopically, and cats
      with fresh corpora lutea (CL) were inseminated in utero. Ovariohysterectomy was
      performed 3 days later to recover intra-oviductal embryos for in vitro culture;
      one ovary was prepared for histology, and CL from the remaining ovary were
      excised and assessed for progesterone content and targeted gene expression. Of
      the six primed and seven unprimed queens inseminated, embryo(s) were recovered
      from five individuals per group. Embryos from progestin-primed donors more
      closely simulated normal stage in vivo development (P<0.05). No 2- or 4-cell
      embryos from either group developed beyond 16-cells in vitro; however, 50% of
      unprimed and 66.7% of primed (P>0.05) 5-16-cell embryos progressed to morulae or
      blastocysts by Day 4 of culture. Although histological characteristics were
      unaffected by progestin priming (P>0.05), luteal progesterone was unusually high
      (P<0.05) in unprimed compared with primed cats (72.4+/-5.8 vs. 52.2+/-5.5 ng mg(
      1), respectively). Two genes associated with progesterone biosynthesis
      (luteinising hormone receptor and 3beta-hydroxysteroid dehydrogenase) were
      upregulated in unprimed versus primed individuals (P=0.05 and P<0.05,
      respectively), indicating potential mechanistic pathways for the protective
      influence of pre-emptive progestin treatment. Building on earlier findings that
      progestin priming prevents spontaneous ovulation, increases ovarian sensitivity
      to gonadotrophins and ensures a normative endocrine environment, the present
      study demonstrates that pretreatment with this steroid also benefits embryo
      development and normalisation of early luteal function.

PMID- 24300571
TI  - [Surgical and endovascular treatment of lung arteriovenous malformations].
AB  - The article summarizes the experience of surgical treatment of 47 patients (1964
      2012 yy) with lung arteriovenous malformations (LAVM). Men were 29, women - 18.
      Age varied from 6 to 49 years. 20 patients had solitary lung arteriovenous
      malformations, the rest 27 had multiple malformations. Before 1983 the main
      diagnostic means was the angiopulmonography, since that the multyspiral computed
      tomography has been used. Before 1980 all patients received major surgical
      treatment, i.e., lobectomy (n=29), pneumonectomy (n=1) and 1 explorative
      thoracotomy. After 1980 the endovascular embolisation under the X-ray control
      took the leading place among the treatment options for these patients. 11
      patients had 17 embolisations; the lung resection was performed only in 3 cases.
      All negative outcomes (4 lethal and 8 complications) were registered before the
      1980. The were no lethal outcomes after the endovascular embolisation; only 3
      patients had complications. All patients demonstrated satisfactory and good
      outcomes, considering objective parameters and quality of life early and long
      after the endovascular embolisation. 

PMID- 24300572
TI  - [Endoscopic retrograde cholangiopancreaticography for the treatment of necrotic
      pancreatitis].
AB  - 40 patients with the acute necrotic pancreatitis and verified biliary
      hypertension were included in the study. During the endoscopic retrograde
      cholangiopancreaticography we avoided the main pancreatic duct contrast
      enhancement. The canulation during papillosphincterotomy (PST) was not used if
      the concrement was infringed in the ampulla. The use of these methods led to fast
      relief of the biliary hypertension and truthworthy positive dynamics of the
      disease course. The negative consequences were usually limited to transitory
      amilasemia and the pancreonecrosis progression was registered in only 4+/-4%
      cases. In comparison with cholecystostomy, the ERCP with PST showed better
      prognosis considering the frequency of septic complications and terms of hospital
      stay. The statistical analysis proved the the ERCP with PST are preferable to
      cholecystostomy in cases of pancreonecrosis with choledochlithiasis and biliary
      hypertension and the overall severity of pancreonecrosis is not higher than 11 by
      the physiological condition scale. 

PMID- 24300573
TI  - [Tetrahepaticojejunostomy for the treatment of the high biliary strictures].
AB  - The article highlights various techniques of biliodigestive anastomises, used for
      the treatment of high-level blockages of biliary ducts. The novel author method
      of tetrahepaticojejunostomy, possessing less insufficiency risk and less
      traumaticity was suggested. 38 patients have been operated on using the
      hepaticoenterostomy; 5 patients received the described method of
      tetrahepaticojejunostomy with positive outcome. 

PMID- 24300574
TI  - [Results of the laparoscopic cholecystectomy in elderly patients].
AB  - The results of 165 laparoscopic cholecystectomies were analyzed. All patients
      were divided into two groups according their age: the 1st group embrased patients
      from 60 years and older and the 2nd group included younger patients. The mean
      operative time was 89.5 min among the patients of the 1st group and 94.8 min
      among the patients of the 2nd group. For the 1st and 2nd groups, respectively,
      the overall hospital stay was 13.1+/-0.6 and 9.4+/-0.3 days; and the
      postoperative treatment lasted for 6.7+/-0.5 and 7.5+/-0.3 days, respectively.
      Complications were registered in 1.3 and 2.2% of patients, respectively. Thus,
      the results and outcomes of the laparoscopic cholecystectomy in elderly patients
      are comparable with those in younger contingent. 

PMID- 24300575
TI  - [Metabolic therapy at patients with a syndrome of diabetic foot].

PMID- 24300576
TI  - [Modern opportunities of abdominal sanation during the generalized purulent
      peritonitis].
AB  - Results of the treatment of generalized purulent peritonitis in 30 patients are
      presented. Based on the analysis of the performance of integrated assessment
      scales severity of the condition, the dynamics of change of bacterial
      contamination and microbiological landscape, and analysis of morbidity and
      mortality proved the effectiveness of intraperitoneal administration of the
      solution of dioxidin in patients with generalized purulent peritonitis. 

PMID- 24300577
TI  - [Ulcer disease: the state of art].

PMID- 24300578
TI  - [Surgical treatment of the metastatic invasion of the carotid artery by the
      tongue cancer].

PMID- 24300579
TI  - [The Plammer-Vinson syndrome].

PMID- 24300580
TI  - [The pheochromocytoma of the urinary bladder].

PMID- 24300581
TI  - [The gastrointestinal bleeding as a complication after cava-filter implantation].

PMID- 24300582
TI  - [The surgical treatment of the late recurrence of the colon cancer].

PMID- 24300583
TI  - [Clinical case of treatment patient with malignant carcinoid of the pancreas with
      liver metastases].

PMID- 24300584
TI  - Risk factors for inpatient venous thromboembolism despite thromboprophylaxis.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is the most common preventable cause
      of morbidity and mortality in the hospital. Adequate thromboprophylaxis has
      reduced the rate of hospital-acquired VTE substantially; however, some inpatients
      still develop VTE even when they are prescribed thromboprophylaxis. Predictors
      associated with thromboprophylaxis failure are unclear. In this study, we aimed
      to identify risk factors for inpatient VTE despite thromboprophylaxis. MATERIALS
      AND METHODS: We conducted a case-control study to identify independent predictors
      for inpatient VTE. Among patients discharged from the BJC HealthCare system
      between January 2010 and May 2011, we matched 94 cases who developed in-hospital
      VTE while taking thromboprophylaxis to 272 controls who did not develop VTE.
      Matching was done by hospital, patient age, month and year of discharge. We used
      multivariate conditional logistic regression to develop a VTE prediction model.
      RESULTS: We identified five independent risk factors for in-hospital VTE despite
      thromboprophylaxis: hospitalization for cranial surgery, intensive care unit
      admission, admission leukocyte count >13,000/mm(3), presence of an indwelling
      central venous catheter, and admission from a long-term care facility.
      CONCLUSIONS: We identified five risk factors associated with the development of
      VTE despite thromboprophylaxis in the hospital setting. By recognizing these high
      risk patients, clinicians can prescribe aggressive VTE prophylaxis judiciously
      and remain vigilant for signs or symptoms of VTE.

PMID- 24300585
TI  - Biochar-supported zerovalent iron for removal of various contaminants from
      aqueous solutions.
AB  - This work describes the synthesis and testing of a novel environmental sorbent
      that combines the advantages of biochar, chitosan, and zerovalent iron (ZVI).
      Chitosan was used as a dispersing and soldering reagent to attach fine ZVI
      particles onto bamboo biochar surfaces. Characterization of the resulted ZVI
      biochar composites (BBCF) indicated that chitosan effectively soldered the iron
      particles onto carbonaceous surfaces within the biochar pore networks. The BBCF
      showed enhanced ability to sorb heavy metals (Pb(II), Cr(VI), and As(V)),
      phosphate (P), and methylene blue (MB) from aqueous solutions. The removal of
      Pb(II), Cr(VI), and MB by the biochar-supported ZVI was mainly controlled by both
      the reduction and surface adsorption mechanisms. Removal of anionic contaminants
      (As(V) and P) was likely controlled by electrostatic attraction with the iron
      particles on the BBCF surfaces. An additional benefit is that the contaminant
      laden BBCF could be removed from aqueous solution easily by magnetic attraction. 

PMID- 24300586
TI  - Gradient echo quantum memory in warm atomic vapor.
AB  - Gradient echo memory (GEM) is a protocol for storing optical quantum states of
      light in atomic ensembles. The primary motivation for such a technology is that
      quantum key distribution (QKD), which uses Heisenberg uncertainty to guarantee
      security of cryptographic keys, is limited in transmission distance. The
      development of a quantum repeater is a possible path to extend QKD range, but a
      repeater will need a quantum memory. In our experiments we use a gas of rubidium
      87 vapor that is contained in a warm gas cell. This makes the scheme particularly
      simple. It is also a highly versatile scheme that enables in-memory refinement of
      the stored state, such as frequency shifting and bandwidth manipulation. The
      basis of the GEM protocol is to absorb the light into an ensemble of atoms that
      has been prepared in a magnetic field gradient. The reversal of this gradient
      leads to rephasing of the atomic polarization and thus recall of the stored
      optical state. We will outline how we prepare the atoms and this gradient and
      also describe some of the pitfalls that need to be avoided, in particular four
      wave mixing, which can give rise to optical gain. 

PMID- 24300588
TI  - Dithranol as a matrix for matrix assisted laser desorption/ionization imaging on
      a fourier transform ion cyclotron resonance mass spectrometer.
AB  - Mass spectrometry imaging (MSI) determines the spatial localization and
      distribution patterns of compounds on the surface of a tissue section, mainly
      using MALDI (matrix assisted laser desorption/ionization)-based analytical
      techniques. New matrices for small-molecule MSI, which can improve the analysis
      of low-molecular weight (MW) compounds, are needed. These matrices should provide
      increased analyte signals while decreasing MALDI background signals. In addition,
      the use of ultrahigh-resolution instruments, such as Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometers, has the ability to resolve
      analyte signals from matrix signals, and this can partially overcome many
      problems associated with the background originating from the MALDI matrix. The
      reduction in the intensities of the metastable matrix clusters by FTICR MS can
      also help to overcome some of the interferences associated with matrix peaks on
      other instruments. High-resolution instruments such as the FTICR mass
      spectrometers are advantageous as they can produce distribution patterns of many
      compounds simultaneously while still providing confidence in chemical
      identifications. Dithranol (DT; 1,8-dihydroxy-9,10-dihydroanthracen-9-one) has
      previously been reported as a MALDI matrix for tissue imaging. In this work, a
      protocol for the use of DT for MALDI imaging of endogenous lipids from the
      surfaces of mammalian tissue sections, by positive-ion MALDI-MS, on an ultrahigh
      resolution hybrid quadrupole FTICR instrument has been provided. 

PMID- 24300587
TI  - Impact of folic acid fortification on global DNA methylation and one-carbon
      biomarkers in the Women's Health Initiative Observational Study cohort.
AB  - DNA methylation is an epigenetic mechanism that regulates gene expression and can
      be modified by one-carbon nutrients. The objective of this study was to
      investigate the impact of folic acid (FA) fortification of the US food supply on
      leukocyte global DNA methylation and the relationship between DNA methylation,
      red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal
      women enrolled in the Women's Health Initiative Observational Study. We selected
      408 women from the highest and lowest tertiles of RBC folate distribution
      matching on age and timing of the baseline blood draw, which spanned the pre-
      (1994-1995), peri- (1996-1997), or post-fortification (1998) periods. Global DNA
      methylation was assessed by liquid chromatography-tandem mass spectrometry and
      expressed as a percentage of total cytosine. We observed an interaction (P =
      0.02) between fortification period and RBC folate in relation to DNA methylation.
      Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12
      vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%;
      P = 0.03) DNA methylation in the post-fortification period. We also observed
      significant correlations between one-carbon biomarkers and DNA methylation in the
      pre-fortification period, but not in the peri- or post-fortification period. The
      correlation between plasma homocysteine and DNA methylation was reversed from an
      inverse relationship during the pre-fortification period to a positive
      relationship during the post-fortification period. Our data suggest that (1)
      during FA fortification, higher RBC folate status is associated with a reduction
      in leukocyte global DNA methylation among postmenopausal women and; (2) the
      relationship between one-carbon biomarkers and global DNA methylation is
      dependent on folate availability. 

PMID- 24300589
TI  - Psychosocial and Adaptive Deficits Associated With Learning Disability Subtypes.
AB  - Children with specific learning disabilities (SLD) have deficits in the basic
      psychological processes that interfere with learning and academic achievement,
      and for some SLD subtypes, these deficits can also lead to emotional and/or
      behavior problems. This study examined psychosocial functioning in 123 students,
      aged 6 to 11, who underwent comprehensive evaluations for learning and/or
      behavior problems in two Pacific Northwest school districts. Using concordance
      discordance model (C-DM) processing strengths and weaknesses SLD identification
      criteria, results revealed working memory SLD (n = 20), processing speed SLD (n =
      30), executive SLD (n = 32), and no disability groups (n = 41). Of the SLD
      subtypes, repeated measures MANOVA results revealed the processing speed SLD
      subtype exhibited the greatest psychosocial and adaptive impairment according to
      teacher behavior ratings. Findings suggest processing speed deficits may be
      behind the cognitive and psychosocial disturbances found in what has been termed
      "nonverbal" SLD. Limitations, implications, and future research needs are
      addressed. 

PMID- 24300590
TI  - Handwriting analysis indicates spontaneous dyskinesias in neuroleptic naive
      adolescents at high risk for psychosis.
AB  - Growing evidence suggests that movement abnormalities are a core feature of
      psychosis. One marker of movement abnormality, dyskinesia, is a result of
      impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional
      methods for identifying movement abnormalities include observer-based reports and
      force stability gauges. The drawbacks of these methods are long training times
      for raters, experimenter bias, large site differences in instrumental apparatus,
      and suboptimal reliability. Taking these drawbacks into account has guided the
      development of better standardized and more efficient procedures to examine
      movement abnormalities through handwriting analysis software and tablet.
      Individuals at risk for psychosis showed significantly more dysfluent pen
      movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting
      kinematics offers a great advance over previous methods of assessing dyskinesia,
      which could clearly be beneficial for understanding the etiology of psychosis. 

PMID- 24300591
TI  - Oral polio vaccine response in breast fed infants with malnutrition and diarrhea.
AB  - Oral vaccines for polio (OPV) and rotavirus are less effective in children in the
      developing world. The reasons for this are not well understood. We tested for
      risk factors for poor response to OPV in infants from an urban slum of Dhaka,
      Bangladesh. Diminished serum neutralizing response to OPV, but not failure of
      intramuscularly administered vaccines, was associated with malnutrition,
      diarrhea, and shorter breastfeeding duration. Children with malnutrition (WAZ <
      2) had significantly lower OPV 3 titers (p=0.029). Children who had 2 or more
      diarrhea episodes during the 1st months of life were more than twice as likely to
      experience OPV failure as those who had 1 diarrhea episode or no diarrhea
      (p=0.0245). In contrast, each additional month in exclusive breastfeeding was
      associated with an increase in OPV 3 titer by 0.41 (p=0.0072) and 0.16 (p=0.0065)
      at the 25th and 50th percentiles of OPV 3 titers respectively. These data are
      consistent with a defect in induction of immunity in the gut for OPV but not
      parenteral vaccines, a defect that may be amenable to intervention in part via
      promotion of exclusive breastfeeding. 

PMID- 24300593
TI  - Twenty-five years of the WHO vaccines prequalification programme (1987-2012):
      lessons learned and future perspectives.
AB  - The World Health Organization (WHO) vaccines prequalification programme was
      established in 1987. It is a service provided to United Nations procurement
      agencies to ensure that the vaccines supplied through these agencies are
      consistently safe and effective under conditions of use in national immunization
      programmes. This review describes the purpose and aims of the programme, its
      evolution during 25 years of existence, its added value, and its role in the
      context of the WHO strategy to ensure the global availability of vaccines of
      assured quality. The rationale for changes introduced during the implementation
      of the programme is provided. The paper also discusses the resources involved,
      both human and financial, its performance, strengths and weaknesses and steps
      taken to maximize its efficiency. This historical perspective is used to inform
      proposed future changes to the service. 

PMID- 24300592
TI  - Immunogenic potential of latency associated antigens against Mycobacterium
      tuberculosis.
AB  - Tuberculosis remains a great health threat to the world among infectious diseases
      particularly with the advent of human immunodeficiency virus and emergence of
      drug resistant strains. In the light of the inconsistent efficacy imparted by the
      only currently available pre-exposure vaccine bacillus Calmette-Guerin BCG, the
      development of an improved TB vaccine is a very high international research
      priority. Vaccine candidates currently in clinical trials are also pre-exposure
      vaccines that aim to prevent active tuberculosis during an individual's lifetime.
      According to World Health Organization approximately a third of the world's
      population is latently infected with Mycobacterium tuberculosis. Dormancy or
      latency of Mycobacteria is associated with the formation of granuloma with poorly
      perfused interior leading to expression of genes which help them survive in this
      hostile environment. A group of about 50 genes belonging to the DosR regulon also
      known as latency antigens are expressed by Mycobacteria when they are persisting
      in the immuno-competent host. An understanding of the immunological effects
      produced by products of these latency induced genes may help in making a more
      potent vaccine. Incorporation of latency antigens into improved (live or subunit)
      vaccines may enhance the impact of these vaccines in which BCG priming can be
      followed by multisubunit protein boosting. These vaccines could act as post
      exposure vaccines for containment and prevention of latent TB activation. This
      heterologous boosting of BCG-primed immunity will be able to stimulate the known
      immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells
      (CD4(+) and CD8(+) T cells) mediated immune responses with cytokines such as IFN
      gamma and TNF-alpha? In our review we have analysed and compared the immunogenic
      potential of various latency-associated antigens of the DosR regulon in line with
      the current strategy of developing a recombinant post exposure booster vaccine. 

PMID- 24300594
TI  - Decreased immune response to pneumococcal conjugate vaccine after 23-valent
      pneumococcal polysaccharide vaccine in children.
AB  - BACKGROUND: Pneumococcal polysaccharide vaccine (PPV) is used in children at high
      risk of IPD. PPV is generally not considered to induce immunologic memory,
      whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody
      responses in infants and induce immunologic memory. Little is known about the
      characteristics of immune responses to PCV in children who previously received
      PCV and PPV in series. OBJECTIVE: To characterize immune responses to 13-valent
      pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F,
      9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent
      pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC),
      followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide
      vaccine (PPV23). METHODS: Children (n=89) who received PCV9-MnCC in infancy and
      PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were
      vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13
      (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity
      (OPA) were measured before and at 1 and 4 weeks postvaccination. RESULTS: One
      week postvaccination, IgG levels increased significantly for all serotypes in
      both groups, and >97% of vaccinees achieved IgG >=0.35MUg/ml 4 weeks after PCV13
      vaccination. The PCV9/PCV13 group had higher IgG responses compared with the
      PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the
      PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for
      serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported
      these findings. CONCLUSIONS: PPV23 vaccination of toddlers may compromise
      subsequent responses to pneumococcal conjugate vaccines. The clinical relevance
      of this finding is unclear.

PMID- 24300595
TI  - Effects of milk proteins and combined exercise training on aortic hemodynamics
      and arterial stiffness in young obese women with high blood pressure.
AB  - BACKGROUND: Obesity and reduced muscle strength are associated with increased
      blood pressure (BP). We examined the impact of milk proteins and combined
      exercise training (CET) on BP, arterial function, and muscle strength (one
      repetition maximum (1-RM)). METHODS: Thirty-three obese sedentary women (age = 30
      +/- 1 years; body mass index = 35.2 +/- 0.9 kg/m(2); systolic BP (SBP) = 129 +/-
      2 mm Hg) were randomized to control carbohydrate (n = 11), whey (n = 11), and
      casein (n = 11) supplementation for 4 weeks. All participants performed moderate
      intensity CET 3 days/week. Brachial and aortic SBP, augmentation index adjusted
      for 75 beats/minute (AIx@75), arterial stiffness (brachial-ankle pulse wave
      velocity (baPWV)), and 1-RM were measured before and after the interventions.
      RESULTS: There were significant (P < 0.05) time-by-group interactions for
      brachial SBP (bSBP), aortic SBP (aSBP), AIx@75, and baPWV. Whey and casein
      supplementation significantly (P < 0.05) decreased bSBP (approximately 5mm Hg for
      both), aSBP (approximately 7 mm Hg and approximately 6mm Hg, respectively),
      AIx@75 (approximately 9.2% and approximately 8.1%, respectively) and baPWV
      (approximately 57 cm/s and approximately 53 cm/s, respectively) compared with no
      changes in the control group. Upper- (approximately 22.2%) and lower-body 1-RM
      (approximately 44.0%) increased similarly in all groups. Changes in arterial
      function and 1-RM were not correlated. CONCLUSIONS: Milk protein supplementation
      with CET reduced SBP, wave reflection, and arterial stiffness in young obese
      women with prehypertension and hypertension. Because CET did not affect arterial
      function, milk proteins may have an antihypertensive effect by improving arterial
      function, as shown by reduced AIx@75 and baPWV. Muscle strength improvements
      after CET did not affect BP and arterial function. CLINICAL TRIAL REGISTRATION:
      ClinicalTrial.gov Registration NCT01830946.

PMID- 24300596
TI  - Clustering in Northern Territory perinatal data   for 2003-2005: implications for
      analysis and   interpretation.
AB  - Clustering in perinatal data can violate assumptions of independence, an
      important consideration for data analysis. Few published studies report on the
      extent of repeat births in routinely collected Australian perinatal data and the
      implications thereof for analysis and interpretation. This paper reports on a
      case study that examined the extent and implications of clustering in the
      Northern Territory Midwives Collection (NTMC) for the period 2003-2005. Data were
      obtained on 7,741 individual mothers giving birth to 8,707 babies in public
      hospitals during 2003-2005. Clusters of multiple pregnancies and repeat births
      were identified and the design effects for birth weight of Aboriginal and non
      Aboriginal newborns were calculated. Of the mothers, 46.1% were Aboriginal. Of
      these, 13.2% had repeat singleton births; 0.4% had multiple pregnancies, and 0.3%
      had both. Of non-Aboriginal mothers, 8.7% had repeat singleton births; 1.2% had
      multiple pregnancies; and 0.3% had both. The design effect was 1.07 for
      Aboriginal newborns and 1.04 for non-Aboriginal newborns. The design effects
      indicate that the correct variance accounting for clustering is 4-7% larger than
      the incorrect variance ignoring clustering when three consecutive years of NT
      data are considered and an intracluster correlation coefficient of 0.48 is
      assumed for birth weight between twin and non-twin siblings. Depending on the
      outcome of interest, the impact of clustering should be considered in
      multivariate analysis of perinatal data, especially when such analyses involve
      more than one year's data, include large proportions of Aboriginal mothers and
      newborns, and groups with different rates of repeat births.

PMID- 24300597
TI  - A vision-based self-calibration method for robotic visual inspection systems.
AB  - A vision-based robot self-calibration method is proposed in this paper to
      evaluate the kinematic parameter errors of a robot using a visual sensor mounted
      on its end-effector. This approach could be performed in the industrial field
      without external, expensive apparatus or an elaborate setup. A robot Tool Center
      Point (TCP) is defined in the structural model of a line-structured laser sensor,
      and aligned to a reference point fixed in the robot workspace. A mathematical
      model is established to formulate the misalignment errors with kinematic
      parameter errors and TCP position errors. Based on the fixed point constraints,
      the kinematic parameter errors and TCP position errors are identified with an
      iterative algorithm. Compared to the conventional methods, this proposed method
      eliminates the need for a robot-based-frame and hand-to-eye calibrations,
      shortens the error propagation chain, and makes the calibration process more
      accurate and convenient. A validation experiment is performed on an ABB IRB2400
      robot. An optimal configuration on the number and distribution of fixed points in
      the robot workspace is obtained based on the experimental results. Comparative
      experiments reveal that there is a significant improvement of the measuring
      accuracy of the robotic visual inspection system. 

PMID- 24300599
TI  - Simultaneous sampling of flow and odorants by crustaceans can aid searches within
      a turbulent plume.
AB  - Crustaceans such as crabs, lobsters and crayfish use dispersing odorant molecules
      to determine the location of predators, prey, potential mates and habitat.
      Odorant molecules diffuse in turbulent flows and are sensed by the olfactory
      organs of these animals, often using a flicking motion of their antennules. These
      antennules contain both chemosensory and mechanosensory sensilla, which enable
      them to detect both flow and odorants during a flick. To determine how
      simultaneous flow and odorant sampling can aid in search behavior, a 3
      dimensional numerical model for the near-bed flow environment was created. A
      stream of odorant concentration was released into the flow creating a turbulent
      plume, and both temporally and spatially fluctuating velocity and odorant
      concentration were quantified. The plume characteristics show close resemblance
      to experimental measurements within a large laboratory flume. Results show that
      mean odorant concentration and it's intermittency, computed as dc/dt, increase
      towards the plume source, but the temporal and spatial rate of this increase is
      slow and suggests that long measurement times would be necessary to be useful for
      chemosensory guidance. Odorant fluxes measured transverse to the mean flow
      direction, quantified as the product of the instantaneous fluctuation in
      concentration and velocity, v'c', do show statistically distinct magnitude and
      directional information on either side of a plume centerline over integration
      times of <0.5 s. Aquatic animals typically have neural responses to odorant and
      velocity fields at rates between 50 and 500 ms, suggesting this simultaneous
      sampling of both flow and concentration in a turbulent plume can aid in source
      tracking on timescales relevant to aquatic animals. 

PMID- 24300600
TI  - PANI and graphene/PANI nanocomposite films--comparative toluene gas sensing
      behavior.
AB  - The present work discusses and compares the toluene sensing behavior of
      polyaniline (PANI) and graphene/polyaniline nanocomposite (C-PANI) films. The
      graphene-PANI ratio in the nanocomposite polymer film is optimized at 1:2. For
      this, N-methyl-2-pyrrolidone (NMP) solvent is used to prepare PANI-NMP solution
      as well as graphene-PANI-NMP solution. The films are later annealed at 230 
      degrees C, characterized using scanning electron microscopy (SEM) as well Fourier
      transform infrared spectroscopy (FTIR) and tested for their sensing behavior
      towards toluene. The sensing behaviors of the films are analyzed at different
      temperatures (30, 50 and 100  degrees C) for 100 ppm toluene in air. The
      nanocomposite C-PANI films have exhibited better overall toluene sensing behavior
      in terms of sensor response, response and recovery time as well as repeatability.
      Although the sensor response of PANI (12.6 at 30  degrees C, 38.4 at 100  degrees
      C) is comparatively higher than that of C-PANI (8.4 at 30  degrees C, 35.5 at 100
      degrees C), response and recovery time of PANI and C-PANI varies with operating
      temperature. C-PANI at 50  degrees C seems to have better toluene sensing
      behavior in terms of response time and recovery time. 

PMID- 24300602
TI  - [Predicting the risk of septic and necrotic complications in femoral amputation
      stump].
AB  - Treatment results of 430 patients with ischemic gangrene of lower limbs were
      analyzed and major risk factors of postoperative complications considering the
      femoral amputation stump were outlighted. These are: the high level of artery
      occlusion, ligature muscle compression in the stump, absence of active drainage
      and elderly age (more than 80 years), anemia. The intraoperative use of laser
      Doppler flowmetry gives the possibility to assess the potential viability of
      muscles at the amputation level. Predicting the risk of local postoperative
      complications allowed the differential approach to the stump formation and
      improved the treatment results. 

PMID- 24300601
TI  - Nav 1.5 mutations linked to dilated cardiomyopathy phenotypes: Is the gating pore
      current the missing link?
AB  - Nav 1.5 dysfunctions are commonly linked to rhythms disturbances that include
      type 3 long QT syndrome (LQT3), Brugada syndrome (BrS), sick sinus syndrome (SSS)
      and conduction defects. Recently, this channel protein has been also linked to
      structural heart diseases such as dilated cardiomyopathy (DCM).

PMID- 24300604
TI  - [Pulmonary and pleural complications of the descending aorta surgery].
AB  - The experience of surgical treatment of 84 patients with diseases of the
      descending thoracic aorta was analyzed. Frequency and structure of pleura
      pulmonary complications after reconstructive surgery of the descending aorta were
      thoroughly registered. 58.3% of the operated patints developed complications. The
      most frequent complication was the acute respiratory insufficiency in early
      postoperative period (29.76% of patients). 

PMID- 24300603
TI  - [The role of vascular surgery in the multidisciplinary approach to the diabetic
      foot syndrome].
AB  - The efficacy of the percutaneous transluminal balloon angioplasty in patients
      with critical ischemia of the lower limbs and diabetes mellitus was analyzed. The
      study included 102 patients with septic complications of the diabetic foot
      syndrome. The main group consisted of 37 patients, who received both the
      traditional conservative therapy and the endovascular angioplasty. The study
      proves that the endovascular interventions by diabetic foot syndrome are
      effective and justified. Revascularisation permits the minimal resectional
      interventions on the foot, stop the ischemia and minimize the number of repeated
      necrectomies and high amputations. The diabetic foot syndrome is represented as a
      multidisciplinary problem. 

PMID- 24300605
TI  - [The analysis of perioperative period in patients with lung cancer stage III,
      receiving the combined treatment].
AB  - The intra- and postoperative period was analyzed in 202 patients with non-small
      cell lung carcinoma, treated with the combined therapy and intraoperative
      radiotherapy. There were no intraoperative complications registered, in spite of
      complex antitumor treatment. 18.8% of patients developed postoperative
      complications, which has no substantial influence on the outcome and were
      determined by the volume of the operation. The postoperative lethality rate was
      3.0%. 

PMID- 24300606
TI  - [The choice of surgical access in the treatment of lung hydatidosis in children].
AB  - Thoracoscopic and traditional access for the treatment of lung hydatidosis in
      children was compared. 56 children, who composed the 1st (control) group, were
      operated on with the open access. The 2nd (main) group, consisted of 22 patients,
      operated on thoracoscopically. The issue holds the thorough description of the
      operative technique. The mean operative time was 61.2+/-7.4 min for the
      thoracoscopic operation, the mean pleural drainig time was 2.5+/-0.7 days. The
      mean postoperative hospital stay was 12+/-3.5 days. For the patients of the
      control group, the operative time was 86.4+/-25.2 min, draining time was 4+/-1.2
      days and hospital stay was 18.4+/-8.2 days. There were no conversion cases. 3
      patients of the "thoracoscopic" group developed postoperative pneumonia and
      bronchial fistula. Considering the strict following the principles of
      antiparasitic treatment, the endoscopic treatment of lung hydatidosis proved to
      be a method of choice for the surgical treatment of lung hydatidosis in children.

PMID- 24300607
TI  - [The choice of resection volume by the combination of perforative duodenal ulcer
      with other complications of the ulcer disease].
AB  - Treatment results of 59 patients with the complicated ulcer disease were
      analyzed. Authors prove, that in cases of perforative duodenal ulcer, the
      operation should aim the treatment of all the complications. The use of 2/3
      gaster resection in combination with Jadd pyloroplasty and trunk vagotomy led to
      the decrease of the lethality rate on 21%. 

PMID- 24300608
TI  - [The minilaparotomy cholecystectomy in patients with calculous cholecystitis].
AB  - The article presents the results of surgical treatment of 596 patients with
      cholelithiasis, operated with minilaparotomy access. Good results were obtained
      in 93% of patients with chronic calculous cholecystitis, as well as acute
      inflammation. This access is provided a low number of intraoperative and
      postoperative complications. In addition, the minimal access allows to extend, if
      necessary, the intervention and control the complications. 

PMID- 24300609
TI  - [The efficacy of the moisture and warmed CO(2) for laparoscopic surgery].
AB  - A prospective, randomized study comparing 150 patients undergoing laparoscopic
      operations (110 patients undergoing laparoscopic cholesystectomy and 40 patients
      laparoscopic fundoplication) with standard CO2 insufflation vs those receiving
      warmed, humidified CO2 was performed. All patients were randomized into 2 groups 
      84 receiving standard CO2 insufflation (control group) and 66 receiving warmed,
      humidified CO2 (main group). Main variables included patient core temperature,
      postoperative pain, analgesic requirements and other postoperative dates. We
      revaeled that warmed, humidified CO2 has advantages that were statistically
      significant. Patients undergoing warmed, humidified carbon dioxide (CO2)
      insufflation for maintain a warmer intraoperative core temperature, and have less
      postoperative pain and need less analgesic requirements than patients with
      standard CO2 insufflation. 

PMID- 24300610
TI  - [Hybrid surgery for the treatment of ovarial cysts in newborns].
AB  - The aim of this study was to evaluate the effect of hybrid technology
      (laparoscopy and open surgery) for treatment of ovarian cysts in small babies and
      infants. Between January 2002 and November 2012, we have performed 11 operation
      for neonatal ovarian cysts repaired through standard circumumbilical incision
      (Group I) and 16 operation with using combined hybrid laparoscopic-assisted
      technique (Group II). The circumumbilical incision utilized at our institution is
      a classic Bianchi procedure. The hybrid approach combined 2 technique -
      laparoscopic and open. The trocar for optic telescope was inserted through a
      circumumbilical incision. The one working instrument was introduced into the
      peritoneal cavity direct through umbilicus. Afterwords, ovarian cyst was deflated
      with using transabdominal needle aspiration, delivered by an extended umbilical
      incision and enucleated as in standard open surgery. The two groups were compared
      for patients demographics, operative report and early postoperative outcomes. All
      procedures were performed successfully with no complications rate. There were no
      differences in the preoperative parameters between the two groups. The
      differences between groups for operative and postoperative results were
      statistically significant (p<0.05). The mean operative time in Group I was 30.91
      min. In contrast, the mean duration of the operation in the Group II was 21.56
      min. The mean time to beginning and time of full enteral feeding for patients
      with hybrid approach were significantly shorter as for patients with umbilical
      incision (4.06 hours vs 10.91 hours; 13 hours vs 20.55 hours). Prolonged mean
      postoperative hospital stay were registered in patients of the Group I (6.36 days
      vs 3.19 days; p<0.05). The postoperative course and follow up was uneventful in
      the all patients. The experience described in this study confirms that hybrid
      operation can be applied for treatment of neonatal ovarian cysts with outcomes
      better than standard open surgery. 

PMID- 24300611
TI  - [Postoperative intestinal paresis: the problem of abdominal surgery].

PMID- 24300612
TI  - [Comparative efficacy of dioksidin and chlorhexidine in the local treatment of
      phlegmons of different localization].

PMID- 24300613
TI  - [Migration of the esophageal stent as a reason of the ileal obstruction].

PMID- 24300614
TI  - [The ischemic necrosis of the gastric stump after distal gastric resection].

PMID- 24300615
TI  - [Surgical treatment of the pulmonary embolism].

PMID- 24300616
TI  - [Transanal endoscopic operations in the complex treatment of the complicated
      colorectal cancer].

PMID- 24300617
TI  - [The advantages of the short intensive training course in endoscopic surgery].
AB  - The advantages of one-day training courses on the example of the short intensive
      course "manual suture in endoscopic surgery" are represented. The programme
      consists of the short 8-hours course, including theoretic lectures, practice
      seminars, virtual trainings and the trainee's self work under the control of the
      experienced supervisors. The preliminary assessment of the course, performed with
      the use of questionnaires and testing in small groups, showed it's unarguable
      efficacy for surgeons. 

PMID- 24300618
TI  - [The training concept of laparoscopic surgery in post-graduate education of
      doctors].
AB  - The active use of virtual devices and laparoscopic boxes for the control of the
      achieved skills level are the general idea of the suggested concept of the
      laparoscopic surgical training. The in vivo training make sense only after
      finishing the "virtual" course. The complete realization of these new concept of
      laparoscopic surgery training is possible only in frames of the endoscopic
      surgery department of the mighty hospital center. The organization of such center
      promise to rise the level of doctors' training. 

PMID- 24300619
TI  - Measurement of esophageal pressure at bedside: pros and cons.
AB  - PURPOSE OF REVIEW: Esophageal pressure measurement well estimates pleural
      pressure. The interpretation of absolute values is often debated for various
      reasons, but the changes in pressure measured are considered very accurate
      provided that a number of precautions are taken. The information provided by
      these measurements is unique in nature and has an enormous potential to influence
      management. It allows to study the exact influence of the chest wall and to
      determine the real lung distending pressure. It is also the only way to quantify
      respiratory muscle activity and the work of breathing. RECENT FINDINGS: The
      application of esophageal pressure monitoring potentially covers a large field,
      especially for what concerns mechanical ventilation. This goes from the acute
      phase of the acute respiratory distress syndrome (ARDS) to weaning and patient
      ventilator interactions. During ARDS, recent findings indicate that this
      measurement may help titrating the level of positive end-expiratory pressure or
      to determine the well tolerated upper limit of airway pressure. SUMMARY:
      Application of esophageal pressure monitoring is limited by technical issues, the
      need for background physiological knowledge and the fact that very few studies
      have assessed a direct influence of this measurement on patients' outcome. The
      technique is underused in everyday practice.

PMID- 24300620
TI  - Cell-based therapies for the acute respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: Acute respiratory distress syndrome (ARDS) is a multifaceted
      lung disease with no current effective therapy. Many clinical trials using
      conventional pharmacologic therapies have failed, suggesting the need to examine
      alternative approaches. Thus, attention has focused on the therapeutic potential
      of cell-based therapies for ARDS, with promising results demonstrated in relevant
      preclinical disease models. We review data concerning the therapeutic promise of
      cell-based therapies for ARDS. RECENT FINDINGS: Recent experimental studies
      provide further evidence for the potential of cell-based therapies in ARDS. A
      number of cell types, particularly mesenchymal stem/stromal cells (MSCs), bone
      marrow-derived mononuclear cells, endothelial progenitor cells, and embryonic
      stem cells have been demonstrated to reduce mortality and modulate the
      inflammatory and remodeling processes in relevant preclinical ARDS models.
      Multiple insights have emerged in regard to the mechanisms by which cell
      therapies - particularly MSCs - exert their effects, with evidence supporting
      direct cell-mediated and paracrine-mediated mechanisms of action. Diverse
      paracrine mechanisms exist, including the release of cytokines, growth factors
      (such as keratinocyte growth factor), and antimicrobial peptides, and transfer of
      cellular contents such as peptides, nucleic acids, and mitochondria via either
      microvesicular or direct cell-cell contact-mediated transfer. SUMMARY: Cell-based
      therapies offer considerable promise for the treatment of ARDS. While MSC-based
      therapies are being rapidly advanced toward clinical testing, clear therapeutic
      potential exists for other cell types for ARDS. A greater understanding of
      current knowledge gaps should further enhance the therapeutic potential of cell
      based therapies for ARDS.

PMID- 24300621
TI  - Epithelial and endothelial damage induced by mechanical ventilation modes.
AB  - PURPOSE OF REVIEW: The adult respiratory distress syndrome (ARDS) is a common
      cause of respiratory failure with substantial impact on public health. Patients
      with ARDS generally require mechanical ventilation, which risks further lung
      damage. Recent improvements in ARDS outcomes have been attributed to reductions
      in deforming stress associated with lung protective mechanical ventilation modes
      and settings. The following review details the mechanics of the lung parenchyma
      at different spatial scales and the response of its resident cells to deforming
      stress in order to provide the biologic underpinnings of lung protective care.
      RECENT FINDINGS: Although lung injury is typically viewed through the lens of
      altered barrier properties and mechanical ventilation-associated immune
      responses, in this review, we call attention to the importance of heterogeneity
      and the physical failure of the load bearing cell and tissue elements in the
      pathogenesis of ARDS. Specifically, we introduce a simple elastic network model
      to better understand the deformations of lung regions, intra-acinar alveoli and
      cells within a single alveolus, and consider the role of regional distension and
      interfacial stress-related injury for various ventilation modes. SUMMARY:
      Heterogeneity of stiffness and intercellular and intracellular stress failure are
      fundamental components of ARDS and their development also depends on the
      ventilation mode.

PMID- 24300622
TI  - A cost-effective strategy for primary prevention of acute rheumatic fever and
      rheumatic heart disease in children with pharyngitis.
AB  - Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease
      (RHD) in children depends on prompt and effective diagnosis and treatment of
      pharyngitis at the primary level of care. Cost-effectiveness modeling shows that
      the most cost-effective strategy for primary prevention in South Africa (SA) is
      to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis
      in children presenting at the primary level of care and then to treat them with a
      single dose of intramuscular penicillin. Treat All and CDR2+ strategies are
      affordable and simple and miss few cases of streptococcal pharyngitis at the
      primary level of care. The CDR2+ strategy is the most cost-effective for primary
      prevention of ARF and RHD in urban SA and should complement primordial and
      secondary prevention efforts. 

PMID- 24300623
TI  - From 'stepchild of primary healthcare' to priority programme: lessons for the
      implementation of the National Integrated School Health Policy in South Africa.
AB  - In this article, I explore the South African 2003 National School Health Policy
      (NSHP) and the revised 2012 Integrated School Health Policy (ISHP). I examine
      whether the shortcomings in the development, content and implementation of the
      2003 NSHP, and the context in which it was implemented, have been addressed
      adequately in the 2012 ISHP. The shortcomings include poorly structured
      relationships among key policy actors; an absent policy translation process
      resulting in insufficient understanding and prioritisation of school health by
      district and facility managers; and poor support and training of nurses.
      Insufficient capacity and resources, compounded by inadequate referral service
      capacity, resulted in the inequitable coverage and quality of the service and
      caused nurses to refer to school health as 'the stepchild of primary healthcare'.
      The comparison of the 2003 and 2012 policies is guided by the policy analysis
      framework of the Walt and Gilson policy triangle, which considers the policy
      context, process of policy development, policy actors and the policy content as
      key dimensions to successful policy development and implementation. I draw on an
      evaluation of a six-year implementation period (2003 - 2009) of the 2003 NSHP,
      which revealed the implementation challenges with the related explanatory
      factors. I provide lessons from the evaluation of the 2003 NSHP, highlight the
      policy changes in the new 2012 ISHP and finally highlight key opportunities, and
      remaining challenges, for the implementation of the new 2012 ISHP.  

PMID- 24300624
TI  - Developing generalism in the South African context.
AB  - The largest impact on the South African burden of disease will be made in
      community-based and primary healthcare (PHC) settings and not in referral
      hospitals. Medical generalism is an approach to the delivery of healthcare that
      routinely applies a broad and holistic perspective to the patient's problems and
      is a feature of PHC. A multi-professional team of generalists, who share similar
      values and principles, is needed to make this a reality. Ward-based outreach
      teams include community health workers and nurses with essential support from
      doctors. Expert generalists - family physicians - are required to support PHC as
      well as provide care at the district hospital. All require sufficient training,
      at scale, with greater collaboration and integration between training programmes.
      District clinical specialist teams are both an opportunity and a threat. The
      value of medical generalism needs to be explained, advocated and communicated
      more actively.  

PMID- 24300625
TI  - Warfarin in non-valvular atrial fibrillation.
AB  - The development of novel oral anticoagulants that are effective alternatives to
      warfarin in non-valvular atrial fibrillation (AF) is a welcome advance. However,
      a variety of unresolved problems with their use, and not least with their cost,
      make it important to re-evaluate the use of warfarin as it will likely remain the
      anticoagulant of choice in South African patients with non-valvular AF for the
      foreseeable future. In this article, we review the correct clinical use of
      warfarin. Guidance is provided on commencing warfarin treatment, maintenance
      dosing, the recommended steps when temporary withdrawal of treatment is
      necessary, the management of bleeding, and the use of warfarin in chronic kidney
      disease. Techniques for changing from warfarin to one of the new oral
      anticoagulants and vice versa are included.  

PMID- 24300626
TI  - A comparison of the pharmacokinetics of Aspen Ceftriaxone and Rocephin in
      community-acquired meningitis.
AB  - BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening
      condition that is common among immunocompromised individuals. Intravenous
      ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as
      first-line therapy in South Africa. Despite concerns regarding therapeutic
      equivalence with generic agents, this is the first study that has been conducted
      comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation
      with the originator. OBJECTIVE: To compare the PK and safety of Aspen Ceftriaxone
      (AC) and ROC in the treatment of adult CABM.Methods. A total of 63 eligible
      patients were randomised 1:1 to receive 2 g of either medication twice daily for
      a duration based on the identity of the causative organism and their physician's
      clinical judgment. The primary endpoint of this study was the comparison of
      clinical PK, specifically the concentrations of each drug in the cerebrospinal
      fluid with corresponding paired plasma samples. While this study was underpowered
      to assess efficacy, safety could be evaluated on the basis of reported adverse
      events. RESULTS: The two patient groups were epidemiologically similar. There
      were no statistically significant differences in PK between either agent, nor any
      difference with regard to safety. CONCLUSION: AC can be considered as equivalent
      to ROC with regard to PK and safety in patients with CABM.

PMID- 24300627
TI  - Poverty, AIDS and child health: identifying highest-risk children in South
      Africa.
AB  - BACKGROUND: Identifying children at the highest risk of negative health effects
      is a prerequisite to effective public health policies in Southern Africa. A
      central ongoing debate is whether poverty, orphanhood or parental AIDS most
      reliably indicates child health risks. Attempts to address this key question have
      been constrained by a lack of data allowing distinction of AIDS-specific parental
      death or morbidity from other causes of orphanhood and chronic illness.
      OBJECTIVES: To examine whether household poverty, orphanhood and parental illness
      (by AIDS or other causes) independently or interactively predict child health,
      developmental and HIV-infection risks. METHODS: We interviewed 6 002 children
      aged 10 - 17 years in 2009 - 2011, using stratified random sampling in six urban
      and rural sites across three South African provinces. Outcomes were child mental
      health risks, educational risks and HIV-infection risks. Regression models that
      controlled for socio-demographic co-factors tested potential impacts and
      interactions of poverty, AIDS-specific and other orphanhood and parental illness
      status. RESULTS: Household poverty independently predicted child mental health
      and educational risks, AIDS orphanhood independently predicted mental health
      risks and parental AIDS illness independently predicted mental health,
      educational and HIV-infection risks. Interaction effects of poverty with AIDS
      orphanhood and parental AIDS illness were found across all outcomes. No effects,
      or interactions with poverty, were shown by AIDS-unrelated orphanhood or parental
      illness. CONCLUSIONS: The identification of children at highest risk requires
      recognition and measurement of both poverty and parental AIDS. This study shows
      negative impacts of poverty and AIDS-specific vulnerabilities distinct from
      orphanhood and adult illness more generally. Additionally, effects of interaction
      between family AIDS and poverty suggest that, where these co-exist, children are
      at highest risk of all.

PMID- 24300628
TI  - Resource implications of adopting a restrictive neonatal blood transfusion
      policy.
AB  - BACKGROUND: Blood transfusions (BTFs) are not without risk and pose a significant
      financial burden on resource-limited services. In line with current international
      evidence, the nursery at Groote Schuur Hospital (GSH), Cape Town, South Africa,
      introduced a restrictive BTF protocol to minimise transfusions and manage costs.
      OBJECTIVE: To determine whether adopting a restrictive BTF policy results in
      fewer transfusions. METHODS: Data were retrospectively collected on all infants
      who received BTFs in the GSH nursery over a 6-month period following adoption of
      a restrictive BTF policy in 2010. BTF figures for a similar time period before
      the restrictive policy, during 2008, were obtained for comparison. RESULTS: After
      introduction of the restrictive BTF policy, 42 of 1 097 infants admitted (3.8%)
      received a total of 64 BTFs. In comparison, 102 of a total of 940 infants (10.9%)
      admitted during a period of the same length before introduction of the
      restrictive BTF policy received a total of 121 transfusions. Comparison between
      the number of BTFs administered before and after the restrictive policy showed a
      highly statistically significant difference (p<0.001). The total cost of the
      blood products used in the two 6-month periods was R91 870 v. R48 640, based on
      current prices. CONCLUSIONS: By adopting a restrictive policy, we were able to
      halve the number of BTFs, reduce risks associated with transfusions, and achieve
      significant cost benefits. Following evidence-based guidelines results in high
      standards of care, while also making the most effective use of resources.

PMID- 24300629
TI  - Blood cultures in sick children.
AB  - BACKGROUND: Blood cultures (BCs) are frequently performed in sick children. A
      recent audit of BCs among adult patients documented high rates of contamination
      by coagulase-negative staphylococci (CoNS). OBJECTIVES: To describe BC
      contamination rates and common pathogenic organisms causing bloodstream infection
      in children at a tertiary- level children's hospital. METHODS: BC results for
      children admitted to Red Cross War Memorial Children's Hospital from 2008 to 2012
      were extracted from the National Health Laboratory Service database. Pathogenic
      and non-pathogenic (contaminated) growth on BCs in children <1 year of age and >1
      year of age, were analysed. Data analysis was performed using Epi Info version
      3.5.1. RESULTS: A total of 47 677 BCs were performed in the 5-year period. The
      proportion of contaminated specimens ranged between 5.9% and 7.2% per year
      (p=0.4). CoNS was the predominant isolate in 53.8% of all contaminated BCs.
      Children <1 year of age experienced higher contamination rates than children >1
      year of age (8.7% v. 4.7%; relative risk 1.84; 95% confidence interval (CI) 1.71 
      1.97). Pathogenic organisms were isolated in 6.2% (95% CI 6.0 - 6.4) of all BC
      specimens. Among Gram-positive organisms, the proportion of Streptococcus
      pneumoniae isolates declined from 14.3% to 4.7% (p<0.00001), while there was a
      significant increase in Gram-negative organisms (51.8% - 57.9%; p=0.04) over the
      5-year period. Klebsiella pneumoniae, the predominant Enterobacteriaceae
      isolated, decreased from 45.8% to 31.7% (p=0.004). CONCLUSION: This study
      identified unacceptably high BC contamination rates, emphasising the importance
      of collecting BC specimens under sterile conditions.

PMID- 24300630
TI  - Effectiveness of sequential v. standard triple therapy for treatment of
      Helicobacter pylori infection in children in Nairobi, Kenya.
AB  - BACKGROUND: Once the diagnosis of Helicobacter pylori is confirmed, treatment
      requires at least two antibiotics and an acid inhibitor for a minimum of seven
      days. Unfortunately, treatment failures are being frequently reported. Treatment
      regimens that include sequential administration of antibiotics with acid
      inhibitors have been developed to try and increase the rate of eradication.
      OBJECTIVE: To determine the effectiveness of a novel 10-day sequential therapy
      compared with the standard 10-day triple therapy for treatment of H. pylori
      infection in children. METHODS: A double-blinded, randomised, controlled trial
      was conducted. Children under the age of 16 years with recurrent abdominal pain
      associated with dyspepsia and diagnosed with H. pylori by histology were randomly
      allocated either to a 10-day sequential treatment regimen or to a 10-day
      conventional triple therapy. Analysis of the outcome of this study was based on
      clinical improvement and confirmed H. pylori eradication based on stool H. pylori
      antigen detection and/or repeat endoscopy. RESULTS: Of the 71 patients included
      in the analysis, 45 (63.4%) were given the 10-day conventional treatment while 26
      (36.6%) received the 10-day sequential treatment. There was no difference in
      clinical improvement after treatment in the two therapies. However, there was a
      significant difference in the eradication of H. pylori between the conventional
      v. sequential regimens (48.8% v. 84.6%, respectively; p=0.02, odds ratio 0.19).
      CONCLUSION: The sequential treatment had a significantly higher H. pylori
      eradication rate than the conventional treatment.

PMID- 24300631
TI  - Combined paediatric liver-kidney transplantation: analysis of our experience and
      literature review.
AB  - BACKGROUND: Renal insufficiency is increasingly common in end-stage liver disease
      and allocation of livers to this category of patient has escalated. The frequency
      of combined liver-kidney transplantation (CLKT) has consequently increased.
      Indications for CLKT in children differ from those for adults and typically
      include rare congenital conditions; subsequently limited numbers of this
      procedure have been performed in paediatric patients worldwide. Scant literature
      exists on the subject. METHODS: Subsequent to institutional approval, a
      retrospective chart analysis of all paediatric CLKTs performed at the Transplant
      Unit, Wits Donald Gordon Medical Centre, University of the Witwatersrand,
      Johannesburg, South Africa between January 2005 and July 2013 was conducted.
      RESULTS: Defining children as younger than 18 years of age, 43 patients had
      received a liver transplant since 2005, of whom 8 received a CLKT. Indications
      included autosomal recessive polycystic kidney disease (n=3), primary
      hyperoxaluria type 1 (n=4) and heterozygous factor H deficiency with atypical
      haemolytic uraemic syndrome (n=1). Graft combinations included whole liver and
      one kidney (n=5), whole liver and two kidneys (n=1) and left lateral liver
      segment and one kidney (n=2), all from deceased donors. Patient age ranged from 4
      to 17 years (median 9) and included 4 females and 4 males. Weight ranged from 13
      to 42 kg (median 22.5). We describe one in-hospital mortality. The remaining 7
      patients were long-term survivors with a survival range from 6 to 65 months.
      CONCLUSIONS: Although rarely indicated in children, CLKT is an effective
      treatment option, appropriately utilising a scarce resource and significantly
      improving quality of life in the recipient.

PMID- 24300632
TI  - Internship training adequately prepares South African medical graduates for
      community service - with exceptions.
AB  - BACKGROUND: The 2-year internship period for medical graduates began in South
      Africa in 2005 and has never been formally evaluated. OBJECTIVE: This study
      assessed the perceptions of community service medical officers (COSMOs) working
      at district hospitals (DHs) in KwaZulu-Natal (KZN) to determine whether the 2
      year internship programme had adequately prepared them for community service
      (CS). METHOD: A cross-sectional descriptive study was conducted regarding the
      perceptions of COSMOs working at 22 district hospitals in KZN. Data were
      collected in July 2012, using a questionnaire based on the core skills and
      knowledge detailed in the Health Professions Council of South Africa intern log
      book. All eight domains were self-assessed and a score of 4 out of 5 indicated an
      ability to work independently. RESULTS: Of the COSMOs, 78% (60 out of 89)
      completed the questionnaire. Most felt well-prepared for CS in all disciplines,
      but critical gaps in knowledge and skills were identified in paediatrics,
      orthopaedics, anaesthetics and obstetrics. In addition, 75% of respondents (45
      out of 60) expressed a need for additional training in the disciplines of ear,
      nose and throat (ENT), urology, ophthalmology and dermatology. CONCLUSION: The 2
      year internship has provided the basis for independent medical practice in DHs.
      However, certain critical skill gaps need urgent attention, particularly in
      obstetrics and anaesthesia. Areas of weakness in ENT, urology, ophthalmology and
      dermatology could be addressed by including these specialities as a compulsory
      rotation in surgery, medicine or family medicine during internship training.

PMID- 24300633
TI  - A follow-up cross-sectional study of environmental lead exposure in early
      childhood in urban South Africa.
AB  - BACKGROUND: Lead exposure has significant detrimental effects on the health and
      wellbeing of children. In resource-poor countries, information on the extent of
      lead exposure is often inadequate owing to the lack of surveillance and screening
      programmes. OBJECTIVE: To determine the degree of lead exposure in children
      residing in South African urban areas. METHODS: A cross-sectional survey was
      conducted in schools in Johannesburg, Cape Town and Kimberley in 2007 - 2008.
      Blood lead levels were assessed in a total of 1 349 grade 1 children using the
      LeadCare Analyser system. Parents completed a structured questionnaire on
      sociodemographic profiles and risk factors to provide information about
      socioeconomic status and other risk factors for lead exposure. RESULTS: Blood
      lead levels ranged from 0.8 - 32.3 MUg/dl. The mean blood lead level in the total
      sample was 7.97 MUg/dl; 74% had blood lead levels >=5 MUg/dl. The highest
      proportion (84%) of children with blood lead levels >=5 MUg/dl was in
      Johannesburg. In the multivariate analysis, socioeconomic status was
      significantly associated with blood lead levels >=5 MUg/dl. CONCLUSION: Lead
      exposure in South African urban areas remains widespread. The risk of lead
      poisoning in some areas and certain groups of children may be increasing despite
      the phasing out of lead-containing petrol. Children living in poverty continue to
      be the most vulnerable.

PMID- 24300634
TI  - Chronic diseases are not being managed effectively in either high-risk or low
      risk populations in South Africa.
AB  - BACKGROUND: Primary healthcare is the foundation of a country's healthcare
      system. Without an efficient and cost-effective programme, the level of
      healthcare offered across all levels of health management is adversely affected.
      OBJECTIVE: To analyse the effectiveness of the management of hypertension and
      diabetes mellitus (DM) among two distinct patient populations, one with
      significant cardiovascular risk factors and the other without. METHOD: We
      performed a case control study of a high-risk group of patients presenting with
      chronic critical limb ischaemia (CLI) to the Divisions of Vascular Surgery at
      Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath
      Academic Hospital, and a randomly selected group of 'healthy' community
      participants from Johannesburg's South Western Townships (Soweto). RESULTS: We
      assessed 217 patients with CLI and 1 030 participants from the community. We
      assessed the number of patients who were not achieving their therapeuatic
      targets, among those known to be hypertensive (CLI: 44.7%; community: 59.9%) and
      diabetic (CLI: 83.5%; community: 66%). Undiagnosed diabetes affected 10.8% of
      patients with CLI and 11% of the community sample. CONCLUSION: Traditional
      vascular risk factors are managed poorly at both primary healthcare and at
      tertiary care levels. There is a need to identify factors that will address this
      issue.

PMID- 24300635
TI  - Relationship between environmental exposure to pesticides and anthropometric
      outcomes of boys in the rural Western Cape, South Africa.
AB  - BACKGROUND: Rural residents in the Western Cape (WC), South Africa (SA) are
      highly exposed to agricultural pesticides that could impact their reproductive
      development. However, epidemiological evidence of the effect of pesticides on
      pubertal growth is contradictory. OBJECTIVE: To investigate the effect of
      pesticide exposure measured using indices of environmental exposure to pesticides
      on the pubertal growth of boys in rural WC, SA. METHODS: A cross-sectional study
      of 269 boys (177 of whom gave a history of residing on farms) was conducted. A
      questionnaire was administered, height and weight were measured and body mass
      index was calculated. A proximity index (PI) and spraying index (SI) was
      developed, measuring the lifetime average home distance from pesticide spraying
      and average frequency of spraying pesticides on a farm, respectively. RESULTS:
      Median age of boys was 12.4 years (interquartile range 9.5 - 13.3). More than 60%
      boys had height and weight <50th percentile for age. After adjusting for
      confounders, PI was significantly associated with shorter stature and lower
      weight (-1.7 cm/10-fold decrease, p=0.02 and -1.24 kg/10-fold decrease, p=0.04;
      respectively) and SI was non-significantly associated (-1.4 cm/10-fold increase,
      p=0.05 and -1.1 cm/10-fold increase, p=0.06; respectively). Associations were
      stronger for boys aged <11 years and were weaker when excluding non- farm boys.
      There were no other associations between outcome and exposure. CONCLUSIONS: The
      use of quantitative exposure indices showed that lower heights and weights might
      be associated with pesticide exposure in farm boys v. non-farm boys, but not
      among farm boys. Lower anthropometric measurements among farm boys v. non-farm
      boys appear stronger at a younger age. The indices of environmental exposure to
      pesticides require further development.

PMID- 24300636
TI  - Management of acute fever in children: guideline for community healthcare
      providers and pharmacists.
AB  - Fever is a normal physiological response to illness that facilitates and
      accelerates recovery. Although it is often associated with a self-limiting viral
      infection in children, it may also be a presenting symptom of more serious
      conditions requiring urgent medical care. Therefore, it is essential to
      distinguish between a child with fever who is at high risk of serious illness and
      who requires specific treatment, hospitalisation or specialist care, and those at
      low risk who can be managed conservatively at home. This guideline aims to assist
      pharmacists, primary healthcare workers and general practitioners in risk
      stratifying children who present with fever, deciding on when to refer, the
      appropriate use of antipyretic medication and how to advise parents and
      caregivers.  

PMID- 24300637
TI  - Human genetics in Johannesburg, South Africa: past, present and future.
AB  - Genetic services were set up in Johannesburg, South Africa, in the late 1960s,
      but only became widespread and formalised after the first Professor of Human
      Genetics, Trefor Jenkins, was installed at the University of the Witwatersrand in
      1974. The first services involved chromosome studies, and these developed into
      genetic counselling services. Prenatal diagnosis began to be offered,
      particularly for older women at risk for chromosome abnormalities in the fetus,
      and those at risk for neural tube defects. Genetic screening was then initiated
      for the Jewish community because of their high carrier rate for Tay-Sachs
      disease. Educational courses in human genetics were offered at Wits Medical
      School, and medical as well as other health professionals began to be trained.
      Research, supported by national and international bodies, was integral in the
      activities of the Department (now Division) of Human Genetics and focused on
      genetic conditions affecting the generally understudied black community. In the
      late 1980s the first training programme for genetic counsellors was started at
      MSc level, and postgraduate scientists at MSc and PhD levels studied in and
      qualified through the Department. At the same time molecular genetic laboratories
      were set up. In the late 1990s training for medical geneticists was initiated.
      Extensive high-quality genetic services developed over the four decades were
      comparable to those of most other departments in developed countries.  

PMID- 24300638
TI  - The elusive gene for keratolytic winter erythema.
AB  - Keratolytic winter erythema (KWE), also known as Oudtshoorn skin disease, is
      characterised by a cyclical disruption of normal epidermal keratinisation
      affecting primarily the palmoplantar skin with peeling of the palms and soles,
      which is worse in the winter. It is a rare monogenic, autosomal dominant
      condition of unknown cause. However, due to a founder effect, it occurs at a
      prevalence of 1/7 200 among South African Afrikaans-speakers. In the mid-1980s,
      samples were collected from affected families for a linkage study to pinpoint the
      location of the KWE gene. A genome-wide linkage analysis, using microsatellite
      markers, identified the KWE critical region on chromosome 8p23.1-p22. Subsequent
      genetic studies focused on screening candidate genes in this critical region;
      however, no pathogenic mutations that segregated exclusively with KWE were
      identified. The cathepsin B (CTSB) and farnesyl-diphosphate farnesyltransferase 1
      (FDFT1) genes revealed no potentially pathogenic variants, nor did they show
      differential gene expression in affected skin. Mutation detection in additional
      candidate genes also failed to identify the KWE-associated variant, suggesting
      that the causal variant may be in an uncharacterised functional region.
      Bioinformatic analysis revealed highly conserved regions within the KWE critical
      region and a custom tiling array was designed to cover this region and to search
      for copy number variation. Although the study did not identify a variant that
      segregates exclusively with KWE, it provided valuable insight into the complex
      KWE-linked region. Next-generation sequencing approaches are being used to comb
      the region, but the causal variant for this interesting hyperkeratotic
      palmoplantar phenotype still remains elusive.  

PMID- 24300639
TI  - Thyroid dysfunction in a cohort of South African children with Down syndrome.
AB  - BACKGROUND: While international studies show thyroid dysfunction occurs more
      commonly in individuals with Down syndrome (DS) than in the general population,
      there is a paucity of available data from sub-Saharan Africa. OBJECTIVES: To
      document the range of thyroid function in a cohort of South African children with
      DS, and to assess referral and treatment practices when thyroid dysfunction was
      present. METHODS: A retrospective file-based study of 391 children with DS seen
      at the genetic clinics at three Johannesburg hospitals from 2003 to 2008. Thyroid
      function test (TFT) results (thyroid-stimulating hormone and free thyroxine) and
      demographic details were collected for each child. Endocrine clinic files from
      two of the hospitals were reviewed for additional referral and treatment
      information. RESULTS: The majority (83.6%) of children had at least one TFT, in
      most cases performed between the ages of 2 and 12 months. The most common form of
      thyroid dysfunction was subclinical hypothyroidism (SCH) (28.7%). Up to one-third
      of the patients, including several neonates with abnormal results, were not
      referred for further evaluation and were therefore not receiving the necessary
      treatment. Inter- laboratory biochemical discrepancies and lack of population
      specific reference ranges complicated the interpretation of results. The
      controversy surrounding whether, and how, to treat SCH influenced treatment
      practices. CONCLUSIONS: Thyroid dysfunction is prevalent in South African
      children with DS. There is an urgent need to address the laboratory biochemical
      discrepancies, and to establish guidelines for surveillance and treatment to
      prevent further irreversible neurological and physical impairment.

PMID- 24300640
TI  - Fanconi anaemia in black South African patients heterozygous for the FANCG c.637
      643delTACCGCC founder mutation.
AB  - BACKGROUND: Fanconi anaemia (FA) is an autosomal recessive, genetically
      heterogeneous disorder, characterised by interstrand crosslink-induced chromosome
      breaks, congenital abnormalities and predisposition to malignancies. It has a
      prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in
      the FANCG gene occurs in the homozygous state in 77.5% of southern African
      blacks. OBJECTIVE: To locate additional pathogenic mutations in the FANCG gene of
      black FA patients who were heterozygous for the founder mutation. Methods.
      Further mutation analysis of the FANCG gene was undertaken in 7 patients
      clinically suspected of having FA. The parents of two of the patients were tested
      for the presence of the founder mutation to determine true heterozygosity in the
      patients. To clarify whether or not previously unreported variants were
      pathogenic, 58 random black SA individuals were screened. RESULTS: Three novel
      single base pair deletions, resulting in frameshift mutations (c.247delA,
      c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was
      found to have a single base substitution resulting in a splice site mutation
      (c.1636+1G>A). The remaining three patients were not found to harbour any
      pathogenic mutations. Two non-pathogenic variants were also identified among the
      seven patients. CONCLUSION: The results of this small sample suggest that a
      second common mutation in the FANCG gene is unlikely in this population. However,
      FANCG sequencing should be performed on patients heterozygous for the common
      founder mutation to attempt to confirm their diagnosis.

PMID- 24300641
TI  - Neural tube defects in Gauteng, South Africa: recurrence risks and associated
      factors.
AB  - BACKGROUND: After congenital heart disease, neural tube defects (NTDs) are the
      most common serious structural birth defects in human infants. OBJECTIVES: To (i)
      determine the recurrence risks of NTDs in the population of Gauteng; (ii)
      investigate some of the risk factors shown to be important in the occurrence of
      NTDs in other populations; and (iii) determine their relative importance in the
      aetiology of NTDs in the Gauteng population. METHODS: A retrospective study was
      undertaken of 640 families with a member with an NTD. Data were collected from
      the genetic counselling files held in the Department of Human Genetics for a 28
      year period. RESULTS: A recurrence risk +/- standard deviation (SD) for NTDs of
      2.28+/-0.9% (1/45) was calculated for the population. There was no significant
      difference between the risk of recurrence 0.73+/-1.0% for the black families
      (n=98) compared with those for the total sample (N=621). The risk rose to 4.16%
      after giving birth to two affected children. Analysis of the gender of those with
      NTDs showed that significantly more female infants (male:female ratio 0.82) were
      affected. The study also showed that while maternal age was not a significant
      risk factor for the occurrence of NTDs, maternal parity did play a role, and
      first and last children were at increased risk. In addition, a higher occurrence
      of spontaneous abortions and of apparently unrelated congenital malformations in
      other offspring was found in families with a child with an NTD. CONCLUSIONS: This
      study provides unique information relevant to the genetic counselling of families
      with a member with an NTD in our population. All affected families should be
      referred to a genetics service for appropriate counselling.

PMID- 24300642
TI  - Haematological implications of folate food fortification.
AB  - Reports from some Western countries indicate that mandatory folate food
      fortification (FFF) has substantially reduced the prevalence of folate
      deficiency, leading to calls for folate testing following FFF to be limited to
      specific indications such as macrocytic anaemia. This is premature for low-income
      countries, where folate deficiency is predominantly the result of poor intake
      coupled with the increasing demand in pregnancy. There is also evidence that HIV
      infection is prejudicial to folate nutrition, and low-income HIV-infected women
      and their offspring could be among the most susceptible to folate deficiency. In
      assessing folate nutrition, the value of serum folate has been compromised by
      FFF, and both serum and red cell folate are necessary for optimal assessment of
      folate status. Although the limited data available suggest that large-scale
      masking of vitamin B12 deficiency by FFF has not occurred, it has been suggested
      that B12 be incorporated into folate-fortified foods. However, significant B12
      deficiency is usually due to malabsorption, and physiological doses added to food
      would be of questionable value because they would not be absorbed. Extensive
      work, especially randomised clinical trials, must be done before dietary
      intervention with B12 on a national scale can be justified.  

PMID- 24300643
TI  - The molecular basis of mutagenesis - 40 years of research on genomic integrity.
AB  - This article reviews the multiple mechanisms by which both prokaryotes and
      eukaryotes remove or tolerate various types of naturally occurring and
      exogenously generated base damage in DNA.  

PMID- 24300644
TI  - Biology and genetics of oculocutaneous albinism and vitiligo - common
      pigmentation disorders in southern Africa.
AB  - Pigmentation disorders span the genetic spectrum from single-gene autosomal
      recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant
      disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA
      connotes a group of disorders that result in hypopigmented skin due to decreased
      melanin production in melanocytes and loss of visual acuity. There are four non
      syndromic forms, OCA1-4, which are classified based on the gene that is mutated
      (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively).
      Despite the fact that multiple genes account for the various forms of OCA, the
      phenotypes of all four forms result from disruption in the maturation and
      trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal
      recessive disorder among southern African blacks, affecting 1/3 900 individuals;
      while OCA3, although rare, is most prevalent in southern Africa. Another common
      pigmentation disorder in southern Africa is vitiligo, which affects 1 - 2% of
      people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes
      are destroyed due to an autoimmune response. The aetiology underlying this
      disorder is poorly understood, although recent genetic association studies have
      begun to shed light on the contributing factors. Pigmentation disorders have
      significant psychosocial implications and co-morbidities, yet therapies are still
      lacking. Recent progress in our understanding of the pathobiology of both
      albinism and vitiligo may herald novel treatment strategies for these disorders. 

PMID- 24300645
TI  - Testing for haemoglobinopathies in Johannesburg, South Africa: a 30-year review.
AB  - BACKGROUND: Haemoglobinopathies are seen mostly in regions where malaria occurs
      or has occurred, but population migration has resulted in affected individuals
      being identified in many countries globally. The first molecular genetics
      services for diagnostic testing and prenatal diagnosis were established, both
      worldwide and in South Africa (SA), for haemoglobinopathies. OBJECTIVE: To
      analyse the diagnostic service offered by the Division of Human Genetics,
      National Health Laboratory Service and University of the Witwatersrand, from 1983
      to 2012. METHODS: A retrospective file analysis (N=1 249) was performed for all
      individuals who had molecular genetic testing for alpha-thalassaemia, beta
      thalassaemia and sickle cell anaemia to examine indications for testing,
      population origins of patients and molecular genetics findings. RESULTS: The
      alpha-thalassaemia testing was requested predominantly to explain microcytic
      hypochromic haematological indices. Five alpha-globin deletions were identified,
      the most common being the -alpha3.7, in individuals of different ethnicities. For
      beta-thalassaemia and sickle cell anaemia, most testing was performed for
      prenatal diagnosis purposes. For sickle cell anaemia, most prenatal tests were
      requested by African families. The beta-thalassaemia families were mostly of
      Indian or Mediterranean origin. The most common mutation identified in all Indian
      groups was IVS1 nt5 (G>C) (c.92+5G>C) and in individuals from the Mediterranean,
      IVS1 nt110 (G>A) (c.93-21G>A). CONCLUSION: The molecular genetics service for
      haemoglobinopathies in SA is comprehensive and specific to the needs of local
      ethnic groups. Clinically significant haemoglobinopathies occur at significant
      frequencies in specific high-risk ethnic groups. Appropriate screening programmes
      should be initiated so that genetic counselling and reproductive options can be
      offered.

PMID- 24300646
TI  - Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other
      FMR-1-related disorders in Johannesburg, South Africa: a 20-year review.
AB  - BACKGROUND: Fragile X syndrome (FXS), the most common inherited cause of
      intellectual disability (ID) worldwide, is caused by the expansion of a CGG
      repeat in the fragile X mental retardation gene (FMR-1) gene. OBJECTIVES; To
      review, retrospectively, the genetic services for FXS and other FMR-1-related
      disorders - including fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR
      1-related primary ovarian insufficiency (POI) - at the Division of Human
      Genetics, Johannesburg, for diagnostic, carrier and prenatal genetic
      testing.Methods. The records of 2 690 patients with ID and suspected FXS
      (ID/?FXS) who had genetic testing for FMR-1 between 1992 and 2012 were reviewed.
      Of these, 2 239 had diagnostic testing, 430 carrier or cascade testing and 17
      prenatal testing for FXS. Four had FXTAS or POI testing. Polymerase chain
      reaction (PCR) and/or Southern blotting techniques were used to test the
      patients' samples for FMR-1 and FMR-2 expansions. RESULTS; Of the 2 239 patients
      who had diagnostic testing, 128 (5.7%) had a full mutation, 12 (0.5%) had a
      premutation and 43 (1.9%) an intermediate allele. In 17 prenatal tests, eight
      fetuses tested positive for FXS. FMR-1 CGG repeat distribution analysis in 1 532
      males negative for the FMR-1 expansion showed that 29 and 30 CGG repeats were the
      most common (61.1%), but distribution was significantly different in the black
      and white populations.CONCLUSION; The findings support the presence of FXS, as
      the most common cause of ID, in all local populations. The FMR-1 CGG repeat
      distribution varied from that found in other studies. The number of family
      members tested was relatively low suggesting that many at-risk individuals are
      not being referred.

PMID- 24300647
TI  - Genetic testing for Duchenne/Becker muscular dystrophy in Johannesburg, South
      Africa.
AB  - BACKGROUND: Genetic testing for Duchenne/Becker muscular dystrophy (DMD/BMD)
      mutations initially involved multiplex polymerase chain reaction (mPCR), which
      targeted two mutation hotspots in the gene and detected deletions in affected
      males. A newer technology, multiplex ligation-dependent probe amplification
      (MLPA), was introduced for diagnostic testing in 2007. OBJECTIVES: To evaluate
      MLPA relative to mPCR as a technique for DMD/BMD diagnostic testing and to
      establish whether the mutation profile in affected individuals differs between
      different South African ethnic groups. METHODS; From January 2000 - May 2007,
      genetic diagnostic testing for DMD/BMD was undertaken in 128 male patients using
      mPCR. From May 2007 onwards, MLPA replaced this technique and 261 males were
      investigated. MLPA is a kit-based technology available from MRC-Holland.Results.
      Of the 128 and 261 probands tested using mPCR and MLPA, respectively, 31% and 34%
      were found to carry a deletion mutation. Further, MLPA could detect duplication
      mutations (11.5%), complex rearrangements (1.5%) and small mutations (1.5%). In
      black patients, deletion mutations were found to cluster in the 3' region of the
      gene. No population-specific pathogenic mutations were found. CONCLUSIONS: The
      mutation detection rate for mPCR and MLPA is similar for deletion mutations, but
      MLPA proved to be a better diagnostic approach as it could detect other types of
      mutations as well, including duplications, complex rearrangements and small
      mutations. MLPA could also diagnose mutation status in at-risk female relatives,
      which is not possible with mPCR.

PMID- 24300648
TI  - STR null alleles complicate parentage testing in South Africa.
AB  - BACKGROUND: Null alleles complicate parentage testing because they do not
      contribute positively to phenotypes.Objectives. To survey South African
      populations for null alleles at short tandem repeat (STR) loci used in parentage
      testing. METHODS: Paternity case data were scanned for apparent contradictions
      compared with Mendelian inheritance that could be due to null alleles. Estimates
      of null allele frequencies were obtained from tallies of apparent carriers.
      RESULTS: Three of 15 loci appeared to have null alleles at appreciable
      frequencies and five showed no evidence of null alleles. A null allele at the vWA
      locus reached a frequency of ~0.3% in the black population and approximately
      three times this frequency in the coloured population. No apparent vWA null
      carriers were detected in whites suggesting that the Khoisan were the major
      contributors of the null alleles to coloureds. The apparent genotypes of a sample
      of TPOX null carriers changed from homozygous to heterozygous when they were
      retyped using different polymerase chain reaction primers. The revealed allele
      was allele 6 in every case. A D13S317 null allele was detected at relatively low
      frequencies in the black and coloured samples but 2/145 Indian (Asian) parents
      appear to be carriers, suggesting that it could be common in Indians. CONCLUSION:
      Three of the 15 forensically relevant STR loci investigated had null alleles at
      significant frequencies in South African populations. Failure to allow for the
      presence of null alleles can have a large impact on the outcome of parentage
      tests.

PMID- 24300649
TI  - Lemba origins revisited: tracing the ancestry of Y chromosomes in South African
      and Zimbabwean Lemba.
AB  - BACKGROUND: Previous historical, anthropological and genetic data provided
      overwhelming support for the Semitic origins of the Lemba, a Bantu-speaking
      people in southern Africa. OBJECTIVE: To revisit the question concerning genetic
      affinities between the Lemba and Jews. METHODS: Y-chromosome variation was
      examined in two Lemba groups: one from South Africa (SA) and, for the first time,
      a group from Zimbabwe (Remba), to re-evaluate the previously reported Jewish
      link. RESULTS: A sample of 261 males (76 Lemba, 54 Remba, 43 Venda and 88 SA
      Jews) was initially analysed for 16 bi-allelic and 6 short tandem repeats (STRs)
      that resulted in the resolution of 102 STR haplotypes distributed across 13
      haplogroups. The non-African component in the Lemba and Remba was estimated to be
      73.7% and 79.6%, respectively. In addition, a subset of 91 individuals (35 Lemba,
      24 Remba, 32 SA Jews) with haplogroup J were resolved further using 6 additional
      bi-allelic markers and 12 STRs to screen for the extended Cohen modal haplotype
      (CMH). Although 24 individuals (10 Lemba and 14 SA Jews) were identified as
      having the original CMH (six STRs), only one SA Jew harboured the extended
      CMH.CONCLUSIONS. While it was not possible to trace unequivocally the origins of
      the non-African Y chromosomes in the Lemba and Remba, this study does not support
      the earlier claims of their Jewish genetic heritage.

PMID- 24300650
TI  - Attaining human dignity for people with birth defects: a historical perspective.
AB  - People with birth defects have been stigmatised, marginalised and discriminated
      against for millennia, diminishing their human dignity and abrogating their human
      rights. Beginning with the United Nations Universal Declaration of Human Rights,
      promulgated in 1947, the circumstances in which human dignity in healthcare for
      people with birth defects could be achieved arose, and this was accomplished over
      the next 65 years through the insight, hard work and dedication of a select group
      of people and organisations. In 2010 the World Health Organization prioritised
      services for the care and prevention of birth defects, particularly in middle-
      and low-income countries. Translating what has been achieved into human rights in
      healthcare for people with birth defects is the next objective.  

PMID- 24300651
TI  - The role of patient advocacy/parent support groups.
AB  - Parent support/patient advocacy groups for rare genetic disorders have emerged as
      an important force. They provide information, encourage research (both by
      participation in research and by raising money for research), give families and
      affected family members the opportunity to learn from each other, and open the
      way for social and intellectual interaction between families, affected
      individuals, researchers and healthcare providers. New IT technologies increase
      the opportunities for collaboration and information exchange around the world.
      These groups have become an important resource for families, genetic counsellors
      and medical/clinical genetic professionals.  

PMID- 24300652
TI  - Ethical issues and Huntington's disease.
AB  - The practice of genetic counselling gives rise to many ethical dilemmas, and
      counsellors need to be familiar with the principles of biomedical ethics. The
      primary principles include respect for autonomy, beneficence, non-maleficence and
      justice. A case of identical twins at 50% risk for Huntington's disease, in which
      only one twin sought predictive testing for this dominantly inherited disease,
      created several ethical dilemmas. Another case where predictive testing was
      carried out on two young children, at high risk, by a laboratory at the request
      of an adoption agency and a doctor, with a view to giving information to the
      foster parents, also posed many ethical conundrums for the counsellor. The
      ethical issues that arose in these cases are discussed in this paper.  

PMID- 24300653
TI  - The influence of HIV status on prenatal genetic diagnosis choices.
AB  - BACKGROUND: At-risk women of advanced maternal age (AMA) can choose to have
      second-trimester invasive testing for a prenatal genetic diagnosis on the fetus.
      Being HIV-positive can complicate the decision-making process. OBJECTIVE: To
      document HIV status and prenatal genetic diagnosis choices in women of AMA
      attending genetic clinics in Johannesburg, South Africa, for counselling on the
      risks of abnormalities in their fetuses. METHODS: Data on the characteristics of
      the sample, HIV status and prenatal diagnosis decisions were collected
      retrospectively from the files of 350 women (>34 years) counselled for AMA in
      genetic clinics in Johannesburg and Pretoria. The time period was 6 months in
      2003 and 6 months in 2004. A sample of the women (n=15) who were HIV-positive
      were interviewed and completed questionnaires on their understanding of their
      situation. The data were analysed and submitted to statistical testing. RESULTS:
      Of the 350 women, 183 (52.3%) were HIV-negative, 44 (12.6%) HIV-positive, and 123
      (35.1%) of unknown status. Significantly more HIV-negative patients (79/183,
      43.2%) than those who were HIV-positive (6/44, 13.6%) had amniocentesis performed
      for fetal diagnosis. Most of the interviewed women (12/15, 80.0%) understood the
      severity of HIV infection, 5 (33.3%) considered termination of pregnancy based on
      the transmission risk, and 4 (26.7%) would have requested amniocentesis and
      prenatal diagnosis if they had been HIV-negative. CONCLUSION. Decision-making
      regarding prenatal genetic diagnosis is influenced by HIV status among older
      women. Effective access to highly active antiretroviral therapy throughout
      pregnancy would make decision-making easier for these women.

PMID- 24300654
TI  - Eating the dead in Madagascar.
AB  - Cannibalism has been poorly understood and has seldom been studied, since it was
      often suppressed by missionaries and colonial administrators, and very few
      societies still practise it. Cannibalistic practices are more complex than was
      originally thought. They may be supported in societies under stress or in times
      of famine, to reflect aggression and antisocial behaviour (in cases where the
      bodies of enemies killed in battle or people who have harmed the family are
      eaten), or to honour a dead kinsman. It was, for example, noted in Madagascar
      during the imperial campaigns of Ranavalona I in the period 1829 - 1853. Two
      types of cannibalism have been described: exocannibalism, where enemies were
      consumed, and endocannibalism, where dead relatives were eaten to assist their
      passing to the world of the ancestors, or to prolong contact with beloved and
      admired family members and absorb their good qualities. This article reviews some
      of the beliefs and motivations that surrounded the cannibalistic practices of the
      people of Madagascar in the 19th century.  

PMID- 24300655
TI  - Paediatric spirometry guideline of the South African Thoracic Society: Part 1.
AB  - Spirometry forms an important component in the diagnosis and management of
      pulmonary diseases in children. In the paediatric setting, there are different
      challenges in terms of performance and interpretation of good quality and
      reliable tests. An awareness of the physiological and developmental aspects that
      exist in children is necessary to improve the quality and reliability of
      spirometry. We reviewed the recommendations on the technical aspects of
      performing spirometry in children, from the available guidelines and clinical
      trials. The focus was on the indications, methods and the interpretation of lung
      function tests in children <12 years of age. Reliable lung function testing can
      be performed in children, but an awareness of the limitations, the use of
      incentives and a dedicated lung function technologist are necessary.  

PMID- 24300656
TI  - Are community service doctors equipped to address priority health needs in South
      Africa?

PMID- 24300657
TI  - Fever in children - what it means and what to do.

PMID- 24300658
TI  - Professor Trefor Jenkins: a tribute.

PMID- 24300659
TI  - Predicting outcome in a postacute stroke rehabilitation programme.
AB  - This study aims to evaluate and predict outcome as part of routine quality
      assessment of an inpatient stroke rehabilitation programme. By relating
      functional outcome to patient characteristics, including variables from the
      quality of life domain, we aim to find a set of variables that can be useful for
      prognosis, stratification and programme improvement. Data were collected, before
      and after rehabilitation, from a prospective quality registration database.
      Included were 250 patients in inpatient stroke rehabilitation after sustaining a
      first or recurrent ischemic or haemorrhagic stroke. Functional status was
      measured with the Barthel Index and the Academic Medical Centre Linear Disability
      Score. Health-related quality of life (HrQoL) was measured with the COOP/WONCA
      and the Nottingham Health Profile. Significant improvements were found on all
      outcome measures. A lower functional admission score, older age, more severe
      stroke, more pain and more negative emotional reactions on admission were found
      to be independent predictors of a lower outcome score, explaining 39.5% of its
      variance. Subjective (HrQoL) factors such as negative emotion and pain have an
      adverse effect on outcome of stroke rehabilitation, in addition to stroke
      severity, age and functional status at admission. These factors need to be taken
      into account in screening, clinical decision making and treatment design. 

PMID- 24300660
TI  - The special status of verbal knowledge in semantic memory: evidence from
      performance of semantically impaired subjects on verbalizable and non
      verbalizable versions of the object decision task.
AB  - According to the semantic hub hypothesis, a supramodal semantic hub is equally
      needed to deal with verbal and extraverbal "surface" representations. Damage to
      the supramodal hub is thought to underlie the crossmodal impairment observed in
      selective semantic deficits. In the present paper, we provide evidence supporting
      an alternative view: we hold that semantic impairment is not equal across domains
      but affects verbal behavior disproportionately. We investigated our hypothesis by
      manipulating the verbal load in an object decision task. Two pathological groups
      showing different levels of semantic impairment were enrolled together with their
      normal controls. The severe group included 10 subjects with semantic dementia and
      the mild group 10 subjects with Alzheimer's disease. In keeping with our
      hypothesis, when shifting from the low verbal load to the high verbal load
      condition, brain-damaged individuals, as compared to controls, showed a
      disproportionate impairment as a function of the severity of their semantic
      deficit. 

PMID- 24300661
TI  - Nanofabrication of gate-defined GaAs/AlGaAs lateral quantum dots.
AB  - A quantum computer is a computer composed of quantum bits (qubits) that takes
      advantage of quantum effects, such as superposition of states and entanglement,
      to solve certain problems exponentially faster than with the best known
      algorithms on a classical computer. Gate-defined lateral quantum dots on
      GaAs/AlGaAs are one of many avenues explored for the implementation of a qubit.
      When properly fabricated, such a device is able to trap a small number of
      electrons in a certain region of space. The spin states of these electrons can
      then be used to implement the logical 0 and 1 of the quantum bit. Given the
      nanometer scale of these quantum dots, cleanroom facilities offering specialized
      equipment- such as scanning electron microscopes and e-beam evaporators- are
      required for their fabrication. Great care must be taken throughout the
      fabrication process to maintain cleanliness of the sample surface and to avoid
      damaging the fragile gates of the structure. This paper presents the detailed
      fabrication protocol of gate-defined lateral quantum dots from the wafer to a
      working device. Characterization methods and representative results are also
      briefly discussed. Although this paper concentrates on double quantum dots, the
      fabrication process remains the same for single or triple dots or even arrays of
      quantum dots. Moreover, the protocol can be adapted to fabricate lateral quantum
      dots on other substrates, such as Si/SiGe. 

PMID- 24300662
TI  - Does 5HTTLPR long allele prevent hospitalization? Test of Hardy-Weinberg
      equilibrium.
AB  - Many studies suggest an association of the serotonin transporter gene
      polymorphism (5HTTLPR) long allele with better antidepressant treatment response
      than the short allele. However, there is controversy over these findings. We
      hypothesized that if the long allele is associated with a better outcome, we
      would find fewer inpatients with the long allele compared with the short allele.
      Chart review identified 925 depressed inpatients and 201 outpatients genotyped
      for 5HTTLPR. The sample was primarily White (>90%). We tested potential
      departures from Hardy-Weinberg equilibrium for each sample. We analyzed three
      independent sets of inpatient samples separately and combined, a White subgroup
      of 791 patients of the total 925 inpatients, and 201 outpatients. There was no
      departure from Hardy-Weinberg equilibrium with any of these samples. We also
      compared 5HTTLPR genotype prevalence between 925 inpatients and 201 outpatients,
      which showed no statistically significant difference. 

PMID- 24300664
TI  - DF's visual brain in action: the role of tactile cues.
AB  - Patient DF, an extensively-tested woman with visual form agnosia from ventral
      stream damage, is able to scale her grip aperture to match a goal object's
      geometry when reaching out to pick it up, despite being unable to explicitly
      distinguish amongst objects on the basis of their different geometries. Using
      evidence from a range of sources, including functional MRI, we have proposed that
      she does this through a functionally intact visuomotor system housed within the
      dorsal stream of the posterior parietal lobe. More recently, however, Schenk
      (2012a). The Journal of Neuroscience, 32(6), 2013-2017; Schenk (2012b). Trends in
      Cognitive Sciences, 16(5), 258-259. has argued that DF performs well in visually
      guided grasping, not through spared and functioning visuomotor networks in the
      dorsal stream, but because haptic feedback about the locations of the edges of
      the target is available to calibrate her grasps in such tasks, whereas it is not
      available in standard visual perceptual tasks. We have tested this 'calibration
      hypothesis' directly, by presenting DF with a grasping task in which the visible
      width of a target varied from trial to trial while its actual width remained the
      same. According to the calibration hypothesis, because haptic feedback was
      completely uninformative, DF should be unable to calibrate her grip aperture in
      this task. Contrary to this prediction, we found that DF continued to scale her
      grip aperture to the visual width of the targets and did so well within the range
      of healthy controls. We also found that DF's inability to distinguish shapes
      perceptually is not improved by providing haptic feedback. These findings
      strengthen the notion that DF's spared visuomotor abilities are driven largely by
      visual feedforward processing of the geometric properties of the target.
      Crucially, these findings also indicate that simple tactile contact with an
      object is needed for the visuomotor dorsal stream to be engaged, and accordingly
      enables DF to execute visually guided grasping successfully. This need for
      actions to have a tangible endpoint provides an important new modification of the
      Two Visual Systems theory. 

PMID- 24300663
TI  - Association of the catechol-O-methyltransferase val158met polymorphism and
      anxiety-related traits: a meta-analysis.
AB  - OBJECTIVES: The aims of this study were (i) to examine genotypic association of
      the catechol-O-methyltransferase (COMT) val158met polymorphism with anxiety
      related traits with a meta-analysis; (ii) to examine sex and ethnicity as
      moderators of the association; and (iii) to evaluate whether the association
      differed by particular anxiety traits. METHODS: Association studies of the COMT
      val158met polymorphism and anxiety traits were identified from the PubMed or
      PsycInfo databases, conference abstracts, and listserv postings. Exclusion
      criteria were (a) pediatric samples, (b) exclusively clinical samples, and (c)
      samples selected for a nonanxiety phenotype. Standardized mean differences in
      anxiety between genotypes were aggregated to produce mean effect sizes across all
      available samples, and for subgroups stratified by sex and ethnicity (Whites vs.
      Asians). Construct-specific analysis was conducted to evaluate the association of
      COMT with neuroticism, harm avoidance, and behavioral inhibition. RESULTS: Twenty
      seven eligible studies (N=15 979) with available data were identified. Overall
      findings indicate sex-specific and ethnic-specific effects: valine homozygotes
      had higher neuroticism than methionine homozygotes in studies of White males
      [mean effect size(Equation is included in full-text article.)=0.13; 95% CI 0.02,
      0.25; P=0.03], and higher harm avoidance in studies of Asian males ((Equation is
      included in full-text article.)=0.43; 95% CI 0.14, 0.72; P=0.004). No significant
      associations were found in women and effect sizes were diminished when studies
      were aggregated across ethnicity or anxiety traits. CONCLUSION: This meta
      analysis provides evidence for sex and ethnic differences in the association of
      the COMT val158met polymorphism with anxiety traits. Our findings contribute to
      current knowledge on the relation between prefrontal dopaminergic transmission
      and anxiety.

PMID- 24300667
TI  - Photo-bleaching of Chlamydomonas reinhardtii after dark-anoxic incubation.
AB  - In aerobes, anoxia impairs mitochondrial energy generation as well as
      biosynthesis and degradation of essential cell components. In a recent analysis
      we have shown that the unicellular green alga Chlamydomonas reinhardtii responds
      to anaerobiosis in the dark by significant changes of the transcriptome, which,
      in summary, were directed at saving and economizing energy. Several of the
      transcriptional changes were related to photosynthesis and were accompanied by
      reduced amounts of chlorophylls and plastid lipids as well as lowered photosystem
      2 quantum yields. A further noticeable pattern was a transcriptional upregulation
      of various genes encoding O 2 dependent enzymes of central biosynthetic pathways.
      However, cells do not divide in dark-anoxia, indicating that C. reinhardtii
      cannot compensate for the lack of O 2 and light. Upon return to aeration and
      light, cultures show severe photo-bleaching, which might be a stress reaction,
      but also part of an acclimation process or its disturbance. 

PMID- 24300666
TI  - Inducing autophagy: a comparative phosphoproteomic study of the cellular response
      to ammonia and rapamycin.
AB  - Autophagy is a lysosomal-mediated catabolic process, which through degradation of
      different cytoplasmic components aids in maintaining cellular homeostasis and
      survival during exposure to extra- or intracellular stresses. Ammonia is a
      potential toxic and stress-inducing byproduct of glutamine catabolism, which has
      recently been found to induce autophagy in an MTOR independent way and support
      cancer cell survival. In this study, quantitative phosphoproteomics was applied
      to investigate the initial signaling events linking ammonia to the induction of
      autophagy. The MTOR inhibitor rapamycin was used as a reference treatment to
      emphasize the differences between an MTOR-dependent and -independent autophagy
      induction. By this means 5901 phosphosites were identified of which 626 were
      treatment-specific regulated and 175 were coregulated. Investigation of the
      ammonia-specific regulated sites supported that MTOR activity was not affected,
      but indicated increased MAPK3 activity, regulation of proteins involved in Rho
      signal transduction, and a novel phosphorylation motif, serine-proline-threonine
      (SPT), which could be linked to cytoskeleton-associated proteins. MAPK3 could not
      be identified as the primary driver of ammonia-induced autophagy but instead the
      data suggested an upregulation of AMPK and the unfolded protein response (UPR),
      which might link ammonia to autophagy induction. Support of UPR induction was
      further obtained from the finding of increased protein levels of the ER stress
      markers DDIT3/CHOP and HSPA5 during ammonia treatment. The large-scale data set
      presented here comprises extensive high-quality quantitative information on
      phosphoprotein regulation in response to 2 very different autophagy inducers and
      should therefore be considered a general resource for the community. 

PMID- 24300668
TI  - Procedures for identifying infectious prions after passage through the digestive
      system of an avian species.
AB  - Infectious prion (PrP(Res)) material is likely the cause of fatal,
      neurodegenerative transmissible spongiform encephalopathy (TSE) diseases(1).
      Transmission of TSE diseases, such as chronic wasting disease (CWD), is presumed
      to be from animal to animal(2,3) as well as from environmental sources(4-6).
      Scavengers and carnivores have potential to translocate PrP(Res) material through
      consumption and excretion of CWD-contaminated carrion. Recent work has documented
      passage of PrP(Res) material through the digestive system of American crows
      (Corvus brachyrhynchos), a common North American scavenger(7). We describe
      procedures used to document passage of PrP(Res) material through American crows.
      Crows were gavaged with RML-strain mouse-adapted scrapie and their feces were
      collected 4 hr post gavage. Crow feces were then pooled and injected
      intraperitoneally into C57BL/6 mice. Mice were monitored daily until they
      expressed clinical signs of mouse scrapie and were thereafter euthanized.
      Asymptomatic mice were monitored until 365 days post inoculation. Western blot
      analysis was conducted to confirm disease status. Results revealed that prions
      remain infectious after traveling through the digestive system of crows and are
      present in the feces, causing disease in test mice. 

PMID- 24300670
TI  - Defining quality in surgical training: perceptions of the profession.
AB  - BACKGROUND: To improve surgical training standards, it is necessary to first
      define the elements of high-quality training and methods for measuring them.
      METHODS: Semistructured interviews were conducted with attending (n = 10) and
      resident (n = 10) general surgeons. An interview topic guide was used to elicit
      end users' opinions on indicators of training quality and methods to measure
      them. Interviews were recorded, transcribed verbatim, and coded using a framework
      to identify emergent themes. Sampling ceased once thematic saturation was
      achieved. RESULTS: Key surgical training quality indicators include continuity
      (80% of participants) and relationship (95%) between trainee and trainer, level
      of supervision (85%), and an optimal volume (95%) and mix (90%) of operative
      cases. All surgeons felt that trainee logbook analysis and feedback was
      essential. The majority (85%) felt that training analysis should be freely
      available to create accountability for hospitals and attending surgeons (70%) and
      encourage competition (70%) to drive up standards. Only 30% felt that all
      attending surgeons should offer training. CONCLUSIONS: Surgical training quality
      needs to be robustly assessed. Transparency in training outcomes will create
      competition and raise standards of surgical education.

PMID- 24300669
TI  - Recent progress in adjuvant discovery for peptide-based subunit vaccines.
AB  - Peptide-based subunit vaccines are of great interest in modern immunotherapy as
      they are safe, easy to produce and well defined. However, peptide antigens
      produce a relatively weak immune response, and thus require the use of
      immunostimulants (adjuvants) for optimal efficacy. Developing a safe and
      effective adjuvant remains a challenge for peptide-based vaccine design. Recent
      advances in immunology have allowed researchers to have a better understanding of
      the immunological implication of related diseases, which facilitates more
      rational design of adjuvant systems. Understanding the molecular structure of the
      adjuvants allows the establishment of their structure-activity relationships
      which is useful for the development of next-generation adjuvants. This review
      summarizes the current state of adjuvants development in the field of synthetic
      peptide-based vaccines. The structural, chemical and biological properties of
      adjuvants associated with their immunomodulatory effects are discussed. 

PMID- 24300671
TI  - Unique risks for mortality in patients with end-stage renal disease undergoing
      nonemergent colorectal surgery.
AB  - BACKGROUND: The aim of this study was to identify unique risk factors for
      mortality in patients with end-stage renal disease undergoing nonemergent
      colorectal surgery. METHODS: A multivariate logistic regression model predicting
      30-day mortality was constructed for patients with end-stage renal disease
      undergoing nonemergent colorectal procedures. Data were obtained from the
      National Surgical Quality Improvement Program (2005-2010). RESULTS: Among the 394
      patients analyzed, those with serum creatinine levels >7.5 mg/dL had .07 times
      the adjusted mortality risk of those with levels <3.5 mg/dL. For colorectal
      surgery patients, the average serum creatinine level was 5.52 +/- 2.6 mg/dL, and
      mortality was 13% (n = 50). CONCLUSIONS: High serum creatinine was associated
      with a lower risk for mortality in patients with end-stage renal disease, even
      though creatinine is often considered a risk factor for surgery. These results
      show how variables from a patient-centered subpopulation can differ in meaning
      from the general population.

PMID- 24300673
TI  - The dilemma of treating major burns in South Africa.
AB  - The major challenge facing South African burn surgeons is the current and future
      management of major burns. Survival is greatly dependent on adequate therapeutic
      measures. Various therapeutic measures can be instituted to overcome the shortage
      of donor skin, as we describe. Each of these methods has its specific role in the
      management of major burns. The use of very expensive and highly specialised
      techniques for individual patients cannot be justified when more accessible and
      cost-effective methods are available. To serve the greater population of burn
      victims, every effort should be made to use these available methods rather than
      channelling scarce financial resources into procedures that have a very limited
      role in South Africa.  

PMID- 24300674
TI  - External patient temperature control in emergency centres, trauma centres,
      intensive care units and operating theatres: a multi-society literature review.
AB  - Here we review the available literature supporting the routine and timely use of
      external patient warming devices of all possible types during emergency
      department and peri-operative situations, including the role of best ambient
      temperature, and provides a best-practice statement on the need for such devices.
      It aims to present a guideline document endorsed by the major South African
      professional societies in the field of emergency and peri-operative care. 

PMID- 24300675
TI  - Traumatic brain injury: the South African landscape.

PMID- 24300672
TI  - West Nile virus drug discovery.
AB  - The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued
      spread throughout the Americas, parts of Europe, the Middle East and Africa,
      underscored the need for WNV antiviral development. Here, we review the current
      status of WNV drug discovery. A number of approaches have been used to search for
      inhibitors of WNV, including viral infection-based screening, enzyme-based
      screening, structure-based virtual screening, structure-based rationale design,
      and antibody-based therapy. These efforts have yielded inhibitors of viral or
      cellular factors that are critical for viral replication. For small molecule
      inhibitors, no promising preclinical candidate has been developed; most of the
      inhibitors could not even be advanced to the stage of hit-to-lead optimization
      due to their poor drug-like properties. However, several inhibitors developed for
      related members of the family Flaviviridae, such as dengue virus and hepatitis C
      virus, exhibited cross-inhibition of WNV, suggesting the possibility to re
      purpose these antivirals for WNV treatment. Most promisingly, therapeutic
      antibodies have shown excellent efficacy in mouse model; one of such antibodies
      has been advanced into clinical trial. The knowledge accumulated during the past
      fifteen years has provided better rationale for the ongoing WNV and other
      flavivirus antiviral development. 

PMID- 24300676
TI  - The promotion of road safety by healthcare professionals in South Africa.

PMID- 24300677
TI  - Demographic profile of severe traumatic brain injury admissions to Red Cross War
      Memorial Children's Hospital, 2006 - 2011.
AB  - BACKGROUND: Paediatric traumatic brain injury (PTBI) is a major public health
      problem. However, recent epidemiological data for PTBI in South Africa (SA) are
      lacking. OBJECTIVES: To establish a demographic profile of severe PTBI admissions
      to the Red Cross War Memorial Children's Hospital (RCWMCH) over a 5-year period,
      by investigating trends in annual admissions, age, sex, language, time and day of
      injury, and aetiology. Methods. This retrospective, descriptive, quantitative
      study included children admitted to the RCWMCH with severe traumatic brain injury
      (TBI) between June 2006 and April 2011, who required intracranial monitoring. We
      used the Division of Paediatric Neurosurgery's TBI database to identify cases for
      inclusion in the study and to gather demographic and injury information. RESULTS:
      Descriptive statistics suggested that: (i) the number of annual admissions did
      not vary substantially across the study period; (ii) the peak admission age was 6
      years; (iii) more boys than girls were admitted; (iv) the major mechanism of
      injury was pedestrian road traffic accidents; and (v) most injuries occurred on
      weekends. These results are discussed against the backdrop of international
      research on PTBI and reflect the extent to which epidemiological findings on TBI
      in high-income countries compare with those from low- and middle-income countries
      such as SA. CONCLUSION: The identification of aetiological factors and the
      description of demographic profiles of children sustaining TBI constitutes a
      basis for preventative policy administration and intervention strategies in SA.

PMID- 24300678
TI  - The effect of traffic calming on pedestrian injuries and motor vehicle collisions
      in two areas of the eThekwini Municipality: a before-and-after study.
AB  - BACKGROUND: Motor vehicle collisions and pedestrian injuries in areas where
      schools are located are public health problems in Durban. OBJECTIVE: To evaluate
      the effect of traffic calming humps on the number and severity of incidences of
      collisions and injuries in the Chatsworth and KwaMashu residential areas of the
      eThekwini Municipality. METHODS: The evaluation used an observational interrupted
      time-series study design, with data obtained from the eThekwini Traffic Authority
      for roads constituting the routes to 34 schools for 2 years prior to and
      following the implementation of road humps (excluding the intervening year of
      implementation). A non-probability convenience sample of 19 schools with 39 roads
      in Chatsworth and 15 schools with 24 roads in KwaMashu was selected. RESULTS: The
      traffic calming humps improved safety in both areas with respect to the severity
      of collisions. Serious pedestrian-vehicle collisions (PVCs) dropped by 23% and
      22%, while fatal collisions decreased by 68% and 50% in Chatsworth and KwaMashu,
      respectively. The median annual PVC rate/km of road/year decreased from 1.41 to
      0.96 (p=0.007) and from 2.35 to 1.40 (p<0.001) in Chatsworth and KwaMashu,
      respectively. There was a 1.6% reduction in the median number of fatal or serious
      PVCs after implementation in Chatsworth (p=0.03) while in KwaMashu, although the
      number of collisions decreased, the median number increased by 9% (p=0.07).
      CONCLUSIONS: Traffic calming has been shown to be effective in reducing the
      number of PVCs but needs to be supported by additional measures to further
      improve the safety of pedestrians.

PMID- 24300679
TI  - Laboratory tests for malaria: a diagnostic conundrum?
AB  - OBJECTIVES: To detect malarial parasites using the peripheral blood smear (PBS)
      and to compare the PBS with the immunochromatographic antigen test (i.e. OptiMAL
      and polymerase chain reaction (PCR)). METHODS: Six ml of blood was collected from
      each of 170 patients clinically suspected of having malaria. These samples were
      used to perform PBS examination, the OptiMAL test and PCR by standard protocol.
      RESULTS: PBS examination found malarial parasites in 86 (50.6%) samples. In
      comparison, 71 (41.8%) samples were positive by OptiMAL test whereas PCR could
      detect malarial parasites in only 44 (25.9%) samples. All 84 (49.4%) samples
      which were negative by PBS were negative by both OptiMAL and PCR. The sensitivity
      and specificity were respectively 85.54% and 100% for OptiMAL and 51.12% and 100%
      for PCR. CONCLUSION; Depending on the tests' operational feasibility, and the
      availability of adequate trained personnel, equipment and laboratory management
      systems, and considering its sensitivity and cost-effectiveness, peripheral blood
      smear remains the test of choice for malaria, especially in endemic areas.

PMID- 24300680
TI  - Patterns of seatbelt use in different socioeconomic communities in the Cape Town
      Metropole, South Africa.
AB  - BACKGROUND; Road traffic injuries are a leading cause of death and may be related
      to social inequality. OBJECTIVE: To establish whether patterns of seatbelt use
      vary between different socioeconomic communities in the Cape Town Metropole,
      South Africa. METHODS: Vehicles and their occupants at 7 high-volume crossings (3
      in high-income areas) were placed under surveillance for 2 hours each during
      November 2010. All occupants were eligible for inclusion except occupants of non
      motorised vehicles, two-wheel motorised vehicles, buses, taxis, heavy goods
      vehicles and emergency vehicles. Child seatbelt use was recorded only for
      children who appeared older than 3 years. RESULTS: A total of 4 651 vehicles with
      6 848 occupants were surveyed. Rates of seatbelt use were 45.1% (n=3 090) for all
      occupants, 54.0% (n=2 513) for drivers, 33.1% (n=521) for front-seat passengers
      (adults 33.2%, n=452; children 32.7%, n=69) and 9.0% (n=56) for rear-seat
      passengers (adults 4.0%, n=13; children 14.4%, n=43). Occupants from high-income
      areas were more likely to wear seatbelts (odds ratio (OR) 4.35; 95% confidence
      interval (CI) 3.89 - 4.88). Use of child restraints was poor overall (22.3%,
      n=114), but also varied according to income areas (high income 40.9%, n=99; low
      income 0.03%, n=6; OR 26.77; 95% CI 11.44 - 62.63). DISCUSSION: The impact of
      road traffic injuries is significant, but can be decreased by using appropriate
      restraining devices. Seatbelt use in South Africa, although compulsory, is
      neither strictly adhered to nor enforced. Their use is proportionally lower in
      lower-income areas. Specific interventions are required to target these
      communities directly.

PMID- 24300681
TI  - Paramedic rapid sequence induction (RSI) in a South African emergency medical
      service: a retrospective observational study.
AB  - BACKGROUND: Early access to critical care interventions may improve outcomes for
      severely ill and injured patients. South Africa (SA) faces the unique challenges
      of prolonged pre-hospital times and limited access to physicians. In 2008, the
      Health Professions Council of SA introduced paramedic rapid sequence induction
      (RSI), the gold standard critical care intervention for emergency airway
      management; however, the risk to benefit ratio in this context is unclear.
      OBJECTIVE: We conducted a pilot study to identify if paramedic RSI in the SA pre
      hospital care setting is effective and safe. METHODS: We undertook a
      retrospective observational study of paramedic RSI performed by an emergency
      medical service, between 12 December 2009 and 12 December 2011. RESULTS: Eighty
      six RSIs were performed during the study period. No failed intubations were
      reported. Heart rate was significantly reduced from a median baseline value of
      112 to 90 bpm, and oxygen saturations improved from 92% to 99% at handover
      following RSI. Nineteen patients (22%), however, had an adverse event (AE).
      Female patients (odds ratio (OR) 18.3; 95% confidence interval (CI) 3.46 - 99.38;
      p=0.001) and patients subsequently transported by helicopter (OR 7.24; 95% CI
      1.44 - 36.32; p=0.016) remained independently associated with AEs after adjusting
      for confounders. CONCLUSIONS: RSI performed by specially trained paramedics is
      effective in terms of self-reported success. However, the 1 in 5 AE rate
      highlights safety concerns. The importance of a robust clinical governance
      programme to identify problems, refine practice and improve the quality of care
      is underscored.

PMID- 24300682
TI  - Accuracy of after-hour 'red dot' trauma radiograph triage by radiographers in a
      South African regional hospital.
AB  - BACKGROUND: The global demand for diagnostic imaging exceeds the supply of
      radiologists and is of particular significance in poorly resourced healthcare
      environments where many radiographs are unreported. Delayed or absent reporting
      may negatively impact patient management. In well-resourced countries there is
      recognition that extending the role of radiographers to radiological reporting
      tasks helps meet service demands. Aim. To determine the accuracy of acute
      fracture detection by South African radiographers working in an after-hour
      setting. METHOD: We performed a retrospective study of radiographers at a Western
      Cape Regional Hospital over 2 months in 2011. The sensitivity and specificity of
      radiographers' fracture detection were compared with that of a consultant
      radiologist. Differences were evaluated using the McNemar chi-squared test, with
      p<0.05 regarded as significant. RESULTS: A total of 369 radiographs were
      analysed. The overall accuracy of reporting by radiographers was 93.7%, with
      74.4% sensitivity for fracture detection. Experienced radiographers performed
      better than inexperienced radiographers; adult fractures were more consistently
      identified than paediatric fractures, and appendicular fractures were better
      visualised than axial fractures. In all instances there was a significant
      difference between fracture detection by radiographers and the radiologist.
      Experienced radiographers evaluating appendicular fractures in adults achieved
      the highest sensitivity (89.9%), which was not significantly different from that
      of a consultant radiologist (p=0.88). CONCLUSION: The performance of experienced
      radiographers in our study is comparable with that of experienced radiographers
      internationally, who have no specific training in trauma radiograph reporting.
      However, additional training is required if role extension is to be considered.

PMID- 24300683
TI  - Endotracheal tube cuff pressures - the worrying reality: a comparative audit of
      intra-operative versus emergency intubations.
AB  - OBJECTIVES: The primary aim was to assess the need for objective cuff pressure
      monitoring in the theatre complex and trauma centre at Groote Schuur Hospital,
      Cape Town, South Africa. Secondary aims were to determine whether the tube size,
      tube make or place of intubation affected cuff pressure. METHOD: Endotracheal
      tube cuff pressures of 91 patients in the trauma centre and 100 patients in the
      theatre complex were randomly measured using a Mallinckrodt cuff pressure gauge.
      The measurements were recorded on a standardised data sheet and transferred to an
      electronic database for analysis. RESULTS: There was a significant difference
      between cuff pressures in the trauma centre and those in the theatre complex
      (p<0.001), the means being 55 cmH2O and 25 cmH2O, respectively. The site of
      intubation had a significant (p=0.001) effect on cuff pressures, with mean
      pressures as follows: on scene - 71 cmH2O; referral hospital - 57 cmH2O; and
      Groote Schuur trauma centre - 42 cmH2O. Only 30% of cuff pressures measured in
      the trauma centre were below 30 cmH2O, and, alarmingly, 17% were between 91 and
      120 cmH2O. In the theatre complex, 77% of cuff pressures were in the acceptable
      range. Digital balloon palpation corresponded poorly (correlation coefficient
      0.47) with measured cuff pressure, and statistical analysis showed that it tended
      to underestimate the pressure at higher cuff pressures. CONCLUSION: The risk of a
      high cuff pressure is roughly two- to threefold higher in emergency patients than
      in theatre patients. These unacceptably high cuff pressures are especially
      concerning in view of the fact that many trauma patients are hypotensive and
      therefore more susceptible to mucosal ischaemia.

PMID- 24300684
TI  - Outcomes following prehospital airway management in severe traumatic brain
      injury.
AB  - BACKGROUND: Prevention of hypoxia and thus secondary brain injury in traumatic
      brain injury (TBI) is critical. However there is controversy regarding the role
      of endotracheal intubation in the prehospital management of TBI. OBJECTIVE: To
      describe the outcome of TBI with various airway management methods employed in
      the prehospital setting in the Cape Town Metropole. METHODS: The study was a
      cohort descriptive observational analysis of 124 consecutively injured adult
      patients who were admitted for severe TBI (Glasgow Coma Score <=8) to Groote
      Schuur and Tygerberg hospitals between 1 January 2009 and 31 August 2011.
      Patients were categorised by their method of airway management: rapid sequence
      intubation (RSI), sedation-assisted intubation, failed intubation, basic airway
      management, and intubated without drugs. Good outcomes were defined by a Glasgow
      Outcome Score of 4 - 5. RESULTS: There was a statistically significant
      association between airway management and outcome (p=0.013). Patients who
      underwent basic airway management had a higher proportion of a good outcome
      (72.9%) than patients who were intubated in the prehospital setting. A good
      outcome was observed with 61.8% and 38.4% of patients who experienced sedation
      assisted intubation and RSI, respectively. Patients intubated without drugs had
      the poorest outcome (88%), followed by rapid sequence intubation (61.5%) and by
      the sedation assisted group (38.2%). CONCLUSION: Prehospital intubation did not
      demonstrate improved outcomes over basic airway management in patients with
      severe TBI. A large prospective, randomised trial is warranted to yield some
      insight into how these airway interventions influence outcome in severe TBI.

PMID- 24300685
TI  - The Kimberley Hospital Rule (KHR) for urgent computed tomography of the brain in
      a resource-limited environment.
AB  - BACKGROUND: The indications for urgent computed tomography of the brain (CTB) in
      the acute setting are controversial. While guidelines have been proposed for CTB
      in well-resourced countries, these are not always appropriate for resource
      limited environments. Furthermore, no unifying guideline exists for trauma
      related and non-trauma-related acute intracranial pathology. Adoption by resource
      limited countries of more conservative scanning protocols, with outcomes
      comparable to well-resourced countries, would have significant benefit. A
      multidisciplinary team from Kimberley Hospital in the Northern Cape Province of
      South Africa adopted the principles defined in the National Institute for Health
      and Care Excellence (NICE) guideline for the early management of head injury and
      drafted the Kimberley Hospital Rule (KHR), a proposed unifying guideline for the
      imaging of acute intracranial pathology in a resource-limited environment.
      OBJECTIVE: To evaluate the sensitivity and specificity of the KHR. METHODS: A
      prospective cohort study was conducted in the Northern Cape Province between 1
      May 2010 and 30 April 2011. All patients older than 16 years presenting to
      emergency departments with acute intracranial symptoms were triaged according to
      the KHR into three groups, as follows: group 1 - immediate scan (within 1 hour);
      group 2 - urgent scan (within 8 hours); and group 3 - no scan required. Patients
      in groups 1 and 2 were studied. The primary outcome was CTB findings of
      clinically significant intracranial pathology requiring acute change in
      management. RESULTS: Seven hundred and three patients were included. The KHR
      achieved 90.3% sensitivity and 45.5% specificity, while reducing the number of
      immediate CTBs by 36.0%. CONCLUSION: The KHR is an accurate, unifying clinical
      guideline that appears to optimise the utilisation of CTB in a resource-limited
      environment.

PMID- 24300686
TI  - Haemodialysis for post-traumatic acute renal failure - factors predicting
      outcome.
AB  - BACKGROUND: Post-traumatic acute renal failure requiring renal replacement
      therapy in an intensive care unit (ICU) is associated with high mortality.
      OBJECTIVE: To assess indicators of improved survival. METHODS: This was a
      retrospective cohort study of 64 consecutive trauma patients (penetrating and
      blunt trauma and burns) who underwent haemodialysis (HD) over a period of 5
      years. Information on pre-hospital and in-hospital resuscitation, trauma scores
      and physiological scores and daily ICU records were collected. The majority of
      the patients were dialysed with continuous venovenous haemofiltration in the
      early years of the study and later with sustained low-efficiency dialysis.
      RESULTS: Of the 64 patients 47 died, giving an overall mortality rate of 73%.
      Mortality was highest in the burns patients (84%). Survival in all patients,
      irrespective of injury, was unrelated to the Revised Trauma Score, Injury
      Severity Score, Acute Physiology and Chronic Health Evaluation Score or Trauma
      Injury Severity Score. The duration of HD did not differ significantly between
      the three trauma groups, and age was not a significant predictor of survival.
      Patients who were polyuric at the time of the initiation of HD had a lower
      mortality rate than those who were oliguric, anuric or normouric, although this
      did not reach statistical significance (p=0.09). CONCLUSIONS: Acute renal failure
      in trauma patients is associated with a low survival rate. Controversial
      conclusions have been presented in the literature. In this study, none of the
      parameters previously reported to affect survival proved to be valid, although
      the number of patients was comparable with those in other studies. Since
      understanding of the predictors and course of renal failure in trauma patients is
      still at an early stage, there is a need for multicentre prospective studies.

PMID- 24300687
TI  - Human fascioliasis in South Africa.
AB  - Human fascioliasis has the widest latitudinal, longitudinal and altitudinal
      distribution of any vector-borne disease, yet only 3 cases have been reported
      from South Africa, the last in 1964. We report 2 cases from the same geographic
      area associated with local consumption of watercress, suggesting an endemic
      focus.  

PMID- 24300688
TI  - Heart Failure Society of South Africa (HeFSSA) perspective on the European
      Society of Cardiology (ESC) 2012 chronic heart failure guideline.
AB  - BACKGROUND: The South African Heart Association (SA Heart) is an affiliate of the
      European Society of Cardiology (ESC). SA Heart endorses ESC treatment guidelines
      with modification to suit local circumstances. The Heart Failure Society of South
      Africa (HeFSSA) is a special interest group of SA Heart. This guideline has been
      compiled on behalf of the HeFSSA and is based on the ESC guidelines for the
      diagnosis and treatment of acute and chronic heart failure 2012. The focus is on
      heart failure with reduced ejection fraction (HF-REF) (i.e. ejection fraction
      <50%). We have recommended interventions in symptomatic patients with HF-REF in
      general to clarify the 'grey area' between the ESC guidelines definition of REF
      (<50%) and the predefined ejection fraction used in randomised heart failure
      trials (<35%). OBJECTIVE: To highlight new changes in the diagnosis and treatment
      of chronic heart failure with particular emphasis on areas that are relevant to
      SA. CONCLUSIONS: Randomised clinical trials are a crucial, but not the only,
      guide in treating HF-REF patients. There always remain questions that are
      unanswered and groups of patients not studied, so prudent clinical decisions are
      required.

PMID- 24300689
TI  - Guideline for the diagnosis and management of multiple sclerosis: a Southern
      African perspective.
AB  - Before making a diagnosis of multiple sclerosis (MS), it is imperative that
      alternative diagnoses are considered and excluded. This is particularly important
      in South Africa, which is a moderate prevalence MS area, has a high burden of
      neurological infections and where the majority of the people are black - an
      ethnic group that has a very low frequency of MS. Before applying diagnostic
      criteria, there should be no better explanation for the patient's presentation.
      This guideline, written on behalf of the Multiple Sclerosis Society of South
      Africa, aims to assist in the diagnosis and treatment of MS in Southern Africa.  

PMID- 24300690
TI  - Guideline for the diagnosis and management of multiple sclerosis in children.
AB  - Paediatric multiple sclerosis (MS) represents a particular MS subgroup with
      unique diagnostic challenges. Due to the narrow window of environmental exposures
      and clinical disease expression, children with MS may represent an important
      study population for gaining a better understanding of the pathogenesis of the
      disease. The International Paediatric MS Study Group (IPMSSG) was formulated to
      clarify the diagnostic and therapeutic dilemmas in this population. This
      guideline was adapted from the International Paediatric Multiple Sclerosis Study
      Group guideline and endorsed by PANDA, South Africa.  

PMID- 24300691
TI  - 'We don't see that in South Africa'.

PMID- 24300692
TI  - Ensuring equitable access to high quality care: the task of uplifting trauma care
      in rural and district hospitals.

PMID- 24300693
TI  - Plant defense after flooding.
AB  - Since the first study of hypoxic response in plants with cDNA microarray in 2002,
      the number of hypoxia-responsive genes has grown to more than 2000. However, to
      date, only small numbers of hypoxia-responsive genes are known to confer hypoxic
      resistance. Most investigations in this area have focused on identifying which
      genes are responsive and then characterized how these genes are induced during
      hypoxia, but the roles of numerous genes in hypoxic response are still unknown.
      In our recent study, we demonstrated that a group of genes are induced by
      submergence to trigger plant immunity, which is a response to protect plants
      against a higher probability of pathogen infection during or after flooding. This
      work offered a brand new perspective, i.e., that hypoxia-responsive genes can be
      induced for reasons other than conferring hypoxic resistance. Possible reasons
      why these responses were triggered are discussed herein. 

PMID- 24300694
TI  - The glial perspective of autism spectrum disorders.
AB  - The aetiology of autism spectrum disorders remains unclear although a growing
      number of associated genetic abnormalities and environmental factors have been
      discovered in recent decades. These advancements coincided with a remarkable
      increase in the comprehension of physiological functions and pathological
      potential of neuroglia in the central nervous system that led to a notion of
      fundamental contribution of glial cells into multiple neuropathologies, including
      neuropsychiatric and developmental disorders. Growing evidence indicates a role
      for deregulation of astroglial control over homeostasis and plastic potential of
      neural networks as well as microglial malfunction and neuroinflammatory response
      in the brains of autistic patients. In this review, we shall summarize the status
      and pathological potential of neuroglia and argue for neuroglial roots of
      autistic disorders. 

PMID- 24300695
TI  - Stress, serotonin, and hippocampal neurogenesis in relation to depression and
      antidepressant effects.
AB  - Chronic stressful life events are risk factors for developing major depression,
      the pathophysiology of which is strongly linked to impairments in serotonin (5
      HT) neurotransmission. Exposure to chronic unpredictable stress (CUS) has been
      found to induce depressive-like behaviours, including passive behavioural coping
      and anhedonia in animal models, along with many other affective, cognitive, and
      behavioural symptoms. The heterogeneity of these symptoms represents the
      plurality of corticolimbic structures involved in mood regulation that are
      adversely affected in the disorder. Chronic stress has also been shown to
      negatively regulate adult hippocampal neurogenesis, a phenomenon that is involved
      in antidepressant effects and regulates subsequent stress responses. Although
      there exists an enormous body of data on stress-induced alterations of 5-HT
      activity, there has not been extensive exploration of 5-HT adaptations occurring
      presynaptically or at the level of the raphe nuclei after exposure to CUS.
      Similarly, although hippocampal neurogenesis is known to be negatively regulated
      by stress and positively regulated by antidepressant treatment, the role of
      neurogenesis in mediating affective behaviour in the context of stress remains an
      active area of investigation. The goal of this review is to link the serotonergic
      and neurogenic hypotheses of depression and antidepressant effects in the context
      of stress. Specifically, chronic stress significantly attenuates 5-HT
      neurotransmission and 5-HT1A autoreceptor sensitivity, and this effect could
      represent an endophenotypic hallmark for mood disorders. In addition, by
      decreasing neurogenesis, CUS decreases hippocampal inhibition of the hypothalamic
      pituitary-adrenal (HPA) axis, exacerbating stress axis overactivity. Similarly,
      we discuss the possibility that adult hippocampal neurogenesis mediates
      antidepressant effects via the ventral (in rodents; anterior in humans)
      hippocampus' influence on the HPA axis, and mechanisms by which antidepressants
      may reverse chronic stress-induced 5-HT and neurogenic changes. Although data are
      as yet equivocal, antidepressant modulation of 5-HT neurotransmission may well
      serve as one of the factors that could drive neurogenesis-dependent
      antidepressant effects through these stress regulation-related mechanisms. 

PMID- 24300696
TI  - Identification of metabolically active bacteria in the gut of the generalist
      Spodoptera littoralis via DNA stable isotope probing using 13C-glucose.
AB  - Guts of most insects are inhabited by complex communities of symbiotic
      nonpathogenic bacteria. Within such microbial communities it is possible to
      identify commensal or mutualistic bacteria species. The latter ones, have been
      observed to serve multiple functions to the insect, i.e. helping in insect
      reproduction(1), boosting the immune response(2), pheromone production(3), as
      well as nutrition, including the synthesis of essential amino acids(4,) among
      others.     Due to the importance of these associations, many efforts have been
      made to characterize the communities down to the individual members. However,
      most of these efforts were either based on cultivation methods or relied on the
      generation of 16S rRNA gene fragments which were sequenced for final
      identification. Unfortunately, these approaches only identified the bacterial
      species present in the gut and provided no information on the metabolic activity
      of the microorganisms. To characterize the metabolically active bacterial species
      in the gut of an insect, we used stable isotope probing (SIP) in vivo employing
      (13)C-glucose as a universal substrate. This is a promising culture-free
      technique that allows the linkage of microbial phylogenies to their particular
      metabolic activity. This is possible by tracking stable, isotope labeled atoms
      from substrates into microbial biomarkers, such as DNA and RNA(5). The
      incorporation of (13)C isotopes into DNA increases the density of the labeled DNA
      compared to the unlabeled ((12)C) one. In the end, the (13)C-labeled DNA or RNA
      is separated by density-gradient ultracentrifugation from the (12)C-unlabeled
      similar one(6). Subsequent molecular analysis of the separated nucleic acid
      isotopomers provides the connection between metabolic activity and identity of
      the species. Here, we present the protocol used to characterize the metabolically
      active bacteria in the gut of a generalist insect (our model system), Spodoptera
      littoralis (Lepidoptera, Noctuidae). The phylogenetic analysis of the DNA was
      done using pyrosequencing, which allowed high resolution and precision in the
      identification of insect gut bacterial community. As main substrate, (13)C
      labeled glucose was used in the experiments. The substrate was fed to the insects
      using an artificial diet. 

PMID- 24300697
TI  - Functional outcomes of maltreated children and adolescents in a community-based
      rehabilitation program in Brazil: six-month improvement and baseline predictors.
AB  - This study sought to implement outcomes monitoring and to review outcome data
      from a community-based rehabilitation program for maltreated children and
      adolescents in Sao Paulo, Brazil. Maltreated children and adolescents (N=452)
      were enrolled in The Equilibrium Program (TEP), a multidisciplinary community
      based rehabilitation program. About half (n=230) of the participants were
      successfully evaluated using the Children's Global Assessment Scale (C-GAS) at
      entry, 3, and/or 6 months later. Analysis of outcomes used hierarchical linear
      modeling of functional change from baseline. With a baseline C-GAS score of 51.7
      (SD=14.22), average improvement was 2.8 and 5.5 points at 3 and 6 months,
      respectively (reflecting small to moderate effect sizes=0.20 and 0.39).
      Improvement was associated with Problems related to upbringing (p<.02) at entry
      and absence of Physical abuse (p<.05) and Negative life events in childhood
      (p<.05) but was not associated with sociodemographics or any specific psychiatric
      diagnosis. This study showed that outcomes monitoring is feasible in a community
      based program in a developing country. Although there was no untreated control
      group for comparison and specific evidence-based treatments were not used, it is
      notable that significant improvement, with small to moderate effect size, was
      observed. 

PMID- 24300698
TI  - [Experimental assessment of biodegradable polyglycolic and polylactic acid
      polymers for medical use].
AB  - Interrelations of biodegradable poliglicolic and polilactic acid polymers in
      various proportions implanted in standardized bone defects were evaluated in
      animal model with 40 Wister line rats. During 10 month follow-up period bone
      capsule surrounded all implants, but timing of bone formation and bone quality
      varied significantly being optimal in LactoSorb group. Destructive features of
      polymers were also seen in implant-bone contact area defined as inflammation,
      fibrous tissue formation and cell dystrophy. 

PMID- 24300699
TI  - [Comparative evaluation of antimicrobial activity of root canal irrigation
      agents].
AB  - A comparative study of the antimicrobial activity of different antiseptics for
      root canal irrigation: chlorhexidine bigluconate solution in 6 concentrations
      (2.0-1.0-0.5-0.2-0.1-0.02%), two sodium hypochlorite formulations: "Parcan"
      (France) and "Hypochloran-3" (Russia), and stabilized EDTA solution (EDTA
      Solutions (Korea)) was carried out. The results indicate that the level of
      antimicrobial activity of chlorhexidine is directly proportional to its
      concentration. Sodium hypochlorite tends to be more effective in compare with
      chlorhexidine. EDTA Solutions has a pronounced antimicrobial activity against all
      strains. 

PMID- 24300700
TI  - [Xerostomia and means that facilitate its symptoms].
AB  - There are a number of reasons that lead to inadequate salivation or complete
      cessation of salivation. Among others, one of the main can be systemic diseases
      like Sjogren's syndrome, and the use of medication and radiation therapy. When
      affected by Xerostomia, oral mucosa requires constant moisturizing. Medicaments
      stimulating saliva secretion and moisturizers for oral mucosa alleviate symptoms
      in most of the cases. LABORATORIOS KIN S.A. is a Spanish company offering a mouth
      moisturizing products' line, among others, KIN HIDRAT toothpaste and KIN HIDRAT
      spray with a formulation close to natural saliva. 

PMID- 24300701
TI  - [Clinical and morphological features of odontogenic keratocysts].
AB  - Clinical, histological and immunohystochemical studies of keratocystic tumors
      were performed showing differences in proliferative activity and MMP-9 expression
      scores in orthokeratinized and parakeratinised cysts. These histological features
      are associated with clinical course and may be used as markers for recurrence
      probability. 

PMID- 24300702
TI  - [Autofibroblasts in surgical treatment of periodontal disease].
AB  - Effectiveness of periodontal disease surgical treatment using hydroxyapatite with
      gingival autofibroblasts culture was assessed in the study by clinical and
      laboratory data. 

PMID- 24300703
TI  - [Endoscopic and laboratory data in diagnostics of traumatic TMJ lesions].
AB  - Twenty-seven patients with various types of internal TMJ disorders were examined
      at Voronezh Dental School Oral and Maxillofacial Surgery Department. All the
      patients underwent comprehensive examination and double-circuit TMJ arthroscopy,
      as well as joint fluid sampling for subsequent biochemical studies. A correlation
      between the degree of pathological changes of the TMJ intraarticular structures
      and biochemical parameters in traumatic TMJ lesions was discovered. The patterns
      observed may serve as a useful tool for more accurate diagnostics and treatment
      planning. 

PMID- 24300704
TI  - [Age associated clinical features of odontogenic maxillary sinusitis].
AB  - Detailed analysis of odontogenic maxillary sinusitis clinical course allowed
      identifying clinical features of the disease specific for elderly and senile
      patients. The paper describes the peculiarities of odontogenic maxillary
      sinusitis in elderly and senile patients including those having oroantral sinus
      tract. 

PMID- 24300705
TI  - [Adaptive dentoalveolar changes by insufficient sizes of the jaws].
AB  - The study is based on analysis of 1800 CT scans performed in patients undergoing
      orthodontic treatment in Samara dental clinic "Orthodont" from 2007 to 2012.
      Various adaptive dentoalveolar changes by insufficient sizes of the jaws were
      identified and classified in 4 groups: (1) adaptation of teeth position
      associated with jaw size insufficiency; (2) adaptation of alveolar bone
      associated with jaw size insufficiency; (3) adaptation of teeth position
      associated with muscle balance; (4) adaptation of teeth associated with space
      deficiency by their development. Hence adaptive changes involve all dentoalveolar
      structures influencing orthodontic treatment planning. Some of the changes may
      not be corrected. 

PMID- 24300706
TI  - [Treatment of significant parotid ducts deformities].
AB  - The paper summarizes authors experience in treatment of 14 patients with
      congenital parotid ducts deformities (megastenon type). The results showed
      reconstructive surgical treatment to be sufficiently effective in such cases. If
      restoration of parotid function is not possible one should consider interventions
      for secretion reduction and duct walls excision. 

PMID- 24300707
TI  - [Use of metabolic drugs and psychotherapy in dental implantation in elderly
      patients].
AB  - The estimation of efficiency of metabolic drugs and psychotherapy in dental
      implantation in the elderly was carried out. On the basis of the study results an
      important pathogenetic significance of use of metabolic drug cytoflavin and
      cognitive therapy in the treatment of partially adentia at elderly patients was
      justified. It was proved that the optimization of the internal picture of health
      by means of the implementation of information and regulatory functions, and
      emotional reinforcement of the therapeutic process in patients receiving
      cytoflavin and cognitive therapy would improve the effectiveness of the
      treatment, to increase "survival" performance of implants and to approach to
      understanding the underlying mechanisms of forming health in elderly patients
      with partial adentia. 

PMID- 24300708
TI  - [Anatomical and radiological studies on additional mandible teeth anesthesia
      considering innervation variability].
AB  - The paper presents studies on nutritional foramina of the mandible. Some
      nutritional foramina located in the frontal mandibular region on the lingual
      surface and containing significant blood vessels and nerves are found to be more
      typical for teeth-bearing mandible. In retromolar area in case of third molars
      presence intraosseous canals were revealed leading to inferior alveolar nerve
      canal. One should consider intraligamental and lingual anesthesia by lower
      incisors extraction. Intraosseous anesthesia and retromolar area infiltration
      significantly increase anesthesia efficiency by third molar extraction. 

PMID- 24300709
TI  - [Method of customized analysis of tension deformities in fixed dental
      restorations].
AB  - The paper presents the technique for transporting CT and CAD 3D-modelling data in
      software for tension deformities analysis with the possibility for customizing
      physical properties of certain anatomical structures and constructive materials.
      The obtained data allowed performing analyzing of tension deformities of dental
      restorations in ANSYS software. 

PMID- 24300710
TI  - [Radiological evaluation of transverse maxillofacial disparity].
AB  - Graphical model is established based on frontal cephalometric for differential
      diagnostic of transverse morphological and functional abnormalities of the
      mandible. Eight graphical models are made which cover and dinstinguish possible
      transverse variations of mandible position and morphology taking into account the
      asymmetry of the mandible, rotation and translation of the joints and the
      combinations thereof. With these eight detailed models an orthodontist can
      accurately differentiate the problem and choose an adequate treatment plan. 

PMID- 24300711
TI  - Improved detection of gastrointestinal pathogens using generalised sample
      processing and amplification panels.
AB  - We aimed to streamline the diagnosis of gastrointestinal disease by producing
      multiplexed real time polymerase chain reaction (PCR) panels employing universal
      sample processing for DNA and RNA containing pathogens. A total of 487 stored,
      previously characterised stool samples comprising bacterial, viral, protozoan and
      Clostridium difficile positive samples were tested using four multiplexed real
      time PCR panels. A further 81 pre-selected clinical samples from a teaching
      hospital were included to provide an independent validation of assay performance.
      Improved sensitivity was achieved using the protozoan panels and 16 more mixed
      infections were observed compared to tests with conventional methods. Using the
      C. difficile panels, 100% sensitivity was achieved when compared to the gold
      standard of toxigenic culture. In addition, hypervirulent strains including
      ribotype 027 could be identified directly from primary sample without the need
      for ribotyping methods. Bacterial and viral panels detecting Salmonella,
      Shigella, Campylobacter, Yersinia enterocolitica, Listeria monocytogenes,
      norovirus groups I and II, rotavirus A, astrovirus, sapovirus, rotavirus B,
      adenovirus and adenovirus 40/41 performed as well as conventional methods, whilst
      allowing detection in 3 hours from processing to result. Multiplex real time PCR
      panels with universal sample preparation allow streamlined, rapid diagnosis of
      gastrointestinal pathogens whilst extending the characterisation of pathogens
      present in stool samples from affected patients.

PMID- 24300713
TI  - Diagnostic validation of a familial hypercholesterolaemia cohort provides a model
      for using targeted next generation DNA sequencing in the clinical setting.
AB  - Our aim was to assess the sensitivity and specificity of a next generation DNA
      sequencing (NGS) platform using a capture based DNA library preparation method.
      Data and experience gained from this diagnostic validation can be used to
      progress the applications of NGS in the wider molecular diagnostic setting. A
      technical cross-validation comparing the current molecular diagnostic gold
      standard methods of Sanger DNA sequencing and multiplex ligation-dependant probe
      amplification (MLPA) versus a customised capture based targeted re-sequencing
      method on a SOLiD 5500 sequencing platform was carried out using a cohort of 96
      familial hypercholesterolaemia (FH) samples. We compared a total of 595 DNA
      variations (488 common single nucleotide polymorphisms, 73 missense mutations, 9
      nonsense mutations, 3 splice site point mutations, 13 small indels, 2 multi
      exonic duplications and 7 multi-exonic deletions) found previously in the 96 FH
      samples. DNA variation detection sensitivity and specificity were both 100% for
      the SOLiD 5500 NGS platform compared with Sanger sequencing and MLPA only when
      both LifeScope and Integrative Genomics Viewer softwares were utilised. The
      methods described here offer a high-quality strategy for the detection of a wide
      range of DNA mutations in diseases with a moderate number of well described
      causative genes. However, there are important issues related to the bioinformatic
      algorithms employed to detect small indels.

PMID- 24300714
TI  - Molecular and cellular analysis of three novel alpha2-globin gene promoter
      mutations [HBA2: c.-59C>T], [HBA2: c.-81C>A] and [HBA2: c.-91G>A] reveal varying
      patterns of transcriptional and translational activities.
AB  - While point mutations affecting the promoter region of beta-globin gene are
      widely described, there are no well characterised reports of any point mutations
      currently found in the promoter of the alpha2-globin (HBA2) gene. We present
      clinical and experimental data for three novel HBA2 gene core and proximal
      promoter mutations. Using an in vitro system designed to assess the impact of
      point mutations, the three novel [HBA2:c.-59C>T], [HBA2:c.-81C>A] and [HBA2:c.
      91G>A] promoter mutations identified in three unrelated patients were analysed
      for HBA2 gene transcriptional and translational activities. Following the
      generation and transfection of expression vectors carrying each mutation, the
      HBA2 transcription activity of the promoters from each mutant was analysed with
      quantitative real time-PCR (qReTi-PCR) technique. Immunofluorochemistry (IFC) was
      used to analyse HBA2 protein synthesis. The analyses showed that [HBA2:c.-59C>T]
      and [HBA2:c.-91G>A] mutant constructs caused significant reduction in the HBA2
      transcription levels by 53.7% (p = 0.0008) and 36.2% (p = 0.004), respectively,
      resulting in markedly lower HBA2 protein labelling when compared to the wild type
      as shown with subsequent IFC analysis. Conversely, the [HBA2:c.-81C>A] construct
      showed no significant changes in either transcription (p = 0.089) or in protein
      labelling when compared to the wild type. The equal pAmp transcription levels
      found in each group confirmed that the observed labelling differences were not
      due to varying transfection efficiencies. This study emphasises the importance of
      in vitro studies to establish the impact of base substitutions on the level of
      gene expression, and the value of these studies in clinicopathological
      correlation so that appropriate advice can be given in genetic counselling.

PMID- 24300712
TI  - Cognitive deficit and autism spectrum disorders: prospective diagnosis by array
      CGH.
AB  - The aim of this study was to determine prospectively the frequency of pathogenic
      chromosomal microdeletions and microduplications in a large group of referred
      patients with developmental delay (DD), intellectual disability (ID) or autism
      spectrum disorders (ASD) within a genetic diagnostic service. First tier testing
      was applied using a standardised oligo-array comparative genomic hybridization
      (CGH) platform, replacing conventional cytogenetic testing that would have been
      used in the past. Copy number variants (CNVs) found to be responsible for the
      clinical condition on the request form could all be subdivided into three groups:
      well established pathogenic microdeletion/microduplication/aneuploidy syndromes,
      predicted pathogenic CNVs as interpreted by the laboratory, and recently
      established pathogenic disease susceptibility CNVs. Totalled from these three
      groups, with CNVs of uncertain significance excluded, detection rates were: DD
      (13.0%), ID (15.6%), ASD (2.3%), ASD with DD (8.2%), ASD with ID (12.7%) and
      unexplained epilepsy with DD, ID and ASD (10.9%). The greater diagnostic
      sensitivity arising from routine application of array CGH, compared with
      previously used conventional cytogenetics, outweighs the interpretative issues
      for the reporting laboratory and referring clinician arising from detection of
      CNVs of uncertain significance. Precise determination of any previously hidden
      molecular defect responsible for the patient's condition is translated to
      improved genetic counselling.

PMID- 24300715
TI  - Development of a silver in situ hybridisation based assay for the determination
      of ploidy status in molar pregnancy diagnosis.
AB  - The aim of this study was to establish a scoring method for ploidy analysis using
      silver in situ hybridisation (SISH) with a chromosome 17 centromere probe. SISH
      was performed using the Ventana chromosome 17 centromere probe on sections from
      formalin fixed, paraffin embedded archival cases of complete hydatidiform moles,
      partial hydatidiform moles and hydropic products of conception with previously
      established ploidy status (determined by flow cytometry or karyotyping). In order
      to determine ploidy status, a scoring method was developed based on both the
      average number of signals per nucleus (ASN) and the percentage of nuclei with
      three signals (N3S), enumerated in 50 villous cytotrophoblastic and/or stromal
      cells. The results of four independent observers were compared individually and
      collectively with previously established ploidy status. There was a highly
      statistically significant difference between diploid and triploid gestations for
      ASN (1.86 +/- 0.13 and 2.70 +/- 0.16 respectively, Student t-test, p < 0.0001)
      and for N3S (1.14 +/- 1.65 and 71.59 +/- 14.25 respectively, Student t-test, p <
      0.0001). The sensitivity and specificity of the SISH-based assay was 99.1% and
      100% respectively for ASN, and 100% and 100% respectively for N3S. A chromosome
      17 centromere probe SISH-based assay can reliably distinguish between diploid and
      triploid gestations. This test has diagnostic utility in distinguishing partial
      hydatidiform moles from histological mimics.

PMID- 24300716
TI  - Fascin expression predicts lymph node metastasis and worse survival in small
      intestinal carcinoma.
AB  - Fascin expression has been associated with clinicopathological parameters and
      clinical outcome in many carcinomas. The aim of this study was to evaluate the
      prognostic impact of fascin expression in small intestinal carcinomas (SICs). We
      constructed tissue microarrays for evaluation of immunohistochemical expression
      of fascin in a total of 194 SICs. Fascin was expressed in 47 (24.2%) of the 194
      SICs, and fascin expression showed an association with poorly and
      undifferentiated histology (p < 0.001) and lymphatic invasion (p = 0.019). No
      fascin expression was observed in tumour cells of metastatic lymph nodes in cases
      of SIC without fascin expression (p < 0.001). Patients with fascin expression
      showed significantly shorter overall survival compared to patients without
      expression (p = 0.001). In multivariate analysis, fascin expression was an
      independent prognostic factor in SIC patients (p = 0.043). Fascin expression
      showed significant correlation with lack of differentiation and lymphatic
      invasion, and may be a useful predictive marker for lymph node metastasis. Fascin
      expression in SICs showed an association with poor overall survival and was an
      independent poor prognostic factor.

PMID- 24300717
TI  - Increased c-Met phosphorylation is related to keloid pathogenesis: implications
      for the biological behaviour of keloid fibroblasts.
AB  - Keloid is induced by a pathological wound healing response, and hepatocyte growth
      factor (HGF) is known to be involved in tissue repair via the activation of its
      primary receptor, c-Met. We aimed to investigate whether c-Met activation is
      implicated in keloid pathogenesis. HGF, c-Met, phosphorylated c-Met (p-Met), Ki
      67, collagen I protein, and MET gene expression were detected in five normal skin
      and 30 keloid tissues by immunohistochemistry and quantitative real-time
      polymerase chain reaction analysis, respectively. The influence of p-Met
      expression on the biological behaviour of keloid fibroblasts was further
      investigated with regard to cell proliferation, motility, invasiveness, collagen
      I expression, and intracellular signaling in vitro. p-Met protein and MET gene
      expression but not HGF or c-Met protein expression showed significant increases
      in keloid tissues than dermal layer of normal skin tissues. In keloid tissues, p
      Met expression was significantly associated with keloid size, Ki-67 and collagen
      I expression. Moreover, p-Met expression was also related to proliferation,
      migration, invasiveness, collagen I expression and activation of AKT and Erk in
      keloid fibroblasts in vitro. c-Met activation may have a strong influence on
      keloid pathogenesis, and it can be investigated further as a potential molecular
      target for keloid therapy.

PMID- 24300718
TI  - Detection of hepatitis B virus DNA in serum is rare in the absence of hepatitis B
      surface antigen: impacts for detection and monitoring of chronic hepatitis B.

PMID- 24300719
TI  - Activity of ceftaroline against community associated and healthcare associated
      methicillin resistant Staphylococcus aureus.

PMID- 24300720
TI  - Osseous metaplasia in polypoid rectal mucosal prolapse.

PMID- 24300721
TI  - Plasmablastic lymphoma presenting as a colonic stricture in Crohn's disease.

PMID- 24300722
TI  - 5-Alpha reductase inhibitors and PSA screening for prostate cancer.

PMID- 24300723
TI  - BRAF V600E mutation specific immunohistochemistry with clone VE1 is not reliable
      in pituitary adenomas.

PMID- 24300724
TI  - A change in the molecular epidemiology of vancomycin resistant enterococci in
      Western Australia.

PMID- 24300725
TI  - A low grade PIN-like neoplasm of the transition zone immunohistochemically
      negative for basal cell markers: a possible example of low grade adenocarcinoma
      with stratified epithelium.

PMID- 24300726
TI  - EGFR gene copy number alterations are not a useful screening tool for predicting
      EGFR mutation status in lung adenocarcinoma.
AB  - We investigated if gene copy number (GCN) alterations of the epidermal growth
      factor receptor (EGFR), as detected by silver enhanced in situ hybridisation
      (SISH), could be used to select patients for EGFR mutation testing. Resected lung
      adenocarcinoma specimens with adequate tumour were identified. EGFR SISH was
      performed using the Ventana Benchmark Ultra platform. EGFR GCN was classified
      according to the Colorado Classification System. EGFR mutations were scanned by
      high resolution melting and confirmed by Sanger sequencing. Thirty-four of 96
      tumours were EGFR SISH positive (35%), and 31 of 96 tumours harboured one or more
      EGFR mutations (32%). Of 31 EGFR-mutant tumours, 18 were EGFR SISH positive
      (58%). There was a statistically significant relationship between the presence of
      an EGFR mutation and EGFR GCN (p = 0.003). Thirteen of 31 EGFR-mutant tumours
      were EGFR SISH negative (42%), and 16 of 65 EGFR-wild type tumours were EGFR SISH
      positive (24%). The sensitivity, specificity, positive predictive value and
      negative predictive value were 58%, 75%, 52.9% and 79%, respectively. Despite a
      significant relationship between EGFR GCN alterations and EGFR mutations, our
      results indicate that EGFR GCN as detected by SISH is not a suitable way to
      select patients for EGFR mutation testing.

PMID- 24300727
TI  - Long term outcome of primary urothelial papilloma: a single institution cohort.
AB  - The aim of this study was to investigate the long term outcome of primary
      urothelial papilloma (UP). We retrieved 41 primary UP, diagnosed between January
      2000 and December 2009. Follow-up was obtained by searching pathology and
      clinical electronic databases. Mean patient age was 57 years (range 30-84 years),
      with a male-to-female ratio of 1.9:1. Mean follow-up was 81 months (range 3-127
      months). In 37 (90.2%) patients, no recurrence and/or progression were documented
      and no subsequent higher grade neoplasms were diagnosed. Three male patients were
      diagnosed with UP at 1, 31, and 43 months after the initial resection; the repeat
      diagnosis of UP at 1 month likely represented an incomplete resection. Thus, only
      two of 41 patients (4.9%) had a recurrent UP. One of these patients had a
      subsequent papillary urothelial neoplasm of low malignant potential (PUNLMP), 17
      months after the recurrent UP (48 months after the initial UP). Only one
      additional male had a subsequent PUNLMP, 76 months after the initial UP. Thus,
      only two of 41 patients (4.9%) had a subsequent PUNLMP, both presenting with
      haematuria. Primary UP does not progress to UC when diagnosed using strict
      criteria, when no previous or concurrent neoplasms are documented, and when
      complete initial resection is performed.

PMID- 24300728
TI  - Complement C3 and its polymorphism: biological and clinical consequences.
AB  - Complement 3 (C3) is a crucial component of the innate immune system, which in
      association with other complement proteins, forms a major host mechanism for
      detection and clearance of potential pathogens. The central role of the
      complement system and its polymorphism has already been studied extensively.
      Although the identification of C3 in echinoderms and tunicates suggests that this
      multifunctional protein emerged at least 700 million years ago, the underlying
      functional difference between C3S and C3F variants have not yet been clearly
      demonstrated. Focussing on the examined associations between C3F and C3S
      polymorphisms and disease states, the presence of the C3F allele has generally
      been linked with a detrimental outcome. In this review the general
      characteristics and analytical aspects of C3 and the knowledge about the
      biological and clinical consequences of C3 polymorphism have been summarised.

PMID- 24300729
TI  - Clinical significance of cancer in radical prostatectomy specimens: analysis from
      a contemporary series of 2900 men.
AB  - With prostate specific antigen (PSA) testing, up to 49% of detected tumours are
      small and in some of these cases there is a possibility that the tumour will
      remain clinically insignificant during the patient's remaining lifetime. The
      current study was performed to characterise the extent of cancer in men treated
      by radical prostatectomy (RP) in a community without population-based PSA
      screening. Clinical and pathological data of 2900 patients who underwent RP
      between 2008 and 2012 were analysed. Specimens were entirely embedded and
      evaluated by routine haematoxylin and eosin staining. Tumours were graded using
      recent modifications to the International Society of Urological Pathology (ISUP)
      modified Gleason grading system, and staged according to the ISUP
      recommendations. Tumours were considered pathologically insignificant if organ
      confined, with a volume of <0.5  cc and a Gleason score (GS) of <7. The mean age
      of patients in the series was 63 years (range 32-79 years) and the mean pre
      operative PSA was 7.16  ng/mL (range 0.4-69). In total, 2614 (90.1%) were
      classified as cT1; however, insignificant tumours were found in only 150 (5.2%)
      patients following examination of the radical prostatectomy specimen. A total of
      2681 cases (92.4%) had a final GS of >=7, 1144 (39.4%) had extraprostatic
      extension (EPE), of which 88.7% were classified as established; 669 (23.1%) had a
      tumour volume of >3  cc and 284 (9.8%) had surgical margin positivity. Seminal
      vesicle involvement was seen in 159 (5.5%) cases. Of 693 patients who had a
      lymphadenectomy, 31 (4.5%) had lymph node metastases. Aged <=50 years were 212
      (7.3%) patients (mean age 47 years). Of these, 194 were classified as cT1 while
      192 (90.6%) were found to have significant cancer on examination of the radical
      prostatectomy specimen. We have shown in our series that although 90.1% of
      tumours were cT1, an overwhelming majority of tumours were found to be
      pathologically significant following RP, with a high proportion of cases showing
      high stage disease, seminal vesicle involvement and lymph node metastasis. These
      results suggest that, contrary to estimates from international trials, ad hoc PSA
      testing is associated with low levels of over-treating.

PMID- 24300730
TI  - 5-Alpha reductase inhibitors and PSA screening for prostate cancer.

PMID- 24300731
TI  - Chronic myeloid leukaemia masquerading as primary myelofibrosis.

PMID- 24300732
TI  - Myxoid variant of adrenocortical carcinoma: a report of two illustrative cases
      and a brief review of the literature.

PMID- 24300733
TI  - Bilateral, multicentric low-grade adenosquamous carcinomas of the breast, each
      arising within a separate radial scar/complex sclerosing lesion.

PMID- 24300734
TI  - Design, synthesis and evaluation of dual pharmacology beta2-adrenoceptor agonists
      and PDE4 inhibitors.
AB  - A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated
      as dual pharmacology beta2-adrenoceptor agonists and PDE4 inhibitors. Most of the
      hybrids displayed high beta2-adrenoceptor agonist and moderate PDE4 inhibitory
      activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50=1.05nM,
      pEC50=9.0) and potent PDE4B2 inhibitory activities (IC50=0.092MUM). 

PMID- 24300736
TI  - Synthesis and biological evaluation of novel N-substituted 1H
      dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential
      antimicrobial agents.
AB  - A series of new N-substituted 1H-dibenzo[a,c]carbazole derivatives were
      synthesized from dehydroabietic acid, and their structures were characterized by
      IR, (1)H NMR and HRMS spectral data. All compounds were evaluated for their
      antibacterial and antifungal activities against four bacteria (Bacillus subtilis,
      Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens) and three
      fungi (Candida albicans, Candida tropicalis and Aspergillus niger) by serial
      dilution technique. Some of the synthesized compounds displayed pronounced
      antimicrobial activity against tested strains with low MIC values ranging from
      0.9 to 15.6MUg/ml. Among them, compounds 6j and 6r exhibited potent inhibitory
      activity comparable to reference drugs amikacin and ketoconazole. 

PMID- 24300737
TI  - Stereoselective total synthesis of a novel regiomer of herbarumin I and its
      cytotoxic and antimicrobial activities.
AB  - Stereoselective synthesis of a novel regiomer of the natural nonenolide,
      herbarumin I has been accomplished. The synthesis involves the coupling of the
      alcohol and acid fragments of the molecule using Yamaguchi protocol followed by
      intramolecular ring closing metathesis. The cytotoxic and antimicrobial
      properties of the synthetic regiomer have been studied. 

PMID- 24300735
TI  - Design of small molecule epigenetic modulators.
AB  - The field of epigenetics has expanded rapidly to reveal multiple new targets for
      drug discovery. The functional elements of the epigenomic machinery can be
      categorized as writers, erasers and readers, and together these elements control
      cellular gene expression and homeostasis. It is increasingly clear that
      aberrations in the epigenome can underly a variety of diseases, and thus
      discovery of small molecules that modulate the epigenome in a specific manner is
      a viable approach to the discovery of new therapeutic agents. In this Digest, the
      components of epigenetic control of gene expression will be briefly summarized,
      and efforts to identify small molecules that modulate epigenetic processes will
      be described. 

PMID- 24300738
TI  - Neural circuit recording from an intact cockroach nervous system.
AB  - The cockroach ventral nerve cord preparation is a tractable system for
      neuroethology experiments, neural network modeling, and testing the physiological
      effects of insecticides. This article describes the scope of cockroach sensory
      modalities that can be used to assay how an insect nervous system responds to
      environmental perturbations. Emphasis here is on the escape behavior mediated by
      cerci to giant fiber transmission in Periplaneta americana. This in situ
      preparation requires only moderate dissecting skill and electrophysiological
      expertise to generate reproducible recordings of neuronal activity. Peptides or
      other chemical reagents can then be applied directly to the nervous system in
      solution with the physiological saline. Insecticides could also be administered
      prior to dissection and the escape circuit can serve as a proxy for the excitable
      state of the central nervous system. In this context the assays described herein
      would also be useful to researchers interested in limb regeneration and the
      evolution of nervous system development for which P. americana is an established
      model organism. 

PMID- 24300739
TI  - Update on vitamin D during childhood.
AB  - PURPOSE OF REVIEW: We propose to review several recent key clinically oriented
      topics related to vitamin D and health in children. RECENT FINDINGS: We found a
      very large number of recent clinical studies related to vitamin D. However, most
      are association studies with few physiological or clinical trials that are
      adequately powered for clinical outcomes. Key results are available related to
      pulmonary disease and allergic disorders. Recent studies have also evaluated the
      relationship of vitamin D to bone health as well as new insights into genetic
      conditions related to vitamin D metabolism. SUMMARY: Recent studies generally
      support the recommendations of the Institute of Medicine related to vitamin D
      intake but there is new and increasing evidence that some health conditions, such
      as pulmonary diseases in children, might benefit from close monitoring of vitamin
      D status. However, controlled trials are mostly lacking and there is an
      inadequate basis from recent studies to recommend high dose vitamin D pending the
      results of controlled trials.

PMID- 24300740
TI  - New treatment targets for the management of irritable bowel syndrome.
AB  - PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) and chronic idiopathic
      constipation (CIC) are highly prevalent medical conditions that reduce quality of
      life and represent a substantial economic burden on healthcare cost. Until
      recently, no specific treatment options were available. This review will provide
      an update of the most recent randomized clinical trials data showing efficacy and
      safety of novel, targeted treatment modalities in IBS and CIC with
      gastrointestinal receptor and ion channel agonists. RECENT FINDINGS: Recent
      discoveries of peptides and small molecules targeting gastrointestinal receptors
      and ion channels resulted in novel, specific pharmacological therapies of IBS and
      CIC. The bicyclical fatty acid lubiprostone and the synthetic 14-amino acid
      peptide linaclotide were identified to selectively activate a Chloride Channel-2
      and the Guanylin Cyclase-C receptor, respectively, and demonstrate efficacy in
      the treatment of IBS with constipation and CIC. SUMMARY: Novel molecules
      including the bicyclical fatty acid lubiprostone and the synthetic 14-amino acid
      peptide linaclotide represent new treatment modalities for IBS with constipation
      and CIC with proven efficacy and acceptable side-effect profiles.

PMID- 24300741
TI  - Endocrinology, epigenetics, and environment.

PMID- 24300742
TI  - Ligamentum flavum hematomas of the cervical and thoracic spine.
AB  - OBJECTIVE: To report extremely rare cases of ligamentum flavum hematomas in the
      cervical and thoracic spine. Only six cases of thoracic ligamentum flavum
      hematomas and three cases of cervical ligamentum flavum hematomas have been
      reported so far. METHODS: Two patients presented with tetraparesis and one
      patient presented with radicular pain and paresthesias in the T3 dermatome. MRI
      was performed in two patients, which showed a posterior intraspinal mass,
      continuous with the ligamentum flavum. The mass was moderately hypointense on T2
      weighted images and hyperintense on T1-weighted images with no contrast
      enhancement. The third patient underwent cervical myelography because of a
      cardiac pacemaker. The myelography showed an intraspinal posterior mass with
      compression of the dural sac at C3/C4. RESULTS: All patients underwent a
      hemilaminectomy to resect the ligamentum flavum hematoma and recovered completely
      afterwords, and did not experience a recurrence during follow-up of at least 2
      years. CONCLUSION: This case series shows rare cases of ligamentum flavum
      hematomas in the cervical and thoracic spine. Surgery achieved complete recovery
      of the preoperative symptoms in all patients within days.

PMID- 24300743
TI  - Ruptured, fusiform, distal lenticulostriate aneurysm causing intraventricular
      haemorrhage in a patient with antiphospholipid-negative Sneddon's syndrome.

PMID- 24300744
TI  - Chiari I malformation associated with Gorham's disease of the skull base.

PMID- 24300745
TI  - Autologous dural substitutes: a prospective study.
AB  - OBJECTIVE: Duraplasty can be performed both by means of autologous tissues (such
      as galea-pericranium, temporal muscle, fascia lata) or by commercially available
      dural patches. Nowadays many neurosurgeons consider galea-pericranium duraplasty
      time-consuming, technically demanding or not adequate, thus dural surrogates are
      increasingly popular. In this prospective research we compared duraplasty using
      autologous galea-pericranium vs. dural patches in terms of postoperative long
      term results, ease/time required and costs. PATIENTS AND METHODS: Research has
      been designed as prospective cohort study, that included 185 patients undergoing
      supratentorial elective neurosurgery with galea-pericranium or non-autologous
      duraplasty (minimum follow-up 12 months). Variables taken into account were:
      wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis,
      brain abscess, empyema and tardive wound dehiscence (particularly after
      postoperative radiotherapy). Time for galea-pericranium collection, size of galea
      pericranium harvest and dural defects were recorded in each case. Costs for non
      autologous duroplasty were calculated. RESULTS: No statistically significant
      differences were evident in long term postoperative results between the two
      groups. Mean time of galea-pericranium collection is less than 2min and enough
      galea-pericranium can be harvested in supratentorial approach to cover almost any
      dural defect. The only difference between the two groups is costs: an average of
      268.7?/patient spent just for duraplasty. This figure is surely substantial if
      considered for the entire amount of surgeries performed in a department.
      CONCLUSIONS: Considering that in our study long term results are equivalent, that
      galea-pericranium duraplasty is feasible and rapid, our indications are in favor
      of saving a considerable amount of money since an ideal autologous dural
      substitute is available and "free".

PMID- 24300746
TI  - Analysis of contact interfaces for single GaN nanowire devices.
AB  - Single GaN nanowire (NW) devices fabricated on SiO2 can exhibit a strong
      degradation after annealing due to the occurrence of void formation at the
      contact/SiO2 interface. This void formation can cause cracking and delamination
      of the metal film, which can increase the resistance or lead to a complete
      failure of the NW device. In order to address issues associated with void
      formation, a technique was developed that removes Ni/Au contact metal films from
      the substrates to allow for the examination and characterization of the
      contact/substrate and contact/NW interfaces of single GaN NW devices. This
      procedure determines the degree of adhesion of the contact films to the substrate
      and NWs and allows for the characterization of the morphology and composition of
      the contact interface with the substrate and nanowires. This technique is also
      useful for assessing the amount of residual contamination that remains from the
      NW suspension and from photolithographic processes on the NW-SiO2 surface prior
      to metal deposition. The detailed steps of this procedure are presented for the
      removal of annealed Ni/Au contacts to Mg-doped GaN NWs on a SiO2 substrate. 

PMID- 24300748
TI  - Obstetrics and gynecology clerkship for males and females: similar curriculum,
      different outcomes?
AB  - OBJECTIVE: To determine if performance differences exist between male and female
      students on a 6-week obstetrics and gynecology (Ob/Gyn) clerkship and to evaluate
      potential variables that might underlie any observed variations. STUDY DESIGN:
      Final clerkship grades and component scores (clinical evaluations, objective
      structured clinical examination [OSCE], oral examination, and National Board of
      Medical Examiners [NBME] subject examination) from July 2007 to June 2010 were
      matched by student and analyzed by gender. Basic science grade point average
      (GPA) and initial United States Medical Licensing Exam (USMLE) Step 1 scores were
      used to establish students' baseline medical knowledge. On a post-clerkship
      questionnaire, a subset of students reported the numbers of procedures they
      performed during the clerkship; students also completed online pre- and post
      clerkship questionnaires reflecting their self-assessed confidence in women's
      health clinical skills. RESULTS: Scores were analyzed for 136 women and 220 men.
      Final clerkship grades were significantly higher for females than for males
      (89.05 vs. 87.34, p=0.0004, eta(2)=0.08). Specifically, females outscored males
      on the OSCE, oral, and NBME subject examination portions of the clerkship but not
      clinical evaluations. Males reported completing fewer breast examinations
      (p=0.001, eta(2)=0.14). Pre-clerkship, males were significantly less confident
      than females in women's health clinical skills (p<0.01) but reached similar
      levels upon completion of the clerkship. No gender differences were detected for
      basic science GPA and USMLE Step 1 scores. CONCLUSION: Student gender is
      associated with final grades on an Ob/Gyn clerkship. Further research regarding
      these differences should be explored.

PMID- 24300749
TI  - A comparison of two scales for assessing health professional students' attitude
      toward interprofessional learning.
AB  - RATIONALE: The validated 19-item Readiness for Interprofessional Learning Scale
      (RIPLS) is often used for assessing attitudes toward interprofessional education
      (IPE). The 12-item Interdisciplinary Education Perception Scale (IEPS), also used
      for this purpose, has not been validated among the professions of medicine,
      pharmacy, and physician assistants (PAs). The discriminatory ability of the two
      scales has not been directly compared. Comparison of the two will aid educators
      in selecting the optimal scale. OBJECTIVE: To compare psychometric properties of
      the RIPLS and IEPS and to examine the ability of each scale to discriminate mean
      scores among student subgroups (gender, profession, seniority, and prior IPE
      exposure). METHOD: We conducted a cross-sectional (Qualtrics((c))) survey (RIPLS
      and IEPS) of junior and senior students in medicine (n=360), pharmacy (n=360),
      and the PA profession (n=106). Descriptive statistics were used to report
      aggregate mean scores of subgroups. The internal consistency of each scale was
      assessed using Cronbach's alpha. Concurrent validity was measured by Pearson's
      correlation coefficients. Independent-sample t-tests and analysis of variances
      (ANOVAs) were performed to assess the discriminatory ability of each scale.
      Cohen's d effect sizes were calculated for all significant pair-wise comparisons.
      RESULTS: Response rate was 82%. Cronbach's alpha was 0.85 (RIPLS) and 0.91
      (IEPS). The RIPLS discriminated scores by gender among junior students only, and
      scores by IPE exposure among all students. The IEPS distinguished score
      differences for the three professions among junior students and by prior IPE
      exposure for all three professions. Neither scale detected differences in mean
      scores by profession among all students or by level of training among the three
      professions. CONCLUSIONS: Neither the RIPLS nor the IEPS has greater
      discriminatory ability for detecting attitude differences among the student
      subgroups. Reason for differences may be explained by slightly different scale
      constructs. The RIPLS is designed to assess students' own attitude toward
      interprofessional learning, while the IEPS discerns perceived attitudes about
      team collaboration for students' own professions and may be more appropriate for
      more advanced students.

PMID- 24300750
TI  - Growing neural stem cells from conventional and nonconventional regions of the
      adult rodent brain.
AB  - Recent work demonstrates that central nervous system (CNS) regeneration and
      tumorigenesis involves populations of stem cells (SCs) resident within the adult
      brain. However, the mechanisms these normally quiescent cells employ to ensure
      proper functioning of neural networks, as well as their role in recovery from
      injury and mitigation of neurodegenerative processes are little understood. These
      cells reside in regions referred to as "niches" that provide a sustaining
      environment involving modulatory signals from both the vascular and immune
      systems. The isolation, maintenance, and differentiation of CNS SCs under defined
      culture conditions which exclude unknown factors, makes them accessible to
      treatment by pharmacological or genetic means, thus providing insight into their
      in vivo behavior. Here we offer detailed information on the methods for
      generating cultures of CNS SCs from distinct regions of the adult brain and
      approaches to assess their differentiation potential into neurons, astrocytes,
      and oligodendrocytes in vitro. This technique yields a homogeneous cell
      population as a monolayer culture that can be visualized to study individual SCs
      and their progeny. Furthermore, it can be applied across different animal model
      systems and clinical samples, being used previously to predict regenerative
      responses in the damaged adult nervous system. 

PMID- 24300751
TI  - Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study
      in patients with schizophrenia.
AB  - Weight gain represents a frequent side effect of antipsychotic drug treatment.
      The current trial investigated the effect of add-on treatment with sibutramine in
      schizophrenia outpatients who had gained more than 7% of weight during the course
      of treatment. This 24-week placebo-controlled study evaluated the effects of
      sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio,
      BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several
      laboratory tests were performed. Psychopathological symptoms and side effects
      were assessed frequently. Fifteen patients were assigned randomly to add-on
      treatment with sibutramine 10 mg or placebo. The two groups did not differ in
      weight, sociodemographic, or clinical data. Eleven patients were considered for
      statistical analysis. Significant weight loss was observed in the sibutramine
      group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight
      gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in
      the placebo group. No significant between-group differences were found in changes
      in psychopathology or drug safety. This pilot trial suggests that adjunctive
      treatment with sibutramine may be safe and effective in schizophrenic patients
      with antipsychotic-induced weight gain.

PMID- 24300752
TI  - [Secondary operations for the treatment of nasal septum deformities].
AB  - The objective of the present retrospective study was to improve the methods of
      secondary surgical intervention for the treatment of nasal septum (NS)
      deformations and evaluate their immediate outcomes. A series of 56 re-operations
      on NS is represented. Two main approaches to the treatment of secondary
      deformation were applied: repeated septoplasty with autocartilage and bone re
      implantation and tissue-preserving endoscopic submucous resection of deviated
      septal portions. Endoscopic studies, CT of the nasal cavity and paranasal
      sinuses, anterior active rhinomanometry, and acoustic rhinometry were used to
      clarify the character of deformation and to objectively assess the resulting
      disorders of nasal breathing. The differential approach to the choice of the
      surgical correction strategy made it possible to restore nasal breathing in all
      40 patients followed up during 3 months after re-operation. The results of
      anterior active rhinomanometry indicate that the mean total volumetric flow
      increased after the secondary treatment from the initial value of 467.7+/
      89.1cm3/s to 901.1+/-115.4 cm3/s within the following three months. The cases of
      postoperative perforation or the development of other possible complications were
      not documented. 

PMID- 24300753
TI  - [The phenomenon of vascular microthrombosis in mucoperichondrium associated with
      plastic closure of nasal septum perforations].
AB  - The objective of the present study was to identify specific hematological
      features characterizing the pathophysological processes of clinical significance
      associated with plastic closure of nasal septum perforations. Changes of
      clinical, biochemical, and coagulation-related blood characteristics developing
      as a result of the surgical treatment of the patients with ENT pathology were
      analysed. It was shown that D-dimer is a specific hematological characteristic
      that reflects the phenomenon of postoperative vascular microthrombosis in
      mucoperichondrial-periosteal flaps associated with plastic closure of nasal
      septum perforations. Based on the results of this study, the authors recommend to
      prescribe low-molecular weight heparins for prophylactic purposes to the patients
      undergoing plastic closure of nasal septum perforations. 

PMID- 24300754
TI  - [The effectiveness of specific immunotherapy of allergic diseases of respiratory
      organs from the standpoint of evidence-based medicine. The results of a 5-year
      retrospective study].
AB  - The objective of this first Ukrainian 5-year retrospective study was to
      subjectively evaluate the effectiveness of specific immunotherapy (sublingual and
      injection) of the upper respiratory tract in the patients presenting with
      seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), SAR and PAR
      with polyvalent sensitization. The analysis of the results of sublingual,
      injection, and combined specific immunotherapy given to 750 patients allowed to
      describe them as "excellent" and "good" in the groups with PAR (83% of the total
      number), SAR (93%), SAR and PAR with polyvalent sensitization (84%). 

PMID- 24300755
TI  - [The effectiveness of long-term treatment of polypous rhinosinusitis with low
      doses of macrolides].
AB  - The objective of the present study was to estimate the effectiveness of the long
      term treatment with low doses of macrolides for the prevention of early relapses
      of polypous rhinosinusitis in the postoperative period. A total of 66 patients at
      the age from 18 to 77 years presenting with the clinical diagnosis of bilateral
      polypous rhinosinusitis were randomly allocated to 3 groups; fifty five patients
      completed the study. All the patients underwent endoscopic polysinusotomy. All of
      them were given basal therapy with mometasone furoate at a daily dose of 400 mcg
      throughout 6 month postoperative period. The patients of groups 1 (n=22) and 2
      (n=14) additionally received daily doses of 25 mg clarithromycin during 6 and 3
      months respectively. The patients of group 3 were given basal therapy alone. All
      the patients were followed up within 6, 12, and 24 weeks after surgery with the
      use of a visual-analog scale, SNOT-20 questionnaire, acoustic rhinometry and
      rhinomanometry, endoscopic study of the nasal cavity, computed tomography of
      paranasal sinuses, determination of saccharine transport time, evaluation of
      olfactorial sense, and measurement of the eosinophilic cationic protein level in
      the nasal secretion. It was demonstrated that the patients treated with
      clarithromycin show significantly better outcomes of therapy compared with
      controls (p<0.05), the effectiveness of the 6 month clarithromycin therapy being
      higher than that of the 3 month treatment. The exception was the results of
      estimation of clinical symptoms and signs based on the visual-analog scale and
      the acoustic rhinometric data that did not reveal significant differences between
      the groups. The patients of the control group given no clarithromycin
      significantly more frequently developed relapses of polypous rhinosinusitis
      (p=0.02). 

PMID- 24300756
TI  - [The influence of radiofrequency thermal ablation on the clinical course of
      hypertrophic rhinitis and histomorphology of the inferior turbinated bones].
AB  - The objective of the present work was to study the influence of radiofrequency
      thermal ablation (RFTA) of the inferior turbinated bones on the main functions of
      the nasal cavity in the patients suffering hypertrophic rhinitis. The secondary
      objective was to elucidate the histomorphological features of the inferior
      turbinated bones. A total of 40 patients presenting with nasal breathing
      disorders associated with the inferior turbinated bone hypertrophy were available
      for the examination. This work was supplemented by an experimental study with the
      use of rabbit the inferior turbinated bones. The influence of radiofrequency
      thermal energy on the hypertrophic the inferior turbinated bones was estimated
      based on dynamics of clinical symptoms and functional state of the nasal cavity
      before and after its application. The patients' complaints and the results of the
      objective evaluation were analysed and compared with the help of the visual
      analog scale (VAS) before and 1-8 weeks after RFTA. The study has demonstrated
      that the size of the inferior turbinated bones and the severity of nasal
      obstruction significantly decreased within 28 days after RFTA whereas the
      patients' complaints of nasal stiffness and difficulty of nasal breathing totally
      disappeared. The inferior turbinated bones of the rabbits underwent a marked
      reduction of density and cilia growth in conjunction with the thickening of the
      basal membrane and the onset of subepithelial fibrosis within 7 days after RFTA.
      The structure of basal membrane was virtually normalized within 28 days after
      RFTA simultaneously with a rise in the number of cilia and the enhancement of
      their growth. It is concluded that the results of clinical and experimental
      studies give reason to consider RFTA as an effective method for the treatment of
      nasal stiffness caused by hypertrophy of the inferior turbinated bones. RFTA
      induces subepithelial fibrosis and thereby promotes the decrease of the inferior
      turbinated bone volume in the absence of persistent damage to the surface
      epithelium and basal membrane. 

PMID- 24300757
TI  - [Peculiarities of hearing prosthetics for the patients suffering tympanophonia].
AB  - The objective of the present study was to estimate the influence of fractal tones
      (ZEN program) on chronic subjective tympanophonia in the patients using hearing
      aid apparatuses. A total of 20 subjects at the age from 30 to 69 years suffering
      tympanophonia in combination with grade I-IV loss of hearing were available for
      examination with the use of the following methods: analysis of complaints and
      medical histories, evaluation of ENT functioning, impedancometry, tonal
      threshold, suprathreshold and speech audiometry, psychoacoustic noise
      measurement, analysis of THI and TRQ questionnaires. The results of the
      questionnaire studies show that the use of the ZEN program and hearing aid
      apparatuses (Mind 440, WIDEX) decreased the intensity of tympanophonia in 90% of
      the patients. The therapeutic effect of the ZEN program in the younger patients
      was higher than in the elder ones. The probability of positive action of fractal
      tones decreased with increasing scores when the assessment was based on the
      primary THI and TRQ questionnaires. 

PMID- 24300758
TI  - [An experimental study of the coagulating properties of a laser beam applied to
      fix titanium prostheses of auditory ossicles with the use of platelet-rich
      plasma].
AB  - The displacement of prostheses of auditory ossicles at the concluding stage of
      surgery and in the early postoperative period is one of the factors influencing
      the functional outcome of stapedoplasty. The objective of the present
      experimental study was to estimate the effectiveness of the use of platelet-rich
      plasma as an alloy for the laser welding in order to improve fixation of titanium
      prostheses employed in ossiculoplastic surgery. The results of a series of
      experiments undertaken to assess the possibility of stabilization of titanium
      prostheses in the desired position with the help of laser welding indicate that
      this technique with the use of platelet-rich plasma as an alloy may be a reliable
      method for the fixation of the reconstructed chain of ossicles in the desired
      position. 

PMID- 24300759
TI  - [The influence of external factors on the auditory function in the students
      residing in a megapolis].
AB  - The objective of the present study was to estimate the auditory function in the
      students aged from 20 to 30 years and the noise load associated with the use of
      mobile phones, listening to music through headphones, attending concerts and
      youth clubs. The secondary objective was to assess the influence of these factors
      on the auditory function depending on their type, intensity, and duration. It is
      shown that the auditory threshold in the frequency range between 125 and 8000 Hz
      in 97% of the examined students do not exceed 25 dB varying from 5 to 15 dB The
      main factor influencing the auditory function is the use of players and
      headphones followed by mobile phones and deafening music in youth clubs. 

PMID- 24300760
TI  - [The multidisciplinary approach to diagnostics and treatment of hypervascular
      masses in ENTstructures].
AB  - The objective of the present work was to improve the quality of diagnostics and
      treatment of hypervascular masses in ENT structures based on the
      multidisciplinary approach. The study involved 51 patients presenting with
      hypervascular masses in ENT structures. All of them underwent comprehensive
      medical examination including fibrolaringoscopy, multispiral computed tomography,
      magnetic resonance tomography, ultrasound dopplerography, selective carotid
      angiography, and/or various combinations of these techniques. The patients were
      given surgical, endovascular, and combined treatments. The study has demonstrated
      the advantages of application of the multidisciplinary approach to combined
      diagnostics and treatment of hypervascular masses in ENT structures as
      exemplified by neck hemangioma. 

PMID- 24300761
TI  - [The role of regional intra-arterial chemotherapy in the combined treatment of
      locally advanced laryngeal cancer].
AB  - The objective of the present study was to estimate the possibilities and
      prospects for the use of regional intra-arterial chemotherapy in the combined
      treatment of locally advanced laryngeal cancer. The results of the
      chemoradiotherapeutic treatment of 26 patients presenting with locally advanced
      laryngeal cancer were analysed. The chemical agents were selectively administered
      intra-arterially three times from the right-hand femoral access by the standard
      procedure at a total focal dose (TFD) of 26 and 50 gram prior to the onset of and
      during of radiotherapy. The very first administration of the chemical agent
      resulted in the 30% decrease the tumour size. It further decreased by 70% on the
      average after the TFD of 50 gram was achieved. It made possible the continuation
      of gamma-therapy up to the total therapeutic dose. As a result, complete
      regression of the tumour was documented. The dynamic endoscopic control study and
      CT of the larynx revealed recurrent laryngeal cancer in 1 of the 26 patients
      (3.8%). The remaining patients did not develop metastases during the 18 month
      follow-up period. It is concluded that the results of the present study confirm
      high (96.2%) effectiveness of the method employed in this study which allows it
      to be recommended for the organ-preserving treatment of locally advanced
      laryngeal cancer. 

PMID- 24300762
TI  - [The functional status of the upper respiratory tract in the long-term smokers].
AB  - The objective of the present study was to evaluate the functional status of the
      upper respiratory tract in 50 long-term smokers based on the results of
      comprehensive medical examination, determination of mucociliary transport time,
      endoscopic study of the oral cavity and nasopharynx, anterior active
      rhinomanometry, computed tomography of the nasal cavity and paranasal sinuses,
      fibroendoscopic study of the larynx, and stroboscopy. It was shown that the most
      significant changes in the nasal cavity were associated with various forms of
      chronic rhinitis whereas chronic catarrh and hyperplastic laryngitis caused the
      most pronounced changes in the larynx. 

PMID- 24300763
TI  - [The prevalence of different Streptococcus pneumoniae serotypes in the children
      presenting with ENT infections or carrying nasopharyngeal pathogens].
AB  - The objective of the present study was to elucidate the etiopathological
      significance of various Streptococcus pneumoniae serotypes in the children
      presenting with ENT infections and carrying nasopharyngeal pathogens. The
      incidence of the latter condition was 19.5% in the children free from S.
      pneumoniae infection in comparison with 20.9% and 30.7% in those having diagnosis
      of otitis media and rhinosinusitis respectively. Fifty five (88.8%) of the 62
      isolated streptococcal strains were grouped into types with the use of multiplex
      PCR. Twelve serotypes were identified in the patients presenting with
      rhinosinusitis with the predominance of 6A/6B and 3 (40.5%) compared with seven
      isolated from the carriers of nasopharyngeal pathogens. In this group, type 3
      also prevailed (26.5%) whereas other serotypes occurred less frequently: 23F
      (13,4%), indivisible totality of 8, 9V, 9A, 1F, 11A, 211B, 11C, 11D, 12F, 15A,
      and 33F (13.4%), 20 (6.7%), 19A (6.7%), 14 (6.7%), 6A,6B (6.7%). The serotypes of
      S. pneumoniae isolated from the patients with rhinosinusitis were found to show
      55.3% identity with those present in the composition of the conjugated 7-valent
      pneumococcal vaccines, 63.2% identity with the 10-valent vaccine, 81.6% identity
      with the 11p-valnet vaccine, and 84.2% identity with the 13-valent vaccine. 

PMID- 24300764
TI  - [Halitosis concomitant with chronic ENT pathology in children].
AB  - The objective of the present study was to estimate the potential of gas
      chromatography as a tool for diagnostics of chronic ENT pathology in the
      children. A total of 37 patients aged between 5 and 18 years with chronic ENT
      diseases and complaints of foul breath were available for the examination. Thirty
      one children presented with chronic tonsillitis, 3 with chronic adenoiditis, 2
      with chronic rhinosinusitis, and 1 with subatrophic rhinitis. It was shown with
      the use of gas chromatography that the exhaled air from 34 (91.9%) patients
      contained cadaverin at a concentration of 0.004-0.0009 mg/ml. Three (8.1%)
      children exhaled methyl mercaptan (0.01-0.025 mg/m3) and hydrogen sulfide (0.002
      0.006 mg/m3), and 2 (5.4%) patients exhaled the air containing dimethyl disulfide
      (0.009-0.002 mg/m3). The volatile sulfur-containing compounds were detected only
      in the children aged above 14 years. It is concluded that chronic tonsillitis is
      the leading etiological factor responsible for the development of the extraoral
      form of halitosis in the children. The foul breath in the children unlike that in
      the adults is most frequently due to the enhanced cadaverin concentration in the
      exhaled air rather than the production of volatile sulfur-containing compounds. 

PMID- 24300765
TI  - [The frequency of chlamydial infection in the children attending pre-school
      institutions].
AB  - The objective of the present study was to estimate the prevalence and specific
      features of chlamydial infection within an organized group of children of pre
      school age. The data concerning the frequency of chlamydial infection of the
      upper respiratory tract in the children attending pre-school facilities are
      reported. The species composition of identified Chlamydia depending on the sex of
      the children is described. It is shown that acute and chronic ENT pathology in
      the patients presenting with chlamydial infection occurs much more frequently
      than in the unaffected children. These results were obtained during the
      examination of 121 children. Chlamydia was identified by means of the direct
      immunofluorescence technique. 

PMID- 24300766
TI  - [Comprehensive diagnostics of the patients presenting with Eustachian tube
      dysfunction].
AB  - The objective of the present work was comprehensive diagnostics of Eustachian
      tube dysfunction as exemplified by 82 patients with this disorder. The
      examination using the standard techniques was supplemented by active anterior
      rhinomanometry, audiometry, and tympanometry. Three-dimensional computed
      tomography (3D X-ray CT) was used for detailed diagnostics of the state of the
      nasal structures and paranasal sinuses. The study has demonstrated that 96.3% of
      the patients with Eustachian tube dysfunction suffer a concomitant pathology of
      the paranasal sinuses, nasal cavity, and nasopharynx. Difficulties of nasal
      breathing were experienced by 62% of the patients. 

PMID- 24300767
TI  - [Septoplasty in the children].
AB  - The objective of the present study was to improve the effectiveness of surgical
      intervention for the correction of the deflected nasal septum in the children.
      The clinical evaluation of the state of 63 patients and the follow-up study
      demonstrated that the early removal of the pack from the nasal cavity improves
      the patients' quality of life in the postoperative period and leads to as
      favourable outcome as the late removal. The application of still mineral water (a
      weakly alkaline sodium bicarbonate solution) for the irrigation or moistening of
      the nasal cavity mucosa promoted its rapid regeneration and wound healing. 

PMID- 24300768
TI  - [Local therapy of infectious complications of allergic rhinitis in the children].
AB  - The objective of the present investigation was to estimate the effectiveness and
      safety of rinorin used for the prevention and treatment of infectious
      complications of allergic rhinitis in the children. A total of 70 children
      varying in the age from 5 to 15 years and presenting with the mild and moderate
      to-severe form of seasonal allergic rhinitis were included in the study; they
      were divided into two groups. The study failed to reveal statistically
      significant difference between the groups in terms of adverse reactions to the
      treatment with rinorin. During the 21 day study period, infectious rhinitis was
      diagnosed in 2 (5.7%) children given rinorin compared with 5 (14.3%) ones in the
      control group (p>0.05). However, the patients of the latter group suffered a more
      severe form of this infectious complication of allergic rhinitis. It is concluded
      that rinorin is characterized by a high level of safety even though the
      antimicrobial potency of benzalkonium chloride, its active ingredient, needs
      further studies and evaluation. 

PMID- 24300769
TI  - [Peculiar features of mastoiditis in a brest-fed infant with the "exposed" facial
      nerve].
AB  - This paper reports the clinical case of mastoiditis in a 5-month old child in
      whom an unusual localization of the totally "naked" facial nerve outside of the
      bone canal in the mastoid part was discovered intraoperatively. This finding was
      quite unexpected because nerves are not visible on CT scanograms. The author
      emphasizes that the clinical course of otitis media in the breast- fed infants
      and young children is characterized by a number of peculiarities due to specific
      anatomical, physiological, and immunological features of the child's organism.
      She also notes that the number of antromastoidotomies for the treatment of
      mastoiditis has increased in Tatarstan during the recent years. 

PMID- 24300770
TI  - [The rare case of detection of long-term and asymptomatic presence of a foreign
      body (propylene filament) in the larynx].

PMID- 24300771
TI  - Implementation of a routine HIV testing policy in an acute medical setting in a
      UK general hospital: a cross-sectional study.
AB  - OBJECTIVES: To report the implementation and outcomes of a routine opt-out HIV
      testing policy in an acute medical unit (AMU) of a district general hospital in
      an area of high diagnosed HIV prevalence. METHODS: Since July 2011, all patients
      aged 16-79 years attending AMU were offered an HIV test as a hospital policy.
      Consenting and arranging the test was carried out by general medical staff, with
      training and motivational support by local HIV specialists. A retrospective cross
      sectional review was conducted: testing rate and outcomes of those testing HIV
      seropositive were determined by review of hospital data systems and case notes.
      RESULTS: Over a 21-month period, there were 12 682 admissions; 4122 (32.5%) had
      HIV tests. 20 patients (0.48%) were diagnosed with HIV; 17 (85%) of them were new
      diagnoses. Compared with those patients targeted as a result of clinical
      suspicion of HIV (n=6), patients who were diagnosed solely due to the scheme
      (n=14) had higher baseline CD4 counts (median 111 vs 313 cells/mm(3); p=0.01).
      Two patients had renal disease which improved on antiretroviral therapy. Two long
      term defaulters to HIV care with very advanced disease have re-engaged resulting
      in excellent clinical outcomes. 11 patients are now on treatment with
      undetectable HIV viral loads. One contact tested HIV positive. CONCLUSIONS: Our
      experience shows that routine opt-out testing can be delivered and sustained by
      general medical staff in an AMU with no money spent other than laboratory
      processing of the test. We believe that success and sustainability of this policy
      is due to the high level of commitment from and ownership by the AMU staff,
      particularly nurses. Ongoing support and motivation from the HIV team has
      facilitated the delivery of this policy.

PMID- 24300772
TI  - ECD kidneys and re-transplantation.

PMID- 24300773
TI  - Prevalence of cervical high-risk human papillomavirus infections in kidney graft
      recipients.
AB  - BACKGROUND: Female kidney graft recipients are regarded as a group at risk of
      cervical cancer development. The objective of this study was to assess the
      prevalence of cervical high-risk human papilloma virus (HR-HPV) infection and
      cervical intraepithelial neoplasia (CIN) in female kidney graft recipients in
      comparison to healthy controls. MATERIAL AND METHODS: We assessed the prevalence
      of HR-HPV and CIN in 60 female kidney graft recipients of reproductive age in
      outpatient care of the First Department of Obstetrics and Gynecology, Medical
      University of Warsaw. The control group consisted of 60 healthy women. Cervical
      swabs were analyzed with use of Amplicor HPV Roche Molecular Systems test,
      detecting DNA of 13 types of high-risk HPV: 6, 18, 31, 33, 35, 39, 45, 51, 52,
      56, 58, 59, and 68. RESULTS: HR-HPV was detected in 11/60 kidney recipients and
      15/60 healthy women (p=0.37). There was no correlation between HR-HPV presence
      and immunosuppressive regimen, underlying disease, graft function, or time
      interval from transplantation. In both groups, higher prevalence of HR-HPV was
      observed in females with >=2 lifetime sexual partners. Abnormal Pap test results
      in 2 kidney recipients (2 cases of HSIL) and 2 healthy women (LSIL and HSIL)
      required colposcopy-guided cervical biopsy, which in all cases revealed CIN2+.
      CONCLUSIONS: Female kidney graft recipients seem to be equally exposed to
      cervical infection with HPV of high oncogenic potential as the healthy
      population.

PMID- 24300776
TI  - The relationship between knee pain characteristics and symptom state
      acceptability in people with knee osteoarthritis.
AB  - OBJECTIVE: To examine the association between osteoarthritis (OA) pain
      characteristics and symptom acceptability. DESIGN: Using a cross-sectional study
      design in a knee OA cohort we assessed socio-demographics, knee pain
      characteristics (Intermittent and Constant Osteoarthritis Pain (ICOAP); higher
      scores worse), frequency of intermittent pain 'without warning' (unpredictable)
      or 'after a trigger' (predictable) (never to very often) and the acceptability of
      knee pain symptoms (yes/no). Using logistic regression, we examined the
      relationship between pain characteristics and symptom acceptability. RESULTS: 136
      cohort members' participated (mean age 74 years, SD 9.5; 54% female). Most (97%)
      reported intermittent pain (mean ICOAP intermittent score 36.8, SD 19.7) and 62
      (46%) reported constant pain (mean ICOAP constant score 46.7, SD 20.2). Of those
      with intermittent pain, 42% reported frequent (often/very often) predictable pain
      and 27% frequent unpredictable pain. 35% reported "unacceptable" knee symptoms.
      In multivariable analysis, the odds of reporting an unacceptable symptom state
      increased with increasing intermittent knee pain scores and the effect was
      greater for those with vs without frequent unpredictable intermittent pain
      (adjusted OR per 10-point increase in ICOAP intermittent score 3.31, 95%
      confidence interval (CI) 1.38-7.97 vs 1.23, 95%CI 0.88-1.74, respectively; P
      value for the interaction = 0.03). CONCLUSION: In a community cohort with
      symptomatic knee OA, both the severity and predictability of intermittent knee
      pain contributed to symptom state acceptability. Unpredictable intermittent knee
      pain was more likely to be associated with an unacceptable symptom state than
      predictable intermittent pain. Research is warranted to elucidate potentially
      modifiable determinants of unpredictable intermittent pain in people with knee
      OA.

PMID- 24300777
TI  - Characterization of electrode materials for lithium ion and sodium ion batteries
      using synchrotron radiation techniques.
AB  - Intercalation compounds such as transition metal oxides or phosphates are the
      most commonly used electrode materials in Li-ion and Na-ion batteries. During
      insertion or removal of alkali metal ions, the redox states of transition metals
      in the compounds change and structural transformations such as phase transitions
      and/or lattice parameter increases or decreases occur. These behaviors in turn
      determine important characteristics of the batteries such as the potential
      profiles, rate capabilities, and cycle lives. The extremely bright and tunable x
      rays produced by synchrotron radiation allow rapid acquisition of high-resolution
      data that provide information about these processes. Transformations in the bulk
      materials, such as phase transitions, can be directly observed using X-ray
      diffraction (XRD), while X-ray absorption spectroscopy (XAS) gives information
      about the local electronic and geometric structures (e.g. changes in redox states
      and bond lengths). In situ experiments carried out on operating cells are
      particularly useful because they allow direct correlation between the
      electrochemical and structural properties of the materials. These experiments are
      time-consuming and can be challenging to design due to the reactivity and air
      sensitivity of the alkali metal anodes used in the half-cell configurations,
      and/or the possibility of signal interference from other cell components and
      hardware. For these reasons, it is appropriate to carry out ex situ experiments
      (e.g. on electrodes harvested from partially charged or cycled cells) in some
      cases. Here, we present detailed protocols for the preparation of both ex situ
      and in situ samples for experiments involving synchrotron radiation and
      demonstrate how these experiments are done. 

PMID- 24300778
TI  - Celiac disease and preterm and/or low birthweight births.
AB  - Celiac disease (CD) is a genetically determined autoimmune condition, with an
      estimated worldwide prevalence of 1%. CD may be diagnosed or undiagnosed, but is
      usually identified through tests of specific antibodies and duodenal endoscopy.
      Treatment is the elimination of gluten from the diet. This article reviews six
      studies examining the relationship between CD and preterm (PTB) and/or low birth
      weight (LBW) births. Women previously identified with CD had pregnancy outcomes
      similar to women without CD. Undiagnosed CD, however, was associated with LBW in
      four of the six studies, and PTB in two studies. No increase in PTB or LBW birth
      was found in two studies. In these review of the literature, undiagnosed CD was
      most likely to result in increased risk of PTB or LBW. Nurses, nurse midwives,
      and nurse practitioners can play an important role in identifying and educating
      women with CD in the preconception and prenatal periods as well as during well
      woman health visits to potentially reduce PTB and LBW births in women with CD. 

PMID- 24300779
TI  - Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in
      Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a late-life neurodegenerative disease.
      Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H
      pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows
      structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      OBJECTIVES: In 2002 and 2007, we demonstrated elevated blood harmane
      concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood
      [HA] were elevated in Parkinson's disease (PD) as well. METHODS: Blood [HA] were
      quantified by high performance liquid chromatography. Subjects comprised 113 PD
      cases and 101 controls. RESULTS: Mean log blood [HA] in PD cases was double that
      of controls (0.59+/-0.63 g(-10)/ml vs. 0.27+/-0.63 g(-10)/ml, p<0.001). A non
      parametric test on non-transformed data (median blood [HA]=3.31 g(-10)/ml in
      cases and 1.44 g(-10)/ml in controls) also showed this difference (p<0.001). In
      unadjusted and then adjusted logistic regression analyses, log blood [HA] was
      associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI]
      1.46-3.67, p<0.001; OR(adjusted) 2.54, 95% CI 1.55-4.16, p<0.001). In PD, log
      blood [HA] co-varied with family history, being lowest in PD cases with no family
      history (0.54+/-0.60 g(-10)/ml) and highest in PD cases with a family history of
      both ET and PD (0.84+/-0.68 g(-10)/ml) (p=0.06). CONCLUSIONS: Blood harmane
      appears to be elevated in PD. The finding needs to be reproduced in additional
      cohorts to assess its generalizability. The higher concentration in familial PD
      suggests that the mechanism may involve genetic factors.

PMID- 24300780
TI  - Prognosis of proliferative lupus nephritis subsets in the Louvain Lupus Nephritis
      inception Cohort.
AB  - OBJECTIVE: The objective of this paper is to evaluate whether the different
      International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of
      proliferative lupus nephritis (LN) have a distinct baseline presentation, short
      term response to immunosuppression (IS) and long-term prognosis. METHODS: Ninety
      eight patients with new onset (first renal biopsy) ISN/RPS proliferative LN
      (Class III: n=24; IV-S: n=23; IV-G: n=51) were diagnosed at our institution
      between 1995 and 2012 (Louvain Lupus Nephritis inception Cohort). Their baseline
      renal parameters, primary response to IS at one year, survival and long-term
      renal outcome (mean follow-up: 77 months) were compared. RESULTS: At baseline,
      serum creatinine and 24-hour proteinuria were higher in Class IV-G, as was
      activity index on renal biopsy in Class IV-S and IV-G compared to III. Upon
      treatment, renal parameters improved with the same kinetics and to the same
      extent in the three pathological classes. On repeat renal biopsies (n=43),
      activity indices dropped similarly. Poor outcomes (death, end-stage renal
      disease, renal impairment defined by an eGFR <60 ml/min/1.73 m(2)) did not
      statistically differ between groups, although there was a trend toward more renal
      impairment at follow-up in Class IV-G compared to IV-S and III. Finally, the
      presence of even mild chronic lesions on baseline biopsy was clearly predictive
      of late renal outcome. CONCLUSION: Subsetting proliferative LN into Class III, IV
      S and IV-G provides less clinically discriminant prognostic information than
      baseline chronicity index.

PMID- 24300781
TI  - The association of anti-annexin1 antibodies with the occurrence of skin lesions
      in systemic lupus erythematosus.
AB  - Anti-annexin1 antibodies are associated with the subtypes of cutaneous lupus and
      are elevated in systemic lupus erythematosus (SLE) patients. In this study, we
      investigated the correlation of this antibody with the incidence of SLE skin
      lesions. The presence of anti-annexin1-IgG and-IgM determined by Western blot was
      no different among healthy controls and SLE patients with and without skin
      lesions. Serum levels of anti-annexin1-IgG and -IgM measured by enzyme-linked
      immunosorbent assay were comparable between patients with and without skin
      lesions, whereas anti-annexin1-IgM was lower in SLE patients than in healthy
      controls. Annexin1 was abundantly detected in each epidermal layer in lupus
      lesional skin. Additionally, anti-annexin1-IgG was higher in SLE patients with
      arthritis and negatively correlated with white blood cells (WBC). Anti-annexin1
      IgM was higher in patients with antinuclear antibody (ANA)-positive sera, and was
      positively related to hemoglobin and total serum IgM. Collectively, anti-annexin1
      antibodies are not related to the incidence of skin lesions in SLE, and annexin1
      abundantly distributes in epidermis in lesional skin. 

PMID- 24300782
TI  - Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double
      blind crossover pilot study.
AB  - In preclinical studies growth hormone and its primary mediator IGF-1 have shown
      potential to increase muscle mass and strength. A single patient with spinal
      muscular atrophy reported benefit after compassionate use of growth hormone.
      Therefore we evaluated the efficacy and safety of growth hormone treatment for
      spinal muscular atrophy in a multicenter, randomised, double-blind, placebo
      controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal
      muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or
      placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before
      3 months of treatment with the contrary remedy. Changes in upper limb muscle
      strength (megascore for elbow flexion and hand-grip in Newton) were assessed by
      hand-held myometry as the primary measure of outcome. Secondary outcome measures
      included lower limb muscle strength, motor function using the Hammersmith
      Functional Motor Scale and other functional tests for motor function and
      pulmonary function. Somatropin treatment did not significantly affect upper limb
      muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:
      3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N,
      CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects
      occurring during somatropin treatment corresponded with well-known side effects
      of growth hormone substitution in patients with growth hormone deficiency. In
      this pilot study, growth hormone treatment did not improve muscle strength or
      function in patients with spinal muscular atrophy type II/III.

PMID- 24300783
TI  - Exome sequencing identifies Laing distal myopathy MYH7 mutation in a Roma family
      previously diagnosed with distal neuronopathy.
AB  - We describe a Hungarian Roma family, originally investigated for autosomal
      dominant distal muscular atrophy. The mother started toe walking at 3 years and
      lost ambulation at age 27. Her three daughters presented with early steppage gait
      and showed variable progression. Muscle biopsies were nonspecific showing
      myogenic lesions in the mother and lesions resembling neurogenic atrophy in the
      two siblings. To identify the causative abnormality whole exome sequencing was
      performed in two affected girls and their unaffected father, unexpectedly
      revealing the MYH7 mutation c.4849_4851delAAG (p.K1617del) in both girls,
      reported to be causative for Laing distal myopathy. Sanger sequencing confirmed
      the mutation in the affected mother and third affected daughter. In line with
      variable severity in Laing distal myopathy our patients presented a more severe
      phenotype. Our case is the first demonstration of Laing distal myopathy in the
      Roma and the successful use of whole exome sequencing in obtaining a definitive
      diagnosis in ambiguous cases.

PMID- 24300784
TI  - Compound heterozygous mutations of the TNXB gene cause primary myopathy.

PMID- 24300785
TI  - Electrochemical detection of human papillomavirus DNA type 16 using a
      pyrrolidinyl peptide nucleic acid probe immobilized on screen-printed carbon
      electrodes.
AB  - An electrochemical biosensor based on an immobilized anthraquinone-labeled
      pyrrolidinyl peptide nucleic acid (acpcPNA) probe was successfully developed for
      the selective detection of human papillomavirus (HPV) type 16 DNA. A 14-mer
      acpcPNA capture probe was designed to recognize a specific 14 nucleotide region
      of HPV type 16 L1 gene. The redox-active label anthraquinone (AQ) was covalently
      attached to the N-terminus of the acpcPNA probe through an amide bond. The probe
      was immobilized onto a chitosan-modified disposable screen-printed carbon
      electrode via a C-terminal lysine residue using glutaraldehyde as a cross-linking
      agent. Hybridization with the target DNA was studied by measuring the
      electrochemical signal response of the AQ label using square-wave voltammetric
      analysis. The calibration curve exhibited a linear range between 0.02 and 12.0 uM
      with a limit of detection and limit of quantitation of 4 and 14 nM, respectively.
      This DNA sensing platform was successfully applied to detect the HPV type 16 DNA
      from a PCR amplified (240 bp fragment of the L1 gene) sample derived from the HPV
      type 16 positive human cancer cell line (SiHa), and failed to detect the HPV
      negative c33a cell line. The sensor probe exhibited very high selectivity for the
      complementary 14 base oligonucleotide over the non-complementary oligonucleotides
      with sequences derived from HPV types 18, 31 and 33. The proposed sensor provides
      an inexpensive tool for the early stage detection of HPV type 16, which is an
      important biomarker for cervical cancer.

PMID- 24300786
TI  - Enhanced cancer radiotherapy through immunosuppressive stromal cell destruction
      in tumors.
AB  - PURPOSE: Radiotherapy kills cancer cells by causing DNA damage, and stimulates a
      systemic antitumor immune response by releasing tumor antigen and endogenous
      adjuvant within the tumor microenvironment. However, radiotherapy also induces
      the recruitment of immunosuppressive myeloid cells, which can interfere with the
      antitumor immune responses elicited by apoptotic tumor cells. We hypothesized
      that local delivery of vaccine following radiotherapy will lead to the priming of
      antigen-specific CTL immune responses and render immunosuppressive myeloid cells
      susceptible to killing by the activated CTLs. EXPERIMENTAL DESIGN: Using several
      antigenic systems, we tested whether intratumoral injection of antigenic
      peptide/protein in irradiated tumors would be able to prime CTLs as well as load
      myeloid cells with antigen, rendering them susceptible to antigen-specific CTL
      killing. RESULTS: We show that by combining radiotherapy and targeted antigenic
      peptide delivery to the tumor, the adjuvant effect generated by radiotherapy
      itself was sufficient to elicit the priming and expansion of antigen-specific
      CTLs, through the type I IFN-dependent pathway, leading to synergistic
      therapeutic antitumor effects compared with either treatment alone. In addition,
      using two different types of transgenic mice, we demonstrated that CTL-mediated
      killing of stromal cells in tumors by our approach is important for tumor
      control. Finally, we confirmed the efficacy of this approach in our preclinical
      model using two clinically tested therapeutic human papilloma virus (HPV)
      vaccines. CONCLUSIONS: These data serve as an important foundation for the future
      clinical translation of radiotherapy combined with a clinically tested
      therapeutic HPV vaccine for the control of HPV-associated cancers.

PMID- 24300788
TI  - Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial
      in a pet dog model of diffuse large B-cell lymphoma.
AB  - PURPOSE: Active immunotherapy is a promising antitumoral strategy; however its
      use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL)
      remains largely untested. Heat shock proteins (HSP) bind the small peptides they
      chaperone (HSPPC), allowing for immunization of the host against a large
      repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts
      as an immunologic adjuvant. The aim of this study was to show that an autologous
      vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically
      effective in dogs with DLBCL. EXPERIMENTAL DESIGN: Nineteen dogs with naturally
      occurring DLBCL were entered into a prospective randomized placebo-controlled
      double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus
      chemotherapy alone. Endpoints included time to progression (TTP), lymphoma
      specific survival (LSS), and incidence of toxicoses. RESULTS: Median first TTP
      after randomization to the vaccine arm was 304 days versus 41 days for the
      control arm (P = 0.0004). There was also a statistically significant difference
      in duration of second remission between the two groups (P = 0.02). Median LSS was
      505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P =
      0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal
      immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two
      treatment arms. CONCLUSIONS: The results of this trial demonstrate that the
      autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS
      in dogs with DLBCL when used in combination with dose-intense chemotherapy. On
      the basis of these results, additional evaluation of this novel therapeutic
      strategy is warranted in human DLBCL.

PMID- 24300787
TI  - PID1 (NYGGF4), a new growth-inhibitory gene in embryonal brain tumors and
      gliomas.
AB  - PURPOSE: We present here the first report of PID1 (Phosphotyrosine Interaction
      Domain containing 1; NYGGF4) in cancer. PID1 was identified in 2006 as a gene
      that modulates insulin signaling and mitochondrial function in adipocytes and
      muscle cells. EXPERIMENTAL DESIGN AND RESULTS: Using four independent
      medulloblastoma datasets, we show that mean PID1 mRNA levels were lower in
      unfavorable medulloblastomas (groups 3 and 4, and anaplastic histology) compared
      with favorable medulloblastomas (SHH and WNT groups, and desmoplastic/nodular
      histology) and with fetal cerebellum. In two large independent glioma datasets,
      PID1 mRNA was lower in glioblastomas (GBM), the most malignant gliomas, compared
      with other astrocytomas, oligodendrogliomas and nontumor brains. Neural and
      proneural GBM subtypes had higher PID1 mRNA compared with classical and
      mesenchymal GBM. Importantly, overall survival and radiation-free progression
      free survival were longer in medulloblastoma patients whose tumors had higher
      PID1 mRNA (univariate and multivariate analyses). Higher PID1 mRNA also
      correlated with longer overall survival in patients with glioma and GBM. In cell
      culture, overexpression of PID1 inhibited colony formation in medulloblastoma,
      atypical teratoid rhabdoid tumor (ATRT), and GBM cell lines. Increasing PID1 also
      increased cell death and apoptosis, inhibited proliferation, induced
      mitochondrial depolaization, and decreased serum-mediated phosphorylation of AKT
      and ERK in medulloblastoma, ATRT, and/or GBM cell lines, whereas siRNA to PID1
      diminished mitochondrial depolarization. CONCLUSIONS: These data are the first to
      link PID1 to cancer and suggest that PID1 may have a tumor inhibitory function in
      these pediatric and adult brain tumors.

PMID- 24300789
TI  - Ocular motor disorders.
AB  - PURPOSE OF REVIEW: Studying eye movements can provide insight into how the normal
      brain works, how diseases affect eye movements, and how eye movement
      abnormalities can be used to study diseases and/or their treatments. In this
      review, we concentrate on recent studies looking at abnormalities of saccades in
      various diseases. RECENT FINDINGS: Various saccadic abnormalities have been found
      in Parkinson's disease, Huntington's disease, dementia, cerebellar disease,
      schizophrenia, and several other conditions. In some of these, saccadic
      abnormalities appear to be capable of distinguishing different subtypes (e.g.,
      progressive supranuclear palsy from idiopathic Parkinson's disease, Alzheimer's
      disease from frontotemporal dementia, or one type of spinocerebellar ataxia from
      another). Several studies have looked at functional associations of saccadic
      abnormalities (e.g., reading in spinocerebellar ataxia or recovery from stroke),
      which may prove clinically useful. Studies on microsaccades have revealed
      abnormalities in various diseases, and suggest that they may provide a useful
      marker of fatigue. SUMMARY: Saccadic eye movements provide an excellent way of
      studying the human motor system in health and disease, as well as providing
      insight into various aspects of cognitive function. Assessment of saccades in the
      laboratory and at the bedside is likely to become increasingly useful clinically.

PMID- 24300790
TI  - Pathophysiology and risk factors of cervical artery dissection: what have we
      learnt from large hospital-based cohorts?
AB  - PURPOSE OF REVIEW: Cervical artery dissection (CeAD) is a major cause of ischemic
      stroke in young and middle-aged adults, although relatively uncommon in the
      community. Recent large collaborative projects have provided new insights into
      mechanisms and risk factors of CeAD. RECENT FINDINGS: Pathologic changes observed
      at the media-adventitia border in temporal arteries of CeAD patients suggest a
      predisposing arterial wall weakness. In large multicenter series of CeAD
      patients, compared to age-matched healthy controls and patients with an ischemic
      stroke of another cause, hypertension and migraine, especially without aura, were
      confirmed as risk factors for CeAD, in addition to cervical trauma and recent
      infection. Hypercholesterolemia and being overweight were shown to be inversely
      associated with CeAD. Differences in risk factor profile and structural features
      between carotid and vertebral dissection suggest that their pathophysiology may
      partly differ. An association of CeAD with fibromuscular dysplasia and reversible
      cerebral vasoconstriction syndrome was described. Genetic risk factors of CeAD
      are still poorly understood. SUMMARY: Large cohorts of CeAD patients have refined
      our understanding of the pathophysiology and risk factors of CeAD, but the
      molecular mechanisms are still poorly understood. Ongoing high-throughput genetic
      projects will hopefully provide novel insight into the biological substrate of
      CeAD.

PMID- 24300792
TI  - Fear of heights and visual height intolerance.
AB  - PURPOSE OF REVIEW: The aim of this review is, first, to cover the different
      aspects of visual height intolerance such as historical descriptions, definition
      of terms, phenomenology of the condition, neurophysiological control of gaze,
      stance and locomotion, and therapy, and, second, to identify warranted
      epidemiological and experimental studies. RECENT FINDINGS: Vivid descriptions of
      fear of heights can be found in ancient texts from the Greek, Roman, and Chinese
      classics. The life-time prevalence of visual height intolerance is as high as 28%
      in the general population, and about 50% of those who are susceptible report an
      impact on quality of life. When exposed to heights, visual exploration by eye and
      head movements is restricted, and the velocity of locomotion is reduced. Therapy
      for fear of heights is dominated by the behavioral techniques applied during real
      or virtual reality exposure. Their efficacy might be facilitated by the
      administration of D-cycloserine or glucocorticoids. SUMMARY: Visual height
      intolerance has a considerable impact on daily life and interpersonal
      interactions. It is much more frequent than fear of heights, which is defined as
      an environmental subtype of a specific phobia. There is certainly a continuum
      stretching from acrophobia to a less-pronounced visual height intolerance, to
      which the categorical distinction of a specific phobia does not apply.

PMID- 24300791
TI  - Novel brain imaging approaches to understand acquired and congenital neuro
      ophthalmological conditions.
AB  - PURPOSE OF REVIEW: The arrival of large datasets and the on-going refinement of
      neuroimaging technology have led to a number of recent advances in our
      understanding of visual pathway disorders. This work can broadly be classified
      into two areas, both of which are important when considering the optimal
      management strategies. The first looks at the delineation of damage, teasing out
      subtle changes to (specific components of) the visual pathway, which may help
      evaluate the severity and extent of disease. The second uses neuroimaging to
      investigate neuroplasticity, via changes in connectivity, cortical thickness, and
      retinotopic maps within the visual cortex. RECENT FINDINGS: Here, we give
      consideration to both acquired and congenital patients with damage to the visual
      pathway, and how they differ. Congenital disorders of the peripheral visual
      system can provide insight into the large-scale reorganization of the visual
      cortex: these are investigated with reference to disorders of the optic chiasm
      and anophthalmia (absence of the eyes). In acquired conditions, we consider the
      recent work describing patterns of degeneration, both following single insult and
      in neurodegenerative conditions. We also discuss the developments in functional
      neuroimaging, with particular reference to work on hemianopia and the
      controversial suggestion of cortical reorganization following acquired retinal
      injury. SUMMARY: Techniques for comparing neuro-ophthalmological conditions with
      healthy visual systems provide sensitive metrics to uncover subtle differences in
      grey and white matter structure of the brain. It is now possible to compare the
      massive reorganization present in congenital conditions with the apparent lack of
      plasticity following acquired damage.

PMID- 24300793
TI  - Closure of patent foramen ovale in cryptogenic stroke: a never ending story.
AB  - PURPOSE OF REVIEW: This review discusses current evidence on patent foramen ovale
      (PFO) closure compared with medical therapy alone in the prevention of stroke
      recurrence in patients with a PFO-associated cryptogenic stroke. RECENT FINDINGS:
      The Risk of Paradoxical Embolism group built a 10-point Score, based on clinical
      parameters, that estimates the probability of finding a PFO in a patient with
      cryptogenic stroke and the probability that a PFO discovered in the setting of
      cryptogenic stroke is related to stroke vs. incidental.Three recent randomized
      clinical trials failed to demonstrate the superiority of PFO closure over medical
      treatment alone in preventing stroke recurrence in patients aged 18-60 years who
      have had a cryptogenic stroke or transient ischemic attack. SUMMARY: Stronger
      evidence in favor of PFO closure is needed before recommending this procedure
      outside of a clinical trial. Results of ongoing trials are much awaited.

PMID- 24300794
TI  - Arterial spin labeling magnetic resonance perfusion imaging in cerebral ischemia.
AB  - PURPOSE OF REVIEW: Arterial spin labeling (ASL) is a noninvasive magnetic
      resonance perfusion imaging method for visualizing and quantifying whole-brain
      perfusion that does not require exogenous contrast agents. The goal of this
      review article is to explain the principles of ASL perfusion imaging and review
      the strengths and limitations of different ASL methods. RECENT FINDINGS: There
      are several different approaches that vary mainly on the basis of the technique
      that is used to label the inflowing arterial blood. These methods can be used to
      assess perfusion at brain tissue level or the perfusion territories of the brain
      feeding arteries. In patients with acute ischemic stroke, ASL can be of clinical
      value by detecting brain regions with hypoperfusion and perfusion-diffusion
      mismatch. ASL has been used to detect decreased perfusion, delayed arrival of the
      arterial blood bolus and assessment of collateral blood flow in patients with
      extracranial large artery disease and moyamoya disease. SUMMARY: Recent evidence
      indicates that perfusion and territorial perfusion imaging of the brain feeding
      arteries with ASL can help to assess the extent of hemodynamic compromise and to
      customize medicinal and surgical treatment, both in patients with acute and with
      chronic cerebrovascular disease.

PMID- 24300795
TI  - Are we overestimating the stroke risk related to contraceptive pills?
AB  - PURPOSE OF REVIEW: Hormonal contraceptives are used by million of women
      worldwide. Ischemic stroke is one of the major harmful effects of hormonal
      contraceptives, but remains a very uncommon disease before menopause. The
      increased risk of stroke under third and fourth-generation contraceptive pills
      and nonoral contraceptives has been recently highlighted. Given the benefits
      associated with combined hormonal contraceptives (COCs), it is important to
      properly evaluate their risks in order to provide a better benefit/risk balance
      to young women. RECENT FINDINGS: Scarce studies addressing the rates of stroke in
      young women suggest that the fraction attributable to the contraceptive pill
      remains low. In contrast, there is abundant literature on the relative risks of
      stroke under COCs. The risk of arterial disease seems to be similar among users
      of second and third-generation pills, drospirenone-containing pills and nonoral
      hormonal contraceptives. Progestin-only contraceptives do not appear to be
      associated with an increased risk of stroke. SUMMARY: New formulations of
      hormonal contraceptives are not safer than second-generation COCs. Even if the
      absolute numbers of strokes attributable to hormonal contraceptives is very low,
      stringent selection of patients should help to reduce the events still more, and
      progestin-only contraceptives/nonhormonal methods should be preferred in cases of
      associated risk factors.

PMID- 24300796
TI  - Microinjection wound assay and in vivo localization of epidermal wound response
      reporters in Drosophila embryos.
AB  - The Drosophila embryo develops a robust epidermal layer that serves both to
      protect the internal cells from a harsh external environment as well as to
      maintain cellular homeostasis. Puncture injury with glass needles provides a
      direct method to trigger a rapid epidermal wound response that activates wound
      transcriptional reporters, which can be visualized by a localized reporter signal
      in living embryos or larvae. Puncture or laser injury also provides signals that
      promote the recruitment of hemocytes to the wound site. Surprisingly, severe
      (through and through) puncture injury in late stage embryos only rarely disrupts
      normal embryonic development, as greater than 90% of such wounded embryos survive
      to adulthood when embryos are injected in an oil medium that minimizes immediate
      leakage of hemolymph from puncture sites. The wound procedure does require
      micromanipulation of the Drosophila embryos, including manual alignment of the
      embryos on agar plates and transfer of the aligned embryos to microscope slides.
      The Drosophila epidermal wound response assay provides a quick system to test the
      genetic requirements of a variety of biological functions that promote wound
      healing, as well as a way to screen for potential chemical compounds that promote
      wound healing. The short life cycle and easy culturing routine make Drosophila a
      powerful model organism. Drosophila clean wound healing appears to coordinate the
      epidermal regenerative response, with the innate immune response, in ways that
      are still under investigation, which provides an excellent system to find
      conserved regulatory mechanisms common to Drosophila and mammalian epidermal
      wounding. 

PMID- 24300797
TI  - Quantitative assessment of human neutrophil migration across a cultured bladder
      epithelium.
AB  - The recruitment of immune cells from the periphery to the site of inflammation is
      an essential step in the innate immune response at any mucosal surface. During
      infection of the urinary bladder, polymorphonuclear leukocytes (PMN; neutrophils)
      migrate from the bloodstream and traverse the bladder epithelium. Failure to
      resolve infection in the absence of a neutrophilic response demonstrates the
      importance of PMN in bladder defense. To facilitate colonization of the bladder
      epithelium, uropathogenic Escherichia coli (UPEC), the causative agent of the
      majority of urinary tract infections (UTIs), dampen the acute inflammatory
      response using a variety of partially defined mechanisms. To further investigate
      the interplay between host and bacterial pathogen, we developed an in vitro model
      of this aspect of the innate immune response to UPEC. In the transuroepithelial
      neutrophil migration assay, a variation on the Boyden chamber, cultured bladder
      epithelial cells are grown to confluence on the underside of a permeable support.
      PMN are isolated from human venous blood and are applied to the basolateral side
      of the bladder epithelial cell layers. PMN migration representing the
      physiologically relevant basolateral-to-apical direction in response to bacterial
      infection or chemoattractant molecules is enumerated using a hemocytometer. This
      model can be used to investigate interactions between UPEC and eukaryotic cells
      as well as to interrogate the molecular requirements for the traversal of bladder
      epithelia by PMN. The transuroepithelial neutrophil migration model will further
      our understanding of the initial inflammatory response to UPEC in the bladder. 

PMID- 24300798
TI  - [Actual problems of inpatient psychiatric care in Russia].
AB  - A comparative evaluation of inpatient psychiatric care in Russia and some other
      countries is presented. A systematic analysis of the performance of psychiatric
      hospitals is conducted. The process of the deinstitutionalization in Russian
      psychiatry is highlighted. A range of problems hindering a reform of inpatient
      psychiatric service of the country is singled out. 

PMID- 24300799
TI  - [Neuropsychological features of mixed Alzheimer's and vascular dementia].
AB  - Neuropsychological syndrome was defined in 94 patients with mixed
      Alzheimer's/vascular dementia, 75 patients with vascular dementia and 114
      patients with Alzheimer's disease (AD) without clinical signs of cerebrovascular
      disease. Based on this data, the authors singled out main components of
      neuropsychological disorders in mild and moderate mixed dementia. The comparison
      of results of the quantitative assessment of neuropsychological functions (total
      parameters of three blocks of the brain according to A.R. Luria) in mixed
      dementia and AD revealed significant between-group differences at the stage of
      mild dementia. No differences was found between AD and moderate dementia. It has
      been concluded that the assessment of neuropsychological functions should be used
      for differential diagnosis of different forms of late-onset dementia and may help
      in understanding of the contribution of risk vascular factors to the development
      of dementia.

PMID- 24300800
TI  - [Premorbid border-line mental disorders in adolescents and young-aged people].
AB  - The aim of the study was to determine the predictive value of some types of
      premorbid state for the development of border-line mental diseases (neurotic
      disorders and personality disorders). We examined 579 school students and 523
      university students. The study comprised two stages: primary examination and
      follow-up (2 years). Some forms of premorbid mental disorders and their impact on
      the development of border-line mental diseases were described. The predictive
      value of different premorbid disorders was estimated. 

PMID- 24300801
TI  - [Attitude to disease and psychotherapeutic strategies in youths with the first
      psychotic episode].
AB  - To study attitude to disease in patients with the first episode of juvenile
      endogenous psychosis (ICD-10 items F20, F25, F30.21 and F32.3), authors examined
      89 male patients. There were common patterns in attitude to disease caused by the
      pathoplastic effect of juvenile age and some differences that were correlated
      with premorbid personality features and the psychopathological structure of the
      psychotic episode. Normonosognosic, hyponosognosic, hypernosognosic and
      disnosognosic types of attitude to disease were singled out. Hyponosognosic type
      was the most common in patients with the first episode of juvenile endogenous
      psychosis. Its were elaborated recommendations for differential use of
      psychotherapeutic strategies which took into account attitude to disease and age
      of the patient. 

PMID- 24300802
TI  - [The functional asymmetry of the facial neuromotor apparatus in patients with
      facial nerve neuropathy and its treatment with botulinum toxin type A lantox].
AB  - A clinical and electrophysiological (EMG, ENMG, the blink reflex) examination has
      been carried out in 85 patients with facial nerve lesions of different etiology.
      A control group included 25 healthy people. Two schemes of botulinum toxin type A
      (lantox) injections into hyperactive facial muscles have been elaborated. The
      second examination has been conducted 14 days after injections. The compensatory
      tug of paretic muscles accompanied by the hypertonic activity of facial muscles
      of an intact side has been observed in patients with facial nerve neuropathy. The
      results of the study have been analyzed in 64 patients stratified into two
      subgroups: 29 patients with prosopoplegia and 35 patients with late
      complications. After the treatment, the tone of facial muscles has decreased thus
      promoting the balance between facial muscles on both sides of the face, decrease
      in facial asymmetry, increase of the functional muscle interaction between both
      sides, reduction of pathological synkinetic activity. The authors emphasize that
      the use of botulinum toxin type A both in the early and recovery stages allows to
      obtain high functional and esthetic results. 

PMID- 24300804
TI  - [Morphometric parameters of the neurodegenerative process in Parkinson's disease
      and chronic cerebral ischemia].
AB  - Authors have compared the results of MRI volumetric morphometry of brain
      hemispheres, substantia nigra and red nucleus in patients with different stages
      of Parkinson's disease (PD), patients with early and developed stages of
      cerebrovascular disease and healthy people. Already in the early stage of
      disease, the degree of cerebral hemisphere atrophy was more pronounced in
      patients with cerebrovascular disease compared to PD patients. At the same time,
      multidirectional changes in the size of the substantia nigra were noted. This
      finding may be relevant for the diagnosis of PD in the early stages. 

PMID- 24300803
TI  - [Cognitive disorders and their correction in patients with ischemic stroke].
AB  - A study of the effectiveness of long-term (within a year) use cytoprotector
      neuropeptide nature of the drug cortexin (in the acute, early and late recovery
      periods) on the dynamics of the cognitive status of patients with ischemic
      stroke. The study involved 80 patients first ischemic stroke (IS). The patients
      of the main group (40 patients) received standard therapy cortexin + 10 mg once a
      day intramuscularly for 10 days with the same course again at 3, 6, 9 months
      during the year, the control group (40 people) - basic and vascular therapy for
      year. Four-time reception cortexin for a year at 10 mg once a day for 10 days
      promotes regression pronounced movement disorders, stabilize and restore
      cognitive function, and minimize the likelihood of post-stroke cognitive
      impairment during the recovery period. 

PMID- 24300805
TI  - [Pharmacotherapy of endothelial dysfunction in patients with atherosclerotic
      brain ischemia].
AB  - We studied the effect of deproteinized hemoderivative of calf blood, thioctic
      acid and vinpocetine with piracetam on the endothelial function in patients with
      chronic cerebral ischemia stage III. After pharmacological treatment, there was
      the improvement in the endothelium properties of both large and small blood
      vessels. The index of occlusion that characterized the function of small vessels
      reached normal values while the phase shift did not approach to the reference
      values. This notion indicates that in cerebral atherosclerosis small arteries
      initially are subject to alterations to a lesser extent compared to the arteries
      of large and medium caliber. The most effective medicines of those used for the
      correction of endothelial dysfunction are deproteinized hemoderivative of calf
      blood and thioctic acid. 

PMID- 24300806
TI  - [Interaction effects of anxiety and the BDNF Val66Met polymorphism on attention
      in patients with schizophrenia spectrum disorders].
AB  - Authors investigated effects of the Val66Met polymorphism of the brain-derived
      neurotrophic factor (BDNF) gene and level of trait anxiety on attention in 90
      patients with schizophrenia or schizoaffective psychosis. Attention was assessed
      using auditory event-related brain potentials (ERPs) and neuropsychological
      testing. There was a significant effect of the BDNF genotype, but not anxiety, on
      performance on the neuropsychological test and on the P300 amplitude in frontal
      and temporal leads. Carriers of a Met allele performed worse and showed lower
      P300 amplitude during the attention task than those with the ValVal genotype. The
      interaction effect of the genotype and anxiety was observed for non-target N100
      amplitude in central and parietal leads. This effect depended on the level of
      anxiety: the interaction was significant only in the group with the lower level
      of anxiety. In this group, a Met allele was associated with the lower N100
      amplitude. It was suggested that BDNF genotype does not contribute to brain
      electrical activity at the first stage of stimulus recognition (N100) because
      highly anxious people tend to be more attentive, regardless of genotype, due to
      the fear about their ability to cope with the task requirements. 

PMID- 24300807
TI  - [Clinical and electrophysiological and molecular genetic characteristics of the
      course of relapsing-remitting multiple sclerosis].
AB  - In order to study specific features of remitting multiple sclerosis patients with
      different genotypes of polymorphic loci rs1800629 gene TNFalpha, rs6074022 gene
      CD40, rs10492972 gene KIF1B, rs187238 IL-18 gene, conducted clinical and
      electrophysiological examination of 149 patients with relapsing-remitting
      multiple sclerosis. Found that the most common symptoms of rapidly progressive
      relapsing-remitting multiple sclerosis were cerebellar and sensory disorders.
      Severity of pyramidal and cerebellar, stem, pelvic disorders, and thus the value
      of EDSS score was significantly higher in the group of patients with recurrent
      exacerbations during the year. Intensity changes of latencies of peaks I, III of
      short-stem evoked potentials and central motor conduction time determined by the
      ball on a scale EDSS. Genotype C/C polymorphism rs187238 locus IL-18 gene
      associated with frequent exacerbations of relapsing-remitting multiple sclerosis,
      high speed of progression of the disease and is characterized by marked changes
      in latency of peak V ABR and VEP P100. With polymorphic locus allele rs187238 IL
      18 is associated with more frequent exacerbations PPC (OR=1.714 (1.051-2.797);
      p=0.02), and increases the risk of rapidly progressive nature of the disease in a
      2-fold (OR=2.040 (1.140-3.650) p=0.015). 

PMID- 24300808
TI  - [Somatic comorbidity in epilepsy and its effect on disease course].

PMID- 24300809
TI  - [Subchromosomal microdeletion identified by molecular karyotyping using DNA
      microarrays (array CGH) in Rett syndrome girls negative for MECP2 gene
      mutations].
AB  - Molecular karyotyping using DNA microarrays (array CGH) was applied for
      identification of subchromosomal microdeletions in a cohort of 12 girls with
      clinical features of RETT syndrome, but negative for MECP2 gene mutations.
      Recurrent microdeletions of MECP2 gene in chromosome X (locus Xq28) were
      identified in 5 girls of 12 studied. Probably RTT girls with subchromosomic
      microdeletions in Xq28 could represent a special subtype of the disease, which
      appears as clinically milder than the classic form of disease. In one case, an
      atypical form of RTT was associated with genomic abnormalities affecting CDKL5
      gene and region critical for microdeletion Prader-Willi and Angelman syndromes
      (15q11.2). In addition, data are presented for the first time that genetic
      variation in regions 3p13, 3q27.1, and 1q21.1-1q21.2 could associate with RTT
      like clinical manifestations. Without application of molecular karyotyping
      technology and bioinformatic method of assessing the pathogenic significance of
      genomic rearrangements these RTT-like girls negative for MECP2 gene mutations
      were considered as cases of idiopathic mental retardation associated with autism.
      It should be noted that absence of intragenic mutations in MECP2 gene is not
      sufficient criteria to reject the clinical diagnosis of RTT. To avoid errors in
      the genetic diagnosis of this genetically heterogeneous brain disease molecular
      cytogenetic studies using high resolution oligonucleotide array CGH (molecular
      karyotyping) are needed. 

PMID- 24300810
TI  - [Kinesitherapy is a basic element of non-pharmacological treatment of Parkinson's
      disease].

PMID- 24300811
TI  - [Epidemiological characteristics of multiple sclerosis in the Kabardino-Balkaria
      Republic].
AB  - Prevalence of multiple sclerosis (MS) in two populations of the Kabardino
      Balkaria Republic (Nalchik and Prokhladnensky region) was studied. In Nalchik,
      the prevalence of MS was 13.0 cases per 100 000 in 2006 and 13.7 cases - in 2010.
      It was lower among Circassians (8.0) compared to Slavs (31.3). The 5-year
      morbidity was low (0.15 per 100 000 population). In 2010, the prevalence of MS in
      Nalchik was 34.3 per 100 000. In the rural Prokhladnensky region with mainly Slav
      population, the prevalence was 11.0 cases per 100 000 in 2006 and 19.8 (all
      patients were Slavs) - in 2010. The morbidity was 1.76 for the period analyzed.
      At the same time, the prevalence of MS in the Slav population in 2010 was lower
      by a factor of 1.73 in the rural region compared to Nalchik (19.8 and 34.3,
      respectively). The higher prevalence of MS in Nalchik may be explained by adverse
      environmental factors increasing the risk of MS. A case-control study revealed
      the higher risk for people under 15 years old living very close to chemical and
      biological plants. 

PMID- 24300812
TI  - [Clinical epidemiology of multiple sclerosis in Moscow. Descriptive epidemiology
      in population of one region of Moscow].
AB  - The epidemiological study of multiple sclerosis (MS) has been done in the
      population (927 400 people) of the North-Western Administrative District (SZAO)
      of Moscow for the period of 2008-2012. In average for the 5 years the prevalence
      of MS was amounted to 53.38 cases per 100 000 population, incidence was 2.16
      cases per 100 000 population and the mortality rate was 0.23 cases per 100 000
      population. Thus, the population of SZAO belongs to high-incidence area. An
      increase in the prevalence of MS as well as a reduction of incidence and
      mortality were observed during a comparative analysis with the epidemiological
      indicators of MS in Moscow in the period of 1991-1996. Such dynamics of
      epidemiological indicators is due to the accumulation of patients in population
      that, in the first place, is related with the quality improvement of diagnostic
      and therapeutic-rehabilitative measures which increased the frequency of early
      diagnosis and patient's life expectancy together with the implementation of
      disease-modifying therapy (DMT) and modern methods of symptomatic treatment. 

PMID- 24300813
TI  - [Clinical characteristics of multiple sclerosis in the Tomsk region].
AB  - To study clinical characteristics of multiple sclerosis (MS), we examined 280
      patients with different course of disease. There was the higher proportion of
      patients with remitting MS compared to patients with primarily-progressive
      course. The average severity of neurologic disability and average rate of
      progression of the disease were observed in most patients. The more favorable
      course of disease (the lesser severity of disability and slower rate of MS
      progression) was found in women. 

PMID- 24300814
TI  - [Relationship between biochemical parameters of cerebrospinal fluid and the
      course of multiple sclerosis].
AB  - We examined 60 patients with remitting multiple sclerosis (disability 3,5+/-1.6
      EDSS scores). The relative risk of rapid progression of neurologic impairment was
      associated with the higher levels of matrix metalloproteinase-2, soluble platelet
      endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell
      adhesion molecule-1 (sVCAM-1) in the cerebrospinal fluid. The relative risk of
      exacerbation of the disease in the next three years was associated with the level
      of tumor necrosis factor alpha and matrix metalloproteinase-2. 

PMID- 24300815
TI  - [The CD100 semaphorin expression on peripheral blood T-lymphocytes in patients
      with relapsing-remitting multiple sclerosis].
AB  - The expression of CD100 semaphorin by the intact peripheral blood T lymphocytes
      in multiple sclerosis (MS) has been studied. The level of middle florescence
      intensity (MFI) and the number of B-lymphocytes bearing CD72 were evaluated.
      There were significant differences in the level of CD100 in patients compared to
      healthy volunteers. These data suggest the use of semaphorin as a possible
      therapeutic target in pathological inflammation in MS. 

PMID- 24300816
TI  - [Pregnancy and delivery in women with multiple sclerosis: a retrospective
      analysis].
AB  - We have analyzed the course of multiple sclerosis (MS) in 155 pregnant women. In
      85.7% cases, pregnancy resulted in delivery and in 14.3% cases - in abortion.
      Patients presented with relapse very shortly after the abortion and received
      hormonal treatment. Patients treated with disease-modifying drugs (DMD) did not
      have relapses during pregnancy compared to those who did not receive DMD before
      the pregnancy. In the latter group, 33 (40.2%) patients presented with relapses
      during the I trimester. After the delivery, the relapses were noted in 31 (27.2%)
      patients during the first year. The maximal number of relapses was recorded to
      the 3rd month after the delivery (58.1%) with the gradual reduction to the end of
      the year (6th month - 29% and 12th month - 12.9%). Patients who did not receive
      DMD had more relapses to the 3rd and 6th months after delivery. In conclusion,
      the use of DMD before the pregnancy is an important factor for prevention of
      relapses during pregnancy and after delivery. 

PMID- 24300817
TI  - [Prognostic factors of multiple sclerosis in children and adolescents after the
      first demyelinating event].

PMID- 24300818
TI  - [Differential diagnosis of multiple sclerosis with pediatric onset: the
      experience of the Moscow Division for treatment of children and adolescents with
      multiple sclerosis].
AB  - The diagnosis of multiple sclerosis in children and adolescence should be
      differentiated from a group of rare white matter diseases, with fuzzy diagnostic
      criteria. Some of these conditions require modern diagnostic techniques and wide
      knowledge of the doctor. The Moscow Division for treatment of children and
      adolescents with multiple sclerosis is a specialized advisory structure, which
      has specialists with experience in the differential diagnosis of multiple
      sclerosis with pediatric onset. The emphasis on the clinical aspects in
      differential diagnosis of early onset multiple sclerosis can reduce the time for
      the diagnosis and help to avoid diagnostic mistakes.

PMID- 24300819
TI  - [Local reactions to disease-modifying drugs: pathogenesis and relationship to
      clinical effectiveness].
AB  - One of the most common adverse events of disease-modifying drugs in multiple
      sclerosis are local adverse reactions including redness and swelling at the
      injection site, compaction, panniculitis, lipoatrophy and others. This article
      provides an overview of the existing publications on the prevalence, pathogenesis
      and pathomorphology as well as data on the prevalence and characteristics of
      local reactions during DMD therapy of 193 patients. Authors defined a safety
      profile for local adverse reactions to interferon-Beta and glatiramer acetate and
      traced the relationship of lipoatrophy and pannikulita with effectiveness of
      therapy. 

PMID- 24300820
TI  - [Quality of life of patients receiving long-term treatment with first-line
      disease-modifying drugs: results of a Russian multicenter study using MusiQoL].
AB  - Results of a multicenter study of health-related quality of life (QoL) measured
      with the MusiQoL in 534 patients with multiple sclerosis (MS) treated with
      glatimer acetate (GA) given in subcutaneous injections in dosage 20 mg daily
      during at least 12 months are presented. The data were compared to those of the
      multicenter study of 1420 patients treated with interferon-Beta (44 mg three
      times a week). The influence of sex, age and MS duration on QoL was found. There
      was a significant improvement of QoL after 12 months of treatment with glatimer
      acetate. Positive changes in some MusiQoL domains were observed in patients
      treated with interferon-Beta after 6 months. 

PMID- 24300821
TI  - [The first experience of the use the Russian Beta-interferon-1b biosimilar
      (infibeta) in the daily practice of the Moscow Center of Multiple Sclerosis].
AB  - We summarized the 1-year experience of using the Russian Beta-interferon-1b
      biosimilar (infibeta) in 123 patients including 65 patients with relapsing
      remitting multiple sclerosis (RMS) and 58 patients with secondary progressive
      multiple sclerosis (SPMS). The significant decrease in the frequency of
      exacerbations per year was seen during the first year of treatment. We also noted
      the stabilization of the process of disability without the rise in EDSS scores in
      more than 50% of patients. Good tolerability comparable to that of the original
      drug was observed during the first year of treatment. There was no refusal from
      therapy with infibeta, which indicated sufficiently strong adherence to this type
      of treatment. 

PMID- 24300822
TI  - [Brain metabolism in multiple sclerosis: effects of neurotrophic therapy].
AB  - We studied 15 patients with relapsing-remitting multiple sclerosis (MS) in the
      state of remission (disease duration 1-5 years, EDSS scores 2.5-5.5) treated with
      serebrolysin (Cere) to investigate the rate of brain metabolism changes. All
      patients continued to receive their disease modified treatment therapy (copaxon
      or interferons). Patients of the main group (n=10) received i.v. 20 ml of Cere
      (diluted in 200 ml NaCl 0.9%) for 10 days and vitamins B (pentovit) in tablets.
      Patients in the control group (n=5) were treated only with pentovit in tablets.
      All the patients underwent magnetic resonance spectroscopy (MRS) (Siemens
      Symphony 1.5T) prior to the beginning of treatment and 1-3 days after the end of
      therapy. Five patients of the main group who had best results according to the
      data obtained from the 2nd MRS underwent a third MRS investigation after 3
      months. After 10 days of Cere treatment, the level of N-acetylaspartate in MS
      lesions had increased from 2.12 to 2.39 (p<0.001) and the level of lactate had
      decreased by 4 times (from 0.21 to 0.05; p<0.001). In perifocal lesion areas, the
      level of lactate had significantly decreased from 0.22 to 0.1 (p<0.05). We have
      also found the trend towards NAA increase in morphologically intact brain
      tissues. The positive metabolic changes after Cere therapy remained in some
      patients for 3 months. In the control group, there was the increase of creatine
      level in intact brain tissues from 1.16 to 1.30 (p<0.05) without significant
      changes in other areas. All the patients in the main group reported subjective
      improvement and one patient had the improvement in EDSS scores by 1.0 point. 

PMID- 24300823
TI  - Noninvasive intratracheal intubation to study the pathology and physiology of
      mouse lung.
AB  - The use of a model that mimics the condition of lung diseases in humans is
      critical for studying the pathophysiology and/or etiology of a particular disease
      and for developing therapeutic intervention. With the increasing availability of
      knockout and transgenic derivatives, together with a vast amount of genetic
      information, mice provide one of the best models to study the molecular
      mechanisms underlying the pathology and physiology of lung diseases. Inhalation,
      intranasal instillation, intratracheal instillation, and intratracheal intubation
      are the most widely used techniques by a number of investigators to administer
      materials of interest to mouse lungs. There are pros and cons for each technique
      depending on the goals of a study. Here a noninvasive intratracheal intubation
      method that can directly deliver exogenous materials to mouse lungs is presented.
      This technique was applied to administer bleomycin to mouse lungs as a model to
      study pulmonary fibrosis. 

PMID- 24300824
TI  - All-trans retinoic acid modulates bone morphogenic protein 9-induced osteogenesis
      and adipogenesis of preadipocytes through BMP/Smad and Wnt/beta-catenin signaling
      pathways.
AB  - It is known that excessive adipogenesis contributes to osteoporosis, suggesting
      that trans-differentiation of adipogenic committed preadipocytes into osteoblasts
      may be a potential therapeutical approach for osteoporosis. We explored whether
      bone morphogenic protein 9 (BMP9) could induce 3T3-L1 preadipocytes to trans
      differentiate into osteoblasts. BMP9 effectively increased expression of
      osteogenic markers and promoted mineralization in preadipocytes. However, BMP9
      also led to adipogenic differentiation of preadipocytes, as evidenced by
      increased lipid accumulation and up-regulation of adipogenic transcription
      factors. In order to regulate the switch between osetogenesis and adipogenesis,
      we evaluated the effect of all-trans retinoic acid (ATRA) on BMP9-induced
      differentiation of preadipocytes. We found that ATRA enhanced BMP9-induced
      osteogenic differentiation and blocked BMP9-induced adipogenic differentiation
      both in vitro and in vivo. Mechanistically, ATRA was shown to elevate BMP9
      expression and activate BMP/Smad signaling. Additionally, BMP9 and ATRA exerted a
      synergistic effect on activation of Wnt/beta-catenin signaling. Knockdown of beta
      catenin abolished the stimulatory effect of ATRA on BMP9-induced alkaline
      phosphatase activity and reversed the inhibitory effect of ATRA on BMP9-induced
      adipogenesis in preadipocytes. Furthermore, ATRA and BMP9 synergistically
      repressed glycogen synthase kinase 3beta (GSK3beta) activity and promoted Akt
      phosphorylation, and inhibited expression of phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) that antagonizes phosphatidylinositol-3-kinase
      (PI3K) function, suggesting that Wnt/beta-catenin signaling was activated at
      least partly through PI3K/Akt/GSK3beta pathway. Collectively, ATRA mediated BMP9
      induced osteogenic or adipogenic differentiation of 3T3-L1 preadipocytes by
      BMP/Smad and Wnt/beta-catenin signaling. The combination of BMP9 and ATRA may be
      explored as an effective therapeutic strategy for osteoporosis. 

PMID- 24300825
TI  - The malabsorption of commonly occurring mono and disaccharides: levels of
      investigation and differential diagnoses.
AB  - BACKGROUND: Adverse food reactions (AFR) have has recently attracted increased
      attention from the media and are now more commonly reported by patients. Its
      classification, diagnostic evaluation, and treatment are complex and present a
      considerable challenge in clinical practice. Non-immune-mediated types of food
      intolerance have a cumulative prevalence of 30% to 40%, while true (immune
      mediated) food allergies affect only 2% to 5% of the German population. METHOD:
      We selectively searched the literature for pertinent publications on carbohydrate
      malabsorption, with special attention to published guidelines and position
      papers. RESULTS: Carbohydrate intolerance can be the result of a rare, systemic
      metabolic defect (e.g., fructose intolerance, with a prevalence of 1 in 25,000
      persons) or of gastrointestinal carbohydrate malabsorption. The malabsorption of
      simple carbohydrates is the most common type of non-immune-mediated food
      intolerance, affecting 20% to 30% of the European population. This condition is
      caused either by deficient digestion of lactose or by malabsorption of fructose
      and/or sorbitol. Half of all cases of gastrointestinal carbohydrate intolerance
      have nonspecific manifestations, with a differential diagnosis including
      irritable bowel syndrome, intolerance reactions, chronic infections, bacterial
      overgrowth, drug side effects, and other diseases. The diagnostic evaluation
      includes a nutritional history, an H2 breath test, ultrasonography, endoscopy,
      and stool culture. CONCLUSION: The goals of treatment for carbohydrate
      malabsorption are to eliminate the intake of the responsible carbohydrate
      substance or reduce it to a tolerable amount and to assure the physiological
      nutritional composition of the patient's diet. In parallel with these goals, the
      patient should receive extensive information about the condition, and any
      underlying disease should be adequately treated.

PMID- 24300827
TI  - Genetic and familial environmental effects on suicide attempts: a study of Danish
      adoptees and their biological and adoptive siblings.
AB  - OBJECTIVES: Genetic factors have been found to influence the risk of suicide. It
      is less clear if this also applies to attempted suicide. We have investigated
      genetic and familial environmental factors by studying the occurrence of suicide
      attempts in biological and adoptive siblings of adoptees who attempted suicide
      compared to siblings of adoptees with no suicide attempts. METHOD: We used a
      random sample of 1933 adoptees from the Danish Adoption Register, a register of
      non-familial adoptions of Danish children, i.e. the adoptive parents are
      biologically unrelated to the adoptee. Analyses were conducted on incidence rates
      of attempted suicide in biological and adoptive siblings given occurrence of
      attempted suicide in the adoptees while also taking into account psychiatric
      disorders. Information about suicidal attempt and history of psychiatric disorder
      was based on hospital admissions. RESULTS: The rate of attempted suicide in full
      siblings of adoptees who attempted suicide before age 60 years was higher than in
      full siblings of adoptees who had not attempted suicide (incidence rate ratios
      (IRR)=3.45; 95% confidence interval [CI]=0.94-12.7). After adjustment for history
      of psychiatric admission of siblings the increased rate was statistically
      significant (IRR=3.88; 95% CI-1.42-10.6). LIMITATIONS: Information on attempted
      suicide and psychiatric history was limited to that which involved
      hospitalisation. CONCLUSIONS: Genetic factors influence risk of suicide attempts.

PMID- 24300826
TI  - Myelodysplastic syndromes: diagnosis, prognosis, and treatment.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) are malignant stem-cell diseases that
      are usually diagnosed in elderly patients who present with anemia or, less
      commonly, bi- or pancytopenia. Their incidence in persons over age 80 is above 50
      new cases per 100,000 persons per year. Their clinical course is highly variable.
      About one-quarter of all patients with MDS develop acute leukemia. The median
      survival time from the moment of diagnosis is about 30 months. METHOD: We
      selectively searched the PubMed database for pertinent articles and guidelines
      from the years 2000-2013. We used the search term "myelodysplastic syndromes."
      RESULTS: MDS are diagnosed by cytology, with consideration of the degree of
      dysplasia and the percentage of blast cells in the blood and bone marrow, and on
      a cytogenetic basis, as recommended in the WHO classification. In particular,
      chromosomal analysis is necessary for prognostication. The Revised International
      Prognosis Scoring System (IPSS-R) enables more accurate prediction of the course
      of disease by dividing patients into a number of low- and high-risk groups. The
      median survival time ranges from a few months to many years. The approved
      treatments, aside from transfusion therapy, include iron depletion therapy for
      low-risk patients, lenalidomide for low-risk patients with a deletion on the long
      arm of chromosome 5, and 5-azacytidine for high-risk patients. High-risk patients
      up to age 70 who have no major accompanying illnesses should be offered allogenic
      stem-cell transplantation with curative intent. The cure rates range from 30% to
      50%. Mucositis, hemorrhages, infections, and graft-versus-host diseases are the
      most common complications of this form of treatment. CONCLUSION: Myelodysplastic
      syndromes are treated on an individualized, risk-adapted basis after precise
      diagnostic evaluation and after assessment of the prognosis. More studies are
      needed so that stage-adapted treatment can be improved still further.

PMID- 24300828
TI  - Uncoupling of peripheral and master clock gene rhythms by reversed feeding leads
      to an exacerbated inflammatory response after polymicrobial sepsis in mice.
AB  - Reversed feeding uncouples peripheral and master clock gene rhythms and leads to
      an increased risk of disease development. The aim of this study was to determine
      the effects of clock gene uncoupling on sepsis-induced inflammation using a mouse
      cecal ligation and puncture (CLP) model. C57BL/6N mice were entrained to a 12-h
      light-dark cycle (lights on at 7 AM). Mice were permitted ad libitum feeding
      either during the night (7 PM-7 AM) or the nonphysiological light phase (7 AM-7
      PM) for a week before CLP. In daytime-fed mice, phase inversion of clock gene
      expression was observed in the liver, but not in the suprachiasmatic nucleus.
      Daytime-fed mice also had decreased body weight and food intake. Survival rate
      was significantly lower in daytime-fed mice (29%) compared with nighttime-fed
      mice (54%) 72 h after CLP (P = 0.03). Serum levels of interleukin 6 (IL-6), tumor
      necrosis factor alpha, high mobility group box 1, IL-1alpha, IL-9, eotaxin, and
      granulocyte colony-stimulating factor increased in daytime-fed mice compared with
      nighttime-fed mice after CLP. Baseline expression levels of sirtuin peroxisome 1
      and proliferator-activated receptor gamma coactivator 1alpha in the liver
      decreased in daytime-fed mice compared with nighttime-fed mice. Thus, daytime
      feeding induces clock gene uncoupling, which leads to decreased expression of
      longevity-related and energy metabolism proteins. Daytime feeding may also
      increase the levels of inflammatory cytokines, thereby increasing mortality in a
      mouse sepsis model. Our findings suggest that uncoupling of peripheral and master
      clock gene rhythms by reversed feeding exacerbates inflammatory responses. 

PMID- 24300829
TI  - Early murine polymicrobial sepsis predominantly causes renal injury.
AB  - Multiple organ failure in sepsis substantially increases mortality. This study
      examined if there was greater hepatic, pancreatic, splenic, or renal injury in
      mice that would die during sepsis induced by cecal ligation and puncture (CLP)
      compared with that of those that would survive. Mice were stratified into groups
      predicted to die (Die-P) or predicted to live (Live-P) in the first 5 days after
      CLP based on plasma interleukin 6 levels. Groups were sacrificed to harvest
      organs for histology. Separate animals were followed for survival with daily
      blood sampling to examine renal function. No significant histological evidence of
      organ injury was observed in either the Live-P or Die-P mice. Minimal hepatic
      injury occurred as plasma aspartate transaminase demonstrated less than a 2-fold
      increase over normal in both groups. In addition, pancreatic injury was minimal
      as there was also less than a 2-fold increase in plasma amylase levels. In
      contrast, blood urea nitrogen levels were nearly five times higher within 24 h in
      Die-P mice compared with those of mice predicted to live. Mice with blood urea
      nitrogen levels higher than 44 mg/dL had a 17.6 higher relative risk of dying
      (95% confidence interval, 4.5-69.4). Cystatin C, a more specific kidney function
      biomarker, was also elevated at 24 h after CLP. When the cystatin C levels were
      analyzed relative to the hours before death, rather than hours after CLP, they
      were also significantly increased in mice Dead by day 5 compared with those Alive
      after day 5. We conclude that limited liver, pancreas, and spleen injury develops
      during murine CLP-induced sepsis while significant kidney injury is present. The
      renal injury becomes worse closer to death. 

PMID- 24300830
TI  - The synthetic pentasaccharide fondaparinux attenuates myocardial ischemia
      reperfusion injury in rats via STAT-3.
AB  - Acute myocardial infarction is a leading cause of mortality and morbidity
      worldwide. Although essential for successful recovery, myocardium reperfusion is
      associated with reperfusion injury. Two major cell survival signaling cascades
      are known to be protective against ischemia-reperfusion (I/R) injury: the
      reperfusion injury salvage kinase, including Akt, extracellular signal-regulated
      kinase 1/2, and the downstream target GSK-3beta, and the survivor activating
      factor enhancement, which involves STAT-3. Pharmacologic inhibition of factor Xa
      has been shown to attenuate I/R injury, but the cellular mechanism is poorly
      understood. Our aim was to determine the role of whole blood in fondaparinux
      (FDX)-induced cardioprotection and the involvement of reperfusion injury salvage
      kinase and survivor activating factor enhancement pathways. We investigated FDX
      ability to prevent in vivo I/R injury using a transient coronary ligation rat
      model and ex vivo using a model of crystalloid-perfused isolated rat heart. In
      both models, infarct size was assessed after 120 min of reperfusion. Myocardial
      tissues were collected after 15 and 30 min of reperfusion for Western blot
      analysis. In vivo, FDX decreased infarct size by 29% and induced significant STAT
      3 and GSK-3beta phosphorylation in comparison to controls. Adding AG490, an
      inhibitor of JAK/STAT pathway, before I/R, prevented STAT-3 phosphorylation and
      abolished FDX-induced cardioprotection. On the contrary, FDX did not have an
      effect on infarct size or hemodynamic parameters in the isolated-heart model.
      Fondaparinux decreased I/R injury in vivo, but not in a crystalloid-perfused
      isolated heart. Under our experimental conditions, FDX required whole blood to be
      protective, and this beneficial effect was mediated through STAT-3
      phosphorylation. 

PMID- 24300831
TI  - Impact of kidney donor hemostasis on risk of complications after transplantation-
      preliminary outcomes.
AB  - BACKGROUND: This study analyzes the influence the of kidney donor hemostasis on
      the risk of complications in the kidney recipient after transplantation. MATERIAL
      AND METHODS: We enrolled 38 deceased kidney donors, of whom 14 donors died from a
      physical injury and the others died from ischemic or bleeding central nervous
      system stroke. The donors were categorized into 2 subgroups. If the recipient's
      postoperative period proceeded smoothly, the kidney donor was assigned to the
      uncomplicated donors (UD) group. If the recipient's postoperative period was
      complicated, the donor was assigned to the complicated (CD) Group. The CD group
      of consisted of 9 donors who died from strokes or bleedings and 2 who died from
      physical injury. We examined the antithrombin (AT) protein C (PC), complexes of
      thrombin/antithrombin (TAT), fragments F1+2 of prothrombin (F1+2), plasminogen
      (Pl), complexes of plasmin/antiplasmin (PAP), and D-dimers (D-d). RESULTS: In the
      CD group had decreased activity of AT, PC, and Pl and increased activity of F1+2,
      TAT, and D-d. The UD group had a higher level of PAP. The CD group had evidence
      of intensive blood coagulation, but the UD group had evidence of fibrinolysis.
      Fisher's exact test revealed an increased risk in recipients who received a
      kidney from the CD group. CONCLUSIONS: The hemostasis of the kidney donors had a
      correlation with the occurrence of some complications in the kidney recipients,
      especially complications connected with activation of blood coagulation. It seems
      that the activation of fibrinolysis could be positive prognostic factor, but this
      requires further investigations.

PMID- 24300832
TI  - Development and validation of a real time PCR for the detection of myxoma virus
      based on the diploid gene M000.5L/R.
AB  - The myxoma virus (MYXV) causes severe infections in European rabbits that may
      reach mortality rates up to 100% depending on the viral strain. The typical
      symptoms and lesions induced by the virus are usually enough to permit the
      correct clinical diagnosis. However, in peracute forms the infection may be
      accompanied by unspecific symptoms. Sudden death may also occur without evident
      clinical signs of myxomatosis. Likewise, a clinical diagnosis of atypical forms
      of myxomatosis (amyxomatous) is often complicated and delayed due to the
      scarceness of skin lesions. As the disease control often depends on an early and
      unequivocal diagnosis of MYXV, laboratorial methods play a relevant role in the
      confirmation of MYXV infection. This study describes the development and
      validation of a novel, high accurate real time polymerase chain reaction assay
      (rtPCR) for the detection of MYXV. Primers were designed to amplify a 125-bp
      within the gene M000.5L/R, which is duplicated in the termini of the genome and
      is unique among Leporipoxvirus. The assay was negative for SFV and other
      poxviruses and was able to detect 2.6 copies of MYXV DNA proving the
      effectiveness, specificity and sensitivity of this diagnosis tool. The rtPCR has
      been applied successfully in INIAV laboratory for routine diagnosis of
      myxomatosis since 2005. 

PMID- 24300833
TI  - Development of a loop-mediated isothermal amplification assay combined with a
      lateral flow dipstick for rapid and simple detection of classical swine fever
      virus in the field.
AB  - Classical swine fever (CSF) is a highly contagious viral disease and may cause
      heavy economic loss to farmers. The rapid, simple and accurate diagnosis of the
      disease at the frontline, for example on the farms of concern is crucial for
      disease control. This study describes the development and evaluation of a new
      loop-mediated isothermal amplification (LAMP) assay coupled with lateral flow
      dipstick (LFD) for the detection of classical swine fever virus (CSFV). This RT
      LAMP-LFD assay combines the efficient one-step isothermal amplification of CSF
      viral RNA and the simplicity of the LFD to read the results within two to five
      minutes. Seven genotypes (1.1, 1.2, 1.3, 2.1, 2.2, 2.3 and 3.1), but not genotype
      3.4, were successfully detected by the RT-LAMP-LFD assay, indicating that the
      method has a broad range of detection and can be applied in different
      geographical areas where CSFV strains belonging to these genotypes are present.
      The performance of this RT-LAMP-LFD assay was similar to that of the real-time RT
      PCR. The analytical sensitivity was about 100copies per reaction when testing two
      genotypes (1.1 and 2.3). No cross-reactivity to non-CSFV pestiviruses was
      observed. This RT-LAMP-LFD assay can be a useful novel tool for the rapid, simple
      and economic diagnosis of classical swine fever in the field. 

PMID- 24300834
TI  - Quantum teleportation of laser-generated photons with an entangled-light-emitting
      diode.
AB  - Quantum teleportation can transfer information between physical systems, which is
      essential for engineering quantum networks. Of the many technologies being
      investigated to host quantum bits, photons have obvious advantages as 'pure'
      quantum information carriers, but their bandwidth and energy is determined by the
      quantum system that generates them. Here we show that photons from fundamentally
      different sources can be used in the optical quantum teleportation protocol. The
      sources we describe have bandwidth differing by a factor over 100, but we still
      observe teleportation with average fidelity of 0.77, beating the quantum limit by
      10 standard deviations. Furthermore, the dissimilar nature of our sources exposes
      physics hidden in previous experiments, which we also predict numerically. These
      phenomena include converting qubits from Poissonian to Fock statistics, quantum
      interference, beats and teleportation for spectrally non-degenerate photons, and
      acquisition of evolving character following teleportation of a qubit. 

PMID- 24300835
TI  - Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add
      on treatment of motor symptoms in Parkinson's disease: an open label, pilot
      study.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed
      as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper
      and wider magnetic fields compared to traditional coils, may be potentially
      useful in PD, characterized by widespread, bilateral involvement of cortico
      subcortical circuits. OBJECTIVE: To evaluate the safety of repetitive deep TMS
      (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. METHODS: Twenty
      seven PD patients (aged 60.1 +/- 6.8 y; PD-duration: 6.3 +/- 2.8 y; motor-UPDRS:
      39.6 +/- 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz)
      frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor
      UPDRS off therapy was assessed before and after the last rDTMS session, together
      with safety records at each treatment session. RESULTS: No drop-outs or adverse
      events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points
      average reduction; P < 0.0001). CONCLUSIONS: High-frequency rDTMS might be a safe
      treatment for PD motor symptoms. Further placebo-controlled, randomized studies
      are warranted.

PMID- 24300836
TI  - Metacognitive mastery moderates the relationship of alexithymia with cluster C
      personality disorder traits in adults with substance use disorders.
AB  - Cluster C personality disorder traits have been observed in substance use
      disorders and linked with poorer outcome. One potential factor which may cause
      these disturbances in personality function is alexithymia, or the inability to
      name and express emotion. There may be other proximate factors which moderate the
      impact of alexithymia on the expression of cluster C traits, such as
      metacognitive mastery, which is the ability to use knowledge about mental states
      of self and others to cope with distress and solve social problems. To examine
      the possibility that mastery mediated the effects of alexithymia on cluster C
      traits, we assessed each of these constructs using the Metacognitive Assessment
      Scale Abbreviated, Toronto Alexithymia Scale and SCID II among 58 adults in an
      early phase of recovery from substance misuse disorders in a residential setting.
      Results of a multiple regression revealed that, after controlling for symptom
      severity and severity of substance misuse history, metacognitive mastery
      moderated the effect of alexithymia on number of cluster C traits. A median split
      and subsequent ANCOVA revealed that participants with higher levels of
      alexithymia and poorer metacognitive mastery had more cluster C traits than the
      other groups. These findings may have clinical implications, suggesting that
      patients with substance use disorders may benefit from treatment which addresses
      metacognitive mastery. 

PMID- 24300838
TI  - A procedure to study the effect of prolonged food restriction on heroin seeking
      in abstinent rats.
AB  - In human drug addicts, exposure to drug-associated cues or environments that were
      previously associated with drug taking can trigger relapse during abstinence.
      Moreover, various environmental challenges can exacerbate this effect, as well as
      increase ongoing drug intake. The procedure we describe here highlights the
      impact of a common environmental challenge, food restriction, on drug craving
      that is expressed as an augmentation of drug seeking in abstinent rats. Rats are
      implanted with chronic intravenous i.v. catheters, and then trained to press a
      lever for i.v. heroin over a period of 10-12 days. Following the heroin self
      administration phase the rats are removed from the operant conditioning chambers
      and housed in the animal care facility for a period of at least 14 days. While
      one group is maintained under unrestricted access to food (sated group), a second
      group (FDR group) is exposed to a mild food restriction regimen that results in
      their body weights maintained at 90% of their nonrestricted body weight. On day
      14 of food restriction the rats are transferred back to the drug-training
      environment, and a drug-seeking test is run under extinction conditions (i.e.
      lever presses do not result in heroin delivery). The procedure presented here
      results in a highly robust augmentation of heroin seeking on test day in the food
      restricted rats. In addition, compared to the acute food deprivation
      manipulations we have used before, the current procedure is a more clinically
      relevant model for the impact of caloric restriction on drug seeking. Moreover,
      it might be closer to the human condition as the rats are not required to go
      through an extinction-training phase before the drug-seeking test, which is an
      integral component of the popular reinstatement procedure. 

PMID- 24300837
TI  - The intra-rater reliability and agreement of compensatory stepping thresholds of
      healthy subjects.
AB  - The purpose of this study was to evaluate the test-retest, intra-rater
      reliability and agreement of compensatory stepping thresholds. A protocol was
      developed to establish anteroposterior single-stepping thresholds,
      anteroposterior multiple-stepping thresholds, and lateral single-stepping
      thresholds. Healthy, young subjects stood on a microprocessor-controlled
      treadmill, and responded to three series of progressively challenging surface
      translations. Subjects were instructed to "try not to step" when establishing
      single-stepping thresholds or "try to take only one step" when establishing
      multiple-stepping thresholds. Stepping thresholds were defined as the minimum
      disturbance magnitude that consistently elicited a single or second compensatory
      step. Thresholds were expressed as the ankle torque necessary to maintain upright
      posture. Thresholds studied included anterior single-stepping thresholds (tau =
      273.0 +/- 82.3 N m), posterior single-stepping, thresholds (tau = 235.5 +/- 98.0
      N m), anterior multiple-stepping thresholds (tau = 977.0 +/- 416.3 N m),
      posterior multiple-stepping thresholds (tau = 701.9 +/- 237.5 N m), stability
      side lateral single-stepping thresholds (tau = 225.7 +/- 77.7 Nm), and mobility
      side lateral single-stepping thresholds (tau = 236.8 +/- 85.4 N m). Based on
      intraclass correlation coefficients (ICC) and Bland-Altman plots, all thresholds
      demonstrated excellent reliability (ICC(2,1) = 0.87-0.97) and agreement. These
      results suggest that compensatory stepping thresholds have sufficient
      repeatability to be used in clinical and research-related assessments of fall
      risk. Additional study is needed to determine the intra- and inter-rater
      reliabilities and validity of thresholds specific to the patient populations of
      interest.

PMID- 24300839
TI  - Rhinology: clinical questions, practical answers.

PMID- 24300840
TI  - Pearls and pitfalls: medico-legal considerations for sinus surgery.
AB  - PURPOSE OF REVIEW: Patients being treated for chronic rhinosinusitis, whether via
      medical or surgical means, account for a significant percentage of all medical
      malpractice claims against otolaryngologists. In this study, we present
      suggestions to help otolaryngologists safeguard against unnecessary claims.
      RECENT FINDINGS: A significant proportion of malpractice claims associated with
      sinus surgery refer to failure of the physician to provide proper and complete
      informed consent. Poor physician communication and interpersonal skills,
      withholding information, and the impression that the physician is rushed and
      uninterested in patients' concerns appear to be associated with a higher risk of
      litigation. SUMMARY: For endoscopic sinus surgery, there are no set standards
      that delineate which complications are to be discussed; however, a frequently
      quoted suggestion has been to discuss complications specific to a procedure that
      occur in more than 1% of cases or are considered catastrophic in nature.
      Otolaryngologists should keep in mind that smell disturbances are common after
      endoscopic sinus surgery and consider discussing smell disorders as a potential
      risk during the informed consent process. If there will be a different physician
      performing the surgery, this should be discussed with the patient, and written in
      the consent. The surgeon should ensure that the patient understands the risks and
      the alternatives to surgery. Ideally, documentation is created that attests that
      the physician solicited and answered all of a patient's questions. When a
      complication occurs or if a patient is unhappy with the outcome of surgery, the
      physician should take extra care and time addressing the issue directly with the
      patient. Diligent documentation at every point is a crucial safeguarding step.

PMID- 24300841
TI  - Pediatric chronic rhinosinusitis: when should we operate?
AB  - PURPOSE OF REVIEW: The timing and role of surgery in the management of pediatric
      chronic rhinosinusitis (pCRS) remains unclear. This review attempts to summarize
      the existing literature regarding this topic. RECENT FINDINGS: pCRS is a complex
      clinical syndrome that results from multiple potential causes. Multimodal medical
      therapy is the accepted primary treatment. Adenoidectomy continues to be the
      appropriate first-line surgical therapy, and the addition of antral lavage or
      balloon dilation to this procedure may improve outcomes. Functional endoscopic
      sinus surgery (FESS) in children is safe and effective in relieving symptoms in
      the majority of patients. Failure to respond to maximal medical therapy continues
      to be a commonly cited, although poorly defined, requisite for proceeding to
      surgery. Recent literature has been focused on the outcomes after FESS rather
      than specifically defining when this intervention should be considered.
      Nevertheless, the literature seems to continue to support FESS in children with
      persistent symptoms despite adenoidectomy and appropriate medical treatment for
      pCRS. As the symptoms of chronic rhinosinusitis (CRS) may result from multiple
      underlying causes, clinicians must understand that the role and timing of surgery
      may vary with particular patients' disease. SUMMARY: Surgical management of CRS
      in children continues to be a frequent topic of study in the otolaryngology
      literature. As recent research tends to be focused on outcomes after surgery,
      further prospective studies comparing surgical versus nonsurgical treatment of
      CRS will likely be required to better define indications for proceeding to
      surgery at all.

PMID- 24300842
TI  - Peak velocity measurements in tortuous arteries with phase contrast magnetic
      resonance imaging: the effect of multidirectional velocity encoding.
AB  - OBJECTIVES: Blood flow velocity measurement with phase contrast magnetic
      resonance imaging (PC-MRI) is widely applied in clinical routine imaging.
      Usually, velocity and volumetric flow measurements are performed using
      unidirectional encoding of the through-plane velocity with a 2-dimensional (2D)
      acquisition. Single-slice acquisitions and measurements with unidirectional
      encoding, however, may lead to significant errors, especially in tortuous
      vessels, but might benefit from higher signal-to-noise ratios (SNRs). To evaluate
      the impact of volumetric acquisition and multidirectional velocity encoding,
      blood velocity measurements were performed at 3 locations in the distal internal
      carotid artery with a 3-dimensional, 3-directional time-resolved phase contrast
      (PC) sequence (4-dimensional [4D]) and a 2D acquisition with 3-directional (2D
      3dir) and through-plane velocity encoding (2D-tp) derived from the same sequence.
      MATERIALS AND METHODS: Twenty carotid arteries of 10 healthy volunteers (24-37
      years) were evaluated. For each volunteer, 1 4D acquisition and 3 2D 3
      directional PC measurements were placed according to a time-of-flight
      angiography. Unidirectionally encoded through-plane velocities were derived from
      the multidirectionally encoded 2D scan by discarding the in-plane components.
      Regions of interest were identified on the slab after postprocessing and
      visualization for the 4D data set as well as directly on the digital imaging and
      communications in medicine images for the 2D measurement. Blood flow velocity,
      volumetric flow, and SNRs were measured at carotid segments C4, C5, and C7 on
      both sides obtaining 20 values per vessel location. The quantities were tested
      for significant differences between each modality at all 3 locations with paired
      t tests. RESULTS: At the segments C5 and C7, the highest peak velocities (PVs)
      were measured with the 4D sequence, followed by 2D-3dir and 2D tp. The PV
      differences between the sequences were significant (P < 0.01) at both locations.
      At the proximal segment of the carotid siphon (C4), the PV values of the 2D-3dir
      sequence were significantly higher than the ones measured with 2D-tp. The mean PV
      value of the 4D sequence was located in between 2D-3dir and 2D-tp without
      significant differences to either of the 2D sequences. Volumetric flow
      measurements were also significantly different between 2D and 4D acquisitions,
      but without a discernible trend. The SNR analysis clearly favored 2D over 4D
      acquisitions because of higher inflow enhancement. CONCLUSIONS: The results of
      the current study show that velocity measurements with a unidirectional encoded
      through-plane PC sequence lead to a significant underestimation of velocity
      values in tortuous vessels. In all 3 evaluated segments of the distal internal
      carotid artery, multidirectional velocity encoding revealed significantly higher
      PV values than those of unidirectional velocity encoding. These results indicate
      that multidirectional encoding should be preferred to unidirectional encoding for
      velocity measurements in tortuous vessels. Furthermore, 4D PC-MRI is superior to
      2D-3dir in 2 of 3 locations. However, single-slice measurements with
      multidirectional velocity encoding have higher SNR and may be an alternative to
      4D PC-MRI with a scan time of only approximately 90 seconds per slice.

PMID- 24300843
TI  - Intraindividual comparison of diagnostic performance in patients with hepatic
      metastasis of full-dose standard and half-dose iterative reconstructions with
      dual-source abdominal computed tomography.
AB  - OBJECTIVES: The objectives of the study were to evaluate the image quality and
      diagnostic performance of sinogram-affirmed iterative reconstruction (SAFIRE) for
      detecting hepatic metastasis and to estimate the potential radiation dose
      reduction at abdominal computed tomography (CT). MATERIALS AND METHODS: Fifty
      nine consecutive patients (mean age, 59.2 years; range, 42-81 years) who had
      hepatic metastasis and who underwent dual-source abdominal CT were enrolled in
      this study. The image noise of the liver was compared between full-dose filtered
      back projection images (FD-FBP) and simulated half-dose images, which used only
      single-source projection data, and reconstructed with different strengths of
      SAFIRE (HD-SAFIRE(1-5)) by 1-way analysis of variance with Bonferroni correction.
      The diagnostic performance for hepatic metastasis was compared by logistic
      regression with the weighted least squares method and noninferiority test between
      the FD-FBP images and the half-dose sinogram-affirmed iterative reconstruction
      (HD-SAFIRE) images. RESULTS: As the SAFIRE strength increased, image noise
      decreased (P < 0.001). The images of HD-SAFIRE(2) showed similar image noise for
      liver parenchyma (13.4 Hounsfield unit [HU]), signal-to-noise ratio for liver
      parenchyma (9.2), and lesion-to-liver contrast-to-noise ratio (4.5), compared
      with the FD-FBP images (12.6 HU, P = 0.668; 9.6, P > 0.999; and 4.5, P > 0.999,
      respectively). The diagnostic accuracy for hepatic metastasis with the HD
      SAFIRE(2) images (87.5%) was not different from that of the FD-FBP images (87.5%,
      P > 0.999). The diagnostic performance of the HD-SAFIRE(2) images was also
      noninferior to that of the FD-FBP images (95% confidence interval lower limit
      difference [-9.16%] excluding the -10% clinical noninferiority limit). The mean
      (SD) volume CT dose index of FD-FBP was 11.26 (2.66) mGy, and the mean (SD)
      radiation dose equivalent associated with HD-SAFIRE was estimated to be 5.63
      (1.33) mGy. CONCLUSIONS: By applying SAFIRE2, the radiation dose could be reduced
      by up to 50% compared with the standard-of-care abdominal CT protocol without
      increasing image noise and without deteriorating diagnostic performance for the
      detection of hepatic metastasis.

PMID- 24300844
TI  - Enzymatic hydrolysis of autohydrolyzed wheat straw followed by refining to
      produce fermentable sugars.
AB  - Wheat straw was pretreated using an autohydrolysis process with different
      temperatures (160-200  degrees C) and times (10-20 min) in order to allow the
      recovery of hemicellulose in the filtrate and help open up the structure of the
      biomass for improved accessibility of enzymes during enzymatic hydrolysis.
      Autohydrolysis at 190  degrees C for 10 min provided the highest overall sugar
      (12.2/100g raw wheat straw) in the autohydrolysis filtrate and recovered 62.3% of
      solid residue. Before enzymatic hydrolysis, the pulps obtained from each
      pretreatment condition were subjected to a refining post-treatment to improve
      enzyme accessibility. Enzymatic hydrolysis was performed for all the pretreated
      solids with and without refining post-treatment at the enzyme loadings of 4 and
      10 FPU/g oven dry substrate for 96 h. A total of 30.4 g sugars can be recovered
      from 100g wheat straw at 180  degrees C for 20 min with 4 FPU/g enzyme charge.

PMID- 24300845
TI  - Thermogravimetric investigation on the degradation properties and combustion
      performance of bio-oils.
AB  - The degradation properties and combustion performance of raw bio-oil, aged bio
      oil, and bio-oil from torrefied wood were investigated through thermogravimetric
      analysis. A three-stage process was observed for the degradation of bio-oils,
      including devolatilization of the aqueous fraction and light compounds,
      transition of the heavy faction to solid, and combustion of carbonaceous
      residues. Pyrolysis kinetics parameters were calculated via the reaction order
      model and 3D-diffusion model, and combustion indexes were used to qualitatively
      evaluate the thermal profiles of tested bio-oils for comparison with commercial
      oils such as fuel oils. It was found that aged bio-oil was more thermally
      instable and produced more combustion-detrimental carbonaceous solid. Raw bio-oil
      and bio-oil from torrefied wood had comparable combustion performance to fuel
      oils. It was considered that bio-oil has a potential to be mixed with or totally
      replace the fuel oils in boilers. 

PMID- 24300846
TI  - A growth inhibitory model with SO(x) influenced effective growth rate for
      estimation of algal biomass concentration under flue gas atmosphere.
AB  - A theoretical model for the prediction of biomass concentration under rice husk
      flue gas emission has been developed. The growth inhibitory model (GIM) considers
      the CO2 mass transfer rate, the critical SOx concentration and its role in pH
      based inter-conversion of bicarbonate. The calibration and subsequent validation
      of the growth profile of Nannochloropsis limnetica at 2% and 10% (v/v) CO2 showed
      that the predicted values were consistent with the measured values, with r(2)
      being 0.96 and 0.98, respectively, and p<0.001 in both cases. The constants used
      in the GIM for the prediction of biomass have been justified using sensitivity
      analysis. GIM applicability was defined as +/-30% of the calibrated flow rate
      (3.0 L min(-1)). This growth model can be applied to predict algal growth in
      photo-bioreactors treated with flue gas in the generation of biomass feed stock
      for biofuel production.

PMID- 24300847
TI  - Ammonia removal in food waste anaerobic digestion using a side-stream stripping
      process.
AB  - Three 35-L anaerobic digesters fed on source segregated food waste were coupled
      to side-stream ammonia stripping columns and operated semi-continuously over 300
      days, with results in terms of performance and stability compared to those of a
      control digester without stripping. Biogas was used as the stripping medium, and
      the columns were operated under different conditions of temperature (55, 70, 85 
      degrees C), pH (unadjusted and pH 10), and RT (2-5 days). To reduce digester TAN
      concentrations to a useful level a high temperature (>=70  degrees C) and a pH of
      10 were needed; under these conditions 48% of the TAN was removed over a 138-day
      period without any detrimental effects on digester performance. Other effects of
      the stripping process were an overall reduction in digestate organic nitrogen
      containing fraction compared to the control and a recovery in the acetoclastic
      pathway when TAN concentration was 1770+/-20 mg kg(-1).

PMID- 24300848
TI  - Enhanced glucose yield and structural characterization of corn stover by sodium
      carbonate pretreatment.
AB  - Na2CO3 was employed as an efficient yet cheap alkaline catalyst for the
      pretreatment of corn stover. To systematically obtain an optimal condition, the
      effects of critical pretreatment parameters including Na2CO3 concentration (2
      6%), temperature (120-160  degrees C), and reaction time (10-30 min) on glucose
      yield were evaluated in lab-scale using response surface methodology. The best
      conditions were found to be Na2CO3 of 4.1%, temperature of 142.6  degrees C, and
      reaction time of 18.0 min, under which glucose yield reached to 267.5 g/kg
      biomass. Physical properties, based on scanning electron microscopy (SEM)
      imagery, surface area, pore volume and size, and crystallinity of pretreated corn
      stover, were examined. The Na2CO3 pretreatment apparently damaged the surface and
      altered structural features of corn stover, which resulted in the enhancement of
      enzymatic of hydrolysis. These results evidently support that Na2CO3 is indeed a
      robust and feasible catalyst for pretreating lignocellulosic biomass.

PMID- 24300849
TI  - Improved method for the preparation of a human cell-based, contact model of the
      blood-brain barrier.
AB  - The blood-brain barrier (BBB) comprises impermeable but adaptable brain
      capillaries which tightly control the brain environment. Failure of the BBB has
      been implied in the etiology of many brain pathologies, creating a need for
      development of human in vitro BBB models to assist in clinically-relevant
      research. Among the numerous BBB models thus far described, a static (without
      flow), contact BBB model, where astrocytes and brain endothelial cells (BECs) are
      cocultured on the opposite sides of a porous membrane, emerged as a simplified
      yet authentic system to simulate the BBB with high throughput screening capacity.
      Nevertheless the generation of such model presents few technical challenges.
      Here, we describe a protocol for preparation of a contact human BBB model
      utilizing a novel combination of primary human BECs and immortalized human
      astrocytes. Specifically, we detail an innovative method for cell-seeding on
      inverted inserts as well as specify insert staining techniques and exemplify how
      we use our model for BBB-related research. 

PMID- 24300850
TI  - Individual differences in reading aloud: a mega-study, item effects, and some
      models.
AB  - Normal individual differences are rarely considered in the modelling of visual
      word recognition--with item response time effects and neuropsychological
      disorders being given more emphasis--but such individual differences can inform
      and test accounts of the processes of reading. We thus had 100 participants read
      aloud words selected to assess theoretically important item response time effects
      on an individual basis. Using two major models of reading aloud--DRC and CDP+--we
      estimated numerical parameters to best model each individual's response times to
      see if this would allow the models to capture the effects, individual differences
      in them and the correlations among these individual differences. It did not. We
      therefore created an alternative model, the DRC-FC, which successfully captured
      more of the correlations among individual differences, by modifying the locus of
      the frequency effect. Overall, our analyses indicate that (i) even after
      accounting for individual differences in general speed, several other individual
      difference in reading remain significant; and (ii) these individual differences
      provide critical tests of models of reading aloud. The database thus offers a set
      of important constraints for future modelling of visual word recognition, and is
      a step towards integrating such models with other knowledge about individual
      differences in reading.

PMID- 24300851
TI  - Can Streamlined Multicriteria Decision Analysis Be Used to Implement Shared
      Decision Making for Colorectal Cancer Screening?
AB  - BACKGROUND: Current US colorectal cancer screening guidelines that call for
      shared decision making regarding the choice among several recommended screening
      options are difficult to implement. Multicriteria decision analysis (MCDA) is an
      established method well suited for supporting shared decision making. Our study
      goal was to determine whether a streamlined form of MCDA using rank-order-based
      judgments can accurately assess patients' colorectal cancer screening priorities.
      METHODS: We converted priorities for 4 decision criteria and 3 subcriteria
      regarding colorectal cancer screening obtained from 484 average-risk patients
      using the analytic hierarchy process (AHP) in a prior study into rank-order-based
      priorities using rank order centroids. We compared the 2 sets of priorities using
      Spearman rank correlation and nonparametric Bland-Altman limits of agreement
      analysis. We assessed the differential impact of using the rank-order-based
      versus the AHP-based priorities on the results of a full MCDA comparing 3
      currently recommended colorectal cancer screening strategies. Generalizability of
      the results was assessed using Monte Carlo simulation. RESULTS: Correlations
      between the 2 sets of priorities for the 7 criteria ranged from 0.55 to 0.92. The
      proportions of differences between rank-order-based and AHP-based priorities that
      were more than +/-0.15 ranged from 1% to 16%. Differences in the full MCDA
      results were minimal, and the relative rankings of the 3 screening options were
      identical more than 88% of the time. The Monte Carlo simulation results were
      similar. CONCLUSIONS: Rank-order-based MCDA could be a simple, practical way to
      guide individual decisions and assess population decision priorities regarding
      colorectal cancer screening strategies. Additional research is warranted to
      further explore the use of these methods for promoting shared decision making.

PMID- 24300852
TI  - CD33 target validation and sustained depletion of AML blasts in long-term
      cultures by the bispecific T-cell-engaging antibody AMG 330.
AB  - Antibody-based immunotherapy represents a promising strategy to target and
      eliminate chemoresistant leukemic cells. Here, we evaluated the CD33/CD3
      bispecific T cell engaging (BiTE) antibody (AMG 330) for its suitability as a
      therapeutic agent in acute myeloid leukemia (AML). We first assessed CD33
      expression levels by flow cytometry and found expression in >99% of patient
      samples (n = 621). CD33 was highest expressed in AMLs with NPM1 mutations (P <
      .001) and lower in AMLs with complex karyotypes and t(8;21) translocations (P <
      .001). Furthermore, leukemic stem cells within the CD34(+)/CD38(-) compartment
      displayed CD33 at higher levels than healthy donor stem cells (P = .047). In MS-5
      feeder cell-based long-term cultures that supported the growth of primary AML
      blasts for up to 36 days, AMG 330 efficiently recruited and expanded residual
      CD3(+)/CD45RA(-)/CCR7(+) memory T cells within the patient sample. Even at low
      effector to target ratios, the recruited T cells lysed autologous blasts
      completely in the majority of samples and substantially in the remaining samples
      in a time-dependent manner. This study provides the first correlation of CD33
      expression levels with AML genotype in a comprehensive analysis of adult
      patients. Targeting CD33 ex vivo using AMG 330 in primary AML samples led to T
      cell recruitment and expansion and remarkable antibody-mediated cytotoxicity,
      suggesting efficient therapeutic potential in vivo. 

PMID- 24300853
TI  - Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with
      a marginal-zone origin: is this a distinct entity?
AB  - The biological and clinical significance of a clonal B-cell lymphocytosis with an
      immunophenotype consistent with marginal-zone origin (CBL-MZ) is poorly
      understood. We retrospectively evaluated 102 such cases with no clinical evidence
      to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell
      population with Matutes score <=2 in all cases; 19/102 were weakly CD5 positive
      and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly
      mixed patterns of small B-lymphocytic infiltration. A total of 48/66 (72.7%)
      cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4
      34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene
      rearrangements. With a median follow-up of 5 years, 85 cases remain stable (group
      A), whereas 17 cases (group B) progressed, of whom 15 developed splenomegaly. The
      clonal B-cell count, degree of marrow infiltration, immunophenotypic, or
      immunogenetic findings at diagnosis did not distinguish between the 2 groups.
      However, deletions of chromosome 7q were confined to group A and complex
      karyotypes were more frequent in group B. Although CBL-MZ may antedate SMZL/SLLU,
      most cases remain stable over time. These cases, not readily classifiable within
      the World Heath Organization classification, raise the possibility that CBL-MZ
      should be considered as a new provisional entity within the spectrum of clonal MZ
      disorders. 

PMID- 24300854
TI  - Junctional adhesion molecule-A suppresses platelet integrin alphaIIbbeta3
      signaling by recruiting Csk to the integrin-c-Src complex.
AB  - Fibrinogen binding to activated integrin induces outside-in signaling that
      results in stable platelet aggregates and clot retraction. How integrin
      alphaIIbbeta3 is discouraged from spontaneous activation is not known. We have
      recently shown that junctional adhesion molecule-A (JAM-A) renders protection
      from thrombosis by suppressing integrin outside-in signaling. In this study, we
      show that JAM-A associates with integrin alphaIIbbeta3 in resting platelets and
      dissociates upon platelet activation by agonists. We also show that integrin
      associated JAM-A is tyrosine phosphorylated and is rapidly dephosphorylated upon
      platelet activation. C-terminal Src kinase (Csk) binds to tyrosine phosphorylated
      JAM-A through its Src homology 2 domain. Thus, JAM-A recruits Csk to the integrin
      c-Src complex in resting platelets. Csk, in turn, keeps integrin-associated c-Src
      in an inactive state by phosphorylating Y(529) in its regulatory domain. Absence
      of JAM-A results in impaired c-SrcY(529) phosphorylation and augmentation of
      outside-in signaling-dependent c-Src activation. Our results strongly suggest
      that tyrosine-phosphorylated JAM-A is a Csk-binding protein and functions as an
      endogenous inhibitor of integrin signaling. JAM-A recruits Csk to the integrin-c
      Src complex, where Csk negatively regulates c-Src activation, thereby suppressing
      the initiation of outside-in signaling. Upon agonist stimulation, JAM-A is
      dephosphorylated on the tyrosine, allowing the dissociation of Csk from the
      integrin complex, and thus facilitating outside-in signaling. 

PMID- 24300857
TI  - The effects of race and socioeconomic status on immunomodulator and anti-tumor
      necrosis factor use among ambulatory patients with inflammatory bowel disease in
      the United States.
AB  - OBJECTIVES: Health-care disparities exist for patients of minority race and low
      socioeconomic status (SES) in many chronic disease states, but little is known
      regarding health-care disparities for patients with inflammatory bowel disease
      (IBD). Using nationally representative data, we sought to determine whether use
      of immunomodulators and anti-tumor necrosis factor (TNF) agents differed by
      race/ethnicity and SES among ambulatory patients with IBD. METHODS: We used data
      from the National Ambulatory Medical Care Survey and the National Hospital
      Ambulatory Medical Care Survey from 1998 to 2010. We identified visits associated
      with IBD and the medications associated with those visits. Race/ethnicity and SES
      were characterized. The frequency of immunomodulator and anti-TNF use over time
      was assessed. We performed analyses accounting for the survey's complex
      multistage probability sampling design. Associations between race/ethnicity, SES
      and IBD medication use were identified. RESULTS: A total of 26,400,000 visits for
      patients with IBD occurred in the United States from 1998 to 2010. Seventy-six
      per cent of visits were for whites, 9% were for blacks, 7% were for Hispanics,
      and 2% were for Asians. Sixty-one per cent of visits were privately insured,
      whereas 7% had Medicaid coverage. From 1998 to 2010, the proportion of visits
      associated with immunomodulators increased from 6 to 13%, whereas the proportion
      associated with anti-TNF agents increased from <1 to 14%. In adjusted analyses,
      visits with Medicaid were three times more likely to be associated with
      immunomodulators than visits with private insurance, but there were no
      race/ethnicity-based differences in immunomodulator use. There were no
      race/ethnicity- or SES-based differences in anti-TNF therapy. CONCLUSIONS: Using
      nationally representative data over a 13-year time period, we found no evidence
      of disparities in medical therapy for IBD among visits with minority
      race/ethnicity or low SES.

PMID- 24300858
TI  - Anti-adhesion therapies and the rule of 3 for rare events.
AB  - During the open-label trial of natalizumab for Crohn's disease, an isolated case
      of progressive multifocal leukoencephalopathy (PML) was found. This prompted a
      more careful review by regulators, physicians, and the pharmaceutical industry. A
      new gut-specific monoclonal antibody, vedolizumab, has been shown to be effective
      in inflammatory bowel disease, and in continued trials no patients have developed
      PML. Given the mortality of PML and lack of effective treatments, patients may
      remain concerned that PML is a possible risk factor. So, going forward, how do we
      quantify the risk of this serious adverse event? This review details how we
      define the maximum risk when no (or very few) events have occurred with an easy
      to-use equation. 

PMID- 24300855
TI  - Oxidative stress in angiogenesis and vascular disease.
AB  - Despite the damaging effect on tissues at a high concentration, it has been
      gradually established that oxidative stress plays a positive role during
      angiogenesis. In adults, physiological or pathological angiogenesis is initiated
      by tissue demands for oxygen and nutrients, resulting in a hypoxia/reoxygenation
      cycle, which, in turn promotes the formation of reactive oxygen species (ROS).
      The ROS can be generated either endogenously, through mitochondrial electron
      transport chain reactions and nicotinamide adenine dinucleotide phosphate
      oxidase, or exogenously, resulting from exposure to environmental agents, such as
      ultraviolet or ionizing radiation. In many conditions, ROS promotes angiogenesis,
      either directly or via the generation of active oxidation products, including
      peroxidized lipids. The latter lipid metabolites are generated in excess during
      atherosclerosis, thereby linking atherogenic processes and pathological
      angiogenesis. Although the main mechanism of oxidative stress-induced
      angiogenesis involves hypoxia-inducible factor/vascular endothelial growth factor
      (VEGF) signaling, recent studies have identified several pathways that are VEGF
      independent. This review aims to provide a summary of the past and present views
      on the role of oxidative stress as a mediator and modulator of angiogenesis, and
      to highlight newly identified mechanisms. 

PMID- 24300859
TI  - Images of the month: mediastinal pseudocyst; endoscopic stent drainage of
      peripouch abscess.

PMID- 24300864
TI  - Intravenous iron for the treatment of iron deficiency in IBD: the pendulum is
      swinging.
AB  - Intravenous (IV) iron therapy has been a major asset in the management of
      refractory iron-deficiency anemia in inflammatory bowel disease (IBD) and other
      diseases. However, the cost-effectiveness of parenteral substitution as the first
      line treatment of this condition in IBD has been questioned. A study published by
      Reinisch et al. in this issue of the journal fails to show non-inferiority of
      iron isomaltose 1,000, a novel high-dose IV preparation, compared to oral iron
      sulfate. 

PMID- 24300865
TI  - ADR improvement: the result of the intervention or the Hawthorne effect.

PMID- 24300866
TI  - Response to Sewitch et al.

PMID- 24300867
TI  - Response to Neis et al.

PMID- 24300868
TI  - The role of diagnostic colonoscopy in constipation: a quality improvement
      project.

PMID- 24300869
TI  - Response to Surawicz et al.

PMID- 24300870
TI  - Hepatocellular carcinoma and smoking: oblivion or contempt?

PMID- 24300871
TI  - Response to Braillon.

PMID- 24300872
TI  - Western dietary pattern and sedentary life: independent effects of diet and
      physical exercise intensity on NAFLD.

PMID- 24300873
TI  - No increase in Epstein-Barr virus viral load in a group of 30 asymptomatic
      patients with Crohn's disease.

PMID- 24300874
TI  - Neurofibroma of the esophagus complicating Von Recklinghausen's
      neurofibromatosis.

PMID- 24300875
TI  - Genetics of drug-induced hepatotoxicity toxicity in Gilbert's syndrome.

PMID- 24300876
TI  - N-butyl-2-cyanoacrylate in gastric varices: a cause for recurrent sepsis.

PMID- 24300877
TI  - The tug sign: an endoscopic feature of eosinophilic esophagitis.

PMID- 24300879
TI  - Basic research: MK2 and p53 - a lethal pairing.

PMID- 24300880
TI  - Gastrointestinal cancer: targeted therapies in gastric cancer-the dawn of a new
      era.
AB  - The international phase III REGARD study demonstrated improved overall survival
      with ramucirumab as second-line therapy for patients with advanced-stage gastric
      and gastroesophageal junction adenocarcinoma. As a novel biological treatment, is
      ramucirumab also the harbinger of a new era of targeted therapies in this
      prevalent and highly morbid disease?

PMID- 24300881
TI  - Paediatric oncology: frailty after childhood cancer.

PMID- 24300882
TI  - Haematological cancer: the importance of being stringent.

PMID- 24300883
TI  - Trends of hepatitis B notification rates in Turkey, 1990 to 2012.
AB  - Turkey is a country with intermediate endemicity for hepatitis B, and
      approximately 4% of the population are HBsAg-positive. A number of measures have
      been implemented to prevent hepatitis B infection. In 1998, hepatitis B antigen
      was included in the national immunisation programme, and infants have since been
      vaccinated with three doses. Catch-up strategies, vaccination for high risk
      groups and screening measures were also adopted. The aim of this study was to
      evaluate the impact of the prevention and control strategies on hepatitis B
      notification rates in Turkey in the period from 1990 to 2012, using data from the
      national surveillance system. Secular trends revealed that rates showed an
      initial increasing trend, followed by a steady decline from 2005. The most
      dramatic decline occurred among children younger than 15 years, highlighting the
      benefits of vaccination and catch-up strategies. However, vaccination cannot
      fully explain the decrease in this age group. Socioeconomic development, through
      interrupting the horizontal transmission may also have contributed. After 2005, a
      steady decline was achieved also among those 15 years and older. The rates in
      adults were higher, which indicates that stronger prevention measures are needed
      to target this group, particularly men.

PMID- 24300884
TI  - Hepatitis B prevalence in Denmark - an estimate based on nationwide registers and
      a national screening programme, as on 31 December 2007.
AB  - The prevalence of chronic hepatitis B virus (HBV) infection in Denmark is not
      clear. The primary aim of this study was to estimate the prevalence of chronic
      HBV infection in Denmark. The capture-recapture method was used to estimate the
      total population diagnosed with chronic HBV infection in Denmark using four
      nationwide registers. The population with undiagnosed chronic HBV infection was
      estimated by incorporating data from a two-year nationwide HBsAg screening
      programme in pregnant women. We identified 4,466 individuals with chronic HBV
      infection in the four registers until the end of 2007, and the capture-recapture
      estimate of the total population diagnosed with chronic hepatitis B was 7,112
      (95% confidence interval (CI): 6,953-10,747). Only 17% of the identified patients
      attended recommended clinical care according to national guidelines. Including
      undiagnosed patients, the current population alive with HBV infection was 10,668
      (95% CI: 10,224-16,164), corresponding to a prevalence of 0.24% (95% CI: 0.23
      0.37%) in the Danish population older than 15 years. The estimated prevalence of
      chronic HBV infection among adults in Denmark was lower than reported from other
      northern European countries. Only half of the infected population had been
      diagnosed, and a minority attended specialised clinical care.

PMID- 24300885
TI  - A validation of the use of names to screen for risk of chronic hepatitis B in
      Victoria, Australia, 2001 to 2010.
AB  - The burden of chronic hepatitis B (CHB) is increasing in Australia, particularly
      in those born in the Asia-Pacific region, and nearly half are undiagnosed.
      Primary care clinicians have a key role in diagnosing CHB, however identification
      of patients at risk is hindered by lack of awareness and limited information on
      country of birth in patient records. This study evaluates the potential of a
      validated list of names associated with Asian country of birth as a screening
      tool to predict risk of CHB, by comparing it with surveillance records for all
      people diagnosed with CHB or salmonellosis in Victoria from 2001 to 2010, and
      analysed using standard screening tools. Name list match was associated with CHB
      notification, with over 60% of cases having one name matching the list
      (sensitivity), and nearly one third matching both given name and surname; less
      than 15% and 2% of salmonellosis notifications matched for one name and both
      names, respectively (false positives). These results show that more than half of
      notified cases of CHB would have been identified by this name list, and that it
      could be used in support of initiatives to improve diagnosis of patients with
      diseases associated with country of birth when limited information is available.

PMID- 24300886
TI  - Molecular epidemiology of hepatitis C virus genotypes and subtypes among
      injecting drug users in Hungary.
AB  - The aim of this study was to determine the geographical distribution of hepatitis
      C virus genotypes/subtypes among people who inject drugs (PWID) recruited at 22
      needle exchange sites and drug outpatient services in all seven Planning and
      Statistical Regions of Hungary. Of 198 such PWID, 147 (74.2%), 45 (22.7%) and six
      (3.0%) carried genotype 1, 3 or 4, respectively, and 31 (72.1%) of the 43
      genotype 1 sequences were of subtype 1a. Genotype 3 was significantly more
      prevalent in provincial towns than in the capital, Budapest. Injecting for a
      longer period and an older age both correlated with a higher prevalence of
      genotype 3, suggesting possible future changes in genotype distribution. The
      distributions of hepatitis C virus genotypes/ subtypes differed significantly
      between the tested PWID and the general population. The identification of
      genotype 3 reflected its worldwide occurrence among PWID. Our results underline
      the importance of genotyping before treatment, especially among people who have
      ever injected drugs in Hungary.

PMID- 24300887
TI  - Spatial and temporal analysis of human infection with avian influenza A(H7N9)
      virus in China, 2013.
AB  - Descriptive and geographic information system methods were used to depict the
      spatial and temporal characteristics of the outbreak of human infection with a
      novel avian influenza A(H7N9) virus in mainland China, the peak of which appeared
      between 28 March and 18 April 2013. As of 31 May 2013, there was a total of 131
      reported human infections in China, with a cumulative mortality of 29% (38/131).
      The outbreak affected 10 provinces, with 106 of the cases being concentrated in
      the eastern coastal provinces of Zhejiang, Shanghai and Jiangsu. Statistically
      significant spatial clustering of cumulative human cases was identified by the
      Cuzick-Edwards' k-nearest neighbour method. Three spatio-temporal clusters of
      cases were detected by space-time scan analysis. The principal cluster covered 18
      counties in Zhejiang during 3 to 18 April (relative risk (RR): 26.39;p<0.0001),
      while two secondary clusters in March and April covered 21 counties along the
      provincial boundary between Shanghai and Jiangsu (RR: 6.35;p<0.0001) and two
      counties in Jiangsu (RR: 72.48;p=0.0025). The peak of the outbreak was in the
      eastern coastal provinces of Zhejiang, Shanghai and Jiangsu that was
      characterised by statistically significant spatio-temporal aggregation, with a
      particularly high incidence in March and April 2013.

PMID- 24300888
TI  - Special Eurobarometer: use of antibiotics declining in the European Union but
      much work still needed.

PMID- 24300889
TI  - Common antigens prediction in bacterial bioweapons: a perspective for vaccine
      design.
AB  - Bioweapons (BWs) are a serious threat to mankind and the lack of efficient
      vaccines against bacterial bioweapons (BBWs) further worsens the situation in
      face of BW attack. Experts believe that difficulties in detection and ease in
      dissemination of deadly pathogens make BW a better option for attack compared to
      nuclear weapons. Molecular biology techniques facilitate the use of genetically
      modified BBWs thus creating uncertainty on which bacteria will be used for BW
      attack. In the present work, available resources such as proteomic sequences of
      BBWs, protective antigenic proteins (PAPs) reported in Protegen database and
      VaxiJen dataset, and immunogenic epitopes in immune epitope database (IEDB) were
      used to predict potential broad-specific vaccine candidates against BBWs.
      Comparison of proteomes sequences of BBWs and their analyses using in-house PERL
      scripts identified 44 conserved proteins and many of them were known to be
      immunogenic. Comparison of conserved proteins against PAPs identified six either
      as PAPs or their homologues with a potential of providing protection against
      multiple pathogens. Similarly, mapping of conserved proteins against
      experimentally known IEDB epitopes identified six epitopes which had exact
      epitope match in four proteins including three from earlier predicted six PAPs.
      These epitopes were also reported to provide protection against several
      pathogens. In the backdrop of conserved heat shock GroEL protein from Salmonella
      enterica providing protection against five diverse bacterial pathogens involved
      in different diseases, and synthetic proteins produced by combination of epitopes
      from Mycobacterium tuberculosis and 4 viruses providing protection against both
      bacterium and viruses, the identified putative immunogenic conserved proteins and
      immune-protective epitopes can further be explored for their potential as broad
      specific vaccine candidates against BBWs. 

PMID- 24300890
TI  - Beta-adrenergic antagonist effects on a novel cognitive flexibility task in
      rodents.
AB  - Previous work examining animal models of cognitive flexibility have focused on
      tasks where animals are required to shift between cues in order to reach a food
      reward from among a limited set of choices. Performance by nonhuman animals on
      these tasks, including reversal learning, intradimensional set-shifting, and
      extradimensional set-shifting, are affected by pharmacological action on
      serotonergic, dopaminergic, and alpha-adrenergic, but not beta-adrenergic
      receptors. However, beta-adrenergic antagonists, such as propranolol, are widely
      utilized for conditions such as test anxiety. Propranolol improves performance in
      humans during cognitive flexibility tasks where there is a broad set of potential
      solutions. The current investigation utilized a digging task where the rodent
      must develop a novel solution in order to obtain a reward. Similar to the effects
      observed in humans, propranolol improved performance on this task, while not
      affecting performance on set-shifting tasks, as with previous animal studies.
      This may allow future investigation of the neurobiological mechanism by which
      propranolol affects context-specific anxiety, and could provide insight into the
      neurobiology of creativity. 

PMID- 24300891
TI  - Hippocampal lesions in homing pigeons do not impair feature-quality or feature
      quantity discrimination.
AB  - The role of the avian hippocampal formation (HF) in spatial cognition is well
      demonstrated. However, it remains uncertain if the avian hippocampus, like its
      mammalian counterpart, has a role in the integration of elements that could
      compose a memory independent of space. The two experiments in the current study
      examined whether the HF of homing pigeons (Columba livia) was required to encode
      into memory a discriminative representation of food quality (Experiment 1) and
      quantity (Experiment 2) with different food bowl-features. Pigeons were exposed
      to an array of different colored bowls, two of which contained food rewards
      differing in preferred quality or quantity. To render space irrelevant for memory
      encoding, the location of the food-rewarded bowls was altered between each trial,
      while the features of the rewarded bowls remained constant. Both groups learned
      the feature-based quality and quantity discrimination tasks and no difference in
      performance between control pigeons and those with bilateral lesions of the
      hippocampus were found. The findings do not support the hypothesis that the avian
      HF is recruited when only non-spatial elements are integrated into a unified
      memory. From the current study, and the literature as a whole, it appears that
      the avian HF, unlike the mammalian hippocampus, may play no necessary role in
      memory processes where space is irrelevant.

PMID- 24300892
TI  - The GABA-synthetic enzyme GAD65 controls circadian activation of conditioned fear
      pathways.
AB  - Circadian fluctuations of fear and anxiety symptoms are observable in persons
      with post-traumatic stress disorder, generalized anxiety, and panic disorder;
      however, the underlying neurobiological mechanisms are not sufficiently
      understood. In the present study, we investigated the putative role of inhibitory
      neurotransmission in the circadian fluctuation of fear symptoms, using mice with
      genetic ablation of the gamma-amino butyric acid (GABA) synthesizing isoenzyme,
      glutamic acid decarboxylase GAD65. We observed in these mutant mice an altered
      expression of conditioned fear with a profound reduction of freezing, and an
      increase of hyperactivity bouts occurring only when both fear conditioning
      training and retrieval testing were done at the beginning of their active phase.
      Mutants further showed an increased arousal response at this time of the day,
      although, circadian rhythm of home cage activity was unaltered. Hyperactivity and
      reduced freezing during fear memory retrieval were accompanied by an increased
      induction of the immediate early gene cFos suggesting hyperactivation of the
      hippocampus, amygdala, and medial hypothalamus. Our data suggest a role of GAD65
      mediated GABA synthesis in the encoding of circadian information to fear memory.
      GAD65 deficits in a state-dependent manner result in increased neural activation
      in fear circuits and elicit panic-like flight responses during fear memory
      retrieval. 

PMID- 24300893
TI  - T lymphocyte responses during early enteric Mycobacterium avium subspecies
      paratuberculosis infection in cattle.
AB  - Johne's disease (JD) is a costly intestinal disease of ruminants caused by
      Mycobacterium avium subspecies paratuberculosis (Map), which is transmitted to
      perinatal calves by the fecal-oral route. Disease control efforts focus on
      identification and culling of infected cattle from herds; therefore failure to
      identify animals early is a major obstacle to reducing transmission. Development
      of host immunity during early JD remain incompletely characterized so detecting
      subclinical JD using immunologic techniques is a substantial challenge in the
      field. Development of a test with high sensitivity and specificity is a major
      research goal with significant implications for the cattle industry. The
      objectives of this study were to compare early Map-specific T lymphocyte
      responses in naive, experimentally Map infected and Map vaccinated calves using a
      subcutaneous matrigel biopolymer-based assay. We examined the phenotype of
      recruited lymphocytes and local interferon gamma (IFNgamma) production within
      subcutaneously placed matrigel containing Map antigen 30 days after
      experimentally induced intestinal Map infection or Map vaccination. We show that
      IFNgamma-secreting CD4+ T cells are recruited to matrigel sites in vaccinated but
      not infected or naive calves. gammadelta T cells recruited to matrigel sites of
      Map-infected calves were mostly WC1-, while gammadelta T cells recruited to
      matrigel sites of Map-vaccinated calves were predominantly WC1+. IFNgamma at
      matrigel sites was a discriminating factor between infected calves, naive calves
      and vaccinated calves. These data contribute to our understanding of early anti
      Map immunity, and may be useful for detecting early intestinal Map infections in
      calves or for enhancing our ability to discriminate between Map-infected and Map
      vaccinated calves.

PMID- 24300894
TI  - On-chip evaluation of platelet adhesion and aggregation upon exposure to
      mesoporous silica nanoparticles.
AB  - Mesoporous silica nanoparticles are promising drug delivery agents; however,
      their interaction with various in vivo biological components is still under
      investigation. In this work, the impact of sub-50 nm diameter mesoporous silica
      nanoparticles on platelet function is investigated using a microfluidic platform
      to model blood vessel characteristics. Platelet adhesion and aggregation in the
      presence of mesoporous silica nanoparticles is investigated, controlling whether
      or not platelets are activated ahead of nanoparticle exposure. The results
      indicate that nanoparticles slightly compromise platelet adhesion to endothelial
      cells at low nanoparticle doses, but that high nanoparticle doses significantly
      increase the number of platelet adhesion events, leading to higher probability
      for uncontrolled platelet actions (e.g. clot formation in vivo). High
      nanoparticle doses also induced platelet aggregation. While platelet activation
      and aggregation occurred, in no case did nanoparticle exposure result in
      significant loss of platelet viability; as such, this work clearly demonstrates
      that aspects besides viability, such as cellular adhesion and interaction with
      other cell types, have to be considered in the context of nanotoxicology. This
      simple and highly adaptable analytical platform will be useful for further
      nanotoxicity studies involving other nanoparticle and cell types. 

PMID- 24300895
TI  - HES1 is a master regulator of glucocorticoid receptor-dependent gene expression.
AB  - Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription
      factor that is a key regulator of development and organogenesis. However, little
      is known about the role of HES1 after birth. Glucocorticoids, primary stress
      hormones that are essential for life, regulate numerous homeostatic processes
      that permit vertebrates to cope with physiological challenges. The molecular
      actions of glucocorticoids are mediated by glucocorticoid receptor-dependent
      regulation of nearly 25% of the genome. Here, we established a genome-wide
      molecular link between HES1 and glucocorticoid receptors that controls the
      ability of cells and animals to respond to stress. Glucocorticoid signaling
      rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent
      repression of HES1 was necessary for the glucocorticoid receptor to regulate many
      of its target genes. Mice with conditional knockout of HES1 in the liver
      exhibited an expanded glucocorticoid receptor signaling profile and aberrant
      metabolic phenotype. Our results indicate that HES1 acts as a master repressor,
      the silencing of which is required for proper glucocorticoid signaling. 

PMID- 24300896
TI  - Lysine methylation promotes VEGFR-2 activation and angiogenesis.
AB  - Activation of vascular endothelial growth factor receptor-2 (VEGFR-2), an
      endothelial cell receptor tyrosine kinase, promotes tumor angiogenesis and ocular
      neovascularization. We report the methylation of VEGFR-2 at multiple Lys and Arg
      residues, including Lys(1041), a residue that is proximal to the activation loop
      of the kinase domain. Methylation of VEGFR-2 was independent of ligand binding
      and was not regulated by ligand stimulation. Methylation of Lys(1041) enhanced
      tyrosine phosphorylation and kinase activity in response to ligands.
      Additionally, interfering with the methylation of VEGFR-2 by pharmacological
      inhibition or by site-directed mutagenesis revealed that methylation of Lys(1041)
      was required for VEGFR-2-mediated angiogenesis in zebrafish and tumor growth in
      mice. We propose that methylation of Lys(1041) promotes the activation of VEGFR-2
      and that similar posttranslational modification could also regulate the activity
      of other receptor tyrosine kinases. 

PMID- 24300898
TI  - Isolation of microvascular endothelial tubes from mouse resistance arteries.
AB  - The control of blood flow by the resistance vasculature regulates the supply of
      oxygen and nutrients concomitant with the removal of metabolic by-products, as
      exemplified by exercising skeletal muscle. Endothelial cells (ECs) line the
      intima of all resistance vessels and serve a key role in controlling diameter
      (e.g. endothelium-dependent vasodilation) and, thereby, the magnitude and
      distribution of tissue blood flow. The regulation of vascular resistance by ECs
      is effected by intracellular Ca(2+) signaling, which leads to production of
      diffusible autacoids (e.g. nitric oxide and arachidonic acid metabolites)(1-3)
      and hyperpolarization(4,5) that elicit smooth muscle cell relaxation. Thus
      understanding the dynamics of endothelial Ca(2+) signaling is a key step towards
      understanding mechanisms governing blood flow control. Isolating endothelial
      tubes eliminates confounding variables associated with blood in the vessel lumen
      and with surrounding smooth muscle cells and perivascular nerves, which otherwise
      influence EC structure and function. Here we present the isolation of endothelial
      tubes from the superior epigastric artery (SEA) using a protocol optimized for
      this vessel. To isolate endothelial tubes from an anesthetized mouse, the SEA is
      ligated in situ to maintain blood within the vessel lumen (to facilitate
      visualizing it during dissection), and the entire sheet of abdominal muscle is
      excised. The SEA is dissected free from surrounding skeletal muscle fibers and
      connective tissue, blood is flushed from the lumen, and mild enzymatic digestion
      is performed to enable removal of adventitia, nerves and smooth muscle cells
      using gentle trituration. These freshly-isolated preparations of intact
      endothelium retain their native morphology, with individual ECs remaining
      functionally coupled to one another, able to transfer chemical and electrical
      signals intercellularly through gap junctions(6,7). In addition to providing new
      insight into calcium signaling and membrane biophysics, these preparations enable
      molecular studies of gene expression and protein localization within native
      microvascular endothelium. 

PMID- 24300897
TI  - PLC-gamma and PI3K link cytokines to ERK activation in hematopoietic cells with
      normal and oncogenic Kras.
AB  - Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active,
      guanosine triphosphate (GTP)-bound conformation and stimulate signaling through
      effector kinases. The presence of the K-Ras(G12D) oncoprotein at a similar
      abundance to that of endogenous wild-type K-Ras results in only minimal
      phosphorylation and activation of the canonical Raf-mitogen-activated or
      extracellular signal-regulated protein kinase kinase (MEK)-extracellular signal
      regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)-Akt-mammalian target
      of rapamycin (mTOR) signaling cascades in primary hematopoietic cells, and these
      pathways remain dependent on growth factors for efficient activation. We showed
      that phospholipase C-gamma (PLC-gamma), PI3K, and their generated second
      messengers link activated cytokine receptors to Ras and ERK signaling in
      differentiated bone marrow cells and in a cell population enriched for leukemia
      stem cells. Cells expressing endogenous oncogenic K-Ras(G12D) remained dependent
      on the second messenger diacylglycerol for the efficient activation of Ras-ERK
      signaling. These data raise the unexpected possibility of therapeutically
      targeting proteins that function upstream of oncogenic Ras in cancer. 

PMID- 24300899
TI  - Age, period and cohort trends in drug abuse hospitalizations within the total
      Swedish population (1975-2010).
AB  - BACKGROUND: The societal consequences of drug abuse (DA) are severe and well
      documented, the World Health Organization recommending tracking of population
      trends for effective policy responses in treatment of DA and delivery of health
      care services. However, to correctly identify possible sources of DA change, one
      must first disentangle three different time-related influences on the need for
      treatment due to DA: age effects, period effects and cohort effects. METHODS: We
      constructed our main Swedish national DA database (spanning four decades) by
      linking healthcare data from the Swedish Hospital Discharge Register to
      individuals, which included hospitalisations in Sweden for 1975-2010. All
      hospitalized DA cases were identified by ICD codes. Our Swedish national sample
      consisted of 3078,129 men and 2921,816 women. We employed a cross-classified
      multilevel logistic regression model to disentangle any net age, period and
      cohort effects on DA hospitalization rates. RESULTS: We found distinct net age,
      period and cohort effects, each influencing the predicted probability of
      hospitalisation for DA in men and women. Peak age for DA in both sexes was 33-35
      years; net period effects showed an increase in hospitalisation for DA from 1996
      to 2001; and in birth cohorts 1968-1974, we saw a considerable reduction (around
      75%) in predicted probability of hospitalisation for DA. CONCLUSIONS: The use of
      hospital admissions could be regarded as a proxy of the population's health
      service use for DA. Our results may thus constitute a basis for effective
      prevention planning, treatment and other appropriate policy responses.

PMID- 24300900
TI  - Association between prescription drug misuse and injection among runaway and
      homeless youth.
AB  - BACKGROUND: The nonmedical use of prescription drugs is the fastest growing drug
      problem in the United States, disproportionately impacting youth. Furthermore,
      the population prevalence of injection drug use among youth is also on the rise.
      This short communication examines the association between current prescription
      drug misuse (PDM) and injection among runaway and homeless youth. METHODS:
      Homeless youth were surveyed between October 2011 and February 2012 at two drop
      in service agencies in Los Angeles, CA. Prevalence ratios (PR) and 95% confidence
      intervals (CI) for the association between current PDM and injection behavior
      were estimated. The outcome of interest was use of a needle to inject any illegal
      drug into the body during the past 30 days. RESULTS: Of 380 homeless youth
      (median age, 21; IQR, 17-25; 72% male), 84 (22%) reported current PDM and 48
      (13%) reported currently injecting. PDM during the past 30 days was associated
      with a 7.7 (95% CI: 4.4, 13.5) fold increase in the risk of injecting during that
      same time. Among those reporting current PDM with concurrent heroin, cocaine, and
      methamphetamine use, the PR with injection was 15.1 (95% CI: 8.5, 26.8).
      CONCLUSIONS: Runaway and homeless youth are at increased risk for a myriad of
      negative outcomes. Our preliminary findings are among the first to show the
      strong association between current PDM and injection in this population. Our
      findings provide the basis for additional research to delineate specific patterns
      of PDM and factors that enable or inhibit transition to injection among homeless
      and runaway youth.

PMID- 24300902
TI  - Inherited cancer syndromes and the thyroid: an update.
AB  - PURPOSE OF REVIEW: Knowledge related to hereditary thyroid cancer syndromes has
      expanded enormously. This review identifies contributions that have changed
      approaches to diagnosis and broadened treatment options for patients with
      hereditary medullary and nonmedullary thyroid cancers related to multiple
      endocrine neoplasia type 2 (MEN2), Cowden syndrome, and familial adenomatous
      polyposis (FAP). RECENT FINDINGS: A new risk-stratification scheme based on type
      of RET gene mutation informs the age at which prophylactic thyroidectomy and
      diagnostic screening for MEN-associated endocrine diseases should occur. Two new
      US Food and Drug Administration-approved targeted medical therapies are now
      available for medullary thyroid cancer. There is better understanding of more
      aggressive clinical features and increased lifetime cancer risks for patients
      with well differentiated thyroid cancers as part of families with and without
      Cowden syndrome or FAP. This has led to a clearer appreciation for the role and
      timing of thyroid ultrasound screening in these populations. It has also informed
      the appropriate extent of thyroid surgery and the circumstances in which
      prophylactic thyroidectomy is reasonable to consider as part of hereditary
      syndromes other than MEN2. SUMMARY: Recognition and early diagnosis of these
      syndromes allows for comprehensive medical care and may improve thyroid cancer
      related outcomes. Ultrasound-based screening programs to detect thyroid disease
      are advised for patients and family members with hereditary cancer syndromes.

PMID- 24300901
TI  - Objective and perceived neighborhood characteristics and tobacco use among young
      adults.
AB  - BACKGROUND: In the US, past month tobacco use is higher among young adults aged
      18-25 years than among any other age group. Neighborhood disorder may be a
      malleable environmental determinant of tobacco use among young adults; its
      correlation with tobacco use is understudied. The purpose of this study is to
      examine whether perceived and objectively measured neighborhood factors are
      associated with tobacco use among young adults in Baltimore City. METHODS: This
      cross-sectional study of predominately African American young adults (n=359) used
      logistic regression models via generalized estimating equations (GEE) to estimate
      the association of perceived and objective neighborhood disorder with past month
      tobacco use, adjusting for race, age, sex, income, and other substance use. Two
      measures of perceived neighborhood environment - neighborhood drug involvement,
      and neighborhood social cohesion - were derived from the Neighborhood Environment
      Scale (NES). Objective neighborhood disorder was measured via trained field
      raters using the Neighborhood Inventory for Environmental Typology (NIfETy)
      instrument. RESULTS: Sex modified the relationship between perceived neighborhood
      drug involvement and past month tobacco use, and the association was significant
      among women only (aOR=1.49; 95% CI=1.19-1.88). Perceptions of neighborhood social
      cohesion (aOR=0.97; 95% CI=0.83-1.13), and objective neighborhood disorder
      (aOR=1.17; 95% CI=0.98-1.38) were not significantly associated with past month
      tobacco use. CONCLUSION: Understanding the correlation between perceived and
      objective neighborhood disorder, and their independent association with tobacco
      use can potentially lead to environmentally based interventions aimed at reducing
      tobacco use among young adults who live in urban environments.

PMID- 24300904
TI  - Under-reporting remains a key limitation of self-reported dietary intake: an
      analysis of the 2008/09 New Zealand Adult Nutrition Survey.
AB  - BACKGROUND/OBJECTIVES: The most recent New Zealand Adult Nutrition Survey 2008/09
      (ANS 08/9) revealed a decrease in reported energy intakes (EIs) compared with the
      previous 1997 National Nutrition Survey (NNS97). Conversely, measured body
      weights increased over the same period. We conducted an analysis on the ANS 08/9
      data sets to evaluate reported EIs. SUBJECTS/METHODS: Analysis was conducted on
      data from 3919 (1715 men and 2204 women aged > or = 15 years) survey participants
      who completed the 24-h dietary recall in the ANS 08/9. Under-reporting was
      assessed using the ratio of reported EI to estimated resting metabolic rate
      (EI:RMRest), and a cutoff limit of <0.9 (EI:RMRest) was used to identify low
      energy reporters (LERs). Results were examined by gender, body size, age and
      ethnicity. RESULTS: The mean EI:RMRest (s.e.m.) was 1.34 (0.02) for men, and 1.23
      (0.02) for women. Overall, 21% of men and 25% of women were classified as LERs.
      There was a greater prevalence of LERs among people with overweight (25%), or
      obesity (30%) than people with normal body weight (16%, P<0.001). The oldest age
      group (> or =65 years) had a greater prevalence of LERs (33%) compared with all
      other age groups (19-24%, P<0.001). Pacific people had a greater prevalence of
      LERs (33%) compared with Maori (26%, P=0.007) and European (23%, P<0.001).
      Compared with the NNS97, a substantial increase in the prevalence of LERs was
      evident in most subgroups. CONCLUSIONS: Under-reporting of EI will continue to be
      a major limitation of nutrition surveys without technological innovation. Care
      should be taken when interpreting EI data.

PMID- 24300905
TI  - The possible influence of sleep in childhood obesity.

PMID- 24300906
TI  - Body composition and body fat distribution are related to cardiac autonomic
      control in non-alcoholic fatty liver disease patients.
AB  - BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control
      marker, was shown to be related to body composition (BC), yet this was not tested
      in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was
      to determine if, and to what extent, markers of BC and body fat (BF) distribution
      are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC
      was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men,
      51+/-13 years, and 9 women, 47+/-13 years). BF depots ratios were calculated to
      assess BF distribution. Subjects' HRR was recorded 1 (HRR1) and 2 min (HRR2)
      immediately after a maximum graded exercise test. RESULTS: BC and BF distribution
      were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular
      BF ratio showed a negative relation with HRR1 (r=-0.613, r=-0.597 and r=-0.547,
      respectively, P<0.01) and HRR2 (r=-0.484, r=-0.446, P<0.05, and r=-0.590, P<0.01,
      respectively). Age seems to be related to both HRR1 and HRR2 except when
      controlled for BF distribution. The preferred model in multiple regression should
      include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2=0.549;
      P<0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2=0.430;
      P<0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD
      patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of
      HRR and therefore may be best related to cardiovascular increased risk, and
      possibly act as a mediator in age-related cardiac autonomic control variation.

PMID- 24300907
TI  - Coffee consumption and risk of prostate cancer: an up-to-date meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Epidemiologic findings concerning the association between
      coffee consumption and prostate cancer risk yielded mixed results. We aimed to
      investigate the association by performing a meta-analysis of all available
      studies. SUBJECTS/METHODS: We searched PubMed, Web of Science and EMBASE for
      studies published up to July 2013. We calculated the summary relative risk (RR)
      and 95% confidence intervals (CIs) for ever, moderate and highest consumption of
      coffee vs non/lowest consumption. The dose-response relationship was assessed by
      restricted cubic spline model and multivariate random-effect meta-regression.
      RESULTS: A total of 12 case-control studies and 12 cohort studies with 42,179
      cases were selected for final meta-analysis. No significant associations were
      found among overall analysis. A borderline positive association was found for
      highest drinkers in five small hospital-based case-control (HCC) studies
      involving 2278 cases. However, compared with non/lowest drinkers, the summary RRs
      were 0.92 (95% CI=0.85-0.99) for ever drinkers, 0.92 (95% CI=0.85-1.00) for
      moderate drinkers and 0.83 (95% CI=0.72-0.96) for highest drinkers from 12 cohort
      studies, comprising a total of 34,424 cases. An increase in coffee intake of two
      cups/day was associated with a 7% decreased risk of prostate cancer according to
      cohort studies. A significant inverse relationship was also found for fatal
      prostate cancers and high-grade prostate cancers. CONCLUSIONS: Case-control
      studies especially HCC ones might be prone to selection bias and recall bias that
      might have contributed to the conflicting results. Therefore, the present meta
      analysis suggests a borderline significant inverse association between coffee
      consumption and prostate cancer risk based on cohort studies.

PMID- 24300908
TI  - Long-term effects of enteral feeding on growth and mental health in adolescents
      with anorexia nervosa--results of a retrospective German cohort study.
AB  - BACKGROUND/OBJECTIVE: Anorexia nervosa (AN) is a severe eating disorder with a
      high mortality rate. Treatment regimes show regional and global variation and are
      sometimes supported by enteral feeding (EF) via nasogastric tube, although risks
      and benefits are still unclear. We aimed to find out whether EF improves growth
      and AN recovery and prevents psychiatric comorbidities. SUBJECTS/METHODS: Data
      were retrospectively collected from medical records and follow-up data were
      collected via questionnaires. Two hundred and eight female AN patients who were
      hospitalized below the age of 18 years with a mean follow-up of 6 years were
      analyzed. We calculated relative risks for the association between EF and
      suboptimal growth, remission of AN and the occurrence of psychiatric
      comorbidities, adjusting for potential confounders. RESULTS: A third of the
      analyzed girls received EF at any time. In the adjusted analyses, we found no
      significant associations between EF and suboptimal growth, the persistence of AN
      and the occurrence of psychiatric comorbidities, respectively. CONCLUSION: Our
      data suggest EF to be neither a risk factor nor beneficial for growth, recovery
      or persistence of AN and the occurrence of psychiatric comorbidities.

PMID- 24300909
TI  - Response to Dr. Andersen et al.

PMID- 24300910
TI  - Soft drink consumption and unhealthy diet.

PMID- 24300911
TI  - Relationship between socioeconomic status and anemia prevalence in adolescent
      girls based on the fourth and fifth Korea National Health and Nutrition
      Examination Surveys.
AB  - BACKGROUND/OBJECTIVES: We studied the relationship between socioeconomic status
      (SES), represented by household income, and the prevalence of anemia and iron
      deficiency anemia (IDA) among adolescent girls in Korea. SUBJECTS/METHODS: The
      samples were based on the data from a four-year (2008-2011) collection for the
      Korea National Health and Nutrition Examination Survey (1312 girls, age 10-18
      years). The survey included demographic, anthropometric, biochemical and
      nutritional parameters. A multiple regression analysis after adjusting for age,
      body mass index (BMI), red blood cell count, white blood cell count and red meat
      intake was performed. Anemia was defined as hemoglobin level lower than 11.5 g/dl
      for ages 10-11 years and 12.0 g/dl for ages 12-14 years. Iron deficiency was
      defined as serum ferritin level below 15 MUg/l. RESULTS: The prevalences of
      anemia and IDA in Korean girls were 5.3 and 4.2%, respectively. Girls with anemia
      were older, taller, weighed more, had higher BMI, had higher portion of menarche
      experience and consumed less red meat than girls without anemia. Girls with
      higher income had lower anemia prevalence and consumed more iron and vitamins.
      Logistic regression analysis showed a decreasing trend in anemia prevalence as
      household income increased. Correlation analysis demonstrated that there is a
      relationship between household income and serum hemoglobin and ferritin levels
      (P=0.003 and P=0.026, respectively). CONCLUSIONS: Higher SES leads to lower
      prevalence of anemia and IDA in Korean adolescent girls. This may be due to the
      fact that higher SES individuals consume more iron and vitamin C.

PMID- 24300912
TI  - MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in
      mice.
AB  - MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs
      and inhibit translation or promote mRNA degradation. Recent reports have
      indicated that miR-33, which is located within the intron of sterol regulatory
      element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a
      potential therapeutic target for the treatment of atherosclerosis. Here we show
      that deletion of miR-33 results in marked worsening of high-fat diet-induced
      obesity and liver steatosis. Using miR-33(-/-)Srebf1(+/-) mice, we demonstrate
      that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and
      liver steatosis in miR-33(-/-) mice involve enhanced expression of SREBP-1. These
      results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR
      33 in vivo. 

PMID- 24300914
TI  - Trastuzumab and oxaliplatin exhibit a synergistic antitumor effect in HER2
      postive gastric cancer cells.
AB  - Trastuzumab has recently been recommended for the treatment of epidermal growth
      factor receptor-2 (HER2)-positive advanced gastric cancer in combination with the
      capecitabine/cisplatin (XP) versus continuous infusion of 5
      fluorouracil/cisplatin (FP) regimen. However, it is unclear whether it is
      rational to combine trastuzumab with other chemotherapy regimens in clinical
      practice. Our study demonstrates that adding trastuzumab to oxaliplatin, a
      commonly used third-generation platinum derivative, increases the antitumor
      effect in vitro. In MTT assays, combination treatment with oxaliplatin and
      trastuzumab significantly decreased the concentration of oxaliplatin required to
      induce 50% growth inhibition in HER2-positive gastric cancer cells. Further
      investigation revealed that the trastuzumab-oxaliplatin combination induced cell
      cycle arrest and decreased expression of both p-AKT and p-ERK. Notably, this
      treatment combination induced downregulation of the excision repair cross
      complementation group 1 (ERCC1) protein, which is involved in the key repair
      process of the oxaliplatin-DNA platinum adduct at the protein level. Similar
      changes were also observed in HER2-positive breast cancer cells. These findings
      suggest that trastuzumab synergizes the cytotoxic effect of oxaliplatin on HER2
      positive gastric and breast cancer cells. Our study provides preclinical evidence
      for the optimization of this combination regimen in the treatment of HER2
      positive gastric cancer patients. 

PMID- 24300915
TI  - Bortezomib and IL-12 produce synergetic anti-multiple myeloma effects with
      reduced toxicity to natural killer cells.
AB  - The aim of this study was to examine the hypothesis that a combination of
      proteasome inhibition by bortezomib and immune therapy with interleukin-12 (IL
      12) can produce enhanced antitumor efficacy relative to the effects of either of
      these agents alone. A mouse xenograft model of myeloma was developed. The mice
      were randomly divided into saline control (NS), IL-12 (0.4 ug/animal;
      intraperitoneal), bortezomib (0.75 mg/kg; intravenous), and bortezomib+IL-12
      groups. Effects of treatments on tumor growth were assessed by before and after
      treatment comparisons and group comparisons. The effects of various treatments on
      the number of peripheral blood lymphocytes and natural killer (NK) cells were
      assessed by complete blood count and flow cytometry analysis. The cell-killing
      function of NK cells in splenocytes was evaluated using the lactate dehydrogenase
      release assay. IL-12 treatment alone produced a mild decrease in tumor volume
      compared with control (P>0.05). Bortezomib alone resulted in substantial
      inhibition of tumor growth at varying time points, reaching ~65 and ~60%
      reduction in tumor volume after 15 and 21 days of therapy, respectively. At the
      same time points, the combination therapy produced ~75 and ~84% decreases in
      tumor growth, respectively, which were significantly greater than the reduction
      produced by bortezomib monotherapy. Tumors resumed growth upon termination of
      bortezomib treatment at 2 weeks, although the tumor volume was still
      significantly smaller than that in the time-matched NS and IL-12 animals. This
      rebound of tumor growth was completely prevented with the combination therapy,
      and tumor volume continued to decrease throughout the time course. The percentage
      and total number of NK cells were significantly decreased after bortezomib
      monotherapy and combination therapy; however, they remained unaltered after IL-12
      treatment compared with no treatment. Further, combination therapy significantly
      restored the bortezomib-induced functional impairment of the cell-killing
      capability of NK cells, relative to bortezomib alone. We conclude that the
      bortezomib-IL-12 combination therapy offers superior antitumor efficacy over
      monotherapy with either bortezomib or IL-12 in a mouse model of myeloma.
      Restoration of bortezomib-induced functional impairment of NK cells by IL-12 may
      be a mechanism for the synergetic effects of the two agents. Therefore, a
      combination of the two agents may represent a more rational therapeutic approach
      for myeloma.

PMID- 24300916
TI  - Taxanes in combination with biologic agents for ovarian and breast cancers.
AB  - Taxane-based cytotoxic therapy is commonly prescribed for breast and ovarian
      cancers. Although these cancers are often sensitive to such therapy, clinical
      benefit and overall survival are limited owing to the development of
      chemoresistance and recurrence. Biologic agents that specifically target proteins
      of growth factor signaling pathways, which are hyperactivated in cancers, offer
      attractive targets for cancer therapeutics and may work synergistically with
      standard taxane-based chemotherapy to improve patient outcomes. We review
      clinical trials of biologic agents--angiogenic, tyrosine kinase, and antibody
      inhibitors--in combination with taxane-based therapy for ovarian and breast
      cancers. Many clinical trials have shown promising results. However, some
      biologic agents still need larger trials to assess safety and efficacy. As
      research into the heterogeneity and complexity of ovarian and breast cancers
      improves our understanding of the molecular pathways involved, there is no
      question that targeted therapies with biologic agents will expand the future
      array of available cancer therapeutics.

PMID- 24300913
TI  - Taxanes: their impact on gynecologic malignancy.
AB  - The use of taxanes in the treatment of gynecologic malignancies has expanded
      tremendously over the past 30 years. Both paclitaxel and docetaxel have unique
      microtubule stabilizing, antiangiogenic and radiation sensitizing properties that
      endow them with remarkable activity as chemotherapeutic agents. As research into
      the appropriate dose, timing, treatment interval, and response rates have been
      studied, they have emerged as one of the most active agents available in the
      treatment of gynecologic cancer. The body of research on taxanes continues to
      expand especially with regard to the use of taxanes in alternative formulations
      and in combination with newer treatments or routes of treatment. This review
      focuses on the development of taxanes as an effective therapy in the treatment of
      gynecologic cancers and data currently available in the literature regarding
      their efficacy. Future directions of taxane-based chemotherapy with regards to
      ovarian, uterine, and cervical cancers are also addressed. There is little doubt
      that taxane-based chemotherapy will remain an integral part of the treatment of
      gynecologic cancer for the foreseeable future. 

PMID- 24300917
TI  - Clinical features of taxane neuropathy.
AB  - Sensory neuropathy is the dose-limiting toxicity of paclitaxel and also impacts
      on the use of docetaxel and other taxanes. The cause of this adverse effect has
      to do with their mechanism of action against microtubules and its interaction
      with neuronal cytoskeletal components. The variability of this toxicity is
      defined by several factors including disease type, taxane class, schedule and
      dose of the specific drug, patient demographics, and use of taxanes in
      combination regimens (especially with the platinums that are also neurotoxic).
      Prevention of life-long neuropathy is only produced if the causative drug is
      halted--treatments to reverse toxicity have shown only minimal improvement. This
      review investigates trials defining the clinical factors that determine the
      therapeutic window of taxanes and the enhanced susceptibility to this toxicity.
      In addition, case vignettes illustrate the range of clinical manifestations of
      this toxicity during taxane administration.

PMID- 24300918
TI  - New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl
      diphosphate synthase.
AB  - As part of our project pointed at the search of new antiparasitic agents against
      American trypanosomiasis (Chagas disease) and toxoplasmosis a series of 2
      alkylaminoethyl-1-hydroxy-1,1-bisphosphonic acids has been designed, synthesized
      and biologically evaluated against the etiologic agents of these parasitic
      diseases, Trypanosoma cruzi and Toxoplasma gondii, respectively, and also towards
      their target enzymes, T. cruzi and T. gondii farnesyl pyrophosphate synthase
      (FPPS), respectively. Surprisingly, while most pharmacologically active
      bisphosphonates have a hydroxyl group at the C-1 position, the additional
      presence of an amino group at C-3 resulted in decreased activity towards either
      T. cruzi cells or TcFPPS. Density functional theory calculations justify this
      unexpected behavior. Although these compounds were devoid of activity against T.
      cruzi cells and TcFPPS, they were efficient growth inhibitors of tachyzoites of
      T. gondii. This activity was associated with a potent inhibition of the enzymatic
      activity of TgFPPS. Compound 28 arises as a main example of this family of
      compounds exhibiting an ED50 value of 4.7 MUM against tachyzoites of T. gondii
      and an IC50 of 0.051 MUM against TgFPPS.

PMID- 24300919
TI  - Combining the tail and the ring approaches for obtaining potent and isoform
      selective carbonic anhydrase inhibitors: solution and X-ray crystallographic
      studies.
AB  - 5-(3-Tosylureido)pyridine-2-sulfonamide and 4-tosylureido-benzenesulfonamide (ts
      SA) only differ by the substitution of a CH by a nitrogen atom, but they have
      very different inhibitory properties against the metalloenzyme carbonic anhydrase
      (CA, EC 4.2.1.1). By means of X-ray crystallography on the human CA II adducts of
      the two compounds these differences have been rationalized. As all sulfonamides,
      the two compounds bind in deprotonated form to the Zn(II) ion from the enzyme
      active site and their organic scaffolds extend throughout the cavity,
      participating in many interactions with amino acid residues and water molecules.
      However the pyridine derivative undergoes a tilt of the heterocyclic ring
      compared to the benzene analog, which leads to a very different orientation of
      the two scaffolds when bound to the enzyme. This tilt also leads to a clash
      between a carbon atom from the pyridine ring of the first inhibitor and the OH
      moiety of Thr200, leading to less effective inhibitory properties of the pyridine
      versus the benzene sulfonamide derivative. Indeed, ts-SA is a promiscuous, low
      nanomolar inhibitor of 7 out of 10 human (h) CA isoforms, whereas the pyridine
      sulfonamide is a low nanomolar inhibitor only of the tumor-associated hCA IX and
      XII, being less effective against other 9 isoforms. Thus, a difference of one
      atom (N vs CH) in two isostructural sulfonamides leads to drastic differences of
      activity, phenomenon understood at the atomic level through the high resolution
      crystallographic structure and kinetic measurements reported in the paper.
      Combining the tail and the ring approaches in the same chemotype leads to isoform
      selective, highly effective sulfonamide CA inhibitors. 

PMID- 24300920
TI  - Synthesis and biological evaluation of farnesylthiosalicylamides as potential
      anti-tumor agents.
AB  - Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were
      synthesized and biologically evaluated. It was found that FTS-monoamide molecules
      (10a-g) displayed strong anti-proliferative activity against seven human cancer
      cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amide
      10f was the most active, with IC50s of 3.78-7.63 MUM against all tested cancer
      cells, even more potent than sorafenib (9.12-22.9 MUM). In addition, 10f induced
      SMMC-7721 cell apoptosis, down-regulated the expression of Bcl-2 and up-regulated
      Bax and caspase-3. Furthermore, 10f had the improved aqueous solubility relative
      to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related
      signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising
      candidate for the intervention of human cancers.

PMID- 24300921
TI  - Novel metabolic surgery for type II diabetes mellitus: loop duodenojejunal bypass
      with sleeve gastrectomy.
AB  - A total of 22 (14F/8M) patients with a mean age of 50.3 years (range, 33 to 64 y)
      and a mean body mass index of 28.4 kg/m (range, 21.8 to 38.3 kg/m) underwent loop
      duodenojejunal bypass with sleeve gastrectomy from October 2011 to March 2012.
      The mean duration of onset of type 2 diabetes mellitus was 8 years (range, 1 to
      20 y). All patients were on oral hypoglycemic agents; 3 (14%) patients were also
      using insulin. The mean preoperative glycosylated hemoglobin (HbA1c), fasting
      plasma sugar, and C-peptide levels dropped from 8.6% (range, 7% to 13.2%), 147
      mg/dL (range, 108 to 241 mg/dL), and 2.4 ng/mL (range, 0.7 to 4.1 ng/mL) to 6.2%
      (range, 5.1% to 9.1%), 110 mg/dL (range, 72 to 234 mg/dL), and 1.3 ng/mL (range,
      0.6 to 2.8 ng/mL) at 6 months, respectively. At 6 months, 11 (50%) patients
      showed type 2 diabetes mellitus remission (HbA1c<6.0%), and 20 (91%) patients
      achieved HbA1c<7.0% without medicine. There were no intraoperative or early
      postoperative complications. Loop duodenojejunal bypass with sleeve gastrectomy
      is safe, feasible, and shows good efficacy in terms of glycemic control in this
      preliminary report with short follow-up. 

PMID- 24300922
TI  - Laparoscopic central pancreatectomy: a review of 51 cases.
AB  - BACKGROUND: Central pancreatectomy is an alternative technique for benign or low
      grade malignant tumors. Laparoscopic central pancreatectomy has been rarely
      performed, with only 48 cases reported in the English literature. The aim of this
      paper was to review all published cases together with 3 cases from our
      institution. METHODS: All published articles indexed on PubMed were included.
      Terms used were "laparoscopic central pancreatectomy" or "laparoscopic middle
      pancreatectomy." Variables studied were the operative time, the type of
      reconstruction, indications, the use of robotic or hand assistance, blood loss,
      transfusion, pancreatic fistula, hospital stay, follow-up, development of
      exocrine and/or endocrine insufficiency, morbidity, and mortality. RESULTS: A
      total of 51 patients were identified. Twenty-one patients underwent total
      laparoscopy (41.2%), 27 required robotic assistance (52.9%), one required hand
      assistance (1.9%), and there were 2 conversions. In 18 cases (35.3%), pancreatic
      reconstruction involved a Roux-en-Y pancreatojejunostomy, and in 32 cases,
      pancreatogastrostomy (62.7%). The mean operative time was 356 minutes. Blood loss
      was minimal in most cases, and only 1 patient required blood transfusion (1.9%).
      Mortality was nil, but morbidity was high, mainly because of pancreatic fistula
      (46%). The mean hospital stay was 13.8 days. All patients underwent laparoscopic
      central pancreatectomy for benign or low-grade neoplasms. The mean follow-up
      duration was 19.6 months (range, 2 to 48 mo). No patient presented exocrine or
      endocrine insufficiency. CONCLUSIONS: Laparoscopic central pancreatectomy is a
      feasible and useful technique for the removal of tumors located in the neck of
      the pancreas. There are very few centers performing this operation, and
      therefore, a literature review was necessary to identify its indications and
      technical possibilities, and to promote its use.

PMID- 24300923
TI  - Therapeutic effect of low-molecular weight heparin and incidence of lower limb
      deep venous thrombosis and pulmonary embolism after laparoscopic bariatric
      surgery.
AB  - BACKGROUND: The aim of our study was to determine the therapeutic effect of low
      molecular weight heparin after laparoscopic Roux-en-Y gastric bypass. METHODS: We
      prospectively analyzed data of 39 patients who underwent Roux-en-Y gastric bypass
      from 1093 consecutive patients who underwent bariatric procedures from May 1999
      to May 2012. All patients were given 40 mg enoxaparin subcutaneously once daily
      preoperatively and continued for 5 days. RESULTS: There were 31 females. Mean age
      was 32.48 years and mean body mass index was 44.59 kg/m. Only 46.1% of patients
      reached the defined therapeutic dose on the second day and 41% on the fifth day.
      One fatal pulmonary embolism was recorded (1/1093, 0.09%) in the entire series.
      CONCLUSIONS: Anti-Xa surveillance did not correlate strongly with outcome.
      Further studies are required for proper dose adjustments of low-molecular weight
      heparin in these obese patients and whether anti-Xa monitoring should be
      continued.

PMID- 24300924
TI  - Single-incision laparoscopic surgery for colon and rectal cancer: an initial
      experience with the technique.
AB  - BACKGROUND: Single-incision laparoscopic surgery seems destined to take its place
      in the evolution of minimally invasive surgery. Although isolated cases have been
      reported in the literature, no series has yet been published on the use of this
      approach to treat colorectal cancer. We describe the surgical technique and
      perioperative outcomes of this approach in 15 patients diagnosed for colorectal
      cancer. METHODS: We have used several devices to gain transumbilical access to
      the abdominal cavity, usually working with 3 cannulae to insert the instruments.
      We used a 5 mm endograsper, and articulated rotating (roticulating) endoscissors
      and endodissector to assist dissection. Vascular control and section of the
      rectum were performed using roticulating endostaplers. We combined the use of
      curved and straight instruments as required for each step during surgery. The
      dissection technique performed was the same as the one we normally use in
      conventional laparoscopy. Specimens were extracted through the umbilical
      incision. RESULTS: The most commonly performed procedure was sigmoidectomy (n=7),
      followed by high anterior resection of the rectum (n=5). The mean surgical time
      was 185+/-44.9 minutes. The mean hospital stay was 6.2+/-4.7 days. Three cases
      (20%) were converted to conventional laparoscopy. Surgery was curative in all of
      the patients. CONCLUSIONS: Single-access transumbilical laparoscopic surgery is
      feasible and safe for treating colorectal carcinoma when performed by surgeons
      with ample experience in laparoscopic colorectal resection. Further studies are
      needed to determine the advantages and drawbacks of this procedure.

PMID- 24300925
TI  - More adequate lymph node dissection after laparoscopic colorectal surgery.
AB  - The aim of this study was to determine whether there is a difference in the
      amount of lymph nodes harvested during open and laparoscopic surgery and whether
      this might influence the subsequent offering of adjuvant chemotherapy. All
      patients who underwent colorectal surgery for colorectal malignancies from July
      2006 to April 2008 were included in our prospective database and in the study. In
      the laparoscopic group, 11/55 (20%) patients with stage II tumors had <10 lymph
      nodes in the pathology specimen when compared with 44/110 (40%) in the open group
      (P=0.01). The average number of lymph nodes was 12.1 for laparoscopic as compared
      with 10.2 lymph nodes for open resection (P=0.009). We demonstrate a significant
      increase in the number of resected lymph nodes with laparoscopic surgery.
      Significantly more patients in the open surgery group had <10 negative lymph
      nodes and were subsequently offered chemotherapy for their high-risk stage II
      colorectal malignancies. 

PMID- 24300926
TI  - A laparoscopic approach to CBD stones.
AB  - AIM: : This study aimed to evaluate single-stage surgical (laparoscopic or open)
      approach to the management of common bile duct (CBD) stones, as treatment of
      choice. METHODS: Prospectively collected data to assess outcomes of CBD
      clearance, morbidity, mortality, and hospital stay, and compared with published
      data. RESULTS: Successful clearance of CBD stones was achieved in 96% cases,
      laparoscopic exploration successful in 83%. Retained stones were found in 4%
      cases and another 5% developed postoperative complications. Common length of stay
      in hospital was 2 days, although mean stay was 4 days. Seventy-three percent of
      cases were elective, 27% were emergencies. Conversion rate to open surgery was
      14%, which was mainly in emergency cases. Postoperative mortality was 1.2%, not
      directly related to the procedure. CONCLUSIONS: Good outcomes can be achieved,
      comparing favorably with those of other modalities, when laparoscopic bile duct
      exploration is chosen as treatment for CBD stones; the best results can be
      anticipated in elective patients.

PMID- 24300927
TI  - Laparoscopy in blunt and penetrating abdominal trauma.
AB  - The objective of our study was to assess the abilities and limitations of
      laparoscopy and evaluate its role in examination and treatment of patients with
      abdominal trauma. A total of 628 patients with blunt and penetrating abdominal
      trauma were included in this retrospective 12-year survey (2000 to 2011). All
      patients in the study underwent either laparotomy (280 patients) or urgent
      laparoscopy (348 patients). There was no difference in the demographic data and
      trauma severity between the 2 groups. Conversion to open surgery was performed in
      130 cases (37.3%). Diagnostic laparoscopy without therapeutic manipulations was
      used in 160 patients (46%) and therapeutic laparoscopy was carried out in 58
      patients (16.7%). Quicker recovery time, less pain, shorter hospital stay, and
      lower complication rate were observed in patients after laparoscopic surgery
      compared with patients after open surgery. No missed abdominal organs injuries
      were revealed after laparoscopic examination of abdominal cavity. 

PMID- 24300928
TI  - Laparoscopic peritoneal dialysis catheter implantation with an intra-abdominal
      fixation technique: a report of 53 cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility, the safety,
      and outcomes of renal replacement therapy with the laparoscopic technique for
      peritoneal dialysis (PD) catheter implantation with an intra-abdominal fixation.
      METHODS: Medical records of 53 patients with end-stage renal disease who
      underwent laparoscopic PD catheter implantation with an intra-abdominal fixation
      in our department from December 2008 to October 2009 were reviewed
      retrospectively. Their surgical procedure, operative outcomes, postoperative
      complications, and follow-up outcomes were analyzed. RESULTS: All patients
      underwent laparoscopic PD catheter implantation with an intra-abdominal fixation
      successfully. Neither conversion to open surgery nor major intraoperative
      complications were observed. The median operative time was 24.2+/-10.5 minutes.
      The operative cost was 837.3+/-107.0 US$. Two patients (3.8%) had catheter
      obstruction peritonitis 12 and 15 months after surgery, respectively, and both of
      them had the catheter removed. CONCLUSIONS: Laparoscopic PD catheter implantation
      with an intra-abdominal fixation of the catheter tip is feasible and safe. It had
      a low incidence of PD catheter migration and other PD-related postoperative
      complications with the benefit of minimal invasiveness, a shorter operation time,
      and quicker postoperative recovery.

PMID- 24300929
TI  - Laparoscopic colectomy for obstructive colorectal carcinoma.
AB  - Laparoscopic surgery for obstructive colorectal carcinoma is a controversial
      issue. Defining the obstructive carcinoma as colonoscopic impassability, the
      patients with obstructive carcinoma were managed according to the treatment
      algorithm, by which the indication of open or laparoscopic surgery was
      determined. As a result, 31 patients with obstructive colorectal carcinoma
      underwent laparoscopic surgery. The location of the tumor was in the right side
      in 10 patients and in the left in 21 patients. Preoperatively, all cases were
      managed by restriction of oral intake and/or decompression. Laparoscopic surgery
      was completed in 26 cases and colonic obstruction was the direct cause of the
      conversion in only 1 case. Regarding postoperative complications, there were 3
      surgical site infections and 3 instances of postoperative prolonged ileus but no
      mortality. Oncologically, the primary tumor was completely resected in each case
      and lymph node harvest (26.6) was adequate. 

PMID- 24300930
TI  - A critical appraisal of laparoscopic pancreatic enucleations: right-sided
      procedures (Pancreatic Head, Uncus) are not mini-invasive surgery.
AB  - Laparoscopic pancreatic enucleation is increasingly performed worldwide. Few
      small-sized series show encouraging results, especially after enucleations
      performed for lesions located in the left part of the pancreas. The outcome of
      laparoscopic pancreatic enucleations was retrospectively evaluated by the
      analysis of prospectively collected parameters. Results of right-sided
      (head/uncus) and left-sided (neck/body/tail) enucleations were compared. From
      1997 to 2010, 25 patients underwent laparoscopic pancreatic enucleation. The
      conversion rate was 12%, mean operating time was 158 minutes, and mean blood loss
      was 106 mL. Morbidity was 56% and the rate of pancreatic fistula 32%. Outcome
      differed between patients undergoing right-sided and left-sided enucleations, the
      operative time being 178 versus 132 minutes, morbidity 64% versus 45%, and median
      hospital stay 26 versus 9 days, respectively. Pancreatic enucleation is feasible
      by laparoscopy, with a high success rate and no mortality but significant
      morbidity. Laparoscopy seems to be of no use in right-sided procedures.
      Pancreatic fistula is still the main cause of long-lasting morbidity. 

PMID- 24300931
TI  - Laparoscopic resection for colorectal cancer improves short-term outcomes in very
      elderly colorectal cancer patients.
AB  - BACKGROUND: Laparoscopic-assisted colectomy (LAC) for colorectal cancer has been
      shown to improve short-term outcomes compared with open colectomy (OC) in
      colorectal cancer patients. However, there are a few reports that describe the
      efficacy of LAC in the very elderly population. We investigated whether LAC
      improves short-term outcomes in elderly patients, especially those 80 years of
      age or older. METHOD: Eighty-two consecutive elderly (80 years of age or older)
      patients who underwent either OC or LAC for colorectal cancer were reviewed.
      Continuous variables were analyzed by the Mann-Whitney U test. Categorical
      variables were compared by chi tests. RESULTS: Of the 82 elderly patients with
      colorectal cancer, 34 patients underwent OC and 48 patients had LAC. There were
      no significant differences in postoperative complications between the 2 groups.
      LAC demonstrated less blood loss, fewer days on a liquid diet, and a shorter
      postoperative stay in the hospital than OC. CONCLUSIONS: LAC improved short-term
      outcomes even in very elderly patients.

PMID- 24300932
TI  - Three-dimensional computed tomography for analyzing the vascular anatomy in
      laparoscopic surgery for right-sided colon cancer.
AB  - BACKGROUND: The mesenteric vessels have many branching patterns. This study
      clarified the anatomic relationship between the superior mesenteric vein (SMV),
      the right colic artery (RCA), and the ileocolic artery (ICA) using 3-dimensional
      computed tomography (3D-CT). The relationship between the RCA and the right colic
      vein (RCV) was also examined. METHODS: Between April 2006 and July 2011, all
      patients with colorectal cancer underwent multidetector computed tomography
      (MDCT) before laparoscopic surgery. The 100 most recent consecutive cases were
      analyzed. 3D-CT images were made by combining arterial angiography, venous
      angiography, colonography, tumor, lymph node, and duodenal images. RESULTS: The
      RCA branched from the SMA in 37 cases (37%); of these, 21 had an ICA that crossed
      anterior to the SMV and 16 had an ICA that crossed posterior. When the ICA
      crossed anterior to the SMV, all had an RCA that crossed anterior to the SMV, and
      no posterior RCA was seen. Furthermore, the RCV joined the SMV in 10 cases (27%)
      and the gastrocolic trunk in 27 cases (73%). CONCLUSIONS: Our study clarified the
      anatomic variety of the vessels in right-sided colon cancer. Preoperative 3D-CT
      is useful for understanding the anatomy to ensure a safe, precise operation.

PMID- 24300933
TI  - Diagnostic flexible laparoscopy: a single incision procedure.
AB  - A novel, minimally invasive diagnostic laparoscopy procedure is described in this
      report. After positioning a percutaneous trocar and inducing CO2
      pneumoperitoneum, a flexible endoscope is introduced through the trocar to
      inspect intra-abdominal organs, including the surface of the liver, the
      gallbladder, the stomach, the intestine, the pelvic organs, and free
      intraperitoneal fluid. Simple procedures such as gathering histological or
      cytological samples, intraperitoneal lavage, collecting peritoneal fluid for
      culture, removing adhesions and cyst puncturing are carried out at the endoscopic
      surgeon's discretion through 1 or 2 working channels. Only a single incision is
      necessary and, unlike Natural Orifice Translumenal Endoscopic Surgery, visceral
      iatrogenic perforations are unnecessary. 

PMID- 24300934
TI  - Reconstruction of esophagojejunostomies using endoscopic linear staplers in
      totally laparoscopic total gastrectomy: report of 139 cases in a large-volume
      center.
AB  - Totally laparoscopic total gastrectomy for gastric cancer is not a commonly
      performed procedure due to the technical difficulty. We devised a technique for
      intracorporeal esophagojejunostomy after laparoscopic total gastrectomy. In the
      reconstruction, nearly two thirds of the diameter of the esophagus was transected
      with an endoscopic linear stapler and the unstapled esophagus was transected with
      laparoscopic scissors. First suture was created at the end of the stapled line
      and second suture was created at the esophagostomy. During the reconstruction,
      assistants retracted the 2 sutures to prevent slippage of the esophageal stump
      into the thoracic cavity. Finally the remnant entry hole was closed with an
      endoscopic linear stapler. This reconstruction was successfully performed in all
      patients; none of the patients required conversion to open surgery. All
      operations were curative and there were no deaths. This method can be performed
      easily and safely, and may become a powerful alternative procedure for totally
      laparoscopic total gastrectomy. 

PMID- 24300935
TI  - Novel technique for full-thickness resection of gastric malignancy: feasibility
      of nonexposed endoscopic wall-inversion surgery (news) in porcine models.
AB  - Full-thickness resection for gastric malignancy carries a risk of peritoneal
      dissemination due to opening of the gastric lumen. We evaluated the feasibility
      and safety a novel method of full-thickness resection without transmural
      communication, called nonexposed endoscopic wall-inversion surgery in ex vivo and
      in vivo porcine models. Six explanted porcine stomachs and 6 live pigs were used
      for this study. After marking and submucosal injection around 3 cm simulated
      lesions, the seromuscular layer was laparoscopically cut and sutured with the
      lesion inverted to the inside. Consecutively, a mucosubmucosal incision was made
      endoscopically. Three pigs used for the survival study were monitored for 7 days.
      All 12 lesions were successfully resected en bloc without perforation. The 3 pigs
      survived for 1 week without adverse events, and necropsy revealed neither leakage
      nor abscess formation related to the operation. We demonstrated nonexposed
      endoscopic wall-inversion surgery to be technically feasible and safe in both ex
      vivo and in vivo porcine studies. 

PMID- 24300936
TI  - A novel totally internal laparoscopic liver retractor.
AB  - INTRODUCTION: Minimally invasive surgery is still in evolution. Throughout the
      past two decades numerous devices have been developed to enable safer and faster
      procedures, including anastomosis creating devices, energy sources, and superior
      imaging. However, retraction capabilities were put aside and currently, organ
      laparoscopic retraction is based on standard laparoscopic tools. In the era of
      minimizing the number of ports and shrinking their size, our aim was to develop
      internal retraction device that could be placed in the peritoneal cavity through
      a standard trocar, positioned for adequate retraction, and left in place for the
      entire procedure. These devices would obviate the need for inserting ports
      dedicated for retraction only and hence contribute to the reduction of the number
      of incisions. Herein, we present our initial experience with a novel internal
      liver retractor. MATERIALS AND METHODS: The Endolift retractor is a simple
      telescopic rod that has anchoring claws at each end. It can be inserted using 5
      mm standard trocar using a dedicated applier and anchored to the peritoneum
      beside the liver edges thereby lifting the undersurface of the liver and exposing
      the organs underneath. To achieve retraction of the left lateral segment, the
      Endolift retractor is anchored lateral to the right diaphragmatic crus on 1 side
      and lateral to the falciform ligament on the other. RESULTS: A total of 14
      operations were performed using the Endolift retractor for liver retraction
      including antireflux procedure, robotic-assisted Heller's myotomy, bariatric
      procedures, and bile duct exploration. The left lobe of the liver was adequately
      retracted and enabled access to the operating field. Repositioning was easily
      performed with progression of the surgery when necessary. CONCLUSIONS: Internal
      retraction devices such as the Endolift retractor for liver retraction are one
      step further in minimizing trauma to the abdominal wall during minimal invasive
      surgery. It obviates the need for extra incisions, frees up the surgeons' hands,
      and may enable performing complicated laparo-endoscopic single-site laparoscopy
      and natural orifice transluminal endoscopic surgery.

PMID- 24300937
TI  - Endoscopic closure of ERCP-related duodenal perforations by using endoclips: a
      case series.
AB  - Duodenal wall perforations are traditionally managed surgically. There are
      isolated case reports or small case series reporting successful endoscopic
      closure of duodenal perforations. Endoscopic closure techniques include the use
      of endoclips, fibrin glue, and endoloops. Herein we report the largest series
      containing 4 cases of successful endoscopic closure of iatrogenic duodenal
      perforations related to endoscopic retrograde cholangiopancreatography by using
      endoclips and briefly review the endoscopic methods used in the closure of
      perforations in the light of current literature. 

PMID- 24300938
TI  - The use of laser lithotripsy status post cholecystostomy tube placement without
      interval cholecystectomy for calculous cholecystitis in a patient unfit for
      general anesthesia.
AB  - Acute cholecystitis in patients unfit for general anesthesia often initially
      requires cholecystectomy tube placement without cholecystectomy. The best way to
      definitively manage those patients with irreversible medical conditions, leaving
      them unable to undergo cholecystectomy, has yet to be defined. Laser lithotripsy
      is currently used in the management of stones of the genitourinary system.
      Extracorporeal shock wave cholelithotripsy has been extensively evaluated in
      Munich, Germany and since then, has been abandoned as an alternative treatment of
      cholelithiasis. This report discusses a novel approach using established
      cholecystocutaneous fistula tracts and laser lithotripsy to definitively treat
      this group of patients. 

PMID- 24300939
TI  - Computerized tomography providing definitive diagnosis of colonic lipoma: a case
      series.
AB  - Lipomas are common benign mesenchymal tumors. They can develop in virtually all
      organs throughout the body. Colonic lipomas are uncommon, benign, submucosal
      adipose tumors that are usually asymptomatic. Large lipomas can cause symptoms
      such as constipation, abdominal pain, rectal bleeding, and intussusception. We
      report a case series of 2 colonic submucosal lipomas with varying clinical
      presentations, elaborating the importance of computerized tomography imaging in
      the diagnosis and preoperative planning. 

PMID- 24300940
TI  - Fistula fiberscope-assisted percutaneous glue sealing for enterocutaneous
      fistulas: a case report.
AB  - Endoscopic therapy is a valuable option for glue sealing in fistula patients with
      low-output volume to enable more complete filling of internal openings. However,
      no special endoscopes were designed and made for fistula tracts. This brief
      report concerns about the application of an autologous platelet-rich fibrin
      sealant through a refined fistula fiberscope. Symptoms achieved resolutions and
      the follow-up computed tomography scans revealed no intestinal fluid leakage. To
      our knowledge, this is the first report on this percutaneous endoscope-assisted
      glue procedure. 

PMID- 24300941
TI  - High-throughput flow cytometry cell-based assay to detect antibodies to N-methyl
      D-aspartate receptor or dopamine-2 receptor in human serum.
AB  - Over the recent years, antibodies against surface and conformational proteins
      involved in neurotransmission have been detected in autoimmune CNS diseases in
      children and adults. These antibodies have been used to guide diagnosis and
      treatment. Cell-based assays have improved the detection of antibodies in patient
      serum. They are based on the surface expression of brain antigens on eukaryotic
      cells, which are then incubated with diluted patient sera followed by
      fluorochrome-conjugated secondary antibodies. After washing, secondary antibody
      binding is then analyzed by flow cytometry. Our group has developed a high
      throughput flow cytometry live cell-based assay to reliably detect antibodies
      against specific neurotransmitter receptors. This flow cytometry method is
      straight forward, quantitative, efficient, and the use of a high-throughput
      sampler system allows for large patient cohorts to be easily assayed in a short
      space of time. Additionally, this cell-based assay can be easily adapted to
      detect antibodies to many different antigenic targets, both from the central
      nervous system and periphery. Discovering additional novel antibody biomarkers
      will enable prompt and accurate diagnosis and improve treatment of immune
      mediated disorders. 

PMID- 24300942
TI  - A Protein Phosphatase 1 involved in correct nucleus positioning in trypanosomes.
AB  - Reversible protein phosphorylation is a key regulator in intracellular functions.
      In the African trypanosome, Trypanosoma brucei, the serine-threonine phosphatase
      PP1-3, is localised in the cytoplasm. RNAi mediated knockdown of PP1-3 leads to a
      coordinated rearrangement of cellular organelles and compartments in the
      procyclic trypanosome. These parasites display their nucleus at the very
      posterior end of the cell. The kinetoplast is very close to the nucleus, and
      often located in a more anterior position. The lysosomal compartment, which in a
      normal procyclic cell is situated between nucleus and kinetoplast, is now
      positioned towards the anterior end of the cell. The Flagellum Attachment Zone,
      essential for cytokinesis, is still constructed, allowing initiation of the
      cleavage furrow and cell division. These adaptations allow dividing cells to
      distribute their organelles among the daughter cells and to proliferate normally.
      PP1-3 is therefore essential in conserving the intracellular organisation of the
      procyclic trypanosome cell. 

PMID- 24300944
TI  - Patients must have single point of contact for care needs, says think tank.

PMID- 24300943
TI  - Anticancer metal complexes: synthesis and cytotoxicity evaluation by the MTT
      assay.
AB  - Titanium (IV) and vanadium (V) complexes are highly potent anticancer agents. A
      challenge in their synthesis refers to their hydrolytic instability; therefore
      their preparation should be conducted under an inert atmosphere. Evaluation of
      the anticancer activity of these complexes can be achieved by the MTT assay. The
      MTT assay is a colorimetric viability assay based on enzymatic reduction of the
      MTT molecule to formazan when it is exposed to viable cells. The outcome of the
      reduction is a color change of the MTT molecule. Absorbance measurements relative
      to a control determine the percentage of remaining viable cancer cells following
      their treatment with varying concentrations of a tested compound, which is
      translated to the compound anticancer activity and its IC50 values. The MTT assay
      is widely common in cytotoxicity studies due to its accuracy, rapidity, and
      relative simplicity. Herein we present a detailed protocol for the synthesis of
      air sensitive metal based drugs and cell viability measurements, including
      preparation of the cell plates, incubation of the compounds with the cells,
      viability measurements using the MTT assay, and determination of IC50 values. 

PMID- 24300945
TI  - The effectiveness of the promotion of newborn hearing screening in Taiwan.
AB  - OBJECTIVE: Hearing is a critical ability for the development of a child's speech
      and language. Many studies in different countries have shown the universal
      newborn hearing screening and early intervention has greatly reduced the negative
      impact caused by congenital hearing loss. The first universal newborn hearing
      screening program in Taiwan took place in MacKay Memorial Hospital in 1998 and
      was subsequently endorsed by the government. The incidence of bilateral
      congenital hearing impairment in Taiwan is approximately 2.6 per 1000 live birth.
      The aim of this paper is to analyze the age of diagnosis, hearing aid fitting,
      and intervention of congenitally hearing impaired children with and without
      hearing screening after public awareness and government endorsement of newborn
      hearing screening. MATERIALS AND METHODS: There were 263 hearing impaired
      children participated in this study, receiving their auditory habilitation
      therapy at Children's Hearing Foundation from 2006 to 2010. 114 of those children
      went through newborn hearing screening and 149 without it. The age of diagnosis,
      hearing aid fitting, and auditory intervention were compared between these two
      groups. The age of diagnosis and intervention of congenitally hearing impaired
      children among different years were analyzed too. RESULTS: The average age of
      diagnosis was 8.7 months, the age of hearing aid fitting was 12.4 months and age
      of auditory intervention was 18.8 months for the group of hearing impaired
      children with newborn hearing screening. For hearing impaired children without
      newborn screening, their average age of diagnosis was 27.5 months; age of hearing
      aid fitting was 31.3 months and age of auditory intervention was 40.5 months.
      There were significant differences in the age of diagnosis, hearing aid fitting
      and auditory intervention between congenitally hearing impaired children with and
      without hearing screening. CONCLUSIONS: This research indicates that newborn
      hearing screening facilitates early identification, diagnosis and intervention of
      congenitally hearing impaired children in Taiwan. The age of identification,
      diagnosis and intervention of congenital hearing impaired children has also been
      reduced gradually over the years after government endorsement of newborn hearing
      screening in Taiwan.

PMID- 24300946
TI  - Evaluation of maxillary arch dimensions and palatal morphology in mouth-breathing
      children by using digital dental casts.
AB  - OBJECTIVE: The aim of the present study was to analyze the variations of
      maxillary arch size and of palatal morphology in subjects with prolonged mouth
      breathing due to allergic rhinitis when compared with a control group with normal
      breathing pattern by using a three-dimensional analysis on digital casts.
      METHODS: 26 Caucasian children (19 females and 7 males) with a mean age of 8.5
      years (SD 1.6 years) were selected according to the following criteria: mouth
      breathing pattern due to allergic rhinitis, early mixed dentition, skeletal Class
      I relationship and prepubertal stage of cervical vertebral maturation. The study
      group was compared with a control group of 17 nasal breathing subjects (9
      females; 8 males, mean age 8.5 years SD 1.7 years). For each subject an initial
      dental cast was taken and the upper arch was scanned by using a tridimensional
      scanner. On each digital model linear measurements were performed to analyze
      maxillary arch dimensions and palatal morphology. Significant between-group
      differences were tested with the Student t-test (p<0.05). RESULTS: the transverse
      dimension of the upper arch was significantly smaller in subjects of the study
      group thus confirming the influence of oral breathing on skeletal development
      with a significant constriction of the whole palate. The study group showed a
      higher and sharper palatal vault at the level of second deciduous molars and of
      first permanent molars. CONCLUSIONS: Children with mouth-breathing pattern showed
      a significant constriction of the maxillary arch and an increased palatal height
      when compared with subjects with normal breathing pattern.

PMID- 24300947
TI  - Autism and peripheral hearing loss: a systematic review.
AB  - OBJECTIVE: To systematically review the literature describing the relationship
      between autism spectrum disorder (ASD) and peripheral hearing loss including
      literature recommendations for audiological assessment and auditory habilitation
      in cases where peripheral hearing loss and ASD coexist. DATA SOURCES: Published
      studies indexed in MEDLINE (1948-2011). REVIEW METHODS: The search strategy
      identified 595 potential studies. After a review of the titles, 115 abstracts
      were reviewed and 39 articles were retrieved and assessed independently by at
      least two authors for possible inclusion. 22 articles pertained to children with
      ASD and peripheral hearing loss, hearing assessment in children with ASD,
      audiological habilitation for children with ASD or hyper-responsiveness in
      children with ASD. 17 further studies were garnered from the reference section of
      the 22 papers. RESULTS: Controversy exists in the literature regarding prevalence
      of hearing impairment among individuals with ASD. In cases where ASD and hearing
      impairment co-exist, diagnosis of one condition often leads to a delay in
      diagnosing the other. Audiological assessment can be difficult in children with
      ASD and test-retest reliability of behavioural thresholds can be poor. In cases
      where hearing impairment exists and hearing aids or cochlear implantation are
      recommended, devices are often fit with special considerations for the child with
      ASD. Hyper-responsiveness to auditory stimuli may be displayed by individuals
      with ASD. Evidence or the suspicion of hyper-responsiveness may be taken into
      consideration when fitting amplification and planning behavioural intervention.
      CONCLUSIONS: Prevalence rates of hearing impairment among individuals with ASD
      continue to be debated. At present there is no conclusive evidence that children
      with ASD are at increased risk of peripheral hearing loss. A complete
      audiological assessment is recommended in all cases where ASD is suspected so as
      not to delay the diagnosis of hearing impairment in the event that hearing loss
      and ASD co-exist. Objective assessment measures should be used to confirm
      behavioural testing in order to ensure reliability of audiological test results.
      Fitting of hearing aids or cochlear implantation are not contraindicated when
      hearing loss is present in children with ASD; however, success with these devices
      can be variable.

PMID- 24300949
TI  - Long-lasting effects of a new memory self-efficacy training for stroke patients:
      a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: This study aims to determine the long-term effects of a
      new Memory Self-efficacy (MSE) training program for stroke patients on MSE,
      depression, and quality of life. METHODS: In a randomized controlled trial,
      patients were allocated to a MSE training or a peer support group. Outcome
      measures were MSE, depression, and quality of life, measured with the Metamemory
      In-Adulthood questionnaire, Center for Epidemiological Studies-Depression Scale
      (CES-D), and the Who-Qol Bref questionnaire, respectively. We used linear mixed
      models to compare the outcomes of both groups immediately after training, after 6
      months, and after 12 months, adjusted for baseline. RESULTS: In total, 153 former
      inpatients from 2 rehabilitation centers were randomized-77 to the experimental
      and 76 to the control group. MSE increased significantly more in the experimental
      group and remained significantly higher than in the control group after 6 and 12
      months (B = 0.42; P = .010). Psychological quality of life also increased more in
      the experimental group but not significantly (B = 0.09; P = .077). However, in
      the younger subgroup of patients (<65 years old), psychological quality of life
      significantly improved in the experimental group compared to the control group
      and remained significantly higher over time (B = 0.14; P = .030). Other outcome
      measures were not significantly different between both groups. CONCLUSIONS: An
      MSE training program improved MSE and psychological quality of life in stroke
      patients aged <65 years. These effects persisted during 12 months of follow-up.

PMID- 24300948
TI  - Generation of osteochondral tissue constructs with chondrogenically and
      osteogenically predifferentiated mesenchymal stem cells encapsulated in bilayered
      hydrogels.
AB  - This study investigated the ability of chondrogenic and osteogenic
      predifferentiation of mesenchymal stem cells (MSCs) to play a role in the
      development of osteochondral tissue constructs using injectable bilayered
      oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites. We hypothesized
      that the combinatorial approach of encapsulating cell populations of both
      chondrogenic and osteogenic lineages in a spatially controlled manner within
      bilayered constructs would enable these cells to maintain their respective
      phenotypes via the exchange of biochemical factors even without the influence of
      external growth factors. During monolayer expansion prior to hydrogel
      encapsulation, it was found that 7 (CG7) and 14 (CG14) days of MSC exposure to
      TGF-beta3 allowed for the generation of distinct cell populations with
      corresponding chondrogenic maturities as indicated by increasing aggrecan and
      type II collagen/type I collagen expression. Chondrogenic and osteogenic cells
      were then encapsulated within their respective (chondral/subchondral) layers in
      bilayered hydrogel composites to include four experimental groups. Encapsulated
      CG7 cells within the chondral layer exhibited enhanced chondrogenic phenotype
      when compared to other cell populations based on stronger type II collagen and
      aggrecan gene expression and higher glycosaminoglycan-to-hydroxyproline ratios.
      Osteogenic cells that were co-cultured with chondrogenic cells (in the chondral
      layer) showed higher cellularity over time, suggesting that chondrogenic cells
      stimulated the proliferation of osteogenic cells. Groups with osteogenic cells
      displayed mineralization in the subchondral layer, confirming the effect of
      osteogenic predifferentiation. In summary, it was found that MSCs that underwent
      7 days, but not 14 days, of chondrogenic predifferentiation most closely
      resembled the phenotype of native hyaline cartilage when combined with osteogenic
      cells in a bilayered OPF hydrogel composite, indicating that the duration of
      chondrogenic preconditioning is an important factor to control. Furthermore, the
      respective chondrogenic and osteogenic phenotypes were maintained for 28 days in
      vitro without the need for external growth factors, demonstrating the exciting
      potential of this novel strategy for the generation of osteochondral tissue
      constructs for cartilage engineering applications.

PMID- 24300950
TI  - Circulating fibrocytes stabilize blood vessels during angiogenesis in a paracrine
      manner.
AB  - Accumulating evidence supports that circulating fibrocytes play important roles
      in angiogenesis. However, the specific role of fibrocytes in angiogenesis and the
      underlying mechanisms remain unclear. In this study, we found that fibrocytes
      stabilized newly formed blood vessels in a mouse wound-healing model by
      inhibiting angiogenesis during the proliferative phase and inhibiting blood
      vessel regression during the remodeling phase. Fibrocytes also inhibited
      angiogenesis in a Matrigel mouse model. In vitro study showed that fibrocytes
      inhibited both the apoptosis and proliferation of vascular endothelial cells
      (VECs) in a permeable support (Transwell) co-culture system. In a three
      dimensional collagen gel, fibrocytes stabilized the VEC tubes by decreasing VEC
      tube density on stimulation with growth factors and preventing VEC tube
      regression on withdrawal of growth factors. Further mechanistic investigation
      revealed that fibrocytes expressed many prosurvival factors that are responsible
      for the prosurvival effect of fibrocytes on VECs and blood vessels. Fibrocytes
      also expressed angiogenesis inhibitors, including thrombospondin-1 (THBS1). THBS1
      knockdown partially blocked the fibrocyte-induced inhibition of VEC proliferation
      in the Transwell co-culture system and recovered the fibrocyte-induced decrease
      of VEC tube density in collagen gel. Purified fibrocytes transfected with THBS1
      siRNA partially recovered the fibrocyte-induced inhibition of angiogenesis in
      both the wound-healing and Matrigel models. In conclusion, our findings reveal
      that fibrocytes stabilize blood vessels via prosurvival factors and anti
      angiogenic factors, including THBS1. 

PMID- 24300951
TI  - Ex vivo pathogenicity of anti-laminin gamma1 autoantibodies.
AB  - Autoimmunity against laminins has been described in several autoimmune diseases
      (including mucous membrane pemphigoid, anti-laminin gamma1 pemphigoid, and
      connective tissue diseases), in pregnancy loss, and in infections such as Chagas
      disease. Except for anti-laminin-332 mucous membrane pemphigoid, adequate
      evidence has been lacking for the tissue injury potential of laminin-specific
      antibodies and the pathogenic epitopes. We evaluated the pathogenic potential of
      antibodies targeting laminin gamma1, a major constituent of basement membranes
      and the main antigen in anti-laminin gamma1 pemphigoid. Rabbit antibodies were
      generated against fragments of the N-terminus and C-terminus of murine laminin
      gamma1, and their ability to disrupt ligand interactions and/or to activate
      complement and granulocytes was assessed using previously established ex vivo
      assays. Our findings document a pathogenic potential of antibodies targeting the
      laminin gamma1 N-terminus. These antibodies interfere with the binding of nidogen
      to laminin and can activate granulocytes and the complement cascade. We detected
      antibodies with different degrees of reactivity with laminin gamma1 N-terminus in
      patients with anti-laminin gamma1 pemphigoid, cutaneous lupus erythematosus, and
      scleroderma. Our results provide mechanistic insights into the tissue damage
      associated with laminin autoimmunity and could facilitate development of
      appropriate diagnostic tools and therapeutic strategies. 

PMID- 24300952
TI  - FLOWERING LOCUS T genes control onion bulb formation and flowering.
AB  - Onion (Allium cepa L.) is a biennial crop that in temperate regions is planted in
      the spring and, after a juvenile stage, forms a bulb in response to the
      lengthening photoperiod of late spring/summer. The bulb then overwinters and in
      the next season it flowers and sets seed. FLOWERING LOCUS T (FT) encodes a mobile
      signaling protein involved in regulating flowering, as well as other aspects of
      plant development. Here we show that in onions, different FT genes regulate
      flowering and bulb formation. Flowering is promoted by vernalization and
      correlates with the upregulation of AcFT2, whereas bulb formation is regulated by
      two antagonistic FT-like genes. AcFT1 promotes bulb formation, while AcFT4
      prevents AcFT1 upregulation and inhibits bulbing in transgenic onions. Long-day
      photoperiods lead to the downregulation of AcFT4 and the upregulation of AcFT1,
      and this promotes bulbing. The observation that FT proteins can repress and
      promote different developmental transitions highlights the evolutionary
      versatility of FT. 

PMID- 24300953
TI  - Advances in neonatal care.

PMID- 24300956
TI  - Pain assessment and measurement in neonates: an updated review.
AB  - Pain assessment and measurement are the cornerstones of pain management. Pain
      assessment connotes a comprehensive multidimensional description. Conversely,
      pain measurement provides a numeric quantitative description of each factor
      illustrating pain qualities. Pain scales provide a composite score used to guide
      practice and research. The type of infant pain instrument chosen is a significant
      factor in guiding pain management practice. The purpose of this review was to
      summarize current infant pain measures by introducing a conceptual framework for
      pain measurement. Although more than 40 infant pain instruments exist, many were
      devised solely for research purposes; several of the newly developed instruments
      largely overlap with existing instruments. Integration of pain management into
      daily practice remains problematic. Understanding how each instrument measures
      infant pain allows clinicians to make better decisions about what instrument to
      use with which infant and in what circumstances. In addition, novel new
      measurement techniques need further testing. 

PMID- 24300957
TI  - Heart rate characteristics in the NICU: what nurses need to know.
AB  - Late-onset sepsis continues to be a significant cause of morbidity and mortality
      in very low-birth-weight infants. Earlier detection of infection with heart rate
      variability monitoring through the use of the HeRO monitor has been shown to
      reduce mortality rate by 22%. This article reviews how HeRO is used to assist in
      earlier diagnosis and treatment of infection. 

PMID- 24300958
TI  - Vitamin K deficiency bleeding: a case study.
AB  - Vitamin K deficiency bleeding (VKDB), formerly known as hemorrhagic disease of
      the newborn (HDN), is a bleeding disorder in neonates that is caused by
      inadequate serum levels of vitamin K. Vitamin K is a nutrient essential for
      adequate function of the coagulation cascade. Certain internal and external
      factors place newborn infants at higher risk for VKDB. Therefore, vitamin K
      prophylaxis has become the standard of care for newborns. Although the American
      Academy of Pediatrics recommends the administration of vitamin K to newborns,
      some parents are choosing to withhold vitamin K administration at birth. This
      case study describes an infant who developed VKDB in the absence of vitamin K
      prophylaxis. Although parents ultimately have the right to choose whether or not
      to administer vitamin K, as healthcare professionals, it is important to provide
      education regarding the potential complications of withholding vitamin K and the
      signs of VKDB if vitamin K prophylaxis at birth is withheld. 

PMID- 24300959
TI  - Neonatal palliative care: developing consensus among neonatologists using the
      Delphi technique in Portugal.
AB  - Pediatric palliative care in Portugal is improving, but there is still additional
      work to do concerning programs or guidelines for this subject. In Portugal,
      physicians are the stakeholders in the decision-making process with reference to
      the transition to palliative care in the neonatal intensive care unit, and it was
      considered very important to raise their awareness and motivation about neonatal
      palliative care. Our research was based on Catlin and Carter's protocol from 2002
      and the main goal was to assess neonatologists' willingness to build a palliative
      care and end-of-life protocol that could be acceptable nationwide. The survey
      used the Delphi technique and was developed in 3 rounds. The expert panel was
      composed of 57 participants who represented 41% of the Portuguese neonatologists.
      The study was conducted via the Internet, based in a researcher-created private
      Web site, and e-mail was used for data collection and feedback. Neonatologists
      agreed on 7 areas: (1) planning (medical education, resources, and local), (2)
      prenatal palliative care, (3) neonatal palliative care criteria, (4) the parents
      (presenting neonatal palliative care to parents, including then in the daily care
      of newborns and in family-centered care), (5) physicians' needs, (6) pain and
      symptom management, and (7) end-of-life care (withholding/withdrawing ventilation
      and hydration/nutrition). 

PMID- 24300960
TI  - While waiting: early recognition and initial management of neonatal hypoxic
      ischemic encephalopathy.
AB  - Hypoxic-ischemic encephalopathy (HIE) occurring during the perinatal period is
      one of the primary causes of severe, long-term neurological deficits in children.
      Initial systemic supportive therapy remains a critical aspect of HIE management.
      In addition to support therapy, the widespread use of hypothermia has
      demonstrated a reduction in death and neurodevelopmental disability in infants
      with moderate to severe HIE. Neonates with HIE born outside of tertiary care
      centers must be rapidly identified as hypothermia candidates and have emergent
      transport arranged. While waiting for the transport team to arrive, these
      neonates often require intensive stabilization, including meticulous temperature
      management. This article examines the need for HIE outreach teaching programs,
      assists in the identification of a neonate for hypothermia therapy, and supplies
      evidence-based recommendations for the initial stabilization and care of neonates
      delivered at nontertiary care facilities. The guidelines and materials supplied
      represent the outreach model used by our regional hypothermia center and
      disseminated to the surrounding referral hospitals. 

PMID- 24300962
TI  - Options for securing umbilical catheters.

PMID- 24300963
TI  - Validation of the Finnegan neonatal abstinence syndrome tool-short form.
AB  - PURPOSE: The purpose of this study was to reduce the number of items in the
      Modified Finnegan Neonatal Abstinence Syndrome Tool (M-FNAST) to the minimum
      possible while retaining or improving its validity in a short version. SUBJECTS:
      All infants with a diagnosis of neonatal abstinence syndrome (171) who were
      admitted to a large neonatal intensive care unit in southwest Florida between
      September 2010 and October 2012 comprised the sample. DESIGN: This was a
      psychometric evaluation of 33 856 M-FNAST assessments that were downloaded from
      the electronic medical record. METHODS: Principal axis factoring extraction with
      varimax rotation was performed on the M-FNAST data. Principal components
      extraction was used before principal factors extraction to estimate the number of
      factors with the scree test and factorability of the correlation matrices with
      Bartlett's chi-square test, and Kaiser-Meyer-Olkin Measure of Sampling Adequacy.
      RESULTS: The M-FNAST scores ranged from 0 to 29, with a mean of 3.5 (SD = 2.5).
      Less than 1% (21) of infants had scores of 17 or more. Nearly all (97.7%) scores
      fell between 0 and 9. Most subjects were full-term gestation, but 11 were preterm
      between 28 and 37 weeks' gestational age. The 2-factor solution explained 23.74%
      of the total variance and consists of 2 factors, mild/early and moderate/advanced
      signs. The 2-factor solution was significantly correlated with the total score on
      the MFNAST (r = 0.917; P < .001). Among infants who scored 8 or greater, the
      total score on the 2-factor solution short form FNAST was significantly
      correlated with the total score on the M-FNAST (r = 0.629; P < .001).

PMID- 24300964
TI  - The emotional experiences and supports for parents with babies in a neonatal
      nursery.
AB  - PURPOSE: The experience of the neonatal intensive care unit (NICU) for parents
      can be anxiety-provoking, fearful, and distressing. To help parents cope with
      these overwhelming feelings, a number of interventions, including parent support
      groups, are typically offered. It is hoped that the provision of these groups and
      other forms of emotional support lessen the distressing experience for parents
      and lessen the anxiety of hospital discharge. This study focuses on the emotional
      reactions during the transition to home from the NICU for parents who
      participated in one such support group. METHODS: Parents were interviewed 4 to 6
      months after discharge of their baby from hospital. RESULTS: Themes from these
      interviews included anxiety and concern about the baby's readiness for discharge,
      concerns about the risks of further illness and rehospitalization, and whether
      the parent felt prepared sufficiently to care for his or her baby at home.
      Recalling their time in the nursery was distressing for parents, but despite
      this, they identified that positive staff interactions helped them through the
      hardest times in the NICU. CONCLUSIONS: The support group was reported to be
      effective and helpful for parents. Parents often maintained social contact with
      other parents and recalled advice and supportive information from the group as
      needed. Participants recommended that the support group continue to assist other
      parents.

PMID- 24300965
TI  - Enteral feeding misconnections in the NICU: a continuing patient safety threat.
AB  - Although the first case of tubing misconnection was reported in 1972, this
      patient safety issue received little national attention until The Joint
      Commission issued a Sentinel Event Alert in the spring of 2006. This was followed
      by a "Money and Policy" article in the New York Times in the summer of 2010 that
      initiated a public awareness outcry against the healthcare system's delayed
      responsiveness in creating fail safe solutions. Since that time, many
      manufacturers have devised oral syringes, feeding tubes, and feeding "systems"
      for patients in the neonatal intensive care unit, but these devices' ability to
      minimize risk is not well delineated. This article reviews the history of tubing
      misconnections and provides an in-depth look at current recommendations for
      manufacturing and device design, human factors contributing to misconnections,
      and specific strategies for minimizing patient safety risk. 

PMID- 24300966
TI  - Optimizing protein intake in premature infants: a neonatal quality improvement
      project.
AB  - This article examines a quality-improvement project to reduce clinical practice
      variation and measure growth outcomes by standardizing the process for the
      provision of protein intake for premature infants weighing 1250 g or less.
      Eighteen infants with a birth weight of 1250 g or less and gestational age of 32
      weeks or less born between June and October 2010 were compared with 15 historical
      controls of the same birth weight and gestation born between January and May 2010
      using a prospective cohort design. The prospective group followed a newly
      implemented standardized protein nutritional guideline. Independent t-tests and
      repeated measures of analyses of variance (between- and within-subjects) were
      performed on the difference between the intended and actual protein intakes
      between the 2 groups. A multivariate analysis of variance computed the difference
      between the birth and discharge gains. The prospective group showed statistically
      significant differences between the amount of intended and actual protein intakes
      (P = .023) when compared with historical controls. Growth outcomes were not
      significantly different (P = .67) between the 2 groups. Length of stay was not
      statistically significantly shorter (P = .06) in the prospective group. Reduction
      in clinical practice variation was associated with the implementation of a
      protein nutritional guideline. There was no statistical support for an
      improvement in the growth outcomes or reduction in length of stay. 

PMID- 24300967
TI  - A simple cassette as point-of-care diagnostic device for naked-eye colorimetric
      bacteria detection.
AB  - Effective pathogen detection is necessary for treatment of infectious diseases.
      Point of care (POC) devices have tremendously improved the global human heath.
      However, design criteria for sample processing POC devices for pathogen detection
      in limited infrastructure are challenging and can make a significant contribution
      to global health by providing rapid and sensitive detection of bacteria in food,
      water, and patient samples. In this paper, we demonstrate a novel portable POC
      diagnostic device that is simple to assemble for genetic detection of bacterial
      pathogens by isothermal DNA amplification. The device is fabricated with very low
      production cost, using simple methods and easy-to-access materials on a flexible
      ribbon polyethylene substrate. We showed that the device is capable of detection
      of 30 CFU mL(-1) of E. coli and 200 CFU mL(-1) of S. aureus in less than 1 hour.
      Through numerical simulations, we estimated that the device can be extended to
      high-throughput detection simultaneously performing a minimum of 36 analyses.
      This robust and sensitive detection device can be assembled and operated by non
      specialist personnel, particularly for multiple bacterial pathogen detections in
      low-resource settings. 

PMID- 24300968
TI  - Determination of the shielding factors for gamma-ray spectrometers.
AB  - A method for determining the shielding factors for gamma-ray spectrometers is
      described. The shielding factors are expressed by decomposing the peaked
      background of the spectrometer into contributions of the detector, spectrometer
      shield and ambient radiation to the spectrometer background. The dimensions of
      the sample and its mass-attenuation coefficient are taken into account using a
      simple model. For six spectrometers, with contributions to the background
      quantified, the shielding factors were determined for the background based on the
      thorium decay series and the radon daughters. For a water sample with a diameter
      of 9 cm and a thickness of 4 cm and the nuclides of the thorium decay series that
      are in the spectrometer shields, the values of the shielding factors lie in the
      interval 0.95-1.00. For a spectrometer exhibiting the diffusion of radon into the
      shielding material, the values of the shielding factors for the same sample for
      gamma-rays from the radon daughters lie in the interval 0.88-1.00.

PMID- 24300969
TI  - Optimization of a measurement facility for radioactive waste free release by
      Monte Carlo simulation.
AB  - A novel free release measurement facility (FRMF) was developed within the joint
      research project "Metrology for Radioactive Waste Management" of the European
      Metrology Research Programme. Before and during FRMF design and construction,
      Monte Carlo calculations with MCNPX and PENELOPE codes were used to optimize the
      thickness of the shielding, the dimensions of the container, and the shape of
      detector collimators. Validation of the numerical models of the FRMF detectors
      and the results of the optimization are discussed in the paper. 

PMID- 24300970
TI  - Comment on 'Anti-tumour activity of abiraterone and diethylstilboestrol when
      administered sequentially to men with castration-resistant prostate cancer'.

PMID- 24300971
TI  - Extramural venous invasion is a potential imaging predictive biomarker of
      neoadjuvant treatment in rectal cancer.
AB  - BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in
      rectal cancer and identified on magnetic resonance imaging (MRI) (mrEMVI). The
      clinical relevance of improvement in mrEMVI following neoadjuvant therapy is
      unknown. This study aimed to demonstrate that regression of mrEMVI following
      neoadjuvant chemoradiotherapy (CRT) results in improved outcomes and mrEMVI can
      be used as an imaging biomarker. METHODS: Retrospective analysis of prospectively
      collected data was conducted examining the staging and post-treatment MRIs of
      patients who had presented with EMVI-positive rectal cancer. All patients had
      undergone neoadjuvant CRT and curative surgery. Changes in mrEMVI were graded
      with a new MRI-based TRG scale-mr-vTRG; and related to disease-free survival
      (DFS). The study fulfilled Reporting Recommendations for Tumour Marker Prognostic
      Studies criteria for biomarkers. RESULTS: Sixty-two patients were included.
      Thirty-five patients showed more than 50% fibrosis of mrEMVI (mr-vTRG 1-3); 3
      year DFS 87.8% and 9% recurrence. Twenty-seven patients showed less than 50%
      fibrosis (mr-vTRG 4-5); 3-year DFS 45.8% with 44% recurrence - P<0.0001. On
      multivariate Cox-regression, only mr-vTRG 4-5 increased risk of disease
      recurrence - HR=5.748. CONCLUSION: Patients in whom there has been a significant
      response of EMVI to CRT show improved DFS. Those patients with poor response
      should be considered for intensive treatment. As an imaging biomarker in rectal
      cancer, mrEMVI can be used.

PMID- 24300972
TI  - CD44s signals the acquisition of the mesenchymal phenotype required for anchorage
      independent cell survival in hepatocellular carcinoma.
AB  - BACKGROUND: Circulating tumour cells (CTCs) have an important role in metastatic
      processes, but details of their basic characteristics remain elusive. We
      hypothesised that CD44-expressing CTCs show a mesenchymal phenotype and high
      potential for survival in hepatocellular carcinoma (HCC). METHODS: Circulating
      CD44(+)CD90(+) cells, previously shown to be tumour-initiating cells, were sorted
      from human blood and their genetic characteristics were compared with those of
      tumour cells from primary tissues. The mechanism underlying the high survival
      potential of CD44-expressing cells in the circulatory system was investigated in
      vitro. RESULTS: CD44(+)CD90(+) cells in the blood acquired epithelial-mesenchymal
      transition, and CD44 expression remarkably increased from the tissue to the
      blood. In Li7 and HLE cells, the CD44(high) population showed higher anoikis
      resistance and sphere-forming ability than did the CD44(low) population. This
      difference was found to be attributed to the upregulation of Twist1 and Akt
      signal in the CD44(high) population. Twist1 knockdown showed remarkable reduction
      in anoikis resistance, sphere formation, and Akt signal in HLE cells. In
      addition, mesenchymal markers and CD44s expression were downregulated in the
      Twist1 knockdown. CONCLUSIONS: CD44s symbolises the acquisition of a mesenchymal
      phenotype regulating anchorage-independent capacity. CD44s-expressing tumour
      cells in peripheral blood are clinically important therapeutic targets in HCC.

PMID- 24300973
TI  - Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy
      effectiveness and prognosis of gastric cancer patients following perioperative
      chemotherapy and radical gastrectomy.
AB  - BACKGROUND: DAP3 is a member of the death-associated protein (DAP) family and is
      characterised by proapoptotic function. It is involved in both exogenous and
      endogenous apoptotic pathways. In our previous studies, apoptotic level was found
      to be correlated with the effectiveness of preoperative chemotherapy. The
      effectiveness of preoperative chemotherapy was also associated with the overall
      effectiveness of the combined therapy and prognosis. The present study aimed to
      investigate the role of DAP3 in the evaluation of preoperative chemotherapy
      effectiveness and its ability to predict prognosis in gastric cancer. METHODS:
      Quantitative PCR and immunohistochemistry staining were performed in 87 patients
      who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer
      cell lines to investigate its impact on cell growth, migration, adhesion and
      invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis
      and caspase-3. RESULTS: Higher DAP3 expression in gastric tumours was correlated
      with better prognosis. Knockdown of DAP3 expression promoted cell migration and
      enhanced resistance to chemotherapy by inhibiting apoptosis. CONCLUSION: DAP3 is
      a potential molecular marker for response to preoperative chemotherapy and for
      predicting prognosis in gastric cancer patients treated with neoadjuvant
      chemotherapy and gastrectomy.

PMID- 24300975
TI  - Reply: 'Comment on Anti-tumour activity of abiraterone and diethylstilboestrol
      when administered sequentially to men with castration-resistant prostate cancer'.

PMID- 24300976
TI  - Breast cancer survival and prognosis by screening history.
AB  - BACKGROUND: Cancers not detected by breast screening are commonly assumed to have
      poorer prognosis. METHODS: We examined the survival experience of all women aged
      50-74 years diagnosed with a first breast cancer between 1998 and 2006 in British
      Columbia, Canada and determined their screening experience. Disease-specific
      survival rates were calculated and, for cases diagnosed in 2002, prognostic
      factors (size, nodal involvement, grade ER status and stage) were examined by
      time since screening. RESULTS: Breast cancers diagnosed at screening had the best
      survival (P<0.001). Cancers detected within 12 months of a negative screen had
      similar survival rates (P=0.98) to those diagnosed within 12-23 and 24-47 months,
      with other non-screen-detected cancers having poorer survival (P<0.001). The
      prognostic profile of cancers diagnosed in 2002 followed a similar pattern.
      INTERPRETATION: There was no evidence that cancers diagnosed within 12 months had
      poorer prognosis than those diagnosed up to 48 months following screening.

PMID- 24300974
TI  - Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non
      small-cell lung cancer through suppressing NF-kappaB and MAPK/HO-1 signalling.
AB  - BACKGROUND: Gambogic acid (GA) has been reported to have potent anticancer
      activity and is authorised to be tested in phase II clinical trials for treatment
      of non-small-cell lung cancer (NSCLC). The present study aims to investigate
      whether GA would be synergistic with cisplatin (CDDP) against the NSCLC. METHODS:
      1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)
      isobologram, western blot, quantitative PCR, flow cytometry, electrophoretic
      mobility shift assay, xenograft tumour models and terminal deoxynucleotide
      transferase-mediated dUTP nick-end labelling analysis were used in this study.
      RESULTS: The cell viability results showed that sequential CDDP-GA treatment
      resulted in a strong synergistic action in A549, NCI-H460, and NCI-H1299 cell
      lines, whereas the reverse sequence and simultaneous treatments led to a slight
      synergistic or additive action. Increased sub-G1 phase cells and enhanced PARP
      cleavage demonstrated that the sequence of CDDP-GA treatment markedly increased
      apoptosis in comparison with other treatments. Furthermore, the sequential
      combination could enhance the activation of caspase-3, -8, and 9, increase the
      expression of Fas and Bax, and decrease the expression of Bcl-2, survivin and X
      inhibitor of apoptosis protein (X-IAP) in A549 and NCI-H460 cell lines. In
      addition, increased apoptosis was correlated with enhanced reactive oxygen
      species generation. Importantly, it was found that, followed by CDDP treatment,
      GA could inhibit NF-kappaB and mitogen-activated protein kinase (MAPK)/heme
      oxygenase-1 (HO-1) signalling pathways, which have been validated to reduce ROS
      release and confer CDDP resistance. The roles of NF-kappaB and MAPK pathways were
      further confirmed by using specific inhibitors, which significantly increased ROS
      release and apoptosis induced by the sequential combination of CDDP and GA.
      Moreover, our results indicated that the combination of CDDP and GA exerted
      increased antitumour effects on A549 xenograft models through inhibiting NF
      kappaB, HO-1, and subsequently inducing apoptosis. CONCLUSION: Gambogic acid
      sensitises lung cancer cells to CDDP in vitro and in vivo in NSCLC through
      inactivation of NF-kappaB and MAPK/HO-1 signalling pathways, providing a
      rationale for the combined use of CDDP and GA in lung cancer chemotherapy.

PMID- 24300977
TI  - Progesterone receptor expression is an independent prognostic variable in early
      breast cancer: a population-based study.
AB  - BACKGROUND: Progesterone receptor (PR) expression assessment in early invasive
      breast cancer remains controversial. This study sought to re-evaluate PR
      expression as a potential therapeutic guide in early breast cancer; particularly
      in oestrogen receptor (ER)-positive, lymph node (LN)-negative disease. METHODS: A
      population cohort of 1074 patients presenting to a single Cancer Centre over 4
      years (2000-2004) underwent surgery for primary invasive breast cancer with
      curative intent. Prospective data collection included patient demographics,
      pathology, ER and PR expression, HER2 status, adjuvant chemotherapy and endocrine
      therapy. Progesterone receptor expression was compared with (all causes) overall
      survival (OS), breast cancer-specific survival (BCSS) and disease-free survival
      (DFS). RESULTS: Overall survival was 71.0% and BCSS was 83.0% at median follow-up
      of 8.34 years. Absent PR expression was significantly associated with poorer
      prognosis for OS, BCSS and DFS (P<0.0001, log-rank), even within the ER-positive,
      LN-negative group (hazard ratio for BCSS 3.17, 95% CI 1.43-7.01) and was not
      influenced by endocrine therapy. Cox's regression analysis demonstrated that PR
      expression was an independent prognostic variable. CONCLUSION: Absence of PR
      expression is a powerful, independent prognostic variable in operable, primary
      breast cancer even in ER-positive, LN-negative patients receiving endocrine
      therapy. Absence of PR expression should be re-evaluated as a biomarker for poor
      prognosis in ER-positive breast cancer and such patients considered for
      additional systemic therapy.

PMID- 24300978
TI  - SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite
      disposition in patients with solid tumours.
AB  - BACKGROUND: Gemcitabine is used for the treatment of several solid tumours and
      exhibits high inter-individual pharmacokinetic variability. In this study, we
      explore possible predictive covariates on drug and metabolite disposition.
      METHODS: Forty patients were enrolled. Gemcitabine and dFdU concentrations in the
      plasma and dFdCTP concentrations in peripheral blood mononuclear cell were
      measured to 72 h post infusion, and pharmacokinetic parameters were estimated by
      nonlinear mixed-effects modelling. Patient-specific covariates were tested in
      model development. RESULTS: The pharmacokinetics of gemcitabine was best
      described by a two-compartment model with body surface area, age and NT5C2
      genotype as significant covariates. The pharmacokinetics of dFdU and dFdCTP were
      adequately described by three-compartment models. Creatinine clearance and
      cytidine deaminase genotype were significant covariates for dFdU
      pharmacokinetics. Rate of infusion of <25 mg m(-2) min(-1) and the presence of
      homozygous major allele for SLC28A3 (CC genotype) were each associated with an
      almost two-fold increase in the formation clearance of dFdCTP. CONCLUSION:
      Prolonged dFdCTP systemic exposures (>=72 h) were commonly observed. Infusion
      rate <25 mg m(-2) min(-1) and carriers for SLC28A3 variant were each associated
      with about two-fold higher dFdCTP formation clearance. The impacts of these
      covariates on treatment-related toxicity in more selected patient populations
      (that is, first-line treatment, single disease state and so on) are not yet
      clear.

PMID- 24300980
TI  - Guest editorial.

PMID- 24300979
TI  - Infection transmission and chronic disease models in the study of infection
      associated cancers.
AB  - In the last three decades, the appreciation of the role of infections in cancer
      aetiology has greatly expanded. Among the 13 million new cancer cases that
      occurred worldwide in 2008, around 2 million (16%) were attributable to
      infections. Concurrently, the approach to prevention of infection-related cancers
      is shifting from cancer control to infection control, for example, vaccination
      and the detection of infected individuals. In support of this change, the use of
      infection transmission models has entered the field of infection-related cancer
      epidemiology. These models are useful to understand the infection transmission
      processes, to estimate the key parameters that govern the spread of infection,
      and to project the potential impact of different preventive measures. However,
      the concepts, terminology, and methods used to study infection transmission are
      not yet well known in the domain of cancer epidemiology. This review aims to
      concisely illustrate the main principles of transmission dynamics, the basic
      structure of infection transmission models, and their use in combination with
      empirical data. We also briefly summarise models of carcinogenesis and discuss
      their specificities and possible integration with models of infection natural
      history. 

PMID- 24300981
TI  - Electrocorticography for seizure foci mapping in epilepsy surgery.
AB  - Patients with refractory focal epilepsy are thoroughly evaluated to identify an
      area of cortex that, if removed or disconnected, will lead to seizure freedom.
      Clinical semiology, neuroimaging, and scalp electroencephalogram provide an
      approximation of this area, whereas intracranial recording may permit a more
      precise localization and investigation of a selected cortical area.
      Intraoperative electrocorticography delineates the irritative zone, and subdural
      electrode implantation also permits cortical stimulation of eloquent areas.
      Intraoperative electrocorticography rarely captures spontaneous seizures and may
      be influenced by the effect of anesthetic drugs, and the correlation between
      complete resection of the irritative zone and postsurgical seizure outcome is
      unclear. Extraoperative monitoring is often superior to intraoperative
      electrocorticography but may also be associated with more risk of adverse events.
      Further development of ultrahigh-density electrode arrays is providing novel
      insights into the role of microseizures and high-frequency oscillations on
      ictogenesis and epileptogenesis.

PMID- 24300982
TI  - Intraoperative neurophysiologic sensorimotor mapping and monitoring in
      supratentorial surgery.
AB  - It has been shown that aggressive removal of gliomas improves survival and the
      quality of life in both adults and children. Conversely, there is a strong
      correlation between incomplete resection of an epileptic focus and poor seizure
      control outcome in epilepsy surgery. Thus, it is no surprise that maximal
      resection of supratentorial lesions remains a priority in neurologic surgery. In
      many circumstances, this is difficult to achieve because of the close proximity
      of functionally eloquent regions. As a consequence, accurate identification of
      the latter is imperative to reliably identify safe boundaries for resection and
      to expand them as much as possible, while preserving neurologic function. Along
      these lines, preservation of sensorimotor function, with significant impact on
      postoperative outcome and quality of life, remains essential as achieving maximal
      resection. Although there is a wide range of methods that could be used for
      functional sensorimotor mapping, intraoperative neurophysiologic techniques are
      still considered by many to be the "gold standard." This article provides a
      detailed overview of these techniques, their principles, and several alternative
      methodologies. Although the overview directly reflects the current practice at
      our institution, it also shows the temporal evolution of the major motor mapping
      methods, relating them to all significant contributions made over the years by
      different experts in the field. I have tried to exemplify the relevant points of
      these techniques by using as many pictures and clinical examples as possible.

PMID- 24300983
TI  - Intraoperative functional cortical mapping of language.
AB  - Intraoperative neurophysiologic monitoring endeavors to preserve the integrity of
      the nervous system at a time of potential risk. The examination of language
      function in the operative setting is a unique task that requires a detailed and
      systematic approach to be carried out efficiently and reliably in this dynamic
      environment. In this review, we detail the technique used to identify eloquent
      language cortex during awake craniotomy. This technique requires a coordinated
      effort to testing, which is reliant on preoperative assessment and structured
      approach to functional cortical mapping by the surgical, anesthetic, and
      neurophysiology teams. Despite the intricate nature of this modality of testing,
      the accurate identification of language areas facilitates neurosurgeries for
      tumor and focal epilepsy syndromes in the dominant cerebral hemisphere, which
      depend on maximal margins of resection for best outcomes.

PMID- 24300984
TI  - Brainstem mapping.
AB  - The complex neuroanatomy of the brainstem and the additional distortion incurred
      by intrinsic lesions have previously discouraged aggressive neurosurgical
      procedures. Safe access to the brainstem and complete lesionectomy has been
      thwarted by considerable perioperative risk. Brainstem mapping has established
      itself as one of the means by which modern neurosurgery can improve surgical
      outcome while decreasing morbidity. It involves the use of neurophysiologic
      techniques for the identification of critical structures, such as the cranial
      motor nuclei and their nerves, and the corticobulbar and corticospinal tracts at
      different stages of the operation. Familiarity with these techniques can map a
      safe corridor toward a brainstem lesion and guide the surgeon during the
      resection. By means of reviewing the available literature, we discuss the
      anatomic, pathophysiologic, technical, and interpretational aspects of brainstem
      mapping and elaborate on its indications, limitations, and future directions.

PMID- 24300985
TI  - Spinal cord mapping.

PMID- 24300986
TI  - Intraoperative mapping of roots, plexuses, and nerves.
AB  - The use of intraoperative mapping of neural structures has come to be an
      indispensable technique to prevent or minimize postoperative morbidity. In this
      article, I briefly mention its use in mapping nerve roots, plexuses, and
      peripheral nerves. The reader may find some mention of monitoring techniques,
      too, as monitoring and mapping are seldom done separately. I include the
      technical details of different mapping modalities, relevant anatomy, and clinical
      applications, as appropriate.

PMID- 24300987
TI  - Carotid endarterectomies: who are the candidates at risk?
AB  - ABSTRACT OF REVIEWED ARTICLE: Predictors of clamp-induced electroencephalographic
      changes during carotid endarterectomies.Simon MV, Chiappa KH, Kilbride RD,
      Rordorf GA, Cambria RP, et al.J Clin Neurophysiol 2012t;29:462-467. OBJECTIVE:
      Electroencephalograms detect clamp-induced cerebral ischemia during carotid
      endarterectomy, and thus impact management and minimize the risk of perioperative
      stroke. We hypothesized that age, preoperative neurologic symptoms, >=70%
      contralateral carotid, and bilateral vertebral stenosis increase the probability
      of clamp-induced electroencephalogram changes, whereas >=70% unilateral carotid
      stenosis does not. METHODS: This is an observational cohort study of 299 patients
      who underwent carotid endarterectomy with electroencephalogram monitoring at a
      single large urban academic medical center in 2009. Univariate and multivariate
      logistic regression analyses were used. RESULTS: Seventy percent or greater
      ipsilateral carotid stenosis decreases the odds of clamp-induced neurophysiologic
      dysfunction (odds ratio = 0.43, 95% confidence interval [0.18-0.99], P = 0.04)
      after adjustment for symptomatic status, degree contralateral carotid or
      vertebral stenosis, and age. Preoperative neurologic symptoms, >=70%
      contralateral carotid stenosis, and bilateral extracranial vertebral stenosis
      independently increase these odds (odds ratio 2.62, 95% confidence interval [1.32
      5.18], P = 0.005; odds ratio 2.84, 95% confidence interval [1.27-6.34], P = 0.01;
      and odds ratio 3.58, 95% confidence interval [1.02-12.53], P = 0.04,
      respectively), after adjustment for the other factors. Age >=70 years has no
      significant impact. CONCLUSIONS: Preoperative neurologic symptoms, >=70%
      contralateral carotid, and bilateral vertebral stenosis increase the probability
      of clamp-induced ischemia as detected by intraoperative electroencephalogram,
      whereas >=70% ipsilateral carotid stenosis decreases it.

PMID- 24300988
TI  - Intraoperative monitoring: do you know where your neurophysiologist is?
AB  - OBJECTIVE: The professional practice of intraoperative monitoring has evolved
      over the past 30 years. This report describes the field's current state and how
      site of service affects practice. METHODS: A survey queried American Academy of
      Neurology intraoperative monitoringneurologist members about their intraoperative
      monitoring volume, case type, duration, numbers of simultaneous cases, and
      location of the monitoring physician. RESULTS: Physicians located locally
      typically monitored fewer cases annually and simultaneously compared with
      physicians who monitored from remote locations. Physicians at remote locations
      monitored proportionally more spine procedures, whereas physicians who monitored
      locally monitored more intracranial procedures and a greater variety of cases.
      CONCLUSIONS: The remote monitoring practice model is different from local models
      in annual volume, simultaneous cases, work per case, and types of cases.

PMID- 24300989
TI  - Simultaneous direct cortical motor evoked potential monitoring and subcortical
      mapping for motor pathway preservation during brain tumor surgery: is it useful?
AB  - ABSTRACT OF REVIEWED ARTICLE: The warning-sign hierarchy between quantitative
      subcortical motor mapping and continuous motor evoked potential monitoring during
      resection of supratentorial brain tumors: clinical article.Seidel K, Beck J,
      Steiglitz L, Schucht P, Raabe A.J Neurosurg 2013; 118:287-296. OBJECTIVE: Mapping
      and monitoring are believed to provide an early warning sign to determine when to
      stop tumor removal to avoid mechanical damage to the corticospinal tract (CST).
      The objective of this study was to systematically compare subcortical monopolar
      stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor
      evoked potential (MEP) monitoring signal abnormalities and to correlate both with
      new postoperative motor deficits. The authors sought to define a mapping
      threshold and DCS-MEP monitoring signal changes indicating a minimal safe
      distance from the CST. METHODS: A consecutive cohort of 100 patients underwent
      tumor surgery adjacent to the CST while simultaneous subcortical motor mapping
      and DCS-MEP monitoring were used. Evaluation was performed regarding the lowest
      subcortical mapping threshold (monopolar stimulation, train of 5 stimuli,
      interstimulus interval 4.0 milliseconds, pulse duration 500 microseconds) and
      signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor
      function was assessed 1 day after the surgery, at discharge, and at 3 months
      postoperatively. RESULTS: The lowest individual motor thresholds (MTs) were as
      follows (MT in mA, number of patients): >20 mA, n = 12; 11 to 20 mA, n = 13; 6 to
      10 mA, n = 20; 4 to 5 mA, n = 30; and 1 to 3 mA, n = 25. Direct cortical
      stimulation showed stable signals in 70 patients, unspecific changes in 18,
      irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months,
      5 patients had a postoperative new or worsened motor deficit (lowest mapping MT
      20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients, DCS-MEP monitoring
      alterations were documented (2 sudden irreversible threshold increases and 3
      sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic
      lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT: 1 mA, 3 mA, and 6
      mA; in the latter 2 cases, the resection continued after mapping and severe DCS
      MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1
      to 3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or
      showed unspecific reversible changes, and none had a permanent motor worsening at
      3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75%
      of patients with irreversible DCS-MEP loss had permanent motor deficits.
      CONCLUSIONS: Mapping should primarily guide tumor resection adjacent to the CST.
      Direct cortical stimulation-motor evoked potential is a useful predictor of
      deficits, but its value as a warning sign is limited because signal alterations
      were reversible in only approximately 60% of the present cases and
      irreversibility is a post hoc definition. The true safe mapping MT is lower than
      previously thought. The authors postulate a mapping MT of 1 mA or less where
      irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they
      recommend stopping tumor resection at an MT of 2 mA at the latest. The limited
      spatial and temporal coverage of contemporary mapping may increase error and may
      contribute to false, higher MTs.

PMID- 24300990
TI  - Syn-anti conformational switching in an ethane-bridged Co(II)bisporphyrin induced
      by external stimuli: effects of inter-macrocyclic interactions, axial ligation
      and chemical and electrochemical oxidations.
AB  - The syn-anti conformational switching has been demonstrated in the ethane-bridged
      dicobalt(II)bisporphyrin which is present in the syn-form only. The addition of
      either perylene or axial ligands to Co(II)(bisporphyrin) completely transforms
      the syn form into the anti because of strong pi-pi interaction and axial
      coordination, respectively. The complex undergoes four 1e-oxidations in CH2Cl2
      which are indicative of strong through space interactions between the two
      cofacial Co-porphyrins at 295 K. The first oxidation is a metal centered one and
      occurs at a potential much lower than that of the monomeric analog. However, the
      second oxidation, which is again metal centered, was at a significantly higher
      potential. The large difference between the first two oxidations, as observed
      here, is due to much stronger inter-porphyrin interactions. The step-wise
      oxidations have been performed both chemically and electro-chemically while the
      progress of the reactions was monitored by UV-visible and (1)H NMR spectroscopy.
      After 1e-oxidation, a very broad (1)H NMR signal results with increased
      difference between two meso resonances, which indicates that the two macrocycles
      are in the syn-form with lesser interplanar separation as also observed by DFT.
      However, 2e-oxidation results in the stabilization of the anti form. The addition
      of axial ligands to Co(II)(bisporphyrin) also completely transforms the syn form
      into the anti form. While additions of THF and I2/I(-) both result in the
      formation of five-coordinate complexes, Co(II) is oxidized to Co(III) in the case
      of the latter. However, additions of 1-methylimidazole, pyridine and pyrazine as
      axial ligands result in the formation of a six-coordinate complex in which Co(II)
      is spontaneously oxidized to Co(III) in air.

PMID- 24300991
TI  - Gold nanorods-bombesin conjugate as a potential targeted imaging agent for
      detection of breast cancer.
AB  - Photoacoustic imaging (PAI) is a hybrid biomedical imaging modality that offers
      both strong optical absorption contrast and high ultrasonic resolution. PAI is
      capable of in vivo molecular imaging, thus facilitating further molecular and
      cellular characterization of cancer. In this study, Gold nanorods (GNRs) were
      synthesized and coated with polyethyleneglycol (PEG). Then, the PEG-GNRs were
      conjugated with bombesin (BBN), a cancer seeking peptide, for production of a
      potential photoacoustic targeting imaging agent for detection of breast cancer.
      The optical property, biocompatibility, stability and in vitro/in vivo binding
      affinities of GNR-PEG-BBN for breast cancer cells were investigated. UV-vis
      spectroscopy confirmed the conjugation of bombesin with PEG-coated GNRs. The
      stability assessment proved high optical stability of GNR-PEG-BBN in human blood
      serum up to 12h. Cytotoxicity study showed biocompatibility of GNR-PEG-BBN
      conjugate. Molecular targeting ability was approved in cells over expressing
      gastrin-releasing peptide (GRP) receptor (breast cancer cell line) in comparison
      with cells that do not express GRP receptor (skin fibroblast cell line). The
      selective accumulation of GNR-PEG-BBN was demonstrated in breast tumor in
      comparison with unconjugated gold nanorods, following the intravenous
      administration of GNR-PEG-BBN to breast tumor-bearing mice. This study
      demonstrated the potential of GNR-PEG-BBN as a photoacoustic imaging agent that
      can provide improved specificity and sensitivity for breast cancer detection. 

PMID- 24300992
TI  - Biodegradation improvement of poly(3-hydroxy-butyrate) films by entomopathogenic
      fungi and UV-assisted surface functionalization.
AB  - Ultraviolet (UV)-assisted surface modification in the presence of oxygen was used
      as initial step to achieve controlled degradation of poly(3-hydroxy-butyrate),
      PHB, films by entomopathogenic fungi. Treated surfaces were investigated by
      surface analysis techniques (water contact angle, Fourier Transformed Infrared
      Spectroscopy in Attenuated Total Reflectance mode, X-ray Photoelectron
      Spectroscopy, Near-edge X-ray Absorption Fine Structure, Gel Permeation
      Chromatography, Optical Microscopy, Scanning Electron Microscopy, and weight
      loss). After the UV-assisted treatments, new carbonyl groups in new chemical
      environments were detected by XPS and NEXAFS spectroscopy. The oxidizing
      atmosphere did not allow the formation of CC bonds, indicating that Norrish Type
      II mechanism is suppressed during or by the treatments. The higher hydrophilicity
      and concentration of oxygenated functional groups at the surface of the treated
      films possibly improved the biodegradation of the films. It was observed a clear
      increase in the growth of this fungus when oxygenated groups were grafted on the
      polymers surfaces. This simple methodology can be used to improve and control the
      degradation rate of PHB films in applications that require a controllable
      degradation rate. 

PMID- 24300993
TI  - The chloroplast protein LTO1/AtVKOR is involved in the xanthophyll cycle and the
      acceleration of D1 protein degradation.
AB  - The thylakoid protein LTO1/AtVKOR-DsbA is recently found to be an oxidoreductase
      involved in disulfide bond formation and the assembly of photosystem II (PSII) in
      Arabidopsis thaliana. In this study, experimental evidence showed that LTO1
      deficiency caused severe photoinhibition which was related to the xanthophyll
      cycle and D1 protein degradation. The lto1-2 mutant was more sensitive to intense
      irradiance than wild type. When treated with different concentrations of
      dithiothreitol (DTT), an inhibitor of violaxanthin de-epoxidase (VDE) in the
      xanthophyll cycle, there was a larger reduction in NPQ in the wild type than in
      the lto1-2 mutant under high irradiance, indicating that lto1-2 had a lower
      sensitivity to DTT gradients than did the wild type. Zeaxanthin in the
      xanthophyll cycle, which participates in the thermal dissipation of excess
      absorbed light energy, was much less active in lto1-2 than in the wild type under
      intense light levels, and the de-epoxidation state of the xanthophyll cycle was
      consistent with the susceptibility of NPQ. Together these observations indicated
      that aggravated photoinhibition in lto1-2 was related to a reduction in
      xanthophyll cycle-associated energy dissipation. When D1 protein synthesis was
      suppressed by an inhibitor of chloroplast protein synthesis (streptomycin
      sulfate), the levels of D1 protein decreased more in the lto1-2 mutant than in
      the wild type when exposed to intense light levels, implying that a deficiency in
      LTO1 accelerated the degradation of D1 and thus affected D1 turnover. Transgenic
      complementation of plants with lto1-2 ultimately allowed for the recovery of the
      photoinhibition properties of leaves. 

PMID- 24300994
TI  - Effect of encapsulation in the anion receptor pocket of sub-domain IIA of human
      serum albumin on the modulation of pKa of warfarin and structurally similar
      acidic guests: a possible implication on biological activity.
AB  - Supramolecular and bio-supramolecular host assisted pKa shift of biologically
      relevant acidic guests, warfarin and coumarin 343, has been monitored using both
      steady-state and time resolved fluorescence spectroscopy. The anion receptors
      present in sub-domain IIA of human serum albumin (HSA) stabilize the anionic form
      of the guest and thereby shift pKa towards acidic range. On the other hand, the
      preferential binding of the neutral form of guests in the non-polar hydrophobic
      cavity of beta-cyclodextrin results in up-shifted pKa. This shifting of pKa of
      drugs like warfarin, etc., whose therapeutic activity depends on the position of
      the acid-base equilibrium in human system, is of great importance in
      pharmacokinetics. The release of the active form of such drugs from macrocyclic
      carrier and subsequent distribution through the carrier protein should depend on
      the modulation of the overall pKa window brought about by the encapsulation in
      these hosts. Present work also suggests that properly optimized encapsulation in
      appropriate receptor pocket can enhance the bioavailability of drugs. This work
      also opens up the possibility to use HSA as encapsulator, instead of traditional
      cyclodextrins or other polymeric hosts, since such system may overcome toxicity
      as well as biocompatibility issues. 

PMID- 24300995
TI  - DHPLC and MS studies of a photoinduced intrastrand cross-link in DNA labeled with
      5-bromo-2'-deoxyuridine.
AB  - It is well known that the replacement of thymidine with 5-bromo-2'-deoxyuridine
      (BrdU) in DNA sensitizes it to UVB light. Irradiation of a biopolymer substituted
      in such a way leads to manifold kinds of DNA damage, such as intrastrand cross
      links, single- and double-strand breaks or alkali-labile sites that were studied
      in the past with a broad spectrum of analytical methods. Here, we demonstrate
      that completely denaturing high-performance liquid chromatography (DHPLC),
      underestimated so far in DNA damage studies, could act as an inexpensive, and
      high-resolution substitute for the commonly employed gel electrophoresis. We
      report on the DHPLC/mass spectrometry (MS) analyses of photolytes obtained with
      the UV irradiation of aqueous solutions containing 40 base pairs of a long,
      double-stranded oligonucleotide labeled with BrdU in one of its strands. The UV
      product was detected by HPLC at a temperature of 70 degrees C. Subsequent MS
      analysis with electrospray ionization (ESI-MS) of the photolyte, enzymatic
      digestion of the irradiated material and HPLC and MS analysis (LC-MS) of the
      digest demonstrated unequivocally that an intrastrand covalent dimer, involving
      adenine and uracil, is formed in the irradiated system. 

PMID- 24300996
TI  - Perinaphthenone phototransformation in a model of leaf epicuticular waxes.
AB  - Perinaphthenone (1H-phenalen-1-one, PN) is a reference photosensitizer producing
      singlet oxygen with a quantum yield close to one in a large variety of solvents.
      It is also the basic structure of a class of phototoxic phytoalexins. In this
      work, the PN photoreactivity was studied for the first time in a paraffinic wax,
      used as model of leaf epicuticular waxes. The PN photodegradation was monitored
      by UV-Vis spectroscopy. The triplet excited state, singlet oxygen and the
      hydroxyperinaphthenyl radical were detected by diffuse reflectance laser flash
      photolysis, near infrared phosphorescence and by EPR spectroscopy, respectively.
      The PN phototransformation was found to be fivefold faster in the wax than in n
      heptane under steady-state irradiation. The hydroxyperinaphthenyl radical
      formation was observed in aerated irradiated paraffin wax while in n-heptane
      solution the radical was observed only in the absence of oxygen. These results
      show that under continuous irradiation, PN is much more easily phototransformed
      in a solid environment than in solution. Several photoproducts were identified,
      in particular phenalanone, PN dimers, and oxidized PN-alkanes adducts. Finally,
      when pyrethrum extract is added into the wax along with PN, the
      hydroxyperinaphthenyl radical concentration was increased by a factor of 2.4.
      Such photochemical reactions may occur when systemic pesticides enter the plant
      cuticle. 

PMID- 24300997
TI  - Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations
      against ROS-induced and UV-induced damage.
AB  - A method of panthenol-stabilized cerium dioxide nanoparticles synthesis was
      developed and their effect on the survival rate of human epidermoid cancer cells
      HEp-2 and diploid epithelial swine testicular cell line (ST-cells) under
      oxidative stress conditions induced by hydrogen peroxide introduction and UV
      irradiation was studied. The results obtained indicate that the use of panthenol
      as a stabilizer supposedly provides a substantial increase in the efficiency of
      protection. The degree of protection is determined by panthenol-to-ceria molar
      ratio. The combination of panthenol and nano-ceria protects biological objects
      under study from reactive oxygen species (ROS) and UV-irradiation more
      effectively than individual panthenol or ceria. The protective action of
      panthenol-stabilized cerium dioxide nanoparticles depends strongly on their
      composition and the means of their application. 

PMID- 24300998
TI  - Publication selection and the income elasticity of the value of a statistical
      life.
AB  - Estimates of the value of a statistical life (VSL) establish the price government
      agencies use to value fatality risks. Transferring these valuations to other
      populations often utilizes the income elasticity of the VSL, which typically draw
      on estimates from meta-analyses. Using a data set consisting of 101 estimates of
      the income elasticity of VSL from 14 previously reported meta-analyses, we find
      that after accounting for potential publication bias the income elasticity of
      value of a statistical life is clearly and robustly inelastic, with a value of
      approximately 0.25-0.63. There is also clear evidence of the importance of
      controlling for levels of risk, differential publication selection bias, and the
      greater income sensitivity of VSL from stated preference surveys. 

PMID- 24300999
TI  - In utero exposure to the Korean War and its long-term effects on socioeconomic
      and health outcomes.
AB  - Prenatal exposure to the disruptions caused by the Korean War (1950-1953)
      negatively affected the individual socioeconomic and health outcomes at older
      ages. The educational attainment, labor market performance, and other
      socioeconomic outcomes of the subjects of the 1951 birth cohort, who were in
      utero during the worst time of the war, were significantly lower in 1990 and in
      2000. The results of difference-in-difference estimations suggest that the
      magnitude of the negative cohort effect is significantly larger for individuals
      who were more seriously traumatized by the war. Whereas the 1950 male birth
      cohort exhibited significantly higher disability and mortality rates at older
      age, the health outcomes of females are unaffected by the war. Different aspects
      of human capital (e.g., health and cognitive skills) were impaired by in utero
      exposure to the war, depending on the stage of pregnancy when the negative shocks
      were experienced. 

PMID- 24301000
TI  - Cell cycle: Forming healthy attachments.

PMID- 24301001
TI  - Evaluation of neutron dose equivalent from the Mevion S250 proton accelerator:
      measurements and calculations.
AB  - Neutron production is of concern for proton therapy, especially for passive
      scattering proton beam delivery methods. The levels of neutron dose equivalent
      vary significantly with system design and treatment parameters. The purpose of
      this study was to examine neutron dose equivalent per therapeutic dose (H/D)
      around the Mevion S250 proton therapy system, a novel design of proton therapy
      systems. The benchmark comparisons between measurement and simulation were found
      to be within a factor of 2 for most cases. The H/D values were evaluated as a
      function of various parameters. The results showed that, at a standard reference
      condition (10 * 10 cm(2) field size, distance 1 m detector-to-isocenter lateral
      to the primary proton beam direction), the H/D values range from 0.72 to 3.37 mSv
      Gy(-1) for all configurations studied. The H/D values generally (1) decreased as
      the neutron detectors moved away from the isocenter, (2) decreased with
      increasing aperture field sizes, (3) increased with increasing angle from the
      initial beam axis and (4) were independent of treatment nozzle position. The H/D
      trends were consistent with other existing passive scattering proton accelerators
      reported in the literature.

PMID- 24301002
TI  - An introduction to the supplement 'A practical approach to the nutritional
      management of children with cerebral palsy'.

PMID- 24301003
TI  - Nutritional management of children with cerebral palsy.
AB  - Children with severe cerebral palsy and particularly those with oropharyngeal
      dysfunction are at risk of poor nutritional status. Determining the need and the
      mode of nutritional intervention is multifactorial and requires multiple
      methodologies. First-line treatment typically involves oral nutritional support
      for those children who are safe to consume an oral diet. Enteral tube feeding may
      need to be considered in children with undernutrition where poor weight gain
      continues despite oral nutritional support, or in those with oropharyngeal
      dysphagia and an unsafe swallow. Estimates for energy and protein requirements
      provide a starting point only, and ongoing assessment and monitoring is essential
      to ensure nutritional needs are being met, that complications are adequately
      managed and to avoid over or under feeding. 

PMID- 24301004
TI  - Psychosocial aspects of feeding children with neurodisability.
AB  - The psychosocial support needs of parents considering a gastrostomy feeding tube
      for their disabled child are often overlooked, yet there is a growing body of
      evidence that attests to the decisional conflicts parents, often mothers,
      experience. This may be in addition to the stress associated with feeding a
      disabled child. The support needs of families and caregivers should be assessed,
      including the values parents attach to oral and tube feeding. Structured support
      should be embedded within the care pathway and both professionals, and service
      users, with appropriate training should be identified to ensure parental
      information needs, and any emotional, practical and financial issues are
      addressed. 

PMID- 24301005
TI  - Nutritional management of children with cerebral palsy: a practical guide.

PMID- 24301006
TI  - Nutrition and growth in children with cerebral palsy: setting the scene.

PMID- 24301007
TI  - Assessment of growth and nutrition in children with cerebral palsy.
AB  - This manuscript provides an update on the assessment of growth and nutrition in
      children with cerebral palsy and children with similar neurodevelopmental
      disabilities. Topics include the assessment of linear growth using segmental
      measures, avoidance of commonly used tools to assess nutritional status in
      typically developing children that are not valid in this population of children
      and how to use other nutritional assessment tools that have been developed
      specific to this population of children. 

PMID- 24301008
TI  - Feeding children with cerebral palsy and swallowing difficulties.
AB  - Children with cerebral palsy (CP) are at risk for aspiration with oral feeding
      with potential pulmonary consequences, and commonly have reduced
      nutrition/hydration status and prolonged stressful meal times. There is
      considerable variability in the nature and severity of swallowing problems in
      these children whose needs change over time. Children with generalized severe
      motor impairment (for example, spastic quadriplegia) are likely to experience
      greater swallowing deficits than those with diplegia, but oropharyngeal dysphagia
      is prevalent even in children with mild CP. This review is focused on dysphagia
      in children with CP: types of deficits, clinical and instrumental evaluation,
      management decision making and evidence of effectiveness of interventions. 

PMID- 24301010
TI  - Establishment of equilibrium for the dominant lethal gene for Manx taillessness
      in cats.
AB  - An account is given of a model by which the dominant gene for Manx taillessness
      in cats is maintained at a stable equilibrium value in cat populations in spite
      of the homozygous condition being lethal. The model assumes that M-carrying sperm
      have a selective advantage during fertilization, and that M-carrying chromatids
      are selectively retained at the second maturation division. Estimates of
      fertilization parameters differed significantly from the value 0.5, which is the
      expected value if selective fertilization is absent. 

PMID- 24301009
TI  - Formation of ordered biomolecular structures by the self-assembly of short
      peptides.
AB  - In nature, complex functional structures are formed by the self-assembly of
      biomolecules under mild conditions. Understanding the forces that control self
      assembly and mimicking this process in vitro will bring about major advances in
      the areas of materials science and nanotechnology. Among the available biological
      building blocks, peptides have several advantages as they present substantial
      diversity, their synthesis in large scale is straightforward, and they can easily
      be modified with biological and chemical entities(1,2). Several classes of
      designed peptides such as cyclic peptides, amphiphile peptides and peptide
      conjugates self-assemble into ordered structures in solution. Homoaromatic
      dipeptides, are a class of short self-assembled peptides that contain all the
      molecular information needed to form ordered structures such as nanotubes,
      spheres and fibrils(3-8). A large variety of these peptides is commercially
      available. This paper presents a procedure that leads to the formation of ordered
      structures by the self-assembly of homoaromatic peptides. The protocol requires
      only commercial reagents and basic laboratory equipment. In addition, the paper
      describes some of the methods available for the characterization of peptide-based
      assemblies. These methods include electron and atomic force microscopy and
      Fourier-Transform Infrared Spectroscopy (FT-IR). Moreover, the manuscript
      demonstrates the blending of peptides (coassembly) and the formation of a "beads
      on a string"-like structure by this process.(9) The protocols presented here can
      be adapted to other classes of peptides or biological building blocks and can
      potentially lead to the discovery of new peptide-based structures and to better
      control of their assembly. 

PMID- 24301011
TI  - Reversion of Texas male-sterile cytoplasm maize in culture to give fertile, T
      toxin resistant plants.
AB  - Plants carrying Texas male-sterile (Tms) cytoplasm are normally sensitive to
      Drechslera maydis T-toxin. Tissue cultures were initiated from immature embryos
      of maize carrying Tms-cytoplasm, and plants were regenerated after selection for
      resistance to T-toxin. Fertile, T-toxin resistant plants were obtained from the
      unselected control cultures as well as from the selected material. In addition,
      one regenerant from an unselected culture was fertile and T-toxin sensitive. The
      progeny of the regenerants showed the phenotype of the female parent with respect
      to pollen-fertility, and T-toxin resistance. The data are consistent with the
      heritable changes observed being the result of the expression of an altered
      mitochondrial genome. 

PMID- 24301012
TI  - Growth, feed efficiency and lifetime performance of crosses between lines
      selected for nursing ability and/or adult weight in mice.
AB  - Two populations of randombred of different origin (P and Q) containing eight
      lines (MP, WP, BP, CP, MQ, WQ, BQ and CQ) were used to evaluate the growth, feed
      efficiency and lifetime performance of females from eight pure lines and 16 F1
      crosses. Line comparisons within populations (P or Q) revealed that the heaviest
      line at days 21, 42 and 63 was W, followed by lines B, M and C in both
      populations, while the highest in feed efficiency between days 21 and 63 was line
      W, followed by lines B, M and C in population P, and was line B followed by lines
      W, M and C in population Q. Generally, average body weights and feed efficiencies
      of crosses within and between populations were similar to those of mid-parents.
      Selection produced line W superior to the line M in additive direct genetic
      effects on body weight and feed efficiency in each population, and line WP
      superior to line WQ in additive maternal genetic effects on body weights at days
      21, 42 and 63. In lifetime performance tests, total 20-day weight of litters
      produced by a dam during 200 days averaged from 442.7 g (WP) to 739.1 g (MP) for
      the eight lines. Lines M and W of populations P and Q generally did not differ in
      additive direct and maternal genetic effects on lifetime performance. Crosses
      excelled lines in the number of litters raised to weaning (5.44 vs. 5.25) and
      total 20-day litter weight per dam during 200 days (648.5 vs. 589.3 g). For
      lifetime 20-day litter weight per group, crosses from unselected lines (C)
      exceeded crosses from lines selected for nursing ability (M), adult weight (W)
      and both traits (B). Crosses of lines from different populations showed a higher
      heterosis in lifetime performance than crosses of lines within populations.
      Heterosis in the number of litters raised to weaning, and total 20-day litter
      weight per dam was significant in crosses between lines CP and CQ, between lines
      WP and wQ, and between lines WP and mQ. Crosses CPCQ and CQCP had a highly
      persistent production during lifetime tests. 

PMID- 24301013
TI  - Combining ability analyses of stability parameters and forage yield in smooth
      bromegrass.
AB  - Twenty-one progenies of smooth bromegrass (Bromus inermis Leyss.) from a 7 X 7
      half diallel cross, with their parents, were evaluated for three years at four
      locations in Alberta for the genetic variation of stability in expression of
      their annual yield. The linear response and deviation from linear response for
      each genotype were the two stability parameters considered, together with mean
      performance in the evaluation of each genotype. Four high yielding genotypes,
      namely 12, 13, 16, and 26, had general adaptability, while genotype 23 was
      especially suited to a poor environment. Combining ability analysis showed that
      general combining ability (GCA) and specific combining ability (SCA) were both
      important in the expression of yield. Inheritance of linear regression was
      controlled predominantly by GCA whereas both GCA and SCA were equally important
      in the expression of deviation. The presence of a substantial proportion of
      variability due to the additive genetic component in the linear response suggests
      that it should be possible to exploit this fraction of variability in developing
      high yielding stable cultivars. 

PMID- 24301014
TI  - In vitro dissociation-recombination of malate dehydrogenase subunits in Corydalis
      solida.
AB  - Two allelic forms of NAD specific malate dehydrogenase were found in samples of a
      wild population of Corydalis solida. The dimeric nature and the origin of the
      heterodimeric form has been demonstrated by in vitro dissociation and
      recombination of the subunits detected by subsequent electrophoresis. The method
      is applicable for polyacrylamide gel electrophoresis of crude leaf extracts of
      individual MDH isozyme forms. 

PMID- 24301015
TI  - Fitness of a translocation homozygote in cage experiments with the onion fly,
      Hylemya antiqua (meigen).
AB  - In Hylemya antiqua, a stock homozygous for an autosomal reciprocal translocation
      was isolated using egg-hatch reduction and karyotype analysis. Sibling
      translocation homozygous (TT) and heterozygous (T+) females were compared in
      respect to egg production and longevity. In one full-sib (5 TT and 8 T+ females)
      significantly higher values for both parameters for T+ than for TT females were
      scored, in four others (a total of 35 TT and 28 T+ females) no significant
      differences were found. Cage experiments were started with populations composed
      of equal numbers of wild type flies (++) and translocation homozygotes. The
      frequencies of the different karyotypes in three successive, non-overlapping
      generations, did not suggest substantial differences in fitness between ++ and TT
      flies. Possible causes of a surplus of T+ individuals found in these experiments
      are discussed together with the usefulness of the translocation for genetic
      control of H. antiqua. 

PMID- 24301016
TI  - Potentiality of leaf sheath cells for regeneration of rice (Oryza sativa L.)
      plants.
AB  - Regeneration of rice plantlets (Oryza sativa L.) from calli originated from leaf
      sheath cells was made possible. This was possible in tissues initially grown in
      media containing 2.4-D (2.4-dichlorophenoxyacetic acid) at low temperature and
      illumination. The slow growing tissues were subsequently subjected to growth
      conditions at an elevated temperature and higher illumination with addition of
      kinetin and IAA and without 2.4-D. The suitability of leaf sheath cells for
      protoplast technology is indicated by this success. 

PMID- 24301017
TI  - Further characterization of picloram-tolerant mutants of Nicotiana tabacum.
AB  - A genetic and preliminary biochemical analysis has been performed on four
      picloram-tolerant mutants of Nicotiana tabacum that were isolated from cell
      cultures. The four mutations define three distinct linkage groups. Mutant
      seedlings incorporate radioactively labeled picloram normally and do not modify
      or degrade the herbicide in a manner that alters its solubility characteristics. 

PMID- 24301018
TI  - Concurrent explanations can enhance visual decision making.
AB  - The verbalization of one's thoughts has been shown to impair judgment and
      decision making in some cases, particularly when targets are perceptual. This
      finding has been attributed to the fact that non-verbal processes are sometimes
      difficult to verbalize, which may cause a shift in processing that is maladaptive
      to the task. The study shows that concurrent written explanations can also
      enhance judgment and decision making in certain visual choice tasks. This finding
      suggests that the effect of verbalization on perceptual tasks is not dependent on
      whether the targets of the judgment are verbal or perceptual but rather on
      whether there is adequate vocabulary to execute the task and whether the task
      benefits from a more analytic approach. 

PMID- 24301019
TI  - Profiling of carbohydrate mixtures at unprecedented resolution using high
      precision 1H-13C chemical shift measurements and a reference library.
AB  - Complex mixtures of carbohydrates pose distinct challenges in routine and high
      throughput analysis, so that only a few carbohydrate components are routinely
      resolved and identified in biofluids, extracts, foods and other complex mixtures.
      Here, we conduct precise measurements of (1)H and (13)C anomeric chemical shifts
      to construct a reference library of specific carbohydrate signals with high
      resolution two-dimensional (1)H-(13)C NMR spectra. High-resolution
      multidimensional NMR spectra largely abolish resolution problems in carbohydrate
      analysis with state-of-the-art instrumentation. Accurate measurements of anomeric
      (1)H-(13)C chemical shifts at parts per billion precisions permit robust
      carbohydrate identification using a very limited number of instrument-independent
      reference values. 

PMID- 24301020
TI  - Ribosome profiling reveals features of normal and disease-associated
      mitochondrial translation.
AB  - Mitochondria are essential cellular organelles for generation of energy and their
      dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure
      marked by failure to thrive, gastrointestinal problems, lactic acidosis and early
      lethality. Disease-associated mitochondrial mutations often affect components of
      the mitochondrial translation machinery. Here we perform ribosome profiling to
      measure mitochondrial translation at nucleotide resolution. Using a protocol
      optimized for the retrieval of mitochondrial ribosome protected fragments (RPFs)
      we show that the size distribution of wild-type mitochondrial RPFs follows a
      bimodal distribution peaking at 27 and 33 nucleotides, which is distinct from the
      30-nucleotide peak of nuclear RPFs. Their cross-correlation suggests generation
      of mitochondrial RPFs during ribosome progression. In contrast, RPFs from patient
      derived mitochondria mutated in tRNA-Tryptophan are centered on tryptophan codons
      and reduced downstream, indicating ribosome stalling. Intriguingly, long RPFs are
      enriched in mutated mitochondria, suggesting they characterize stalled ribosomes.
      Our findings provide the first model for translation in wild-type and disease
      triggering mitochondria. 

PMID- 24301021
TI  - Acid growth effects in maize roots: Evidence for a link between auxin-economy and
      proton extrusion in the control of root growth.
AB  - The role of proton excretion in the growth of apical segments of maize roots has
      been examined. Growth is stimulated by acidic buffers and inhibited by neutral
      buffers. Organic buffers such as 2[N-morpholino] ethane sulphonic acid (MES) - 2
      amino-2-(hydroxymethyl)propane-1,3 diol (Tris) are more effective than phosphate
      buffers in inhibiting growth. Fusicoccin(FC)-induced growth is also inhibited by
      neutral buffers. The antiauxins 4-chlorophenoxyisobutyric acid (PCIB) and 2
      (naphthylmethylthio) propionic acid (NMSP) promote growth and H(+)-excretion over
      short time periods; this growth is also inhibited by neutral buffers. We conclude
      that growth of maize roots requires proton extrusion and that regulation of root
      growth by indol-3yl-acetic acid (IAA) may be mediated by control of this proton
      extrusion. 

PMID- 24301022
TI  - Energy-dependent phases of the circadian clock and the clock-controlled leaf
      movement in Phaseolus coccineus L.
AB  - The energy requirements of the various phases of the circadian clock in the
      laminar pulvini cells of primary leaves of Phaseolus coccineus L. were
      investigated using 4-h pulses of NaCN (5 mM) and NaN3 (1 mM). The induced phase
      shifts were calculated from the timing of the subjective night position during
      the third cycle after the treatment. Both inhibitors produce advances during
      phases which are correlated with the upward movement of the leaf (ca. 0-12 h
      after the maximum of the subjective night position) and during phases which are
      correlated with the downward movement of the leaf (ca. 20-28 h after the maximum
      of the subjective night position). Maximal advances are induced during the phase
      which is correlated with the maximum of the subjective night position (hour 0),
      whereas during phases which are correlated with the subjective day position (ca.
      12-20 h after the maximum of the subjective night position) the inhibitors have
      no effect or induce only small advances. These results demonstrate that the part
      of the circadian cycle which, according to Bunning's tension-relaxation model of
      the circadian clock, is characterized by features of relaxation, represents a
      sequence of phases with decreasing energy requirement, whereas the tension part
      of the circadian cycle represents a sequence of phases with increasing energy
      requirement. The energy requirement for changing and maintaining the leaf
      positions was investigated by continuously offering NaCN, NaN3, and dinitrophenol
      (DNP) to leaves with intact and half (flexor cut away) pulvini. The substances
      inhibit in both pulvini the upward movement or induce a downward movement,
      depending on the leaf position, when the transfer to the inhibitor solution takes
      place. These results give evidence that the movement of intact pulvini reflects
      the turgor (volume) state of the extensor cells and that the increase of turgor
      (volume) and high turgor (volume) state requires more energy than the decrease of
      turgor (volume) or low turgor (small volume) state. Therefore, the time course of
      the energy requirements of the circadian clock and the clock-controlled turgor
      (volume states or leaf movement) is out of phase during a circadian cycle.
      Consequently the reaction of the clock-controlled leaf movement to the reduced
      energy supply can mask the clock behavior in pulse and step experiments. The
      phase response curves towards CN(-) and N 3 (-) reflect the time course of the
      CN(-)-induced membrane depolarizations (the energy requirement of the
      electrogenic pump) in extensor cells of the pulvinus (Freudling et al. (1980),
      Plant Physiol. 65, 966-968), and both are out of phase with the time course of
      the energy requirement of the turgor. Consequently it is hypothesized that in
      Phaseolus advances are due to membrane depolarization and that at least in this
      organism electric properties of the plasmalemma are essentially involved in the
      mechanism of the circadian clock. 

PMID- 24301023
TI  - Glyoxylate decreases the oxygen sensitivity of nitrogenase activity and
      photosynthesis in the cyanobacterium Anabaena cylindrica.
AB  - Raising the pO2 reduced nitrogenase activity (C2H2 reduction) of Anabaena
      cylindrica for both glyoxylate-treated (5 mM) and untreated cells. The
      stimulation caused by glyoxylate, however, increased with increases of pO2 from 2
      to 99 kPa. As the pO2 increased the net CO2 fixation was lowered (Warburg effect)
      while the CO2 compensation point increased. Glyoxylate partly relieved this
      sensitivity of net photosynthesis to oxygen and reduced the compensation point
      considerably. The cells used were preincubated in the dark to exhaust
      photosynthetic pools. A more pronounced reduction in sensitivity of nitrogenase
      to oxygen for glyoxylate-treated cells was evident when a preincubation in air
      with reduced pCO2 (13 MUl l(-1)) was used. This was, however, not evident until
      after a 10-h incubation in air. Before this point 2 kPa O2 sustained the highest
      nitrogenase activity. Addition of 0.5 and 5 mM of HCO 3 (-) to Anabaena cultures
      preincubated at low CO2 levels (29 MUl l(-1)) abolished the stimulatory effect of
      glyoxylate on the nitrogenase. Thus, the results sustain the suggestion that
      glyoxylate may act as an inhibitor of photorespiratory activities in
      cyanobacteria and can be used as a means of increasing their nitrogen and CO2
      fixation capacities. 

PMID- 24301024
TI  - The compartmentation of carboxylating and decarboxylating enzymes in guard cell
      protoplasts.
AB  - Guard cell and mesophyll cell protoplasts of Vicia faba L. were purified and
      separated into cytoplasmic and plastid fractions by a selective silicone-oil
      filtration. Before fractionation, the protoplasts were ruptured by a low speed
      centrifugation through a narrow-aperture nylon net placed in a plastic vial. This
      protoplast homogenation and subsequently the silicone-oil fractionation offer the
      possibility of investigating the comparatmentation of the enzymatic carboxylating
      (ribulose bisphosphate carboxylase EC 4.1.1.39, phosphoenolpyruvate carboxylase
      EC 4.1.1.31, NAD(+) and NADP(+) linked malate dehydrogenase EC 1.1.1.37) and
      decarboxylating pathways of malic (malic enzyme EC 1.1.1.40, phosphoenolpyruvate
      carboxykinase EC 4.1.1.32, pyruvate orthophosphate dikinase EC 2.7.9.1) which
      occur during the swelling and shrinking of the guard cell protoplasts. A model is
      proposed which describes the transport processes of malic acid during the starch
      malate balance as correlated to the volume changes of the protoplasts. As the
      enzymes and their compartmentation in the guard cell protoplasts seem to be
      consistent with those of crassulacean acid metabolism (CAM) plants, the
      metabolism of stomata and of CAM cells is compared. 

PMID- 24301025
TI  - High electric field effects on the cell membranes of Halicystis parvula : A
      charge pulse study.
AB  - The electrical breakdown behavior of the giant algal cell Halicystis parvula was
      studied in order to predict the optimum conditions for electrically induced cell
      to-cell fusion. Using the charge pulse technique, the membranes were charged at
      different pulse lengths to the maximum voltage Vc. Because of a reversible, high
      conductance state of the membrane (electrical breakdown), it was not possible to
      exceed the critical membrane breakdown potential. The breakdown voltage exhibited
      a strong dependence on the charging time (pulse length) between 10 MUs and 100
      MUs. Below 10 MUs the breakdown voltage of the two membranes, tonoplast and
      plasmalemma, assumed a constant value of about 1.9 V, whereas above a pulse
      length of about 100 MUs the breakdown voltage was nearly constant with a value of
      about 0.6 V. The extreme values for the breakdown voltage at very short and at
      very long charging times agree fairly well with results which have been obtained
      on cells of Valonia utricularis and planar lipid bilayer membranes. However, the
      pulse length dependence of the breakdown voltage was found to be quite different
      in H. parvula. In addition, the membrane conductance increase during breakdown in
      H. parvula cells is much more pronounced than in membranes of V. utricularis, but
      similar to lipid bilayer membranes. From this result it is suggested that the
      membrane structure of H. parvula is quite different from V. utricularis (larger
      lipid domains). 

PMID- 24301026
TI  - Daily changes in nitrate influx, efflux and metabolism in maize and pearl millet.
AB  - Maize (Zea mays L.) and pearl millet (Pennisetum americanum (L.) Leeke) seedlings
      were exposed to [(15)N]nitrate for 1-h periods at eight times during a 24-h
      period (16-8 h light-dark for maize; 14-10 h for millet). Influx of
      [(15)N]nitrate as well as its reduction and translocation were determined during
      each period. The efflux of previously absorbed [(14)N]nitrate to the uptake
      solution was also estimated. No marked diurnal changes in [(14)N]nitrate efflux
      or [(15)N]nitrate influx were evident in maize. In contrast, [(14)N]nitrate
      efflux from millet increased and eventually exceeded [(15)N]nitrate influx during
      the late dark and early light periods, resulting in net nitrate efflux from the
      roots. The dissimilarity of their diurnal patterns indicates that influx and
      efflux are independently regulated. In both species, [(15)N]nitrate reduction and
      (15)N translocation to shoots were curtailed more by darkness than was
      [(15)N]nitrate influx. In the light, maize reduced 15% and millet 24% of the
      incoming [(15)N]nitrate. In darkness, reduction dropped to 11 and 17%,
      respectively. Since the accumulation of reduced-(15)N in shoots declined abruptly
      in darkness, whereas that in roots was little affected, it is suggested that in
      darkness [(15)N]nitrate reduction occurred primarily in roots. The decrease in
      nitrate uptake and reduction in darkness was not related to efflux, which
      remained constant in maize and did not respond immediately to darkness in pearl
      millet. 

PMID- 24301027
TI  - Control by phytochrome of urate oxidase and allantoinase activities during
      peroxisome development in the cotyledons of mustard (Sinapis alba L.) seedlings.
AB  - The peroxisomal enzyme, urate oxidase (EC 1.7.3.3), and the next enzyme of the
      urate pathway, allantoinase (EC 3.5.2.5), demonstrate a lightmediated rise of
      activity in the cotyledons of mustard (Sinapis alba L.). The capacity of the
      peroxisomes for urate breakdown, marked by the time course of urate oxidase,
      develops distinctly later than the two other peroxisome functions (fatty acid
      breakdown, "glyoxysomal" function; glycolate breakdown, "leaf peroxisomal"
      function). The light effect on urate oxidase and allantoinase is mediated through
      the phytochrome system in all three seedling organs (cotyledons, hypocotyl,
      radicle), as revealed by induction/reversion experiments with red/far-red light
      pulses and continuous irradiation with far-red light (high irradiance reaction of
      phytochrome). Both enzyme activities can be induced by phytochrome in the
      seedling cotyledons only during a sensitive period of about 48 h prior to the
      actual light-mediated rise of activity, making it necessary to assume the
      existence of a long-lived intermediate ("transmitter") in the signal response
      chain connecting enzyme formation to the phytochrome system. Detailed kinetic
      investigation, designed to test whether urate oxidase and allantoinase are
      controlled by phytochrome via the same signal response chain (coordinate
      induction), revealed large differences between the two enzymes: (i) a different
      onset of the loss of reversibility of a red light induction by a far-red light
      pulse (=onset of transmitter formation=coupling point; 48 h/24 h after sowing for
      urate oxidase/allantoinase); (ii) a different onset of the response (=onset of
      competence for transmitter= starting point; 72 h/48 h); (iii) full loss of
      reversibility (=completion of transmitter formation) is reached at different
      times (independence point, 90 h/52 h). These differences show that phytochrome
      controls urate oxidase and allantoinase via separate signal response chains.
      While urate oxidase can be localized in the peroxisomal fraction isolated from
      crude organelle extracts of the cotyledons by density gradient centrifugation,
      most of the allantoinase activity found in the peroxisomal fraction did not
      appear to be an integral part of the peroxisome but originated presumably from
      adhering membrane fragments. 

PMID- 24301028
TI  - Uptake of [2-(14)C]abscisic acid and distribution of (14)C in apple embryos.
AB  - Pyrus malus L. var. Golden delicious embryos were incubated with (+/-)-[2
      (14)C]abscisic acid (ABA) (10(-5) M, 355 kBq MUmol(-1)). After incubations of
      various durations, the radioactivity was measured in whole embryos, cotyledons,
      and embryonic axes.With either 48-h or 16-d incubation periods, the uptake of
      [(14)C]ABA depended upon the mode of culture used. The lowest values corresponded
      to the absorption by the embryonic axis, the highest to the absorption by the
      distal parts of the two cotyledons. The cotyledons accumulated the main part of
      the radioactivity under all conditions. Dormant and almost completely after
      ripened embryos cultivated for 4 d showed no significant differences in the
      radioactivity uptake for identical modes of culture. There was a linear
      relationship between exogenous ABA concentrations (0.5 to 3.10(-5) M) and ABA
      uptake for embryos cultivated for 4 d with the distal parts of the cotyledons
      immersed in the medium. 

PMID- 24301029
TI  - Chloroplast transfer in Nicotiana based on metabolic complementation between
      irradiated and iodoacetate treated protoplasts.
AB  - Protoplasts of a light sensitive plastome mutant of Nicotiana tabacum (2 n=48)
      were irradiated and fused with iodoacetate-treated Nicotiana plumbaginifolia (2
      n=20) protoplasts. Treated parental protoplasts were unable to divide. Metabolic
      complementation, however, helped the recovery of interspecific fusion products
      which survived and formed calli. Altogether 40 clones were investigated. N.
      plumbaginifolia plants were obtained in 15 clones (38%), somatic hybrids in 23
      clones, and both types of regenerates were found in 2 clones. Irradiation
      therefore significantly increased the frequency of segregant formation with the
      non-irradiated N. plumbaginifolia nuclei (the frequency was 1.4% in the absence
      of irradiation). Regenerated plants in most cases (31 out of 34) contained
      chloroplasts from the irradiated parent. In 6 clones plants were obtained with
      both types of chloroplast. Thus, irradiated N. tabacum chloroplasts had an
      improved chance of dominating the heterokaryonderived cells, many of which
      contained N. plumbaginifolia nucleus. The system described should be generally
      applicable for the transfer of chloroplasts without the use of selectable genetic
      markers. 

PMID- 24301030
TI  - Stimulation of membrane-associated polysaccharide synthetases by a membrane
      potential in developing cotton fibers.
AB  - Conditions which induce a transmembrane electrical potential, positive with
      respect to the inside of membrane vesicles, result in a substantial (4-12-fold)
      stimulation of the activity of membrane-associated beta-glucan synthetases in a
      membrane preparation derived from the developing cotton (Gossypium hirsutum L.)
      fiber. Induction of electrical potentials which are negative with respect to the
      inside of the membrane vesicle results in little or no stimulation of beta-glucan
      synthesis. Those products whose synthesis is stimulated are mainly beta-1,3
      glucan, but there is also a considerable increase in beta-1,4-glucan. No alpha
      1,4-glucan (starch) was detected in the reaction products. A transmembrane pH
      gradient was found to have no effect on beta-glucan synthesis. The results
      indicate that a transmembrane electrical potential can influence, either directly
      or indirectly, the activity of membrane-associated polysaccharide synthetases. 

PMID- 24301031
TI  - A new electrical method for the determination of the cell membrane area in plant
      cells.
AB  - The membrane are of giant algal cells of Valonia utricularis was determined
      electrically by using the charge-pulse technique. The membrane was charged to low
      voltages between 2 and 20 mV by injecting charge pulses of defined amplitude and
      very short duration (about 100 ns). The injected charge was calculated by
      measuring the current increment via a potential drop across a 10 Omega resistance
      in the outer circuit and by considering the preselected charging time. The
      initial voltage across the membrane was calculated by extrapolation to time zero
      (=end of the charge pulse). From the values of the injected charge and the
      voltage built up initially across the membrane, the capacitance of the membrane
      could be calculated. Assuming that the specific capacity of the two membranes,
      tonoplast and plasmalemma, arranged in series was 0.5 MUF cm(-2), the membrane
      area could be derived from the membrane capacity. The electrically determined
      membrane area agrees with the geometrically determined one to within 10%. 

PMID- 24301032
TI  - The relationship between fruit growth and apical senescence in the G2 line of
      peas.
AB  - In the G2 line of peas (Pisum sativum L.), senescence of the shoot apex (which
      precedes leaf senescence) only occurs in long days (LD) though flowering is
      independent of photoperiod. It has been suggested that the photoperiodic control
      of senescence in G2 is mediated through different rates of seed growth. In LD
      seed growth is more rapid than in short days (SD) and this places a greater
      nutrient drain on the plant. In addition, more flowers develop into fruits in LD
      than in SD: 32% of flower buds abort in SD while almost none abort in LD.
      Senescence is associated with early seed growth and does not occur in deflowered
      or deseeded plants. Seed development is completed in 30d in LD while it takes 40d
      in SD, though the seed weights are similar. The maximum rate of fresh-weight gain
      of all the growing seeds of eight fruits on a plant in SD (1,440 mg/d) does not
      reach the maximum rate of weight gain of a similar fruit complement in LD (1,720
      mg/d). The appearance of senescence symptoms in the shoot apices of LD-grown G2
      plants occurs, however, prior to the time of the greatest rate of seed-weight
      gain. In LD, four fruits with a combined maximum growth rate of 1,250 mg/d are
      sufficient to cause the appearance of senescence symptoms. This is a lower
      combined seed growth rate than in SD where senescence does not occur. The seeds
      in up to 12 fruits can be growing at any time in SD with a combined maximum seed
      growth rate (1,660 mg/d), only slightly less than the maximum in LD, with no sign
      of senescence. It is concluded that the different rates of seed growth occasioned
      by different photoperiods bear no relation to senescence. However, photoperiod
      does alter the spatial relationship of the shoot apex and the filling fruits. In
      LD apical growth becomes slower as fruiting proceeds so that the distance between
      the filling fruits and the apex is decreased to only two nodes while in SD,
      because of the delayed fruit development compared to LD, the spatial separation
      between the fruits and the shoot apex is nine nodes. Even if the growth rate of
      the plant had remained constant in LD it is calculated that an equivalent fruit
      complement would still be located three nodes further from the apex in SD than in
      LD. This increased spatial separation of fruits and apex in SD compared to LD
      probably alters the source/sink distribution of photosynthate and leaf derived
      hormones so that larger amounts are available to the apex in SD than LD. Also any
      "senescence factor" exported from fruits is less likely to reach the apex in SD.
      In continuously deflorated plants of G2 the two uppermost expanded stipules
      enclose the apex in SD while in LD they open out. The effect is reversible. Thus
      photoperiod probably affects the apex and its growth, directly, i.e. independent
      of fruit development, and this is accentuated by the differing spatial
      relationships of the apex and fruits resulting from different fruit growth rates
      under the different photoperiodic conditions. 

PMID- 24301033
TI  - Activities of some enzymes of lignin formation in reaction wood of Thuja
      orientalis, Metasequoia glyptostroboides and Robinia pseudoacacia.
AB  - The activities of the following five enzymes which are involved in the formation
      of lignin have been compared in reaction wood and in opposite wood: phenylalanine
      ammonia lyase (EC 4.3.1.5), caffeate 3-O-methyltransferase (EC 2.1.1.-), p
      hydroxycinnamate: CoA ligase (EC 6.2.1.12), cinnamyl alcohol dehydrogenase (EC
      1.1.1.-) and peroxidase (EC 1.11.1.7). The activities of the four first-named
      enzymes in the compression wood of Thuja orientalis L. and Metasequoia
      glyptostroboides Hu et Cheng were 2.8+/-1.4-fold and 2.6+/-1.5-fold higher than
      those in opposite wood, respectively, whereas peroxidase had the same level of
      activity in either type of wood. On the other hand, no differences were observed
      in the activities of the five enzymes between tension and opposite woods of
      Robinia pseudoacacia L. These findings are well in accord with the chemical
      structure of lignin in the compression and tension woods of the three species
      studied: high content of lignin rich in condensed units in compression wood, and
      little difference in lignin between tension and opposite woods. 

PMID- 24301034
TI  - The involvement of phytochrome in controlling chlorophyll and 5-aminolevulinate
      formation in a gymnosperm seedling (Pinus sylvestris).
AB  - Chlorophyll a (Chl a) accumulation in the cotyledons of Scots pine seedlings
      (Pinus sylvestris L.) is much higher in the light than in darkness where it
      ceases 6 days after germination. When these darkgrown seedlings are treated with
      continuous white light (3,500 lx) a 3 h lag phase appears before Chl a
      accumulation is resumed. The lag phase can be eliminated by pretreating the
      seedlings with 7 h of weak red light (0.14 Wm(-2)) or with 14 red light pulses
      separated by relatively short dark periods (<100 min). The effect of 15s red
      light pulses can be fully reversed by 1 min far-red light pulses. This
      reversibility is lost within 2 min. In addition, the amount of Chl a formed
      within 27 h of continuous red light is considerably reduced by the simultaneous
      application of far-red (RG 9) light. It is concluded that phytochrome (Pfr) is
      required not only for the elimination of the lagphase but also to maintain a high
      rate of Chl a accumulation in continuous light. Since accumulation of 5
      aminolevulinate (ALA) responds in the same manner as Chl a accumulation to a red
      light pretreatment it is further concluded that ALA formation is the point where
      phytochrome regulates Chl biosynthesis in continuous light. No correlation has
      been found between ALA and Chl a formation in darkness. This indicates that in a
      darkgrown pine seedling ALA formation is not rate limiting for Chl a
      accumulation. 

PMID- 24301035
TI  - The estimation of phenylalanine ammonia-lyase (PAL) activity in intact cells of
      higher plant tissue : III. Specificity of (3)H-release from L-[2,3
      (3)H]phenylalanine and precautions in application of the assay to various
      tissues.
AB  - A previously described procedure for the estimation of relative activities of
      phenylalanine ammonia-lyase (EC 4.3.1.5) in intact plant cells (Amrhein et al.
      (1976) Planta 131, 33-40) was reexamined for its specificity and its
      applicability to various tissues. In buckwheat hypocotyl segments (3)H is
      stereospecifically released from the pro-3S-position of L-[2,3-(3)H]phenylalanine
      and is thus due to phenylalanine ammonia-lyase activity. In buck wheat and
      sunflower leaf disks, however, (3)H release occurs from both the 2- and 3
      positions of the labeled substrate and can only partially be attributed to
      phenylalanine ammonia-lyase activity. 

PMID- 24301036
TI  - Enhanced expression of a distinct plastid DNA region in mustard seedlings by
      continuous far-red light.
AB  - Fragments of chloroplast DNA from mustard (Sinapis alba L.) seedlings, generated
      by the restriction endonuclease Eco RI, were used to assess the frequency of
      complementary sequences in mustard RNA by DNA/RNA hybridization. A pronounced
      increase in hybridization to a single DNA fragment was found with RNA from
      seedlings irradiated with continuous far-red light, compared to RNA from dark
      grown seedlings. 

PMID- 24301037
TI  - Preparation and characterization of Au nanoparticles capped with
      mercaptocarboranyl clusters.
AB  - The preparation of 3-4 nm and 10 nm gold nanoparticles capped with neutral
      carborane-based mercaptocarboranes, via two different preparative routes, is
      reported. The resulting boron-enriched nanomaterials exhibit complete
      dispersibility in water, opening the way for the use of these monolayer protected
      clusters (MPCs) in medical applications, such as boron neutron capture therapy
      (BNCT). These newly prepared MPCs have been characterized by FTIR, (1)H and (11)B
      NMR spectroscopy, UV-visible, centrifugal particle sizing (CPS), and, in some
      cases, inductively coupled plasma atomic emission spectrometry (ICP-AES). Water
      dispersibility exhibited by these MPCs allowed the study of the cellular uptake
      by HeLa cells. 

PMID- 24301039
TI  - Achievement and identity in college-age vs. adult women students.
AB  - This study tested a developmental hypothesis with respect to Fear of Success
      (FOS), Identity Status, and the relationship between the two. Forty college
      students, equally divided between regular college-age women (18-23) and adult
      college women (over age 30), were given a multiple-choice and a projective
      measure of FOS; they were then interviewed regarding exploration and commitment
      in five content areas: vocation, family vs. career priority, politics, religion,
      and sex roles. The hypothesis that the adult students would exhibit less FOS than
      their college-age counterparts was confirmed with both measures of FOS. Chi
      square analysis also revealed that a significantly higher proportion of the adult
      students was classified as identity-achieved and a lower proportion as identity
      diffuse than the college-age students. The influence of life experience on the
      relationship between FOS and each identity status could not be tested due to an
      insufficient number of identity achievers in the college-age subsample; when the
      relationship of FOS to identity status was examined for the total sample,
      however, foreclosures and achievers manifested significantly less FOS than
      diffusions and moratoriums. 

PMID- 24301040
TI  - Antecedents of collegiate drinking.
AB  - A model designed to explain variations in the use of alcohol among undergraduates
      draws together three categories of variables: (1) sociocultural-race, sex, and
      population of student's hometown; (2) familial characteristics-father's
      occupation, parents' marital status, and closeness to a problem drinker; and (3)
      the onset of student drinking-age at first drinking and extent of drinking at its
      onset. A 10% random sample was drawn from the undergraduate students enrolled in
      two state-supported universities in the southeastern U.S. The present analysis
      focuses on 856 nonmarried, full-time undergraduate students. Overall, the
      findings show that race, degree of closeness to a problem-drinker, age at the
      onset of drinking, and its extent markedly influence the level of alcohol
      consumption among undergraduates. The strongest overall predictor of
      undergraduate drinking is the extent of adolescent consumption. 

PMID- 24301038
TI  - IL-12 secretion by Langerhans cells stimulated with Candida skin test reagent is
      mediated by dectin-1 in some healthy individuals.
AB  - OBJECTIVE: Our group and others have shown that serial intra-lesional injections
      of common warts with skin testing reagents such as Candida, mumps and
      Trichophyton are effective in regressing injected and non-injected warts. Anti
      HPV T-cell responses appear to be induced. The goal of this study was to
      understand the mechanisms of how Candida skin testing reagent enhances immune
      responses. METHODS: The following immunological features were studied to
      understand how Candida induces immune responses in healthy subjects: (1)
      proliferative capacity of T-cells upon exposure to Candida through monocyte
      derived human Langerhans cells (LCs) measured using alamarBlue, (2) cytokine (IL
      1beta, IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN-gamma, and TNF- expression
      upon Candida stimulation of LCs by quantitative reverse transcription (qRT)-PCR
      and cytokine secretion by ELISA, (3) expression of pattern recognition receptors
      (PRRs) known to associate with Candida albicans (DC-SIGN, dectin-1, dectin-2,
      galectin-3, mincle, mannose receptor, Toll-like receptors 1, 2, 4, 6, and 9) on
      LCs by qRT-PCR, (4) role of dectin-1 in IL-12 production by antibody blocking,
      and (5) induction of Th1, Th2, and/or Th17 responses by intracellular cytokine
      staining of CD4 cells exposed to Candida pulsed LCs for IFN-gamma, IL-4, and IL
      17A. RESULTS: T-cell proliferation upon stimulation with Candida-pulsed LCs was
      significantly higher compared to proliferation in the absence of Candida
      (p=0.004). The most frequently expressed cytokine in stimulated LCs was IL-12p40
      mRNA, and IL-12p40 and IL-12p70 were also detected at protein levels. All other
      cytokine mRNAs examined were detected in the following order of decreasing
      frequency: IL23Ap19, IFN-gamma, IL-1beta, IL-6, IL-8, and IL-10. LCs expressed
      all PRRs examined. Anti-dectin-1 inhibited IL-12p40 mRNA production upon Candida
      stimulation of LCs from some healthy subjects. IFN-gamma secretion was increased
      and IL-4 secretion was decreased in CD4 cells of a few healthy subjects, but IL
      17A was essentially unchanged upon Candida treatment. CONCLUSIONS: Proliferation
      of T-cells in a substantial majority of healthy subjects can be demonstrated with
      Candida stimulation. We show Th1 promotion and dectin-1 stimulation of LCs as
      potential mechanisms in some healthy subjects.

PMID- 24301041
TI  - Differentiating specialists and generalists within college students' social
      support networks.
AB  - In order to examine the relationships among social network structure, types of
      social support, and determinants of support satisfaction, an alternative method
      was used to score the Social Support Questionnaire (SSQ). Factor analysis
      procedures suggested that college students' (N=198) social networks consisted of
      four groups: nuclear family, other family, friends, and others. Satisfaction with
      support was positively related to the proportion of the network occupied by
      nuclear family and negatively related to the proportion of friends in the
      network. Evidence was found for the presence of both support specialists and
      support generalists in the networks of the college students. These results are
      discussed from a developmental perspective with attention to the implications for
      interventions. 

PMID- 24301042
TI  - Adolescents' fear of social consequences of academic success as a function of age
      and sex.
AB  - The Fear of Success Consequence Scale (FOSC) was used to assess adolescents'
      fears of potential social consequences of academic success in three dimensions,
      i.e., negative social reaction, positive peer reaction, and increased pressure
      and responsibility for continuous success. Subjects were 360 students in early
      adolescence (grades 7-9) and mid-adolescence (grades 10-12) in three urban
      British Columbia areas. Two hypotheses were supported: (1) that fear of academic
      success is higher among early adolescents than among mid-adolescents; (2) that
      girls generally have higher fear of academic success than do boys. Significant
      sex differences were found among early adolescents but not among mid-adolescents.
      While general sex differences were consistent with Horner's prediction, the
      findings of lower fear of success consequences among older adolescents than among
      younger ones, and the absence of significant sex difference among mid
      adolescents, were contrary to Horner's prediction. Possible explanations for
      these findings are considered. Suggestions for further research are mentioned. 

PMID- 24301043
TI  - Psychosocial factors associated with depression in urban adolescent females:
      Implications for assessment.
AB  - The major goals of this research were (1) to determine the incidence of
      depression in a nonclinical sample of urban adolescent females and (2) to
      identify demographic, sociocultural, and behavioral factors related to depression
      in this group. A racially and socioeconomically heterogeneous sample of 116
      adolescent girls was recruited from public high schools in the San Francisco Bay
      Area. Measures used were the Beck Depression Inventory, the Mooney Problem Check
      List, and a brief demographic questionnaire. Depression was found to be
      significantly related to parental occupation, geographical mobility, and number
      of self-reported problems. Implications for assessment are discussed. 

PMID- 24301044
TI  - The male experience of pubertal change.
AB  - Adolescent boys' psychological experience of the first ejaculation was examined
      with regard to emotional reactions to the event, feelings of preparedness prior
      to the event, informational sources, and extent of peer discussions following the
      event. Thirteen boys who ranged in age from 13 1/2 to 15 1/2 years were
      interviewed. Eleven of the boys had experienced an ejaculation; 55% felt they
      were well informed prior to the first ejaculation. However, only three had had
      ejaculation explained to them by another person, in all cases an adult male. The
      primary information source was reading material aquired from friends. The
      majority of the boys reported experiencing strong positive feelings at
      spermarche, and few had strong negative feelings. No one was upset or ashamed,
      and only two were very scared. The only boys who had discussed the experience
      were the three who received their initial information from adult males. No one
      had discussed the experience with peers. Differences and similarities in boys'
      experience of ejaculation and girls' experience of menarche are discussed. 

PMID- 24301045
TI  - Behavior problems of handicapped adolescent female students.

PMID- 24301046
TI  - Astrogliopathology: a central element of neuropsychiatric diseases?
AB  - Astroglia are the homoeostatic cells of the central nervous system that control a
      normal function of synaptically connected neuronal networks and contribute to
      brain defense. Recent advances in comprehension of pathological potential of
      astroglia indicate that astrocytes are fundamental for most (if not all)
      neurological diseases. Neuropathological and neuroimaging studies demonstrate
      prominent astroglial atrophy and astroglial asthenia occurring in most of
      neuropsychiatric illnesses. In chronic diseases such as schizophrenia and major
      depression, decrease in astroglial numbers and functional capabilities are,
      arguably, fundamental for pathological developments being responsible for
      neurotransmitter disbalance and failures in connectivity within neural networks.
      In neurodegenerative diseases atrophic changes in astrocytes are complemented by
      astrogliosis triggered by specific lesions such as senile plaques or dying
      neurons, these two processes contributing to cognitive decline and ultimately
      neuronal death. It is therefore possible to hypothesize that neuropsychiatric
      diseases represent a chronic astrogliopathology, which compromises glial
      homeostatic and defensive capabilities, and the degree and the alacrity of
      gliodegenerative changes define the progression and outcome of these disorders. 

PMID- 24301047
TI  - The globulin seed storage proteins of flowering plants are derived from two
      ancestral genes.
AB  - The cDNA and/or genomic DNA sequences of 13 globulin storage proteins from
      flowering plants (angiosperms) are now known. They represent 8 genera, 5 families
      and 5 orders of plants and include one monocotyledonous species. Here, the coding
      nucleotide and amino acid sequences of these proteins are compared by dot matrix
      analysis and gross protein domains visualized by hydropathy analyses. The
      vestigial homologies visualized by these means indicate that all of the globulin
      storage proteins of flowering plants have emanated from 2 genes that existed at
      the beginning of angiosperm evolution.A curious polypeptide domain of 150-200
      amino acids located near the N terminus is found in a globulin subgroup of 2
      genera widely separated phylogenetically. The domain appears to have resulted
      from an ancient insertion that has been deleted in most of its descendant genes. 

PMID- 24301048
TI  - Replication of the rRNA and legumin genes in synchronized root cells of pea
      (Pisum sativum): evidence for transient EcoR I sites in replicating rRNA genes.
AB  - The temporal pattern of replication of the rRNA and legumin genes differs in
      synchronized pea root cells. The relative number of rRNA genes replicated hourly
      during the first five hours of S phase ranges between 5 and 10 percent. In late S
      phase, during hours six through nine, the number of rRNA genes replicated
      increases reaching a maximum of about 25 percent at the ninth hour. Unlike the
      rRNA genes, the legumin genes have a wave-like pattern of replication peaking in
      early S phase at the third hour and again in late S phase at the eighth
      hour.Replicating rDNA, isolated by benzoylated naphthoylated DEAE-column
      chromatography, has EcoR I restriction sites that are absent in non-replicating
      rDNA sequences. The cleavage of these sites is independent of the time of rDNA
      replication. The transient nature of the EcoR I sites suggests that they exist in
      a hemimethylated state in parental DNA.The two Hind III repeat-size classes of
      rDNA of var. Alaska peas are replicated simultaneously as cells progress through
      S phase. Thus, even if the 9.0 kb and 8.6 kb repeat classes are located on
      different chromosomes, their temporal order of replication is the same. 

PMID- 24301049
TI  - TMV protein synthesis is not translationally regulated by heat shock.
AB  - Tobacco mosaic virus (TMV) protein synthesis in tobacco leaf tissue was not
      translationally regulated under conditions of heat shock as were most of the
      other proteins that were produced at 25 degrees C. Upon shift from 25 degrees C
      to 37-40 degrees C, most host protein synthesis was inhibited followed by
      initiation of synthesis of heat shock proteins. In contrast, TMV protein
      synthesis continued after the temperature shift. This phenomenon allowed the
      enhancement of detection of TMV protein synthesis in tobacco leaves. The most
      prominent proteins labeled were viral when tissue was labeled during the first hr
      following the shift to 40 degrees C, a period after heat shock repression of host
      protein synthesis, but before the onset of most heat shock protein synthesis.
      Another method to predominately label viral proteins was to incubate infected
      leaves for periods at 35 degrees C which induced repression of preexisting host
      protein synthesis without inducing synthesis of heat shock proteins. 

PMID- 24301050
TI  - Chloroplast genes encoding subunits of the H(+)-ATPase complex of Chlamydomonas
      reinhardtii are rearranged compared to higher plants: sequence of the atpE gene
      and location of the atpF and atpI genes.
AB  - The chloroplast gene for the epsilon subunit (atpE) of the CF1/CF0 ATPase in the
      green alga Chlamydomonas reinhardtii has been localized and sequenced. In
      contrast to higher plants, the atpE gene does not lie at the 3' end of the beta
      subunit (atpB) gene in the chloroplast genome of C. reinhardtii, but is located
      at a position 92 kb away in the other single copy region. The uninterrupted open
      reading frame for the atpE gene is 423 bp, and the epsilon subunit exhibits 43%
      derived amino acid homology to that from spinach. Codon usage for the atpE gene
      follows the restricted pattern seen in other C. reinhardtii chloroplast genes.The
      genes for the CF0 subunits I (atpF) and IV (atpI) of the ATPase complex have also
      been mapped on the chloroplast genome of C. reinhardtii. The six chloroplast
      ATPase genes in C. reinhardtii are dispersed individually between the two single
      copy regions of the chloroplast genome, an organization strikingly different from
      the highly conserved arrangement in two operon-like units seen in chloroplast
      genomes of higher plants. 

PMID- 24301051
TI  - Chromatin structure of integrated T-DNA in crown gall tumors.
AB  - We have investigated the chromatin structure of the integrated T-DNA in two N.
      tabacum crown gall tumor lines, and compared the results to those obtained in a
      previous study of the methylation patterns of these same integrated DNA sequences
      (Gelvin et al., Nucleic Acids Res. 11:159-174, 1983). The E9 octopine-type tumor
      contains a single copy of TL, whose transcription is essential for tumor
      maintenance, and 15-30 copies of TR, a non-essential region. The HT37#15 nopaline
      type teratoma contains a single copy of the nopaline T-DNA. All these integrated
      sequences can be found associated with nucleosomes, although the diffuse nature
      of the nucleosome bands on Southern transfers implies an 'open' chromatin
      conformation. In addition, all the sequences are more sensitive to digestion with
      deoxyribonuclease I than the bulk of the chromatin. We present evidence
      suggesting that, despite the previously published data that the majority of
      copies of the TR-DNA are highly methylated at the sequence CCGG whereas the TL
      DNA is not, the majority of copies of the TR-DNA in the E9 tumor line are in the
      same chromatin conformation as TL. These data therefore suggest that most of the
      copies of TR-DNA are likely to be transcriptionally competent. 

PMID- 24301052
TI  - Relations between the plastid gene dosage and the levels of 16S rRNA and rbcL
      gene transcripts during amyloplast to chloroplast change in mixotrophic spinach
      cell suspensions.
AB  - Spinach cell suspension cultures maintained in photomixotrophic conditions
      exhibit plastids which undergo cyclic morphological transformations along a
      growth cycle. Ultrastructural studies show that the green chloroplasts present at
      the initial stage differentiate into amyloplasts during the subsequent log phase
      and then return to chloroplasts in stationary phase. The changes of the levels of
      plastid DNA (pt DNA) per cell have been determined along the growth cycle, as a
      percentage of total DNA by hybridization of definite amounts of total DNA to a
      radioactive probe of cloned pt DNA. The number of pt DNA copies have been
      estimated to 1125 per cell at the maximum of amyloplast development and to 5940
      copies per cell at the maximum of chloroplast differentiation. Hybridizations of
      defined amounts of total cellular RNA to labelled probes of the 16S rDNA and of
      the rbcL gene allowed estimations of the variations of the corresponding cellular
      RNA pools. These variations are well correlated with the changes of the ptDNA
      cellular levels. These results show that the ptDNA gene dosage plays a central
      role in the regulation of the plastid transcript levels in this system. 

PMID- 24301053
TI  - Genomic organization and nucleotide sequences of two histone H3 and two histone
      H4 genes of Arabidopsis thaliana.
AB  - Two histone H3 and two histone H4 genes have been cloned from a
      lambdagtWESlambda.B Arabidopsis thaliana gene library. From their nucleotide
      sequences and from studies on their genomic organization, the following
      conclusions can be drawn: : 1) The nucleotide sequences of the two H3 coding
      regions show only 85% homology, but encode the same proteins. The Arabidopsis H3
      has the same amino acid sequence as its counterpart in corn, but differs from
      that of pea and wheat by replacement in position 90 of a serine by an alanine.
      The two H4 coding regions have 97% sequence homology and encode the same protein,
      identical to the sequence of their counterpart in pea, corn and one H4 variant in
      wheat. 2) The 5'-flanking regions of the 4 genes contain the classical histone
      gene-specific consensus sequences, except H3A725 which lacks the GATCC-like
      pentamer. The conserved octanucleotide 5'-CGCGGATC-3' which was previously found
      in the 5'-flanking sequences of corn and wheat H3 and H4 genes is also present in
      all four genes described here approximately 200 to 250 nucleotides upstream from
      the initiation ATG. The 5'-flanking regions of the H4 genes display extensive
      sequence homology, whereas those of the H3 genes do not. 3) The 3'-flanking
      regions do not possess the classical histone-gene-specific T hyphenated dyad
      symmetry motif. 4) Each H3 and H4 gene exists as 5 to 7 copies per haploid
      genome. 

PMID- 24301054
TI  - Erratum.

PMID- 24301055
TI  - Production of apolipoprotein C-III knockout rabbits using zinc finger nucleases.
AB  - Apolipoprotein (Apo) C-III (ApoCIII) resides on the surface of plasma chylomicron
      (CM), very low density lipoprotein (VLDL) and high density lipoproteins (HDL). It
      has been recognized that high levels of plasma ApoCIII constitutea risk factor
      for cardiovascular diseases (CVD). Elevated plasma ApoCIII level often correlates
      with insulin resistance, obesity, and hypertriglyceridemia. Invaluable knowledge
      on the roles of ApoCIIIin lipid metabolisms and CVD has been obtained from
      transgenic mouse models including ApoCIII knockout (KO) mice; however, it is
      noted that the metabolism of lipoprotein in mice is different from that of humans
      in many aspects. It is not known until now whether elevated plasma ApoCIII is
      directly atherogenic. We worked to develop ApoCIII KO rabbits in the present
      study based on the hypothesis that rabbits can serve as a reasonablemodelfor
      studying human lipid metabolism and atherosclerosis. Zinc finger nuclease (ZFN)
      sets targeting rabbit ApoCIIIgene were subjected to in vitro validation prior to
      embryo microinjection. The mRNA was injected to the cytoplasm of 35 rabbit
      pronuclear stage embryos, and evaluated the mutation rates at the blastocyst
      state. Of sixteen blastocysts that were assayed, a satisfactory 50% mutation rate
      (8/16) at the targeting site was achieved, supporting the use of Set 1 for in
      vivo experiments. Next, we microinjected 145 embryos with Set 1 mRNA, and
      transferred these embryos to 7 recipient rabbits. After 30 days gestation, 21
      kits were born, out of which five were confirmed as ApoCIII KO rabbits after PCR
      sequencing assays. The KO animal rate (#KO kits/total born) was 23.8%. The
      overall production efficiency is 3.4% (5 kits/145 embryos transferred). The
      present work demonstrated that ZFN is a highly efficient method to produce KO
      rabbits. These ApoCIII KO rabbits are novel resources to study the roles of
      ApoCIII in lipid metabolisms. 

PMID- 24301056
TI  - Further delineation of the SATB2 phenotype.
AB  - SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on
      chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial
      role in craniofacial patterning and osteoblast differentiation, as well as in
      determining the fates of neuronal projections in the developing neocortex. In
      humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2
      haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and
      intellectual disability (ID). A single patient carrying a nonsense mutation in
      SATB2 has been described to date. In this study, we performed trio-exome
      sequencing in a 3-year-old girl with CP and severely delayed speech development,
      and her unaffected parents. Previously, the girl had undergone conventional and
      molecular karyotyping (microarray analysis), as well as targeted analysis for
      different diseases associated with developmental delay, including Angelman
      syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be
      established. Exome sequencing revealed a de novo nonsense mutation in the SATB2
      gene (c.715C>T; p.R239*). The identification of a second patient carrying a de
      novo nonsense mutation in SATB2 confirms that this gene is essential for normal
      craniofacial patterning and cognitive development. Based on our data and the
      literature published so far, we propose a new clinically recognizable syndrome -
      the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and
      should be considered in children with ID, severe speech delay, cleft or high
      arched palate and abnormal dentition with crowded and irregularly shaped teeth. 

PMID- 24301057
TI  - Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic
      diseases: a collaborative ESHRE PGD consortium study.
AB  - Preimplantation genetic diagnosis (PGD) for monogenic disorders currently
      involves polymerase chain reaction (PCR)-based methods, which must be robust,
      sensitive and highly accurate, precluding misdiagnosis. Twelve adverse
      misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate.
      This retrospective study, involving six PGD centres, assessed the validity of PCR
      based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles.
      Data were collected on the genotype concordance at PGD and follow-up from 940
      untransferred embryos, including details on the parameters of PGD cycles:
      category of monogenic disease, embryo morphology, embryo biopsy and genotype
      assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se),
      specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses
      were also conducted to assess the influence of the parameters above on the
      validity of PCR-based PGD. The analysis of overall data showed that 93.7% of
      embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp
      of 80.9%. The stratified analyses found that diagnostic accuracy is statistically
      significantly higher when PGD is performed on two cells versus one cell
      (P=0.001). Se was significantly higher when multiplex protocols versus singleplex
      protocols were applied (P=0.005), as well as for PGD applied on cells from good
      compared with poor morphology embryos (P=0.032). Morphology, however, did not
      affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as
      robust as those on two cells regarding false negative rate, which is the most
      important criteria for clinical PGD applications. Overall, this study
      demonstrates the validity, robustness and high diagnostic value of PCR-based PGD.

PMID- 24301059
TI  - VHL mosaicism can be detected by clinical next-generation sequencing and is not
      restricted to patients with a mild phenotype.
AB  - The identification of Von Hippel-Lindau (VHL) mosaic mutations by conventional
      Sanger sequencing requires a labour-intensive enrichment step, thus explaining
      that mosaicism occurrence is underestimated in patients. Nowadays, it is possible
      to detect mutation in cell sub-populations by next-generation sequencing (NGS).
      Here, we described a diagnosis strategy using NGS with high coverage in a series
      of eight patients who were negative for a VHL abnormality by Sanger sequencing
      and deletion search. In two patients, a mosaic mutation in VHL was detected by
      NGS. One patient with a 5.7% mutated allele frequency had a severe phenotype and
      an early disease onset. In conclusion, clinical NGS in an hospital molecular
      oncogenetics laboratory is an efficient tool to identify VHL mosaic mutation. Its
      use may improve patient monitoring and genetic counseling. 

PMID- 24301058
TI  - Replication of the effect of SLC2A9 genetic variation on serum uric acid levels
      in American Indians.
AB  - Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal
      and cardiovascular diseases, is caused by either increased production or
      decreased excretion of uric acid or a mix of both. The solute carrier protein 2
      family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux
      across the renal proximal tubule. Genome-wide association studies have
      consistently shown the association of single-nucleotide polymorphisms in this
      gene with SUA in majority populations. American Indian participants of the Strong
      Heart Family Study, belonging to multigenerational families, have high prevalence
      of hyperuricemia. We conducted measured genotype analyses, based on variance
      components decomposition method and accounting for family relationships, to
      assess whether the association between SUA and SLC2A9 gene polymorphisms
      generalized to American Indians (n=3604) of this study. Seven polymorphisms were
      selected for genotyping based on their association with SUA levels in other
      populations. A strong association was found between SLC2A9 gene polymorphisms and
      SUA in all centers combined (P-values: 1.3 * 10(-31)-5.1 * 10(-23)) and also when
      stratified by recruitment center; P-values: 1.2 * 10(-14)-1.0 * 10(-5). These
      polymorphisms were also associated with the estimated glomerular filtration rate
      and serum creatinine but not albumin-creatinine ratio. In summary, the
      association of polymorphisms in the uric acid transporter gene with SUA levels
      extends to a new population of American Indians. 

PMID- 24301061
TI  - GWAS Central: a comprehensive resource for the comparison and interrogation of
      genome-wide association studies.
AB  - To facilitate broad and convenient integrative visualization of and access to
      GWAS data, we have created the GWAS Central resource
      (http://www.gwascentral.org). This database seeks to provide a comprehensive
      collection of summary-level genetic association data, structured both for maximal
      utility and for safe open access (i.e., non-directional signals to fully preclude
      research subject identification). The resource emphasizes on advanced tools that
      allow comparison and discovery of relevant data sets from the perspective of
      genes, genome regions, phenotypes or traits. Tested markers and relevant genomic
      features can be visually interrogated across up to 16 multiple association data
      sets in a single view, starting at a chromosome-wide view and increasing in
      resolution down to individual bases. In addition, users can privately upload and
      view their own data as temporary files. Search and display utility is further
      enhanced by exploiting phenotype ontology annotations to allow genetic variants
      associated with phenotypes and traits of interest to be precisely identified,
      across all studies. Data submissions are accepted from individual researchers,
      groups and consortia, whereas we also actively gather data sets from various
      public sources. As a result, the resource now provides over 67 million P-values
      for over 1600 studies, making it the world's largest openly accessible online
      collection of summary-level GWAS association information. 

PMID- 24301060
TI  - Development of primary early-onset colorectal cancers due to biallelic mutations
      of the FANCD1/BRCA2 gene.
AB  - Fanconi anaemia (FA) is characterized by progressive bone marrow failure,
      congenital anomalies, and predisposition to malignancy. In a minority of cases,
      FA results from biallelic FANCD1/BRCA2 mutations that are associated with early
      onset leukaemia and solid tumours. Here, we describe the clinical and molecular
      features of a remarkable family presenting with multiple primary colorectal
      cancers (CRCs) without detectable mutations in genes involved in the Mendelian
      predisposition to CRCs. We unexpectedly identified, despite the absence of
      clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2
      corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and
      a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed
      by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR
      analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing
      mutation that creates an aberrant splicing donor site and results partly into an
      aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The
      atypical FA phenotype observed within this family was probably explained by the
      residual amount of BRCA2 with the point mutation c.7802A>G in the patients
      harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in
      a single family, it suggests that CRCs may be part of the tumour spectrum
      associated with FANCD1/BRCA2 biallelic mutations and that the presence of such
      mutations should be considered in families with CRCs, even in the absence of
      cardinal features of FA. 

PMID- 24301062
TI  - Diversity and complexity in the pyramidal tract projectome.

PMID- 24301065
TI  - Corticostriatal and mesocortical dopamine systems: do species differences matter?

PMID- 24301066
TI  - Behavioural neuroscience: the feminine touch dampens aggression.

PMID- 24301067
TI  - Neural repair: export duties for HDAC5.

PMID- 24301068
TI  - Sensory systems: connecting olfaction.

PMID- 24301071
TI  - Automatic treatment plan re-optimization for adaptive radiotherapy guided with
      the initial plan DVHs.
AB  - Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve
      tumor control through treatment adaptations based on the current patient anatomy.
      Developing an efficient and effective re-planning algorithm is an important step
      toward the clinical realization of ART. For the re-planning process, manual trial
      and-error approach to fine-tune planning parameters is time-consuming and is
      usually considered unpractical, especially for online ART. It is desirable to
      automate this step to yield a plan of acceptable quality with minimal
      interventions. In ART, prior information in the original plan is available, such
      as dose-volume histogram (DVH), which can be employed to facilitate the automatic
      re-planning process. The goal of this work is to develop an automatic re-planning
      algorithm to generate a plan with similar, or possibly better, DVH curves
      compared with the clinically delivered original plan. Specifically, our algorithm
      iterates the following two loops. An inner loop is the traditional fluence map
      optimization, in which we optimize a quadratic objective function penalizing the
      deviation of the dose received by each voxel from its prescribed or threshold
      dose with a set of fixed voxel weighting factors. In outer loop, the voxel
      weighting factors in the objective function are adjusted according to the
      deviation of the current DVH curves from those in the original plan. The process
      is repeated until the DVH curves are acceptable or maximum iteration step is
      reached. The whole algorithm is implemented on GPU for high efficiency. The
      feasibility of our algorithm has been demonstrated with three head-and-neck
      cancer IMRT cases, each having an initial planning CT scan and another treatment
      CT scan acquired in the middle of treatment course. Compared with the DVH curves
      in the original plan, the DVH curves in the resulting plan using our algorithm
      with 30 iterations are better for almost all structures. The re-optimization
      process takes about 30 s using our in-house optimization engine. 

PMID- 24301072
TI  - Biomimetic strategies incorporating enzymes into CaP coatings mimicking the in
      vivo environment.
AB  - Biomimetic calcium phosphate coating (CaP) methodology mimics the natural
      biomineralization process of bone, which involves two phases: nucleation and
      growth. In this chapter we present a successful method to coating biodegradable
      natural-origin materials with biomimetic CaP layer as a strategy to incorporate
      enzymes with the main aim of controlling and tailoring their degradation over
      time. This strategy seems to enhance the bone-bonding, osteoconductive, and
      osteoinductive properties of natural-origin biomaterials that per se do not
      present these characteristics.

PMID- 24301073
TI  - Efficient Production of Photoreceptor Precursor Cells from Human Embryonic Stem
      Cells.
AB  - Transplantation of photoreceptor precursor cells (PPCs) differentiated from human
      embryonic stem cells (hESCs) is a promising approach to treat common blinding
      diseases such as age-related macular degeneration and retinitis pigmentosa.
      However, existing PPC generation methods are inefficient. To enhance
      differentiation protocols for rapid and high-yield production of PPCs, we focused
      on optimizing the handling of the cells by including feeder-independent growth of
      hESCs, using size-controlled embryoid bodies (EBs), and addition of
      triiodothyronine (T3) and taurine to the differentiation medium, with subsequent
      removal of undifferentiated cells via negative cell-selection. Our novel protocol
      produces higher yields of PPCs than previously reported while reducing the time
      required for differentiation, which will help understand retinal diseases and
      facilitate large-scale preclinical trials. 

PMID- 24301074
TI  - Dual-SMAD Inhibition/WNT Activation-Based Methods to Induce Neural Crest and
      Derivatives from Human Pluripotent Stem Cells.
AB  - The neural crest (NC) is a transient population of multipotent cells giving rise
      to the peripheral nervous system, skin pigmentation, heart, and facial
      mesenchyme. The broad cell fate potential of NC makes it an attractive cell fate
      to derive from human pluripotent stem cells (hPSCs) for exploring embryonic
      development, modeling disease, and generating cells for transplantation. Here, we
      discuss recent publications and methods for efficiently differentiating hPSCs
      into NC. We also provide methods to direct NC into two different terminal fates:
      melanocytes and sensory neurons. 

PMID- 24301075
TI  - Organoselenium(II) halides containing the pincer 2,6-(Me2NCH2)2C6H3 ligand--an
      experimental and theoretical investigation.
AB  - New organoselenium(II) halides of the type [RSe](+)X(-) [R = 2,6-(Me2NCH2)2C6H3;
      X = Cl (2), Br (3), I (4)] were prepared by cleavage of the Se-Se bond in R2Se2
      (1) with SO2Cl2 followed by halogen exchange when organoselenium chloride was
      treated with NaBr or KI. The reaction between 2 and R'2MCln resulted in new ionic
      [RSe](+)[R'2MCl(n+1)](-) [R' = 2-(Me2NCH2)C6H4, n = 1, M = Sb (5), Bi (6); R' =
      Ph, M = Sb, n = 1 (7) or n = 3 (8)] species. All new compounds were investigated
      in solution by multinuclear NMR spectroscopy ((1)H, (13)C, (77)Se, 2D
      experiments) and mass spectrometry. The ionic nature of 2 and the antimonates
      species was confirmed by conductivity studies. The molecular structures of [{2,6
      (Me2NCH2)2C6H3}Se](+)Cl(-).nH2O (2.H2O and 2.2H2O) and [{2,6
      (Me2NCH2)2C6H3}Se](+)[Ph2SbCl4](-) (8), respectively, were established by single
      crystal X-ray diffraction, pointing out that the ionic nature of these compounds
      is also preserved in the solid state, with both nitrogen atoms strongly trans
      coordinated to the selenium atom of the cation. Theoretical calculations carried
      out at the DFT level were exploited to investigate the nature of the bonding in
      compounds 2-4 and the free cation [RSe](+) (2a). A topological analysis based on
      the theory of Atoms-In-Molecules (AIM) and Electron Localization Function (ELF)
      jointly to a Natural Bond Orbital (NBO) approach was used to shed light on the
      effect of the nature of the halogen species X on the bonding within the 3c-4e N
      Se-N moiety.

PMID- 24301076
TI  - Programmed hydrolysis of nanoassemblies by electrostatic interaction-mediated
      enzymatic-degradation.
AB  - Electrostatic interaction-mediated enzymatic-hydrolysis of poly(lactide)
      containing nanoscale assemblies is described. At physiological pH, degradable
      core-shell morphologies with charged shells can readily attract or repel enzymes
      carrying opposite or similar charges, respectively. 

PMID- 24301077
TI  - Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.
AB  - Literature and experimental data relevant to the decision to allow a waiver of in
      vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid
      oral dosage forms containing piroxicam in the free acid form are reviewed.
      Piroxicam solubility and permeability, its therapeutic use and therapeutic index,
      pharmacokinetic properties, data related to the possibility of excipient
      interactions and reported BE/bioavailability (BA), and corresponding dissolution
      data are taken into consideration. The available data suggest that according to
      the current biopharmaceutics classification system (BCS) and all current
      guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam
      absorption seems not to depend on manufacturing conditions or excipients, so the
      risk of bioinequivalence in terms of area under the curve (AUC) is very low, but
      the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the
      formulation. Current in vitro dissolution methods may not always reflect
      differences in terms of Cmax for BCS Class II weak acids; however, minor
      differences in absorption rate of piroxicam would not subject the patient to
      unacceptable risks: as piroxicam products may be taken before or after meals, the
      rate of absorption cannot be considered crucial to drug action. Therefore, a
      biowaiver for IR piroxicam solid oral dosage form is considered feasible,
      provided that (a) the test product contains only excipients, which are also
      present in IR solid oral drug products containing piroxicam, which have been
      approved in ICH or associated countries, for instance, those presented in Table 3
      of this paper; (b) both the test and comparator drug products dissolve 85% in 30
      min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show
      dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these
      conditions can be fulfilled, BE of the products should be established in vivo.

PMID- 24301078
TI  - The femur of Orrorin tugenensis exhibits morphometric affinities with both
      Miocene apes and later hominins.
AB  - Orrorin tugenensis (Kenya, ca. 6 Ma) is one of the earliest putative hominins.
      Its proximal femur, BAR 1002'00, was originally described as being very human
      like, although later multivariate analyses showed an australopith pattern.
      However, some of its traits (for example, laterally protruding greater
      trochanter, medially oriented lesser trochanter and presence of third trochanter)
      are also present in earlier Miocene apes. Here, we use geometric morphometrics to
      reassess the morphological affinities of BAR 1002'00 within a large sample of
      anthropoids (including fossil apes and hominins) and reconstruct hominoid
      proximal femur evolution using squared-change parsimony. Our results indicate
      that both hominin and modern great ape femora evolved in different directions
      from a primitive morphology represented by some fossil apes. Orrorin appears
      intermediate between Miocene apes and australopiths in shape space. This evidence
      is consistent with femoral shape similarities in extant great apes being derived
      and homoplastic and has profound implications for understanding the origins of
      human bipedalism.

PMID- 24301080
TI  - Population divergence in the wheat leaf rust fungus Puccinia triticina is
      correlated with wheat evolution.
AB  - Co-evolution of fungal pathogens with their host species during the domestication
      of modern crop varieties has likely affected the current genetic divergence of
      pathogen populations. The objective of this study was to determine if the
      evolutionary history of the obligate rust pathogen on wheat, Puccinia triticina,
      is correlated with adaptation to hosts with different ploidy levels. Sequence
      data from 15 loci with different levels of polymorphism were generated.
      Phylogenetic analyses (parsimony, Bayesian, maximum likelihood) showed the clear
      initial divergence of P. triticina isolates collected from Aegilops speltoides
      (the likely B genome donor of modern wheat) in Israel from the other isolates
      that were collected from tetraploid (AB genomes) durum wheat and hexaploid (ABD
      genomes) common wheat. Coalescence-based genealogy samplers also indicated that
      P. triticina on A. speltoides, diverged initially, followed by P. triticina
      isolates from durum wheat in Ethiopia and then by isolates from common wheat.
      Isolates of P. triticina found worldwide on cultivated durum wheat were the most
      recently coalesced and formed a clade nested within the isolates from common
      wheat. By a relative time scale, the divergence of P. triticinia as delimited by
      host specificity appears very recent. Significant reciprocal gene flow between
      isolates from common wheat and isolates from durum wheat that are found worldwide
      was detected, in addition to gene flow from isolates on common wheat to isolates
      on durum wheat in Ethiopia. 

PMID- 24301081
TI  - Improving end-of-life care in hospitals: a qualitative analysis of bereaved
      families' experiences and suggestions.
AB  - OBJECTIVES: To explore and document the experiences and expectancies of bereaved
      family members concerning the end-of-life (EOL) care of their deceased relative
      in a general hospital setting. METHODS: Cross-sectional study using a
      questionnaire that included open-ended questions. Free-text answers were
      evaluated with qualitative content analysis. A total of 270 family members
      provided information about improvements in inpatient care. RESULTS: Families
      described structural deficiencies. Furthermore, they requested a more holistic
      patient health care beyond medical treatment and expressed the wish for more
      professional support for families. DISCUSSION: The view of bereaved families
      confirmed the need for improvement in general hospital EOL care. The results
      underline the importance of a more holistic EOL care. The application of
      communication skills training, structured family meetings, and integrated
      pathways is recommended.

PMID- 24301082
TI  - Palliative care consultation versus palliative care unit: which is associated
      with shorter terminal hospitalization length of stay among patients with cancer?
AB  - Hospital length of stay (LoS) may be used to assess end-of-life care
      aggressiveness and health care delivery efficiency. We describe the terminal
      hospitalization LoS of patients with cancer managed by a hospital-based
      palliative care (PC) program comprising a palliative care consultation (PCC)
      service and an inpatient palliative care unit (PCU). A total of 328 in-hospital
      cancer deaths were divided into 2 groups. The PCU group included patients
      admitted by the PC team directly to the PCU. The PCC group included patients
      admitted by other specialties and referred to the PCC team. The LoS of the PCU
      group was significantly shorter than that of the PCC group (9.9 [+/-9.4] vs 17.8
      [+/-19.7] days, respectively; P < .001). Direct terminal hospitalization to PCU
      is not associated with longer LoS among cancer deaths managed by a hospital-based
      PC service.

PMID- 24301083
TI  - The benefits of rehabilitation for palliative care patients.
AB  - Palliative care requires an interdisciplinary team approach to provide the best
      care for patients with life-threatening illnesses. Like palliative medicine,
      rehabilitation also uses an interdisciplinary approach to treating patients with
      chronic illnesses. This review article focuses on rehabilitation interventions
      that can be beneficial in patients with late stage illnesses. Rehabilitation may
      be useful in improving the quality of life by palliating function, mobility,
      activities of daily living, pain relief, endurance, and the psyche of a patient
      while helping to maintain as much independence as possible, leading to a decrease
      in burden on caregivers and family. Rehabilitative services are underutilized in
      the palliative care setting, and more research is needed to address how patients
      may benefit as they approach the end of their lives. 

PMID- 24301084
TI  - Difficulties in caring for a patient with cancer at the end of life at home and
      complicated grief.
AB  - The present study aimed to investigate difficulties in caring for a patient with
      cancer at the end of life at home and to examine relationships between
      difficulties with care and complicated grief. The 45 bereaved family members
      completed the Family Difficulty Scale (FDS) and the Inventory of Complicated
      Grief (ICG). The FDS score for "Patient's pain and condition" was the highest,
      followed by "Caregivers did not want home care" and "No support from others."
      There was a significant relationship between FDS and ICG scores. These results
      suggest that the condition of the patient, the view of the caregiver on home
      care, and the absence of other support are important factors contributing to
      difficulties of family caregivers, and that these difficulties may lead to
      complicated grief. 

PMID- 24301085
TI  - A favorable course of palliative sedation: searching for indicators using
      caregivers' perspectives.
AB  - OBJECTIVE: Comparing characteristics of a favorable sedation course during
      palliative sedation to a less favorable course based on the reports Dutch
      physicians and nurses. RESULTS: Cases identified as having a favorable sedation
      course less often concerned a male patient (P = .019 nurses' cases), reached the
      intended sedation depth significantly quicker (P < .05 both nurses and
      physicians' cases), reached a deeper level of sedation (P = .015 physicians'
      cases), and had a shorter total duration of sedation compared (P < .001
      physicians' cases) to patients with a less favorable sedation course.
      CONCLUSIONS: A favorable course during palliative sedation seems more probable
      when health care professionals report on a (relatively) shorter time to reach the
      required depth of sedation and when a deeper level of sedation can be obtained.

PMID- 24301086
TI  - Prediction of the location and size of the stomach using patient characteristics
      for retrospective radiation dose estimation following radiotherapy.
AB  - Following cancer radiotherapy, reconstruction of doses to organs, other than the
      target organ, is of interest for retrospective health risk studies. Reliable
      estimation of doses to organs that may be partially within or fully outside the
      treatment field requires reliable knowledge of the location and size of the
      organs, e.g., the stomach, which is at risk from abdominal irradiation. The
      stomach location and size are known to be highly variable between individuals,
      but have been little studied. Moreover, for treatments conducted years ago,
      medical images of patients are usually not available in medical records to locate
      the stomach. In light of the poor information available to locate the stomach in
      historical dose reconstructions, the purpose of this work was to investigate the
      variability of stomach location and size among adult male patients and to develop
      prediction models for the stomach location and size using predictor variables
      generally available in medical records of radiotherapy patients treated in the
      past. To collect data on stomach size and position, we segmented the contours of
      the stomach and of the skeleton on contemporary computed tomography (CT) images
      for 30 male patients in supine position. The location and size of the stomach was
      found to depend on body mass index (BMI), ponderal index (PI), and age. For
      example, the anteroposterior dimension of the stomach was found to increase with
      increasing BMI (~0.25 cm kg(-1) m(2)) whereas its craniocaudal dimension
      decreased with increasing PI (~-3.3 cm kg(-1) m(3)) and its transverse dimension
      increased with increasing PI (~2.5 cm kg(-1) m(3)). Using the prediction models,
      we generated three-dimensional computational stomach models from a deformable
      hybrid phantom for three patients of different BMI. Based on a typical
      radiotherapy treatment, we simulated radiotherapy treatments on the predicted
      stomach models and on the CT images of the corresponding patients. Those dose
      calculations demonstrated good agreement between predicted and actual stomachs
      compared with doses derived from a reference model of the body that might be used
      in the absence of individual CT scan data.

PMID- 24301088
TI  - Molecular epidemiology of human respiratory syncytial virus over three
      consecutive seasons in Latvia.
AB  - Lower respiratory tract infections caused by the human respiratory syncytial
      virus (HRSV) represent an immense burden of the disease, especially in young
      children. This study aimed to investigate the evolutionary history of HRSV
      strains isolated in the Children's Clinical University Hospital (Riga, Latvia)
      over three consecutive HRSV seasons. Of 207 samples from children hospitalized
      with lower respiratory tract infections, 88 (42.5%) tested positive for HRSV by
      RT-PCR. The seasonal activity started and peaked later than the average for the
      Northern hemisphere. Patients with HRSV lower respiratory tract infection were
      significantly younger than patients not infected with HRSV. HRSV-A viruses
      predominated for two consecutive seasons and were followed by an HRSV-B dominant
      season. Phylogenetic analysis based on glycoprotein G gene partial sequences
      revealed that viruses of both groups belonged to the worldwide dominant genotypes
      NA1 (HRSV-A) and BA-IV (HRSV-B). High diversity of this gene was driven only
      partially by selection pressure, as only two positively selected sites were
      identified in each group. Two of the HRSV-A isolates in this study contained a 72
      nt duplication in the C-terminal end of the G gene (genotype ON1) that was first
      described in Canada in the 2010-2011 season. Initial spatial and temporal
      dynamics of this novel genotype were reconstructed by discrete phylogeographic
      analysis. Fifteen years after acquiring comparable 60-nt duplication in the G
      gene, genotype BA lineages have replaced all other HRSV-B strains. However, the
      population size of genotype ON1 plateaued soon and even decreased slightly before
      the beginning of the 2012-2013 season.

PMID- 24301089
TI  - Proteomic analysis of perfluorooctane sulfonate-induced apoptosis in human
      hepatic cells using the iTRAQ technique.
AB  - Perfluorooctane sulfonate (PFOS) is one of the most commonly used perfluorinated
      compounds, whose environmental exposure has been associated with a number of
      adverse health outcomes. However, the molecular mechanisms involved in PFOS
      toxicity are still not well elucidated. In the present study, we applied iTRAQ
      labeling quantitative proteomic technology to investigate the differential
      protein expression profiles of non-tumor human hepatic cells (L-02) exposed to
      PFOS. A total of 18 proteins were differentially expressed in a dose-dependent
      manner in PFOS-treated cells versus the control. Among these, 11 proteins were up
      regulated and 7 were down-regulated. Gene ontology analysis indicated that PFOS
      would exert toxic effects on L-02 cells by affecting multiple biological
      processes, including protein biosynthesis and degradation, mRNA processing and
      splicing, transcription, signal transduction and transport. Furthermore, the
      proteomic results especially proposed that the inhibition of HNRNPC, HUWE1 and
      UBQLN1, as well as the induction of PAF1 is involved in the activation of the p53
      and c-myc signaling pathways, which then trigger the apoptotic process in L-02
      cells exposed to PFOS. Overall, these data will aid our understanding of the
      mechanisms responsible for PFOS-mediated hepatotoxicity, and develop useful
      biomarkers for monitoring and evaluating PFOS contamination in the environment.

PMID- 24301091
TI  - Gold(I) complexes with heteroaryl phosphine ligands.
AB  - Gold(I) complexes ligated by phosphines with N-heterocycles in the periphery were
      prepared. First the synthesis of the ligands N-(diphenylphosphino)-4-(pyridin-2
      yl)pyrimidin-2-amine (Hpypya) and N-(diphenylphosphino)-4-phenylpyrimidin-2-amine
      (Hphpya) are reported. These two compounds together with the related but earlier
      published ligands 3-(2-(diphenylphosphino)phenyl)-1H-pyrazole (Hph3py) and 5-(4
      (diphenylphosphino)phenyl)-1H-pyrazole (Hph5py) were reacted with [(tht)AuCl] and
      [Au(tht)2]ClO4 to give the heteroleptic complexes [(L)AuCl] and the homoleptic
      compounds [(L)2Au]ClO4 (L = Hpypya, Hphpya, Hph3py, and Hph5py). Single crystal X
      ray diffraction studies revealed that the heteroleptic complexes form hydrogen
      bonds between two N-heterocycles of neighboring complexes resulting in dimeric
      structures. The homoleptic complexes show a different behavior.

PMID- 24301090
TI  - Computed tomography scans as an objective measure of disease severity in chronic
      rhinosinusitis.
AB  - OBJECTIVES: A truly objective method of measuring disease severity in chronic
      rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography
      (CT) scans of CRS patients using this novel objective 3D computerized system and
      compared results with a novel 2D computerized analysis of a single coronal slice
      through the osteomeatal complex (OMC) and subjective methods including Lund
      Mackay and Zinreich's modified Lund-Mackay. STUDY DESIGN: Prospective multicenter
      study. SETTING: Two academic tertiary referral centers. SUBJECTS AND METHODS:
      Forty-six adults with a diagnosis of CRS underwent CT examination and received an
      intramuscular triamcinolone injection, dosage weight dependent, followed by CT
      scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with
      all 4 scoring methods over 5 months. RESULTS: The Lin's concordance class
      correlation (CCC) of the OMC method revealed the best correlation to the 3D
      volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund
      Mackay methods (0.824). Posttreatment results demonstrated that both the OMC
      (0.824) and Zinreich's (0.778) methods had strong agreement with the 3D
      volumetric methods and were very sensitive to change, whereas the Lund-Mackay
      (0.545) had only moderate agreement. CONCLUSION: Computerized CT analysis
      provides the most comprehensive, objective, and reproducible method of measuring
      disease severity and is very sensitive to change induced by treatment
      intervention. A 2D coronal image through the OMC provides a valid, user-friendly
      method of assessing CRS and is representative of CRS severity in all sinuses.
      Zinreich's subjective method correlated well overall, but the Lund-Mackay method
      lagged behind in disease representation and sensitivity to change.

PMID- 24301092
TI  - Cytoplasmic male sterility in barley : Part 7: nuclear genes for restoration.
AB  - Restoration in the msm1 cytoplasm of barley (Hordeum vulgare L. s.l.) was studied
      from the standpoint of population biology and physiological effects on kernel
      protein. Restorer genes of 82 accessions of wild barley (ssp. spontaneum) from
      Israel were determined. 38% of the accessions were maintainers of sterility, 48%
      were partial restorers, and 14% were restorers. Fourteen dominant restorer genes
      are described, and evidence for three cases of allelism to Rfm1a is presented.
      The restorer accessions and their designated gene symbols are: PI 282636
      (Rfm,,e), PI 282637 (Rfm,f), PI 282646 (Rfm,,g), PI 284742 (Rfm,h), PI 284743
      (Rfm,,i), PI 284753 (Rfm,,j), PI 284755 (Rfm1d), PI 296838 (Rfm,,k), PI 296850
      isolate 16/7 (Rfm,,l), PI 296853 (Rfm,,m), PI 296856 (Rfm1b), PI 296899 (Rfm,,n),
      PI 296919 (Rfm1c), PI 296944 (Rfm,,o). PI 296850 was found to contain both a
      restorer and a non-restorer genotype. None of the PI accessions with a restorer
      gene is a carrier of an msm1-type male sterilizing cytoplasm. In the present
      sample, plants with restoration ability occurred with a higher frequency in the
      material from the Judean Foothills than that from the other regions of Israel.
      The greater adaptive value of plants with restoration ability on certain soil
      associations in semiarid and subhumic climate is suggested. The considerable
      frequency of restorers and partial restorers in male fertile cytoplasm suggests
      that the restoration system evolved before the msm1-type cytoplasm. In the
      nuclear genotype near-isogenic with either 'Adorra' or 'Riso 1508', msm1 plants
      heterozygous for Rfm1a produced 98.6 or 98.5% of the protein content in the
      respective recurrent pollen parent varieties. The amino acid compositions of the
      derivatives differed little from those of the varieties. In the derivatives, a
      consistent decrease was found in tryptophan, and consistent increases in
      isoleucine, phenyalanine, lysine, histidine, and arginine. In relation to glucose
      consumption, the bioenergetic cost calculated for the amino acid patterns found
      in the restored msm1 derivatives was slightly higher than that for the near
      isogenic pollen parent varieties. The results suggest that the restorer gene in
      the heterozygous state normalizes the physiology of msm1 cytoplasm to a great
      extent. 

PMID- 24301093
TI  - Analysis of the plastid DNA in an Oenothera plastome mutant deficient in ribulose
      bisphosphate carboxylase.
AB  - Plastid DNA of the light green Oenothera plastome mutant sigma, from plastome I,
      which is deficient in ribulose bisphosphate carboxylase, has been compared with
      wild-type chloroplast DNA from plastome I and the related plastome IV. For this,
      double digestions with the restriction endonucleases Sal I, Pst I and Kpn I were
      used. Chloroplast DNA from plastomes I and IV differs in the sizes of several
      fragments, with the changes being from under 0.1 to about 0.6 Md in size. In the
      cleavage patterns of the mutant DNA compared to the wild-type DNA from plastome
      I, the only differences observed are two possible deletions of less than 0.1 Md
      from a fragment known to partly cover the genes for the ribosomal RNAs and from a
      fragment located in the small single-copy region of the molecule. It is concluded
      that the ribulose bisphosphate carboxylase deficiency in this mutant is not
      caused by a major deletion in the plastid DNA. 

PMID- 24301094
TI  - Influence of early pregnancy on reproductive rate in lines of mice selected for
      litter size.
AB  - The influence of male-induced early puberty on female reproductive rate was
      determined in three lines of mice differing in litter size and body weight. The
      lines originated from a single base population and had undergone 20 generations
      of selection for the following criteria: large litter size at birth (L(+)), large
      litter size and small 6-week body weight (L(+)W(-)), or small litter size and
      large 6-week body weight (L(-)W(+)). Females were paired with a mature intact
      male of the same line at 3, 5 or 7 weeks of age. Mean mating age, averaged over
      lines, was 26.5 +/- .3, 38.3 +/- .3 and 52.7 +/- .3 days. Exposure to a mature
      male accelerated female sexual maturation in each line. When contrasted with
      their sibs mated at a later age, early-pregnant females from each line exhibited
      a decline in one or more component of reproductive performance, suggesting that
      the physiological state of the very young female was not optimum for normal
      pregnancy. In comparisons of early and later mating ages, all three lines showed
      a decreased littering rate at first mating, number born alive, and individual
      birth weight of progeny adjusted for litter size; L(+) and L(+)W(-) mice showed
      an increased perinatal mortality rate; L(+) and L(-)W(+) had a reduction in
      litter size at birth. When the L(+), L(+)W(-) and L(-)W(+) lines were compared
      with an unselected strain and a line selected for high postweaning gain in
      similar experiments, a genotype by environment interaction was apparent since all
      lines did not respond in a similar manner to early mating. The line ranking for
      litter size at birth for each age at male-exposure was L(+)>L(+)W(-)>L(-)W(+),
      despite the significant line by age interaction. When litter size was adjusted by
      covariance for body weight at mating, the significant effects of age at male
      exposure and line by age interaction were eliminated. All fertile females were
      remated after they had weaned their first litter to obtain information on litter
      size in parity two. Line differences in litter size at birth and number born
      alive were uniform across parities. An age by parity interaction was evident
      since the decreased fecundity at younger ages of male exposure in the L(+) and L(
      )W(+) litters of parity one was not evident in parity two. Litter feed efficiency
      during first parity gestation was defined as litter birth weight divided by
      either cumulative feed intake of the dam from mating to parturition (GEI) or
      cumulative feed intake from weaning to parturition (GEII). The ranking of lines
      for GEI and GEH was L(+)> L(+)W(-)>L(-)W(+), but when feed efficiency was
      adjusted for littering rate, L(+)W(-) and L(-)W(+) were not significantly
      different. With regard to age at mating, the ranking for GEI (7 wk > 5 wk > 3 wk)
      was reversed from GEII (3 wk >5 wk > 7 wk) and these significant differences were
      maintained after adjustment for littering rate. 

PMID- 24301095
TI  - Sister chromatid exchanges and chromosomal aberrations in 5-aminouracil
      synchronized cells.
AB  - 5-AU-synchronized cells of Allium cepa L.meristems show increased yields of
      chromosomal aberrations as well as SCE's. However, although a caffeine post
      treatment increases the frequency of 5-AU-induced abnormal ana-telophases, it has
      a negligible influence on the 5-AU-induced SCE's. These results strongly suggest
      that the mechanisms through which the 5-AU-induced DNA damage is transformed into
      chromosomal aberrations and SCE's are at least partly different. 

PMID- 24301096
TI  - Investigations on the relations within the family papilionaceae on the basis of
      electrophoretic banding patterns.
AB  - Gel electrophoretic investigations were made on the seed albumins of several
      members of the family Papilionaceae. Relationships were found with taxa of a
      lower order i.e. between mutants, varieties and subspecies. More distantly
      related ones, for example species of the same genus or species of different
      genera, did not show similarities. Thus, it was concluded that the albumin
      banding pattern is only suitable for studying phylogenetic and taxonomic problems
      if the material under investigation is not too distantly related. 

PMID- 24301097
TI  - Inheritance of resistance to yellow mosaic virus in blackgram (Vigna mungo (L.)
      Hepper).
AB  - The inheritance of resistance to mungbean yellow mosaic virus (MYMV) was studied
      in blackgram (Vigna mungo (L.) Hepper). The highly resistant donors Pant U-84 and
      UPU-2 and a highly susceptible line, UL-2, their F1's, F2's and backcrosses were
      grown with spreader located every 5 to 6 rows. The resistance was found to be
      digenic and recessive in all the crosses and free from cytoplasmic effect. 

PMID- 24301098
TI  - Chromosome location of two isozyme loci in Lolium perenne using primary
      trisomics.
AB  - Primary trisomics were used to locate the structural loci coding for particular
      forms of the dimeric enzymes phosphoglucoisomerase and glutamate oxaloacetate
      transaminase in Lolium perenne. The polymorphy of these loci enabled triallelic
      trisomics to be produced. Each locus could thus be directly assigned to a
      particular chromosome without the need to examine segregant progeny. The loci for
      GOT/3 and PGI/2 were found to be located on chromosomes 2 and 6 respectively. 

PMID- 24301099
TI  - Brentuximab vedotin followed by allogeneic transplantation as salvage regimen in
      patients with relapsed and/or refractory Hodgkin's lymphoma.
AB  - Patients with relapsed or refractory Hodgkin lymphoma (RR-HL) have poor outcomes.
      Brentuximab vedotin (BV), an antibody-drug conjugate comprising an anti-CD30
      antibody conjugated to the potent anti-microtubule agent, monomethyl auristatin
      E, induces high tumour responses with moderate adverse effects. In a
      retrospective study, we describe objective response rates and subsequent
      allogeneic stem cell transplantation (allo-SCT) in patients with RR-HL treated by
      BV in a named patient program in two French institutions. Twenty-four adult
      patients with histologically proven CD30(+) RR-HL treated with BV were included
      from July 2009 to November 2012. Response to BV treatment was evaluated after
      four cycles. Eleven patients were in complete response (45.8%), while five
      patients were in partial response (20.8%), with an overall response rate of
      66.6%. Eight patients failed to respond to BV (33.3%). All of the responding
      patients could receive consolidation treatment after BV: three patients underwent
      autologous stem cell transplantation (auto-SCT), three patients received a tandem
      auto-SCT/allo-SCT, nine patients received allo-SCT and one patient was treated
      with donor lymphocyte infusion. We found no treatment-related mortality at day
      100 among the 12 patients who underwent BV following by allogeneic
      transplantation. With a median follow-up of 20 months (range 10.5-43.2), none of
      them relapsed or died. BV followed by allo-SCT represents an effective salvage
      regimen in patients with RR-HL.

PMID- 24301101
TI  - Partnerships for prevention in the human services.

PMID- 24301100
TI  - Hydrogenase biomimetics: Fe2(CO)4(MU-dppf)(MU-pdt) (dppf = 1,1'
      bis(diphenylphosphino)ferrocene) both a proton-reduction and hydrogen oxidation
      catalyst.
AB  - Fe2(CO)4(MU-dppf)(MU-pdt) catalyses the conversion of protons and electrons into
      hydrogen and also the reverse reaction thus mimicing both types of binuclear
      hydrogenase enzymes. 

PMID- 24301102
TI  - Analysis of the knowledge base of primary prevention.
AB  - Primary prevention has recently emerged as a top priority on the nation's agenda
      in the social-psychological as well as in the medical arena. This paper examines
      the knowledge base on which prevention efforts might be founded. The results
      indicate that conventional published data bases are extremely deficient in
      preventive materials, and computer-based information systems are no better.
      Implications of these findings for primary prevention are discussed. 

PMID- 24301103
TI  - An unorthodox proposal for funding primary prevention.
AB  - Examining the literature in opposition to primary prevention finds that a major
      issue is the unwillingness of treatment advocates to share funding with primary
      prevention advocates. The author describes a model of financing prevention
      programs through the private sector, explains the methods necessary to implement
      the model, and provides three examples of prevention initiatives where the model
      can be applied. The paper ends with a discussion of the model's strengths and
      weaknesses. 

PMID- 24301104
TI  - Toward a systems-ecological approach to the prevention of adolescent alcohol
      abuse.
AB  - Findings from a questionnaire survey of adolescent drinkers are discussed in
      terms of developmental trends in alcohol and drug use, prevalence of drinking
      problems and the psychosocial correlates of problem drinking. Canonical
      correlation procedures are used to illustrate how multivariate statistical
      analysis can serve as a rational guide to the derivation of prevention goals and
      the formulation of prevention strategies. The basic elements of a "systems
      ecological" approach are then presented as a conceptual basis for prevention
      strategies designed to meet these goals. 

PMID- 24301105
TI  - Patterns of cooperation of child psychiatry with other departments in hospitals.
AB  - Four patterns of child psychiatrist cooperation which have implications for
      prevention are described: Autonomous Psychiatric Unit; Consultation;
      Collaboration; and Executive Partnership. These represent a gradient of
      increasing participation of psychiatrists inside the other department in the
      treatment of patients, in case responsibility, and in administrative authority
      over the service system. 

PMID- 24301106
TI  - Student team learning: Preventing the flocking and feathering of delinquents.

PMID- 24301107
TI  - Program development vs research: Which first? Dr. Bill Hollister, presents the
      issue Drs. Ruth Knee, Bernard Bloom, and Eli Bower-The replies.

PMID- 24301108
TI  - Primary prevention program clearninghouse psychology department-Dewey hall
      University of Vermont, Burlington, VT 05405.

PMID- 24301110
TI  - Cortical cell fluxes and transport to the stele in excised root segments of
      Allium cepa L. : IV. Calcium as affected by its external concentration.
AB  - From compartmental analysis of radioisotope elutin measurements, fluxes of Ca(2+)
      were estimated for cortical cells in root segments of onion, Allium cepa L.,
      relative to complete nutrient solutions containing a range of calcium
      concentrations ([Ca0]) from 2 MUeq l(-1) to 20 meq l(-1), increasing in 10-fold
      steps for Ca(2+). Except for the calcium counter-ion (usually NO 3 (-) ,
      sometimes Cl(-) at the highest [Ca0]), the composition of the nutrient solution
      was other-wise the same at all calcium concentrations. Compartmental analysis
      indicated that the cytoplasm had a high content of exchangeable Ca(2+) but, in
      the light of evidence from animal studies, ionic activity of calcium in the
      cytoplasm was assumed to be no greater than 0.002 MUeq ml(-1). With the Ussing
      Teorell flux equation as the criterion, it was concluded that at all values of
      [Ca0] tested, Ca(2+) entered the cytoplasm passively and was actively pumped back
      into the external solution. Entry of calcium to the vacuole from the cytoplasm
      was active in all cases. The conclusions regarding the character of ion transport
      across the plasmalemma were the same as when the whole calcium content of the
      cytoplasm was taken to contribute to the ionic activity. However, the
      electrochemical activity gradient was very much steeper than formerly estimated.
      Calcium was transported to the stele in proportion to the calcium content of the
      cytoplasm and moved in the xylem almost exclusively in the basipetal direction. 

PMID- 24301111
TI  - Transport of assimilates in the developing caryopsis of rice (Oryza sativa L.) :
      The pathways of water and assimilated carbon.
AB  - The movement of water in the dorsal region of the developing rice caryopsis was
      studied using solutions of the heavy metals lanthanum and uranium. In the
      electron microscope electron-opaque deposits were confined to the cell walls of
      the pigment strand indicating that this is the main route for the water which
      enters and leaves the caryopsis during grain filling. The pathway of assimilates
      into the developing caryopsis was examined using isolated caryopses which had
      taken up solutions of fluorescent dyes and also by autoradiography of caryopses
      which had transported (14)C-labelled assimilates in vivo. The results show that
      assimilates unloaded from the phloem move through the pigment strand and
      circumferentially via cells of the nucellus before entering the endosperm. A
      scheme is presented for the interrelations of water and assimilate transport
      during grain filling. 

PMID- 24301112
TI  - Low and high voltage electron microscopy of mitosis and cytokinesis in maize
      roots.
AB  - The structure and distribution of cytoplasmic membranes during mitosis and
      cytokinesis in maize root tip meristematic cells was investigated by low and high
      voltage electron microscopy. The electron opacity of the nuclear envelope and
      endoplasmic reticulum (ER) was enhanced by staining the tissue in a mixture of
      zinc iodide and osmium tetroxide. Thin sections show the nuclear envelope to
      disassemble at prophase and become indistinguishable from the surrounding ER and
      polar aggregations of ER. In thick sections under the high voltage electron
      microscope the spindle is seen to be surrounded by a mass of tubular (TER) and
      cisternal (CER) endoplasmic reticulum derived from both the nuclear envelope and
      ER, which persists through metaphase and anaphase. At anaphase strands of TER
      traverse the spindle between the arms of the chromosomes. The octagonal nuclear
      pore complexes disappear by metaphase, but irregular-shaped pores persist in the
      membranes during mitosis. It is suggested that these form a template for pore
      complex reformation during telophase. Phragmoplast formation is preceded by an
      aggregation of TER across the spindle at anaphase. Evidence is presented to
      suggest that the formation of the desmotubule of a plasmodesma is by the
      squeezing of a strand of endoplasmic reticulum between the vesicles of the cell
      plate. 

PMID- 24301113
TI  - Redox modulation of a phosphatase from Anacystis nidulans.
AB  - Ascorbic acid (AA) increased the phosphatase activity (pH 6.8) in 10,000 g
      supernatants from Anacystis nidulans. The enzyme activated by AA was deactivated
      by dehydroascorbic acid (DHAA). The modulation by AA/DHAA of phosphatase activity
      in Anacystis appears to be specific; a number of other redox compounds, known to
      modulate other enzymes, had no effect on the Anacystis phosphatase. A purified
      phosphatase preparation from Anacystis was also deactivated by DHAA. In contrast,
      the purified enzyme was not activated by AA, suggesting that a factor mediating
      the effect of AA was lost during purification. Another factor was found to
      protect the purified phosphatase against deactivation by DHAA. The enzyme was
      characterized as a phosphatase with a broad substrate specificity, an apparent
      molecular weight of 19,000, and a pH optimum of 6.0-7.0. Dialysis of the enzyme
      preparation against EDTA abolished the phosphatase activity which could be
      restored by Zn(2+) ions and partially restored by Co(2+) ions. Crude extracts
      also contained a latent enzyme, the phosphatase activity of which could be
      detected in the presence of Co(2+) ions only. Zn(2+) ions did not activate this
      enzymatically inactive protein. The Co(2+)-dependent phosphatase had an apparent
      mol. wt. of 40,000, a broad substrate specificity, and an alkaline pH-optimum.
      Infection of Anacystis cultures by cyanophage AS-1 resulted in a decrease in
      phosphatase activity. The enzyme present in 10,000 g supernatants from infected
      cells could not be modulated by the AA/DHAA system. 

PMID- 24301114
TI  - Modulation of the number of membrane-bound auxin-binding sites during the growth
      of batch-cultured tobacco cells.
AB  - We studied the modulation of the number of membrane-bound naphthaleneacetic acid
      (NAA)-binding sites during the growth cycle of tobacco cells in batch culture.
      Both cell number and specific NAA-binding increased exponentially, but at
      different rates and for different periods. This caused a characteristic
      modulation of the number of binding sites per cell during the growth cycle:
      During the first day of the lag phase this number decreased; in the exponential
      phase it rose markedly, and in the stationary phase it was constant. 

PMID- 24301115
TI  - Protein biosynthetic capacity in the endosperm tissue of ripening castor bean
      seeds.
AB  - Endosperm tissue was excised from Ricinus communis plants at different stages
      during seed maturation. The various stages were characterized on the basis of
      total RNA, protein and lipid content. Polyadenylated RNA was recovered from the
      total RNA by affinity chromatography on oligo(dT)cellulose. With the exception of
      that isolated from dry seeds, this poly(A(+)) RNA actively programmed protein
      synthesis in cell-free systems containing either wheat germ S30 extracts or
      nuclease treated rabbit reticulocyte lysates at each developmental stage
      examined. Translational products were separated electrophoretically and were
      visualized by fluorography. The capacity to synthesize protein was also estimated
      during 'in vivo' labelling studies. Developmental changes in the capacity of
      maturing endosperm tissue to synthesize a characteristic protein, R. communis
      agglutinin, were followed by immunoprecipitating this protein from the total 'in
      vitro' products synthesized at various stages. Endoplasmic reticulum membranes
      were isolated from maturing endosperm tissue by sucrose density gradient
      centrifugation. The role of the endoplasmic reticulum (ER) in protein
      glycosylation was indicated by (a) localizing the enzymes catalysing the
      incorporation of N-acetylglucosamine and mannose into mono- and oligosaccharide
      lipid and into glycoprotein, (b) localizing particulate (3)H-labelled
      glycoprotein amongst cellular fractions prepared from endosperm tissue which had
      been incubated with [(3)H]N-acetylglucosamine. 

PMID- 24301116
TI  - Control of enzyme activities in cotton cotyledons during maturation and
      germination : III. In-vitro embryo development in the presence of abscisic acid.
AB  - Cotton (Gossypium hirsutum L.) embryos excised from bolls 38-43 d after anthesis
      and cultured in vitro for 4 d on a nutrient agar medium containing 3.8 MUM
      abscisic acid (ABA) developed enzyme activity and accumulated insoluble protein,
      neutral lipid, and dry weight similar to embryos maturing on the plant. Inclusion
      of ABA in the medium prevented precosious germination and allowed continued
      increases in catalase, malate dehydrogenase, citrate synthase, aspartate
      aminotransferase, and beta-oxidation enzyme activities as well as de-novo
      synthesis of malate synthase. Isocitrate lyase activity was not detectable in ABA
      cultured embryos nor normally-developed embryos. Omission of sucrose from the
      medium resulted in near-doubling of the development of malate synthase activity,
      with minimal effects on the other enzyme activities. Addition of Actinomycin D,
      cordycepin, or cycloheximide to ABA-containing cultures did not overcome the
      observed inhibition of germination, but severely reduced both the appearance of
      new malate synthase activity and further production of other related enzyme
      activities. Thus, development of these enzyme activities in the presence of ABA
      appears dependent on transcription and translation, while inhibition of
      germination by ABA at this stage of development is not sensitive to the RNA- and
      protein-synthesis inhibitors. The results indicate that ABA does not prevent
      vivipary by suppressing translation of m-RNAs coding for isocitrate lyase and its
      companion enzymes, as previously proposed. 

PMID- 24301117
TI  - Red-light- and gibberellic-acid-enhanced alpha-galactosidase activity in
      germinating lettuce seeds, cv. Grand Rapids : Control by the axis.
AB  - Dry lettuce (Lactuca sativa L.) "seeds" (achenes) contain alpha-galactosidase (EC
      3.2.122) at a level which is maintained in the imbibed dormant state in darkness.
      Both red light (R) and gibberellic acid promote an increase in enzyme activity
      several hours prior to the completion of germination. Germination and enzyme
      activity are not essentially linked, however, for the latter can increase while
      the former is inhibited. alpha-Galactosidase activity increases within the
      cotyledons and the endosperm following R stimulation, but the axis is essential
      to perceive the stimulus and to promote and maintain the increase in enzyme
      activity. A diffusible factor (or factors) is produced by and-or released from
      irradiated axes, and it migrates to the cotyledons (and possibly endosperm) to
      promote the increase in alpha-galactosidase activity. Gibberellic acid,
      particularly in the presence of benzyladenine, can replace the requirement for
      irradiated axes. 

PMID- 24301118
TI  - Short-term kinetics of elongation growth of gibberellin-responsive lettuce
      hypocotyl sections.
AB  - The short-term kinetics of growth of the excised lettuce (Lactuca sativa L.)
      hypocotyl were characterized with respect to the effects of gibberellic acid
      (GA3), indole-3-acetic acid (IAA), KCl and pH. A Hall-device-based, miniaturized,
      linear displacement transducer was developed to measure the growth of 2-mm
      hypocotyl sections with 1-MUm resolution. Following treatment with GA3, a lag
      time of less than 10 min was typically followed by an increase in growth rate
      with two acceleration phases, reaching a final elevated rate within about 1 h.
      The kinetics of the response to GA1, a mixture of GA4 and GA7, and GA9 were
      similar to the response to GA3. There was no response to IAA treatment either in
      the presence or absence of GA3. KCl alone had no effect on the growth rate, but
      caused an increase in rate when added after GA3, with a lag time of usually less
      than 1 h. Responses to pH changes had lag times of a few minutes in all cases. A
      shift from H2O to pH 6 buffer inhibited growth, while a shift from H2O to pH 4
      buffer resulted in a transient increase to a rate comparable to that induced by
      GA3. A shift from pH 6 to pH 5 caused an increase in growth rate, followed by a
      gradual decline to an H2O control rate after more than an hour. The responses to
      GA3 at pH 4 and pH 5 were similar to that found for addition of GA3 to water
      controls. 

PMID- 24301119
TI  - Calcium and gibberellin-induced elongation of lettuce hypocotyl sections.
AB  - The relationship between calcium ions and gibberellic acid (GA3)-induced growth
      in the excised hypocotyl of lettuce (Lactuca sativa L.) was investigated. The
      short-term kinetics of growth responses were measured using a linear displacement
      transducer. Test solutions were added either as drops to the filter paper on
      which the hypocotyl stood ("non-flow-past") or by switching solution flowing past
      the base of hypocotyl ("flow-past"), resulting in differences in growth behavior.
      Drops of CaCl2 added at a high concentration (10 mM) inhibited growth within a
      few minutes. This inhibition was reversed by ethylenediaminetetraacetic acid
      (EDTA). Drops of EDTA or ethyleneglycol-bis(2-aminoethylether)-tetraacetic acid
      caused a rapid increase in growth rate. Growth induced by EDTA was not further
      promoted by GA3. A continuous H2O flow resulted in growth rates comparable to
      those in response to GA3. Addition of CaCl2 to the flow-past medium inhibited
      growth and this inhibition was reversed by a decrease in CaCl2 concentration. The
      growth rate was found to be a function of CaCl2 concentration. When a constant
      CaCl2 concentration was maintained by the flow-past medium, a shift in pH from
      5.5 to 4.25 had no obvious effect on hypocotyl elongation. Gibberellic acid was
      found to reverse the inhibitory effect of CaCl2, causing an increase in growth
      rate similar to that found previously when GA3 was added to hypocotyls grown in
      H2O under non-flow-past conditions. We propose that gibberellin controls
      extension growth in lettuce hypocotyl sections by regulating the uptake of Ca(2+)
      by the hypocotyl cells. 

PMID- 24301120
TI  - Regulation of RNA synthesis in higher plant cells by the action of a nucleoside
      triphosphatase.
AB  - The influence of nucleoside triphosphates in relation to divalent cations on RNA
      synthesis of cells from a suspension culture from parsley was investigated. The
      data obtained from experiments with isolated nuclei and with an in vitro system
      with highly purified RNA polymerase I were compared with a chromatin-bound
      nucleoside triphosphatase activity within the nucleus. The results might suggest
      a regulatory role of the nucleoside triphosphatase activity in RNA synthesis. 

PMID- 24301121
TI  - (14)C fixation, metabolic labeling patterns, and translocation profiles during
      leaf development in Populus deltoides.
AB  - The incorporation of photosynthetically fixed (14)CO2 and the distribution of
      (14)C among the main chemical constituents of laminae and petioles were examined
      in cottonwood (Populus deltoides Bartr. ex Marsh.) leaves ranging in age from
      Leaf Plastochron Index (LPI) 3 (about one-quarter to one-third expanded) to LPI
      30 (beginning of senescence). In addition, carbon flow among chemical fractions
      and translocation from leaves of LPI 7 and 14 were examined periodically up to 24
      h after labeling. Specific activity of (14)C (on dry-weight basis) increased in
      developing laminae to full leaf expansion, decreased in the mature leaves to LPI
      16, then remained constant to LPI 30. In developing leaves (LPI 3-5), after 2 h,
      most of the (14)C was found in protein, pigments, lipids, and other structural
      and metabolic components necessary for cell development; only 28% was in the
      sugar fraction of the lamina. In fully expanded leaves (LPI 6-8), after 2 h, the
      sugar fraction contained 50-60% and about 90% of fixed (14)C in the lamina and
      the petiole, respectively. In a pulsechase "kinetic series" with recently mature
      leaves, 60% of the (14)C was found in the sugar fraction after 15 min of (14)CO2
      fixation. Over the 24-h translocation period, (14)C decreased in sugars to 23%
      and increased in the combined residue fraction (protein, starch, and structural
      carbohydrates) to about 60% of the total activity left in the lamina. Within 24 h
      after labeling, the turnover of (14)C-organic acids,-sugar, and-amino acids
      (either metabolzed or translocated from the leaf) was 30, 70 and 80%,
      respectively, of that initially incorporated into these fractions by a leaf at
      LPI 7 (turnover was 55% of (14)C-organic acids, 80% of (14)C-sugar, and 95% of
      (14)C-amino acids at LPI 14). Anatomical maturity in cottonwood leaves is closely
      correlated with physiological maturity and with production of translocatable
      sugar. 

PMID- 24301122
TI  - Effect of high-light treatments in inducing photoinhibition of photosynthesis in
      intact leaves of low-light grown Phaseolus vulgaris and Lastreopsis microsora.
AB  - Photoinhibition studies, using gas-exchange techniques, were conducted with
      leaflets of Phaseolus vulgaris L. plants that were grown under low photonfluence
      rates. Comparative measurements were made on attached, intact leaflets and in
      subsequently isolated chloroplasts. Photoinhibition studies were also conducted
      with attached fronds of the deep-shade fern Lastreopsis microsora (Endl.)
      Tindale. Leaflets of lowlight-grown Phaseolus vulgaris and fronds of the shade
      fern were found to be subject to similar photoinhibition when exposed to photon
      fluence rates in excess of those at which they were grown. Photoinhibition
      following exposure to a photon fluence-rate approximating full sunlight is
      manifested as a reduction in the capacity for both light-saturated and light
      limited carbon uptake and is reflected at the chloroplast level as substantial
      inhibition of electron flow through photosystem (PS) II, with little effect on PS
      I. The extent of photoinhibition is markedly dependent on the length of exposure
      to a high-light regime and on the actual photon-fluence rate maintained during
      treatment. A greater degree of photoinhibition is evident if carbon metabolism is
      prevented by the removal of CO2 than when maximum rates of CO2 uptake prevail
      throughout the exposure to a high photonfluence rate. Apparently a certain level
      of CO2 turnover is beneficial in providing a sink for photochemically generated
      energy. When leaf material is exposed to photon-fluence rates well in excess of
      the rate present during growth apparently the potentials of the various
      biophysical and photochemical means of dissipating excitation energy are exceeded
      and photoinhibition of photosynthesis results. 

PMID- 24301123
TI  - Detection of the Nicotiana rustica chloroplast genome coding for the large
      subunit of Fraction I protein in a somatic hybrid in which only the N. tabacum
      chloroplast genome appeared to have been expressed.
AB  - Nine plants were produced from anthers of a somatic hybrid which had been
      obtained by fusion of Nicotiana tabacum L. and N. rustica L. protoplants. As
      determined by electrofocusing, the Fraction I protein of the original somatic
      hybrid had largesubunit polypeptides exclusively of the N. tabacum type. Two of
      the plants regenerated from anthers contained Fraction-I-protein large subunits
      exclusively of the N. rustica type. Since each plant was regenerated from a
      single cell, the somatic hybrid must have had cells containing both the N.
      tabacum and N. rustica chloroplast genome although the latter was not expressed.
      Possibilities to account for this non-expression of a chloroplast genome in the
      somatic hybrid are discussed. 

PMID- 24301124
TI  - Molecular characterization of a wound-inducible inhibitor I gene from potato and
      the processing of its mRNA and protein.
AB  - Genomic blotting of restriction fragments of Russet Burbank DNA indicated that at
      least 6 copies of Inhibitor I are present in the tetraploid potato genome. A
      library of potato genes in bacteriophage lambda was screened for the presence of
      Inhibitor I genes using a wound-inducible tomato Inhibitor I cDNA as a
      hybridization probe. One phage with an insert of 13.1 kb was isolated that
      hybridized most strongly with the probe. A 4.2 kb Eco RI fragment containing the
      gene was isolated from the clone and 2.2 kb region was sequenced that included
      about 800 bp of both the 5' and 3' regions. The gene contained two introns of 479
      and 417 bp respectively, and the splice junctions were typical of other
      eukaryotic genes. Putative TATAA and CAAT boxes were identified. The nucleotide
      sequence, when compared with a wound-inducible tomato Inhibitor I cDNA, exhibited
      over 90% identity. The gene codes for a prepro-Inhibitor I protein of 96 amino
      acids. The putative pre-sequence of 19 amino acids, differs in only one residue
      from that of tomato Inhibitor I. The potato pro-sequence, however, is lacking a
      tetrapeptide that is found in the tomato pro-sequence in the region of pro
      peptide processing. This deletion, together with a substitution of a Gln for a
      Leu (4 residues toward the N terminus) provides an explanation for the
      differences at the N-termini between tomato and potato Inhibitor I natural
      proteins by providing different processing sites in the two pro-inhibitors. Thus,
      amino acid sequence differences between the N termini of tomato and potato
      Inhibitor I are easily explained by the mutational events. The different proposed
      pro-processing sites of the tomato and potato inhibitors suggest that a
      processing protease may be present in the vacuole with a specificity for Asn-X
      and Gln-X bonds. 

PMID- 24301125
TI  - Ri-plasmid as a helper for introducing vector DNA into alfalfa plants.
AB  - Genetic engineering of legumes and other important dicotyledonous plants is
      limited because of the difficulty of regenerating plants via cell culture. Since
      a considerable number of crop plants can be regenerated only from root culture,
      the introduction of foreign genes into Agrobacterium rhizogenes-induced hairy
      roots may expand the list of crop plants that could be genetically engineered.
      Here we report genetic transformation of alfalfa (Medicago sativa L.), a valuable
      forage legume, using a virulent strain of Agrobacterium rhizogenes containing, in
      addition to its Ri-plasmid, a binary vector containing a nopaline synthase gene.
      Plant cells transformed by this vector can be easily identified by their ability
      to produce nopaline. Transformed alfalfa plants were recovered from A. rhizogenes
      induced hairy roots. These transgenic plants were characterized by normal leaf
      morphology and stem growth but a root system that was shallow and more extensive
      than normal. These plants were also fertile, set seeds upon self-pollination and
      outcrossing. Nopaline was detected in R1 progeny. Southern blot analysis
      confirmed the presence of multiple copies of T-DNAs from the Riplasmid in the
      plant genome in addition to the vector T-DNA. 

PMID- 24301126
TI  - Ribosomal DNA methylation in a flax genotroph and a crown gall tumour.
AB  - The methylation patterns of two flax lines are described. One, a genotroph S1,
      has 800 rNA genes per haploid cell while FT37/1, a crown gall tumour incited on
      S1, has only 300. Using the enzymes EcoRII, BstNI and ApyI to assess CXG
      methylation and HpaII and MspI for CG, we show that the methylation patterns of
      the rDNAs of both lines are identical. Both lines contain 3 fractions; the first
      contains repeats that are methylated at all sites examined and the second has
      some unmethylated sites. The third fraction contains repeats that are fully
      methylated but contain a discrete hypomethylated site at the 5' end of the pre
      rRNA. The number of repeats which show these hypomethylated sites is constant in
      both lines despite the copy number difference. These may represent the active
      rRNA gene repeats. 

PMID- 24301127
TI  - Regulation of levels of nuclear transcripts for C4 photosynthesis in bundle
      sheath and mesophyll cells of maize leaves.
AB  - In vitro translation of polyA(+) mRNAs isolated from purified maize bundle sheath
      and mesophyll cells results in the production of distinctive, cell-specific
      polypeptides. Immunoprecipitation experiments show that translatable polyA(+)
      mRNAs for phosphoenolpyruvate carboxylase (PEPC), pyruvate orthophosphate
      dikinase (PPDK) and NADP-malate dehydrogenase (MDH) are prominent in mesophyll
      but not bundle sheath cells. On the contrary, those for sedoheptulose-1,7
      bisphosphatase (SBP), fructose-1,6-bisphosphatase (FBP), NADP-malic enzyme (ME)
      and the small subunit of ribulose-1,5-bisphosphate carboxylase (RuBPC SS) are
      present only in bundle sheath cells. Moreover, polyA(+) mRNAs encoding the 33 kD,
      23 kD and 16 kD polypeptides of the oxygen-evolving complex (OE33, OE23 and OE16)
      and the light-harvesting chlorophyll a/b binding protein of photosystem II (LHCP
      II) are much more abundant in mesophyll than in bundle sheath cells. Northern
      blot analyses with cDNA clones of PEPC, PPDK, ME, RuBPC SS, OE33, OE23, OE16 and
      LHCP II are consistent with the conclusion that the cell-specific expression of
      these genes is regulated at the RNA level. The RNA level differences are
      especially dramatic in dark-grown maize seedlings after illumination for 24 h. 

PMID- 24301128
TI  - Cloning and sequence analysis of a cDNA encoding a Brazil nut protein
      exceptionally rich in methionine.
AB  - The primary amino acid sequence of an abundant methionine-rich seed protein found
      in Brazil nut (Bertholletia excelsa H.B.K.) has been elucidated by protein
      sequencing and from the nucleotide sequence of cDNA clones. The 9 kDa subunit of
      this protein was found to contain 77 amino acids of which 14 were methionine
      (18%) and 6 were cysteine (8%). Over half of the methionine residues in this
      subunit are clustered in two regions of the polypeptide where they are
      interspersed with arginine residues. In one of these regions, methionine residues
      account for 5 out of 6 amino acids and four of these methionine residues are
      contiguous. The sequence data verifies that the Brazil nut sulfur-rich protein is
      synthesized as a precursor polypeptide that is considerably larger than either of
      the two subunits of the mature protein. Three proteolytic processing steps by
      which the encoded polypeptide is sequentially trimmed to the 9 kDa and 3 kDa
      subunit polypeptides have been correlated with the sequence information. In
      addition, we have found that the sulfur-rich protein from Brazil nut is
      homologous in its amino acid sequence to small water-soluble proteins found in
      two other oilseeds, castor bean (Ricinus communis) and rapeseed (Brassica napus).
      When the amino acid sequences of these three proteins are aligned to maximize
      homology, the arrangement of cysteine residues is conserved. However, the two
      subunits of the Brazil nut protein contain over 19% methionine whereas the
      homologous proteins from castor bean and rapeseed contain only 2.1% and 2.6%
      methionine, respectively. 

PMID- 24301129
TI  - DNase I hypersensitivity and expression of the Shrunken-1 gene of maize.
AB  - The local chromatin structure of the Shrunken-1 (Sh) gene of maize was probed by
      analyzing DNase I hypersensitivity. Sh encodes the gene for sucrose synthetase, a
      major starch biosynthetic enzyme, which is maximally expressed in the endosperm
      during seed maturation. In addition to general DNase I sensitivity, specific
      DNase I hypersensitive sites were identified in endosperm chromatin that mapped
      near the 5' end of the Sh gene. The pattern of hypersensitive sites and their
      relative sensitivity were altered in other non-dormant tissues that produce
      little or no enzyme. However, some changes in chromatin structure appear to be
      independent of Sh gene expression and may reflect general alterations associated
      with plant development. The chromatin structure of several sh mutations, induced
      by Ds controlling element insertions, was also analyzed. Although the insertions
      perturbed expression of the gene, there were no notable effects on local
      chromatin structure. 

PMID- 24301130
TI  - Transformation of carrot tissues derived from proembryogenic suspension cells: A
      useful model system for gene expression studies in plants.
AB  - A method is described for the high frequency transformation of carrot
      proembryogenic suspension culture cells by a non-oncogenic Ti-plasmid vector
      (pGV3850::1103) which carried a chimaeric kanamycin resistance gene (nos-NPT-II).
      Plants were regenerated efficiently from transformed material by somatic
      embryogenesis in the presence of kanamycin. Transformed tissues expressed readily
      detectable levels of both NPT-II and nopaline. NPT-II could be detected in total
      protein extracts by Western blotting. This analysis indicated that NPT-II was
      produced as a single, full length polypeptide. The T-DNA copy number in
      individually selected transformants was analysed by Southern blotting and ranged
      from 1-8 per diploid genome. The copy number and organization of the T-DNA was
      retained in plants regenerated from these transformants by somatic embryogenesis.
      These data suggested a clonal origin for the selected kanamycin resistant
      colonies. NPT-II expression levels appeared to be directly related to gene
      dosage. 

PMID- 24301131
TI  - Detection of CaMV gene I and gene VI protein products in vivo using antisera
      raised to COOH-terminal beta-galactosidase fusion proteins.
AB  - Specific antisera were prepared to the inclusion body protein (gene VI product)
      and the gene I product of cauliflower mosaic virus (CaMV). Translational fusions
      between the lacZ gene and gene VI or gene I were constructed by cloning the
      relevant DNA fragments into the expression vectors pUR290, pUR291 or pUR292.
      Large amounts of fusion protein were synthesized when the inserted DNA fragment
      was in frame with the lacZ gene of the expression vector. These fusion proteins
      were used to raise specific antisera to gene VI and gene I proteins of CaMV.
      Antiserum to the gene VI product detected a range of proteins in crude extracts
      and in a subcellular fraction enriched for virus inclusion bodies. This range of
      proteins was further shown to be related to gene VI by Staphylococcus aureus V8
      partial proteolysis. Antiserum to the gene I product detected viral specific
      proteins of 46, 42 and 38 K in preparations of CaMV replication complexes from
      infected plants but not in any other subcellular fraction. 

PMID- 24301133
TI  - Cost effectiveness of primary care referral to a commercial provider for weight
      loss treatment, relative to standard care: a modelled lifetime analysis.
AB  - BACKGROUND: Because of the high prevalence of overweight and obesity, there is a
      need to identify cost-effective approaches for weight loss in primary care and
      community settings. OBJECTIVE: To evaluate the long-term cost effectiveness of a
      commercial weight loss programme (Weight Watchers) (CP) compared with standard
      care (SC), as defined by national guidelines. METHODS: A Markov model was
      developed to calculate the incremental cost-effectiveness ratio (ICER), expressed
      as the cost per quality-adjusted life year (QALY) over the lifetime. The
      probabilities and quality-of-life utilities of outcomes were extrapolated from
      trial data using estimates from the published literature. A health sector
      perspective was adopted. RESULTS: Over a patient's lifetime, the CP resulted in
      an incremental cost saving of AUD 70 per patient, and an incremental 0.03 QALYs
      gained per patient. As such, the CP was found to be the dominant treatment, being
      more effective and less costly than SC (95% confidence interval: dominant to 6225
      per QALY). Despite the CP delaying the onset of diabetes by ~10 months, there was
      no significant difference in the incidence of type 2 diabetes, with the CP
      achieving <0.1% fewer cases than SC over the lifetime. CONCLUSION: The modelled
      results suggest that referral to community-based interventions may provide a
      highly cost-effective approach for those at high risk of weight-related
      comorbidities.

PMID- 24301135
TI  - In situ carbon coated LiFePO4/C microrods with improved lithium intercalation
      behavior.
AB  - LiFePO4/C microrods consisting of building blocks of interconnected nanoparticles
      surrounded by a thin and amorphous coating of carbon have been prepared by a
      customized hydrothermal method. Appreciable discharge capacity values of 168 mA h
      g(-1) at 0.1 C and 130 mA h g(-1) at 5 C rates have been exhibited by the
      currently synthesized LiFePO4/C cathode. The study enumerates the feasibility of
      exploiting the hydrothermal method to prepare an in situ carbon coated LiFePO4/C
      compound with tunable morphological properties and desirable electrochemical
      properties observed for up to 100 cycles at a 5 C rate. 

PMID- 24301136
TI  - Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient
      models.
AB  - Recent studies have shown the feasibility of estimating patient dose from a CT
      exam using CTDI(vol)-normalized-organ dose (denoted as h), DLP-normalized
      effective dose (denoted as k), and DLP-normalized-risk index (denoted as q).
      However, previous studies were limited to a small number of phantom models. The
      purpose of this work was to provide dose coefficients (h, k, and q) across a
      large number of computational models covering a broad range of patient anatomy,
      age, size percentile, and gender. The study consisted of 100 patient computer
      models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric
      models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age
      range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners
      from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM
      Definition Flash, Siemens Healthcare) were included. A previously-validated Monte
      Carlo program was used to simulate organ dose for each patient model and each
      scanner, from which h, k, and q were derived. The relationships between h, k, and
      q and patient characteristics (size, age, and gender) were ascertained. The
      differences in conversion coefficients across the scanners were further
      characterized. CTDI(vol)-normalized-organ dose (h) showed an exponential decrease
      with increasing patient size. For organs within the image coverage, the average
      differences of h across scanners were less than 15%. That value increased to 29%
      for organs on the periphery or outside the image coverage, and to 8% for
      distributed organs, respectively. The DLP-normalized-effective dose (k) decreased
      exponentially with increasing patient size. For a given gender, the DLP
      normalized-risk index (q) showed an exponential decrease with both increasing
      patient size and patient age. The average differences in k and q across scanners
      were 8% and 10%, respectively. This study demonstrated that the knowledge of
      patient information and CTDIvol/DLP values may be used to estimate organ dose,
      effective dose, and risk index in abdominopelvic CT based on the coefficients
      derived from a large population of pediatric and adult patients.

PMID- 24301134
TI  - Association of leptin and insulin with childhood obesity and retinal vessel
      diameters.
AB  - OBJECTIVE: Childhood obesity is associated with an impaired retinal
      microcirculation. The aim of the study was to investigate the association between
      specific obesity-related biomarkers, physical fitness and retinal vessel
      diameters in school children. DESIGN AND SUBJECTS: We studied 381 children aged
      10-11 years (body mass index (BMI): 19.3+/-3.7 kg m(-2)) in a school-based
      setting. MEASUREMENTS: Anthropometric measurements and blood sampling were
      conducted using standard protocols for children. The serum biomarkers leptin,
      adiponectin, insulin as well as interleukin-6 (IL-6) were analyzed. Physical
      fitness was determined by a six-item-test battery and physical activity by use of
      a questionnaire. Central retinal arteriolar equivalent (CRAE), central retinal
      venular equivalent (CRVE) and the arteriolar-to-venular diameter ratio (AVR) were
      assessed with a non-mydriatic vessel analyzer (SVA-T) using a computer-based
      program. RESULTS: Compared with normal weight children (n=254), obese children
      (n=39) showed higher leptin (P<0.001), higher insulin (P<0.001), higher IL-6
      (P<0.001) and lower adiponectin levels (P=0.013). Obese children demonstrated
      wider CRVE (P=0.041) and lower AVR (P<0.001). Higher leptin levels were
      associated with wider CRVE (P=0.032) and lower AVR (P=0.010), that was BMI
      dependent. Insulin levels were associated with arteriolar (P=0.045) and venular
      dilatation (P=0.034) after adjustment for BMI. No significant associations
      between adiponectin levels, IL-6 levels, physical fitness or physical activity
      and retinal vessel diameter were observed. Lower leptin levels were independently
      correlated with higher physical fitness (r=-0.33; P<0.001). CONCLUSION: Leptin
      and insulin levels are associated with changes of the retinal microcirculation.
      Especially insulin seems to be a good target marker for the cardiometabolic risk
      assessment in children since elevated insulin levels are independently associated
      with microvascular end-organ alterations at an early stage. Lifestyle
      intervention studies are warranted to examine whether improvement of physical
      fitness or weight reduction can affect cardiometabolic risk markers and reverse
      alterations of the retinal microcirculation.

PMID- 24301137
TI  - Parental role in teenage driving.
AB  - Students in 75 high schools in seven states participated in a questionnaire
      survey. The results showed that high school students want to become licensed as
      soon as possible and that parents are important in teaching them to drive. Once
      licensed, the majority of students have their own cars, though they do not
      typically pay the majority of the costs. Seventy-one percent of licensed students
      who do not have their own cars reported that they can usually or always use a
      family car. Most students, particularly younger ones and females, reported that
      their parents expect them to conform to certain rules or restrictions when
      driving and when riding as passengers. The most common restrictions were that
      their parents asked them not to drive after drinking, to tell parents where they
      were going and with whom, and to be home at a certain time. Students were far
      less likely to report that their parents required that they wear seat belts. 

PMID- 24301138
TI  - Variables that discriminate bulimic from nonbulimic adolescent females.
AB  - The present study identified variables that discriminated bulimic (N=71) from
      nonbulimic (N=71) adolescent females within a high school setting. A discriminant
      function analysis identified six variables that significantly differentiated
      these two groups. These variables included disturbed eating attitudes, negative
      perceptions of weight and body image, depressive symptomatology, and alcohol use.
      Post hoct tests indicated that, compared to the nonbulimic girls, the bulimic
      adolescents were significantly more depressed, viewed themselves as significantly
      more overweight, used alcohol significantly more frequently, possessed
      significantly more disturbed eating attitudes, had a significantly greater
      discrepancy between their current and ideal weight, and felt it was significantly
      more important to achieve this ideal weight. The implications of these findings
      for the etiology and early identification of bulimia in adolescence are
      discussed. 

PMID- 24301139
TI  - A survey of adolescent military family members' self-image.
AB  - The Offer Self-Image Questionnaire was administered to 135 adolescent military
      family members, ages 13 through 18. The data suggest that the usual demands
      placed on the military family do not deter the adolescent from developing a
      healthy self-image. 

PMID- 24301140
TI  - Family relationships and social competence during late adolescence.
AB  - Data from a large sample of late adolescents was used to examine associations
      between family relationships (reported closeness to parents and siblings) and
      perceived social competence. Significant positive relationships were found
      between family bonds and the social competence measures, which included social
      self-esteem, instrumentality, expressiveness, shyness, and degree of
      satisfaction/ease in same- and opposite-sex peer relationships. There was no
      evidence of differential effects of sibling versus parent relationships upon
      adolescent social competence. 

PMID- 24301141
TI  - Family learning environment: The subjective view of adolescent males and females.
AB  - This study investigates sex differences in two aspects of family learning
      environment as subjectively viewed by adolescents: parents' educational
      expectations and relationships with parents. Analysis of the data collected from
      105 young Israeli adolescents (65 males and 40 females) shows sex differences in
      both aspects of family learning environment. These differences are (a) a negative
      relation between idealistic expectations and academic performance for females and
      a positive relation between realistic expectations and academic performance for
      males, and (b) a positive relation between estimated similarity with father and
      academic performance for females and a negative relation between social emotional
      relationship with father and academic performance for males. These sex
      differences are viewed in light of the greater complexity of female identity as
      it is related to low achieving females' perceived pressure to improve academic
      performance and high achieving females' feeling closer to their fathers. 

PMID- 24301142
TI  - Separation-individuation and ego identity status in New Zealand university
      students.
AB  - This study explores intrapsychic structures underlying Marcia's ego identity
      statuses in terms of separation-individuation patterns. It was hypothesized that
      achievement and moratorium adolescents would give greater evidence of
      intrapsychic differentiation on a projective measure of separation anxiety than
      would foreclosure or diffusion youths. Marcia's Ego Identity Status Interview and
      Hansburg's Separation Anxiety Test were administered to 80 female and 60 male
      volunteers at a New Zealand university. All were under 23 years of age. As
      predicted, high statuses showed less anxiety than secure attachment or
      detachment. Contrary to expectation, no differences among attachment styles
      appeared for low statuses. Difficulties in adapting the identity status interview
      to the New Zealand context may partially explain these results. A measure of
      intrapsychic differentiation provides a useful supplement to the identity status
      interview. 

PMID- 24301144
TI  - Somatic hybridization in Petunia : Part 2: heteroplasmic state in somatic hybrids
      followed by cytoplasmic segregation into male sterile and male fertile lines.
AB  - Two types of cytoplasmic hybrids were obtained by protoplast fusion. These
      contained either one or the other original parental nucleus and heteroplasmon, a
      mix of plasmons inducing cytoplasmic male sterility and fertility. In subsequent
      generations, following selfing, stable male sterile and male fertile lines
      segregated from single fertile cytoplasmic hybrid plants. These data demonstrated
      the existence of a heteroplasmic state in the somatic hybrids and the occurrence
      of cytoplasmic segregation of the heteroplasmon into homoplasmons following the
      first and the second meiotic cycles. 

PMID- 24301145
TI  - Chromosome replacement in mixed populations of compound-2L; free-2R and standard
      strains of Drosophila melanogaster : An example of unstable genetic isolation.
AB  - Crosses between compound-2L; free-2R (free-arm) and standard strains of
      Drosophila melanogaster produce two classes of inviable aneuploid hybrids in
      equal proportions: monosomic 2L and trisomic 2L. The lethal period for monosomics
      occurs during embryogenesis while the trisomics survive to late pupae. Since the
      hybrids are inviable, standard and free-arm strains within a mixed population
      remain genetically isolated. Genetic isolation in the absence of mating isolation
      offers an extreme example of unstable equilibrium. Relative fitness data indicate
      that an unstable equilibrium will be established between free-arm and standard
      strains at a ratio of 2.5?1. Indeed, in three cage experiments established at
      initial ratios of 3?1, free arms to standards, laboratory (Oregon R) or native
      (Okanagan S) standard strains were completely replaced in approximately 100 days
      by free-arm lines derived either from laboratory or from native genetic
      background. In contrast, one cage established at an initial ratio of 4?1 failed
      to show replacement and for 92 days remained at approximately the initial ratio.
      Subsequent genetic analysis of flies removed from this cage identified the
      presence of an anomalous strain through which genetic information was transferred
      reciprocally between the free-arm and standard lines. The second chromosomes
      carried by this strain consisted of a free-2R and a standard second on the right
      arm of which was attached a duplication for all of 2L. While the origin of the
      2L.2R+2L chromosome was uncertain, genetic and cytological examinations revealed
      that it represented the reciprocal crossover product expected from an exchange
      that generated a F(2R). Additional crosses disclosed that the transmission
      frequency of the asymmetrical pair of second chromosomes, as well as their right
      arm crossover products, was disproportionately in favor of the short arm. Since
      unequal transmission was invariably greater from female parents, this phenomenon
      was viewed as further evidence in support of the drag hypothesis. 

PMID- 24301146
TI  - Adaptive strategies in natural populations of Drosophila : Ethanol tolerance,
      desiccation resistance, and development times in climatically optimal and extreme
      environments.
AB  - Adult tolerance of ethanol vapour in a closed system containing 12% ethanol in
      solution, decreases in a cline from southern to northern Australia. However a
      Darwin population is more tolerant than predicted from its latitude. Ethanol
      tolerance races in Australia have almost certainly evolved within the last 100
      150 years, because of resource unavailability prior to that time. Within
      populations, variation among isofemale strains is lowest in the climatically
      extreme southern Melbourne (37 degrees S) and northern Darwin and Melville I. (11
      12 degrees S) populations. This suggests low resource diversity within extreme
      populations compared with the climatically less extreme Brisbane (28 degrees S)
      and especially Townsville (19 degrees S) populations. For desiccation resistance,
      the population rankings are: Darwin Melbourne > Townsville > Brisbane Melville I.
      and for development time, rankings are similar: Darwin Melbourne < Townsville <
      Brisbane Melville I.Therefore resource utilization heterogeneity is greatest in
      populations not greatly stressed by desiccation and where development times are
      extended. In total therefore, the utilization of a diversity of resources is a
      feature of populations tending somewhat towards a K-strategy; this is emphasized
      by the relative heterogeneity among isofemale strains of these populations for
      desiccation resistance and to a lesser extent development times.The D.
      melanogaster gene pool can be viewed as made up of climate-associated races.
      Since the ethanol tolerances of adjacent (and climatically similar) Darwin and
      Melville I. are very different, resource utilization races may occur within
      climatic races. Such a mosaic of resource utilization races are more likely in
      climatically extreme than in optimal habitats. 

PMID- 24301147
TI  - Mate selection by selection index theory.
AB  - Mate selection by selection index prediction of total merit in expected progeny
      is proposed as a rational basis for making recommendations in the choice of a
      bull to which a cow may be mated. Growth in USA of service programs recommending
      bulls to particular cows has motivated the need to rationalize mate selection
      processes. This paper illustrates that mate selection on the basis of highest
      index value for expected progeny among potential mates can justify special mate
      selection programs, when a nonlinear relationship exists between at least one
      trait in the index and merit. 

PMID- 24301148
TI  - Chromosome and isoenzyme studies on cells derived from protoplast fusion of
      Nicotiana glauca with glycine max-Nicotiana glauca cell hybrids.
AB  - The somatic hybrids of Glycine max (L)Merr.-Nicotiana glauca Grah. exhibited a
      preferential loss of N. glauca chromosomes. When protoplasts from such hybrid
      cells were 'back fused' twice to N. glauca protoplasts, a considerable increase
      in stability of the N. glauca chromosomes was observed. Gel electrophoresis
      studies of aspartate aminotransferase showed that the chromosome(s) responsible
      for this enzyme was stabilized in the 'back fused' hybrid cell lines. The data
      suggest that the 'back fusion' technique described in this study might aid in
      stabilizing somatic hybrids. 

PMID- 24301149
TI  - Selection for egg production on part records : Part 1: Evaluation of short term
      response to selection.
AB  - Responses from four generations of index selection for egg production to 280 days
      of age in four White Leghorn populations have been presented. A pedigreed
      randombred population derived from one of the lines was reared with the selected
      lines to measure the environmental trend. The magnitude of total as well as
      average response although varying from population to population was positive in
      all the lines studied. Close correspondence between predicted and realized gains
      indicated that natural selection, genotype environmental interactions and
      environmental fluctuations were unimportant during the course of selection.
      Realized heritabilities agreed fairly well with the estimated heritabilities in
      at least three out of four populations studied. Probable reasons for variable and
      insufficient response were investigated. 

PMID- 24301150
TI  - Effects of two growth retardants on tissue permeability in Pisum sativum and Beta
      vulgaris.
AB  - The effects of growth retardants, 4-hydroxy-5-isopropyl-2
      methylphenyltrimethylammonium chloride-1-piperidine carboxylate (AMO-1618 or AMO)
      and 2-chloroethyltrimethylammonium chloride (CCC), applied with and without
      gibberellic acid (GA3), on beta-[(3)H]alanine uptake and leakage from pea (Pisum
      sativum L.) and betacyanin efflux from beetroot (Beta vulgaris L.) tissue were
      examined. Both compounds decreased the amount of beta-[(3)H]alanine taken up into
      pea leaf discs, and increased the quantity of radioactive label that subsequently
      leaked out of this tissue. Efflux of betacyanin from slices of beetroot was also
      found to be promoted by treatment with CCC or AMO-1618. In no case were these
      effects reversed by application of GA3. It is concluded that the growth
      retardants may be altering tissue permeability by an interaction with the cell
      membranes, and this may account for some of the side effects of the retardants
      which cannot be explained on the basis of their inhibiting action on gibberellin
      synthesis. 

PMID- 24301151
TI  - Photomodulation of growth and specific changes in fatty acid amounts in
      internodes of green Vigna sinensis L.
AB  - First internode growth of green Vigna sinensis L. can be widely modified by light
      or dark treatments. In all the treatments used there is a good correlation
      between the internode growth and the rate of C18-1 accumulation. None of the
      other fatty acids show such a correlation. 

PMID- 24301152
TI  - Localisation and characterisation of homoserine dehydrogenase isolated from
      barley and pea leaves.
AB  - Two forms of homoserine dehydrogenase exist in the leaves of both barley and pea;
      one has a large molecular weight and is inhibited by threonine, the other is of
      smaller molecular weight and insensitive to threonine but inhibited by cysteine.
      The subcellular localisation of these enzymes has been examined. Both plants have
      60-65% of the total homoserine dehydrogenase activity present in the chloroplast
      and this activity is inhibited by threonine. The low molecular weight, threonine
      insensitive form is present in the cytoplasm. Total homoserine dehydrogenase
      activity from barley leaves showed progressive desensitisation towards threonine
      with age in a similar manner to that previously described for maize. It was shown
      that the effect was due to desensitisation of the chloroplast enzyme, and not to
      an increase in the insensitive cytoplasm enzyme. No corresponding desensitisation
      to threonine was detected in pea leaves. The different forms of homoserine
      dehydrogenase could be separated from pea leaves by chromatography on Blue
      Sepharose; the threonine-sensitive enzyme passed straight through and the
      threonine insensitive form was bound. A similar separation of the barley leaf
      isoenzymes was obtained using Matrex Gel Red A affinity columns; in this case
      however, the threonine-sensitive isoenzyme was bound. In both plants, the
      threonine insensitive isoenzyme was subject to greater inhibition by cysteine
      than was the threonine-sensitive isoenzyme. 

PMID- 24301153
TI  - Effects of temperature, oxygen concentration, leaf age and seasonal variations on
      the CO2 compensation point of Lolium perenne L. : Comparison with a mathematical
      model including non-photorespiratory CO2 production in the light.
AB  - Various factors affect the CO2 compensation point of detached leaves of Lolium
      perenne L. These include oxygen concentration, temperature, leaf age, and season
      (spring and summer). Analysis of the results using the model of G.D. Farquhar, S.
      von Caemmerer and J.A. Berry (1980) Planta 149, 78-90, indicates that some of the
      CO2 evolved by leaves in the light is derived from sources other than
      photorespiration. It is suggested that the operation of the tricarboxylic acid in
      the light can account for most of this CO2. 

PMID- 24301154
TI  - Stereospecificity and electrogenicity of amino acid transport in Riccia fluitans.
AB  - In the aquatic liverwort Riccia fluitans, membrane depolarization (DeltaPsim),
      change in membrane conductance (Deltagm), and current-voltage (I-V)
      characteristics in the presence of different amino acids as well as the uptake of
      (14)C-labeled amino acids were measured. L-isomers of the tested amino acids
      generate larger electrical effects (DeltaPsim, Deltagm) than D-isomers, and the I
      V characteristics show that the positive electrical inward-current of 20 mA m(-2)
      generated by 0.5 mM D-serine is only about 50% of the current generated by adding
      0.5 mM L-serine. Whereas alpha- and beta-amino acids rapidly depolarize the
      membrane to the same extend, with gamma-aminobutyric acid (gamma-AB) and
      dipeptides no significant electrical effects have been measured. The uptake
      kinetics of (14)C-labeled amino acids display three components: (I) A saturable
      high-affinity component with Ks-values of 48 MUM D-alanine, 12 MUM alpha
      aminoisobutyric acid (AIB), 9 MUM L-alanine, 8 MUM L-proline, and 6 MUM L-serine,
      respectively; (2) an apparently linear low-affinity component, and (3) an also
      linear but unspecific component at concentrations >20 times the given Ks-value.
      Uptake of (14)C-labeled AIB can be inhibited competitively by all tested neutral
      amino acids, the L-isomers being more effective than the D-isomers, as well as by
      ammonium or methylamine. Vice versa, AIB competitively inhibits uptake of L
      serine and L-alanine. It is concluded that an uncharged stereospecific carrier
      for the investigated amino acids exists in the plasmalemma of Riccia fluitans.
      Accumulation ratios of about 50 suggest secondary active transport driven by a
      transmembrane electro-chemical gradient (mainly DeltaPsim) which is generated by
      the electrogenic proton pump. It is suggested that this carrier binds to the
      amino group forming either a charged binary complex with positively charged
      amines (Felle 1980), or an uncharged complex with gamma-AB or dipeptides, whereas
      electrogenic transport of alpha- and beta-amino acids is mediated by a ternary
      carrier complex, probably charged by a proton. 

PMID- 24301155
TI  - A light-dependent current associated with chloroplast aggregation in the alga
      Vaucheria sessilis.
AB  - Local irradiation of the alga Vaucheria sessilis (Vauch.) D.C. with blue light,
      which stimulates cortical fiber reticulation and chloroplast aggregation (M.R.
      Blatt and W.R. Briggs, 1980, Planta 147, 355-362), also induces an outward
      directed current from the irradiated region of the cell. This current appears in
      conjunction with cortical fiber reticulation and precedes chloroplast
      aggregation. The current is not photosynthetic in origin, as indicated by
      experiments with 3(3,4-dichlorophenyl)-1,1-dimethyl urea and carbonyl-cyanide-m
      chlorophenylhydrazone (CCCP). It shows a wavelength-dependence similar to that of
      chloroplast aggregation and reaches a maximum of 500 nA cm(-2) with saturating
      light intensities. The current is not dependent upon the presence of Na(+), K(+),
      or Cl(-) in a test medium containing only Na(+), K(+), Ca(2+), and Cl(-), but is
      inhibited, apparently nonspecifically, in the absence of external calcium. Both
      the light-induced current and chloroplast aggregation are stimulated by increases
      in the external KCl concentration and are inhibited by sub-micromolar
      concentrations of CCCP or by external pHs below approximately 5.5. We suggest
      that blue light stimulates the local extrusion of cations, possibly of protons,
      at the plasma membrane, an event which may act to destabilize the cortical fibers
      in Vaucheria, disrupt cytoplasmic streaming, and eventually lead to organelle
      aggregation in the light. 

PMID- 24301156
TI  - Evidence for amino-acid: proton cotransport in Ricinus cotyledons.
AB  - During germination and early growth of the castor-bean (Ricinus communis L.),
      protein in the endosperm is hydrolyzed and the amino acids are transferred into
      the cotyledons and then via the translocation stream to the axis of the growing
      seedling. The cotyledons retain the ability to absorb amino acids after removal
      of the endosperm and hypocotyl, exhibiting rates of transport up to 70 MUmol g(
      1) h(-1). The transport of L-glutamine was not altered by KCl or NaCl in low
      concentrations (0-20 mM). High concentrations of KCl (100 mM) inhibited
      transport, presumably by decreasing the membrane potential. An increase in the pH
      of the medium bathing the cotyledons was observed for 10 min following addition
      of L-glutamine but not with D-glutamine, which is not transported. The rate of
      proton uptake was dependent on the concentration of L-glutamine in the external
      solution. Inhibitors and uncouplers of respiration (azide, 2, 4-dinitrophenol,
      carbonyl cyanide phenylhydrazone and N-ethylmaleimide) inhibited both L-glutamine
      uptake and L-glutamine-induced proton uptake. Amino acids other than L-glutamine
      also caused a transient pH rise and the rate of proton uptake was proportional to
      the rate of amino-acid uptake. The stoichiometry was 0.3 protons per amino acid
      transported. Addition of sucrose also caused proton uptake but the alkalisation
      by sucrose and by amino acids were not additive. Nevertheless, when sucrose was
      added 60 min after providing L-glutamine at levels saturating its uptake system,
      a rise in pH was again observed. The results were consistent with amino-acid
      transport and sucrose transport in castor-bean cotyledons both occurring by a
      proton cotransport in the same membrane system but involving separate carriers. 

PMID- 24301157
TI  - Leghaemoglobin within bacteroid-enclosing membrane envelopes from soybean root
      nodules.
AB  - Methods are reported for the preparation from soybean (Glycine max (L.) Merr.)
      root nodules, of well-washed, intact membrane envelopes containing bacteroids.
      The intact envelopes are of much lower density than the bacteroids within and
      therefore only low speed centrifugation (approx. 150 g) may be used. The optimum
      osmotic strength is 600 mOsm/kg H2O. The envelope contents were recovered
      following mild osmotic shock and-or hard centrifugal packing at >10,000 g.
      Extracts prepared in this way contained leghaemoglobin (identified
      spectrophotometrically), low-molecular-weight fluorescent materials and other
      components which are yet to be identified. Envelope leghaemoglobin did not react
      with specific antibody until the envelopes were ruptured. (131)I-Labelled
      leghaemoglobin or bovine serum albumin, added during initial breakage of nodule
      cells, was not released when envelopes were ruptured to release leghaemoglobin.
      It is therefore concluded that this leghaemoglobin is located within the envelope
      space and did not arise from adhering or occluded cytosol leghaemoglobin. Based
      on the number and dimensions of microscopically intact envelopes in these
      preparations, the concentration within that space was in the range 178-523 MUM.
      Based on these estimates, leghaemoglobin within envelopes represented about one
      third of the total amount present in the nodule cells. Flat-bed isoelectric
      focusing of partially-purified envelope leghaemoglobin demonstrated that the
      latter contained all of the leghaemoglobin components previously reported for
      soybean nodules and an additional minor component focusing between
      leghaemoglobins a and b. 

PMID- 24301158
TI  - (15)N 2 Incorporation and metabolism in the lichen Peltigera aphthosa Willd.
AB  - The Nostoc in the cephalodia of the lichen Peltigera aphthosa Willd. fixed (15)N2
      and the bulk of the nitrogen fixed was continuously transferred from it to its
      eukaryotic partners (a fungus and a green alga, Coccomyxa sp.). Kinetic studies
      carried out over the first 30 min, after exposure of isolated cephalodia to
      (15)N2, showed that highest initial (15)N2-labelling was into NH 4 (+) . After 12
      min little further increase in the NH 4 (+) label occurred while that in the
      amide group of glutamine and in glutamate continued to increase. The (15)N
      labelling of the amino group of glutamine and of aspartate increased more slowly,
      followed by an increase in the labelling of alanine. When total incorporation of
      (15)N-label was calculated, the overall pattern was found to be rather similar
      except that, throughout the experiment, the total (15)N incorporated into
      glutamate was about six times greater than that into the amide group of
      glutamine. Pulse chase experiments, in which (14)N2 was added to cephalodia
      previously exposed to (15)N2, showed that the NH 4 (+) pool rapidly became
      depleted of (15)N-label, followed by decreases in the labelling of glutamate, the
      amide group of glutamine and aspartate. The (15)N-labelling of alanine, however,
      continued to increase for a period. When isolated cephalodia were treated with L
      methionine-SR-sulphoximine, an inhibitor of glutamine synthetase (EC 6.3.1.2),
      and azaserine, an inhibitor of glutamate synthase (EC 2.6.1.53), there was no
      detectable labelling in glutamine although the (15)N-labelling of glutamate
      increased unimpaired. On treating the cephalodia with amino-oxyacetate, an
      inhibitor of aminotransferase activity, the alanine pool decreased. Evidence was
      obtained that glutamine synthetase and glutamate synthase were located in the
      Nostoc, and that glutamate dehydrogenase (EC 1.4.1.4) and various amino
      transferases were located in the cephalodial fungus. Possible implications of
      these findings are discussed. 

PMID- 24301159
TI  - Chloroplast translocations induced by light pulses : Effects of single light
      pulses.
AB  - The effect of single blue-light pulses on chloroplast rearrangement was studied
      in the leaves of Tradescantia albiflora, Chlorophytum elatum, and Lemna trisulca.
      For measuring translocations in terrestrial plants the method of transmission
      changes was used; translocations in the water plant Lemna were studied by direct
      microscopic observation and counting. Strong light (30 W m(-2)) applied in the
      form of short pulses, shorter than a lag period of translocations, induces some
      transient effects in the following dark period. With short pulses, transient
      rearrangements of chloroplasts to a weak-light position were found. With longer
      pulse duration, biphasic responses took place in Tradescantia and Lemna: The
      initial movement to a partial strong-light position was followed by a wave of
      translocation to a weak-light arrangement. In Chlorophytum this type of response
      appeared only in a narrow fluence range. The validity of the reciprocity law in
      relation to fluence rate and time of irradiation was confirmed for Tradescantia.
      The results may give us an insight into the kinetics of the primary effects of
      light in the translocation process. 

PMID- 24301160
TI  - Effect of abscisic acid on the transport of assimilates in barley.
AB  - The effect of abscisic acid (ABA) on assimilate transport in barley was
      investigated in two parallel experiments. First, the effect upon [(14)C]sucrose
      transport from the flag leaf to the ear of a single ABA application made at
      different stages of growth of the fruits was investigated; the effect was
      measured 24 h after treatment. Second, the effect of a single application of ABA
      made at the same stages of growth as above on grain weight of the mature plant
      was investigated. In both types of experiments ABA was applied once to the ear of
      different plants as an aqueous solution (10(-3)-10(-5) M), one to five weeks
      after anthesis. [(14)C] sucrose was applied by means of agar blocks. Parallel to
      these experiments, the endogenous content of ABA was investigated in the
      developing grains. When ears were treated with ABA two or four weeks after
      anthesis, an increase of up to 70% in the (14)C-transport from the flag leaf to
      the ear was observed within a 24-h period after treatment (short duration
      experiments). At these growth stages the endogenous concentrations of ABA were
      low. In sharp contrast, ABA, especially in a concentration of 10(-3) M, decreased
      (14)C-import from the flag leaf when applied three weeks after anthesis. At this
      stage the endogenous ABA content had reached its maximum. Long duration
      experiments with a single application of ABA to the car two weeks after anthesis
      resulted in a marked increase of weight per thousand kernels. ABA applications
      made earlier or later than two weeks after anthesis either reduced the grain
      weight or had no effect. It is concluded that ABA is involved in the regulation
      of assimilate transport from the leaves to the grains, possibly by influencing
      the unloading of sieve tubes in the ears. Promotion or inhibition of assimilate
      import by exogenously applied ABA may depend on the developmental stage of the
      grains and on the endogenous ABA level. 

PMID- 24301161
TI  - In vitro biosynthesis of the C-glycosidic bond in aloin.
AB  - Biosynthetic studies with cell-free extracts from Aloe arborescens Mill.
      demonstrate the transfer of the glucose moiety from UDP-glucose to aloe emodin
      anthrone, forming the C-glycosidic linkage in the anthracene derivative aloin.
      The pH-dependence and the specificity of UDP-glucose and aloe emodin anthrone for
      the biosynthesis of the C-glycosidic bond in aloin are shown. 

PMID- 24301162
TI  - Effects of environmental conditions on isoprene emission from live oak.
AB  - Live-oak plants (Quercus virginiana Mill.) were subjected to various levels of
      CO2, water stress or photosynthetic photon flux density to test the hypothesis
      that isoprene biosynthesis occurred only under conditions of restricted CO2
      availability. Isoprene emission increases as the ambient CO2 concentration
      decreased, independent of the amount of time that plants had photosynthesized at
      ambient CO2 levels. When plants were water-stressed over a 4-d period
      photosynthesis and leaf conductance decreased 98 and 94%, respectively, while
      isoprene emissions remained constant. Significant isoprene emissions occurred
      when plants were saturated with CO2, i.e., below the light compensation level for
      net photosynthesis (100 MUmol m(-2) s(-1)). Isoprene emission rates increased
      with photosynthetic photon flux density and at 25 and 50 MUmol m(-2) s(-1) were 7
      and 18 times greater than emissions in the dark. These data indicate that
      isoprene is a normal plant metabolite and not - as has been suggested - formed
      exclusively in response to restricted CO2 or various stresses. 

PMID- 24301163
TI  - Dihydroconiferyl alcohol - A cell division factor from Acer species.
AB  - A compound that stimulated growth of soybean callus was isolated from spring sap
      of sycamore (Acer pseudoplatanus L.). Insufficient compound was isolated to
      permit it to be characterised. A compound with identical properties was isolated
      from commercial maple syrup, the concentrated spring sap of Acer saccharum L. The
      compound was identified as 3-(3-methoxy-4-hydroxyphenyl)-propan-1-ol
      (dihydroconiferyl alcohol, DCA). DCA was also active in the tobacco callus and
      radish leaf senescence assays, but was inactive in four other tests for cytokinin
      activity. DCA acted synergistically with kinetin to promote soybean callus
      growth. It is concluded that DCA has properties distinct from those of purine
      cytokinins. 

PMID- 24301164
TI  - Immunohistochemical localization of beta-glucosidases in lignin and isoflavone
      metabolism in Cicer arietinum L. seedlings.
AB  - Coniferin specific- and isoflavone 7-glucoside specific beta-glucosidases have
      been localized in stem and root sections of chick pea (Cicer arietinum L.)
      seedlings by the indirect immunofluorometrical method. The coniferin specific
      beta-glucosidase has been found in the cell walls of the tracheary elements and
      of the endo-, epi-, and exodermis. All these tissues are known to contain either
      lignin or polymers, like suberin and cutin, which consist partially of
      phenylpropanoid elements. The localization of this beta-glucosidase is therefore
      in agreement with its postulated relationship to the phenylpropanoid metabolism.
      The isoflavone 7-glucoside specific beta-glucosidase, on the other hand, is
      predominantly located in the parenchymatic cortex cells, and obviously in the
      cytoplasm. These cells are known to contain the isoflavone formononetin, which
      has been shown to undergo turnover in chick pea seedlings. We therefore have good
      reason to assume that this beta-glucosidase is involved in the metabolism of the
      7-glucoside of this isoflavone. 

PMID- 24301165
TI  - Glutamine synthetase of Chlamydomonas: Rapid reversible deactivation.
AB  - A 70% reduction in glutamine synthetase (GS) activity was observed within 5 min
      when 5 mM NH3 and darkness was applied to steady-state cells of Chlamydomonas
      utilising NO3. The enzyme was reactivated in vivo by reillumination of the
      culture and in vitro by treatment with thiol reagents. The activity modulations
      affected the synthetase and transferase activities similarly and were not
      influenced by protein synthesis inhibitors. Deactivation of GS was also observed
      when steady-state cells were treated with an uncoupler of phosphorylation,
      carbonylcyanide m-chlorophenylhydrazone (CCCP) or inhibitors of the electron
      transport chain but under these conditions the activity modulation affected over
      90% of the activity and was irreversible. The mechanism of the physiological
      deactivation of GS is discussed in relation to both the in vivo and in vitro
      findings. 

PMID- 24301166
TI  - A descriptive definition of primary prevention.
AB  - This theoretical paper links prevention activities and wellness activities in a
      context of social action. It attempts to define prevention by describing the
      essential characteristics of the prevention process. Six characteristics are
      identified: proactive, generic, developmental, experiential, systemic, and
      collaborative. A number of prevention programs which appear to illustrate one or
      more of these characteristics are cited. The need for such a process as an
      approach to many contemporary individual and social problems is assumed. The
      author's intention is to provide program planners and funders with a usable
      theoretical base for developing and evaluating specific programs. 

PMID- 24301167
TI  - Relationships between family background problems and social problem solving
      skills of young normal children.
AB  - Relationships between family background problems and social problem solving (SPS)
      skills were studied in normal third grade children. Twelve urban and suburban
      classroom teachers provided information about the presence of six family
      background problems for 243 children. Three problem solving skills were assessed:
      1) alternative solution thinking, means-end thinking, and 3) social role taking.
      Overall, children with, one or more family problems, compared to those with no
      problems, generated fewer effective solutions and were less able to carry out a
      stepwise plan or to take the point of view of another. Differential reltionships
      were found between specific family background problems and specific problem
      solving skill deficiencies. Implications of the findings for school-based
      preventive programming were considered. 

PMID- 24301168
TI  - Student attitudinal inventory for outcome evaluation of adolescent drug abuse
      prevention programs.
AB  - This study introduces an evaluation instrument entitled the "High-Risk Student
      Attitudinal Inventory." It can be used for outcome evaluation in assessing the
      effectiveness of various primary prevention programs aimed at deterring
      adolescent drug abuse. This instrument has seven attitudinal syndromes that are
      theoretically based and are empirically related to student drug involvement. Each
      attitudinal syndrome is composed of ten Likert-type scale items. The mean
      Cronbach Alpha coefficient of reliability pertaining to the scales is .83.
      Criterion-related validity of the scales is established through a known-group
      method. The groups identified are the current drug users and non-drug users. 

PMID- 24301169
TI  - An evaluation system for school-community prevention programs.
AB  - A management-oriented system for the evaluation of school-community prevention
      programs is described and examples of how the system has been applied to serve
      program management decisions with primary, secondary, and tertiary prevention
      programs are provided. The approach, termed "Program Analysis and Review System
      (PARS)," emphasizes a cooperative relationship between a program evaluator and
      prevention program manager in order that informed judgments can be made about
      program development and improvement. PARS, which was developed by the author in
      response to a perceived need for management-oriented approaches to prevention
      program evaluation, has been field tested with school-community prevention
      programs in Bergenfield, New Jersey, and Somerville, New Jersey, and has been
      adapted for use in other communities. PARS consists of three interrelated steps:
      Program Specification, Program Documentation, and Program Outcome Determination. 

PMID- 24301170
TI  - Prevention is a purple puppet ... a playful panda ... a personalized placard.

PMID- 24301171
TI  - A national consortium on psychological aspects of social change & community
      development: An idea whose time has come.

PMID- 24301172
TI  - Primary prevention program clearinghouse psychology department-Dewey hall
      university of Vermont, Burlington, VT. 05405.

PMID- 24301173
TI  - Postcollisional mafic igneous rocks record crust-mantle interaction during
      continental deep subduction.
AB  - Findings of coesite and microdiamond in metamorphic rocks of supracrustal
      protolith led to the recognition of continental subduction to mantle depths. The
      crust-mantle interaction is expected to take place during subduction of the
      continental crust beneath the subcontinental lithospheric mantle wedge. This is
      recorded by postcollisional mafic igneous rocks in the Dabie-Sulu orogenic belt
      and its adjacent continental margin in the North China Block. These rocks exhibit
      the geochemical inheritance of whole-rock trace elements and Sr-Nd-Pb isotopes as
      well as zircon U-Pb ages and Hf-O isotopes from felsic melts derived from the
      subducted continental crust. Reaction of such melts with the overlying wedge
      peridotite would transfer the crustal signatures to the mantle sources for
      postcollisional mafic magmatism. Therefore, postcollisonal mafic igneous rocks
      above continental subduction zones are an analog to arc volcanics above oceanic
      subduction zones, providing an additional laboratory for the study of crust
      mantle interaction at convergent plate margins. 

PMID- 24301174
TI  - The study of maturational timing effects in adolescence.

PMID- 24301175
TI  - Measuring physical status and timing in early adolescence: A developmental
      perspective.
AB  - Recently, the timing-of-events model typically used for exploring adult
      development has been proposed for studying early adolescence and the pubertal
      processes occurring then. As a consequence, new interest has been generated about
      the psychological effects of being early, on time, or late in sexual maturation
      during early adolescence. A major issue has to do with the choice of maturational
      events to study, since puberty is a process involving numerous events, all of
      which have a different developmental course. This paper reviews some of the
      maturational events that are applicable in studying psychological effects of
      pubertal status and timing. Nine changes are reviewed (bone, height, weight, body
      fat, breast, body hair, penile, testicular, and menarcheal changes) in terms of
      measurement techniques, psychometric properties, and intercorrelations with other
      pubertal events. In addition, the usefulness of each measure for psychological
      research on maturational timing and status is discussed. Finally, how pubertal
      measures may be incorporated into a developmental perspective is considered,
      especially with regard to rate, duration, and asynchrony of pubertal changes. 

PMID- 24301176
TI  - Pubertal timing and grade effects on adjustment.
AB  - Effects on adjustment of biological maturation and social timing were compared
      using data from a longitudinal sample of 335 young adolescents, who were followed
      from the sixth through eighth grades. Biological maturation was estimated from
      the relative timing of the adolescent growth spurt. Social timing was assessed by
      grade in school. Five adjustment constructs were examined: school achievement
      (course grades in five subjects), family relations (a 17-item scale), peer
      relations (a 10-item scale), body image (an 11-item scale), impulse control (an 8
      item scale), and psychopathology (an 11-item emotional tone scale and an 11-item
      general psychopathology scale). All but one adjustment construct showed grade
      effects, but only three of the six constructs showed pubertal timing effects.
      There were no grade by pubertal timing effects. Although there were gender
      differences for some of the adjustment constructs, there were no gender by
      pubertal timing effects. The results are discussed in terms of the life-span
      developmental perspective. 

PMID- 24301177
TI  - Satisfaction with body image for early adolescent females: The impact of pubertal
      timing within different school environments.
AB  - During adolescence dramatic physical changes take place which the individual must
      incorporate into his or her evolving body image. The impact of different school
      environments on this incorporation process is explored using data on 225 White
      females from a longitudinal study. Differences in physical characteristics
      between early, middle, and late developers were assessed each year. The effects
      of pubertal timing on satisfaction with body image dimensions and self-esteem
      were then explored for sixth- and seventh-graders within different school
      environments. Reference group theory was used to examine three alternative
      hypotheses. Early versus late onset of menarche had different effects on certain
      aspects of satisfaction with body image, depending on the school environment.
      Results support the strength of the cultural ideal of thinness for women, but no
      other hypothesis had consistent support. The findings indicated the need to
      consider a multiplicity of factors in relation to specific body image dimensions.

PMID- 24301178
TI  - The effects of pubertal timing on body image, school behavior, and deviance.
AB  - Variation in the timing of pubertal maturation may result in behavioral
      differences among early, mid-, and late maturers. Using data from the National
      Health Examination Survey, a national probability sample of children and youth
      aged 12-17, we investigated the relationships between maturational timing and
      body image, school behavior, and deviance. In terms of body image, the early
      maturing boys were the group most satisfied with height and weight. The early
      maturing girls were most dissatisfied with weight, with 69% wishing to be
      thinner. This great dissatisfaction with weight reported by early maturing girls
      is probably not an affect of early maturation, but a concomitant of maturation in
      general. The majority of girls became dissatisfied with their weight as they
      matured, and females from the higher social groups were more likely to want to be
      thinner than females from lower groups. Thus, a normal developmental process is
      being viewed negatively by females and positively by males. Male early maturers
      more often had deviant behavior, but there were no consistent findings for girls.
      There was no effect of maturational timing on teacher reports of school absence,
      adjustment, popularity, need for discipline, or grade repetition. 

PMID- 24301179
TI  - The relation of relative hormonal levels and physical development and social
      emotional behavior in young adolescents.
AB  - The study examined the relation between timing of physical maturation and
      problems of adjustment and peer relations. The participants were 9-14-year-old
      boys (N=56) and girls (N=52). Assessments of physical maturation consisted of
      pubertal staging according to Tanner criteria and serum determinations of
      luteinizing hormone, follicle stimulating hormone, testosterone, estradiol,
      dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione.
      There was approximately an equal number of boys and girls in each pubertal stage.
      The psychological measures were the Psychopathology and Emotional Tone subscales
      from the Offer Self-Image Questionnaire for Adolescents and interview questions
      to assess interactions with peers. Psychopathology and emotional tone (sad
      effect) scores were higher for boys with high-for-age adrenal androgens and lower
      for boys with high-for-age sex steroids. Behavioral manifestations of sexuality,
      interest in dating, was higher for boys with high-for-age adrenal androgens.
      Dating and spending time with friends were higher for boys with high-for-age
      gonadotropins. Psychopathology and emotional tone were higher for girls with high
      for-age gonadotropins. The results indicate that high-for-age hormone level or
      early timing of puberty generally was related to adverse psychological
      consequences for boys and girls, with relations being stronger for boys than for
      girls. 

PMID- 24301181
TI  - Feasibility of integrating a multi-camera optical tracking system in intra
      operative electron radiation therapy scenarios.
AB  - Intra-operative electron radiation therapy (IOERT) combines surgery and ionizing
      radiation applied directly to an exposed unresected tumour mass or to a post
      resection tumour bed. The radiation is collimated and conducted by a specific
      applicator docked to the linear accelerator. The dose distribution in tissues to
      be irradiated and in organs at risk can be planned through a pre-operative
      computed tomography (CT) study. However, surgical retraction of structures and
      resection of a tumour affecting normal tissues significantly modify the patient's
      geometry. Therefore, the treatment parameters (applicator dimension, pose
      (position and orientation), bevel angle, and beam energy) may require the
      original IOERT treatment plan to be modified depending on the actual surgical
      scenario. We propose the use of a multi-camera optical tracking system to
      reliably record the actual pose of the IOERT applicator in relation to the
      patient's anatomy in an environment prone to occlusion problems. This information
      can be integrated in the radio-surgical treatment planning system in order to
      generate a real-time accurate description of the IOERT scenario. We assessed the
      accuracy of the applicator pose by performing a phantom-based study that
      resembled three real clinical IOERT scenarios. The error obtained (2 mm) was
      below the acceptance threshold for external radiotherapy practice, thus
      encouraging future implementation of this approach in real clinical IOERT
      scenarios.

PMID- 24301180
TI  - The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans.
AB  - Neuropeptides have central roles in the regulation of homoeostatic behaviours
      such as sleep and feeding. Caenorhabditis elegans displays sleep-like quiescence
      of locomotion and feeding during a larval transition stage called lethargus and
      feeds during active larval and adult stages. Here we show that the neuropeptide
      NLP-22 is a regulator of Caenorhabditis elegans sleep-like quiescence observed
      during lethargus. nlp-22 shows cyclical mRNA expression in synchrony with
      lethargus; it is regulated by LIN-42, an orthologue of the core circadian protein
      PERIOD; and it is expressed solely in the two RIA interneurons. nlp-22 and the
      RIA interneurons are required for normal lethargus quiescence, and forced
      expression of nlp-22 during active stages causes anachronistic locomotion and
      feeding quiescence. Optogenetic stimulation of the RIA interneurons has a
      movement-promoting effect, demonstrating functional complexity in a single-neuron
      type. Our work defines a quiescence-regulating role for NLP-22 and expands our
      knowledge of the neural circuitry controlling Caenorhabditis elegans behavioural
      quiescence. 

PMID- 24301182
TI  - The apicoplast genome of Leucocytozoon caulleryi, a pathogenic apicomplexan
      parasite of the chicken.
AB  - Leucocytozoon caulleryi, a haemosporidian parasite of the chicken (Gallus gallus
      domesticus), can be highly pathogenic and often fatal. Although this parasite is
      extremely relevant to veterinary science, knowledge of its genomic features is
      limited. To gain information applicable to developing novel control methods for
      the parasite, we analyzed the apicoplast genome of L. caulleryi. This
      extranuclear organellar DNA of 85.1% A + T and a unit of 34,779 bp was found to
      encode almost the same set of genes as the plastid genome of Plasmodium
      falciparum, including 16 tRNA and 30 protein coding genes, and except for one
      open reading frame, ORF91 absent in L. caulleryi. As in P. falciparum, the L.
      caulleryi apicoplast DNA contains two sets of a unique inverted repeat (IR), each
      one 5,253 bp and encoding genes specifying one large and one small rRNA subunit
      and nine tRNAs but no protein, and separated by a unique 13 bp sequence. Studies
      of several haemosporidian apicoplast DNA sequences have identified a
      corresponding IR region; however, none of these studies has looked at the
      complete sequence, even for well-studied species such as P. falciparum.
      Phylogenetic studies using a concatenated amino acid sequence based on the open
      reading frames confirmed the close relationship between L. caulleryi and
      Plasmodium spp. In this study, we determined the nucleotide sequence of the
      entire L. caulleryi apicoplast genome, including the region connecting the two IR
      units. This is the first report of the complete nucleotide sequence of a
      haemosporidian apicoplast DNA with a canonical IR.

PMID- 24301184
TI  - Synthesis and antibacterial activity of tripropeptin C derivatives modified at
      the carboxyl groups.

PMID- 24301183
TI  - Computational identification and analysis of orphan assembly-line polyketide
      synthases.
AB  - The increasing availability of DNA sequence data offers an opportunity for
      identifying new assembly-line polyketide synthases (PKSs) that produce
      biologically active natural products. We developed an automated method to extract
      and consolidate all multimodular PKS sequences (including hybrid PKS/non
      ribosomal peptide synthetases) in the National Center for Biotechnology
      Information (NCBI) database, generating a non-redundant catalog of 885 distinct
      assembly-line PKSs, the majority of which were orphans associated with no known
      polyketide product. Two in silico experiments highlight the value of this search
      method and resulting catalog. First, we identified an orphan that could be
      engineered to produce an analog of albocycline, an interesting antibiotic whose
      gene cluster has not yet been sequenced. Second, we identified and analyzed a
      hitherto overlooked family of metazoan multimodular PKSs, including one from
      Caenorhabditis elegans. We also developed a comparative analysis method that
      identified sequence relationships among known and orphan PKSs. As expected, PKS
      sequences clustered according to structural similarities between their polyketide
      products. The utility of this method was illustrated by highlighting an
      interesting orphan from the genus Burkholderia that has no close relatives. Our
      search method and catalog provide a community resource for the discovery of new
      families of assembly-line PKSs and their antibiotic products. 

PMID- 24301185
TI  - Pedopeptins, novel inhibitors of LPS: taxonomy of producing organism,
      fermentation, isolation, physicochemical properties and structural elucidation.
AB  - In the course of our screening for inhibitors of lipopolysaccharide (LPS) binding
      to cellular receptor CD14, potent inhibitory activity was detected in the
      cultured broth of Pedobacter sp. SANK 72003. Three active compounds, pedopeptin
      A, B and C, were isolated from the broth and their structures were elucidated by
      physicochemical and spectral data to be new cyclic depsipeptides. 

PMID- 24301186
TI  - 13th International Conference on the Chemistry of Antibiotics and Other Bioactive
      Compounds (ICCA-13).

PMID- 24301187
TI  - Synthesis, crystal structure and lithium ion conduction of Li3BP2O8.
AB  - Single crystals of Li3BP2O8 were prepared by heating a mixture of starting
      materials with a Li : B : P molar ratio of 22 : 11 : 13 at 933 K in air and by
      cooling at a rate of -10 K h(-1). The X-ray diffraction (XRD) reflections of a
      single crystal were indexed with triclinic cell parameters: a = 5.1888(5) A, b =
      7.4118(7) A, c = 7.6735(7) A, alpha = 101.18(1) degrees , beta = 105.07(1)
      degrees , gamma = 90.34(1) degrees  (space group P1 (no. 2)). In the crystal
      structure of Li3BP2O8, BO4 and PO4 tetrahedra share O atoms and form one
      dimensional 1(infinity)[BP2O8](3-) chains along the c-axis direction. A
      polycrystalline Li3BP2O8 bulk sample was synthesized by the solid state reaction
      of Li4P2O7 and LiPO3 prepared from the starting materials in advance with H3BO3
      at 923 K. The lithium ion conductivities measured for the polycrystalline sample
      by the AC impedance and DC methods were 1.5 * 10(-5) S cm(-1) at 583 K and 6.0 *
      10(-8) S cm(-1) at 423 K, respectively.

PMID- 24301188
TI  - Probing 27Al-13C proximities in metal-organic frameworks using dynamic nuclear
      polarization enhanced NMR spectroscopy.
AB  - We show how (27)Al-(13)C proximities in the microporous metal-organic framework
      MIL-100(Al) can be probed using advanced (27)Al-(13)C NMR methods boosted by
      Dynamic Nuclear Polarization. 

PMID- 24301189
TI  - Feasibility of accessing data in hospitalized patients to support diagnosis of
      malnutrition by the Academy-A.S.P.E.N. malnutrition consensus recommended
      clinical characteristics.
AB  - BACKGROUND: The feasibility of accessing data in hospitalized patients to support
      a malnutrition diagnosis using the new Academy of Nutrition and Dietetics
      American Society for Parenteral and Enteral Nutrition (AND-A.S.P.E.N.) consensus
      recommended clinical characteristics of malnutrition is largely unknown. We
      sought to characterize baseline practice to guide the development of appropriate
      interventions for implementation of the recommended approach. MATERIALS AND
      METHODS: A cross-sectional survey was conducted of 262 consecutive adults who
      were referred for dietitian or nutrition support team assessments at 2 tertiary
      teaching hospitals in Pennsylvania. The availability of data to support the
      proposed AND-A.S.P.E.N. approach and the resulting malnutrition diagnoses were
      examined. RESULTS: Mean +/- SD age was 58.2 +/- 17.1 years, and half were female.
      Food intake history was available for 76%, weight history for 67%, and physical
      examination for loss of fat and muscle mass for 94% and for edema for 84%. Hand
      grip strength was not available. The prevalence of malnutrition among the
      patients referred for nutrition assessment was 6.7% moderate, 7.6% severe with
      acute illness; 12.2% moderate, 11% severe with chronic illness; and 0.8%
      moderate, 0.4% severe with social circumstances. Decline in typical food intake
      and weight loss were the most commonly used clinical characteristics. CONCLUSION:
      Data could generally be accessed to support the AND-A.S.P.E.N. consensus clinical
      characteristics for malnutrition diagnosis, but further testing in multiple care
      settings is needed before these observations may be generalized. Training in
      assessment methods and dissemination of the necessary tools will be necessary for
      full implementation.

PMID- 24301191
TI  - Acetosyringone promotes high efficiency transformation of Arabidopsis thaliana
      explants by Agrobacterium tumefaciens.
AB  - High frequency transformation of Arabidopsis thaliana leaf explants has been
      obtained using a disarmed Ti plasmid containing the coding region of a neomycin
      phosphotransferase gene (NPT II) as a selectable marker. The rate of
      transformation ranged from 55 to 63 percent when acetosyringone (AS), a natural
      wound response molecule, was added to an Agrobacterium tumefaciens culture prior
      to incubation with leaf segments. Without acetosyringone, the transformation rate
      was approximately 2 to 3 percent. Calli resistant to G418 were regenerated into
      mature flowering plants in the presence of 10 MUg/ml G418. Southern analysis and
      neomycin phosphotransferase assays confirmed the insertion and expression of the
      NPT II gene in regenerated Arabidopsis plants. 

PMID- 24301192
TI  - Architecture of a plant promoter: S1 nuclease hypersensitive features of maize
      Adh1.
AB  - S1 nuclease was used to probe the architectural characteristics of the maize
      alcohol dehydrogenase-1 gene promoter. Three sites were identified as
      hypersensitive to S1 digestion in supercoiled, but not linear plasmids containing
      the Adh1 gene. The sites mapped to areas located 65, 330 and 800 base pairs 5' to
      the start of transcription. In each case, the strand specific nicking pattern was
      determined with nucleotide level precision. The -65 site was found to be a
      homopurine/homopyrimidine tract. The -330 site mapped to the boundaries of a
      region of high Z-DNA potential and the -800 site mapped to a non-descript
      sequence. The possible biological significance of these sites is discussed. 

PMID- 24301193
TI  - Pea genes associated with non-host disease resistance to Fusarium are also active
      in race-specific disease resistance to Pseudomonas.
AB  - A given plant species is able to resist most of the potentially pathogenic
      microorganisms with which it comes in contact. This phenomenon, known as non-host
      resistance, can be overcome only by a very small number of 'true pathogens' which
      can use that plant as a host. In some cases, plants have developed mechanisms for
      overcoming infection by specific races or strains of a true pathogen. This race
      specific resistance can be easily manipulated into agronomically important
      cultivars by plant breeders. We have previously described nine cDNA clones which
      represent pea genes active during non-host resistance against the fungus Fusarium
      solani f. sp. phaseoli. In the present work, we have used these cDNAs as probes
      to compare non-host resistance with race-specific responses of peas against three
      races of Pseudomonas syringae pv. pisi. Five of the genes most active during non
      host resistance were also active in direct correlation with the phenotypic
      expression of resistance in race-specific reactions of five differential pea
      cultivars against three races of Pseudomonas syringae pv. pisi. 

PMID- 24301194
TI  - Sequencing and modification of psbB, the gene encoding the CP-47 protein of
      Photosystem II, in the cyanobacterium Synechocystis 6803.
AB  - The Photosystem II protein CP-47 has been hypothesized to be involved in binding
      the reaction center chlorophyll. The psbB gene, encoding this protein, was cloned
      from the genome of the cyanobacterium Synechocystis 6803, and sequenced. The DNA
      sequence is 68% homologous with that of the psbB gene from spinach, whereas the
      predicted amino acid sequence is 76% homologous. The hydropathy patterns of
      Synechocystis and spinach CP-47 are almost indistinguishable, indicating the same
      general CP-47 folding pattern in the thylakoid membrane in the two species. There
      are five pairs of histidine residues in CP-47 that are spaced by 13 or 14 amino
      acids and that are located in hydrophobic regions of the protein; these histidine
      residues may be involved in chlorophyll binding. Interruption of the psbB gene by
      a DNA fragment carrying a gene conferring kanamycin resistance results in a loss
      of Photosystem II activity. This indicates that an intact CP-47 is required for a
      functional Photosystem II complex, but does not necessarily indicate that this
      protein would house the reaction center. 

PMID- 24301195
TI  - Characterization of the TrnD, TrnK, PsaA locus of Euglena gracilis chloroplast
      DNA.
AB  - The EcoRI fragment Eco J' of Euglena gracilis chloroplast DNA has previously been
      identified as a tRNA coding locus. The nucleotide sequence of a 2.3-kb region of
      the Eco J' fragment known to contain the tRNA genes has been determined. This
      locus was found to contain two tRNA genes, trnD-GTC and trnK-TTT. Separated from
      the trnK locus by a 43-bp spacer is an open reading frame of 398 codons. The open
      reading frame is 73-75% homologous to the amino-terminal coding regions of the
      spinach and maize genes for the P700 chlorophyll a apoprotein of photosystem I.
      It has been identified as exon I of an intron-containing psaA gene. The exon is
      followed by an intron of at least 214 bp that has features characteristic of
      other Euglena chloroplast introns. Major chloroplast RNA transcripts of sizes
      5.5, 4.7, and 2.3 kb hybridize to a psaA-specific probe. The gene for a second
      photosystem I P700 apoprotein, psaB, has been located on an adjacent EcoRI
      fragment, Eco C. 

PMID- 24301196
TI  - The amino terminal region delimited by Met1 and Met 37 is an integral part of the
      32 kDa herbicide binding protein.
AB  - The 33.5 kDa precursor of the 32 kDa herbicide binding protein is encoded in the
      chloroplast by the psbA gene. Previous work on the gene and protein did not
      pinpoint the initiation site of translation in vivo. To resolve this issue,
      constructs containing full length, truncated or mutated psbA from Solanum nigrum
      were used as templates for in vitro transcription in an SP6-promoter directed
      system. The resulting RNAs were then translated in a reticulocyte lysate system.
      The SDS-PAGE and partial proteolysis patterns of the translation products
      demonstrate that constructs containing the first ATG codon (Met1) of the psbA
      open reading frame code for a full length precursor protein (33.5 kDa),
      irrespective of whether the second ATG codon (Met37) is replaced by site directed
      mutagenesis or not. However, a 5' deleted gene, lacking the codon for Met1 but
      containing the codon for Met37, codes for a truncated 29 kDa protein. It is
      concluded that the 33.5 kDa precursor protein and its 32 kDa maturation product
      initiate at Met1 of the psbA open reading frame. 

PMID- 24301198
TI  - Biotechnology news and view.

PMID- 24301197
TI  - Queuine in plants and plant tRNAs: Differences between embryonic tissue and
      mature leaves.
AB  - In eubacterial and eukaryotic tRNAs specific for Asn, Asp, His and Tyr the
      modified deazaguanosinederivative queuosine occurs in position 34, the first
      position of the anticodon. Analysis of unfractionated tRNAs from wheat and from
      tobacco leaves shows that these tRNAs contain high amounts of guanosine (G) in
      place of queuosine (Q). This was measured by the exchange of G34 for
      [(3)H]guanine catalysed by the specific tRNA guanine transglycosylase from E.
      coli. Upon gel electrophoretic separation of the labeled tRNAs, seven Q-deficient
      tRNA species including isoacceptors are detectable. Two are identified as
      cytoplasmic tRNAs(Tyr) and tRNA(Asp) and two represent chloroplast tRNA(Tyr)
      isoacceptors. In contrast to leaf cytoplasm and chloroplasts, wheat germ has low
      amounts of tRNAs with G34 in place of Q.A new enzymatic assay is described for
      quantitation of free queuine in cells and tissues. Analysis of queuine in plant
      tissues shows that wheat germ contains about 200 ng queuine per g wet weight. In
      wheat and tobacco leaves queuine is present, if at all, in amounts lower than 10
      ng/g wet weight. The absence of Q in tRNAs from plant leaves is therefore caused
      by a deficiency of queuine. Tobacco cells cultivated in a synthetic medium
      without added queuine do not contain Q in tRNA, indicating that these rapidly
      growing cells do not synthesize queuine de novo. 

PMID- 24301199
TI  - Sex, drugs, and violence: neuromodulation of attachment and conflict in voles.
AB  - Prairie voles (Microtus ochrogaster) are a rodent species that display socially
      monogamous pair-bonds, a behavior illustrated by several types of social
      interactions such as mating-induced partner preference, selective aggression
      toward conspecific strangers, and bi-parental care. Therefore, this species has
      provided an excellent opportunity for the study of pair-bonding and its
      underlying neurochemical mechanisms. This chapter discusses the utility of this
      unique rodent in the study of attachment and conflict, and reviews recent
      findings illustrating the neuromodulatory mechanisms underlying mating-induced
      partner preference and aggression. Finally, implications of research using this
      animal model in human mental health are also discussed. 

PMID- 24301200
TI  - Intermittent exposure to traces of green leaf volatiles triggers the production
      of (Z)-3-hexen-1-yl acetate and (Z)-3-hexen-1-ol in exposed plants.
AB  - Intermittent exposure during a period of 3 weeks of undamaged Arabidopsis plants
      to trace amounts of volatiles emitted by freshly damaged Arabidopsis plants
      resulted in an increase of subsequent artificial-damage-induced production of (Z)
      3-hexen-1-yl acetate and (Z)-3-hexen-1-ol in the exposed Arabidopsis plants when
      compared with Arabidopsis plants exposed to undamaged Arabidopsis plant volatiles
      (control plants). We previously showed that (Z)-3-hexen-1-yl acetate attracts a
      parasitic wasp, Cotesia glomerata. Thus, the induced production of this volatile
      explained our previously reported finding that, when artificially damaged, the
      exposed plants were more attractive to C. glomerata than control plants. 

PMID- 24301201
TI  - Importance of plant integrity in crop research, breeding, and production.
AB  - Plant integrity looks like a "very easy and expanded topic," but the reality is
      totally different. Thanks to the very high specialization of scientists, we are
      losing a holistic view of plants and are making mistakes in our research due to
      this drawback. It is necessary to sense a plant in their whole complexity--in
      both roots and shoot, as well as throughout their life cycles. Only such an
      integrated approach can allow us to reach correct interpretations of our
      experimental results.

PMID- 24301202
TI  - Pulmonary metastasectomy.

PMID- 24301203
TI  - Primary prevention research: Barriers, needs and opportunities.

PMID- 24301204
TI  - Perinatal support programs: A strategy for the primary prevention of child abuse.
AB  - Perinatal support programs are offering new hope for the prevention of child
      abuse. This article reviews the research stimulating these programs, details the
      prescribed components of perinatal programs according to the Interprofessional
      Task Force on Health Care of Women and Children and the National Committee for
      Prevention of Child Abuse, and discusses four demonstration projects currently
      being conducted. 

PMID- 24301205
TI  - Consultation to educational administrators.
AB  - A community mental health center had developed an innovative consultation program
      for school principals. Forty-five of the area's 95 school principals from 14
      districts are enrolled in the program. The services provided are individual
      consultation, support groups and conferences. The evaluation of the program
      consisted of a questionnaire and interviews. The individual consultation was
      perceived to be of greater value than the other services. Overall, the program
      appeared to help relieve the isolation of principals and provide them with a
      means for processing ideas and actions. The program did not appear to be as
      effective in increasing colleagueship and a support system among principals. 

PMID- 24301206
TI  - Putting secondary prevention to the test: A study of an early intervention
      strategy with disabled workers.
AB  - The enormous costs associated with physical and pyschiatric disability have
      camouflaged, in some ways, the utility of prevention in the area of disability.
      Overwhelmed by the needs of the severely disabled, funding and service agencies
      have been legislatively mandated to earmark their monies disproportionately for
      the most severely disabled rather than channeling funds toward early intervention
      services. The study described in this article is designed to measure the cost and
      health implications of an alternative allocation of resources for the disabled,
      to compare a secondary and tertiary prevention service. The preventive disability
      service that was tested was designed out of the results of a preliminary study of
      disability claimants, conducted at the same site. The study population was a
      sample of the claimants of the Health and Security Plan of a large urban union.
      Persons who filed claims with the Plan during 1974 were studied in terms of their
      demographic, employment and disability characteristics. High, moderate and low
      risk groups were identified; a specified subsample was targeted for testing the
      preventive service. 

PMID- 24301208
TI  - An unorthodox proposal for funding primary prevention.

PMID- 24301207
TI  - Parents and prevention: Seattle's year of the parent.

PMID- 24301209
TI  - Data on the reduction in improving effect of A.I. Bulls in relation to the
      genetic trend of the population.
AB  - In order to clarify the question of the reduction in improving effect of
      A.I.bulls in relation to the genetic trend of the population, the authors have
      carried out two model calculations: a) This one assumed different genetic
      progress as well as different improving effects of bulls. The duration and extent
      of improving effect have been examined. b) The data on an US-Holstein-Friesian
      elite population was processed to determine changes in improving effect during a
      period of 10 years, assuming 1 per cent genetic gain per year. Ten per cent of
      this elite population were chosen and examined as a 'nucleus
      population'.Conclusions are as follows: 1. In female populations representing
      continuous and considerable genetic progress, even bulls of excellent genetic
      merit can assure improvement for only a few years. 2. The improving effect may be
      referred to a definite population only if the progeny test results are directly
      related to the average of the population, or if these can be adjusted properly.
      3. A 'nucleus population', selected and maintained by high selection pressure,
      could have such a great genetic superiority that progress is assured for a long
      time in the 'population with high breeding value'. 4. A significant genetic
      advance has to be achieved, maintained and utilized in the sire-producing mating
      category. This requires reasonable rationalization of selection and mating,
      utilizing international gene-resources and continuous control of the breeding
      value of sires in the populations. 

PMID- 24301210
TI  - Are 'multiple cross-multiple pollen hybrids' an answer for productive populations
      in Brassica campestris (var.) Brown Sarson? : Part 2: evaluation of 'mucromphs'.
AB  - A set of 167 'mucromphs' was evaluated in their F1 generation for seven 'plant',
      four 'plot' and five 'ratio' characters. Methods of characterizing the parents
      and the hybrids on the basis of combining ability effects described in the first
      part were found to be efficient in identifying desirable cross combinations for
      pedigree breeding or generating composite populations. Order effects of multiple
      pollen combinations were found to be potent for a number of character components.
      High x Low cross-combinations were found to produce a high frequency of heterotic
      crosses followed by High x High. Selected biparental progenies, single crosses,
      three-way crosses and elite varieties were successful female parents and
      combinations of pollen from two varieties, one variety and three varieties were
      successful male parents, in that order, in producing significant heterosis in
      mucromphs. The relationship between general and specific combining ability on the
      one hand and realised heterosis on the other was discussed. 

PMID- 24301211
TI  - Distribution of S-alleles and breeding structure of Cape broccoli (Brassica
      oleracea var.'italica').
AB  - 182 plants representing 7 cultivars of Cape broccoli were tested for their S
      alleles using the standard Brassica S-allele collection. In all but 12 plants
      both S-alleles were identified. A total of 20 different S-alleles were found, 9
      of which occurred in the autumn types but not in the spring, 5 of which occurred
      in the spring types and not the autumn, and 6 of which were common to both. Most
      of the S-alleles detected in Cape broccoli were also found in Brussels sprouts or
      kales, but of the three which were not, two were confined to Cape broccoli while
      the third occurred only in Cape broccoli and Savoy cabbage. By far the commonest
      S-allele in Cape broccoli was S2, with an overall frequency of 35%. Three S
      alleles were found (S14, S25 & S45) which were completely recessive in the stigma
      in certain combinations. The general pattern of distribution of S-alleles in Cape
      broccoli, with highly unequal frequencies, was similar to that in Brussels
      sprouts. The results indicate a high level of outcrossing in Cape broccoli which
      has implications for the breeding of this crop. 

PMID- 24301212
TI  - Production of triploid plants from the immature and mature endosperm cultures of
      rice.
AB  - Triploid plants were induced to regenerate from immature and mature endosperm
      cultures of three cultivars of rice. The plants were subsequently established in
      the soil. The significance of the induction of genetic variability in the
      germplasm of rice is discussed. 

PMID- 24301213
TI  - Isolation and characterization of isonicotinic acid hydrazide-resistant mutants
      of Nicotiana tabacum.
AB  - Twenty stable variant lines resistant to isonicotinic acid hydrazide (INH), an
      inhibitor of the conversion of glycine to serine in the glycolate pathway, were
      isolated in cell cultures initiated from allodihaploid Nicotiana tabacum. Plants
      were regenerated from 13 of these lines and explants were tested for resistance.
      For some lines virtually all of the regenerated plants scored as resistant; for
      others a mixed population of sensitive and resistant plants were obtained. One or
      more plants from 5 lines were fertile, presumably as a result of spontaneous
      diploidization of cells in the plant or culture. Callus initiated from the seed
      progeny of these plants was resistant to INH confirming the characteristic as a
      stable mutation. Seedlings from all INH-resistant plants were small and slow
      growing, but the slow-growth trait could be separated from resistance in
      backcrosses of hybrids. In one case (line I21) crosses with sensitive lines show
      the resistant trait in that line to be dominant. 

PMID- 24301214
TI  - Linkage of the hordein loci Hor1 and Hor2 with the powdery mildew resistance loci
      Ml-k and Ml-a on Barley chromosome 5.
AB  - The linkage relationship among the loci Hor1, Hor2, Ml-k and Ml-a on the short
      arm of chromosome 5 was studied by progeny testing the F2 generation of two
      crosses. The loci Hor1 and Hor2 code for polypeptides of the storage protein
      hordein (prolamin) and the loci Ml-k and Ml-a determine the resistance reaction
      with some powdery mildew fungi cultures. The order of the loci is Ml-k, Hor1, Ml
      a, and Hor2, the first named being nearest the centromere. The recombination
      percentage between Hor1 and Hor2 was determined in the F1 and F2 generations in
      both crosses, the combined estimate being 7.4+/-0.9 per cent. The recombination
      percentage estimated between Ml-k and Hor1 was 4.0+/-1.3, between Hor1 and Ml-a,
      5.3+/-1.1, and between Ml-a and Hor2, 6.1+/-1.2. The estimates involving the Ml-
      loci were all probably a little too high. 

PMID- 24301215
TI  - Estimating heritability and genetic correlation between traits from generations
      F2 and F 3 of self-fertilizing species: a comparison of three methods.
AB  - Three methods of estimation of heritability and genetic correlation between
      traits in the F2 and F3 generations of self-fertilizing species were compared.
      The methods were: 1. Subtracting the estimates of environmental variances and
      covariances from the corresponding phenotypic estimates in the segregating
      generation which yields 'broad-sense' heritability and genetic correlation. 2.
      Analyses of variance and covariance of full-sib families; correlations were
      calculated from the between-families components and heritability was estimated by
      using intraclass correlation. 3. Offspring on parent regression for single traits
      and pairs of traits which yields estimates of heritability and genetic
      correlation. Theoretically, the family-analysis method is superior to the two
      others, because those estimates are less affected by non-additive genetic
      variance and covariance. Actual estimates for six traits in peanuts and their 15
      two-trait combinations were calculated only for the purpose of comparison between
      the three methods. These estimates seem to be in agreement with conclusions which
      were drawn from the theoretical considerations. 

PMID- 24301216
TI  - Isolation of a nitrate reductase deficient mutant of Pisum sativum by means of
      selection for chlorate resistance.
AB  - After EMS treatment of seeds of the Pisum variety 'Rondo' a chlorate resistant
      mutant was isolated which showed a decrease in the in vitro activity of the
      enzyme nitrate reductase of roughly 95%. The mutation is monogenic and recessive.
      The mutant shows a decrease in protein content, and an increase in the amount of
      nitrate accumulated and in the activity of the enzyme nitrite reductase. On a
      liquid nutrient medium containing nitrate as the sole nitrogen source and in
      soil, the mutant grows very poorly due to necrosis of the leaves. On liquid
      medium containing ammonium, either with or without nitrate, growth is as good as
      that of the parent variety. 

PMID- 24301217
TI  - Genetic effects of griseofulvin on plant cell cultures.
AB  - Griseofulvin induces metaphase arrest and polyploidization in plant cells in
      culture; after which a process of chromosome segregation follows. During this
      process spontaneous or induced recessive mutations become expressed through the
      formation of homozygotes or monosomics. This finding can be of use whenever the
      isolation of recessive mutations is needed and haploid culture is difficult. 

PMID- 24301218
TI  - Predictors of outcome in palliative colonic stent placement for malignant
      obstruction.
AB  - BACKGROUND: Emergency surgery for large bowel obstruction carries significant
      morbidity and mortality. After initially promising results, concerns have been
      raised over complication rates for self-expandable metal stents (SEMS) in both
      the palliative and bridge-to-surgery settings. This article documents the
      technique used at the authors' institution, and reports on success and
      complication rates, as well as identifying predictors of endoscopic
      reintervention or surgical treatment. METHODS: Data were collected for a
      prospective cohort of consecutive patients undergoing attempted colonoscopic SEMS
      insertion at a single institution between 1998 and 2013. Multivariable logistic
      models were fitted to assess possible predictors of endoscopic reintervention and
      surgical treatment. RESULTS: Palliative SEMS insertion was attempted in 146
      patients. Primary colorectal cancer was the most common cause of obstruction
      (95.2 per cent). The majority of patients (77.4 per cent) were treated in an
      acute setting, with a high technical success rate of 97.3 per cent. The
      perforation rate was 4.8 per cent and the 30-day procedural mortality rate 2.7
      per cent. No predictors of early complications were identified, although patients
      with metastases and those who received chemotherapy were more likely to have late
      complications. Some 30.8 per cent of patients required at least one further
      intervention, with 11.0 per cent of the cohort requiring a stoma. Endoscopic
      reintervention was largely successful. CONCLUSION: SEMS offer a valid alternative
      to operative intervention in the palliative management of malignant large bowel
      obstruction. Patients receiving chemotherapy are more likely to receive
      endoscopic reintervention, which is largely successful.

PMID- 24301219
TI  - Doping dependence of spin excitations and its correlations with high-temperature
      superconductivity in iron pnictides.
AB  - High-temperature superconductivity in iron pnictides occurs when electrons and
      holes are doped into their antiferromagnetic parent compounds. Since spin
      excitations may be responsible for electron pairing and superconductivity, it is
      important to determine their electron/hole-doping evolution and connection with
      superconductivity. Here we use inelastic neutron scattering to show that while
      electron doping to the antiferromagnetic BaFe2As2 parent compound modifies the
      low-energy spin excitations and their correlation with superconductivity (<50
      meV) without affecting the high-energy spin excitations (>100 meV), hole-doping
      suppresses the high-energy spin excitations and shifts the magnetic spectral
      weight to low-energies. In addition, our absolute spin susceptibility
      measurements for the optimally hole-doped iron pnictide reveal that the change in
      magnetic exchange energy below and above T(c) can account for the superconducting
      condensation energy. These results suggest that high-T(c) superconductivity in
      iron pnictides is associated with both the presence of high-energy spin
      excitations and a coupling between low-energy spin excitations and itinerant
      electrons.

PMID- 24301220
TI  - Evaluating space-time models for short-term cancer mortality risk predictions in
      small areas.
AB  - Current cancer mortality data are available with a delay of roughly three years
      due to the administrative procedure necessary to create the registries.
      Therefore, health agencies rely on forecast cancer deaths. In this context,
      statistical procedures providing mortality/incidence risk predictions for
      different regions or health areas are very useful. These predictions are
      essential for defining priorities for cancer prevention and treatment. The main
      objective of this work is to evaluate the predictive performance of alternative
      spatio-temporal models for short-term cancer risk/counts prediction in small
      areas. All the models analyzed here are presented under a general-mixed model
      framework, providing a unified structure of presentation and facilitating the use
      of similar tools for computing the prediction mean squared error. Prostate cancer
      mortality data are used to illustrate the behavior of the different models in
      Spanish provinces. 

PMID- 24301221
TI  - Biological maturation and social development: A longitudinal study of some
      adjustment processes from mid-adolescence to adulthood.
AB  - The role of biological maturity in behaviors in adolescence which most often are
      considered as negative by adults was investigated for a normal group of girls. In
      mid-adolescence early matured girls were found to play truant, smoke hashish, get
      drunk, pilfer, ignore parents' prohibitions, considerably more often than did
      late maturing girls. These differences between biological age groups were
      mediated by the association with older peer groups and they leveled out in late
      adolescence. Data on alcohol consumption and crime at adult age showed little
      association with biological maturation. A hypothesis was tested suggesting that
      early biological maturation may have negative long-term consequences within the
      education domain. In accord with this assumption, a considerably smaller
      percentage of girls among the early maturers had a theoretical education above
      the obligatory nine-year compulsory schooling than among the late maturing girls.
      The association between biological maturation and adult education was significant
      also after controlling for standard predictors of education, such as the girls'
      intelligence and the social status of the home. The requirement of conducting
      longitudinal studies when investigating issues connected with maturation was
      strongly emphasized. 

PMID- 24301222
TI  - The effects of delayed menarche in different contexts: Dance and nondance
      students.
AB  - The premise that effects of maturational timing are mediated by social context is
      explored by comparing adolescent girls in dance and nondance schools. Because the
      dance student must maintain a relatively low body weight, being a late maturer
      (who is often leaner than an on-time maturer) is expected to be more advantageous
      to the dancer than to the student not required to meet a weight standard. Girls
      aged 14 to 18 were seen; 276 attended private schools and 69 attended national
      ballet company schools. AllSs were weighed and measured and asked questions about
      their secondary sexual development, weight-related concerns, eating concerns,
      adult sex-role expectancies, body image, emotional functioning, and family
      relationships. Menarcheal age was used to classify girls as early (before 11.5
      years of age), on time (between 11.5 and 14 years), and late maturers (after 14
      years). More dance than non-dance school students were late maturers (55% versus
      29%). The dance students weighed less and were leaner, had higher eating scores,
      and had lower family relationship and impulse control scores than the comparison
      sample. Across groups, late maturing students weighed less, were leaner, and had
      lower diet and higher oral control scores than on-time maturers, with the
      differences more pronounced in the dance than nondance students. In addition, the
      on-time dancers had higher psychopathology, perfection, and bulimia scores and
      lower body image scores than the late maturing dancers. The findings are
      discussed in terms of a goodness of fit between the requirements of a social
      context and a person's physical and behavioral characteristics. 

PMID- 24301223
TI  - Menarcheal status and parent-child relations in families of seventh-grade girls.
AB  - The associations between menarcheal status and several child-rearing and outcome
      variables were examined for mother-daughter and father-daughter dyads. All
      variables were assessed with questionnaires as an extension of earlier
      observational studies. Analyses were conducted via multiple regression analyses
      wherein menarcheal status was treated as a continuous variable and was entered
      into the regression equation as a set of power polynomial terms. The results
      indicated that most of the significant relations occurred for the mother-daughter
      dyad, and most of these relations were curvilinear. When menarche occurs at or
      around the modal time, changes in parent-child relations may be best thought of
      as temporary perturbations, but when menarche occurs early the effects may
      persist. 

PMID- 24301224
TI  - Family contexts of pubertal timing.
AB  - This study examined the influence of pubertal timing upon family interactions in
      normal and psychiatric adolescent samples. An important feature of our approach
      is its emphasis upon micro-analysis of family behaviors (individual speeches) and
      family processes (theoretically specified speech pairings). Rather than assume
      that global family patterns (e.g., power) shift in response to pubertal changes,
      we follow how types of speeches and speech sequences are associated with
      different pubertal timing. Using the previously constructed family coding system,
      the Constrainig and Enabling Coding System, we found that on-time adolescents and
      their parents differed from both off-time groups (early or late). These results
      are discussed in terms of current implications and suggestions for future
      research. 

PMID- 24301225
TI  - Idiopathic precocious puberty in girls: Psychosexual development.
AB  - A promising model syndrome for the examination of the role of physical maturation
      in the development of female sexuality is idiopathic precocious puberty (IPP). In
      this first controlled study of psychosexual development in IPP females, 16
      females between 13 and 20 years of age with a history of IPP were compared to 16
      control subjects with a history of normal puberty pair-matched to the index
      subjects on the basis of sex, race, age, socioeconomic level, and menarcheal
      status. The psychosexual history and the current psychosexual status were
      assessed by a systematic half-structured interview. The IPP females on average
      passed the psychosexual milestones at an earlier age than their normal maturing
      peers, with a particularly early onset of masturbation. Those who were
      sociosexually active tended to report a higher total orgasmic outlet and a higher
      sex drive. There was no increase in homosexuality among IPP girls. The timing of
      puberty has a (modest) influence on psychosexual development in females. 

PMID- 24301226
TI  - Adolescent maturational changes and psychosocial development: A dynamic
      interactional perspective.
AB  - Models of reciprocal biological-psychosocial relations may be quite usefully
      studied in adolescence. This period of life represents a "natural laboratory" for
      assessing these relations, and may be an ideal "sample case" illustrating their
      role in life-span development. In this article a dynamic interactional model of
      these relations is described and evaluated. This model stresses that on the basis
      of his or her characteristics of individuality (e.g., bodily characteristics that
      result from his/her maturational status), an adolescent will evoke differential
      reactions in his/her socializing others; these reactions will feed back to the
      adolescent and influence his/her further development. The nature of the feedback
      (e.g., its positive or negative valence) will depend on the goodness of fit
      between the adolescent's individual characteristics and the "demands" (e.g., the
      preferences, expectations, values, or behaviors) of significant others (e.g.,
      parents, peers, teachers). The model is evaluated in regard to its use in
      understanding data pertinent to the role of characteristics of physical
      individuality in adolescent development. Conclusions pertain to the importance of
      studying the processes by which adolescents, and particularly early adolescents,
      attain good fits with their contexts. 

PMID- 24301227
TI  - E-H (E = R3Si or H) bond activation by B(C6F5)3 and heteroarenes; competitive
      dehydrosilylation, hydrosilylation and hydrogenation.
AB  - In the presence of B(C6F5)3 five-membered heteroarenes undergo dehydrosilylation
      and hydrosilylation with silanes. The former, favoured on addition of a weak
      base, produces H2 as a by-product making the process catalytic in B(C6F5)3 but
      also enabling competitive heteroarene hydrogenation. 

PMID- 24301228
TI  - A randomized, controlled, blinded study of the safety, immunogenicity and batch
      consistency of Aleph inactivated split influenza vaccine made in China in Chinese
      people.
AB  - To evaluate the safety, immunogenicity and batch consistency of Aleph inactivated
      split influenza vaccine, 3308 healthy Chinese people more than 3 years old were
      enrolled in a randomized, controlled, blinded study and divided into four age
      groups: 3-10 years, 11-17 years, 18-54 years, and more than 55 years. Each age
      group was then randomized (2:1) to receive either influenza vaccine or control
      vaccine (recombinant hepatitis B) for one dose. Also each influenza vaccine group
      was randomized (1:1:1) to receive three different batches of influenza vaccine.
      Systematic and local adverse reactions for 28 days after vaccination were
      recorded, and influenza antibody titer was determined by hemagglutination
      inhibition (HI) assay at 28 days after vaccination. There were significant
      differences in seroconversion and seroprotection rates achieved post-immunization
      of three strains of influenza antibody (H1N1, H3N2, B) between experimental group
      and control group in all age groups (P<0.05). In addition, there were no
      statistically significant differences in local and systematic reaction rates
      after vaccination between the experimental and control group in all age groups
      (P>0.05), except for the systematic reaction rates in the 18-54 years and >= 55
      years age groups (P<0.05). Thus, Aleph inactivated split influenza vaccine has
      good safety and immunogenicity. 

PMID- 24301229
TI  - Perception of preference and risk-taking in laparoscopy, transgastric, and rigid
      hybrid transvaginal NOTES for cholecystectomy.
AB  - QUESTIONS UNDER STUDY: Few data are available regarding patients' perceptions of
      new cholecystectomy (CC) techniques, in the context of the patients' risk
      behaviours. We investigated patients' preferences for transgastric pure natural
      orifice translumenal endoscopic surgery (NOTES; transgastric NCC) and rigid
      hybrid transvaginal NOTES CC (tvNCC) compared with the standard laparoscopic CC
      (SL-CC), and patients' risk behaviours. METHODS: A total of 140 inpatients
      scheduled for elective laparoscopic CC were enrolled in this prospective single
      centre study, from January 2009 to January 2010. Patients judged the potential
      advantages and disadvantages of transgastric NCC and tvNCC compared with SL-CC.
      The individual's risk behaviour was analysed by means of the validated 40-item
      Domain-Specific Risk Attitude Scale (DOSPERT). RESULTS: Of the 140 recruited
      patients, 57 (65% females; mean age 51.5 years) were analysed. Twenty-five
      percent of males opted for transgastric NCC and 75% opted for SL-CC. Among
      females, 10.8%, 37.8% and 51.4% opted for transgastric NCC, tvNCC and SL-CC,
      respectively. Faster convalescence was graded as the primary potential advantage
      of transgastric NCC, whereas the potential risk of long-term stomach injuries was
      considered a primary disadvantage. Females graded the reduction of hospital
      acquired morbidity as the primary advantage of tvNCC. The risk assessment showed
      significantly more risk-taking behaviour in the recreational domain of life among
      patients who opted for innovative surgical techniques than among those opting for
      conventional surgery. CONCLUSIONS: Transgastric NCC is rarely accepted by females
      but accepted by a quarter of males. Females consider rigid-hybrid tvNCC and SL-CC
      similarly attractive. Despite promising new techniques, three-quarters of male
      and one half of female patients still prefer the standard laparoscopic CC.

PMID- 24301231
TI  - Introduction to special topic fillers and injectables.

PMID- 24301232
TI  - A call to limit antibiotic use in acne.

PMID- 24301233
TI  - The effect of menstrual cycle on laser induced hyperpigmentation.
AB  - BACKGROUND AND OBJECTIVE: Laser induced post inflammatory hyperpigmentation PIH,
      is a complication seen mostly in dark skinned patients, it is not known whether
      giving the laser treatment at specific menstrual period days, may predispose to
      PIH. METHODS: Seven volunteers underwent fixed fractionated CO2 laser treatments
      at four predetermined days spanning the menstrual cycle. RESULTS: Two volunteers
      developed hypopigmentation while the rest had hyperpigmentation. In those who
      developed PIH, the pigmentation was most severe when done just before or after
      menstruation. CONCLUSIONS: Laser induced PIH risk may be influenced by the
      menstrual cycle.

PMID- 24301234
TI  - Facial volume augmentation in 2014: overview of different filler options.
AB  - Volume loss is considered to be one of the major contributors to facial aging.
      Therefore, the restoration of facial volume and contour changes has become an
      important treatment approach in aesthetic dermatology in recent years. In October
      2013 the FDA approved for the first time ever an injectable dermal filler for the
      augmentation of age-related volume loss. This low-molecular-weight (LMW) 20 mg/ml
      hyaluronic acid (HA) filler competes on the market with poly-L-lactic acid (PLLA)
      and calcium hydroxylapatite (CaHA), that have been used off-label for many years
      to restore age-related volume loss. The safety profile and efficacy of all three
      injectables has been intensively evaluated in innumerous clinical studies.
      However, each volume filler has its benefits and disadvantages, including usage,
      method of action and duration of effect that are reviewed in this article.

PMID- 24301235
TI  - Aesthetic applications of calcium hydroxylapatite volumizing filler: an evidence
      based review and discussion of current concepts: (part 1 of 2).
AB  - BACKGROUND: Calcium hydroxylapatite filler (CaHA; Radiesse) is a synthetic, non
      animal derived product composed of minerals that occur naturally in bone and
      teeth. Following its development in the US, initial approval by the US FDA for
      non-aesthetic indications and CE marking in Europe, it was used off FDA-labeling
      for aesthetic purposes. Its use has grown further since its FDA approval in 2006
      for long-lasting correction of moderate to severe wrinkles and folds. It is a
      popular filler for volume restoration to the face, and also to nonfacial areas
      such as the dorsum of the hands. METHODS: The first article of this two-part
      series provides an evidence-based review of study data pertaining to the
      mechanism of action and biocompatibility of CaHA filler, and its safety, efficacy
      and tolerability when used for aesthetic purposes. The review includes data from
      a number of prospective, controlled comparative studies, from several
      retrospective studies, and from a meta-analysis of reported complications from
      alloplastic filler procedures over a 20-year period. The study methodology and
      number of study subjects are sufficiently robust to provide a high Evidence Level
      for much of the data. RESULTS: CaHA has good safety, efficacy and tolerability
      profiles that are comparable to those of hyaluronic acid (HA) fillers. It
      provides an initial, immediate volume replacement for up to 12 months followed by
      longer term correction due to biostimulation, resulting in collagenesis. Evidence
      Level II studies show longevity of 30 months or more after nasolabial fold
      implantation. Other studies demonstrate the appropriateness of CaHA filler for
      volume restoration to areas including the mid face, lower face and hands. CaHA is
      classified as an adjustable filler, whereas HA is fully reversible by
      hyaluronidase digestion. For this reason, and also because of CaHA's high
      viscosity and elasticity, evidence-based and experiential consensus suggests its
      avoidance in highly mobile areas (e.g. lips) or in anatomically unforgiving areas
      (e.g. the periocular region), where there may be increased incidence of nodules.
      CONCLUSION: CaHA filler is safe, efficacious and well-tolerated when used
      appropriately. It is increasingly recognized that many patients require pan
      facial volume restoration, and that many can benefit from combined treatments.
      Therefore, CaHA and HA fillers may be considered complementary rather than
      competitive to each other. The second article of this series offers a discussion
      of product characteristics, scientific principles and injection techniques to
      optimize treatment with CaHA filler, including special considerations for
      avoidance and management of complications.

PMID- 24301236
TI  - Full-face injections of variable total doses of abobotulinum toxin type A: A
      randomized, phase IV clinical trial of safety and efficacy.
AB  - BACKGROUND: Botulinum toxin type A (BoNT-A) has been used for almost 20 years in
      cosmetic dermatology to reduce dynamic wrinkles on single or multiple facial
      areas. OBJECTIVE: To evaluate the safety and efficacy of full-face treatments
      with various total doses of abobotulinum toxin A (ABO). METHODS: A total of 90
      participants were enrolled. Subjects had at least two indications for BoNT-A
      treatments on each third of the face (upper, middle and lower). They were
      randomized into 3 groups, with pre-defined total dose range of ABO, varying from
      120 to 250 U. RESULTS: Most of the subjects were women (96.5%). The statistically
      significant improvement from baseline lasted for more than 24 weeks for glabellar
      lines, and more than 16 weeks for forehead wrinkles and crow's feet, all P<0.001,
      with no differences between groups. The most frequent adverse event (excessive
      perioral weakness) was related to high dose in the perioral area. CONCLUSIONS:
      This is the first study to compare safety and efficacy of different doses of ABO
      administered to the entire face simultaneously. As long as the recommended doses
      are used, concomitant injections of ABO are safe and efficient, with no increase
      in adverse events.

PMID- 24301237
TI  - Quality of life and satisfaction of patients after full-face injections of
      abobotulinum toxin type A: A randomized, phase IV clinical trial.
AB  - BACKGROUND: Although botulinum toxin type A (BoNT-A) has been used effectively
      and safely to reduce facial dynamic wrinkles, few studies assessed patients'
      quality of life and satisfaction after treatment. OBJECTIVE: To assess the
      quality of life and satisfaction of patients treated with full-face injections of
      variable doses of abobotulinum toxin A (ABO). METHODS: Ninety subjects were
      randomized into 3 different groups, receiving 120-165 U, 166-205 U and 206-250 U,
      respectively. WHOQOL- BREF and Satisfaction and Self-assessment Questionnaire
      (SSQ) were completed by subjects up to 6 months after treatment. RESULTS: Most of
      the subjects were women (96.5%). For the physical domain in WHOQOL, a difference
      was observed between baseline and visit 2 (p = 0.036). There was no difference
      between groups for mean grades regarding amount of wrinkles, beauty, harmony and
      symmetry. However, there was a significant difference in the mean grades between
      visits. Patients' opinions also showed an improvement in their self-image up to
      four months after treatment, according to the self-grading. CONCLUSION: The
      results presented in this study show improvements in patients' quality of life
      during the peak of action of BoNT-A treatment, regarding the physical aspect. In
      addition, patients reported good satisfaction after a full-face approach.

PMID- 24301238
TI  - Nonsurgical treatment options for basal cell carcinoma - focus on advanced
      disease.
AB  - Basal cell carcinoma (BCC) is the most common cancer in the world. It is
      typically slow growing and usually effectively managed with surgery. However,
      BCCs in some patients are unsuitable for surgery or the patient may prefer a
      nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary
      treatment of either low- or high-risk BCCs. It is associated with high cure
      rates, albeit somewhat lower than those observed with Mohs micrographic surgery
      for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy.
      Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and
      photodynamic therapy (PDT). These therapies are generally associated with
      somewhat lower clearance rates and/or higher recurrence rates than surgery or
      radiotherapy, although they may be suitable in patients with low-risk BCCs when
      surgery or radiotherapy are impractical or less appropriate. An appealing feature
      of PDT is excellent cosmesis, but PDT is not currently approved by the Food and
      Drug Administration (FDA), and regimens are not well standardized. Vismodegib is
      a first-in-class hedgehog pathway inhibitor and recent addition to the
      armamentarium for the treatment of advanced BCC.

PMID- 24301239
TI  - Evaluation of the safety and efficacy of a novel 1440nm Nd:YAG laser for neck
      contouring and skin tightening without liposuction.
AB  - BACKGROUND: Laser lipolysis is a less invasive approach to neck rejuvenation than
      open surgery or liposuction. Wavelengths utilized for lipolysis liquefy fat and
      induce collagen remodeling, which tightens skin. A new Nd:YAG device has recently
      been developed that emits energy at a wavelength of 1440nm; this wavelength is
      more highly absorbed by adipose tissue and water than other wavelengths currently
      available. OBJECTIVE: To test the safety and efficacy of a pulsed 1440nm Nd:YAG
      wavelength and side-firing fiber for the treatment of subcutaneous fat and skin
      laxity associated with the aging neck. METHODS: Twenty-four subjects aged 40 to
      65 years underwent laser lipolysis of the submental and anterior cervical areas.
      An average of 1205J per 5 x 5 cm square was delivered, with a maximum internal
      temperature setting of 47 degrees C. Cervicomental Angle Score (CAS), Global
      Aesthetic Improvement Scale (GAIS), subject and investigator satisfaction, and
      safety were assessed. RESULTS: At six months post-treatment, 79% of subjects had
      a significant improvement in the CAS (P<.001) and 79% demonstrated an improvement
      on the GAIS. Clinical improvement was marked and evident for all but one subject,
      with physician and patient satisfaction scores indicating overall satisfaction
      with the procedure and outcomes. Adverse events were mild and transient with no
      incidence of burns, seromas, hematomas, infection, or nerve damage. CONCLUSION:
      The 1440nm Nd:YAG device with the side-firing fiber was safe and effective for
      the treatment of subcutaneous fat and skin laxity in the neck. This device offers
      an alternative to selected individuals aged 40 and over who do not wish to
      undergo rhytidectomy.

PMID- 24301240
TI  - Resveratrol: a unique antioxidant offering a multi-mechanistic approach for
      treating aging skin.
AB  - Resveratrol is a botanical antioxidant with diverse biologic effects. In this
      paper we will review the unique antioxidant activity of resveratrol including its
      effects on mitochondrial function. The molecular signaling of resveratrol and
      cellular mechanisms that make this botanical active an important anti-aging
      ingredient for topical application will be discussed.

PMID- 24301241
TI  - Generational dermatology: model for prevention and multi decade approach toward
      the evolving, aging patient.
AB  - The proposed terminology Generational Dermatology encompasses prevention and
      involves medical, cosmetic, surgical and oncologic strategies over the decades to
      optimize skin performance throughout the course of a lifetime. Organ failure is
      the inability of the organ to perform its determined function as a part of normal
      physiology and it may be possible to take a Generational preventive approach
      toward reducing morbidities associated with the failure of our largest organ, the
      skin. Outside of skin cancer prevention efforts we have as a specialty primarily
      worked on the tertiary prevention realm. I advocate that we can increase our
      focus on the primary and secondary tiers where we as Dermatologists have the
      training and education to identify risk factors and detect early symptoms of skin
      disease. I appeal to the house of Dermatology to embrace this concept of
      Generational Dermatology as preventive medicine for the evolving aging patient.
      The practice of Generational Dermatology will decrease patient morbidity and
      bring down the cost of healthcare. Our global increased longevity increases the
      number of elderly worldwide. Longer lifespan means dermatologic needs will
      increase as the skin must perform its basic function longer. There are also new
      unknowns and skin issues which arise from large numbers of people in the 9th and
      10th decades. Generational Dermatology is well suited to be a model for
      prevention as our patient's age and we can intervene at any decade. I believe the
      specialty will increasingly focus on how the skin can optimally perform for a
      longer period. Lastly, the practice of Generational Dermatology unifies the house
      of Dermatology as we need the innovations and input of every subspecialty to
      contribute to the health of the people we serve.

PMID- 24301242
TI  - Clinical study results of desoximetasone spray, 0.25% in moderate to severe
      plaque psoriasis.
AB  - Two Phase 3, double-blind, randomized, vehicle-controlled parallel studies
      evaluated the efficacy and safety of desoximetasone spray 0.25%, a super-potent
      topical corticosteroid, twice daily vs vehicle spray twice daily for 28 days in
      adult patients with moderate to severe plaque psoriasis. At baseline and
      throughout the study, the severity of disease for the psoriatic lesions was
      assessed using the Physician Global Assessment (PGA) score and a target lesion
      was assessed using the Total Lesion Severity Score (TLSS). A designated psoriatic
      plaque lesion was selected as the target lesion upon enrollment and evaluated
      throughout the study to determine the TLSS. To qualify for study entry, the
      subject needed to exhibit a PGA score of 3 (moderate) or 4 (severe) for overall
      disease severity, and a target lesion with an area of at least 5 cm(2) that
      achieved a combined score TLSS of >=7, with a plaque elevation score of >=3 (at
      least moderate). The mean % BSA affected by psoriasis ranged from 13%-17% at
      baseline. In both Phase 3 studies, a statistically significantly greater
      percentage of subjects in the desoximetasone spray 0.25% compared to vehicle
      group achieved both Clinical Success and Treatment Success at Day 28. These
      results, which were the primary efficacy variables, demonstrated superior
      efficacy in the active study group for both overall improvement of plaque
      psoriasis (by PGA) and in the individual psoriasis lesion (by TLSS) designated at
      baseline as the most severely involved plaque (target lesion). Assessment of
      secondary efficacy variables in both Phase 3 studies showed that subjects
      receiving desoximetasone Spray 0.25% twice daily exhibited statistically
      significantly mean changes from Baseline to Day 28 in PGA, TLSS, and % BSA
      affected when compared to subjects receiving vehicle spray twice daily.
      Tolerability and safety were assessed at all study visits. No statistically
      significant differences were observed between study arms and no major safety
      signals related to AEs were noted. No stinging and burning were reported with the
      spray formulation. This Class I topical corticosteroid has shown to be safe and
      efficacious in moderate to severe plaque psoriasis.

PMID- 24301243
TI  - The treatment and demographics of warts: an analysis of national trends.
AB  - BACKGROUND: Verrucae (warts) are a very common dermatologic disease. They can be
      of cosmetic concern, cause physical discomfort, and predispose patients to
      certain malignancies. Management of warts has traditionally been based on
      anatomic location, clinical appearance, and patient preference. PURPOSE: To
      investigate trends in the treatment of warts, as well as patient demographics
      associated with the diagnosis of warts. METHODS: The National Ambulatory Medical
      Care Survey (NAMCS) was queried for data regarding patient visits associated with
      the diagnosis of warts from 1990 to 2009. RESULTS: There was a significant
      increase in the use of topical imiquimod during the study period, such that it
      became the most frequently used medication for warts. No statistically
      significant trends were detected regarding the frequency of treatment with
      medication only, procedure only, or combination treatment. In terms of patient
      demographics, there was an upward trend in regards to increasing patient age and
      the diagnosis of warts. However, there were no significant trends with respect to
      patient gender or race and the diagnosis of warts. LIMITATIONS: Warts not
      otherwise specified (NOS) was the reported diagnosis for more than eighty percent
      of patient visits for warts. Trends in the treatment of plantar warts could not
      be evaluated as the ICD-9 code designating this diagnosis was recently instituted
      in 2009. Data from NAMCS are cross-sectional in nature. CONCLUSIONS: The advent
      of a new therapy and shifts in population patterns have modified the
      epidemiologic profile and treatment of warts.

PMID- 24301244
TI  - Evaluating and treating the adult female patient with acne.
AB  - Acne vulgaris is a common disease of the pilosebacous unit that affects an
      estimated 40-50 million Americans. Greater than 95% of teenage boys and between
      83% and 85% of teenage girls suffer from acne. The condition frequently continues
      into adulthood. While boys more commonly suffer from acne in the teenage years,
      greater numbers of women suffer into adulthood. It is unclear if the number of
      post-adolescent women with acne is rising as compared to the past, or whether
      women are now seeking out treatment more than in the past.(4) Post-adolescent
      acne is a significant problem for women. One survey-based United States study
      found that approximately 50% of women continue to suffer from acne in their
      twenties, 35% in their thirties, 26% in their forties, and 15% in their fifties.
      The prevalence of acne was shown to be higher in women than in men in each of
      these age groups.(7) A similar study from Europe showed that beyond the age of
      23, acne is more prevalent in women than men. In their forties and fifties, 5%
      and 8% of women suffered from acne, respectively. Several other studies have
      provided similar data, showing that larger numbers of adult women suffer from
      acne as compared to age matched men. Acne is the number one reason that patients
      visit a dermatologist. While the mean age at which patients are seen for acne is
      24 years old, 10% of visits occur in patients in their mid-thirties and forties.
      Approximately two thirds of dermatology visits for acne are made by women, and
      one-third of total acne office visits are made by women over 25 years old. Acne
      patients suffer from a significant psychological burden, which has been compared
      to that of patients with systemic diseases like diabetes, asthma, arthritis, or
      epilepsy. Up to 50% of adolescents with acne experience disturbances to their
      psyche, including issues with body image, anxiety, depression, poor self-esteem,
      social impairment, and thoughts of suicide. Moreover, acne treatment is
      expensive. The average total cost of care related to an acne patient's visit to
      the dermatologist is estimated to be $689.(14)

PMID- 24301245
TI  - In vivo histological evaluation of non-insulated microneedle radiofrequency
      applicator with novel fractionated pulse mode.
AB  - INTRODUCTION: Microneedle radiofrequency is a novel method that allows non
      thermal penetration of the epidermis followed by RF coagulation in selected depth
      of the dermis surrounded by zone of non-coagulative volumetric heating. The first
      generation of Microneedle RF applicators used insulated needles. These treatments
      were limited by a few factors, including low volume of dermal heating, lack of
      effect in the papillary dermis and pinpoint bleeding during the treatment. The
      system tested in this study (EndyMed PRO, Intensif applicator, EndyMed Medical,
      Cesarea, Israel) utilizes special extra sharp tapered non-insulated microneedles
      and a special pulse mode, allowing full coagulation during treatment and higher
      effective volume of dermal heat. METHODS: After Ethics Committee approval, one
      female pig (Type Large white X Landrace, 34 Kg) was chosen for the study. The
      animal was anesthetized using Ketamine, Xylazin and Isofluran. The EndyMed PRO,
      Intensif applicator (was used for treatment with different needle depth
      penetration (1 mm-3.5 mm) and in multiple energy settings. Six mm punch biopsies
      were harvested for histological analysis at the following time points:
      immediately after the treatment, 4 days after the treatment and 14 days after the
      treatment. H&E and Masson-Trichrome stains were processed. RESULTS: Visual
      inspection of the treated skin, immediately after the treatment, revealed arrays
      of pinpoint erythematous papules surrounded by undamaged epidermal tissue.
      Treatment field showed no sign of bleeding. Mild to moderate Erythema and Edema
      developed a few minutes after the treatment, varying according to the total
      energy delivered. The histologies taken 4-day after therapy showed in all energy
      settings, dry micro crusts over the treatment zones, with full healing of
      epidermis. In the 14-day specimens there was a replacement of the crusts/debris
      by a normal looking stratum corneum with complete healing of epidermis and
      dermis. DISCUSSION: The current in vivo study confirms that the EndyMed PRO
      Intensif applicator effective and predictable tool to create cylindrical micro
      zones of coagulation in the papillary and reticular dermis with minimal damage to
      the epidermis. The histologies taken 4 days and 14 days after treatment show
      rapid epidermal renewal with predictable volume of coagulation in dermis related
      to the length of the needle and the power used. Coagulation of capillaries during
      treatment allows a dry treatment field. The predictability of the effect and
      minimal downtime may offer a significant advantage over treatments with ablative
      fractional lasers of insulated RF microneedles.

PMID- 24301246
TI  - Clinical equivalence of conventional OnabotulinumtoxinA (900 KDa) and
      IncobotulinumtoxinA (neurotoxin free from complexing proteins - 150 KDa): 2012
      multidisciplinary French consensus in aesthetics.
AB  - Botulinum neurotoxins are the most popular non-surgical treatments for aesthetic
      indications, but there is uncertainty about whether certain formulations are
      comparable in efficacy and safety and can be substituted for one another by a
      simple one to one dose conversion ratio. An expert panel of French practitioners
      was convened to establish a consensus on the clinical equivalence in efficacy and
      safety of OnabotulinumtoxinA (900 KDa) and IncobotulinumtoxinA (neurotoxin free
      from complexing proteins - 150 KDa). The consensus was divided into three
      sections incorporating a biological, bibliographic and clinical analysis of the
      two toxins. This included a review of the published data that have directly
      compared the two toxins for aesthetic indications and a survey of the panel's
      extensive clinical experience with the two toxins in terms of efficacy and
      safety. All panel members reviewed and endorsed the content of each section.
      Among this expert panel of French aesthetic physicians and biologists there was
      consensus that OnabotulinumtoxinA and IncobotulinumtoxinA are clinically
      equivalent in terms of efficacy and safety, and that a switch from one drug to
      the other can be made using a simple 1:1 conversion ratio.

PMID- 24301247
TI  - Blockade of melanin synthesis, activation and distribution pathway by a
      nonprescription natural regimen is equally effective to a multiple prescription
      based therapeutic regimen.
AB  - BACKGROUND: Disorders characterized by cutaneous hyperpigmentation (HP) are among
      the most common complaints in dermatologists' offices. These patients are also
      some of the most difficult to treat since current therapeutic regimens have high
      irritation rates and mediocre efficacy. Moreover, current regimens have the
      potential to induce post-inflammatory HP (PIH), a secondary disease that is more
      difficult to treat. OBJECTIVE: To measure the effectiveness of a novel blend of
      primarily natural ingredients that inhibits all but one of the steps in melanin
      synthesis, activation and distribution. Three common types of HP were treated and
      compared with one of the most commonly prescribed available regimens. This
      comprises two prescription products and two nonprescription products containing
      known depigmenting lightening ingredients. MATERIALS AND METHODS: The initial
      trial consisted of 56 females of 3 different races were treated in a 3-armed
      parallel, investigatorblinded prospective controlled clinical trial of 18 weeks
      duration. The treatment phase was 12 weeks long, followed by a 6 week,
      nontreatment regression phase. This trial was conducted in the winter at over
      6,000 feet above sea level. The natural ingredient (NI) blend consists of two
      cosmeceutical products together containing 22 ingredients. A second 1-year open
      trial of 31 panelists of 3 races was instituted to document continual improvement
      using both NI products without irritation and sensitization. RESULTS: The novel
      herbal blend regimens had comparable efficacy in treating HP and preventing
      rebound of mottled HP, dyschromia and melasma as the commercial regimen
      containing two prescription products. The 12-month open study demonstrated
      continued visible improvement of the HP with NI regimens without irritation and
      sensitization. CONCLUSION: The novel primarily natural ingredient product
      regimens are equally effective in treating three types of cutaneous HP as is a
      regimen containing prescription hydroquinone 4%, tretinoin 0.05% and two
      nonprescription leave on products.

PMID- 24301248
TI  - Predicting improvement in signs and symptoms of plaque psoriasis after 1 week of
      treatment with clobetasol propionate 0.05% spray.
AB  - One of the hurdles to effectively managing plaque psoriasis is lack of adherence
      to prescribed treatments. Up to 40% of subjects report they do not adhere to
      their medication for a variety of reasons. Earlier response to treatment may be a
      motivator for subjects to better adhere to treatment. Clobetasol propionate 0.05%
      spray (CPS) is a highly potent topical corticosteroid indicated for the treatment
      of moderate to severe plaque psoriasis that has efficacy as early as 1 week after
      initiating therapy. Using data from the 2 CPS pivotal trials, a post hoc analysis
      was performed to determine the relationship between week 1 improvements and week
      4 treatment success (defined as a score of 0 [clear] or 1 [almost clear] in
      overall disease severity [ODS]). Improvements in week 1 ODS and pruritus were
      predictive of week 4 treatment success. Subjects who had ODS or pruritus scores
      of moderate or better at week 1 tended to be treatment successes at week 4
      whereas no relationship between week 1 scores and week 4 treatment success was
      observed for those treated with vehicle spray. The results of this post hoc
      analysis indicate that early improvement correlates to treatment success.

PMID- 24301249
TI  - Efficacy and safety of IncobotulinumtoxinA for the treatment of platysmal bands
      of the aging neck: an open-label, prospective pilot study.
AB  - INTRODUCTION: IncobotulinumtoxinA (Xeomin(r)/Xeomeen(r)/Bocouture(r)/XEOMIN
      CosmeticTM; botulinum toxin type A, free from complexing proteins [150 kDa], NT
      201; Merz Pharmaceuticals GmbH, Frankfurt, Germany) is an effective and well
      tolerated treatment for a variety of facial wrinkles. OBJECTIVE: To determine the
      efficacy and safety of incobotulinumtoxinA for the treatment of platysmal bands.
      METHODS: Women, 35-65 years of age, with platysmal bands scoring 2 or 3 on the
      validated 5-point Merz dynamic platysmal bands scale received a total of 60 U
      incobotulinumtoxinA divided between four platysmal bands (20 U in both medial
      bands and 10 U in both lateral bands). Investigator assessments according to the
      5-point scale were made at baseline and from standardized clinical photographs
      taken at follow-up visits 14 +/- 2, 56 +/- 7 and 84 +/- 7 days after treatment.
      The global aesthetic improvement scale (GAIS) and a novel questionnaire were used
      to assess subject treatment satisfaction. Adverse events were recorded. RESULTS:
      Twenty-five women (mean age 51.8 years) were included in the study. With a
      responder defined as a subject with at least a 1-point improvement from baseline
      on the dynamic platysmal bands scale, the response rate at maximum contraction
      was 100% at Day 14 as assessed by the investigator. By the same definition, a
      high response rate (96%) was maintained at maximum contraction at Day 84.
      Subjects reported that, at Day 84, 86.3% of the maximal effect (defined as the
      effect on Day 14) persisted. Subject-reported satisfaction was high, as indicated
      by the self-assessment on the GAIS and results from the subject satisfaction
      questionnaire. Treatment- related adverse events were mild and reversible.
      CONCLUSION: IncobotulinumtoxinA is an effective, well-tolerated treatment for
      platysmal bands, with a high percentage of the treatment effect maintained at 3
      months after treatment. Investigator and subject assessments both indicated high
      levels of treatment satisfaction.

PMID- 24301250
TI  - An evaluation of the benefits of a topical treatment in the improvement of
      photodamaged hands with age spots, freckles, and/or discolorations.
AB  - BACKGROUND: Photoaging of the hands is common due to frequent exposure to
      environmental factors. OBJECTIVE: To evaluate the efficacy of a topically applied
      cream formulated with an alpha-hydroxy acid, depigmenting agents, and
      antioxidants to improve the appearance of characteristics associated with
      photodamaged hands. METHODS: This was a single-site, open-label study of a
      proprietary topical treatment (Vivite Vibrance Decollete, Allergan, Inc.) in
      adult female subjects with moderate-to-severe photoaging of the hands. The
      treatment was administered to the hands twice daily over an 8-week period.
      Treatment efficacy was assessed at baseline and weeks 4 and 8 using the
      Investigator Global Assessment (IGA) score based on the percentage coverage and
      color depth of photodamaged areas. The severity of age spots, freckles, and hand
      skin discoloration were also assessed; digital and ultraviolet photography of the
      hands was performed. Subject-reported assessments of treatment efficacy were
      evaluated using a questionnaire administered at week 8. Statistical significance
      was defined with an alpha set at P<=.05. RESULTS: Thirty-five subjects were
      enrolled with a mean age of 55.6 years; 33 subjects completed the study. The IGA
      of the appearance of hand photodamage improved from a mean (standard deviation)
      score of 5.0 (0.8) at baseline to 3.1 (1.5) and 2.6 (1.3) at weeks 4 and 8,
      respectively (1=mild; 9=severe). Based on expert-grader evaluation, subjects
      demonstrated statistically significant improvements from baseline in IGA at weeks
      4 and 8 in age spots and freckling at weeks 4 and 8, (P<.0003) and in skin
      discolorations at week 8 (P<.05). The majority of subjects reported that they
      perceived improvements in each of the 9 parameters associated with skin
      appearance. No adverse events were reported. CONCLUSIONS: The appearance of age
      related hand pigmentation characteristics were significantly improved at 4 and 8
      weeks of treatment. Subjects reported post-treatment improvements in other
      characteristics associated with healthy skin.

PMID- 24301251
TI  - An adverse effect of an injectable cosmetic procedure: a case of mistaken
      identities.
AB  - Minimally invasive cosmetic procedures are being performed at increasing rates.
      This is likely due to the combination of a growing aging population, an increased
      accessibility through non-physician providers, and a common association of
      "minimally invasive" with the concept of fewer side effects. Despite their
      overall successes, there are adverse effects associated with these procedures,
      which are most often related to injection location, amount, and technique. This
      case describes a patient who sought botulinum toxin injections to smooth the
      appearance of periorbital lines who presented 12 months later with chronic
      multiple palpable nodules in the injection sites. Histopathological evaluation
      demonstrated a foreign body reaction resembling the reaction against semi
      permanent or permanent fillers such as poly-L-lactic acid or
      polymethylmethacralate. Knowledge of the biochemical properties and life cycles
      of dermal fillers guided the decision to surgically excise the nodules, with
      cosmetically satisfactory results.

PMID- 24301252
TI  - Treatment of a symptomatic dermatofibroma with fractionated carbon dioxide laser
      and topical corticosteroids.
AB  - Dermatofibromas are benign skin lesions that may be treated if symptomatic or for
      cosmetic concerns. We present a case of an African American woman with an
      enlarging, pruritic dermatofibroma on the thigh that was treated with
      fractionated carbon dioxide (CO2) laser three times approximately 5 weeks apart.
      Between laser treatments, topical corticosteroids were applied to the lesion for
      a total of 13 weeks. The dermatofibroma completely flattened and became
      asymptomatic within 1 month after the final laser treatment. We hypothesize that
      the fractionated CO2 laser ablated a portion of the stromal component of the
      lesion and introduced microscopic channels that facilitated deeper penetration of
      the topical corticosteroids into the lesion. This is the first reported case
      demonstrating the successful treatment of a symptomatic dermatofibroma using
      combination therapy with fractionated CO2 laser and topical corticosteroids.

PMID- 24301253
TI  - News, views, and reviews. Valeant pharmaceuticals latest investment: the fight
      against domestic violence.

PMID- 24301254
TI  - Geographic divergence of "Sulfolobus islandicus" strains assessed by genomic
      analyses including electronic DNA hybridization confirms they are geovars.
AB  - Ten well-annotated genomes of "Sulfolobus islandicus" strains from different
      geographic locations have been released at the NCBI database. Whole genome based
      composition vector trees indicate that these strains show the same branching
      patterns as originally reported by multi-locus sequence analysis. To determine
      whether the ten strains meet the criteria for separate species, DNA-DNA
      hybridization (DDH) was performed in silico. DDH values of strains from the same
      geographic location, i.e., Iceland, Kamchatka and North America, ranged from 82.4
      to 95.4 %, clearly qualifying them as members of the same species. The lowest DDH
      values found between locations ranged from 75.5 to 76.6 %, which exceed the 70 %
      DDH threshold for a species thereby indicating they are all members of the same
      species based on the currently accepted definition. The clear divergences of
      strains from the different geographic locations are sufficiently great to
      consider them as separate geovars. "S. islandicus" has not yet been validly named
      and a type strain has not been deposited in culture collections. We urgently
      recommend that those who study the organism fulfill the criteria of the
      International Code of Nomenclature of Bacteria in order to designate a type
      strain and to identify and deposit related strains of this species to make them
      available to the broader scientific community.

PMID- 24301256
TI  - A calorimetric study of the hydrolysis and peroxide complex formation of the
      uranyl(VI) ion.
AB  - The enthalpies of reaction for the formation of uranyl(vi) hydroxide
      {[(UO2)2(OH)2](2+), [(UO2)3(OH)4](2+), [(UO2)3(OH)5](+), [(UO2)3(OH)6](aq),
      [(UO2)3(OH)7](-), [(UO2)3(OH)8](2-), [(UO2)(OH)3](-), [(UO2)(OH)4](2-)} and
      peroxide complexes {[UO2(O2)(OH)](-) and [(UO2)2(O2)2(OH)](-)} have been
      determined from calorimetric titrations at 25  degrees C in a 0.100 M tetramethyl
      ammonium nitrate ionic medium. The hydroxide data have been used to test the
      consistency of the extensive thermodynamic database published by the Nuclear
      Energy Agency (I. Grenthe, J. Fuger, R. J. M. Konings, R. J. Lemire, A. B.
      Mueller, C. Nguyen-Trung and H. Wanner, Chemical Thermodynamics of Uranium, North
      Holland, Amsterdam, 1992 and R. Guillaumont, T. Fanghanel, J. Fuger, I. Grenthe,
      V. Neck, D. J. Palmer and M. R. Rand, Update on the Chemical Thermodynamics of
      Uranium, Neptunium, Plutonium, Americium and Technetium, Elsevier, Amsterdam,
      2003). A brief discussion is given about a possible structural relationship
      between the trinuclear complexes [(UO2)3(OH)n](6-n), n = 4-8. 

PMID- 24301255
TI  - Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase
      activity in brain of streptozotocin-induced diabetic rats.
AB  - We investigated the efficacy of rosmarinic acid (RA) in preventing lipid
      peroxidation and increased activity of acetylcholinesterase (AChE) in the brain
      of streptozotocin-induced diabetic rats. The animals were divided into six groups
      (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and
      diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures
      (striatum, cortex and hippocampus) were removed for experimental assays. The
      results demonstrated that the treatment with RA (10 mg/kg) significantly reduced
      the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum
      (47%) of diabetic rats when compared with the control. In addition, it was found
      that hyperglycaemia caused significant increased in the activity of AChE in
      hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the
      control. On the other hand, the treatment with RA reversed this effect to the
      level of control after 3 weeks. In conclusion, the present findings showed that
      treatment with RA prevents the lipid peroxidation and consequently the increase
      in AChE activity in diabetic rats, demonstrating that this compound can modulate
      cholinergic neurotransmission and prevent damage oxidative in brain in the
      diabetic state. Thus, we can suggest that RA could be a promising compound in the
      complementary therapy in diabetes.

PMID- 24301257
TI  - New approach for structural characterization of planar sets of nanoparticles
      embedded into a solid matrix.
AB  - In this work we demonstrate that Medium Energy Ion Scattering (MEIS) measurements
      in combination with Transmission Electron Microscopy (TEM) or Grazing Incidence
      Small Angle X-Ray Scattering (GISAXS) can provide a complete characterization of
      nanoparticle (NP) systems embedded into dielectric films. This includes the
      determination of the nanoparticle characteristics (location, size distribution
      and number concentration) as well as the depth distribution and concentration of
      the NP atomic components dispersed in the matrix. Our studies are performed
      considering a model case system consisting of planar arrangements of Au NPs (size
      range from 1 to 10 nm) containing three distinct Au concentrations embedded in a
      SiO2 film.

PMID- 24301258
TI  - Hybrid genes in the analysis of transformation conditions : I. Setting up a
      simple method for direct gene transfer in plant protoplasts.
AB  - Direct gene transfer into plant protoplasts has been recently developed, and
      conditions for high frequency transformation of SR1 tobacco protoplasts
      established. In this paper we analyse numerous transformation parameters in a
      comparative study on SR1 Nicotiana tabacum and N. plumbaginifolia, and report on
      a simple chemical technique for very efficient protoplast transformation. It is
      based on the synergistic interaction of MgCl2 and PEG. The technique yielded up
      to 1400 transformants per 3*10(5) treated N. tabacum protoplasts (up to 4.8% of
      the survivors, late selected clones). Using N. plumbaginifolia, the frequencies
      were 10-fold lower, indicating that the 'competence' for transformation has a
      species-specific component. 

PMID- 24301259
TI  - Regulation of gene expression of ribulose bisphosphate carboxylase in greening
      pea leaves.
AB  - Ribulose bisphosphate carboxylase/oxygenase (RuBisCO) is composed of two
      subunits, the chloroplastcoded large subunit (LS) and the nuclear-coded small
      subunit (SS). The effects of different light doses on the levels of the large
      subunit gene (rbcL), the rbcL and the rbcS mRNAs, and the rate of synthesis of
      RuBisCO were followed during greening. The rbcL gene dosage changed in response
      to light whereas the level of the rbcL mRNA changed independently of the gene
      dosage. This suggests that the expression of the rbcL gene is transcriptionally
      regulated and that the change in gene dosage only partially contributes to the
      increase in the mRNA. It appeared that the RuBisCO synthesis rate was
      proportional to the rbcS mRNA level rather than rbcL mRNA level. These results,
      taken together with the earlier observations of many researchers, suggest that
      RuBisCO synthesis in greening pea leaves is controlled primarily at the level of
      transcription of both genes and is fine-tuned at the post-transcriptional level
      in chloroplasts, so that the amount of LS is almost stoichiometric to that of SS.

PMID- 24301260
TI  - Tomato protoplast DNA transformation: physical linkage and recombination of
      exogenous DNA sequences.
AB  - Tomato protoplasts have been transformed with plasmid DNA's, containing a
      chimeric kanamycin resistance gene and putative tomato origins of replication. A
      calcium phosphate-DNA mediated transformation procedure was employed in
      combination with either polyethylene glycol or polyvinyl alcohol. There were no
      indications that the tomato DNA inserts conferred autonomous replication on the
      plasmids. Instead, Southern blot hybridization analysis of seven kanamycin
      resistant calli revealed the presence of at least one kanamycin resistance locus
      per transformant integrated in the tomato nuclear DNA. Generally one to three
      truncated plasmid copies were found integrated into the tomato nuclear DNA, often
      physically linked to each other. For one transformant we have been able to use
      the bacterial ampicillin resistance marker of the vector plasmid pUC9 to 'rescue'
      a recombinant plasmid from the tomato genome. Analysis of the foreign sequences
      included in the rescued plasmid showed that integration had occurred in a non
      repetitive DNA region. Calf-thymus DNA, used as a carrier in transformation
      procedure, was found to be covalently linked to plasmid DNA sequences in the
      genomic DNA of one transformant. A model is presented describing the fate of
      exogenously added DNA during the transformation of a plant cell. The results are
      discussed in reference to the possibility of isolating DNA sequences responsible
      for autonomous replication in tomato. 

PMID- 24301261
TI  - Nodulin gene expression during soybean (Glycine max) nodule development.
AB  - In vitro translation products of total RNA isolated from soybean nodules at
      successive stages of nodule development were analyzed by two-dimensional gel
      electrophoresis. In that way the occurrence of over 20 mRNAs specifically
      transcribed from nodulin genes was detected. The nodulin genes could be divided
      into two classes according to the time of expression during nodule development.
      Class A comprises at least 4 nodulin mRNAs which are found when a globular
      meristem is present in the root cortex. These class A nodulin genes have a
      transient expression. Class B nodulin genes are expressed when the formation of a
      nodule structure has been completed. Bradyrhizobium japonicum nod (+) fix(
      )mutants, with large deletions spanning the nif H,DK region, still induced
      nodules showing normal expression of all nodulin genes, indicating that the nif
      H,DK region is not involved in the induction of nodulin genes. In nodules induced
      by Bradyrhizobium japonicum nod (+) fix(-)mutant HS124 the bacteria are rarely
      released from the infection thread and the few infected cells appear to be
      collapsed. All class A and class B nodulin genes are expressed in HS124 nodules
      with the exception of 5 class B genes. 

PMID- 24301262
TI  - Gene expression in Brassica campestris showing a hypersensitive response to the
      incompatible pathogen Xanthomonas campestris pv. vitians.
AB  - Xanthomonas campestris pv. vitians, a pathogen of lettuce, elicits a
      hypersensitive response within 12 hours of inoculation into Brassica leaves,
      characterized by tissue collapse, loss of membrane integrity, vein blockage and
      melanin production. In contrast, the compatible pathogen, X. c. pv. campestris,
      has no visible effects on leaves for 48 hours, after which inoculated areas show
      chlorosis which eventually spreads, followed by rotting.mRNA was prepared from
      leaves inoculated with suspensions of both pathovars or with sterile medium up to
      24 hours following inoculation. In vitro translation of total and poly A(+) RNA
      in rabbit reticulocyte lysate in the presence of (35)S methionine followed by
      separation of the polypeptide products by 2D-PAGE, allowed comparison of the
      effects of these treatments on plant gene expression. Major changes in gene
      expression were observed as a consequence of the inoculation technique. In
      addition, after inoculation with X. c. vitians, up to fifteen additional major
      polypeptides appeared or greatly increased by four hours. Some of these had
      disappeared by nine hours and several more had appeared. No major polypeptides
      disappeared or decreased greatly in intensity following inoculation with X. c.
      vitians. 

PMID- 24301263
TI  - Chloroplast DNA gyrase and in vitro regulation of transcription by template
      topology and novobiocin.
AB  - We have examined the effects of novobiocin and template topology on the
      transcription of two chloroplast genes encoding the large subunit of ribulose 1,5
      bisphosphate carboxylase (rbcL) and the beta subunit of the chloroplast ATPase
      (atpB), in an in vitro transcription system. The template topology was monitored
      by agarose gel electrophoresis while the in vitro transcripts were determined by
      5' S1 nuclease analysis under identical conditions. We discovered that our
      chloroplast transcription extracts contain a DNA gyrase activity and a
      chromatographically separable topoisomerase I activity. Incubation of a
      supercoiled template with the extracts under the same conditions in which
      transcription assays were carried out leads to a decrease in the supercoiled from
      and concomitant appearance of distinct topoisomers. More extensive relaxation of
      the supercoiled template occurs when nucleotide triphosphates are omitted from
      the reaction mixture or when a low concentration (25 MUg/ml) of novobiocin is
      added. Higher concentrations (>= 250 MUg/ml) of the drug, however, also inhibit
      the topoisomerase I activity. The transcription of the atpB gene is inhibited by
      lower concentrations of novobiocin as compared to the rbcL gene in the same
      reaction mixture. Relaxed, closed circular template and linearized DNA are not
      substrates for chloroplast transcription extracts, although they are transcribed
      accurately by the E. coli RNA polymerase under our conditions. Control of in
      vitro transcription of the two chloroplast genes by template topology can also be
      demonstrated by modulating the relative activity for the topoisomerases in the
      transcription extract. Our results suggest that changes in template topology may
      be a mechanism by which chloroplast genes are differentially regulated and the
      chloroplast DNA gyrase and topoisomerase I are key enzymes for this mode of
      regulation in vivo. 

PMID- 24301264
TI  - cDNA cloning and developmental expression of pea nodulin genes.
AB  - A cDNA library prepared from pea nodule poly(A)(+) RNA was screened by
      differential hybridization with cDNA probes synthesized from root and nodule RNA
      respectively. From the cDNA clones that hybridized exclusively with the nodule
      probe five clones, designated pPsNod 6, 10, 11, 13 and 14 and each containing
      unique sequences, were further characterized together with one leghemoglobin and
      one "root-specific" cDNA clone. In vitro translation of RNA selected by the
      pPsNod clones showed that the corresponding genes encode nodulins with molecular
      weights ranging from 5 800 to 19 000. During pea root nodule development
      expression of the five PsNod genes starts more or less concomitantly with the
      onset of nitrogen fixing activity in the nodules and the time course of
      appearance and accumulation of the nodulin mRNAs is similar to that of
      leghemoglobin mRNA. In ineffective pea root nodules expression of the PsNod genes
      is induced but the final accumulation levels of the mRNAs are markedly reduced to
      various degrees. The expression of another nodulin gene, designated ENOD2, was
      followed using a heterologous soybean cDNA clone as probe. In pea root nodules
      the ENOD2 gene is expressed at least five days before the PsNod and leghemoglobin
      genes, and in contrast to the PsNod mRNAs the concentration of the ENOD2 mRNA is
      the same in wild type and fix (-) nodules. The results described suggest that in
      root nodules several regulatory mechanisms exist which determine the final
      nodulin mRNA amounts accumulating in the root nodule. 

PMID- 24301265
TI  - Intralesional immunotherapy for melanoma.
AB  - Intralesional immunotherapy of melanoma has two complementary aims. One is to
      cause regression of the injected metastasis. The other is to incite or modulate
      systemic immune responses in such a way that non-injected metastases will also
      undergo regression. A number of phase 1 and phase II studies with cytokines,
      viral, or bacterial agents have been conducted but their use has remained
      sporadic and has not progressed to become established treatments. Two treatments
      have progressed to randomized phase III studies. The most promising of these is
      based on intralesional injection of a genetically modified herpes simplex virus
      (HSV) (T-Vec). Initial results have shown a significant effect on durable
      response rates (DRR) but effects on overall survival remain under study. The
      second involved injection of plasmids coding for the HLA B7 antigen (Allovectin).
      Despite encouraging early results the treatment did not reach its endpoints and
      its use has been discontinued. A phase II study involving intralesional injection
      of oncolytic A21 coxsackie virus (Cavatak) is also under way and is showing
      promise.

PMID- 24301266
TI  - Polymyalgia rheumatica.

PMID- 24301267
TI  - Friedreich ataxia.

PMID- 24301268
TI  - World could eliminate health inequalities between nations by 2035.

PMID- 24301269
TI  - High Court forced mentally ill woman to have caesarean section, newspaper claims.

PMID- 24301270
TI  - Experts call for NICE to resume work on sex education halted by the coalition
      government.

PMID- 24301271
TI  - Public hostility grows to private companies' expansion in the NHS.

PMID- 24301272
TI  - A prevention approach to critical life events of the elderly.
AB  - Professionals interested in aging and mental health have not fully considered
      preventive efforts. In this article, we present a conceptual framework and
      rationale for developing preventive interventions focused on older adults. In
      addition, an example is presented of preventive programming which uses an
      existing community dissemination network. 

PMID- 24301273
TI  - The evaluation of a kindergarten social problem solving program.
AB  - The present study evaluated the effectiveness of a Social Problem Solving (SPS)
      competence training program for kindergartners, and examined relationships
      between SPS skill and adjustment gains. Subjects included 63 suburban middle
      classSs from three classes, who participated in the 42 lesson program, and 46
      comparisonSs from two classes, who did not. Subjects were evaluated on problem
      solving, peer sociometric and teacher adjustment ratings. Program children gave
      significantly more, and better, solutions, and fewer irrelevant responses to
      interpersonal problems. They also improved more than comparisonSs on several
      teacher-rated dimensions of adjustment. Direct linkages between skill and
      adjustment gains, however, were not found. 

PMID- 24301274
TI  - Between the dream and the reality: A look at programs nominated for the lela
      rowland prevention award of the national mental health association.
AB  - The 67 programs nominated for the 1980 Lela Rowland Prevention Award are
      discussed. Twelve outstanding programs are described individually. All programs
      are applauded for their efforts and accomplishments; more scientific evaluation
      and assessment of prevention programs is recommended in order to demonstrate that
      prevention is effective at accomplishing its goals. 

PMID- 24301275
TI  - A funny thing happened on the way to the community: Consultation and education in
      community mental health centers, or how I learned to stop worrying about
      prevention and love third-party payments.
AB  - A professional meeting provides an opportunity for a discussion between a
      formerly idealistic director of a consultation and education program of a
      community mental health center, and an academic colleague. The problems of
      promoting prevention are described in the context of economic pressures. 

PMID- 24301276
TI  - Brief notes.

PMID- 24301277
TI  - Positive youth development: Prevention as a process of positive community change.

PMID- 24301278
TI  - First you have to get their attention ...in Calgary, Saskatchewan, Quebec, and
      Nova Scotia.

PMID- 24301279
TI  - Primary prevention program clearinghouse psychology Department-Dewey Hall
      University of Vermont, Burlington, VT. 05405.

PMID- 24301280
TI  - Cardiac surgery in a patient with pemphigus vulgaris: anesthetic and surgical
      considerations.
AB  - Pemphigus vulgaris is an autoimmune disorder that causes blistering of the skin
      and mucous membranes. We present a patient with pemphigus vulgaris who required
      combined coronary artery bypass grafting and mitral valve repair. The challenges
      that we faced and modifications to the technique required in this situation are
      described and reviewed. 

PMID- 24301281
TI  - Nucleolar organizing chromosomes ofRicinus.
AB  - Pachytene chromosome morphology was compared in nine races ofRicinus communis L.
      (2n = 20), using pollen mother cells (PMCs) and light microscopy. Of the ten
      bivalents, only the two possessing nucleolar organizing regions (NORs),
      chromosomes 2 and 7, exhibit structural variations among the races. The NORs are
      located in the short arms of these two chromosomes. Most of the observed
      structural variations affect these short arms, which are similar morphologically
      and consist largely of heterochromatic segments. The PMCs contain a single
      nucleolus and this is associated with the NOR of each of the two chromosomes at a
      particular frequency in each race. In eight races, a nucleolar constriction (NC)
      is present in either chromosome 2 or chromosome 7. In these races, the nucleolus
      is associated with the chromosome possessing an NC at a frequency of 100% and
      with the chromosome lacking an NC at a frequency ranging between 5.6 and 100%,
      depending upon the race. No microscopically visible NC is present in the ninth
      race. In this race, the nucleolus is associated with both chromosomes 2 and 7 at
      a frequency of 100%. The association of the nucleolus with a chromosome
      possessing an NC is at the NC and with a chromosome lacking an NC is at the
      terminal heterochromatic segment of the short arm. Several interpretations are
      offered to account for the variations in frequency of association between the
      nucleolus and each of the nucleolar organizing chromosomes. It is suggested that
      the two non-linked NORs have evolved through some intragenomic changes rather
      than polyploidy, that this species is highly intolerant to structural variations
      other than those occurring in or near the NORs, and that structural variations in
      the nucleolar organizing chromosomes are not associated with racial variations in
      plant phenotype. 

PMID- 24301282
TI  - Chromosomal and embryological analyses in sexual x apomictic hybrids ofPanicum
      maximum Jacq.
AB  - Cytological analyses in series of crosses between 7 sexual pistillate and 8
      apomictic staminate parents of speciesPanicum maximum (Gramineae) are reported.
      Although these 15 progenitors were tetraploid (2n = 32), 2 dihaploids (2n = 16),
      45 hexaploids (2n = 48) and 5 octoploids (2n = 64) were observed among 333
      progeny plants. The role of unreduced gametes as the originators of polyploidy is
      discussed in relation to the so-called 'elements of apomixis'. The 2 dihaploids
      appeared to be sexual while the hexaploids and octoploids were all apomictic. At
      the tetraploid level sexual and apomictic hybrids segregated in a ratio close to
      1?1. These results were then compared to those already obtained from studies on
      other tropical grasses and indicate a simple genetic determinism for gametophytic
      apomixis. 

PMID- 24301283
TI  - An investigation into the mechanism for reduced seed yield inLotus corniculatus.
AB  - A study of seed position in the pod ofLotus corniculatus L. cv. 'Mirabel'
      (Fabaceae) suggested that reduced seed set after self-pollination is not due to
      an inability of the self-pollen tube to reach the end of the ovary. As in other
      cultivars, it has been demonstrated that cultivar 'Mirabel' produced less seed
      per pod and shorter pods after self- than after cross-pollination. No differences
      were noted for percent germination of seeds produced by both types of pollination
      indicating that the number of seeds per pod is a reliable index of the ultimate
      productive potential of the pollination. 

PMID- 24301284
TI  - Isozymic gene linkage map of the tomato: Applications in genetics and breeding.
AB  - New linkage data are presented for the situation of five previously unlocated
      isozymic loci of the tomato and closely related species with homosequential
      chromosomes.Prx-1 lies on chromosome 1, where it is also linked withSkdh-1; Aps-2
      is linked withGot-4 on chromosome 8;Tpi-2 has been allocated to chromosome 4; and
      a linkage has been detected betweenPgi-1 andEst-4, whose respective chromosome
      has not yet been determined. These and previously published data have been
      summarized in the form of an isozyme linkage map. Twenty-two loci have thus been
      mapped on nine of the twelve tomato chromosomes. We discuss some new applications
      of mapped isozymic genes. In certain types of segregations, isozymic genes are
      far more efficient than morphological markers in providing linkage information.
      They greatly expedite the cytogenetic investigation of species hybrids and can be
      utilized to facilitate backcross transfers of genes from wild to cultivated taxa.

PMID- 24301285
TI  - The basis for grain yield differences in mungbean cultivars and identifications
      of yield limiting factors.
AB  - Eight mungbean cultivars, selected from a cultivar collection on the basis of
      their grain yield, were grown in a replicated experiment. Morphological and
      physiological components contributing to grain yield were analysed. The principal
      yield limiting factor and the desirable yield component of each cultivar have
      been identified. The rate of dry matter accumulation was low in all cultivars. It
      is suggested that for a short duration crop like this, selection for rapid rate
      of dry matter increase would be advantageous. However, it should also be
      associated with a high partitioning efficiency (Harvest index). The top yielding
      cultivar had high biological yield and productive racemes. 

PMID- 24301286
TI  - F1 hybrid versus 32 selected F7 lines performance of common winter wheat
      (Triticum aestivum ssp. vulgare).
AB  - One F1 common wheat hybrid ('Zlatna Dolina' x 'Primepi') which had exhibited
      significant heterosis in a previous study was compared with 32 F7 lines selected
      from the same cross. The yield test was planted in the 1976-1977 season at two
      locations: Zagreb, Yugoslavia (optimal environment) and Hutchinson, Kansas, USA
      (stress environment). The purpose of this experiment was to determine if a
      homozygous segregant superior to the F1 hybrid could be obtained from the same
      cross combination.Heading date, plant height, disease incidence, grain yield and
      its components, protein content, and sedimentation value were examined at Zagreb.
      Germination, winterhardiness and grain yield were determined at Hutchinson.At
      Zagreb, the F1 hybrid exhibited significant heterosis in grain yield, even though
      two of the three yield components were intermediate to parent values. Heterotic
      effects were greater in the stress environment (Hutchinson), mainly due to the
      poor winterhardiness and lower yield of one parent variety. At Zagreb, grain
      yield of the f1 hybrid was significantly better than the best F7 line. However at
      Hutchinson, the two leading F7 Unes outyielded the f1 hybrid, but differences
      were not significant.It can be concluded that genes involved in heterosis in the
      hybrid, 'Zlatna Dolina' x 'Primepi', were not fixed in the homozygous lines
      selected from the same cross. 

PMID- 24301287
TI  - Aminoacid profiles in the study of phylogenetic relationships in the genusOryza.
AB  - The amino acid profiles in seeds of thirteen different species ofOryza, including
      two cultivated rices,O. glaberrima andO. sativa and the two major geographical
      racesindica andjaponica were studied using an automatic amino acid analyser to
      assess differences in the profiles of cultivated species and their wild
      progenitors. The polygon graphic method was employed to envision the species
      relationship. Essential amino acid profiles in different species were also
      compared with those of the Food and Agriculture Organization (FAO) standards. The
      results suggest a wide range of variability amongOryza species for lysine (up to
      4.4% as against 3.5% in cultivated rices) and other essential amino acids. This
      will be of considerable interest to rice breeders, when after overcoming genetic
      barriers, the possible utilization of these species in rice breeding becomes
      feasible. 

PMID- 24301288
TI  - Cytophotometrical measurement of nuclear DNA content in some coniferous and
      deciduous trees.
AB  - The DNA content of nuclei from meristematic root tip cells of five coniferous and
      one deciduous tree species and, for comparison, ofVicia faba was
      cytophotometrically determined. The DNA values of diploid nuclei fromGinkgo
      biloba are approximately a quarter lower than those fromVicia faba. The nuclear
      DNA values of the other tree species are merely a third to a ninth part of those
      ofVicia faba. In three tree species, as well as diploid, we have found nuclei of
      different polyploid level.The reliability of different cytochemical methods,
      which are used for determination of the nuclear DNA content, is critically
      analyzed. The DNA values of the investigated tree species are discussed in
      connection with the evolution of the DNA content in higher plants. 

PMID- 24301289
TI  - Lesion development and reperfusion benefit in relation to vascular occlusion
      patterns after embolic stroke in rats.
AB  - Vascular occlusion sites largely determine the pattern of cerebral tissue damage
      and likelihood of subsequent reperfusion after acute ischemic stroke. We aimed to
      elucidate relationships between flow obstruction in segments of the internal
      carotid artery (ICA) and middle cerebral artery (MCA), and (1) profiles of acute
      ischemic lesions and (2) probability of subsequent beneficial reperfusion.
      Embolic stroke was induced by unilateral intracarotid blood clot injection in
      normotensive (n=53) or spontaneously hypertensive (n=20) rats, followed within 2 
      hours by magnetic resonance (MR) angiography (MRA), diffusion- (DWI) and
      perfusion-weighted magnetic resonance imaging (MRI) (PWI). In a subset of animals
      (n=9), MRI was repeated after 24 and 168  hours to determine the predictive value
      of the occlusion pattern on benefit of reperfusion. The extent of cerebral
      perfusion and diffusion abnormality was related to the pattern of flow
      obstruction in ICA and MCA segments. Hypertensive animals displayed significantly
      larger cortical perfusion lesions. Acute perfusion-diffusion lesion mismatches
      were detected in all animals that subsequently benefitted from reperfusion. Yet,
      the presence of an angiography-diffusion mismatch was more specific in predicting
      reperfusion benefit. Combination of DWI, PWI, and MRA exclusively informs on the
      impact of arterial occlusion profiles after acute ischemic stroke, which may
      improve prognostication and subsequent treatment decisions.

PMID- 24301290
TI  - Impact of particulate matter exposition on the risk of ischemic stroke:
      epidemiologic evidence and putative mechanisms.
AB  - Ambient particulate matter (PM) pollution is estimated to be responsible for 3.2
      million deaths annually worldwide. Although many studies have demonstrated PM as
      a serious risk factor for cardiovascular diseases, less is known on its
      association with cerebrovascular events. Over the last decade, however, an
      increasing number of studies have provided data showing a relationship between PM
      exposure and ischemic stroke (IS). In this article, we will report on existing
      epidemiologic findings for an association between PM exposure and IS based on a
      systemic literature search. Thus, despite inconsistencies in the results,
      currently available data suggest that PM exposure is a risk factor for IS,
      especially in patients with preexisting illnesses. With regards to the mechanisms
      leading to PM-dependent vascular damage, in particular proinflammatory,
      prooxidative, as well as proatherogenic pathways have been suggested to be
      involved. Notably, to date there is only one study published, which demonstrates
      the influence of PM exposure on cerebrovascular function. We will discuss
      reasonable approaches for future neurovascular research in this field. 

PMID- 24301291
TI  - A new role for downstream Toll-like receptor signaling in mediating immediate
      early gene expression during focal cerebral ischemia.
AB  - To better understand the role of downstream Toll-like receptor (TLR) signaling
      during acute cerebral ischemia, we performed cDNA microarrays, on brain RNA, and
      cytokine arrays, on serum, from wild type (WT), MyD88-/- and TRIF-mutant mice, at
      baseline and following permanent middle cerebral artery occlusion (pMCAO). The
      acute stress response pathway was among the top pathways identified by Ingenuity
      Pathway Analysis of microarray data. We used real-time polymerase chain reaction
      to confirm the expression of four immediate early genes; EGR1, EGR2, ARC, Nurr77,
      in this pathway, and insulin degrading enzyme (IDE). Compared to WT, baseline
      immediate early gene expression was increased up to10-fold in MyD88-/- and TRIF
      mutant mice. However, following pMCAO, immediate early gene expression remained
      unchanged, from this elevated baseline in these mice, but increased up to 12-fold
      in WT. Furthermore, expression of IDE, which also degrades beta-amyloid,
      decreased significantly only in TRIF-mutant mice. Finally, sE-Selectin, sICAM,
      sVCAM-1, and MMP-9 levels were significantly decreased only in MyD88-/- compared
      with WT mice. We thus report a new role for downstream TLR signaling in immediate
      early gene expression during acute cerebral ischemia. We also show that the TRIF
      pathway regulates IDE expression; a major enzyme that clears beta-amyloid from
      the brain. 

PMID- 24301292
TI  - Monitoring cerebral oxygenation during balloon occlusion with multichannel NIRS.
AB  - We report on oxygenation changes noninvasively recorded by multichannel
      continuous-wave near infrared spectroscopy (CW-NIRS) during endovascular
      neuroradiologic interventions requiring temporary balloon occlusion of arteries
      supplying the cerebral circulation. Digital subtraction angiography (DSA)
      provides reference data on the site, timing, and effectiveness of the flow
      stagnation as well as on the amount and direction of collateral circulation. This
      setting allows us to relate CW-NIRS findings to brain specific perfusion changes.
      We focused our analysis on the transition from normal perfusion to vessel
      occlusion, i.e., before hypoxia becomes clinically apparent. The localization of
      the maximal response correlated either with the core (occlusion of the middle
      cerebral artery) or with the watershed areas (occlusion of the internal carotid
      artery) of the respective vascular territories. In one patient with clinically
      and angiographically confirmed insufficient collateral flow during carotid artery
      occlusion, the total hemoglobin concentration became significantly asymmetric,
      with decreased values in the ipsilateral watershed area and contralaterally
      increased values. Multichannel CW-NIRS monitoring might serve as an objective and
      early predictive marker of critical perfusion changes during interventions-to
      prevent hypoxic damage of the brain. It also might provide valuable human
      reference data on oxygenation changes as they typically occur during acute
      stroke. 

PMID- 24301293
TI  - Hypothalamic astroglial connexins are required for brain glucose sensing-induced
      insulin secretion.
AB  - Hypothalamic glucose detection participates in maintaining glycemic balance, food
      intake, and thermogenesis. Although hypothalamic neurons are the executive cells
      involved in these responses, there is increasing evidence that astrocytes
      participate in glucose sensing (GS); however, it is unknown whether astroglial
      networking is required for glucose sensitivity. Astroglial connexins 30 and 43
      (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions,
      allowing for the intercellular transfer of small molecules such as glucose
      throughout the astroglial networks. Here, we hypothesized that hypothalamic
      glucose sensitivity requires these connexins. First, we showed that both Cxs are
      enriched in the rat hypothalamus, with highly concentrated Cx43 expression around
      blood vessels of the mediobasal hypothalamus (MBH). Both fasting and high
      glycemic levels rapidly altered the protein levels of MBH astroglial connexins,
      suggesting cross talk within the MBH between glycemic status and the connexins'
      ability to dispatch glucose. Finally, the inhibition of MBH Cx43 (by transient
      RNA interference) attenuated hypothalamic glucose sensitivity in rats, which was
      demonstrated by a pronounced decreased insulin secretion in response to a brain
      glucose challenge. These results illustrate that astroglial connexins contribute
      to hypothalamic GS. 

PMID- 24301294
TI  - Changes in cerebral blood flow during steady-state cycling exercise: a study
      using oxygen-15-labeled water with PET.
AB  - Cerebral blood flow (CBF) during dynamic exercise has never been examined
      quantitatively using positron emission tomography (PET). This study investigated
      changes in CBF that occur over the course of a moderate, steady-state cycling
      exercise. Global and regional CBF (gCBF and rCBF, respectively) were measured
      using oxygen-15-labeled water (H(2)(15)O) and PET in 10 healthy human subjects at
      rest (Rest), at the onset of exercise (Ex1) and at a later phase in the exercise
      (Ex2). At Ex1, gCBF was significantly (P<0.01) higher (27.9%) than at Rest, and
      rCBF was significantly higher than at Rest in the sensorimotor cortex for the
      bilateral legs (M1(Leg) and S1(Leg)), supplementary motor area (SMA), cerebellar
      vermis, cerebellar hemispheres, and left insular cortex, with relative increases
      ranging from 37.6% to 70.5%. At Ex2, gCBF did not differ from Rest, and rCBF was
      significantly higher (25.9% to 39.7%) than at Rest in only the M1(Leg), S1(Leg),
      and vermis. The areas showing increased rCBF at Ex1 were consistent with the
      central command network and the anatomic pathway for interoceptive stimuli. Our
      results suggest that CBF increases at Ex1 in parallel with cardiovascular
      responses then recovers to the resting level as the steady-state exercise
      continues.

PMID- 24301295
TI  - Bone marrow-derived endothelial progenitor cells protect postischemic axons after
      traumatic brain injury.
AB  - White matter sparing after traumatic brain injury (TBI) is an important predictor
      of survival and outcome. Blood vessels and axons are intimately associated
      anatomically and developmentally. Neural input is required for appropriate
      vascular patterning, and vascular signaling is important for neuron development
      and axon growth. Owing to this codependence between endothelial cells and axons
      during development and the contribution of endothelial progenitor cells (EPCs) in
      ischemic injury, we hypothesized that EPCs are important in axonal survival after
      TBI. We examined the effects of allogenic-cultured EPCs on white matter
      protection and microvascular maintenance after midline fluid percussion injury in
      adult Sprague-Dawley rats. We used two in vitro models of injury, mechanical
      stretch and oxygen-glucose deprivation (OGD), to examine the effects of EPCs on
      the mechanical and ischemic components of brain trauma, respectively. Our results
      indicate that EPCs improve the white matter integrity and decrease capillary
      breakdown after injury. Cultured cortical neurons exposed to OGD had less axon
      degeneration when treated with EPC-conditioned media, whereas no effect was seen
      in axons injured by mechanical stretch. The results indicate that EPCs are
      important for the protection of the white matter after trauma and represent a
      potential avenue for therapy. 

PMID- 24301296
TI  - Characterization of the ubiquitin-modified proteome regulated by transient
      forebrain ischemia.
AB  - Ubiquitylation is a posttranslational protein modification that modulates various
      cellular processes of key significance, including protein degradation and DNA
      damage repair. In animals subjected to transient cerebral ischemia, ubiquitin
      conjugated proteins accumulate in Triton-insoluble aggregates. Although this
      process is widely considered to modulate the fate of postischemic neurons, few
      attempts have been made to characterize the ubiquitin-modified proteome in these
      aggregates. We performed proteomics analyses to identify ubiquitylated proteins
      in postischemic aggregates. Mice were subjected to 10 minutes of forebrain
      ischemia and 4 hours of reperfusion. The hippocampi were dissected, aggregates
      were isolated, and trypsin-digested after spiking with GG-BSA as internal
      standard. K-E-GG-containing peptides were immunoprecipitated and analyzed by
      label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS)
      analysis. We identified 1,664 peptides to 520 proteins containing at least one K
      E-GG. Sixty-six proteins were highly ubiquitylated, with 10 or more K-E-GG
      peptides. Based on selection criteria of greater than fivefold increase and
      P<0.001, 763 peptides to 272 proteins were highly enriched in postischemic
      aggregates. These included proteins involved in important neuronal functions and
      signaling pathways that are impaired after ischemia. Results of this study could
      serve as an important platform to uncover the mechanisms linking insoluble
      ubiquitin aggregates to the functions of postischemic neurons.

PMID- 24301297
TI  - Delayed progesterone treatment reduces brain infarction and improves functional
      outcomes after ischemic stroke: a time-window study in middle-aged rats.
AB  - We evaluated the neuroprotective effects of delayed progesterone (PROG) treatment
      against ischemic stroke-induced neuronal death, inflammation, and functional
      deficits. We induced transient focal cerebral ischemia in male rats and
      administered PROG (8 mg/kg) or vehicle intraperitoneally at 3, 6, or 24 hours
      post occlusion, subcutaneously 5 hours later and then every 24 hours for 7 days.
      Behavioral outcomes were evaluated over 22 days. Infarct size and other
      biomarkers of injury were evaluated by cresyl violet staining, and matrix
      metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP), and vascular
      endothelial growth factor (VEGF) by immunofluorescence. Progesterone treatment
      started at 3 and 6 hours post occlusion significantly (P<0.05) improved
      behavioral performance at all time points (74.01%) and reduced infarction volume
      (61.68%) compared with vehicle. No significant difference was observed between
      the 3 and 6 hour PROG treatment groups. Matrix metalloproteinase-9 and VEGF were
      upregulated in the PROG groups compared with vehicle. Glial fibrillary acidic
      protein expression was increased in the vehicle group but markedly lower in the
      PROG groups. Treatment delayed for 24 hours did not significantly improve
      functional outcomes or reduce infarction volume. We conclude that, under the
      right treatment conditions, PROG treatment delayed up to 6 hours can improve
      functional deficits and reduce brain infarction, possibly by modulating GFAP,
      VEGF, and MMP-9 expression. 

PMID- 24301299
TI  - A photo-induced C-O bond formation methodology to construct tetrahydroxanthones.
AB  - A metal-free, photo-induced C-O bond formation methodology was developed to
      construct tetrahydroxanthones. This mild and efficient methodology was based on
      intramolecular oxygen trapping of the reactive species produced by photolytic
      activation of a C-Cl bond. We believe this method could be used in the synthesis
      of related xanthone-type natural products. 

PMID- 24301298
TI  - Upregulation of SYF2 is associated with neuronal apoptosis caused by reactive
      astrogliosis to neuroinflammation.
AB  - SYF2, known as CCNDBP1-interactor or p29, is likely involved in pre-mRNA splicing
      and cell cycle progression. The present study was designed to elucidate dynamic
      changes in SYF2 expression and distribution in the cerebral cortex in a
      lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that
      SYF2 expression was induced strongly in active astrocytes after LPS injection. In
      vitro studies showed that the upregulation of SYF2 might be involved in the
      activation of C6 cells after LPS challenge and the neuronal apoptosis after
      conditioned media challenge. In addition, with silencing of SYF2 in C6 and PC12
      cells by siRNA, the results indicated that SYF2 was required for astrocyte
      activation and neuronal apoptosis induced by LPS. Our findings on the cellular
      signaling pathway may provide a new therapeutic strategy against
      neuroinflammation in the CNS.

PMID- 24301300
TI  - NCI group urges the medical community to address the increasing problem of cancer
      overdiagnosis and overtreatment.

PMID- 24301301
TI  - Young brain cancer patient inspires drug discovery project.

PMID- 24301302
TI  - Poor oral health tied to oral HPV infection.

PMID- 24301303
TI  - Histone modification patterns correlate with patient outcome in oral squamous
      cell carcinoma.
AB  - BACKGROUND: Patterns of global histone modifications have been suggested to be
      predictors of clinical outcome in many cancers. However, the role of global
      histone modification patterns in oral squamous cell carcinoma (OSCC) is unclear.
      METHODS: A retrospective clinicopathologic analysis was undertaken of 186
      patients with oral squamous cell carcinoma who received complete ablative
      surgical treatment. Tissue arrays were made from those paraffin-embedded OSCC
      samples and examined by immunohistochemistry for histone 3 lysine 4 acetylation
      (H3K4ac), histone 3 lysine 18 acetylation (H3K18ac), histone 3 lysine 4
      trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and
      histone 3 lysine 27 trimethylation (H3K27me3). RESULTS: A low level of H3K4ac and
      a high level of H3K27me3 were associated with advanced T status, N status, tumor
      stage, and perineural invasion. They were also correlated with cancer-specific
      survival (CSS) and disease-free survival (DFS). The 5-year CSS and DFS in
      H3K4ac(low) vs. H3K4ac(high) were 74.8% versus 92.5% (P = .010), and 51.4% versus
      76.2% (P = .001), respectively. The 5-year CSS and DFS in H3K27me3(low) versus
      H3K27me3(high) were 94.7% versus 62.3% (P < .001) and 76.4% versus 32.3% (P <
      .001), respectively. We also found improved prediction for DFS after combining
      the H3K4ac(low) and H3K27me3(high) profiles and comparing the scores with the
      other modification patterns (P < .0001). CONCLUSIONS: This research demonstrates
      the potential prognostic utility of global histone modification analysis for
      OSCC.

PMID- 24301304
TI  - MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent
      papillary thyroid cancer.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) persistence or recurrence and the need
      for long-term surveillance can cause significant inconvenience and morbidity in
      patients. Currently, recurrence risk stratification is accomplished by using
      clinicopathologic factors, and serum thyroglobulin is the only commercially
      available marker for persistent or recurrent disease. The objective of this study
      was to determine microRNA (miRNA) expression in PTC and determine whether 1 or
      more miRNAs could be measured in plasma as a biomarker for recurrence. METHODS:
      Patients with recurrent PTC (Rc-PTC) and those without recurrence (NR-PTC) were
      retrospectively recruited for a comparison of their tumor miRNA profiles.
      Patients with either newly diagnosed PTC or multinodular goiter who were
      undergoing total thyroidectomy were prospectively recruited for an analysis of
      preoperative and postoperative circulating miRNA levels. Healthy volunteers were
      recruited as the control group. RESULTS: MicroRNA-222 and miR-146b were over
      expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR
      PTC tumors (P = .014 and P = .038, respectively). In plasma from preoperative PTC
      patients, levels of miR-222 and miR-146b were higher compared with the levels in
      plasma from healthy volunteers (P < .01 for both). Reductions of 2.7-fold and 5.1
      fold were observed in the plasma levels of miR-222 and miR-146b, respectively,
      after total thyroidectomy (P = .03 for both). CONCLUSIONS: This study
      demonstrated that tumor levels of miR-222 and miR-146b are associated with PTC
      recurrence and that miR-222 and miR-146b levels in the circulation correspond to
      the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve
      patient stratification according to the risk of recurrence and as circulating
      biomarkers for PTC surveillance warrants further study.

PMID- 24301306
TI  - Segregation of genes transferred to one plant cell from two separate
      Agrobacterium strains.
AB  - Agrobacterium tumefaciens and Agrobacterium rhizogenes are soil bacteria which
      transfer DNA (T-DNA) to plant cells. Two Agrobacterium strains, each with a
      different T-DNA, can infect plants and give rise to transformed tissue which has
      markers from both T-DNAs. Although marker genes from both T-DNAs are in the
      tissue, definitive proof that the tissue is a cellular clone and that both T-DNAs
      are in a single cell is necessary to demonstrate cotransformation. We have
      transferred two distinguishable T-DNAs, carried on binary vectors in separate
      Agrobacterium rhizogenes strains, into tomato cells and have recovered hairy
      roots which received both T-DNAs. Continued expression of marker genes from each
      T-DNA in hairy roots propagated from individual root tips indicated that both T
      DNAs were present in a single meristem. Also, we have transferred the two
      different T-DNAs, carried on identical binary vector plasmids in separate
      Agrobacterium tumefaciens strains, into tobacco cells and recovered plants which
      received both T-DNAs. Transformed plants with marker genes from each T-DNA were
      outcrossed to wild-type tobacco plants. Distribution of the markers in the F1
      generation from three cotransformed plants of independent origin showed that both
      T-DNAs in the plants must have been present in the same cell and that the T-DNAs
      were genetically unlinked. Cotransformation of plant cells with T-DNAs from two
      bacterial strains and subsequent segregation of the transferred genes should be
      useful for altering the genetic content of higher plants. 

PMID- 24301307
TI  - Multiple host-specificity loci of the broad host-range Rhizobium sp. NGR234
      selected using the widely compatible legume Vigna unguiculata.
AB  - Specificity in legume-Rhizobium symbiosis depends on plant and rhizobial genes.
      As our objective was to study broad host-range determinants of rhizobia, we
      sought a legume and a Rhizobium with the lowest possible specificity. By
      inoculating 12 different legumes with a heterogenous collection of 35 fast
      growing rhizobia, we found Rhizobium sp. NGR234 to be the Rhizobium and Vigna
      unguiculata to be the plant with the lowest specificities. Transfer of cloned
      fragments of the Sym-plasmid pNGR234a into heterologous rhizobia, screening for
      extension of host-range of the transconjugants to include V. unguiculata, and
      restriction mapping of the Hsn- and overlapping clones, proved that there were at
      least three distinct Hsn-regions (HsnI, II, and III) on pNGR234a. HsnI is located
      next to nodD, HsnII is linked to nifKDH and HsnIII to nodC. In addition to
      nodulation of Vigna, HsnI conferred upon the transconjugants the ability to
      nodulate Glycine max, Macroptilium atropurpureum and Psophocarpus tetragonolobus.
      All three Hsn-regions, when transferred to the appropriate recipients, induced
      root-hair-curling on M. atropurpureum. Hsn-region III was able to complement a
      mutation in the host-range gene nodH of R. meliloti strain 2011. Homology to "nod
      box"-sequences could be shown only for the sub-clones containing HsnII and
      HsnIII, thus suggesting different regulation mechanisms for HsnI and HsnII/III. 

PMID- 24301308
TI  - Transformation of the forage legume Trifolium repens L. using binary
      Agrobacterium vectors.
AB  - A system was established for introducing cloned genes into white clover
      (Trifolium repens L.). A high regeneration white clover genotype was transformed
      with binary Agrobacterium vectors containing a chimaeric gene which confers
      kanamycin resistance. Transformed kanamycin resistant callus was obtained by
      culturing Agrobacterium inoculated stolon internode segments on selective medium.
      The kanamycin resistance phenotype was stable in cells and in regenerated shoots.
      Transformation was confirmed by the expression of an unselected gene, nopaline
      synthase in selected cells and transgenic shoots and by the detection of neomycin
      phosphotransferase II enzymatic activity in kanamycin resistant cells.
      Integration of vector DNA sequences into plant DNA was demonstrated by Southern
      blot hybridisation. 

PMID- 24301309
TI  - Nucleic acid (cDNA) and amino acid sequences of isocitrate lyase from castor
      bean.
AB  - A cDNA library was constructed to mRNA enriched for isocitrate-lyase mRNA from
      castor-bean (Ricinus communis var. zanzibarensis) endosperms. Nine clones for
      isocitrate lyase (EC 4.1.3.1) were identified. The insert of 2.2 kb from clone
      ICL4 was sequenced and proved to contain the entire coding region, 1731 bp, for
      isocitrate lyase. The amino acid sequence of isocitrate lyase was deduced from
      the nucleic acid sequence. By analogy with muscle aldolase a lysine residue that
      possibly takes part in the binding of the substrate was identified. The 3'
      untranslated region contained three putative polyadenylation addition signals and
      two direct repeats. 

PMID- 24301310
TI  - Independent encapsidation of tomato golden mosaic virus A component DNA in
      transgenic plants.
AB  - Tomato golden mosaic virus (TGMV), a member of the geminivirus group, has a
      genome consisting of two DNA molecules designated the A and B components. Both
      are required for infectivity in healthy plants, although the former has been
      shown to replicate independently in transgenic plants containing tandem direct
      repeats of the A genome component. In the studies presented here, petunia plants
      transgenic for either both components (A*B hybrids) or the A component alone were
      examined for the presence of virus particles and encapsidated, single stranded
      viral DNA. The results of DNase protection experiments and direct observation of
      extracts from transgenic plants by electron microscopy indicate that single
      stranded TGMV DNA is in both cases packaged into paired particles identical to
      those obtained from virus-infected plants. DNase-treated virions isolated from
      A*B hybrid petunia are infectious when inoculated onto healthy Nicotiana
      benthamiana. Likewise, virions obtained from transgenic A petunia are infectious
      for plants transgenic for the B component.Our observations of TGMV replication in
      transgenic plants indicate that TGMV A DNA encodes all viral functions necessary
      for the replication and encapsidation of viral DNA. The possible role of the B
      component in TGMV replication is discussed. 

PMID- 24301311
TI  - Cloning of cDNA for phytochrome from etiolated Cucurbita and coordinate
      photoregulation of the abundance of two distinct phytochrome transcripts.
AB  - We have isolated several cDNA clones for phytochrome from a dicot, Cucurbita pepo
      L. cv. Black Beauty (zucchini), and have used them to study the regulation of
      Cucurbita phytochrome mRNA levels. A cDNA library was constructed from poly(A)(+)
      RNA isolated from etiolated Cucurbita hypocotyl hooks and enriched for
      phytochrome mRNA by size fractionation. This library was screened with a (32)P
      labeled fragment isolated from an Avena phytochrome cDNA clone. Several putative
      phytochrome clones were isolated and mapped by restriction endonuclease analysis.
      On the basis of this analysis there is no evidence for the expression of multiple
      phytochrome genes in Cucurbita. Recent sequence analysis has confirmed that the
      largest of these clones, pFMD1 (~3.6 kb), does indeed encode phytochrome and that
      it contains the entire amino acid coding sequence for Cucurbita phytochrome (33).
      RNA blot analysis has revealed that two polyadenylated phytochrome transcripts
      (~5.6 kb and ~4.2 kb) are present in both cotyledons and hypocotyl hooks of
      Cucurbita. In etiolated Cucurbita seedlings given a saturating pulse of red
      light, the abundance of both transcripts coordinately declines to 50-60% of the
      dark levels within 3 h and reaccumulates to dark levels within 24 h. Reversal of
      induction of this response by a far-red light pulse immediately following red
      light treatment is not observed, which is in contrast to the far-red
      reversibility of the red light promoted decrease in phytochrome mRNA abundance
      observed in Avena (6). Etiolated seedlings transferred to continuous white light
      also show a coordinate decrease in the levels of the two RNAs to ~40% of the dark
      levels within 3 h. The magnitude of the light-induced decline in phytochrome mRNA
      abundance in Cucurbita is substantially less than the decrease previously
      reported for Avena (6). 

PMID- 24301312
TI  - Characterization of repetitive elements in several Cucurbita species.
AB  - About 1.3*10(5) copies of a tandemly arranged, 351 base pair element constitute
      from 4 to 8% of the Cucurbita pepo genome. A homologous, high copy number
      repetitive element is present in the genomes of C. moschata and C. foetidissima,
      but not in C. maxima or Cucumis sativus. Array lengths of at least 65 members
      have been detected for C. pepo, and 140 for C. moschata. The nucleotide sequence
      of six C. pepo repeat units were determined and each was found to be unique,
      differing from the others at from 7 to 23 positions. The element was composed of
      highly modified DNA as evidenced by the fact that only one of its two Hpa I
      restriction sites is subject to digestion and by the observation that all
      internal Cs and about half of the external Cs of its single Hpa II site are
      methylated. At least 5 cellular RNA species contain sequences complementary to
      one of the DNA strands of the element. These have discrete sizes of 3.0, 2.3,
      1.8, 1.3 and 0.5 kb. Such transcripts are detected in C. pepo, C. moschata and C.
      foetidissima stem and/or leaf RNA, but not root RNA and are probably not
      polyadenylated. No transcripts were found which contain sequences complementary
      to the other DNA strand of the element. 

PMID- 24301313
TI  - Analysis of mitochondrial DNA from somatic hybrid cell lines of Saccharum
      officinarum (sugarcane) and Pennisetum americanum (pearl millet).
AB  - Mitochondrial DNA (mtDNA) from cell suspension cultures of two intergeneric
      somatic hybrids of Pennisetum americanum (pearl millet) + Saccharum officinarum
      (sugarcane) was examined by restriction endonuclease digestion and hybridization
      with sorghum mtDNA cosmids. The mtDNA of one somatic hybrid was indistinguishable
      from that of pearl millet, while the second exhibited a combination of parental
      mtDNAs, suggesting mitochondrial fusion. Several novel, possibly recombinant,
      mtDNA restriction fragments were detected in this hybrid, which may have resulted
      from intergenmic recombination. 

PMID- 24301314
TI  - APC/C-Cdh1 coordinates neurogenesis and cortical size during development.
AB  - The morphology of the adult brain is the result of a delicate balance between
      neural progenitor proliferation and the initiation of neurogenesis in the
      embryonic period. Here we assessed whether the anaphase-promoting
      complex/cyclosome (APC/C) cofactor, Cdh1--which regulates mitosis exit and G1
      phase length in dividing cells--regulates neurogenesis in vivo. We use an embryo
      restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1
      ubiquitin ligase activity is required for both terminal differentiation of
      cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of
      Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of
      the progenitor cells from the cell cycle. This causes replicative stress and p53
      mediated apoptotic death resulting in decreased number of cortical neurons and
      cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical
      neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of
      congenital neurodevelopmental disorders, such as microcephaly.

PMID- 24301315
TI  - Reactivity of three-coordinate iron-NHC complexes towards phenylselenol and
      lithium phenylselenide.
AB  - The three-coordinate iron(II) NHC complexes [(IPr)Fe(N'')2] (1) and
      [(I(t)Bu)Fe(N'')2] (3) (N'' = N(SiMe3)2) react with PhSeH or LiSePh to give the
      iron(II) selenolates [(IPr)Fe(N'')(SePh)] (6) and
      [I(t)Bu(H)][(aI(t)Bu)Fe(SePh)3], [I(t)Bu(H)][7], with complex 7 containing an
      abnormal NHC ligand.

PMID- 24301316
TI  - Perceptions of child rearing and self-concept development during the early
      adolescent years.
AB  - In order to investigate the relationship between aspects of child rearing and
      adolescent self-concept, 130 males and females in grades 7, 8, and 9 completed
      Schaefer's Children's Report of Parental BehaviorInventory (CRPBI) and
      Coopersmith's Self-Esteem Inventory. Correlations between the
      Acceptance/Rejection dimension of the CRPBI and the various self-esteem subscores
      were positive. Correlations between the self-esteem scores and the Psychological
      Autonomy/Psychological Control dimension of the CRPBI were negative. The
      correlations were stronger for perceptions of mothers' as opposed to fathers'
      child-rearing practices. Analyses of variance indicated that ninth-graders
      perceived their parents as less accepting than seventhor eighth-graders. High
      self-esteem adolescents perceived their parents as more accepting, as using less
      psychological control, and as not being overly firm in making and enforcing rules
      and regulating the adolescents' behavior. The results support the contention that
      optimal self-concept development takes place in an atmosphere of acceptance that
      allows the adolescent autonomy and the opportunity to learn competencies. 

PMID- 24301317
TI  - Social orientation and the social self-esteem of gifted and talented female
      adolescents.
AB  - Carlson's developmental theory of self-concept provides a theoretical explanation
      for equivalent levels of self-esteem among both sexes, despite sex differences in
      self-concept. The present study tests the applicability of Carlson's theory for a
      sample of gifted and talented female adolescents by examining three dimensions of
      possible self-esteem antecedents: actual talent ratings, self-perceptions of
      talent, and personality attributes. According to Carlson, talent ratings, self
      perceptions, and personality attributes consistent with the feminine gender-role
      stereotype and a social orientation should emerge as positive predictors of the
      female adolescent's social self-esteem. Results of the regression analyses
      indicate that the best prediction of the social self-esteem of gifted and
      talented female adolescents is obtained from a combination of stereotypic
      feminine socially oriented and stereotypic masculine personally oriented
      predictor variables. For this sample, constructs such as androgyny appear to be
      more relevant to the understanding of social self-esteem than dichotomies such as
      personal-social orientation. 

PMID- 24301318
TI  - Self-concept of adolescent sexual abuse victims.
AB  - To assess the self-concept and psychological profile associated with sexual
      abuse, 20 young female victims evaluated in a sexual abuse clinic completed the
      Offer Self-Image Questionnaire (OSIQ). The alleged assault was intrafamilial in
      13 cases, lasting from several months to 10 years. Extrafamilial abuses were
      isolated events. Intercourse was alleged in 18 of the 20 instances. OSIQ group
      mean scores were in the poorly adjusted range for three scales, indicating
      serious problems with sexual attitudes, family relations, and feelings of
      inability to master the external environment. While the mean Overall Adjustment
      scale score was within normal limits, 10 girls had scores in the range indicating
      severe problems in adjustment; 7 were incest victims. Compared to nonsexually
      abused adolescent patients from a general adolescent clinic, sexually abused
      youth had significantly more problems with vocational/educational goals,
      psychopathology, and ability to master the environment (p<0.05). The self-concept
      problems identified in these sexually abused youth (a) are similar to those
      reported by women seeking psychiatric care long after their childhood sexual
      abuse occurred and (b) share some features reported among physically abused
      adolescents. 

PMID- 24301319
TI  - What's different about truants? A comparison study of eighth-graders.
AB  - Differences and similarities between 25 eighth-grade truants and 25 nontruants
      matched for age, grade, gender, and ethnicity-were explored on four dimensions:
      family variables, friendship patterns and interests, behavior and attitudes
      toward school, and cognitive factors including academic ability and achievement.
      The major differences were in school behavior, attitudes, academic ability, and
      achievement. The most frequent reasons given for truancy were boredom and dislike
      of school and teachers. Truancy was associated with highly disruptive classroom
      behavior. The salience of school variables suggests that truancy prevention and
      intervention strategies should include improved course content, teaching, and
      school climate. The necessity of having a comparison group is stressed in order
      to distinguish characteristics of normal adolescent development from those
      associated with maladjustment. 

PMID- 24301320
TI  - Sex differences in the causes of adolescent suicide ideation.
AB  - A model that incorporates both socioenvironmental and psychological factors was
      developed in an attempt to explain adolescent suicide ideation. A sample of 407
      high school students was used to test the model. Most of the previous research on
      the causes of adolescent suicidal behavior has not used multivariate data
      analysis techniques and has failed to explore sex differences. Results of the
      present study suggest that these are important omissions. Although significant at
      the zero-order level, factors such as self-esteem and interpersonal problems at
      school were not related to suicide ideation when the effects of the other
      explanatory variables were controlled. The incidence of suicide ideation was
      higher for females. Emotional problems and involvement in delinquent behavior
      were important predictors of ideation for females, while employment problems were
      the most potent predictor for males. 

PMID- 24301321
TI  - Cognitive mediators of ego functioning in adolescence.
AB  - It has often been assumed that a relationship exists between higher levels of
      cognitive functioning, particularly formal operations, and mature ego functioning
      in adolescence. This research examined the relationships between ego functioning
      and two domains of operational thinking: social interpersonal reasoning and
      physical-mathematical reasoning in 139 high school seniors. Subjects were given
      two measures of physical-mathematical reasoning, two measures of interpersonal
      reasoning, and the Sentence Completion Test of ego functioning, as well as a
      measure of verbal intelligence. Results indicated significant differences between
      males and females in patterns of correlations as well as in patterns of
      relationships in a causal analysis. Ego functioning was predicted by
      interpersonal reasoning for females and by physical-mathematical reasoning and
      verbal intelligence for males. 

PMID- 24301322
TI  - BitCoin meets Google Trends and Wikipedia: quantifying the relationship between
      phenomena of the Internet era.
AB  - Digital currencies have emerged as a new fascinating phenomenon in the financial
      markets. Recent events on the most popular of the digital currencies--BitCoin-
      have risen crucial questions about behavior of its exchange rates and they offer
      a field to study dynamics of the market which consists practically only of
      speculative traders with no fundamentalists as there is no fundamental value to
      the currency. In the paper, we connect two phenomena of the latest years--digital
      currencies, namely BitCoin, and search queries on Google Trends and Wikipedia-
      and study their relationship. We show that not only are the search queries and
      the prices connected but there also exists a pronounced asymmetry between the
      effect of an increased interest in the currency while being above or below its
      trend value.

PMID- 24301323
TI  - The new licencing examination for human medicine: from concept to implementation.
AB  - A new Swiss federal licencing examination for human medicine (FLE) was developed
      and released in 2011. This paper describes the process from concept design to the
      first results obtained on implementation of the new examination. The development
      process was based on the Federal Act on University Medical Professions and
      involved all national stakeholders in this venture. During this process questions
      relating to the assessment aims, the assessment formats, the assessment
      dimensions, the examination content and necessary trade-offs were clarified. The
      aims were to create a feasible, fair, valid and psychometrically sound
      examination in accordance with international standards, thereby indicating the
      expected knowledge and skills level at the end of undergraduate medical
      education. Finally, a centrally managed and locally administered examination
      comprising a written multiple-choice element and a practical "clinical skills"
      test in the objective structured clinical examination (OSCE) format was
      developed. The first two administrations of the new FLE show that the examination
      concept could be implemented as intended. The anticipated psychometric indices
      were achieved and the results support the validity of the examination. Possible
      changes to the format or content in the future are discussed.

PMID- 24301324
TI  - Direct oral anticoagulants and antiplatelet agents. Clinical relevance and
      options for laboratory testing.
AB  - Oral anticoagulants and platelet receptor blockers are widely used in clinical
      practice with the aim of reducing the risk of thrombotic complications in
      patients with cardiovascular diseases. Their regular intake and adequate
      antithrombotic action is vital and this is way numerous assays have been
      developed for laboratory testing and monitoring of these agents. Available assays
      can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays
      are increasingly used in clinical routine and their daily use is triggered by the
      advent of the novel direct oral anticoagulants (DOACs) as an alternative for
      vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and
      apixaban, and by the advent of prasugrel or ticagrelor as an alternative for
      clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the
      most important and most commonly used laboratory assays are summarized as well as
      their clinical implications with the focus on DOACs as an alternative for VKAs
      and the different P2Y12 receptor blockers for antiplatelet treatment. 

PMID- 24301326
TI  - Fiscal myopia or constituency building.

PMID- 24301325
TI  - Artesunate-amodiaquine combination therapy in the absence of malarial parasite
      infection induces oxidative damage in female rats.
AB  - Artesunate-amodiaquine is among the most widely available artemisinin combination
      therapy used as treatment regimen for uncomplicated Plasmodium falciparum
      malaria. Our aim was to evaluate clinical routine markers of liver and renal
      functions, lipid profile levels and lipid peroxidation status in a female
      mammalian rat model. This was an attempt to simulate a scenario where the drugs
      are taken without malarial parasite infection, which is a common practice in
      settings where drug misuse is a common practice. Twenty female Wistar rats were
      randomly divided into four study groups of five animals each. Group 1 (control)
      received distilled water, group 2 was exposed to artesunate [2 mg/kg body weight
      (b.w.)], group 3 was administered with amodiaquine (6.12 mg/kg b.w.) and group 4
      was co-administered with artesunate (2 mg/kg b.w.) and amodiaquine (6.12 mg/kg
      b.w.) for 3 days. At the end of the treatment period, animals were fasted
      overnight and sacrificed. Markers of liver and renal functions and lipid profile
      indices were evaluated in the plasma, whereas lipid peroxidation status, GSH
      concentration and G6PD activity were assessed in the erythrocytes. The results
      showed that the co-administration of artesunate and amodiaquine altered liver
      function markers and lipid profile indices. The drugs also induced lipid
      peroxidation as evidenced by the elevated level of oxidative stress marker
      malondialdehyde (p < 0.05). We recommend therefore that the drugs should be taken
      with prescription only with clinical evidence of malarial parasite infection.

PMID- 24301327
TI  - Easing the distress of grief: A selected review of the literature with
      implications for prevention programs.
AB  - This article examines the growing literature on grief and from that literature
      applies the tools of prevention (education, community organization, competency
      promotion and natural caregiving) to easing the distress surrounding this life
      event. 

PMID- 24301328
TI  - Perceptions of classroom environment and their relationship to children's mood,
      achievement, popularity and adjustment.
AB  - This study examines relationships between: (a) teacher perception and (b) student
      teacher convergence of perception of environment, and student mood, achievement,
      popularity and adjustment, for students in general and for "problem" (i.e.,
      acting-out, anxious, and unpopular) subgroups. Subjects included 511 5th and 6th
      graders, and their 23 teachers, from 4 suburban schools. A short form of the
      Classroom Environment Scale (CES) was used to assess teacher and student
      perception of the classroom. Students also completed mood adjective checklists
      and peer sociometric ratings. Reading and math report card grades and achievement
      test scores were recorded for the school year, and teachers submitted adjustment
      ratings for all students. Since students and teachers saw their classrooms
      differently, the two perspectives were studied separately. The four CES scales,
      based on teacher perceptions and student-teacher convergence that best predicted
      positive mood, peer popularity and teacher rated adjustment were Involvement,
      Order and Organization, Affiliation, and Rule Clarity. Findings were
      directionally similar for the average class and problem students, though stronger
      for the latter. 

PMID- 24301329
TI  - A health center response to community crisis: Some principles of prevention and
      intervention.
AB  - September 1975 saw implementation of Phase Two of mandatory bussing of children
      in the Boston Public Schools. This article describes the experiences of the
      neighborhood health center in Charlestown, Massachusetts prior to, during, and
      after the initial crisis period. Principles relating to prevention and
      intervention emerged which can be applied by community clinicians when they face
      potential or actual community crises. The article emphasizes health center
      efforts to intervene in the anticipatory stress which occurred prior to the onset
      of bussing. The short- and long-term effects of the crisis on the neighborhood
      and on the health center are briefly discussed. 

PMID- 24301331
TI  - The politics of prevention.

PMID- 24301330
TI  - The Community Baby Shower: Detroit packages prevention messages to teenage
      parents.

PMID- 24301332
TI  - Let a thousand flowers bloom?

PMID- 24301333
TI  - Creative controversy.

PMID- 24301334
TI  - Hollister replies.

PMID- 24301335
TI  - Primary prevention program clearinghouse Psychology Department-Dewey Hall
      University of Vermont, Burlington, VT. 05405.

PMID- 24301337
TI  - Pulmonary neuroendocrine tumors: study of 90 cases focusing on
      clinicopathological characteristics, immunophenotype, preoperative biopsy, and
      frozen section diagnoses.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary neuroendocrine tumors have a prognostic
      spectrum including typical carcinoid (TC), atypical carcinoid (AC), small cell
      carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). We conducted a
      retrospective study to compare their clinicopathological characteristics,
      immunophenotype, preoperative biopsy and frozen section diagnoses, and prognosis.
      METHODS: Ninety cases of surgically treated pulmonary neuroendocrine tumors were
      studied. Immunohistochemical studies were performed using antibodies to
      chromogranin A, synaptophysin, and CD56. The preoperative biopsy and frozen
      section diagnoses were reviewed. RESULTS: The 5-year survival rates for TC, AC,
      SCLC, and LCNEC were 96.6%, 66.7%, 42.4%, and 38.0%, respectively. T stage and
      pleural status correlated with outcome of SCLC and LCNEC, but N-stage and overall
      TNM stage did not. In preoperative biopsy, accurate diagnosis was achieved in 5
      of 11 TC, 2 of 4 AC, 6 of 15 SCLC, and 0 of 5 LCNEC cases. Using frozen sections,
      accurate diagnosis was achieved in 8 of 12 TC, 2 of 11 SCLC, and 0 of 11 LCNEC
      cases. CONCLUSIONS: LCNEC was the most difficult to diagnose using either
      preoperative biopsy or frozen sections. T stage and pleural status can predict
      outcome of SCLC and LCNEC.

PMID- 24301336
TI  - Octopus visual system: a functional MRI model for detecting neuronal electric
      currents without a blood-oxygen-level-dependent confound.
AB  - PURPOSE: Despite the efforts that have been devoted to detecting the transient
      magnetic fields generated by neuronal firing, the conclusion that a functionally
      relevant signal can be measured with MRI is still controversial. For human
      studies of neuronal current MRI (nc-MRI), the blood-oxygen-level-dependent (BOLD)
      effect remains an irresolvable confound. For tissue studies where hemoglobin is
      removed, natural sensory stimulation is not possible. This study investigates the
      feasibility of detecting a physiologically induced nc-MRI signal in vivo in a
      BOLD-free environment. METHODS: The cephalopod mollusc Octopus bimaculoides has
      vertebrate-like eyes, large optic lobes (OLs), and blood that does not contain
      hemoglobin. Visually evoked potentials were measured in the octopus retina and OL
      by electroretinogram and local field potential. nc-MRI scans were conducted at
      9.4 Tesla to capture these activities. RESULTS: Electrophysiological recording
      detected strong responses in the retina and OL in vivo; however, nc-MRI failed to
      demonstrate any statistically significant signal change with a detection
      threshold of 0.2 degrees  for phase and 0.2% for magnitude. Experiments in a
      dissected eye-OL preparation yielded similar results. CONCLUSION: These findings
      in a large hemoglobin-free nervous system suggest that sensory evoked neuronal
      magnetic fields are too weak for direct detection with current MRI technology.

PMID- 24301338
TI  - The nucleolus organizers of diploid wheats revealed by in situ hybridization.
AB  - Labelled RNA, transcribed in vitro from wheat ribosomal DNA cloned in a bacterial
      plasmid, has been hybridised to metaphase chromosomes of five diploid wheats.
      Autoradiography of the chromosomes has provided unequivocal evidence that these
      genotypes possess two pairs of nucleolus organizer chromosomes. The diploid wheat
      accessions used possess widely differing numbers of ribosomal RNA genes. 

PMID- 24301339
TI  - The inheritance of partial self-compatibility in Brassica oleracea L. inbreds
      homozygous for different S-alleles.
AB  - In a study of partial self-compatibility in Brassica oleracea, flower number,
      seeded siliqua and seed production were recorded on self and cross-pollinated
      inflorescences of 32 progenies obtained by inter-crossing and selfing 8 plants
      homozygous for the incompatibility alleles S2, S5, S15 and S45.Progeny
      differences for both self-and out-cross seed production could be largely
      attributed to G.C.A. effects which were essentially uncorrelated. For cross
      pollinated inflorescences heterosis was also important. Significant differences
      were found for selfed seed set and its two components, the proportion of flowers
      producing seeded siliquae and the numbers of seed per seeded siliqua, between
      parents with the same S-allele which could not be attributed to S-genotype alone.
      No evidence of increased self-compatibility in particular S-allele heterozygotes
      (mutual weakening) could be found.Outcross seed production depended primarily on
      the numbers of seeds set per seeded siliqua while self seed production was
      largely determined by the proportion of flowers which produced seeded siliqua. It
      is suggested that this is a key character for the production of inbred lines with
      reduced partial self-compatibility. 

PMID- 24301340
TI  - Glutenin subunits of genetically related European hexaploid wheat cultivars:
      Their relation to bread-making quality.
AB  - The subunit composition of glutenin from 47 European wheat cultivars was studied
      using SDS-polyacrylamide gel electrophoresis. These cultivars are genetically
      related since they originate from the same stock. Moreover, the diversity of
      sample, containing cultivars with very different French bread-making qualities,
      makes it possible to investigate the relationship between glutenin subunit
      composition and bread-making quality. 16 electrophoretic types of glutenin
      subunits could be distinguished: these were grouped into four classes. Depending
      on the cultivar, six to eight glutenin subunits with MW more than or equal to
      62,000 were detected. Subunits 3 and 5, with an approximate MW of 122,000 and
      108,000 respectively, seem to play a prominent role on bread-making quality; they
      were found in cultivars of good quality and were absent in those unsuitable for
      making French bread. Two other subunits (9 and 10; MW: 71,000 and 66,000,
      respectively) have a less defined influence but may be needed in some types of
      glutenin structure. Aneuploid analysis shows that in 'Chinese Spring', subunit 5
      is coded by a gene on the long arm of chromosome 1B. The location of genes coding
      for subunits 3, 9 and 10 could not be determined. 

PMID- 24301341
TI  - Control by homoeologous group 1 chromosomes of the high-molecular-weight subunits
      of glutenin, a major protein of wheat endosperm.
AB  - The electrophoretic mobilities of the high-molecular-weight (HMW) subunits of
      glutenin from 7 varieties were compared by polyacrylamide-gel electrophoresis in
      the presence of sodium dodecyl sulphate (SDS). In total, 12 subunits were clearly
      resolved and they had nominal molecular weights of between 95,000 and 140,000.
      The chromosomes which control their synthesis were determined using monosomic
      lines and inter-varietal substitution lines. All subunits were shown to be
      controlled by the homoeologous group 1 chromosomes. Each variety contains between
      3 and 5 HMW subunits; two are under the control of the 1D chromosome, 1 or 2 are
      controlled by chromosome 1B and 0 or 1 by chromosome 1A. The segregation of two
      1D-controlled subunits of similar electrophoretic mobilities were analysed in the
      F2 progeny of crosses between 'Chinese Spring' and 'Holdfast'. The results
      suggest that the genes which code for the two proteins are allelic. 

PMID- 24301342
TI  - Restoration of fertility in cytoplasmic male sterile (CMS) Nicotiana Sylvestris
      by fusion with X-irradiated N. tabacum protoplasts.
AB  - Restoration of male fertility was achieved by fusing protoplasts from male
      sterile (CMS) Nicotiana sylvestris plants with X-irradiated protoplasts derived
      from fertile N. tabacum plants. The CMS N. sylvestris plants were derived from a
      previous somatic hybridization experiment and contained alien (Line 92)
      cytoplasm. About one quarter of the regenerated plants were found to be cybrids.
      i.e. they consisted of N. sylvestris nuclei combined with all or some components
      of N. tabacum cytoplasm. In one half of these cybrids male fertility was restored
      to different levels. The chloroplasts of the two parental donors differ in
      respect to tentoxin sensitivity: chloroplasts of CMS N. sylvestris are sensitive
      while those of N. tabacum are insensitive. It could therefore be demonstrated
      that there was an independent segregation of chloroplast type and male
      fertility/sterility: several somatic cybrids were male fertile but tentoxin
      sensitive and others were tentoxin insensitive yet they were male sterile. Only
      in about one half of the somatic cybrids was male fertility restored together
      with restoration to tentoxin insensitivity. 

PMID- 24301343
TI  - Hybridization and selection for improving seed protein in barley.
AB  - Hybridization followed by continuous selection of lines of barley from different
      cross-combinations involving high protein-high lysine genotypes and the
      agronomically superior strains resulted in breaking the negative correlations
      between 1000 grain weight and high protein content and high DBC values. The
      methodology of DBC-Kjeldahl protein adopted in the present study is likely to be
      useful in identifying high lysine lines. The present study has shown considerable
      variability with respect to protein content and grain weight and has provided
      interesting genotypes which can be used in synthesising lines with improved
      nutritional quality and productivity in barley. The success in breaking the
      undesirable linkages to factors that impair the endosperm development is due to
      sufficient genetic variability in the initial breeding material as well as the
      use of suitable breeding procedures like the full-sib mating in the early
      segregating generations. 

PMID- 24301344
TI  - Chromosome pairing in tetraploid hybrids between Lolium perenne and L.
      multiflorum.
AB  - Chromosome association at first meiotic metaphase in tetraploid hybrids between
      Lolium perenne and L. multiflorum was compared with that in autotetraploid L.
      perenne. The hybrids were found to have significantly higher levels of bivalent
      frequency, and lower levels of multivalent and chiasma frequency. A significant
      increase in multivalent frequency with increasing chiasma formation was found in
      both groups, but the increase was much less in the hybrids. These differences in
      chromosome associations between the two groups must therefore reflect differences
      in chiasma distribution and it is suggested that the results indicate a
      significant degree of preferential bivalent pairing in the hybrids. 

PMID- 24301345
TI  - Induced mutants from dihaploid potatoes after pollen mother cell treatment.
AB  - Microspore mother cells of dihaploid Solanum tuberosum plants were mutagenically
      treated during the stage of meiosis. Mutagenesis was performed either by
      irradiation with x- or gamma-rays or by the application of nitrosomethylurethane
      or methylnitronitrosoguanidine. Then, by use of the anther culture technique, 913
      functional plants and 442 untreated control plants were regenerated. From the
      exposed plants seven distinct mutants could be isolated, predominantly
      chlorophyll deficient lines, while from the controls no clear-cut mutants arose.
      One mutant turned out to be photomorphogenetic in addition to having a
      chlorophyll defect. In addition to the production of mutants the treatments
      significantly increased the frequency of multicellular structure formation from
      microspores. 

PMID- 24301346
TI  - Genetic analysis of incompatibility in the diploid Ipomoea species closely
      related to the sweet potato.
AB  - In order to identify the genotypic constitutions of incompatibility in the
      diploid species, Ipomoea leucantha Jacq. (K221), which is most closely related to
      the sweet potato, the progenies derived from the reciprocal crosses, backcrosses
      and testcrosses were analysed. All the plants examined were self-incompatible,
      and pollen germination was inhibited on the stigma after incompatible
      pollinations. No reciprocal differences were found in the incompatibility
      reactions. In the progenies three incompatibility groups were observed which
      showed the rather simple segregation ratios. The homozygous plants for
      incompatibility alleles were obtained in the progenies. The experimental results
      demonstrated a sporophytic type of incompatibility controlled by a single locus
      with multiple S-alleles exhibiting a dominance relationship in both the pollen
      and the stigma. The plants obtained in the progenies had the following genotypes:
      S 1 S 2, S 1 S 3, S 2 S 2, S 2 S 3 and S 3 S 3. 

PMID- 24301347
TI  - Haploid embryogenesis in anther cultures of pigeon-pea (Cajanus cajan).
AB  - Pollen embryogenesis and callus showing a wide range of ploidy is induced in the
      in vitro cultured anthers of pigeon-pea. A suspension of pollen from such anthers
      incubated in drop cultures on agar medium develops further to form embryoids and
      colonies of callus. 

PMID- 24301348
TI  - Meiotic disjunction and embryonic lethality in sex-linked double-translocation
      heterozygous males of the onion fly, Hylemya antiqua (Meigen).
AB  - The frequencies of disjunction types in double-translocation heterozygous males
      (2(6)2(Y)6(2)6XY(2)) in Hylemya antiqua have been established in MII cells and
      eggs of testcrosses.Several disjunction types occurred but four predominated. A
      correlation was found between the frequencies of the disjunction types and the
      relative position of the centromeres. The frequency of numerical non-disjunction
      (NND) was 4%. Differences in frequency of NND between sex-linked and autosomal
      translocations of H. antiqua are discussed. A good correspondence between the
      frequencies of unbalanced karyotypes, and embryonic and larval mortality was
      found. The total genetic load which can be induced by the T14/T61 males is
      estimated to be 60-65%. Some duplication/deficiency karyotypes appeared to be
      viable in pupal and even adult stages. In 2(6)2(6)2(Y)6(2)6(2)X males a regular
      coorientation between 2(Y) and X was observed, in spite of non-homologous
      centromeres and a complicated synapsis of 2(Y). Application possibilities of the
      present material for genetic control of H. antiqua are discussed. 

PMID- 24301349
TI  - Genetic instability in mass-rearing colonies of a sex-linked translocation strain
      of Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) during a field trial of
      genetic control.
AB  - Genetic breakdown occurred in a strain of Lucilia cuprina constructed for the
      purpose of genetic control of this pest. The strain incorporated autosomal
      recessive eye colour mutations linked in repulsion with a translocation involving
      the Y chromosome (male-determining) and two autosomes. In the original strain
      females had white eyes and males were wild type. The spontaneous breakdown
      involved a failure of the sex-limited inheritance of the eye colour mutations.
      Characteristically the frequency of white-eyed males increased rapidly in the
      strain, whereas the frequencies of the three other phenotypically recognizable
      breakdown products did not. This suggested that the white-eyed males had a
      selective advantage over both the wild type males and the other breakdown
      products. Genetic analysis revealed that recombination, which is normally rare in
      L. cuprina males, is considerably more frequent in the presence of a Y-autosome
      translocation, but that recombination alone was insufficient to account for the
      rate of increase of the white-eyed males in the colony. Genetic and cytological
      analysis of the breakdown products revealed that reversion of the multi-break
      translocation also occurred, and that many of the white-eyed males had either
      only a Y-single-autosome translocation or no translocation at all; thus these
      males were more fertile than the wild type multi-translocation males. In
      addition, under colony cage conditions the white-eyed males may have had a
      behavioural advantage in competition with the wild type males. 

PMID- 24301350
TI  - Is Fisher's model necessary for the theory of population improvement?
AB  - It is shown here that genetic advance in one cycle of recurrent selection can be
      formulated directly in terms of covariances between relatives by application of
      the general statistical principle of linear prediction. For practical use of such
      formulae it is necessary to estimate the corresponding covariance between
      relatives from the mating design used. With General Combining Ability selection
      such estimation is direct. For other types of selection, it is necessary to
      derive associated covariances from other types of covariances but it is not
      necessary to use classical results of covariances between relatives in terms of
      genetic effects. Indeed, covariances can be derived without factorial
      decomposition of the genetic effects at one locus, i.e., without the concept of
      additivity and dominance. This approach allows a simple derivation of the genetic
      advance after n cycles of selection, followed by m generations of intercrossing,
      with a minimum of assumptions. 

PMID- 24301351
TI  - Limits of artificial selection under unbalanced mating systems.
AB  - The influence of unbalanced mating systems - factorial mating (FM) and random
      loss of families after a full diallel crossing (RS) - on the ultimate probability
      of gene fixation (u(Pi)) and the time required to fix or lose a gene (t(Pi)) are
      investigated. The average u(Pi) of these systems is smaller than that of random
      mating, and the range of u(Pi) for a given initial parental genotype combination
      is very large (close to one for most initial genotypic combinations). The average
      u(Pi) of different parental genotypic combinations of a given gene frequency are
      different. These systems accelerate the t(Pi). 

PMID- 24301352
TI  - An empirical model to estimate daily forest fire smoke exposure over a large
      geographic area using air quality, meteorological, and remote sensing data.
AB  - Exposure to forest fire smoke (FFS) is associated with a range of adverse health
      effects. The British Columbia Asthma Medication Surveillance (BCAMS) product was
      developed to detect potential impacts from FFS in British Columbia (BC), Canada.
      However, it has been a challenge to estimate FFS exposure with sufficient spatial
      coverage for the provincial population. We constructed an empirical model to
      estimate FFS-related fine particulate matter (PM2.5) for all populated areas of
      BC using data from the most extreme FFS days in 2003 through 2012. The input data
      included PM2.5 measurements on the previous day, remotely sensed aerosols,
      remotely sensed fires, hand-drawn tracings of smoke plumes from satellite images,
      fire danger ratings, and the atmospheric venting index. The final model explained
      71% of the variance in PM2.5 observations. Model performance was tested in days
      with high, moderate, and low levels of FFS, resulting in correlations from 0.57
      to 0.83. We also developed a method to assign the model estimates to geographical
      local health areas for use in BCAMS. The simplicity of the model allows easy
      application in time-constrained public health surveillance, and its sufficient
      spatial coverage suggests utility as an exposure assessment tool for
      epidemiologic studies on FFS exposure. 

PMID- 24301353
TI  - Using a biokinetic model to quantify and optimize cortisol measurements for acute
      and chronic environmental stress exposure during pregnancy.
AB  - To fully understand the potentially harmful effects of prenatal stress exposure
      impacts, it is necessary to quantify long-term and episodic stress exposure
      during pregnancy. There is a strong body of research relating psychological
      stress to elevated cortisol levels in biomarkers. Recently, maternal hair has
      been used to measure cortisol levels, and provides the unique opportunity to
      assess stress exposure throughout gestation. Understanding how cortisol in the
      hair is related to more common biomarkers, such as, blood, saliva and urine is
      currently lacking. Therefore, we developed a biokinetic model to quantify the
      relationships between hair, blood, saliva and urine cortisol concentrations using
      published literature values. Hair concentrations were used to retrospectively
      predict peaks in blood and saliva concentrations over days and months.
      Simulations showed realistic values in all compartments when results were
      compared with published literature. We also showed that the significant
      variability of cortisol in blood leads to a weak relationship between long-term
      and episodic measurements of stress. To our knowledge, this is the first
      integrative biokinetic cortisol model for blood, urine, hair and saliva. As such,
      it makes an important contribution to our understanding of cortisol as a
      biomarker and will be useful for future epidemiological studies. 

PMID- 24301355
TI  - Generalization in olfactory detection of chemical cues containing carbonyl
      functions by tiger salamanders (Ambystoma tigrinum).
AB  - Tiger salamanders generalize behaviorally between carbonyl-containing odorants
      (e.g., aldehydes or cycloalkanones). However, responding does not generalize from
      such odorants to stimulus compounds with comparable molecular shapes and
      dimensions but different functional groups. Discrimination between aldehydes and
      a ketone is temporarily impaired by two-step covalent modification of the
      olfactory epithelium. Two-step modification of the olfactory epithelia also
      impairs, but does not obliterate, olfactory detection, and generalization
      persists even during the period of impairment. These results are interpreted as
      implying the existence of carbonyl-binding, "generalist" olfactory receptors in
      addition to other classes of "generalist" receptors that are not affected by two
      step modification. Generalization is inferred to require overlap in the response
      profile of more than one class of receptor. 

PMID- 24301354
TI  - The Air Quality Health Index as a predictor of emergency department visits for
      ischemic stroke in Edmonton, Canada.
AB  - The Air Quality Health Index (AQHI) is an aggregate measure of outdoor air
      quality. We investigated associations between the AQHI and emergency department
      (ED) visits for acute ischemic stroke to validate the AQHI as a predictor of risk
      of morbidity from stroke. ED visits in Edmonton, Canada between 1998 and 2002
      were linked to hourly AQHI values and concentrations of carbon monoxide (CO),
      nitrogen dioxide (NO2), ozone, particulate matter with aerodynamic diameter less
      than 2.5 and 10 MUm, and sulfur dioxide. A time-stratified case-crossover
      analysis was employed, and measures of association were adjusted for temperature
      and relative humidity. The AQHI, NO2 and CO were positively associated with the
      number of ED visits for ischemic stroke during April-September, and associations
      were strongest for persons 75 years of age and older. In this age range, the odds
      ratios (95% confidence intervals) for an interquartile range increase of AQHI in
      1-24 h, 25-48 h, and 1-72 h lag periods were 1.23 (1.08-1.40), 1.15 (1.01-1.31),
      and 1.30 (1.10-1.54), respectively. Significant positive associations were also
      observed for NO2 and CO. Our finding that ED visits for stroke were significantly
      associated with the AQHI suggests that the AQHI may be a valid communication tool
      for air pollution morbidity effects related to stroke. 

PMID- 24301356
TI  - Phytotoxic properties of cnicin, a sesquiterpene lactone fromcentaurea maculosa
      (spotted knapweed).
AB  - Water and solvent extracts from the aerial tissues ofCentaurea maculosa, spotted
      knapweed, inhibited the root growth of lettuce. Column chromatography and lettuce
      bioassay of a chloroform extract led to the isolation of cnicin, a sesquiterpene
      lactone. Pure cnicin was bioassayed at 0, 1, 2, 4, 6, 8, and 10 mg/5 ml water
      with lettuce, created wheatgrass, bluebunch wheatgrass, rough fescue, western
      larch, lodgepole pine, and spotted knapweed. Germination was inhibited at one or
      more concentrations for all species except lodgepole pine and spotted knapweed.
      Growth, particularly of the roots, was retarded between 1 and 4 mg of cnicin.
      Lettuce, bluebunch wheatgrass, and spotted knapweed were inhibited significantly
      at all concentrations tested. 

PMID- 24301357
TI  - Defensive steroids from a carrion beetle (Silpha novaboracensis).
AB  - Two novel steroids, 3alpha,7beta-dihydroxy-14beta-pregn-4-en-15,20-dione (1) and
      3alpha,7beta, 20xi-trihydroxy-14beta-pregn-4-en-15-one (4), have been
      characterized from the rectal gland ofSilpha novaboracensis (Coleoptera:
      Silphidae). Judging from the function of comparable pregnanes in another species
      ofSilpha, the compounds may play an antipredator role. 

PMID- 24301358
TI  - Growth ofLeptinotarsa decemlineata larvae in response to simultaneous variation
      in protein and glycoalkaloid concentration.
AB  - Growth of larvae of the Colorado potato beetle,Leptinotarsa decemlineata (Say),
      as measured by weight gain, was determined when larvae were reared on synthetic
      diets containing measured quantities of protein and one of fiveSolanum
      glycoalkaloids. Data were analyzed to determine if growth was affected by these
      two aspects of phytochemical variation independently, or if there was a
      significant interaction component in larval weight gain to simultaneous variation
      in protein and glycoalkaloid concentration. For four of the five glycoalkaloids
      examined, a bivariate regression model without interaction accurately accounted
      for growth ofL. decemlineata larvae. For alpha-tomatine, however, a regression
      model with the addition of a (protein * glycoalkaloid) interaction term more
      accurately accounted for larval growth. The influence of this interaction was
      less than either protein or glycoalkaloid concentration alone. The variation in
      protein concentration accounted for most of the variation in larval growth, and
      high protein concentrations could more than offset the effect of high
      concentration of any of the five glycoalkaloids. 

PMID- 24301359
TI  - Cardenolide content and thin-layer chromatography profiles of monarch
      butterflies,danaus plexippus L., and their larval host-plant milkweed,asclepias
      viridis walt., in northwestern louisiana.
AB  - This paper is the first in a series on cardenolide fingerprinting of monarch
      butterflies and their host-plant milkweeds in the eastern United States.
      Spectrophotometric determinations of the gross cardenolide content of 60Asclepias
      viridis plants in northwestern Louisiana indicate a positively skewed variation
      ranging from 95 to 432 upsilong/0.1 g dry weight with a mean of 245 upsilong/0.1
      g. Butterflies reared individually on these plants contained a normal cardenolide
      distribution ranging from 73 to 591 upsilong/0.1 g dry weight with a mean of 337
      upsilong/0.1 g. The uptake of cardenolide by the butterflies best fit a
      logarithmic function of the plant concentration. Female monarchs (385
      upsilong/0.l g) contained significantly greater mean cardenolide concentrations
      than did males (287 upsilong/0.1 g). No indications of a metabolic cost for
      either cardenolide ingestion or storage were adduced from size or dry weight
      data. Thin-layer chromatograms of 24 individual plant-butterfly pairs developed
      in two solvent systems resolved 21 individual spots in the plants and 15 in the
      butterflies.A. viridis plants appear to contain several relatively nonpolar
      cardenolides of the calotropagenin series which are metabolized to the more polar
      3'-hydroxy derivatives calactin and calotropin as well as to calotropagenin in
      the butterflies. The epoxy cardenolides labriformin and labriformidin were
      absent, although desglucosyrioside (a 3'-hydroxy derivative) appeared present in
      both plants and butterflies. Quantitative evaluation of theR f values, spot
      intensities, and probabilities of occurrence in the chloroform-methanol-formamide
      TLC system produced a cardenolide fingerprint clearly distinct from those
      previously established for monarchs reared on otherAsclepias species, supporting
      the use of fingerprints to make ecological predictions concerning larval host
      plant utilization.A. viridis is the predominant early spring milkweed throughout
      most of the south central United States and may be important in providing
      chemical protection to spring and early summer generation monarchs in the eastern
      United States. 

PMID- 24301360
TI  - Musk deer (Moschus moschiferus): Reinvestigation of main lipid components from
      preputial gland secretion.
AB  - The qualitative and quantitative composition of the principal lipid constituents
      of Siberian musk deer (Moschus moschiferus) preputial gland secretion, main odor
      carriers and potential precursors of odorous substances, was investigated by
      means of high-performance liquid chromatography. Free fatty acids and phenols
      (10%), waxes (38%), and steroids (38%) were found to be the main groups of the
      secretion lipids. Cholestanol (I), cholesterol (II), androsterone (III), Delta(4)
      3alpha-hydroxy-17-ketoandrostene (IV), 5beta, 3alpha-hydroxy-17-ketoandrostane
      (V), 5alpha, 3beta, 17alpha-dihydroxyandrostane (VI), 5beta, 3alpha, 17beta
      dihydroxyandrostane (VII), and 5beta, 3alpha, 17alpha-dihydroxyandrostane (VIII)
      were isolated from the steroid fraction and their structures confirmed by IR,
      PMR, and mass spectra. 3-Methylpentadecanone (muscone) was not identified among
      the secretion lipids. Preputial gland secretion stimulated sex behavior of musk
      deer females. 

PMID- 24301361
TI  - Interruption of response ofDendroctonus brevicomis to attractive pheromone by
      release of pheromone at several rates and spacings.
AB  - The number of western pine beetles,Dendroctonus brevicomis, trapped at the center
      of three 90 * 90-m plots was reduced during a 16-hr period after surrounding an
      attractive source ofexo-brevicomin, frontalin, and myrcene with 16, 48, or 168
      sources of the same attractant. Compounds were released from the center of the
      plot at 1 mg/16 hr/compound, and from the surrounding sources at 4-280 mg/16
      hr/compound. About half of these amounts was released between 1530 hr and 1930
      hr, the period of peak beetle flight. No treatment differences were apparent in
      reduction of catch within the range of release rates and spacings tested. When
      compounds were released continuously from 168 stations for 17 days, catch at the
      center of a plot was generally lower than catch before or after this period, but
      fluctuated daily. More beetles were caught on traps hung on ponderosa pines
      within a plot and the number of these traps catching beetles was greater when
      compounds were released from all stations than from only the center station.
      Beetles caught on traps were attracted into the plots from the surrounding
      forest, but appeared to be dispersed within the plot when compounds were released
      from many stations.D. brevicomis attacked at least 91 trees in the plots, of
      which 25 were killed during two summers. 

PMID- 24301362
TI  - Extractives of seeds of the meliaceae: Effects onSpodoptera frugiperda (J.E.
      Smith),Acalymma vittatum (F.), andArtemia salina Leach.
AB  - Hexane and ethanol extracts of seeds from 22 species of plants of the family
      Meliaceae from a number of countries were prepared. The extracts were submitted
      to antifeedant and toxicity bioassays utilizing fall armyworm [Spodoptera
      frugiperda (J.E. Smith)] (Lepidoptera: Noctuidae) larvae and striped cucumber
      beetle [Acalymma vittatum (F.)] (Coleoptera: Chrysomelidae) adults. Toxicity
      tests were also performed with brine shrimp,Anemia salina Leach. Feeding
      inhibition and mortality produced by some of these extracts were comparable to
      and, in certain cases, slightly greater than the effects produced by comparable
      neem (Azadiracta indica A. Juss.) seed preparations. Brine shrimp toxicity data
      do not extrapolate to insect activity, and vice versa. 

PMID- 24301363
TI  - Kairomone-mediated host finding by spruce budworm egg parasite,Trichogramma
      minutum.
AB  - The host-finding responses of the egg parasite,Trichogramma minutum Riley, reared
      from its natural host,Choristoneura fumiferana (Clemens) and a laboratory
      host,Sitotroga cerealella (Oliver), to hexane extracts of scales of these hosts
      were compared in laboratory experiments. When presented withC. fumiferana eggs on
      filter papers treated with hexane and hexane extract of grain moth scales, egg
      finding byT. minutum was random. When presented with budworm eggs on filter
      papers treated with hexane and hexane extract of budworm scales,T. minutum found
      significantly more eggs on extract-treated filter papers, indicating the presence
      of kairomones on the scales of spruce budworms.T. minutum responded to kairomone
      treated patches with a localized search behavior characterized by intense
      antennal tapping, decreased locomotion and increased turning within the patch,
      and repeated returns to the patch. In the absence of successful host finding,
      this response slowly waned. No significant difference in behavior ofT. minutum
      reared on eitherC. fumiferana orS. cerealella was observed. 

PMID- 24301364
TI  - Aldrin epoxidase activity and cytochrome P-450 content of sawfly
      larvae,Pergagrapta polita Leach (Hymenoptera: Pergidae) feeding on twoEucalyptus
      species.
AB  - Aldrin epoxidase and cytochrome P-450 levels were determined in sawfly
      larvae,Pergagrapta polita Leach. Of the tissues examined the anterior portion of
      the midgut had the highest levels of aldrin epoxidase activity and cytochrome P
      450 content, 3.56 nmol dieldrin produced/min/mg protein and 1.28 nmol/mg protein,
      respectively. No significant differences in aldrin epoxidase activities were
      observed between groups of larvae representing the last three larval instars and
      between larvae feeding on two eucalypt species. 

PMID- 24301365
TI  - Linamarin and histamine in the defense of adultZygaena filipendulae.
AB  - We determined the protective values of histamine and linamarin to an aposematic
      moth,Zygaena filipendulae. Using ion-exchange resin techniques, we found that the
      mean histamine concentrations in the wings were 0.061 +/- 0.047 MUg/mg and 0.013
      +/- 0.0051 in the moths' bodies (totals: 0.586 MUg and 2.921 MUg, respectively,
      all wet weights). Average HCN evolution (mainly from the bitter cyanogen
      linamarin) from the wings was 0.049 +/- 0.41 MUg/mg (0.426 MUg/ml of linamarin
      could produce this amount of HCN) and 0.029 +/- 0.0026 MUg/mg HCN (0.281 MUg/mg
      linamarin) evolved from the bodies (total linamarin 4.09 MUg and 61.258 MUg,
      respectively, all wet weights). Therefore, higher concentrations of toxicants
      were found in the part of the body most liable to initial attack. We found, in
      offering various toxic solutions to 10 common quails, that 0.1% linamarin (mean
      linamarin consumed equal to about 70% of the average total wing content) but 1.0%
      histamine (mean histamine consumed equal to that found in about 8.9 average wing
      sets) solutions significantly lowered drinking rates. However, combination
      solutions were still effectively aversive at 0.001% histamine plus 0.028%
      linamarin. This synergism would allow a moth under local abiotic or dietary
      stress to elaborate substantially less of one or both compounds than that
      normally synthesized. The implications to kin selection are discussed. 

PMID- 24301366
TI  - Sex pheromone blend discrimination by male moths fromE andZ strains of European
      corn borer.
AB  - Sex pheromone behavioral responses were analyzed in a flight tunnel with European
      corn borer,Ostrinia nubilalis (Hubner), males from three distinct populations.
      Males from a bivoltine and a univoltine biotype using a 97.8?2.2 blend (Z
      strains) of (Z)- and (E)-11-tetradecenyl acetate were assayed with treatments
      containing 0, 0.5, 1, and 3% of theE isomer. Males from neither population
      oriented in the plume to the 100%Z treatment, but bivoltine males oriented and
      flew to the source to the other three treatments, whereas univoltine males
      oriented and flew to the source only to the 1 % and 3 %E treatments. Males from a
      bivoltine biotype using a 1?99 blend ofZ/E isomers (E strain) were assayed with
      sources containing 0, 0.5, 1, and 3% of theZ isomer. Males did not orient to the
      0%Z source, but oriented and flew to the source to the other three treatments. In
      addition to using opposite geometric isomers for the main pheromone component,
      the bivoltineE strain differed from the bivoltineZ strain by producing and
      responding better to 1 % of the minor component and by storing 3 times more
      pheromone in the female glands. Contrary to previous reports, the blend of two
      pheromone components is significantly better than the main component alone in
      eliciting oriented flight and close-range behavior with males from all three
      populations of European corn borer. 

PMID- 24301367
TI  - Odor similarity between stress-inducing odorants in wistar rats.
AB  - Odor similarity to the odor of 4-mercapto-4-methyl-2-pentanone (I) was measured
      on eight rats by generalization of a conditioned avoidance response tocis-
      andtrans-8-mercapto-p-menthan-3-one (II and III), 3-mercapto-3-methyl-2-pentanone
      (V), andt-amyl mercaptan (VI). Previously, these odorants had been found to
      induce stress in rats in an open-field situation. In the present experiment, rats
      generalized the avoidance response learned with I, for V, VI, and to a lesser
      extenttrans-isomer III, implying odor similarities;cis isomer II was
      discriminated. Odor similarity between mercapto ketone I and mercaptan VI is
      surprising since VI lacks the keto group. 

PMID- 24301368
TI  - Residual activity of oviposition-deterring pheromone inRhagoletis pomonella
      (Diptera: Tephritidae) and female response to infested fruit.
AB  - Under dry conditions, oviposition-deterring pheromone (ODP) of the apple maggot
      fly (Rhagoletis pomonella Walsh) on host fruit proved deterrent to ovipositing
      females for at least three weeks, with a half-life of ca. 11 days. There was no
      difference in decline of residual activity under lab vs. field conditions or
      between fly-deposited ODP vs. an application of a water extract of ODP. A decline
      in pheromone activity resulted from exposure to both natural and simulated
      rainfall. For natural rainfall, greatest losses (50- 61%) in activity resulted
      from high-intensity rains, with substantially less activity lost (13-35%)
      following light or moderate intensity rains.R. pomonella females discriminated
      against fruit without ODP but with conspecific larvae. Discrimination against
      infested fruit was manifested within fewer days following infestation of small
      fruit (9 mm diam.) as compared to larger fruit (15 mm diam.). 

PMID- 24301369
TI  - Stereospecific synthesis of (Z,Z)-3,5-tetradecadienoic acid, a component
      ofAttagenus elongatulus (Casey) pheromone.
AB  - A simple stereospecific synthesis of (Z,Z)-3,5-tetradecadienoic acid is described
      based upon coupling of 1-decyne and 3-butyn-1-ol to give 3,5-tetradecadiyn-1-ol.
      Subsequent reduction of the diyne to (Z,Z)-3,5-tetradecadien-1-ol and oxidation
      of the dienol gave the desired acid.Attagenus elongatulus were strongly attracted
      to the pure acid. 

PMID- 24301370
TI  - Allelochemicals from palmer amaranth,Amaranthus palmeri S. Wats.
AB  - The presence of Palmer amaranth (AMAPA) residues in the soil reduced fresh weight
      accumulation in onions and carrots and markedly decreased seedling field
      establishment of carrots. Solid-phase separation techniques were used to isolate
      fractions containing water-soluble organic compounds from AMAPA residues and soil
      amended with such residues. At concentrations of 20-100 mg/liter most of the
      organic solids thus extracted were inactive in seed germination assays using
      onion, carrot, AMAPA, and tomato seeds. Extracts from the roots of AMAPA
      increased 72-hr germination percentages in carrot, AMAPA, and tomato. A time
      study of AMAPA residue decomposition in soil showed an increase in extractable
      inhibitors of onion germination after 62 days but no other significant changes in
      the activity. The most active allelochemicals from AMAPA proved to be volatile
      compounds. Volatiles emitted by soil containing AMAPA residues and by the dried
      and partially rehydrated leaf and flower residues themselves reduced carrot and
      tomato seed germination to less than 7%. Freshly harvested aerial AMAPA inhibited
      only carrot seed. Germination of AMAPA and carrot seeds was retarded by exposure
      to volatiles from dried AMAPA residues. Residues from AMAPA grown in Texas and
      Louisiana exhibited comparable inhibitory activity after air-drying two weeks.
      Onion seeds were also inhibited by volatiles from AMAPA residues. 

PMID- 24301371
TI  - Ozone-induced changes in host-plant suitability: Interactions ofKeiferia
      lycopersicella andLycopersicon esculentum.
AB  - Tomato pinworms,Keiferia lycopersicella (Walsingham), survived better and
      developed faster on tomato plants,Lycopersicon esculentum Mill., damaged by ozone
      than on plants not subjected to ozone fumigation. Other measures of fitness,
      including survival during pupation, sex ratio of adults, female longevity, and
      fecundity, were not affected. Analyses of ozonated foliage at zero, two, and
      seven days following fumigation demonstrated a transient but significant increase
      (18-24%) in soluble protein concentration. Although the concentration of the
      total free amino acids in ozonated foliage did not increase significantly,
      significant changes were observed in at least 10 specific amino acids, some of
      which are critical for either insect development or the production of plant
      defensive chemicals. A reduction in total nitrogen in ozonated foliage at seven
      days postfumigation indicated that nitrogen was being translocated to other
      portions of the plant. The implications of increases in assimilable forms of
      nitrogen in ozonated foliage, which lead to improved host-plant suitability for
      insect herbivores, are discussed both in relation to some current ecological
      theories and in regard to pest-management strategies. 

PMID- 24301372
TI  - Oviposition deterrent from eggs ofCallosobruchus maculatus: Spacing mechanism or
      artifact?
AB  - Females ofCallosobruchus maculatus (F.) avoid ovipositing on host seeds already
      bearing conspecific eggs, and thus distribute eggs evenly among seeds. This
      behavior was presumed to be mediated by an ether-soluble "oviposition marker"
      that is deposited with the egg and can be extracted from egg-laden artificial
      hosts (glass beads). Ablation experiments revealed that the true factors
      promoting an even dispersion of eggs were perceived by the maxillary and labial
      palpi. In contrast, receptors on the antennae were largely responsible for
      avoidance of seeds treated with "oviposition marker." Taken together, these
      results suggest that a careful distinction should be drawn between factors that
      promote spacing of eggs under natural conditions and general oviposition
      deterrents that may be isolated from both sexes. 

PMID- 24301373
TI  - Morphological and mechanical changes in juvenile red-eared slider turtle
      (Trachemys scripta elegans) shells during ontogeny.
AB  - Turtles experience numerous modifications in the morphological, physiological,
      and mechanical characteristics of their shells through ontogeny. Although a
      general picture is available of the nature of these modifications, few
      quantitative studies have been conducted on changes in turtle shell shape through
      ontogeny, and none on changes in strength or rigidity. This study investigates
      the morphological and mechanical changes that juvenile Trachemys scripta elegans
      undergo as they increase in size. Morphology and shell rigidity were quantified
      in a sample of 36 alcohol-preserved juvenile Trachemys scripta elegans.
      Morphometric information was used to create finite element models of all
      specimens. These models were used to assess the mechanical behavior of the shells
      under various loading conditions. Overall, we find that turtles experience
      complementary changes in size, shape, deformability, and relative strength as
      they grow. As turtles age their shells become larger, more elongate, relatively
      flatter, and more rigid. These changes are associated with decreases in relative
      (size independent) strength, even though the shells of larger turtles are
      stronger in an absolute sense. Decreased deformability is primarily due to
      changes in the size of the animals. Residual variation in deformability cannot be
      explained by changes in shell shape. This variation is more likely due to changes
      in the degree of connectedness of the skeletal elements in the turtle's shells,
      along with changes in the thickness and degree of mineralization of shell bone.
      We suggest that the mechanical implications of shell size, shape, and
      deformability may have a large impact on survivorship and development in members
      of this species as they mature.

PMID- 24301374
TI  - Decrease of polypeptides in the PS I antenna complex with increasing growth
      irradiance in the red alga Porphyridium cruentum.
AB  - Thylakoids isolated from cells of the red alga Porphyridium cruentum exhibit an
      increased PS I activity on a chlorophyll basis with increasing growth irradiance,
      even though the stoichiometry of Photosystems I and II in such cells shows little
      change (Cunningham et al. (1989) Plant Physiol 91: 1179-1187). PS I activity was
      26% greater in thylakoids of cells acclimated at 280 MUmol photons . m(-2) . s(
      1) (VHL) than in cells acclimated at 10 MUmol photons . m(-2) . s(-1) (LL),
      indicating a change in the light absorbance capacity of PS I. Upon isolating PS I
      holocomplexes from VHL cells it was found that they contained 132+/-9 Chl/P700
      while those obtained from LL cells had 165+/-4 Chl/P700. Examination of the
      polypeptide composition of PS I holocomplexes on SDS-PAGE showed a notable
      decrease of three polypeptides (19.5, 21.0 and 22 kDa) in VHL-complexes relative
      to LL-complexes. These polypeptides belong to a novel LHC I complex, recently
      discovered in red algae (Wolfe et al. (1994a) Nature 367: 566-568), that lacks
      Chl b and includes at least six different polypeptides. We suggest that the
      decrease in PS I Chl antenna size observed with increasing irradiance is
      attributable to changes occurring in the LHC I-antenna complex. Evidence for a
      Chl-binding antenna complex associated with PS II core complexes is lacking at
      this point. LHC II-type polypeptides were not observed in functionally active PS
      II preparations (Wolfe et al. (1994b) Biochimica Biophysica Acta 1188: 357-366),
      nor did we detect polypeptides that showed immunocross-reactivity with LHC II
      specific antisera (made to Chlamydomonas and Euglena LHC II). 

PMID- 24301375
TI  - Coregulation of electron transport through PS I by Cyt b 6 f, excitation capture
      by P700 and acceptor side reduction. Time kinetics and electron transport
      requirement.
AB  - Regulation of electron transport rate through Photosystem I (PS I) was
      investigated in intact sunflower leaves. The rate constant of electron donation
      via the cytochrome b 6 f complex (kq, s(-1)) was obtained from the
      postillumination P700(+) reduction rate, measured as the exponential decay of the
      light-dark difference (D830) of the 830 nm transmission signal. D830
      corresponding to maximum oxidisable P700 (D830m) was obtained by applying white
      light flashes of different intensity and extrapolating the plot of the quantum
      yield Y vs. D830 to the axis of abscissae (Y->0). Maximum quantum yield of PS I
      at completely reduced P700 (Ym) was obtained by extrapolating the same plot to
      the axis of ordinates (D830->0). Regulation of kq, D830m and Ym under rate
      limiting CO2 and O2 concentrations applied after air (21% O2, 310 ppm CO2) was
      investigated. The amplitude of the downregulation of kq (photosynthetic control)
      was maximal when electron transport rate (ETR) was limited to about 3 nmol cm(-2)
      s(-1) and decreased when ETR was higher or lower. Downregulation did not occur in
      the absence of CO2 and O2. These gases acted only as substrates of
      ribulosebisphosphate carboxylase-oxygenase, no high-affinity reaction of O2
      leading to enhanced photosynthetic control (e.g. Mehler reaction) was detected.
      After the transition, D830m at first decreased and then increased again, showing
      that the reduction of the PS I acceptor side disappeared as a result of the
      downregulation of kq. The variation of Ym had two reasons, PS I acceptor side
      reduction and variable excitation capture efficiency by P700. It is concluded
      that electron transport through PS I is coregulated by the rate of plastoquinol
      oxidation at Cyt b 6 f, excitation capture efficiency by P700, and by acceptor
      side reduction. 

PMID- 24301376
TI  - Rearrangement of light harvesting bacteriochlorophyll homologues as a response of
      green sulfur bacteria to low light intensities.
AB  - The pigment composition of two species of green-colored BChl c-containing green
      sulfur bacteria (Chlorobium limicola and C. chlorovibrioides) and two species of
      brown-colored BChl e-containing ones (C. phaeobacteroides and C. phaeovibrioides)
      incubated at different light intensities have been studied. All species responded
      to the reduction of light intensity from 50 to 1 MUEinstein(E) m(-2) s(-1) by an
      increase in the specific content of light harvesting pigments,
      bacteriochlorophylls and carotenoids. At critical light intensities (0.5 to 0.1
      MUE m(-2) s(-1)) only brown-colored chlorobia were able to grow, though at low
      specific rates (0.002 days(-1) mg prot(-1)). High variations in the relative
      content of farnesyl-bacteriochlorophyll homologues were found, in particular BChl
      e 1 and BChl e 4, which were tentatively identified as [M, E] and [I, E] BChlF e,
      respectively. The former was almost completely lost upon reduction of light
      intensity from 50 to 0.1 MUE m(-2) s(-1), whereas the latter increased from 7.2
      to 38.4% and from 13.6 to 42.0% in C. phaeobacteroides and C. phaeovibrioides,
      respectively. This increase in the content of highly alkylated pigment molecules
      inside the chlorosomes of brown species is interpreted as a physiological
      mechanism to improve the efficiency of energy transfer towards the reaction
      center. This study provides some clues for understanding the physiological basis
      of the adaptation of brown species to extremely low light intensities. 

PMID- 24301377
TI  - Interaction of the photosynthetic and respiratory electron transport chains
      producing slow O2 signals under flashing light in Synechocystis sp. PCC 6803.
AB  - We investigated the slow signal of apparent O2 release under brief light flashes
      by using mutants of Synechocystis sp. PCC 6803 which lacked CP43 and D1. The slow
      signal was present at higher amplitudes in the mutants. It was inhibited by
      starving the mutants of glucose (>90%), by 10 mM NaN3 (85%) and by boiling
      samples for 2 min (100%). In the mutants and in the wild-type, the slow signal
      was 95% inhibited by the combination of DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone) and HQNO (2-n-heptyl-4-hydroxyquinoline-N-oxide). In the wild type,
      the addition of DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea) or CCCP
      (carbonylcyanide m-chlorophenylhydrazone) completely inhibited photosynthetic O2
      evolution, yet failed to inhibit the slow signal. We explain the kinetics of the
      wild-type signal as a positive deflection due to the inhibition of respiration by
      PS I activity, and a negative deflection due to the stimulation of respiration by
      electrons originating from PS II. We found no evidence of a 'meta-stable S3' in
      Synechocystis sp. PCC 6803 that could contribute to the slow signal of apparent
      O2 release. We present a calculation which involves only averaging, division and
      subtraction, that can remove the contribution of the slow signal from the true
      photosynthetic O2 signal and provide up to a 10-fold improved accuracy of the S
      state models. 

PMID- 24301378
TI  - Rapid isolation of photosystem I chlorophyll-binding proteins by anion exchange
      perfusion chromatography.
AB  - With the new method of anion exchange perfusion chromatography we have devised an
      extremely rapid technique to subfractionate spinach Photosystem I into its
      chlorophyll a containing core complex and various components of the Photosystem I
      light-harvesting antenna (LHC I). The isolation time for the LHC I subcomplexes
      following solubilisation of native Photosystem I was reduced from 50 h using
      traditional density centrifugation procedures down to only 10-25 min by perfusion
      chromatography. Within this very short period of isolation, LHC I has been
      obtained as subfractions highly enriched in Lhca2+3 (LHC I-680) and Lhca1+4 (LHC
      I-730). Moreover, other highly enriched subfractions of LHC I such as Lhca2,
      Lhca3 and Lhca1+2+4 were obtained where the later two populations have not
      previously been obtained in a soluble form and without the use of SDS. These
      various subfractions of the LHC I antenna have been characterised by absorption
      spectroscopy, 77 K fluorescence-spectroscopy and SDS-PAGE demonstrating their
      identities, functional intactness and purity. Furthermore, the analyses located a
      chlorophyll b pool to preferentially transfer its excitation energy to the low
      energy F735 chromophore, and located specifically the origin of the 730 nm
      fluorescence to the Lhca4 component. It was also revealed that Lhca2 and Lhca3
      have identical light-harvesting properties. The isolated Photosystem I core
      complex showed high electron transport capacity (1535 MUmoles O2 mg Chl(-1) h(
      1)) and low fluorescence yield (0.4%) demonstrating its high functional
      integrity. The very rapid isolation procedure based upon perfusion chromatography
      should in a significant way facilitate the subfractionation of Photosystem I
      proteins and thereby allow more accurate functional and structural studies of
      individual components. 

PMID- 24301379
TI  - Functional analysis of the iron-stress induced CP 43' polypeptide of PS II in the
      cyanobacterium Synechococcus sp. PCC 7942.
AB  - Under conditions of iron-stress, the Photosystem II associated chlorophyll a
      protein complex designated CP 43', which is encoded by the isiA gene, becomes the
      major pigment-protein complex in Synechococcus sp. PCC 7942. The isiB gene, which
      is located immediately downstream of isiA, encodes the protein flavodoxin, which
      can functionally replace ferredoxin under conditions of iron stress. We have
      constructed two cyanobacterial insertion mutants which are lacking (i) the CP 43'
      apoprotein (designated isiA (-)) and (ii) flavodoxin (designated isiB (-)). The
      function of CP 43' was studied by comparing the cell characteristics, PS II
      functional absorption cross-sections and Chl a fluorescence parameters from the
      wild-type, isiA (-) and isiB (-) strains grown under iron-stressed conditions. In
      all strains grown under iron deprivation, the cell number doubling time was
      maintained despite marked changes in pigment composition and other cell
      characteristics. This indicates that iron-starved cells remained viable and that
      their altered phenotype suggests an adequate acclimation to low iron even in
      absence of CP 43' and/or flavodoxin. Under both iron conditions, no differences
      were detected between the three strains in the functional absorption crossection
      of PS II determined from single turnover flash saturation curves of Chl a
      fluorescence. This demonstrates that CP 43' is not part of the functional light
      harvesting antenna for PS II. In the wild-type and the isiB (-) strain grown
      under iron-deficient conditions, CP 43' was present in the thylakoid membrane as
      an uncoupled Chl-protein complex. This was indicated by (1) an increase of the
      yield of prompt Chl a fluorescence (Fo) and (2) the persistence after PS II trap
      closure of a fast fluorescence decay component showing a maximum at 685 nm. 

PMID- 24301380
TI  - Functional phycobilisome core structures in a phycocyanin-less mutant of
      cyanobacterium Synechococcus sp. PCC 7942.
AB  - We have constructed a mutant Synechococcus sp. PCC 7942, termed R2HECAT, in which
      the entire phycobilisome rod operon has been deleted. In the whole cell
      absorption spectra of R2HECAT, the peak corresponding to phycocyanin (PC),
      lambdamax~620 nm, could not be detected. However, a single pigment-protein
      fraction with lambdamax=654 nm could be isolated on sucrose gradients from
      R2HECAT. Analysis of this pigment-protein fraction by non-denaturing PAGE
      indicates an apparent molecular mass of about 1200-1300 kDa. On exposure to low
      temperature, the isolated pigment-protein complex dissociated to a protein
      complex with a molecular mass of about 560 kDa. When analysed by SDS-PAGE, the
      pigment-protein fraction was found to consist of the core polypeptides but lacked
      PC, 27, 33, 30, and the 9 kDa polypeptides which are a part of the rods. All the
      chromophore bearing polypeptides of the core were found to be chromophorylated.
      CD as well as absorption spectra showed the expected maxima around 652 and 675 nm
      from allophycocyanin (APC) and allophycocyanin B (APC-B) chromophores. Low
      temperature fluorescence and excitation spectra also showed that the core
      particles were fully functional with respect to the energy transfer between the
      APC chromophores. We conclude that PC and therefore the rods are dispensable for
      the survival of Synechococcus sp. PCC 7942. The results indicate that stable and
      functional core can assemble in absence of the rods. These rod-less phycobilisome
      core is able to transfer energy to Photosystem II. 

PMID- 24301381
TI  - Restoration of the high potential form of cytochrome b-559 through the
      photoreactivation of Tris-inactivated oxygen-evolving center.
AB  - Restoration of a high potential (HP) form of cytochrome b-559 (Cyt b-559) from a
      low potential (LP) form was the primary process in the reconstitution of O2
      evolving center during the photoreactivation of Tris-inactivated chloroplasts. In
      normal chloroplasts, about 0.5 to 0.7 mol of Cyt b-559 was present in the HP form
      per 400 chlorophyll molecules. However, the HP form was converted to the LP form
      when the O2-evolving center was inactivated by 0.8 M alkaline Tris-washing (pH
      9.1). The inactivation was reversible and both the Cyt b-559 HP form and the O2
      evolving activity were restored by incubating the inactivated chloroplasts with
      weak light, Mn(2+), Ca(2+) and an electron donor (photoreactivation). The
      recovery of the HP form preceded the recovery of O2-evolving activity. 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone (DBMIB) did not inhibit the recovery of the HP form. Thus, the
      recovery of Cyt b-559 HP form was the primary reaction in the photoreactivation,
      which was stimulated by the light-induced redox reaction of the PS-II core
      center. 

PMID- 24301382
TI  - Tetanus is still a deadly disease: a report of six tetanus cases and reminder of
      our knowledge.
AB  - We analysed the data in the medical records of six patients admitted for tetanus
      in the intensive care unit (ICU) of the anaesthesia department in the Medical
      Faculty of Ataturk University from 1 January 2010 to 31 December 2012. All
      patients received the generalized form of treatment for tetanus in the ICU. The
      average age of the patients was 65.33 +/- 13.45 years. Treatment modalities were
      administered to the patients in accordance with the literature. Four patients
      died despite all therapeutic interventions and two patients were discharged
      uneventfully. All those who died had chronic disease and infected wounds on their
      head, but only one patient had an infected wound on his leg. The surviving
      patients had no chronic illnesses but did have injuries on their legs. The
      presence of chronic disease increases tetanus-related mortality. More information
      about the disease must be made available in order to make it preventable with
      regular vaccinations.

PMID- 24301383
TI  - Ruthenium catalyzed selective hydrosilylation of aldehydes.
AB  - A chemoselective hydrosilylation method for aldehydes is developed using a
      ruthenium catalyst [(Ru(p-cymene)Cl2)2] and triethylsilane; a mono hydride
      bridged dinuclear complex [{(eta(6)-p-cymene)RuCl}2(MU-H-MU-Cl)] and a Ru(iv)
      mononuclear dihydride complex [(eta(6)-p-cymene)Ru(H)2(SiEt3)2] are identified as
      potential intermediates in the reaction and the proposed catalytic cycle involves
      a 1,3-hydride migration. 

PMID- 24301384
TI  - The rise of food poverty in the UK.

PMID- 24301385
TI  - The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death
      in neural progenitors.
AB  - The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its
      relevance in the mammalian mitotic cell cycle is still unclear. Here we show that
      genetic ablation of Cdh1 in the developing nervous system results in hypoplastic
      brain and hydrocephalus. These defects correlate with enhanced levels of Cdh1
      substrates and increased entry into the S phase in neural progenitors. However,
      cell division is prevented in the absence of Cdh1 due to hyperactivation of
      cyclin-dependent kinases, replicative stress, induction of p53, G2 arrest and
      apoptotic death of these progenitor cells. Concomitant ablation of p53 rescues
      apoptosis but not replicative stress, resulting in the presence of damaged
      neurons throughout the adult brain. These data indicate that the inactivation of
      Cdh1 in vivo results in replicative stress, cell cycle arrest and cell death,
      supporting recent therapeutic proposals aimed to inhibit the APC/C in tumours. 

PMID- 24301386
TI  - Mission versus reality in emergency care.

PMID- 24301387
TI  - The ambulance industry struggles to go the distance.

PMID- 24301388
TI  - Emergency care: then, now, and next.
AB  - Five decades ago, hospitals staffed their emergency rooms with rotating community
      physicians or unsupervised hospital staff. Ambulance service was frequently
      provided by a local funeral home. Beginning in the late 1960s and accelerating
      thereafter, emergency care swiftly evolved into its current form. Today, modern
      emergency departments not only are capable of providing around-the-clock
      lifesaving care in individual emergencies and disasters. They also conduct timely
      diagnostic workups, provide access to after-hours acute care, and serve as the
      "safety net of the safety net" for millions of low-income and uninsured patients.
      But the field's success has led to a new set of challenges. To overcome them,
      emergency care must become more integrated, regionalized, prevention oriented,
      and innovative. 

PMID- 24301389
TI  - The enduring role of the Emergency Medical Treatment and Active Labor Act.
AB  - The Emergency Medical Treatment and Active Labor Act (EMTALA) is a seminal law
      that imposes screening, stabilization, and transfer duties on all Medicare
      participating hospitals that have emergency departments. More than twenty-five
      years after its enactment, EMTALA continues to generate controversy over the
      scope and depth of its obligations on issues ranging from the nature of the
      screening obligation and rules regarding on-call specialists to whether EMTALA's
      stabilization protections exclude emergency inpatients. Despite ongoing questions
      that flow from its detailed provisions, EMTALA is an enduring testament to
      society's evolving views that hospitals must provide emergency care not only to
      their established patients but to the broader communities they serve. 

PMID- 24301390
TI  - Creating integrated networks of emergency care: from vision to value.
AB  - Emergency care is an essential component of the care delivery system in the
      United States, but it received little attention during the debates about health
      care reform. As a result, US emergency care remains outdated and fragmented. We
      provide an overview of efforts to regionalize emergency care in the United
      States, and we both identify challenges to change and recommend next steps in
      five domains: people, quality and processes, technology, finances, and
      jurisdictional politics. We offer a commonsense approach to increasing the value
      of emergency care delivery by developing regionalized integrated networks of
      emergency care that take advantage of emerging changes in the health system and
      are designed to meet time-sensitive patient needs. 

PMID- 24301391
TI  - Sustaining a coordinated, regional approach to trauma and emergency care is
      critical to patient health care needs.
AB  - Trauma systems provide an organized approach to the care of injured patients
      within a defined geographic region. When fully operational, the systems ensure a
      continuum of care involving public access through 911 calls, emergency medical
      services, timely triage and transport to acute care, and transfer to
      rehabilitation services. Substantial progress has been made in establishing
      statewide trauma systems, which are seen as the prototype for regionalized care
      for other time-sensitive, emergency conditions such as stroke. Trauma systems
      provide a model of care that is consistent with the goals of the Affordable Care
      Act, which authorizes $100 million in annual grants to ensure the continued
      availability of trauma services. Full funding of these provisions is needed to
      stabilize statewide systems that are struggling to survive. We describe the
      components of a regionalized trauma system, review the evidence in support of
      this approach, and discuss the challenges to sustaining systems that are
      accountable and affordable. 

PMID- 24301392
TI  - Dispelling an urban legend: frequent emergency department users have substantial
      burden of disease.
AB  - Urban legend has often characterized frequent emergency department (ED) patients
      as mentally ill substance users who are a costly drain on the health care system
      and who contribute to ED overcrowding because of unnecessary visits for
      conditions that could be treated more efficiently elsewhere. This study of
      Medicaid ED users in New York City shows that behavioral health conditions are
      responsible for a small share of ED visits by frequent users, and that ED use
      accounts for a small portion of these patients' total Medicaid costs. Frequent ED
      users have a substantial burden of disease, and they have high rates of primary
      and specialty care use. They also have linkages to outpatient care that are
      comparable to those of other ED patients. It is possible to use predictive
      modeling to identify who will become a repeat ED user and thus to help target
      interventions. However, policy makers should view reducing frequent ED use as
      only one element of more-comprehensive intervention strategies for frequent
      health system users. 

PMID- 24301393
TI  - Emergency care for children in the United States.
AB  - A formal emergency care system for children in the United States began in the
      1980s with the establishment of specialized training programs in academic
      children's hospitals. The ensuing three decades have witnessed the establishment
      of informal regional networks for clinical care and a federally funded research
      consortium that allows for multisite research on evidence-based practices.
      However, pediatric emergency care suffers from problems common to emergency
      departments (EDs) in general, which include misaligned incentives for care,
      overcrowding, and wide variation in the quality of care. In pediatric emergency
      care specifically, there are problems with low-volume EDs that have neither the
      experience nor the equipment to treat children, poor adherence to clinical
      guidelines, lack of resources for mental health patients, and a lack of widely
      accepted performance metrics. We call for policies to address these issues,
      including providing after-hours care in other settings and restructuring payment
      and reimbursement policies to better address patients' needs. 

PMID- 24301394
TI  - Transforming emergency care for older adults.
AB  - Already crowded and stressful, US emergency departments (EDs) are facing the
      challenge of serving an aging population that requires complex and lengthy
      evaluations. Creative solutions are necessary to improve the value and ensure the
      quality of emergency care delivered to older adults while more fully addressing
      their complex underlying physical, social, cognitive, and situational needs.
      Developing models of geriatric emergency care, including some that are already in
      use at dedicated geriatric EDs, incorporate a variety of physical, procedural,
      and staffing changes. Among the options for "geriatricizing" emergency care are
      approaches that may eliminate the need for an ED visit, such as telemedicine; for
      initial hospitalization, such as patient observation units; and for
      rehospitalization, such as comprehensive discharge planning. By transforming
      their current safety-net role to becoming a partner in care coordination, EDs
      have the opportunity to become better integrated into the broader health care
      system, improve patient health outcomes, contribute to optimizing the health care
      system, and reduce overall costs of care-keys to improving emergency care for
      patients of all ages. 

PMID- 24301395
TI  - A promising approach for emergency departments to care for patients with
      substance use and behavioral disorders.
AB  - Millions of patients visit US emergency departments (EDs) each year because of
      substance use and behavioral disorders. Caring for these people is daunting,
      given the high patient volumes and increasing acuity of illness that EDs are
      experiencing. The nation's primary care system has limited capacity to treat
      these individuals, who are often uninsured, poor, and sick. A growing body of
      evidence suggests that screening, providing a brief intervention, and referring
      these patients to treatment-an approach known as SBIRT-can be effective in the
      ED. Typically requiring just five to ten minutes, SBIRT incorporates principles
      of motivational interviewing, an evidence-based counseling technique that uses
      empathy, positive framing, reflective listening, and gentle education to
      encourage people to change risky behavior. This article describes what is known
      about the clinical and cost-effectiveness of SBIRT when applied to ED patients
      with substance use and behavioral disorders. The article recommends adopting
      SBIRT broadly to help EDs become a coordinated part of the health care system,
      offering opportunities to improve the health of millions of Americans. 

PMID- 24301396
TI  - Quality measurement in the emergency department: past and future.
AB  - As the United States seeks to improve the value of health care, there is an
      urgent need to develop quality measurement for emergency departments (EDs). EDs
      provide 130 million patient visits per year and are involved in half of all
      hospital admissions. Efforts to measure ED quality are in their infancy, focusing
      on a small set of conditions and timeliness measures, such as waiting times and
      length-of-stay. We review the history of ED quality measurement, identify policy
      levers for implementing performance measures, and propose a measurement agenda.
      Initial priorities include measures of effective care for serious conditions that
      are commonly seen in EDs, such as trauma; measures of efficient use of resources,
      such as high-cost imaging and hospital admission; and measures of diagnostic
      accuracy. More research is needed to support the development of measures of care
      coordination and regionalization and the episode cost of ED care. Policy makers
      can advance quality improvement in ED care by asking ED researchers and
      organizations to accelerate the development of quality measures of ED care and
      incorporating the measures into programs that publicly report on quality of care
      and incentive-based payment systems. 

PMID- 24301397
TI  - A public-private trauma center network in Florida harnesses data to improve care
      quality for an aging population.
AB  - As the US population ages, trauma systems face new challenges in addition to the
      long-standing problem of access. Patients ages sixty-five and older are more
      likely than younger patients to fall and suffer serious injury or death as a
      result. This older patient population, when compared with younger cohorts,
      suffers higher mortality rates, has more comorbidities-diabetes, cancer, and
      heart conditions being the more serious among them-and takes more medications,
      which can complicate treatment. The University of South Florida (USF) Medical
      School and the HCA hospital system have partnered to create a network of five
      trauma centers in underserved areas of the state to increase access to trauma
      care for all Floridians while maintaining a special focus on geriatric trauma
      care. Collecting and analyzing data for improving care quality and undertaking
      research is a central aim of the partnership. Based on their research findings,
      trauma surgeons in the USF/HCA Trauma Network have identified best practices and
      codified them in standard operating procedures. 

PMID- 24301398
TI  - Giving EMS flexibility in transporting low-acuity patients could generate
      substantial Medicare savings.
AB  - Some Medicare beneficiaries who place 911 calls to request an ambulance might
      safely be cared for in settings other than the emergency department (ED) at lower
      cost. Using 2005-09 Medicare claims data and a validated algorithm, we estimated
      that 12.9-16.2 percent of Medicare-covered 911 emergency medical services (EMS)
      transports involved conditions that were probably nonemergent or primary care
      treatable. Among beneficiaries not admitted to the hospital, about 34.5 percent
      had a low-acuity diagnosis that might have been managed outside the ED. Annual
      Medicare EMS and ED payments for these patients were approximately $1 billion per
      year. If Medicare had the flexibility to reimburse EMS for managing selected 911
      calls in ways other than transport to an ED, we estimate that the federal
      government could save $283-$560 million or more per year, while improving the
      continuity of patient care. If private insurance companies followed suit, overall
      societal savings could be twice as large. 

PMID- 24301399
TI  - Protocol-driven emergency department observation units offer savings, shorter
      stays, and reduced admissions.
AB  - Many patients who seek emergency department (ED) treatment are not well enough
      for immediate discharge but are not clearly sick enough to warrant full inpatient
      admission. These patients are increasingly treated as outpatients using
      observation services. Hospitals employ four basic approaches to observation
      services, which can be categorized by the presence or absence of a dedicated
      observation unit and of defined protocols. To understand which approach might
      have the greatest impact, we compared 2010 data from three sources: a case study
      of observation units in Atlanta, Georgia; statewide discharge data for Georgia;
      and national survey and discharge data. Compared to patients receiving
      observation services elsewhere in the hospital, patients cared for in "type 1"
      observation units-dedicated units with defined protocols-have a 23-38 percent
      shorter length-of-stay, a 17-44 percent lower probability of subsequent inpatient
      admission, and $950 million in potential national cost savings each year.
      Furthermore, we estimate that 11.7 percent of short-stay inpatients nationwide
      could be treated in a type 1 unit, with possible savings of $5.5-$8.5 billion
      annually. Policy makers should have hospitals report the setting in which
      observation services are provided and consider payment incentives for care in a
      type 1 unit. 

PMID- 24301400
TI  - Strategies for integrating cost-consciousness into acute care should focus on
      rewarding high-value care.
AB  - The acute care system reflects the best and worst in American medicine. The
      system, which includes urgent care and retail clinics, emergency departments,
      hospitals, and doctors' offices, delivers 24/7 care for life-threatening
      conditions and is a key part of the safety net for the under- and uninsured. At
      the same time, it is fragmented, disconnected, and costly. We describe strategies
      to contain acute care costs. Reducing demands for acute care may be achieved
      through public health measures and educational initiatives; in contrast, delivery
      system reform has shown mixed results. Changing providers' behavior will require
      the development of care pathways, assessments of goals of care, and practice
      feedback. Creating alternatives to hospitalization and enhancing the
      interoperability of electronic health records will be key levers in cost
      containment. Finally, we contend that fee-for-service with modified payments
      based on quality and resource measures is the only feasible acute care payment
      model; others might be so disruptive that they could threaten the system's
      effectiveness and the safety net. 

PMID- 24301401
TI  - The US emergency care system: meeting everyday acute care needs while being ready
      for disasters.
AB  - The emergency care system is an essential part of the US health care system. In
      addition to providing acute resuscitation and life- and limb-saving care, the
      emergency care system provides considerable support to physicians outside the
      emergency department and serves as an important safety-net provider. In times of
      disaster, the emergency care system must be able to surge rapidly to accommodate
      a massive influx of patients, sometimes with little or no notice. Extreme daily
      demands on the system can promote innovations and adaptations that are invaluable
      in responding to disasters. However, excessive and inappropriate utilization is
      wasteful and can diminish "surge capacity" when it is most needed. Certain
      features of the US health care system have imposed strains on the emergency care
      system. We explore policy issues related to moving toward an emergency care
      system that can more effectively meet both individuals' needs for acute care and
      the broader needs of the community in times of disaster. Strategies for the
      redesign of the emergency care system must include the active engagement of both
      patients and the community and a close look at how to align incentives to reward
      quality and efficiency throughout the health care system. 

PMID- 24301402
TI  - Learning from Japan: strengthening US emergency care and disaster response.
AB  - As Hurricane Katrina demonstrated in 2005, US health response systems for
      disasters-typically designed to handle only short-term mass-casualty events-are
      inadequately prepared for disasters that result in large-scale population
      displacements. Similarly, after the 2011 Great East Japan Earthquake, Japan found
      that many of its disaster shelters failed to meet international standards for
      long-term provision of basic needs and health care for the vulnerable populations
      that sought refuge in the shelters. Hospital disaster plans had not been tested
      and turned out to be inadequate, and emergency communication equipment did not
      function. We make policy recommendations that aim to improve US responses to mass
      displacement disasters based on Japan's 2011 experience. First, response systems
      must provide for the extended care of large populations of chronically ill and
      vulnerable people. Second, policies should ensure that shelters meet or exceed
      international standards for the provision of food, water, sanitation, and
      privacy. Third, hospital disaster plans should include redundant communication
      systems and sufficient emergency provisions for both staff and patients. Finally,
      there must be routine drills for responses to mass-displacement disasters so that
      areas needing improvement can be uncovered before an emergency occurs. 

PMID- 24301403
TI  - On constant alert: lessons to be learned from Israel's emergency response to mass
      casualty terrorism incidents.
AB  - In its short modern history, Israel has had to contend with numerous mass
      casualty incidents caused by terrorism. As a result, it has developed practical
      national preparedness policies for responding to such events. Israel's Supreme
      Health Authority, a committee of the Ministry of Health, coordinates emergency
      management nationwide. All emergency personnel, health care providers, and
      medical facilities operate under national policies designed to ensure a swift and
      coordinated response to any incident, based on an "all hazards" approach that
      emphasizes core elements commonly encountered in mass-casualty incidents.
      Israel's emergency management system includes contingency planning, command and
      control, centrally coordinated response, cooperation, and capacity building.
      Although every nation is unique, many of the lessons that Israel has learned may
      be broadly applicable to preparation for mass-casualty incidents in the United
      States and other countries. 

PMID- 24301404
TI  - NIH: developing and funding research in emergency care and training the next
      generation of emergency care researchers.
AB  - For the best health care to be provided in emergency settings, it must be based
      on the best available science. There are about 136 million visits to emergency
      departments (EDs) in the United States annually. Many of the nation's most
      critically ill patients are first stabilized and treated in EDs-the point of
      origin for nearly half of all medical intensive care unit admissions and a fourth
      of all surgical intensive care unit admissions. This article explores the role of
      the National Institutes of Health (NIH) in developing and funding research in
      emergency care and in training the next generation of emergency care researchers.
      Recognizing that effective emergency care research spans multiple organ systems
      and disciplines, the NIH established the Office of Emergency Care Research in
      December 2011 to facilitate and coordinate funding opportunities relevant to
      research and research training in emergency settings. Because the NIH funds
      education, basic research, and large clinical trials, it plays a key role in
      improving emergency care. 

PMID- 24301405
TI  - Health information exchange improves identification of frequent emergency
      department users.
AB  - We hypothesized that using communitywide data from a health information exchange
      (HIE) could improve the ability to identify frequent emergency department (ED)
      users-those with four or more ED visits in thirty days-by allowing ED use to be
      measured across unaffiliated hospitals. When we analyzed HIE-wide data instead of
      site-specific data, we identified 20.3 percent more frequent ED users (5,756
      versus 4,785) and 16.0 percent more visits by them to the ED (53,031 versus
      45,771). Additionally, we found that 28.8 percent of frequent ED users visited
      multiple EDs during the twelve-month study period, versus 3.0 percent of all ED
      users. All three differences were significant ($$p ). An improved ability to
      identify frequent ED users allows better targeting of case management and other
      services that can improve frequent ED users' health and reduce their use of
      costly emergency medical services. 

PMID- 24301406
TI  - A resident helps redesign how one institution provides emergency care.

PMID- 24301409
TI  - The impact of nurse staffing on readmissions.

PMID- 24301410
TI  - Staffing and readmissions: the authors reply.

PMID- 24301411
TI  - Train physicians right the first time--in residency.

PMID- 24301412
TI  - Incentives to participate in wellness programs.

PMID- 24301413
TI  - The multidimensionality of peer pressure in adolescence.
AB  - A sample of 689 adolescents (grades 7-12) from two Midwestern communities who had
      been identified by peers as members of one of three major peer groups responded
      to a self-report survey measuring perceptions of peer pressure in five areas of
      behavior: involvement with peers, school involvement, family involvement,
      conformity to peer norms, and misconduct. Perceived pressures toward peer
      involvement were particularly strong, whereas peer pressures concerning
      misconduct were relatively ambivalent. Perceived pressures toward misconduct
      increased across grade levels and pressures to conform to peer norms diminished;
      grade differences in perceived peer pressures concerning family involvement were
      community specific. Compared to druggie-toughs, jock-populars perceived stronger
      peer pressures toward school and family involvement, and less pressure toward
      (stronger pressure against) misconduct; patterns of perceived pressure among
      loners were more variable across communities. Results elaborated the process of
      peer influence in adolescent socialization and identity development. 

PMID- 24301414
TI  - Using panel data to examine sex differences in causal relationships among
      adolescent alcohol use, norms, and peer alcohol use.
AB  - This paper uses longitudinal data and multiple regression of follow-up data on
      baseline data to identify direction of causality among adolescent alcohol use,
      normative structure toward alcohol, and peer alcohol use. Baseline and follow-up
      data were collected on a random sample of 100 adolescents (54 males). Separate
      regressions were performed on male and female respondents. Among males, self
      drinking and normative structure toward alcohol were found to have a reciprocal
      relationship over time. No significant relationship was found between self and
      peer alcohol use over time among males. Among females, close-friend alcohol use
      was found to be causally prior to self drinking and other-friend drinking level.
      Normative structure toward alcohol was found unrelated to other variables over
      time among females. 

PMID- 24301415
TI  - Alcohol: The gateway to other drug use among secondary-school students.
AB  - The "stepping-stone" theory of progression into drug use is examined, based on
      the alcohol and other drug use of over 27,000 seventh-through eighth-grade
      students in New York State. The data show that students do not use illicit drugs
      unless they also use alcohol. White, black and Hispanic students all tend to
      initiate the use of drugs in the following order-alcohol, marijuana, pills, and
      "hard" drugs. Among blacks and Hispanics, pills are not as important a transition
      between marijuana and hard drugs as they are among whites. Cigarettes form an
      important step between alcohol and marijuana use for younger students,
      particularly for females. Since alcohol serves as the gateway to all other drug
      use, prevention approaches that control and limit alcohol use among adolescents
      may be warranted. 

PMID- 24301416
TI  - Peers, parents, and adolescent drug use in a rural community: A two-wave panel
      study.
AB  - This study examined the relative influence of changes in orientations to ward
      peers and parents on the drug-use patterns of a panel of rural youths. It was
      hypothesized that, when the changes in orientations that occurred over a three
      year period of time were evaluated, the level of involvement with either alcohol
      or marijuana would be highest for those youths experiencing movement toward
      positions sympathetic to the use of drugs. The data analysis revealed that after
      three years there was greater distance between youths and their parents on the
      subject of drugs, and that those youths who experienced the greatest movement
      were also the most heavily involved with drugs. The single best predictor of the
      use rate for either type of drug was the level of past use, followed by changes
      in the level of drug-related conflict with parents. Among the peer-based
      measures, changes in the frequency of both pro- and antidrug-use discussions were
      found to make a significant contribution only in the case of marijuana use. 

PMID- 24301417
TI  - Effects of group intervention on moral development of distressed youths in
      Israel.
AB  - The effects of a positive peer culture (PPC) program [H. H. Vorrath and L. K.
      Brendatro (1974),Positive Peer Culture, Aladin, Chicago, Illinois] upon the moral
      development of "youths in distress" within the framework of streetcorner gangs
      was measured. This group was compared with two control groups, one related and
      the other unrelated to the participants. Moraldevelopment measures used in this
      study-resistance to temptation, moral stage, feeling after offense, punishment,
      and confession [A. Ziv (1976), Measuring aspects of morality.J. Moral Educ. 5:
      189-201]-indicated a positive effect upon the participants, and for some moral
      indices, on their friends' moral development (the related group). The potential
      effect upon moral development of such a program and the possibility of working
      with representatives of youth-in-distress groups in order to produce change are
      stressed. 

PMID- 24301418
TI  - Diffusion within Marcia's identity-status paradigm: Does it foreshadow academic
      problems?
AB  - The present investigation attempted to ascertain longitudinally whether
      diffuseness about academic goals and plans would predict subsequent
      underachievement. Identity-status interviews were administered to 98
      firstsemester college students. Their grade point averages (GPA) were obtained
      for their first six semesters in college. SAT and conceptual-level scores were
      used to generate predicted GPAs. Underachievement was operationally defined as a
      positive discrepancy between predicted-minus-observed GPA:
      underachievement=predicted observed GPA. Evidence for the hypothesized
      relationship between diffusion and academic underachievement was not found. To
      the contrary, Diffusions during their freshman year showed a tendency for
      relativeoverachievement (predicted observed GPA). The possibility of
      heterogeneity within Marcia's diffusion status was considered. Some diffuselike
      individuals may see their current lack of commitment and concern as a hiatus,
      whereas others may be truly unconcerned and myopic about their lives. A
      significant association between foreclosure and underachievement was found when
      the subjects were freshmen. This relationship was not replicated with an
      independent sample of 90 high school students. A post hoc interpretation focused
      on differences between transient and long-term Foreclosures and the role that the
      college environment may potentially play in instigating personal identity crises.
      The need for longitudinal tests on this account is underscored. 

PMID- 24301419
TI  - Monitoring low-radioactivity caesium in Fukushima waters.
AB  - A new monitoring system has been established to assess low-level radioactive
      caesium in Fukushima waters directly using caesium adsorbents: plastic
      containers, U8 containers, and a germanium (Ge) detector container packed with
      nanoparticle-Prussian blue (PB) immobilized on a polymer. The results show that
      the calibration coefficient for a flow rate of 0.3 L min(-1) was 1.27 in
      Fukushima waters for germanium semiconductor scintillations related to (133)Cs
      concentrations and radioactive caesium amounts. 

PMID- 24301420
TI  - Metastatic melanoma to the liver: a contemporary and comprehensive review of
      surgical, systemic, and regional therapeutic options.
AB  - Effective management of hepatic metastases from ocular and cutaneous melanoma
      remains a major therapeutic challenge. Treatment options include hepatic
      resection, hepatic intra-arterial (HIA) chemotherapy, chemoembolization, and
      hepatic perfusions. Evaluating the efficacy of these interventions is limited by
      the retrospective nature of most of the data, although controlled phase 3 studies
      are starting to emerge. Studies of hepatic resection are strongly suggestive of a
      survival benefit following surgery in selected patients. Effective systemic
      agents for metastatic cutaneous melanoma are available and supported by
      randomized controlled phase 3 trials. In contrast, no active systemic treatment
      has yet been identified for metastatic ocular melanoma. HIA and intravenous
      delivery of fotemustine have been compared in a randomized phase 3 trial in
      patients with unresectable metastases from melanoma, but no differences between
      the 2 approaches were observed. Hepatic arterial chemoembolization appears only
      to be moderately effective according to uncontrolled studies; targeting patients
      with less liver involvement may improve outcomes. A recent phase 3 study showed a
      significant improvement in hepatic progression-free survival with percutaneous
      hepatic perfusion compared with best alternative care in patients with metastatic
      melanoma; however, the overall survival analysis was confounded by crossover of
      control patients to active treatment. In conclusion, hepatic resection offers the
      possibility of long-term survival in carefully selected patients with liver
      limited metastases from melanoma. In patients with unresectable cutaneous
      melanoma, effective systemic therapy is the best treatment option. For patients
      with unresectable ocular melanoma, regional treatments are likely to assume a
      greater role until effective systemic treatments are identified.

PMID- 24301421
TI  - Asymmetric dimethylarginine and augmentation index in newly diagnosed patients
      with hypertension.
AB  - Pulse wave velocity (PWV), augmentation index (Aix), and central aortic pressure
      (CAP) are arterial stiffness markers of endothelial dysfunction (ED). We
      investigated the relationship between arterial stiffness parameters and
      asymmetric dimethylarginine (ADMA; a marker of ED), in newly diagnosed patients
      with hypertension (n = 101; 61 females). These patients were investigated in
      accordance with the recommendations of hypertension guidelines. Arterial
      stiffness was measured, and serum ADMA and C-reactive protein (CRP; a marker of
      inflammation) levels were determined. In both women and men, there was no
      difference in terms of age, body mass index, systolic and diastolic blood
      pressures, PWV, CAP and the levels of ADMA, while Aix and CRP levels were
      significantly higher in women (P = .004, P = .046, respectively). In the whole
      group, ADMA levels correlated with Aix (Pearson r = .237, P = .024). Our findings
      provide further evidence of a link between arterial stiffness and ED in newly
      diagnosed patients with hypertension. 

PMID- 24301422
TI  - Predictive value of admission platelet volume indices for in-hospital major
      adverse cardiovascular events in acute ST-segment elevation myocardial
      infarction.
AB  - Although mean platelet volume (MPV) is an independent correlate of impaired
      angiographic reperfusion and 6-month mortality in ST-segment elevation myocardial
      infarction (STEMI) treated with primary percutaneous coronary intervention
      (pPCI), there is less data regarding the association between platelet
      distribution width (PDW) and in-hospital major adverse cardiovascular events
      (MACEs). A total of 306 patients with STEMI pPCI were evaluated. No reflow was
      defined as a post-PCI thrombolysis in myocardial infarction (TIMI) flow grade of
      0, 1, or 2 (group 1). Angiographic success was defined as TIMI flow grade 3
      (group 2). The values of MPV and PDW were higher among patients with no reflow.
      In-stent thrombosis, nonfatal myocardial infarction, in-hospital mortality, and
      MACEs were significantly more frequent among patients with no reflow. In
      multivariate analysis, PDW, MPV, high-sensitivity C-reactive protein, and glucose
      on admission were independent correlates of in-hospital MACEs. Admission PDW and
      MPV are independent correlates of no reflow and in-hospital MACEs among patients
      with STEMI undergoing pPCI. 

PMID- 24301423
TI  - Prevalence of microalbuminuria among middle-aged population of China: a multiple
      center cardiovascular epidemiological study.
AB  - We assessed the prevalence of microalbuminuria (MAU) and the relationships with
      other cardiovascular (CV) risk factors among a middle-aged Chinese population.
      Data from 10 313 participants were included in our cross-sectional survey.
      Microalbuminuria was defined as the urine albumin to creatinine ratio of 30:300
      mg/g from a single-spot morning urine sample. Microalbuminuria was found to be
      common in males and females (15.04% vs 10.09%) aged 35 to 64 years in this
      Chinese general population, especially in those with obesity, hypertension, and
      diabetes. Multivariate analysis found that body mass index, triglyceride, high
      sensitivity C-reactive protein, alcohol consumption, hypertension, and diabetes
      were independently associated with MAU. Microalbuminuria may be a useful
      indicator for risk of CV disease in general populations. 

PMID- 24301424
TI  - Glucose levels and depression in Hispanic patients admitted to the cardiovascular
      intensive care unit: a cross-sectional study.
AB  - Depression is frequently associated with diabetes mellitus (DM) and may worsen DM
      related morbidity and mortality. We determined the potential association of
      glucose levels with depression in Hispanic patients admitted to the
      Cardiovascular Intensive Care Unit. Patients were given the Center for
      Epidemiologic Studies-Depression scale survey within 24 hours of admission.
      Glycated hemoglobin and fasting blood glucose levels within 30 days of admission
      were extracted. The HbA1c levels remained significantly associated with both
      presence of depression and depression levels. Histories of DM, myocardial
      infarction, and percutaneous coronary intervention as well as baseline brain
      natriuretic peptide levels were also significantly associated with depression
      levels. The presence of a significant association between glucose levels and
      depression in Hispanic patients indicates that there is a need for optimal
      management of glycemic levels. This may then lead to better health outcomes in
      Hispanics with cardiovascular disease. 

PMID- 24301425
TI  - Endothelial function and Behcet disease.

PMID- 24301426
TI  - Centralized pan-Middle East Survey on the undertreatment of hypercholesterolemia:
      results from the CEPHEUS study in Arabian Gulf countries.
AB  - The Centralized pan-Middle East Survey on the undertreatment of
      hypercholesterolemia (CEPHEUS) survey evaluated the attainment of low-density
      lipoprotein cholesterol (LDL-C) goals among patients on lipid-lowering drugs
      (LLDs) according to the updated National Cholesterol Education Program (NCEP)
      Adult Treatment Panel (ATP-III) guideline. The survey was conducted in 6 Arabian
      Gulf countries. Patients aged >=18 years on LLDs for at least >=3 months (stable
      medication for >=6 weeks) were recruited. Fasting blood samples were collected at
      a single visit. In this survey, 5276 (58.2% male) patients were included in the
      final analysis. The LDL-C goal was attained in 91.1% of low-risk, 52.7% of high
      risk, and 32.0% in very-high-risk categories. Goal attainment was directly
      related to female gender, age<40 years, history of diabetes, and family history
      of cardiovascular disease. The results of this survey highlight the suboptimal
      management of hypercholesterolemia across Arabian Gulf countries.

PMID- 24301427
TI  - Highly sensitive determination of new metabolite in rat plasma after oral
      administration of swertiamarin by liquid chromatography/time of flight mass
      spectrometry following picolinoyl derivatization.
AB  - The metabolism of swertiamarin (STM) in vivo was studied by LC/MS following
      picolinoyl derivatization. Incubation of erythrocentaurin (ECR), one of the main
      in vitro metabolites of STM by intestinal bacteria, with liver microsome
      indicated that STM may be metabolized to the final metabolite 3,4-dihydro-5
      (hydroxymethyl) isochroman-1-one (HMIO) in vivo. After hydrolyzation with
      sulfatase, HMIO was successfully detected in rat plasma after oral administration
      of STM by LC/MS following picolinoyl derivatization. 4-Methoxyphenyl methanol was
      used as the internal standard to quantify HMIO in rat plasma. The full metabolic
      pathway of STM in rats is proposed. STM is first hydrolyzed by bacterial beta
      glucusidase to give aglycone, which is readily converted to ECR and nitrogen
      containing metabolite. ECR is further reduced to HMIO by both liver and
      intestinal bacteria and HMIO is finally converted to the new sulfate conjugate
      metabolite. The monoterpene compound STM was found to be metabolized to
      dihydroisocoumarin and alkaloid compounds in vivo, which may be responsible for
      the pharmacological effect of STM. The results may shed light on clinical
      efficacy of STM and the new analytical method developed may assist in studies of
      the metabolism of other natural iridoids and secoiridoids in vivo.

PMID- 24301428
TI  - Development and reliability testing of the Comprehensive High-Level Activity
      Mobility Predictor (CHAMP) in male servicemembers with traumatic lower-limb loss.
AB  - The opportunity for wounded servicemembers (SMs) to return to high-level activity
      and return to duty has improved with advances in surgery, rehabilitation, and
      prosthetic technology. As a result, there is now a need for a high-level mobility
      outcome measure to assess progress toward high-level mobility during and after
      rehabilitation. The purpose of this study was to develop and determine the
      reliability of a new outcome measure called the Comprehensive High-Level Activity
      Mobility Predictor (CHAMP). The CHAMP consists of the Single Limb Stance, Edgren
      Side Step Test, T-Test, and Illinois Agility Test. CHAMP reliability was
      determined for SMs with lower-limb loss (LLL) (interrater: n = 118; test-retest:
      n = 111) and without LLL ( n = 97). A linear system was developed to combine the
      CHAMP items and produce a composite score that ranges from 0 to 40, with higher
      scores indicating better performance. Interrater and test-retest intraclass
      correlation coefficient values for the CHAMP were 1.0 and 0.97, respectively. A
      CHAMP score equal to or greater than 33 points is within the range for SMs
      without LLL. The CHAMP was found to be a safe and reliable measure of high-level
      mobility in SMs with traumatic LLL. 

PMID- 24301429
TI  - Construct validity of Comprehensive High-Level Activity Mobility Predictor
      (CHAMP) for male servicemembers with traumatic lower-limb loss.
AB  - This study examined the convergent construct validity of a new performance-based
      assessment instrument called the Comprehensive High-Level Activity Mobility
      Predictor (CHAMP) as a measure of high-level mobility in servicemembers (SMs)
      with traumatic lower-limb loss (LLL). The study was completed by 118 SMs.
      Convergent construct validity of the CHAMP was established using the 6-minute
      walk test (6MWT) as a measure of overall mobility and physical function and the
      Amputee Mobility Predictor (AMP) as a measure of basic prosthetic mobility. The
      known group methods construct validity examined disparities in high-level
      mobility capability among SMs with different levels of LLL. The CHAMP score
      demonstrated a strong positive relationship between 6MWT distance (r = 0.80, p <
      0.001) and AMP score (r = 0.87, p < 0.001), respectively. In addition, the CHAMP
      can discriminate between different levels of LLL. Study findings support the
      CHAMP as a valid performance-based assessment instrument of high-level mobility
      for SMs with traumatic LLL. 

PMID- 24301430
TI  - Comparison of 6-minute walk test performance between male Active Duty soldiers
      and servicemembers with and without traumatic lower-limb loss.
AB  - The rehabilitation of U.S. military servicemembers (SMs) who have sustained a
      traumatic loss of one or both lower limbs requires outcome measures that can
      assess their physical capabilities in comparison with their uninjured colleagues.
      Describing reference ranges for the 6-minute walk test (6MWT) in both populations
      will help clinicians develop appropriate goals for rehabilitation and document
      progress toward those goals. A convenience sample of 118 male U.S. SMs with and
      97 without traumatic lower-limb loss participated in this study. All participants
      completed a 6MWT, and comparisons were made between SMs with and without limb
      loss and among the levels of limb loss. The SMs without lower-limb loss performed
      significantly better than all SMs with lower-limb loss. The SMs with transtibial
      limb loss performed significantly better than those with all other levels of limb
      loss. Statistically significant and clinically relevant differences were also
      noted between the other levels of limb loss. No differences were found between
      different prosthetic components. Reference ranges were established for U.S. SMs
      with and without various levels of limb loss, and the 6MWT was able to identify
      functional differences between groups. 

PMID- 24301431
TI  - Comparison between microprocessor-controlled ankle/foot and conventional
      prosthetic feet during stair negotiation in people with unilateral transtibial
      amputation.
AB  - Contrary to stance-phase dorsiflexion of conventional prosthetic feet, the
      microprocessor-controlled Proprio foot permits swing-phase dorsiflexion on
      stairs. The purpose of this study was to compare Symmetry in External Work (SEW)
      between a microprocessor-controlled foot and conventional prosthetic feet in two
      groups with unilateral transtibial amputation (Medicare Functional Classification
      Levels K-Level-2 and K-Level-3) during stair ascent and descent. Ten subjects
      were evaluated while wearing three conventional prosthetic feet- solid ankle
      cushion heel (SACH), stationary attachment flexible endoskeleton (SAFE), and
      Talux-and the Proprio foot using a study socket and were given a 10- to 14-day
      accommodation period with each foot. Ground reaction forces were collected using
      F-scan sensors during stair ascent and descent. The SEW between the intact and
      amputated limbs was calculated for each foot. During stair ascent, the Proprio
      foot resulted in a higher interlimb symmetry than conventional prosthetic feet,
      with significant differences between the Pro prio and SACH/SAFE feet. The swing
      phase dorsiflexion appeared to promote greater interlimb symmetry because it
      facilitated forward motion of the body, resulting in a heel-to-toe center of
      pressure trajectory. During stair descent, all feet had low symmetry without
      significant differences between feet. The movement strategy used when descending
      stairs, which is to roll over the edge of a step, had a greater influence on
      symmetry than the dorsiflexion features of prosthetic feet. 

PMID- 24301432
TI  - Comparison of three agility tests with male servicemembers: Edgren Side Step
      Test, T-Test, and Illinois Agility Test.
AB  - Performance-based outcomes such as the T-Test, Edgren Side Step Test (ESST), and
      Illinois Agility Test (IAT) have been used to assess agility in athletes and
      nonathletes; however, the reliability and validity of these tests have not been
      established. The purpose of this study was to establish the reliability and
      convergent construct validity of the ESST, T-Test, and IAT in young, nondisabled,
      physically active male servicemembers (SMs). Ninety-seven male Active Duty U.S.
      Army SMs completed the study. Statistically significant differences were not
      found between the ESST (p = 0.10), T-Test (p = 0.09), and IAT (p = 0.23) when
      administered twice within a 24 to 48 h period. These tests were found to have
      excellent interrater reliability and moderate to good test-retest reliability. A
      good positive relationship exists between the IAT and T-Test (r = 0.76, p <
      0.001) and a moderate negative relationship exists between the ESST and both the
      T-Test (r = -0.69, p < 0.001) and IAT (r = -0.65, p < 0.001). The results suggest
      that these tests are valid measures of agility that uniquely assess movement in
      different planes, thus providing a comprehensive assessment of high-level
      mobility. 

PMID- 24301433
TI  - Amputee mobility predictor-bilateral: a performance-based measure of mobility for
      people with bilateral lower-limb loss.
AB  - The Amputee Mobility Predictor (AMP) is an outcome measure designed to assess
      mobility and functional capabilities for people with unilateral lower-limb
      amputation. No comparable measure exists for those with bilateral lower-limb
      amputation (BLLA). The purpose of this study was to examine the utility of the
      AMP-Bilateral (AMP-B) to measure the ability to perform functional tasks related
      to participation in advanced skill activities in those with BLLA and to determine
      whether AMP-B scores correlated with 6-minute walk test (6MWT) performance.
      Twenty-six male servicemembers (SMs) completed the study: 12 with bilateral
      transtibial amputation (BTTA), 7 with bilateral transfemoral amputation (BTFA),
      and 7 with combination transtibial and transfemoral amputation (TTA/TFA).
      Significant differences existed between the AMP-B scores (p < 0.001), AMP scores
      (p < 0.001), and 6MWT distance (p < 0.05) for SMs with BTTA and TTA/TFA and SMs
      with BTTA and BTFA but not between those with BTFA and TTA/TFA. Scoring of five
      AMP items was modified because they necessitate at least one intact knee joint to
      generate the necessary torque requirements to perform the activity without upper
      limb assistance. Minor modifications in scoring of the AMP do not alter total
      score and allow clinicians to determine the mobility and functional capabilities
      of SMs with BTFA and TFA/TTA. 

PMID- 24301434
TI  - Factors related to high-level mobility in male servicemembers with traumatic
      lower-limb loss.
AB  - The purpose of this study was to examine the possible relationship between
      factors modifiable by rehabilitation interventions (rehabilitation factors),
      other factors related to lower-limb loss (other factors), and high-level mobility
      as measured by the Comprehensive High-Level Activity Mobility Predictor (CHAMP)
      in servicemembers (SMs) with traumatic lower-limb loss. One-hundred eighteen male
      SMs with either unilateral transtibial amputation (TTA), unilateral transfemoral
      amputation (TFA), or bilateral lower-limb amputation (BLLA) participated.
      Stepwise regression analysis was used to develop separate regression models of
      factors predicting CHAMP score. Regression models containing both rehabilitation
      factors and other factors explained 81% (TTA), 36% (TFA), and 91% (BLLA) of the
      variance in CHAMP score. Rehabilitation factors such as lower-limb strength and
      dynamic balance were found to be significantly related to CHAMP score and can be
      enhanced with the appropriate intervention. Further, the findings support the
      importance of salvaging the knee joint and its effect on high-level mobility
      capabilities. Lastly, the J-shaped energy storage and return feet were found to
      improve high-level mobility for SMs with TTA. These results could help guide
      rehabilitation and aid in developing appropriate interventions to assist in
      maximizing high-level mobility capabilities for SMs with traumatic lower-limb
      loss. 

PMID- 24301435
TI  - Effects of 660 nm low-level laser therapy on muscle healing process after
      cryolesion.
AB  - The aim of this study was to evaluate the effects of 660 nm low-level laser
      therapy (LLLT) on muscle regeneration after cryolesion in rat tibialis anterior
      muscle. Sixty-three Wistar rats were divided into a control group, 10 J/cm(2)
      laser-treated group, and 50 J/cm(2) laser-treated group. Each group formed three
      subgroups (n = 7 per group), and the animals were sacrificed 7, 14, or 21 d after
      lesion. Histopathological findings revealed a lower inflammatory process in the
      laser-treated groups after 7 d. After 14 d, irradiated animals at both fluences
      showed higher granulation tissue, new muscle fibers, and organized muscle
      structure. After 21 d, full tissue repair was observed in all groups. Moreover,
      irradiated animals at both fluences showed smaller necrosis area in the first
      experimental period evaluated. MyoD immunoexpression was observed in both treated
      groups 7 d postinjury. Myogenin immunoexpression was detected after 7 and 14 d.
      The higher fluence increased the number of blood vessels after 14 and 21 d. These
      results suggest that LLLT, at both fluences, positively affects injured skeletal
      muscle in rats, accelerating the muscle-regeneration process. 

PMID- 24301436
TI  - OtoID: new extended frequency, portable audiometer for ototoxicity monitoring.
AB  - Portability of equipment is an increasingly important component in the practice
      of audiology. We report on a new device, the OtoID, that supports evidence-based
      ototoxicity testing protocols, provides capability for hearing testing on the
      hospital treatment unit, and can automate patient self-testing. The purpose of
      this article is to report on the validation and verification of the OtoID
      portable audiometer in 40 subjects both young and old, with and without hearing
      impairment. Subjects were evaluated by an audiologist using the manual hearing
      test program and then self-tested via an automated testing program. Testing was
      done in a sound booth and on a hospital treatment unit. Therefore, data were
      collected in four conditions (booth vs hospital unit and automated vs manual
      testing) and analyzed for testing bias, repeatability, and American Speech
      Language-Hearing Association-significant ototoxicity false-positive rate.
      Repeatable hearing threshold results were obtained on all subjects who performed
      the test, regardless of hearing status or testing location. 

PMID- 24301437
TI  - Influence of prior activity on residual limb volume and shape measured using
      plaster casting: results from individuals with transtibial limb loss.
AB  - The purpose of this research was to determine whether prior activity affected the
      shape of a plaster cast taken of a transtibial residual limb. Plaster casts were
      taken twice on one day in 24 participants with transtibial limb loss, with 5 s
      between doffing and casting in one trial (PDI-5s) and 20 min in the other trial
      (PDI-20m). The ordering of the trials was randomized. The mean +/- standard
      deviation radial difference between PDI-20m and PDI-5s was 0.34 +/- 0.21 mm when
      PDI-5s was conducted first and -0.02 +/- 0.20 mm when PDI-20m was conducted
      first. Ordering of the trials had a statistically significant influence on the
      mean radial difference between the two shapes (p = 0.008). The result shows that
      prior activity influenced the residual limb cast shape. Practitioners should be
      mindful of prior activity and doffing history when casting an individual's limb
      for socket design and prosthetic fitting. 

PMID- 24301438
TI  - Evaluation of scooters using ANSI/RESNA standards.
AB  - To date, only one research study has evaluated how scooters respond to static and
      dynamic stability. However, no other studies have evaluated how scooters respond
      to adverse conditions and how they perform in all standard tests. A selection of
      12 three-wheeled scooters was tested according to American National Standards
      Institute/Rehabilitation Engineering and Assistive Technology Society of North
      America (ANSI/ RESNA) wheelchair standards. Scooter models included the Victory,
      Gogo, Golden Companion (GC) I, and GC II. Victory and GC II were the most stable
      scooters. The Gogo scooters were the least dynamically stable. Five scooters (3
      Gogo, 1 GC I, 1 GC II) failed the environmental condition tests. All GC I and II
      scooters failed parts of the power and control system tests. All scooters passed
      static and impact tests; however, all Gogo scooters and one GC II scooter had
      structural or motor failure during durability tests. The scooter models' survival
      life ranged from 62,512 to 1,178,230 cycles out of the 400,000 needed to pass the
      test. Tiller failures (typically tiller tube snapping) occurred with an average
      of 1,483 N force applied to the tiller structure. Our results indicate that these
      commercially available devices may not meet ANSI/RESNA standards. In addition,
      the tiller test should be conducted with scooters to further ensure their safety
      and durability and should use a test dummy with weight capacity according to the
      mobility device capacity. 

PMID- 24301439
TI  - Prolonged electrical stimulation-induced gluteal and hamstring muscle activation
      and sitting pressure in spinal cord injury: effect of duty cycle.
AB  - Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury
      (SCI). Electrical stimulation (ES) activates muscles and might reduce risk
      factors. Our objectives were to study and compare the effects of two duty cycles
      during 3 h of ES-induced gluteal and hamstring activation on interface pressure
      distribution in sitting individuals with SCI and study the usability of a newly
      developed electrode garment (ES shorts). Ten individuals with SCI participated in
      this study, in which two ES protocols with different duty cycles (1:1 s vs 1:4 s
      on-off) were applied in counterbalanced order using a custom-made garment with
      built-in electrodes. Outcome variables included interface pressure of the ischial
      tuberosities (ITs) and pressure gradient. A questionnaire was used to determine
      usability of the ES shorts. In both protocols, ES caused a significant decrease
      in average IT pressure compared with rest (no ES); on average, 35% for protocol
      1:4 and 13% for protocol 1:1. The ES on-off duty cycle of protocol 1:4 showed
      less muscle fatigue. In general, participants scored the usability of the ES
      shorts as satisfactory. In this study, the application of ES resulted in a
      significant decrease in IT pressure. The ES on-off duty cycle of 1:4 s is
      recommended because of the less fatiguing effect. ES of the hamstrings and
      gluteal muscles might be a promising method in preventing PUs, but further study
      is needed. 

PMID- 24301440
TI  - More than the final score: development, application, and future research of
      comprehensive high-level activity mobility predictor.

PMID- 24301441
TI  - Implementing outcome measures-the military physical therapist's perspective.

PMID- 24301442
TI  - Developing and testing a new outcome measure.

PMID- 24301443
TI  - Induction of haploidy from pollen grains in angiosperms - the current status.
AB  - Since the successful induction of haploids from anthers cultured in vitro in
      1964, a great deal of attention has been given to this problem by those
      interested in obtaining pure lines and mutants for crop improvement and
      biochemical genetics. In the last 16 years the anther culture technique has been
      refined and extended to over one hundred and fifty different species. More
      recently, isolated pollen culture - which is a refinement of the original anther
      culture technique - has also been developed. In this review we have made an
      effort to critically examine existing reports with the objective of analysing the
      effects of various factors - e.g. culture medium, the cultural conditions, and
      the effect of genotype and physiological state of the parent plant on pollen
      induction - and to speculate on the mechanism of action of different factors in
      order to throw some light on the process of haploid induction. 

PMID- 24301444
TI  - Low calving rates in Brahman cross cattle.
AB  - It is suggested that the low calving rate of crosses between Bos taurus cows and
      Brahman bulls in the F2 generation, in later generations and in breeds derived
      from the cross, could be due to the difference between the Bos taurus Y and the
      Bos indicus Y if this difference is due to a translocation between the Y and an
      autosome. It is suggested that such a translocation could set up a balanced
      polymorphism and perpetuate low calving rates against selection. 

PMID- 24301445
TI  - Chromosomal location of the catalase structural genes in Zea mays using B-A
      translocations.
AB  - B-A translocations have been used to map the catalase genes, Cat1, Cat2, and Cat3
      of Zea mays. Cat1 was found to be on the short arm of chromosome 5, 9.1 map units
      from brittle endosperm (bt 1). Cat2 was located on chromosome 1S, while Cat3 was
      located on the distal half of chromosome 1L. There was no linkage between Cat2
      and Cat3. The significance of mapping the catalase structural genes is discussed.

PMID- 24301446
TI  - Cytoplasmic DNA variation and relationships in cereal genomes.
AB  - Chloroplast (cp) and mitochondrial (mt) DNAs were isolated from four cereal
      genomes (cultivated wheat, rye, barley and oats) and compared by restriction
      nuclease analysis. Cleavage of cp and mt DNAs by Sal I, Kpn I, Xho I and EcoR I
      enzymes indicated that each cereal group contains specific cytoplasmic DNAs. A
      phylogenetic tree of cereal evolution has been obtained on the basis of cp DNA
      homologies. It is suggested that wheat and rye diverged after their common
      ancestor had diverged from the ancestor of barley. This was preceded by the
      divergence of the common ancestor of wheat, rye and barley and the ancestor of
      oats.The molecular weight of the different cp DNAs was determined from the Sal I
      and Kpn I patterns. cp DNAs from wheat, rye, barley and oats appeared to be
      characterized by a very similar molecular weight of about 80-82.10(6) d.In the
      case of the mt DNAs, the great number of restriction fragments obtained with the
      restriction enzymes used prevented precise comparisons and determination of
      molecular weights. 

PMID- 24301447
TI  - Hereditary variability of plants under the action of exogenous DNA.
AB  - Injection of exogenous barley donor DNA into grains of barley recipient plants at
      the milk maturity stage, with a specially designed syringe, led to the appearance
      of transformed plants. The transformation (in rare cases) was caused by the
      unsheared DNA since the DNA passing through the syringe needle remained
      relatively stable (10(6) to 10(7) daltons) as was confirmed by DNA sedimentation
      analysis.14 plants grown from seeds injected with highly polymeric DNA containing
      close to 30 per cent protein had transformed pollen grains. In the 2nd generation
      only 2 plants from the 8 studied preserved these changes. In the progeny of these
      two plants, i.e., in the 3rd seed generation after injection, 82.1 per cent of
      plants preserved the transformed characters. The next, 4th generation, preserved
      a transformed phenotype in 89.6 per cent of plants.It was also shown that
      reversion to a recipient-like state was not always constant. We found the
      reversion of transformed properties (i.e., normal starch and two-rowed spikes) in
      40 per cent of the 4th generation descendants of one of the plants which had lost
      the phenotypical expression of these properties in the 3rd generation but had
      them in the 2nd generation.The study of the morphological properties of
      transformed plants showed that with respect to phenotypic expression some
      characters were changed towards the donor type, some remained as in the
      recipients and some were of the intermediate type. 

PMID- 24301448
TI  - Genotype dependent radiosensitivity of autotetraploids in Trigonella foenum
      graecum L.
AB  - Different diploids of Trigonella foenum-graecum L. and their corresponding
      autotetraploids were seed-treated with 40 krad of gamma-rays, and parameters such
      as germination, survival, growth reduction, pollen fertility, pod setting, etc.
      were recorded. A stimulation of seed germination due to the irradiation could be
      observed. Contrary to the general rule that polyploids are more radioresistant
      than their corresponding diploids, one 4x strain was completely killed while the
      2x version survived comparatively well. Apparently gene reduplication is not the
      overall protective mechanism as was once earlier believed. The importance of
      genotypic influence on radiosensitivity was demonstrated at both the 2x and 4x
      level. The limitation of interphase chromosome volume and degree of ploidy in
      predicting radiosensitivity is discussed. 

PMID- 24301449
TI  - Guest editor's introduction: Social support and risk reduction.

PMID- 24301450
TI  - Social support and well-being: Implications for prevention programs.
AB  - A variety of prevention programs have assumed that social support has health
      promotive and health-protective effects. Although numerous studies have examined
      the relationship between social support and well-being, the result has been a
      heterogeneous and complex set of findings. We seek to review and summarize this
      research as a data base for planning and evaluating prevention programs. To
      organize our review, we present a model of stress, support, and well-being which
      distinguishes among several mechanisms through which support may affect well
      being. We consider research on each of these mechanisms: thedirect effects of
      support upon functioning; theindirect effects of support upon functioning through
      its influence on exposure to environmental stressors; and theinteractive effects
      of social support in buffering the individual from the maladaptive effects of
      stress. We then address several implications of this research that need to be
      considered in the process of designing and evaluating prevention programs: (a)
      the need to consider the varying mechanisms through which social support has its
      effects; (b) the need for specificity in developing preventive interventions; and
      (c) the need to examine relationships among stress, support, and functioning
      within a broader social context. 

PMID- 24301451
TI  - An analysis of the effectiveness of parent-infant support groups.
AB  - A variety of programs have been developed to provide support and education for
      new parents. This article analyzes underlying issues in, and common problems of,
      parent-infant support groups. The Family Development Parenting Groups are
      described to illustrate typical findings of very positive feelings of
      participants toward the groups, but few objective effects of participation on
      adjustment or family functioning. The analysis suggests the importance of
      coordinating the type of goals of the program with (a) the needs of participants;
      (b) the implementation strategies; and (c) the measurement of positive and
      negative effects. The need to clarify the operationalization of support and to
      specifically measure the behavioral processes and effects of support is
      emphasized. 

PMID- 24301452
TI  - The helping network approach: Community promotion of mental health.
AB  - The Galt Helping Network Project was a two-year program to augment mental health
      and community services in a rural California community through the use of natural
      or informal resources. The experiment made use of a preventive intervention model
      which identified important needs of local youth and families, board and care
      residents, the entire community for recreation and for mental health services,
      and the Mexican American Community for recognition and participation. It brought
      a number of volunteers into the provision of direct services and created a number
      of institutional forms by which continued services and enlarged voluntary
      participation in community affairs are continuing beyond the official end of the
      project. This article concludes that the Galt Helping Network Model can provide a
      major contribution to mental health maintenance and community involvement through
      the recognition of natural helpers and the involvement of the community in an
      active form of problem solving. Through these methods a community with limited
      fiscal resources can take a major step toward providing a caring and helping
      environment for its members. 

PMID- 24301453
TI  - The Elder Program: A strategy for prevention.

PMID- 24301454
TI  - The approach of social ecology: A partnership of support and empowerment.

PMID- 24301455
TI  - Semiparametric tests for identifying differentially methylated loci with case
      control designs using Illumina arrays.
AB  - DNA methylation plays an important role in the development of many types of
      cancer. Identifying differentially methylated loci between cancer and normal
      patients is one of the central tasks to understand the contributions of the
      methylation process on cancer development. Through investigation of the
      methylation measurements generated by the Illumina methylation arrays, we notice
      that the methylation measurements of the cancer and normal groups could differ
      not only in means but also in variances. Therefore, we propose a generalized
      exponential tilt model to capture the differences in both means and variances
      between the cancer and normal groups. We derive the semiparametric tests to
      obtain model robustness. Through simulation studies, we demonstrate the
      feasibility of the proposed tests and a much improved power of the proposed tests
      than that of the t-test and the regression-based tests when the cancer and normal
      groups are different in variances only or in both means and variances. Hence the
      proposed tests can serve as useful complements to the standard tests that only
      test differences in means. We also illustrate the proposed methods by applying to
      a real methylation data from a recent study on ovarian cancer where the proposed
      methods identified additional methylation loci that were missed by the existing
      method. 

PMID- 24301456
TI  - Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from
      the ESPAC-3 trial.
AB  - BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in
      pancreatic adenocarcinoma may predict survival in patients who receive adjuvant
      gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to
      chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained
      with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high
      hENT1 expression if the mean H score for their cores was above the overall median
      H score (48). High and low hENT1-expressing groups were compared using Kaplan
      Meier curves, log-rank tests, and Cox proportional hazards models. All
      statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%)
      and 1808 cores were suitable and included in the final analysis. Median overall
      survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence
      interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for
      176 patients treated with 5-fluorouracil/folinic acid (chi(2) 1=0.24; P = .62).
      Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to
      23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4)
      months for those with high hENT1 expression (chi(2)1= 9.87; P = .002). For the 5
      fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9
      (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression,
      respectively (chi(2)1 = 0.83; P = .36). hENT1 levels were not predictive of
      survival for the 28 patients of the observation group (chi(2)1 = 0.37; P = .54).
      Multivariable analysis confirmed hENT1 expression as a predictive marker in
      gemcitabine-treated (Wald chi(2) = 9.16; P = .003) but not 5-fluorouracil-treated
      (Wald chi(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective
      validation, gemcitabine should not be used for patients with low tumor hENT1
      expression.

PMID- 24301459
TI  - ERRATUM.

PMID- 24301457
TI  - Role of CYB5A in pancreatic cancer prognosis and autophagy modulation.
AB  - BACKGROUND: Loss of 18q22.3 is a prognostic marker in pancreatic ductal
      adenocarcinoma (PDAC). This study investigated genes encoded by this cytoband.
      METHODS: We studied mRNA/protein expression in radically resected (n = 130) and
      metastatic patients (n = 50). The role of CYB5A was tested in 11 PDAC cell lines
      and five primary cultures through retrovirus-mediated upregulation and small
      interfering RNA using wound-healing, invasion, annexin-V, electron microscopy,
      and autophagic assays, as well as autophagy genes and kinases arrays. CYB5A+
      orthotopic models (n = 6 mice/group) were monitored by Firefly and Gaussia
      luciferase bioluminescence, magnetic resonance imaging, and high-frequency
      ultrasound. Data were analyzed by t test, Fisher exact-test, log-rank test and
      Cox proportional hazards models. All statistical tests were two-sided. RESULTS:
      Both resected and metastatic patients with low mRNA or protein expression of
      CYB5A had statistically significantly shorter survival (eg, median = 16.7 months,
      95% confidence interval [CI] = 13.5 to 19.9; vs median = 24.8 months, 95% CI =
      12.8 to 36.9; P = .02, two-sided log-rank test; n = 82 radically resected PDACs),
      and multivariable analyses confirmed prognostic relevance. Moreover, we
      characterized a novel function to CYB5A, autophagy induction, concomitant with
      reduced proliferation and migration/invasion of PDAC cells. Network analysis of
      proautophagic pathways suggested CYB5A interaction with TRAF6, which was
      confirmed by TRAF6 downregulation after CYB5A reconstitution (-69% in SU.86.86
      CYB5A+; P = .005, two-sided t test). CYB5A silencing had opposite effects,
      restoring TRAF6 expression and wound healing. In vivo studies showed that CYB5A
      induced autophagy while inhibiting tumor growth/metastasis and increasing
      survival (median = 57 days, 95% CI = 52 to 61; vs median = 44 days, 95% CI = 21
      to 57; P = .03, two-sided log-rank test). CONCLUSIONS: These results define CYB5A
      as a novel prognostic factor for PDAC that exerts its tumor-suppressor function
      through autophagy induction and TRAF6 modulation.

PMID- 24301460
TI  - Overcoming ultraviolet light instability of sensitized TiO2 with meso
      superstructured organometal tri-halide perovskite solar cells.
AB  - The power conversion efficiency of hybrid solid-state solar cells has more than
      doubled from 7 to 15% over the past year. This is largely as a result of the
      incorporation of organometallic trihalide perovskite absorbers into these
      devices. But, as promising as this development is, long-term operational
      stability is just as important as initial conversion efficiency when it comes to
      the development of practical solid-state solar cells. Here we identify a critical
      instability in mesoporous TiO2-sensitized solar cells arising from light-induced
      desorption of surface-adsorbed oxygen. We show that this instability does not
      arise in mesoporous TiO2-free mesosuperstructured solar cells. Moreover, our TiO2
      free cells deliver stable photocurrent for over 1,000 h continuous exposure and
      operation under full spectrum simulated sunlight.

PMID- 24301461
TI  - Factors associated with early recurrence and death after esophagectomy for
      cancer.
AB  - BACKGROUND: Accurate selection of patients for radical treatment of esophageal
      cancer is essential to avoid early recurrence and death (ERD) after surgery. We
      sought to evaluate a large series of consecutive resections to assess factors
      that may be associated with this poor outcome. METHODS: This was a cohort study
      including 680 patients operated for esophageal cancer between 2000 and 2010. The
      poor outcome group comprised 100 patients with tumor recurrence and death within
      1 year of surgery. The comparison group comprised 267 long-term survivors,
      defined as those surviving more than 3 years from surgery. Pathological
      characteristics associated with poor outcome were analyzed using logistic
      regression to determine odds ratios (OR) and 95% confidence intervals (CI).
      RESULTS: On the adjusted model T stage and N stage predicted poor survival, with
      the greatest risk being patients with locally advanced tumors and three or more
      involved lymph nodes (OR 10.6, 95% CI 2.8-40.0). Poor differentiation (OR 2.8,
      95% CI 1.4-5.5), chemotherapy response (OR 3.6, 95% CI 1.2-10.6), and involved
      resection margins (OR 2.7, 95% CI 1.2-6.0) were all significant independent
      prognostic markers in the multivariable model. There was a trend toward worse
      survival with lymphovascular invasion (OR 2.0, 95% CI 0.9-4.2) and low albumin
      (OR 1.9, 95% CI 0.8-4.4) but not of statistical significance in the adjusted
      model. CONCLUSIONS: Esophageal cancer patients with poorly differentiated tumors
      and three or more involved lymph nodes have a particularly high risk of ERD after
      surgery. Accurate risk stratification of patients may identify a group who would
      be better served by alternative oncological treatment strategies.

PMID- 24301462
TI  - Cross-talk between E. coli strains and a human colorectal adenocarcinoma-derived
      cell line.
AB  - Although there is great interest in the specific mechanisms of how gut microbiota
      modulate the biological processes of the human host, the extent of host-microbe
      interactions and the bacteria-specific metabolic activities for survival in the
      co-evolved gastrointestinal environment remain unclear. Here, we demonstrate a
      comprehensive comparison of the host epithelial response induced by either a
      pathogenic or commensal strain of Escherichia coli using a multi-omics approach.
      We show that Caco-2 cells incubated with E. coli display an activation of defense
      response genes associated with oxidative stress. Indeed, in the bacteria co
      culture system, the host cells experience an altered environment compared with
      the germ-free system that includes reduced pH, depletion of major energy
      substrates, and accumulation of fermentation by-products. Measurement of
      intracellular Caco-2 cell metabolites revealed a significantly increased lactate
      concentration, as well as changes in TCA cycle intermediates. Our results will
      lead to a deeper understanding of acute microbial-host interactions. 

PMID- 24301463
TI  - Conveying principles of embryonic development by metaphors from daily life.
AB  - How can the revolution in our understanding of embryonic development and stem
      cells be conveyed to the general public? Here, I present a photographic approach
      to highlight scientific concepts of pattern formation using metaphors from daily
      life, displaying pairs of images of embryonic development and the corresponding
      human analogy. By making the viewer 'feel' like a cell within a developing
      embryo, the personal experiences resonate with the scientific concepts,
      facilitating a new type of appreciation. 

PMID- 24301464
TI  - Mechanisms of scaling in pattern formation.
AB  - Many organisms and their constituent tissues and organs vary substantially in
      size but differ little in morphology; they appear to be scaled versions of a
      common template or pattern. Such scaling involves adjusting the intrinsic scale
      of spatial patterns of gene expression that are set up during development to the
      size of the system. Identifying the mechanisms that regulate scaling of patterns
      at the tissue, organ and organism level during development is a longstanding
      challenge in biology, but recent molecular-level data and mathematical modeling
      have shed light on scaling mechanisms in several systems, including Drosophila
      and Xenopus. Here, we investigate the underlying principles needed for
      understanding the mechanisms that can produce scale invariance in spatial pattern
      formation and discuss examples of systems that scale during development. 

PMID- 24301465
TI  - The Xenopus homologue of Down syndrome critical region protein 6 drives
      dorsoanterior gene expression and embryonic axis formation by antagonising
      polycomb group proteins.
AB  - Mesoderm and embryonic axis formation in vertebrates is mediated by maternal and
      zygotic factors that activate the expression of target genes. Transcriptional
      derepression plays an important role in the regulation of expression in different
      contexts; however, its involvement and possible mechanism in mesoderm and
      embryonic axis formation are largely unknown. Here we demonstrate that XDSCR6, a
      Xenopus homologue of human Down syndrome critical region protein 6 (DSCR6, or
      RIPPLY3), regulates mesoderm and embryonic axis formation through derepression of
      polycomb group (PcG) proteins. Xdscr6 maternal mRNA is enriched in the endoderm
      of the early gastrula and potently triggers the formation of dorsal mesoderm and
      neural tissues in ectoderm explants; it also dorsalises ventral mesoderm during
      gastrulation and induces a secondary embryonic axis. A WRPW motif, which is
      present in all DSCR6 homologues, is necessary and sufficient for the dorsal
      mesoderm- and axis-inducing activity. Knockdown of Xdscr6 inhibits dorsal
      mesoderm gene expression and results in head deficiency. We further show that
      XDSCR6 physically interacts with PcG proteins through the WRPW motif, preventing
      the formation of PcG bodies and antagonising their repressor activity in
      embryonic axis formation. By chromatin immunoprecipitation, we demonstrate that
      XDSCR6 releases PcG proteins from chromatin and allows dorsal mesoderm gene
      transcription. Our studies suggest that XDSCR6 might function to sequester PcG
      proteins and identify a novel derepression mechanism implicated in embryonic
      induction and axis formation. 

PMID- 24301466
TI  - A new role for the calcineurin/NFAT pathway in neonatal myosin heavy chain
      expression via the NFATc2/MyoD complex during mouse myogenesis.
AB  - The calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway is
      involved in the modulation of the adult muscle fiber type, but its role in the
      establishment of the muscle phenotype remains elusive. Here, we show that the
      NFAT member NFATc2 cooperates with the basic helix-loop-helix transcription
      factor MyoD to induce the expression of a specific myosin heavy chain (MHC)
      isoform, the neonatal one, during embryogenesis. We found this cooperation to be
      crucial, as Myod/Nfatc2 double-null mice die at birth, with a dramatic reduction
      of the major neonatal MHC isoform normally expressed at birth in skeletal
      muscles, such as limb and intercostal muscles, whereas its expression is
      unaffected in myofibers mutated for either factor alone. Using gel shift and
      chromatin immunoprecipitation assays, we identified NFATc2 bound to the neonatal
      Mhc gene, whereas NFATc1 and NFATc3 would preferentially bind the embryonic Mhc
      gene. We provide evidence that MyoD synergistically cooperates with NFATc2 at the
      neonatal Mhc promoter. Altogether, our findings demonstrate that the
      calcineurin/NFAT pathway plays a new role in establishing the early muscle fiber
      type in immature myofibers during embryogenesis. 

PMID- 24301468
TI  - Phosphine-catalyzed domino reaction: a novel sequential [2+3] and [3+2]
      annulation reaction of gamma-substituent allenoates to construct bicyclic[3, 3,
      0]octene derivatives.
AB  - We have successfully developed a novel and efficient phosphine-catalyzed
      sequential [2+3] and [3+2] annulation reaction of gamma-substituent allenoates to
      construct bicyclic[3, 3, 0]octene derivatives. The protocol uses readily
      available gamma-substituent allenoates as the starting materials, inexpensive
      PBu3 as the catalyst, and the corresponding products were obtained in good to
      excellent yields under mild conditions. 

PMID- 24301469
TI  - The long-term effects of phage concentration on the inhibition of planktonic
      bacterial cultures.
AB  - Since the early 1920s there has been an interest in using bacteriophages (phages)
      for the control of bacterial pathogens. While there are many factors that have
      limited the success of phage bio-control, one particular problem is the
      variability of outcomes between phages and bacteria. Specifically, there is a
      significant need for a better understanding of how initial phage concentrations
      affect long-term bacterial inhibition. In work reported herein three phages were
      isolated for Escherichia coli K12, Pseudomonas aeruginosa PAO1, as well as
      Bacillus cereus and bio-control experiments were performed with phage
      concentrations ranging from 10(5) to 10(8) plaque forming units per mL over the
      course of 72 h. For four of the nine phages isolated there was a linear
      relationship between inhibition and phage concentration, suggesting the effect of
      phage concentration is important at longer time scales. For three of the isolated
      phages, phage concentrations had no effect on bacterial inhibition suggesting
      that even at the lowest concentration the method of action was saturated and
      lower concentrations might still be effective. Additionally, a cocktail was
      created and was compared to the previously isolated phages. There was no
      statistical difference between the cocktail and the best performing phage
      highlighting the importance of selecting the appropriate phages for treatment.
      These results suggest that, for certain phages, there is a strong relationship
      between phage concentration and long-term bacterial growth inhibition and the
      initial phage concentration is an important indicator of the long-term outcome. 

PMID- 24301467
TI  - Different CHD chromatin remodelers are required for expression of distinct gene
      sets and specific stages during development of Dictyostelium discoideum.
AB  - Control of chromatin structure is crucial for multicellular development and
      regulation of cell differentiation. The CHD (chromodomain-helicase-DNA binding)
      protein family is one of the major ATP-dependent, chromatin remodeling factors
      that regulate nucleosome positioning and access of transcription factors and RNA
      polymerase to the eukaryotic genome. There are three mammalian CHD subfamilies
      and their impaired functions are associated with several human diseases. Here, we
      identify three CHD orthologs (ChdA, ChdB and ChdC) in Dictyostelium discoideum.
      These CHDs are expressed throughout development, but with unique patterns. Null
      mutants lacking each CHD have distinct phenotypes that reflect their expression
      patterns and suggest functional specificity. Accordingly, using genome-wide (RNA
      seq) transcriptome profiling for each null strain, we show that the different
      CHDs regulate distinct gene sets during both growth and development. ChdC is an
      apparent ortholog of the mammalian Class III CHD group that is associated with
      the human CHARGE syndrome, and GO analyses of aberrant gene expression in chdC
      nulls suggest defects in both cell-autonomous and non-autonomous signaling, which
      have been confirmed through analyses of chdC nulls developed in pure populations
      or with low levels of wild-type cells. This study provides novel insight into the
      broad function of CHDs in the regulation development and disease, through
      chromatin-mediated changes in directed gene expression. 

PMID- 24301470
TI  - Cuticular hydrocarbons regulate mate recognition, male aggression, and female
      choice of the rove beetle,Aleochara curtula.
AB  - Immature, starved, or multiply mated males of the staphylinid beetle,Aleochara
      curtula, mimic their females chemically. The titer of the female sex pheromone
      components (Z)-7-heneicosene and (Z)-7-tricosene was quantified for various
      physiological types and both sexes by gas chromatography and correlated with the
      sexual response of males towards the cuticular hydrocarbon fractions. Modulation
      of intermale aggression by production of the female pheromone was shown by (1)
      reduction of the alkene titer of females kept at elevated temperatures, (2)
      treating live males with the synthetic female pheromone mixture, and (3) gradual
      amputation of male antennal segments.A. curtula males do not fight against
      members of otherAleochara species with a different hydrocarbon pattern.
      Contamination ofA. peschkei males with the hydrocarbon fraction ofA. curtula
      males, however, provoked the release of aggression. Choosy females reject mating
      attempts of males bearing the female sex pheromone. 

PMID- 24301471
TI  - Interactions of alkaloids with galeal chemosensory cells of colorado potato
      beetle.
AB  - The galeal chemosensory system of the adult Colorado potato beetle was used as a
      model to study the effects of alkaloids on insect gustation. Nine alkaloids,
      representing a wide range of structural types, were used. Their ability to
      stimulate chemosensory cells when presented in isolation and their ability to
      interfere with normal chemosensory processes were emphasized. None of the
      alkaloids stimulated chemosensory cells in a dose-dependent manner, although a
      few stimulated low-level activity from some cells. There was no evidence for a
      general "deterrent receptor" in these beetles. Some of the alkaloids had a marked
      inhibitory effect on normal chemosensory responses. Tomatine, solanine,
      papaverine, and sparteine significantly inhibited responses to amino acids
      (represented by GABA) while quinine and papaverine inhibited responses to
      sucrose. An attempt was made to correlate neurophysiological action of some
      alkaloids with their effects on feeding behavior. It was clear from this
      correlation that even a dramatic inhibition of sensory input by an alkaloid does
      not necessarily lead to measurable effects on behavior. The results are discussed
      in the context of current theories on the mode of action of alkaloids and other
      secondary plant compounds which may be involved in host recognition by
      phytophagous insects. 

PMID- 24301472
TI  - Effects of double-bond configuration on interaction between a moth sex pheromone
      component and its receptor : A receptor-interaction model based on molecular
      mechanics.
AB  - The dependence of the electrophysiological activity on the change of double-bond
      configuration of (Z)-5-decenyl acetate, a pheromone component of the turnip
      moth,Agrotis segetum, and a dienic analog, (E)-2,(Z)-5-decadienyl acetate, have
      been investigated by single-cell measurements and molecular mechanics
      calculations (MM2). A previously reported model for the interaction between a
      moth sex pheromone component and its receptor has been refined. This new model
      gives an essentially quantitative correlation between the measured activities and
      the calculated conformational energies for a biologically active conformation
      defined by the model. Previously obtained structure-activity results for chain
      elongated analogs of (Z)-5-decenyl acetate are significantly improved by the
      refined model. The effect of a change of the double-bond configuration on the
      substrate-receptor interaction is not additive but depends on the conformational
      properties of the entire molecule. 

PMID- 24301473
TI  - Coumarins inPrunus mahaleb and its herbivore, the small ermine mothYponomeuta
      mahalebellus.
AB  - Larvae of the small ermine mothYponomeuta mahalebellus were reared on foliage
      ofPrunus mahaleb, a plant known to contain coumarins. Thin-layer chromatography
      and gas chromatography showed that coumarin, umbelliferone, and herniarin were
      present in leaves ofP. mahaleb and in pupae and adults ofY. mahalebellus. Overall
      concentrations of simple coumarins in the plant and insect were, respectively,
      0.54% and 0.003-0.004% (dry weight). The possible role of coumarins in the
      chemical defense of both the plant and insect is discussed. 

PMID- 24301475
TI  - Turnover of the D1 protein and of Photosystem II in a Synechocystis 6803 mutant
      lacking Tyrz.
AB  - The Photosystem II reaction center is rapidly inactivated by light, particularly
      at higher light intensity. One of the possible factors causing this phenomenon is
      the oxidized primary donor, P680(+), which may be harmful to Photosystem II
      because of its highly oxidizing nature. However, no direct evidence specificially
      implicating P680(+) in photoinhibition has been obtained yet. To investigate
      whether P680(+) is harmful to Photosystem II, turnover of the D1 protein and of
      the Photosystem II reaction center complex were measured in vivo in a mutant of
      the cyanobacterium Synechocystis sp. PCC 6803, in which the physiological donor
      to P680(+), Tyrz, was genetically deleted. In this mutant, D1 degradation in the
      light is an order of magnitude faster than in wild type. The most straightforward
      explanation of this phenomenon is that accumulation of P680(+) leads to an
      increased rate of turnover of the Photosystem II reaction center complex, which
      is compatible with the hypothesis of destructive oxidation by P680(+) that is
      damaging to the Photosystem II complex. 

PMID- 24301474
TI  - Chilling-enhanced photooxidation: The production, action and study of reactive
      oxygen species produced during chilling in the light.
AB  - Chilling-enhanced photooxidation is the light- and oxygen-dependent bleaching of
      photosynthetic pigments that occurs upon the exposure of chilling-sensitive
      plants to temperatures below approximately 10  degrees C. The oxidants
      responsible for the bleaching are the reactive oxygen species (ROS) singlet
      oxygen ((1)O2), superoxide anion radical (O 2 (?) ,hydrogen peroxide (H2O2), the
      hydroxyl radical (OH.), and the monodehydroascorbate radical (MDA) which are
      generated by a leakage of absorbed light energy from the photosynthetic electron
      transport chain. Cold temperatures slow the energy-consuming Calvin-Benson Cycle
      enzymes more than the energy-transducing light reactions, thus causing leakage of
      energy to oxygen. ROS and MDA are removed, in part, by the action of antioxidant
      enzymes of the Halliwell/Foyer/Asada Cycle. Chloroplasts also contain high levels
      of both lipid- and water-soluble antioxidants that act alone or in concert with
      the HFA Cycle enzymes to scavenge ROS. The ability of chilling-resistant plants
      to maintain active HFA Cycle enzymes and adequate levels of antioxidants in the
      cold and light contributes to their ability to resist chilling-enhanced
      photooxidation. The absence of this ability in chilling-sensitive species makes
      them susceptible to chilling-enhanced photooxidation. Chloroplasts may reduce the
      generation of ROS by dissipating the absorbed energy through a number of
      quenching mechanisms involving zeaxanthin formation, state changes and the
      increased usage of reducing equivalents by other anabolic pathways found in the
      stroma. During chilling in the light, ROS produced in chilling-sensitive plants
      lower the redox potential of the chloroplast stroma to such a degree that
      reductively-activated regulatory enzymes of the Calvin Cycle, sedohepulose 1,7
      bisphosphatase (EC 3.1.3.37) and fructose 1,6 bisphosphatase (EC 3.1.3.11), are
      oxidatively inhibited. This inhibition is reversible in vitro with a DTT
      treatment indicating that the enzymes themselves are not permanently damaged. The
      inhibition of SBPase and FBPase may fully explain the inhibition in whole leaf
      gas exchange seen upon the rewarming of chilling-sensitive plants chilled in the
      light. Methods for the study of ROS in chilling-enhanced photooxidation and
      challenges for the future are discussed. 

PMID- 24301476
TI  - 5-O-beta-D-galactopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin, an
      inhibitor of photophosphorylation in spinach chloroplasts.
AB  - 5-O-beta-D-galactopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin isolated
      from Exostema caribaeum (Rubiaceae) has been found to act as an energy-transfer
      inhibitor in spinach chloroplasts. ATP synthesis and phosphorylating (coupled)
      electron flow were inhibited by 89 and 72%, respectively, at a concentration of
      400 MUM. H(+)-uptake, basal and uncoupled electron transport were not affected by
      the coumarin. The light-activated Mg(+2)-ATPase activity from bound membrane
      thylakoid chloroplasts was slightly inhibited by the coumarin. Also, the heat
      activated Ca(+2)-ATPase activity of the isolated coupling factor protein was
      insensitive to this compound. In chloroplasts partially stripped of coupling
      factor 1 by an EDTA treatment, the coumarin showed a restoration of the proton
      uptake process. These results suggest that the 4-phenylcoumarin under
      investigation inhibited phosphorylation in chloroplasts by specifically blocking
      the transport of protons through a membrane-bound component or a carrier channel
      (CFO) located in a hydrophobic region at or near the functional binding site for
      the coupling factor 1. 

PMID- 24301477
TI  - The interactive effects of elevated CO2 and O 3 concentration on photosynthesis
      in spring wheat.
AB  - This study investigated the interacting effects of carbon dioxide and ozone on
      photosynthetic physiology in the flag leaves of spring wheat (Triticum aestivum
      L. cv. Wembley), at three stages of development. Plants were exposed throughout
      their development to reciprocal combinations of two carbon dioxide and two ozone
      treatments: [CO2] at 350 or 700 MUmol mol(-1), [O3] at < 5 or 60 nmol mol(-1).
      Gas exchange analysis, coupled spectrophotometric assay for RuBisCO activity, and
      SDS-PAGE, were used to examine the relative importance of pollutant effects on i)
      stomatal conductance, ii) quantum yield, and iii) RuBisCO activity, activation,
      and concentration. Independently, both elevated [CO2] and elevated [O3] caused a
      loss of RuBisCO protein and Vcmax. In combination, elevated [CO2] partially
      protected against the deleterious effects of ozone. It did this partly by
      reducing stomatal conductance, and thereby reducing the effective ozone dose.
      Elevated [O3] caused stomatal closure largely via its effect on
      photoassimilation. 

PMID- 24301478
TI  - Kinetic interactions of glycine with substrates and effectors of
      phosphenolpyruvate carboxylase from maize leaves.
AB  - Glycine enhanced the sensitivity of maize phosphenolpyruvate carboxylase to the
      activator glucose 6-phosphate and reduced the sensitivity of the enzyme to the
      inhibitors malate and aspartate. The effects of glycine on the kinetic constants
      for these other effectors were greater than its effect on the Km for substrate,
      raising the Ki(malate) 11-fold and reducing Ka(glucose6-P) 7-fold, while reducing
      the Km(PEP) by 3-fold. Kinetically saturating levels of glycine and glucose 6
      phosphate acted synergistically to raise Ki(malate) higher than that observed
      with either activator alone. Glycine and glucose 6-phosphate also synergistically
      reduced aspartate inhibition. Dual inhibitor analysis indicated that aspartate
      and malate bind in a mutually exclusive manner, and thus probably compete for the
      same inhibitor site. In contrast, the synergism between glycine and glucose 6
      phosphate indicate that these activators bind at separate sites. Glycine also
      reduced the Km(Mg) by 3-fold but had no significant effect on the Km of
      bicarbonate. 

PMID- 24301479
TI  - The donor side of Photosystem II as the copper-inhibitory binding site :
      Fluorescence and polarografic studies.
AB  - We have measured, under Cu (II) toxicity conditions, the oxygen-evolving capacity
      of spinach PS II particles in the Hill reactions H2O->SiMo (in the presence and
      absence of DCMU) and H2O->PPBQ, as well as the fluorescence induction curve of
      Tris-washed spinach PS II particles. Cu (II) inhibits both Hill reactions and, in
      the first case, the DCMU-insensitive H2O -> SiMo activity. In addition, the
      variable fluorescence is lowered by Cu (II). We have interpreted our results in
      terms of a donor side inhibition close to the reaction center. The same
      polarographic and fluorescence measurements carried out at different pHs indicate
      that Cu (II) could bind to amino acid residues that can be protonated and
      deprotonated. In order to reverse the Cu (II) inhibition by a posterior EDTA
      treatment, in experiments of preincubation of PS II particles with Cu (II) in
      light we have demonstrated that light is essential for the damage due to Cu (II)
      and that this furthermore is irreversible. 

PMID- 24301480
TI  - The Ile(L229) -> Met mutation impairs the quinone binding to the QB-pocket in
      reaction centers of Rhodobacter sphaeroides.
AB  - A spontaneous mutant (R/89) of photosynthetic purple bacterium Rhodobacter
      sphaeroides R-26 was selected for resistance to 200 MUM atrazin. It showed
      increased resistance to interquinone electron transfer inhibitors of o
      phenanthroline (resistance factor, RF=20) in UQo reconstituted isolated reaction
      centers and terbutryne in reaction centers (RF=55) and in chromatophores (RF=85).
      The amino acid sequence of the QB binding protein of the photosynthetic reaction
      center (the L subunit) was determined by sequencing the corresponding pufL gene
      and a single mutation was found (Ile(L229) -> Met). The changed amino acid of the
      mutant strain is in van der Waals contact with the secondary quinone QB. The
      binding and redox properties of QB in the mutant were characterized by kinetic
      (charge recombination) and multiple turnover (cytochrome oxidation and
      semiquinone oscillation) assays of the reaction center. The free energy for
      stabilization of QAQB (-) with respect to QA (-)QB was DeltaGAB=-60 meV and 0 meV
      in reaction centers and DeltaGAB=-85 meV and -46 meV in chromatophores of R-26
      and R/89 strains at pH 8, respectively. The dissociation constants of the quinone
      UQo and semiquinone UQo (-) in reaction centers from R-26 and R/89 showed
      significant and different pH dependence. The observed changes in binding and
      redox properties of quinones are interpreted in terms of differential effects
      (electrostatics and mesomerism) of mutation on the oxidized and reduced states of
      QB. 

PMID- 24301481
TI  - The role of chloroplast-encoded protein biosynthesis on the rate of D1 protein
      degradation in Dunaliella salina.
AB  - Mechanistic aspects of the Photosystem II (PS II) damage and repair cycle in
      Dunaliella salina were investigated. The work addressed the role of chloroplast
      encoded protein biosynthesis on the rate of the D1 protein (chloroplast psbA gene
      product) degradation, following photoinhibition of PS II under in vivo
      conditions. Cells were grown under different light-intensities and the rate of D1
      photodamage and degradation was measured via pulse-chase measurements with
      ((35)S)sulfate. It is shown that no detectable difference exists in the rate of
      D1 degradation in D. salina, measured in the presence or absence of lincomycin, a
      chloroplast protein biosynthesis inhibitor. The results suggest that de novo D1
      biosynthesis does not play a role in the regulation of D1 degradation. In low
      light (100 MUmol photons m(-2) s(-1)) grown cells, the rate of photodamage to D1
      did not exceed the rate of its degradation and replacement. In high-light (2200
      MUmol photons m(-1) s(-1)) grown cells, the rate of D1 photodamage was faster
      than the rate of its degradation, resulting in a significant accumulation of
      photoinactivated PS II centers in the chloroplast thylakoids (chronic
      photoinhibition). The latter was coincident with the appearance of a 160 kD
      complex that contained photodamaged D1. Electron micrographs of D. salina
      thylakoids revealed extensive grana stacks in the thylakoid membrane of low-light
      grown cells. Only rudimentary appressions consisting of simple membrane pairings
      were found in the high-light grown cells. The results are discussed in terms of
      the regulation of D1 degradation in chloroplasts under in vivo conditions. 

PMID- 24301482
TI  - Photosynthetic energy storage in aquatic leaves measured by photothermal
      deflection.
AB  - In a study of photosynthetic energy storage efficiency (ES), the adaxial surface
      of the leaves of Vallisneria americana exhibited the highest ES values (22%) of
      the four aquatic plants examined. V. americana leaves have a dispersed structure
      and it was possible to measure the energy storage properties of the epidermal
      cells independently of the rest of the leaf. The abaxial epidermis had a higher
      value of ES at zero light fluence than the adaxial epidermis but ES in the
      abaxial epidermis declined much more rapidly with light fluence. Thus the abaxial
      epidermis is more suited to lower light fluences than the adaxial epidermis. ES
      declined as the pH rose from 4.0 to 8.0 at a constant dissolved inorganic carbon
      concentration. This paralleled the change from carbon dioxide to bicarbonate and
      suggests that these leaves utilise CO2 more efficiently than bicarbonate. ES
      increased by about 50% at pH 8.0 as leaf sections further from the leaf tip were
      examined which demonstrates that the older epidermal cells are less well able to
      use bicarbonate. Exposure to 30 min of a saturating light fluence caused the
      epidermal chloroplasts to move from the periclinal walls to the anticlinal walls.
      This decreased the photothermal signal by increasing the thermal diffusion
      distance and lowering the light fluence due to greater chloroplast shading. The
      latter effect increased ES. It appears that chloroplast movement could assist the
      epidermis to survive harmful light fluences. 

PMID- 24301483
TI  - Regulation of violaxanthin de-epoxidase activity by pH and ascorbate
      concentration.
AB  - The activity of violaxanthin de-epoxidase has been studied both in isolated
      thylakoids and after partial purification, as a function of pH and ascorbate
      concentration. We demonstrate that violaxanthin de-epoxidase has a Km for
      ascorbate that is strongly dependent on pH, with values of 10, 2.5, 1.0 and 0.3
      mM at pH 6.0, 5.5, 5.0 and 4.5, respectively. These values can be expressed as a
      single Km+/-0.1+/-0.02 mM for the acid form of ascorbate. Release of the protein
      from the thylakoids by sonication was also found to be strongly pH dependent with
      a cooperativity of 4 with respect to protons and with an inflexion point at pH
      6.7. These results can explain some of the discrepancies reported in the
      literature and provide a more consistent view of zeaxanthin formation in vivo. 

PMID- 24301484
TI  - Erratum.

PMID- 24301485
TI  - Multilectin-assisted fractionation for improved single-dot tissue glycome
      profiling in clinical glycoproteomics.
AB  - To survey the glycome shift in cancer, single-dot tissue glycome profiling was
      improved by incorporating a lectin-assisted fractionation. The differential
      analysis of tissue specimens from colorectal cancer patients (n = 45) revealed
      that unfucosylated/alpha2,6-sialylated glycoproteins significantly increased in
      patients with poor prognoses. The detailed annotation will be an indispensable
      supplement for cancer-related glyco-biomarker discovery. 

PMID- 24301486
TI  - Association between delayed heart rate recovery and incident hypertension: a
      revisit of CARDIA.

PMID- 24301488
TI  - Comparative study of the morphology of stridulatory organs of the Iberian
      lycaenid butterfly pupae (Lepidoptera).
AB  - We compared the pupal stridulatory organs of 35 species and one subspecies of
      Iberian Lycaenidae using scanning electron microscopy. The studied species belong
      to the tribes Theclini, Eumaeini, Lycaenini, and Polyommatini. Nine species do
      not show stridulatory organs on the pupae but all other species possess them.
      Stridulatory organs are formed by a stridulatory plate (pars stridens) placed on
      the fifth abdominal segment and a file (plectron) in the sixth abdominal segment.
      The plate has tubercles in the Theclini and Lycaenini, tubercles, ridges, or
      undulations in the Eumaenini, and tubercles, teeth, or unspecialized structures
      in the Polyommatini. Morphological differences can be found in the files of the
      different tribes, regarding the number of teeth, their form and size. Cuticular
      formations of the organs were studied on a surface of 2,500 um(2) and the average
      of ridges, tubercles, and teeth was measured searching for relevant taxonomic
      information. Stridulatory organs were thought to be an adaptation to myrmecophily
      but we show that they are present both in myrmecophilous and nonmyrmecophilous
      species; therefore, we suggest that this trait probably did not evolve in
      relation with myrmecophily, but may be used to enhance relationships with ants.

PMID- 24301489
TI  - [New options in the treatment of atrial fibrillation].

PMID- 24301490
TI  - [Is thrombus aspiration during ST-segment elevation myocardial infarction
      beneficial? - routine thrombus aspiration is not indicated].

PMID- 24301491
TI  - [Evaluation of 12 pilot projects to improve outpatient palliative care].
AB  - BACKGROUND: With a priority programme the German Cancer Aid supported the
      development of quality-assured outpatient palliative care to cover the whole
      country. The 12 regional pilot projects funded with the aim to improve outpatient
      palliative care in different models and different frameworks were concurrently
      monitored and evaluated. METHODS: The supported projects, starting and ending
      individually, documented all patients who were cared for using HOPE (Hospice and
      palliative care evaluation) and MIDOS (Minimal documentation system for
      palliative patients). Total data were analyzed for 3239 patients decriptively. In
      addition to the quantitative data the experiences of the projects were recorded
      in a number of workshops (2008, 2009, 2010, and 2012). In particular, the
      experiences reported in the final meeting in July 2012 were considered for this
      article as well as the final reports for the German Cancer Aid. RESULTS: In the
      quantitative evaluation 85.6% of 3239 palliative care patients had a cancer
      diagnosis. In all model projects the goal of a network with close cooperation of
      primary providers, social support, and outpatient and inpatient specialist
      services has been achieved. For all projects, the initial financing of the German
      Cancer Aid was extremely important, because contracts with health insurance funds
      were negotiated slowly, and could then be built on the experiences with the
      projects. CONCLUSION: The participants of the project-completion meeting
      emphasized the need to carry out a market analysis before starting palliative
      care organizations considering the different regional structures and target
      groups of patients. Education, training and continuing education programs
      contribute significantly to the network. A reliably funded coordination
      center/case management across all institutions is extremely important.

PMID- 24301492
TI  - [Intussusception after Billroth II operation fifty years ago - an unusual cause
      for ileus].
AB  - HISTORY: A 77-year-old woman presented with occasional vomiting of hematin but no
      further complaints. 50 years ago a partial gastrectomy after Billroth II had been
      performed due to a gastric ulcer. INVESTIGATIONS: The physical examination
      revealed no pathologic findings. All laboratory values, including hemoglobin
      (HB), were in normal range. The gastroscopic examination showed traces of hematin
      in the stomach and in the efferent and afferent loop.  The Braun anastomosis
      could not be delineated. No other pathologic findings were noted. TREATMENT AND
      COURSE: At the request of the patient additional regular controls of hemoglobin
      were planned on an outpatient basis. In case of hemoglobin decrease, further
      treatment should be arranged. Two days after discharge the patient was presented
      with sudden massive abdominal pain and vomiting. Clinical examination confirmed
      the assumption of mechanical ileus. An emergency abdominal CT showed an
      intussusception of a small bowel loop into the Braun anastomosis as the ileus
      trigger. A laparotomy was carried out immediately after the CT. Because of severe
      ischemic damage of the intussuscepted loop, an "en bloc" resection of the loop
      including the Braun anastomosis including reanastomosis had to be carried out.
      CONCLUSION: Intussusception is primarily a childhood disease, occurring in adults
      only in about 5% of cases. Postoperative intussusception is a rare complication
      after gastric surgery.Especially because of its exceptionality the diagnosis of
      intussusception in adulthood can be difficult. Crucial herein is to have
      intussusception in mind in the differential diagnostic pathway of a post gastric
      surgery ileus.

PMID- 24301493
TI  - [43-year-old patient with syncope].

PMID- 24301494
TI  - [Autoimmune hepatitis].

PMID- 24301495
TI  - [Important aspects in pediatric care of children and adolescents with chronic
      disease using the example of bronchial asthma].
AB  - When treating children or adolescents with chronic disease one should take the
      specific age-related features of the course of disease, differential diagnosis,
      and the psychosocial environment, as well as the avoidance of complications and
      side effects of therapy into account. These may impair the patient's physical and
      psychosocial development and quality of life in the context of family, school and
      occupational life. Continued care of growing children from the start of the
      disease when they are infants to the point when they assume personal
      responsibility as adults is one of the major concerns of the pediatrician. This
      concept requires interdisciplinary cooperation and a large body of personnel
      which would include training programs, inclusion of family members and in some
      cases psychosomatic therapy. Given the increasing prevalence of chronic diseases
      in this age group and their sociopolitical significance it is important to
      activate preventive potentials in terms of content and structure - by quality
      assurance - especially to avoid long-term complications. Various care structures
      are used in Europe to achieve this goal. Asthma is the most common chronic
      disease in children and adolescents. It influences quality of life as well as the
      child's personal, educational and occupational development to a significant
      extent. The special aspects of the treatment of these patients will be addressed
      to illustrate the therapy of chronic disease. 

PMID- 24301496
TI  - [Snakes as pets - consequences of an exotic hobby].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a young man who presented at our
      emergency unit with pain and swelling of his left hand, after he had been bitten
      into his left middle finger by a sidewinder rattlesnake one hour ago.
      INVESTIGATIONS: Local findings were a swollen left middle finger, a red-livid
      discoloration along his nail rim with paleness of the surrounding skin. Vital
      signs were stable, ECG showed sinus rhythm, laboratory parameters were normal,
      without signs of liver or kidney damage and without coagulopathy. DIAGNOSIS,
      TREATMENT AND COURSE: Diagnosis was local tissue reaction due to a snake bite of
      a sidewinder rattlesnake without evidence of systemic toxic effect. Due to the
      absence of systemic toxic effects the patient received monitoring of his vital
      signs and we controlled local tissue reaction constantly and laboratory
      parameters every 6 hours, as recommended by the "Giftnotrufzentrale" (poison
      emergency advisory service). The patient left hospital on his own will against
      medical advice in the night after first laboratory control, which showed no signs
      of organ damage and we recommended reasessment the following morning. At that
      time the swelling had extended to the whole arm, furthermore large hematoma
      reaching up to the axilla had developed over night. Again we contacted the
      "Giftnotrufzentrale" and decided to begin the administration of an antivenom,
      after allergic testing. The administration was without complications, the
      swelling decreased constantly and since laboratory controll still showed no signs
      of systemic toxin effect, we could discharge the patient on day 3. Follow-up
      visit 6 months later showed complete and natural healing. CONCLUSION: Snake bites
      are altogether rare among our patients, nevertheless since possible toxin effects
      and its dynamics are unpredictable and can vary highly, they demand monitoring at
      close intervals of vitals signs, local swelling and laboratory parameters. As
      early as possible an advisory service, such as "Giftnotrufzentrale" should be
      contacted to acquire information on possible toxin effects and availability of
      antivenoms. Contact to other medical disciplines (e.g. dermatology, intensive
      care unit, surgery, neurology, dialysis...) should be sought, depending on the
      further course of toxin effects. Possible comorbidities as well as allergisation
      due to previous bites strongly influence the course of the disease and should be
      evaluated. We recommend to keep precise records on the ocurrence of systemic
      toxin effects, as well as on local findings (e.g. fotodocumentation, marking of
      erythema, measurement of swelling). Manipulation of the wound is usually
      ineffective and therefore not recommended, also in respect of self-endangerment.
      After stabilization of the patient a vaccination against tetanus, if necessary,
      should not be forgotten.

PMID- 24301497
TI  - [Early use of biological agents after first DMARD in rheumatoid arthritis - no].

PMID- 24301498
TI  - [Early use of biological agents after first DMARD in rheumatoid arthritis - no].

PMID- 24301499
TI  - Copies of Biomedical Chromatography. Editorial.

PMID- 24301500
TI  - Pollen stigma interactions in Brassica oleracea.
AB  - Recent studies on the mechanism of self-incompatibility in Brassica indicate the
      location, nature and mode of action of the molecules involved. Characteristics of
      the pollen surface and the stigma surface are described in detail, together with
      new information pertaining to the recognition molecules located therein. A
      sequence of events is outlined leading from pollination, through adhesion,
      hydration, germination, and tube growth to acceptance and ultimate compatibility.
      The characteristics of rejection of incompatible grains are described for each
      stage of the pollen-stigma interaction. It is proposed that recognition of
      proteins from the coating of self-pollen by the molecules in the pellicle results
      in the formation of a biologically-active complex which inhibits water supply to
      the incompatible grain, and that all other manifestations of incompatibility are
      a consequence of this initial response. 

PMID- 24301501
TI  - Genotypic effects of the maternal tissues of wheat on its grain weight.
AB  - Reciprocal crosses were made between semi dwarf spring wheat cultivars (Triticum
      aestivum L.) differing in grain weight. The weights of the F1 grains (on maternal
      spikes), from intact as well as from defoliated plants, and those of the F2
      grains (on f1 spikes), were examined. Grain weight was controlled primarily by
      the genotype of the maternal tissues (pericarp, testa or other floret or spikelet
      organs, including the vascular system), with complete dominance of heaviness. No
      indications suggesting maternal inheritance were obtained. The frequency
      distribution of the weights of the F2 grains indicated the presence of genotypic
      effects exerted by the endosperm or embryo. The embryo or endosperm factors for
      heaviness also seemed to be dominant. 

PMID- 24301502
TI  - The effect of distance between parents on the yield of sweet pepper x hot pepper
      hybrids, Capsicum annuum L. in a single harvest.
AB  - Crosses between a cytoplasmic male-sterile sweet pepper and 14 hot pepper lines
      were often heterotic for the traits yield/plant and red yield/plant. All the f1
      crosses were fertile and hot. All other F1 traits were intermediate to the
      parents' values. Phenotypic diversity among parents is not related to heterotic
      yield performance. Superior crosses must be found by trial and error. 

PMID- 24301503
TI  - Induction and analysis of gibberellin sensitive mutants in Arabidopsis thaliana
      (L.) heynh.
AB  - In Arabidopsis thaliana 37 independent irradiation or EMS induced mutants were
      isolated which have an absolute or almost absolute gibberellin (GA) requirement
      for germination and successive elongation growth. These are called 'non
      germinating GA-dwarfs', since without further addition of GA they develop into
      typical GA-dwarfs, being dark green, stunted and sterile. However, with repeated
      GA-treatment they develop into fertile plants with a completely wild type
      phenotype, or nearly so. In addition, 19 independently induced 'germinating GA
      dwarfs' were obtained, i.e. mutants which do germinate without GA but develop
      into typical GA-dwarfs. With repeated GA-treatment these too grow to become
      completely wild type phenotypes, or nearly so. 'Germinating dwarfs' have been
      found by previous authors in a number of other plant species. The 'non
      germinating dwarfs' form a new class of mutants. The system of non-germinating
      mutants offers a resolving power unique in higher plants, so that self-detecting
      rare events like induced revertants or intragenic recombinants can be efficiently
      screened for.The 56 GA-sensitive mutants represent mutations at 5 loci, located
      on three of five Arabidopsis chromosomes. At three of the five loci both mutant
      classes were represented in similar frequency ratio's, whilst at the other two
      loci only germinating dwarfs were found. 

PMID- 24301504
TI  - Genetic variation in tissue cultures of red clover.
AB  - Design II matings were made among randomly selected clones of 'Arlington' red
      clover (Trifolium pratense L.). Progeny were evaluated in vitro on two
      regeneration media for callus growth and differentiation. Additive genetic
      variance was a significant source of variability for nearly all traits evaluated,
      including somatic embryogenesis. In vitro traits, such as rapid callus growth,
      colony vascularization, root initiation, chlorophyll production and embryogenesis
      were highly heritable and should respond to breeding and selection. Dominance
      genetic variance was significant for only a few in vitro characters. Maternal and
      cytoplasmic factors were significant primarily in the early subcultures. Highly
      significant additive genetic correlation of performance on two regeneration media
      was found. A population selected on one of the regeneration media for such
      characteristics as improved plantlet regeneration, rapid callus growth, long term
      colony viability or the frequency of root initiation should show correlated
      improvement on the other medium. No significant differences for embryogenesis
      were attributable to differences in the regeneration media used. Furthermore, no
      interaction of additive genetic effects with regeneration media were observed.
      These data indicate that improvement in the frequency of plantlet regeneration
      from callus of red clover could effectively be achieved by breeding and selection
      for embryogenic types. 

PMID- 24301505
TI  - Interspecific crossability studies in poplars.
AB  - Pollen-stigma interactions were studied with scanning electron microscopy in
      intraspecific and intersectional crosses of Populus tremuloides (Sect. LEUCE); P.
      deltoides, P. nigra (Sect. AIGEIROS); and P. trichocarpa (Sect. TACAMAHACA).
      Intraspecific variation in hydration, size of hydrated pollen grains, and tube
      morphology is described. Exine sculpture in P. tremuloides was densely spinulate
      or scabrate, in P. trichocarpa densely reticulate, in the other species somewhat
      intermediate. In six of seven intersectional cross combinations pollen-tube
      behavior on the stigmatic surface at 5-22 hours after pollination was the same as
      in conspecific matings; in P. tremuloides x P. trichocarpa crosses, the
      percentage of twisted and bulging tubes was significantly higher. Irradiated
      mentor pollen did not affect pollentube behavior of adjacent incompatible pollen,
      but increased hybrid seedling production in interspecific crosses. By contrast,
      hexane treatment of pollen or stigma, and the spraying of catkins with
      gibberellic acid or naphtalene acetic acid were ineffective. The results are
      discussed in relation to several mechanisms presumed to be involved in
      restricting gene exchange among poplar species; and in relation to Hogenboom's
      (1973) incongruity concept. 

PMID- 24301506
TI  - Learning attentiveness.

PMID- 24301507
TI  - Religion and youth substance use.

PMID- 24301508
TI  - Crisis as opportunity for spiritual growth.
AB  - Life-history data from two hundred crisis families and two hundred non-crisis
      families are examined to specify the influence of crisis conditions on spiritual
      growth. Members of crisis families making spiritual values their basis for life
      orientation appear to live more productively and experience more life
      satisfaction than members of crisis families or non-crisis families making no
      conscious effort to examine values or life-orientation.These findings invite
      further substantiation of crisis as opportunity for spiritual growth. A clinical
      implication is that research on optimal functioning, recovery, and spiritual
      growth is perhaps more needed at present than continued research on pathology and
      dysfunction. 

PMID- 24301509
TI  - Music for the dance: Some meanings of solitude.
AB  - Solitude is explored as a helpful environment for spiritual and psychological
      health. A short description of the experience of solitude is followed by an
      examination of its place within the dynamic make-up of the person. Some
      consideration of how one "chooses" to enter into solitude is given. Some further
      questions for study are provided. 

PMID- 24301510
TI  - Psychoanalysis and theology: Two dialectics.
AB  - In the vocabulary of psychoanalysis, "health" means something roughly correlative
      to "salvation" in the vocabulary of theology. Both health and salvation assume
      some manner of change from a previous pathological or doomed state. Against this
      background this paper seeks to delineate two different possible models of change:
      One in which realityper se is changed as opposed to one in which theperception of
      reality is changed. In theology, the former can be represented by Paul and the
      latter by John. In psychoanalysis, Freud represented each point of view in his
      structural and topographical paradigms respectively. In contemporary
      psychoanalytical therapy, Otto Kernberg represents the former and Jacques Lacan
      the latter. 

PMID- 24301511
TI  - Chronic pain conceptualization and religious interpretation.
AB  - The pastoral counselor often interviews patients suffering from chronic pain.
      Many of them express religious notions about their suffering. This article
      examines some traditional concepts of pain and types of religious
      interpretations, and proposes appropiate roles for the pastoral counselor. 

PMID- 24301512
TI  - Myths, metaphors, and mentors.
AB  - This article begins with a discussion of myths as visions that transform life.
      The primary myth is that of death and rebirth. Metaphors are images which
      illumine our myths. Therapists are thus both scientists and poets. The process of
      being a mentor occurs in a variety of relationships. Our search is for an
      understanding of this process which then transcends the positions of master and
      disciple. Mentors need to have a sufficient degree of self-transcendence to
      enable the focus to be on the person's own unique vision. Mentors light sparks
      which ignite our myths and metaphors and thereby expand our understanding of
      ourselves. Mentors become catalysts for our growth and thereby facilitate the
      process of transformation. 

PMID- 24301513
TI  - Near-death experience as mystical experience.
AB  - Near-death experience exhibits many attributes of mystical awareness. Assessing
      the mystical quality of psychedelic experience, Walter Pahnke identified a nine
      category typology of mystical experience. It is used here to illustrate the
      mystical nature of near-death experience. The typology also describes the self
      transformation which follows the mystical state of consciousness. Self
      transformation results from near-death experience. Pahnke's mystical typology
      characterizes the near-death experience and allows for a definition of near-death
      experience as a mystical state. 

PMID- 24301514
TI  - "Aunt Grace can't have babies".
AB  - One of the most necessarily sensitive areas of pastoral care is dealing with
      perinatal death. This case study grows from a need for care providers to
      understand better the feelings of a mother in the loss of her baby. This
      particular exploration evolved from a taped interview with the writer's aunt (now
      in her seventies) and her dealings with the multiple losses she experienced over
      fifty years ago. Her conversation in the interview gives credibility to many
      coping skills that we endeavor to teach today and that she developed for herself
      out of a need to survive. 

PMID- 24301516
TI  - Satisfaction with the level and type of resource use of a health insurance scheme
      in Nigeria: health management organizations' perspectives.
AB  - Some developing countries have incorporated managed care elements into their
      national health insurance schemes. In practice, hybrid health management
      organizations (Hmos) are insurers who, bearing some resemblance to managed care
      in the USA, are vertically integrated in the scheme's revenue collection and pool
      and purchase healthcare services within a competitive framework. To date, few
      studies have focused on these organizations and their level of satisfaction with
      the scheme's optimal-resource-use (ORU) implementation. In Nigeria, the study
      site, Hmos were categorized on the basis of their satisfaction with ORU
      activities. One hundred forty-seven Hmo staff were randomly interviewed. The
      types of ORU domain categories were provider payment mechanism, administrative
      efficiency, benefit package inclusions and active monitoring mechanism. Bivariate
      analysis was used to determine differences among the Hmos' satisfaction with the
      various ORU domains. The Hmos' satisfaction with the health insurance scheme's
      ORU activities was 59.2% generally, and the associated factors were identified.
      According to the Hmos' perspectives related to the type of ORU, the fee-for
      service payment method and regular inspection performed weakly. Hmos' limited
      satisfaction with the scheme's ORU raises concerns regarding ineffectiveness that
      may hinder implementation. To offset high risks in the scheme, it appears
      necessary for the regulatory agency to adapt and reform strategies of provider
      payment and active monitoring mechanisms according to stakeholder needs. Our
      findings further reveal that having Hmos evaluate ORU is useful for providing
      evidence-based information for policy making and regulatory utilization related
      to implementation of the health insurance scheme.

PMID- 24301517
TI  - Particle size dependence on oxygen reduction reaction activity of
      electrodeposited TaO(x) catalysts in acidic media.
AB  - The size dependence of the oxygen reduction reaction activity was studied for
      TaO(x) nanoparticles electrodeposited on carbon black for application to polymer
      electrolyte fuel cells (PEFCs). Compared with a commercial Ta2O5 material, the
      ultrafine oxide nanoparticles exhibited a distinctively high onset potential
      different from that of the bulky oxide particles.

PMID- 24301518
TI  - Structural analysis and mapping of individual protein complexes by infrared
      nanospectroscopy.
AB  - Mid-infrared spectroscopy is a widely used tool for material identification and
      secondary structure analysis in chemistry, biology and biochemistry. However, the
      diffraction limit prevents nanoscale protein studies. Here we introduce mapping
      of protein structure with 30 nm lateral resolution and sensitivity to individual
      protein complexes by Fourier transform infrared nanospectroscopy (nano-FTIR). We
      present local broadband spectra of one virus, ferritin complexes, purple
      membranes and insulin aggregates, which can be interpreted in terms of their
      alpha-helical and/or beta-sheet structure. Applying nano-FTIR for studying
      insulin fibrils--a model system widely used in neurodegenerative disease research
      -we find clear evidence that 3-nm-thin amyloid-like fibrils contain a large
      amount of alpha-helical structure. This reveals the surprisingly high level of
      protein organization in the fibril's periphery, which might explain why fibrils
      associate. We envision a wide application potential of nano-FTIR, including
      cellular receptor in vitro mapping and analysis of proteins within quaternary
      structures.

PMID- 24301519
TI  - Can screening 4-5 year olds accurately identify children who will have teacher
      reported mental health problems when children are aged 6-7 years?
AB  - OBJECTIVE: To assess the screening accuracy of information obtained from parents
      of 4-5-year-old children for the purpose of identifying the children who have
      teacher-reported mental health problems when they are aged 6-7 years. METHOD: The
      study used data from the Longitudinal Study of Australian Children (LSAC)
      obtained when children were aged 4-5 years and 6-7 years. The level of children's
      mental health problems was assessed using the Strengths and Difficulties
      Questionnaire (SDQ) completed by parents when children were aged 4-5 years and by
      teachers when children were aged 6-7 years (n=2163). When children were aged 4-5
      years, parenting skills were assessed using three questionnaires developed for
      the parent-completed LSAC questionnaire and maternal mental health was assessed
      using the Kessler Psychological Distress Scale (K6). RESULTS: When the level of
      parent-reported childhood mental health problems at 4-5 years old was used to
      identify children with teacher-reported mental health problems (i.e. a score in
      the "abnormal" range of the teacher-reported SDQ Total Difficulties Scale) when
      the children were aged 6-7 years, sensitivity was 26.8%, positive predictive
      value was 22.8%, and specificity was 92.9%. The addition of further information
      about the characteristics of children and their parents made only a small
      improvement to screening accuracy. CONCLUSIONS: Targeted interventions for
      preschool children may have the potential to play an important role in reducing
      the prevalence of mental health problems during the early school years. However,
      current capacity to accurately identify preschoolers who will experience teacher
      reported mental health problems during the early school years is limited.

PMID- 24301520
TI  - The challenge of routine follow-up in e-mental health services.

PMID- 24301522
TI  - Switching suppression and enhancement of fluorescence and six-wave mixing by
      phase modulation.
AB  - The conversion between enhancement and suppression in six-wave mixing (SWM) and
      fluorescence signals by phase modulation has demonstrated for the first time. It
      is observed in our experiment the suppression of SWM and fluorescence is
      transformed into enhancement in company with the switch from electromagnetically
      induced transparency (EIT) to electromagnetically induced absorption (EIA) in the
      transmitted probe with the relative phase changed from 0 to pi/2. Our research
      could be potentially applied in optical communication and quantum information
      processing. 

PMID- 24301521
TI  - A FRET-based approach for identification of proteasome catalytic subunit
      composition.
AB  - Mammalian cells have two main types of proteasomes, the constitutive proteasome
      and the immunoproteasome, each containing a distinct set of three catalytic
      subunits. Recently, additional proteasome subtypes containing a non-standard
      mixture of catalytic subunits have gained increasing attention, especially due to
      their presence in cancer settings. However, practical methods for identifying
      proteasome subtypes have been lacking. Here, we report the development of the
      first fluorescence resonance energy transfer (FRET)-based strategy that can be
      utilized to identify different proteasome subtypes present within cells. We have
      developed FRET donor- and acceptor-probes that are based on previously reported
      peptide epoxyketones and selectively target individual proteasome catalytic
      subunits. Using the purified proteasome and cancer cell lysates, we demonstrate
      the feasibility of a FRET-based approach for determining the catalytic subunit
      composition of individual 20S proteasome subtypes. Ultimately, this approach may
      be utilized to study the functions of individual proteasome subtypes in cells. 

PMID- 24301525
TI  - Social and emotional adjustment of adolescents extremely talented in verbal or
      mathematical reasoning.
AB  - Perceptions of self-esteem, locus of control, popularity, depression (or
      unhappiness), and discipline problems as indices of social and emotional
      adjustment were investigated in highly verbally or mathematically talented
      adolescents. Compared to a group of students who are much less gifted, the highly
      gifted students perceive themselves as less popular, but no differences were
      found in self-esteem, depression, or the incidence of discipline problems. The
      gifted students reported greater internal locus of control. Comparisons between
      the highly mathematically talented students and the highly verbally talented
      students suggested that the students in the latter group perceive themselves as
      less popular. Within both the gifted and comparison groups, there were also
      slight indications that higher verbal ability may be related to some social and
      emotional problems. 

PMID- 24301523
TI  - Excess congenital non-synonymous variation in leukemia-associated genes in MLL-
      infant leukemia: a Children's Oncology Group report.
AB  - Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. Although
      most cases are accompanied by MLL rearrangements and harbor very few somatic
      mutations, less is known about the genetics of the cases without MLL
      translocations. We performed the largest exome-sequencing study to date on
      matched non-cancer DNA from pairs of mothers and IL patients to characterize
      congenital variation that may contribute to early leukemogenesis. Using the
      COSMIC database to define acute leukemia-associated candidate genes, we find a
      significant enrichment of rare, potentially functional congenital variation in IL
      patients compared with randomly selected genes within the same patients and
      unaffected pediatric controls. IL acute myeloid leukemia (AML) patients had more
      overall variation than IL acute lymphocytic leukemia (ALL) patients, but less of
      that variation was inherited from mothers. Of our candidate genes, we found that
      MLL3 was a compound heterozygote in every infant who developed AML and 50% of
      infants who developed ALL. These data suggest a model by which known genetic
      mechanisms for leukemogenesis could be disrupted without an abundance of somatic
      mutation or chromosomal rearrangements. This model would be consistent with
      existing models for the establishment of leukemia clones in utero and the high
      rate of IL concordance in monozygotic twins. 

PMID- 24301526
TI  - Parental discord vs family structure: effects of divorce on the self-esteem of
      daughters.
AB  - This study investigated the effects of family structure (parents together or not)
      and parental discord (ratings of the happiness of the marriage of biological
      parents) on the self-esteem of 199 female undergraduates. Family structure and
      happiness ratings were substantially related, with those separated rated as less
      happy. Self-esteem was significantly related to parental happiness, even with
      family structure controlled, but not to family structure with parental happiness
      controlled. With the sample divided into three groups (happy-together, unhappy
      together, and separated) ANOVA showed a significant effect for group, with the
      unhappy-together group showing significantly lower self-esteem than the happy
      together group, and the separated group intermediate. Parental discord thus
      appears to lower the selfesteem of daughters, whereas separation of parents does
      not. These findings support Heatherington's idea that children may be better off
      in a stable family where parents are divorced than in an intact family with much
      parental discord. 

PMID- 24301524
TI  - Proteasome inhibitors exert cytotoxicity and increase chemosensitivity via
      transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia.
AB  - The Notch signaling pathway has been recognized as a key factor for the
      pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), because of the high
      incidence of activating mutations of Notch1. Notch inhibition could serve as a
      new treatment strategy for T-ALL; however, the attempts to perturb Notch
      signaling pathways have been unsuccessful so far. In this study, we found that
      proteasome inhibitors exert cytotoxic effects on T-ALL cells with constitutive
      activation of Notch1 to a similar extent as myeloma cells. The proteasome
      inhibitor bortezomib repressed the transcription of Notch1 and downstream
      effectors including Hes1, GATA3, RUNX3 and nuclear factor-kappaB (NF-kappaB) (p65
      and p50), coincided with downregulation of the major transactivator Sp1 and its
      dissociation from Notch1 promoter. Overexpression of the Notch1 intracellular
      domain (NICD) significantly ameliorated bortezomib-induced cytotoxicity against T
      ALL cells. Drug combination studies revealed that bortezomib showed synergistic
      or additive effects with key drugs for the treatment of T-ALL such as
      dexamethasone (DEX), doxorubicin and cyclophosphamide, which were readily
      abolished by NICD overexpression. The synergy of bortezomib and DEX was confirmed
      in vivo using a murine xenograft model. Our findings provide a molecular basis
      and rationale for the inclusion of proteasome inhibitors in treatment strategies
      for T-ALL. 

PMID- 24301527
TI  - Psychological adjustment in a college-level program of marked academic
      acceleration.
AB  - The questionnaire responses of 24 markedly accelerated young students were
      compared with those of 24 regular-aged university students, 23 National Merit
      Scholars, and 27 students who had qualified for acceleration but instead elected
      to participate in high school. Measures included the Minnesota Multiphasic
      Personality Inventory, California Psychological Inventory, the Tennessee Self
      Concept Scale, and the Inventory of Parent and Peer Attachment. Accelerated
      students differed minimally from the college-aged groups, and not at all from
      high-ability age mates, on all of the measures, a finding contrary to the
      expectation that skipping high school is likely to be deleterious to one's
      adjustment. Both groups of normal-aged college students were more socially
      assertive. The accelerated students were less conforming and conventional than
      the others, but mean differences were small and not indicative of admustment
      difficulties. The study provides no basis for concern about the typical
      psychological and social adjustment of accelerated students. 

PMID- 24301528
TI  - Levels and psychosocial correlates of adolescent drug use.
AB  - Trends and patterns of adolescent drug use were examined through consideration of
      over 125 psychosocial correlates with drug use and nonuse. A sample of 480 urban
      high-school students was given personal interviews and a survey questionnaire
      that included several psychological scales and test batteries. A severity of drug
      use index was also employed in order to clarify the role of various causal
      factors at differential levels of drug-use severity. Study results seemed to
      confirm suggestions in the literature that drug use has become a normal,
      predictable form of behavior that accompanies adolescent development.
      Psychopathological factors were found to be important in cases of severe drug
      using behavior. The role of current, larger social structural factors in
      adolescent drug use is discussed, along with the programming and policy
      implications that stem from the multileveled structure of drug use. 

PMID- 24301529
TI  - School context, gender, and delinquency.
AB  - This study compares two high schools serving the same community and compares
      student bodies with similar background characteristics. The purpose is to examine
      how control/strain variables predict delinquency in two distinct school contexts.
      It was found that minor delinquency occurred more often in the environment
      dominated by competitive academic achievement, routine handling of discipline,
      and unpredictable supervision. Examination of the model paths suggest that this
      environment is also conservative and unlikely to offer legitimate opportunities
      to girls with gender-egalitarian orientation. The school context characterized by
      a broader definition of success, more specialized discipline, and predictable
      supervision promotes stronger bonds with its students and lower levels of
      delinquency for both genders. 

PMID- 24301530
TI  - Spectral and kinetic characterization of electron acceptor A1 in a Photosystem I
      core devoid of iron-sulfur centers F X, F B and F A.
AB  - The kinetic and spectroscopic properties of the secondary electron acceptor A1
      were determined by flash absorption spectroscopy at room and cryogenic
      temperatures in a Photosystem I (PS I) core devoid of the iron-sulfur clusters
      FX, FB and FA. It was shown earlier (Warren, P.V., Golbeck, J.H. and Warden, J.T.
      (1993) Biochemistry 32: 849-857) that the majority of the flash-induced
      absorbance increase at 820 nm, reflecting formation of P700(+), decays with a
      t1/2 of 10 MUs due to charge recombination between P700(+) and A1 (-). Following
      A1 (-) directly around 380 nm, where absorbance changes due to the formation of
      P700(+) are negligible, two major decay components were resolved in this study
      with t1/2 of ~ 10 MUs and 110 MUs at an amplitude ratio of ~ 2.5:1. The
      difference spectra between 340 and 490 nm of the two kinetic phases are highly
      similar, showing absorbance increases from 340 to 400 nm characteristic of the
      one-electron reduction of the phylloquinone A1. When measured at 10 K, the flash
      induced absorbance changes around 380 nm can be fitted with two decay phases of
      t1/2 ~ 15 MUs and 150 MUs at an amplitude ratio ~ 1:1. The difference spectra of
      both kinetic phases from 340 to 400 nm are similar to those determined at 298 K
      and are therefore attributed to charge recombination in the pair P700(+)A1 (-).
      These results indicate that the backreaction between P700(+) and A1 (-) is
      multiphasic when FX, FB and FA are removed, and only slightly temperature
      dependent in the range of 298 K to 10 K. 

PMID- 24301531
TI  - Dephosphorylation of the thylakoid membrane light-harvesting complex-II by a
      stromal protein phosphatase.
AB  - Light-harvesting complex-II (LHC-II) phosphatase activity has generally been
      examined in the intact thylakoid membrane. A recent report of peptide-phosphatase
      activity associated with the chloroplast stromal fraction (Hammer, M.F. et al.
      (1995) Photosynth Res 44: 107-115) has led to the question of whether this
      activity is capable of dephosphorylating membrane-bound LHC-II. To this end, heat
      treated thylakoid membranes were examined as a potential LHC-II phosphatase
      substrate. Following incubation of the thylakoid membrane at 60 degrees C for 15
      min, the endogenous protein phosphatase and kinase activities were almost
      eliminated. Heat-inactivated phosphomembranes exhibited minimal dephosphorylation
      of the light harvesting complex-II. Peptide-phosphatase activities isolated from
      the thylakoid and stromal fraction were able to dephosphorylate LHC-II in heat
      inactivated phosphomembranes. The stromal phosphatase showed highest activity
      against LHC-II at pH 9. Dephosphorylation of the LHC-II by the stromal enzyme was
      not inhibited by molybdate, vanadate or tungstate ions, but was partially
      inhibited by EDTA and a synthetic phosphopeptide mimicking the LHC-II
      phosphorylation site. Thus, the previously identified stromal phosphatase does
      appear capable of dephosphorylating authentic LHC-II in vivo. 

PMID- 24301532
TI  - Reversible photochemistry in a chlorophyll model system.
AB  - A reversible, endothermic photochemical redox reaction, sensitized by chlorophyll
      a and related compounds, has been demonstrated in a heterogeneous particulate
      system. The oxidant, 5,5'-dithiobis(2-nitrobenzoate) (DTNB), is photoreduced to
      the thiolate which remains primarily in an aqueous phase. Reductants are
      trisubstituted hydrazines, capable of oxidation to tetrazanes in the hydrocarbon
      particle phase. In the course of three days in the dark, thiolate and tetrazane
      react to regenerate DTNB in yields approaching 100%. A novelty of the present
      system is that photoreaction often takes place in discrete rate regimes, which
      are related to the presence of spectrally identifiable associations of
      chlorophyll pigments, Mg-containing and free bases. Among the associations that
      promote photochemical activity are those of chlorophyll and pheophytin with
      themselves and with each other. Perhaps more active are associations of a Mg
      rhodochlorin allomerization product of chlorophyll with its free base.
      Contributing to the associations is the stabilizing presence of amphiphiles that
      both ligate the Mg of chlorophyll strongly and hydrogen-bond to carbonyls: 2
      tridecylimidazole, 2-tridecylimidazoline, and (2-aminoethyl)myristamide. Results
      of this work demonstrate the possibility of generating reaction center models in
      an artificial heterogeneous system, and of conducting reversible photochemical
      reactions with them. 

PMID- 24301533
TI  - Intracellular localization of CA1P and CA1P phosphatase activity in leaves of
      Phaseolus vulgaris L.
AB  - CA1P and CA1P phosphatase occur in the chloroplasts of leaf mesophyll cells of
      many species. However, whether either may occur exclusively in the chloroplast
      has not yet been established. To examine their intracellular distribution,
      mature, dark-or light-treated leaves of Phaseolus vulgaris were frozen,
      lyophilized and then centrifuged in density gradients of heptane and
      tetrachloroethylene. After gradient fractionation, both CA1P and CA1P phosphatase
      activity co-segregated with chloroplast material. Distribution analyses using sub
      cellular compartment markers indicated that both CA1P and CA1P phosphatase do
      occur exclusively in leaf chloroplasts. 

PMID- 24301534
TI  - Imaging of chlorophyll-a-fluorescence in leaves: Topography of photosynthetic
      oscillations in leaves of Glechoma hederacea.
AB  - Images of chlorophyll-a-fluorescence oscillations were recorded using a camera
      based fluorescence imaging system. Oscillations with frequencies around 1 per min
      were initiated by a transient decrease in light intensity during assimilation at
      an elevated CO2-concentration. The oscillation was inhomogenously distributed
      over the leaf. In cells adjacent to minor veins, frequency and damping rate was
      high, if there was any oscillation. In contrast, the amplitude was highest in
      cells most distant from phloem elements (maximal distance about 300 MUm). The
      appearance of minor veins in oscillation images is explained by a gradient in the
      metabolic control in the mesophyll between minor veins and by transport of sugar
      from distant cells to phloem elements. The potential of fluorescence imaging to
      visualize 'microscopic' source-sink interactions and metabolic domains in the
      mesophyll is discussed. 

PMID- 24301535
TI  - In search of a reversible stage of photoinhibition in a higher plant: No changes
      in the amount of functional Photosystem II accompany relaxation of variable
      fluorescence after exposure of lincomycin-treated Cucurbita pepo leaves to high
      light.
AB  - Pumpkin (Cucurbita pepo L.) leaves in which chloroplast protein synthesis was
      inhibited with lincomycin were exposed to strong photoinhibitory light, and
      changes in FO, FM, FV/FM and in the amount of functional Photosystem II (O2
      evolution induced by saturating single-turnover flashes) were monitored during
      the high-light exposure and subsequent dark or low-light incubation. In the
      course of the photoinhibitory illumination, FM, FV/FM and the amount of
      functional PS II declined continuously whereas FO dropped rapidly to some extent
      and then slowly increased. If the experiments were done at room temperature,
      termination of the photoinhibitory illumination resulted in partial relaxation of
      the FV/FM ratio and in an increase in FO and FM. The relaxation was completed in
      10-15 min after short-term (15 min) photoinhibitory treatment but continued 30-40
      min if the exposure to high light was longer than 1 h. No changes in the amount
      of functional PS II accompanied the relaxation of FV/FM in darkness or in low
      light, in the presence of lincomycin. Transferring the leaves to low temperature
      (+4 degrees C) after the room-temperature illumination (2 h) completely inhibited
      the relaxation of FV/FM. Low temperature did not suppress the relaxation if the
      photoinhibitory illumination had also been done at low temperature. The results
      indicate that illumination of lincomycin-poisoned pumpkin leaves at room
      temperature does not lead to accumulation of a reversibly photoinactivated
      intermediate. 

PMID- 24301536
TI  - An enhanced developmental staging table for the painted turtle, Chrysemys picta
      (Testudines: Emydidae).
AB  - Normal developmental staging tables often undergo expansion and enhancement in
      response to advancing research paradigms and technologies. The Painted Turtle,
      Chrysemys picta, has long been a preferred reference taxon for comparative
      embryology and recently became the first turtle species to feature a sequenced
      genome. However, modern descriptive studies on embryogenesis are lacking and an
      earlier developmental staging table has been ignored. To address these problems,
      we re-evaluated descriptions of developmental stages by studying embryos under
      standardized laboratory conditions. We created an enhanced normal developmental
      staging table that clarifies and validates previous descriptions of developmental
      processes in this species. Moreover, we emphasized description of turtle-specific
      developmental characters such as the carapacial ridge. We demonstrated that
      embryo growth rate, length of incubation period, and timing to developmental
      stages are predictable under controlled environmental conditions. The appearance
      of characters associated with eye, limb, and shell anatomy was congruent with
      observations made in other turtle species. To reduce experimental bias, we
      recommend the use of our enhanced staging table when describing embryogenesis in
      the Painted Turtle.

PMID- 24301538
TI  - Metallamacrocycle-modified gold nanoparticles: a new pathway for surface
      functionalization.
AB  - We report herein the designed synthesis of four silver(I)- or gold(I)-bridged
      flexible metalla-macrocycles (MMCs) and their distinct performance in the surface
      modification of gold nanoparticles (AuNPs). The resulting gold(I)-MMCs-modified
      AuNPs were found to be resistant to pH variation and capable of binding with
      metal ions.

PMID- 24301539
TI  - Excited-state dynamics of thiophene substituted betaine pyridinium compounds.
AB  - This work deals with the photophysics of novel pyridinium betaine based on 2
      pyridin-1-yl-1H-benzimidazole (SBPa) substituted symmetrically by mono- (Th2SBPa)
      and bi-thiophene fragments (Th4SBPa). The study is based on a combination of
      steady-state, femtosecond transient absorption spectroscopic measurements
      supported by PCM-(TD)DFT calculations. It is found that the two step ICT process
      (S0 -> S2 excitation followed by S2(CT) -> S1(CT) internal conversion) occurring
      for the parent molecule remains unaffected for Th2SBPa while the situation is
      less clear for Th4SBPa. Actually, for both molecules, a new decay route involving
      the pi-electron system localized in thiophenic groups is responsible for the
      production of triplet states. Involvement of this new route in the parallel
      production of S1(CT) is strongly suspected. 

PMID- 24301537
TI  - Early effects of parathyroid hormone on bisphosphonate/steroid-associated
      compromised osseous wound healing.
AB  - SUMMARY: Administration of intermittent parathyroid hormone (PTH) promoted
      healing of tibial osseous defects and tooth extraction wounds and prevented the
      development of necrotic lesions in rats on a combined bisphosphonate and steroid
      regimen. INTRODUCTION: Osteonecrosis of the jaw (ONJ) has emerged in association
      with antiresorptive therapies. The pathophysiology of ONJ is unknown and no
      established cure currently exists. Our objective was to determine the effect of
      intermittent PTH administration on early osseous healing in the jaw and long
      bones of rats receiving bisphosphonate and steroid treatment. METHODS:
      Ovariectomized rats received the combination therapy of alendronate and
      dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and
      tibia. PTH was administered intermittently and healing at 2 weeks post-op was
      compared between the jaw and tibia by microcomputed tomography and
      histomorphometric analyses. RESULTS: ALN/DEX treatment was associated with
      necrotic open wounds in the jaw but had no negative effects on healing and
      promoted bone fill in tibial defects. PTH therapy prevented the development of
      necrotic lesions in the jaw and promoted healing of the tibial defects. PTH
      therapy was associated with the promotion of osteocyte survival in osseous wounds
      both in the jaw and tibia. CONCLUSIONS: Wound healing was impaired in the jaw in
      rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued
      necrotic lesions. These findings suggest that PTH therapy could be utilized to
      prevent ONJ from occurring in patients on combination antiresorptive and steroid
      therapy.

PMID- 24301540
TI  - Inhibition of feeding by a generalist insect due to increased volatile leaf
      terpenes under nitrate-limiting conditions.
AB  - Nitrogen-limited plants ofHeterotheca subaxillaris accumulate greater quantities
      of leaf volatile terpenes than do nitrogen-rich plants. A series of feeding
      trials were performed to determine if such nitrate-limited plants are better
      defended against generalist-feeding insect herbivores. Soybean looper
      (Pseudoplusia includens) larvae were fed leaves fromH. subaxillaris rosettes
      grown under high and low nitrate supply regimes. Larval consumption, growth, and
      survival declined as the leaf volatile terpene content increased. Larval
      consumption and growth were enhanced by higher plant nitrate supply and with
      increasing leafage. The results suggest that the higher quantity of volatile
      terpenes in the leaves of nitrate-limited plants may better defend these leaves
      against generalist-feeding insects. 

PMID- 24301541
TI  - Significance of saguaro cactus alkaloids in ecology ofDrosophila mettleri, a soil
      breeding, cactophilic drosophilid.
AB  - Drosophila mettleri is a soil-breeding, cactophilic drosophilid which lives in
      the Sonoran Desert. Several chemical constituents of cacti in this region have
      been identified as having major roles in insect-host plant relationships
      involvingDrosophila. For example, isoquinoline alkaloids, which are present in
      senita cactus, have been shown to be toxic to seven of the nine species tested.
      The two tolerant species areD. pachea, the normal resident, andD. mettleri.
      Necroses of senita cacti are often used as feeding substrates byD. mettleri
      adults, but this species has never been reared from senita rots. Soil, which have
      been soaked by juice from saguaro and cardon rots, are the typical breeding
      substrates of this species. The tissues of both of these cacti also contain
      alkaloids, chemically related to those in senita, but at much lower
      concentrations. Alkaloid concentration in saguaro-soaked soil was found to be 1.4
      27 times the average concentration in fresh tissue. Alkaloids were extracted from
      saguaro tissue and used in tests of larva-to-adult viability, developmental rate,
      and adult longevity. Elevated concentrations of saguaro alkaloids had no
      significant effect on the longevity ofD. mettleri, but significantly reduced the
      longevity ofD. nigrospiracula andD. mojavensis, two nonsoil breeding cactophilic
      species. Viability and developmental rates of all three species were affected,
      but the effect onD. nigrospiracula was comparatively greater. It is argued that
      the adaptations that allowD. mettleri to utilize the saguaro soil niche also
      convey tolerance to alkaloids present in senita tissue. The ability to utilize
      senita necroses as feeding substrates represents an ecological advantage to D.
      mettleri, in that the density of potential feeding sites is increased as compared
      to species which are more specific in their host-plant relationships. 

PMID- 24301542
TI  - Perspectives on allelopathy in mexican traditional agroecosystems: A case study
      in tlaxcala.
AB  - Agroecosystems in Tlaxcala, Mexico, are surrounded by trees and water channels
      and have a great variety of cultivated and noncultivated plants. The main results
      of a study carried out on a traditional agroecosystem in Santa Ines, Tlaxcala are
      presented. Some ecological aspects of polycultures, plant covers (dry leaves
      ofAlnus firmifolia, Berula erecta, andJuncus sp.), and the allelopathic potential
      of crops and noncultivated plants (fresh and dry material) were analyzed. The
      main plants (trees, shrubs, and herbs) present in the agroecosystem were
      identified. The total number of weeds in plots where plant covers were added was
      reduced. The number of nodules ofRhizobium phaseoli and the production of bean
      and squash increased with plant covers. Corn, beans, and squash showed a clear
      allelopathic effect, as well asChenopodium murale, Tradescantia crassifolia,
      Melilotus indicus, andAmaranthus hybridus, among other weeds. The contribution of
      allelopathy in studies of traditional agroecosystems is of great importance for
      the management of species in space and time. Allelopathy can be the basis of
      biological control of pests and weeds and of the discovery of new useful
      substances. 

PMID- 24301543
TI  - Analysis of peach bark volatiles and their electroantennogram activity with
      lesser peachtree borer,Synanthedon pictipes (Grote and Robinson).
AB  - Bark volatiles from two peach cultivars (Bisco and Redskin) were obtained by
      vacuum steam distillation and fractionated by preparative gas chromatography. The
      fractions were then assayed with the electroantenno- gram (EAG) method on
      antennae of female lesser peachtree borer [Synanthedon pictipes (Grote and
      Robinson)]. With both cultivars, two fractions elicited the largest responses.
      Analysis of this material by GC-MS revealed a complex mixture made up of aromatic
      alcohols, esters, ketones, and acids, as well as phenols, aliphatic aldehydes,
      and aliphatic acids. EAG responses to pure samples of all identified components
      were recorded, and many of these compounds were found to be quite active. Among
      the most stimulatory were guaiacol, methyl benzoate, and l-phenyl-1,2
      propanedione. Also tested were six-carbon aliphatic aldehydes and alcohols which
      are components of the foliar tissue of most plants. Of these, 1-hexanol showed
      moderate activity, while the aldehydes and unsaturated alcohols were only weakly
      active. 

PMID- 24301544
TI  - Digestion and absorption ofEucalyptus essential oils in greater glider
      (Petauroide svolans) and brushtail possum (Trichosurus vulpecula).
AB  - Measurements were made of the quantity and composition of the steam-volatile
      essential oils in gastrointestinal tract contents of greater gliders
      fedEucalyptus radiata foliage and brushtail possums fedE. melliodora foliage. In
      both species, there was less oil in the stomach contents than in an equivalent
      mass of foliage. Only minor losses of leaf oils occurred during mastication by
      greater gliders, and absorption from the stomach appeared to be the major reason
      for the difference in the oil content of ingested leaves and of stomach contents.
      The apparent digestibility of oils over the whole gut was 96-97 %, although oils
      from the cecum and feces of both species contained compounds not present in the
      original leaf oils. Absorption of oils before they reach the hindgut should
      reduce the severity of antimicrobial effects but may involve a metabolic cost to
      the animal in detoxification and excretion. 

PMID- 24301545
TI  - In search of values.

PMID- 24301546
TI  - An existential interpretation of success neurosis.
AB  - The fear of success is typically interpreted as a neurosis in which the fear of
      change plays a central role. In spite of agreeing with the existence of this
      syndrome in clinical practice. this author holds that a similar ambivalence about
      change lurks within ourselves as well. We are especially like patients in that,
      in spite of their often unique conflicts, they also run away, like us, from true
      success. In defining the latter, the author interprets it as synonymous with
      living an ethical life filled with reverence and respect for all. 

PMID- 24301547
TI  - Theological foundations for spiritual care.
AB  - Five theological tenets are described which may undergird the integration of
      religious awareness and spiritual care into nursing curricula. The five all
      emphasize addressing the articulated needs of the patient within the context of
      the nursing process. These tenets, while Wesleyan in emphasis, suggest ways in
      which any nurse may engage in the common ministry of all Christians without
      usurping the role of clergy or chaplains. 

PMID- 24301548
TI  - Loving: A developmental challenge of middle age.
AB  - The capacity to love fully is one of the central developmental challenges of
      middle age. Loving is predicated upon the dynamic synthesis of trusting,
      autonomous, and creative relationships during childhood and adolescence. With the
      emergence of a productive orientation during middle age, it becomes increasingly
      clear that it is important to work for that which we love. It is impossible to
      encapsulate the essence of loving, but it can be partially delineated in terms of
      care, responsibility, respect, and knowledge. As a loving relationship develops,
      sexuality may emerge as another phase of mutuality. However, many loving
      relationships have no sexual overtones. In summary, loving is an end experience,
      for it engenders the joy that comes from being fully alive. 

PMID- 24301549
TI  - The cultural psychology of Kohut's self psychology.
AB  - Contrary to criticism, Heinz Kohut's self psychology does not support an
      absorption into self nor a morally neutral response to society. Kohut's
      psychology of the self and narcissism aims toward an analysis of contemporary
      Western culture that will restore it. In the process of assisting individuals and
      culture to recover from the vicissitudes of narcissism, Kohut has introduced a
      new type of cultural psychology, a "culture of empathy". 

PMID- 24301550
TI  - The funeral meal: A significant funerary ritual.
AB  - Historically, a meal in association with funerary ritual has been a reality in
      many cultural and religious settings. Our society has experienced a gradual
      demise of formal funerary ritual, with an accompanying psychological and social
      impoverishment. Both the immediate bereaved and the larger social community can
      benefit from a funeral meal which functions as a group experience that focuses on
      the needs of the living. It can be a shared experience in a familiar structured
      setting which enables the living to do significant grief work. Practical
      implications and potential problems will need to be, taken into consideration. 

PMID- 24301551
TI  - The therapeutic value in the autopsy request.
AB  - Recently the number of autopsies performed in the United States has declined.
      Although the benefits of the autopsy for physicians are many, we maintain, based
      on our own experiences, that it helps them accept the reality of loss of a loved
      one and enables them to begin the process of "letting go". Realization of the
      therapeutic value of the autopsy request should enable those who work with the
      recently bereaved, such as physicians and clergy, to fulfill more effective
      roles. 

PMID- 24301552
TI  - Role of surgical resection in complete responders on FDG-PET after
      chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: To determine the role of surgery in complete
      responders on FDG-PET after CRT and the prognostic significance of metabolic
      response in locally advanced esophageal squamous cell carcinoma. METHODS: We
      retrospectively reviewed 154 patients with locally advanced esophageal cancer
      with increased uptake on FDG-PET. Eighty-one patients received definitive CRT and
      73 received trimodality therapy. We defined metabolic complete remission (PET-CR)
      when FDG uptake of the primary tumor and lymph nodes were decreased and was
      indistinguishable from surrounding normal tissue. Oncologic outcomes were
      compared between trimodality group, definitive CRT group, and PET-CR subgroup of
      definitive CRT. RESULTS: Thirty-one (38.3%) of the definitive CRT patients and 39
      (53.4%) of the trimodality therapy patients achieved PET-CR after CRT. The 2-year
      OS of the trimodality group was higher than that of the definitive CRT group, but
      equivalent to that of the PET-CR subgroup of definitive CRT. The 2-year LRFS and
      DFS of the trimodality group were higher than that of the PET-CR subgroup or the
      entire of definitive CRT group. CONCLUSION: The addition of surgery showed higher
      DFS and LRFS rates than those of the PET-CR subgroup of definitive CRT. Despite
      achieving PET-CR, surgery still seems to improve local tumor control.

PMID- 24301553
TI  - "Still crazy after all these years"--tuberculosis as an old disease with diverse
      facets in a thirty-five-year-old male patient.
AB  - We report about a thirty-five-year-old male patient with miliary TB as first
      manifestation of HIV-infection. 

PMID- 24301554
TI  - [Effectiveness and practicality of an internet-based asthma refresher course for
      children and adolescents].
AB  - BACKGROUND AND METHODS: The effectiveness and practicality of the "Luftikids"
      (www.luftikids.de) structured, internet-based asthma refresher course was
      evaluated in a pilot study with 53 patients (ages 8 - 14 years). All patients had
      previously participated in either an inpatient or outpatient asthma education
      program. This prospective study examined the effect of a 4-week refresher course
      on parameters such as asthma symptoms (coughing, dyspnea), the number of
      unscheduled doctor's visits, use of on-demand medications, number of days absent
      from school, and asthma monitoring using the Asthma Control Questionnaire (ACQ)
      and lung function tests. The duration of program use and the number of logins was
      used to investigate acceptance of the game format. Data were collected at the
      beginning of the study and at 4 - 6 months after the end of the online refresher
      course. RESULTS: Significant changes were shown with regard to the decrease in
      intensity of asthma symptoms such as coughing (p = 0.001) and dyspnea (p =
      0.007), reduction in the number of unscheduled doctor's visits (p = 0.005), the
      use of on-demand medications (4.0 +/- 6.5 vs. 1.5 +/- 4.9, p = < 0.002), and the
      number of days absent from school (1.2 +/- 2.0 vs. 0.4 +/- 1.2, p = 0.003). No
      changes in lung function parameters were observed. The "Luftikids" program was
      used for an average of 302.5 +/- 210.9 minutes, and the number of logins was 14
      +/- 9. From their self-evaluations, the children and adolescents derived "much"
      to "very much" benefit. Only 7.5% reported no effect. CONCLUSIONS: Participation
      in the "Luftikids" internet-based asthma refresher course resulted in fewer
      asthma symptoms, a decrease in unscheduled doctor's visits, reduction in the use
      of on-demand medications, decrease in the number of days absent from school, and
      improved asthma knowledge. No effect in lung function could be demonstrated. The
      results support the effectiveness and good acceptance of an outpatient, internet
      based asthma refresher course. Young asthma patients in particular can succeed
      with and be motivated by this form of refresher course.

PMID- 24301555
TI  - Impact of national guidelines on brachytherapy monotherapy practice patterns for
      prostate cancer.
AB  - BACKGROUND: In 1999 and 2000, 2 national guidelines recommended brachytherapy
      monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high
      risk prostate cancer. This study examined rates of BT use before and after
      publication of these guidelines, as compared with 4 other treatment options.
      METHODS: From 1990 to 2011, 8128 men with localized prostate cancer (<= T3cN0M0)
      were treated definitively within the Cancer of the Prostate Strategic Urologic
      Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external
      beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or
      radical prostatectomy. Men were categorized into low-, intermediate-, and high
      risk groups based on the guidelines' risk-group definitions. Within each risk
      group, logistic regression was used to estimate odds ratios (OR) comparing BT
      with other treatment options between the 1990-1998 and 1999-2011 periods,
      adjusting for age, disease characteristics, and clinic type. RESULTS: In total,
      1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high
      risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus
      16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after
      adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low-
      (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk
      groups (OR = 2.11; P < .001). CONCLUSIONS: National guidelines did not appear to
      influence practice patterns, as BT monotherapy use increased relative to other
      treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups
      including men with high-risk prostate cancer.

PMID- 24301556
TI  - Half of drug trials with results on ClinicalTrials.gov are not published in
      journals.

PMID- 24301557
TI  - The relevance and applicability of oocyst prevalence as a read-out for mosquito
      feeding assays.
AB  - Mosquito feeding assays are important in evaluations of malaria transmission
      reducing interventions. The proportion of mosquitoes with midgut oocysts is
      commonly used as an outcome measure, but in natural low intensity infections the
      effect of oocyst non-rupture on mosquito infectivity is unclear. By identifying
      ruptured as well as intact oocysts, we show that in low intensity P. falciparum
      infections i) 66.7-96.7% of infected mosquitoes experienced oocyst rupture
      between 11-21 days post-infection, ii) oocyst rupture led invariably to
      sporozoite release, iii) oocyst rupture led to salivary gland infections in 97.8%
      of mosquitoes, and iv) 1250 (IQR 313-2400) salivary gland sporozoites were found
      per ruptured oocyst. These data show that infectivity can be predicted with
      reasonable certainty from oocyst prevalence in low intensity infections. High
      throughput methods for detecting infection in whole mosquitoes showed that 18s
      PCR but not circumsporozoite ELISA gave a reliable approximation of mosquito
      infection rates on day 7 post-infection. 

PMID- 24301558
TI  - Uptake epithelia behave in a cell-centric and not systems homeostatic manner in
      response to zinc depletion and supplementation.
AB  - Much remains to be understood about systemic regulation of zinc uptake in
      vertebrates, and adequate zinc status is far from always achieved in animals or
      human. In addition to absorbing zinc from the diet, fish are able to take up zinc
      directly from the water with the gills. This provides an elegant system to study
      zinc uptake, how it relates to zinc status, and the expression of genes for
      proteins involved in zinc acquisition. A 21-day experiment was conducted in which
      zebrafish were acclimated to deficient, control or excess zinc concentrations in
      the water and feed. Deficient provision of zinc reduced whole body zinc,
      potassium, sodium and calcium levels whilst zinc concentrations in the uptake
      epithelia (gills and gut) remained unchanged. Excess levels of zinc caused
      accumulation of zinc in the gills, intestine and carcass, but impaired whole body
      iron, sodium and calcium concentrations. Fish subjected to zinc deficiency had,
      surprisingly, a reduced zinc influx across the gill epithelium, even when tested
      at a high concentration of zinc in the water. Zinc influx in the excess group was
      indistinct from the control. Expression of genes for metallothionein-2 (Mt2) and
      zinc transporters-1, -2, and -8 (Znt1, Znt2, Znt8) in uptake epithelia showed in
      general a direct relationship with zinc supply, while mRNA for Zip4 was inversely
      related to zinc supply. Transcripts for the epithelial calcium channel
      (Ecac/Trpv6) showed time-dependent increased expression in the gills of the
      deficiency group, and a transient decrease of expression during zinc excess.
      Transcriptome profiling by microarrays showed that in both gills and intestine,
      the most markedly affected biological functions were those related to cell
      growth, proliferation and cancer, closely followed by processes of gene
      transcription and protein synthesis in general. Whilst changes in zinc supply had
      profound effects in the intestine on genes associated with uptake and metabolism
      of macronutrients, many of the unique categories of genes preferentially
      regulated in the gill could be mapped onto signalling pathways. This included
      pathways for PPAR/RXR, LXR/RXR, ATM, chemokine, and BMP signalling. Overall, the
      responses of epithelial tissue to zinc deficiency and excess are best explained
      by local epithelial homeostasis with no evidence of systemic control. 

PMID- 24301559
TI  - Preface.

PMID- 24301560
TI  - The life of Daniel I. Arnon.

PMID- 24301561
TI  - Daniel I. Arnon: Portrayal of a research career.

PMID- 24301562
TI  - Mineral nutrition of plants.

PMID- 24301563
TI  - Photosynthesis by isolated chloroplasts: The early work in Berkeley.

PMID- 24301565
TI  - Photosynthesis, inorganic plant nutrition, solutions, and problems.
AB  - A brief account is given of the research that D.I. Arnon did before he ventured
      into the field of photosynthesis, viz. his work on inorganic plant nutrition in
      the laboratory of D.R. Hoagland. The connection between the two areas is
      indicated. In his work on plant nutrition Dr Arnon emphasized the role of
      specific nutrients and, with P.R. Stout, formulated a definition of essentiality
      that is used to this day. It is now necessary, however, to take into account
      elements not meeting their criteria of essentiality, as shown by a consideration
      of the element silicon. 

PMID- 24301564
TI  - Perspective on Daniel I. Arnon's contributions to research, 1960-1994.

PMID- 24301566
TI  - Polyphenol oxidase and photosynthesis research.
AB  - Very briefly, the present state of knowledge on the latent, lumen oriented
      polyphenol oxidase (PPO) of the chloroplast is reviewed. The location of PPO in
      the thylakoid membrane was described by D. Arnon 46 years ago. The N-terminus
      sequence of the spinach enzyme is reported. A historical sketch is given of the
      discovery of photophosphorylation and Arnon's visit to the admired O. Warburg. 

PMID- 24301567
TI  - One thing leading to another.

PMID- 24301568
TI  - Divergent pathways of photosynthetic electron transfer: The autonomous oxygenic
      and anoxygenic photosystems.
AB  - The aim of this article is to assemble and integrate, from a personal perspective
      of a research participant, seldom examined evidence that is incompatible with
      some basic tenets of photosynthetic electron transport, the cornerstone of which
      is the Z scheme. The nonconforming evidence pertaining to the mode of ferredoxin
      reduction and the role of the copper redox protein, plastocyanin, indicates that
      contrary to the Z scheme ferredoxin is reduced in two experimentally
      distinguishable ways: oxygenically by PS II (renamed the oxygenic photosystem),
      without the participation of PS I, and anoxygenically by PS I (renamed the
      anoxygenic photosystem). It also indicates that plastocyanin is not only, as the
      Z scheme asserts, the electron donor to the reaction center chlorophyll of PS I
      (P700) but also to the reaction center chlorophyll of PS II (P680). Other
      unconventional findings include evidence that the fully functional oxygenic
      photosystem, when operating separately from the anoxygenic photosystem, reduces
      plastoquinone to plastoquinol and subsequently oxidizes plastoquinol by two
      pathways acting in concert: one being the universally recognized DBMIB-sensitive
      pathway via the Rieske iron-sulfur center of the cytochrome bf complex and the
      other, a hitherto unrecognized, DBMIB-insensitive electron transport pathway
      around P680 that centers on cytochrome b-559. These nonconforming findings form
      the basis of an alternate hypothesis of photosynthetic electron transport that
      modifies and complements the Z scheme. 

PMID- 24301569
TI  - Photosynthetic phosphorylation.
AB  - A brief history of the discovery of photosynthetic phosphorylation by
      chloroplasts and bacterial chromatophores is presented. Arnon early introduced
      the terminology of 'Cyclic' and 'Non-cyclic photophosphorylation' and 'Cyclic'
      and 'Non-Cyclic electron transport' to the processes observed in illuminated
      chloroplasts. He made major contributions to the elucidation of these processes
      and stressed their great biological significance. Investigations of the electron
      transport components of chromatophores have led to the isolation, purification
      and crystallization of bacterial reaction centers. The development of three
      dimensional molecular structures, and the characterization of their electron
      transfer components have provided a great deal of information about the early
      reactions of bacterial photosynthesis. The electron transfer schemes presented
      clearly support the 'cyclic' nature of light-induced electron transfer. Recent
      developments in the understanding of ATP synthesis in oxidative phosphorylation
      by mitochondria and in photophosphorylation by chloroplasts and bacterial
      chromatophores are discussed. 

PMID- 24301570
TI  - The photosynthetic F1-alpha 3beta 3 and alpha 1beta 1 catalytic core complexes.
AB  - Minimal photosynthetic catalytic F1(alphabeta) core complexes, containing
      equimolar ratios of the alpha and beta subunits, were isolated from membrane
      bound spinach chloroplast CF1 and Rhodospirillum rubrum chromatophore RrF1. A CF1
      alpha3beta3 hexamer and RrF1-alpha1beta1 dimer, which were purified from the
      respective F1(alphabeta) complexes, exhibit lower rates and different properties
      from their parent F1-ATPases. Most interesting is their complete resistance to
      inhibition by the general F1 inhibitor azide and the specific CF1 inhibitor
      tentoxin. These inhibitors were earlier reported to inhibit multisite, but not
      unisite, catalysis in all sensitive F1-ATPases and were therefore suggested to
      block catalytic site cooperativity. The absence of this typical property of all
      F1-ATPases in the alpha1beta1 dimer is consistant with the view that the dimer
      contains only a single catalytic site. The alpha3beta3 hexamer contains however
      all F1 catalytic sites. Therefore the observation that CF1-alpha3beta3 can bind
      tentoxin and is stimulated by it suggests that the F1gamma subunit, which is
      required for obtaining inhibition by tentoxin as well as azide, plays an
      important role in the cooperative interactions between the F1-catalytic sites. 

PMID- 24301571
TI  - Alternative photophosphorylation, inorganic pyrophosphate synthase and inorganic
      pyrophosphate.
AB  - This minireview in memory of Daniel I. Arnon, pioneer in photosynthesis research,
      concerns properties of the first and still only known alternative
      photophosphorylation system, with respect to the primary phosphorylated end
      product formed. The alternative to adenosine triphosphate (ATP), inorganic
      pyrophosphate (PPi), was produced in light, in chromatophores from the
      photosynthetic bacterium Rhodospirillum rubrum, when no adenosine diphosphate
      (ADP) had been added to the reaction mixture (Baltscheffsky H et al. (1966)
      Science 153: 1120-1122). This production of PPi and its capability to drive
      energy requiring reactions depend on the activity of a membrane bound inorganic
      pyrophosphatase (PPase) (Baltscheffsky M et al. (1966) Brookhaven Symposia in
      Biology, No. 19, pp 246-253); (Baltscheffsky M (1967) Nature 216: 241-243), which
      pumps protons (Moyle J et al. (1972) FEBS Lett 23: 233-236). Both enzyme and
      substrate in the PPase (PPi synthase) are much less complex than in the case of
      the corresponding adenosine triphosphatase (ATPase, ATP synthase). Whereas an
      artificially induced proton gradient alone can drive the synthesis of PPi, both a
      proton gradient and a membrane potential are required for obtaining ATP. The
      photobacterial, integrally membrane bound PPi synthase shows immunological cross
      reaction with membrane bound PPases from plant vacuoles (Nore BF et al. (1991)
      Biochem Biophys Res Commun 181: 962-967). With antibodies against the purified
      PPi synthase clones of its gene have been obtained and are currently being
      sequenced. Further structural information about the PPi synthase may serve to
      elucidate also fundamental mechanisms of electron transport coupled
      phosphorylation. The existence of the PPi synthase is in line with the assumption
      that PPi may have preceded ATP as energy carrier between energy yielding and
      energy requiring reactions. 

PMID- 24301572
TI  - Cryptomonad biliproteins - an evolutionary perspective.
AB  - Each cryptomonad strain contains only a single spectroscopic type of biliprotein.
      These biliproteins are isolated as ~50000 kDa alphaalpha'beta2 complexes which
      carry one bilin on the alpha and three on the beta subunit. Six different bilins
      are present on the cryptomonad biliproteins, two of which (phycocyanobilin and
      phycoerythrobilin) also occur in cyanobacterial and rhodophytan biliproteins,
      while four are known only in the cryptomonads. The beta subunit is encoded on the
      chloroplast genome, whereas the alpha subunits are encoded by a small nuclear
      multigene family. The beta subunits of all cryptomonad biliproteins, regardless
      of spectroscopic type, have highly conserved amino acid sequences, which show >
      80% identity with those of rhodophytan phycoerythrin beta subunits. In contrast,
      cyanobacteria and red algal chloroplasts each contain several spectroscopically
      distinct biliproteins organized into macromolecular complexes (phycobilisomes).
      The data on biliproteins, as well as several other lines of evidence, indicate
      that the cryptomonad biliprotein antenna system is 'primitive' and antedates that
      of the cyanobacteria. It is proposed that the gene encoding the cryptomonad
      biliprotein beta subunit is the ancestral gene of the gene family encoding
      cyanobacterial and rhodophytan biliprotein alpha and beta subunits. 

PMID- 24301573
TI  - Three iron-sulfur proteins encoded by three ORFs in chloroplasts and
      cyanobacteria.
AB  - A brief review is presented on the gene products of frxA, frxB and frxC found in
      chloroplasts. The product of frxA shows high sequence homologies to bacterial
      2[4Fe-4S] ferredoxins, but it functions as iron-sulfur centers A and B in
      Photosystem I, transferring electrons to [2Fe-2S] ferredoxin. This protein is
      located on surface of the thylakoid membranes in a state being covered by two
      other proteins. Proteins homologous to frxB product are found in mitochondrial
      respiratory Complex I and the product of frxB may function in chlororespiration,
      but at present no clear function of this protein is known. The frxC gene product
      is found to function in light-independent chlorophyll synthesis as one of the
      subunits of protochlorophyllide reductase and is reviewed in comparison to
      nitrogenase. Several problems and future research direction in these areas are
      also presented. 

PMID- 24301574
TI  - Integration of photosynthetic carbon and nitrogen metabolism in higher plants.
AB  - Concomitant assimilation of C and N in illuminated leaves requires the regulated
      partitioning of reductant and photosynthate to sustain the demands of amino acid
      and carbohydrate biosynthesis. The short-term responses of photosynthesis and
      photosynthate partitioning to N enrichment in wheat (Triticum aestivum, L.) and
      maize (Zea mays L.) leaves were studied in order to understand the regulatory
      strategy employed in higher plants. Transgenic tobacco plants (Tobacco
      plumbaginifolia) over-expressing NR or with poor NR expression were used to
      compare plants differing in their capacities for NO3 (-) assimilation. Similar
      regulatory responses to NO3 (-) were observed in leaves having C4- and C3-type
      photosynthesis. It was shown that the extra- C needed in the short-term to
      sustain amino acid synthesis was not provided by an increase in photosynthetic
      CO2 fixation but rather by a rapid shift in the partitioning of photosynthetic C
      to amino acid at the expense of sucrose biosynthesis. The modulation of three
      enzymes was shown to be important in this C and N interaction, namely PEPCase (EC
      4.1.1.31), SPS (EC 2.4.1.14) and NADH/NR (EC 1.6.6.1). The first two enzymes were
      shown to share the common feature of regulatory post-transcriptional NO3 (-)
      dependent phosphorylation of their proteins on a seryl-residue. While PEPCase is
      activated, SPS activity is decreased. In contrast the NR phosphorylation state is
      unchanged and all N-dependent control of NR activity is regulated at the protein
      level. A number of arguments support the hypothesis that Gln, the primary product
      of NO3 (-) assimilation, is the metabolite effector for short-term modulation of
      PEPCase, and SPS in response to N enrichment. Since a major effect of NO3 (-) on
      the PEPCase-protein kinase activity in concentrated wheat leaf extracts was
      demonstrated, the hypothesis is put forward that protein phosphorylation is the
      primary event allowing the short-term adaptation of leaf C metabolism to changes
      in N supply. 

PMID- 24301575
TI  - The grand design of photosynthesis: Acclimation of the photosynthetic apparatus
      to environmental cues.
AB  - Dynamic acclimation of the photosynthetic apparatus in response to environmental
      cues, particularly light quantity and quality, is a widely-observed and important
      phenomenon which contributes to the tolerance of plants against stress and helps
      to maintain, as far as possible, optimal photosynthetic efficiency and resource
      utilization. This mini-review represents a scrutiny of a number of possible
      photoreceptors (including the two photosystems acting as light sensors) and
      signal transducers that may be involved in producing acclimation responses. We
      suggest that regulation by signal transduction may be effected at each of several
      possible points, and that there are multiple regulatory mechanisms for
      photosynthetic acclimation. 

PMID- 24301576
TI  - The structure and function of the chloroplast photosynthetic membrane - a model
      for the domain organization.
AB  - Recent work on the domain organization of the thylakoid is reviewed and a model
      for the thylakoid of higher plants is presented. According to this model the
      thylakoid membrane is divided into three main domains: the stroma lamellae, the
      grana margins and the grana core (partitions). These have different biochemical
      compositions and have specialized functions. Linear electron transport occurs in
      the grana while cyclic electron transport is restricted to the stroma lamellae.
      This model is based on the following results and considerations. (1) There is no
      good candidate for a long-range mobile redox carrier between PS II in the grana
      and PS I in the stroma lamellae. The lateral diffusion of plastoquinone and
      plastocyanin is severely restricted by macromolecular crowding in the membrane
      and the lumen respectively. (2) There is an excess of 14+/-18% chlorophyll
      associated with PS I over that of PS II. This excess is assumed to be localized
      in the stroma lamellae where PS I drives cyclic electron transport. (3) For
      several plant species, the stroma lamellae account for 20+/-3% of the thylakoid
      membrane and the grana (including the appressed regions, margins and end
      membranes) for the remaining 80%. The amount of stroma lamellae (20%) corresponds
      to the excess (14-18%) of chlorophyll associated with PS I. (4) The model
      predicts a quantum requirement of about 10 quanta per oxygen molecule evolved,
      which is in good agreement with experimentally observed values. (5) There are at
      least two pools of each of the following components: PS I, PS II, cytochrome bf
      complex, plastocyanin, ATP synthase and plastoquinone. One pool is in the grana
      and the other in the stroma compartments. So far, it has been demonstrated that
      the PS I, PS II and cytochrome bf complexes each differ in their respective
      pools. 

PMID- 24301577
TI  - The cyanobacterium Synechococcus modulates Photosystem II function in response to
      excitation stress through D1 exchange.
AB  - In this minireview we discuss effects of excitation stress on the molecular
      organization and function of PS II as induced by high light or low temperature in
      the cyanobacterium Synechococcus sp. PCC 7942. Synechococcus displays PS II
      plasticity by transiently replacing the constitutive D1 form (D1:1) with another
      form (D1:2) upon exposure to excitation stress. The cells thereby counteract
      photoinhibition by increasing D1 turn over and modulating PS II function. A
      comparison between the cyanobacterium Synechococcus and plants shows that in
      cyanobacteria, with their large phycobilisomes, resistance to photoinhibition is
      mainly through the dynamic properties (D1 turnover and quenching) of the reaction
      centre. In contrast, plants use antenna quenching in the light-harvesting complex
      as an important means to protect the reaction center from excessive excitation. 

PMID- 24301578
TI  - The potential applications of cyanobacterial photosynthesis for clean
      technologies.
AB  - Natural photosynthesis may be adapted to advantage in the development of clean
      energy technologies. Efficient biocatalysts that can be used in solar energy
      conversion technologies are the cyanobacteria. Photobioreactors incorporating
      cyanobacteria have been used to demonstrate (a) the production of hydrogen gas,
      (b) the assimilation of CO2 with the production of algal biomass, (c) the
      excretion of ammonium, and (d) the removal of nitrate and phosphate from
      contaminated waters. 

PMID- 24301579
TI  - An integration of photosynthetic traits and mechanisms that can increase crop
      photosynthesis and grain production.
AB  - The hypothesis we propose is that during photosynthesis the balance between
      potentially detrimental and beneficial photochemically induced events can be
      tipped beneficially toward increased photosynthesis and toward increased crop
      yield. To test this hypothesis a procedure has been devised with the rice plant,
      Oryza sativa, that has resulted in increasing both canopy photosynthesis and rice
      grain yield. Two elite rice varieties selected independently in the contrasting
      environments of either South China or Texas, each with distinct photosynthetic
      traits, were crossed to produce a hybrid with an increased canopy photosynthesis
      and grain yield that is regularly 20 to 22% higher than the mid-yields of the
      parents. The photosynthetic and mechanisms which may contribute to these
      beneficial results in the hybrid rice are: a reduction of the midday depression
      of photosynthesis; a rapid development of the canopy for photosynthetic light
      interception and an increased canopy photosynthesis; increased amounts of
      carotenoids for the xanthophyll cycle; an increased protection against free
      radicals induced by paraquat treatment; a 6 to 12 day shorter plant reproductive
      life cycle; and a 8 to 10 day increase in the longevity of the flag leaf over the
      parents. While the hybrid rice has successfully integrated these and likely other
      unknown characteristics to increase both crop photosynthesis and grain yield, we
      propose that understanding the underlying beneficial photosynthetic mechanisms
      supporting these crop plant traits is worthy of thorough investigation and
      application in crop production. 

PMID- 24301580
TI  - A hydrogen-atom abstraction model for the function of YZ in photosynthetic oxygen
      evolution.
AB  - Recent magnetic-resonance work on YZ suggests that this species exhibits
      considerable motional flexibility in its functional site and that its phenol
      oxygen is not involved in a well-ordered hydrogen-bond interaction (Tang et al.,
      submitted; Tommos et al., in press). Both of these observations are inconsistent
      with a simple electron-transfer function for this radical in photosynthetic water
      oxidation. By considering the roles of catalytically active amino acid radicals
      in other enzymes and recent data on the water-oxidation process in Photosystem
      II, we rationalize these observations by suggesting that YZ functions to abstract
      hydrogen atoms from aquo- and hydroxy-bound managanese ions in the (Mn)4 cluster
      on each S-state transition. The hydrogen-atom abstraction process may occur
      either by sequential or concerted kinetic pathways. Within this model, the
      (Mn)4/YZ center forms a single catalytic center that comprises the Oxygen
      Evolving Complex in Photosystem II. 

PMID- 24301581
TI  - pH-dependent photoreactions of the high- and low-potential forms of cytochrome
      b559 in spinach PS II-enriched membranes.
AB  - Cytochrome b559 (Cyt b559) is a well-known intrinsic component of Photosystem II
      (PS II) reaction center in all photosynthetic oxygen-evolving organisms, but its
      physiological role remains unclear. This work reports the response of the two
      redox forms of Cyt b559 (i.e. the high- (HP) and low-potential (LP) forms) to
      inhibition of the donor or acceptor side of PS II. The photooxidation of HP Cyt
      b559 induced by red light at room temperature was pH-dependent under conditions
      in which electron flow from water was diminished. This photooxidation was
      observed only at pH values higher than 7.5. However, in the presence of 1 MUM
      CCCP, a limited oxidation of HP Cyt b559 was observed at acidic pH, At pH 8.5 and
      in the presence of the protonophore, this photooxidation of the HP form was
      accompanied by its partial transformation into the LP form. On the other hand, a
      partial photoreduction of LP Cyt b559 was induced by red light under aerobic
      conditions when electron transfer through the primary quinone acceptor QA was
      impaired by strong irradiation in the presence of DCMU. This photoreduction was
      enhanced at acidic pH values. To the best of our knowledge, this is the first
      time that both photoreduction and photooxidation of Cyt b559 is described under
      inhibitory conditions using the same kind of membrane preparations. A model
      accommodating these findings is proposed. 

PMID- 24301582
TI  - pH sensitivity of the redox state of cytochrome b559 may regulate its function as
      a protectant against donor and acceptor side photoinhibition.
AB  - A series of experiments have been conducted with isolated reaction centers of
      photosystem two (PS II) with the aim to elucidate the functional role of
      cytochrome (Cyt b 559). At pH 6.5 it was found that Cyt b 559 was reversibly
      photoreduced by red actinic light when Mn(2+) was present as an electron donor
      while at pH 8.5 a photo-oxidation was observed under the same lighting
      conditions, which was dark reversible in the presence of hydroquinone. These pH
      dependent light induced changes were measured under anaerobic conditions and
      correlated with changes in the relative levels of high (HP) and low (LP)
      potential forms of the cytochrome. At pH 6.5 the cytochrome was mainly in its LP
      form while at pH 8.5 a significant proportion was converted to the HP form as
      detected by dark titrations with hydroquinone. This pH dependent difference in
      the levels of HP and LP Cyt b 559 was also detected when bright white light was
      used to monitor the level of the LP form using a novel reaction involving direct
      electron donation from the flavin of glucose oxidase (present in the medium and
      used together with glucose and catalase as an oxygen trap). The results suggest
      that PS II directly oxidises and reduces the HP and LP forms, respectively and
      that the extent of these photo-reactions is dependent on the relative levels of
      the two forms, which are in turn governed by the pH. This conclusion is
      interpreted in terms of the model presented previously (Barber J and De Las Rivas
      J (1993) Proc Natl Acad Sci USA 90: 10942-10946) whereby the pH induced effect is
      considered as a possible mechanism by which interconversion of LP and HP forms of
      Cyt b 559 is achieved. In agreement with this was the finding that as the extent
      of photo-oxidisable HPCyt b 559 increases, with increasing pH, the rate of
      irreversible photo-oxidation of beta-carotene decreases, a result expected if the
      HP form protects against donor side photoinhibition. 

PMID- 24301583
TI  - Effect of back reactions in the S-cycle on photosynthesis in very weak light.
AB  - Photosynthesis in light which is so weak that excitation rates are comparable to
      the decay rates of S-states is modelled. It is found that oxygen evolution rate
      varies in a non-linear way with Photosystem II excitation rate in this region,
      but asymptotically approaches a linear relationship (with a slope of one oxygen
      molecule per four excitations) as excitation rate increases. The asymptote gives
      an intercept (zero oxygen evolution rate) on the excitation rate axis. The
      question is raised, whether this model is compatible with photoautotrophy in a
      red alga found at 268 m depth and able to carry out photosynthesis in extremely
      weak light. It is found that no unorthodox mechanisms for the S-cycle in this
      alga have to be assumed to explain its performance. 

PMID- 24301584
TI  - Characterization of a 160 kD Photosystem II reaction center complex isolated from
      photoinhibited Dunaliella salina thylakoids.
AB  - Photoinhibition in the green alga Dunaliella salina is accompanied by the
      formation of inactive Photosystem II reaction centers. In SDS-PAGE analysis, the
      latter appear as 160 kD complexes. These complexes are structurally stable,
      enough to withstand re-electrophoresis of excised gel slices from the 160 kD
      region. Western blot analyses with specific polyclonal antibodies raised against
      the D1 or D2 reaction center proteins provided evidence for the presence of both
      of these polypeptides in the re-electrophoresed 160 kD complex. Incubation of
      excised gel slices from the 160 kD region, under aerobic conditions at 4 degrees
      C for a prolonged period of time, caused a break-up of the 160 kD complex into a
      ?52 kD D1-containing and ?80 and ?26 kD D2-containing pieces. Western blot
      analysis with polyclonal antibodies raised against the apoproteins of CPI
      (reaction center proteins of PS I) did not show cross-reaction either with the
      160 kD complex or with the ?52, ?80 and ?26 kD pieces. The results show the
      presence of both D1 and D2 in the 160 kD complex and strengthen the notion of a
      higher molecular weight D1- and D2-containing complex that forms upon disassembly
      of photodamaged PS II units. 

PMID- 24301585
TI  - Comparative EPR and thermoluminescence study of anoxic photoinhibition in
      Photosystem II particles.
AB  - Photosystem II particles were exposed to 800 W m(-2) white light at 20  degrees C
      under anoxic conditions. The Fo level of fluorescence was considerably enhanced
      indicating formation of stable-reduced forms of the primary quinone electron
      acceptor, QA. The Fm level of fluorescence declined only a little. The g=1.9 and
      g=1.82 EPR forms characteristic of the bicarbonate-bound and bicarbonate-depleted
      semiquinone-iron complex, QA (-)Fe(2+), respectively, exhibited differential
      sensitivity against photoinhibition. The large g=1.9 signal was rapidly
      diminished but the small g=1.82 signal decreased more slowly. The S2-state
      multiline signal, the oxygen evolution and photooxidation of the high potential
      form of cytochrome b-559 were inhibited approximately with the same kinetics as
      the g=1.9 signal. The low potential form of oxidized cytochrome b-559 and Signal
      IIslow arising from TyrD (+) decreased considerably slower than the g=1.9
      semiquinone-iron signal. The high potential form of oxidized cytochrome b-559 was
      diminished faster than the low potential form. Photoinhibition of the g=1.9 and
      g=1.82 forms of QA was accompanied with the appearance and gradual saturation of
      the spin-polarized triplet signal of P 680. The amplitude of the radical signal
      from photoreducible pheophytin remained constant during the 3 hour illumination
      period. In the thermoluminescence glow curves of particles the Q band (S2QA (-)
      charge recombination) was almost completely abolished. To the contrary, the C
      band (TyrD (+)QA (-) charge recombination) increased a little upon illumination.
      The EPR and thermoluminescence observations suggest that the Photosystem II
      reaction centers can be classified into two groups with different susceptibility
      against photoinhibition. 

PMID- 24301586
TI  - Effects of bicarbonate and formate on the donor side of Photosystem 2.
AB  - Sodium formate at concentration of 5-20 MUM suppresses electron flow on the donor
      side of Photosystem 2 (PS 2) in pea subchloroplast membranes (DT-20) which is
      revealed by inhibition of photoinduced changes of chlorophyll fluorescence yield
      related to photoreduction of QA and pheophytin (the primary and intermediary
      electron acceptors) and oxygen evolution and the increase of absorbance changes
      related to photooxidation of P680, the primary electron donor, under continuous
      illumination. These activities are also inhibited upon partial depletion of
      bicarbonate in the medium and restored by the addition of 0.1-10 mM NaHCO3. At
      concentrations higher than 20 MUM formate induces the known bicarbonate effect on
      the acceptor side of PS 2 which dominates at millimolar concentrations of the
      agent. In Tris-treated (Mn-depleted) DT-20 the restoration of electron flow with
      0.2 MUM MnCl2 (4 Mn atoms per one PS 2 reaction center) in the medium depleted of
      bicarbonate is efficient only after the addition of 5 mM NaHCO3. The restoration
      in the presence of NaHCO3 is accompanied by an increased functional binding of
      Mn(2+) to PS 2 membranes which is confirmed by experiments on removal of added
      Mn(2+) by either sedimentation or the addition of EDTA. Pre-illumination
      increases the Mn binding in the presence of bicarbonate. The data show that the
      bicarbonate effect on the donor side of PS 2 is related to a relatively low
      affinity bound pool of bicarbonate. It is suggested that bicarbonate takes part
      in the formation of the Mn-cluster capable of water oxidation as an obligatory
      ligand or through modification of the binding site(s) of Mn. 

PMID- 24301587
TI  - Photosystem II acclimation to limiting growth light in fully developed leaves of
      Amaranthus hypochondriacus L., an NAD-ME C4 plant.
AB  - A remarkable acclimation strategy was exhibited by Photosystem II when fully
      mature Amaranthus hypochondriacus L. plants grown at light sufficient (2000 MUE
      m(-2) s(-1)) conditions were transferred to light limited environment (650 MUE m(
      2) s(-1)). There was a two pronged response of PS II to low growth light both by
      way of modulating the size of LHC II to offset the decrease in excitation energy
      capture and by decreased synthesis of reaction centre protein, D1 the later
      through depressed level of transcription of psbA gene. The molecular regulation
      of PS II under low light stress is discussed. 

PMID- 24301588
TI  - A 43 kD light-regulated chloroplast RNA-binding protein interacts with the psbA
      5' non-translated leader RNA.
AB  - Expression of the chloroplast psbA gene coding for the D1 protein of Photosystem
      II is subject to regulation at different levels in higher plants, including
      control of mRNA accumulation and translation. In dicots, the conserved 5' non
      translated leader (5'-UTR) of the psbA mRNA is sufficient to direct the light
      dependent translation of the D1 protein. In this report we show that the psbA
      mRNA 5'-UTR forms a stem-loop structure and binds a 43 kD chloroplast protein
      (43RNP). Binding of the 43RNP is sensitive to competition with poly(U), but
      insensitive to high concentrations of tRNA, the RNA homopolymers poly(A),
      poly(G), poly(C), or poly(A):poly(U) as a double-strand RNA. The 43RNP does not
      bind efficiently to the psbA mRNA 3' non-translated region, although the RNA
      sequence is U-rich and folds into a stem-loop. A deletion mutant of the psbA 5'
      UTR RNA in which 5' sequences of the stem-loop are removed does not affect 43RNP
      binding. Together, these properties suggest that the 43RNP binds most effectively
      to a specific single-strand U-rich sequence preceding the AUG start codon in the
      psbA mRNA. Binding of the 43RNP is not detectable in plastid protein extracts
      from 5-day-old dark-grown seedlings, but is detectable in light-grown seedlings
      as well as mature plants in the light and after shifted to the dark. The 43RNP is
      therefore a candidate for a regulatory RNA-binding protein that may control the
      accumulation and/or translation of the psbA mRNA during light-dependent seedling
      development. 

PMID- 24301589
TI  - Reconstitution of iron-sulfur center FB results in complete restoration of NADP
      (+) photoreduction in Hg-treated Photosystem I complexes from Synechococcus sp.
      PCC 6301.
AB  - The FB iron-sulfur cluster is destroyed preferentially by treating Photosystem I
      complexes with HgCl2(Kojima Y, Niinomi Y, Tsuboi S, Hiyama T and Sakurai H (1987)
      Bot Mag 100: 243-53). When FB is 95% depleted but FAis quantitatively retained in
      cyanobacterial PS I complexes, the reduction potential of FA remains highly
      electronegative (Em=-530 mV, n=1), the EPR spectral and spin relaxation
      properties of FA and FXremain unchanged, but NADP(+) photoreduction rates decline
      from 552 to 72 MUmol mg Chl(-1) h(-1).When FB is reconstituted with FeCl3, Na2S
      and beta-mercaptoethanol, NADP(+)photoreduction rates recover to 528 MUmol mg
      Chl(-1) h(-1). The correlation between the presence of FBand NADP(+)
      photoreduction provides direct experimental evidence that this iron-sulfur
      cluster is required for electron throughput from cytochromec 6 to flavodoxin or
      ferredoxin in Photosystem I. 

PMID- 24301590
TI  - Analysis of the proposed Fe-SX binding region of Photosystem 1 by site directed
      mutation of PsaA in Chlamydomonas reinhardtii.
AB  - The psaA and psaB genes of the chloroplast genome in oxygenic photosynthetic
      organisms code for the major peptides of the Photosystem 1 reaction center. A
      heterodimer of the two polypeptides PsaA and PsaB is thought to bind the reaction
      center chlorophyll, P700, and the early electron acceptors A0, A1 and Fe-SX. Fe
      SX is a 4Fe4S center requiring 4 cysteine residues as ligands from the protein.
      As PsaA and PsaB have only three and two conserved cysteine residues
      respectively, it has been proposed by several groups that Fe-SX is an unusual
      inter-peptide center liganded by two cysteines from each peptide. This hypothesis
      has been tested by site directed mutagenesis of PsaA residue C575 and the
      adjacent D576. The C575D mutant does not assemble Photosystem 1. The C575H mutant
      contains a photoxidisable chlorophyll with EPR properties of P700, but no other
      Photosystem 1 function has been detected. The D576L mutant assembles a modified
      Photosystem 1 in which the EPR properties of the Fe-SA/B centers are altered. The
      results confirm the importance of the conserved cysteine motif region in
      Photosystem 1 structure. 

PMID- 24301591
TI  - Nucleotide sequence of the psaD gene from the thermophilic cyanobacterium
      Synechococcus vulcanus.
AB  - The nucleotide sequence was determined for the psaD gene of a thermophilic
      cyanobacterium, Synechococcus vulcanus, which encoded the PsaD subunit (Subunit
      II) of the Photosystem I reaction center complex. Except for some differences in
      the peripherals, the nucleotide sequence of the gene encoding PsaD was identical
      to that of another thermophilic cyanobacterium Synechococcus elongatus reported
      previously. Relationship between these primary structures and thermostability was
      also discussed. 

PMID- 24301592
TI  - Coupled cyclic electron transport in intact chloroplasts and leaves of C3 plants:
      Does it exist? if so, what is its function?
AB  - Transthylakoid proton transport based on Photosystem I-dependent cyclic electron
      transport has been demonstrated in isolated intact spinach chloroplasts already
      at very low photon flux densities when the acceptor side of Photosystem I (PS I)
      was largely closed. It was under strict redox control. In spinach leaves, high
      intensity flashes given every 50 s on top of far-red, but not on top of red
      background light decreased the activity of Photosystem II (PS II) in the absence
      of appreciable linear electron transport even when excitation of PS II by the
      background light was extremely weak. Downregulation of PS II was a consequence of
      cyclic electron transport as shown by differences in the redox state of P700 in
      the absence and the presence of CO2 which drained electrons from the cyclic
      pathway eliminating control of PS II. In the presence of CO2, cyclic electron
      transport comes into play only at higher photon flux densities. At H(+)/e=3 in
      linear electron transport, it does not appear to contribute much ATP for carbon
      reduction in C3 plants. Rather, its function is to control the activity of PS II.
      Control is necessary to prevent excessive reduction of the electron transport
      chain. This helps to protect the photosynthetic apparatus of leaves against
      photoinactivation under light stress. 

PMID- 24301593
TI  - Light adaptation of cyclic electron transport through Photosystem I in the
      cyanobacterium Synechococcus sp. PCC 7942.
AB  - Photosystem I-driven cyclic electron transport was measured in intact cells of
      Synechococcus sp PCC 7942 grown under different light intensities using
      photoacoustic and spectroscopic methods. The light-saturated capacity for PS I
      cyclic electron transport increased relative to chlorophyll concentration, PS I
      concentration, and linear electron transport capacity as growth light intensity
      was raised. In cells grown under moderate to high light intensity, PS I cyclic
      electron transport was nearly insensitive to methyl viologen, indicating that the
      cyclic electron supply to PS I derived almost exclusively from a thylakoid
      dehydrogenase. In cells grown under low light intensity, PS I cyclic electron
      transport was partially inhibited by methyl viologen, indicating that part of the
      cyclic electron supply to PS I derived directly from ferredoxin. It is proposed
      that the increased PSI cyclic electron transport observed in cells grown under
      high light intensity is a response to chronic photoinhibition. 

PMID- 24301594
TI  - The role of phospholipids in regulating photosynthetic electron transport
      activities: Treatment of thylakoids with phospholipase C.
AB  - The involvement of phospholipids in the regulation of photosynthetic electron
      transport activities was studied by incubating isolated pea thylakoids with
      phospholipase C to remove the head-group of phospholipid molecules. The treatment
      was effective in eliminating 40-50% of chloroplast phospholipids and resulted in
      a drastic decrease of photosynthetic electron transport. Measurements of whole
      electron transport (H2O->methylviologen) and Photosystem II activity (H2O->p
      benzoquinone) demonstrated that the decrease of electron flow was due to the
      inactivation of Photosystem II centers. The variable part of fluorescence
      induction measured in the absence of electron acceptor was decreased by the
      progress of phospholipase C hydrolysis and part of the signal could be restored
      on addition of 3-(3',4'-dicholorophenyl)-1,1-dimethylurea. The B and Q bands of
      thermoluminescence corresponding to S2S3QB (-) and S2S3QA (-) charge
      recombination, respectively, was also decreased with a concomitant increase of
      the C band, which originated from the tyrosine D(+)QA (-) charge recombination.
      These results suggest that phospholipid molecules play an important role in
      maintaining the membrane organization and thus maintaining the electron transport
      activity of Photosystem II complexes. 

PMID- 24301595
TI  - Effects of dehydration on the electron transport of Chlorella. An in vivo
      fluorescence study.
AB  - Chlorella was used to study the effects of dehydration on photosynthetic
      activities. The use of unicellular green algae assured that the extent of
      dehydration was uniform throughout the whole cell population during the course of
      desiccation. Changes in the activities of the cells were monitored by
      measurements of fluorescence induction kinetics. It was found that inhibition of
      most of the photosynthetic activities started at a similar level of cellular
      water content. They included CO2 fixation, photochemical activity of Photosystem
      II and electron transport through Photosystem I. The blockage of electron flow
      through Photosystem I was complete and the whole transition occurred within a
      relative short time of dehydration. On the other hand, the suppression of
      Photosystem II activity was incomplete and the transition took a longer time of
      dehydration. Upon rehydration, the inhibition of Photosystem II activity was
      fully reversible when samples were in the middle of the transition, but was not
      thereafter. The electron transport through Photosystem I was also reversible
      during the transition, but was only partially afterward. 

PMID- 24301596
TI  - Amino acid sequences of heterotrophic and photosynthetic ferredoxins from the
      tomato plant (Lycopersicon esculentum Mill.).
AB  - Several forms (isoproteins) of ferredoxin in roots, leaves, and green and red
      pericarps in tomato plants (Lycopersicon esculentum Mill.) were earlier
      identified on the basis of N-terminal amino acid sequence and chromatographic
      behavior (Green et al. 1991). In the present study, a large scale preparation
      made possible determination of the full length amino acid sequence of the two
      ferredoxins from leaves. The ferredoxins characteristic of fruit and root were
      sequenced from the amino terminus to the 30th residue or beyond. The leaf
      ferredoxins were confirmed to be expressed in pericarp of both green and red
      fruit. The ferredoxins characteristic of fruit and root appeared to be restricted
      to those tissue. The results extend earlier findings in demonstrating that
      ferredoxin occurs in the major organs of the tomato plant where it appears to
      function irrespective of photosynthetic competence. 

PMID- 24301597
TI  - Reduction of ferredoxin:thioredoxin reductase by artificial electron donors.
AB  - The ferredoxin:thioredoxin reductase is an essential enzyme of the light
      dependent regulatory system in oxygenic photosynthesis. It is composed of two
      dissimilar subunits and contains a 4Fe-4S cluster and a redox-active disulfide
      bridge. Artificial electron donors of redox potentials below -300 mV are capable
      of reducing the disulfide bridge. Based on our results we speculate that a group
      of more negative potential than the disulfide bridge is the first acceptor of the
      electrons in FTR. The chemical reduction of FTR has been used successfully for
      the detection of the enzyme during its purification. 

PMID- 24301598
TI  - High level expression in Escherichia coli, purification and properties of
      chloroplast fructose-1,6-bisphosphatase from rapeseed (Brassica napus) leaves.
AB  - In chloroplasts, the light-modulated fructose-1,6-bisphosphatase catalyzes the
      formation of fructose 6-bisphosphate for the photosynthetic assimilation of CO2
      and the biosynthesis of starch. We report here the construction of a plasmid for
      the production of chloroplast fructose-1,6-bisphosphatase in a bacterial system
      and the subsequent purification to homogeneity of the genetically engineered
      enzyme. To this end, a DNA sequence that coded for chloroplast fructose-1,6
      bisphosphatase of rapeseed (Brassica napus) leaves was successively amplified by
      PCR, ligated into the Ndel/EcoRI restriction site of the expression vector
      pET22b, and introduced into Escherichia coli cells. When gene expression was
      induced by isopropyl-beta-D-thiogalactopyranoside, supernatants of cell lysates
      were extremely active in the hydrolysis of fructose 1,6-bisphosphate.
      Partitioning bacterial soluble proteins by ammonium sulfate followed by anion
      exchange chromatography yielded 10 mg of homogeneous enzyme per 1 of culture.
      Congruent with a preparation devoid of contaminating proteins, the Edman
      degradation evinced an unique N-terminal amino acid sequence [A-V-A-A-D-A-T-A-E-T
      K-P-]. Gel filtration experiments and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis indicated that the (recombinant) rapeseed chloroplast fructose
      1,6-bisphosphatases was a tetramer [160 kDa] comprised of four identical
      subunits. Like other chloroplast fructose-1,6-bisphosphatases, the recombinant
      enzyme was inactive at 1 mM fructose 1,6-bisphosphate and 1 mM Mg(2+) but became
      fully active after an incubation in the presence of either 10 mM dithiothreitol
      or 1 mM dithiothreitol and chloroplast thioredoxin. However, at variance with
      counterparts isolated from higher plant leaves, the low activity observed in
      absence of reductants was not greatly enhanced by high concentrations of fructose
      1,6-bisphosphate (3 mM) and Mg(2+) (10 mM). In the catalytic process, all
      chloroplast fructose-1,6-bisphosphatases had identical features; viz., the
      requirement of Mg(2+) as cofactor and the inhibition by Ca(2+). Thus, the
      procedure described here should prove useful for the structural and kinetic
      analysis of rapeseed chloroplast fructose-1,6-bisphosphatase in view that this
      enzyme was not isolated from leaves. 

PMID- 24301599
TI  - Mature ferredoxin-NADP reductase with a glutaminyl residue at N-terminus from
      spinach chloroplasts.
AB  - When 35%-acetone extract of spinach chloroplasts was separated by SDS-PAGE,
      ferredoxin-NADP reductase (FNR) appeared as a single band at a molecular mass of
      35 kDa. After the polypeptides on the SDS-PAGE plate were electroblotted onto
      PVDF membrane, the FNR band was cut out and analyzed for N-terminal structure in
      a gas-phase protein sequencer. Two different FNR peptides were identified: one
      with glutamine at its N-terminus (Gln-FNR) and the other with gamma-pyroglutamic
      acid (<Glu-FNR). Next, tightly bound FNR (tFNR) fraction was extracted from
      chloroplasts with their loosely bound FNR (lFNR) fraction removed in advance. The
      tFNR fraction contained Gln-FNR only. The Gln-FNR could be highly purified by
      affinity chromatography using a ferredoxin column. The purified Gln-FNR was
      digested with arginyl endopeptidase for peptide mapping and partial sequence
      analysis. Primary structure of Gln-FNR differed from that of <Glu-FNR previously
      reported by Karplus et al. (1984) only in that it has an unblocked N-terminus.
      Highly purified Gln-FNR gave a molecular mass of 35 kDa in SDS-PAGE analysis, but
      its apparent molecular mass was estimated to be 38.5 kDa by gel-filtration HPLC
      analysis. This larger apparent molecular mass of Gln-FNR could be ascribed to its
      N-terminal moiety with around 15 amino acid residues protruding outside of a
      globular FNR molecule. 

PMID- 24301600
TI  - Movement of DNA across the chloroplast envelope: Implications for the transfer of
      promiscuous DNA.
AB  - Little is known about the mechanistic basis for the movement of promiscuous
      nucleic acids across cell membranes. To address this problem we sought conditions
      that would permit the entry of plasmid DNA into isolated, intact pea
      chloroplasts. DNA uptake did not occur normally, but was induced by hypotonic
      treatments, by incubation with millimolar levels of Mg(2+), or by heat shock at
      42  degrees C. These results are consistent with DNA movement being permitted by
      conditions that transiently alter the permeability of the chloroplast envelope.
      Plant cells are subject to osmotic tensions and/or conditions inducing
      polymorphic changes in the membranes, such as those used in the present study,
      under several environmental stresses. In an evolutionary time frame, these
      phenomena may provide a mechanism for the transfer of promiscuous nucleic acids
      between organelles. 

PMID- 24301601
TI  - Perfusion chromatography-a new procedure for very rapid isolation of integral
      photosynthetic membrane proteins.
AB  - The biochemical isolation of pure and active proteins or chlorophyll protein
      complexes has been crucial for elucidating the mechanism of photosynthetic energy
      conversion. Most of the proteins involved in this process are embedded in the
      photosynthetic membrane. The isolation of such hydrophobic integral membrane
      proteins is not trivial, and involves the use of detergents often combined with
      various time-consuming isolation procedures. We have applied the new procedure of
      perfusion chromatography for the rapid isolation of photosynthetic membrane
      proteins. Perfusion chromatography combines a highly reactive surface per bed
      volume with extremely high elution flow rates. We present an overview of this
      chromatographic method and show the rapid isolation of reaction centres from
      plant Photosystems I and II and photosynthetic purple bacteria, as well as the
      fractionation of the chlorophyll a/b-binding proteins of Photosystem I (LHC I).
      The isolation times have been drastically reduced compared to earlier approaches.
      The pronounced reduction in time for separation of photosynthetic complexes is
      convenient and permits purification of proteins in a more native state, including
      the maintainance of ligands and the possibility to isolate proteins trapped in
      intermediate metabolic or structural states. 

PMID- 24301602
TI  - The size of the photosynthetic unit in purple bacteria.
AB  - Pigment analysis was performed by means of normal phase HPLC on a number of
      bacteriochlorophyll a and b containing species of purple bacteria that contain a
      core antenna only. At least 99% of the bacteriochlorophyll in Rhodobacter
      sphaeroides R26, Rhodopseudomonas viridis and Thiocapsa pfennigii was esterified
      with phytol (BChl a p and BChl b p, respectively). Rhodospirillum rubrum
      contained only BChl a esterified with geranyl-geraniol (BChl a GG).
      Rhodospirillum sodomense and Rhodopseudomonas marina contained, in addition to
      BChl a p, small amounts of BChl a GG, and presumably also of BChl a esterified
      with dihydro and tetrahydro geranyl-geraniol (Delta2,10,14-phytatrienol and
      probably Delta2,14-phytadienol). In all species bacteriopheophytin (BPhe)
      esterified with phytol was present. The BChl/BPhe ratio indicated that in these
      species a constant number of 25 +/- 3 antenna BChls is present per reaction
      centre. This number supports a model in which the core antenna consists of 12
      alpha-beta heterodimers surrounding the reaction centre. Determination of the in
      vivo extinction coefficient of BChl in the core-reaction centre complex yielded a
      value of ca. 140 mM(-1) cm(-1) for BChl a containing species and of 130 mM(-1)
      cm(-1) for Rhodopseudomonas viridis. 

PMID- 24301603
TI  - Purification of an LHI-RC-complex of Rhodospirillum rubrum by solubilization of
      chromatophores with a short-chain lecithin.
AB  - Chromatophores from Rhodospirillum rubrum were solubilized using the detergent
      1,2-diheptanoyl-sn-phosphatidylcholine (DHPC). The solubilization curves are
      sigmoidal reaching a plateau at a detergent/protein ratio of 2-3 MUmol/mg
      corresponding to 75-90% solubilized protein. The BChl-binding proteins are stable
      over a large range of DHPC/protein ratios. A complex of BChl-binding proteins
      containing both LHI- and RC-polypeptides (LHI-RC-complex) was purified using a
      two step procedure. RC photochemical activity as well as absorption and near-IR
      CD spectra showed the complex to be active and stable after purification in
      presence of DHPC. 

PMID- 24301604
TI  - The structural role of the carotenoid in the bacterial light-harvesting protein 2
      (LH2) of Rhodonbacter capsulatus. A Fourier transform Raman spectroscopy and
      circular dichroism study.
AB  - In previous work (Zurdo J, Fernandez-Cabrera C and Ramirez JM (1993) Biochem J
      290: 531-537), it had been shown that selective extraction of the carotenoid from
      the light-harvesting protein 2 (LH2) of Rhodobacter capsulatus induced the
      dissociation of 800-nm absorbing bacteriochlorophyll (Bchl), a 10-nm red shift of
      854-nm Bchl, and a decrease of the stability of the protein in detergent
      solution. In the present study, the Fourier transform Raman and near-infrared
      circular dichroism spectra of native and carotenoid-depleted LH2 membrane
      preparations were compared. It was found that while the coupled carbonyls of 854
      nm Bchl remained specifically H-bonded to the peptides after carotenoid
      extraction, the optical activity of the near-infrared electronic transition was
      significantly altered. Given the excitonic origin of such optical activity, our
      data suggest that carotenoid extraction elicits a rearrengement of the
      chromophore cluster and of the associated polypeptide subunits. This implies a
      significant role of the carotenoid in maintaining the native quaternary structure
      of the protein, which would be consistent with the observed dissociation of 800
      nm Bchl and the loss of solubilized LH2 stability that result from carotenoid
      removal. There is no evidence for a similar role of the carotenoid in the LH1
      protein. 

PMID- 24301605
TI  - Amino acid sequence of ferredoxin II from the phototroph Rhodospirillum rubrum:
      Characteristics of a 7Fe ferredoxin.
AB  - The complete sequence of amino acids of ferredoxin II (FdII) from Rhodospirillum
      rubrum was determined by repetitive Edman degradation using pyridylethylated
      ferredoxin and oxidized, denatured ferredoxin. Peptides derived from trypsin,
      pepsin, Glu-C endoproteinase, Arg-C endoproteinase, tryptophan specific cleavage
      and partial acid hydrolysis and C-terminal sequence from carboxypeptidase
      digestion were used to construct the total sequence. RrFdII is a polypeptide of
      104 amino acids having a calculated molecular weight of 11556 excluding the iron
      and sulfur atoms. The complete amino acid sequence was:
      PYVVTENCIKCKYQDCVEVCPVDCFYEGENFLVINPDECIDCGVCNPECPAEAIAGKWLEINRKFADLWPNITRKGPAL
      ADADDWKDKPDKTGLLSENPGKGTV. Sequence comparisons, EPR characteristics and iron
      analyses indicate that RrFdII has structural features in common with ferredoxins
      containing [3Fe-4S], [4Fe-4S] centers. Of 104 amino acids, 60 (58%) including all
      9 cysteines, are found in identical locations in the 7Fe ferredoxin prototype,
      Azotobacter vinelandii FdI. 

PMID- 24301606
TI  - Generation gland morphology in cordylid lizards: an evolutionary perspective.
AB  - To elucidate the functional significance of the three distinct types of
      generation glands that have been identified among cordylid lizards, we mapped
      gland type to the terminal taxa in the most recent phylogenetic tree for the
      Cordylidae. We used the phylogenetic programme Mesquite and applied the principle
      of parsimony to infer character states for the ancestral nodes in the tree. For
      those species where information on gland type was not available from the
      literature, we conducted a histological investigation of generation gland
      morphology, using standard histological techniques. We included two species of
      the sister family Gerrhosauridae in the analysis to serve as outgroups. In both
      Gerrhosaurus typicus and G. flavigularis, scales immediately anterior to the
      femoral pores displayed glandular activity, but differed from generation glands
      of cordylids in the absence of mature glandular generations. Among the cordylids
      investigated, we identified a fourth type of generation gland in Pseudocordylus
      subviridis, P. spinosus, and in the two Hemicordylus species, one where the
      glands consistently comprise of two mature glandular generations. In H. capensis,
      both single- and two-layer type glands are present. Our reconstruction of
      ancestral character states suggests a minimum of six transformations from one
      gland type to another during the evolutionary history of the family. The
      reconstruction furthermore suggests that the single-layer type gland reappeared
      at least once (in Hemicordylus) in the Cordylinae after having been lost. The
      reconstruction also unequivocally shows that the pit-like multiple-layer type
      gland evolved directly from the single-layer type and not from the protruding
      multiple-layer type. The two-layer type gland appears to be an intermediary
      condition between the multiple-layer and single-layer types. The evolutionary
      transformation of generation gland type appears to be linked to changes in
      lifestyle and associated changes in degree of territoriality and the need for
      chemical communication.

PMID- 24301607
TI  - Highly enantioselective hydrogenation of 2-substituted-2-alkenols catalysed by a
      ChenPhos-Rh complex.
AB  - Highly enantioselective hydrogenation of a variety of 2-substituted-2-alkenols
      has been achieved using a ChenPhos-Rh complex as catalyst, giving >=99% ee for
      most substrates. Optically active antifungal agent amorolfine was first
      synthesised using hydrogenation as the key step. 

PMID- 24301608
TI  - Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the
      dihydropyridine dehydrogenation.
AB  - Amlodipine is a commonly prescribed calcium channel blocker for the treatment of
      hypertension and ischemic heart disease. The drug is slowly cleared in humans
      primarily via dehydrogenation of its dihydropyridine moiety to a pyridine
      derivative (M9). Results from clinical drug-drug interaction studies suggest that
      CYP3A4/5 mediate metabolism of amlodipine. However, attempts to identify a role
      of CYP3A5 in amlodipine metabolism in humans based on its pharmacokinetic
      differences between CYP3A5 expressers and nonexpressers failed. Objectives of
      this study were to determine the metabolite profile of amlodipine (a racemic
      mixture and S-isomer) in human liver microsomes (HLM), and to identify the
      cytochrome P450 (P450) enzyme(s) involved in the M9 formation. Liquid
      chromatography/mass spectrometry analysis showed that amlodipine was mainly
      converted to M9 in HLM incubation. M9 underwent further O-demethylation, O
      dealkylation, and oxidative deamination to various pyridine derivatives. This
      observation is consistent with amlodipine metabolism in humans. Incubations of
      amlodipine with HLM in the presence of selective P450 inhibitors showed that both
      ketoconazole (an inhibitor of CYP3A4/5) and CYP3cide (an inhibitor of CYP3A4)
      completely blocked the M9 formation, whereas chemical inhibitors of other P450
      enzymes had little effect. Furthermore, metabolism of amlodipine in expressed
      human P450 enzymes showed that only CYP3A4 had significant activity in amlodipine
      dehydrogenation. Metabolite profiles and P450 reaction phenotyping data of a
      racemic mixture and S-isomer of amlodipine were very similar. The results from
      this study suggest that CYP3A4, rather than CYP3A5, plays a key role in metabolic
      clearance of amlodipine in humans. 

PMID- 24301609
TI  - Enhanced nicotine metabolism in HIV-1-positive smokers compared with HIV-negative
      smokers: simultaneous determination of nicotine and its four metabolites in their
      plasma using a simple and sensitive electrospray ionization liquid chromatography
      tandem mass spectrometry technique.
AB  - Smoking is approximately three times more prevalent in HIV-1-positive than HIV
      negative individuals in the United States. Nicotine, which is the major
      constituent of tobacco, is rapidly metabolized mainly by cytochrome P450 (CYP2A6)
      to many metabolites. In this study, we developed a simple, fast, and sensitive
      electrospray ionization liquid chromatography-tandem mass spectrometry method
      using a strong cation solid phase extraction, and determined the concentration of
      nicotine and its four major metabolites (cotinine, nornicotine, norcotinine, and
      trans-3'-hydroxycotinine) in the plasma of HIV-1-positive and HIV-negative
      smokers. The multiple reaction monitoring transitions for nicotine, cotinine,
      trans-3'-hydroxycotinine, nornicotine, norcotinine, nicotine-d4, and cotinine-d3
      were selected at mass-to-charge ratios of 163.3/117.1, 177.5/80.3, 193.2/80.1,
      149.5/132.3, 163.4/80.3, 167.3/121.4, and 180.3/101.2, respectively. The lower
      limit of quantitation for nicotine and its metabolites was 0.53 ng/ml, which is
      relatively more sensitive than those previously reported. The concentration of
      nicotine was detected 5-fold lower in HIV-1-positive smokers (7.17 +/- 3.8 ng/ml)
      than that observed in HIV-negative smokers (33.29 +/- 15.4 ng/ml), whereas the
      concentration of the metabolite nornicotine was 3-fold higher in HIV-1-positive
      smokers (6.8 +/- 2.9 ng/ml) than in HIV-negative smokers (2.3 +/- 1.2 ng/ml).
      Although it was statistically nonsignificant, the concentration of the metabolite
      cotinine was also higher in HIV-1-positive smokers (85.6 +/- 60.5 ng/ml) than in
      HIV-negative smokers (74.9 +/- 40.5 ng/ml). In conclusion, a decrease in the
      concentration of nicotine and an increase in the concentration of its metabolites
      in HIV-1-positive smokers compared with HIV-negative smokers support the
      hypothesis that nicotine metabolism is enhanced in HIV-1-positive smokers
      compared with HIV-negative smokers. 

PMID- 24301610
TI  - Optical sinc-shaped Nyquist pulses of exceptional quality.
AB  - Sinc-shaped Nyquist pulses possess a rectangular spectrum, enabling data to be
      encoded in a minimum spectral bandwidth and satisfying by essence the Nyquist
      criterion of zero inter-symbol interference (ISI). This property makes them very
      attractive for communication systems since data transmission rates can be
      maximized while the bandwidth usage is minimized. However, most of the pulse
      shaping methods reported so far have remained rather complex and none has led to
      ideal sinc pulses. Here a method to produce sinc-shaped Nyquist pulses of very
      high quality is proposed based on the direct synthesis of a rectangular-shaped
      and phase-locked frequency comb. The method is highly flexible and can be easily
      integrated in communication systems, potentially offering a substantial increase
      in data transmission rates. Further, the high quality and wide tunability of the
      reported sinc-shaped pulses can also bring benefits to many other fields, such as
      microwave photonics, light storage and all-optical sampling. 

PMID- 24301611
TI  - Percutaneous endoscopic interlaminar discectomy for pediatric lumbar disc
      herniation.
AB  - PURPOSE: Percutaneous endoscopic interlaminar discectomy (PEID) is a widely used
      minimally invasive procedure which shows satisfying outcomes in the adult
      population. However, pediatric lumbar disc herniations (PLDH) occur in growing
      spines and are less related to degeneration, which makes them different from the
      adult disc herniations. This study evaluates the clinical outcomes of PEID in
      treating PLDH. METHODS: A prospect study was done in the period from June 2010 to
      December 2012, which included 29 consecutive pediatric patients with a mean age
      of 16.4 years (range, 13 to 18 years) who underwent PEID for single level lumbar
      disc herniation. The following measuring tools were used: visual analog scale
      (VAS) for back and leg pain, Oswestry Disability Index (ODI), and Macnab
      criteria. RESULTS: There were no severe complications such as dural tear or nerve
      root damage found in our study. The mean follow-up period was 19.7 months. The
      VAS score for leg and back pain decreased dramatically at 1 day postoperatively
      and kept decreasing until the follow-up visit at 3 months postoperatively, when
      it became stable at a low level. ODI kept improving until the follow-up visit at
      6 months postoperatively when it reached a stable low level. Of the patients, 91%
      reported no longer having leg pain and 9% had occasional leg pain at last follow
      up. CONCLUSIONS: PEID shows a satisfying outcome with a minimal rate of
      complications. It has the advantages of minimal traumatization and scar formation
      and is a safe and effective treatment for PLDH.

PMID- 24301612
TI  - Factors associated with self-medication among medicine sellers in urban Vietnam.
AB  - In Vietnam, many medicine sellers serving pharmacies and retail outlets do not
      have adequate professional qualifications, and there has been a limited
      institutional control. The objective of this cross-sectional study was to examine
      the prevalence and determinants of self-medication among medicine sellers in
      Hanoi, Vietnam. Although 96.55% of medicine sellers had relatively serious health
      problems, only 61.21% visited a healthcare facility, though self-medication was
      moderately high (approximately 39%). Adopting Andersen's conceptual model, it was
      identified that medicine sellers who reported higher professional education, had
      low confidence in healthcare services, had not received any professional in
      service during the prior year, had less serious health problems and who perceived
      the current costs of healthcare as too high were more likely to report self
      medication. The findings have public health policy implications for these
      healthcare providers in urban Vietnam and other similar developing countries.

PMID- 24301614
TI  - Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic
      and ion-poor water.
AB  - The contribution of the renin-angiotensin system (RAS) to Na(+) uptake was
      investigated in larval zebrafish (Danio rerio). At 4 days post fertilization
      (dpf), the level of whole-body angiotensin-II (ANG-II) was significantly
      increased after 1- or 3-h exposure to acidic (pH=4.0) or ion-poor water (20-fold
      dilution of Ottawa tapwater), suggesting rapid activation of the RAS. Long-term
      (24 h) treatment of 3 dpf larvae with ANG-I or ANG-II significantly increased
      Na(+) uptake which was accompanied by an increase in mRNA expression of the Na(+)
      Cl(-) cotransporter (zslc12a10.2). Induction of Na(+) uptake by exposure to ANG-I
      was blocked by simultaneously treating larvae with lisinopril (an angiotensin
      converting enzyme inhibitor). Acute (2 h) exposure to acidic water or ion-poor
      water led to significant increase in Na(+) uptake which was partially blocked by
      the ANG-II receptor antagonist, telmisartan. Consistent with these data,
      translational knockdown of renin prevented the stimulation of Na(+) uptake
      following exposure to acidic or ion-poor water. The lack of any effects of
      pharmacological inhibition (using RU486), or knockdown of glucocorticoid
      receptors on the stimulation of Na(+) uptake during acute exposure to acidic or
      ion-poor environments, indicates that the acute effects of RAS occur
      independently of cortisol signaling. The results of this study demonstrate that
      the RAS is involved in Na(+) homeostasis in larval zebrafish. 

PMID- 24301613
TI  - Expression of chemerin and its receptors in rat testes and its action on
      testosterone secretion.
AB  - The novel adipokine chemerin plays a role in the regulation of lipid and
      carbohydrate metabolism, and recent reports of elevated chemerin levels in
      polycystic ovarian syndrome and preeclampsia have pointed to an emerging role of
      chemerin in reproduction. We hypothesised that chemerin, like other adipokines,
      may function to regulate male gonadal steroidogenesis. In this study, we show
      that chemerin and its three receptors chemokine-like receptor 1 (CMKLR1), G
      protein-coupled receptor 1 (GPR1) and chemokine (C-C motif) receptor-like 2 were
      expressed in male reproductive tracts, liver and white adipose tissue. CMKLR1 and
      GPR1 proteins were localised specifically in the Leydig cells of human and rat
      testes by immunohistochemistry. The expression of chemerin and its receptors in
      rat testes was developmentally regulated and highly expressed in Leydig cells. In
      vitro treatment with chemerin suppressed the human chorionic gonadotropin (hCG)
      induced testosterone production from primary Leydig cells, which was accompanied
      by the inhibition of 3beta-hydroxysteroid dehydrogenase gene and protein
      expression. The hCG-activated p44/42 MAPK (Erk1/2) pathway in Leydig cells was
      also inhibited by chemerin cotreatment. Together, these data suggest that
      chemerin is a novel regulator of male gonadal steroidogenesis. 

PMID- 24301615
TI  - Differential regulation of endothelium behavior by progesterone and
      medroxyprogesterone acetate.
AB  - Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly used in
      hormone replacement therapy (HRT). The aim of this research was to study and
      compare the effect of progesterone (Pg) and MPA on the regulation of cellular
      events associated with vascular homeostasis and disease. Platelet adhesion to
      endothelial cells (ECs), nitric oxide (NO) production, and cell migration were
      studied using murine ECs in vitro exposed to the progestins. After 7 min of
      treatment, MPA significantly inhibited NO synthesis with respect to control
      values; meanwhile, Pg markedly increased vasoactive production. In senile ECs,
      the stimulatory action of Pg decreases; meanwhile, MPA maintained its ability to
      inhibit NO synthesis. The presence of RU486 antagonized the action of each
      steroid. When ECs were preincubated with PD98059 (MAPK inhibitor) or
      chelerythrine (protein kinase C (PKC) inhibitor) before Pg or MPA treatment, the
      former totally suppressed the steroid action, but the PKC antagonist did not
      affect NO production. In the presence of a PI3K inhibitor (LY294002), a partial
      reduction in Pg effect and a reversal of MPA action were detected. Using
      indomethacin, the contribution of the cyclooxygenase (COX) pathway was also
      detected. On platelet adhesion assays, Pg inhibited and MPA stimulated platelet
      adhesion to ECs. Under inflammatory conditions, Pg prevented platelet adhesion
      induced by lipopolysaccharide (LPS); meanwhile, MPA potentiated the stimulatory
      action of LPS. Finally, although both steroids enhanced migration of ECs, MPA
      exhibited a greater effect. In conclusion, the data presented in this research
      provide evidence of a differential regulation of vascular function by Pg and MPA.

PMID- 24301616
TI  - How old is old?

PMID- 24301617
TI  - The Buddha and the computer: Meditation in an age of information.
AB  - Information overload is one of the factors behind current alarming statistics on
      stress. Meditation helps the body-mind resist the deleterious effects of the
      information onslaught. Though meditation is well known as a relaxation technique,
      its noetic value is often overlooked. Its benefits extend well beyond superficial
      soothing: it trains attention; it increases pattern recognition; and it
      reconnects us to the whole of our intelligence, enhancing coordination between
      its complementary poles. Meditation is a potent high-touch resource in a high
      tech world. 

PMID- 24301618
TI  - The role of congregations in preventive medicine.
AB  - Congregations are involved in health care, but they don't know it. They have
      seldom examined how they do what they do to encourage healthy ways of living. A
      three-year action research model in the Chicago area incorporates a parish nurse
      on the staff of six large suburban churches. These nurses are essentially health
      educators and personal health counselors. A weekly intensive half-day continuing
      education seminar provides these six nurses with opportunities for interchange
      among themselves and a selected faculty. Perhaps a new specialty within nursing
      is being born-a minister of health to work alongside parish clergy. 

PMID- 24301619
TI  - Adult maturational processes and the facilitating environment.
AB  - The psychoanalytic theory of religion has been seriously limited in its
      development, largely owing to Freud's emphasis on religion's neurotic elements
      and an overemphasis on the infantile origins of religious development. This paper
      offers a conceptual framework and advances the thesis, based on contemporary
      psychoanalytic, developmental theory, that 1) Erikson's concept of epigenesis has
      applicability across the life span; 2) that beyond-the-self identity is
      constituent to human maturation and self-completion; 3) that successful adult
      maturation requires a mirroring-facilitating environment; and 4) that religious
      values, meanings, images, and communities play an essential role-as-elements of
      the facilitating environment of later life. 

PMID- 24301620
TI  - The moment as a factor in emotional well-being.
AB  - The moment is a phenomenon of increasing interest to observers of human
      experience, whether their concern be literature, art, theology, psychology,
      history, or sports. For in the moment an individual's sense of reality is
      heightened and his capacity for choice is intensified. Among the situations where
      our sense of reality can both reflect and produce a significant level of
      emotional well-being are moments where presentness is keenly felt, interpersonal
      relationships, kinetic experiences in sports, the sense of being inspired,
      moments of commitment, highly dramatic presentations of the self, and peak
      experiences. The literature is extensive. 

PMID- 24301621
TI  - Smoking: A Jewish view.
AB  - The issue of smoking and Jewish law is explored. After the dangers from smoking
      are cited, various precedents in Jewish law are presented as the basis for
      confronting the matter of smoking. Arguments are suggested for strictly
      prohibiting smoking. The matter of the effects of smoking on the non-smoker is
      the subject of much research, and the dangers posed to the innocent bystanders
      are an added dimension pointing to the hazards of smoking and therefore
      indicating that it should be prohibited. 

PMID- 24301622
TI  - Natural death and Christian fasting.
AB  - The Christian has a unique resource for responding to the problem of how
      competent adults can exercise responsibly the right to control the last stages of
      their living/dying. Recent natural death legislation offers only a partial
      solution, because it does not specify what counts as life-sustaining procedures
      which may be discontinued if the individual fills out a directive to the
      physician. One of the most troublesome questions continues to be whether the
      withholding or withdrawal of artificial feeding, or indeed natural feeding, is
      ever justifiable. An adaptation of principles included in the Christian idea of
      fasting seems to provide adequate criteria for determining when forgoing
      nourishment by the terminally ill adult is morally justifiable. 

PMID- 24301623
TI  - The Sabbath as dialectic: Implications for mental health.
AB  - Jewish tradition established the Sabbath as a special day. Its observance was
      both part of a religious tradition and an example of psychological health. This
      article explores the values and attitudes that underlie Sabbath observance,
      identifies some of the themes and behaviors most characteristic of these
      observances, and relates these to current mental health practices. 

PMID- 24301624
TI  - Future-time perspective in adolescence: The present of things future revisited.
AB  - Several theorists have suggested that the observed changes in adolescent future
      time perspective are due to the emergence of formal-operations reasoning [e. g.,
      T. J. Cottle and S. Klineberg (1974),The Present of Things Future, Free Press
      Macmillan, New York; P. Fraisse (1963),The Psychology of Time, Harper & Row, New
      York; H. Hartmann (1958),Ego Psychology and the Problem of Adaptation,
      International Universities Press, New York; J. Piaget (1968),Six Psychological
      Studies, Vintage Book, New York]. Using a cross-sectional sample of 60 Caucasian
      adolescents, the present study was designed to examine this hypostatized
      interrelation. Data obtained through individual interviews provide only limited
      support for a cognitive hypothesis. As predicted, older students showed greater
      future extension and the more cognitively advanced students proved better able to
      project a set of events into the distant future. However, neither the older, nor
      the more cognitively advanced, students projected a greater number or a more
      consistent set of future events than did their respective counterparts. Moreover,
      analysis of the types of events projected obtained significance only for grade
      level. The findings are discussed from a contextualist perspective, within which
      consideration is given to the influence of experiential and life-span status
      factors. 

PMID- 24301625
TI  - Introspectiveness and adolescent development.
AB  - This study introduces a measure of introspectiveness for adolescents aged 12-18
      and investigates its association with several aspects of adolescent development.
      Introspectiveness-the tendency to deveote diffuse attention to thoughts and
      feelings about the self-increased during adolescence, and may be stimulated by
      discontinuities associated with adolescent development, other kinds of
      discontinuities, and parental introspectiveness. Also, introspectiveness was
      positively associated with depression, anxiety, and physical symptoms, and may
      help explain the increase in symptom reporting during this developmental period.
      Highly introspective adolescents participated in more artistic activities and
      spent more time alone than those low on introspectiveness. Finally, highly
      introspective college students chose self-oriented academic majors, which may
      have implications for future occupational development. Together these results
      suggest that the concept of introspectiveness may increase our understanding of
      several important aspects of this developmental period. 

PMID- 24301626
TI  - The nuclear family: Correspondence in cognitive and affective reactions to the
      threat of nuclear war among older adolescents and their parents.
AB  - In order to assess the relationship between family members' cognitive and
      affective responses to nuclear war issues, 317 college students and their parents
      (n=559) independently completed a multifaceted questionnaire that included items
      concerning personal reactions, predictions, opinions, and attitudes about nuclear
      war. Results revealed a negligible relationship between the responses of college
      students and their parents, although the level of concordance between mothers and
      fathers was somewhat greater. Moreover, parents and students were relatively poor
      at predicting each others' nuclear threat attitudes, and the strength with which
      an attitude was endorsed did not enhance its predictability. Results are
      discussed with regard to heterogeneity in attitudinal and affective reactions
      within families, and with regard to the idea that infrequent communication
      concerning nuclear war issues may be occurring. 

PMID- 24301627
TI  - Ego development and moral development in relation to age and grade level during
      adolescence.
AB  - The relation between Loevinger's measure of ego development and moral development
      as indexed by Rest's Defining Issues Test was examined in a sample of 517
      adolescents between 12 and 21 years of age. Major increases in moral capacity
      were found at the Conformist and Conscientious levels of ego development. Low
      positive correlations between ego level and moral capacity were reported for
      young adolescents but not for older ones. The development indices of age and
      grade were compared. Both ego and moral development seemed more closely related
      to grade level than to age. Socioeconomic status predicted acceleration in ego
      development at the rate of one half an ego level over middle to late adolescence.
      This effect persisted at university. Students of higher socioeconomic background
      attained developmental levels one to two years before their contemporaries of low
      socioeconomic status. Sex differences in ego development were in favor of
      females. 

PMID- 24301628
TI  - Sex differences in the Beck Depression inventory scores of adolescents.
AB  - The purpose of the present study is to evaluate the potential differences between
      male and female adolescents in their performance on the Beck Depression Inventory
      (BDI) as a function of demographic variables and variables related to their
      living conditions. Three hundred and twelve adolescents between the ages of 13
      and 17 completed the BDI and a questionnaire dealing with the variables mentioned
      above. All adolescents were from the Western Quebec area and were registered at
      De l'Ile High School (Hull) or at L'Erabliere High School (Gatineau). Differences
      in the BDI scores were observed between female and male adolescents, with females
      scoring significantly higher than males. However, none of the variables included
      in the questionnaire had a differential effect on the BDI scores of either male
      or female adolescents. The results are discussed in light of their relationship
      with some adjustment factors in adolescence. 

PMID- 24301629
TI  - Drinking adolescents on the roads.
AB  - A social-learning model [R. C. Akers, M. D. Krohn, L. Lanza-Koduce, and M.
      Radosevich (1979), "Social Learning and Deviant Behavior: A Specific Test of a
      General Theory,"American Sociology Review, 44: 636-655] was tested for its
      ability to explain why adolescents drive under the influence of alcohol and ride
      with drinking drivers. Data were gathered from a survey of 1,082 high school
      students. Findings indicate that all five subsets of the model are significant
      determinants of adolescent driving under the influence and riding with drinking
      drivers. The study demonstrates that if adolescent drinking and driving is to be
      prevented, careful attention must be paid to ways that it is learned and
      maintained. 

PMID- 24301630
TI  - Erratum.

PMID- 24301631
TI  - Bandgap engineering through nanoporosity.
AB  - Considering 105 ZnO polymorphs we use many body GW and density functional based
      calculations to probe how the band gap is affected by nanoporosity. Within a
      reasonable range of energetic stability, we predict that nanoporosity can induce
      band gap increases of up to ~1.5 eV relative to wurtzite ZnO. Our results further
      imply that structural stability and band gap increase are fundamentally linked to
      pore system dimensionality. We suggest that nanoporosity could be employed as a
      general band gap engineering method for morphologically and electronically
      tailored functional materials.

PMID- 24301632
TI  - Inhibition of Photosystem 2 primary photochemistry by photogenerated protons.
AB  - Photosystem 2 photochemical efficiency, measured as the rate of Qa reduction, was
      observed to be inhibited by preillumination with single turnover flashes, whilst
      Fo and Fm were not affected. Such inhibition was reversed by the uncoupler
      nigericin or by incubating the thylakoids in the dark for ca. 2 min after the
      preillumination. The presence of ATP in micromolar concentrations increased the
      time of dark recovery from the inhibition. The inhibition of fluorescence rise
      was not changed when 70% of the excitation energy available in the antenna was
      quenched by dinitrobenzene. Quantitative analysis of the observed fluorescence
      induction indicates that this phenomenon is due to the inhibition of the
      photochemical reaction itself. Uncouplers such NH4Cl were unable to reverse the
      inhibition and only a few flashes of saturating intensity (10 or less) were
      required for the onset of it. This suggests that protons localised in domains
      rather than a pH gradient between the thylakoid lumen bulk solution and the
      external one are involved in this regulation of PS 2 efficiency. 

PMID- 24301633
TI  - Down regulation of photosynthesis in Artabotrys hexapetatus by high light.
AB  - Using variable to maximum fluorescence (Fv/Fm) as the criterion, the down
      regulation of photosynthesis by high light stress was characterized in the
      detached leaves of Artabotrys hexapetatus. The decrease in Fv/Fm was corelated
      with the decrease in oxygen evolution by thylakoids isolated from high light
      exposed leaves. The decrease in Fv/Fm was linear with increasing time of exposure
      to high light. A comparison of recovery measured as Fv/Fm, in low light versus
      dark, revealed that the recovery in darkness was as significant as in low light.
      Since the relaxation of fluorescence was a rapid response after exposure to high
      light and the fact that the recovery occurs in total darkness, it is concluded
      that photoinhibition and down regulation of photosynthesis by high light are
      independent events. 

PMID- 24301634
TI  - Superoxide radicals are not the main promoters of acceptor-side-induced
      photoinhibitory damage in spinach thylakoids.
AB  - Superoxide anion radical formation was studied with isolated spinach thylakoid
      membranes and oxygen evolving Photosystem II sub-thylakoid preparations using the
      reaction between superoxide and Tiron (1,2-dihydroxybenzene-3,5-disulphonate)
      which results in the formation of stable, EPR detectable Tiron radicals.We found
      that superoxide was produced by illuminated thylakoids but not by Photosystem II
      preparations. The amount of the radicals was about 70% greater under
      photoinhibitory conditions than under moderate light intensity. Superoxide
      production was inhibited by DCMU and enhanced 4-5 times by methyl viologen. These
      observations suggest that the superoxide in illuminated thylakoids is from the
      Mehler reaction occurring in Photosystem I, and its formation is not primarily
      due to electron transport modifications brought about by
      photoinhibition.Artificial generation of superoxide from riboflavin accelerated
      slightly the photoinduced degradation of the Photosystem II reaction centre
      protein D1 but did not accelerate the loss of oxygen evolution supported by a
      Photosystem II electron acceptor. However, analysis of the protein breakdown
      products demonstrated that this added superoxide did not increase the amount of
      fragments brought about by photoinhibition but introduced an additional pathway
      of damage.On the basis of the above observations we propose that superoxide
      redicals are not the main promoters of acceptor-side-induced photoinhibition of
      Photosystem II. 

PMID- 24301635
TI  - Photosynthetic acclimation and photosynthate partitioning in soybean leaves in
      response to carbon dioxide enrichment.
AB  - Photosynthetic rates and photosynthate partitioning were studied in three-week
      old soybean [Glycine max (L.) Merr. cv. Williams] plants exposed to either
      ambient (35 Pa) or elevated (70 Pa) CO2 in controlled environment chambers.
      Ambient CO2-grown plants also were given a single 24 h treatment with 70 Pa CO2 1
      d prior to sampling. Photosynthetic rates of ambient CO2-grown plants initially
      increased 36% when the measurement CO2 was doubled from 35 to 70 Pa.
      Photosynthetic rates of the third trifoliolate leaf, both after 1 and 21 d of
      elevated CO2 treatment, were 30 to 45% below those of ambient CO2-grown plants
      when measured at 35 Pa CO2. These reduced photosynthetic rates were not due to
      increased stomatal resistance and were observed for 2 to 8 h after plants given 1
      d of CO2 enrichment were returned to ambient CO2. Initial and total ribulose 1,5
      bisphosphate carboxylase/oxygenase (Rubisco) activities, percent activation,
      Rubisco protein, soluble protein and leaf chlorophyll content were similar in all
      CO2 treatments. Quantum yields of photosynthesis, determined at limiting
      irradiances and at 35 Pa CO2, were 0.049+/-0.003 and 0.038+/-0.005 mol CO2 fixed
      per mol quanta for ambient and elevated CO2-grown plants, respectively (p<0.05).
      Leaf starch and sucrose levels were greater in plants grown at 70 than at 35 Pa
      CO2. Starch accumulation rates during the day were greater in ambient CO2-grown
      plants than in plants exposed to elevated CO2 for either 1 or 21 d. However, the
      percentage of C partitioned to starch relative to total C fixed was unaffected by
      1 d of CO2 enrichment. The above results showed that both photosynthetic and
      starch accumulation rates of soybean leaflets measured at 35 Pa CO2 were
      temporarily reduced after 1 and 21 d of CO2 enrichment. The biochemical mechanism
      affecting these responses was not identified. 

PMID- 24301636
TI  - Functional activities of monomeric and dimeric forms of the chloroplast
      cytochrome b6f complex.
AB  - A monomeric form of the isolated cytochrome b6f complex from spinach chloroplast
      membranes has been isolated after treatment of the dimeric complex with varying
      concentrations of Triton X-100. The two forms of the complex are similar as
      regards electron transfer components and subunit composition. In contrast to a
      previous report (Huang et al. (1994) Biochemistry 33: 4401-4409) both the monomer
      and dimer are enzymatically active. However, after incorporation of the
      respective complexes into phospholipid vesicles, only the dimeric form of the
      cytochrome complex shows uncoupler sensitive electron transport, an indication of
      coupling of electron transport to proton translocation. The absence of this
      activity with the monomeric form of the cytochrome complex may be related to an
      inhibition by added lipids. 

PMID- 24301637
TI  - Aggregation of 8,12-diethyl farnesyl bacteriochlorophyll c at low temperature.
AB  - The effect of temperature on the aggregation of 3(l)R-8,12-diethyl farnesyl
      bacteriochlorophyll c in a mixture of n-pentane and methylcyclohexane (1/1, v/v)
      was studied by means of absorption, circular dichroism and fluorescence
      spectroscopy. At room temperature essentially only two aggregate species,
      absorbing at 702 nm (A-702) and 719 nm (A-719), were present. Upon cooling to 219
      K, A-702 was quantitatively converted to A-719. Further lowering of the
      temperature led to the stepwise formation of larger aggregates by the conversion
      of A-719 to aggregate species absorbing at 743 nm (A-743) and 755 nm (A-755). All
      absorption changes were reversible. A-719 was highly fluorescent (maximum at 192
      K: 744 nm), while A-743 and especially A-755 were weakly fluorescent. Below 130 K
      the mixture solidified, and no major changes in the absorption spectrum were
      observed upon further cooling. At 45 K, however, a relatively strong emission at
      775 nm was observed. Below 200 K, the absorption, fluorescence and circular
      dichroism spectra resembled that of the chlorosome. These results open up the
      possibility to study higher aggregates of BChl c as models for the chlorosome by
      various methods at low temperature, thus avoiding interference by thermal
      processes. 

PMID- 24301638
TI  - Form II of D1 is important during transition from standard to high light
      intensity in Synechococcus sp. strain PCC 7942.
AB  - In Synechococcus sp. strain PCC 7942 the D1 protein of Photosystem II is encoded
      by a multigene family; psbAI encodes Form I of D1 whereas both psbAII and psbAIII
      encode Form II. The psbA genes are differentially regulated in response to
      changes in light intensity, such that psbAI expression and Form I predominate at
      standard light intensity, whereas psbAII and psbAIII are induced at high light
      intensity, causing insertion of Form II into the thylakoids. The present study
      addressed whether high-light induced Form II is important for Synechococcus cells
      during adaptation to high light intensity. Wild-type Synechococcus, and mutants
      which produce only Form I (R2S2C3) or only Form II (R2K1), were co-cultured at
      standard light (130 MUE . m(-2) . s(-1)) and then shifted to high light (750
      MUE.m(-2).s(-1)). Measurement of the proportion of each cell type at various time
      intervals revealed that the growth of R2S2C3, which has psbAII and psbAIII
      inactive, and thus lacks Form II, is transiently impaired upon shift to high
      light. Both mutants R2S2C3 and R2K1 maintained normal levels of psbA messages and
      D1 protein under standard and high light through an unknown mechanism that
      compensates for the inactive psbA genes. Thus, the impairment of R2S2C3 at high
      light is not due to a deficiency of D1 protein, but results from lack of Form II.
      We discounted the influence of possible secondary mutations by re-creating the
      psbA-inactivated mutants and testing the newly isolated strains. We conclude that
      Form II of D1 is intrinsically important for Synechococcus cells during a
      critical transition period after exposure to high light intensities. 

PMID- 24301639
TI  - Light-regulated pigment interconversion in pheophytin/chlorophyll-containing
      complexes formed during plant leaves greening.
AB  - Upon illumination of etiolated maize leaves the photoconversion of
      protochlorophyllide Pchlide 655/650 into chlorophyllide Chlide 684/676 was
      observed. It was shown that chlorophyllide Chlide 684/676 in the dark is
      transformed into pheophytin Pheo 679/675 and chlorophyll Chl 671/668 by means of
      two parallel reactions, occurring at room temperature: Chlide 684/676. The formed
      pheophytin Pheo 679/675 was unstable and in the dark was transformed into
      chlorophyll Chl 671/668 in a few seconds: Pheo 679/675 -> Chl 671/668. The last
      reaction is reversed by the light: Chl/668 Pheo 679/675. Thus, on the whole in
      the greening etiolated leaves this process occurs according to the following
      scheme:The observed light-regulated interconversion of Mg-containing and Mg-free
      chlorophyll analogs is activated by ATP and inhibited by AMP. 

PMID- 24301640
TI  - Inhibition of photosynthetic oxygen evolution by protonophoric uncouplers.
AB  - The protonophoric uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP),
      2,3,4,5,6-pentachlorophenol (PCP) and 4,5,6,7-tetrachloro-2
      trifluoromethylbenzimidazole (TTFB) inhibited the Hill reaction with K3[Fe(CN)6]
      (but not with SiMo) in chloroplast and cyanobacterial membranes (the I50 values
      were approx. 1-2, 4-6 and 0.04-0.10 MUM, respectively). The inhibition is due to
      oxidation of the uncouplers on the Photosystem II donor side (ADRY effect) and
      their subsequent reduction on the acceptor side, ie. to the formation of a cyclic
      electron transfer chain around Photosystem II involving the uncouplers as redox
      carriers. The relative amplitude of nanosecond chlorophyll fluorescence in
      chloroplasts was increased by DCMU or HQNO and did not change upon addition of
      uncouplers, DBMIB or DNP-INT; the HQNO effect was not removed by the uncouplers.
      The uncouplers did not inhibit the electron transfer from reduced TMPD or
      duroquinol to methylviologen which is driven by Photosystem I. These data show
      that CCCP, PCP and TTFB oxidized on the Photosystem II donor side are reduced by
      the membrane pool of plastoquinone (Qp) which is also the electron donor for K3
      [Fe(CN)6] in the Hill reaction as deduced from the data obtained in the presence
      of inhibitors. Inhibition of the Hill reaction by the uncouplers was maximum at
      the pH values corresponding to the pK of these compounds. It is suggested that
      the tested uncouplers serve as proton donors, and not merely as electron donors
      on the oxidizing side of Photosystem II. 

PMID- 24301641
TI  - Calibration of the Minolta SPAD-502 leaf chlorophyll meter.
AB  - Use of leaf meters to provide an instantaneous assessment of leaf chlorophyll has
      become common, but calibration of meter output into direct units of leaf
      chlorophyll concentration has been difficult and an understanding of the
      relationship between these two parameters has remained elusive. We examined the
      correlation of soybean (Glycine max) and maize (Zea mays L.) leaf chlorophyll
      concentration, as measured by organic extraction and spectrophotometric analysis,
      with output (M) of the Minolta SPAD-502 leaf chlorophyll meter. The relationship
      is non-linear and can be described by the equation chlorophyll (MUmol m(
      2))=10((M0.265)), r (2)=0.94. Use of such an exponential equation is
      theoretically justified and forces a more appropriate fit to a limited data set
      than polynomial equations. The exact relationship will vary from meter to meter,
      but will be similar and can be readily determined by empirical methods. The
      ability to rapidly determine leaf chlorophyll concentrations by use of the
      calibration method reported herein should be useful in studies on photosynthesis
      and crop physiology. 

PMID- 24301643
TI  - Corrigendum : volume 45: 111-119, 1995.

PMID- 24301642
TI  - A serendipic legacy: Erwin Esmarch's isolation of the first photosynthetic
      bacterium in pure culture.
AB  - During the 1880's, Erwin von Esmarch was a junior associate ('Assistent') of
      Robert Koch studying bacteria of medical significance. In 1887, he isolated the
      first example of spiral-shaped bacteria in pure culture, from the dry residue of
      a dead mouse that he had suspended sometime earlier in Berlin tap-water. Under
      certain conditions, colonies of the organism were the color of red wine, and this
      led Esmarch to name the bacterium Spirillum rubrum. Twenty years later, Hans
      Molisch demonstrated that S. rubrum, an apparent heterotroph, was in fact a non
      oxygenic purple photosynthetic bacterium, and it was renamed Rhodospirillum
      rubrum. Esmarch was a careful investigator and his classic paper of 1887 details
      the serendipitous isolation and general characteristics of the first pure culture
      of an anoxyphototroph, which later played a prominent role as an experimental
      system for study of basic aspects of bacterial photosynthesis. This report
      includes an English translation of his original paper (in German), a commentary
      on the historical significance of 'Esmarch's spirillum', and a summary of
      Esmarch's career. 

PMID- 24301644
TI  - The end-of-life experience: modifiable predictors of caregivers' bereavement
      adjustment.
AB  - BACKGROUND: The objective of the current study was to determine the best set of
      predictors of psychological disorders, regrets, health-related quality of life,
      and mental health function among bereaved caregivers of patients with cancer,
      thereby identifying promising targets for interventions to improve bereavement
      adjustment. METHODS: Coping with Cancer is a longitudinal study of patients with
      advanced cancer and their informal caregivers who were enrolled from 2002 to
      2008. The main outcome measure was bereavement adjustment of 245 caregivers (eg,
      depression, anxiety, and regrets) 6 months after the loss of the patient. The
      Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental
      Disorders determined whether caregivers met the criteria for major depressive
      disorder or an anxiety disorder. Changes in health-related quality of life and
      mental health function from baseline to after the patient's death were assessed
      with the Medical Outcomes Study Short Form (SF-36). RESULTS: Greater than 50% of
      the caregivers reported regret about the cancer patient's end-of-life care;
      better patient quality of death (adjusted odds ratio, 0.77; 95% confidence
      interval, 0.67-0.88) reduced the risk of bereavement regret. The incidence of
      major depressive disorder or anxiety among the bereaved caregivers was 12.6% and
      was less likely for caregivers with better mental health before the loss of the
      patient (adjusted odds ratio, 0.03; 95% confidence interval, 0.004-0.25). Better
      patient quality of death also predicted improved caregiver health-related quality
      of life (adjusted standardized beta, .28; P < .001). The completion of a do-not
      resuscitate order was found to be predictive of improved mental health from
      before the death of the patient to after the death (adjusted standardized beta,
      .29; P < .001). CONCLUSIONS: Reducing caregiver distress, encouraging advance
      care planning by patients, and improving patients' quality of death appear to be
      promising targets of interventions to improve caregiver bereavement adjustment.

PMID- 24301645
TI  - Locomotor hyperactivity in 14-3-3zeta KO mice is associated with dopamine
      transporter dysfunction.
AB  - Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions
      that are tightly linked to catecholamine exocytosis and receptor interactions on
      pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily
      achieved through reuptake of extracellular DA by the DA transporter (DAT) on
      presynaptic neurons. Aberrant regulation of DA signalling, and in particular
      hyperactivation, has been proposed as a key insult in the presentation of
      schizophrenia and related neuropsychiatric disorders. We recently identified 14-3
      3zeta as an essential component of neurodevelopment and a central risk factor in
      the schizophrenia protein interaction network. Our analysis of 14-3-3zeta
      deficient mice now shows that baseline hyperactivity of knockout (KO) mice is
      rescued by the antipsychotic drug clozapine. 14-3-3zeta KO mice displayed
      enhanced locomotor hyperactivity induced by the DA releaser amphetamine.
      Consistent with 14-3-3zeta having a role in DA signalling, we found increased
      levels of DA in the striatum of 14-3-3zeta KO mice. Although 14-3-3zeta is
      proposed to modulate activity of the rate-limiting DA biosynthesis enzyme,
      tyrosine hydroxylase (TH), we were unable to identify any differences in total TH
      levels, TH localization or TH activation in 14-3-3zeta KO mice. Rather, our
      analysis identified significantly reduced levels of DAT in the absence of notable
      differences in RNA or protein levels of DA receptors D1-D5. Providing insight
      into the mechanisms by which 14-3-3zeta controls DAT stability, we found a
      physical association between 14-3-3zeta and DAT by co-immunoprecipitation. Taken
      together, our results identify a novel role for 14-3-3zeta in DA
      neurotransmission and provide support to the hyperdopaminergic basis of
      pathologies associated with schizophrenia and related disorders. 

PMID- 24301646
TI  - Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal
      cognitive dysfunction.
AB  - Recent genetic studies have linked mental illness to alterations in disrupted in
      schizophrenia 1 (DISC1), a multifunctional scaffolding protein that regulates
      cyclic adenosine monophosphate (cAMP) signaling via interactions with
      phosphodiesterase 4 (PDE4). High levels of cAMP during stress exposure impair
      function of the prefrontal cortex (PFC), a region gravely afflicted in mental
      illness. As stress can aggravate mental illness, genetic insults to DISC1 may
      worsen symptoms by increasing cAMP levels. The current study examined whether
      viral knockdown (KD) of the Disc1 gene in rat PFC increases susceptibility to
      stress-induced PFC dysfunction. Rats were trained in a spatial working memory
      task before receiving infusions of (a) an active viral construct that knocked
      down Disc1 in PFC (DISC1 KD group), (b) a 'scrambled' construct that had no
      effect on Disc1 (Scrambled group), or (c) an active construct that reduced DISC1
      expression dorsal to PFC (Anatomical Control group). Data were compared with an
      unoperated Control group. Cognitive performance was assessed following mild
      restraint stress that had no effect on normal animals. DISC1 KD rats were
      impaired by 1  h restraint stress, whereas Scrambled, Control, and Anatomical
      Control groups were unaffected. Thus, knocking down Disc1 in PFC reduced the
      threshold for stress-induced cognitive dysfunction, possibly through disinhibited
      cAMP signaling at neuronal network synapses. These findings may explain why
      patients with DISC1 mutations may be especially vulnerable to the effects of
      stress. 

PMID- 24301647
TI  - Neurodevelopmental disorders: mechanisms and boundary definitions from genomes,
      interactomes and proteomes.
AB  - Neurodevelopmental disorders such as intellectual disability, autism spectrum
      disorder and schizophrenia lack precise boundaries in their clinical definitions,
      epidemiology, genetics and protein-protein interactomes. This calls into question
      the appropriateness of current categorical disease concepts. Recently, there has
      been a rising tide to reformulate neurodevelopmental nosological entities from
      biology upward. To facilitate this developing trend, we propose that
      identification of unique proteomic signatures that can be strongly associated
      with patient's risk alleles and proteome-interactome-guided exploration of
      patient genomes could define biological mechanisms necessary to reformulate
      disorder definitions. 

PMID- 24301648
TI  - Loss of serum IGF-I input to the brain as an early biomarker of disease onset in
      Alzheimer mice.
AB  - Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes
      clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD)
      brains. Both patients and mouse models of AD show decreased level of circulating
      IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma
      IGF-I. Importantly, in presymptomatic AD mice this reduction is already
      manifested as a decreased brain input of serum IGF-I in response to environmental
      enrichment. To explore a potential diagnostic use of this early loss of IGF-I
      input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice.
      Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD
      mice showed blunted ECG responses. Because nonhuman primates showed identically
      enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss
      of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD
      patients. 

PMID- 24301649
TI  - Knockdown of BNST GluN2B-containing NMDA receptors mimics the actions of ketamine
      on novelty-induced hypophagia.
AB  - Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor
      antagonist ketamine has been demonstrated to elicit long-lasting antidepressant
      effects in humans with depression, as well as in rodent models of depression.
      Although pharmacological studies have implicated the GluN2B subunit of the NMDA
      receptor in these effects, drugs targeting this subunit have off-target actions,
      and systemic administration of these compounds does not allow for delineation of
      specific brain regions involved. In this study, we assessed the role of GluN2B in
      the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia
      (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist
      Ro25-6981, decreased the latency to consume food in a novel environment in a
      version of the NIH test. We then hypothesized that GluN2B-containing receptors
      within the BNST may be a target of systemic ketamine and contribute to behavioral
      effects. Through the combination of a GluN2B-floxed mouse line and stereotaxic
      delivery of lentiviral Cre recombinase, we found that targeted knockdown of this
      subunit within the BNST mimicked the reduction in affective behavior observed
      with systemic ketamine or Ro25-6981 in the NIH test. These data suggest a role
      for GluN2B-containing NMDARs within the BNST in the affective effects of systemic
      ketamine. 

PMID- 24301652
TI  - 1,8-Cineole (Eucalyptol), a mosquito feeding and ovipositional repellent from
      volatile oil ofHemizonia fitchii (Asteraceae).
AB  - The mosquito feeding and ovipositional repellency of the major monoterpenoid
      present in the volatile oil ofHemizonia fitchii (Asteraceae), i.e., 1,8-cineole,
      was investigated. Although 1,8-cineole did not exhibit any significant mosquito
      larvicidal activity, it was moderately effective as a feeding repellent and
      highly effective as an ovipositional repellent against adultAedes aegypti (yellow
      fever mosquito). The ovipositional repellency of 1,8-cineole, coupled with the
      presence of severalHemizonia chromenes previously shown to possess mosquito
      larvicidal activity, may therefore account in large part for the observed
      suppression of local mosquito populations which was associated withH. fitchii
      plants in northern California. 

PMID- 24301650
TI  - Latrepirdine: molecular mechanisms underlying potential therapeutic roles in
      Alzheimer's and other neurodegenerative diseases.
AB  - Latrepirdine (Dimebon(TM)) was originally marketed as a non-selective
      antihistamine in Russia. It was repurposed as an effective treatment for patients
      suffering from Alzheimer's disease (AD) and Huntington's disease (HD) following
      preliminary reports showing its neuroprotective functions and ability to enhance
      cognition in AD and HD models. However, latrepirdine failed to show efficacy in
      phase III trials in AD and HD patients following encouraging phase II trials. The
      failure of latrepirdine in the clinical trials has highlighted the importance of
      understanding the precise mechanism underlying its cognitive benefits in
      neurodegenerative diseases before clinical evaluation. Latrepirdine has shown to
      affect a number of cellular functions including multireceptor activity,
      mitochondrial function, calcium influx and intracellular catabolic pathways;
      however, it is unclear how these properties contribute to its clinical benefits.
      Here, we review the studies investigating latrepirdine in cellular and animal
      models to provide a complete evaluation of its mechanisms of action in the
      central nervous system. In addition, we review recent studies that demonstrate
      neuroprotective functions for latrepirdine-related class of molecules including
      the beta-carbolines and aminopropyl carbazoles in AD, Parkinson's disease and
      amyotrophic lateral sclerosis models. Assessment of their neuroprotective effects
      and underlying biological functions presents obvious value for developing
      structural analogues of latrepirdine for dementia treatment. 

PMID- 24301651
TI  - FLAP pharmacological blockade modulates metabolism of endogenous tau in vivo .
AB  - FLAP (5-lipoxygenase-activating protein) is a protein widely distributed within
      the central nervous system whose function is to regulate the activation of the 5
      Lipoxygenase enzyme. Although previous works show that pharmacological blockade
      of FLAP improve the amyloidotic phenotype of the Tg2576, its contribution to tau
      pathology remains to be investigated. In the present paper, we studied the effect
      of FLAP pharmacological inhibition on the metabolism of endogenous tau in these
      mice. Total tau levels in the brains of mice receiving MK-591, a selective and
      specific FLAP inhibitor, were not changed when compared with controls. By
      contrast, treated animals had a significant reduction of tau phosphorylation at
      specific sites: Ser396; Ser396/Ser404; and Thr 231/Ser 235. This reduction was
      associated with a significant decrease in the activity of glycogen synthase
      kinase-3 beta, but not other kinases. In addition, MK-591-treated mice had a
      significant increase in the post-synaptic density protein-95 and the dendritic
      protein microtubule-associated protein 2. These data establish a novel functional
      role for FLAP in the metabolism of tau, and together with its known Abeta
      modulatory effect they suggest that its pharmacological inhibition could
      represent a novel therapeutic opportunity for Alzheimer's disease. 

PMID- 24301653
TI  - Interactions of pheromone component odor plumes of western pine beetle.
AB  - The relationships between catch ofD. brevicomis LeC. at sources of the
      synergistic pheromone components,exo-brevicomin (E) and frontalin (F), and
      increasing distance of separation of sources were investigated in the forest. The
      two components were each released with the host monoterpene, myrcene (M), in trap
      pairs. The traps of each pair were spaced apart at various distances (0-16 m) in
      either horizontal or vertical lines that were perpendicular to the mean wind
      direction. Both sexes were most strongly attracted when the two components were
      released from the same source, and increasing distance of separation between
      components caused exponential decreases in trap catch for all trap
      configurations. Males were significantly more attracted to traps with E, M alone
      than to corresponding traps with F, M alone, while females exhibited a preference
      for F, M. The theoretical relationships and properties of two coalescing plumes
      of individual components and their intersecting "active space" are presented and
      discussed. It is proposed that "confusion" or "communication disruption"
      techniques for insect control may be more successful if components are released
      individually from many points rather than released similarly in blends. 

PMID- 24301654
TI  - Determination of chirality in 5-hydroxy-4-methyl-3-heptanone, the aggregation
      pheromone ofSitophilus oryzae (L.) andS. zeamais Motschulsky.
AB  - The chirality of the pheromone of the rice weevil,Sitophilus oryzae (L.), and the
      maize weevil,S. zeamais (Motschulsky), 5-hydroxy-4-methyl-3-heptanone, was
      determined using an acetyl lactate derivatization procedure. Maize weevils were
      shown to produce >98% 4S,5R. Determination was more difficult with rice weevils
      due to a smaller quantity of insect extract, but they were shown to produce at
      least 92% 4S, 5R.The attractancy of the four synthetic stereoisomers of 5-hydroxy
      4-methyl-3-heptanone was tested using rice and maize weevils. As expected, both
      species were most strongly attracted to the 4S, 5R enantiomer. Maize weevils also
      showed low but significant responses (P < 0.05) to both 4R, 5R and 4S,5S. Rice
      weevils showed a highly significant (P < 0.01) response to 4R, 5S, although it
      was only about one third the response to 4S, 5R. Thus, (4S,5R)-5-hydroxy-4-methyl
      3-heptanone is clearly the major component of the pheromone of bothS. zeamais
      andS. oryzae. 

PMID- 24301655
TI  - Males follow females during fissioning of a group of northern muriquis.
AB  - Although well documented in matrilocal primate species, group fission is still a
      poorly known phenomenon among patrilocal primates. In this paper we describe in
      detail a group fission event in the population of northern muriquis at the
      Reserva Particular do Patrimonio Natural-Feliciano Miguel Abdala in Caratinga,
      Minas Gerais, Brazil, using Social Network Analyses (SNA). Data on association
      patterns were collected during systematic observations from May 2002 to September
      2005, and analyzed for dry (from May to October) and rainy seasons (from November
      to April). The fission process started with subgroup formation in the rainy
      season 2002-2003, and was completed by the dry season of 2003. By the dry season
      2003, the parent group (Jao) had fissioned to form a second mixed-sex group
      (Nadir) while a subgroup of males (MU) moved between the parent group and the
      newly established group. Before the Jao group fission started (dry season 2002)
      and during its initial phases (rainy season 2002-2003), females that ultimately
      composed the daughter group (Nadir) were the most peripheral in the association
      network. In the rainy season 2002-2003, the median monthly (N=6) operational sex
      ratio (OSR) of Jao group was 2.81. However, once Jao females initiated the
      fissioning process to establish the Nadir group, the OSR was more favorable to
      males in the Nadir group than in the Jao group. Our results suggest that males
      followed the females to escape an unfavorable OSR in their natal group.

PMID- 24301656
TI  - Minor units take a growing share of emergency department attendances.

PMID- 24301657
TI  - IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis.
AB  - Breakdown of the epithelial barrier because of toxins or other insults leads to
      severe colitis. Interleukin-10 (IL-10) is a critical regulator of this, yet its
      cellular targets and mechanisms of action are not resolved. We address this here.
      Mice with a macrophage-selective deletion of IL-10Ralpha (IL-10Ralpha(Mdel))
      developed markedly enhanced dextran sodium sulfate (DSS)-induced colitis that did
      not significantly differ from disease in IL-10(-/-) or IL-10Ralpha(-/-) mice; no
      impact of IL-10Ralpha deficiency in other lineages was observed. IL
      10Ralpha(Mdel) colitis was associated with increased mucosal barrier disruption
      in the setting of intact epithelial regeneration. Lamina propria macrophages
      (LPMphis) did not show numerical or phenotypic differences from controls, or a
      competitive advantage over wild-type cells. Proinflammatory cytokine production,
      and particularly tumor necrosis factor-alpha (TNF-alpha), was increased, although
      TNF-alpha neutralization failed to reveal a defining role for this cytokine in
      the aggravated disease. Rather, IL-10Ralpha(Mdel) LPMphis produced substantially
      greater levels of nitric oxide (NO) and reactive oxygen species (ROS) than
      controls. Inhibition of these had modest effects in wild-type mice, although they
      dramatically reduced colitis severity in IL-10Ralpha(Mdel) mice, and largely
      eliminated the differential effect of DSS in them. Therefore, the palliative
      actions of IL-10 in DSS-induced colitis predominantly results from its macrophage
      specific effects. Downregulation of NO and ROS production are central to the
      protective actions of IL-10. 

PMID- 24301660
TI  - Reflections on current research and future challenges in cultural psychiatry.

PMID- 24301658
TI  - Antigen-specific expansion of human regulatory T cells as a major tolerance
      mechanism against mucosal fungi.
AB  - Foxp3(+) regulatory T cells (Treg) have a central role for keeping the balance
      between pro- and anti-inflammatory immune responses against chronically
      encountered antigens at mucosal sites. However, their antigen specificity
      especially in humans is largely unknown. Here we used a sensitive enrichment
      technology for antigen-reactive T cells to directly compare the conventional vs.
      regulatory CD4(+) T-cell response directed against two ubiquitous mucosal fungi,
      Aspergillus fumigatus and Candida albicans. In healthy humans, fungus-specific
      CD4(+)CD25(+)CD127(-)Foxp3(+) Treg are strongly expanded in peripheral blood and
      possess phenotypic, epigenetic and functional features of thymus-derived Treg.
      Intriguingly, for A. fumigatus, the strong Treg response contrasts with minimal
      conventional T-cell memory, indicating selective Treg expansion as an effective
      mechanism to prevent inappropriate immune activation in healthy individuals. By
      contrast, in subjects with A. fumigatus allergies, specific Th2 cells were
      strongly expanded despite the presence of specific Treg. Taken together, we
      demonstrate a largely expanded Treg population specific for mucosal fungi as part
      of the physiological human T-cell repertoire and identify a unique capacity of A.
      fumigatus to selectively generate Treg responses as a potentially important
      mechanism for the prevention of allergic reactions. 

PMID- 24301659
TI  - Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance
      in IBD.
AB  - A defective induction of epithelial autophagy may have a role in the pathogenesis
      of inflammatory bowel diseases. This process is regulated mainly by extracellular
      factors such as nutrients and growth factors and is highly induced by diverse
      situations of stress. We hypothesized that epithelial autophagy is regulated by
      the immune response that in turn is modulated by local hypoxia and inflammatory
      signals present in the inflamed mucosa. Our results reveal that HIF-1alpha and
      Wnt1 were co-localized with CD68 in cells of the mucosa of IBD patients. We have
      observed increased protein levels of beta-catenin, phosphorylated mTOR, and p62
      and decreased expression of LC3II in colonic epithelial crypts from damaged
      mucosa in which beta-catenin positively correlated with phosphorylated mTOR and
      negatively correlated with autophagic protein markers. In cultured macrophages,
      HIF-1 mediated the increase in Wnt1 expression induced by hypoxia, which enhanced
      protein levels of beta-catenin, activated mTOR, and decreased autophagy in
      epithelial cells in co-culture. Our results demonstrate a HIF-1-dependent
      induction of Wnt1 in hypoxic macrophages that undermines autophagy in epithelial
      cells and suggest a role for Wnt signaling and mTOR pathways in the impaired
      epithelial autophagy observed in the mucosa of IBD patients. 

PMID- 24301661
TI  - Current research in transcultural psychiatry in the Nordic countries.
AB  - This article discusses major themes in recent transcultural psychiatric research
      in the Nordic countries from 2008 to 2011: (a) epidemiological studies of
      migration, (b) indigenous populations, and (c) quality of psychiatric care for
      migrants. Over the past several decades, the populations of the Nordic countries,
      Denmark, Finland, Norway, and Sweden, which were relatively homogeneous, have
      become increasingly culturally diverse. Many migrants to Nordic countries have
      been exposed to extreme stress, such as threats of death and/or torture and other
      severe social adversities before, during, and after migration, with potential
      effects on their physical, mental, social, and spiritual health. Growing interest
      in transcultural issues is reflected in the level of scientific research and
      clinical activity in the field by Nordic physicians, psychologists, social
      scientists, demographers, medical anthropologists, as well as other clinicians
      and policy planners. Research includes work with migrants and indigenous
      minorities in the Nordic countries, as well as comparisons with mental health in
      postconflict countries. We conclude by suggesting future directions for
      transcultural psychiatry research and providing guidelines for the education and
      training of future clinicians in the Nordic countries. 

PMID- 24301663
TI  - A partial characterization of the long-wavelength "Activated" far-red absorbing
      form of phytochrome.
AB  - The spectral properties of Pfr in extracts prepared from red-irradiated oat
      tissue are similar to those for Pfr as measured in vivo, with a spectral peak at
      about 732 nm. The presence or absence of Mg(2+) or EDTA in the extraction medium
      is without effect on the spectral properties of the Pfr extracted from red
      irradiated tissue. In contrast, the spectral properties of Pfr formed in vitro in
      extracts of non-irradiated oat tissue cleared of particulate matter are markedly
      different, the absorption peak being at about 725 nm. However, the red
      irradiation of the crude extract prior to its being cleared of particulate
      matter, results in the formation of a Pfr-species with spectral properties
      similar to Pfr as seen in vivo, suggesting the requirement for some particulate
      fraction for the formation of the long-wavelength Pfr form. The long-wavelength
      "activated" form of Pfr once extracted and partially purified is highly stable
      both at 0 degrees  and 25 degrees C. Photoconversion of this long-wavelength form
      of Pfr to Pr initially results in the formation of a Pr species with a peak at
      662 nm. In contrast, the peak location of Pr as isolated from non-irradiated
      tissue is at 667 nm.The 662 nm form of Pr is unstable and with time is
      transformed in a temperature-dependent reaction to a form with a peak at 667 nm.
      At 25 degrees C this reaction is rapid, occurring in minutes, while at 0 degrees 
      4 degrees C it requires a few hours. At 25 degrees C, immediate photoconversion
      of the 662 nm form of Pr back to Pfr results in the reformation of the long
      wavelength form of Pfr. However, after being incubated for 15 min in the Pr form
      the peak shifts to 667 nm and the Pfr subsequently formed exhibits spectral
      characteristics identical to those of Pfr as formed in vitro, i.e., with a peak
      at 725 nm. 

PMID- 24301664
TI  - Ultrastructural changes in the endoplasmic reticulum during dormancy release of
      apple embryos (Pyrus malus L.).
AB  - Apple embryos were treated by cold (0 degrees C) within the fruits, to break
      their dormancy; the controls were treated at 12 degrees C or at 20 degrees C.
      Ultrastructural features of meristematic cells in the embryonic axis were
      compared for each treatment. The organization of the cells of dormant embryos was
      described: Endoplasmic reticulum consisted in some short rough cisternae; lipid
      droplets regularly arranged near the plasmalemma constituted a kind of shell;
      mitochondria had a few cristae; and dictyosomes were rarely observed. All these
      features are typical of dry seeds. After cold treatments, the only evolution
      observed was in the endoplasmic reticulum, where highly organized stacks appeared
      progressively as a function of time at 0 degrees C. An intermediate temperature
      (12 degrees C) induced similar formations in the reticulum but they were rarely
      observed and their degree of organization was lower than that obtained at 0
      degrees C. At 20 degrees C, endoplasmic reticulum resembled that of the dormant
      embryo cells. The relation between the appearance of these structures in the
      reticulum and the disappearance of dormancy induced by cold is discussed. 

PMID- 24301665
TI  - Auxin uptake and action of N-1-naphthylphthalamic acid in corn coleoptiles.
AB  - The validity of a chemiosmotic hypothesis for uptake of weak acids as an
      explanation for the accumulation of auxin by cells has been explored further by
      comparing the uptake of indole-3-acetic acid (IAA) by 1-mm segments of corn (Zea
      mays L.) coleoptiles with that of benzoic acid and two neutral indoles,
      indoleethanol and indoleacetonitrile, which do not ionize. These substances,
      while structurally related to IAA lack both auxin activity and polar transport.
      Uptake of IAA and benzoic acid increase with decreasing external pH, whereas the
      uptake of the two neutral indoles is independent of external pH.Although
      metabolism of IAA, during 90 min or less, is minimal and without significant
      effect on its uptake, metabolism of benzoic acid appears responsible for the
      apparent saturation of benzoic acid uptake at high concentrations. An inhibitor
      of auxin transport, N-1-naphthylphathalamic acid (NPA), stimulates uptake of IAA
      but has no effect on uptake of either benzoic acid or the two neutral indoles.
      Thus, NPA does not affect the driving forces for accumulation of weak acids but
      probably specifically decreases the flux of the auxin anions relative to
      undissociated auxin. Since the electrochemical potential of auxin anions is
      usually higher in than outside cells, blocking the anion flux with NPA would
      enhance auxin uptake. Azide, which abolishes accumulation of both IAA and benzoic
      acid, may simply collapse the pH gradient across the plasma membrane.In the
      absence of NPA, increasing concentrations of auxins or the analogoue beta
      naphthaleneacetic acid (beta-NAA) exert two opposing effects on the uptake of IAA
      depression and stimulation. Stimulation results from saturating the anion flux.
      With uptake fully stimulated by NPA, however, increasing concentrations of auxins
      or analogues only depress uptake of [(3)H]IAA. These results are consistent with
      more than one path for auxin transport each with a different dependence on
      concentration. In depressing NPA-stimulated IAA uptake, the effectiveness of beta
      NAA?IAA?alpha-NAA? benzoic acid, a specificity similar to that of an auxin
      binding site in vitro that has been implicated by others in auxin transport. The
      results support the general hypothesis that cellular auxin uptake and polar
      transport through tissues are chemiosmotically coupled to the electrochemical
      potential of auxin and protons. 

PMID- 24301666
TI  - High frequency fusion of plant protoplasts by electric fields.
AB  - Mesophyll cell protoplasts of Vicia faba were collected by dielectrophoresis in a
      highly inhomogeneous alternating electric field (sine wave, 5 to 10 V peak-to
      peak value, 500 kHz, electrode distance 200 MUm). Under these conditions, the
      cells formed aggregates of two or three on the electrodes or bridges consisting
      of 4 to 6 protoplasts between the electrodes. This "pearl chain" arrangement of
      the cells was only stable for the duration of the applied field. By the
      additional application of a high single field pulse (square wave, 15 V, 50 MUs),
      it was possible to induce cell fusion within the aggregates or bridges. This
      electrically stimulated fusion of cells proceeded at room temperature and under
      physiological pH-conditions, without the use of chemical reagents, and gave a
      high yield. Smaller fused aggregates formed spheres within a few minutes. During
      the dielectrophoretically induced adhesion of the protoplasts to one another, the
      field strength must be chosen such that dielectric breakdown of the membrane is
      avoided, but at the same time, the strength of the subsequently applied single
      field pulse must be high enough to induce dielectric breakdown at the sites of
      contact between the protoplast membranes. From these results, one can conclude
      that in addition to close contact between membranes, the prerequisite for
      electrically stimulated cell fusion is dielectric breakdown which leads to
      changes in the membrane conductance, permeability, and probably fluidity. 

PMID- 24301667
TI  - Reversible heat-inactivation of the calvin cycle: A possible mechanism of the
      temperature regulation of photosynthesis.
AB  - Photosynthetic CO2 fixation rates in leaves and intact chloroplasts of spinach
      measured at 18 degrees -20 degrees  C are substantially decreased by pretreatment
      at temperatures exceeding 20 degrees  C. Mild heating which causes 80% inhibition
      of CO2 fixation does not affect phosphoglyceroacid reduction and causes increases
      in the ATP/ADP ratio and the light-induced transthylakoid proton gradient. The
      inactivation of the CO2 fixation is completely reversible with half-times of
      recovery in the order of 15-20 min. Comparison of steady-state patterns of (14)C
      labeled Calvin cycle intermediates of heat-treated and control samples reveals a
      large increase in the ribulose-1,5-bisphosphate/phosphoglyceroacid ratio and a
      large decrease in the phosphoglyceroacid/triosephosphate ratio. It is concluded
      that inactivation of CO2 fixation occurring at elevated temperatures is caused by
      inhibition of the ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39).
      Measurements of light-induced light scattering changes of thylakoids and of the
      light-induced electrochromic absorption shift show that these signals are
      affected by mild heating in a way which is strictly correlated with the
      inactivation of the CO2 fixation. It is proposed that the function of the
      ribulose-1,5-bisphosphate carboxylase in vivo requires a form of activation that
      involves properties of the thylakoid membrane which are affected by the heat
      treatment. The fact that these changes in thylakoid membrane properties and of
      ribulose-1,5-bisphosphate carboxylase activity are already affected at elevated
      temperatures which can still be considered physiological, and the reversible
      nature of these changes, suggest that they may play a role in temperature
      regulation of the overall photosynthetic process. 

PMID- 24301668
TI  - Characterization of the thylakoid membranes of the tobacco aurea mutant Su/su and
      of three green revertant plants.
AB  - Phenotypic characterizations of the semidominant aurea tobacco (Nicotiana tabacum
      L.) mutant Su/su, the homozygous mutant Su/Su and three green revertants (R1, R2,
      and R3) are presented. The leaf color of Su/su plants varies from yellow to light
      green when grown under high and low energy fluence rates (33.0 and 3.3 W m(-2)),
      respectively. The change in visual phenotype under high-light conditions is
      correlated with decreased content of chlorophyll per leaf area, agranal
      chloroplast ultrastructure, changes in the number of chlorophyll-protein
      complexes, and absence of two or more of the light harvesting chlorophyll
      polypeptides of 25,000-29,000 dalton. The homozygous mutant grown under low light
      was shown to be completely lacking in grana stacks and to be deficient in
      chlorophyll-protein complexes. Revertant R1 was found to be identical to wild
      type plants in all parameters examined (leaf color, chloroplast ultrastructure,
      chlorophyll-protein complexes, chlorophyll-protein complex polypeptides) except
      in chlorophyll content. It did not show an increased chlorophyll and carotenoid
      content as did the wild-type plants when exposed to high light. Revertants R2 and
      R3 were similar to the heterozygous mutant Su/su in most of the parameters
      examined. They yellowed because of a loss of chlorophyll and an increase in the
      amount of carotenoids, had agranal chloroplasts, and had variant chlorophyll
      protein complexes when grown under high light intensities. However, each appeared
      to contain some of the light-harvesting pigment-protein complex polypeptides
      found to be absent in Su/su when grown under high-light conditions. 

PMID- 24301669
TI  - Coordinate induction by UV light of stilbene synthase, phenylalanine ammonia
      lyase and cinnamate 4-hydroxylase in leaves of vitaceae.
AB  - A stilbene synthase catalyzing the formation of resveratrol from 4
      hydroxycinnamoyl-CoA and malonyl-CoA was found in the leaves of several Vitaceae.
      This stilbene synthase and two other enzymes functioning on the route from
      phenylalanine to stilbenes were induced concurrently upon irradiation of the
      leaves with UV light. With leaves of Cissus antarctica, an increase of stilbene
      synthase activity, more than hundred-fold, was observed with a maximum appearing
      15 h after the induction with UV light. 

PMID- 24301670
TI  - Xylan synthetase activity in differentiated xylem cells of sycamore trees (Acer
      pseudoplatanus).
AB  - Particulate enzymic preparations obtained from homogenates of differentiated
      xylem cells isolated from sycamore trees, catalyzed the formation of a
      radioactive xylan in the presence of UDP-D-[U-(14)C]xylose as substrate. The
      synthesized xylan was not dialyzable through Visking cellophane tubing.
      Successive extraction with cold water, hot water and 5% NaOH dissolved
      respectively 15, 5 and 80% of the radioactive polymer. Complete acid hydrolysis
      of the water-insoluble polysaccharide synthesized from UDP-D-[U-(14)C]xylose
      released all the radioactivity as xylose. beta-1,4-Xylodextrins, degree of
      polymerization 2, 3, 4, 5 and 6, were obtained by partial acid hydrolysis (fuming
      HCl or 0.1 M HCl) of radioactive xylan. The polymer was hydrolysed to xylose,
      xylobiose and xylotriose by Driselase which contains 1,4-beta xylanase
      activities. Methylation and then hydrolysis of the xylan released two methylated
      sugars which were identified as di-O-methyl[(14)C]xylose and tri-O-methyl
      [(14)C]xylose, suggesting a 1->4-linked polymer. The linkage was confirmed by
      periodate oxidation studies. The apparent Km value of the synthetase for UDP-D
      xylose was 0.4 mM. Xylan synthetase activity was not potentiated in the presence
      of a detergent. The enzymic activity was stimulated by Mg(2+) and Mn(2+) ions,
      although EDTA in the range of concentrations between 0.01 and 1 mM did not affect
      the reaction rate. It appears that the xylan synthetase system associated with
      membranes obtained from differentiated xylem cells of sycamore trees may serve
      for catalyzing the in vivo synthesis of the xylan main chain during the
      biogenesis of the plant cell wall. 

PMID- 24301671
TI  - Increase of xylan synthetase activity during xylem differentiation of the
      vascular cambium of sycamore and poplar trees.
AB  - The activity of a beta-(1-4)-xylan synthetase, a membrane-bound enzymic system,
      was measured in particulate enzymic preparations (1,000 g and 1,000-100,000 g
      pellets) obtained from homogenates of cambial cells, differentiating xylem cells
      and differentiated xylem cells isolated from actively growing trees of sycamore
      (Acer pseudoplatamus) and poplar (Populus robusta). The specific activity (nmol
      of xylan formed min(-1) mg(-1) of protein) as well as the activity calculated on
      a per cell basis (nmol of xylan formed min(-1) cell(-1)) of this enzymic system,
      markedly increased as cells differentiate from the vascular cambium to xylem.
      This increase is closely correlated with the enhanced deposition of xylan
      occurring during the formation of secondary thickening. The possible control of
      xylan synthesis during the biogenesis of plant cell wall is discussed. 

PMID- 24301672
TI  - Effects of high temperature on the germination of maize (Zea mays L.).
AB  - Poor emergence of maize seedlings, due to high soil temperatures, is a major
      limitation of crop potential in the lowland tropics. Ability to germinate at high
      temperature (>c. 37 degrees  C) is related to the temperature sensitivity of the
      embryo, and there is considerable genotypic variation for this
      character.Respiration and mitochondrial phosphorylation proceed normally in seeds
      imbibing at 41 degrees  C, and ATP levels are adequate for germination. However,
      the specific activities of several important enzymes are lower, and the rate of
      protein synthesis is severely reduced compared with seeds imbibing at 28 degrees 
      C. The depression of the rate of protein synthesis in the embryos of several
      tropical hybrids imbibing at high temperature correlated with their known
      temperature sensitivity. It is concluded that protein synthesis is an especially
      temperature sensitive process in germinating maize embryos, and that this is the
      principal reason for the sensitivity of germinating maize seeds to high
      temperature. 

PMID- 24301673
TI  - Effects of high temperature on protein synthesis during germination of maize (Zea
      mays L.).
AB  - The poor germination of maize seeds at high temperatures (>37 degrees C) is
      related to the low rate of protein synthesis by the embryo. The apparatus of
      translation was not heat-labile when embryos were incubated for 2 h at 41 degrees
      C, and cell free extracts from seeds imbibed for 16 h at this temperature were
      able to translate exogenous mRNA, indicating that ribosomes and other subcellular
      components were present and functional. Analysis of polysome profiles from
      embryos imbibing at high temperature indicated that the low rate of protein
      synthesis was due to the non-availability of active mRNA. 

PMID- 24301674
TI  - An analysis of the action of light on betalain synthesis in the seedling of
      Amaranthus caudatus, var. viridis.
AB  - Accumulation of betalain (amaranthin) in the seedling of Amaranthus caudatus,
      var. viridis, is inducible by light. Since the apparent lag-phase of amaranthin
      accumulation after the onset of light is of the order of 3 h, light induction
      experiments could be performed up to 3 h after the onset of light without
      interference with actual synthesis. The intricate induction phenomena can be
      explained as follows: The inductive light operates through phytochrome and
      through a blue/UV photoreceptor ('cryptochrome'). A phytochrome-dependent 'High
      Irradiance Reaction' is of minor importance. However, there is a strong, specific
      interaction between the light effects mediated through phytochrome and
      cryptochrome in the sense that the 'extent of the reversible response' -
      (response obtained with a particular light treatment terminated with a saturating
      red light pulse) minus (response obtained with the same light treatment when
      terminated with a saturating 756 nm light pulse) -increases with increasing Pfr
      level and total fluence rate during the induction period. It is concluded that
      light induced amaranthin synthesis is, in fact, a convenient biochemical model
      system of photomorphogenesis in the case when phytochrome and cryptochrome
      operate simultaneously in mediating photomorphogenesis. 

PMID- 24301675
TI  - Electrical membrane potential and resistance in photoautotrophic suspension cells
      of Chenopodium rubrum L.
AB  - On photoautotrophically grown, suspension-cultured cells of Chenopodium rubrum L.
      the electrical potential difference V mand the electrical resistance across
      plasmalemma and tonoplast have been measured using one or two intracellular micro
      electrodes. In a mineral test-medium of 5.8 mM ionic strength V mvalues between
      100 and 250 mV, 40% thereof between 170 and 200 mV, and a mean value (+/-S.E.M.)
      of 180.6+/-3.4 mV have been recorded. The average membrane input resistance R
      mwas 269+/-36 MOmega, corresponding to an average membrane resistivity r mof 3.0
      Omegam(2). V mand r mare sensitive to light, temperature, and addition of
      cyanide, suggesting the presence of an electrogenic hyperpolarizing ion pump, and
      are ascribed essentially to the plasmalemma. A hexose-specific saturable
      electrogenic membrane channel is identified through a decrease of V mand r mupon
      addition of hexoses. The hexoseconcentration-dependent depolarization DeltaV
      msaturates at 92 mV and returns half-saturating concentrations (apparent k
      mvalues) of 0.16 mM galactose, 0.28 mM glucose, and 0.48 mM fructose. The
      magnitude of V mand r mwell agrees with pertinent data from mesophyll cells in
      situ (where only V mdata are available) and from photoautotrophic lower plant
      cells. However, V mis markedly higher than reported for heterotrophically grown
      suspension cells of different higher plants (with which r mdata have not been
      reported so far). It is concluded from the present study and a companion paper on
      water transport (Buchner et al., Planta, in press) that photoautotrophically
      grown Chenopodium suspension cells closely resemble mesophyll cells as to cell
      membrane transport properties. 

PMID- 24301676
TI  - Turgor pressure and water transport properties of suspension-cultured cells of
      Chenopodium rubrum L.
AB  - The turgor pressure and water relation parameters were determined in single
      photoautotrophically grown suspension cells and in individual cells of intact
      leaves of Chenopodium rubrum using the miniaturized pressure probe. The
      stationary turgor pressure in suspension-cultured cells was in the range of
      betwen 3 and 5 bar. From the turgor pressure relaxation process, induced either
      hydrostatically (by means of the pressure probe) or osmotically, the halftime of
      water exchange was estimated to be 20+/-10 s. No polarity was observed for both
      ex- and endosmotic water flow. The volumetric elastic modulus, epsilon,
      determined from measurements of turgor pressure changes, and the corresponding
      changes in the fractional cell volume was determined to be in the range of
      between 20 and 50 bar. epsilon increases with increasing turgor pressure as
      observed for other higher plant and algal cells. The hydraulic conductivity, Lp,
      is calculated to be about 0,5-2.10(-6) cm s(-1) bar(-1). Similar results were
      obtained for individual leaf cells of Ch. rubrum. Suspension cells immobilized in
      a cross-linked matrix of alginate (6 to 8% w/w) revealed the same values for the
      half-time of water exchange and for the hydraulic conductivity, Lp, provided that
      the turgor pressure relaxation process was generated hydrostatically by means of
      the pressure probe. Thus, it can be concluded that the unstirred layer from the
      immobilized matrix has no effect on the calculation of Lp from the turgor
      pressure relaxation process, using the water transport equation derived for a
      single cell surrounded by a large external volume. By analogy, this also holds
      true for Lp-values derived from turgor pressure changes generated by the pressure
      probe in a single cell within the leaf tissue. The fair similarity between the Lp
      values measured in mesophyll cells in situ and mesophyll-like suspension cells
      suggests that the water transport relations of a cell within a leaf are not
      fundamentally different from those measured in a single cell. 

PMID- 24301677
TI  - SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal
      muscular atrophy.
AB  - Low levels of survival of motor neuron (SMN) protein lead to spinal muscular
      atrophy (SMA). The major pathological hallmark of SMA is a loss of lower motor
      neurons from spinal cord and peripheral nerve. However, recent studies have
      revealed pathological changes in other cells and tissues of the neuromuscular
      system. Here, we demonstrate intrinsic, SMN-dependent defects in Schwann cells in
      SMA. Myelination in intercostal nerves was perturbed at early- and late
      symptomatic stages of disease in two mouse models of SMA. Similarly, maturation
      of axo-glial interactions at paranodes was disrupted in SMA mice. In contrast,
      myelination of motor axons in the corticospinal tract of the spinal cord occurred
      normally. Schwann cells isolated from SMA mice had significantly reduced levels
      of SMN and failed to express key myelin proteins following differentiation,
      likely due to perturbations in protein translation and/or stability rather than
      transcriptional defects. Myelin protein expression was restored in SMA Schwann
      cells following transfection with an SMN construct. Co-cultures of healthy
      neurons with diseased Schwann cells revealed deficient myelination, suggestive of
      intrinsic defects in Schwann cells, as well as reduced neurite stability.
      Alongside myelination defects, SMA Schwann cells failed to express normal levels
      of key extracellular matrix proteins, including laminin alpha2. We conclude that
      Schwann cells require high levels of SMN protein for their normal development and
      function in vivo, with reduced levels of SMN resulting in myelination defects,
      delayed maturation of axo-glial interactions and abnormal composition of
      extracellular matrix in peripheral nerve. 

PMID- 24301678
TI  - The transcription-splicing protein NonO/p54nrb and three NonO-interacting
      proteins bind to distal enhancer region and augment rhodopsin expression.
AB  - Phototransduction machinery in vertebrate photoreceptors is contained within the
      membrane discs of outer segments. Daily renewal of 10% of photoreceptor outer
      segments requires stringent control of gene expression. Rhodopsin constitutes
      over 90% of the protein in rod discs, and its altered expression or transport is
      associated with photoreceptor dysfunction and/or death. Two cis-regulatory
      sequences have been identified upstream of the rhodopsin transcription start
      site. While the proximal promoter binds to specific transcription factors,
      including NRL and CRX, the rhodopsin enhancer region (RER) reportedly contributes
      to precise and high-level expression of rhodopsin in vivo. Here, we report the
      identification of RER-bound proteins by mass spectrometry. We validate the
      binding of NonO (p54(nrb)), a protein implicated in coupling transcription to
      splicing, and three NonO-interacting proteins-hnRNP M, Ywhaz and Ppp1ca. NonO and
      its interactors can activate rhodopsin promoter in HEK293 cells and function
      synergistically with NRL and CRX. DNA-binding domain of NonO is critical for
      rhodopsin promoter activation. Chromatin immunoprecipitation followed by deep
      sequencing (ChIP-seq) analysis demonstrates high occupancy of NonO at rhodopsin
      and a subset of phototransduction genes. Furthermore, shRNA knockdown of NonO in
      mouse retina leads to loss of rhodopsin expression and rod cell death, which can
      be partially rescued by a C-terminal NonO construct. RNA-seq analysis of the NonO
      shRNA-treated retina revealed splicing defects and altered expression of genes,
      specifically those associated with phototransduction. Our studies identify an
      important contribution of NonO and its interacting modulator proteins in
      enhancing rod-specific gene expression and controlling rod homeostasis. 

PMID- 24301680
TI  - FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular
      and mouse models of Huntington disease.
AB  - Huntington disease (HD) is a genetic neurodegenerative disorder for which there
      is currently no cure and no way to stop or even slow the brain changes it causes.
      In the present study, we aimed to investigate whether FTY720, the first approved
      oral therapy for multiple sclerosis, may be effective in HD models and eventually
      constitute an alternative therapeutic approach for the treatment of the disease.
      Here, we utilized preclinical target validation paradigms and examined the in
      vivo efficacy of chronic administration of FTY720 in R6/2 HD mouse model. Our
      findings indicate that FTY720 improved motor function, prolonged survival and
      reduced brain atrophy in R6/2 mice. The beneficial effect of FTY720
      administration was associated with a significant strengthening of neuronal
      activity and connectivity and, with reduction of mutant huntingtin aggregates,
      and it was also paralleled by increased phosphorylation of mutant huntingtin at
      serine 13/16 residues that are predicted to attenuate protein toxicity. 

PMID- 24301679
TI  - Hsp90 inhibition protects against inherited retinal degeneration.
AB  - The molecular chaperone Hsp90 is important for the functional maturation of many
      client proteins, and inhibitors are in clinical trials for multiple indications
      in cancer. Hsp90 inhibition activates the heat shock response and can improve
      viability in a cell model of the P23H misfolding mutation in rhodopsin that
      causes autosomal dominant retinitis pigmentosa (adRP). Here, we show that a
      single low dose of the Hsp90 inhibitor HSP990 enhanced visual function and
      delayed photoreceptor degeneration in a P23H transgenic rat model. This was
      associated with the induction of heat shock protein expression and reduced
      rhodopsin aggregation. We then investigated the effect of Hsp90 inhibition on a
      different type of rod opsin mutant, R135L, which is hyperphosphorylated, binds
      arrestin and disrupts vesicular traffic. Hsp90 inhibition with 17-AAG reduced the
      intracellular accumulation of R135L and abolished arrestin binding in cells. Hsf
      1(-/-) cells revealed that the effect of 17-AAG on P23H aggregation was dependent
      on HSF-1, whereas the effect on R135L was HSF-1 independent. Instead, the effect
      on R135L was mediated by a requirement of Hsp90 for rhodopsin kinase (GRK1)
      maturation and function. Importantly, Hsp90 inhibition restored R135L rod opsin
      localization to wild-type (WT) phenotype in vivo in rat retina. Prolonged Hsp90
      inhibition with HSP990 in vivo led to a posttranslational reduction in GRK1 and
      phosphodiesterase (PDE6) protein levels, identifying them as Hsp90 clients. These
      data suggest that Hsp90 represents a potential therapeutic target for different
      types of rhodopsin adRP through distinct mechanisms, but also indicate that
      sustained Hsp90 inhibition might adversely affect visual function. 

PMID- 24301682
TI  - Two-colour hard X-ray free-electron laser with wide tunability.
AB  - Ultrabrilliant, femtosecond X-ray pulses from X-ray free-electron lasers (XFELs)
      have promoted the investigation of exotic interactions between intense X-rays and
      matters, and the observation of minute targets with high spatio-temporal
      resolution. Although a single X-ray beam has been utilized for these experiments,
      the use of multiple beams with flexible and optimum beam parameters should
      drastically enhance the capability and potentiality of XFELs. Here we show a new
      light source of a two-colour double-pulse (TCDP) XFEL in hard X-rays using
      variable-gap undulators, which realizes a large and flexible wavelength
      separation of more than 30% with an ultraprecisely controlled time interval in
      the attosecond regime. Together with sub-10-fs pulse duration and multi-gigawatt
      peak powers, the TCDP scheme enables us to elucidate X-ray-induced ultrafast
      transitions of electronic states and structures, which will significantly
      contribute to the advancement of ultrafast chemistry, plasma and astronomical
      physics, and quantum X-ray optics. 

PMID- 24301681
TI  - Hypoxia-induced epigenetic modifications are associated with cardiac tissue
      fibrosis and the development of a myofibroblast-like phenotype.
AB  - Ischemia caused by coronary artery disease and myocardial infarction leads to
      aberrant ventricular remodeling and cardiac fibrosis. This occurs partly through
      accumulation of gene expression changes in resident fibroblasts, resulting in an
      overactive fibrotic phenotype. Long-term adaptation to a hypoxic insult is likely
      to require significant modification of chromatin structure in order to maintain
      the fibrotic phenotype. Epigenetic changes may play an important role in
      modulating hypoxia-induced fibrosis within the heart. Therefore, the aim of the
      study was to investigate the potential pro-fibrotic impact of hypoxia on cardiac
      fibroblasts and determine whether alterations in DNA methylation could play a
      role in this process. This study found that within human cardiac tissue, the
      degree of hypoxia was associated with increased expression of collagen 1 and
      alpha-smooth muscle actin (ASMA). In addition, human cardiac fibroblast cells
      exposed to prolonged 1% hypoxia resulted in a pro-fibrotic state. These hypoxia
      induced pro-fibrotic changes were associated with global DNA hypermethylation and
      increased expression of the DNA methyltransferase (DNMT) enzymes DNMT1 and
      DNMT3B. Expression of these methylating enzymes was shown to be regulated by
      hypoxia-inducible factor (HIF)-1alpha. Using siRNA to block DNMT3B expression
      significantly reduced collagen 1 and ASMA expression. In addition, application of
      the DNMT inhibitor 5-aza-2'-deoxycytidine suppressed the pro-fibrotic effects of
      TGFbeta. Epigenetic modifications and changes in the epigenetic machinery
      identified in cardiac fibroblasts during prolonged hypoxia may contribute to the
      pro-fibrotic nature of the ischemic milieu. Targeting up-regulated expression of
      DNMTs in ischemic heart disease may prove to be a valuable therapeutic approach. 

PMID- 24301683
TI  - Corona charge selective micelle degradation catalyzed by P. cepacia lipase
      isoforms.
AB  - Micelles derived from poly(epsilon-caprolactone) (PCL) poly(ethylene glycol)(PEG)
      diblock copolymers (HO-PCLn-b-PEG32-RX, R = -O(CH2)3S(CH2)2-; X = -CO2(-), -SO3(
      ), -NH3(+)) show corona charge selective degradation catalyzed by P. cepacia
      lipase isoforms.

PMID- 24301684
TI  - Bromodeoxyuridine (BrdU)-label-retaining cells in mouse terminal bronchioles.
AB  - Adult male mice were continuously treated with bromodeoxyuridine (BrdU) for 1, 2,
      or 4 weeks by an osmotic pump. To detect BrdU-label-retaining cells (LRCs),
      putative progenitor/stem cells, other animals were continuously treated with BrdU
      for 2 weeks, and were then kept without any treatments for 2, 6, or 18 months.
      The lungs were fixed with 4% paraformaldehyde, and were paraffin-embedded. We
      observed terminal bronchioles with BrdU immunostaining alone or with BrdU
      immunostaining accompanying immunostaining for Clara cell secretory protein
      (CCSP), forkhead box protein J1 (FoxJ1), or calcitonin gene-related peptide
      (CGRP). The average incidences of BrdU-incorporated cells in the terminal
      bronchioles after 1, 2, and 4 weeks of continuous BrdU infusion were 6.2%, 11.9%,
      and 23.1%, respectively. Most BrdU-incorporated cells in these periods were CCSP
      immunoreactive (91.7%, 91.3%, and 88.2%, respectively), which means progenitor
      function of Clara cells. FoxJ1-immunoreactive BrdU-incorporated cells were fewer
      (5.4%, 3.0%, 2.7%, respectively). The average incidences of BrdU-LRCs in the
      terminal bronchioles after 2, 6, and 18 months were 7.2%, 4.3, and 2.7%,
      respectively. Most BrdU-LRCs were CCSP-immunoreactive (91.0%, 92.7%, and 89.6%,
      respectively), and FoxJ1-immunoreactive BrdU-LRCs were fewer (6.0%, 5.7%, and
      2.1%, respectively). CGRP-positive BrdU-incorporated cells were occasional. CGRP
      positive BrdU-LRCs were detected in 17.6% of neuroepithelial bodies (NEBs) at 2
      months, but disappeared at 6 months. BrdU-positive stem cell candidates, which
      locate at the brochiolo-alveolar duct junction or cover NEB, were few throughout
      this study. In conclusion, in the lungs treated only with BrdU, CCSP
      immunoreactive cells are important to maintain homeostasis in the terminal
      bronchiolar epithelium.

PMID- 24301685
TI  - Dosing of enoxaparin for venous thromboembolism prophylaxis in obese patients.
AB  - OBJECTIVE: To evaluate the appropriate dosing of enoxaparin as a venous
      thromboembolism (VTE) prophylaxis in hospitalized obese patients. DATA SOURCES:
      Literature articles were accessed through MEDLINE (1946 to August week 1, 2013)
      and EMBASE (1980 to 2013 week 33) searches using the terms enoxaparin, obesity,
      and thromboprophylaxis. STUDY SELECTION AND DATA EXTRACTION: All articles that
      involved human subjects and were published in the English language, evaluating
      the appropriate dose of enoxaparin for VTE prophylaxis in hospitalized, obese
      patients were included. DATA SYNTHESIS: Appropriate enoxaparin dosing for
      thromboprophylaxis in adult patients is 40 mg subcutaneously daily or 30 mg
      subcutaneously twice daily. Although obesity is considered one of the risk
      factors for thromboembolism, morbidly obese patients were excluded from most
      clinical trials; therefore, the appropriate enoxaparin preventive dose is not
      clear in this population. In recent years, the appropriate dose of enoxaparin for
      VTE prophylaxis in obese patients has been evaluated in 3 clinical studies. All
      studies enrolled patients with various risk factors for thromboembolism and
      evaluated different enoxaparin dosing regimens. End point analyses were all based
      on anti-Xa levels. CONCLUSIONS: Due to a lack of well-designed prospective,
      randomized control studies, varying doses of enoxaparin are used for VTE
      prophylaxis in hospitalized, obese patients. All doses studied were monitored
      using anti-Xa levels. Patient follow-up was of short duration in all studies and
      did not show long-term effectiveness of enoxaparin. Prospective, randomized
      controlled studies are warranted to show efficacy and safety of one dosage
      regimen over another.

PMID- 24301686
TI  - Evaluation of dabigatran exposures reported to poison control centers.
AB  - BACKGROUND: Dabigatran is a novel oral anticoagulant for which a well-defined
      range of toxicity and proven antidote has not been established. OBJECTIVE: The
      primary objective of this study was to characterize dabigatran exposures reported
      to poison centers by dose ingested, clinical effects, treatments used, and
      managment sites to gain a better understanding of patient outcomes. METHODS: A
      retrospective database review was conducted for dabigatran exposures reported to
      the National Poison Data System for the American Association of Poison Control
      Centers (AAPCC) over the period October 2010 to December 2012. RESULTS: There
      were 802 human dabigatran exposures involving adults predominantly (91% of
      cases). Exposure chronicity was acute in 43%, acute-on-chronic in 46%, and
      chronic in 11%, with the most common reason for an exposure call being an
      unintentional therapeutic error (70.6%). The most common management sites were on
      site in 72% of cases and within a health care facility for 26%. Bleeding events
      and coagulopathies were the most commonly observed clinical effects. Treatments
      administered included activated charcoal, blood and coagulation products,
      hemodialysis, and supportive measures. Confirmed outcomes included death in 13
      patients (1.6%), major effects in 23 (2.9%), and moderate effects in 50 (6.2%).
      More severe outcomes were significantly associated with adverse drug reactions,
      patients >=65 years of age, those treated with blood and coagulation products
      and/or dialysis, and renal dysfunction (P < .05). Children experienced few
      moderate effects and no major effects or deaths. CONCLUSIONS: Severe outcomes
      from dabigatran exposures were not common, occurring in approximately 5% of
      cases.

PMID- 24301687
TI  - Assessment of drug-induced torsade de pointes risk for hospitalized high-risk
      patients receiving QT-prolonging agents.
AB  - BACKGROUND: Although risk factors for torsade de pointes (TdP) are known,
      identifying hospitalized patients at greatest risk for QTcP who should receive
      cardiac monitoring is poorly defined. OBJECTIVES: Describe the prevalence of risk
      for TdP in patients and associations between risk factors and QTc prolongation
      (QTcP) at a tertiary teaching hospital. METHODS: This retrospective analysis
      assessed physiological and pharmacological risk factors for TdP of adult patients
      receiving >=1 QTc-prolonging medications (QTcMed) during hospitalization. The
      QTcMeds were stratified by risk for causing TdP (probable, possible, and
      conditional). Baseline electrocardiograms (ECGs) were assessed for QTcP
      associated with risk for TdP. RESULTS: During a 6-month period, 12,401 (51%)
      hospitalizations received >=1 QTcMed. A baseline ECG was obtained for 2381 (19%)
      patients. A total of 386 (16%) patients with a baseline ECG were found to have
      QTcP. Significant associations for QTcP were found with the following
      physiological risk factors: female (P = .021), left-ventricular ejection fraction
      <40% (P < .0001), cardiac arrest (P < .0001), and cardioversion (P = .007).
      Significantly more patients with QTcP (n = 209, 54%) received probable-risk
      QTcMeds than those without QTcP (n = 542, 27%; P < .0001). Probable-risk QTcMeds
      administered alone or concomitantly with other QTcMeds were more frequently
      associated with QTcP. No documented cases of TdP were identified. CONCLUSIONS: Of
      the population receiving QTcMeds, only a small portion had a baseline ECG,
      identifying a large population at risk of QTcP without appropriate monitoring.
      Patients with cardiac disease receiving probable-risk QTcMeds were associated
      with the highest risk of QTcP and should be monitored closely.

PMID- 24301688
TI  - Design of advanced porous graphene materials: from graphene nanomesh to 3D
      architectures.
AB  - In order to make full utilization of the high intrinsic surface area of graphene,
      recently, porous graphene materials including graphene nanomesh, crumpled
      graphene and graphene foam, have attracted tremendous attention and research
      interest, owing to their exceptional porous structure (high surface area, and
      high pore volume) in combination with the inherent properties of graphene, such
      as high electronic conductivity, good thermal stability, and excellent mechanical
      strength. Interestingly, porous graphene materials and their derivatives have
      been explored in a wide range of applications in the fields of electronic and
      photonic devices, energy storage, gas separation/storage, oil absorption and
      sensors. This article reviews recent progress in the synthesis, characterization,
      properties, and applications of porous graphene materials. We aim to highlight
      the importance of designing different porous structures of graphene to meet
      future challenges, and the trend on future design of porous graphene materials is
      analyzed. 

PMID- 24301689
TI  - Twenty-five years.

PMID- 24301690
TI  - Cosmology and therapy.
AB  - Sociological concepts are used to demonstrate applications of views of the cosmos
      to everyday living. Optimal recovery in therapy is defined as increased
      participation and increased life-satisfaction in family and society, with
      meaningful motivation and orientation to the universe.Cosmology and therapy
      concepts are applied to five different kinds of marital relationships in order to
      clarify possibilities and define contrasts. Family processes which evolve as
      shifts in views of the cosmos, beliefs, and behavior occur are described.
      Strengths and weaknesses of this therapy are discussed, and attention is paid to
      ways in which beliefs provide motivation, meaning, and direction for behavior. 

PMID- 24301691
TI  - Macrocosm to microcosm: Toward a systemic model of personality.
AB  - This paper attempts to: (1) provide a paradigm through which to understand the
      human self and, (2) bring some order out of the variety of theories of
      personality and strategies of change used in clinical practice today. Drawing on
      modern physics and general systems theory, a multi-leveled, systemic model
      incorporating physical, psychological, and spiritual dimensions is proposed and
      then applied to a representative clinical case. Implications of this model for
      clinical work and for a spiritual understanding of personality are elaborated. 

PMID- 24301692
TI  - Twentieth-century attitudes toward masturbation.
AB  - This article demonstrates the progress that medicine, psychiatry, religion, and
      anthropology have made toward a variant perspective, of masturbation. Researchers
      documented the suffering and damage caused by classically ingrained religious and
      medical distortions.The "secret sin" of Judeo-Christianity and the "social
      disease" of nineteenth-century medicine has paradoxially become the therapy for
      various forms of psychosexual dysfunction. Catholic, Protestant, and Jewish
      denominations polarize opinions from rigorous orthodoxy to unconditional
      acceptance of this psychosexual behavior as a source of emotional homeostasis. 

PMID- 24301693
TI  - The DSM-III and pastoral practice.
AB  - This essay provides a conceptual bridge between psychiatry and pastoral practice
      which may facilitate cooperative efforts. The conceptual link is the theological
      and psychiatric answer to the question, "What is personhood?" found in the
      biblical doctrine of personhood and theDiagnostic and Statistical Manual of
      Mental Disorders, 3rd Edition. The essay argues that both views are holistic,
      compatible, and provide a base for cooperative effort. 

PMID- 24301694
TI  - Illness theodicies in the New Testament.
AB  - The New Testament writers advocate or at least mention six different religious
      explanations for the origin of sickness. First, Satan may thus victimize the
      innocent. Second, God may send sickness as a punishment for the sufferer's sins.
      Third, God may send sickness to punish one's parents' sins. Fourth, God may so
      punish one's own sins committed in a previous life. Fifth, God may inflict
      illness in order to show his power by subsequent healing. Sixth, God may inflict
      illness in order to show his power by sustaining the sufferer through the illness
      instead of healing it. 

PMID- 24301695
TI  - The Jewish patient in a non-Jewish hospital.
AB  - The healing of the sick is a jewish religious precept. The present paper
      discusses the special needs of a hospitalized Jewish patient, describes a "Jewish
      Patient's Bill of Rights," and suggests that the needs of Jewish patients, such
      as kosher food and religious services in a hospital environment, be provided
      wherever possible. 

PMID- 24301696
TI  - Development of oral and branchial muscles in lancelet larvae of Branchiostoma
      japonicum.
AB  - The perforated pharynx has generally been regarded as a shared characteristic of
      chordates. However, there still remains phylogenetic ambiguity between the cilia
      driven system in invertebrate chordates and the muscle-driven system in
      vertebrates. Giant larvae of the genus Asymmetron were reported to develop an
      orobranchial musculature similar to that of vertebrates more than 100 years ago.
      This discovery might represent an evolutionary link for the chordate branchial
      system, but few investigations of the lancelet orobranchial musculature have been
      completed since. We studied staged larvae of a Japanese population of
      Branchiostoma japonicum to characterize the developmental property of the
      orobranchial musculature. The larval mouth and the unpaired primary gills develop
      well-organized muscles. These muscles function only as obturators of the openings
      without antagonistic system. As the larval mouth enlarged posteriorly to the
      level of the ninth myomere, the oral musculature was fortified accordingly
      without segmental patterning. In contrast, the iterated branchial muscles
      coincided with the dorsal myomeric pattern before metamorphosis, but the pharynx
      was remodeled dynamically irrespective of the myomeric pattern during
      metamorphosis. The orobranchial musculature disappeared completely during
      metamorphosis, and adult muscles in the oral hood and velum, as well as on the
      pterygial coeloms developed independently. The lancelet orobranchial musculature
      is apparently a larval adaptation to prevent harmful intake. However, vestigial
      muscles appeared transiently with the secondary gill formation suggest a
      bilateral ancestral state of muscular gills, and a segmental pattern of
      developing branchial muscles without neural crest and placodal contributions is
      suggestive of a precursor of vertebrate branchiomeric pattern.

PMID- 24301697
TI  - Different methodologies in the assessment of identity: Congruence between self
      report and interview techniques?
AB  - Convergent-divergent validity and reliability estimates for clinical interview
      and self-report measures of ego identity were obtained. Twenty-three males and 25
      females completed an extended version of the Ego Identity Interview [H. D.
      Grotevant, W. Thorebecke, and M. C. Meyer (1982) "An Extension of Marcia's
      Identity Status Interview into the Interpersonal Domain,"Journal of Youth and
      Adolescence 11: 33-48] and the extended version of the Objective Measure of Ego
      Identity Status [H. D. Grotevant and G. R. Adams (1984) "Development of an
      Objective Measure to Assess Ego-Identity in Adolescence: Validation and
      Replication,"Journal of Youth and Adolescence, 13: 419-438]. While the two
      measures were expected to converge, little convergence was observed. The findings
      suggest that the two measures may be (a) assessing relatively distinct forms of
      ego identity, or (b) that the ego-identity construct as measured by the process
      (exploration) and outcome (commitment) dimensions needs further theoretical
      examination. 

PMID- 24301698
TI  - Relationship of life events and social support with psychological dysfunction
      among adolescents.
AB  - Relationships among major life events, perceived social support, and
      psychological disorder were assessed in a sample of older adolescents. Negative
      life events and satisfaction with social support were significantly and
      independently related to a range of psychological symptoms. Further, the
      relationship between negative events and disorder was moderated by gender, the
      types of events experienced, and anticipated change in the psychosocial
      environment. The importance of the use of standardized and psychometrically sound
      measures of life events, social support, and psychological disorder is
      highlighted. 

PMID- 24301699
TI  - Sex role strain among kibbutz adolescents and adults: A developmental
      perspective.
AB  - In spite of a commitment to equality, the kibbutz is a male-dominated society
      with highly differentiated sex roles. Has this gap between ideals and reality
      created sex role strain for kibbutz-born adolescents and adults? Previous kibbutz
      studies have suggested that sex role strain may be the most intense among adult
      kibbutz women. Based on Erik Erikson's developmental model, however, we
      hypothesized that adolescent females would experience significantly greater sex
      role strain than other kibbutz members, including adult women. Adolescent and
      adult males and females were tested using Loevinger's ego development test. The
      sex role items of the test were used to construct a new measure of sex role
      strain. The global index included the following submeasures: avoidance of sex
      role issues; expression of intellectual, emotional, or behavioral sex role
      conflict; and evaluative attitudes toward male roles and female roles.
      Significant cohort or sex differences were found on the global index and on all
      submeasures of sex role strain. The findings indicate that sex role strain is
      greatest among adolescent females, followed by adolescent males. Adult kibbutz
      women, however, are significantly more likely to focus their dissatisfaction in
      the area of actual role behavior rather than in terms of how they intellectually
      conceptualize kibbutz sex roles, as is the case for adolescents and adult males. 

PMID- 24301700
TI  - Teenagers' perception of agreement over family expenditures, employment, and
      family life.
AB  - Teenagers' perspective of disagreement over family finances and related factors
      were investigated. Involvement of teenagers in employment and percentage of
      earnings kept for personal use were examined. Reasons for employment affected
      disagreement over finances, whereas family income had no important effect on
      disagreement over finances in multivariate analysis. Disagreement over finances
      was important in explaining variation in satisfaction with money management in
      the family and in satisfaction with family life. Results have implication for
      reducing stress in family life and for contributing to theory on family resource
      management and adolescent development. 

PMID- 24301701
TI  - Hungarian adolescents' self-concept.
AB  - Hungarian and United States adolescents' self-image was studied using the Offer
      Self-Image Questionnaire (OSIQ). In Hungary, 1,163 younger and older male and
      female adolescents were studied using a Hungarian translation of the OSIQ.
      Analyses of endorsement patterns of OSIQ items showed that Hungarian and American
      adolescents endorsed many items in the same way. Similarities in endorsement
      patterns were much more common between the two countries than were differences.
      Analyses of OSIQ scales showed that for most scales younger Hungarian adolescents
      reported better adjustment than younger American adolescents. Differences were
      not as great or reversed in the older age groups. Implications for cross-cultural
      studies of adolescent self-image were drawn based on these results. 

PMID- 24301702
TI  - The mechanism of Rubisco activase: Insights from studies of the properties and
      structure of the enzyme.
AB  - Rubisco, the primary carboxylating enzyme in photosynthesis, must be activated to
      catalyze CO2 fixation. The concept of an 'activase', a specific protein for
      activating Rubisco, was first introduced in 1985 based largely on biochemical and
      genetic studies of a high CO2-requiring mutant of Arabidopsis (Salvucci et al.
      (1985) Photosynth Res 7: 193-201). Over the past ten years, details about the
      occurrence, structure, and properties of Rubisco activase have been elucidated.
      However, the mechanism of action of Rubisco activase remains elusive. This review
      discusses the need for and function of Rubisco activase and summarizes
      information about the properties and structure of Rubisco activase. The
      information is evaluated in the context of the mechanism of Rubisco activase. 

PMID- 24301703
TI  - The efficiency of electron transfer from QA (-) to the donor side of Photosystem
      II decreases during induction of photosynthesis: Evidences from chlorophyll
      fluorescence and photoacoustic techniques.
AB  - The amplitudes ratio of the fast and slow phases (Afast/Aslow) in the kinetics of
      the dark relaxation of variable chlorophyll fluorescence (FV) was studied after
      various periods of illumination of dark-adapted primary barley leaves.
      Simultaneously, photosynthetic activity was monitored using the photoacoustic
      technique and the photochemical and non-photochemical fluorescence quenching
      parameters. The ratio Afast/Aslow changed with the preceding illumination time in
      a two-step manner. During the first stage of photosynthetic induction (0-20 s of
      illumination), characterized by a drop in O2-dependent photoacoustic signal
      following an initial spike and by a relatively stable small value of
      photochemical FV quenching, the ratio Afast/Aslow remained practically unaltered.
      During the second stage (20-60 s of illumination), when both the rate of O2
      evolution and the photochemical FV quenching were found to be sharply developed,
      a marked increase in the above ratio was also observed. A linear correlation was
      found between the value of the photochemical quenching and the ratio Afast/Aslow
      during the second phase of photosynthetic induction. It is concluded that the
      slow phase appearing in the kinetics of FV dark relaxation is not due to the
      existence of Photosystem II reaction centres lacking the ability to reduce
      P700(+) with high rates, but is instead related to the limitation of electron
      release from Photosystem I during the initial stage of the induction period of
      photosynthesis. This limitation keeps the intersystem electron carriers in the
      reduced state and thus increases the probability of back electron transfer from
      QA (-) to the donor side of Photosystem II. 

PMID- 24301704
TI  - Import and assembly of the alpha and beta-polypeptides of the light-harvesting
      complex I (B870) in the membrane system of Rhodobacter capsulatus investigated in
      an in vitro translation system.
AB  - Transcripts of the genes pufBA, pufB or pufA from Rhodobacter capsulatus were
      translated in a cell-free system of R. capsulatus. The incorporation of the
      nascent polypeptides LHIalpha and beta in various types of membranes and the
      assembly of the light-harvesting (LH) complex I (B870) were investigated. The
      highest rate of stable incorporation of LHIalpha and beta into the membrane was
      observed with membranes from the wild type strain grown under chemotrophic
      conditions. Addition of membranes from cells defective in biosynthesis of pigment
      binding proteins resulted in a less efficient or less stable incorporation of
      LHIalphabeta. The single polypeptides LHIalpha or beta were synthesized and
      inserted into the membrane but were extractable to a higher percentage by 6 M
      urea than the pairwise inserted LHI polypeptides.If the ribosomes and the S135
      extract were depleted of DnaK the rate of synthesis of both polypeptides,
      LHIalpha and beta, was strongly reduced. Removal of GroEL from the cell-free
      system did not impair the synthesis and membrane association of both proteins,
      but affected the stable insertion. A high percentage of the LHIalphabeta
      polypeptides became extractable by 6 M urea if the cell-free system was depleted
      of GroEL. Addition of GroEL to the cell-free system restored the capacity of
      stable insertion of both proteins into the membrane. GroEL interacted with
      LHIalpha and beta before membrane targeting as shown by immunological means.A
      protein fraction, which can be removed from the membrane with a low-salt buffer,
      supported the effective and stable incorporation of LHIalphabeta into the
      membrane. It is concluded that the assembly of the LHI complex in the membrane
      system of R. capsulatus is a multistep process guided and supported by
      polypeptides located in the cytoplasm and in the membrane. In the cell-free in
      vitro system not only the correct insertion of the LHI polypeptides but also an
      assembly with bacteriochlorophyll was observed. BChl was synthesized from delta
      amino levulinate in the cell free system. 

PMID- 24301705
TI  - An isolated reaction center complex from the green sulfur bacterium Chlorobium
      vibrioforme can photoreduce ferredoxin at high rates.
AB  - Chlorosome-depleted membranes and a reaction center complex with well-defined
      subunit composition were prepared from the green sulfur bacterium Chlorobium
      vibrioforme under anaerobic conditions. The reaction center complex contains a 15
      kDa polypeptide with the N-terminal amino acid sequence MEPQLSRPETASNQVR/. This
      sequence is nearly identical to the N-terminus of the pscD gene product from
      Chlorobium limicola (Hager-Braun et al. (1995) Biochemistry 34: 9617-9624). In
      the presence of ferredoxin and ferredoxin:NADP(+) oxidoreductase, the membranes
      and the isolated reaction center complex photoreduced NADP(+) at rates of 333 and
      110 MUmol (mg bacteriochlorophyll a)(-1) h(-1), respectively. This shows that the
      isolated reaction center complex contains all the components essential for steady
      state electron transport. Midpoint potentials at pH 7.0 of 160 mV for cytochrome
      c 551 and of 245 mV for P840 were determined by redox titration. Antibodies
      against cytochrome c 551 inhibit NADP(+) reduction while antibodies against the
      bacteriochlorophyll a-binding Fenna-Matthews-Olson protein do not. 

PMID- 24301706
TI  - Electron transfer in reaction centers of Rhodobacter sphaeroides and Rhodobacter
      capsulatus monitored by fluorescence of the bacteriochlorophyll dimer.
AB  - Spectral and kinetic characteristics of fluorescence from isolated reaction
      centers of photosynthetic purple bacteria Rhodobacter sphaeroides and Rhodobacter
      capsulatus were measured at room temperature under rectangular shape of
      excitation at 810 nm. The kinetics of fluorescence at 915 nm reflected redox
      changes due to light and dark reactions in the donor and acceptor quinone complex
      of the reaction center as identified by absorption changes at 865 nm
      (bacteriochlorophyll dimer) and 450 nm (quinones) measured simultaneously with
      the fluorescence. Based on redox titration and gradual bleaching of the dimer,
      the yield of fluorescence from reaction centers could be separated into a time
      dependent (originating from the dimer) and a constant part (coming from
      contaminating pigment (detached bacteriochlorin)). The origin was also confirmed
      by the corresponding excitation spectra of the 915 nm fluorescence. The ratio of
      yields of constant fluorescence over variable fluorescence was much smaller in
      Rhodobacter sphaeroides (0.15+/-0.1) than in Rhodobacter capsulatus (1.2+/-0.3).
      It was shown that the changes in fluorescence yield reflected the disappearance
      of the dimer and the quenching by the oxidized primary quinone. The redox changes
      of the secondary quinone did not have any influence on the yield but excess
      quinone in the solution quenched the (constant part of) fluorescence. The
      relative yields of fluorescence in different redox states of the reaction center
      were tabulated. The fluorescence of the dimer can be used as an effective tool in
      studies of redox reactions in reaction centers, an alternative to the
      measurements of absorption kinetics. 

PMID- 24301707
TI  - Photoinactivation of photosystem II by cumulative exposure to short light pulses
      during the induction period of photosynthesis.
AB  - Photoinactivation of Photosystem (PS) II in vivo was investigated by cumulative
      exposure of pea, rice and spinach leaves to light pulses of variable duration
      from 2 to 100 s, separated by dark intervals of 30 min. During each light pulse,
      photosynthetic induction occurred to an extent depending on the time of
      illumination, but steady-state photosynthesis had not been achieved. During
      photosynthetic induction, it is clearly demonstrated that reciprocity of
      irradiance and duration of illumination did not hold: hence the same cumulative
      photon exposure (mol m(-2)) does not necessarily give the same extent of
      photoinactivation of PS II. This contrasts with the situation of steady-state
      photosynthesis where the photoinactivation of PS II exhibited reciprocity of
      irradiance and duration of illumination (Park et al. (1995) Planta 196: 401-411).
      We suggest that, for reciprocity to hold between irradiance and duration of
      illumination, there must be a balance between photochemical (qP) and non
      photochemical (NPQ) quenching at all irradiances. The index of susceptibility to
      light stress, which represents an intrinsic ability of PS II to balance
      photochemical and non-photochemical quenching, is defined by the quotient (1
      qP)/NPQ. Although constant in steady-state photosynthesis under a wide range of
      irradiance (Park et al. (1995). Plant Cell Physiol 36: 1163-1169), this index of
      susceptibility for spinach leaves declined extremely rapidly during
      photosynthetic induction at a given irradiance, and, at a given cumulative photon
      exposure, was dependent on irradiance. During photosynthetic induction, only
      limited photoprotective strategies are developed: while the transthylakoid pH
      gradient conferred some degree of photoprotection, neither D1 protein turnover
      nor the xanthophyll cycle was operative. Thus, PS II is more easily
      photoinactivated during photosynthetic induction, a phenomenon that may have
      relevance for understorey leaves experiencing infrequent, short sunflecks. 

PMID- 24301708
TI  - Improved 5-step modeling of the Photosystem II S-state mechanism in
      cyanobacteria.
AB  - We present a model of the S-state mechanism, as well as an improved eigenvalue
      analysis, that integrate into a coherent ensemble several features found since
      the S-state model was initially developed. These features include the presence of
      S-1, deactivations in the dark interval between flashes, and the change in the
      number of active PS II centers by photoinhibition or photoactivation. A new
      feature is the capacity to predict the steady-state distribution of S-states
      under conditions of steady photoinhibition or photoactivation. The improved
      eigenvalue analysis allowed the calculation of the initial S-state distribution.
      In addition, the model resolved 'true' photochemical misses from apparent misses
      due to deactivations in the dark interval between flashes. The model suggested
      that most of the misses that are commonly reported are due to deactivations, and
      not to an intrinsic inefficiency of the photochemical mechanism of PS II. Because
      models that allow double-hits encompassing the S2 to S3 transition often predict
      negative initial quantities of S2 in cyanobacteria, our proposed model
      specifically prohibited them. The model accounts for inhomogeneous misses and a
      steady-state distribution of the type (S2)~(S1)>(S3)~(S0). This 5-step model uses
      only 4 probabilities, and is therefore easy to handle. The use of this model is
      critical for the analysis of several cyanobacterial strains, as well as for any
      species that show non-negligible deactivations in the dark interval between
      flashes. 

PMID- 24301709
TI  - Circadian oscillations of Lhc mRNAs in a photoautotrophic cell culture of
      Lycopersicon peruvianum.
AB  - Fourteen genes encoding proteins of the light harvesting complex (Lhc) are
      expressed in a photoautotrophic cell culture from the wild species of tomato
      (Lycopersicon peruvianum). For two genes, Lhca2 (cab7) and Lhcb2(*)1 (cab4), a
      rhythmic oscillation of the transcript accumulation is observed under light/dark
      and constant dark conditions indicating that gene expression is controlled by a
      circadian clock in the tomato cell culture. The circadian expression of the Lhc
      genes remains present after application of 2,2'-dipyridyl. However, the amplitude
      of Lhc mRNA oscillations and the photosynthetic capacity (Fmax/Fo) decrease
      significantly. The transcript accumulations of psbA, rbcS and rbcL are less or
      not at all affected by 2,2'-dipyridyl. 

PMID- 24301710
TI  - Short-term responses of Photosystem I to heat stress : Induction of a PS II
      independent electron transport through PS I fed by stromal components.
AB  - When 23 degrees C-grown potato leaves (Solanum tuberosum L.) were exposed for 15
      min to elevated temperatures in weak light, a dramatic and preferential
      inactivation of Photosystem (PS) II was observed at temperatures higher than
      about 38 degrees C. In vivo photoacoustic measurements indicated that,
      concomitantly with the loss of PS II activity, heat stress induced a marked gas
      uptake activity both in far-red light (>715 nm) exciting only PS I and in
      broadband light (350-600 nm) exciting PS I and PS II. In view of its suppression
      by nitrogen gas and oxygen and its stimulation by high carbon-dioxide
      concentrations, the bulk of the photoacoustically measured gas uptake by heat
      stressed leaves was ascribed to rapid carbon-dioxide solubilization in response
      to light-modulated stroma alkalization coupled to PS I-driven electron transport.
      Heat-induced gas uptake was observed to be insensitive to the PS II inhibitor
      diuron, sensitive to the plastocyanin inhibitor HgCl2 and saturated at a rather
      high photon flux density of around 1200 MUE m(-2) s(-1). Upon transition from far
      red light to darkness, the oxidized reaction center P700(+) of PS I was re
      reduced very slowly in control leaves (with a half time t1/2 higher than 500 ms),
      as measured by leaf absorbance changes at around 820 nm. Heat stress caused a
      spectacular acceleration of the postillumination P700(+) reduction, with t1/2
      falling to a value lower than 50 ms (after leaf exposure to 48 degrees C). The
      decreased t1/2 was sensitive to HgCl2 and insensitive to diuron, methyl viologen
      (an electron acceptor of PS I competing with the endogenous acceptor ferredoxin)
      and anaerobiosis. This acceleration of the P700(+) reduction was very rapidly
      induced by heat treatment (within less than 5 min) and persisted even after
      prolonged irradiation of the leaves with far-red light. After heat stress, the
      plastoquinone pool exhibited reduction in darkness as indicated by the increase
      in the apparent Fo level of chlorophyll fluorescence which could be quenched by
      far-red light. Application (for 1 min) of far-red light to heat-pretreated leaves
      also induced a reversible quenching of the maximal fluorescence level Fm,
      suggesting formation of a pH gradient in far-red light. Taken together, the
      presented data indicate that PS I responded to the heat-induced loss of PS II
      photochemical activity by catalyzing an electron flow from stromal reductants.
      Heat-stress-induced PS I electron transport independent of PS II seems to
      constitute a protective mechanism since block of this electron pathway in
      anaerobiosis was observed to result in a dramatic photoinactivation of PS I. 

PMID- 24301711
TI  - Evidence of singlet oxygen evolution by whole living cells of Chlamydomonas
      reinhardtii.
AB  - The oxygen evolved by Chlamydomonas reinhardtii in the light is measured
      simultaneously with a Clark electrode and with the nitrosodimethylaniline
      imidazole colorimetric method which is specific for singlet oxygen. Experiments
      with wild-type and FuD7 mutant cells (unable to synthesize the D1 protein of
      Photosystem II), with dichlorophenyldimethylurea (which blocks electron transfer
      from Photosystem II to Photosystem I) and with dibromothymoquinone (which diverts
      electrons from their normal path between the two photosystems), as well as with
      hydroxylamine (an inactivator of the water-splitting part of Photosystem II and a
      competitor of water for electron donation to it), all point to the dependence of
      detected singlet oxygen on photolysis of water by Photosystem II. 

PMID- 24301712
TI  - Measurement of chlorophyll fluorescence within leaves using a modified PAM
      Fluorometer with a fiber-optic microprobe.
AB  - By using a fiber-optic microprobe in combination with a modified PAM Fluorometer,
      chlorophyll fluorescence yield was measured within leaves with spatial resolution
      of approximately 20 MUm. The new system employs a miniature photomultiplier for
      detection of the pulse-modulated fluorescence signal received by the 20 MUm fiber
      tip. The obtained signal/noise ratio qualifies for recordings of fluorescence
      induction kinetics (Kautsky effect), fluorescence quenching by the saturation
      pulse method and determination of quantum yield of energy conversion at
      Photosystem II at different sites within a leaf. Examples of the system
      performance and of practical applications are given. It is demonstrated that the
      fluorescence rise kinetics are distinctly faster when chloroplasts within the
      spongy mesophyll are illuminated as compared to palisade chloroplasts.
      Photoinhibition is shown to affect primarily the quantum yield of the palisade
      chloroplasts when excessive illumination is applied from the adaxial leaf side.
      The new system is envisaged to be used in combination with light measurements
      within leaves for an assessment of the specific contributions of different leaf
      regions to overall photosynthetic activity and for an integrative modelling of
      leaf photosynthesis. 

PMID- 24301713
TI  - Analysis of glycerophospho- and sphingolipids by CE.
AB  - Glycerophospholipids are amphiphilic molecules possessing polar head groups with
      a glycerol backbone and nonpolar variable long-chain fatty acids. Numerous
      molecular species are found in a single class of glycerophospholipid, conferring
      to these lipids a high structural diversity. They are major components of
      biological membranes and participate in important activities involving cell
      signaling and substrate transport. Sphingolipids consist of long-chain bases
      linked by an amide bond to a fatty acid and via the terminal hydroxyl group to
      complex carbohydrate or phosphorus moieties, constituting a complex family of
      compounds that also present an enormous structural variability. As important
      component of neuronal membranes, sphingolipids contribute to cellular diversity
      and functions and are associated with several neurodegenerative disorders.
      Moreover, they were studied in several foods due to their sensorial, reological,
      and antioxidant characteristics. In this work, the most relevant information
      available on glycerophospholipid and sphingolipid analysis by CE is reviewed. CE
      is a very promising analytical technique in polar lipid analysis, which provides
      high efficiency, relatively high resolution, and enormous versatility and
      requires small amounts of sample and solvent. MEKC and NACE methodologies have
      been developed as the most useful alternatives for these analyses by CE. Very
      interesting LODs have been achieved enabling the application of CE to the
      determination of glycerophospholipids and sphingolipids in several food and
      biological matrices. 

PMID- 24301714
TI  - 15-minute consultation: a structured approach to the assessment of chest pain in
      a child.
AB  - This article aims to provide a concise, structured approach to the child with
      chest pain. Chest pain is a common presenting symptom in children but, unlike in
      adults, the cause is rarely cardiac. We review the main causes of chest pain in
      children and discuss the important features that may alert those assessing
      paediatric chest pain to serious underlying pathology. In the vast majority of
      cases, reassurance is all that is required and a thorough initial consultation
      can exclude rare, serious disease and provide vital reassurance to children and
      families. 

PMID- 24301715
TI  - COVARIANCE SHRINKING IN ACTIVE SHAPE MODELS WITH APPLICATION TO GYRAL LABELING OF
      THE CEREBRAL CORTEX.
AB  - Active shape models (ASMs) have been widely used in segmentation tasks in medical
      image analysis. Complex structures and a limited number of training samples can,
      however, result in the failure to capture the complete range of shape variations.
      Various modifications to the point distribution model (PDM) have been proposed to
      increase the flexibility of the model. Still model parameters are often
      determined empirically without respect to the underlying data structure. We
      explore shrinkage covariance estimation in building a PDM by combining the sample
      covariance matrix with a target covariance matrix estimated from a low
      dimensional constrained model. Instead of using a global shrinkage intensity, we
      apply a spatially varying shrinkage intensity field to better adapt to the
      spatially varying characteristic of a complex shape. The parameters of the
      constrained model and the amount of shrinkage are determined in a data-driven
      fashion, so that the resulting distribution is optimized in representing the
      underlying data. The PDM, which we call SC-PDM, shows an increased flexibility in
      fitting new shapes and at the same time, is robust to noise. We demonstrate the
      effectiveness of using SC-PDM to label gyral regions on the human cerebral
      cortex.

PMID- 24301716
TI  - Payment systems and incentives in primary care: implications of recent reforms in
      Estonia and Romania.
AB  - Since the early 1990s, major reform in healthcare has been adopted in former
      communist countries in Central and Eastern Europe. More than 20 years after,
      reform in healthcare still draws much interest from policy makers and academics
      alike. One of the dynamic components of reform has been the reform of payment
      systems in primary care. This article looks at recent developments in payment
      systems and financial incentives in Estonia and Romania. We conclude that finding
      the appropriate mix in paying and incentivizing primary care providers in a
      transitional context is no easy solution for healthcare policy makers who need to
      carefully weigh in the advantages and inherent problems of various payment
      arrangements. In a transitional, rapidly changing healthcare system and society,
      and a context of financial stringency, the theoretical effects of payment
      mechanisms may be more difficult to predict and manage than it is expected.

PMID- 24301717
TI  - The manipulation of polar head group composition of phospholipids in the wheat
      Miranovskaja 808 affects frost tolerance.
AB  - Caryopses of the frost-resistant cultivar of the wheat Triticum aestivum L.,
      Miranovskaja 808, were germinated and grown in the presence of various
      concentrations of choline chloride. Changes in the composition of leaf total
      phospholipids and leaf total fatty acids at two extreme temperatures (25 degrees
      C and 2 degrees C) as well as changes in frost resistance were followed. A
      choline chloride concentration-dependent accumulation of phosphatidyl choline was
      observed in the leaves. Seedlings grown at 2 degrees C accumulated more
      phosphatidyl choline at each choline chloride concentration than those grown at
      25 degrees C. There was an inverse relationship between the contents of
      phosphatidyl choline and phosphatidic acid in the leaves. Neither the temperature
      nor choline chloride seemed to affect fatty-acid composition. Modification of
      polar-head group composition of phospholipids affected frost tolerance: Seedlings
      grown in the presence of 15 mM choline chloride at 25 degrees C exhibited a
      freezing resistance equal to that of hardened controls. The data indicate that
      the polar-head group composition of membrane phospholipids in plants can be
      easily manipulated and point to the importance of phosphatidyl choline in cold
      adaptation processes. 

PMID- 24301718
TI  - The ontogeny of lipid bodies (spherosomes) in plant cells : Ultrastructural
      evidence.
AB  - Maturing embryos of 16 oil plants, anise suspension culture cells, and Neurospora
      crassa cells were prepared for electron microscopy at different stages during
      massive lipid accumulation. Lipid-rich structures of certain species were best
      preserved by dehydration of fixed tissues in ethanol without propylene oxide,
      embedding in Spurr's Medium, and polymerization at room temperature. In all cells
      examined, spherical lipid bodies (spherosomes) showed a moderately osmiophilic,
      amorphous matrix and displayed a delimiting half-unit membrane when sectioned
      medially. Associations with the endoplasmic reticulum (ER) were viewed at any
      stage during lipid body development but with different frequency in the different
      plant species. Plastids of fat-storing cells exhibited conspicuously undulate
      outer and inner envelope membranes that formed multiple contact sites with each
      other and protuberances into both cytoplasm and stroma. Some species, e.g.,
      Linum, have plastids with tubular structures that connect the inner membrane to
      the thylakoid system; in addition, in the stroma vesicles fusing with or
      apparently passing through the envelope were observed. The outer envelope
      membrane may be associated with ER-like cytoplasmic membrane structures. In
      addition, lipid bodies of various sizes were found in contact with the plastid
      envelope. The ultrastructural observations are interpreted to match the published
      biochemical evidence, indicating that both plastids and ER may be involved in the
      synthesis of storage lipids and lipid body production. 

PMID- 24301719
TI  - Biochemical properties of potato phosphorylase change with its intracellular
      localization as revealed by immunological methods.
AB  - Phosphorylase was purified from young and senescent potato tubers. Antibodies
      raised against the enzyme from young tubers crossreacted with phosphorylase from
      old tissue, although the latter exhibited different physico-chemical properties.
      In polyacrylamide gel electrophoresis it migrated with higher mobility, its
      subunit molecular weight was determined in the range of 40,000 in contrast to
      100,000 of the phosphorylase in young tubers. The enzyme of senescent tubers
      displayed an isoelectric point of 5.4 different from the one of young tubers with
      5.0, and the diffusion coefficients of the two enzymes varied. The appearance of
      the phosphorylase form typical for senescent tissue is connected with changes in
      the intracellular localization as revealed by immunofluorescence. Before massive
      starch accumulation is initiated, non-vacuolated subepidermal cells contain
      antigenically active material in their cytoplasm. During starch accumulation in
      fully differentiated storage parenchyma, only amyloplasts fluoresce, indicating
      the presence of adsorbed phosphorylase protein. Cytoplasmic phosphorylase can be
      detected in the continuance of senescence and, finally, after 16 months of tuber
      storage, the particle-bound enzyme had mostly disappeared. Simultaneously, we
      observed membrane destruction and decomposition on the ultrastructural level. The
      phosphorylase from senescent potatoes is a converted molecule and seems to be
      formed by proteolytic cleavage. The location of phosphorylase in the amyloplasts
      during starch synthesis indicates that it also plays a role in starch synthesis
      and not only in its degradation. 

PMID- 24301720
TI  - High irradiance response promotion of a subsequent light induction response in
      Sinapis alba L.
AB  - Relative quantum responsivity curves for inhibition of hypocotyl elongation in
      Sinapis alba L. seedlings previously grown in white light confirm that a marked
      "end of day" inhibition response can be induced by a monochromatic light
      treatment (30 min) at the end of the light period. In dark grown seedlings,
      however, no growth inhibition can be induced by a 30 min monochromatic light
      treatment. A prerequisite for an induction response appears to be a pretreatment
      with continuous light. Far red light is most effective with blue and red light
      showing a lesser effectiveness. The light pretreatment also shows a marked
      fluence rate dependency with respect to its ability to allow an induction
      response to manifest itself. The pretreatment required shows all the
      characteristics of a classical "HIR" response. The appearance of the effect in
      plants treated with the herbicide SAN 9789 seems to exclude chlorophyll as being
      the photoreceptor. 

PMID- 24301721
TI  - Uptake of isolated plant chromosomes by plant protoplasts.
AB  - For mass isolation of plant metaphase chromosomes, cultured cells of wheat
      (Triticum monococcum) and parsley (Petroselinum hortense) were synchronized by
      hydroxyurea and colchicine treatment. This synchronization procedure resulted in
      high mitotic synchrony, especially in suspension cultures of parsley in which 80%
      of the cells were found to be at the metaphase stage. Mitotic protoplasts
      isolated from these synchronized cell cultures served as a source for isolation
      of chromosomes. The described isolation and purification method yielded
      relatively pure chromosome suspension. The uptake of the isolated plant
      chromosomes into recipient wheat, parsley, and maize protoplasts was induced by
      polyethylene-glycol treatment. Cytological studies provided evidences for uptake
      of plant chromosomes into plant protoplasts. 

PMID- 24301722
TI  - Differential growth of georeacting maize roots.
AB  - The growth rate of the two sides of 10-mm apical segments prepared from primary
      roots and of intact primary roots of maize has been analyzed in both vertical and
      horizontal positions, using a filming method allowing continuous growth
      recording. The data showed that the georeaction began by a decrease in the
      overall elongation rate of the roots. This inhibition is effective on the lower
      side of the bending zone, where the growth is practically stopped during the
      period of maximum rate of geocurvature. In contrast, the growth is slightly
      enhanced on the upper part of the elongating zone. 

PMID- 24301723
TI  - Metabolism of hydroxylamine by spinach leaf discs and its relationship to nitrate
      reduction.
AB  - Nitrate reduction in vivo by spinach leaf discs was shown to be inhibited by
      hydroxylamine when this was included in the nitrate reductase assay solutions or
      introduced to the tissue during a preincubation period. The sensitivity of
      nitrate reduction to hydroxylamine was not sufficient to suggest a natural
      process, considering the small endogenous concentrations of hydroxylamine in the
      leaves. Inhibition of nitrate reduction in vivo could be approximately related to
      rates of in vitro inhibition of nitrate reductase by this compound. There was no
      need to suppose conversion of hydroxylamine to cyanide to inhibit nitrate
      reduction. Some of the in vivo and in vitro characteristics of hydroxylamine
      inhibition of nitrate reductase are described. Hydroxylamine was metabolised by
      discs at rates comparable to nitrate reduction. Rates of metabolism of
      hydroxylamine, and its accumulation in the tissues from an external solution were
      both enhanced by light but little affected by anaerobiosis. 

PMID- 24301724
TI  - Evolution of enzymes involved in carbon metabolism (phosphoenolpyruvate and
      ribulose-bisphosphate carboxylases, phosphoenolpyruvate carboxykinase) during the
      light-induced greening of Euglena gracilis strains Z and ZR.
AB  - Phosphoenolpyruvate carboxykinase activity decreases when Euglena gracilis Z and
      ZR undergo light-induced chloroplast development in batch "resting" medium
      lacking utilizable organic carbon and CO2. This enzyme is present in
      heterotrophically grown cells (Briand et al. 1981) and assures gluconeogenesis.
      It was consistently more active in strain ZR. Decreased carboxykinase activities
      were accompanied by parallel increases in the activities of ribulose bisphosphate
      carboxylase and phosphoenolpyruvate carboxylase. The rates of O2 evolution in
      light were much lower than those of CO2 fixed simultaneously. The incorporation
      of (14)CO2 into early C-4 dicarboxylic acids was higher in green cells than in
      etiolated cells, and it was even higher in green cells assayed in light in the
      presence of (DCMU). A hypothesis has been proposed, according to which there is a
      possible cooperation of phosphoenolpyruvate carboxylase in photosynthetic CO2
      fixation, especially under conditions of limiting CO2.High temperatures (34
      degrees  C) depress carboxylation enzyme activities to a greater extent than that
      of the carboxykinase without a great effect on cellular chlorophyll content. In
      the presence of 25 MUm DCMU, however, chlorophyll accumulation is reduced without
      any detectable changes in enzyme activities in the Z strain. The ZR strain
      displayed its characteristic resistance to DCMU. 

PMID- 24301725
TI  - Evolution of carboxylating enzymes involved in paramylon synthesis
      (phosphoenolpyruvate carboxylase and carboxykinase) in heterotrophically grown
      Euglena gracilis.
AB  - Heterotrophically grown Euglena synthesize grains of paramylon, its reserve
      carbohydrate, in a vesicular complex of mitochondrial origin. A CO2 fixation
      activity in dark grown Euglena was demonstrated in the mitochondria via
      paramylon. At the beginning of the exponential phase of growth, the activity of
      phosphoenolpyruvate carboxykinase increases before the augmentation of
      paramylon.At the end of the exponential phase, the activity of this enzyme
      decreases, and low residual levels persist in the transition and stationary
      phases of growth. The activity of phosphoenolpyruvate carboxylase evolves
      inversely during the heterotrophic growth of the algae in succinate- or a lactate
      containing medium. A compartmentalized scheme of carbon metabolism in
      mitochondria is presented. 

PMID- 24301726
TI  - Cereal beta-amylase: Immunochemical study on two enzyme-deficient inbred lines of
      rye.
AB  - Two inbred lines of rye (Secale cereale L), the kernels of which displayed a very
      low level of beta-amylase activity (1-3% of the levels generally found in rye),
      were investigated in comparison with a third normal line. An anti-wheat beta
      amylase immune serum which cross-reacted with the rye enzyme was used in this
      study.The anti-wheat beta-amylase immune serum absorbed the beta-amylase activity
      in the three lines which were investigated. Comparably small amounts of enzymatic
      antigen corresponded to the small levels of activity detected in the enzyme
      deficient lines. The three inbred lines were equally able to germinate. One of
      the enzyme-deficient lines was further investigated and neither the level of
      activity nor the amount of enzymatic antigen were notably changed upon
      germination.The results indicate that the reduced activity is due neither to the
      presence of an inhibitor nor to the production of inactive enzymes. Germination
      can proceed normally without late production of beta-amylase. 

PMID- 24301727
TI  - Structural differentiation of membranes involved in the secretion of
      polysaccharide slime by root cap cells of cress (Lepidium sativum L.).
AB  - The peripheral secretion tissue of the root cap of Lepidium sativum L. was
      investigated by electronmicroscopy and freeze-fracturing in order to study
      structural changes of membranes involved in the secretion process of
      polysaccharide slime. Exocytosis of slime-transporting vesicles occurs chiefly in
      the distal region of the anticlinal cell walls. The protoplasmic fracture face
      (PF) of the plasmalemma of this region is characterized by a high number of
      homogenously distributed intramembranous particles (IMPs) interrupted by areas
      nearly free of IMPs. Near such areas slime-transporting vesicles are found to be
      underlying the plasma membrane. It can be concluded that areas poor in particles
      are prospective sites for membrane fusion. During the formation of slime
      transporting vesicles, the number of IMPs undergoes a striking change in the PF
      of dictyosome membranes and their derivatives. It is high in dictyosome cisternae
      and remarkably lower in the budding region at the periphery of the cisternae.
      Slime-transporting vesicles are as poor in IMPs as the areas of the plasmalemma.
      Microvesicles rich in IMPs are observed in the surroundings of dictyosomes. The
      results indicate that in the plasmalemma and in membranes of the Golgi apparatus
      special classes of proteins - recognizable as IMPs - are displaced laterally into
      adjacent membrane regions. Since the exoplasmic fracture face (EF) of these
      membranes is principally poor in particles, it can be concluded that membrane
      fusion occurs in areas characterized by a high quantity of lipid molecules. It is
      obvious that the Golgi apparatus regulates the molecular composition of the
      plasma membrane by selection of specific membrane components. The drastic
      membrane transformation during the formation of slime-transporting vesicles in
      the Golgi apparatus causes the enrichment of dictyosome membranes by IMPs,
      whereas the plasma membrane probably is enriched by lipids. The structural
      differentiations in both the plasma membrane and in Golgi membranes are discussed
      in relation to membrane transformation, membrane flow, membrane fusion, and
      recycling of membrane constituents. 

PMID- 24301728
TI  - Qualitative and quantitative changes in mRNA of castor beans during the initial
      stages of germination.
AB  - The increase in extractable RNA during the initial germination stages of castor
      bean was measured, for both the embryonic axis and the storage endsperm. The
      extractable rRNA increased between 24 and 72 h after initial imbibition in the
      embryo and 48-72 h in the endosperm. The mRNA species present over the first 6
      days of germination were identified by the products from in vitro translation.
      The mRNA from dry seeds gave predominantly low molecular weight polypeptide
      products. Between 0.5 and 1 h of initial imbibition new mRNA species were
      detectable and the qualitative changes were largely complete by 8 h, some 16 h-40
      h before the detectable quantitative changes. Despite the large variations in
      enzyme activity occurring 48 h-192 h after imbibition, the mRNA species
      qualitatively varied very little, after this initial change, up to 144 h after
      imbibition. In the light of this large, early, qualitative change in mRNA, the
      possible importance of long-lived mRNA in seed germination is discussed. 

PMID- 24301729
TI  - Subcellular localization of acid proteinase in barley mesophyll protoplasts.
AB  - Chloroplasts prepared from lysed protoplasts of barley mesophyll contain 2-8% of
      the total acid proteinase activity. This residual activity is not associated with
      intact chloroplasts isolated by means of density gradient centrifugation.
      Vacuoles isolated from lysed protoplasts contain 80-85% of the total acid
      proteinase activity, indicating that the enzyme(s) which is presumably
      responsible for the degradation of chloroplastic proteins is located largely in
      the central vacuoles of mesophyll cells. 

PMID- 24301730
TI  - An aqueous pomegranate seed extract ameliorates oxidative stress of human
      hepatoma HepG2 cells.
AB  - BACKGROUND: Aqueous pomegranate seed extract (PSE), a by-product of the
      pomegranate juice industry, was recently identified as a potential antiglycative
      ingredient. Ellagic acid was proposed as the major polyphenol responsible for the
      antiglycative activity as exerted in in vitro models. However, there is no
      information on safety aspects of this extract in biological systems before its
      application as ingredient. The cytotoxicity of PSE (1-100 ug mL(-1) ) was
      evaluated by determining its effect on cell viability and redox status of
      cultured HepG2 cells. The protective effect of the PSE against oxidative stress
      induced by tert-butyl hydroperoxide (t-BOOH) was also investigated. RESULTS: No
      changes in cell integrity or intrinsic antioxidant status resulted from a direct
      treatment with aqueous PSE, even at high dosage. In addition, reactive oxygen
      species (ROS) induced by t-BOOH were reduced by 21% when cells were pretreated
      with 100 ug mL(-1) of aqueous PSE at 180 min. The range of concentrations
      investigated was effective in decreasing the ROS formation but not in a dose
      dependent manner. CONCLUSION: Aqueous pomegranate seed extract enhances human
      hepatoma cells integrity and resistance to cope with a stressful situation at
      concentration up to 100 ug mL(-1) .

PMID- 24301731
TI  - A radio-education intervention to improve maternal knowledge of obstetric danger
      signs.
AB  - OBJECTIVE: To examine whether a radio-education intervention (REI) is associated
      with improved maternal knowledge of pregnancy danger signs (PDS) in Nicaragua.
      METHODS: This cross-sectional pilot study used pretests and posttests to evaluate
      whether an REI was associated with improved knowledge of PDS among 77 pregnant
      and postpartum women in Nicaragua. RESULTS: The total number of PDS identified by
      study participants increased from 130 before the intervention to 200 after the
      intervention, an increase of 53.8% (Wilcoxon signed-rank test (z) = -4.18; P <
      0.00001). The three PDS for which participant knowledge increased significantly
      after the intervention were 1) swelling of the face and hands, 2) convulsions,
      and 3) vaginal bleeding. Participants who 1) reported having a sister who had
      experienced a pregnancy complication, 2) lived in an urban setting, and 3) had
      more than a sixth-grade education were significantly more likely to score higher
      on posttests related to knowledge of PDS than those without those attributes
      (90.9% versus 56.9% [Chi2 (degrees of freedom) = 4.60 (1); P = 0.043; n = 76];
      75% versus 45.9% [Chi2 = 6.8 (1); P = 0.009; n = 77]; and 62.5% (12+ years
      education) versus 79.3% (6-12 years) versus 50.0% (0-6 years education) versus
      25.0% (no education) [Chi2 = 8.11 (1); P = 0.044; n = 77] respectively).
      CONCLUSIONS: Exposure to the REI was associated with a significant increase in
      the ability to identify PDS. Further studies should establish whether this
      increase in knowledge of PDS is associated with increases in use of maternity
      care services and decreases in delays in seeking care.

PMID- 24301732
TI  - [Impact assessment of the rotavirus vaccine in Colombia using rapid evaluation
      methods].
AB  - OBJECTIVE: Estimate the effectiveness of the monovalent rotavirus vaccine in
      preventing the need to hospitalize children under 2 years old for acute diarrheal
      disease in five Colombian cities. METHODS: A population survey was conducted
      based on a probability sample of children over 2 months and under 24 months of
      age in five Colombian cities (Barranquilla, Bogota, Cali, Cartagena, and
      Riohacha) over the period from August through October 2010. The vaccine had been
      introduced in the Expanded Program on Immunization in January 2009. Rotavirus
      vaccination coverage was estimated by age group; the cumulative incidence of
      hospitalization for severe diarrhea was determined; and the magnitude of
      correlation between vaccination with one or two doses of rotavirus vaccine and
      hospitalization for diarrhea was calculated using the age-adjusted probability
      ratio (PR) and other epidemiologically significant factors. Effectiveness of the
      vaccine was estimated using the expression 1-PR. RESULTS: Coverage with a single
      dose of the rotavirus vaccine was 87.3%. During the 12 months prior to the
      survey, 1 453 of the children under 24 months old in the study areas (43.2%) had
      presented with diarrhea, and of these, 174 (5.2%) had been hospitalized for this
      cause. The effectiveness of two doses of the vaccine in preventing
      hospitalization for severe diarrhea was 68% (CI 95% = 55%-77%). CONCLUSIONS: In
      Colombia, rotavirus vaccination protects against hospitalization for diarrhea due
      to any cause. The use of cross-sectional surveys appeared to be adequate for
      rapid evaluation of an immunization program's effectiveness with a new vaccine.

PMID- 24301733
TI  - [Contribution of hospitalizations for primary care-sensitive conditions to the
      profile of admissions in the public health care system].
AB  - OBJECTIVE: To describe the epidemiological profile of hospitalizations in the
      city of Divinopolis, state of Minas Gerais, Brazil, to estimate the prevalence of
      hospitalizations for primary care-sensitive conditions (HPCSC), and to evaluate
      the factors associated with the occurrence of HPCSC. METHODS: A cross-sectional
      study was conducted of the two public health care institutions in Divinopolis
      qualified to hospitalize individuals; that is, a general hospital and an urgent
      care unit. The data were collected between July and October 2011. Admissions were
      screened based on information available through the state of Minas Gerais data
      exchange software SUS Facil, hospital admission authorizations, and patient
      records. Descriptive analyses were carried out, with estimation of the prevalence
      of admissions according to the groups of the 10th revision of the International
      Classification of Diseases (ICD-10). The identification and classification of
      HPCSC was based on the Brazilian List of primary-care sensitive conditions
      published by the Ministry of Health. The strength of the association between
      HPCSC and selected variables was estimated based on the prevalence ratio.
      RESULTS: Two thousand seven hundred seventy five admissions were identified. The
      main causes were neoplasms (18%), diseases of the circulatory system (16%),
      pregnancy and childbirth (15%), and external causes (12%). The prevalence of
      HPCSC was 36.6%, with the main diagnoses being diseases of the circulatory and
      respiratory systems. One third of the admissions occurred through the urgent care
      unit, which was also responsible for more than half of the HPCSC. Female sex, age
      younger than 13 years and older than 40 years, and living in Divinopolis were
      associated with higher chance of admission due to HPCSC (P < 0.01). CONCLUSIONS:
      The results show a high prevalence of HPCSC, especially through the urgent care
      unit. This indicates an overburdening of urgent care services, hindering the
      implementation of a longitudinal continuum of care at the primary level.

PMID- 24301734
TI  - Obesity and malnutrition among Hispanic children in the United States: double
      burden on health inequities.
AB  - OBJECTIVE: To examine important micronutrient deficiencies related to child
      health and growth outcomes for all weight statuses to 1) better understand other
      potential nutritional problems and inequities that may be masked by focusing
      solely on BMI percentiles and overweight/obesity, and 2) draw attention to the
      need for more studies focused on the nutritional well-being of children at all
      weight statuses, including healthy weight. METHODS: A sample of children (ages 2
      19 years) old from the National Health and Nutrition Examination Survey (NHANES)
      2003-2010 was analyzed. Prevalence of stunting, folate, vitamin D, iron, iodine,
      and anemia, was considered. Comparisons were conducted between non-Hispanic
      whites and Hispanics, and within Hispanics, based on socio-demographic and
      economic characteristics. RESULTS: Hispanic children experienced significantly
      higher prevalence of stunting (6.1% versus 2.6%), and the prevalence of stunted
      Hispanic children in the healthy weight category was higher than those in the
      overweight/obese category. Comparable percentages were observed by ethnicity for
      most analyzed micronutrients, although girls had consistently higher prevalence
      of nutritional deficiencies than boys, especially girls reaching reproductive
      age. CONCLUSIONS: The results of this article draw attention to the need for more
      specific and differentiated analyses of child obesity and nutritional status
      among and within ethnic, sex, and age groups. Appropriate public health
      interventions need to consider the entire range of weight statuses and
      micronutrient deficiencies to eliminate inequities among minority children,
      especially girls.

PMID- 24301735
TI  - [Validation of Code Red: a proposal for the treatment of obstetric hemorrhage].
AB  - OBJECTIVE: Evaluate the effect of scenario-based simulation training and
      management guidelines on the prevention and treatment of obstetric hemorrhage.
      METHODS: This quasi-experimental before-and-after study measured the effect of an
      intervention that used simulation scenarios, together with the delivery of
      reminders as part of the strategy, to train health workers in the recognition and
      treatment of obstetric hemorrhage. The intervention consisted of two one-day
      training sessions conducted six months apart. The effect on patient management
      was evaluated by reviewing the patients' clinical histories 24 months before and
      18 months after the intervention. RESULTS: In tests administered to the group of
      health workers who received the training, their median grade increased from 55%
      correct answers before the training to 85% afterwards (P < 0,001). Before the
      training, there were 124 cases of hemorrhage (2.1%), whereas after the
      intervention the incidence fell to 86 (1.8%), representing a 16.5% decline (RR =
      0.84; CI 95% = 0.6-1.1). The use of oxytocin increased from 58.3% to 74.1% (RR =
      3; CI 95% = 1.0-1.6) and active monitoring during the immediate -puerperium rose
      from 5% to 36.5% (RR = 4; CI 95%: 3.0-18.1). CONCLUSIONS: The intervention
      increased the use of beneficial practices for the prevention and early detection
      of hemorrhage, resulting in an improvement in the incidence of hemorrhage,
      although it was not statistically significant. It is essential to use simulation
      training on a regular basis, together with additional strategies adapted to local
      conditions and the circumstances of the particular group.

PMID- 24301736
TI  - Influence of context in social participation of people with disabilities in
      Brazil.
AB  - OBJECTIVE: To identify environmental and personal factors associated with social
      participation in adults with various diseases/health conditions residing in the
      urban areas of the Belo Horizonte Metropolitan Region, Minas Gerais, Brazil.
      METHODS: Individual characteristics, social participation, and perception of
      environmental barriers of 226 patients treated at a public rehabilitation
      referral service were evaluated. Regression analyses with hierarchical entry of
      data were performed to verify the association of personal and environmental
      factors with social participation. RESULTS: More years of schooling, being
      engaged in the labor market, and consuming alcohol are conditions that increase
      the social participation of patients. Natural environment, transportation, access
      to health services, and social capital are perceived as the most important
      barriers to participation. Based on the linear regression analysis, the adjusted
      coefficient (R2(adj)) of the full model was 0.42 (P = 0.000). CONCLUSIONS: The
      results of this study may contribute to the planning and implementation of
      interventions and public policies at the individual and contextual level that are
      considered appropriate for reducing barriers and facilitate full participation.

PMID- 24301737
TI  - [Effective interventions in the problematic use of alcohol and other drugs].
AB  - OBJECTIVE: Synthesize and assess the available scientific evidence from the
      period 2008-2012 on interventions of demonstrated efficacy in the treatment and
      rehabilitation of adolescents and adults engaged in the problematic use of
      alcohol and other substances. METHODS: A systematic review was undertaken with
      search and analysis of national and international literature on the subject in
      Spanish and English in the main international databases: PubMed/MEDLINE, LILACS,
      Embase, PsycINFO, SciELO, the databases of the York University Centre for Reviews
      and Dissemination (DARE, ETS Database), the Cochrane Library, and other sources
      of gray literature. The search criteria included randomized clinical trials and
      systematic reviews but excluded observational studies, qualitative studies, and
      articles of poor methodological quality. RESULTS: The final sample consisted of
      69 studies. The psychosocial interventions shown to be effective were cognitive
      behavioral therapy, family interventions, self-help interventions using the
      Internet, couples behavioral therapy, community strengthening and family
      training, telephone monitoring and support, and integrated therapy for substance
      abuse disorder with anxiety and depression comorbidity. Pharmacological
      interventions of demonstrated effectiveness were acamprosate, lysergic acid
      diethylamide (LSD), and benzodiazepines in problematic alcohol use, as well as
      maintenance therapy with high-dose opioids. CONCLUSIONS: The demonstrated
      effectiveness of psychosocial and pharmacological interventions is slight but
      significant. However, strongly multidisciplinary interventions that use a
      cognitive behavioral approach and the involvement of people close to the
      consumer, as well as some of the specific pharmacological interventions, have
      been shown to yield the best results in terms of indicators of abstinence and
      prevention of relapses.

PMID- 24301738
TI  - A systematic review of alcohol use and sexual risk-taking in Latin America.
AB  - OBJECTIVE: To provide an account of published literature on the association
      between alcohol use and sexual risk-taking, focusing on Latin America. METHODS: A
      search of MEDLINE, Embase, Web of Science, LILACS, and Cochrane databases
      identified 561 unique articles. After excluding those that were not directly
      relevant, 30 studies were retained for review. RESULTS: Twenty-seven studies
      showed direct or indirect associations between alcohol abuse and
      unprotected/risky sex. Three studies, however, showed no association between
      these variables, suggesting that the public health message of safer sex may have
      been effective. CONCLUSIONS: Further research is needed to identify factors and
      behaviors that could be modified to reduce the association between alcohol use
      disorders and risky sexual behavior.

PMID- 24301739
TI  - Viral hepatitis in Latin America and the Caribbean: a public health challenge.
AB  - Viral hepatitis (VH) is an emergent concern in public health agendas worldwide.
      More than one million people die annually from hepatitis and 57% and 78% of
      global cirrhosis and hepatocellular carcinoma cases, respectively, are caused by
      VH. The burden of disease caused by hepatitis in Latin America and the Caribbean
      (LAC) is high. Data on hepatitis has been collected in several countries, but
      more accurate and comparable studies are needed. Hepatitis B vaccination and
      screening of donated blood are routine practices in the region. However,
      integrated policies covering prevention and control of disease caused by all
      types of hepatitis viruses are scarce. Existing preventive measures need to be
      reinforced. Attention must be paid to at-risk populations, awareness campaigns,
      and water and food safety. Affordable access to diagnosis and treatment,
      population screening, referral to health services and monitoring of positive
      cases are among the main challenges currently posed by VH in LAC. The World
      Health Organization framework and Pan American Health Organization regional
      strategy, defined in response to resolution WHA63.18 of the World Health
      Assembly, may help to overcome these difficulties. Successful experiences in the
      fight against hepatitis in some LAC countries may also provide very interesting
      solutions for the region. 

PMID- 24301740
TI  - Spot versus overnight urine as an alternative for 24-hour urine collection to
      assess sodium intake.

PMID- 24301741
TI  - Spot and overnight urine are inappropriate to assess population sodium intake.

PMID- 24301742
TI  - [Eliminating tuberculosis one neighborhood at a time].
AB  - OBJECTIVES: We evaluated a strategy for preventing tuberculosis (TB) in
      communities most affected by it. METHODS: In 1996, we mapped reported TB cases
      (1985-1995) and positive tuberculin skin test (TST) reactors (1993-1995) in Smith
      County, Texas. We delineated the 2 largest, densest clusters, identifying 2
      highest-incidence neighborhoods (180 square blocks, 3153 residents). After
      extensive community preparation, trained health care workers went door-to-door
      offering TST to all residents unless contraindicated. TST-positive individuals
      were escorted to a mobile clinic for radiography, clinical evaluation, and
      isoniazid preventive treatment (IPT) as indicated. To assess long-term impact, we
      mapped all TB cases in Smith County during the equivalent time period after the
      project. RESULTS: Of 2258 eligible individuals, 1291 (57.1%) were tested, 229
      (17.7%) were TST positive, and 147 were treated. From 1996 to 2006, there were no
      TB cases in either project neighborhood, in contrast with the preintervention
      decade and the continued occurrence of TB in the rest of Smith County.
      CONCLUSIONS: Targeting high-incidence neighborhoods for active, community-based
      screening and IPT may hasten TB elimination in the United States.

PMID- 24301743
TI  - DNA elimination in embryogenic development of Pennisetum glaucum x Pennisetum
      purpureum (Poaceae) hybrids.
AB  - Interspecific hybridization between Napier grass (Pennisetum purpureum), which is
      widely grown in Brazil for cattle forage, and pearl millet (Pennisetum glaucum)
      has been used as a breeding strategy for the development of improved cultivars.
      However, the hybrid between these two species is sterile due to its triploid
      condition (2n = 3x = 21 chromosomes), which hinders its use in crop breeding
      programs. It is known that genomic alterations result from the hybridization
      process. In order to measure the loss of DNA during embryo development, we used
      flow cytometry to estimate the nuclear DNA content of triploid and tetraploid
      embryos produced by interspecific hybridization between Napier grass and pearl
      millet. The triploid and tetraploid hybrids had a mean DNA content of 4.99-4.87
      and 5.25-4.84 pg, at 10 and 30 days after pollination, respectively. The mean
      reduction in DNA content was higher in the tetraploid hybrids. The flow cytometry
      results revealed progressive genomic instability in these triploid and tetraploid
      hybrids, with this instability causing significant alterations in the DNA content
      of the hybrids. 

PMID- 24301744
TI  - Molecular authentication of multi-species honeysuckle tablets.
AB  - Authenticating multi-species original raw materials in commercial formulations is
      difficult. Jin Yin Hua and Shan Yin Hua, both classified as raw honeysuckle
      materials in the Chinese Pharmacopoeia, are used in various medicines.
      Differentiating one variety from another is difficult based on chemical analysis.
      We developed molecular authentication of multi-species original honeysuckle in 3
      brands of commercial tablets using allele-specific PCR. All 3 tablets contained
      both Jin Yin Hua and Shan Yin Hua. We also built a PCR-enzyme digestion method
      and enzymatic mutation detection in the PCR fragments of psbA-trnH and trnL-trnF,
      and the restriction endonucleases HinfI and NlaIV, respectively. The PCR-enzyme
      digestion method produced the same result as the allele-specific PCR. Sequence
      and phylogenetic analyses show that the tablets YXC and YQJ contained Lonicera
      japonica and L. macranthoides as original raw materials, and LYG contained L.
      japonica, L. hypoglauca, and L. macranthoides. 

PMID- 24301745
TI  - A duplex SYBR Green I real-time quantitative PCR assay for detecting Escherichia
      coli O157:H7.
AB  - PCR and hybridization assays are widely used for the detection and identification
      of Escherichia coli serogroups and serotypes. We used these techniques for the
      detection of E. coli O157:H7, a dominant serogroup among E. coli strains that are
      considered major public health problems worldwide. We developed a quantitative
      PCR assay using SYBR Green I, based on the published sequences of the rfbE and
      fliC genes from E. coli O157:H7. This method detected the E. coli O157:H7 O
      somatic antigen gene and the flagellar antigen gene simultaneously, with good
      specificity, sensitivity, and repeatability. The sensitivity of the assay was
      2.95 x 10 copies/uL, which is 10(3) times more sensitive than obtained with a
      conventional PCR. The intra-assay and inter-assay coefficients of variation were
      less than 2%. We concluded that this duplex quantitative PCR assay is adequate
      for the identification and quantitative analysis of E. coli O157:H7. This
      provides a new identification method for clinical diagnosis of E. coli O157:H7
      and for food safety analysis, as well as for molecular epidemiological studies of
      foodborne diseases. 

PMID- 24301746
TI  - Rapid method for DNA extraction from the honey bee Apis mellifera and the
      parasitic bee mite Varroa destructor using lysis buffer and proteinase K.
AB  - We developed a rapid method for extraction of DNA from honey bees, Apis
      mellifera, and from the parasitic bee mite, Varroa destructor. The advantages
      include fast processing and low toxicity of the substances that are utilized. We
      used lysis buffer with nonionic detergents to lyse cell walls and proteinase K to
      digest proteins. We tested whole thorax, thoracic muscle mass, legs, and antennae
      from individual bees; the mites were processed whole (1 mite/sample). Each thorax
      was incubated whole, without cutting, because exocuticle color pigment darkened
      the extraction solution, interfering with PCR results. The procedure was
      performed with autoclaved equipment and laboratory gloves. For each sample, we
      used 100 uL lysis buffer (2 mL stock solution of 0.5 M Tris/HCl, pH 8.5, 10 mL
      stock solution of 2 M KCl, 500 uL solution of 1 M MgCl2, 2 mL NP40, and 27.6 g
      sucrose, completed to 200 mL with bidistilled water and autoclaved) and 2 uL
      proteinase K (10 mg/mL in bidistilled water previously autoclaved, as proteinase
      K cannot be autoclaved). Tissues were incubated in the solutions for 1-2 h in a
      water bath (62 degrees -68  degrees C) or overnight at 37  degrees C. After
      incubation, the tissues were removed from the extraction solution (lysis buffer +
      proteinase K) and the solution heated to 92  degrees C for 10 min, for proteinase
      K inactivation. Then, the solution with the extracted DNA was stored in a
      refrigerator (4 degrees -8  degrees C) or a freezer (-20  degrees C). This method
      does not require centrifugation or phenol/chloroform extraction. The reduced
      number of steps allowed us to sample many individuals/day. Whole mites and bee
      antennae were the most rapidly processed. All bee tissues gave the same quality
      DNA. This method, even using a single bee antenna or a single mite, was adequate
      for extraction and analysis of bee genomic and mitochondrial DNA and mite genomic
      DNA.

PMID- 24301747
TI  - Proteomic response of Moniliophthora perniciosa exposed to pathogenesis-related
      protein-10 from Theobroma cacao.
AB  - TcPR-10, a member of the pathogenesis-related protein 10 family, was identified
      in EST library of interactions between Theobroma cacao and Moniliophthora
      perniciosa. TcPR-10 has been shown to have antifungal and ribonuclease activities
      in vitro. This study aimed to identify proteins that are differentially expressed
      in M. perniciosa in response to TcPR-10 through a proteomic analysis. The fungal
      hyphae were subjected to one of four treatments: control treatment or 30-, 60- or
      120-min treatment with the TcPR-10 protein. Two-dimensional maps revealed 191
      differentially expressed proteins, 55 of which were identified by mass
      spectrometry. The proteins identified in all treatments were divided into the
      following classes: cell metabolism, stress response, zinc binding,
      phosphorylation mechanism, transport, autophagy, DNA repair, and oxidoreductases.
      The predominant class was stress-response proteins (29%), such as heat shock
      proteins; these proteins exhibited the highest expression levels relative to the
      control treatment and are known to trigger defense mechanisms against cytotoxic
      drugs as well as TcPR-10. Oxidoreductases (25%) were overexpressed in the control
      and in 30-min treatments but exhibited reduced expression at 120 min. These
      proteins are involved in the repair of damage caused by oxidative stress due to
      the contact with TcPR- 10. Consistent with the antifungal activity of TcPR-10,
      several proteins identified were related to detoxification, autophagy or were
      involved in mechanisms for maintaining fungal homeostasis, such as ergosterol
      biosynthesis. These results show that the sensitivity of the fungus to TcPR-10
      involves several biochemical routes, clarifying the possible modes of action of
      this antifungal protein. 

PMID- 24301748
TI  - Molecular typing of Yersinia pseudotuberculosis strains isolated from livestock
      in Brazil.
AB  - Yersinia pseudotuberculosis can infect a broad range of animals. In Brazil, this
      bacterium has been isolated from healthy and sick animals from sporadic cases and
      outbreaks of hemorrhagic gastroenteritis among livestock. However, the molecular
      diversity of these isolates is little understood. In this study, we used
      multilocus sequence typing, enterobacterial repetitive intergenic consensus PCR
      and pulsed-field gel electrophoresis to genotype 40 Y. pseudotuberculosis strains
      belonging to bio-serogroups 1/O:1a and 2/O:3 isolated between 1982 and 1990 in
      the southern region of Brazil. All three methodologies clustered the strains into
      two main clusters according to their bio-serogroups. Good correlations were
      observed between the clusters and the pathogenic potential of the strains. No
      correlation among the strains was observed according to geographical origin,
      host, place, or year of isolation. The grouping of the Y. pseudotuberculosis
      isolated in Brazil determined by these assays leads us to suggest that Brazilian
      livestock harbor two subpopulations of Y. pseudotuberculosis. 

PMID- 24301749
TI  - Cytogenetic and anatomic behavior of cytochimeras and total polyploids in
      cassava.
AB  - Cassava periclinal cytochimeras, cultivars, and interspecific hybrid and
      polyploid types were studied in relation to embryonic, cytogenetic, and
      anatomical behavior. Their apical shoots, pollen grains, male and female buds,
      roots, stomata, and flowering period were analyzed. Chimeras exhibited increased
      size of L1 and L2 cells. Polyploidy led to enlargement of stomata in chimeras
      whereas L2 gave tetraploid chromosome configurations, tetrad irregularity,
      decrease of pollen viability, and increase in frequency of polyembryo sacs. The
      chimeric composition of tetraploids L1 and L2 and diploid L3 expressed a notable
      epigenetic effect seen in a marked enlargement of edible roots compared to total
      diploid. One of the chimeric types was accompanied by complete flowering
      inhibition. Pollen viability and diameter appeared to be reliable markers to
      determine ploidy levels. 

PMID- 24301750
TI  - Proteins differentially expressed by Shiga toxin-producing Escherichia coli
      strain M03 due to the biliar salt sodium deoxycholate.
AB  - Shiga toxin-producing Escherichia coli (STEC) can cause conditions ranging from
      diarrhea to potentially fatal hemolytic uremic syndrome. Enteropathogen
      adaptation to the intestinal environment is necessary for the development of
      infection, and response to bile is an essential characteristic. We evaluated the
      response of STEC strain M03 to the bile salt sodium deoxycholate through
      proteomic analysis. Cell extracts of strain M03 grown with and without sodium
      deoxycholate were analyzed by two-dimensional electrophoresis; the differentially
      expressed proteins were identified using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Three proteins were found
      to be differentially expressed due to sodium deoxycholate. Glycerol dehydrogenase
      and phosphate acetyltransferase, which are involved in carbon metabolism and have
      been associated with virulence in some bacteria, were downregulated. The
      elongation factor Tu (TufA) was upregulated. This protein participates in the
      translation process and also has chaperone activities. These findings help us
      understand strategies for bacterial survival under these conditions. 

PMID- 24301751
TI  - Clinical value of surfactant protein-A in serum and sputum for pulmonary
      tuberculosis diagnosis.
AB  - The aim of this study was to explore the diagnostic and differential diagnosis
      value of surfactant protein-A (SP-A) in the serum and sputum for pulmonary
      tuberculosis. A total of 101 patients with pulmonary tuberculosis, 85 healthy
      volunteers, and 30 chronic obstructive pulmonary disease (COPD) patients were
      divided into pulmonary tuberculosis group, healthy control group, and COPD group,
      respectively. SP-A was determined in the serum and sputum in the three groups by
      enzyme-linked immunosorbent assay. The expression of SP-A in serum was
      significantly higher (P < 0.05) in the pulmonary tuberculosis group than in the
      healthy control and COPD groups. There were no differences in the SP-A expression
      in the sputum among the three groups. There was no significant effect of gender,
      age, tubercle bacillus antibodies, tuberculin purified protein derivative trial,
      leukocyte count, neutrophilic granulocyte, lymphocyte percentage, or lung
      cavities on SP-A levels in serum or sputum for the pulmonary tuberculosis group
      (P > 0.05). The detection of SP-A in serum and sputum was shown to be of great
      value for the diagnosis and differential diagnosis of pulmonary tuberculosis, and
      therefore merits further investigation. 

PMID- 24301752
TI  - BDNF Val66Met polymorphism and serum concentrations of BDNF with smoking in Thai
      males.
AB  - Many studies have suggested that brain-derived neurotrophic factor (BDNF) is
      involved in the reward system of addiction, and that nicotine may induce
      alterations in BDNF gene expression and its protein level within the
      mesocorticolimbic system. We investigated the BDNF levels and biochemical
      hematological parameters of smoker and non-smoker groups, and examined the
      association of the Val66Met BDNF gene polymorphism with BDNF serum levels and
      cigarette smoking. The study sample comprised 311 Thai volunteers (200 smokers;
      111 non-smokers). The levels of serum BDNF and biochemical-hematological
      parameters were determined. The Val66Met BDNF polymorphism was genotyped by the
      polymerase chain reaction-restriction fragment length polymorphism technique. The
      smoker group had significantly higher serum BDNF levels than the non-smoker group
      (8.3 vs 6.5 ng/mL, P < 0.05). BDNF concentrations correlated positively with
      hemoglobin, hematocrit, red blood cell count, white blood cell count, platelet
      count, number of cigarettes smoked, and thiocyanate level (P < 0.05). No
      association was found between the BDNF Val66Met genotype and the serum BDNF
      level. The BDNF Val66Met polymorphism was not significantly associated with the
      smoking status of the Thai males in this study. Cigarette smoking may be one
      factor that determines the serum BDNF level, but the BDNF Val66Met polymorphism
      probably does not influence susceptibility to smoking among Thai males. 

PMID- 24301754
TI  - Spermatogenesis in Triatoma melanocephala (Hemiptera: Triatominae).
AB  - Triatoma melanocephala is a rare species of Hemiptera. It belonged to the
      Brasiliensis subcomplex and presents morphological characteristics very close to
      those of Triatoma vitticeps. We investigated spermatogenesis of T. melanocephala
      and compared it with that of T. vitticeps in order to determine whether these
      organisms have similar cytogenetic characteristics. Lacto-acetic orcein staining
      was used to observe all stages of meiosis. These two species were found to have
      the same karyotype (2n = 20A + X1X2X3Y), heteropycnotic corpuscles in the
      polyploid spermatogonial cells, interfasic and profasic nucleus, and chromocenter
      with four sex chromosomes during prophase. Thus, we conclude that besides the
      morphologic similarity of T. melanocephala with T. vitticeps, they also have
      similar spermatogenesis and cytogenetics. 

PMID- 24301753
TI  - Expression profile analysis reveals putative prostate cancer-related microRNAs.
AB  - Annotation of prostate cancer (PC) genomes provides a foundation for discoveries
      that can improve the understanding and treatment of the disease. Therefore, in
      the present study, we used the Student t-test to identify differentially
      expressed PC-related mRNAs and microRNAs (miRNAs). Then, we performed
      interrelated mapping of miRNA target genes between abnormally expressed mRNAs and
      miRNAs, and explored mRNA-target miRNA interrelated pairs to explain the
      biological functions of miRNA during the progression of PC, thus revealing the
      occurrence of miRNA-mediated PC. After Gene Set Functional Similarity analysis,
      we obtained 20 abnormal PC-related candidate miRNAs, including hsa-miR-26a, hsa
      miR-152, hsa-miR-19a, hsa-miR-30c, hsa-miR-19b, and hsa-miR-146b-5p, among
      others. These results suggest that it may be possible to predict the clinical
      behavior of prostate cancer based on gene expression analysis. 

PMID- 24301755
TI  - Microsporogenesis in Paspalum conspersum Schrad. (Virgata group) with different
      ploidy levels.
AB  - Knowledge about the cytology and reproductive behavior of a species is
      indispensable for hybridization programs. This is especially true for species
      belonging to the genus Paspalum, among which apomixis and a wide range of ploidy
      levels are frequently found. Paspalum conspersum Schrad. is a robust and warm
      season perennial bunchgrass native to South America. Previous studies have
      indicated that both tetraploid and hexaploid races exist in this species;
      however, only information related to tetraploids has been applied to another
      taxon. In this study, a cytological investigation in two Brazilian accessions
      collected in different regions revealed tetraploidy in the accession BRA-012823
      (2n = 4x = 40), with chromosome pairing in bivalents and normal meiosis and
      tetrad formation, and pentaploidy (2n = 5x = 50) in the accession BRA-022748,
      which presented total asynapsis. In this latter accession, 50 univalents could be
      scored at diakinesis. After alignment at the metaphase plate, sister chromatids
      segregated to the poles. Only one meiotic division (equational) occurred, and
      after cytokinesis, 100% of the dyads that formed had 2n microspores. The meiotic
      behavior during microsporogenesis, which showed 10 delayed univalents to reach
      the metaphase plate, suggests that this accession is a recent natural hybrid
      constituted by a parental genome with 40 chromosomes and another with 10
      chromosomes. The potential usage of these accessions in Paspalum breeding has
      been discussed. 

PMID- 24301756
TI  - A preliminary mutation analysis of phenylketonuria in southwest Iran.
AB  - Phenylketonuria (PKU) is a heterogeneous and autosomal recessive metabolic
      disorder that is mainly caused by mutations in the hepatic phenylalanine
      hydroxylase (PAH) gene. This study was designed to identify PAH mutations within
      exons 6, 7, and 10-12 in PKU patients from southwest Iran. Forty Iranian patients
      with clinical and biochemically confirmed PKU were enrolled. The exons were
      sequenced directly and 13 different mutations were identified including I224T,
      S231P, R176X, c.592_613del22, R243X, R252W, R261Q, Y356X, V388M, IVS10-11G>A,
      IVS11+1G>C, IVS11-2A>G, and Q375R, which were associated with 23 genotypes. A
      novel sequence variant, Q375R (c.1124A>G), was detected in exon 11. In one
      patient, a typical genotype with more than two mutations (R243X/S231P/S231P) was
      found. Seven different polymorphisms and three new variants were also detected in
      intron regions of PAH. A high mutation spectrum was predicted in the southwestern
      region of Iran due to its ethnic heterogeneity, especially the Khuzestan
      Province. The detection of 13 different mutations, corresponding to a mutation
      detection rate of 53.75%, confirmed this phenomenon. 

PMID- 24301757
TI  - Analysis of BCR/ABL transcripts in healthy individuals.
AB  - The chimeric oncogene BCR/ABL, which is the product of reciprocal translocation
      between chromosomes 9 and 22, is a known molecular marker of chronic myeloid
      leukemia (CML), and is related to the major factors involved in leukemogenesis.
      Some previous studies have also reported the presence of this oncogene in
      peripheral blood cells of healthy individuals. In this study, we investigated the
      presence of BCR/ABL transcripts in peripheral blood of individuals aged 40 years
      or more without symptoms of CML. The presence of BCR/ABL transcripts was observed
      in 2 of the 30 individuals analyzed. The genesis of BCR/ABL transcripts and its
      presence in healthy individuals are topics of ongoing debate. The risks and
      biological implications of the presence of BCR/ABL transcripts in healthy
      individuals are challenging issues that remain to be elucidated. 

PMID- 24301758
TI  - Male infertility in Northeast China: molecular detection of Y chromosome
      microdeletions in azoospermic patients with Klinefelter's syndrome.
AB  - The prevalence of microdeletions of azoospermia factor (AZF) among azoospermic
      Klinefelter's syndrome (KFS) patients shows conflicting data. We aimed to detect
      this frequency in a Northeast Chinese population, and to investigate the possible
      association between AZF microdeletions and KFS by comparison with previous
      conflicting reports. Eighty men affected with KFS and a random healthy control
      group comprising 60 fertile men and women were recruited. AZF microdeletions were
      detected by multiplex polymerase chain reaction using 9 specific sequence-tagged
      sites. Karyotype analyses were performed on peripheral blood lymphocytes using
      standard G-banding. Finally, azoospermia was confirmed in 77 men affected with
      KFS and no AZF microdeletions were found. Karyotype analysis revealed 1 patient
      with karyotype 47,XXY,inv (9) (p11, q13), and 2 with mosaic karyotypes
      (46,XX/47,XXY and 46,XY/47,XXY). All other patients had karyotype 47,XXY. Review
      of the literature showed that these results were similar to those of other
      regions of Northeast Asia, but differed from those obtained from Caucasian
      populations. Our results supported the proposal that AZF microdeletions and KFS
      result from separate genetic defects. The prevalence of AZF in azoospermic KFS
      patients varies among populations, and it might result from genetic drift or
      selective pressure. These results suggest that routine screening for classical
      AZF microdeletions among infertile azoospermic men with a 47,XXY karyotype might
      not be necessary in Northeast Chinese individuals. However, it remains imperative
      for patients considering assisted reproductive treatments, particularly for those
      with mosaic karyotypes. 

PMID- 24301759
TI  - Association of -238G/A and -863C/A polymorphisms in the TNF-alpha gene with
      chronic obstructive pulmonary disease based on a meta-analysis.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory
      disease; increasing evidence indicates that the TNF-alpha polymorphism is
      associated with progression of this disease. Few studies have focused upon
      association between TNF-alpha -238G/A or -863C/A polymorphism and COPD risk.
      Reported associations have been controversial because of small sample size and
      varied study design among the different studies. We performed a meta-analysis to
      assess the correlation of these two polymorphisms in the TNF-alpha gene with COPD
      risk. A comprehensive search was conducted to identify all published articles on
      the association between TNF-alpha -238G/A or -863C/A polymorphism and COPD risk
      from different databases. Pooled odds ratios (ORs) with 95% confidence intervals
      (CI) were calculated, and the heterogeneity and publication bias were assessed.
      Eight articles with 10 eligible studies met our inclusion criteria; six studies
      were of the -238G/A polymorphism and the others involved the -863C/A
      polymorphism. In the case of the -863C/A polymorphism, significant association
      was detected only in Asians in the A allele carriers (GA+AA versus GG genotype)
      and allele (A versus G allele) model (OR = 0.505, 95%CI = 0.321-0.795 and OR =
      0.560, 95%CI = 0.368-0.851, respectively). However, no significant association
      was detected for the -238G/A polymorphism. No evidence of between-study
      heterogeneity and publication bias was detected. We suggest a potentially
      protective role of the A allele in the TNF-alpha -863C/ A polymorphism against
      developing COPD in Asians. This hypothesis needs further studies for
      confirmation. 

PMID- 24301760
TI  - Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid
      carcinoma using multiplex allele-specific polymerase chain reaction combined with
      denaturing high-performance liquid chromatography.
AB  - Mutations in the V-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) play
      an important role in the pathogenesis of papillary thyroid cancer (PTC). In this
      study, a BRAF V600E mutation was detected in formalin-fixed and paraffin-embedded
      PTC samples using multiplex allele-specific polymerase chain reaction and
      denaturing high-performance liquid chromatography. The sensitivity of the assays
      was validated in two cell lines, K1 and RO82-W-1, which were respectively
      positive and negative for the mutation. The method enabled detection of very low
      concentrations (~1%) of the mutation, with positive findings obtained in 119 of
      the 187 samples (63.6%). The mutation was not detected in 20 cases of benign
      thyroid diseases. The presence of the mutation was significantly associated with
      ages >45 years, the tumor-nodes-metastasis stage, region of metastasis, and
      clinical outcome (P < 0.05). Although no correlation was found between the
      mutation and lymph node metastasis, the proportions of patients carrying a
      mutation differed significantly between central and lateral cervical lymph node
      metastasis (P < 0.05). Multivariate logistic regression analysis also indicated
      the presence of mutation, tumor size, and cervical lymph node metastasis to be
      independent predictors for recurrence and distant metastasis. We conclude that a
      high proportion of PTC cases likely harbors the BRAF V600E mutation. This
      mutation can be used as an independent factor for predicting the recurrence and
      distal metastasis of PTC tumors. 

PMID- 24301761
TI  - Genetic diversity in natural populations of Theobroma subincanum Mart. in the
      Brazilian Amazon.
AB  - The genus Theobroma, recently reclassified in the family Malvaceae, comprises
      some species with high economic potential, including the cupui, Theobroma
      subincanum Mart., which has not yet been domesticated, and whose genetics and
      population structure are mostly unknown. This study aimed to assess the
      population structure and genetic diversity in natural populations of T.
      subincanum Mart., using inter-simple sequence repeat (ISSR) markers. A total of
      59 individuals were sampled in three geographically separate populations, CFA,
      CMN, and CPT. Nei's genetic distance was estimated to characterize populations
      with the use of 13 polymorphic primers. The analysis of molecular variance
      revealed that the variability between populations (51.71%) was higher than that
      within populations (48.29%). Among the three populations, CPT showed the highest
      diversity index and percentage of polymorphism. The ISSR molecular markers were
      efficient and presented sufficient polymorphism to estimate genetic diversity in
      populations of T. subincanum Mart. 

PMID- 24301762
TI  - Prevalence of diabetes and impaired fasting glucose in Uygur children of
      Xinjiang, China.
AB  - This study was designed to estimate the prevalence of diabetes and impaired
      fasting glucose (IFG) in Xinjiang children in western China. Data were obtained
      from the Chun-Miao Project, a community-based, cross-sectional study designed to
      investigate the prevalence and risk factors of diabetes in children of the
      Chinese Uygur population in Xinjiang from February 2010 to May 2012. A total of
      3644 children completed the survey and measurements of fasting glucose. Diabetes
      and IFG were defined using American Diabetes Association 2009 criteria. Overall,
      0.7% of the 3644 Uygur children had IFG and 0.1% had diabetes. In the newborn to
      8-year-old group, the prevalence of diabetes and IFG was 0.6 and 1.1%,
      respectively. In the 9-13-year-old group, the prevalence of diabetes and IFG was
      0.1 and 0.7%, respectively. There was no evidence of IFG or diabetes in the 14-17
      year-old group. Logistic regression analysis suggested that overweight and
      obesity were independent risk factors of diabetes in Uygur children of Xinjiang.
      The prevalence of diabetes and IFG in Uygur children was lower than that reported
      previously in children of other ethnicities in China. 

PMID- 24301763
TI  - Lack of genotoxicity in Astyanax bimaculatus and Oreochromis niloticus of 17alpha
      methyltestosterone used in fish hatcheries to produce male monosex populations.
AB  - 17alpha-Methyltestosterone (MT) is widely used in fish hatcheries of many
      countries to produce male monosex populations. Its genotoxic risk to fish species
      is not well known and studies in other in vivo models are still inconclusive. MT
      was tested for genotoxicity in the fish species Oreochromis niloticus (tilapia),
      a target species, and Astyanax bimaculatus (lambari), a native non-target
      species. Genotoxicity was evaluated by the micronucleus test (MN), nuclear
      abnormalities (NA), and comet assay using peripheral erythrocytes of both species
      after a 96-h exposure to MT at concentrations of 0.01, 0.1, and 1.0 mg/L in the
      water. At the lowest exposure level of 0.01 mg/L, MT induced MN in both species
      and NA only in O. niloticus. These effects were not observed in the comet assay.
      Chromatographic analysis of water samples collected from aquariums at the
      beginning and end of each experiment showed that MT was consumed during the 96-h
      exposure. At the highest level of exposure (1.0 mg/L), 81.69% of the hormone was
      consumed during the exposure period. The chromatogram showed that at the lowest
      concentration level of 0.01 mg/L, 99.56% MT was consumed by the end of the
      exposure period. Thus, exposure to MT did not cause genotoxicity in either fish
      species. 

PMID- 24301765
TI  - Stigma receptivity, mode of reproduction, and mating system in Mesosetum chaseae
      Luces (Poaceae), a native grass of the Brazilian Pantanal.
AB  - Mesosetum chaseae Luces, known regionally as "grama-do-cerrado", is abundant in
      the Pantanal region in Brazil and contributes significantly to livestock and
      environmental conservation. This species is under basic studies at Embrapa
      Pantanal (Nhecolandia subregion, Pantanal, Corumba, MS, Brazil). In this study,
      we present data about stigma receptivity, mode of reproduction, and mating system
      for 10 accessions collected in Nhecolandia subregion (Pantanal). Stigma
      receptivity was optimal, producing innumerous oxygen bubbles upon testing with
      hydrogen peroxidase. Clarified ovaries analyzed under interference microscopy
      showed an embryo sac of the Polygonum type, typical of sexual species. The mating
      system, tested in protected flowers, indicated allogamy. These data are important
      for subsidizing future breeding programs for this species. 

PMID- 24301764
TI  - DNA-based and geometric morphometric analysis to validate species designation: a
      case study of the subterranean rodent Ctenomys bicolor.
AB  - The genus Ctenomys (Rodentia: Ctenomyidae) shows several taxonomic
      inconsistencies. In this study, we used an integrative approach including DNA
      sequences, karyotypes, and geometric morphometrics to evaluate the taxonomic
      validity of a nominal species, Ctenomys bicolor, which was described based on
      only one specimen in 1912 by Miranda Ribeiro, and since then neglected. We
      sampled near the type locality assigned to this species and collected 10
      specimens. A total of 820 base pairs of the cytochrome b gene were sequenced and
      analyzed together with nine other species and four morphotypes obtained from
      GenBank. Bayesian analyses showed that C. bicolor is monophyletic and related to
      the Bolivian-Matogrossense group, a clade that originated about 3 mya. We
      compared the cranial shape through morphometric geometrics of C. bicolor,
      including the specimen originally sampled in 1912, with other species
      representative of the same phylogenetic group (C. boliviensis and C. steinbachi).
      C. bicolor shows unique skull traits that distinguish it from all other currently
      known taxa. Our findings confirm that the specimen collected by Miranda Ribeiro
      is a valid species, and improve the knowledge about Ctenomys in the Amazon
      region. 

PMID- 24301766
TI  - Effects of glucose sensing/signaling on oxidative stress response in glucose
      repression mutants of Schizosaccharomyces pombe.
AB  - The resistant to glucose repression mutants of Schizosaccharomyces pombe (ird5,
      ird13, and ird14) have a high tolerance to oxidative stress induced by H2O2. In
      all ird mutants, the increased expression level of the fbp1 gene can be
      interpreted as a lack of glucose repression in these mutants. To investigate the
      mechanisms of the oxidative stress response in ird mutants, we analyzed the
      transcription of stress response-related genes, sod1, ctt1, atf1, pap1, and sty1,
      under stressed and non-stressed conditions. We then analyzed the phosphorylation
      state of the Sty1-MAP kinase in ird mutants. Our findings support the concept of
      an adaptive response to oxidative stress in these mutants. In addition, these
      results imply that either glucose signaling mechanisms leading to glucose
      repression and glucose utilization as an energy source are regulated apart from
      each other or, like Saccharomyces cerevisiae, S. pombe might have additional
      glucose detection systems. 

PMID- 24301767
TI  - Electrophoresis and spectrometric analyses of adaptation-related proteins in
      thermally stressed Chromobacterium violaceum.
AB  - Chromobacterium violaceum is a Gram-negative proteobacteria found in water and
      soil; it is widely distributed in tropical and subtropical regions, such as the
      Amazon rainforest. We examined protein expression changes that occur in C.
      violaceum at different growth temperatures using electrophoresis and mass
      spectrometry. The total number of spots detected was 1985; the number ranged from
      99 to 380 in each assay. The proteins that were identified spectrometrically were
      categorized as chaperones, proteins expressed exclusively under heat stress,
      enzymes involved in the respiratory and fermentation cycles, ribosomal proteins,
      and proteins related to transport and secretion. Controlling inverted repeat of
      chaperone expression and inverted repeat DNA binding sequences, as well as
      regions recognized by sigma factor 32, elements involved in the genetic
      regulation of the bacterial stress response, were identified in the promoter
      regions of several of the genes coding proteins, involved in the C. violaceum
      stress response. We found that 30  degrees C is the optimal growth temperature
      for C. violaceum, whereas 25, 35, and 40  degrees C are stressful temperatures
      that trigger the expression of chaperones, superoxide dismutase, a probable small
      heat shock protein, a probable phasing, ferrichrome-iron receptor protein,
      elongation factor P, and an ornithine carbamoyltransferase catabolite. This
      information improves our comprehension of the mechanisms involved in stress
      adaptation by C. violaceum.

PMID- 24301768
TI  - Molecular characterization by amplified ribosomal DNA restriction analysis and
      antimicrobial potential of endophytic fungi isolated from Luehea divaricata
      (Malvaceae) against plant pathogenic fungi and pathogenic bacteria.
AB  - Luehea divaricata is an important plant in popular medicine; it is used for its
      depurative, anti-inflammatory, and other therapeutic activities. We evaluated the
      antimicrobial activity of endophytic fungi isolated from leaves of L. divaricata
      against phytopathogens and pathogenic bacteria, and characterized the isolates
      based on amplified ribosomal DNA restriction analysis (ARDRA). The in vitro
      antagonistic activity of these endophytes against the phytopathogen Alternaria
      alternata was assayed by dual culture technique. Based on this evaluation of
      antimicrobial activity, we extracted secondary metabolites from nine endophytic
      fungi by partitioning in ethyl acetate and methanol. These were tested against
      the phytopathogens A. alternata, Colletotrichum sp and Moniliophthora perniciosa,
      and against the human pathogenic bacteria Escherichia coli and Staphylococcus
      aureus. Molecular characterization by ARDRA technique was used for phylogenetic
      analysis, based on comparison with sequences in GenBank. The endophytes had
      varied effects on A. alternata. One isolate produced an inhibition halo against
      M. perniciosa and against E. coli. This antibiosis activity indicates a role in
      the protection of the plant against microbial pathogens in nature, with potential
      for pharmaceutical and agricultural applications. Based on ARDRA, the 13 isolates
      were grouped. We found three different haplotypes of Phomopsis sp, showing
      interspecific variability. It appears that examination of the microbial community
      associated with medicinal plants of tropical regions has potential as a useful
      strategy to look for species with biotechnological applications. 

PMID- 24301769
TI  - Global comparison of gene expression between subcutaneous and intramuscular
      adipose tissue of mature Erhualian pig.
AB  - Adipose tissue plays an important role in energy metabolism and related diseases.
      The content of intramuscular fat significantly influences the pork quality. In
      this study, the whole gene expression of dorsal subcutaneous (s.c.) adipose
      tissue and intramuscular (i.m.) adipose tissue isolated from longissimus dorsi
      muscle tissue were compared using Affymetrix Gene-Chip microarray technology. The
      result revealed that 1228 genes were more highly expressed in s.c. adipose
      tissue, whereas 965 genes were higher expressed in i.m. adipose tissue. We found
      that the s.c. adipose tissue had a stronger capacity of lipid metabolism and
      fatty acid metabolism compared with i.m. adipose tissue, and angiopoietin-like-4,
      neuronatin, neuron-derived orphan receptor-1 alfa, and chloride intracellular
      channel 5 may play important roles in the regulation of fat deposition between
      i.m. and s.c. adipose tissues. 

PMID- 24301770
TI  - Comparative proteomic analysis between early developmental stages of the Coffea
      arabica fruits.
AB  - Coffee is one of the most valuable agricultural commodities. There is much
      agronomic research on coffee, but molecular knowledge of its fruit development
      and ripening is limited. This study reports a comparative proteomic investigation
      of immature coffee fruits in two early developmental stages: stage 1, cell
      division and elongation of the perisperm; and stage 2, early growth of the
      endosperm progressively replacing the perisperm. Proteins were extracted using a
      modified SDS-phenol method and two-dimensional electrophoresis gels stained with
      Coomassie blue revealed about 300 well-resolved polypeptide spots in the pH range
      of 3 to 10. The differentially expressed polypeptides spots were excised, trypsin
      digested, and analyzed by MALDI-TOF mass spectrometry. Peptide MS data were
      searched against the coffee EST database. Most of the identified protein spots
      are involved in the glycolytic pathway and energy reserve, and are more highly
      expressed at stage 2. 

PMID- 24301771
TI  - Identification of orchardgrass (Dactylis glomerata L.) cultivars by using simple
      sequence repeat markers.
AB  - The accurate identification of orchardgrass (Dactylis glomerata L.) cultivars is
      necessary to ensure purity for consumers, the effective utilization of cultivars,
      and to protect the intellectual property for breeders. Therefore, this study
      aimed to use SSR to construct DNA fingerprinting of orchardgrass cultivars. The
      genetic diversity of 32 orchardgrass cultivars originated from 21 countries, but
      grown in China, was assessed using a set of 29 SSR markers distributed across 9
      linkage groups of the orchardgrass genome. A total of 229 bands were detected,
      with an average of 7.9 bands per marker. The average polymorphic rate for the
      species was 92.1%. The polymorphism information content ranged from 0.771 to
      0.893. The genetic similarity ranged from 0.55 to 0.84, which confirmed a high
      level of genetic diversity among orchardgrass cultivars. The unweighted pair
      group method, in combination with the arithmetic mean algorithm (UPGMA)
      dendrogram and principal coordinate analysis, showed a separation of 6 major
      clusters among 32 cultivars. The number of distinguishable cultivars ranged from
      3 to 23, with an average of 12.1 per primer. Moreover, 11 bands that showed
      stable and repeatable SSR patterns were amplified by A01E14, A01K14, and D02K13.
      These bands were used to develop the DNA fingerprints for 32 orchardgrass
      cultivars. In the DNA fingerprints constructed, each cultivar had a unique
      fingerprinting pattern that was easily distinguished from the others. These
      results indicate that the SSR marker was polymorphic, and reliable for use in
      potential large-scale DNA fingerprinting of orchardgrass cultivars. 

PMID- 24301772
TI  - Genetic composition of a Brazilian population: the footprint of the Gold Cycle.
AB  - Ancestry-informative markers (AIMs) are powerful tools for inferring the genetic
      composition of admixed populations. In this study, we determined the genetic
      ancestry of the Ouro Preto (Brazil) population and evaluated the association
      between ancestry and self-reported skin color. The genetic ancestry of 189
      children and adolescents was estimated by genotyping 15 AIMs. The estimate of
      population admixture was determined using the Bayesian Markov Chain Monte Carlo
      (MCMC) method implemented in two different programs (STRUCTURE and ADMIXMAP).
      Volunteers self-reported their skin colors. The European ancestry contribution
      ranged from 0.503 to 0.539, the African contribution ranged from 0.333 to 0.425,
      and the Amerindian component ranged from 0.04 to 0.164. The relative
      contributions of African (P < 0.016) and European (P < 0.011) ancestry differed
      significantly among skin color groups, except between black and dark-brown
      groups. The population of Ouro Preto has a higher contribution of African
      ancestry compared to the mean for the southeast region of Brazil. Therefore,
      extrapolating the African ancestry contribution for southeastern Brazil to the
      Ouro Preto population would underestimate the actual value for this city. We also
      showed that self-reported skin color could be appropriate for describing the
      genetic structure of this particular population. 

PMID- 24301773
TI  - In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on
      human white blood cells exposed to methylmercury.
AB  - Environmental contamination by methylmercury (MeHg) is an enormous public health
      problem in world regions such as Amazonia. MeHg toxic effects seem to be
      influenced by environmental and genetic factors. However, few studies have
      evaluated the genetic influences of MeHg toxicity in humans. Therefore, the aim
      of this study was to evaluate the genetic influence of Ala16Val manganese
      superoxide dismutase gene polymorphism (Ala16Val-MnSOD) on the cytotoxic effects
      of in vitro human leukocytes exposed to MeHg. Subjects were selected from 100
      individuals aged 26.4 +/- 7.3 years genotyped to Ala16Val-MnSOD polymorphism (AA
      = 6, VV = 6, and AV = 12) to perform in vitro testing using white blood cells
      (WBCs). Reactive oxygen species production was measured using 2',7'
      dichlorofluorescein diacetate fluorimetric assay, and cell viability was measured
      using MTT assay on WBC samples from the same subjects that were both exposed and
      not exposed to MeHg (2.5 uM for 6 h). The results showed that AA- and VV-WBCs
      exposed to MeHg did not display increased reactive oxygen species levels compared
      to those in cells that were not exposed. However, AV-leukocytes exposed to MeHg
      displayed increased ROS levels. Cellular viability comparison among genotypes
      exposed to MeHg showed that the viability of AA-WBCs was lower than that of VV
      WBC, with mean values of 3.46 +/- 0.13 and 3.08 +/- 0.77 (standard error),
      respectively (P = 0.033), whereas heterozygous cells (AV) displayed intermediate
      values. This difference was likely due to the higher basal H2O2 production of AA
      WBCs compared to that of other genotypes. These results suggest that the Ala16Val
      MnSOD polymorphism has toxicogenetic effects in human cells exposed to MeHg. 

PMID- 24301774
TI  - Genetic variability in accessions of the acerola germplasm bank of Universidade
      Federal Rural de Pernambuco, Brazil.
AB  - Brazil is the world's largest producer of acerola, Malpighia emarginata
      (Malpighiaceae); the Northeast is responsible for 60% of the national production.
      The culture of acerola in Brazil has great genetic variability; plantings have
      high phenotypic diversity and are not very productive, often originating from
      propagation by seed. We evaluated the genetic diversity of 42 accessions from the
      Acerola Active Germplasm Bank of Universidade Federal de Pernambuco. Using 15
      RAPD primers, 182 markers were obtained, of which 166 were polymorphic and 16
      were monomorphic. We found high genetic variability among the accessions (HE =
      0.29), with no redundancy. Considering the accessions from the states of
      Pernambuco, Bahia and Para as distinct groups, there was greater diversity in
      accessions from Bahia than from the other two states. 

PMID- 24301775
TI  - Spectrum of mutations in the familial Mediterranean fever gene (MEFV) in Turkish
      patients of the Central Anatolia region: a comparison of two mutation detection
      system.
AB  - The purpose of this study was to determine the spectrum of the most common
      mutations in the familial Mediterranean fever gene (MEFV) in Turkish patients
      from the Central Anatolia region, by using two different methods for detecting
      FMF-associated mutations with different screening panels, and compare our results
      with other diagnostic molecular genetics centers. A total of 1579 patients were
      analyzed. Genomic DNA from 304 patients was tested for 6 common mutations located
      in exon 2 (E148Q), and exon 10 (M680I, M694V, M694I, V726A, R761H) by real-time
      PCR while 1275 patients were tested for 17 mutations located in exon 2 (E148Q),
      and exon10 [M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, S675N,
      G678E, M680L, T681I, M694L, K695M, R717S, I720M, V722M] by pyrosequencing. The
      most frequent mutation was M694V, followed by M680I, E148Q, and V726A. Ten
      mutations in the panel were not detected in any patients. Finally, we compared
      our results with those of other centers in Turkey to contribute to the identified
      spectrum of Turkish MEFV mutations and we discuss which MEFV mutations are
      informative for evaluating an FMF patient. 

PMID- 24301776
TI  - Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from
      Northeast China with different folate levels.
AB  - Hypomethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter in
      glioma cells has been associated with temozolomide resistance. S
      adenosylmethionine (SAM), which is produced during folate metabolism, is the main
      source of methyl groups during DNA methylation. As a key enzyme during folate
      metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may
      regulate folate end-products. We investigated the effect of typical polymorphisms
      of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate
      levels in patients with glioma from Northeast China. A total of 275 patients with
      glioma and 329 without malignant tumors were tested. Serum folate concentration
      was assayed by using the electrochemiluminescence immunoassay. MTHFR
      polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain
      reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The
      constituent ratio of glioma patients below the serum folate biological reference
      value was significantly higher than that of the control population (P < 0.001).
      In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C
      mutation were found in higher frequency than homozygotes or wild types
      (oligodendroglioma, P < 0.001; glioblastoma, P < 0.01). When grouped by the
      median or biological reference value of serum folate, only homozygotes for C677T
      with low levels of folate were significantly associated with decreased
      methylation of MGMT (median, P < 0.001; biological reference value, P = 0.036).
      These data suggest that, in combination with a negative folate balance in glioma
      patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.

PMID- 24301778
TI  - Association of paraoxonase polymorphisms with carotid artery atherosclerosis in
      essential hypertension patients.
AB  - We investigated the relationships between paraoxonase genetic polymorphisms and
      essential hypertension in carotid artery atherosclerotic patients. The study
      included 353 Han participants and 240 Uighur participants from Xinjiang; they
      were further divided into two groups: essential hypertension with carotid artery
      atherosclerosis (CAAD group) and essential hypertension without carotid artery
      atherosclerosis (control group). Genotypes were detected by PCR, followed by
      restriction analyses with specific endonucleases. In Han people, the M allele
      frequency was significantly higher in the CAAD group than in the control group.
      The CC/CS genotype and C allele frequencies were significantly higher in the CAAD
      group than in the control group. Logistic regression analysis demonstrated that
      PON1 55M allele [odds ratio (OR) = 1.889] and PON2 311C allele (OR = 1.692) are
      independent risk factors for CAAD. Combined genotype analysis showed that PON1
      55M and PON2 311C alleles are independent risk factors for CAAD (OR = 1.428). In
      the Uighur population, the CC/ CS genotype and C allele frequencies were
      significantly higher in the CAAD group than in the control group. Logistic
      regression analysis demonstrated that the PON2 311C allele is an independent risk
      factor for CAAD. We conclude that the PON1 55M and PON2 311C alleles are
      independent risk factors for CAAD in essential hypertension patients from the
      Xinjiang Han population. We also conclude that the PON2 311C allele is a risk
      factor for CAAD in essential hypertension patients from the Xinjiang Uighur
      population. 

PMID- 24301779
TI  - Isolation and identification of bovine primary hepatocytes.
AB  - The liver is a unique organ that is endowed with a plethora of specialized
      functions. Most of its functional traits are controlled by hepatocytes. Primary
      hepatocytes have been used widely in in vitro models to understand the biological
      processes occurring in the liver. There are a number of methods used to separate
      hepatocytes, but the cell activity and purity are much lower in this condition.
      On the basis of previous research, in this study, the two-step collagenase
      perfusion technique was used for isolating hepatocytes. The key proteins of
      hepatocytes, cytokeratin-18 (CK-18) and albumin (ALB), were used to identify
      cells, and their contents were evaluated by immunohistochemistry and Western
      blotting. The results showed that the isolated hepatocytes comprised more than
      96% of the corresponding protein volume stability. Therefore, this method was
      demonstrated to be reliable for identifying hepatocytes. 

PMID- 24301780
TI  - MicroRNA expression profiling studies on bronchopulmonary dysplasia: a systematic
      review and meta-analysis.
AB  - Over the past several years, several microRNA (miRNA) expression profiling
      studies have been carried out on bronchopulmonary dysplasia (BPD) in mammalian
      lung tissues. The most effective way to identify these important miRNAs is to
      systematically search for similar signatures identified in multiple independent
      studies. Accordingly, a meta-analysis was conducted to review published miRNA
      expression profiling studies that compared miRNA expression profiles between BPD
      lung tissues and normal lung tissues. A vote-counting strategy that considered
      the total number of studies and time points reporting differential expression was
      applied. Furthermore, cut-off criteria of statistically significant
      differentially expressed miRNAs as defined by the author and their predicted
      target genes, if available, as well as the list of up- and down-regulated miRNA
      features, were collected and recorded. Results of the meta-analysis revealed that
      four up-regulated miRNAs (miRNA-21, miRNA-34a, miRNA-431, and Let-7f) and one
      down-regulated miRNA (miRNA-335) were differentially expressed in BPD lung
      tissues compared with normal groups. In addition, eight miRNAs (miRNA-146b, miRNA
      29a, miRNA-503, miRNA-411, miRNA-214, miRNA-130b, miRNA-382, and miRNA-181a-1*)
      were found to show differential expression not only in the process of normal lung
      development, but also during the progress of BPD. Finally, several meaningful
      target genes (such as the HPGD and NTRK genes) of common miRNAs (such as miRNA-21
      and miRNA-141) were systematically predicted. These specific miRNAs may provide
      clues of the potential mechanisms involved in BPD. Further mechanistic and
      external validation studies are needed to confirm the clinical significance of
      these miRNAs in the development of BPD. 

PMID- 24301781
TI  - Analysis of mitochondrial DNA using amplified fragment length polymorphism
      markers of isonuclear allocytoplasmic male sterile wheat accessions and their
      maintainer lines.
AB  - To produce a good F1 hybrid variety wheat crop, it is necessary to explore novel
      cytoplasmic male sterility (CMS) lines and their maintainer line. This study
      aimed to identify cytoplasmic variation in three isonuclear-alloplasmic male
      sterile lines Aegilops kotschyi (Ae.kots) -90-110, Aegilops ventricosa (Ae.ven) 
      90-110, and Triticum spelta (T.spelta) -90-110 and their maintainer line, A-90
      110, at the molecular level. Mitochondrial DNA (mtDNA) was isolated using a
      combination of centrifugation and density gradient ultracentrifugation, sucrose
      sedimentation, lysis with sodium dodecyl sulfate (SDS), potassium proteinase, and
      phenol/chloroform extraction methods. To detect mtDNA purity, specific primers
      were designed for nuclear (beta-actin) and mitochondrial (COXIII) genes. Results
      indicated that the mtDNA was pure, and therefore suitable for polymerase chain
      reaction (PCR) and genetic analysis. Comparative analysis of mtDNA was conducted
      using amplified fragment length polymorphism (AFLP) markers. Reproducible
      polymorphisms were detected between the Aegilops and Triticum species and the
      male sterile lines. Four specific primers were screened from 64 AFLP marker
      primers, which provided the molecular basis for further studies investigating
      specific cytoplasmic male sterility characteristics. 

PMID- 24301782
TI  - Molecular characterization of cathepsin L cDNA and its expression during
      oogenesis and embryogenesis in the oriental river prawn Macrobrachium nipponense
      (Palaemonidae).
AB  - We identified the cDNA sequence of cathepsin L (CatL) in Macrobrachium
      nipponense, designated as MnCatL, for the first time. The MnCatL cDNA, isolated
      from the ovary, was 1710 bp in length, containing a 31-bp 5'-untranslated region,
      a 650-bp 3'-untranslated region, and an open reading frame of 1029 bp, encoding a
      342-amino acid polypeptide with a predicted molecular mass of 37.7 kDa. The
      polypeptide is composed of an 18-amino acid signal peptide, a 106-amino acid
      propeptide and a 218-amino acid mature peptide. MnCatL mRNA was detected in all
      tissues that we examined, including the thoracic ganglia, heart, muscle,
      intestine, hemocytes, ovary, testis, gills, and hepatopancreas. MnCatL expression
      reached a maximum value in both hepatopancreas and ovaries at the later stages of
      vitellogenesis, suggesting that MnCatL is involved in ovarian maturation of the
      oriental river prawn. During embryogenesis, MnCatL expression decreased as the
      embryo developed. The expression of MnCatL in the ovary and embryo suggest that
      MnCatL plays an important role in the uptake of vitellogenin and yolk protein,
      which are deposited in the oocyte for ovary maturation and embryo development,
      during oogenesis and embryogenesis of M. nipponense. 

PMID- 24301783
TI  - Development of 1047 insertion-deletion markers for rice genetic studies and
      breeding.
AB  - In this study, a total of 1047 insertion-deletion (InDel) primer pairs
      distributed across the rice genome were developed and experimentally validated.
      The primer pairs were designed based on the InDel length polymorphisms between 93
      11 (Oryza sativa ssp indica cv.) and Nipponbare (Oryza sativa ssp japonica cv.),
      aiming for utilization between indica and japonica rice, or between other inter
      subspecific rice cultivars. The 1047 primer pairs were dispersed across all 12 of
      the rice chromosomes, with one InDel marker found every 371.3 kb on average. The
      InDel length of the markers varied from 3 to 39 bp: 88.2% of the markers
      contained 6 to 25 bp, only 6.2% of markers were <= 5 bp, and 5.6% were >= 26 bp.
      Six hundred and twenty-three (59.5%) of the 1047 InDel markers were shown to
      amplify well and were polymorphic between Taichung65 and IR8, and 476 (45.5%)
      markers were polymorphic between Lemont and Yangdao4, while 398 (38.0%) were
      polymorphic in both combinations. These results demonstrated that the polymerase
      chain reaction-based InDel markers developed in this study could be of immediate
      use for rice genetic studies and breeding programs.

PMID- 24301784
TI  - Genetic variability of Dactylopius opuntiae (Hemiptera, Dactylopiidae) on forage
      cactus in northeast Brazil.
AB  - The carmine cochineal Dactylopius opuntiae is a key pest in productive fields of
      forage cactus in Pernambuco, Brazil. Species identification by means of molecular
      markers assists in understanding the genetic profile, underpins morphological
      characterization, and supports the monitoring of populations in integrated
      management programs designed to control this pest. We evaluated the genetic
      variability of natural populations of D. opuntiae. Genetic variability was
      analyzed with ISSR and RAPD primers in 24 populations from 12 municipalities of
      Pernambuco State in Brazil. Morphological characterization confirmed that D.
      opuntiae was the only cochineal species present in all samples. Nine ISSR primers
      and six RAPD produced a total of 62 and 58 polymorphic fragments, respectively.
      Both types of markers showed an average genetic similarity of 80% regardless of
      the geographic origin of samples. The low genetic variability demonstrates a high
      degree of relatedness among these D. opuntiae populations. 

PMID- 24301785
TI  - Three-dimensional digital visible heart model and myocardial pathological
      characteristics of fetal single ventricle connected with aortic coarctation.
AB  - This study aimed to provide data for imaging diagnosis and clinical surgical
      plans by reconstructing a three-dimensional (3-D) digital visible heart model of
      single ventricle (SV) connection with aortic coarctation (CoA) and characterizing
      the myocardial and vascular wall pathological characteristics. Fifteen miscarried
      fetus cadavers with SV and CoA were selected. Fourteen cardiac specimens were
      systematically reviewed for segmental anatomy and conventional histological
      examinations. One fetus cadaver was used to obtain the structural dataset of the
      fetal body and to reconstruct a 3-D digital visible heart model. Specimen
      pathological dissection indicated hypertrophic myocardium SV, significant aortic
      wall thickening, and localized coarctation area elevation. Ten cases of SV with
      left ventricular morphology displayed a large muscle ridge and solitus normally
      aligned great arteries. Five cases of SV with right ventricular morphology had
      coarse, parallel trabeculations and received a common atrioventricular valve. The
      reconstructed 3-D heart and the main internal structures were realistic, which
      were beneficial for clinical and image teaching of fetal heart development. The
      change of characteristics of the myocardium and great vascular wall was obvious
      and may be the critical cause leading to progressive dysfunction in the postnatal
      heart. 

PMID- 24301786
TI  - Expression of tyrosine hydroxylase and growth-associated protein 43 in aging
      atrial fibrillation patients of Xinjiang Uygur and Han nationality.
AB  - The aim of this study was to explore the changes in gene and protein expressions
      of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in aging
      atrial fibrillation patients of Xinjiang Uygur and Han nationality, and the
      significance of the changes. Real-time polymerase chain reaction and Western blot
      analysis were used to detect gene and protein expressions of TH and GAP43 in
      atrial tissues of 54 patients with valvular heart disease. mRNA and protein
      expressions of GAP43 and TH were significantly different between the sinus rhythm
      and atrial fibrillation groups (P < 0.05). Protein expressions of GAP43 and TH of
      both nationalities differed significantly between the sinus rhythm group and the
      atrial fibrillation group (P < 0.05), whereas there was no statistical difference
      between the two nationalities within each group (P > 0.05). Protein expressions
      of GAP43 and TH differed significantly among different age groups of different
      nationalities in the sinus rhythm and atrial fibrillation groups (P < 0.05); only
      protein expression of GAP43 differed significantly in different age groups in the
      atrial fibrillation group (P < 0.05). The changes of mRNA and protein expressions
      of TH and GAP43 played a vital role in the process of maintaining the atrial
      fibrillation. Therefore, increased expression of TH and GAP43 might be a
      molecular mechanism for left atrial myoelectricity remodeling of aging atrial
      fibrillation patients, which might be potential therapeutic targets of atrial
      fibrillation. 

PMID- 24301787
TI  - Inhibitory effect of microRNA-24 on fatty acid-binding protein expression on 3T3
      L1 adipocyte differentiation.
AB  - We examined the effect of microRNAs on 3T3-L1 adipocyte differentiation and
      expression of adipocyte-specific gene fatty acid-binding protein 4 (FABP4). We
      screened and identified adipo-related microRNAs during 3T3-L1 adipocyte
      differentiation with a microRNA microarray. High expression plasmids of miR-24
      and miR-21 were constructed and transfected into 3T3-L1 preadipocytes by
      lipofectamine. The effects of miR-24 and miR-21 on 3T3-L1 adipocyte
      differentiation were observed, and the protein and mRNA expression levels of
      FABP4 and AP-1 were determined. The expression profiles of microRNAs
      significantly changed during 3T3-L1 adipocyte differentiation. The expression of
      33 microRNAs was downregulated, among which downregulation of miR-24 was the most
      extensive. There were 17 microRNAs with upregulated expression; the highest
      levels were found for miR-21. miR-24 significantly inhibited 3T3-L1 adipocyte
      differentiation and maturity, while miR-21 had no significant effect. In
      addition, miR-24 significantly inhibited the expression of FABP4, while it
      upregulated AP-1 expression, but had no effect on the level of FABP4 mRNA. miR-21
      had no effect on FABP4 protein and mRNA expression. AP-1 silencing could, at
      least partially, reverse the inhibitory effect of miR-24 on FABP4 expression. We
      conclude that microRNA expression profiles change significantly during 3T3- L1
      adipocyte differentiation and that miR-24 plays an important role in regulating
      adipocyte differentiation and FABP4 expression. The mechanism involved may be the
      upregulation of AP-1. 

PMID- 24301788
TI  - Isolation and characterization of microsatellite markers for Bertholletia excelsa
      (Lecythidaceae) population genetic analysis.
AB  - Seven polymorphic microsatellite markers were developed and validated for
      Bertholletia excelsa (Brazil nut tree) population genetic studies. This species
      is a widespread monotypic Amazonian tree with high non-timber economic value.
      Unfortunately, Brazil nut production is currently less than 25% of historical
      production levels, because of extensive deforestation. All pairs of primers
      produced clearly interpretable and polymorphic bands. No linkage disequilibrium
      was observed in an analysis of 46 individuals from one population, three to seven
      alleles per locus were observed; the expected heterozygosity ranged from 0.378 to
      0.978, with significant heterozygote excess for four loci. An analysis of
      individuals from two populations showed private alleles at all loci. These primer
      pairs will be useful for population studies, especially for comparing samples
      from different parts of the Amazon forest. 

PMID- 24301789
TI  - Impact of forage clipping treatments on performance of winter wheat.
AB  - Farmers in northern parts of Pakistan face severe shortage of green forage for
      their livestock during the harsh winter season. Winter wheat has the potential to
      be used as a dual-purpose crop for forage plus grain production in these areas.
      Ten elite winter wheat lines from Oklahoma State University were evaluated at
      Hazara Research Station Abbottabad under unclipped and clipped treatment level
      during 2005-06. The material was planted in a randomized complete block design
      with three replications, with a row length of four meters and a row to row space
      of 25 cm. Data were recorded on green forage yield, plant height, spike length,
      spikelets/spike, days to maturity, spike weight, biological weight, and grain
      yield. Analysis of variance indicated significant differences among genotypes for
      all traits except spike length. Similarly all traits except spikelets/spike
      exhibited significant differences between unclipped and clipped treatment levels.
      Genotype x clipping interaction was non-significant for all traits except grain
      yield. Overall, winter wheat lines OK98G508W and OK00611W performed better for
      important traits such as early maturity, biological yield and grain yield,
      although over-environment testing is needed before recommendations can be made to
      the farmers. 

PMID- 24301790
TI  - Association of chemotactic factor receptor 5 gene with breast cancer.
AB  - We designed a 2-stage study to investigate chemotactic factor receptor 5 (CCR5)
      gene expression in breast cancer tissues and axillary lymph nodes and analyze the
      association between the CCR5-I"32 gene polymorphism and the clinical features and
      prognosis of breast cancer patients. The first stage examined 72 cases of
      invasive ductal carcinoma and axillary lymph node tissue, 50 cases of breast
      fibroadenoma tissue, and 40 cases of normal breast tissue. The tissues specimens
      were embedded in paraffin, and CCR5 expression was detected using
      immunohistochemical methods. C-erbB-2, p53, Ki-67, estrogen receptor, and
      progesterone receptor expression were also detected in the breast cancer tissues.
      The second stage examined 35 cases of surgically removed tissue. Relative
      expression levels of CCR5 messenger RNA (mRNA) in primary foci, axillary lymph
      node, and cancer-adjacent tissues of the breast cancer and breast fibroadenoma
      samples were detected using real-time quantitative reverse transcription
      polymerase chain reaction assay. We found that 1) CCR5 mRNA relative expression
      levels in breast cancer tissue were significantly higher than those in adjacent
      normal tissue (P < 0.01) and benign tumors (P < 0.05). The relative CCR5 mRNA
      relative expression level between phase II and phase III breast cancer tissues
      was statistically significant (P < 0.05). The CCR5 mRNA relative expression level
      between adjacent normal tissues and fibroadenoma tissues was not significantly
      different (P > 0.05). 2) Relative CCR5 mRNA expression level was significantly
      higher in metastatic lymph node tissues than that in non-metastatic lymph nodes
      (P < 0.05), and 3) CCR5 expression in breast cancer tissue was positively
      correlated with axillary lymph node metastasis (chi-square = 4.982, P = 0.026, r
      = 0.305). CCR5 expression was mildly and positively correlated with the oncogene
      C-erbB-2 (P < 0.05, r = 0.291). 4) CCR5 expression in breast cancer tissue was
      not correlated with age, menopause, maximum tumor size, tumor phase, p53, Ki-67,
      estrogen receptor, progesterone receptor, or other clinical features (P > 0.05).
      We concluded that CCR5 expression significantly increases in breast cancer
      tissues and metastatic lymph nodes. CCR5 plays a role in breast cancer
      development and axillary lymph node metastasis. It can be used indirectly as an
      indicator of axillary lymph node metastasis and prognosis. 

PMID- 24301791
TI  - ADAMTS14 gene polymorphism associated with knee osteoarthritis in Thai women.
AB  - Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. This
      disease is characterized by breakdown and loss of articular cartilage due to
      genetic, mechanical and environmental factors. Although the pathophysiology of OA
      is not completely known, several candidate genes have been reported to be
      associated with OA susceptibility. We assessed the association between genetic
      variation in the ADAMTS14 region and knee osteoarthritis susceptibility in the
      Thai population. The rs4747096 SNP was genotyped by PCR-RFLP on genomic DNA
      extracted from peripheral blood of 108 OA patients and 119 controls. The PCR
      product (196 bp) was digested with BspEI. A sample with the GG genotype showed
      two band sizes of 158 and 38 bp, while a sample with the AA genotype showed a
      single band size of 196 bp. Heterozygotes with the AG genotype showed all three
      corresponding bands. Genotype distributions, allele frequencies and model of
      inheritance in patients and controls were compared. In females, the frequency of
      the AA genotype and the A allele were significantly higher in knee OA patients
      than in controls [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 1.05
      7.59 and OR = 1.58, 95%CI = 1.00-2.45, respectively]. Moreover, genotypic AA and
      AG were associated with significantly increased risk for knee OA when compared to
      GG (OR = 2.72, 95%CI = 1.10-6.87). No significant associations were observed in
      males. In conclusion, the nsSNP rs4747096 in ADAMTS14 was associated with knee OA
      in female Thai patients; therefore, the role of ADAMTS14 in OA seems to be gender
      dependent. 

PMID- 24301792
TI  - Molecular analysis of East Anatolian traditional plum and cherry accessions using
      SSR markers.
AB  - We conducted SSR analyses of 59 accessions, including 29 traditional plum (Prunus
      domestica), 24 sweet cherry (Prunus avium), and 1 sour cherry (Prunus cerasus)
      selected from East Anatolian gene sources and 3 plum and 2 cherry reference
      accessions for molecular characterization and investigation of genetic
      relationships. Eight SSR loci [1 developed from the apricot (UDAp-404), 4 from
      the peach (UDP96-010, UDP96-001, UDP96-019, Pchgms1) and 3 from the cherry (UCD
      CH13, UCD-CH17, UCD-CH31) genome] for plum accessions and 9 SSR loci [5 developed
      from the cherry (PS12A02, UCD-CH13, UCD-CH17, UCD-CH31, UCD-CH21), 3 from the
      peach (Pchgms1, UDP96-001, UDP96-005) and 1 from the plum (CPSCT010) genome] for
      cherry accessions were used for genetic identification. A total of 66 and 65
      alleles were obtained in the genetic analyses of 31 plum and 28 cherry
      accessions, respectively. The number of alleles revealed by SSR analysis ranged
      from 4 to 14 alleles per locus, with a mean value of 8.25 in plum accessions, and
      from 5 to 10 alleles per locus with a mean value of 7.2 in cherry accessions.
      Only one case of synonym was identified among the cherry accessions, while no
      case of synonym was observed among the plum accessions. Genomic SSR markers used
      in discrimination of plum and cherry accessions showed high cross-species
      transferability in the Prunus genus. Because of their appreciable polymorphism
      and cross species transferability, the SSR markers that we evaluated in this
      study will be useful for studies involving fingerprinting of cherry and plum
      cultivars. 

PMID- 24301793
TI  - Cloning and expression analysis of Wnt6 and Hox6 during intestinal regeneration
      in the sea cucumber Apostichopus japonicus.
AB  - Many developmental genes play important roles in regeneration. Here, we cloned
      the two developmental genes, Wnt6 and Hox6, from Apostichopus japonicus by rapid
      amplification of cDNA ends (RACE) polymerase chain reaction (PCR). The Wnt6 full
      length cDNA is 1140 bp long with a 1029-bp open reading frame encoding 342 amino
      acids. The deduced Wnt6 protein contained a 22-amino acid signal peptide and a
      274-amino acid mature peptide. The Hox6 (AjHBOX6) full-length cDNA contained 1312
      bp with a 966-bp open reading frame encoding 321 amino acids. Its deduced amino
      acid sequence included one homeodomain (60 amino acids) and three domains with
      low compositional complexity. Comparison and phylogenetic analysis revealed that
      Wnt6 and Hox6 in A. japonicus had the nearest relationship to those in sea
      urchins. Further expression analysis by real-time PCR showed that Wnt6 and Hox6
      were apparently upregulated during intestine regeneration, which suggested that
      they were involved in the intestinal regeneration of sea cucumbers. 

PMID- 24301794
TI  - Phylogenetic relationships of chrysanthemums in Korea based on novel SSR markers.
AB  - Chrysanthemums are well known for their esthetic and medicinal values.
      Characterization of chrysanthemums is vital for their conservation and management
      as well as for understanding their genetic relationships. We found 12 simple
      sequence repeat markers (SSRs) of 100 designed primers to be polymorphic. These
      novel SSR markers were used to evaluate 95 accessions of chrysanthemums (3
      indigenous and 92 cultivated accessions). Two hundred alleles were identified,
      with an average of 16.7 alleles per locus. KNUCRY-77 gave the highest polymorphic
      information content value (0.879), while KNUCRY-10 gave the lowest (0.218).
      Similar patterns of grouping were observed with a distance-based dendrogram
      developed using PowerMarker and model-based clustering with Structure. Three
      clusters with some admixtures were identified by model-based clustering. These
      newly developed SSR markers will be useful for further studies of chrysanthemums,
      such as taxonomy and marker-assisted selection breeding. 

PMID- 24301795
TI  - Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.
AB  - BACKGROUND: Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no
      established treatment. Gait ataxia is a prominent feature causing substantial
      disability. Understanding the evolution of the gait disturbance is a key step in
      developing treatment strategies. METHODS: We studied 9 gait variables in 24 SCA6
      (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with
      clinical severity (presymptomatic and symptomatic). RESULTS: Discrete gait
      characteristics precede symptoms in SCA6 with significantly increased variability
      of step width and step time, whereas a more global gait deficit was evident in
      symptomatic individuals. Gait characteristics discriminated between
      presymptomatic and symptomatic individuals and were selectively associated with
      disease severity. CONCLUSIONS: This is the largest study to include a detailed
      characterization of gait in SCA6, including presymptomatic subjects, allowing
      changes across the disease spectrum to be compared. Selective gait disturbance is
      already present in SCA6 before clinical symptoms appear and gait characteristics
      are also sensitive to disease progression. Early gait disturbance likely reflects
      primary pathology distinct from secondary changes. These findings open the
      opportunity for early evaluation and sensitive measures of therapeutic efficacy
      using instrumented gait analysis which may have broader relevance for all
      degenerative ataxias.

PMID- 24301797
TI  - CCK8 negatively regulates the TLR9-induced activation of human peripheral blood
      pDCs by targeting TRAF6 signaling.
AB  - Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive
      secretion of type I interferon in response to foreign nuclei acids. Combined with
      their antigen presentation capacity, this powerful functionality enables pDCs to
      orchestrate innate and adaptive immune responses. Cholecystokinin octapeptide
      (CCK8) is a potent immunomodulator, whose role in pDCs function is unknown. In
      this study, we found that two different cholecystokinin receptors, CCK1R and
      CCK2R, are expressed on human peripheral blood pDCs. Exogenous CCK8 was able to
      modulate the TLR-induced activation of pDCs, including phenotypic maturation, IFN
      alpha synthesis and secretion, and could also regulate the potential of pDCs to
      induce adaptive immune responses in vitro. CCK8 inhibited TLR9-induced activation
      of tumor-necrosis factor receptor-associated factor 6, which is an important
      adapter protein in activation of interferon-regulatory factor (IRF)5 and IRF7,
      possibly through CCK2R, by evoking the activity of protein kinase (PK)A and
      reducing the activity of PKC. All these results indicate that CCK8 can inhibit
      the TLR9-induced phenotypic maturation and activation of pDCs, acting through
      CCK2R by modulating the tumor-necrosis factor receptor-associated factor 6
      signaling pathways. 

PMID- 24301798
TI  - Toward rapid preparation of capillary columns for electrochromatography use.
AB  - CEC is a high performance electrodriving liquid phase separation technique. It
      does not need complex and sophisticated high pressure instrumentation for
      nanoflow driving. This is attractive for parallel multicolumn analysis. To this
      end, high throughput methods for column preparation are needed to support the use
      of multiple columns. In this study, we directly used CEC mobile phase solution as
      the packing solvent, and realized rapid preparation of capillary columns based on
      a single particle fritting technology. The method presented high preparation
      throughput compared with other reported methods based on various fritting
      technologies. The single particle fritting approach promoted column preparation
      throughput to 1 column/h, including all the fritting, packing and conditioning
      steps. The rapidly prepared columns showed consistently high efficiency of up to
      150 000 plates per meter, and usefulness in reversed phase CEC of neutral,
      charged and biomolecules. With standard peptides as the sample, excellent long
      term reproducibility (better than 0.8%RSD, ten days, for retention times) was
      observed. 

PMID- 24301799
TI  - A dual enzyme functionalized nanostructured thulium oxide based interface for
      biomedical application.
AB  - In this paper, we present results of the studies related to fabrication of a rare
      earth metal oxide based efficient biosensor using an interface based on
      hydrothermally prepared nanostructured thulium oxide (n-Tm2O3). A colloidal
      solution of prepared nanorods has been electrophoretically deposited (EPD) onto
      an indium-tin-oxide (ITO) glass substrate. The n-Tm2O3 nanorods are found to
      provide improved sensing characteristics to the electrode interface in terms of
      electroactive surface area, diffusion coefficient, charge transfer rate constant
      and electron transfer kinetics. The structural and morphological studies of n
      Tm2O3 nanorods have been carried out by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR)
      spectroscopic techniques. This interfacial platform has been used for fabrication
      of a total cholesterol biosensor by immobilizing cholesterol esterase (ChEt) and
      cholesterol oxidase (ChOx) onto a Tm2O3 nanostructured surface. The results of
      response studies of the fabricated ChEt-ChOx/n-Tm2O3/ITO bioelectrode show a
      broad linear range of 8-400 mg dL(-1), detection limit of 19.78 mg (dL cm(-2))(
      1), and high sensitivity of 0.9245 MUA (mg per dL cm(-2))(-1) with a response
      time of 40 s. Further, this bioelectrode has been utilized for estimation of
      total cholesterol with negligible interference (3%) from analytes present in
      human serum samples. The utilization of this n-Tm2O3 modified electrode for
      enzyme-based biosensor analysis offers an efficient strategy and a novel
      interface for application of the rare earth metal oxide materials in the field of
      electrochemical sensors and bioelectronic devices. 

PMID- 24301802
TI  - Chemistry of male mandibular gland secretions ofPhilanthus basilaris cresson
      andPhilanthus bicinctus (Mickel) (Hymenoptera: Sphecidae).
AB  - Detailed chemical characterizations are provided for the species-specific
      mixtures of marking pheromones utilized by the male beewolvesPhilanthus basilaris
      andP. bicinctus. Successful analysis of these complex mixtures of 2-ketones,
      fatty acids, ethyl esters, and aldehydes was facilitated by the treatment of the
      crude extracts with 1,1-dimethylhydrazine and direct analysis of the resulting
      hydrazones, methyl esters, and starting ethyl esters by GC-MS. 

PMID- 24301803
TI  - Preliminary isolation of male-inhibitory pheromone of the spiderSchizocosa
      ocreata (Araneae, Lycosidae).
AB  - Compounds with pheromone activity were extracted from maleSchizocosa ocreata silk
      using methanol as the solvent. Behavioral data suggest that these compounds
      mediate agonistic encounters among male spiders. Preliminary chemical analyses
      indicate that the pheromones are low-molecular-weight lipids, one being slightly
      polar, the other nonpolar. 

PMID- 24301801
TI  - Glutamine-driven oxidative phosphorylation is a major ATP source in transformed
      mammalian cells in both normoxia and hypoxia.
AB  - Mammalian cells can generate ATP via glycolysis or mitochondrial respiration.
      Oncogene activation and hypoxia promote glycolysis and lactate secretion. The
      significance of these metabolic changes to ATP production remains however ill
      defined. Here, we integrate LC-MS-based isotope tracer studies with oxygen uptake
      measurements in a quantitative redox-balanced metabolic flux model of mammalian
      cellular metabolism. We then apply this approach to assess the impact of Ras and
      Akt activation and hypoxia on energy metabolism. Both oncogene activation and
      hypoxia induce roughly a twofold increase in glycolytic flux. Ras activation and
      hypoxia also strongly decrease glucose oxidation. Oxidative phosphorylation,
      powered substantially by glutamine-driven TCA turning, however, persists and
      accounts for the majority of ATP production. Consistent with this, in all cases,
      pharmacological inhibition of oxidative phosphorylation markedly reduces energy
      charge, and glutamine but not glucose removal markedly lowers oxygen uptake.
      Thus, glutamine-driven oxidative phosphorylation is a major means of ATP
      production even in hypoxic cancer cells. 

PMID- 24301796
TI  - Dietary factors modulate Helicobacter-associated gastric cancer in rodent models.
AB  - Since its discovery in 1982, the global importance of Helicobacter pylori-induced
      disease, particularly in developing countries, remains high. The use of rodent
      models, particularly mice, and the unanticipated usefulness of the gerbil to
      study H. pylori pathogenesis have been used extensively to study the interactions
      of the host, the pathogen, and the environmental conditions influencing the
      outcome of persistent H. pylori infection. Dietary factors in humans are
      increasingly recognized as being important factors in modulating progression and
      severity of H. pylori-induced gastric cancer. Studies using rodent models to
      verify and help explain mechanisms whereby various dietary ingredients impact
      disease outcome should continue to be extremely productive. 

PMID- 24301800
TI  - Timescales and bottlenecks in miRNA-dependent gene regulation.
AB  - MiRNAs are post-transcriptional regulators that contribute to the establishment
      and maintenance of gene expression patterns. Although their biogenesis and decay
      appear to be under complex control, the implications of miRNA expression dynamics
      for the processes that they regulate are not well understood. We derived a
      mathematical model of miRNA-mediated gene regulation, inferred its parameters
      from experimental data sets, and found that the model describes well time
      dependent changes in mRNA, protein and ribosome density levels measured upon
      miRNA transfection and induction. The inferred parameters indicate that the
      timescale of miRNA-dependent regulation is slower than initially thought. Delays
      in miRNA loading into Argonaute proteins and the slow decay of proteins relative
      to mRNAs can explain the typically small changes in protein levels observed upon
      miRNA transfection. For miRNAs to regulate protein expression on the timescale of
      a day, as miRNAs involved in cell-cycle regulation do, accelerated miRNA turnover
      is necessary. 

PMID- 24301804
TI  - Attractancy and species specificity of 6-acetoxy-5-hexadecanolide, a mosquito
      oviposition attractant pheromone.
AB  - Four stereoisomers of 6-acetoxy-5-hexadecanolide, a mosquito oviposition
      attractant pheromone, were bioassayed for their activity on mosquitoes. Only (-)
      (5R,6S) isomer was active in attractingCulex quinquefasciatus Say females for
      oviposition at dosages of 0.5 MUg/100 ml water and above with the floating-cap
      method. The activity of this isomer increased 50-fold when it was applied
      directly to the water surface. The other three isomers, (+)-(5S,6R), (+)-(5R,6R),
      and (-)-(5s, 6s), were not active. The active isomer was ovipositionally
      attractive not only toC. quinquefasciatus but also toC. tarsalis Coquillett;
      however, it was 100 times more active in the former than in the latter
      species.Aedes aegypti (L.) andAnopheles quadrimaculatus Say were not attracted to
      the pheromone, thus suggesting that the pheromone is genus-specific. 

PMID- 24301805
TI  - Chemistry and functions of exocrine secretions of the antsTapinoma melanocephalum
      and T. erraticum.
AB  - Volatile constituents produced by ant workers belonging to the speciesTapinoma
      melanocephalum andT. erraticum have been analyzed by gas chromatography-mass
      spectrometry. The pygidial (=anal) gland secretion ofT. melanocephalum is
      fortified with 6-methyl-5-hepten-2-one and actinidine (the mass spectrum of which
      is corrected in this paper). An unidentified compound was detected in cephalic
      extracts. The pygidial gland secretion ofT. erraticum was also dominated by 6
      methyl-5-hepten-2-one, in addition to two isomers of iridodial, and
      iridomyrmecin. The sternal glands contained iridodial and C15-C20 hydrocarbons.
      Workers ofT. melanocephalum effectively utilize their pygidial gland secretions
      as an alarm-defense system during aggressive encounters with workers ofSolenopsis
      geminata. 6-Methyl-5-hepten-2-one is active as a releaser of alarm behavior, and
      actinidine is repellent to workers ofT. melanocephalum. Cephalic extracts
      possessed attractant and arrestant properties for workers of this species. 

PMID- 24301806
TI  - New natural aliphatic ethers in cuticular waxes of gregarious and solitary
      locustsLocusta migratoria cinerascens (II).
AB  - An original homologous series of di-n-alkyl ethers has been revealed in the
      cuticular waxes ofLocusta migratoria cinerascens. The mass spectrometry-electron
      impact, and positive and negative chemical ionization of these derivatives has
      been investigated in order to define the optimal conditions for structural
      determination. The quantitative analyses have shown that the ethers C n1H2n1 + 1
      O-C n2H2n2+1 with an odd number of carbon atoms (n1 even andn2 odd) are clearly
      predominant. Furthermore, they have made a double phasal dimorphism appear:
      heavier ethers in the case of the solitary insects and majority participation ofn
      alkyl chains in C16 (60%) in the case of the gregarious locusts and in C18 (50%)
      in the solitary ones. 

PMID- 24301807
TI  - Effects of diet breadth on autogenous chemical defense of a generalist
      grasshopper.
AB  - The lubber grasshopper,Romalea guttata, produces a metathoracic defensive
      secretion containing primarily phenolics and quinones. This insect feeds on a
      wide range of plant species. Insects reared on an artificial diet and a diet of
      onion,Allium canadense, had secretions that contained fewer compounds, lower
      concentrations of compounds, and markedly altered relative composition of
      components compared to insects reared on a varied diet of 26 plant species that
      included onion. The study demonstrates that diet breadth has a major effect on
      the quality and quantity of the autogenous defensive secretion of this generalist
      herbivore. The results are compared to diet effects known in chemically defended
      specialists. Two possible mechanisms explaining the effects of diet breadth are
      proposed: one involves changes in precursor availability with changing diet
      breadth; the other suggests that physiological stress due to diet restriction
      changes allocation of resources to chemical defense. 

PMID- 24301808
TI  - Allelopathic effects ofChrysanthemum morifolium on germination and growth of
      several herbaceous plants.
AB  - Aqueous extracts obtained from young green tops ofChrysanthemum morifolium
      inhibited the germination of six flowering plants, including chrysanthemum
      itself, provided for experiments. The same phenomenon was also clearly observed
      when powder made from young green tops and old leaves of chrysanthemum was used.
      Moreover, the growth of seedlings planted again in garden soil which was once
      used for the culture of chrysanthemum was greatly interrupted. Chrysanthemum
      cultured in used garden soil showed far less dry weight than that cultured in
      fresh garden soil. The weight of chrysanthemum cultured using its root exudates
      was also less than that cultured with water leachate of fresh garden soil, and
      therefore these results may be considered to indicate allelopathic effects. In
      order to find the allelochemicals related to this phenomenon, benzoic acid and
      phenolic acids such as salicylic,p-hydroxybenzoic, vanillic, gentisic,
      protocatechuic, syringic, gallic, ferulic, and caffeic acids were identified by
      gas chromatography. 

PMID- 24301809
TI  - Plant secondary compounds as oviposition deterrents for cabbage butterfly,Pieris
      rapae (Lepidoptera: Pieridae).
AB  - Oviposition byPieris rapae butterflies was deterred by spraying the plant
      secondary compounds coumarin and rutin on cabbage plants in greenhouse choice
      tests. In no-choice tests ranging from 5 min to 24 hr, acceptance of rutin
      treated plants for oviposition increased with trial duration. Both coumarin and
      rutin deterred oviposition primarily by affecting prealighting rather than
      postalighting behavior, indicating that deterrence was mediated by noncontact
      cues. 

PMID- 24301810
TI  - Separation and identification of phenolic acids and related compounds by gas
      chromatography and fourier transform infrared spectroscopy.
AB  - Phenolic acids and related compounds were separated by gas chromatography using
      three separate columns. One of these columns was coupled to a Fourier transform
      infrared spectrometer. The trimethylsilyl derivatives could be separated and
      identified by comparing the relative retention times of the three different
      columns. However, where there was overlap, the accompanying infrared data clearly
      distinguished between the questionable derivatives, thus enabling
      characterization of all derivatives. 

PMID- 24301811
TI  - Synthesis of racemate and enantiomers of 15-methyltritriacontane, sex-stimulant
      pheromone of stable flyStomoxys calcitrans L.
AB  - The synthesis of the racemate and two enantiomers of 15-methyltritriacontane (1),
      an active component of the sex-stimulant pheromone ofStomoxys calcitrans L., is
      described. Racemic 15-methyltritriacontane was synthesized in four steps from 1
      hexadecene with a 72% overall yield. Both theR- andS-enantiomers were synthesized
      in eight steps, respectively, starting from optically pure (R)-(+)-pulegone. 

PMID- 24301812
TI  - Responses of parasiteEdovum puttleri to kairomone from eggs of colorado potato
      beetle,Leptinotarsa decemlineata.
AB  - When females of the eulophid parasiteEdovum puttleri were exposed to ann-hexane
      wash of eggs of the Colorado potato beetle,Leptinotarsa decemlineata, their
      responses indicated that the eggs contained a kairomone which elicited host
      finding and host-acceptance behaviors. The hostfinding responses included an
      increased amount of time searching glass beads treated with kairomone, and
      drumming on the beads with the flagellum of the antennae. Host-acceptance
      responses included grasping of the beads with the legs, raising of the abdomen,
      and probing the kairomone-treated surface with the ovipositor. None of these
      responses were noted in females on beads treated only with hexane, or in males
      exposed to kairomone-treated beads. When kairomone was applied to a flat surface,
      filter paper disks, few episodes of drumming and no episodes of probing with the
      ovipositor were noted. Responses ofE.puttleri to eggs of Colorado potato beetle
      were similar to those on kairomone-treated beads, but females normally drilled
      into eggs and fed on host fluids after retracting the ovipositor. The kairomone
      is volatile, and responsiveness was reduced in parasites exposed to beads treated
      several hours previously. 

PMID- 24301813
TI  - Copulation releaser pheromone in body scales of female whitemarked tussock
      moth,Orgyia leucostigma (Lepidoptera: Lymantriidae): Identification and
      behavioral role.
AB  - The copulatory behavior of the male whitemarked tussock moth,Orgyia leucostigma,
      was released by extracts of female body scales applied to rubber septum models
      baited with a female sex pheromone gland. The major compounds in the scale
      extracts were identified by GC-MS as a series ofn-alkanes from C-21 to C-29. Of
      these,n-tricosane,n-tetracosane,n-pentacosane, andn-heptacosane, applied at 10
      ng/septum, caused significantly more males to attempt copulation than hexane
      treated controls. Mixtures of then-alkanes, resembling the composition in the
      scale extracts, were no better than the two most active alkanes,n-tetracosane
      andn-pentacosane, alone. The releaser effect of then-alkanes was dose dependent.
      EAG responses to the identifiedn-alkanes were small suggesting, along with the
      behavioral observations, that their perception occurred at very close range.
      Other factors releasing male copulatory behavior are discussed. 

PMID- 24301814
TI  - Synthesis of enantiomerically enriched 2-heptanol and 3-octanol by microbial
      reductases ofCurvularia falcata andMucor species.
AB  - Certain insects produce 2-heptanol or 3-octanol in various glandular secretions
      and recent studies have shown that the 3-octanol of two different genera of ants
      (Crematogaster andMyrmica) can be either the (S)-(+) or mainly the (R)-(-)
      enantiomer, respectively. Synthesis of each of these alcohols can be achieved in
      relatively high enantiomeric purity by certain microbial reductases. The
      corresponding ketone of each alcohol is reduced byCurvularia falcata, giving an
      alcohol which is about 90% the (S)-(+) enantiomer, and twoMucor species give as
      much as 80% the (R)-(-) enantiomer. The synthesis of certain chiral alcohols from
      their corresponding ketones by microbial reductases can offer a simple procedure
      for obtaining sufficient amounts of these substances for certain behavioral
      studies. 

PMID- 24301815
TI  - Importance of lichen secondary products in food choice of two oribatid mites
      (Acari) in an alpine meadow ecosystem.
AB  - In an alpine meadow ecosystem in the Swiss National Park, the lichensCetraria
      islandica andCladonia symphycarpa occur in small vegetation patches dominated
      byCarexfirma (Cyperaceae) andSesleria coerulea (Gramineae). Laboratory food
      choice experiments with two oribatid mitesFuscozetes setosus andCarabodes
      intermedius show that the thallus structure and secondary products ofC. islandica
      are repellent factors against herbivorous mites. In contrast, secondary products
      ofC. symphycarpa may be an attractant for the mites. 

PMID- 24301816
TI  - Intranidal worker reactions to volatile compounds identified from cephalic
      secretions in the stingless bee,Scaptotrigona postica (Hymenoptera, Meliponinae).
AB  - From pentane extracts of worker heads of the stingless bee (Scaptotrigona
      postica), 70 volatile compounds were identified by combined gas chromatographic
      mass spectroscopic analyses. A bioassay was developed to evaluate intranidal
      reactions of workers to synthetic volatiles. Thirty-six of the cephalic volatiles
      were tested. Thirteen types of behavioral reactions were recorded in a
      semiquantitative manner. The test was run in the brood nest where mainly young
      nurse bees are present and also in the storage area of the nest with old foragers
      traffic. The results obtained were compared and discussed in order to understand
      the chemical communication system of this species. Especially in the dark
      interior of the nest, which in nature is found in hollow tree cavities, chemical
      messages obviously play a particularly important role in the communication
      systems of the bees. 

PMID- 24301817
TI  - Sex pheromones of the sea lamprey (Petromyzon marinus): Steroid studies.
AB  - Pheromone-containing and pheromone-devoid samples of male sea lamprey (Petromyzon
      marinus) urine were analyzed for the concentrations of nine steroids
      [dehydroepiandrosterone (DHEA), testosterone (T), dihydrotestosterone (DHT),
      progesterone (P), androstenedione (A), estrone (E1), estradiol (E2),
      corticosterone (B), and cortisol (F)] by radioimmunoassay (RIA). Samples analyzed
      included native urine that had been enzymatically hydrolyzed with mixed beta
      glucuronidase/sulfatase. Values of the analyses were used to prepare solutions of
      the individual steroids for bioassay at concentrations which bracketed the
      urinary concentrations. Results show that only testosterone elicited a preference
      response in spawning-run female sea lampreys, and in concentrations three to four
      orders of magnitude greater than those found in active, unhydrolyzed male urine.
      The possibility that testosterone acts as a pheromone in this species is
      discussed. 

PMID- 24301818
TI  - The promotion of antimicrobial activity on silicon substrates using a "click"
      immobilized short peptide.
AB  - We demonstrated, for the first time, that the short antimicrobial peptide Tet213
      could be conjugated onto the silicon surface by Cu(I)-catalyzed azide-alkyne
      cycloaddition (CuAAC). The modified surface exhibited excellent antimicrobial
      activity against S. aureus and E. coli, and low cytotoxicity to rat bone
      mesenchymal stem cells (rBMSCs).

PMID- 24301819
TI  - D1 polypeptide degradation may regulate psbA gene expression at transcriptional
      and translational levels in Synechocystis sp. PCC 6803.
AB  - Light has been suggested to regulate both synthesis and degradation of the
      Photosystem II (PS II) reaction centre polypeptide D1, encoded by the psbA gene.
      The modified degradation rate of the D1 polypeptide in site-directed
      Synechocystis sp PCC 6803 D1 mutants CA1 [del(E242-E244);Q241H], E243K and E229D
      has provided a tool to determine whether the rate of D1 polypeptide synthesis is
      directly regulated by light-intensity-related factors or by a control mechanism
      mediated by light-dependent degradation of the D1 polypeptide. In vivo
      accumulation of [(35)S] methionine into the D1 polypeptide was found to correlate
      with D1 polypeptide degradation rather than with incident irradiance. This
      suggests that the degradation rate of the D1 polypeptide regulates its own
      synthesis at translational level. Furthermore, several fold differences in the
      psbA mRNA levels were measured between D1 mutant strains, indicating that the
      psbA gene transcription is not solely under light control. 

PMID- 24301820
TI  - Photoinhibition of Photosystem I electron transfer activity in isolated
      Photosystem I preparations with different chlorophyll contents.
AB  - Photoinhibition of the light-induced Photosystem I (PS I) electron transfer
      activity from the reduced dichlorophenol indophenol to methyl viologen was
      studied. PS I preparations with Chl/P700 ratios of about 180 (PS I-180), 100 (PS
      I-100) and 40 (PS I(HA)-40) were isolated from spinach thylakoid membranes by the
      treatments with Triton X-100, followed by sucrose density gradient centrifugation
      and hydroxylapatite column chromatography. White light irradiation (1.1 *
      10(4)MUE m(-2) s(-1)) of PS I-180 for 2 hours bleached 50% of the chlorophyll and
      caused a 58% decrease in the electron transfer activity with virtually no loss of
      the primary donor, P700. The flash-induced absorbance change showed the decay
      phase with a half time of about 10 MUs that was attributed to the P700 triplet,
      suggesting that the photoinhibitory light treatment caused the destruction of the
      PS I acceptor(s), Fx and possibly A1. PS I-100 was similarly photobleached by the
      irradiation and the electron transfer activity decreased. There was, however, no
      apparent photoinhibition of the electron transport activity in PS I(HA)-40.
      Photoinhibition similar to that seen in PS I-180 also occurred in membrane
      fragments that were isolated without any detergent from a PS II-deficient mutant
      strain of the cyanobacterium Synechocystis sp. PCC 6803. PS I-180 was not
      photoinhibited under anaerobic conditions. The production of superoxide and fatty
      acid hydroperoxide during white light irradiation was significantly greater in PS
      I-180 than in PS I(HA)-40. The mechanism of photoinhibition in PS I preparations
      is discussed in relation to the formation of toxic oxygen molecules. 

PMID- 24301821
TI  - Two forms of the Photosystem II D1 protein alter energy dissipation and state
      transitions in the cyanobacterium Synechococcus sp. PCC 7942.
AB  - Synechococcus sp. PCC 7942 (Anacystis nidulans R2) contains two forms of the
      Photosystem II reaction centre protein D1, which differ in 25 of 360 amino acids.
      D1: 1 predominates under low light but is transiently replaced by D1:2 upon
      shifts to higher light. Mutant cells containing only D1:1 have lower
      photochemical energy capture efficiency and decreased resistance to
      photoinhibition, compared to cells containing D1:2. We show that when dark
      adapted or under low to moderate light, cells with D1:1 have higher non
      photochemical quenching of PS II fluorescence (higher qN) than do cells with
      D1:2. This is reflected in the 77 K chlorophyll emission spectra, with lower
      Photosystem II fluorescence at 697-698 nm in cells containing D1:1 than in cells
      with D1:2. This difference in quenching of Photosystem II fluorescence occurs
      upon excitation of both chlorophyll at 435 nm and phycobilisomes at 570 nm.
      Measurement of time-resolved room temperature fluorescence shows that Photosystem
      II fluorescence related to charge stabilization is quenched more rapidly in cells
      containing D1:1 than in those with D1:2. Cells containing D1:1 appear generally
      shifted towards State II, with PS II down-regulated, while cells with D1:2 tend
      towards State I. In these cyanobacteria electron transport away from PS II
      remains non-saturated even under photoinhibitory levels of light. Therefore, the
      higher activity of D1:2 Photosystem II centres may allow more rapid photochemical
      dissipation of excess energy into the electron transport chain. D1:1 confers
      capacity for extreme State II which may be of benefit under low and variable
      light. 

PMID- 24301822
TI  - Phosphatase activities in spinach thylakoid membranes-effectors, regulation and
      location.
AB  - The dephosphorylation of seven phosphoproteins associated with Photosystem II or
      its chlorophyll a/b antenna in spinach thylakoids, was characterised. The rates
      were found to fall into two distinct groups. One, rapidly dephosphorylated,
      consisted of the two subunits (25 and 27 kD) of the major light harvesting
      complex of Photosystem II (LHC II) and a 12 kD polypeptide of unknown identity. A
      marked correlation between the dephosphorylation of these three phosphoproteins,
      strongly suggested that they were all dephosphorylated by the same enzyme. Within
      this group, the 25 kD subunit was consistently dephosphorylated most rapidly,
      probably reflecting its exclusive location in the peripheral pool of LHC II. The
      other group, only slowly dephosphorylated, included several PS II proteins such
      as the D1 and D2 reaction centre proteins, the chlorophyll-a binding protein CP43
      and the 9 kD PS II-H phosphoprotein. No dephosphorylation was observed in either
      of the two groups in the absence of Mg(2+)-ions. Dephosphorylation of the two LHC
      II subunits took place in both grana and stroma-exposed regions of the thylakoid
      membrane. However, deposphorylation in the latter region was significantly more
      rapid, indicating a preferential dephosphorylation of the peripheral (or
      'mobile') LHC II. Dephosphorylation of LHC II was found to be markedly affected
      by the redox state of thiol-groups, which may suggest a possible regulation of
      LHC II dephosphorylation involving the ferredoxin-thioredoxin system. 

PMID- 24301823
TI  - Bacteriochlorophyll organization and energy transfer kinetics in chlorosomes from
      Chloroflexus aurantiacus depend on the light regime during growth.
AB  - We have used measurements of fluorescence and circular dichroism (CD) to compare
      chlorosome-membrane preparations derived from the green filamentous bacterium
      Chloroflexus aurantiacus grown in continuous culture at two different light
      intensities. The cells grown under low light (6 MUmol m(-2) s(-1)) had a higher
      ratio of bacteriochlorophyll (BChl) c to BChl a than cells grown at a tenfold
      higher light intensity; the high-light-grown cells had much more carotenoid per
      bacteriochlorophyll.The anisotropy of the QY band of BChl c was calculated from
      steady-state fluorescence excitation and emission spectra with polarized light.
      The results showed that the BChl c in the chlorosomes derived from cells grown
      under high light has a higher structural order than BChl c in chlorosomes from
      low-light-grown cells. In the central part of the BChl c fluorescence emission
      band, the average angles between the transition dipole moments for BChl c
      molecules and the symmetry axis of the chlorosome rod element were estimated as
      25 degrees  and 17 degrees  in chlorosomes obtained from the low- and high-light
      grown cells, respectively.This difference in BChl organization was confirmed by
      the decay associated spectra of the two samples obtained using picosecond single
      photon-counting experiments and global analysis of the fluorescence decays. The
      shortest decay component obtained, which probably represents energy-transfer from
      the chlorosome bacteriochlorophylls to the BChl a in the baseplate, was 15 ps in
      the chlorosomes from high-light-grown cell but only 7 ps in the preparation from
      low-light grown cells. The CD spectra of the two preparations were very
      different: chlorosomes from low-light-grown cells had a type II spectrum, while
      those from high-light-grown cells was of type I (Griebenow et al. (1991) Biochim
      Biophys Acta 1058: 194-202). The different shapes of the CD spectra confirm the
      existence of a qualitatively different organization of the BChl c in the two
      types of chlorosome. 

PMID- 24301824
TI  - Slow exciton trapping in Photosystem II: A possible physiological role.
AB  - Photosystem II, which has a primary photochemical charge separation time of about
      300 ps, is the slowest trapping of all photosystems. On the basis of an analysis
      of data from the literature this is shown to be due to a number of partly
      independent factors: a shallow energy funnel in the antenna, an energetically
      shallow trap, exciton dynamics which are partly 'trap limited' and a large
      antenna. It is argued that the first three of these properties of Photosystem II
      can be understood in terms of protective mechanisms against photoinhibition.
      These protective mechanisms, based on the generation of non photochemical
      quenching states mostly in the peripheral antenna, are able to decrease
      pheophytin reduction under conditions in which the primary quinone, QA, is
      already reduced, due to the slow trapping properties. The shallow antenna funnel
      is important in allowing quenching state-protective mechanisms in the peripheral
      antenna. 

PMID- 24301825
TI  - Antenna organization in purple bacteria investigated by means of fluorescence
      induction curves.
AB  - Fluorescence induction curves of purple bacteria (Rs. rubrum, Rps. viridis and
      Rb. capsulatus) were measured in the sub-millisecond time range employing a xenon
      flash technique. The induction curves of all three species displayed a sigmoidal
      shape. Analysis of the curves showed that none of the species examined had an
      antenna organization of a lake (i.e. unrestricted energy transfer between
      photosynthetic units). The apparent time constants of inter-unit exciton transfer
      were estimated to be approximately 24 ps in the case of LHC 1-containing species
      (Rs. rubrum and Rps. viridis) and 40 ps in the case of the LHC 2-containing
      species Rb. capsulatus. This result demonstrates that LHC 2 (B800-850) acts as a
      sort of insulator between photosynthetic units. Assuming a coordination number of
      6 in the LHC 1-containing species the mean single step energy transfer time
      between adjacent LHC 1 can be estimated to be 4-5 ps. This is not perfectly
      compatible with the much faster Forster transfer rate of <1ps that follows from
      the minimal chromophore-chromophore distances estimated from digital image
      processing of micrographs from stained membranes. It thus may be concluded that
      the photosynthetic units (reaction center plus LHC 1) are loosely arranged in the
      photosynthetic membrane, like in the fluid-mosaic-membrane model, rather than in
      a hexagonally crystalline configuration. 

PMID- 24301826
TI  - Characterisation of a H2O 2-oxidisable cytochrome b-559 in intact chloroplasts
      with a new type of LED Array Spectrophotometer.
AB  - Cytochrome (cyt) b-559 absorbance changes in intact chloroplasts were
      deconvoluted using a previously described LED-Array-Spectrophotometer (Klughammer
      et al. (1990), Photosynth Res 25: 317-327). When intact chloroplasts were
      isolated in the presence of ascorbate, approx. 15% of the total cyt b-559 could
      be transiently oxidised by 200 MUM H2O2 in the dark. This fraction displays low
      potential properties, as it can be also oxidised by menadione in the presence of
      5 mM ascorbate. Heat pretreatment increased the size of this fraction by a factor
      of 3-4. Low concentrations of cyanide (in the MUM range) prolonged the oxidation
      time while high concentrations suppressed the oxidation (I50=1.5 mM KCN). The
      former KCN-effect relates to inhibition of ascorbate dependent H2O2-reduction
      which is catalysed by ascorbate peroxidase, whereas the latter effect reflects
      competition between H2O2 and CN(-) for the same binding site at the cytochrome
      heme. In the light, much lower concentrations of H2O2 were required to obtain
      oxidation, the amplitude depending on light intensity and on the concentration of
      the added H2O2, but never exceeding approx. 15% of the total cyt b-559. In the
      light, but not in the dark, H2O2 also induced the transient oxidation of a cyt f
      fraction similar in size to the H2O2-oxidisable cyt b-559 fraction. In this case,
      H2O2 serves as an acceptor of Photosystem I in conjunction with the ascorbate
      peroxidase detoxification system. Light can also induce oxidation of a 15% cyt b
      559 fraction without H2O2-addition, if nitrite is present as electron acceptor
      and the chloroplasts are depleted of ascorbate. It is concluded that light
      induced cyt b-559 oxidation in vivo is likely to be restricted to the H2O2
      oxidisable cyt b-559 LP fraction and is normally counteracted by ascorbate. 

PMID- 24301828
TI  - College dropouts: The developmental logic of psychosocial moratoria.
AB  - Students who temporarily drop out of college frequently return with a better
      sense of direction. The reasons for this change are poorly understood. This paper
      describes several issues leave takers confront-including self-sustenance,
      autonomy, and escaping a fearful destiny-from a psychodynamic, social, and
      developmental perspective. The implications for psychosocial theories of adult
      development are also discussed. 

PMID- 24301829
TI  - "Underachievement" among markedly accelerated college students.
AB  - This study investigated those few lackluster achievers as could be identified,
      using loose criteria, in a college-level program of academic acceleration. They
      evidenced, on college transcripts, significant differences from high-achieving
      students of comparable ability. Underachieving males appeared less
      psychologically mature and appeared to suffer more internal conflict than
      achieving males, but underachieving females evidenced greater maturity than their
      counterparts. 

PMID- 24301830
TI  - The social context of adolescent self-esteem.
AB  - The global self-esteem of adolescents was examined in relation to two aspects of
      their daily lives: (a) the perceived quality of their relationships with parents
      and peers; and (b) their self-evaluation in the areas of school, popularity, and
      athletics. The quality of relationships with parents made significant
      contributions to the explained variance in self-esteem of both boys and girls.
      The quality of peer relationships made a significant additional contribution for
      girls but not boys. The importance of parent and peer relationships to self
      esteem did not vary as a function of age for either sex. Self-evaluation of
      popularity was related to girls' global self-esteem, while evaluation of school
      performance was more important for boys. 

PMID- 24301831
TI  - The relative importance of parents and friends in adolescent decision making.
AB  - In this study 175 older adolescents (83 males, 92 females) nominated their
      parents, particularly their mothers, then friends of the same sex, as people most
      important in their lives. While parents were rated as more important than friends
      overall, problems were more frequently discussed with close friends. Using a
      matched sampling design, the adolescents' own mothers, fathers, and a close
      friend of the same sex also responded to a scale where parents' or friends'
      opinions might be sought as part of adolescent decision making. As predicted,
      parents were perceived as most important in certain "future-oriented" areas,
      whereas for "current" decisions, friends' opinions were more valued. Several
      areas of possible parent-peer conflict were also identified. 

PMID- 24301832
TI  - Exceptional giftedness in early adolescence and intrafamilial divergent thinking.
AB  - Two groups of boys and their parents (N=54) were given five divergent thinking
      tests as one part of a longitudinal investigation on exceptional giftedness in
      early adolescence. One groups of adolescents was selected because their IQs were
      above 150, and the other group, was selected because of their outstanding math
      science abilities. Canonical and bivariate analyses indicated that there was a
      strong correlation between the adolescents' divergent thinking test scores and
      their parents' divergent thinking test scores (Rc=.55). Additionally, there was
      some indication that these correlations differed in the two exceptionally gifted
      groups, with the high-IQ group having divergent thinking test scores related to
      those of both parents, and the math-science group having divergent thinking test
      scores related only to those of their mothers. These findings are very consistent
      with earlier investigations on exceptionally gifted adolescents. 

PMID- 24301833
TI  - On the measurement of friend behavior in research on friend influence and
      selection: Findings from longitudinal studies of adolescent smoking and drinking.
AB  - The principles that behavior is strongly influenced by the behavior of friends,
      and that people select each other to be friends on the basis of common
      characteristics, are based in large part on the many studies of adolescents that
      found the behavior of friends to be similar. In most of these studies, subjects
      were asked to describe, the behavior of their friends, and this information was
      then related to subjects' reports of their own behavior. The research on
      adolescent smoking and drinking described in this paper departs from that
      tradition by including friend reports of friend behavior so that results based on
      the different sources for measuring friend behavior can be compared. Subject
      report of friend behavior is a stronger correlate, of adolescent behavior than
      friend report of friend behavior, but the two sources for measuring friend
      behavior produce the same correlations with subject behavior when using
      longitudinal designs and controlling for prior subject behavior. The findings are
      discussed in the context of theoretical and methodological considerations of peer
      influence and selection. 

PMID- 24301834
TI  - Barbronia weberi (Clitellata, Hirudinida, Salifidae) has ovary cords of the
      Erpobdella type.
AB  - The organization of the ovaries in representative of the Salifidae (Hirudinida,
      Erpobdelliformes) was studied at the ultrastructural level for the first time.
      Like in other leeches, the ovaries of Barbronia weberi are composed of an outer
      envelope (i.e., an ovisac made up of two coelomic epithelia, muscle cells, and
      connective tissue) and several internal units, which are broadly similar to the
      ovary cords found in representatives of the Erpobdellidae. There are usually 6-8
      ovary cords that are twisted or cambered with a narrow apical part and a broader,
      irregularly shaped distal end in each ovisac of B. weberi. Each ovary cord is
      built from somatic and germ-line cells and the latter tend to form multicellular
      cysts that are equipped with a central cytoplasmic core (cytophore). There are
      two morphologically different subpopulations of germ-line cells: oocytes and more
      numerous nurse cells. Growing oocytes form protuberances on the ovary cord
      surface and eventually detach from the cord and float freely in the ovisac lumen,
      whereas the other components of germ-line cysts (i.e., nurse cells and cytophore)
      degenerate. It should be pointed out that there is a prominent gradient of germ
      cell development along the long axis of the cord. The somatic cells form the
      ovary cord envelope (the so-called spongiosa cells) and also penetrate the spaces
      between germ-line cells. Both kinds of the somatic cells, that is, those forming
      the cord envelope and the somatic cells that are associated with oocytes
      (follicular cells) have a well-developed system of intercellular channels.
      Additionally, one prominent somatic cell, the apical cell, was found at the
      apical tip of each ovary cord. Because the aforementioned features of ovary cords
      found in B. weberi are very similar (with a few minor exceptions) to the ovary
      cords that have been described in Erpobdella octoculata and E. johanssoni, we
      propose the term "ovary cords of the Erpobdella type" for them. Our results
      support a close phylogenetic relationship between Salifidae and Erpobdellidae.

PMID- 24301835
TI  - Searching for the rainbow's end.

PMID- 24301837
TI  - The emotional impact of treating child abuse.
AB  - The author agrees with the need for pastoral intervention in child abuse and
      neglect, but warns that pastors need to be prepared to handle the intense
      emotional effects that result. The emotional impact of treating child abuse and
      neglect is examined under the rubric "countertransference." Three sources of
      countertransference are outlined: identification with the child, identification
      with the parent, and encountering resistance. Finally, ways to cope with
      countertransference engendered by treating child abuse and neglect are explored.
      The need for quality supervision is especially stressed. 

PMID- 24301838
TI  - A gandhian model of health: Looking at Alzheimer's disease.
AB  - Mahatma Gandhi was often criticized for mixing religion, politics, economics, and
      health. However, it was his very insistence on the fundamental interrelationship
      of all aspects of life that gives his ideas such relevance for today's problems.
      This paper focuses on his views on health and attempts to develop a Gandhian
      model of health that has relevance for us today. This model is then specifically
      applied to the vexing problem of Alzheimer's disease, and an ongoing therapeutic
      trial that is based on this model is described. 

PMID- 24301839
TI  - Fear, faith, and movement.
AB  - This paper describes the intra-psychic dynamics associated with faith
      development. Using James Fowler's stages of faith theory, the author attempts to
      demonstrate that growth in faith requires courage in order to confront the loss
      of self experienced in faith development. Using the work of Hartmann, Mahler, and
      Kegan in conjunction with the thought of Tillich regarding fear and faith, the
      article presents a process for transition from Fowler's stage four to stage five
      which relies heavily upon the interaction of the self and others for successful
      movement. 

PMID- 24301836
TI  - Is there a religious factor in health?
AB  - This paper reviews epidemiologic studies employing religion as an independent
      construct, and finds that most epidemiologists have an extremely limited
      appreciation of religion. After a historical overview of empirical religion and
      health research, some theoretical considerations are offered, followed by
      clarification of several operational and methodological issues. Next, well over
      200 studies are reviewed from nine health-related areas: cardiovascular disease,
      hypertension and stroke, colitis and enteritis, general health status, general
      mortality, cancer of the uterine corpus and cervix, all other non-uterine
      cancers, morbidity and mortality in the clergy, and cancer in India. Finally, an
      agenda for further research is proposed. 

PMID- 24301840
TI  - Modifying the Type A behavior pattern.
AB  - The Type A behavior pattern (TABP), a complex of personality traits characterized
      by insecurity of status, hyperaggressiveness, sense of time urgency, free
      floating hostility, and a tendency toward self-destruction, has been linked to
      coronary heart disease in both prospective and clinical studies. Attempts to
      modify the TABP are complicated by conceptual understandings of the behavioral
      complex. However, intervention studies, such as the San Francisco Recurrent
      Coronary Prevention Project, have shown that modification is possible. Both
      psychological and religious factors need to be taken into consideration when
      exploring the modification of the TABP. 

PMID- 24301841
TI  - Exploratory study of black psychological health.
AB  - Three groups of black men and women (primarily student groups) participated in
      this exploratory study which was designed to help participants define
      psychological health or wellbeing for themselves. Spirituality and religion were
      cited as being primary components of psychological health for all groups.
      However, the results are only suggestive given the small number of subjects.
      Finally, I discuss a distinction between spirituality and religion, developmental
      implications, and the role of oppression in defining black psychological health. 

PMID- 24301842
TI  - Oncologist factors that influence referrals to subspecialty palliative care
      clinics.
AB  - PURPOSE: Recent research and professional guidelines support expanded use of
      outpatient subspecialty palliative care in oncology, but provider referral
      practices vary widely. We sought to explore oncologist factors that influence
      referrals to outpatient palliative care. METHODS: Multisite, qualitative
      interview study at three academic cancer centers in the United States with well
      established palliative care clinics. Seventy-four medical oncologists
      participated in semistructured interviews between February and October 2012. The
      interview guide asked about experiences and decision making regarding outpatient
      palliative care use. A multidisciplinary team analyzed interview transcripts
      using constant comparative methods to inductively develop and refine themes
      related to palliative care referral decisions. RESULTS: We identified three main
      oncologist barriers to subspecialty palliative care referrals at sites with
      comprehensive palliative care clinics: persistent conceptions of palliative care
      as an alternative philosophy of care incompatible with cancer therapy, a
      predominant belief that providing palliative care is an integral part of the
      oncologist's role, and a lack of knowledge about locally available services.
      Participants described their views of subspecialty palliative care as evolving in
      response to increasing availability of services and positive referral
      experiences, but emphasized that views of palliative care as valuable in addition
      to standard oncology care were not universally shared by oncologists.
      CONCLUSIONS: Improving provision of palliative care in oncology will likely
      require efforts beyond increasing service availability. Raising awareness of ways
      in which subspecialty palliative care complements standard oncology care and
      developing ways for oncologists and palliative care physicians to collaborate and
      integrate their respective skills may help.

PMID- 24301844
TI  - Development of cyanide-resistant respiration in mitochondria from potato tubers
      treated with ethanol, acetaldehyde, and acetic acid.
AB  - Treatment of intact potato (Solanum tuberosum L.) tubers with acetaldehyde,
      ethanol or acetic-acid vapors led to a respiratory upsurge which was further
      increased when the volatiles were applied in 100% O2. Mitochondria from tubers
      held in 100% O2 (O2 control) displayed a substrate state, state 3, and state 4 in
      respiration, whereas in mitochondria from the volatile-treated tubers the
      respiratory rate of the different states was virtually indistinguishable. This
      respiratory pattern was companied by the development of a cyanide-resistant
      respiration since these mitochondria exhibited resistance to CN and sensitivity
      to CN+salicylhydroxamic acid. Acetaldehyde-treated potatoes showed a time-course
      development (up to 36 h) of cyanide resistance and concomitant sensitivity to
      salicylhydroxamic acid, indicating the onset of synthetic processes leading to
      the observed changes in mitochondrial respiration. 

PMID- 24301843
TI  - Review of electronic patient-reported outcomes systems used in cancer clinical
      care.
AB  - PURPOSE: The use of electronic patient-reported outcomes (PRO) systems is
      increasing in cancer clinical care settings. This review comprehensively
      identifies existing PRO systems and explores how systems differ in the
      administration of PRO assessments, the integration of information into the clinic
      workflow and electronic health record (EHR) systems, and the reporting of PRO
      information. METHODS: Electronic PRO (e-PRO) systems were identified through a
      semistructured review of published studies, gray literature, and expert
      identification. System developers were contacted to provide detailed e-PRO system
      characteristics and clinical implementation information using a structured review
      form. RESULTS: A total of 33 unique systems implemented in cancer clinical
      practice were identified. Of these, 81% provided detailed information about
      system characteristics. Two system classifications were established: treatment
      centered systems designed for patient monitoring during active cancer treatment
      (n = 8) and patient-centered systems following patients across treatment and
      survivorship periods (n = 19). There was little consensus on administration,
      integration, or result reporting between these system types. Patient-centered
      systems were more likely to provide user-friendly features such as at-home
      assessments, integration into larger electronic system networks (eg, EHRs), and
      more robust score reporting options. Well-established systems were more likely to
      have features that increased assessment flexibility (eg, location, automated
      reminders) and better clinical integration. CONCLUSION: The number of e-PRO
      systems has increased. Systems can be programmed to have numerous features that
      facilitate integration of PRO assessment and routine monitoring into clinical
      care. Important barriers to system usability and widespread adoption include
      assessment flexibility, clinical integration, and high-quality data collection
      and reporting.

PMID- 24301845
TI  - Partial purification of endo- and exo-beta-D-glucanase enzymes from Zea mays L.
      seedlings and their involvement in cell-wall autohydrolysis.
AB  - The proteins dissociated from isolated Zea seedling cell wall using high-ionic
      strength salt solutions have been found to include a number of enzymes which
      appear to participate in autolytic reactions of the cell wall. These enzymes
      caused extensive degradation of enzymatically inactive cell wall, liberating as
      much as 100 MUg/mg dry weight over a 48-h period. Lithium chloride (3M) was shown
      to be most effective in yielding protein and wall-degrading activities.Molecular
      sieve chromatography of the cell-wall protein resolved endo-beta-D-glucanase and
      exo-beta-1,3-glucanase (EC 3.2.1.58) activities when Avena glucan and laminarin,
      respectively, were employed as substrates. The exoenzyme (molecular weight around
      60,000) was strongly inhibited by inorganic mercury at a concentration which
      suppressed the release of monosaccharide from autolytically active cell wall. The
      endo-beta-D-glucanase (MW around 26,000), which showed a marked preference for
      substrates of mixed-linkage, exhibited features indicating that it initiates the
      autolytic solubilization of wall glucan.Cell-wall beta-D-glucan, recovered as a
      component of an alkali-soluble cell-wall fraction, served as a substrate for the
      purified glucanases. Their hydrolysis pattern, assessed using gel exclusion
      chromatography and product analysis, confirmed that they hydrolyze beta-D-glucan.
      The products generated by the endoglucanase were similar in molecular-size
      distribution to those liberated from autolytically active-wall. Exoglucanase
      activity was required for extensive hydrolysis of beta-D-glucan in vitro.During
      coleoptile development the autolytic activity of the cell wall increased
      dramatically. This increased activity, however, did not parallel the growth
      potential of the tissue, but more closely reflected an increase in cell-wall beta
      D-glucan, the primary substrate for autolytic reactions. 

PMID- 24301846
TI  - Evolution of the cytoplasmic organelles during female meiosis in Pisum sativum L.
AB  - In this paper we have traced the evolution of the cytoplasmic organelles in the
      female germinal cell of Pisum sativum L., from the beginning of meiosis to the
      early stages of the maturing megaspore, in order to correlate the morphological
      changes with the physiological aspects of megasporogenesis.A process of intense
      cytoplasmic vacuolation takes place in the megaspore mother cell (MMC) during
      prophase I, probably proceeding from the smooth endoplasmic reticulum and
      dictyosomes; it results in the formation of big vacuoles, which play a role in
      MMC polarization. By means of this polarization most plastids and mitochondria
      are incorporated into the functional megaspore at the end of meiosis.There are
      plastid and mitochondria cycles which consist of dedifferentiation followed by
      redifferentiation, During these cycles a transient morphology appears, called a
      cup-shaped form, which we interpret as an expression of low organelle
      activity.The wall of the MMC thickens throughout megasporogenesis and loses its
      plasmodesmata during middle prophase I. The ribosome population is reduced during
      prophase I and then restored during the early stages of the megaspore maturing
      process, as shown by the quantitative study that we have carried out. The
      nucleolar cytoplasmic bodies play a part in this restoring process. These bodies
      have a special morphology and appear to be originated from the activity of the
      nucleolar organizing region (NOR) during nucleolar disorganization in prophase
      I.We think that this cytoplasmic evolution is a response to nuclear genic
      recombination, in order to provide the most adequate expression of the zygote
      genome. 

PMID- 24301847
TI  - On the cellular localization of phosphoenolpyruvate carboxylase in Sorghum
      leaves.
AB  - The localization of phosphoenol pyruvate carboxylase (EC 4.1.1.3.1.) in the leaf
      cells of Sorghum vulgare was investigated by using three techniques: the
      conventional aqueous and non aqueous methods gave conflicting results; the
      immunocytochemical techniques clearly showed that the enzyme is predominantly
      located in the cytoplasm of mesophyll cells. 

PMID- 24301848
TI  - beta-1-3- and beta-1-4-glucan synthesis by membrane fractions from the fungus
      Saprolegnia.
AB  - The beta-glucan synthetase activity of the fungus Saprolegnia monoica was assayed
      by supplying UDP-glucose to membrane fractions of mycelial homogenate. The
      analysis of glucan products by hydrolysis with various beta-glucanases and by
      chromatography show that both beta-1-3- and beta-1-4-linkages are formed at high
      substrate concentrations. In the absence of MgCl2, beta-1-3-linked glucans are
      mainly produced. By increasing MgCl2 concentrations the total synthesis activity
      and beta-1-3-linkages production are reduced. At low substrate concentrations in
      the presence of MgCl2, beta-1-4-linked glucans are the only polysaccharide
      synthesized. Electron microscopy of radioactive products, synthesized by original
      membrane fractions or by membrane fractions isolated from continuous sucrose
      density gradients, shows microfibrils when the assays are conducted at high
      substrate concentrations in the absence of MgCl2. 

PMID- 24301849
TI  - Light activation of fructose bisphosphatase in isolated spinach chloroplasts and
      deactivation by hydrogen peroxide : A physiological role for the thioredoxin
      system.
AB  - Spinach chloroplast fructose bisphosphatase (EC 3.1.3.11.) exists in both
      oxidised and reduced forms. Only the latter has the kinetic properties that allow
      it to function at physiological concentrations of fructose 1,6-bisphosphate and
      Mg(2+). Illumination of freshly prepared type A chloroplasts causes a conversion
      of oxidised to reduced enzyme. The rate of this conversion does not limit the
      rate of CO2 fixation. In the dark the reduced enzyme partially reverts back to
      the oxidised form. If catalase is omitted from the reaction medium the rate of
      CO2 fixation by chloroplasts is decreased and seems to be limited by the rate of
      conversion of the enzyme to the reduced form. The physiological significance of
      the light dependent generation of dithiol compounds (such as thioredoxin) within
      chloroplasts is discussed. 

PMID- 24301850
TI  - Carotenoids in the outer cell-wall layer of Scenedesmus (Chlorophyceae).
AB  - Scenedesmus obliquus, strain 633, which synthesizes ketocarotenoids and
      sporopollenin, also forms pink-red-colored cell walls. Both the cell walls left
      over after autospore liberation and those from homogenates of disrupted green
      cells have similar carotenoid pigmentation. Canthaxanthin, astaxanthin, an
      unidentified ketocarotenoid, and lutein were found as integral cell wall
      components. They are bound to the outer (trilaminar) layer of the complete cell
      wall which also contains sporopollenin. 

PMID- 24301851
TI  - Ethylene formation by germinating, Drechslera graminea - Infected barley (Hordeum
      sativum) grains: A simple test for fungicides.
AB  - Grains of barley (Hordeum sativum L.); infected with the parasitic, systemic
      fungus Drechslera graminea, produce more ethylen than uninfected controls.
      Treatment of infected grains with mercury-free fungicides yields a differentiated
      suppression of the ethylene evolution 7 d after the beginning of germination.
      Suppression of visible symptoms (chlorotic stripes on leaves) appearing six to
      eight weeks after germination of infected, untreated seeds correlates with the
      decrease in ethylene formation after treatment with fungicides. The
      gaschromatographic ethylene determination thus allows for an early and reliable
      (significance higher than 99.9%) differentiation of fungicidal activities against
      the barley stripe disease. 

PMID- 24301852
TI  - Nitrogenase activity and dark CO2 fixation in the lichen Peltigera aphthosa
      Willd.
AB  - The lichen Peltigera aphthosa consists of a fungus and green alga (Coccomyxa) in
      the main thallus and of a Nostoc located in superficial packets, intermixed with
      fungus, called cephalodia. Dark nitrogenase activity (acetylene reduction) of
      lichen discs (of alga, fungus and Nostoc) and of excised cephalodia was sustained
      at higher rates and for longer than was the dark nitrogenase activity of the
      isolated Nostoc growing exponentially. Dark nitrogenase activity of the symbiotic
      Nostoc was supported by the catabolism of polyglucose accumulated in the ligh and
      which in darkness served to supply ATP and reductant. The decrease in glucose
      content of the cephalodia paralleled the decline in dark nitrogenase activity in
      the presence of CO2; in the absence of CO2 dark nitrogenase activity declined
      faster although the rate of glucose loss was similar in the presence and absence
      of CO2. Dark CO2 fixation, which after 30 min in darkness represented 17 and 20%
      of the light rates of discs and cephalodia, respectively, also facilitated dark
      nitrogenase activity. The isolated Nostoc, the Coccomyxa and the excised fungus
      all fixed CO2 in the dark; in the lichen most dark CO2 fixation was probably due
      to the fungus. Kinetic studies using discs or cephalodia showed highest initial
      incorporation of (14)CO2 in the dark in to oxaloacetate, aspartate, malate and
      fumarate; incorporation in to alanine and citrulline was low; incorporation in to
      sugar phosphates, phosphoglyceric acid and sugar alcohols was not significant.
      Substantial activities of the enzymes phosphoenolpyruvate (PEP) carboxylase (EC
      4.1.1.31) and carbamoyl-phosphate synthase (EC 2.7.2.5 and 2.7.2.9) were detected
      but the activities of PEP carboxykinase (EC 4.1.1.49) and PEP
      carboxyphosphotransferase (EC 4.1.1.38) were negligible. In the dark nitrogenase
      activity by the cephalodia, but not by the free-living Nostoc, declined more
      rapidly in the absence than in the presence of CO2 in the gas phase. Exogenous NH
      4 (+) inhibited nitrogenase activity by cephalodia in the dark especially in the
      absence of CO2 but had no effect in the light. The overall data suggest that in
      the lichen dark CO2 fixation by the fungus may provide carbon skeletons which
      accept NH 4 (+) released by the cyanobacterium and that in the absence of CO2, NH
      4 (+) directly, or indirectly via a mechanism which involves glutamine
      synthetase, inhibits nitrogenase activity. 

PMID- 24301853
TI  - Diurnal changes in the flux of calcium toward meristems and transpiring leaves in
      tomato and maize plants.
AB  - Tomato (Lycopersicon esculentum Mill. cv. Moneymaker) and maize (Zea mays L. cv.
      spec.) plants were supplied with (45)Ca-labeled nutrient solutions for a period
      of 8 or 16 h in the dark, in the light, or in a light-dark regime. Plant parts
      were analyzed for (45)Ca content. The partitioning of (45)Ca between mature
      leaves and meristems was shown to be affected by the presence of light. The
      transport of (45)Ca to meristems was higher in a dark period than in a comparable
      light period. Experiments with excised tomato shoots yielded similar distribution
      patterns of (45)Ca over leaves and meristems, thus excluding root pressure as the
      main driving force for the enhanced import of (45)Ca into the meristems in the
      dark. Results are discussed in terms of cation-exchange transport and competition
      between the various calcium sinks. 

PMID- 24301854
TI  - Dose responses for Colletotrichum lindemuthianum elicitor-mediated enzyme
      induction in French bean cell suspension cultures.
AB  - The induction of L-phenylalanine ammonialyase (PAL, EC 4.3.1.5) and flavanone
      synthase in French bean cell suspension cultures in response to heat-released
      elicitor from cell walls of the phytopathogenic fungus Colletotrichum
      lindemuthianum is highly dependent upon elicitor concentration. The elicitor dose
      response curve for PAL induction shows two maxima at around 17.5 and 50 MUg
      elicitor carbohydrate per ml culture, whereas the flavanone synthase response
      shows one maximum at around 100 MUg ml(-1). The PAL response is independent of
      the elicitor concentration present during the lag phase of enzyme induction; if
      the initial elicitor concentration is increased after 2 h by addition of extra
      elicitor, or decreased by dilution of the cultures, the dose response curves
      obtained reflect the concentration of elicitor present at the time of harvest.
      PAL induction is not prevented by addition of methyl sugar derivatives to the
      cultures; alpha-methyl-D-glucoside, itself a weak elicitor of PAL activity,
      elicits a multiphasic PAL response when increasing concentrations are added in
      the presence of Colletotrichum elicitor. Eight fractions with different
      monosaccharide compositions, obtained from the crude elicitor by gel-filtration,
      each elicit different dose-responses for PAL induction; the response to
      unfractionated elicitor is not the sum of the response to the isolated fractions.
      There is no correlation between the ability of the fractions to induce PAL in the
      cultures and their ability to act as elicitors of isoflavonoid phytoalexin
      accumulation in bean hypocotyls. 

PMID- 24301855
TI  - Photosynthesis and respiration of Griffithsia monilis (Rhodophyceae): Effect of
      light, salinity, and oxygen.
AB  - The giant-celled alga Griffithsia monilis has a low light compensation point and
      saturates photosynthesis at 60-90 MUmol photons m(-2)s(-1) (oxygen evolution and
      CO2 fixation). Under dark and low light intensities (14)C is preferentially
      incorporated into amino acids (mainly aspartate and alanine). With increasing
      light a gradual change was observed and, under light saturation, compounds of the
      anionic fraction (digeneaside and hexosephosphates) were the most strongly
      labeled compounds, together with the amino acids glycine and serine. To a large
      extent (30-40% of the total) (14)C was fixed into EtOH-insoluble products, the
      hydrolysates of which consisted mainly of glucose and mannose. In the steady
      state the rates of photosynthesis and respiration decreased with increasing
      salinity. Changes in the rates after hyperosmotic shocks were less severe in
      cells adapted to high salinities. Photorespiration exists in Griffithsia: Glycine
      and serine are the major labeled compounds in O2-saturated media. 

PMID- 24301856
TI  - Two routes for asparagine metabolism in Pisum sativum L.
AB  - Asparagine, a major transport compound, is metabolized in Pisum sativum by two
      enzymes, asparaginase (EC 3.5.1.1) and asparagine-pyruvate aminotransferase. The
      relative amount of the two enzymes varies between tissues. In developing seeds,
      there are very high levels of asparaginase but only trace amounts of the
      aminotransferase. Asparaginase is high in young leaves but falls rapidly during
      leaf growth; the aminotransferase remains high throughout development. Inhibitor
      studies with aminooxyacetate and methionine sulfoximine confirm that the
      aminotransferase is the main enzyme involved in asparagine utilisation in the
      leaf. Root tissue has low levels of asparaginase and only trace amounts of the
      aminotransferase. The asparaginase is potassium dependent, but is also partially
      activated by ammonium ions. The leaf aminotransferase has a lower K m for
      asparagine (4.5 mM) than the leaf asparaginase (8 mM). The seed asparaginase has
      a lower K m for asparagine (3 mM) than the leaf asparaginase. 

PMID- 24301857
TI  - Energy coupling for membrane hyperpolarization in Lemna: Evidence against an ATP
      fueled electrogenic pump as the exclusive mechanism.
AB  - The vacuolar electrical potential of Lemna paucicostata 6746 has an active
      component of about-130 mV. This hyperpolarization above the diffusion potential
      was maintained when dicyclohexyl carbodiimide (DCCD) or arsenate (0.1 mM or 5 mM
      final concentrations, respectively) were added in the light or after the plants
      had been kept in darkness for 1 h. The ATP level was reduced to 11+/-3% by DCCD
      and to 56+/-6% by arsenate under conditions identical to those during the
      potential measurements. In this report, it is discussed whether these results
      could be interpreted in terms of a putative electrogenic ATPase in the plasma
      membrane of Lemna. Rb(+)-influx in illuminated plants was 12.5% or 52% of the
      control when ATP generation was inhibited by DCCD or arsenate. This finding is
      regarded as justifying the assumption that the availability of ATP at plasmalemma
      located transport sites is drastically decreased by these inhibitors.A passive
      proton-permeability in the cell membrane was induced with different
      concentrations of carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The potential
      decrease, caused by the current through this shunt, was not affected by DCCD. It
      therefore seems less conceivable that the cell membrane remains hyperpolarized
      because of an increase of membrane resistance concomitant to the inhibition of
      the pump.The significance of respiratory processes for membrane hyperpolarization
      is displayed by the depolarizing action of anoxia or KCN. As ATP was found to be
      non-limiting under these conditions, the inhibition of the electrogenic pump is
      regarded as being in discord with the concept of an electrogenic ATPase, which is
      solely responsible for membrane hyperpolarization. 

PMID- 24301858
TI  - Using your bullets most wisely for the smoking gun.

PMID- 24301859
TI  - The experience of a multidisciplinary programme of pulmonary rehabilitation in
      primary health care from the next of kin's perspective: a qualitative study.
AB  - BACKGROUND: Pulmonary rehabilitation increases functional capacity and quality of
      life and decrease exacerbations in patients with chronic obstructive pulmonary
      disease (COPD), but there is little knowledge of how it influences their next of
      kin. AIMS: To describe the experience of a multidisciplinary programme of
      pulmonary rehabilitation in primary health care from the perspective of the next
      of kin. METHODS: A descriptive qualitative study was undertaken as part of a
      longitudinal study comprising a multidisciplinary programme for patients with
      COPD where the next of kin were invited to one session. Semi-structured
      interviews were conducted with 20 next of kin and analysed by qualitative content
      analysis. RESULTS: One main theme emerged - Life still remains overshadowed by
      illness. There were three sub-themes: a sense of deepened understanding; a sense
      of personal vulerability; and a sense of relief of burden. CONCLUSIONS: The next
      of kin's life was still overshadowed by illness, despite the multidisciplinary
      programme. Although experiencing positive outcomes two years after the programme,
      the next of kin expressed a need for more support. This study has shown that next
      of kin could benefit from their own participation and/or that of the patient in a
      multidisciplinary programme of pulmonary rehabilitation. We believe that next of
      kin should be offered primary health care support for the sake of their own
      health, but also in order to manage their informal caregiver role. The
      experiences described here could form a basis for further development of
      interventions for next of kin of patients with COPD.

PMID- 24301861
TI  - An approach to evaluating adolescent adaptive processes: Validity of an interview
      based measure.
AB  - The authors present an initial exploration, of the validity of 15 scales designed
      to assess adaptive ego processes in adolescence. These scales are rated solely. 

PMID- 24301862
TI  - Cognitive appraisal of major and daily stressful events during adolescence: A
      multidimensional scaling analysis.
AB  - Multidimensional scaling analysis was used to examine adolescents' cognitive
      appraisals of major and daily stressful events. The desirability of events was
      the only salient feature for early adolescents. Middle and late adolescents also
      appraised events in terms of their desirability; in addition, the amount of
      impact that events exerted on their lives and the generality of the causes of
      events were salient dimensions for these age groups. These results suggest
      increased complexity with age in adolescents' cognitive appraisals of stressful
      events. Correlational analyses also indicated that perceptions of personal coping
      capabilities are associated with high event desirability, high frequency of
      occurrence, stable causes, and decreased ability of others to be of help in
      coping. 

PMID- 24301863
TI  - Development of person description over adolescence.
AB  - Free-written descriptions of self and various others were obtained from 190
      adolescent boys and girls. Descriptions of persons became longer, more
      "psychological," and more organized over adolescence. Modes of construing persons
      were positively correlated across different stimulus persons. Selfdescriptions
      tended to be more person-centered than descriptions of others. However, more
      dispositional terms were ascribed to others than to the self. In contrast with
      previous research, substantial sex differences were found. Girls had more to say
      about persons and this was expressed more in psychological terms; girls qualified
      and organized descriptions more than did boys. 

PMID- 24301864
TI  - The stress of secondary school for vulnerable students.
AB  - An assessment of the stress of junior high/middle school (JH/MS) can be made by
      comparing overall behavior and academic student patterns in JH/MS with those in
      elementary school (ES), and by evaluating the differential educational
      consequences experienced by JH/MS students who had varying degrees of
      maladjustment in ES. Specific numeric data indicate that the environment is far
      more open, combative, frightening, impersonal, and academically taxing in JH/MS
      than in the ES. Partly as a result, suspensions, unexcused absenteeism, and grade
      failure occur at a much greater overall rate in JH/MS. Also, the immediate
      aftermath of these school adversities is significantly more deleterious in JH/MS
      than in ES. An analysis of the differential outcome data reveals that JH/MS
      students who had prominent ES maladjustments have a 5-13-fold greater rate of
      grade failure, suspension, and undue absenteeism than do students without such ES
      difficulties, and that generally students without major ES malajustment patterns
      continue to perform well after their entry to secondary school. In effect, then,
      JH/MS is primarily a stressful environment for students who are vulnerable on
      entry. 

PMID- 24301865
TI  - Development of a self-report measure of adherence for children and adolescents
      with insulin-dependent diabetes.
AB  - Two samples of insulin-dependent diabetic youths were studies in successive
      attempts to refine a brief patient self-report measure of general long-term
      adherence to a diabetic regimen. Validity and reliability were assessed for both
      samples by measuring a number of related variables: locus of control, stressful
      life events, knowledge of diabetes, parent report, and glycosylated hemoglobin.
      Initial evidence of validity was demonstrated in a variety of criterion areas.
      Both reliability and validity were replicated on the second sample. Adherence is
      discussed as a complex multidimensional variable, the measurement of which
      requires several different methods, including the selfreport measure described
      here. Warnings about social desirability as a confounding factor were discussed,
      as were suggestions for other adherence measures. 

PMID- 24301866
TI  - The learning disabled adolescent: Eriksonian psychosocial development, self
      concept, and delinquent behavior.
AB  - Using a developmental perspective, this study contrasted learning and nonlearning
      disabled adolescents on three variables: Erikson's stages of psychosocial
      development, self-concept, and delinquent behavior. It was predicted that
      learning disabled adolescents would show significantly less resolution of
      Erikson's fourth state, "industry versus inferiority," manifest lower overall
      self-concept, and report more delinquent behavior than their nondisabled peers.
      The results indicated that the learning disabled subjects, due to years of
      failing at school tasks, were unable to develop a sense of industry and
      competence. While these adolescents felt unpopular and inferior about their
      academic skills, the overall self-concept of the learning disabled sample was not
      significantly different than that of the comparison subjects. Finally, among
      nonadjudicated youths, learning disability was not found to be significantly
      associated with juvenile delinquency. Taken together, the results of this study
      show the utility of a developmental framework for a better understanding of the
      psychosocial adjustment of adolescents with learning handicaps. 

PMID- 24301867
TI  - Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the
      Brain.
AB  - Manipulation of gene expression in the brain is fundamental for understanding the
      function of proteins involved in neuronal processes. In this article, we show a
      method for using small interfering RNA (siRNA) in lipid nanoparticles (LNPs) to
      efficiently silence neuronal gene expression in cell culture and in the brain in
      vivo through intracranial injection. We show that neurons accumulate these LNPs
      in an apolipoprotein E-dependent fashion, resulting in very efficient uptake in
      cell culture (100%) with little apparent toxicity. In vivo, intracortical or
      intracerebroventricular (ICV) siRNA-LNP injections resulted in knockdown of
      target genes either in discrete regions around the injection site or in more
      widespread areas following ICV injections with no apparent toxicity or immune
      reactions from the LNPs. Effective targeted knockdown was demonstrated by showing
      that intracortical delivery of siRNA against GRIN1 (encoding GluN1 subunit of the
      NMDA receptor (NMDAR)) selectively reduced synaptic NMDAR currents in vivo as
      compared with synaptic AMPA receptor currents. Therefore, LNP delivery of siRNA
      rapidly manipulates expression of proteins involved in neuronal processes in
      vivo, possibly enabling the development of gene therapies for neurological
      disorders.Molecular Therapy-Nucleic Acids (2013) 2, e136;
      doi:10.1038/mtna.2013.65; published online 3 December 2013. 

PMID- 24301870
TI  - Variations on an old theme.

PMID- 24301871
TI  - Physicians and clergy in dialogue.
AB  - The goals and ends of contemporary medicine are often unclear. An explicit
      inquiry into the religious dimensions of healing offers an important perspective
      from which to evaluate the potential capabilities of the medical profession. This
      paper describes a course in which medical students joined divinity students to
      explore areas of mutual intellectual, professional, and personal interest.
      Students and faculty examined in depth three broad areas in which medicine and
      religion share common ground: concepts of health and illness from the religious
      perspective, approaches to the understanding of suffering and meaning, and the
      shared professional stresses of physician and clergy. 

PMID- 24301868
TI  - Promoter Targeting shRNA Suppresses HIV-1 Infection In vivo Through
      Transcriptional Gene Silencing.
AB  - Despite prolonged and intensive application, combined antiretroviral therapy
      cannot eradicate human immunodeficiency virus (HIV)-1 because it is harbored as a
      latent infection, surviving for long periods of time. Alternative approaches are
      required to overcome the limitations of current therapy. We have been developing
      a short interfering RNA (siRNA) gene silencing approach. Certain siRNAs targeting
      promoter regions of genes induce transcriptional gene silencing. We previously
      reported substantial transcriptional gene silencing of HIV-1 replication by an
      siRNA targeting the HIV-1 promoter in vitro. In this study, we show that this
      siRNA, expressed as a short hairpin RNA (shRNA) (shPromA-JRFL) delivered by
      lentiviral transduction of human peripheral blood mononuclear cells (PBMCs),
      which are then used to reconstitute NOJ mice, is able to inhibit HIV-1
      replication in vivo, whereas a three-base mismatched variant (shPromA-M2) does
      not. In shPromA-JRFL-treated mice, HIV-1 RNA in serum is significantly reduced,
      and the ratio of CD4(+)/CD8(+) T cells is significantly elevated. Expression
      levels of the antisense RNA strand inversely correlates with HIV-1 RNA in serum.
      The silenced HIV-1 can be reactivated by T-cell activation in ex vivo cultures.
      HIV-1 suppression is not due to offtarget effects of shPromA-JRFL. These data
      provide "proof-of principle" that an shRNA targeting the HIV-1 promoter is able
      to suppress HIV-1 replication in vivo.Molecular Therapy-Nucleic Acids (2013) 2,
      e137; doi:10.1038/mtna.2013.64; published online 3 December 2013. 

PMID- 24301872
TI  - The birth and death of religious leaders.
AB  - The phenomenon of religious leadership is a complex one. This article proposes
      that Ernest Becker's insight into the human tendency to deny death contributes to
      a better understanding of both the psychological and sociological dimensions of
      religious leadership. Specifically, it examines the role of transference in the
      leader-follower relationship and probes how this mechanism promotes the birth and
      demise of religious leaders. Some practical suggestions for healthy leader
      follower relations are offered. 

PMID- 24301873
TI  - Church youth alcohol and drug education programs.
AB  - This study indicates that pastors believe that their churches should have a role
      in influencing the alcohol and drug use of their members; that about half of the
      churches in this study actually had youth alcohol and drug education programs;
      and that the content of these education programs and church attitudes toward
      substance use are affected by the degree of fundamentalism-liberalism of the
      church. 

PMID- 24301874
TI  - Magician accuses faith healers of hoax.
AB  - Discussions of faith healing have traditionally focused on the persuasiveness of
      the healer and the receptivity of the audience. Recently magician James Randi
      investigated popular American faith healers and accused them of deliberate fraud.
      The deceptions he identified are those used for many years by fraudulent mediums
      and psychics. This paper reviews the history of conflict between charlatans and
      magicians, providing a context for understanding the findings of Randi. 

PMID- 24301875
TI  - Spiritual discernment in psychiatric patients.
AB  - The author uses resources from the Christian tradition of discernment of spirits
      to provide clinicians with guidelines for distinguishing the authentic and
      pathological aspects of religion in psychiatric patients. 

PMID- 24301876
TI  - The Jesus delusion: A theoretical and phenomenological look.
AB  - The delusion of being Jesus Christ is examined theoretically with respect to
      etiology and purpose. An interview with a person who had this delusion for two
      years conveys the raw experience of living the Jesus delusion. 

PMID- 24301877
TI  - Sex, sin, and the church: The dilemma of homosexuality.
AB  - A parallel is suggested between the way blacks have been treated in this country
      with the way some people view homosexuality. A critique of the origins of the
      homosexuality taboo and of the argument that homosexual persons are uniquely
      pathological follows. Though the Judeo-Christian tradition seems to have played a
      negative role in the past, the contemporary church, in concert with other
      institutions, can generate a moral force to help overcome homophobia. 

PMID- 24301878
TI  - Some stages of grief.
AB  - Does grief progress through stages? Do all people go through the same
      experiences? What health considerations are present in each grief experience?
      Does religion help? Although all people do not go through the same stages nor do
      they progress at the same rate, many people do go through such stages as the
      following: shock, lamentations, withdrawal, frustration, panic, depression,
      detachment, adaptation, reinvestment, and growth. There is often an interaction
      in these stages between stress and physical symptoms, and many grievers report
      that religion gives a good philosophical arean in which to work through their
      grief. 

PMID- 24301879
TI  - Pastoral counseling and petitionary prayer.
AB  - Petitionary prayer is a valid and often-used form of prayer among religious
      people. Not infrequently, pastoral counselors find themselves praying for
      clients. This article explores the pastoral counselor's use of petitionary
      prayer, experientially and theologically, and attempts to locate its meaning
      within the healing enterprise. 

PMID- 24301880
TI  - Skid-row rescue missions: A religious approach to alcoholism.
AB  - The focus of this study is on the religious service at which many skid-row rescue
      missions require attendance to receive benefits. Data were obtained from an
      observation study of thirty-seven skid-row rescue missions in Los Angeles and
      Seattle, interviews with ten mission directors, and mission newsletters. The
      missions use material benefits to attract potential converts. The theme of
      spiritual conversion is predominant in the mission service (sermons, songs,
      testimonies). Mission personnel feel they have been called by God, often have
      backgrounds similar to the people they serve, and view the skid rowers' problems
      as primarily personal and spiritual. Skid rowers resent the use of religion as
      bait, view their problems as primarily structural, and use the missions only as a
      last resort. The missions need to be compared to other alcoholism rehabilitation
      and religious institutions. A key component to their continued existence is
      outside Christian supporters. 

PMID- 24301881
TI  - Core size dependent hole transfer from a photoexcited CdSe/ZnS quantum dot to a
      conductive polymer.
AB  - Photoinduced hole transfer from a CdSe/ZnS quantum dot to a conjugated polymer is
      tuned by varying the quantum dot core size. Hole transfer affects the
      photoluminescence blinking of the quantum dot, increasing the duration of the on
      states and decreasing that of the off-states. 

PMID- 24301882
TI  - Photoelectrical properties of insulating LaAlO3-SrTiO3 interfaces.
AB  - We report photoconductivity of an insulating LaAlO3-SrTiO3 (LAO-STO)
      heterointerface. Persistent photocurrent induced by a 514 nm laser at room
      temperature is significant, which is attributed to carriers trapped by a built-in
      potential well at the interface. Further studies of photoconductivity of the
      insulating LAO-STO interface performed with a monochrometer demonstrate the
      photoelectrical response not only in the ultraviolet region but also in the
      visible and infrared regions. The extrinsic photoconductivity indicates several
      midgap states located in the insulating LAO-STO interface. Our results provide a
      deep understanding of the band structure of the insulating LAO-STO
      heterointerface and promising applications as optoelectronic devices. 

PMID- 24301883
TI  - Identification of trail pheromone of larva of eastern tent caterpillarMalacosoma
      americanum (Lepidoptera: Lasiocampidae).
AB  - Previous studies have shown that larvae of the eastern tent caterpillar
      (Malacosoma americanum F.) mark trails, leading from their tent to feeding sites
      on host trees, with a pheromone secreted from the posterior tip of the abdominal
      sternum. 5beta-Cholestane-3,24-dione (1) has been identified as an active
      component of the trail. The larvae have a threshold sensitivity to the pheromone
      of 10(-11) g/mm of trail. Several related compounds elicit the trail-following
      response. Two other species of tent caterpillars also responded positively to the
      pheromone in preliminary laboratory tests. 

PMID- 24301884
TI  - Isolation, characterization and activity of phytotoxic compounds from quackgrass
      [Agropyron repens (L.)Beauv].
AB  - Previous experiments showed that legumes grown in the presence of living or
      herbicidally treated quackgrass residues or extracts exhibited reduced seedling
      root and shoot growth and decreased nodulation and nitrogen fixation. Aqueous
      extracts of quackgrass shoots were most inhibitory to plant growth. Upon
      sequential partitioning of an aqueous extract of quackgrass shoots, the ether
      extract possessed the most activity and caused 50% reductions in radicle
      elongation of eight crop and weed species at concentrations of less than 240
      MUg/ml (small-seeded species) and 1000 MUg/ml (large-seeded species). Snapbeans
      (Phaseolus vulgaris L. "Bush Blue Lake") grown aseptically in agar containing an
      ether extract at 100 and 200 MUg/ml exhibited severe root browning, lack of root
      hair formation, and a two- to three-fold reduction in root and shoot dry weights.
      The ether extract of quackgrass shoots had no inhibitory effect on the growth of
      fourRhizobium species in Petri dishes or two species in broth culture. Inhibitors
      present in the ether extract may influence the legumeRhizobium symbiosis
      indirectly by reducing legume root growth and root hair formation. The ether
      extract of quackgrass shoots was separated using high-pressure liquid, thin
      layer, and liquid column chromatography in an attempt to isolate and identify the
      inhibitors responsible for the inhibition of seedling growth. Two closely related
      flavonoid inhibitors were isolated from the ether extract. One was identified as
      5,7,4'-trihydroxy-3',5'-dimethoxyflavone (tricin). Both flavonoids caused 50%
      inhibition of radicle elongation in cress (Lepidium sativum L. "Burpee curly")
      seeds at concentrations of less than 125 MUg/ml. Both flavonoids were found in
      ether extracts of quackgrass shoots and rhizomes, but the largest amounts of both
      compounds occurred in quackgrass shoots collected from the field. 

PMID- 24301885
TI  - Microsomal oxidation of allelochemicals in generalist (Spodoptera frugiperda) and
      semispecialist (Anticarsia gemmatalis) insect.
AB  - Midgut microsomes prepared from larvae of the fall armyworm [Spodoptera
      frugiperda (J.E Smith)], a generalist insect, and the velvetbean caterpillar
      (Anticarsia gemmatalis Hubner), a semispecialist, were used to study their
      oxidative activity toward a variety of allelochemicals. Allelochemicals such as
      terpenoids, alkaloids, indoles, glucosinolates, flavonoids, coumarins,
      cardenolides, phenylpropenes, and a ketohydrocarbon were all metabolized by the
      microsomal cytochrome P-450 monooxygenases in both species. Fall armyworm
      microsomes oxidized monoterpenes more favorably than other types of terpenes,
      indicating a preference for these compounds. In all instances, the oxidative
      metabolism of these allelochemicals can be induced by dietary allelochemicals
      such as indole 3-carbinol, indole 3-acetonitrile, menthol, flavone, or peppermint
      oil ranging from 1.3- to 9.5-fold. In the case of certain triterpenes,
      tetraterpene, alkaloid, coumarin, and cardenolides, metabolic activity can only
      be observed after induction. The monooxygenase activities toward these
      allelochemicals were generally higher in the generalist than in the
      semispecialist. These findings provide strong evidence that microsomal
      monooxygenases play an important role in the detoxification of plant toxins and
      hence host-plant selections in herbivorous insects. 

PMID- 24301886
TI  - Radial diffusion method for determining tannin in plant extracts.
AB  - Tannin in plant extracts can be determined by reacting the tannin with a protein
      and quantitating the precipitated complex. In the new assay described here, a
      tannin-containing solution is placed in a well in a protein-containing agar slab.
      As the tannin diffuses into the gel and complexes with protein, a visible ring of
      precipitation develops. The area of the ring is proportional to the amount of
      tannin in the extract. The detection limit of the method is 0.025 mg tannic acid
      or condensed tannin and the precision is 6% (relative standard deviation). Tests
      with extracts of a variety of plants show that the new method gives results
      comparable to other precipitation methods and that the new method is superior for
      samples of unusual composition, such as aspen buds. The method has several
      advantages over other methods for determining tannin: The new method is very
      simple and requires neither complex reagents nor instruments. Components of the
      plant extract such as non-tannin phenolics or water-insoluble compounds do not
      interfere with the method. The assay is not subject to interference from the
      organic and aqueous solutions which are commonly used to extract tannin from
      plants. 

PMID- 24301887
TI  - Ester and ketone components of aggregation pheromone ofDrosophila hydei (Diptera:
      Drosophilidae).
AB  - Existence of an aggregation pheromone inDrosophila hydei was demonstrated by
      laboratory bioassay. The pheromone was produced by mature males, but both sexes
      responded. The nonpolar components consisted of three esters: the methyl, ethyl,
      and 1-methylethyl (isopropyl) esters of 2-methyl-(E)-2 butenoic (tiglic) acid,
      and two ketones: 2-tridecanone and 2-pentadecanone. The ketones and esters alone
      were only minimally active in the laboratory bioassay, but 2-tridecanone was
      highly synergistic with each of the esters, mixtures attracting 3-60 times more
      flies than the single components. 2-Pentadecanone was less active, but it did
      cause significant increases in activity when added to synthetic mixtures. The
      nonpolar portion of an extract of mature males and an equivalent mixture of the
      synthetic components were not significantly different in bioassay. Neither the
      esters nor the ketones were detected in sexually immature males or in females of
      any age. In extracts of mature males, ethyl tiglate was usually the most abundant
      ester component, with a mean of 8 +/- 5 (SD) ng/male. The absolute and relative
      levels of the other esters were more variable. The mean level of methyl ketones
      in the extracts was 122 +/- 106 (SD) ng/male, of which 85-93% was 2-tridecanone. 

PMID- 24301888
TI  - Identification of volatile allelochemicals fromAmaranthus palmeri S. Wats.
AB  - Allelopathic volatiles associated with the weed Palmer amaranth (Amaranthus
      palmeri S. Wats.; AMAPA) were trapped on Tenax GC, thermally desorbed, and
      identified by gas chromatography-mass spectroscopy. Methyl ketones and alcohols
      (C4-C11) were the principal components of the volatiles mixture. Seedheads,
      stems, or roots were placed in a glass container and incubated at 31  degrees C
      (10 hr)/21  degrees C (14 hr) for three days prior to trapping the volatiles.
      Seedheads were rich in 2-heptanone which was consistently found, together with 2
      heptanol, in all AMAPA tissues. Vapors of authentic 2-heptanone and (+/-)-2
      heptanol at concentrations of 1 ppm or higher strongly inhibited the germination
      of onion and carrot and almost completely suppressed the germination of tomato
      and AMAPA seeds. 

PMID- 24301889
TI  - Flavonoid pigments in chalkhill blue (Lysandra coridon Poda) and other lycaenid
      butterflies.
AB  - Nine flavonoids, namely, kaempferol, kaempferol 7-rharanoside, kaempferol 3
      rhamnoside, kaempferol 3-glucoside, kaempferol 3-glucoside, 7-rhamnoside,
      quercetin 3-glucoside, quercetin 3,7-diglucoside, isorhamnetin 3-glucoside, and
      isorhamnetin 3,7-diglucoside, have been identified in the body and wings of the
      chalkhill blue butterflyLysandra coridon Poda. Flavonoids have also been found in
      15 of a further 17 lycaenid species examined. Analysis of the two-dimensional
      paper chromatographic flavonoid patterns and aglycone results has shown that the
      flavonoid content ofL. coridon and the other lycaenids is dependent on the
      flavonoid content of the larval diet. Differences in the flavonoid patterns ofL.
      coridon and its leguminous larval food plantsHippocrepis comosa, Anthyllis
      vulneraria, andLotus corniculatus, indicate that the ingested flavonoids are
      metabolized byL. coridon or its gut flora before sequestration. Despite the
      presence of fiavones, glycoflavones, and isoflavones in the larval food plant
      species, only flavonols are sequestered by the lycaenid species examined. The
      relationship between lycaenid butterflies and their larval food plants, and the
      possible role(s) of flavonoids in lycaenids has been discussed. Interactions
      between ants, plants, flavonoids, and myrmecophilous lycaenids have also been
      considered. 

PMID- 24301890
TI  - Intermale sexual effect elicited by volatile urinary ether extract inMicrocebus
      murinus (Prosimian, Primates).
AB  - The effect of volatiles of diethyl ether-extracted dominant male mouse lemur
      urine on conspeciflc testosterone plasma concentrations was determined in an
      apparatus permitting olfactory isolation of the experimental subjects. Two
      experimental groups were exposed to air odorized with either ether or aqueous
      extracts of dominant male urine, while a third group received nonodorant air.
      Testosterone concentrations were measured before, during, and after the period of
      stimulation. The group submitted to the lipid fraction of dominant urine (N = 15)
      showed a significant decrease in testosterone concentrations. In contrast, no
      difference was observed between the group submitted to the aqueous fraction (N =
      10) and the controls (N = 11). This physiological effect, which occurs in
      response to conditions of persistent stress, appears to be due to lipophilic
      components present in the urine of dominant males. The results are discussed in
      terms of the social structure of this primitive primate species. 

PMID- 24301891
TI  - Quantitative comparison of behavioral and neurophysiological responses of insects
      to odorants : Inferences about central nervous system processes.
AB  - A consistent pattern of relationships emerges from comparisons of insect
      electroantennograms, peripheral olfactory receptor neuron responses, and
      behavioral responses to quantified concentrations of odorants. One consistency is
      that all of the different response measurements can be described by stimulus
      response curves of the same form. Another is that the responses have
      characteristic groupings when they are plotted against odorant concentration. The
      pattern of relationships is exemplified in the responses ofTrichoplusia ni
      (Hubner),Heliothis zea (Boddie), andPlodia interpunctella (Hubner) to several
      pheromone components and analogs. To quantify the relevant stimulus parameters
      for the response comparisons, the emission rates of the stimulus delivery system
      were calibrated for several 12 to 17-carbon pheromone components. The stimulus
      response relationships determined forT. ni, H. zea, andP. interpunctella are
      combined with relationships reported for other insects in the literature, and
      applications are discussed for the interpretation of pheromone trapping and
      laboratory bioassays. 

PMID- 24301892
TI  - Modification of olfactory-related behavior in juvenile Atlantic salmon by changes
      in pH.
AB  - The hypothesis that low pH modifies the response of salmonids to certain
      olfactory stimuli was tested. An interactive video-computer system was used to
      monitor the behavior of juvenile Atlantic salmon (Salmo salar). At a pH of 7.6,
      animals were attracted to glycine and avoidedL-alanine. These effects were dose
      dependent, with a threshold of 10(-7) M. The response of the fish to both amino
      acids changed when the pH of the test chamber was gradually lowered from 7.6 to
      5.1; they became attracted toL-alanine and indifferent to glycine. These effects
      were reversible with a return to pH 7.6. Our findings suggest that acid rain may
      contribute to reductions in salmonid populations in acidified rivers by impairing
      the recognition of olfactory cues by salmon during their spawning migration. 

PMID- 24301893
TI  - Stereoisomers and analogs of 14-methyl-1-octadecene, sex pheromone of peach
      leafminer moth,Lyonetia clerkella, L.
AB  - The synthesis of the enantiomeric 14-methyl-1-octadecenes in >99% EE is
      described. Enantiomeric 2-methyl-1-hexanols were intermediates in the synthesis.
      The 1-alkene had been previously identified as the sex pheromone of the peach
      leafminer moth. Several closely related structures that have delta12 unsaturation
      are also described. 

PMID- 24301894
TI  - Methodological approach to identify chemical oviposition stimulants from maize
      for European corn borer.
AB  - The noncontingent distribution ofO. nubilalis Hbn. eggs on various corn varieties
      has allowed their classification as either "favorable" or "nonfavorable" hybrids.
      This classification is based on a chemical communication system using volatile
      compounds active at a distance from the insect or active when in contact with the
      insect as soluble sugar components. Under this hypothesis, gas chromatography is
      the best way of investigating for the chemical differences between corn silk
      extracts from the two types of hybrids. A first experiment, using a "desorption
      trapping" system on Tenax coupled to a gas chromatograph showed a quantitative
      difference between two compounds from the two hybrids. A second experiment showed
      the advantages and disadvantages of this method and allowed the development of
      two complementary techniques: (1) direct extraction of corn silk with
      trichlorofluo-romethane and direct injection into a capillary column with an
      apolar stationary phase using an "on-column" system; and (2) extraction under
      vacuum of volatile compounds from corn silk and their trapping on Tenax, followed
      by a second desorption. This allows a direct injection on the same capillary
      column. The first technique allows identification by mass spectrometry of many
      alkanes with high molecular weights. The second technique seems to confirm the
      presence of phenylacetaldehyde. Both techniques show quantitative differences in
      the composition of corn silk extracts from "favorable" and "nonfavorable"
      hybrids; however, the biologically active chemicals remain unknown. 

PMID- 24301895
TI  - Variation in methylglucosinolate and insect damage toCleome serrulata
      (Capparaceae) along a natural soil moisture gradient.
AB  - We tested the hypothesis that plant loss to insects, and thus the relative
      fitness of an annual, was inversely related to spatial variation in the
      concentration of its characteristic secondary compound, methylglucosinolate, a
      mustard oil precursor. We found that methylyglucosinolate concentrations
      decreased significantly and linearly from the dry to the wet end along short soil
      moisture gradients in dry shortgrass prairie. Both leaf damage and capsule
      predation increased from the dry to the wet end. Thus, the glucosinolate appears
      to function defensively. Plant growth and flower production were favored at the
      wet end of the gradient; yet plants in the wet portion of the gradient were also
      more vulnerable to significant insect damage. The net result was that seed
      production by individual plants after predation was actually greater in the
      drier, harsher half of the gradient. The outcome strongly suggests that
      environmentally related variation in secondary compound concentration along
      environmental gradients can mediate and influence host-plant population abundance
      and distribution. 

PMID- 24301896
TI  - Honeybee (Apis mellifera L.) queen feces: Source of a pheromone that repels
      worker bees.
AB  - When placed in a small observation arena with workers, most young virgin honeybee
      queens released fecal (hindgut) material during agonistic interactions with
      workers and with each other. On release of this material, workers moved to the
      sides of the arena and groomed themselves. Bioassays of virgin queen fecal
      material demonstrated that it contains pheromone that repels workers and
      stimulates grooming behavior. Pheromone was present only in the feces of virgin
      queens that were more than 24 hr old and less than 2 weeks old. Feces of 2- to 4
      day-old workers and virgin queens more than 2 weeks old did not elicit an
      avoidance response by workers. Moreover, the feces of young virgin queens had a
      strong fragrance, while that of older queens had a rancid odor and that of young
      workers had no detectable odor. 

PMID- 24301897
TI  - Light-dependent effects of alpha-terthienyl in eggs, larvae, and pupae of
      mosquitoAedes aegypti.
AB  - Alpha-terthienyl is toxic toAedes aegypti larvae in the dark, but its activity is
      much enhanced in the presence of ultraviolet light. The development of first
      instar larvae treated with alpha-terthienyl and ultraviolet light was followed
      until the emergence of adults. The LC50 value for first instars was about 0.002
      ppm. Practically all the larvae which survived 24 hr reached adulthood. Fourth
      instar larvae were also sensitive to photochemical treatment. When their
      development into adults was followed, the LC50 value was 0.45 ppm. Contrary to
      earlier reports, alpha-terthienyl was also phototoxic in pupae, but not when the
      adults were about to emerge. The LC50 value was ca. 0.06 ppm for pupae which were
      1 or 2 days old. This is the first example where the activity of a
      photoinsecticide has been demonstrated in pupae. Alpha-terthienyl did not affect
      the hatching of eggs. 

PMID- 24301898
TI  - Failure of tannic acid to inhibit digestion or reduce digestibility of plant
      protein in gut fluids of insect herbivores : Implications for theories of plant
      defense.
AB  - The rate of hydrolysis of the abundant foliar protein, ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBPC), in enzymatically active gut fluid ofManduca sexta
      larvae is very rapid and is unaffected by the presence of tannic acid, even when
      tannic acid is present in the incubation mixture in amounts in excess of the
      amount of RuBPC. When this protein is dissolved in the denatured gut fluids ofM.
      sexta larvae orSchistocerca gregaria nymphs, large amounts of tannic acid must be
      added to bring about the precipitation of significant quantities of protein. The
      ability of insect gut fluid to prevent the formation of insoluble tannin-protein
      complexes is due to the presence of surfactants. On the basis of our results and
      a review of the findings of other investigators, we argue that there is no
      evidence that tannins reduce the nutritional value of an insect's food by
      inhibiting digestive enzymes or by reducing the digestibility of ingested
      proteins and, further, that the failure of tannins to interfere with digestion is
      readily explained on the basis of well-documented characteristics of the
      digestive systems of herbivorous insects. In challenging the currently popular
      notion that tannins are digestibility-reducing substances, we do not challenge
      the general utility of either the apparency theory or resource availability
      theory of plant defense. In debating the merits of these two analyses of plant
      herbivore interactions, however, the demise of tannins as all-purpose, dose
      dependent, digestibility-reducing defensive substances must be taken into
      account. 

PMID- 24301899
TI  - Sex pheromone differences in populations of the brownheaded
      leafroller,Ctenopseustis obliquana.
AB  - Ctenopseustis obliquana females collected from Christchurch were found to produce
      a mixture of (Z)-5-tetradecenyl acetate and tetradecyl acetate in their sex
      pheromone gland, in contrast toC. obliquana from Auckland which produce an 80?20
      mixture of (Z)-8-tetradecenyl acetate and (Z)-5-tetradecenyl acetate. This
      identification has been made on the basis of instrumental and chemical analyses.
      Antennae of maleC. obliquana from Christchurch gave a maximal electroantennogram
      response to (Z)-5-tetradecenyl acetate. A field trapping program in Christchurch
      using combinations of synthetic (Z)-5-tetradecenyl acetate and tetradecyl acetate
      caughtCtenopseustis males equally well if the latter chemical was present or
      absent. No males were caught in traps baited with the Auckland-type pheromone. In
      Alexandra,Ctenopseustis males were caught in traps baited with Auckland-type
      pheromone and not in traps baited with Christchurch-type pheromone. This
      phenomenon is ascribed to the existence of sibling species within the describedC.
      obliquana. 

PMID- 24301900
TI  - Sex pheromone ofPlanotortrix species found on mangrove.
AB  - (Z)-5-Tetradecenyl acetate and tetradecyl acetate were identified as sex
      pheromone components of an unnamedPlanotortrix leafroller moth species found
      onAvicennia resinifera (mangrove). An equal mixture of the two compounds used as
      bait gave field trap catches at least as good as those baited with caged virgin
      females. Traps baited with the two chemicals caught malePlanotortrix moths in a
      mangrove swamp not previously found to host the unnamedPlanotortrix species.
      Adults of the unnamedPlanotortrix species and of the greenheaded
      leafroller,Planotortrix excessana are morphologically indistinguishable. The sex
      pheromone ofP. excessana has been found previously to be a mixture of (Z)-S
      tetradecenyl acetate and tetradecyl acetate, and this means that the two species
      may now be distinguished by sex pheromone differences. 

PMID- 24301901
TI  - Variation in relative quantities of airborne sex pheromone components from
      individual femaleEphestia cautella (Lepidoptera: Pyralidae).
AB  - The airborne sex pheromone components (Z,E)-9,12-tetradeca-dien-1-yl acetate and
      (Z)-9-tetradecen-1-y1 acetate from single calling females ofEphestia cautella
      (Walker) were trapped within glass capillary tubes and were measured by gas
      chromatography-mass spectrometry. Broad and similar distributions of relative
      quantities were found for a laboratory strain and three Australian field strains,
      and means differed strongly from those reported previously for this species. The
      overall mean proportion of the two components found for Australian females was
      88?12. The composition in individuals ranged from 63?27 to 97?3. The proportions
      for individuals appeared to vary slightly in a random fashion from day to day,
      and proportions for first-generation progeny were influenced by the maternal
      blend. 

PMID- 24301902
TI  - Partial chemical characterization of urinary signaling pheromone in tree shrews
      (Tupaia belangen).
AB  - Tree shrews of both sexes exhibit marking behavior ("chinning") in response to
      scent marks made by the urine of fertile male conspecifics. To isolate the
      effective odor components, the urine was fractionated by liquid-liquid extraction
      and TLC, and the fractions were tested by bioassay. The results show that
      chinning is elicited by several lipophilic urine fractions, which are more
      effective in combination than alone. To characterize the complex scent signal,
      the lipophilic extracts from urine of the two sexes were analyzed by GC-MS and
      compared. The GC profile of the males is distinguished by pyrazine compounds not
      detected in the profile of the females. The profiles of the sexes also differ
      with regard to several volatile monocarboxylic acids, which are present at higher
      concentrations in male than in female urine. More than 30 urine components have
      been identified. Synthetic equivalents of these urine components were bioassayed
      for effectiveness in eliciting chinning and compared with one another as well as
      with scent substances not normally present in tree-shrew urine. Strong chinning
      responses were elicited by (1) certain pyrazine compounds and (2) some
      monocarboxylic acids, when presented at the high concentrations specific to male
      urine. Marking behavior is usually not elicited by scent substances not contained
      in tree-shrew urine or by urine components common to mammals in general. The data
      so far available indicate that the male-specific scent signal of tree shrews is
      based less on a single unique component than on the qualitative and quantitative
      characteristics of a multicomponent mixture. In the bioassay, tree shrews of both
      sexes respond equally to the male specific substances by chinning. As the scent
      signal represented by these substances has a different meaning to males and
      females (rival or potential mate, respectively), chinning probably serves several
      different functions. 

PMID- 24301903
TI  - Optimisation of the critical medium components for better growth of Picochlorum
      sp. and the role of stressful environments for higher lipid production.
AB  - BACKGROUND: Coastal countries that suffer from a scarcity of water, such as
      Tunisia, have to cultivate marine microalgae on non-arable land in order to
      produce feedstock and overcome their demands of nutrition and energy. In this
      framework, a green microalga, CTM 20019, was isolated, identified as Picochlorum
      sp. and tested for its lipid production. RESULTS: The dry weight of Picochlorum
      sp. is composed of 163 g kg(-1) lipids, 225 g kg(-1) total sugars, 440 g kg(-1)
      proteins and 112 g kg(-1) ash rich in potassium, calcium, iron, magnesium and
      zinc. Gas chromatography-mass spectrometry analysis showed that the main fatty
      acids were palmitic acid (29%), linolenic acid (26.5%), linoleic acid (23.5%),
      hexadecatrienoic acid (11%) and hexadecadienoic acid (8.5%). As it is known that
      culture conditions greatly influence the composition of microalgae, the
      experiments were designed to optimise the composition of the medium in order to
      increase Picochlorum sp. growth from OD680nm = 0.53 to OD680nm = 2.2 and lipid
      accumulation from 163 g kg(-1) to 190 g kg(-1) . The highest lipid contents of
      570 and 585 g kg(-1) were achieved under phosphate starvation and sodium
      carbonate supplementation, respectively. Under these conditions, the fatty acid
      profile is dominated by mono-unsaturated and polyunsaturated acids, and is
      therefore suitable for aqua-culture feeding. However, under high salinity, growth
      and lipid synthesis are inhibited, and the fatty acids are saturate, and the
      product is therefore suitable for biodiesel. CONCLUSION: This high lipid content
      rich in essential fatty acids, omega-6 and omega-3, endorses this wild strain of
      Picochlorum sp. as a promising feedstock for aqua-culture and human nutrition or
      for the production of biodiesel. (c) 2013 Society of Chemical Industry.

PMID- 24301904
TI  - Plasma levels of soluble tumor necrosis factor receptors are associated with
      cognitive performance in Parkinson's disease.
AB  - Inflammatory mechanisms have been implicated in a series of neuropsychiatric
      conditions, including behavioral disturbances, cognitive dysfunction, and
      affective disorders. Accumulating evidence also strongly suggests their
      involvement in the pathophysiology of Parkinson's disease (PD). This study aimed
      to evaluate plasma levels of inflammatory biomarkers, and their association with
      cognitive performance and other non-motor symptoms of PD. PD patients and control
      individuals were subjected to various psychometric tests, including the Mini
      Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Beck's
      Depression Inventory (BDI). Biomarker plasma levels were measured by enzyme
      linked immunosorbent assay (ELISA). PD patients exhibited worse performance on
      MMSE and the programming task of FAB, and presented higher soluble tumor necrosis
      factor receptor (sTNFR) plasma levels than control individuals. Among PD
      patients, increased sTNFR1 and sTNFR2 concentrations were associated with poorer
      cognitive test scores. After multiple linear regression, sTNFR1 and education
      remained a significant predictor for FAB scores. Our data suggest that PD is
      associated with a proinflammatory profile, and sTNFRs are putative biomarkers of
      cognitive performance, with elevated sTNFR1 levels predicting poorer executive
      functioning in PD patients.

PMID- 24301905
TI  - Spectroscopic signatures of topological and diatom-vacancy defects in single
      walled carbon nanotubes.
AB  - The optical properties, including UV-vis spectra and resonance Raman profiles, of
      pristine and defected single-walled carbon nanotubes (SWCNTs) are computed using
      state-of-the-art time-dependent density functional theory (TDDFT) as implemented
      using the Liouville-Lanczos approach to linear-response TDDFT. The CNT defects
      were of the form of Stone-Wales and diatom-vacancies. Our results are in very
      good agreement with experimental results where defects were introduced into a
      part of defect-free CNTs. In particular, we show that the first and second pi-pi*
      excitation energies are barely shifted due to the defects and associated with a
      relatively small reduction in the maxima of the absorption bands. In contrast,
      the resonance Raman spectra show close to an order of magnitude reduction in
      intensities, offering a means to distinguish between pristine and defected SWCNTs
      even at low defect concentrations. 

PMID- 24301906
TI  - Identification of marker genes in diabetic wounds by DNA microarray study.
AB  - This study aimed to identify marker genes in diabetic wounds using a dataset
      based on a DNA microarray of dermal lymphatic endothelial cells, and our results
      provide a basic understanding of diabetic wounds through further study of these
      differentially expressed genes (DEGs). From the Gene Expression Omnibus database,
      we downloaded a gene expression microarray (GSE38396) that includes 8 samples: 4
      normal controls and 4 disease samples (type II diabetes). We then identified
      genes that were differentially expressed between normal and disease samples using
      packages in R language, constructed a protein-protein interaction (PPI) network
      and analyzed modules in the network. In addition, phylogenetic analysis was
      performed by MEGA to find the most conserved genes. Two hundred and thirteen
      genes were identified as being differentially expressed between normal and
      disease samples, and we constructed a PPI network that included 213 pairs of
      proteins. We then identified a module including 20 genes, the function of which
      was significantly enriched in wounding response. Lastly, the most conserved
      genes, CD44 and CCL5, were identified through phylogenetic analysis. In summary,
      we found differentially expressed marker genes, a wounding response-related
      module, and the most important genes CD44 and CCL5. Our findings suggest new
      approaches to therapies for diabetic wounds. 

PMID- 24301907
TI  - Study of candidate genes for dyslexia in Brazilian individuals.
AB  - Dyslexia or reading disability (RD) is the most common childhood learning
      disorder and a significantly heritable trait. Many recent studies have
      investigated the genetic basis of dyslexia, and several candidate genes have been
      proposed. Among these, DCDC2 and KIAA0319 have emerged as the strongest candidate
      genes for dyslexia; however studies have not provided uniformly supportive
      results. The aim of this study was to assess the contribution of proposed
      candidate genes to the molecular etiology of dyslexia in a Brazilian sample.
      Large deletions and duplications in the candidate genes DCDC2, KIAA0319, and
      ROBO1 were investigated in 51 dyslexic subjects. Furthermore, a family-based
      association study was performed to investigate whether associations observed in
      other populations with variants in the DCDC2 and KIAA0319 genes were reproducible
      in Brazilian dyslexic individuals. Our analysis did not detect any deletions or
      duplications in the genes studied, and we found no evidence that the allelic
      variants in the two candidate genes were significantly associated with RD in our
      sample. Our data do not support a role of the DCDC2/KIAA0319 locus in influencing
      dyslexia as a categorical trait. Given the genetic complexity of dyslexia, it is
      plausible that both genes contribute to an increased risk, but the relative
      influence of these 2 genes on RD varies in different study samples, and/or
      depends on analytical approaches. 

PMID- 24301908
TI  - miR-499A>G rs3746444 and miR-146aG>C expression and hepatocellular carcinoma risk
      in the Chinese population.
AB  - We conducted a case-control study of a possible association of miR-499A>G
      rs3746444 and miR-146aG>C rs2910164 with risk of hepatocellular carcinoma.
      Samples from 172 hepatocellular carcinoma patients and 185 cancer-free controls
      were collected from October 2008 to December 2011. PCR-RFLP analysis was
      performed to determine the polymorphisms in each individual. The MAFs of miR
      146aG>C and miR-499A>G in controls were similar to that known from the SNP
      database, and frequencies of genotypes in controls were in line with Hardy
      Weinberg equilibrium. We found that miR-499 AG was significantly associated with
      decreased risk for hepatocellular carcinoma when compared with miR-499 AA
      genotype (adjusted odds ration = 0.74, 95% confidence interval = 0.24-0.96).
      However, subjects carrying miR-146a GG had a non-significant 0.62-fold decreased
      risk of hepatocellular carcinoma. We did not find a significant association of
      miR-146aG>C rs2910164 and miR-499A>G rs3746444 polymorphisms with hepatocellular
      carcinoma risk in the Chinese population. Further investigations are warranted to
      clarify the relationship between miRNA polymorphisms and susceptibility to
      hepatocellular carcinoma risk in various ethnic populations. 

PMID- 24301909
TI  - The first assess of the haplotypes from COI gene sequences in species of
      spittlebugs (Cicadomorpha: Hemiptera) and aquatic true bugs (Gerromorpha and
      Nepomorpha: Hemiptera) in Brazil.
AB  - We made the first analysis of the COI gene sequences of 22 species of spittlebugs
      and aquatic true bugs sampled in Sao Paulo State (Brazil) and used this
      information to determine the variability within these groups. Considering each
      codon position, we observed that the third base was the most variable, and the
      first base was the most conserved. Among species, Mahanarva fimbriolata and Deois
      flavopicta had the greatest genetic distance (0.181), and Notozulia entreriana
      and Mahanarva sp had the smallest distance (0.055), with an average variation of
      0.119. In Gerromorpha, the greatest distance occurred between Halobatopsis
      platensis and Rhagovelia zela (0.401), while between Cylindrostethus palmaris and
      Brachymetra albinervis albinervis, the distance was only 0.187; the average value
      observed for the Gerromorpha was 0.265. In the Nepomorpha, the species Buenoa
      antigone antigone and Belostoma micantulum had the greatest genetic distance
      (0.337), while Martarega brasiliensis and B. a. antigone had the smallest
      (0.154). The average value observed for Nepomorpha was 0.203. In Cicadomorpha
      (Auchenorrhyncha) and Nepomorpha (Heteroptera), the COI gene has been conserved;
      however, it is still useful for characterization of the different taxa. COI
      analysis was unable to resolve some of the Gerromorpha groups. 

PMID- 24301910
TI  - Experimental evaluation of the reproductive quality of Africanized queen bees
      (Apis mellifera) on the basis of body weight at emergence.
AB  - There has been much speculation about which phenotypic traits serve as reliable
      indicators of productivity in queen honeybees (Apis mellifera). To investigate
      the predictive value of queen body weight on colony development and quality, we
      compared colonies in which queens weighed less than 180 mg to those in which
      queens weighed more than 200 mg. Both groups contained naturally mated and
      instrumentally inseminated queens. Colonies were evaluated on the basis of
      performance quality, growth rate, and queen longevity. We found that queen body
      weight was significantly correlated with fecundity and colony quality. Heavy
      queens exhibited the most favorable performance and colony quality. In contrast,
      naturally mated, with the opposite trend being obtained for light-weight queens.
      We found no statistically significant difference between instrumentally
      inseminated queens and naturally mated queens. Our results support the use of
      queen body weight as a reliable visual (physiological) indicator of potential
      colony productivity in honey bees to enhance genetic lines in genetic improvement
      programs. 

PMID- 24301911
TI  - Isolation and characterization of microsatellite DNA loci for wild Brassica
      juncea (Brassicaceae).
AB  - Wild Brassica juncea is a widespread weed in China with increasingly great impact
      on the yield of many crops. This study aimed to develop microsatellite markers
      for assessing the genetic diversity and population genetic structure of B.
      juncea, and to provide basic information for biological and chemical control of
      the weed. The compound microsatellite marker technique was used to develop
      markers for investigating population genetics of wild B. juncea. Twelve loci were
      obtained, each of which showed high polymorphisms when tested in two populations
      in Sichuan and Jiangsu Provinces. The number of alleles per locus ranged from 4
      to 27, with an average of 15.2 alleles per locus. The newly developed
      microsatellite loci will be informative for further investigations of the
      population genetics and evolutionary patterns of wild B. juncea. 

PMID- 24301912
TI  - Utility of hair shafts from study skins for mitochondrial DNA analysis.
AB  - The condition of mtDNA in hair shafts preserved in a museum was examined using 30
      study skins of masked palm civets, Paguma larvata (Viverridae), collected between
      1924 and 2011. Comparisons of extracts from fresh and burnt alum-fixed hair
      shafts showed that burnt alum, which is commonly used in taxidermy, had no
      harmful effect on the amount of total DNA and lengths of the mtDNA fragments.
      Burnt alum-fixed hair shafts had a tendency to develop a small degree of melanin
      hindering PCR amplification compared with fresh hair shafts, although that
      observation was not supported statistically (Wilcoxon signed-rank test, Z = 
      0.183, P = 0.855). However, the amount of total DNA decreased after preparation
      of specimen in an exponential relation (regression of log DNA amount with year,
      regression analysis, F = 7.065, P = 0.013). Nevertheless, the oldest specimen,
      collected in 1924, yielded 1341.5 ng of DNA per 100 hair shafts, which was
      sufficient for PCR amplification. In addition, the mtDNA fragment length and
      amount of melanin in the hair shaft were not significantly correlated with the
      passage of time after preparation (F = 0.244, P = 0.625 for mtDNA fragment
      length; F = 0.039, P = 0.845 for the amount of melanin). Therefore, hair shafts
      prepared and preserved by chemical treatment in museums are good sources of mtDNA
      and useful for genetic analysis. 

PMID- 24301913
TI  - Effects of cisplatin and panobinostat on human mesothelial (Met-5A) and malignant
      pleural mesothelioma (MSTO-211H) cells.
AB  - New therapeutic approaches are still needed for effective malignant pleural
      mesothelioma treatment. The use of classical chemotherapy agents in combination
      with newly developed molecules may shed light on new therapeutic approaches. We
      aimed to determine the efficacy of panobinostat, alone and in combination with
      cisplatin, on cell survival and mRNA expression of FOXO3A, CCND1, and CASP9 genes
      in both mesothelioma and healthy mesothelial cell lines. Cells were treated with
      1-100 uM cisplatin and 25-1000 nM panobinostat. Methylthiazol tetrazolium assays
      were performed to determine cell viability. mRNA expression levels of genes were
      analyzed with quantitative real-time polymerase chain reaction. Cisplatin and
      panobinostat exposure of the cells for 24 h resulted in decreased cell survival.
      The combined treatment was found to be more effective. No significant changes
      were observed with respect to CCND1 expression after exposure to agents alone or
      in combination. However, agents in combination resulted in upregulation of FOXO3A
      and CASP9 in MSTO-211H cells. Gene expression levels were not affected by any
      agents in healthy cells. Use of cisplatin in combination with new
      chemotherapeutic agents may reduce the toxic effects of cisplatin in normal cells
      and result in more effective removal of tumor cells. 

PMID- 24301914
TI  - Prognostic implication of molecular aberrations in cytogenetically normal acute
      myeloid leukemia patients receiving allogeneic hematopoietic stem cell
      transplantation.
AB  - Different molecular aberrations can be discriminated into certain prognostic
      subgroups in cytogenetically normal acute myeloid leukemia (CN-AML) patients but
      their impact on allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      remains controversial and studies from Asian populations are lacking. Forty-two
      adult non-M3 AML patients receiving allo-HSCT from 2002 to 2009 in southern
      Taiwan were retrospectively reviewed for survey, 23 (54.7%) of whom were CN-AML.
      NPM1, FLT3-ITD, and CEBPA were analyzed. After a median follow-up of 104 weeks
      (range, 8 to 384), patients in the good risk group (harboring either NPM1 or
      CEBPA mutation without concurrent FLT3-ITD) showed a borderline worse overall
      survival (OS) compared with the intermediate/poor risk group (P = 0.08).
      Interestingly, a poorer OS was found in patients with the CEBPA mutation (P =
      0.003) but not the NPM1 mutation (P = 0.96). No OS difference was found between
      patients with or without FLT3-ITD (P = 0.15). In patients receiving allo-HSCT at
      first remission, there was no significant OS benefit in the good risk group (P =
      0.33). In patients receiving allo-HSCT beyond first remission, disease status
      played a major role (P = 0.006), irrespective of molecular aberrations. Allo-HSCT
      in good risk patients should be carefully evaluated in Taiwanese, especially in
      patients with the CEBPA mutation. Conversely, allo-HSCT should be considered in
      first remission in patients with an intermediate/poor risk, where it may overcome
      the adverse impact of FLT3-ITD. Disease status remained a main issue in patients
      receiving allo-HSCT beyond first remission. 

PMID- 24301915
TI  - Overexpression of an alternative oxidase gene, OsAOX1a, improves cold tolerance
      in Oryza sativa L.
AB  - Low temperature is a major environmental stress in rice cultivating and
      production. The alternative oxidase 1 (AOX1) gene is potentially important for
      genetic engineering to increase cold adaptation. However, previous studies
      related to this effect have mostly focused on the dicot plants Arabidopsis and
      tobacco, whereas functional research on rice is limited. In this study, we cloned
      a rice predominant cold-response AOX1 gene, OsAOX1a. Transgenic rice plants with
      overexpression of OsAOX1a were obtained. We found that OsAOX1a overexpression
      could strongly enhance the cold growth of seedlings, especially with respect to
      root extension. However, growth between transgenic and control plants did not
      differ under normal conditions. Furthermore, the lipid peroxidation and ion
      leakage rate were determined after cold treatment in transgenic plants. Both
      factors were reduced by OsAOX1a overexpression, which revealed that OsAOX1a could
      reduce oxidative damage under cold stress. Taken together, our results suggested
      that overexpressing OsAOX1a could improve growth performance of rice under cold
      stress, which might be closely related to the reduction of reactive oxygen
      species generation and oxidative damage. 

PMID- 24301916
TI  - Preventive effect of tert-butylhydroquinone on scrotal heat-induced damage in
      mouse testes.
AB  - To investigate the effect of tert-butylhydroquinone (tBHQ) on scrotal heat
      induced damage in mice testes, 8-week-old mice were divided into 6 groups and
      administered with or without tBHQ through diet (10 mg/g), intraperitoneal
      injection (100 mg/kg body weight), or intratestis injection (12.5 mg/kg body
      weight), respectively. After single scrotal heat exposure (42  degrees C for 25
      min), trunk blood and testes were collected 48 h later. The testes from diet and
      intraperitoneal tBHQ-treated mice showed more compact interstitial cells and less
      germ cell loss in the seminiferous epithelium compared with their corresponding
      non-tBHQ groups. However, intratestis tBHQ treatment showed no marked difference
      relative to the non-treatment group. In addition, pre-treatment of tBHQ caused
      lower testosterone concentrations and reduced expression of cytochrome P450
      17alpha-hydroxylase/17,20-lyase (CYP 17) compared to the corresponding non-tBHQ
      groups. The results indicated that scrotal heat-induced structural damage was
      partly prevented by pre-treatment of tBHQ, which could be used as an effective
      antioxidant for preventing scrotal heat-mediated male infertility.

PMID- 24301917
TI  - Mendelian inheritance, genetic linkage, and genotypic disequilibrium at nine
      microsatellite loci of Cariniana legalis (Mart.) O. Kuntze.
AB  - Cariniana legalis is one of the largest tropical trees with a wide distribution
      in the Brazilian Atlantic rainforest. We investigated the Mendelian inheritance,
      genetic linkage, and genotypic disequilibrium at seven microsatellite loci
      specifically isolated for C. legalis, and at two previously developed
      heterologous microsatellite loci. Forty to 100 open-pollinated seeds were
      collected from 22 seed-trees in two populations. Using the Bonferroni correction,
      no remarkable deviations from the expected Mendelian segregation, linkage, or
      genotypic disequilibrium were detected in the nine loci studied. Only 3.7% of the
      tests were significant for investigations of the Mendelian proportions. On the
      other hand, only 2.8% of tests for linkage detection showed significance. In
      addition, among all pairwise tests used for investigating linkage disequilibrium,
      significance was found in 9.7% of the locus pairs. Our results show clear
      evidence that the nine simple sequence repeat loci can be used without
      restriction in genetic diversity, mating system, and parentage analyses. 

PMID- 24301918
TI  - Genetic diversity of locally adapted sheep from Pantanal region of Mato Grosso do
      Sul.
AB  - Sheep of the Pantaneiro breed and seven other breeds, raised in the State of Mato
      Grosso do Sul, Brazil, were genotyped using eight microsatellite loci. The aim of
      the present study was to determine the genetic variability, phylogenetic
      relationship, and patterns of gene introgression and miscegenation among the
      animals surveyed, to obtain information about the genetic structure of locally
      adapted sheep in Mato Grosso do Sul. A total of 195 animals were used for genetic
      analysis. The Pantaneiro breed had the largest average number of alleles/locus
      (9.25), and higher allelic richness (6.95), while the Dorper population had the
      lowest values for these parameters (4.88 and 3.86, respectively). Analysis of
      genetic distance values and genetic structure between populations made it
      possible to characterize these animals with regard to distinct genetic groups.
      Average expected heterozygosity ranged from 0.72 (Pantaneiro) to 0.55 (Dorper),
      while average observed heterozygosity ranged from 0.63 (White Dorper) to 0.54
      (Dorper). On the basis of the statistical parameters evaluated, it was possible
      to demonstrate that when compared to other populations, the Pantaneiro breed
      represented a reservoir of genetic diversity with rare and useful alleles for
      genetic improvement, emphasizing the importance of preserving the breed. 

PMID- 24301919
TI  - Development of microsatellite markers for the kelp grouper Epinephelus bruneus by
      454 pyrosequencing and transfer to related species.
AB  - The kelp or longtooth grouper (Epinephelus bruneus), which inhabits Eastern Asia,
      is the most economically important of 11 grouper species that inhabit the
      Southern Sea near Jeju Island in Korea. This species is listed as vulnerable by
      the International Union for the Conservation of Nature and Natural Resources
      because of a rapid decrease in its resources. We developed microsatellite markers
      for E. bruneus using the pyrosequencing technique for applications in resource
      management and aquaculture. In addition, we tested the cross-species
      transferability of the microsatellite markers in four species belonging to the
      Epinephelus genus. Among 66,452 simple sequence repeats, 64 loci containing more
      than eight CA or TG repeats were randomly selected for primer synthesis; 45
      primer sets (75.0%) produced polymerase chain reaction (PCR) products of 100-300
      bp and were selected as candidates. After primary testing with four E. bruneus
      fish, 28 polymorphic loci were selected as the final microsatellite markers, and
      23 sets showing clear amplification of polymorphic loci were used to analyze 71
      fish. These loci have allele numbers ranging from 2 to 23. Null alleles were
      detected at three loci, and three loci showed an excess of homozygotes in the
      Hardy-Weinberg equilibrium test. Of the three species used for cross-species
      transfer of these markers, Epinephelus moara showed the highest transferability
      (92.9%) and polymorphism (67.9%), followed by Epinephelus fuscoguttatus (75.0 and
      67.9%, respectively) and Epinephelus septemfasciatus (57.1 and 46.4%,
      respectively). These results suggested that these microsatellite loci should be
      valuable tools for population genetic studies of the species Epinephelus. 

PMID- 24301920
TI  - Genetic characterization of Mytilus coruscus and M. galloprovincialis using
      microsatellite markers.
AB  - Korean (hard-shelled) mussels (Mytilus coruscus) are an economically important
      endemic marine bivalve mollusk of Korea; yet, the population has rapidly declined
      because of overharvesting and habitat competition from the invasive Mytilus
      galloprovincialis species. The population structures of M. coruscus and M.
      galloprovincialis were analyzed by next-generation sequencing using 5
      microsatellite markers specifically developed for M. coruscus. M.
      galloprovincialis had an average of 5.4 alleles per locus (range = 2-10), with an
      average allelic richness of 4.9 per locus (range = 2.0-9.3). M. coruscus had an
      average of 5.7 alleles per locus (range = 2-13), with an average allelic richness
      of 5.2 per locus (range = 2.0-11.9). Excessive homozygosity was observed at 3
      loci, which was assumed to be due to the presence of null alleles at these loci.
      Pairwise multilocus FST estimates showed that the M. coruscus and M.
      galloprovincialis populations were clearly separated. Six populations of M.
      galloprovincialis from the western, eastern, and southern coast of Korea formed 2
      separate clusters, indicating that more than 2 populations of M.
      galloprovincialis have been introduced to the Korean Peninsula. Hybrids between
      M. coruscus and M. galloprovincialis were not identified, probably because of
      genetic differences or different habitat preferences. Further genetic information
      is required to perform selective breeding, population management, and restoration
      of M. coruscus. 

PMID- 24301921
TI  - Association of novel single-nucleotide polymorphisms of the vascular endothelial
      growth factor-A gene with high-altitude adaptation in yak (Bos grunniens).
AB  - Vascular endothelial growth factor-A gene (VEGF-A) is a key regulator of
      angiogenesis and an endothelial cell mitogen that plays an important role in high
      altitude adaptation. In this study, we detected 2 novel single-nucleotide
      polymorphisms (SNPs) of VEGF-A by screening for genetic variation in 700
      individuals of 3 domestic Chinese yak breeds--namely Gannan (GN), Datong (DT),
      and Tianzhu white (TZW)--using polymerase chain reaction-restriction fragment
      length polymorphism and DNA sequencing techniques. GN and DT yaks live at high
      altitude and TZW yaks live at low altitude on the Qinghai-Tibetan Plateau. SNP
      g.8430T>C is located in intron 4 of VEGF-A. SNP g.14853G>A is located in the 3'
      untranslated region of VEGF-A. Frequencies of the GA and AA genotypes and the A
      allele of SNP g.14853G>A observed in GN and DT yaks were significantly higher
      than that in TZW yaks (P < 0.01). No significant difference among the breeds was
      observed for SNP g.8430T>C. The frequency of haplotype TA was significantly
      higher (P < 0.01), whereas the frequency of TG (P < 0.01) was significantly lower
      in GN and DT yaks compared with that in TZW yaks. The 2 SNPs were in moderate
      linkage disequilibrium in GN and DT yaks, but not in TZW yaks. The fixation index
      (FST) pairwise value was significantly different among the breeds studied. The
      neutral test result indicated that the region between the 2 SNPs may have been
      subjected to positive or balancing selection, and the high-altitude hypoxia
      environment might be the main determinant for selection. These results suggest
      that VEGF-A might contribute to the high-altitude adaptability of yak.

PMID- 24301922
TI  - Genetic diversity and differentiation of exotic and American commercial cattle
      breeds raised in Brazil.
AB  - The Brazilian cattle population is mainly composed of breeds of zebuine origin
      and their American derivatives. Comprehensive knowledge about the genetic
      diversity of these populations is fundamental for animal breeding programs and
      the conservation of genetic resources. This study aimed to assess the
      phylogenetic relationships, levels of genetic diversity, and patterns of
      taurine/zebuine admixture among 9 commercial cattle breeds raised in Brazil.
      Analysis of DNA polymorphisms was performed on 2965 animals using the 11
      microsatellite markers recommended by the International Society of Animal
      Genetics. High genetic diversity was detected in all breeds, even though
      significant inbreeding was observed within some. Differences among the breeds
      accounted for 14.72% of the total genetic variability, and genetic
      differentiation was higher among taurine than among zebuine cattle. Of note,
      Nelore cattle presented with high levels of admixture, which is consistent with
      the history of frequent gene flow during the establishment of this breed in
      Brazil. Furthermore, significant genetic variability was partitioned within the
      commercial cattle breeds formed in America, which, therefore, comprise important
      resources of genetic diversity in the tropics. The genetic characterization of
      these important Brazilian breeds may now facilitate the development of management
      and breeding programs for these populations. 

PMID- 24301923
TI  - Aberrant gene expression profiles in hepatocellular carcinoma detected by
      microdissection.
AB  - The aim of this study was to identify genomic aberrations in hepatocellular
      carcinoma (HCC) by using laser capture microdissection (LCM) combined with
      microarray analysis. Samples were procured by LCM from HCC and patient-matched
      normal liver tissue surgically resected from 4 patients. RNA was isolated from
      the samples and reverse transcribed into cDNA. After 2-cycle linear amplification
      and 2-color fluorescent labeling, the cRNA was hybridized onto a whole genome
      microarray. All genes expressed in the normal and HCC samples were counted and
      analyzed. Differentially expressed genes were identified and the top 10 up and
      downregulated genes (totally 20 genes) were further evaluated. LCM was able to
      accurately capture 50-200 cells from HCC and control tissues. The microarray
      spectrum showed satisfactory detection of HCC-enriched genes. A total of 1361
      differentially expressed genes were identified, among which, 607 were upregulated
      and 754 were downregulated. Among the top 20 up and downregulated genes, 4 genes
      had not been documented in the literature as being differentially expressed in
      any tumors. Thus, LCM is an effective approach for identifying aberrantly
      expressed genes in HCC, and may lead to the discovery of biomarkers for
      diagnostic and therapeutic applications. 

PMID- 24301924
TI  - A generic plant RNA isolation method suitable for RNA-Seq and suppression
      subtractive hybridization.
AB  - A recently developed revolutionary approach to transcriptomics, RNA-Seq, and
      suppression subtractive hybridization are powerful tools for gene expression
      research. However, currently, the difficulty of isolating high-quality RNAs from
      plant tissues bearing abundant complex polysaccharides, polyphenolics, and
      secondary metabolites is a serious problem that not only limits the application
      of these technologies but also hinders studies dealing with RNA in general. We
      have developed a consistent protocol to prepare highly intact and pure RNAs from
      tissues of a variety of field-grown plant species, with high yields, in 2 to 3 h.
      Additionally, this method can be readily applied to mammalian, yeast, and
      bacterial cells. 

PMID- 24301925
TI  - Construction of single-chain variable fragment antibodies against MCF-7 breast
      cancer cells.
AB  - A phage display library of single chain variable fragment (scFv) against MCF-7
      breast cancer cells was constructed from C3A8 hybridoma cells. RNA from the C3A8
      was isolated, cDNA was constructed, and variable heavy and light immunoglobulin
      chain gene region were amplified using PCR. The variable heavy and light chain
      gene regions were combined with flexible linker, linked to a pCANTAB 5E phagemid
      vector and electrophoresed into supE strain of Escherichia coli TG1 cells. Forty
      eight clones demonstrated positive binding activity to MCF-7 breast cancer cell
      membrane fragments and the strongest of 48 clones was selected for analysis. The
      anti-MCF-7 library evaluated by SfiI and NotI digests demonstrated that anti-MCF
      7 scFv antibodies possess individual patterns that should be able to recognize
      distinct human breast cancer cells. The C3A8 scFv, with an apparent molecular
      weight of 32 kDa, showed high homology (99%) with single chain antibody against
      rice stripe virus protein P20. In summary, the anti MCF-7 scFv antibody can be
      used for pretargeting breast cancer for clinical diagnosis of patients; it also
      has potential for therapeutic applications. 

PMID- 24301927
TI  - Establishment and molecular characterization of a sweet potato germplasm bank of
      the highlands of Parana State, Brazil.
AB  - The sweet potato (Ipomoea batatas L.) is a crop of great importance in developing
      countries, as a food staple, for animal feed, and potentially for biofuel.
      Development of cultivars adapted to specific regions within these countries would
      be useful. To start a breeding program, the first step is the establishment of a
      germplasm bank. We initiated a sweet potato germplasm bank with accessions
      collected from the highlands of Parana State, Brazil. To establish this germplasm
      bank, we carried out numerous sweet potato-collecting expeditions in regions with
      an altitude above 700 meters in this region; 116 genotypes currently comprise
      this collection. The genetic diversity of this germplasm bank was estimated using
      inter simple sequence repeat (ISSR) markers. Polymorphic information content
      (PIC), marker index (MI), and resolving power (RP) were calculated to determine
      the viability of ISSR markers for use in sweet potato genetic studies. The
      correlation between PIC and MI (r(2) = 0.81) and between MI and RP (r(2) = 0.97)
      were positive and significant, indicating that ISSR markers are robust for sweet
      potato identification. Two ISSR primers, 807 and 808, gave the best results for
      all attributes, and thus could be used as representative ISSR primers for the
      genetic analysis of sweet potato. Cluster analysis and principal component
      analysis indicated high genetic variability (0.51 of similarity among all
      genotypes); genotypes collected from different counties grouped together. 

PMID- 24301926
TI  - Effect of inhibition of MEK pathway on 5-aza-deoxycytidine-suppressed pancreatic
      cancer cell proliferation.
AB  - Pancreatic adenocarcinoma is a lethal disease because it is inoperable at the
      time of diagnosis. Therefore, the search for new therapeutic approaches is
      critical. The abnormal expression of the mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MEK) pathway and alteration in
      epigenetic modification (DNA methylation and acetylation of histones) is a common
      feature in the majority of human pancreatic adenocarcinomas. Because DNA
      methyltransferase levels are regulated by the MEK pathway, we examined the
      effects of an MEK inhibitor, PD98059, on the action of DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine (5-aza-dC), the epigenetic agent in the
      pancreatic cell line CFPAC1. Our results showed that PD98059 significantly
      potentiated the capability of 5-aza-dC to induce a cessation of cell
      proliferation concomitant with cell cycle arrest. We also observed an increase in
      tumor suppressor gene expression associated with the efficacy of treatment with
      PD98059 and 5-aza-dC. Further studies explored the molecular mechanisms by which
      5-aza-dC induced the expression of p21(WAF1). We found that 5-aza-dC induced
      acetylation of histone H3 on the p21(WAF1) gene promoter and demethylation status
      on the p21(WAF1) gene promoter region. These effects were strikingly enhanced by
      the concomitant blockade of the MEK pathway. Furthermore, knockdown of p21(WAF1)
      by small interfering RNA rescued human pancreatic cancer cells from 5-aza-dC
      mediated growth inhibition. Taken together, our results show that the MEK
      inhibitor enhanced the effects of 5-aza-dC in human pancreatic cancer cells.
      These results suggest that the MEK signal pathway may be a potential target for
      pancreatic cancer therapy. 

PMID- 24301928
TI  - Proline partially overcomes excess molybdenum toxicity in cabbage seedlings grown
      in vitro.
AB  - In vitro grown cabbage (Brassica oleracea var. capitata) seedlings exposed to
      excess molybdenum (Mo) ions exhibited severely reduced plant growth at the
      cotyledonary stage. Adding 80 mM proline (Pro) to the Mo-treated medium could
      help 50% seedlings to overcome the toxicity and grow true leaves. Under excess Mo
      stress, seedlings accumulated blue/purple anthocyanin in their cotyledons and
      hypocotyls. The anthocyanin content under Mo with 40 mM Pro was 4-fold higher
      than the control medium, MS with 40 mM Pro. The presence of Pro in the excess-Mo
      condition reduced chlorophyll a, whereas the chlorophyll b content was much
      higher than the control media of MS with and without Pro. Moreover, supplementing
      various concentrations of Pro into the Mo-stressed condition promoted the
      seedlings with higher antioxidant enzyme activities of superoxide dismutase,
      ascorbate peroxidate, and catalase. In addition, genes in the anthocyanin
      biosynthesis and accumulation pathways, phenylalanine ammonia lyase (PAL),
      chalcone synthase (CHS), flavonone 3-hydroxylase (F3H), leucoanthocyanidin
      dioxygenase (LDOX), and glutathione-S-transferase (GST), were all upregulated.
      Our study indicated that, under excess Mo stress, the antioxidant activity of
      cabbage seedlings was induced in an attempt to protect plants from the Mo-induced
      toxicity and exacerbated growth. Pro, on the other hand, functioned in producing
      higher antioxidant enzyme activity to partially help recover plant growth. 

PMID- 24301929
TI  - TaALMT1 promoter sequence compositions, acid tolerance, and Al tolerance in wheat
      cultivars and landraces from Sichuan in China.
AB  - Previous genetic studies on wheat from various sources have indicated that
      aluminum (Al) tolerance may have originated independently in USA, Brazil, and
      China. Here, TaALMT1 promoter sequences of 92 landraces and cultivars from
      Sichuan, China, were sequenced. Five promoter types (I', II, III, IV, and V) were
      observed in 39 cultivars, and only three promoter types (I, II, and III) were
      observed in 53 landraces. Among the wheat collections worldwide, only the Chinese
      Spring (CS) landrace native to Sichuan, China, carried the TaALMT1 promoter type
      III. Besides CS, two other Sichuan-bred landraces and six cultivars with TaALMT1
      promoter type III were identified in this study. In the phylogenetic tree
      constructed based on the TaALMT1 promoter sequences, type III formed a separate
      branch, which was supported by a high bootstrap value. It is likely that TaALMT1
      promoter type III originated from Sichuan-bred wheat landraces of China. In
      addition, the landraces with promoter type I showed the lowest Al tolerance among
      all landraces and cultivars. Furthermore, the cultivars with promoter type IV
      showed better Al tolerance than landraces with promoter type II. A comparison of
      acid tolerance and Al tolerance between cultivars and landraces showed that the
      landraces had better acid tolerance than the cultivars, whereas the cultivars
      showed better Al tolerance than the landraces. Moreover, significant difference
      in Al tolerance was also observed between the cultivars raised by the National
      Ministry of Agriculture and by Sichuan Province. Among the landraces from
      different regions, those from the East showed better acid tolerance and Al
      tolerance than those from the South and West of Sichuan. Additional Al-tolerant
      and acid-tolerant wheat lines were also identified. 

PMID- 24301930
TI  - Decreased expression of PIAS1 and PIAS3 in essential thrombocythemia patients.
AB  - Gain of function mutation of Janus kinase 2 (JAK2V617F) has been identified in
      Philadelphia-negative myeloproliferative diseases; about half of essential
      thrombocythemia (ET) patients harbor this mutation. The activated JAK-STAT
      pathway promotes cell proliferation, differentiation and anti-apoptosis. We
      studied the role of negative regulators of the JAK-STAT pathway, PIAS, and SOCS
      in ET patients. Twenty ET patients and 20 healthy individuals were enrolled in
      the study. Thirteen of the ET patients harbored the JAK2V617F mutation based on
      mutation analysis. Quantitative-PCR was applied to assay the expression of SOCS1,
      SOCS3, PIAS1, PIAS3. The expression levels of PIAS1 and PIAS3 were significantly
      lower in ET groups than that in normal individuals. There was no significant
      difference between JAK2V617F (+) and JAK2V617F (-) patients. SOCS1 and SOCS3
      expression did not differ between ET patients and normal individuals, or between
      JAK2V617F (+) and JAK2V617F (-) patients. We suggest that failed negative
      regulators of the JAK-STAT pathway take part in the pathomechanism of ET. 

PMID- 24301931
TI  - Identification and validation of a new grain weight QTL in rice.
AB  - The genetic control of grain weight (GW) remains poorly understood. Quantitative
      trait loci (QTLs) determining the GW of rice were identified using a natural GW
      mutant, sgw. Using a segregating population derived from sgw (low GW) and
      cultivar 9311 ('9311'; indica, high GW), the chromosome segment associated with
      GW was detected on the short arm of chromosome 7. To validate and further refine
      the locus, QTL analysis based on F2 and F3 populations was conducted, and a
      single major QTL (designated as qsgw7) affecting the 1000-grain weight of paddy
      rice was identified on the short arm region of rice chromosome 7 between simple
      sequence repeat (SSR) markers RM21997 and RM22015, where 4 bacterial artificial
      chromosome clones, OJ1339_F05, P0506F02, P0011H09, and P0519E12, were present.
      Analysis of the near isogenic line for qsgw7 (NILqsgw7) showed that the grain
      length, width, and volume of paddy rice in NILqsgw7 were significantly lower than
      those in '9311' and that the 1000-grain weight, grain length, width, volume, and
      chalkiness of brown rice in NILqsgw7 were significantly lower than those in
      '9311'. These results suggested that the qsgw7 gene, which was identified in this
      study, may be a new GW-related QTL that could affect GW and grain shape,
      especially grain plumpness. 

PMID- 24301932
TI  - Characterization and cross-species amplification of microsatellite markers in
      African Silverbill (Lonchura cantans).
AB  - We tested the cross-amplification of eight microsatellites developed for
      Bengalese finch in African Silverbill (Lonchura cantans). In order to develop
      resources for conservation genetic studies in the species L. cantans, we tested
      the amplification success and polymorphism in eight previously developed
      microsatellite loci, in L. cantans. All eight microsatellite markers were
      successfully amplified, of which all were polymorphic, with 3 to 9 alleles and an
      expected heterozygosity (HE) ranging from 0.606 to 0.718. On average, there were
      5.25 alleles/locus and a mean HE of 0.6456. These eight polymorphic markers could
      be of potential use in studies of genetic variability, population structure, and
      reproductive strategy of African Silverbills. The markers tested should be useful
      for population and conservation genetic studies in this genus, and, in
      particular, for species closely related to the source species, L. cantans. 

PMID- 24301933
TI  - Expression pattern of the zona pellucida 3 (ZP3) gene during ovarian development
      and the location of ZP3 protein in oocytes in a natural, wild triploid crucian
      carp mutant, Carassius auratus var. Pingxiangnensis.
AB  - Carassius auratus var. Pingxiangnensis (designated CaP), distributed in the
      Pingxiang region of Jiangxi Province, China, is a natural, wild triploid crucian
      carp mutant that has two reproductive development modes: gynogenesis and bisexual
      reproduction. Little information is available about the expression pattern of the
      zona pellucida 3 (ZP3) gene during ovarian development and the location of the
      ZP3 protein in oocytes of this fish. In this study, we obtained the full-length
      cDNA of ZP3 (CaP_ZP3). CaP_ZP3 contains an open reading frame of 1305 bp that
      encodes 435 amino acid residues. Real-time polymerase chain reaction (PCR) was
      used to determine the CaP_ZP3 mRNA expression levels in the ovary at different
      stages of maturation. Results revealed high levels of CaP_ZP3 expression in 4- to
      8-month-old ovaries (stage II-stage III), with a significant decline in 9- to 12
      month-old ovaries (stages IV-stage V). The high levels of CaP_ ZP3 transcripts
      during the early growth period suggest an important role for CaP_ZP3 in early
      oocyte development. In addition, a polyclonal antibody was prepared against
      CaP_ZP3, and the immunofluorescence localization was determined. CaP_ZP3 protein
      was detected close to the oocyte plasma membrane. The results also showed that no
      fluorescent signal was detected in stage I and II oocytes. CaP_ZP3 protein is
      primarily detected in stage III oocytes, and the protein accumulates as oocytes
      develop into stage IV oocytes. These results suggested that the transcription and
      translation of the CaP_ZP3 gene is asynchronous and that the transcription of the
      CaP_ZP3 protein occurs prior to its translation in this triploid fish. 

PMID- 24301934
TI  - Simple sequence repeat-based association analysis of fruit traits in eggplant
      (Solanum melongena).
AB  - Association mapping based on linkage disequilibrium (LD) provides a promising
      tool to identify quantitative trait loci (QTLs) in plant resources. A total of
      141 eggplant (Solanum melongena L.) accessions were selected to detect simple
      sequence repeat (SSR) markers associated with nine fruit traits. Population
      structure analysis was performed with 105 SSR markers, which revealed that two
      subgroups were present in this population. LD analysis exhibited an extensive
      long-range LD of approximately 11 cM. A total of 49 marker associations related
      to eight phenotypic traits were identified to involve 24 different markers,
      although no association was found with the trait of fruit glossiness. To our
      knowledge, this is the 1st approach to use a genome-wide association study in
      eggplant with SSR markers. These results suggest that the association analysis
      approach could be a useful alternative to traditional linkage mapping to detect
      putative QTLs in eggplant. 

PMID- 24301935
TI  - Sos recruitment system for the analysis of the interaction between sulfatase
      modifying factor 2 subtypes and interleukin-13.
AB  - Interleukin (IL)-13 is a central mediator in allergic asthma. Our previous
      results have indicated that sulfatase-modifying factor 2 (SUMF2) interacts with
      IL-13 and inhibits its secretion. In this study, we investigated the interactions
      between SUMF2 subtypes and 2 types of IL-13. Wild type IL-13 (wh-IL-13) and its
      mutated counterpart (mh-IL-13) were analyzed and cloned into pSos yeast
      expression vectors. Protein was expressed in host cdc25H yeast strains. A quartet
      of agar growth plates was prepared for the yeast two-hybrid system, which was
      used to detect IL-13 and SUMF2 subtype interactions. Both yeast expression
      vectors, pSos/whIL-13 and pSos/whIL-13, and recombinant expression vectors for
      the 5 subtypes of SUMF2 (pMyr/SUMF2-Vx) were constructed. Our data showed that
      all of the SUMF2 subtypes bound to whIL-13 and mhIL-13 in the CytoTrap system.
      Five SUMF2 subtypes - SUMF2-V2, SUMF2-V3, SUMF2-V4, SUMF2-V5, and SUMF2-V7-
      interacted with whIL-13 and mhIL-13. These subtypes may contribute to allergic
      asthma by mediating IL-13 release.

PMID- 24301936
TI  - A novel splicing site mutation of the GPR143 gene in a Chinese X-linked ocular
      albinism pedigree.
AB  - Ocular albinism is an X-linked inherited disease characterized by
      hypopigmentation of the iris and nystagmus. To identify a new disease-causing
      mutation of ocular albinism, we collected a Han Chinese pedigree with 7 male
      congenital nystagmus patients over 3 generations. Slit-lamp photography and
      optical coherence tomography were performed for the proband. Genomic DNA was
      extracted from a whole blood sample from the proband using the high-salt method.
      Polymerase chain reaction (PCR) sequencing was carried out for GPR143 and FRMD7
      genes. The three-dimensional structures of the wild-type and mutant GPR143
      proteins were determined using SWISS-MODEL. The transmission of the disease in
      the pedigree clearly followed an X-linked pattern. The proband had significant
      iris and fundus hypopigmentation. Optical coherence tomography showed severe
      foveal hypoplasias in both eyes of the proband. A novel splicing site (G/C)
      mutation was found on the boundary of the 6th intron and the 7th exon of the
      GPR143 gene, resulting in a 9-amino-acid deletion (codons 257-265) in the 6th
      transmembrane domain of the GPR143 protein. In conclusion, a novel splicing site
      mutation of the GPR143 gene was found in a Han Chinese congenital ocular albinism
      pedigree. 

PMID- 24301937
TI  - Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast
      cancer in Mexican women.
AB  - The tumor necrosis factor-alpha (TNF-alpha) gene plays an important role in cell
      proliferation, differentiation, apoptosis, lipid metabolism, coagulation, insulin
      resistance, and endothelial function. Polymorphisms of TNF-alpha have been
      associated with cancer. We examined the role of the -308G>A polymorphism in this
      gene by comparing the genotypes of 294 healthy Mexican women with those of 465
      Mexican women with breast cancer. The observed genotype frequencies for controls
      and breast cancer patients were 1 and 14% for AA, 13 and 21% for GA, and 86 and
      65% for GG, respectively. We found that the odds ratio (OR) for AA genotype was
      2.4, with a 95% confidence interval (95%CI) of 5.9-101.1 (P = 0.0001). The
      association was also evident when comparing the distribution of the AA-GA
      genotype in patients in the following categories: 1) premenopause and obesity I
      (OR = 3.5, 95%CI = 1.3-9.3, P = 0.008), 2) Her-2 neu and tumor stage I-II (OR =
      2.5, 95%CI = 1.31-4.8, P = 0.004), 3) premenopause and tumor stage III-IV (OR =
      1.7, 95%CI = 1.0-2.9, P = 0.034), 4) chemotherapy non-response and abnormal
      hematocrit (OR = 2.4, 95%CI = 1.2-4.8, P = 0.015), 5) body mass index and Her-2
      neu and III-IV tumor stage (OR = 2.8, 95%CI = 1.2- 6.6, P = 0.016), and 6) nodule
      metastasis and K-I67 (OR = 4.0, 95%CI = 1.01-15.7, P = 0.038). We concluded that
      the genotypes AA-GA of the -308G>A polymorphism in TNF-alpha significantly
      contribute to breast cancer susceptibility in the analyzed sample from the
      Mexican population. 

PMID- 24301938
TI  - Genetic diversity analysis of oriental river prawn, Macrobrachium nipponense, in
      Yellow River using microsatellite marker.
AB  - To assess the genetic status of this species, the genetic diversity of wild
      Macrobrachium nipponense from seven geographic locations in the Yellow River
      basin were investigated using 20 polymorphic microsatellite DNA loci. The genetic
      diversity between populations was indicated by the mean number of alleles per
      locus and mean observed heterozygosity (H) and the expected H, which was arranged
      from 2 to 10, from 0.4705 to 0.5731, and from 0.5174 to 0.6146, respectively.
      Hardy-Weinberg equilibrium analysis indicated that a deficiency of heterozygotes
      existed in all seven populations. Both the F(ST) and AMOVA analyses showed that
      there is significant difference on population differentiation among populations.
      The UPGMA clustering tree demonstrated that their close relationship is
      consistent with their geographic proximity. The data suggest that this Yellow
      River population has a wide genetic base that is suitable for breeding.

PMID- 24301939
TI  - Genetic diversity and relationships among accessions of five crested wheatgrass
      species (Poaceae: Agropyron) based on gliadin analysis.
AB  - Agropyron Gaertn. is the most important genus in Triticeae (Poaceae), which
      includes many forage grasses with high economic value. The genetic diversity and
      relationships of 36 accessions from five crested wheatgrass species were analyzed
      by gliadin markers. A total of 54 product bands were detected after acid
      polyacrylamide gel electrophoresis (A-PAGE), of which 100% were polymorphic. The
      genetic similarity coefficient based on Nei-Li's method ranged from 0.065 to
      0.755 with an average of 0.451. The Shannon diversity information index showed
      that there was a high level of genetic diversity among the accessions. An
      unweighted pair group method with arithmetic average (UPGMA) dendrogram was
      constructed based on the Nei-Li's genetic similarity coefficients, which showed
      the phylogenetic relationships among accessions of different species. Analysis of
      molecular variance (AMOVA) showed that the proportion of variance explained by
      inter- and intraspecific variance was 9.34 and 90.66%, respectively, which
      revealed that the genetic variations within species were higher than the
      variations among species. Based on pairwise genetic distances (PhiST) among
      species, the cluster analysis indicated that A. mongolicum had a low-affinity
      relationship with other species, while A. fragile showed a close relationship
      with A. cristatum ssp pectinatum. Finally, the implications of the results for
      the taxonomy of Agropyron were discussed. 

PMID- 24301940
TI  - Effects of genetic variants of CCR5 chemokine receptors on oral squamous cell
      carcinoma.
AB  - We aimed to evaluate the effect of genetic variants of the chemokine C-C motif
      receptor (CCR5) in the pathogenesis of oral squamous cell carcinoma (OSCC). A
      total of 127 patients diagnosed with OSCC and 104 healthy individuals were
      included in the study. The polymorphisms CCR5 59029 and CCR5-delta32 were
      assessed with the polymerase chain reaction-restricted fragment length
      polymorphism (PCR-RFLP) method from peripheral blood samples of both groups.
      There was a statistically significant difference between the control and patient
      groups for CCR5 59029 A/G genotypes (P < 0.01). Individuals carrying the CCR5
      59029 G allele (GG +AG genotypes) had a 2.84-fold increased risk for OSCC (P <
      0.0001), and the CCR5 59029 AA genotype frequency was higher in the control group
      than in the patient group (P < 0.0001). The CCR5-delta 32 genotype frequencies
      did not differ significantly between controls and cases (P > 0.05). CCR5 59029 GG
      and CCR5-delta32 DD + ID genotype frequencies were significantly increased in
      Grade II-III OSCC patients compared with Grade I-II OSCC patients. In conclusion,
      these results suggested that the G allele of the CCR5 59029 polymorphism might be
      a risk factor due to the loss of receptor function that might cause increased
      inflammation leading to the development of OSCC. 

PMID- 24301941
TI  - RAPD and barcode analyses of groupers of the genus Epinephelus.
AB  - The diversity of Epinephelus species was investigated throughout Thailand. Random
      amplified polymorphic DNA successfully produced 1300 bands that were
      phylogenetically informative and used to construct cladograms. Values of pairwise
      genetic similarity (S) within species ranged from 0.65 in E. erythrurus to 0.99
      in E. malabaricus. The interspecific values of S ranged from 0.23 between E.
      malabaricus and E. bleekeri to 0.66 between E. coeruleopunctatus and E.
      erythrurus. The intraspecific nucleotide variation ranged from 0.037 to 0.159 in
      the mitochondrially encoded 16S RNA (MT-RNR2) region and from 0.003 to 0.157 for
      the mitochondrially encoded cytochrome c oxidase I (MT-CO1) region. All sequences
      were submitted individually to GenBank. The barcode sequences of Thai species of
      Epinephelus were aligned to the same species found in GenBank. For the MT-RNR2
      gene region, intraspecific nucleotide variation ranged from 0.000 to 0.121, and
      interspecific nucleotide variation ranged from 0.003 to 0.146. For the MT-CO1
      gene region, intraspecific nucleotide variation ranged from 0.000 to 0.140, and
      interspecific nucleotide variation ranged from 0.000 to 0.166. The MT-RNR2 data
      indicate that some species, including E. bleekeri from India and E. malabaricus
      from Thailand are not monophyletic. Additionally, the MT-CO1 data indicated that
      E. bleekeri, E. quoyanus and E. coeruleopunctatus are not monophyletic. The
      sequences of E. lanceolatus from each country are highly conserved, with genetic
      distances ranging from 0.000 to 0.003. Another important result from this study
      is that the barcode sequence from Thai E. erythrurus was previously not present
      in the GenBank. 

PMID- 24301942
TI  - Changes of Th1/Th2 cytokines in immunocompetent patients with pulmonary
      cryptococcosis.
AB  - The aim of this study was to investigate the changes of Th1/Th2 cytokines in
      immunocompetent patients with pulmonary cryptococcosis (PC). Twenty
      immunocompetent patients with PC were identified by histopathological examination
      and were enrolled in the study along with the age- and gender-matched healthy
      controls. The serum concentrations of interferon-gamma (IFN-gamma), interleukin-4
      (IL-4), and interleukin-12 (IL-12) were measured by enzyme-linked immunosorbent
      assay (ELISA). Peripheral blood mononuclear cells (PBMCs) in both groups were
      isolated and incubated with or without recombinant human IL-12 (rhIL-12) for 48
      h, and the concentrations of IFN-g and IL-4 in the supernatant were measured by
      ELISA. Serum IFN-gamma levels were greatly decreased in the patients compared
      with control groups (P < 0.01), whereas no significant difference was observed in
      serum IL-4 and IL-12 levels. The concentrations of IFN-gamma and IL-4 in the
      supernatant of PBMCs without the stimulation of rhIL-12 showed no differences
      between the two groups. Treatment with rhIL-12 stimulated the release of IFN
      gamma, but not IL-4, into the supernatant of PBMCs in both groups, with a lower
      increase observed in the patients (4.3-fold) compared to that of controls (7.9
      fold) (P < 0.01). Serum IFN-gamma levels may be dampened in immunocompetent
      patients with PC with no significant changes in serum IL-4 and IL-12 levels. The
      deficiency in the response to IL-12 stimulation of Th1 cells may be one of the
      underlying mechanisms for the decline in serum IFN-gamma levels. 

PMID- 24301943
TI  - Phylogenetic analysis of substrate-binding subunits in an osmoprotectant system.
AB  - Substrate-binding subunits are important components of the solute importation
      system, known as the osmoprotectant system, which consists of a membrane protein
      belonging to the ABC superfamily. These molecules recognize specific substrates
      that have different physiological roles in prokaryotes, i.e., roles that
      contribute to the survival of these organisms in environments with high
      concentrations of salt. Using the MEGA software, this study performed a
      phylogenetic analysis of 431 nucleotide sequences of these subunits, orthologous
      to each other, collected from the http://www.genome.jp/kegg/ database. This
      analysis allowed phylogenetic trees to be generated, clearly demonstrating that
      there was horizontal transfer of some genes through sharing by different
      organisms. Furthermore, two probable ancestral sequences were generated that
      showed homology with permeases that transport choline, glycine betaine, and
      carnitine, which are trimethylamines currently present in various prokaryotes.
      Therefore, this system probably arose in prokaryotic organisms with the basic
      function of capturing nutrients, and by performing this basal function and being
      shared with other organisms, it was fixed in the genome. However, because of
      prokaryote habitat diversification, this system contributed decisively to the
      adaptation of these organisms to different environments, especially environments
      that had a high salt concentration, thus acting as an osmoprotection system,
      which is how they are currently categorized. 

PMID- 24301944
TI  - In-depth pedigree analysis in a large Brazilian Nellore herd.
AB  - A large herd of Nellore cattle was evaluated using in-depth pedigree analyses.
      Taking into account the incomplete pedigree due to the use of multiple young
      sires for mating, the average inbreeding coefficient was calculated as 1.73% for
      the last generation, which was higher than the regular inbreeding coefficient
      (0.25%). The effective population size was estimated to be 114, 245, and 101 for
      the time periods 1995-1999, 1999-2003, and 2003-2007, respectively. Parameters
      based on the probability of gene origin were used to describe the genetic
      diversity over time in the herd. The effective number of founders, ancestors, and
      founder genomes decreased over time, showing an overall loss of genetic
      diversity. In the last five-year period (2003-2007), based on available pedigree
      information, one prominent ancestor contributed 10.6% to the gene pool of the
      herd, and 30% of this pool was contributed by 31 ancestors. The analysis of
      inbreeding under random mating indicated that the mating strategies used in the
      herd are slowing down inbreeding rates. However, it is advisable to continue
      monitoring the inbreeding rates and genetic diversity in this herd in the future.

PMID- 24301945
TI  - New insights into the prolactin-RsaI (PRL-RsaI) locus in Chinese Holstein cows
      and its effect on milk performance traits.
AB  - Prolactin (PRL) plays central roles in mammals' reproduction, gland development,
      milk secretion, and the expression of milk protein genes. In dairy cattle, the
      PRL gene is a potential quantitative trait locus and genetic marker related to
      milk performance traits. Here, a total of 586 randomly selected Chinese Holstein
      cows were genotyped for locus PRL-RsaI. One haplotype block containing eight SNPs
      was identified in the region from intron 3 to intron 4 of the PRL gene in Chinese
      Holstein cows. One tag SNP (7545 G -> A) was selected to represent the haplotype
      block defined by the genotypic data. The cows with genotype AA of this tag SNP
      had a higher milk yield at 305 days (8457 +/- 938 kg) than the cows with GA (7537
      +/- 1278 kg; P < 0.01) or GG (7757 +/- 1174 kg; P < 0.05). This suggests that the
      haplotype block examined in this study contains important markers for milk
      production traits in Chinese Holstein cows.

PMID- 24301946
TI  - Physical properties of gastrointestinal stromal tumors based on atomic force
      microscope analysis.
AB  - This study was designed to detect the stiffness of single living gastrointestinal
      stromal tumor (GIST) cells in vitro using an atomic force microscope as a probe
      tool. We determined that the stiffness of living GIST cells was 3913 Pa, the
      stiffness of the membrane was 642 Pa, and the stiffness of the cytoplasm was
      17,550 Pa. For comparison, we also determined the stiffness of a normal stomach
      cell, which was 7374 Pa, and that of in vitro GIST cells after 2 h of exposure,
      which was 10,680 Pa. Measuring the mechanical properties of individual GIST cells
      might provide more complementary information for the diagnosis and treatment of
      GISTs from the perspective of physical characteristics. 

PMID- 24301947
TI  - Deposition rule of yolk cholesterol in two different breeds of laying hens.
AB  - The objective of this study was to investigate the deposition rule of yolk
      cholesterol in Lushi Green-shelled and Silky Fowl layers. A total of 90 layers of
      each breed were selected at an age of 15 to 51 weeks. Productive performance was
      recorded on a weekly basis, whereas yolk cholesterol was determined at 4-week
      intervals from 21 to 51 weeks of age. The average yolk cholesterol content of
      Silky Fowl layers during the laying period was higher than that of Lushi Green
      shelled layers (58.16 and 49.67%, P > 0.05). Yolk cholesterol content decreased
      at 21 to 31 weeks of the laying period, whereas a non-significant increasing
      trend was observed during 31 to 51 weeks of laying period. In conclusion, yolk
      cholesterol content is not only dependent on the age of hen but also the breed of
      layers. 

PMID- 24301948
TI  - Further evidence for the contribution of the BRCA1-interacting protein-terminal
      helicase 1 (BRIP1) gene in breast cancer susceptibility.
AB  - BRCA1-interacting protein C-terminal helicase 1 (BRIP1) is a DNA helicase that
      influences the DNA repair ability and tumor suppressor function of BRCA1.
      Truncating BRIP1 mutations have been described as cancer susceptibility alleles.
      To evaluate BRIP1 polymorphisms as risk factors for breast cancer, we performed a
      detailed analysis of possible single nucleotide polymorphisms (rs2048718,
      rs4988344, rs8077088, rs6504074, rs4986764, rs4986763, rs11079454, rs7213430,
      rs34289250, rs4988345, and rs12937080) using the MassARRAY system. A total of 319
      patients with breast cancer and 306 healthy control females from the Chinese Han
      population enrolled in the study. A weak association was found between the
      rs4986764 allele (exon 18) and breast cancer. The frequency of the rs4986764 C
      allele was significantly higher in breast cancer patients than in healthy
      controls [chi(2) = 4.089, P = 0.043, odds ratio (OR) = 0.781, 95% confidence
      interval (CI) = 0.614-0.992]. Additionally, our study is the first to identify a
      significant association between rs7213430 and breast cancer. Compared to healthy
      controls, patients with breast cancer had a higher frequency of the rs7213430 A
      allele (chi(2) = 8.865, P = 0.003, OR = 0.700, 95%CI = 0.553-0.886). Furthermore,
      linkage disequilibrium was observed in two blocks (D' > 0.9). While significantly
      more T-A-C haplotypes (P = 0.001, block 1) were found in breast cancer patients,
      the frequency of T-T haplotypes (P = 0.008, block 2) was significantly higher in
      healthy controls. The possible association among rs4986764, rs7213430, and breast
      cancer risk merits further validation in an independent case-control study. 

PMID- 24301949
TI  - Polymorphism of SREBP1 is associated with beef fatty acid composition in
      Simmental bulls.
AB  - The sterol regulatory element binding factor 1 gene (SREBP1) plays an important
      role in the biosynthesis of fatty acids and cholesterol, and in lipid metabolism.
      The objective of this study was to investigate the effect of genetic
      polymorphisms of SREBP1 on the fatty acid composition of muscle and carcass
      traits in Simmental bulls and Snow Dragon black cattle. The 84-bp
      insertion/deletion (indel) in intron 5 of the bovine SREBP1 gene was genotyped by
      polymerase chain reaction to investigate its associations with traits. The
      results showed that the 84-bp indel in intron 5 was significantly associated with
      palmitoleic acid (C16:1), stearic acid (C18:0), saturated fatty acids (SFA),
      triglycerides (TAG), and the C16 index in Simmental bulls (P < 0.05). Cattle with
      the LL genotype had higher palmitic acid (C16:1), triglycerides, and C16 index
      but lower stearic acid (C18:0) and SFA compared to those with the LS genotype (P
      < 0.05). In conclusion, the 84-bp indel of SREBP1 could be used as a genetic
      marker for selecting Simmental breeding stock for healthier fatty acid
      composition. 

PMID- 24301950
TI  - Entoepidemiology of Chagas disease in northwest Sao Paulo and cytogenetic
      analysis of its main vector, Triatoma sordida (Hemiptera: Triatominae).
AB  - One century after the discovery of Chagas disease, it is still considered as a
      major health problem, causing more deaths in the Americas than any other
      parasitic disease. The northwest region of Sao Paulo, a macro-region that
      includes cities with a high-quality of life, has particularly high rates of
      Chagas disease. Therefore, this study aimed to assess the number of patients with
      Chagas disease, and to identify the triatomine fauna in the northwest region of
      Sao Paulo State, and to cytogenetically analyze Triatoma sordida mutants, thus
      providing new knowledge to control these species and avoid possible infections by
      Chagas disease. A total of 700 Chagas patients of both genders and variable age,
      who were born in and residents of the northwest region of the State of Sao Paulo
      were recruited for this study. Regarding the entoepidemiological fauna, both T.
      sordida and Rhodnius neglectus were captured from 2004 to 2011 in the northwest
      region of the Sao Paulo; however, T. sordida was the predominant species. Some of
      these collected triatomines were infected by Trypanosoma cruzi in several
      developmental stages. Furthermore, the lactoacetic orcein method was used for
      cytogenetic analysis. Several abnormalities were observed during meiosis of the
      T. sordida mutants, including condensed chromosomes with no chiasma, chromatin
      bridges between the autosomes, and some non-pairing homologous chromosomes. Thus,
      our study suggests that Chagas disease is currently not under control in Brazil.
      Furthermore, we suggest that cryptic speciation may be occurring in populations
      of T. sordida of Brazil. Further studies are necessary to understand the
      mechanisms behind these phenomena. 

PMID- 24301951
TI  - Cloning and characterization of major histocompatibility complex class II genes
      in the stone flounder Kareius bicoloratus (Pleuronectidae).
AB  - Major histocompatibility complex (MHC) class II genes play important recognition
      roles in the immune system in vertebrates. We cloned the MHC class II genes A and
      B in the stone flounder (Kareius bicoloratus). The full-length cDNA and DNA
      sequences of both genes were obtained, and their characteristic motifs were
      analyzed. The DNA sequence of stone flounder MHC class II A consists of four
      exons, while gene B contains six exons. The extra intron in gene B might be a
      common feature in most of its Acanthopterygii orthologs. Several conserved motifs
      were identified by multiple deduced amino acid sequence alignments of the two
      genes and their orthologs. The peptide sequences of alpha chain and beta chain
      shared identity of 86.0-30.1% and 69.8-31.3% with their orthologs, respectively.
      Bayes phylogenetic trees showed that the stone flounder is closely related to the
      spotted halibut (Verasper variegates), and the half-smooth tongue sole
      (Cynoglossus semilaevis). Real-time quantitative PCR showed that in the stone
      flounder, both genes A and B are highly or moderately expressed in several
      tissues, including the intestine, spleen and gills, and less expressed or
      undetectable in the liver, kidney, brain, heart, and gonads. These expression
      patterns differed slightly from those in other teleosts. This might be a unique
      phenomenon in the stone flounder. This first study of MHC genes in stone flounder
      could provide reference data for comparative studies. 

PMID- 24301952
TI  - Evaluation of genetic diversity in Pampus argenteus using SSR markers.
AB  - In order to evaluate the germplasm resources of Pampus argenteus silver pomfret,
      the genetic diversity and population structure of 132 silver pomfret samples
      collected from the three regions (the East China Sea, the Yellow Sea and the
      Bohai Sea) were examined using 13 polymorphic microsatellite loci. Results
      indicated a high level of genetic diversity. The total number of observed alleles
      was 68, the mean allele number was 5.46 per locus, and the mean number of
      effective alleles was 4.91. The polymorphism information content ranged from 0.58
      to 0.88. For the 13 polymorphic microsatellite loci, the results of analysis of
      molecular variance indicated that 92.45% of the genetic variation was contained
      within populations. Unweighted pair group method with arithmetic mean cluster
      analysis revealed significant genealogical branches or clusters corresponding to
      sampling localities. We concluded that there was high genetic diversity in these
      silver pomfret populations, and that this diversity was related to the complex
      environment. These results would contribute to important knowledge of genetic
      diversity and population structure, which would be crucial for establishing
      appropriate fishery management stocks for this species. 

PMID- 24301953
TI  - Expression of multidrug resistance 1 and multidrug resistance-related protein 1
      in C57BL/6 mice treated with benzene.
AB  - ATP-binding cassette super family (ABC) proteins are considered key to oncology
      and pharmacology studies. We examined the effect of benzene on ABC pump protein
      levels in C57BL/6 mouse bone marrow mononuclear cells. After a 2-week gavage (200
      mg/kg, 5 days per week), the number of peripheral leukocytes, lymphocytes and
      basophils dropped significantly; there was also a significant decrease in MDR1
      and MRP1 gene expression. A significant reduction in expression of P-gp was
      found; however, there was no significant decrease in the expression of MRP1 and
      NF-kappaB p65. We conclude that regulation of membrane efflux transport protein
      could be a factor in benzene hematotoxicity. 

PMID- 24301954
TI  - Transient increase in IL-1beta, IL-6 and TNF-alpha gene expression in rat liver
      exposed to gold nanoparticles.
AB  - Most studies have used in vitro systems to test inflammatory responses of
      nanoparticles; these may not reflect the real biological response of body organs.
      In fact, certain nanoparticles have provoked opposite effects under in vitro and
      in vivo conditions. Current understanding of the biocompatibility of gold
      nanoparticles is controversial. We studied the acute (1 day) and sub-chronic (5
      days) effects of gold nanoparticles (10 and 50 nm in diameter) on expression of
      interleukin-1 beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha)
      in rat liver. Real-time PCR analysis showed that gold nanoparticles of both sizes
      significantly increased cytokine gene expression on day 1; this had subsided by
      day 5. The 50-nm gold nanoparticle produced more severe inflammation than the
      smaller gold nanoparticle. These findings indicate a possible biocompatibility of
      medium-sized gold nanoparticles, as they caused only a transient increase in
      proinflammatory cytokines, followed by normalization during sub-chronic repeated
      exposure. 

PMID- 24301955
TI  - Case report: A novel TET2 mutation in a patient with refractory cytopenia with
      multilineage dysplasia.
AB  - Myelodysplastic syndrome diagnosis of karyotypically normal patients may be
      elusive because it relies exclusively on morphological and clinical data. In
      routine practice, finding of an acquired mutation or a cytogenetic abnormality
      provides irrefutable evidence of the clonal nature of that disease. Recurrent
      deletions and somatic mutations in TET2, a gene involved in epigenetic
      regulation, have been reported in about 20% of adult patients with
      myelodysplastic syndrome. We report a novel g.95805C>T, nonsense TET2 mutation,
      leading to a premature stop codon (p.Gln913*), in an adult patient with
      refractory cytopenia with multilineage dysplasia. 

PMID- 24301956
TI  - Tumor-associated fibroblast-conditioned medium promotes tumor cell proliferation
      and angiogenesis.
AB  - This study aimed to explore how tumor-associated fibroblasts (TAFs) promote the
      proliferation and angiogenesis of tumor cells via the paracrine mechanism in
      vitro. Conditioned media (CM) of ovarian TAFs and normal fibroblasts (NFs) were
      collected. Ovarian cancer cells (OCCs) were treated with 2 mL TAFs-CM and NFs-CM
      in experimental and control groups, respectively; 20 mM SB431512, a specific
      small molecule inhibitor of transforming growth factor-beta (TGF-beta), was added
      in the experimental group as the intervention group. The cell cycle was
      determined in each group. mRNA expressions of proliferating cell nuclear antigen
      (PCNA), alpha-smooth muscle actin (alpha-SMA), and vascular endothelial growth
      factor (VEGF), and protein expressions of alpha-SMA and VEGF were detected in
      each group. Proliferation of OCCs was significantly promoted in the experimental
      group compared with that of the control group. The proliferative effect was
      obviously inhibited in the intervention group. The mRNA expressions of PCNA,
      alpha-SMA, and VEGF, and protein expressions of alpha-SMA and VEGF were all
      dramatically up-regulated in each group, and were strongly inhibited by SB
      431512. TAFs promote the proliferation of OCCs via paracrine and up-regulated
      expression of angiogenic genes and proteins, which can be effectively inhibited
      by inhibiting the TGF-beta signaling pathway. 

PMID- 24301957
TI  - Cloning, characterization, and expression of the macrophage migration inhibitory
      factor gene from the Pacific white shrimp Litopenaeus vannamei (Penaeidae).
AB  - The macrophage migration inhibitory factor (MIF) is an important proinflammatory
      cytokine that mediates both innate and adaptive immune responses. In this study,
      we identified a homolog of MIF in the Pacific white shrimp Litopenaeus vannamei.
      The MIF cDNA contained a 363-bp open reading frame encoding a 120-amino acid
      protein with a calculated molecular mass of 13.442 kDa and a theoretical
      isoelectric point of 6.57. The L. vannamei MIF shared high amino acid identity
      with MIFs of other invertebrates. Tissue distribution analysis by quantitative
      real-time polymerase chain reaction (qRT-PCR) revealed that the L. vannamei MIF
      was abundantly expressed in the blood, heart, and hepatopancreas, was moderately
      expressed in the gill, and was weakly expressed in the muscle and intestine.
      Furthermore, in order to gain a basic understanding of the role of MIF in the
      shrimp immune response against viral infection, its mRNA expression was
      determined in the hepatopancreas of L. vannamei at different stages after white
      spot syndrome virus (WSSV) challenge using qRT-PCR. The result indicated that the
      expression of MIF was significantly upregulated after WSSV injection, suggesting
      that MIF may be involved in the response to viral infection in shrimp. 

PMID- 24301958
TI  - Characterization of Anatolian traditional quince cultivars, based on
      microsatellite markers.
AB  - We conducted simple sequence repeat (SSR) analyses of 15 traditional quince
      (Cydonia oblonga) cultivars from Anatolian gene sources for molecular
      characterization and investigation of genetic relationships. Three pear and two
      apple cultivars were used as references for SSR locus data analysis and to
      determine allele profiles between species. Eight SSR loci that were developed
      from apple and pear were used, and a total of 44 alleles were found among quince
      cultivars. The CH01F02 locus was found to have the highest identification
      probability, while the CH04E03 locus had the lowest identification probability.
      Analysis of similarity ratios between quince cultivars showed that the lowest
      similarity ratio was 18% (Esme-Bardacik +/- k), while the highest similarity
      ratio was 87% (Bursa-Osmancik +/- k and Osmancik +/- k-Viranyadevi). In the
      phylogenetic dendrogram, Esme quince showed separate branching from other quince
      cultivars, and no synonymous accessions were found. These results suggest that
      SSR markers from pear and apple could be used to determine genetic variation
      among quince cultivars. These findings can be used to guide future quince
      breeding and management studies.

PMID- 24301959
TI  - Influence of animals obtained using embryo transfer on the genetic evaluation of
      growth in Simmental beef cattle with random regression models.
AB  - Weight records of Simmental beef cattle were used in a genetic evaluation of
      growth with and without embryo transfer (ET). A random regression model in which
      ET individuals were excluded (RRM1) contained 29,510 records from 10,659 animals,
      while another model that did not exclude these animals (RRM2) contained 62,895
      records from 23,160 animals. The fixed and random regressions were represented by
      continuous functions, and a model with an order of three for the fixed curve and
      random effects was used to consider the homogeneity of residual variance. In
      general, the (co)variance components were similar in both models, except the
      maternal permanent environment and residual components. The direct heritability
      in RRM1 and RRM2 showed the same behavior with oscillations along the growth
      curve and were slightly higher in RRM1. Generally, the estimated correlations
      were the same and smaller as the ages distanced themselves. The inclusion of
      animals from ET in genetic evaluations can be done using random regression
      models; the inclusion of these animals would provide potential accuracy gains and
      greater genetic gains per unit time because of the reduction in the generation
      interval from the use of this reproductive technique. 

PMID- 24301960
TI  - Development and characterization of novel expressed sequence tag-derived simple
      sequence repeat markers in Hevea brasiliensis (rubber tree).
AB  - Cultivated clones of Hevea brasiliensis have a narrow genetic base. In order to
      broaden the genetic base, it is first necessary to investigate the genetic
      diversity of wild populations. Expressed sequence tag-simple sequence repeat (EST
      SSR) markers were developed to investigate the genetic diversity of Hevea
      populations. Four hundred and thirty microsatellites were identified and 148
      primers were designed to amplify the loci. Twenty-nine primer pairs were
      synthesized and evaluated for their ability to detect genetic polymorphisms among
      40 wild accessions of H. brasiliensis. Twenty-one of the 29 loci were
      polymorphic. The number of alleles per locus in the 40 accessions ranged from 2
      to 7. H(O) and H(E) at each locus ranged from 0.0000 to 0.9000 and from 0.0000 to
      0.8704, respectively. All 21 loci could amplify in H. brasiliensis, H.
      pauciflora, H. nitida, H. spruceana, and H. camargoana. The EST-SSR primers
      developed herein can be used in genetic diversity and structure studies in H.
      brasiliensis.

PMID- 24301961
TI  - Isolation and characterization of polymorphic microsatellite loci in the swimming
      crab Portunus trituberculatus (Portunidae).
AB  - The Swimming crab Portunus trituberculatus (Portunidae) is an important
      economically food species. To provide molecular markers for P. trituberculatus,
      we isolated and characterized polymorphic microsatellite markers. We developed a
      5'-anchored genomic library of P. trituberculatus DNA, and derived 45 positive
      clones. We designed 30 pairs of primers from the sequences of these clones, and
      10 of which were polymorphic. The loci were screened in 31 P. trituberculatus
      individuals; the number of alleles ranged from 2 to 5. The observed
      heterozygosity ranged from 0.20 to 0.49 and the expected heterozygosity ranged
      from 0.50 to 0.78. The polymorphism information content per locus ranged from
      0.37 to 0.75. These polymorphic microsatellite markers may provide some useful
      information for the population genetic studies of swimming crab and other
      Portunus species. 

PMID- 24301962
TI  - Porous coordination polymers based on functionalized Schiff base linkers:
      enhanced CO2 uptake by pore surface modification.
AB  - We report the synthesis, structural characterization and adsorption properties of
      three new porous coordination polymers {[Cu(Meazpy)0.5(glut)](H2O)}n (2),
      {[Zn(azpy)0.5(terep)](H2O)}n (3), and {[Zn(Meazpy)0.5(terep)]}n (4) [glut =
      glutarate, terep = terephthalate, azpy = N,N'-bis-(pyridin-4
      ylmethylene)hydrazine and Meazpy = N,N'-bis-(1-pyridin-4-ylethylidene)hydrazine]
      composed of mixed linkers systems. Structure determination reveals that all three
      compounds have three-dimensional (3D) coordination frameworks bridged by
      dicarboxylates and Schiff base linkers. In all cases 2D dicarboxylate layers are
      supported by paddle-wheel M2(CO2)4 SBUs extended in three dimensions by designed
      Schiff base linkers. Compound 1, which has been reported in a paper earlier by
      our group, is a robust porous three-dimensional (3D) framework whose pore surface
      was found to be decorated with the -CH=N- groups of a linear Schiff base (azpy)
      and it showed reversible single-crystal-to-single-crystal transformation and
      selective CO2 uptake. By using another linear Schiff base linker Meazpy, we have
      synthesized compound 2 which is isostructural with 1, having an additional methyl
      group pointing towards the pore. Like 1 it also shows a reversible single-crystal
      to-single-crystal transformation upon dehydration and rehydration. The dehydrated
      framework of 2 exhibits 50% enhanced CO2 uptake compared to 1. This has been
      achieved by the pore surface modification effected upon changing the pillar
      backbone from a -CH=N- to -CMe=N- group. It also adsorbs water vapour at 298 K.
      In the case of the two isostructural 3D MOFs 3and 4, the use of a rigid
      carboxylate (terephthalate) linker arrested porosity by three-fold
      interpenetration. We showed that the use of aliphatic dicarboxylate (glutarate)
      results in a non-interpenetrated framework rather than the common interpenetrated
      framework with aromatic dicarboxylates in mixed ligand systems.

PMID- 24301963
TI  - Design and synthesis of N-aryl isothioureas as a novel class of gastric H(+)
      /K(+) -ATPase inhibitors.
AB  - To find new H(+) /K(+) -ATPase inhibitors for the treatment of peptic ulcer
      disease, a series of novel N-aryl isothiourea derivatives were synthesized and
      their structures were identified by (1) H NMR and GC-MS. The effects of these
      compounds on inhibiting gastric acid secretion were evaluated by the guinea pig
      stomach mucous membrane study with pantoprazole magnesium as a positive control.
      The results showed that, of the 37 N-aryl isothiourea compounds synthesized, 20
      compounds have comparable or stronger gastric acid inhibitory activities than
      that of pantoprazole magnesium. The quantitative structure-activity relationships
      (QSARs) of the N-aryl isothiourea compounds were also studied by comparative
      molecular field analysis (CoMFA) computation, and the model structure that was
      supposed to give more powerful bioactivities was finally predicted. 

PMID- 24301964
TI  - Synthesis and evaluation of antioxidant properties of novel 1,2,4-triazole-based
      schiff base heterocycles.
AB  - A series of 1,2,4-triazole-based Schiff base heterocyclic compounds (5a-f and 8a
      i) and phenethylamines (7a-h) were synthesized and evaluated for antioxidant
      properties by free-radical scavenging, anti-hemolytic activity, lipid
      peroxidation, and their protective effects against DNA oxidative damage.
      Compounds 7c, 7d, 7h, 8b, and 8i showed promising DPPH(*) radical scavenging
      activity with the level of inhibition between 86.8% and 94%. Compounds 8a, 8b,
      8d, 8g, and 8i were effective against the oxidative hemolysis of human
      erythrocytes and lipid peroxidation, in a dose-dependent manner, with IC50 values
      in the range of 55.7-80.7 and 53.2-81.2 ug/mL, respectively. Compounds 8a and 8b
      were effective against oxidative damage on erythrocyte ghost membrane proteins,
      and 8g and 8i were able to protect against DNA oxidative damage. 

PMID- 24301968
TI  - Electrolyte system strategies for anionic ITP with ESI-MS detection. 3. The ITP
      spacer technique in moving-boundary systems and configurations with two self
      maintained ITP subsystems.
AB  - This contribution is the third part of the project on strategies used in the
      selection and tuning of electrolyte systems for anionic ITP with ESI-MS
      detection. The strategy presented here is based on the creation of self
      maintained ITP subsystems in moving-boundary systems and describes two new
      principal approaches offering physical separation of analyte zones from their
      common ITP stack and/or simultaneous selective stacking of two different analyte
      groups. Both strategic directions are based on extending the number of components
      forming the electrolyte system by adding a third suitable anion. The first method
      is the application of the spacer technique to moving-boundary anionic ITP
      systems, the second method is a technique utilizing a moving-boundary ITP system
      in which two ITP subsystems exist and move with mutually different velocities. It
      is essential for ESI detection that both methods can be based on electrolyte
      systems containing only several simple chemicals, such as simple volatile organic
      acids (formic and acetic) and their ammonium salts. The properties of both
      techniques are defined theoretically and discussed from the viewpoint of their
      applicability to trace analysis by ITP-ESI-MS. Examples of system design for
      selected model separations of preservatives and pharmaceuticals illustrate the
      validity of the theoretical model and application potential of the proposed
      techniques by both computer simulations and experiments. Both new methods enhance
      the application range of ITP-MS and may be beneficial particularly for complex
      multicomponent samples or for analytes with identical molecular mass. 

PMID- 24301969
TI  - Genetic control of chlorophyll biosynthesis by the plastome in some Oenothera
      species (subgenus Munzia).
AB  - Reciprocal differences in the rates of chlorophyll (Chl) formation during early
      stages of greening are observed in hybrid seedlings with identical genomes
      derived from reciprocal crosses between Oenothera berteriana (=villaricae) and
      Oe. odorata (=picensis), subgenus Munzia. In the presence of levulinic acid (LA),
      a competitive inhibitor of 5-aminolevulinic acid (ALA) dehydratase, ALA
      accumulated in the cotyledons and chlorophyll production was reduced in a
      stoichometric ratio. Accumulation of both Chl in untreated tissue and of ALA in
      seedlings incubated with LA is much more rapid in cotyledons with berteriana
      plastids than in those with odorata plastids. No difference was found between the
      inhibitor constants for LA of ALA dehydratase extracted from seedlings with
      either berteriana or odorata plastids. ALA formation is not limited by the
      availability of possible precursors. ALA dehydratase and the porphobilinogenase
      complex (PBGase) are present in abundance and in equal amounts in cotyledons with
      either berteriana or odorata plastids. It is concluded that the different
      capacities of the ALA synthesizing system fully account for the different rates
      of Chl formation in the seedlings with identical genomes and different plastid
      types. 

PMID- 24301970
TI  - Synchronous pressure-potential changes in the phloem of Fraxinus americana L.
AB  - Simultaneous measurement of the pressure potential of the phloem of F. americana
      made on two locations on the trunk over long periods of time showed synchronous
      oscillations of no fixed period during the day. The simultaneous changes in
      pressure in two different trees indicated environmental changes were responsible
      for the synchrony. The coincident changes of pressure 5 m apart on the same trunk
      implied that either transpiration had an immediate and direct effect upon the
      pressure potentials developed in the phloem because of the intimate relationship
      of the phloem water potential and the water potential of the adjacent
      transpiration stream, or factors affecting phloem loading resulted in pressure
      changes throughout the phloem. 

PMID- 24301971
TI  - Foliar flavonoid distribution during Spinacia chloroplast isolation.
AB  - The flavonoid glycoside accumulation level was compared in class A and in class C
      spinach chloroplast suspensions. Class A chloroplasts (up to 97% intact)
      contained about 0.4% of the total flavonoid glycosides present in leaves. Further
      purification of 97%-intact chloroplast suspensions, through a Percoll gradient,
      reduced the glycoside level to less than 0.15%. On the other hand, class C
      chloroplasts (100% broken plastids) contained between 10 to 30 times more
      flavonoids than intact Percoll purified chloroplasts. These results indicate that
      chloroplasts could bind vacuolar glycosides during their period of isolation.
      This hypothesis was confirmed by controlled contamination experiments using a
      cell-free supernatant as a source of vacuolar glycosides. Furthermore, the level
      of flavonoids in chloroplasts could be decreased to a level close to that
      obtained in intact Percoll purified chloroplasts by washing with soluble
      polyvinylpyrolidone. The results presented in this paper demonstrate the
      importance of maintaining the physiological integrity of plastids during the
      course of organelle isolation when investigating flavonic compartmentation in
      leaves. 

PMID- 24301972
TI  - Interactions between the branched-chain amino acids in the growth of Spirodela
      polyrhiza.
AB  - The joint action of L-valine and L-isoleucine, L-leucine and L-isoleucine, and L
      valine and L-leucine on the growth of Spirodela polyrhiza was established. The
      effect of one branched-chain amino acid on growth inhibition by another one was
      compared with the non-specific antagonisms which glycine and L-alanine exert on
      growth inhibition by singly supplied branched-chain amino acids. In this way
      specific and non-specific interactions could be distinguished. It appeared that:
      (1) L-isoleucine was a specific antagonist of L-valine; (2) L-leucine was a
      specific antagonist of L-isoleucine; (3) L-valine and L-leucine were synergistic
      growth inhibitors. Further, it was found that: (4) growth inhibition by L-leucine
      was specifically antagonized by simultaneously supplied L-valine and L
      isoleucine; (5) an excess of L-isoleucine strongly inhibited the conversion of
      exogenous valine into leucine; (6) accumulation of valine was typical of
      isoleucine-induced growth inhibition. The results are consistent with the view
      that growth inhibition by L-valine and L-leucine is due to the blocking of
      acetohydroxy acid synthetase, the first common enzyme in the valine-isoleucine
      biosynthetic pathway. Growth inhibition by L-isoleucine, however, seems to result
      from inhibition of leucine synthesis at a step after 2-oxoisovaleric acid. Some
      aspects of the regulation of branched-chain amino acid biosynthesis in higher
      plants are discussed. 

PMID- 24301973
TI  - Enzymatic ethylene formation from 1-aminocyclopropane-1-carboxylic acid by
      manganese, a protein fraction and a cofactor of etiolated pea shoots.
AB  - The cofactor of enzymatic, 1-aminocyclopropane-1-carboxylic acid dependent
      ethylene formation was concentrated on cation exchange columns. When chelators of
      cations were added to the homogenates, cofactor activity was lost. Cofactor
      fractions were partly resistant to oxidation at 600 degrees  C. Mn(2+)
      substituted for the cofactor in ethylene formation from 1-aminocyclopropane-1
      carboxylic acid by a protein fraction isolated from etiolated pea shoots. In
      addition, Mn(2+) enhanced the stimulatory effect of the concentrated cofactor.
      The elution volume for the cofactor on a Sephadex G-25 column was lower than that
      of MnCl2. In paper electrophoresis the cofactor migrated to the cathode at pH
      10.8 and 2.2. The RF of cofactor on cellulose plates developed in butanol: acetic
      acid: H2O was 0.4. After cellulose chromatography, cofactor activity had to be
      reconstituted by the addition of MnCl2. Chelators, anti-oxidants, and catalase
      were inhibitors of Mn(2+)-cofactor-dependent ethylene formation. The protein
      necessary for 1-aminocyclopropane-1-carboxylic acid dependent ethylene formation
      in vitro was seperated from 95-98% of the total protein in homogenates by DE-52
      cellulose chromatography and (NH4)2SO4-fractionation. 

PMID- 24301974
TI  - Rapidly induced ethylene formation after wounding is controlled by the regulation
      of 1-aminocyclopropane-1-carboxylic acid synthesis.
AB  - Bean leaves from Phaseolus vulgaris L. var. Pinto 111 react to mechanical
      wounding with the formation of ethylene. The substrate for wound ethylene is 1
      aminocyclopropane-1-carboxylic acid (ACC). It is not set free by
      decompartmentation but is newly synthesized. ACC synthesis starts 8 to 10 min
      after wounding at 28 degrees C, and 15 to 20 min after wounding at 20 degrees C.
      Aminoethoxyvinylglycine (AVG), a potent inhibitor of ethylene formation from
      methionine via ACC, inhibits wound ethylene synthesis by about 95% when applied
      directly after wounding (incubations at 20 degrees C). AVG also inhibits the
      accumulation of ACC in wounded tissue. AVG does not inhibit conversion of ACC to
      ethylene. Wound ethylene production is also inhibited by cycloheximide, n-propyl
      gallate, and ethylenediaminetetraacetic acid. 

PMID- 24301975
TI  - Studies on the growth and development of protoplasts of the moss, Physcomitrella
      patens, and its control by light.
AB  - Protoplasts prepared from protonemal cultures of the moss Physcomitrella patens
      begin to regenerate a new cell wall within 1 h of removal from cellulase. The
      wall is seen as a gradually thickening mat of fibres when examined by scanning
      electron microscopy. Development of filaments from protoplasts takes place in the
      majority of cases only after one or more cell divisions have occurred. The
      direction of emergence of filaments is random in uniform light, but strongly
      negatively phototropic in bright unidirectional horizotal light. Filament growth
      is also strongly negatively phototropic. The influence of unidirectional light
      can be destroyed by incubating protoplasts in the presence of colchicine.
      Filaments growing in unidirectional light have cytoplasmic microtubules running
      along their long axes and in close association with large organelles. These
      results are discussed in terms of the potential for this system for the study of
      polarity in plants. 

PMID- 24301976
TI  - Freezing injury in cold-acclimated and unhardened spinach leaves : I.
      Photosynthetic reactions of thylakoids isolated from frost-damaged leaves.
AB  - Spinach plants (Spinacia oleracea L.) were frost-hardened by cold-acclimation to
      1 degrees  C or kept in an unhardy state at 20 degrees /14 degrees  C in
      phytotrons. Detached leaves were exposed to temperatures below 0 degrees C. Rates
      of photosynthetic CO2 uptake by the leaves, recorded after frost treatment,
      served as a measure of freezing injury. Thylakoid membranes were isolated from
      frost-injured leaves and their photosynthetic activities tested. Ice formation
      occurred at about-4 degrees  to-5 degrees  C, both in unhardened and cold
      acclimated leaves. After thawing, unhardened leaves appeared severely damaged
      when they had been exposed to-5 degrees  to-8 degrees  C. Acclimated leaves were
      damaged by freezing at temperatures between-10 degrees  to-14 degrees  C. The
      pattern of freezing damage was complex and appeared to be identical in hardened
      and unhardened leaves: 1. Inactivation of photosynthesis and respiration of the
      leaves occurred almost simultaneously. 2. When the leaves were partly damaged,
      the rates of photosynthetic electron transport and noncyclic photophosphorylation
      and the extent of light-induced H(+) uptake by the isolated thylakoids were
      lowered at about the same degree. The dark decay of the proton gradient was,
      however, not stimulated, indicating that the permeability of the membrane to-ward
      protons and metal cations had not increased. 3. As shown by partial reactions of
      the electron transport system, freezing of leaves predominantly inhibited the
      oxygen evolution, but photosystem II and photosystem I-dependent electron
      transport were also impaired. 4. Damage of the chloroplast envelope was indicated
      by a decline in the percentage of intact chloroplasts found in preparations from
      injured leaves. The results are discussed in relation to earlier studies on
      freezing damage of thylakoid membranes occurring in vitro. 

PMID- 24301977
TI  - Freezing injury in cold-acclimated and unhardened spinach leaves : II. Effects of
      freezing on chlorophyll fluorescence and light scattering reactions.
AB  - Leaves from cold-acclimated and from unhardened spinach plants (Spinacia oleracea
      L.) were subjected to a freezing/thawing procedure in which varying minimum
      temperatures were reached. Subsequently, the chlorophyll fluorescence induction
      signal (Kautsky phenomenon) and the light-induced apparent absorbance changes at
      535 nm (light-scattering changes indicative of the proton gradient, and
      absorbance changes induced by the membrane potential) of the leaves were studied
      to obtain information on the course and mechanism of frost damage to the
      photosynthetic apparatus. Membrane energization as indicated by these signals was
      related in a complex way to the inactivation of CO2 assimilation due to the
      progressing impact of freezing: In the absence of CO2, the maximum energization
      of the thylakoids was progressively decreased. According to altered fluorescence
      signals, the electron transport system was affected in parallel. In the presence
      of CO2, energization frequently appeared increased when the leaves had been
      partially damaged, i.e., when the CO2 assimilation rates were lowered. The
      results suggest that the primary frost injury in chloroplasts of intact leaves
      consists of an inhibition of the energy conserving photosynthetic processes and,
      in addition, of a partial inactivation of the carbon reduction cycle. The pattern
      of freezing injury was no different in frost-hardened and unhardened leaves. 

PMID- 24301978
TI  - On the biogenesis of cytokinins in roots of Phaseolus vulgaris.
AB  - Roots of intact bean plants were supplied with [(14)C]adenine by pulse-chase
      experiments. The rate of incorporation of radioactivity into tRNA and
      oligonucleotides of roots as well as the content of radioactive labeled cytokinin
      nucleotides in these RNA fractions were determined. On the average, 1/70 of the
      radioactivity incorporated into tRNA was localized in
      N(6)(Delta(2)isopentenyl)adenosine. The half life of tRNA was estimated to be 65
      70 h. Shortly after the pulse period, oligonucleotides contained zeatin riboside
      at a ratio of 1:800, on the basis of radioactivity. The half life of these
      oligonucleotides was determined to be about 8 h. The main free radioactive
      cytokinin of roots and leaves was zeatin. Comparing the rate of degradation of
      (14)C-labeled tRNA and the oligonucleotides of roots and the rate of appearance
      of radioactive cytokinins in roots and leaves, we found strong indications for
      their dependency. The results contradict the hypothesis of de novo synthesis of
      cytokinins in roots of intact bean plants. 

PMID- 24301979
TI  - Carotenoid metabolism during chloroplast to chromoplast transformation in
      Capsicum annuum fruit.
AB  - Lipid and carotenoid metabolism associated with the structural transformations of
      the plastids during the ripening of Capsicum annuum fruits were studied. The
      early ripening stage is characterized by chloroplasts with a typical grana
      intergranal structure and a highly developed peripheral reticulum. At a later
      stage the thylakoid system is disintegrated and replaced by non-chlorophyllous
      single thylakoids, derived in part from the inner envelope membrane. First, these
      changes coincide with a loss of galactolipids, a slow increase in phospholipid
      content, a decrease in the ratio galactolipids/phospholipids and in the
      galactosyl transferase activities on a protein basis. Second, these changes
      correlate with an enhanced accumulation of keto-carotenoids. When the
      phospholipid environment is disturbed by difluorodinitrobenzene or
      phospholipases, the biosynthesis of phytoene, beta-carotene, and capsanthin is
      inhibited; phospholipase D has a greater effect. The role of a phospholipid
      environment in carotenoid biosynthesis is discussed. 

PMID- 24301980
TI  - Relationships between xanthoxin, phototropism, and elongation growth in the
      sunflower seedling Helianthus annuus L.
AB  - For phototropic curvature of a green sunflower seedling, only the hypocotyl has
      to be illuminated; the tip and cotyledons are not involved in stimulus
      perception. The etiolated seedling is phototropically insensitive, illumination
      of only the hypocotyl renders it sensitive. It is concluded that the
      photoreceptor is located within the responding organ. In curving seedlings, the
      endogenous indoleacetic acid (IAA) remains evenly distributed. However, the
      inhibitor, xanthoxin (Xa), accumulates on the illuminated side. The degree of
      phototropic response is generally related to the concentration of Xa. The amount
      of phototropic curvature is independent of the rate of elongation growth, the
      former can be changed without affecting the latter, and vice versa. The data
      conflict with the Cholodny-Went theory, whereas they support the hypothesis of
      Blaauw that the phototropic reaction is caused by the local accumulation of a
      growth-inhibiting substance on the irradiated side. 

PMID- 24301981
TI  - The biphasic fluence response of carotenogenesis in Neurospora crassa: Temporary
      insensitivity of the photoreceptor system.
AB  - Whether or not illumination is continuous or interrupted during the span in which
      increasing illumination time periods (i.e., increasing fluences) have no
      different effect on carotenogenesis is optional, in regard to the amount of
      carotenoids produced (revealing the plateau of the biphasic fluence response
      curve). This indicates temporary insensitivity. When the time delay between the
      onsets of the initial and second illumination is extended beyond the expanse of
      the plateau, the amount of carotenoids induced by the second illumination depends
      on the time elapsed following the first exposure; after ca. 2 h, maximum
      competence for a second induction is completely restored. On the other hand, the
      amount of carotenoids induced by a second illumination also depends on the
      duration of this second illumination, but, unlike the dependence in a single
      illumination, results in a different fluence response curve for the second
      exposure. When UV-A is used for induction, the refractory period which follows
      the first exposure seems to be the same as for blue light, suggesting vision of
      UV-A and blue light by the same photoreceptor system. 

PMID- 24301982
TI  - Photosynthesis of isolated chloroplasts and protoplasts under osmotic stress :
      Reversible swelling of chloroplasts by hypotonic treatment and its effect on
      photosynthesis.
AB  - 1. Isolated intact spinach chloroplasts respond to changes of the sorbitol
      concentration of the suspending medium as near-perfect osmometers within a large
      range of osmotic potentials. Under isotonic conditions (pi=9-10 bar), their
      average osmotic volume is 24 MUm(3) and the total volume 36 MUm(3). The osmotic
      volume can be increased to 63 MUm(3) by lowering the sorbitol concentration until
      a critical osmotic potential of pi=4 bar is reached. Below that value
      chloroplasts rupture. Between 10 bar and 4 bar, volume changes are reversible. 2.
      Increasing the chloroplast volume above 24 MUm(3) causes inhibition of
      photosynthesis, with 50% inhibition occurring at an osmotic potential of pi=5-6
      bar. This corresponds to an osmotic volume of 45-55 MUm(3). Depending on the
      duration of hypotonic treatment, inhibition of photosynthesis is more or less
      reversible. 3. Between 4 and 10 bar, the chloroplast envelope exhibits a very low
      permeability for ferricyanide, many metabolites, and soluble stroma proteins. 4.
      Electron transport is not inhibited by swelling of chloroplasts. Also, the
      ATP/ADP-ratio remains unchanged. 5. The solute concentration in the chloroplasts
      appears to be optimal for photosynthesis at 10 bar. Increasing the chloroplast
      volume causes inhibition of photosynthesis by dilution effects. 

PMID- 24301983
TI  - Biosynthesis of wax esters in tissues of Sinapis alba L. seeds.
AB  - The biosynthesis of wax esters has been investigated in maturing seeds of Sinapis
      alba. Exogenous long-chain alcohols are incorporated exclusively into alkyl
      moieties of wax esters. Oxidation of the long-chain alcohols is not detected.
      Exogenous fatty acids are incorporated into acyl moieties of wax esters to a low
      extent. A reduction of fatty acids to alcohols is not observed. Synthesis of wax
      esters is localized exclusively in the testa; both outer and inner integument are
      equally active in wax ester biosynthesis. The biosynthesis of wax esters is
      specific with regard to both chain length and degree of unsaturation of long
      chain alcohols. Exogenous and endogenous sterols are not esterified. 

PMID- 24301984
TI  - Changes in microfibril arrangement on the inner surface of the epidermal cell
      walls in the epicotyl of Vigna angularis ohwi et ohashi during cell growth.
AB  - Throughout the entire period of cell growth, the microfibrils on the inner
      surface of the outer tangential walls of the epidermal cells of Vigna angularis
      epicotyls are running parallel to one another and their orientation differs from
      cell to cell. Although transverse, oblique and longitudinal microfibrils can be
      observed irrespective of cell age, the frequency distribution of microfibril
      orientation changes with age. In young cells, transversely oriented microfibrils
      predominate. In cells of medium age, which are still undergoing elongation,
      transverse, oblique and longitudinal microfibrils are present in quite similar
      frequencies. In old, non-growing cells, longitudinally oriented microfibrils are
      predominent. A decrease in the relative frequency of transversely oriented
      microfibrils with cell age was also observed in the radial epidermal walls. 

PMID- 24301985
TI  - Effects of gibberellin and colchicine on microfibril arrangement in epidermal
      cell walls of Vigna angularis Ohwi et Ohashi epicotyls.
AB  - Gibberellic-acid (GA3) treatment of azukibean epicotyls resulted in alterations
      of the direction of newly deposited microfibrils, on the cell walls. Cells having
      transverse microfibrils on the inner surface of the wall were observed more
      frequently in GA3-treated epicotyls than in untreated or water-treated ones. This
      effect of GA3 was negated by simultaneously supplied colchicine. A crossed
      polylamellate structure was observed in the inner portion of the walls of GA3
      treated cells, but not in the inner portion of the walls of colchicine-treated
      cells. The wall formed under the influence of colchicine consisted of
      microfibrils running in the same direction. 

PMID- 24301986
TI  - Response to chilling of tomato mesophyll protoplasts.
AB  - Freshly isolated protoplasts from tomato leaves show two completely different
      responses to a chilling treatment of 12 h at 7 degrees  C prior to culture at 29
      degrees  C, depending on the presence or absence of glucose in the medium. In the
      culture medium with glucose as osmoticum, where the rate of cell divisions under
      optimal culture conditions is relatively high (about 20% plating efficiency),
      protoplasts were drastically injured by the chilling procedure and died. In the
      medium with mannitol as the osmoticum instead of glucose, where the plating
      efficiency even under optimal conditions is rather low (about 8%), protoplasts
      withstand the chilling procedure. More-over, after the chilling treatment when
      the protoplasts were transferred to the optimal culture temperature of 29 degrees
      C, the plating efficiency was raised to about 20%, which is the same level as in
      the glucose-containing medium without chilling. This effect was not observed when
      the medium in which the protoplasts were suspended during the chilling period was
      replaced with fresh medium. This suggests that under these conditions tomato
      protoplasts produce and excrete a factor in the cold that improves the vitality
      of the cells or stimulates cell division. The possible relationship between
      chilling sensitivity of tomato protoplasts and their ability to divide will be
      discussed. 

PMID- 24301987
TI  - Highly-Integrated CMOS Interface Circuits for SiPM-Based PET Imaging Systems.
AB  - Recent developments in the area of Positron Emission Tomography (PET) detectors
      using Silicon Photomultipliers (SiPMs) have demonstrated the feasibility of
      higher resolution PET scanners due to a significant reduction in the detector
      form factor. The increased detector density requires a proportionally larger
      number of channels to interface the SiPM array with the backend digital signal
      processing necessary for eventual image reconstruction. This work presents a CMOS
      ASIC design for signal reducing readout electronics in support of an 8*8 silicon
      photomultiplier array. The row/column/diagonal summation circuit significantly
      reduces the number of required channels, reducing the cost of subsequent
      digitizing electronics. Current amplifiers are used with a single input from each
      SiPM cathode. This approach helps to reduce the detector loading, while
      generating all the necessary row, column and diagonal addressing information. In
      addition, the single current amplifier used in our Pulse-Positioning architecture
      facilitates the extraction of pulse timing information. Other components under
      design at present include a current-mode comparator which enables threshold
      detection for dark noise current reduction, a transimpedance amplifier and a
      variable output impedance I/O driver which adapts to a wide range of loading
      conditions between the ASIC and lines with the off-chip Analog-to-Digital
      Converters (ADCs).

PMID- 24301988
TI  - Self quenching of chlorosome chlorophylls in water and hexanol-saturated water.
AB  - The optical properties of a methyl ester homolog of bacteriochlorophylld (BChld M
      ) and bacteriochlorophyllc (BChlc) in H2O, hexanol-saturated H2O and methanol
      were studied by absorption, fluorescence emission, and circular dichroism (CD).
      In H2O, BChld M spontaneously forms an aggregate similar to that formed in
      hexane, with absorption maximum at 730 nm and fluorescence emission at 748 nm.
      For the pigment sample in hexanol-saturated H2O, while the absorption peaks at
      661 nm, only slightly red-shifted compared to the monomer, the fluorescence
      emission is highly quenched. When diluted 2-3 fold with H2O, the absorption
      returns to around 720 nm, characteristic of an aggregate. The CD spectrum of the
      H2O aggregate exhibits a derivative-shaped feature with positive and negative
      peaks, while the amplitude is lower than that of chlorosomes. The Fourier
      transform infrared spectra of BChld M aggregates in H2O and hexane were measured.
      A 1644 cm(-1) band, indicative of a bonded 13(1)-keto group, is detected for both
      samples. A marker band for 5-coordinated Mg was observed at 1611 cm(-1) for the
      two samples as well. To study the kinetic behavior of the samples, both single
      photon counting (SPC) fluorescence and transient absorption difference
      spectroscopic measurements were performed. For BChld M in hexanol-saturated H2O,
      a fast decay component with a lifetime of 10 to 14 ps was detected using the two
      different techniques. The fast decay could be explained by the concentration
      quenching phenomenon due to a high local pigment concentration. For the pigment
      sample in H2O, SPC gave a 16 ps component, whereas global analysis of transient
      absorption data generated two fast components: 3.5 and 26 ps. The difference may
      arise from the different excitation intensities. With a much higher excitation in
      the latter measurements, other quenching processes, e.g. annihilation, might be
      introduced, giving the 3.5 ps component. Finally, atomic force microscopy was
      used to examine the ultrastructure of BChld M in H2O and hexanol-saturated H2O.
      Pigment clusters with diameters ranging from 15 to 45 nm were observed in both
      samples. 

PMID- 24301989
TI  - The role of transmembrane electrochemical potential and phosphorylation of PS II
      proteins in temperature induced light emission from ATP-treated lettuce
      thylakoids.
AB  - Changes in characteristics of flash-induced thermoluminescence (TL) glow curves
      in thylakoids of lettuce following incubation of the organelles with ATP, under
      illumination or in the dark, were investigated. TL bands were induced by 1 or 2
      flashes fired at -10 degrees C or 1 degrees C in thylakoids: TL curves in control
      thylakoids which were dark-adapted or submitted to an illumination without ATP,
      can be deconvoluted as the sum of one single B band and minor contributions. In
      thylakoids incubated for 90 s with 0.5 mM ATP, either under light or in the dark
      (after a 90 s preillumination), bands presented complex shapes; after
      deconvolution, they appeared composed of a B band with a low Ea (activation
      energy): 0.6 e.v. as compared to 0.75 in control, and a supplementary band
      peaking at about 10 degrees C. The band at low temperature was suppressed by low
      concentrations (10-20 nM) of valinomycin, nigericin or FCCP as well as by 10 mM
      ammonium chloride, leaving B bands with the same characteristics as in control
      material. Finally with higher nigericin concentrations, the bands became single B
      bands with high Ea (0.9 e.v.). These characteristics would define 3 different
      energized states (in the form of a transmembrane electrochemical potential) for
      thylakoids based upon the presence of the 10 degrees C band and the value of the
      activation energy for the B band component. The presence of a large 10 degrees C
      band was also correlated to the existence of a larger transmembrane pH gradient,
      in the dark, after an ATP-treatment, than in controls. The 10 degrees C band was
      specifically suppressed by the action of low concentrations of alkaline
      phosphatase with minor changes in characteristics of the remaining B band
      suggesting that phosphorylation of PS II proteins is also involved in the
      appearance of this low temperature band. The main mechanism at the origin of the
      low temperature band would be a destabilization of S2/3QB (-) charge pairs in
      energized membranes. 

PMID- 24301990
TI  - Purification and properties of glycolate oxidase from plants with different
      photosynthetic pathways: Distinctness of C4 enzyme from that of a C 3 species and
      a C 3-C 4 intermediate.
AB  - Glycolate oxidase (GO; EC 1.1.3.1) was purified from the leaves of three plant
      species:Amaranthus hypochondriacus L.(NAD-ME type C4 dicot),Pisum sativum L. (C3
      species) andParthenium hysterophorus L. (C3-C4. intermediate). A flavin moiety
      was present in the enzyme from all the three species. The enzyme from the C4
      plant had a low specific activity, exhibited lower KM for glycolate, and required
      a lower pH for maximal activity, compared to the C3 enzyme. The enzyme from the
      C4 species oxidized glyoxylate at <10% of the rate with glycolate, while the GO
      from the C3 plant oxidized glyoxylate at a rate of about 35 to 40% of that with
      glycolate. The sensitivity of GO from C4 plant to alpha-hydroxypyridinemethane
      sulfonate, 2-hydroxy-3-butynoate and other inhibitors was less than that of the
      enzyme from C3 source. The properties of GO fromParthenium hysterophorus, were
      similar to those of the enzyme fromPisum sativum. The characteristics of
      glycolate oxidase from leaves of a C4 plant,Amaranthus hypochondriacus are
      different from those of the C3 species or the C3-C4 intermediate. 

PMID- 24301991
TI  - Leaf development and phytochrome modulate the activation ofpsbD-psbC
      transcription by high-fluence blue light in barley chloroplasts.
AB  - Activation ofpsbD transcription by light assists in maintaining the synthesis of
      the PS II reaction center protein, D2, which is photodamaged in plants exposed to
      high light. In this study, the photosensory pathways and mechanisms that regulate
      the expression of thepsbD-psbC light-responsive promoter, LRP, were investigated
      during barley (Hordeum vulgare L.) seedling development. Accumulation ofpsbD-psbC
      mRNAs in response to light was observed in apical sections of primary leaves with
      little or no increase in mRNAs in basal sections. In both 4.5- and 7.5-day-old
      etiolated seedlings, blue light was most effective for activating mRNA
      accumulation from thepsbD-psbC LRP. However, the response of the LRP to red light
      increased 7-fold in 7.5-day relative to 4.5-day-old seedlings. Blue light
      preferentially activatedpsbD-psbC transcription, while red light was most
      effective for activating total plastid transcription and the expression of genes
      encoding the small (RbcS) and large (rbcL) subunits of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and Chl-a/b-binding protein (Lhcb). The stimulatory effects
      of red light onpsbD-psbC expression were partially reversed, and of blue light
      were not reversed, by subsequent pulses of far-red light. In contrast, continuous
      far-red light given together with blue light enhancedpsbD-psbC transcription in a
      synergistic manner. These observations indicate that phytochrome modulates the
      effects of high-fluence blue light onpsbD-psbC transcription by affecting total
      plastid transcription. 

PMID- 24301992
TI  - Chromatic regulation inChlamydomonas reinhardtii alters photosystem stoichiometry
      and improves the quantum efficiency of photosynthesis.
AB  - The work addressed the adjustment of the photosystem ratio in the green
      algaChlamydomonas reinhardtii. It is shown that green algae, much like
      cyanophytes and higher plants, adjust and optimize the ratio of the two
      photosystems in chloroplasts in response to the quality of irradiance during
      growth. Such adjustments are compensation reactions and helpC. reinhardtii to
      retain a quantum efficiency of oxygen evolution near the theoretical maximum.
      Results show variable amounts of PS I and a fairly constant amount of PS II in
      chloroplasts and suggest that photosystem stoichiometry adjustments, occurring in
      response to the quality of irradiance during plant growth, are mainly an
      adjustment in the concentration of PS I. The work delineates chromatic effects on
      chlorophyll accumulation in the chloroplast ofC. reinhardtii from those
      pertaining to the regulation of the PS I/PS II ratio. The detection of the
      operation of a molecular feedback mechanism for the PS I/PS II ratio adjustment
      in green algae strengthens the notion of the highly conserved nature of this
      mechanism among probably all oxygen evolving photosynthetic organisms. Findings
      in this work are expected to serve as the basis of future biochemical and
      mutagenesis experiments for the elucidation of the photosystem ratio adjustment
      in oxygenic photosynthesis. 

PMID- 24301993
TI  - Localization of light-harvesting complex apoproteins in the chloroplast and
      cytoplasm during greening ofChlamydomonas reinhardtii at 38 degrees C.
AB  - Assembly of the major light-harvesting complex (LHC II) and development of
      photosynthetic function were examined during the initial phase of thylakoid
      biogenesis inChlamydomonas reinhardtii cells at 38 degrees C. Continuous
      monitoring of LHC II fluorescence showed that these processes were initiated
      immediately upon exposure of cells to light. However, mature-size apoproteins of
      LHC II (Lhcb) increased in amount in an alkali-soluble (non-membrane) fraction in
      parallel with the increase in the membrane fraction. Alkali-soluble Lhcb were not
      integrated into membranes when protein synthesis was inhibited, suggesting that
      they were not active intermediates in LHC II assembly, nor were they recovered in
      a purified chloroplast preparation. Immunocytochemical analysis of greening cells
      revealed Lhcb inside the chloroplast near the envelope and in clusters deeper in
      the organelle. Antibody binding also detected Lhcb in granules within vacuoles in
      the cytosol, and Lhcb were recovered in granules purified from greening cells.
      Our results suggest that the cytosolic granules serve as receptacles of Lhcb
      synthesized in excess of the amount that can be accommodated by thylakoid
      membrane formation within the plastid envelope. 

PMID- 24301994
TI  - The effect of free air carbon dioxide enrichment (FACE) and soil nitrogen
      availability on the photosynthetic capacity of wheat.
AB  - A simple system for free air carbon dioxide enrichment (FACE) was recently
      developed and it is here briefly described. Such a MiniFACE system allowed the
      elevation of CO2 concentration of small field plots avoiding the occurrence of
      large spatial and temporal fluctuations. A CO2 enrichment field experiment was
      conducted in Italy in the season 1993-1994 with wheat (cv. Super-dwarf Mercia). A
      randomized experimental design was used with the treatment combination CO2 * soil
      N, replicated twice. Gas exchange measurements showed that photosynthetic
      capacity was significantly decreased in plants exposed to elevated CO2 and grown
      under nitrogen deficiency. Photosynthetic acclimation was, in this case, due to
      the occurrence of reduced rates of rubP saturated and rubP regeneration limited
      photosynthesis. Gas exchange measurements did not instead reveal any significant
      effect of elevated CO2 on the photosynthetic capacity of leaves of plants well
      fertilized with nitrogen, in spite of a transitory negative effect on rubP
      regeneration limited photosynthesis that was detected to occur in the central
      part of a day with high irradiance. It is concluded that the levels of nitrogen
      fertilization will play a substantial role in modulating CO2 fertilization
      effects on growth and yields of wheat crops under the scenario of future climate
      change. 

PMID- 24301995
TI  - Can Photosystem II be a photogenerator of low potential reductant for CO2
      fixation and H 2 photoevolution?
AB  - The experimental grounds of the hypothesis of a single-light-reaction in oxygenic
      photosynthesis as suggested by Greenbaum et al. (Nature (1995) 376: 438-441) are
      critically discussed and a possible explanation of their data by Photosystem I
      contamination in the mutant utilized is argued. 

PMID- 24301996
TI  - Large scale preparations of photosynthetic catalysts from cyanobacteria.
AB  - Large scale preparations of photosynthetic catalysts from cyanobacteria afford
      special advantages in the discovery and the study of these proteins. Here, we
      present information on obtaining cyanobacteria from laboratory cultivation,
      commercial sources and from natural blooms. Procedures for the breakage and
      fractionation of large amounts of cells are reviewed. Since much of this
      information is not of a conventional sort, it may provide special help when the
      need for a large amount of a specific protein arises. 

PMID- 24301998
TI  - Compromise formation in social conflicts: The influence of age, issue, and
      interpersonal context.
AB  - Adolescents' understanding of societal conflict and of compromise resolution in
      the context of peer and authority relations was investigated. Six conflict
      stories were prepared for three social issues. Each issue included two similar
      stories that were counterbalanced for presentation in peer or authority context.
      The adolescents-ages 11, 13, 15, and 17-were asked to develop dialogues by
      continuing conversations from the stories with the aim of resolving the conflict.
      Responses were categorized on a 3-point scale: (1) noncompromise, (2) routine
      compromise, and (3) constructive compromise. In addition, one moral and one
      political dilemma were presented in order to relate conflict resolution to moral
      and political development. The major findings were an increase in frequency of
      constructive compromise with age and in peer vs authority context. Further, both
      moral and political development were significantly related to conflict resolution
      scores in peer but not in authority context. Results corroborate an
      interpretation that considers peer communicative relations of mutual respect and
      cooperation as a primary path to mature stages of social reasoning. 

PMID- 24301997
TI  - Membrane vesicles fromSynechocystis 6803 showing proton and electron transport
      and high ATP synthase activities.
AB  - A simple procedure for the preparation of well-coupled and stable membrane
      vesicles from the transformable cyanobacteriumSynechocystis 6803 is described
      with the primary aim of producing vesicles suitable for the study of
      photosynthetic electron transport and phosphorylation. Spheroplasts were obtained
      from the cyanobacterium by lysozyme treatment and stored untill prior to
      measurement, thylakoid vesicles were obtained by osmotic shock. These vesicles
      showed very high and stable ATP synthesis rates either driven by light or by acid
      base transition, and also performed light-induced ATP hydrolysis and linear
      electron transport. Formation of a proton gradient is studied by aminoacridines. 

PMID- 24301999
TI  - Inferencing and television: A developmental study.
AB  - Little research has been done to examine the cognitive processes engaged by
      television viewing in general, and with adolescent viewers in particular. The
      present study examined the extent of inferencing in adolescents' and young
      adults' interpretations of 3-min video segments taken from prime-time drama
      series and from rock music videos. It was predicted, and the results confirmed,
      that the less structured music video segments resulted in higher level
      inferencing than prime-time dramas. It was also found that young adults produced
      more higher-level inferences than adolescents, and prime-time drama led to more
      fact-based responses than music video. Correlations between television
      inferencing and scores on the Peel Lack of Closure Test were also examined to see
      if inferencing from video and from written text were related. Generally, these
      correlations were nonsignificant, confirming the hypotheses of other researchers
      that video inferencing involves unique knowledge structures that warrant further
      investigation. 

PMID- 24302001
TI  - Work and leisure relationships: An exploration of life possibilities during
      adolescence.
AB  - This study explored the relationship between leisure preferences and
      work/occupational aspiration for adolescents in Singapore and Australia. Three
      hypothesized relationships between the domains of "spillover", "compensation",
      and "segmentation" were investigated. Except for females in the Australian
      sample, it appeared that adolescents saw leisure preferences and occupational
      aspirations as two independent spheres of their personal futures, supporting the
      segmentation hypothesis. 

PMID- 24302000
TI  - The etiology of adolescents' perceptions of their weight.
AB  - The present study examined adolescents' actual and perceived weights in relation
      to why adolescents think they weigh what they do, where adolescents obtain weight
      control information, and adolescents' weight locus of control. The study was
      conducted in a Midwestern high school, based on information obtaind from 194
      freshmen. Thirty percent of the adolescents perceived their weight category
      inaccurately when compared to their actual weight and height. One-third of those
      who were thin, one-half of those who were normal weight, and two-thirds of those
      who were heavy had been exercising during the past six months to control or lose
      weight. Six percent of the thin, 41% of the normal weight, and 56% of the heavy
      students had dieted within the past six months to control or lose weight. The
      leading sources of weight control information were television, family, friends,
      and magazines. Teachers were identified as sources of information by less than
      10% of the students. Mother, family, and friends were identified as those most
      helpful in adolescents' attempts to lose weight. Significant chi-square
      differences were found between weight locus of control orientations and actual
      and perceived weight categories. Finally, a multivariate analysis of variance was
      used to analyze adolescents' perceptions of weighing what they do. Eat too much
      vs too little and exercise too much vs too little were the two reasons identified
      that were statistically significant. The information obtained from this study may
      be useful in designing and implementing weight control and nutritional programs
      for adolescents. For many of the adolescents, their perceptions were different
      from reality. 

PMID- 24302002
TI  - An analysis of the effects of gender on outcome in group treatment with young
      adolescents.
AB  - This study investigated the ways in which the gender of group leader and client
      might affect treatment outcome with young adolescents. Seventh- and eighth-grade
      students were involved in programs for enhancing social competence. Mixed-sex
      groups of adolescents received treatment from either male or female group
      leaders. Results revealed gender differences between the male and female
      adolescents on the outcome measures, no difference on outcome due to leader
      gender, and one interaction effect on a measure of social skills between
      adolescent gender and group leader gender. Acquisition of social skills, which
      takes place through modeling and observation, may be influenced by matched gender
      between leaders and adolescents; however, other competencies and abilities do not
      appear sensitive to leader and adolescent gender. 

PMID- 24302003
TI  - Hepatocyte growth factor regulates neovascularization in developing fat pads.
AB  - In this study, we used lentiviral-delivered shRNA to generate a clonal line of
      3T3-F442A preadipocytes with stable silencing of hepatocyte growth factor (HGF)
      expression and examined the long-term consequence of this modification on fat pad
      development. HGF mRNA expression was reduced 94%, and HGF secretion 79% (P <
      0.01), compared with preadipocytes treated with nontargeting shRNA. Fat pads
      derived from HGF knockdown preadipocytes were significantly smaller (P < 0.01)
      than control pads beginning at 3 days postinjection (0.022 +/- 0.003 vs. 0.037 +/
      0.004 g), and further decreased in size at day 7 (0.015 +/- 0.004 vs. 0.037 +/-
      0.003 g) and day 14 (0.008 +/- 0.002 vs. 0.045 +/- 0.007 g). Expression of the
      endothelial cell genes TIE1 and PECAM1 increased over time in control fat pads
      (1.6 +/- 0.4 vs. 11.4 +/- 1.7 relative units at day 3 and 14, respectively; P <
      0.05) but not in HGF knockdown fat pads (1.1 +/- 0.5 vs. 5.9 +/- 2.2 relative
      units at day 3 and 14). Contiguous vascular structures were observed in control
      fat pads but were much less developed in HGF knockdown fat pads. Differentiation
      of preadipocytes to mature adipocytes was significantly attenuated in HGF
      knockdown fat pads. Fat pads derived from preadipocytes with knockdown of the HGF
      receptor c-MET were smaller than control pads at day 3 postinjection (0.034 +/-
      0.002 vs. 0.049 +/- 0.004 g; P < 0.05), and remained the same size through day
      14. c-MET knockdown fat pads developed a robust vasculature, and preadipocytes
      differentiated to mature adipocytes. Overall these data suggest that preadipocyte
      secreted HGF is an important regulator of neovascularization in developing fat
      pads. 

PMID- 24302005
TI  - Pre-suckling calcium supplementation effectively prevents lactation-induced
      osteopenia in rats.
AB  - During lactation, osteoclast-mediated bone resorption and intestinal calcium
      hyperabsorption help provide extra calcium for lactogenesis. Since the suckling
      induced surge of pituitary prolactin (PRL) rapidly stimulates calcium absorption
      in lactating rats, it is hypothesized that pre-suckling oral calcium
      supplementation should be an efficient regimen to shift the calcium source from
      bone to diet, thereby slowing lactation-induced osteopenia. Our results showed
      that 30-min suckling markedly stimulated maternal duodenal calcium transport,
      which returned to the baseline at 45 min. Lactating rats given 4 mg/kg per dose
      calcium via a gavage tube at 90 min pre-suckling 4 doses a day for 14 days
      prevented a decrease in bone mineral density (BMD) of long bones and vertebrae.
      On the other hand, a single-dose supplementation, despite the same amount of
      calcium per day, appeared less effective. Because glucose and galactose further
      stimulated duodenal calcium transport in lactating rats, pre-suckling calcium
      supplement containing both sugars successfully normalized plasma ionized calcium
      and led to better bone gain than that with calcium alone. A histomorphometric
      study revealed that lactating rats given pre-suckling calcium plus monosaccharide
      supplement manifested greater trabecular bone volume and thickness and exhibited
      less eroded surface than in vehicle-treated lactating rats. Beneficial effects of
      the 14-day calcium supplementation persisted until 6 mo postweaning in dams and
      also elevated the baseline BMD of the offspring. In conclusion, our proof-of
      concept study has corroborated that pre-suckling calcium supplements, especially
      regimens containing monosaccharides, are efficient in preventing osteopenia in
      lactating rats and could increase bone density in both breastfeeding mothers and
      neonates. 

PMID- 24302004
TI  - Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic
      insulin resistance induced by excess amino acids.
AB  - Nutrient overload is associated with the development of obesity, insulin
      resistance, and type 2 diabetes. However, the underlying mechanisms for
      developing insulin resistance in the presence of excess nutrients are
      incompletely understood. We investigated whether activation of AMP-activated
      protein kinase (AMPK) prevents the hepatic insulin resistance that is induced by
      the consumption of a high-protein diet (HPD) and the presence of excess amino
      acids. Exposure of HepG2 cells to excess amino acids reduced AMPK
      phosphorylation, upregulated Notch1 expression, and impaired the insulin
      stimulated phosphorylation of Akt Ser(473) and insulin receptor substrate-1 (IRS
      1) Tyr(612). Inhibition of Notch1 prevented amino acid-induced insulin
      resistance, which was accompanied by reduced expression of Rbp-Jk, hairy and
      enhancer of split-1, and forkhead box O1. Mechanistically, mTORC1 signaling was
      activated by excess amino acids, which then positively regulated Notch1
      expression through the activation of the signal transducer and activator of
      transcription 3 (STAT3). Activation of AMPK by metformin inhibited mTORC1-STAT3
      signaling, thereby preventing excess amino acid-impaired insulin signaling.
      Finally, HPD feeding suppressed AMPK activity, activated mTORC1/STAT3/Notch1
      signaling, and induced insulin resistance. Chronic administration of either
      metformin or rapamycin inhibited the HPD-activated mTORC1/STAT3/Notch1 signaling
      pathway and prevented hepatic insulin resistance. We conclude that the
      upregulation of Notch1 expression by hyperactive mTORC1 signaling is an essential
      event in the development of hepatic insulin resistance in the presence of excess
      amino acids. Activation of AMPK prevents amino acid-induced insulin resistance
      through the suppression of the mTORC1/STAT3/Notch1 signaling pathway. 

PMID- 24302006
TI  - Weight cycling promotes fat gain and altered clock gene expression in adipose
      tissue in C57BL/6J mice.
AB  - Repeated attempts to lose weight by temporary dieting may result in weight
      cycling, eventually further gain of body fat, and possible metabolic adaptation.
      We tested this with a controlled experiment in C57BL/6J mice subjected to four
      weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding
      (LF). To search for genes involved in an adaptive mechanism to former weight
      cycling and avoid acute effects of the last cycle, the last hypercaloric feeding
      period was prolonged by an additional 2 wk before euthanization. Total energy
      intake was identical in WC and HF. However, compared with HF, the WC mice gained
      significantly more total body mass and fat mass and showed increased levels of
      circulating leptin and lipids in liver. Both the HF and WC groups showed
      increased adipocyte size and insulin resistance. Despite these effects, we also
      observed an interesting maintenance of circulating adiponectin and free fatty
      acid levels after WC, whereas changes in these parameters were observed in HF
      mice. Global gene expression was analyzed by microarrays. Weight-cycled mice were
      characterized by a downregulation of several clock genes (Dbp, Tef, Per1, Per2,
      Per3, and Nr1d2) in adipose tissues, which was confirmed by quantitative PCR. In
      3T3-L1 cells, we found reduced expression of Dbp and Tef early in adipogenic
      differentiation, which was mediated via cAMP-dependent signaling. Our data
      suggest that clock genes in adipose tissue may play a role in metabolic
      adaptation to weight cycling. 

PMID- 24302007
TI  - Contributions of adipose tissue architectural and tensile properties toward
      defining healthy and unhealthy obesity.
AB  - The extracellular matrix (ECM) plays an important role in the maintenance of
      white adipose tissue (WAT) architecture and function, and proper ECM remodeling
      is critical to support WAT malleability to accommodate changes in energy storage
      needs. Obesity and adipocyte hypertrophy place a strain on the ECM remodeling
      machinery, which may promote disordered ECM and altered tissue integrity and
      could promote proinflammatory and cell stress signals. To explore these
      questions, new methods were developed to quantify omental and subcutaneous WAT
      tensile strength and WAT collagen content by three-dimensional confocal imaging,
      using collagen VI knockout mice as a methods validation tool. These methods,
      combined with comprehensive measurement of WAT ECM proteolytic enzymes,
      transcript, and blood analyte analyses, were used to identify unique
      pathophenotypes of metabolic syndrome and type 2 diabetes mellitus in obese
      women, using multivariate statistical modeling and univariate comparisons with
      weight-matched healthy obese individuals. In addition to the expected differences
      in inflammation and glycemic control, approximately 20 ECM-related factors,
      including omental tensile strength, collagen, and enzyme transcripts, helped
      discriminate metabolically compromised obesity. This is consistent with the
      hypothesis that WAT ECM physiology is intimately linked to metabolic health in
      obese humans, and the studies provide new tools to explore this relationship.

PMID- 24302008
TI  - Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and
      peptide YY3-36 in healthy overweight/obese humans.
AB  - Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic
      individuals. We aimed to determine whether these abnormalities are secondary to
      hyperglycemia. Ten healthy overweight/obese subjects (age: 56 +/- 3 yr; BMI: 30.3
      +/- 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the
      absence (control trial) and presence of experimental hyperglycemia (hyperglycemia
      trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and
      peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured
      throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the
      feeling of fullness were increased in the postprandial periods, whereas ghrelin
      was decreased. In the hyperglycemia trial, in which plasma glucose was increased
      to 11.2 +/- 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h)
      of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05),
      whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and
      ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher
      compared with the control trial. Furthermore, the incremental (Delta0-0.5, 4-4.5,
      and 8-8.5 h) ghrelin response to the first and third meals was higher in the
      hyperglycemia trial in contrast to control (Delta: 2.3 +/- 8.0, P = 0.05; Delta:
      14.4 +/- 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P =
      0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia.
      Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different
      polynomial functions between the trials. In conclusion, hyperglycemia abolishes
      meal-induced satiety and dysregulates postprandial responses of the gut hormones
      PYY3-36 and ghrelin in overweight/obese healthy humans. 

PMID- 24302010
TI  - GLP-1 increases microvascular recruitment but not glucose uptake in human and rat
      skeletal muscle.
AB  - The insulinotropic gut hormone glucagon-like peptide-1 (GLP-1) has been proposed
      to have effects on vascular function and glucose disposal. However, whether GLP-1
      is able to increase microvascular recruitment (MVR) in humans has not been
      investigated. GLP-1 was infused in the femoral artery in overnight-fasted,
      healthy young men. Microvascular recruitment was measured with real-time contrast
      enhanced ultrasound and leg glucose uptake by the leg balance technique with and
      without inhibition of the insulinotropic response of GLP-1 by coinfusion of
      octreotide. As a positive control, MVR and leg glucose uptake were measured
      during a hyperinsulinemic-euglycemic clamp. Infusion of GLP-1 caused a rapid
      increase (P < 0.05) of 20 +/- 12% (mean +/- SE) in MVR in the vastus lateralis
      muscle of the infused leg after 5 min, and MVR further increased to 60 +/- 8%
      above preinfusion levels by 60 min infusion. The effect was slightly slower but
      similar in magnitude in the noninfused contralateral leg, in which GLP-1
      concentration was within the physiological range. Octreotide infusion did not
      prevent the GLP-1-induced increase in MVR. GLP-1 infusion did not increase leg
      glucose uptake with or without octreotide coinfusion. GLP-1 infusion in rats
      increased MVR by 28% (P < 0.05) but did not increase muscle glucose uptake.
      During the hyperinsulinemic clamp, MVR increased ~40%, and leg glucose uptake
      increased 35-fold. It is concluded that GLP-1 in physiological concentrations
      causes a rapid insulin-independent increase in muscle MVR but does not affect
      muscle glucose uptake. 

PMID- 24302011
TI  - Highly efficient methane biocatalysis revealed in a methanotrophic bacterium.
AB  - Methane is an essential component of the global carbon cycle and one of the most
      powerful greenhouse gases, yet it is also a promising alternative source of
      carbon for the biological production of value-added chemicals. Aerobic methane
      consuming bacteria (methanotrophs) represent a potential biological platform for
      methane-based biocatalysis. Here we use a multi-pronged systems-level approach to
      reassess the metabolic functions for methane utilization in a promising bacterial
      biocatalyst. We demonstrate that methane assimilation is coupled with a highly
      efficient pyrophosphate-mediated glycolytic pathway, which under oxygen
      limitation participates in a novel form of fermentation-based methanotrophy. This
      surprising discovery suggests a novel mode of methane utilization in oxygen
      limited environments, and opens new opportunities for a modular approach towards
      producing a variety of excreted chemical products using methane as a feedstock. 

PMID- 24302012
TI  - An organic response.

PMID- 24302009
TI  - Sulfation of 25-hydroxycholesterol regulates lipid metabolism, inflammatory
      responses, and cell proliferation.
AB  - Intracellular lipid accumulation, inflammatory responses, and subsequent
      apoptosis are the major pathogenic events of metabolic disorders, including
      atherosclerosis and nonalcoholic fatty liver diseases. Recently, a novel
      regulatory oxysterol, 5-cholesten-3b, 25-diol 3-sulfate (25HC3S), has been
      identified, and hydroxysterol sulfotransferase 2B1b (SULT2B1b) has been
      elucidated as the key enzyme for its biosynthesis from 25-hydroxycholesterol
      (25HC) via oxysterol sulfation. The product 25HC3S and the substrate 25HC have
      been shown to coordinately regulate lipid metabolism, inflammatory responses, and
      cell proliferation in vitro and in vivo. 25HC3S decreases levels of the nuclear
      liver oxysterol receptor (LXR) and sterol regulatory element-binding proteins
      (SREBPs), inhibits SREBP processing, subsequently downregulates key enzymes in
      lipid biosynthesis, decreases intracellular lipid levels in hepatocytes and THP-1
      derived macrophages, prevents apoptosis, and promotes cell proliferation in liver
      tissues. Furthermore, 25HC3S increases nuclear PPARgamma and cytosolic
      IkappaBalpha and decreases nuclear NF-kappaB levels and proinflammatory cytokine
      expression and secretion when cells are challenged with LPS and TNFalpha. In
      contrast to 25HC3S, 25HC, a known LXR ligand, increases nuclear LXR and decreases
      nuclear PPARs and cytosol IkappaBalpha levels. In this review, we summarize our
      recent findings, including the discovery of the regulatory oxysterol sulfate, its
      biosynthetic pathway, and its functional mechanism. We also propose that
      oxysterol sulfation functions as a regulatory signaling pathway. 

PMID- 24302013
TI  - Skyrmionics in sight.

PMID- 24302015
TI  - Persistent spin coherence and bipolarons.

PMID- 24302016
TI  - Standardization should come first.

PMID- 24302017
TI  - More than spectroscopy.

PMID- 24302018
TI  - Focusing on the molecular scale.

PMID- 24302019
TI  - An agnostic approach.

PMID- 24302020
TI  - Is there more than meets the eye?

PMID- 24302021
TI  - The struggle for control.

PMID- 24302023
TI  - Protein machines: an open and shut cage.

PMID- 24302024
TI  - Molecular sensing: a universal receptor.

PMID- 24302025
TI  - Nanoelectromechanical systems: Tuning in to a graphene oscillator.

PMID- 24302029
TI  - Highly diastereoselective synthesis of 3-hydroxy-2,2,3-trisubstituted indolines
      via intramolecular trapping of ammonium ylides with ketones.
AB  - A Rh2(OAc)4-catalyzed diazo decomposition reaction of diazo esters with 2
      aminophenyl ketones is reported. A series of 3-hydroxy-2,2,3-trisubstituted
      indolines are produced in good yields with excellent diastereoselectivities via
      an intramolecular aldol-type trapping of ammonium ylides with ketone units. 

PMID- 24302031
TI  - Changing our minds.

PMID- 24302027
TI  - Topological properties and dynamics of magnetic skyrmions.
AB  - Magnetic skyrmions are particle-like nanometre-sized spin textures of topological
      origin found in several magnetic materials, and are characterized by a long
      lifetime. Skyrmions have been observed both by means of neutron scattering in
      momentum space and microscopy techniques in real space, and their properties
      include novel Hall effects, current-driven motion with ultralow current density
      and multiferroic behaviour. These properties can be understood from a unified
      viewpoint, namely the emergent electromagnetism associated with the non-coplanar
      spin structure of skyrmions. From this description, potential applications of
      skyrmions as information carriers in magnetic information storage and processing
      devices are envisaged. 

PMID- 24302032
TI  - Spiritual issues in mental health care.
AB  - Religious and spiritual issues in mental health are explored in the context of
      four conceptual models: the medical, the nursing, the humanistic, and the
      pastoral. This is done by looking at each model in terms of content, diagnostic
      focus, language and treatment goals, and primary qualities in the health
      provider.The models are illustrated by case studies gathered from a
      multidisciplinary setting. The discovery that each model can incorporate the
      religious and spiritual dimension in mental health care, but that each model does
      this in distinctive ways, is a key point. 

PMID- 24302033
TI  - Spirituality and depth psychology.
AB  - The resurgence of interest in spiritual and religious matters and in the depth
      psychology of C.G. Jung is examined relative to the work of spiritual direction
      and pastoral counseling. It is suggested that the risks of muddled thinking,
      narcissism, gnosticism, and credulity are increased when one attempts to combine
      spiritual disciplines with depth psychology. 

PMID- 24302034
TI  - Keeping the therapist alive.
AB  - This article focuses on ways in which therapists can mamtain vitality in their
      work with people. Becoming more aware of personal dynamics, particularly of the
      need for control and power, is essential. To remain open to new theories and
      approaches avoids the pitfall of professional encapsulation. Experiencing the
      client as a person not only facilitates empathy but involves therapists in the
      growth process as well. Developing a tragic awareness of life enables therapists
      to maintain a sense of awe, wonder, and grace toward the human predicament, thus
      bringing "depth" or "spirituality" to their work. 

PMID- 24302035
TI  - Falling rings: Group and ritual process in a divorce.
AB  - This paper describes, analyzes, interprets, and spells out some implications of a
      divorce as it was faced and handled by a pastor and congregation. The challenge
      to work creatively with divorce came when both the husband and wife wished to
      remain in the congregation as members. The paper briefly sets forth theological
      perspectives on marriage, divorce, and discipline in the Mennonite Church, a
      brief case history of the couple, a description of the group and ritual process
      with which the pastor and congregation responded, and the reflections of the
      couple and members a year later. The paper offers not a model but, rather, a
      symbol as presented in the title, "Falling Rings." It is hoped that the symbol
      will not only give rise to thought, but will also spark the imagination so as to
      enable other congregations to respond more assertively, creatively, and caringly
      to those who divorce in their midst. 

PMID- 24302036
TI  - Wets, drys, and damps.
AB  - The real issues pertaining to beverage alcohol have been obscured by propaganda
      from America's "drys" and "wets." The Judeo-Christian culture has, throughout its
      history, usually advocated moderation. A similar position has been supported by
      Plato and by some modern researchers concerned with the prevention of alcoholism.
      Problem drinkers are more likely to come from a family tradition of abstinence
      than from moderate imbibers. 

PMID- 24302037
TI  - Nietzsche: An intellectual Nebuchadnezzar.
AB  - The essay introduces and defines the concept of "an intellectual Nebuchadnezzar"
      one who, despite his hostility to religion, serves God's purposes by the depth of
      his ideas. In terms of this notion, some of Friedrich Nietzsche's views are
      explored. Specifically, Nietzsche's perspective on artistic creativity is
      analyzed and applied to the notion of creativity in human relationships. In
      addition to concluding that Nietzsche is himself an "intellectual
      Nebuchadnezzar," the broader point is made that truth and insight should be
      welcomed by the religious community even if the source of that truth is one
      ostensibly hostile to religion. 

PMID- 24302038
TI  - Factors influencing distribution ofDiabrotica spp. in blossoms of
      cultivatedCucurbita spp.
AB  - Cultivars representing three species ofCucurbita were examined for blossom
      preference byDiabrotica spp.C. maxima cultivars were found to be preferred byD.
      undecimpunctata howardi over those ofC. pepo andC. moschata.D. virgifera
      virgifera preferredC. maxima and the "Connecticut Field" cultivar ofC. pepo.C.
      moschata and other cultivars ofC. pepo were not preferred. Cultivars were
      examined for differences in floral volatile release, blossom cucurbitacin
      content, and pollen content of male blossoms.C. maxima male blossoms released a
      larger quantity of volatiles thanC. pepo orC. moschata. Also, onlyC. maxima male
      blossoms contained cucurbitacins. Cultivars ofC. moschata contained the largest
      quantities of pollen, but all three species contained relatively large
      quantities. The data indicate a correspondence ofD. u. howardi distribution in
      the field with high volatile release rates and high cucurbitacin levels that are
      found inC. maxima blossoms.D. v. virgifera distribution appears to be somewhat
      independent of these factors since this species was abundant in blossoms of aC.
      pepo cultivar as well as cultivars ofC. maxima. 

PMID- 24302039
TI  - Field response of spruce bark beetle,Ips typographus, to aggregation pheromone
      candidates.
AB  - Six compounds previously identified from hindguts of unmated maleIps typographus
      (L.) during host colonization: 2-methyl-3-buten-2-ol (MB),cis-verbenol (cV),trans
      verbenol (tV), myrtenol (Mt),trans-myrtanol (tM), and 2-phenylethanol (PE), were
      tested for their attractivity in the field with a subtractive method. The amounts
      of MB and cV released from a pipe trap were similar to those given off from the
      commercial bait Ipslure as well as that from a Norway spruce tree,Picea abies
      (L.) Karst., under mass attack. The blend of the compounds became nonattractive
      when either MB or cV was subtracted, while subtraction of any of the other four
      compounds had no effect. Addition of ipsdienol (Id) to the blend did not
      significantly increase the attraction. In a second comparative test, the addition
      of three compounds as a group (tV + Mt + PE) to MB + cV again had no effect on
      the attraction, but the addition of Id increased the catch somewhat. Addition of
      host logs to a bait releasing MB + cV at a rate lower than in previous
      experiments did not influence the attraction to pipe traps. Sticky traps
      containing natural pheromone sources (50 males in a log), which released 1-5
      mg/day of MB as determined by aerations with deuterated MB as internal standard,
      were less attractive than a synthetic source releasing similar amounts of MB. 

PMID- 24302040
TI  - Human axillary extracts: Analysis of compounds from samples which influence
      menstrual timing.
AB  - Previous studies have shown that menstrual cycle length and fertility are
      affected by a regular pattern of either: (1) intimate contact with men; or (2)
      contact with extracts from male axillary secretions; and (3) the axillary
      extracts of women. Experiments utilizing axillary extracts employed a controlled,
      double-blind research design using either extract or placebo. The study reported
      here employed quantitative gas chromatography-mass spectrometry (GC-MS)
      techniques to determine the concentration of several steroids in the male and
      female axillary secretion extracts. The steroids examined were: androsterone
      sulfate, dehydroepiandrosterone sulfate, and the volatile steroid androstenol.
      The results suggest the following: (1) The concentration of androstenol produced
      by secretion donors varied during the collection period. Males appear to produce
      more androstenol at certain times; women's secretions show a menstrual variation
      in androstenol; the highest concentrations of this compound appear to be produced
      in the midfollicular phase, prior to ovulation. (2) The concentration of
      dehydroepiandrosterone sulfate is significantly greater in men than in women. (3)
      In addition to the steroids, a series of aliphatic acids which range from C2 to
      C18 in chain length were found. The more volatile members of this series may
      contribute to the odor of the secretions. 

PMID- 24302041
TI  - Male-produced aggregation pheromone in pea and bean weevil,Sitona lineatus (L.).
AB  - The attraction ofS. lineatus to live baits comprisingS. lineatus feeding onVicia
      faba (L.) was studied in a field experiment in the early spring. There was clear
      evidence that maleS. lineatus produced an aggregation pheromone which attracted
      approximately equal numbers of both sexes from overwintering sites. No evidence
      was obtained for the production, in the spring, of any semiochemical by female
      weevils. 

PMID- 24302042
TI  - Inducible versus constitutive PI 227687 soybean resistance to mexican bean
      beetle,Epilachna varivestis.
AB  - Contrary to constitutive resistance, inducible resistance to Mexican bean beetle
      (MBB) (Epilachna varivestis) herbivory in PI 227687 soybean leaves was positively
      correlated with total phenolic content and temporally unique, increasedL
      phenylalanine ammonia-lyase (PAL) andL-tyrosine ammonia-lyase (TAL) activities.
      Initial expression of the induced resistance was localized at or near the site of
      herbivory. Systemic parameters of the induced resistance also were observed.
      Inducible MBB resistance in PI 227687 soybeans apparently involves increased
      phenylpropanoid metabolism. 

PMID- 24302043
TI  - Factors contributing to resistance of exotic maize populations to maize
      weevil,Sitophilus zeamais.
AB  - Factors contributing to resistance of maize to infestation by the corn
      weevilSitophilus zeamais were investigated in four populations of indigenous and
      improved maize from Belize. Resistance was related to the antifeedant properties
      of grain as well as sugar content and mechanical hardness. Grain extracts of all
      populations of maize significantly reduced insect feeding on treated artificial
      diets when compared to control diets. Consumption of treated diets was negatively
      correlated with phenolic content of the grain extract. An analysis by GC-MS
      indicated that ferulic acid andp-coumaric acid were the principal phenolics
      present in the extracts, and insect feeding was strongly deterred when pure
      substances were added to insect diets. Fluorescence associated with ferulic acid
      and related compounds in grain sections was located in the pericarp and aleurone
      layer and was especially intense in the most resistant grain variety. 

PMID- 24302044
TI  - Phenolic acetogenins secreted by rhododendron lace bug,Stephanitis rhododendri
      Horvath (Hemiptera: Tingidae).
AB  - Nymphs of the rhododendron lace bug produce from specialized setae a liquid
      secretion from which a number of related acetogenins have been identified. Two
      (2,6-dihydroxyphenyl)-1,3-diketones are the principal components and are
      accompanied by the corresponding chromones as well as by chromones bearing an
      additional phenolic oxygen. 

PMID- 24302045
TI  - Isoflavonoids as insect feeding deterrents and antifungal components from root
      ofLupinus angustifolius.
AB  - Crude extracts of the root of the resistant legume,Lupinus angustifolius, showed
      feeding deterrent activity toCostelytra zealandica andHeteronychus arator larvae.
      Nine 5-hydroxyisoflavones were isolated from an active fraction and their feeding
      deterrent activity and antifungal activity was measured. High feeding-deterrent
      activity was associated with high antifungal activity with some exceptions. 

PMID- 24302046
TI  - Isolation and identification of apolar metabolites of ingested 20-hydroxyecdysone
      in frass ofHeliothis virescens larvae.
AB  - A large amount of 20-hydroxyecdysone was orally administered to larvae of the
      tobacco budworm,Heliothis virescens, in order to investigate its detoxification
      mechanisms. Four major relatively nonpolar metabolites were isolated from their
      frass. These compounds were identified as the 22-linoleate, 22-palmitate, 22
      oleate, and 22-stearate of 20-hydroxyecdysone using various forms of
      spectroscopy, including NMR. This is the first report of this type of metabolite
      from an insect. 

PMID- 24302047
TI  - Variation in host fruit volatiles attractive to apple maggot fly,Rhagoletis
      pomonella.
AB  - We conducted a comparative study of volatiles produced by wholeCrataegus hawthorn
      fruit and four cultivars of apple (Royal Red Delicious, Red Astrachan, McIntosh,
      and Wealthy) and determined quantitative and qualitative changes of volatiles
      associated with fruit ripening. Within the approximate range of the GLC fraction
      known to elicit behavioral activity in the apple maggot fly,Rhagoletis pomonella
      (Walsh) (Diptera: Tephritidae), 52 esters were identified. 

PMID- 24302048
TI  - Quantitative and qualitative variation in male pheromones ofPhragmatobia
      fuliginosa andPyrrharctia isabella (Lepidoptera: Arctiidae).
AB  - The dihydropyrrolizine pheromones, hydroxydanaidal and danaidal, were identified
      from the scent organs of malePhragmatobia fuliginosa (L.) andPyrrharctia isabella
      (J.E. Smith). Qualitative and quantitative GLC analyses were conducted on ca. 80
      field-collected males of each species. The total pheromone titer was distributed
      bimodally in each species with most males having either a small amount (< 10 ng)
      of pheromone or a large amount (1-10 MUg inPyrrharctia and 0.3-3 MUg
      inPhragmatobia).Pyrrharctia males in the 1- to 10-MUg range had a predominance of
      hydroxydanaidal, with little if any danaidal. MostPhragmatobia males in the 0.3-
      to 3-MUg range had danaidal with little if any hydroxydanaidal. These compounds
      elicited a courtship response in sexually receptive females of both species. A
      bioassay based on this response was used to measure the thresholds of female
      response to these compounds.Pyrrharctia females were more sensitive to (R)-(-)
      hydroxydanaidal than to danaidal.Phragmatobia females were more sensitive to
      danaidal then to (R)-(-)-hydroxydanaidal. 

PMID- 24302049
TI  - Semiochemicals produced by western balsam bark beetle,Dryocoetes confusus Swaine
      (Coleoptera: Scolytidae).
AB  - The most prominent beetle-produced volatiles identified in the abdominal extracts
      of maleDryocoetes confusus Swaine after they had bored for 24 hr in logs of
      subalpine fir,Abies lasiocarpa (Hook.) Nutt. were:exo andendo-brevicomin,trans
      verbenol, verbenone, myrtenol,trans-pinocarveol,cis- andtrans-p-menthen-7-ol, 3
      caren-10-ol, and several monoterpenes and sesquiterpenes. Myrtenol was the only
      conspicuous compound in extracts from males that had been exposed toA.lasiocarpa
      resin volatiles for 24 hr. Laboratory bioassays indicated that both (-)- and (+)
      exo-brevicomin were attractive to femaleD. confusus, and that the (-) enantiomer
      did not inhibit response to its antipode. Results from field trapping experiments
      indicated that bothero-brevicomin and myrtenol are aggregation pheromones forD.
      confusus.exo-Brevicomin baits were effective in causing attack byD. confusus on
      baited and surrounding trees, suggesting that this pheromone may have utility in
      manipulating populations of the beetle. 

PMID- 24302050
TI  - Activity of volatile compounds in glandular trichomes ofLycopersicon species
      against two insect herbivores.
AB  - Several major chemicals in the glandular heads of type VI trichomes
      ofLycopersicon species were identified and quantified by gas chromatography and
      mass spectrometry. Two normal odd-chained ketones, 2-undecanone (47 ng) and 2
      tridecanone (146 ng), and one unknown sesquiterpene (5 ng), comprised
      approximately 95% of the contents of a gland ofL.hirsutum f.glabratum Mull. In a
      closely related plant,L.hirsutum Humb. & Bonpl. (LA 361), two unknown
      insecticidal sesquiterpenes accounted for 6% of the gland contents. Additionally,
      small amounts of one unknown monoterpene and another unknown sesquiterpene were
      found in type VI glands of a commercial tomato variety,L.esculentum Mill.
      Bioassays comparing the gland exudate (by direct contact) and isooctane extracts
      of glands to neonate larvae ofKeiferia lycopersicella (Walsingham) (Lepidoptera:
      Gelechiidae) andSpodoptera exigua (Hubner) (Lepidoptera: Noctuidae) indicated
      that: (1) 2-tridecanone and 2-undecanone were the major insecticidal compounds
      inL.hirsutum f.glabratum, (2) the two unknown sesquiterpenes inL.hirsutum were
      acutely toxic to both species, and (3) gland contents in the commercial tomato
      variety provided only a physical barrier toK.lycopersicella, and were not
      detrimental toS.exigua. In topical bioassay trials, synthetic mixtures of 2
      tridecanone and 2-undecanone (3 ?1) demonstrated potentiation. Concentrations of
      these chemicals decreased as trichomes aged. Quantities of insecticidal chemicals
      and density of type VI trichomes varied with plant age and location within
      plants. 

PMID- 24302051
TI  - Increased scent marking in male Mongolian gerbils by urinary polypeptides of
      female conspecifics.
AB  - Male Mongolian gerbils scent mark during a standardized openfield test on an
      individually different but more-or-less constant level in the absence of females.
      The presence of females in the same room but without direct contact to the males
      increases the marking frequencies of the males to an individually different
      higher level. A similar increase in marking frequency is obtained by application
      of female urine directly to the nostrils of the males, but not by male gerbil
      urine or female laboratory mouse urine. This indicates that substances present in
      female gerbil urine are responsible for the increase in male marking behavior.
      Using this bioassay, various fractions of female urine were tested for their
      influence on marking behavior. Our results to date show that the component
      increasing male scent-marking behavior is hydrophilic and nonvolatile and is
      contained in the nondialyzable, high-molecular-weight polypeptide fraction of
      female gerbil urine. 

PMID- 24302052
TI  - Synthesis and field bioassay of some analogs of sex pheromone of citrus
      mealybug,Planococcus citri (Risso).
AB  - A series of structural analogs of (s+)-cis-(1R)-3-isopropenyl-2,2
      dimethylcyclobutanemethanol acetate, sex pheromone of the citrus
      mealybug,Planococcus citri (Risso), was synthesized. The analogs were tested in a
      field bioassay in order to determine the structure-activity relationships of the
      pheromone. All changes in structure reduced the activity of the test compounds,
      to various degrees. The most active analog tested was the homolog (+)-cis-(1R)-3
      isopropenyl-2,2-dimethylcyclobutaneethanol acetate (IV), whose activity, at a
      higher dosage, was comparable to that of the pheromone. The alcohol (+)-cis-(1R)
      3-isopropenyl-2,2-dimethylcyclobutanemethanol was tested in mixtures with the
      pheromone and found to be neither an inhibitor nor a Synergist. The results show
      that all functional groups of the pheromone molecule are essential for optimal
      biological activity. 

PMID- 24302053
TI  - Responses of plant-parasitic nematodeMeloidogyne incognita to carbon dioxide
      determined by video camera-computer tracking.
AB  - A computer tracking system was used to quantify the responses of infective second
      stage juveniles of the plant-parasitic nematodeMeloidogyne incognita to carbon
      dioxide. A sudden increase in concentration caused an increase in the rate of
      locomotion and a decrease in the frequency of changes of direction. The threshold
      was about 0.01 % vol CO2/vol gas when the baseline concentration was very low and
      0.05% CO2 when the baseline concentration was 1% CO2. The latter value represents
      a relative change of 5%. Concentrations above 10% CO2 caused a general decrease
      in movement. In a second type of experiment, a constant concentration gradient of
      CO2 was established, and the net movement of the nematodes along the gradient was
      determined. At low concentrations, the threshold was about 0.02% CO2/cm. At
      higher concentrations, the threshold gradient was below 0.01% CO2/cm or a
      relative gradient of less than 1% change/cm. At all concentrations to which
      nematodes responded they were attracted. The degree of orientation was estimated
      to be approximately 10% under most conditions. The rate of migration under the
      most favorable conditions was about 0.7 cm/hr. Three possible functions of the
      response are discussed: attraction to roots, movement toward optimal depth in
      soil, and as a collimating stimulus. 

PMID- 24302054
TI  - Role of benzoxazinones in allelopathy by rye (Secale cereale L.).
AB  - Two phytotoxic compounds [2,4-dihydroxy-1,4(2H)-benzoxazin-3-one (DIBOA) and
      2(3H)-benzoxazolinone (BOA)] were previously isolated and identified in 35-day
      old greenhouse-grown rye shoot tissue. Both compounds were also detected by TLC
      in greenhouse-grown root and fieldgrown shoot tissue. The concentration of DIBOA
      varied in the tissues, with the greatest quantity detected in greenhouse-grown
      shoots. DIBOA and BOA were compared with beta-phenyllactic acid (PLA) and beta
      hydroxybutyric acid (HBA) for activity on seed germination and seedling growth
      and were consistently more toxic than either compound. Dicot species tested,
      including lettuce (Lactuca sativa L.), tomato (Lycopersicon esculentum Mill.),
      and redroot pigweed (Amaranthus retroflexus L.), were 30% more sensitive than the
      monocots tested. Of the two benzoxazinone compounds, DIBOA was most toxic to
      seedling growth. DIBOA and BOA reduced chlorophyll production inChlamydomonas
      rheinhardtii Dangeard, by 50% at 7.5 * 10(-5) M and 1.0 * 10(-3) M, respectively.
      Both DIBOA and BOA inhibited emergence of barnyardgrass (Echinochloa crusgalli L.
      Beauv.), cress (Lepidium sativum L.), and lettuce when applied to soil,
      indicating their potential for allelopathic activity. 

PMID- 24302055
TI  - Identification of sex pheromone of calendula plume mothPlatyptilia williamsii.
AB  - The sex pheromone of the calendula plume moth,Platyptilia williamsii was
      identified as (Z)-11-hexadecenal (Z11-16?Aid). Extracts of female sex pheromone
      glands contained several compounds when analyzed by capillary and packed-column
      GLC. However, airborne collections of volatiles from glands contained only one of
      these compounds, having the same retention time asZ11-16?Ald. GC-MS and
      microozonolysis analyses of the natural product were consistent with those of
      syntheticZ11-16?Ald. In a flight tunnel, males oriented upwind and touched
      sources ofZ11-16?Ald and gland extract with equal frequency. Field tests of
      syntheticZ11-16?Ald already have shown it to be a potent sex attractant for males
      of this species. This study further supports the hypothesis thatP. williamsii and
      a sympatric species,Platyptilia carduidactyla, are not reproductively isolated by
      chemical differences in the composition of the sex pheromone, but rather by
      temporal differences in sexual activities. 

PMID- 24302056
TI  - Lack of chemical factors in host-plant resistance of alfalfa towards alfalfa
      weevil: Ovicidal activity of some coumarin derivatives.
AB  - A resistant line of alfalfa was studied in an attempt to identify possible
      chemical factors responsible for alfalfa weevil (Hypera brunneipennis)
      resistance. Bioassays were developed to measure ovicidal, larval development,
      pupation, and adult development rates. Serial alfalfa extracts of a weevil
      resistant line showed no effect in the bioassays when compared to those of a
      weevil-susceptible line. It was concluded that resistance substances are not
      present but that resistant lines are simply more tolerant to weevil attack.
      Alfalfa constitutents and synthetic analogs were also screened in the egg hatch
      bioassay. Among these were a series of 3-acyl-4-hydroxycoumarins. 3-Acyl-4
      hydroxycoumarins with short-chain acyl groups showed good ovicidal rates, but
      activity decreased with increasing length of the acyl group. 

PMID- 24302057
TI  - Feeding deterrency of some 4-hydroxycoumarins and related compounds: Relationship
      to host-plant resistance of alfalfa towards pea aphid (Acyrthosiphon pisum).
AB  - A series of 3-acyl-4-hydroxycoumarins, structurally related to dicoumarol, as
      well as several alfalfa constituents including coumestrol were tested for their
      feeding deterrency towards the pea aphid. Feeding deterrency of the 3-acyl-4
      hydroxycoumarins decreased as the size of the 3-acyl group increased. 

PMID- 24302058
TI  - Attraction of sphingid moths (Lepidoptera: Sphingidae) to 10,12-hexadecadienyl
      aldehydes and acetates: Evidence of pheromone components.
AB  - A field survey of 10,12-hexadecadienyl alcohols, acetates, and aldehydes showed
      attraction to a wide range of sphingid moths. Data are presented showing the
      attraction ofSmerinthus jamaicensis, Smerinthus cerisyi, Pachysphinx modesta,
      Hemaris diffinis, andProserpinus flavofasciata to these compounds. Mass spectral,
      EAG, and EAD data show evidence for the presence of these dienes in female
      extracts ofS. cerisyi, Hyles gallii, andSphinx drupiferarum. 

PMID- 24302059
TI  - Technique for visualization of epidermal glandular structures in plants.
AB  - The distribution of microscopic glandular structures (hairs, capsules, nodules)
      on a leaf or other plant part can be recorded visually by pressing the plant part
      against an indicator surface (filter paper, thin-layer chromatography plate)
      soaked in Tollens' reagent. The glandular sites are revealed instantly on the
      test surface as dark spots. 

PMID- 24302060
TI  - Interaction of nuclear polyhedrosis virus with catechols: Potential
      incompatibility for host-plant resistance against noctuid larvae.
AB  - Two major orthodihydroxy phenolics ofLycopersicon esculentum, rutin and
      chlorogenic acid, have previously been identified as potential sources of host
      plant resistance against the tomato fruitwormHeliothis zea. We report here the
      possible incompatibility of these chemically based resistance factors with viral
      control ofH, zea. We have found that both rutin and chlorogenic acid
      significantly inhibited the infectivity of nuclear polyhedrosis viruses.
      Chlorogenic acid, when added to tissue culture medium containing TN-368 ovarian
      cells, inhibited the infectivity of a multiply embedded virus (AcMNPV) by over
      86%. Rutin or chlorogenic acid, when fed toH. zea, inhibited the infectivity of a
      singly embedded nuclear polyhedrosis virus (HzSNPV), with the greatest degree of
      inhibition occurring at low doses of viral inoculum. Additionally, the ingestion
      of these phytochemicals significantly prolonged the survival time of virally
      infectedH. zea larvae. These results suggest that the effectiveness of nuclear
      polyhedrosis viruses in controllingH. zea populations may be adversely affected
      by varieties ofL. esculentum with significant levels (eg. 3.5 MUmol/g wet weight)
      of rutin or chlorogenic acid. 

PMID- 24302061
TI  - Semiochemical attractants ofDiabrotica undecimpunctata howardi barber, southern
      corn rootworm, andDiabrotica virgifera virgifera leconte, the western corn
      rootworm (Coleoptera: Chrysomelidae).
AB  - During the summers of 1984 and 1985, a variety of structurally related benzenoid
      compounds was evaluated in sweet corn plots as attractants for adult southern
      corn rootworms (SCR), western com rootworms (WCR), and northern corn rootworms
      (NCR). Field response to the volatiles was measured by beetle counts on baited
      cylindrical sticky traps placed inside the corn plots at a height of l m above
      ground level. SCR adults were attracted late in the season (last week of August
      through September, 1984 and 1985) to numerous aromatic compounds, including
      phenylacetaldehyde, benzyl acetone, phenethyl alcohol, phenyl acetate, indole,
      veratrole, methyl eugenol, methyl isoeugenol, eugenol, and isoeugenol. Although
      many compounds attracted SCR adults late in the season, only veratrole,
      phenylacetaldehyde, and chavicol were significantly active in early and middle
      August 1985. WCR adults were attracted to a different group of compounds, namely
      estragole,trans-anethole, and indole. Estragole (4-methoxy-1-allylbenzene) was an
      effective WCR attractant from corn tasseling in early August 1985, until the end
      of the trapping period in late September and early October 1985. Indole andtrans
      anethole (4-methoxy-1-propenylbenzene) were less effective attractants than
      estragole and were most active at the beginning and/or end of the corn season.
      Traps baited with 100 mg of estragole caught an average of 20 times more WCR
      adults than unbaited control traps, and the females outnumbered the males in the
      baited traps. Estragole dosage tests were conducted in three sweet corn plots on
      different dates in 1985 and the minimum effective dose ranged between 5 and 30
      mg/trap. Field tests with structural analogs revealed the importance of the site
      of unsaturation in the allylic side chain of estragole and the effect of
      different ring substituents on WCR response. The phenylpropanoids, eugenol and
      isoeugenol, significantly attracted NCR adults, even though these beetles were in
      low abundance in the test corn plots. Field tests indicate there is no cross
      species response by WCR and NCR adults to their related phenylpropanoid
      attractants. However, in late August, SCR adults do respond to some WCR and NCR
      attractants (indole and several eugenol analogs). Electroantennographic analysis
      of SCR males revealed they can perceive peripherally a wide range of benzenoid
      compounds. 

PMID- 24302062
TI  - Near-infrared photocatalysts of BiVO4/CaF2:Er3+, Tm3+, Yb3+ with enhanced
      upconversion properties.
AB  - Upconversion photocatalysts have the potential to absorb the near-infrared (NIR)
      light in solar energy and improve the photocatalytic performance. A hierarchical
      upconversion photocatalyst of BiVO4 (BVO)/CaF2:Er(3+), Tm(3+), Yb(3+) (CF)
      combined with the narrow-band semiconductor of BVO and the luminescence agent of
      CF to enhance upconversion properties was synthesized via the hydrothermal
      method. The CF particles were deposited homogeneously on the surface of the
      BVO/CF composite with regular dendritic structure, which led to efficient
      upconversion emissions. The upconversion emission intensity of the BVO/CF
      composite was 8 times higher than that of pure CF, through tailoring the crystal
      symmetry of lanthanide ions by Bi(3+) ions. The upconverted ultraviolet (361 and
      379 nm), violet (408 nm), and blue (485 nm) light was able to excite BVO for
      photocatalysis in BVO/CF under NIR irradiation, which improved the degradation
      rate of methyl orange (MO).

PMID- 24302063
TI  - Densification of a continuous random network model of amorphous SiO2 glass.
AB  - We have investigated the mechanism of densification of a nearly perfect
      continuous random network (CRN) model of amorphous SiO2 (a-SiO2) glass with 1296
      atoms and periodic boundary conditions. The model has no under- or over
      coordinated atoms and small bond length and bond angle distributions. This near
      perfect model is systematically densified up to a pressure of 80 GPa using ab
      initio constant-pressure technique. By assessing a full spectrum of properties
      including atomic structure, bonding characteristics, effective charges, bond
      order values, electron density of states, localization of wave functions, elastic
      and mechanical properties, and interband optical absorption at each pressure, we
      reveal the pertinent details on the structural, mechanical and optical
      characteristics of the glass model under pressure. They all confirm the central
      theme that amorphous to amorphous phase transformation (AAPT) from a low-density
      state to a high-density state is at a pressure between 20 and 35 GPa in this
      nearly ideal a-SiO2 network. This pressure range represents an upper limit for
      such a transition in vitreous silica. The phase transformation roots from the
      change of Si-O bonding from a mixture of ionic and covalent nature at low
      pressure to a highly covalent bonding under high pressure. In addition, the
      calculated theoretical refractive index of the glass model as a function of the
      pressure is reported for the first time and in good agreement with the available
      experimental data. 

PMID- 24302064
TI  - Some contemporary addictions.

PMID- 24302065
TI  - Context of practice, practice of context: A psychotherapeutic meditation.
AB  - Intended as an essay on the perennial topic of the relation between theory and
      practice, which will not be all theory and no practice, this paper draws on
      contemporary philosphy of science and clinical theory to catalyze the reader's
      own further reflections on the topic by suggesting that the meanings of theories
      and practices are context-dependent, and so the question can never be answered in
      the abstract, and that the separation of theory and practice is something we can
      do only in theory, never in practice. 

PMID- 24302066
TI  - Alcoholism: A conflict of models.
AB  - Adherents to the traditional model of alcoholism explain alcoholic behavior as a
      consequence of alcoholism. Alcoholism is identified as an unseen, unmeasured
      entity inherent in alcoholics. This concept parallels the thinking of Copernicus,
      Kepler, Galileo, and Newton, who believed in an unseen, unmeasurable creator
      behind the physical world. These traditional approaches contrast with the
      emergent model of alcoholism and twentieth-century scientific thought. Emergent
      scientific model adherents explain alcoholic behavior without resort to unseen
      factors. Since the traditional and emergent scientific models begin with
      different assumptions, model adherents experience communication difficulties.
      Future developments with determine which model will dominate the field of alcohol
      studies and treatment. 

PMID- 24302067
TI  - Re-exploring anger: Its dynamics and treatment.
AB  - The conventional wisdom in counseling circles has been that persons filled with
      anger basically need catharsis. Recent thinking challenges this assumption. New
      questions arise, such as why is the anger necessary, and whose responsibility is
      it to deal with it? Some dynamics are discussed, and two case illustrations are
      presented. 

PMID- 24302068
TI  - The meaning of prayer: A Christian physician's experience.
AB  - Christians in health care need a habit of prayer that allows them to express to
      God the full range of their reactions to daily experience. All of life can become
      the occasion for prayer when understood as communion or conversation. After brief
      commentary on this view of prayer, actual prayers are shared, demonstrating one
      Christian physician's attempts to "pray without ceasing". 

PMID- 24302069
TI  - Encounter with death: The thought of Robert Jay Lifton.
AB  - Robert Jay Lifton begins his work in the psychosocial framework that he takes
      over from Erik Erikson. Lifton's thought is based upon a central paradigm-"death
      and the continuity of life." Lifton makes important contributions with his five
      modes of symbolic immortality and with his investigation of the psychological
      themes in survivors. The origins and limits of Lifton's thought are critically
      examined. 

PMID- 24302070
TI  - The initiation ritual as a model for oncology counseling.
AB  - This article examines the use of the initiation ritual of primitive people,
      described in the works of Mircea Eliade, as a model for counseling cancer
      patients, giving both meaning and structure to the interactions between patient
      and counselor. Within this model the patient's encounter with death, whether
      feared or actualized, can be used as impetus toward personal growth, whatever the
      stage of the person's disease process. Case examples are given to illustrate how
      the model can be used in practice. Comparison is also made between stages and
      components of the initiation ritual and other techniques used to alter a person's
      consciousness. 

PMID- 24302071
TI  - Discovering what it all means.
AB  - This article deals with appropriate communication and interpersonal skills that
      nurses may use in order to support patients who are experiencing self-concept
      changes related to their health problems. Three areas of patient need related to
      self-concept are explored. The stages of adaptation to loss and the crucial task
      of grief work are reviewed, and nursing interventions designed to strengthen the
      self-concept and support patients as they adapt to loss are suggested. Sensitive
      communication, although a "low-visibility" nursing skill, is cited as critical in
      assisting the patient to achieve an optimum level of wellness. 

PMID- 24302072
TI  - RAFT polymerized nanoparticles: influences of shell and core chemistries on
      performance for electrokinetic chromatography.
AB  - The performance and solvation characteristics of two novel latex nanoparticle
      (NP) pseudo-stationary phases (PSPs) for EKC are determined and compared to those
      of previously reported micellar, polymeric, and NP materials. The new NPs have
      shells composed of strongly acidic poly(AMPS) as opposed to the poly(acrylic
      acid) shell of the prior NP, and have varied hydrophobic core chemistry of either
      poly(butyl acrylate) or poly(ethyl acrylate). The NPs poly(AMPS) shell shows only
      minor changes in mobility and selectivity between pH 4.9 and 9.4, allowing
      adjustment of pH to influence and optimize separation performance. All of the NP
      phases have significantly different solvation characteristics and selectivity
      relative to SDS micelles. The selectivity and solvent character are similar for
      NPs with poly(butyl acrylate) cores and different shells, but vary significantly
      between NPs with poly(butyl acrylate) versus poly(ethyl acrylate) cores. NPs with
      poly(butyl acrylate) cores are among the least cohesive PSPs reported to date,
      while the NP with poly(ethyl acrylate) core is among the most cohesive. The
      results demonstrate that PSPs with unique selectivity can be generated by
      altering the chemistry of the hydrophobic core. 

PMID- 24302073
TI  - Novel beta-ketoiminato complexes of zirconium: synthesis, characterization and
      evaluation for solution based processing of ZrO2 thin films.
AB  - Treatment of tetrakis(diethylamido)zirconium(IV); [Zr(NEt2)4] with a series of
      beta-ketoimines ({[RHN]C(CH3)=C(H)C(CH3)=O} where R is a functionalized side
      chain; 4-(2-methoxyethylamino)pent-3-en-2-one, Hmeap; 4-(3
      methoxypropylamino)pent-3-en-2-one, Hmpap; 4-(2-(dimethylamino)ethylamino)pent-3
      en-2-one, Hdeap; 4-(3-(dimethylamino)propylamino)pent-3-en-2-one, Hdpap) leads to
      an amine substitution reaction that yielded novel monomeric heteroleptic mixed
      amido-ketoiminato complexes of the type bis(4-(2-methoxyethylamino)pent-3-en-2
      onato)bis(diethylamido)zirconium(IV) (1), bis(4-(3-methoxypropylamino)pent-3-en-2
      onato)bis(diethylamido)zirconium(IV) (2), and bis(4-(3
      (dimethylamino)propylamino)pent-3-en-2-onato)bis(diethylamido)zirconium(IV) (3),
      and eight-coordinated homoleptic complexes tetrakis(4-(2-methoxyethylamino)pent-3
      en-2-onato)zirconium(IV) (4) and tetrakis(4-(2-(dimethylamino)ethylamino)pent-3
      en-2-onato)zirconium(IV) (5), depending on the ratio of the ligand to zirconium.
      Adopting a similar strategy with zirconium alkoxide, namely
      [Zr(O(i)Pr)4.(i)PrOH], with beta-ketoimine Hmeap, leads to the formation of a
      dimer, bis(MU2-isopropoxo)bis(4-(2-methoxyethylamino)pent-3-en-2
      onato)tetrakis(isopropoxo)dizirconium(IV) (6). The newly synthesised complexes
      were characterized by NMR spectroscopy, mass spectrometry, single crystal X-ray
      diffraction, elemental analysis and thermal analysis. The low decomposition
      temperature facilitated by the stepwise elimination of the ketominate ligand from
      the complex and the stability of the complexes obtained in air as well as in
      solution makes them highly suitable for solution based processing of ZrO2 thin
      films, which is demonstrated using compound 5 on Si(100) substrates. High quality
      ZrO2 films were obtained and were investigated for their structure, morphology,
      composition and optical properties. Low temperature crystallisation of ZrO2 is
      achieved by a simple chemical deposition process using the new class of Zr
      precursors and the films exhibit an optical transmittance above 90%.

PMID- 24302074
TI  - Real-time influenza forecasts during the 2012-2013 season.
AB  - Recently, we developed a seasonal influenza prediction system that uses an
      advanced data assimilation technique and real-time estimates of influenza
      incidence to optimize and initialize a population-based mathematical model of
      influenza transmission dynamics. This system was used to generate and evaluate
      retrospective forecasts of influenza peak timing in New York City. Here we
      present weekly forecasts of seasonal influenza developed and run in real time for
      108 cities in the USA during the recent 2012-2013 season. Reliable ensemble
      forecasts of influenza outbreak peak timing with leads of up to 9 weeks were
      produced. Forecast accuracy increased as the season progressed, and the forecasts
      significantly outperformed alternate, analogue prediction methods. By week 52,
      prior to peak for the majority of cities, 63% of all ensemble forecasts were
      accurate. To our knowledge, this is the first time predictions of seasonal
      influenza have been made in real time and with demonstrated accuracy. 

PMID- 24302076
TI  - Gender differentiation in indirect self-destructiveness and suicide attempt
      methods (gender, indirect self-destructiveness, and suicide attempts).
AB  - The objective of this study is to examine the gender (sex) differentiation of
      indirect self-destructiveness and its manifestations as well as its relationships
      with suicide attempt methods in females and males. The study was conducted among
      147 persons (114 females, 33 males) who attempted suicide. The research
      instrument was the polish version of the Chronic Self-Destructiveness Scale
      including Transgression and Risk, Poor Health Maintenance, Personal and Social
      Neglects, Lack of Planfulness, and Helplessness and Passiveness in the face of
      problems. Differences testing and correlation analyses were applied. Females
      scored higher on poor health maintenance and males scored significantly higher on
      personal and social neglects, lack of planfulness, and helplessness. Noteworthy
      is that the intensity of indirect self-destructiveness in females reached the
      same magnitude as in males. A number of statistically significant correlations
      were found between indirect self-destructiveness, or its manifestations, and the
      methods of suicide attempt in the two groups. Among these categories, the highest
      contribution was of helplessness and passiveness (both of groups), poor health
      maintenance (males), and personal and social neglects (females). Results of this
      study can be useful in the therapeutic efforts and prevention of not only
      indirectly self-destructive behaviours but also possible suicide attempts. Both
      preventive and therapeutic activities can take into account the specificity of
      those phenomena resulting from one's sex/gender. It is important to adapt
      preventive and therapeutic measures to psychological (personal) features that
      arise from an individual's sex/gender. 

PMID- 24302079
TI  - The tiff: Florence Carlyle.

PMID- 24302080
TI  - The new 2015 MCAT: testing competencies.

PMID- 24302081
TI  - The evolution of the United States Medical Licensing Examination (USMLE):
      enhancing assessment of practice-related competencies.

PMID- 24302082
TI  - The oral patient presentation in the era of night float admissions: credit and
      critique.

PMID- 24302083
TI  - Refocusing medical education in the EMR era.

PMID- 24302084
TI  - A piece of my mind. Unintended consequences.

PMID- 24302085
TI  - Will changes in the MCAT and USMLE ensure that future physicians have what it
      takes?

PMID- 24302086
TI  - Does improving handoffs reduce medical error rates?

PMID- 24302087
TI  - Improving communication with patients: learning by doing.

PMID- 24302088
TI  - Containing multitudes: medical education 2013.

PMID- 24302089
TI  - Rates of medical errors and preventable adverse events among hospitalized
      children following implementation of a resident handoff bundle.
AB  - IMPORTANCE: Handoff miscommunications are a leading cause of medical errors.
      Studies comprehensively assessing handoff improvement programs are lacking.
      OBJECTIVE: To determine whether introduction of a multifaceted handoff program
      was associated with reduced rates of medical errors and preventable adverse
      events, fewer omissions of key data in written handoffs, improved verbal
      handoffs, and changes in resident-physician workflow. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective intervention study of 1255 patient admissions (642
      before and 613 after the intervention) involving 84 resident physicians (42
      before and 42 after the intervention) from July-September 2009 and November 2009
      January 2010 on 2 inpatient units at Boston Children's Hospital. INTERVENTIONS:
      Resident handoff bundle, consisting of standardized communication and handoff
      training, a verbal mnemonic, and a new team handoff structure. On one unit, a
      computerized handoff tool linked to the electronic medical record was introduced.
      MAIN OUTCOMES AND MEASURES: The primary outcomes were the rates of medical errors
      and preventable adverse events measured by daily systematic surveillance. The
      secondary outcomes were omissions in the printed handoff document and resident
      time-motion activity. RESULTS: Medical errors decreased from 33.8 per 100
      admissions (95% CI, 27.3-40.3) to 18.3 per 100 admissions (95% CI, 14.7-21.9; P <
      .001), and preventable adverse events decreased from 3.3 per 100 admissions (95%
      CI, 1.7-4.8) to 1.5 (95% CI, 0.51-2.4) per 100 admissions (P = .04) following the
      intervention. There were fewer omissions of key handoff elements on printed
      handoff documents, especially on the unit that received the computerized handoff
      tool (significant reductions of omissions in 11 of 14 categories with
      computerized tool; significant reductions in 2 of 14 categories without
      computerized tool). Physicians spent a greater percentage of time in a 24-hour
      period at the patient bedside after the intervention (8.3%; 95% CI 7.1%-9.8%) vs
      10.6% (95% CI, 9.2%-12.2%; P = .03). The average duration of verbal handoffs per
      patient did not change. Verbal handoffs were more likely to occur in a quiet
      location (33.3%; 95% CI, 14.5%-52.2% vs 67.9%; 95% CI, 50.6%-85.2%; P = .03) and
      private location (50.0%; 95% CI, 30%-70% vs 85.7%; 95% CI, 72.8%-98.7%; P = .007)
      after the intervention. CONCLUSIONS AND RELEVANCE: Implementation of a handoff
      bundle was associated with a significant reduction in medical errors and
      preventable adverse events among hospitalized children. Improvements in verbal
      and written handoff processes occurred, and resident workflow did not change
      adversely.

PMID- 24302091
TI  - Student attendance and academic performance in undergraduate
      obstetrics/gynecology clinical rotations.
AB  - IMPORTANCE: Student attendance is thought to be an important factor in the
      academic performance of medical students, in addition to having important
      regulatory, policy, and financial implications for medical educators. However,
      this relationship has not been well evaluated within clinical learning
      environments. OBJECTIVE: To evaluate the relationship between student attendance
      and academic performance in a medical student obstetrics/gynecology clinical
      rotation. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of
      student attendance at clinical and tutorial-based activities during a full
      academic year (September 2011 to June 2012) within a publicly funded university
      teaching hospital in Dublin, Ireland. Students were expected to attend 64
      activities (26 clinical activities and 38 tutorial-based activities) but
      attendance was not mandatory. All 147 fourth-year medical students who completed
      an 8-week obstetrics/gynecology rotation were included. EXPOSURES: Student
      attendance at clinical and tutorial-based activities, recorded using a paper
      based logbook. MAIN OUTCOMES AND MEASURES: The overall examination score (out of
      a possible 200 points) was obtained using an 11-station objective structured
      clinical examination (40 points), an end-of-year written examination comprising
      50 multiple-choice questions (40 points) and 6 short-answer questions (40
      points), and an end-of-year long-case clinical/oral examination (80 points).
      Students were required to have an overall score of 100 points (50%) and a minimum
      of 40 points in the long-case clinical/oral examination (50%) to pass. RESULTS:
      The mean attendance rate was 89% (range, 39%-100% [SD, 11%], n = 57/64
      activities). Male students (84% attendance, P = .001) and students who failed an
      end-of-year examination previously (84% attendance, P = .04) had significantly
      lower rates. There was a positive correlation between attendance and overall
      examination score (r = 0.59 [95% CI, 0.44-0.70]; P < .001). Both clinical
      attendance (r = 0.50 [95% CI, 0.32-0.64]; P < .001) and tutorial-based attendance
      (r = 0.57 [95% CI, 0.40-0.70]; P < .001) were positively correlated with overall
      examination score. The associations persisted after controlling for confounding
      factors of student sex, age, country of origin, previous failure in an end-of
      year examination, and the timing of the rotation during the academic year.
      Distinction grades (overall score of >=60%) were present only among students with
      attendance rates of 80% or higher. The odds of a distinction grade increased with
      each 10% increase in attendance (adjusted odds ratio, 5.52; 95% CI, 2.17-14.00).
      The majority of failure grades (6/10 students; 60%) occurred in students with
      attendance rates lower than 80%. The adjusted odds ratio for failure with
      attendance rates of 80% or higher was 0.11 (95% CI, 0.02-0.72). CONCLUSIONS AND
      RELEVANCE: Among fourth-year medical students completing an 8-week
      obstetrics/gynecology clinical rotation, attendance at clinical and tutorial
      based activities was positively correlated with overall examination scores.
      Further research is needed to understand whether the relationship is causal, and
      whether improving attendance rates can improve academic performance.

PMID- 24302090
TI  - Effect of communication skills training for residents and nurse practitioners on
      quality of communication with patients with serious illness: a randomized trial.
AB  - IMPORTANCE: Communication about end-of-life care is a core clinical skill.
      Simulation-based training improves skill acquisition, but effects on patient
      reported outcomes are unknown. OBJECTIVE: To assess the effects of a
      communication skills intervention for internal medicine and nurse practitioner
      trainees on patient- and family-reported outcomes. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized trial conducted with 391 internal medicine and 81 nurse
      practitioner trainees between 2007 and 2013 at the University of Washington and
      Medical University of South Carolina. INTERVENTION: Participants were randomized
      to an 8-session, simulation-based, communication skills intervention (N = 232) or
      usual education (N = 240). MAIN OUTCOMES AND MEASURES: Primary outcome was
      patient-reported quality of communication (QOC; mean rating of 17 items rated
      from 0-10, with 0 = poor and 10 = perfect). Secondary outcomes were patient
      reported quality of end-of-life care (QEOLC; mean rating of 26 items rated from 0
      10) and depressive symptoms (assessed using the 8-item Personal Health
      Questionnaire [PHQ-8]; range, 0-24, higher scores worse) and family-reported QOC
      and QEOLC. Analyses were clustered by trainee. RESULTS: There were 1866 patient
      ratings (44% response) and 936 family ratings (68% response). The intervention
      was not associated with significant changes in QOC or QEOLC. Mean values for
      postintervention patient QOC and QEOLC were 6.5 (95% CI, 6.2 to 6.8) and 8.3 (95%
      CI, 8.1 to 8.5) respectively, compared with 6.3 (95% CI, 6.2 to 6.5) and 8.3 (95%
      CI, 8.1 to 8.4) for control conditions. After adjustment, comparing intervention
      with control, there was no significant difference in the QOC score for patients
      (difference, 0.4 points [95% CI, -0.1 to 0.9]; P = .15) or families (difference,
      0.1 [95% CI, -0.8 to 1.0]; P = .81). There was no significant difference in QEOLC
      score for patients (difference, 0.3 points [95% CI, -0.3 to 0.8]; P = .34) or
      families (difference, 0.1 [95% CI, -0.7 to 0.8]; P = .88). The intervention was
      associated with significantly increased depression scores among patients of
      postintervention trainees (mean score, 10.0 [95% CI, 9.1 to 10.8], compared with
      8.8 [95% CI, 8.4 to 9.2]) for control conditions; adjusted model showed an
      intervention effect of 2.2 (95% CI, 0.6 to 3.8; P = .006). CONCLUSIONS AND
      RELEVANCE: Among internal medicine and nurse practitioner trainees, simulation
      based communication training compared with usual education did not improve
      quality of communication about end-of-life care or quality of end-of-life care
      but was associated with a small increase in patients' depressive symptoms. These
      findings raise questions about skills transfer from simulation training to actual
      patient care and the adequacy of communication skills assessment. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00687349.

PMID- 24302092
TI  - Substance use disorder among anesthesiology residents, 1975-2009.
AB  - IMPORTANCE: Substance use disorder (SUD) among anesthesiologists and other
      physicians poses serious risks to both physicians and patients. Formulation of
      policy and individual treatment plans is hampered by lack of data regarding the
      epidemiology and outcomes of physician SUD. OBJECTIVE: To describe the incidence
      and outcomes of SUD among anesthesiology residents. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective cohort study of physicians who began training in
      United States anesthesiology residency programs from July 1, 1975, to July 1,
      2009, including 44,612 residents contributing 177,848 resident-years to analysis.
      Follow-up for incidence and relapse was to the end of training and December 31,
      2010, respectively. MAIN OUTCOMES AND MEASURES: Cases of SUD (including initial
      SUD episode and any relapse, vital status and cause of death, and professional
      consequences of SUD) ascertained through training records of the American Board
      of Anesthesiology, including information from the Disciplinary Action
      Notification Service of the Federation of State Medical Boards and cause of death
      information from the National Death Index. RESULTS: Of the residents, 384 had
      evidence of SUD during training, with an overall incidence of 2.16 (95% CI, 1.95
      2.39) per 1000 resident-years (2.68 [95% CI, 2.41-2.98] men and 0.65 [95% CI,
      0.44-0.93] women per 1000 resident-years). During the study period, an initial
      rate increase was followed by a period of lower rates in 1996-2002, but the
      highest incidence has occurred since 2003 (2.87 [95% CI, 2.42-3.39] per 1000
      resident-years). The most common substance category was intravenous opioids,
      followed by alcohol, marijuana or cocaine, anesthetics/hypnotics, and oral
      opioids. Twenty-eight individuals (7.3%; 95% CI, 4.9%-10.4%) died during the
      training period; all deaths were related to SUD. The Kaplan-Meier estimate of the
      cumulative proportion of survivors experiencing at least 1 relapse by 30 years
      after the initial episode (based on a median follow-up of 8.9 years
      [interquartile range, 5.0-18.8 years]) was 43% (95% CI, 34%-51%). Rates of
      relapse and death did not depend on the category of substance used. Relapse rates
      did not change over the study period. CONCLUSIONS AND RELEVANCE: Among
      anesthesiology residents entering primary training from 1975 to 2009, 0.86% had
      evidence of SUD during training. Risk of relapse over the follow-up period was
      high, indicating persistence of risk after training.

PMID- 24302093
TI  - Minority Faculty Development Programs and Underrepresented Minority Faculty
      Representation at US Medical Schools.
AB  - IMPORTANCE: Diversity initiatives have increased at US medical schools to address
      underrepresentation of minority faculty. OBJECTIVE: To assess associations
      between minority faculty development programs at US medical schools and
      underrepresented minority faculty representation, recruitment, and promotion.
      DESIGN: Secondary analysis of the Association of American Medical Colleges
      Faculty Roster, a database of US medical school faculty. PARTICIPANTS: Full-time
      faculty at schools located in the 50 US states or District of Columbia and
      reporting data from 2000-2010. EXPOSURE: Availability of school-wide programs
      targeted to underrepresented minority faculty in 2010. MAIN OUTCOMES AND
      MEASURES: Percentage of underrepresented minority faculty, defined as self
      reported black, Hispanic, Native American, Alaskan Native, Native Hawaiian, or
      Pacific Islander faculty. Percentage of underrepresented minority faculty was
      computed by school and year for all faculty, newly appointed faculty, and newly
      promoted faculty. Panel-level analyses that accounted for faculty clustering
      within schools were conducted and adjusted for faculty- and school-level
      variables. RESULTS: Across all schools, the percentage of underrepresented
      minority faculty increased from 6.8% (95% CI, 6.7%-7.0%) in 2000 to 8.0% (95% CI,
      7.8%-8.2%) in 2010. Of 124 eligible schools, 36 (29%) were identified with a
      minority faculty development program in 2010. Minority faculty development
      programs were heterogeneous in composition, number of components, and duration.
      Schools with minority faculty development programs had a similar increase in
      percentage of underrepresented minority faculty as schools without minority
      faculty development programs (6.5%-7.4% vs 7.0%-8.3%; odds ratio [OR], 0.91 [95%
      CI, 0.72-1.13]). After adjustment for faculty and school characteristics,
      minority faculty development programs were not associated with greater
      representation of minority faculty (adjusted OR, 0.99 [95% CI, 0.81-1.22]),
      recruitment (adjusted OR, 0.97 [95% CI, 0.83-1.15]), or promotion (adjusted OR,
      1.08 [95% CI, 0.91-1.30]). In subgroup analyses, schools with programs of greater
      intensity (present for >=5 years and with more components) were associated with
      greater increases in underrepresented minority representation than schools with
      minority faculty development programs of less intensity. CONCLUSIONS AND
      RELEVANCE: The percentage of underrepresented minority faculty increased modestly
      from 2000 to 2010 at US medical schools. The presence of a minority faculty
      development program targeted to underrepresented minority faculty was not
      associated with greater underrepresented minority faculty representation,
      recruitment, or promotion. Minority faculty development programs that were of
      greater intensity were associated with greater increases in underrepresented
      minority faculty representation.

PMID- 24302094
TI  - Publication of results of abstracts presented at medical education conferences.

PMID- 24302095
TI  - Clinical performance of medical students with protected disabilities.

PMID- 24302096
TI  - Soy protein and recurrence of prostate cancer.

PMID- 24302097
TI  - Soy protein and recurrence of prostate cancer--reply.

PMID- 24302098
TI  - Androgen deprivation therapy and acute kidney injury.

PMID- 24302099
TI  - Androgen deprivation therapy and acute kidney injury--reply.

PMID- 24302101
TI  - Public opinion and medical education.

PMID- 24302102
TI  - Medical schools in the United States, 2012-2013.

PMID- 24302103
TI  - Graduate medical education, 2012-2013.

PMID- 24302104
TI  - JAMA patient page. Patient handoffs in teaching hospitals.

PMID- 24302105
TI  - Tissue origins, cell lineages and patterns of cell division in the developing
      dermal system of the frut of Vitis vinifera L.
AB  - Cell division during development of the dermal system of fruit of the grape cv.
      Gordo is confined to the first growth period. The epidermis is conserved with
      anticlinal proliferative cell divisions providing for increase in cell number.
      The hypodermis is the layer of origin of the collenchymatous dermal system. Six
      or seven layers are differentiated by periclinal cell divisions early in the
      first growth period, and later increase in size is obtained by proliferative
      anticlinal cell divisions. These observations are related to developmental and
      genetic control of fruit shape and volume. 

PMID- 24302106
TI  - Toward a biophysical theory of organogenesis: Birefringence observations on
      regenerating leaves in the succulent, Graptopetalum paraguayense E. Walther.
AB  - Polarity shifts occur during organogenesis. The histological criterion for
      polarity is the direction of cell division. The biophysical criterion is the
      orientation of reinforcing cellulose microfibrils which lie normal to the organ
      axis and which determine the preferred growth direction. Using cell pattern to
      deduce cell lineage, and polarized light to study cellulose alignment, both
      aspects of polarity were examined in the epidermis of regenerating G.
      paraguayense. In this system new leaves and a stem arise from parallel cell files
      on a mature leaf. Large (90 degrees ) shifts in polarity occur in regions of the
      epidermis to give the new organs radial symmetry in the surface plane (files
      radiating from a pole). Study of the shifts in the epidermis showed that, during
      certain stages, shifts in the division direction are accompanied by shifts in the
      cellulose deposition direction, as expected. The new cellulose orientation is
      parallel to the new cross wall. During normal organ extension, however, shifts in
      division direction do not bring on changes in cellulose pattern. Thus the
      coupling between the two kinds of polarity is facultative. This variable relation
      is used in a biophysical model which can account for the reorganization of cell
      file pattern and cellulose reinforcement pattern into the radial symmetry of the
      new organ. 

PMID- 24302107
TI  - Ultrastructural and cytochemical aspects of induced apogamy following abscisic
      acid pre-treatment of secondary moss protonema.
AB  - Abscisic acid (ABA) treatment of secondary protonema of Physcomitrium pyriforme
      Brid in the presence of sucrose does not prevent cell division but results in
      shorter cells with vesicular cytoplasm and an accumulation of lipid. When
      transferred to sucrose medium without ABA and with low irradiance isodiametric
      intercalary cells are cut off which give rise to apogamous sporophytes either
      directly or after the formation of a small amount of callus. The organization of
      the cells leading up to the apogamous sporophyte is described. The cells
      initiating the sporophyte develop dense cytoplasm and the walls become
      labyrinthine and callosed, but they do not form any recognizable placenta. It is
      proposed that labyrinthine walls are a consequence of a perturbation of cell wall
      metabolism as growth changes from gametophytic to sporophytic. The use of the
      term "transfer cell" for this kind of cell is questioned and the need for a
      causal approach to the investigation of labyrinthine walls is stressed. 

PMID- 24302108
TI  - Auxin-stimulated ATPase in membrane fractions from pumpkin hypocotyls (Cucurbita
      maxima L.).
AB  - Membrane fractions from Cucurbita maxima hypocotyls were isolated in a medium
      which inhibits the action of endogenous phospholipases. After removal of soluble
      phosphatases by Sepharose 2B-CL column chromatography, an auxin-stimulated ATPase
      activity was found in membrane fractions from linear sucrose gradients. In the
      presence of 10(-4) M phenylacetic acid (PAA), the stimulation by indol-3-acetic
      acid (IAA) exhibited a bimodal concentration dependence with maximal stimulation
      of about 50% at 10(-6) M IAA. Without PAA, only a high concentration of 10(-4) M
      IAA was stimulatory, whereas 10(-6) M IAA had no apparent effect and 10(-8) M IAA
      exhibited weak inhibition. PAA alone had only weak or no effects. The effects of
      IAA must be considered as hormone-specific. The ATPase activity in the presence
      of 10(-4) M PAA was activated only by 2,4-dichlorophenoxyacetic acid (2,4-D), an
      active auxin analogue, but not by the inactive stereoisomers, 2,3-D and 3,5-D.
      Comparison with marker enzyme profiles suggested that part of the auxin
      stimulated ATPase was localized on plasma membranes as well as other
      compartments. Thus, the auxin-stimulated ATPase may become a useful tool in the
      investigation of the mechanism of action of auxin. 

PMID- 24302109
TI  - Ultrastructural demonstration of ferricyanide reductase (Diaphorase) activity in
      the envelopes of the plastids of etiolated barley (Hordeum vulgare L.) leaves.
AB  - Electron-dense precipitate was found consistently in the plastid envelope
      compartment in etiolated barley (Hordeum vulgare L.) leaves, incubated prior to
      fixation with succinate or malate as substrates and ferricyanide as the electron
      acceptor. Sulfhydryl reagents p-chloromercuribenzoate and N-ethylmaleimide
      abolished this reaction, while KCN did not affect it. Prefixation with 0.1%
      glutaraldehyde followed by incubation in basic media did not change the fine
      structural localization of precipitate, whereas pretreatment with 1.25%
      glutaraldehyde resulted in aspecific precipitation. Omission of the subtrate from
      the medium brought about diminished or negative reaction. Our results indicate
      that a (possibly not yet assembled) nitrate reductase complex is present in the
      plastid envelope compartment, the diaphorase part of which is responsible for the
      observed precipitation. 

PMID- 24302110
TI  - Nitrogen redistribution during grain growth in wheat (Triticum aestivum L.) :
      III. Enzymology and transport of amino acids from senescing flag leaves.
AB  - The technique of EDTA-enhanced phloem exudation (King and Zeevaart, 1974: Plant
      Physiol. 53, 96-103) was evaluated with respect to the collection and
      identification of amino acids exported from senescing wheat leaves. Whilst the
      characteristics of the exudate collected conform with many of the accepted
      properties of phloem exudate, unexpectedly high molar proportions of
      phenylalanine and tyrosine were observed. By comparing exudation into a range
      chelator solutions with exudation into water, the increased exudation of
      phenylalanine and tyrosine relative to the other amino acids occurring when
      ethylene-diaminetetracetic acid was used, was considered to an artefact.In plants
      thought to be relying heavily on mobilisation of protein reserves to satisfy the
      nitrogen requirements of the grain, the major amino acids present in flag-leaf
      phloem exudate were glutamate, aspartate, serine, alanine and glycine. Only small
      proportions of amides were present until late in senescence when glutamine became
      the major amino acid in phloem exudate (25 molar-%). Glutamine was always the
      major amino acid in xylem sap (50 molar-%).The activities of glutamine synthetase
      (EC 6.3.1.2), glutamate synthase (EC 1.4.7.1), glutamate dehydrogenase (EC
      1.4.1.3) and asparagine synthetase (EC 5.3.5.4) were measured in the flag leaf
      throughout the grain-filling period. Glutamine synthetase and glutamate-synthase
      activities declined during this period. Glutamate-dehydrogenase activity was
      markedly unchanged despite variation in the number of multiple forms visualised
      after gel electrophoresis. The activity of the enzyme reached a peak only very
      late in the course of senescence of the flag leaf. No asparagine-synthetase
      activity could be detected in the flag leaf during the grain-filling period. 

PMID- 24302111
TI  - Intracellular distribution of enzymes associated with nitrogen assimilation in
      roots.
AB  - The cellular distribution of enzymes involved in nitrogen assimilation: nitrate
      reductase (EC 1.6.6.2), nitrite reductase (EC 1.6.6.4), glutamine synthetase (EC
      6.3.1.2), glutamate synthase (EC 2.6.1.53), and glutamate dehydrogenase (EC
      1.4.1.3) has been studied in the roots of five plants: maize (Zea mays L. hybrid
      W 64A x W 182E), rice (Oryza sativa L. cv. Delta), bean (Phaseolus vulgaris L.
      cv. Contender), pea (Pisum sativum L. cv. Demi-nain), and barley (Hordeum vulgare
      L.). Initially, cell organelles were separated from soluble proteins by
      differential centrifugation. Cell organelles were also subjected to sucrose
      density gradients. The results obtained by these two methods indicate that
      nitrite reductase and glutamate synthase are localized in plastids, nitrate
      reductase and glutamine synthetase are present in the cytosol, and glutamate
      dehydrogenase is a mitochondrial enzyme. 

PMID- 24302112
TI  - Freeze-fracture observations on the plasma membrane, the cell wall and the
      cuticle of growing protonemata of Adiantum capillus-veneris L.
AB  - Using freeze-fracture electron microscopy we have examined the morphology of the
      plasma membrane and the cell wall of single-celled protonemal filaments of the
      fern Adiantum capillus-veneris grown under continuous red light. The surface of
      the protonemal cell wall is completely covered by a multilayered, lipid-like
      coat, probably consisting of cuticular waxes. The rhizoid seems to lack this type
      of coat. The cell walls of the protonemata contain 8-nm thick, randomly oriented
      fibrils. In rapidly growing protonemata the P-face of the plasma membrane
      contains both randomly distributed particles and distinct particle rosettes. The
      rosettes consist of six 8-9-nm-wide particles in a ring-like configaration and
      have an outer diameter of 24 nm. They closely resemble the particle rosettes seen
      on the P-face of the plasma membrane of green algae and of higher plants, which
      recently have been implicated in the synthesis of cellulose fibrils. Within 20
      MUm from the tip of the protonemata, and coinciding with the region of maximal
      cell-wall growth and expansion and thus cellulose-fibril synthesis, the greatest
      density of rosettes (20/MUm(2)) is observed. Beyond 20 MUm from the tip this
      number drops rapidly to near zero at 50 MUm. The rosettes have a tendency to form
      small, irregular clusters, but only very rarely are three or more rosettes found
      in a row or in a geometrical pattern. Our measurements of the size and the
      density of the randomly distributed plasma membrane particles indicate that the
      tip region must be specialized with respect to other plasma-membrane activities
      as well. Thus the tip region contains not only the highest density of randomly
      destributed intramembrane particles, but also particles of different sizes than
      those found elsewhere in the plasma membrane. 

PMID- 24302113
TI  - Pyrenoid protein from the brown alga Pilayella littoralis.
AB  - Characterization by peptide mapping and amino acid analysis of the two major
      pyrenoid polypeptides from the brown alga Pilayella littoralis shows that they
      are very similar to the subunits of ribulose-1,5-bisphosphate carboxylase (EC
      4.1.1.39) from this alga. The observed similarities are discussed in relation to
      previous pyrenoid protein characterization from members of the Chlorophyceae. 

PMID- 24302114
TI  - Wound ethylene and 1-aminocyclopropane-1-carboxylate synthase in ripening tomato
      fruit.
AB  - Ethylene production, 1-aminocyclopropane-1-carboxylic acid (ACC) levels and ACC
      synthase activity were compared in intact and wounded tomato fruits (Lycopersicon
      esculentum Mill.) at different ripening stages. Freshly cut and wounded pericarp
      discs produced relatively little ethylene and had low levels of ACC and of ACC
      synthase activity. The rate of ethylene synthesis, the level of ACC and the
      activity of ACC synthase all increased manyfold within 2 h after wounding. The
      rate of wound-ethylene formation and the activity of wound-induced ACC synthase
      were positively correlated with the rate of ethylene production in the intact
      fruit. When pericarp discs were incubated overnight, wound ethylene synthesis
      subsided, but the activity of ACC synthase remained high, and ACC accumulated,
      especially in discs from ripe fruits. In freshly harvested tomato fruits, the
      level of ACC and the activity of ACC synthase were higher in the inside parts of
      the fruit than in the pericarp. When wounded pericarp tissue of green tomato
      fruits was treated with cycloheximide, the activity of ACC synthase declined with
      an apparent half life of 30-40 in. The activity of ACC synthase in cycloheximide
      treated, wounded pericarp of ripening tomatoes declined more slowly. 

PMID- 24302115
TI  - Osmoregulation, solute distribution, and growth in soybean seedlings having low
      water potentials.
AB  - Soybean (Glycine max (L.) Merr.) seedlings osmoregulate when the supply of water
      is limited around the roots. The osmoregulation involves solute accumulation
      (osmotic adjustment) by the elongating region of the hypocotyls. We investigated
      the relationship between growth, solute accumulation, and the partitioning of
      solutes during osmoregulation. Darkgrown seedlings were transplanted to
      vermiculite containing 1/8 (0.13 x) the water of the controls. Within 12-15 h,
      the osmotic potential of the elongating region had decreased to-12 bar, but it
      was-7 bar in the controls. This osmoregulation involved a true solute
      accumulation by the hypocotyls, since cell volume and turgor were virtually the
      same regardless of the water regime. The hypocotyls having low water potentials
      elongated slowly but, when deprived of their cotyledons, did not elongate or
      accumulate solute. This result indicated a cotyledonary origin for the solutes
      and a dependence of slow growth on osmotic adjustment. The translocation of
      nonrespired dry matter from the cotyledons to the seedling axis was unaffected by
      the availability of water, but partitioning was altered. In the first 12 h, dry
      matter accumulated in the elongating region of the 0.13 x hypocotyls, and osmotic
      adjustment occurred. The solutes involved were mostly free amino acids, glucose,
      fructose, and sucrose, and these accounted for most of the increased dry weight.
      After osmotic adjustment was complete, dry matter ceased to accumulate in the
      hypocotyls and bypassed them to accumulate in the roots, which grew faster than
      the control roots. The proliferation of the roots resulted in an increased
      root/shoot ratio, a common response of plants to dry conditions.Osmotic
      adjustment occurred in the elongating region of the hypocotyls because solute
      utilization for growth decreased while solute uptake continued. Adjustment was
      completed when solute uptake subsequently decreased, and uptake then balanced
      utilization. The control of osmotic adjustment was therefore the rate of solute
      utilization and, secondarily, the rate of solute uptake. Elongation was inhibited
      by unknown factors(s) despite the turgor and substrates associated with osmotic
      adjustment. The remaining slow elongation depended on osmotic adjustment and
      represented some optimum between the necessary inhibition for solute accumulation
      and the necessary growth for seedling establishment. 

PMID- 24302116
TI  - Partial purification of a hemagglutinin associated with cell walls from
      hypocotyls of Vigna radiata.
AB  - The hemagglutinin (lectin) associated with the cell walls of hypocotyls from
      Vigna radiata was greatly purified. At every stage in the purification the
      hemagglutinating activity coincided exactly with alpha-galactosidase activity.
      This suggests that, similar to the seed lectin of the same plant, both activities
      might be present in the same molecule which has a molecular weight of about
      170,000. When the purification was performed in the absence of d-galactose and 2
      mercaptoethanol (method A), the native molecule appeared to dissociate into
      smaller units exhibiting preferentially either alpha-galactosidase or lectin
      properties. This indicates that the subunits in the native molecule might be
      functionally different. The lectin appears to be bound to the cell wall and can
      rebind to cell walls without participation of its sugar binding sites. 

PMID- 24302117
TI  - Absence of fluence rate dependency of phytochrome modulation of stem extension in
      light-grown Sinapis alba L.
AB  - In background white light, supplementary far-red (lambdamax 700 nm) is an order
      of magnitude less effective than supplementary far-red (lambdamax 739 nm) in the
      stimulation of stem extension in Sinapis alba. The relationship between
      phytochrome photoequilibrium and extension rate increase for the two
      supplementary far-red treatments is, however, very similar. This evidence
      indicates that phytochrome cycling is not involved in the phytochrome control of
      stem extension in light-grown Sinapis alba and that the response to supplementary
      far-red light is not fluence rate (irradiance) dependent. 

PMID- 24302118
TI  - Properties and stability of blueberry anthocyanin--bovine serum albumin
      nanoparticles.
AB  - BACKGROUND: Since they would be easily decomposed under alkaline conditions,
      anthocyanins are likely to have poor oxidation stability. However, encapsulated
      with protein molecules, anthocyanins could be protected owing to the slowing down
      of the oxidation process. In this study, the characteristics of nanoparticles,
      formed by the interactions of anthocyanins with bovine serum albumin (BSA), and
      their impact on the oxidation stability of anthocyanins were investigated.
      RESULTS: Both BSA and anthocyanin-bound BSA could form self-assembled
      nanoparticles in phosphate buffer (pH 7.4), and the particle size of anthocyanin
      bound BSA (20-25 nm) was smaller than that of BSA (35-40 nm). The ratio of BSA to
      anthocyanin was 1:10. The radical scavenging rates of BSA-bound anthocyanin were
      lower than those of the unbound anthocyanin. No significant difference was seen
      in the stability between the unbound and BSA-bound anthocyanin in the simulated
      gastric system, whereas a difference was seen in the simulated intestinal system.
      The amount of unbound anthocyanin decreased by 70% after 6 h, while BSA-bound
      anthocyanin was almost unchanged. BSA exhibited a remarkable effect on the
      oxidation stability of anthocyanins. CONCLUSION: BSA nanocarriers could improve
      the stability of anthocyanin under neutral conditions, which has great potential
      for applications.

PMID- 24302119
TI  - Ultrasound-guided botulinum toxin injection to treat a parotid fistula following
      gunshot injury.
AB  - Parotid fistula is a rare but very distressing sequelum of post-operative or
      traumatic injuries. The management of these injuries has been reported in the
      literature previously and techniques employed include pressure dressings, surgery
      and more recently botulinum toxin A (BTA) injections. We present a patient who
      developed a parotid fistula as a late complication of an extensive gunshot injury
      to the face with subsequent successful management with ultrasound-guided
      intraglandular injections of BTA. This case demonstrates that the BTA injection
      is an effective and safe method under ultrasound guidance and should considered
      as a first-line treatment option for the treatment of salivary fistulas. 

PMID- 24302120
TI  - An evaluation of the potential use of Cryptosporidium species as agents for
      deliberate release.
AB  - INTRODUCTION: We evaluated the potential of Cryptosporidium spp. for intentional
      transmission as a terrorist tactic in asymmetric conflicts in terms of the
      recognised optimum conditions for biological warfare. METHODS: Published and
      widely accepted criteria regarding the optimum conditions for the success of
      biological warfare based on experience from passive biological warfare research
      were applied to hypothetical intentional Cryptosporidium spp. transmission.
      RESULT: The feasibility of the use of Cryptosporidium spp. transmission for
      terrorist purposes was established. Particularly on tropical deployments with
      poor hygiene conditions, such attacks might have a good chance of remaining
      undetected as a deliberate terrorist attack. CONCLUSIONS: Intentional
      transmission should be suspected in cases of sudden outbreaks of
      cryptosporidiosis, particularly where adequate food and drinking water hygiene
      precautions are being enforced. Appropriate diagnostic procedures should be
      available so that the diagnosis is not missed.

PMID- 24302121
TI  - Why stop self-injuring? Development of the reasons to stop self-injury
      questionnaire.
AB  - We developed a measure of reasons to refrain from nonsuicidal self-injury (NSSI),
      the Reasons to Stop Self-Injury Questionnaire (RSSIQ), and examined how such
      reasons are associated with vulnerability versus resiliency for NSSI. Following
      qualitative item generation, we explored the factor structure, reliability, and
      convergent validity of the RSSIQ in 218 self-injuring undergraduates. In Study 2,
      we confirmed the hierarchical factor structure in 146 self-injuring individuals.
      In Study 3, we examined the incremental predictive validity of the RSSIQ. These
      studies resulted in a 40-item inventory with nine subscales and two higher-order
      factors. Resiliency-related reasons to stop NSSI were associated with greater
      hopefulness, social support, and adaptive coping, and prospectively protected
      against NSSI 3 months later, while vulnerability-related reasons were associated
      with greater psychopathology and dysfunctional coping, and predicted more chronic
      and severe NSSI. These studies, and the RSSIQ, can enhance the assessment and
      treatment of NSSI by clarifying motivations to stop NSSI. 

PMID- 24302122
TI  - Effects of Noncontingent Social Interaction on Immediate and Subsequent
      Engagement in Vocal and Motor Stereotypy in Children With Autism.
AB  - This study evaluated the effects of noncontingent social interaction (SI) on
      immediate and subsequent engagement in vocal and motor stereotypy in three
      children with autism. During SI, a therapist delivered continuous interaction in
      the form of reading aloud from a KindleTM e-reader. Results showed that when
      compared with a no-interaction baseline sequence, SI decreased immediate
      engagement vocal stereotypy for all three participants without increasing
      subsequent engagement for any participant. Furthermore, SI also increased
      immediate engagement in motor stereotypy for one participant, decreased immediate
      engagement in motor stereotypy for two participants, but did not increase
      subsequent engagement in motor stereotypy for any participant. Some clinical
      implications and limitations of the findings are discussed. 

PMID- 24302124
TI  - The impact of structural polydispersivity on the surface electrostatic potential
      of nanodiamond.
AB  - The discovery of the multipolar surface electrostatic potential on faceted
      diamond nanoparticles explained numerous observations over the past decades, but
      also raised questions as to how it could be reconciled with seemingly
      contradictory observations of micron sized diamond and bulk diamond surfaces. It
      was also unclear how surface electrostatic potential would vary for more quasi
      spherical shapes, and derivatives of the ideal truncated octahedron. Here we
      present new results examining the size-dependence of the multi-polar surface
      electrostatic potential up to experimentally relevant sizes, and explore the
      impact of {110} facets which have been shown to present in reasonable quantities
      (experimentally). We have used computational methods that are consistent with
      previous work to allow for a direct comparison, and show that both particle size
      and the fraction of {110} facets on nanodiamond play a critical role in the
      surface charge. When the particle size is below ~2.5 nm multipoles are likely to
      dominate, but over ~3.0 nm the {110} facets efficiently neutralize the charges
      leading to a practically monopolar distribution, consistent with observations at
      other length scales.

PMID- 24302123
TI  - Discovery of new G-quadruplex binding chemotypes.
AB  - We report here on the discovery and preliminary evaluation of a novel non
      macrocyclic low molecular weight quadruplex-stabilizing chemotype. The lead
      compounds, based on a furan core, show high G-quadruplex stabilisation and
      selectivity as well as potent in vitro anti-proliferative activity. 

PMID- 24302125
TI  - Sex pheromone of oriental armywormMythimna separata Walker.
AB  - In the mainland of China, the male Oriental armyworm was not attracted to the sex
      pheromone components (Z)-11-hexadecenyl acetate and (Z)-11-hexadecenol identified
      by Takahashi et al. in 1979. By means of EAG, GC, and GC-MS techniques, (Z)-11
      hexadecenal, hexadecenal, and (Z)-11-hexadecenol were found in female gland
      washings, and encouraging captures were obtained in preliminary field trapping. 

PMID- 24302126
TI  - Sex pheromone components of purple stem borerSesamia inferens (Walker).
AB  - The pheromone of the female purple stem borer,Z-11-hexadecenyl acetate,
      identified by Nesbitt, was not active in field trapping in China. From EAG, TLC,
      GC, and GC-MS tests, we found thatZ-11-hexadecenyl acetate,Z-11-hexadecenol, andZ
      11-hexadecenal were the pheromone components, and the preferred blend ratio in
      field tests was 4?1?0.1. The number of captures of the later generations was
      substantially lower than that of the overwintered generation. 

PMID- 24302127
TI  - Identification of sex pheromone components from pheromone gland volatiles of the
      tomato looper,Plusia chalcites (Esp.).
AB  - The sex pheromone glands ofPlusia chalcites release, dodecyl acetate, (Z)-7
      dodecenyl acetate, (Z)-9-dodecenyl acetate, 11-dodecenyl acetate, (Z)-8
      tridecenyl acetate, and (Z)-9-tetradecenyl acetate. A combination of capillary
      GC, GC-MS, and dimethyl disulfide derivatization enabled a rigorous
      identification of all these compounds, some of which were previously found in
      gland extracts. Bioassays in a flight tunnel showed that a ternary blend of (Z)-7
      dodecenyl acetate, (Z)-9-dodecenyl acetate, and (Z)-9-tetradecenyl acetate
      elicited directed flights from 85 to 100% of the males tested and elicited
      copulation attempts, at the end of the flights, from 44 to 74% of the males
      tested. This blend was equal in activity to the natural gland extract. Addition
      of the other acetates had only a slight influence on the activity of this
      mixture. Substitution of either (Z)-9-dodecenyl acetate or (Z)-9-tetradecenyl
      acetate in this blend by 11-dodecenyl acetate gave two ternary mixtures which
      also elicited high levels of courtship activity, almost as high as that of the
      original blend. Addition of (Z)-7-dodecenyl alcohol inhibited almost totally the
      flight activity of males. 

PMID- 24302128
TI  - Role of female-produced sex pheromone in behavioral reproductive isolation
      betweenTrichoplusia ni (Hubner) andPseudoplusia includens (Walker) (Lepidoptera:
      Noctuidae, plusiinae).
AB  - In laboratory flight tunnel bioassays, response rates of male cabbage
      looper,Trichoplusia ni (Hubner), to female soybean looper,Pseudoplusia includens
      (Walker), were similar to response rates of maleT. ni to conspecific females for
      plume tracking and source contact. Male soybean loopers, however, exhibited a
      greatly reduced response to female cabbage loopers compared to conspecific
      females. Similar differences were observed in male responses to extracts of
      female abdominal tips. Studies of flight tunnel responses of male soybean loopers
      to the different chemicals known to be components of the female cabbage looper
      sex pheromone indicated that the reduction in response was due to inhibitory
      effects of (Z)-5-dodecen-1-ol acetate and (Z)-9-tetradecen-1-ol acetate, when
      added singly to (Z)-7-dodecen-1-ol acetate (major component of both species) at
      release rates and at ratios close to those observed in female cabbage loopers. 

PMID- 24302129
TI  - Reinvestigation confirms action of Delta11-desaturases in spruce budworm moth sex
      pheromone biosynthesis.
AB  - The biosynthesis of a large number of sex pheromone components of various moth
      species has been shown to start with common fatty acids and involve chain
      shortening by two carbons and introduction of a double bond at the 11-12
      position. A recent report indicates that one of these common components, (E)-11
      tetradecenyl acetate, is present in the eastern spruce
      budworm,Choristoneurafumiferana, but is not made by this pathway. Reinvestigation
      of this insect using in vivo and in vitro techniques indicates that the acetate
      indeed is made by a sequence of reactions similar to that used in other
      leafroller moths. In fact, evidence was found for the presence of several Delta11
      desaturase systems in spruce budworm. One produced a large quantity of (Z)-11
      hexadecanoic acid, and another produced (E)-11-tetradecanoic acid. It is not
      known if the small amount of (Z)-11-tetradecanoic acid is produced by either of
      those two systems or by a third system. A comparison with other species showed
      that cabbage looper moths have only the first system, redbanded leafroller moths
      use the last two systems, and European corn borer moths have all three. 

PMID- 24302130
TI  - An interactive video-computer tracking system for quantification of locomotor
      behavior.
AB  - We have developed a flexible, moderately priced, behavioral analysis system which
      has been used to determine the response of salmonids to certain olfactory
      stimulants. The system, which we call ITS for interactive computer-video tracking
      system, consists of a 128K Apple IIe computer with software, a video camera and
      videocassette recorder, and a special-effects generator. Experiments are video
      taped and then, during playback, the special effects generator is used to
      simultaneously display the video image and the graphics output of the computer on
      a monitor. The user tracks the animal of interest using an electronic pen, and
      the position of that animal in the test chamber, in the form ofx-y coordinates,
      is determined by the computer at user-defined time intervals. When tracking is
      complete, a plot of the track of the animal is printed within the outline of the
      test chamber. The following data can also be calculated: swimming velocity,
      distance from a predetermined point in the chamber (for example, olfactory
      stimulant source), and time spent in a given area. These variables can be
      calculated over any chosen time periods and/or for the entire experiment. ITS has
      numerous advantages over commercially available devices that perform similar
      tasks. First, it is relatively inexpensive, especially if one already owns video
      equipment and a computer. Second, it can analyze many types of experiments that
      can be stored on video tape, including field observations or manipulations.
      Third, because it is not automated, it is easy to track multiple objects, even if
      their tracks cross or are not easily located against a low-contrast background.
      Finally, because whole images do not have to be digitized, and data collection
      intervals can be adjusted by the user, it is possible to analyze very long
      experiments with a microcomputer. In this paper we describe ITS and then we
      demonstrate how we have used it to demonstrate that changes in ambient pH alter
      the behavioral response of juvenile Atlantic salmon to olfactory stimuli. 

PMID- 24302131
TI  - Differences in attraction to semiochemicals present in sympatric pine shoot
      beetles,Tomicus minor andT. piniperda.
AB  - The chemical ecology of host- and mate-finding in the pine shoot beetles,Tomicus
      minor andT. piniperda, was studied in southern Sweden. Beetles were collected in
      the field from defined attack phases on Scots pine. Using gas chromatography-mass
      spectroscopy, a number of oxygen-containing monoterpenes, e.g., 3-carene-10-ol,
      myrtenol,trans-verbenol, and verbenone, were identified from hindgut extracts of
      both sexes of both species. Compared toT. minor,T. piniperda contained additional
      compounds and in larger amounts. The amounts were highest in both species at the
      time when the beetles had bored into contact with the resin-producing xylem
      phloem tissue. The synthesis of (1S,6R)-3-carene-10-ol by photooxidatipn of (+)
      (1S,6R)-3-carene is described. In comparative electroantennogram (EAG)
      measurements on males and females of both species, the most active of the tested
      compounds wastrans-verbenol. Laboratory bioassays of walking beetles showed
      thatT. piniperda was attracted to uninfested pine logs.T. minor was more strongly
      attracted to pine logs infested with females than to uninfested pine logs,
      indicating a female-produced aggregation pheromone. Field tests confirmed thatT.
      piniperda was strongly attracted to pine logs. The attraction ofT. minor to logs
      was significant only when logs were combined with racemictrans-verbenol and
      (1S,6R)-3-carene-10-ol.T. minor was also attracted to a combination of these
      monoterpene alcohols alone. We suggest that host and mate location inT. piniperda
      is achieved by means of a kairomone composed of host monoterpenes, whileT. minor
      utilizes a primitive pheromone synergized by host odors. Evolution of host
      colonization strategies of the two beetles are discussed. 

PMID- 24302132
TI  - Patterns and sources of leaf tannin variation in yellow birch (Betula
      allegheniensis) and sugar maple (Acer saccharum).
AB  - Leaves from forest-grown sugar maple (Acer saccharum Marsh) and yellow birch
      (Betula allegheniensis Britt.) trees were analyzed for four tannin measures
      (hydrolyzable and condensed tannins, total phenolics, and protein binding) at
      three times during the growing season. Fifteen-year-old half-sib sugar maples
      from four provenances, representing the geographical extremes of the sugar maple
      range and growing in a common garden, were examined for the same traits. We found
      no significant geographic or seed source component to variation in three of the
      four tannin measures. We found significant seasonal changes in both birch and
      maple leaf tannins. Withincanopy leaf tannin variation tended to obscure
      differences between trees in maple, but in birches between-tree differences in
      leaf tannin content were more readily found. We also found a significant negative
      correlation between leaf protein binding capacity and leaf wet weight. 

PMID- 24302133
TI  - Formic acid in caustic cephalic secretions of stingless bee,Oxytrigona
      (Hymenoptera: Apidae).
AB  - The cephalic extracts of two species in the stingless bee genusOxytrigona were
      analyzed. Extracts made in diethyl ether, and then derivatized with
      diphenyldiazomethane, revealed large quantities of formic acid, potentially a
      major defensive secretion of this stingless bee group. We additionally identify
      several hydrocarbons, aldehydes, ketones, and acetates. Novel diketones
      identified by others were detected in both species. 

PMID- 24302134
TI  - Feeding deterrent compounds to the boll weevil,Anthonomus grandis Boheman in Rose
      of-Sharon,Hibiscus syriacus L.
AB  - The Rose-of-Sharon,Hibiscus syriacus (L.), can be a significant alternate host
      plant for the boll weevil,Anthonomus gradis (Boh.). Boll weevils are known to be
      deterred from feeding and ovipositing in the buds unless the calyx is removed.
      This investigation was initiated to identify calyx allelochemicals that deter
      feeding with the eventual strategy of breeding for cotton lines high in these
      allelochemicals in the appropriate tissues. The feeding deterrency of calyx
      tissue from the buds of Rose-of-Sharon for the boll weevil was confirmed. The
      most active deterrent fraction was found to contain mostly fatty acids and their
      methyl esters. Saturated fatty acids and their methyl esters were generally found
      to be stimulatory, while the unsaturated species were found to be deterrent.
      Higher quantities of the fatty acids, particularly the unsaturated species, were
      found in Rose-of-Sharon calyx tissue than in the buds without calyx. This
      supports the hypothesis developed through the isolational work and testing of
      standards that the unsaturated fatty acids are significant deterrents of boll
      weevil feeding. 

PMID- 24302135
TI  - Pheromonal basis of courtship behavior in two gypsy moth parasitoids:Brachymeria
      intermedia (Nees) andBrachymeria lasus (Walker) (Hymenoptera: Chalcididae).
AB  - The pheromonal basis of the courtship behavior of two gypsy moth
      parasitoids,Brachymeria intermedia andBrachymeria lasus, was traced to a single
      component in each case. This component was isolated by a combination of
      absorption and gas-liquid chromatography and shown to elicit some of the
      courtship behavior typical of these species. Bioassays of extracts from several
      independent techniques for sequestering pheromones, as well as interspecific
      assays, support this conclusion. Comparative analyses of both male and female
      extracts by capillary chromatography show the uniqueness of the pheromonal peak
      to the female volatile profile. 

PMID- 24302136
TI  - Temporal patterns of sex pheromone titers and release rates inHolomelina lamae
      (Lepidoptera: Arctiidae).
AB  - Six hydrocarbon components (2-methylhexadecane,n-heptadecane, 2
      methylheptadecane, 2-methyloctadecane,n-nonadecane, and 2-methylnonadecane) were
      identified in sex-pheromone gland extracts and in airborne collections
      ofHolomelina lamae. Low variability in the ratio of components among individuals
      indicates tight regulation of blend composition. Minor changes were evident in
      the quantity and ratio of the blend as a function of time of day. Based on gland
      extracts, the total quantity of the six components increased from day 1 (X = 6299
      ng) to day 4 (X = 7498 ng) and subsequently decreased. No significant
      correlations were found between total gland contents and wet or dry weights of
      moths. Emission rates ofH. lamae females were determined from pheromone adsorbed
      onto Porapak Q. Quantities released peaked shortly after the onset of calling and
      decreased rapidly as calling continued. Peak release rates ranged from 13 to 350
      ng/10 min, and from 37 to 835 ng/60 min. Noncalling females did not emit
      detectable quantities of pheromone. Based on release rates and the rate of
      pulsation of the abdominal tip, the average amount released per pulse is not
      constant. The mean ratio of components released (0.78?7.45? 84.80?2.84?2.59?1.53)
      was not very different from the ratio of components in gland extracts of 2-day
      old females (0.70?4.19?90.12? 1.65?1.91?1.42). We propose that the blend is
      atomized rather than volatilized from the gland, thus retaining nearly the same
      ratios in the female's effluvium as in her gland. 

PMID- 24302137
TI  - Allomonal functions of steroid hormone, antheridiol, in water moldAchlya.
AB  - The steroid hormone antheridiol has previously been shown to play a number of key
      roles in regulating development of the male sex organs, antheridia, of the water
      moldAchlya ambisexualis. We now demonstrate that synthetic antheridiol can
      inhibit both sexual (determined by oogonial counts) and asexual reproduction
      (determined by counts of asexual spores) in an isolate of the homothallic
      speciesA. heterosexualis. The implications of this dual role of antheridiol as
      hormone and allomone are discussed. 

PMID- 24302138
TI  - Misleading the Colorado potato beetle with an odor blend.
AB  - Walking tracks of Colorado potato beetles,Leptinotarsa decemlineata Say, were
      recorded on a locomotion-compensator in response to wind, odors of host
      plantsSolanum tuberosum L. and nonhost plantsLycopersicon hirsutum f.glabratum
      C.H. Mull, and to mixtures of these plant species. Host-plant odor induced
      positive anemotactic responses in starved females, whereas odor of the nonhostL.
      hirsutum was neither repellent nor attractive. The attractiveness of host-plant
      odor, however, was neutralized in the odor blend of plant species. Masking the
      attractive host-plant odor will hinder the beetle's searching for host-plant
      patches, and this principle may be exploited in pest control by mixed cropping. 

PMID- 24302139
TI  - Airborne differences in odors emitted byRattus norvegicus in response to reward
      and nonreward.
AB  - To test the hypothesis that rats (Rattus norvegicus) emit airborne, differential
      odors in response to reward and nonreward, donor rats received random sequences
      of rewarded and nonrewarded placements in small compartments and an airstream
      transported odors from these compartments to test rats in a separate chamber.
      When donors remained in the compartments during, or were removed just prior to,
      air transport, test rats utilized transported odors as discriminative cues
      signaling their own reward and nonreward for a lever-press response. When the
      airstream was passed through a clean compartment containing paper flooring
      extracted from donor compartments, test rats were not able to discriminate. Test
      trials to assess for control by food odors suggest that donor-produced odors,
      rather than food odors per se, provided the discriminative signals for test rats.
      Results confirm the existence of somewhat volatile, although apparently stable,
      odors emitted in response to reward and nonreward, and implicate a differential
      in amount and/or type of odor produced by donors to these two events as the
      source of discriminative control. 

PMID- 24302140
TI  - Sex pheromone of blackheaded fireworm,Rhopobota naevana (Lepidoptera:
      Tortricidae), a pest of cranberry.
AB  - Splitless capillary gas chromatography indicated the presence of (Z)- and (E)-11
      tetradecenyl acetate and (Z)-11-tetradecenyl alcohol in the washes of female
      abdominal tips of the blackheaded fireworm,Rhopobota naevana (Hubner). Gas
      chromatography combined with mass spectroscopy confirmed the presence of
      tetradecenyl acetate in extracts of female tips. The low levels observed in these
      extracts (< 1 ng/female equivalent), prevented further chemical and spectroscopic
      identification. These materials were found to be stimulatory at low levels in
      electroantennogram studies. A combination of 9 MUg of (Z)-11-tetradecenyl acetate
      and 3 MUg of (Z)-11-tetradecenyl alcohol on rubber septa in wing traps provided
      an effective attractant. (Z)-9-Dodecenyl acetate, a previously reported
      attractant, did not significantly increase field trapping catches when added to
      the binary mixture, but was found to enhance trap catches when added to each of
      the primary components. 

PMID- 24302141
TI  - Evidence for chemical defense in tropical green algaCaulerpa ashmeadii
      (Caulerpaceae: Chlorophyta): Isolation of new bioactive sesquiterpenoids.
AB  - Results of field feeding preference studies with 12 species of tropical green
      algae of the genusCaulerpa showed thatC. ashmeadii was preferred least by
      herbivorous fishes. Chemical investigations ofC. ashmeadii demonstrated the
      presence of high concentrations of sesquiterpenoid metabolites. The chemical
      isolation and structural elucidation of five majorC. ashmeadii metabolites, as
      well as the results of field feeding preference, antimicrobial, and
      ichthyotoxicity assays demonstrating the biological activities of these
      metabolites are reported here. 

PMID- 24302142
TI  - Identification of sex pheromone components of darksided cutworm,Euxoa messoria,
      and modification of sex attractant blend for adult males.
AB  - Eleven "pheromone-like" compounds were identified in excised abdomen tip extracts
      of calling adult females of darksided cutworm,Euxoa messoria (Harris). The
      essential pheromone components were (Z)-7- and (Z)-11-hexadecenyl acetates in a
      ratio of 1?40, which agreed with an attractant blend developed empirically by
      field testing the attractancies of synthetic blends. The pheromone component, (Z)
      11-hexadecenol, improved the attraction of darksided cutworm males whereas the
      components (Z)-9-tetradecenyl acetate and (Z)-7-dodecenyl acetate inhibited their
      attraction. The other "pheromone-like" compounds identified in the female
      extracts had no obvious effect on the attraction of darksided cutworm males.
      Three compounds that functioned as parapheromones when substituted for (Z)-7
      hexadecenyl acetate in the two-component blend were (Z)-7-pentadecenyl, (Z)-7
      tetradecenyl, and (Z)-7-tridecenyl acetates. (Z)-11-hexadecenal was not detected
      in the female extracts, but it had a synergistic effect on the attraction of
      darksided cutworm moths and inhibited the attraction of male moths of a nontarget
      species,Helotropha reniformis (Grote). As a trap bait for monitoring purposes, we
      recommend a four-component blend of (Z)-7-hexadecenyl acetate, (Z)-11-hexadecenyl
      acetate, (Z)-11-hexadecenol, and (Z)-11-hexadecenal at 12.5, 500, 1, and 10
      MUg/red rubber septum dispenser containing 5 MUg of antioxidant 2,6-tert-butyl-4
      methyl phenol. This blend is effective under field conditions for at least six
      weeks. 

PMID- 24302143
TI  - Attraction of predatorily naive postlarval lobsters to extracts of metabolites of
      common prey:Mytilus edulis, Mya arenaria, Cancer irroratus, andAsterias vulgaris.
AB  - Postlarval lobsters (4th-7th stage) exclusively fed frozen brine shrimp (Artemia
      saline) were assayed for food-search response to extracts and metabolites from
      four common prey: soft clams (Mya arenaria), blue mussels (Mytilus edulis), rock
      crabs (Cancer irroratus), and sea stars (Asterias vulgaris). Concentrations of
      soluble primary amines, protein, and ammonia in prey tissues and metabolites were
      determined. No significant responses were observed for any prey metabolites
      diluted to 1 and 10%, while onlyA. vulgaris evoked a significant response at full
      strength, suggesting that predatorily naive lobsters have yet to develop more
      pronounced chemosensory responses shown by field-collected lobsters. Removal of
      protein with retention of small-molecular-weight polar molecules did not appear
      to affect response to prey extracts. EC50s, as micromoles per liter amines,
      computed from prey extract dose-response curves indicate differences per unit
      amine between prey extracts, withA. vulgaris extract more potent as an attractant
      than either bivalve extract.C. irroratus extract was equally attractive as the
      other three extracts. Ammonia levels excreted into seawater over 3 hr were
      similar for all prey species, while soluble primary amines and proteins were
      undetectable. Ammonia and protein per gram whole prey varied significantly
      between extracts of prey species, while primary amines were similar. Lobsters may
      be attracted preferentially to carrion species with higher concentrations of
      amines and/or higher potency of attractants per unit amine. 

PMID- 24302144
TI  - Development of chemically mediated prey-search response in postlarval lobsters
      (Homarus americanus) through feeding experience.
AB  - Postlarval lobsters were fed live amphipods (Gammarus oceanicus), soft clam spat
      (Mya arenaria), or frozen brine shrimp (Artemia salina) for five weeks in order
      to determine by behavioral bioassay if chemically mediated prey-search behavior
      is established by feeding experience. Chemosensory responses of predatorily naive
      lobsters to live clam and amphipod metabolites were low and erratic. After five
      weeks, amphipod-fed lobsters had developed strong responses towards amphipod
      metabolites but not clam metabolites. In contrast, clam-fed lobsters did not
      develop responses to either prey. Chemical fractionation of amphipod metabolites
      indicated that attractants were confined to the same fraction as for prey
      extracts, i.e., polar, low-molecular-weight compounds. Survival (80-90%) was
      similar for each diet group; growth was greatest for amphipod-fed lobsters
      (100%), followed by clam-fed lobsters (72%) and brine shrimp-fed lobsters (18%);
      and feeding rates increased for amphipod-fed lobsters and decreased for clam-fed
      lobsters. Coloration of lobsters indicated that only amphipod diet provided
      desirable pigments. Differences in ingestive conditioning results between clamfed
      and amphipod-fed lobsters may have been related to (1) clam metabolites being
      qualitatively or quantitatively less attractive than amphipod metabolites or (2)
      differences in the predisposition of lobsters to show ingestive conditioning to
      different prey and their associated metabolites as a function of quality of prey
      as a diet. 

PMID- 24302145
TI  - Blackheaded fireworm: Laboratory and field studies of its sex pheromone.
AB  - Electroantennogram (EAG) responses of maleRhopobota naevana (Hubner), the
      blackheaded fireworm, to all of the monoene straightchain 12- and 14-carbon
      alcohols and acetates implicated (Z)-11-tetradecenl-1-ol (Z11-14?OH) and its
      acetate (Z11-14?Ac) as sex pheromone components.Z11-14?Ac produced the strongest
      EAG response of all compounds tested. Gas chromatography-mass spectrometry (GC
      MS) analysis of extract of female sex pheromone glands (SPG) confirmed the
      presence ofZ11-14?OH (125 pg/female) andZ11-14?Ac (600 pg/female) (all other
      monoenes had different retention times). In field tests, traps baited withZ11
      14?OH alone captured males, but traps baited withZ11-14?Ac alone did not. Traps
      baited with a combination ofZ11-14?OH andZ11-14?Ac in various ratios did not
      produce better trap catches thanZ11-14?OH alone. (Z)-9-Dodecen-1-ol acetate (Z9
      12?Ac), reported by others to be a field attractant, did not produce trap catch
      in our tests, but in combination withZ11-14? OH (98?2 in septa corresponding to
      95:5 in vapor,Z11-14?OH toZ9-12?AC) produced a sevenfold increase in catch
      overZ11-14?OH alone. IfZ9-12?AC had been present in extract of SPG at 2-5% ofZ11
      14?OH, it would not have been detected in our GC-MS experiment. 

PMID- 24302146
TI  - Implications of soluble tannin-protein complexes for tannin analysis and plant
      defense mechanisms.
AB  - Factors which establish whether tannin and protein interact to form soluble
      complexes or precipitates were identified. The ratio of tannin to protein in the
      reaction mixture influenced solubility of the tannin-protein complexes. At
      protein-to-tannin ratios larger than the optimum ratio, or equivalence point,
      soluble tannin-protein complexes apparently formed instead of insoluble
      complexes. Several other factors influenced the amount of protein precipitated by
      tannin-containing plant extracts, including the length of the reaction time and
      the conditions of the tannin extraction. The analytical and ecological
      significances of soluble complexes were considered. A titration method which
      allows simultaneous determination of the equivalence point and assessment of the
      protein-precipitating capacity of any plant extract was developed. It was
      postulated that in vivo, tannin and protein may not only form insoluble complexes
      with antinutritional effects, but may also form soluble complexes which have
      unknown metabolic effects. 

PMID- 24302147
TI  - Responses ton-dipropyl disulfide by ovipositing onion flies: Effects of
      concentration and site of release.
AB  - Onion fly females,Delia antiqua (Diptera: Anthomyiidae) laid the most eggs on
      ovipositional dishes havingn-dipropyl disulfide (Pr2S2) release rates of 1-6
      ng/sec from polyethylene capsules placed beneath a sand substrate. When dipropyl
      disulfide was released from the wax coating of surrogate foliage rather than from
      the substrate, ovipositing females again responded differentially to various
      concentrations, laying more eggs around stems containing 0.075 and 0.089 mg/stem.
      Factorial combinations of several concentrations released from surrogate foliage
      and substrate showed that releases from surrogate foliage stimulated four times
      more egg-laying than releases from the substrate. Females tended to lay more eggs
      around surrogate stems having Pr2S2 at the base rather than on the upper half of
      foliage. Observations of individual females performing preovipositional examining
      behaviors on Pr2S2-treated surrogate stems indicated that females tended to land
      on the upper portions of the foliage, but after landing, spent most of their time
      examining areas of soil and surrogate within 1 cm of the soil-surrogate foliage
      interface. Surrogate stems provide a realistic context for investigating effects
      of plant chemicals on host-acceptance behaviors. 

PMID- 24302148
TI  - Kinetic resolution of secondary alcohols with commercial lipases : Application to
      rootworm sex pheromone synthesis.
AB  - The relative rates of enzyme-catalyzed esterification of the enantiomers of 2
      octanol with various acids were determined for several commercial lipases.
      Interesterifications and hydrolyses of racemic 2-octanol esters catalyzed by
      these enzymes were also examined. Novo'sMucor miehei lipase exhibited
      considerable enantioselectivity and was therefore employed to prepare 8-methyl-2
      decanols with high configurational purity at the carbinol carbon. Esters of these
      alcohols had been previously identified as sexually attractive to several
      rootworm (Diabrotica) species, and the stereochemistry of those esters had been
      shown to be critical to the attraction. The enzymatic resolution provides a
      convenient method to obtain such esters in a desired state of configurational
      purity. 

PMID- 24302149
TI  - Intra- and interspecific chemoattraction studies onSchistosoma mansoni, S.
      japonicum, andS. haematobium in the absence of barriers.
AB  - Heterosexual intra- and interspecific chemoattraction studies were done in
      polycarbonate chambers without barriers using 8- to 10-week-oldSchistosoma
      mansoni from mice, 10-week-oldSchistosoma japonicum from hamsters, and 14-week
      oldSchistosoma haematobium from hamsters. Experiments were done for up to 4 hr at
      37  degrees C in a humidified incubator. Single worms were not attracted to
      decoys or heat-killed worms. Heterosexual intraspecific and interspecific
      attraction was significant at all time points with all combinations. No clear
      differences were apparent between intra- and interspecific attraction.
      Differences between same and differentS. japonicum orS. haematobium pairs were
      not significant at any time point. 

PMID- 24302150
TI  - Technique for injecting intact glands for analysis of sex pheromones of
      Lepidoptera by capillary gas chromatography : Reinvestigation of pheromone
      complex ofMamestra brassicae.
AB  - The structure elucidation of sex pheromones of Lepidoptera by a solid-sample
      injection technique in conjunction with capillary gas chromatography is
      described. The applicability of this method in GC and GC-MS modes was
      demonstrated by reanalyzing the sex attractants of females ofOstrinia nubilalis
      andBombyx mori. The pheromone complex ofMamestra brassicae was reinvestigated and
      (Z)-9-hexadecenyl acetate and (Z)-11-hexadecenol were found in addition to
      already known pheromone components of this species. By using the solid-sample
      injection, the exact site of pheromone release could be determined inM.
      brassicae. 

PMID- 24302151
TI  - Effects of nonhost-plant odors on anemotactic response to host-plant odor in
      female cabbage root fly,Delia radicum, and carrot rust fly,Psila rosae.
AB  - An inflatable polythene wind tunnel was used for behavioral assays of femaleD.
      radicum andP. rosae in diffuse host- and non-host-plant odor, alone and in
      combination. Host-plant odor caused an upwind anemotactic response in both
      species. Changes in fly distribution, relative to wind direction, occurred when
      onion odor was combined with host odor forD. radicum andP. rosae, and when sage
      odor was combined with carrot ordor forP. rosae. The assay has potential for
      screening volatiles for their behavior-modifying effects. 

PMID- 24302152
TI  - Sequence of two genes in pea chloroplast DNA coding for 84 and 82 kD polypeptides
      of the photosystem I complex.
AB  - The genes encoding the two P700 chlorophyll a-apoproteins of the photosystem I
      complex were localized on the pea (Pisum sativum) chloroplast genome. The
      nucleotide sequence of the genes and the flanking regions has been determined.
      The genes are separated by 25 bp and are probably cotranscribed. The 5' terminal
      gene (psaA1) codes for a 761-residue protein (MW 84.1 kD) and the 3' terminal
      gene (psaA2) for a 734-residue protein (MW 82.4 kD). Both proteins are highly
      hydrophobic and contain eleven putative membrane-spanning domains. The homology
      to the corresponding polypeptides from maize are 89% and 95% for psaA1 and psaA2,
      respectively. A putative promoter has been identified for the psaA1 gene, and
      potential ribosome binding sites are present before both genes. 

PMID- 24302154
TI  - The nucleosomal repeat length of pea (Pisum sativum) chromatin changes during
      germination.
AB  - Pea (Pisum sativum) nuclei have been isolated from ungerminated embryos,
      developing embryonic axes and seedlings. Morphological and biochemical criteria
      revealed that preparations were free from contaminants and that nuclei were
      intact. These circumstances permitted an accurate determination of nucleosomal
      repeat lengths, the values obtained being 175+/-4 base pairs for ungerminated
      embryos, 185+/-5 base pairs for 62-hours germinated embryonic axes and 185+/-3
      base pairs for 6-day old seedlings. The results seem to indicate that the
      increase in repeat length is associated with the onset of transcription and/or
      replication of DNA. 

PMID- 24302153
TI  - Two soybean seed lipoxygenase nulls accumulate reduced levels of lipoxygenase
      transcripts.
AB  - Soybean (Glycine max L. [Merrill]) seed lipoxygenase cDNA clones were recovered
      from two cDNA libraries: a size-selected library in pBR322 and an expression
      library in pUC8. The pUC8 library was made with total poly(A)(+) embryo RNA and
      was screened with antiserum to lipoxygenase-1, one of 3 seed lipoxygenase
      isozymes. Three lipoxygenase antigen-producing clones were identified: two with
      identical cDNA inserts of 977 nucleotides representing an open-reading frame and
      a third truncated clone bearing a 3' end common to the longer clones. A long
      clone, pAL-134, was chosen for further study and was used to screen the size
      selected cDNA library from which sixteen clones were identified. They fall into
      two homology classes represented by pLX-10 (ca. 1360 bp) and pLX-65 (2047 bp).The
      lipoxygenase expression clone pAL-134 hybridized much more strongly to pLX-65
      than to pLX-10. pAL-134 and pLX-65 share 89% nucleotide homology and 75% deduced
      amino acid homology along their common sequence. Their deduced amino acid
      sequences each show 80% homology to sequences determined for isolated peptides of
      the lipoxygenase-1 isozyme.pAL-134 hybridizes poorly with a 3.8 kb RNA from LOX-1
      null (lx1) embryos while pLX-65 hybridizes more strongly, but still to a lesser
      extent than its hybridization to standard embryo RNA or to RNA from embryos
      lacking lipoxygenase-2 (lx2) or lipoxygenase-3 (lx3) protein.The lx3 null lacks
      almost all embryo 3.8 kb RNA homologous to pLX-10. This hybridization pattern
      suggests that pLX-10 encodes LOX-3. Thus, the lx1 and lx3 genotypes accumulate
      little, if any, mRNA for the lipoxygenase-1 and lipoxygenase-3 isozymes,
      respectively. 

PMID- 24302155
TI  - Nucleotide sequence of the T-DNA region encoding transcripts 6a and 6b of the
      pTiT37 nopaline Ti plasmid.
AB  - The nucleotide sequence of the T-DNA region encoding transcripts 6a and 6b of the
      pTiT37 nopaline Ti plasmid has been determined. Analysis of this sequence allowed
      us to find two open reading frames in opposite orientation and separated by 482
      bp. Comparison with previous published nucleotide sequences of the homologous
      regions of the pTiAch5 and the pTi15955 octopine Ti plasmids reveals that the
      coding sequences as well as the 5'- and 3' 3-untranslated regions of both genes
      are highly homologous. 

PMID- 24302156
TI  - The transformation of Zea mays seedlings with Agrobacterium tumefaciens.
AB  - Virulent strains of the soil bacterium Agrobacterium tumefaciens infect
      dicotyledonous plants and elicit a profound neoplastic response which results in
      crown gall formation (18). The inciting agent has been shown to be a high
      molecular weight plasmid (Ti) a section of which, the T-DNA, integrates into the
      host plant's genome (4, 28, 30). Although transformation of this kind was
      presumed to be limited to dicots, the detection of enzyme activities linked to
      the expression of T-DNA has been demonstrated in monocots from the families
      Liliaceae and Amaryllidaceae (10, 11).In this communication, we present evidence
      that a member of the commercially important Gramineae also is subject to A.
      tumefaciens directed transformation. This conclusion is based on two
      observations. First, seedlings of Zea mays that have had the bacteria introduced
      into wound sites defined by a region which includes the scutellar node and
      mesocotyl express the activity of enzymes whose synthesis is associated with the
      translation of T-DNA transcripts. Specifically, strain specific lysopine
      dehydrogenase activity has been detected in B6 infected material, whereas
      nopaline dehydrogenase activity is reported only in those plants inoculated with
      C58N. Second, the detection of either of these activities in extracts made from
      infected maize plants requires that the assaulting bacterial strain be competent
      with respect to the transfer of T-DNA. The vir (-) strains, JK195 and 238MX, are
      not, and transformation does not seem to occur. In this connection, the
      corresponding opine synthase activities are not observed. 

PMID- 24302157
TI  - Nodulins and nodulin genes of Glycine max.
AB  - Nodulins are organ-specific plant proteins induced during symbiotic nitrogen
      fixation. Nodulins play both metabolic and structural roles within infected and
      uninfected nodule cells. In soybean, several nodulin genes, coding for abundant
      nodulins, have been identified and isolated. Structural analysis of some of these
      genes has revealed their possible mode of regulation and the subcellar location
      of the protein product. Studies of ineffective symbiosis based on cultivar-strain
      genotype differences suggested that both partners influence the expression of
      nodulin genes. Concomitant with nodule organogenesis, the Rhizobium undergoes
      substantial differentiation leading to the accumulation of nodule-specific
      bacterial proteins, bacteroidins. The major structural alteration occuring in the
      infected cell is the formation of a membrane enclosing the bacteroid
      (peribacteroid membrane). A number of nodulins are specifically targetted to this
      membrane during endosymbiosis. The induction of nodulins and bacteroidins leads
      to the formation of an effective nodule. Nodulin genes can be induced in vitro by
      factors derived from nodules suggesting that trans-activators may be involved in
      derepression of the host genes necessary for Rhizobium-legume symbiosis. 

PMID- 24302158
TI  - Characterization of the spinach chloroplast genes for the S4 ribosomal protein,
      tRNA(Thr) (UGU) and tRNA (Ser) (GGA).
AB  - The map location and nucleotide sequence of the genes for the S4 ribosomal
      protein (rps4) and for tRNA(Thr) (UGU) (trnT) and tRNA(Ser) (GGA) (trnS) on
      spinach chloroplast DNA have been determined. rps4 lies approximately 5 kb 3' to
      atpBE in the large single copy region and is transcribed in the same direction as
      atpBE. It has a 178 bp leader sequence, a 603 bp coding region and 620 bp 3'
      tail. The sequence of the coding region is 83% homologous with that of maize rps4
      (29) and the deduced amino acid sequences from the two species are 7% homologous.
      The spinach and Escherichia coli S4 proteins are only 36% homologous. As in the
      case of maize, trnT lies upstream from and on the same strand as rps4 whereas
      trnS lies downstream and on the opposite strand. Transcription of rps4 apparently
      proceeds past trnS. 

PMID- 24302159
TI  - Specific transcription of a 15-kilodalton zene gene in HeLa cell extracts.
AB  - A maize genomic clone containing a 15 kilodalton zein gene was used as a template
      in an in vitro transcription system for HeLa cells. A runoff assay indicated
      transcription was initiating 5' to the map position of the open reading frame for
      the protein. Fine-structure mapping of RNAs synthesized in vitro showed two
      transcription start sites separated by 24 bases. One start site is 27 bases
      downstream of a consensus TATA sequence; the other is 30 bases downstream of a
      TATG sequences. The initiation sites for RNA synthesized in vitro map to the same
      region of the genomic clone as zein RNA isolated from developing maize kernels. 

PMID- 24302160
TI  - Binge drinking in adolescents: a review of neurophysiological and neuroimaging
      research.
AB  - AIMS: While the relationship between chronic exposure to alcohol and
      neurobiological damage is well established, deleterious brain effects of binge
      drinking in youths have only recently been studied. METHODS: Narrative review of
      studies of brain disturbances associated with binge drinking as assessed by
      neuroimaging (EEG and IRMf techniques in particular) in adolescent drinkers.
      RESULTS: Some major points still deserved to be investigated; directions for
      future research are suggested. CONCLUSIONS: Information and prevention programs
      should emphasize that binge drinking is not just inoffensive social fun, but if
      carried on, may contribute to the onset of cerebral disturbances possibly leading
      to alcohol dependence later in life.

PMID- 24302161
TI  - Association study of common variants within the G protein-coupled receptor kinase
      6 gene and schizophrenia susceptibility in Han Chinese.
AB  - In this study, we examined whether common variants in the G protein-coupled
      receptor kinase 6 gene (GRK6) confers susceptibility to schizophrenia in Chinese.
      We genotyped two common variants in 697 schizophrenia patients and 563 healthy
      control subjects. No significant difference in either allele or genotype
      comparisons between the case and control groups was found. Our results imply that
      GRK6 may not play a role in the pathophysiology of schizophrenia among Han
      Chinese.

PMID- 24302162
TI  - Congenital carotid-jugular fistula in a child: a case report.
AB  - Congenital carotid-jugular (CJ) fistula of the neck is a very rare clinical
      entity that has various causes. The CJ fistulas are particularly prone to
      complications unlike other peripheral arteriovenous fistulas. The aim of this
      report is to present a case of a CJ fistula between the external carotid and the
      external jugular vein, which was successfully closed with detachable balloon by
      an endovascular approach. A 14-year-old child was admitted to our clinic with a
      pulsatile neck swelling. There was no previous history of trauma. A high-flow
      fistula between the external carotid and the external jugular vein was
      determined. The fistula was closed with detachable balloon by an endovascular
      approach. The postoperative angiogram demonstrated complete resolution of the
      fistula. Endovascular treatment of CJ fistulas with detachable balloons is a safe
      and less traumatic technique and may be an effective alternative to the open
      surgery in selected patients. 

PMID- 24302163
TI  - Endovascular repair of popliteal artery pseudoaneurysm with arteriovenous fistula
      after knee arthroscopy: case report and literature review.
AB  - We report a case of postarthroscopic popliteal artery pseudoaneurysm (PSA) with
      arteriovenous fistula (AVF; PSA-AVF) in a 53-year-old woman who presented with
      limb edema, pain, and bruit 1 year after arthroscopic meniscectomy. She was
      treated percutaneously by covered stent deployment. After 6 months of follow-up,
      the patient was asymptomatic, with patency of the stent and occlusion of the AVF.
      A review of the literature was also performed to investigate the prevalence of
      postarthroscopic PSAs and highlight the endovascular approach of treatment.
      Endovascular approach with covered stent appears to be less invasive and might be
      an effective and feasible way of treatment of postarthroscopic popliteal PSA-AVF.

PMID- 24302164
TI  - Percutaneous transcatheter embolization of pulmonary artery pseudoaneurysms
      causing massive hemoptysis: two different case scenarios.
AB  - Systemic bronchial arterial circulation is the most common source for massive
      hemoptysis. Rarely, the source of bleeding can be the pulmonary artery. We report
      2 different case scenarios of massive hemoptysis due to different etiologies, in
      which the source of bleeding was the pulmonary artery. Both the patients were
      treated with percutaneous transcatheter embolotherapy using coils. The 2 cases
      highlight the importance of considering pulmonary arterial etiology as the cause
      of hemoptysis while reporting diagnostic computed tomography studies and
      tailoring the interventional technique toward performing pulmonary angiography
      instead of searching for a systemic arterial source for hemoptysis. 

PMID- 24302165
TI  - Avian, salamander, and forest floor mercury concentrations increase with
      elevation in a terrestrial ecosystem.
AB  - High-elevation ecosystems of the northeastern United States are vulnerable to
      deposition and environmental accumulation of atmospheric pollutants, yet little
      work has been done to assess mercury (Hg) concentrations in organisms occupying
      montane ecosystems. The authors present data on Hg concentrations in ground
      foraging insectivorous songbirds, a terrestrial salamander, and forest floor
      horizons sampled along a forested elevational gradient from 185 m to 1273 m in
      the Catskill Mountains, New York, USA. Mean Hg concentrations in Catharus
      thrushes and the salamander Plethodon cinereus increased with elevation, as did
      Hg concentrations in all forest floor horizons. Mean Hg concentrations in organic
      soils at approximately 1200 m elevation (503.5 +/- 17.7 ng/g, dry wt) were 4.4
      fold greater than those at approximately 200 m. Montane ecosystems of the
      northeastern United States, and probably elsewhere, are exposed to higher levels
      of atmospheric Hg deposition as reflected in accumulation patterns in the forest
      floor and associated high-elevation fauna. This information can be used to
      parameterize and test Hg transport and bioaccumulation models of landscape
      specific patterns and may serve as a monitoring tool for decision makers
      considering future controls on Hg emissions. Further investigation is needed into
      the potential effects of increased Hg concentrations on high-elevation fauna.

PMID- 24302167
TI  - Some forms of love.

PMID- 24302166
TI  - Characterization of one-electron oxidized copper(II)-salophen-type complexes;
      effects of electronic and geometrical structures on reactivities.
AB  - One-electron oxidized salophen-type complexes, [Cu(salophen)](+) (H2salophen =
      N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminobenzene), and its methoxy
      derivatives, [Cu(MeO-salophen)](+) and [Cu(salophen-(MeO)2)](+) (H2MeO-salophen =
      N,N'-bis(3-tert-butyl-5-methoxysalicylidene)-1,2-diaminobenzene, H2salophen
      (MeO)2 = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diamino-4,5
      dimethoxybenzene), have been synthesized and structurally characterized, and
      their reactivities have been investigated. The solid state structures of the one
      electron oxidized forms of these complexes suggested that [Cu(salophen)](+) and
      [Cu(MeO-salophen)](+) can be assigned to relatively localized Cu(ii)-phenoxyl
      radical complexes, while [Cu(salophen-(MeO)2)](+) is the diiminobenzene radical
      complex. On the other hand, [Cu(salophen)](+) in solution showed a different
      electronic structure from that of the solid sample, the radical electron being
      delocalized over the whole pi-conjugated ligand. The reaction of these oxidized
      complexes with benzyl alcohol has been investigated in the presence of a large
      excess of substrate, which revealed the difference in the kinetic behavior
      between the complexes. The mechanisms of the oxidation have been discussed on the
      basis of the electronic and geometrical structures and the reaction kinetics. 

PMID- 24302168
TI  - Factors affecting grief adjustment.
AB  - Earlier research has suggested that therapy and time are factors of change in
      grief level for those who are grieving. This follow-up study of widows and
      widowers suggests that there are also other relevant factors such as church
      activities, death of other relatives, other activities, time of grief counseling
      group, health, age, consideration of remarriage, religion, number of months
      widowed, and financial situation. A regression analysis of 138 widows and
      widowers found each of these factors significantly related to the. 05 critical
      level of significance to various measures of grief level. 

PMID- 24302169
TI  - Inspiration.

PMID- 24302170
TI  - Freud and the fall of man.
AB  - This paper considers the presence in Freud's psychological theories of conceptual
      organizers found in the theory of the Fall of man. The search for such implicit
      and antecedent principles is conducted first in his ontogenetic model and then in
      his model for nosology. A Jungian explanation then follows which proposes that
      the presence of such organizing principles in Freud's ideas is an archetypal
      phenomenon. 

PMID- 24302171
TI  - Spiritual and emotional determinants of health.
AB  - Within our present health care system, there is a growing movement that argues
      that our perceptions of health and illness are in need of change. This change
      includes redefining what we mean by health in terms of the whole person-the
      emotional, social, and spiritual dimensions of our being, as well as the
      physical. An increasing number of health professionals and social scientists
      believe our concepts of health and illness must consider all these aspects of
      life. It is believed that the quality of life may be enhanced by such perceptions
      of health, which include social and spiritual factors. Using data from the 1985
      Akron Area Survey-The Subjective Quality of Life in the Akron Area-this study
      explores the effects of spiritual well-being and emotional well-being on health
      satisfaction. Results indicate that emotional and spiritual factors do
      significantly contribute to the subjective evaluation of health, especially for
      individuals who are physically limited. 

PMID- 24302172
TI  - The nature experiences of a Mississippi watercolorist.
AB  - Watercolorist Walter Anderson, after a series of hospitalizations for mental
      illness, began a series of private journeys to a barrier island off the
      Mississippi coast, where he had a number of ecstatic, mystical experiences vis-a
      vis nature and painted the myriad images he found. It is argued that these
      episodes were not pathological. Anderson's relationships with archetypes and with
      death are presented as central elements of a spiritual journey. 

PMID- 24302175
TI  - The effects of glycyrrhizin on experimental acute pancreatitis in rats.
AB  - INTRODUCTION: Although physiopathology of acute pancreatitis (AP) is not fully
      understood, the roles of reactive oxygen species (ROS) and changes of cytokines
      have been determined. AIM: To investigate anti-inflammatory and anti-oxidant
      effects of glycyrrhizin (GL) on taurocholate-induced AP in rats. MATERIALS AND
      METHODS: Thirty six rats were randomly divided into three groups as sham, AP and
      AP+GL (n=12 per group). AP was induced by 1 ml/kg body weight using 5%
      taurocholate injection into the biliopancreatic duct in groups II and III after
      clamping the hepatic duct. In groups III, GL (20 mg/kg) was given by oral gavage
      twice daily for 4 days. Group I and II did not receive any treatment. After the
      rats were killed; blood samples were taken to measure amylase, lipase, calcium,
      albumin, urea, glucose, AST and LDH assays before killing. Pancreatic tissue
      samples were also taken for biochemical analyses and histopathology. RESULTS:
      Amylase, lipase, AST and urea levels were significantly lower in the AP+GL group
      than in the AP group. Cytokines including IL-6, TNF-alpha and MPO levels were
      significantly lower in the AP+GL group than in the AP group. Even so there is no
      statistically difference between in the AP+GL group and the AP group in terms of
      pancreatic tissue IL-1beta, IL-6 and TNF-alpha levels. DISCUSSION: GL treatment
      significantly decreased pancreatic tissue MPO activities and MDA levels in the
      AP+GL group compared with the other groups (p = 0.001 and p = 0.05,
      respectively). Acinar cell necrosis, hemorrhage, and edema determined that were
      significantly lower in the AP+GL group than in the AP group (p < 0.001).
      CONCLUSIONS: GL treatment for acute necrotizing pancreatitis in rats suppressed
      the levels of pro-inflammatory cytokines, and caused a clear recovery of
      histological changes.

PMID- 24302176
TI  - Neuroprotective effects of carvacrol and pomegranate against methotrexate-induced
      toxicity in rats.
AB  - BACKGROUND: Studies related to the use of various antioxidant and anti
      inflammatory drugs to decrease the toxic side effects related to MTX have been
      carried out. However, since no medicine providing full protection against the
      side effects of MTX has been discovered, the discovery of new agents is required.
      AIM: The aim of this study was to determine whether methotrexate (MTX) causes
      oxidative stress and an inflammatory response in sciatic nerve, as well as
      whether carvacrol (CAR) and pomegranate (POM) have protective effects against the
      resulting oxidative stress and inflammatory response. MATERIALS AND METHODS: 32
      adult male Wistar albino rats were used in the study. The animals were divided
      into 4 groups: Group C: the rats were not given any medication; Group MTX: On
      study day 2, the rats were given a single dose of 20 mg/kg MTX, administered
      intraperitoneally; Group MTX+CAR: On study day one, the rats were administered a
      single dose of 73 mg/kg CAR intraperitoneally. On study day two, a single dose of
      20 mg/kg MTX was administered intraperitoneally; Group MTX+POM: For seven days
      starting from the study day one, rats were given 225 mg/kg POM extract once a day
      through orogastric gavage. On study day two, a single dose of 20 mg/kg MTX was
      administered intraperitoneally. All animals were sacrificed on the day eight.
      TOS, TAS, MDA, TNF-alpha and IL-1beta levels were evaluated in the sciatic nerve
      tissue. RESULTS: In comparison to the control group, a decrease in TAS levels and
      an increase in TOS, MDA, IL-1beta and TNF-alpha levels were detected in the MTX
      group. Compared to the MTX group, the MTX+CAR group had a significant increase in
      TAS level and significant decreases in TOS, MDA, IL-1beta and TNF-alpha levels.
      In comparison to the MTX group, the MTX+POM group had a significant decrease in
      MDA, IL-1beta and TNF-alpha levels. When the MTX+CAR and MTX+POM groups were
      compared, the TNF-alpha level measured was lower in the MTX+CAR group.
      CONCLUSIONS: In this work, we have shown that MTX causes a significant oxidative
      stress and inflammatory response in rats' sciatic nerve tissue and that CAR had
      an antioxidant effect in this system. Furthermore, we have proven, for the first
      time, that both CAR and POM decreased the pro-inflammatory response.

PMID- 24302177
TI  - Screening of feature genes of the renal cell carcinoma with DNA microarray.
AB  - AIM: To investigate the underlying molecular mechanisms of renal cell carcinoma
      (RCC) by using the microarray expression profiles of normal kidney and RCC tissue
      for early diagnosis and treatment of RCC. MATERIALS AND METHODS: The gene
      expression profile of GES781 was downloaded from Gene Expression Omnibus
      database, including including nine tissue samples of RCC tissues removed from
      nine patients and eight adjacent normal renal tissue samples. We identified the
      differentially expressed genes (DEGs) by Multtest package in R software. The
      screened DEGs were further analyzed by bioinformatics methods. Firstly, the
      comparison of the DEGs expression degree was performed by cluster analysis.
      Secondly, DAVID was used to perform functional analysis of up- and down-
      regulated genes and the protein-protein interaction (PPI) networks were
      constructed by prePPI. Finally, the pathways of genes in PPI networks were
      discovered by WebGestalt. RESULTS: Compared with the control, we screened 648
      down-regulated and 681 up-regulated DEGs. And the down- and up-regulated DEGs
      with maximum expression degree were UMOD (uromodulin) and FABP7 (fatty acid
      binding protein 7), respectively. There was significant difference in the gene
      expression between the normal kidney and RCC tissue. The up-regulated DEGs in RCC
      tissue were significantly related to the immune responses and the down-regulated
      DEGs were significantly related to the oxidation reduction. The most significant
      pathway in the PPI network of UMOD was cytokine-cytokine receptor interaction.
      CONCLUSIONS: The screened DEGs have the potential to become candidate target
      molecules to monitor, diagnose and treat the RCC, and might be beneficial for the
      early diagnosis and medication control of RCC.

PMID- 24302178
TI  - Suppression of RNA interference on expression of c-myc of SKOV3 ovarian carcinoma
      cell line.
AB  - AIM: To investigate suppression of RNA interference (RNAi) on expression of c-myc
      of SKOV3 ovarian carcinoma cell line. MATERIALS AND METHODS: The c-myc -siRNA was
      designed and synthesized, then transfected to SKOV3 ovarian carcinoma cell lines.
      The cell lines were divided into four groups, including the blank control group,
      the siRNA transfection group, the mock transfection group and the negative
      control group. The expression level of c-myc mRNA and protein were detected by RT
      PCR and Western blotting, respectively. The growth and proliferation of SKOV3
      ovarian carcinoma cell lines were observed with CCK-8 assay. RESULTS: After
      transfected with c-myc -siRNA, the expression level of c-myc mRNA and protein
      were down-regulated, the growth and proliferation of SKOV3 ovarian carcinoma cell
      line were inhibited in the siRNA transfection group. There were significant
      differences between the siRNA transfection group and the blank control group (p <
      0.05). The silencing efficiency was 77.78%, the protein suppression rate was
      67.78%, and the inhibition ratio was 56.35% by CCK-8 assay in siRNA transfection
      group. CONCLUSIONS: The down-regulation of c-myc expression of SKOV3 ovarian
      carcinoma cell line by c-myc -siRNA can lead to the suppression of cancer cell
      proliferation. The small interfering RNAs technique can inhibit the proliferation
      of carcinoma cell by oncogene silencing.

PMID- 24302179
TI  - Different Expression of p16INK4a and p14ARF in cervical and lung cancers.
AB  - AIM: This study aimed to assess clinical significance of expression of p16INK4a
      and p14ARF proteins in cervical and lung cancers. MATERIALS AND METHODS:
      Expression of these proteins was examined in 50 cervical cancer specimens (42 hr
      HPV-associated cervical cancer and 8 non-hr-HPV-associated cervical cancer) and
      127 lung cancer specimens (34 squamous cell carcinomas, 33 adenocarcinomas, 36
      bronchioloalveolar carcinomas, and 24 small cell lung cancers) by
      immunohistochemistry. RESULTS: Overexpression of both p16INK4a and p14ARF was
      found in 100% cervical cancer specimens and in, respectively, 61.42% and 30.79%
      of lung cancer specimens. Thus, expression ratio of p16INK4a and p14ARF was
      significantly higher in cervical cancer than in lung cancer (p < 0.01). Both
      proteins were unexpressed in 38 lung cancer specimens (29.92%), and there was no
      correlation between the expressions of these proteins. CONCLUSIONS: Different
      patterns of p16INK4a and p14ARF expression in cervical and lung cancer patients
      suggest different involvement of these proteins in the development of either
      cancer type. We propose p16INK4a and p14ARF as biomarkers in clinical assessment
      for cervical cancer.

PMID- 24302180
TI  - Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a
      bivariate meta-analysis.
AB  - OBJECTIVES: The diagnosis of lung cancer remains a clinical challenge. Many
      studies have assessed the diagnostic potential of anti-p53 antibody in lung
      cancer patients but with controversial results. This study aims to summarize the
      overall diagnostic performance of anti-p53 antibody in lung cancer. MATERIALS AND
      METHODS: Based on a comprehensive search of the Pubmed and Embase, we identified
      outcome data from all articles estimating diagnostic accuracy of anti-p53
      antibody for lung cancer. 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. RESULTS: According to our
      inclusion criteria, 16 studies with 4414 subjects (2249 lung cancers, 2165
      controls) were included. The summary estimates were: sensitivity 0.20 (95% CI
      0.15-0.27), specificity 0.97 (95% CI 0.95-0.98), positive likelihood ratio 6.64
      (95% CI 4.34-10.17), negative likelihood ratio 0.83 (95% CI 0.77-0.89),
      diagnostic odds ratio 8.04 (95% CI 5.05-12.79), the AUC was 0.84. Subgroup
      analysis suggested that anti-p53 antibody had a better diagnostic performance for
      small cell lung cancer than non-small cell lung cancer. CONCLUSIONS: anti-p53
      antibody can be an assistant marker in diagnosing lung cancer, but the low
      sensitivity limits its use as a screening tool for lung cancer. Further studies
      should be performed to confirm our findings.

PMID- 24302181
TI  - Comparison of the effects of dexmedetomidine and remiphentanyl on emergence
      agitation after sevoflurane anesthesia in adults undergoing septoplasty
      operation: a randomized double-blind trial.
AB  - OBJECTIVES: Sevoflurane is an ideal agent for anesthesia since its respiratory
      irritant effect is minimal during mask induction. Emergence agitation (EA) is a
      common problem after anesthesia with sevoflurane. In this study it was aimed to
      compare the effects of dexmedetomidine and remifentanyl on emergence agitation
      after sevoflurane anesthesia in adults undergoing septoplasty operation. PATIENTS
      AND METHODS: This prospective, randomized, double-blind study was conducted in
      Yenimahalle State Hospital after obtaining local Ethics Committee approval and
      patient's written informed consent. The patients were randomized into
      dexmedetomidine and remifentanyl groups. Hemodynamic parameters including heart
      rat, Mean arterial pressure, and sPO2 were recorded. The patients were followed
      for 1 hour at the recovery room. Categorical data was analyzed using c2 test.
      Hemodynamic data was evaluated using unpaired t test for intergroup and paired t
      test for within group comparisons. Data not normally distributed was compared
      using Mann Whitney U test. p < 0.05 was considered statistically significant.
      RESULTS: Demographic data were similar in both groups (p > 0.05). Riker score was
      similar in both groups. VAS score was also not significantly different between
      both groups at the recovery room. CONCLUSIONS: Our study demonstrated that
      Dexmedotimidine and Remifentanyl had equal effectiveness in reducing emergence
      agitation in patients undergoing septoplasty under Sevoflurane anesthesia.

PMID- 24302182
TI  - Thyroid autoimmunity in patients with Familial Mediterranean Fever: preliminary
      results.
AB  - AIM: We investigated whether there was a significant increase in thyroid
      autoimmunity in patients with Familial Mediterranean fever (FMF). PATIENTS AND
      METHODS: In total, 220 patients, consisting of 42 with FMF, 75 with rheumatoid
      arthritis (RA), and 103 healthy controls, were enrolled. Serum thyroid
      stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and
      thyroid autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin) were
      measured in all participants. RESULTS: After adjustment for age, gender, and
      smoking status, statistically significant differences between serum levels of
      anti-thyroglobulin antibody, anti-thyroid peroxidase antibody, and fT3 were found
      between the groups (all p < 0.001). Serum TSH level did not differ between the
      groups (p > 0.05). The frequency of autoimmune thyroiditis in FMF group is higher
      than control group. However, this difference did not reached the level of
      statistical significance (p > 0.05). CONCLUSIONS: Although statistically not
      significant, thyroid autoimmunity was observed more frequently in patients with
      FMF than in healthy controls. Thyroid autoantibodies were significantly higher in
      patients with FMF. Studies with greater number of patients are required for
      evaluating the frequency of the autoimmune thyroiditis in patients with FMF.

PMID- 24302183
TI  - 5 to 8 years follow-up of knee chondral defects treated by PVA-H hydrogel
      implants.
AB  - AIM: Despite the various treatment options available, symptomatic articular
      cartilage defects continue to represent a therapeutic challenge for knee
      surgeons. This study has been developed in order to retrospectively evaluate and
      present long term results, from 5 to 8 years, of PVA-H hydrogel impants
      ("Cartiva") in the treatment of knee chondral focal defects. PATIENTS AND
      METHODS: Presented are the clinical and MRI evaluation of 18 patients with III
      and IV degree knee chondral or osteochodral defects treated by PVA-H hydrogel
      implants. Defects were no larger than 20 mm in diameter. Average age at time of
      surgery was 54 years. There were 11 male and 7 female patients. A total of 20
      implants were implanted, 16 with 10 mm and 4 with 15 mm Cartiva implants. One
      patient was treated bilaterally. The majority (80%) of surgeries were performed
      arthroscopically. Patients have been assessed by IKDC, SF36 scores and by MRI
      imaging. RESULTS: All patients have shown improvement of knee function and knee
      scores, in many cases over 50 points of IKDC, except three. Of these, the first
      mantained a rather good quality of life for over 5 years with approximately the
      same level of functionality she enjoys now, after implant removal and knee
      replacement during 2008. The second case was a 43 year old female with a post
      traumatic chondral defect in a valgus knee. The patient experienced post-op pain:
      the implant was removed among another institution at 6 months post-op and was
      converted to OATS. The third case was a 49 year old male with a severe arthritic
      pre-op knee and may not have been ideal candidate for Cartiva, but was too young
      for a total knee replacement at the time of operation and, despite a severe knee
      worsening during the last year that will need in the short future a knee
      replacement, has, at over 6 years follow-up, an IKDC score of 33.33 from a pre-op
      of 37.93. CONCLUSIONS: 5 to 8 yy follow-ups enable us to conclude that the use of
      PVA-H synthetic implants in knee chondral defects in middle aged patients can
      guarantee critical knee function improvement and severe pain reduction. Even the
      patients, that have needed a knee replacement, have well done for the first four
      five years. Therefore, this mean that this type of treatment with the correct
      indications and future implant and instrumentation improvements, already in
      course, may guarantee a several year period of knee health and active life style.

PMID- 24302184
TI  - The evaluation of Lugol's iodine solution staining combined with endoscope for
      diagnosis of non-erosive reflux disease in clinic.
AB  - AIM: To evaluate the value of Lugol's iodine solution staining combined with
      endoscope on the diagnosis of non-erosive reflux disease (NERD). PATIENTS AND
      METHODS: A total of 96 gastroesophageal reflux disease patients were selected to
      participate in this study. The patients were stained on esophageal mucosa by
      Lugol's iodine solution and examined at routine endoscopy. The shallow staining
      and/or non-staining group patients were treated with esomeprazole and mosapride
      citrate, and then the changes in Lugol's iodine staining, Gerd Q (Gerd
      questionnaire) scoring and histological characters of esophageal mucosa were
      recorded before and after treatment. RESULTS: As the results, a total of 68
      patients were diagnosed as NERD, and 36 of 68 patients were observed with uniform
      staining and 32 of 68 patients were observed with shallow staining and/or non
      staining. After 4 weeks for treatment, 28 of 32 patients with shallow staining
      and/or non-staining became uniform staining and 4 of 32 patients were still with
      shallow staining and/or non-staining. Before and after treatment, the Gerd Q
      scoring of uniform staining groups and shallow staining and/or non-staining
      groups all had a significant difference (p < 0.05). Compared to the routine
      endoscopy, the detection rate of abnormal esophageal mucosa was significantly
      increased by Lugol's iodine solution staining combined with endoscope.
      CONCLUSIONS: Lugol's iodine solution staining combined with routine endoscopy,
      Gerd Q scoring and histomorphology can be used to evaluate the diagnosis and
      therapeutic effect of NERD.

PMID- 24302185
TI  - A clinical prediction model and its application for bleeding in chronic liver
      failure patients with esophageal varices.
AB  - OBJECTIVES: We aimed to explore the model for end-stage liver disease (MELD),
      Child-Turcotte-Pugh (CTP) score, endotoxin, bleeding score and dynamic changes of
      D-dimer in chronic liver failure patients with portal hypertension and esophageal
      varices, and explored their potential contact with bleeding in short-term
      prognosis. PATIENTS AND METHODS: Chronic liver failure patients with esophageal
      varices were divided into 2 groups: bleeding group (Group A, n=50) and non
      bleeding group (Group B, n=50). MELD, CTP score, endotoxin and plasma D-dimer was
      compared at different time point. The receiver operating characteristic curve
      (ROC) was drawn. The predictive model based on their cut off value in esophageal
      varices bleeding patients was evaluated. RESULTS: Infection and endotoxin levels
      were related with bleeding and death in chronic liver failure patients with
      esophageal varices, and affect the patient's coagulation and fibrinolysis
      activity. The criteria of predictive model for predicting hemorrhage of
      esophageal varices in patients with chronic liver failure is: MELD >= 26;
      bleeding grading score >= 10; and/or plasma D-dimer > 700 ug/L. Plasma D-dimer,
      MELD score and death rate showed significant differences between two groups.
      Patients with chronic liver failure occurred bleeding and eventually dead have
      persistent anomaly plasma D-dimer level. In our model-group patients, the D-dimer
      and CTP score has statistical difference between surviving and death patients (p
      < 0.05). CONCLUSIONS: This model could predict the prognosis of bleeding in
      chronic liver failure patients with esophageal varices. And has the short-term
      prognostic value for clinical application.

PMID- 24302186
TI  - Phenylketonuria is not a risk factor for gut mucosa inflammation: a preliminary
      observation.
AB  - BACKGROUND: Phenylketonuria (PKU) is an inborn error of amino acid metabolism in
      which high phenylalanine (Phe) concentrations in the central nervous system
      adversely affect its development and functioning. In PKU high oxidative stress
      and inefficiency of free radical scavenging may lead to systemic chronic
      inflammation. We hypothesised that in PKU gut mucosa is chronically inflamed and
      that this leads to release of calprotectin from neutrophils and monocytes. AIM:
      The aim of this study was to compare intestinal mucosa inflammation status, as
      measured using fecal calprotectin, in patients with PKU irrespective of
      compliance, and healthy controls. PATIENTS AND METHODS: Forty-four patients with
      classical PKU were included in the study (21 male, 23 female; aged 0-41 years;
      mean +/- SEM: 16.5 +/- 1.7 years). Forty-eight healthy subjects (HS) aged 9-68
      years (29.4 +/- 2.6 years) comprised the control group, of whom 21 were male and
      27 female. Among PKU patients 25 had normal Phe blood concentrations and in 19
      they were elevated. In all subjects calprotectin stool concentrations were
      assessed (PhiCal ELISA, Calpro, Lysaker, Norway). RESULTS: Normal FC (fecal
      calprotectin) concentrations were found in 43 (97.7%) PKU patients and 46 (95.8%)
      HS. No correlation between dietary control of Phe blood concentrations and FC
      levels in PKU patients was found. CONCLUSIONS: No detectable intestinal
      inflammation occurs in phenylketonuria. Lack of dietary control and elevated Phe
      levels do not seem to be risk factors for inflammation of the mucosa of the gut.

PMID- 24302187
TI  - The inhibitory effect of melatonin on colonic motility disorders induced by water
      avoidance stress in rats.
AB  - OBJECTIVES: Psychological stress is involved in the etiology of functional
      gastrointestinal disease (FGID). Accumulations of chronic continuous stress
      associate with the symptoms of the gastrointestinal tract (GIT) including
      abdominal discomfort, pain, constipation or diarrhea. Melatonin (MT) is a
      neurohormone which mainly synthesized in the pineal gland and GIT, has been shown
      to alleviate the stress and regulate the intestinal motility. Although melatonin
      attenuated abnormal defecation induced by stress, the mechanisms of the effect
      are not fully elucidated. This study sought to investigate the effect of
      melatonin (MT) on colonic smooth muscle contractility disorders induced by
      chronic water avoidance stress (WAS). MATERIALS AND METHODS: 36 adult Wistar rats
      were divided into three groups [Control+V (vehicle solution), WAS+V, WAS+MT]. The
      WAS+V and WAS+MT groups were suffered from WAS for one hour daily for 10 days.
      Melatonin was given 30 min before stress session in the WAS+MT group. Colonic
      motility was assessed using the numbers of fecal pellet output. The
      concentrations of melatonin and serotonin (5-HT) were measured through ELISA
      method. The contractions of isolated colonic strips were assessed through
      isometric force transducer. RESULTS: The numbers of fecal output was increased in
      the WAS+V group, and melatonin attenuates the increased fecal pellet output
      induced by WAS. The concentrations of 5-HT was increased by WAS, and melatonin
      decreased the augment in the concentration of 5-HT. In the part of contraction
      recording of colonic smooth muscle, melatonin inhibited the fortified spontaneous
      contraction induced by WAS, and decreased the amplitude of spontaneous
      contraction stimulated by Ach and KCl after WAS treatment. CONCLUSIONS: Melatonin
      could inhibit WAS-induced fecal output pellets by inactivating the 5-HT pathway,
      may interact with calcium channel and inhibit the influx of calcium.

PMID- 24302188
TI  - Fluticasone nasal spray as an adjunct to Amoxicillin for acute sinusitis in
      children: a randomized controlled trial.
AB  - BACKGROUND: Approximately 0.5-2% of upper respiratory tract infections in adults
      and 6-13% of viral upper respiratory tract infections in children are complicated
      by acute sinusitis. This study was aimed to evaluate the coadministration effect
      of fluticasone nasal spray (FNS) with amoxicillin for AS in children. MATERIALS
      AND METHODS: One hundred children 2 to 14 years of age with acute sinusitis
      referred to Shahid Mohammadi Pediatric Hospital in Bandar Abbas were randomly
      allocated into two equal intervention and control groups to receive amoxicillin
      with fluticasone nasal spray one puff twice daily for 14 days and amoxicillin 80
      to 100 mg/kg/ day for 14 days respectively. RESULTS: Twenty one (42%) of children
      in intervention group were cured completely and 2 (4%) children in control group
      had complete recovery (p < 0.001). Symptom severity score was 22.98 +/- 2.95
      before treatment that reduced to 13.26 +/- 3.20 after treatment (p < 0.001).
      CONCLUSIONS: Use of fluticasone can reduce the severity of symptoms of sinusitis
      in children.

PMID- 24302189
TI  - KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation.
AB  - OBJECTIVES: KL-6 is a pulmonary epithelial-derived mucin which is secreted mainly
      by type II alveolar epithelial cells. The level of KL-6 in serum is closely
      correlated to the clinical activity of various interstitial lung diseases (ILD)
      and acts as a prognostic factor for ILD patients. Previous studies have showed
      that KL-6 promoted chemotaxis, proliferation and inhibited the apoptosis of human
      lung fibroblasts. However, the underlying mechanism remains unknown. In this
      study, we investigated the function of KL-6 on the expression of hepatocyte
      growth factor (HGF), transforming growth factor-beta1 (TGF-beta1), collagen and
      alpha-smooth muscle actin(alpha-SMA) in human embryonic lung fibroblasts cell
      line MRC-5. METHODS: Human embryonic lung fibroblasts were cultured in Eagle's
      minimum essential medium. The cells plated in 6-well plates was cultured in serum
      free medium at 37 degrees C in 5% CO2 and challenged with recombinant KL-6 at a
      final concentration of 0, 10, 20, 40 ng/mL. Five micrograms of total RNA template
      were transcripted to cDNA by using AMV (Avian Myeloblastosis Virus) reverse
      transcriptase and random 9 mers as the first-strand primer. Synthesized cDNA was
      used in PCR experiments. The expression of TGF-beta1 and HGF in cell culture
      supernatants was measured using ELISA kit. Cells incubated with KL-6 for 72h were
      collected for flow-cytometry analysis. The analysis was done using a Beckman
      counter device. RESULTS: It was found that KL-6 up-regulated the expression of
      collagen type I and III in a dose-dependent manner. However, the addition of KL-6
      significantly inhibited the production of HGF. As regard to the biological
      function, KL-6 induced myofibroblast differentiation confirmed by the elevated
      expression of a-SMA. CONCLUSIONS: KL-6 is one of the key molecules involved in
      epithelial-mesenchymal interactions and might contribute to the fibrosis in ILD.

PMID- 24302190
TI  - FeNO levels in children with asthma and other diseases of the lung.
AB  - BACKGROUND: Prolonged cough in children is one of the major complaints seen in
      hospitals. It is difficult to make a proper diagnosis and start the appropriate
      treatment. Fraction of exhaled nitric oxide (FeNO) measurement is a valuable non
      invasive diagnostic tool in determining the cause of prolonged cough in children.
      Although there are several studies on asthma and COPD, there is a lack of them on
      other lung diseases such as tuberculosis, bronchiectasia, bronchiolitis
      obliterans (BO), and pneumonia. PATIENTS AND METHODS: In this study, pre
      treatment FeNO levels of patients with various lung diseases were measured and
      results from the sick patient groups were compared with the results from the
      control group. RESULTS: Pre-treatment FeNO levels in BO, asthma, and tuberculosis
      patient groups were higher than in the control group (p < 0.001). There was no
      significant difference between the acute bacterial pneumonia and bronchiectasia
      groups, and the control group (p > 0.05). CONCLUSIONS: FeNO measurement is a
      highly important guiding tool in diagnosis and treatment of various lung
      diseases.

PMID- 24302191
TI  - Screening for preeclampsia pathogenesis related genes.
AB  - OBJECTIVES: Preeclampsia is a complication of pregnancy that severely threatens
      the health of the mother and infant, yet the mechanism of pathogenesis remains
      unclear. In this article, gene array technology was applied to identify the genes
      related to the pathogenesis of preeclampsia, and to explore the regulatory effect
      of epigenetic modification by on these genes. PATIENTS AND METHODS: Placental
      tissue of preeclampsia patients was collected, and DNA methylation arrays and
      gene expression microarrays were used to identify the genes. The effect of
      methylation on the regulation of genes related to the pathogenesis of
      preeclampsia was also investigated. RESULTS: The expression levels of more than
      ten genes were found to be significantly altered in the placental tissue of
      patients with preeclampsia as measured by gene expression microarray. This study
      also identified more than ten genes with notable changes in expression level as
      well as methylation level. The gene expression of CUEDC1 and DHX34 were verified
      in this study and the findings were consistent with previous reports.
      CONCLUSIONS: Our research indicates that the occurrence of preeclampsia is
      correlates closely with differences in the expression of specific genes, which
      may be regulated through methylation.

PMID- 24302192
TI  - Inositol: effects on oocyte quality in patients undergoing ICSI. An open study.
AB  - OBJECTIVES: Nuclear and cytoplasmic competence of human oocyte is critical for
      future competence of the embryo upon which ultimately depends the outcome of an
      ART (Assisted Reproductive Technology) treatment. Follicular microenvironment in
      which the oocyte develops is crucial, and this must be taken into account
      particularly with the use of hormonal ovarian stimulation protocols. Inositol is
      an important element of the follicular environment and data support that its
      higher level in follicular fluid correlates with the development of a good
      oocyte. Aim of this study is to understand the effects of treatment with inositol
      on oocyte quality in a sample of patients undergoing ICSI (Intracytoplasmic Sperm
      Injection). PATIENTS AND METHODS: Assessment of oocyte/embryo quality and
      pregnancy rates in 149 patients divided, according to a controlled randomized
      pattern, into two groups: study group 1 treated with folic acid and inositol and
      control group 2 treated with folic acid alone. RESULTS: The number of patients
      with excellent and good oocyte quality appears to be significantly higher in
      group 1 (p = 0.02), as shown, they significantly increased the number of embryos
      of grade A transferred in the group 1 (p = 0.02) compared to group 2, despite
      being completely similar averages of total embryos transferred (total mean +/- SD
      = 2.4 +/- 0.8, group 1 mean +/- SD = 2.4 +/- 0.8, group 2 mean +/- SD = 2.4 +/-
      0.8). There is not any significant difference between groups 1 and 2 in the
      number of positivity to beta-hCG and in the number of biochemical pregnancies
      detected although it has a tendency to increase in the first and to decrease in
      the second for group 1. The increase in percentage of clinical pregnancies in
      group 1 was statistically significant (p = 0.02), whereas there was no apparent
      significance in the difference between the biochemical and clinical pregnancies
      in the two groups despite the positive trend in the study group. CONCLUSIONS:
      Relying on "inositol help" to solidify our efforts, seems to be an easy path to
      help to deepen the effectiveness of its use in all patients still under 40 but
      with prior failed attempts at ICSI or diagnosed with PCOS or as "poor
      responders".

PMID- 24302193
TI  - Immunohistochemical and ultrastructural changes in rat fat tissue related to the
      local hCG injection.
AB  - OBJECTIVES: Recently, it has been observed that weight loss is accelerated by
      human chorionic gonadotropin (hCG) hormone preparation used for hypothalamic
      dysfunction in obesity treatment in both sexes. hCG is also used for in vitro
      fertilization and in treatment of hypogonadotropic hypogonadism. Our aim was to
      observe the ultrastructural changes caused by local injections of hCG made for
      purpose of weight loss and to present them to inform those receiving such
      therapy. MATERIALS AND METHODS: In our study, 10 obese female, 10 male obese, 10
      non-obese female and 10 non-obese male rats were used. In each group, single dose
      of subcutaneous hCG injection has been applied to 7 rats for 5 weeks in 5 days of
      the week, and placebo has been applied to the remaining 3 rats. Following the
      injection, the tissues were evaluated morphologically, immunohistochemically and
      ultrastructurally. RESULTS: Leptin immunoreactivity was similar in all groups.
      When the adipose tissue samples were examined under electron microscope, they
      were observed to exhibit normal structure with organelles located around the
      nuclei and nucleoli, and no distinctive features were found among the groups.
      CONCLUSIONS: Administering hCG in addition to diet had no advantage on weight
      reduction in rats.

PMID- 24302194
TI  - A novel germline mutation of the MEN1 gene caused multiple endocrine neoplasia
      type 1 in a Chinese young man and 1 year follow-up.
AB  - BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant
      cancer predisposition syndrome which manifests a variety of endocrine and non
      endocrine neoplasms and lesions. Because of its complexity in clinical
      manifestations, it is always difficult to set up the diagnosis in the early stage
      of the disease. AIM: Using genetic diagnosis to identify and describe the process
      of the disease from the very beginning and followed the treatment result in 1
      year. MATERIALS AND METHODS: In this assay, a Chinese young man aged 31 with
      parathyroid hyperplasia, suspected gastrinoma and an enlarged pituitary with
      elevated level of prolactin (PRL) and growth hormone (GH) was admitted to our
      Department ward. We performed genetic analysis in his family and described a new
      nonsense mutation at codon 308 in exon 6 of the MEN1 gene, where a cytosine
      residue was exchanged for guanine residue (TCA > TGA), and a termination condon
      (S308X) occurred. During the 1 year follow up, typical manifestations emerged in
      this kindred and further confirmed the diagnosis of familial MEN 1. CONCLUSIONS:
      We presented a case of MEN 1 from its early stage and followed the progression.
      Meanwhile, the mutation in this kindred has not been reported and our finding can
      contribute to better understanding about this disease.

PMID- 24302195
TI  - Recurrence of tako-tsubo syndrome, idiopathic dilated cardiomyopathy, and
      iterative ventricular tachycardia: just a fortuitous coincidence or a
      pathophysiological link?
AB  - We report the case of a 65-year-old woman with late recurrence of tako-tsubo
      syndrome, idiopathic dilated cardiomyopathy and prior iterative ventricular
      tachycardia. We hypothesize that the pathophysiological link among these clinical
      conditions could be the hyperactivity of the sympathetic nervous system. 

PMID- 24302196
TI  - Mean platelet volume in patients with ischemic stroke.

PMID- 24302197
TI  - Vancomycin: over 50 years later and still a work in progress.

PMID- 24302198
TI  - Pig fat, pork bellies, and portly appearance.

PMID- 24302199
TI  - New faster CHARMM molecular dynamics engine.
AB  - We introduce a new faster molecular dynamics (MD) engine into the CHARMM software
      package. The new MD engine is faster both in serial (i.e., single CPU core) and
      parallel execution. Serial performance is approximately two times higher than in
      the previous version of CHARMM. The newly programmed parallelization method
      allows the MD engine to parallelize up to hundreds of CPU cores.

PMID- 24302200
TI  - Energetics of the response of maize coleoptile tissue to indoleacetic acid :
      Characterization by flow calorimetry as a function of time, IAA concentration,
      and pH.
AB  - Indole-3-acetic acid (IAA) promotes an increase in steady-state heat production
      by corn (Zea mays L.) coleoptile tissue; this increase is associated with an
      elevation in aerobic respiration rates. A detailed time dependence of the
      exothermic response to IAA was obtained using flow calorimetry. The latent period
      and magnitude of response were evaluated as a function of IAA concentration and
      pH. The data indicate that more than one response may occur. The optimal change
      in heat production was produced by an IAA concentration of 3.10(-5) M. It was
      initiated within 5 min after the start of the IAA treatment, and reached a
      magnitude in excess of 25% of the tissue's basal heat production. Concentrations
      of IAA greater than 1.10(-4) M resulted in diminished response(s), but the effect
      was strongly pH dependent. Several possibilities for the increased heat
      production triggered by IAA are discussed. 

PMID- 24302201
TI  - A possible plasma membrane particle containing malic enzyme activity.
AB  - A definite membrane fraction from Cucurbita hypocotyls, maize coleoptiles, and
      other plant tissues contains a NADP-dependent malic enzyme activity, up to 10% of
      overall tissue activity, and probably other soluble proteins. This "malic enzyme
      particle" is identified as plasmalemma on the basis of sedimentation behavior,
      density distribution in sucrose gradients, in comparison with enzyme markers, and
      sluggish penetration by the sugar Metrizamide. Enzyme binding to the plasma
      membrane is stable and scarcely sensitive to salts and EDTA, although all
      activity is released to the supernatant in the presence of Triton-X-100 or under
      hypotonic conditions. The properties of bound enzyme are similar to those of free
      enzyme in cell extracts. It is proposed that osmotically sensitive plasma
      membrane vesicles, containing cytoplasm fragments, are formed during
      homogenization. Low malic enzyme activities are also associated with Cucurbita
      proplastids. 

PMID- 24302202
TI  - Ultrastructural organization of chloroplast membranes in mutants of Pisum sativum
      L. with impaired activity in the photosystems.
AB  - The ultrastructural organization and the photosynthesis reactions of chloroplast
      membranes were studied in three lethal mutants of Pisum sativum, Chl-1, Chl-19
      and Chl-5, all lacking the capacity to evolve oxygen. The rates of 2,6
      dichloroindophenol reduction, delayed fluorescence and electron-spin-resonance
      signal 1 indicate that Chl-1 and Chl-19 have an impaired activity in photosystem
      II (PS II), while in Chl-5 the electron transport is blocked between PS I and the
      reactions of CO2 fixation. Ultrathin sectioning demonstrates the presence of
      giant grana in the chloroplasts of Chl-1 and Chl-19, while the chloroplast
      structure of the Chl-5 is very similar to that of the wild-type. The grana of the
      Chl-19 mutant contain large multilamellar regions of tightly packed membranes.
      When the chloroplast membranes were studied by freeze-fracture, the exoplasmic
      and protoplasmic fracture faces (EF and PF, respectively) in both stacked and
      unstacked membranes were found to show large differences in particle
      concentrations and relative population area (per MUm(2)), and also in particle
      size distribution, between all mutant chloroplast membranes and the wild-type. A
      close correlation between increasing kmt (ratio of particle concentrations on
      PF/EF) and PS II activity was observed. The differences in particle
      concentrations on both fracture faces in different regions of the intact
      chloroplast membranes of the wild-type are the consequence of a rearrangement of
      existing membrane components by lateral particle movements since quantitative
      measurements demonstrate almost complete conservation of intramembrane particles
      in number and size during the stacking of stroma thylakoid membranes. The results
      indicating particle movements strongly support the concept that the chloroplast
      membranes have a highly dynamic structure. 

PMID- 24302203
TI  - Growth and sesquiterpenoid production by Calypogeia granulata inoue cells in
      suspension culture.
AB  - Growth and the production of volatile sesquiterpenoids by a chlorophyllous cell
      suspension culture from gametophytes of C. granulata, a leafy liverwort, were
      examined. Glucose was more effective than 2,4-dichlorophenoxyacetic acid for
      callus induction, and elimination of glucose from the medium resulted in prompt
      redifferentiation of plantlets. The cells grew photoheterotrophically, but not in
      the dark. 1,4-Dimethylazulene, a trinorsesquiterpenoid, was produced as the major
      volatile sesquiterpenoid in the cultured cells; bicyclogermacrene, compound II,
      an indene-type aldehyde (a trinorsesquiterpenoid aldehyde), compound I and
      tetrahydro-1,4-dimethylazulene (a trinorsesquiterpenoid) followed in decreasing
      order. The azulene was produced both in light and the dark, and its yield was
      proportional to the growth in light. The yield in light was four times higher
      than that in the dark. The content of 1,4-dimethylazulene was 0.9-10.% and that
      of total essential oils was 2.0-3.3% of the dry werght of the cultured cells. The
      quantity, quality, and proportions of the volatile sesquiterpenoids of the cell
      culture were almost equal to those of intact (original) plants and
      redifferentiated plantlets. 

PMID- 24302204
TI  - Calcium-binding protein in sieve tube exudate.
AB  - A calcium-binding macromolecule, with an estimated molecular weight greater than
      100,000, was detected in phloem exudate from Cucurbita maxima and related
      species. The macromolecule was a component of sieve tube sap, rather than a
      contaminant leached from cell walls or cut parenchyma cells during exudate
      collection. The protein nature of this macromolecule was deduced from its size,
      lability, susceptibility to proteolytic digestion, and by the dependence of
      calcium-binding activity on thiol-protecting agents. This protein is distinct
      from the major proteins of exudate and does not appear to be related to
      calmodulin. 

PMID- 24302205
TI  - The effects of infection by Phytophthora infestans on the control of
      phenylpropanoid metabolism in wounded potato tissue.
AB  - During the first 24 h of in vitro incubation of excised potato tuber (Solanum
      tuberosum L.) discs, the appearance of phenylalanine ammonia-lyase (PAL; EC
      3.4.1.5) and the accumulation of chlorogenic acid are both stimulated by
      infection with Phytophthora infestans (Mont.) de Bary. Whereas in control tissue
      the level of PAL reached a stable plateau value after 40 h, in infected tissue it
      subsequently rose again, in one experiment, as the fungal mycelium developed. In
      the infected but not the control tissue, the level of chlorogenic acid
      subsequently fell to about to about 20% of its maximum after 50 h. The time
      courses of increases in cinnamic acid 4-hydroxylase (CA4H; EC 1.14.13.11; 0-60 h)
      and of caffeic acid acid o-methyltransferase (COMT; EC 2.1.1.42; 0-160 h) are not
      altered by fungal infection. If the discs are restored to the tuber environment
      immediately after excision, by placing them inside a "host tuber", the activity
      of PAL as well as those of CA4H and COMT remained at the constant low endogenous
      level for at least 60 h, irrespective of whether the discs had first been
      inoculated with P. infestans. The increase in PAL may not be an obligatory
      feature of the P. infestans/potato compatible interaction but dependent on an
      underlying wound response. The experiments provide further evidence that PAL is
      the rate limiting step of chlorogenic acid biosynthesis in potato tuber discs. 

PMID- 24302206
TI  - Lag-phase and rate of synthesis in light-mediated anthocyanin synthesis.
AB  - Mustard (Sinapis alba L.) seedlings were irradiated with continuous far-red light
      either with or without a pretreatment with 3 or 6 h of the same far-red light,
      separated by a 15 h dark period. The pretreatment increases the initial rate of
      anthocyanin accumulation - as caused by the 2nd light treatment - at least 6-fold
      but leads to an earlier cessation of anthocyanin accumulation. Moreover, the
      pretreatment seems to shorten the apparent lag-phase of anthocyanin accumulation
      considerably but it does not eliminate the lag. If the pretreatment with far-red
      light is terminated before the seedling reaches competence (with regard to
      phytochrome and anthocyanin synthesis) the pretreatment has no effect on the
      apparent lag-phase even though the future capacity of anthocyanin biogenesis is
      considerably stimulated by the pretreatment. The time course of induction of
      anthocyanin and that of phenylalanine ammonia-lyase (PAL) (Acton et al. 1980,
      Fig. 1) is in line with the concept that induction of PAL by light is a
      prerequisite for the onset of light-mediated anthocyanin synthesis. 

PMID- 24302207
TI  - Effect of the lithium chloride on the leaf movements of Cassia fasciculata.
AB  - LiCl inhibits the nyctinastic closure of folioles of excised leaves and enhances
      their opening, if there are 3 h before the light is switched off or on; the
      minimal concentration for significant effects on closure is 3.10(-4) M, and on
      opening 3.10(-3). The use of chlorides of other cations and other Li salts showed
      specificity of the lithium for the closure movement, the effect being reversed by
      KCl and NaCl. For the opening movement the Li effect is less specific. These
      results are compared to those obtained in other phenomena. 

PMID- 24302208
TI  - Isolation and biochemical characterization of grape malic enzyme.
AB  - Malic enzyme (ME=L-malate: NADP oxidoreductase; E.C. 1.1.1.40) was extracted by
      Triton X-100-induced resolubilization of enzyme proteins which denaturize
      spontaneously upon homogenization of grape berry material. The purification
      procedure included fractionating with (NH4)2SO4, preparative IEF, and Sephadex G
      100 chromatography. ME was identified by TLC of the radioactive product after
      supplementing the assay mixture with [(14)C]malate. Cofactor dependence, pH
      optimum and affinities for substrates and cosubstrates were determined. Enzymic
      pI was found to be 5.8, the Hill coefficients range from 1 to 3. In malate
      decarboxylating direction at pH 7.4, grape ME displayed positive cooperativity
      toward the substrate, the curve approaching normal Michaelis-Menten-kinetics at
      pH 7.0. Substituting Mn(2+) for Mg(2+) not only increased maximal turnover rates,
      but also enzymic affinity for malate. These features were considered indicative
      of the regulatory properties of the enzyme. Their relevance for grape malate
      metabolism and fruit ripening is discussed. 

PMID- 24302209
TI  - Quantitative ion localization within Suaeda maritima leaf mesophyll cells.
AB  - Grown under saline conditions, Suaeda maritima accumulates Na(+) and Cl(-) into
      its leaves, where individual mesophyll cells behave differently in their
      compartmentation of these ions. Measurements of ion concentrations within
      selected subcellular compartments show that freeze-substitution with dry
      sectioning is a valuable preparative technique for analytical electron microscopy
      of highly vacuolate plant material. Using this approach, absolute estimates were
      made of Na(+), K(+) and Cl(-) concentrations in the cytoplasm, cell walls,
      chloroplasts and vacuoles of leaf mesophyll cells. 

PMID- 24302210
TI  - Transport of assimilates in the developing caryopsis of rice (Oryza sativa L.) :
      Ultrastructure of the pericarp vascular bundle and its connections with the
      aleurone layer.
AB  - Assimilates entering the developing rice caryopsis traverse a short-distance
      pathway between the terminal sieve elements of the pericarp vascular bundle and
      the aleurone layer. The ultrastructure of this pathway has been studied. Sieve
      elements in the pericarp vascular bundle are smaller than their companion
      cells.The sieve elements show few connections with surrounding vascular
      parenchyma elements but are connected to companion cells by compound
      plasmodesmata. Companion cells, in turn, are connected to vascular parenchyma
      elements by numerous compound plasmodesmata present in wall thickenings.
      Assimilates leaving the sieve element - companion cell complex must laterally
      traverse cells of the pigment strand before they come into contact with the
      aleurone layer. The pigment strand cells have modified inner walls made up of a
      suberin-like material. This material may act as a permeability barrier isolating
      the apoplast from the symplast of the pigment strand. The walls of the pigment
      strand cells are traversed by numerous plasmodesmata. Water may be conducted to
      the endosperm through the isolated cell-wall system of the pigment strand while
      assimilates possibly move via plasmodesmata. High frequencies of plasmodesmata
      occur at the junction between the pigment strand and the nucellus and also
      between adjacent cells of the nucellus. By contrast, plasmodesmata are absent
      between the nucellus and the aleurone layer and also between the nucellus and the
      seed coat. A predominantly circumferential and symplastic transport pathway is
      likely between the pigment strand and nucellus. In view of the total absence of
      plasmodesmata between the nucellus and the aleurone layer assimilates entering
      the endosperm may have to cross the plasmalemma of the nucellus. It is possible
      that constraints to the flow of assimilates may occur in the short-distance
      pathway between the terminal sieve element - companion cell complexes and the
      endosperm, and this is discussed. 

PMID- 24302211
TI  - Synchronization and signal transmission in protoplasmic strands of Physarum :
      Effects of externally applied substances and mechanical influences.
AB  - The phenomenon of synchronization of contraction rhythms was investigated on
      isolated protoplasmic strands of Physarum polycephalum. The strands were mounted
      as (gymnastic) trapezes; the contraction activities of the arms were measured
      independently under isometric conditions; and the connecting middle part of the
      arms was treated in different ways to block the signal transmission between the
      arms. Experiments for testing the influence of different chemicals on signal
      transmission demonstrated that whenever a substance blocked signal transmission
      it also disturbed the normal oscillatory contraction activity of a single strand,
      the endoplasmic streaming, and the normal architecture of the strand. No
      substance inhibited the transmission of the synchronizing factor specifically. As
      a depolarizing medium, 70 mM KCl solution did not hinder phase synchronization.
      On the other hand, compression of the middle part with a glass needle immediately
      led to dissynchronization as soon as the endoplasmic flow could not pass the
      point of constriction. Gelation of the endoplasm by a vibrating glass needle
      placed at the surface of the middle part had the same effect. It is concluded
      that a bioelectric continuance of the plasmalemma is not sufficient for signal
      transmission. In contrast, an intact endoplasmic flow appears to be obligatory.
      According to the experimental data presented, an electrical coupling responsible
      for phase synchronization between the two arms seems to be unlikely. The unknown
      synchronizing factor is transported via endoplasmic flow, i.e., the endoplasmic
      stream seems to present the pacemaker of the oscillatory contraction activity. 

PMID- 24302212
TI  - Synchronization and signal transmission in protoplasmic strands of Physarum : The
      endoplasmic streaming as a pacemaker and the importance of phase deviations for
      the control of streaming reversal.
AB  - The importance of endoplasmic streaming in the synchronization of contraction
      activites in plasmodial strands of Physarum was investigated under experimental
      conditions allowing simultaneous observation of the endoplasmic flow in the
      middle part of a strand mounted as a trapeze and the measurement of isometric
      contraction activities of the arms of the trapeze, as well as of the activities
      of the strand portion connecting the arms. The correlation of longitudinal and
      radial contraction activities in different regions of a trapeze was examined.
      Whereas the arms and the middle part of a trapeze contract synchronously in a
      longitudinal direction (in-phase behaviour), an antiphase correlation appeared
      when comparing the longitudinal contraction activity of the arms and the radial
      activity of the middle part. This result is interpreted to mean that the middle
      part is able to perform isotonic contractions which induce radial dilatation of
      the strands. No clear-cut correlation between longitudinal and radial activities
      could be found when measuring simultaneously both activities in one and the same
      arm of a trapeze by combining tensiometry and cinematography. Protoplasmic
      shuttle streaming within a strand mounted as a trapeze is found to run regularly
      out of one arm through the middle part into the other arm, and vice versa. There
      is no correlation between the time points of streaming reversal and a certain
      stage of contraction cycles as presented by the contraction curves of the arms.
      However, there is a good correlation between the points of streaming reversal and
      the phase deviations of the longitudinal contraction activities of the arms. The
      importance of these phase deviations for the control of streaming reversal, i.e.,
      for the generation of hydrostatic pressure differences in a system working with
      phase synchrony, is discussed. The role of endoplasmic streaming as a pacemaker
      for synchronization phenomena of contraction activities is stressed. The
      possibility is discussed that shuttle streaming of endoplasm acts as a mechanical
      coupling within the regulation phenomena resulting in spatial monorhythmicity. 

PMID- 24302213
TI  - Graphene nanopores: electronic transport properties and design methodology.
AB  - Graphene nanopores (GNPs) hold great promise as building blocks for electronic
      circuitry and sensors for biological and chemical sensing applications. Methods
      to design graphene nanopores that achieve desirable conduction performance and
      sensing characteristics have not been previously described. Here we present a
      study of the quantum transport properties of GNPs created by drilling pores in
      armchair and zigzag graphene ribbons. For the first time, our study reveals that
      the quantum transmission spectra of GNPs are highly tunable and GNPs with
      specific transport properties can be produced by properly designing pore shapes.
      Our investigation shows that the biological sensing capabilities of GNPs are
      transmission spectrum dependent, can vary dramatically, and are critically
      dependent on pore geometry. Our study provides design guidelines for creating
      graphene nanopores with specific transport properties to meet the needs of
      diverse applications and for developing sensitive biological/chemical sensors
      with required performance characteristics. 

PMID- 24302216
TI  - Interventional cardiology: does an optimal antithrombotic regimen for PCI exist?

PMID- 24302217
TI  - Anticoagulation therapy: genotype-guided anticoagulation therapy-the jury is
      still out.

PMID- 24302220
TI  - Heart failure: addition of vasodilators to diuretic therapy does not improve
      outcome in acute heart failure.

PMID- 24302221
TI  - Valvular disease: mitral valve repair and replacement compared.

PMID- 24302222
TI  - Cardiac resuscitation: therapeutic hypothermia after out-of-hospital cardiac
      arrest.

PMID- 24302223
TI  - Acute coronary syndromes: medical adherence after discharge.

PMID- 24302224
TI  - Greenhouse-grown bitter melon: production and quality characteristics.
AB  - BACKGROUND: Bitter melon (Momordica charantia L.) is a medicinal fruit reported
      to have antidiabetic properties. To grow this tropical fruit year-round in
      temperate climates, greenhouse production is necessary, sometimes without insect
      pollinators. Suitable high-yielding varieties with good bioactivity need to be
      identified. This experiment evaluated the yield of six varieties of bitter melon
      under greenhouse conditions and their bioactivity in terms of total phenolic and
      saponin compounds and total antioxidant activity determined using four assays.
      RESULTS: The larger varieties (Big Top Medium, Hanuman, Jade and White) were more
      productive than the small varieties (Indra and Niddhi) in terms of total fruit
      weight and yield per flower pollinated. The bioactivity (total phenolic and
      saponin compounds and antioxidant activity) of the two small varieties and Big
      Top Medium was significantly higher than that of the other three large varieties.
      Two antioxidant assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing
      antioxidant power (FRAP), were shown to provide the strongest correlations with
      phenolic and saponin compounds of bitter melon. CONCLUSION: Preliminary research
      has identified Big Top Medium as the most suitable variety for greenhouse
      production. The rich source of phenolic and saponin compounds and their
      associated antioxidant activity highlight bitter melon as a valuable food.

PMID- 24302225
TI  - Experiences of hypoglycaemia unawareness amongst people with Type 1 diabetes: A
      qualitative investigation.
AB  - OBJECTIVES: To explore the experiences of people who have hypoglycaemia
      unawareness and its impact on their everyday lives. METHODS: In-depth interviews
      with 38 people with Type 1 diabetes who have hypoglycaemia unawareness. Data
      analysis used an inductive, thematic approach. RESULTS: Participants reported
      imposed and self-imposed changes to their lives following onset of hypoglycaemia
      unawareness including: leaving employment, curtailing pastimes and spending more
      time at home or being supervised by others. However, some reported getting on
      with life by downplaying the significance and impact of their condition, which
      could put their health and safety at risk. Many relied on frequent self
      monitoring of blood glucose and/or prompting from others to detect hypoglycaemia.
      Some expressed concerns about becoming a burden on family and/or responding in
      irrational and aggressive ways to others' suggestions to test for and treat
      hypoglycaemia. Participants reported responding best to composed and directive
      prompts from family. Health professionals mainly advised on clinical aspects, and
      did not enquire about the emotional and psychosocial impact of hypoglycaemia
      unawareness. DISCUSSION: Hypoglycaemia unawareness can have a profound impact on
      people's confidence, careers and personal relationships. Healthcare professionals
      should pay more attention during consultations to the emotional and social
      aspects of living with hypoglycaemia unawareness.

PMID- 24302227
TI  - Editorial.

PMID- 24302226
TI  - Steric vs. electronic effects in the Lactobacillus brevis ADH-catalyzed
      bioreduction of ketones.
AB  - Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly
      employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a
      chloromethyl as a small ketone substituent to the corresponding (R)-alcohols.
      Herein we have tested a series of 24 acetophenone derivatives differing in their
      size and electronic properties for their reduction employing LBADH. After
      plotting the relative activity against the measured substrate volumes we observed
      that apart from the substrate size other effects must be responsible for the
      activity obtained. Compared to acetophenone (100% relative activity), other small
      substrates such as propiophenone, alpha,alpha,alpha-trifluoroacetophenone, alpha
      hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than
      30%, while medium-sized ketones such as alpha-bromo-, alpha,alpha-dichloro-, and
      alpha,alpha-dibromoacetophenone presented relative activities between 70% and
      550%. Moreover, the comparison between the enzymatic activity and the obtained
      final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2
      propanol, denoted again deviations between them. These data supported that these
      hydrogen transfer (HT) transformations are mainly thermodynamically controlled.
      For instance, bulky alpha-halogenated derivatives could be quantitatively reduced
      by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic
      values. Finally, we found good correlations between the IR absorption band of the
      carbonyl groups and the degrees of conversion obtained in these HT processes,
      making this simple method a convenient tool to predict the success of these
      transformations. 

PMID- 24302228
TI  - A simple and efficient procedure for isolating plant chromatin which is suitable
      for studies of DNase I-sensitive domains and hypersensitive sites.
AB  - A simple and rapid procedure has been developed for the isolation of chromatin
      from plant leaves. The molecular weight of the DNA extracted from these chromatin
      preparations is comparable to that of DNA isolated by a conventional purification
      procedure (CTAB-CsCl-method). These results suggest that almost no degradation
      occurs during the isolation procedure. The effect of DNase I on three different
      groups of genes was studied; one of them, encoding the NADPH-protochlorophyllide
      oxidoreductase (PCR), represents a gene which is actively transcribed in
      etiolated leaf tissue. The other genes examined encode the hordein seed storage
      protein and 26S ribosomal RNA. The hordein genes are known to be inactive in
      leaves.The hordein and rDNA genes were found to be resistant to low levels of
      DNase I, while the gene for the PCR was highly sensitive to DNase I. During the
      course of digestion of the PCR gene, discrete cleavage products are generated.
      These indicate the presence of DNase I hypersensitive sites in the vicinity of
      the PCR gene in etiolated leaves. As a control 'naked' DNA has been digested with
      DNase I. No differences in sensitivity between the PCR gene and the hordein genes
      can be detected. 

PMID- 24302229
TI  - Synthesis of 5S rRNA and putative precursor tRNAs in nuclei isolated from wheat
      embryos.
AB  - Nuclei isolated from wheat embryos synthesize 4.5S precursor tRNAs and 5S rRNA in
      vitro. The precursor tRNAs can be processed to 4S tRNAs. Transcription of the
      tRNA and 5S rRNA genes is carried out by endogenous RNA polymerase III, and
      addition of exogenous wheat RNA polymerase III results in increased transcription
      on these genes. A number of experimental results suggest that proper initiation
      and accurate transcription of the tRNA and 5S rRNA genes occurs with isolated
      wheat nuclei. 

PMID- 24302230
TI  - The expression of chloroplast genes during cotton embryogenesis.
AB  - The expression of chloroplast genes during cotton embryogenesis was followed by
      measuring hybridization of cloned chloroplast genomic fragments to total RNA
      immobilzed on membrane filters. RNA was extracted from the cotyledons of cotton
      embryos at different stages of development ranging from very small embryos (5 mg)
      to the mature dry seed and from the cotyledons of seeds germinated for several
      days. The clones used in the hybridization reaction were those for 4 known
      chloroplast genes and one chloroplast sequence whose protein product is yet to be
      determined; all are from organisms other than cotton. The results of these dot
      blot hybridizations show that these genes are expressed as RNA constitutively
      during embryogenesis and that this expression increased between 5 and 20-fold
      (depending on the genomic sequence) during germination. In some cases it appears
      that these genes are expressed at a higher level in very young embryos than in
      more mature embryos. These results are surprising since cotton cotyledons are not
      exposed to light during embryogenesis and are not green at any embryonic
      stage.The extent of artifactual hybridization signals due to the presence of
      ctDNA in the RNA preparations was measured by treating the RNA on the filters
      with DNase I prior to hybridization with a labeled probe. To determine if the
      increased expression of these genes observed during germination is correlated
      with an increase in chloroplast genomes per cell, we followed the levels of ctDNA
      during embryogenesis and germination by hybridization of the clones to total DNA
      from different developmental stages. Although ctDNA per cell increases in the
      cotyledons during early germination in light or dark conditions, this increase is
      less than the increase observed in the mRNA levels, suggesting that the
      transcription rate increases or the mRNA degradation rate decreases for these
      genes during early germination. 

PMID- 24302231
TI  - Polymorphism and gene arrangement among plastomes of ten Epilobium species.
AB  - Plastid DNAs of ten different Epilobium species from four continents have been
      analysed using the restriction endonucleases BamHI, BglI, BglII, EcoRI, PstI,
      PvuII and SalI. With respect to the position of cleavage sites of those enzymes,
      each species has a specific plastome. Fragment patterns of different species from
      the same continent show a higher degree of similarity than those from different
      continents. Physical maps of the circular plastid DNA molecule have been
      constructed for each of the ten species by localising the cleavage sites of the
      enzymes BglI, PvuII and SalI. As in most other higher plants, the plastid DNA of
      Epilobium is segmentally organized into two inverted repeats separated by a large
      and a small single copy region. In heterologous hybridization experiments using
      radioactively labelled gene probes, the positions of structural genes coding for
      the rRNAs and for seven polypeptides have been determined. In contrast to its
      closest relative, Oenothera, the gene arrangement of Epilobium plastomes has the
      same order as in spinach. This indicates that changes in gene arrangement may be
      genus-specific and not the result of one or several events affecting all members
      of a plant family. 

PMID- 24302232
TI  - Relationship of viroids and certain other plant pathogenic nucleic acids to group
      I and II introns.
AB  - The nucleotide sequences of viroids contain features believed to be essential for
      the splicing of group I introns. Common sequence elements include a 16-nucleotide
      consensus sequence and three pairs of short sequences arranged in the same
      sequential order in both types of RNAs. The calculated probability of finding
      sequences resembling the 16-nucleotide consensus sequence in random nucleotide
      chains showed that at low fidelity (up to 5 mismatched nucleotides), the number
      of such sequences in viroids, plant viral satellite RNAs, plant viral RNAs and
      one plant viral DNA, group I introns and flanking exons does not significantly
      differ from the number expected at random. As the degree of fidelity is
      increased, the number in both introns and viroids, but not in exons or the other
      plant pathogens examined, greatly exceeds that expected in random chains. These
      findings suggest that viroids may have evolved from group I introns and/or that
      processing of viroid oligomers to monomers may have structural requirements
      similar to those of group I introns. The nucleotide sequences of viroids do not
      show close homology with two conserved regions of group II introns, the 14-base
      pair consensus region and the 5' terminal segment. However, close homology does
      exist between the conserved sequence of the 3' terminal segment of group II
      introns and viroids thus suggesting a possible evolutionary or functional
      relationship. 

PMID- 24302233
TI  - Divergence of chloroplast gene organization in three legumes: Pisum sativum,
      Vicia faba and Phaseolus vulgaris.
AB  - Isolated chloroplasts from Pisum sativum were found to contain at least 32 tRNA
      species. Hybridization of in vitro labeled, identified, chloroplast tRNAs to
      Pisum chloroplast DNA fragments revealed the locations of the tRNA genes on the
      circular chloroplast genome. Comparison of this gene map to the maps of Vicia
      faba and Phaseolus vulgaris showed that the chloroplast genomes of Pisum and
      Phaseolus are otherwise more closely related than either genome is to the
      chloroplast genome of Vicia. Furthermore, the results suggest how possible
      recombination events could be involved in the evolution of these three closely
      related, but divergent, chloroplast genomes. 

PMID- 24302234
TI  - Use of a sex attractant and an inhibitor for monitoring winter moth and bruce
      spanworm populations.
AB  - A single sex pherormone component was isolated from abdominal tip extracts of
      female Bruce spanworm.Operophtera bruceata (Hulst). This was identified as
      (Z,Z,Z)-1,3,6,9-nonadecatetraene by capillary gas chromatography (GC),
      electroantennography, and mass spectrometry. In addition, hexane extracts of
      female abdominal tips from Bruce spanworm and the winter moth.O. brumata L., were
      analyzed by GC coupled to an electroantennographic detector (GC-EAD). The
      extracts ofO. bruceata andO. brumata females elicited only a single response, at
      the same retention time, from antennae of their conspecific and reciprocal males.
      In field tests conducted in Saskatchewan, traps baited with the synthetic
      tetraene captured Bruce spanworm males. In tests carried out on Vancouver Island,
      British Columbia, where the two species coexist, both Bruce spanworm and winter
      moth males were captured. The attractancy of lures containing the synthetic
      pheromone alone and in combination with several structurally related analogs was
      field tested at both locations. One of these, an isomer of the natural pheromone,
      (E,Z,Z)-1,3,6,9-nonadecatetraene, inhibited the capture of Bruce spanworm males
      but had no effect upon the number of winter moth males which were taken. Thus,
      populations of these two very similar species can be distinguished by employing
      traps baited with pheromone +/- the inhibitor. Coneorifice Hara traps were found
      useful for field trapping males of both species. 

PMID- 24302235
TI  - Analysis of long-range reproductive behavior of maleDiabrotica virgifera
      virgifera leconte andD. Barberi Smith and Lawrence to stereoisomers of 8-methyl-2
      decyl propanoate under laboratory conditions.
AB  - Behavioral analysis of male attraction to stereoisomers of 8-methyl-2-decyl
      propanoate was conducted withDiabrotica virgifera virgifera andD. barberi using a
      flight tunnel.D. barberi males were attracted to the 2R,8R isomer only, and the
      response was inhibited by the addition of 2S,8R.D. v. virgifera males were also
      attracted to the 2R,8R isomer and were neither attracted nor inhibited by any of
      the other isomers. Males attracted to the lures displayed a series of behaviors
      characterized by a slow hovering flight upwind towards the odor source. While
      significant numbers of males of both species landed on the pheromone lure, none
      attempted copulation, indicating that other cues are necessary to induce this
      behavior. 

PMID- 24302236
TI  - Effects of monoterpene odors on food selection by red deer calves (Cervus
      elaphus).
AB  - The response of red deer calves (Cervus elaphus) to the odors of Sitka spruce
      (Picea sitchensis) and lodgepole pine (Pinus conforta) needles and five
      monoterpene constituents of their essential oils was measured by simple two
      choice feeding trials. All odors were significantly rejected (P < 0.05) except
      Sitka spruce and lodgepole pine by females and Sitka spruce and alpha-terpineol
      by males. Females had a stronger dislike of all odors except lodgepole pine than
      males. Rejection of monoterpene odors weakened slightly with time. A strong
      logarithmic relationship between the strength of the rejection response and vapor
      pressure of the compounds tested suggested that the odors were rejected on the
      basis of concentration rather than quality. 

PMID- 24302237
TI  - Identification of unique pheromone components for soybean looper mothPseudoplusia
      includens.
AB  - Analysis of sex pheromone glands from individual female soybean looper moths
      showed that in addition to the previously identified main component (Z)-7
      dodecenyl acetate, the compounds dodecyl acetate, 11-dodecenyl acetate, (Z)-7
      dodecenyl propionate, and (Z)-7-dodecenyl butanoate were also produced. Two of
      the components, 12?OAc and 11-12?OAc, were not detected in a single analysis of
      female effluvium. Flight-tunnel tests showed that the five-component and three
      component blends were equal to each other and to a female extract (> 80% source
      contacts) and that the mixtures were superior toZ7-12?OAc alone. Field tests
      indicated that the five-component blend was significantly more attractive thanZ7
      12?OAc alone at a dosage of 1 mg, but that the blend was only slightly better at
      3 mg. 

PMID- 24302238
TI  - Isolation and structure determination of new nematicidal triglyceride
      fromArgemone mexicana.
AB  - The petroleum ether extract ofArgemone mexicana seeds was found to possess
      nematicidal activity against the plant parasitic nematodeMeloidogyne incognita.
      The active nematicidal compound has been isolated from the crude extract by
      column Chromatographic techniques and purified by TLC. Chemical structure has
      been determined by chemical and spectro-scopic methods to be that of a
      triglyceride, sn-glycerol-1-eicosa-9, 12-dien-oate-2-palmitoleate-3-linoleate. 

PMID- 24302239
TI  - Sex pheromone components of three species ofSemiothisa (Geometridae), (Z,Z,Z)
      3,6,9-heptadecatriene and two monoepoxydiene analogs.
AB  - Adult males ofSemiothisa signaria dispuncta (Walker) were attracted to field
      traps baited with (Z,Z,Z)-3,6,9-octadecatriene and (Z,Z)-6,9-cis-3,4-epoxy
      octadecadiene. However, analyses of sex pheromone gland extracts of females of
      this species by GC-MS and by GC in combination with an electroantennograph
      detector (GC-EAD) showed the pheromone to be comprised of a mixture of the next
      lower homologs: (Z,Z,Z)-3,6,9-heptadecatriene and (Z,Z)-6,9-cis-3,4-epoxy
      heptadecadiene. Blends of these two C17 compounds were subsequently found to be
      more attractive to males in the field than the corresponding C18 mixtures. Sex
      pheromones of two otherSemiothisa species were also found to contain C17
      components. (Z,Z,Z)-3,6,9-Heptadecatriene, detected by GC-EAD analysis of a
      female abdominal tip extract ofS. bicolorata (Fabricius), attracted conspecific
      males, and this attraction was significantly reduced by additions of (Z,Z)-6,9
      cis-3,4-epoxyheptadecadiene, the major pheromone component ofS. signaria
      dispuncta, to the lure. (Z,Z)-3,9-cis-6,7-Epoxy-heptadecadiene was detected by GC
      EAD analysis as the primary male antennal stimulatory component present in
      abdominal tip extracts ofS. ulsterata (Pearsall), and males of this species were
      attracted to traps baited with this epoxide. Each of these three C17 compounds
      constitute previously unknown lepidopteran sex pheromone components. Blends of
      (Z,Z, Z)-3,6,9-heptadecatriene and (Z,Z)-3,9-cis-6,7-epoxyheptadecadiene
      attracted males of a fourth species,S. delectata Hulst, but no females of this
      species were obtained to permit analysis of its sex pheromone. The occurrence of
      (Z,Z,Z)-3,6,9-heptadecatriene inS. neptaria (Guenee) females was indicated by GC
      MS analysis of an abdominal tip extract; however, no males were attracted to any
      of the fielded mixtures containing this hydrocarbon. 

PMID- 24302240
TI  - Pheromonal basis for aggregation behavior of parasitoids of the gypsy
      moth:Brachymeria intermedia (Nees) andBrachymeria lasus (Walker) (Hymenoptera:
      Chalcididae).
AB  - The parasitoidsB. intermedia andB. lasus aggregate at sites previously
      frequented. Extracts from filter paper conditioned by aggregated parasitoids were
      chromatographed (adsorption column and gas-liquid chromatography) and bioassayed.
      An active component that elicited aggregation response forB. intermedia was
      isolated and identified as 3-hexanone. This molecule was found in trace
      quantities (5-10 ng/female or male) on filter paper conditioned by either male,
      female or a combination of the sexes. 

PMID- 24302241
TI  - Field response and gas-liquid chromatograph separation of optically active
      synthetic and natural pheromones in two sympatric diprionid sawflies,Neodiprion
      nanulus nanulus andNeodiprion sertifer (Hymenoptera: Diprionidae).
AB  - The male red pine sawflyNeodiprion nanulus nanulus Schedl responds mainly to the
      (2S,3S,7S)-3,7-dimethylpentadecan-2-yl acetate (2S,3S,7S-A) in the field. No
      other isomer is as effective by itself or syner-gizes 2S,3S, 7S-A in this
      species. ForNeodiprion sertifer (Geoffroy), however, we confirmed our earlier
      report that males responded significantly to a 5?0.003 mixture of 2S,3S,7S-A and
      either 2S,3R,7R-A or 2S,3R,7R/S-A. The 2S,3S,7S-A isomer was separated from
      2S,3R,7R-A by capillary gas-liquid chromatographic (GLC) analysis using Carbowax
      20 M and DB-5 columns. The latter column also separated 2S,3S,7S-A from 2S,3R,7S
      A. Only 2S,3S,7S-A was found in the natural pheromones ofN. n. nanulus andN.
      sertifer by GLC analysis. 

PMID- 24302242
TI  - Efficacy of pine oil as repellent to wildlife.
AB  - Pine oil, a by-product of the pulp industry, is a feeding repellent to snowshoe
      hares and voles. In pen trials with snowshoe hares and field trials with voles,
      when given a choice between food in a pine oil-treated bowl and a control bowl,
      the animals fed preferentially from the control bowl. When the hares were
      presented with food only in a pine oil-treated bowl, two hares showed a reduced
      rate of food consumption and one hare did not feed at all. Pine oil contains
      monoterpenes which may inhibit microbial symbionts in the digestive tracts of
      hares and voles. The repellent action of pine oil is likely based on this
      interference of digestive processes, and it is of adaptive advantage for cecal
      digestors to avoid it. Pine oil has potential as a commercial repellent for
      snowshoe hares and voles. 

PMID- 24302243
TI  - Chemical basis for asymmetric mating isolation between strains of screwworm
      fly,Cochliomyia hominivorax.
AB  - Laboratory mating tests and bioassays for a contact, mating-stimulant pheromone
      were conducted within and between two strains of the screwworm fly,Cochliomyia
      hominivorax. No strain or sex difference in pheromone activity occurred at
      emergence. However, the pheromone activity of females increased with age in one
      strain but declined in the other. Activity also declined in males of both strains
      but more steeply than in the females. Thus, sexual dimorphism in pheromone
      activity developed with age in both strains but to differing degrees. The decline
      in female pheromone activity was partly compensated for within that strain by a
      higher male responsiveness to pheromone. Female pheromone activity and mating
      success were positively correlated. Virgin females and those inseminated 24-48 hr
      previously were equally stimulatory. It appears that the strain differences arose
      from selection for reduced pheromone activity during laboratory colonization. 

PMID- 24302244
TI  - Repeatability of pheromone emissions from individual female ermine
      mothsYponomeuta padellus andYponomeuta rorellus.
AB  - The repeatability of the composition of pheromone emitted by individual female
      moths (Yponomeuta) was determined by gas Chromatographic analysis. An improved
      technique for repeated collections of airborne volatiles from the same moth was
      developed. The procedure did not harm the females and allowed precise
      quantification of 0.05 ng of pheromone components in 30-min collections.
      Individual females ofY. padellus (N=10) andY. rorellus (N=5) were sampled six and
      eight days after emergence.Y. padellus released, on average, 4.8 ng/30 min of
      tetradecyl acetate, (E)-11-tetradecenyl acetate, (Z)-11-tetradecenyl acetate,
      hexadecyl acetate, (Z)-9-hexadecenyl acetate, and (Z)-11-hexadecenyl acetate in
      the average ratio 445?38?100?494?35?421. The amount of (E)-11-tetradecenyl
      acetate relative to (Z)-11-tetradecenyl acetate was less variable [coefficient of
      variation (CV)=15%] than the relative amounts of the other components (CV=46
      61%). The repeatability of the relative amounts of compounds released by
      individual females was high for all components (r=0.82-0.90). The average
      emission of tetradecyl acetate, tetradecanol, hexadecyl acetate, and hexadecanol
      byY. rorellus was 8.3 ng/30 min (ratio 100?8?10?2). The repeatability was low for
      tetradecanol (r=0.51) but higher for hexadecyl acetate (r=0.87) and hexadecanol
      (r=0.89). The low interindividual variance for the (E)-11-/(Z)-11-tetradecenyl
      acetate ratio inY. padellus might be due to its importance for reproductive
      isolation, i.e., it is under strong selection pressure. 

PMID- 24302245
TI  - Comparison of electroantennograms from female and male cabbage looper moths
      (Trichoplusia ni) of different ages and for various pheromone concentrations.
AB  - The electroantennogram (EAG) responses of both male and femaleTrichoplusia ni to
      two components of the female-released sex pheromone were determined over a range
      of concentrations of chemical and age of insect. The EAG was at a peak at a dose
      of 100 MUg for both dodecyl acetate and (Z)-7-dodecenyl acetate (Z7-12?OAc) for
      both sexes. The EAG responses varied with age of the insect. Responsiveness to
      both components was at a maximum at three days postemergence for males followed
      by a fairly rapid senescence, and for females it peaked at three days followed by
      a rapid senescence forZ7-12?OAc but not for dodcecyl acetate. 

PMID- 24302246
TI  - Monoterpene metabolism in female mountain pine beetles,Dendroctonus ponderosae
      Hopkins, attacking ponderosa pine.
AB  - Abdominal volatiles of female mountain pine beetles,Dendroctonus ponderosae
      Hopkins, fed in ponderosa pine,Pinus ponderosa Dougl. ex Laws, and in lodgepole
      pine,P. contorta var.latifolia Engelmann, were analyzed by gas chromatography and
      coupled gas chromatography-mass spectrometry and were found to comprise host
      oleoresin components and beetle-produced alliylic alcohols, aldehydes, and
      ketones derived from host monoterpenes. Neitherexo- andendo-brevicomin nor
      frontalin were detected. Three metabolic pathways are proposed to account for the
      distribution of beetle-produced monoterpene alcohols. The first pathway involves
      hydroxylation of monoterpene substrates on allylic methyl groups which areE to a
      methylene or vinyl group. This oxidation pathway is indiscriminate with respect
      to substrate and probably functions to detoxify monoterpenes. A second pathway,
      which hydroxylates theendo-cyclic methyleneE to a vinyl methyl group of bicyclic
      monoterpenes to give almost exclusively thetrans alcohol, is hypothesized to be
      involved in pheromone production. A third detoxification pathway involves anti
      Markovnikov addition of water to theexo-cyclic double bond of beta-phellandrene
      to give predominantlytrans-2-p-menthen-7-ol. 

PMID- 24302247
TI  - Solution volume and seed number: Often overlooked factors in allelopathic
      bioassays.
AB  - Cucumber seeds were germinated under various combinations of solution volume and
      seed number with a range of ferulic acid concentrations. At each concentration,
      radicle growth decreased as the relative amount of ferulic acid available per
      seed increased from chi (25 seeds/5 ml) to 5chi (5 seeds/5 ml) to 19chi (25
      seeds/95 ml). With 2.0 mM ferulic acid in buffered solution, radicle lengths
      after 48 hr ranged from 71 to 47% of control. The amount of ferulic acid
      remaining in 2.0 mM solution after 48 hr was directly proportional to the amount
      initially available per seed, and ranged from 9 to 91%. Solution volume and seed
      number also significantly affected inhibition by vanillic acid, caffeic acid, and
      juglone. With 0.1 mM juglone, radicle lengths after 48 hr were 88% of control
      with 25 seeds/5 ml, 68% with 5 seeds/5 ml, and 56% with 25 seeds/90 ml. The data
      demonstrated that lower phytotoxin concentrations can produce equivalent or
      greater inhibitory effects than higher concentrations when the amount available
      per seed for uptake is greater. Equivalent inhibition of radicle growth was
      observed with 1.0 mM (5 seeds/5 ml) and 2.0 mM (25 seeds/5 ml) ferulic acid.
      Available literature on herbicides indicates that similar effects occur in
      greenhouse and field studies. 

PMID- 24302248
TI  - Orientation behavior and effect of experience and laboratory rearing on responses
      ofCotesia melanoscela (Ratzeburg) (Hymenoptera: Braconidae) to gypsy moth silk
      kairomone.
AB  - Cotesia melanoscela responds the same way to the silk of its host, gypsy moth
      larvae,Lymantria dispar L., whether or not it has previously been exposed to
      hosts. Parasites maintained in the laboratory for six or 25 generations also
      responded similarly, suggesting that orientation behavior is not modified by
      laboratory rearing. Details of silk-related orientation behavior were analyzed by
      tracing paths of female parasites when on or off silk-covered substrates. Females
      made 31  degrees  average turns every 0.5 cm whether or not they were examining
      silk. They tended to turn back onto a silked area when encountering a border, and
      their speed of movement when not examining silk was about three times higher than
      when examining silk. 

PMID- 24302249
TI  - Attraction to pheromone sources of different quantity, quality, and spacing:
      Density-regulation mechanisms in bark beetleIps typographus.
AB  - The density of bark-beetle colonization of a tree could be regulated by a
      quantitative effect of the pheromone signal from beetles in the tree (cessation
      of release of attractive pheromone) or by a qualitative effect (production of
      pheromone components inhibiting attraction). The quantitative hypothesis was
      tested onIps typographus by varying the release rate of the two known attractive
      compounds, 2-methyl-3-buten-2-ol (MB) and (4S)-cis-verbenol (cV). The highest
      number of beetles were captured at traps with the highest release rates. The
      catch was nearly proportional to the release of MB and cV at a distance between
      traps of 12 m or more. At 6-, 3-, and 1.5-m distances between traps deployed in a
      triangular arrangement there was still a good discrimination between release
      rates, but relatively more beetles, especially males, were caught on the blank.
      The lower release rates caught an equal sex ratio while the highest release rate
      caught only about 30% males. The qualitative hypothesis was tested by releasing
      the suspected inhibitors ipsdienol (Id) and ipsenol (Ie), from traps in the same
      amounts as cV. Only small effects were noted forI. typographus. However, the
      competitorI. duplicatus was attracted to Id and inhibited by Ie, while the
      predatorThanasimus formicarius was attracted to both compounds. On the other
      hand, when the ratio of Id or Ie to cV was 10?1 or 0.1?1 rather than 1?1, they
      affected the numbers ofI. typographus attracted. A small amount of Id combined
      with the attractants increased trap catch, while large amounts of Id or Ie
      decreased attraction, especially when combined. Attack density regulation is
      modeled as an effect of both quantitative and qualitative mechanisms acting in
      sequence. 

PMID- 24302250
TI  - Influence of pheromone chirality on response byOryzaephilus surinamensis
      andOryzaephilus mercator (Coleoptera: Cucujidae).
AB  - The response of the sawtoothed grain beetle,Oryzaephilus surinamensis (L.), and
      the merchant grain beetle,O. mercator (Fauvel), to synthetic racemic and chiral
      macrolide aggregation pheromones was assessed in pitfall olfactometers.O.mercator
      utilizes theR enantiomers of (Z)-3-dodecen-11-olide and (Z,Z)-3,6-dodecadien-11
      olide.O. surinamensis utilizes theR enantiomers of (Z,Z)-3,6-dodecadien-11-olide
      and the Synergist (Z,Z)-5,8-tetradecadien-13-olide in combination with achiral
      (Z,Z)-3,6-dodecadienolide. For both species, the racemates of the respective
      chiral pheromones were effective attractants. The respectiveS enantiomers were
      inactive for both species and had no effect on the biological activity of the
      active antipodes. No diel periodicity in responsiveness to pheromones was
      detected inOryzaephilus spp. reared either on a 12?12 light-dark photoperiod or
      in darkness. Nonpheromone macrolides, naturally released in trace amounts
      byOryzaephilus spp., did not affect the aggregation response of either species to
      its pheromones when these additional macrolides were combined with the pheromone
      mixtures. 

PMID- 24302251
TI  - Chirality of macrolide pheromones of grain beetles in the
      generaOryzaephilusandCryptolestes and its implications for species specificity.
AB  - The chiralities of macrolide lactone aggregation pheromones of five species of
      economically important grain beetles have been determined by capillary gas
      chromatographic separation of the diastereomeric (S)-O-acetyllactate derivatives
      of the hydroxy methyl esters derived from boron trifluoride-catalyzed cleavage of
      the macrolides in methanol. Chirally pure (Z)-3-dodecen-11-olide (I) is produced
      in theS configuration byCryptolestes ferrugineus (Stephens) and in theR
      configuration byOryzaephilus mercator (Fauvel). (Z,Z)-3,6-Dodecadien-11-olide
      (II) is produced in theR configuration by bothO. mercator andO. surinamensis
      (L.). (Z,Z)-5,8-Tetradecadien-13-olide (IV) is produced in theR configuration
      byO. surinamensis and as a 85?15 mixture ofR andS isomers byC. turcicus. (Z)-5
      Tetradecen-13-olide (V) is produced in the S configuration byC. pusillus
      (Schonherr) and as a 33?67 mixture of theR andS isomers byC. turcicus
      (Grouvelle). The results indicate that in these cucujids, species specificity in
      pheromone response is maintained at least in part by pheromone chirality. 

PMID- 24302252
TI  - Methylbutynol effectively replaces methylbutenol, a pheromone component ofIps
      typographus (L.) (Coleoptera: Scolytidae).
AB  - In field experiments in Sweden, the constituent 2-methyl-3-buten-2-ol of the
      aggregation pheromone of the spruce bark bettleIps typographus (L.) was
      effectively replaced by 2-methyl-3-butyn-2-ol. 

PMID- 24302253
TI  - Validation of the Perceived Stress Scale in a community sample of older adults.
AB  - BACKGROUND: Three versions of Perceived Stress Scale (PSS-14, PSS-10, and PSS-4)
      are among the most widely used measures of stress. The aim of the current study
      was to validate this instrument in a sample of nondemented older adults to
      facilitate studies of the impact of stress on health. METHODS: Seven hundred
      sixty-eight nondemented adults over the age of 70 years completed the PSS-14
      questionnaire and other neuropsychological tests. Exploratory factor analysis was
      used to determine the underlying factor structure of all PSS versions, and
      confirmatory factor analysis was used to test the construct validity of factors.
      The internal consistency reliability of the scales was assessed using Cronbach's
      alpha, and concurrent validity was evaluated by examining PSS relation with age,
      gender, depression, anxiety, and Positive Affect and Negative Affect Schedule.
      RESULTS: A two-factor model was the optimal fit for the 14-item and 10-item
      versions of PSS. For PSS-14, all items' loadings exceeded 0.4 for one of the two
      factors except item 12. Therefore, we studied a 13-item version of PSS and 10
      item and 4-item subsets representing PSS-10 and PSS-4. Internal consistency
      coefficients were satisfactory for the full scale of PSS-13 and PSS-10 but not
      for PSS-4. Women reported higher levels of stress than men. Higher levels of
      total PSS scores showed association with higher levels of depression, anxiety,
      and negative affect, and lower level of positive affect. CONCLUSIONS: The 13-item
      and 10-item versions of PSS may be used to understand the experience of stress
      among older adults.

PMID- 24302254
TI  - The N-terminal membrane-spanning domain of the Escherichia coli DNA translocase
      FtsK hexamerizes at midcell.
AB  - Bacterial FtsK plays a key role in coordinating cell division with the late
      stages of chromosome segregation. The N-terminal membrane-spanning domain of FtsK
      is required for cell division, whereas the C-terminal domain is a fast double
      stranded DNA (dsDNA) translocase that brings the replication termination region
      of the chromosome to midcell, where it facilitates chromosome unlinking by
      activating XerCD-dif site-specific recombination. Therefore, FtsK coordinates the
      late stages of chromosome segregation with cell division. Although the
      translocase is known to act as a hexamer on DNA, it is unknown when and how
      hexamers form, as is the number of FtsK molecules in the cell and within the
      divisome. Using single-molecule live-cell imaging, we show that newborn
      Escherichia coli cells growing in minimal medium contain ~40 membrane-bound FtsK
      molecules that are largely monomeric; the numbers increase proportionately with
      cell growth. After recruitment to the midcell, FtsK is present only as hexamers.
      Hexamers are observed in all cells and form before any visible sign of cell
      constriction. An average of 7 FtsK hexamers per cell are present at midcell, with
      the N-terminal domain being able to hexamerize independently of the translocase.
      Detergent-solubilized and purified FtsK N-terminal domains readily form hexamers,
      as determined by in vitro biochemistry, thereby supporting the in vivo data. The
      hexameric state of the FtsK N-terminal domain at the division site may facilitate
      assembly of a functional C-terminal DNA translocase on chromosomal DNA.
      IMPORTANCE: In the rod-shaped bacterium Escherichia coli, more than a dozen
      proteins act at the cell center to mediate cell division, which initiates while
      chromosome replication and segregation are under way. The protein FtsK
      coordinates cell division with the late stages of chromosome segregation. The N
      terminal part of FtsK is membrane embedded and acts in division, while the C
      terminal part forms a hexameric ring on chromosomal DNA, which the DNA can
      translocate rapidly to finalize chromosome segregation. Using quantitative live
      cell imaging, which measures the position and number of FtsK molecules, we show
      that in all cells, FtsK hexamers form only at the cell center at the initiation
      of cell division. Furthermore, the FtsK N-terminal portion forms hexamers
      independently of the C-terminal translocase.

PMID- 24302255
TI  - Both terminal oxidases contribute to fitness and virulence during organ-specific
      Staphylococcus aureus colonization.
AB  - In their recent article, Hammer et al. (N. D. Hammer, M. L. Reniere, J. E.
      Cassat, Y. Zhang, A. O. Hirsch, M. Indriati Hood, and E. P. Skaar, mBio 4:e00241
      13, 2013) described the dual functions of the two terminal oxidases encoded by
      cydBA and qoxABCD in Staphylococcus aureus. The aerobic growth of cydB or qoxB
      single mutant bacteria was barely affected. However, a cydB qoxB double mutant
      was completely unable to respire and exhibited the small-colony variant phenotype
      that is typical of menaquinone and heme biosynthesis mutants. The authors found
      that the two terminal oxidases play a role in pathogenesis. In a systemic mouse
      infection model, it turned out that in the cydB mutant the bacterial burden was
      significantly decreased in the heart, kidneys, and liver, while in the qoxB
      mutant it was decreased only in the liver. These results illustrate that both
      terminal oxidases contribute to fitness and virulence, representing promising
      candidates for the development of antimicrobials.

PMID- 24302256
TI  - Luminescent alkynyl-gold(I) coumarin derivatives and their biological activity.
AB  - The synthesis and characterization of three propynyloxycoumarins are reported in
      this work together with the formation of three different series of gold(i)
      organometallic complexes. Neutral complexes are constituted by water soluble
      phosphines (PTA and DAPTA) which confer water solubility to them. The X-ray
      crystal structure of 7-(prop-2-in-1-yloxy)-1-benzopyran-2-one and its
      corresponding dialkynyl complex is also shown and the formation of rectangular
      dimers for the gold derivative in the solid state can be observed. A detailed
      analysis of the absorption and emission spectra of both ligands and complexes
      allows us to attribute the luminescent behaviour to the coumarin organic ligand.
      Moreover, the presence of the gold(i) metal atom seems to be responsible for an
      increase of coumarin phosphorescence emission. The biological activity of the
      complexes showed that the anionic complexes triggered strong cytotoxic effects in
      two different cell lines whereas the neutral gold alkynyl complexes led to lower
      effects against tumor cell growth. Thioredoxin reductase (TrxR) inhibition was
      very strong in the case of the neutral complexes (IC50 values below 0.1 MUM) but
      moderate for the anionic complexes (IC50 values above 0.8 MUM). 

PMID- 24302258
TI  - The next great change.

PMID- 24302257
TI  - Re: Elliott CS, Comiter CV. The effect of angiotensin inhibition on urinary
      incontinence: data from the National Health and Nutrition Examination Survey
      (2001-2008). Neurourol Urodyn 2014; 33:1178-81.

PMID- 24302259
TI  - Death anxiety: A hidden factor in countertransference hate.
AB  - We suggest that when diffucult patients attack our grandiosity and sense of self,
      we are vulnerable to countertransference anxieties similar, if not identical, to
      the kind existentialists refer to as "ontological". The latter refers
      specifically to a threat to our psychological equilibrium and is meant to
      describe the utter ambivalence we associate with death anxiety. In this paper, we
      are proposing the presence, in certain therapeutic situations, of just such
      counter-transference reactions to so-called "aversive" patients. We believe that
      terms like "aversive", "obnoxious", or "impossible" are professional euphemisms
      used to mask the degree of anxiety we often feel, and that there is a collusion
      present both within and without our profession, especially in psychotherapeutic
      and psychoanalytic centers, which keeps us from exploring death-related issues
      within ourselves as well as in our patients. 

PMID- 24302260
TI  - Religion and health: A theological reflection.
AB  - Are healthy people necessarily religious? Are religious people necessarily
      healthy? Does holism imply that holiness equals health? This paper presents a
      model for a multidimensional understanding of human progress that does not lose
      sight of the fundamental unity of personhood. 

PMID- 24302261
TI  - AIDS and ARC: Pastoral issues in the hospital setting.
AB  - Eight areas of fear for persons with Acquired Immune Deficiency Syndrome and its
      related conditions are explored: change and stress, uncertainty and the unknown,
      waiting, the fear of symptoms, fear of contagion, abandonment, dependency and
      spiritual distress. Some particular issues of sub-populations with HIV infection
      are detailed. Suggestions for helpful pastoral responses to the common concerns
      and anxieties of patients and their loved ones are offered. 

PMID- 24302262
TI  - Suffering and damage in Catholic sexuality.
AB  - This article suggests there may be a probable correlation between Catholic sexual
      orthodoxy and pathology in various Catholic cultures of the United States. There
      exists no empirically valid documentation suggesting the need for scientific
      research.In a series of private interviews conducted anonymously with religious
      and clinical professionals and a limited sample of lay opinion, there was near
      unanimous support for the idea of research linking sexual orthodoxy and pathology
      in the Catholic tradition, since the majority interviewed believe it is an
      undocumented fact based on clinical-pastoral observation and human experience. 

PMID- 24302263
TI  - "Heroic struggle": A medieval and modern dilemma.
AB  - In the medieval tale ofSir Gawain and The Green Knight there is a portrait of an
      archetypal hero who succumbs to the pressures of living up to his reputation by
      resorting to behavior which compromises the code of ethics of knighthood. The
      lives of contemporary men and women are much more complex by comparison, though
      not always quite so dramatic. The pressures we face on a daily basis are
      cumulatively greater. Choices we make may be determined by our need to filter the
      realities of our world through a "characterological lie" which we have fashioned
      in ourselves as a way of protecting a vulnerable psyche from the truths of
      existence. Events in this fourteenth-century narrative are reexamined in the
      light of Dr. Ernest Becker'sThe Denial of Death, which strongly implicates the
      confrontation between the individual and the environment. 

PMID- 24302264
TI  - Defining suicide: Importance and implications for Judaism.
AB  - One of the more problematic situations in the Jewish tradition is seeing to the
      psychological needs of the family of a suicide. This is due to the legal
      statements found within the tradition, placing some restrictions on the funeral
      rite. As a result of this, the criteria for the suicide are to be well examined
      and understood to ensure proper pastoral care. 

PMID- 24302265
TI  - Grief and attachment.
AB  - Loss and grief are universal phenomena with serious potential psychological and
      physical consequences. Loss results in various reactions that have been
      identified in a variety of ways. Attachment theory provides a conceptual scheme
      to understand these processes and consequences. Clergy are in a strategic
      position to respond to loss, and attachment theory helps inform pastoral
      intervention. Several program and research issues are posed that emerge from the
      author's clinical experience. 

PMID- 24302266
TI  - 25th anniversary article: what can be done with the Langmuir-Blodgett method?
      Recent developments and its critical role in materials science.
AB  - The Langmuir-Blodgett (LB) technique is known as an elegant method for
      fabrication of well-defined layered structures with molecular level precision.
      Since its discovery the LB method has made an indispensable contribution to
      surface science, physical chemistry, materials chemistry and nanotechnology.
      However, recent trends in research might suggest the decline of the LB method as
      alternate methods for film fabrication such as layer-by-layer (LbL) assembly have
      emerged. Is LB film technology obsolete? This review is presented in order to
      challenge this preposterous question. In this review, we summarize recent
      research on LB and related methods including (i) advanced design for LB films,
      (ii) LB film as a medium for supramolecular chemistry, (iii) LB technique for
      nanofabrication and (iv) LB involving advanced nanomaterials. Finally, a
      comparison between LB and LbL techniques is made. The latter reveals the crucial
      role played by LB techniques in basic surface science, current advanced material
      sciences and nanotechnologies. 

PMID- 24302267
TI  - Erratum to: Mesenchymal Stem Cells as Cellular Immunotherapeutics in Allogeneic
      Hematopoietic Stem Cell Transplantation.

PMID- 24302268
TI  - Air pollution and traffic noise: do they cause atherosclerosis?

PMID- 24302269
TI  - Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48.
AB  - AIMS: The complex relationship between left atrial (LA) structure and function,
      electrical burden of atrial fibrillation (AF) and stroke risk is not well
      understood. We aimed to describe LA structure and function in AF. METHODS AND
      RESULTS: Left atrial structure and function was assessed in 971 subjects enrolled
      in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size,
      emptying fraction (LAEF), and contractile function were compared across AF types
      (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke
      risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF,
      with an inverse relationship between LA size and LAEF (R = -0.57, P < 0.001).
      With an increasing electrical burden of AF and higher CHADS2 scores, LA size
      increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF
      despite normal LA size, and LA contractile dysfunction was present even among the
      subset of AF subjects in sinus rhythm at the time of echocardiography.
      CONCLUSIONS: In a contemporary AF population, LA structure and function were
      increasingly abnormal with a greater electrical burden of AF and higher stroke
      risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite
      normal LA size and sinus rhythm, suggesting that the assessment of LA function
      may add important incremental information in the evaluation of AF patients.
      CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; ID = NCT00781391.

PMID- 24302271
TI  - Possible joint pathways of early pre-eclampsia and congenital heart defects via
      angiogenic imbalance and potential evidence for cardio-placental syndrome.

PMID- 24302270
TI  - Treating hypertension in the very elderly-benefits, risks, and future directions,
      a focus on the hypertension in the very elderly trial.
AB  - Although the number of individuals reaching 80 who are considered to be healthy
      is increasing, the very elderly are likely to have long-term conditions, to
      report symptoms and/or be taking at least one regular medication. The impact of
      antihypertensive treatment has to be taken into account in this context. The
      treatment regimen in Hypertension in the Very Elderly Trial with a goal blood
      pressure of <150/80 mmHg has been shown to provide benefits in terms of a
      reduction in risk of total mortality, stroke, and cardiovascular events with
      potential benefits and no evidence of increased risk for fracture, dementia,
      depression, and quality-of-life outcomes. Questions remain as to the level of
      benefit that would be accrued in the frailer elderly and those at extreme age,
      for example, over 90.

PMID- 24302272
TI  - Short-term effects of air pollution on out-of-hospital cardiac arrest in
      Stockholm.
AB  - BACKGROUND: Although ozone (O3) and other pollutants have been associated with
      cardiovascular morbidity and mortality, the effects of O3 on out-of-hospital
      cardiac arrest (OHCA) have rarely been addressed and existing studies have
      presented inconsistent findings. The objective of this study was to determine the
      effects of short-term exposure to air pollution including O3 on the occurrence of
      OHCA, and assess effect modification by season, age, and gender. METHODS AND
      RESULTS: A total of 5973 Emergency Medical Service-assessed OHCA cases in
      Stockholm County 2000-10 were obtained from the Swedish cardiac arrest register.
      A time-stratified case-crossover design was used to analyse exposure to air
      pollution and the risk of OHCA. Exposure to O3, PM2.5, PM10, NO2, and NOx was
      defined as the mean urban background level during 0-2, 0-24, and 0-72 h before
      the event and control time points. We adjusted for temperature and relative
      humidity. Ozone in urban background was associated with an increased risk of OHCA
      for all time windows. The respective odds ratio (confidence interval) for a 10
      ug/m(3) increase was 1.02 (1.01-1.05) for a 2-h window, 1.04 (1.01-1.07) for 24
      h, and 1.05 (1.01-1.09) for 3 day. The association with 2-h O3 was stronger for
      events that occurred outdoors: 1.13 (1.06-1.21). We observed no effects for other
      pollutants and no effect modification by age, gender, or season. CONCLUSION:
      Short-term exposure to moderate levels of O3 is associated with an increased risk
      of OHCA.

PMID- 24302273
TI  - Efficacy and safety of rivaroxaban compared with warfarin in patients with
      peripheral artery disease and non-valvular atrial fibrillation: insights from
      ROCKET AF.
AB  - AIMS: Vascular disease is included in a risk scoring system to predict stroke in
      patients with non-valvular atrial fibrillation (AF). This post hoc analysis of
      ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the
      relative effectiveness and safety of rivaroxaban vs. warfarin in patients with
      and without peripheral artery disease (PAD). Peripheral artery disease was
      defined on the case-report form as the presences of intermittent claudication,
      amputation for arterial insufficiency, vascular reconstruction, bypass surgery,
      or percutaneous intervention to the extremities, or previously documented
      abdominal aortic aneurysm. METHODS AND RESULTS: ROCKET AF was a double-blind,
      double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for
      the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in
      ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or
      systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non
      major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P =
      0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for
      the prevention of stroke or systemic embolism was similar in patients with PAD
      (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02;
      interaction P = 0.34). There was a significant interaction for major or NMCR
      bleeding in patients with PAD treated with rivaroxaban compared with warfarin
      (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI:
      0.95-1.11; interaction P = 0.037). CONCLUSION: Patients with PAD in ROCKET AF did
      not have a statistically significant higher risk of stroke or systemic embolism
      than patients without PAD, and there were similar efficacy outcomes in patients
      treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk
      of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin
      (interaction P = 0.037). Further investigation is warranted to validate this
      subgroup analysis and determine the optimal treatment in this high-risk cohort of
      AF patients with PAD.

PMID- 24302274
TI  - Mitral cleft repair by mitraclipping.

PMID- 24302275
TI  - Triple antithrombotic therapy in cardiac patients: more questions than answers.
AB  - Many cardiac patients require combined antithrombotic therapy consisting of an
      anticoagulant and inhibition of platelet function. The most frequent indications
      are atrial fibrillation (AF) in combination with drug-eluting stent implantation
      and/or the presence of an acute coronary syndrome (ACS). Currently, the optimal
      combination of anticoagulants and anti-platelet therapy is unknown, but it is
      well established that the combination of regular doses and regimens as prescribed
      in AF or after ACS results in increased bleeding rates. In this review, we
      discuss the current literature and describe approaches to reduce the risk of
      bleeding hoping not to increase the rate of ischaemic events. 

PMID- 24302276
TI  - Mode-specific vibrational relaxation of photoexcited guanosine 5'-monophosphate
      and its acid form: a femtosecond broadband mid-IR transient absorption and
      theoretical study.
AB  - UV-pump/broadband-mid-IR-probe transient absorption (TA) experiments and ab
      initio quantum mechanical (QM) calculations were used to investigate the
      photophysics in heavy water of the neutral and acid forms of guanosine 5'
      monophosphate (GMP and GMPD(+), respectively). Excited GMP undergoes ultrafast
      internal conversion (IC) and returns to the electronic ground state in less than
      one picosecond with a large amount of excess vibrational energy. The
      spectroscopic signals are dominated by vibrational cooling - a process in which
      the solute dissipates vibrational energy to the solvent. For neutral GMP, cooling
      proceeds with a time constant of 3 ps. Following IC, at least some medium
      frequency modes such as the carbonyl stretch and an in-plane ring vibration are
      excited, suggesting that the vibrational energy distribution is non-statistical.
      This is consistent with predicted structural changes upon passage through the
      S1/S0 conical intersection. GMPD(+) differs from GMP by a single deuteron at the
      N7 position, but has a dramatically longer lifetime of 200 ps. Vibrational
      cooling of the S1 state of GMPD(+) was monitored via several medium-frequency
      modes that were assigned using QM calculations. These medium-frequency modes are
      also vibrationally excited in a non-statistical fashion. Excitation of these
      modes is in line with the change in geometry at the S1 minimum of GMPD(+)
      predicted by QM calculations. Furthermore, these modes relax at different rates,
      fully consistent with QM calculations, which predict that excited vibrational
      states of the carbonyl stretch couple strongly to the D2O solvent and thus
      deactivate via intermolecular energy transfer (IET). In contrast, the ring
      stretch couples strongly to other ring modes of the guanine chromophore and
      appears to decay via intramolecular vibrational energy redistribution (IVR). 

PMID- 24302281
TI  - Professor Maurice Staquet, MD, MS (1930 - 2013).

PMID- 24302282
TI  - Medical statistics--a subject of increasing breadth and importance. Preface.

PMID- 24302283
TI  - Comments on 'Estimation in AB/BA crossover trials with application to
      bioequivalence studies with incomplete and complete data designs'.

PMID- 24302284
TI  - Authors' reply to Comments on 'Estimation in AB/BA crossover trials with
      application to bioequivalence studies with incomplete and complete data designs".

PMID- 24302285
TI  - Data governance requirements for distributed clinical research networks:
      triangulating perspectives of diverse stakeholders.
AB  - There is currently limited information on best practices for the development of
      governance requirements for distributed research networks (DRNs), an emerging
      model that promotes clinical data reuse and improves timeliness of comparative
      effectiveness research. Much of the existing information is based on a single
      type of stakeholder such as researchers or administrators. This paper reports on
      a triangulated approach to developing DRN data governance requirements based on a
      combination of policy analysis with experts, interviews with institutional
      leaders, and patient focus groups. This approach is illustrated with an example
      from the Scalable National Network for Effectiveness Research, which resulted in
      91 requirements. These requirements were analyzed against the Fair Information
      Practice Principles (FIPPs) and Health Insurance Portability and Accountability
      Act (HIPAA) protected versus non-protected health information. The requirements
      addressed all FIPPs, showing how a DRN's technical infrastructure is able to
      fulfill HIPAA regulations, protect privacy, and provide a trustworthy platform
      for research. 

PMID- 24302286
TI  - Integrating pharmacogenetic information and clinical decision support into the
      electronic health record.
AB  - Pharmacogenetics (PG) examines gene variations for drug disposition, response, or
      toxicity. At the National Institutes of Health Clinical Center (NIH CC), a
      multidepartment Pharmacogenetics Testing Implementation Committee (PGTIC) was
      established to develop clinical decision support (CDS) algorithms for abacavir,
      carbamazepine, and allopurinol, medications for which human leukocyte antigen
      (HLA) variants predict severe hypersensitivity reactions. Providing PG CDS in the
      electronic health record (EHR) during order entry could prevent adverse drug
      events. Medical Logic Module (MLM) programming was used to implement PG CDS in
      our EHR. The MLM checks to see if an HLA sequence-based gene test is ordered. A
      message regarding test status (result present, absent, pending, or test not
      ordered) is displayed on the order form, and the MLM determines if the prescriber
      can place the order, place it but require an over-ride reason, or be blocked from
      placing the order. Since implementation, more than 725 medication orders have
      been placed for over 230 patients by 154 different prescribers for the three
      drugs included in our PG program. Prescribers commonly used an over-ride reason
      when placing the order mainly because patients had been receiving the drug
      without reaction before implementation of the CDS program. Successful
      incorporation of PG CDS into the NIH CC EHR required a coordinated,
      interdisciplinary effort to ensure smooth activation and a positive effect on
      patient care. Prescribers have adapted to using the CDS and have ordered PG
      testing as a direct result of the implementation. 

PMID- 24302287
TI  - Assessment of flower number per inflorescence in grapevine by image analysis
      under field conditions.
AB  - BACKGROUND: Flowers, flowering and fruit set are key determinants of grapevine
      yield. Currently, practical methods to assess the flower number per
      inflorescence, necessary for fruit set estimation, are time and labour demanding.
      This work aims at developing a simple, cheap, fast, accurate and robust machine
      vision methodology to be applied to RGB images taken under field conditions, to
      estimate the number of flowers per inflorescence automatically. RESULTS: Ninety
      images of individual inflorescences of Vitis vinifera L. cultivars Tempranillo,
      Graciano and Carignan were acquired in the vineyard with a pocket RGB camera
      prior to flowering, and used to develop and test the 'flower counting' algorithm.
      Strong and significant relationships, with R(2) above 80% for the three cultivars
      were observed between actual and automated estimation of inflorescence flower
      numbers, with a precision exceeding 90% for all cultivars. CONCLUSION: The
      developed algorithm proved that the analysis of digital images captured by pocket
      cameras under uncontrolled outdoors conditions was able to automatically provide
      a useful estimation of the number of flowers per inflorescence of grapevines at
      early stages of flowering.

PMID- 24302288
TI  - Spectrin: structure, function and disease.
AB  - Spectrin is a large, cytoskeletal, and heterodimeric protein composed of modular
      structure of alpha and beta subunits, it typically contains 106 contiguous amino
      acid sequence motifs called "spectrin repeats". Spectrin is crucial for
      maintaining the stability and structure of the cell membrane and the shape of a
      cell. Moreover, it contributes to diverse cell functions such as cell adhesion,
      cell spreading, and the cell cycle. Mutations of spectrin lead to various human
      diseases such as hereditary hemolytic anemia, type 5 spinocerebellar ataxia,
      cancer, as well as others. This review focuses on recent advances in determining
      the structure and function of spectrin as well as its role in disease. 

PMID- 24302289
TI  - EDdb: a web resource for eating disorder and its application to identify an
      extended adipocytokine signaling pathway related to eating disorder.
AB  - Eating disorder is a group of physiological and psychological disorders affecting
      approximately 1% of the female population worldwide. Although the genetic
      epidemiology of eating disorder is becoming increasingly clear with accumulated
      studies, the underlying molecular mechanisms are still unclear. Recently,
      integration of various high-throughput data expanded the range of candidate genes
      and started to generate hypotheses for understanding potential pathogenesis in
      complex diseases. This article presents EDdb (Eating Disorder database), the
      first evidence-based gene resource for eating disorder. Fifty-nine experimentally
      validated genes from the literature in relation to eating disorder were collected
      as the core dataset. Another four datasets with 2824 candidate genes across 601
      genome regions were expanded based on the core dataset using different criteria
      (e.g., protein-protein interactions, shared cytobands, and related complex
      diseases). Based on human protein-protein interaction data, we reconstructed a
      potential molecular sub-network related to eating disorder. Furthermore, with an
      integrative pathway enrichment analysis of genes in EDdb, we identified an
      extended adipocytokine signaling pathway in eating disorder. Three genes in EDdb
      (ADIPO (adiponectin), TNF (tumor necrosis factor) and NR3C1 (nuclear receptor
      subfamily 3, group C, member 1)) link the KEGG (Kyoto Encyclopedia of Genes and
      Genomes) "adipocytokine signaling pathway" with the BioCarta "visceral fat
      deposits and the metabolic syndrome" pathway to form a joint pathway. In total,
      the joint pathway contains 43 genes, among which 39 genes are related to eating
      disorder. As the first comprehensive gene resource for eating disorder, EDdb (
      http://eddb.cbi.pku.edu.cn ) enables the exploration of gene-disease
      relationships and cross-talk mechanisms between related disorders. Through
      pathway statistical studies, we revealed that abnormal body weight caused by
      eating disorder and obesity may both be related to dysregulation of the novel
      joint pathway of adipocytokine signaling. In addition, this joint pathway may be
      the common pathway for body weight regulation in complex human diseases related
      to unhealthy lifestyle. 

PMID- 24302290
TI  - DNA methylation polymorphism and stability in Chinese indica hybrid rice.
AB  - Conventional rice breeding has long focused on exploiting the DNA sequence
      diversity. However, epigenetic diversity, reflected particularly in DNA
      methylation, can also contribute to phenotypic variation and should not be
      overlooked in rice breeding. In this study, 20 parental lines of indica rice,
      which are widely used in hybrid rice breeding in China, were analyzed to
      investigate variations of DNA methylation and its inheritance. The results
      revealed a wide diversity in DNA methylation among these breeding lines. A
      positive correlation was seen between DNA methylation and genetic diversity.
      Furthermore, some of the methylated DNA was inherited in the subsequent
      generation, regardless of whether they were produced by selfing or hybrid
      crossing. This study provides insight into the methylation patterns in rice, and
      suggests the importance of epigenetic diversity in rice breeding. 

PMID- 24302291
TI  - TinII intron, an enhancer to affect the function of the cytoplasmic male
      sterility related gene T in Brassica juncea.
AB  - The T gene, which was cloned from the mitochondria of tumorous stem mustard
      (Brassica juncea var. tumida), is a cytoplasmic male sterility (CMS)-related gene
      that can produce two transcripts, T1170 and T1243. The latter is transcribed with
      the uncleaved intron TinII. In our previous study, transgenic Arabidopsis
      thaliana plants over-expressing the T1243 transcript (OE-T1243) showed a severe
      male-sterile phenotype, whereas OE-T1170 plants did not. However, the functional
      mechanism of the T gene in B. Juncea remained unknown. In this study, microscopic
      analyses of paraffin sections of anthers confirmed that OE-T1243 plants did not
      produce normal pollen, whereas OE-T1170 plants did. We analyzed the transcription
      of 15 anther development-related genes and found that transcript levels of
      nozzle/sporocyteless and barely any meristem 1 and 2 were markedly lower in OE
      T1243 plants than those in wild type, while the transcript levels of these genes
      in OE-T1170 plants were unchanged. To investigate the potential roles of TinII,
      we inserted the TinII sequence upstream of a minimal region (-60) of the
      cauliflower mosaic virus 35S promoter fused to the 5' end of the beta
      glucuronidase (GUS) reporter gene. Analysis of the transgenic plants suggested
      that TinII acted as an enhancer to significantly increase GUS expression. The
      potential action mechanism is that the TinII intron acts as an enhancer to affect
      the function of the CMS-related gene T. 

PMID- 24302292
TI  - Knockdown of OsHox33, a member of the class III homeodomain-leucine zipper gene
      family, accelerates leaf senescence in rice.
AB  - The class III homeodomain-leucine zipper (HD-Zip III) gene family plays important
      roles in plant growth and development, including regulation of apical embryo
      patterning, embryonic shoot meristem formation, leaf polarity, vascular
      development, and meristem function, with a particularly crucial function in leaf
      development. Although HD-Zip III members are highly conserved in land plants,
      previous studies, such as genetic analyses based on multiple mutants in
      Arabidopsis and other plants, suggest that various HD-Zip III family genes have
      evolved with distinct functions and pleiotropic effects on plant growth and
      development. In this study, we analyzed a HD-Zip III member, OsHox33, and
      demonstrated that it plays an important role in age-dependent leaf senescence in
      rice. We constructed two specific RNAi vectors derived from the 5'-end region and
      3'-UTR of OsHox33 to knockdown its expression. Transgenic plants harboring either
      RNAi construct displayed similar phenotypes of precocious leaf senescence
      symptoms, suggesting that knockdown of OsHox33 accelerates leaf senescence in
      rice. pOsHox33::GUS fusion expression and RT-PCR revealed that OsHox33 is highly
      expressed in young organs, especially in young meristems such as shoot apical
      meristems, intercalary meristems, and young callus. In addition, real-time PCR
      indicated that OsHox33 was more highly expressed in young leaves than in old
      leaves. To further investigate OsHox33 function, we analyzed chloroplast
      ultrastructure in different-aged leaves of RNAi plants, and found that OsHox33
      knockdown accelerated chloroplast degradation, which is consistent with RNAi
      phenotypes. Finally, real-time PCR studies showed that OsHox33 can regulate the
      expression of GS1 and GS2, two senescence-associated genes. Taken together, the
      work presented here provides new insights into the function of HD-Zip III members
      in plants. 

PMID- 24302293
TI  - A cellular response protein induced during HSV-1 infection inhibits viral
      replication by interacting with ATF5.
AB  - Studies of herpes simplex virus type 1 (HSV-1) infection have shown that many
      known and unknown cellular molecules involved in viral proliferation are up
      regulated following HSV-1 infection. In this study, using two-dimensional
      polyacrylamide gel electrophoresis, we found that the expression of the HSV-1
      infection response repressive protein (HIRRP, GI 16552881) was up-regulated in
      human L02 cells infected with HSV-1. HIRRP, an unknown protein, was initially
      localized in the cytoplasm and then translocated into the nucleus of HSV-1
      infected cells. Further analysis showed that HIRRP represses HSV-1 proliferation
      by inhibiting transcription of the viral genome by interacting with the cellular
      transcription factor, ATF5, via its N-terminal domain. ATF5 represses the
      transcription of many host genes but can also act as an activator of genes
      containing a specific motif. We found that ATF5 promotes the proliferation of HSV
      1 via a potential mechanism by which ATF5 enhances the transcription of viral
      genes during the course of an HSV-1 infection; HIRRP then induces feedback
      repression of this transcription by interacting with ATF5. 

PMID- 24302294
TI  - Improved picoliter-sized micro-reactors for high-throughput biological analysis.
AB  - High-throughput pyrosequencing, carried out in millions of picoliter-sized
      reactors on a fiber-optic slide, is known for its longer read length. However,
      both optical crosstalk (which reduces the signal-to-noise ratio of CCD images)
      and chemical retention adversely affect the accuracy of chemiluminescence
      determination, and ultimately decrease the read length and the accuracy of
      pyrosequencing results. In this study, both titanium and oxidized aluminum films
      were deposited on the side walls and upper faces of micro-reactor slides to
      enhance optical isolation; the films reduced the inter-well crosstalk by one
      order of magnitude. Subsequently, chemical retention was shown to be caused by
      the lower diffusion coefficient of the side walls of the picoliter-sized reactors
      because of surface roughness and random pores. Optically isolated fiber-optic
      slides over-coated with silicon oxide showed smoother surface morphology,
      resulting in little chemical retention; this was further confirmed with
      theoretical calculations. Picoliter-sized micro-reactors coated with titanium
      silicon oxide films showed the least inter-well optical crosstalk and chemical
      retention; these properties are expected to greatly improve the high-throughput
      pyrosequencing performance. 

PMID- 24302295
TI  - A brief review on studies of Alzheimer's disease in China: its mechanism, imaging
      and therapy.

PMID- 24302296
TI  - Establishment of a highly efficient hematopoietic differentiation model from
      human embryonic stem cells for functional screening.

PMID- 24302298
TI  - Laser speckle contrast analysis for quantifying the Allen test: a feasibility
      study.
AB  - BACKGROUND AND OBJECTIVE: The radial artery has become a routinely used conduit
      for coronary artery bypass graft surgery (CABG). Prior to surgery the Allen test
      is performed to test the patency of the ulnar artery. A positive Allen test,
      reperfusion >5 seconds, suggests an insufficient perfusion of the hand by the
      ulnar artery. In this study we investigated if laser speckle contrast analysis
      (LASCA) provides an objective determination of the reperfusion time. MATERIALS
      AND METHODS: When the hand is illuminated with coherent laser light, the
      backscattered light will result in an interference pattern consisting of bright
      and dark areas called speckles. This speckle pattern will change due to movement
      of red blood cells. LASCA uses these changes to visualize the perfusion during
      the Allen test. Reperfusion is measured on the palmar side of the hand. The
      reperfusion time is defined as the time from onset of reperfusion to maximum
      perfusion calculated by a polynomial curve fit. The reperfusion time of the hand
      of patients undergoing CABG (n = 30) is measured using LASCA and is compared to
      the conventional Allen test performed by the nurse practitioner. RESULTS: LASCA
      measurements showed a negative Allen test of both hands of 16 patients. Fourteen
      had a borderline reperfusion time of 5-6 seconds and/or a positive Allen test of
      one or both hands. No statistical significant difference was observed for the
      LASCA Allen test compared to the conventional Allen test, P = 0.549 for the left
      hand and P = 0.223 for the right hand. CONCLUSION: LASCA is able to visualize
      perfusion of the hand and measure a quick, moderate, slow reperfusion response or
      no reperfusion. It is technically feasible to determine the reperfusion time of
      the hand. LASCA can be a useful and objective tool to assess ulnar collateral
      blood supply to the hand prior to harvesting of the radial artery as a bypass
      graft.

PMID- 24302300
TI  - Effect of configuration of 2-vinyldiazocarbonyl compounds on their reactivity:
      experimental and computational study.
AB  - Non-fluorinated vinyldiazo compounds with trans-configuration irrespective of the
      nature of 3-R(1)-substituent (R(1) = H, Me, TBSO) even under ambient conditions
      easily cyclize to produce pyrazoles, while cis-stereoisomers undergo similar ring
      closure only at elevated temperatures or decompose to produce vinyloxocarbene
      reaction products. The 3-CF3-substituted analogues with cis- or trans
      configuration do not produce pyrazoles at all, but on heating furnish only
      vinylcarbene derived products. DFT calculations of theoretical energy barriers
      adequately explain the different experimental reactivity found for stereoisomeric
      vinyldiazocarbonyl compounds, and a new model for their interconversion through
      the corresponding pyrazoles has been suggested. 

PMID- 24302299
TI  - Medical interventions for traumatic hyphema.
AB  - BACKGROUND: Traumatic hyphema is the entry of blood into the anterior chamber
      (the space between the cornea and iris) subsequent to a blow or a projectile
      striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated
      trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma,
      optic atrophy, etc.) may seriously affect vision. Such complications may lead to
      permanent impairment of vision. Patients with sickle cell trait/disease may be
      particularly susceptible to increases of elevated intraocular pressure. If
      rebleeding occurs, the rates and severity of complications increase. OBJECTIVES:
      To assess the effectiveness of various medical interventions in the management of
      traumatic hyphema. SEARCH METHODS: We searched CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue
      8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid
      MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January
      1980 to August 2013), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the
      WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 30 August 2013. SELECTION CRITERIA: Two authors independently assessed the
      titles and abstracts of all reports identified by the electronic and manual
      searches. In this review, we included randomized and quasi-randomized trials that
      compared various medical interventions versus other medical interventions or
      control groups for the treatment of traumatic hyphema following closed globe
      trauma. We applied no restrictions regarding age, gender, severity of the closed
      globe trauma, or level of visual acuity at the time of enrolment. DATA COLLECTION
      AND ANALYSIS: Two authors independently extracted the data for the primary and
      secondary outcomes. We entered and analyzed data using Review Manager 5. We
      performed meta-analyses using a fixed-effect model and reported dichotomous
      outcomes as odds ratios and continuous outcomes as mean differences. MAIN
      RESULTS: We included 20 randomized and seven quasi-randomized studies with 2643
      participants in this review. Interventions included antifibrinolytic agents (oral
      and systemic aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid),
      corticosteroids (systemic and topical), cycloplegics, miotics, aspirin,
      conjugated estrogens, traditional Chinese medicine, monocular versus bilateral
      patching, elevation of the head, and bed rest. No intervention had a significant
      effect on visual acuity whether measured at two weeks or less after the trauma or
      at longer time periods. The number of days for the primary hyphema to resolve
      appeared to be longer with the use of aminocaproic acid compared with no use, but
      was not altered by any other intervention.Systemic aminocaproic acid reduced the
      rate of recurrent hemorrhage (odds ratio (OR) 0.25, 95% confidence interval (CI)
      0.11 to 0.57), but a sensitivity analysis omitting studies not using an intention
      to-treat (ITT) analysis reduced the strength of the evidence (OR 0.41, 95% CI
      0.16 to 1.09). We obtained similar results for topical aminocaproic acid (OR
      0.42, 95% CI 0.16 to 1.10). We found tranexamic acid had a significant effect in
      reducing the rate of secondary hemorrhage (OR 0.25, 95% CI 0.13 to 0.49), as did
      aminomethylbenzoic acid as reported in one study (OR 0.07, 95% CI 0.01 to 0.32).
      The evidence to support an associated reduction in the risk of complications from
      secondary hemorrhage (i.e. corneal bloodstaining, peripheral anterior synechiae,
      elevated intraocular pressure, and development of optic atrophy) by
      antifibrinolytics was limited by the small number of these events. Use of
      aminocaproic acid was associated with increased nausea, vomiting, and other
      adverse events compared with placebo. We found no difference in the number of
      adverse events with the use of systemic versus topical aminocaproic acid or with
      standard versus lower drug dose. The available evidence on usage of
      corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to
      the small numbers of participants and events in the trials.We found no difference
      in effect between a single versus binocular patch or ambulation versus complete
      bed rest on the risk of secondary hemorrhage or time to rebleed. AUTHORS'
      CONCLUSIONS: Traumatic hyphema in the absence of other intraocular injuries
      uncommonly leads to permanent loss of vision. Complications resulting from
      secondary hemorrhage could lead to permanent impairment of vision, especially in
      patients with sickle cell trait/disease. We found no evidence to show an effect
      on visual acuity by any of the interventions evaluated in this review. Although
      evidence was limited, it appears that patients with traumatic hyphema who receive
      aminocaproic acid or tranexamic acid are less likely to experience secondary
      hemorrhaging. However, hyphema in patients treated with aminocaproic acid take
      longer to clear.Other than the possible benefits of antifibrinolytic usage to
      reduce the rate of secondary hemorrhage, the decision to use corticosteroids,
      cycloplegics, or nondrug interventions (such as binocular patching, bed rest, or
      head elevation) should remain individualized because no solid scientific evidence
      supports a benefit. As these multiple interventions are rarely used in isolation,
      further research to assess the additive effect of these interventions might be of
      value.

PMID- 24302301
TI  - Abscisic acid induction of cloned cotton late embryogenesis-abundant (Lea) mRNAs.
AB  - Earlier studies found that cotton (Gossypium hirsutum L.) cotyledons contain
      several mRNAs which are more abundant during late embryogenesis than in mid
      embryogenesis or early germination. They are here termed 'Late embryogenesis
      abundant' mRNAs, encoded by Lea loci. Complementary DNA clones for 18 such mRNA
      sequences, defined at a hybridization criterion of Tm-15 degrees C, were
      identified in a mature embryo cDNA library by differential cDNA hybridization. At
      a lower hybridization criterion, some sequence homology was found within several
      of these cloned Lea mRNA sequences. Each Lea mRNA sequence comprises 0.04-1.3% of
      mature embryo poly(A)(+) mRNA, a level ten-fold to several hundred-fold higher
      than in young embryo or 24 h seedling poly(A)(+) mRNA. Of 18 Lea mRNA sequences
      examined in cultured young embryos, the level of at least 13 are specifically
      increased by exogenous abscisic acid (ABA), several to a level near that in
      normal mature embryos. However, the abundance of several of the sequences does
      not appear to be significantly modulated by ABA. The LEA polypeptides encoded by
      10 Lea mRNA sequences were identified by hybrid-arrested translation. They
      include most of the late embryogenesis-abundant, ABA-inducible, polypeptides
      previously identified. Preliminary results suggest that many of the individual
      Lea mRNA sequences are transcribed from 1-3 genes in each of cotton's two
      subgenomes. 

PMID- 24302302
TI  - Bleomycin resistance: a new dominant selectable marker for plant cell
      transformation.
AB  - Plant cells are sensitive to the antibiotic bleomycin, a DNA damaging
      glycopeptide. A bleomycin resistance determinant, located on transposon Tn5 and
      functional in bacteria, has been cloned in a plant expression vector and
      introduced into Nicotiana plumbaginifolia using Agrobacterium tumefaciens. The
      expression of this determinant in plant cells confers resistance to bleomycin and
      allows selection of transformed plant cells. 

PMID- 24302303
TI  - Conservation of IS66 homologue of octopine Ti plasmid DNA in Rhizobium fredii
      plasmid DNA.
AB  - DNA sequences homologous to the T-DNA region of the octopine Ti plasmid from
      Agrobacterium tumefaciens are found in various fast-growing Rhizobium fredii
      strains. The largest fragment (BamHI fragment 2) at the right-boundary region of
      the 'core' T-DNA hybridizes to more than one plasmid present in R. fredii.
      However, one smaller fragment (EcoRI fragment 19a) adjacent to the 'core' T-DNA
      shows homology only with the plasmid carrying the symbiotic nitrogen-fixation
      genes (pSym). Hybridization data obtained with digested R. fredii USDA193 pSym
      DNA suggests that the homology is mainly with two HindIII fragments, 1.7 kb and
      8.8 kb in size, of the plasmid. The 1.7 kb HindIII fragment also hybridizes to
      two regions of the virulence plasmid of A. tumefaciens, pAL1819, a deletion
      plasmid derived from the octopine Ti plasmid, pTiAch5. Hybridization studies with
      an insertion element IS66 from A. tumefaciens indicate that the 1.7 kb HindIII
      fragment of R. fredii plasmid, homologous to the T-DNA and the virulence region
      of Ti plasmid, is itself an IS66 homologue. 

PMID- 24302304
TI  - Expression of nodule-specific glutamine synthetase genes during nodule
      development in soybeans.
AB  - A cDNA clone (pcPvNGS-01) to glutamine synthetase (GS) mRNA from root nodules of
      Phaseolus vulgaris showed cross-hybridization to GS and mRNA from soybean root
      nodules, thus allowing its use as a probe to study the expression of GS genes
      during root nodule development in soybeans. Hybrid-select translation of root and
      nodule RNA of soybean with DNA from pcPvNGS-01, followed by 2D gel
      electrophoresis, showed six peptides in the root and an additional four peptides
      in the nodule which represent nodule-specific glutamine synthetase (GSn) gene
      products. The GSn gene products appeared for the first time between day 11 and 12
      after infection, either concomitant with the onset of nitrogenase activity or
      immediately following it. The levels of expression of the GSn and leghemoglobin
      genes were not affected in young Fix(-) nodules formed by Bradyrhizobium
      japonicum strains that are defective in nitrogenase activity, suggesting that the
      induction of these two sets of host genes take place independent of nitrogenase
      activity. However, in Fix(-) nodules that are incapable of maintaining the
      peribacteroid membrane, GSn gene products were not detected while 1ba, 1bc2 and
      1bc3 appeared. In both the timing of appearance during root nodule development
      and the effect of different bacterial mutations on the expression, GSn genes
      differ from most other nodulin genes examined (30), suggesting different
      regulatory mechanisms. 

PMID- 24302305
TI  - Restriction fragment map of sugar beet (Beta vulgaris L.) chloroplast DNA.
AB  - A restriction endonuclease fragment map of sugar beet chloroplast DNA (ctDNA) has
      been constructed with the enzymes SmaI, PstI and PvuII. The ctDNA was found to be
      contained in a circular molecule of 148.5 kbp. In common with many other higher
      plant ctDNAs, sugar beet ctDNA consists of two inverted repeat sequences of about
      20.5 kbp separated by two single-copy regions of different sizes (about 23.2 and
      84.3 kbp). Southern hybridization analyses indicated that the genes for rRNAs
      (23S+16S) and the large subunit of ribulose 1,5-bisphosphate carboxylase were
      located in the inverted repeats and the large single-copy regions, respectively. 

PMID- 24302306
TI  - The sequences of two nuclear genes and a pseudogene for tRNA(Pro) from the higher
      plant Phaseolus vulgaris.
AB  - A genomic bank of nuclear DNA (nDNA) from the higher plant Phaseolus vulgaris,
      constructed using the lambda EMBL-4 vector, has been screened for the presence of
      tRNA genes. One of the many positive recombinants was found to hybridise several
      times stronger than the other positives, and has been shown to contain several
      tRNA genes. We report the structure of two nuclear tRNA genes for tRNA(Pro),
      namely tRNA(Pro)(UGG) and tRNA(Pro)(AGG), and that of a 'pseudogene' for
      tRNA(Pro). This 'pseudogene', despite showing 95% homology with the other
      tRNA(Pro) species presented here, has several features which are likely to affect
      its transcription or its functioning as a tRNA. 

PMID- 24302307
TI  - Amino acid sequence of the ribulose-1,5-bisphosphate carboxylase/oxygenase small
      subunit from Euglena.
AB  - The amino acid sequence of the ribulose-1,5-bisphosphate carboxylase/oxygenase
      (RuBisCO) small subunit (SSU) from Euglena has been established by alignment of
      the sequence of peptides obtained by cleavage with chymotrypsin, trypsin,
      Staphylococcus aureus protease or formic acid. The Euglena SSU has 138 amino
      acids and thus represents longest SSU sequence described so far. Homology is only
      41% with cyanobacteria SSU and about 51% with higher plant SSU, whereas it is
      around 75% between higher plants. The largest homologous portion between all the
      known SSU sequences is localized in the second half and covers about 20 amino
      acids. The phylogenetic tree based on known SSU sequences has been established
      and the rate of amino acid substitution for SSU is estimated to be about 1.35*10(
      9) per year and per site. Despite heterogeneity in amino acid sequence, we found
      that the overall secondary structure is fairly well conserved. 

PMID- 24302309
TI  - Biotechnology news and views.

PMID- 24302308
TI  - The localization of genes for ribosomal, cytochrome b6/f complex and photosystems
      I and II polypeptides on the chloroplast chromosome of Vicia faba.
AB  - Detailed studies of rearranged chloroplast genomes such as Vicia faba should give
      insights into the constraints governing the positional organization of the
      various gene clusters on the chloroplast chromosome. Seven polypeptide genes have
      already been mapped on the Vicia faba chloroplast genome (21, 22). In this
      report, ten additional chloroplast DNA-coded polypeptide genes have been mapped
      by heterologous hybridization. These genes include cytochrome b6 and subunit 4 of
      the cytochrome b6/f complex, the two P700 chlorophyll a apoproteins of
      photosystem I, the two chlorophyll a-binding proteins of photosystem II,
      cytochrome b559, the D2 polypeptide and two ribosomal proteins. The direction of
      transcription for five of these gene sequences has been established by utilizing
      5' and 3' end specific gene probes. The genetic organization of the Vicia faba
      chloroplast genome was compared with the chloroplast maps of the standard
      conserved genome of spinach and the more rearranged genome of pea. 

PMID- 24302310
TI  - Hormonal control of tobacco protoplast nucleic acid metabolism during in vitro
      culture.
AB  - Tobacco mesophyll protoplasts cultivated in vitro do not synthesize a measurable
      quantity of chloroplastic ribosomal RNA, but actively synthesize cytoplasmic
      ribosomal RNA, polyadenylated RNA, and proteins. These syntheses are essentially
      independent of the presence of hormones in the culture medium and are thus
      related to the ageing phenomenon induced by isolation from the plant and in-vitro
      culture. At all stages of culture and in all culture media, protoplasts
      incorporate low levels of thymidine into their DNA. However, the incorporation of
      considerable quantities of thymidine, indicative of the S phase, only takes place
      after 25-30 h and requires the presence of auxin and cytokinin. 

PMID- 24302311
TI  - Uptake and efflux of inorganic carbon in Dunaliella salina.
AB  - The apparent photosynthetic Km (CO2) of air-grown Dunaliella salina is 2 MUM as
      measured both by the filtering centrifugation technique and by O2 electrode.
      These cells are capable of accumulating inorganic carbon (Cinorg) up to 20 times
      its concentration in the medium. It is suggested that air-grown Dunaliella cells
      are able to concentrate CO2 within the cell. Analysis of the efflux of Cinorg
      from cells previously loaded with H(14)CO 3 (-) demonstrated the existence of an
      internal pool which has an half-time of depletion of 2.5-7 min depending on the
      conditions of the experiment. This finding indicates that the internal Cinorg
      pool is not readily exchangeable with the external medium. Furthermore, the
      influence of the presence or absence of unlabelled Cinorg in the medium during
      the efflux experiment on the half-time observed indicate that efflux of Cinorg is
      not a simple diffusion process but is rather carrier-mediated. 

PMID- 24302312
TI  - The action of specific inhibitors of auxin transport on uptake of auxin and
      binding of N-1-naphthylphthalamic acid to a membrane site in maize coleoptiles.
AB  - Using both 1-mm segments of corn (Zea mays L.) coleoptiles and a preparation of
      membranes isolated from the same source, we have compared the effectiveness of
      several inhibitors of geotropism and polar transport in stimulating uptake of
      auxin (indole-3-acetic acid, IAA) into the tissue and in competing with N-1
      naphthylphthalamic acid (NPA) for a membrane-bound site. Low concentrations of
      2,3,5-triiodobenzoic acid (TIBA), NPA, 2-chloro-9-hydroxyfluorene-9-carboxylic
      acid (morphactin), and fluorescein, eosin, and mercurochrome all stimulated net
      uptake of [(3)H]IAA by corn coleoptile tissues while higher concentrations
      reduced the uptake of both [(3)H]IAA and another lipophilic weak acid,
      [(14)C]benzoic acid. Since low concentrations of fluorescein and its derivatives
      competed for the same membrane-bound site in vitro as did morphactin and NPA, the
      basis for both the specific stimulation of auxin accumulation and the inhibition
      of polar auxin transport by all these compounds may be their ability to interfere
      with the carrier-mediated efflux of auxin anions from cells. At higher
      concentrations, the decrease in accumulation of weak acids was nonspecific and
      thus may be the result of acidification of the cytoplasm and a general decrease
      in the driving force for uptake of the weak acids. Triiodobenzoic acid was an
      exception. Low concentration of TIBA (0.1-1 MUM) were much less effective than
      NPA in competing for the NPA receptor in vitro, but little different from NPA in
      ability to stimulate auxin uptake. One possibility is that TIBA, a substance
      which is polarly transported, may compete with auxin for the polar transport site
      while NPA, morphactin, and the fluorescein derivatives may render this site
      inactive. 

PMID- 24302313
TI  - Membrane organization in soybean seeds during hydration.
AB  - The ability of seeds to withstand dehydration indicates that their membranes may
      maintain structural integrity even when dry. Analysis of polar lipids (the
      principal lipidic constituents of the membranes) from soybean seeds (Glycine-max
      (L.) Merr.) by X-ray diffraction indicated that even in the dehydrated state the
      lipids retained a lamellar (bilayer) configuration. As the degree of hydration
      was raised, evidence of some structural alteration (apparent as an abrupt
      increase in bilayer spacing) was obtained from diffraction patterns of both the
      extracted lipid and particles of seed tissue. In seed tissue this increase in
      bilayer spacing occurred at a hydration level just above that at which free water
      could be detected by nuclear-magnetic-resonance analysis. The water content at
      which the increase in bilayer spacing occurred was higher in the seed tissue than
      in the extracted polar lipids, probably because other cell components restricted
      the availability of free water in the seed. 

PMID- 24302314
TI  - Subculture-induced protein synthesis in tissue cultures of Glycine max and
      Phaseolus vulgaris.
AB  - The effects of subculture of tissue cultures on the levels of certain mRNAs have
      been investigated, and the action of cytokinins on the disposition of certain
      mRNAs between possible non-translating and translating pools has been determined.
      mRNA preparations were assayed by cell free translation with message-dependent
      reticulocyte lysate and the in vitro products resolved by polyacrylamide gel
      electrophoresis. Subculture of the cells caused a rapid stimulation of polysome
      formation. It also increased the translatable levels of a small group of mRNAs,
      one of which was present in both bean and soybean cultures. Cytokinins caused a
      slight increase in polysome levels after subculture, but had no effect on the
      levels of particular mRNAs, nor on the distribution of mRNAs between a non
      translating and translating pool, nor on polysome levels in the absence of
      subculture. 

PMID- 24302315
TI  - Some rapid effects of synthetic auxins on mRNA levels in cultured plant cells.
AB  - When bean and soybean tissue culture cells were subcultured into fresh medium the
      translatable levels of a small group of mRNAs increased rapidly and then
      decreased to a low level 10 h after subculture. By starving the cells of auxin
      and then subculturing them into media with or without auxin, it was found that
      the increase in translatable mRNA for certain proteins was strongly dependent on
      auxins. The rapidity of this effect suggested that auxins can directly modulate
      the possible transcription of certain mRNA molecules. 

PMID- 24302316
TI  - Oleosomes in flag leaves of wheat; their distribution, composition and fate
      during senesence and rust-infection.
AB  - Oleosomes, up to 14MUm in diameter, were found in mesophyll and bundle sheath
      cells of the flag and lower leaves of wheat cv Professeur Marchal. They develop
      in flag leaves at least 10 d before anthesis, possibly from fatty acids secreted
      by the plastids, and persist in mature and senescing leaf tissue. Oleosomes are
      bordered with an osmiophilic layer rather than a unit membrane. The major lipids
      of oleosomes, isolated 20 d after anthesis, are triacylglycerols (50%) and sterol
      or wax exter (34%). The dominant fatty acids of both lipid classes are plamitic
      (16:0) and stearic (18:0) acids which accounts for the low osmiophilia of the
      oleosomes. The function of the oleosomes is unknown but they may act as short
      term energy reserves. Oleosomes persist in leaves infected with brown rust, even
      in cells penetrated by haustoria. Yellowish-brown oleosomes found in senescing
      and rust-infected leaves may be formed by the release and coalescence of
      pigmented plastoglobuli. 

PMID- 24302317
TI  - Comparative analyses of the effect of triacontanol on photosynthesis,
      photorespiration and growth of tomato (C3-plant) and maize (C 4-plant).
AB  - Tomato (C3-plants) and maize (C4-plants) were grown in a nutrient solution to
      which triacontanol was added twice a week. After about 4 weeks the triacontanol
      treatment caused a significant increase in the dry weight of the tomato plants.
      Leaf area and dry weight measurements of tomato leaves at different stages of
      development showed that the largest increase in growth was obtained when
      triacontanol treatment was initiated before bud formation. In maize, no effect of
      the triacontanol treatment on dry wieght was observed. Photosynthesis was
      inhibited by 27% in young leaves from triacontanol-treated tomato plants and 39%
      in the controls, when the oxygen concentration was raised from 2% to 21%. In
      maize no change in photosynthesis could be observed, neither after altered oxygen
      concentration nor after triacontanol treatment. The difference in the response of
      C3- and C4-plants to triacontanol indicates that it regulates processes related
      to photosynthesis. 

PMID- 24302318
TI  - An endogenous rhythm of trap formation in the nematophagous fungus Arthrobotrys
      oligospora.
AB  - In the predacious fungus Arthrobotrys oligospora Fres., the number and
      distribution of traps formed after the addition of living nematodes to the
      colonies were determined. At 21 degrees C the traps were formed periodically; the
      mean period was 42.3+/-0.8 h. The periodicity was independent of light-dark (LD)
      cycles of 24 h (10:14). Temperature influenced the hyphal elongation but did not
      affect the periodic trap formation; at lower temperatures the peaks of trap
      formation were close together, showing partial overlapping. Induction of rhythmic
      mycelial growth and conidiation by chemical means was effective only in LD
      cycles. The latter diurnal rhythm was weakly correlated with the trap formation
      and did not affect the endogenous period of approximately 42 h. 

PMID- 24302319
TI  - Chlorophyll biosynthesis by mesophyll protoplasts and plastids from etiolated oat
      (Avena sativa L.) leaves.
AB  - The uptake of [1-(3)H]geranylgeranyl diphosphate (GGPP) into protoplasts and
      intact etioplasts and the metabolic interconversion therein was studied after a 2
      min pulse of white light. The chlorophyll synthetase reaction, Chlide+GGPP
      >ChlGG, was taken as a natural probe for the etioplast compartment. This reaction
      yields labeled ChLGG and, by hydrogenation, labeled ChlP, when [1-(3)H]GGPP
      receives access to the etioplast stroma. It was found that penetration across the
      plastid envelope was rapid and that penetration across the plasma membrane of
      protoplasts, however, was slow. A cellular pool of soluble GGPP was detected.
      This pool was lost, in part, during preparation of the protoplasts and almost
      completely during preparation of the etioplasts. The membrane-bound phytol pool
      of etioplasts could not be replaced by exogenous [(3)H]GG. The endogenous GG and
      phytol pools of protoplasts, which were larger than those of etioplasts, could be
      replaced in part by exogenous [(3)H]GGPP. That part of this pool exists as
      soluble GGPP or as a direct precursor in the cytoplasm is discussed. 

PMID- 24302320
TI  - Changes in glucan synthetase activity and plasma membrane proteins during
      encystment of the cellular slime mold Polysphondylium pallidum.
AB  - The activity of glucan synthetase increased dramatically during encystment of
      Polysphondylium pallidum cells. The majority of activity was present in purified
      plasma membranes. Activity, measured as glucose incorporation from UDPG into NaOH
      insoluble glucan, increased 30-40 fold in the membranes. Increases in activity
      within the cells preceded plasma membrane increases and the enzyme appeared to be
      rapidly transported to the plasma membrane. Intracellular activity was relatively
      low. When cells were incubated with UDPG and when phloretin was included to
      inhibit glucose uptake, no NaOH-insoluble glucan was synthesized. Hence, the UDPG
      binding site was not exposed at the cell-surface. When the NaOH-insoluble glucan
      was digested with endo-beta-1,4-glucanase the products were cellobiose and
      glucose. The glucan could also be precipitated from Schweizer's reagent with
      acetic acid. These results suggest that the glucan contained predominantly beta
      1,4-linkages and may be cellulose. Experiments with cycloheximide confirmed that
      protein synthesis was required for encystment. Labeling of cells with [1-(14)C]
      acetate showed that the synthesis of certain plasma membrane proteins was
      developmentally regulated. A number of proteins (e.g., myosin heavy chains and
      actin) were synthesized during the lag phase and their synthesis was subsequently
      reduced or ceased altogether. Immediately prior to the commencement of cyst wall
      formation seven new plasma membrane proteins were synthesized. These proteins
      were not detected intracellularly, indicating rapid transfer to the plasma
      membrane. The possible relationship between the seven developmentally regulated
      proteins and a postulated "multi-enzyme-complex" involved in cellulose synthesis
      is discussed. Their synthesis may be related to the increase in particles in the
      outer leaflet of the plasma membrane observed during encystment with freeze
      etching (G.W. Erdos and H.R. Hohl, 1980, Cytobios, 29, 7-16). 

PMID- 24302321
TI  - The control of food mobilisation in seeds of Cucumis sativus L. : V. The effect
      of light on lipid degradation.
AB  - The degradation of neutral lipid and the development of lipase activity in
      cucumber cotyledons is stimulated by white light. Malate synthase and isocitrate
      lyase activities show no stimulation. Lipase activity and neutral lipid breakdown
      are also enhanced by red light, far-red light proving ineffective. Far-red light
      reverses the effect of red light indicating the involvement of phytochrome in the
      control of lipase activity. Although light stimulates neutral lipid degradation
      it appears that much of the additional lipid lost is used in the synthesis of
      polar lipid constituents. Furthermore, the influence of light on lipid
      degradation appears to be species dependent. 

PMID- 24302322
TI  - Extent of intracellular pH changes during H(+) extrusion by maize root-tip cells.
AB  - (31)P-Nuclear-magnetic-resonance spectra of maize (Zea mays L.) root tips, that
      had been induced to extrude large amounts of H(+) in response to fusicoccin (FC)
      in the presence of potassium salts, indicate that the cytoplasmic pH does not
      become higher than that of controls. In fact, the cytoplasmic pH may become
      slightly (approx. 0.1 pH unit) lower in cells extruding H(+). Estimations of the
      buffer capacity of the cells show that without active intracellular pH
      regulation, H(+) extrusion caused by FC would cause the intracellular pH to rise
      by at least 0.6 pH unit h(-1). Our results indicate that intracellular pH is
      tightly regulated even during extreme rates of acid extrusion, and that a rise in
      cytoplasmic pH is not the signal linking H(+) extrusion with enhanced organic
      acid synthesis or other intracellular responses to H(+) pumping. 

PMID- 24302323
TI  - Extremely high activities of phosphoenolpyruvate carboxylase in thermogenic
      tissues of Araceae.
AB  - Phosphoenolpyruvate carboxylase activity in extracts of a wide range of
      thermogenic tissues of the Araceae was shown to be in the range 10-100 MUmol g(
      1) fresh weight min(-1) (0.5-3.7 MUmol mg(-1) protein min(-1)). Such high
      activities were not found in non-thermogenic tissues of the Araceae or in
      thermogenic tissues of Aristolochia brasiliensis Mart. and Zucc., Victoria
      amazonica Schomb. and Encephalartos barteri Carruth. During development and
      thermogenesis in the club of Arum maculatum L. the high activities of the
      carboxylase did not lead to any marked accumulation of citrate, isocitrate, 2
      oxoglutarate, fumarate, malate and oxaloacetate. Clubs of Arum maculatum and of
      Arum italicum Miller readily fixed (14)CO2 in the dark, mostly into aspartate,
      malate, alanine and glutamate. Pulse and chase experiments showed that most of
      the fixed carbon was very rapidly metabolized to CO2. The detailed distribution
      suggest that this occurred largely by decarboxylation of C-4 acids. It is
      suggested that thermogenic tissues of the Araceae are characterized by very high
      activities of phosphoenolpyruvate carboxylase, and that in vivo this leads to
      synthesis of C-4 acids which are promptly decarboxylated. 

PMID- 24302324
TI  - Crassulacean acid metabolism (CAM) in Kalanchoe: Changes in intercellular CO2
      concentration during a normal CAM cycle and during cycles in continuous light or
      darkness.
AB  - In the crassulacean acid metabolism (CAM) plant Kalanchoe daigremontiana, the
      internal CO2 concentrations were measured throughout CAM cycles by gas
      chromatography. Under normal dark-light cycles, the internal CO2 concentration
      was near that of the ambient air and increased up to 0.5% during the phase of
      maximum malate decarboxylation. A sharp increase in internal CO2 concentration
      occurring after the first 12 h of the cycle was exhibited by the plants both when
      there was a normal day-night cycle and when the night was replaced by
      illumination, and also when the light period was replaced by darkness. Thus, the
      increase in internal CO2 in the morning does not appear to be primarily
      determined by a light-on signal or by alterations of temperature rather than by
      inherent factors of the leaves. This view is supported further by a steep
      increase in (14)CO2 production from labeted malate occurring during extended
      darkness at a time when the light period would normally begin. The results are
      discussed in particular in relation to of how CAM can control stomata movement. 

PMID- 24302325
TI  - Challenges of nursing handover: a qualitative study.
AB  - The aim of this study was to explore the challenges of nursing handover process
      during shift rotation in hospitals. The research had a descriptive exploratory
      design with a qualitative content analysis approach. To conduct the study, three
      pediatric wards were selected at first. Data were gathered through a 4-month
      observation of nursing handovers by recording the oral conversations of nurses
      during the process and semistructured interviews. Then, qualitative content
      analysis was used for data analysis. Two major themes and five subthemes emerged
      through the data analysis. The first and the second themes were a nonholistic
      approach and poor management, respectively. In general, applying a holistic
      approach and managing handover situations are recommended for nursing managers to
      overcome handover challenges. Future focus could be on addressing handover
      challenges through an action research study. 

PMID- 24302326
TI  - What was hot at the ICS meeting 2013?

PMID- 24302327
TI  - Sex pheromones of rice moth,Corcyra cephalonica Stainton : I. Identification of
      male pheromone.
AB  - Behavioral observations of the rice moth (Corcyra cephalonica, Pyralidae,
      Galleriinae) in the laboratory have shown that a male wing-gland pheromone
      induces attraction of female moths. This pheromone was identified as a blend of
      (E,E) and (Z,E)-farnesal. Wing-gland extracts or synthetic compounds were shown
      to be attractive to females by inducing walking. 

PMID- 24302328
TI  - Sex pheromones of rice moth,Corcyra cephalonica Stainton : II. Identification and
      role of female pheromone.
AB  - Laboratory investigations of mating behavior in the rice moth,Corcyra cephalonica
      Stainton (Lepidoptera: Pyralidae; Galleriinae) showed that male moths are
      attracted at short range to live, virgin female moths and to female abdominal-tip
      extract. Volatiles collected from virgin female moths contained one component
      eliciting an electroantennographic (EAG) response from the male moth, and the
      chemical, spectroscopic, and Chromatographic data on this component were
      consistent with that of synthetic 6,10,14-tri-methyl-2-pentadecanol. This
      compound caused an EAG response from the male moth and attracted male moths in
      the bioassay. The pheromone is thought to play a role in courtship, and the
      synthetic material was shown to cause the male moths to search for a mate and
      attempt copulation. 

PMID- 24302329
TI  - Gallery initiation byTomicus piniperda (Coleoptera: Scolytidae) on scots pine
      trees baited with host volatiles.
AB  - In a trapping experiment, wood chips from freshly cut Scots pine trees attracted
      flying adults of the bark beetleTomicus piniperda (L.) Healthy Scots pine trees,
      which usually are not attacked byT. piniperda, were baited with chips from
      freshly cut trees. In other experiments trees were baited with a mixture of (-)
      alpha-pinene, (+)-3-carene, and terpinolene; the individual monoterpenes; or with
      ethanol alone. All baited treatments were attacked byT. piniperda. Most of the
      attacks resulted in short egg galleries and in larval galleries which were only a
      few millimeters in length. In trees from which a new generation of beetles
      emerged, net reproduction was well below 1.0. Unbaited control trees remained
      unattacked or received a few isolated attacks. 

PMID- 24302330
TI  - Identification of female-produced sex pheromone from banded cucumber
      beetle,Diabrotica balteata leconte (Coleoptera: Chrysomelidae).
AB  - A sex pheromone produced by female banded cucumber beetle adults,Diabrotica
      balteata LeConte, was isolated from volatiles trapped on Porapak Q and identified
      as 6,12-dimethylpentadecan-2-one. The structure was elucidated by spectroscopic
      analyses and confirmed by synthesis. The synthesized racemic compound was equal
      to the purified natural pheromone in eliciting responses by banded cucumber
      beetle males to field traps. A doseresponse characteristic was demonstrated for
      the racemic material formulated on filter paper or rubber septa and placed in
      field traps. The absolute configuration at the C-6 and C-12 positions was not
      established. 

PMID- 24302331
TI  - Theoretical range over which bacteria and nematodes locate plant roots using
      carbon dioxide.
AB  - A theory used to estimate the smallest relative chemical gradient that is
      potentially detectable is given approximately byG>(DCR nu (2)t(3))(-1/2) whereD
      is the diffusion constant andC the concentration of the stimulus chemical,R is
      the effective radius of the receptor,nu the velocity of the organism, andt the
      time period within which the organism measures the concentration. Of these
      factors, time has the strongest influence. Combining this result with available
      information on gradients of carbon dioxide around roots and behavior of bacteria
      and nematodes leads to several conclusions. Bacteria can potentially detect
      carbon dioxide gradients in the layer of water in contact with the root but not
      further away. In contrast, plant-parasitic nematodes can potentially detect
      gradients one meter from a single long root fiber and over 2 m from a plant root
      mass using klinokinesis. A direct approach using klinotaxis can start a few
      centimeters from a single root fiber and half a meter from a root mass. These
      differences are due to differences in the time available to measure the
      concentrations. Increasing the length of a bacterium could increase its ability
      to detect gradients by reducing its rotational diffusion. Collimating stimuli
      that serve to maintain a straight path may provide a means of improving
      chemotaxis by permitting concentration to be measured for longer times during
      klinokinesis. More accurate predictions can be made when more precise data are
      available. The analysis is applicable to a wide variety of other organisms and
      stimuli. 

PMID- 24302332
TI  - Intraspecific pheromone discrimination and substrate marking by atlantic salmon
      parr.
AB  - Attraction and preference behavior patterns shown by Atlantic salmon (Salmo salar
      L.) parr towards intraspecific odors were measured. Salmon parr were attracted to
      tank water in which relatives of their own strain were held but were also
      attracted to tank water containing another strain of their species. When given a
      choice between the two types of tank water, water containing their own strain
      odor was significantly favored over water containing conspecific but nonfamiliar
      odor, revealing that pheromones are present at intraspecific levels in salmonid
      juveniles. Competitive experiments with various extracts suggest that the active
      compounds are most likely produced in the liver and are voided via the intestinal
      tract, as determined by presence of attractants in intestinal contents and bile.
      Intraspecific discrimination was not detected with extracts from either skin
      surface mucus or blood plasma. Extracts from gravel that had been kept below the
      fish in their rearing tanks, however, induced a strain-related preference
      behavior. This suggests an ability for substrate marking by salmonid fishes,
      presumably mediated by deposition of fecal material. Strain discrimination and
      substrate marking are discussed in relation to stationary behavior and homing of
      fishes within discrete populations in natural systems. 

PMID- 24302333
TI  - Diet manipulation affects social behavior of catfish : Importance of body odor.
AB  - Diet manipulation, an habituation test, and chemical analysis of urinary free
      amino acids were used to demonstrate that bullhead catfish (Ictalurus nebulosus)
      naturally detect the body odors of conspecifics and respond to them in a
      predictable fashion. These signals are used in dominance and territorial
      relationships and lead to increased aggression toward chemical "strangers." The
      results support the general notion that nonspecific metabolites, as well as
      specific pheromones, are important in chemical mediation of social behavior. 

PMID- 24302334
TI  - Plant-derived synergists of alarm pheromone from turnip aphid,Lipaphis
      (Hyadaphis) erysimi (Homoptera, Aphididae).
AB  - The turnip aphid,Lipaphis (Hyadaphis) erysimi, responds weakly to (E)-beta
      farnesene, the main component of the alarm pheromone, but the response is
      substantially increased by incorporating plant-derived isothiocyanates,
      identified in aphid volatiles by coupled gas chromatography-single-cell
      recording. 

PMID- 24302335
TI  - Towards chemical characterization of waterborne pheromone of amphipod
      crustaceanMicrodeutopus gryllotalpa.
AB  - Previous studies demonstrated the existence of a waterborne pheromone secreted by
      receptive females of the amphipod crustaceanMicrodeutopus gryllotalpa which
      attracts males. The data were obtained by using a bioassay apparatus based on a
      two-choice test paradigm. The present study reports the results of additional
      tests employing this apparatus which have shed some light on the chemical nature
      of the pheromone. The bioactive substance was isolated from receptive female
      waters with anion exchange resin columns, but not with C-18 reverse-phase
      columns. This suggests that the substance is polar. Another finding of the
      present study was that effluents from the green algaUlva lactuca inhibit males'
      responses to the pheromone. 

PMID- 24302336
TI  - Isolation of 24-methylenecholesterol-derived oxidation products from queen
      honeybee ovaries (Apis mellifica L.).
AB  - The bioecological situation of 24-methylenecholesterol, the main sterol of many
      pollens and previously isolated from larvae, workers, and queens of the
      honeybeeApis mellifica L., is reviewed. A search for steroids in queen honeybee
      ovaries has led to the isolation of three compounds occurring in minute amounts:
      24-methylenecholest-4-en-3-one (1), 24-oxochoiesterol (2), and 24-oxocholest-4-en
      3-one (3), which were identified by direct comparison with authentic samples
      prepared from 24-methyienechoiesterol. These three substances have not been
      detected in lipids from other parts of queen or from worker honeybees, and their
      presence may reflect a particular oxidizing capability of the ovaries. The
      results so far observed are discussed in relationship with previous observations
      reported on honeybees. 

PMID- 24302337
TI  - Identification of triterpenoid feeding deterrent of red pumpkin beetles
      (Aulacophora foveicollis) fromMomordica charantia.
AB  - The triterpenoids isolated from the leaves ofMomordica charantia Linn (bitter
      gourd) were found to elicit feeding-deterrent activity against red pumpkin
      beetles (Aulacophora foveicollis Lucas). The most abundant triterpenoid which
      deterred feeding was identified as momordicine II, 23-O-beta-glucopyranoside of
      3,7,23-trihydroxycucurbita-5,24-dien-19-al. A concentration of 3200MUg/ml and
      above of the triterpenoids caused significant reduction of feeding by red pumpkin
      beetles in in vitro bioassay experiments, which compared favorably with the
      levels of triterpenoids inM. charantia leaves found in nature. 

PMID- 24302338
TI  - Female sex pheromone of the common furniture beetleAnobium punctatum (Coleoptera:
      Anobiidae): Extraction, identification, and bioassays.
AB  - Observations and reports on the common furniture beetleAnobium punctatum
      suggested that, on emergence, females use a sex pheromone to attract males. GLC
      analysis of ovipositor extracts showed the presence of a single component, which
      was found to be active by EAG and coupled GLC-EAG techniques, and to attract
      males in both walking and flying assays. The pheromone was identified by GC-MS as
      2,3-dihydro-2,3,5-trimethyl-6-(1-methyl-2-oxobutyl)-4H-pyran-4-one (stegobinone),
      which is the sex pheromone of another anobiid, the drugstore beetle,Stegobium
      paniceum. MaleA. punctatum responded equally to ovipositor extracts of either
      species, at both the sensory (EAG) and behavioral levels, which poses the
      question as to how species specificity in mate attraction is achieved. 

PMID- 24302339
TI  - Defensive chemistry of the flour beetleTribolium brevicornis (LeC): : Presence of
      known and potential prostaglandin synthetase inhibitors.
AB  - The defensive secretion ofTribolium brevicornis contains 12 organic components,
      including quinones, hydroquinones, hydrocarbons, aromatic ketones, and aromatic
      esters. The two ketones, 2'-hydroxy-4'-methoxyacetophenone and 2'-hydroxy-4'
      methoxypropiophenone, and the two esters, methyl 2,5-dihydroxy-6-methylbenzoate
      and methyl 2,5-dihydroxy-6-ethylbenzoate, represent ca. 0.25% of the biomass of
      the beetles. Mass spectral and NMR analyses were used to elucidate the structures
      of all components. The ketones are potent prostaglandin synthetase inhibitors
      (PSI), and the esters are suspected to be PSI. 

PMID- 24302340
TI  - Extreme sensitivity of grandisal to acids.
AB  - Attempted purification of synthetic racemic grandisal1 by silica gel
      chromatography resulted in severe decomposition. The nature of this reaction was
      studied on silica gel and in an ether solution ofp-toluenesulfonic acid. The same
      products resulted from both reaction systems, although in different ratios. Five
      racemic, rearrangement products were isolated by preparative GC and identified as
      follows: (1RS, 3SR, 6RS)-1-methyl-5-methylenebicyclo[4.2.0]octan-3-ol (4); (1RS,
      3RS, 6RS)-1-methyl-5-methylenebicyclo[4.2.0]octan-3-ol (5); (1RS,3RS,6RS)-1,5
      dimethylbicyclo[4.2.0]oct-4-en-3-ol (6); (1RS,3SR,6RS)-1,5
      dimethylbicyclo[4.2.0]oct-4-en-3-ol(7); and 3-methyl-7-methylenecyclooct-3-en-l
      ol (8). The stereochemical assignments are based on our proposed mechanism, which
      also accounts for all products observed. The racemic bicyclic enone (3) was a by
      product of grandisol (2) oxidation. 

PMID- 24302341
TI  - Allelopathic effect of parthenium (Parthenium hysterophorus L.) extract and
      residue on some agronomic crops and weeds.
AB  - Allelopathic effects of entire shoot extract, plant part extracts, and shoot
      residue of parthenium (Parthenium hysterophorus L.) on corn (Zea mays L.),
      ryegrass (Lolium multiflorum Lam.), wheat (Triticum aestivum L.), velvetleaf
      (Abutilon theophrasti Medik.), and soybean [Glycine max (L) Merr.] growth were
      examined. Parthenium shoot contained water-soluble materials that were toxic to
      root growth of velvetleaf and wheat. At 4% (w/ v) concentration, root growth of
      velvetleaf and wheat were reduced by 60 and 75%, respectively. The order of
      increasing sensitivity to parthenium was ryegrass, corn, wheat, and velvetleaf.
      There was a strong correlation between extract concentration and increased
      toxicity to test species. The toxicity of plant part extracts was also
      concentration dependent. At 1 and 2% (w/v), the inflorescence and leaves caused
      more root inhibition than stem extract. Parthenium shoot incorporated in soil at
      1% (w/w) caused significantly more root inhibition of wheat than soybean, corn,
      and ryegrass. At 4% (w/w), root growth of all the test species was inhibited
      compared to the control. Toxicity of parthenium residue to wheat diminished with
      increasing periods of decomposition. Residue decomposed for four weeks was less
      toxic than the undecomposed residue. 

PMID- 24302342
TI  - Flight and copulation of female spruce budworm in pheromone-permeated air.
AB  - High concentrations of synthetic sex pheromone caused increased flight activity
      among mated female spruce budworm of all ages, a fact that may indicate an
      increase in dispersal. Flight activity also increased among older virgin females,
      but not among females one day old, the age at which they usually mate.
      Receptivity of young virgin females to courting males was not affected by
      pheromone-permeated air. Synthetic sex pheromone is therefore not likely to
      influence mating frequency through its effects on female activity. 

PMID- 24302343
TI  - Differential inhibition by castanospermine of various insect disaccharidases.
AB  - The indolizidine alkaloid, castanospermine (1,6,7,8-tetrahydroxy
      octahydroindolizidine-a stereochemical mimic of glucose found in the Australian
      legumeCastanospermum australe), differentially inhibited cellobiose, lactose,
      maltose, sucrose, and trehalose hydrolyzing enzymes from a broad taxonomic
      spectrum of insects (19 species from 12 different families). It was a potent
      inhibitor of cellobiase activity of all insects tested (50% inhibition at <3.2 *
      10(-5) M castanospermine). With one exception, it also inhibited lactase activity
      of all insects examined. Only in the sap-feeding Homoptera did castanospermine
      inhibit all disaccharidase activities assayed. Trehalase activity of the
      Lepidoptera and Diptera was generally inhibited by castanospermine, whereas
      inhibition of trehalase activity of the Coleoptera by castanospermine was
      exiguous or not detectable. Castanospermine was a significant feeding deterrent
      towards pea aphids,Acyrthosiphon pisum, with an ED50 of 1 * 10(-4) M in
      artificial diets. Two compounds stereochemically related to castanospermine,
      deoxynojirimycin and 6-epicastanospermine, were each slightly active at deterring
      the feeding of green peach aphids,Myzus persicae, (ED50=2.5 * 10(-3) M) and
      greenbugs,Schizaphis graminum (ED50=5 * 10(-3) M), respectively. Among the
      insects studied there was no distinct relationship between enzyme inhibition and
      adaptation to host plants containing castanospermine or other toxic alkaloids. 

PMID- 24302344
TI  - Chemical stimulants and deterrents regulating acceptance or rejection of
      crucifers by cabbage butterflies.
AB  - GravidPieris rapae butterflies oviposit on many, but not all, crucifers.
      Rejection ofErysimum cheiranthoides andCapsella bursa-pastoris was initially
      explained by the presence of chemical deterrents in the plants. Analyses and
      bioassays of plant extracts indicated the absence of oviposition stimulants inC.
      bursa-pastoris, but similar chemical separation ofE. cheiranthoides extracts
      revealed the presence of stimulants as well as deterrents. Choice tests
      illustrate how acceptance or rejection of a plant by an insect may depend on the
      balance of positive and negative chemical stimuli within the plant. 

PMID- 24302345
TI  - (Z)-11-octadecenyl acetate, an aggregation pheromone inDrosophila simulans.
AB  - Existence of a male-produced pheromone, which attracts both males and females in
      a wind-tunnel olfactometer, has been demonstrated inDrosophila simulans
      (Sturtevant). A pheromone component was identified as (Z)-11-octadecenyl acetate
      (Z11-18: Ac), also known ascis-vaccenyl acetate. The pheromone is synergized by
      food volatiles. In bioassay ca. 1/1000 of a mature male equivalent of Z11-18: Ac
      is attractive and activity increases with increased amounts of Z11-18: Ac. Flies
      do not begin responding to Z11-18: Ac until after they have been away from food
      for at least 2 hr. Z11-18: Ac is transferred from the male to the female during
      mating, and the female emits the majority of the transferred Z11-18: Ac within 6
      hr after mating. 

PMID- 24302346
TI  - Synthesis and characterisation of chelated cationic ReI(CO)3bis(NHC)(WCA)
      complexes.
AB  - Twelve novel Re(I) acetonitrile complexes of the type [Re(CO)3(L)(MeCN)][WCA],
      with L being a chelating bis(NHC) ligand with alkylene-bridged and N-substituted
      bis(imidazolineylidene) moieties, and WCA (WCA = weakly coordinating anion)
      representing PF6(-) and [Al(OC(CF3)3)4](-), have been synthesized. 1D and 2D NMR
      spectroscopy as well as IR spectroscopy, elemental analysis and X-ray
      crystallography have been applied in characterization. The propylene-bridged
      complex, displaying mesitylene groups R, is discussed in depth revealing
      interesting chemical behaviour both in solid state and in solution. DFT
      calculations were undertaken to better understand the properties of such
      compounds. In addition, the X-ray molecular structure of the first rhenium CCC
      pincer complex is reported.

PMID- 24302347
TI  - Orienting semi-conducting pi-conjugated polymers.
AB  - The present review focuses on the recent progress made in thin film orientation
      of semi-conducting polymers with particular emphasis on methods using epitaxy and
      shear forces. The main results reported in this review deal with regioregular
      poly(3-alkylthiophene)s and poly(dialkylfluorenes). Correlations existing between
      processing conditions, macromolecular parameters and the resulting structures
      formed in thin films are underlined. It is shown that epitaxial orientation of
      semi-conducting polymers can generate a large palette of semi-crystalline and
      nanostructured morphologies by a subtle choice of the orienting substrates and
      growth conditions. 

PMID- 24302348
TI  - Crystal structure of Plasmodium vivax FK506-binding protein 25 reveals
      conformational changes responsible for its noncanonical activity.
AB  - The malarial parasites currently remain one of the most dreadful parasites, which
      show increasing trend of drug resistance to the currently available antimalarial
      drugs. Thus, the need to identify and characterize new protein targets in these
      parasites can aid to design novel therapeutic strategies to combat malaria.
      Recently, the conserved FK506-binding protein family members with molecular
      weight of 35 kDa from Plasmodium falciparum and Plasmodium vivax (referred to as
      PfFKBP35 and PvFKBP35, respectively) were identified for drug targeting. Further
      data mining revealed a 25-kDa FKBP (FKBP25) family member present in the
      parasites. FKBP25 belongs to a unique class of FKBP, because it is a nuclear FKBP
      with multiple protein-binding partners. Apart from immune regulation, it is also
      known for its chaperoning role in various cellular processes such as
      transcription regulation and trafficking. Here, we present the biochemical
      characterization and 1.9-A crystal structure of an N-terminal truncated FKBP25
      from P. vivax (PvFKBP25(72-209)). The protein reveals the noncanonical nature
      with unique structural changes observed in the loops flanking the active site,
      concealing the binding pocket. Further, a potential calmodulin-binding domain,
      which is absent in human FKBP25, is observed in this protein. Although the
      functional implication of Plasmodium FKBP25 in malaria still remains elusive, we
      speculate that the notable conformational changes in its structure might serve as
      an overture in understanding its molecular mechanism.

PMID- 24302349
TI  - Where it all starts.

PMID- 24302350
TI  - Egocentricity, coenocentrism, and the nature of human fulfillment.
AB  - This essay explores the reasons why human beings suffer unnecessarily and
      suggests the means by which that suffering may be alleviated. Normal
      psychological functioning isegocentric, a mode of being that derives from a
      profound sense of deficiency and proceeds with a quest to prove being and worth
      in face of the world.Coenocentrism is an awareness of inner commonality and
      relatedness that relieves a person's feelings of isolation, separateness, and
      difference from others. Coenocentrism requires a transformation of the self
      through ecstatic experience and a relinquishing of one's own basic tendencies and
      understandings of the self and world. 

PMID- 24302351
TI  - Recovering masculine spirituality: A Jungian reflection.
AB  - A Jungian-oriented reflection is presented on the theoretical description of and
      possible clinical response to male midlife transitions within pastoral
      psychotherapy. After a brief introduction, a focused case vignette is offered,
      followed by a detailed theoretical discussion and outline of significant psycho
      spiritual frames in the treatment of such clients and this crucial initiatory
      threshold in the male's life experience. 

PMID- 24302352
TI  - Therapeutic transformation in ritual, therapy, and human development.
AB  - A multidisciplinary review and synthesis of transcultural and psychodynamic
      research reveal a common underlying process of therapeutic transformation in
      healing ritual, psychosocial therapy, and human development. A conceptual model
      of this process is presented which provides a transcultural and interreligious
      guide for planning therapy, for establishing mutual understanding between
      religious and secular professional helpers, and for recognizing human growth
      potential in developmental crises. 

PMID- 24302353
TI  - Religious and therapeutic elements in Sufi teaching stories.
AB  - Like the teaching stories of many other religions-the parables of Jesus, Zen
      koans, Hasidic tales-the stories of the Sufis, or Islamic mystics, offer
      important insights into the nature of religious experience and emotional well
      being. This paper discusses the comments of selected Sufi tales on the basic
      structure of situations, non-rational or lateral problem-solving techniques, the
      process of consciousness-raising, and the experience of confronting unexpected
      reality. 

PMID- 24302354
TI  - Religious women and the problem of anger.
AB  - The experience of anger and its expression are sources of difficulty in the lives
      of many religious women. This article examines the circumstances that engender
      anger at the interpersonal and institutional levels. Elements that have assisted
      religious in coming to a mature integration of anger at the interpersonal
      religious community levels are noted; the advantages and limitations of support
      groups are examined; and several techniques for coping with anger are indicated.
      The ability to transcend anger through the achievement of forgiveness is
      explored. 

PMID- 24302355
TI  - Metaphysics and the vision of health.
AB  - Whitehead's philosophy of organism provides the most comprehensive and adequate
      basis for the transformation of contemporary health care. In contrast to the
      reductionist and fragmentary medical models supported by Cartesian dualism,
      materialism, and idealism, Whitehead's metaphysics serves as the foundation for a
      holistic health care system, inclusive of the dimensions of spirituality,
      emotions, physical existence, and environment as they relate to health and
      illness. Whitehead's understanding of the relationship of mind and body and the
      role of the divine in the creative process encourages the inclusion of pastoral
      care, imaging, and meditation in responding to illness. 

PMID- 24302357
TI  - 25th anniversary article: Design of polymethine dyes for all-optical switching
      applications: guidance from theoretical and computational studies.
AB  - All-optical switching--controlling light with light--has the potential to meet
      the ever-increasing demand for data transmission bandwidth. The development of
      organic pi-conjugated molecular materials with the requisite properties for all
      optical switching applications has long proven to be a significant challenge.
      However, recent advances demonstrate that polymethine dyes have the potential to
      meet the necessary requirements. In this review, we explore the theoretical
      underpinnings that guide the design of pi-conjugated materials for all-optical
      switching applications. We underline, from a computational chemistry standpoint,
      the relationships among chemical structure, electronic structure, and optical
      properties that make polymethines such promising materials.

PMID- 24302356
TI  - Use of quantitative mass spectrometric analysis to elucidate the mechanisms of
      phospho-priming and auto-activation of the checkpoint kinase Rad53 in vivo.
AB  - The cell cycle checkpoint kinases play central roles in the genome maintenance of
      eukaryotes. Activation of the yeast checkpoint kinase Rad53 involves Rad9 or Mrc1
      adaptor-mediated phospho-priming by Mec1 kinase, followed by auto-activating
      phosphorylation within its activation loop. However, the mechanisms by which
      these adaptors regulate priming phosphorylation of specific sites and how this
      then leads to Rad53 activation remain poorly understood. Here we used
      quantitative mass spectrometry to delineate the stepwise phosphorylation events
      in the activation of endogenous Rad53 in response to S phase alkylation DNA
      damage, and we show that the two Rad9 and Mrc1 adaptors, the four N-terminal Mec1
      target TQ sites of Rad53 (Rad53-SCD1), and Rad53-FHA2 coordinate intimately for
      optimal priming phosphorylation to support substantial Rad53 auto-activation.
      Rad9 or Mrc1 alone can mediate surprisingly similar Mec1 target site
      phosphorylation patterns of Rad53, including previously undetected tri- and
      tetraphosphorylation of Rad53-SCD1. Reducing the number of TQ motifs turns the
      SCD1 into a proportionally poorer Mec1 target, which then requires the presence
      of both Mrc1 and Rad9 for sufficient priming and auto-activation. The
      phosphothreonine-interacting Rad53-FHA domains, particularly FHA2, regulate
      phospho-priming by interacting with the checkpoint mediators but do not seem to
      play a major role in the phospho-SCD1-dependent auto-activation step. Finally,
      mutation of all four SCD1 TQ motifs greatly reduces Rad53 activation but does not
      eliminate it, and residual Rad53 activity in this mutant is dependent on Rad9 but
      not Mrc1. Altogether, our results provide a paradigm for how phosphorylation site
      clusters and checkpoint mediators can be involved in the regulation of signaling
      relay in protein kinase cascades in vivo and elucidate an SCD1-independent Rad53
      auto-activation mechanism through the Rad9 pathway. The work also demonstrates
      the power of mass spectrometry for in-depth analyses of molecular mechanisms in
      cellular signaling in vivo. 

PMID- 24302358
TI  - Somatic hybridization of sexually incompatible petunias: Petunia parodii, Petunia
      parviflora.
AB  - Somatic hybrid plants were regenerated following the fusion of leaf mesophyll
      protoplasts of P. parodii with those isolated from a nuclear-albino mutant of P.
      parviflora. Attempts at sexual hybridization of these two species repeatedly
      failed thus confirming their previously established cross-incompatibility.
      Selection of somatic hybrid plants was possible since protoplasts of P. parodii
      would not develop beyond the cell colony stage, whilst those of the somatic
      hybrid and albino P. parviflora produced calluses. Green somatic hybrid calluses
      were visible against a background of albino cells/calluses, and upon transfer to
      regeneration media gave rise to shoots. Shoots and the resultant flowering plants
      were confirmed as somatic hybrids based on their growth habit, floral
      pigmentation and morphology, leaf hair structure, chromosome number and Fraction
      1 protein profiles. The relevance of such hybrid material for the development of
      new, and extensively modified cultivars, is discussed. 

PMID- 24302359
TI  - The significance of genic balance to endosperm development in interspecific
      crosses.
AB  - The endosperm has played a significant role in the evolution of angiosperms
      because of its physiological and genetic relationships to the embryo. One
      manifestation of this evolutionary role is its abnormal development in
      interploidy crosses. It is now established that the endosperm develops abnormally
      in interploidy-intraspecific crosses when the maternal: paternal genome ratio
      deviates from 2?1 in the endosperm itself. We propose an Endosperm Balance Number
      (EBN) hypothesis to explain endosperm development in both interploidy
      intraspecific and interspecific crosses. Each species is assigned an EBN on the
      basis of its crossing behavior to a standard species. It is the EBN which
      determines the effective ploidy in the endosperm of each species, and it is the
      EBNs which must be in a 2?1, maternal:paternal ratio. The EBN of a species may be
      determined by a few genes rather than the whole genome. This hypothesis brings
      most intraspecific-interploidy and interspecific crossing data under a single
      concept with respect to endosperm function. The implications of this hypothesis
      to isolating mechanisms, 2n gametes, the evolution of disomic polyploids, and
      reciprocal differences in seed development are discussed. 

PMID- 24302360
TI  - Gynodioecy as a possible populational strategy for increasing reproductive
      output.
AB  - Cytoplasmic male steriles occur regularly in wild populations of the annual
      crucifer Hirschfeldia incana Lagr.-Foss. in Israel. In these plants numbers of
      ovules per flower, numbers of seed per fruit, and total seed weights per plant
      are slightly higher than in the hermaphrodites with which they mate. Yet their
      frequencies in wild populations do not exceed 2-10 per cent. There are no signs
      of incipient dioecy. The species is self incompatible and no mechanisms to
      enforce outcrossing are needed. It is argued that in this and similar cases
      gynodioecy functions as a pollen saving measure. Precise pollen presentation in
      the flower renders some of the pollen redundant and facilitates its abolition in
      a sector of the population. It is possible that the enhanced seed fecundity of
      the pollenless sector stems from a greater availability of plant resources for
      seed production in the unisexual than in the bisexual seed parent. 

PMID- 24302361
TI  - The effect of positive assortative mating at one locus on a second linked locus :
      Part 2: Limiting characteristics of gametic and genotypic structures.
AB  - Considerations proceed from a model of positive assortative mating based on
      genotype at one locus, with an arbitrary number of alleles, assuming no
      selection, mutation, or migration, hypothetically infinite population size, and
      discrete non-overlapping generations. From these conditions, inferences are made
      about the genotypic structure at a linked locus, as well as about the
      corresponding 2-locus gametic structure.The following main results are presented:
      in the course of the generations, the genotypic structure at the second locus and
      the 2-locus gametic structure always tend to a limit responsive to the initial
      conditions concerning the joint genotypic structure at the two loci and the
      degree of assortativity and linkage. A complete, analytical representation of the
      limits is given. In particular, if assortative mating is only partial and at the
      same time linkage is not complete, a population is not able to maintain a
      permanent deviation of the gametic structure from linkage equilibrium, and thus
      the genotypic structure at the second locus tends to Hardy-Weinberg proportions.
      On the other hand, if initial linkage disequilibrium is combined with partial
      assortative mating and complete linkage (or with complete assortative mating and
      unlinked loci) the population maintains this disequilibrium and thus the
      genotypic structure at the second locus need not tend to Hardy-Weinberg
      proportions. It turns out that the conditions not only of complete linkage, but
      also of unlinked loci together with complete assortativity, imply no change in
      gametic structure from the initial structure.In order to demonstrate the
      influence of several parameters on the speed of convergence to and the magnitude
      of the respective limits, several graphs are included. 

PMID- 24302362
TI  - Long-term selection for a quantitative character in large replicate populations
      of Drosophila melanogaster : Part 3: The nature of residual genetic variability.
AB  - Six replicate lines of Drosophila melanogaster, which had been selected for
      increased abdominal bristle number for more than 85 generations, were assayed by
      hierarchical analysis of variance and offspring on parent regression immediately
      after selection ceased, and by single-generation realised heritability after more
      than 25 generations of subsequent relaxed selection.Half-sib estimates of
      heritability in 5 lines were as high as in the base population and much higher
      than observed genetic gains would suggest, excluding lack of sufficient additive
      genetic variance as a cause of ineffective selection in these lines. Also, there
      was considerable diversity among the six lines in composition of phenotypic
      variability: in addition to differences in the additive genetic component, one or
      more of the components due to dominance, epistasis, sex-linkage or genotype
      environment interaction appeared to be important in different lines.Even after
      relaxed selection, single-generation realised heritabilities in four lines were
      as high as in the base population. As a large proportion of total genetic gain
      must have been made by fixation of favourable alleles, the compensatory increase
      of genetic variability has been sought in a genetic model involving genes at low
      initial frequencies, enhancement of gene effects during selection and/or new
      mutations. 

PMID- 24302363
TI  - Effect of temperature on membrane fluidity and protoplast fusion.
AB  - The fusion of plant protoplasts is greatly enhanced by a rise in temperature in
      the presence of the fusion-inducing agents polyethylene glycol or polyvinyl
      alcohol. Kinetic analysis of this reaction reveals that membrane fluidity is
      important in regulating the fusion process. 

PMID- 24302364
TI  - Competitive ability of maize pollen. Intergametophytic effects.
AB  - Intergametophytic influences on pollen competitive ability were studied by means
      of the pollen mixture technique: mixtures of pollen from different genetic
      sources, marked for the presence of the normal or the mutant allele of the opaque
      2 gene, were used to pollinate o2o2 female plants. The variation of relative
      frequency of one of the two kernel types from apex to base of the resulting ear,
      made it possible to measure the competitive ability by regression
      coefficients.The effect of the pollen marker on the character was estimated by
      analyzing the progeny of heterozygous o2/+ plants self-pollinated through four
      generations. The o2 allele-bearing pollen revealed a slower germination rate than
      the dominant counterpart; no differences between the two pollen types were
      observed with regard to tube growth rate.The occurrence of intergametophytic
      interactions was confirmed: the competitive ability of a line varied according to
      the genotype of the competing pollen. Thus, this component has to be taken into
      account in considering male gametophyte fertilization ability. 

PMID- 24302365
TI  - Diallel analysis of heading date in rice (Oryza sativa L.).
AB  - The genetics of heading date was investigated in an 8*8 diallel set of crosses
      involving diverse rice cultivars. Wr, Vr graph analysis revealed the presence of
      a complementary type of non-allelic interaction which apparently affected the
      position and slope of the regression line such as if there were overdominance.
      Omission of two interacting parents resulted in a 6*6 subset of diallel crosses
      from which, as observed in the Wr, Vr graph, the non-allelic interaction had
      disappeared and the regression line exhibited partial dominance. Estimates of the
      genetic components of variation were in close conformity with the results
      obtained from the Wr, Vr graph: the average degree of dominance, as measured by
      (H1/D)(1/2), was in overdominance range in the interacting 8*8 set of diallel
      crosses whereas it was reduced to partial dominance in the non-interacting 6*6
      set of crosses. Further analysis by a standardized deviations graph indicated
      that earliness was controlled, on the average, by an excess of dominant alleles. 

PMID- 24302366
TI  - Messenger RNA encoding a glutathione-S-transferase responsible for herbicide
      tolerance in maize is induced in response to safener treatment.
AB  - Glutathione-S-transferases (GST's) in maize represent a family of enzymes which
      conjugate glutathione to several major classes of pre-emergent, selective
      herbicides. Chemicals termed safeners have been demonstrated to increase the
      tolerance of maize toward such herbicides when the maize seed has been previously
      treated with safeners. It has subsequently been shown that corresponding
      increases in glutathione-S-transferase species occur. To determine whether these
      compounds act at a transcriptional level we have used synthetic oligonucleotide
      probes to isolate cDNA clones encoding the major GST polypeptide subunit,
      designated GST A. The identity of the clones has been confirmed by hybrid
      selected mRNA translation and immunoprecipitation using antibodies made against
      this GST species as well as by production of active GST in yeast cells
      transformed with an expression vector containing the cloned DNA. GST A has been
      found to be encoded in a mRNA of 1.1 kb. Sequencing of cDNA products obtained by
      primer extension of maize mRNA using our oligonucleotide probes is consistent
      with this mRNA corresponding to the isolated cDNA clone. Using the clone as a
      probe for Northern analysis we have found a three to four-fold increase in the
      steady state level of this mRNA in maize tissue grown from safener-treated seeds.
      The level of safener which gives this induction is comparable to that required to
      obtain herbicide tolerance in the field. 

PMID- 24302367
TI  - Sequences of initiator and elongator methionine tRNAs in bean mitochondria :
      Localization of the corresponding genes on maize and wheat mitochondrial genomes.
AB  - Two bean mitochondria methionine transfer RNAs, purified by RPC-5 chromatography
      and two-dimensional gel electrophoresis, have been sequenced usingin vitro post
      labeling techniques.One of these tRNAs(Met) has been identified by formylation
      using anE. coli enzyme as the mitochondrial tRNAF (Met). It displays strong
      structural homologies with prokaryotic and chloroplast tRNAF (Met) sequences
      (70.1-83.1%) and with putative initiator tRNAm (Met) genes described for wheat,
      maize andOenothera mitochondrial genomes (88.3-89.6%).The other tRNA(Met), which
      is the mitochondrial elongator tRNAF (Met), shows a high degree of sequence
      homology (93.3-96%& with chloroplast tRNAm (Met), but a weak homology (40.7%)
      with a sequenced maize mitochondrial putative elongator tRNAm (Met) gene.Bean
      mitochondrial tRNAF (Met) and tRNAm (Met) were hybridized to Southern blots of
      the mitochondrial genomes of wheat and maize, whose maps have been recently
      published (15, 22), in order to locate the position of their genes. 

PMID- 24302368
TI  - Transcription of the S-2 maize mitochondrial plasmid.
AB  - Mitochondria from S (male-sterile) and RU (male-fertile) maize cytoplasms contain
      both autonomous plasmids and copies of plasmid sequences integrated into the
      mitochondrial genome. The S-2 plasmid in S, which appears essentially the same as
      the R-2 plasmid in RU, contains two large open reading frames (ORFs) that may
      encode gene products required for plasmid maintainance and replication.
      Transcripts from both ORF1 and ORF2 are readily detected in cytoplasms having
      free plasmids. The 5' ends of these RNAs, which are transcribed from opposite
      ends of the plasmid, correspond to nucleotide position 32 within each of the 208
      bp terminal inverted repeats (IRs). In Normal (fertile) and Revertant S (now
      fertile) cytoplasms that have only integrated copies of the S-2 sequence,
      transcripts from the S-2 ORFs are either present in greatly reduced amounts, or
      not detectable. The loss of transcriptional activity is correlated with deletions
      of, or nucleotide changes within, the IRs associated with the integrated S-2
      ORFs. Evidence for transcription of non-plasmid DNA adjacent to integrated IRs
      suggests that both free-plasmid and integrated forms of the plasmid IR have
      promoter-like activity. 

PMID- 24302369
TI  - Clones from a shooty tobacco crown gall tumor I: deletions, rearrangements and
      amplifications resulting in irregular T-DNA structures and organizations.
AB  - Transformed clones from a shooty tobacco crown gall tumor, induced
      byAgrobacterium tumefaciens strain LBA1501, having a Tn1831 insertion in the
      auxin locus, were investigated for their T-DNA structure and expression. In
      addition to clones with the expected phenotype, i.e. phytohormone autonomy,
      regeneration of non-rooting shoots and octopine synthesis (Aut(+)Reg(+)Ocs(+)
      'type I' clones), clones were obtained with an aberrant phenotype. Among these
      were the Aut(-)Reg(-)Ocs(+) 'type II' clones. Two shooty type I clones and three
      type II callus clones (all randomly chosen) as well as a rooting shoot
      regenerated from a type II clone via a high kinetin treatment, all had a T-DNA
      structure which differed significantly from 'regular' T-DNA structures. No Tn1831
      DNA sequences were detected in these clones. The two type I clones were
      identical: they both contained the same highly truncated T-DNA segments. One TL
      DNA segment of approximately 0.7 kb, originating form the left part of the TL
      region, was present at one copy per diploid tobacco genome. Another segment with
      a maximum size of about 7 kb was derived from the right hand part of the TL
      region and was present at minimally two copies. Three copies of a truncated TR
      DNA segment were detected, probably starting at the right TR-DNA border repeat
      and ending halfway the regular TR-region. Indications have been obtained that at
      least some of the T-DNA segments are closely linked, sometimes via intervening
      plant DNA sequences. The type I clones harbored TL-DNA transcripts 4, 6a/b and 3
      as well as TR-DNA transcript 0'. The type II clones harbored three to six highly
      truncated T-DNA segments, originating from the right part of the TL-region. In
      addition they had TR-DNA segments, similar to those of the type I clones. On
      Northern blots TR-DNA transcripts 0' and 1' were detected as well as the TL-DNA
      transcripts 3 and 6a/b and an 1800 bp hybrid transcript (tr.Y) containing gene 6b
      sequences. Possible origins of the observed irregularities in T-DNA structures
      are discussed in relation to fidelity of transformation of plant cells
      viaAgrobacterium. 

PMID- 24302370
TI  - Clones from a shooty tobacco crown gall tumor II: irregular T-DNA structures and
      organization, T-DNA methylation and conditional expression of opine genes.
AB  - Transformed clones from a shooty tobacco crown gall tumor, induced
      byAgrobacterium tumefaciens strain LBA1501, having the auxin locus of the TL
      region inactivated by a Tn1831 insertion, were investigated for their T-DNA
      structure and expression. It has been described previously (28) that in addition
      to clones with an expected phenotype (phytohormone independent growth in tissue
      culture (Aut(+)), shoot regeneration (Reg(+)) and octopine synthesis (Ocs(+))),
      clones were obtained with an aberrant phenotype. One of these clones, TSO38, is
      Aut(+)Reg(+) but shows little or no octopine synthesis activity (Ocs(-)).
      Subclones of TSO38, however, are either Ocs(-) or Ocs(+). Ocs(-) shoots become
      Ocs(+) under certain states of differentiation, indicating that the octopine
      synthase gene is present. The fact that in the Ocs(-) subclones the octopine
      synthase gene is not expressed, is probably due to DNA methylation (29). The
      present paper describes that shoots derived from both an Ocs(+) and an Ocs(-)
      subclone of TSO38, which were negative for the presence of mannopine (Mas(-)) and
      agropine (Ags(-)), became Mas(+)Ags(+) after culturing on medium containing the
      hypomethylating agent 5-azacytidine. This means that both in the Ocs(-) line and
      in the Ocs(+) line expression of TR-DNA opine genes most likely was hampered by
      DNA methylation. The T-DNA structures of an Ocs(-) and an Ocs(+) TSO38 subclone
      proved to be identical and surprisingly complex. No intact copy of Tn1831 was
      present. TL-DNA and TR-DNA segments, present in high copy numbers, were
      truncated; several T-DNA segments existed in tandem arrangements. When DNA from
      an Ocs(+) and an Ocs(-) subclone of TSO38 were compared for cleavability by the
      methylation sensitive restriction enzymes HpaII and MspII, differences were
      detected, but it became also clear that both lines contained methylated T-DNA
      segments. This indicates that the Ocs(-) and the Ocs(+) TSO38 subclones differ
      only quantitatively in respect to degree of T-DNA methylation. 

PMID- 24302371
TI  - A simple gene-expression system for the small subunit of ribulose bisphosphate
      carboxylase in leaves ofNicotiana sylvestris.
AB  - InNicotiana sylvestris only four transcripts coding for the small subunit of
      RUBISCO are present in leaves. They are very closely related as they are
      identical in the nucleotide sequence of the non-coding regions and show only
      three silent point differences in the region coding for the mature peptide.The
      main difference among these four transcripts lies in the length of the non-coding
      regions. Half of the SmRNA population as confirmed by direct RNA sequencing has
      an additional nucleotide sequence in the leader region. Two cDNAs have an
      additional nucleotide sequence at the end of the 3' non-coding region. Based on
      these criteria the transcripts were classified into two groups:.group I has a 73
      nucleotide-long leader sequence and the nucleotides T, A and C at position 327,
      432 and 519 in the coding region..group II has a 60-nucleotide-long leader
      sequence and the nucleotides C, G and T at these positions in the coding
      region.The two cDNAs showing a difference in the length of the 3' non-coding
      region belong to group II.The study of all these transcripts argues for the
      possibility that only two families of genes are expressed in leaves ofN.
      sylvestris. 

PMID- 24302372
TI  - Unique repetitive sequences of 170 bp inChlorella.
AB  - Cot analysis ofChlorella DNA revealed that the genome of the unicellular green
      alga contained a small amount of repetitive sequences (at most 15% of the total
      DNA). Short repetitive sequences (SRS) of 170 bp produced by enzymatic digestion
      of algal DNA with eitherHaeIII,HinfI, orPstI, were found by polyacrylamide gel
      electrophoresis, and their copy number was estimated to be a few hundred (about
      2% of the total repetitive sequences). All three members showed high sequence
      homology and could be be unified into one family, 'HaeIII family'. The family was
      divided further into two subfamilies,HinfI- (HaeIII-andHinfI-SRS) andPstI-(PstI
      SRS) subfamilies, based on small sequence differences among the members.
      TheHaeIII family had characteristic structural features, including a considerable
      number of small unique sequence units (purine-CC) and both direct and inverted
      repeats, and were organized in tandem arrays in the genome. 

PMID- 24302373
TI  - fMRI and sleep correlates of the age-related impairment in motor memory
      consolidation.
AB  - Behavioral studies indicate that older adults exhibit normal motor sequence
      learning (MSL), but paradoxically, show impaired consolidation of the new memory
      trace. However, the neural and physiological mechanisms underlying this
      impairment are entirely unknown. Here, we sought to identify, through functional
      magnetic resonance imaging during MSL and electroencephalographic (EEG)
      recordings during daytime sleep, the functional correlates and physiological
      characteristics of this age-related motor memory deficit. As predicted, older
      subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral
      changes that reflect consolidation) and had reduced sleep spindles compared with
      young subjects. Brain imaging analyses also revealed that changes in activity
      across the retention interval in the putamen and related brain regions were
      associated with sleep spindles. This change in striatal activity was increased in
      young subjects, but reduced by comparison in older subjects. These findings
      suggest that the deficit in sleep-dependent motor memory consolidation in elderly
      individuals is related to a reduction in sleep spindle oscillations and to an
      associated decrease of activity in the cortico-striatal network.

PMID- 24302374
TI  - Pin site care for preventing infections associated with external bone fixators
      and pins.
AB  - BACKGROUND: Metal pins are used to apply skeletal traction or external fixation
      devices in the management of orthopaedic fractures. These percutaneous pins
      protrude through the skin, and the way in which they are treated after insertion
      may affect the incidence of pin site infection. This review set out to summarise
      the evidence of pin site care on infection rates. OBJECTIVES: To assess the
      effect on infection rates of different methods of cleansing and dressing
      orthopaedic percutaneous pin sites. SEARCH METHODS: In September 2013, for this
      third update, we searched the Cochrane Wounds Group Specialised Register; The
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library);
      Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid
      EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: We evaluated all randomised
      controlled trials (RCTs) that compared the effect on infection and other
      complication rates of different methods of cleansing or dressing orthopaedic
      percutaneous pin sites. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the citations retrieved by the search strategies for
      reports of relevant RCTs, then independently selected trials that satisfied the
      inclusion criteria, extracted data and undertook quality assessment. MAIN
      RESULTS: A total of eleven trials (572 participants) were eligible for inclusion
      in the review but not all participants contributed data to each comparison. Three
      trials compared a cleansing regimen (saline, alcohol, hydrogen peroxide or
      antibacterial soap) with no cleansing (application of a dry dressing), three
      trials compared alternative sterile cleansing solutions (saline, alcohol,
      peroxide, povidone iodine), three trials compared methods of cleansing (one trial
      compared identical pin site care performed daily or weekly and the two others
      compared sterile with non sterile techniques), one trial compared daily pin site
      care with no care and six trials compared different dressings (using different
      solutions/ointments and dry and impregnated gauze or sponges). One small blinded
      study of 38 patients found that the risk of pin site infection was significantly
      reduced with polyhexamethylene biguanide (PHMB) gauze when compared to plain
      gauze (RR 0.23, 95% CI 0.12 to 0.44) (infection rate of 1% in the PHMB group and
      4.5% in the control group) but this study was at high risk of bias as the unit of
      analysis was observations rather than patients. There were no other statistically
      significant differences between groups in any of the other trials. AUTHORS'
      CONCLUSIONS: The available trial evidence was not extensive, was very
      heterogeneous and generally of poor quality, so there was insufficient evidence
      to be able to identify a strategy of pin site care that minimises infection
      rates. Adequately-powered randomised trials are required to examine the effects
      of different pin care regimens, and co-interventions - such as antibiotic use -
      and other extraneous factors must be controlled in the study designs.

PMID- 24302375
TI  - The polysaccharide structure of potato cell walls: Chemical fractionation.
AB  - Cell walls of potato tubers were fractionated by successive extraction with
      various reagents. A slightly degraded pectic fraction with 77% galacturonic acid
      was extracted in hot, oxalate-citrate buffer at pH 4. A further, major pectic
      fraction with 38% galacturonic acid was extracted in cold 0.1 M Na2CO3 with
      little apparent degradation. These two pectic fractions together made up 52% of
      the cell wall. Most of the oxalate-citrate fraction could alternatively be
      extracted with cold acetate-N,N',N'-tetracetic acid (CDTA) buffer, a non
      degradative extractant which nevertheless removed essentially all the calcium
      ions. This fraction was therefore probably held only by calcium binding, and the
      remainder of the pectins by covalent bonds. Electrophoresis showed that both
      pectic fractions contained a range of molecular types differing in composition,
      with a high arabinose: galactose ratio as well as much galacturonic acid in the
      most extractable fractions. From methylation data, the main side-chains were 1,4'
      linked galactans and 1,5'-linked arabinans, with smaller quantities of covalently
      attached xyloglucan. Extraction with NaOH-borate removed a small hemicellulose
      fraction and some cellulose. The main hemicelluloses were apparently a
      galactoxyloglucan, a mannan or glucomannan and an arabinogalactan. 

PMID- 24302376
TI  - A thioredoxin-activated fructose-1,6-bisphosphatase from the cyanobacterium
      Synechococcus 6301.
AB  - Fructose-1,6-bisphosphatase was isolated from the cyanobacterium Synechococcus
      6301 by acid precipitation, ammonium-sulfate fractionation, and Sephadex gel
      chromatography. The purified enzyme needed thiols and MgCl2 for activity. The
      following Km-values were obtained: a) for fructose-1,6-bisphosphate: 1.7 mM; b)
      for MgCl2: 12.5 mM; c) for dithiocrythritol: 0,56 mM; d) for glutathione: 14 mM;
      e) for mercaptoethanol: 22 mM; f) for cysteine: 50 mM. Thioredoxin B isolated
      from this organism will activate this fructose-1,6-bisphosphatase. The Km of
      thioredoxin B for this fructose-1,6-bisphosphatase was determined to be 1.7 MUM,
      endicotiy that thioredoxin might activate the fructose-1,6-bisphosphatase in
      Synechococcus in vivo. 

PMID- 24302377
TI  - Cellulose and 1,3-glucan synthesis during the early stages of wall regeneration
      in soybean protoplasts.
AB  - Protoplasts isolated from cultured soybean cells (Glycine max (L.) Merr., cv.
      Mandarin) were used to study polysaccharide biosynthesis during the initial
      stages of cell wall-regeneration. Within minutes after the protoplasts were
      transferred to a wall-regeneration medium containing [(14)C]glucose,
      radioactivity was detected in a product which was chemically characterized as
      cellulose. The onset and accumulation of radioactivity into cellulose coincided
      with the appearance fibrils on the surface of protoplasts, as seen under the
      electron microscope. At these early stages, a variety of polysaccharide
      containing polymers other than cellulose were also synthesized. Under conditions
      where the protoplasts were competent to synthesize cellulose from glucose,
      uridine diphosphate-[(14)C]glucose and guanosine diphosphate-[(14)C]glucose did
      not serve as effective substrates for cellulose synthesis. However, substantial
      amounts of label from uridine diphosphate glucose were incorporated into 1,3
      glucan. 

PMID- 24302378
TI  - Light-promoted diffusional amino acid efflux from Commelina leaf disks : Indirect
      control by proton pump activities.
AB  - The release (=the measured loss) of amino acids was studied in Commelina
      benghalensis leaf disks. The release is assumed to be the result of influx and
      efflux, therefore, both movements were investigated.The uptake of (14)C-labeled
      valine exhibited a biphasic isotherm. The uptake was pH-dependent, especially at
      low substrate concentrations (pH optimum 4.8). Signals for amino acid/proton co
      transport were observed: stimulation of the uptake by fusicoccin (FC), inhibition
      by diethylstilbestrol (DES) or by high K(+) concentrations. In the light, the ATP
      level of the disks was maintained during the uptake period (2 h), in darkness the
      ATP content decreased from 87 to 24 nmol g(-1) fr. wt. However, light-promoted
      uptake, which is explained in the proton pump concept by an intensified proton
      extrusion as the result of high ATP production, was lacking.The release of amino
      acids was increased by washing with p-chloromercuriphenyl sulphonic acid (PCMBS),
      nystatin, 3(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), or KCN. The release (Q10
      about 1.5) was independent of the external pH and was linearly related to the
      intracellular amino acid concentration. Light enhanced the rate of release to the
      same extent at all intracellular concentrations. The present results suggest that
      the release is balanced by a, at least partially, proton-driven influx and a
      diffusional ligh-promoted efflux. A provisional model shows how the diffusional
      effulx can be indirectly controlled by a counter-flow fueled by the metabolism. 

PMID- 24302379
TI  - Modification of L-phenylalanine ammonia-lyase in soybean cell suspension cultures
      by 2-aminooxyacetate and L-2-aminooxy-3-phenylpropionate.
AB  - Suspension-cultured cells of soybean (Glycine max (L.) Merr. cv. Kanrich) produce
      large amounts of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), the first enzyme
      of phenylpropanoid metabolism, during growth. 2-Aminooxyacetic acid (AOA) and L-2
      aminooxy-3-phenylpropionic acid (L-AOPP) inhibit the enzyme competitively in
      vitro and have been used for in vivo studies. The amount of extractable enzyme in
      the cells and their utilization of NO 3 (-) and NH 3 (+) are reduced upon the
      addition of AOA. When AOA was added at various times during growth, the
      appearance of additional enzyme activity was prevented but enzyme already formed
      was not inhibited. No evidence was obtained for the presence of an inhibitor in
      the extracts and AOA inhibition in vitro was readily reversible. It is conculded
      that AOA acts to inhibit the formation of PAL in suspension-cultured soy bean
      cells. In vitro inhibition of soybean PAL by L-AOPP could not be reversed; in
      contrast, the inhibition of maize (Zea mays L.) PAL was readily reversible. Added
      L-AOPP, which was rapidly taken up by the soybean cells, prevented the large
      increase in enzyme activity. Although PAL activity was blocked in the cultures,
      no appreciable increase in phenylalanine content could be detected in cell
      extracts. The response of soybean cell suspensions to L-AOPP addition thus
      differs from that of other tissues which in presence of L-AOPP show an increase
      in PAL activity and an accumulation of phenylalanine. 

PMID- 24302380
TI  - Growth physics and water relations of red-light-induced germination in lettuce
      seeds : V. Promotion of elengation in the embryonic axes by gibberellins and
      phytochrome.
AB  - Red light (R) and gibberellins (GA) each induce a water potential decrease in the
      axes of lettuce (Lactuca sativa L.) embryos resulting in germination of intact
      "seeds" (achenes) or an increase in growth of the axes of isolated embryos. The
      fruit coat and endosperm are a substantial barrier to the penetration of
      exogeneous GA. Isolated embryos take up 35 times as much [(3)H]GA1 as the embryos
      of intact seeds and respond to less than 1.10(-10) M GA3 or GA4+7. We calculated
      that only 1.10(-8) M of either GA3 or GA4+7 would result in 50% germination if
      the GA were able freely to penetrate the fruit coat. Exogenous GA3 or GA4+7, at
      concentrations insufficient to cause germination, result in an apparent
      synergistic promotion of germination when suboptimal R is applied. Yet suboptimal
      concentrations of exogenous GA3 or GA4+7 and suboptimal R result in only additive
      increases in the growth response in axes of isolated embryos. Dose-response
      curves demonstrate quantitative increases in the growth response of the isolated
      axes after R or GA treatments insufficient to induce germination in intact seeds,
      indicating that a threshold potential must be achieved by the embryonic axes
      before germination can occur. 

PMID- 24302381
TI  - Synthesis of the intranuclear crystals in Scolopendrium vulgare (L.) SM : An
      autoradiographic study.
AB  - Proteinaceous intranuclear crystals are found in the fern Scolopendrium vulgare.
      During mitosis these crystals are eliminated from the nucleus into the cytoplasm,
      where they are dissolved. New crystals appear in the nucleus. The site of
      synthesis of intranuclear crystal proteins was investigated using quantitative
      ultrastructural autoradiography after incubation with tritiated lysine. The
      results suggest a migration of cytoplasmic proteins to the nucleus, part of which
      would then be incorporated into the intranuclear crystals. 

PMID- 24302382
TI  - An ultrastructural search for lectin-binding sites on surfaces of spinach leaf
      organelles.
AB  - Organelles isolated from leaves of spinach (Spinacia oleracea L.) were prefixed
      in glutaraldehyde and then incubated with ferritin conjugates of four lectins -
      Concanavalin A (Con A), Ricinus communis L. agglutinin, MW 120,000 (RCA), soybean
      agglutinin (SBA), and wheat germ agglutinin (WGA) - in order to probe their
      cytoplasmic surfaces for saccharide residues. In each case the major leaf
      organelles, including microbodies, mitochondria and chloroplast derivatives,
      failed to exhibit labeling when examined with the electron microscope. Tobacco
      (Nicotiana tabacum L.) leaf protoplasts, incubated simultaneously with and under
      identical conditions to the spinach organelles, showed specific labeling of their
      plasma membranes with all four lectin conjugates, thus establishing the efficacy
      of the procedure for demonstrating the presence of binding sites when they exist.
      Further attempts to show binding of one of the lectins, Con A, by labeling with
      fluorescein-Con A and by organelle agglutination, yielded results consistent with
      the absence of ultrastructural labeling. It is concluded that no saccharide
      residues recognized by the four lectins are present on the cytoplasmic surfaces
      of organelles and that those residues reported to be constituents of
      intracellular membranes, therefore, are most likely exposed on the luminal
      (extracytoplasmic) surfaces. 

PMID- 24302383
TI  - Determination of the membrane potential of vacuoles isolated from red-beet
      storage tissue : Evidence for an electrogenic ATPase.
AB  - The membrane potential of isolated vacuoles of red beet (Beta vulgaris L.) was
      estimated using several methods. The quenching of the fluorescence of the cyanine
      dyes 3,3'-diethylthiodicarbocyanine iodide (DiS-C2-(5)) and 3,3'
      dipropylthiodicarbocyanine iodide (DiS-C3-(5)) in vacuoles indicated a
      transmembrane potential difference, negative inside at low external potassium
      concentrations. The Deltapsi was found to be-55 mV with two other methods, the
      distribution of (204)T1(+) in the presence of valinomycin and the distribution of
      the lipophilic cation triphenylmethylphosphonium. Uncouplers reduced this value
      to-35 mV. High external potassium concentrations, comparable to cytosolic values,
      abolished the membrane potential almost completely. The addition of 1 mM Tris
      Mg(2+)-ATP markedly hyperpolarized the membrane to-75 mV. This effect was
      prevented by inhibitors of the ATPase activity located in isolated vacuole
      membranes. 

PMID- 24302384
TI  - Determination of femtomol quantities of gibberellic acid by radioimmunoassay.
AB  - A highly sensitive and specific radioimmunoassay which allows the detection of as
      little as 5 fmol (2 pg) of gibberellic acid (GA3) in crude plant extracts is
      described. Antisera of high affinity and titer were obtained by immunizing
      rabbits with a conjugate of carboxyl-coupled GA3 and bovine serum albumin.
      [(125)I]Gibberellic acid-[N-(p-hydroxybenzyl) putrescine]amide of high specific
      activity, used as the immunotracer, is readily displaced by gibberellic acid
      methyl ester but not by free gibberellic acid. Thus, methylation of extracts
      prior to analysis is required. The assay is very specific; besides GA3, only the
      closely related GA7 is highly immunoreactive. Various gibberellins, related
      compounds, as well as other classes of plant hormones do not interfere with the
      assay. Levels of immunoreactive gibberellins (GA3, GA7) in actively growing
      tissues, among them cell suspension cultures of 33 different species, were
      determined. 

PMID- 24302385
TI  - Determination of phytohormones in phloem exudate from tree species by
      radioimmunoassay.
AB  - A sensitive and specific radioimmunoassay was used to determine quantitatively
      four of the most important phytohormones in the phloem exudate from 14 different
      tree species of 8 genera. For cytokinins and indole-3-acetic acid (IAA) we found
      higher concentrations than those reported previously for other species. The
      gibberellin values were of the same order of magnitude as in earlier analyses
      (with different methods) of tree phloem exudates, but lower than the ones
      reported for Ricinus. Free abscisic acid (ABA) was found in tree phloem exudates
      in similar concentrations as before in Yucca or palm phloem exudate, but at
      considerably lower ones than reported for Ricinus and in Lupinus phloem exudate. 

PMID- 24302386
TI  - Biosynthesis and metabolism of L-ascorbic acid in virginia creeper
      (Parthenocissus quinquefolia L.).
AB  - Detached leaves of Parthenocissus quinquefolia L., Vitaceae convert D-glucose to
      L-ascorbic acid with conservation of the carbon chain sequence and with retention
      of the hydroxymethyl group at carbon 6. L-Ascorbic acid is cleaved between
      carbons 4 and 5. The C4 fragment is converted to L-tartaric acid. The C2
      fragment, possibly glycolaldehyde, recycles into products of hexose phosphate
      metabolism. During the metabolic period a relatively high portion of carbon-1 of
      L-ascorbic acid, as compared with carbon-4, was released as CO2. These studies
      demonstrate the usefulness of Virginia Creeper for yeararound research on
      ascorbic-acid metabolism and tartaric-acid biosynthesis in Vitaceae-type plants. 

PMID- 24302387
TI  - Testing for qualitative interaction using ratios of treatment differences.
AB  - Testing for or against a qualitative interaction is relevant in randomized
      clinical trials that use a common primary factor treatment and have a secondary
      factor, such as the centre, region, subgroup, gender or biomarker. Interaction
      contrasts are formulated for ratios of differences between the levels of the
      primary treatment factor. Simultaneous confidence intervals allow for
      interpreting the magnitude and the relevance of the qualitative interaction. The
      proposed method is demonstrated by means of a multi-centre clinical trial, using
      the R package mratios.

PMID- 24302388
TI  - Effect of increased quadriceps tensile stiffness on peak anterior cruciate
      ligament strain during a simulated pivot landing.
AB  - ACL injury prevention programs often involve strengthening the knee muscles. We
      posit that an unrecognized benefit of such training is the associated increase in
      the tensile stiffness of the hypertrophied muscle. We tested the hypothesis that
      an increased quadriceps tensile stiffness would reduce peak anteromedial bundle
      (AM-)ACL relative strain in female knees. Twelve female cadaver knees were
      subjected to compound impulsive two-times body weight loads in compression,
      flexion, and internal tibial torque beginning at 15 degrees  flexion. Knees were
      equipped with modifiable custom springs to represent the nonlinear rapid stretch
      behavior of a normal and increased stiffness female quadriceps (i.e., 33% greater
      stiffness). Peak AM-ACL relative strain was measured using an in situ transducer
      while muscle forces and tibiofemoral kinematics and kinetics were recorded. A 3D
      ADAMSTM dynamic biomechanical knee model was used in silico to interpret the
      experimental results which were analyzed using a repeated-measures Wilcoxon test.
      Female knees exhibited a 16% reduction in peak AM-ACL relative strain and 21%
      reduction in change in flexion when quadriceps tensile stiffness was increased by
      33% (mean (SD) difference: 0.97% (0.65%), p = 0.003). We conclude that increased
      quadriceps tensile stiffness reduces peak ACL strain during a controlled study
      simulating a pivot landing.

PMID- 24302389
TI  - Cyanogenesis-a general phenomenon in the lepidoptera?
AB  - There are two different pathways known to be used for the detoxification of
      hydrocyanic acid in insects, viz., rhodanese and beta-cyano-L-ala-nine synthase.
      We consider the latter to be indicative for cyanogenesis, while rhodanese might,
      in general, play a more important role in sulfur transfer for protein synthesis.
      This paper reports on the distribution of beta-cyano-L-alanine (BCA) in the
      Lepidoptera. First reports of cyanogenesis are presented for the following
      families: Papilionidae, Pieridae, Lycaenidae, Hesperiidae, Lymantriidae,
      Arctiidae, Notodontidae, Megalopygidae, Limacodidae, Cymatophoridae, Noctuidae,
      Geometridae, and Yponomeutidae. New and old records for three other families, the
      Nymphalidae, Zygaenidae, and Heterogynidae, are included to complete the present
      state of knowledge. Special emphasis has been laid on the Nymphalidae, where BCA
      has been detected in eight subfamilies. Taxonomic, geographic, and seasonal
      variation has been found in a number of cases. In all cases observed so far, the
      source of cyanogenesis in the Lepidoptera is most probably the cyanoglucosides
      linamarin and lotaustralin, although cyanogenesis based on mustard oil glucosides
      and cyclopentenoid glucosides might occur as well. BCA has been found in both
      cryptic and aposematic species, including taxa such as the Pieridae, Danainae,
      Ithomiinae, and Arctiidae, where the defensive biology is believed to be linked
      with other compounds, like mustard oil glucosides, cardenolides, or pyrrolizidine
      alkaloids. The ecological interaction and significance of such secondary
      compounds is not yet understood. 

PMID- 24302390
TI  - Novel pyrazines from the head of Australian ponerine antRhytidoponera metallica.
AB  - The novel pyrazines, (E)- and (Z)-5-methyl-3-(2-methylbutyl)-2-(3-methylbut-1
      enyl)pyrazine, (E)- and (Z)-5-methyl-3-isopentyl-2-(3-methylbut-1-enyl) pyrazine,
      (E)- and (Z)-5-methyl-3-(2-methylbutyl)-2-(3-methylpent-1-enyl)pyrazine, (E)- and
      (Z)-5-methyl-3-isopentyl-2-(3-methylpentl-enyl) pyrazine, together with the known
      pyrazines, 2,5-dimethyl-3-(2-methylbutyl)pyrazine and 2,5-dimethyl-3
      isopentylpyrazine, have been identified from the head of the Australian ponerine
      antRhytidoponera metallica. Alkanes and alkenes, in small amounts, were also
      detected. 

PMID- 24302391
TI  - Evidence of pheromonal constancy among sexual and asexual females in a population
      of fall cankerworm,Alsophila pometaria (Lepidoptera: Geometridae).
AB  - The compounds (Z,Z,Z)-3,6,9-nonadecatriene (I), (Z,Z,Z,E)-(II), and (Z,Z,Z,Z)
      3,6,9,11-nonadecatetraene (III) have been implicated as components of the female
      sex pheromone of the fall cankerworm. Chromatographie determination of the
      proportions of these compounds in individual females of sympatric asexual and
      sexual reproductive forms of the species, with concurrent analysis of the
      electrophoretic profiles of the same females, showed that the I: II: III
      proportion of compounds was constant across electrophoretically differing asexual
      genotypes and between these and the sexual form. Life-history characters, in
      contrast, typically show great variation among these genetic groups. The results
      indicate that pheromonal constancy is maintained in a reproductive system that is
      theoretically vulnerable to selective pressures that would lead to heterogeneity
      in the species' pheromonal communication channel. 

PMID- 24302392
TI  - Discrimination of occupied host fruit by plum curculio females (Coleoptera:
      Curculionidae).
AB  - Larval survival of plum curculios (PCs),Conotrachelus nenuphar (Herbst), was
      found to decrease with increasing egg density per fruit. Subsequently, we assayed
      PCs for propensity to avoid egg-laying at sites (immature plums) already occupied
      by conspecific eggs. Laboratory choice tests showed PCs made an equal number of
      visits to and ovipositions in fruit with a single oviposition as in clean fruit.
      Although there was a trend toward more visits to fruit which contained four or
      eight oviposition wounds and eggs or eight artificial punctures than to clean
      fruit, PCs oviposited less frequently into these than clean fruit. Results
      suggest that wounding of fruit may enhance the ability of ovipositing PCs to
      locate fruit, but at the same time may furnish cues allowing some degree of
      discrimination against heavily infested fruit for oviposition. 

PMID- 24302393
TI  - Presence of pterin pigments in wings of libytheidae butterflies.
AB  - A few pterin pigments were discovered in the wings of six of eight libytheid
      species tested, using thin-layer chromatography with 1 % HC1 in butanol as a
      solvent. A 10X sample ofLibytheana bachmanii larvata (Strecker) produced
      xanthopterin, isoxanthopterin, erythropterin, and leucopterin. Leucopterin was
      absent in the other libytheids tested. Morphology and pterin pigment data from
      wings suggest a Pieridae ancestry for the Libytheidae from the region of the
      northern Neotropical realm (including the Greater Antilles). 

PMID- 24302394
TI  - Heliothis subflexa (Gn.) (Lepidoptera: Noctuidae): Demonstration of oviposition
      stimulant from groundcherry using novel bioassay.
AB  - Methanol extracts of homogenized groundcherry,Physalis angulata, leaves increased
      egg deposition byHeliothis subflexa (Gn.) (HS) on treated tobacco plants (a
      nonhost) 8.5-fold over untreated controls. In doseresponse tests using whole-leaf
      washes of groundcherry leaves, the threshold of positive response vs. no response
      to the chemical stimulant was within one log dose unit when compared to the
      controls. This response was consistent whether the chemical was evaluated on
      plants in greenhouse-cage tests or in an olfactometer using pieces of broadcloth
      as the oviposition substrate. The olfactometer used allows year-round study of
      the behavioral effects of plant allelochemics on insect oviposition behavior in a
      controlled environment. 

PMID- 24302395
TI  - Inhibition of male response of drugstore beetles to stegobinone by its isomer.
AB  - Stegobinone, (2S, 3R, 1'R)-2,3,-dihy dro-2,3,5-trimethyl-6-(1'-methyl-2'
      oxobutyl)-4H-pyran-4-one, the sex pheromone of drugstore beetles (Stegobium
      paniceum L.), elicited the pheromonal response from the males of the species in
      our bioassay system; however, the synthesized diastereomeric mixture of this
      compound was actually inactive to the males. Although the stegobinone isolated
      from the beetles of this species had significant activity, its enantiomeric [(+/
      )-2S,3R,1'S-] and diatereomeric [(+/-)-2S,3S,1'RS-] isomers were inactive. Adding
      the (+/-)-2S,3R,1'S isomer to stegobinone significantly reduced the male
      response. Furthermore, the activity of Stegobinone vanished on keeping it at room
      temperature for two weeks. In such a stored stegobinone sample, the presence of
      2S,3R,1'S isomer, the inhibitory component, was confirmed. This isomer might be
      produced by C-1' epimerization during storage. 

PMID- 24302396
TI  - Stegobiol, a new sex pheromone component of drugstore beetle (Stegobium paniceum
      L.).
AB  - New sex pheromone component of femaleStegobium paniceum L. was isolated and
      identified as 2,3-dihydro-2,3,5-trimethyI-6-(1'-methyl-2'-hydroxybutyl)-4H-pyran
      4-one, stegobiol, by spectral data and chemical conversion from stegobinone.
      Relative configuration at C-2, C-3, and C-1' was determined as 2S,3R,1'S by the
      conversion from (2S,3R,1'R)-stegobinone. This new sex pheromone elicits the
      pheromonal response from the species. 

PMID- 24302397
TI  - Allelopathy in agroecosystems: Wheat phytotoxicity and its possible roles in crop
      rotation.
AB  - The germination rates of cotton and wheat seeds were significantly affected by
      various extracts of wheat mulch and soils collected from the wheat field. This
      toxicity was even more pronounced against seedling growth. Five allelochemics:
      ferulic,p-coumaric,p-OH benzoic, syringic, and vanillic acids, were identified
      from the wheat mulch and its associated soil. Quantitatively, ferulic acid was
      found at higher concentrations thanp-coumaric acid in the soil. Various
      concentrations of ferulic andp-coumaric acids were toxic to the growth of radish
      in a bioassay. The functional aspects of allelochemic transfer from decaying
      residue to soil and the subsequent microbial degradation within agroecosystems
      are discussed, particularly as they relate to wheat crop rotation, with wheat and
      cotton, in Pakistan. 

PMID- 24302398
TI  - Olfactory responses of a specialist and a generalist grasshopper to volatiles
      ofArtemisia ludoviciana nutt. (Asteraceae).
AB  - Hypochlora alba is a specialist grasshopper that lives and feeds almost
      exclusively onArtemisia ludoviciana, a plant that produces large amounts of
      allelochemics including a variety of monoterpenes. This plant is not a host for
      generalist grasshoppers such asMelanoplus sanguinipes. The role of olfaction in
      the grasshopper-plant relationship was investigated by comparing
      electroantennograms (EAGs) of males and females of both species generated by
      solvent-extracted volatiles from plant leaves and by major individual components.
      Volatiles ofA. ludoviciana were identified by gas chromatography-mass
      spectrometry. The major components were 1,8-cineole, camphor, camphene, and
      borneol, while minor identified compounds were alpha- and beta-pinene, alpha
      thujene, myrcene,p-cymene, Artemisia ketone, alpha-thujone, and bornyl acetate.
      The EAGs (mV) ofH. alba males to a range of concentrations of individual
      volatiles or the total plant extract were nearly double those of conspecific
      females or both sexes ofM. sanguinipes. However, both sexes ofM. sanguinipes were
      more sensitive than either sex ofH, alba to geraniol, a monoterpene that commonly
      occurs in many plant species but is absent or is present in only trace amounts
      inA. ludoviciana. The increased sensitivity ofH. alba males to the odor
      components of their host plant appears to be related to the greater number of
      certain olfactory chemoreceptors on male versus female antennae. The significance
      of this phenomenon is discussed. 

PMID- 24302399
TI  - Behavioral and physiological responses of cabbage looper,Trichoplusia ni
      (Hubner), to steam distillates from resistant versus susceptible soybean plants.
AB  - Soybean plant volatiles, extracted as steam distillates, significantly affected
      the behavior and biology of the cabbage looper,Trichoplusia ni (Hubner)
      (Lepidoptera: Noctuidae). Distillates from the susceptible Davis variety
      attractedT. ni larvae and female adults, whereas those from resistant PI 227687
      plants repelled them. When mixed in an artificial diet, steam distillates from PI
      227687 plants caused mortality of first-instar larvae. Adults emerging from pupae
      topically treated with 5 MUg of such PI 227687 extractable showed developmental
      abnormalities. Larval feeding was significantly less on Davis leaves treated with
      PI 227687 volatiles as compared to solvent (acetone) or such Davis extractables.
      However, Davis volatiles on PI 227687 leaves did not increase larval feeding.
      HPLC analyses of steam distillates from susceptible Davis versus resistant PI
      227687 indicated differences. 

PMID- 24302400
TI  - Transfer of pyrrolizidine and quinolizidine alkaloids toCastilleja
      (Scrophulariaceae) hemiparasites from composite and legume host plants.
AB  - Castilleja (Scrophulariaceae) species of the western United States contain
      pyrrolizidine and quinolizidine alkaloids. TheCastilleja obtain the alkaloids by
      root parasitism on host plants, withSenecio atratus andS. triangularis
      (Asteraceae) furnishing the pyrrolizidines, and quinolizidines being obtained
      fromLupinus species andThermopsis montana (Leguminosae). Individual plants within
      a givenCastilleja species population may be devoid of alkaloids while others have
      high alkaloid content. No populations have been found which are made up of both
      pyrrolizidine- and quinolizidine-containing individuals. These results have
      important implications forCastilleja ecology, for the study of insect herbivores
      which areCastilleja specialists, and in the development of systems for the
      investigation of the role of alkaloids as plant defenses. 

PMID- 24302401
TI  - Preparation of 8-methyl-2-decanol: General synthesis of diastereomeric mixtures
      of alkyl branched insect pheromones.
AB  - A general method for synthesis of insect pheromones having alkyl branched carbon
      skeletons is demonstrated with the preparation of a diastereomeric mixture of 8
      methyl-2-decanol, whose propionate is an attractant of someDiabrotica species.
      The procedure involves reaction of a ketone with lithium acetylide
      ethylenediamine complex to afford a propargylic alcohol containing the branch of
      the target molecule. Copper (1) mediated alkylation of the derived propargylic
      acetate with a primary alkyl halide yields a trisubstituted allene having the
      desired chain length, and isomerization with an alkali metal amide of either
      ethylenediamine or 1,3-diaminopropane, affords the alkyl branched terminal
      acetylene. The triple bond is converted to the methyl ketone and reduced to the
      methyl carbinol. The reactions proceed in good yield, and can be conveniently
      carried out on large scale. The method should prove useful for production of
      pheromone components in cases where diastereomeric mixtures can be employed. 

PMID- 24302402
TI  - Expression of alcohol dehydrogenase in rice embryos under anoxia.
AB  - Alcohol dehydrogenase (ADH) activity was present in roots and shoots of 48-h rice
      embryos and rose in response to anoxia. The increase was accompanied by changes
      in the ADH isozyme pattern. Translatable levels of mRNA for two ADH peptides
      increases as early as 1 h after the beginning of anoxic treatment. Adh mRNA was
      detected in aerobically grown rice embryos by hybridization to maize Adh1 cDNA:
      its level increased significantly after 3 h of anoxia. 

PMID- 24302403
TI  - Organellar DNA synthesis in permeabilized soybean cells.
AB  - Cultured cells of Glycine max (L.) Merr. v. Corsoy were permeabilized by
      treatment with L-alpha-lysophosphatidylcholine (LPC). The permeabilized cells
      were capable of uptake and incorporation of deoxynucleoside triphosphates into
      DNA. Incorporation of exogenous nucleotides into DNA was linear for at least 90
      minutes and the initial rate of incorporation approached 50% of the theoretical
      in vivo rate of DNA synthesis. However, DNA synthesis in the permeabilized cells
      was unaffected by the potent DNA polymerase alpha inhibitor, aphidicolin.
      Analysis of newly synthesized DNA by molecular hybridization revealed that only
      organellar DNA was synthesized by the permeabilized cells. The LPC treated cells
      were also permeable to a protein as large as DNase I. The permeabilized cells
      were capable of RNA and protein synthesis as indicated by incorporation of
      radiolabeled UTP and leucine, respectively, into acid-precipitable material. 

PMID- 24302404
TI  - Structural differences in full-length cDNAs for two classes of sporamin, the
      major soluble protein of sweet potato tuberous roots.
AB  - Sporamin, which accounts for 80% of the total soluble proteins in sweet potato
      tuberous roots, consists of two polypeptide classes, A and B. The sporamin cDNA
      clones can also be classified into sporamin A and B subfamilies based on their
      sequence homologies, with intra-subfamily homologies being much higher than inter
      subfamily homologies. The sequence of an essentially full-length cDNA for
      sporamin B was compared with that for sporamin A. The coding sequences of two
      cDNAs share 83% sequence homology. The sequences in the 5'- and 3'-noncoding
      regions show many deletions in addition to base substitutions. The endpoints of
      deletions longer than 4 bp match precisely to the endpoints of short direct
      repeats present in the other sequence, which suggests that these deletions are
      generated by slipped mispairing during DNA replication. In the 5'- and 3'
      noncoding region of sporamin B cDNA, there are 5 bp direct repeats with sequences
      complementary to each other. Since most of these repeats are absent in sporamin A
      cDNA, these structural features may cause a difference in the secondary structure
      between A and B mRNAs and affect the translational efficiencies or stabilities of
      the mRNAs. Precursors for both classes of sporamin carry N-terminal extra
      sequences which can be separated into a putative signal peptide segment and a
      segment enriched with basic amino acids. A two-step processing mechanism for the
      maturation of sporamin is suggested. 

PMID- 24302405
TI  - A set of novel Ti plasmid-derived vectors for the production of transgenic
      plants.
AB  - We describe in this paper the construction and use of a set of novel Ti plasmid
      derived vectors that can be used to produce transgenic plants. These vectors are
      based on one of two strategies: 1) double recombination into the wild-type Ti
      plasmid of genetic information flanked by two T-DNA fragments on a wide-host
      range plasmid; 2) the binary vector strategy. The vector based on the double
      recombination principle contains a kanamycin resistance gene for use as a plant
      selectable marker, a polylinker for the insertion of foreign genes, and a
      nopaline synthase gene. The vector was constructed such that a disarmed T-DNA
      results from the double recombination event. The binary vector combines several
      advantageous features including an origin of replication that is stable in
      Agrobacterium in the absence of selection, six unique sites for insertion of
      foreign genes, an intact nopaline synthase gene, and a kanamycin resistance
      marker for selection of transformed plant cells. All of these vectors have been
      used to produce tobacco plants transformed with a variety of foreign genes. 

PMID- 24302406
TI  - Expression of nuclear and plastid genes for photosynthesis-specific proteins
      during tomato fruit development and ripening.
AB  - The expression of plastid and nuclear genes coding for photosynthesis-specific
      proteins has been studied during tomato fruit formation. The steady-state
      transcript levels for the large (rbcL) and small (rbcS) subunit of RuBPC/Oase, as
      well as the thylakoid membrane proteins, the 32 kD QB-binding protein of PS II
      (psbA), the P700 reaction center protein of PS I (psaA) and the chlorophyll a/b
      binding protein (cab) vary at different time points during fruit development and
      ripening. Messenger RNA levels of plastid-encoded photosynthesis-specific genes
      (rbcL, psbA) are at least several fold higher, relative to respective nuclear
      encoded genes (rbcS, cab). The transcript levels for the large and small subunit
      of RuBPC/Oase are highest in approximately 14-day-old tomato fruits, while the
      chl a/b-binding protein, the P700 reaction center protein and the 32 kD QB
      binding protein reach their maxima in approximately 7-, 14- and 25-day-old tomato
      fruits, respectively. The inactivation of the photosynthesis-specific genes
      occurs during the first period of fruit formation. In addition, there is
      considerable variation in the mRNA levels of these photosynthesis-specific genes
      in four organs of tomato (leaves, fruits, stems, roots). 

PMID- 24302407
TI  - Nucleotide sequence of the cytochrome oxidase subunit I gene from soybean
      mitochondria.
AB  - The cytochrome oxidase subunit I gene was isolated from a soybean mitochondrial
      library and subcloned into M13 for DNA sequencing. The sequences of the gene and
      flanking regions are presented and compared to the corresponding gene from maize.
      There is approximately 94% sequence homology between the soybean (dicot) and
      maize (monocot) coding sequences at the nucleotide level. The soybean sequence
      exists as a single copy in the mitochondrial genome and contains an open reading
      frame that could encode a polypeptide of 527 amino acids. There is very little
      sequence homology between the soybean and maize sequences upstream from the
      coding regions and none is detected downstream. Even the 3' ends of the COI
      coding regions differ considerably between soybean and maize. There are many
      amino acid differences at the carboxy terminus and the predicted polypeptide
      contains one less amino acid than the maize sequence. Northern analysis of the
      soybean mitochondrial RNA suggests that this region is actively transcribed and
      yields two major transcripts. 

PMID- 24302408
TI  - Structures of tobacco chloroplast genes for tRNA(Ile) (CAU), tRNA (Leu) (CAA),
      tRNA (Cys) (GCA), tRNA (Ser) (UGA) and tRNA (Thr) (GGU): a compilation of tRNA
      genes from tobacco chloroplasts.
AB  - The location and nucleotide sequences of tobacco chloroplast genes for tRNA(Ile)
      (CAU), tRNA(Leu) (CAA), tRNA(Cys) (GCA), tRNA(Ser) (UGA) and tRNA(Thr) (GGU)
      (trnI-CAU, trnL-CAA, trnC-GCA, trnS-UGA and trnT-GGU, respectively) have been
      determined. The trnI and trnL are located in the inverted repeat region. The
      trnC, trnS and trnT are present in the large single copy region. These five tRNA
      genes together with the 25 different tRNA genes previously published have been
      compiled and compared. These 30 tRNA genes corresponding to 20 amino acids are
      most likely to be all of the tRNA genes encoded in tobacco chloroplast genome. 

PMID- 24302410
TI  - Contents volume 4 (1985).

PMID- 24302409
TI  - In maize, glutelin-2 and low molecular weight zeins are synthesized by membrane
      bound polyribosomes and translocated into microsomal membranes.
AB  - Experiments to establish the site of biosynthesis and the possible translocation
      into microsomes of glutelins-2 (28 kD G2) and low molecular weight zeins (10, 14,
      15 kD Z2) have been carried out. Free and membrane-bound polyribosomes as well as
      microsomal membranes were isolated from immature endosperms of W64A Zea mays L.
      In vitro translation studies were carried out in the presence and in the absence
      of membranes using [(35)S]-methionine or [(35)S]-cysteine as precursors. Cell
      free translation products were characterized by electrophoretic mobility,
      solubility and antigenic properties. The results obtained indicate that 28 kD G2
      and low molecular weight zeins are primarily synthesized on membrane-bound
      polysomes. From experiments using proteinase K as a probe, we also conclude that
      these proteins are translocated into microsomes where they accumulate. The
      translocated and pre-28 kD G2 proteins do not present changes in the apparent
      molecular weight. However we show that there are differences in their isoelectric
      points, a fact that indicates the existence of 28 kD G2 processing. 

PMID- 24302411
TI  - Is HPV DNA testing specificity comparable to that of cytological testing in
      primary cervical cancer screening? Results of a meta-analysis of randomized
      controlled trials.
AB  - Human-papillomavirus (HPV) DNA testing has been proposed as an alternative to
      primary cervical cancer screening using cytological testing. Review of the
      evidence shows that available data are conflicting for some aspects. The overall
      goal of the study is to update the performance of HPV DNA as stand-alone testing
      in primary cervical cancer screening, focusing particularly on the aspects
      related to the specificity profile of the HPV DNA testing in respect to cytology.
      We performed a meta-analysis of randomized controlled clinical trials. Eight
      articles were included in the meta-analysis. Three outcomes have been
      investigated: relative detection, relative specificity, and relative positive
      predictive value (PPV) of HPV DNA testing versus cytology. Overall evaluation of
      relative detection showed a significantly higher detection of CIN2+ and CIN3+ for
      HPV DNA testing versus cytology. Meta-analyses that considered all age groups
      showed a relative specificity that favored the cytology in detecting both CIN2+
      and CIN3+ lesions whereas, in the >=30 years' group, specificity of HPV DNA and
      cytology tests was similar in detecting both CIN2+ and CIN3+ lesions. Results of
      the pooled analysis on relative PPV showed a not significantly lower PPV of HPV
      DNA test over cytology. A main key finding of the study is that in women aged
      >=30, has been found an almost overlapping specificity between the two screening
      tests in detecting CIN2 and above-grade lesions. Therefore, primary screening of
      cervical cancer by HPV DNA testing appears to offer the right balance between
      maximum detection of CIN2+ and adequate specificity, if performed in the age
      group >=30 years. 

PMID- 24302412
TI  - Concanavalin A binds to the endoplasmic reticulum and the starch grain surface of
      root statocytes.
AB  - Using Concanavalin A (Con A) labeled with fluorescein isothiocyanate, we studied
      the intracellular localization of receptor molecules in the calyptra of 24-h dark
      grown cress roots. Fixation in glutaraldehyde gave positive binding of the distal
      complex of the endoplasmic reticulum and the nucelus in the statocytes. In
      contrast, fixation in formaldehyde did not preserve the membrane-associated
      receptors, but revealed Con A affinity of the starch grain surface within the
      amyloplasts. Treatment of glutaraldehydefixed sections with non-ionic detergents
      led to partial solubilization of membrane components: the starch grain surface
      turned positive, though the positive binding of Con A to the endoplasmic
      reticulum and the nucleus remained unaffected. We therefore conclude that the Con
      A receptor in the membrane is a glycoprotein tightly inserted in other components
      of the compartment. 

PMID- 24302413
TI  - Crassulacean acid metabolism (CAM) in Kalanchoe daigremontiana: Temperature
      response of phosphoenolpyruvate (PEP)-carboxylase in relation to allosteric
      effectors.
AB  - Net CO2 dark fixation of Kalanchoe daigremontiana varies with night temperature.
      We found an optimum of fixation at about 15 degrees  C; with increasing night
      temperature fixation decreased. We studied the temperature dependence of the
      activity of phosphoenolpyruvate (PEP)-carboxylase, the key enzyme for CO2 dark
      fixation. We varied the pH, the substrate concentration (PEP), and the L-malate
      and glucose-6-phosphate (G-6-P) concentration in the assay. Generally, lowering
      the pH and reducing the amount of substrate resulted in an increase in activation
      by G-6-P and in an increase in malate inhibition of the enzyme. Furthermore,
      malate inhibition and G-6-P activation increased with increasing temperature.
      Activity measurements between 10 degrees  C and 45 degrees C at a given
      concentration of the effectors revealed that the temperature optimum and maximum
      activities at that optimum varied with the effector applied. Under the influence
      of 5 mol m(-3) L-malate the temperature optimum and maximum activity dropped
      drastically, especially when the substrate level was low (at 0.5 mol m(-3) PEP
      from 32 degrees  C to 20 degrees  C). G-6-P raised the temperature optimum and
      maximum activity when the substrate level was low. If both malate and G-6-P were
      present, intermediate values were measured. We suggest that changes in metabolite
      levels in K. daigremontiana leaves can alter the temperature features of PEP
      carboxylase so that the observed in vivo CO2 dark fixation can be explained on
      the basis of PEP-carboxylase activity. 

PMID- 24302414
TI  - Adenine nucleotides and energy charge evolution during the induction of flowering
      in spinach leaves.
AB  - Changes in adenine nucleotides pool size levels have been investigated in spinach
      leaves (Spinacia oleracea. L. cv. Nobel) in order to characterize the transition
      from the vegetative to the reproductive development. The transient changes
      reported in this study are the earliest responses observed to date in leaves
      during photoperiodic induction. These results are discussed in relation to
      Prigogine's theory of systems far from equilibrium. 

PMID- 24302415
TI  - Identification and quantitation of adenosine-3':5'-cyclic monophosphate in plants
      using gas chromatography-mass spectrometry and high-performance liquid
      chromatography.
AB  - Direct evidence has been obtained for the presence of adenosine-3':5'-cyclic
      monophosphate (cAMP) in tobacco (Nicotiana tabacum L.) callus tissue cultures,
      bean (Phaseolus vulgaris L.) seedlings and immature kernels of sweet corn (Zea
      mays L.) through the use of a highly specific and sensitive gas chromatography
      mass spectrometric assay. Levels of endogenous cAMP ranged from 70 to 126 pmol/g
      fresh weight. Corresponding levels of cAMP determined for the same samples using
      radioimmunoassay were consistently three to four times higher. Contrary to
      previous reports for citrus plants, measurable levels of cAMP could not be
      detected in young lemon leaves within the limits of detection of the mass
      spectrometric assay method. In the case of tobacco callus tissue, the coumarin
      glucoside, scopolin, which was present in large amounts and showed similar
      chromatographic behaviour to cAMP, interferred strongly with the mass
      spectrometric measurements of cAMP in inadequately purified extracts. The use of
      high-performance liquid chromatography, in addition to standard chromatographic
      purification methods, produced highly purified plant extracts for quantitation of
      cAMP and also provided a method for the separation of cAMP from its 2':3'-isomer.

PMID- 24302416
TI  - Tributylbenzylammonium (TBBA(+))-dependent fusicoccin (FC)-induced H(+) extrusion
      in maize roots: relationship between the stimulating effects of TBBA(+) on H (+)
      extrusion and on Cl (-) efflux.
AB  - The mechanism of the stimulating effect of lipophilic cations on H(+) extrusion
      in maize root segments (Zea mays L.) has been investigated. The measurement of
      the uptake of [(3)H]tributylbenzylammonium ([(3)H]TBBA(+)), the most active
      lipophilic cation on H(+) extrusion, indicated that although a relevant fraction
      of TBBA(+) taken up by the tissue is adsorbed to cell surfaces, a fraction of the
      cation enters the cells. However no correlation was observed between the rate of
      TBBA(+) uptake and that of H(+) extrusion. On the other hand, the lipophilic
      cations active on H(+) extrusion (TBBA(+) and dibenzyldimethylammonium (DDA(+))),
      in the presence of fusicoccin (FC), induced under the same conditions an efflux
      of Cl(-), while tetramethylammonium (TMA(+)), inactive on H(+) extrusion, did
      not. The stimulation of Cl(-) efflux by TBBA(+) was independent of the anion
      present in the medium and was inhibited by Na-orthovanadate, an inhibitor of
      plasma membrane ATPase and of TBBA(+)-induced H(+) extrusion. These results
      suggest that the stimulation of H(+) extrusion by TBBA(+) depends on its effect
      on Cl(-) efflux rather than on its penetration into the cells. 

PMID- 24302417
TI  - Interaction of light and temperature on the germination of Rumex obtusifolius L.
AB  - Seeds (nutlets) of Rumex obtusifolius L. fail to germinate in darkness at 25
      degrees  C, but are stimulated by short exposure to red light (R) the
      effectiveness of which can be negated by a subsequent short exposure to far red
      light (F) indicating phytochrome control. Short periods of elevated temperature
      treatment (e.g. 5 min at 35 degrees  C) can induce complete germination in
      darkness. Although short F cannot revert the effect of 35 degrees  C treatment,
      cycling the phytochrome pool by exposure to short R before short F results in
      reversion of at least 50% of the population. Prolonged or intermittent F can also
      revert the germination induced by 35 degrees  C treatment. The effect of elevated
      temperature treatment is interpreted on the basis of two possible models; (i)
      that it increases the sensitivity of the seeds to a low level of pre-existing
      active form of phytochrome (Pfr) (ii) that it induces the appearance of Pfr in
      the dark. In both cases it is envisaged that elevated temperature treatment and
      Pfr control germination at a common point in the series of reactions that lead to
      germination. 

PMID- 24302418
TI  - DNA synthesis in cytokinin-autotrophic tobacco cells : Effect of
      bromodeoxyuridine, fluorodeoxyuridine, and kinetin.
AB  - DNA isolated from various Nicotiana tabacum cell types, differing in their degree
      of hormone autotrophy and incubated in the presence of bromodeoxyuridine
      (BrdUrd), was analyzed by isopycnic CsCl gradient centrifugation. All cell types
      incorporate BrdUrd into DNA in such a way that hybrid DNA is formed with 60-80%
      of thymine (Thy) residues replaced by bromouracil (BrUra) in the newly
      synthesized strand. This DNA is not replicated further under ordinary culture
      conditions. Whereas in "normal" hormone-dependent cells this state is final and
      cells necrotize, in tumor (cytokinin-auxin autotrophic) and cytokinin-autotrophic
      cells a mechanism is induced leading to the reduction of BrUra content in DNA. As
      a result a decrease in the buoyant density (in CsCl) of BrUra DNA can be
      observed. In the case of cytokinin-autotrophic cells supplemented with kinetin,
      the buoyant density of the whole DNA decreases gradually to the value of that of
      unsubstituted DNA, but specific radioactivities of different DNA fractions
      reflect the retention of the pyrimidine ring of BrUra in DNA. This is interpreted
      as debromination of DNA in situ. The process can be inhibited by
      fluorodeoxyuridine (FdUrd) and deoxycytidine (dCyd). Moreover, FdUrd (but not
      dCyd) allows replication of hybrid DNA in tumor cells in such a way that HH DNA
      with all Thy residues replaced by BrUra is formed. For cytokinin-autotrophic
      cells FdUrd and kinetin are required. In hormone-dependent cells replication of
      hybrid DNA cannot be induced under any conditions. Most of these conclusions
      complement our previous findings that BrdUrd tolerance in hormone-autotrophic
      tobacco cells in hormone controlled. It is postulated that a modulation of
      thymidylate synthetase specificity is one factor affecting the level of BrUra
      substitution in DNA. The possibility of cytokinins being involved in the control
      of DNA synthesis is discussed. 

PMID- 24302419
TI  - Control of hemicellulose and pectin synthesis during differentiation of vascular
      tissue in bean (Phaseolus vulgaris) callus and in bean hypocotyl.
AB  - Membrane fractions from bean hypocotyl or callus incorporate arabinose from UDP
      beta-L-arabinose into arabinan and xylose from UDP-alpha-D-xylose into xylan. The
      control of these syntheses has been studied during xylogenesis in stele and in
      xylogenesis induced in callus tissue. Induction of arabinan synthetase activity
      occurs during division and extension growth while that of xylan synthetase occurs
      subsequently during the period of secondary thickening of the cell wall. The
      xylan synthetase induction is correlated with the induction of phenylalanine
      ammonia-lyase and with lignin synthesis. 

PMID- 24302420
TI  - Role of ATP in nitrite reduction in roots of wheat and pea.
AB  - Excised wheat (Triticum aestivum L.) and field pea (Pisum arvense L.) roots,
      incubated under anaerobic conditions or in the presence of uncouplers of
      oxidative phosphorylation [2,4-dinitrophenol (DNP), carbonylcyanide-m
      chlorophenylhydrazone, pentachlorophenol] accumulated nitrite as a result of an
      inhibition of nitrite reduction. In isolated root plastids, nitrite reduction was
      dependent on a supply of glucose-6-phosphate (G6P) and did not require ATP. The
      estimated Km value for glucose 6-phosphate was 1.25 mM. Glucose and fructose-1,6
      diphosphate were ineffective substrates for nitrate reduction. Anaerobic
      conditions and treatment with DNP, which would result in a cessation of ATP
      production by the mitochondria and a stimulation of glycolysis via the "Pasteur
      effect", were shown to decrease the G6P content of excised roots of wheat and
      pea. A negative correlation was observed between the level of G6P and nitrite
      accumulation on root tissues. It is proposed that an interruption in the supply
      of G6P to the root plastid under these conditions would result in an inhibition
      of nitrite reduction leading to nitrite accumulation. 

PMID- 24302421
TI  - Correlations between proton-efflux patterns and growth patterns during geotropism
      and phototropism in maize and sunflower.
AB  - By placing seedlings of sunflower (Helianthus annuus L.) or maize (Zea mays L.)
      on agar plates containing a pH indicator dye it is possible to observe surface pH
      patterns along the growing seedling by observing color changes of the indicator
      dye. Using this method we find that in geotropically stimulated sunflower
      hypocotyls or maize coleoptiles there is enhanced proton efflux on the lower
      surface of the organ prior to the initiation of curvature. As curvature develops
      the pattern of differential acid efflux becomes more intense. A similar
      phenomenon is observed when these organs are exposed to unilateral illumination,
      i.e. enhanced acid efflux occurs on the dark side of the organ prior to the
      initiation of phototropic curvature and the pattern of differential acid efflux
      intensifies as phototropic curvature develops. These observations indicate that
      differential acid efflux occurs in response to tropistic stimuli and that the
      acid efflux pattern may mediate the development of tropistic curvatures. 

PMID- 24302422
TI  - Effects of freezing on isolated plant mitochondria.
AB  - Mitochondria isolated from spinach leaves (Spinacia oleracea L.) and potato
      tubers (Solanum tuberosum L.) were partly injured when subjected to freezing for
      2 to 4 h at-25 degrees C in salt solutions in the absence of cryoprotectants.
      Damage was manifested by the inactivation of respiratory properties and increase
      in the permeability of the mitochondrial membranes. Decrease in respiratory
      control indicated that the control mechanism of the electron transport chain was
      influenced by freezing. Oxidative phosphorylation was only slightly more affected
      than electron transport. The inactivation of the membrane systems was caused by
      an increase in the concentration of membrane-toxic solutes. This was confirmed by
      treatment of the organelles at 0 degrees C in solutions of high salt
      concentrations. When sugar was present in the course of freezing, mitochondria
      were partly or completely protected. On a molar basis, sucrose was more effective
      in membrane protection than glucose. Under certain conditions amino acids, e.g.,
      proline and hydroxyproline, also stabilized isolated mitochondria during
      freezing. 

PMID- 24302423
TI  - Metabolism of 2,4-dichlorophenoxyacetic acid in cell suspension cultures of
      soybean (Glycine max L.) and wheat (Triticum aestivum L.) : I. General results.
AB  - The metabolism of [2-(14)C]- and [ring-U-(14)C]2,4-dichlorophenoxyacetic acid
      (2,4-D) has been studied in cell suspension cultures of soybean (Glycine max L.)
      and wheat (Triticum aestivum L.). 2,4-D was extensively metabolized by both
      cultures, the rates of metabolism and the metabolite patterns remaining constant
      over at least 60 (soybean) and 25 (wheat) growth cycles. Amino acid conjugates
      were the predominant metabolite fraction in soybean cells whereas beta-D
      glucoside conjugates predominated in wheat cells. The two cell types studied also
      differed in the amino acid compositions of the amino acid conjugate fractions and
      in the aglycone patterns of the beta-D-glucoside fractions. Novel metabolite
      fractions of both wheat and soybean cells included a polar water-soluble
      metabolite fraction and a covalently modified protein fraction of low molecular
      weight. 

PMID- 24302424
TI  - Metabolism of 2,4-dichlorophenoxyacetic acid in cell suspension cultures of
      soybean (Glycine max L.) and wheat (Triticum aestivum L.) : II. Evidence for
      incorporation into lignin.
AB  - Cell suspension cultures of soybean (Glycine max L.) and wheat (Triticum aestivum
      L.) incorporated 2,4-dichlorophenoxyacetic acid (2,4-D) into a metabolite
      fraction which was insoluble in ethanol, water, and hot sodium dodecylsulphate.
      Further treatment with hot dimethylformamide solubilized a material which by the
      following criteria appeared to consist of 2,4-D derivatives covalently bound to
      lignin: i) co-chromatography of radioactivity and of UV-absorbing material upon
      gel permeation chromatography; ii) spectral similarity with authentic lignins (IR
      and UV-spectra, phloroglucinol reaction), 2,4-D appeared to be incorporated as
      the intact molecule, as shown by comparison of ring- and sidechain-labeled 2,4-D
      and by detection of monohydroxylated and intact 2,4-D as the major radioactive
      products of acid hydrolysis. The same compounds were released from the metabolite
      material which could not be solubilized in dimethylformamide. The incorporation
      of xenobiotics or their metabolites into lignin, followed by deposition in the
      cell wall, is suggested as a general pathway for 'local excretion' and
      detoxification by plant cells. 

PMID- 24302425
TI  - Fine structure of plant cuticles in relation to water permeability: The fine
      structure of the cuticle of Clivia miniata reg. leaves.
AB  - The fine structure of the upper cuticular membrane (CM) of Clivia miniata leaves
      was investigated using electron microscopy. The CM is made up of a thin (130 nm)
      lamellated cuticle proper (CP) and a thick (up to 7 MUm over periclinal walls)
      cuticular layer (CL) of marbled appearance. Evidence is presented to show that
      the electron lucent lamellae of the CP do not simply represent layers of soluble
      cuticular lipids (SCL). Instead, the lamellation is probably due to layers of
      cutin differing in polarity. It is argued that the SCL in the Cp are the main
      barrier to water. Thickening of the CM during leaf development takes place by
      interposition of cutin between the CM and the cellin wall. The cutin of young,
      expanding leaves has a high affinity for KMnO4 and is therefore relatively polar.
      As leaves mature, the external CL underneath the CP becomes non-polar, as only
      little contrast can be obtained with permanganate as the post fixative. 

PMID- 24302426
TI  - The role of endosymbiotic algae in photoaccumulation of green Paramecium
      bursaria.
AB  - The endosymbiotic unit of Paramecium bursaria with Chlorella sp. photoaccumulates
      in white, blue-green, and red light (lambda<700 nm), whereas alga-free Paramecia
      never do. The intensity of photoaccumulation depends on both the light fluence
      rate and the size of the symbiotic algal population. Photoaccumulation can be
      stopped completely with 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU), an
      inhibitor of photosynthetic electron transport. Hence the photosynthetic pigments
      of the algae act as receptors of the light stimulus for photomovement and a close
      connection must exist between photosynthesis of the algae and ciliary beating of
      the Paramecium. 

PMID- 24302427
TI  - Localization of membrane-associated calcium following cytokinin treatment in
      Funaria using chlorotetracycline.
AB  - We have investigated the changes in membrane-associated calcium that occur during
      cytokinin induced bud formation in Funaria hygrometrica Hedw. using the
      fluorescent Ca(2+)-chelate probe chlorotetracycline (CTC). In the target
      caulonema cells a localization of CTC fluorescent material becomes evident at the
      presumptive bud site 12 h after cytokinin treatment. By the time of the initial
      asymmetric division this region is four times as fluorescent as the entire
      caulonema cell. Bright CTC fluorescence remains localized in the dividing cells
      of the bud. To relate the changes in CTC fluorescence to changes in Ca(2+) as
      opposed to membrane-density changes we employed the general membrane marker N
      phenyl-1-naphthylamine (NPN). NPN fluorescence increases only 1.5 times in the
      initial bud cell. We conclude that the relative amount of Ca(2+) per quantity of
      membrane increases in this localized area and is maintained throughout bud
      formation. We suggest that these increases in membrane-associated Ca(2+) indicate
      a localized rise in intracellular free Ca(2+) concentration brought about by
      cytokinin action. 

PMID- 24302428
TI  - Degeneration of Trachymene pilosa exine by osmium tetroxide used in impregnation
      technique.
AB  - Mature pollen grains of Trachymene pilosa (Umbelliferae) were treated at 40
      degrees  C in 2% aqueous osmium for one to six days. Exine observed by (TEM) were
      progressively destroyed. After six days, they were reduced to a three-dimensional
      structure composed only of pollenkitt. 

PMID- 24302429
TI  - Specificity of a UDP-GalNAc pyranose-furanose mutase: a potential therapeutic
      target for Campylobacter jejuni infections.
AB  - Pyranose-furanose mutases are essential enzymes in the life cycle of a number of
      microorganisms, but are absent in mammalian systems, and hence represent novel
      targets for drug development. To date, all such mutases show preferential
      recognition of a single substrate (e.g., UDP-Gal). We report here the detailed
      structural characterization of the first bifunctional pyranose-furanose mutase,
      which recognizes both UDP-Gal and UDP-GalNAc. The enzyme under investigation
      (cjUNGM) is involved in the biosynthesis of capsular polysaccharides (CPSs) in
      Campylobacter jejuni 11168. These CPSs are known virulence factors that are
      required for adhesion and invasion of human epithelial cells. Using a combination
      of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference
      NMR spectroscopy, molecular dynamics and CORCEMA-ST calculations, we have
      characterized the binding of the enzyme to both UDP-Galp and UDP-GalpNAc, and
      compared these interactions with those of a homologous monofunctional mutase
      enzyme from E. coli (ecUGM). These studies reveal that two arginines in cjUNGM,
      Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme
      and in controlling its specificity to ultimately lead to a GalfNAc-containing
      CPS. In ecUGM, these arginines are replaced with histidine and lysine,
      respectively, and this results in an enzyme that is selective for UDP-Gal. We
      propose that these changes in amino acids allow C. jejuni 11168 to produce
      suitable quantities of the sugar nucleotide substrate required for the assembly
      of a CPS containing GalfNAc, which is essential for viability. 

PMID- 24302430
TI  - Controversies in prenatal diagnosis 3: should everyone undergoing invasive
      testing have a microarray?

PMID- 24302431
TI  - Job Stress in the United Kingdom: Are Small and Medium-Sized Enterprises and
      Large Enterprises Different?
AB  - This paper examines the relationships between firm size and employees' experience
      of work stress. We used a matched employer-employee dataset (Workplace Employment
      Relations Survey 2011) that comprises of 7182 employees from 1210 private
      organizations in the United Kingdom. Initially, we find that employees in small
      and medium-sized enterprises experience lower level of overall job stress than
      those in large enterprises, although the effect disappears when we control for
      individual and organizational characteristics in the model. We also find that
      quantitative work overload, job insecurity and poor promotion opportunities, good
      work relationships and poor communication are strongly associated with job stress
      in the small and medium-sized enterprises, whereas qualitative work overload,
      poor job autonomy and employee engagements are more related with larger
      enterprises. Hence, our estimates show that the association and magnitude of
      estimated effects differ significantly by enterprise size.

PMID- 24302432
TI  - A microfluidic reciprocating intracochlear drug delivery system with reservoir
      and active dose control.
AB  - Reciprocating microfluidic drug delivery, as compared to steady or pulsed
      infusion, has unique features which may be advantageous in many therapeutic
      applications. We have previously described a device, designed for wearable use in
      small animal models, that periodically infuses and then withdraws a sub
      microliter volume of drug solution to and from the endogenous fluid of the inner
      ear. This delivery approach results in zero net volume of liquid transfer while
      enabling mass transport of compounds to the cochlea by means of diffusion and
      mixing. We report here on an advanced wearable delivery system aimed at further
      miniaturization and complex dosing protocols. Enhancements to the system include
      the incorporation of a planar micropump to generate reciprocating flow and a
      novel drug reservoir that maintains zero net volume delivery and permits
      programmable modulation of the drug concentration in the infused bolus. The
      reciprocating pump is fabricated from laminated polymer films and employs a
      miniature electromagnetic actuator to meet the size and weight requirements of a
      head-mounted in vivo guinea pig testing system. The reservoir comprises a long
      microchannel in series with a micropump, connected in parallel with the
      reciprocating flow network. We characterized in vitro the response and
      repeatability of the planar pump and compared the results with a lumped element
      simulation. We also characterized the performance of the reservoir, including
      repeatability of dosing and range of dose modulation. Acute in vivo experiments
      were performed in which the reciprocating pump was used to deliver a test
      compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety
      and efficacy of the system. These advances are key steps toward realization of an
      implantable device for long-term therapeutic applications in humans. 

PMID- 24302433
TI  - 3T MRI and 128-slice dual-source CT cisternography images of the cranial nerves a
      brief pictorial review for clinicians.
AB  - There is a broad community of health sciences professionals interested in the
      anatomy of the cranial nerves (CNs): specialists in neurology, neurosurgery,
      radiology, otolaryngology, ophthalmology, maxillofacial surgery, radiation
      oncology, and emergency medicine, as well as other related fields. Advances in
      neuroimaging using high-resolution images from computed tomography (CT) and
      magnetic resonance (MR) have made highly-detailed visualization of brain
      structures possible, allowing normal findings to be routinely assessed and
      nervous system pathology to be detected. In this article we present an integrated
      perspective of the normal anatomy of the CNs established by radiologists and
      neurosurgeons in order to provide a practical imaging review, which combines 128
      slice dual-source multiplanar images from CT cisternography and 3T MR curved
      reconstructed images. The information about the CNs includes their origin, course
      (with emphasis on the cisternal segments and location of the orifices at the
      skull base transmitting them), function, and a brief listing of the most common
      pathologies affecting them. The scope of the article is clinical anatomy; readers
      will find specialized texts presenting detailed information about particular
      topics. Our aim in this article is to provide a helpful reference for
      understanding the complex anatomy of the cranial nerves.

PMID- 24302435
TI  - Some contemporary illusions.

PMID- 24302434
TI  - A tetradentate metalloligand: synthesis and coordination behaviour of a 2-pyridyl
      substituted cyclobutadiene iron complex.
AB  - The salt [K([18]crown-6){Cp*Fe(eta(4)-C4py4)}] (K1, py = 2-pyridyl, Cp* = C5Me5)
      is accessible by the reaction of an iron(0) naphthalene precursor and bis(2
      pyridyl)acetylene. Cyclic voltammetry and preparative investigations demonstrate
      the electron-rich nature of K1, which is reversibly oxidized to neutral
      [Cp*Fe(eta(4)-C4py4)] (1) at a low potential. The first coordination studies with
      iron(II) and zinc(II) chloride show that all four 2-pyridyl units may be employed
      for metal coordination.

PMID- 24302436
TI  - Religion, Type A behavior, and health.
AB  - In a study of air traffic controllers, religious differences are found in the way
      Type A behavior is associated with several health status indicators. Associations
      between the Jenkins Activity Survey (JAS) and physical illness incidence, health
      promotive behavior, diastolic and systolic blood pressure, subjective distress
      and impulse control problems, and alcohol consumption are examined by religious
      attendance, religious affiliation, and change in affiliation. Findings confirm
      that Type A does not vary significantly by religion. However, there are several
      significant findings between Type A and various health indicators. Type A is
      associated with illness incidence, overall and more strongly in several religion,
      subgroups. Type A and alcohol consumption are related positively in Protestants
      and converts, and negatively in churchgoing Catholics. Type A is related to
      impulse control problems in churchgoing Protestants and to subjective distress in
      churchgoing Catholics. Finally, in individuals with weak or no religious ties,
      Type A is associated with lower blood pressure. This last finding suggests that
      in some people (for example, the irreligious or unchurched), the coronary-prone
      behavior pattern may have cardiovascular effects which are salutary in at least
      one respect. 

PMID- 24302437
TI  - Issues of hope and faith in the cancer patient.
AB  - Akira Kurosawa's 1952 film about a man with a terminal gastric cancer introduces
      a discussion of hope and faith in the oncology patient. A psychodynamic
      relationship between hope and faith is explored, using Lawrence LeShan's research
      in cancer psychotherapy and Erik Erikson's lifespan developmental theory. LeShan
      describes a cancer personality characterized by hopeless despair, while Erikson
      formulates a psychogenetic framework for the development of hope and despair.
      Hope and faith are linked through the individual's earliest strivings toward
      basic trust in the world and his or her own self-efficacy. Accordingly, cancer
      psychotherapy may aim at restoring adult patients' faith in life and inner
      creative resources. 

PMID- 24302438
TI  - Solutions to neurosis: A theology of self.
AB  - For Karen Horney neurosis is a serious impediment to health and wholeness and has
      the power to place a person in bondage. Yet the situation is far from hopeless,
      for strivings and anxieties contain intrinsic value and can be directed
      positively to the purpose of human maturity. The theory lends itself to a strong
      theology of the self, and thus encourages the pastoral counselor who cooperates
      with the inherent strengths of the person in his or her drive toward health. 

PMID- 24302439
TI  - The capacity to forgive: An object relations perspective.
AB  - Forgiveness is commended by Christianity, as well as other religious traditions,
      as one of the most central of virtues, so central that the New Testament links
      man's very salvation to his ability to forgive. However, mental health
      professionals have correctly pointed out that the mandate to forgive is often
      used by religious patients in the service of defenses such as reaction formation,
      undoing, and denial. The forgiveness ideal is often misunderstood as a command
      not to experience aggressive feelings.It is the thesis of this paper that the
      capacity for genuine forgiveness is central not only to spiritual development but
      to psychological development as well. It is suggested that Kernberg's object
      relations theory provides the best model for understanding the nature and
      importance of forgiveness. Mature forgiveness does not involve the elimination of
      negative feelings toward others (or oneself) but the integration of negative and
      positive self-object representations and their connected affect. Anger at the
      offending persons must then be tempered by appreciation for their concomitant
      good qualities and motivations or, at the very least, empathy for the flaws which
      prompted them to behave destructively. The result is a more realistic and
      balanced view of others (and oneself), a more genuine relationship to the full
      range of one's own inner experience, and a greater ability to respond
      constructively to frustrating persons and situations. 

PMID- 24302440
TI  - Eleven interpretations of personal suffering.
AB  - Suffering is carefully defined in contrast to pain as the psychological
      experience being investigated. Under consideration, however, is only one's own
      suffering and not the suffering of other people. Interpretation is identified as
      the way of perceiving personal suffering. In a nine sentence paragraph the
      statements describe the perceptual, affective, and action-tending components of
      an attitude. The implications of assuming a particular attitude are brought to
      light in summary fashion in another paragraph. Eleven attitudes toward personal
      suffering are thus described and criticized. An attitude scale of 99 items is
      constructed from the descriptive statements of these 11 attitudes toward personal
      suffering. Plans for further research are indicated. 

PMID- 24302441
TI  - Ca(2+)/H (+) exchange, lumenal Ca(2+) release and Ca (2+)/ATP coupling ratios in
      the sarcoplasmic reticulum ATPase.
AB  - The Ca(2+) transport ATPase (SERCA) of sarcoplasmic reticulum (SR) plays an
      important role in muscle cytosolic signaling, as it stores Ca(2+) in
      intracellular membrane bound compartments, thereby lowering cytosolic Ca(2+) to
      induce relaxation. The stored Ca(2+) is in turn released upon membrane excitation
      to trigger muscle contraction. SERCA is activated by high affinity binding of
      cytosolic Ca(2+), whereupon ATP is utilized by formation of a phosphoenzyme
      intermediate, which undergoes protein conformational transitions yielding reduced
      affinity and vectorial translocation of bound Ca(2+). We review here biochemical
      and biophysical evidence demonstrating that release of bound Ca(2+) into the
      lumen of SR requires Ca(2+)/H(+) exchange at the low affinity Ca(2+) sites. Rise
      of lumenal Ca(2+) above its dissociation constant from low affinity sites, or
      reduction of the H(+) concentration by high pH, prevent Ca(2+)/H(+) exchange.
      Under these conditions Ca(2+) release into the lumen of SR is bypassed, and
      hydrolytic cleavage of phosphoenzyme may yield uncoupled ATPase cycles. We
      clarify how such Ca(2+)pump slippage does not occur within the time length of
      muscle twitches, but under special conditions and in special cells may contribute
      to thermogenesis. 

PMID- 24302442
TI  - Spatial separation of covalent, ionic, and metallic interactions in Mg11Rh18B8
      and Mg3Rh5B3.
AB  - The crystal structures of Mg11Rh18B8 and Mg3Rh5B3 have been investigated by using
      single-crystal X-ray diffraction. Mg11Rh18B8: space group P4/mbm; a=17.9949(7),
      c=2.9271(1) A; Z=2. Mg3Rh5B3: space group Pmma; a=8.450(2), b=2.8644(6),
      c=11.602(2) A; Z=2. Both crystal structures are characterized by trigonal
      prismatic coordination of the boron atoms by rhodium atoms. The [BRh6] trigonal
      prisms form arrangements with different connectivity patterns. Analysis of the
      chemical bonding by means of the electron-localizability/electron-density
      approach reveals covalent BRh interactions in these arrangements and the
      formation of B-Rh polyanions. The magnesium atoms that are located inside the
      polyanions interact ionically with their environment, whereas, in the structure
      parts, which are mainly formed by Mg and Rh atoms, multicenter (metallic)
      interactions are observed. Diamagnetic behavior and metallic electron transport
      of the Mg11Rh18B8 and Mg3Rh5B3 phases are in agreement with the bonding picture
      and the band structure.

PMID- 24302443
TI  - Differentiation of human induced pluripotent stem cells into brown and white
      adipocytes: role of Pax3.
AB  - Identification of molecular mechanisms involved in generation of different types
      of adipocytes is progressing substantially in mice. However, much less is known
      regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs)
      in humans, highlighting the need for an in vitro model of human adipocyte
      development. Here, we report a procedure to selectively derive BAP and WAPs from
      human-induced pluripotent stem cells. Molecular characterization of APs of both
      phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically
      expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We
      focused on Pax3 and we showed that expression of this transcription factor was
      enriched in human perirenal white adipose tissue samples expressing UCP1 and in
      human classical brown fat. Finally, functional experiments indicated that Pax3
      was a critical player of human AP fate as its ectopic expression led to convert
      WAPs into brown-like APs. Together, these data support a model in which Pax3 is a
      new marker of human BAPs and a molecular mediator of their fate. The findings of
      this study could lead to new anti-obesity therapies based on the recruitment of
      APs and constitute a platform for investigating in vitro the developmental
      origins of human white and brown adipocytes.

PMID- 24302444
TI  - The first synthesis of (-)-isoambreinolide, (+)-vitexifolin D and (+)-vitedoin B.
AB  - A very efficient method for synthesizing spirolactones is reported. Treatment of
      delta,epsilon-unsaturated carboxylic acids with iodine and triphenylphosphine
      under mild conditions leads to the corresponding spiro gamma-lactones in high
      yield and with complete stereoselectivity. Utilizing this, the first synthesis of
      the terpene spirolactones (-)-isoambreinolide, (+)-vitexifolin D and (+)-vitedoin
      B has been achieved. 

PMID- 24302445
TI  - Elongation of discotic liquid crystal strands and lubricant effects.
AB  - After a short review on the physics of pulled threads and their mechanical
      properties, the paper reports and discusses the strand elongation of disordered
      columnar phases, hexagonal or lamella-columnar, of small molecules or polymers.
      The mechanical properties appear to be relevant to the length of the columns of
      molecules compared to the thread length, instead of the usual correlation length.
      If, taking the entanglement effect into account, the column length is short, the
      strand exhibits rather fluid-like properties that may even look nematic-like at
      the macroscopic scale. The Plateau-Rayleigh instability breaks the thread shortly
      thereafter. However, because the hydrodynamic objects are the columns instead of
      the molecules, the viscosity is anomalously large. The observations show that the
      strands in the columnar phases are made of filaments, or fibrils, which are
      bundles of columns of molecules. This explains the grooves and rings, which are
      observed on the antenna or bamboo-like strand profiles. On pulling a strand, the
      elongation stress eventually exceeds the plasticity threshold, thus breaking the
      columns and the filaments. As a result, cracks, more exactly, giant dislocations
      are formed. These change the strand thickness by steps of different birefringence
      colors. Interestingly, the addition of a solute may drastically change the
      effective viscosity of the columnar phase and its mechanical properties. Some
      solutes, such as alkanes, exhibit lubricant and detangling properties, whereas
      others such as triphenylene, are antilubricant. 

PMID- 24302447
TI  - Two organic-inorganic hybrid 3D {P(5)W(30)}-based heteropolyoxotungstates with
      transition-metal/Ln-carboxylate-Ln connectors.
AB  - Two unique organic-inorganic hybrid polyoxometalates constructed from Preyssler
      type [Na(H2 O)P5 W30 O110 ](14-) ({P5 W30 }) subunits and TM/Ln-carboxylate-Ln
      connectors (TM=transition metal, Ln=lanthanide), KNa7 [{Sm6 Mn(MU-H2 O)2 (OCH2
      COO)7 (H2 O)18 }{Na(H2 O)P5 W30 O110 }]?22 H2 O (1) and K4 [{Sm4 Cu2 (gly)2
      (ox)(H2 O)24 }{NaP5 W30 O110 }]Cl2 ?25 H2 O (2; gly=glycine, ox=oxalate) have
      been hydrothermally synthesized and characterized by elemental analyses, IR
      spectra, UV/Vis-NIR spectra, thermogravimetric analyses, power X-ray diffraction,
      and single-crystal X-ray diffraction. Compound 1 displays one interesting 3D
      framework built by three types of subunits, {P5 W30 }, [Sm2 Mn(MU-H2 O)2 (OCH2
      COO)2 (H2 O)5 ](4+) , and [Sm4 (OCH2 COO)5 (H2 O)13 ](2+) , whereas 2 also
      manifests the other intriguing 3D architecture created by three types of
      subunits, {P5 W30 }, [SmCu(gly)(H2 O)8 ](4+) , and [Sm2 (ox)(H2 O)8 ](4+) . To
      our knowledge, 1 and 2 are the first 3D frameworks that contain {P5 W30 } units
      and TM/Ln-carboxylate-Ln connectors. The fluorescent properties of 1 and 2 have
      been investigated. 

PMID- 24302446
TI  - Transcriptomic responses provide a new mechanistic basis for the chemopreventive
      effects of folic acid and tributyrin in rat liver carcinogenesis.
AB  - The steady increase in the incidence and mortality of hepatocellular carcinoma
      (HCC) signifies a crucial need to understand better its pathogenesis to improve
      clinical management and prevention of the disease. The aim of this study was to
      investigate molecular mechanisms for the chemopreventive effects of folic acid
      and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar
      rats were subjected to a classic "resistant hepatocyte" model of liver
      carcinogenesis and treated with folic acid and tributyrin alone or in combination
      for 5 weeks during promotion stage. Treatment with folic acid and tributyrin
      alone or in combination strongly inhibited the development of glutathione-S
      transferase placental form (GSTP)-positive foci. Microarray analysis showed
      significant changes in gene expression. A total of 498, 655 and 940 of
      differentially expressed genes, involved in cell cycle, p53-signaling,
      angiogenesis and Wnt pathways, was identified in the livers of rats treated with
      folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these
      differentially expressed genes revealed that treatments inhibited angiogenesis in
      the preneoplastic livers. This was evidenced by the fact that 30 out of 77
      differentially expressed genes common to all three treatments are involved in the
      regulation of the angiogenesis pathway. The inhibition of angiogenesis was
      confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing
      activity of folic acid and tributyrin is associated with inhibition of
      angiogenesis at early stages of rat liver carcinogenesis. Importantly, the
      combination of folic acid and tributyrin has stronger chemopreventive effect than
      each of the compounds alone. 

PMID- 24302448
TI  - Wide brick tunnel randomization - an unequal allocation procedure that limits the
      imbalance in treatment totals.
AB  - In open-label studies, partial predictability of permuted block randomization
      provides potential for selection bias. To lessen the selection bias in two-arm
      studies with equal allocation, a number of allocation procedures that limit the
      imbalance in treatment totals at a pre-specified level but do not require the
      exact balance at the ends of the blocks were developed. In studies with unequal
      allocation, however, the task of designing a randomization procedure that sets a
      pre-specified limit on imbalance in group totals is not resolved. Existing
      allocation procedures either do not preserve the allocation ratio at every
      allocation or do not include all allocation sequences that comply with the pre
      specified imbalance threshold. Kuznetsova and Tymofyeyev described the brick
      tunnel randomization for studies with unequal allocation that preserves the
      allocation ratio at every step and, in the two-arm case, includes all sequences
      that satisfy the smallest possible imbalance threshold. This article introduces
      wide brick tunnel randomization for studies with unequal allocation that allows
      all allocation sequences with imbalance not exceeding any pre-specified threshold
      while preserving the allocation ratio at every step. In open-label studies,
      allowing a larger imbalance in treatment totals lowers selection bias because of
      the predictability of treatment assignments. The applications of the technique in
      two-arm and multi-arm open-label studies with unequal allocation are described.

PMID- 24302449
TI  - Changes in growth, appetite, food conversion efficiency and body composition in
      mice selected for high post-weaning weight gain on restricted feeding.
AB  - This study aimed to test the hypothesis that if animals were fed the same amount
      over the same time period, selection of the fastest growers would result in a
      change in the partitioning of metabolisable energy toward more protein and less
      fat deposition. Two mouse lines (S1 and S2) were selected for high 5 to 9 week
      weight gain corrected to mean 5 week weight. Appetite variation between mice was
      eliminated by feeding a fixed amount to each mouse daily. After 6 generations of
      selection, the lines were compared with an unselected control (C) on restricted
      and ad libitum levels of feeding for growth rate, appetite, food conversion
      efficiency and chemical body composition.Realised heritabilities of 5 to 9 week
      gain were 0.36+ 0.05 and 0.19+/-0.04 for S1 and S2 respectively. Nine week
      weights were increased by an average of 13% on both feeding levels. Most of this
      increase, particularly in S2, occurred before 5 weeks and was therefore outside
      the period of measurement used in selection. On ad libitum feeding, selection
      increased food intake per unit time by 6% but there was no increase per unit body
      weight. Food conversion efficiency (gain/food) increased by 12%. Compared with
      controls at 9 weeks, 3% more of the body weights of selected mice was fat and 1%
      less was protein. These differences were reduced but were still in the same
      direction when comparisons were made at the same body weight. Thus the expected
      change in energy partitioning toward greater protein and less fat deposition in
      the S lines did not occur.It was concluded that the increased growth and energy
      retention in the S lines was brought about by a reduction in maintenance
      requirement. To achieve the desired change in energy partitioning using a similar
      selection scheme, higher levels of dietary protein should be fed, and some
      measure of protein deposition rather than growth rate used as the selection
      criterion. 

PMID- 24302450
TI  - Induction of haploid and diploid plants though in vitro anther culture of haploid
      wheat (n=3x=21).
AB  - Five haploid plants of wheat were used for anther culture. Embryos were formed
      and six plants were regenerated. Of these, two were haploid (n=3x=21) and two
      diploid (2n=6x=42). The two diploids derived from the anthers of the same haploid
      wheat plant gave seeds, but the fertility was reduced in one of them showing,
      abnormalities at meiosis. 

PMID- 24302451
TI  - Meiosis and fertility of interspecific hybrids between Phaseolus vulgaris L. and
      P. acutifolius A. Gray.
AB  - Meiosis and fertility of interspecific hybrids obtained from reciprocal crosses
      between Phaseolus vulgaris and P. acutifolius were examined. Bivalents as well as
      univalents were found at Metaphase I. The majority of the microsporocytes had
      four or more univalents and the average was 6.3 univalents per cell. The average
      number of lagging chromosomes at Anaphase I was 2.3 per cell and the most
      frequent chromosome distribution at late Anaphase I was 10-12. The lower than
      expected number of lagging chromosomes as compared with the number of univalents
      at Metaphase I suggests the possible occurrence of precocious separation of
      bivalents. The male fertility as measured by pollen stainability was 17%,
      however, the frequency of pollen germination in selfing was 3.5%. Upon selfing of
      the interspecific hybrids, no dividing embryos were found even though 7 and 26%
      of the ovules were fertilized at 12 hours and four days after pollination. In
      backcrosses to P. vulgaris (male), 6 and 20% of the ovules were fertilized and 0
      and 4% of the ovules contained dividing embryos at the same sampling times. When
      P. acutifolius was the male parent, respective values were 8 and 31% for
      fertilization and 0 and 13% for ovules with dividing embryos. The frequencies of
      backcross embryos recovered at 14-26 days were in agreement with the frequencies
      of dividing embryos at four days. The ability to obtain backcross plantlets
      demonstrates the feasibility to further utilize interspecific hybrids for the
      improvement of P. vulgaris. 

PMID- 24302452
TI  - Theoretical basis of the plant domestication.
AB  - Plant domestication is stimulated by economic demands. Crop plant formation is
      controlled primarily by natural selection in cultivation; artificial selection is
      only a useful addition. The ecotypical nature of the initial material has great
      bearing on the success of domestication. The weeds of a convergent group were
      well adapted to being cultivated; weeds of a divergent group can be domesticated
      only with difficulty. Wild plants in nature are extremely varied ecotypically:
      some can be domesticated easily, others with difficulty. Some wild plants and
      weeds can be cultivated without genetic change (naturalization), while a genetic
      transmutation is necessary for the domestication of others (acclimatization). New
      domesticated ecotypes can be produced: 1. as a result of reconstruction of the
      initial populations and new ecotype synthesis on the basis of individual
      genotypes; 2. by means of hybridization of wild or weed initial genotypes with
      cultivated ones; 3. by use of new mutations in cultivation and further plant
      breeding. 

PMID- 24302453
TI  - C-banding in 6x-Triticale x Secale cereale L. hybrid cytogenetics.
AB  - The meiotic behaviour of F1 hybrids of hexaploid Triticale that differed in their
      genotypic or chromosomic constitution, and diploid rye, was investigated. Meiotic
      analysis were done by Feulgen and C-banding staining methods. A differential
      desynaptic effect in the hybrids was detected and explained in terms of genetic
      differences in pairing regulators. The high homoeologous pairing (A-B wheat
      chromosomes and wheat-rye chromosomes) observed in the hybrids can be explained
      in terms of an inhibition of the effect of a single dose of the Ph allele of the
      5B chromosome produced by two doses of the 5R chromosome. The higher homoeologous
      pairing detected in the hybrid 188 x 'Canaleja' could be the overall result of
      the balance between the Ph diploidizing system (1 dose), the pairing promoter of
      the 5R chromosome (2 doses) and that of the 3D chromosome (1 dose coming from the
      parental line Triticale with the substitution 3R by 3D). 

PMID- 24302454
TI  - A general approach to the concept of varietal ability for synthetic varieties.
AB  - Genetic effects for varietal value are defined at the level of the population of
      k-parent synthetic varieties. A simple expression for the total variance among
      synthetics arises directly from these definitions. A general expression for the
      covariance among related synthetics is given. Genetic effects are also defined in
      a completely general way so as to allow for any system of testing and used to
      derive an expression for the genetic advance in recurrent selection for varietal
      value. Covariances between relatives evaluated in the system of testing and in
      varietal combination are introduced, allowing a direct expression of the genetic
      advance in varietal development when parents are selected either individually or
      in groups. Some general implications for plant breeding are outlined. 

PMID- 24302455
TI  - Cytogenetic analysis of plants regenerated from colchicine-treated callus
      cultures of an interspecific Hordeum hybrid.
AB  - Hybrids of Hordeum vulgare (HV) x H. jubatum (HJ) were synthesized for purposes
      of introgressive breeding, but were sterile and the recovery of pure diploid
      tillers by colchicine applications in vivo was difficult. Plant regeneration from
      colchicine-treated callus cultures of the hybrid (HV x HJ) was investigated as a
      means to produce high numbers of pure diploid, fertile intermediates. 10 of 50
      plants regenerated in this manner exhibited variable chromosome numbers with
      means of approximately 37 (expected diploid number = 42). Cytological
      examinations of microsporogenesis in all such plants revealed a high incidence of
      bivalent formation at metaphase I (as compared to nearly complete asynapsis in
      the F1), but spindle and chromosome abnormalities in later meiotic stages led to
      complete sterility. Approximately 40% of HJ plants regenerated from colchicine
      treated calli appeared to be pure tetraploids of high fertility. These techniques
      are hence useful for high frequency production of diploid or polyploid plants. 

PMID- 24302456
TI  - Hypoxia-independent gene expression mediated by SOX9 promotes aggressive
      pancreatic tumor biology.
AB  - Pancreatic cancer aggressiveness is characterized by its high capacity for local
      invasion, ability to promote angiogenesis, and potential to metastasize. Hypoxia
      is known to represent a crucial step in the development of aggressive malignant
      features of many human cancers. However, micrometastatic tumors are not typically
      subjected to hypoxic events during early stages of dissemination; therefore, it
      is unclear how these tumors are able to maintain their aggressive phenotype.
      Thus, the identification of regulators of hypoxia-related genes in
      aggressive/metastatic tumors represents a fundamental step for the design of
      future therapies to treat pancreatic cancer. To this end, transcriptomic profiles
      were compared between the nonmetastatic pancreatic cancer cell line FG (LMET) and
      its angiogenic/metastatic derivate L3.6pl (HMET) under normoxic or hypoxic
      conditions. Cluster analysis revealed a number of transcripts that were induced
      by hypoxia in nonmetastatic cancer cells. Strikingly, this cluster was determined
      to be constitutively activated under normoxia in the metastatic cancer cells and
      could not be further induced by hypoxia. A subset of these transcripts were
      regulated by the transcription factor SOX9 in the aggressive-metastatic cells,
      but driven by hypoxia-inducible factor-1alpha (HIF-1alpha) in the parental
      nonmetastatic cell line. Moreover, these transcripts were enriched in cancer
      related networks including: WNT, CXCR4, retinoic acid, and (FAK) focal adhesion
      kinase, gene PTK2 signaling pathways. In functional assays, inhibition of SOX9
      expression in HMET cells led to increased apoptosis and reduced migration in
      vitro and a significant reduction in primary tumor growth, angiogenesis, and
      metastasis following orthotopic tumor cell injection. At the molecular level, the
      control of SOX9 expression was associated with changes in the methylation status
      of the SOX9 promoter. Finally, SOX9 upregulation was verified in a series of
      tumor specimens of patients with pancreatic carcinoma. IMPLICATIONS: SOX9
      represents a novel target for pancreatic cancer therapy.

PMID- 24302457
TI  - The assessment of breathlessness in pulmonary arterial hypertension: reliability
      and validity of the Dyspnoea-12.
AB  - Breathlessness is a cardinal symptom of pulmonary arterial hypertension (PAH);
      yet no breathlessness instrument has been previously tested for reliability and
      validity for this population. Using a cross-sectional design, we tested the
      psychometric properties of the Dyspnoea-12 (D-12), for the assessment of
      breathlessness in PAH. Pearson's correlations with World Health Organization
      functional class (WHO FC), Minnesota Living with Heart failure - pulmonary
      hypertension modified version (MLHF-PH), Hospital Anxiety and Depression scale
      (HADS) and 6-minute walk distance test (6MWD) were conducted. Participants (n =
      176) were mostly female (70.5%), mean age 54.3+/-14 years; diagnosed with
      idiopathic PAH (48.9%), congenital heart disease (27.8%) and connective tissue
      disease (23.3%); and most were WHO FC II (32.4%) and III (52.3%). The D-12 showed
      excellent internal consistency for the total and two-component scores for
      physical and emotional (Cronbach's alpha 0.95, 0.93 and 0.94, respectively). D-12
      total score was significantly associated with MLHF-PH (r = 0.70), HADS (anxiety r
      = 0.54 and depression r = 0.68), WHO FC (r = 0.49), and 6MWD (r = -0.26). In
      patients with PAH, the D-12 - a short patient reported measure of breathlessness
      severity that taps the physical and emotional components, is a reliable and valid
      instrument. 

PMID- 24302458
TI  - An examination of the phytotoxicity of the water shield,Brasenia schreberi.
AB  - Antialgal, antibacterial, and allelopathic properties of the submersed, aquatic,
      dicotyledonous water shield,Brasenia schreberi Gmelin (Cabombaceae), were
      examined. Extracts ofB. schreberi were found to inhibit the eukaryotic
      alga,Chlorella pyrenoidosa, and the prokaryotic alga,Anabena flosaqua, as well as
      nine different bacteria. Lettuce seedling bioassay showedB. schreberi to be
      allelopathic. These phytotoxic properties probably contribute to the observed
      dominance ofB. schreberi in aquatic environments and also make it a promising
      candidate for allelopathic plant management of aquatic weeds. 

PMID- 24302459
TI  - Variations in mouse (Mus musculus) urinary volatiles during different periods of
      pregnancy and lactation.
AB  - Mouse urine samples from different pregnancy and lactation periods were examined
      by capillary gas chromatography to assess variations in the volatile signals that
      may affect the endocrine function of other females. Statistically significant
      changes in the excretion of certain urinary volatiles were observed; from 26
      readily quantifiable constituents, 14 appear to be under the endocrine control.
      These selected components, positively identified through mass spectrometry and
      retention data, and the synthetic standards are ketones, unsaturated alcohols,
      esters, and cyclic vinyl ethers. 

PMID- 24302460
TI  - Responses of freshwater prawn,Macrobrachium rosenbergii, to chemical attractants.
AB  - Chemoreception in the adults of the freshwater prawnMacrobrachium rosenbergii was
      investigated under controlled laboratory conditions, using behavioral assays.
      Tests were carried out on groups, as well as on individuals, all at their
      intermolt stages of the molt cycle, and prestarved for three to four days. Of 28
      different substances tested, the amino acids taurine, glycine, arginine, and
      betaine, as well as trimethylamine, elicited a positive behavioral response in at
      least 50% of the test animals when applied at a threshold concentration of 10(-5)
      10(-8) M. A positive response comprises enhanced antennular flicking and food
      search motion. Of the various nucleotides tested for chemoattraction, only
      adenosine monophosphate elicited a response similar to that of the above amino
      acids, although at a concentration of 10(-4) M, whereas adenosine diphosphate
      required a dosage of 10(-1) M. 

PMID- 24302461
TI  - Behavioral evidence for multicomponent trail pheromone in the
      termite,Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae).
AB  - Evidence is presented for a multicomponent trail pheromone in the eastern
      subterranean termiteReticulitermes flavipes (Kollar). Choice tests were used to
      compare strength and persistency of trails made by termites in glass tubes. Tubes
      connected to termite nests for 24 hr were marked by termites with an extremely
      long-lasting chemical that persisted for at least one year, and a highly volatile
      substance that decayed in 15 min. Individual termites varied the trail they
      deposited under different circumstances. When removed from the nest and placed in
      a clean tube, they deposited a highly volatile substance. They left stronger and
      more persistent trails when exploring clean tubes attached to the nest. When they
      discovered a new food source, they left trails that were more attractive and far
      more persistent than trails made by exploring or displaced termites. A food trail
      made by 15 workers was still effective after 24 hr, whereas a trail made by 50
      displaced workers, walking one after another through a tube, lasted only 5 min. 

PMID- 24302462
TI  - Isolation, identification, and synthesis of male-produced sex pheromone of papaya
      fruit fly,Toxotrypana curvicauda Gerstaecker (Diptera: Tephritidae).
AB  - A male-produced sex pheromone of the papaya fruit fly,Toxotrypana curvicauda
      Gerstaecker, was isolated from volatiles collected from air passed over calling
      males and was identified as 2-methyl-6-vinylpyrazine by comparative gas-liquid
      chromatographic and spectroscopic evidence. Synthetic 2-methyl-6-vinylpyrazine
      elicited typical pheromonal responses from unmated mature female flies such as
      walking, running, and flying in an arena bioassay; flying upwind with a zigzag
      flight pattern; and hovering in the pheromone plume in a wind-tunnel bioassay.
      These responses were similar quantitatively and qualitatively to responses to
      naturally occurring pheromone from calling male papaya fruit flies. 

PMID- 24302463
TI  - Anti-inflammatory effects of hydrophilic and lipophilic statins with hyaluronic
      acid against LPS-induced inflammation in porcine articular chondrocytes.
AB  - The objective of the study is to understand the therapeutic effects of lipophilic
      (simvastatin) and hydrophilic statins (pravastatin) combined with/without
      hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model
      of articular chondrocytes. HA in combination with different doses of simvastatin
      or pravastatin were used. Beside cytotoxicity, the influence of statins on NO
      production, pro-inflammatory cytokine, inflammatory mediators, and NF-kappaB p50
      protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand
      breakage. Two statins were less able to lower NF-kappaB activity when they were
      administrated along without HA. The gene expression demonstrates that simvastatin
      and pravastatin had the ability to decrease pro-inflammatory and inflammatory
      mediator levels. High dose simvastatin with or without HA down regulated
      inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms
      the regulatory effect of statins with or without HA over the apoptosis of
      chondrocytes, especially in hydrophilic statins. The significant down-regulation
      of inflammatory mediators suggests that intra-articular injection of HA in
      combination with statins might feasibly slow the progress of osteoarthritis.
      Administration of simvastatin or pravastatin with hyaluronic acid may produce
      beneficial effects for OA treatment, but with better results when hydrophilic
      statin was used.

PMID- 24302464
TI  - A unified approach to the daucane and sphenolobane bicyclo[5.3.0]decane core:
      enantioselective total syntheses of daucene, daucenal, epoxydaucenal B, and 14
      para-anisoyloxydauc-4,8-diene.
AB  - Access to the bicyclo[5.3.0]decane core found in the daucane and sphenolobane
      terpenoids via a key enone intermediate enables the enantioselective total
      syntheses of daucene, daucenal, epoxydaucenal B, and 14-para-anisoyloxydauc-4,8
      diene. Central aspects include a catalytic asymmetric alkylation followed by a
      ring contraction and ring-closing metathesis to generate the five- and seven
      membered rings, respectively. 

PMID- 24302465
TI  - Review of thoracic duct anatomical variations and clinical implications.
AB  - The thoracic duct (TD) transports ingested fat, drains lymph from the
      gastrointestinal vascular bed, and delivers the lymph to central veins in the
      neck. Preliminary evidence suggests that diversion of TD lymph may mitigate the
      severity of end-organ dysfunction in critical illness. Variations in the anatomy
      of the TD may determine whether reliable and safe cannulation of the duct, a
      necessary step for diversion, is possible. A systematic review was undertaken
      using the Google Scholar, MEDLINE, PubMed, and Scopus databases until 31st March,
      2013. Both English and non-English articles were searched for, and surgical,
      cadaveric, and radiologic studies were included. Fifty-seven articles from the
      past 102 years were retrieved. There are significant variations in the anatomy of
      the TD in terms of its formation at the cisterna chyli, its course through the
      thorax, and its termination in the venous system. The most common site of
      termination is at the internal jugular vein (46%), followed by the
      jugulosubclavian angle (32%), and the subclavian vein (18%). An improved
      understanding of the anatomy of the TD would help surgeons to avoid inadvertent
      injury and potentially afford new opportunities for diagnosis and intervention in
      patients with critical illness.

PMID- 24302466
TI  - Exercise programs for people with dementia.
AB  - BACKGROUND: This is an update of our previous 2008 review. Several recent trials
      and systematic reviews of the impact of exercise on people with dementia are
      reporting promising findings.  OBJECTIVES: Primary: Do exercise programs for
      older people with dementia improve cognition, activities of daily living (ADLs),
      challenging behaviour, depression, and mortality in older people with
      dementia?Secondary: Do exercise programs for older people with dementia have an
      indirect impact on family caregivers' burden, quality of life, and mortality?Do
      exercise programs for older people with dementia reduce the use of healthcare
      services (e.g. visits to the emergency department) by participants and their
      family caregivers? SEARCH METHODS: We identified trials for inclusion in the
      review by searching ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia
      and Cognitive Improvement Group's Specialised Register, on 4 September 2011, and
      again on 13 August 2012. The search terms used were: 'physical activity' OR
      exercise OR cycling OR swim* OR gym* OR walk* OR danc* OR yoga OR 'tai chi'.
      SELECTION CRITERIA: In this review, we included randomized controlled trials in
      which older people, diagnosed with dementia, were allocated either to exercise
      programs or to control groups (usual care or social contact/activities) with the
      aim of improving cognition, ADLs, behaviour, depression, and mortality. Secondary
      outcomes related to the family caregiver(s) and included caregiver burden,
      quality of life, mortality, and use of healthcare services. DATA COLLECTION AND
      ANALYSIS: Independently, at least two authors assessed the retrieved articles for
      inclusion, assessed methodological quality, and extracted data. Data were
      analysed for summary effects using RevMan 5.1 software. We calculated mean
      differences or standardized mean difference (SMD) for continuous data, and
      synthesized data for each outcome using a fixed-effect model, unless there was
      substantial heterogeneity between studies, when we used a random-effects model.
      We planned to explore heterogeneity in relation to severity and type of dementia,
      and type, frequency, and duration of exercise program. We also evaluated adverse
      events. MAIN RESULTS: Sixteen trials with 937 participants met the inclusion
      criteria. However, the required data from three trials and some of the data from
      a fourth trial were not published and not made available. The included trials
      were highly heterogeneous in terms of subtype and severity of participants'
      dementia, and type, duration and frequency of exercise. Only two trials included
      participants living at home. Our meta-analysis suggested that exercise programs
      might have a significant impact on improving cognitive functioning (eight trials,
      329 participants; SMD 0.55, 95% confidence interval (CI) 0.02 to 1.09). However,
      there was substantial heterogeneity between trials (I(2) value 80%), most of
      which we were unable to explain. We repeated the analysis omitting one trial, an
      outlier, that included only participants with moderate or severe dementia. This
      reduced the heterogeneity somewhat (I(2) value 68%), and produced a result that
      was no longer significant (seven trials, 308 participants; SMD 0.31, 95% CI -0.11
      to  0.74). We found a significant effect of exercise programs on the ability of
      people with dementia to perform ADLs (six studies, 289 participants; SMD 0.68,
      95% CI 0.08 to 1.27). However, again we observed considerable unexplained
      statistical heterogeneity (I(2) value 77%) in this meta-analysis. This means that
      there is a need for caution in interpreting these findings. In further analyses,
      we found that the burden experienced by informal caregivers providing care in the
      home may be reduced when they supervise the participation of the family member
      with dementia in an exercise program (one study, 40 participants; MD -15.30, 95%
      CI -24.73 to -5.87), but we found no significant effect of exercise on
      challenging behaviours (one study, 110 participants; MD -0.60, 95% CI -4.22 to
      3.02), or depression (six studies, 341 participants; MD -0.14, 95% CI -0.36 to
      0.07) . We could not examine the remaining outcomes, quality of life, mortality,
      and healthcare costs, as either the appropriate data were not reported, or we did
      not retrieve trials that examined these outcomes. AUTHORS' CONCLUSIONS: There is
      promising evidence that exercise programs can have a significant impact in
      improving ability to perform ADLs and possibly in improving cognition in people
      with dementia, although some caution is advised in interpreting these findings.
      The programs revealed no significant effect on challenging behaviours or
      depression. There was little or no evidence regarding the remaining outcomes of
      interest.

PMID- 24302467
TI  - Oxygen levels in thermoplastic microfluidic devices during cell culture.
AB  - We developed a computational model to predict oxygen levels in microfluidic
      plastic devices during cell culture. This model is based on experimental
      evaluation of oxygen levels. Conditions are determined that provide adequate
      oxygen supply to two cell types, hepatocytes and endothelial cells, either by
      diffusion through the plastic device, or by supplying a low flow rate of medium. 

PMID- 24302468
TI  - Distributional reaction time properties in the Eriksen task: marked differences
      or hidden similarities with the Simon task?
AB  - In conflict tasks, the irrelevant stimulus attribute needs to be suppressed for
      the correct response to be produced. In the Simon task, earlier researchers have
      proposed that this suppression is the reason that, after an initial increase, the
      interference effect decreases for longer RTs, as reflected by late, negative
      going delta plots. This view has been challenged by observations of positive
      going delta plots, even for long RTs, in other conflict tasks, despite a similar
      necessity for suppression. For late negative-going delta plots to be interpreted
      as reflecting suppression, a necessary, although maybe not sufficient, condition
      is that similar patterns should be observed for other conflict tasks. We reasoned
      that a similar suppression could be present, but hidden, in the Eriksen flanker
      task. By recording and analyzing electromyograms of the muscles involved in
      response execution, we could compute delta plots separately for trials that
      elicited a subthreshold incorrect response activation (partial error). Late
      negative-going delta plots were observable on partial-error trials, although they
      were weaker than for the Simon task, reducing the impact of this inversion on the
      overall distribution. We further showed that this pattern is modulated by time
      pressure. Those results indicate that mechanisms leading to negative-going delta
      plots, similar to those observed in the Simon task, are also at play in the
      Eriksen task. The link between negative-going delta plots and executive online
      control is discussed. 

PMID- 24302469
TI  - Restoration of male fertileNicotiana by fusion of protoplasts derived from two
      different cytoplasmic male-sterile cybrids.
AB  - Using the 'donor-recipient' protoplast-fusion technique, we have recently
      constructed several alloplasmic-like lines ofNicotiana in which the original
      cytoplasms (or part of them) of eitherN. tabacum orN. sylvestris were replaced
      respectively, either byN. undulata or byN. bigelovii cytoplasms. These
      cybridizations resulted in two kinds of cytoplasmic male-sterile (CMS) cybrid
      plants:N. tabacum withN. undulata-like cytoplasm andN. sylvestris withN.
      bigelovii-like cytoplasm. Fusion of protoplasts, derived from the above two CMS
      types, by the 'donor-recipient' technique, lead to the recovery of 21 cybrid
      calli. One of these regenerated a cybrid with fertile pollen but having shortened
      filaments and slighly tappered anthers. Self pollination of the latter cybrid
      resulted in a second generation progeny having almost normal filaments and
      anthers. Further selfings produced a third generation in which numerous plants
      had normal stamens and fertile pollen. Mitochondrial DNA (mtDNA) analysis of
      second and third generation progenies revealed a novel pattern which differed
      from each of the parental CMS cybrids and also from the mtDNA of normal, male
      fertileNicotiana species. The results suggest that mtDNA recombination between
      different types of CMS can lead to restoration of male-fertility. 

PMID- 24302470
TI  - The region distal to the rRNA operon from chloroplasts of maize contains genes
      coding for tRNA(Arg)(ACG) and tRNA (Asn)(GUU).
AB  - The nucleotide sequence distal to the rRNA operon from maize chloroplasts has
      been analyzed. It contains genes coding for tRNA(Arg)(ACG) and tRNA(Asn)(GUU).
      The tRNA(Arg)(ACG) gene, which is separated from the last rRNA gene of the rRNA
      operon, the 5S rDNA, by an intergenic region of 252 bp, has the same orientation
      as the rRNA operon. By S1 and primer extension mapping, the existence of
      transcripts from the entire 5S rDNA/tDNA(Arg)(ACG) intergenic region can be
      demonstrated. It is, therefore, concluded that tRNA(Arg)(ACG) represents a
      trailer tRNA which is cotranscribed with 5S rRNA as part of the primary rRNA
      transcript. The tDNA(Asn)(GUU), which is separated from tDNA(Arg)(ACG) by an
      intergenic region of 253 bp, has the opposite orientation with respect to the
      rRNA operon; it, therefore, represents a separate transcriptional unit whose
      promoter remains to be located. It is proposed that the two tRNA genes possess a
      common terminator region, which functions in both directions of transcription. 

PMID- 24302471
TI  - Silene cDNA clones for a divergent chlorophyll-a/b-binding protein and a small
      subunit of ribulosebisphosphate carboxylase.
AB  - We have isolated and analyzed cDNA clones for aSilene pratensis chlorophyll-a/b
      binding protein (CAB) and a small subunit (SS) of ribulosebisphosphate
      carboxylase. These cDNA clones contain the coding information for the complete
      transit peptides. The CAB clone codes for a divergent CAB protein that differs
      from most published CAB sequences in both the transit peptide part and in the
      amino terminal part of the mature protein, a region with an important regulatory
      function. The SS clone codes for a precursor that is homologous to other
      published precursor sequences. In the mature part some non-conservative changes
      are observed.Silene cDNA clones for four chloroplast specific precursor proteins
      that are directed towards three different chloroplast compartments have been
      analyzed and the transit peptides compared. 

PMID- 24302472
TI  - A protein induced by NaCl in suspension cultures ofNicotiana tabacum accumulates
      in whole plant roots.
AB  - We have characterized a 26 000 dalton (26 000 D) protein which accumulates
      inNicotiana tabacum cuspension cells grown in media containing 10-25 g/l NaCl (7,
      11, 17). Antibody was prepared against this protein and used to examine protein
      accumulation in both suspension cells and whole plants. Western blot analysis
      revealed that the 26 000 D protein also accumulates in suspension cells grown in
      the absence of NaCl as they approach stationary phase but the accumulation never
      reaches the level seen in the salt adapted cells. This protein also accumulates
      after treatment with other agents which lower the water potential, such as PEG
      and KCl, but no increase is seen after nonosmotic stresses such as heat shock and
      growth in cadmium chloride. The 26 000 D protein is found not only in whole
      tobacco plants but also in other members of the Solanaceae that were tested, as
      well as in alfalfa and green beans. The accumulation of the protein seems to be
      tissue specific as there is considerably more accumulation in roots than in stems
      or leaves of greenhouse grown plants. We have been unable to correlate
      accumlation of the 26 000 D protein with salt in wild tomato species but have
      demonstrated an increase in the accumulation of this protein with salt stress in
      hydroponically grown tomato plants. These results lead to speculation as to the
      role of this protein in responding to lowered water potential in the whole plant.

PMID- 24302473
TI  - Two soybean ribulose-1,5-bisphosphate carboxylase small subunit genes share
      extensive homology even in distant flanking sequences.
AB  - Soybean contains a multigene family which encodes the small subunit of ribulose
      1,5-bisphosphate carboxylase (RuBPCss). A member of this gene family, SRS4, has
      been isolated from a soybean genomic DNA library. Its nucleotide sequence has
      been determined and compared to the sequence of SRS1, a previously characterized
      RuBPCss gene from soybean. Relevant regulatory sequences such as the PuPuCCAAT
      boxes, TATA box, the actual start of transcription and poly A addition sites are
      conserved between the two genes. Using a gene specific synthetic probe to the 3'
      flanking region the steady state mRNA levels of SRS4, like SRS1, are shown to be
      very high in light grown soybean seedlings and low in seedlings grown in
      darkness. SRS1 and SRS4 are very closely related, the three exons being 96%, 93%
      and 96.5% homologous in nucleotide sequence. The polypeptide sequences are nearly
      identical with only one amino acid change in each of the three exons encoding the
      178 amino acid precursor polypeptide. The two introns are about 75% homologous
      and the flanking regions are more than 85% homologous (700 base pairs on the 5'
      end and 300 base pairs on the 3' end). Furthermore, hybridization studies between
      lambda clones containing the SRS1 and SRS4 genes reveal that a region of strong
      homology extends at least 4 kb on the 5' end and about 1.1 kb on the 3' end. We
      propose that these two genes may be alloalleles or homeologous alleles. This
      proposal is consistent with soybean having an allotetraploid origin, and would
      imply that the divergence of two ancient Papilionoidae species gave rise to these
      two genes. 

PMID- 24302474
TI  - The complete deduced amino acid sequences of legumin beta-polypeptides from
      different genetic loci inPisum.
AB  - The deduced amino acid sequences of the beta-polypeptides ofPisum legumin from
      two loci on chromosome 1 were compared with one from a locus on chromosome 7. The
      chromosome 1-derived sequences were ~80% identical, but each was only ~50%
      homologous to the chromosome 7-derived sequence. Comparison of these sequences
      with those of homologous polypeptides from two other species of the Leguminoseae
      showed that the chromosome 1-derivedPisum sequences were more similar to legumin
      B than to legumin A fromVicia faba and were more closely related to group II than
      to group I glycinins fromGlycine max. The converse was true for the chromosome 7
      derivedPisum sequences. This suggests that divergence of legumin-like sequences
      predated speciation in these three members of the Leguminosease.Among the
      threePisum sequence classes, a highly variable region was identified within the
      alpha-polypeptide, just to the amino-terminal side of the alphabeta processing
      site. This region varied considerably in length within the three classes ofPisum
      alpha-polypeptide sequence, a variation which far exceeded that which has
      previously been described for other legumins and glycinins. The chromosome 7
      derived, and one of the chromosome 1-derived alpha-polypeptide sequences
      contained different tandem repeats in this region. 

PMID- 24302475
TI  - Developmental biochemistry of cottonseed embryogenesis and germination XVIII cDNA
      and amino acid sequences of members of the storage protein families.
AB  - We have sequenced cDNA clones representing each of the three distinct groups of
      storage proteins of the cotton seed. Characteristics of their mRNAs and derived
      proteins are given. Dot matrix analysis of the nucleotide and amino acid
      sequences shows that 2 of these groups of proteins have a great deal of vestigial
      homology at low stringency and should be considered subfamilies of a single
      storage protein gene family. The remaining group is quite distinct and should be
      considered a separate multigene family. It also can be divived into 2 subfamilies
      based on the presence or absence of glycosyl residues and other sequence
      differences.These proteins are processed to smaller species during embryogenesis,
      and all of the mature storage proteins of cotton can be traced back to these 2
      gene families.In view of these relationships we propose that these 2 families be
      called the alpha and beta globulins of cotton storage proteins, each comprised of
      an A and B subfamily. 

PMID- 24302476
TI  - STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates
      mouse ESC fates.
AB  - STAT3 can be transcriptionally activated by phosphorylation of its tyrosine 705
      or serine 727 residue. In mouse embryonic stem cells (mESCs), leukemia inhibitory
      factor (LIF) signaling maintains pluripotency by inducing JAK-mediated
      phosphorylation of STAT3 Y705 (pY705). However, the function of phosphorylated
      S727 (pS727) in mESCs remains unclear. In this study, we examined the roles of
      STAT3 pY705 and pS727 in regulating mESC identities, using a small molecule-based
      system to post-translationally modulate the quantity of transgenic STAT3 in
      STAT3(-/-) mESCs. We demonstrated that pY705 is absolutely required for STAT3
      mediated mESC self-renewal, while pS727 is dispensable, serving only to promote
      proliferation and optimal pluripotency. S727 phosphorylation is regulated
      directly by fibroblast growth factor/Erk signaling and crucial in the transition
      of mESCs from pluripotency to neuronal commitment. Loss of S727 phosphorylation
      resulted in significantly reduced neuronal differentiation potential, which could
      be recovered by a S727 phosphorylation mimic. Moreover, loss of pS727 sufficed
      LIF to reprogram epiblast stem cells to naive pluripotency, suggesting a dynamic
      equilibrium of STAT3 pY705 and pS727 in the control of mESC fate.

PMID- 24302478
TI  - The lateral and axial localization uncertainty in super-resolution light
      microscopy.
AB  - A study of the uncertainty of localizing single-molecule emitters for super
      resolution light microscopy is presented. Maximum likelihood estimation (MLE) is
      found to be superior to least-squares fitting for low background levels, but the
      performance difference between the two methods decreases to a few percent for
      practical background levels. It is shown that the performance limit of MLE, the
      Cramer-Rao lower bound, is well described by a concise analytical formula with
      only spot width and signal and background photon count as input parameters. These
      predictions for the lateral localization uncertainty are compared with the
      localization error obtained from repeated localizations of the same single
      molecule emitter. Agreement within a few percent is found, thus verifying the
      validity of the fitting model and the concise analytical approximation. The
      analysis is extended by novel analytical results for the dependence of the axial
      localization uncertainty on background level for the astigmatic, bifocal, and
      double-helix methods. 

PMID- 24302477
TI  - Palmitoyl-protein thioesterase 1 (PPT1): an obesity-induced rat testicular marker
      of reduced fertility.
AB  - Male obesity may lead to declines in testosterone levels, reproductive hormonal
      profile, and semen quantity. To assess the effects of obesity on spermatogenesis,
      Sprague-Dawley rats fed a high-fat diet served as a model of induced obesity. The
      litter sizes for females mated to obese males were significantly lower as
      compared to females mated with normal-diet-fed controls. Their serum high-density
      lipoprotein, low-density lipoprotein, cholesterol, and estradiol levels increased
      in obese males, but testosterone and follicle-stimulating hormone levels
      decreased. Testicular morphology disruptions included Sertoli-cell atrophy,
      disrupted tight junctions, and mitochondrial degeneration in spermatogenic cells.
      To further investigate the molecular mechanisms leading to high-fat-diet-induced
      changes, we employed testicular proteomic analysis on rats fed both types of
      diet. Three spots were up-regulated in rats fed a high-fat diet whereas two
      others were downregulated. One of the upregulated spots was palmitoyl-protein
      thioesterase 1 (PPT1), a lipoprotein metabolizing related enzyme localized to
      Sertoli cells. In a Sertoli-cell line cultured in a high-fat supplemented medium,
      PPT1 abundance was accompanied by increases in the endocytic vesicle-associated
      protein, clathrin, and decreases in the tight junctional proteins, ZO-1 and
      occludin. In conclusion, declines in rat male fertility induced by a high-fat
      diet are associated with an altered testicular protein expression pattern as well
      as disruption of testicular Sertoli-cell and spermatogenic-cell morphology. PPT1
      expression may provide a testicular marker of reduced fertility in obese males,
      as increases in its expression may be detrimental to Sertoli-cell function during
      spermatogenesis.

PMID- 24302479
TI  - Firearms and suicide in US cities.
AB  - On an average day in the USA more than 100 Americans die by suicide-half use
      firearms. Suicide rates overall and by firearms are higher, on average, in states
      where household firearm ownership is more common. In general this means in states
      where a greater proportion of the population lives in rural areas. The current
      ecological study focuses on the relation between measures of household firearm
      prevalence and suicide mortality in urban areas (metropolitan statistical areas
      and divisions) using survey-based measures of firearm ownership. Suicide rates
      (1999-2010) for metropolitan statistical areas that are comprised of large US
      cities come from death certificate records; rates of household firearm ownership
      come from the 2002 and 2004 Behavioural Risk Factor Surveillance System. Higher
      rates of firearm ownership are strongly associated with higher rates of overall
      suicide and firearm suicide, but not with non-firearm suicide. Stratification by
      gender, age and race did not materially affect the association between firearms
      and suicide. This study provides evidence consistent with previous case-control
      work and extends evidence from previous state- and region-level ecological
      studies that firearms in the home impose suicide risk above and beyond baseline. 

PMID- 24302480
TI  - Rates of intentionally caused and road crash deaths of US citizens abroad.
AB  - CONTEXT: Currently, little is known about rates of death by cause and country
      among US travellers. Understanding the risk by cause and country is imperative to
      risk communication and the development of risk reduction strategies. METHODS:
      Publicly available data on non-natural deaths of US citizens abroad were gathered
      from January 2003 to December 2009 from the US Department of State's Department
      Bureau of Consular Affairs. Traveller information was gathered from the US
      Department of Commerce Office of Travel and Tourism for the same time period.
      Rates of death were calculated by dividing the number of non-natural deaths of US
      citizens abroad by the number of US outbound visits for each country. RESULTS: A
      total of 5417 non-natural death events were retrieved between 2003 and 2009 from
      the US State Department. Intentionally caused death rates ranged from 21.44 per 1
      000 000 visits in the Philippines to 0 per 1 000 000 visits in several countries;
      the majority of countries had fewer than five intentionally caused deaths per 1
      000 000 visits. Rates of road traffic crashes were higher than rates of
      intentionally caused deaths in almost every instance. Thailand had the highest
      rate of deaths due to road traffic crashes (16.49 per 1 000 000), followed by
      Vietnam, Morocco and South Africa (15.12 per 1 000 000, 11.96 per 1 000 000 and
      10.90 per 1 000 000, respectively). Motorcycle deaths account for most of the
      heightened risk observed in Thailand and Vietnam. CONCLUSIONS: The leading cause
      of non-natural deaths in US travellers abroad was road crashes, which exceeds
      intentional injury as the leading cause of non-natural deaths in almost every
      country where US citizens travel. Southeast Asia had the highest unintentional
      injury death rates for US citizens abroad due to the high rates of deaths from
      motorcycle crashes.

PMID- 24302481
TI  - Impact of albuminuria on early neurological deterioration and lesion volume
      expansion in lenticulostriate small infarcts.
AB  - BACKGROUND AND PURPOSE: Albuminuria, a marker of chronic kidney disease, is
      associated with an increased risk of incident stroke and unfavorable long-term
      outcomes. However, the association of albuminuria with short-term outcomes and
      change in infarct volume in patients with acute small subcortical infarction
      remains unknown. METHODS: We retrospectively reviewed 85 consecutive patients
      with acute small subcortical infarcts in the lenticulostriate artery territory
      who were admitted to our stroke center within 24 hours of symptom onset and
      underwent serial diffusion-weighted imaging (DWI). Albuminuria was determined
      based on the urinary albumin-to-creatinine ratio obtained from a first morning
      spot urine after admission. Infarct volume was measured on axial sections of the
      initial and follow-up DWI. Early neurological deterioration (END) was defined as
      an increase of >=2 points in the National Institutes of Health Stroke Scale score
      during the first 5 days after admission. RESULTS: Albuminuria (UACR >=30 mg/g
      creatinine) was observed in 14 of 18 patients with END (77.8%) and in 25 of 67
      patients without END (37.3%), P=0.002. Multivariate logistic regression analysis
      revealed that albuminuria was associated with END after adjustment for age, low
      estimated glomerular filtration rate (<60 mL/min per 1.73 m2), and infarct volume
      on initial DWI (odds ratio, 6.64; 95% confidence interval, 1.62-27.21; P=0.009).
      In addition, albuminuria was an independent predictor of increase in infarct
      volume using multivariate linear regression analysis (beta coefficient=0.217;
      P=0.038). CONCLUSIONS: Our findings suggest that albuminuria is associated with
      END and infarct volume expansion in patients with small subcortical infarcts in
      the lenticulostriate artery territory.

PMID- 24302482
TI  - Arterial spin labeling versus bolus-tracking perfusion in hyperacute stroke.
AB  - BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a perfusion magnetic
      resonance imaging (MRI) technique that does not require contrast administration
      and thus may be more practical in hyperacute stroke than susceptibility-weighted
      bolus-tracking perfusion-weighted imaging (PWI). However, a threshold for ASL
      measurement of the ischemic penumbra needs to be determined. METHODS: A total of
      58 patients with acute hemispheric ischemic stroke were imaged within 6 hours of
      symptom onset with MRI including ASL, diffusion-weighted MRI (DWI), and PWI,
      after perfusion computed tomography (CTP). Patients had repeat MRI at 24 hours.
      On repeat imaging, 32 patients did not reperfuse and were used to determine the
      penumbra threshold. A receiver-operating curve and a volumetric analysis were
      undertaken to identify the ASL-cerebral blood flow (CBF) threshold for the acute
      penumbra compared with the 24-hour DWI lesion in patients without reperfusion and
      with the acute PWI and CTP-Tmax thresholds. RESULTS: An ASL-CBF threshold of 40%
      showed the highest area under the curve (AUC) for detection of the acute
      penumbra, defined by 24-hour DWI in nonreperfused patients (AUC 0.76, 95%
      confidence interval, 0.63-0.85), and was also accurate compared with the acute
      PWI-Tmax+6 seconds penumbral threshold (AUC 0.79, 95% confidence interval, 73-84)
      and acute CTP-Tmax 5.5 seconds penumbral threshold (AUC 0.77, 95% confidence
      interval, 72-84). Using a perfusion-to-diffusion mismatch ratio of 1.8:1, an ASL
      CBF 40% mismatch compared with PWI-Tmax+ 6 seconds-DWI and CTP mismatch showed
      good sensitivity (0.81) and specificity (0.71). CONCLUSIONS: ASL-DWI mismatch
      shows potential to identify salvageable tissue in hyperacute stroke.

PMID- 24302483
TI  - Balloon guide catheter improves revascularization and clinical outcomes with the
      Solitaire device: analysis of the North American Solitaire Acute Stroke Registry.
AB  - BACKGROUND AND PURPOSE: Efficient and timely recanalization is an important goal
      in acute stroke endovascular therapy. Several studies demonstrated improved
      recanalization and clinical outcomes with the stent retriever devices compared
      with the Merci device. The goal of this study was to evaluate the role of the
      balloon guide catheter (BGC) and recanalization success in a substudy of the
      North American Solitaire Acute Stroke (NASA) registry. METHODS: The investigator
      initiated NASA registry recruited 24 clinical sites within North America to
      submit demographic, clinical, site-adjudicated angiographic, and clinical outcome
      data on consecutive patients treated with the Solitaire Flow Restoration device.
      BGC use was at the discretion of the treating physicians. RESULTS: There were 354
      patients included in the NASA registry. BGC data were reported in 338 of 354
      patients in this subanalysis, of which 149 (44%) had placement of a BGC. Mean age
      was 67.3+/-15.2 years, and median National Institutes of Health Stroke Scale
      score was 18. Patients with BGC had more hypertension (82.4% versus 72.5%;
      P=0.05), atrial fibrillation (50.3% versus 32.8%; P=0.001), and were more
      commonly administered tissue plasminogen activator (51.6% versus 38.8%; P=0.02)
      compared with patients without BGC. Time from symptom onset to groin puncture and
      number of passes were similar between the 2 groups. Procedure time was shorter in
      patients with BGC (120+/-28.5 versus 161+/-35.6 minutes; P=0.02), and less
      adjunctive therapy was used in patients with BGC (20% versus 28.6%; P=0.05).
      Thrombolysis in cerebral infarction 3 reperfusion scores were higher in patients
      with BGC (53.7% versus 32.5%; P<0.001). Distal emboli and emboli in new territory
      were similar between the 2 groups. Discharge National Institutes of Health Stroke
      Scale score (mean, 12+/-14.5 versus 17.5+/-16; P=0.002) and good clinical outcome
      at 3 months were superior in patients with BGC compared with patients without
      (51.6% versus 35.8%; P=0.02). Multivariate analysis demonstrated that the use of
      BGC was an independent predictor of good clinical outcome (odds ratio, 2.5; 95%
      confidence interval, 1.2-4.9). CONCLUSIONS: Use of a BGC with the Solitaire Flow
      Restoration device resulted in superior revascularization results, faster
      procedure times, decreased need for adjunctive therapy, and improved clinical
      outcome.

PMID- 24302484
TI  - Dynamic permeability and quantitative susceptibility: related imaging biomarkers
      in cerebral cavernous malformations.
AB  - BACKGROUND AND PURPOSE: Hyperpermeability and iron deposition are 2 central
      pathophysiological phenomena in human cerebral cavernous malformation (CCM)
      disease. Here, we used 2 novel MRI techniques to establish a relationship between
      these phenomena. METHODS: Subjects with CCM disease (4 sporadic and 17 familial)
      underwent MRI imaging using the dynamic contrast-enhanced quantitative perfusion
      and quantitative susceptibility mapping techniques that measure hemodynamic
      factors of vessel leak and iron deposition, respectively, previously demonstrated
      in CCM disease. Regions of interest encompassing the CCM lesions were analyzed
      using these techniques. RESULTS: Susceptibility measured by quantitative
      susceptibility mapping was positively correlated with permeability of lesions
      measured using dynamic contrast-enhanced quantitative perfusion (r=0.49;
      P<=0.0001). The correlation was not affected by factors, including lesion volume,
      contrast agent, and the use of statin medication. Susceptibility was correlated
      with lesional blood volume (r=0.4; P=0.0001) but not with lesional blood flow.
      CONCLUSIONS: The correlation between quantitative susceptibility mapping and
      dynamic contrast-enhanced quantitative perfusion suggests that the phenomena of
      permeability and iron deposition are related in CCM; hence, more leaky lesions
      also manifest a more cumulative iron burden. These techniques might be used as
      biomarkers to monitor the course of this disease and the effect of therapy.

PMID- 24302485
TI  - Ultrasonographic findings of gonarthritis caused by toothpick: a case report.
AB  - We report a rare case of a 5-year-old patient with a toothpick in the knee joint
      resulting in septic arthritis. The toothpick was detected in the joint by
      sonography and was confirmed at surgery. A wooden foreign body is an uncommon
      cause of arthritis. This case report is followed by a discussion of the value of
      sonography in the diagnosis of wooden foreign-body arthritis.

PMID- 24302486
TI  - Model-based dose finding under model uncertainty using general parametric models.
AB  - The statistical methodology for the design and analysis of clinical Phase II dose
      response studies, with related software implementation, is well developed for the
      case of a normally distributed, homoscedastic response considered for a single
      timepoint in parallel group study designs. In practice, however, binary, count,
      or time-to-event endpoints are encountered, typically measured repeatedly over
      time and sometimes in more complex settings like crossover study designs. In this
      paper, we develop an overarching methodology to perform efficient multiple
      comparisons and modeling for dose finding, under uncertainty about the dose
      response shape, using general parametric models. The framework described here is
      quite broad and can be utilized in situations involving for example generalized
      nonlinear models, linear and nonlinear mixed effects models, Cox proportional
      hazards models, with the main restriction being that a univariate dose-response
      relationship is modeled, that is, both dose and response correspond to univariate
      measurements. In addition to the core framework, we also develop a general
      purpose methodology to fit dose-response data in a computationally and
      statistically efficient way. Several examples illustrate the breadth of
      applicability of the results. For the analyses, we developed the R add-on package
      DoseFinding, which provides a convenient interface to the general approach
      adopted here.

PMID- 24302487
TI  - Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta
      analysis with implications for cancer control.
AB  - We conducted a random-effects meta-analysis of 50 publications assessing the
      relationship between oral/oropharyngeal cancer and chewing betel quid, with
      (BQ+T) or without added tobacco (BQ-T), a common practice in many parts of Asia
      and globally among Asian immigrants. Exposure-response, by daily amount and years
      of BQ chewed, was assessed using spline models. Attributable fractions (PAF%)
      were calculated to estimate the public health impact if BQ were no longer chewed.
      The meta-relative risk (mRR) for oral/oropharyngeal cancer in the Indian
      subcontinent was 2.56 (95%CI, 2.00-3.28; 15 studies) for BQ-T and 7.74 (95%CI,
      5.38-11.13; 31 studies) for BQ+T; in Taiwan, China, the mRR for BQ-T was 10.98
      (95%CI, 4.86-24.84; 13 studies). Restricting to studies that adjusted for tobacco
      and alcohol use had only a small effect on the risk estimates. For BQ+T in the
      Indian subcontinent, the mRR was much higher in women (mRR, 14.56; 95%CI, 7.63
      27.76) than in men. Exposure-response analyses showed that the risk of
      oral/oropharyngeal cancer increased with increasing daily amount and duration
      (years) of chewing BQ in India and Taiwan, China. Roughly half of oral cancers in
      these countries could be prevented if BQ were no longer chewed (PAF%=53.7% for BQ
      T in Taiwan, China; PAF%=49.5% for BQ+T in India). We demonstrate that betel quid
      chewing, with or without added tobacco, increases the risk of oral/oropharyngeal
      cancer in an exposure-dependent manner, independently of tobacco and alcohol use.
      Further work is needed to explain the higher risks associated with chewing BQ-T
      in Taiwan, China.

PMID- 24302488
TI  - A rapid, single leaf assay for detecting the presence of 'S'-male-sterile
      cytoplasm in maize.
AB  - A simple, rapid, and reproducible assay is described for determining
      unambiguously the presence of S-type cytoplasm in male-sterile and male-fertile
      (restored) maize lines. Because the assay requires only 0.5 g leaf segment per
      sample, it is a single plant assay and the plant is not destroyed. Plants at any
      developmental stage can be used. The assay involves a 30 sec homogenization, 20
      min centrifugation, one hour lysis, overnight agarose electrophoresis, 30 min gel
      staining, and photography of the gel to produce a result in much less than 24 hr.
      Many samples can be assayed simultaneously. The various assay methods available
      for classifying maize cytoplasms are compared and discussed. 

PMID- 24302489
TI  - Temporal heterogeneity of outcrossing rates in alpine ash (Eucalyptus
      delegatensis R.T. Bak.).
AB  - Three seed crops of a Eucalyptus delegatensis population were assayed for their
      allozyme genotype at three loci to determine estimates of mating system
      parameters. In the pollen the allelic frequencies at each of the three loci were
      similar to those in the parents and the progeny. Overall there was a significant
      amount of inbreeding (23%) in the population. The levels of outcrossing in each
      crop were significantly different from each other indicating apparent temporal
      variation in outcrossing rates. The outcrossing rate was greatest in the oldest
      crop (85%) and lowest in the most recent crop (66%). Mean heterozygosity in the
      progeny of all three crops was less than the heterozygosity in the parents
      indicating that selection favours heterozygotes during the life cycle. The
      implications of a 'balanced' mixed mating system for a eucalypt breeding program
      are discussed. 

PMID- 24302490
TI  - Condensed chromatin in diploid and allopolyploid microseris species with
      different genome size: a quantitative electron microscopic study.
AB  - The species-specific proportion of chromatin in the condensed state was estimated
      by quantitative electron microscopic morphometry of nuclear sections in 9 diploid
      and 5 allopolyploid species of Microseris (Asteraceae). A positive correlation
      between the genome size (haploid DNA content, or C value) and the percentage of
      chromatin in the condensed state (as visible in ultrathin sections) was found in
      diploids (r=0.89). Nuclei of allopolyploid (tetraploid) species exhibit condensed
      chromatin in a percentage which corresponds to the average of the values found in
      the parents. This suggests that each parental genome controls chromatin
      condensation at interphase independently within the nucleus, and that the degree
      of condensation is not directly determined by the nuclear DNA content per se.
      Genome size differences among Microseris species may depend preferentially, but
      not entirely, on DNA fractions located in, and perhaps being the cause of,
      condensed chromatin. 

PMID- 24302491
TI  - Long-term selection for a quantitative character in large replicate populations
      of Drosophila melanogaster : Part 4: Relaxed and reverse selection.
AB  - Reverse and relaxed selection were carried out in sublines which were derived
      from six replicate lines of Drosophila during 86-89 generations of selection for
      increased abdominal bristle number, and the reverse selection sublines were
      reciprocally crossed with selection lines of their origin.The results of serial
      relaxed selection initiated at different generations of selection confirm that
      the accelerated responses observed in the selection lines were largely due to
      deleterious genes, particularly lethals, with large effects on the selected
      character. The decline in mean bristle number under relaxed selection was not
      much different between crowded and uncrowded relaxed sublines.Reverse selection
      initiated at generation 57 was very effective, though it failed to bring the mean
      back to the base population level, and the genetic differences between replicate
      sublines (two from each of the six lines) indicate that low bristle number genes
      were probably rare in the selection lines. The genes which were still segregating
      after 57 generations of selection, on the average, did not show any directional
      dominance. The contribution of the X-chromosome to selection response was
      proportional to its chromosome length. 

PMID- 24302492
TI  - Do S allele-specific peroxidase isoenzymes exist in self-incompatible Nicotiana
      alata?
AB  - In order to test Pandey's hypothesis that peroxidase isoenzymes determine S-gene
      specificity in Nicotiana alata, peroxidase isoenzymes in styles and pollen from
      various plants of an inbred- and a cross progeny were compared by means of starch
      gel electrophoresis and electrofocusing.No relation between the S-genotype and
      the peroxidase isoenzyme patterns of pollen or of styles could be established.
      The differences between the isoenzyme patterns of different S-genotypes were
      ascribed to differences in the genetic background of various plants that had the
      same S-genotype. 

PMID- 24302493
TI  - Enzyme variability in populations of aphids.
AB  - From 1976 to 1978 nine aphid species were investigated electrophoretically. A low
      degree of polymorphism was found. Only 5 of the species were polymorphic, and
      only at most in 3 enzyme systems out of 19. 

PMID- 24302494
TI  - Genetic polymorphism and evolution in parthenogenetic animals : Part 9: Absence
      of variation within parthenogenetic aphid clones.
AB  - The enzyme gene variability within parthenogenetic clones of Acyrtosiphon pisum
      has been followed by gel electrophoresis. No variation was observed within any
      clone. One enzyme locus was found to vary between clones. No evidence was found
      to support gene recombination due to the alleged endomeiosis. This hypothesis is
      proven to be also theoretically untenable. The low average heterozygosity in
      aphids is explained as a result of directional selection operating upon the
      parthenogenetic aphid clones, as a consequence of which the heterozygosity is
      lowered. 

PMID- 24302495
TI  - Plant regeneration through somatic embryogenesis in root-derived callus of
      ginseng (Panax ginseng C. A. Meyer).
AB  - Callus culture was initiated from expiants of mature root tissues of ginseng
      (Panax ginseng C.A. Meyer) on MS medium enriched with 2,4-D. The ageing callus
      produced numerous embryoids in this medium. Reculture of these embryoids in media
      (1/2 MS or B5) supplemented with benzyladenine and gibberellic acid resulted in
      profuse plantlet regeneration. 

PMID- 24302496
TI  - Segregation frequencies of radiation-induced viable mutants in Arabidopsis
      thaliana (L.) Heynh.
AB  - The segregation of viable mutants derived from various fast neutron and X-ray
      treatments of Arabidopsis seeds was studied in the M2- and M3-generation. An
      equal segregation frequency in the M2- and M3-generation was observed. This
      indicated that the M2-lines, each of which descended from a single silique from
      the top of the main inflorescence of an M1-plant, originated from non-chimeric
      tissue. Furthermore, it was found that neither radiation type nor radiation dose
      affected the segregation frequency of the mutants. The average segregation
      frequency of the mutants was 21.5 per cent and significantly below the Mendelian
      expectation of 25 per cent. It was found that the mutant deficit was mainly due
      to reduced transmission of the mutant gene through the gametophyte. These
      findings are discussed with reference to the transformation of mutant frequency
      scores to mutation frequency per cell. 

PMID- 24302497
TI  - Imaging amide proton transfer and nuclear overhauser enhancement using chemical
      exchange rotation transfer (CERT).
AB  - PURPOSE: This study investigates amide proton transfer (APT) and nuclear
      overhauser enhancement (NOE) in phantoms and 9L tumors in rat brains at 9.4
      Tesla, using a recently developed method that can isolate different contributions
      to exchange. METHODS: Chemical exchange rotation transfer (CERT) was used to
      quantify APT and NOEs through subtraction of signals acquired at two irradiation
      flip angles, but with the same average irradiation power. RESULTS: CERT separates
      and quantifies specific APT and NOE signals without contamination from other
      proton pools, and thus overcomes a key shortcoming of conventional CEST asymmetry
      approaches. CERT thus has increased specificity, though at the cost of decreased
      signal strength. In vivo experiments show that the APT effect acquired with CERT
      in 9L rat tumors (3.1%) is relatively greater than that in normal tissue (2.5%),
      which is consistent with previous CEST asymmetry analysis. The NOE effect
      centered at -1.6 ppm shows substantial image contrast within the tumor and
      between the tumor and the surrounding tissue, while the NOE effect centered at 
      3.5 ppm shows little contrast. CONCLUSION: CERT provides an image contrast that
      is more specific to chemical exchange than conventional APT by means of
      asymmetric CEST Z-spectra analysis.

PMID- 24302499
TI  - Comparison of two phenotypically distinct lattice corneal dystrophies caused by
      mutations in the transforming growth factor beta induced (TGFBI) gene.
AB  - PURPOSE: In this study, we investigated whether the phenotypic difference
      observed between two lattice corneal dystrophy type 1 (LCD type 1) cases caused
      by either a single A546D substitution or an A546D/P551Q double substitution in
      TGFBIp (transforming growth factor beta induced protein) can be ascribed to (i) a
      difference in the proteomes of corneal amyloid deposits, (ii) altered proteolysis
      of TGFBIp, or (iii) structural changes of TGFBIp introduced by the P551Q amino
      acid substitution. EXPERIMENTAL DESIGN: Amyloid deposits were isolated from the
      corneas of two siblings with LCD type 1 resulting from A546D/P551Q mutations in
      the TGFBI gene using laser capture microdissection and subsequently analyzed by
      LC-MS/MS. Proteolytic processing of TGFBIp was addressed by counting peptide
      spectra. Lastly, to study the possible effect of the P551Q substitution,
      recombinant FAS1-4 domain variants were subjected to in vitro stability assays.
      RESULTS: The amyloid proteomes and TGFBIp processing of the two A546D/P551Q LCD
      type 1 cases were similar to each other as well as to the A546D amyloid proteome
      previously reported by us. The stability assays revealed a minor destabilization
      of the FAS1-4 domain upon the addition of the P551Q mutation, moreover, it
      resulted in different accessibility to tryptic cleavage sites between the A546D
      and A546D/P551Q mutant FAS1-4 domain variants. CONCLUSION AND CLINICAL RELEVANCE:
      The difference in A546D and A546D/P551Q LCD type 1 phenotypes cannot be ascribed
      to altered corneal amyloid composition or altered in vivo proteolytic processing
      of TGFBIp. Instead, a small difference in thermodynamic stability introduced by
      the P551Q mutation most likely causes structural changes of TGFBIp. The MS
      proteomics data have been deposited to the ProteomeXchange with identifier
      PXD000307 (http://proteomecentral.proteomexchange.org/dataset/PXD000307).

PMID- 24302500
TI  - The impact of chronic kidney disease and cardiovascular comorbidity on mortality
      in a multiethnic population: a retrospective cohort study.
AB  - OBJECTIVE: To assess the impact of chronic kidney disease (CKD) and
      cardiovascular comorbidity on mortality in a multiethnic primary care population.
      DESIGN: Retrospective cohort study. SETTING: Inner-city primary care trust in
      West Midlands, UK. PARTICIPANTS: Individuals aged 40 years and older, of South
      Asian, black or white ethnicity, registered with a general practice and with
      their kidney function checked within the last 12 months (n=31 254). OUTCOME
      MEASURE: All-cause mortality. RESULTS: Reduced estimated glomerular filtration
      rate, higher albuminuria, older age, white ethnicity (vs South Asian or black
      ethnicity) and increasing cardiovascular comorbidities were independent
      determinants of a higher mortality risk. In the multivariate model including
      comorbidities and kidney function, the HR for mortality for South Asians was
      0.697 (95% CI 0.56 to 0.868, p=0.001) and for blacks it was 0.533 (95% CI 0.403
      to 0.704, p<0.001) compared to whites. CONCLUSIONS: The HR for death is lower for
      South Asian and black individuals compared to white individuals. This is, in
      part, independent of age, gender, socioeconomic status, kidney function and
      comorbidities. Risk of death is higher in individuals with CKD and with a higher
      cumulative cardiovascular comorbidity.

PMID- 24302498
TI  - Discovery and development of small molecule SHIP phosphatase modulators.
AB  - Inositol phospholipids play an important role in the transfer of signaling
      information across the cell membrane in eukaryotes. These signals are often
      governed by the phosphorylation patterns on the inositols, which are mediated by
      a number of inositol kinases and phosphatases. The src homology 2 (SH2)
      containing inositol 5-phosphatase (SHIP) plays a central role in these processes,
      influencing signals delivered through the PI3K/Akt/mTOR pathway. SHIP modulation
      by small molecules has been implicated as a treatment in a number of human
      disease states, including cancer, inflammatory diseases, diabetes,
      atherosclerosis, and Alzheimer's disease. In addition, alteration of SHIP
      phosphatase activity may provide a means to facilitate bone marrow
      transplantation and increase blood cell production. This review discusses the
      cellular signaling pathways and protein-protein interactions that provide the
      molecular basis for targeting the SHIP enzyme in these disease states. In
      addition, a comprehensive survey of small molecule modulators of SHIP1 and SHIP2
      is provided, with a focus on the structure, potency, selectivity, and solubility
      properties of these compounds.

PMID- 24302501
TI  - Socioeconomic inequalities in youth smoking in Brazil.
AB  - OBJECTIVE: The contribution of smoking to socioeconomic inequalities in health is
      increasing worldwide, including in Brazil. Youth smoking may play an important
      role in the increasing social inequalities related to smoking. This study
      investigates social determinants of smoking among 15-year-old to 19-year-old
      individuals. DESIGN: Cross-sectional study. SETTING: The study uses data of 3536
      participants aged 15-19 years of age of the Global Adult Tobacco Survey (GATS)
      and the National Household Sample Survey (Pesquisa Nacional por Amostragem de
      Domicilio, PNAD) obtained from household interviews. Smoking was defined as
      currently smoking tobacco products, regardless of frequency. Household
      socioeconomic indicators included per capita income, the educational level and
      sex of the head of the household, the presence of smoking restrictions and the
      number of smokers (excluding adolescents). Adolescent social factors included
      years of delaying school and social status (full-time student, working, and
      neither working nor studying). The hierarchical logistic regression analysis
      considered the effect of the complex sampling design. RESULTS: From 3536
      participants, 6.2% were smokers (95% CI 5.4 to 7.1). More men than women had the
      habit of smoking (7.2%; 5.9 to 8.6 vs 3.6%; 2.7 to 4.6). The likelihood of
      smoking was significantly greater for men and older teens. There was an upward
      trend in the OR of smoking according to the number of smokers in the house.
      Adolescents living in households with no smoking restrictions had a greater
      likelihood of being smokers. OR of smoking rose as the number of years of
      delaying school increased, being about three times greater among adolescents who
      were working and five times greater among those who were neither studying nor
      working. CONCLUSIONS: Results demonstrate that socioeconomic inequality in
      smoking is established at younger ages and that school delay as well as school
      abandonment may contribute to increased smoking-related inequalities. Smoking
      restrictions at home were protective against adolescents becoming smokers. Living
      with other smokers was a strong predictor of adolescents becoming smokers.

PMID- 24302502
TI  - Rationale, design and baseline data of a mixed methods study examining the
      clinical impact of a brief transition programme for young people with juvenile
      idiopathic arthritis: the DON'T RETARD project.
AB  - OBJECTIVES: To describe (1) the content of a transition programme for young
      people with juvenile idiopathic arthritis (JIA) designed as a brief intervention,
      (2) the rationale and design of a mixed-methods study evaluating the clinical
      impact of this transition programme and (3) to provide baseline data of the
      intervention group. DESIGN: An 'embedded experimental' design is used for the
      evaluation of the transition programme. A 'one-group pretest-posttest, with a non
      equivalent posttest-only comparison group design' is used to quantitatively
      evaluate the impact of the transition programme, applying both longitudinal and
      comparative analyses. Subsequently, experiences of adolescents and their parents
      who participated in the experimental group will be analysed qualitatively using
      content analysis. SETTING: Participants in the intervention are recruited at a
      tertiary care centre in Belgium. The comparison group participants are recruited
      from one tertiary and three secondary care centres in Belgium. PARTICIPANTS: The
      intervention group consists of 33 young people (25 females; 8 males) with a
      median age of 16 years. Main diagnoses are persistent or extended oligoarticular
      JIA (33%), polyarticular JIA (30%), enthesitis-related JIA (21%) or systemic
      arthritis (15%). INTERVENTION: The transition programme comprises eight key
      components: (1) transition coordinator; (2) providing information and education;
      (3) availability by telephone; (4) information about and contact with an adult
      care programme; (5) guidance of parents; (6) meeting with peers; (7) transfer
      plan; and (8) actual transfer to adult care. PRIMARY AND SECONDARY OUTCOMES: The
      primary outcome is health status, as perceived by the adolescents. Secondary
      outcomes are health status, as perceived by the parents; medication adherence;
      illness-related knowledge; quality of life; fatigue; promotion of independence;
      support of autonomy; behavioural control and psychological control. RESULTS: At
      baseline, the median score was 69.2 (Q1=60.0;Q3=92.9) on psychosocial health and
      68.8 (Q1=56.3; Q3=89.1) on physical health. Rheumatic-specific health scores
      ranged from 62.5 to 100. CONCLUSIONS: We present the rationale and design of a
      study intended to evaluate a transition programme for adolescents with JIA as a
      brief intervention.

PMID- 24302503
TI  - Life expectancy estimation in small administrative areas with non-uniform
      population sizes: application to Australian New South Wales local government
      areas.
AB  - OBJECTIVE: To determine a practical approach for deriving life expectancy
      estimates in Australian New South Wales local government areas which display a
      large diversity in population sizes. DESIGN: Population-based study utilising
      mortality and estimated residential population data. SETTING: 153 local
      government areas in New South Wales, Australia. OUTCOME MEASURES: Key performance
      measures of Chiang II, Silcocks, adjusted Chiang II and Bayesian random effects
      model methodologies of life expectancy estimation including agreement analysis of
      life expectancy estimates and comparison of estimate SEs. RESULTS: Chiang II and
      Silcocks methods produced almost identical life expectancy estimates across a
      large range of population sizes but calculation failures and excessively large
      SEs limited their use in small populations. A population of 25 000 or greater was
      required to estimate life expectancy with SE of 1 year or less using adjusted
      Chiang II (a composite of Chiang II and Silcocks methods). Data aggregation
      offered some remedy for extending the use of adjusted Chiang II in small
      populations but reduced estimate currency. A recently developed Bayesian random
      effects model utilising the correlation in mortality rates between genders, age
      groups and geographical areas markedly improved the precision of life expectancy
      estimates in small populations. CONCLUSIONS: We propose a hybrid approach for the
      calculation of life expectancy using the Bayesian random effects model in
      populations of 25 000 or lower permitting the precise derivation of life
      expectancy in small populations. In populations above 25 000, we propose the use
      of adjusted Chiang II to guard against violations of spatial correlation, to
      benefit from a widely accepted method that is simpler to communicate to local
      health authorities and where its slight inferior performance compared with the
      Bayesian approach is of minor practical significance.

PMID- 24302504
TI  - Education level and survival after oesophageal cancer surgery: a prospective
      population-based cohort study.
AB  - OBJECTIVES: This study aimed to investigate whether a higher education level is
      associated with an improved long-term survival after oesophagectomy for cancer.
      DESIGN: A prospective, population-based cohort study. SETTING: Sweden-nationwide.
      PARTICIPANTS: 90% of all patients with oesophageal and cardia cancer who
      underwent a resection in Sweden in 2001-2005 were enrolled in this study (N=600;
      80.3% male) and followed up until death or the end of the study period (2012).
      The study exposure was level of education, defined as compulsory (<=9 years),
      moderate (10-12 years) or high (>=13 years). OUTCOME MEASURES: The main outcome
      measure was overall 5-year survival after oesophagectomy. Cox regression was used
      to estimate the associations between education level and mortality, expressed as
      HRs with 95% CIs, with adjustment for sex, age, tumour stage, histological type,
      complications, comorbidities and annual surgeon volume. The patient group with
      highest education was used as the reference category. RESULTS: Among the 600
      included patients, 281 (46.8%) had compulsory education, 238 (39.7%) had moderate
      education and 81 (13.5%) had high education. The overall 5-year survival rate was
      23.1%, 24.4% and 32.1% among patients with compulsory, moderate and high
      education, respectively. After adjustment for confounders, a slightly higher, yet
      not statistically significantly increased point HR was found among the compulsory
      educated patients (HR 1.08, 95% CI 0.80 to 1.47). In patients with tumour stage
      IV, increased adjusted HRs were found for compulsory (HR 2.88, 95% CI 1.07 to
      7.73) and moderately (HR 2.83, 95% CI 1.15 to 6.95) educated patients. No
      statistically significant associations were found for the other tumour stages.
      CONCLUSIONS: This study provides limited evidence of an association between lower
      education and worse long-term survival after oesophagectomy for cancer.

PMID- 24302505
TI  - Protocol for a prospective, controlled study of assertive and timely reperfusion
      for patients with ST-segment elevation myocardial infarction in Tamil Nadu: the
      TN-STEMI programme.
AB  - INTRODUCTION: Over the past two decades, India has witnessed a staggering
      increase in the incidence and mortality of ST-elevation myocardial infarction
      (STEMI). Indians have higher rates of STEMI and younger populations that suffer
      from it when compared with developed countries. Yet, the recommended reperfusion
      therapy with fibrinolysis and percutaneous coronary intervention is available
      only to a minority of patients. This gap in care is a result of financial
      barriers, limited healthcare infrastructure and poor knowledge and accessibility
      of acute medical services for a majority of its population. METHODS AND ANALYSIS:
      This is a prospective, multicentre, 'pretest/post-test' quasi-experimental,
      community-based study. This programme will use a 'hub-and-spoke' model of an
      integrated healthcare network based on clusters of primary-care health clinics,
      small hospitals and large tertiary-care facilities. It is an 'all-comers' study
      which will enrol consecutive patients presenting with STEMI to the participating
      hospitals. The primary objectives of the study is to improve the use of
      reperfusion therapy and reduce the time from first medical contact to device or
      drug in STEMI patients; and to increase the rates of early invasive risk
      stratification with coronary angiography within 3-24 h of fibrinolytic therapy in
      eligible patients through changes in process of care. Outcomes will be measured
      with statistical comparison made before and after implementing the TN-STEMI
      programme. The estimated sample size is based on the Kovai Erode Pilot study,
      which provided an initial work on establishing this type of programme in South
      India. It will be adequately powered at 80% with a superiority margin of 10% if
      36 patients are enrolled per cluster or 108 patients in three clusters. Thus, the
      enrolment period of 9 months will result in a sample size of 1500 patients.
      ETHICS: This study will be conducted in accordance with the ethical principles
      that have their origin in the current Declaration of Helsinki and 'ethical
      guidelines for biomedical research on human participants' as laid down by the
      Indian Council for Medical Research. All participating hospitals will still
      obtain local ethics committee approval of the study protocol and written informed
      consent will be obtained from all participants. DISSEMINATION AND RESULTS: Our
      findings will be reported through scientific publications, research conferences
      and public policy venues aimed at state and local governments in India. If
      successful, this model can be extended to other areas of India as well as serve
      as a model of STEMI systems of care for low-income and middle-income countries
      across the world. REGISTRATION: Trial is registered with Clinical trial registry
      of India, No: CTRI/2012/09/003002.

PMID- 24302506
TI  - Responses to concerns about child maltreatment: a qualitative study of GPs in
      England.
AB  - OBJECTIVES: To provide a rich description of current responses to concerns
      related to child maltreatment among a sample of English general practitioners
      (GPs). DESIGN: In-depth, face-to-face interviews (November 2010 to September
      2011). Participants selected and discussed families who had prompted
      'maltreatment-related concerns'. Thematic analysis of data. SETTING: 4 general
      practices in England. PARTICIPANTS: 14 GPs, 2 practice nurses and 2 health
      visitors from practices with at least 1 'expert' GP (expertise in child
      safeguarding/protection). RESULTS: The concerns about neglect and emotional abuse
      dominated the interviews. GPs described intense and long-term involvement with
      families with multiple social and medical problems. Narratives were distilled
      into seven possible actions that GPs took in response to maltreatment-related
      concerns. These were orientated towards whole families (monitoring and
      advocating), the parents (coaching) and children (opportune healthcare), and
      included referral to or working with other services and recording concerns.
      Facilitators of the seven actions were: trusting relationships between GPs and
      parents, good working relationships with health visitors and framing the
      problem/response as 'medical'. Narratives indicated significant time and energy
      spent building facilitating relationships with parents with the aim of improving
      the child's well-being. CONCLUSIONS: These GPs used core general practice skills
      for on-going management of families who prompted concerns about neglect and
      emotional abuse. Policy and research focus should be broadened to include
      strategies for direct intervention and on-going involvement by GPs, such as using
      their core skills during consultations and practice systems for monitoring
      families and encouraging presentation to general practice. Exemplars of current
      practice, such as those identified in our study, should be evaluated for
      feasibility and acceptability in representative general practice settings as well
      as tested for efficacy, safety and cost. The seven actions could form the basis
      for the 'lead professional' role in general practice as proposed in the 2013
      version of 'Working Together 'guidance.

PMID- 24302507
TI  - What do measures of agreement (kappa) tell us about quality of exposure
      assessment? Theoretical analysis and numerical simulation.
AB  - BACKGROUND: The reliability of binary exposure classification methods is
      routinely reported in occupational health literature because it is viewed as an
      important component of evaluating the trustworthiness of the exposure assessment
      by experts. The Kappa statistics (kappa) are typically employed to assess how
      well raters or classification systems agree in a variety of contexts, such as
      identifying exposed participants in a population-based epidemiological study of
      risks due to occupational exposures. However, the question we are really
      interested in is not so much the reliability of an exposure assessment method,
      although this holds value in itself, but the validity of the exposure estimates.
      The validity of binary classifiers can be expressed as a method's sensitivity
      (SN) and specificity (SP), estimated from its agreement with the error-free
      classifier. METHODS AND RESULTS: We describe a simulation-based method for
      deriving information on SN and SP that can be derived from kappa and the
      prevalence of exposure, since an analytic solution is not possible without
      restrictive assumptions. This work is illustrated in the context of comparison of
      job-exposure matrices assessing occupational exposures to polycyclic aromatic
      hydrocarbons. DISCUSSION: Our approach allows the investigators to evaluate how
      good their exposure-assessment methods truly are, not just how well they agree
      with each other, and should lead to incorporation of information of validity of
      expert assessment methods into formal uncertainty analyses in epidemiology.

PMID- 24302508
TI  - Primary prevention of diabetic retinopathy with fibrates: a retrospective,
      matched cohort study.
AB  - OBJECTIVES: To compare the progression of diabetic retinopathy (DR) in people
      with type 2 diabetes treated with fibrates with that of non-exposed controls.
      DESIGN: Retrospective, matched cohort study. SETTING: UK Clinical Practice
      Research Datalink (CPRD). PARTICIPANTS: 5038 people with type 2 diabetes with a
      history of fibrate exposure but without evidence of DR were identified. Three
      thousand one hundred and seventy-six (63%) people could be randomly matched to
      one non-exposed control; of these, 2599 (81.8%) were matched without any missing
      blood pressure or glycated haemoglobin (HbA1c) values. MAIN OUTCOME MEASURES: The
      primary endpoint was first recorded DR with a secondary endpoint of all-cause
      mortality or first DR. Time to clinical endpoints was compared using Cox
      proportional hazards models. RESULTS: Mean follow-up was 5.1 and 5.0 years for
      fibrate-exposed and non-exposed patients, respectively. For fibrate-exposed
      participants, there was a reduction in DR: 33.4 events/1000 person-years vs 40.4
      (p=0.002), and in death or DR: 50.6 vs 60.2 (p<0.001). For those matched with
      full systolic blood pressure and HbA1c data, crude event rates were 34.3 versus
      43.9 for DR (p<0.001) and 51.2 vs 63.4 (p<0.001) for death or DR. Following
      adjustment, DR was significantly delayed for those treated with fibrates, with an
      adjusted HR (aHR) of 0.785 (p<0.001) for participants with complete data and an
      aHR of 0.802 (p<0.001) for all participants. CONCLUSIONS: The treatment with
      fibrates in people with type 2 diabetes was independently associated with reduced
      progression to a first diagnosis of DR.

PMID- 24302510
TI  - 'Looking for the needle in the haystack': a qualitative study of the pathway to
      diagnosis of type 1 diabetes in children.
AB  - OBJECTIVE: To explore the pathway to diagnosis of type 1 diabetes (T1D) in
      children from the perspective of the child, family and general practitioner (GP).
      DESIGN: Qualitative interview study. PARTICIPANTS: Parents of children aged 1
      month to 16 years diagnosed with new onset T1D within the previous 3 months,
      children over 6 years diagnosed with new onset T1D within the previous 3 months
      and GPs who saw those children prior to diagnosis. SETTING: Children and parents
      were identified and recruited from two hospitals within the East of England.
      RESULTS: The parents of 16 children (2-16 years) were interviewed. The total
      interval from onset of symptoms to diagnosis ranged from 6 to 127 days. The
      appraisal interval was the longest for almost all children and the diagnostic
      interval the shortest. Even with some knowledge of T1D, it took many parents
      several weeks of a complex cyclical and iterative decision-making process and
      often a physical trigger, such as weight loss, to decide to consult a healthcare
      professional. By that stage, many had already made or suspected the diagnosis of
      T1D themselves. Five GPs were interviewed. They felt that the main challenges to
      diagnosing T1D in children were the rarity of the condition coupled with how well
      most of the children appeared, and the difficulty in obtaining urine or blood
      samples from children. CONCLUSIONS: This study highlights the difficulties for
      parents and GPs in recognising the early symptoms of T1D. It suggests that future
      interventions should be targeted at parents in the appraisal interval and include
      the importance of timely presentation to a healthcare professional and the
      differences between types 1 and 2 diabetes. Primary care physicians should also
      take parental concerns seriously and do urine dipstick tests during the
      consultation for children with symptoms of T1D.

PMID- 24302511
TI  - The role of private care in the interval between diagnosis and treatment of
      breast cancer in Northern Ireland: an analysis of Registry data.
AB  - OBJECTIVE: To examine the differences in the interval between diagnosis and
      initiation of treatment among women with breast cancer in Northern Ireland.
      DESIGN: A cross-sectional observational study. SETTING: All breast cancer care
      patients in the Northern Ireland Cancer Registry in 2006. PARTICIPANTS: All women
      diagnosed and treated for breast cancer in Northern Ireland in 2006. MAIN OUTCOME
      MEASURE: The number of days between diagnosis and initiation of treatment for
      breast cancer. RESULTS: The mean (median) interval between diagnosis and
      initiation of treatment among public patients was 19 (15) compared with 14 (12)
      among those whose care involved private providers. The differences between
      individual public providers were as marked as those between the public and
      private sector-the mean (median) ranging between 14 (12) and 25 (22) days.
      Multivariate models revealed that the differences were evident when a range of
      patient characteristics were controlled for including cancer stage. CONCLUSIONS:
      A relatively small number of women received care privately in Northern Ireland
      but experienced shorter intervals between diagnosis and initiation of treatment
      than those who received care wholly in the public system. The variation among
      public providers was as great as that between the public and private providers.
      The impact of such differences on survival and in light of waiting time targets
      introduced in Northern Ireland warrants investigation.

PMID- 24302509
TI  - Epidemiology and genetics of common mental disorders in the general population:
      the PEGASUS-Murcia project.
AB  - BACKGROUND: Multidisciplinary collaboration between clinicians, epidemiologists,
      neurogeneticists and statisticians on research projects has been encouraged to
      improve our knowledge of the complex mechanisms underlying the aetiology and
      burden of mental disorders. The PEGASUS-Murcia (Psychiatric Enquiry to General
      Population in Southeast Spain-Murcia) project was designed to assess the
      prevalence of common mental disorders and to identify the risk and protective
      factors, and it also included the collection of biological samples to study the
      gene-environmental interactions in the context of the World Mental Health Survey
      Initiative. METHODS AND ANALYSIS: The PEGASUS-Murcia project is a new cross
      sectional face-to-face interview survey based on a representative sample of non
      institutionalised adults in the Region of Murcia (Mediterranean Southeast,
      Spain). Trained lay interviewers used the latest version of the computer-assisted
      personal interview of the Composite International Diagnostic Interview (CIDI 3.0)
      for use in Spain, specifically adapted for the project. Two biological samples of
      buccal mucosal epithelium will be collected from each interviewed participant,
      one for DNA extraction for genomic and epigenomic analyses and the other to
      obtain mRNA for gene expression quantification. Several quality control
      procedures will be implemented to assure the highest reliability and validity of
      the data. This article describes the rationale, sampling methods and
      questionnaire content as well as the laboratory methodology. ETHICS AND
      DISSEMINATION: Informed consent will be obtained from all participants and a
      Regional Ethics Research Committee has approved the protocol. Results will be
      disseminated in peer-reviewed publications and presented at the national and the
      international conferences. DISCUSSION: Cross-sectional studies, which combine
      detailed personal information with biological data, offer new and exciting
      opportunities to study the gene-environmental interactions in the aetiology of
      common mental disorders in representative samples of the general population. A
      collaborative multidisciplinary research approach offers the potential to advance
      our knowledge of the underlying complex interactions and this opens the field for
      further innovative study designs in psychiatric epidemiology.

PMID- 24302512
TI  - Factors influencing trust in doctors: a community segmentation strategy for
      quality improvement in healthcare.
AB  - BACKGROUND: Trust is a forward-looking covenant between the patient and the
      doctor where the patient optimistically accepts his/her vulnerability. Trust is
      known to improve the clinical outcomes. OBJECTIVES: To explore the factors that
      determine patients' trust in doctors and to segment the community based on
      factors which drive their trust. SETTING: Resource-poor urban and rural settings
      in Tamil Nadu, a state in southern India. PARTICIPANTS: A questionnaire was
      administered to a sample of 625 adult community-dwelling respondents from four
      districts of Tamil Nadu, India, chosen by multistage sampling strategy. OUTCOME
      MEASURES: The outcomes were to understand the main domains of factors influencing
      trust in doctors and to segment the community based on which of these domains
      predominantly influenced their trust. RESULTS: Factor analysis revealed five main
      categories, namely, comfort with the doctor, doctor with personal involvement
      with the patient, behaviourally competent doctor, doctor with a simple appearance
      and culturally competent doctor, which explained 49.3% of the total variance.
      Using k-means cluster analysis the respondents were segmented into four groups,
      namely, those who have 'comfort-based trust', 'emotionally assessed trust', who
      were predominantly older and belonging to lower socioeconomic status, those who
      had 'personal trust', who were younger people from higher socioeconomic strata of
      the community and the group who had 'objectively assessed trust', who were
      younger women. CONCLUSIONS: Trust in doctors seems to be influenced by the
      doctor's behaviuor, perceived comfort levels, personal involvement with the
      patient, and to a lesser extent by cultural competence and doctor's physical
      appearance. On the basis of these dimensions, the community can be segmented into
      distinct groups, and trust building can happen in a strategic manner which may
      lead to improvement in perceived quality of care.

PMID- 24302513
TI  - The prevalence of Os acromiale: a systematic review and meta-analysis.
AB  - Os acromiale (OA) results from a failure of consolidation between the
      ossification centers of the acromial epiphysis. Its prevalence and its
      interactions with ancestry, gender, laterality, and side have been variously
      reported in the literature. The aims of this review are to provide an accurate
      estimate of OA prevalence and to investigate its association with other variables
      in an attempt to comprehend its etiology. Twenty-three studies met the inclusion
      criteria. The results of meta-analyses of large-sample studies revealed: (a) a
      crude overall prevalence of 7.0%, (b) a crude cadaveric prevalence of 7.6%, (c) a
      crude archeological (skeletal) prevalence of 5.6%, (d) a crude radiological
      prevalence of 4.2%, (e) a true anatomical prevalence of 9.6%, (f) a significantly
      higher frequency in persons of black ancestry than in persons of white, Native
      American and Middle Eastern ancestries (OR ~ 3), (g) significantly higher
      unilateral and bilateral frequencies in black ancestry (OR of 2 and 4,
      respectively), (h) nonsignificant interactions of OA frequency with gender and
      side. The commonest type of OA was the meso-acromion type (76.6%). Degenerative
      changes were present in 66.6% of OAs. The results of this evidence-based
      anatomical review support a genetic basis for OA rather than the mechanical
      trauma-induction hypothesis.

PMID- 24302514
TI  - Oxime ligation: a chemoselective click-type reaction for accessing
      multifunctional biomolecular constructs.
AB  - There is a growing need for biocompatible click reactions in order to prepare
      multifunctional conjugates, which are valuable molecules for innovative
      biomedical applications. In this context, we review the recent advances in the
      implementation of oxime ligation for the synthesis of multivalent or
      multicomponent systems. The value of these products is emphasized by their use in
      cell targeting, imaging, synthetic vaccines, and surface modifications. 

PMID- 24302515
TI  - Submillisecond mixing in a continuous-flow, microfluidic mixer utilizing mid
      infrared hyperspectral imaging detection.
AB  - We report a continuous-flow, microfluidic mixer utilizing mid-infrared
      hyperspectral imaging detection, with an experimentally determined,
      submillisecond mixing time. The simple and robust mixer design has the
      microfluidic channels cut through a polymer spacer that is sandwiched between two
      IR transparent windows. The mixer hydrodynamically focuses the sample stream with
      two side flow channels, squeezing it into a thin jet and initiating mixing
      through diffusion and advection. The detection system generates a mid-infrared
      hyperspectral absorbance image of the microfluidic sample stream. Calibration of
      the hyperspectral image yields the mid-IR absorbance spectrum of the sample
      versus time. A mixing time of 269 MUs was measured for a pD jump from 3.2 to
      above 4.5 in a D2O sample solution of adenosine monophosphate (AMP), which acts
      as an infrared pD indicator. The mixer was further characterized by comparing
      experimental results with a simulation of the mixing of an H2O sample stream with
      a D2O sheath flow, showing good agreement between the two. The IR microfluidic
      mixer eliminates the need for fluorescence labeling of proteins with bulky,
      interfering dyes, because it uses the intrinsic IR absorbance of the molecules of
      interest, and the structural specificity of IR spectroscopy to follow specific
      chemical changes such as the protonation state of AMP. 

PMID- 24302516
TI  - A growth-promoting signaling component cyclin D1 in neural stem cells has
      antiastrogliogenic function to execute self-renewal.
AB  - Self-renewing proliferation of neural stem cells (NSCs) is intimately linked to
      the inhibition of neuronal and glial differentiation, however, their molecular
      linkage has been poorly understood. We have proposed a model previously
      explaining partly this linkage, in which fibroblast growth factor 2 (FGF2) and
      Wnt signals cooperate to promote NSC self-renewal via beta-catenin accumulation,
      which leads to the promotion of proliferation by lymphoid enhancer factor (LEF)/T
      cell factor (TCF)-mediated cyclin D1 expression and at the same time to the
      inhibition of neuronal differentiation by beta-catenin-mediated potentiation of
      Notch signaling. To fully understand the mechanisms underlying NSC self-renewal,
      it needs to be clarified how these growth factor signals inhibit glial
      differentiation as well. Here, we demonstrate that cyclin D1, a NSC growth
      promoting signaling component and also a common component of FGF2 and Wnt
      signaling pathways, inhibits astroglial differentiation of NSCs. Interestingly,
      this effect of cyclin D1 is mediated even though its cell cycle progression
      activity is blocked. Forced downregulation of cyclin D1 enhances astrogliogenesis
      of NSCs in culture and in vivo. We further demonstrate that cyclin D1 binds to
      STAT3, a transcription factor downstream of astrogliogenic cytokines, and
      suppresses its transcriptional activity on the glial fibrillary acidic protein
      (Gfap) gene. Taken together with our previous finding, we provide a novel
      molecular mechanism for NSC self-renewal in which growth promoting signaling
      components activated by FGF2 and Wnts inhibit neuronal and glial differentiation.

PMID- 24302517
TI  - Well-being and perceived quality of life in elderly people displaced after the
      earthquake in L'Aquila, Italy.
AB  - On 6 April 2009, the city of L'Aquila was hit by a violent earthquake that
      destroyed almost all of its medieval centre, and the surviving inhabitants were
      evacuated and relocated in temporary quarters or undamaged homes. The aim of this
      study was to investigate the perceived quality of life of the elderly population
      3 years after the earthquake in relation to the social and logistic issues of new
      housing. The study was carried out between October 2011 and March 2012, and
      involved 571 subjects aged over 65 years living in the municipality of L'Aquila.
      The interviews took place in the surgeries of general practitioners and the
      city's Department of Prevention and Vaccination in the anti-influenza
      immunisation period. The instrument used was a 36-item questionnaire with closed,
      multiple choice answers divided into the following sections: demographics,
      everyday activities, health and perceived health, and the quality of life in the
      city. The results show that, 3 years after the earthquake, the elderly population
      living in the new towns and temporary housing of L'Aquila have a worse perception
      of their quality of life than the others. They feel a certain social isolation
      and wish to live elsewhere. Governments faced with the problems arising from a
      natural calamity should take into account all of the elements making up a good
      quality of life and, before making choices whose impact cannot be changed,
      consider both their immediate and long-term social consequences.

PMID- 24302518
TI  - Sonographic diagnosis of anatomical variations associated with carpal tunnel
      syndrome.
AB  - Bifid median nerve is an anatomic variation that occurs in about 18% of patients
      with symptoms suggestive of carpal tunnel syndrome and in about 15% of symptom
      free subjects. Reversed palmaris longus is a rare anatomic muscular variation.
      The simultaneous presence of a bifid median nerve and a reversed palmaris longus
      has been very rarely described, usually during surgical exploration or in
      cadavers. We present two cases where ultrasound showed the presence of both
      abnormalities, allowing a correct diagnosis and influencing the treatment plan.

PMID- 24302519
TI  - Structure and variation in ribosomal RNA genes of pea : Characterization of a
      cloned rDNA repeat and chromosomal rDNA variants.
AB  - A complete ribosomal DNA (rDNA) repeat unit has been cloned from the genome of
      Pisum sativum (garden pea) and used to construct a map containing a total of 58
      cleavage sites for 23 different restriction enzymes. Regions encoding 18s and 25s
      ribosomal RNA (rRNA) were identified by R-loop analysis. A 180 bp sequence
      element is repeated eight times in the intergenic 'nontranscribed spacer' (NTS)
      region, as defined by eight evenly spaced RsaI cleavage sites. Sequence
      heterogeneity among these elements (subrepeats) is indicated by the presence of
      an NcoI site within the five RsaI subrepeats distal to the 25s rRNA gene but not
      in the three subrepeats proximal to this gene, and also by the presence of an
      additional RsaI cleavage site in one subrepeat.The approximately 4000 copies of
      the rDNA repeat in the pea nuclear genome show considerable heterogeneity with
      respect to the length of the NTS region, and differences are also frequently
      observed between different genotypes. In both cases the length variation appears
      to be due primarily to differences in the number of subrepeat elements.Comparison
      of rDNA restriction maps for two pea genotypes separated for hundreds or perhaps
      thousands of generations reveals that they contain many rDNA identical repeat
      units. This data is consistent with the view that new rDNA variants are fixed
      only infrequently in the evolution of a species.Differences also exist between
      the rDNA repeats of a single genotype with respect to the degree of base
      modification at certain restriction sites. A large number of sites known to exist
      in the pea rDNA clone are not cleaved at all in genomic rDNA, or are cleaved in
      only some copies of the rDNA repeat. We believe these examples of incomplete
      cleavage results mostly from methylation, although it is difficult to rule out
      the possibility of sequence variation in all cases. Most putative modifications
      are best interpreted in terms of cytosine methylation in CG and CXG sequences,
      but at least one example is more consistent with adenine methylation.We also have
      constructed a more detailed restriction map of the wheat rDNA clone pTA71 and
      present a comparison of this map to our map of pea, pumpkin, and wheat in order
      to assess the amount of useful evolutionary information that can be obtained by
      comparison of such maps. 

PMID- 24302520
TI  - The effect of abscisic acid on the differential expression of alpha-amylase
      isozymes in barley aleurone layers.
AB  - The treatment of barley aleurone layers with gibberellic acid (GA3) results in
      the synthesis of two groups of alpha-amylase isozymes. Addition of abscisic acid
      (ABA) at the same time as GA3 inhibited the synthesis of both groups of isozymes.
      However, midcourse ABA addition (12 h or later after GA3) had a more inhibitory
      effect on the high pI alpha-amylase group than on the low pI alpha-amylase group.
      This midcourse inhibition was detectable within 2 h of ABA addition. Northern
      analysis results using cDNA probes for the high pI and low pI alpha-amylase
      groups paralleled the protein synthesis results for both isozyme groups. High pI
      alpha-amylase mRNA levels began to decrease within 2 h of midcourse ABA treatment
      and were less than 10% of the original level by 4 h. The levels of low pI alpha
      amylase mRNA were decreased less by midcourse ABA addition than were high pI mRNA
      levels. Cordycepin and cycloheximide blocked the effects of midcourse ABA
      addition on alpha-amylase mRNA. These observations indicate that ABA inhibits
      alpha-amylase expression at the pretranslational level and that protein and RNA
      synthesis are required for midcourse ABA action to occur. Our results also show
      that alpha-amylase mRNA, which has been thought to be very stable, is degraded
      after midcourse ABA treatment. 

PMID- 24302521
TI  - Plant cells do not properly recognize animal gene polyadenylation signals.
AB  - We have introduced chimeric genes containing polyadenylation signals from a human
      gene and two animal virus genes into tobacco cells. We see, in all three cases,
      inefficient and 'aberrant' utilization of the foreign polyadenylation signals. We
      find that a chimeric gene carrying the polyadenylation site of the human growth
      hormone gene is polyadenylated at three sites in the vicinity of the site that is
      polyadenylated in human cells. A chimeric gene containing the polyadenylation
      site from the adenovirus 5 E1A gene is polyadenylated at a site 11 bases
      downstream from that reported in animal cells. A gene carrying the
      polyadenylation site from the SV40 early region is polyadenylated some 80 bases
      upstream from the site that is polyadenylated in animal cells. In all three
      cases, related mRNAs ending at flanking 'authentic' plant polyadenylation sites
      can be detected, indicating that the foreign polyadenylation signals are
      inefficiently utilized in tobacco cells. 

PMID- 24302522
TI  - cDNA and protein sequence of a major pea seed albumin (PA 2 : Mr~26 000).
AB  - Pea albumin 2 (PA2:Mr~26000) is a major component of the albumin fraction derived
      from aqueous salt extracts of pea seed. Sodium dodecylsulfate-polyacrylamide gel
      electrophoresis and chromatography on DEAE-Sephacel resolve PA2 into two closely
      related components (PA2a and PA2b). A cDNA clone coding for one of these
      components has been sequenced and the deduced amino acid sequence compared with
      partial, chemically-determined sequences for cyanogen bromide peptides from both
      PA2 components. Complete amino acid sequences were obtained for the C-terminal
      peptides. The PA2 molecule of 230 amino acids contains four imperfect repeat
      sequences each of approximately 57 amino acids in length.The combined sequence
      data, together with a comparison of PA2-related polypeptides produced in vitro
      and in vivo, indicate that PA2 is synthesized without a signal sequence and does
      not undergo significant post-translational modification. Although both forms of
      PA2 contain Asn-X-Thr consensus sequences, neither form is glycosylated.
      Accumulation of PA2 contributes approximately 11% of the sulfur-amino acids in
      pea seeds (cysteine plus methionine equals 2.6 residues percent). Suppression of
      levels of PA2 polypeptides and their mRNAs in developing seeds of sulfur
      deficient plants is less marked than that for legumin, in spite of the lower
      content of sulfur-amino acids in legumin. 

PMID- 24302523
TI  - Isolation and sequence analysis of a nuclear tRNA(met-i) gene from soybean.
AB  - A gene encoding the initiator methionine transfer RNA (tRNA(met-i)) has been
      isolated from a soybean genomic library. The nucleotide sequence of the gene is
      colinear with the previously determined sequence of bean and wheat germ tRNA(met
      i) (3, 8) except for a transversion at site 51/63 in stem IV. Microinjection of
      the soybean gene into Xenopus oocytes caused the transcription of an RNA product
      equal in size to mature Xenopus tRNA(met-i). Hybridization of a restriction
      fragment containing the tRNA(met-i) gene to digests of soybean DNA reveals that
      the gene occurs in only one to a few copies per haploid genome. 

PMID- 24302524
TI  - A phytochrome regulated pea transcript encodes ferredoxin I.
AB  - We have sequenced the pea (cv. Alaska) cDNA clone pEA46 (16) and shown that it
      codes for ferredoxin I. This clone has previously been shown to correspond to a
      transcript whose levels are controlled by phytochrome (Kaufman et al. (1985)
      Plant Physiol. 78: 388-393; Thompson et al. (1983) Planta 158: 487-500).The
      deduced amino acid sequence includes part of an hydrophobic transit sequence that
      shows only very limited homology to that of Silene pratensis ferredoxin.Genomic
      blotting analysis indicates that ferredoxin I is encoded by one or two genes. A
      genomic clone (4601) has been isolated that contains the ferredoxin gene and at
      least 14 kb of flanking sequences. 

PMID- 24302525
TI  - Interspecies homology of nodulation genes in Rhizobium.
AB  - The internal structural portion of genes nodC and nodD (representatives of the
      two transcription units coding for common nodulation functions) and of hsnB and
      hsnD (genes from the two transcription units determining host-specificity of
      nodulation) have been cloned from Rhizobium meliloti into M13 vectors and used as
      probes against genomic DNAs from different Rhizobium strains and species. nodC
      and nodD were found in all species with one exception, indicating that they are
      common and widely spread genes, though the nodD gene hybridized only very weakly
      with slow-growing rhizobia. Interestingly, reiteration of nodD sequences was
      observed in almost all fast-growing strains (with the exception of R.
      leguminosarum). hsnB and, more so, hsnD are present only in a few species tested,
      supporting their specific involvement in R. meliloti-Medicago sativa symbiosis.
      In several cases the hybridizing bands from total Rhizobium DNA were compared to
      those found in recombinant plasmids carrying functional nodulation regions, and
      these analyses supported the notion that the bands indicate the presence of
      functional genes. 

PMID- 24302526
TI  - cDNA cloning of mRNAs induced in resistant barley during infection by Erysiphe
      graminis f.sp. Hordei.
AB  - Near-isogenic cultivars of Hordeum vulgare which differ for the Mlp gene for
      resistance to Erysiphe graminis f.sp. hordei were inoculated with race 3 of this
      pathogen and in vitro translation products of mRNA populations compared by 2
      dimensional gel electrophoresis and fluorography. This revealed the presence of
      new mRNA species in infected leaves compared to non-inoculated controls. These
      new mRNA species were more abundant in resistant leaves than susceptible leaves.
      A cDNA library was prepared from poly(A)(+)RNA isolated from infected leaves
      carrying the Mlp gene for resistance (cvMlp). The library was screened by
      differential hybridization using [(32)P]-labelled cDNA prepared from
      poly(A)(+)RNA of both control and infected leaves. Six cDNA clones showing
      greater hybridization to cDNA prepared from infected leaves were selected. These
      six cDNA clones hybridized to DNA isolated from barley leaves but not to DNA from
      conidia of the fungus. In Northern blot analysis of RNA from infected leaves the
      six cDNA clones each hybridized to mRNA species of different size. Translation
      products for three of the cDNA clones corresponded to infection-related
      translation products identified on 2-dimensional fluorograms. The cDNA clones
      were used to study the kinetics of host mRNA induction during infection of the
      near-isogenic cultivars of barley. The host mRNA species corresponding to the
      cDNA clones were induced prior to 24 h after inoculation during the primary
      penetration processes. In addition the mRNAs corresponding to four of the cDNA
      clones increased to greater amounts in cvMlp than in the near-isogenic
      susceptible cultivar (cvmlp) over a 2-d period following inoculation. These
      results suggest that the Mlp gene has a regulatory role in host gene expression
      resulting in enhanced expression of several host mRNA species following infection
      by the powdery mildew fungus. 

PMID- 24302527
TI  - Elevated amounts of methotrexate-binding protein, different from normal
      dihydrofolate reductase, in a petunia MTX(R)-cell line.
AB  - A petunia cell line, 1ECB, was previously isolated by the stepwise selection
      procedure, for resistance to methotrexate (MTX), an antimetabolite for the enzyme
      dihydrofolate reductase (DHFR). Using ammonium sulfate precipitates of cell
      lysates of cell line 1ECB and its parental cell line (WT), it was found that the
      mutant has an increase of 400 fold in (3)H-MTX binding capacity and a decrease in
      the affinity for MTX binding, at two orders of magnitude, in comparison with the
      WT. In addition, the DHFR specific activity in the mutant increased only
      moderately (5- to 10-fold), this activity is extremely sensitive to MTX
      inhibition as compared to the WT. It is evident that the MTX resistance of line
      1ECB results mainly from overproduction of an MTX-binding protein which differs
      from the WT DHFR by four biochemical criteria. This protein may serve as a trap
      for the excess amounts of MTX to which the cells are exposed. 

PMID- 24302528
TI  - Functional analysis of the Agrobacterium tumefaciens octopine Ti-plasmid left and
      right T-region border fragments.
AB  - Border fragments of the octopine Ti-plasmid were tested for their ability to
      restore tumorigenicity of an avirulent mutant carrying a deleted right border. It
      was found that neither introduction of left border fragments nor that of small
      right border fragments at the position of the deletion resulted in a complete
      restoration of oncogenicity. However, insertion of a larger right border fragment
      in the deletion mutant gave fully oncogenic strains. In the latter case sequences
      to the right side of the right border repeat were found to be responsible for a
      complete restoration of oncogenicity. Also a left border repeat inserted together
      with this enhancer sequence fully restored the oncogenicity of the deletion
      mutant. The enhancer-sequence on itself was not able to mediate the transfer of
      the T-region to the plant cell. Border fragments inserted in inverted orientation
      in the deletion mutant were able to mediate the transfer of the T-region to the
      plant cell, but at a reduced frequency. 

PMID- 24302529
TI  - Chromosomal nodulation genes: Sym-plasmid containing Agrobacterium strains need
      chromosomal virulence genes (chvA and chvB) for nodulation.
AB  - The chromosomal genes chvA and chvB of Agrobacterium tumefaciens, which mediate
      attachment to plant cells, were found to be essential not only for tumour
      induction but also for the formation of root nodules on plants. 

PMID- 24302530
TI  - Is the demographic dividend an education dividend?
AB  - The effect of changes in age structure on economic growth has been widely studied
      in the demography and population economics literature. The beneficial effect of
      changes in age structure after a decrease in fertility has become known as the
      "demographic dividend." In this article, we reassess the empirical evidence on
      the associations among economic growth, changes in age structure, labor force
      participation, and educational attainment. Using a global panel of countries, we
      find that after the effect of human capital dynamics is controlled for, no
      evidence exists that changes in age structure affect labor productivity. Our
      results imply that improvements in educational attainment are the key to
      explaining productivity and income growth and that a substantial portion of the
      demographic dividend is an education dividend. 

PMID- 24302531
TI  - Reduced intensity conditioning in allogeneic stem cell transplantation for AML
      with Down syndrome.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) has not been widely
      used in patients with acute myeloid leukemia (AML) and Down syndrome (DS) due to
      fear of transplantation-related toxicity. A retrospective analysis of the outcome
      of allogeneic HSCT was conducted in 15 patients with AML and DS. The five
      patients transplanted with the reduced intensity conditioning (4 in complete
      remission (CR) and 1 in non-CR) had a significantly better survival rate than 10
      patients transplanted with a conventional conditioning (4 in CR and 6 in non-CR)
      (3-year EFS (95% confidence interval): 80.0% (20.4-96.9%) vs. 10.0% (0.6%-35.8%),
      P = 0.039).

PMID- 24302532
TI  - Mechanism of intramolecular photostabilization in self-healing cyanine
      fluorophores.
AB  - Organic fluorophores, which are popular labels for microscopy applications,
      intrinsically suffer from transient and irreversible excursions to dark-states.
      An alternative to adding photostabilizers at high concentrations to the imaging
      buffer relies on the direct linkage to the fluorophore. However, the working
      principles of this approach are not yet fully understood. In this contribution,
      we investigate the mechanism of intramolecular photostabilization in self-healing
      cyanines, in which photodamage is automatically repaired. Experimental evidence
      is provided to demonstrate that a single photostabilizer, that is, the vitamin E
      derivative Trolox, efficiently heals the cyanine fluorophore Cy5 in the absence
      of any photostabilizers in solution. A plausible mechanism is that Trolox
      interacts with the fluorophore through intramolecular quenching of triplet
      related dark-states, which is a mechanism that appears to be common for both
      triplet-state quenchers (cyclooctatetraene) and redox-active compounds (Trolox,
      ascorbic acid, methylviologen). Additionally, the influence of solution
      additives, such as cysteamine and procatechuic acid, on the self-healing process
      are studied. The results suggest the potential applicability of self-healing
      fluorophores in stochastic optical reconstruction microscopy (STORM) with optical
      super-resolution. The presented data contributes to an improved understanding of
      the mechanism involved in intramolecular photostabilization and has high
      relevance for the future development of self-healing fluorophores, including
      their applications in various research fields. 

PMID- 24302533
TI  - Interventions for preventing blood loss during the treatment of cervical
      intraepithelial neoplasia.
AB  - BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre
      malignant lesion. Surgical treatments for CIN are commonly associated with blood
      loss. OBJECTIVES: To assess the effectiveness and safety of interventions for
      preventing blood loss during the treatment of CIN. SEARCH METHODS: We searched
      the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and
      CENTRAL up to November 2012. We also searched registers of clinical trials,
      abstracts of scientific meetings and reference lists of included studies.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of vasopressin,
      tranexamic acid, haemostatic sutures, Amino-Cerv or Monsel's solution in women
      undergoing surgery for CIN. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently abstracted data and assessed risk of bias. Risk ratios comparing
      adverse events in women who received one of the interventions were pooled in a
      random-effects meta-analyses or included in single trial analyses. MAIN RESULTS:
      Twelve RCTs (N = 1602, of whom 1512 were assessed) were included.Vasopressin
      significantly reduced perioperative bleeding (mean difference (MD) = -100.80, 95%
      confidence interval (CI) -129.48 to -72.12) and was associated with a decreased
      risk of bleeding that required haemostatic sutures or further vasopressin,
      compared to placebo (risk ratio (RR) = 0.39, 95% CI 0.27 to 0.56).Tranexamic acid
      significantly reduced risk of secondary haemorrhage (RR = 0.23, 95% CI 0.11 to
      0.50), but not primary haemorrhage (RR = 1.24, 95% CI 0.04 to 38.23) after knife
      and laser cone biopsy, compared with placebo. There was also a statistically
      significant reduction in postoperative blood loss compared with placebo (MD = 
      55.60, 95% CI -94.91 to -16.29).Packing with Monsel's solution resulted in less
      perioperative blood loss (MD = -22.00, 95% CI -23.09 to -20.91) and decreased the
      risk of dysmenorrhoea (RR = 0.37, 95% CI 0.16 to 0.84), unsatisfactory colposcopy
      (RR = 0.43, 95% CI 0.30 to 0.63) and cervical stenosis (RR = 0.35, 95% CI 0.25 to
      0.49) compared to routine suturing, but was not statistically different to
      sutures for risk of primary and secondary haemorrhages.Amino-Cerv antibiotic gel
      failed to make a difference on secondary haemorrhage but was associated with
      significantly less vaginal discharge at 2 weeks compared with routine care (RR =
      0.27, 95% CI 0.09 to 0.86).There was no significant difference in blood loss
      between women who received ball electrode diathermy and those who received
      Monsel's paste (MD = 4.82, 95% CI -3.45 to 13.09). AUTHORS' CONCLUSIONS: Bleeding
      associated with surgery of the cervix appears to be reduced by vasopressin, used
      in combination with local anaesthetic. Tranexamic acid appears to be beneficial
      after knife and laser cone biopsy. There are insufficient data to assess the
      effects on primary haemorrhage. There is some evidence that haemostatic suturing
      has an adverse effect on blood loss, cervical stenosis and satisfactory
      colposcopy.

PMID- 24302534
TI  - Ontogeny of sexual size dimorphism and environmental quality in Guatemalan
      children.
AB  - OBJECTIVES: Human growth data from Guatemalan school children were analyzed to
      test the hypothesis that the degree of sexual size dimorphism (SSD) in height is
      reduced for people living under more adverse environmental quality. METHODS: The
      sample consists of 2,560 girls and 3,262 boys, 6-16.99 years of age, from the two
      major Guatemalan ethnic groups, Maya of very low socioeconomic status (SES) and
      Ladino of high, middle, and low SES. SES was estimated by questionnaire and
      ethnographic observation. All data are from the Longitudinal Study of Child
      Development of the Universidad del Valle de Guatemala. Significance of SSD was
      tested within each whole year age category (e.g., 6.0-6.9 years) by SES for
      Ladinos and Maya. Ethnic groups were then compared for each age category to
      determine whether the SSD values were significantly different between groups.
      RESULTS: Statistically significant height SSD was found for 10 of the 11 age
      categories for the high SES Ladinos, 8 of the 11 age categories for middle SES
      Ladinos, 3 of the 11 low SES Ladino age categories, and 0 of the 11 very low SES
      Maya age categories. For all SES and ethnic groups SSD tended to decrease between
      6 and 11 years of age and then increase after age 12 years. CONCLUSIONS: A poor
      quality environment for growth and development, as estimated by SES, was found to
      reduce or eliminate statistically significant SSD. Patterns of biological
      maturation before and after puberty also seem to contribute to age changes in
      SSD.

PMID- 24302535
TI  - Semiparametric varying-coefficient model for interval censored data with a cured
      proportion.
AB  - Varying-coefficient models have claimed an increasing portion of statistical
      research and are now applied to censored data analysis in medical studies. We
      incorporate such flexible semiparametric regression tools for interval censored
      data with a cured proportion. We adopted a two-part model to describe the overall
      survival experience for such complicated data. To fit the unknown functional
      components in the model, we take the local polynomial approach with bandwidth
      chosen by cross-validation. We establish consistency and asymptotic distribution
      of the estimation and propose to use bootstrap for inference. We constructed a
      BIC-type model selection method to recommend an appropriate specification of
      parametric and nonparametric components in the model. We conducted extensive
      simulations to assess the performance of our methods. An application on a
      decompression sickness data illustrates our methods.

PMID- 24302536
TI  - Impact of pediatric mental health screening on clinical discussion and referral
      for services.
AB  - OBJECTIVE: This study discusses the impact of mental health screening in
      pediatric primary care on the management of mental health concerns. METHODS:
      Youth aged 11 years and their parents completed the Pediatric Symptom Checklist
      and chart reviews were used to gather information about discussion of mental
      health concerns and connection with mental health services. The study design was
      a post-intervention study with a concurrent comparison group of youth aged 12
      years who were not offered a screening. The chi(2) or Fisher's exact tests and
      logistic regression were used to compare groups on outcome variables. RESULTS:
      Parents who completed a mental health screening for their child were more likely
      to be referred and attend mental health services, attend a psychiatrist
      appointment, and discuss their concerns with the primary care provider compared
      with the comparison group. CONCLUSIONS: Screening by parents improves detection
      of problems and fosters conversations with providers and subsequent connection
      with services.

PMID- 24302537
TI  - Information theoretic ranking of four models of diffusion attenuation in fresh
      and fixed prostate tissue ex vivo.
AB  - PURPOSE: To compare the theoretical information content of four popular models of
      diffusion-weighted signal attenuation. METHOD: Four whole prostates were imaged
      fresh unfixed and fixed at 9.4T. Biexponential, kurtosis, stretched exponential,
      and monoexponential models were ranked using Akaike's Information Criterion (AIC)
      with validation by a leave-one-out test of model prediction error. RESULTS: For
      unfixed tissue measurements (b-value range: 17-2104 s/mm(2)) the biexponential
      and kurtosis models had similar information content to each other and this was
      distinctly higher than for the stretched and monoexponential models. In fixed
      tissue measurements (b-value range: 17-8252 s/mm(2)), the biexponential model had
      much higher information content than the three other models. CONCLUSION: AIC
      based model ranking is consistent with an independent prediction accuracy test.
      Biexponential and kurtosis models consistently perform better than stretched and
      monoexponential models. The biexponential model has increasing superiority over
      all three other models as maximum b-value increases above ~2000 s/mm(2).

PMID- 24302538
TI  - A comparison of relative and cause-specific survival by cancer site, age and time
      since diagnosis.
AB  - Relative survival (RS) estimates are widely used by cancer registries, mainly
      because they do not rely on the well-documented deficiencies of cause of death
      information. The aim of our study was to compare 5-year cause-specific survival
      (CSS) estimates and 5-year RS estimates for different cancer sites by age and
      time since diagnosis, and discuss possible reasons for observed differences.
      Using data from the Cancer Registry of Norway, we identified 200,008 patients
      diagnosed with cancer at one of the 48 sites included in this analysis during the
      period 1996-2005, and followed them up until the end of 2010. CSS estimates were
      calculated (i) considering cause of death to be the cancer that was originally
      diagnosed and (ii) considering the cause of death to be a cancer within the same
      organ system. For most cancer sites the difference between CSS and RS estimates
      was small (<5%). The greatest differences were seen for rarer cancers such as
      mediastinum and Kaposi sarcoma. Including deaths from the same organ system in
      the calculation of CSS further reduced the differences for many sites. For
      younger age groups and shorter time since diagnosis, RS and CSS estimates tended
      to be similar, whereas CSS estimates tended to be lower than RS estimates with
      longer time since diagnosis in the oldest age groups. When compared to RS
      estimates CSS estimates were reliable for most of the cancer sites included in
      our analysis. There are, however, some exceptions where CSS estimates may not be
      recommended, including for rarer cancers and for patients aged 85 and above. 

PMID- 24302539
TI  - Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor
      progression.
AB  - The identity of the cells that contribute to brain tumor structure and
      progression remains unclear. Mesenchymal stem cells (MSCs) have recently been
      isolated from normal mouse brain. Here, we report the infiltration of MSC-like
      cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal
      stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-)
      and have multipotent differentiation capacity. We show that the infiltration of
      BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the
      proliferation rate of GL261 cells in vitro. For the first time, we report that
      the majority of GL261 cells expressed mesenchymal phenotype under both adherent
      and sphere culture conditions in vitro and that the non-MSC population is
      nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal
      phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in
      both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic
      mice and GL261-GFP cells inoculated into wild-type mice. We show the expression
      of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations.
      In vivo, the GL261 cells change marker profile and acquire a phenotype that is
      more similar to cells growing in sphere culture conditions. Finally, we identify
      a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly
      isolated and culture-expanded cells. Our data indicate that cells with MSC-like
      phenotype infiltrate into the tumor stroma and play an important role in tumor
      cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could
      be a possible strategy for treating glioblastoma patients.

PMID- 24302540
TI  - Enantiomerization and enantioselective bioaccumulation of metalaxyl in Tenebrio
      molitor larvae.
AB  - The enantiomerization and enantioselective bioaccumulation of metalaxyl by a
      single dose of exposure to Tenebrio molitor larvae under laboratory condition
      were studied by high-performance liquid chromatography tandem mass spectroscopy
      (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5-dichlorophenyl
      carbamate)] column. Exposure of enantiopure R-metalaxyl and S-metalaxyl in
      Tenebrio molitor larvae exhibited significant enantiomerization, with formation
      of the R enantiomers from the S enantiomers, and vice versa, which might be
      attributed to the chiral pesticide catalyzed by a certain enzyme in Tenebrio
      molitor larvae. Enantiomerization was not observed in wheat bran during the
      period of 21 d. In addition, bioaccumulation of rac-metalaxyl in Tenebrio molitor
      larvae was enantioselective with a preferential accumulation of S-metalaxyl.
      These results showed that enantioselectivity was caused not only by actual
      degradation and metabolism but also by enantiomerization, which was an important
      process in the environmental fate and behavior of metalaxyl enantiomers.

PMID- 24302541
TI  - Synthesis of triple-layered Ag@Co@Ni core-shell nanoparticles for the catalytic
      dehydrogenation of ammonia borane.
AB  - Triple-layered Ag@Co@Ni core-shell nanoparticles (NPs) containing a silver core,
      a cobalt inner shell, and a nickel outer shell were formed by an in situ chemical
      reduction method. The thickness of the double shells varied with different cobalt
      and nickel contents. Ag0.04 @Co0.48 @Ni0.48 showed the most distinct core-shell
      structure. Compared with its bimetallic core-shell counterparts, this catalyst
      showed higher catalytic activity for the hydrolysis of NH3 BH3 (AB). The
      synergetic interaction between Co and Ni in Ag0.04 @Co0.48 @Ni0.48 NPs may play a
      critical role in the enhanced catalytic activity. Furthermore, cobalt-nickel
      double shells surrounding the silver core in the special triple-layered core
      shell structure provided increasing amounts of active sites on the surface to
      facilitate the catalytic reaction. These promising catalysts may lead to
      applications for AB in the field of fuel cells. 

PMID- 24302543
TI  - Use of traditional and complementary/alternative medicine (TCAM) in children with
      cancer in Guatemala.

PMID- 24302542
TI  - Genetically predicted testosterone and cardiovascular risk factors in men: a
      Mendelian randomization analysis in the Guangzhou Biobank Cohort Study.
AB  - BACKGROUND: Observationally lower testosterone is associated with an unhealthier
      cardiovascular (CVD) risk profile, but this association is open to confounding
      and reverse causality. The authors examined the association of testosterone with
      well-established cardiovascular disease (CVD) risk factors (blood pressure, low
      density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol
      and fasting glucose) and the Framingham score using a Mendelian randomization
      analysis with a separate-sample instrumental variable estimator. METHODS: To
      minimize reverse causality, a genetic score predicting testosterone was developed
      in 289 young Chinese men from Hong Kong, based on three selected testosterone
      related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031).
      Multivariable censored and linear regressions were used to examine the
      association of genetically predicted testosterone levels with CVD risk factors
      and Framingham score among 4212 older Chinese men from the Guangzhou Biobank
      Cohort Study. RESULTS: Predicted testosterone was unrelated to systolic blood
      pressure [-0.11 mmHg, 95% confidence interval (CI) -0.70 to 0.48], diastolic
      blood pressure (0.04 mmHg, 95% CI -0.27 to 0.36), fasting glucose (0.02 mmol/l,
      95% CI -0.02 to 0.06) or Framingham score (0.02, 95% CI -0.0001 to 0.03) but
      associated with higher LDL-cholesterol (0.02 mmol/l, 95% CI 0.01 to 0.04) and
      lower HDL-cholesterol (-0.01 mmol/l, 95% CI -0.02 to -0.001), after adjustment
      for potential confounders (age, education, smoking status, use of alcohol and
      body mass index). CONCLUSIONS: Our findings did not corroborate observed
      protective effects of testosterone on cardiovascular risk factors or risk of
      ischaemic heart disease among men, but raises the possibility that higher
      testosterone may be associated with an unhealthier lipid profile.

PMID- 24302544
TI  - The role of cortisol and psychopathic traits in aggression among at-risk girls:
      tests of mediating hypotheses.
AB  - Multiple etiological factors (e.g., biological and personality predispositions)
      have been linked to the development of aggression. The purpose of the present
      study was to examine the relation between proactive/reactive aggression and
      biological (HPA-axis functioning) and personality characteristics (subdimensions
      of psychopathy) among girls at risk for aggressive behavior. Participants
      included girls (N = 158) admitted for acute psychiatric inpatient treatment (M
      age = 9.72; SD = 1.99). Parents completed a measure of proactive/reactive
      aggression and psychopathy upon admission. Fasting plasma cortisol levels were
      obtained the morning following the child's admission. Correlational analyses
      revealed a significant negative correlation between cortisol and the narcissism
      and impulsivity subdimensions of psychopathy as well as proactive/reactive
      aggression. A significant positive relation between proactive and reactive
      aggression and the three subdimensions of psychopathy was also observed. Path
      analyses revealed that only narcissism was uniquely and positively related to
      proactive and reactive aggression. Tests of indirect effects from cortisol to
      aggression through subdimensions of psychopathy indicated significant pathways
      via narcissism to proactive and reactive aggression. The findings support
      previous research linking narcissism uniquely to aggression for girls and suggest
      that the relation between cortisol and proactive/reactive aggression is mediated
      by narcissism.

PMID- 24302545
TI  - Diffusion and perfusion MRI prediction of progression-free survival in patients
      with hepatocellular carcinoma treated with concurrent chemoradiotherapy.
AB  - PURPOSE: To assess whether MR perfusion and diffusion parameters taken before
      concurrent chemoradiotherapy (CCRT) are useful imaging biomarkers for predicting
      progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Twenty patients with locally advanced HCC who had no
      treatment before CCRT underwent dynamic contrast-enhanced (DCE) and diffusion
      weighted MRI. Mean values of the volume transfer constant (K(trans) ), reflex
      constant (Kep ), extravascular extracellular volume fraction (Ve ) and the
      apparent diffusion coefficient (ADC) were estimated on a region of interest. The
      best cutoff value for each factor was assessed to differentiate between patients
      who had PFS shorter or longer than the median PFS. Patients were dichotomized in
      terms of the cutoff value. The survival outcome of the two groups and the
      predictive ability of each factor on PFS were evaluated. RESULTS: Median time to
      PFS was 179 days. The best cutoff values for ADC, K(trans) , Kep , and Ve was
      1.008 * 10(-3) mm(2) s(-1) , 0.108 min(-1) , 0.570 min(-1) , and 0.298%. Patients
      with higher ADC had significantly longer PFS than those with lower ADC(P <
      0.0001). CONCLUSION: The ADC of HCC acquired before CCRT correlated with PFS and
      was valuable in the prediction of the clinical outcome of HCC treated with CCRT.

PMID- 24302546
TI  - Surgery for cervical intraepithelial neoplasia.
AB  - BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre
      malignant lesion. Atypical squamous changes occur in the transformation zone of
      the cervix with mild, moderate or severe changes described by their depth (CIN 1,
      2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower
      morbidity excision techniques. Choice of treatment depends on the grade and
      extent of the disease. OBJECTIVES: To assess the effectiveness and safety of
      alternative surgical treatments for CIN. SEARCH METHODS: We searched the Cochrane
      Gynaecological Cancer Group Trials Register, Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to
      November 2012). We also searched registers of clinical trials, abstracts of
      scientific meetings and reference lists of included studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) of alternative surgical treatments in women
      with cervical intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review
      authors independently abstracted data and assessed risks of bias. Risk ratios
      that compared residual disease after the follow-up examination and adverse events
      in women who received one of either laser ablation, laser conisation, large loop
      excision of the transformation zone (LLETZ), knife conisation or cryotherapy were
      pooled in random-effects model meta-analyses. MAIN RESULTS: Twenty-nine trials
      were included. Seven surgical techniques were tested in various comparisons. No
      significant differences in treatment failures were demonstrated in terms of
      persistent disease after treatment. Large loop excision of the transformation
      zone appeared to provide the most reliable specimens for histology with the least
      morbidity. Morbidity was lower than with laser conisation, although the trials
      did not provide data for every outcome measure. There were not enough data to
      assess the effect on morbidity when compared with laser ablation. AUTHORS'
      CONCLUSIONS: The evidence suggests that there is no obvious superior surgical
      technique for treating cervical intraepithelial neoplasia in terms of treatment
      failures or operative morbidity.

PMID- 24302547
TI  - High-temperature elastic moduli of flux-grown alpha-GeO2 single crystal.
AB  - From high-precision Brillouin spectroscopy measurements, six elastic constants
      (C11, C33, C44, C66, C12, and C14) of a flux-grown GeO2 single crystal with the
      alpha-quartz-like structure are obtained in the 298-1273 K temperature range.
      High-temperature powder X-ray diffraction data is collected to determine the
      temperature dependence of the lattice parameters and the volume thermal expansion
      coefficients. The temperature dependence of the mass density, rho, is evaluated
      and used to estimate the thermal dependence of its refractive indices (ordinary
      and extraordinary), according to the Lorentz-Lorenz equation. The extraction of
      the ambient piezoelectric stress contribution, e11, from the C'11-C11 difference
      gives, for the piezoelectric strain coefficient d11 , a value of 5.7(2) pC N(-1),
      which is more than twice that of alpha-quartz. As the quartz structure of alpha
      GeO2 remains stable until melting, piezoelectric activity is observed until 1273
      K.

PMID- 24302549
TI  - A missense polymorphism in ATF6 gene is associated with susceptibility to
      hepatocellular carcinoma probably by altering ATF6 level.
AB  - Accumulated evidences indicate that single nucleotide polymorphisms (SNP) are
      associated with risk of hepatocellular carcinoma (HCC). Activating transcription
      factor 6 (ATF6) is an important modulator of the unfolded protein response (UPR),
      which is regarded to be involved in carcinogenesis. So we speculate that SNPs in
      ATF6 may be associated with susceptibility to HCC. We carried out a two-stage
      association study in three independent case-control groups in a total of 1,082
      chronic hepatitis B (CHB) patients and 816 hepatitis B virus (HBV) related HCC
      patients in Han Chinese. Four SNPs which can represent all potential functional
      SNPs with MAF > 0.1 recorded in HapMap database in ATF6 gene were genotyped using
      TaqMan methods. Functional analyses were conducted to verify the biological
      significances of the associated SNP. We identified a missense SNP (rs2070150) was
      significantly associated with susceptibility to HCC (p = 0.008, 0.001 and 0.007
      in Beijing_302, Beijing_You'an and Guangxi samples, respectively). This SNP was
      further validated in four independent groups of major HBV outcomes, indicating it
      may associate exclusively to HCC. ATF6 mRNA expression was significantly
      decreased as the disease progressed (p <0.001). Functional analyses show that the
      protective allele of rs2070150 could significantly increase the expression levels
      of ATF6 mRNA, as well as ATF6 regulated genes such as GRP78, XBP1 and CHOP. These
      findings indicate that a common missense SNP in ATF6 may contribute to
      susceptibility of HCC functionally. 

PMID- 24302550
TI  - Evaluation of the toxicity of food additive silica nanoparticles on
      gastrointestinal cells.
AB  - Silica nanoparticles (NPs) have been widely used in food products as an additive;
      however, their toxicity and safety to the human body and the environment still
      remain unclear. As a food additive, silica NPs firstly enter the human
      gastrointestinal tract along with food, thus their gastrointestinal toxicity
      deserves thorough study. Herein, we evaluated the toxicity of food additive
      silica NPs to cells originating from the gastrointestinal tract. Four silica NP
      samples were introduced to human gastric epithelial cell GES-1 and colorectal
      adenocarcinoma cell Caco-2 to investigate the effect of silica sample, exposure
      dose and exposure period on the morphology, viability and membrane integrity of
      cells. The cell uptake, cellular reactive oxygen species (ROS) level, cell cycle
      and apoptosis were determined to reveal the toxicity mechanism. The results
      indicate that all four silica NPs are safe for both GES-1 and Caco-2 cells after
      24-h exposure at a concentration lower than 100 ug ml(-1) . At a higher
      concentration and longer exposure period, silica NPs do not induce the
      apoptosis/necrosis of cells, but arrest cell cycle and inhibit the cell growth.
      Notably, silica NPs do not pass through the Caco-2 cell monolayer after 4-h
      contact, indicating the low potential of silica NPs to cross the gastrointestinal
      tract in vivo. Our findings indicate that silica NPs could be used as a safe food
      additive, but more investigations, such as long-term in vivo exposure, are
      necessary in future studies.

PMID- 24302551
TI  - Self-assembly of three-dimensional supramolecular polymers through cooperative
      tetrathiafulvalene radical cation dimerization.
AB  - The self-assembly of a new type of three-dimensional (3D) supramolecular polymers
      from tetrahedral monomers in both organic and aqueous media is described. We have
      designed and synthesized two tetraphenylmethane derivatives T1 and T2, both of
      which bear four tetrathiafulvalene (TTF) units. When the TTF units were oxidized
      to the radical cation TTF(.+) , their pre-organized tetrahedral arrangement
      remarkably enhanced their intermolecular dimerization, leading to the formation
      of new 3D spherical supramolecular polymers. The structure of the supramolecular
      polymers has been inferred on the basis of UV/Vis absorption, electron
      paramagnetic resonance, cyclic voltammetry, and dynamic light scattering (DLS)
      analysis, as well as by comparing these properties with those of the self
      assembled structures of mono-, di-, and tritopic control compounds. DLS
      experiments revealed that the spherical supramolecular polymers had hydrodynamic
      diameters of 68 nm for T1 (75 MUM) in acetonitrile and 105 nm for T2 (75 MUM) in
      water/acetonitrile (1:1). The 3D spherical structures of the supramolecular
      polymers formed in different solvents were also supported by SEM and AFM
      experiments. 

PMID- 24302552
TI  - Development of fore- and hindlimb muscles in GFP-transgenic axolotls:
      morphogenesis, the tetrapod bauplan, and new insights on the forelimb-hindlimb
      enigma.
AB  - The axolotl is becoming one of the most used model organisms in developmental and
      regenerative studies but no publication has described in detail the development
      of its forelimb and hindlimb muscles. We describe and illustrate the ontogeny of
      these muscles in transgenic axolotls that express GFP in muscle fibers and
      discuss our results and data previously obtained by us and by other authors about
      limb regeneration in axolotls and ontogeny in frogs and other tetrapods. Our
      observations and comparisons: (1) demonstrate radio-ulnar and ventro-dorsal
      morphogenetic gradients in the order of axolotl forelimb muscle formation and
      differentiation, while in axolotl hindlimb ontogeny there are only proximo-distal
      and tibio-fibular gradients; some of the axolotl gradients are therefore
      different from the ulno-radial/fibulo-tibial fore- and hindlimb and the dorso
      ventral hindimb ontogenetic morphogenetic gradients seen in frogs and amniotes
      such as chickens; (2) provide a potential explanation for the usual presence, in
      both limbs of taxa from all major tetrapod groups, of more radial/tibial muscles
      than ulnar/fibular muscles; (3) support the "in-out" developmental mechanism of
      appendicular muscle formation; (4) offer new insights about the ancestral Bauplan
      of tetrapod limbs, including the striking similarity of the zeugopodial
      (forearm/leg) and autopodial (hand/foot) muscles of the two limbs and the ventro
      dorsal symmetry of the zeugopodial muscles of a same limb; and (5) provide
      further evidence to corroborate the hypothesis that these similarities are due to
      derived homoplastic events that occurred during the fins-limbs transition and not
      due to forelimb-hindlimb serial homology.

PMID- 24302553
TI  - Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133
      modify susceptibility to and survival of gastric cancer.
AB  - CD133 is one of the most common stem cell markers, and functional single
      nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus
      cancer risk and patient survival. We hypothesized that potentially functional
      CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test
      this hypothesis, we conducted a case-control study of 371 GC patients and 313
      cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped
      four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G,
      rs10022537T>A, and rs3130C>T) and used logistic regression analysis for
      associations of these SNPs with GC risk and Cox hazards regression analysis for
      survival. We found that compared with the miRNA binding site rs2240688 AA
      genotype, AC + CC genotypes were associated with significantly increased GC risk
      (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site
      rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk
      (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all
      patients, the risk rs3130 TT variant genotype was significantly associated with
      overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and
      recessive models, respectively). These findings suggest that these two CD133
      miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers
      for genetic susceptibility to GC and possible predictors for survival in GC
      patients but require further validation by larger studies.

PMID- 24302554
TI  - Testing the direct, indirect, and moderated effects of childhood animal cruelty
      on future aggressive and non-aggressive offending.
AB  - The relationship between childhood cruelty toward animals and subsequent
      aggressive offending was explored in 1,336 (1,154 male, 182 female) participants
      from the 11-wave Pathways to Desistance study (Mulvey, 2013). Aggressive and
      income offending at Waves 1 through 10 were regressed onto a dichotomous measure
      of prior involvement in animal cruelty and four control variables (age, race,
      sex, early onset behavior problems) assessed at Wave 0 (baseline). Results
      indicated that childhood animal cruelty was equally predictive of aggressive and
      non-aggressive (income) offending, a finding inconsistent with the hypothesis
      that cruelty toward animals desensitizes a person to future interpersonal
      aggression or in some way prepares the individual for interpersonal violence
      toward humans. Whereas a significant sex by animal cruelty interaction was
      predicted, there was no evidence that sex or any of the other demographic
      variables included in this study (age, race) consistently moderated the animal
      cruelty-subsequent offending relationship. On the other hand, two cognitive
      personality measures (interpersonal hostility, callousness/unemotionality) were
      found to successfully mediate the animal cruelty-subsequent offending
      relationship. Outcomes from this study imply that a causal nexus-partially or
      fully mediated by hostility, callousness/unemotionality, and other cognitive
      personality variables-may exist between childhood animal cruelty and subsequent
      offending, although the effect is not specific to violence.

PMID- 24302555
TI  - Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent
      proliferation.
AB  - Tumors showing evidence of epithelial-to-mesenchymal transition (EMT) have been
      associated with metastasis, drug resistance, and poor prognosis. Heterogeneity
      along the EMT spectrum is observed between and within tumors. To develop
      effective therapeutics, a mechanistic understanding of how EMT affects the
      molecular requirements for proliferation is needed. We found that although cells
      use phosphoinositide 3-kinase (PI3K) for proliferation in both the epithelial and
      mesenchymal states, EMT rewires the mechanism of PI3K pathway activation. In
      epithelial cells, autocrine ERBB3 activation maintains PI3K signaling, whereas
      after EMT, downregulation of ERBB3 disrupts autocrine signaling to PI3K. Loss of
      ERBB3 leads to reduced serum-independent proliferation after EMT that can be
      rescued through reactivation of PI3K by enhanced signaling from p110alpha, ERBB3
      reexpression, or growth factor stimulation. In vivo, we demonstrate that PIK3CA
      expression is upregulated in mesenchymal tumors with low levels of ERBB3. This
      study defines how ERBB3 downregulation after EMT affects PI3K-dependent
      proliferation. SIGNIFICANCE: This study describes a mechanism through which EMT
      transition alters the proliferative potential of cells by modulating ERBB3
      expression. Furthermore, it demonstrates the potential for multiple molecular
      routes to drive proliferation in different cell states, illustrating how changes
      in EMT status can rewire signaling upstream of cell proliferation.

PMID- 24302556
TI  - Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified
      FGFR1 in lung cancer.
AB  - The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently
      amplified in squamous cell lung cancer. However, it is currently unknown which of
      the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor
      (FGFR) inhibition. We found that, in contrast with other recurrent
      amplifications, the 8p12 region included multiple centers of amplification,
      suggesting marked genomic heterogeneity. FGFR1-amplified tumor cells were
      dependent on FGFR ligands in vitro and in vivo. Furthermore, ectopic expression
      of FGFR1 was oncogenic, which was enhanced by expression of MYC. We found that
      MYC was coexpressed in 40% of FGFR1-amplified tumors. Tumor cells coexpressing
      MYC were more sensitive to FGFR inhibition, suggesting that patients with FGFR1
      amplified and MYC-overexpressing tumors may benefit from FGFR inhibitor therapy.
      Thus, both cell-autonomous and non-cell-autonomous mechanisms of transformation
      modulate FGFR dependency in FGFR1-amplified lung cancer, which may have
      implications for patient selection for treatment with FGFR inhibitors.
      SIGNIFICANCE: Amplification of FGFR1 is one of the most frequent candidate
      targets in lung cancer. Here, we show that multiple factors affect the
      tumorigenic potential of FGFR1, thus providing clinical hypotheses for refinement
      of patient selection.

PMID- 24302557
TI  - Effect of the surface chemistry of insulin fibrils on the aggregation rate.
AB  - Structure transition cascade: Insulin fibrils undergo a secondary structural
      transition-from the alpha-rich to the beta-rich form-upon progressively
      increasing the incubation time from 0.5 to ten hours. Atomic force microscopy
      measurements show that the fibril surface chemistry changes from hydrophilic to
      hydrophobic and the aggregation rate increases fivefold. 

PMID- 24302558
TI  - Fresh onion juice enhanced copulatory behavior in male rats with and without
      paroxetine-induced sexual dysfunction.
AB  - Onion (Allium cepa) is one of the most commonly cultivated species of the family
      Liliaceae, and has long been used in dietary and therapeutic applications.
      Treatment with fresh onion juice has been reported to promote testosterone
      production in male rats. Testosterone is the male sex hormone responsible for
      enhancing sexual libido and potency. This study aimed to investigate the effects
      of onion juice on copulatory behavior of sexually potent male rats and in male
      rats with paroxetine-induced sexual dysfunction. Sexually experienced male rats
      were divided into seven groups: a control group, three onion juice-treated
      groups, a paroxetine-treated group, and two groups treated with paroxetine plus
      different doses of onion juice. At the end of the treatments, sexual behavior
      parameters and testosterone levels were measured and compared among the groups.
      Administration of onion juice significantly reduced mount frequency and latency
      and increased the copulatory efficacy of potent male rats. In addition,
      administration of onion juice attenuated the prolonged ejaculatory latency period
      induced by paroxetine and increased the percentage of ejaculating rats. Serum
      testosterone levels increased significantly by onion juice administration.
      However, a significant reduction in testosterone because of paroxetine therapy
      was observed. This reduction was restored to normal levels by administration of
      onion juice. This study conclusively demonstrates that fresh onion juice improves
      copulatory behavior in sexually potent male rats and in those with paroxetine
      induced sexual dysfunction by increasing serum testosterone levels. 

PMID- 24302559
TI  - Optical imaging of mitochondrial redox state in rodent models with 3
      iodothyronamine.
AB  - This study used an optical technique to measure the effects of treating low (10
      mg/kg) and high (25 mg/kg) doses of 3-iodothyronamine (T1AM) on the metabolism in
      the kidney and heart of mice. The ratio of two intrinsic fluorophores in tissue,
      (NADH/FAD), called the NADH redox ratio (NADH RR), is a marker of the metabolic
      state of the tissue. A cryofluorescence imaging instrument was used to provide a
      quantitative assessment of NADH RR in both kidneys and hearts in mice treated
      with 3-iodothyronamine. We compared those results to corresponding tissues in
      control mice. In the kidneys of mice treated with a high dose T1AM, the mean
      values of the maximum projection of NADH RR were 2.6 +/- 0.6 compared to 3.20 +/-
      0.03 in control mice, indicating a 19% (+/- 0.4) significant increase in
      oxidative stress (OS) in the high dose-treated kidneys (P = 0.047). However,
      kidneys treated with a low dose of T1AM showed no difference in NADH RR compared
      to the kidneys of control mice. Furthermore, low versus high dose treatment of
      T1AM showed different responses in the heart than in the kidneys. The mean value
      of the maximum projection of NADH RR in the heart changed from 3.0 +/- 0.3 to 3.2
      +/- 0.6 for the low dose and the high dose T1AM-treated mice, respectively, as
      compared to 2.8 +/- 0.7 in control mice. These values correspond to a 9% (+/-0.5)
      (P = 0.045) and 14% (+/-0.5) (P = 0.008) significant increase in NADH RR in the
      T1AM-treated hearts, indicating that the high dose T1AM-treated tissues have
      reduced OS compared to the low dose-treated tissues or the control tissues. These
      results suggest that while T1AM at a high dose increases oxidative response in
      kidneys, it has a protective effect in the heart and may exert its effect through
      alternative pathways at different doses and at tissue specific levels.

PMID- 24302562
TI  - Profiling and characterization of sialylated N-glycans by 2D-HPLC (HIAX/PGC) with
      online orbitrap MS/MS and offline MSn.
AB  - Glycosylation is a critical parameter used to evaluate protein quality and
      consistency. N-linked glycan profiling is fundamental to the support of
      biotherapeutic protein manufacturing from early stage process development through
      drug product commercialization. Sialylated glycans impact the serum half-life of
      receptor-Fc fusion proteins (RFPs), making their quality and consistency a
      concern during the production of fusion proteins. Here, we describe an analytical
      approach providing both quantitative profiling and in-depth mass spectrometry
      (MS)-based structural characterization of sialylated RFP N-glycans. Aiming to
      efficiently link routine comparability studies with detailed structural
      characterization, an integrated workflow was implemented employing fluorescence
      detection, online positive and negative ion tandem mass spectrometry (MS/MS), and
      offline static nanospray ionization-sequential mass spectrometry (NSI-MS(n)). For
      routine use, high-performance liquid chromatography profiling employs established
      fluorescence detection of 2-aminobenzoic acid derivatives (2AA) and hydrophilic
      interaction anion-exchange chromatography (HIAX) charge class separation. Further
      characterization of HIAX peak fractions is achieved by online (-) ion orbitrap
      MS/MS, offering the advantages of high mass accuracy and data-dependent MS/MS. As
      required, additional characterization uses porous graphitized carbon in the
      second chromatographic dimension to provide orthogonal (+) ion MS/MS spectra and
      buffer-free liquid chromatography peak eluants that are optimum for offline (+)/(
      ) NSI-MS(n) investigations to characterize low-abundance species and specific
      moieties including O-acetylation and sulfation.

PMID- 24302563
TI  - Base-catalyzed tandem Michael/dehydro-Diels-Alder reaction of alpha,alpha
      dicyanoolefins with electron-deficient 1,3-conjugated enynes: a facile entry to
      angularly fused polycycles.
AB  - Angularly fused carbocyclic frameworks and their heteroatom-substituted analogues
      exist in many natural products that display a broad and interesting range of
      biological activities. Preparation of polycyclic products by cycloaddition
      reactions have been the long-standing hot topic in the synthetic community.
      Dehydro-Diels-Alder (DDA) reactions are one class of dehydropericyclic reactions
      that are derived conceptually by systematic removal of hydrogen atom pairs. A
      base-promoted tandem Michael addition and DDA reaction of alpha,alpha
      dicyanoolefins with electron-deficient 1,3-conjugated enynes was realized in
      which a DDA reaction takes place between the arylalkynes and electron-deficient
      tetrasubstituted olefin. The control experiments support the stepwise anionic
      reaction pathway rather than the concerted reaction pathway. 

PMID- 24302561
TI  - Morphine regulates expression of MU-opioid receptor MOR-1A, an intron-retention
      carboxyl terminal splice variant of the MU-opioid receptor (OPRM1) gene via miR
      103/miR-107.
AB  - The MU-opioid receptor (MOR-1) gene OPRM1 undergoes extensive alternative
      splicing, generating an array of splice variants. Of these variants, MOR-1A, an
      intron-retention carboxyl terminal splice variant identical to MOR-1 except for
      the terminal intracellular tail encoded by exon 3b, is quite abundant and
      conserved from rodent to humans. Increasing evidence indicates that miroRNAs
      (miRNAs) regulate MOR-1 expression and that MU agonists such as morphine modulate
      miRNA expression. However, little is known about miRNA regulation of the OPRM1
      splice variants. Using 3'-rapid amplification cDNA end and Northern blot
      analyses, we identified the complete 3'-untranslated region (3'-UTR) for both
      mouse and human MOR-1A and their conserved polyadenylation site, and defined the
      role the 3'-UTR in mRNA stability using a luciferase reporter assay. Computer
      models predicted a conserved miR-103/107 targeting site in the 3'-UTR of both
      mouse and human MOR-1A. The functional relevance of miR-103/107 in regulating
      expression of MOR-1A protein through the consensus miR-103/107 binding sites in
      the 3'-UTR was established by using mutagenesis and a miR-107 inhibitor in
      transfected human embryonic kidney 293 cells and Be(2)C cells that endogenously
      express human MOR-1A. Chronic morphine treatment significantly upregulated miR
      103 and miR-107 levels, leading to downregulation of polyribosome-associated MOR
      1A in both Be(2)C cells and the striatum of a morphine-tolerant mouse, providing
      a new perspective on understanding the roles of miRNAs and OPRM1 splice variants
      in modulating the complex actions of morphine in animals and humans. 

PMID- 24302560
TI  - Activators of G protein signaling exhibit broad functionality and define a
      distinct core signaling triad.
AB  - Activators of G protein signaling (AGS), initially discovered in the search for
      receptor-independent activators of G protein signaling, define a broad panel of
      biologic regulators that influence signal transfer from receptor to G-protein,
      guanine nucleotide binding and hydrolysis, G protein subunit interactions, and/or
      serve as alternative binding partners for Galpha and Gbetagamma independently of
      the classic heterotrimeric Galphabetagamma. AGS proteins generally fall into
      three groups based upon their interaction with and regulation of G protein
      subunits: group I, guanine nucleotide exchange factors (GEF); group II, guanine
      nucleotide dissociation inhibitors; and group III, entities that bind to
      Gbetagamma. Group I AGS proteins can engage all subclasses of G proteins, whereas
      group II AGS proteins primarily engage the Gi/Go/transducin family of G proteins.
      A fourth group of AGS proteins with selectivity for Galpha16 may be defined by
      the Mitf-Tfe family of transcription factors. Groups I-III may act in concert,
      generating a core signaling triad analogous to the core triad for heterotrimeric
      G proteins (GEF + G proteins + effector). These two core triads may function
      independently of each other or actually cross-integrate for additional signal
      processing. AGS proteins have broad functional roles, and their discovery has
      advanced new concepts in signal processing, cell and tissue biology, receptor
      pharmacology, and system adaptation, providing unexpected platforms for
      therapeutic and diagnostic development. 

PMID- 24302564
TI  - Monocytes, but not T cells, respond to insulin with Akt(S473) phosphorylation
      independent of the donor glucometabolic state.
AB  - BACKGROUND: Obesity is associated with insulin resistance and chronic low-grade
      inflammation. Insulin has been described to have anti-inflammatory effects in
      immune cells. Therefore, insulin resistance in immune cells can be expected to
      have important consequences for immune function. Here, we investigate whether
      freshly isolated monocytes and T cells, isolated from study subjects with a
      normal or disturbed glucometabolic state, respond to insulin with phosphorylation
      of Akt, a key molecule in the insulin signalling pathway. METHODS: A total of 25
      study subjects were enrolled in the study. An oral glucose tolerance test (OGTT)
      was performed, and from fasting insulin and glucose, the homeostasis model
      assessment of insulin resistance (HOMA-IR) index was calculated. Peripheral blood
      mononuclear cells were isolated from heparinized blood and phenotypically
      characterized by flow cytometry. Basal and insulin-induced fractions of
      pAkt(S473)-positive monocytes and T cells were determined by Phosflow. RESULTS:
      On the basis of the OGTT, 11 subjects were classified as normal glucose tolerant
      (NGT), 9 had an impaired glucose metabolism (IGM) and 5 had type 2 diabetes
      (T2DM). The fraction of pAkt(S473)positive-T cells and monocytes, in the absence
      of insulin, was low in all subjects. Incubation with insulin did not induce Akt
      phosphorylation in CD4+ and CD8+ T cells in normal subjects. However, in the
      monocyte fraction, an insulin-dose-dependent increase of the pAkt(S473)positive
      cell fraction was observed. This response did not differ between NGT, IGM and
      T2DM and was not correlated with HOMA-IR. CONCLUSIONS: In this study, we show
      that freshly isolated monocytes, but not T cells, are insulin-sensitive cells and
      that this insulin sensitivity of monocytes is not negatively affected by the
      glucometabolic state of the donor.

PMID- 24302566
TI  - Rhodium-catalyzed intramolecular hydroarylation of 1-halo-1-alkynes:
      regioselective synthesis of semihydrogenated aromatic heterocycles.
AB  - The regioselective intramolecular hydroarylation of (3-halo-2-propynyl)anilines,
      (3-halo-2-propynyl) aryl ethers, or (4-halo-3-butynyl) aryl ethers was
      efficiently catalyzed by Rh2(OCOCF3)4 to give semihydrogenated aromatic
      heterocycles, such as 4-halo-1,2-dihydroquinolines, 4-halo-3-chromenes, or 4
      (halomethylene)chromans, in good to excellent yields. Some synthetic applications
      taking advantage of the halo-substituents of the products are also illustrated.

PMID- 24302565
TI  - Consequences of germline variation disrupting the constitutional translational
      initiation codon start sites of MLH1 and BRCA2: Use of potential alternative
      start sites and implications for predicting variant pathogenicity.
AB  - Variants that disrupt the translation initiation sequences in cancer
      predisposition genes are generally assumed to be deleterious. However, few
      studies have validated these assumptions with functional and clinical data. Two
      cancer syndrome gene variants likely to affect native translation initiation were
      identified by clinical genetic testing: MLH1:c.1A>G p.(Met1?) and
      BRCA2:c.67+3A>G. In vitro GFP-reporter assays were conducted to assess the
      consequences of translation initiation disruption on alternative downstream
      initiation codon usage. Analysis of MLH1:c.1A>G p.(Met1?) showed that translation
      was mostly initiated at an in-frame position 103 nucleotides downstream, but also
      at two ATG sequences downstream. The protein product encoded by the in-frame
      transcript initiating from position c.103 showed loss of in vitro mismatch repair
      activity comparable to known pathogenic mutations. BRCA2:c.67+3A>G was shown by
      mRNA analysis to result in an aberrantly spliced transcript deleting exon 2 and
      the consensus ATG site. In the absence of exon 2, translation initiated mostly at
      an out-of-frame ATG 323 nucleotides downstream, and to a lesser extent at an in
      frame ATG 370 nucleotides downstream. Initiation from any of the downstream
      alternative sites tested in both genes would lead to loss of protein function,
      but further clinical data is required to confirm if these variants are associated
      with a high cancer risk. Importantly, our results highlight the need for caution
      in interpreting the functional and clinical consequences of variation that leads
      to disruption of the initiation codon, since translation may not necessarily
      occur from the first downstream alternative start site, or from a single
      alternative start site.

PMID- 24302567
TI  - Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds.
AB  - Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver
      disease that is not from excess alcohol consumption, but is often associated with
      obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is
      complicated and involves oxidative stress, lipotoxicity, mitochondrial damage,
      insulin resistance, inflammation, and excessive dietary fat intake, which
      increase hepatic lipid influx and de novo lipogenesis and impair insulin
      signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD.
      Overproduction of proinflammatory adipokines from adipose tissue also affects
      hepatic metabolic function. Current NAFLD therapies are limited; thus, much
      attention has been focused on identification of potential dietary substances from
      fruits, vegetables, and edible plants to provide a new strategy for NAFLD
      treatment. Dietary natural compounds, such as carotenoids, omega-3-PUFAs,
      flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a
      variety of mechanisms to prevent and improve NAFLD. Here, we summarize and
      briefly discuss the currently known targets and signaling pathways as well as the
      role of dietary natural compounds that interfere with NAFLD pathogenesis. 

PMID- 24302568
TI  - ABC transporter functions as a pacemaker for sequestration of plant glucosides in
      leaf beetles.
AB  - Plant-herbivore interactions dominate the planet's terrestrial ecology. When it
      comes to host-plant specialization, insects are among the most versatile
      evolutionary innovators, able to disarm multiple chemical plant defenses.
      Sequestration is a widespread strategy to detoxify noxious metabolites,
      frequently for the insect's own benefit against predation. In this study, we
      describe the broad-spectrum ATP-binding cassette transporter CpMRP of the poplar
      leaf beetle, Chrysomela populi as the first candidate involved in the
      sequestration of phytochemicals in insects. CpMRP acts in the defensive glands of
      the larvae as a pacemaker for the irreversible shuttling of pre-selected
      metabolites from the hemolymph into defensive secretions. Silencing CpMRP in vivo
      creates a defenseless phenotype, indicating its role in the secretion process is
      crucial. In the defensive glands of related leaf beetle species, we identified
      sequences similar to CpMRP and assume therefore that exocrine gland-based
      defensive strategies, evolved by these insects to repel their enemies, rely on
      ABC transporters as a key element. DOI:
      http://dx.doi.org/10.7554/eLife.01096.001. 

PMID- 24302569
TI  - Ribosome profiling reveals pervasive and regulated stop codon readthrough in
      Drosophila melanogaster.
AB  - Ribosomes can read through stop codons in a regulated manner, elongating rather
      than terminating the nascent peptide. Stop codon readthrough is essential to
      diverse viruses, and phylogenetically predicted to occur in a few hundred genes
      in Drosophila melanogaster, but the importance of regulated readthrough in
      eukaryotes remains largely unexplored. Here, we present a ribosome profiling
      assay (deep sequencing of ribosome-protected mRNA fragments) for Drosophila
      melanogaster, and provide the first genome-wide experimental analysis of
      readthrough. Readthrough is far more pervasive than expected: the vast majority
      of readthrough events evolved within D. melanogaster and were not predicted
      phylogenetically. The resulting C-terminal protein extensions show evidence of
      selection, contain functional subcellular localization signals, and their
      readthrough is regulated, arguing for their importance. We further demonstrate
      that readthrough occurs in yeast and humans. Readthrough thus provides general
      mechanisms both to regulate gene expression and function, and to add plasticity
      to the proteome during evolution. DOI: http://dx.doi.org/10.7554/eLife.01179.001.

PMID- 24302570
TI  - Cytoplasmic translocation of the retinoblastoma protein disrupts sarcomeric
      organization.
AB  - Skeletal muscle degeneration is a complication arising from a variety of chronic
      diseases including advanced cancer. Pro-inflammatory cytokine TNF-alpha plays a
      pivotal role in mediating cancer-related skeletal muscle degeneration. Here, we
      show a novel function for retinoblastoma protein (Rb), where Rb causes sarcomeric
      disorganization. In human skeletal muscle myotubes (HSMMs), up-regulation of
      cyclin-dependent kinase 4 (CDK4) and concomitant phosphorylation of Rb was
      induced by TNF-alpha treatment, resulting in the translocation of phosphorylated
      Rb to the cytoplasm. Moreover, induced expression of the nuclear exporting signal
      (NES)-fused form of Rb caused disruption of sarcomeric organization. We
      identified mammalian diaphanous-related formin 1 (mDia1), a potent actin
      nucleation factor, as a binding partner of cytoplasmic Rb and found that mDia1
      helps maintain the structural integrity of the sarcomere. These results reveal a
      novel non-nuclear function for Rb and suggest a potential mechanism of TNF-alpha
      induced disruption of sarcomeric organization. DOI:
      http://dx.doi.org/10.7554/eLife.01228.001. 

PMID- 24302571
TI  - Decoding neural responses to temporal cues for sound localization.
AB  - The activity of sensory neural populations carries information about the
      environment. This may be extracted from neural activity using different
      strategies. In the auditory brainstem, a recent theory proposes that sound
      location in the horizontal plane is decoded from the relative summed activity of
      two populations in each hemisphere, whereas earlier theories hypothesized that
      the location was decoded from the identity of the most active cells. We tested
      the performance of various decoders of neural responses in increasingly complex
      acoustical situations, including spectrum variations, noise, and sound
      diffraction. We demonstrate that there is insufficient information in the pooled
      activity of each hemisphere to estimate sound direction in a reliable way
      consistent with behavior, whereas robust estimates can be obtained from neural
      activity by taking into account the heterogeneous tuning of cells. These
      estimates can still be obtained when only contralateral neural responses are
      used, consistently with unilateral lesion studies. DOI:
      http://dx.doi.org/10.7554/eLife.01312.001. 

PMID- 24302572
TI  - Mechanism of chiral proofreading during translation of the genetic code.
AB  - The biological macromolecular world is homochiral and effective enforcement and
      perpetuation of this homochirality is essential for cell survival. In this study,
      we present the mechanistic basis of a configuration-specific enzyme that
      selectively removes D-amino acids erroneously coupled to tRNAs. The crystal
      structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum
      in complex with a substrate-mimicking analog shows how it uses an invariant
      'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming D
      aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the
      unique side chain-independent mode of substrate recognition provides a clear
      explanation for DTD's ability to act on multiple D-amino acids. The strict chiral
      specificity elegantly explains how the enriched cellular pool of L-aminoacyl
      tRNAs escapes this proofreading step. The study thus provides insights into a
      fundamental enantioselection process and elucidates a chiral enforcement
      mechanism with a crucial role in preventing D-amino acid infiltration during the
      evolution of translational apparatus. DOI:
      http://dx.doi.org/10.7554/eLife.01519.001. 

PMID- 24302574
TI  - A novel site comes into sight.
AB  - Oxysterols modulate the Hedgehog signalling pathway by binding a novel site on
      the membrane protein Smoothened, which may offer new options for the treatment of
      cancers linked to this pathway. 

PMID- 24302573
TI  - Hdac6 regulates Tip60-p400 function in stem cells.
AB  - In embryonic stem cells (ESCs), the Tip60 histone acetyltransferase activates
      genes required for proliferation and silences genes that promote differentiation.
      Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60
      p400 complex from ESCs. Hdac6 is necessary for regulation of most Tip60-p400
      target genes, particularly those repressed by the complex. Unlike differentiated
      cells, where Hdac6 is mainly cytoplasmic, Hdac6 is largely nuclear in ESCs,
      neural stem cells (NSCs), and some cancer cell lines, and interacts with Tip60
      p400 in each. Hdac6 localizes to promoters bound by Tip60-p400 in ESCs, binding
      downstream of transcription start sites. Surprisingly, Hdac6 does not appear to
      deacetylate histones, but rather is required for Tip60-p400 binding to many of
      its target genes. Finally, we find that, like canonical subunits of Tip60-p400,
      Hdac6 is necessary for robust ESC differentiation. These data suggest that Hdac6
      plays a major role in the modulation of Tip60-p400 function in stem cells. DOI:
      http://dx.doi.org/10.7554/eLife.01557.001. 

PMID- 24302575
TI  - Disruptive influence.
AB  - Cachexia, a condition that kills about one-fifth of cancer patients, may be
      linked to Rb-a protein that is already linked to various cancers-moving from the
      cell nucleus to the cytoplasm. 

PMID- 24302577
TI  - topPTM: a new module of dbPTM for identifying functional post-translational
      modifications in transmembrane proteins.
AB  - Transmembrane (TM) proteins have crucial roles in various cellular processes. The
      location of post-translational modifications (PTMs) on TM proteins is associated
      with their functional roles in various cellular processes. Given the importance
      of PTMs in the functioning of TM proteins, this study developed topPTM (available
      online at http://topPTM.cse.yzu.edu.tw), a new dbPTM module that provides a
      public resource for identifying the functional PTM sites on TM proteins with
      structural topology. Experimentally verified TM topology data were integrated
      from TMPad, TOPDB, PDBTM and OPM. In addition to the PTMs obtained from dbPTM,
      experimentally verified PTM sites were manually extracted from research articles
      by text mining. In an attempt to provide a full investigation of PTM sites on TM
      proteins, all UniProtKB protein entries containing annotations related to
      membrane localization and TM topology were considered potential TM proteins. Two
      effective tools were then used to annotate the structural topology of the
      potential TM proteins. The TM topology of TM proteins is represented by graphical
      visualization, as well as by the PTM sites. To delineate the structural
      correlation between the PTM sites and TM topologies, the tertiary structure of
      PTM sites on TM proteins was visualized by Jmol program. Given the support of
      research articles by manual curation and the investigation of domain-domain
      interactions in Protein Data Bank, 1347 PTM substrate sites are associated with
      protein-protein interactions for 773 TM proteins. The database content is
      regularly updated on publication of new data by continuous surveys of research
      articles and available resources. 

PMID- 24302579
TI  - DPRP: a database of phenotype-specific regulatory programs derived from
      transcription factor binding data.
AB  - Gene expression profiling has been extensively used in the past decades,
      resulting in an enormous amount of expression data available in public databases.
      These data sets are informative in elucidating transcriptional regulation of
      genes underlying various biological and clinical conditions. However, it is
      usually difficult to identify transcription factors (TFs) responsible for gene
      expression changes directly from their own expression, as TF activity is often
      regulated at the posttranscriptional level. In recent years, technical advances
      have made it possible to systematically determine the target genes of TFs by ChIP
      seq experiments. To identify the regulatory programs underlying gene expression
      profiles, we constructed a database of phenotype-specific regulatory programs
      (DPRP, http://syslab.nchu.edu.tw/DPRP/) derived from the integrative analysis of
      TF binding data and gene expression data. DPRP provides three methods: the
      Fisher's Exact Test, the Kolmogorov-Smirnov test and the BASE algorithm to
      facilitate the application of gene expression data for generating new hypotheses
      on transcriptional regulatory programs in biological and clinical studies. 

PMID- 24302578
TI  - The complex methylome of the human gastric pathogen Helicobacter pylori.
AB  - The genome of Helicobacter pylori is remarkable for its large number of
      restriction-modification (R-M) systems, and strain-specific diversity in R-M
      systems has been suggested to limit natural transformation, the major driving
      force of genetic diversification in H. pylori. We have determined the
      comprehensive methylomes of two H. pylori strains at single base resolution,
      using Single Molecule Real-Time (SMRT(r)) sequencing. For strains 26695 and J99
      R3, 17 and 22 methylated sequence motifs were identified, respectively. For most
      motifs, almost all sites occurring in the genome were detected as methylated.
      Twelve novel methylation patterns corresponding to nine recognition sequences
      were detected (26695, 3; J99-R3, 6). Functional inactivation, correction of
      frameshifts as well as cloning and expression of candidate methyltransferases
      (MTases) permitted not only the functional characterization of multiple, yet
      undescribed, MTases, but also revealed novel features of both Type I and Type II
      R-M systems, including frameshift-mediated changes of sequence specificity and
      the interaction of one MTase with two alternative specificity subunits resulting
      in different methylation patterns. The methylomes of these well-characterized H.
      pylori strains will provide a valuable resource for future studies investigating
      the role of H. pylori R-M systems in limiting transformation as well as in gene
      regulation and host interaction. 

PMID- 24302580
TI  - CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into
      tumors upon chemotherapy.
AB  - The therapeutic efficacy of anthracyclines relies, at least partially, on the
      induction of a dendritic cell- and T-lymphocyte-dependent anticancer immune
      response. Here, we show that anthracycline-based chemotherapy promotes the
      recruitment of functional CD11b(+)CD11c(+)Ly6C(high)Ly6G(-)MHCII(+) dendritic
      cell-like antigen-presenting cells (APC) into the tumor bed, but not into
      lymphoid organs. Accordingly, draining lymph nodes turned out to be dispensable
      for the proliferation of tumor antigen-specific T cells within neoplastic lesions
      as induced by anthracyclines. In addition, we found that tumors treated with
      anthracyclines manifest increased expression levels of the chemokine Ccl2. Such a
      response is important as neoplasms growing in Ccl2(-/-) mice failed to accumulate
      dendritic cell-like APCs in response to chemotherapy. Moreover, cancers
      developing in mice lacking Ccl2 or its receptor (Ccr2) exhibited suboptimal
      therapeutic responses to anthracycline-based chemotherapy. Altogether, our
      results underscore the importance of the CCL2/CCR2 signaling axis for therapeutic
      anticancer immune responses as elicited by immunogenic chemotherapy.

PMID- 24302582
TI  - Adenosine-to-inosine RNA editing mediated by ADARs in esophageal squamous cell
      carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC), the major histologic form of
      esophageal cancer, is a heterogeneous tumor displaying a complex variety of
      genetic and epigenetic changes. Aberrant RNA editing of adenosine-to-inosine (A
      to-I), as it is catalyzed by adenosine deaminases acting on RNA (ADAR),
      represents a common posttranscriptional modification in certain human diseases.
      In this study, we investigated the status and role of ADARs and altered A-to-I
      RNA editing in ESCC tumorigenesis. Among the three ADAR enzymes expressed in
      human cells, only ADAR1 was overexpressed in primary ESCC tumors. ADAR1
      overexpression was due to gene amplification. Patients with ESCC with tumoral
      overexpression of ADAR1 displayed a poor prognosis. In vitro and in vivo
      functional assays established that ADAR1 functions as an oncogene during ESCC
      progression. Differential expression of ADAR1 resulted in altered gene-specific
      editing activities, as reflected by hyperediting of FLNB and AZIN1 messages in
      primary ESCC. Notably, the edited form of AZIN1 conferred a gain-of-function
      phenotype associated with aggressive tumor behavior. Our findings reveal that
      altered gene-specific A-to-I editing events mediated by ADAR1 drive the
      development of ESCC, with potential implications in diagnosis, prognosis, and
      treatment of this disease.

PMID- 24302581
TI  - PPARalpha activation can help prevent and treat non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) not amenable to surgical resection has a high
      mortality rate, due to the ineffectiveness and toxicity of chemotherapy. Thus,
      there remains an urgent need of efficacious drugs that can combat this disease.
      In this study, we show that targeting the formation of proangiogenic
      epoxyeicosatrienoic acids (EET) by the cytochrome P450 arachidonic acid
      epoxygenases (Cyp2c) represents a new and safe mechanism to treat NSCLC growth
      and progression. In the transgenic murine K-Ras model and human orthotopic models
      of NSCLC, we found that Cyp2c44 could be downregulated by activating the
      transcription factor PPARalpha with the ligands bezafibrate and Wyeth-14,643.
      Notably, both treatments reduced primary and metastatic NSCLC growth, tumor
      angiogenesis, endothelial Cyp2c44 expression, and circulating EET levels. These
      beneficial effects were independent of the time of administration, whether before
      or after the onset of primary NSCLC, and they persisted after drug withdrawal,
      suggesting the benefits were durable. Our findings suggest that strategies to
      downregulate Cyp2c expression and/or its enzymatic activity may provide a safer
      and effective strategy to treat NSCLC. Moreover, as bezafibrate is a well
      tolerated clinically approved drug used for managing lipidemia, our findings
      provide an immediate cue for clinical studies to evaluate the utility of
      PPARalpha ligands as safe agents for the treatment of lung cancer in humans.

PMID- 24302584
TI  - Lipid-modifying enzymes in human tear fluid and corneal epithelial stress
      response.
AB  - PURPOSE: Since homeostasis at the ocular surface requires a delicate balance
      between numerous factors, and the external environment contributes as an
      unpredictable component, we aimed to understand the role that various lipids and
      their regulators have in the complex process that maintains a healthy corneal
      surface. METHODS: Through basic proteomics, we tested the presence of
      sphingolipid metabolism enzymes in normal human tears, and then used a cell
      culture model to study how the proteins are secreted and for what purpose.
      RESULTS: When studying healthy tears, we found that sphingolipid-specific
      enzymes, acid and neutral sphingomyelinases, and ceramidases can be detected. The
      role played by sphingolipid metabolism in stress provided the motivation for
      further studies concerning their secretion/leakage in the extracellular
      environment in a cell culture model of human corneal epithelial cells (HCE).
      Among the stress agents investigated (i.e., ultraviolet B [UV-B] radiation,
      hyperosmolarity [HO], and lipopolysaccharide [LPS]), UV-B and HO induced dose
      dependent release/secretion of sphingomyelinases from the cells. In an attempt to
      identify the route of secretion or release of the enzyme, we discovered that the
      tested stress stimuli induced shedding of extracellular vesicles in the HCE
      conditioned medium. CONCLUSIONS: Extracellular stress affects tear fluid
      composition more profoundly than just secretion of proinflammatory mediators.
      Lipids at the ocular surface, either in tear fluid or within the corneal
      epithelial cells, can be modified by a relatively large array of lipases to
      modulate their functions. Moreover, extracellular vesicles in the tear fluid
      could represent a valuable noninvasive diagnosis tool for anterior segment
      diseases.

PMID- 24302583
TI  - Daily insulin doses and injection frequencies of neutral protamine hagedorn (NPH)
      insulin, insulin detemir and insulin glargine in type 1 and type 2 diabetes: a
      multicenter analysis of 51 964 patients from the German/Austrian DPV-wiss
      database.
AB  - BACKGROUND: We performed a comparative analysis of the use of long-acting insulin
      (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla),
      and quantified injection frequencies and daily insulin doses in patients with
      type 1 and 2 diabetes in daily practice. METHODS: A total number of 51 964
      patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with
      exclusive insulin therapy were retrospectively analysed. RESULTS: A total number
      of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and
      38.0%/17.4% Gla, with similar glycaemic control and proportion of severe
      hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean
      proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes
      (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia
      5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of
      NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin
      injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses
      were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla
      (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2
      diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det
      and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean
      daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29
      IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg
      (Det) and 0.67 IU/kg (Gla). CONCLUSIONS: In a 'real-world' setting, the injection
      frequencies and doses of basal and total insulin per day are lowest with the use
      of insulin glargine compared with NPH-insulin or insulin detemir at similar
      glycaemic control and rates of severe hypoglycaemia.

PMID- 24302585
TI  - In vivo lamina cribrosa micro-architecture in healthy and glaucomatous eyes as
      assessed by optical coherence tomography.
AB  - PURPOSE: The lamina cribrosa (LC) is a prime location of glaucomatous damage. The
      purpose of this study was to compare LC 3-dimensional micro-architecture between
      healthy and glaucomatous eyes in vivo by using optical coherence tomography
      (OCT). METHODS: Sixty-eight eyes (19 healthy and 49 glaucomatous) from 47
      subjects were scanned in a 3.5 * 3.5 * 3.64-mm volume (400 * 400 * 896 pixels) at
      the optic nerve head by using swept-source OCT. The LC micro-architecture
      parameters were measured on the visible LC by an automated segmentation
      algorithm. The LC parameters were compared to diagnosis and visual field mean
      deviation (VF MD) by using a linear mixed effects model accounting for age.
      RESULTS: The average VF MD for the healthy and glaucomatous eyes was -0.50 +/-
      0.80 dB and -7.84 +/- 8.75 dB, respectively. Beam thickness to pore diameter
      ratio (P = 0.04) and pore diameter standard deviation (P < 0.01) were increased
      in glaucomatous eyes. With worse MD, beam thickness to pore diameter ratio (P <
      0.01), pore diameter standard deviation (P = 0.05), and beam thickness (P < 0.01)
      showed a statistically significant increase while pore diameter (P = 0.02) showed
      a significant decrease. There were no significant interactions between any of the
      parameters and age (all P > 0.05). CONCLUSIONS: Glaucomatous micro-architecture
      changes in the LC, detected by OCT analysis, reflect beams remodeling and axonal
      loss leading to reduction in pore size and increased pore size variability.

PMID- 24302586
TI  - Thrombin induces epithelial-mesenchymal transition and collagen production by
      retinal pigment epithelial cells via autocrine PDGF-receptor signaling.
AB  - PURPOSE: De-differentiation of RPE cells into mesenchymal cells (epithelial
      mesenchymal transition; EMT) and associated collagen production contributes to
      development of proliferative vitreoretinopathy (PVR). In patients with PVR,
      intraocular coagulation cascade activation occurs and may play an important
      initiating role. Therefore, we examined the effect of the coagulation proteins
      factor Xa and thrombin on EMT and collagen production by RPE cells. METHODS:
      Retinal pigment epithelial cells were stimulated with factor Xa or thrombin and
      the effect on zonula occludens (ZO)-1, alpha-smooth muscle actin (alpha-SMA),
      collagen, and platelet-derived growth factor (PDGF)-B were determined by real
      time quantitative-polymerase chain reaction (RQ-PCR), immunofluorescence
      microscopy, and HPLC and ELISA for collagen and PDGF-BB in culture supernatants,
      respectively. PDGF-receptor activation was determined by phosphorylation analysis
      and inhibition studies using the PDGF-receptor tyrosine kinase inhibitor AG1296.
      RESULTS: Thrombin reduced ZO-1 gene expression (P < 0.05) and enhanced expression
      of the genes encoding alpha-SMA and the pro-alpha1 chain of collagen type-1 (P <
      0.05), indicating EMT. Also, ZO-1 protein expression declined on thrombin
      stimulation, whereas production of alpha-SMA and collagen increased. In contrast
      to thrombin, factor Xa hardly stimulated EMT by RPE. Thrombin clearly induced
      PDGF-BB production and PDGF-Rbeta chain phosphorylation in RPE. Moreover, AG1296
      significantly blocked the effect of thrombin on EMT and collagen production.
      CONCLUSIONS: Our findings demonstrate that thrombin is a potent inducer of EMT by
      RPE via autocrine activation of PDGF-receptor signaling. Coagulation cascade
      induced EMT of RPE may thus contribute to the formation of fibrotic retinal
      membranes in PVR and should be considered as treatment target in PVR.

PMID- 24302587
TI  - Is the association between smoking and the retinal venular diameter reversible
      following smoking cessation?
AB  - PURPOSE: Wider retinal venular caliber is shown to be associated with an
      increased risk of stroke, and smoking is associated with a wider retinal venular
      caliber. However, the impact of smoking cessation on the retinal vessels has not
      been previously reported. We examined this issue in an adult cohort of atomic
      bomb survivors. METHODS: In the Adult Health Study of Japanese atomic bomb
      survivors, 1664 subjects had retinal photographs taken from 2006 to 2008. The
      central retinal artery and vein equivalents (CRAE and CRVE) were calculated using
      a semiautomated software program. Multiple surveys have assessed the effects of
      smoking since 1963. The associations between smoking, the time since cessation,
      and the retinal vessel caliber were determined using linear mixed effects models.
      RESULTS: The CRVE was associated with an increased number of cigarettes smoked
      per day among women after adjusting for potential confounding factors (age, sex,
      blood pressure, hypertensive medications, white blood cell count, diabetes, body
      mass index, lipids, and radiation dose). Females who smoked 10 cigarettes per day
      had a 6.9-MUm wider mean CRVE (P = 0.001) than nonsmokers. Females who had
      stopped smoking for 10 or more years had a mean CRVE similar to those who had
      never smoked (191.8 vs. 194.4 MUm; P = 0.23). These associations were not
      observed in males or for CRAE. CONCLUSIONS: Wider retinal venular caliber is
      associated with smoking in Japanese females; however, this association becomes
      nonsignificant after 10 or more years of smoking cessation, suggesting that the
      impact of smoking on retinal venular dilation is reversible following long-term
      smoking cessation.

PMID- 24302588
TI  - Autoregulation of retinal blood flow in response to decreased ocular perfusion
      pressure in cats: comparison of the effects of increased intraocular pressure and
      systemic hypotension.
AB  - PURPOSE: To investigate the regulatory mechanisms responsible for autoregulation
      of retinal blood flow (RBF) during periods of decreased ocular perfusion pressure
      (OPP). METHODS: The effects of acute reductions in OPP on RBF were assessed using
      laser Doppler velocimetry in cats. The OPP decreased from 90 to 40 mm Hg by
      increasing the IOP (elevated IOP) or by decreasing the systemic blood pressure
      via exsanguination (systemic hypotension). The contributions of nitric oxide
      (NO), adenosine, and/or N-methyl-D-aspartic acid (NMDA) in regulation of the
      retinal arteriolar hemodynamics during decreased OPP was determined at 120
      minutes after intravitreal injection of various inhibitors or PBS. RESULTS:
      Following PBS injection, the flow velocity decreased in proportion to the
      decrease in OPP; however, the retinal arteriolar diameter gradually increased.
      Consequently, the RBF was maintained near baseline levels when the OPP exceeded
      70 mm Hg but decreased significantly (P < 0.01) when the OPP fell to less than or
      equal to 60 mm Hg due to elevated IOP or systemic hypotension. Adenosine receptor
      blocker 8-(p-sulfophenyl)theophylline, significantly (P < 0.01) enhanced
      decreases in RBF induced by elevated IOP and systemic hypotension at OPP from 80
      to 40 mm Hg, whereas NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester and
      NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid only significantly
      (P < 0.01) enhanced reductions in RBF induced by elevated IOP. CONCLUSIONS: These
      results indicate that adenosine contributes to autoregulation of RBF during
      systemic hypotension, whereas adenosine, NO, and NMDA receptors autoregulate the
      RBF after elevated IOP. Different vasoregulatory factors might contribute to
      autoregulation of RBF after decreases in OPP induced by elevated IOP and systemic
      hypotension.

PMID- 24302589
TI  - Characterization of field loss based on microperimetry is predictive of face
      recognition difficulties.
AB  - PURPOSE: To determine how visual field loss as assessed by microperimetry is
      correlated with deficits in face recognition. METHODS: Twelve patients (age
      range, 26-70 years) with impaired visual sensitivity in the central visual field
      caused by a variety of pathologies and 12 normally sighted controls (control
      subject [CS] group; age range, 20-68 years) performed a face recognition task for
      blurred and unblurred faces. For patients, we assessed central visual field loss
      using microperimetry, fixation stability, Pelli-Robson contrast sensitivity, and
      letter acuity. RESULTS: Patients were divided into two groups by microperimetry:
      a low vision (LV) group (n = 8) had impaired sensitivity at the anatomical fovea
      and/or poor fixation stability, whereas a low vision that excluded the fovea
      (LV:F) group (n = 4) was characterized by at least some residual foveal
      sensitivity but insensitivity in other retinal regions. The LV group performed
      worse than the other groups at all blur levels, whereas the performance of the
      LV:F group was not credibly different from that of the CS group. The performance
      of the CS and LV:F groups deteriorated as blur increased, whereas the LV group
      showed consistently poor performance regardless of blur. Visual acuity and
      fixation stability were correlated with face recognition performance.
      CONCLUSIONS: Persons diagnosed as having disease affecting the central visual
      field can recognize faces as well as persons with no visual disease provided that
      they have residual sensitivity in the anatomical fovea and show stable fixation
      patterns. Performance in this task is limited by the upper resolution of
      nonfoveal vision or image blur, whichever is worse.

PMID- 24302591
TI  - Planar and nonplanar free-base tetraarylporphyrins: beta-pyrrole substituents and
      geometric effects on electrochemistry, spectroelectrochemistry, and
      protonation/deprotonation reactions in nonaqueous media.
AB  - A series of planar and nonplanar free-base beta-pyrrole substituted meso
      tetraarylporphyrins were characterized by electrochemistry,
      spectroelectrochemistry, and protonation or deprotonation reactions in neutral,
      acidic, and basic solutions of CH2 Cl2 . The neutral compounds are represented as
      H2 (P), in which P represents a porphyrin dianion with one of several different
      sets of electron-withdrawing or -donating substituents at the messo and/or beta
      pyrrole positions of the macrocycle. The conversion of H2 (P) to [H4 (P)](2+) in
      CH2 Cl2 was accomplished by titration of the neutral porphyrin with
      trifluoroacetic acid (TFA) while the progress of the protonation was monitored by
      UV/Vis spectroscopy, which was also used to calculate logbeta2 for proton
      addition to the core nitrogen atoms of the macrocycle. Cyclic voltammetry was
      performed after each addition of TFA or TBAOH to CH2 Cl2 solutions of the
      porphyrin and half-wave potentials for reduction were evaluated as a function of
      the added acid or base concentration. Thin-layer spectroelectrochemistry was used
      to obtain UV/Vis spectra of the neutral and protonated or deprotonated porphyrins
      under the application of an applied reducing potential. The magnitude of the
      protonation constants, the positions of lambdamax in the UV/Vis spectra and the
      half-wave or peak potentials for reduction are then related to the electronic
      properties of the porphyrin and the data evaluated as a function of the planarity
      or nonplanarity of the porphyrin macrocycle. Surprisingly, the electroreduction
      of the diprotonated nonplanar porphyrins in acid media leads to H2 (P), whereas
      the nonplanar H2 (P) derivatives are reduced to [(P)](2-) in CH2 Cl2 containing
      0.1 M tetra-n-butylammonium perchlorate (TBAP). Thus, in both cases an
      electrochemically initiated deprotonation is observed. 

PMID- 24302590
TI  - Alterations in RD(INK4/ARF) -mediated en bloc regulation of the INK4-ARF locus in
      human squamous cell carcinoma of the head and neck.
AB  - The presence of RD(INK4/ARF) (RD) enhancer in the INK4-ARF locus provides a novel
      mechanism to simultaneously increase the transcription of p15(INK4b) (p15),
      p14ARF (p14), and p16(INK4a) (p16). While such upregulation can be repressed
      through interactions between RD and oncoproteins CDC6 and BMI1, little is known
      about the involvement of RD in cancer. In this study we investigated RD deletions
      in 30 squamous cell carcinoma of the head and neck (SCCHN) and the patient
      matched High At-Risk Mucosa specimens (HARM, "phenotypically normal" tissues
      neighboring SCCHN foci but beyond the surgical resection margin). RD was deleted
      (homozygously/heterozygously) in SCCHN and HARM at the incidence of 36.7% (11/30)
      and 13.3% (4/30), respectively. In comparison, no RD deletion was detected in 26
      oral buccal brush biopsy specimens from healthy donors. Both p16 and p14 were
      lowly expressed in SCCHN and HARM, and their mRNA expression levels were
      positively associated with each other (P < 0.01). Moreover, BMI1 was highly
      expressed in both SCCHN and HARM, and BMI1 overexpression was associated with p16
      downregulation in SCCHN (P < 0.05). These results indicate that RD deletion and
      BMI1 overexpression frequently occur in the early stage of oral carcinogenesis
      and BMI1 overexpression may downregulate the transcription of p16 and p14 through
      interfering with RD.

PMID- 24302592
TI  - Examination of age-dependent effects of fetal ethanol exposure on behavior,
      hippocampal cell counts, and doublecortin immunoreactivity in rats.
AB  - Ethanol is known as a potent teratogen having adverse effects on brain and
      behavior. However, some of the behavioral deficits caused by fetal alcohol
      exposure and well expressed in juveniles ameliorate with maturation may suggest
      some kind of functional recovery occurring during postnatal development. The aim
      of this study was to reexamine age-dependent behavioral impairments in fetal
      alcohol rats and to investigate the changes in neurogenesis and gross morphology
      of the hippocampus during a protracted postnatal period searching for
      developmental deficits and/or delays that would correlate with behavioral
      impairments in juveniles and for potential compensatory processes responsible for
      their amelioration in adults. Ethanol was delivered to the pregnant dams by
      intragastric intubation throughout 7-21 gestation days at daily dose of 6 g/kg.
      Isocaloric intubation and intact control groups were included. Locomotor
      activity, anxiety, and spatial learning tasks were applied to juvenile and young
      adult rats from all groups. Unbiased stereological estimates of hippocampal
      volumes, the total number of pyramidal and granular cells, and double cortin
      expressing neurons were carried out for postnatal days (PDs) PD1, PD10, PD30, and
      PD60. Alcohol insult during second trimester equivalent caused significant
      deficits in the spatial learning in juvenile rats; however, its effect on
      hippocampal morphology was limited to a marginally lower number of granular cells
      in dentate gyrus (DG) on PD30. Thus, initial behavioral deficits and the
      following functional recovery in fetal-alcohol subjects may be due to more subtle
      plastic changes within the hippocampal formation but also in other structures of
      the extended hippocampal circuit. Further investigation is required.

PMID- 24302595
TI  - Parallel fabrication of plasmonic nanocone sensing arrays.
AB  - A fully parallel approach for the fabrication of arrays of metallic nanocones and
      triangular nanopyramids is presented. Different processes utilizing nanosphere
      lithography for the creation of etch masks are developed. Monolayers of spheres
      are reduced in size and directly used as masks, or mono- and double layers are
      employed as templates for the deposition of aluminum oxide masks. The masks are
      transferred into an underlying gold or silver layer by argon ion milling, which
      leads to nanocones or nanopyramids with very sharp tips. Near the tips the
      enhancement of an external electromagnetic field is particularly strong. This
      fact is confirmed by numerical simulations and by luminescence imaging in a
      confocal microscope. Such localized strong fields can amongst others be utilized
      for high-resolution, high-sensitivity spectroscopy and sensing of molecules near
      the tip. Arrays of such plasmonic nanostructures thus constitute controllable
      platforms for surface-enhanced Raman spectroscopy. A thin film of pentacene
      molecules is evaporated onto both nanocone and nanopyramid substrates, and the
      observed Raman enhancement is evaluated. 

PMID- 24302597
TI  - A comparative study of in vitro cytotoxic, antioxidant, and antimicrobial
      activity of Pt(II), Zn(II), Cu(II), and Co(III) complexes with N-heteroaromatic
      Schiff base (E)-2-[N'-(1-pyridin-2-yl-ethylidene)hydrazino]acetate.
AB  - In search for novel biologically active metal based compounds, an evaluation of
      in vitro cytotoxic, antioxidant, and antimicrobial activity of new Pt(II) complex
      and its Zn(II), Cu(II), and Co(III) analogues, with NNO tridentately coordinated
      N-heteroaromatic Schiff base ligand (E)-2-[N'-(1-pyridin-2-yl
      ethylidene)hydrazino]acetate, was performed. Investigation of antioxidative
      properties showed that all of the compounds have strong radical scavenging
      potencies. The Zn(II) complex showed potent inhibition of DNA cleavage by
      hydroxyl radical. A cytotoxic action of investigated compounds was evaluated on
      cultures of human promyelocitic leukaemia (HL-60), human glioma (U251), rat
      glioma (C6), and mouse melanoma (B16) cell lines. It was shown that binuclear
      pentacoordinated Zn(II) complex possesses a strong dose-dependent cytotoxic
      activity, of the same order of magnitude as cisplatin on B16, C6, and U251 cells.
      Furthermore, Zn(II) complex causes oxidative stress-induced apoptotic death of HL
      60 leukemic cells, associated with caspase activation, phosphatidylserine
      externalization, and DNA fragmentation. 

PMID- 24302601
TI  - Batteries: encapsulated monoclinic sulfur for stable cycling of li-s rechargeable
      batteries (adv. Mater. 45/2013).
AB  - On page 6547 Do Kyung Kim, Jang Wook Choi and co-workers describe a highly
      aligned and carbon-encapsulated sulfur cathode synthesized with an AAO template
      that exhibits a high and long cycle life, and the best rate capability based on
      the complete encapsulation of sulfur (physical) and implementation of the
      monoclinic sulfur phase (chemical). 

PMID- 24302596
TI  - GAD-treatment of children and adolescents with recent-onset type 1 diabetes
      preserves residual insulin secretion after 30 months.
AB  - BACKGROUND: This study aimed to analyse data from two different studies (phase II
      and phase III) regarding the safety and efficacy of treatment with alum
      formulated glutamic acid decarboxylase GAD65 (GAD-alum) at 30 months after
      administration to children and adolescents with type 1 diabetes. METHODS: The
      phase II trial was a double-blind, randomised placebo-controlled study, including
      70 children and adolescents who were followed for 30  months. Participants
      received a subcutaneous injection of either 20 ug of GAD-alum or placebo at
      baseline and 1 month later. During a subsequent larger European phase III trial
      including three treatment arms, participants received two or four subcutaneous
      injections of either 20 ug of GAD-alum and/or placebo at baseline, 1, 3 and 9 
      months. The phase III trial was prematurely interrupted at 15 months, but of the
      148 Swedish patients, a majority completed the 21 months follow-up, and 45
      patients completed the trial at 30 months. Both studies included GAD65 auto
      antibodies-positive patients with fasting C-peptide >= 0.10 nmol/l. We have now
      combined the results of these two trials. RESULTS: There were no treatment
      related adverse events. In patients treated with 2 GAD-alum doses, stimulated C
      peptide area under the curve had decreased significantly less (9  m: p  <  0.037;
      15 m: p  <  0.032; 21 m: p  <  0.003 and 30  m: p <  0.004), and a larger
      proportion of these patients were also able to achieve a peak stimulated C
      peptide > 0.2  nmol/L (p  <  0.05), as compared with placebo. CONCLUSION:
      Treatment with two doses of GAD-alum in children and adolescents with recent
      onset type 1 diabetes shows no adverse events and preserves residual insulin
      secretion.

PMID- 24302605
TI  - The utility of the lipid-laden macrophage index for the evaluation of aspiration
      in children.

PMID- 24302604
TI  - Blending gelators to tune gel structure and probe anion-induced disassembly.
AB  - Blending different low molecular weight gelators (LMWGs) provides a convenient
      route to tune the properties of a gel and incorporate functionalities such as
      fluorescence. Blending a series of gelators having a common bis-urea motif, and
      functionalised with different amino acid-derived end-groups and differing length
      alkylene spacers is reported. Fluorescent gelators incorporating 1- and 2-pyrenyl
      moieties provide a probe of the mixed systems alongside structural and
      morphological data from powder diffraction and electron microscopy.
      Characterisation of the individual gelators reveals that although the expected
      alpha-urea tape motif is preserved, there is considerable variation in the
      gelation properties, molecular packing, fibre morphology and rheological
      behaviour. Mixing of the gelators revealed examples in which: 1) the gels formed
      separate, orthogonal networks maintaining their own packing and morphology, 2)
      the gels blended together into a single network, either adopting the packing and
      morphology of one gelator, or 3) a new structure not seen for either of the
      gelators individually was created. The strong binding of the urea functionalities
      to anions was exploited as a means of breaking down the gel structure, and the
      use of fluorescent gel blends provides new insights into anion-mediated gel
      dissolution.

PMID- 24302608
TI  - The effects of colestilan versus placebo and sevelamer in patients with CKD 5D
      and hyperphosphataemia: a 1-year prospective randomized study.
AB  - BACKGROUND: This study compared the effects of short-term titrated colestilan (a
      novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated
      the safety and efficacy of colestilan over 1 year compared with sevelamer, in
      patients with chronic kidney disease (CKD) 5D. METHODS: This prospective
      multicentre study comprised a 4-week phosphate binder washout period, a 16-week
      short-term, flexible-dose, treatment period (including a 4-week placebo
      controlled withdrawal period) and a 40-week extension treatment phase. RESULTS:
      At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum
      phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo
      (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan
      than with placebo (P < 0.001). Both colestilan and sevelamer produced significant
      reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1
      year, and the proportion of patients achieving target levels of <=1.78 mmol/L
      (5.5 mg/dL) or <=1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and
      73.3%, respectively, for colestilan, and 66.9 and 77.4%, respectively, for
      sevelamer). Serum calcium level remained stable in the colestilan group but
      tended to increase slightly in the sevelamer group (end-of-study increase of
      0.035 mmol/L over baseline). Both binders produced similar reductions from
      baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a
      target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in
      both groups (50.7 and 85.3% for colestilan and 54.0 and 80.6% for sevelamer).
      Colestilan was generally well tolerated. CONCLUSIONS: Colestilan is effective and
      safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords
      similar long-term phosphorus and cholesterol reductions/responder rates to
      sevelamer.

PMID- 24302609
TI  - All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like
      syndrome': a RARe study.
AB  - BACKGROUND: Specific therapies that target vascular endothelial growth factor
      (VEGF) and its receptors have improved the survival of patients with metastatic
      cancers, but can induce side effects. Renal side effects (proteinuria,
      hypertension and renal failure) are underestimated. METHODS: The French RARe
      (Reins sous traitement Anti-VEGF Registre) study collects data on patients with
      cancer who had a renal biopsy because of major renal side effects during
      treatment with anti-VEGF drugs. RESULTS: We collected 22 renal biopsies performed
      16.2+/-10.6 months after the beginning of treatment; of which 21 had
      hypertension, mean proteinuria was 2.97+/-2.00 g/day and mean serum creatinine,
      134+/-117 umol/L. Thrombotic microangiopathy (TMA) was observed in 21 biopsy
      specimens, sometimes associated with acute tubular necrosis (ATN; n=4). TMA
      histological lesions were more important than the biological signs of TMA could
      suggest. Patients with ATN of >20% had higher serum creatinine levels than those
      with only TMA (231 versus 95 umol/L). Nephrin, podocin and synaptopodin were
      variably down-regulated in all renal biopsies. VEGF was down-regulated in all
      glomeruli. CONCLUSION: This study underlines the importance of regular clinical
      and biological cardiovascular and renal checking during all anti-VEGF therapies
      for cancer for early detection of renal dysfunction. Collaboration between
      oncologists and nephrologists is essential. In such cases, renal biopsy might
      help in appreciating the severity of the renal lesions and after
      multidisciplinary discussion whether or not it is safe to continue the treatment.

PMID- 24302610
TI  - 'Finding a balance' in involving patients in goal setting early after stroke: a
      physiotherapy perspective.
AB  - BACKGROUND AND PURPOSE: Collaborative goal setting (between patient and
      professional) confers benefits within stroke and neurological rehabilitation, and
      is recommended in clinical guidelines. However, evidence suggests that patient
      participation in rehabilitation goal setting is not maximized, particularly
      within the hospital setting. The purpose of this study was to investigate
      physiotherapists' perceptions about their experiences of collaborative goal
      setting with patients in the sub-acute stages after stroke, in the hospital
      setting. METHODS: This qualitative study employed constructivist grounded theory
      methodology. Nine physiotherapists, of varying experience, were selected using
      purposive then theoretical sampling from three National Health Service hospital
      stroke units in England. Semi-structured interviews were conducted, audio
      recorded and transcribed. Transcripts were coded and analysed using the constant
      comparative method of grounded theory to find common themes. RESULTS: Three
      themes emerged from the data: 1) 'coming to terms with stroke' - the individual
      patient journey; 2) the evolution of goal setting skill - the individual
      physiotherapist journey; and 3) 'finding a balance' - managing expectations and
      negotiating interactions. A provisional grounded theory was constructed, which
      highlighted that, from the physiotherapists' perspective, collaboration with
      patients within goal setting early after stroke involved finding a balance
      between numerous different drivers, which have the potential to compete. Patient
      directed and therapist-directed goal setting approaches could be viewed as
      opposite ends of a continuum, along which patient-centred goal setting is
      possible. DISCUSSION: Physiotherapists perceived that collaborating with patients
      in goal setting was important but challenging. Goal setting interactions with
      other professionals, patients and families were perceived as complex, difficult
      and requiring significant effort. The importance of individuality and temporality
      were recognized suggesting that the goal setting approach needs to be adapted to
      the context and the individuals involved.

PMID- 24302612
TI  - Automated cell block system for atypical glandular cells of cervical cytology: is
      it feasible?

PMID- 24302611
TI  - The ZZ domain of dystrophin in DMD: making sense of missense mutations.
AB  - Duchenne muscular dystrophy (DMD) is associated with the loss of dystrophin,
      which plays an important role in myofiber integrity via interactions with beta
      dystroglycan and other members of the transmembrane dystrophin-associated protein
      complex. The ZZ domain, a cysteine-rich zinc-finger domain near the dystrophin C
      terminus, is implicated in forming a stable interaction between dystrophin and
      beta-dystroglycan, but the mechanism of pathogenesis of ZZ missense mutations has
      remained unclear because not all such mutations have been shown to alter beta
      dystroglycan binding in previous experimental systems. We engineered three ZZ
      mutations (p.Cys3313Phe, p.Asp3335His, and p.Cys3340Tyr) into a short construct
      similar to the Dp71 dystrophin isoform for in vitro and in vivo studies and
      delineated their effect on protein expression, folding properties, and binding
      partners. Our results demonstrate two distinct pathogenic mechanisms for ZZ
      missense mutations. The cysteine mutations result in diminished or absent
      subsarcolemmal expression because of protein instability, likely due to
      misfolding. In contrast, the aspartic acid mutation disrupts binding with beta
      dystroglycan despite an almost normal expression at the membrane, confirming a
      role for the ZZ domain in beta-dystroglycan binding but surprisingly
      demonstrating that such binding is not required for subsarcolemmal localization
      of dystrophin, even in the absence of actin binding domains. 

PMID- 24302614
TI  - CHIP/Stub1 functions as a tumor suppressor and represses NF-kappaB-mediated
      signaling in colorectal cancer.
AB  - The carboxyl terminus of Hsc70-interacting protein (CHIP, also named Stub1), a U
      box containing E3 ubiquitin ligase, is involved in degradation of certain
      oncogenic proteins. Recent studies indicated that CHIP suppresses tumor
      progression in human cancers by targeting Src-3, hypoxia inducible factor 1alpha,
      NF-kappaB, ErbB2 and c-Myc. Here, we report that CHIP was downregulated,
      predominantly, in the late stages of human colorectal cancer (CRC), and that the
      CHIP promoter was hypermethylated in CRC specimens. Overexpression of CHIP in HCT
      116 cells resulted in impaired tumor growth in nude mice and decreased abilities
      of tumor cell migration and invasion. Conversely, depletion of CHIP in HCT-116
      cells promoted tumor growth and increased tumor cell migration and invasion. CHIP
      was further found to negatively regulate NF-kappaB signaling in HCT-116 cells by
      promoting ubiquitination and degradation of p65, a subunit of the NF-kappaB
      complex. The suppressive effect of CHIP led to decreased expression of NF-kappaB
      targeted oncogenes including Cyclin D1, c-Myc, MMP-2, VEGF and IL-8. We proposed
      that CHIP inhibits the malignancy of CRC cells, possibly through targeting NF
      kappaB signaling. This study provides functional evidence for CHIP as a potential
      tumor suppressor in CRC, and CHIP expression may be a marker for stages of CRC. 

PMID- 24302613
TI  - Emerging roles of the microbiome in cancer.
AB  - Gene-environment interactions underlie cancer susceptibility and progression.
      Yet, we still have limited knowledge of which environmental factors are important
      and how they function during tumorigenesis. In this respect, the microbial
      communities that inhabit our gastrointestinal tract and other body sites have
      been unappreciated until recently. However, our microbiota are environmental
      factors that we are exposed to continuously, and human microbiome studies have
      revealed significant differences in the relative abundance of certain microbes in
      cancer cases compared with controls. To characterize the function of microbiota
      in carcinogenesis, mouse models of cancer have been treated with antibiotics.
      They have also been maintained in a germfree state or have been colonized with
      specific bacteria in specialized (gnotobiotic) facilities. These studies
      demonstrate that microbiota can increase or decrease cancer susceptibility and
      progression by diverse mechanisms such as by modulating inflammation, influencing
      the genomic stability of host cells and producing metabolites that function as
      histone deacetylase inhibitors to epigenetically regulate host gene expression.
      One might consider microbiota as tractable environmental factors because they are
      highly quantifiable and relatively stable within an individual compared with our
      exposures to external agents. At the same time, however, diet can modulate the
      composition of microbial communities within our gut, and this supports the idea
      that probiotics and prebiotics can be effective chemoprevention strategies. The
      trajectory of where the current work is headed suggests that microbiota will
      continue to provide insight into the basic mechanisms of carcinogenesis and that
      microbiota will also become targets for therapeutic intervention. 

PMID- 24302616
TI  - 2,2,2-Trifluoroacetophenone as an organocatalyst for the oxidation of tertiary
      amines and azines to N-oxides.
AB  - A cheap, mild and environmentally friendly oxidation of tertiary amines and
      azines to the corresponding N-oxides is reported by using polyfluoroalkyl ketones
      as efficient organocatalysts. 2,2,2-Trifluoroacetophenone was identified as the
      optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This
      oxidation is chemoselective and proceeds in high-to-quantitative yields utilizing
      10 mol % of the catalyst and H2 O2 as the oxidant. 

PMID- 24302615
TI  - Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling
      and inhibits tumor growth in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most lethal malignancy worldwide with
      no curative therapies. To discover potentially novel therapeutic targets for HCC,
      we previously studied the gene expression profiles of HCC patients and identified
      that significant upregulation of N-Myc downstream regulated gene 1 (NDRG1) is
      associated with more aggressive phenotypes and poorer overall survival of HCC
      patients. In this study, we further used a loss-of-function approach (RNA
      interference) to understand the role of NDRG1 in hepatocarcinogenesis. We found
      that suppression of NDRG1 significantly impaired HCC cell growth through inducing
      extensive cellular senescence of HCC cells both in vitro and in vivo, accompanied
      by cell cycle arrest at the G1 phase. The observed antitumor effects of NDRG1
      suppression were correlated with activation of major senescence-associated
      signaling pathways, such as upregulation of tumor suppressors p53, p21 and p16,
      and decreased phosphorylated Rb. To obtain further insights into the clinical
      significance of NDRG1-modulated senescence in HCC patients, immunohistochemistry
      staining of 92 cases of HCC patients was done. We found that high NDRG1
      expression (n = 66) is associated with low p21 (n = 82; P < 0.001) and low p16 (n
      = 86; P < 0.001) levels. In conclusion, this study demonstrated that NDRG1 is a
      potential therapeutic target for HCC because its suppression triggers senescence
      of HCC cells through activating glycogen synthase kinase-3beta-p53 pathway,
      thereby inhibiting tumor progression. 

PMID- 24302617
TI  - Determination of cysteine, homocysteine, cystine, and homocystine in biological
      fluids by HPLC using fluorosurfactant-capped gold nanoparticles as postcolumn
      colorimetric reagents.
AB  - We have demonstrated for the first time the suitability of fluorosurfactant
      capped spherical gold nanoparticles as HPLC postcolumn colorimetric reagents for
      the direct assay of cysteine, homocysteine, cystine, and homocystine. The success
      of this work was based on the use of an on-line tris(2-carboxyethyl)phosphine
      reduction column for cystine and homocystine. Several parameters affecting the
      separation efficiency and the postcolumn colorimetric detection were thoroughly
      investigated. Under the optimized conditions, cysteine, homocysteine, cystine,
      and homocystine in human urine and plasma samples were determined. Detection
      limits for cysteine, homocysteine, cystine, and homocystine ranged from 0.16-0.49
      MUM. The accuracy in terms of recoveries ranged between 94.0-102.1%. This
      proposed method was rapid, inexpensive, and simple. 

PMID- 24302620
TI  - Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site
      recognition.
AB  - Mutations in SNRP200 gene cause autosomal-dominant retinal disorder retinitis
      pigmentosa (RP). The protein product of SNRNP200 is BRR2, a DExD/H box RNA
      helicase crucial for pre-mRNA splicing. In this study, we prepared p.S1087L and
      p.R1090L mutations of human BRR2 using bacterial artificial chromosome
      recombineering and stably expressed them in human cell culture. Mutations in BRR2
      did not compromise snRNP assembly and both mutants were incorporated into the
      spliceosome just as the wild-type (wt) protein. Surprisingly, cells expressing RP
      mutants exhibited increased splicing efficiency of the LDHA gene. Next, we found
      that depletion of endogenous BRR2 enhanced usage of a beta-globin cryptic splice
      site while splicing at the correct splice site was inhibited. Proper splicing of
      optimal and cryptic splice sites was restored in cells expressing BRR2-wt but not
      in cells expressing RP mutants. Taken together, our data suggest that BRR2 is an
      important factor in 5'-splice-site recognition and that the RP-linked mutations
      c.3260C>T (p.S1087L) and c.3269G>T (p.R1090L) affect this BRR2 function. 

PMID- 24302621
TI  - p16 INK4a overexpression and p16/Ki-67 dual labeling versus conventional urinary
      cytology in the evaluation of urothelial carcinoma.
AB  - BACKGROUND: Taking into consideration the known overexpression of p16(INK4a) in
      histologically demonstrated high-grade urothelial malignancies, the objective of
      the current study was to examine the value of p16(INK4a) overexpression and of
      p16/Ki-67 dual labeling versus urinary cytology in the detection of urothelial
      lesions. METHODS: Immunolabeling was performed on demounted and destained
      Papanicolaou slides after liquid-based ThinPrep processing. Actual diagnoses were
      ascertained by cystoscopy controls and histopathology. Negative cases, papillary
      urothelial neoplasia of low malignant potential/low-grade tumor, and high-grade
      lesions were considered separately. RESULTS: A total of 216 urine samples were
      collected from new patients with symptoms who were referred for cystoscopy (92
      cases) or patients who were being followed after conservative treatment for
      lesions involving the bladder (117 cases) or the upper urinary tract (7 cases).
      p16(INK4a) positivity was assessed in 171 of the 216 cases (79.2%) and in 93 of
      99 high-grade cases with positive cytology (93.9%). Coexpression of p16/Ki-67 in
      the same cells was observed in 119 of 216 cases (55.1%) and was noted in 18 of 51
      cases of negative or papillary urothelial neoplasia of low malignant
      potential/low-grade tumor (35.3%) and in 80 of 101 high-grade tumors (79.2%) (P <
      .0001). Thirteen of 14 high-grade intraurothelial lesions (92.8%) were dual
      labeled. When high-grade tumors, disease progression (increased grade, muscle
      infiltration, and extension into the upper urinary tract), and cancer-related
      death were grouped together as an endpoint, dual labeling demonstrated a
      sensitivity that was slightly higher than that of urinary cytology (82.5% vs
      80.8%; P = .8), with 94.9% overall specificity. CONCLUSIONS: When applied to the
      search for high-grade and aggressive disease, p16/Ki-67 dual labeling and urinary
      cytology appear to demonstrate comparable performance.

PMID- 24302622
TI  - Highly sensitive determination of polybrominated diphenyl ethers in surface water
      by GC coupled to high-resolution MS according to the EU Water Directive
      2008/105/EC.
AB  - The analysis of brominated flame retardants, such as polybrominated diphenyl
      ethers (PBDEs), has received increased interest because of their toxicity and
      ubiquity. According to European Union Directive 2008/105/EC, the development of
      highly sensitive and selective methods capable of determining PBDEs at low
      concentration levels (<0.5 ng/L) is necessary. In this work, an SPE method was
      developed for the analysis of the six PBDEs (BDE-28, BDE-47, BDE-99, BDE-100, BDE
      153, BDE-154) specified by the aforementioned directive in surface waters. The
      analyses were performed by GC coupled to magnetic sector high-resolution MS. The
      conditions were also optimized to detect the target compounds in water samples at
      concentrations below the environmental quality standards established by European
      legislation. The validated method provided adequate linearity (determination
      coefficient, R(2) >= 0.9960), recovery (101-120%, except for BDE-47 at 5 ng/L,
      127%), and precision values (RSD < 20%) at two fortification levels (0.2 and 5
      ng/L). The method showed LODs and LOQs ranging from 0.02 to 0.05 and from 0.05 to
      0.1 ng/L, respectively. The method was applied in surface water samples, allowing
      the determination of these compounds at the limits established by current
      legislation. 

PMID- 24302623
TI  - Hydroxymethylated phyllobilins: a puzzling new feature of the dioxobilin branch
      of chlorophyll breakdown.
AB  - Colorless nonfluorescent chlorophyll (Chl) catabolites (NCCs) are formyloxobilin
      type phyllobilins, which are considered the typical products of Chl breakdown in
      senescent leaves. However, in degreened leaves of some plants, dioxobilin-type
      Chl catabolites (DCCs) predominate, which lack the formyl group of the NCCs, and
      which arise from Chl catabolites by oxidative removal of the formyl group by a
      P450 enzyme. Here a structural investigation of the DCCs in the methylesterase16
      mutant of Arabidopsis thaliana is reported. Eight new DCCs were identified and
      characterized structurally. Strikingly, three of these DCCs carry
      stereospecifically added hydroxymethyl groups, and represent bilin-type linear
      tetrapyrroles with an unprecedented modification. Indeed, DCCs show a remarkable
      structural parallel, otherwise, to the bilins from heme breakdown. 

PMID- 24302624
TI  - A modified ELISA accurately measures secretion of high molecular weight
      hyaluronan (HA) by Graves' disease orbital cells.
AB  - Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space
      is a major component of Graves' ophthalmopathy, and regulation of HA production
      by orbital cells is a major research area. In most previous studies, HA was
      measured by ELISAs that used HA-binding proteins for detection and rooster comb
      HA as standards. We show that the binding efficiency of HA-binding protein in the
      ELISA is a function of HA polymer size. Using gel electrophoresis, we show that
      HA secreted from orbital cells is primarily comprised of polymers more than 500
      000. We modified a commercially available ELISA by using 1 million molecular
      weight HA as standard to accurately measure HA of this size. We demonstrated that
      IL-1beta-stimulated HA secretion is at least 2-fold greater than previously
      reported, and activation of the TSH receptor by an activating antibody M22 from a
      patient with Graves' disease led to more than 3-fold increase in HA production in
      both fibroblasts/preadipocytes and adipocytes. These effects were not
      consistently detected with the commercial ELISA using rooster comb HA as standard
      and suggest that fibroblasts/preadipocytes may play a more prominent role in HA
      remodeling in Graves' ophthalmopathy than previously appreciated. 

PMID- 24302625
TI  - An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter
      mutation provides a mouse model for endogenous glucocorticoid excess.
AB  - Cushing's syndrome, which is characterized by excessive circulating
      glucocorticoid concentrations, may be due to ACTH-dependent or -independent
      causes that include anterior pituitary and adrenal cortical tumors, respectively.
      ACTH secretion is stimulated by CRH, and we report a mouse model for Cushing's
      syndrome due to an N-ethyl-N-nitrosourea (ENU) induced Crh mutation at -120 bp of
      the promoter region, which significantly increased luciferase reporter activity
      and was thus a gain-of-function mutation. Crh(-120/+) mice, when compared with
      wild-type littermates, had obesity, muscle wasting, thin skin, hair loss, and
      elevated plasma and urinary concentrations of corticosterone. In addition, Crh(
      120/+) mice had hyperglycemia, hyperfructosaminemia, hyperinsulinemia,
      hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia but normal
      adiponectin. Crh(-120/+) mice also had low bone mineral density, hypercalcemia,
      hypercalciuria, and decreased concentrations of plasma PTH and osteocalcin. Bone
      histomorphometry revealed Crh(-120/+) mice to have significant reductions in
      mineralizing surface area, mineral apposition, bone formation rates, osteoblast
      number, and the percentage of corticoendosteal bone covered by osteoblasts, which
      was accompanied by an increase in adipocytes in the bone marrow. Thus, a mouse
      model for Cushing's syndrome has been established, and this will help in further
      elucidating the pathophysiological effects of glucocorticoid excess and in
      evaluating treatments for corticosteroid-induced osteoporosis. 

PMID- 24302626
TI  - Functional collaboration of insulin-like growth factor-1 receptor (IGF-1R), but
      not insulin receptor (IR), with acute GH signaling in mouse calvarial cells.
AB  - GH signals through the GH receptor (GHR), a cytokine receptor linked to Janus
      kinase 2 (JAK2). GH activates signal transducer and activator of transcription 5
      (STAT5), causing expression of genes including IGF-I. IGF-I binds IGF-I receptor
      (IGF-IR), a heterotetrameric (alpha2-beta2) tyrosine kinase growth factor
      receptor similar to insulin receptor (IR). In addition to this GH -> GHR -> IGF-I
      -> IGF-IR pathway, GH induces a complex including GHR, JAK2, and IGF-IR and
      deletion of floxed IGF-1R in primary murine calvarial cells with Cre-recombinase
      expressing adenovirus (Ad-Cre) desensitizes cells to GH for STAT5 activation and
      IGF-I mRNA accumulation. Diminished GH-induced STAT5 phosphorylation in Ad-Cre
      treated cells is rescued by adenoviruses encoding either IGF-IR or IGF-IR lacking
      the beta-chain intracellular domain. Reasoning that IGF-IR's extracellular
      portion (alpha or extracellular beta) mediates functional interaction with GH
      signaling, we pursued reconstitution studies. Although structurally related to
      IGF-IR, IR expressed adenovirally did not rescue GH-induced STAT5 phosphorylation
      in Ad-Cre-treated cells. We thus created chimeras, swapping homologous IR
      extracellular regions into IGF-IR. IR and IGF-IR possess N-terminal L1, cysteine
      rich (CR), and L2 alpha-chain domains. We created Ad-IGF-IR/IR-L1 and Ad-IGF
      IR/IR-L1-CR-L2, in which L1 alone or L1, CR, and L2 of IR replace corresponding
      IGF-IR regions, respectively. Ad-IGF-IR/IR-L1, but not Ad-IGF-IR/IR-L1-CR-L2,
      rescued GH-induced STAT5 phosphorylation in Ad-Cre-treated cells. Additionally,
      medium containing a soluble IGF-IR (including only L1-CR-L2) dampened GH-induced
      STAT5 phosphorylation in calvarial cells and two other GH-responsive cell lines.
      Thus, an extracellular determinant(s), likely in CR-L2, specifically allows IGF
      IR to collaborate with GHR and JAK2 for robust GH-induced acute STAT5
      phosphorylation. 

PMID- 24302628
TI  - Eugen Steinach: the first neuroendocrinologist.
AB  - In 1936, Eugen Steinach and colleagues published a work that brought steroid
      biochemistry to the study of sexual behavior and, using synthetic androgens and
      estrogens, foreshadowed by an astonishing 4 decades the discovery of the central
      role of estrogen in the sexual behavior of male rats. We offer an English
      translation of that paper, accompanied by historical commentary that presents
      Steinach as a pioneer in reproductive neuroendocrinology. His work 1) established
      the interstitial cells as the main source of mammalian gonadal hormones; 2)
      launched the hypothesis that steroid hormones act on the brain to induce sexual
      behavior and that chronic gonadal transplants produce sexual reversals in
      physiology and behavior; 3) demonstrated the influence of sensory stimulation on
      testicular function; and finally 4) spearheaded the development of synthetic
      commercial hormones for clinical use in humans. Although its applications were
      controversial, Steinach's research was confirmed by many, and his concepts were
      applied to fields such as oncology and vascular disease. His contemporaries
      lauded his research, as indicated by his 7 Nobel Prize nominations. But
      Steinach's basic research was rarely acknowledged as the field flourished after
      1950. The translation and our commentary attempt to reverse that neglect among
      behavioral neuroendocrinologists and clarify his central role as a founder of the
      neuroendocrinology of sexual behavior and reproduction. 

PMID- 24302627
TI  - Activation of angiotensin type 2 receptors partially ameliorates streptozotocin
      induced diabetes in male rats by islet protection.
AB  - We have previously demonstrated that rat islets express a high density of
      angiotensin type 2 receptors and that activation of this receptor evokes
      insulinotropic effect. In this study, we evaluated the protective effects of
      Compound 21 (C21), a nonpeptide angiotensin type 2 receptor agonist, on islets in
      streptozotocin (STZ)-induced diabetes. Rats were assigned to five groups: normal,
      STZ, and STZ plus C21 (0.24, 0.48, and 0.96 mg/kg.d). C21 was continually infused
      by a sc implanted osmotic minipump for 14 days, and STZ was bolus injected on day
      7. Body weight, water intake, urine excretion, and blood glucose were monitored
      daily. On the last day, the rats received an oral glucose tolerance test, and the
      pancreata were saved to examine islet morphology and biochemical parameters of
      oxidative stress and apoptosis. We found that, compared with control STZ rats,
      C21-treated STZ rats displayed less water intake and urine excretion, lower blood
      glucose, higher serum insulin concentration, and improved glucose tolerance.
      These rats had more islets, larger islet mass, and up-regulated insulin protein
      and proinsulin 2 mRNA expressions in the pancreas. Their islets displayed lower
      superoxide, decreased gp91 expression, and increased superoxide dismutase 1
      expression as well as less apoptosis and down-regulated caspase-3 expression. In
      the epididymal adipose tissue of these rats, we found a decreased adipocyte size
      and up-regulated adipocyte protein 2 expression. The protective effects of C21 on
      beta-cells against the toxic effects of STZ were also confirmed in cultured INS
      1E cells. These data suggest that C21 ameliorates STZ-induced diabetes by
      protecting pancreatic islets via antioxidative and antiapoptotic effects. 

PMID- 24302629
TI  - A novel truncated form of eNOS associates with altered vascular function.
AB  - AIMS: Nitric oxide (NO) plays a key role in vascular homeostasis and is produced
      by endothelial NO synthase (eNOS), encoded by NOS3 gene. We previously reported
      the genetic association between NOS3 rs753482-A>C polymorphism on intron 19 and
      coronary artery disease (CAD). In the attempt of conferring functional
      implication to the rs753482-A>C polymorphism, we investigated its influence on
      transcript maturation. METHODS AND RESULTS: A transcript variant skipping exons
      20-21 is prevalent in carriers of the rs753482-C allele and is translated in a
      novel truncated form of eNOS. The truncated eNOS displays increased basal NO
      production, is insensitive to calcium stimulation, and, upon heterodimerization
      with the full-length eNOS protein, exerts a dominant-negative effect on NO
      production. CAD patients and healthy subjects' carriers of the rs753482-C
      genotype are characterized by increased NO basal levels in peripheral blood and
      platelets, and negatively respond to oral glucose load by failing to increase NO
      synthesis following insulin wave. Furthermore, forearm vasodilation after
      reactive hyperaemia is dramatically impaired in rs753482-C carriers. CONCLUSIONS:
      We demonstrated that subjects carrying the rs753482-C genotype express a novel
      stable truncated form of eNOS with altered enzymatic activity that influences NO
      production and endothelial function. These findings open to new intriguing
      perspectives to several diseases involving vascular response to NO.

PMID- 24302630
TI  - Damage-associated molecular pattern activated Toll-like receptor 4 signalling
      modulates blood pressure in L-NAME-induced hypertension.
AB  - AIMS: Recent publications have shed new light on the role of the adaptive and
      innate immune system in the pathogenesis of hypertension. However, there are
      limited data whether receptors of the innate immune system may influence blood
      pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key
      component of the innate immune system, which is activated by exogenous and
      endogenous ligands. Hypertension is associated with end-organ damage and thus
      might lead to the release of damage-associated molecular patterns (DAMPs), which
      are endogenous activators of TLR4 receptors. The present study aimed to elucidate
      whether TLR4 signalling is able to modulate vascular contractility in an
      experimental model of hypertension thus contributing to blood pressure
      regulation. METHODS AND RESULTS: NG-nitro-l-arginine methyl ester (l-NAME)
      induced hypertension was blunted in TLR4(-/-) when compared with wild-type mice.
      Treatment with l-NAME was associated with a release of DAMPs, leading to reactive
      oxygen species production of smooth muscle cells in a TLR4-dependent manner. As
      oxidative stress leads to an impaired function of the NO-sGC-cyclic GMP (cGMP)
      pathway, we were able to demonstrate that TLR4(-/-) was protected from sGC
      inactivation. Consequently, arterial contractility was reduced in TLR4(-/-).
      CONCLUSIONS: Cell damage-associated TLR4 signalling might act as a direct
      mediator of vascular contractility providing a molecular link between
      inflammation and hypertension.

PMID- 24302631
TI  - RGC-5 cells.

PMID- 24302633
TI  - Multicomponent reactions in polymer synthesis.
AB  - More participants, yet efficient reactions: Multicomponent reactions (MCRs) have
      found application in polymer chemistry both in the synthesis of multifunctional
      monomers and in post-polymerization modification. Examples include the Passerini
      three-component reaction, the Ugi four-component reaction, and the copper
      catalyzed MCR. 

PMID- 24302632
TI  - Germline mutations of inhibins in early-onset ovarian epithelial tumors.
AB  - To identify novel genetic bases of early-onset epithelial ovarian tumors, we used
      the trio exome sequencing strategy in a patient without familial history of
      cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of
      age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the
      INHBA gene encoding the betaA-subunit of inhibins/activins, which play a key role
      in ovarian development. In vitro, this mutation alters the ratio of secreted
      activins and inhibins. In a second patient with early-onset serous borderline
      papillary cystadenoma, we identified an unreported germline mutation
      (c.179G>T/p.Arg60Leu) of the INHA gene encoding the alpha-subunit, the partner of
      the betaA-subunit. This mutation also alters the secreted activin/inhibin ratio,
      by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases,
      we detected an additional unreported germline mutation of the INHBA gene
      (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations
      contribute to the genetic determinism of epithelial ovarian tumors. 

PMID- 24302634
TI  - Everyday discrimination is associated with nicotine dependence among African
      American, Latino, and White smokers.
AB  - INTRODUCTION: Discrimination is a commonly perceived stressor among African
      Americans and Latinos, and previous research has linked stress with substance
      dependence. Although studies have shown a link between discrimination and
      smoking, little is known about the relationship between discrimination and
      nicotine dependence. METHODS: A total of 2,376 African American (33.4%; n = 794),
      Latino (33.1%; n = 786), and White (33.5%; n = 796) smokers completed an online
      survey. Everyday discrimination experiences were described in total and by
      race/ethnicity. Covariate-adjusted linear regression analyses were conducted to
      evaluate the associations between everyday discrimination and indicators of
      nicotine dependence. RESULTS: Most participants (79.1%), regardless of
      race/ethnicity, reported experiencing everyday discrimination. However, total
      scores on the discrimination measure were higher among Latinos and African
      Americans than among Whites (p < .001). Race/ethnicity/national origin was the
      most commonly perceived reason for everyday discrimination among African
      Americans and Latinos, whereas physical appearance was the most commonly
      perceived reason among Whites. Regression analyses indicated that everyday
      discrimination was positively associated with indicators of nicotine dependence,
      including the Heaviness of Smoking Index (HSI; p < .001) and the Brief Wisconsin
      Inventory of Smoking Dependence Motives (WISDM) scales (all ps < .001). There was
      a significant interaction between race/ethnicity and discrimination, such that
      discrimination was associated with the HSI only among Latinos. Similarly,
      discrimination was most strongly associated with the WISDM scales among Latinos.
      CONCLUSIONS: Analyses indicated that discrimination is a common stressor
      associated with nicotine dependence. Findings suggest that greater nicotine
      dependence is a potential pathway through which discrimination may influence
      health.

PMID- 24302635
TI  - Comparison of tobacco-containing and tobacco-free waterpipe products: effects on
      human alveolar cells.
AB  - INTRODUCTION: In recent years, a class of products marketed as "tobacco-free"
      alternatives for the "health conscious user" has become widely available for
      waterpipe (hookah, narghile, or shisha) smoking. Their adoption may be in part
      driven by regulations banning tobacco smoking in public places and by an
      increasing awareness of the hazards of waterpipe tobacco smoking. Although these
      products are presented in advertising as a "healthier" choice, very little is
      known about their health effects. METHODS: In this study, we compared the effects
      of smoke generated with tobacco-free and conventional tobacco-derived products on
      human alveolar cells. Smoke was generated with a smoking machine that precisely
      mimicked the puffing behavior of 15 experienced waterpipe smokers when they used
      conventional waterpipe tobacco products of their choice and flavor-matched
      tobacco-free products. Human alveolar epithelial cells (A549) were treated with
      particulate matter sampled from the smoke, and the effects on cell cycle,
      proliferation, and doubling time were measured during the subsequent 72hr.
      RESULTS: We found that smoke from both types of waterpipe products markedly
      reduced cell proliferation, caused cell cycle arrest at G0/G1, and increased cell
      doubling time. There were no significant differences across product in any
      measure. CONCLUSION: Tobacco-free and tobacco-based waterpipe products exert
      substantial and similar deleterious effects on human lung cells. This study adds
      to the nascent evidence base indicating that except for exposure to nicotine and
      its derivatives, use of tobacco-free waterpipe products does not present a
      reduced health risk relative to the use of conventional tobacco-based products.

PMID- 24302636
TI  - Summary of the SRNT treatment network Webinar: getting SMART about developing
      individualized sequences of health interventions.

PMID- 24302637
TI  - Smoke-free homes, strength of smoke-free law, and children in the home.
AB  - INTRODUCTION: Secondhand smoke (SHS) is a leading cause of childhood illness and
      premature death, especially in rural areas. The study examined the relationship
      of having a smoke-free home, strength of smoke-free law (SFL) in the county of
      residence, having one or more minor children in the home, rural/urban location,
      and demographics. METHODS: An Internet-based panel survey was administered to
      Kentucky residents from 2007 to 2012. Sample size ranged from 400 to 513 per
      year; N = 2,653 total. Most were female, aged 35-54, had at least some college
      education, and lived in a smoke-free home. Almost half lived in a county with a
      comprehensive SFL; 14% lived in a county with a moderate or weak law. RESULTS:
      Multivariate logistic regression revealed that the significant predictors of a
      smoke-free home included having education beyond high school, being a nonsmoker,
      living in an urban county, and having a year of participation in the survey.
      Controlling for smoking status and other personal characteristics, those who
      responded to the survey in the last 2 years of administration were more likely to
      have a smoke-free home compared to the reference year of 2007. Respondents living
      in urban counties were nearly 2 times more likely to report a smoke-free home
      than rural dwellers. CONCLUSIONS: Smoke-free homes in urban areas, where SFLs may
      be the norm, may be more typical than in rural communities. Public awareness
      campaigns and education about the benefits of smoke-free homes is needed,
      especially in rural areas, targeting smokers, those with less education, and
      those with children living in the home.

PMID- 24302638
TI  - Brief exposure to secondhand smoke reversibly impairs endothelial vasodilatory
      function.
AB  - INTRODUCTION: We sought to determine the effects of brief exposures to low
      concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated
      dilation (FMD, a nitric oxide-dependent measure of vascular endothelial
      function), in a controlled animal model never before exposed to smoke. In humans,
      SHS exposure for 30 min impairs FMD. It is important to gain a better
      understanding of the acute effects of exposure to SHS at low concentrations and
      for brief periods of time. METHODS: We measured changes in FMD in rats exposed to
      a range of real-world levels of SHS for durations of 30 min, 10 min, 1 min, and 4
      breaths (roughly 15 s). RESULTS: We observed a dose-response relationship between
      SHS particle concentration over 30 min and post-exposure impairment of FMD, which
      was linear through the range typically encountered in smoky restaurants and then
      saturated at higher concentrations. One min of exposure to SHS at moderate
      concentrations was sufficient to impair FMD. CONCLUSIONS: Brief SHS exposure at
      real-world levels reversibly impairs FMD. Even 1 min of SHS exposure can cause
      reduction of endothelial function.

PMID- 24302639
TI  - Stability of human papillomavirus (HPV) in cervical ThinPrep specimens previously
      lysed with glacial acetic acid: effect on cobas 4800 HPV test performance.
AB  - BACKGROUND: The authors previously demonstrated that lysing samples with glacial
      acetic acid (GAA) before human papillomavirus (HPV) testing does not adversely
      affect HPV detection with the cobas 4800 HPV Test. However, the long-term impact
      of GAA on HPV DNA was not explored in that study, and inherent cell loss with the
      lysing protocol used also was observed. The current study considered the long
      term effects of GAA treatment of cervical ThinPrep samples on HPV detection with
      the cobas 4800 HPV Test. They also modified the manufacturer's lysing procedure
      for ThinPrep specimens to help prevent cell loss. METHODS: Seventy-eight ThinPrep
      samples, including previously lysed, archived specimens, were split; then, 1 part
      was treated with GAA according to the manufacturer's protocol or using a modified
      protocol, and the other part was left untreated. All samples were tested for HPV
      using the cobas 4800 HPV Test. The HPV-positive/HPV-negative status of tested
      samples was used to determine the level of agreement between treated and
      untreated fractions. Performance of the modified lysing procedure was assessed
      relative to the manufacturer's protocol. RESULTS: Positive HPV status produced
      97% agreement between the GAA-treated/untreated fractions. Concordance between
      the GAA-treated/untreated fractions did not differ between the 2 lysing methods;
      however, the average percentage increases in beta-globin and HPV cycle threshold
      values after lysing were less discernible for the modified lysing method.
      CONCLUSIONS: GAA treatment of cervical ThinPrep specimens does not have long-term
      adverse effects on HPV detection with the cobas 4800 HPV Test. The manufacturer's
      GAA lysing procedure for ThinPrep specimens can be reliably modified for
      specimens that may subsequently undergo HPV testing.

PMID- 24302640
TI  - Enantiospecific, regioselective cross-coupling reactions of secondary allylic
      boronic esters.

PMID- 24302641
TI  - Systematic comparison of a new generation of columns packed with sub-2 MUm
      superficially porous particles.
AB  - The aim of this study was to evaluate the possibilities/limitations of recent RP
      LC columns packed with 1.6 MUm superficially porous particles (Waters Cortecs)
      and to compare its potential to other existing sub-2 MUm core-shell packings. The
      kinetic performance of Kinetex 1.3 MUm, Kinetex 1.7 MUm and Cortecs 1.6 MUm
      stationary phases was assessed. It was found that the Kinetex 1.3 MUm phase
      outperforms its counterparts for ultra-fast separations. Conversely, the Cortecs
      1.6 MUm packing seemed to be the best stationary phase for assays with longer
      analysis time in isocratic and gradient modes, considering small molecules and
      peptides as test probes. This exceptional behaviour was attributed to its
      favourable permeability and somewhat higher mechanical stability (DeltaPmax of
      1200 bar). The loading capacity of these three columns was also investigated with
      basic and neutral drugs analysed under acidic conditions. It appears that the
      loading capacities of Cortecs 1.6 MUm and Kinetex 1.7 MUm were very close, while
      it was reduced by 2-7-fold on the Kinetex 1.3 MUm packing. However, this
      observation is dependent on the nature of the compound and certainly also on
      mobile phase conditions. 

PMID- 24302642
TI  - Porous TiO2 nanowire microsphere constructed by spray drying and its
      electrochemical lithium storage properties.
AB  - Porous TiO2 nanowire microspheres with greatly decreasing agglomeration were
      successfully prepared by spray drying of hydrothermal reaction suspension,
      followed by calcination at 350 degrees C. The as-obtained nanowire microspheres
      with TiO2-B structure reach an initial discharge capacity 210 mAh g(-1) with an
      irreversible capacity 25 mAh g(-1) at a current density of 20 mA g(-1). For the
      450 degrees C-calcined one with anatase TiO2 crystal structure, the initial
      discharge capacity is 245 mAh g(-1) but with a much higher irreversible capacity
      of 80 mAh g(-1). The hierarchical porous structure in the 350 degrees C-calcined
      TiO2 nanowire microspheres collapsed at 450 degrees C, annihilating the main
      benefit of nanostructuring.

PMID- 24302643
TI  - Highly luminescent thin films of the dense framework infinity(3)[EuIm2] with
      switchable transparency formed by scanning femtosecond-pulse laser deposition.
AB  - Highly luminescent switchable thin films of the dense framework
      infinity(3)[EuIm2] were deposited by a scanning laser ablation technique using a
      femtosecond laser. The films can be controlled in terms of film thickness and
      amount of material deposited such that the material properties of the bulk
      material are retained on the nanometer scale. Polycrystalline films are formed
      that can be switched between transparent at visible light and nontransparent at
      UV light due to the intrinsic luminescence of the hybrid material, expanding the
      concept of smart films. The new femtosecond pulsed laser deposition method also
      provides a novel approach for coatings with framework compounds and coordination
      polymers.

PMID- 24302645
TI  - On the mechanism of the organocatalytic asymmetric epoxidation of alpha,beta
      unsaturated aldehydes.
AB  - Mechanistic studies on the organocatalytic epoxidation of alpha,beta-unsaturated
      aldehydes explore the autoinductive behavior of the reaction and establish that
      the hydrate/peroxyhydrate of the product is acting as a phase-transfer catalyst.
      Based on these studies, an improved methodology that provides high selectivities
      and decreased catalyst loading, through the addition of chloral hydrate, is
      developed. 

PMID- 24302644
TI  - Effects of stretch and shortening on gene expression in intact myocardium.
AB  - Multiple cues have been suggested as the mechanical stimulus for the heart's
      hypertrophic response. Our work has previously suggested that the amount of
      cyclic shortening in cardiomyocytes controls myocyte shape and the amount of
      stretch controls myocyte size. To identify gene expression changes that occur in
      response to these mechanical perturbations, we used microarray analysis of
      papillary muscles cultured for 12 h at physiological or reduced levels of cyclic
      shortening and physiological or reduced mean stretch. Overall, genes related to
      extracellular matrix (ECM) were surprisingly prominent in our analysis.
      Connective tissue growth factor was among a small group of genes regulated by the
      amount of cyclic shortening regardless of the level of mean stretch, and many
      more ECM genes were regulated by shortening with reduced amounts of stretch. When
      we compared our results to gene expression data from an in vivo model of pressure
      overload (PO), which also decreases myocyte shortening, we found the genes that
      were commonly regulated in PO and our decreased shortening groups were most
      significantly enriched for ontology terms related to the ECM, followed by genes
      associated with mechanosensing and the cytoskeleton. The list of genes regulated
      in PO and our decreased shortening groups also includes genes known to change
      early in hypertrophy, such as myosin heavy chain 7, brain natriuretic peptide,
      and myosin binding protein C. We conclude that in intact myocardium, the amount
      of cyclic shortening may be an important regulator not only of myocyte genes
      classically associated with hypertrophy but also of ECM genes. 

PMID- 24302646
TI  - Three-phase hollow-fiber liquid-phase microextraction combined with HPLC-UV for
      the determination of isothiazolinone biocides in adhesives used for food
      packaging materials.
AB  - The present study deals with the development of a liquid microextraction
      procedure for enhancing the sensitivity of the determination of 2-methyl-4
      isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one in adhesives. The
      procedure involves a three-phase hollow-fiber liquid-phase microextraction using
      a semipermeable polypropylene membrane, which contained 1-octanol as the organic
      phase in the pores of the membrane. The donor and acceptor phases are aqueous
      acidic and alkaline media, respectively, and the final liquid phase (acceptor) is
      analyzed by HPLC coupled with diode array detection. The most appropriate
      conditions were extraction time 20 min, stirring speed 1400 rpm, extraction
      temperature 50 degrees C. The quantification limits of the method were 0.123 and
      0.490 MUg/g for 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4
      isothiazolin-3-one, respectively. Three different adhesive samples were
      successfully analyzed. The procedure was compared to direct analysis using ultra
      high pressure liquid chromatography coupled with TOF-MS, where the identification
      of the compounds and the quantification values were confirmed. 

PMID- 24302647
TI  - MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic
      carcinoma from pleomorphic adenoma in fine-needle aspiration biopsy specimens.
AB  - BACKGROUND: The distinction between adenoid cystic carcinoma (ACC) and
      pleomorphic adenoma (PA) on fine-needle aspiration biopsy (FNAB) can be
      challenging. Recently, a specific translocation t(6;9) involving the v-myb avian
      myeloblastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) genes
      was identified in ACCs, in which it contributes to MYB overexpression. The
      authors investigated the use of MYB immunocytochemistry in FNAB specimens as an
      ancillary test for the cytologic diagnosis of ACC. METHODS: The expression of MYB
      was assessed in alcohol-fixed cytologic smears of histologically confirmed ACCs
      (n = 20) and PAs (n = 20) using immunocytochemistry. The corresponding ACCs and
      PAs from formalin-fixed, paraffin embedded surgical resection specimens also were
      stained immunohistochemically for MYB. The nuclear expression of MYB was assessed
      semiquantitatively using a scoring system (from 0 to 6) that combined the
      proportion and the intensity of staining. A score >=4 was considered positive,
      and a score <=3 was considered negative. RESULTS: On FNAB material, 80% of ACCs
      (N = 16 of 20) were immunocytochemically positive for MYB. In contrast, all PAs
      (N = 20 of 20) were negative for MYB (P < .0001). The sensitivity of MYB on FNAB
      was 80%, and the specificity was 100% relative to PA. Results on corresponding
      histology were similar to the cytology results; however, there was often a zonal
      staining pattern with central areas of tumor (range, 20%-90%) that lacked
      immunoreactivity, thus suggesting that the immunoreactivity was maintained better
      in alcohol-fixed FNAB material. CONCLUSIONS: In contrast to PAs, a majority of
      ACCs are immunocytochemically positive for MYB. The test is more effective using
      alcohol-fixed FNAB material and is potentially useful for the cytologic
      distinction of ACC and PA.

PMID- 24302648
TI  - Interaction of proteins with aluminum(III)-chlorophosphonazo III by resonance
      Rayleigh scattering method.
AB  - In weak acid medium, aluminum(III) can react with chlorophosphonazo III
      [CPA(III), H(8)L] to form a 1:1 coordination anion [Al(OH)(H(4)L)](2-). At the
      same time, proteins such as bovine serum albumin (BSA), lysozyme (Lyso) and human
      serum albumin (HSA) existed as large cations with positive charges, which further
      combined with [Al(OH)(H(4)L)](2-) to form a 1:4 chelate. This resulted in
      significant enhancement of resonance Rayleigh scattering (RRS), second-order
      scattering (SOS) and frequency doubling scattering (FDS). In this study, we
      investigated the interaction between [Al(OH)(H(4)L)](2-) and proteins,
      optimization of the reaction conditions and the spectral characteristics of RRS,
      SOS and FDS. The maximum RRS wavelengths of different protein systems were
      located at 357-370 nm. The maximum SOS and FDS wavelengths were located at 546
      and 389 nm, respectively. The scattering intensities (DeltaI) of the three
      methods were proportional to the concentration of the proteins, within certain
      ranges, and the detection limits of the most sensitive RRS method were 2.6-9.3
      ng/mL. Moreover, the chelate reaction mechanism or the reasons for the
      enhancement of RRS were discussed through absorption spectra, fluorescence
      spectra and circular dichroism (CD) spectra.

PMID- 24302649
TI  - Enantioselective organocatalytic multicomponent synthesis of 2,6
      diazabicyclo[2.2.2]octanones.

PMID- 24302650
TI  - Double knockout mutants of Arabidopsis grown under normal conditions reveal that
      the plastidial phosphorylase isozyme participates in transitory starch
      metabolism.
AB  - In leaves of two starch-related single-knockout lines lacking either the
      cytosolic transglucosidase (also designated as disproportionating enzyme 2, DPE2)
      or the maltose transporter (MEX1), the activity of the plastidial phosphorylase
      isozyme (PHS1) is increased. In both mutants, metabolism of starch-derived
      maltose is impaired but inhibition is effective at different subcellular sites.
      Two constitutive double knockout mutants were generated (designated as dpe2
      1*phs1a and mex1*phs1b) both lacking functional PHS1. They reveal that in
      normally grown plants, the plastidial phosphorylase isozyme participates in
      transitory starch degradation and that the central carbon metabolism is closely
      integrated into the entire cell biology. All plants were grown either under
      continuous illumination or in a light-dark regime. Both double mutants were
      compromised in growth and, compared with the single knockout plants, possess less
      average leaf starch when grown in a light-dark regime. Starch and chlorophyll
      contents decline with leaf age. As revealed by transmission electron microscopy,
      mesophyll cells degrade chloroplasts, but degradation is not observed in plants
      grown under continuous illumination. The two double mutants possess similar but
      not identical phenotypes. When grown in a light-dark regime, mesophyll
      chloroplasts of dpe2-1*phs1a contain a single starch granule but under continuous
      illumination more granules per chloroplast are formed. The other double mutant
      synthesizes more granules under either growth condition. In continuous light,
      growth of both double mutants is similar to that of the parental single knockout
      lines. Metabolite profiles and oligoglucan patterns differ largely in the two
      double mutants.

PMID- 24302652
TI  - Redundancy in the periplasmic adaptor proteins AcrA and AcrE provides resilience
      and an ability to export substrates of multidrug efflux.
AB  - OBJECTIVES: The components of the AcrAB-TolC efflux pump function as a tripartite
      efflux system conferring resistance to multiple antibiotics and the individual
      components can also function in conjunction with other efflux pumps. This study
      aimed to establish whether redundancy exists between the homologous periplasmic
      adaptor proteins (PAPs) AcrA and AcrE and to measure the impact of this
      redundancy on antimicrobial resistance and the potential efficacy of inhibitor
      molecules. METHODS: The acrE gene was inactivated in Salmonella enterica serovar
      Typhimurium SL1344 and a DeltaacrA mutant by insertion of the aph gene. The
      mutants were complemented with plasmids carrying acrA or acrE. The antimicrobial
      susceptibility of the mutants to various antimicrobials was determined and the
      accumulation or efflux of various substrates was measured. RESULTS: Inactivation
      of acrE alone had no phenotypic effect. However, the effect of inactivation of
      PAPs was additive; the acrA acrE mutant was more susceptible to certain
      antimicrobials and accumulated more Hoechst dye than single acrA, acrE or acrB
      mutants. In addition, the double mutant invaded human intestinal epithelial cells
      poorly. The phenotypic defects of the acrA acrE mutant were ameliorated by
      expression of either acrA or acrE, but the proteins exhibited some substrate
      specificity. CONCLUSIONS: These data show for the first time the level of
      redundancy between the PAPs AcrA and AcrE, and highlight the PAPs as excellent
      targets for inhibitor molecules that could be used to potentiate the action of
      clinical antimicrobials. However, the redundancy that exists between AcrA and
      AcrE means potential inhibitors must act on both targets to be effective.

PMID- 24302651
TI  - A novel hybrid SCCmec-mecC region in Staphylococcus sciuri.
AB  - OBJECTIVES: Methicillin resistance in Staphylococcus spp. results from the
      expression of an alternative penicillin-binding protein 2a (encoded by mecA) with
      a low affinity for beta-lactam antibiotics. Recently, a novel variant of mecA
      known as mecC (formerly mecALGA251) was identified in Staphylococcus aureus
      isolates from both humans and animals. In this study, we identified two
      Staphylococcus sciuri subsp. carnaticus isolates from bovine infections that
      harbour three different mecA homologues: mecA, mecA1 and mecC. METHODS: We
      subjected the two isolates to whole-genome sequencing to further understand the
      genetic context of the mec-containing region. We also used PCR and RT-PCR to
      investigate the excision and expression of the SCCmec element and mec genes,
      respectively. RESULTS: Whole-genome sequencing revealed a novel hybrid SCCmec
      region at the orfX locus consisting of a class E mec complex (mecI-mecR1-mecC1
      blaZ) located immediately downstream of a staphylococcal cassette chromosome mec
      (SCCmec) type VII element. A second SCCmec attL site (attL2), which was
      imperfect, was present downstream of the mecC region. PCR analysis of stationary
      phase cultures showed that both the SCCmec type VII element and a hybrid SCCmec
      mecC element were capable of excision from the genome and forming a circular
      intermediate. Transcriptional analysis showed that mecC and mecA, but not mecA1,
      were both expressed in liquid culture supplemented with oxacillin. CONCLUSIONS:
      Overall, this study further highlights that a range of staphylococcal species
      harbour the mecC gene and furthers the view that coagulase-negative staphylococci
      associated with animals may act as reservoirs of antibiotic resistance genes for
      more pathogenic staphylococcal species.

PMID- 24302653
TI  - Rilpivirine, emtricitabine and tenofovir resistance in HIV-1-infected rilpivirine
      naive patients failing antiretroviral therapy.
AB  - OBJECTIVES: In the context of simplification strategies, it is essential to know
      the feasibility of a switch to a rilpivirine-based therapy. The aim of this study
      was to describe rilpivirine, tenofovir and emtricitabine resistance in HIV-1
      infected patients who experienced virological failure during their previous
      antiretroviral treatment. PATIENTS AND METHODS: The studied population included
      two groups of patients, all rilpivirine naive, tested for resistance by bulk
      sequencing from 2008 to 2011: the first group (n = 998) failing a nucleoside
      reverse transcriptase inhibitor (NRTI) plus boosted protease inhibitor (PI)-based
      regimen and the second group (n = 3733) failing an NRTI plus non-nucleoside
      reverse transcriptase inhibitor (NNRTI)-based regimen. RESULTS: In the first
      group, the frequency of rilpivirine mutations and resistance to rilpivirine
      (5.1%) was similar to that in antiretroviral-naive HIV-1-infected patients. Among
      the 1605 patients from the second group with at least one NNRTI mutation in their
      HIV, the prevalence of viruses 'resistant' or 'possibly resistant' to efavirenz,
      nevirapine and etravirine was 78%, 79% and 74%, respectively, while 59% were
      resistant to rilpivirine. Resistance to rilpivirine was significantly more
      frequent in non-B subtype versus B subtype viruses. Among pretreated patients
      with viruses with at least one NNRTI mutation (other than for rilpivirine), 22%
      of sequences were susceptible to the combination
      rilpivirine/emtricitabine/tenofovir disoproxil fumarate. CONCLUSIONS: In patients
      failing an NRTI plus NNRTI-based regimen, to know the feasibility of a switch to
      rilpivirine/emtricitabine/tenofovir disoproxil fumarate, reliable resistance
      information should be available at the time of use of concurrent NNRTI therapy.

PMID- 24302654
TI  - Direct aldol strategy in enantioselective total synthesis of thuggacin B.
AB  - An enantioselective total synthesis of thuggacin B, a natural product exhibiting
      antibiotic activity against Mycobacterium tuberculosis, is described. Asymmetric
      direct aldol reactions promoted by Cu and Zn catalysts play a pivotal role in
      constructing four stereogenic centers. The use of direct aldol reactions as the
      initial steps for the synthesis of two key fragments allowed the construction of
      the other stereogenic centers through chirality transfer.

PMID- 24302655
TI  - Comparison of fine-needle aspiration and fine-needle capillary sampling of
      thyroid nodules: a prospective study with emphasis on the influence of nodule
      size.
AB  - BACKGROUND: The objective of this study was to compare the sampling efficiency of
      ultrasound-guided fine-needle aspiration (FNA) and fine-needle capillary (FNC)
      sampling in thyroid nodules, in which the authors specifically analyzed the
      influence of nodule size. METHODS: This study included 280 thyroid nodules in 275
      consecutive patients. The nodules were divided into 4 size subgroups: <=5.0 mm,
      from 5.1 to 10.0 mm, from 10.1 to 20.0 mm, and >20.0 mm. Each nodule was sampled
      by both FNA and FNC. The final cytopathologic findings were reported. The smears
      were scored and then categorized as diagnostically inadequate, adequate, or
      superior on the basis of 4 parameters, which included background clot or blood,
      the number of obtained cells, preserved tissue architecture, and cellular
      degeneration. RESULTS: The kappa scores for agreement of the cytopathologic
      results between FNA and FNC sampling in the 4 size subgroups were 0.377, 0.455,
      0.751, and 0.352 for nodules that measured <=5.0 mm, from 5.1 to 10.0 mm, from
      10.1 to 20.0 mm, and >20.0 mm, respectively. The proportion of nondiagnostic of
      FNAs was significantly lower than the proportion of nondiagnostic FNC samples in
      nodules that measured >20.0 mm (P = .037). Scores for the 4 diagnostic parameters
      were significantly greater in FNAs than in FNC samples in nodules that measured
      from 5.1 to 10.0 mm and >20.0 mm (all P < .05); however, similar results were not
      observed in the nodules that measured <=5.0 mm or from 10.1 to 20.0 mm (all P >
      .05). Also, FNA yielded significantly more diagnostically superior specimens than
      FNC sampling in nodules that measured from 5.1 to 10.0 mm and >20.0 mm (P < .05
      for both). CONCLUSIONS: The current findings indicated that FNA may be more
      suitable than FNC for sampling nodules that measure from 5.1 to 10.0 mm and >20.0
      mm; whereas, for nodules that measure <=5.0 mm and from 10.1 to 20.0 mm, the 2
      techniques could yield specimens with similar quality.

PMID- 24302656
TI  - Detection and dynamics of different carbendazim-resistance conferring beta
      tubulin variants of Gibberella zeae collected from infected wheat heads and rice
      stubble in China.
AB  - BACKGROUND: Carbendazim has been used in the control of Fusarium head blight
      (FHB) for more than 30 years in China. Thus, carbendazim-resistant (Car(R) )
      populations of Gibberella zeae have developed in some areas. In this study, 9341
      G. zeae isolates were collected from the ten main wheat-producing regions of
      China in the period from 2008 to 2012, and sensitivity to carbendazim was
      detected. RESULTS: A high frequency of Car(R) isolates was observed in Zhejiang
      and Jiangsu provinces. Car(R) isolates were recovered from Anhui and Henan
      provinces in 2009 and 2012, respectively, but were not detected in the other six
      regions. Available (F167Y, E198Q and F200Y) and newly developed (E198L and E198K)
      allele-specific PCR assays were used to genotype field Car(R) isolates. The beta
      tubulin variants harbouring point mutation F167Y or E198Q accounted for >95% in
      Car(R) populations. Quantitative allele-specific real-time PCR assays were
      developed to determine the frequencies of five different beta-tubulin variants
      present in populations of perithecia sampled from rice stubble. CONCLUSION:
      Car(R) populations of G. zeae develop rapidly under the selection pressure of
      carbendazim. Real-time PCR assays detecting the resistance frequencies in
      populations of perithecia would provide useful information for FHB control and
      management of resistance.

PMID- 24302657
TI  - Simple SPE-GC method for anethole determination in human serum.
AB  - Recently, much attention has been given to congener analysis, which can be used
      to check the possibility of postoffence drinking claims in forensic toxicology.
      In this type of analysis, the information given by the defendant regarding the
      type, quantity, and time of consumption of a specific alcoholic beverage is used
      to calculate theoretically expected congener concentration in the blood and this
      is compared with the analytically determined concentrations in the blood sample.
      Many alcoholic drinks aromatized with essential oils of plants and fruits contain
      a specific congener, for example, anethole in aniseed drinks. The present study
      describes the GC procedure of anethole analysis in human plasma using SPE as the
      sample preparation method. The procedure involves the protein precipitation
      process, which generally degrades the protein-analyte complex, and SPE isolation
      of anethole from the examined materials. This analytical approach is proposed as
      a method of choice for the estimation of anethole concentration in human fluids
      after the consumption of alcoholic beverages and other foods containing the
      substance. The described method is characterized by a low LOD (8.33 ng/g) and a
      very high recovery (average recovery 98.37%) of the analyte. 

PMID- 24302658
TI  - Role of myosin Va in neuritogenesis of chick dorsal root ganglia nociceptive
      neurons.
AB  - Myosin-Va, widely distributed throughout the developing nervous system, is
      involved in the transport of vesicles and other intracellular components with its
      globular tail domain (GTD) implicated in cargo recognition/interaction.
      Inactivation of myosin-Va in dorsal root ganglia (DRG) neurons of chick embryos,
      in vitro, decreases the rate of filopodial extension. MYO5A mutant mice have
      severe neurological defects. We have found that the overexpression of GTD in DRG
      cultures reduces the number of neurons with long neurites (above fourfold cell
      body length) and increased the number of neurons with short or no neurites.
      However, if transfection occurred after the onset of neuritogenesis, this was not
      seen. In embryo, we characterized the expression pattern of myosin-Va during
      neuritogenesis of TrkA-positive cells at different stages of chick DRG
      development. Myosin-Va expression was detected starting from HH25. At this stage,
      it was present in cells both with and without neurites. The presence of myosin-Va
      in DRG neurites persisted throughout the last stage analysed (HH34). The data
      suggest that Myosin Va can participate in embryonic DRG neuritogenesis. 

PMID- 24302659
TI  - Guest-adaptable and water-stable peptide-based porous materials by imidazolate
      side chain control.
AB  - The peptide-based porous 3D framework, ZnCar, has been synthesized from Zn(2+)
      and the natural dipeptide carnosine (beta-alanyl-L-histidine). Unlike previous
      extended peptide networks, the imidazole side chain of the histidine residue is
      deprotonated to afford Zn-imidazolate chains, with bonding similar to the
      zeolitic imidazolate framework (ZIF) family of porous materials. ZnCar exhibits
      permanent microporosity with a surface area of 448 m(2)  g(-1) , and its pores
      are 1D channels with 5 A openings and a characteristic chiral shape. This
      compound is chemically stable in organic solvents and water. Single-crystal X-ray
      diffraction (XRD) showed that the ZnCar framework adapts to MeOH and H2 O guests
      because of the torsional flexibility of the main His-beta-Ala chain, while
      retaining the rigidity conferred by the Zn-imidazolate chains. The conformation
      adopted by carnosine is driven by the H bonds formed both to other dipeptides and
      to the guests, permitting the observed structural transformations. 

PMID- 24302660
TI  - An image case of necrotising fasciitis: a severe postoperative complication.

PMID- 24302661
TI  - Pneumatosis intestinalis associated with enteral tube feeding.
AB  - A 49-year-old man presented with a Hinchey II perforated diverticulitis and
      underwent laparoscopic peritoneal lavage. During the postoperative course the
      patient received enteral tube feeding which was followed by a bowel obstruction
      accompanied with pneumatosis intestinalis (PI). Explorative laparotomy showed an
      omental band adhesion without signs of ischaemia. After a short period of total
      parenteral nutrition PI resolved almost completely and enteral tube feeding could
      be continued once again. In the weeks that followed the patient developed
      atypical bowel symptoms and recurrent PI which resolved each time the drip
      feeding was discontinued. Despite the mild clinical course, a CT scan showed
      massive PI on day 21 after the laparotomy. After excluding life-threatening
      conditions conservative management was instituted and the patient recovered
      completely after discontinuing the drip feeding. We present one of the few cases
      of subclinical PI associated with enteral tube feeding that could be managed
      conservatively. 

PMID- 24302662
TI  - A sneeze: an unusual trigger for aortic dissection.
AB  - We describe a rare case of type B thoracic aortic dissection resulting from a
      forceful sneeze in a 57-year-old man. The presenting clinical features were not
      typical and consisted of pleuritic chest pain and breathlessness following a
      forceful sneeze. There was no haemodynamic compromise. The diagnosis was made
      incidentally when he underwent a CT pulmonary angiography as part of pulmonary
      embolism work-up. 

PMID- 24302663
TI  - Werner's syndrome: incidental finding during pregnancy.
AB  - Werner's syndrome (WS) is a rare autosomal recessive disorder, characterised by
      skin changes prematurely during adolescence. An unusual case of WS was found in a
      27-year-old pregnant woman who presented to the hospital with a history of
      uncontrolled hypertension at 32 weeks of gestation. All clinical features
      corresponding to WS (early aging of skin, hair loss, blurred vision and diabetes
      type 2) appeared to match with the prospective diagnosis, which was confirmed
      later with genetic testing. The pregnancy became complicated due to
      oligohydramnios and therefore a caesarean section was carried out in order to
      preserve the fetus. Despite all implemented efforts, the patient died
      intraoperative as a result of cardiac arrest and its complications. Successfully,
      the newborn survived and it was further investigated to exclude this condition. 

PMID- 24302664
TI  - Streptokinase therapy in the treatment of neonatal obstructive renal candidiasis.
AB  - A 6-week-old ex-25-week gestation male infant developed candidal sepsis with
      subsequent bilateral acute obstructive nephropathy that was not responsive to
      intravenous antifungal therapy. Bilateral percutaneous nephrotomies were
      performed and irrigation with fluconazole started. Owing to the persistence of
      the candidaemia and left renal obstruction, streptokinase was administered
      through the nephrostomy with eventual resolution of obstruction and improvement
      in his kidney function. This case report discusses the use of the streptokinase
      therapy as an adjunct therapy in the clearance of fungal bezoars. 

PMID- 24302665
TI  - NRF2 immunolocalization in human breast cancer patients as a prognostic factor.
AB  - Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important
      transcriptional activator involved in the cellular defense mechanisms against
      electrophilic and oxidative stress. Recent studies have demonstrated that the
      expression of NRF2 protein is upregulated in several human malignancies and is
      associated with worse prognosis in these patients. However, the pathological and
      clinical significance of NRF2 has remained largely unknown in breast cancer
      patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast
      carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the
      breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was
      significantly associated with histological grade, Ki-67 labeling index, p62
      immunoreactivity, and NAD(P)H: quinone oxidoreductase 1 (NQO1) immunoreactivity,
      and the results of multivariate analyses revealed that NRF2 status was an
      independent adverse prognostic factor for both recurrence and disease-free
      survival of the patients. Subsequent in vitro studies demonstrated that the
      expression of NRF2 significantly increased the proliferation activity of MCF7 and
      SK-BR-3 breast carcinoma cells. These results indicate that nuclear NRF2 protein
      plays important roles in the proliferation and/or progression of breast
      carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent
      prognostic factor in breast cancer patients.

PMID- 24302666
TI  - Sorafenib in the treatment of radioiodine-refractory differentiated thyroid
      cancer: a meta-analysis.
AB  - The advent of biologically targeted agents and increased understanding of thyroid
      carcinogenesis have generated much interest in the development of biologically
      targeted therapeutic agents for thyroid cancer. Among them, sorafenib is the most
      commonly studied drug. The current meta-analysis was carried out to estimate the
      efficacy and safety of sorafenib administered in radioiodine-refractory
      differentiated thyroid cancer patients. An electronic search was conducted using
      PubMed/MEDLINE and EMBASE. Statistical analyses were carried out using either
      random-effects or fixed-effects models according to heterogeneity. All the
      statistical analyses were carried out using the Stata version 12.0 software.
      Seven eligible studies were identified. The final results indicated that 22% of
      the patients (95% CI: 15-28) achieved a partial response. Hand-foot syndrome,
      diarrhea, fatigue, rash, weight loss, and hypertension were the most frequently
      observed adverse effects (AEs) associated with sorafenib use and the incidence of
      these AEs (all grades) was 80% (95% CI: 68-91), 68% (95% CI: 59-77), 67% (95% CI:
      57-78), 66% (95% CI: 50-82), 52%(95% CI: 33-72), and 31% (95% CI: 21-42)
      respectively. Sixty-two percent (95% CI: 36-89) patients required dose reductions
      due to toxicity of sorafenib. As far as PR and AEs are concerned, the results of
      this meta-analysis indicate that sorafenib has a modest effect in patients with
      radioiodine-refractory differentiated thyroid cancer and the high incidence of
      AEs associated with this agent may affect the quality of patients' lives. Though
      the use of sorafenib in the treatment of radioiodine-refractory differentiated
      thyroid cancer is considered promising by most physicians working in this field,
      more effective agents with less toxicity and cost are still needed. 

PMID- 24302667
TI  - The role of the inflammatory microenvironment in thyroid carcinogenesis.
AB  - Immune responses against thyroid carcinomas have long been demonstrated and
      associations between inflammatory microenvironment and thyroid carcinomas
      repeatedly reported. This scenario has prompted scientists throughout the world
      to unveil how the inflammatory microenvironment is established in thyroid tumors
      and what is its influence on the outcome of patients with thyroid carcinoma. Many
      studies have reported the role of evasion from the immune system in tumor
      progression and reinforced the weakness of the innate immune response toward
      thyroid cancer spread in advanced stages. Translational studies have provided
      evidence that an increased density of tumor-associated macrophages in poorly
      differentiated thyroid carcinoma (DTC) is associated with an aggressive phenotype
      at diagnosis and decreased cancer-related survival, whereas well-DTC
      microenvironment enriched with macrophages is correlated with improved disease
      free survival. It is possible that these different results are related to
      different microenvironments. Several studies have provided evidence that patients
      whose tumors are not infiltrated by lymphocytes present a high recurrence rate,
      suggesting that the presence of lymphocytes in the tumor microenvironment may
      favor the prognosis of patients with thyroid carcinoma. However, the effect of
      lymphocytes and other immune cells on patient outcome seems to result from
      complex interactions between the tumor and immune system, and the molecular
      pattern of cytokines and chemokines helps to explain the involvement of the
      immune system in thyroid tumor progression. The inflammatory microenvironment may
      help to characterize aggressive tumors and to identify patients who would benefit
      from a more invasive approach, probably sparing the vast majority of patients
      with an indolent disease from unnecessary procedures. 

PMID- 24302668
TI  - Game changer: how informatics moved from a supporting role to a central position
      in healthcare.

PMID- 24302671
TI  - Cross-linked starch-based polymer as an SPE material for the determination of
      nitrophenols at trace levels in environmental water.
AB  - SPE using a cross-linked starch-based polymer (CSMDI) as an adsorbent for the
      determination of four nitrophenols at trace levels from aqueous solution was
      investigated. The CSMDI was synthesized from native starch using 4,4'
      methylenebisphenyldiisocyanate as a cross-linking agent in dry DMF. Parameters
      affecting the extraction efficiency including the pH of the water sample, type of
      eluent and its volume, flow rate, sample volume, and methanol content were
      investigated and optimized. The optimized results exhibited excellent linear
      relationships (R(2) > 0.995) for all the nitrophenols over the range of 2.0-200
      ng/mL, with the RSD values in the range of 2.9-5.7% (n = 5). The LODs ranged from
      0.08-0.34 ng/mL (S/N = 3) for the four nitrophenols tested under optimum
      conditions. The developed method has been successfully applied for the analysis
      of several real environmental water samples including tap, river, and reservoir
      water. These results indicated that the CSMDI had a tremendous potential for the
      enrichment and determination of nitrophenols at trace levels in environmental
      water samples. 

PMID- 24302672
TI  - Conversion of a disulfide bond into a thioacetal group during echinomycin
      biosynthesis.
AB  - Echinomycin is a nonribosomal depsipeptide natural product with a range of
      interesting bioactivities that make it an important target for drug discovery and
      development. It contains a thioacetal bridge, a unique chemical motif derived
      from the disulfide bond of its precursor antibiotic triostin A by the action of
      an S-adenosyl-L-methionine-dependent methyltransferase, Ecm18. The crystal
      structure of Ecm18 in complex with its reaction products S-adenosyl-L
      homocysteine and echinomycin was determined at 1.50 A resolution. Phasing was
      achieved using a new molecular replacement package called AMPLE, which
      automatically derives search models from structure predictions based on ab initio
      protein modelling. Structural analysis indicates that a combination of proximity
      effects, medium effects, and catalysis by strain drives the unique transformation
      of the disulfide bond into the thioacetal linkage.

PMID- 24302669
TI  - Electronic health records-driven phenotyping: challenges, recent advances, and
      perspectives.

PMID- 24302673
TI  - Global perspective of herbicide-resistant weeds.
AB  - Two hundred and twenty weed species have evolved resistance to one or more
      herbicides, and there are now 404 unique cases (species * site of action) of
      herbicide-resistant weeds globally. ALS inhibitor-resistant weeds account for
      about a third of all cases (133/404) and are particularly troublesome in rice and
      cereals. Although 71 weed species have been identified with triazine resistance,
      their importance has dwindled with the shift towards Roundup Ready(r) crops in
      the USA and the reduction of triazine usage in Europe. Forty-three grasses have
      evolved resistance to ACCase inhibitors, with the most serious cases being Avena
      spp., Lolium spp., Phalaris spp., Setaria spp. and Alopecurus myosuroides,
      infesting more than 25 million hectares of cereal production globally. Of the 24
      weed species with glyphosate resistance, 16 have been found in Roundup Ready(r)
      cropping systems. Although Conyza canadensis is the most widespread glyphosate
      resistant weed, Amaranthus palmeri and Amaranthus tuberculartus are the two most
      economically important glyphosate-resistant weeds because of the area they infest
      and the fact that these species have evolved resistance to numerous other
      herbicide sites of action, leaving growers with few herbicidal options for their
      control. The agricultural chemical industry has not brought any new herbicides
      with novel sites of action to market in over 30 years, making growers reliant on
      using existing herbicides in new ways. In addition, tougher registration and
      environmental regulations on herbicides have resulted in a loss of some
      herbicides, particularly in Europe. The lack of novel herbicide chemistries being
      brought to market combined with the rapid increase in multiple resistance in
      weeds threatens crop production worldwide.

PMID- 24302674
TI  - DNA topoisomerase II-dependent control of the cell cycle progression in root
      meristems of Allium cepa.
AB  - The catalytic ability of DNA topoisomerases (Topo) to generate short-term DNA
      breaks allow these enzymes to play crucial functions in managing DNA topology
      during S-phase replication, transcription, and chromatin-remodelling processes
      required to achieve commitment for the onset and transition through mitosis. Our
      experiments on root meristem cells of onion (Allium cepa) were designed to gain
      insight into the contribution of Topo II to plant-specific progression throughout
      interphase and mitosis. Irrespective of the position of the cell in interphase,
      the immunofluorescence of Topo II revealed similar nuclear labelling pattern with
      well defined signals dispersed in the nucleoplasm and the cortical zone of the
      nucleolus. Only weak labelling was detected in metaphase and anaphase
      chromosomes. Experiments with two potent anti-Topo II agents, doxorubicin (DOX,
      an anthracycline) and a bisdioxopiperazine derivative, ICRF-193, suggest that the
      inhibition-mediated increase in Topo II immunofluorescence may represent a
      compensatory mechanism, by which an up-regulated expression of the enzyme tends
      to counteract the drug-induced loss of indispensable catalytic and relaxation
      functions. gamma-H2AX immunolabelling seems to indicate that both DOX- and ICRF
      193-induced alterations in cell cycle progression reflect primarily the activity
      of the G2/M DNA damage checkpoint. Our findings provide evidence for the plant
      specific cell cycle control mechanism induced by Topo II inhibitors under DNA
      stress conditions. 

PMID- 24302676
TI  - Selective hydrosilation of CO2 to a bis(silylacetal) using an anilido bipyridyl
      ligated organoscandium catalyst.
AB  - A rigid anilido bipyridyl ligand has been designed for use in an organoscandium
      based carbon dioxide hydrosilation catalyst. Ligand attachment by alkane
      elimination results in metalation of an aryl C-H bond in a 3,5-di-tert
      butylphenyl group installed on the pyridyl unit, thus rendering the ligand
      tetradentate. Insertion of CO2 into the newly formed Sc-C bond leads to a
      kappa(1) carboxylate which, when treated with the borane B(C6F5)3, becomes
      hemilabile. In addition to activating the catalyst, the k(1) carboxylate
      effectively sequesters free B(C6F5)3 and the ensemble is able to effectively
      hydrosilate CO2, in the presence of excess Et3SiH, almost exclusively to
      R3SiOCH2OSiR3. A maximum turnover number of about 3400 (conversion of silane) is
      observed. Mechanistic experiments suggest that the sequestration of free B(C6F5)3
      by the hemilabile carboxylate contributes to the selectivity observed and
      prevents over reduction to methane.

PMID- 24302675
TI  - The bitter taste receptor T2R38 is an independent risk factor for chronic
      rhinosinusitis requiring sinus surgery.
AB  - BACKGROUND: The bitter taste receptor T2R38 was recently described to play a role
      in upper airway innate mucosal defense. When activated by bacterial quorum
      sensing molecules, T2R38 stimulates the ciliated epithelial cells to produce
      nitric oxide (NO), resulting in bactericidal activity and an increase in
      mucociliary clearance (MCC). Polymorphisms within the T2R38 gene (TAS2R38) confer
      variability in activation of the receptor yielding dramatic differences in upper
      airway defensive responses (NO production and accelerated MCC) to microbial
      stimulation based on genotype. Our objective was to determine whether the
      nonprotective TAS2R38 polymorphisms, which render the receptor inactive,
      correlate with medically recalcitrant chronic rhinosinusitis (CRS) necessitating
      surgical intervention in the context of known risk factors, and thus identify
      whether the TAS2R38 genotype is an independent risk factor for patients
      undergoing functional endoscopic sinus surgery (FESS). METHODS: CRS patients
      undergoing primary FESS were prospectively genotyped for TAS2R38. Chi-square
      analysis was performed on the genotype distribution with respect to other risk
      factors, including allergies, asthma, nasal polyposis, aspirin sensitivity,
      diabetes, and smoking exposure. RESULTS: Seventy primary FESS patients were
      genotyped demonstrating a statistically significant skewing from the expected
      distribution of the general population (p < 0.0383). CRS patients with a
      particular polymorphism seemed less likely to have allergies, asthma, nasal
      polyposis, aspirin sensitivity, and diabetes, but this did not demonstrate
      statistical significance. CONCLUSION: Our investigation suggests that TAS2R38
      genotype is an independent risk factor for patients failing medical therapy,
      necessitating surgical intervention.

PMID- 24302678
TI  - Reliability-targeted HPLC-UV method validation--a protocol enrichment
      perspective.
AB  - Method validation is important in analytical chemistry to obtain the reliability
      of an analytical method. Guidelines provided by the regulatory bodies can be used
      as a general framework to assess the validity of a method. Since these guidelines
      do not focus on the reliability of analytical results exclusively, this study was
      aimed to combine a few recently evolved strategies that may render analytical
      method validation more reliable and trustworthy. In this research, the analytical
      error function was determined by appropriate polynomial regression statistics
      that determine the range of analyte concentration that may lead to more accurate
      measurements by producing the least possible total error in the assay and can be
      regarded as a reliable weighting method. The reliability of the analytical
      results over a particular concentration range has been proposed by a Bayesian
      probability study. In order to ensure the applicability of this approach, it was
      applied for the validation of an HPLC-UV assay method dedicated to the
      quantification of cefepime and tazobactam in human plasma. A comparison between
      the newer approach and the usual method validation revealed that the application
      of analytical error function and Bayesian analysis at the end of the validation
      process can produce significant improvements in the analytical results. 

PMID- 24302677
TI  - A population-based evaluation of cervical screening in the United States: 2008
      2011.
AB  - BACKGROUND: Cervical screening consumes substantial resources, but little is
      known about utilization in the United States or compliance with guideline
      recommendations. METHODS: To describe population screening coverage, utilization,
      and outcomes and examine time trends from 2008 to 2011, cervical cytology reports
      from women residing in New Mexico (981,063 tests from 511,381 women) were
      evaluated. RESULTS: From 2008 to 2011 cervical screening utilization decreased at
      all ages, but especially in younger women, with a two-third reduction at ages 15
      to 20 years. Ninety-four percent of women ages 25 to 29 years were screened
      within 48 months but coverage decreased at older ages to 69% at 45 to 49 years
      and 55% at 60 to 64 years. Intervals between screening tests were significantly
      longer in 2011 compared with 2008 [HR = 1.23; 95% confidence intervals (CI), 1.22
      1.24], although the commonest rescreening interval was 13 months. In 2011, 91.9%
      of screening tests for women ages 21 to 65 years were negative, 6.6% showed minor
      abnormalities, and 1.0% high-grade abnormalities. High-grade abnormality rates
      were relatively constant over time, but minor abnormalities and atypical cells
      cannot rule out high-grade (ASC-H) were increasing. CONCLUSIONS: This population
      based evaluation of cervical screening shows high coverage under the age of 40
      years, but lower levels in older women. Screening under age 21 years is becoming
      less common and screening intervals are lengthening, reflecting updates in
      national screening guidelines. IMPACT: Assessment of cervical screening intervals
      and population outcomes is essential for accurately estimating the impact and
      effectiveness of changing recommendations and vaccination against human papilloma
      virus infections.

PMID- 24302679
TI  - Dark chocolate consumption improves leukocyte adhesion factors and vascular
      function in overweight men.
AB  - Flavanol-enriched chocolate consumption increases endothelium-dependent
      vasodilation. Most research so far has focused on flow-mediated dilation (FMD)
      only; the effects on other factors relevant to endothelial health, such as
      inflammation and leukocyte adhesion, have hardly been addressed. We investigated
      whether consumption of regular dark chocolate also affects other markers of
      endothelial health, and whether chocolate enrichment with flavanols has
      additional benefits. In a randomized double-blind crossover study, the effects of
      acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal
      flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count,
      plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45
      70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate
      were also collected. Findings showed that a 4 wk chocolate intake increased FMD
      by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell
      count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion
      marker expression (P<0.05 for time effect), with no difference between HFC and
      NFC consumption. Flavanol enrichment did affect taste and negatively affected
      motivation to consume chocolate. This study provides new insights on how
      chocolate affects endothelial health by demonstrating that chocolate consumption,
      besides improving vascular function, also lowers the adherence capacity of
      leukocytes in the circulation.

PMID- 24302680
TI  - Degradation of three benzonitrile herbicides by Aminobacter MSH1 versus soil
      microbial communities: pathways and kinetics.
AB  - BACKGROUND: The herbicide dichlobenil was banned in the European Union after its
      metabolite 2,6-dichlorobenzamide (BAM) was encountered in groundwater. Owing to
      structural similarities, bromoxynil and ioxynil might be converted to persistent
      metabolites in a similar manner. To examine this, we used an indigenous soil
      bacterium Aminobacter sp. MSH1 which is capable of mineralizing dichlobenil via
      BAM and 2,6-dichlorobenzoic acid (2,6-DCBA). RESULTS: Strain MSH1 converted
      bromoxynil and ioxynil to the corresponding aromatic metabolites, 3,5-dibromo-4
      hydroxybenzoic acid (BrAC) and 3,5-diiodo-4-hydroxybenzoic acid (IAC) following
      Michaelis-Menten kinetics (adjusted R(2) between 0.907 and 0.999). However, in
      contrast to 2,6-DCBA, degradation of these metabolites was not detected in the
      pure-culture studies, suggesting that they might pose an environmental risk if
      similar partial degradation occurred in soil. By contrast, experiments with
      natural soils indicated 20-30% mineralization of ioxynil and bromoxynil within
      the first week. CONCLUSION: The degradation pathway of the three benzonitriles is
      initially driven by similar enzymes, after which more specific enzymes are
      responsible for further degradation. Ioxynil and bromoxynil mineralization in
      soil is not dependent on previous benzonitrile exposure. The accumulation of dead
      end metabolites, as seen for dichlobenil, is not a major problem.

PMID- 24302682
TI  - Inverse relationship between gestational weight gain and glucose uptake in human
      placenta from female foetuses.
AB  - BACKGROUND: Maternal obesity and gestational weight gain (GWG) have a significant
      impact on the in utero environment, and thus on foetal development and the health
      of the offspring later in life. OBJECTIVE: The aim of this study was to determine
      the effect of maternal pre-existing obesity and maternal GWG on glucose uptake
      from placentas from male and female offspring. METHODS: Total glucose uptake was
      measured in placental explants using radio-labelled glucose. RESULTS: In the
      female placentas (n = 36), GWG and glucose uptake were significantly negatively
      correlated (r = -0.7, P < 0.0001; n = 36), and customized birthweight centile
      correlated with placental glucose uptake (r = 0.36, P = 0.03) but not GWG. In the
      male placentas (n = 45), GWG and glucose uptake were not related, and customized
      birthweight centile correlated with GWG (r = 0.34, P = 0.02; n = 45), but not
      placental glucose uptake. CONCLUSIONS: The female placenta can adapt glucose
      uptake in the face of excessive GWG. The male placenta showed no evidence of
      changing glucose uptake in response to maternal GWG.

PMID- 24302683
TI  - Hot-spot residues in the cytochrome P450cam-putidaredoxin binding interface.
AB  - Cytochrome P450cam (P450cam) is a heme-containing monooxygenase that catalyzes
      the hydroxylation of D-camphor to produce 5-exo-hydroxycamphor. The catalytic
      cycle of P450cam requires two electrons, both of which are donated by
      putidaredoxin (Pdx), a ferredoxin containing a [2 Fe-2 S] cluster. Atomic
      resolution structures of the Pdx-P450cam complex have recently been solved by X
      ray crystallography and paramagnetic NMR spectroscopy. The binding interface
      showed the potential electron transfer pathways and interactions between Pdx
      Asp38 and P450cam Arg112, as well as hydrophobic contacts between the Pdx Trp106
      and P450cam residues. Several polar residues not previously recognized as
      relevant for binding were found in the interface. In this study, site-directed
      mutagenesis, kinetic measurements, and NMR studies were employed to probe the
      energetic importance and role of the polar residues in the Pdx-P450cam
      interaction. A double mutant cycle (DMC) analysis of kinetic data shows that
      favorable interactions exist between Pdx Tyr33 and P450cam Asp125, as well as
      between Pdx Ser42 and P450cam His352. The results show that alanine substitutions
      of these residues and several others do not influence the rates of electron
      transfer. It is concluded that these polar interactions contribute to partner
      recognition rather than to electronic coupling of the redox centers.

PMID- 24302684
TI  - Cybertaxonomy to accomplish big things in aphid systematics.
AB  - Biodiversity sciences have progressed at such a pace that the taxonomic community
      has been unable to grow concomitantly to keep up with the influx of biological
      data. This "taxonomic impediment" has led some to suggest that taxonomy is no
      longer pertinent and to the development of methodologies that circumvent the
      taxonomic process. This article does not seek to argue for the importance of
      taxonomy but rather is a call to the aphid taxonomy community to rise to the
      challenge by dramatically increasing the volume and comprehensiveness of its
      output without sacrificing quality. Recent informatics technology allows us to
      mobilize the 2 most important aphid taxonomy resources: experts and specimens,
      both distributed globally. "Cyberspecimens," museum specimens digitally rendered
      at a resolution sufficient for remote identification, and open "cybertaxonomic"
      tools will allow the international aphid taxonomic community to carry out large,
      ambitious, projects. The global aphid cybertaxonomy proposed here will serve not
      only the ends of research aphidologists, but also provide a model for other
      taxonomic communities to adapt and adopt as we confront both the taxonomic
      impediment and the taxonomic naysayers. 

PMID- 24302681
TI  - The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting
      state amygdala connectivity.
AB  - The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral
      components of the stress response and exert positive modulatory effects on
      emotion in both human and animal studies. Although these antidepressant and
      anxiolytic effects have been well established, to date, little research has
      examined their neural correlates, and no research has been conducted into the
      effects of neurosteroids on large-scale networks at rest. To investigate the
      neurosteroid impact on intrinsic connectivity networks, participants were
      administered 400 mg of pregnenolone (N = 16), 400 mg of DHEA (N = 14), or placebo
      (N = 15) and underwent 3T fMRI. Resting-state brain connectivity was measured
      using amygdala as a seed region. When compared with placebo, pregnenolone
      administration reduced connectivity between amygdala and dorsal medial prefrontal
      cortex, between amygdala and precuneus, and between amygdala and hippocampus.
      DHEA reduced connectivity between amygdala and periamygdala and between amygdala
      and insula. Reductions in amygdala to precuneus connectivity were associated with
      less self-reported negative affect. These results demonstrate that neurosteroids
      modulate amygdala functional connectivity during resting state and may be a
      target for pharmacological intervention. Additionally, allopregnanolone and DHEA
      may shift the balance between salience network and default network, a finding
      that could provide insight into the neurocircuitry of anxiety psychopathology.

PMID- 24302685
TI  - Older adults' perceptions of physical activity: a qualitative study.
AB  - The purpose of this study was to explore older adults' perceptions of
      participation in physical activity (PA) as it impacts productive ageing and
      informs occupational therapy (OT) practice. In this phenomenological study, 15
      community-dwelling older adults were recruited using purposive and snowball
      sampling at community locations. Data collection methods included two interviews
      and an observation. The primary finding was that older adults continue individual
      patterns of meaningful PA across their lifespan when they have support to adapt
      to age-associated limitations, with a gradual decline in intensity during older
      years. Although this study's qualitative methodology limits broad
      generalizability, the findings provide applicability when situated in the context
      of community-living older adults interested in health maintenance through PA
      participation. OT practitioners have an important role with community-dwelling
      older adults to impact productive ageing by designing and promoting meaningful PA
      with adaptations that address unique, age-associated concerns. There is a need
      for further experimental research taking an occupational performance and health
      perspective to enhance the contribution of OT for this population's health
      related quality of life through meaningful PA.

PMID- 24302686
TI  - Can body mass index accurately predict adiposity in newborns?
AB  - Body mass index (BMI) is correlated with body fatness and risk of related
      diseases in children and adults. Proportionality indexes such as BMI and ponderal
      index (PI) have been suggested as complementary measures in neonatal growth
      assessment. Yet, they are still not used in neonates and their correlation with
      fatness is unknown. The aim of the study was to test the hypothesis that BMI z
      score would predict neonatal adiposity. Body composition measurements (ie, fat
      mass, fat-free mass) by air displacement plethysmography (PEA POD, LMI, Concord
      USA), weight and length were obtained in 200 infants >=36 weeks' gestational age
      (GA) at birth. Linear regression analysis showed a direct association between BMI
      z-score and %fat mass (r(2)=0.43, p<0.0001). This association was confirmed
      independently from sex, GA and maternal prepregnancy BMI. BMI z-score predicted
      adiposity better than PI. However, both BMI z-score and PI were poor predictors
      of adiposity at birth. 

PMID- 24302687
TI  - Early versus late enteral prophylactic iron supplementation in preterm very low
      birth weight infants: a randomised controlled trial.
AB  - OBJECTIVES: To evaluate whether preterm very low birth weight (VLBW) infants
      receiving early iron (EI) supplementation (2 mg/kg/day elemental iron) at 2 weeks
      postnatal age have improved serum ferritin levels compared with late iron (LI)
      supplementation at 6 weeks postnatal age. DESIGN: Single-blinded parallel-group
      interventional randomised controlled trial. SETTING: Tertiary care centre in
      southern India. INTERVENTIONS: Randomised at 2 weeks postnatal age to EI and LI
      groups and evaluated at 2, 6 and 12 weeks postnatal age. OUTCOME: The primary
      outcome was serum ferritin level at 12 weeks, and the secondary outcomes were the
      incidence of neonatal morbidities, haemoglobin level, anthropometric parameters
      and blood transfusion requirements. RESULTS: Of the 104 babies randomised,
      outcomes were analysed in 46 and 47 babies in EI and LI groups, respectively.
      Serum ferritin level was significantly higher (p<0.001) at 12 weeks (82+/-5 vs
      63+/-3 ng/mL) in the EI group. Haemoglobin (10.1+/-0.4 vs 9.2+/-0.4 g/dL) and
      mean corpuscular haemoglobin concentration (31+/-0.5 vs 29.4+/-0.5 g/dL) were
      also significantly (p<0.001) higher at 12 weeks in the EI group. There was a
      significant decrease of ferritin in the LI group and significant increase in
      ferritin in the EI group at 6 weeks compared with 2 weeks. There were no
      significant differences in the incidences of neonatal morbidities (necrotising
      enterocolitis, periventricular leukomalacia, retinopathy of prematurity),
      anthropometric parameters and blood transfusion requirements between the two
      groups. CONCLUSIONS: EI supplementation in preterm VLBW infants improves serum
      ferritin and haemoglobin levels. TRIAL REGISTRATION: CTRI/2013/01/003277.

PMID- 24302688
TI  - Modulation of feeding behavior by odorant-binding proteins in Drosophila
      melanogaster.
AB  - Nutrient intake and avoidance of toxins are essential for survival and controlled
      by attractive and aversive feeding responses. Drosophila melanogaster presents
      one of the best characterized systems for studies on chemosensation, which is
      mediated by multigene families of chemoreceptors, including olfactory receptors,
      gustatory receptors, and odorant-binding proteins (OBPs). Although the response
      profiles of gustatory receptors have been well studied, the contribution of OBPs
      to food intake is largely unknown. As most aversive ("bitter") tastants are
      hydrophobic, we hypothesized that OBPs may fulfill an essential function in
      transporting bitter tastants to gustatory receptors to modulate feeding behavior.
      Here, we used 16 RNAi lines that inhibit expression of individual target Obp
      genes and show that OBPs modulate sucrose intake in response to a panel of nine
      bitter compounds. Similar to their function in olfaction, OBPs appear to interact
      with bitter compounds in a combinatorial and sex-dependent manner. RNAi-mediated
      reduction in expression of individual Obp genes resulted either in enhanced or
      reduced intake of sucrose in the presence of bitter compounds, consistent with
      roles for OBPs in transporting tastants to bitter taste receptors, sequestering
      them to limit their access to these receptors, or interacting directly with
      gustatory neurons that respond to sucrose. 

PMID- 24302689
TI  - Effect of carbon dioxide in carbonated drinks on linguapalatal swallowing
      pressure.
AB  - This study aimed to investigate the influence of carbonated drinks with gas
      volumes (GV) of 0, 1.5, and 2.7 on linguapalatal swallowing pressure, intraoral
      carbonation perception, and maximum velocity of a bolus through the pharynx in
      healthy volunteers (N = 20, all female, age range; 20-21 years). The volunteers
      swallowed a 12-mL drink in the natural state. Linguapalatal swallowing pressure
      was measured using a special sensor sheet, and maximum velocity of the bolus
      through the pharynx was measured using ultrasonic diagnostic imaging equipment.
      Peak magnitude, integrated value, and duration of linguapalatal swallowing
      pressure and maximum velocity of a liquid bolus through the pharynx increased
      with an increase in carbon dioxide content in the carbonated drink. The total
      integrated values of carbonated drinks with GV of 1.5 and 2.7 were larger than
      that of the drink without carbon dioxide. These results suggest that the carbon
      dioxide dissolved in carbonated drinks influences the activity of taste receptors
      in the mouth and results in neuromotor responses. 

PMID- 24302690
TI  - Pregnancy does not affect human olfactory detection thresholds.
AB  - Hyperosmia is suspected in pregnancy; however, no empirical study using validated
      measures of olfactory function has clearly confirmed the anecdotal reports of
      this phenomenon. The goal of the current study is to compare the olfactory
      sensitivity of pregnant women to that of nonpregnant women and men. All
      participants rated their sense of smell and pregnant women listed the odors to
      which they were most sensitive. Detection thresholds were measured using a well
      validated protocol. A group of pregnant and nonpregnant women was studied
      longitudinally using a signal detection procedure designed to detect small
      differences in sensitivity. Pregnant women, particularly in the 1st trimester,
      rated their sense of smell to be higher than nonpregnant women and men and
      indicated many (primarily unpleasant) odors to which they were more sensitive.
      Women rated their sense of smell higher than men. However, there was no sex
      difference in thresholds and neither thresholds nor signal detection measures of
      sensitivity were significantly affected by either sex or pregnancy status. The
      implications of the lack of relationship between self-report and measures of
      olfactory sensitivity, particularly in pregnancy, are discussed. 

PMID- 24302691
TI  - New methods reveal oldest known fossil epiphyllous moss: Bryiidites utahensis
      gen. et sp. nov. (Bryidae).
AB  - PREMISE OF THE STUDY: Epiphyllous bryophytes are a highly characteristic feature
      of many humid tropical forest ecosystems. In contrast to the extensive fossil
      record for the leaves of their host plants, the record is virtually nonexistent
      for the epiphylls themselves, despite a fossil record for mosses that begins in
      the Middle Carboniferous Period, 330 million years ago. METHODS: Epifluorescence
      optical microscopy, scanning electron microscopy, and atomic force microscopy
      were employed to investigate an intimate association between a newly discovered
      epiphyllous moss and a Lauraceae plant host from the middle Cretaceous. KEY
      RESULTS: We describe the oldest fossil specimen of an epiphyllous moss,
      Bryiidites utahensis gen. et sp. nov., identified from an individual specimen
      only 450 um long, situated on an approximately one millimeter square fossil leaf
      fragment. The moss epiphyll is exquisitely preserved as germinating spores and
      short-celled protonemata with transverse and oblique cross-walls closely matching
      those of extant epiphyllous mosses on the surface of the plant-leaf hosts.
      CONCLUSIONS: The extension of the epiphyll record back to the middle Cretaceous
      provides fossil evidence for the appearance of epiphyllous mosses during the
      diversification of flowering plants, at least 95 million years ago. It also
      provides substantive evidence for a tropical maritime climate in central North
      America during the middle Cretaceous.

PMID- 24302692
TI  - Differential survival and growth of wild and cultivated seedlings of columnar
      cacti: Consequences of domestication.
AB  - PREMISE OF THE STUDY: Studies of domestication of cacti in the Tehuacan Valley
      have identified morphophysiological divergences between wild and cultivated
      populations. To determine whether such divergences are associated with
      differential survivorship in xeric and mesic environments characterizing wild and
      cultivated habitats, respectively, we hypothesized that seedlings from cultivated
      populations are less tolerant of xeric environments and that differences between
      wild and cultivated populations are greater in species with higher management
      intensity. METHODS: We compared size, survivorship, and absolute and relative
      growth rates (AGRs, RGRs) in shade and humidity gradients of seedlings from wild
      and cultivated populations of Stenocereus pruinosus, S. stellatus, Polaskia
      chichipe, and Escontria chiotilla. These species represent a range of management
      intensity, from highest to lowest, respectively. KEY RESULTS: Seedlings of
      cultivated populations were larger than those of wild populations in all species
      studied. The AGRs were significantly different in P. chichipe and E. chiotilla
      associated with management, whereas the RGRs and seedling survival were
      significantly different in S. pruinosus and P. chichipe throughout the shade
      gradient tested. We also found significant differences in seedling survival among
      humidity treatments in E. chiotilla and among shade treatments in P. chichipe.
      CONCLUSIONS: Artificial selection favoring larger fruits favors larger seeds and
      seedlings. Seedling survivorship and growth of managed plants are generally
      higher in mesic environments apparently because of natural selection associated
      with habitat conditions. Such differences may contribute to morphophysiological
      divergences between wild and cultivated populations. Interspecific differences
      might be associated with adaptations to the natural environments where each
      species occurs.

PMID- 24302693
TI  - Radiation and repeated transoceanic dispersal of Schoeneae (Cyperaceae) through
      the southern hemisphere.
AB  - PREMISE OF THE STUDY: The broad austral distribution of Schoeneae is almost
      certainly a product of long-distance dispersal. Owing to the inadequacies of
      existing phylogenetic data and a lack of rigorous biogeographic analysis,
      relationships within the tribe remain poorly resolved and its pattern of
      radiation and dispersal uncertain. We employed an expanded sampling of taxa and
      markers and a rigorous analytic approach to address these limitations. We
      evaluated the roles of geography and ecology in stimulating the initial radiation
      of the group and its subsequent dispersal across the southern hemisphere.
      METHODS: A dated tree was reconstructed using reversible-jump Markov chain Monte
      Carlo (MCMC) with a polytomy prior and molecular dating, applied to data from two
      nuclear and three cpDNA regions. Ancestral areas and habitats were inferred using
      dispersal-extinction-cladogenesis models. KEY RESULTS: Schoeneae originated in
      Australia in the Paleocene. The existence of a "hard" polytomy at the base of the
      clade reflects the rapid divergence of six principal lineages ca. 50 Ma, within
      Australia. From this ancestral area, Schoeneae have traversed the austral oceans
      with remarkable frequency, a total of 29 distinct dispersal events being reported
      here. Dispersal rates between landmasses are not explicable in terms of the
      geographical distances separating them. Transoceanic dispersal generally involved
      habitat stasis. CONCLUSIONS: Although the role of dispersal in explaining global
      distribution patterns is now widely accepted, the apparent ease with which such
      dispersal may occur has perhaps been under-appreciated. In Schoeneae,
      transoceanic dispersal has been remarkably frequent, with ecological opportunity,
      rather than geography, being most important in dictating dispersal patterns.

PMID- 24302694
TI  - Moss stomata in highly elaborated Oedipodium (Oedipodiaceae) and highly reduced
      Ephemerum (Pottiaceae) sporophytes are remarkably similar.
AB  - PREMISE OF THE STUDY: Mosses are central in understanding the origin,
      diversification, and early function of stomata in land plants. Oedipodium, the
      first extant moss with true stomata, has an elaborated capsule with numerous long
      pored stomata; in contrast, the reduced and short-lived Ephemerum has few round
      pored stomata. Here we present a comparative study of sporophyte anatomy and
      ultrastructure of stomata in two divergent mosses and its implications for
      stomata diversity and function. METHODS: Mature sporophytes of two moss species
      were studied using light, fluorescence, and scanning and transmission electron
      microscopy. Immunolocalization of pectin was conducted on Oedipodium using the
      LM19 antibody. KEY RESULTS: OEDIPODIUM capsules have extensive spongy tissue
      along the apophysis, whereas those of Ephemerum have minimal substomatal
      cavities. Stomatal ultrastructure and wall thickenings are highly similar.
      Sporophytes are covered by a cuticle that is thicker on guard cells and extends
      along walls surrounding the pore. Epicuticular waxes and pectin clog pores in old
      capsules. CONCLUSIONS: Ultrastructure of stomata in these mosses is similar to
      each other and less variable than that of tracheophytes. Anatomical features such
      as the presence of a cuticle, water-conducting cells, and spongy tissues with
      large areas for gas exchange are more pronounced in Oedipodium sporophytes and
      support the role of stomata in gas exchange and water transport during
      development and maturation. These features are modified in the reduced
      sporophytes of Ephemerum. Capsule anatomy coupled with the exclusive existence of
      stomata on capsules supports the concept that stomata in moss may also facilitate
      drying and dispersal of spores.

PMID- 24302695
TI  - A simple SDS-PAGE protein pattern from pitcher secretions as a new tool to
      distinguish Nepenthes species (Nepenthaceae).
AB  - PREMISE OF THE STUDY: Carnivorous plants have always fascinated scientists
      because these plants are able to attract, capture, and digest animal prey using
      their remarkable traps that contain digestive secretions. Nepenthes is one of the
      largest genera of carnivorous plants, with 120 species described thus far.
      Despite an outstanding diversity of trap designs, many species are often confused
      with each other and remain difficult to classify because they resemble pitchers
      or of the occurrence of interspecific hybrids. METHODS: Here, we propose a new
      method to easily distinguish Nepenthes species based on a SDS PAGE protein
      pattern analysis of their pitcher secretions. Intraspecific comparisons were
      performed among specimens growing in different environmental conditions to
      ascertain the robustness of this method. KEY RESULTS: Our results show that, at
      the juvenile stage and in the absence of prey in the pitcher, an examined species
      is characterized by a specific and stable profile, whatever the environmental
      conditions. CONCLUSIONS: The method we describe here can be used as a reliable
      tool to easily distinguish between Nepenthes species and to help with potential
      identification based on the species-specific protein pattern of their pitcher
      secretions, which is complementary to the monograph information.

PMID- 24302696
TI  - Representations of modality-specific affective processing for visual and auditory
      stimuli derived from functional magnetic resonance imaging data.
AB  - There is converging evidence that people rapidly and automatically encode
      affective dimensions of objects, events, and environments that they encounter in
      the normal course of their daily routines. An important research question is
      whether affective representations differ with sensory modality. This research
      examined the nature of the dependency of affect and sensory modality at a whole
      brain level of analysis in an incidental affective processing paradigm.
      Participants were presented with picture and sound stimuli that differed in
      positive or negative valence in an event-related functional magnetic resonance
      imaging experiment. Global statistical tests, applied at a level of the
      individual, demonstrated significant sensitivity to valence within modality, but
      not valence across modalities. Modality-general and modality-specific valence
      hypotheses predict distinctly different multidimensional patterns of the stimulus
      conditions. Examination of lower dimensional representation of the data
      demonstrated separable dimensions for valence processing within each modality.
      These results provide support for modality-specific valence processing in an
      incidental affective processing paradigm at a whole-brain level of analysis.
      Future research should further investigate how stimulus-specific emotional
      decoding may be mediated by the physical properties of the stimuli.

PMID- 24302697
TI  - Non-alcoholic fatty liver disease and hepatocellular carcinoma in a 7-year-old
      obese boy: coincidence or comorbidity?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) may develop from non-alcoholic fatty
      liver disease (NAFLD) either in the presence or in the absence of established
      cirrhosis. Non-cirrhotic patients with NAFLD-related HCC are usually adult, male
      and obese. However, this association has not been reported yet in younger age
      groups. Objectives In the present study, the clinical case of a 7-yaer-old obese
      boy with steatosis and HCC is presented. METHODS: A 7-year-old boy, with no
      evidence of chronic liver disease, was admitted for assessment of a liver mass.
      Preliminary assessment was suggestive of a combined and severe liver steatosis
      together with a malignant disease. RESULTS: A biopsy confirmed the suspected
      diagnosis of HCC; interestingly, the non-neoplastic liver was surrounded and
      characterized by the presence of steatosis and ballooning, and being absent of
      lobular inflammation and fibrosis. Chemotherapy and diet changes were conducted
      successfully with ultrasound characteristics suggesting improvements on both
      aspects: conventional liver mass resection could take place. CONCLUSIONS: This
      case report suggests that HCC might develop in paediatric age patients with
      obesity-related NAFLD, even in the absence of fibrosis.

PMID- 24302698
TI  - AstPT catalyses both reverse N1- and regular C2 prenylation of a methylated
      bisindolyl benzoquinone.
AB  - Prenylated bisindolyl benzoquinones exhibit interesting biological activities,
      such as antidiabetic or anti-HIV activities. A number of these compounds,
      including asterriquinones, have been isolated from Aspergillus terreus. In this
      study, we identified two putative genes by genome mining, ATEG_09980 and
      ATEG_00702, which share high sequence similarity with the known bisindolyl
      benzoquinone prenyltransferase TdiB from Aspergillus nidulans. The coding
      sequences were cloned and overexpressed in E. coli. The overproduced recombinant
      proteins were purified to near homogeneity and used for enzyme assays with
      asterriquinone D in the presence of dimethylallyl diphosphate. HPLC analysis
      showed that product formation was only detected in enzyme assays with EAU29429
      encoded by ATEG_09980, not in those with EAU39348 encoded by ATEG_00702. Product
      isolation and structure elucidation by NMR and MS analyses led to identification
      of N1-reversely and C2-regularly monoprenylated derivatives, as well as
      N1',N1''reversely, N1'-reversely, C2''-regularly diprenylated derivatives. This
      proved that EAU29429 functions as an asterriquinone prenyltransferase (AstPT) and
      indicated the involvement of EAU29429 rather than EAU39348 in the biosynthesis of
      methylated asterriquinones. Furthermore, incubation of monoprenylated enzyme
      products with AstPT resulted in the formation of the diprenylated derivatives. 

PMID- 24302699
TI  - Aphis (Hemiptera: Aphididae) species groups found in the Midwestern United States
      and their contribution to the phylogenetic knowledge of the genus.
AB  - A phylogeny of the genus Aphis Linnaeus, 1 758 was built primarily from specimens
      collected in the Midwest of the United States. A data matrix was constructed with
      68 species and 41 morphological characters with respective character states of
      alate and apterous viviparous females. Dendrogram topologies of analyses
      performed using UPGMA (Unweighted Pair Group Method with Arithmetic Mean),
      Maximum Parsimony and Bayesian analysis of Cytochrome Oxidase I, Elongation
      Factor 1-alpha and primary endosymbiont Buchnera aphidicola 16S sequences were
      not congruent. Bayesian analysis strongly supported most terminal nodes of the
      phylogenetic trees. The phylogeny was strongly supported by EF1-alpha, and
      analysis of COI and EF1-alpha molecular data combined with morphological
      characters. It was not supported by single analysis of COI or Buchnera aphidicola
      16S. Results from the Bayesian phylogeny show 4 main species groups: asclepiadis,
      fabae, gossypii, and middletonii. Results place Aphis and species of the genera
      Protaphis Borner, 1952, Toxoptera Koch, and Xerobion Nevsky, 1928 in a
      monophyletic clade. Morphological characters support this monophyly as well. The
      phylogeny shows that the monophyletic clade of the North American middletonii
      species group belong to the genus Protaphis: P. debilicornis (Gillette & Palmer,
      1929), comb. nov., P. echinaceae (Lagos and Voegtlin, 2009), comb. nov., and P.
      middletonii (Thomas, 1879). The genus Toxoptera should be considered a subgenus
      of Aphis (stat. nov.). The analysis also indicates that the current genus Iowana
      Frison, 1954 should be considered a subgenus of Aphis (stat. nov.).

PMID- 24302700
TI  - Treatment of "patellofemoral" cartilage lesions with matrix-assisted autologous
      chondrocyte transplantation: a comparison of patellar and trochlear lesions.
AB  - BACKGROUND: Matrix-assisted autologous chondrocyte transplantation (MACT) has
      been shown to offer good outcomes at midterm follow-up, but results are
      heterogeneous among different patients and lesion types. Being part of the same
      joint, both patellar and trochlear cartilage lesions are commonly considered to
      be affected by the same treatment issues, and therefore, it is common practice to
      report results obtained treating these lesions together. PURPOSE: To determine,
      in a large cohort of patients prospectively followed at midterm follow-up for
      patellofemoral chondral defects, if patellar and trochlear defects actually
      represent different clinical conditions with different healing potentials after
      cartilage treatment. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A
      total of 49 consecutive patients with full-thickness patellofemoral chondral
      lesions of the knee were treated with MACT at the authors' institute and followed
      prospectively for a minimum follow-up of 5 years. Among these 49 patients, 28
      were affected by patellar lesions, 17 were affected by trochlear lesions, and 4
      had both patellar and trochlear defects. The clinical outcome was analyzed with
      International Knee Documentation Committee (IKDC) subjective, EuroQol visual
      analogue scale (EQ-VAS), Kujala, and Tegner scores. RESULTS: A statistically
      significant improvement in all scores was observed after treatment. Patellar
      lesions required more realignment procedures and were more common in women. The
      comparative analysis showed better results for trochlear lesions compared with
      patellar lesions at all follow-ups, with mean IKDC scores at 5-year follow-up of
      89.6 +/- 12.7 and 69.7 +/- 17.6, respectively (P < .0005). Better results were
      also shown for the mean Kujala score (92.4 +/- 14.7 vs 81.5 +/- 12.7,
      respectively; P = .012) and mean EQ-VAS score (90.0 +/- 10.8 vs 81.9 +/- 11.7,
      respectively; P = .027). Finally, the sport activity level evaluated with the
      Tegner score confirmed the same trend; even though neither patellar nor trochlear
      lesion groups reached the preinjury level, both improved after treatment, with a
      significantly higher improvement in the trochlear lesion group (5.9 +/- 1.8 vs
      3.9 +/- 1.7, respectively; P < .0005). CONCLUSION: Patient characteristics differ
      between patellar and trochlear cartilage defects, and moreover, the results
      obtained are significantly different, with a markedly good outcome in cases with
      trochlear lesions and less satisfactory results for patients affected by
      cartilage lesions of the patella. Thus, patellar and trochlear defects should be
      considered separately when evaluating the outcome of cartilage treatments in this
      anatomic region.

PMID- 24302701
TI  - Methods for olfactory fMRI studies: Implication of respiration.
AB  - Human olfactory system is under-studied using fMRI compared with other sensory
      systems. Because the perception (intensity, threshold, and valence) and detection
      of odors are tightly involved with respiration, the subject's respiration pattern
      modulates and interacts with the experimental paradigm, which presents
      difficulties for olfactory fMRI data acquisition, post-processing, and
      interpretation. Based on our investigation on the interactions of odor
      presentation and subject's respiration, we propose a respiration-triggered event
      related olfactory fMRI technique and a data post-processing method that
      effectively captures precise onsets of olfactory blood-oxygen-level-dependent
      (BOLD) signal in the primary olfactory cortex. We compared the olfactory BOLD
      signals from seventeen normal healthy adults with diverse respiratory patterns
      and showed that the subjects' respiratory patterns modulated the olfactory
      stimulation paradigm, which significantly confounded the BOLD signal. The
      presented experimental technique provides a simple and effective means for
      generating reliable olfactory fMRI results.

PMID- 24302702
TI  - Identification of the first diphenyl ether gene cluster for pestheic acid
      biosynthesis in plant endophyte Pestalotiopsis fici.
AB  - The diphenyl ether pestheic acid was isolated from the endophytic fungus
      Pestalotiopsis fici, which is proposed to be the biosynthetic precursor of the
      unique chloropupukeananes. The pestheic acid biosynthetic gene (pta) cluster was
      identified in the fungus through genome scanning. Sequence analysis revealed that
      this gene cluster encodes a nonreducing polyketide synthase, a number of
      modification enzymes, and three regulators. Gene disruption and intermediate
      analysis demonstrated that the biosynthesis proceeded through formation of the
      polyketide backbone, cyclization of a polyketo acid to a benzophenone,
      chlorination, and formation of the diphenyl ether skeleton through oxidation and
      hydrolyzation. A dihydrogeodin oxidase gene, ptaE, was essential for diphenyl
      ether formation, and ptaM encoded a flavin-dependent halogenase catalyzing
      chlorination in the biosynthesis. Identification of the pta cluster laid the
      foundation to decipher the genetic and biochemical mechanisms involved in the
      pathway. 

PMID- 24302703
TI  - Reliability and validity of a Chinese version of the Diagnostic Interview for
      Borderlines-Revised.
AB  - INTRODUCTION: Borderline personality disorder (BPD) is the most studied of the
      axis II disorders. One of the most widely used diagnostic instruments is the
      Diagnostic Interview for Borderline Patients-Revised (DIB-R). The aim of this
      study was to test the reliability and validity of DIB-R for use in the Chinese
      culture. METHODS: The reliability and validity of the DIB-R Chinese version were
      assessed in a sample of 236 outpatients with a probable BPD diagnosis. The
      Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) was used
      as a standard. Test-retest reliability was tested six months later with 20
      patients, and inter-rater reliability was tested on 32 patients. RESULTS: The
      Chinese version of the DIB-R showed good internal global consistency (Cronbach's
      alpha of 0.916), good test-retest reliability (Pearson correlation of 0.704),
      good inter-rater reliability (intra-class correlation coefficient of 0.892 and
      kappa of 0.861). When compared with the DSM-IV diagnosis as measured by the SCID
      II, the DIB-R showed relatively good sensitivity (0.768) and specificity (0.891)
      at the cutoff of 7, moderate diagnostic convergence (kappa of 0.631), as well as
      good discriminating validity. DISCUSSION: The Chinese version of the DIB-R has
      good psychometric properties, which renders it a valuable method for examining
      the presence, the severity, and component phenotypes of BPD in Chinese samples.

PMID- 24302704
TI  - Prevalence and contributing factors to attention deficit hyperactivity disorder:
      a study of five- to fifteen-year-old children in Zhabei District, Shanghai.
AB  - INTRODUCTION: This work aims to understand the features among 5- to 15-year-old
      children with attention deficit hyperactivity disorder (ADHD) in Zhabei District
      in Shanghai. METHODS: Children with ADHD were studied using general background
      questionnaire, ADHD symptom rating questionnaire, and cluster-stratified
      sampling. A total of 9,900 valid questionnaires were utilized in this study. We
      conducted diagnostic interviews with suspected ADHD children and their parents
      using the criteria of the Diagnostic and Statistical Manual of Mental Disorders
      (4th Edition) for ADHD. RESULTS: The prevalence rate of ADHD among the children
      was 4.6%, of which 2.4%, 0.4%, and 1.8% had ADHD-I ADHD-HI, and ADHD-C types,
      respectively. The prevalence rates in boys and girls were 6.6% and 2.7% (ratio,
      2.41 : 1), respectively. Significant differences in prevalence rate were found
      among children with different age groups and ADHD types. Children aged 7-10 years
      had the highest prevalence rate (6.3%). Externally, residence children had higher
      prevalence than local residents. Significant differences in prevalence rate were
      also found among children with parents having different educational and
      socioeconomic level. DISCUSSION: The prevalence of ADHD-HI was higher than the
      other two types. The highest prevalence was observed in 7- to 10-year-old
      children. The influential factors of ADHD prevalence were age, gender, and
      educational level.

PMID- 24302705
TI  - Change of psychological distress and physical disability in patients with
      rheumatoid arthritis over the last two decades.
AB  - OBJECTIVE: During the past decades, a more cautious approach with respect to
      prescribing medication and physical exercise progressed toward evidence-based
      guidelines regarding the management of rheumatoid arthritis (RA). Currently,
      physical activity and other means to improve well-being and functioning are
      encouraged, and the disease is targeted earlier with more intensive and
      aggressive pharmacologic treatment. The current study examined whether
      psychological distress and physical disability in patients with RA reduced over
      the last 2 decades and whether this is explained by a reduction of disease
      activity. METHODS: From 1990-2011, consecutive patients with RA (n = 1,151, age
      range 17-86 years, 68% female, 62% rheumatoid factor positive) were monitored at
      diagnosis and after 3-5 years of treatment (followup). Depressed mood, anxiety,
      and physical disability were predicted in multiple linear regression analyses by
      year of assessment, disease activity, and patient demographics. RESULTS: Over the
      decades, depressed mood (P = 0.01), anxiety (P = 0.001), and physical disability
      (P = 0.02) reduced at diagnosis and within-treatment improvement of anxiety (P =
      0.04) and physical disability (P < 0.001) increased. Percentages of patients with
      depressed mood, anxiety, and physical disability at followup changed from 25%,
      23%, and 53%, respectively, 2 decades ago to 14%, 12%, and 31%, respectively,
      currently. After taking account of reduction in disease activity, the decrease in
      physical disability remained significant (P < 0.001). CONCLUSION: Over the last 2
      decades, psychological distress and physical disability decreased. This favorable
      trend might partly be due to reduced disease activity. The results indicate that
      patients with RA have a better opportunity to live a valued life currently than
      20 years ago.

PMID- 24302706
TI  - Discordance of global estimates by patients and their physicians in usual care of
      many rheumatic diseases: association with 5 scores on a Multidimensional Health
      Assessment Questionnaire (MDHAQ) that are not found on the Health Assessment
      Questionnaire (HAQ).
AB  - OBJECTIVE: To analyze discordance between global estimates by patients (PATGL)
      and their physicians (DOCGL) according to demographic and self-report variables
      on a Multidimensional Health Assessment Questionnaire (MDHAQ) in patients with
      many rheumatic diseases seen in usual care. METHODS: Each patient completed an
      MDHAQ at each visit, which includes scores for physical function, pain, and
      PATGL, each found on the traditional Health Assessment Questionnaire (HAQ), and
      scores for sleep quality, anxiety, depression, self-report joint count, and
      fatigue, which are not found on the HAQ. A random visit of 980 patients with any
      rheumatic diagnosis was analyzed in 3 categories: PATGL=DOCGL (within 2 of 10
      units), PATGL>DOCGL (by >=2 of 10 units), and DOCGL>PATGL (by >=2 of 10 units),
      using descriptive statistics and multinomial logistic regression models. RESULTS:
      Patients included 145 with rheumatoid arthritis, 57 with systemic lupus
      erythematosus, 173 with osteoarthritis, 348 with other inflammatory diseases, and
      257 with other noninflammatory diseases. Overall, PATGL=DOCGL in 509 (52%),
      PATGL>DOCGL in 371 (38%), and DOCGL>PATGL in 100 (10%). PATGL>DOCGL was
      associated significantly with older age, female sex, low formal education,
      Hispanic ethnicity, not working, high MDHAQ physical function and pain scores,
      and high scores for fatigue, poor sleep, anxiety, depression, and self-report
      joint count, which are not available on the HAQ. Pain and fatigue were
      significant in a final multinomial logistic regression; the other variables may
      raise awareness of discordance to clinicians. CONCLUSION: Global estimates of
      patients indicated significantly poorer status than estimates of their physicians
      in 38% of 980 patients with rheumatic conditions, and were associated with
      demographic and MDHAQ scores, 5 of which are not available on the HAQ.

PMID- 24302707
TI  - Induced pluripotent stem cells: origins, applications, and future perspectives.
AB  - Embryonic stem (ES) cells are widely used for different purposes, including gene
      targeting, cell therapy, tissue repair, organ regeneration, and so on. However,
      studies and applications of ES cells are hindered by ethical issues regarding
      cell sources. To circumvent ethical disputes, great efforts have been taken to
      generate ES cell-like cells, which are not derived from the inner cell mass of
      blastocyst-stage embryos. In 2006, Yamanaka et al. first reprogrammed mouse
      embryonic fibroblasts into ES cell-like cells called induced pluripotent stem
      (iPS) cells. About one year later, Yamanaka et al. and Thomson et al.
      independently reprogrammed human somatic cells into iPS cells. Since the first
      generation of iPS cells, they have now been derived from quite a few different
      kinds of cell types. In particular, the use of peripheral blood facilitates
      research on iPS cells because of safety, easy availability, and plenty of cell
      sources. Now iPS cells have been used for cell therapy, disease modeling, and
      drug discovery. In this review, we describe the generations, applications,
      potential issues, and future perspectives of iPS cells. 

PMID- 24302708
TI  - Influence of heat stress on leaf ultrastructure, photosynthetic performance, and
      ascorbate peroxidase gene expression of two pear cultivars (Pyrus pyrifolia).
AB  - Plants encounter a variety of stresses in natural environments. One-year-old pot
      grown trees of pear (Pyrus pyrifolia Nakai cv. Cuiguan and Wonhwang) were exposed
      to two heat stress regimes. Under constant short-term heat stress, chloroplasts
      and mitochondria were visibly damaged. Relative chlorophyll content and maximum
      photochemical efficiency of photosystem II were significantly decreased, which
      indicated that the leaf photosynthetic capability declined. Under chronic heat
      stress, mesophyll cell ultrastructure was not obviously damaged, but leaf
      photosynthetic capability was still restrained. As chronic heat stress was a
      simulation of the natural environment in summer, further study of the responses
      under this stress regime was undertaken. Ascorbate peroxidase (APX) activity was
      increased in 'Cuiguan', but not in 'Wonhwang'. Inducible expression of PpAPX
      genes in the cytoplasm, chloroplasts and peroxisomes was consistent with
      increased APX activity in 'Cuiguan', whereas only weak induction of PpAPX genes
      was observed in 'Wonhwang'. The isoenzymes cytosolic APX1 (cAPX1) and stromal APX
      (sAPX) were confirmed to be localized in the cytoplasm and chloroplasts,
      respectively.

PMID- 24302709
TI  - Fungal diversity in adult date palm (Phoenix dactylifera L.) revealed by culture
      dependent and culture-independent approaches.
AB  - Endophytic flora plays a vital role in the colonization and survival of host
      plants, especially in harsh environments, such as arid regions. This flora may,
      however, contain pathogenic species responsible for various troublesome host
      diseases. The present study is aimed at investigating the diversity of both
      cultivable and non-cultivable endophytic fungal floras in the internal tissues
      (roots and leaves) of Tunisian date palm trees (Phoenix dactylifera).
      Accordingly, 13 isolates from both root and leaf samples, exhibiting distinct
      colony morphology, were selected from potato dextrose agar (PDA) medium and
      identified by a sequence match search wherein their 18S-28S internal transcribed
      spacer (ITS) sequences were compared to those available in public databases.
      These findings revealed that the cultivable root and leaf isolates fell into two
      groups, namely Nectriaceae and Pleosporaceae. Additionally, total DNA from palm
      roots and leaves was further extracted and ITS fragments were amplified.
      Restriction fragment length polymorphism (RFLP) analysis of the ITS from 200
      fungal clones (leaves: 100; roots: 100) using HaeIII restriction enzyme revealed
      13 distinct patterns that were further sequenced and led to the identification of
      Alternaria, Cladosporium, Davidiella (Cladosporium teleomorph), Pythium,
      Curvularia, and uncharacterized fungal endophytes. Both approaches confirmed that
      while the roots were predominantly colonized by Fusaria (members of the
      Nectriaceae family), the leaves were essentially colonized by Alternaria (members
      of the Pleosporaceae family). Overall, the findings of the present study
      constitute, to the authors' knowledge, the first extensive report on the
      diversity of endophytic fungal flora associated with date palm trees (P.
      dactylifera). 

PMID- 24302710
TI  - Genetic variation in alkaloid accumulation in leaves of Nicotiana.
AB  - Alkaloids are plant secondary metabolites that are widely distributed in
      Nicotiana species and contribute greatly to the quality of tobacco leaves. Some
      alkaloids, such as nornicotine and myosmine, have adverse effects on human
      health. To reduce the content of harmful alkaloids in tobacco leaves through
      conventional breeding, a genetic study of the alkaloid variation among different
      genotypes is required. In this study, alkaloid profiles in leaves of five
      Nicotiana tabacum cultivars and Nicotiana tomentosiformis were investigated. Six
      alkaloids were identified from all six genotypes via gas chromatograph-mass
      spectrometry (GC-MS). Significant differences in alkaloid content were observed
      both among different leaf positions and among cultivars. The contents of
      nornicotine and myosmine were positively and significantly correlated
      (R(2)=0.881), and were also separated from those of other alkaloids by
      clustering. Thus, the genotype plays a major role in alkaloid accumulation,
      indicating a high potential for manipulation of alkaloid content through
      traditional breeding. 

PMID- 24302711
TI  - Cloning and functional analysis of a novel ascorbate peroxidase (APX) gene from
      Anthurium andraeanum.
AB  - An 888-bp full-length ascorbate peroxidase (APX) complementary DNA (cDNA) gene
      was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110
      bp 5'-noncoding region, a 28-bp 3'-noncoding region, and a 750-bp open reading
      frame (ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its
      structure consisting of alpha-helixes, beta-turns, and random coils. The AnAPX
      protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from
      Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis
      guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non
      significantly in roots, stems, leaves, spathes, and spadices by real-time
      polymerase chain reaction (RT-PCR) analysis. Interestingly, this gene expression
      was remarkably up-regulated in response to a cold stress under 6  degrees C,
      implying that AnAPX might play an important role in A. andraeanum tolerance to
      cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by
      transformation with an AnAPX expression construct driven by CaMV 35S promoter.
      The transformed tobacco seedlings under 4  degrees C showed less electrolyte
      leakage (EL) and malondialdehyde (MDA) content than the control. The content of
      MDA was correlated with chilling tolerance in these transgenic plants. These
      results show that AnAPX can prevent the chilling challenged plant from cell
      membrane damage and ultimately enhance the plant cold tolerance.

PMID- 24302712
TI  - Involvement of phosphatidate phosphatase in the biosynthesis of triacylglycerols
      in Chlamydomonas reinhardtii.
AB  - Lipid biosynthesis is essential for eukaryotic cells, but the mechanisms of the
      process in microalgae remain poorly understood. Phosphatidic acid
      phosphohydrolase or 3-sn-phosphatidate phosphohydrolase (PAP) catalyzes the
      dephosphorylation of phosphatidic acid to form diacylglycerols and inorganic
      orthophosphates. This reaction is integral in the synthesis of triacylglycerols.
      In this study, the mRNA level of the PAP isoform CrPAP2 in a species of
      Chlamydomonas was found to increase in nitrogen-free conditions. Silencing of the
      CrPAP2 gene using RNA interference resulted in the decline of lipid content by
      2.4%-17.4%. By contrast, over-expression of the CrPAP2 gene resulted in an
      increase in lipid content by 7.5%-21.8%. These observations indicate that
      regulation of the CrPAP2 gene can control the lipid content of the algal cells.
      In vitro CrPAP2 enzyme activity assay indicated that the cloned CrPAP2 gene
      exhibited biological activities.

PMID- 24302713
TI  - Morphological and biochemical responses of Oryza sativa L. (cultivar MR219) to
      ion beam irradiation.
AB  - OBJECTIVE: Heavy ion beam, which has emerged as a new mutagen in the mutation
      breeding of crops and ornamental plants, is expected to result in the induction
      of novel mutations. This study investigates the morphological and biochemical
      responses of Oryza sativa toward different doses of carbon ion beam irradiation.
      METHODS: In this study, the dry seeds of O. sativa were irradiated at 0, 20, 40,
      60, 80, 100, and 120 Gy, followed by in-vitro germination under controlled
      conditions. Morphological and biochemical studies were conducted to investigate
      the morphological and physiological responses of O. sativa towards ion beam
      irradiation. RESULTS: The study demonstrated that low doses (10 Gy) of ion beam
      have a stimulating effect on the height, root length, and fresh weight of the
      plantlets but not on the number of leaves. Meanwhile, doses higher than 10 Gy
      caused reductions in all the morphological parameters studied as compared to the
      control samples. The highest total soluble protein content [(2.11 +/- 0.47) mg/g
      FW] was observed in plantlets irradiated at 20 Gy. All irradiated plantlets were
      found to have 0.85% to 58.32% higher specific activity of peroxidase as compared
      to the control samples. The present study also revealed that low doses of ion
      beam (10 and 20 Gy) had negligible effect on the total chlorophyll content of O.
      sativa plantlets while 40 Gy had a stimulating effect on the chlorophyll content.
      Plantlets irradiated between 40 to 120 Gy were shown to be 0.38% to 9.98% higher
      in total soluble nitrogen content which, however, was not significantly different
      from the control samples. CONCLUSIONS: Carbon ion beam irradiation administered
      at low to moderate doses of 10 to 40 Gy may induce O. sativa mutants with
      superior characteristics.

PMID- 24302714
TI  - Accumulation of mercury in rice grain and cabbage grown on representative Chinese
      soils.
AB  - A pot culture experiment was carried out to investigate the accumulation
      properties of mercury (Hg) in rice grain and cabbage grown in seven soil types
      (Udic Ferrisols, Mollisol, Periudic Argosols, Latosol, Ustic Cambosols, Calcaric
      Regosols, and Stagnic Anthrosols) spiked with different concentrations of Hg (CK,
      0.25, 0.50, 1.00, 2.00, and 4.00 mg/kg). The results of this study showed that Hg
      accumulation of plants was significantly affected by soil types. Hg concentration
      in both rice grain and cabbage increased with soil Hg concentrations, but this
      increase differed among the seven soils. The stepwise multiple regression
      analysis showed that pH, Mn(II), particle size distribution, and cation exchange
      capacity have a close relationship with Hg accumulation in plants, which
      suggested that physicochemical characteristics of soils can affect the Hg
      accumulation in rice grain and cabbage. Critical Hg concentrations in seven soils
      were identified for rice grain and cabbage based on the maximum safe level for
      daily intake of Hg, dietary habits of the population, and Hg accumulation in
      plants grown in different soil types. Soil Hg limits for rice grain in Udic
      Ferrisols, Mollisol, Periudic Argosols, Latosol, Ustic Cambosols, Calcaric
      Regosols, and Stagnic Anthrosols were 1.10, 2.00, 2.60, 2.78, 1.53, 0.63, and
      2.17 mg/kg, respectively, and critical soil Hg levels for cabbage are 0.27, 1.35,
      1.80, 1.70, 0.69, 1.68, and 2.60 mg/kg, respectively. 

PMID- 24302715
TI  - Sorption of ammonium and phosphate from aqueous solution by biochar derived from
      phytoremediation plants.
AB  - The study on biochar derived from plant biomass for environmental applications is
      attracting more and more attention. Twelve sets of biochar were obtained by
      treating four phytoremediation plants, Salix rosthornii Seemen, Thalia dealbata,
      Vetiveria zizanioides, and Phragmites sp., sequentially through pyrolysis at 500 
      degrees C in a N2 environment, and under different temperatures (500, 600, and
      700  degrees C) in a CO2 environment. The cation exchange capacity and specific
      surface area of biochar varied with both plant species and pyrolysis temperature.
      The magnesium (Mg) content of biochar derived from T. dealbata (TC) was obviously
      higher than that of the other plant biochars. This biochar also had the highest
      sorption capacity for phosphate and ammonium. In terms of biomass yields,
      adsorption capacity, and energy cost, T. dealbata biochar produced at 600 
      degrees C (TC600) is the most promising sorbent for removing contaminants (N and
      P) from aqueous solution. Therefore, T. dealbata appears to be the best candidate
      for phytoremediation application as its biomass can make a good biochar for
      environmental cleaning. 

PMID- 24302716
TI  - Atrazine biodegradation efficiency, metabolite detection, and trzD gene
      expression by enrichment bacterial cultures from agricultural soil.
AB  - Atrazine is a selective herbicide used in agricultural fields to control the
      emergence of broadleaf and grassy weeds. The persistence of this herbicide is
      influenced by the metabolic action of habituated native microorganisms. This
      study provides information on the occurrence of atrazine mineralizing bacterial
      strains with faster metabolizing ability. The enrichment cultures were tested for
      the biodegradation of atrazine by high-performance liquid chromatography (HPLC)
      and mass spectrometry. Nine cultures JS01.Deg01 to JS09.Deg01 were identified as
      the degrader of atrazine in the enrichment culture. The three isolates
      JS04.Deg01, JS07.Deg01, and JS08.Deg01 were identified as efficient atrazine
      metabolizers. Isolates JS04.Deg01 and JS07.Deg01 produced hydroxyatrazine (HA) N
      isopropylammelide and cyanuric acid by dealkylation reaction. The isolate
      JS08.Deg01 generated deethylatrazine (DEA), deisopropylatrazine (DIA), and
      cyanuric acid by N-dealkylation in the upper degradation pathway and later it
      incorporated cyanuric acid in their biomass by the lower degradation pathway. The
      optimum pH for degrading atrazine by JS08.Deg01 was 7.0 and 16S rDNA phylogenetic
      typing identified it as Enterobacter cloacae strain JS08.Deg01. The highest
      atrazine mineralization was observed in case of isolate JS08.Deg01, where an
      ample amount of trzD mRNA was quantified at 72 h of incubation with atrazine.
      Atrazine bioremediating isolate E. cloacae strain JS08.Deg01 could be the better
      environmental remediator of agricultural soils and the crop fields contaminated
      with atrazine could be the source of the efficient biodegrading microbial strains
      for the environmental cleanup process.

PMID- 24302717
TI  - Designer aminoglycosides that selectively inhibit cytoplasmic rather than
      mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment
      of genetic diseases.
AB  - There is compelling evidence that aminoglycoside (AG) antibiotics can induce the
      mammalian ribosome to suppress disease-causing nonsense mutations and partially
      restore the expression of functional proteins. However, prolonged AG treatment
      can cause detrimental side effects in patients, including most prominently,
      ototoxicity. Recent mechanistic discussions have considered the relative
      contributions of mitochondrial and cytoplasmic protein synthesis inhibition to AG
      induced ototoxicity. We show that AGs inhibit mitochondrial protein synthesis in
      mammalian cells and perturb cell respiration, leading to a time- and dose
      dependent increase in superoxide overproduction and accumulation of free ferrous
      iron in mitochondria caused by oxidative damage of mitochondrial aconitase,
      ultimately leading to cell apoptosis via the Fenton reaction. These deleterious
      effects increase with the increased potency of AG to inhibit the mitochondrial
      rather than cytoplasmic protein synthesis, which in turn correlates with their
      ototoxic potential in both murine cochlear explants and the guinea pig in vivo.
      The deleterious effects of AGs were alleviated in synthetic derivatives specially
      designed for the treatment of genetic diseases caused by nonsense mutations and
      possessing low affinity toward mitochondrial ribosomes. This work highlights the
      benefit of a mechanism-based drug redesign strategy that can maximize the
      translational value of "readthrough therapy" while mitigating drug-induced side
      effects. This approach holds promise for patients suffering from genetic diseases
      caused by nonsense mutations. 

PMID- 24302718
TI  - Coherence between cellular responses and in vitro splicing inhibition for the
      anti-tumor drug pladienolide B and its analogs.
AB  - Pladienolide B (PB) is a potent cancer cell growth inhibitor that targets the
      SF3B1 subunit of the spliceosome. There is considerable interest in the compound
      as a potential chemotherapeutic, as well as a tool to study SF3B1 function in
      splicing and cancer development. The molecular structure of PB, a bacterial
      natural product, contains a 12-member macrolide ring with an extended epoxide
      containing side chain. Using a novel concise enantioselective synthesis, we
      created a series of PB structural analogs and the structurally related compound
      herboxidiene. We show that two methyl groups in the PB side chain, as well as a
      feature of the macrolide ring shared with herboxidiene, are required for splicing
      inhibition in vitro. Unexpectedly, we find that the epoxy group contributes only
      modestly to PB potency and is not absolutely necessary for activity. The
      orientations of at least two chiral centers off the macrolide ring have no effect
      on PB activity. Importantly, the ability of analogs to inhibit splicing in vitro
      directly correlated with their effects in a series of cellular assays. Those
      effects likely arise from inhibition of some, but not all, endogenous splicing
      events in cells, as previously reported for the structurally distinct SF3B1
      inhibitor spliceostatin A. Together, our data support the idea that the impact of
      PB on cells is derived from its ability to impair the function of SF3B1 in
      splicing and also demonstrate that simplification of the PB scaffold is feasible.

PMID- 24302719
TI  - The role of diacylglycerol kinase zeta and phosphatidic acid in the mechanical
      activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle
      hypertrophy.
AB  - The activation of mTOR signaling is essential for mechanically induced changes in
      skeletal muscle mass, and previous studies have suggested that mechanical stimuli
      activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D
      (PLD)-dependent increase in the concentration of phosphatidic acid (PA).
      Consistent with this conclusion, we obtained evidence which further suggests that
      mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling.
      Unexpectedly though, we found that the activation of PLD is not necessary for the
      mechanically induced increases in PA or mTOR signaling. Motivated by this
      observation, we performed experiments that were aimed at identifying the
      enzyme(s) that promotes the increase in PA. These experiments revealed that
      mechanical stimulation increases the concentration of diacylglycerol (DAG) and
      the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using
      knock-out mice, we determined that the zeta isoform of DGK (DGKzeta) is necessary
      for the mechanically induced increase in PA. We also determined that DGKzeta
      significantly contributes to the mechanical activation of mTOR signaling, and
      this is likely driven by an enhanced binding of PA to mTOR. Last, we found that
      the overexpression of DGKzeta is sufficient to induce muscle fiber hypertrophy
      through an mTOR-dependent mechanism, and this event requires DGKzeta kinase
      activity (i.e. the synthesis of PA). Combined, these results indicate that
      DGKzeta, but not PLD, plays an important role in mechanically induced increases
      in PA and mTOR signaling. Furthermore, this study suggests that DGKzeta could be
      a fundamental component of the mechanism(s) through which mechanical stimuli
      regulate skeletal muscle mass. 

PMID- 24302720
TI  - Multiple roles of the SO4(2-)/Cl-/OH- exchanger protein Slc26a2 in chondrocyte
      functions.
AB  - Mutations in the SO4(2-)/Cl(-)/OH(-) exchanger Slc26a2 cause the disease
      diastrophic dysplasia (DTD), resulting in aberrant bone development and,
      therefore, skeletal deformities. DTD is commonly attributed to a lack of
      chondrocyte SO4(2-) uptake and proteoglycan sulfation. However, the skeletal
      phenotype of patients with DTD is typified by reduction in cartilage and
      osteoporosis of the long bones. Chondrocytes of patients with DTD are irregular
      in size and have a reduced capacity for proliferation and terminal
      differentiation. This raises the possibility of additional roles for Slc26a2 in
      chondrocyte function. Here, we examined the roles of Slc26a2 in chondrocyte
      biology using two distinct systems: mouse progenitor mesenchymal cells
      differentiated to chondrocytes and freshly isolated mouse articular chondrocytes
      differentiated into hypertrophic chondrocytes. Slc26a2 expression was manipulated
      acutely by delivery of Slc26a2 or shSlc26a2 with lentiviral vectors. We
      demonstrate that slc26a2 is essential for chondrocyte proliferation and
      differentiation and for proteoglycan synthesis. Slc26a2 also regulates the
      terminal stage of chondrocyte cell size expansion. These findings reveal multiple
      roles for Slc26a2 in chondrocyte biology and emphasize the importance of Slc26a2
      mediated protein sulfation in cell signaling, which may account for the complex
      phenotype of DTD. 

PMID- 24302721
TI  - Phosphorylation of CEACAM1 molecule by calmodulin kinase IID in a three
      dimensional model of mammary gland lumen formation.
AB  - Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), a
      transmembrane protein, expressed on normal breast epithelial cells is down
      regulated in breast cancer. Phosphorylation of Thr-457 on the short cytoplasmic
      domain isoform (CEACAM1-SF) that is predominant in normal epithelial cells is
      required for lumen formation in a three-dimensional model that involves apoptosis
      of the central acinar cells. Calmodulin kinase IID (CaMKIID) was selected as a
      candidate for the kinase required for Thr-457 phosphorylation from a gene chip
      analysis comparing genes up-regulated in MCF7 cells expressing wild type CEACAM1
      SF compared with the T457A-mutated gene (Chen, C. J., Kirshner, J., Sherman, M.
      A., Hu, W., Nguyen, T., and Shively, J. E. (2007) J. Biol. Chem. 282, 5749-5760).
      Up-regulation of CaMKIID during lumen formation was confirmed by analysis of mRNA
      and protein levels. CaMKIID was able to phosphorylate a synthetic peptide
      corresponding to the cytoplasmic domain of CEACAM1-SF and was covalently bound to
      biotinylated and T457C-modified peptide in the presence of a kinase trap
      previously described by Shokat and co-workers (Maly, D. J., Allen, J. A., and
      Shokat, K. M. (2004) J. Am. Chem. Soc. 126, 9160-9161). When cell lysates from
      wild type-transfected MCF7 cells undergoing lumen formation were incubated with
      the peptide and kinase trap, a cross-linked band corresponding to CaMKIID was
      observed. When these cells were treated with an RNAi that inhibits CaMKIID
      expression, lumen formation was blocked by over 90%. We conclude that CaMKIID
      specifically phosphorylates Thr-457 on CEACAM1-SF, which in turn regulates the
      process of lumen formation via apoptosis of the central acinar cells. 

PMID- 24302722
TI  - Gap junction intercellular communication mediated by connexin43 in astrocytes is
      essential for their resistance to oxidative stress.
AB  - Oxidative stress induced by reactive oxygen species (ROS) is associated with
      various neurological disorders including aging, neurodegenerative diseases, as
      well as traumatic and ischemic insults. Astrocytes have an important role in the
      anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43)
      forms intercellular channels as well as hemichannels in astrocytes. In the
      present study, we investigated the contribution of Cx43 to astrocytic death
      induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43
      exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted
      in increased ROS-induced astrocytic death, supporting a cell protective effect of
      functional Cx43 channels. H2O2 transiently increased hemichannel activity, but
      reduced gap junction intercellular communication (GJIC). GJIC in wild-type
      astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes.
      Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel
      activity, indicating the presence of other hemichannel proteins. Panx1, which is
      predicted to be a major hemichannel contributor in astrocytes, did not appear to
      have any cell protective effect from H2O2 insults. Our data suggest that GJIC is
      important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation,
      H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total
      Cx43 level. Cx43 has been reported to promote astrocytic death induced by
      hypoxia/reoxygenation. We therefore speculate the increase in Cx43
      dephosphorylation may account for the facilitation of astrocytic death. Our
      findings suggest that the role of Cx43 in response to cellular stress is
      dependent on the activation of signaling pathways leading to alteration of Cx43
      phosphorylation states. 

PMID- 24302723
TI  - A novel acidic matrix protein, PfN44, stabilizes magnesium calcite to inhibit the
      crystallization of aragonite.
AB  - Magnesium is widely used to control calcium carbonate deposition in the shell of
      pearl oysters. Matrix proteins in the shell are responsible for nucleation and
      growth of calcium carbonate crystals. However, there is no direct evidence
      supporting a connection between matrix proteins and magnesium. Here, we
      identified a novel acidic matrix protein named PfN44 that affected aragonite
      formation in the shell of the pearl oyster Pinctada fucata. Using immunogold
      labeling assays, we found PfN44 in both the nacreous and prismatic layers. In
      shell repair, PfN44 was repressed, whereas other matrix proteins were up
      regulated. Disturbing the function of PfN44 by RNAi led to the deposition of
      porous nacreous tablets with overgrowth of crystals in the nacreous layer. By in
      vitro circular dichroism spectra and fluorescence quenching, we found that PfN44
      bound to both calcium and magnesium with a stronger affinity for magnesium.
      During in vitro calcium carbonate crystallization and calcification of amorphous
      calcium carbonate, PfN44 regulated the magnesium content of crystalline carbonate
      polymorphs and stabilized magnesium calcite to inhibit aragonite deposition.
      Taken together, our results suggested that by stabilizing magnesium calcite to
      inhibit aragonite deposition, PfN44 participated in P. fucata shell formation.
      These observations extend our understanding of the connections between matrix
      proteins and magnesium. 

PMID- 24302724
TI  - Non-growing Rhodopseudomonas palustris increases the hydrogen gas yield from
      acetate by shifting from the glyoxylate shunt to the tricarboxylic acid cycle.
AB  - When starved for nitrogen, non-growing cells of the photosynthetic bacterium
      Rhodopseudomonas palustris continue to metabolize acetate and produce H2, an
      important industrial chemical and potential biofuel. The enzyme nitrogenase
      catalyzes H2 formation. The highest H2 yields are obtained when cells are
      deprived of N2 and thus use available electrons to synthesize H2 as the exclusive
      product of nitrogenase. To understand how R. palustris responds metabolically to
      increase H2 yields when it is starved for N2, and thus not growing, we tracked
      changes in biomass composition and global transcript levels. In addition to a 3.5
      fold higher H2 yield by non-growing cells we also observed an accumulation of
      polyhydroxybutyrate to over 30% of the dry cell weight. The transcriptome of R.
      palustris showed down-regulation of biosynthetic processes and up-regulation of
      nitrogen scavenging mechanisms in response to N2 starvation but gene expression
      changes did not point to metabolic activities that could generate the reductant
      necessary to explain the high H2 yield. We therefore tracked (13)C-labeled
      acetate through central metabolic pathways. We found that non-growing cells
      shifted their metabolism to use the tricarboxylic acid cycle to metabolize
      acetate in contrast to growing cells, which used the glyoxylate cycle
      exclusively. This shift enabled cells to more fully oxidize acetate, providing
      the necessary reducing power to explain the high H2 yield. 

PMID- 24302725
TI  - Acetylation at lysine 183 of progesterone receptor by p300 accelerates DNA
      binding kinetics and transactivation of direct target genes.
AB  - The identification of lysine acetylation of steroid hormone receptors has
      previously been based on the presence of consensus motif (K/R)XKK. This study
      reports the discovery by mass spectrometry of a novel progesterone receptor
      acetylation site at Lys-183 that is not in the consensus motif. In vivo
      acetylation and mutagenesis experiments revealed that Lys-183 is a primary site
      of progesterone receptor (PR) acetylation. Lys-183 acetylation is enhanced by
      p300 overexpression and abrogated by p300 gene silencing, suggesting that p300 is
      the major acetyltransferase for Lys-183 acetylation. Furthermore, p300-mediated
      Lys-183 acetylation is associated with heightened PR activity. Accordingly, the
      acetylation-mimicking mutant PRB-K183Q exhibited accelerated DNA binding kinetics
      and greater activity compared with the wild-type PRB on genes containing
      progesterone response element. In contrast, Lys-183 acetylation had no influence
      on PR tethering effect on the nuclear factor kappa-light chain enhancer of
      activated B cells (NFkappaB). Additionally, increases of Lys-183 acetylation by
      p300 overexpression or inhibition of deacetylation resulted in increases of Ser
      294 phosphorylation levels. In conclusion, PR acetylation at Lys-183 by p300
      potentiates PR activity through accelerated binding of its direct target genes
      without affecting PR tethering on other transcription factors. The effect may be
      mediated by enhancing Ser-294 phosphorylation. 

PMID- 24302726
TI  - Sympathetic activation induces skeletal Fgf23 expression in a circadian rhythm
      dependent manner.
AB  - The circadian clock network is well known to link food intake and metabolic
      outputs. Phosphorus is a pivotal nutritional factor involved in energy and
      skeletal metabolisms and possesses a circadian profile in the circulation;
      however, the precise mechanisms whereby phosphate metabolism is regulated by the
      circadian clock network remain largely unknown. Because sympathetic tone, which
      displays a circadian profile, is activated by food intake, we tested the
      hypothesis that phosphate metabolism was regulated by the circadian clock network
      through the modification of food intake-associated sympathetic activation.
      Skeletal Fgf23 expression showed higher expression during the dark phase (DP)
      associated with elevated circulating FGF23 levels and enhanced phosphate
      excretion in the urine. The peaks in skeletal Fgf23 expression and urine
      epinephrine levels, a marker for sympathetic tone, shifted from DP to the light
      phase (LP) when mice were fed during LP. Interestingly, beta-adrenergic agonist,
      isoproterenol (ISO), induced skeletal Fgf23 expression when administered at ZT12,
      but this was not observed in Bmal1-deficient mice. In vitro reporter assays
      revealed that ISO trans-activated Fgf23 promoter through a cAMP responsive
      element in osteoblastic UMR-106 cells. The mechanism of circadian regulation of
      Fgf23 induction by ISO in vivo was partly explained by the suppressive effect of
      Cryptochrome1 (Cry1) on ISO signaling. These results indicate that the regulation
      of skeletal Fgf23 expression by sympathetic activity is dependent on the
      circadian clock system and may shed light on new regulatory networks of FGF23
      that could be important for understanding the physiology of phosphate metabolism.

PMID- 24302727
TI  - Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a
      role for nuclear factor-kappaB.
AB  - The aryl hydrocarbon receptor (AhR) is involved in the regulation of immune
      responses, T-cell differentiation, and immunity. Here, we show that inflammatory
      stimuli such as LPS induce the expression of AhR in human dendritic cells (DC)
      associated with an AhR-dependent increase of CYP1A1 (cytochrome P4501A1). In vivo
      data confirmed the elevated expression of AhR by LPS and the LPS-enhanced 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of CYP1A1 in thymus of B6
      mice. Inhibition of nuclear factor-kappaB (NF-kappaB) repressed both normal and
      LPS-enhanced, TCDD-inducible, AhR-dependent gene expression and canonical pathway
      control of RelA-regulated AhR-responsive gene expression. LPS-mediated induction
      of AhR was NF-kappaB-dependent, as shown in mouse embryonic fibroblasts (MEFs)
      derived from Rel null mice. AhR expression and TCDD-mediated induction of CYP1A1
      was significantly reduced in RelA-deficient MEF compared with wild type MEF cells
      and ectopic expression of RelA restored the expression of AhR and induction of
      CYP1A1 in MEF RelA null cells. Promoter analysis of the human AhR gene identified
      three putative NF-kappaB-binding elements upstream of the transcription start
      site. Mutation analysis of the AhR promoter identified one NF-kappaB site as
      responsible for mediating the induction of AhR expression by LPS and
      electrophoretic shift assays demonstrated that this NF-kappaB motif is recognized
      by the RelA/p50 heterodimer. Our results show for the first time that NF-kappaB
      RelA is a critical component regulating the expression of AhR and the induction
      of AhR-dependent gene expression in immune cells illustrating the interaction of
      AhR and NF-kappaB signaling. 

PMID- 24302728
TI  - APOLLON protein promotes early mitotic CYCLIN A degradation independent of the
      spindle assembly checkpoint.
AB  - In the mammalian cell cycle, both CYCLIN A and CYCLIN B are required for entry
      into mitosis, and their elimination is also essential to complete the process.
      During mitosis, CYCLIN A and CYCLIN B are ubiquitylated by the anaphase-promoting
      complex/cyclosome (APC/C) and then subjected to proteasomal degradation. However,
      CYCLIN A, but not CYCLIN B, begins to be degraded in the prometaphase when APC/C
      is inactivated by the spindle assembly checkpoint (SAC). Here, we show that
      APOLLON (also known as BRUCE or BIRC6) plays a role in SAC-independent
      degradation of CYCLIN A in early mitosis. APPOLON interacts with CYCLIN A that is
      not associated with cyclin-dependent kinases. APPOLON also interacts with APC/C,
      and it facilitates CYCLIN A ubiquitylation. In APPOLON-deficient cells, mitotic
      degradation of CYCLIN A is delayed, and the total, but not the cyclin-dependent
      kinase-bound, CYCLIN A level was increased. We propose APPOLON to be a novel
      regulator of mitotic CYCLIN A degradation independent of SAC. 

PMID- 24302729
TI  - Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest
      and presynaptic docking contribute to BDNF-enhanced synaptic transmission.
AB  - Appropriate mitochondrial transport and distribution are essential for neurons
      because of the high energy and Ca(2+) buffering requirements at synapses. Brain
      derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic
      transmission and plasticity. However, whether and how BDNF can regulate
      mitochondrial transport and distribution are still unclear. Here, we find that in
      cultured hippocampal neurons, application of BDNF for 15 min decreased the
      percentage of moving mitochondria in axons, a process dependent on the activation
      of the TrkB receptor and its downstream PI3K and phospholipase-Cgamma signaling
      pathways. Moreover, the BDNF-induced mitochondrial stopping requires the
      activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6)
      channels and elevated intracellular Ca(2+) levels. The Ca(2+) sensor Miro1 plays
      an important role in this process. Finally, the BDNF-induced mitochondrial
      stopping leads to the accumulation of more mitochondria at presynaptic sites.
      Mutant Miro1 lacking the ability to bind Ca(2+) prevents BDNF-induced
      mitochondrial presynaptic accumulation and synaptic transmission, suggesting that
      Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial
      presynaptic docking and neurotransmission. Together, these data suggest that
      mitochondrial transport and distribution play essential roles in BDNF-mediated
      synaptic transmission. 

PMID- 24302730
TI  - Scaffold state switching amplifies, accelerates, and insulates protein kinase C
      signaling.
AB  - Scaffold proteins localize two or more signaling enzymes in close proximity to
      their downstream effectors. A-kinase-anchoring proteins (AKAPs) are a canonical
      family of scaffold proteins known to bind protein kinase A (PKA) and other
      enzymes. Several AKAPs have been shown to accelerate, amplify, and specify signal
      transduction to dynamically regulate numerous cellular processes. However, there
      is little theory available to mechanistically explain how signaling on protein
      scaffolds differs from solution biochemistry. In our present study, we propose a
      novel kinetic mechanism for enzymatic reactions on protein scaffolds to explain
      these phenomena, wherein the enzyme-substrate-scaffold complex undergoes
      stochastic state switching to reach an active state. This model predicted
      anchored enzymatic reactions to be accelerated, amplified, and insulated from
      inhibition compared with those occurring in solution. We exploited a direct
      interaction between protein kinase C (PKC) and AKAP7alpha as a model to validate
      these predictions experimentally. Using a genetically encoded PKC activity
      reporter, we found that both the strength and speed of substrate phosphorylation
      were enhanced by AKAP7alpha. PKC tethered to AKAP7alpha was less susceptible to
      inhibition from the ATP-competitive inhibitor Go6976 and the substrate
      competitive inhibitor PKC 20-28, but not the activation-competitive inhibitor
      calphostin C. Model predictions and experimental validation demonstrated that
      insulation is a general property of scaffold tethering. Sensitivity analysis
      indicated that these findings may be applicable to many other scaffolds as well.
      Collectively, our findings provide theoretical and experimental evidence that
      scaffold proteins can amplify, accelerate, and insulate signal transduction. 

PMID- 24302731
TI  - A functional interplay between the small GTPase Rab11a and mitochondria-shaping
      proteins regulates mitochondrial positioning and polarization of the actin
      cytoskeleton downstream of Src family kinases.
AB  - It is believed that mitochondrial dynamics is coordinated with endosomal traffic
      rates during cytoskeletal remodeling, but the mechanisms involved are largely
      unknown. The adenovirus early region 4 ORF4 protein (E4orf4) subverts signaling
      by Src family kinases (SFK) to perturb cellular morphology, membrane traffic, and
      organellar dynamics and to trigger cell death. Using E4orf4 as a model, we
      uncovered a functional connection between mitochondria-shaping proteins and the
      small GTPase Rab11a, a key regulator of polarized transport via recycling
      endosomes. We found that E4orf4 induced dramatic changes in the morphology of
      mitochondria along with their mobilization at the vicinity of a polarized actin
      network typifying E4orf4 action, in a manner controlled by SFK and Rab11a.
      Mitochondrial remodeling was associated with increased proximity between Rab11a
      and mitochondrial membranes, changes in fusion-fission dynamics, and
      mitochondrial relocalization of the fission factor dynamin-related protein 1
      (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP. Knockdown of
      FIP1/RCP or inhibition of Drp1 markedly impaired mitochondrial remodeling and
      actin assembly, involving Rab11a-mediated mitochondrial dynamics in E4orf4
      induced signaling. A similar mobilization of mitochondria near actin-rich
      structures was mediated by Rab11 and Drp1 in viral Src-transformed cells and
      contributed to the biogenesis of podosome rosettes. These findings suggest a role
      for Rab11a in the trafficking of Drp1 to mitochondria upon SFK activation and
      unravel a novel functional interplay between Rab11a and mitochondria during
      reshaping of the cell cytoskeleton, which would facilitate mitochondria
      redistribution near energy-requiring actin-rich structures. 

PMID- 24302732
TI  - Structural basis of biological NO generation by octaheme oxidoreductases.
AB  - Nitric oxide is an important molecule in all domains of life with significant
      biological functions in both pro- and eukaryotes. Anaerobic ammonium-oxidizing
      (anammox) bacteria that contribute substantially to the release of fixed nitrogen
      into the atmosphere use the oxidizing power of NO to activate inert ammonium into
      hydrazine (N2H4). Here, we describe an enzyme from the anammox bacterium Kuenenia
      stuttgartiensis that uses a novel pathway to make NO from hydroxylamine. This new
      enzyme is related to octaheme hydroxylamine oxidoreductase, a key protein in
      aerobic ammonium-oxidizing bacteria. By a multiphasic approach including the
      determination of the crystal structure of the K. stuttgartiensis enzyme at 1.8 A
      resolution and refinement and reassessment of the hydroxylamine oxidoreductase
      structure from Nitrosomonas europaea, both in the presence and absence of their
      substrates, we propose a model for NO formation by the K. stuttgartiensis enzyme.
      Our results expand the understanding of the functions that the widespread family
      of octaheme proteins have. 

PMID- 24302733
TI  - Defective adipose lipolysis and altered global energy metabolism in mice with
      adipose overexpression of the lipolytic inhibitor G0/G1 switch gene 2 (G0S2).
AB  - Biochemical and cell-based studies have identified the G0S2 (G0/G1 switch gene 2)
      as a selective inhibitor of the key intracellular triacylglycerol hydrolase,
      adipose triglyceride lipase. To better understand the physiological role of G0S2,
      we constructed an adipose tissue-specific G0S2 transgenic mouse model. In
      comparison with wild type animals, the transgenic mice exhibited a significant
      increase in overall fat mass and a decrease in peripheral triglyceride
      accumulation. Basal and adrenergically stimulated lipolysis was attenuated in
      adipose explants isolated from the transgenic mice. Following fasting or
      injection of a beta3-adrenergic agonist, in vivo lipolysis and ketogenesis were
      decreased in G0S2 transgenic mice when compared with wild type animals.
      Consequently, adipose overexpression of G0S2 prevented the "switch" of energy
      substrate from carbohydrates to fatty acids during fasting. Moreover, G0S2
      overexpression promoted accumulation of more and larger lipid droplets in brown
      adipocytes without impacting either mitochondrial morphology or expression of
      oxidative genes. This phenotypic change was accompanied by defective cold
      adaptation. Furthermore, feeding with a high fat diet caused a greater gain of
      both body weight and adiposity in the transgenic mice. The transgenic mice also
      displayed a decrease in fasting plasma levels of free fatty acid, triglyceride,
      and insulin as well as improved glucose and insulin tolerance. Cumulatively,
      these results indicate that fat-specific G0S2 overexpression uncouples adiposity
      from insulin sensitivity and overall metabolic health through inhibiting adipose
      lipolysis and decreasing circulating fatty acids. 

PMID- 24302734
TI  - A glutathione-independent glyoxalase of the DJ-1 superfamily plays an important
      role in managing metabolically generated methylglyoxal in Candida albicans.
AB  - Methylglyoxal is a cytotoxic reactive carbonyl compound produced by central
      metabolism. Dedicated glyoxalases convert methylglyoxal to d-lactate using
      multiple catalytic strategies. In this study, the DJ-1 superfamily member ORF
      19.251/GLX3 from Candida albicans is shown to possess glyoxalase activity, making
      this the first demonstrated glutathione-independent glyoxalase in fungi. The
      crystal structure of Glx3p indicates that the protein is a monomer containing the
      catalytic triad Cys(136)-His(137)-Glu(168). Purified Glx3p has an in vitro
      methylglyoxalase activity (Km = 5.5 mM and kcat = 7.8 s(-1)) that is
      significantly greater than that of more distantly related members of the DJ-1
      superfamily. A close Glx3p homolog from Saccharomyces cerevisiae (YDR533C/Hsp31)
      also has glyoxalase activity, suggesting that fungal members of the Hsp31 clade
      of the DJ-1 superfamily are all probable glutathione-independent glyoxalases. A
      homozygous glx3 null mutant in C. albicans strain SC5314 displays greater
      sensitivity to millimolar levels of exogenous methylglyoxal, elevated levels of
      intracellular methylglyoxal, and carbon source-dependent growth defects,
      especially when grown on glycerol. These phenotypic defects are complemented by
      restoration of the wild-type GLX3 locus. The growth defect of Glx3-deficient
      cells in glycerol is also partially complemented by added inorganic phosphate,
      which is not observed for wild-type or glucose-grown cells. Therefore, C.
      albicans Glx3 and its fungal homologs are physiologically relevant glutathione
      independent glyoxalases that are not redundant with the previously characterized
      glutathione-dependent GLO1/GLO2 system. In addition to its role in detoxifying
      glyoxals, Glx3 and its close homologs may have other important roles in stress
      response.

PMID- 24302735
TI  - Glucose-stimulated single pancreatic islets sustain increased cytosolic ATP
      levels during initial Ca2+ influx and subsequent Ca2+ oscillations.
AB  - In pancreatic islets, insulin secretion occurs via synchronous elevation of
      Ca(2+) levels throughout the islets during high glucose conditions. This Ca(2+)
      elevation has two phases: a quick increase, observed after the glucose stimulus,
      followed by prolonged oscillations. In these processes, the elevation of
      intracellular ATP levels generated from glucose is assumed to inhibit ATP
      sensitive K(+) channels, leading to the depolarization of membranes, which in
      turn induces Ca(2+) elevation in the islets. However, little is known about the
      dynamics of intracellular ATP levels and their correlation with Ca(2+) levels in
      the islets in response to changing glucose levels. In this study, a genetically
      encoded fluorescent biosensor for ATP and a fluorescent Ca(2+) dye were employed
      to simultaneously monitor the dynamics of intracellular ATP and Ca(2+) levels,
      respectively, inside single isolated islets. We observed rapid increases in
      cytosolic and mitochondrial ATP levels after stimulation with glucose, as well as
      with methyl pyruvate or leucine/glutamine. High ATP levels were sustained as long
      as high glucose levels persisted. Inhibition of ATP production suppressed the
      initial Ca(2+) increase, suggesting that enhanced energy metabolism triggers the
      initial phase of Ca(2+) influx. On the other hand, cytosolic ATP levels did not
      fluctuate significantly with the Ca(2+) level in the subsequent oscillation
      phases. Importantly, Ca(2+) oscillations stopped immediately before ATP levels
      decreased significantly. These results might explain how food or glucose intake
      evokes insulin secretion and how the resulting decrease in plasma glucose levels
      leads to cessation of secretion. 

PMID- 24302736
TI  - cAMP-dependent protein kinase and c-Jun N-terminal kinase mediate stathmin
      phosphorylation for the maintenance of interphase microtubules during osmotic
      stress.
AB  - Dynamic microtubule changes after a cell stress challenge are required for cell
      survival and adaptation. Stathmin (STMN), a cytoplasmic microtubule-destabilizing
      phosphoprotein, regulates interphase microtubules during cell stress, but the
      signaling mechanisms involved are poorly defined. In this study ectopic
      expression of single alanine-substituted phospho-resistant mutants demonstrated
      that STMN Ser-38 and Ser-63 phosphorylation were specifically required to
      maintain interphase microtubules during hyperosmotic stress. STMN was
      phosphorylated on Ser-38 and Ser-63 in response to hyperosmolarity, heat shock,
      and arsenite treatment but rapidly dephosphorylated after oxidative stress
      treatment. Two-dimensional PAGE and Phos-tag gel analysis of stress-stimulated
      STMN phospho-isoforms revealed rapid STMN Ser-38 phosphorylation followed by
      subsequent Ser-25 and Ser-63 phosphorylation. Previously, we delineated stress
      stimulated JNK targeting of STMN. Here, we identified cAMP-dependent protein
      kinase (PKA) signaling as responsible for stress-induced STMN Ser-63
      phosphorylation. Increased cAMP levels induced by cholera toxin triggered potent
      STMN Ser-63 phosphorylation. Osmotic stress stimulated an increase in PKA
      activity and elevated STMN Ser-63 and CREB (cAMP-response element-binding
      protein) Ser-133 phosphorylation that was substantially attenuated by
      pretreatment with H-89, a PKA inhibitor. Interestingly, PKA activity and
      subsequent phosphorylation of STMN were augmented in the absence of JNK
      activation, indicating JNK and PKA pathway cross-talk during stress regulation of
      STMN. Taken together our study indicates that JNK- and PKA-mediated STMN Ser-38
      and Ser-63 phosphorylation are required to preserve interphase microtubules in
      response to hyperosmotic stress. 

PMID- 24302737
TI  - Non-invasive in-cell determination of free cytosolic [NAD+]/[NADH] ratios using
      hyperpolarized glucose show large variations in metabolic phenotypes.
AB  - Accumulating evidence suggest that the pyridine nucleotide NAD has far wider
      biological functions than its classical role in energy metabolism. NAD is used by
      hundreds of enzymes that catalyze substrate oxidation and, as such, it plays a
      key role in various biological processes such as aging, cell death, and oxidative
      stress. It has been suggested that changes in the ratio of free cytosolic
      [NAD(+)]/[NADH] reflects metabolic alterations leading to, or correlating with,
      pathological states. We have designed an isotopically labeled metabolic bioprobe
      of free cytosolic [NAD(+)]/[NADH] by combining a magnetic enhancement technique
      (hyperpolarization) with cellular glycolytic activity. The bioprobe reports free
      cytosolic [NAD(+)]/[NADH] ratios based on dynamically measured in-cell
      [pyruvate]/[lactate] ratios. We demonstrate its utility in breast and prostate
      cancer cells. The free cytosolic [NAD(+)]/[NADH] ratio determined in prostate
      cancer cells was 4 times higher than in breast cancer cells. This higher ratio
      reflects a distinct metabolic phenotype of prostate cancer cells consistent with
      previously reported alterations in the energy metabolism of these cells. As a
      reporter on free cytosolic [NAD(+)]/[NADH] ratio, the bioprobe will enable better
      understanding of the origin of diverse pathological states of the cell as well as
      monitor cellular consequences of diseases and/or treatments. 

PMID- 24302738
TI  - Ribosomal protein S6, a target of rapamycin, is involved in the regulation of
      rRNA genes by possible epigenetic changes in Arabidopsis.
AB  - The target of rapamycin (TOR) kinase pathway regulates various biological
      processes, including translation, synthesis of ribosomal proteins, and
      transcription of rRNA. The ribosomal protein S6 (RPS6) is one of the well known
      downstream components of the TOR pathway. Ribosomal proteins have been known to
      have diverse functions in regulating cellular metabolism as well as protein
      synthesis. So far, however, little is known about other possible role(s) of RPS6
      in plants, besides being a component of the 40 S ribosomal subunit and acting as
      a target of TOR. Here, we report that RPS6 may have a novel function via
      interaction with histone deacetylase 2B (AtHD2B) that belongs to the plant
      specific histone deacetylase HD2 family. RPS6 and AtHD2B were localized to the
      nucleolus. Co-expression of RPS6 and AtHD2B caused a change in the location of
      both RPS6 and AtHD2B to one or several nucleolar spots. ChIP analysis suggests
      that RPS6 directly interacts with the rRNA gene promoter. Protoplasts
      overexpressing both AtHD2B and RPS6 exhibited down-regulation of pre-18 S rRNA
      synthesis with a concomitant decrease in transcription of some of the ribosomal
      proteins, suggesting their direct role in ribosome biogenesis and plant
      development. This is consistent with the mutation in rps6b that results in
      reduction in 18 S rRNA transcription and decreased root growth. We propose that
      the interaction between RPS6 and AtHD2B brings about a change in the chromatin
      structure of rDNA and thus plays an important role in linking TOR signaling to
      rDNA transcription and ribosome biogenesis in plants. 

PMID- 24302739
TI  - Three different classes of aminotransferases evolved prephenate aminotransferase
      functionality in arogenate-competent microorganisms.
AB  - The aromatic amino acids phenylalanine and tyrosine represent essential sources
      of high value natural aromatic compounds for human health and industry. Depending
      on the organism, alternative routes exist for their synthesis. Phenylalanine and
      tyrosine are synthesized either via phenylpyruvate/4-hydroxyphenylpyruvate or via
      arogenate. In arogenate-competent microorganisms, an aminotransferase is required
      for the transamination of prephenate into arogenate, but the identity of the
      genes is still unknown. We present here the first identification of prephenate
      aminotransferases (PATs) in seven arogenate-competent microorganisms and the
      discovery that PAT activity is provided by three different classes of
      aminotransferase, which belong to two different fold types of pyridoxal phosphate
      enzymes: an aspartate aminotransferase subgroup 1beta in tested alpha- and beta
      proteobacteria, a branched-chain aminotransferase in tested cyanobacteria, and an
      N-succinyldiaminopimelate aminotransferase in tested actinobacteria and in the
      beta-proteobacterium Nitrosomonas europaea. Recombinant PAT enzymes exhibit high
      activity toward prephenate, indicating that the corresponding genes encode bona
      fide PAT. PAT functionality was acquired without other modification of substrate
      specificity and is not a general catalytic property of the three classes of
      aminotransferases. 

PMID- 24302740
TI  - AccR is a master regulator involved in carbon catabolite repression of the
      anaerobic catabolism of aromatic compounds in Azoarcus sp. CIB.
AB  - Here we characterized the first known transcriptional regulator that accounts for
      carbon catabolite repression (CCR) control of the anaerobic catabolism of
      aromatic compounds in bacteria. The AccR response regulator of Azoarcus sp. CIB
      controls succinate-responsive CCR of the central pathways for the anaerobic
      catabolism of aromatics by this strain. Phosphorylation of AccR to AccR-P
      triggers a monomer-to-dimer transition as well as the ability to bind to the
      target promoter and causes repression both in vivo and in vitro. Substitution of
      the Asp(60) phosphorylation target residue of the N-terminal receiver motif of
      AccR to a phosphomimic Glu residue generates a constitutively active derivative
      that behaves as a superrepressor of the target genes. AccR-P binds in vitro to a
      conserved inverted repeat (ATGCA-N6-TGCAT) present at two different locations
      within the PN promoter of the bzd genes for anaerobic benzoate degradation.
      Because the DNA binding-proficient C-terminal domain of AccR is monomeric, we
      propose an activation mechanism in which phosphorylation of Asp(60) of AccR
      alleviates interdomain repression mediated by the N-terminal domain. The presence
      of AccR-like proteins encoded in the genomes of other beta-proteobacteria of the
      Azoarcus/Thauera group further suggests that AccR constitutes a master regulator
      that controls anaerobic CCR in these bacteria. 

PMID- 24302741
TI  - Leptin signaling is required for leucine deprivation-enhanced energy expenditure.
AB  - Leptin signaling in the hypothalamus is crucial in energy homeostasis. We have
      previously shown that dietary deprivation of the essential amino acid leucine in
      mice stimulates fat loss by increasing energy expenditure. The involvement of
      leptin signaling in this regulation, however, has not been reported. Here, we
      show that leucine deprivation promotes leptin signaling in mice maintained on an
      otherwise normal diet and restores leptin responses in mice maintained on a high
      fat diet, a regimen known to induce leptin resistance. In addition, we found that
      leucine deprivation stimulated energy expenditure, and fat loss was largely
      blocked in db/db mice homozygous for a mutation in leptin receptor and a knock-in
      mouse line Y3F with abrogation of leptin receptor Tyr(1138)-mediated signal
      transducer and activator transcript 3 signaling. Overall, our studies describe a
      novel link between hypothalamic leptin signaling and stimulation of energy
      expenditure under leucine deprivation. 

PMID- 24302743
TI  - SMG-ly knocking out gene expression in specific cells: an educational primer for
      use with "a novel strategy for cell-autonomous gene knockdown in caenorhabditis
      elegans defines a cell-specific function for the G-protein subunit GOA-1".
AB  - A recent article by Maher et al. in GENETICS introduces an alternative approach
      to cell-type-specific gene knockdown in Caenorhabditis elegans, using nonsense
      mediated decay. This strategy has the potential to be applicable to other
      organisms (this strategy requires that animals can survive without nonsense
      mediated decay-not all can). This Primer article provides a guide and resource
      for educators and students by describing different gene knockdown methodologies,
      by assisting with the technically difficult portions of the Maher et al. article,
      and by providing conceptual questions relating to the article.

PMID- 24302742
TI  - Thermodynamic analysis of the binding of 2F5 (Fab and immunoglobulin G forms) to
      its gp41 epitope reveals a strong influence of the immunoglobulin Fc region on
      affinity.
AB  - Immunotherapies and vaccines based on the induction of broadly neutralizing
      monoclonal antibodies (bNAbs) have become outstanding strategies against HIV-1.
      Diverse bNAbs recognizing different regions of the HIV-1 envelope have been
      identified and extensively studied. However, there is little information about
      the thermodynamics of binding of these bNAbs and their epitopes. We used
      isothermal titration calorimetry to characterize thermodynamically the
      interactions between bNAb2F5 (in both the IgG and Fab forms) and its functional
      and core epitope peptides. We found that these interactions are enthalpically
      driven and opposed by a negative entropy change. The highest affinity was found
      for 2F5 IgG for its functional epitope, indicating that additional interactions
      involving residues flanking the core epitope contribute strongly to higher
      affinity. In addition, the strong influence of the Fc region on the binding
      affinity suggests long-range allosteric effects within IgG. Our results provide
      useful information for developing new therapeutics against HIV-1 and, in a
      broader scope, contribute to a better understanding of antigen-antibody
      recognition.

PMID- 24302746
TI  - Serum Dickkopf 1 levels in sclerostin deficiency.
AB  - CONTEXT: Sclerostin and Dickkopf 1 (DKK1) are antagonists of the canonical Wnt
      signaling pathway, both binding to the same low-density lipoprotein receptor
      related protein 5/6 on osteoblasts, thereby inhibiting bone formation. It is not
      known whether there is an interaction between sclerostin and DKK1. OBJECTIVE: We
      examined whether a lack of sclerostin is compensated by increased DKK1 levels.
      DESIGN, SETTING, AND PATIENTS: We measured DKK1 levels in serum samples of
      patients and carriers of sclerosteosis (19 patients, 24 carriers) and van Buchem
      disease (VBD) (13 patients, 22 carriers) and 25 healthy controls. Sclerosteosis
      and VBD are caused by deficient sclerostin synthesis and are characterized by
      increased bone formation and hyperostotic phenotypes. MAIN OUTCOME MEASURES: DKK1
      levels were compared between patients and carriers, and between patients and
      healthy controls. We also examined associations between levels of DKK1 and the
      bone turnover markers procollagen type 1 amino-terminal propeptide and carboxy
      terminal cross-linking telopeptide. RESULTS: We found that DKK1 levels were
      significantly higher in patients with both sclerosteosis (4.28 ng/mL [95%
      confidence interval (CI), 3.46-5.11 ng/mL]) and VBD (5.28 ng/mL [95% CI, 3.84
      6.71 ng/mL]), compared to levels in carriers of the two diseases (sclerosteosis,
      2.03 ng/mL [95% CI, 1.78-2.29 ng/mL], P < .001; VBD, 3.47 ng/mL [95% CI, 2.97
      3.97 ng/mL], P = 0.017) and to levels in healthy controls (2.77 ng/mL [95% CI,
      2.45-3.08 ng/mL]; P = 0.004 and P < .001, respectively). Serum DKK1 levels were
      positively associated with levels of procollagen type 1 amino-terminal propeptide
      and carboxy-terminal cross-linking telopeptide in both disorders. CONCLUSIONS:
      These results suggest that increased DKK1 levels observed in patients with
      sclerosteosis and VBD represent an adaptive response to the increased bone
      formation characterizing these diseases, although these increased levels do not
      compensate for the lack of sclerostin on bone formation.

PMID- 24302747
TI  - A possible new mechanism in the pathophysiology of polycystic ovary syndrome
      (PCOS): the discovery that leukocyte telomere length is strongly associated with
      PCOS.
AB  - CONTEXT: Telomeres are specialized chromatin structures located at the ends of
      eukaryotic chromosomes, and telomere length plays a clear role in various
      diseases. However, it is not known whether telomere length is related to
      polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized that leukocyte
      telomere length (LTL) plays an important role in the pathophysiology of PCOS.
      DESIGN: We used an established and validated quantitative PCR technique to
      measure the mean LTL in a large sample of PCOS patients and controls. We used
      logistic regression and multiple linear regression to analyze the association of
      PCOS and several related clinical parameters with the age-adjusted ratio of the
      telomere repeat length to the copy number of a single-copy gene (T/S). RESULTS:
      Individuals with PCOS (n = 698) exhibited significantly shorter LTLs than the
      controls (n = 611) after adjusting for age (0.764 +/- 0.016 vs 0.876 +/- 0.023; P
      = .001; odds ratio = 1.403; 95% confidence interval, 1.150-1.712). The mean
      telomere length in the leukocytes of PCOS patients was comparable to that of
      control individuals who were on average 6.16 years older. Individuals having
      shorter telomere lengths (middle and lowest tertile) had significantly higher
      disease risk than those having the longest telomere length (highest tertile)
      (odds ratio = 1.614; 95% confidence interval, 1.262-2.066; P = .0001) after
      adjusting for age. In addition, a significant correlation between the LTL and the
      level of dehydroepiandrosterone sulfate was observed in controls (r = -0.185; P =
      .01). CONCLUSION: We provide the first report that LTL is strongly associated
      with PCOS. This study suggests a new role for LTL in the pathophysiology of PCOS
      and might have important implications for our understanding of the etiology of
      the disease.

PMID- 24302748
TI  - Chronic starvation secondary to anorexia nervosa is associated with an adaptive
      suppression of resting energy expenditure.
AB  - BACKGROUND: Chronic starvation is accompanied by a reduction in resting energy
      expenditure (REE). It is not clear whether this is due mainly to a reduction in
      body mass or also involves a significant reduction in the cellular metabolic rate
      of the fat-free mass (FFM). OBJECTIVES: The main goal was to compare measured REE
      (REEm) with REE predicted by dual-energy X-ray absorptiometry modeling of organ
      tissue mass (REEp) in malnourished patients with severe anorexia nervosa (AN) and
      in healthy lean control subjects. REE adjusted for FFM and fat mass was also
      compared between the groups. DESIGN: This was a cross-sectional study of 30
      patients with AN and 25 lean control subjects. REE was measured by indirect
      calorimetry. Body composition was modeled using dual-energy X-ray absorptiometry,
      and REE was predicted for each group based on organ-tissue mass. RESULTS: REEm
      was significantly lower than REEp in subjects with AN (854 +/- 41 vs 1080 +/- 25
      kcal/d, P < .001), but not in control subjects. In addition, REE adjusted for
      both FFM and fat mass was significantly lower in the subjects with AN (1031 +/-
      37 vs 1178 +/- 32 kcal/d, P < .01). Finally, compared with the lean control
      subjects, both organ and skeletal muscle mass were approximately 20% smaller in
      subjects with AN. CONCLUSIONS: Chronic starvation is accompanied by a significant
      reduction in the metabolic rate of the FFM. The organs and/or tissues accounting
      for this are unknown. In addition, this study suggests that protein is mobilized
      proportionately from organs and skeletal muscle during starvation. This too may
      be an adaptive response to chronic starvation.

PMID- 24302749
TI  - Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to
      21-hydroxylase deficiency.
AB  - CONTEXT: Reports on psychiatric morbidity in males with congenital adrenal
      hyperplasia (CAH) are lacking. OBJECTIVE: The aim was to study psychiatric
      disorders in CAH males. DESIGN, SETTING, AND PARTICIPANTS: We studied males with
      CAH (21-hydroxylase deficiency, n = 253; CYP21A2 mutations known, n = 185), and
      compared them with controls (n = 25 300). Data were derived through linkage of
      national population-based registers. We assessed the subgroups of CYP21A2
      genotype separately (null, I2splice, I172N, P30L, and NC), as well as outcomes
      before and after the introduction of national neonatal screening in 1986. MAIN
      OUTCOME MEASURES: Psychiatric disorders including attempted and completed suicide
      (suicidality) were reviewed. RESULTS: Psychiatric disorders (suicidality not
      included), suicidality, and alcohol misuse were increased in CAH males compared
      with controls (odds ratios, 1.5, 2.3, and 1.9; 95% confidence intervals, 1.1-2.2,
      1.1-5.0, and 1.0-3.5, respectively). In the null genotype group, no increased
      rates were seen; in the I2splice group, psychiatric disorders, personality
      disorders, and alcohol misuse were increased; in the I172N group, suicide attempt
      and drug misuse were increased; and in the P30L and NC groups, psychotic
      disorders were increased. In CAH males born before the neonatal screening, the
      rates of psychiatric disorders and suicidality were increased, but only psychotic
      disorders increased in those born afterward. There was no increased risk for any
      neurodevelopmental disorder. CONCLUSIONS: CAH males have an increased psychiatric
      morbidity. Psychiatric morbidity was not raised in the most severe genotype
      group. Late diagnosis of CAH may explain some of the findings. Those born before
      the introduction of neonatal screening were more affected, which may be explained
      by the higher age.

PMID- 24302750
TI  - Adjuvant therapies and patient and tumor characteristics associated with survival
      of adult patients with adrenocortical carcinoma.
AB  - CONTEXT: Adrenocortical carcinoma is a rare malignant endocrine neoplasia.
      Studies regarding outcome and prognostic factors rely on fairly small studies.
      Here we summarize the experience with patients with a diagnosis of adrenocortical
      carcinoma from a large tertiary referral center. OBJECTIVE: The objective of the
      study was to identify prognostic factors in patients with adrenocortical
      carcinoma and evaluate adjuvant treatment strategies. DESIGN: Patient data were
      collected in a retrospective single-center study. Epidemiological, patient, and
      tumor characteristics were analyzed for prognostic factors regarding overall and
      recurrence-free survival in Cox regression models (multivariable and
      univariable). RESULTS: Three hundred ninety-one adult patients with the diagnosis
      of adrenocortical carcinoma were identified. Median overall survival was 35.2
      months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR
      stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were
      identified as negative prognostic factors (HR for death, HR for recurrence).
      Mitotane therapy increases recurrence-free survival, an effect that was
      significantly further improved by adjuvant radiation therapy but did not impact
      overall survival. Patients with open adrenalectomy had improved overall survival.
      CONCLUSIONS: This study increases the evidence for adverse risk factors (cortisol
      production, high tumor stage, and high tumor grade) and suggests the following
      therapy approach: adrenocortical carcinoma patients should be treated with open
      adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction
      with radiation, should be considered to delay tumor recurrence.

PMID- 24302751
TI  - Novel associations in disorders of sex development: findings from the I-DSD
      Registry.
AB  - CONTEXT: The focus of care in disorders of sex development (DSD) is often
      directed to issues related to sex and gender development. In addition, the
      molecular etiology remains unclear in the majority of cases. OBJECTIVE: To report
      the range of associated conditions identified in the international DSD (I-DSD)
      Registry. DESIGN, SETTING, AND PATIENTS: Anonymized data were extracted from the
      I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations,
      and associated anomalies. If necessary, clarification was sought from the
      reporting clinician. RESULTS: Of 649 accessible cases, associated conditions
      occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two
      conditions, 20 (12%) had three conditions, and 14 (8%) had four or more
      conditions. Karyotypes with most frequently reported associations included 45,X
      with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY
      with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112
      cases of 46,XY DSD, the commonest conditions included small for gestational age
      in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders
      in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies
      were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected
      androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these
      had confirmed androgen receptor mutations. CONCLUSIONS: Over a quarter of the
      cases in the I-DSD Registry have an additional condition. These associations can
      direct investigators toward novel genetic etiology and also highlight the need
      for more holistic care of the affected person.

PMID- 24302752
TI  - Detection of thyroid cancer stem cells in papillary thyroid carcinoma.
AB  - CONTEXT: Special populations of cells that can efficiently initiate tumor growth
      have been characterized, and this feature supports the cancer stem cell theory.
      These cancer stem cell populations have been identified with CD44 and POU5F1.
      Most cancer stem cells express high levels of CD44 and low levels of CD24. In
      thyroid lesions, cancer stem cells have been detected in anaplastic carcinoma.
      However, little is known about the presence of cancer stem cells in papillary
      thyroid carcinoma (PTC), especially in recurrent PTC. OBJECTIVE AND DESIGN: PTC
      cells were labeled and sorted by flow cytometry to obtain two populations. Total
      RNA was prepared from cells with high CD44 and CD24 expressions (CD44+CD24+) and
      from cells with high CD44 and low CD24 expressions (CD44+CD24-). The expressions
      of the stem cell marker POU5F1 and several differentiated thyroid markers were
      measured via real-time PCR. RESULTS: CD44+CD24- cells were present in all PTCs
      tested, and the percentage of these cells was higher in clinically aggressive
      recurrent PTC than in less aggressive primary PTCs. Higher expression of POU5F1
      was found in CD44+CD24- cells compared with that of CD44+CD24+ cells. The
      expression of POU5F1 was higher in thyrospheroids grown in serum-free condition
      than in cells grown in the presence of serum from the same patient, and the tumor
      was initiated in mice using thyrospheroids. CONCLUSIONS: The percentage of
      CD44+CD24- cells varied from tumor to tumor. Our findings suggest that cancer
      stem cells are present in PTC.

PMID- 24302753
TI  - Changes in household, transport and recreational physical activity and television
      viewing time across the transition to retirement: longitudinal evidence from the
      EPIC-Norfolk cohort.
AB  - BACKGROUND: Retirement is associated with an increase in recreational physical
      activity but its impact on other domains of activity (at home, for transport) and
      sedentary behaviour, such as time spent watching television (TV) is unknown. We
      examined the association between retirement and changes in domain-specific and
      overall activity and TV viewing. METHODS: Data were derived from the population
      based EPIC (European Prospective Investigation into Cancer)-Norfolk cohort.
      Physical activity and TV viewing time were self-reported at baseline (1997-2000)
      and follow-up 2 (2006-2007) by 3334 participants employed at baseline, of whom
      785 (24%) were retired at follow-up 1 (2002-2006). Multivariable regression
      models were fitted to estimate the association between retirement and changes in
      physical activity and weekly TV viewing time. RESULTS: Compared with continued
      employment, retirement was associated with a decline in overall activity (men:
      non-manual, -40.9 MET h/wk; manual, -49.6 MET h/wk; women: non-manual, -26.9 MET
      h/wk; manual, -31.6 MET h/wk; all p<0.001 (MET, metabolic equivalent of task)).
      Domain-specific activity declined for transport and occupational (p<0.001) and
      increased for recreational (p<0.02) and household (p<=0.002) activity. We
      observed significant interaction between retirement and social class in respect
      of overall and domain-specific activity apart from household activity. Retirement
      was associated with a mean increase in TV viewing time, with the largest increase
      among manual social classes (men: +3.9 h/wk; women: +2.8 h/wk; both p<0.001).
      CONCLUSIONS: Interventions should aim to promote household and transport as well
      as recreational activity. Further research on the impact of retirement on
      sedentary behaviour is needed.

PMID- 24302755
TI  - The effect of chronic cytomegalovirus infection on pneumococcal vaccine
      responses.
AB  - BACKGROUND: Immune function declines with age and has been associated with
      reduced vaccine responsiveness. Chronic infection with cytomegalovirus (CMV) has
      been proposed as a contributor to poorer responses in older adults. A
      pneumococcal vaccine has been recommended in the United Kingdom for those aged
      >65 years since 2003 to prevent pneumococcal disease. METHODS: We evaluated the
      effect of age and CMV status on pneumococcal vaccine responses in 348 individuals
      aged 50-70 years. RESULTS: We found participant age to be associated with
      serotype-specific and functional antibody titers after pneumococcal vaccination,
      with a mean 6.2% (95% confidence interval, 2.9%-9.5%) reduction in
      postvaccination functional antibody titers per year. CMV status was not
      associated with serotype-specific immunoglobulin G concentrations or functional
      antibody titers after pneumococcal vaccination. However, CMV seropositivity was
      associated with higher levels of prevaccination functional antibody for 4 of 7
      pneumococcal serotypes assessed. CONCLUSIONS: These data imply that CMV infection
      is not directly responsible for the decline in pneumococcal vaccine responses
      seen with age but suggest that CMV-seropositive individuals differ in their
      natural exposure to pneumococci or have altered mucosal immune responses after
      colonization with this organism.

PMID- 24302756
TI  - HIV migration between blood and cerebrospinal fluid or semen over time.
AB  - Previous studies reported associations between neuropathogenesis and human
      immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF)
      and between sexual transmission and human immunodeficiency virus type 1 (HIV)
      compartmentalization in semen. It remains unclear, however, how
      compartmentalization dynamics change over time. To address this, we used
      statistical methods and Bayesian phylogenetic approaches to reconstruct temporal
      dynamics of HIV migration between blood and CSF and between blood and the male
      genital tract. We investigated 11 HIV-infected individuals with paired semen and
      blood samples and 4 individuals with paired CSF and blood samples. Aligned
      partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using
      a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral
      compartmentalization, using tree-based and distance-based methods; and (3)
      analysis of migration events, using a discrete Bayesian asymmetric
      phylogeographic approach of diffusion with Markov jump counts estimation.
      Finally, we evaluated potential correlates of viral gene flow across anatomical
      compartments. We observed bidirectional replenishment of viral compartments and
      asynchronous peaks of viral migration from and to blood over time, suggesting
      that disruption of viral compartment is transient and directionally selected.
      These findings imply that viral subpopulations in anatomical sites are an active
      part of the whole viral population and that compartmental reservoirs could have
      implications in future eradication studies. 

PMID- 24302754
TI  - Role of chromatin in water stress responses in plants.
AB  - As sessile organisms, plants are exposed to environmental stresses throughout
      their life. They have developed survival strategies such as developmental and
      morphological adaptations, as well as physiological responses, to protect
      themselves from adverse environments. In addition, stress sensing triggers large
      scale transcriptional reprogramming directed at minimizing the deleterious effect
      of water stress on plant cells. Here, we review recent findings that reveal a
      role of chromatin in water stress responses. In addition, we discuss data in
      support of the idea that chromatin remodelling and modifying enzymes may be
      direct targets of stress signalling pathways. Modulation of chromatin regulator
      activity by these signaling pathways may be critical in minimizing potential
      trade-offs between growth and stress responses. Alterations in the chromatin
      organization and/or in the activity of chromatin remodelling and modifying
      enzymes may furthermore contribute to stress memory. Mechanistic insight into
      these phenomena derived from studies in model plant systems should allow future
      engineering of broadly drought-tolerant crop plants that do not incur unnecessary
      losses in yield or growth. 

PMID- 24302758
TI  - Incidence, risk factors and treatment outcomes of extravasation of cytotoxic
      agents in an outpatient chemotherapy clinic.
AB  - OBJECTIVE: Extravasation, the accidental leakage of an anticancer agent from a
      vessel into the surrounding tissues, can lead to irreversible local injuries and
      severe disability. Despite its considerable clinical importance, evidence-based
      information on extravasation in chemotherapy is lacking. This study characterized
      the clinical features of extravasation and identified issues to be resolved in
      current cancer chemotherapy performed in outpatient settings. METHODS: We
      retrospectively reviewed the medical charts of patients who received chemotherapy
      and sustained extravasation in our Outpatient Chemotherapy Clinic from April 2007
      to August 2012. Chemotherapy administration and extravasation management
      procedures were standardized using the in-house chemotherapy guideline. RESULTS:
      Among 43 557 patients who received chemotherapy, 35 (0.08%) experienced
      extravasation. The duration between the start of infusion and extravasation was
      >2 h in 28 (80.0%) patients. The severity of extravasation was Grades 1, 2 and 3
      in 28, 2 and 5 patients, respectively-three of whom were associated with port
      trouble. The contributing factor for extravasation was walking in 11 (31.4%)
      patients. All extravasations were cured without surgical intervention by
      management according to our guidelines. CONCLUSIONS: The incidence of
      extravasation is as low as 0.08%, using our in-house chemotherapy guideline.
      Extravasation from implanted ports tends to be severe.

PMID- 24302757
TI  - Natural cytotoxicity receptor-dependent natural killer cytolytic activity
      directed at hepatitis C Virus (HCV) is associated with liver inflammation,
      African American race, IL28B genotype, and response to pegylated
      interferon/ribavirin therapy in chronic HCV infection.
AB  - BACKGROUND: Natural killer (NK) cells are implicated in the pathogenesis of
      hepatitis C virus (HCV) infection and outcome of interferon (IFN)-alpha based
      therapy, although mechanisms remain unclear. METHODS: To evaluate NK ability to
      control HCV infection, we analyzed healthy donor and HCV-infected donor NK-cell
      cytolytic activity directed at HCV-infected target cells. RESULTS: HCV-infected
      subjects' natural cytotoxicity receptor (NCR)-dependent NK-cell cytolytic
      activity directed at HCV-infected and uninfected Huh7.5 target cells was greater
      than that of cells from healthy donors, and this localized to the African
      American subset. However, IFN-alpha-enhanced NK cytolytic function was lower in
      HCV-infected subjects, again localized mainly to the African American subset.
      Additionally, whereas HCV-infected Huh7.5 cells were more readily targeted than
      uninfected cells, the selectivity of cytolytic activity for infected targets was
      lower during HCV infection and after IFN-alpha stimulation, and lower selectivity
      was in part attributable to greater NKp46 expression. Furthermore, cytolytic
      activity was associated with higher serum aspartate aminotransferase, rs12979860
      IL28B genotype, and in vivo response to pegylated IFN/ribavirin therapy.
      CONCLUSIONS: These data indicate that during chronic HCV infection, race
      associated increase in NCR expression and IL28B-associated cytolytic activity may
      participate in host response to IFN-alpha-containing HCV therapy.

PMID- 24302759
TI  - Prospective phase II study of image-guided local boost using a real-time tumor
      tracking radiotherapy (RTRT) system for locally advanced bladder cancer.
AB  - OBJECTIVE: The real-time tumor-tracking radiotherapy system with fiducial markers
      has the advantage that it can be used to verify the localization of the markers
      during radiation delivery in real-time. We conducted a prospective Phase II study
      of image-guided local-boost radiotherapy for locally advanced bladder cancer
      using a real-time tumor-tracking radiotherapy system for positioning, and here we
      report the results regarding the safety and efficacy of the technique. METHODS:
      Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were
      clinically inoperable or refused surgery were enrolled. Transurethral tumor
      resection and 40 Gy irradiation to the whole bladder was followed by the
      transurethral endoscopic implantation of gold markers in the bladder wall around
      the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor
      while maintaining the displacement from the planned position at less than +/-2 mm
      during radiation delivery using a real-time tumor-tracking radiotherapy system.
      The toxicity, local control and survival were evaluated. RESULTS: Among the 20
      patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up
      period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each
      observed in one patient. The local-control rate, overall survival and cause
      specific survival with the native bladder after 5 years were 64, 61 and 65%.
      CONCLUSIONS: Image-guided local-boost radiotherapy using a real-time tumor
      tracking radiotherapy system can be safely accomplished, and the clinical outcome
      is encouraging. A larger prospective multi-institutional study is warranted for
      more precise evaluations of the technological efficacy and patients' quality of
      life.

PMID- 24302760
TI  - Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of
      heme oxygenase-1.
AB  - Accumulation of foam cells in the neointima represents a key event in
      atherosclerosis. We previously demonstrated that Tanshinone IIA (Tan), a
      lipophilic bioactive compound extracted from Salvia miltiorrhiza Bunge, inhibits
      experimental atherogenesis, yet the detailed mechanisms are not fully understood.
      In this study, we sought to explore the potential effects of Tan on lipid
      accumulation in macrophage foam cells and the underlying molecular mechanisms.
      Our data indicate that Tan treatment reduced the content of macrophages,
      cholesterol accumulation, and the development of atherosclerotic plaque in
      apolipoprotein E-deficient mice. In human macrophages, Tan ameliorated oxidized
      low density lipoporotein (oxLDL)-elicited foam cell formation by inhibiting oxLDL
      uptake and promoting cholesterol efflux. Mechanistically, Tan markedly reduced
      the expression of scavenger receptor class A and increased the expression of ATP
      binding cassette transporter A1 (ABCA1) and ABCG1 in lipid-laden macrophages via
      activation of the extracellular signal-regulated kinase (ERK)/nuclear factor
      erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Tan
      treatment induced the phosphorylation and nuclear translocation of Nrf2 and
      subsequently increased the expression of HO-1, and these effects were abolished
      by the specific ERK inhibitors, PD98059 and U0126. Moreover, HO-1 small
      interfering RNA or zinc protoporphyrin (a HO-1 inhibitor) abrogated Tan-mediated
      suppression of lipid accumulation in macrophages. Our current findings
      demonstrate that a novel HO-1-dependent mechanism is involved in the regulation
      of cholesterol balance by Tan. 

PMID- 24302762
TI  - Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains
      of rabphilin 3A and synaptotagmin 1.
AB  - Proteins containing C2 domains are the sensors for Ca(2+) and PI(4,5)P2 in a
      myriad of secretory pathways. Here, the use of a free-mounting system has enabled
      us to capture an intermediate state of Ca(2+) binding to the C2A domain of
      rabphilin 3A that suggests a different mechanism of ion interaction. We have also
      determined the structure of this domain in complex with PI(4,5)P2 and IP3 at
      resolutions of 1.75 and 1.9 A, respectively, unveiling that the polybasic cluster
      formed by strands beta3-beta4 is involved in the interaction with the
      phosphoinositides. A comparative study demonstrates that the C2A domain is highly
      specific for PI(4,5)P2/PI(3,4,5)P3, whereas the C2B domain cannot discriminate
      among any of the diphosphorylated forms. Structural comparisons between C2A
      domains of rabphilin 3A and synaptotagmin 1 indicated the presence of a key
      glutamic residue in the polybasic cluster of synaptotagmin 1 that abolishes the
      interaction with PI(4,5)P2. Together, these results provide a structural
      explanation for the ability of different C2 domains to pull plasma and vesicle
      membranes close together in a Ca(2+)-dependent manner and reveal how this family
      of proteins can use subtle structural changes to modulate their sensitivity and
      specificity to various cellular signals. 

PMID- 24302763
TI  - PirB regulates a structural substrate for cortical plasticity.
AB  - Experience-driven circuit changes underlie learning and memory. Monocular
      deprivation (MD) engages synaptic mechanisms of ocular dominance (OD) plasticity
      and generates robust increases in dendritic spine density on L5 pyramidal
      neurons. Here we show that the paired immunoglobulin-like receptor B (PirB)
      negatively regulates spine density, as well as the threshold for adult OD
      plasticity. In PirB(-/-) mice, spine density and stability are significantly
      greater than WT, associated with higher-frequency miniature synaptic currents,
      larger long-term potentiation, and deficient long-term depression. Although MD
      generates the expected increase in spine density in WT, in PirB(-/-) this
      increase is occluded. In adult PirB(-/-), OD plasticity is larger and more rapid
      than in WT, consistent with the maintenance of elevated spine density. Thus, PirB
      normally regulates spine and excitatory synapse density and consequently the
      threshold for new learning throughout life. 

PMID- 24302764
TI  - KpsC and KpsS are retaining 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)
      transferases involved in synthesis of bacterial capsules.
AB  - Capsular polysaccharides (CPSs) are high-molecular-mass cell-surface
      polysaccharides, that act as important virulence factors for many pathogenic
      bacteria. Several clinically important Gram-negative pathogens share similar
      systems for CPS biosynthesis and export; examples include Escherichia coli,
      Campylobacter jejuni, Haemophilus influenzae, Neisseria meningitidis, and
      Pasteurella multocida. Each CPS contains a serotype-specific repeat-unit
      structure, but the glycans all possess a lipid moiety at their reducing termini.
      In E. coli and N. meningitidis, the predominant lipid is a
      lysophosphatidylglycerol moiety that is attached to the repeat-unit domain of the
      CPS via multiple residues of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo), referred
      to as a poly-Kdo linker. The Kdo residues are beta-linked, suggesting that they
      are synthesized by retaining glycosyltransferases. To date, the only
      characterized Kdo transferases are the inverting enzymes that catalyze the alpha
      linkages found in lipopolysaccharide. Here, we identify two conserved proteins
      from CPS assembly systems, KpsC and KpsS, as the beta-Kdo-transferases and
      demonstrate in vitro reconstitution of poly-Kdo linker assembly on a fluorescent
      phosphatidylglycerol acceptor. KpsS adds the first Kdo residue, and this reaction
      product is then extended by KpsC. Cross-complementation experiments demonstrate
      that the E. coli and N. meningitidis protein homologs are functionally conserved.

PMID- 24302765
TI  - Dysferlin stabilizes stress-induced Ca2+ signaling in the transverse tubule
      membrane.
AB  - Dysferlinopathies, most commonly limb girdle muscular dystrophy 2B and Miyoshi
      myopathy, are degenerative myopathies caused by mutations in the DYSF gene
      encoding the protein dysferlin. Studies of dysferlin have focused on its role in
      the repair of the sarcolemma of skeletal muscle, but dysferlin's association with
      calcium (Ca(2+)) signaling proteins in the transverse (t-) tubules suggests
      additional roles. Here, we reveal that dysferlin is enriched in the t-tubule
      membrane of mature skeletal muscle fibers. Following experimental membrane stress
      in vitro, dysferlin-deficient muscle fibers undergo extensive functional and
      structural disruption of the t-tubules that is ameliorated by reducing external
      [Ca(2+)] or blocking L-type Ca(2+) channels with diltiazem. Furthermore, we
      demonstrate that diltiazem treatment of dysferlin-deficient mice significantly
      reduces eccentric contraction-induced t-tubule damage, inflammation, and
      necrosis, which resulted in a concomitant increase in postinjury functional
      recovery. Our discovery of dysferlin as a t-tubule protein that stabilizes stress
      induced Ca(2+) signaling offers a therapeutic avenue for limb girdle muscular
      dystrophy 2B and Miyoshi myopathy patients. 

PMID- 24302766
TI  - Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to
      giant multinucleated Reed-Sternberg cells.
AB  - Multinucleated Reed-Sternberg (RS) cells are pathognomonic for classical Hodgkin
      lymphoma (HL), and their presence is essential for diagnosis. How these giant
      tumor cells develop is controversial, however. It has been postulated that RS
      cells arise from mononucleated Hodgkin cells via endomitosis. Conversely,
      continuous single-cell tracking of HL cell lines by long-term time-lapse
      microscopy has identified cell fusion as the main route of RS cell formation. In
      contrast to growth-induced formation of giant Hodgkin cells, fusion of small
      mononuclear cells followed by a size increase gives rise to giant RS cells. Of
      note, fusion of cells originating from the same ancestor, termed re-fusion, is
      seen nearly exclusively. In the majority of cases, re-fusion of daughter cells is
      preceded by incomplete cytokinesis, as demonstrated by microtubule bonds among
      the cells. We confirm at the level of individual tracked cells that giant Hodgkin
      and RS cells have little proliferative capacity, further supporting small
      mononuclear Hodgkin cells as the proliferative compartment of the HL tumor clone.
      In addition, sister cells show a shared propensity for re-fusion, providing
      evidence of early RS cell fate commitment. Thus, RS cell generation is related
      neither to cell fusion of unrelated Hodgkin cells nor to endomitosis, but rather
      is mediated by re-fusion of daughter cells that underwent mitosis. This
      surprising finding supports the existence of a unique mechanism for the
      generation of multinuclear RS cells that may have implications beyond HL, given
      that RS-like cells are frequently observed in several other lymphoproliferative
      diseases as well. 

PMID- 24302767
TI  - Lipid bilayer nanodisc platform for investigating polyprenol-dependent enzyme
      interactions and activities.
AB  - Membrane-bound polyprenol-dependent pathways are important for the assembly of
      essential glycoconjugates in all domains of life. However, despite their
      prevalence, the functional significance of the extended linear polyprenyl groups
      in the interactions of the glycan substrates, the biosynthetic enzymes that act
      upon them, and the membrane bilayer in which they are embedded remains a mystery.
      These interactions are investigated simultaneously and uniquely through
      application of the nanodisc membrane technology. The Campylobacter jejuni N
      linked glycosylation pathway has been chosen as a model pathway in which all of
      the enzymes and substrates are biochemically accessible. We present the
      functional reconstitution of two enzymes responsible for the early membrane
      committed steps in glycan assembly. Protein stoichiometry analysis, fluorescence
      based approaches, and biochemical activity assays are used to demonstrate the
      colocalization of the two enzymes in nanodiscs. Isotopic labeling of the
      substrates reveals that undecaprenyl-phosphate is coincorporated into discs with
      the two enzymes, and furthermore, that both enzymes are functionally
      reconstituted and can sequentially convert the coembedded undecaprenyl-phosphate
      into undecaprenyl-diphosphate-linked disaccharide. These studies provide a proof
      of-concept demonstrating that the nanodisc model membrane system represents a
      promising experimental platform for analyzing the multifaceted interactions among
      the enzymes involved in polyprenol-dependent glycan assembly pathways, the
      membrane-associated substrates, and the lipid bilayer. The stage is now set for
      exploration of the roles of the conserved polyprenols in promoting protein
      protein interactions among pathway enzymes and processing of substrates through
      sequential steps in membrane-associated glycan assembly. 

PMID- 24302769
TI  - Pomalidomide is teratogenic in rats and rabbits and can be neurotoxic in humans.

PMID- 24302768
TI  - Conditional ablation of HMGB1 in mice reveals its protective function against
      endotoxemia and bacterial infection.
AB  - High-mobility group box 1 (HMGB1) is a DNA-binding protein abundantly expressed
      in the nucleus that has gained much attention for its regulation of immunity and
      inflammation. Despite this, whether and how HMGB1 contributes to protective
      and/or pathological responses in vivo is unclear. In this study, we constructed
      Hmgb1-floxed (Hmgb1(f)(/f)) mice to achieve the conditional inactivation of the
      gene in a cell- and tissue-specific manner by crossing these mice with an
      appropriate Cre recombinase transgenic strain. Interestingly, although mice with
      HMGB1 ablation in myeloid cells apparently develop normally, they are more
      sensitive to endotoxin shock compared with control mice, which is accompanied by
      massive macrophage cell death. Furthermore, these mice also show an increased
      sensitivity to Listeria monocytogenes infection. We also provide evidence that
      the loss of HMGB1 in macrophages results in the suppression of autophagy, which
      is commonly induced by lipopolysaccharide stimulation or L. monocytogenes
      infection. Thus, intracellular HMGB1 contributes to the protection of mice from
      endotoxemia and bacterial infection by mediating autophagy in macrophages. These
      newly generated HMGB1 conditional knockout mice will serve a useful tool with
      which to study further the in vivo role of this protein in various pathological
      conditions. 

PMID- 24302770
TI  - Pomalidomide is strongly antiangiogenic and teratogenic in relevant animal
      models.

PMID- 24302771
TI  - Robust estimation of optimal dynamic treatment regimes for sequential treatment
      decisions.
AB  - A dynamic treatment regime is a list of sequential decision rules for assigning
      treatment based on a patient's history. Q- and A-learning are two main approaches
      for estimating the optimal regime, i.e., that yielding the most beneficial
      outcome in the patient population, using data from a clinical trial or
      observational study. Q-learning requires postulated regression models for the
      outcome, while A-learning involves models for that part of the outcome regression
      representing treatment contrasts and for treatment assignment. We propose an
      alternative to Q- and A-learning that maximizes a doubly robust augmented inverse
      probability weighted estimator for population mean outcome over a restricted
      class of regimes. Simulations demonstrate the method's performance and robustness
      to model misspecification, which is a key concern.

PMID- 24302772
TI  - Cervical artery dissection: a biomechanical perspective.

PMID- 24302773
TI  - The Clinical Practice Guideline Initiative: A joint collaboration designed to
      improve the quality of care delivered by doctors of chiropractic.

PMID- 24302774
TI  - Chiropractors as Primary Spine Care Providers: precedents and essential measures.
AB  - Chiropractors have the potential to address a substantial portion of spinal
      disorders; however the utilization rate of chiropractic services has remained low
      and largely unchanged for decades. Other health care professions such as
      podiatry/chiropody, physiotherapy and naturopathy have successfully gained public
      and professional trust, increases in scope of practice and distinct niche
      positions within mainstream health care. Due to the overwhelming burden of spine
      care upon the health care system, the establishment of a 'primary spine care
      provider' may be a worthwhile niche position to create for society's needs.
      Chiropractors could fulfill this role, but not without first reviewing and
      improving its approach to the management of spinal disorders. Such changes have
      already been achieved by the chiropractic profession in Switzerland, Denmark, and
      New Mexico, whose examples may serve as important templates for renewal here in
      Canada. 

PMID- 24302775
TI  - JCCA Sports Chiropractic 5(th) Issue.

PMID- 24302776
TI  - A profile of the Youth Olympic Taekwondo Athlete.
AB  - Our study aims to identify trends in anthropomorphic attributes and competitive
      strategies of successful (medalists) versus non medalist young Olympic Taekwondo
      competitors by gender in terms of body mass, body-mass index (BMI) and fighting
      technique at the Youth Olympic Games 2010. Results were then compared to adult
      Taekwondo Olympic athletes in 2000, 2004 and 2008. Data on 96 Taekwondo athletes
      were obtained from the official Youth Olympic website. A LOGIT analysis was
      performed on the following six independent variables: height, body mass, body
      mass index, gender, techniques used to score, and warnings obtained during a
      match. The study did find some differences between winners and non-winners for
      males and female, although none of the differences were statistically
      significant. Consequently, training personnel may enhance winning potential of
      Taekwondo competitors by focusing on offensive versus defensive techniques and
      improving the quality of punching. 

PMID- 24302777
TI  - A multidisciplinary approach including the use of platelet-rich plasma to treat
      an elite athlete with patellar tendinopathy - a case report.
AB  - OBJECTIVE: Patellar tendinopathy affects a substantial proportion of athletes
      involved in jumping or kicking activities. Platelet rich plasma (PRP) injections
      may be a promising treatment used in conjunction with common traditional
      therapies. CLINICAL FEATURES: Patellar tendinopathy is often the result of
      repetitive or excessive overload on the patellar tendon. Activity modification,
      cryotherapy, eccentric exercises, shockwave therapy, and PRP have been indicated
      as treatment options during various stages of this condition. INTERVENTION AND
      OUTCOME: A 23 year old female, elite track and field athlete was managed for
      patellar tendinopathy with a combination of traditional therapeutic interventions
      as well as a PRP injection. This athlete returned to pre-injury level of
      competition six months post-injection. CONCLUSION: Emerging literature on PRP
      appears to be promising for patellar tendinopathy, however, it remains unclear
      which patients may benefit most and whether the stage of the disorder has an
      impact on the clinical outcome.

PMID- 24302778
TI  - Ganglion cyst of the foot treated with electroacupuncture: A case report.
AB  - OBJECTIVE: To present the clinical management of a ganglion cyst presenting on
      the dorsolateral aspect of the foot. CLINICAL FEATURES: A 45-year-old female
      cyclist complaining of ganglion cyst following training period. INTERVENTION AND
      OUTCOME: Patient was treated with high-frequency electroacupuncture in four
      consecutive sessions over four weeks, and reported resolution of the cyst
      following therapeutic intervention. CONCLUSIONS: Ganglion cysts of the foot are
      relatively rare connective tissue tumours with variable treatment approaches.
      Electroacupuncture may be a novel and non-invasive conservative approach for the
      treatment of ganglion cysts. Further evaluation of the efficacy of such treatment
      is warranted.

PMID- 24302779
TI  - The female athlete triad: a case series and narrative overview.
AB  - OBJECTIVE: To illustrate the varying presentations of the female athlete triad
      and to inform the practitioner of the potential sequelae of this common
      condition. CLINICAL FEATURES: Four patients presented with a variety of signs and
      symptoms of the female athlete triad including low caloric intake, osteoporosis,
      amenorrhea and/or endothelial dysfunction. INTERVENTION AND OUTCOME: A
      conservative treatment approach was utilized in each case including education on
      the female athlete triad, education on increased caloric intake and a referral to
      the family physician. CONCLUSION: Health care practitioners should be aware of
      the different clinical presentations of the female athlete triad. A narrative
      review of the literature is provided to educate practitioners on the components
      of the female athlete triad, proper diagnosis and appropriate management.

PMID- 24302780
TI  - Diagnosis and rehabilitation of gastrocnemius muscle tear: a case report.
AB  - OBJECTIVE: This case study presents the epidemiology, etiology, diagnostic
      criteria, and therapeutic interventions for a common clinical condition -
      gastrocnemius injury. CLINICAL FEATURES: A 44-year old male presented with acute
      calf pain with a palpable defect, loss of range of motion, and loss of strength
      after sustaining a soft tissue injury to the lower leg. The differential
      diagnosis of tear of the medial head of the gastrocnemius was confirmed by
      physical examination and diagnostic ultrasound imaging. INTERVENTION AND OUTCOME:
      The patient was treated over a 6 week period. Initially, rehabilitation was
      approached using the PRICE principles for symptomatic relief, followed by
      stretching, strengthening, proprioception, and conditioning exercises. At 9-month
      follow-up post injury, there was no residual impairment in the gastrocnemius
      muscle function. SUMMARY: This case demonstrates the importance of epidemiology,
      clinical assessment, and the use of diagnostic ultrasound and MRI imaging in the
      diagnosis of a tear of the medial head of the gastrocnemius muscle. With an
      accurate diagnosis and comprehension of classification of muscle injuries,
      management of gastrocnemius tears is straightforward.

PMID- 24302781
TI  - Chronic recurrent multifocal osteomyelitis in a 13 year old female athlete: a
      case report.
AB  - Chronic recurrent mutlifocal osteomyelitis (CRMO) is an extremely rare skeletal
      disorder in the younger population. It presents with multifocal bony lesions that
      often mimic more sinister diagnoses such as infection or neoplasm. The cause of
      this condition remains unknown and there is limited evidence on effective
      treatments. In this case, a 13-year-old female athlete presented to a sports
      chiropractic clinic with non-traumatic onset of right ankle pain. After failed
      conservative management, radiographs and MRI were obtained exhibiting a bony
      lesion of the distal tibia resembling osteomyelitis. The patient was non
      responsive to antibiotics, which lead to the diagnosis of CRMO. CRMO should be
      considered as a differential diagnosis for chronic bone pain with affinity for
      the long bones of the lower extremity in children and adolescents. The role of
      the primary clinician in cases of CRMO is primarily that of recognition and
      referral for further diagnostic investigations. 

PMID- 24302782
TI  - Entrapment of the saphenous nerve at the adductor canal affecting the
      infrapatellar branch - a report on two cases.
AB  - OBJECTIVE: To present 2 cases of entrapment of the saphenous nerve at the
      adductor canal affecting the infrapatellar branch, and to provide insight into
      the utilization of nerve tension testing for the diagnosis of nerve entrapments
      in a clinical setting. RATIONALE: Saphenous nerve entrapments are a very rare
      condition within today's body of literature, and the diagnosis remains
      controversial. CLINICAL FEATURES: Two cases of chronic knee pain that were
      unresponsive to previous treatment. The patients were diagnosed with an
      entrapment of the saphenous nerve at the adductor canal affecting the
      infrapatellar branch using nerve tension techniques along with a full clinical
      examination. INTERVENTION AND OUTCOME: Manual therapy and rehabilitation programs
      were initiated including soft tissue therapy, nerve gliding techniques and gait
      retraining which resulted in 90% improvement in one case and complete resolution
      of symptoms in the second. CONCLUSION: Nerve tension testing may prove to be an
      aid in the diagnosis of saphenous nerve entrapments within a clinical setting in
      order to decrease time to diagnosis and proper treatment.

PMID- 24302783
TI  - Addressing the risk factors and prevention of Sudden Cardiac Death in young
      athletes: a case report.
AB  - BACKGROUND: Mandatory prescreening for the identification of risk factors and
      prevention of sudden cardiac death (SCD) is a widely debated topic within
      academic literature. In addition, the effective emergency management of sudden
      cardiac arrest (SCA) has reported lower survival outcomes (9% with bystander CPR,
      24% with AED application) although improvements, such as strategic placements of
      AED units and Hands-Only (compression only) CPR, are being made. PURPOSE: This
      case will outline the importance of establishing a true SCD incidence rate and
      the increased need for trained personal with proper equipment available to
      deliver immediate emergency cardiac management. CONCLUSION: Given the lack of
      overall expert consensus and the low survival outcomes associated with SCD, a
      true incidence rate will need to be determined prior to developing a widely
      accepted policy. Since pre-screening all young athletes does not appear to
      prevent all SCD's, having properly trained personnel and easily accessible
      equipment at sporting venues, especially in remote locations, appears to be key.

PMID- 24302784
TI  - The effects of kinesiotape on athletic-based performance outcomes in healthy,
      active individuals: a literature synthesis.
AB  - CONTEXT: The effect of the application of kinesiotape to skin overlying
      musculature on measurable athletic-based performance outcomes in healthy
      individuals has not been well established. OBJECTIVE: To systematically search
      and assess the quality of the literature on the effect of kinesiotape on athletic
      based performance outcomes in healthy, active individuals. METHODS: An electronic
      search strategy was conducted in MANTIS, Cochrane Library and EBSCO databases.
      Retrieved articles that met the eligibility criteria were rated for
      methodological quality by using an adaption of the critical appraisal criteria in
      Clinical Epidemiology by Sackett et al. RESULTS: Ten articles met the inclusion
      criteria. Seven articles had positive results in at least one athletic-based
      performance measure compared to controls. CONCLUSION: Evidence is lacking to
      support the use of kinesiotape as a successful measure for improving athletic
      based performance outcomes in healthy individuals. However, there is no evidence
      to show that kinesiotape has a negative effect on any of the performace measures.

PMID- 24302785
TI  - Nitrogen dynamics in Turbic Cryosols from Siberia and Greenland.
AB  - Turbic Cryosols (permafrost soils characterized by cryoturbation, i.e., by mixing
      of soil layers due to freezing and thawing) are widespread across the Arctic, and
      contain large amounts of poorly decomposed organic material buried in the
      subsoil. This cryoturbated organic matter exhibits retarded decomposition
      compared to organic material in the topsoil. Since soil organic matter (SOM)
      decomposition is known to be tightly linked to N availability, we investigated N
      transformation rates in different soil horizons of three tundra sites in north
      eastern Siberia and Greenland. We measured gross rates of protein
      depolymerization, N mineralization (ammonification) and nitrification, as well as
      microbial uptake of amino acids and NH4+ using an array of 15N pool dilution
      approaches. We found that all sites and horizons were characterized by low N
      availability, as indicated by low N mineralization compared to protein
      depolymerization rates (with gross N mineralization accounting on average for 14%
      of gross protein depolymerization). The proportion of organic N mineralized was
      significantly higher at the Greenland than at the Siberian sites, suggesting
      differences in N limitation. The proportion of organic N mineralized, however,
      did not differ significantly between soil horizons, pointing to a similar N
      demand of the microbial community of each horizon. In contrast, absolute N
      transformation rates were significantly lower in cryoturbated than in organic
      horizons, with cryoturbated horizons reaching not more than 32% of the
      transformation rates in organic horizons. Our results thus indicate a
      deceleration of the entire N cycle in cryoturbated soil horizons, especially
      strongly reduced rates of protein depolymerization (16% of organic horizons)
      which is considered the rate-limiting step in soil N cycling.

PMID- 24302786
TI  - A comparison of two colorimetric assays, based upon Lowry and Bradford
      techniques, to estimate total protein in soil extracts.
AB  - Soil extracts usually contain large quantities of dissolved humified organic
      material, typically reflected by high polyphenolic content. Since polyphenols
      seriously confound quantification of extracted protein, minimising this
      interference is important to ensure measurements are representative. Although the
      Bradford colorimetric assay is used routinely in soil science for rapid
      quantification protein in soil-extracts, it has several limitations. We therefore
      investigated an alternative colorimetric technique based on the Lowry assay
      (frequently used to measure protein and humic substances as distinct pools in
      microbial biofilms). The accuracies of both the Bradford assay and a modified
      Lowry microplate method were compared in factorial combination. Protein was
      quantified in soil-extracts (extracted with citrate), including standard
      additions of model protein (BSA) and polyphenol (Sigma H1675-2). Using the Lowry
      microplate assay described, no interfering effects of citrate were detected even
      with concentrations up to 5 times greater than are typically used to extract soil
      protein. Moreover, the Bradford assay was found to be highly susceptible to two
      simultaneous and confounding artefacts: 1) the colour development due to added
      protein was greatly inhibited by polyphenol concentration, and 2) substantial
      colour development was caused directly by the polyphenol addition. In contrast,
      the Lowry method enabled distinction between colour development from protein and
      non-protein origin, providing a more accurate quantitative analysis. These
      results suggest that the modified-Lowry method is a more suitable measure of
      extract protein (defined by standard equivalents) because it is less confounded
      by the high polyphenolic content which is so typical of soil extracts.

PMID- 24302787
TI  - Efficiency of bulk-heterojunction organic solar cells.
AB  - During the last years the performance of bulk heterojunction solar cells has been
      improved significantly. For a large-scale application of this technology further
      improvements are required. This article reviews the basic working principles and
      the state of the art device design of bulk heterojunction solar cells. The
      importance of high power conversion efficiencies for the commercial exploitation
      is outlined and different efficiency models for bulk heterojunction solar cells
      are discussed. Assuming state of the art materials and device architectures
      several models predict power conversion efficiencies in the range of 10-15%. A
      more general approach assuming device operation close to the Shockley-Queisser
      limit leads to even higher efficiencies. Bulk heterojunction devices exhibiting
      only radiative recombination of charge carriers could be as efficient as ideal
      inorganic photovoltaic devices.

PMID- 24302788
TI  - A phylogenetic re-evaluation of Phyllosticta (Botryosphaeriales).
AB  - Phyllosticta is a geographically widespread genus of plant pathogenic fungi with
      a diverse host range. This study redefines Phyllosticta, and shows that it
      clusters sister to the Botryosphaeriaceae (Botryosphaeriales, Dothideomycetes),
      for which the older family name Phyllostictaceae is resurrected. In moving to a
      unit nomenclature for fungi, the generic name Phyllosticta was chosen over
      Guignardia in previous studies, an approach that we support here. We use a
      multigene DNA dataset of the ITS, LSU, ACT, TEF and GPDH gene regions to
      investigate 129 isolates of Phyllosticta, representing about 170 species names,
      many of which are shown to be synonyms of the ubiquitous endophyte P.
      capitalensis. Based on the data generated here, 12 new species are introduced,
      while epitype and neotype specimens are designated for a further seven species.
      One species of interest is P. citrimaxima associated with tan spot of Citrus
      maxima fruit in Thailand, which adds a fifth species to the citrus black spot
      complex. Previous morphological studies lumped many taxa under single names that
      represent complexes. In spite of this Phyllosticta is a species-rich genus, and
      many of these taxa need to be recollected in order to resolve their phylogeny and
      taxonomy. TAXONOMIC NOVELTIES: New species - Phyllosticta abieticola Wikee &
      Crous, P. aloeicola Wikee & Crous, P. citrimaxima Wikee, Crous, K.D. Hyde &
      McKenzie, P. leucothoicola Wikee, Motohashi & Crous, P. mangifera-indica Wikee,
      Crous, K.D. Hyde & McKenzie, P. neopyrolae Wikee, Motohashi, Crous, K.D. Hyde &
      McKenzie, P. pachysandricola Wikee, Motohashi & Crous, P. paxistimae Wikee &
      Crous, P. podocarpicola Wikee, Crous, K.D. Hyde & McKenzie, P. rhaphiolepidis
      Wikee, C. Nakash. & Crous, P. rubra Wikee & Crous, P. vacciniicola Wikee, Crous,
      K.D. Hyde & McKenzie; New combinations - P. foliorum (Sacc.) Wikee & Crous, P.
      philoprina (Berk. & M.A. Curtis) Wikee & Crous; Epitypifications (basionyms) - P.
      concentrica Sacc., P. cussoniae Cejp, P. owaniana G. Winter; Neotypifications
      (basionyms) - Phyllosticta cordylinophila P.A. Young, Physalospora gregaria var.
      foliorum Sacc., Sphaeropsis hypoglossi Mont., Sphaeropsis minima Berk. & M.A.
      Curtis.

PMID- 24302789
TI  - Phylogenetic lineages in the Botryosphaeriales: a systematic and evolutionary
      framework.
AB  - The order Botryosphaeriales represents several ecologically diverse fungal
      families that are commonly isolated as endophytes or pathogens from various woody
      hosts. The taxonomy of members of this order has been strongly influenced by
      sequence-based phylogenetics, and the abandonment of dual nomenclature. In this
      study, the phylogenetic relationships of the genera known from culture are
      evaluated based on DNA sequence data for six loci (SSU, LSU, ITS, EF1, BT,
      mtSSU). The results make it possible to recognise a total of six families. Other
      than the Botryosphaeriaceae (17 genera), Phyllostictaceae (Phyllosticta) and
      Planistromellaceae (Kellermania), newly introduced families include
      Aplosporellaceae (Aplosporella and Bagnisiella), Melanopsaceae (Melanops), and
      Saccharataceae (Saccharata). Furthermore, the evolution of morphological
      characters in the Botryosphaeriaceae were investigated via analysis of phylogeny
      trait association. None of the traits presented a significant phylogenetic
      signal, suggesting that conidial and ascospore pigmentation, septation and
      appendages evolved more than once in the family. Molecular clock dating on
      radiations within the Botryosphaeriales based on estimated mutation rates of the
      rDNA SSU locus, suggests that the order originated in the Cretaceous period
      around 103 (45-188) mya, with most of the diversification in the Tertiary period.
      This coincides with important periods of radiation and spread of the main group
      of plants that these fungi infect, namely woody Angiosperms. The resulting host
      associations and distribution could have influenced the diversification of these
      fungi. TAXONOMIC NOVELTIES: New families - Aplosporellaceae Slippers, Boissin &
      Crous, Melanopsaceae Phillips, Slippers, Boissin & Crous, Saccharataceae
      Slippers, Boissin & Crous.

PMID- 24302790
TI  - The Botryosphaeriaceae: genera and species known from culture.
AB  - In this paper we give an account of the genera and species in the
      Botryosphaeriaceae. We consider morphological characters alone as inadequate to
      define genera or identify species, given the confusion it has repeatedly
      introduced in the past, their variation during development, and inevitable
      overlap as representation grows. Thus it seems likely that all of the older taxa
      linked to the Botryosphaeriaceae, and for which cultures or DNA sequence data are
      not available, cannot be linked to the species in this family that are known from
      culture. Such older taxa will have to be disregarded for future use unless they
      are epitypified. We therefore focus this paper on the 17 genera that can now be
      recognised phylogenetically, which concentrates on the species that are presently
      known from culture. Included is a historical overview of the family, the
      morphological features that define the genera and species and detailed
      descriptions of the 17 genera and 110 species. Keys to the genera and species are
      also provided. Phylogenetic relationships of the genera are given in a multi
      locus tree based on combined SSU, ITS, LSU, EF1-alpha and beta-tubulin sequences.
      The morphological descriptions are supplemented by phylogenetic trees (ITS alone
      or ITS + EF1-alpha) for the species in each genus. TAXONOMIC NOVELTIES: New
      species - Neofusicoccum batangarum Begoude, Jol. Roux & Slippers. New
      combinations - Botryosphaeria fabicerciana (S.F. Chen, D. Pavlic, M.J. Wingf. &
      X.D. Zhou) A.J.L. Phillips & A. Alves, Botryosphaeria ramosa (Pavlic, T.I.
      Burgess, M.J. Wingf.) A.J.L. Phillips & A. Alves, Cophinforma atrovirens (Mehl &
      Slippers) A. Alves & A.J.L. Phillips, Cophinforma mamane (D.E. Gardner) A.J.L.
      Phillips & A. Alves, Dothiorella pretoriensis (Jami, Gryzenh., Slippers & M.J.
      Wingf.) Abdollahz. & A.J.L. Phillips, Dothiorella thailandica (D.Q. Dai., J.K.
      Liu & K.D. Hyde) Abdollahz., A.J.L. Phillips & A. Alves, Dothiorella uruguayensis
      (C.A. Perez, Blanchette, Slippers & M.J. Wingf.) Abdollahz. & A.J.L. Phillips,
      Lasiodiplodia lignicola (Ariyawansa, J.K. Liu & K.D. Hyde) A.J.L. Phillips, A.
      Alves & Abdollahz., Neoscytalidium hyalinum (C.K. Campb. & J.L. Mulder) A.J.L.
      Phillips, Groenewald & Crous, Sphaeropsis citrigena (A.J.L. Phillips, P.R.
      Johnst. & Pennycook) A.J.L. Phillips & A. Alves, Sphaeropsis eucalypticola
      (Doilom, J.K. Liu, & K.D. Hyde) A.J.L. Phillips, Sphaeropsis porosa (Van Niekerk
      & Crous) A.J.L. Phillips & A. Alves. Epitypification (basionym) - Sphaeria
      sapinea Fries. Neotypifications (basionyms) - Botryodiplodia theobromae Pat.,
      Physalospora agaves Henn, Sphaeria atrovirens var. visci Alb. & Schwein.

PMID- 24302791
TI  - Texture and topography analysis of doxycycline hyclate thermosensitive systems
      comprising zinc oxide.
AB  - To characterize the thermal behavior and texture analysis of doxycycline hyclate
      thermosensitive gels developed for periodontitis treatment containing zinc oxide
      prepared by using poloxamer (Lutrol((r)) F127) as polymeric material and N-methyl
      pyrrolidone was used as cosolvent. The thermosensitive gel comprising doxycycline
      hyclate, Lutrol((r)) F127, and N-methyl pyrrolidone were characterized for the
      thermal behavior and texture analysis. The topography of the system after the
      dissolution test was characterized with scanning electron microscope.
      Differential scanning calorimetric thermogram exhibited the endothermic peaks in
      the systems containing high amount of N-methyl pyrrolidone in solvent. The sol
      gel transition temperature of the systems decreased as the zinc oxide amount was
      increased. The addition of doxycycline hyclate, zinc oxide, and N-methyl
      pyrrolidone affected the syringeability of systems. The addition of zinc oxide
      into the doxycycline hyclate-Lutrol((r)) F127 systems decreased the diameter of
      inhibition zone against Staphylococcus aureus, Escherichia coli, and Candida
      albicans since zinc oxide decreased the diffusion and prolonged release of
      doxycycline hyclate. From scanning electron microscope analysis, the porous
      surface of 20% w/w Lutrol((r)) F127 system was notably different from that of gel
      comprising doxycycline hyclate which had interconnected pores and smooth
      surfaces. The number of pores was decreased with increasing zinc oxide and the
      porous structure was smaller and more compact. Therefore, the addition of zinc
      oxide could increase the syringeability of doxycycline hyclate-Lutrol((r)) F127
      system with the temperature dependence. Zinc oxide decreased inhibition zone
      against test microbes because of prolongation of doxycycline hyclate release and
      reduced size of continuous cells. Furthermore, zinc oxide also increased the
      compactness of wall surfaces of Lutrol((r)) F127. 

PMID- 24302792
TI  - Immunostimulant Activity of a Novel Polysaccharide Isolated from Lactarius
      deliciosus (L. ex Fr.) Gray.
AB  - More and more fungal polysaccharides have been reported to exhibit a variety of
      biological activities, including antitumor, antioxidant and immunostimulant
      activity. The non-starch polysaccharides have emerged as an important class of
      bioactive natural products. In this study, the immune activities of a novel
      polysaccharide (LDG-A) isolated from Lactarius deliciosus (L. ex Fr.) Gray were
      investigated at 20, 40 and 80 mg/kg dose levels. The inhibitory rate in mice
      treated with 80 mg/kg LDG-A can reach 68.422%, being the highest in the three
      doses, which may be comparable to mannatide. Histology of immune organs showed
      that the tissues were arranged in more regular and firm pattern, but the tumor
      tissue arranged looser in LDG-A group than those in control group. Meanwhile,
      there was no obvious damage to other organs, such as heart, lung, and kidney. The
      antitumor activity of the LDG-A was usually believed to be a consequence of the
      stimulation of the cell-mediated immune response because it can significantly
      promote the lymphocyte and macrophage cells in the dose range of 50-200 MUg/ml
      and 100-400 MUg/ml in vitro, respectively. The level of cytokines (IL-6, TNF
      alpha, and NO) of macrophage cells induced by LDG-A treatment was similar to
      lipopolysaccharides at different concentrations. The expression of all these
      genes studied (TNF-alpha, IL-6, and iNOS mRNA) in the untreated macrophage was
      little, but increased dramatically in a dose-dependent manner in the LDG-A
      treated cells. The results obtained in the present study indicated that the
      purified polysaccharide of L. deliciosus (L. ex Fr.) Gray is a potential source
      of natural immune-stimulating substances. 

PMID- 24302793
TI  - The Effect of Hydroethanol Extract of Achillea Millefolium on beta-adrenoceptors
      of Guinea Pig Tracheal Smooth Muscle.
AB  - Different pharmacological effects of Achillea millefolium including its relaxant
      effect on smooth muscle have been shown previously. In the present study the
      stimulatory effect of the plant extract on beta-adrenoceptor of tracheal muscle
      was examined in order to investigate one possible mechanism for its observed
      relaxant effect. Effect of three concentrations of hydroethanol extract, 10 nM
      propranolol, and saline on beta-adrenoceptor was tested in two experimental
      groups including; nonincubated tracheal smooth muscles (group 1) and incubated
      tracheal smooth muscle with chlorpheniramine (group 2). Concentration response
      curves to isoprenaline were performed in precontracted tracheal smooth muscle in
      the presence of the extract, propranolol and saline. Values of EC50 and CR-1 were
      measured. Leftward shifts in isoprenaline curves were observed in the presence of
      medium and high concentrations of the extract compared with saline in both
      groups. The values of EC50 obtained in the presence of medium and high
      concentrations of the extract only in group 1 were nonsignificantly lower than
      that of saline. The values of CR-1 obtained in the presence of all concentrations
      of the extract in both groups were negative and significantly different with that
      of propranolol. The results indicated a small stimulatory effect of the extract
      on beta2-adrenoceptors. 

PMID- 24302794
TI  - Mutual Amide Prodrug of Etodolac-glucosamine: Synthesis, Characterization and
      Pharmacological Screening.
AB  - Etodolac, a nonsteroidal antiinflammatory drug, widely used in arthritis is
      associated with gastric ulceration and irritation due to presence of free
      carboxylic group. The current investigation reports synthesis of mutual amide
      prodrug of etodolac by masking free carboxylic group with glucosamine, a
      nutritional supplement for treatment of arthritis. Confirmation and
      characterization of the structure of the synthesized prodrug done by elemental
      and spectroscopy analysis, melting point, determination of migration parameters
      (Rf, RM, and Rt) by using thin layer chromatography and high performance liquid
      chromatography, respectively. Partition coefficient and solubility study confirms
      its lipophilic character so can be suitable candidate for controlled release
      delivery. In vitro hydrolytic studies of prodrug confirms good rate of hydrolysis
      in blood plasma, fecal matter, and simulated intestinal fluid while stable in
      gastric simulated fluid. In vivo pharmacological screening performed on animals.
      Prodrug with respect to etodolac shows good analgesic, antiinflammatory, and
      antiarthritic activity. The prodrug was assessed for their probable damaging
      effects by ulcerogeniticity and histopathological analysis. The histopathological
      studies showed less ulceration in the gastric region when treated with prodrug,
      thereby proving the prodrug to be better in action as compared to etodolac and
      are advantageous in having less gastrointestinal side effects. 

PMID- 24302795
TI  - Stability-indicating HPLC Method for Simultaneous Determination of Aspirin and
      Prasugrel.
AB  - A simple, sensitive, specific, accurate, and stability-indicating reversed phase
      high performance liquid chromatographic method was developed for the simultaneous
      determination of aspirin and prasugrel, using a Kromasil 100 C18 (150*4.6 mm, 5
      MU) column and a mobile phase composed of acetonitrile:methanol:water (30:10:60,
      v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of aspirin and
      prasugrel were found to be 3.28 min and 6.61 min, respectively. Linearity was
      established for aspirin and prasugrel in the range of 15-150 and 2-20 MUg/ml,
      respectively. The percentage recoveries of aspirin and prasugrel were found to be
      in the range of 99.34-100.32% and 98.92-102.09%, respectively. Both the drugs
      were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, and
      UV degradation. The degradation studies indicated aspirin to be more susceptible
      to alkaline hydrolysis, while prasugrel to be more susceptible to neutral
      hydrolysis. The degradation products were well resolved from the pure drug with
      significant differences in their retention time values. This method can be
      successfully employed for simultaneous quantitative analysis of aspirin and
      prasugrel in bulk drugs and formulations. 

PMID- 24302796
TI  - Optimization of Paclitaxel Containing pH-Sensitive Liposomes By 3 Factor, 3 Level
      Box-Behnken Design.
AB  - The aim of this study was to investigate the combined influence of 3 independent
      variables in the preparation of paclitaxel containing pH-sensitive liposomes. A 3
      factor, 3 levels Box-Behnken design was used to derive a second order polynomial
      equation and construct contour plots to predict responses. The independent
      variables selected were molar ratio
      phosphatidylcholine:diolylphosphatidylethanolamine (X1), molar concentration of
      cholesterylhemisuccinate (X2), and amount of drug (X3). Fifteen batches were
      prepared by thin film hydration method and evaluated for percent drug entrapment,
      vesicle size, and pH sensitivity. The transformed values of the independent
      variables and the percent drug entrapment were subjected to multiple regression
      to establish full model second order polynomial equation. F was calculated to
      confirm the omission of insignificant terms from the full model equation to
      derive a reduced model polynomial equation to predict the dependent variables.
      Contour plots were constructed to show the effects of X1, X2, and X3 on the
      percent drug entrapment. A model was validated for accurate prediction of the
      percent drug entrapment by performing checkpoint analysis. The computer
      optimization process and contour plots predicted the levels of independent
      variables X1, X2, and X3 (0.99, -0.06, 0, respectively), for maximized response
      of percent drug entrapment with constraints on vesicle size and pH sensitivity. 

PMID- 24302797
TI  - Biochemical Evaluation of the Hypoglycemic Effects of Extract and Fraction of
      Cassia fistula Linn. in Alloxan-induced Diabetic Rats.
AB  - Various extracts of flowers of Cassia fistula Linn (Leguminosae) such as
      petroleum ether (60-80 degrees ), chloroform, acetone, ethanol, aqueous, and
      crude aqueous extracts and two fractions of ethanol extract were tested for
      antihyperglycemic activity in glucose-overloaded hyperglycemic rats. The
      effective antihyperglycemic extracts and fraction were tested for their
      hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To
      confirm their utility in higher models, the effective extracts and fraction of C.
      fistula were subjected to antidiabetic study in an alloxan-induced diabetic model
      at two dose levels, 200 and 400 mg/kg, respectively. Biochemical parameters like
      glucose, urea, creatinine, serum cholesterol, serum triglyceride, high-density
      lipoprotein, low-density lipoprotein, hemoglobin, and glycosylated hemoglobin
      were also assessed in experimental animals. The petroleum ether and ethanol
      extracts of C. fistula and the water-soluble fraction of ethanol extract were
      found to exhibit significant antihyperglycemic activity. The extracts, at the
      given doses, did not produce hypoglycemia in fasted normal rats, and the fraction
      exhibited weak hypoglycemic effect after 2 h of the treatment. Treatment of
      diabetic rats with ethanol extract and water-soluble fraction of this plant
      restored the elevated biochemical parameters significantly (P<0.05) to the normal
      level. No activity was found in the petroleum ether extract of the plant.
      Comparatively, the water-soluble fraction of ethanol extract was found to be more
      effective than the ethanol extract, and the activity was comparable with that of
      the standard, glibenclamide (5 mg/kg). 

PMID- 24302798
TI  - Rheological characterization of an acetaminophen jelly.
AB  - The aim of this study was to prepare an inclusion complex of acetaminophen and
      beta-cyclodextrin (molar ratio of 1:1). A jelly with inclusion complexes formed
      by kneading was prepared. The formation of inclusion complexes was assessed by
      powder X-ray diffraction patterns and Fourier transform-infrared spectroscopy.
      Jellies were prepared with xanthan gum, gelatin, and kappa-carrageenan. The
      concentration of each jelling agent was 0.5, 1.0, and 1.5% w/v. Viscoelasticity
      and dissolution characteristics were determined and osmometry was performed.
      PGWater(TM), a commercial jelly for fluid replacement, served as a reference for
      viscoelastic characteristics and dissolution. Powder X-ray diffraction
      measurement revealed a different diffraction pattern for the kneading than for
      acetaminophen and beta-cyclodextrin. Fourier transform-infrared spectroscopy
      revealed an absorption peak (at around 1655 cm(-1)) due to the carbonyl group and
      benzene ring (at around 1610 cm(-1)) of acetaminophen. In contrast, the kneaded
      mixture (1:1) had a shift in the absorption peak due to the carbonyl group (at
      around 1650 cm(-1)) in acetaminophen's molecular structure, and the formation of
      an inclusion complex was noted. The viscosity of xanthan gum-1.0, gelatin-1.5,
      and carrageenan-0.5 resembled the viscoelasticity of PGWater(TM). The
      acetaminophen in gelatin-1.0 and carrageenan-0.5 had dissolution behavior similar
      to that of commercial acetaminophen preparations. The osmolality of jellies
      prepared in different concentrations ranged from about 20-50 mOsm/kg. Results
      suggested that carrageenan-0.5 could serve as a useful jelly vehicle for
      acetaminophen. 

PMID- 24302799
TI  - Alginate nanoparticles as a promising adjuvant and vaccine delivery system.
AB  - During last decades, diphtheria has remained as a serious disease that still
      outbreaks and can occur worldwide. Recently, new vaccine delivery systems have
      been developed by using the biodegradable and biocompatible polymers such as
      alginate. Alginate nanoparticles as a carrier with adjuvant and prolong release
      properties that enhance the immunogenicity of vaccines. In this study diphtheria
      toxoid loaded nanoparticles were prepared by ionic gelation technique and
      characterized with respect to size, zeta potential, morphology, encapsulation
      efficiency, release profile, and immunogenicity. Appropriate parameters (calcium
      chloride and sodium alginate concentration, homogenization rate and
      homogenization time) redounded to the formation of suitable nanoparticles with a
      mean diameter of 70+/-0.5 nm. The loading studies of the nanoparticles resulted
      in high loading capacities (>90%) and subsequent release studies showed prolong
      profile. The stability and antigenicity of toxoid were evaluated by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and ouchterlony test and
      proved that the encapsulation process did not affect the antigenic integrity and
      activity. Guinea pigs immunized with the diphtheria toxoid-loaded alginate
      nanoparticles showed highest humoral immune response than conventional vaccine.
      It is concluded that, with regard to the desirable properties of nanoparticles
      and high immunogenicity, alginate nanoparticles could be considered as a new
      promising vaccine delivery and adjuvant system. 

PMID- 24302800
TI  - Meltlets((r)) of soy isoflavones: process optimization and the effect of
      extrusion spheronization process parameters on antioxidant activity.
AB  - In the current research work an attempt was made to develop "Melt in mouth
      pellets" (Meltlets((r))) containing 40% herbal extract of soy isoflavones that
      served to provide antioxidants activity in menopausal women. The process of
      extrusion-spheronization was optimized for extruder speed, extruder screen size,
      spheronization speed, and time. While doing so the herbal extract incorporated in
      the pellet matrix was subjected to various processing conditions such as the
      effect of the presence of other excipients, mixing or kneading to prepare wet
      mass, heat generated during the process of extrusion, spheronization, and drying.
      Thus, the work further investigates the effect of these processing parameters on
      the antioxidant activity of the soy isoflavone herbal extract incorporated in the
      formula. Thereby, the antioxidant activity of the soya bean herbal extract,
      Meltlets((r)) and of the placebo pellets was evaluated using DPPH free radical
      scavenging assay and total reduction capacity. 

PMID- 24302801
TI  - Chemical Composition, In Vitro Antimicrobial and Antioxidant Activities of the
      Essential Oils of Ocimum Gratissimum, O. Sanctum and their Major Constituents.
AB  - The essential oils of the flowering aerial parts of two Ocimum species viz.,
      Ocimum gratissimum and O. sanctum were analyzed by gas chromatography and gas
      chromatography/mass spectroscopy. The principal constituent of O. gratissimum and
      O. sanctum was eugenol (75.1%) and methyl eugenol (92.4%), comprising 99.3 and
      98.9% of the total oils, respectively. In vitro antimicrobial activity of the
      essential oils of O. gratissimum, O. sanctum and their major compounds eugenol
      and methyl eugenol were screened by using tube dilution methods. O. gratissimum
      oil was found highly active against S. marcescens while O. sanctum oil showed
      significant activity against A. niger and S. faecalis. Methyl eugenol exhibited
      significant activity against P. aeruginosa while eugenol was effective only
      against S. aureus. Antioxidant activity of oils, eugenol, and methyl eugenol was
      determined by 2,2-diphenyl-1-picrylhydrazyl and 2,2'- azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) assays. Essential oil of O. gratissimum
      showed comparative antioxidant activity with IC50 values 23.66+/-0.55 and 23.91+/
      0.49 MUg/ml in 2,2-diphenyl-1-picrylhydrazyl and 2,2'- azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) models, respectively. Eugenol showed
      slightly weaker antioxidant activity compared to oil of O. gratissimum, while O.
      sanctum oil demonstrated very feeble antioxidant activity and methyl eugenol did
      not show any activity. Eugenol and methyl eugenol would be elite source from O.
      gratissimum and O. sanctum, respectively, of this region could be consider as a
      source of natural food antioxidant, preservatives, and as an antiseptic. 

PMID- 24302802
TI  - Synthesis, SAR Study and Evaluation of Mannich and Schiff Bases of Pyrazol-5(4H)
      one Moiety Containing 3-(Hydrazinyl)-2-phenylquinazolin-4(3H)-one.
AB  - In the present investigation, a series of 12 Mannich bases (QP1-12) and 5 Schiff
      bases (QSP1-5) of pyrazol-5(4H)-one moiety containing 3-(hydrazinyl)-2
      phenylquinazolin-4(3H)-one has been synthesized and characterized by
      physicochemical as well as spectral means. The synthesized Mannich and Schiff
      bases were screened for their preliminary antimicrobial activity against Gram
      positive and Gram-negative bacterial as well as fungal strains by the
      determination of zone of inhibition. Mannich bases (QP1-12) were found to be more
      potent antibacterial agents against Gram-positive bacteria, whereas Schiff bases
      (QSP1-5) were more potent against Gram-negative bacteria and fungi. Minimum
      inhibitory concentration result demonstrated that Mannich base compound (QP7)
      having ortho -OH and para -COOH group showed some improvement in antibacterial
      activity (minimum inhibitory concentration of 48.88*10(-3) MUM/ml) among the
      tested Gram-positive organisms and it also exhibit minimum inhibitory
      concentration of value of 12.22*10(-3) MUM/ml for Klebsiella pneumoniae. The
      antitubercular activity of synthesized compounds against Mycobacterium
      tuberculosis (H37Rv) was determined using microplate alamar blue assay. Compound
      QP11 showed appreciable antitubercular activity (minimum inhibitory concentration
      of 6.49*10(-3) MUM/ml) which was more active than the standard drugs, ethambutol
      (minimum inhibitory concentration of 7.60*10(-3) MUM/ml) and ciprofloxacin
      (9.4*10(-3) MUM/ml). Compounds QP11, QP9, QSP1, QSP2, and QSP5 have good
      selective index and may be selected as a lead compound for the development of
      novel antitubercular agents. 

PMID- 24302803
TI  - Development and Validation of RP-HPLC Method for Simultaneous Estimation of
      Picroside I, Plumbagin, and Z-guggulsterone in Tablet Formulation.
AB  - The aim of the present work was to develop and validate a reversed-phase high
      performance liquid chromatography method for the simultaneous estimation of
      picroside I, plumbagin, and Z-guggulsterone in a polyherbal formulation
      containing Picrorhiza kurroa, Plumbago zeylanica, and Commiphora wightii
      extracts. The analysis was performed on a C18 column using the mobile phase
      consisting of solvent A (acetonitrile) and solvent B (0.1% orthophosphoric acid
      in water) with the following gradient: 0-12 min, 25% A; 12-17 min, 25-80% A; 17
      32 min, 80% A; and 32-37 min, 80-25% A at a flow rate of 1 ml/min. Ultraviolet
      detection was at 255 nm. The method was validated for accuracy, precision,
      linearity, specificity, and sensitivity as per the norms of the International
      Conference on Harmonization. From the validation study, it was found that the
      method is specific, accurate, precise, reliable, and reproducible. Good linear
      correlation coefficients (r(2)>0.900) were obtained for calibration plots in the
      ranges tested. Limits of detection were 2.700, 0.090 and 0.099 MUg/ml and limits
      of quantification were 9.003, 0.310, and 0.330 MUg/ml for picroside I, plumbagin,
      and Z-guggulsterone, respectively. Intra and interday relative standard deviation
      (RSD) of retention times and peak areas was less than 3.0%. Recovery was found to
      be 100.21% for picroside I, 102.5% for plumbagin, and 103.84% for Z
      guggulsterone. The established method was appropriate and the three markers were
      well resolved, enabling efficient quantitative analysis of picroside I, plumbagin
      and Z-guggulsterone. The method is a rapid and cost-effective quality control
      tool for routine quantitative analysis of picroside I, plumbagin, and Z
      guggulsterone in tablet dosage form. 

PMID- 24302804
TI  - Phenolic Contents and Antioxidant Properties from Aerial Parts of Achyranthes
      coynei Sant.
AB  - Aim of the study was to evaluate antioxidant activity and total phenolic content
      of Achyranthes coynei; an endemic plant used in treatment of several diseases in
      the same lines that of Achyranthes aspera by traditional practitioners of Belgaum
      region. Efficiency of extraction methods was studied for aerial parts (leaves,
      stem, and inflorescence) extracted in methanol using continuous shaking,
      microwave assisted and ultra sonic extraction technique, by exposing it for
      different time period. Total phenolic content was measured by Folin-Ciocalteu
      method and antioxidant activity using 2,2'-diphenyl-1-picryl hydrazyl radical
      scavenging assay and ferric reducing antioxidant power assay. Extracts of A.
      coynei revealed highest yield of total phenolic content in continuous shaking
      method compared to other methods. Significantly higher amount of phenolic content
      (467.07+/-23.35 tannic acid equivalent and 360.83+/-18.04 caffic acid equivalent
      mg/100 g FW) was estimated at 360 min of continuous shaking extraction. In 2,2'
      diphenyl-1-picryl hydrazyl radical scavenging assay and ferric reducing
      antioxidant power assay, inflorescence and leaf showed highest potential
      activity, respectively. Stem extracts showed lower yield of total phenolic
      content and antioxidant activity. Results also showed 2,2'-diphenyl-1-picryl
      hydrazyl radical scavenging assay had significant correlation with total phenolic
      content. This is first report of total phenolic content and antioxidant studies
      in A. coynei. 

PMID- 24302805
TI  - Development and Validation of High-performance Thin Layer Chromatographic Method
      for Ursolic Acid in Malus domestica Peel.
AB  - Ursolic acid, a pentacyclic triterpenoid possess a wide range of pharmacological
      activities. It shows hypoglycemic, antiandrogenic, antibacterial,
      antiinflammatory, antioxidant, diuretic and cynogenic activity. It is commonly
      present in plants especially coating of leaves and fruits, such as apple fruit,
      vinca leaves, rosemary leaves, and eucalyptus leaves. A simple high-performance
      thin layer chromatographic method has been developed for the quantification of
      ursolic acid from apple peel (Malus domestica). The samples dissolved in methanol
      and linear ascending development was carried out in twin trough glass chamber.
      The mobile phase was selected as toluene:ethyl acetate:glacial acetic acid
      (70:30:2). The linear regression analysis data for the calibration plots showed
      good linear relationship with r(2)=0.9982 in the concentration range 0.2-7
      MUg/spot with respect to peak area. According to the ICH guidelines the method
      was validated for linearity, accuracy, precision, and robustness. Statistical
      analysis of the data showed that the method is reproducible and selective for the
      estimation of ursolic acid. 

PMID- 24302806
TI  - Influence of Phenological Stages on Yield and Quality of Oregano (Origanum
      vulgare L.) Under the Agroclimatic Condition of Doon Valley (Uttarakhand).
AB  - A field experiment was conducted under the agroclimatic conditions of Doon
      valley, in order to determine the effects of phenological stages on herbage yield
      and quality of oil in oregano (Origanum vulgare L.). Plants were harvested in
      five phenological stages, i.e. early vegetative, late vegetative, flower
      initiation, full bloom, and fruit set stages. Results showed the significant
      effects of phenological stages on herbage, yield, and quality of oregano.
      Harvesting at full bloom stage showed better results in terms of herbage and oil
      yield. The quality of essential oil was evaluated using GC and GC/MS. Thymol
      content was rich in all the stages (46.90-62.26%) followed by gamma-terpinene
      (1.11-11.75%) and p-cymene (3.11-5.32%). 

PMID- 24302807
TI  - A Validated High-performance Liquid Chromatograhy Method for Estimation of
      Ferulic Acid in Asafoetida and Polyherbal Preparation.
AB  - A high-performance liquid chromatography method was developed for the estimation
      of ferulic acid from asafoetida and a polyherbal preparation. The separation was
      carried out on HiQSil ODS C-18 column with a mobile phase of acetonitrile: 10%
      acetic acid (20:80 v/v). The developed method was validated as per International
      Conference of Harmonization guidelines for various parameters such as accuracy,
      precision, linearity, limit of detection, limit of quantification and
      specificity; and found to be reliable. Linear regression analysis showed a good
      corelation between peak area and concentration with a corelation coefficient
      r(2)=0.996 in the range 200-7000 ng/ml. The developed method can be utilized for
      standardization of herbal formulation comprising asafoetida. 

PMID- 24302808
TI  - Synthesis, Characterization and In Vitro Antimicrobial Evaluation of Novel
      Pyrazolothiazol-4(5H)-one Derivatives.
AB  - Antimicrobial screening of several novel pyrazolothiazol-4(5H)-one derivatives
      (3a-3j) has been performed. Reaction of aromatic aldehydes with aromatic ketones
      yielded starting chalcones (1a-1j) which have been subsequently reacted with
      thiosemicarbazide for obtaining N-thiocarbamoylpyrazole derivatives (2a-2j).
      These were further cyclized to pyrazolothiazol-4(5H)-one derivatives (3a-3j) in
      the presence of ethylbromoacetate. The structures of newly synthesized compounds
      were confirmed by FTIR and (1)H NMR and/or MS. The in vitro antimicrobial
      activity of these compounds was evaluated against Gram positive bacteria, Gram
      negative bacteria and fungi. Their minimum inhibitory concentration was
      determined by tube dilution method. The results showed that most of the compounds
      have promising antimicrobial activity as compared to standard drugs. Among the
      test compounds, 2-[5(4-chlorophenyl)-3-phenyl-4,5-dihydropyrazol-1-yl]-thiazol
      4(5H)-one (3e) was found to show the most potent antimicrobial activity. 

PMID- 24302809
TI  - Effect of surgical treatment on lipid peroxidation parameters and antioxidant
      status in the serum of patients with peripheral arterial disease.
AB  - The various risk factors for peripheral arterial disease (PAD) are almost
      identical to those for atherosclerosis and include abnormal levels of lipids or
      lipoproteins. Lipid peroxidation parameters and total antioxidant capacity in the
      serum of male patients with PAD before surgery as well as 3-5 days and 7-10 days
      after surgery were measured. We also compared these parameters with those in a
      group of patients receiving simvastatin therapy. Concentrations of lipid
      hydroperoxides (LOOHs) and malondialdehyde, the total antioxidant capacity
      (assessed by ferric reducing antioxidant power assay), concentration of thiol (
      SH) groups, and ceruloplasmin activity were determined spectrophotometrically in
      PAD patients treated surgically (Group I) or pharmacologically (Group II). The
      patients before surgical treatment had significantly higher concentrations of
      malondialdehyde but lower ceruloplasmin activity than those observed in Group II,
      treated with simvastatin. No significant differences before surgery in ferric
      reducing antioxidant power or thiol concentrations were found between the two
      groups. However, in Group I, both ferric reducing antioxidant power and thiol
      group concentrations decreased 3-5 days postoperatively, and ceruloplasmin
      activity increased 7-10 days after surgical treatment. The presented results
      demonstrate diverse oxidative stress responses to surgical treatment and confirm
      the beneficial effects of statin therapy in PAD. 

PMID- 24302810
TI  - An MLP classifier for prediction of HBV-induced liver cirrhosis using routinely
      available clinical parameters.
AB  - BACKGROUND: Liver cirrhosis (LC) is the final stage of most of chronic liver
      diseases and is almost caused by chronic hepatitis B (CHB) in China. Liver biopsy
      is the reference method for the evaluation of liver cirrhosis. However, it is an
      invasive procedure with inherent risk. The aim of this study was to construct a
      new classifier based on the routine clinical markers for the prediction of HBV
      induced LC. SUBJECTS AND METHODS: We collected routine clinical parameters from
      124 LC patients with CHB and 115 with CHB. Training set (n = 120) and test set (n
      = 119) were built for model construction and evaluation, respectively. RESULTS:
      We describe a new classifier, MLP, for prediction of LC with CHB. MLP was built
      with seven routinely available clinical parameters, including age, ALT, AST, PT,
      PLT, HGB, and RDW. With optimal cutoff, we obtained a sensitivity of 95.2%, a
      specificity of 84.2%, and an overall accuracy of 89.9% on an independent test
      set, which were superior to those of FIB-4 and APRI. CONCLUSIONS: Our study
      suggests that the MLP classifier can be implemented for discriminating LC and non
      LC cohorts by using machine learning method based on the routine available
      clinical parameters. It could be used for clinical practice in HBV-induced LC
      assessment.

PMID- 24302811
TI  - Sex-specific genomic biomarkers for individualized treatment of life-threatening
      diseases.
AB  - Numerous studies have demonstrated sex differences in drug reactions to the same
      drug treatment, steering away from the traditional view of one-size-fits-all
      medicine. A premise of this study is that the sex of a patient influences
      difference in disease characteristics and risk factors. In this study, we intend
      to exploit and to obtain better sex-specific biomarkers from gene-expression
      data. We propose a procedure to isolate a set of important genes as sex-specific
      genomic biomarkers, which may enable more effective patient treatment. A set of
      sex-specific genes is obtained by a variable importance ranking using a
      combination of cross-validation methods. The proposed procedure is applied to
      three gene-expression datasets. 

PMID- 24302812
TI  - High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine
      MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in
      Border Collie dogs.
AB  - A single nucleotide substitution (c.-6-180T>G) associated with resistance to
      phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border
      Collies with idiopathic epilepsy. In the present study, a PCR-restriction
      fragment length polymorphism assay was developed for genotyping this mutation,
      and a genotyping survey was carried out in a population of 472 Border Collies in
      Japan to determine the current allele frequency. The survey demonstrated the
      frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to
      be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the
      mutant G allele is extremely high (24.9%) in Border Collies. The results suggest
      that this high mutation frequency of the mutation is likely to cause a high
      prevalence of phenobarbital-resistant epilepsy in Border Collies. 

PMID- 24302813
TI  - Electrocardiographic Screening of Emphysema: Lead aVL or Leads III and I?

PMID- 24302814
TI  - Plasmacytoid dendritic cell response to CpG ODN correlates with CXCL16 expression
      and is inhibited by ox-LDL.
AB  - Structurally distinct classes of synthetic CpG oligonucleotides (ODN)
      differentially activate human immune cells. K-type ODN trigger plasmacytoid
      dendritic cells (pDCs) to differentiate and produce TNF alpha . In contrast, D
      type ODN stimulate large amounts of IFN alpha secretion from pDCs. The cell
      surface receptor CXCL16 was previously shown to influence the nature and
      specificity of CpG ODN-induced immune activation. Here, we evaluated the
      expression and function of CXCL16 on pDC from healthy volunteers. We report that
      increased CXCL16 expression correlated with enhanced in vitro response
      exclusively to D-type CpG ODN. Conversely, enzymatic digestion of the receptor
      resulted in a decrease in IFN alpha production. Moreover, ox-LDL presence
      significantly inhibited D-ODN mediated IFN alpha production by pDCs. Coculture of
      enriched pDCs with the CXCR6 expressing Jurkat T cells decreased the activation
      threshold of these cells responding to D-ODN, suggesting that CXCL16/CXCR6
      interaction may play an important role in modifying the response of pDCs to
      environmental danger signals. 

PMID- 24302817
TI  - Conjugate pneumococcal vaccines: need and choice in India.

PMID- 24302815
TI  - Cytokines and chemokines as regulators of skeletal muscle inflammation:
      presenting the case of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1
      in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is
      an important facet of disease pathophysiology and is strongly associated with
      disease severity in the individual patient. In the chronic inflammation that
      characterizes Duchenne muscle, cytokines and chemokines are considered essential
      activators and recruiters of inflammatory cells. In addition, they provide
      potential beneficiary effects on muscle fiber damage control and tissue
      regeneration. In this review, current knowledge of cytokine and chemokine
      expression in Duchenne muscular dystrophy and its relevant animal disease models
      is listed, and implications for future therapeutic avenues are discussed. 

PMID- 24302816
TI  - HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial
      fibroblasts via p38 MAPK and NF-kappaB signaling pathways.
AB  - Synovial fibroblasts (SF) play a central role in the inflammatory and destructive
      process in rheumatoid arthritis (RA). High-mobility group box chromosomal protein
      1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes
      in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS
      (HMGB1-LPS) significantly facilitated SF proliferation. HMGB1 alone failed to
      induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS
      induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels.
      HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation
      endproducts (RAGE) expression on the surface of SF. Both blockers of TLR4 and
      RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the
      production of IL-6 and MMPs, but blocking antibodies to TLR2 failed. HMGB1-LPS
      synergistically increased intracellular levels of phosphorylated p38 and
      phosphorylated I kappa B. Furthermore, both NF- kappa B inhibitor Bay11-7085 and
      p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6
      and MMPs induced by HMGB1-LPS. In conclusion, HMGB1 acts in synergy with LPS to
      upregulate TLR4 and RAGE expression on the surface of SF in RA and then to
      augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF
      kappaB activation.

PMID- 24302818
TI  - Increasing fruit and vegetable consumption: challenges and opportunities.

PMID- 24302820
TI  - A study to assess the emotional disorders with special reference to stress of
      medical students of agartala government medical college and govinda ballabh pant
      hospital.
AB  - BACKGROUND: Stress is very common psychological phenomena where medical students
      faced in day to day activities. Epidemiological studies have asserted that about
      70-80% of the diseases may be related to stress. Research related to this stress
      especially among medical students is essential, considering their learning, role
      and responsibilities as a future physician and health intervention programs.
      OBJECTIVES: To estimate the prevalence of stress and identify stressors among
      medical students. MATERIALS AND METHODS: A Cross-sectional study was carried out
      among undergraduate medical students and self administered GHQ-12 and stressor
      questionnaire were used to collect information regarding stress. Binary logistic
      regression analysis was performed to calculate odds ratio (OR). RESULTS:
      Prevalence of stress was 94.52% and more common among females. 33.56% students
      felt constantly under strain and 25.34% had loss of sleep over worry. Majority of
      the students of all semesters had stress (P > 0.05) and stressors viz.
      'competition for marks' (P = 0.005), 'frequent examination' (P = 0.001),
      'difficulty in finding time for recreation' (P = 0.014) and 'being away from
      home' (P = 0.027) were predominantly experienced by the 1(st) year medical
      students. Multiple logistic regression analysis revealed the causal effect of
      main parameter on the GHQ caseness and students who found difficulties in
      following teaching language among the caseness had 81.59% higher chance of
      developing stress (OR = 8.159, CI = 1.228-54.213). CONCLUSION: The stress
      experience was more common due to academics and seen among all year of medical
      students. Strategy development for eliminating stressors is necessary for
      promoting healthy life.

PMID- 24302819
TI  - Burden of corneal blindness in India.

PMID- 24302821
TI  - Effect of prenatal exposure to kitchen fuel on birth weight.
AB  - BACKGROUND: Maternal exposure to kitchen fuel smoke may lead to impaired fetal
      growth. OBJECTIVE: To study the effect of exposure to various kitchen fuels on
      birth weight. METHODOLOGY:  STUDY TYPE: Retrospective analytical. STUDY SETTING:
      Hospital based. STUDY SUBJECTS: Mothers and their newborns. INCLUSION CRITERIA:
      Mothers registered in first trimester with minimum 3 visits, non-anemic, full
      term, and singleton delivery. EXCLUSION CRITERIA: History of Pregnancy Induced
      Hypertension (PIH), Diabetes Mellitus (DM), tobacco chewers or mishri users.
      SAMPLE SIZE: 328 mothers and their new-borne. STUDY PERIOD: Six months. Study
      tools: Chi-square, Z-test, ANOVA, and binary logistic regression. RESULTS: Effect
      of confounders on birth weight was tested and found to be non-significant. Mean
      +/- SD of birth weight was 2.669 +/- 0.442 in Liquid Petroleium Gas (LPG) users
      (n = 178), 2.465 +/- 0.465 in wood users (n = 94), 2.557 +/- 0.603 in LPG + wood
      users (n = 27) and 2.617 +/- 0.470 in kerosene users (n = 29). Infants born to
      wood users had lowest birth weight and averagely 204 g lighter than LPG users (F
      = 4.056, P < 0.01). Percentage of newborns with low birth weight (LBW) in wood
      users was 44.68% which was significantly higher than in LPG users (24.16%), LPG +
      wood users (40.74%) and in kerosene users (34.48%) (Chi-square = 12.926, P <
      0.01). As duration of exposure to wood fuel increases there is significant
      decline in birth weight (F = 3.825, P < 0.05). By using logistic regression type
      of fuel is only best predictor. CONCLUSION: Cooking with wood fuel is a
      significant risk-factor for LBW, which is modifiable.

PMID- 24302822
TI  - Health seeking behavior in karnataka: does micro-health insurance matter?
AB  - BACKGROUND: Health seeking behaviour in the event of illness is influenced by the
      availability of good health care facilities and health care financing mechanisms.
      Micro health insurance not only promotes formal health care utilization at
      private providers but also reduces the cost of care by providing the insurance
      coverage. OBJECTIVES: This paper explores the impact of Sampoorna Suraksha
      Programme, a micro health insurance scheme on the health seeking behaviour of
      households during illness in Karnataka, India. MATERIALS AND METHODS: The study
      was conducted in three randomly selected districts in Karnataka, India in the
      first half of the year 2011. The hypothesis was tested using binary logistic
      regression analysis on the data collected from randomly selected 1146 households
      consisting of 4961 individuals. RESULTS: Insured individuals were seeking care at
      private hospitals than public hospitals due to the reduction in financial
      barrier. Moreover, equity in health seeking behaviour among insured individuals
      was observed. CONCLUSION: Our finding does represent a desirable result for
      health policy makers and micro finance institutions to advocate for the inclusion
      of health insurance in their portfolio, at least from the HSB perspective.

PMID- 24302823
TI  - Study of rogi kalyan samitis in strengthening health systems under national rural
      health mission, district pune, maharashtra.
AB  - BACKGROUND: With objective of health systems strengthening, as visualized under
      National Rural Health Mission (NRHM); one key strategic intervention is up
      gradation of health service delivery facilities so as to provide sustainable
      quality care with accountability and people's participation, which required the
      development of a proper management structure called Rogi Kalyan Samitis (RKS). It
      is the State's attempt to make health everyone's business by de-mystifying health
      care delivery at district and sub-district levels with reference to facility
      based health-care delivery by encouraging citizen's participation in management
      bodies. OBJECTIVE: The study was an attempt to define 'functional Health Systems'
      with a focus on strategic issues concerning RKS operations. MATERIALS AND
      METHODS: A mixed-method, multi-site, collective case study approach was adopted.
      In-depth interviews of key-stakeholders were conducted. Qualitative data were
      analyzed thematically and coded inductively. RESULTS: RKS is yet to bring out
      quality component to the health services being provided through facilities. This
      can be attributed to structural and managerial weakness in the system; however,
      certainly NRHM has been consistent in creating a road-map for benefitting local
      community and their participation through RKS. CONCLUSION: The progress of the
      RKS can further be enhanced by giving due priority to critical areas.
      Furthermore, the results emphasize an urgent need for devising strategies and
      actions to overcome significant systemic constraints as highlighted in the
      present study.

PMID- 24302824
TI  - A Study on the Role of Mobile Phone Communication in Tuberculosis DOTS Treatment.
AB  - BACKGROUND: Every year, a lot of Tuberculosis (TB) patients undergo Directly
      Observed Treatment Short-course (DOTS) in Salem city, one of the high TB
      districts in South India. Mobile phone usage among these patients and health
      workers is common. Mobile phone communication has a great potential in TB
      treatment. OBJECTIVES: To analyze the mobile phone usage and its effectiveness in
      TB DOTS treatment. MATERIALS AND METHODS: A cross-sectional survey with 150 TB
      patients was followed by a focus group discussion with treatment supervisors,
      DOTS providers, and health workers. RESULTS: Majority of patients use mobile
      phones to make calls to health workers to clarify their doubts on side effects,
      food, and symptoms of the disease. TB treatment supervisors effectively use
      mobile phones to counsel patients to adhere to the treatment regimen. Patients
      see mobile phones as a useful communication tool in TB treatment though they
      prefer direct interpersonal communication with health workers. Though the mobile
      ownership is 68% among the TB patients, many of them are not able to send text
      messages or read messages in English. CONCLUSION: Mobile phone possession and
      usage is high among the patients. Patients need to be trained to use mobile phone
      features such as alarm, voice mail, and interactive voice response. Incentives
      like free talk time and short message service (SMS) will encourage patients to
      communicate frequently with health workers, thereby, increasing the chances of
      better adherence to DOTS. SMS could be made available in the regional languages.

PMID- 24302825
TI  - Community based maternal and child health nutrition project, uttar pradesh: an
      innovative strategy focusing on "at risk" families.
AB  - RESEARCH QUESTION: Use of community based volunteers, frequently reaching and
      counseling a selected group of prioritized families, can make a substantial
      difference in improving maternal and child care practices and in reducing child
      undernutrition. SETTING: Program Rural Uttar Pradesh, India. STUDY DESIGN: A
      comparison of baseline and endline surveys following 4 years of community based
      project intervention. PARTICIPANTS: "At risk" undernutrition families comprising
      mothers of under twos, newlyweds, and severely undernourished children below 6
      years. INTERVENTION: Mapping and counseling of "at risk" families. Measuring
      impact on maternal-child care practices, underweight status. RESULTS: Trained
      community mobilizers identified and counseled selected "at risk" families.
      Following 4 years of implementation in 907 villages of 8 blocks of four
      districts, significant improvement was noted in practices of early initiation of
      breastfeeding, feeding colostrum, timely introduction of complementary feeding,
      and washing the hands after defecation. Percentage of mothers exclusively
      breastfeeding at 6 months was only 2.1% with 78% receiving prelacteal feeds. A
      small increase in normal and mild malnutrition and a significant reduction of 43%
      in severe malnutrition was noted. CONCLUSION: Frequently counseling by accredited
      social health activists by focusing on selected defined "at risk" families of
      under twos and those with severe malnourished children could result in increasing
      acceptability of correct child health, feeding, and care practices and in
      contributing to improving nutritional status scenario.

PMID- 24302826
TI  - Investigation of a cholera outbreak in a tea garden of sivasagar district of
      assam.
AB  - BACKGROUND: In late May 2012, Bagjan division of Borbam tea estate, of Sivasagar
      district of Assam was affected by an outbreak of acute watery diarrhea,
      subsequently confirmed as Vibrio cholerae O1. OBJECTIVES: Our objective is to
      investigate and control the acute diarrheal disease outbreak in Sivasagar
      district of Assam. MATERIALS AND METHODS: A physician-epidemiologist-led team did
      rapid outbreak investigation to confirm the outbreak and instituted treatment and
      control measures. Quantitative data collection was done using standard schedule
      and qualitative data by using key informant interview schedule. RESULTS: Spot
      mapping of cases was done along the garden residential lines. About 120 suspected
      cases were line listed; with 1:1.23 male: female ratio. Ages ranged from 3 to 70
      years (median - 40.5 years). Attack rate was 4.79% with one death; case fatality
      rate was 0.83%. Open air defecation was practiced by 94.6%. Rectal swabs were
      positive for V. cholerae O1 (Ogawa). All the piped water samples were class IV
      unsatisfactory for domestic use. CONCLUSIONS: There is a need to improve water
      and sanitation facility in the tea garden lines along with implementation of a
      strengthened disease surveillance system through integrated disease surveillance
      project covering all tea estates.

PMID- 24302827
TI  - Breastfeeding week celebrations in rural puducherry.

PMID- 24302828
TI  - Reply to: Dilemmas in Immunization?

PMID- 24302829
TI  - Factors associated with attitudes of rural women toward cervical cancer
      screening.

PMID- 24302830
TI  - Increase in hemoglobin among the mothers at different levels of hemoglobin.

PMID- 24302831
TI  - Nucleic acid amplification: Alternative methods of polymerase chain reaction.
AB  - Nucleic acid amplification is a valuable molecular tool not only in basic
      research but also in application oriented fields, such as clinical medicine
      development, infectious diseases diagnosis, gene cloning and industrial quality
      control. A comperehensive review of the literature on the principles,
      applications, challenges and prospects of different alternative methods of
      polymerase chain reaction (PCR) was performed. PCR was the first nucleic acid
      amplification method. With the advancement of research, a no of alternative
      nucleic acid amplification methods has been developed such as loop mediated
      isothermal amplification, nucleic acid sequence based amplification, strand
      displacement amplification, multiple displacement amplification. Most of the
      alternative methods are isothermal obviating the need for thermal cyclers. Though
      principles of most of the alternate methods are relatively complex than that of
      PCR, they offer better applicability and sensitivity in cases where PCR has
      limitations. Most of the alternate methods still have to prove themselves through
      extensive validation studies and are not available in commercial form; they pose
      the potentiality to be used as replacements of PCR. Continuous research is going
      on in different parts of the world to make these methods viable technically and
      economically. 

PMID- 24302832
TI  - Effects of moxonidine on sympathetic nervous system activity: An update on
      metabolism, cardio, and other target-organ protection.
AB  - Moxonidine is the newest, second-generation, centrally acting antihypertensive
      agent. It has selective agonist activity at imidazoline I1 receptors and less
      adverse effects than the other centrally acting drugs. This fact authorizes the
      frequent use of moxonidine in clinical practice, as monotherapy or in combination
      with other antihypertensive agents. Also, moxonidine has beneficial effects in
      obese and metabolic syndrome and in target-organs, such as heart and kidneys. 

PMID- 24302833
TI  - Bioanalytical method development and validation of alimemazine in human plasma by
      LC-MS/MS and its application in bioequivalence studies.
AB  - BACKGROUND: The use of anti-histaminic agents has been increased significantly
      from last decades and till now no method is available for quantitation of ALZ in
      human plasma which can be applied in a bioequivalence study using LC-MS/MS.
      OBJECTIVE: The present study is concerned with the development and validation of
      ALZ in human plasma by high performance liquid chromatography tandem mass
      spectrometry (HPLC-MS/MS). MATERIALS AND METHODS: Sample preparation involved the
      extraction with liquid-liquid extraction method by using ethyl acetate as an
      organic solvent. Chromatographic separation was performed on Atlantis(r) T3 5 MUm
      4.6 mm * 150 mm column with the mobile phase consisting of acetonitrile: (10 mm
      ammonium formate buffer: Formic acid: 99.9:00.1 v/v) 50:50 v/v. The interface
      used with the application programming interface 4000 LC-MS/MS was a turbo ion
      spray in which positive ions were measured in multiple reaction monitoring mode.
      The precursor to product ions transition of m/z 299.30 -> 100.20 amu and 305.30 
      > 106.30 amu were used for ALZ and ALZ D6 respectively. RESULTS: The method was
      validated over the concentration range of 20.013-10006.551 pg/mL. The mean
      percent recovery of ALZ was found 77.771% with a precision of 7.71% and the lower
      limit of quantification was 20.013 pg/mL. The intra- and inter-day precision of
      the method at three concentrations was 0.98-4.50% and 1.57-5.72% while the intra-
      and inter-day % accuracy was 99.02-93.82% and 101.78-106.96%. Stability of
      compounds was established in a series of stability studies. The application of
      this method was demonstrated in the bioequivalence study and was found suitable
      in a study of sample size as big as 30 enrolled volunteers. CONCLUSION: For the
      very first time, a sensitive, selective and robust Liquid Chromatography- Mass
      Spectrometry method for the determination of alimemazine (ALZ) in human plasma
      has been developed and validated using ALZ D6 as an internal standard.

PMID- 24302834
TI  - Antibacterial activity of resin rich plant extracts.
AB  - BACKGROUND: The in vitro antibacterial activity of resin rich methanolic extracts
      (RRMEs) of Commiphora myrrha, Operculina turpethum, and Pinus roxburghii.
      MATERIALS AND METHODS: Different concentration were studied by agar-well
      diffusion method against Gram-positive (Staphylococcus aureus, Bacillus subtilis,
      Micrococcus luteus, Enterococcus faecalis) and Gram-negative bacterial strains
      (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella
      dysenteriae). RESULTS: Among all the bacterial strains tested, E. faecalis was
      most sensitive and S. typhi was resistant to C. myrrha and P. roxburghii. The
      extracts of O. turpethum were active against all tested strains in which B.
      subtilis and S. aureus were the most sensitive. CONCLUSION: This suggested that
      the antibacterial activity of RRMEs of O. turpethum was more than C. myrrha and
      P. roxburghii. This probably explains the potential of these plants against a
      number of infections caused by bacterial strains tested.

PMID- 24302835
TI  - Mitigation of starch-induced postprandial glycemic spikes in rats by antioxidants
      rich extract of Cicer arietinum Linn. seeds and sprouts.
AB  - INTRODUCTION: Consumption of highly processed calories dense diet leads abrupt
      increase in postprandial blood glucose level, which in turn induces immediate
      oxidative stress. Postprandial hyperglycemia (PPHG) and resultant oxidative
      stress is one of the earliest detectable abnormalities in diabetes prone
      individuals, independent risk factor for development of cardiovascular disorders
      (CVD), a major pathophysiological link between diabetes and CVD and an important
      contributing factor in atherogenesis even in non-diabetic individuals. Therefore,
      dietary supplements mitigating PPHG spikes along with potent antioxidant
      activities may help decrease development of PPHG and oxidative stress induced
      pathogenesis. OBJECTIVES: The study evaluated free radicals scavenging,
      antioxidant properties and intestinal alpha-glucosidase inhibitory activity in
      methanol extract of two varieties of Cicer arietinum Linn viz. Bengal gram and
      Kabuli chana and green gram (Vigna radiata Linn. Wilczek) raw grains and their
      sprouts and studied their influence on starch-induced postprandial glycemic
      excursion in rats. MATERIALS AND METHODS: Healthy grains were procured from local
      markets. Free radicals scavenging antioxidant and glucose-induced hemoglobin (Hb)
      glycation inhibition activities were analyzed using standard in vitro procedures.
      In vitro antihyperglycemic activity was evaluated by assessing rat intestinal
      alpha-glucosidase inhibitory activity. Influence on starch-induced postprandial
      glycemic excursion in rats was studied by pre-treatment of rats with extracts.
      RESULTS: Compared with raw seeds increase in total polyphenol and flavonoids
      concentration in green gram sprouts and Kabuli chana sprouts (KCs) were observed.
      Total protein concentrations in sprouts did not differ from non-sprouted grains.
      2,2'- Azinobis (3-ethyl benzthiazoline-6-sulphonic acid) cation scavenging
      activity was more than twice in Bengal gram sprouts of (BGs) and KCs than their
      raw seeds. 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide scavenging, nitro
      blue tetrazolium reducing and glucose-induced Hb-glycation inhibitory activity
      did not differ from non-sprouted raw grains. Increase in rat intestinal alpha
      glucosidase inhibitory activity was observed in BGs and KCs. BGs significantly
      mitigated 1(st) 30 min starch-induced postprandial glycemic excursions and
      reduced 2 h postprandial glycemic load. CONCLUSION: Sprouting leads dynamic
      changes in free radicals scavenging potentials and antioxidant activities in
      grains. Consumption of seeds as well as BGs before the starch-rich meal can
      significantly mitigate 1(st) 30 min postprandial glycemic excursion and reduce 2
      h postprandial glycemic burden.

PMID- 24302836
TI  - Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine
      derivatives.
AB  - INTRODUCTION: A practical synthesis of pyrimidinone would be very helpful for
      chemists because pyrimidinone is found in many bioactive natural products and
      exhibits a wide range of biological properties. The biological significance of
      pyrimidine derivatives has led us to the synthesis of substituted pyrimidine.
      MATERIALS AND METHODS: With the aim of developing potential antimicrobials, new
      series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine derivatives namely 2-(5-cyano-6
      oxo-4-substituted (aryl)-1,6-dihydropyrimidin-2-ylthio)-N-substituted (phenyl)
      acetamide (C1-C41) were synthesized and characterized by Fourier transform
      infrared spectroscopy (FTIR), mass analysis, and proton nuclear magnetic
      resonance ((1)H NMR). All the compounds were screened for their antifungal
      activity against Candida albicans (MTCC, 227). RESULTS AND DISCUSSION:
      Quantitative structure activity relationship (QSAR) studies of a series of 1,6
      dihydro-pyrimidine were carried out to study various structural requirements for
      fungal inhibition. Various lipophilic, electronic, geometric, and spatial
      descriptors were correlated with antifungal activity using genetic function
      approximation. Developed models were found predictive as indicated by their
      square of predictive regression values (r(2pred)) and their internal and external
      cross-validation. Study reveals that CHI_3_C, Molecular_SurfaceArea, and
      Jurs_DPSA_1 contributed significantly to the activity along with some electronic,
      geometric, and quantum mechanical descriptors. CONCLUSION: A careful analysis of
      the antifungal activity data of synthesized compounds revealed that electron
      withdrawing substitution on N-phenyl acetamide ring of 1,6-dihydropyrimidine
      moiety possess good activity.

PMID- 24302837
TI  - Enhanced tumor uptake, biodistribution and pharmacokinetics of etoposide loaded
      nanoparticles in Dalton's lymphoma tumor bearing mice.
AB  - BACKGROUND: Nanotechnology plays a remarkable role in the field of the treatment
      of Lymphomas associated with tumor. OBJECTIVE: The purpose of this study is to
      determine and to compare the tumor uptake, biodistribution and pharmacokinetics
      of radiolabeled etoposide and etoposide loaded nanoparticles in Dalton's Lymphoma
      tumor bearing mice and healthy mice. MATERIALS AND METHODS: Etoposide loaded
      nanoparticles were prepared by nanoprecipitation technique using the poly (lactic
      co-glycolic) acid (PLGA) in the presence of Pluronic F 68 (F 68) as a stabilizer
      and characterized by particle size analyzer, zeta potential and transmission
      electron microscope. Etoposide and etoposide loaded nanoparticles were labeled
      with Technetium-99m (Tc-99m) by the direct method and various quality control
      tests were carried out. The labeling parameters like labeling efficiency,
      stability, etc., were optimized to get high labeling efficiency as well as
      stability of the labeled formulations. Tc-99m labeled formulations were
      administered intravenously in Balb C mice and their biodistribution and
      pharmacokinetics were determined. RESULTS: Mean size of the etoposide loaded PLGA
      nanoparticles was found to be 105.1 nm. The concentration of both free etoposide
      and nanoparticles increased with time and showed higher tumor concentrations of
      both free etoposide and nanoparticles increased with time and showed higher
      retention, indicating their applicability in effective and prolonged tumor
      therapy. Nuclear scintigraphic images confirm the presence of labeled complexes
      at the site of tumor for 24 h at higher concentration than in the normal muscles.
      CONCLUSION: This study indicated higher tumor affinity and targeting properties
      of etoposide loaded nanoparticles than free etoposide.

PMID- 24302838
TI  - A novel validated stability indicating high performance liquid chromatographic
      method for estimation of degradation behavior of ciprofloxacin and tinidazole in
      solid oral dosage.
AB  - OBJECTIVE: The objective of current investigation was to study the degradation
      behavior of Ciprofloxacin and Tinidazole. The study was performed as per
      International Conference on Harmonization recommended stress condition. A novel
      stability-indicating reverse phase HPLC method was developed for the
      determination of Ciprofloxacin and Tinidazole purity in the presence of its
      impurities and forced degradation products. This method is also capable to
      separate placebo peaks as well in pharmaceutical dosage forms. The solid oral
      dosage form was subjected to the stress conditions such as oxidative, acid, base
      hydrolysis, heat and photolytic degradation. MATERIALS AND METHODS: The method
      was developed using Waters symmetry shield, Reverse Phase (RP) C18, 250mm x
      4.6mm, 5MU as a stationary phase. The mobile phase containing a gradient mixture
      of solvent A and B. 10mM phosphate buffer, adjusted pH 3.0 with phosphoric acid
      was used as a buffer. Buffer pH 3.0 was used as solvent A and buffer pH 3.0:
      Acetonitrile in the ratio of 20: 80 v/v were used as solvent B. The eluted
      compounds were monitored 278 nm (Ciprofloxacin), 317 nm (Tinidazole). The run
      time was 50 minute. RESULTS: In the precision study the % RSD for the result of
      Ciprofloxacin, Tinidazole and its impurities was below 10%. The method was linear
      with the correlation coefficient greater than 0.997. The percentage recoveries
      were calculated and observed from 93.0% to 106.7%. The peak purity of
      Ciprofloxacin, Tinidazole peak had not shown any flag, thus proved the stability
      indicating power of the method. CONCLUSION: The developed method was validated as
      per ICH guidelines with respect to specificity, linearity, limit of detection,
      limit of quantification, accuracy, precision and robustness.

PMID- 24302839
TI  - Effect of aqueous extract of Rheum ribes on cisplatin-induced nephrotoxicity in
      rat.
AB  - OBJECTIVE: The purpose of the present study was to examine whether Rheum ribes
      extract prevents cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: THE
      ANIMALS WERE DIVIDED INTO THREE GROUPS: Group A considered as control group,
      group B were treated with cisplatin (3 mg/kg B.W. for 3 alternative days), and
      group C further to cisplatin received the aqueous extract of Rheum ribes (150
      mg/rat). RESULTS: Blood urea nitrogen (BUN) level increased in group B on days 14
      and 42 compared to day 0 (P < 0.001); it was also increased in group B vs. group
      A on day 14 (P < 0.001). Rheum ribes extract decreased the serum BUN level on day
      14 compared to group B (P < 0.001). Serum creatinine level in group B had a
      similar profile as serum BUN level but Rheum ribes had no effect on blood
      creatinine level. Serum cholesterol level was increased in group B on days 14 and
      42 compared to day 0 (P < 0.001). Also, cholesterol level was significantly
      increased in group B when compared to group A on day 14 (P < 0.001). Rheum ribes
      decreased the blood cholesterol level on day 42 in comparison to group B (P <
      0.001). Serum glucose level was increased in group B on days 14 and 42 vs. day 0
      (P < 0.001). Also, glucose level was significantly increased in group B when
      compared to group A on day 42 (P < 0.001). Rheum ribes increased the serum
      glucose level on days 14 and 42 compared to day 0 (P < 0.05). Histology of
      kidneys exposed to cisplatin showed renal injury, but Rheum ribes had no effect
      on the kidney architecture. CONCLUSION: Cisplatin-induced nephrotoxicity was
      confirmed in our study. Although Rheum ribes had some effects on biochemical
      parameters; its effect on renal histology in injured kidney was insignificant.

PMID- 24302840
TI  - Determination of galantamine hydrobromide in bulk drug and pharmaceutical dosage
      form by spectrofluorimetry.
AB  - AIM: To develop a simple, accurate, sensitive, rapid and precise method for the
      determination of galantamine hydrobromide in bulk drug and pharmaceutical dosage
      form. MATERIAL AND METHODS: The method employs wavelength detection and
      determination of galantamine hydrobromide at excitation wavelength 282 nm and
      emission wavelength 607 nm in a solution of simple distilled water. RESULT AND
      CONCLUSION: The method was found to be linear in the range of 2-14 MUg/ml having
      r (2) = 0.9999. The mean accuracy was found to be 98.12% to 99.67%. The intraday
      and interday precision was found to be 0.18-0.35% and 0.13-0.46%, respectively.
      The limit of detection was found to be 0.29 MUg/ml. The limit of quantification
      was found to be 0.89 MUg/ml. The method was successfully applied for the
      determination of galantamine hydrobromide in bulk drug as well as pharmaceutical
      dosage form.

PMID- 24302841
TI  - Design and development of cefdinir niosomes for oral delivery.
AB  - OBJECTIVE: The aim of the present study was to develop nonionic surfactant based
      vesicles (niosomes) to improve poor and variable oral bioavailability of
      cefdinir. MATERIALS AND METHODS: Cefdinir niosomes were formulated by sonication
      method using varying concentration of surfactant (span 60), with and without soya
      lecithin, but the cholesterol ratio was kept constant in all the formulations.
      The influence of formulation variables such as surfactant concentration, soya
      lecithin presence or absence were optimized for size and entrapment efficiency.
      Drug excipient interaction studies were performed using FTIR, indicating
      compatibility of excipients with drug. RESULTS: The highest entrapment efficiency
      (74.56%) was observed when span 60, cefdinir, cholesterol and soya lecithin were
      used in the ratio of 5:1:1:1. The zeta sizer of the niosomal formulations showed
      the size range between 190 nm-1140 nm. The photomicrography showed round shape of
      vesicles and further nano size of niosomes was confirmed by scanning and
      transmission electron microscopy. The optimized niosomal formulations (F11 and
      F6) exhibited sustained in-vitro release of 94.91% and 94.07% respectively upto
      12 h. The ex-vivo permeation studies of optimized formulation revealed that the
      niosomal dispersion improved cefdinir permeability across goat intestinal
      membrane as compared to plain drug solution and marketed suspension (Adcef(r)).
      Antimicrobial activity studies revealed that the niosomes potentiated
      bacteriostatic activity of cefdinir as compared to Adcef(r). CONCLUSION: The
      niosomal formulation could be one of the promising delivery system for cefdinir
      with improved oral bioavailability and controlled drug release profile.

PMID- 24302842
TI  - Job satisfaction among Indian pharmacists.

PMID- 24302843
TI  - Osteogenic action of anti-diabetic drug metformin in periodontal disease.

PMID- 24302844
TI  - Isospora spp. in chronic diarrhea: A case report.

PMID- 24302845
TI  - Aspirin intake: Can be a confounding factor in clinical trial for periodontal
      disease.

PMID- 24302846
TI  - Platelet concentrates: Regenerating the lost tissues.

PMID- 24302847
TI  - A well-substantiated report is as vital to science as is a well-designed study.

PMID- 24302848
TI  - Response from editor.

PMID- 24302849
TI  - Models and Strategies for Factor Mixture Analysis: An Example Concerning the
      Structure Underlying Psychological Disorders.
AB  - The factor mixture model (FMM) uses a hybrid of both categorical and continuous
      latent variables. The FMM is a good model for the underlying structure of
      psychopathology because the use of both categorical and continuous latent
      variables allows the structure to be simultaneously categorical and dimensional.
      This is useful because both diagnostic class membership and the range of severity
      within and across diagnostic classes can be modeled concurrently. While the
      conceptualization of the FMM has been explained in the literature, the use of the
      FMM is still not prevalent. One reason is that there is little research about how
      such models should be applied in practice and, once a well fitting model is
      obtained, how it should be interpreted. In this paper, the FMM will be explored
      by studying a real data example on conduct disorder. By exploring this example,
      this paper aims to explain the different formulations of the FMM, the various
      steps in building a FMM, as well as how to decide between a FMM and alternative
      models.

PMID- 24302850
TI  - Computational Fluid Dynamics Simulation of Flows in an Oxidation Ditch Driven by
      a New Surface Aerator.
AB  - In this article, we present a newly designed inverse umbrella surface aerator,
      and tested its performance in driving flow of an oxidation ditch. Results show
      that it has a better performance in driving the oxidation ditch than the original
      one with higher average velocity and more uniform flow field. We also present a
      computational fluid dynamics model for predicting the flow field in an oxidation
      ditch driven by a surface aerator. The improved momentum source term approach to
      simulate the flow field of the oxidation ditch driven by an inverse umbrella
      surface aerator was developed and validated through experiments. Four kinds of
      turbulent models were investigated with the approach, including the standard k-E
      model, RNG k-E model, realizable k-E model, and Reynolds stress model, and the
      predicted data were compared with those calculated with the multiple rotating
      reference frame approach (MRF) and sliding mesh approach (SM). Results of the
      momentum source term approach are in good agreement with the experimental data,
      and its prediction accuracy is better than MRF, close to SM. It is also found
      that the momentum source term approach has lower computational expenses, is
      simpler to preprocess, and is easier to use.

PMID- 24302851
TI  - Biostimulation Reveals Functional Redundancy of Anthracene-Degrading Bacteria in
      Polycyclic Aromatic Hydrocarbon-Contaminated Soil.
AB  - Stable-isotope probing was previously used to identify bacterial anthracene
      degraders in untreated soil from a former manufactured gas plant site. However,
      subsequent pyrosequence analyses of total bacterial communities and
      quantification of 16S rRNA genes indicated that relative abundances of the
      predominant anthracene-degrading bacteria (designated Anthracene Group 1)
      diminished as a result of biological treatment conditions in lab-scale, aerobic
      bioreactors. This study identified Alphaproteobacterial anthracene-degrading
      bacteria in bioreactor-treated soil which were dissimilar to those previously
      identified. The largest group of sequences was from the Alterythrobacter genus
      while other groups of sequences were associated with bacteria within the order
      Rhizobiales and the genus Bradyrhizobium. Conditions in the bioreactor enriched
      for organisms capable of degrading anthracene which were not the same as those
      identified as dominant degraders in the untreated soil. Further, these data
      suggest that identification of polycyclic aromatic hydrocarbon-degrading bacteria
      in contaminated but untreated soil may be a poor indicator of the most active
      degraders during biological treatment.

PMID- 24302853
TI  - Young Infants Match Facial and Vocal Emotional Expressions of Other Infants.
AB  - Research has demonstrated that infants recognize emotional expressions of adults
      in the first half-year of life. We extended this research to a new domain, infant
      perception of the expressions of other infants. In an intermodal matching
      procedure, 3.5- and 5-month-old infants heard a series of infant vocal
      expressions (positive and negative affect) along with side-by-side dynamic videos
      in which one infant conveyed positive facial affect and another infant conveyed
      negative facial affect. Results demonstrated that 5-month-olds matched the vocal
      expressions with the affectively congruent facial expressions, whereas 3.5-month
      olds showed no evidence of matching. These findings indicate that by 5 months of
      age, infants detect, discriminate, and match the facial and vocal affective
      displays of other infants. Further, because the facial and vocal expressions were
      portrayed by different infants and shared no face-voice synchrony, temporal or
      intensity patterning, matching was likely based on detection of a more general
      affective valence common to the face and voice.

PMID- 24302852
TI  - Cost effectiveness of first-line treatment with doxorubicin/ifosfamide compared
      to trabectedin monotherapy in the management of advanced soft tissue sarcoma in
      Italy, Spain, and sweden.
AB  - Background. Doxorubicin/ifosfamide is a first-line systemic chemotherapy for the
      majority of advanced soft tissue sarcoma (ASTS) subtypes. Trabectedin is
      indicated for the treatment of ASTS after failure of anthracyclines and/or
      ifosfamide; however it is being increasingly used off-label as a first-line
      treatment. This study estimated the cost effectiveness of these two treatments in
      the first-line management of ASTS in Italy, Spain, and Sweden. Methods. A Markov
      model was constructed to estimate the cost effectiveness of
      doxorubicin/ifosfamide compared to trabectedin monotherapy, defined as the cost
      per QALY gained, in each country. Results. First-line treatment with
      doxorubicin/ifosfamide resulted in lower two-year healthcare costs and more QALYs
      than first-line treatment with trabectedin monotherapy in all three countries.
      Probabilistic sensitivity analysis showed that at a cost per QALY threshold of
      ?35,000, >90% of a cohort would be cost effectively treated with
      doxorubicin/ifosfamide compared to trabectedin monotherapy in all three
      countries. Conclusion. Within the model's limitations, first-line treatment of
      patients with ASTS with doxorubicin/ifosfamide instead of trabectedin monotherapy
      affords a cost-effective use of publicly funded healthcare resources in Italy,
      Spain, and Sweden and is therefore the preferred treatment in all three
      countries. These findings support the recommendation that trabectedin should
      remain a second-line treatment. 

PMID- 24302854
TI  - IMU-based online kinematic calibration of robot manipulator.
AB  - Robot calibration is a useful diagnostic method for improving the positioning
      accuracy in robot production and maintenance. An online robot self-calibration
      method based on inertial measurement unit (IMU) is presented in this paper. The
      method requires that the IMU is rigidly attached to the robot manipulator, which
      makes it possible to obtain the orientation of the manipulator with the
      orientation of the IMU in real time. This paper proposed an efficient approach
      which incorporates Factored Quaternion Algorithm (FQA) and Kalman Filter (KF) to
      estimate the orientation of the IMU. Then, an Extended Kalman Filter (EKF) is
      used to estimate kinematic parameter errors. Using this proposed orientation
      estimation method will result in improved reliability and accuracy in determining
      the orientation of the manipulator. Compared with the existing vision-based self
      calibration methods, the great advantage of this method is that it does not need
      the complex steps, such as camera calibration, images capture, and corner
      detection, which make the robot calibration procedure more autonomous in a
      dynamic manufacturing environment. Experimental studies on a GOOGOL GRB3016 robot
      show that this method has better accuracy, convenience, and effectiveness than
      vision-based methods. 

PMID- 24302855
TI  - A fast map merging algorithm in the field of multirobot SLAM.
AB  - In recent years, the research on single-robot simultaneous localization and
      mapping (SLAM) has made a great success. However, multirobot SLAM faces many
      challenging problems, including unknown robot poses, unshared map, and unstable
      communication. In this paper, a map merging algorithm based on virtual robot
      motion is proposed for multi-robot SLAM. The thinning algorithm is used to
      construct the skeleton of the grid map's empty area, and a mobile robot is
      simulated in one map. The simulated data is used as information sources in the
      other map to do partial map Monte Carlo localization; if localization succeeds,
      the relative pose hypotheses between the two maps can be computed easily. We
      verify these hypotheses using the rendezvous technique and use them as initial
      values to optimize the estimation by a heuristic random search algorithm. 

PMID- 24302856
TI  - Common force field thermodynamics of cholesterol.
AB  - Four different force fields are examined for dynamic characteristics using
      cholesterol as a case study. The extent to which various types of internal
      degrees of freedom become thermodynamically relevant is evaluated by means of
      principal component analysis. More complex degrees of freedom (angle bending,
      dihedral rotations) show a trend towards force field independence. Moreover,
      charge assignments for membrane-embedded compounds are revealed to be critical
      with significant impact on biological reasoning. 

PMID- 24302858
TI  - Fragmentation of chitosan by acids.
AB  - Fragmentation of chitosan in aqueous solution by hydrochloric acid was
      investigated. The kinetics of fragmentation, the number of chain scissions, and
      polydispersity of the fragments were followed by viscometry and size exclusion
      chromatography. The chemical structure and the degree of N-acetylation (DA) of
      the original chitosan and its fragments were examined by (1)H NMR spectroscopy
      and elemental analysis. The kinetic data indicates that the reaction was of first
      order. The results of polydispersity and the DA suggest that the selected
      experimental conditions (temperature and concentration of acid) were appropriate
      to obtain the fragments having the polydispersity and the DA similar to or
      slightly different from those of the original one. A procedure to estimate
      molecular weight of fragments as well as the number of chain scissions of the
      fragments under the experimental conditions was also proposed. 

PMID- 24302857
TI  - Characterization of the occult hepatitis B virus variants circulating among the
      blood donors from eastern India.
AB  - A previous study from West Bengal documented very high rate of occult HBV
      infection (OBI) among the HBsAg negative blood donors. This study was aimed to
      characterize the OBI strains circulating among the blood donors and to estimate
      the risk associated with the prevailing viral variants/mutants. Blood samples
      from 2195 voluntary blood donors were included in the study. HBsAg, HBeAg, anti
      HBc, and anti-HBs statuses of the samples were done by ELISA based detection. PCR
      amplification and sequencing were done to determine HBV genotypes, basal core
      promoter (BCP), and precore (Pre-C) mutations. Among the study samples, 268 were
      anti-HBc positive/HBsAg negative, among which 65 (24.25%) were HBV DNA positive.
      Phylogenetic analysis revealed the presence of HBV/D (87.23%), HBV/A (8.51%), and
      HBV/C (4.26%) (P < 0.0001). HBV/D3 (65.85%) was the significantly prevalent
      subgenotype over HBV/D2 (26.83%) and HBV/D1 (7.31%) (P = 0.0003). Considerable
      prevalence of differential BCP (1752C, 1753C, 1762T/1764A, 1753C+1762T/1764A,
      1773C, and 1814C) and reverse transcriptase (rt) gene (rtI91L, rtL93P, rtS106C,
      rtR110G, rtN118T, rtS119T, rtY126H, rtG127W/R, rtC136R, and rtY158H) mutations
      was identified. Association of specific HBV subgenotypes with OBI was interesting
      and needs further study. Clinically relevant mutations were prevalent among the
      OBI strains which are of serious concern. 

PMID- 24302859
TI  - Genotypic characterization of Azotobacteria isolated from Argentinean soils and
      plant-growth-promoting traits of selected strains with prospects for
      biofertilizer production.
AB  - The genetic diversity among 31 putative Azotobacter isolates obtained from
      agricultural and non-agricultural soils was assessed using rep-PCR genomic
      fingerprinting and identified to species level by ARDRA and partial 16S rRNA gene
      sequence analysis. High diversity was found among the isolates, identified as A.
      chroococcum, A. salinestris, and A. armeniacus. Selected isolates were
      characterized on the basis of phytohormone biosynthesis, nitrogenase activity,
      siderophore production, and phosphate solubilization. Indole-3 acetic-acid (IAA),
      gibberellin (GA3) and zeatin (Z) biosynthesis, nitrogenase activity, and
      siderophore production were found in all evaluated strains, with variation among
      them, but no phosphate solubilization was detected. Phytohormones excreted to the
      culture medium ranged in the following concentrations: 2.2-18.2 MU g IAA mL(-1),
      0.3-0.7 MU g GA3 mL(-1), and 0.5-1.2 MU g Z mL(-1). Seed inoculations with
      further selected Azotobacter strains and treatments with their cell-free cultures
      increased the number of seminal roots and root hairs in wheat seedlings. This
      latter effect was mimicked by treatments with IAA-pure solutions, but it was not
      related to bacterial root colonization. Our survey constitutes a first approach
      to the knowledge of Azotobacter species inhabiting Argentinean soils in three
      contrasting geographical regions. Moreover, this phenotypic characterization
      constitutes an important contribution to the selection of Azotobacter strains for
      biofertilizer formulations.

PMID- 24302860
TI  - MR image based approach for metal artifact reduction in X-ray CT.
AB  - For decades, computed tomography (CT) images have been widely used to discover
      valuable anatomical information. Metallic implants such as dental fillings cause
      severe streaking artifacts which significantly degrade the quality of CT images.
      In this paper, we propose a new method for metal-artifact reduction using
      complementary magnetic resonance (MR) images. The method exploits the
      possibilities which arise from the use of emergent trimodality systems. The
      proposed algorithm corrects reconstructed CT images. The projected data which is
      affected by dental fillings is detected and the missing projections are replaced
      with data obtained from a corresponding MR image. A simulation study was
      conducted in order to compare the reconstructed images with images reconstructed
      through linear interpolation, which is a common metal-artifact reduction
      technique. The results show that the proposed method is successful in reducing
      severe metal artifacts without introducing significant amount of secondary
      artifacts. 

PMID- 24302861
TI  - Prevalence of functional gastrointestinal disorders according to Rome III
      criteria in Italian morbidly obese patients.
AB  - The relationship between GI symptoms and obesity has yet to be completely
      clarified. AIM: To determine in a morbidly obese southern Italy adult population
      the prevalence of Functional Gastrointestinal Disorders (FGID) and its
      association with the presence of a Binge Eating (BE) behavior pattern. METHODS:
      Consecutive obese patients eligible for bariatric surgery and 100 Healthy
      Controls (HC) were recruited. All participants were questioned and scored for the
      presence of FGID according to Rome III criteria and for the presence or the
      frequency-intensity of a number of upper and lower GI symptoms. BE behavior
      pattern was assessed. RESULTS: One-hundred obese patients met the inclusion
      criteria. The prevalence of FGID was similar between obese patients and HC. There
      was a significant association between obese patients with BE behavior and
      postprandial distress syndrome (P = 0.04). Moreover, a significantly higher
      frequency-intensity score for epigastric fullness (1.23 +/- 0.45 versus 0.35 +/-
      0.13, P = 0.01) was found in obese patients with BE behavior compared to obese
      patients without. CONCLUSIONS: Obese patients with a BE behavior pattern showed a
      significantly higher prevalence of postprandial distress syndrome. A greater
      knowledge of the GI symptoms associated with obesity along with the
      pathophysiological mechanisms underlying will be important in the clinical
      management of these patients.

PMID- 24302862
TI  - Structural evolution of low-molecular-weight poly(ethylene oxide)-block
      polystyrene diblock copolymer thin film.
AB  - The structural evolution of low-molecular-weight poly(ethylene oxide)-block
      polystyrene (PEO-b-PS) diblock copolymer thin film with various initial film
      thicknesses on silicon substrate under thermal annealing was investigated by
      atomic force microscopy, optical microscopy, and contact angle measurement. At
      film thickness below half of the interlamellar spacing of the diblock copolymer
      (6.2 nm), the entire silicon is covered by a polymer brush with PEO blocks
      anchored on the Si substrate due to the substrate-induced effect. When the film
      is thicker than 6.2 nm, a dense polymer brush which is equal to half of an
      interlamellar layer was formed on the silicon, while the excess material dewet
      this layer to form droplets. The droplet surface was rich with PS block and the
      PEO block crystallized inside the bigger droplet to form spherulite.

PMID- 24302864
TI  - Monotonicity, concavity, and convexity of fractional derivative of functions.
AB  - The monotonicity of the solutions of a class of nonlinear fractional differential
      equations is studied first, and the existing results were extended. Then we
      discuss monotonicity, concavity, and convexity of fractional derivative of some
      functions and derive corresponding criteria. Several examples are provided to
      illustrate the applications of our results. 

PMID- 24302863
TI  - A new insight to bone turnover: role of omega-3 polyunsaturated fatty acids.
AB  - Background. Evidence has shown that long-chain polyunsaturated fatty acids
      (LCPUFA), especially the omega -3 fatty acids such as eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) are beneficial for bone health and turnover.
      Objectives. This review summarizes findings from both in vivo and in vitro
      studies and the effects of LC PUFA on bone metabolism, as well as the
      relationship with the oxidative stress, the inflammatory process, and obesity.
      Results. Some studies in humans indicate that LCPUFA can increase bone formation,
      affect peak bone mass in adolescents, and reduce bone loss. However, the cellular
      mechanisms of action of the LCPUFA are complex and involve modulation of fatty
      acid metabolites such as prostaglandins, resolvins and protectins, several
      signaling pathways, cytokines, and growth factors, although in certain aspects
      there is still some controversy. LCPUFA affect receptor activator of nuclear
      factor kappa beta (RANK), a receptor found on the osteoclast, causing bone
      resorption, which controls osteoclast formation. Conclusions. Since fatty acids
      are an endogenous source of reactive oxygen species, free radicals alter the
      process of bone turnover; however, although there are clinical evidences linking
      bone metabolism and dietary lipids, more clinical trials are necessary to prove
      whether omega -3 PUFA supplementation plays a major role in bone health. 

PMID- 24302865
TI  - Plucked human hair shafts and biomolecular medical research.
AB  - The hair follicle is a skin integument at the boundary between an organism and
      its immediate environment. The biological role of the human hair follicle has
      lost some of its ancestral importance. However, an indepth investigation of this
      miniorgan reveals hidden complexity with huge research potential. An essential
      consideration when dealing with human research is the awareness of potential harm
      and thus the absolute need not to harm--a rule aptly qualified by the Latin term
      "primum non nocere" (first do no harm). The plucked hair shaft offers such
      advantages. The use of stem cells found in hair follicles cells is gaining
      momentum in the field of regenerative medicine. Furthermore, current diagnostic
      and clinical applications of plucked hair follicles include their use as
      autologous and/or three-dimensional epidermal equivalents, together with their
      utilization as surrogate tissue in pharmacokinetic and pharmacodynamics studies.
      Consequently, the use of noninvasive diagnostic procedures on hair follicle
      shafts, posing as a surrogate molecular model for internal organs in the
      individual patient for a spectrum of human disease conditions, can possibly
      become a reality in the near future.

PMID- 24302866
TI  - Study on roadheader cutting load at different properties of coal and rock.
AB  - The mechanism of cutting process of roadheader with cutting head was researched,
      and the influences of properties of coal and rock on cutting load were deeply
      analyzed. Aimed at the defects of traditional calculation method of cutting load
      on fully expressing the complex cutting process of cutting head, the method of
      finite element simulation was proposed to simulate the dynamic cutting process.
      Aimed at the characteristics of coal and rock which affect the cutting load,
      several simulations with different firmness coefficient were taken repeatedly,
      and the relationship between three-axis force and firmness coefficient was
      derived. A comparative analysis of cutting pick load between simulation results
      and theoretical formula was carried out, and a consistency was achieved. Then
      cutting process with a total cutting head was carried out on this basis. The
      results show that the simulation analysis not only provides a reliable guarantee
      for the accurate calculation of the cutting head load and improves the efficiency
      of the cutting head cutting test but also offers a basis for selection of cutting
      head with different geological conditions of coal or rock. 

PMID- 24302867
TI  - Comparative study of laterite and bentonite based organoclays: implications of
      hydrophobic compounds remediation from aqueous solutions.
AB  - Four cost effective organoclays were synthesized, characterized, and studied for
      the sorption of hydrophobic compounds (edible oil/grease and hydrocarbon oil)
      from aqueous solutions. Organoclays were prepared by cation exchange reaction of
      lattice ions (present onto the surface of laterite and bentonite clay minerals)
      with two surfactants, hexadecyl trimethyl ammonium chloride (HDTMA-Cl) and
      tetradecyl trimethyl ammonium bromide (TDTMA-Br). Fourier transform infrared
      spectroscopy and scanning electron microscopy were used for the characterization
      of synthesized organoclays. It was found that the amount of surfactant loading
      and the nature of the surfactant molecules used in the syntheses of organoclay
      strongly affect the sorption capacity of the clay mineral. Further, it was found
      that both the laterite and bentonite based organoclays efficiently removed the
      edible and hydrocarbon oil content from lab prepared emulsions; however, the
      adsorption capacity of clay mineral was greatly influenced by the nature of
      hydrophobic compounds as well. 

PMID- 24302869
TI  - Multiple solutions for a class of Dirichlet double eigenvalue quasilinear
      elliptic systems involving the (p1,..., pn)-Laplacian operator.
AB  - Existence results of three weak solutions for a Dirichlet double eigenvalue
      quasilinear elliptic system involving the (p1,..., pn)-Laplacian operator, under
      suitable assumptions, are established. Our main tool is based on a recent three
      critical-point theorem obtained by Ricceri. We also give some examples to
      illustrate the obtained results.

PMID- 24302868
TI  - Genetic diversity and population genetics of mosquitoes (Diptera: Culicidae:
      Culex spp.) from the Sonoran Desert of North America.
AB  - The population genetics and phylogenetic relationships of Culex mosquitoes
      inhabiting the Sonoran Desert region of North America were studied using
      mitochondrial DNA and microsatellite molecular markers. Phylogenetic analyses of
      mitochondrial cytochrome c oxidase subunit I (COI) from mosquitoes collected over
      a wide geographic area, including the Baja California peninsula, and mainland
      localities in southern Arizona, USA and Sonora, Mexico, showed several well
      supported partitions corresponding to Cx. quinquefasciatus, Cx. tarsalis, and two
      unidentified species, Culex sp. 1 and sp. 2. Culex quinquefasciatus was found at
      all localities and was the most abundant species collected. Culex tarsalis was
      collected only at Tucson, Arizona and Guaymas, Sonora. The two unidentified
      species of Culex were most abundant at Navojoa in southern Sonora. Haplotype and
      nucleotide diversities in the COI gene segment were substantially lower in Cx.
      quinquefasciatus compared with the other three species. Analysis of molecular
      variance revealed little structure among seven populations of Cx.
      quinquefasciatus, whereas significant structure was found between the two
      populations of Cx. tarsalis. Evidence for an historical population expansion
      beginning in the Pleistocene was found for Cx. tarsalis. Possible explanations
      for the large differences in genetic diversity between Cx. quinquefasciatus and
      the other species of Culex are presented. 

PMID- 24302870
TI  - A systematic review and meta-analysis to assess patient-reported outcomes after
      lung cancer surgery.
AB  - The main objective of this review was to systematically review, assess, and
      report on the studies that have assessed health related quality of life (HRQOL)
      after VATS and thoracotomy for resection of lung cancer. We performed a
      systematic review of six databases. The Downs and Black tool was used to assess
      the risk of bias. Five studies were included. In general, patients undergoing
      VATS have a better HRQOL when compared to thoracotomy; however, there was a high
      risk of bias in the included studies. The consistent use of a lung cancer
      specific questionnaire for measuring HRQOL after surgery is encouraged. 

PMID- 24302871
TI  - Analytical and experimental analysis of a free link in contact with a granular
      medium.
AB  - In this study, the experimental and the simulation results for a planar free link
      impacting a granular medium are analyzed. The resistance force of the granular
      medium on the body from the moment of the impact until the body stops is very
      important. Horizontal and vertical static resistance forces developed by
      theoretical and empirical approaches are considered. The penetrating depth of the
      impacting end of the free link increases with the increase of the initial
      impacting velocity. We define the stopping time as the time interval from the
      moment of impact until the vertical velocity of the link end is zero. The
      stopping time of the end decreases as the initial velocity increases. The faster
      the end of the link impacts the surface of the granular medium, the sooner it
      will come to a stop. This phenomenon involves how rapidly a free link strikes the
      granular medium and how it slows down upon contact. 

PMID- 24302872
TI  - Lifetime paid work and mental health problems among poor urban 9-to-13-year-old
      children in Brazil.
AB  - OBJECTIVE: To verify if emotional/behavioral problems are associated with
      lifetime paid work in poor urban children, when taking into account other
      potential correlates. METHODS: Cross-sectional study focused on 9-to-13-year-old
      children (n = 212). In a probabilistic sample of clusters of eligible households
      (women 15-49 years and son/daughter <18 years), one mother-child pair was
      randomly selected per household (n = 813; response rate = 82.4%). CBCL/6-18
      identified child emotional/behavioral problems. Potential correlates include
      child gender and age, socioeconomic status/SES, maternal education, parental
      working status, and family social isolation, among others. Multivariate analysis
      examined the relationship between emotional/behavioral problems and lifetime paid
      work in the presence of significant correlates. FINDINGS: All work activities
      were non-harmful (e.g., selling fruits, helping parents at their small business,
      and baby sitting). Children with lower SES and socially isolated were more
      involved in paid work than less disadvantaged peers. Children ever exposed to
      paid work were four times more likely to present anxiety/depression symptoms at a
      clinical level compared to non-exposed children. Multivariate modeling identified
      three independent correlates: child pure internalizing problems, social
      isolation, and low SES. CONCLUSION: There is an association between lifetime
      exposure to exclusively non-harmful paid work activities and pure internalizing
      problems even when considering SES variability and family social isolation.

PMID- 24302873
TI  - Conduct symptoms and emotion recognition in adolescent boys with externalization
      problems.
AB  - BACKGROUND: In adults with antisocial personality disorder, marked alterations in
      the recognition of facial affect were described. Less consistent data are
      available on the emotion recognition in adolescents with externalization
      problems. The aim of the present study was to assess the relation between the
      recognition of emotions and conduct symptoms in adolescent boys with
      externalization problems. METHODS: Adolescent boys with externalization problems
      referred to Vadaskert Child Psychiatry Hospital participated in the study after
      informed consent (N = 114, 11-17 years, mean = 13.4). The conduct problems scale
      of the strengths and difficulties questionnaire (parent and self-report) was
      used. The performance in a facial emotion recognition test was assessed. RESULTS:
      Conduct problems score (parent and self-report) was inversely correlated with the
      overall emotion recognition. In the self-report, conduct problems score was
      inversely correlated with the recognition of anger, fear, and sadness.
      Adolescents with high conduct problems scores were significantly worse in the
      recognition of fear, sadness, and overall recognition than adolescents with low
      conduct scores, irrespective of age and IQ. CONCLUSIONS: Our results suggest that
      impaired emotion recognition is dimensionally related to conduct problems and
      might have importance in the development of antisocial behavior.

PMID- 24302874
TI  - Parents' attitudes toward oral rehydration therapy in children with mild-to
      moderate dehydration.
AB  - OBJECTIVE: According to current guidelines, the first line of treatment for mild
      to-moderate dehydration is oral rehydration; the second line is rehydration
      through a nasogastric tube. Both methods are widely underused. This study was
      conducted to evaluate parents' attitudes towards rehydration methods used in
      pediatric emergency departments. DESIGN: 100 questionnaires were distributed to
      parents of children who visited emergency room due to gastroenteritis and
      suspected dehydration. RESULTS: 75 of the parents expected their child to get IV
      fluids. 49 of them would refuse to consider oral rehydration. 75 of the parents
      would refuse to consider insertion of nasogastric tube. Parents whose children
      were previously treated intravenously tended to be less likely to agree to oral
      treatment. Parents were more prone to decline oral rehydration if the main
      measurement of dehydration was the child's clinical appearance, clinical
      appearance with vomiting, or child's refusal to drink and were more likely to
      agree if the main measurement was diarrhea, diarrhea with clinical appearance, or
      clinical personnel opinion. CONCLUSIONS: This is the first study to examine
      parents' expectations. We found that in the majority of cases, parents'
      expectations contradict current guidelines. Efforts should be taken to educate
      parents in order to allow full implementation of the guidelines.

PMID- 24302875
TI  - Large-scale plantlet conversion and ex vitro transplantation efficiency of
      Siberian ginseng by bioreactor culture.
AB  - To achieve large-scale low-cost ex vitro acclimatization of Siberian ginseng
      plants, heart- and torpedo-shaped secondary somatic embryos (SEs) induced from
      germinated SEs on agar medium were collected and then inoculated to 10-l bubble
      column bioreactor, respectively. For plantlet conversion, inoculation of torpedo
      shaped secondary SEs was more effective than heart-shaped SEs. TS2 (culture of
      torpedo-shaped SEs in a bioreactor with a 2-week subculture interval) plantlets
      had a higher root number and leaf number and larger leaf area than did HS3
      (culture of heart-shaped SEs in a bioreactor with a 3-week subculture interval)
      and HS2 (culture of heart-shaped SEs in a bioreactor with a 2-week subculture
      interval) plantlets. Of these converted plants, TS2 plantlets had higher survival
      rate (83.7%) and growth characteristics after transplantation in a simple shed
      covered with a 50% sunshade net only for 6 months. TS2 plantlets also showed
      significantly lower H2O2 content and significantly increased superoxide dismutase
      (SOD), glutathione peroxidase (GPX), and glutathione transferase (GST) expression
      levels as compared to HS2 plants when exposure to ex vitro conditions. 

PMID- 24302876
TI  - Determination of decabrominated diphenyl ether in soils by Soxhlet extraction and
      high performance liquid chromatography.
AB  - This study described the development of a method based on Soxhlet extraction
      combining high performance liquid chromatography (Soxhlet-HPLC) for the accurate
      detection of BDE-209 in soils. The solvent effect of working standard solutions
      in HPLC was discussed. Results showed that 1:1 of methanol and acetone was the
      optimal condition which could totally dissolve the BDE-209 in environmental
      samples and avoid the decrease of the peak area and the peak deformation
      difference of BDE-209 in HPLC. The preliminary experiment was conducted on the
      configured grassland (1 MU g/g) to validate the method feasibility. The method
      produced reliable reproducibility, simulated soils (n = 4) RSD 1.0%, and was
      further verified by the analysis e-waste contaminated soils, RSD range 5.9-11.4%.
      The contamination level of BDE-209 in burning site was consistent with the
      previous study of Longtang town but lower than Guiyu town, and higher
      concentration of BDE-209 in paddy field mainly resulted from the long-standing
      disassembling area nearby. This accurate and fast method was successfully
      developed to extract and analyze BDE-209 in soil samples, showing its potential
      use for replacing GC to determinate BDE-209 in soil samples.

PMID- 24302877
TI  - Novel silica-based hybrid adsorbents: lead(II) adsorption isotherms.
AB  - Water pollution caused by the lead(II) from the spent liquor has caught much
      attention. The research from the theoretical model to application fundaments is
      of vital importance. In this study, lead(II) adsorption isotherms are
      investigated using a series of hybrid membranes containing mercapto groups (-SH
      groups) as the hybrid adsorbents. To determine the best fitting equation, the
      experimental data were analyzed using six two-parameter isotherm equations (i.e.,
      Langmuir, Freundlich, Dubinin-Radushkevich (D-R), Temkin, Harkins-Jura, and
      Halsey isotherm models). It was found that the lead(II) adsorption on these
      samples followed the Freundlich, Dubinin-Radushkevich (D-R), and Halsey isotherm
      models. Moreover, the mean free energy of adsorption was calculated using Dubinin
      Radushkevich (D-R) isotherm model and it was confirmed that the adsorption
      process was physical in nature. These findings are very meaningful in the removal
      of lead(II) ions from water using the hybrid membranes as adsorbents. 

PMID- 24302878
TI  - Dengue virus type 2: protein binding and active replication in human central
      nervous system cells.
AB  - An increased number of dengue cases with neurological complications have been
      reported in recent years. The lack of reliable animal models for dengue has
      hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in
      vivo. We further investigate the tropism of DENV for the human central nervous
      system (CNS), characterizing DENV interactions with cell surface proteins in
      human CNS cells by virus overlay protein binding assays (VOPBA) and
      coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa)
      from the gray matter bound the entire virus particle, whereas only a 70 kDa
      protein bound in white matter. The coimmunoprecipitation assays revealed three
      proteins from gray matter consistently binding virus particles, one clearly
      distinguishable protein (~32 kDa) and two less apparent proteins (100 and 130
      kDa). Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of
      human CNS treated with DENV-2, which also stained positive for NeuH, a neuron
      specific marker. Thus, our results indicate (1) that DENV-2 exhibited a direct
      tropism for human neurons and (2) that human neurons sustain an active DENV
      replication as was demonstrated by the presence of the NS3 viral antigen in
      primary cultures of these cells treated with DENV-2.

PMID- 24302879
TI  - Photoresponsive wettability in monolayer films from sinapinic acid.
AB  - Sinapinic acid is an interesting material because it is both antioxidant and
      antibacterial agent. In addition, when illuminated with ultraviolet light, it can
      exhibit the so-called photodimerization process. In this paper, we report on the
      investigation of monolayer films from 3,5-dimethoxy-4-hydroxycinnamic acid
      (sinapinic acid, SinA) deposited onto poly(allylamine hydrochloride), PAH, films.
      SinA monolayers were prepared by using the layer-by-layer (LbL) self-assembly
      technique. Adsorption kinetics curves were well fitted by a biexponential
      function suggesting that the adsorption process is determined by two mechanisms:
      nucleation and growth of aggregates. By using wetting contact angle analysis, we
      have found that SinA monolayers exhibit photoresponsive wettability under UV
      irradiation (365 nm); that is, wettability decreases with increasing UV
      irradiation time. The photoresponse of wettability was attributed to
      photodimerization process. This hypothesis was supported by the dependence of
      surface morphological structure and absorption on UV irradiation time. The
      mechanism found in the well-known transcinnamic acid crystals is used to explain
      the photodimerization process in SinA monolayers.

PMID- 24302880
TI  - Modeling and optimization of the multiobjective stochastic joint replenishment
      and delivery problem under supply chain environment.
AB  - As a practical inventory and transportation problem, it is important to
      synthesize several objectives for the joint replenishment and delivery (JRD)
      decision. In this paper, a new multiobjective stochastic JRD (MSJRD) of the one
      warehouse and n-retailer systems considering the balance of service level and
      total cost simultaneously is proposed. The goal of this problem is to decide the
      reasonable replenishment interval, safety stock factor, and traveling routing.
      Secondly, two approaches are designed to handle this complex multi-objective
      optimization problem. Linear programming (LP) approach converts the multi
      objective to single objective, while a multi-objective evolution algorithm (MOEA)
      solves a multi-objective problem directly. Thirdly, three intelligent
      optimization algorithms, differential evolution algorithm (DE), hybrid DE (HDE),
      and genetic algorithm (GA), are utilized in LP-based and MOEA-based approaches.
      Results of the MSJRD with LP-based and MOEA-based approaches are compared by a
      contrastive numerical example. To analyses the nondominated solution of MOEA, a
      metric is also used to measure the distribution of the last generation solution.
      Results show that HDE outperforms DE and GA whenever LP or MOEA is adopted. 

PMID- 24302882
TI  - The distribution and composition characteristics of siliceous rocks from Qinzhou
      Bay-Hangzhou Bay joint belt, South China: constraint on the tectonic evolution of
      plates in South China.
AB  - The Qinzhou Bay-Hangzhou Bay joint belt is a significant tectonic zone between
      the Yangtze and Cathaysian plates, where plentiful hydrothermal siliceous rocks
      are generated. Here, the authors studied the distribution of the siliceous rocks
      in the whole tectonic zone, which indicated that the tensional setting was
      facilitating the development of siliceous rocks of hydrothermal genesis.
      According to the geochemical characteristics, the Neopalaeozoic siliceous rocks
      in the north segment of the Qinzhou Bay-Hangzhou Bay joint belt denoted its
      limited width. In comparison, the Neopalaeozoic Qinzhou Bay-Hangzhou Bay joint
      belt was diverse for its ocean basin in the different segments and possibly had
      subduction only in the south segment. The ocean basin of the north and middle
      segments was limited in its width without subduction and possibly existed as a
      rift trough that was unable to resist the terrigenous input. In the north segment
      of the Qinzhou Bay-Hangzhou Bay joint belt, the strata of hydrothermal siliceous
      rocks in Dongxiang copper-polymetallic ore deposit exhibited alternative cycles
      with the marine volcanic rocks, volcanic tuff, and metal sulphide. These
      sedimentary systems were formed in different circumstances, whose alternative
      cycles indicated the release of internal energy in several cycles gradually from
      strong to weak. 

PMID- 24302881
TI  - Peculiar evolutionary history of miR390-guided TAS3-like genes in land plants.
AB  - PCR-based approach was used as a phylogenetic profiling tool to probe genomic DNA
      samples from representatives of evolutionary distant moss taxa, namely, classes
      Bryopsida, Tetraphidopsida, Polytrichopsida, Andreaeopsida, and Sphagnopsida. We
      found relatives of all Physcomitrella patens miR390 and TAS3-like loci in these
      plant taxa excluding Sphagnopsida. Importantly, cloning and sequencing of
      Marchantia polymorpha genomic DNA showed miR390 and TAS3-like sequences which
      were also found among genomic reads of M. polymorpha at NCBI database. Our data
      suggest that the ancient plant miR390-dependent TAS molecular machinery firstly
      evolved to target AP2-like mRNAs in Marchantiophyta and only then both ARF- and
      AP2-specific mRNAs in mosses. The presented analysis shows that moss TAS3
      families may undergone losses of tasiAP2 sites during evolution toward ferns and
      seed plants. These data confirm that miR390-guided genes coding for ARF- and AP2
      specific ta-siRNAs have been gradually changed during land plant evolution. 

PMID- 24302883
TI  - Evaluation of permanent deformation of CRM-reinforced SMA and its correlation
      with dynamic stiffness and dynamic creep.
AB  - Today, rapid economic and industrial growth generates increasing amounts of waste
      materials such as waste tyre rubber. Attempts to inspire a green technology which
      is more environmentally friendly that can produce economic value are a major
      consideration in the utilization of waste materials. The aim of this study is to
      evaluate the effect of waste tyre rubber (crumb rubber modifier (CRM)), in stone
      mastic asphalt (SMA 20) performance. The virgin bitumen (80/100) penetration
      grade was used, modified with crumb rubber at four different modification levels,
      namely, 6%, 12%, 16%, and 20% by weight of the bitumen. The testing undertaken on
      the asphalt mix comprises the indirect tensile (dynamic stiffness), dynamic
      creep, and wheel tracking tests. By the experimentation, the appropriate amount
      of CRM was found to be 16% by weight of bitumen. The results show that the
      addition of CRM into the mixture has an obvious significant effect on the
      performance properties of SMA which could improve the mixture's resistance
      against permanent deformation. Further, higher correlation coefficient was
      obtained between the rut depth and permanent strain as compared to resilient
      modulus; thus dynamic creep test might be a more reliable test in evaluating the
      rut resistance of asphalt mixture. 

PMID- 24302885
TI  - An HDAC in the cytoplasm, not the nucleus, plays a pathogenic role in
      Huntington's disease.

PMID- 24302884
TI  - HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin
      and ameliorate neurodegeneration.
AB  - Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a
      glutamine-rich domain. We hypothesised that it may be involved in the molecular
      pathogenesis of Huntington's disease (HD), a protein-folding neurodegenerative
      disorder caused by an aggregation-prone polyglutamine expansion in the huntingtin
      protein. We found that HDAC4 associates with huntingtin in a polyglutamine-length
      dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4
      reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript
      levels, and rescued neuronal and cortico-striatal synaptic function in HD mouse
      models. This was accompanied by an improvement in motor coordination,
      neurological phenotypes, and increased lifespan. Surprisingly, HDAC4 reduction
      had no effect on global transcriptional dysfunction and did not modulate nuclear
      huntingtin aggregation. Our results define a crucial role for the cytoplasmic
      aggregation process in the molecular pathology of HD. HDAC4 reduction presents a
      novel strategy for targeting huntingtin aggregation, which may be amenable to
      small-molecule therapeutics. 

PMID- 24302886
TI  - ANXUR receptor-like kinases coordinate cell wall integrity with growth at the
      pollen tube tip via NADPH oxidases.
AB  - It has become increasingly apparent that the extracellular matrix (ECM), which in
      plants corresponds to the cell wall, can influence intracellular activities in
      ways that go far beyond their supposedly passive mechanical support. In plants,
      growing cells use mechanisms sensing cell wall integrity to coordinate cell wall
      performance with the internal growth machinery to avoid growth cessation or loss
      of integrity. How this coordination precisely works is unknown. Previously, we
      reported that in the tip-growing pollen tube the ANXUR receptor-like kinases
      (RLKs) of the CrRLK1L subfamily are essential to sustain growth without loss of
      cell wall integrity in Arabidopsis. Here, we show that over-expression of the
      ANXUR RLKs inhibits growth by over-activating exocytosis and the over
      accumulation of secreted cell wall material. Moreover, the characterization of
      mutations in two partially redundant pollen-expressed NADPH oxidases coupled with
      genetic interaction studies demonstrate that the ANXUR RLKs function upstream of
      these NADPH oxidases. Using the H2O2-sensitive HyPer and the Ca2+-sensitive
      YC3.60 sensors in NADPH oxidase-deficient mutants, we reveal that NADPH oxidases
      generate tip-localized, pulsating H2O2 production that functions, possibly
      through Ca2+ channel activation, to maintain a steady tip-focused Ca2+ gradient
      during growth. Our findings support a model where ECM-sensing receptors regulate
      reactive oxygen species production, Ca2+ homeostasis, and exocytosis to
      coordinate ECM-performance with the internal growth machinery.

PMID- 24302887
TI  - Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell
      migration and cell polarity by direct modulation of the actin cytoskeleton.
AB  - Planar cell polarity (PCP) regulates cell alignment required for collective cell
      movement during embryonic development. This requires PCP/PCP effector proteins,
      some of which also play essential roles in ciliogenesis, highlighting the long
      standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was
      recently shown to regulate both ciliogenesis and collective cell movement, but
      the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by
      direct modulation of the actin cytoskeleton. These studies were made possible by
      recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes
      reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac
      outflow tract and cochlea defects associated with PCP perturbation. We observed
      Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2,
      Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required
      for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in
      the cytoplasm, where it is localized in the actin cytoskeleton and in focal
      adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin
      filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin
      cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin
      filaments. Significantly, organization of the actin filaments and focal contacts
      were markedly changed in Wdpcp-deficient cells. This was associated with
      decreased membrane ruffling, failure to establish cell polarity, and loss of
      directional cell migration. These results suggest the PCP defects in Wdpcp
      mutants are not caused by loss of cilia, but by direct disruption of the actin
      cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and
      yet exhibits PCP defects. Together, these findings provide the first evidence, to
      our knowledge, that a PCP component required for ciliogenesis can directly
      modulate the actin cytoskeleton to regulate cell polarity and directional cell
      migration. 

PMID- 24302888
TI  - Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling
      through targeting patched turnover.
AB  - Hedgehog signaling plays conserved roles in controlling embryonic development;
      its dysregulation has been implicated in many human diseases including cancers.
      Hedgehog signaling has an unusual reception system consisting of two
      transmembrane proteins, Patched receptor and Smoothened signal transducer.
      Although activation of Smoothened and its downstream signal transduction have
      been intensively studied, less is known about how Patched receptor is regulated,
      and particularly how this regulation contributes to appropriate Hedgehog signal
      transduction. Here we identified a novel role of Smurf E3 ligase in regulating
      Hedgehog signaling by controlling Patched ubiquitination and turnover. Moreover,
      we showed that Smurf-mediated Patched ubiquitination depends on Smo activity in
      wing discs. Mechanistically, we found that Smo interacts with Smurf and promotes
      it to mediate Patched ubiquitination by targeting the K1261 site in Ptc. The
      further mathematic modeling analysis reveals that a bidirectional control of
      activation of Smo involving Smurf and Patched is important for signal-receiving
      cells to precisely interpret external signals, thereby maintaining Hedgehog
      signaling reliability. Finally, our data revealed an evolutionarily conserved
      role of Smurf proteins in controlling Hh signaling by targeting Ptc during
      development. 

PMID- 24302889
TI  - A SCARECROW-RETINOBLASTOMA protein network controls protective quiescence in the
      Arabidopsis root stem cell organizer.
AB  - Quiescent long-term somatic stem cells reside in plant and animal stem cell
      niches. Within the Arabidopsis root stem cell population, the Quiescent Centre
      (QC), which contains slowly dividing cells, maintains surrounding short-term stem
      cells and may act as a long-term reservoir for stem cells. The RETINOBLASTOMA
      RELATED (RBR) protein cell-autonomously reinforces mitotic quiescence in the QC.
      RBR interacts with the stem cell transcription factor SCARECROW (SCR) through an
      LxCxE motif. Disruption of this interaction by point mutation in SCR or RBR
      promotes asymmetric divisions in the QC that renew short-term stem cells.
      Analysis of the in vivo role of quiescence in the root stem cell niche reveals
      that slow cycling within the QC is not needed for structural integrity of the
      niche but allows the growing root to cope with DNA damage. 

PMID- 24302891
TI  - Same song, different audience: pharmaceutical promotion targeting non-physician
      health care providers.

PMID- 24302892
TI  - Interactions between non-physician clinicians and industry: a systematic review.
AB  - BACKGROUND: With increasing restrictions placed on physician-industry
      interactions, industry marketing may target other health professionals. Recent
      health policy developments confer even greater importance on the decision making
      of non-physician clinicians. The purpose of this systematic review is to examine
      the types and implications of non-physician clinician-industry interactions in
      clinical practice. METHODS AND FINDINGS: We searched MEDLINE and Web of Science
      from January 1, 1946, through June 24, 2013, according to PRISMA guidelines. Non
      physician clinicians eligible for inclusion were: Registered Nurses, nurse
      prescribers, Physician Assistants, pharmacists, dieticians, and physical or
      occupational therapists; trainee samples were excluded. Fifteen studies met
      inclusion criteria. Data were synthesized qualitatively into eight outcome
      domains: nature and frequency of industry interactions; attitudes toward
      industry; perceived ethical acceptability of interactions; perceived marketing
      influence; perceived reliability of industry information; preparation for
      industry interactions; reactions to industry relations policy; and management of
      industry interactions. Non-physician clinicians reported interacting with the
      pharmaceutical and infant formula industries. Clinicians across disciplines met
      with pharmaceutical representatives regularly and relied on them for practice
      information. Clinicians frequently received industry "information," attended
      sponsored "education," and acted as distributors for similar materials targeted
      at patients. Clinicians generally regarded this as an ethical use of industry
      resources, and felt they could detect "promotion" while benefiting from industry
      "information." Free samples were among the most approved and common ways that
      clinicians interacted with industry. Included studies were observational and of
      varying methodological rigor; thus, these findings may not be generalizable. This
      review is, however, the first to our knowledge to provide a descriptive analysis
      of this literature. CONCLUSIONS: Non-physician clinicians' generally positive
      attitudes toward industry interactions, despite their recognition of issues
      related to bias, suggest that industry interactions are normalized in clinical
      practice across non-physician disciplines. Industry relations policy should
      address all disciplines and be implemented consistently in order to mitigate
      conflicts of interest and address such interactions' potential to affect patient
      care. Please see later in the article for the Editors' Summary.

PMID- 24302894
TI  - Neural dynamics of reward probability coding: a Magnetoencephalographic study in
      humans.
AB  - Prediction of future rewards and discrepancy between actual and expected outcomes
      (prediction error) are crucial signals for adaptive behavior. In humans, a number
      of fMRI studies demonstrated that reward probability modulates these two signals
      in a large brain network. Yet, the spatio-temporal dynamics underlying the neural
      coding of reward probability remains unknown. Here, using magnetoencephalography,
      we investigated the neural dynamics of prediction and reward prediction error
      computations while subjects learned to associate cues of slot machines with
      monetary rewards with different probabilities. We showed that event-related
      magnetic fields (ERFs) arising from the visual cortex coded the expected reward
      value 155 ms after the cue, demonstrating that reward value signals emerge early
      in the visual stream. Moreover, a prediction error was reflected in ERF peaking
      300 ms after the rewarded outcome and showing decreasing amplitude with higher
      reward probability. This prediction error signal was generated in a network
      including the anterior and posterior cingulate cortex. These findings pinpoint
      the spatio-temporal characteristics underlying reward probability coding.
      Together, our results provide insights into the neural dynamics underlying the
      ability to learn probabilistic stimuli-reward contingencies. 

PMID- 24302890
TI  - Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR
      project: a modeling study.
AB  - BACKGROUND: Assessing the mortality impact of the 2009 influenza A H1N1 virus
      (H1N1pdm09) is essential for optimizing public health responses to future
      pandemics. The World Health Organization reported 18,631 laboratory-confirmed
      pandemic deaths, but the total pandemic mortality burden was substantially
      higher. We estimated the 2009 pandemic mortality burden through statistical
      modeling of mortality data from multiple countries. METHODS AND FINDINGS: We
      obtained weekly virology and underlying cause-of-death mortality time series for
      2005-2009 for 20 countries covering ~35% of the world population. We applied a
      multivariate linear regression model to estimate pandemic respiratory mortality
      in each collaborating country. We then used these results plus ten country
      indicators in a multiple imputation model to project the mortality burden in all
      world countries. Between 123,000 and 203,000 pandemic respiratory deaths were
      estimated globally for the last 9 mo of 2009. The majority (62%-85%) were
      attributed to persons under 65 y of age. We observed a striking regional
      heterogeneity, with almost 20-fold higher mortality in some countries in the
      Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths
      to influenza in an average pre-pandemic season, with only 19% in persons <65 y.
      Limitations include lack of representation of low-income countries among single
      country estimates and an inability to study subsequent pandemic waves (2010
      2012). CONCLUSIONS: We estimate that 2009 global pandemic respiratory mortality
      was ~10-fold higher than the World Health Organization's laboratory-confirmed
      mortality count. Although the pandemic mortality estimate was similar in
      magnitude to that of seasonal influenza, a marked shift toward mortality among
      persons <65 y of age occurred, so that many more life-years were lost. The burden
      varied greatly among countries, corroborating early reports of far greater
      pandemic severity in the Americas than in Australia, New Zealand, and Europe. A
      collaborative network to collect and analyze mortality and hospitalization
      surveillance data is needed to rapidly establish the severity of future
      pandemics. Please see later in the article for the Editors' Summary.

PMID- 24302896
TI  - Editorial perspective of the Research Topic "Deciphering serotonin's role in
      neurodevelopment".

PMID- 24302895
TI  - The NO/cGMP pathway inhibits transient cAMP signals through the activation of
      PDE2 in striatal neurons.
AB  - The NO-cGMP signaling plays an important role in the regulation of striatal
      function although the mechanisms of action of cGMP specifically in medium spiny
      neurons (MSNs) remain unclear. Using genetically encoded fluorescent biosensors,
      including a novel Epac-based sensor (EPAC-S(H150)) with increased sensitivity for
      cAMP, we analyze the cGMP response to NO and whether it affected cAMP/PKA
      signaling in MSNs. The Cygnet2 sensor for cGMP reported large responses to NO
      donors in both striatonigral and striatopallidal MSNs, this cGMP signal was
      controlled partially by PDE2. At the level of cAMP brief forskolin stimulations
      produced transient cAMP signals which differed between D1 and D2 MSNs. NO
      inhibited these cAMP transients through cGMP-dependent PDE2 activation, an effect
      that was translated and magnified downstream of cAMP, at the level of PKA. PDE2
      thus appears as a critical effector of NO which modulates the post-synaptic
      response of MSNs to dopaminergic transmission. 

PMID- 24302897
TI  - Early gene expression changes in spinal cord from SOD1(G93A) Amyotrophic Lateral
      Sclerosis animal model.
AB  - Amyotrophic Lateral Sclerosis (ALS) is an adult-onset and fast progression
      neurodegenerative disease that leads to the loss of motor neurons. Mechanisms of
      selective motor neuron loss in ALS are unknown. The early events occurring in the
      spinal cord that may contribute to motor neuron death are not described, neither
      astrocytes participation in the pre-symptomatic phases of the disease. In order
      to identify ALS early events, we performed a microarray analysis employing a
      whole mouse genome platform to evaluate the gene expression pattern of lumbar
      spinal cords of transgenic SOD1(G93A) mice and their littermate controls at pre
      symptomatic ages of 40 and 80 days. Differentially expressed genes were
      identified by means of the Bioconductor packages Agi4*44Preprocess and limma.
      FunNet web based tool was used for analysis of over-represented pathways.
      Furthermore, immunolabeled astrocytes from 40 and 80 days old mice were submitted
      to laser microdissection and RNA was extracted for evaluation of a selected gene
      by qPCR. Statistical analysis has pointed to 492 differentially expressed genes
      (155 up and 337 down regulated) in 40 days and 1105 (433 up and 672 down) in 80
      days old ALS mice. KEGG analysis demonstrated the over-represented pathways tight
      junction, antigen processing and presentation, oxidative phosphorylation,
      endocytosis, chemokine signaling pathway, ubiquitin mediated proteolysis and
      glutamatergic synapse at both pre-symptomatic ages. Ube2i gene expression was
      evaluated in astrocytes from both transgenic ages, being up regulated in 40 and
      80 days astrocytes enriched samples. Our data points to important early molecular
      events occurring in pre-symptomatic phases of ALS in mouse model. Early
      SUMOylation process linked to astrocytes might account to non-autonomous cell
      toxicity in ALS. Further studies on the signaling pathways presented here may
      provide new insights to better understand the events triggering motor neuron
      death in this devastating disorder. 

PMID- 24302899
TI  - Gradual extinction prevents the return of fear: implications for the discovery of
      state.
AB  - Fear memories are notoriously difficult to erase, often recovering over time. The
      longstanding explanation for this finding is that, in extinction training, a new
      memory is formed that competes with the old one for expression but does not
      otherwise modify it. This explanation is at odds with traditional models of
      learning such as Rescorla-Wagner and reinforcement learning. A possible
      reconciliation that was recently suggested is that extinction training leads to
      the inference of a new state that is different from the state that was in effect
      in the original training. This solution, however, raises a new question: under
      what conditions are new states, or new memories formed? Theoretical accounts
      implicate persistent large prediction errors in this process. As a test of this
      idea, we reasoned that careful design of the reinforcement schedule during
      extinction training could reduce these prediction errors enough to prevent the
      formation of a new memory, while still decreasing reinforcement sufficiently to
      drive modification of the old fear memory. In two Pavlovian fear-conditioning
      experiments, we show that gradually reducing the frequency of aversive stimuli,
      rather than eliminating them abruptly, prevents the recovery of fear. This
      finding has important implications for theories of state discovery in
      reinforcement learning. 

PMID- 24302898
TI  - Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat
      (Heterocephalus glaber).
AB  - The naked mole-rat (Heterocephalus glaber) is a small fossorial rodent with
      specialized dentition that is reflected by the large cortical area dedicated to
      representation of the prominent incisors. Due to naked mole-rats' behavioral
      reliance on the incisors for digging and for manipulating objects, as well as
      their ability to move the lower incisors independently, we hypothesized that
      expanded somatosensory representations of the incisors would be present within
      the cerebellum in order to accommodate a greater degree of proprioceptive,
      cutaneous, and periodontal input. Multiunit electrophysiological recordings
      targeting the ansiform lobule were used to investigate tactile inputs from
      receptive fields on the entire body with a focus on the incisors. Similar to
      other rodents, a fractured somatotopy appeared to be present with discrete
      representations of the same receptive fields repeated within each folium of the
      cerebellum. These findings confirm the presence of somatosensory inputs to a
      large area of the naked mole-rat cerebellum with particularly extensive
      representations of the lower incisors and mystacial vibrissae. We speculate that
      these extensive inputs facilitate processing of tactile cues as part of a
      sensorimotor integration network that optimizes how sensory stimuli are acquired
      through active exploration and in turn adjusts motor outputs (such as independent
      movement of the lower incisors). These results highlight the diverse sensory
      specializations and corresponding brain organizational schemes that have evolved
      in different mammals to facilitate exploration of and interaction with their
      environment. 

PMID- 24302900
TI  - Embodying an outgroup: the role of racial bias and the effect of multisensory
      processing in somatosensory remapping.
AB  - We come to understand other people's physical and mental states by re-mapping
      their bodily states onto our sensorimotor system. This process, also called
      somatosensory resonance, is an essential ability for social cognition and is
      stronger when observing ingroup than outgroup members. Here we investigated,
      first, whether implicit racial bias constrains somatosensory resonance, and
      second, whether increasing the ingroup/outgroup perceived physical similarity
      results in an increase in the somatosensory resonance for outgroup members. We
      used the Visual Remapping of Touch effect as an index of individuals' ability in
      resonating with the others, and the Implicit Association Test to measure racial
      bias. In Experiment 1, participants were asked to detect near-threshold tactile
      stimuli delivered to their own face while viewing either an ingroup or an
      outgroup face receiving a similar stimulation. Our results showed that
      individuals' tactile accuracy when viewing an outgroup face being touched was
      negatively correlated to their implicit racial bias. In Experiment 2,
      participants received the interpersonal multisensory stimulation (IMS) while
      observing an outgroup member. IMS has been found to increase the perceived
      physical similarity between the observer's and the observed body. We tested
      whether such increase in ingroup/outgroup perceived physical similarity increased
      the remapping ability for outgroup members. We found that after sharing IMS
      experience with an outgroup member, tactile accuracy when viewing touch on
      outgroup faces increased. Interestingly, participants with stronger implicit bias
      against the outgroup showed larger positive change in the remapping. We conclude
      that shared multisensory experiences might represent one key way to improve our
      ability to resonate with others by overcoming the boundaries between ingroup and
      outgroup categories. 

PMID- 24302901
TI  - On the debated role of temporo-parietal dysfunction in patients with basal
      ganglia neglect.

PMID- 24302902
TI  - Neural dynamics of inflectional and derivational processing in spoken word
      comprehension: laterality and automaticity.
AB  - Rapid and automatic processing of grammatical complexity is argued to take place
      during speech comprehension, engaging a left-lateralized fronto-temporal language
      network. Here we address how neural activity in these regions is modulated by the
      grammatical properties of spoken words. We used combined magneto- and
      electroencephalography to delineate the spatiotemporal patterns of activity that
      support the recognition of morphologically complex words in English with
      inflectional (-s) and derivational (-er) affixes (e.g., bakes, baker). The
      mismatch negativity, an index of linguistic memory traces elicited in a passive
      listening paradigm, was used to examine the neural dynamics elicited by
      morphologically complex words. Results revealed an initial peak 130-180 ms after
      the deviation point with a major source in left superior temporal cortex. The
      localization of this early activation showed a sensitivity to two grammatical
      properties of the stimuli: (1) the presence of morphological complexity, with
      affixed words showing increased left-laterality compared to non-affixed words;
      and (2) the grammatical category, with affixed verbs showing greater left
      lateralization in inferior frontal gyrus compared to affixed nouns (bakes vs.
      beaks). This automatic brain response was additionally sensitive to semantic
      coherence (the meaning of the stem vs. the meaning of the whole form) in left
      middle temporal cortex. These results demonstrate that the spatiotemporal pattern
      of neural activity in spoken word processing is modulated by the presence of
      morphological structure, predominantly engaging the left-hemisphere's fronto
      temporal language network, and does not require focused attention on the
      linguistic input. 

PMID- 24302903
TI  - Time-frequency analysis of short-lasting modulation of EEG induced by TMS during
      wake, sleep deprivation and sleep.
AB  - The occurrence of dynamic changes in spontaneous electroencephalogram (EEG)
      rhythms in the awake state or sleep is highly variable. These rhythms can be
      externally modulated during transcranial magnetic stimulation (TMS) with a
      perturbation method to trigger oscillatory brain activity. EEG-TMS co
      registration was performed during standard wake, during wake after sleep
      deprivation and in sleep in six healthy subjects. Dynamic changes in the regional
      neural oscillatory activity of the cortical areas were characterized using time
      frequency analysis based on the wavelet method, and the modulation of induced
      oscillations were related to different vigilance states. A reciprocal
      synchronizing/desynchronizing effect on slow and fast oscillatory activity was
      observed in response to focal TMS after sleep deprivation and sleep. We observed
      a sleep-related slight desynchronization of alpha mainly over the frontal areas,
      and a widespread increase in theta synchronization. These findings could be
      interpreted as proof of the interference external brain stimulation can exert on
      the cortex, and how this could be modulated by the vigilance state. Potential
      clinical applications may include evaluation of hyperexcitable states such as
      epilepsy or disturbed states of consciousness such as minimal consciousness. 

PMID- 24302904
TI  - NIRS as a tool for assaying emotional function in the prefrontal cortex.
AB  - Despite having relatively poor spatial and temporal resolution, near-infrared
      spectroscopy (NIRS) has several methodological advantages compared with other non
      invasive measurements of neural activation. For instance, the unique
      characteristics of NIRS give it potential as a tool for investigating the role of
      the prefrontal cortex (PFC) in emotion processing. However, there are several
      obstacles in the application of NIRS to emotion research. In this mini-review, we
      discuss the findings of studies that used NIRS to assess the effects of PFC
      activation on emotion. Specifically, we address the methodological challenges of
      NIRS measurement with respect to the field of emotion research, and consider
      potential strategies for mitigating these problems. In addition, we show that two
      fields of research, investigating (i) biological predisposition influencing PFC
      responses to emotional stimuli and (ii) neural mechanisms underlying the bi
      directional interaction between emotion and action, have much to gain from the
      use of NIRS. With the present article, we aim to lay the foundation for the
      application of NIRS to the above-mentioned fields of emotion research. 

PMID- 24302905
TI  - The comparison between motor imagery and verbal rehearsal on the learning of
      sequential movements.
AB  - Mental practice refers to the cognitive rehearsal of a physical activity. It is
      widely used by athletes to enhance their performance and its efficiency to help
      train motor function in people with physical disabilities is now recognized.
      Mental practice is generally based on motor imagery (MI), i.e., the conscious
      simulation of a movement without its actual execution. It may also be based on
      verbal rehearsal (VR), i.e., the silent rehearsal of the labels associated with
      an action. In this study, the effect of MI training or VR on the learning and
      retention of a foot-sequence task was investigated. Thirty right-footed subjects,
      aged between 22 and 37 years old (mean: 27.4 +/- 4.1 years) and randomly assigned
      to one of three groups, practiced a serial reaction time task involving a
      sequence of three dorsiflexions and three plantar flexions with the left foot.
      One group (n = 10) mentally practiced the sequence with MI for 5 weeks, another
      group (n = 10) mentally practiced the sequence with VR of the foot positions for
      the same duration, and a control group (n = 10) did not practice the sequence
      mentally. The time to perform the practiced sequence as well as an unpracticed
      sequence was recorded before training, immediately after training and 6 months
      after training (retention). The main results showed that the speed improvement
      after training was significantly greater in the MI group compared to the control
      group and tended to be greater in the VR group compared to the control group. The
      improvement in performance did not differ in the MI and VR groups. At retention,
      however, no difference in response times was found among the three groups,
      indicating that the effect of mental practice did not last over a long period
      without training. Interestingly, this pattern of results was similar for the
      practiced and non-practiced sequence. Overall, these results suggest that both MI
      training and VR help to improve motor performance and that mental practice may
      induce non-specific effects. 

PMID- 24302906
TI  - Early detection of microstructural white matter changes associated with arterial
      pulsatility.
AB  - Increased cerebral blood flow pulsatility is common in vascular dementia and is
      associated with macrostructural damage to cerebral white matter or leukoaraiosis
      (LA). In this study, we examine whether cerebral blood flow pulsatility is
      associated with macrostructural and microstructural changes in cerebral white
      matter in older adults with no or mild LA and no evidence of dementia. Diffusion
      Tensor Imaging was used to measure fractional anisotropy (FA), an index of the
      microstructural integrity of white matter, and radial diffusivity (RaD), a
      measure sensitive to the integrity of myelin. When controlling for age, increased
      arterial pulsation was associated with deterioration in both measures of white
      matter microstructure but not LA severity. A stepwise multiple linear regression
      model revealed that arterial pulsatility index was the strongest predictor of FA
      (R = 0.483, adjusted R (2) = 0.220), followed by LA severity, but not age. These
      findings suggest that arterial pulsatility may provide insight into age-related
      reduction in white matter FA. Specifically, increased arterial pulsatility may
      increase perivascular shear stress and lead to accumulation of damage to
      perivascular oligodendrocytes, resulting in microstructural changes in white
      matter and contributing to proliferation of LA over time. Changes in cerebral
      blood flow pulsatility may therefore provide a sensitive index of white matter
      health that could facilitate the early detection of risk for perivascular white
      matter damage and the assessment of the effectiveness of preventative treatment
      targeted at reducing pulsatility. 

PMID- 24302907
TI  - The social emotional developmental and cognitive neuroscience of socioeconomic
      gradients: laboratory, population, cross-cultural and community developmental
      approaches.

PMID- 24302908
TI  - Current perspectives on the mechanisms of auditory hallucinations: introduction
      to the special research topic.

PMID- 24302909
TI  - Delayed depolarization and firing behavior of human motoneurons during voluntary
      muscle contractions.

PMID- 24302910
TI  - Visual motion integration is mediated by directional ambiguities in local motion
      signals.
AB  - The output of primary visual cortex (V1) is a piecemeal representation of the
      visual scene and the response of any one cell cannot unambiguously guide
      sensorimotor behavior. It remains unsolved how subsequent stages of cortical
      processing combine ("pool") these early visual signals into a coherent
      representation. We (Webb et al., 2007, 2011) have shown that responses of human
      observers on a pooling task employing broadband, random dot motion can be
      accurately predicted by decoding the maximum likelihood direction from a
      population of motion-sensitive neurons. Whereas Amano et al. (2009) found that
      the vector average velocity of arrays of narrowband, two-dimensional (2-d) plaids
      predicts perceived global motion. To reconcile these different results, we
      designed two experiments in which we used 2-d noise textures moving behind
      spatially distributed apertures and measured the point of subjective equality
      between pairs of global noise textures. Textures in the standard stimulus moved
      rigidly in the same direction, whereas their directions in the comparison
      stimulus were sampled from a set of probability distributions. Human observers
      judged which noise texture had a more clockwise (CW) global direction. In
      agreement with Amano and colleagues, observers' perceived global motion coincided
      with the vector average stimulus direction. To test if directional ambiguities in
      local motion signals governed perceived global direction, we manipulated the
      fidelity of the texture motion within each aperture. A proportion of the
      apertures contained texture that underwent rigid translation and the remainder
      contained dynamic (temporally uncorrelated) noise to create locally ambiguous
      motion. Perceived global motion matched the vector average when the majority of
      apertures contained rigid motion, but with increasing levels of dynamic noise
      shifted toward the maximum likelihood direction. A class of population decoders
      utilizing power-law non-linearities can accommodate this flexible pooling. 

PMID- 24302911
TI  - Robust multi-site MR data processing: iterative optimization of bias correction,
      tissue classification, and registration.
AB  - A robust multi-modal tool, for automated registration, bias correction, and
      tissue classification, has been implemented for large-scale heterogeneous multi
      site longitudinal MR data analysis. This work focused on improving the an
      iterative optimization framework between bias-correction, registration, and
      tissue classification inspired from previous work. The primary contributions are
      robustness improvements from incorporation of following four elements: (1)
      utilize multi-modal and repeated scans, (2) incorporate high-deformable
      registration, (3) use extended set of tissue definitions, and (4) use of multi
      modal aware intensity-context priors. The benefits of these enhancements were
      investigated by a series of experiments with both simulated brain data set
      (BrainWeb) and by applying to highly-heterogeneous data from a 32 site imaging
      study with quality assessments through the expert visual inspection. The
      implementation of this tool is tailored for, but not limited to, large-scale data
      processing with great data variation with a flexible interface. In this paper, we
      describe enhancements to a joint registration, bias correction, and the tissue
      classification, that improve the generalizability and robustness for processing
      multi-modal longitudinal MR scans collected at multi-sites. The tool was
      evaluated by using both simulated and simulated and human subject MRI images.
      With these enhancements, the results showed improved robustness for large-scale
      heterogeneous MRI processing. 

PMID- 24302912
TI  - The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the
      human two-pore domain potassium channels TASK-1, TASK-3 and TRESK.
AB  - For a long time, the focus of trigeminal chemoperception has rested almost
      exclusively on TRP channels. However, two-pore domain (K2P) potassium channels
      have recently been identified as targets for substances associated with typical
      trigeminal sensations, such as numbing and tingling. In addition, they have been
      shown to be modulated by several TRP agonists. We investigated whether the
      pungent substances piperine, capsaicin, 6-gingerol and polygodial have an effect
      on human K2P channels. For this purpose, we evaluated the effects of these
      pungent substances on both wild-type and mutant K2P channels by means of two
      electrode voltage-clamp experiments using Xenopus laevis oocytes. All four
      pungent substances were found to inhibit the basal activity of TASK-1 (K2P 3.1),
      TASK-3 (K2P 9.1), and TRESK (K2P 18.1) channels. This inhibitory effect was dose
      dependent and, with the exception of polygodial on TASK-1, fully reversible.
      However, only piperine exhibited an IC50 similar to its reported EC50 on TRP
      channels. Finally, we observed for TASK-3 that mutating H98 to E markedly
      decreased the inhibition induced by piperine, capsaicin, and 6-gingerol, but not
      by polygodial. Our data contribute to the relatively sparse knowledge concerning
      the pharmacology of K2P channels and also raise the question of whether K2P
      channels could be involved in the pungency perception of piperine. 

PMID- 24302913
TI  - Retinal and post-retinal contributions to the quantum efficiency of the human eye
      revealed by electrical neuroimaging.
AB  - The retina is one of the best known quantum detectors with rods able to reliably
      respond to single photons. However, estimates on the number of photons eliciting
      conscious perception, based on signal detection theory, are systematically above
      these values after discounting by retinal losses. One possibility is that there
      is a trade-off between the limited motor resources available to living systems
      and the excellent reliability of the visual photoreceptors. On this view, the
      limits to sensory thresholds are not set by the individual reliability of the
      receptors within each sensory modality (as often assumed) but rather by the
      limited central processing and motor resources available to process the constant
      inflow of sensory information. To investigate this issue, we reproduced the
      classical experiment from Hetch aimed to determine the sensory threshold in human
      vision. We combined a careful physical control of the stimulus parameters with
      high temporal/spatial resolution recordings of EEG signals and behavioral
      variables over a relatively large sample of subjects (12). Contrarily to the idea
      that the limits to visual sensitivity are fully set by the statistical
      fluctuations in photon absorption on retinal photoreceptors we observed that the
      state of ongoing neural oscillations before any photon impinges the retina helps
      to determine if the responses of photoreceptors have access to central conscious
      processing. Our results suggest that motivational and attentional off-retinal
      mechanisms play a major role in reducing the QE efficiency of the human visual
      system when compared to the efficiency of isolated retinal photoreceptors. Yet,
      this mechanism might subserve adaptive behavior by enhancing the overall
      multisensory efficiency of the whole system composed by diverse reliable sensory
      modalities. 

PMID- 24302914
TI  - The multiple pathways by which self-control predicts behavior.

PMID- 24302915
TI  - Impact of cognitive and linguistic ability on gaze behavior in children with
      hearing impairment.
AB  - In order to explore verbal-nonverbal integration, we investigated the influence
      of cognitive and linguistic ability on gaze behavior during spoken language
      conversation between children with mild-to-moderate hearing impairment (HI) and
      normal-hearing (NH) peers. Ten HI-NH and 10 NH-NH dyads performed a referential
      communication task requiring description of faces. During task performance, eye
      movements and speech were tracked. Cox proportional hazards regression was used
      to model associations between performance on cognitive and linguistic tasks and
      the probability of gaze to the conversational partner's face. Analyses compare
      the listeners in each dyad (HI: n = 10, mean age = 12; 6 years, SD = 2; 0, mean
      better ear pure-tone average 33.0 dB HL, SD = 7.8; NH: n = 10, mean age = 13; 7
      years, SD = 1; 11). Group differences in gaze behavior - with HI gazing more to
      the conversational partner than NH - remained significant despite adjustment for
      ability on receptive grammar, expressive vocabulary, and complex working memory.
      Adjustment for phonological short term memory, as measured by non-word
      repetition, removed group differences, revealing an interaction between group
      membership and non-word repetition ability. Stratified analysis showed a twofold
      increase of the probability of gaze-to-partner for HI with low phonological short
      term memory capacity, and a decreased probability for HI with high capacity, as
      compared to NH peers. The results revealed differences in gaze behavior
      attributable to performance on a phonological short term memory task.
      Participants with HI and low phonological short term memory capacity showed a
      doubled probability of gaze to the conversational partner, indicative of a visual
      bias. The results stress the need to look beyond the HI in diagnostics and
      intervention. Acknowledgment of the finding requires clinical assessment of
      children with HI to be supported by tasks tapping phonological processing. 

PMID- 24302916
TI  - Determinants of attentional modulation near the hands.
AB  - A series of visual search experiments conducted by Abrams et al. (2008) indicates
      that disengagement of visual attention is slowed when the array of objects that
      are to be searched are close to the hands (hands on the monitor) than if they are
      not close to the hands (hands in the lap). These experiments establish the impact
      one's hands can have on visual attentional processing. In the current paper we
      more closely examine these two hand postures with the goal of pinpointing which
      characteristics are crucial for the observed differences in attentional
      processing. Specifically, in a set of 4 experiments we investigated additional
      hand postures and additional modes of response to address this goal. We
      replicated the original Abrams et al. (2008) effect when only the two original
      postures were used; however, surprisingly, the effect was extinguished with the
      new range of postures and response modes, and this extinction persisted across
      different populations (German and English students), and different experimental
      hardware. Furthermore, analyses indicated that it is unlikely that the extinction
      of the effect was caused by increased practice due to additional blocks of trials
      or by an increased probability that participants were able to guess the purpose
      of the experiment. As such our results suggest that in addition to the nature of
      the postures of the hand, the number of postures is a further important factor
      that influences the impact the hands have on visual processing. 

PMID- 24302917
TI  - The primacy of cognition in the manifestations of substance use disorders.

PMID- 24302918
TI  - Evidence That the Blood Biomarker SNTF Predicts Brain Imaging Changes and
      Persistent Cognitive Dysfunction in Mild TBI Patients.
AB  - Although mild traumatic brain injury (mTBI), or concussion, is not typically
      associated with abnormalities on computed tomography (CT), it nevertheless causes
      persistent cognitive dysfunction for many patients. Consequently, new prognostic
      methods for mTBI are needed to identify at risk cases, especially at an early and
      potentially treatable stage. Here, we quantified plasma levels of the
      neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment
      (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and
      normal uninjured controls (UCs) (age range 12-30 years), and compared them with
      findings from diffusion tensor imaging (DTI) and long-term cognitive assessment.
      SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI
      cases and in 3 of 13 OI cases, but in none of the UCs. An elevation in plasma
      SNTF corresponded with significant differences in fractional anisotropy and the
      apparent diffusion coefficient in the corpus callosum and uncinate fasciculus
      measured by DTI. Furthermore, increased plasma SNTF on the day of injury
      correlated significantly with cognitive impairment that persisted for at least 3
      months, both across all study participants and also among the mTBI cases by
      themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied
      by corresponding white matter and cognitive abnormalities, raises the possibility
      of identifying undiagnosed cases of mTBI. These data suggest that the blood level
      of SNTF on the day of a CT-negative mTBI may identify a subset of patients at
      risk of white matter damage and persistent disability. SNTF could have prognostic
      and diagnostic utilities in the assessment and treatment of mTBI. 

PMID- 24302919
TI  - Sandy lake health and diabetes project: a community-based intervention targeting
      type 2 diabetes and its risk factors in a first nations community.
AB  - The Sandy Lake Health and Diabetes Project (SLHDP) was initiated in 1991 as a
      partnership between Sandy Lake First Nation and researchers interested in
      addressing the high rates of type 2 diabetes mellitus (T2DM) in the community.
      Following the expressed wishes of the community, the SLHDP has encompassed a
      variety of community-wide interventions and activities including: community
      surveys to document T2DM prevalence and risk factors, the Northern Store program
      aimed at increasing the availability and knowledge of healthy food options, a
      home visit program for the prevention and management of T2DM, a local diabetes
      radio show, a school diabetes curriculum for grades 3 and 4, a community-wide
      walking trail to encourage increased physical activity, youth diabetes summer
      camps, and a variety of community events focusing on nutrition and physical
      activity. Over the 22 year existence of the SLHDP, the community has taken
      ownership of the program and activities have evolved in alignment with community
      needs and priorities. This paper discusses the history, implementation,
      evaluation, and outcomes of the SLHDP and describes its sustainability. The SLHDP
      is a model of culturally appropriate participatory research that is iterative,
      with reciprocal capacity building for both key community stakeholders and
      academic partners. 

PMID- 24302920
TI  - Quantitative analysis of neurotransmitter pathways under steady state conditions 
      a perspective.
AB  - In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti
      carried out a mathematical analysis of neurotransmitter pathways in brain,
      modeling compartmental nitrogen flux among several major participants - ammonia,
      glutamine, glutamate, GABA, and selected amino acids. This analysis is important
      because cerebral nitrogen metabolism is perturbed in many diseases, including
      liver disease and inborn errors of the urea cycle. These diseases result in an
      elevation of blood ammonia, which is neurotoxic. Here, a brief description is
      provided of the discovery of cerebral metabolic compartmentation of nitrogen
      metabolism - a key feature of cerebral glutamate-glutamine and GABA-glutamine
      cycles. The work of Somersalo and Calvetti is discussed as a model for future
      studies of normal and pathological cerebral ammonia metabolism. 

PMID- 24302921
TI  - Extracellular proteolytic enzymes produced by human pathogenic vibrio species.
AB  - Bacteria in the genus Vibrio produce extracellular proteolytic enzymes to obtain
      nutrients via digestion of various protein substrates. However, the enzymes
      secreted by human pathogenic species have been documented to modulate the
      bacterial virulence. Several species including Vibrio cholerae and V. vulnificus
      are known to produce thermolysin-like metalloproteases termed vibriolysin. The
      vibriolysin from V. vulnificus, a causative agent of serious systemic infection,
      is a major toxic factor eliciting the secondary skin damage characterized by
      formation of the hemorrhagic brae. The vibriolysin from intestinal pathogens may
      play indirect roles in pathogenicity because it can activate protein toxins and
      hemagglutinin by the limited proteolysis and can affect the bacterial attachment
      to or detachment from the intestinal surface by degradation of the mucus layer.
      Two species causing wound infections, V. alginolyticus and V. parahaemolyticus,
      produce another metalloproteases so-called collagenases. Although the detailed
      pathological roles have not been studied, the collagenase is potent to accelerate
      the bacterial dissemination through digestion of the protein components of the
      extracellular matrix. Some species produce cymotrypsin-like serine proteases,
      which may also affect the bacterial virulence potential. The intestinal pathogens
      produce sufficient amounts of the metalloprotease at the small intestinal
      temperature; however, the metalloprotease production by extra-intestinal
      pathogens is much higher around the body surface temperature. On the other hand,
      the serine protease is expressed only in the absence of the metalloprotease. 

PMID- 24302922
TI  - Erratum: Genomic analysis of ERVWE2 locus in patients with Multiple sclerosis:
      absence of genetic association but potential role of Human Endogenous retrovirus
      type W elements in molecular mimicry with myelin antigen.
AB  - [This corrects the article on p. 172 in vol. 4, PMID: 23805135.].

PMID- 24302923
TI  - Late steps in secretory lysosome exocytosis in cytotoxic lymphocytes.
AB  - Natural Killer cells are a subset of cytotoxic lymphocytes that are important in
      host defense against infections and transformed cells. They exert this function
      through recognition of target cells by cell surface receptors, which triggers a
      signaling program that results in a re-orientation of the microtubule organizing
      center and secretory lysosomes toward the target cell. Upon movement of secretory
      lysosomes to the plasma membrane and subsequent fusion, toxic proteins are
      released by secretory lysosomes in the immunological synapse which then enter and
      kill the target cell. In this minireview we highlight recent progress in our
      knowledge of late steps in this specialized secretion pathway and address
      important open questions. 

PMID- 24302925
TI  - Dendritic cell vaccination, immune regulation, and clinical outcomes in ovarian
      cancer.
AB  - Clinical optimism for dendritic cell vaccination against ovarian cancer has been
      tempered by the knowledge that tumors avail themselves of multiple mechanisms of
      immune evasion, thus blunting the efficacy of therapeutic vaccination. Mechanisms
      of immune suppression include infiltration by regulatory T cells (Treg) and
      myeloid suppressor cell populations, expression of co-inhibitory receptors, and
      expression of indoleamine 2,3-dioxygenase (IDO). Expression of both B7-H1 and IDO
      are associated with differentiation and recruitment of Treg, and clinical studies
      have shown that each of these mechanisms correlates independently with increased
      morbidity and mortality in ovarian cancer patients. In sharp contrast, recent
      studies have indicated that Th17 cell infiltration in ovarian cancer correlates
      with improved patient outcomes and prolonged overall survival. Given that IDO
      plays a pivotal role in the balance between Treg and Th17 immunity, elucidation
      of the mechanisms that regulate IDO activity and immune suppression may lead to
      novel adjuvants to boost the clinical efficacy of dendritic cell vaccination
      against ovarian cancer and other malignancies. 

PMID- 24302924
TI  - Mechanisms Underlying CD4+ Treg Immune Regulation in the Adult: From Experiments
      to Models.
AB  - To maintain immunological balance the organism has to be tolerant to self while
      remaining competent to mount an effective immune response against third-party
      antigens. An important mechanism of this immune regulation involves the action of
      regulatory T-cell (Tregs). In this mini-review, we discuss some of the known and
      proposed mechanisms by which Tregs exert their influence in the context of immune
      regulation, and the contribution of mathematical modeling for these mechanistic
      studies. These models explore the mechanisms of action of regulatory T cells, and
      include hypotheses of multiple signals, delivered through simultaneous antigen
      presenting cell (APC) conjugation; interaction of feedback loops between APC,
      Tregs, and effector cells; or production of specific cytokines that act on
      effector cells. As the field matures, and competing models are winnowed out, it
      is likely that we will be able to quantify how tolerance-inducing strategies,
      such as CD4-blockade, affect T-cell dynamics and what mechanisms explain the
      observed behavior of T-cell based tolerance. 

PMID- 24302926
TI  - Regulation of immune system cell functions by protein kinase C.

PMID- 24302928
TI  - A neuro-fuzzy approach in the classification of students' academic performance.
AB  - Classifying the student academic performance with high accuracy facilitates
      admission decisions and enhances educational services at educational
      institutions. The purpose of this paper is to present a neuro-fuzzy approach for
      classifying students into different groups. The neuro-fuzzy classifier used
      previous exam results and other related factors as input variables and labeled
      students based on their expected academic performance. The results showed that
      the proposed approach achieved a high accuracy. The results were also compared
      with those obtained from other well-known classification approaches, including
      support vector machine, Naive Bayes, neural network, and decision tree
      approaches. The comparative analysis indicated that the neuro-fuzzy approach
      performed better than the others. It is expected that this work may be used to
      support student admission procedures and to strengthen the services of
      educational institutions. 

PMID- 24302929
TI  - Common spatio-time-frequency patterns for motor imagery-based brain machine
      interfaces.
AB  - For efficient decoding of brain activities in analyzing brain function with an
      application to brain machine interfacing (BMI), we address a problem of how to
      determine spatial weights (spatial patterns), bandpass filters (frequency
      patterns), and time windows (time patterns) by utilizing electroencephalogram
      (EEG) recordings. To find these parameters, we develop a data-driven criterion
      that is a natural extension of the so-called common spatial patterns (CSP) that
      are known to be effective features in BMI. We show that the proposed criterion
      can be optimized by an alternating procedure to achieve fast convergence.
      Experiments demonstrate that the proposed method can effectively extract
      discriminative features for a motor imagery-based BMI. 

PMID- 24302927
TI  - Targeting toll-like receptors: promising therapeutic strategies for the
      management of sepsis-associated pathology and infectious diseases.
AB  - Toll-like receptors (TLRs) are pattern recognition receptors playing a
      fundamental role in sensing microbial invasion and initiating innate and adaptive
      immune responses. TLRs are also triggered by danger signals released by injured
      or stressed cells during sepsis. Here we focus on studies developing TLR agonists
      and antagonists for the treatment of infectious diseases and sepsis. Positioned
      at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram
      negative bacteria, TLR2 is involved in the recognition of a large panel of
      microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8,
      TLR9 are specialized in the sensing of nucleic acids produced notably during
      viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis
      drugs, and antagonistic compounds have shown efficient protection from septic
      shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4
      and anti-TLR2 approaches are presented, discussing the challenges of study design
      in sepsis and future exploitation of these agents in infectious diseases. We also
      report results from studies suggesting that the TLR5 agonist flagellin may
      protect from infections of the gastrointestinal tract and that agonists of
      endosomal TLRs are very promising for treating chronic viral infections.
      Altogether, TLR-targeted therapies have a strong potential for prevention and
      intervention in infectious diseases, notably sepsis. 

PMID- 24302930
TI  - A functional model of sensemaking in a neurocognitive architecture.
AB  - Sensemaking is the active process of constructing a meaningful representation
      (i.e., making sense) of some complex aspect of the world. In relation to
      intelligence analysis, sensemaking is the act of finding and interpreting
      relevant facts amongst the sea of incoming reports, images, and intelligence. We
      present a cognitive model of core information-foraging and hypothesis-updating
      sensemaking processes applied to complex spatial probability estimation and
      decision-making tasks. While the model was developed in a hybrid symbolic
      statistical cognitive architecture, its correspondence to neural frameworks in
      terms of both structure and mechanisms provided a direct bridge between rational
      and neural levels of description. Compared against data from two participant
      groups, the model correctly predicted both the presence and degree of four
      biases: confirmation, anchoring and adjustment, representativeness, and
      probability matching. It also favorably predicted human performance in generating
      probability distributions across categories, assigning resources based on these
      distributions, and selecting relevant features given a prior probability
      distribution. This model provides a constrained theoretical framework describing
      cognitive biases as arising from three interacting factors: the structure of the
      task environment, the mechanisms and limitations of the cognitive architecture,
      and the use of strategies to adapt to the dual constraints of cognition and the
      environment. 

PMID- 24302931
TI  - Importance of the ultrasonography in diagnosis of ileal duplication cyst.
AB  - Gastrointestinal duplication cysts are rare congenital anomalies that can be seen
      in anywhere of the gastrointestinal system from the mouth to the anus. These are
      prenatally diagnosed through antenatal ultrasonography. However, attention must
      be paid since these formations might be confused with ovarian or mesenteric
      cysts. Our patient, who had been diagnosed with ovarian cyst on the
      ultrasonography performed in another center and with mesenteric cyst based on the
      abdominal MRI carried out at fifth month of life, presented to our clinic with
      the only complaint of constipation at 9th month of life. The diagnosis was set
      through double wall appearance of duplication cyst on the abdominal
      ultrasonography. The patient's cyst was resected. 

PMID- 24302932
TI  - Bile Duct Strictures Caused by Solid Masses: MR in Differential Diagnosis and as
      a Prognostic Tool to Plan the Endoscopic Treatment.
AB  - The aim of the study was to assess how realiable is differential diagnosis and
      prognosis for endoscopic treatment with MR signal characteristics as the
      qualitative parameter and magnetic resonance cholangiopancreatography (MRCP)
      images in cases of bile duct obstructions caused by solid masses. Material and
      Methods. Retrospective study of MR and MRCP images in 80 patients (mean age 58
      ys) was conducted. Mean signal intensity ratio (SIR) from planar MR images and
      MRCP linear measurements were compared between benign and malignant lesions and
      in groups including the size and number of stents placed during ERCP (< 10 F <)
      in 51 cases in which ERCP was performed. Results. Significantly higher SIR values
      were encountered in malignant lesions in T2W images (r = 0,0003) and STIR T2W
      images (r = 0,0002). Malignant lesions were characterised by longer strictures (r
      = 0,0071) and greater proximal biliary duct dilatation (r = 0,0024). High
      significance for predicting ERCP conditions was found with mean SIR in STIR T2W
      images and stricture length. Conclusion. Probability of malignancy of solid
      lesions obstructing biliary duct increased with higher SIR in T2W images and with
      longer strictures. Passing the stricture during ERCP treatment was easier and
      more probable in cases of shorter strictures caused by lesions with higher SIR in
      STIR T2W images. 

PMID- 24302933
TI  - The effect of active transport, transport systems, and urban design on population
      health.

PMID- 24302934
TI  - Comparison of cardiovascular risk factors and biochemical profile in patients
      with cardiac syndrome X and obstructive coronary artery disease: A propensity
      score-matched study.
AB  - BACKGROUND: This study was designed to compare the frequency of conventional
      cardiovascular disease risk factors and clinical biochemistry profile in patients
      with cardiac syndrome X (CSX) and obstructive coronary artery disease (CAD).
      METHODS: A cross-sectional study was conducted on patients with typical angina
      and positive exercise tolerance test undergoing coronary angiography in our
      center. 342 consecutive patients with CSX were enrolled into this study and were
      matched regarding age and sex with 342 patients with acute coronary syndrome
      (ACS) and also 342 patients with chronic stable angina (SA). Cardiovascular risk
      factors as well as biochemistry profile of the patients were recorded. RESULTS:
      Mean age of the studied patients was 53.0 years and 41.5% were male. There was no
      significant difference between the CSX patients and CAD patients regarding body
      mass index (BMI). Frequency of diabetes mellitus, hyperlipidemia, smoking, family
      history of premature CAD and hypertension was significantly lower in patients
      with CSX than ACS and SA patients. Patients with CSX had significantly higher
      levels of high-density lipoprotein cholesterol (HDL-cholesterol) than comparators
      while the levels of low-density lipoprotein cholesterol (LDL-cholesterol), total
      cholesterol, triglyceride and fasting blood sugar (FBS) were significantly lower
      in patients with CSX than CAD patients. CONCLUSION: The present study
      demonstrated that CSX patients had substantially lower frequency of all
      conventional CVD risk factors than patients with obstructive CAD. This might aid
      in developing novel scoring systems or appropriateness criteria for angiographic
      evaluation of patients with typical angina and positive exercise test in order to
      reduce the rate of negative results.

PMID- 24302935
TI  - Risk of sudden cardiac death.
AB  - BACKGROUND: The aim of this study was to determine characteristics of patients
      with sudden cardiac arrest (SCA) and/or sudden cardiac death (SCD). We need an
      effective risk stratification method for SCD in patients without low left
      ventricular ejection fraction (LVEF). METHODS: The study population of this cross
      sectional study consisted of 241 patients with SCA or SCD who were admitted to an
      academic hospital, in Tehran, Iran, from 2011 through 2012. SCD was defined as
      unexpected death from cardiac causes, heralded by abrupt loss of consciousness
      within one hour of the onset of acute changes in cardiovascular status, or an
      unobserved death in which the patient was seen and known to be doing well within
      the previous 24 hours. Survivors of aborted SCD were also included in the study.
      Clinical and paraclinical characteristics as well as emergency department
      complications of patients were recorded. RESULTS: The mean age of population was
      66.0 +/- 16.5 (17 to 90 years). Among the patients, 166 (68.9 %) were male, 50
      (20.7%) were smoker, 77 (32.0%) had hypertension, 47 (19.5%) had diabetes
      mellitus, 21 (8.7%) had hyperlipidemia, and 32 (13.3%) had renal insufficiency.
      According to New York Health Association (NYHA) functional class, 31 (12.9%)
      patients were asymptomatic, 42 (17.4) and 99 (41.1%) subjects were in NYHA I and
      II, respectively and only 69 (28.6%) patients were in NYHA III or IV. In this
      study, presenting arrhythmia was pulseless electrical activity or asystole which
      was observed in 130 (53.9%) subjects. Ventricular tachycardia (VT) or ventricular
      fibrillation (VF) was seen in 53 (22%) patients. Cardiopulmonary resuscitation in
      emergency room was successful only in 46 (19.1%) subjects. CONCLUSION: Low
      ejection fraction (EF) may be an independent predictor of sudden cardiac death in
      patients, but it is not enough. While implantable cardioverter defibrillators can
      save lives, we are lacking effective risk stratification and prevention methods
      for the majority of patients without low EF who will experience SCD.

PMID- 24302936
TI  - Preventive effect of cinnamon essential oil on lipid oxidation of vegetable oil.
AB  - BACKGROUND: Lipid oxidation is the main deterioration process that occurs in
      vegetable oils. This process was effectively prevented by natural antioxidants.
      Cinnamomum zeylanicum (Cinnamon) is rich with antioxidants. The present study was
      conducted to evaluate the effect of cinnamon on malondialdehyde (MDA) rate
      production in two high consumption oils in Iranian market. METHODS: Chemical
      composition of cinnamon essential oil was analyzed by gas chromatography-mass
      spectroscopy (GC-MS). 200 ul each oil, 50 ul tween 20, and 2 ml of 40 Mm AAPH
      solutions were mixed and the prepared solution was divided into four glass vials.
      Respectively, 50 ul of 500, 1000 and 2000 ppm of cinnamon essential oil were
      added to three glass vials separately and one of the glass vials was used as the
      control. All of the glass vials were incubated at 37 degrees  C water bath. Rate
      of MDA production was measured by thiobarbituric acid (TBA) test at the baseline
      and after the 0.5, 1, 2, 3 and 5 hours. RESULTS: Compounds of cinnamon essential
      oil by GC-MS analysis such as cinnamaldehyde (96.8%), alpha-capaene (0.2%), alpha
      murolene (0.11%), para-methoxycinnamaldehyde (0.6%) and delta-cadinen (0.4%) were
      found to be the major compounds. For both oils, maximum rate of MDA production
      was achieved in 5th hours of heating. Every three concentrations of cinnamon
      essential oil significantly decreased MDA production (P < 0.05) in comparison
      with the control. CONCLUSION: Essential oil of cinnamon considerably inhibited
      MDA production in studied oils and can be used with fresh and heated oils for
      reduction of lipid peroxidation and adverse free radicals effects on body.

PMID- 24302937
TI  - Evaluating the relative frequency and predicting factors of acute renal failure
      following coronary artery bypass grafting.
AB  - BACKGROUND: Renal dysfunction or acute renal failure in patients undergoing
      coronary artery bypass grafting (CABG) is an important cause of morbidity and
      mortality. The great impact of acute renal failure (ARF) in the outcomes of
      cardiac surgery demands its study in our population, encouraging to the
      elaboration of this study, which aimed to identify the incidence and risk factors
      of ARF after CABG. METHODS: Since March 2010 to 2011, 589 patients were studied
      who underwent CABG in Sina Hospital (Isfahan, Iran). In this cross-sectional
      study, patients were divided into two groups based on the occurrence of ARF after
      CABG and measured variables were compared between the two groups was also
      statistically significant. P value less than 0.05 was set as a significant level.
      RESULTS: A total of 434 men and 155 women were enrolled in the study. The mean
      age of the study subjects was 57.6 years. ARF was seen in about 22% of patients
      after CABG. The mean age of ARF group was more than 3 years higher than that in
      the other group and the difference was significant between the two groups. Serum
      creatinine level after the surgery was different between the two groups.
      Moreover, the history of diabetes mellitus was significantly different between
      the two groups. Pump time comparison also showed was also statistically
      significant. CONCLUSION: Our data showed older patients were more prone to
      affected by ARF. In addition, diabetic patients should be considered as high risk
      patients and are more likely to deteriorate by ARF. Despite increased prevalence
      of renal insufficiency in CABG patients, studies show that in most cases, this is
      not a serious problem and it is easily treatable. A lower proportion of patients
      (1.0 to 1.7% in different large series) develop ARF severe enough to require
      dialysis.

PMID- 24302938
TI  - A retrospective cohort study on factors associated blood pressure using
      multilevel modeling.
AB  - BACKGROUND: Hypertension is a health problem in Iran. Given the importance of
      this subject, we reviewed the factors affecting the blood pressure in this
      survey. METHODS: This retrospective cohort study was performed on 3961 male
      workers employed at Isfahan Polyacryl Corporation (Iran) in health and safety
      executive between 1996 until 2008. In this study, systolic and diastolic blood
      pressure (SBP and DBP) were considered as dependent variables; body mass index
      (BMI), age, type of job, marital status, shift work and educational level were
      considered as independent variables. MLwiN programmer version 2.1 was used to
      analyze the data. RESULTS: BMI, age, shift work, marital status and educational
      level had statistical significant association with DBP. The result for SBP was
      similar to DBP except shift work and educational level that had no statistically
      significant association. CONCLUSION: The results can be considered in the
      industry to provide practical solutions to reduce blood pressure.

PMID- 24302939
TI  - Aortic valve streptococcus group B endocarditis post-extracorporeal shock wave
      lithotripsy.
AB  - BACKGROUND: Sub-acute left-sided bacterial endocarditis is a serious condition
      that may present with variable clinical manifestations. Its symptoms include both
      sterile and infected emboli, and various immunological phenomena. CASE REPORT:
      This report presents a 55 year old man with frequency and dysuria after a
      lithotripsy and several admissions with urosepsis. Due to the suspicion of
      infective endocarditis echocardiography was done which confirmed streptococcus
      group B endocarditis. CONCLUSION: Streptococci group B is one of the rare causes
      of infective endocarditis, but it was observed after various producers such as
      lithotripsy.

PMID- 24302940
TI  - A rare anomalous origin of left subclavian artery from the circle of Willis in
      combination with right sided aortic arch: A case report.
AB  - BACKGROUND: One of the rare aortic congenital abnormalities is right sided aortic
      arch which is occurred in approximately 0.1% of the population. The anomalous
      origin of the subclavian arteries has also been reported. CASE REPORT: In this
      study, a case of a right-sided aortic arch with anomalous left subclavian artery
      origin from the cerebral arteries is presented which was diagnosed in Computed
      tomography angiogram (CT angiogram) and angiography of a 10-year-old boy referred
      due to recurrent chest pains during two weeks before admission and pulselessness
      of his left upper limb and left carotid artery. CONCLUSION: Many of the
      congenital vascular anomalies may have no obvious signs or symptoms and therefore
      the exact history and physical examination could help us in better diagnosis.
      Besides, some of these anomalies are associated with other abnormalities of other
      body organs particularly the cardiac system.

PMID- 24302941
TI  - Suggested indications of clinical practice guideline for stem cell-therapy in
      cardiovascular diseases: A stepwise appropriate use criteria for regeneration
      therapy.
AB  - Despite astonishing progress concerning cardiovascular diseases, patients are
      still suffering from complications of acute insults. Due to reverse remodeling
      and improper myocyte rebuilding, heart failure has become a common problem these
      days which needs more powerful myocardial reconstructing strategies. Indeed, no
      option cases afflicted with non-healing peripheral vascular diseases; refractory
      stable and unstable angina is the other field with paucity of proper treatments.
      For these cases, stem cell-based therapies became optimistic treatment, but lack
      of guideline-based indications regarding stem-cell is still a major problem which
      limits application of these cells for such end-stage cases. Here, an outline of
      appropriateness criteria for stem cell-based therapy is suggested. 

PMID- 24302942
TI  - Is psychiatry scientific? A letter to a 21st century psychiatry resident.
AB  - During the development of the DSM-5, even the lay press questioned psychiatr's
      scientific validity. This review provides 21st century psychiatry residents with
      ways of answering these attacks by defining the concepts and history of
      psychiatry (a branch of medicine), medicine and science. Psychiatric language has
      two levels: first, describing symptoms and signs (19th century descriptive
      psychopathology developed in France and Germany), and second, describing
      disorders (psychiatric nosology was developed in the early 20th century by
      Kraepelin and resuscitated by the US neo-Kraepelinian revolution leading to the
      DSM-III). Science is a complex trial-and-error historical process that can be
      threatened by those who believe too much in it and disregard its limitations. The
      most important psychiatric advances, electroconvulsive therapy and major
      psychopharmacological agents, were discovered by "chance", not by scientific
      planning. Jaspers's General Psychopathology is a complex 100-year-old book that
      describes: 1) psychiatric disorders as heterogeneous and 2) psychiatry as a
      hybrid scientific discipline requiring a combination of understanding (a social
      science method) and explanation (a natural science method). In the 21st century
      Berrios reminds us of psychiatry's unfortunate methodological issues due to
      hybrid symptoms and disorders, some of which are better understood as problems in
      communication between interacting human beings; in those situations neuroscience
      methods such as brain imaging make no sense. A new language is needed in
      psychiatry. East Asian psychiatry residents, who are not particularly attached to
      the antiquated language currently used, may be particularly equipped for the task
      of recreating psychiatric language using 21st century knowledge. 

PMID- 24302943
TI  - Bipolar spectrum: a review of the concept and a vision for the future.
AB  - This paper reviews the bipolar spectrum concept historically and empirically. It
      describes how the concept derives from Kraepelin, but was lost with DSM-III,
      which divided the broad manic-depressive illness concept, based on recurrent mood
      episodes of either polarity, to the bipolar versus unipolar dichotomy, based on
      allowing non-recurrent mood episodes of only one polarity. This approach followed
      the views of Karl Leonhard and other critics of Kraepelin. Thus post DSM-III
      American psychiatry is not neo-Kraepelinian, as many claim, but neo-Leonhardian.
      The bipolar spectrum approach, as advocated by Akiskal and Koukopoulos first,
      harkens back to the original broad Kraepelinian view of manic-depressive illness.
      The evidence for and against this approach is discussed, and common
      misconceptions, including mistaken claims that borderline personality is similar,
      are revealed and critiqued. 

PMID- 24302945
TI  - Clinical Usefulness of Loudness Dependence of Auditory Evoked Potentials (LDAEP)
      in Patients with Bipolar Disorder.
AB  - While it has been reported previously that the loudness dependence of auditory
      evoked potentials (LDAEP) is a putative biological marker or a predictor of
      treatment response, there have been few studies of LDAEP in bipolar disorder.
      However, a recent study by Park and colleagues raised the possibility that the
      LDAEP could be useful as a biological marker of bipolar disorder. They found that
      the LDAEP was significantly higher in normal controls than in patients with
      either bipolar disorder or schizophrenia. Lee and colleagues also examined the
      LDAEP in bipolar disorder and normal controls, and found that it differed
      according to the bipolar phase, being significantly higher in cases of euthymic
      bipolar disorder, bipolar depression, and bipolar mania. With regard to treatment
      response, early clinical findings were that a higher LDAEP and a stronger
      intensity dependence of visual evoked potentials were related to a favorable
      response to lithium treatment. Juckel and colleagues recently demonstrated that
      the pretreatment LDAEP could be a predictor of successful prophylactic lithium
      treatment. The present article reviews the literature in order to determine
      whether the LDAEP can be used as a biological marker or a predictor of treatment
      response in patients with bipolar disorder and of manic switch or treatment
      resistance in patients with major depressive episode(s). 

PMID- 24302944
TI  - Circadian rhythm hypotheses of mixed features, antidepressant treatment
      resistance, and manic switching in bipolar disorder.
AB  - Numerous hypotheses have been put forth over the years to explain the development
      of bipolar disorder. Of these, circadian rhythm hypotheses have gained much
      importance of late. While the hypothalamus-pituitary-adrenal (HPA) axis
      hyperactivation hypothesis and the monoamine hypothesis somewhat explain the
      pathogenic mechanism of depression, they do not provide an explanation for the
      development of mania/hypomania. Interestingly, all patients with bipolar disorder
      display significant disruption of circadian rhythms and sleep/wake cycles
      throughout their mood cycles. Indeed, mice carrying the Clock gene mutation
      exhibit an overall behavioral profile that is similar to human mania, including
      hyperactivity, decreased sleep, lowered depression-like behavior, and lower
      anxiety. It was recently reported that monoamine signaling is in fact regulated
      by the circadian system. Thus, circadian rhythm instability, imposed on the
      dysregulation of HPA axis and monoamine system, may in turn increase individual
      susceptibility for switching from depression to mania/hypomania. In addition to
      addressing the pathophysiologic mechanism underlying the manic switch, circadian
      rhythm hypotheses can explain other bipolar disorder-related phenomena such as
      treatment resistant depression and mixed features. 

PMID- 24302946
TI  - Validation of the dementia care assessment packet-instrumental activities of
      daily living.
AB  - OBJECTIVE: We aimed to evaluate the psychometric properties of the IADL measure
      included in the Dementia Care Assessment Packet (DCAP-IADL) in dementia patients.
      METHODS: The study involved 112 dementia patients and 546 controls. The DCAP-IADL
      was scored in two ways: observed score (OS) and predicted score (PS). The
      reliability of the DCAP-IADL was evaluated by testing its internal consistency,
      inter-rater reliability and test-retest reliability. Discriminant validity was
      evaluated by comparing the mean OS and PS between dementia patients and controls
      by ANCOVA. Pearson or Spearman correlation analysis was performed with other
      instruments to assess concurrent validity. Receiver operating characteristics
      curve analysis was performed to examine diagnostic accuracy. RESULTS: Chronbach's
      alpha coefficients of the DCAP-IADL were above 0.7. The values in dementia
      patients were much higher (OS=0.917, PS=0.927), indicating excellent degrees of
      internal consistency. Inter-rater reliabilities and test-retest reliabilities
      were statistically significant (p<0.05). PS exhibited higher reliabilities than
      OS. The mean OS and PS of dementia patients were significantly higher than those
      of the non-demented group after controlling for age, sex and education level. The
      DCAP-IADL was significantly correlated with other IADL instruments and MMSE-KC
      (p<0.001). Areas under the curves of the DCAP-IADL were above 0.9. CONCLUSION:
      The DCAP-IADL is a reliable and valid instrument for evaluating instrumental
      ability of daily living for the elderly, and may also be useful for screening
      dementia. Moreover, administering PS may enable the DCAP-IADL to overcome the
      differences in gender, culture and life style that hinders accurate evaluation of
      the elderly in previous IADL instruments.

PMID- 24302947
TI  - The Relationship between Impulsivity and Quality of Life in Euthymic Patients
      with Bipolar Disorder.
AB  - OBJECTIVE: Bipolar disorder (BD) is characterized by elevated impulsivity, even
      during periods of remission. Many recovered BD patients have functional
      impairments, which can lead to poor quality of life (QoL). The aim of this study
      was to investigate the association between impulsivity and QoL in euthymic BD
      patients. METHODS: A total of 56 remitted or recovered patients with type I or II
      BD, diagnosed based on Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV) criteria, were recruited. Psychiatrists administered the
      Clinical Global Impression (CGI) for BD and the Global Assessment of Functioning
      (GAF) scales and then interviewed the subjects to assess clinical variables.
      Patients completed the Barratt Impulsiveness Scale (BIS-11) and the World Health
      Organization Quality of Life Assessment Instrument-Brief Form (WHOQoL-BREF).
      Pearson correlations, univariate regression analyses, and multiple linear
      regression analyses were performed. RESULTS: The BIS-11 total score was
      significantly correlated with the WHOQoL-BREF total score (r=-0.55, p<0.01) and
      with the WHOQoL-BREF subscales. After controlling for GAF score and other
      clinical variables, the BIS-11 total score (beta=-0.43, p=0.001) was
      independently associated with overall QoL. Additionally, the BIS-11 total score
      was particularly strongly associated with the physical, psychological, and social
      domains of the multi-dimensional QoL scale. CONCLUSION: Our results suggest that
      high impulsivity is related to low QoL in euthymic BD patients. Further studies
      are needed to examine whether interventions for high impulsivity effectively
      improve QoL in patients with BD.

PMID- 24302948
TI  - Nocturnal enuresis is associated with attention deficit hyperactivity disorder
      and conduct problems.
AB  - OBJECTIVE: There are no published prevalence estimates of elimination disorders
      and their association with disruptive-behavior disorders among children in the
      Asian region using standardized diagnostic interviews. This study was conducted
      to determine the prevalence of elimination disorders and its association with
      disruptive-behavior disorders in a representative sample of children in Seoul,
      Korea. METHODS: The diagnosis of enuresis and encopresis was derived from parent
      reported data for "enuresis and encopresis," collected using the Diagnostic
      Interview Schedule for Children, from a representative sample of 6- to 12-year
      old children (n=1,645) who participated in the 2005 Seoul Child and Adolescent
      Mental Health Survey. Prevalence data for attention deficit and disruptive
      behavior disorders were collected from the same sample. RESULTS: The overall 12
      month prevalence of nocturnal enuresis and encopresis was 1.8% and 0.6%,
      respectively. Enuresis and encopresis prevalence in boys was significantly
      greater than that in girls. Enuresis and encopresis was most common at 7 to 9
      years of age. Enuresis was significantly associated with ADHD (OR 2.6, 95% CI 1.0
      6.9) and conduct disorder (CD; OR 4.7, 95% CI 1.0-22.4). CONCLUSION: Enuresis is
      significantly associated with ADHD and CD, so these conditions must be assessed
      together during the evaluation of children with enuresis.

PMID- 24302949
TI  - The impact of personality traits on ratings of obsessive-compulsive symptoms.
AB  - OBJECTIVE: The goal of this study was to evaluate consistencies and discrepancies
      between clinician-administered and self-report versions of the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS) and to examine relationships between these
      scales and personality traits. METHODS: A total of 106 patients with obsessive
      compulsive disorder (OCD) participated in this study. All participants were
      assessed with both clinician-administered and self-report versions of the Y-BOCS.
      The Structured Clinical Interview for DSM-IV Axis II Disorders Personality
      Questionnaire (SCID-II-PQ) was used to evaluate relationships between personality
      traits and scores on the Y-BOCS. RESULTS: Scores on the clinician-administered Y
      BOCS and its obsession subscale were significantly higher than were those on the
      self-report version. However, we found no significant differences in compulsion
      subscale scores. We also found that the discrepancies in the scores on the two
      versions of the Y-BOCS and its compulsion subscale were significantly positively
      correlated with scores for narcissistic personality traits on the SCID-II-PQ.
      Additionally, narcissistic personality traits had a significant effect on the
      discrepancy in the scores on the two versions of the Y-BOCS and its compulsion
      subscale in the multiple linear regression analysis. CONCLUSION: This is the
      first study to elucidate relationships between personality traits and
      discrepancies between scores on the two versions of the Y-BOCS. Although
      clinicians tend to rate obsessive symptoms as being more severe than do patients,
      clinicians may underestimate the degree to which individuals with narcissistic
      personality traits suffer more from subjective discomfort due to compulsive
      symptoms. Therefore, the effect of personality traits on symptom severity should
      be considered in the treatment of OCD.

PMID- 24302950
TI  - Disruption of orbitofronto-striatal functional connectivity underlies maladaptive
      persistent behaviors in alcohol-dependent patients.
AB  - OBJECTIVE: Alcohol dependence is characterized by persistent alcohol-seeking
      despite negative consequences. Previous studies suggest that maladaptive
      persistent behaviors reflect alcohol-induced brain changes that cause alterations
      in the cortico-striatal-limbic circuit. METHODS: Twenty one alcohol dependent
      patients and 24 age-matched healthy controls performed a decision-making task
      during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a
      region-of-interest and performed seed-based functional connectivity analysis.
      RESULTS: Healthy controls were more flexible in adapting an alternative
      behavioral strategy, which correlated with stronger mOFC-dorsal striatum
      functional connectivity. In contrast, alcohol dependent patients persisted to the
      first established behavioral strategy. The mOFC-dorsal striatum functional
      connectivity was impaired in the alcohol-dependent patients, but increased in
      correlation with the duration of abstinence. CONCLUSION: Our findings support
      that the disruption of the mOFC-striatal circuitry contribute to the maldaptive
      persistent behaviors in alcohol dependent patients.

PMID- 24302952
TI  - Decreased serum sulphydryl levels as a sign of increased oxidative stress in
      generalized anxiety disorder.
AB  - OBJECTIVE: In recent years, many published studies have focused on the
      relationship between oxidative stress and psychiatric disorders. However, studies
      in generalized anxiety disorder (GAD) are few despite relatively high prevalence
      rates. In an attempt to fill this gap in the literature we aimed to measure serum
      levels of free sulphydryl, an important member of antioxidant defense mechanisms,
      of the patients with GAD. METHODS: A total of 35 (23 female, 12 male) GAD
      patients without any other co-morbid medical or psychiatric disorder and 35 (23
      female, 12 male) healthy controls have been included in the study. Disease
      severity of the patients were quantified by using the Hamilton Anxiety Rating
      Scale (HAM-A). Serum free sulphydryl group levels of patients and healthy
      controls were measured in an appropriate way. RESULTS: Mean level of serum
      sulphydryl groups was significantly lower in the patient group. There was a
      negative correlation between their level and the disease duration. However, they
      did not show any significant correlation with the disease severity. CONCLUSION:
      Decreased serum sulphydryl level observed in pure GAD patients suggests an
      increased oxidative stress in these patients. Well designed future researches are
      needed to replicate our findings and to test the implications of the present
      study.

PMID- 24302951
TI  - Anti-intrusion effect of Lorazepam: an experimental study.
AB  - OBJECTIVE: Easy triggering of trauma-related episodic memory fragments caused by
      perceptual cues is tied to strong perceptual priming in the implicit memory
      system. And among benzodiazepines, only lorazepam has been consistently reported
      to have an atypical suppression effect on perceptual priming processes. The aim
      of this study was to investigate the effects of single doses of lorazepam,
      diazepam, and a placebo on intrusive memories after exposure to a distressing
      videotape and to explore whether the anti-intrusive effect of lorazepam is
      acquired as a result of the suppression of perceptual but not conceptual priming
      processes. METHODS: Under prospective, randomized, and double-blind conditions,
      we compared the anti-intrusion effect of a single dose of lorazepam (n=22) with
      that of diazepam (n=22) and a placebo (n=21) in young healthy Korean college
      students following exposure to a traumatic videotape. RESULTS: We present the
      first finding for an anti-intrusion effect of lorazepam. One day after the
      medication, lorazepam, rather than diazepam or the placebo, significantly reduced
      the extent of intrusion and data-driven processing of the traumatic information.
      There were no differences among the three conditions in state anxiety,
      depression, and an arousal scale throughout the experiment. CONCLUSION: Results
      from this study suggest the possibility of lorazepam as a candidate anti
      intrusion drug, as well as the cautious use of diazepam in the treatment of PTSD
      patients. The anti-intrusive effect of lorazepam is directly related to its
      atypical inhibitory effect on implicit perceptual priming processes. The present
      study provides support for the enhanced perceptual priming hypothesis of PTSD.

PMID- 24302953
TI  - CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with
      Major Depression.
AB  - OBJECTIVE: Cytochrome P450 (CYP) enzymatic activity, which is influenced by CYP
      genetic polymorphism, is known to affect the inter-individual variation in the
      efficacy and tolerability of antidepressants in major depressive disorder (MDD).
      Escitalopram is metabolized by CYP2D6, and recent studies have reported a
      correlation between clinical outcomes and CYP2D6 genetic polymorphism. The
      purpose of this study was to determine the relationship between the CYP2D6 P34S
      polymorphism (C188T, rs1065852) and the efficacy of escitalopram treatment in
      Korean patients with MDD. METHODS: A total of 94 patients diagnosed with MDD were
      recruited for the study and their symptoms were evaluated using the 21-item
      Hamilton Depression Rating scale (HAMD-21). The association between the CYP2D6
      P34S polymorphism and the clinical outcomes (remission and response) was
      investigated after 1, 2, 4, 8, and 12 weeks of escitalopram treatment using
      multiple logistic regression analysis and chi(2) test. RESULTS: The proportion of
      P allele carriers (PP, PS) in remission status was greater than that of S allele
      homozygotes (SS) after 8 and 12 weeks of escitalopram treatment. Similarly, P
      allele carriers exhibited a greater treatment response after 8 and 12 weeks of
      escitalopram treatment than S allele homozygotes. CONCLUSION: Our results suggest
      that the P allele of the CYP2D6 P34S polymorphism is a favorable factor in
      escitalopram treatment for MDD, and that the CYP2D6 P34S polymorphism may be a
      good genetic marker for predicting escitalopram treatment outcomes.

PMID- 24302954
TI  - Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in
      Patients with Major Depressive Disorder.
AB  - OBJECTIVE: Cytokines are believed to have a role in the pathophysiology of major
      depression. The alteration in levels of pro-inflammatory cytokines [interleukin
      1beta (IL-1beta), IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor
      alpha] in major depression supports the cytokine hypothesis of this illness. IL
      23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on
      their role in major depression. This study investigated the potential role of the
      IL-23 and IL-17 axis in major depression. METHODS: Plasma IL-23 and IL-17 levels
      were measured in 26 major depressive disorder (MDD) patients before and after 6
      week treatment with antidepressants; these levels were measured in 28 age- and
      sex-matched normal controls. Depression severity was assessed using the Hamilton
      Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated
      using quantitative enzyme-linked immunosorbent assay. RESULTS: Pre-treatment
      plasma levels of IL-23 and IL-17 in MDD patients were not significantly different
      from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6
      weeks of antidepressant treatment were not different from the baseline levels.
      There was no significant correlation between changes in the cytokine levels and
      changes in the HDRS scores representing the severity of depression. CONCLUSION:
      The present study does not support a potential involvement of IL-23 and IL-17
      axis in major depression. Replication and extension using a larger sample are
      required.

PMID- 24302955
TI  - Myasthenia gravis, schizophrenia, and colorectal cancer in a patient: long-term
      follow-up with medication complexity.
AB  - In a case of 46-year-old woman suffering from schizophrenia for over 20 years,
      she experienced frequent episodes of dyspnea and confirmed as superimposed with
      myasthenia gravis (MG). Throughout the seven-year follow-up period, after
      diagnosed as MG, she has been hospitalized 6 times and also diagnosed as
      colorectal cancer. Authors experienced various conditions associated with
      untoward effects of medication for myasthenia, schizophrenia, and colorectal
      cancer. Therefore, authors reported considerations for the pharmacotherapy of
      schizophrenia with myasthenia gravis. 

PMID- 24302956
TI  - Impulsive behavior and recurrent major depression associated with dandy-walker
      variant.
AB  - Reported herein is a case of recurrent major depression with impulse control
      difficulty in a 33-year-old man with Dandy-Walker variant. He was diagnosed as
      having major depressive disorder a year before he presented himself to the
      authors' hospital, and had a history of three-time admission to a psychiatric
      unit in the previous 12 months. He was readmitted and treated with sodium
      valporate 1,500 mg/day, mirtazapine 45 mg/day, and quetiapine 800 mg/day during
      the three months that he was confined in the authors' hospital, and the symptoms
      were reduced within three months but remained thereafter. This is the only case
      so far reporting recurrent depression with impulse control difficulty associated
      with Dandy-Walker variant. This case implies that any cerebellar lesion may cause
      the appearance of recurrent depression with impulse control difficulty in major
      depressive disorder. 

PMID- 24302958
TI  - Molecular profiling of acute and chronic rejections of renal allografts.
AB  - Both antibody mediated (AMR) and T-cell mediated (TCMR) rejections either acute
      or chronic represent the main reason for late graft dysfunction. In this study we
      aimed to evaluate differences in the intrarenal expression patterns of immune
      system related genes in acute and chronic rejections. Graft biopsies were
      performed and evaluated according to Banff classification. Using the TaqMan Low
      Density Array, the intrarenal expressions of 376 genes relating to immune
      response (B-cell activation, T-cell activation, chemokines, growth factors,
      immune regulators, and apoptosis) were analyzed in the four rejection categories:
      chronic AMR, chronic TCMR, acute AMR, and acute TCMR. The set of genes
      significantly upregulated in acute TCMR as compared to acute AMR was identified,
      while no difference in gene expressions between chronic rejections groups was
      found. In comparison with functioning grafts, grafts that failed within the next
      24 months after the chronic rejection morphological confirmation presented at
      biopsy already established severe graft injury (low eGFR, higher proteinuria),
      longer followup, higher expression of CDC20, CXCL6, DIABLO, GABRP, KIAA0101, ME2,
      MMP7, NFATC4, and TGFB3 mRNA, and lower expression of CCL19 and TRADD mRNA. In
      conclusion, both Banff 2007 chronic rejection categories did not differ in
      intrarenal expression of 376 selected genes associated with immune response. 

PMID- 24302957
TI  - Treatment with CB2 agonist JWH-133 reduces histological features associated with
      erectile dysfunction in hypercholesterolemic mice.
AB  - Hypercholesterolemia is one of the most important risk factors for erectile
      dysfunction, mostly due to the impairment of oxidative stress and endothelial
      function in the penis. The cannabinoid system might regulate peripheral
      mechanisms of sexual function; however, its role is still poorly understood. We
      investigated the effects of CB2 activation on oxidative stress and fibrosis
      within the corpus cavernosum of hypercholesterolemic mice. Apolipoprotein-E
      knockout mice were fed with a western-type diet for 11 weeks and treated with JWH
      133 (selective CB2 agonist) or vehicle during the last 3 weeks. CB2 receptor
      expression, total collagen content, and reactive oxygen species (ROS) production
      within the penis were assessed. In vitro corpus cavernosum strips preparation was
      performed to evaluate the nitric oxide (NO) bioavailability. CB2 protein
      expression was shown in cavernosal endothelial and smooth muscle cells of wild
      type and hypercholesterolemic mice. Treatment with JWH-133 reduced ROS production
      and NADPH-oxidase expression in hypercholesterolemic mice penis. Furthermore, JWH
      133 increased endothelial NO synthase expression in the corpus cavernosum and
      augmented NO bioavailability. The decrease in oxidative stress levels was
      accompanied with a reduction in corpus cavernosum collagen content. In summary,
      CB2 activation decreased histological features, which were associated with
      erectile dysfunction in hypercholesterolemic mice. 

PMID- 24302959
TI  - Lipoic acid treatment after brain injury: study of the glial reaction.
AB  - After trauma brain injury, oxidative substances released to the medium provoke an
      enlargement of the initial lesion, increasing glial cell activation and,
      occasionally, an influx of immune cells into the central nervous system,
      developing the secondary damage. In response to these stimuli, microglia are
      activated to perform upregulation of intracellular enzymes and cell surface
      markers to propagate the immune response and phagocytosis of cellular debris. The
      phagocytosis of debris and dead cells is essential to limit the inflammatory
      reaction and potentially prevent extension of the damage to noninjured regions.
      Lipoic acid has been reported as a neuroprotectant by acting as an antioxidant
      and anti-inflammatory agent. Furthermore, angiogenic effect promoted by lipoic
      acid has been recently shown by our group as a crucial process for neural
      regeneration after brain injury. In this work, we focus our attention on the
      lipoic acid effect on astroglial and microglial response after brain injury. 

PMID- 24302960
TI  - Improvement of the dynamic responses of heart rate variability patterns after
      needle and laser acupuncture treatment in patients with burnout syndrome: a
      transcontinental comparative study.
AB  - We investigated manual needle and laser needle acupuncture as a complementary
      therapy for patients with burnout syndrome. Twenty patients with a mean age +/-
      SD of 38.7 +/- 8.4 years were assigned to two groups, each consisting of ten
      patients. One group was treated with manual needle acupuncture and the other with
      laser needle acupuncture. Heart rate, heart rate variability (HRV), and a new
      score called dynamic acupuncture treatment score (DATS) served as evaluation
      parameters. The study documented significant effects on heart rate after needle
      acupuncture treatment and significant effects on HRV caused by both needle and
      laser needle acupuncture. Based on new neurovegetative acupuncture treatment
      evaluation scores, it can be stated that both noninvasive laser needle
      acupuncture and manual needle acupuncture have the potential to be a powerful
      approach for evidence-based complementary treatment of patients with burnout
      syndrome. Further transcontinental studies to verify or refute the preliminary
      findings are in progress. 

PMID- 24302961
TI  - Astragalus Polysaccharide Suppresses the Expression of Adhesion Molecules through
      the Regulation of the p38 MAPK Signaling Pathway in Human Cardiac Microvascular
      Endothelial Cells after Ischemia-Reperfusion Injury.
AB  - Astragalus polysaccharide is a major component of radix astragali, a vital qi
      reinforcing herb medicine with favorable immune-regulating effects. In a previous
      animal experiment, we demonstrated that astragalus polysaccharide effectively
      alleviates ischemia-reperfusion injury (IRI) of cardiac muscle through the
      regulation of the inflammatory reactions. However, the relationship between this
      herb and the cohesion molecules on the cell surface remains controversial. In
      this study, human cardiac microvascular endothelial cells (HCMECs) were used to
      validate the protective effects of astragalus under an IRI scheme simulated
      through hypoxia/reoxygenation in vitro. The results indicated that astragalus
      polysaccharide inhibited the cohesion between HCMECs and polymorphonuclear
      leukocyte (PMN) during IRI through the downregulation of p38 MAPK signaling and
      the reduction of cohesive molecule expression in HCMECs. 

PMID- 24302962
TI  - Ellagic Acid Reduces Adipogenesis through Inhibition of Differentiation
      Prevention of the Induction of Rb Phosphorylation in 3T3-L1 Adipocytes.
AB  - Ellagic acid (EA) present in many fruits and nuts serves as antiproliferation,
      anti-inflammatory, and antitumorigenic properties. However, the effect of EA on
      preadipocytes adipogenesis and its mechanism(s) have not been elucidated. The
      present study was designed to examine the effect of EA on adipogenesis in 3T3-L1
      preadipocytes and underlying mechanism(s) of action involved. Data show that EA
      administration decreased the accumulation of lipid droplets. The inhibition was
      diminished when the addition of EA was delayed to days 2-4 of differentiation.
      Clonal expansion was reduced in the presence of EA. FACS analysis showed that EA
      blocked the cell cycle at the G1/S transition. EdU incorporation also confirmed
      that EA refrained cell from entering S phase. Our data also revealed that the
      differentiation-induced protein expression of Cyclin A and phosphorylation of the
      retinoblastoma protein (Rb) were impaired by EA. Differentiation-dependent
      expression and DNA-binding ability of C/EBP alpha were also inhibited by EA.
      Alterations in cell cycle-associated proteins may be important with respect to
      the antiadipogenic action of EA. In conclusion, EA is capable of inhibiting
      adipogenesis in 3T3-L1 adipocytes possibly through reduction of Cyclin A protein
      expression and Rb phosphorylation. With the blocking of G1/S phase transition, EA
      suppresses terminal differentiation and lipid accumulation in 3T3-L1 adipocytes. 

PMID- 24302963
TI  - Screening and Scoring of Antimicrobial and Biological Activities of Italian
      Vulnerary Plants against Major Oral Pathogenic Bacteria.
AB  - This study aims to evaluate the activity of Italian vulnerary plants against the
      most important oral pathogenic bacteria. This estimate was accomplished through a
      fivefold process: (a) a review of ethnobotanical and microbiological data
      concerning the Italian vulnerary plants; (b) the development of a scoring system
      to rank the plants; (c) the comparative assessment of microbiological properties;
      (d) the assessment of potential cytotoxic effects on keratinocyte-like cells and
      gingival fibroblasts in culture by XTT cell viability assay; (e) clinical
      evaluation of the most suitable plant extract as antibacterial agent in a home
      made mouthwash. The study assays hexane (H), ethanol (E), and water (W) extracts
      from 72 plants. The agar diffusion method was used to evaluate the activity
      against Streptococcus mutans, Streptococcus sobrinus, Lactobacillus casei, and
      Actinomyces viscosus. Twenty-two plants showed appreciable activity. The extracts
      showing the strongest antibacterial power were those from Cotinus coggygria
      Scop., Equisetum hyemale L., Helichrysum litoreum Guss, Juniperus communis L.,
      and Phyllitis scolopendrium (L.) Newman subsp. scolopendrium. The potential
      cytotoxic effect of these extracts was assessed. On the basis of these
      observations, a mouth-rinse containing the ethanolic extract of H. litoreum has
      been tested in vivo, resulting in reduction of the salivary concentration of S.
      mutans. 

PMID- 24302964
TI  - Recent highlights of metabolomics in chinese medicine syndrome research.
AB  - Chinese medicine syndrome (CMS, "ZHENG" in Chinese) is an understanding of the
      regularity of disease occurrence and development as well as a certain stage of a
      comprehensive response of patients with body condition. However, because of the
      complexity of CMS and the limitation of present investigation method, the
      research for deciphering the scientific basis and systematic features of CMS is
      difficult to go further. Metabolomics enables mapping of early biochemical
      changes in disease and hence provides an opportunity to develop predictive
      biomarkers. Moreover, its method and design resemble those of traditional Chinese
      medicine (TCM) which focuses on human disease via the integrity of close
      relationship between body and syndromes. In the systemic context, metabolomics
      has a convergence with TCM syndrome; therefore it could provide useful tools for
      exploring essence of CMS disease, facilitating personalized TCM, and will help to
      in-depth understand CMS. The integration of the metabolomics and CMS aspects will
      give promise to bridge the gap between Chinese and Western medicine and help
      catch the traditional features of CMS. In this paper, particular attention will
      be paid to the past successes in applications of robust metabolomic approaches to
      contribute to low-molecular-weight metabolites (biomarkers) discovery in CMS
      research and development. 

PMID- 24302965
TI  - Pectinesterase Inhibitor from Jelly Fig (Ficus awkeotsang Makino) Achene Inhibits
      Surface Antigen Expression by Human Hepatitis B Virus.
AB  - Pectinesterase inhibitor (PEI) isolated from jelly fig (Ficus awkeotsang Makino)
      is an edible component of a popular drink consumed in Asia. Hepatitis B virus
      (HBV) infection is prevalent in Asia, and current treatments for HBV infection
      need improvement. This study aimed to evaluate the effect of PEI on the surface
      antigen expression by HBV (HBsAg). Human hepatoma cell lines Hep3B and Huh7
      served as in vitro models for assessing the cytotoxicity and HBsAg expression. A
      culture of primary hepatocytes cultured from mice served as the normal
      counterpart. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) colorimetric assay. HBsAg expression was
      evaluated by measuring HBsAg secretion into the culture medium using an enzyme
      linked immunosorbent assay. The results showed that PEI did not affect the
      viability of the human hepatoma cell lines or primary mouse hepatocytes. PEI
      inhibited the expression of HBsAg in hepatoma cell lines harboring endogenous
      (Hep3B) and integrated (Huh7) HBV genomes in a concentration- and time-dependent
      manner, thus implicating a universal activity against HBV gene expression. In
      conclusion, it suggests that PEI from jelly fig inhibits the expression of human
      HBsAg in host cells without toxic effects on normal primary hepatocytes. 

PMID- 24302966
TI  - Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.)
      Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats.
AB  - Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective
      effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in
      Sprague Dawley rats were investigated. The possible involvements of lipid
      peroxidation, superoxide dismutase, and catalase were also investigated. Acute
      toxicity study was performed. The effects of aqueous extract of H. erinaceus on
      the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological
      gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were
      evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose
      of 5 g/kg did not manifest any toxicological signs in rats. The extract promoted
      ulcer protection as ascertained by a significant reduction of the ulcer area.
      Furthermore, it exhibited a significant protection activity against gastric
      mucosal injury by preventing the depletion of antioxidant enzymes. The level of
      MDA was also limited in rat stomach tissues when compared with the ulcer control
      group. Immunohistochemistry showed upregulation of HSP70 protein and
      downregulation of BAX protein in rats pretreated with the extract. The aqueous
      extract of H. erinaceus protected gastric mucosa in our in vivo model. It is
      speculated that the bioactive compounds present in the extract may play a major
      role in gastroprotective activity. 

PMID- 24302967
TI  - The research of acupuncture effective biomolecules: retrospect and prospect.
AB  - Acupuncture is an effective, safe and convenient therapy that has been applied
      for 2,500 years. The acupuncture researches have obtained significant improvement
      with the technical support of the life sciences and the studies of acupuncture
      have in turn accelerated the development of biomedical science. The effects of
      acupuncture influence important physiopathologic and biological activities,
      including gene expression, protein-protein interactions, and other biological
      processes. Cerebrospinal fluid, serum, organs, and tissues are reported to be
      carriers of the biomolecules of the effects of acupuncture. The paper summarized
      the progress of acupuncture effective biomolecules researches and found that
      biomolecules play important roles in the mechanism of acupuncture. With the
      development of omics technologies and translational medicine, the acupuncture
      research will meet both opportunities and challenges. 

PMID- 24302968
TI  - The historical development of deqi concept from classics of traditional chinese
      medicine to modern research: exploitation of the connotation of deqi in chinese
      medicine.
AB  - Although it is difficult in fully clarifying its mechanisms and effects, Deqi
      still can be considered as an instant "sign" of acupuncture response of the
      patient and acupuncturist, which has a significant value in clinic and research.
      This paper aims to take a history trace to the development of Deqi theory,
      understand the connotation of Deqi based on Chinese medicine theory, and
      establish an evaluation methodology accordingly. We believe that Deqi is not only
      the needling sensation, but also the perception of changes of qi (') flowing of
      the patient elicited by needling on acupoints. The signs of Deqi include the
      patient's subjective perception (needling sensation), the objective physiological
      changes (common referred to the skin redness around the acupoints and the
      response of brain), and the acupuncturists' perception. Although Deqi is
      essential for attaining the effect, it may not be the necessary sign of the ideal
      efficacy. It is found that the characteristics of Deqi sensations, Deqi's
      intensity, time duration, and the propagation will all affect the efficacy. Thus,
      acupuncturists should pay attention to elicit and control Deqi state, which is
      also the key point in modern research on the therapeutic implications of Deqi. 

PMID- 24302969
TI  - Chemical Composition and Validation of the Ethnopharmacological Reported
      Antimicrobial Activity of the Body Fat of Phrynops geoffroanus Used in
      Traditional Medicine.
AB  - Background. Phrynops geoffroanus is a small turtle that inhabits lakes, rivers,
      and streams throughout South America. The body fat of this animal is used as a
      folk medicine in Brazil for treating illnesses such as sore throats, ear aches,
      mumps, rheumatism, and arthritis. The present study evaluated the antimicrobial
      activity of oil extracted from Phrynops geoffroanus (OPG), determined its
      chemical composition, and discussed the implications of its use in traditional
      medicine. The OPG was obtained from the ventral region of this turtle using
      hexane as a solvent. The antimicrobial activity of OPG was tested against
      standard and multiresistance strains of bacteria and fungi and its composition
      was determined indirectly by analyzing the methyl esters of the component fatty
      acids. The OPG presented a clinically relevant antifungal activity against
      Candida krusei ATCC 6258 (MIC 128 ug/mL). When the OPG was associated with the
      antibacterial and antifungal drugs, was observed a synergistic effect when
      associated the OPG with the gentamicin against the strain Pseudomonas aeruginosa
      22. Our results indicated that OPG has clinically relevant antifungal activity
      against C. krusei, and demonstrated synergetic antibacterial activity in
      combination with commercial antibiotics against Pseudomonas aeruginosa. 

PMID- 24302970
TI  - Immunomodulatory Role of an Ayurvedic Formulation on Imbalanced Immunometabolics
      during Inflammatory Responses of Obesity and Prediabetic Disease.
AB  - Kal-1 is a polyherbal decoction of seven different natural ingredients,
      traditionally used in controlling sugar levels, inflammatory conditions
      particularly regulating metabolic and immunoinflammatory balance which are the
      major factors involved in obesity and related diseases. In the present study, we
      aimed to investigate the effect of Kal-1 (an abbreviation derived from the
      procuring source) on diet-induced obesity and type II diabetes using C57BL/6J
      mice as a model. The present study was performed with two experimental groups
      involving obese and prediabetic mice as study animals. In one, the mice were fed
      on high-fat with increased sucrose diet, and different amounts (5, 20, and 75  MU
      L) of Kal-1 were administered with monitoring of disease progression over a
      period of 21 weeks whereas in the second group the mice were first put on the
      same diet for 21 weeks and then treated with the same amounts of Kal-1. A
      significant reduction in body weight, fat pads, fasting blood glucose levels,
      insulin levels, biochemical parameters, immunological parameters, and an array of
      pro- and anticytokines was observed in obese and diabetic mice plus Kal-1 than
      control (lean) mice fed on normal diet. In conclusion, Kal-1 has immunomodulatory
      potential for diet-induced obesity and associated metabolic disorders. 

PMID- 24302971
TI  - Acetylshikonin, a Novel AChE Inhibitor, Inhibits Apoptosis via Upregulation of
      Heme Oxygenase-1 Expression in SH-SY5Y Cells.
AB  - Acetylcholinesterase inhibitors are prominent alternative in current clinical
      treatment for AD patients. Therefore, there is a continued need to search for
      novel AChEIs with good clinical efficacy and less side effects. By using our in
      house natural product database and AutoDock Vina as a tool in docking study, we
      have identified twelve phytochemicals (emodin, aloe-emodin, chrysophanol, and
      rhein in Rhei Radix Et Rhizoma; xanthotoxin, phellopterin, alloisoimperatorin,
      and imperatorin in Angelicae dahuricae Radix; shikonin, acetylshikonin,
      isovalerylshikonin, and beta,beta-dimethylacrylshikonin in Arnebiae Radix) as
      candidates of AChEIs that were not previously reported in the literature. In
      addition to AChEI activity, a series of cell-based experiments were conducted for
      the investigation of their neuroprotective activities. We found that
      acetylshikonin and its derivatives prevented apoptotic cell death induced by
      hydrogen peroxide in human and rat neuronal SH-SY5Y and PC12 cells at 10 MUM. We
      showed that acetylshikonin exhibited the most potent antiapoptosis activity
      through the inhibition of the generation of reactive oxygen species as well as
      protection of the loss of mitochondria membrane potential. Furthermore, we
      identified for the first time that the upregulation of heme oxygenase 1 by
      acetylshikonin is a key step mediating its antiapoptotic activity from oxidative
      stress in SH-SY5Y cells. 

PMID- 24302972
TI  - 3D analysis of the proximal interphalangeal joint kinematics during flexion.
AB  - BACKGROUND: Dynamic joint motion recording combined with CT-based 3D bone and
      joint surface data is accepted as a helpful and precise tool to analyse joint.
      The purpose of this study is to demonstrate the feasibility of these techniques
      for quantitative motion analysis of the interphalangeal joint in 3D. MATERIALS
      AND METHOD: High resolution motion data was combined with an accurate 3D model of
      a cadaveric index finger. Three light-emitting diodes (LEDs) were used to record
      dynamic data, and a CT scan of the finger was done for 3D joint surface geometry.
      The data allowed performing quantitative evaluations such as finite helical axis
      (FHA) analysis, coordinate system optimization, and measurement of the joint
      distances in 3D. RESULTS: The FHA varies by 4.9 +/- 1.7 degrees  on average. On
      average, the rotation in adduction/abduction and internal/external rotation were
      0.3 +/- 0.91 degrees  and 0.1 +/- 0.97 degrees , respectively. During flexion, a
      translational motion between 0.06 mm and 0.73 mm was observed. CONCLUSIONS: The
      proposed technique and methods appear to be feasible for the accurate assessment
      and evaluation of the PIP joint motion in 3D. The presented method may help to
      gain additional insights for the design of prosthetic implants, rehabilitation,
      and new orthotic devices.

PMID- 24302973
TI  - Application of computational lower extremity model to investigate different
      muscle activities and joint force patterns in knee osteoarthritis patients during
      walking.
AB  - Many experimental and computational studies have reported that osteoarthritis in
      the knee joint affects knee biomechanics, including joint kinematics, joint
      contact forces, and muscle activities, due to functional restriction and
      disability. In this study, differences in muscle activities and joint force
      patterns between knee osteoarthritis (OA) patients and normal subjects during
      walking were investigated using the inverse dynamic analysis with a lower
      extremity musculoskeletal model. Extensor/flexor muscle activations and torque
      ratios and the joint contact forces were compared between the OA and normal
      groups. The OA patients had higher extensor muscle forces and lateral component
      of the knee joint force than normal subjects as well as force and torque ratios
      of extensor and flexor muscles, while the other parameters had little
      differences. The results explained that OA patients increased the level of
      antagonistic cocontraction and the adduction moment on the knee joint. The
      presented findings and technologies provide insight into biomechanical changes in
      OA patients and can also be used to evaluate the postoperative functional
      outcomes of the OA treatments. 

PMID- 24302974
TI  - Level set segmentation of medical images based on local region statistics and
      maximum a posteriori probability.
AB  - This paper presents a variational level set method for simultaneous segmentation
      and bias field estimation of medical images with intensity inhomogeneity. In our
      model, the statistics of image intensities belonging to each different tissue in
      local regions are characterized by Gaussian distributions with different means
      and variances. According to maximum a posteriori probability (MAP) and Bayes'
      rule, we first derive a local objective function for image intensities in a
      neighborhood around each pixel. Then this local objective function is integrated
      with respect to the neighborhood center over the entire image domain to give a
      global criterion. In level set framework, this global criterion defines an energy
      in terms of the level set functions that represent a partition of the image
      domain and a bias field that accounts for the intensity inhomogeneity of the
      image. Therefore, image segmentation and bias field estimation are simultaneously
      achieved via a level set evolution process. Experimental results for synthetic
      and real images show desirable performances of our method. 

PMID- 24302975
TI  - Location of the mandibular canal and thickness of the occlusal cortical bone at
      dental implant sites in the lower second premolar and first molar.
AB  - The objective of this study was to evaluate the location of the mandibular canal
      and the thickness of the occlusal cortical bone at dental implant sites in the
      lower second premolar and lower first molar by using dental cone-beam computed
      tomography (CBCT). Seventy-nine sites (47 second premolar and 32 first molar
      sites) were identified in the dental CBCT examinations of 47 patients. In this
      study, 4 parameters were measured: (1) MC-the distance from the mandibular canal
      to the upper border of the mandible; (2) CD-the distance from the mandibular
      canal to the buccal border of the mandible; (3) MD-the distance from the
      mandibular canal to the lingual border of the mandible; (4) TC-the thickness of
      the cortical bone at the occlusal side. A statistical analysis was employed to
      compare the size and differences between these 4 parameters at the lower second
      premolar and lower first molar. Regarding the MC and MD, the experimental results
      showed no statistical difference between the first molar and second premolar.
      However, the TC for the second premolar was greater than that of the first molar.
      Thus, careful consideration is necessary in choosing the size of and operation
      type for dental implants. 

PMID- 24302976
TI  - Antibacterial activity of biosecur((r)) citrus extract surface cleaner against
      Vibrio vulnificus.
AB  - This study evaluated the antibacterial activity of Biosecur((r)) citrus extract
      surface cleaner against Vibrio vulnificus using plate count method. Two
      concentrations, 0.5% and 2% of Biosecur((r)) surface cleaner were plated on
      Vibrio vulnificus Agar (VVA) and tested for reduction of Vibrio vulnificus. In
      order to investigate the lasting residual activity of Biosecur((r)),
      antibacterial activity tests were also performed at time intervals up to 2.5 h
      after Biosecur((r)) was plated on VVA. Biosecur((r)) showed 6-log reduction of
      Vibrio vulnificus at 2%, and 3-log reduction of Vibrio vulnificus at 0.5%. The
      antibacterial activity of 2% Biosecur((r)) against Vibrio vulnificus was shown to
      be equivalent to that of tetracycline. The residual activity of 2% Biosecur((r))
      was shown to maintain for at least 2.5 h after application. This study confirmed
      the high activity and long lasting residual effect of a safe, non-toxic organic
      food grade surface cleaner. 

PMID- 24302977
TI  - A P300-based brain-computer interface with stimuli on moving objects: four
      session single-trial and triple-trial tests with a game-like task design.
AB  - Brain-computer interfaces (BCIs) are tools for controlling computers and other
      devices without using muscular activity, employing user-controlled variations in
      signals recorded from the user's brain. One of the most efficient noninvasive
      BCIs is based on the P300 wave of the brain's response to stimuli and is
      therefore referred to as the P300 BCI. Many modifications of this BCI have been
      proposed to further improve the BCI's characteristics or to better adapt the BCI
      to various applications. However, in the original P300 BCI and in all of its
      modifications, the spatial positions of stimuli were fixed relative to each
      other, which can impose constraints on designing applications controlled by this
      BCI. We designed and tested a P300 BCI with stimuli presented on objects that
      were freely moving on a screen at a speed of 5.4 degrees /s. Healthy participants
      practiced a game-like task with this BCI in either single-trial or triple-trial
      mode within four sessions. At each step, the participants were required to select
      one of nine moving objects. The mean online accuracy of BCI-based selection was
      81% in the triple-trial mode and 65% in the single-trial mode. A relatively high
      P300 amplitude was observed in response to targets in most participants. Self
      rated interest in the task was high and stable over the four sessions (the
      medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing
      in the single-trial and triple-trial modes, respectively). We conclude that the
      movement of stimulus positions relative to each other may not prevent the
      efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic
      devices and in video games. 

PMID- 24302978
TI  - Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by
      insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of
      GLP-1 isoforms.
AB  - BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy.
      However, their underlying mechanisms have not been elucidated, leading to a lack
      of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces
      hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto
      Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti
      hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure
      and function assessment, plasma and left ventricles were isolated for biochemical
      studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.
      RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1
      decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged
      deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and
      fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin
      lessened all these parameters. In cultured cardiomyocytes and cardiac
      fibroblasts, high-concentration of palmitate or glucose induced cell-death,
      hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive
      metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a
      specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms
      attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In
      addition, GLP-1 receptor signalling may be linked to PPARdelta activation, and
      metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct
      effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization,
      promoted cardioprotection in type-II diabetic hearts primarily by limiting
      hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival
      and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell
      autonomous cardioprotective actions.

PMID- 24302979
TI  - Sialoglycoproteins and N-glycans from secreted exosomes of ovarian carcinoma
      cells.
AB  - Exosomes consist of vesicles that are secreted by several human cells, including
      tumor cells and neurons, and they are found in several biological fluids.
      Exosomes have characteristic protein and lipid composition, however, the results
      concerning glycoprotein composition and glycosylation are scarce. Here, protein
      glycosylation of exosomes from ovarian carcinoma SKOV3 cells has been studied by
      lectin blotting, NP-HPLC analysis of 2-aminobenzamide labeled glycans and mass
      spectrometry. An abundant sialoglycoprotein was found enriched in exosomes and it
      was identified by peptide mass fingerprinting and immunoblot as the galectin-3
      binding protein (LGALS3BP). Exosomes were found to contain predominantly complex
      glycans of the di-, tri-, and tetraantennary type with or without proximal fucose
      and also high mannose glycans. Diantennary glycans containing bisecting N
      acetylglucosamine were also detected. This work provides detailed information
      about glycoprotein and N-glycan composition of exosomes from ovarian cancer
      cells, furthermore it opens novel perspectives to further explore the functional
      role of glycans in the biology of exosomes. 

PMID- 24302980
TI  - More than meets the eye: associations of vaginal bacteria with gram stain
      morphotypes using molecular phylogenetic analysis.
AB  - Bacterial vaginosis (BV) is a highly prevalent condition associated with adverse
      health outcomes. Gram stain analysis of vaginal fluid is the standard for
      confirming the diagnosis of BV, wherein abundances of key bacterial morphotypes
      are assessed. These Lactobacillus, Gardnerella, Bacteroides, and Mobiluncus
      morphotypes were originally linked to particular bacterial species through
      cultivation studies, but no studies have systematically investigated associations
      between uncultivated bacteria detected by molecular methods and Gram stain
      findings. In this study, 16S-rRNA PCR/pyrosequencing was used to examine
      associations between vaginal bacteria and bacterial morphotypes in 220 women with
      and without BV. Species-specific quantitative PCR (qPCR) and fluorescence in Situ
      hybridization (FISH) methods were used to document concentrations of two bacteria
      with curved rod morphologies: Mobiluncus and the fastidious BV-associated
      bacterium-1 (BVAB1). Rank abundance of vaginal bacteria in samples with evidence
      of curved gram-negative rods showed that BVAB1 was dominant (26.1%), while
      Mobiluncus was rare (0.2% of sequence reads). BVAB1 sequence reads were
      associated with Mobiluncus morphotypes (p<0.001). Among women with curved rods,
      mean concentration of BVAB1 DNA was 2 log units greater than Mobiluncus (p<0.001)
      using species-specific quantitative PCR. FISH analyses revealed that mean number
      of BVAB1 cells was 2 log units greater than Mobiluncus cells in women with
      highest Nugent score (p<0.001). Prevotella and Porphyromonas spp. were
      significantly associated with the "Bacteroides morphotype," whereas Bacteroides
      species were rare. Gram-negative rods designated Mobiluncus morphotypes on Gram
      stain are more likely BVAB1. These findings provide a clearer picture of the
      bacteria associated with morphotypes on vaginal Gram stain. 

PMID- 24302981
TI  - Peripapillary intrachoroidal cavitations. The Beijing eye study.
AB  - PURPOSE: To assess prevalence, size and location of peripapillary intrachoroidal
      cavitations (PICCs) and their associations in a population-based sample. .
      METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals
      with a mean age of 64.6 +/- 9.8 years (range:50-93 years). A detailed ophthalmic
      examination included enhanced depth imaging of the choroid by spectral-domain
      optical coherence tomography and fundus photography. PICCs were defined as
      triangular thickening of the choroid with the base at the optic disc border and a
      distance between Bruch's membrane and sclera of >= 200 MUm. Parapapillary large
      choroidal vessels were excluded. RESULTS: Out of 94 subjects with high myopia
      (refractive error <-6.0 diopters or axial length >26.5mm in right eyes), OCT
      images were available for 89 (94.7%) participants. A PICC was detected in 15 out
      of these 89 highly myopic subjects (prevalence:16.9 +/- 4.0%) and in none of
      hyperopic, emmetropic or medium myopic subgroups each consisting of 100 randomly
      selected subjects. Mean PICC width was 4.2 +/- 2.3 hours (30 degrees ) of disc
      circumference and mean length was 1363 +/- 384 MUm. PICCs were located most
      frequently (40%) at the inferior disc border. On fundus photos, a typical yellow
      orange lesion was found in 8 (53%) eyes with PICCs. In binary regression
      analysis, presence of PICCs was significantly associated with optic disc tilting
      (P=0.04) and presence of posterior staphylomata (P=0.046). CONCLUSIONS:
      Prevalence of PICCs in the adult Chinese population was 16.9 +/- 4.0% in the
      highly myopic group, with no PICCs detected in non-highly myopic eyes. PICCs were
      located most frequently at the inferior optic disc border. Only half of the PICCs
      detected on OCT images showed a yellow-orange lesion on fundus photos. Presence
      of PICC was significantly associated only with an increased optic disc tilting
      and presence of posterior staphylomata, while it was not associated with axial
      length, refractive error or other ocular or systemic parameters.

PMID- 24302983
TI  - A stochastic multi-scale model of HIV-1 transmission for decision-making:
      application to a MSM population.
AB  - BACKGROUND: In the absence of an effective vaccine against HIV-1, the scientific
      community is presented with the challenge of developing alternative methods to
      curb its spread. Due to the complexity of the disease, however, our ability to
      predict the impact of various prevention and treatment strategies is limited.
      While ART has been widely accepted as the gold standard of modern care, its
      timing is debated. OBJECTIVES: To evaluate the impact of medical interventions at
      the level of individuals on the spread of infection across the whole population.
      Specifically, we investigate the impact of ART initiation timing on HIV-1 spread
      in an MSM (Men who have Sex with Men) population. DESIGN AND METHODS: A
      stochastic multi-scale model of HIV-1 transmission that integrates within a
      single framework the in-host cellular dynamics and their outcomes, patient health
      states, and sexual contact networks. The model captures disease state and
      progression within individuals, and allows for simulation of therapeutic
      strategies. RESULTS: Early ART initiation may substantially affect disease spread
      through a population. CONCLUSIONS: Our model provides a multi-scale, systems
      based approach to evaluate the broader implications of therapeutic strategies.

PMID- 24302984
TI  - Do basal Ganglia amplify willed action by stochastic resonance? A model.
AB  - Basal ganglia are usually attributed a role in facilitating willed action, which
      is found to be impaired in Parkinson's disease, a pathology of basal ganglia. We
      hypothesize that basal ganglia possess the machinery to amplify will signals,
      presumably weak, by stochastic resonance. Recently we proposed a computational
      model of Parkinsonian reaching, in which the contributions from basal ganglia aid
      the motor cortex in learning to reach. The model was cast in reinforcement
      learning framework. We now show that the above basal ganglia computational model
      has all the ingredients of stochastic resonance process. In the proposed
      computational model, we consider the problem of moving an arm from a rest
      position to a target position: the two positions correspond to two extrema of the
      value function. A single kick (a half-wave of sinusoid, of sufficiently low
      amplitude) given to the system in resting position, succeeds in taking the system
      to the target position, with high probability, only at a critical noise level.
      But for suboptimal noise levels, the model arm's movements resemble Parkinsonian
      movement symptoms like akinetic rigidity (low noise) and dyskinesias (high
      noise). 

PMID- 24302985
TI  - Direct evidence that scorpion alpha-toxins (site-3) modulate sodium channel
      inactivation by hindrance of voltage-sensor movements.
AB  - The position of the voltage-sensing transmembrane segment, S4, in voltage-gated
      ion channels as a function of voltage remains incompletely elucidated. Site-3
      toxins bind primarily to the extracellular loops connecting transmembrane helical
      segments S1-S2 and S3-S4 in Domain 4 (D4) and S5-S6 in Domain 1 (D1) and slow
      fast-inactivation of voltage-gated sodium channels. As S4 of the human skeletal
      muscle voltage-gated sodium channel, hNav1.4, moves in response to depolarization
      from the resting to the inactivated state, two D4S4 reporters (R2C and R3C,
      Arg1451Cys and Arg1454Cys, respectively) move from internal to external positions
      as deduced by reactivity to internally or externally applied sulfhydryl group
      reagents, methane thiosulfonates (MTS). The changes in reporter reactivity, when
      cycling rapidly between hyperpolarized and depolarized voltages, enabled
      determination of the positions of the D4 voltage-sensor and of its rate of
      movement. Scorpion alpha-toxin binding impedes D4S4 segment movement during
      inactivation since the modification rates of R3C in hNav1.4 with
      methanethiosulfonate (CH3SO2SCH2CH2R, where R = -N(CH3)3 (+) trimethylammonium,
      MTSET) and benzophenone-4-carboxamidocysteine methanethiosulfonate (BPMTS) were
      slowed ~10-fold in toxin-modified channels. Based upon the different size,
      hydrophobicity and charge of the two reagents it is unlikely that the change in
      reactivity is due to direct or indirect blockage of access of this site to
      reagent in the presence of toxin (Tx), but rather is the result of inability of
      this segment to move outward to the normal extent and at the normal rate in the
      toxin-modified channel. Measurements of availability of R3C to internally applied
      reagent show decreased access (slower rates of thiol reaction) providing further
      evidence for encumbered D4S4 movement in the presence of toxins consistent with
      the assignment of at least part of the toxin binding site to the region of D4S4
      region of the voltage-sensor module. 

PMID- 24302987
TI  - Long-term monitoring of rainfed wheat yield and soil water at the loess plateau
      reveals low water use efficiency.
AB  - Increasing crop yield and water use efficiency (WUE) in dryland farming requires
      a quantitative understanding of relationships between crop yield and the water
      balance over many years. Here, we report on a long-term dryland monitoring site
      at the Loess Plateau, Shanxi, China, where winter wheat was grown for 30
      consecutive years and soil water content (0-200 cm) was measured every 10 days.
      The monitoring data were used to calibrate the AquaCrop model and then to analyse
      the components of the water balance. There was a strong positive relationship
      between total available water and mean cereal yield. However, only one-third of
      the available water was actually used by the winter wheat for crop transpiration.
      The remaining two-thirds were lost by soil evaporation, of which 40 and 60% was
      lost during the growing and fallow seasons, respectively. Wheat yields ranged
      from 0.6 to 3.9 ton/ha and WUE from 0.3 to 0.9 kg/m(3). Results of model
      experiments suggest that minimizing soil evaporation via straw mulch or plastic
      film covers could potentially double wheat yields and WUE. We conclude that the
      relatively low wheat yields and low WUE were mainly related to (i) limited
      rainfall, (ii) low soil water storage during fallow season due to large soil
      evaporation, and (iii) poor synchronisation of the wheat growing season to the
      rain season. The model experiments suggest significant potential for increased
      yields and WUE. 

PMID- 24302986
TI  - Phylogeny of a genomically diverse group of elymus (poaceae) allopolyploids
      reveals multiple levels of reticulation.
AB  - The grass tribe Triticeae (=Hordeeae) comprises only about 300 species, but it is
      well known for the economically important crop plants wheat, barley, and rye. The
      group is also recognized as a fascinating example of evolutionary complexity,
      with a history shaped by numerous events of auto- and allopolyploidy and apparent
      introgression involving diploids and polyploids. The genus Elymus comprises a
      heterogeneous collection of allopolyploid genome combinations, all of which
      include at least one set of homoeologs, designated St, derived from
      Pseudoroegneria. The current analysis includes a geographically and genomically
      diverse collection of 21 tetraploid Elymus species, and a single hexaploid
      species. Diploid and polyploid relationships were estimated using four molecular
      data sets, including one that combines two regions of the chloroplast genome, and
      three from unlinked nuclear genes: phosphoenolpyruvate carboxylase, beta-amylase,
      and granule-bound starch synthase I. Four gene trees were generated using maximum
      likelihood, and the phylogenetic placement of the polyploid sequences reveals
      extensive reticulation beyond allopolyploidy alone. The trees were interpreted
      with reference to numerous phenomena known to complicate allopolyploid
      phylogenies, and introgression was identified as a major factor in their history.
      The work illustrates the interpretation of complicated phylogenetic results
      through the sequential consideration of numerous possible explanations, and the
      results highlight the value of careful inspection of multiple independent
      molecular phylogenetic estimates, with particular focus on the differences among
      them. 

PMID- 24302988
TI  - The role of snx41-based pexophagy in magnaporthe development.
AB  - Pexophagy, the degradation of peroxisomes via selective autophagy, depends on
      Atg20/Snx42 function in Saccharomyces cerevisiae. Besides its role in selective
      autophagy, Atg20/Snx42 is also involved in an autophagy-independent endosomal
      retrieval trafficking, in cooperation with two other sorting nexins, Snx41 and
      Snx4. Recently, we reported that the sorting nexin MoSnx41, which showed high
      sequence similarity to yeast Snx41 and Snx42/Atg20 proteins, regulates the gamma
      glutamyl cycle and GSH production and is essential for conidiation and
      pathogenicity in Magnaporthe oryzae. Pexophagy was also found to be defective in
      Mosnx41Delta mutant. These findings indicate that MoSnx41 likely serves combined
      functions of Snx42/Atg20 and Snx41 in M. oryzae.. In this study, we performed
      complementation analyses and demonstrate that MoSnx41 alone serves the dual
      function of protein sorting (ScSnx41) and pexophagy (ScSnx42/Atg20). To study the
      potential biological function of pexophagy in fungal pathogenic life cycle, we
      created deletion mutants of potential pexophagy-specific genes, and characterized
      them in terms of pexophagy, conidiation and pathogenesis. We identified Pex14 as
      an essential protein for pexophagy in M. oryzae. Overall, our results show that
      pexophagy per se is not essential for asexual development or virulence in M.
      oryzae. 

PMID- 24302989
TI  - Adsorption properties of tetracycline onto graphene oxide: equilibrium, kinetic
      and thermodynamic studies.
AB  - Graphene oxide (GO) nanoparticle is a high potential effective absorbent.
      Tetracycline (TC) is a broad-spectrum antibiotic produced, indicated for use
      against many bacterial infections. In the present research, a systematic study of
      the adsorption and release process of tetracycline on GO was performed by varying
      pH, sorption time and temperature. The results of our studies showed that
      tetracycline strongly loads on the GO surface via pi-pi interaction and cation-pi
      bonding. Investigation of TC adsorption kinetics showed that the equilibrium was
      reached within 15 min following the pseudo-second-order model with observed rate
      constants of k2 = 0.2742-0.5362 g/mg min (at different temperatures). The
      sorption data has interpreted by the Langmuir model with the maximum adsorption
      of 323 mg/g (298 K). The mean energy of adsorption was determined 1.83 kJ/mol
      (298 K) based on the Dubinin-Radushkevich (D-R) adsorption isotherm. Moreover,
      the thermodynamic parameters such as DeltaH degrees , DeltaS degrees  and DeltaG
      degrees  values for the adsorption were estimated which indicated the endothermic
      and spontaneous nature of the sorption process. The electrochemistry approved an
      ideal reaction for the adsorption under electrodic process. Simulation of GO and
      TC was done by LAMMPS. Force studies in z direction showed that tetracycline
      comes close to GO sheet by C8 direction. Then it goes far and turns and again
      comes close from amine group to the GO sheet. 

PMID- 24302990
TI  - Mapping and deciphering neural codes of NMDA receptor-dependent fear memory
      engrams in the hippocampus.
AB  - Mapping and decoding brain activity patterns underlying learning and memory
      represents both great interest and immense challenge. At present, very little is
      known regarding many of the very basic questions regarding the neural codes of
      memory: are fear memories retrieved during the freezing state or non-freezing
      state of the animals? How do individual memory traces give arise to a holistic,
      real-time associative memory engram? How are memory codes regulated by synaptic
      plasticity? Here, by applying high-density electrode arrays and dimensionality
      reduction decoding algorithms, we investigate hippocampal CA1 activity patterns
      of trace fear conditioning memory code in inducible NMDA receptor knockout mice
      and their control littermates. Our analyses showed that the conditioned tone (CS)
      and unconditioned foot-shock (US) can evoke hippocampal ensemble responses in
      control and mutant mice. Yet, temporal formats and contents of CA1 fear memory
      engrams differ significantly between the genotypes. The mutant mice with disabled
      NMDA receptor plasticity failed to generate CS-to-US or US-to-CS associative
      memory traces. Moreover, the mutant CA1 region lacked memory traces for "what at
      when" information that predicts the timing relationship between the conditioned
      tone and the foot shock. The degraded associative fear memory engram is further
      manifested in its lack of intertwined and alternating temporal association
      between CS and US memory traces that are characteristic to the holistic memory
      recall in the wild-type animals. Therefore, our study has decoded real-time
      memory contents, timing relationship between CS and US, and temporal organizing
      patterns of fear memory engrams and demonstrated how hippocampal memory codes are
      regulated by NMDA receptor synaptic plasticity. 

PMID- 24302991
TI  - miR-146a enhances the oncogenicity of oral carcinoma by concomitant targeting of
      the IRAK1, TRAF6 and NUMB genes.
AB  - MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial
      to tumorigenesis. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy
      worldwide. Up-regulation of miR-146 has been identified in OSCC tissues. However,
      the roles of miR-146 in carcinogenesis are controversial as it is suppressive in
      many other malignancies. The present study investigated the pathogenic
      implications of miR-146a in oral carcinogenesis. Microdissected OSCC exhibits
      higher levels of miR-146a expression than matched adjacent mucosal cells. The
      plasma miR-146a levels of patients are significantly higher than those of control
      subjects; these levels decrease drastically after tumor resection. miR-146a
      levels in tumors and in patients' plasma can be used to classify OSCC and non
      disease status (sensitivity: >0.72). Exogenous miR-146a expression is
      significantly increased in vitro oncogenic phenotypes as well as during xenograft
      tumorigenesis and OSCC metastasis. The plasma miR-146a levels of these mice
      parallel the xenograft tumor burdens of the mice. A miR-146a blocker abrogates
      the growth of xenograft tumors. miR-146a oncogenic activity is associated with
      down-regulation of IRAK1, TRAF6 and NUMB expression. Furthermore, miR-146a
      directly targets the 3'UTR of NUMB and a region within the NUMB coding sequence
      when suppressing NUMB expression. Exogenous NUMB expression attenuates OSCC
      oncogenicity. Double knockdown of IRAK1 and TRAF6, and of TRAF6 and NUMB, enhance
      the oncogenic phenotypes of OSCC cells. Oncogenic enhancement modulated by miR
      146a expression is attenuated by exogenous IRAK1 or NUMB expression. This study
      shows that miR-146a expression contributes to oral carcinogenesis by targeting
      the IRAK1, TRAF6 and NUMB genes. 

PMID- 24302992
TI  - Spatial hyperschematia without spatial neglect after insulo-thalamic
      disconnection.
AB  - Different spatial representations are not stored as a single multipurpose map in
      the brain. Right brain-damaged patients can show a distortion, a compression of
      peripersonal and extrapersonal space. Here we report the case of a patient with a
      right insulo-thalamic disconnection without spatial neglect. The patient,
      compared with 10 healthy control subjects, showed a constant and reliable
      increase of her peripersonal and extrapersonal egocentric space representations -
      that we named spatial hyperschematia - yet left her allocentric space
      representations intact. This striking dissociation shows that our interactions
      with the surrounding world are represented and processed modularly in the human
      brain, depending on their frame of reference. 

PMID- 24302993
TI  - Continuous and high-intensity interval training: which promotes higher pleasure?
AB  - OBJECTIVES: To compare the psychological responses to continuous (CT) and high
      intensity interval training (HIT) sessions. METHODS: Fifteen men attended one CT
      session and one HIT session. During the first visit, the maximum heart rate,
      VO2Peak and respiratory compensation point (RCP) were determined through a
      maximal cardiopulmonary exercise test. The HIT stimulus intensity corresponded to
      100% of VO2Peak, and the average intensity of both sessions was maintained at 15%
      below the RCP. The order of the sessions was randomized. Psychological and
      physiological variables were recorded before, during and after each session.
      RESULTS: There were no significant differences between the average percentages of
      VO2 during the two exercise sessions (HIT: 73.3% vs. CT: 71.8%; p = 0.779). Lower
      responses on the feeling scale (p<=0.01) and higher responses on the felt arousal
      scale (p<=0.001) and the rating of perceived exertion were obtained during the
      HIT session. Despite the more negative feeling scale responses observed during
      HIT and a greater feeling of fatigue (measured by Profile of Mood States)
      afterwards (p<0.01), the physical activity enjoyment scale was not significantly
      different between the two conditions (p = 0.779). CONCLUSION: Despite the same
      average intensity for both conditions, similar psychological responses under HIT
      and CT conditions were not observed, suggesting that the higher dependence on
      anaerobic metabolism during HIT negatively influenced the feeling scale
      responses.

PMID- 24302994
TI  - A novel approach for prediction of vitamin d status using support vector
      regression.
AB  - BACKGROUND: Epidemiological evidence suggests that vitamin D deficiency is linked
      to various chronic diseases. However direct measurement of serum 25
      hydroxyvitamin D (25(OH)D) concentration, the accepted biomarker of vitamin D
      status, may not be feasible in large epidemiological studies. An alternative
      approach is to estimate vitamin D status using a predictive model based on
      parameters derived from questionnaire data. In previous studies, models developed
      using Multiple Linear Regression (MLR) have explained a limited proportion of the
      variance and predicted values have correlated only modestly with measured values.
      Here, a new modelling approach, nonlinear radial basis function support vector
      regression (RBF SVR), was used in prediction of serum 25(OH)D concentration.
      Predicted scores were compared with those from a MLR model. METHODS: Determinants
      of serum 25(OH)D in Caucasian adults (n = 494) that had been previously
      identified were modelled using MLR and RBF SVR to develop a 25(OH)D prediction
      score and then validated in an independent dataset. The correlation between
      actual and predicted serum 25(OH)D concentrations was analysed with a Pearson
      correlation coefficient. RESULTS: Better correlation was observed between
      predicted scores and measured 25(OH)D concentrations using the RBF SVR model in
      comparison with MLR (Pearson correlation coefficient: 0.74 for RBF SVR; 0.51 for
      MLR). The RBF SVR model was more accurately able to identify individuals with
      lower 25(OH)D levels (<75 nmol/L). CONCLUSION: Using identical determinants, the
      RBF SVR model provided improved prediction of serum 25(OH)D concentrations and
      vitamin D deficiency compared with a MLR model, in this dataset.

PMID- 24302995
TI  - Spatial genetic heterogeneity in populations of a newly invasive whitefly in
      china revealed by a nation-wide field survey.
AB  - BACKGROUND: Even though introductions of exotic species provide ready-made
      experiments of rapid evolution, few studies have examined the genetic structure
      of an exotic species shortly after its initial introduction and subsequent
      spread. To determine the genetic structure of its populations during the initial
      introduction, we investigated the invasive sweet potato whitefly (Bemisia tabaci
      Q, commonly known as B. tabaci biotype Q) in China, which was introduced in
      approximately 2003. A total of 619 B. tabaci Q individuals in 20 provinces
      throughout China were collected and analyzed using five microsatellite loci.
      RESULTS: The introduced populations of B. tabaci Q in China represent eight
      genetic clusters with different geographic distributions. The populations in
      Yunnan Province, where B. tabaci Q was first detected, are genetically different
      from the other populations in China. CONCLUSION: The introduced populations of B.
      tabaci Q in China have high spatial genetic heterogeneity. Additional research is
      required to determine whether the heterogeneity results from multiple
      introductions, rapid evolution following one or few introductions, or some
      combination of multiple introductions and rapid evolution. The heterogeneity,
      however, is inconsistent with a single introduction at Yunnan Province, where B.
      tabaci Q was first detected, followed by spread.

PMID- 24302996
TI  - De novo design and synthesis of ultra-short peptidomimetic antibiotics having
      dual antimicrobial and anti-inflammatory activities.
AB  - BACKGROUND: Much attention has been focused on the design and synthesis of
      potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial
      and anti-inflammatory activities. However, their development into therapeutic
      agents has been limited mainly due to their large size (12 to 50 residues in
      length) and poor protease stability. METHODOLOGY/PRINCIPAL FINDINGS: In an
      attempt to overcome the issues described above, a set of ultra-short, His-derived
      antimicrobial peptides (HDAMPs) has been developed for the first time. Through
      systematic tuning of pendant hydrophobic alkyl tails at the N(pi)- and N(tau)
      positions on His, and the positive charge of Arg, much higher prokaryotic
      selectivity was achieved, compared to human AMP LL-37. Additionally, the most
      potent HDAMPs showed promising dual antimicrobial and anti-inflammatory
      activities, as well as anti-methicillin-resistant Staphylococcus aureus (MRSA)
      activity and proteolytic resistance. Our results from transmission electron
      microscopy, membrane depolarization, confocal laser-scanning microscopy, and
      calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via
      dissipation of the membrane potential by forming pore/ion channels on bacterial
      cell membranes. CONCLUSION/SIGNIFICANCE: The combination of the ultra-short size,
      high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory
      activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6
      makes these molecules promising candidates for future antimicrobial therapeutics.

PMID- 24302997
TI  - Magnetic resonance angiography signal intensity as a marker of hemodynamic
      impairment in intracranial arterial stenosis.
AB  - BACKGROUND: Intracranial arterial stenosis (ICAS) is the predominant cause of
      ischemic stroke and transient ischemic attack in Asia. Change of signal
      intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may
      reflect its hemodynamic severity. METHODS: In-patients with a symptomatic single
      ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline
      and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean
      post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background
      SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS.
      Acute infarct volume was measured on baseline diffusion-weighted images (DWI).
      Relationships between SIR and baseline characteristics as well as 1y outcomes
      were evaluated. RESULTS: Thirty-six subjects (86.1% males, mean age 55.0) were
      recruited. Overall, mean SIR was 0.84+/-0.23. Mean SIRs were not significantly
      different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%)
      anatomically moderate stenoses (0.80+/-0.23 versus 0.92+/-0.21, p = 0.126). SIR
      was significantly, linearly and negatively correlated to acute infarct volume on
      DWI (Spearman correlation coefficient -0.471, p = 0.011). Two patients (5.6%) had
      recurrent ischemic strokes at 1y, not related to SIR values. CONCLUSIONS: Change
      of signal intensities across an ICAS on MRA may reflect its hemodynamic and
      functional severity. Future studies are warranted to further verify the
      relationships between this index and prognosis of patients with symptomatic ICAS.

PMID- 24302998
TI  - Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak
      type 2 syndrome is associated to natural killer and natural killer T cell
      defects.
AB  - Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary
      immune deficiency caused by mutations on beta3A gene (AP3B1 gene). The defect
      results in the impairment of the adaptor protein 3 (AP-3) complex, responsible
      for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism,
      bleeding disorders and immunodeficiency. We have studied peripheral blood and
      lymph node biopsies from two siblings affected by HPS2. Lymph node histology
      showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both
      HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an
      increased amount of perforin (Prf) + suggesting a defect in the release of this
      granules-associated protein. By analyzing peripheral blood immune cells we found
      a significant reduction of circulating NKT cells and of CD56(bright)CD16(-)
      Natural Killer (NK) cells subset. Functionally, NK cells were defective in their
      cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as
      in IFN-gamma production. This defect was associated with increased baseline level
      of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK
      cells. In summary, these results suggest that a combined and profound defect of
      innate and adaptive effector cells might explain the susceptibility to infections
      and lymphoma in these HPS2 patients. 

PMID- 24303000
TI  - The effect of PPE-induced emphysema and chronic LPS-induced pulmonary
      inflammation on atherosclerosis development in APOE*3-LEIDEN mice.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      pulmonary inflammation, airways obstruction and emphysema, and is a risk factor
      for cardiovascular disease (CVD). However, the contribution of these individual
      COPD components to this increased risk is unknown. Therefore, the aim of this
      study was to determine the contribution of emphysema in the presence or absence
      of pulmonary inflammation to the increased risk of CVD, using a mouse model for
      atherosclerosis. Because smoke is a known risk factor for both COPD and CVD,
      emphysema was induced by intratracheal instillation of porcine pancreatic
      elastase (PPE). METHODS: Hyperlipidemic APOE*3-Leiden mice were intratracheally
      instilled with vehicle, 15 or 30 ug PPE and after 4 weeks, mice received a
      Western-type diet (WTD). To study the effect of emphysema combined with pulmonary
      inflammation on atherosclerosis, mice received 30 ug PPE and during WTD feeding,
      mice were intranasally instilled with vehicle or low-dose lipopolysaccharide
      (LPS; 1 ug/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and
      emphysema, pulmonary inflammation and atherosclerosis were analysed. RESULTS:
      Intratracheal PPE administration resulted in a dose-dependent increase in
      emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment.
      Additional low-dose intranasal LPS administration induced a low-grade systemic IL
      6 response, as compared to vehicle. Combining intratracheal PPE with intranasal
      LPS instillation significantly increased the number of pulmonary macrophages and
      neutrophils. Plasma lipids during the study were not different. LPS instillation
      caused a limited, but significant increase in the atherosclerotic lesion area.
      This increase was not further enhanced by PPE. CONCLUSION: This study shows for
      the first time that PPE-induced emphysema both in the presence and absence of
      pulmonary inflammation does not affect atherosclerotic lesion development.

PMID- 24302999
TI  - Next-generation sequencing-based transcriptome analysis of Helicoverpa armigera
      Larvae immune-primed with Photorhabdus luminescens TT01.
AB  - Although invertebrates are incapable of adaptive immunity, immunal reactions
      which are functionally similar to the adaptive immunity of vertebrates have been
      described in many studies of invertebrates including insects. The phenomenon was
      termed immune priming. In order to understand the molecular mechanism of immune
      priming, we employed Illumina/Solexa platform to investigate the transcriptional
      changes of the hemocytes and fat body of Helicoverpa armigera larvae immune
      primed with the pathogenic bacteria Photorhabdus luminescens TT01. A total of
      43.6 and 65.1 million clean reads with 4.4 and 6.5 gigabase sequence data were
      obtained from the TT01 (the immune-primed) and PBS (non-primed) cDNA libraries
      and assembled into 35,707 all-unigenes (non-redundant transcripts), which has a
      length varied from 201 to 16,947 bp and a N50 length of 1,997 bp. For 35,707 all
      unigenes, 20,438 were functionally annotated and 2,494 were differentially
      expressed after immune priming. The differentially expressed genes (DEGs) are
      mainly related to immunity, detoxification, development and metabolism of the
      host insect. Analysis on the annotated immune related DEGs supported a hypothesis
      that we proposed previously: the immune priming phenomenon observed in H.
      armigera larvae was achieved by regulation of key innate immune elements. The
      transcriptome profiling data sets (especially the sequences of 1,022 unannotated
      DEGs) and the clues (such as those on immune-related signal and regulatory
      pathways) obtained from this study will facilitate immune-related novel gene
      discovery and provide valuable information for further exploring the molecular
      mechanism of immune priming of invertebrates. All these will increase our
      understanding of invertebrate immunity which may provide new approaches to
      control insect pests or prevent epidemic of infectious diseases in economic
      invertebrates in the future. 

PMID- 24303001
TI  - Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African
      and European ancestry.
AB  - Variants within the gene cluster encoding alpha3, alpha5, and beta4 nicotinic
      receptor subunits are major risk factors for substance dependence. The strongest
      impact on risk is associated with variation in the CHRNA5 gene, where at least
      two mechanisms are at work: amino acid variation and altered mRNA expression
      levels. The risk allele of the non-synonymous variant (rs16969968; D398N)
      primarily occurs on the haplotype containing the low mRNA expression allele. In
      populations of European ancestry, there are approximately 50 highly correlated
      variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene
      region that are associated with CHRNA5 mRNA levels. It is not clear which of
      these variants contribute to the changes in CHRNA5 transcript level. Because
      populations of African ancestry have reduced linkage disequilibrium among
      variants spanning this gene cluster, eQTL mapping in subjects of African ancestry
      could potentially aid in defining the functional variants that affect CHRNA5 mRNA
      levels. We performed quantitative allele specific gene expression using frontal
      cortices derived from 49 subjects of African ancestry and 111 subjects of
      European ancestry. This method measures allele-specific transcript levels in the
      same individual, which eliminates other biological variation that occurs when
      comparing expression levels between different samples. This analysis confirmed
      that substance dependence associated variants have a direct cis-regulatory effect
      on CHRNA5 transcript levels in human frontal cortices of African and European
      ancestry and identified 10 highly correlated variants, located in a 9 kb region,
      that are potential functional variants modifying CHRNA5 mRNA expression levels. 

PMID- 24303003
TI  - The effects of host diversity on vector-borne disease: the conditions under which
      diversity will amplify or dilute the disease risk.
AB  - Multihost vector-borne infectious diseases form a significant fraction of the
      global infectious disease burden. In this study we explore the relationship
      between host diversity, vector behavior, and disease risk. To this end, we have
      developed a new dynamic model which includes two distinct host species and one
      vector species with variable preferences. With the aid of the model we were able
      to compute the basic reproductive rate, R 0, a well-established measure of
      disease risk that serves as a threshold parameter for disease outbreak. The model
      analysis reveals that the system has two different qualitative behaviors: (i) the
      well-known dilution effect, where the maximal R0 is obtained in a community which
      consists a single host (ii) a new amplification effect, denoted by us as
      diversity amplification, where the maximal R0 is attained in a community which
      consists both hosts. The model analysis extends on previous results by
      underlining the mechanism of both, diversity amplification and the dilution, and
      specifies the exact conditions for their occurrence. We have found that diversity
      amplification occurs where the vector prefers the host with the highest
      transmission ability, and dilution is obtained when the vector does not show any
      preference, or it prefers to bite the host with the lower transmission ability.
      The mechanisms of dilution and diversity amplification are able to account for
      the different and contradictory patterns often observed in nature (i.e., in some
      cases disease risk is increased while in other is decreased when the diversity is
      increased). Implication of the diversity amplification mechanism also challenges
      current premises about the interaction between biodiversity, climate change, and
      disease risk and calls for retrospective thinking in planning intervention
      policies aimed at protecting the preferred host species. 

PMID- 24303002
TI  - A species flock driven by predation? Secondary metabolites support
      diversification of slugs in antarctica.
AB  - Antarctica's rich marine animal biodiversity has been substantially influenced by
      a complex glacial history, but it is unclear why some taxa responded with
      diversification while others did not. Despite being considered a single endemic
      sea slug species in the Southern Ocean, mitochondrial DNA sequencing of Doris
      kerguelenensis (Bergh, 1884) revealed a multitude of highly divergent lineages.
      But because of the uniparental inheritance of mitochondria, it was unclear
      whether those lineages represented a radiation of cryptic species or simply
      stochastic sorting patterns of populations that rarely reach equilibrium. Here we
      demonstrate that the mitochondrial groups in D. kerguelenensis also correlate
      with nuclear DNA. Additionally, by extracting secondary metabolites from the same
      individuals we sequenced, we were also able to directly link the secondary
      metabolome to a mitochondrial lineage. These metabolites are not derived from the
      diet, but instead are synthesized de novo and implicated in an anti-predatory
      role. The strong linkage between these metabolites and the mitochondrial lineages
      strongly suggests that these lineages represent cryptic species in an adaptive
      radiation. Over millions of years, episodic glacial cycles reduced the
      distribution of a formerly widespread slug into a series of small vicariant
      refuges, vulnerable to genetic drift and predation pressure. The recognition of
      this marine invertebrate species flock implicates a strongly synergistic role for
      selection and allopatry driving speciation in this system. 

PMID- 24303004
TI  - Breast milk and gut microbiota in African mothers and infants from an area of
      high HIV prevalence.
AB  - BACKGROUND: Human milk and infant gut microbiota are essential for the immune
      system maturation and protection against infections. There is scarce information
      on the microbiological composition of breast milk in general, and none from
      developing countries. The objective of the study was to characterize the breast
      milk and gut microbiota from mothers and infants from southern Mozambique, where
      infections and breastfeeding are prevalent. METHODS: A community-based study was
      undertaken among 121 pairs of women and infants. Breast milk and infant's faeces
      were analyzed by bacterial culture and molecular methods. Breast milk samples
      were screened for HIV RNA by RT-PCR. RESULTS: The most frequent bacterial groups
      isolated by culture media in breast milk were Staphylococci (96.4%), Streptococci
      (92.7%) and Lactobacilli (56.4%). HIV RNA was detected in 24% of the samples.
      Staphylococcus hominis, S. aureus, and S.parasanguis were more frequently
      isolated in infants <=14 days of life. Women on exclusive breastfeeding presented
      higher proportion of S. parasanguis in breast milk than those on mixed infant
      feeding (36.4% versus 11.1%, p = 0.035). Bacterial diversity (mean number of
      bacterial species isolated by sample: 10.4 versus 8.5; p = 0.004) and the
      frequency of Lactobacillus spp (75.9% versus 36%, p = 0.003) were higher in the
      specimens with HIV RNA than in those without it. The main bacterial groups found
      in infant's faeces were Bifidobacterium, Streptococci and Enterococci.
      CONCLUSIONS: Women with HIV RNA in breast milk had a different pattern of
      microbiological composition, suggesting specific immunopathological phenomena in
      HIV-infected women. Both breast milk and faecal microbiota composition varied
      with lactation period, which might be related to changes in the type of feeding
      over time and/or in the milk's biochemical characteristics. These findings
      provide insights into interactions between commensal bacteria and HIV infection
      in human milk and the role of these bacteria in mucosal protection against
      infections in breastfed infants.

PMID- 24303005
TI  - The influence of N-linked glycans on the molecular dynamics of the HIV-1 gp120 V3
      loop.
AB  - N-linked glycans attached to specific amino acids of the gp120 envelope trimer of
      a HIV virion can modulate the binding affinity of gp120 to CD4, influence
      coreceptor tropism, and play an important role in neutralising antibody
      responses. Because of the challenges associated with crystallising fully
      glycosylated proteins, most structural investigations have focused on describing
      the features of a non-glycosylated HIV-1 gp120 protein. Here, we use a
      computational approach to determine the influence of N-linked glycans on the
      dynamics of the HIV-1 gp120 protein and, in particular, the V3 loop. We compare
      the conformational dynamics of a non-glycosylated gp120 structure to that of two
      glycosylated gp120 structures, one with a single, and a second with five,
      covalently linked high-mannose glycans. Our findings provide a clear illustration
      of the significant effect that N-linked glycosylation has on the temporal and
      spatial properties of the underlying protein structure. We find that glycans
      surrounding the V3 loop modulate its dynamics, conferring to the loop a marked
      propensity towards a more narrow conformation relative to its non-glycosylated
      counterpart. The conformational effect on the V3 loop provides further support
      for the suggestion that N-linked glycosylation plays a role in determining HIV-1
      coreceptor tropism. 

PMID- 24303006
TI  - Gene expression signature of normal cell-of-origin predicts ovarian tumor
      outcomes.
AB  - The potential role of the cell-of-origin in determining the tumor phenotype has
      been raised, but not adequately examined. We hypothesized that distinct cells-of
      origin may play a role in determining ovarian tumor phenotype and outcome. Here
      we describe a new cell culture medium for in vitro culture of paired normal human
      ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer.
      While these cells have been cultured individually for short periods of time, to
      our knowledge this is the first long-term culture of both cell types from the
      same donors. Through analysis of the gene expression profiles of the cultured
      OV/FT cells we identified a normal cell-of-origin gene signature that classified
      primary ovarian cancers into OV-like and FT-like subgroups; this classification
      correlated with significant differences in clinical outcomes. The identification
      of a prognostically significant gene expression signature derived solely from
      normal untransformed cells is consistent with the hypothesis that the normal cell
      of-origin may be a source of ovarian tumor heterogeneity and the associated
      differences in tumor outcome. 

PMID- 24303009
TI  - Evaluation of five candidate genes from GWAS for association with oligozoospermia
      in a Han Chinese population.
AB  - BACKGROUND: Oligozoospermia is one of the severe forms of idiopathic male
      infertility. However, its pathology is largely unknown, and few genetic factors
      have been defined. Our previous genome-wide association study (GWAS) has
      identified four risk loci for non-obstructive azoospermia (NOA). OBJECTIVE: To
      investigate the potentially functional genetic variants (including not only
      common variants, but also less-common and rare variants) of these loci on
      spermatogenic impairment, especially oligozoospermia. DESIGN SETTING AND
      PARTICIPANTS: A total of 784 individuals with oligozoospermia and 592 healthy
      controls were recruited to this study from March 2004 and January 2011.
      MEASUREMENTS: We conducted a two-stage study to explore the association between
      oligozoospermia and new makers near NOA risk loci. In the first stage, we used
      next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy
      controls to screen oligozoospermia-susceptible genetic variants. Next, we
      validated these variants in a large cohort containing 688 cases and 496 controls
      by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.
      RESULTS AND LIMITATIONS: Totally, we observed seven oligozoospermia associated
      variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5,
      rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage.
      In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were
      associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62
      (P  =  0.005, 95%CI 1.58-13.4) and 1.82 (P  =  0.005, 95%CI 1.01-1.64),
      respectively. Further investigation in larger populations and functional
      characterizations are needed to validate our findings. CONCLUSIONS: Our study
      provides evidence of independent oligozoospermia risk alleles driven by variants
      in the potentially functional regions of genes discovered by GWAS. Our findings
      suggest that integrating sequence data with large-scale genotyping will serve as
      an effective strategy for discovering risk alleles in the future.

PMID- 24303008
TI  - The gastric CB1 receptor modulates ghrelin production through the mTOR pathway to
      regulate food intake.
AB  - Over the years, the knowledge regarding the relevance of the cannabinoid system
      to the regulation of metabolism has grown steadily. A central interaction between
      the cannabinoid system and ghrelin has been suggested to regulate food intake.
      Although the stomach is the main source of ghrelin and CB1 receptor expression in
      the stomach has been described, little information is available regarding the
      possible interaction between the gastric cannabinoid and ghrelin systems in the
      integrated control of energy homeostasis. The main objective of the present work
      was to assess the functional interaction between these two systems in terms of
      food intake using a combination of in vivo and in vitro approaches. The present
      work demonstrates that the peripheral blockade of the CB1 receptor by rimonabant
      treatment decreased food intake but only in food-deprived animals. This
      anorexigenic effect is likely a consequence of decreases in gastric ghrelin
      secretion induced by the activation of the mTOR/S6K1 intracellular pathway in the
      stomach following treatment with rimonabant. In support of this supposition,
      animals in which the mTOR/S6K1 intracellular pathway was blocked by chronic
      rapamycin treatment, rimonabant had no effect on ghrelin secretion. Vagal
      communication may also be involved because rimonabant treatment was no longer
      effective when administered to animals that had undergone surgical vagotomy. In
      conclusion, to the best of our knowledge, the present work is the first to
      describe a CB1 receptor-mediated mechanism that influences gastric ghrelin
      secretion and food intake through the mTOR pathway. 

PMID- 24303007
TI  - Beclin 1 deficiency correlated with lymph node metastasis, predicts a distinct
      outcome in intrahepatic and extrahepatic cholangiocarcinoma.
AB  - Autophagy can be tumor suppressive as well as promotive in regulation of
      tumorigenesis and disease progression. Accordingly, the prognostic significance
      of autophagy key regulator Beclin 1 was varied among different tumors. Here, we
      detected the clinicopathological and prognostic effect of Beclin 1 in the
      subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic
      cholangiocarcinoma (ECC). Beclin 1 expression level was detected by
      immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that
      Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of
      72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node
      metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012).
      However, we did not detect any correlations between Beclin 1 and other
      clinicopathological features, including tumor subtypes, vascular invasion, HBV
      infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis
      showed that, compared with the high expression subset, Beclin 1 low expression
      was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS
      46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and
      multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior
      PFS as well as overall survival than ECC, particularly than that of Beclin 1
      highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low
      expression, correlated with lymph node metastasis, and might be a negative
      prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the
      anatomical location might lead to refined prognosis for the subtypes of ICC and
      ECC. 

PMID- 24303010
TI  - Katanin p60 contributes to microtubule instability around the midbody and
      facilitates cytokinesis in rat cells.
AB  - The completion of cytokinesis is crucial for mitotic cell division. Cleavage
      furrow ingression is followed by the breaking and resealing of the intercellular
      bridge, but the detailed mechanism underlying this phenomenon remains unknown.
      Katanin is a microtubule-severing protein comprised of an AAA ATPase subunit and
      an accessory subunit designated as p60 and p80, respectively. Localization of
      katanin p60 was observed at the midzone to midbody from anaphase to cytokinesis
      in rat cells, and showed a ring-shaped distribution in the gap between the inside
      of the contractile ring and the central spindle bundle in telophase. Katanin p60
      did not bind with p80 at the midzone or midbody, and localization was shown to be
      dependent on microtubules. At the central spindle and the midbody, no microtubule
      growth plus termini were seen with katanin p60, and microtubule density was
      inversely correlated with katanin p60 density in the region of katanin p60
      localization that seemed to lead to microtubule destabilization at the midbody.
      Inhibition of katanin p60 resulted in incomplete cytokinesis by regression and
      thus caused the appearance of binucleate cells. These results suggest that
      katanin p60 contributes to microtubule instability at the midzone and midbody and
      facilitates cytokinesis in rat cells. 

PMID- 24303011
TI  - Functional reconstitution of Staphylococcus aureus truncated AgrC histidine
      kinase in a model membrane system.
AB  - The integral membrane protein AgrC is a histidine kinase whose sensor domains
      interact with an autoinducing peptide, resulting in a series of downstream
      responses. In this study, truncated AgrCTM5-6C and AgrCTM5-6C-GFP with GFP as a
      reporter gene were produced using a bacterial system. Purified AgrCTM5-6C and
      AgrCTM5-6C-GFP were reconstituted into liposomes by a detergent-mediated method.
      To achieve high-yield protein incorporation, we investigated the effect of
      different detergents on protein reconstitution efficiency. The highest
      incorporation was found with N,N-dimethyldode-cylamine N-oxide during complete
      liposome solubilization, which resulted in a yield of 85+/-5%. The COOH-terminus
      of the protein AgrCTM5-6C was almost exclusively oriented towards the inside of
      the vesicles. AgrCTM5-6C in proteoliposomes exhibited approximately a 6-fold
      increase in constitutive activity compared with AgrCTM5-6C in detergent micelles.
      The reconstitution of AgrCTM5-6C or AgrCTM5-6C-GFP was characterized using
      dynamic light scattering, fluorescence microscopy, and transmission electron
      microscopy. Based on the results, the optimal conditions for protein
      incorporation were defined. These findings contribute to the study of membrane
      protein structure and function in vitro using a reconstitution system. 

PMID- 24303012
TI  - High-resolution mass spectrometry driven discovery of peptidic danger signals in
      insect immunity.
AB  - The 'danger model' is an alternative concept for immune response postulating that
      the immune system reacts to entities that do damage (danger associated molecular
      patterns, DAMP) and not only to entities that are foreign (pathogen-associated
      molecular patterns, PAMP) as proposed by classical immunology concepts. In this
      study we used Galleria mellonella to validate the danger model in insects.
      Hemolymph of G. mellonella was digested with thermolysin (as a representative for
      virulence-associated metalloproteinases produced by humanpathogens) followed by
      chromatographic fractionation. Immune-stimulatory activity was tested by
      measuring lysozyme activity with the lytic zone assays against Micrococcus luteus
      cell wall components. Peptides were analyzed by nano-scale liquid chromatography
      coupled to high-resolution Fourier transform mass spectrometers. Addressing the
      lack of a genome sequence we complemented the rudimentary NCBI protein database
      with a recently established transcriptome and de novo sequencing methods for
      peptide identification. This approach led to identification of 127 peptides, 9 of
      which were identified in bioactive fractions. Detailed MS/MS experiments in
      comparison with synthetic analogues confirmed the amino acid sequence of all 9
      peptides. To test the potential of these putative danger signals to induce immune
      responses we injected the synthetic analogues into G. mellonella and monitored
      the anti-bacterial activity against living Micrococcus luteus. Six out of 9
      peptides identified in the bioactive fractions exhibited immune-stimulatory
      activity when injected. Hence, we provide evidence that small peptides resulting
      from thermolysin-mediated digestion of hemolymph proteins function as endogenous
      danger signals which can set the immune system into alarm. Consequently, our
      study indicates that the danger model also plays a role in insect immunity. 

PMID- 24303014
TI  - Targeting tissular immune response improves diagnostic performance of anti
      Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease.
AB  - Antibodies against Saccharomyces cerevisiae (ASCA) and Escherichia coli outer
      membrane porin C (anti-OmpC) are known to be detectable in the serum of patients
      with Crohn's disease (CD) but display a very poor sensitivity for the disease
      especially in forms with isolated colonic involvement. In this study we aimed at
      evaluating performances of these markers in supernatant of cultured colonic
      biopsies. Patients with colonic CD (n =  67), ulcerative colitis (UC) (n = 35)
      and control individuals (n = 37) were prospectively recruited for colonoscopy
      pinch biopsies and blood sampling. Serum and supernatant of culture tissues were
      analyzed for ASCA and anti-OmpC. Direct immunofluorescence was also performed on
      colonic tissues for total IgA detection. We detected for the first time ASCA
      IgA/IgG and anti-OmpC IgA in cultured colonic tissue supernatants. For both
      markers, sensitivities for diagnosing CD were better in supernatants (ASCA:
      53.7%, anti-OmpC: 28.4%) than in serum (ASCA: 31.3%, anti-OmpC: 22.4%).
      Combination of results from a panel of these tests gave the greatest sensitivity
      ever described for CD diagnosis in colonic forms (70.2%). In this study, we
      described, for the first time, ASCA in supernatant of colonic tissue cultures.
      This assaying approach in CD diagnosis should be taken into consideration in the
      future especially in CD forms with isolated colonic involvement. 

PMID- 24303013
TI  - A point mutation in the gene for asparagine-linked glycosylation 10B (Alg10b)
      causes nonsyndromic hearing impairment in mice (Mus musculus).
AB  - The study of mouse hearing impairment mutants has led to the identification of a
      number of human hearing impairment genes and has greatly furthered our
      understanding of the physiology of hearing. The novel mouse mutant
      neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent
      startle response to sound and is therefore a potential murine model of human
      hearing impairment. Genetic analysis of 500 intercross progeny localized the
      mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense
      mutation in a highly-conserved amino acid was found in the asparagine-linked
      glycosylation 10B gene (Alg10b), which is within the critical interval for the
      nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene
      rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the
      mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous
      nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion
      product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs).
      Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs
      also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype
      Alg10b transgene. These results suggested a defect in the outer hair cells of
      mutant animals, which was confirmed by histologic analysis. This is the first
      report of mutation in a gene involved in the asparagine (N)-linked glycosylation
      pathway causing nonsyndromic hearing impairment, and it suggests that the hearing
      apparatus, and the outer hair cells in particular, are exquisitely sensitive to
      perturbations of the N-linked glycosylation pathway. 

PMID- 24303015
TI  - Dynamic artificial neural networks with affective systems.
AB  - Artificial neural networks (ANNs) are processors that are trained to perform
      particular tasks. We couple a computational ANN with a simulated affective system
      in order to explore the interaction between the two. In particular, we design a
      simple affective system that adjusts the threshold values in the neurons of our
      ANN. The aim of this paper is to demonstrate that this simple affective system
      can control the firing rate of the ensemble of neurons in the ANN, as well as to
      explore the coupling between the affective system and the processes of long term
      potentiation (LTP) and long term depression (LTD), and the effect of the
      parameters of the affective system on its performance. We apply our networks with
      affective systems to a simple pole balancing example and briefly discuss the
      effect of affective systems on network performance. 

PMID- 24303016
TI  - Survivin expression and prognostic significance in pediatric malignant peripheral
      nerve sheath tumors (MPNST).
AB  - Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies
      comprising approximately 5-10% of all soft tissue sarcomas. In this study, we
      focused on pediatric MPNST arising in the first 2 decades of life, as they
      represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in
      children. In MPNST, several genetic alterations affect the chromosomal region 17q
      encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin
      has been found to be an effective marker for cancer detection and outcome
      prediction, we analyzed survivin expression in 35 tumor samples derived from
      young patients affected by sporadic and neurofibromatosis type 1-associated
      MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and
      immunohistochemical staining, respectively, while gene amplification was analyzed
      by FISH. Data were correlated with the clinicopathological characteristics of
      patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a
      copy number gain of BIRC5; furthermore, increased levels of transcripts
      correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067),
      and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these
      data support the concept that survivin can be regarded as a useful prognostic
      marker for pediatric MPNST and a promising target for therapeutic interventions. 

PMID- 24303017
TI  - Whole-organ CT perfusion of the pancreas: impact of iterative reconstruction on
      image quality, perfusion parameters and radiation dose in 256-slice CT
      preliminary findings.
AB  - BACKGROUND: This study was performed to assess whether iterative reconstruction
      can reduce radiation dose while maintaining acceptable image quality, and to
      investigate whether perfusion parameters vary from conventional filtered back
      projection (FBP) at the low-tube-voltage (80-kVp) during whole-pancreas perfusion
      examination using a 256-slice CT. METHODS: 76 patients with known or suspected
      pancreatic mass underwent whole-pancreas perfusion by a 256-slice CT. High- and
      low-tube-voltage CT images were acquired. 120-kVp image data (protocol A) and 80
      kVp image data (protocol B) were reconstructed with conventional FBP, and 80-kVp
      image data were reconstructed with iDose(4) (protocol C) iterative
      reconstruction. The image noise; contrast-to-noise ratio (CNR) relative to muscle
      for the pancreas, liver, and aorta; and radiation dose of each protocol were
      assessed quantitatively. Overall image quality was assessed qualitatively. Among
      76 patients, 23 were eventually proven to have a normal pancreas. Perfusion
      parameters of normal pancreas in each protocol including blood volume, blood
      flow, and permeability-surface area product were measured. RESULTS: In the
      quantitative study, protocol C reduced image noise by 36.8% compared to protocol
      B (P<0.001). Protocol C yielded significantly higher CNR relative to muscle for
      the aorta, pancreas and liver compared to protocol B (P<0.001), and offered no
      significant difference compared to protocol A. In the qualitative study,
      protocols C and A gained similar scores and protocol B gained the lowest score
      for overall image quality (P<0.001). Mean effective doses were 23.37 mSv for
      protocol A and 10.81 mSv for protocols B and C. There were no significant
      differences in the normal pancreas perfusion values among three different
      protocols. CONCLUSION: Low-tube-voltage and iDose(4) iterative reconstruction can
      dramatically decrease the radiation dose with acceptable image quality during
      whole-pancreas CT perfusion and have no significant impact on the perfusion
      parameters of normal pancreas compared to the conventional FBP reconstruction
      using a 256-slice CT scanner.

PMID- 24303018
TI  - Characterization of light lesion paradigms and optical coherence tomography as
      tools to study adult retina regeneration in zebrafish.
AB  - Light-induced lesions are a powerful tool to study the amazing ability of
      photoreceptors to regenerate in the adult zebrafish retina. However, the
      specificity of the lesion towards photoreceptors or regional differences within
      the retina are still incompletely understood. We therefore characterized the
      process of degeneration and regeneration in an established paradigm, using
      intense white light from a fluorescence lamp on swimming fish (diffuse light
      lesion). We also designed a new light lesion paradigm where light is focused
      through a microscope onto the retina of an immobilized fish (focused light
      lesion). Focused light lesion has the advantage of creating a locally restricted
      area of damage, with the additional benefit of an untreated control eye in the
      same animal. In both paradigms, cell death is observed as an immediate early
      response, and proliferation is initiated around 2 days post lesion (dpl), peaking
      at 3 dpl. We furthermore find that two photoreceptor subtypes (UV and blue
      sensitive cones) are more susceptible towards intense white light than red/green
      double cones and rods. We also observed specific differences within light
      lesioned areas with respect to the process of photoreceptor degeneration: UV cone
      debris is removed later than any other type of photoreceptor in light lesions.
      Unspecific damage to retinal neurons occurs at the center of a focused light
      lesion territory, but not in the diffuse light lesion areas. We simulated the
      fish eye optical properties using software simulation, and show that the optical
      properties may explain the light lesion patterns that we observe. Furthermore, as
      a new tool to study retinal degeneration and regeneration in individual fish in
      vivo, we use spectral domain optical coherence tomography. Collectively, the
      light lesion and imaging assays described here represent powerful tools for
      studying degeneration and regeneration processes in the adult zebrafish retina. 

PMID- 24303019
TI  - Detecting protein candidate fragments using a structural alphabet profile
      comparison approach.
AB  - Predicting accurate fragments from sequence has recently become a critical step
      for protein structure modeling, as protein fragment assembly techniques are
      presently among the most efficient approaches for de novo prediction. A key step
      in these approaches is, given the sequence of a protein to model, the
      identification of relevant fragments - candidate fragments - from a collection of
      the available 3D structures. These fragments can then be assembled to produce a
      model of the complete structure of the protein of interest. The search for
      candidate fragments is classically achieved by considering local sequence
      similarity using profile comparison, or threading approaches. In the present
      study, we introduce a new profile comparison approach that, instead of using
      amino acid profiles, is based on the use of predicted structural alphabet
      profiles, where structural alphabet profiles contain information related to the
      3D local shapes associated with the sequences. We show that structural alphabet
      profile-profile comparison can be used efficiently to retrieve accurate
      structural fragments, and we introduce a fully new protocol for the detection of
      candidate fragments. It identifies fragments specific of each position of the
      sequence and of size varying between 6 and 27 amino-acids. We find it outperforms
      present state of the art approaches in terms (i) of the accuracy of the fragments
      identified, (ii) the rate of true positives identified, while having a high
      coverage score. We illustrate the relevance of the approach on complete target
      sets of the two previous Critical Assessment of Techniques for Protein Structure
      Prediction (CASP) rounds 9 and 10. A web server for the approach is freely
      available at http://bioserv.rpbs.univ-paris-diderot.fr/SAFrag. 

PMID- 24303020
TI  - Insights from the complete chloroplast genome into the evolution of Sesamum
      indicum L.
AB  - Sesame (Sesamum indicum L.) is one of the oldest oilseed crops. In order to
      investigate the evolutionary characters according to the Sesame Genome Project,
      apart from sequencing its nuclear genome, we sequenced the complete chloroplast
      genome of S. indicum cv. Yuzhi 11 (white seeded) using Illumina and 454
      sequencing. Comparisons of chloroplast genomes between S. indicum and the 18
      other higher plants were then analyzed. The chloroplast genome of cv. Yuzhi 11
      contains 153,338 bp and a total of 114 unique genes (KC569603). The number of
      chloroplast genes in sesame is the same as that in Nicotiana tabacum, Vitis
      vinifera and Platanus occidentalis. The variation in the length of the large
      single-copy (LSC) regions and inverted repeats (IR) in sesame compared to 18
      other higher plant species was the main contributor to size variation in the cp
      genome in these species. The 77 functional chloroplast genes, except for ycf1 and
      ycf2, were highly conserved. The deletion of the cp ycf1 gene sequence in cp
      genomes may be due either to its transfer to the nuclear genome, as has occurred
      in sesame, or direct deletion, as has occurred in Panax ginseng and Cucumis
      sativus. The sesame ycf2 gene is only 5,721 bp in length and has lost about 1,179
      bp. Nucleotides 1-585 of ycf2 when queried in BLAST had hits in the sesame draft
      genome. Five repeats (R10, R12, R13, R14 and R17) were unique to the sesame
      chloroplast genome. We also found that IR contraction/expansion in the cp genome
      alters its rate of evolution. Chloroplast genes and repeats display the signature
      of convergent evolution in sesame and other species. These findings provide a
      foundation for further investigation of cp genome evolution in Sesamum and other
      higher plants. 

PMID- 24303022
TI  - Feeding preferences of abyssal macrofauna inferred from in situ pulse chase
      experiments.
AB  - Climatic fluctuations may significantly alter the taxonomic and biochemical
      composition of phytoplankton blooms and subsequently phytodetritus, the food
      source for the majority of deep-sea communities. To examine the response of
      abyssal benthic communities to different food resources we simulated a food
      sedimentation event containing diatoms and coccolithophorids at Station M in the
      NE Pacific. In one set of experiments we measured incorporation of diatomC and
      coccoN into the macrofauna using isotopically enriched (13)C-diatoms and (15)N
      coccolithophores. In a second experiment we measured incorporation of C and N
      from dual-labelled ((13)C and (15)N) diatoms. The second experiment was repeated
      2 months later to assess the effect of seasonality. The simulated food pulses
      represented additions of 650 - 800 mg C m(-2) and 120 mg N m(-2) to the seafloor.
      In all cases rapid incorporation of tracer was observed within 4 days, with
      between 20% and 52% of the macrofauna displaying evidence of enrichment. However,
      incorporation levels of both diatomC and coccoN were low (<0.05% and 0.005% of
      the added C and N). Incorporation of labelled diatoms was similar during both
      June and September suggesting that the community was not food limited during
      either period. We found no evidence for selective ingestion of the different food
      types in the metazoan fauna suggesting that macrofauna do not have strong
      preferences for diatom vs. coccolithophore dominated phytodetrital pulses. C?N
      ratios from both experiments suggest that the metazoan macrofauna community
      appear to have higher C demands and/or assimilation efficiencies compared to N.
      Concomitantly, the foraminifera preferentially selected for diatomN over coccoN,
      and we suggest that this may be related to foraminiferal requirements for
      intracellular nitrate. These experiments provide evidence that abyssal faunal
      feeding strategies are in part driven by an organism's internal stoichiometric
      budgets and biochemical requirements. 

PMID- 24303021
TI  - Regulation of abiotic stress signalling by Arabidopsis C-terminal domain
      phosphatase-like 1 requires interaction with a k-homology domain-containing
      protein.
AB  - Arabidopsis thaliana CARBOXYL-TERMINAL DOMAIN (CTD) PHOSPHATASE-LIKE 1 (CPL1)
      regulates plant transcriptional responses to diverse stress signals. Unlike
      typical CTD phosphatases, CPL1 contains two double-stranded (ds) RNA binding
      motifs (dsRBMs) at its C-terminus. Some dsRBMs can bind to dsRNA and/or other
      proteins, but the function of the CPL1 dsRBMs has remained obscure. Here, we
      report identification of REGULATOR OF CBF GENE EXPRESSION 3 (RCF3) as a CPL1
      interacting protein. RCF3 co-purified with tandem-affinity-tagged CPL1 from
      cultured Arabidopsis cells and contains multiple K-homology (KH) domains, which
      were predicted to be important for binding to single-stranded DNA/RNA. Yeast two
      hybrid, luciferase complementation imaging, and bimolecular fluorescence
      complementation analyses established that CPL1 and RCF3 strongly associate in
      vivo, an interaction mediated by the dsRBM1 of CPL1 and the KH3/KH4 domains of
      RCF3. Mapping of functional regions of CPL1 indicated that CPL1 in vivo function
      requires the dsRBM1, catalytic activity, and nuclear targeting of CPL1. Gene
      expression profiles of rcf3 and cpl1 mutants were similar during iron deficiency,
      but were distinct during the cold response. These results suggest that tethering
      CPL1 to RCF3 via dsRBM1 is part of the mechanism that confers specificity to CPL1
      mediated transcriptional regulation. 

PMID- 24303023
TI  - Transformation of sexually transmitted infection-causing serovars of chlamydia
      trachomatis using Blasticidin for selection.
AB  - Plasmid-free Chlamydia trachomatis serovar L2 organisms have been transformed
      with chlamydial plasmid-based shuttle vectors pGFP::SW2 and pBRCT using beta
      lactamase as a selectable marker. However, the recommendation of amoxicillin, a
      beta-lactam antibiotics, as one of the choices for treating pregnant women with
      cervicitis due to C. trachomatis infection has made the existing shuttle vectors
      unsuitable for transforming sexually transmitted infection (STI)-causing serovars
      of C. trachomatis. Thus, in the current study, we modified the pGFP::SW2 plasmid
      by fusing a blasticidin S deaminase gene to the GFP gene to establish blasticidin
      resistance as a selectable marker and replacing the beta-lactamase gene with the
      Sh ble gene to eliminate the penicillin resistance. The new vector termed
      pGFPBSD/Z::SW2 was used for transforming plasmid-free C. trachomatis serovar D
      organisms. Using blasticidin for selection, stable transformants were obtained.
      The GFP-BSD fusion protein was detected in cultures infected with the
      pGFPBSD/Z::SW2-trasnformed serovar D organisms. The transformation restored the
      plasmid property to the plasmid-free serovar D organisms. Thus, we have
      successfully modified the pGFP::SW2 transformation system for studying the
      biology and pathogenesis of other STI-causing serovars of C. trachomatis. 

PMID- 24303024
TI  - Disturbance frequency determines morphology and community development in multi
      species biofilm at the landscape scale.
AB  - Many natural and engineered biofilm systems periodically face disturbances. Here
      we present how the recovery time of a biofilm between disturbances (expressed as
      disturbance frequency) shapes the development of morphology and community
      structure in a multi-species biofilm at the landscape scale. It was hypothesized
      that a high disturbance frequency favors the development of a stable adapted
      biofilm system while a low disturbance frequency promotes a dynamic biofilm
      response. Biofilms were grown in laboratory-scale reactors over a period of 55-70
      days and exposed to the biocide monochloramine at two frequencies: daily or
      weekly pulse injections. One untreated reactor served as control. Biofilm
      morphology and community structure were followed on comparably large biofilm
      areas at the landscape scale using automated image analysis (spatial gray level
      dependence matrices) and community fingerprinting (single-strand conformation
      polymorphisms). We demonstrated that a weekly disturbed biofilm developed a
      resilient morphology and community structure. Immediately after the disturbance,
      the biofilm simplified but recovered its initial complex morphology and community
      structure between two biocide pulses. In the daily treated reactor, one organism
      largely dominated a morphologically simple and stable biofilm. Disturbances
      primarily affected the abundance distribution of already present bacterial taxa
      but did not promote growth of previously undetected organisms. Our work indicates
      that disturbances can be used as lever to engineer biofilms by maintaining a
      biofilm between two developmental states. 

PMID- 24303025
TI  - Novel factors in the pathogenesis of psoriasis and potential drug candidates are
      found with systems biology approach.
AB  - Psoriasis is a multifactorial inflammatory skin disease characterized by
      increased proliferation of keratinocytes, activation of immune cells and
      susceptibility to metabolic syndrome. Systems biology approach makes it possible
      to reveal novel important factors in the pathogenesis of the disease. Protein
      protein, protein-DNA, merged (containing both protein-protein and protein-DNA
      interactions) and chemical-protein interaction networks were constructed
      consisting of differentially expressed genes (DEG) between lesional and non
      lesional skin samples of psoriatic patients and/or the encoded proteins. DEGs
      were determined by microarray meta-analysis using MetaOMICS package. We used
      STRING for protein-protein, CisRED for protein-DNA and STITCH for chemical
      protein interaction network construction. General network-, cluster- and motif
      analysis were carried out in each network. Many DEG-coded proteins (CCNA2, FYN,
      PIK3R1, CTGF, F3) and transcription factors (AR, TFDP1, MEF2A, MECOM) were
      identified as central nodes, suggesting their potential role in psoriasis
      pathogenesis. CCNA2, TFDP1 and MECOM might play role in the hyperproliferation of
      keratinocytes, whereas FYN may be involved in the disturbed immunity in
      psoriasis. AR can be an important link between inflammation and insulin
      resistance, while MEF2A has role in insulin signaling. A controller sub-network
      was constructed from interlinked positive feedback loops that with the capability
      to maintain psoriatic lesional phenotype. Analysis of chemical-protein
      interaction networks detected 34 drugs with previously confirmed disease
      modifying effects, 23 drugs with some experimental evidences, and 21 drugs with
      case reports suggesting their positive or negative effects. In addition, 99
      unpublished drug candidates were also found, that might serve future treatments
      for psoriasis. 

PMID- 24303026
TI  - Dyskerin localizes to the mitotic apparatus and is required for orderly mitosis
      in human cells.
AB  - Dyskerin is a highly conserved, nucleolar RNA-binding protein with established
      roles in small nuclear ribonucleoprotein biogenesis, telomerase and telomere
      maintenance and precursor rRNA processing. Telomerase is functional during S
      phase and the bulk of rRNA maturation occurs during G1 and S phases; both
      processes are inactivated during mitosis. Yet, we show that during the course of
      cell cycle progression, human dyskerin expression peaks during G2/M in parallel
      with the upregulation of pro-mitotic factors. Dyskerin redistributed from the
      nucleolus in interphase cells to the perichromosomal region during prometaphase,
      metaphase and anaphase. With continued anaphase progression, dyskerin also
      localized to the cytoplasm within the mid-pole region. Loss of dyskerin function
      via siRNA-mediated depletion promoted G2/M accumulation and this was accompanied
      by an increased mitotic index and activation of the spindle assembly checkpoint.
      Live cell imaging further revealed an array of mitotic defects including delayed
      prometaphase progression, a significantly increased incidence of multi-polar
      spindles, and anaphase bridges culminating in micronucleus formation. Together,
      these findings suggest that dyskerin is a highly dynamic protein throughout the
      cell cycle and increases the repertoire of fundamental cellular processes that
      are disrupted by absence of its normal function. 

PMID- 24303027
TI  - Potential early predictors for outcomes of experimental hemorrhagic shock induced
      by uncontrolled internal bleeding in rats.
AB  - Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the
      leading cause of death in civilian and military environments. Hemorrhagic deaths
      usually occur within the first 6 hours of admission to hospital; therefore, early
      prehospital identification of patients who are at risk for developing shock may
      improve survival. The aims of the current study were: 1. To establish and
      characterize a unique model of uncontrolled internal hemorrhage induced by
      massive renal injury (MRI), of different degrees (20-35% unilateral nephrectomy)
      in rats, 2. To identify early biomarkers those best predict the outcome of severe
      internal hemorrhage. For this purpose, male Sprague Dawley rats were anesthetized
      and cannulas were inserted into the trachea and carotid artery. After abdominal
      laparotomy, the lower pole of the kidney was excised. During 120 minutes,
      hematocrit, pO2, pCO2, base excess, potassium, lactate and glucose were measured
      from blood samples, and mean arterial pressure (MAP) was measured through
      arterial tracing. After 120 minutes, blood loss was determined. Statistical
      prediction models of mortality and amount of blood loss were performed. In this
      model, the lowest blood loss and mortality rate were observed in the group with
      20% nephrectomy. Escalation of the extent of nephrectomy to 25% and 30%
      significantly increased blood loss and mortality rate. Two phases of hemodynamic
      and biochemical response to MRI were noticed: the primary phase, occurring during
      the first 15 minutes after injury, and the secondary phase, beginning 30 minutes
      after the induction of bleeding. A Significant correlation between early blood
      loss and mean arterial pressure (MAP) decrements and survival were noted. Our
      data also indicate that prediction of outcome was attainable in the very early
      stages of blood loss, over the first 15 minutes after the injury, and that blood
      loss and MAP were the strongest predictors of mortality. 

PMID- 24303028
TI  - In-situ optical and acoustical measurements of the buoyant cyanobacterium p.
      Rubescens: spatial and temporal distribution patterns.
AB  - Optical (fluorescence) and acoustic in-situ techniques were tested in their
      ability to measure the spatial and temporal distribution of plankton in
      freshwater ecosystems with special emphasis on the harmful and buoyant
      cyanobacterium P. rubescens. Fluorescence was measured with the multi-spectral
      FluoroProbe (Moldaenke FluoroProbe, MFP) and a Seapoint Chlorophyll Fluorometer
      (SCF). In-situ measurements of the acoustic backscatter strength (ABS) were
      conducted with three different acoustic devices covering multiple acoustic
      frequencies (614 kHz ADCP, 2 MHz ADP, and 6 MHz ADV). The MFP provides a fast and
      reliable technique to measure fluorescence at different wavelengths in situ,
      which allows discriminating between P. rubescens and other phytoplankton species.
      All three acoustic devices are sensitive to P. rubescens even if other
      scatterers, e.g., zooplankton or suspended sediment, are present in the water
      column, because P. rubescens containing gas vesicles has a strong density
      difference and hence acoustic contrast to the ambient water and other scatterers.
      After calibration, the combination of optical and acoustical measurements not
      only allows qualitative and quantitative observation of P. rubescens, but also
      distinction between P. rubescens, other phytoplankton, and zooplankton. As the
      measuring devices can sample in situ at high rates they enable assessment of
      plankton distributions at high temporal (minutes) and spatial (decimeters)
      resolution or covering large temporal (seasonal) and spatial (basin scale)
      scales. 

PMID- 24303029
TI  - Paratuberculosis vaccination causes only limited cross-reactivity in the skin
      test for diagnosis of bovine tuberculosis.
AB  - Although there is a wide consensus on the efficacy of paratuberculosis
      vaccination to limit economic losses, its use has been restricted because of its
      interference in the diagnosis of tuberculosis. Data from a vaccine clinical trial
      in the Basque Country (Spain) has been evaluated in relationship with bovine
      tuberculosis intradermal test results. The trial included two herds applying a
      Test and Culling strategy and five applying an inactivated vaccine. The vaccine
      was applied to animals of all ages present in each vaccinated herd when joining
      the trial, and then to all the replacers within their first three months of life.
      Yearly testing done with the comparative intradermal test (CIT) was applied to
      all animals older than 6 weeks. Between 2005 and 2011, the study generated 2,033
      records from Vaccinated Herds (VH) and 2,252 from Test and Cull herds (TC). Pre
      vaccination positive results rate was 2.40% among the 7 herds in the single
      bovine intradermal tuberculin test (BSIT). Two years later it rose to 20.42% in
      the VH and remained below at 0.75% in the TC. Applying the CIT reduced these
      rates to only 0.58% in the VH and to 0.25% in the TC ons. Regarding time since
      each animal joined the program, the proportion of positives to BSIT was variable
      and, in some cases, significantly different between time points. With regard to
      the age of vaccination, no significant differences were found between vaccination
      within the first year of life and afterwards. Vaccinated animals showed seventeen
      times more reactions than the non-vaccinated in the BSIT, but only four times
      more in the CIT. In conclusion, comparative intradermal test can be a useful tool
      to differentiate paratuberculosis vaccine cross-reactions from specific bovine
      tuberculosis reactions according to the European and Spanish legislation. 

PMID- 24303030
TI  - Invasion pathway of the Ctenophore Mnemiopsis leidyi in the Mediterranean Sea.
AB  - Gelatinous zooplankton outbreaks have increased globally owing to a number of
      human-mediated factors, including food web alterations and species introductions.
      The invasive ctenophore Mnemiopsis leidyi entered the Black Sea in the early
      1980s. The invasion was followed by the Azov, Caspian, Baltic and North Seas,
      and, most recently, the Mediterranean Sea. Previous studies identified two
      distinct invasion pathways of M. leidyi from its native range in the western
      Atlantic Ocean to Eurasia. However, the source of newly established populations
      in the Mediterranean Sea remains unclear. Here we build upon our previous study
      and investigate sequence variation in both mitochondrial (Cytochrome c Oxidase
      subunit I) and nuclear (Internal Transcribed Spacer) markers in M. leidyi,
      encompassing five native and 11 introduced populations, including four from the
      Mediterranean Sea. Extant genetic diversity in Mediterranean populations (n = 8,
      N a = 10) preclude the occurrence of a severe genetic bottleneck or founder
      effects in the initial colonizing population. Our mitochondrial and nuclear
      marker surveys revealed two possible pathways of introduction into Mediterranean
      Sea. In total, 17 haplotypes and 18 alleles were recovered from all surveyed
      populations. Haplotype and allelic diversity of Mediterranean populations were
      comparable to populations from which they were likely drawn. The distribution of
      genetic diversity and pattern of genetic differentiation suggest initial
      colonization of the Mediterranean from the Black-Azov Seas (pairwise F ST = 0.001
      0.028). However, some haplotypes and alleles from the Mediterranean Sea were not
      detected from the well-sampled Black Sea, although they were found in Gulf of
      Mexico populations that were also genetically similar to those in the
      Mediterranean Sea (pairwise F ST = 0.010-0.032), raising the possibility of
      multiple invasion sources. Multiple introductions from a combination of Black Sea
      and native region sources could be facilitated by intense local and
      transcontinental shipping activity, respectively. 

PMID- 24303031
TI  - The Campylobacter jejuni Cj0268c protein is required for adhesion and invasion in
      vitro.
AB  - Adherence of Campylobacter jejuni to its particular host cells is mediated by
      several pathogen proteins. We screened a transposon-based mutant library of C.
      jejuni in order to identify clones with an invasion deficient phenotype towards
      Caco2 cells and detected a mutant with the transposon insertion in gene cj0268c.
      In vitro characterization of a generated non-random mutant, the mutant
      complemented with an intact copy of cj0268c and parental strain NCTC 11168
      confirmed the relevance of Cj0268c in the invasion process, in particular
      regarding adherence to host cells. Whereas Cj0268c does not impact
      autoagglutination or motility of C. jejuni, heterologous expression in E. coli
      strain DH5alpha enhanced the potential of the complemented E. coli strain to
      adhere to Caco2 cells significantly and, thus, indicates that Cj0268c does not
      need to interact with other C. jejuni proteins to develop its adherence-mediating
      phenotype. Flow cytometric measurements of E. coli expressing Cj0268c indicate a
      localization of the protein in the periplasmic space with no access of its C
      terminus to the bacterial surface. Since a respective knockout mutant possesses
      clearly reduced resistance to Triton X-100 treatment, Cj0268c contributes to the
      stability of the bacterial cell wall. Finally, we could show that the presence of
      cj0268c seems to be ubiquitous in isolates of C. jejuni and does not correlate
      with specific clonal groups regarding pathogenicity or pathogen metabolism. 

PMID- 24303032
TI  - Prioritization of cancer marker candidates based on the immunohistochemistry
      staining images deposited in the human protein atlas.
AB  - Cancer marker discovery is an emerging topic in high-throughput quantitative
      proteomics. However, the omics technology usually generates a long list of marker
      candidates that requires a labor-intensive filtering process in order to screen
      for potentially useful markers. Specifically, various parameters, such as the
      level of overexpression of the marker in the cancer type of interest, which is
      related to sensitivity, and the specificity of the marker among cancer groups,
      are the most critical considerations. Protein expression profiling on the basis
      of immunohistochemistry (IHC) staining images is a technique commonly used during
      such filtering procedures. To systematically investigate the protein expression
      in different cancer versus normal tissues and cell types, the Human Protein Atlas
      is a most comprehensive resource because it includes millions of high-resolution
      IHC images with expert-curated annotations. To facilitate the filtering of
      potential biomarker candidates from large-scale omics datasets, in this study we
      have proposed a scoring approach for quantifying IHC annotation of paired
      cancerous/normal tissues and cancerous/normal cell types. We have comprehensively
      calculated the scores of all the 17219 tested antibodies deposited in the Human
      Protein Atlas based on their accumulated IHC images and obtained 457110 scores
      covering 20 different types of cancers. Statistical tests demonstrate the ability
      of the proposed scoring approach to prioritize cancer-specific proteins. Top 100
      potential marker candidates were prioritized for the 20 cancer types with
      statistical significance. In addition, a model study was carried out of 1482
      membrane proteins identified from a quantitative comparison of paired cancerous
      and adjacent normal tissues from patients with colorectal cancer (CRC). The
      proposed scoring approach demonstrated successful prioritization and identified
      four CRC markers, including two of the most widely used, namely CEACAM5 and
      CEACAM6. These results demonstrate the potential of this scoring approach in
      terms of cancer marker discovery and development. All the calculated scores are
      available at http://bal.ym.edu.tw/hpa/. 

PMID- 24303033
TI  - Errors and their mitigation at the kirchhoff-law-johnson-noise secure key
      exchange.
AB  - A method to quantify the error probability at the Kirchhoff-law-Johnson-noise
      (KLJN) secure key exchange is introduced. The types of errors due to statistical
      inaccuracies in noise voltage measurements are classified and the error
      probability is calculated. The most interesting finding is that the error
      probability decays exponentially with the duration of the time window of single
      bit exchange. The results indicate that it is feasible to have so small error
      probabilities of the exchanged bits that error correction algorithms are not
      required. The results are demonstrated with practical considerations. 

PMID- 24303034
TI  - Immunization using GroEL decreases Clostridium difficile intestinal colonization.
AB  - Clostridium difficile is a pathogen which is responsible for diarrhea and
      colitis, particularly after treatment with antibiotics. Clinical signs are mainly
      due to two toxins, TcdA and TcdB. However, the first step of pathogenesis is the
      colonization process. We evaluated C. difficile surface proteins as vaccine
      antigens in the hamster model to prevent intestinal colonization. This
      vaccination induced a partial protection of hamsters against death after a C.
      difficile challenge. A proteomic analysis of animal sera allowed us to identify
      proteins which could be responsible for the protection observed. Among these
      proteins, we identified the GroEL heat shock protein. To confirm the role of the
      specific GroEL antibodies in the delayed C. difficile colonization of hamsters,
      we performed an immunization assay in a mouse model. After intranasal
      immunization with the recombinant protein GroEL, we observed a lower C. difficile
      intestinal colonization in the immunized group as compared to the control group. 

PMID- 24303035
TI  - Does iterative reconstruction lower CT radiation dose: evaluation of 15,000
      examinations.
AB  - PURPOSE: Evaluation of 15,000 computed tomography (CT) examinations to
      investigate if iterative reconstruction (IR) reduces sustainably radiation
      exposure. METHOD AND MATERIALS: Information from 15,000 CT examinations was
      collected, including all aspects of the exams such as scan parameter, patient
      information, and reconstruction instructions. The examinations were acquired
      between January 2010 and December 2012, while after 15 months a first generation
      IR algorithm was installed. To collect the necessary information from PACS, RIS,
      MPPS and structured reports a Dose Monitoring System was developed. To harvest
      all possible information an optical character recognition system was integrated,
      for example to collect information from the screenshot CT-dose report. The tool
      transfers all data to a database for further processing such as the calculation
      of effective dose and organ doses. To evaluate if IR provides a sustainable dose
      reduction, the effective dose values were statistically analyzed with respect to
      protocol type, diagnostic indication, and patient population. RESULTS: IR has the
      potential to reduce radiation dose significantly. Before clinical introduction of
      IR the average effective dose was 10.1+/-7.8mSv and with IR 8.9+/-7.1mSv
      (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols,
      such as in aortic CTAs (before IR: average14.2+/-7.8mSv; median11.4mSv /with
      IR:average9.9+/-7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7+/
      6.2mSV; median7.7mSv /with IR: average6.4+/-4.7mSv; median4.8mSv) the dose
      reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose
      scans of the cranial (for example sinuses) the reduction is not significant
      (before IR:average6.6+/-5.8mSv; median3.9mSv/with IR:average6.0+/-3.1mSV;
      median3.2mSv). CONCLUSION: The dose aspect remains a priority in CT research.
      Iterative reconstruction algorithms reduce sustainably and significantly
      radiation dose in the clinical routine. Our results illustrate that not only in
      studies with a limited number of patients but also in the clinical routine, IRs
      provide long-term dose saving.

PMID- 24303036
TI  - Niaspan attenuates the adverse effects of bone marrow stromal cell treatment of
      stroke in type one diabetic rats.
AB  - AIMS: Our previous studies have found that bone-marrow-stromal cells (BMSC)
      therapy improves functional recovery after stroke in non-diabetic rats while
      increases brain hemorrhage and induces arteriosclerosis-like changes in type-one
      diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular
      stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage
      in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC
      with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.
      METHODS: T1DM-rats induced by streptozotocin were subjected to 2 hours of middle
      cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5*10(6)); 3)
      Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5*10(6)) +Niaspan (40 mg/kg, daily
      for 14 days) combination starting at 24 hours after MCAo. All rats were monitored
      for 14 days. RESULTS: Combination BMSC+Niaspan treatment of T1DM-MCAo rats did
      not increase brain hemorrhage, and significantly decreased BBB leakage and
      vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix
      metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal
      carotid-artery compared to non-treatment control and BMSC monotherapy animals.
      CONCLUSIONS: Combination therapy using BMSC with Niaspan decreases BBB leakage
      and cerebral arteriosclerosis-like changes. These beneficial effects may be
      attributed to the decreased expression of Angiogenin, MMP9 and ED1.

PMID- 24303037
TI  - Biodiversity promotes tree growth during succession in subtropical forest.
AB  - Losses of plant species diversity can affect ecosystem functioning, with
      decreased primary productivity being the most frequently reported effect in
      experimental plant assemblages, including tree plantations. Less is known about
      the role of biodiversity in natural ecosystems, including forests, despite their
      importance for global biogeochemical cycling and climate. In general,
      experimental manipulations of tree diversity will take decades to yield final
      results. To date, biodiversity effects in natural forests therefore have only
      been reported from sample surveys or meta-analyses with plots not initially
      selected for diversity. We studied biomass and growth of subtropical forests
      stands in southeastern China. Taking advantage of variation in species
      recruitment during secondary succession, we adopted a comparative study design
      selecting forest plots to span a gradient in species richness. We repeatedly
      censored the stem diameter of two tree size cohorts, comprising 93 species
      belonging to 57 genera and 33 families. Tree size and growth were analyzed in
      dependence of species richness, the functional diversity of growth-related
      traits, and phylogenetic diversity, using both general linear and structural
      equation modeling. Successional age covaried with diversity, but differently so
      in the two size cohorts. Plot-level stem basal area and growth were positively
      related with species richness, while growth was negatively related to
      successional age. The productivity increase in species-rich, functionally and
      phylogenetically diverse plots was driven by both larger mean sizes and larger
      numbers of trees. The biodiversity effects we report exceed those from
      experimental studies, sample surveys and meta-analyses, suggesting that
      subtropical tree diversity is an important driver of forest productivity and re
      growth after disturbance that supports the provision of ecological services by
      these ecosystems. 

PMID- 24303038
TI  - Mice with deficient BK channel function show impaired prepulse inhibition and
      spatial learning, but normal working and spatial reference memory.
AB  - Genetic variations in the large-conductance, voltage- and calcium activated
      potassium channels (BK channels) have been recently implicated in mental
      retardation, autism and schizophrenia which all come along with severe cognitive
      impairments. In the present study we investigate the effects of functional BK
      channel deletion on cognition using a genetic mouse model with a knock-out of the
      gene for the pore forming alpha-subunit of the channel. We tested the F1
      generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted
      in both parent strains. We first evaluated hearing and motor function to
      establish the suitability of this model for cognitive testing. Auditory brain
      stem responses to click stimuli showed no threshold differences between knockout
      mice and their wild-type littermates. Despite of muscular tremor, reduced grip
      force, and impaired gait, knockout mice exhibited normal locomotion. These
      findings allowed for testing of sensorimotor gating using the acoustic startle
      reflex, as well as of working memory, spatial learning and memory in the Y-maze
      and the Morris water maze, respectively. Prepulse inhibition on the first day of
      testing was normal, but the knockout mice did not improve over the days of
      testing as their wild-type littermates did. Spontaneous alternation in the y-maze
      was normal as well, suggesting that the BK channel knock-out does not impair
      working memory. In the Morris water maze knock-out mice showed significantly
      slower acquisition of the task, but normal memory once the task was learned.
      Thus, we propose a crucial role of the BK channels in learning, but not in memory
      storage or recollection. 

PMID- 24303039
TI  - Chromosomal bands affected by acute oil exposure and DNA repair errors.
AB  - BACKGROUND: In a previous study, we showed that individuals who had participated
      in oil clean-up tasks after the wreckage of the Prestige presented an increase of
      structural chromosomal alterations two years after the acute exposure had
      occurred. Other studies have also reported the presence of DNA damage during
      acute oil exposure, but little is known about the long term persistence of
      chromosomal alterations, which can be considered as a marker of cancer risk.
      OBJECTIVES: We analyzed whether the breakpoints involved in chromosomal damage
      can help to assess the risk of cancer as well as to investigate their possible
      association with DNA repair efficiency. METHODS: Cytogenetic analyses were
      carried out on the same individuals of our previous study and DNA repair errors
      were assessed in cultures with aphidicolin. RESULTS: Three chromosomal bands,
      2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in
      DNA repair mechanisms, expressed as chromosomal damage, was significantly higher
      in exposed-oil participants than in those not exposed (p= 0.016). CONCLUSION: The
      present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which
      are commonly involved in hematological cancer, could be considered useful
      genotoxic oil biomarkers. Moreover, breakages in these bands could induce
      chromosomal instability, which can explain the increased risk of cancer (leukemia
      and lymphomas) reported in chronically benzene-exposed individuals. In addition,
      it has been determined that the individuals who participated in clean-up of the
      oil spill presented an alteration of their DNA repair mechanisms two years after
      exposure.

PMID- 24303040
TI  - Effect of Calstabin1 depletion on calcium transients and energy utilization in
      muscle fibers and treatment opportunities with RyR1 stabilizers.
AB  - Depletion of calstabin1 (FKBP12) from the RyR1 channel and consequential calcium
      leakage from the sarcoplasmic reticulum (SR) is found in certain disease
      conditions such as dystrophy, aging or muscle overuse. Here, we first assessed
      the effect of calstabin1 depletion on resting Ca(2+) levels and transients. We
      found that depletion of calstabin1 with the calstabin1-dissociation compound
      FK506 increased the release of calcium from the SR by 14 % during tetanic
      stimulation (50 Hz, 300 ms) and delayed cytosolic calcium removal. However, we
      did not find a significant increase in resting cytosolic Ca(2+) levels.
      Therefore, we tested if increased SERCA activity could counterbalance calcium
      leakage. By measuring the energy utilization of muscle fibers with and without
      FK506 treatment, we observed that FK506-treatment increased oxygen consumption by
      125% compared to baseline levels. Finally, we found that pretreatment of muscle
      fibers with the RyR1 stabilizer JTV-519 led to an almost complete normalization
      of calcium flux dynamics and energy utilization. We conclude that cytosolic
      calcium levels are mostly preserved in conditions with leaky RyR1 channels due to
      increased SERCA activity. Therefore, we suggest that RyR1 leakiness might lead to
      chronic metabolic stress, followed by cellular damage, and RyR1 stabilizers could
      potentially protect diseased muscle tissue. 

PMID- 24303042
TI  - Higher carbohydrate antigen 125 levels are associated with increased risk of
      coronary heart disease in elderly chinese: a population-based case-control study.
AB  - BACKGROUND: High carbohydrate antigen 125 (CA-125) level was reported to be
      associated with some cardiac dysfunctions, such as chronic heart failure, but the
      relationship between CA-125 level and coronary heart disease (CHD) risk remains
      unclear. The aim of this study was to explore the potential association in a
      Chinese older population. METHODS: In a population-based case-control study
      conducted in a Chinese older population, serum CA-125 levels were measured in
      1177 diagnosed CHD patients and 3531 age and sex matched control subjects without
      CHD. RESULTS: Serum CA-125 level was significantly higher in CHD patients than
      controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI,
      physical activity, hypertension, dyslipidemia, diabetes mellitus, medication
      history and family history of CHD and myocardial infarction. CHD risk was doubled
      (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to
      those in the lowest quartile of CA-125 level (P trend < 0.001). Furthermore, CA
      125 levels were associated with CHD risks in subjects with age over 60 years (OR:
      2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current
      drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04,
      95%CI: 1.71-2.43). CONCLUSIONS: Elevated serum CA-125 level might be associated
      with increased risk of coronary heart disease in the Chinese older population.
      Further investigations are needed to identify the possible biological role of CA
      125 in CHD development in the future.

PMID- 24303041
TI  - Identification of a novel zinc metalloprotease through a global analysis of
      Clostridium difficile extracellular proteins.
AB  - Clostridium difficile is a major cause of infectious diarrhea worldwide. Although
      the cell surface proteins are recognized to be important in clostridial
      pathogenesis, biological functions of only a few are known. Also, apart from the
      toxins, proteins exported by C. difficile into the extracellular milieu have been
      poorly studied. In order to identify novel extracellular factors of C. difficile,
      we analyzed bacterial culture supernatants prepared from clinical isolates, 630
      and R20291, using liquid chromatography-tandem mass spectrometry. The majority of
      the proteins identified were non-canonical extracellular proteins. These could be
      largely classified into proteins associated to the cell wall (including CWPs and
      extracellular hydrolases), transporters and flagellar proteins. Seven unknown
      hypothetical proteins were also identified. One of these proteins, CD630_28300,
      shared sequence similarity with the anthrax lethal factor, a known zinc
      metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is
      able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner.
      Using site-directed mutagenesis, we identified residues important in zinc binding
      and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the
      fibronectin network produced by human fibroblasts. Thus, by analyzing the
      exoproteome of C. difficile, we identified a novel extracellular metalloprotease
      that may be important in key steps of clostridial pathogenesis. 

PMID- 24303043
TI  - Microbiota dynamics in patients treated with fecal microbiota transplantation for
      recurrent Clostridium difficile infection.
AB  - Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous
      colitis and is responsible for a large and increasing fraction of hospital
      acquired infections. Fecal microbiota transplantation (FMT) is an alternate
      treatment option for recurrent C. difficile infection (RCDI) refractory to
      antibiotic therapy. It has recently been discussed favorably in the clinical and
      scientific communities and is receiving increasing public attention. However,
      short- and long-term health consequences of FMT remain a concern, as the effects
      of the transplanted microbiota on the patient remain unknown. To shed light on
      microbial events associated with RCDI and treatment by FMT, we performed fecal
      microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of
      healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient
      and healthy donor samples collected up to one year after FMT were studied
      longitudinally, including one post-FMT patient with antibiotic-associated relapse
      three months after FMT. This analysis allowed us not only to confirm prior
      reports that RCDI is associated with reduced diversity and compositional changes
      in the fecal microbiota, but also to characterize previously undocumented post
      FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or
      Enterobacteriaceae were significantly increased and putative butyrate producers,
      such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples
      from RCDI patients before FMT as compared to post-FMT patient and healthy donor
      samples. RCDI patient samples showed more case-specific variations than post-FMT
      patient and healthy donor samples. However, none of the bacterial groups were
      invariably associated with RCDI or successful treatment by FMT. Overall
      microbiota compositions in post-FMT patients, specifically abundances of the
      above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT,
      suggesting that full microbiota recovery from RCDI may take much longer than
      expected based on the disappearance of diarrheal symptoms immediately after FMT. 

PMID- 24303044
TI  - Inhibition of elongation factor-2 kinase augments the antitumor activity of
      Temozolomide against glioma.
AB  - BACKGROUND: Glioblastoma multiforme (GBM), the most common form of brain cancer
      with an average survival of less than 12 months, is a highly aggressive and fatal
      disease characterized by survival of glioma cells following initial treatment,
      invasion through the brain parenchyma and destruction of normal brain tissues,
      and ultimately resistance to current treatments. Temozolomide (TMZ) is commonly
      used chemotherapy for treatment of primary and recurrent high-grade gliomas.
      Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this
      study, we sought to determine whether eEF-2 kinase affected the sensitivity of
      glioma cells to treatment with TMZ. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA
      interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro
      and in vivo glioma models, we observed that inhibition of eEF-2 kinase could
      enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was
      associated with blockade of autophagy and augmentation of apoptosis caused by
      TMZ. CONCLUSIONS/SIGNIFICANCE: These findings demonstrated that targeting eEF-2
      kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase
      may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma.

PMID- 24303045
TI  - Population and genetic study of Vibrio cholerae from the amazon environment
      confirms that the WASA-1 prophage is the main marker of the epidemic strain that
      circulated in the region.
AB  - Vibrio cholerae is a natural inhabitant of many aquatic environments in the
      world. Biotypes harboring similar virulence-related gene clusters are the
      causative agents of epidemic cholera, but the majority of strains are harmless to
      humans. Since 1971, environmental surveillance for potentially pathogenic V.
      cholerae has resulted in the isolation of many strains from the Brazilian Amazon
      aquatic ecosystem. Most of these strains are from the non-O1/non-O139 serogroups
      (NAGs), but toxigenic O1 strains were isolated during the Latin America cholera
      epidemic in the region (1991-1996). A collection of environmental V. cholerae
      strains from the Brazilian Amazon belonging to pre-epidemic (1977-1990), epidemic
      (1991-1996), and post-epidemic (1996-2007) periods in the region, was analyzed.
      The presence of genes related to virulence within the species and the genetic
      relationship among the strains were studied. These variables and the information
      available concerning the strains were used to build a Bayesian multivariate
      dependency model to distinguish the importance of each variable in determining
      the others. Some genes related to the epidemic strains were found in
      environmental NAGs during and after the epidemic. Significant diversity among the
      virulence-related gene content was observed among O1 strains isolated from the
      environment during the epidemic period, but not from clinical isolates, which
      were analyzed as controls. Despite this diversity, these strains exhibited
      similar PFGE profiles. PFGE profiles were significant while separating
      potentially epidemic clones from indigenous strains. No significant correlation
      with isolation source, place or period was observed. The presence of the WASA-1
      prophage significantly correlated with serogroups, PFGE profiles, and the
      presence of virulence-related genes. This study provides a broad characterization
      of the environmental V. cholerae population from the Amazon, and also highlights
      the importance of identifying precisely defined genetic markers such as the WASA
      1 prophage for the surveillance of cholera. 

PMID- 24303046
TI  - Action recognition depends on observer's level of action control and social
      personality traits.
AB  - Humans recognize both the movement (physical) goals and action (conceptual) goals
      of individuals with whom they are interacting. Here, we assessed whether
      spontaneous recognition of others' goals depends on whether the observers control
      their own behavior at the movement or action level. We also examined the
      relationship between individual differences in empathy and ASD-like traits, and
      the processing of other individual's movement and action goals that are known to
      be encoded in the "mirroring" and "mentalizing" brain networks. In order to
      address these questions, we used a computer-based card paradigm that made it
      possible to independently manipulate movement and action congruency of observed
      and executed actions. In separate blocks, participants were instructed to select
      either the right or left card (movement-control condition) or the higher or lower
      card (action-control condition), while we manipulated action- and movement
      congruency of both actors' goals. An action-congruency effect was present in all
      conditions and the size of this effect was significantly correlated with self
      reported empathy and ASD-like traits. In contrast, movement-congruency effects
      were only present in the movement-control block and were strongly dependent on
      action-congruency. These results illustrate that spontaneous recognition of
      others' behavior depends on the control scheme that is currently adopted by the
      observer. The findings suggest that deficits in action recognition are related to
      abnormal synthesis of perceived movements and prior conceptual knowledge that are
      associated with activations in the "mirroring" and "mentalizing" cortical
      networks. 

PMID- 24303047
TI  - Evaluation of a FRET-peptide substrate to predict virulence in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa produces a number of proteases that are associated with
      virulence and disease progression. A substrate able to detect P. aeruginosa
      specific proteolytic activity could help to rapidly alert clinicians to the
      virulence potential of individual P. aeruginosa strains. For this purpose we
      designed a set of P. aeruginosa-specific fluorogenic substrates, comprising
      fluorescence resonance energy transfer (FRET)-labeled peptides, and evaluated
      their applicability to P. aeruginosa virulence in a range of clinical isolates. A
      FRET-peptide comprising three glycines (3xGly) was found to be specific for the
      detection of P. aeruginosa proteases. Further screening of 97 P. aeruginosa
      clinical isolates showed a wide variation in 3xGly cleavage activity. The absence
      of 3xGly degradation by a lasI knock out strain indicated that 3xGly cleavage by
      P. aeruginosa could be quorum sensing (QS)-related, a hypothesis strengthened by
      the observation of a strong correlation between 3xGly cleavage, LasA
      staphylolytic activity and pyocyanin production. Additionally, isolates able to
      cleave 3xGly were more susceptible to the QS inhibiting antibiotic azithromycin
      (AZM). In conclusion, we designed and evaluated a 3xGly substrate possibly useful
      as a simple tool to predict virulence and AZM susceptibility. 

PMID- 24303048
TI  - The invasive wetland plant Alternanthera philoxeroides shows a higher tolerance
      to waterlogging than its native Congener Alternanthera sessilis.
AB  - Plant invasion is one of the major threats to natural ecosystems. Phenotypic
      plasticity is considered to be important for promoting plant invasiveness. High
      tolerance of stress can also increase survival of invasive plants in adverse
      habitats. Limited growth and conservation of carbohydrate are considered to
      increase tolerance of flooding in plants. However, few studies have examined
      whether invasive species shows a higher phenotypic plasticity in response to
      waterlogging or a higher tolerance of waterlogging (lower plasticity) than native
      species. We conducted a greenhouse experiment to compare the growth and
      morphological and physiological responses to waterlogging of the invasive,
      clonal, wetland species Alternanthera philoxeroides with those of its co
      occurring, native, congeneric, clonal species Alternanthera sessilis. Plants of
      A. philoxeroides and A. sessilis were subjected to three treatments (control, 0
      and 60 cm waterlogging). Both A. philoxeroides and A. sessilis survived all
      treatments. Overall growth was lower in A. philoxeroides than in A. sessilis, but
      waterlogging negatively affected the growth of A. philoxeroides less strongly
      than that of A. sessilis. Alternanthera philoxeroides thus showed less
      sensitivity of growth traits (lower plasticity) and higher waterlogging
      tolerance. Moreover, the photosynthetic capacity of A. philoxeroides was higher
      than that of A. sessilis during waterlogging. Alternanthera philoxeroides also
      had higher total non-structural and non-soluble carbohydrate concentrations than
      A. sessilis at the end of treatments. Our results suggest that higher tolerance
      to waterlogging and higher photosynthetic capacity may partly explain the
      invasion success of A. philoxeroides in wetlands. 

PMID- 24303049
TI  - Effect of a low-protein diet supplemented with ketoacids on skeletal muscle
      atrophy and autophagy in rats with type 2 diabetic nephropathy.
AB  - A low-protein diet supplemented with ketoacids maintains nutritional status in
      patients with diabetic nephropathy. The activation of autophagy has been shown in
      the skeletal muscle of diabetic and uremic rats. This study aimed to determine
      whether a low-protein diet supplemented with ketoacids improves muscle atrophy
      and decreases the increased autophagy observed in rats with type 2 diabetic
      nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly
      divided into groups that received either a normal protein diet (NPD group), a low
      protein diet (LPD group) or a low-protein diet supplemented with ketoacids
      (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as
      control animals and received a normal protein diet (control group). We found that
      protein restriction attenuated proteinuria and decreased blood urea nitrogen and
      serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group
      showed a delay in body weight loss, an attenuation in soleus muscle mass loss and
      a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and
      protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62
      and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD
      compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the
      expression of autophagy-related genes; however, these differences were not
      statistically significant. In addition, LPD+KA abolished the upregulation of
      autophagy-related gene expression. Furthermore, the activation of autophagy in
      the NPD and LPD groups was confirmed by the appearance of autophagosomes or
      autolysosomes using electron microscopy, when compared with the Control and
      LPD+KA groups. Our results showed that LPD+KA abolished the activation of
      autophagy in skeletal muscle and decreased muscle loss in rats with type 2
      diabetic nephropathy. 

PMID- 24303050
TI  - Synonymous codon usage in TTSuV2: analysis and comparison with TTSuV1.
AB  - Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2,
      have become widely distributed in pig-farming countries in recent years. In this
      study, we performed a comprehensive analysis of synonymous codon usage bias in 41
      available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of
      TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically
      conserved. Values for the effective number of codons (ENC) indicated that the
      overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant,
      the most frequently occurring codons had an A or C at the third codon position.
      Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were
      located in different quadrants of the first two major axes. A plot of the ENC
      revealed that compositional constraint was the major factor determining the codon
      usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2
      isolates based on relative synonymous codon usage (RSCU) values suggested that
      there was no association between geographic distribution and codon bias of TTSuV2
      sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the
      corresponding host sequence indicated that the codon usage pattern of TTSuV2 was
      similar to that of TTSuV1. However the similarity was low for each virus and its
      host. These conclusions provide important insight into the synonymous codon usage
      pattern of TTSuV2, as well as better understangding of the molecular evolution of
      TTSuV2 genomes. 

PMID- 24303051
TI  - Early deficits in glycolysis are specific to striatal neurons from a rat model of
      huntington disease.
AB  - In Huntington disease (HD), there is increasing evidence for a link between
      mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and
      neurodegeneration but the precise nature, causes and order of these events remain
      to be determined. In this work, our objective was to evaluate mitochondrial
      respiratory function in intact, non-permeabilized, neurons derived from a
      transgenic rat model for HD compared to their wild type littermates by measuring
      oxygen consumption rates and extracellular acidification rates. Although HD
      striatal neurons had similar respiratory capacity as those from their wild-type
      littermates when they were incubated in rich medium containing a supra
      physiological glucose concentration (25 mM), pyruvate and amino acids,
      respiratory defects emerged when cells were incubated in media containing only a
      physiological cerebral level of glucose (2.5 mM). According to the concept that
      glucose is not the sole substrate used by the brain for neuronal energy
      production, we provide evidence that primary neurons can use lactate as well as
      pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we
      found no major deficits in HD striatal neurons' capacity to use pyruvate as a
      respiratory substrate compared to wild type littermates. Additionally, we used
      extracellular acidification rates to confirm a reduction in anaerobic glycolysis
      in the same cells. Interestingly, the metabolic disturbances observed in striatal
      neurons were not seen in primary cortical neurons, a brain region affected in
      later stages of HD. In conclusion, our results argue for a dysfunction in
      glycolysis, which might precede any defects in the respiratory chain itself, and
      these are early events in the onset of disease. 

PMID- 24303052
TI  - Leishmania braziliensis-reactive T cells are down-regulated in long-term cured
      cutaneous Leishmaniasis, but the renewal capacity of T effector memory
      compartments is preserved.
AB  - Leishmania (Viannia) braziliensis control and tissue damage relate to the
      effector immune response, which in turn affects clinical outcome. Leishmania
      reactive CD4(+) and CD8(+) T cells are expanded in long-term healed cutaneous
      leishmaniasis (hCL) patients but their functional characteristics remain to be
      determined. This study investigates antigen-specific recall in long-term healed
      CL caused by L. braziliensis infection. Healed CL subjects were grouped according
      to the time elapsed since the end of therapy: less than two years and two to five
      years. Activation phenotype (CD69(+) or CD25(+)) and subpopulations of memory T
      cell phenotypes [central memory (Tcm): CD45RO(+) CCR7(+) or effector memory
      (Tem): CD45RO(+) CCR7(-)] were quantified in ex vivo blood mononuclear cells and
      after Leishmania antigens stimuli. A reduction in the percentage of activated
      Leishmania-responder CD4(+) and CD8(+) T cells in hCL was associated with the
      time elapsed since clinical cure. Percentage of CD69(+) in TCD4(+) and TCD8(+)
      cells were negatively correlated with IL-10 levels. Ex vivo analyses showed
      contracted Tem CD4(+) and Tem CD8(+) compartments from hCL with long time elapsed
      since clinical cure, although renewal of these compartments was observed
      following in vitro exposure to leishmanial stimuli. Our results show that healed
      L. braziliensis infected patients exhibit a recall response to Leishmania
      antigens with evident expansion of effector memory T cells. Regulated leishmanial
      specific response seems to emerge only about two years after initial contact with
      the parasite antigens. 

PMID- 24303053
TI  - Arsenic exposure affects plasma insulin-like growth factor 1 (IGF-1) in children
      in rural Bangladesh.
AB  - BACKGROUND: Exposure to inorganic arsenic (As) through drinking water during
      pregnancy is associated with lower birth size and child growth. The aim of the
      study was to assess the effects of As exposure on child growth parameters to
      evaluate causal associations. METHODOLOGY/FINDINGS: Children born in a
      longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years
      (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by
      concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites
      (U-As). Associations with plasma concentrations of insulin-like growth factor 1
      (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B
      ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by
      linear regression analysis, adjusted for socioeconomic factor, parity and child
      sex. Child U-As (per 10 ug/L) was significantly inversely associated with
      concurrent plasma IGF-1 (beta=-0.27; 95% confidence interval: -0.50, -0.0042) at
      4.5 years. The effect was more obvious in girls (beta=-0.29; -0.59, 0.021) than
      in boys, and particularly in girls with adequate height (beta=-0.491; -0.97, 
      0.02) or weight (beta=-0.47; 0.97, 0.01). Maternal U-As was inversely associated
      with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a
      tendency of positive association between U-As and plasma PO4 in stunted boys
      (beta=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA,
      arsenic metabolite) (median split at 9.7%), a much stronger inverse association
      between U-As and IGF-1 in the girls (beta=-0.41; -0.77, -0.03) was obtained above
      the median split. CONCLUSION: The results suggest that As-related growth
      impairment in children is mediated, at least partly, through suppressed IGF-1
      levels.

PMID- 24303054
TI  - Hevin plays a pivotal role in corneal wound healing.
AB  - BACKGROUND: Hevin is a matricellular protein involved in tissue repair and
      remodeling via interaction with the surrounding extracellular matrix (ECM)
      proteins. In this study, we examined the functional role of hevin using a corneal
      stromal wound healing model achieved by an excimer laser-induced irregular
      phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin(-/-)) mice. We also
      investigated the effects of exogenous supplementation of recombinant human hevin
      (rhHevin) to rescue the stromal cellular components damaged by the excimer laser.
      METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT) and hevin (-/-) mice were divided
      into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naive
      without any treatment. Group II received epithelial debridement and underwent
      IrrPTK using excimer laser. Group III received topical application of rhHevin
      after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix
      remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy,
      light microscopy (LM), transmission electron microscopy (TEM),
      immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of
      hevin in IrrPTK-injured WT mice. Hevin (-/-) mice developed corneal haze as early
      as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4
      weeks. They also exhibited accumulation of inflammatory cells, fibrotic
      components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and
      TEM showed activated keratocytes (myofibroblasts), inflammatory debris and
      vascular tissues in the stroma. Exogenous application of rhHevin for 3 days
      reinstated inflammatory index of the corneal stroma similar to WT mice.
      CONCLUSIONS/SIGNIFICANCE: Hevin is transiently expressed in the IrrPTK-injured
      corneas and loss of hevin predisposes them to aberrant wound healing. Hevin (-/-)
      mice develop early corneal haze characterized by severe chronic inflammation and
      stromal fibrosis that can be rescued with exogenous administration of rhHevin.
      Thus, hevin plays a pivotal role in the corneal wound healing.

PMID- 24303055
TI  - In vivo regulation of brain-derived neurotrophic factor in dorsal root ganglia is
      mediated by nerve growth factor-triggered Akt activation during cystitis.
AB  - The role of brain-derived neurotrophic factor (BDNF) in sensory hypersensitivity
      has been suggested; however the molecular mechanisms and signal transduction that
      regulate BDNF expression in primary afferent neurons during visceral inflammation
      are not clear. Here we used a rat model of cystitis and found that the mRNA and
      protein levels of BDNF were increased in the L6 dorsal root ganglia (DRG) in
      response to bladder inflammation. BDNF up-regulation in the L6 DRG was triggered
      by endogenous nerve growth factor (NGF) because neutralization of NGF with a
      specific NGF antibody reduced BDNF levels during cystitis. The neutralizing NGF
      antibody also subsequently reduced cystitis-induced up-regulation of the
      serine/threonine kinase Akt activity in L6 DRG. To examine whether the NGF
      induced Akt activation led to BDNF up-regulation in DRG in cystitis, we found
      that in cystitis the phospho-Akt immunoreactivity was co-localized with BDNF in
      L6 DRG, and prevention of the endogenous Akt activity in the L6 DRG by inhibition
      of phosphoinositide 3-kinase (PI3K) with a potent inhibitor LY294002 reversed
      cystitis-induced BDNF up-regulation. Further study showed that application of NGF
      to the nerve terminals of the ganglion-nerve two-compartmented preparation
      enhanced BDNF expression in the DRG neuronal soma; which was reduced by pre
      treatment of the ganglia with the PI3K inhibitor LY294002 and wortmannin. These
      in vivo and in vitro experiments indicated that NGF played an important role in
      the activation of Akt and subsequent up-regulation of BDNF in the sensory neurons
      in visceral inflammation such as cystitis. 

PMID- 24303056
TI  - Ultra-deep pyrosequencing of partial surface protein genes from infectious Salmon
      Anaemia virus (ISAV) suggest novel mechanisms involved in transition to
      virulence.
AB  - Uncultivable HPR0 strains of infectious salmon anaemia viruses (ISAVs) infecting
      gills are non-virulent putative precursors of virulent ISAVs (vISAVs) causing
      systemic disease in farmed Atlantic salmon (Salmo salar). The transition to
      virulence involves two molecular events, a deletion in the highly polymorphic
      region (HPR) of the hemagglutinin-esterase (HE) gene and a Q266->L266
      substitution or insertion next to the putative cleavage site (R267) in the fusion
      protein (F). We have performed ultra-deep pyrosequencing (UDPS) of these gene
      regions from healthy fish positive for HPR0 virus carrying full-length HPR
      sampled in a screening program, and a vISAV strain from an ISA outbreak at the
      same farming site three weeks later, and compared the mutant spectra. As the UDPS
      data shows the presence of both HE genotypes at both sampling times, and the
      outbreak strain was unlikely to be directly related to the HPR0 strain, this is
      the first report of a double infection with HPR0s and vISAVs. For F amplicon
      reads, mutation frequencies generating L266 codons in screening samples and Q266
      codons in outbreak samples were not higher than at any random site. We suggest
      quasispecies heterogeneity as well as RNA structural properties are linked to
      transition to virulence. More specifically, a mechanism where selected single
      point mutations in the full-length HPR alter the RNA structure facilitating
      single- or sequential deletions in this region is proposed. The data provides
      stronger support for the deletion hypothesis, as opposed to recombination, as the
      responsible mechanism for generating the sequence deletions in HE. 

PMID- 24303057
TI  - Transcriptional reprogramming of wheat and the hemibiotrophic pathogen Septoria
      tritici during two phases of the compatible interaction.
AB  - The disease septoria leaf blotch of wheat, caused by fungal pathogen Septoria
      tritici, is of worldwide concern. The fungus exhibits a hemibiotrophic lifestyle,
      with a long symptomless, biotrophic phase followed by a sudden transition to
      necrotrophy associated with host necrosis. Little is known about the systematic
      interaction between fungal pathogenicity and host responses at specific growth
      stages and the factors triggering the transition. In order to gain some insights
      into global transcriptome alterations in both host and pathogen during the two
      phases of the compatible interaction, disease transition was monitored using
      pathogenesis-related gene markers and H2O2 signature prior to RNA-Seq.
      Transcriptome analysis revealed that the slow symptomless growth was accompanied
      by minor metabolic responses and slightly suppressed defences in the host,
      whereas necrotrophic growth was associated with enhanced host responses involving
      energy metabolism, transport, signalling, defence and oxidative stress as well as
      a decrease in photosynthesis. The fungus expresses distinct classes of stage
      specific genes encoding potential effectors, probably first suppressing plant
      defence responses/facilitating the symptomless growth and later triggering life
      style transition and inducing host necrosis/facilitating the necrotrophic growth.
      Transport, signalling, anti-oxidative stress mechanisms and apoplastic nutrient
      acquisition play important roles in the entire infection process of S. tritici.
      Our findings uncover systematic S. tritici-induced expression profiles of wheat
      related to specific fungal infection strategies and provide a transcriptome
      resource for studying both hosts and pathogens in plant-Dothideomycete
      interactions. 

PMID- 24303058
TI  - Is torosaurus triceratops? Geometric morphometric evidence of late maastrichtian
      ceratopsid dinosaurs.
AB  - BACKGROUND: Recent assessments of morphological changes in the frill during
      ontogeny hypothesized that the late Maastrichtian horned dinosaur Torosaurus
      represents the "old adult" of Triceratops, although acceptance of this finding
      has been disputed on several lines of evidence. METHODOLOGY/PRINCIPAL FINDINGS:
      Examining the cranial morphology of 28 skulls in lateral view and 36 squamosals
      of Nedoceratops hatcheri, Triceratops spp. and Torosaurus spp. by means of
      landmark-based geometric morphometrics, we compared ontogenetic trajectories
      among these taxa. Principal Component Analysis and cluster analysis confirmed
      different cranial morphologies. Torosaurus shape space is well separated from
      Triceratops, whereas Triceratops horridus and Triceratops prorsus partially
      overlap within Triceratops shape space. Linear regressions between shape and size
      suggest different ontogenetic trajectories among these taxa. Results support the
      "traditional" taxonomic status of Torosaurus. We hypothesize that ontogeny drives
      cranial morphology with different patterns between Torosaurus and Triceratops.
      CONCLUSIONS/SIGNIFICANCE: Torosaurus is a distinct and valid taxon. Whether
      looking at entire skulls, skulls without the frill, frills alone, or squamosals,
      Torosaurus has different morphologies and distinct allometric trajectories
      compared to Triceratops. This new approach confirms the taxonomic status of
      Torosaurus as well as the comparatively low diversity of ceratopsids at the end
      of the Maastrichtian in North America.

PMID- 24303059
TI  - Floral transcriptome sequencing for SSR marker development and linkage map
      construction in the tea plant (Camellia sinensis).
AB  - Despite the worldwide consumption and high economic importance of tea, the plant
      (Camellia sinensis) is not well studied in molecular biology. Under the few
      circumstances in which the plant is studied, C. sinensis flowers, which are
      important for reproduction and cross-breeding, receive less emphasis than
      investigation of its leaves or roots. Using high-throughput Illumina RNA
      sequencing, we analyzed a C. sinensis floral transcriptome, and 26.9 million
      clean reads were assembled into 75,531 unigenes averaging 402 bp. Among them,
      50,792 (67.2%) unigenes were annotated with a BLAST search against the NCBI Non
      Redundant (NR) database and 10,290 (16.67%) were detected that contained one or
      more simple sequence repeats (SSRs). From these SSR-containing sequences, 2,439
      candidate SSR markers were developed and 720 were experimentally tested,
      validating 431 (59.9%) novel polymorphic SSR markers for C. sinensis. Then, a
      consensus SSR-based linkage map was constructed that covered 1,156.9 cM with 237
      SSR markers distributed in 15 linkage groups. Both transcriptome information and
      the genetic map of C. sinensis presented here offer a valuable foundation for
      molecular biology investigations such as functional gene isolation, quantitative
      trait loci mapping, and marker-assisted selection breeding in this important
      species. 

PMID- 24303060
TI  - Survey of innate immune responses to Burkholderia pseudomallei in human blood
      identifies a central role for lipopolysaccharide.
AB  - B. pseudomallei is a gram-negative bacterium that causes the tropical infection
      melioidosis. In northeast Thailand, mortality from melioidosis approaches 40%. As
      exemplified by the lipopolysaccharide-Toll-like receptor 4 interaction, innate
      immune responses to invading bacteria are precipitated by activation of host
      pathogen recognition receptors by pathogen associated molecular patterns. Human
      melioidosis is characterized by up-regulation of pathogen recognition receptors
      and pro-inflammatory cytokine release. In contrast to many gram-negative
      pathogens, however, the lipopolysaccharide of B. pseudomallei is considered only
      weakly inflammatory. We conducted a study in 300 healthy Thai subjects to
      investigate the ex vivo human blood response to various bacterial pathogen
      associated molecular patterns, including lipopolysaccharide from several
      bacteria, and to two heat-killed B. pseudomallei isolates. We measured cytokine
      levels after stimulation of fresh whole blood with a panel of stimuli. We found
      that age, sex, and white blood cell count modulate the innate immune response to
      B. pseudomallei. We further observed that, in comparison to other stimuli, the
      innate immune response to B. pseudomallei is most highly correlated with the
      response to lipopolysaccharide. The magnitude of cytokine responses induced by B.
      pseudomallei lipopolysaccharide was significantly greater than those induced by
      lipopolysaccharide from Escherichia coli and comparable to many responses induced
      by lipopolysaccharide from Salmonella minnesota despite lower amounts of lipid A
      in the B. pseudomallei lipopolysaccharide preparation. In human monocytes
      stimulated with B. pseudomallei, addition of polymyxin B or a TLR4/MD-2
      neutralizing antibody inhibited the majority of TNF-alpha production. Challenging
      existing views, our data indicate that the innate immune response to B.
      pseudomallei in human blood is largely driven by lipopolysaccharide, and that the
      response to B. pseudomallei lipopolysaccharide in blood is greater than the
      response to other lipopolysaccharide expressing isolates. Our findings suggest
      that B. pseudomallei lipopolysaccharide may play a central role in stimulating
      the host response in melioidosis. 

PMID- 24303061
TI  - Protocol to isolate a large amount of functional oligodendrocyte precursor cells
      from the cerebral cortex of adult mice and humans.
AB  - During development, oligodendrocytes are generated from oligodendrocyte precursor
      cells (OPCs), a cell type that is a significant proportion of the total cells (3
      8%) in the adult central nervous system (CNS) of both rodents and humans. Adult
      OPCs are responsible for the spontaneous remyelination that occurs in
      demyelinating diseases like Multiple Sclerosis (MS) and they constitute an
      interesting source of cells for regenerative therapy in such conditions. However,
      there is little data regarding the neurobiology of adult OPCs isolated from mice
      since an efficient method to isolate them has yet to be established. We have
      designed a protocol to obtain viable adult OPCs from the cerebral cortex of
      different mouse strains and we have compared its efficiency with other well-known
      methods. In addition, we show that this protocol is also useful to isolate
      functional OPCs from human brain biopsies. Using this method we can isolate
      primary cortical OPCs in sufficient quantities so as to be able to study their
      survival, maturation and function, and to facilitate an evaluation of their
      utility in myelin repair. 

PMID- 24303062
TI  - A systematic evaluation of integration free reprogramming methods for deriving
      clinically relevant patient specific induced pluripotent stem (iPS) cells.
AB  - A systematic evaluation of three different methods for generating induced
      pluripotent stem (iPS) cells was performed using the same set of parental cells
      in our quest to develop a feeder independent and xeno-free method for somatic
      cell reprogramming that could be transferred into a GMP environment. When using
      the BJ fibroblast cell line, the highest reprogramming efficiency (1.89% of
      starting cells) was observed with the mRNA based method which was almost 20 fold
      higher than that observed with the retrovirus (0.2%) and episomal plasmid (0.10%)
      methods. Standard characterisation tests did not reveal any differences in an
      array of pluripotency markers between the iPS lines derived using the various
      methods. However, when the same methods were used to reprogram three different
      primary fibroblasts lines, two derived from patients with rapid onset
      parkinsonism dystonia and one from an elderly healthy volunteer, we consistently
      observed higher reprogramming efficiencies with the episomal plasmid method,
      which was 4 fold higher when compared to the retroviral method and over 50 fold
      higher than the mRNA method. Additionally, with the plasmid reprogramming
      protocol, recombinant vitronectin and synthemax(r) could be used together with
      commercially available, fully defined, xeno-free essential 8 medium without
      significantly impacting the reprogramming efficiency. To demonstrate the
      robustness of this protocol, we reprogrammed a further 2 primary patient cell
      lines, one with retinosa pigmentosa and the other with Parkinsons disease. We
      believe that we have optimised a simple and reproducible method which could be
      used as a starting point for developing GMP protocols, a prerequisite for
      generating clinically relevant patient specific iPS cells. 

PMID- 24303063
TI  - Mammalian target of rapamycin complex I (mTORC1) activity in ras homologue
      enriched in brain (Rheb)-deficient mouse embryonic fibroblasts.
AB  - The Ras-like GTPase Rheb has been identified as a crucial activator of mTORC1.
      Activation most likely requires a direct interaction between Rheb and mTOR, but
      the exact mechanism remains unclear. Using a panel of Rheb-deficient mouse
      embryonic fibroblasts (MEFs), we show that Rheb is indeed essential for the rapid
      increase of mTORC1 activity following stimulation with insulin or amino acids.
      However, mTORC1 activity is less severely reduced in Rheb-deficient MEFs in the
      continuous presence of serum or upon stimulation with serum. This remaining
      mTORC1 activity is blocked by depleting the cells for amino acids or imposing
      energy stress. In addition, MEK inhibitors and the RSK-inhibitor BI-D1870
      interfere in mTORC1 activity, suggesting that RSK acts as a bypass for Rheb in
      activating mTORC1. Finally, we show that this rapamycin-sensitive, Rheb
      independent mTORC1 activity is important for cell cycle progression. In
      conclusion, whereas rapid adaptation in mTORC1 activity requires Rheb, a second
      Rheb-independent activation mechanism exists that contributes to cell cycle
      progression. 

PMID- 24303064
TI  - Aortopulmonary collateral flow is related to pulmonary artery size and affects
      ventricular dimensions in patients after the fontan procedure.
AB  - BACKGROUND: Aortopulmonary collaterals (APCs) are frequently found in patients
      with a single-ventricle (SV) circulation. However, knowledge about the clinical
      significance of the systemic-to-pulmonary shunt flow in patients after the
      modified Fontan procedure and its potential causes is limited. Accordingly, the
      aim of our study was to detect and quantify APC flow using cardiovascular
      magnetic resonance (CMR) and assess its impact on SV volume and function as well
      as to evaluate the role of the size of the pulmonary arteries in regard to the
      development of APCs. METHODS: 60 patients (mean age 13.3 +/- 6.8 years) after the
      Fontan procedure without patent tunnel fenestration underwent CMR as part of
      their routine clinical assessment that included ventricular functional analysis
      and flow measurements in the inferior vena cava (IVC), superior vena cava (SVC)
      and ascending aorta (Ao). APC flow was quantified using the systemic flow
      estimator: (Ao) - (IVC + SVC). Pulmonary artery index (Nakata index) was
      calculated as RPA + LPA area/body surface area using contrast enhanced MR
      angiography. The patient cohort was divided into two groups according to the
      median APC flow: group 1 < 0.495 l/min/m(2) and group 2 > 0.495 l/min/m(2).
      RESULTS: Group 1 patients had significant smaller SV enddiastolic (71 +/- 16 vs
      87 +/- 25 ml/m(2); p=0.004) and endsystolic volumes (29 +/- 11 vs 40 +/- 21
      ml/m(2); p=0.02) whereas ejection fraction (59 +/- 9 vs 56 +/- 13%; p=0.38)
      differed not significantly. Interestingly, pulmonary artery size showed a
      significant inverse correlation with APC flow (r=-0.50, p=0.002). CONCLUSIONS:
      Volume load due to APC flow in Fontan patients affected SV dimensions, but did
      not result in an impairment of SV function. APC flow was related to small
      pulmonary artery size, suggesting that small pulmonary arteries represent a
      potential stimulus for the development of APCs.

PMID- 24303065
TI  - Respiratory syncytial virus induced type I IFN production by pDC is regulated by
      RSV-infected airway epithelial cells, RSV-exposed monocytes and virus specific
      antibodies.
AB  - Innate immune responses elicited upon virus exposure are crucial for the
      effective eradication of viruses, the onset of adaptive immune responses and for
      establishing proper immune memory. Respiratory syncytial virus (RSV) is
      responsible for a high disease burden in neonates and immune compromised
      individuals, causing severe lower respiratory tract infections. During primary
      infections exuberant innate immune responses may contribute to disease severity.
      Furthermore, immune memory is often insufficient to protect during RSV re
      exposure, which results in frequent symptomatic reinfections. Therefore,
      identifying the cell types and pattern recognition receptors (PRRs) involved in
      RSV-specific innate immune responses is necessary to understand incomplete
      immunity against RSV. We investigated the innate cellular response triggered upon
      infection of epithelial cells and peripheral blood mononuclear cells. We show
      that CD14(+) myeloid cells and epithelial cells are the major source of IL-8 and
      inflammatory cytokines, IL-6 and TNF-alpha, when exposed to live RSV Three routes
      of RSV-induced IFN-alpha production can be distinguished that depend on the cross
      talk of different cell types and the presence or absence of virus specific
      antibodies, whereby pDC are the ultimate source of IFN-alpha. RSV-specific
      antibodies facilitate direct TLR7 access into endosomal compartments, while in
      the absence of antibodies, infection of monocytes or epithelial cells is
      necessary to provide an early source of type I interferons, required to engage
      the IFN-alpha,beta receptor (IFNAR)-mediated pathway of IFN-alpha production by
      pDC. However, at high pDC density infection with RSV causes IFN-alpha production
      without the need for a second party cell. Our study shows that cellular context
      and immune status are factors affecting innate immune responses to RSV. These
      issues should therefore be addressed during the process of vaccine development
      and other interventions for RSV disease. 

PMID- 24303067
TI  - Functional response of a near-surface soil microbial community to a simulated
      underground CO2 storage leak.
AB  - Understanding the impacts of leaks from geologic carbon sequestration, also known
      as carbon capture and storage, is key to developing effective strategies for
      carbon dioxide (CO2) emissions management and mitigation of potential negative
      effects. Here, we provide the first report on the potential effects of leaks from
      carbon capture and storage sites on microbial functional groups in surface and
      near-surface soils. Using a simulated subsurface CO2 storage leak scenario, we
      demonstrate how CO2 flow upward through the soil column altered both the
      abundance (DNA) and activity (mRNA) of microbial functional groups mediating
      carbon and nitrogen transformations. These microbial responses were found to be
      seasonally dependent and correlated to shifts in atmospheric conditions. While
      both DNA and mRNA levels were affected by elevated CO2, they did not react
      equally, suggesting two separate mechanisms for soil microbial community response
      to high CO2 levels. The results did not always agree with previous studies on
      elevated atmospheric (rather than subsurface) CO2 using FACE (Free-Air CO2
      Enrichment) systems, suggesting that microbial community response to CO2 seepage
      from the subsurface might differ from its response to atmospheric CO2 increases. 

PMID- 24303066
TI  - Derivation of neural stem cells from human adult peripheral CD34+ cells for an
      autologous model of neuroinflammation.
AB  - Proinflammatory factors from activated T cells inhibit neurogenesis in adult
      animal brain and cultured human fetal neural stem cells (NSC). However, the role
      of inhibition of neurogenesis in human neuroinflammatory diseases is still
      uncertain because of the difficulty in obtaining adult NSC from patients. Recent
      developments in cell reprogramming suggest that NSC may be derived directly from
      adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by
      transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c
      Myc and Klf4. The derived NSC could be differentiated to glial cells and action
      potential firing neurons. Co-culturing NSC with activated autologous T cells or
      treatment with recombinant granzyme B caused inhibition of neurogenesis as
      indicated by decreased NSC proliferation and neuronal differentiation. Thus, we
      have established a unique autologous in vitro model to study the pathophysiology
      of neuroinflammatory diseases that has potential for usage in personalized
      medicine. 

PMID- 24303068
TI  - Bone marrow-derived microglia infiltrate into the paraventricular nucleus of
      chronic psychological stress-loaded mice.
AB  - BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly
      react to infection or inflammation. The pathophysiological role of bone marrow
      derived microglia is of particular interest because they affect neurodegenerative
      disorders and neuropathic pain. The hypothesis of the current study is that
      chronic psychological stress (chronic PS) induces the infiltration of bone marrow
      derived microglia into hypothalamus by means of chemokine axes in brain and bone
      marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia
      specifically infiltrate the paraventricular nucleus (PVN) of mice that received
      chronic PS. Bone marrow derived-microglia are CX3CR1(low)CCR2(+)CXCR4(high), as
      distinct from CX3CR1(high)CCR2(-)CXCR4(low) resident microglia, and express
      higher levels of interleukin-1beta (IL-1beta) but lower levels of tumor necrosis
      factor-alpha (TNF-alpha). Chronic PS stimulates the expression of monocyte
      chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor
      1 (SDF-1) in the bone marrow and increases the frequency of CXCR4(+) monocytes in
      peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a
      beta3-adrenoceptor blockade prevents infiltration of bone marrow-derived
      microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone
      marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis
      in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

PMID- 24303069
TI  - The enterocyte-associated intestinal microbiota of breast-fed infants and adults
      responds differently to a TNF-alpha-mediated pro-inflammatory stimulus.
AB  - Co-evolved as an integral component of our immune system, the gut microbiota
      provides specific immunological services at different ages, supporting the immune
      education during our infancy and sustaining a well-balanced immunological
      homeostasis during the course of our life. In order to figure out whether this
      involves differences in the microbial groups primarily interacting with the host
      immune system, we developed a non-invasive HT29 cell-based minimal model to
      fingerprint the enterocyte-associated microbiota fraction in infants and adults.
      After depicting the fecal microbial community of 12 breast-fed infants and 6
      adults by 16S rDNA amplicon pools 454 pyrosequencing, their respective HT29 cell
      associated gut microbiota fractions were characterized by the universal
      phylogenetic array platform HTF-Microbi.Array, both in the presence and absence
      of a tumor necrosis factor-alpha (TNF-alpha)-mediated pro-inflammatory stimulus.
      Our data revealed remarkable differences between the enterocyte-associated
      microbiota fractions in breast-fed infants and adults, being dominated by
      Bifidobacterium and Enterobacteriaceae the first and Bacteroides-Prevotella and
      Clostridium clusters IV and XIVa the second. While in adults TNF-alpha resulted
      in a profound impairment of the structure of the enterocyte-associated microbiota
      fraction, in infants it remained unaffected. Differently from the adult-type gut
      microbial community, the infant-type microbiota is structured to cope with
      inflammation, being co-evolved to prime the early immune response by means of
      transient inflammatory signals from gut microorganisms. 

PMID- 24303071
TI  - Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/beta-catenin
      pathway in a Drosophila model for intellectual disability.
AB  - We recently reported that duplication of the E3 ubiquitin ligase HUWE1 results in
      intellectual disability (ID) in male patients. However, the underlying molecular
      mechanism remains unknown. We used Drosophila melanogaster as a model to
      investigate the effect of increased HUWE1 levels on the developing nervous
      system. Similar to the observed levels in patients we overexpressed the HUWE1
      mRNA about 2-fold in the fly. The development of the mushroom body and
      neuromuscular junctions were not altered, and basal neurotransmission was
      unaffected. These data are in agreement with normal learning and memory in the
      courtship conditioning paradigm. However, a disturbed branching phenotype at the
      axon terminals of the dorsal cluster neurons (DCN) was detected. Interestingly,
      overexpression of HUWE1 was found to decrease the protein levels of dishevelled
      (dsh) by 50%. As dsh as well as Fz2 mutant flies showed the same disturbed DCN
      branching phenotype, and the constitutive active homolog of beta-catenin,
      armadillo, could partially rescue this phenotype, our data strongly suggest that
      increased dosage of HUWE1 compromises the Wnt/beta-catenin pathway possibly by
      enhancing the degradation of dsh. 

PMID- 24303072
TI  - Functional difference between sustained and transient modulations of cognitive
      control in the simon task: evidence from false alarm responses on no-go trials.
AB  - Cognitive control in response compatibility tasks is modulated by the task
      context. Two types of contextual modulations have been demonstrated; sustained
      (block-wise) and transient (trial-by-trial). Recent research suggests that these
      modulations have different underlying mechanisms. This study presents new
      evidence supporting this claim by comparing false alarm (FA) responses on no-go
      trials of the Simon task between the sustained and transient contexts. In
      Experiment 1, the sustained context was manipulated so that a block included a
      larger number of incongruent trials. Results showed that participants made more
      FA responses by the hand opposite to the stimulus location. This suggests a
      generation of response bias in which the task-irrelevant location information is
      utilized in a reversed manner (i.e., to respond with the right hand to a stimulus
      presented on the left side and vice versa). Next, Experiment 2 examined the
      effect of the transient context and found that overall FA rate was lower when a
      no-go trial was preceded by an incongruent trial than by a congruent trial,
      whereas such response bias as that shown in Experiment 1 was not demonstrated.
      This suggests that the transient conflict context enhances inhibition of the task
      irrelevant process but does not make the task-irrelevant information actively
      usable. Based on these results, we propound two types of cognitive control
      modulations as adaptive behaviors: response biasing based on utilization of the
      task-irrelevant information under the sustained conflict context and transient
      enhancement of inhibition of the task-irrelevant process based on the online
      conflict monitoring. 

PMID- 24303070
TI  - WNT3 inhibits cerebellar granule neuron progenitor proliferation and
      medulloblastoma formation via MAPK activation.
AB  - During normal cerebellar development, the remarkable expansion of granule cell
      progenitors (GCPs) generates a population of granule neurons that outnumbers the
      total neuronal population of the cerebral cortex, and provides a model for
      identifying signaling pathways that may be defective in medulloblastoma. While
      many studies focus on identifying pathways that promote growth of GCPs, a
      critical unanswered question concerns the identification of signaling pathways
      that block mitogenic stimulation and induce early steps in differentiation. Here
      we identify WNT3 as a novel suppressor of GCP proliferation during cerebellar
      development and an inhibitor of medulloblastoma growth in mice. WNT3, produced in
      early postnatal cerebellum, inhibits GCP proliferation by down-regulating pro
      proliferative target genes of the mitogen Sonic Hedgehog (SHH) and the bHLH
      transcription factor Atoh1. WNT3 suppresses GCP growth through a non-canonical
      Wnt signaling pathway, activating prototypic mitogen-activated protein kinases
      (MAPKs), the Ras-dependent extracellular-signal-regulated kinases 1/2 (ERK1/2)
      and ERK5, instead of the classical beta-catenin pathway. Inhibition of MAPK
      activity using a MAPK kinase (MEK) inhibitor reversed the inhibitory effect of
      WNT3 on GCP proliferation. Importantly, WNT3 inhibits proliferation of
      medulloblastoma tumor growth in mouse models by a similar mechanism. Thus, the
      present study suggests a novel role for WNT3 as a regulator of neurogenesis and
      repressor of neural tumors. 

PMID- 24303073
TI  - Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction
      in ALS mice.
AB  - BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic
      intermittent hypoxia. However, all previous experimental studies on the effects
      of hypoxia in ALS have only used a sustained hypoxia model and it is possible
      that chronic intermittent hypoxia exerts effects via a different molecular
      mechanism from that of sustained hypoxia. No study has yet shown that hypoxia
      (either chronic intermittent or sustained) can affect the loss of motor neurons
      or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the
      effects of chronic intermittent hypoxia on motor and cognitive function in ALS
      mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups
      and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The
      effects of chronic intermittent hypoxia on ALS mice were evaluated using the
      rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in
      the ventral horn of the spinal cord were counted and western blot analyses were
      performed for markers of oxidative stress and inflammatory pathway activation.
      RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that
      experienced chronic intermittent hypoxia had poorer motor learning on the rotarod
      test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and
      fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild
      type mice, ALS mice that experienced chronic intermittent hypoxia had higher
      levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent
      hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably
      cognitive dysfunction in ALS mice. The generation of oxidative stress with
      activation of inflammatory pathways may be associated with this mechanism. Our
      study will provide insight into the association of hypoxia with disease
      progression, and in turn, the rationale for an early non-invasive ventilation
      treatment in patients with ALS.

PMID- 24303075
TI  - Discriminating between medium-sized Tridactyl Trackmakers: tracking Ornithopod
      tracks in the base of the Cretaceous (Berriasian, Spain).
AB  - BACKGROUND: Recent work on the Jurassic-Cretaceous transition of the Iberian
      Range (Spain) has opened a new window onto the interpretation of the trackmakers
      of some medium-sized tridactyl tracks. The ichnotaxon Therangospodus oncalensis
      has been described in the Huerteles Formation (Berriasian) and is one of the
      classical tracks from the area assigned to medium-sized theropods.
      METHODOLOGY/PRINCIPAL FINDINGS: A review of the type locality of Therangospodus
      oncalensis (Fuentesalvo tracksite) and other tracksites from the Huerteles
      Formation (Berriasian) has yielded new information on the morphology, gait and
      trackmaker identity of the aforementioned ichnospecies. The new data suggest that
      the trackmaker is an ornithopod rather than a theropod on the basis of the
      length/width ratio, the anterior triangle length-width ratio, the short steps,
      the round to quadrangular heel pad impression and the probable manus impressions.
      CONCLUSIONS/SIGNIFICANCE: T. oncalensis shows similarities with various tracks
      from the Berriasian of Europe assigned to Iguanodontipus. The ichnotaxonomical
      status of this ichnospecies is here considered as Iguanodontipus? oncalensis due
      to the current state of knowledge of the ichnotaxonomy of medium-sized ornithopod
      tracks. This reassessment of I? oncalensis also has two significant implications
      for the palaeoecology of the faunas during the deposition of the Huerteles
      Formation: 1- the high number and percentage of theropod tracks would be lower
      than previous papers have suggested. 2- the gregarious behaviour described in the
      type locality (Fuentesalvo) would be among ornithopods instead of theropods.

PMID- 24303074
TI  - Topoisomerase I inhibitors, shikonin and topotecan, inhibit growth and induce
      apoptosis of glioma cells and glioma stem cells.
AB  - Gliomas, the most malignant form of brain tumors, contain a small subpopulation
      of glioma stem cells (GSCs) that are implicated in therapeutic resistance and
      tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a
      crucial role in anti-cancer therapies. After isolated and identified the GSCs
      from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were
      administrated with various concentrations of shikonin or topotecan at different
      time points to seek for the optimal administration concentration and time point.
      The cell viability, cell cycle and apoptosis were detected using cell counting
      kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and
      GSCs. We demonstrated that shikonin and topotecan obviously inhibited
      proliferation of not only human glioma cells but also GSCs in a dose- and time
      dependent manner. According to the IC50 values at 24 h, 2 MUmol/L of shikonin and
      3 MUmol/L of topotecan were selected as the optimal administration concentration.
      In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S
      phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the
      activation of caspase 9/3-dependent pathway was involved in the apoptosis
      process. Therefore, the above results showed that topoisomerase I inhibitors,
      shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as
      glioma cells, which suggested that they might be the potential anticancer agents
      targeting gliomas to provide a novel therapeutic strategy. 

PMID- 24303076
TI  - Stakeholder perspectives and values when setting waterbird population targets:
      implications for flyway management planning in a European context.
AB  - Managing and controlling wildlife species within Europe is an acknowledged part
      of conservation management, yet deciding and setting a population target in order
      to control a population is perceived to be conceptually very challenging. We
      interviewed stakeholders, within a variety of governmental and non-governmental
      organizations, to evaluate their perspectives about setting population targets as
      part of waterbird management for controlling population sizes. We conclude that
      the setting of a quantifiable population target is beneficial as a measurable
      objective for monitoring and evaluating management actions. However, it must be
      recognised as just one possible measurable objective and there may well be
      multiple supporting objectives that encapsulate the management aims of different
      stakeholders. When considering wide-scale control of waterbirds species, where it
      is likely that population size matters, any population target should be coupled
      to the issues being addressed. We highlight that it is important to actively
      engage with stakeholders as part of the decision-making process, not only to gain
      consensus but to share knowledge. A clear understanding of the context and the
      rationale for controlling a waterbird species is needed to align the interests of
      diverse stakeholders. The provision of scientific data and the continuous
      monitoring of management actions is viewed as beneficial and demanded by
      stakeholders, as part of any decision-making process when setting population
      targets. This facilitates effective evaluation of management actions, helping
      managers make wise decisions as well as enabling the continued development of
      management plans. 

PMID- 24303077
TI  - The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are
      required in early embryogenesis.
AB  - Nuclear factor Y (NF-Y) is a trimeric transcription factor composed of three
      distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y
      subunits are known to play roles in many processes, such as gametogenesis,
      embryogenesis, seed development, drought resistance, ABA signaling, flowering
      time, primary root elongation, Endoplasmic Reticulum (ER) stress response and
      blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8
      genes control early embryogenesis. Detailed GUS and in situ analyses showed that
      NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the
      highest expression being during embryo development from the globular to the
      torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not
      display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants
      are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos
      fail to undergo to the heart stage and develop into abnormal globular embryos
      with both proembryo and suspensor characterized by a disordered cell cluster with
      an irregular shape, suggesting defects in embryo development. The suppression of
      both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective
      embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas
      complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8
      embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis.
      Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker
      line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8
      affect auxin response in early developing embryos. Our findings indicate that NF
      YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis
      of Arabidopsis thaliana. 

PMID- 24303078
TI  - Changes in the expression of miR-381 and miR-495 are inversely associated with
      the expression of the MDR1 gene and development of multi-drug resistance.
AB  - Multidrug resistance (MDR) frequently develops in cancer patients exposed to
      chemotherapeutic agents and is usually brought about by over-expression of P
      glycoprotein (P-gp) which acts as a drug efflux pump to reduce the intracellular
      concentration of the drug(s). Thus, inhibiting P-gp expression might assist in
      overcoming MDR in cancer chemotherapy. MiRNAome profiling using next-generation
      sequencing identified differentially expressed microRNAs (miRs) between parental
      K562 cells and MDR K562 cells (K562/ADM) induced by adriamycin treatment. Two
      miRs, miR-381 and miR-495, that were strongly down-regulated in K562/ADM cells,
      are validated to target the 3'-UTR of the MDR1 gene. These miRs are located
      within a miR cluster located at chromosome region 14q32.31, and all miRs in this
      cluster appear to be down-regulated in K562/ADM cells. Functional analysis
      indicated that restoring expression of miR-381 or miR-495 in K562/ADM cells was
      correlated with reduced expression of the MDR1 gene and its protein product, P
      gp, and increased drug uptake by the cells. Thus, we have demonstrated that
      changing the levels of certain miR species modulates the MDR phenotype in
      leukemia cells, and propose further exploration of the use of miR-based therapies
      to overcome MDR. 

PMID- 24303079
TI  - Evaluation of the spermicidal and contraceptive activity of Platycodin D, a
      Saponin from Platycodon grandiflorum.
AB  - BACKGROUND: The extract of Platycodon grandiflorum has been reported to have
      effective spermicidal activity. This study was designed to evaluate the
      spermicidal and contraceptive activity, as well as the safety, of Platycodin D
      (PD), a major saponin in Platycodon grandiflorum. METHODS: Using the computer
      aided sperm analysis (CASA) test criteria, the sperm-immobilizing activity of PD
      was studied using highly motile human sperm. The sperm viability was assessed by
      fluorescent staining using SYBR-14 (living sperm) and propidium iodide (dead
      sperm). The sperm membrane integrity was assessed by evaluating the hypo-osmotic
      swelling (HOS) and examinations by transmission electron microscopy (TEM) and
      scanning electron microscopy (SEM). The in vivo contraceptive efficacy was
      evaluated in rats using post-intrauterine PD application. The comet assay was
      employed to determine whether PD caused DNA damage in the sperm. Vaginal biopsies
      were also performed to determine whether the PD gel induced vaginal inflammation.
      RESULTS: A dose-dependent effect of PD on the sperm motility and viability was
      observed. The maximum spermicidal effect was observed with a 0.25 mM
      concentration of PD. More than 70% of the PD-treated sperm lost their HOS
      responsiveness at a concentration of 0.20 mM PD, indicating that PD caused injury
      to the sperm plasma membrane. TEM and SEM revealed significant damage to both the
      head and tail membranes of the sperm. PD decreased the fertility to zero in rats,
      was non-DNA damaging and was not harmful to the vaginal tissue in the rats.
      CONCLUSION: PD has significant spermicidal activity that should be explored in
      further studies.

PMID- 24303080
TI  - The cytohesin coiled-coil domain interacts with threonine 276 to control membrane
      association.
AB  - Cell migration is regulated by a number of small GTPases, including members of
      the Arf family. Cytohesins, a family of Arf-activating proteins, have been
      extensively implicated in the regulation of Arfs during migration and cell shape
      change. Membrane association of both the Arf and its activating protein is a
      prerequisite for Arf activation. Therefore regulating the extent of cytohesin
      membrane association is a mechanism for controlling the initiation of cell
      movement. We have discovered a novel intramolecular interaction that controls the
      association of cytohesins with membranes. The presence of the coiled-coil domain
      reduces the association of cytohesin 2 with membranes. We demonstrate that this
      domain interacts with more C-terminal regions of the protein. This interaction is
      independent of another previously identified autoinhibitory conformation. A
      threonine residue (T276) in the cytohesin 2 PH domain is a target for
      phosphorylation by Akt. Mutation of this threonine to aspartic acid, to mimic
      phosphorylation, disrupts the binding of the coiled-coil domain to c-terminal
      regions and promotes membrane association of cytohesin 2. The presence of a
      second autoinhibitory interaction in the cytohesins suggests that these proteins
      can act a signal integrators that stimulate migration only after receive multiple
      pro-migratory signals. 

PMID- 24303081
TI  - The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and
      protects the pancreas against zinc toxicity.
AB  - BACKGROUND: ZIP5 localizes to the baso-lateral membranes of intestinal
      enterocytes and pancreatic acinar cells and is internalized and degraded
      coordinately in these cell-types during periods of dietary zinc deficiency. These
      cell-types are thought to control zinc excretion from the body. The baso-lateral
      localization and zinc-regulation of ZIP5 in these cells are unique among the 14
      members of the Slc39a family and suggest that ZIP5 plays a role in zinc
      excretion. METHODS/PRINCIPAL FINDINGS: We created mice with floxed Zip5 genes and
      deleted this gene in the entire mouse or specifically in enterocytes or acinar
      cells and then examined the effects on zinc homeostasis. We found that ZIP5 is
      not essential for growth and viability but total knockout of ZIP5 led to
      increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired
      accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of
      function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in
      mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally,
      loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed
      a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation
      of (67)zinc. Retention of pancreatic (67)zinc was impaired in these mice but the
      absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and
      exacerbated the formation of large cytoplasmic vacuoles containing secretory
      protein in acinar cells. CONCLUSIONS: These studies demonstrate that ZIP5
      participates in the control of zinc excretion in mice. Specifically, they reveal
      a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for
      pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in
      acinar cells to protect against zinc-induced acute pancreatitis and attenuate the
      process of zymophagy. This suggests that it may play a role in autophagy.

PMID- 24303082
TI  - Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and
      mTNFR1 protect against fulminant hepatic failure in mice.
AB  - Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has a poor
      prognosis with high in-hospital mortality. Hepatic and circulating inflammatory
      cytokines, such as fibrinogen like protein 2 (fgl2), FasL/Fas, and
      TNFalpha/TNFR1, play a significant role in the pathophysiology of ACLF. This
      study aimed to investigate the therapeutic effect of recombinant adenoviral
      vectors carrying constructed DNA code for non-native microRNA (miRNA) targeting
      mouse fgl2 (mfgl2) or both mFas and mTNFR1 on murine hepatitis virus (MHV)-3
      induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic
      expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their
      inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas
      mTNFR1- miRNA,which expresses miRNA against both mFas and mTNFR1
      simultaneously,was constructed. To construct a miRNA adenovirus expression vector
      against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas
      mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were
      delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the
      therapeutic effect. 8 of 18 (44.4%) mice recovered from fulminant viral hepatitis
      in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1
      miRNA. But only 4 of 18 (22.2%) mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7%)
      mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors
      significantly ameliorated inflammatory infiltration, fibrin deposition,
      hepatocyte necrosis and apoptosis, and prolonged survival time. Our data
      illustrated that combined interference using adenovirus-mediated artificial
      miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic
      potential for the treatment of fulminant hepatitis. 

PMID- 24303083
TI  - Nasal carriage of methicillin-resistant Staphylococcus aureus among pediatricians
      in Taiwan.
AB  - BACKGROUND: Health care workers (HCWs) are at the interface between hospitals and
      communities. The survey for methicillin-resistant Staphylococcus aureus (MRSA)
      carriage among HCWs has mostly been conducted to investigate outbreaks or
      endemics. Community-associated MRSA are prevalent among children in Taiwan. We
      conducted this study to better understand the carriage rate of MRSA among
      pediatricians in non-outbreak situations in Taiwan,. METHODS: A total of 220
      pediatricians from Taiwan who attended the annual meeting of Taiwan Pediatric
      Association in April, 2010 were recruited to participate in this study and were
      sampled from the nares for the detection of MRSA by polymerase chain reaction
      (PCR) and further by culture. The following molecular analyses were performed,
      including pulsed-field gel electrophoresis (PFGE), multilocus sequence typing
      (MLST), typing of staphylococcal cassette chromosome mec (SCCmec) and the
      presence of Panton-Valentine leukocidin (PVL) genes. RESULTS: MRSA was detected
      from 15 attendees (6.8%) by PCR. MRSA-colonized attendees had a significantly
      lower rate (0.041) of working in the medical center, while borderline
      significantly higher rate of working in the Regional Hospital (p=0.056), than
      those without MRSA colonization. From those 15 samples, 12 MRSA isolates were
      identified by culture and molecularly characterized. Three PFGE patterns, two
      sequence types (ST 59, ST 508), and two SCCmec types (IV and VT) were identified,
      respectively. Five isolates, including three carrying SCCmec types VT, were PVL
      positive. All 12 isolates were susceptible to vancomycin, teicoplanin, linezolid,
      fusidic acid, trimethoprim/sulfamethoxazole, and doxycyclin, and resistant to
      penicillin. CONCLUSION/SIGNIFICANCE: Around seven percent of pediatricians in
      Taiwan harbored CA-MRSA in their nares.

PMID- 24303084
TI  - Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette
      transporters and activates the mitochondrial apoptosis pathway via beta
      catenin/GSK-3beta modulation in colorectal carcinoma.
AB  - Multidrug resistance (MDR), an unfavorable factor compromising the treatment
      efficacy of anticancer drugs, involves the upregulation of ATP binding cassette
      (ABC) transporters and induction of galectin-3 signaling. Galectin-3 plays an
      anti-apoptotic role in many cancer cells and regulates various pathways to
      activate MDR. Thus, the inhibition of galectin-3 has the potential to enhance the
      efficacy of the anticancer drug epirubicin. In this study, we examined the
      effects and mechanisms of silencing galectin-3 via RNA interference (RNAi) on the
      beta-catenin/GSK-3beta pathway in human colon adenocarcinoma Caco-2 cells.
      Galectin-3 knockdown increased the intracellular accumulation of epirubicin in
      Caco-2 cells; suppressed the mRNA expression of galectin-3, beta-catenin, cyclin
      D1, c-myc, P-glycoprotein (P-gp), MDR-associated protein (MRP) 1, and MRP2; and
      downregulated the protein expression of P-gp, cyclin D1, galectin-3, beta
      catenin, c-Myc, and Bcl-2. Moreover, galectin-3 RNAi treatment significantly
      increased the mRNA level of GSK-3beta, Bax, caspase-3, and caspase-9; remarkably
      increased the Bax-to-Bcl-2 ratio; and upregulated the GSK-3beta and Bax protein
      expressions. Apoptosis was induced by galectin-3 RNAi and/or epirubicin as
      demonstrated by chromatin condensation, a higher sub-G1 phase proportion, and
      increased caspase-3 and caspase-9 activity, indicating an intrinsic/mitochondrial
      apoptosis pathway. Epirubicin-mediated resistance was effectively inhibited via
      galectin-3 RNAi treatment. However, these phenomena could be rescued after
      galectin-3 overexpression. We show for the first time that the silencing of
      galectin-3 sensitizes MDR cells to epirubicin by inhibiting ABC transporters and
      activating the mitochondrial pathway of apoptosis through modulation of the beta
      catenin/GSK-3beta pathway in human colon cancer cells. 

PMID- 24303085
TI  - Lupeol is one of active components in the extract of Chrysanthemum indicum Linne
      that inhibits LMP1-induced NF-kappaB activation.
AB  - We have previously reported that seventy percent ethanol extract of Chrysanthemum
      indicum Linne (CIE) strongly reduces Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cell line (LCL) survival by inhibiting virus-encoded latent
      infection membrane protein 1 (LMP1)-induced NF-kappaB activation. To identify an
      active compound(s) in CIE that inhibits LMP1-induced NF-kappaB activation,
      activity-guided fractionation was employed. The CH2Cl2 fraction of CIE strongly
      reduced LMP1-induced NF-kappaB activation and LCL viability with relatively low
      cytotoxic effects on primary human foreskin fibroblast (HFF), HeLa or Burkitt's
      lymphoma (BL41) cells. Furthermore, lupeol, a pentacyclic triterpene, was
      identified in the CH2Cl2 fraction of CIE to attenuate LMP1-induced NF-kappaB
      activation and LCL viability. This study demonstrates that lupeol is one of
      active compounds in the CH2Cl2 fraction of CIE that inhibits LMP1-induced NF
      kappaB activation and reduces NF-kappaB-dependent LCL viability. 

PMID- 24303087
TI  - Lipid peroxidation products in human health and disease.

PMID- 24303086
TI  - Hyperglycemia-induced inhibition of DJ-1 expression compromised the effectiveness
      of ischemic postconditioning cardioprotection in rats.
AB  - Ischemia postconditioning (IpostC) is an effective way to alleviate ischemia and
      reperfusion injury; however, the protective effects seem to be impaired in
      candidates with diabetes mellitus. To gain deep insight into this phenomenon, we
      explored the role of DJ-1, a novel oncogene, that may exhibit powerful
      antioxidant capacity in postconditioning cardioprotection in a rat model of
      myocardial ischemia reperfusion injury. Compared with normal group, cardiac DJ-1
      was downregulated in diabetes. Larger postischemic infarct size as well as
      exaggeration of oxidative stress was observed, while IpostC reversed the above
      changes in normal but not in diabetic rats. DJ-1 was increased after ischemia and
      postconditioning contributed to a further elevation; however, no alteration of DJ
      1 was documented in all subgroups of diabetic rats. Alteration of the
      cardioprotective PI3K/Akt signaling proteins may be responsible for the
      ineffectiveness of postconditioning in diabetes. There is a positive correlation
      relationship between p-Akt and DJ-1 but a negative correlation between infarct
      size and DJ-1, which may partially explain the interaction of DJ-1 and IpostC
      cardioprotection. Our result indicates a beneficial role of DJ-1 in myocardial
      ischemia reperfusion. Downregulation of cardiac DJ-1 may be responsible for the
      compromised diabetic heart responsiveness to IpostC cardioprotection. 

PMID- 24303088
TI  - Matching donor to recipient in liver transplantation: Relevance in clinical
      practice.
AB  - Achieving optimum outcomes after liver transplantation requires an understanding
      of the interaction between donor, graft and recipient factors. Within the cohort
      of patients waiting for a transplant, better matching of the donor organ to the
      recipient will improve transplant outcomes and benefit the overall waiting list
      by minimizing graft failure and need for re-transplantation. A PubMed search was
      conducted to identify published literature investigating the effects of donor
      factors such as age, gender, ethnicity, viral serology; graft factors such as
      size and quality, recipient factors such as age, size, gender and transplant
      factors such as major or minor blood group incompatibility and immunological
      factors. We also report technical and therapeutic modifications that can be used
      to manage donor-recipient mismatch identified from literature and the authors'
      clinical experience. Multiple donor and recipient factors impact graft survival
      after liver transplantation. Appropriate matching based on donor-organ-recipient
      variables, modification of surgical technique and innovative peri-transplant
      strategies can increase the donor pool by utilizing grafts from marginal donors
      that are traditionally turned down. 

PMID- 24303089
TI  - Hepatitis B virus reactivation with rituximab-containing regimen.
AB  - Rituximab is recognized as a useful drug for the treatment of B-cell non
      Hodgkin's lymphoma and its use has been extended to such diseases as idiopathic
      thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid
      arthritis and ANCA-associated vasculitides. One serious complication associated
      with its use is the reactivation of hepatitis B virus and the search for methods
      to prevent this occurrence has resulted in the rapid accumulation of knowledge.
      In this review, we discuss case analyses from our department and other groups and
      outline the current knowledge on the topic and the remaining issues. 

PMID- 24303090
TI  - Association between nonalcoholic fatty liver disease and acute ischemic stroke
      severity and outcome.
AB  - AIM: To evaluate the association of nonalcoholic fatty liver disease (NAFLD) with
      acute ischemic stroke severity and in-hospital outcome. METHODS: We prospectively
      studied all patients who were admitted in our Department with acute ischemic
      stroke between September 2010 and August 2012 (n = 415; 39.5% males, mean age
      78.8 +/- 6.6 years). The severity of stroke was assessed with the National
      Institutes of Health Stroke Scale (NIHSS) score at admission. NALFD was defined
      as serum alanine aminotransferase and/or aspartate aminotransferase levels above
      the upper limit of normal in the absence of other causes of elevated
      aminotransferases levels [chronic hepatitis B or C, drug toxicity, increased
      alcohol consumption (> 21 and > 14 drinks per week in men and women,
      respectively), cholestatic diseases or rhabdomyolysis]. The outcome was assessed
      with the modified Rankin scale (mRS) score at discharge and in-hospital
      mortality. Adverse outcome was defined as mRS score at discharge >= 2. Dependency
      at discharge was defined as mRS score between 2 to 5. RESULTS: NAFLD was present
      in 7.7% of the study population. Patients with NAFLD had lower serum high-density
      lipoprotein cholesterol and higher triglyceride levels than patients without
      NAFLD (P < 0.05 for both comparisons). Demographic data, the prevalence of other
      cardiovascular risk factors and the prevalence of established CVD did not differ
      between the two groups. At admission, the NIHSS score did not differ between
      patients with and without NAFLD (6.3 +/- 6.4 and 8.8 +/- 9.6, respectively; P =
      NS). At discharge, the mRS score did not differ between the two groups (1.9 +/-
      2.2 and 2.6 +/- 2.2 in patients with and without NAFLD, respectively; P = NS).
      Rates of dependency at discharge were also similar in patients with and without
      NAFLD (36.8% and 55.0%, respectively; P = NS) as were the rates of adverse
      outcome (42.9% and 58.6%, respectively; P = NS). In-hospital mortality rates also
      did not differ between the 2 groups (8.0% and 7.0% in patients with and without
      NAFLD, respectively; P = NS). CONCLUSION: The presence of NAFLD in patients
      admitted for acute ischemic stroke does not appear to be associated with more
      severe stroke or with worse in-hospital outcome.

PMID- 24303091
TI  - Increased bone mineral density in patients with non-alcoholic steatohepatitis.
AB  - AIM: To determine the relationship between non-alcoholic steatohepatitis (NASH)
      and bone mineral density (BMD). METHODS: A total of 38 patients (25 males) with a
      diagnosis of histologically proven NASH and 42 healthy controls (24 males) were
      enrolled in the study. Demographic features, clinical findings, complete blood
      count and routine biochemical analysis, as well as adrenal, thyroid and gonadal
      functions, were recorded. Additionally, intact parathormone, 25-OH-vitamin-D3,
      tumor necrosis factor-alpha, interleukin-6, interleukin-1, insulin-like growth
      factor-1 and insulin-like growth factor binding protein-3 levels were measured in
      both groups. Furthermore, lumbar spine and femoral neck BMD of both groups were
      measured by the dual-energy X-ray absorptiometry (DXA) method. RESULTS: The mean
      age was 41 +/- 12 years in the NASH group and 43 +/- 11 years in the control
      group. Among demographic features, waist circumference was significantly larger
      in the NASH group compared to the control group (P < 0.019). Among laboratory
      parameters, serum triglyceride (P < 0.008), alanine transaminase (P < 0.0001),
      aspartate transaminase (P < 0.001), alkaline phosphatase (P < 0.016), gamma
      glutamyl transferase (P < 0.0001), ferritin (P < 0.001) and 25-OH-vitamin-D3
      levels (P < 0.0001) were significantly higher in the NASH group compared to the
      control group. Lumbar BMD was significantly higher in the NASH group compared to
      the control group (1.057 +/- 0.119 g/cm(2) vs 0.941 +/- 0.133 g/cm(2); P < 0.001,
      respectively). In the NASH group, there was no significant relationship between
      BMD and fibrosis stage in liver biopsy. CONCLUSION: NASH increases BMD and may be
      related to an elevated serum 25-OH-vitamin D3 level.

PMID- 24303092
TI  - IL-28B polymorphisms and treatment response in hepatitis C virus patients with
      persistently normal alanine aminotransferase.
AB  - AIM: To examine the association between the interleukin 28B (IL-28B) genotype and
      treatment response in hepatitis C virus (HCV)-infected patients with persistently
      normal alanine aminotransferase (PNALT). METHODS: We compared the treatment
      response of HCV-infected patients with PNALT to that of patients with non-PNALT.
      Between February 2010 and April 2013, 278 patients infected with HCV were
      enrolled in this study. All of the patients were treated with peginterferon-alpha
      2a or 2b plus ribavirin. In addition, 180 MUg of peginterferon alpha-2a or 1.5
      MUg/kg peginterferon alpha-2b per week plus weight-based ribavirin (600-1000
      mg/d) were typically administered for 24 wk to HCV genotype 2-infected patients
      or for 48-72 wk to HCV genotype 1-infected patients. In all of the patients, the
      IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide
      polymorphism assay. HCV RNA was measured using the COBAS TaqMan HCV test.
      RESULTS: Female patients were dominant in the PNALT group (P < 0.0001). Among 72
      HCV genotype 1-infected patients with PNALT, the early virologic response (EVR)
      rates (P < 0.01) and the sustained virologic response (SVR) rates (P < 0.01) were
      higher in patients with the IL-28B TT genotype than in those with the IL-28B
      TG/GG genotype. In HCV genotype 1-infected patients with PNALT, multivariate
      logistic-regression analysis showed that SVR was independently predicted by the
      IL-28B rs8099917 TT type (P < 0.05) and having an EVR (P < 0.01). The IL-28B
      rs8099917 TT genotype strongly correlated with treatment response in HCV genotype
      1-infected Asian patients with PNALT. CONCLUSION: The IL-28B genotype may be
      useful for selecting HCV genotype 1-infected patients with PNALT who should
      receive interferon-based treatment.

PMID- 24303093
TI  - Homogeneous phenomenon of the graft when using different genotype characteristic
      of recipients/donors in living donor liver transplantation.
AB  - AIM: To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435
      and CYP3A4*18 of the liver graft after living donor liver transplantation (LDLT).
      METHODS: We identified the proportional change of the CYP3A5*3, MDR1-3435 and
      CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor
      with different genotype polymorphisms and 119 liver graft biopsy samples used
      with the pyrosequencing technique after LDLT. Polymerase chain reaction/ligase
      detection reaction assay and restriction fragment length polymorphism was
      employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide
      polymorphisms (SNPs). All of the recipients and donors expressed with the similar
      SNP genotype of CYP3A5*3, MDR1-3435 or CYP3A4*18 were excluded. RESULTS: The
      final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3, MDR1
      3435 and CYP3A4*18 was predominated depends on the donor with restriction
      fragment length polymorphism and seems to be less related to the recipient. The
      proportional changes of G to A alleles of the 119 samples of CYP3A5*3 (included A
      > A/G, A/G > A, A/G > G, G > A, G > A/G and A > G), C to T alleles of the 108
      samples of MDR1-3435 (included C > C/T, C/T > C, C/T > T, T > C/T and T > C), and
      T to C alleles of 15 samples of CYP3A4*18 (included T/C > T and T > C/T) were
      significant different between the recipients and the liver graft biopsy samples
      (P < 0.0001) and less difference when compared with the donors in the
      pyrosequencing analysis after LDLT. CONCLUSION: The CYP3A5*3, MDR1-3435 and
      CYP3A4*18 of the recipient could be modified by the donor so-called homogenous
      phenomenon when the recipient's blood drained into the liver graft.

PMID- 24303094
TI  - Diagnostic challenges of Wilson's disease presenting as acute pancreatitis,
      cholangitis, and jaundice.
AB  - Wilson's disease is a rare disorder of copper transport in hepatic cells, and may
      present as cholestatic liver disease; pancreatitis and cholangitis are rarely
      associated with Wilsons's disease. Moreover, cases of Wilson's disease presenting
      as pigmented gallstone pancreatitis have not been reported in the literature. In
      the present report, we describe a case of a 37-year-old man who was admitted with
      jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis,
      cholangitis, and obstructive jaundice caused by pigmented gallstones that were
      detected during retrograde cholangiopancreatography. However, because of his long
      term jaundice and the presence of pigmented gallstones, the patient underwent
      further evaluation for Wilson's disease, which was subsequently confirmed. This
      patient's unique presentation exemplifies the overlap in the clinical and
      laboratory parameters of Wilson's disease and cholestasis, and the difficulties
      associated with their differentiation. It suggests that Wilson's disease should
      be considered in patients with pancreatitis, cholangitis, and severe protracted
      jaundice caused by pigmented gallstones. 

PMID- 24303096
TI  - Bright future for physiological research in Physiological Reports.

PMID- 24303095
TI  - New approaches to manipulate minimal residual disease after allogeneic stem cell
      transplantation.
AB  - Minimal residual disease (MRD) is a complex topic that has been studied
      extensively in hematologic malignancies given its clinical implications related
      to prognosis. However, methods to monitor and treat MRD, especially after stem
      cell transplantation, are not well defined and vary in different disease
      processes. Alternative transplant strategies, such as reduced-intensity
      conditioning, have altered the way we assess and address MRD after
      transplantation. Development of new diagnostic tools have allowed for higher
      sensitivity and specificity of testing. Both targeted chemotherapeutic agents and
      immunotherapies have been developed to treat MRD in hopes of improving patient
      outcomes. This article aims to address ways to define and manipulate MRD
      specifically after stem cell transplantation.

PMID- 24303097
TI  - Adenosine diphosphate reduces infarct size and improves porcine heart function
      after myocardial infarct.
AB  - Acute myocardial infarction continues to be a major cause of morbidity and
      mortality. Timely reperfusion can substantially improve outcomes and the
      administration of cardioprotective substances during reperfusion is therefore
      highly attractive. Adenosine diphosphate (ADP) and uridine-5-triphoshate (UTP)
      are both released during myocardial ischemia, influencing hemodynamics. Both
      mediate the release of tissue plasminogen activator (t-PA), which can reduce
      infarct size (IS). The objective of this study was to investigate whether
      exogenous ADP and UTP administration during reperfusion could reduce myocardial
      IS and whether this correlated to t-PA release or improvements in hemodynamic
      responses. Hemodynamic variables and t-PA were measured in 22 pigs before,
      during, and after 45 min of left anterior coronary artery occlusion. During
      reperfusion, the pigs were randomized to 240 min of intracoronary infusion of
      ADP, UTP, or control (no intervention). Ischemic area compared to the area at
      risk [IS/AAR] was measured. [IS/AAR] was 52 +/- 11% in the control animals. ADP
      decreased [IS/AAR] by 19% (P < 0.05), while UTP increased [IS/AAR] by 15% (P <
      0.05). Cardiac output (CO) increased from 3.4 to 3.5 L/min (P < 0.05) and mean
      arterial pressure (MAP) decreased from 87 to 73 mmHg in the ADP group (P < 0.05).
      t-PA concentration increased in the ADP and UTP group from 2.0 ng/mL to 2.5 and
      2.4 ng/mL, respectively (P < 0.05) but remained unchanged in the control group.
      In conclusion, intracoronary ADP infusion during reperfusion reduces IS by ~20%
      independently from systemic release of t-PA. ADP-induced reduction in both
      preload and afterload could account for the beneficial myocardial effect. 

PMID- 24303098
TI  - Enhanced force production in old age is not a far stretch: an investigation of
      residual force enhancement and muscle architecture.
AB  - In older adults, isometric force production is enhanced following a voluntary
      lengthening contraction when compared with isometric force produced at the same
      muscle length without a prior lengthening contraction. This phenomenon is termed
      residual force enhancement (RFE), and appears to be related to the age-related
      maintenance of eccentric (ECC) strength. However, it is unknown whether age
      related changes in muscle architecture contribute to greater RFE at short and
      long muscle lengths in old age. Neuromuscular properties of the knee extensors
      were assessed on a HUMAC NORM dynamometer. Torque was examined in young (26 +/- 3
      year, n = 11) and old men (77 +/- 6 year, n = 11) during brief maximal voluntary
      isometric contractions (MVC) at 80 degrees  and 120 degrees  (180 degrees 
      representing full knee extension) and then compared with torque during a steady
      state phase at the same joint angle following a maximal voluntary lengthening
      contraction at 30 degrees /sec over a 60 degrees  joint excursion; either from
      140 to 80 degrees  (long), or from 180 to 120 degrees  (short). Ultrasound images
      were obtained from the vastus lateralis during the isometric phase for each
      condition. When comparing the ECC torque with the MVC isometric torque, old men
      had 17% greater ECC:MVC ratios than young men, confirming an age-related
      maintenance of ECC strength. The extent of RFE was greater at long versus short
      but independent of age. At rest, old had shorter (~18%) and less pennated (~22%)
      fascicles. However, changes in fascicle length and pennation during contraction
      did not contribute to RFE in either group. Thus, age-related changes in muscle
      architecture may not contribute to RFE. 

PMID- 24303099
TI  - Support vector machines classifiers of physical activities in preschoolers.
AB  - The goal of this study is to develop, test, and compare multinomial logistic
      regression (MLR) and support vector machines (SVM) in classifying preschool-aged
      children physical activity data acquired from an accelerometer. In this study, 69
      children aged 3-5 years old were asked to participate in a supervised protocol of
      physical activities while wearing a triaxial accelerometer. Accelerometer counts,
      steps, and position were obtained from the device. We applied K-means clustering
      to determine the number of natural groupings presented by the data. We used MLR
      and SVM to classify the six activity types. Using direct observation as the
      criterion method, the 10-fold cross-validation (CV) error rate was used to
      compare MLR and SVM classifiers, with and without sleep. Altogether, 58
      classification models based on combinations of the accelerometer output variables
      were developed. In general, the SVM classifiers have a smaller 10-fold CV error
      rate than their MLR counterparts. Including sleep, a SVM classifier provided the
      best performance with a 10-fold CV error rate of 24.70%. Without sleep, a SVM
      classifier-based triaxial accelerometer counts, vector magnitude, steps,
      position, and 1- and 2-min lag and lead values achieved a 10-fold CV error rate
      of 20.16% and an overall classification error rate of 15.56%. SVM supersedes the
      classical classifier MLR in categorizing physical activities in preschool-aged
      children. Using accelerometer data, SVM can be used to correctly classify
      physical activities typical of preschool-aged children with an acceptable
      classification error rate. 

PMID- 24303100
TI  - Elevated pulmonary arterial pressure and altered expression of Ddah1 and Arg1 in
      mice lacking cavin-1/PTRF.
AB  - Caveolae are invaginations in the plasma membrane that depend on caveolins and
      cavins for maturation. Here, we investigated the pulmonary phenotype in mice
      lacking cavin-1. Bright field and electron-microscopy showed that the cavin-1
      deficient mice lacked caveolae in the lung, had an increased lung tissue density,
      and exhibited hypertrophic remodeling of pulmonary arteries. The right ventricle
      of the heart moreover had an increased mass and the right ventricular pressure
      was elevated. A microarray analysis revealed upregulation of Arg1 and
      downregulation of Ddah1, molecules whose altered expression has previously been
      associated with pulmonary arterial hypertension. Taken together, this work
      demonstrates vascular remodeling and increased pulmonary blood pressure in cavin
      1 deficient mice and associates this phenotype with altered expression of Arg1
      and Ddah1. 

PMID- 24303101
TI  - Dietary saturated fat and docosahexaenoic acid differentially effect cardiac
      mitochondrial phospholipid fatty acyl composition and Ca(2+) uptake, without
      altering permeability transition or left ventricular function.
AB  - High saturated fat diets improve cardiac function and survival in rodent models
      of heart failure, which may be mediated by changes in mitochondrial function.
      Dietary supplementation with the n3-polyunsaturated fatty acid docosahexaenoic
      acid (DHA, 22:6n3) is also beneficial in heart failure and can affect
      mitochondrial function. Saturated fatty acids and DHA likely have opposing
      effects on mitochondrial phospholipid fatty acyl side chain composition and
      mitochondrial membrane function, though a direct comparison has not been
      previously reported. We fed healthy adult rats a standard low-fat diet (11% of
      energy intake from fat), a low-fat diet supplemented with DHA (2.3% of energy
      intake) or a high-fat diet comprised of long chain saturated fatty acids (45%
      fat) for 6 weeks. There were no differences among the three diets in cardiac mass
      or function, mitochondrial respiration, or Ca(2+)-induced mitochondrial
      permeability transition. On the other hand, there were dramatic differences in
      mitochondrial phospholipid fatty acyl side chains. Dietary supplementation with
      DHA increased DHA from 7% to ~25% of total phospholipid fatty acids in
      mitochondrial membranes, and caused a proportional depletion of arachidonic acid
      (20:4n6). The saturated fat diet increased saturated fat and DHA in mitochondria
      and decreased linoleate (18:2n6), which corresponded to a decrease in Ca(2+)
      uptake by isolated mitochondria compared to the other diet groups. In conclusion,
      despite dramatic changes in mitochondrial phospholipid fatty acyl side chain
      composition by both the DHA and high saturated fat diets, there were no effects
      on mitochondrial respiration, permeability transition, or cardiac function. 

PMID- 24303102
TI  - Effect of acute hyperthyroidism on blood flow, muscle oxygenation, and
      sympathetic nerve activity during dynamic handgrip.
AB  - Hyperthyroidism induces marked changes in hemodynamics. Although considerable
      research has been done to study the effect of hyperthyroidism on the
      cardiovascular system, few studies have isolated the short-term, nongenomic
      effects of thyroid hormone on cardiovascular responses to exercise. We used near
      infrared spectroscopy to measure muscle oxygenation, Doppler ultrasound to
      measure skeletal muscle blood flow, and microneurography to measure muscle
      sympathetic nerve activity (MSNA) during fatiguing dynamic handgrip in twelve
      healthy males (26 +/- 1 years). Subjects were measured separately in both the
      euthyroid state, and acute hyperthyroid state (approximately ten times the normal
      levels of T3), induced by oral dosage of 300 MUg of triiodothyronine (T3).
      Forearm blood flow was increased as a function of exercise time in the euthyroid
      and hyperthyroid state (Delta161.8 +/- 45.0 mL/min and Delta140.7 +/- 16.3
      mL/min, respectively) but there was no significant difference between trials.
      Forearm vascular conductance (FVC) also increased as a function of exercise time
      with no significant difference between treatments at submaximal exercise but was
      significantly less with T3 treatment. MSNA was not different at rest or during
      submaximal exercise; however, MSNA was significantly greater at fatigue during
      the hyperthyroid state. Muscle oxyhemoglobin concentration was decreased during
      exercise in both euthyroid and hyperthyroid states (Delta19.7 +/- 10.8% and
      Delta14.8 +/- 9.6%, respectively); whereas deoxyhemoglobin concentration was
      increased (Delta50.0 +/- 4.1% and Delta50.0 +/- 6.2%, respectively). These
      results indicate that T3 had no direct effect on skeletal muscle oxygenation or
      blood flow during dynamic exercise, but elicited greater MSNA and lower FVC
      during fatiguing exercise. 

PMID- 24303103
TI  - Animal model of simulated microgravity: a comparative study of hindlimb unloading
      via tail versus pelvic suspension.
AB  - The aim of this study was to compare physiological effects of hindlimb suspension
      (HLS) in tail- and pelvic-HLS rat models to determine if severe stretch in the
      tail-HLS rats lumbosacral skeleton may contribute to the changes traditionally
      attributed to simulated microgravity and musculoskeletal disuse in the tail-HLS
      model. Adult male Sprague-Dawley rats divided into suspended and control
      nonsuspended groups were subjected to two separate methods of suspension and
      maintained with regular food and water for 2 weeks. Body weights, food and water
      consumption, soleus muscle weight, tibial bone mineral density, random plasma
      insulin, and hindlimb pain on pressure threshold (PPT) were measured. X-ray
      analysis demonstrated severe lordosis in tail- but not pelvic-HLS animals.
      However, growth retardation, food consumption, and soleus muscle weight and
      tibial bone density (decreased relative to control) did not differ between two
      HLS models. Furthermore, HLS rats developed similar levels of insulinopenia and
      mechanical hyperalgesia (decreased PPT) in both tail- and pelvic-HLS groups. In
      the rat-to-rat comparisons, the growth retardation and the decreased PPT observed
      in HLS-rats was most associated with insulinopenia. In conclusion, these data
      suggest that HLS results in mild prediabetic state with some signs of pressure
      hyperalgesia, but lumbosacral skeleton stretch plays little role, if any, in
      these pathological changes. 

PMID- 24303104
TI  - The distribution of the preferred directions of the ON-OFF direction selective
      ganglion cells in the rabbit retina requires refinement after eye opening.
AB  - The ON-OFF direction selective ganglion cells (DSGCs) in the mammalian retina
      respond differentially for an object moving in different directions. DSGCs can be
      further segregated into four functional subtypes, namely those responsible for
      the detection of motion in the superior, inferior, anterior, and posterior
      directions of the visual field. Although it has been known that the basic neural
      circuit of direction selectivity is established at around the time of eye
      opening, it is less known if the four DSGC subtypes can be unambiguously
      distinguished at this time and whether their preferred directions are aligned
      with four canonical axes at this developmental stage. By examining the preferred
      directions of DSGCs in P10-12 rabbit retinas and characterizing their
      distribution pattern, we have shown that the preferred directions of DSGCs at
      around the time of eye opening are not distinctly segregated but rather are
      diffusely distributed along the four canonical axes. Similar results were found
      in the mouse retina by reanalyzing previously published data. Furthermore, taking
      into account the fact that the direction tuning strength of DSGCs at P10-12 is
      weaker than that in adults, this was found not to be correlated with their
      preferred directions, which suggests that the maturations of direction
      selectivity and preferred direction are independent processes. In addition, we
      also found that the subtypes of DSGCs, which do not display tracer coupling
      pattern in the adult, show extensive coupling at P10-12. Taken together, the
      present study supports that the significant refinement after eye opening is
      required for the development of the four functional DSGC subtypes in the rabbit
      retina. 

PMID- 24303105
TI  - Thermoregulatory, cardiovascular, and metabolic responses to mild caloric
      restriction in the Brown Norway rat.
AB  - Caloric restriction (CR) has been demonstrated to prolong the life span of a
      variety of species. CR-induced reduction in core temperature (Tc) is considered a
      key mechanism responsible for prolonging life span in rodents; however, little is
      known about the regulation of CR-induced hypothermia as a function of the
      circadian cycle. We assessed how mild CR that resulted in a 10% reduction in body
      weight affected the 24 h patterns of Tc as well as heart rate (HR) and motor
      activity (MA) of the Brown Norway rat. Telemetered rats were allowed to feed for
      20 weeks ad libitum (AL) or given a CR diet. Tc, HR, and MA of CR rats exhibited
      nocturnal reductions and diurnal elevations, opposite to that of AL rats. The
      effects of CR appeared to peak at ~4 weeks. Metabolic rate (MR) and respiratory
      exchange ratio (RER) were measured overnight after 18 weeks of CR. MR and RER
      were elevated markedly at the time of feeding in CR rats and then declined during
      the night. We found that the pattern of Tc was altered with CR, characterized by
      elimination of high nocturnal Tc's typically observed in AL animals. In terms of
      mechanisms to prolong life span in CR animals, we suggest that the shift in the
      pattern of Tc during CR (i.e., elimination of high Tc's) may be as critical as
      the overall mean reduction in Tc. Future studies should address how the time of
      feeding may affect the thermoregulatory response in calorically restricted rats. 

PMID- 24303106
TI  - Force enhancement in lengthening contractions of cat soleus muscle in situ:
      transient and steady-state aspects.
AB  - Force enhancement (FE) associated with lengthening is a well-accepted phenomenon
      of active skeletal muscle, but the underlying mechanism(s) remain unknown.
      Similar to force depression (FD) following active shortening, the mechanism of FE
      may be attributed, at least in part, to cross-bridge kinetics. To examine this
      relationship, a post hoc analysis was performed on the transient force relaxation
      phase of previous in-situ FE experiments in soleus muscle-tendon units of
      anesthetized cats. For each muscle (n = 8), nine eccentric lengthenings (3
      amplitudes, 3 velocities) were performed while tetanically stimulated (3T at 30
      Hz, 3* alpha motorneuron, 35 +/- 1 degrees C). To determine transient aspects of
      FE, the period immediately following stretching was fit with an exponential decay
      function (R (2) > 0.95). Statistical analyses revealed that total steady-state FE
      (FESS) increased with stretching amplitude and applied mechanical work. A
      positive relationship was observed between the active FESS and rate of force
      decay (k), indicating that a kinetic mechanism may explain active FE. However,
      for all muscles and stretch conditions, there was no correlation between the
      total amount of FESS and rate of decay. Therefore, FE cannot be explained solely
      by an active FE mechanism involving the interaction of actin and myosin. Rather,
      these findings suggest a combination of underlying mechanisms, including a
      kinetic mechanism for active FE, contributions of a passive elastic element, and
      possibly an activatable passive component operating outside of actin-myosin cross
      bridging. Moreover, this transient analysis identifies that FE is not simply the
      opposite of FD, and its underlying mechanism(s) cannot simply be the opposite in
      nature. 

PMID- 24303107
TI  - Decreased stability of erythroblastic islands in integrin beta3-deficient mice.
AB  - Erythroblasts proliferate and differentiate in hematopoietic organs within
      erythroblastic islands (EI) composed of erythropoietic progenitor cells attached
      to a central macrophage. This cellular interaction crucially involves the
      erythroid intercellular adhesion molecule-4 (ICAM-4) and alphav integrin. Because
      integrins are biologically active as alpha/beta heterodimers, we asked whether
      beta3 could be a heterodimerization partner of alphav integrin in EIs. To this
      end we compared stress erythropoiesis driven by two different mechanisms, namely
      that of integrin beta3-deficient (beta3(-/-)) mice that exhibit impaired
      hemostasis due to platelet dysfunction with that of systemically erythropoietin
      overexpressing (tg6) mice. While compared to the respective wild type (wt)
      controls beta3(-/-) mice had much less erythropoietic stimulation than tg6 mice
      beta3(-/-) blood contained more erythrocytes of a lower maturity stage.
      Unexpectedly, membranes of peripheral erythrocytes from beta3(-/-) mice (but not
      those from either wt control or from tg6 mice) contained calnexin, a chaperone
      that is normally completely lost during terminal differentiation of reticulocytes
      prior to their release into the circulation. In contrast to erythropoietin
      overexpressing mice, the erythropoietic subpopulations representing
      orthochromatic erythroblasts and premature reticulocytes as well as the number of
      cells per EI were reduced in beta3(-/-) bone marrow. In conclusion, absence of
      integrin beta3 impairs adhesion of the latest erythroid developmental stage to
      the central macrophage of EIs resulting in preterm release of abnormally immature
      erythrocytes into the circulation. 

PMID- 24303108
TI  - Temperature affects maximum H-reflex amplitude but not homosynaptic
      postactivation depression.
AB  - This study aimed to determinate the effect of hyperthermia on transmission
      efficacy of the Ia-afferent spinal pathway. Recruitment curves of the Hoffman
      reflex (H-reflex) and compound motor potential (M-wave) along with homosynaptic
      postactivation depression (HPAD) recovery curves were obtained in 14 volunteers
      in two controlled ambient temperatures that resulted in significantly different
      core temperatures (CON, core temperature ~37.3 degrees C; and HOT, core
      temperature ~39.0 degrees C). Electromyographic responses were obtained from the
      soleus (SOL) and medial gastrocnemius (MG) muscles following electrical
      stimulation of the tibial nerve at varying intensities and paired pulse
      frequencies (0.07-10 Hz). Results showed that maximal amplitude of the H-reflex
      was reached for a similar intensity of stimulation in CON and HOT (both muscles P
      > 0.47), with a similar associated M-wave (both muscles P > 0.69) but was
      significantly decreased in HOT as compared to CON (all P < 0.05), whether
      expressed in absolute terms (-50% in SOL, -32% in MG) or when normalized to the
      maximum M-wave (-23% in SOL, -32% in MG). The HPAD recovery curve was not
      affected by the elevated core temperature (both muscles P > 0.23). Taken
      together, these results suggest that hyperthermia can alter neuromuscular
      transmission across the neuromuscular junction and/or muscle membrane as well as
      transmission efficacy of the Ia-afferent pathway, albeit the latter not via an
      increase in HPAD. 

PMID- 24303109
TI  - Pharmacological analysis of dopamine modulation in the Drosophila melanogaster
      larval heart.
AB  - Dopamine (DA) and other neurotransmitters affect nonneuronal tissues in insects
      by circulating in the hemolymph. In several organisms, DA has been shown to
      modulate distinct aspects of cardiac function but the signal transduction
      pathways that mediate dopaminergic effects on the heart are not well
      characterized. Here, we used a semiintact Drosophila melanogaster larva
      preparation and drugs targeting DA receptors and canonical second messenger
      pathways to identify signaling cascades that mediate the effect of DA on a
      myogenic heart. DA has a positive chronotropic effect that is mimicked by
      SKF38393 (type-1 DA receptor agonist) and quinpirole (type-2 DA receptor
      agonist). SCH23390 and spiperone (type-1 and type-2 DA receptor antagonists) are
      moderately effective at inhibiting DA's effect. An adenylate cyclase inhibitor
      (SQ,22536) is also effective at blocking the stimulatory effect of DA but the
      drug has its own dose-dependent effect. Activation of protein kinase C with a
      diacylglycerol analog has a stimulatory effect on heart rate (HR). These results
      suggest that (1) both DA receptor subtypes are expressed in third instar larva
      cardiac myocytes to increase HR in response to rising levels of DA in the
      hemolymph, and (2) canonical second messenger pathways modulate HR in D.
      melanogaster larvae. Having these disparate signaling cascades converge toward a
      common modulatory function appears redundant, but in the context of multiple
      cardioactive chemicals this redundancy is likely to increase the fidelity of
      signal transduction. 

PMID- 24303110
TI  - Modeling zero-lag synchronization of dorsal horn neurons during the traveling of
      electrical waves in the cat spinal cord.
AB  - The first electrophysiological evidence of the phenomenon of traveling electrical
      waves produced by populations of interneurons within the spinal cord was reported
      by our interdisciplinary research group. Two interesting observations derive from
      this study: first, the negative spontaneous cord dorsum potentials (CDPs) that
      are superimposed on the propagating sinusoidal electrical waves are not
      correlated with any scratching phase; second, these CDPs do not propagate along
      the lumbosacral spinal segments, but they appear almost simultaneously at
      different spinal segments. The aim of this study was to provide experimental data
      and a mathematical model to explain the simultaneous occurrence of traveling
      waves and the zero-lag synchronization of some CDPs. 

PMID- 24303111
TI  - Manipulation of arterial stiffness, wave reflections, and retrograde shear rate
      in the femoral artery using lower limb external compression.
AB  - Exposure of the arterial wall to retrograde shear acutely leads to endothelial
      dysfunction and chronically contributes to a proatherogenic vascular phenotype.
      Arterial stiffness and increased pressure from wave reflections are known
      arbiters of blood flow in the systemic circulation and each related to
      atherosclerosis. Using distal external compression of the calf to increase
      upstream retrograde shear in the superficial femoral artery (SFA), we examined
      the hypothesis that changes in retrograde shear are correlated with changes in
      SFA stiffness and pressure from wave reflections. For this purpose, a pneumatic
      cuff was applied to the calf and inflated to 0, 35, and 70 mmHg (5 min
      compression, randomized order, separated by 5 min) in 16 healthy young men (23 +/
      1 years of age). Doppler ultrasound and wave intensity analysis was used to
      measure SFA retrograde shear rate, reflected pressure wave intensity (negative
      area [NA]), elastic modulus (Ep), and a single-point pulse wave velocity (PWV)
      during acute cuff inflation. Cuff inflation resulted in stepwise increases in
      retrograde shear rate (P < 0.05 for main effect). There were also significant
      cuff pressure-dependent increases in NA, Ep, and PWV across conditions (P < 0.05
      for main effects). Change in NA, but not Ep or PWV, was associated with change in
      retrograde shear rate across conditions (P < 0.05). In conclusion, external
      compression of the calf increases retrograde shear, arterial stiffness, and
      pressure from wave reflection in the upstream SFA in a dose-dependent manner.
      Wave reflection intensity, but not arterial stiffness, is correlated with changes
      in peripheral retrograde shear with this hemodynamic manipulation. 

PMID- 24303112
TI  - Rat locomotor spinal circuits in vitro are activated by electrical stimulation
      with noisy waveforms sampled from human gait.
AB  - Noisy waveforms, sampled from an episode of fictive locomotion (FL) and delivered
      to a dorsal root (DR), are a novel electrical stimulating protocol demonstrated
      as the most effective for generating the locomotor rhythm in the rat isolated
      spinal cord. The present study explored if stimulating protocols constructed by
      sampling real human locomotion could be equally efficient to activate these
      locomotor networks in vitro. This approach may extend the range of usable
      stimulation protocols and provide a wide palette of noisy waveforms for this
      purpose. To this end, recorded electromyogram (EMG) from leg muscles of walking
      adult volunteers provided a protocol named ReaListim (Real Locomotion-induced
      stimulation) that applied to a single DR successfully activated FL. The smoothed
      kinematic profile of the same gait failed to do so like nonphasic noisy patterns
      derived from standing and isometric contraction. Power spectrum analysis showed
      distinctive low-frequency domains in ReaListim, along with the high-frequency
      background noise. The current study indicates that limb EMG signals (recorded
      during human locomotion) applied to DR of the rat spinal cord are more effective
      than EMG traces taken during standing or isometric contraction of the same
      muscles to activate locomotor networks. Finally, EMGs recorded during various
      human motor tasks demonstrated that noisy waves of the same periodicity as
      ReaListim, could efficiently activate the in vitro central pattern generator
      (CPG), regardless of the motor task from which they had been sampled. These data
      outline new strategies to optimize functional stimulation of spinal networks
      after injury. 

PMID- 24303113
TI  - Effects of high-frequency stimulation and doublets on dynamic contractions in rat
      soleus muscle exposed to normal and high extracellular [K(+)].
AB  - The development of maximal velocity and power in muscle depends on the ability to
      transmit action potentials (AP) at very high frequencies up to about 400 Hz.
      However, for every AP there is a small loss of K(+) to the interstitium, which
      during intense exercise, may build up to a point where excitability is reduced,
      thus limiting the intensity of further exercise. It is still unknown how the
      muscle responds to high-frequency stimulation when exposed to high [K(+)].
      Contractile parameters of the muscles (force [F], velocity [V], power [P], rate
      of force development [RFD], and work) were examined during dynamic contractions,
      performed in vitro using rat soleus muscles incubated in buffers containing 4 or
      8 mmol/L K(+) and stimulated with constant trains of tetanic or supratetanic
      frequency or with trains initiated by a high-frequency doublet, followed by
      tetanic or subtetanic trains. At 4 mmol/L K(+), an increase in frequency
      increased P max when using constant train stimulation. When stimulating with
      trains containing high-frequency doublets an increase in 120-msec work was seen,
      however, no increase in P max was observed. At 8 mmol/L K(+), no differences were
      seen for either P max or 120-msec work when increasing frequency or introducing
      doublets. In all experiments where the frequency was increased or doublets
      applied, an increase in RFD was seen in both normal and high [K(+)]. The results
      indicate that stimulation with supratetanic frequencies can improve dynamic
      muscle contractility, but improvements are attenuated when muscles are exposed to
      high extracellular [K(+)]. 

PMID- 24303114
TI  - Novel perspective: exercise training stimulus triggers the expression of the
      oncoprotein human double minute-2 in human skeletal muscle.
AB  - High expression levels of human double minute-2 (Hdm2) are often associated with
      increased risk of cancer. Hdm2 is well established as an oncoprotein exerting
      various tumorigenic effects. Conversely, the physiological functions of Hdm2 in
      nontumor cells and healthy tissues remain largely unknown. We previously
      demonstrated that exercise training stimulates expression of murine double minute
      2 (Mdm2), the murine analog of Hdm2, in rodent skeletal muscle and Mdm2 was
      required for exercise-induced muscle angiogenesis. Here we showed that exercise
      training stimulated the expression of Hdm2 protein in human skeletal muscle from
      +38% to +81%. This robust physiological response was observed in 60-70% of the
      subjects tested, in both young and senior populations. Similarly, exercise
      training stimulated the expression of platelet endothelial cell adhesion molecule
      1, an indicator of the level of muscle capillarization. Interestingly, a
      concomitant decrease in the tumor suppressor forkhead box O-1 (FoxO1)
      transcription factor levels did not occur with training although Mdm2/Hdm2 is
      known to inhibit FoxO1 expression in diseased skeletal muscle. This could suggest
      that Hdm2 has different targets when stimulated in a physiological context and
      that exercise training could be considered therapeutically in the context of
      cancer in combination with anti-Hdm2 drug therapies in order to preserve Hdm2
      physiological functions in healthy tissues. 

PMID- 24303115
TI  - Portable acoustic myography - a realistic noninvasive method for assessment of
      muscle activity and coordination in human subjects in most home and sports
      settings.
AB  - Muscle sound gives a local picture of muscles involved in a particular movement
      and is independent of electrical signals between nerve and muscle. Sound
      recording (acoustic myography) is a well-known noninvasive technique that has
      suffered from not being easily applicable, as well as not being able to register
      at sufficient sampling speed. With modern amplifiers and digital sound recording
      this has changed, and such assessment during movement outside a laboratory
      setting may be possible. Our aim was to develop a setup for muscle-sound
      assessment, which could be reliably applied in any local setting. A group of
      healthy subjects were assessed during standing, stair climbing, walking, and
      running. Piezoelectric microphones were applied to the skin using contact gel. A
      digital sound recorder enabled sampling speeds of around 96,000 Hz. Surface
      electromyography was measured in parallel as a comparison. The recorded signals
      were assessed and described in terms of signal frequency (Hz) and peak-to-peak
      amplitude (mV) using Chart software. Bioimpedance of the involved muscles was
      measured. Sound recording was shown to be an easy noninvasive method for
      assessment of muscle function during movement with the possibility of being
      applied in most clinical, sports, and home settings. Muscle sound gives a
      representation of the work of each muscle group during a complex movement,
      illustrated here by a step test, which revealed both concentric and eccentric
      activity. The method in the presented new setup has great potential for
      assessment of function in patients with musculoskeletal complaints in out-of
      clinic settings, as well as in sports. 

PMID- 24303116
TI  - Magnetic sensors using amorphous metal materials: detection of premature
      ventricular magnetic waves.
AB  - The detection of magnetic activity enables noncontact and noninvasive evaluation
      of electrical activity in humans. We review the detection of biomagnetic fields
      using amorphous metal wire-based magnetic sensors with the sensitivity of a pico
      Tesla (pT) level. We measured magnetic fields close to the thoracic wall in a
      healthy subject sitting on a chair. The magnetic sensor head was mounted
      perpendicularly against the thoracic wall. Simultaneous measurements with ECG
      showed that changes in the magnetic field were synchronized with the cardiac
      electric activity, and that the magnetic wave pattern changed reflecting
      electrical activity of the atrium and ventricle, despite a large variation.
      Furthermore, magnetic waves reflecting ventricular arrhythmia were recorded in
      the same healthy subject. These results suggest that this magnetic sensor
      technology is applicable to human physiology and pathophysiology research. We
      also discuss future applications of amorphous wire-based magnetic sensors as well
      as possible improvements. 

PMID- 24303117
TI  - Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae).
AB  - The aim of this study was to assess maximal heart rate (HR) and heart
      morphological changes in high altitude living "plateau pikas" and rats bred at
      2260 m. Rats and pikas were catheterized to measure HR (2260 m). After baseline
      measurements, 1 mg/kg of atropine (AT) and increasing doses of isoproterenol
      (IsoP) (0.1, 1, 10, and 100 MUg kg) were injected into animals. Right (RV) and
      left ventricles (LV) were removed to calculate Fulton's ratio (LV + septum (S) to
      RV weights) and to assess mRNA expression level of beta1- and beta2
      adrenoceptors, muscarinic m1 and m2 receptors, and vascular endothelial growth
      factor (VEGF). Resting HR was significantly lower in rats than in pikas and
      increased after AT injection only in rats. IsoP injection induced a significant
      increase in HR in rat for all doses, which was systematically greater than in
      pikas. In pikas HR was slightly increased only after the two highest
      concentrations of IsoP. Fulton's ratio was greater in rats compared with pikas
      but the LV + S adjusted for body weight was greater in pikas. Pikas showed lower
      beta1-adrenoceptors and muscarinic m2 receptors mRNA expression but larger VEGF
      mRNA expression than rats both in RV and LV. These results suggest that pikas
      have a lower maximal HR compared with rats certainly due to a decrease in beta
      adrenergic and muscarinic receptors mRNA expression. However, the LV hypertrophy
      probably led to an increase in stroke volume to maintain cardiac output in
      response to the cold and hypoxic environment. 

PMID- 24303118
TI  - Effect of H1- and H2-histamine receptor blockade on postexercise insulin
      sensitivity.
AB  - Following a bout of dynamic exercise, humans experience sustained postexercise
      vasodilatation in the previously exercised skeletal muscle which is mediated by
      activation of histamine (H1 and H2) receptors. Skeletal muscle glucose uptake is
      also enhanced following dynamic exercise. Our aim was to determine if blunting
      the vasodilatation during recovery from exercise would have an adverse effect on
      blood glucose regulation. Thus, we tested the hypothesis that insulin sensitivity
      following exercise would be reduced with H1- and H2-receptor blockade versus
      control (no blockade). We studied 20 healthy young subjects (12 exercise; eight
      nonexercise sham) on randomized control and H1- and H2-receptor blockade
      (fexofenadine and ranitidine) days. Following 60 min of upright cycling at 60%
      VO2 peak or nonexercise sham, subjects consumed an oral glucose tolerance
      beverage (1.0 g/kg). Blood glucose was determined from "arterialized" blood
      samples (heated hand vein). Postexercise whole-body insulin sensitivity (Matsuda
      insulin sensitivity index) was reduced 25% with H1- and H2-receptor blockade (P <
      0.05), whereas insulin sensitivity was not affected by histamine receptor
      blockade in the sham trials. These results indicate that insulin sensitivity
      following exercise is blunted by H1- and H2-receptor blockade and suggest that
      postexercise H1- and H2-receptor-mediated skeletal muscle vasodilatation benefits
      glucose regulation in healthy humans. 

PMID- 24303119
TI  - Acute stress and hippocampal output: exploring dorsal CA1 and subicular synaptic
      plasticity simultaneously in anesthetized rats.
AB  - The Cornu Ammonis-1 (CA1) subfield and subiculum (SUB) serve as major output
      structures of the hippocampal formation. Exploring forms of synaptic plasticity
      simultaneously within these two output regions may improve understanding of the
      dynamics of hippocampal circuitry and information transfer between hippocampal
      and cortical brain regions. Using a novel dual-channel electrophysiological
      preparation in urethane-anesthetized adult male Sprague-Dawley rats in vivo, we
      examined the effects of acute restraint stress (30 min) on short- and long-term
      forms of synaptic plasticity in both CA1 and SUB by stimulating the CA3 region.
      Paired-pulse facilitation was disrupted in SUB but not CA1 in the dual-channel
      experiments following exposure to acute stress. Disruptions in CA1 PPF were
      evident in subsequent single-channel experiments with a more anterior recording
      site. Acute stress disrupted long-term potentiation induced by high-frequency
      stimulation (10 bursts of 20 pulses at 200 Hz) in both CA1 and SUB. Low-frequency
      stimulation (900 pulses at 1 Hz) did not alter CA1 plasticity while a late
      developing potentiation was evident in SUB that was disrupted following exposure
      to acute stress. These findings highlight differences in the sensitivity to acute
      stress for distinct forms of synaptic plasticity within synapses in hippocampal
      output regions. The findings are discussed in relation to normal and aberrant
      forms of hippocampal-cortical information processing. 

PMID- 24303121
TI  - Left ventricular volume regulation in heart failure with preserved ejection
      fraction.
AB  - Ejection Fraction (EF) has attained the recognition as indicator of global
      ventricular performance. Remarkably, precise historical origins promoting the
      apparent importance of EF are scant. During early utilization EF has been
      declared a gold standard for the evaluation of the heart as a pump. In contrast,
      during the last two decades, clinicians have developed a measure of doubt in the
      universal applicability of EF. This reluctance lead to the introduction of a new
      and prevalent syndrome in which heart failure (HF) is diagnosed as having a
      preserved EF (pEF). We examine the existing criticism regarding EF, and describe
      a novel avenue to characterize ventricular function within the unifying framework
      of cardiac input-output volume regulation. This approach relates end-systolic
      volume (ESV) to end-diastolic volume (EDV), and derives for a subgroup matching
      pEF criteria a distinct pattern in the ESV-EDV domain. In patients with pEF (n =
      34), a clear difference (P < 0.0004) in the slope of the regression line for ESV
      versus EDV was demonstrated compared to control patients with EF < 50% (n = 29).
      These findings are confirmed by analysis of data presented in two independent
      publications. The volume regulation approach proposed employs primary end-point
      determinants (such as ESV and EDV) rather than derived quantities (e.g., the
      ratio EF or its differential parameter, that is, stroke volume) and confirms a
      distinct advantage over the classical Starling curve. Application of the ESV-EDV
      construct provides the basis and clarifies why some patients present as HFpEF,
      while others have reduced EF. 

PMID- 24303120
TI  - Molecular basis for impaired collateral artery growth in the spontaneously
      hypertensive rat: insight from microarray analysis.
AB  - Analysis of global gene expression in mesenteric control and collateral arteries
      was used to investigate potential molecules, pathways, and mechanisms responsible
      for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A
      fundamental difference was observed in overall gene expression pattern in SHR
      versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals
      were similar between rat strains. Ingenuity(r) Pathway Analysis (IPA) identified
      major differences between WKY and SHR in networks and biological functions
      related to cell growth and proliferation and gene expression. In SHR control
      arteries, several mechano-sensitive and redox-dependent transcription regulators
      were downregulated including JUN (-5.2*, P = 0.02), EGR1 (-4.1*, P = 0.01), and
      NFKB1 (-1.95*, P = 0.04). Predicted binding sites for NFKB and AP-1 were present
      in genes altered in WKY but not SHR collaterals. Immunostaining showed increased
      NFKB nuclear translocation in collateral arteries of WKY and apocynin-treated
      SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral
      growth in WKY, confirming a functional role of NFkB. Canonical pathways
      identified by IPA in WKY but not SHR included nitric oxide and renin-angiotensin
      system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation
      in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1
      with losartan prevented collateral luminal expansion in WKY. Together, these
      results suggest that collateral growth impairment results from an abnormality in
      a fundamental regulatory mechanism that occurs at a level between signal
      transduction and gene transcription and implicate redox-dependent modulation of
      mechano-sensitive transcription factors such as NFKB as a potential mechanism. 

PMID- 24303124
TI  - Functional subcellular distribution of beta1- and beta2-adrenergic receptors in
      rat ventricular cardiac myocytes.
AB  - beta-adrenergic stimulation is a key regulator of cardiac function. The
      localization of major cardiac adrenergic receptors (beta1 and beta2) has been
      investigated using biochemical and biophysical approaches and has led to
      contradictory results. This study investigates the functional subcellular
      localization of beta1- and beta2-adrenergic receptors in rat ventricular myocytes
      using a physiological approach. Ventricular myocytes were isolated from the
      hearts of rat and detubulated using formamide. Physiological cardiac function was
      measured as Ca(2+) transient using Fura-2-AM and cell shortening. Selective
      activation of beta1- and beta2-adrenergic receptors was induced with
      isoproterenol (0.1 MUmol/L) and ICI-118,551 (0.1 MUmol/L); and with salbutamol
      (10 MUmol/L) and atenolol (1 MUmol/L), respectively. beta1- and beta2-adrenergic
      stimulations induced a significant increase in Ca(2+) transient amplitude and
      cell shortening in intact rat ventricular myocytes (i.e., surface sarcolemma and
      t-tubules) and in detubulated cells (depleted from t-tubules, surface sarcolemma
      only). Both beta1- and beta2-adrenergic receptors stimulation caused a greater
      effect on Ca(2+) transient and cell shortening in detubulated myocytes than in
      control myocytes. Quantitative analysis indicates that beta1-adrenergic
      stimulation is ~3 times more effective at surface sarcolemma compared to t
      tubules, whereas beta2- adrenergic stimulation occurs almost exclusively at
      surface sarcolemma (~100 times more effective). These physiological data
      demonstrate that in rat ventricular myocytes, beta1-adrenergic receptors are
      functionally present at surface sarcolemma and t-tubules, while beta2-adrenergic
      receptors stimulation occurs only at surface sarcolemma of cardiac cells. 

PMID- 24303126
TI  - Effects of prior acute exercise on circulating cytokine concentration responses
      to a high-fat meal.
AB  - High-fat meal consumption alters the circulating cytokine profile and contributes
      to cardiometabolic diseases. A prior bout of exercise can ameliorate the
      triglyceride response to a high-fat meal, but the interactive effects of exercise
      and high-fat meals on cytokines that mediate cardiometabolic risk are not fully
      understood. We investigated the effects of prior exercise on the responses of
      circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8,
      leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF),
      and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy
      men were studied before and 4 h after ingestion of a high-fat meal either with or
      without ~50 min of endurance exercise at 70% of VO2 max on the preceding day. In
      response to the high-fat meal, lower leptin and higher VEGF, bFGF, IL-6, and IL-8
      concentrations were evident (P < 0.05 for all). There was no effect of the high
      fat meal on PlGF, TNF-alpha, or RBP4 concentrations. We found lower leptin
      concentrations with prior exercise (P < 0.05) and interactive effects of prior
      exercise and the high-fat meal on sFlt-1 (P < 0.05). The high-fat meal increased
      IL-6 by 59% without prior exercise and 218% with prior exercise (P < 0.05). In
      conclusion, a prior bout of endurance exercise does not affect all high-fat meal
      induced changes in circulating cytokines, but does affect fasting or postprandial
      concentrations of IL-6, leptin, and sFlt-1. These data may reflect a salutary
      effect of prior exercise on metabolic responses to a high-fat meal. 

PMID- 24303125
TI  - Comparative differential proteomic profiles of nonfailing and failing hearts
      after in vivo thoracic aortic constriction in mice overexpressing FKBP12.6.
AB  - Chronic pressure overload (PO) induces pathological left ventricular hypertrophy
      (LVH) leading to congestive heart failure (HF). Overexpression of FKBP12.6 (FK506
      binding protein [K]) in mice should prevent Ca2+-leak during diastole and may
      improve overall cardiac function. In order to decipher molecular mechanisms
      involved in thoracic aortic constriction (TAC)-induced cardiac remodeling and the
      influence of gender and genotype, we performed a proteomic analysis using two
      dimensional differential in-gel electrophoresis (2D-DIGE), mass spectrometry, and
      bioinformatics techniques to identify alterations in characteristic biological
      networks. Wild-type (W) and K mice of both genders underwent TAC. Thirty days
      post-TAC, the altered cardiac remodeling was accompanied with systolic and
      diastolic dysfunction in all experimental groups. A gender difference in
      inflammatory protein expression (fibrinogen, alpha-1-antitrypsin isoforms) and in
      calreticulin occurred (males > females). Detoxification enzymes and cytoskeletal
      proteins were noticeably increased in K mice. Both non- and congestive failing
      mouse heart exhibited down- and upregulation of proteins related to mitochondrial
      function and purine metabolism, respectively. HF was characterized by a decrease
      in enzymes related to iron homeostasis, and altered mitochondrial protein
      expression related to fatty acid metabolism, glycolysis, and redox balance.
      Moreover, two distinct differential protein profiles characterized TAC-induced
      pathological LVH and congestive HF in all TAC mice. FKBP12.6 overexpression did
      not influence TAC-induced deleterious effects. Huntingtin was revealed as a
      potential mediator for HF. A broad dysregulation of signaling proteins associated
      with congestive HF suggested that different sets of proteins could be selected as
      useful biomarkers for HF progression and might predict outcome in PO-induced
      pathological LVH. 

PMID- 24303127
TI  - Tulobuterol inhibits rhinovirus infection in primary cultures of human tracheal
      epithelial cells.
AB  - A transdermal patch preparation of the beta2 agonist tulobuterol has been
      designed to yield sustained beta2 agonistic effects and has been used as a long
      acting beta2 agonist (LABA) in Japan. LABAs reduce the frequency of exacerbations
      of chronic obstructive pulmonary disease and bronchial asthma. However,
      inhibitory effects of LABAs on the replication of rhinovirus (RV), the major
      cause of exacerbations, have not been demonstrated. To examine the effects of
      tulobuterol on RV replication and on the production of the replication-induced
      pro-inflammatory cytokines, human tracheal epithelial cells were infected with a
      major group RV, type 14 rhinovirus (RV14). Tulobuterol reduced the RV14 titers
      and RNA levels; the concentrations of cytokines, including interleukin (IL)
      1beta, IL-6, and IL-8, in the supernatants; and susceptibility to RV14 infection.
      Tulobuterol reduced the expression of intercellular adhesion molecule-1 (ICAM-1),
      the receptor for RV14, and the number of acidic endosomes in the cells in which
      RV14 RNA enters the cytoplasm. Tulobuterol inhibited the activation of nuclear
      factor kappa B (NF-kappaB) proteins in nuclear extracts. A selective beta2
      adrenergic receptor antagonist, ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)
      3-isopropylaminobutan-2-ol], reversed the inhibitory effects of tulobuterol on
      the RV14 titers and RNA levels, the susceptibility to RV14 infection, cytokine
      production, and ICAM-1 expression. Tulobuterol may inhibit RV replication by
      reducing ICAM-1 expression and acidic endosomes and modulate airway inflammation
      during RV replication. 

PMID- 24303128
TI  - The quest for load-independent left ventricular chamber properties: Exploring the
      normalized pressure phase plane.
AB  - The pressure phase plane (PPP), defined by dP(t)/dt versus P(t) coordinates has
      revealed novel physiologic relationships not readily obtainable from
      conventional, time domain analysis of left ventricular pressure (LVP). We extend
      the methodology by introducing the normalized pressure phase plane (nPPP),
      defined by 0 <= P <= 1 and -1 <= dP/dt <= +1. Normalization eliminates load
      dependent effects facilitating comparison of conserved features of nPPP loops.
      Hence, insight into load-invariant systolic and diastolic chamber properties and
      their coupling to load can be obtained. To demonstrate utility, high-fidelity
      P(t) data from 14 subjects (4234 beats) was analyzed. PNR, the nPPP
      (dimensionless) pressure, where -dP/dtpeak occurs, was 0.61 and had limited
      variance (7%). The relative load independence of PNR was corroborated by
      comparison of PPP and nPPP features of normal sinus rhythm (NSR) and (ejecting
      and nonejecting) premature ventricular contraction (PVC) beats. PVCs had lower
      P(t)max and lower peak negative and positive dP(t)/dt values versus NSR beats. In
      the nPPP, +dP/dtpeak occurred at higher (dimensionless) P in PVC beats than in
      regular beats (0.44 in NSR vs. 0.48 in PVC). However, PNR for PVC versus NSR
      remained unaltered (PNR = 0.64; P > 0.05). Possible mechanistic explanation
      includes a (near) load-independent (constant) ratio of maximum cross-bridge
      uncoupling rate to instantaneous wall stress. Hence, nPPP analysis reveals LV
      properties obscured by load and by conventional temporal P(t) and dP(t)/dt
      analysis. nPPP identifies chamber properties deserving molecular and cellular
      physiologic explanation. 

PMID- 24303129
TI  - Identification and characterization of novel Kirrel isoform during myogenesis.
AB  - Somatic cell fusion is an essential component of skeletal muscle development and
      growth and repair from injury. Additional cell types such as trophoblasts and
      osteoclasts also require somatic cell fusion events to perform their
      physiological functions. Currently we have rudimentary knowledge on molecular
      mechanisms regulating somatic cell fusion events in mammals. We therefore
      investigated during in vitro murine myogenesis a mammalian homolog, Kirrel, of
      the Drosophila Melanogaster genes Roughest (Rst) and Kin of Irre (Kirre) which
      regulate somatic muscle cell fusion during embryonic development. Our results
      demonstrate the presence of a novel murine Kirrel isoform containing a truncated
      cytoplasmic domain which we term Kirrel B. Protein expression levels of Kirrel B
      are inverse to the occurrence of cell fusion events during in vitro myogenesis
      which is in stark contrast to the expression profile of Rst and Kirre during
      myogenesis in Drosophila. Furthermore, chemical inhibition of cell fusion
      confirmed the inverse expression pattern of Kirrel B protein levels in relation
      to cell fusion events. The discovery of a novel Kirrel B protein isoform during
      myogenesis highlights the need for more thorough investigation of the
      similarities and potential differences between fly and mammals with regards to
      the muscle cell fusion process. 

PMID- 24303130
TI  - Effect of simvastatin in the autonomic system is dependent on the increased
      gain/sensitivity of the baroreceptors.
AB  - A number of mechanisms have been proposed to explain the pleiotropic effect of
      statin therapy to reduce sympathetic outflow in cardiovascular disease. We tested
      the hypothesis that statin treatment could improve baroreflex gain-sensitivity
      triggered by morphological adaptations in the mechanoreceptor site, thus reducing
      sympathetic activity, regardless of arterial pressure (AP) level reduction. Male
      spontaneously hypertensive rats (SHR) were divided into control (SHR, n = 8) and
      SHR-simvastatin (5 mg/kg/day, for 7 days) (SHR-S, n = 8). After treatment, AP,
      baroreflex sensitivity (BRS) in response to AP-induced changes, aortic depressor
      nerve activity, and spectral analyses of pulse interval (PI) and AP variabilities
      were performed. Internal and external carotids were prepared for
      morphoquantitative evaluation. Although AP was similar between groups,
      sympathetic modulation, represented by the low frequency band of PI (SHR: 6.84 +/
      3.19 vs. SHR-S: 2.41 +/- 0.96 msec(2)) and from systolic AP variability (SHR:
      3.95 +/- 0.36 vs. SHR-S: 2.86 +/- 0.18 mmHg(2)), were reduced in treated animals.
      In parallel, simvastatin induced an increase of 26% and 21% in the number of
      elastic lamellae as well as a decrease of 9% and 25% in the carotid thickness in
      both, external and internal carotid, respectively. Moreover, improved
      baroreceptor function (SHR: 0.78 +/- 0.03 vs. SHR-S: 1.06 +/- 0.04% mv/mmHg) was
      observed in addition to a 115% increase in aortic depressor nerve activity in SHR
      S rats. Therefore, our data suggest that the reduction of sympathetic outflow in
      hypertension by simvastatin treatment may be triggered by structural changes in
      the carotid arteries and increased BRS in response to an improvement of the
      baroreceptors discharge and consequently of the afferent pathway of the
      baroreflex arch.

PMID- 24303131
TI  - Mechanistic analysis for time-dependent effects of cinacalcet on serum calcium,
      phosphorus, and parathyroid hormone levels in 5/6 nephrectomized rats.
AB  - This study investigates the time-dependent effects of cinacalcet on serum
      calcium, phosphorus, and parathyroid hormone (PTH) levels in 5/6 nephrectomized
      (NX) rats with experimental chronic renal insufficiency. In this study, 5/6 NX
      male, Sprague-Dawley rats were treated with vehicle or cinacalcet (10 mg/kg,
      oral, 1* daily). On Day 0 (before treatment), Day 12 and 13 after treatment (to
      approximate the clinical practice), and also at 0, 1, 4, 8, 16, and 24 hours
      after the last dosing, blood was collected for analysis. After 12 or 13 days of
      cinacalcet treatment, modest changes were observed in serum Ca and phosphorus
      (Pi), while PTH decreased by >45% to Sham levels (152 +/- 15 pg/mL). Detailed
      mapping found that cinacalcet caused a significant time-dependent decrease in
      serum Ca following dosing, reaching a lowest point at 8 hours (decrease by 20% to
      8.43 +/- 0.37 mg/dL), and then returning to normal at 24 hours. Cinacalcet also
      caused a significant increase in serum Pi levels (by 18%). To investigate the
      potential mechanism of action, a broad approach was taken by testing cinacalcet
      in a panel of 77 protein-binding assays. Cinacalcet interacted with several
      channels, transporters, and neurotransmitter receptors, some of which are
      involved in brain and heart, and may impact Ca homeostasis. Cinacalcet dose
      dependently increased brain natriuretic peptide (BNP) mRNA expression by 48% in
      cardiomyocytes, but had no significant effects on left ventricular hypertrophy
      and cardiac function. The results suggest that cinacalcet's hypocalcemic effect
      may be due to its nonspecific interaction with other receptors in brain and
      heart. 

PMID- 24303132
TI  - Endocrine rhythms in the brown bear (Ursus arctos): Evidence supporting selection
      for decreased pineal gland size.
AB  - Many temperate zone animals adapt to seasonal changes by altering their
      physiology. This is mediated in large part by endocrine signals that encode day
      length and regulate energy balance and metabolism. The objectives of this study
      were to determine if the daily patterns of two important hormones, melatonin and
      cortisol, varied with day length in captive brown bears (Ursus arctos) under
      anesthetized and nonanesthetized conditions during the active (March-October) and
      hibernation periods. Melatonin concentrations varied with time of day and season
      in nonanesthetized female bears despite exceedingly low nocturnal concentrations
      (1-4 pg/mL) in the active season. In contrast, melatonin concentrations during
      hibernation were 7.5-fold greater than those during the summer in anesthetized
      male bears. Functional assessment of the pineal gland revealed a slight but
      significant reduction in melatonin following nocturnal light application during
      hibernation, but no response to beta-adrenergic stimulation was detected in
      either season. Examination of pineal size in two bear species bears combined with
      a phylogenetically corrected analysis of pineal glands in 47 other species
      revealed a strong relationship to brain size. However, pineal gland size of both
      bear species deviated significantly from the expected pattern. Robust daily
      plasma cortisol rhythms were observed during the active season but not during
      hibernation. Cortisol was potently suppressed following injection with a
      synthetic glucocorticoid. The results suggest that melatonin and cortisol both
      retain their ability to reflect seasonal changes in day length in brown bears.
      The exceptionally small pineal gland in bears may be the result of direct or
      indirect selection. 

PMID- 24303133
TI  - Extraction of basic movement from whole-body movement, based on gait variability.
AB  - The aim of this study was to quantify the step-to-step variability (SSV) in speed
      variant and speed-invariant movement components of the whole-body gait pattern
      during running. These separate aspects of variability can be used to gain insight
      into the neuromuscular control strategies that are engaged during running. Ten
      healthy, physically active, male recreational athletes performed five treadmill
      running trials at five different speeds (range: 1.3-4.9 m/sec). The whole-body
      movement was separated into principal movements (PM) using a principal component
      analysis. The PMs were split into two groups: a speed-variant group, where the
      range of motion (amplitude of PMs) changed with running speed; and a speed
      invariant group, where the range of motion was constant across various speeds.
      The step-to-step variability (SSV) of the two groups was then quantified. The
      absolute SSV was the summed variability across all gait cycles, whereas the
      relative SSV was the summed variability divided by the magnitude of the movement.
      The absolute SSV of the speed-variant movements increased with running speed. By
      contrast, the relative SSV of the speed-variant group (as normalized to the PM
      amplitude) decreased asymptotically toward a minimal level as running speed
      increased. Both the absolute and relative SSV of the speed-invariant movements
      revealed a minimum at 3.1 m/sec. The whole-body gait pattern during running can
      be subdivided into speed-variant and speed-invariant movements. An interpretation
      of the SSV based on minimal intervention theory suggests that speed-variant
      movements are more tightly controlled, as evidenced by a lower degree of
      variability compared to the speed-invariant movements. 

PMID- 24303135
TI  - Reinvestigation of the relationship between the amplitude of the first heart
      sound to cardiac dynamics.
AB  - The relationships between the amplitude of the first heart sound (S1) and the
      rising rate of left ventricular pressure (LVP) concluded in previous studies were
      not consistent. Some researchers believed the relationship was positively linear;
      others stated the relationship was only positively correlated. To further
      investigate this relationship, this study simultaneously sampled the external
      phonocardiogram, electrocardiogram, and intracardiac pressure in the left
      ventricle in three anesthetized dogs, while invoking wide hemodynamic changes
      using various doses of epinephrine. The relationship between the maximum
      amplitude of S1 and the maximum rising rate of LVP and the relationship between
      the amplitude of dominant peaks/valleys and the corresponding rising rate of LVP
      were examined by linear, quadratic, cubic, and exponential models. The results
      showed that the relationships are best fit by nonlinear exponential models. 

PMID- 24303134
TI  - Acceleration dependence and task-specific modulation of short- and medium-latency
      reflexes in the ankle extensors.
AB  - Involuntary responses to muscle stretch are often composed of a short-latency
      reflex (SLR) and more variable responses at longer latencies such as the medium
      latency (MLR) and long-latency stretch reflex (LLR). Although longer latency
      reflexes are enhanced in the upper limb during stabilization of external loads,
      it remains unknown if they have a similar role in the lower limb. This
      uncertainty results in part from the inconsistency with which longer latency
      reflexes have been observed in the lower limb. A review of the literature
      suggests that studies that only observe SLRs have used perturbations with large
      accelerations, possibly causing a synchronization of motoneuron refractory
      periods or an activation of force-dependent inhibition. We therefore hypothesized
      that the amplitude of longer latency reflexes would vary with perturbation
      acceleration. We further hypothesized that if longer latency reflexes were
      elicited, they would increase in amplitude during control of an unstable load, as
      has been observed in the upper limb. These hypotheses were tested at the ankle
      while subjects performed a torque or position control task. SLR and MLR reflex
      components were elicited by ankle flexion perturbations with a fixed peak
      velocity and variable acceleration. Both reflex components initially scaled with
      acceleration, however, while the SLR continued to increase at high accelerations,
      the MLR weakened. At accelerations that reliably elicited MLRs, both the SLR and
      MLR were reduced during control of the unstable load. These findings clarify the
      conditions required to elicit MLRs in the ankle extensors and provide additional
      evidence that rapid feedback pathways are downregulated when stability is
      compromised in the lower limb. 

PMID- 24303136
TI  - Adrenocortical control in the neonatal rat: ACTH- and cAMP-independent
      corticosterone production during hypoxia.
AB  - We have previously demonstrated that the neonatal corticosterone response to
      acute hypoxia shifts from ACTH independence to ACTH dependence between postnatal
      days two (PD2) and eight (PD8). Cyclic AMP (cAMP) is the obligatory intracellular
      second messenger of ACTH action, and we hypothesized that corticosterone
      production in neonatal rats shifts from a cAMP-independent mechanism to cAMP
      dependent mechanism between PD2 and PD8. Plasma ACTH and corticosterone and
      adrenal cAMP and cGMP responses to acute severe hypoxia (8% O2 for 5, 10, 20, 30,
      and 180 min) were measured in neonatal rats at PD2, PD8, and PD15. Plasma ACTH
      and corticosterone were measured by radioimmunoassay, and adrenal cAMP and cGMP
      were measured by ELISA. Plasma corticosterone-binding globulin (CBG) was measured
      in normoxic pups by ELISA. The largest corticosterone response was observed in
      PD2 pups, despite only a small increase in plasma ACTH that was not sustained.
      The PD2 ACTH-independent increase in corticosterone occurred with no change in
      adrenal cAMP or cGMP content. Plasma CBG concentration was lowest in PD2 pups.
      Large corticosterone responses were measured during the first 30 min of hypoxia.
      Differences in corticosterone responses between PD2 and PD8 pups cannot be
      attributed to changes in plasma protein binding capacity, and the PD2
      corticosterone response is consistent with a nongenomic mechanism of action. We
      conclude that the sustained corticosterone response to hypoxia in PD2 pups occurs
      with small and transient ACTH responses and independently of increases in adrenal
      cAMP or cGMP. 

PMID- 24303137
TI  - Coupling blood flow and neural function in the retina: a model for homeostatic
      responses to ocular perfusion pressure challenge.
AB  - Retinal function is known to be more resistant than blood flow to acute reduction
      of ocular perfusion pressure (OPP). To understand the mechanisms underlying the
      disconnect between blood flow and neural function, a mathematical model is
      developed in this study, which proposes that increased oxygen extraction ratio
      compensates for relative ischemia to sustain retinal function. In addition, the
      model incorporates a term to account for a pressure-related mechanical stress on
      neurons when OPP reduction is achieved by intraocular pressure (IOP) elevation.
      We show that this model, combining ocular blood flow, oxygen extraction ratio,
      and IOP mechanical stress on neurons, accounts for retinal function over a wide
      range of OPP manipulations. The robustness of the model is tested against
      experimental data where ocular blood flow, oxygen tension, and retinal function
      were simultaneously measured during acute OPP manipulation. The model provides a
      basis for understanding the retinal hemodynamic responses to short-term OPP
      challenge. 

PMID- 24303138
TI  - Focal axonal swellings and associated ultrastructural changes attenuate
      conduction velocity in central nervous system axons: a computer modeling study.
AB  - The constancy of action potential conduction in the central nervous system (CNS)
      relies on uniform axon diameter coupled with fidelity of the overlying myelin
      providing high-resistance, low capacitance insulation. Whereas the effects of
      demyelination on conduction have been extensively studied/modeled, equivalent
      studies on the repercussions for conduction of axon swelling, a common early
      pathological feature of (potentially reversible) axonal injury, are lacking. The
      recent description of experimentally acquired morphological and electrical
      properties of small CNS axons and oligodendrocytes prompted us to incorporate
      these data into a computer model, with the aim of simulating the effects of focal
      axon swelling on action potential conduction. A single swelling on an otherwise
      intact axon, as occurs in optic nerve axons of Cnp1 null mice caused a small
      decrease in conduction velocity. The presence of single swellings on multiple
      contiguous internodal regions (INR), as likely occurs in advanced disease, caused
      qualitatively similar results, except the dimensions of the swellings required to
      produce equivalent attenuation of conduction were significantly decreased. Our
      simulations of the consequences of metabolic insult to axons, namely, the
      appearance of multiple swollen regions, accompanied by perturbation of overlying
      myelin and increased axolemmal permeability, contained within a single INR,
      revealed that conduction block occurred when the dimensions of the simulated
      swellings were within the limits of those measured experimentally, suggesting
      that multiple swellings on a single axon could contribute to axonal dysfunction,
      and that increased axolemmal permeability is the decisive factor that promotes
      conduction block. 

PMID- 24303139
TI  - Insulin signaling in skeletal muscle of HIV-infected patients in response to
      endurance and strength training.
AB  - Human immunodeficiency virus (HIV)-infected patients with lipodystrophy have
      decreased insulin-stimulated glucose uptake. Both endurance and resistance
      training improve insulin-stimulated glucose uptake in skeletal muscle of HIV
      infected patients, but the mechanisms are unknown. This study aims to identify
      the molecular pathways involved in the beneficial effects of training on insulin
      stimulated glucose uptake in skeletal muscle of HIV-infected patients. Eighteen
      sedentary male HIV-infected patients underwent a 16 week supervised training
      intervention, either resistance or strength training. Euglycemic-hyperinsulinemic
      clamps with muscle biopsies were performed before and after the training
      interventions. Fifteen age- and body mass index (BMI)-matched HIV-negative men
      served as a sedentary baseline group. Phosphorylation and total protein
      expression of insulin signaling molecules as well as glycogen synthase (GS)
      activity were analyzed in skeletal muscle biopsies in relation to insulin
      stimulation before and after training. HIV-infected patients had reduced basal
      and insulin-stimulated GS activity (%fractional velocity, [FV]) as well as
      impaired insulin-stimulated Akt(thr308) phosphorylation. Despite improving
      insulin-stimulated glucose uptake, neither endurance nor strength training
      changed the phosphorylation status of insulin signaling proteins or affected GS
      activity. However; endurance training markedly increased the total Akt protein
      expression, and both training modalities increased hexokinase II (HKII) protein.
      HIV-infected patients with lipodystrophy have decreased insulin-stimulated
      glucose uptake in skeletal muscle and defects in insulin-stimulated
      phosphorylation of Akt(thr308). Endurance and strength training increase insulin
      stimulated glucose uptake in these patients, and the muscular training adaptation
      is associated with improved capacity for phosphorylation of glucose by HKII,
      rather than changes in markers of insulin signaling to glucose uptake or glycogen
      synthesis. 

PMID- 24303140
TI  - Depolarization-induced depression of inhibitory transmission in cerebellar
      Purkinje cells.
AB  - Several forms of depolarization-induced plasticity in inhibitory transmission
      have been reported to occur in cerebellar Purkinje cells (PCs), namely
      depolarization-induced suppression of inhibition (DSI), depolarization-induced
      potentiation of inhibition (DPI), and rebound potentiation (RP). Here, we
      describe another form of synaptic plasticity for gamma-amino butyric acid
      (GABA)ergic transmission in PCs. Immediately following depolarization trains in a
      PC, evoked inhibitory postsynaptic currents (eIPSCs) changed their direction from
      outward to inward currents under a recording condition in which eIPSCs were
      elicited as an outward current. Subsequently, the eIPSC amplitude remained
      depressed (depolarization-induced depression of inhibition [DDI]) for more than
      20 min under the blockade of cannabinoid and N-methyl-D-aspartic acid (NMDA)
      receptor-mediated DSI and DPI, respectively. This DDI was completely abolished by
      intracellular infusion of the fast Ca(2+)-chelating agent BAPTA and by inhibition
      of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Furthermore, DDI was
      strongly suppressed by calcium-activated chloride channel (CaCC) blockers, while
      an inhibitor of cation-chloride cotransporters (CCCs) partially blocked DDI
      during the early phase. Exogenous GABA-induced inhibition of spontaneous spike
      activity was attenuated in ~50% of the PCs by climbing fiber stimulation-induced
      depolarization. These results suggest that activation of both CaCCs and CCCs was
      necessary for alteration of [Cl(-)]i after activation of CaMKII following
      elevation of [Ca(2+)]i in PCs. DDI may provide another mechanism for regulation
      of inhibitory inputs to PCs within the neuronal networks of the cerebellar
      cortex. 

PMID- 24303141
TI  - Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT
      4 deletion.
AB  - To investigate the importance of the glucose transporter GLUT-4 for muscle
      glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4
      expression approximately 30-60% of normal (CON) and approximately 5-10% of normal
      (KO) were generated using the Cre/Lox system and compared with wild-type (WT)
      mice during approximately 40 min of treadmill running (KO: 37.7 +/- 1.3 min; WT:
      40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an
      overall increase in muscle glucose uptake. More specifically, glucose uptake was
      increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius
      of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake
      in all muscles was completely abolished in KO mice. Muscle glucose uptake
      increased during exercise in both red and white quadriceps of WT mice, while the
      small increases in CON mice were not statistically significant. In KO mice, there
      was no change at all in quadriceps muscle glucose uptake. No differences in
      muscle glycogen use during exercise were observed between any of the groups.
      However, there was a significant increase in plasma glucose levels after exercise
      in KO mice. The results of this study demonstrated that a reduction in skeletal
      muscle GLUT-4 expression to approximately 10% of normal levels completely
      abolished the exercise-induced increase in muscle glucose uptake. 

PMID- 24303142
TI  - Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and
      performance during 15-km time trial cycling in severe normobaric hypoxia: the
      role of cerebral O2 delivery.
AB  - During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral
      vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A
      reduction in CBF would impair cerebral O2 delivery and potentially account for
      reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal
      Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced
      reduction in CBF during heavy exercise, thus improving exercise performance. We
      measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal
      cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation),
      cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10
      healthy men (age 27 +/- 7 years; VO2max 63.3 +/- 6.6 mL/kg/min; mean +/- SD)
      during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 =
      0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and
      lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping
      elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions
      (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb
      (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2
      during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping
      restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have
      a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097).
      However, post hoc analysis revealed no effect of CO2 clamping on TT performance
      either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm
      that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral
      oxygenation are unlikely to be the cause of the reduced endurance exercise
      performance in hypoxia. 

PMID- 24303143
TI  - Regeneration of injured skeletal muscle in heat shock transcription factor 1-null
      mice.
AB  - The purpose of this study was to investigate a role of heat shock transcription
      factor 1 (HSF1)-mediated stress response during regeneration of injured soleus
      muscle by using HSF1-null mice. Cardiotoxin (CTX) was injected into the left
      muscle of male HSF1-null and wild-type mice under anesthesia with intraperitoneal
      injection of pentobarbital sodium. Injection of physiological saline was also
      performed into the right muscle. Soleus muscles were dissected bilaterally 2 and
      4 weeks after the injection. The relative weight and fiber cross-sectional area
      in CTX-injected muscles of HSF1-null, not of wild-type, mice were less than
      controls with injection of physiological saline 4 weeks after the injury,
      indicating a slower regeneration. Injury-related increase of Pax7-positive muscle
      satellite cells in HSF1-null mice was inhibited versus wild-type mice. HSF1
      deficiency generally caused decreases in the basal expression levels of heat
      shock proteins (HSPs). But the mRNA expression levels of HSP25 and HSP90alpha in
      HSF1-null mice were enhanced in response to CTX-injection, compared with wild
      type mice. Significant up-regulations of proinflammatory cytokines, such as
      interleukin (IL) -6, IL-1beta, and tumor necrosis factor mRNAs, with greater
      magnitude than in wild-type mice were observed in HSF1-deficient mouse muscle.
      HSF1 and/or HSF1-mediated stress response may play a key role in the regenerating
      process of injured skeletal muscle. HSF1 deficiency may depress the regenerating
      process of injured skeletal muscle via the partial depression of increase in Pax7
      positive satellite cells. HSF1-deficiency-associated partial depression of
      skeletal muscle regeneration might also be attributed to up-regulation of
      proinflammatory cytokines. 

PMID- 24303144
TI  - Assessment of the ergogenic effect of caffeine supplementation on mood,
      anticipation timing, and muscular strength in older adults.
AB  - The effect of caffeine to promote improvements in mood, cognition, and exercise
      performance has been well established in young and athletic adults. However,
      little is known about whether such nutritional ergogenic aids are effective in
      enhancing psychological well-being, physiological or cognitive performance in
      older adults. This study assesses the ergogenic effect of caffeine on mood,
      perceptual-motor coupling, and muscular strength in an older human population.
      Following a familiarization session, 12 apparently healthy volunteers (nine
      females and three males; 69 +/- 6 years) completed two laboratory visits. "Pre
      ingestion" trials of mood state Brunel Mood State Inventory (BRUMS) and
      coincidence anticipation performance (Bassin anticipation timer) at slow (3 mph)
      and fast (8 mph) stimulus speeds were completed on both visits. Using a
      randomized, double-blind, cross-over design, participants consumed either
      caffeine (3 mg/kg body mass) or a placebo. Sixty minutes postingestion
      participants repeated the trials before completing a set of 10 consecutive
      repetitions of maximal knee extension using isokinetic dynamometry. Rating of
      perceived exertion (RPE) was assessed following the fifth and final repetition.
      Caffeine ingestion significantly improved mood state scores for vigor by 17% (P =
      0.009) and reduced absolute error by 35% (P = 0.045) during coincidence
      anticipation assessment at 8 mph compared to placebo. There were no other
      significant effects. Caffeine ingestion failed to augment maximal voluntary
      contraction of the knee extensors and RPE did not prove to be significantly
      different to from placebo (P > 0.33 in each case). Acute caffeine ingestion may
      not be an effective ergogenic aid for improving muscular strength in older adults
      but could possibly be used as a nutrition supplement for enhancing mood and
      improving cognitive performance in daily living tasks where interceptive timing
      skills are required. 

PMID- 24303146
TI  - Unique growth pattern of human mammary epithelial cells induced by polymeric
      nanoparticles.
AB  - Due to their unique properties, engineered nanoparticles (NPs) have found broad
      use in industry, technology, and medicine, including as a vehicle for drug
      delivery. However, the understanding of NPs' interaction with different types of
      mammalian cells lags significantly behind their increasing adoption in drug
      delivery. In this study, we show unique responses of human epithelial breast
      cells when exposed to polymeric Eudragit(r) RS NPs (ENPs) for 1-3 days. Cells
      displayed dose-dependent increases in metabolic activity and growth, but lower
      proliferation rates, than control cells, as evidenced in tetrazolium salt (WST-1)
      and 5-bromo-2'-deoxyuridine (BrdU) assays, respectively. Those effects did not
      affect cell death or mitochondrial fragmentation. We attribute the increase in
      metabolic activity and growth of cells culture with ENPs to three factors: (1)
      high affinity of proteins present in the serum for ENPs, (2) adhesion of ENPs to
      cells, and (3) activation of proliferation and growth pathways. The proteins and
      genes responsible for stimulating cell adhesion and growth were identified by
      mass spectrometry and Microarray analyses. We demonstrate a novel property of
      ENPs, which act to increase cell metabolic activity and growth and organize
      epithelial cells in the epithelium as determined by Microarray analysis. 

PMID- 24303147
TI  - Influence of different positions on hemodynamics derived from noninvasive
      transcutaneous Doppler ultrasound.
AB  - A proper alignment of the ultrasound beam to the aortic or pulmonary outflow
      tracts is essential to acquire accurate signals. This study aimed to investigate
      the influence of different positions on the acquisition of Doppler signals using
      a noninvasive transcutaneous Doppler ultrasound. This was a prospective
      observational crossover study. Two operators performed hemodynamics measurements
      on each subject in supine, sitting, semirecumbent, passive leg raising (PLR) 20
      degrees , and PLR 60 degrees  positions using both aortic and pulmonary
      approaches. All Doppler flow profile images were assessed using the Fremantle and
      Prince of Wales Hospital criteria. Time required to obtain Doppler signals was
      recorded. A total of 60 subjects (50% males) aged 18-60 years old were
      investigated. In both sitting and semirecumbent positions, aortic stroke volume
      indexes (SVIs) and cardiac indexes (CIs) were significantly lower than those in
      the other three positions while the pulmonary CIs were comparable to that in the
      supine position. In the sitting position, the aortic signal qualities were lower
      and the time to obtain the pulmonary Doppler signals was prolonged. Instead, the
      signal quality and the time to obtain the Doppler signals in the semirecumbent
      position were similar to those in the other three positions using the pulmonary
      approach. PLR did not cause a significant increase in SVI regardless of the
      degree of leg elevation. These data show that it is feasible to perform the
      noninvasive transcutaneous Doppler ultrasound using the pulmonary approach in the
      semirecumbent position for patients unable to maintain the supine position. The
      aortic approach in the sitting and semirecumbent positions is not suitable as it
      is not sufficiently reliable. 

PMID- 24303148
TI  - Aldosterone and angiotensin II induce protein aggregation in renal proximal
      tubules.
AB  - Renal tubules are highly active transporting epithelia and are at risk of protein
      aggregation due to high protein turnover and/or oxidative stress. We hypothesized
      that the risk of aggregation was increased upon hormone stimulation and assessed
      the state of the intracellular protein degradation systems in the kidney from
      control rats and rats receiving aldosterone or angiotensin II treatment for 7
      days. Control rats formed both aggresomes and autophagosomes specifically in the
      proximal tubules, indicating a need for these structures even under baseline
      conditions. Fluorescence sorted aggresomes contained various rat keratins known
      to be expressed in renal tubules as assessed by protein mass spectrometry.
      Aldosterone administration increased the abundance of the proximal tubular
      aggresomal protein keratin 5, the ribosomal protein RPL27, ataxin-3, and the
      chaperone heat shock protein 70-4 with no apparent change in the aggresome
      autophagosome markers. Angiotensin II induced aggregation of RPL27 specifically
      in proximal tubules, again without apparent change in antiaggregating proteins or
      the aggresome-autophagosome markers. Albumin endocytosis was unaffected by the
      hormone administration. Taken together, we find that the renal proximal tubules
      display aggresome formation and autophagy. Despite an increase in aggregation
      prone protein load in these tubules during hormone treatment, renal proximal
      tubules seem to have sufficient capacity for removing protein aggregates from the
      cells. 

PMID- 24303149
TI  - Quantifying left ventricular trabeculae function - application of image-based
      fractal analysis.
AB  - The ventricular-blood interface is geometrically complex due to the presence of
      ventricular trabeculae carneae (VTC). We introduce a new image-based framework to
      quantify VTC function using high-resolution computed tomography (CT) imaging and
      offer new insights into the active role of VTCs during ejection. High-resolution
      Cine CT scans of a patient with normal cardiac function were acquired at a
      resolution of 0.77 mm per pixel at 10 phases of the cardiac cycle. The images
      were segmented and the VTC surface was obtained by triangulating the segmented
      data. Fractal dimension of the VTC surface was calculated for each cardiac phase
      as a function of scale size using the box-counting algorithm. The fractal
      dimension, D corresponding to VTCs ranged between 2.05 and 2.2 and varied as a
      function of time during the cardiac cycle. Fractal dimension is highest at
      diastole and lowest at peak systole with the change being significantly different
      (P < 0.003). This variation of D when plotted against stroke volume (i.e., D-V
      loop) revealed an active VTC role due to hysteresis in the loop. Physically the
      hysteresis in the D-V loop indicates a new mechanical function of VTCs as
      structures that provide mechanical leverage during early systolic ejection
      through contraction. VTC relaxation is noted to occur during late diastole at
      larger ventricular volume. D-V loop of VTCs quantifies VTC function. A new
      dynamic physical role of VTCs is suggested by way of mechanical leverage, as
      opposed to the traditionally accepted passive role. 

PMID- 24303150
TI  - Monocarboxylate transporter expression at the onset of skeletal muscle
      regeneration.
AB  - The onset of skeletal muscle regeneration is characterized by proliferating
      myoblasts. Proliferating myoblasts have an increased energy demand and lactate
      exchange across the sarcolemma can be used to address this increased demand.
      Monocarboxylate transporters (MCTs) are involved in lactate transport across the
      sarcolemma and are known to be affected by various physiological stimuli.
      However, MCT expression at the onset of skeletal muscle regeneration has not been
      determined. The purpose of this study was to determine if skeletal muscle
      regeneration altered MCT expression in regenerating tibialis anterior (TA)
      muscle. Male C57/BL6 mice were randomly assigned to either a control (uninjured)
      or bupivacaine (injured) group. Three days post injection, the TA was extracted
      for determination of protein and gene expression. A 21% decrease in muscle mass
      to tibia length (2.4 +/- 0.1 mg/mm vs. 1.9 +/- 0.2 mg/mm, P < 0.02) was observed.
      IGF-1 and MyoD gene expression increased 5.0-fold (P < 0.05) and 3.5-fold (P <
      0.05), respectively, 3 days post bupivacaine injection. MCT-1 protein was
      decreased 32% (P < 0.03); however, MCT-1 gene expression was not altered. There
      was no difference in MCT4 protein or gene expression. Lactate dehydrogenase (LDH)
      A protein expression increased 71% (P < 0.0004). Protein levels of LDH-B and
      mitochondrial enzyme cytochrome C oxidase subunit decreased 3 days post
      bupivacaine injection. CD147 and PKC-theta protein increased 64% (P < 0.03) and
      79% (P < 0.02), respectively. MCT1 but not MCT4 expression is altered at the
      onset of skeletal muscle regeneration possibly in an attempt to regulate lactate
      uptake and use by skeletal muscle cells. 

PMID- 24303152
TI  - Glial cells modulate the synaptic transmission of NTS neurons sending projections
      to ventral medulla of Wistar rats.
AB  - There is evidence that sympathoexcitatory and respiratory responses to
      chemoreflex activation involve ventrolateral medulla-projecting nucleus tractus
      solitarius (NTS) neurons (NTS-VLM neurons) and also that ATP modulates this
      neurotransmission. Here, we evaluated whether or not astrocytes is the source of
      endogenous ATP modulating the synaptic transmission in NTS-VLM neurons. Synaptic
      activities of putative astrocytes or NTS-VLM neurons were recorded using whole
      cell patch clamp. Tractus solitarius (TS) stimulation induced TS-evoked
      excitatory postsynaptic currents (TS-eEPSCs) in NTS-VLM neurons as well in NTS
      putative astrocytes, which were also identified by previous labeling.
      Fluoracetate (FAC), an inhibitor of glial metabolism, reduced TS-eEPSCs amplitude
      (-85.6 +/- 16 vs. -39 +/- 7.1 pA, n = 12) and sEPSCs frequency (2.8 +/- 0.5 vs.
      1.8 +/- 0.46 Hz, n = 10) in recorded NTS-VLM neurons, indicating a gliomodulation
      of glutamatergic currents. To verify the involvement of endogenous ATP a
      purinergic antagonist was used, which reduced the TS-eEPSCs amplitude (-207 +/-
      50 vs. -149 +/- 50 pA, n = 6), the sEPSCs frequency (1.19 +/- 0.2 vs. 0.62 +/-
      0.11 Hz, n = 6), and increased the paired-pulse ratio (PPR) values (~20%) in NTS
      VLM neurons. Simultaneous perfusion of Pyridoxalphosphate-6-azophenyl-2',5'
      disulfonic acid (iso-PPADS) and FAC produced reduction in TS-eEPSCs similar to
      that observed with iso-PPADS or FAC alone, indicating that glial cells are the
      source of ATP released after TS stimulation. Extracellular ATP measurement showed
      that FAC reduced evoked and spontaneous ATP release. All together these data show
      that putative astrocytes are the source of endogenous ATP, which via activation
      of presynaptic P2X receptors, facilitates the evoked glutamate release and
      increases the synaptic transmission efficacy in the NTS-VLM neurons probably
      involved with the peripheral chemoreflex pathways. 

PMID- 24303153
TI  - Inhibiting Amadori-modified albumin formation improves biomarkers of podocyte
      damage in diabetic rats.
AB  - Recent studies have shown that urinary excretion of podocyte proteins is an
      indicator of podocyte injury, and that podocyte abnormalities and elevated
      concentrations of Amadori-modified glycated albumin (AGA) are linked to the
      development of diabetic nephropathy and to each other. We evaluated relationships
      between urinary markers of podocyte damage, increased AGA and filtration function
      in rats made diabetic by streptozotocin injection and treated for 8 weeks with a
      compound that inhibits the formation of AGA, with age-matched nondiabetic and
      diabetic rats serving as controls. Blood and urine were collected for measurement
      of glycated albumin, creatinine, albumin, nephrin, podocalyxin, and betaig-h3
      protein. The elevated circulating concentrations of glycated albumin and higher
      urinary levels of these podocyte markers as well as of albumin that were observed
      in diabetic rats compared with nondiabetic controls were significantly reduced in
      animals receiving test compound, and decrease in urinary biomarkers correlated
      with reduction in AGA. The results provide evidence that lowering the
      concentration of AGA, independent of filtration status and hyperglycemia, reduces
      urinary nephrin, podocalyxin, and betaig-h3 protein, linking the increased
      glycated albumin associated with diabetes to podocyte abnormalities and shedding
      of podocyte proteins into the urine. 

PMID- 24303154
TI  - Skeletal muscle PLIN3 and PLIN5 are serine phosphorylated at rest and following
      lipolysis during adrenergic or contractile stimulation.
AB  - In adipose tissue, access of adipose triglyceride and hormone-sensitive lipases
      (ATGL and HSL) to the lipid droplet depends on PLIN1 phosphorylation, however,
      PLIN1 is not expressed in skeletal muscle and the phosphorylation of the
      expressed PLINs has yet to be investigated. Further, direct interactions between
      skeletal muscle PLINs and HSL are unknown. We investigated the isolated and
      combined effects of epinephrine and contraction on PLIN-to-lipase interactions as
      well as phosphorylation. Isolated rat solei were assigned to one of four 30 min
      in vitro conditions (25 degrees C): (1) rest; (2) intermittent tetanic
      stimulation (60 Hz for 150 msec; train rate 20/min); (3) 5 nmol/L epinephrine;
      (4) intermittent tetanic stimulation and 5 nmol/L epinephrine.
      Immunoprecipitation of serine phosphorylated proteins followed by Western
      blotting for PLIN2, PLIN3, PLIN5, revealed that only PLIN2 is not phosphorylated
      under any of the experimental conditions. This is the first study to show that in
      whole rat skeletal muscle PLIN3 and PLIN5 are serine phosphorylated. The degree
      of serine phosphorylation remained unchanged following adrenergic and/or
      contractile stimulation. Oil red O staining of muscle sections for lipid content
      shows a significant decrease following each condition, confirming lipolysis
      occurred (P < 0.05). PLIN2, 3, and 5 all interact with HSL and ATGL, but these
      interactions were unchanged following treatments. Our results show that in
      skeletal muscle, PLIN2 is not serine phosphorylated at rest or with lipolytic
      stimulation and that while PLIN3, PLIN5 are serine phosphorylated at rest, the
      degree of phosphorylation does not change with lipolytic stimulation. 

PMID- 24303155
TI  - Nephrin missense mutations: induction of endoplasmic reticulum stress and cell
      surface rescue by reduction in chaperone interactions.
AB  - Nephrin, an important component of the podocyte filtration slit diaphragm, plays
      a key role in the maintenance of glomerular permselectivity. Mutations in nephrin
      lead to proteinuria and congenital nephrotic syndrome. Nephrin undergoes
      posttranslational modifications in the endoplasmic reticulum (ER) prior to export
      to the plasma membrane. We examined the effects of human nephrin disease
      associated missense mutations on nephrin folding in the ER and on cellular
      trafficking in cultured cells. Compared with wild-type (WT) nephrin, the mutants
      showed impaired glycosylation and enhanced association with the ER chaperone,
      calnexin, as well as accumulation in the ER. Nephrin mutants demonstrated
      enhanced ubiquitination, and they underwent ER-associated degradation. Certain
      nephrin mutants did not traffic to the plasma membrane. Expression of nephrin
      mutants resulted in the stimulation of the activating transcription factor-6
      pathway of the unfolded protein response, and an increase in the ER chaperone,
      Grp94. We treated cells with castanospermine (an inhibitor of glucosidase I) in
      order to decrease the association of nephrin mutants with calnexin.
      Castanospermine increased plasma membrane expression of nephrin mutants; however,
      full glycosylation and signaling activity of the mutants were not restored.
      Modulation of ER quality control mechanisms represents a potential new approach
      to development of therapies for proteinuric kidney disease, including congenital
      nephrotic syndrome. 

PMID- 24303156
TI  - Evidence for centrally induced cholinergic vasodilatation in skeletal muscle
      during voluntary one-legged cycling and motor imagery in humans.
AB  - We have recently reported that central command contributes to increased blood
      flow in both noncontracting and contracting vastus lateralis (VL) muscles at the
      early period of voluntary one-legged cycling. The purpose of this study was to
      examine whether sympathetic cholinergic vasodilatation mediates the increases in
      blood flows of both muscles during one-legged exercise. Following intravenous
      administration of atropine (10 MUg/kg), eight subjects performed voluntary 1-min
      one-legged cycling (at 35% of maximal voluntary effort) and mental imagery of the
      exercise. The relative concentrations of oxygenated- and deoxygenated-hemoglobin
      (Oxy- and Deoxy-Hb) in the bilateral VL were measured as an index of muscle
      tissue blood flow with near-infrared spectroscopy (NIRS). The Oxy-Hb in both
      noncontracting and contracting VL increased at the early period of one-legged
      cycling, whereas the Deoxy-Hb did not alter at that period. Atropine blunted (P <
      0.05) the Oxy-Hb responses of both VL muscles but did not affect the Deoxy-Hb
      responses. The time course and magnitude of the atropine-sensitive component in
      the Oxy-Hb response were quite similar between the noncontracting and contracting
      VL muscles. With no changes in the Deoxy-Hb and hemodynamics, imagery of one
      legged cycling induced the bilateral increases in the Oxy-Hb, which were
      completely abolished by atropine. In contrast, imagery of a circle (with no
      relation to exercise) did not alter the NIRS signals, irrespective of the
      presence or absence of atropine. It is concluded that central command evokes
      cholinergic vasodilatation equally in bilateral VL muscles during voluntary one
      legged cycling and motor imagery. 

PMID- 24303157
TI  - The effects of tumor necrosis factor-alpha on systolic and diastolic function in
      rat ventricular myocytes.
AB  - The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is
      associated with myocardial dysfunction observed in sepsis and septic shock. There
      are two fundamental components to this dysfunction. (1) systolic dysfunction; and
      (2) diastolic dysfunction. The aim of these experiments was to determine if any
      aspect of whole-heart dysfunction could be explained by alterations to global
      intracellular calcium ([Ca(2+)]i), contractility, and [Ca(2+)]i handling, by TNF
      alpha, at the level of the individual rat myocyte. We took an integrative
      approach to simultaneously measure [Ca(2+)]i, contractility and sarcolemmal Ca
      fluxes using the Ca indicator fluo-3, video edge detection, and the perforated
      patch technique, respectively. All experiments were performed at 37 degrees C.
      The effects of 50 ng/mL TNF-alpha were immediate and sustained. The amplitude of
      systolic [Ca(2+)]i was reduced by 31% and systolic shortening by 19%. Diastolic
      [Ca(2+)]i, myocyte length and relaxation rate were not affected, nor were the
      activity of the [Ca(2+)]i removal mechanisms. The reduction in systolic [Ca(2+)]i
      was associated with a 14% reduction in sarcoplasmic reticulum (SR) content and a
      11% decrease in peak L-type Ca current (IC a-L). Ca influx was decreased by 7%
      associated with a more rapid IC a-L inactivation. These data show that at the
      level of the myocyte, TNF-alpha reduces SR Ca which underlies a reduction in
      systolic [Ca(2+)]i and thence shortening. Although these findings correlate well
      with aspects of systolic myocardial dysfunction seen in sepsis, in this model,
      acutely, TNF-alpha does not appear to provide a cellular mechanism for sepsis
      related diastolic myocardial dysfunction. 

PMID- 24303159
TI  - The contribution of synaptic location to inhibitory gain control in pyramidal
      cells.
AB  - THE ACTIVITY OF PYRAMIDAL CELLS IS CONTROLLED BY TWO OPPOSING FORCES: synaptic
      inhibition and synaptic excitation. Interestingly, these synaptic inputs are not
      distributed evenly across the dendritic trees of cortical pyramidal cells.
      Excitatory synapses are densely packed along only the more peripheral dendrites,
      but are absent from the proximal stems and the soma. In contrast, inhibitory
      synapses are located throughout the dendritic tree, the soma, and the axon
      initial segment. Thus both excitatory and inhibitory inputs exist on the
      peripheral dendritic tree, while the proximal segments only receive inhibition.
      The functional consequences of this uneven organization remain unclear. We used
      both optogenetics and dynamic patch clamp techniques to simulate excitatory
      synaptic conductances in pyramidal cells, and then assessed how their firing
      output is modulated by gamma-amino-butyric acid type A (GABAA) receptor
      activation at different regions of the somatodendritic axis. We report here that
      activation of GABAA receptor on the same dendritic compartment as excitatory
      inputs causes a rightwards shift in the function relating firing rate to
      excitatory conductance (the input-output function). In contrast, GABAA receptor
      activation proximal to the soma causes both a rightwards shift and also a
      reduction in the maximal firing rate. The experimental data are well reproduced
      in a simple, four compartmental model of a neuron with inhibition either on the
      same compartment, or proximal, to the excitatory drive. 

PMID- 24303160
TI  - Cholecystokinin receptors in Atlantic salmon: molecular cloning, gene expression,
      and structural basis.
AB  - The peptide hormone cholecystokinin (CCK) exerts a wide range of digestive and
      CNS-related physiological signaling via CCK receptors in brain and gut. There is
      very limited information available on these receptors in Atlantic salmon. The aim
      of this study was to characterize CCK receptors in gut and brain of salmon. We
      have identified and cloned one CCK-1 receptor and duplicates of CCK-2 receptor in
      salmon. The phylogenetic analysis indicates the existence of one common ancestor
      gene for all CCK receptors. CCK-1R mRNA is highly expressed in pancreas followed
      by midgut, hindgut, gallbladder, and stomach indicating an involvement in
      pancreatic regulation and gallbladder contractions. CCK-2R1/gastrin mRNA is
      expressed at high levels in midgut and at relatively low levels in stomach,
      gallbladder, and pancreas. We postulate CCK-2R1/gastrin receptor to have gastrin
      related functions because of its distribution and abundance in gastro-intestinal
      (GI) tissues. CCK-2R2 is relatively abundant in brain but has low expression
      levels in gut tissues supporting the hypothesis for involvement in the gut-brain
      signaling. Major functional motifs and ligand interaction sites in salmon are
      conserved with that of mammals. This information will be instrumental for
      comparative studies and further targeting receptor activation and selectivity of
      biological responses of CCK in salmon. 

PMID- 24303161
TI  - Nutrient ingestion increased mTOR signaling, but not hVps34 activity in human
      skeletal muscle after sprint exercise.
AB  - Nutrient provision after sprint exercise enhances mammalian target of rapamycin
      (mTOR) signaling. One suggested that nutrient sensor is the class III
      phosphatidylinositol 3-kinase, vacuolar protein sorting 34 (Vps34), not
      previously studied in human skeletal muscle. It is hypothesized that oral
      ingestion of essential amino acids (EAA) and carbohydrates (Carb) increases Vps34
      activity and mTOR signaling in human skeletal (hVps34) muscle after sprint
      exercise. Nine subjects were performed 3 * 30-sec all-out sprints with or without
      ingestion of EAA + Carb or placebo drinks in a randomized order with a month
      interval. Muscle biopsies were performed at rest and 140 min after last sprint
      and analyzed for p-mTOR, p-p70S6k, p-eEF2 and for hVps34 activity and hVps34
      protein content. Venous blood samples were collected and analyzed for amino
      acids, glucose, lactate, and insulin. During the sprint exercise session, EAA,
      glucose, and insulin in blood increased significantly more in EAA + Carb than in
      placebo. P-mTOR and p-p70S6k were significantly increased above rest in EAA +
      Carb (P = 0.03, P = 0.007) 140 min after last sprint, but not in placebo.
      Activity and protein expression of hVps34 were not significantly changed from
      rest in EAA + Carb 140 min after the last sprint. However, hVps34 activity and
      protein expression tended to increase in placebo (both P = 0.08). In conclusion,
      on the contrary to the hypothesis, no increase in activation of hVps34 was found
      following sprint exercise in EAA + Carb condition. In spite of this, the results
      support an activation of mTOR during this condition. However, this does not
      exclude the permissive role of hVps34 in mediating the amino acid-induced
      activation of mTOR and muscle protein synthesis. 

PMID- 24303162
TI  - Gene expression profiles in engineered cardiac tissues respond to mechanical
      loading and inhibition of tyrosine kinases.
AB  - Engineered cardiac tissues (ECTs) are platforms to investigate cardiomyocyte
      maturation and functional integration, the feasibility of generating tissues for
      cardiac repair, and as models for pharmacology and toxicology bioassays. ECTs
      rapidly mature in vitro to acquire the features of functional cardiac muscle and
      respond to mechanical load with increased proliferation and maturation. ECTs are
      now being investigated as platforms for in vitro models for human diseases and
      for pharmacologic screening for drug toxicities. We tested the hypothesis that
      global ECT gene expression patterns are complex and sensitive to mechanical
      loading and tyrosine kinase inhibitors similar to the maturing myocardium. We
      generated ECTs from day 14.5 rat embryo ventricular cells, as previously
      published, and then conditioned constructs after 5 days in culture for 48 h with
      mechanical stretch (5%, 0.5 Hz) and/or the p38 MAPK (p38 mitogen-activated
      protein kinase) inhibitor BIRB796. RNA was isolated from individual ECTs and
      assayed using a standard Agilent rat 4 * 44k V3 microarray and Pathway Analysis
      software for transcript expression fold changes and changes in regulatory
      molecules and networks. Changes in expression were confirmed by quantitative
      polymerase chain reaction (q-PCR) for selected regulatory molecules. At the
      threshold of a 1.5-fold change in expression, stretch altered 1559 transcripts,
      versus 1411 for BIRB796, and 1846 for stretch plus BIRB796. As anticipated, top
      pathways altered in response to these stimuli include cellular development,
      cellular growth and proliferation; tissue development; cell death, cell
      signaling, and small molecule biochemistry as well as numerous other pathways.
      Thus, ECTs display a broad spectrum of altered gene expression in response to
      mechanical load and/or tyrosine kinase inhibition, reflecting a complex
      regulation of proliferation, differentiation, and architectural alignment of
      cardiomyocytes and noncardiomyocytes within ECT. 

PMID- 24303163
TI  - Pericellular Ca(2+) recycling potentiates thrombin-evoked Ca(2+) signals in human
      platelets.
AB  - We have previously demonstrated that Na(+)/Ca(2+) exchangers (NCXs) potentiate
      Ca(2+) signaling evoked by thapsigargin in human platelets, via their ability to
      modulate the secretion of autocoids from dense granules. This link was confirmed
      in platelets stimulated with the physiological agonist, thrombin, and experiments
      were performed to examine how Ca(2+) removal by the NCX modulates platelet dense
      granule secretion. In cells loaded with the near-membrane indicator FFP-18,
      thrombin stimulation was observed to elicit an NCX-dependent accumulation of
      Ca(2+) in a pericellular region around the platelets. To test whether this
      pericellular Ca(2+) accumulation might be responsible for the influence of NCXs
      over platelet function, platelets were exposed to fast Ca(2+) chelators or had
      their glycocalyx removed. Both manipulations of the pericellular Ca(2+) rise
      reduced thrombin-evoked Ca(2+) signals and dense granule secretion. Blocking
      Ca(2+)-permeable ion channels had a similar effect, suggesting that Ca(2+)
      exported into the pericellular region is able to recycle back into the platelet
      cytosol. Single cell imaging with extracellular Fluo-4 indicated that thrombin
      evoked rises in extracellular [Ca(2+)] occurred within the boundary described by
      the cell surface, suggesting their presence within the open canalicular system
      (OCS). FFP-18 fluorescence was similarly distributed. These data suggest that
      upon thrombin stimulation, NCX activity creates a rise in [Ca(2+)] within the
      pericellular region of the platelet from where it recycles back into the platelet
      cytosol, acting to both accelerate dense granule secretion and maintain the
      initial rise in cytosolic [Ca(2+)]. 

PMID- 24303164
TI  - The spontaneous electrical activity of neurons in leech ganglia.
AB  - Using the newly developed voltage-sensitive dye VF2.1.Cl, we monitored
      simultaneously the spontaneous electrical activity of ~80 neurons in a leech
      ganglion, representing around 20% of the entire neuronal population. Neurons
      imaged on the ventral surface of the ganglion either fired spikes regularly at a
      rate of 1-5 Hz or fired sparse spikes irregularly. In contrast, neurons imaged on
      the dorsal surface, fired spikes in bursts involving several neurons. The overall
      degree of correlated electrical activity among leech neurons was limited in
      control conditions but increased in the presence of the neuromodulator serotonin.
      The spontaneous electrical activity in a leech ganglion is segregated in three
      main groups: neurons comprising Retzius cells, Anterior Pagoda, and Annulus
      Erector motoneurons firing almost periodically, a group of neurons firing
      sparsely and randomly, and a group of neurons firing bursts of spikes of varying
      durations. These three groups interact and influence each other only weakly. 

PMID- 24303165
TI  - The manipulation of strain, when stress is controlled, modulates in vivo tendon
      mechanical properties but not systemic TGF-beta1 levels.
AB  - Modulators of loading-induced in vivo adaptations in muscle-tendon complex (MTC)
      mechanical properties remain unclear. Similarly contentious, is whether changes
      in MTC characteristics are associated with growth factor levels. Four groups were
      subjected to varying magnitudes of stress/strain: Group 1 trained with the MTC at
      a shortened position (MTCS; n = 10); Group 2 at a lengthened position (MTCL; n =
      11; stress levels matched to MTCS); Group 3 over a wide range of motion (MTCX; n
      = 11); and Group 4 (n = 10) was the control population (no training). Patella
      tendon Stiffness (P < 0.001), Young's modulus, and quadriceps torque (P < 0.05)
      increments (only seen in the training groups), showed MTCL and MTCX groups
      responses to be superior to those of MTCS (P < 0.05). In addition, MTCL and MTCX
      better maintained adaptations compared to MTCS (P < 0.05) following detraining,
      with a pattern of slower loss of improvements at the early phase of detraining in
      all training groups. There were no significant changes (P > 0.05) in antagonist
      cocontraction, patella tendon dimensions or circulating transforming growth
      factor beta (TGF-beta1) levels following training or detraining in any of the
      groups. We conclude that chronically loading the MTC in a relatively lengthened
      position (which involves greater strains) enhances its mechanical properties,
      more so than loading in a shortened position. This is true even after normalizing
      for internal stress. The underlying endocrine mechanisms do not appear to be
      mediated via TGF-beta1, at least not at the systemic level. Our findings have
      implications with regard to the effectiveness of eccentric loading on improved
      tendon structural and mechanical properties. 

PMID- 24303166
TI  - Hypovolemia explains the reduced stroke volume at altitude.
AB  - During acute altitude exposure tachycardia increases cardiac output (Q) thus
      preserving systemic O2 delivery. Within days of acclimatization, however, Q
      normalizes following an unexplained reduction in stroke volume (SV). To
      investigate whether the altitude-mediated reduction in plasma volume (PV) and
      hence central blood volume (CBV) is the underlying mechanism we
      increased/decreased CBV by means of passive whole body head-down (HDT) and head
      up (HUT) tilting in seven lowlanders at sea level (SL) and after 25/26 days of
      residence at 3454 m. Prior to the experiment on day 26, PV was normalized by
      infusions of a PV expander. Cardiovascular responses to whole body tilting were
      monitored by pulse contour analysis. After 25/26 days at 3454 m PV and blood
      volume decreased by 9 +/- 4% and 6 +/- 2%, respectively (P < 0.001 for both). SV
      was reduced compared to SL for each HUT angle (P < 0.0005). However, the expected
      increase in SV from HUT to HDT persisted and ended in the same plateau as at SL,
      albeit this was shifted 18 +/- 20 degrees  toward HDT (P = 0.019). PV expansion
      restored SV to SL during HUT and to an ~8% higher level during HDT (P = 0.003).
      The parallel increase in SV from HUT to HDT at altitude and SL to a similar
      plateau demonstrates an unchanged dependence of SV on CBV, indicating that the
      reduced SV during HUT was related to an attenuated CBV for a given tilt angle.
      Restoration of SV by PV expansion rules out a significant contribution of other
      mechanisms, supporting that resting SV at altitude becomes reduced due to a
      hypovolemia. 

PMID- 24303167
TI  - Effects of dipeptidyl peptidase-4 inhibition in an animal model of experimental
      asthma: a matter of dose, route, and time.
AB  - The CD26-associated enzymatic activity of dipeptidyl peptidase-4 (DPP4) as well
      as the recruitment of CD26(+) T cells increase under allergic airway
      inflammation. Furthermore, genetic deficiency of CD26/DPP4 exerts protective
      effects in experimental asthma. Therefore, CD26/DPP4 might represent a novel
      therapeutic target in asthma. To study the effects of pharmacological inhibition
      of DPP4 on allergic airway inflammation the DPP4-inhibitor isoleucine
      thiazolidide was tested using different doses at different time points (at
      sensitization, immediately before and simultaneously with the allergen challenge,
      as well as continuously via drinking water), and different routes
      (intraperitoneal, oral, and by inhalation). Allergic-like airway inflammation was
      induced in Fischer 344 rats (Charles River) sensitized against ovalbumin (OVA)
      using OVA aerosols. Intraperitoneal application of the DPP4 inhibitor showed
      effects neither at sensitization nor at challenge, whereas a continuous
      application via drinking water using high doses of the inhibitor led to an
      aggravation of the histomorphological signs of airway inflammation. In contrast,
      aerosolization of the DPP4 inhibitor simultaneously with the allergen
      significantly reduced airway hyperresponsiveness and ameliorated
      histopathological signs compared to controls. In addition, this treatment
      resulted in increased mRNA levels of surfactant proteins, suggesting an
      involvement of DPP4 inhibitors in surfactant metabolism in OVA-challenged rats.
      Continuous systemic inhibition of DPP4 via the oral route aggravates allergic
      airway inflammation. In contrast, topical inhibition of DPP4 exerts potential
      protective effects, and further research in humans is needed. 

PMID- 24303168
TI  - Multigenerational effects of fetal-neonatal iron deficiency on hippocampal BDNF
      signaling.
AB  - Fetal-neonatal iron deficiency induces adult learning impairments concomitant
      with changes in expression of key genes underlying hippocampal learning and
      memory in spite of neonatal iron replenishment. Notably, expression of brain
      derived neurotrophic factor (BDNF), a gene critical for neuronal maturation and
      synaptic plasticity, is lowered both acutely and in adulthood following early
      life iron deficiency. Although the mechanism behind its long-term downregulation
      remains unclear, epigenetic modification in BDNF, as seen in other models of
      early-life adversity, may play a role. Given that early iron deficiency occurs
      during critical periods in both hippocampal and gonadal development, we
      hypothesized that the iron-sufficient offspring (F2 IS) of formerly iron
      deficient (F1 FID) rats would show a similar suppression of the BDNF gene as
      their parents. We compared hippocampal mRNA levels of BDNF and functionally
      related genes among F1 IS, F1 ID, and F2 IS male rats at postnatal day (P) 15 and
      P65 using RT-qPCR. As expected, the F1 ID group showed a downregulation of BDNF
      and associated genes acutely at P15 and chronically at P65. However, the F2 IS
      group showed an upregulation of these genes at P15, returning to control levels
      at P65. These results demonstrate that adverse effects of early iron deficiency
      on hippocampal gene expression observed in the F1 are not present in the F2
      generation, suggesting differential effects of nutritionally induced epigenetic
      programing during the critical periods of hippocampal and gonadal development. 

PMID- 24303169
TI  - A novel experimental model of orthopedic trauma with acute kidney injury in obese
      Zucker rats.
AB  - Obesity is associated with an increased risk of acute kidney injury (AKI) after
      blunt traumatic injury in humans. Because limitations exist in studying trauma in
      human patients, animal models are necessary to elucidate mechanisms of remote
      organ injury after trauma. We developed a model of severe orthopedic trauma in
      lean (LZ) and obese (OZ) Zucker rats, in which OZ develop greater kidney
      dysfunction after trauma than LZ. Orthopedic trauma was inflicted via bilateral
      hindlimb soft tissue injury, fibula fracture, and injection of homogenized bone
      components. Mean arterial pressure (MAP) and heart rate (HR) were measured for 6
      h after trauma, and again at 24 h after trauma. Urine was collected for 24 h
      before and after trauma to measure urine albumin excretion. Glomerular filtration
      rate (GFR), renal plasma flow (RPF), plasma interleukin-6 (IL-6), and renal
      macrophage infiltration (ED-1 [CD68 Antibody] immunostaining) were measured in
      animals with and without trauma. MAP and HR were similar between LZ and OZ
      throughout the study, with the exception that OZ had a 18 mmHg lower pressure 24
      h posttrauma. GFR and RPF were decreased significantly (~50%), while urine
      albumin excretion, plasma IL-6, and renal ED-1-positive cells were increased in
      OZ 24 h after trauma compared to both OZ without trauma and LZ after trauma. In
      conclusion, these data are consistent with studies in humans that show that AKI
      develops more frequently in obese than in lean individuals. This model will be an
      important experimental tool to better understand the underlying mechanisms of
      poor outcomes after trauma in obese patients. 

PMID- 24303170
TI  - Myocardial oxygenation is maintained during hypoxia when combined with apnea - a
      cardiovascular MR study.
AB  - Oxygenation-sensitive (OS) cardiovascular magnetic resonance (CMR) is used to
      noninvasively measure myocardial oxygenation changes during pharmacologic
      vasodilation. The use of breathing maneuvers with OS CMR for diagnostic purposes
      has been recently proposed based on the vasodilatory effect of Co2, which can be
      enhanced by the additive effect of mild hypoxia. This study seeks to investigate
      this synergistic concept on coronary arteriolar resistance with OS CMR. In nine
      anesthetized swine, normoxemic and mild hypoxemic arterial partial pressure of
      oxygen (Pao2) levels (100 and 80 mmHg) were targeted with three arterial partial
      pressure of carbon dioxide (Paco2) levels of 30, 40, and 50 mmHg. During a 60-sec
      apnea from the set baselines, OS T2*-weighted gradient echo steady-state free
      precession (SSFP) cine series were obtained in a clinical 1.5T magnetic resonance
      imaging (MRI) system. Arterial blood gases were acquired prior to and after
      apnea. Changes in global myocardial signal intensity (SI) were measured. Although
      a greater drop in arterial oxygen saturation (SaO2) was observed in the hypoxemic
      baselines, myocardial SI increased or was maintained during apnea in all levels
      (n = 6). An observed decrease in left ventricular blood pool SI was correlated
      with the drop in SaO2. Corrected for the arterial desaturation, the calculated SI
      increase attributable to the increase in myocardial blood flow was greater in the
      hypoxemic levels. Both the changes in Paco2 and Pao2 were correlated with
      myocardial SI changes at normoxemia, yet not at hypoxemic levels. Using OS CMR,
      we found evidence that myocardial oxygenation is preserved during hypoxia when
      combined with Co2-increasing maneuvers, indicating synergistic effects of
      hypoxemia and hypercapnia on myocardial blood flow. 

PMID- 24303171
TI  - Neuromuscular adaptations to 4 weeks of intensive drop jump training in well
      trained athletes.
AB  - This study examined the effects of 4 weeks of intensive drop jump training in
      well-trained athletes on jumping performance and underlying changes in
      biomechanics and neuromuscular adaptations. Nine well-trained athletes at high
      national competition level within sprinting and jumping disciplines participated
      in the study. The training was supervised and augmented feedback on performance
      was used to ensure maximal training intensity. The drop jumps were performed with
      minimal contact time and maximal jumping height. Assessment of performance during
      training showed effects of motor learning. Before and after the training
      intervention maximal isometric muscle strength, the biomechanics, muscle activity
      pattern of the lower extremities and the soleus H-reflex and V-wave during drop
      jumping were measured. Maximal jump height and performance index (PI) defined as
      jumping height divided by contact time improved significantly by 11.9% (P =
      0.024) and 16.2% (P = 0.009), respectively. Combined ankle and knee joint peak
      power was significantly increased by 7% after training (P = 0.047). The
      preactivity in the soleus muscle decreased 16% (P = 0.015). The soleus H-reflex
      was unchanged after training, while the soleus V-wave increased significantly at
      45 msec after touchdown. This may indicate an increased drive to the alpha-motor
      neuron pool following training. Muscle strength parameters were unaffected by the
      training. The results demonstrate that 4 weeks of intensive drop jump training
      can improve jumping performance also in well-trained athletes without concomitant
      changes in muscle strength. It is suggested that the behavioral improvement is
      primarily due to neural factors regulating the activation pattern controlling the
      drop jump movement. 

PMID- 24303173
TI  - Evidence for glucocorticoid-mediated hypertension after uninephrectomy.
AB  - Recently, evidence was presented that uninephrectomy induces salt-sensitive
      hypertension in rats. The increase in blood pressure was abrogated by a
      mineralocorticoid receptor antagonist but not by an aldosterone synthase
      inhibitor. Here, we hypothesize that mineralocorticoid receptor activation
      occurred by an 11beta-hydroxy-glucocorticosteroid, as a consequence of
      dysregulated 11beta-hydroxysteroid dehydrogenase enzymes. Therefore, 3-week-old
      Sprague-Dawley rats were either uninephrectomized or sham operated and given a
      normal (0.4%) or high (8%)-salt diet. At week 8, a telemetric device was
      implanted, and during week 13 blood pressure continuously measured and urine was
      collected. The animals were sacrificed thereafter and liver and kidney were
      harvested. Steroid metabolites were analyzed by GC-MS and mRNA assessed by PCR.
      Uninephrectomy caused a distinct salt-sensitive hypertension. The increase in
      blood pressure correlated significantly with a decline in the apparent activity
      of 11beta-hydroxysteroid dehydrogenase 2 and an increase of 11beta-hydroxysteroid
      dehydrogenase 1, when urinary corticosterone metabolites were considered. These
      results were mirrored by the corresponding metabolite ratios assessed in renal
      and liver tissue. Changes in enzyme activities were in part explained by changes
      in the mRNA content. In conclusion, mineralocorticoid receptor-dependent salt
      sensitivity after UNX in rats appears to be mediated by glucocorticoids. 

PMID- 24303172
TI  - Electroencephalographic and early communicative abnormalities in Brattleboro
      rats.
AB  - Reductions in the levels of the neuropeptide vasopressin (VP) and its receptors
      have been associated with schizophrenia. VP is also critical for appropriate
      social behaviors in humans as well as rodents. One of the prominent symptoms of
      schizophrenia is asociality and these symptoms may develop prodromally. A
      reduction in event-related potential (ERP) peak amplitudes is an endophenotype of
      schizophrenia. In this study, we use the Brattleboro (BRAT) rat to assess the
      role of VP deficiency in vocal communication during early development and on
      auditory ERPs during adulthood. BRAT rats had similar vocal communication to wild
      type littermate controls during postnatal days 2 and 5 but the time between
      vocalizations was increased and the power of the vocalizations was reduced
      beginning at postnatal day 9. During adulthood, BRAT rats had deficits in
      auditory ERPs including reduced N40 amplitude and reduced low and high gamma
      intertrial coherence. These results suggest that the role of VP on vocal
      communication is an age-dependent process. Additionally, the deficits in ERPs
      indicate an impairment of auditory information processing related to the
      reduction in VP. Therefore, manipulation of the VP system could provide a novel
      mechanism for treatment for negative symptoms of schizophrenia. 

PMID- 24303174
TI  - Whole-body recruitment of glycocalyx volume during intravenous adenosine
      infusion.
AB  - Adenosine-mediated recruitment of microvascular volume in heart and muscle has
      been suggested to include, in addition to vasodilation of resistance vessels, an
      increased accessibility of the endothelial glycocalyx for flowing plasma as a
      result of an impairment of its barrier properties. The aim of the current study
      was to investigate the effect of systemic intravenous administration of adenosine
      on the glycocalyx-dependent exclusion of circulating blood at a whole-body level.
      In anesthetized goats (N = 6), systemic blood-excluded glycocalyx volume was
      measured by comparing the intravascular distribution volume of the suggested
      glycocalyx accessible tracer dextrans with a molecular weight of 40 kDa (Dex-40)
      to that of circulating plasma, derived from the dilution of labeled red blood
      cells and large vessel hematocrit. Systemic glycocalyx volume was determined at
      baseline and during intravenous infusion of adenosine (157 +/- 11.6 MUg/kg min(
      1)). Blood-inaccessible glycocalyx volume decreased from 458.1 +/- 95.5 to 18.1
      +/- 62.2 mL (P < 0.01) during adenosine administration. While circulating plasma
      volume did not change significantly (617.1 +/- 48.5 vs. 759.2 +/- 47.9 mL, NS),
      the decrease in blood-excluded glycocalyx volume was associated with a decrease
      in Dex-40 distribution volume (from 1075.2 +/- 71.0 to 777.3 +/- 60.0 mL, P <
      0.01). Intravenous administration of adenosine is associated with a robust
      impairment of whole-body glycocalyx barrier properties, reflected by a greatly
      reduced exclusion of circulating blood compared to small dextrans. The observed
      decrease in Dex-40 distribution volume suggests that the reduction in glycocalyx
      volume coincides with a reduction in tracer-accessible vascular volume. 

PMID- 24303175
TI  - Glucocorticoid excess induces long-lasting changes in body composition in male
      C57Bl/6J mice only with high-fat diet.
AB  - Glucocorticoid (GC) overexposure period as observed in Cushing's syndrome (CS) is
      associated with the metabolic syndrome and cardiovascular disease, which persist
      after long-term correction of GC excess. We performed a mouse study to identify
      factors that modulate metabolic recovery from a GC overexposure period. Male
      C57Bl/6J mice, fed a low-fat diet (LFD) or a high-fat diet (HFD), received
      corticosterone (CORT) (50 MUg/mL) or vehicle in the drinking water for 4 weeks,
      followed by an 8-week washout period. Plasma circadian CORT, lipids, insulin, and
      glucose levels were assessed regularly. Hyperinsulinemic-euglycemic clamp and
      body composition were analyzed at week 12 under anesthesia. CORT treatment
      increased plasma CORT levels, food intake, and plasma insulin and lipid levels on
      both diets. CORT treatment abrogation normalized CORT levels, food intake, and
      body weight, whereas plasma insulin levels remained significantly higher in CORT
      treated mice on both diets. Only on a HFD, CORT-treated mice had decreased lean
      body mass and higher fat mass. In conclusion, CORT excess period induces long
      lasting metabolic changes and some are present only on a HFD. These observations
      indicate that diet-dependent CORT effects might contribute to the adverse
      cardiovascular risk profile observed in CS patients, and possibly also in
      subjects exposed to chronic stress. 

PMID- 24303176
TI  - Renal angiotensin II type 1 receptor expression and associated hypertension in
      rats with minimal SHR nuclear genome.
AB  - Angiotensin II (AII) has been linked as a causal factor in several experimental
      models of hypertension (HT) including Okamoto spontaneously hypertensive rats
      (SHR). The transmission and expression of AII type 1 receptors (AT1r) in SHR and
      the development of genetic HT remain unknown. It is hypothesized that tissue
      specific expression of renin-angiotensin system (RAS) genes derived from SHR are
      linked to HT in offspring of SHR crossed with Brown Norway (BN) rats.
      Hypertensive female progeny of BN/SHR matings was backcrossed with founder BN
      males to generate the F1 and five backcross generations (BN/SHR-mt(SHR)). Progeny
      were phenotyped according to normotension (NT: systolic arterial pressure [SAP]
      <= 124 mmHg), borderline hypertension (BHT: 124 <= SAP < 145 mmHg), and HT (SAP
      >= 145 mmHg). Six generations produced more HT (n = 88; 46%) than NT (n = 21;
      11%) offspring. The mRNA expression of the RAS was evaluated in NT (n = 20) and
      HT (n = 20) BN/SHR-mt(SHR) across several generations. Quantitative real-time
      polymerase chain reaction analysis of kidney tissue showed increased expression
      of AII, type 1 receptors (Agtr1a) (~2.5-fold) in HT versus NT rats, while other
      members of both the renal and systemic RAS pathway were not different. Western
      blot analysis from kidney homogenates showed that AT1r protein levels were higher
      (P < 0.05) in backcross generation 3 (BC3) HT versus NT rats. Evaluation of SAP
      as a function of AT1r expression by linear regression indicated positive
      correlation (P < 0.05) in kidney of BC3 BN/SHR-mt(SHR) rats. Thus, elevated
      kidney AT1r expression may be involved in the development of HT in BN/SHR-mt(SHR)
      rats. 

PMID- 24303177
TI  - Activation of RhoA/Rho-kinase pathway accounts for pulmonary endothelial
      dysfunction in patients with chronic obstructive pulmonary disease.
AB  - Recent evidence suggests that activation of RhoA/Rho-kinase accounts for systemic
      and pulmonary endothelial dysfunction in smokers with normal lung function.
      However, its role in patients with chronic obstructive pulmonary disease (COPD)
      has not yet been investigated. The aim of this study was to evaluate the
      regulation of RhoA/Rho-kinase pathway and pulmonary endothelial dysfunction in
      patients with COPD. Pulmonary arteries were obtained from nonsmokers (control
      subjects) and patients with nonhypoxemic and hypoxemic COPD (n = 6-7/group).
      Endothelium-dependent and -independent relaxations were evaluated by
      acetylcholine and sodium nitroprusside, respectively. Gene and protein
      expressions of endothelial nitric oxide synthase (eNOS) were measured by RT-PCR,
      Western blot, and immunohistochemistry. Nitrate, cGMP, and endothelin-1 (ET-1)
      concentrations, as well as Rho-kinase activity were measured by ELISA. Protein
      expressions of total RhoA and GTP-RhoA were measured by Western blot and pull
      down assay, respectively. Endothelium-dependent relaxation, and nitrate and cGMP
      levels were significantly reduced in pulmonary arteries of COPD patients as
      compared with control subjects. Conversely, activity of RhoA/Rho-kinase was
      increased in pulmonary arteries of COPD patients as compared with control
      subjects. In patients with COPD, pulmonary endothelial dysfunction was related to
      the downregulation of eNOS activity and upregulation of RhoA/Rho-kinase activity.

PMID- 24303178
TI  - Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible
      role of kidney.
AB  - There is evidence that dietary fats are important components contributing in bone
      health and that bone mineral density is inversely related to sodium intake. Salt
      loading is also known to impose negative effects on renal function. The present
      study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on
      bone changes imposed by salt loading, highlighting the role of kidney as a
      potential mechanism involved in this effect. Male Wistar rats were divided into
      three groups: control group, salt-loaded group consuming 2% NaCl solution as
      drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1
      g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks.
      Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium,
      potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP),
      creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth
      factor-beta1 (TGF-beta1) were measured. The right tibia and kidney were removed
      for histologic examination and renal immunohistochemical analysis for endothelial
      nitric oxide synthase (eNOS) was performed. The results revealed that omega-3
      reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine,
      urea, and TGF-beta1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3
      as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness,
      decreased osteoclast number, and increased newly formed osteoid bone. Renal
      morphology was found preserved. In conclusion, omega-3 prevents the disturbed
      bone status imposed by salt loading. This osteoprotective effect is possibly
      mediated by attenuation of alterations in Ca(2+), Pi, and ALP, and improvement of
      renal function and arterial blood pressure. 

PMID- 24303179
TI  - Factors that determine directional constraint in ipsilateral hand-foot
      coordinated movements.
AB  - In performing simultaneous rhythmic movements of the ipsilateral hand and foot,
      there are differences in the level of stability between same directional (stable)
      and opposite directional (unstable) movements. This is the directional
      constraint. In this study, we investigated three factors ("interaction in
      efferent process," "interaction of afferent signals," and "error correction")
      proposed to underlie for the directional constraint. We compared the performance
      of three tasks: (1) coordination of actively moved ipsilateral hand and foot, (2)
      active hand movement in coordination with passively moved foot, (3) active hand
      movement not coordinated with a passively moved foot. In each task, both same and
      opposite directional movements were executed. There was no difference between
      performance estimated with success rate for the first and second task. The
      directional constraint appeared in both tasks. Thus, the interaction in efferent
      processes, which was shown to be responsible for the directional constraint in
      bimanual coordination, was not involved with the directional constraint of
      ipsilateral hand-foot coordination. The directional constraint did not appear in
      the third task, which suggested that "interaction of afferent signals" also had
      no contribution. These results indicated that "error correction" must be the most
      critical of these factors for mediating the directional constraint in ipsilateral
      hand-foot coordinated movements. 

PMID- 24303180
TI  - Removal of luminal content protects the small intestine during hemorrhagic shock
      but is not sufficient to prevent lung injury.
AB  - The small intestine plays a key role in the pathogenesis of multiple organ
      failure following circulatory shock. Current results show that reduced perfusion
      of the small intestine compromises the mucosal epithelial barrier, and the
      intestinal contents (including pancreatic digestive enzymes and partially
      digested food) can enter the intestinal wall and transport through the
      circulation or mesenteric lymph to other organs such as the lung. The extent to
      which the luminal contents of the small intestine mediate tissue damage in the
      intestine and lung is poorly understood in shock. Therefore, rats were assigned
      to three groups: No-hemorrhagic shock (HS) control and HS with or without a
      flushed intestine. HS was induced by reducing the mean arterial pressure (30
      mmHg; 90 min) followed by return of shed blood and observation (3 h). The small
      intestine and lung were analyzed for hemorrhage, neutrophil accumulation, and
      cellular membrane protein degradation. After HS, animals with luminal contents
      had increased neutrophil accumulation, bleeding, and destruction of E-cadherin in
      the intestine. Serine protease activity was elevated in mesenteric lymph fluid
      collected from a separate group of animals subjected to intestinal
      ischemia/reperfusion. Serine protease activity was elevated in the plasma after
      HS but was detected in lungs only in animals with nonflushed lumens. Despite
      removal of the luminal contents, lung injury occurred in both groups as
      determined by elevated neutrophil accumulation, permeability, and lung protein
      destruction. In conclusion, luminal contents significantly increase intestinal
      damage during experimental HS, suggesting transport of luminal contents across
      the intestinal wall should be minimized. 

PMID- 24303181
TI  - Left ventricular twist and untwist rate provide reliable measures of ventricular
      function in myocardial ischemia and a wide range of hemodynamic states.
AB  - Although rotational parameters by speckle tracking echocardiography (STE) have
      been previously compared to sonomicrometry and cardiac magnetic resonance
      imaging, few have examined the relationship between left ventricular (LV)
      rotational mechanics and intraventricular measures of load-independent
      contractility, LV stiffness, or ventriculoarterial coupling. The aim of this
      study was to compare the changes in LV rotational indices to intraventricular
      pressure-volume (PV) relationships under a range of inotropic states induced by
      pharmacological interventions, acute ischemia, and changes in preload. In nine
      pigs, simultaneous echocardiographic imaging and LVPV measurements were performed
      during pharmacologically induced high or low inotropy and during acute ischemia
      by ligation of the left anterior descending coronary artery (LAD). Maximal
      ventricular elastance (Emax), arterial elastance (Ea), ventricular-arterial
      coupling (Emax/Ea), dP/dt, tau, and other hemodynamic parameters were determined.
      Dobutamine and esmolol infusions led to inversely correlated changes in
      hemodynamic measurements of LV function. Apical but not basal rotation and
      diastolic rotation rate were decreased by esmolol and increased by dobutamine.
      The LV twist correlates well with Emax (r = 0.83) and Emax/Ea (r = 0.80). Apical
      diastolic rotation rate also correlates with dP/dtmin (r = -0.63), tau (r = 
      0.81), and LV stiffness (r = -0.52). LAD ligation decreased systolic and
      diastolic LV rotation in apical (P < 0.05), but not basal myocardium. Occlusion
      of the inferior vena cava, to reduce preload, increased apical rotation in
      systole and diastole. LV rotational parameters measured by STE provide
      quantitative and reproducible indices of global LV systolic and diastolic
      function during acute changes in hemodynamics. 

PMID- 24303182
TI  - Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide
      in rat middle cerebral arteries.
AB  - Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both
      vasoregulation and antioxidant effects. This study examines the effect of
      diabetes-induced oxidative stress on H2S production and function in rat middle
      cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg,
      i.v.). Middle cerebral artery function was examined using a small vessel myograph
      and superoxide anion generation measured using nicotinamide adenine dinucleotide
      phosphate (NADPH)-dependent lucigenin-enhanced chemiluminescence. Cystathionine
      gamma-lyase (CSE) mRNA expression was measured via RT-PCR. Diabetic rats had
      elevated blood glucose and significantly reduced cerebral artery endothelial
      function. Maximum vasorelaxation to the H2S donor NaHS was unaffected in diabetic
      cerebral arteries and was elicited via a combination of K(+), Cl(-), and Ca(2+)
      channel modulation, although the contribution of Cl(-) channels was significantly
      less in the diabetic cerebral arteries. Vasorelaxation to the H2S precursor l
      cysteine and CSE mRNA were significantly increased in diabetic cerebral arteries.
      Cerebral artery superoxide production was significantly increased in diabetes,
      but this increase was attenuated ex vivo by incubation with the H2S donor NaHS.
      These data confirm that cerebral artery endothelial dysfunction and oxidative
      stress occurs in diabetes. Endogenous H2S production and activity is upregulated
      in cerebral arteries in this model of diabetes. Vasorelaxation responses to
      exogenous H2S are preserved and exogenous H2S attenuates the enhanced cerebral
      artery generated superoxide observed in the diabetic group. These data suggest
      that upregulation of endogenous H2S in diabetes may play an antioxidant and
      vasoprotective role. 

PMID- 24303183
TI  - Oxyntomodulin increases intrinsic heart rate through the glucagon receptor.
AB  - Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM),
      vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously
      shown that OXM influences murine heart rate (HR) independent of the glucagon-like
      peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice
      deficient in the glucagon receptor (Gcgr -/-) that both OXM and glucagon require
      the glucagon receptor for their chronotropic effects on the heart. Furthermore,
      we found that other hormones associated with hunger and satiety (ghrelin, leptin,
      and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the
      IHR. Finally, the resting HR of Gcgr -/- mice was higher than in control mice
      (Gcgr +/+ and Gcgr +/-) at thermal neutral temperature (30 degrees C). Using
      atropine, we demonstrated that Gcgr -/- mice have diminished parasympathetic
      (PNS) influence of the heart at this temperature. Gcgr -/- mice displayed a
      normal bradycardia as compared to controls in response to administration of
      either methacholine (to activate the muscarinic acetylcholine receptor) or
      methoxamine (to activate the baroreflex through agonism of the alpha1 adrenergic
      receptor agonist) suggesting that vagal pathways are intact in the Gcgr -/- mice.
      As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity,
      we suggest OXM may be an alternative to glucagon in the treatment of overdose of
      beta-blockers to elevate HR in clinical conditions. 

PMID- 24303184
TI  - RBC deformability and amino acid concentrations after hypo-osmotic challenge may
      reflect chronic cell hydration status in healthy young men.
AB  - Biomarkers of chronic cell hydration status are needed to determine whether
      chronic hyperosmotic stress increases chronic disease risk in population
      representative samples. In vitro, cells adapt to chronic hyperosmotic stress by
      upregulating protein breakdown to counter the osmotic gradient with higher
      intracellular amino acid concentrations. If cells are subsequently exposed to
      hypo-osmotic conditions, the adaptation results in excess cell swelling and/or
      efflux of free amino acids. This study explored whether increased red blood cell
      (RBC) swelling and/or plasma or urine amino acid concentrations after hypo
      osmotic challenge might be informative about relative chronic hyperosmotic stress
      in free-living men. Five healthy men (20-25 years) with baseline total water
      intake below 2 L/day participated in an 8-week clinical study: four 2-week
      periods in a U-shaped A-B-C-A design. Intake of drinking water was increased by
      +0.8 +/- 0.3 L/day in period 2, and +1.5 +/- 0.3 L/day in period 3, and returned
      to baseline intake (0.4 +/- 0.2 L/day) in period 4. Each week, fasting blood and
      urine were collected after a 750 mL bolus of drinking water, following overnight
      water restriction. The periods of higher water intake were associated with
      significant decreases in RBC deformability (index of cell swelling), plasma
      histidine, urine arginine, and urine glutamic acid. After 4 weeks of higher water
      intake, four out of five participants had 1/2 maximal RBC deformability below 400
      mmol/kg; plasma histidine below 100 MUmol/L; and/or undetectable urine arginine
      and urine glutamic acid concentrations. Work is warranted to pursue RBC
      deformability and amino acid concentrations after hypo-osmotic challenge as
      possible biomarkers of chronic cell hydration. 

PMID- 24303185
TI  - Energy intake and the circadian rhythm of core body temperature in sheep.
AB  - We tested the hypothesis that different levels of energy intake would alter the
      circadian rhythm of core body temperature (Tc) in ovariectomized sheep. We
      measured arterial blood temperature every 5 min while ten sheep were offered a
      maintenance diet, 70% of maintenance requirements, or 150% of maintenance
      requirements, for 12 days, and later fasted for 2 days. The rhythmicity of Tc was
      analyzed for its dominant period and then a least-squares cosine wave was fitted
      to the data that generated a mesor, amplitude, and acrophase for the rhythm. When
      energy intake was less than maintenance requirements we observed a significant
      decrease in the mesor and minimum, and a significant increase in the amplitude
      and goodness of fit, of the body temperature rhythm. Fasting also resulted in a
      decrease in the maximum of the body temperature rhythm. Feeding the sheep to
      excess did not affect the mesor or maximum of the rhythm, but did result in a
      decrease in the goodness of fit of the rhythm in those sheep that consumed more
      energy than when they were on the maintenance diet, indicating that circadian
      rhythmicity was decreased when energy intake increased. Our data indicate that
      modulation of the circadian rhythm of body temperature, characterized by inactive
      phase hypothermia, occurs when energy intake is reduced. The response may be an
      adaptation to energy imbalance in large mammals. 

PMID- 24303186
TI  - Development of a new SonovueTM contrast-enhanced ultrasound approach reveals
      temporal and age-related features of muscle microvascular responses to feeding.
AB  - Compromised limb blood flow in aging may contribute to the development of
      sarcopenia, frailty, and the metabolic syndrome. We developed a novel contrast
      enhanced ultrasound technique using SonovueTM to characterize muscle
      microvasculature responses to an oral feeding stimulus (15 g essential amino
      acids) in young (~20 years) and older (~70 years) men. Intensity-time
      replenishment curves were made via an ultrasound probe "fixed" over the
      quadriceps, with intermittent high mechanical index destruction of microbubbles
      within muscle vasculature. This permitted real-time measures of microvascular
      blood volume (MBV), microvascular flow velocity (MFV) and their product,
      microvascular blood flow (MBF). Leg blood flow (LBF) was measured by Doppler and
      insulin by enzyme-linked immunosorbent assay. Steady-state contrast
      concentrations needed for comparison between different physiological states were
      achieved <150 sec from commencing SonovueTM infusion, and MFV and MBV
      measurements were completed <120 sec thereafter. Interindividual coefficients of
      variation in MBV and MFV were 35-40%, (N = 36). Younger men (N = 6) exhibited
      biphasic vascular responses to feeding with early increases in MBV (+36%, P <
      0.008 45 min post feed) reflecting capillary recruitment, and late increases in
      MFV (+77%, P < 0.008) and MBF (+130%, P < 0.007 195 min post feed) reflecting
      more proximal vessel dilatation. Early MBV responses were synchronized with peak
      insulin but not increased LBF, while later changes in MFV and MBF occurred with
      insulin at post absorptive values but alongside increased LBF. All circulatory
      responses were absent in old men (N = 7). Thus, impaired postprandial circulation
      could impact age-related declines in muscle glucose disposal, protein anabolism,
      and muscle mass. 

PMID- 24303187
TI  - Effect of sexual maturation on muscle gene expression of rainbow trout: RNA-Seq
      approach.
AB  - Muscle degradation occurs as a response to various physiological states that are
      regulated by specific molecular mechanisms. Previously, we characterized the
      metabolic changes of muscle deterioration of the female rainbow trout at full
      sexual maturity and spawning (Salem et al., Physiol. Genomics 2006;28:33-45; J.
      Proteomics 2010;73:778-789). Muscle deterioration in this model represents
      nutrient mobilization as a response to the energetic overdemands of the
      egg/ovarian growth phase. Our recent studies showed that most of the changes in
      muscle growth and quality start 2-3 months before spawning. Gravid fish exhibited
      reduced intramuscular fat that is lower in saturated and monounsaturated fatty
      acids and higher in polyunsaturated fatty acids compared to sterile fish. In this
      study, RNA-Seq was used to explain the mechanisms underlying changes during this
      phase of sexual maturity. Furthermore, to minimize changes due to nutrient
      deficits, fish were fed on a high-plane of nutrition. The RNA-Seq technique
      identified a gene expression signature that is consistent with metabolic changes
      of gravid fish. Gravid fish exhibited increased abundance of transcripts in
      metabolic pathways of fatty acid degradation and up-regulated expression of genes
      involved in biosynthesis of unsaturated fatty acids. In addition, increased
      expression of genes involved in the citric acid cycle and oxidative
      phosphorylation was observed for gravid fish. This muscle transcriptomic
      signature of fish fed on a high nutritional plane is quite distinct from that
      previously described for fish at terminal stages of maturity and suggest that
      female rainbow trout approaching spawning, on high nutritional planes, likely
      mobilize intramuscular fat rather than protein to support gonadal maturation. 

PMID- 24303188
TI  - TRPV4 calcium entry and surface expression attenuated by inhibition of myosin
      light chain kinase in rat pulmonary microvascular endothelial cells.
AB  - In previous studies, blockade or gene deletion of either myosin light chain
      kinase (MLCK) or the mechanogated transient receptor potential vanilloid 4
      (TRPV4) channel attenuated mechanical lung injury. To determine their effects on
      calcium entry, rat pulmonary microvascular endothelial cells (RPMVEC) were
      labeled with fluo-4 and calcium entry initiated with the TRPV4 agonist, 4alpha
      phorbol 12, 13-didecanoate (4alphaPDD). Mean calcium transients peaked at ~25 sec
      and persisted ~500 sec. The 4alphaPDD response was essentially abolished in
      calcium-free media, or after pretreatment with the MLCK inhibitor, ML-7. ML-7
      also attenuated the 4alphaPDD-induced inward calcium current measured directly
      using whole-cell patch clamp. Pretreatment with dynasore, an inhibitor of dynamin
      produced an initial calcium transient followed by a 4alphaPDD transient of
      unchanged peak intensity. Automated averaging of areas under the curve (AUC) of
      calcium transients in individual cells indicated total calcium activity with a
      relationship between treatment groups of ML-7 + 4alphaPDD < 4alphaPDD only <
      dynasore + 4alphaPDD. Measurement of biotinylated surface TRPV4 protein indicated
      a significant reduction after ML-7 pretreatment, but no significant change with
      dynasore treatment. RPMVEC monolayer electrical resistances were decreased by
      only 3% with 10 MUmol/L 4alphaPDD and the response was dose-related. Dynasore
      alone produced a 29% decrease in resistance, but neither ML-7 nor dynasore
      affected the subsequent 4alphaPDD resistance response. These studies suggest that
      MLCK may inhibit mechanogated calcium responses through reduced surface
      expression of stretch activated TRPV4 channels in the plasma membrane. 

PMID- 24303189
TI  - Cellular inhibitor of apoptosis-2 is a critical regulator of apoptosis in airway
      epithelial cells treated with asthma-related inflammatory cytokines.
AB  - Aberrant apoptosis of airway epithelial cells (AECs) is a disease contributing
      feature in the airways of asthmatics. The proinflammatory cytokines tumor
      necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) are increased in
      asthma and have been shown to contribute to apoptosis at the airways. In the
      present study, we investigated the role of the inhibitor of apoptosis protein
      (IAP) family in primary AECs exposed to TNFalpha and IFNgamma. IAPs are potent
      regulators of caspase activity elicited by the intrinsic and extrinsic apoptosis
      pathways. However, while caspase-mediated apoptosis was observed in AECs exposed
      to doxorubicin, it was not observed after cytokine treatment. Instead, AECs
      exhibited proapoptotic changes evidenced by an increased Bax:Bcl2 transcript
      ratio and partial processing of procaspase-3. Examination by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and Western analysis showed
      that proapoptotic changes were associated with a time- and dose-dependent
      induction of cellular IAP-2 (cIAP2), potentiated primarily by IFNgamma. The
      abundance of the IAP antagonists X-linked IAP-associated factor 1 (XAF1) and
      second mitochondria-derived activator of caspases did not change, although a
      moderate nuclear redistribution was observed for XAF1, which was also observed
      for cIAP2. Small interfering RNA (siRNA)-mediated depletion of cIAP2 from AECs
      leads to caspase-3 activation and poly (ADP-ribose) polymerase cleavage, but this
      required extended cytokine exposure to produce a concomitant decrease in cIAP1
      and Bcl2. These results indicate that AECs possess endogenous mechanisms making
      them highly resistant to apoptosis due to asthma-related inflammatory cytokines,
      and the activity of cIAP2 plays an important role in this protection. 

PMID- 24303190
TI  - Use of the HR index to predict maximal oxygen uptake during different exercise
      protocols.
AB  - This study examined the ability of the HRindex model to accurately predict
      maximal oxygen uptake ([Formula: see text]O2max) across a variety of incremental
      exercise protocols. Ten men completed five incremental protocols to volitional
      exhaustion. Protocols included three treadmill (Bruce, UCLA running, Wellness
      Fitness Initiative [WFI]), one cycle, and one field (shuttle) test. The HRindex
      prediction equation (METs = 6 * HRindex - 5, where HRindex = HRmax/HRrest) was
      used to generate estimates of energy expenditure, which were converted to body
      mass-specific estimates of [Formula: see text]O2max. Estimated [Formula: see
      text]O2max was compared with measured [Formula: see text]O2max. Across all
      protocols, the HRindex model significantly underestimated [Formula: see
      text]O2max by 5.1 mL.kg(-1).min(-1) (95% CI: -7.4, -2.7) and the standard error
      of the estimate (SEE) was 6.7 mL.kg(-1).min(-1). Accuracy of the model was
      protocol-dependent, with [Formula: see text]O2max significantly underestimated
      for the Bruce and WFI protocols but not the UCLA, Cycle, or Shuttle protocols.
      Although no significant differences in [Formula: see text]O2max estimates were
      identified for these three protocols, predictive accuracy among them was not
      high, with root mean squared errors and SEEs ranging from 7.6 to 10.3 mL.kg(
      1).min(-1) and from 4.5 to 8.0 mL.kg(-1).min(-1), respectively. Correlations
      between measured and predicted [Formula: see text]O2max were between 0.27 and
      0.53. Individual prediction errors indicated that prediction accuracy varied
      considerably within protocols and among participants. In conclusion, across
      various protocols the HRindex model significantly underestimated [Formula: see
      text]O2max in a group of aerobically fit young men. Estimates generated using the
      model did not differ from measured [Formula: see text]O2max for three of the five
      protocols studied; nevertheless, some individual prediction errors were large.
      The lack of precision among estimates may limit the utility of the HRindex model;
      however, further investigation to establish the model's predictive accuracy is
      warranted. 

PMID- 24303191
TI  - Obesity decreases excitability of putative ventral tegmental area GABAergic
      neurons.
AB  - Palatable food has reinforcing effects on feeding and accelerates obesity.
      Alteration of food-related behavior in obesity may promote maintenance of
      obesity. The ventral tegmental area (VTA) of the midbrain is important for food
      reward. However, it is unknown whether activity of VTA neurons is altered in diet
      induced obesity. In this study, we examined VTA neuronal activity using an
      electrophysiological technique in diet-induced obese mice. Male 4-week-old mice
      were fed a high-fat diet or a standard diet for 5-6 weeks. Mice fed a high-fat
      diet gained greater body weight with heavier visceral fat compared with those fed
      a standard diet. Brain slice preparations were obtained from the lean and obese
      mice. Spontaneous activity of VTA neurons was recorded extracellularly. We found
      a negative correlation between firing frequency (FF) and action potential (AP)
      current duration in lean and obese mice VTA neurons. VTA neurons were classified
      as group-1 neurons (FF <5.0 Hz and AP current duration >1.2 msec) or group-2
      neurons (FF ?5.0 Hz and AP current duration ?1.2 msec). FF, AP current duration,
      and firing regularity of VTA group-1 neurons were similar between lean and obese
      mice. Obese mice VTA group-2 neurons had a lower FF and shorter AP current
      duration compared with lean mice. In conclusion, obesity minimally affects VTA
      group-1 neurons, which are presumed to be dopaminergic, but decreases
      excitability of VTA group-2 neurons, which are presumed to be GABAergic. This
      differential effect may contribute to the pathophysiology of reward-related
      feeding in obesity. 

PMID- 24303192
TI  - OVLT lesion decreases basal arterial pressure and the chronic hypertensive
      response to AngII in rats on a high-salt diet.
AB  - We have reported that lesion of the organum vasculosum of the lamina terminalis
      (OVLT) has no effect on basal levels of mean arterial pressure (MAP) but
      abolishes the hypertensive effects of angiotensin II (AngII) in rats consuming a
      normal-salt diet. These results suggest that the OVLT does not contribute to
      regulation of MAP under conditions of normal salt intake, but it is an important
      brain site for the hypertensive actions of AngII. The OVLT has been proposed as a
      major sodium sensor in the brain and the hypertensive effects of AngII are
      exacerbated by high-salt intake. Therefore, the objective of this study was to
      investigate the role of the OVLT during AngII-induced hypertension in rats fed a
      high-salt diet. Male Sprague-Dawley rats underwent sham (Sham; n = 9) or OVLT
      lesion (OVLTx; n = 8) surgery and were placed on a high-salt (2% NaCl) diet. MAP
      was measured by radio telemetry during three control days, 10 days of AngII
      infusion (10 ng/kg/min, i.v.), and a 3-day recovery period. MAP was significantly
      lower in OVLTx (97 +/- 2 mmHg) compared to Sham (106 +/- 1 mmHg) rats during the
      control period (P < 0.05). Moreover, the chronic pressor response to AngII was
      markedly attenuated in OVLTx rats. MAP increased 58 +/- 3 mmHg in Sham rats by
      Day 10 of AngII compared to a 40 +/- 7 mmHg increase in OVLTx rats (P < 0.05). We
      conclude that (1) the OVLT regulates the basal levels of MAP in rats consuming a
      high-salt and (2) the OVLT is an important brain site of action for the
      pathogenesis of AngII-salt hypertension in the rat. Supported by HL076312. 

PMID- 24303193
TI  - Reticular activating system of a central pattern generator: premovement
      electrical potentials.
AB  - For the first time, here we characterize a bulbar reticular activating system
      (RAS) of neurons in decerebrate, deafferented and decerebellated cats producing a
      premovement electrical potential that we named obex slow potential (OSP). The OSP
      occurs about 0.8 +/- 0.4 sec prior to the onset of a fictive-scratching-episode.
      Here, we describe two classes of bulbar neurons, off-on, which are silent but
      exhibit a 80 +/- 56 Hz firing discharge at the beginning of (and during) the OSP,
      and on-off interneurons, with a 27 +/- 14 Hz firing activity that stops at the
      beginning of (and during) the OSP. We suggest that these OSP-associated neurons
      belong to a descending RAS, which contributes to the activation of the spinal
      central pattern generators. 

PMID- 24303194
TI  - Total daily energy expenditure is increased following a single bout of sprint
      interval training.
AB  - REGULAR ENDURANCE EXERCISE IS AN EFFECTIVE STRATEGY FOR HEALTHY WEIGHT
      MAINTENANCE, MEDIATED VIA INCREASED TOTAL DAILY ENERGY EXPENDITURE (TDEE), AND
      POSSIBLY AN INCREASE IN RESTING METABOLIC RATE (RMR: the single largest component
      of TDEE). Sprint interval training (SIT) is a low-volume alternative to endurance
      exercise; however, the utility of SIT for healthy weight maintenance is less
      clear. In this regard, it is feasible that SIT may evoke a thermogenic response
      above and beyond the estimates required for prevention of weight gain (i.e., >200
      600 kJ). The purpose of these studies was to investigate the hypotheses that a
      single bout of SIT would increase RMR and/or TDEE. Study 1: RMR (ventilated hood)
      was determined on four separate occasions in 15 healthy men. Measurements were
      performed over two pairs of consecutive mornings; each pair was separated by 7
      days. Immediately following either the first or third RMR measurement (randomly
      assigned) subjects completed a single bout of SIT (cycle ergometer exercise). RMR
      was unaffected by a single bout of SIT (7195 +/- 285 kJ/day vs. 7147 +/- 222,
      7149 +/- 246 and 6987 +/- 245 kJ/day (mean +/- SE); P = 0.12). Study 2: TDEE
      (whole-room calorimeter) was measured in 12 healthy men, on two consecutive days,
      one of which began with a single bout of SIT (random order). Sprint exercise
      increased TDEE in every research participant (9169 +/- 243 vs. 10,111 +/- 260
      kJ/day; P < 0.0001); the magnitude of increase was 946 +/- 62 kJ/day (~10%).
      These data provide support for SIT as a strategy for increasing TDEE, and may
      have implications for healthy body weight maintenance. 

PMID- 24303195
TI  - Development of renal renin-expressing cells does not involve PDGF-B-PDGFR-beta
      signaling.
AB  - Apart from their endocrine functions renin-expressing cells play an important
      functional role as mural cells of the developing preglomerular arteriolar vessel
      tree in the kidney. The recruitment of renin-expressing cells from the mesenchyme
      to the vessel wall is not well understood. Assuming that it may follow more
      general lines of pericyte recruitment to endothelial tubes we have now
      investigated the relevance of the platelet-derived growth factor (PDGF)-B-PDGFR
      beta signaling pathway in this context. We studied renin expression in kidneys
      lacking PDGFR-beta in these cells and in kidneys with reduced endothelial PDGF-B
      expression. We found that expression of renin in the kidneys under normal and
      stimulated conditions was not different from wild-type kidneys. As expected,
      PDGFR-beta immunoreactivity was found in mesangial, adventitial and tubulo
      interstitial cells but not in renin-expressing cells. These findings suggest that
      the PDGF-B-PDGFR-beta signaling pathway is not essential for the recruitment of
      renin-expressing cells to preglomerular vessel walls in the kidney. 

PMID- 24303196
TI  - Metaplastic LTP inhibition after LTD induction in CA1 hippocampal slices involves
      NMDA Receptor-mediated Neurosteroidogenesis.
AB  - Long-term depression (LTD) induced by low-frequency electrical stimulation (LFS)
      in the CA1 region of the hippocampus is a form of synaptic plasticity thought to
      contribute to learning and memory and to the pathophysiology of neuropsychiatric
      disorders. In naive hippocampal slices from juvenile rats, we previously found
      that LTD induction can impair subsequent induction of long-term potentiation
      (LTP) via a form of N-methyl-d-aspartate receptor (NMDAR)-dependent
      metaplasticity, and have recently observed that pharmacologically induced NMDAR
      dependent LTP inhibition involves 5alpha-reduced neurosteroids that augment the
      actions of gamma-aminobutyric acid (GABA). In this study, we found that both LFS
      induced LTD and subsequent inhibition of LTP induction involve neurosteroid
      synthesis via NMDAR activation. Furthermore, the timing of 5alpha-reductase
      inhibition relative to LFS can dissociate effects on LTD and metaplastic LTP
      inhibition. These findings indicate that 5alpha-reduced neurosteroids play an
      important role in synaptic plasticity and synaptic modulation in the hippocampus.

PMID- 24303198
TI  - Bibliometric Indicators of Russian Journals by JCR-Science Edition, 1995-2010.
AB  - A representative empirical bibliometric analysis of Russian journals included in
      the Journal Citation Reports-Science Edition (JCR-SE) for the time period 1995
      2010 was conducted at the macro level (excluding the subject categories). It was
      found that the growth in the number of articles covered by JCR (a 1.8-fold
      increase compared to 1995) is ahead of the growth rates of Russian publications
      (1.2-fold increase). Hence, the share of Russian articles covered by JCR-SE was
      down from 2.5% in 1995 to 1.7% in 2010. It was determined that the number of
      articles published in an average Russian journal reduced by 20% as compared to
      the number of articles in an average journal of the full data set. These facts
      could partly shed light on the question why Russian research performance is
      staggering (approximately 30,000 articles per year), although the coverage of
      Russian journals has expanded to 150 titles. Over the past 15 years, a twofold
      increase in the impact factor of the Russian journals has been observed, which is
      higher than that for the full data set of journals (a 1.4-fold increase).
      Measures to improve the quality of Russian journals are proposed. 

PMID- 24303197
TI  - Analyses of the effects of Gq protein on the activated states of the muscarinic
      M3 receptor and the purinergic P2Y1 receptor.
AB  - G protein-coupled receptors (GPCRs) cause various cellular responses through
      activating heterotrimeric G protein upon the agonist binding. The interaction
      with G protein has been suggested to stabilize the agonist-bound active
      conformation of GPCRs. We previously reported the effects of Gq protein on the
      stabilization of the active conformation of the muscarinic receptor type 1 (M1R),
      using a fluorescence resonance energy transfer (FRET) technique. In this study,
      we aimed at examining whether or not the binding of Gq protein affects the
      agonist-induced active conformation of receptors other than the M1R. For this
      purpose, functionally intact fluorescent receptors of the metabotropic purinergic
      receptor type 1 (P2Y1R) and muscarinic receptor type 3 (M3R) were constructed, by
      inserting junctional linkers between the short intracellular third loops (i3) and
      yellow fluorescent protein (YFP). The YFP-fused receptors also showed the agonist
      induced increases in FRET from the cyan fluorescent protein (CFP) tethered with
      Galphaq subunit, indicating that they interacted with Gq protein. The agonist
      induced conformational changes of the receptors were detected as the agonist
      induced decrease in FRET between YFP at the i3 and CFP at the C-tail. The FRET
      decrease of the M3R but not of the P2Y1R was enhanced by coexpression of Gq
      protein. In addition, coexpression of Gq protein significantly decelerated the
      FRET recovery of the M3R construct but not of the P2Y1R construct upon the
      agonist removal. These results suggest that the effects of the Gq binding on the
      active conformation of the receptor differ depending on the type of GPCRs. 

PMID- 24303199
TI  - Big Data in Biology and Medicine: Based on material from a joint workshop with
      representatives of the international Data-Enabled Life Science Alliance, July 4,
      2013, Moscow, Russia.

PMID- 24303202
TI  - Acadesine Triggers Non-apoptotic Death in Tumor Cells.
AB  - We studied the cytotoxicity of acadesine (5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside) for tumor and normal cells of various species and tissue origin.
      In tumor cells, acadesine triggered non-apoptotic death; the potency of the
      compound to normal cells was substantially lower. Acadesine was toxic for tumor
      cells with multidrug resistant phenotypes caused by the transmembrane transporter
      R-glycoprotein or lack of proapoptotic p53. Activity of adenosine receptors was
      required for acadesine-induced cell death, whereas functioning of AMR-dependent
      protein kinase was not required. A more pronounced cytotoxicity for tumor cells,
      as well as the non-canonical death mechanism(s), makes acadesine a promising
      candidate for antitumor therapy. 

PMID- 24303200
TI  - Modern aspects of the structural and functional organization of the DNA mismatch
      repair system.
AB  - This review is focused on the general aspects of the DNA mismatch repair (MMR)
      process. The key proteins of the DNA mismatch repair system are MutS and MutL. To
      date, their main structural and functional characteristics have been thoroughly
      studied. However, different opinions exist about the initial stages of the
      mismatch repair process with the participation of these proteins. This review
      aims to summarize the data on the relationship between the two MutS functions,
      ATPase and DNA-binding, and to systematize various models of coordination between
      the mismatch site and the strand discrimination site in DNA. To test these
      models, novel techniques for the trapping of short-living complexes that appear
      at different MMR stages are to be developed. 

PMID- 24303203
TI  - Cancer specificity of promoters of the genes involved in cell proliferation
      control.
AB  - Core promoters with adjacent regions of the human genes CDC6, POLD1, CKS1B, MCM2,
      and PLK1 were cloned into a pGL3 vector in front of the Photinus pyrails gene Luc
      in order to study the tumor specificity of the promoters. The cloned promoters
      were compared in their ability to direct luciferase expression in different human
      cancer cells and in normal fibroblasts. The cancer-specific promoter BIRC5 and
      non-specific CMV immediately early gene promoter were used for comparison. All
      cloned promoters were shown to be substantially more active in cancer cells than
      in fibroblasts, while the PLK1 promoter was the most cancer-specific and
      promising one. The specificity of the promoters to cancer cells descended in the
      series PLK1, CKS1B, POLD1, MCM2, and CDC6. The bidirectional activity of the
      cloned CKS1B promoter was demonstrated. It apparently directs the expression of
      the SHC1 gene, which is located in a "head-to-head" position to the CKS1B gene in
      the human genome. This feature should be taken into account in future use of the
      CKS1B promoter. The cloned promoters may be used in artificial genetic
      constructions for cancer gene therapy. 

PMID- 24303204
TI  - Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive
      Functions in Rat Models of Alzheimer's Disease.
AB  - Dipeptide mimetic of the nerve growth factor (NGF) loop 4, hexamethylenediamide
      bis-(N-monosuccinyl- glutamyl-lysine) (GK-2), was synthesized at the V.V. Zakusov
      Scientific Research Institute of Pharmacology of the Russian Academy of Medical
      Sciences. GK-2 exhibited in vitro neuroprotective activity at nanomolar
      concentrations, was efficient in animal models of the Parkinson's disease,
      ischemic and hemorrhagic stroke, and global cerebral ischemia at doses of 0.01-5
      mg/kg (intraperitoneally) and 10 mg/kg (per os). The mnemotropic effects of
      subchronic intraperitoneal administration of GK-2 on rat models of the
      Alzheimer's disease are described in this paper. Dipeptide GK-2 at a dose of 1
      mg/kg is found to decrease the habituation deficit induced by the septo
      hippocampal pathway transsection and, at a dose of 0.5 mg/kg, to significantly
      prevent spatial memory impairment in Morris water maze induced by intracerebral
      injection of streptozotocin. Thus, GK-2, an original dipeptide mimetic of NGF,
      acts on models of the Alzheimer's disease upon systemic administration. 

PMID- 24303201
TI  - Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs.
AB  - RNA interference (RNAi) is a powerful method used for gene expression regulation.
      The increasing knowledge about the molecular mechanism of this phenomenon creates
      new avenues for the application of the RNAi technology in the treatment of
      various human diseases. However, delivery of RNA interference mediators, small
      interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe
      pharmacological use of siRNAs requires carriers that can deliver siRNA to its
      target site and the development of methods for protection of these fragile
      molecules from in vivo degradation. This review summarizes various strategies for
      siRNA delivery, including chemical modification and non-viral approaches, such as
      the polymer-based, peptide-based, lipid-based techniques, and inorganic
      nanosystems. The advantages, disadvantages, and prospects for the therapeutic
      application of these methods are also examined in this paper. 

PMID- 24303205
TI  - Kinetic Parameters and Cytotoxic Activity of Recombinant Methionine gamma-Lyase
      from Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis and
      Citrobacter freundii.
AB  - The steady-state kinetic parameters of pyridoxal 5'-phosphate-dependent
      recombinant methionine gamma -lyase from three pathogenic bacteria, Clostridium
      tetani, Clostridium sporogenes, and Porphyromonas gingivalis, were determined in
      beta- and gamma-elimination reactions. The enzyme from C. sporogenes is
      characterized by the highest catalytic efficiency in the gamma-elimination
      reaction of L-methionine. It was demonstrated that the enzyme from these three
      sources exists as a tetramer. The N-terminal poly-histidine fragment of three
      recombinant enzymes influences their catalytic activity and facilitates the
      aggregation of monomers to yield dimeric forms under denaturing conditions. The
      cytotoxicity of methionine gamma-lyase from C. sporogenes and C. tetani in
      comparison with Citrobacter freundii was evaluated using K562, PC-3, LnCap, MCF7,
      SKOV-3, and L5178y tumor cell lines. K562 (IC50=0.4-1.3 U/ml), PC-3 (IC50=0.1-0.4
      U/ml), and MCF7 (IC50=0.04-3.2 U/ml) turned out to be the most sensitive cell
      lines. 

PMID- 24303206
TI  - The Impact of ADH1B Alleles and Educational Status on Levels and Modes of Alcohol
      Consumption in Russian Male Individuals.
AB  - Alcohol abuse is one of the main reasons behind the low life span in Russia. Both
      social and genetic factors affect the alcohol consumption level. The genetic
      factors are alleles of the alcohol dehydrogenase ADH1B and aldehyde
      dehydrogenaseALDH2 genes. We have typed and found frequencies for the alleles in
      a cohort of 642 men, ethnic Russians. The individuals of the cohort were asked to
      complete a questionnaire in the framework of the Izhevsk Family Study (Leon et
      al., 2007, 2009) regarding the amount of alcohol consumed and on the type of
      hazardous alcohol consumption (nonbeverage alcohol consumption and the so-called
      "zapoi" which is a Russian term for a heavy drinking bout lasting for at least 2
      days, when an individual is withdrawn from the normal social life). The
      ADH1B*48His allele was found among heterozygous individuals only (N=68, 10.6% of
      the cohort). The ALDH2*504Lys allele was also found among heterozygous
      individuals only (N=2, 0.3%) The effect of ADH1B alleles and the influence of the
      education level on the amount and type of alcohol consumed had not previously
      been studied in Russians. We have found that the amount of consumed alcohol is
      21.6% lower (1733 g of ethanol per year) for ADH1B*48His allele carriers in the
      cohort of Russian men. The amount of consumed alcohol was found to be 9.8% lower
      (793 g of ethanol per year) in the case when individuals had a higher education
      as compared to those who had a secondary- or elementary school education level in
      the same cohort. Hence, the protective effect of the genetic factor (ADH1B*48His
      allele carriage) has proven to be more pronounced than the influence of the
      social factor (education level) at the individual level in the cohort of Russian
      men. Both factors have also proven to have a protective effect against hazardous
      types of alcohol consumption. Zapoi was not scored among individuals of the
      cohort with ADH1B*48His allele carriage (OR=12.6, P=0.006), as compared to 8.4%
      of "zapoi" individuals who did not carry the ADH1B*48His allele (genotype
      Arg/Arg).The percentage of individuals who consume non-beverage alcohol is lower
      (0.6%) in the subcohort of people with a higher education degree. This percentage
      is higher (6.0%, OR=10.0, P=0.004) in the subcohort of people without a higher
      education degree. 

PMID- 24303208
TI  - Stabilization of the Central Part of Tropomyosin Molecule Alters the Ca2+
      sensitivity of Actin-Myosin Interaction.
AB  - We show that the mutations D137L and G126R, which stabilize the central part of
      the tropomyosin (Tm) molecule, increase both the maximal sliding velocity of the
      regulated actin filaments in the in vitro motility assay at high Sa(2+)
      concentrations and the Sa(2+)-sensitivity of the actin-myosin interaction
      underlying this sliding. Based on an analysis of the recently published data on
      the structure of the actin-Tm-myosin complex, we suppose that the physiological
      effects of these mutations in Tm can be accounted for by their influence on the
      interactions between the central part of Tm and certain sites of the myosin head.

PMID- 24303207
TI  - Metagenomic Analysis of the Dynamic Changes in the Gut Microbiome of the
      Participants of the MARS-500 Experiment, Simulating Long Term Space Flight.
AB  - A metagenomic analysis of the dynamic changes of the composition of the
      intestinal microbiome of five participants of the MARS-500 experiment was
      performed. DNA samples were isolated from the feces of the participants taken
      just before the experiment, upon 14, 30, 210, 363 and 510 days of isolation in
      the experimental module, and two weeks upon completion of the experiment. The
      taxonomic composition of the microbiome was analyzed by pyrosequencing of 16S
      rRNA gene fragments. Both the taxonomic and functional gene content of the
      microbiome of one participant were analyzed by whole metagenome sequencing using
      the SOLiD technique. Each participant had a specific microbiome that could be
      assigned to one of three recognized enterotypes. Two participants had enterotype
      I microbiomes characterized by the prevalence of Bacteroides, while the
      microbiomes of two others, assigned to type II, were dominated by Prevotella. One
      participant had a microbiome of mixed type. It was found that (1) changes in the
      taxonimic composition of the microbiomes occurred in the course of the
      experiment, but the enterotypes remained the same; (2) significant changes in the
      compositions of the microbiomes occurred just 14-30 days after the beginning of
      the experiment, presumably indicating the influence of stress factors in the
      first stage of the experiment; (3) a tendency toward a reversion of the
      microbiomes to their initial composition was observed two weeks after the end of
      the experiment, but complete recovery was not achieved. The metagenomic analysis
      of the microbiome of one of the participants showed that in spite of variations
      in the taxonomic compositions of microbiomes, the "functional" genetic
      composition was much more stable for most of the functional gene categories.
      Probably in the course of the experiment the taxonomic composition of the gut
      microbiome was adaptively changed to reflect the individual response to the
      experimental conditions. A new, balanced taxonomic composition of the microbiome
      was formed to ensure a stable gene content of the community as a whole without
      negative consequences for the health of the participants. 

PMID- 24303209
TI  - Vacuum-assisted continuous circular capsulorhexis using bimanual irrigation and
      aspiration system of phaco machine in immature cataract.
AB  - Seventy-eight eye of 65 patients were enrolled in this retrospective clinical
      study. Two-side ports are made with a 23-gauge stiletto knife. The irrigation
      handpiece is introduced into the anterior chamber through one side port and 27
      gauge cystotome is introduced through the other one. Anterior capsular flap is
      created with cystotome. The capsular flap is vacuumed with a 25-gauge visco
      elastic's cannula, which connected to the phaco machine vacuum. The continuous
      circular capsulorhexis (CCC) is completed with the using bimanual irrigation and
      aspiration system of phaco machine. Vacuum-assisted CCC technique was used in 78
      cases of uncomplicated immature senile cataracts. All cases were done under sub
      Tenon's anesthesia. A complete CCC was achieved in all cases. Performing CCC with
      our technique is easy, safe, and cheap. It may be an alternative method to CCC by
      using OVD and forceps. 

PMID- 24303211
TI  - Job Satisfaction and Burnout among Intensive Care Unit Nurses and Physicians.
AB  - Introduction. Nurses and physicians working in the intensive care unit (ICU) may
      be exposed to considerable job stress. The study aim was to assess the level of
      and the relationship between (1) job satisfaction, (2) job stress, and (3)
      burnout symptoms. Methods. A cross-sectional study was performed at ICUs at Oslo
      University Hospital. 145 of 196 (74%) staff members (16 physicians and 129
      nurses) answered the questionnaire. The following tools were used: job
      satisfaction scale (scores 10-70), modified Cooper's job stress questionnaire
      (scores 1-5), and Maslach burnout inventory (scores 1-5); high score in the
      dimension emotional exhaustion (EE) indicates burnout. Personality was measured
      with the basic character inventory. Dimensions were neuroticism (vulnerability),
      extroversion (intensity), and control/compulsiveness with the range 0-9. Results.
      Mean job satisfaction among nurses was 43.9 (42.4-45.4) versus 51.1 (45.3-56.9)
      among physicians, P < 0.05. The mean burnout value (EE) was 2.3 (95% CI 2.2-2.4),
      and mean job stress was 2.6 (2.5-2.7), not significantly different between nurses
      and physicians. Females scored higher than males on vulnerability, 3.3 (2.9-3.7)
      versus 2.0 (1.1-2.9) (P < 0.05), and experienced staff were less vulnerable, 2.7
      (2.2-3.2), than inexperienced staff, 3.6 (3.0-4.2) (P < 0.05). Burnout (EE)
      correlated with job satisfaction (r = -0.4, P < 0.001), job stress (r = 0.6, P <
      0.001), and vulnerability (r = 0.3, P = 0.003). Conclusions. The nurses were
      significantly less satisfied with their jobs compared to the physicians. Burnout
      mean scores are relatively low, but high burnout scores are correlated with
      vulnerable personality, low job satisfaction, and high degree of job stress. 

PMID- 24303210
TI  - Effects of Roux-en-Y gastric bypass on fasting and postprandial levels of the
      inflammatory markers YKL-40 and MCP-1 in patients with type 2 diabetes and
      glucose tolerant subjects.
AB  - BACKGROUND: The inflammatory markers YKL-40 and monocyte chemoattractant protein
      1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss.
      The objective of our study was to investigate the possible changes of YKL-40 and
      MCP-1, in both the fasting and the postprandial states, following Roux-en-Y
      gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose
      tolerance (NGT). METHODS: Ten obese patients with T2D and 10 subjects with NGT
      were examined in the fasting state and after a standard meal prior to and after
      (1 week, 3 months, and 1 year) RYGB. RESULTS: Fasting state MCP-1 levels
      decreased after RYGB in both groups (P values < 0.0001) whereas fasting YKL-40
      levels were unchanged (P values >= 0.120). Postprandial MCP-1 levels showed a
      tendency towards a decrease on most study days; however, the changes were only
      significant at 1 week (P = 0.001) and 1 yr (P < 0.0001) in the T2D group and at 3
      mo after RYGB in the NGT group (P = 0.009). YKL-40 levels showed a slight,
      postprandial suppression on all study days in the T2D group (all P values <=
      0.021). CONCLUSIONS: Fasting MCP-1 levels, but not YKL-40 levels, decrease after
      RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers
      are discrete and inconsistent.

PMID- 24303212
TI  - Attitudes toward Genetic Testing for Hypertension among African American Women
      and Girls.
AB  - Introduction. Although African American (AA) women have the highest prevalence of
      hypertension and many genetic studies have been conducted to examine this
      disparity, no published studies have investigated their attitudes toward genetic
      testing for hypertension. The purpose of the present study was to use the health
      belief model as a guide to examine attitudes toward perceived barriers and
      benefits of genetic testing held by AA multigenerational triads and to determine
      whether they differed by generation, age, education, or income level. Methods. A
      descriptive correlational research design were used with 183 African American
      women and girls from Detroit. Correlations between triad membership, age, income,
      and education level were examined for association with attitudes toward genetic
      testing. Results. Increasing age and education were associated with significant
      differences in attitudes regarding benefits (F[2, 160] = 5.19, P = 0.007, d =
      0.06) and awareness (F[2, 160] = 6.49, P = 0.002, d = 0.08). No statistically
      significant differences existed on the three subscales when compared by income
      levels or triad membership. Conclusions. This highlights the need for increased
      outreach to younger generations regarding benefits of genetic services. Further
      research is necessary to determine whether rural and male populations have
      similar beliefs. 

PMID- 24303213
TI  - Public Health Nursing in the 21st Century: Challenges and Opportunities for Women
      and Children's Health.

PMID- 24303214
TI  - Anticoagulation for prosthetic valves.
AB  - Implantation of prosthetic valve requires consideration for anticoagulation. The
      current guideline recommends warfarin on all mechanical valves. Dabigatran is the
      new generation anticoagulation medication which is taken orally and does not
      require frequent monitoring. This drug is approved for treatment for atrial
      fibrillation and venous thromboembolism, but the latest large trial showed that
      this drug increases adverse events when used for mechanical valve
      anticoagulation. On-X valve is the new generation mechanical valve which is
      considered to require less anticoagulation due to its flow dynamics. The latest
      study showed that lower anticoagulation level lowers the incidence of bleeding,
      while the risk of thromboembolism and thrombosis remained the same.
      Anticoagulation poses dilemma in cases such as pregnancy and major bleeding
      event. During pregnancy, warfarin can be continued throughout pregnancy and
      switched to heparin derivative during 6-12 weeks and >36 weeks of gestation.
      Warfarin can be safely started after 1-2 weeks of discontinuation following major
      bleeding episode. 

PMID- 24303215
TI  - Plasma amino acids changes in complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) is a severe chronic pain condition that
      most often develops following trauma. Blood samples were collected from 220
      individuals, 160 CRPS subjects, and 60 healthy pain-free controls. Plasma amino
      acid levels were compared and contrasted between groups. L-Aspartate, L
      glutamate, and L-ornithine were significantly increased, whereas L-tryptophan and
      L-arginine were significantly decreased in CRPS subjects as compared to controls.
      In addition, the L-kynurenine to L-tryptophan ratio demonstrated a significant
      increase, whereas the global arginine bioavailability ratio (GABR) was
      significantly decreased in the CRPS subjects. The CRPS subjects demonstrated a
      significant correlation between overall pain and the plasma levels of L-glutamate
      and the L-kynurenine to L-tryptophan ratio. CRPS subjects also showed a
      correlation between the decrease in plasma L-tryptophan and disease duration.
      This study shows that CRPS subjects exhibit significant changes in plasma levels
      of amino acids involved in glutamate receptor activation and in amino acids
      associated with immune function as compared to healthy pain-free controls. A
      better understanding of the role plasma amino acids play in the pathophysiology
      of CRPS may lead to novel treatments for this crippling condition. 

PMID- 24303216
TI  - Insight, neurocognition, and schizophrenia: predictive value of the wisconsin
      card sorting test.
AB  - Lack of insight in schizophrenia is a key feature of the illness and is
      associated with both positive and negative clinical outcomes. Previous research
      supports that neurocognitive dysfunction is related to lack of insight, but
      studies have not examined how neurocognition relates to change in insight over
      time. Therefore, the current study sought to understand how performance on the
      Wisconsin Card Sorting Test (WCST) differed between participants with varying
      degrees of change in insight over a 6-month period. Fifty-two patients with
      schizophrenia or schizoaffective disorder were administered the WCST and Positive
      and Negative Syndrome Scale (PANSS) at baseline, and the PANSS was again
      administered at a 6-month follow-up assessment. Results indicated that while
      neurocognition was related to insight at baseline, it was not related to
      subsequent change in insight. The implications of findings for conceptualization
      and assessment of insight are discussed. 

PMID- 24303217
TI  - Social Support Contributes to Outcomes following Distal Radius Fractures.
AB  - Background. Distal radius fractures are the most common fracture of the upper
      extremity and cause variable disability. This study examined the role of social
      support in patient-reported pain and disability at one year following distal
      radius fracture. Methods. The Medical Outcomes Study Social Support Survey was
      administered to a prospective cohort of 291 subjects with distal radius fractures
      at their baseline visit. Pearson correlations and stepwise linear regression
      models (F-to-remove 0.10) were used to identify whether social support
      contributes to wrist fracture outcomes. The primary outcome of pain and
      disability at one year was measured using the Patient Rated Wrist Evaluation.
      Results. Most injuries were low energy (67.5%) and were treated nonoperatively
      (71.9%). Pearson correlation analysis revealed that higher reported social
      support correlated with improved Patient Rated Wrist Evaluation scores at 1 year,
      r(n = 181) = -0.22, P < 0.05. Of the subscales within the Social Support Survey,
      emotional/informational support explained a significant proportion of the
      variance in 1-year Patient Rated Wrist Evaluation scores, R (2) = 4.7%, F (1,
      181) = 9.98, P < 0.05. Conclusion. Lower emotional/informational social support
      at the time of distal radius fracture contributes a small but significant
      percentage to patient-reported pain and disability outcomes. 

PMID- 24303219
TI  - Genetic mapping in papillon-lefevre syndrome: a report of two cases.
AB  - Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive heterogeneous trait
      which is characterized by erythematous palmoplantar hyperkeratosis, early-onset
      periodontitis, and associated calcification of dura mater. The etiology of PLS is
      multifactorial with genetic, immunological, and microbial factors playing a role
      in etiopathogenesis. Recently identified genetic defect in PLS has been mapped to
      chromosome 11q14-q21, which involves mutations of cathepsin C. This paper
      presents a report of 2 cases of Papillon-lefevre syndrome in which diagnosis is
      based on clinical presentation and genetic mapping. 

PMID- 24303220
TI  - A case report of mycobacterium avium complex peritonitis in an AIDS patient.
AB  - Peritonitis due to Mycobacterium avium complex (MAC) infection is uncommon. The
      risk for MAC in AIDS patients is greatest in those with severely depressed CD4
      count. The organs most commonly involved in disseminated MAC infection include
      spleen, mesenteric lymph nodes, liver, and intestines. The involvement of
      peritoneum by MAC infection is rare. This is a case of MAC peritonitis in a 26
      year-old female AIDS patient who is noncompliant to highly active antiretroviral
      therapy (HAART). This patient presented with abdominal pain and distension,
      anorexia, diarrhea, and cough. She was treated with rifabutin, clarithromycin,
      and ethambutol along with atovaquone for Pneumocystis jiroveci pneumonia
      prophylaxis and so the patient's condition improved. MAC peritonitis should be
      considered in a patient presenting with nonspecific abdominal symptoms in the
      setting of AIDS and low CD4 count. 

PMID- 24303218
TI  - Microglia: an active player in the regulation of synaptic activity.
AB  - Synaptic plasticity is critical for elaboration and adaptation in the developing
      and developed brain. It is well established that astrocytes play an important
      role in the maintenance of what has been dubbed "the tripartite synapse".
      Increasing evidence shows that a fourth cell type, microglia, is critical to this
      maintenance as well. Microglia are the resident macrophages of the central
      nervous system (CNS). Because of their well-characterized inflammatory functions,
      research has primarily focused on their innate immune properties. The role of
      microglia in the maintenance of synapses in development and in homeostasis is not
      as well defined. A number of significant findings have shed light on the critical
      role of microglia at the synapse. It is becoming increasingly clear that
      microglia play a seminal role in proper synaptic development and elimination. 

PMID- 24303221
TI  - Mucoepidermoid carcinoma of the lung: a case report and literature review.
AB  - Introduction. Mucoepidermoid carcinoma (MEC) of the lung is a rare form of lung
      cancer that is classified into low grade and high grade based on histological
      features. Surgical resection is the primary treatment for low-grade MEC with
      excellent outcomes, while high-grade MEC is a more aggressive form of malignancy.
      Clinical Case. We report a case of a 46-year-old woman who presented with dyspnea
      on exertion. Imaging studies revealed a mass involving the right upper lobe
      bronchus. Bronchoscopy, surgical resection, and pathological examination revealed
      a low-grade MEC with tumor-free margins. No adjuvant treatment was given.
      Discussion. Primary pulmonary MEC is a rare type of lung cancer with only few
      reported cases. This patient illustrates a typical presentation for low-grade MEC
      wherein surgical resection is considered curative. In contrast, high-grade MEC is
      a more aggressive malignancy with a poorer outcome. The role of targeted therapy
      directed against EGFR or a novel CRTC1-MAML2 fusion protein expressed in some
      high-grade tumors is yet to be determined. 

PMID- 24303222
TI  - Retroperitoneal angiomyolipoma: a case report and review of the literature.
AB  - Retroperitoneal angiomyolipoma is a rare tumour that is difficult to diagnose
      preoperatively. We present a case of retroperitoneal angiomyolipoma that
      highlights its diagnostic dilemma. We also performed a literature review and
      present a review of retroperitoneal angiomyolipoma. 

PMID- 24303223
TI  - Still's Disease in a Pediatric Patient after Liver Transplantation.
AB  - Still's disease (SD) is a multisystemic inflammatory disease characterized by
      persistent arthritis and in many cases with fever of unknown origin. Diagnosis of
      SD is challenging because of nonspecific characteristics and especially in the
      case of a patient with solid organ transplantation and immunosuppressive therapy
      where multiple causes of fever are possible. There is no diagnostic test for SD,
      even though some useful diagnostic criteria or laboratory findings, such as serum
      ferritin levels, have been proposed, and useful imaging studies for the diagnosis
      or followup of SD have not been developed. We report the case of a 9-year-old
      child who presented with high grade fever associated with joint pain after a
      history of liver transplantation and immunosuppressive therapy. Laboratory tests
      showed increased acute phase reactants, elevated ferritin, and leukocytosis. An
      18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed
      identifying abnormal hypermetabolic areas localized in spleen, transplanted
      liver, and bone marrow secondary to inflammatory process. All infectious,
      autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed
      and a steroid-based regimen was initiated with adequate response and no evidence
      of recurrence. To our knowledge this is the first case of SD following a solid
      organ transplant. 

PMID- 24303224
TI  - Adrenal lymphangioma mimicking renal cyst: a case report and review of the
      literature.
AB  - We present a case of a 44-year-old female who was evaluated for left recurrent
      flank and abdominal pain. Abdominal ultrasonography demonstrated a large cystic
      mass on the upper pole of the left kidney. Magnetic resonance imaging showed a
      large, homogenous cystic mass measuring 8.5 * 9.5 cm with well-defined contours,
      being hypointense on T1-weighted images and hyperintense on T2-weighted images on
      the upper pole of the left kidney without a distinct plan between adrenal gland.
      According to clinical and radiological findings, surgical excision was carried
      out with a subcostal flank incision. Histologic and immunohistochemical
      examination demonstrates that the definite diagnosis is cystic lymphangioma of
      the left adrenal gland. Adrenal lymphangioma is a very rare lesion. This is the
      unique case of an adrenal lymphangioma considered as a renal cyst because of its
      radiological appearance. 

PMID- 24303225
TI  - Aortic dissection occurring 18 months after successful endovascular repair in an
      anatomically difficult case of abdominal aortic aneurysm.
AB  - We report an autopsy case of aneurysm dissection that occurred 18 months after
      the implantation of a Zenith stent graft. A 94-year-old woman, who had undergone
      an endovascular repair with postoperative reintervention, died of shock due to
      retroperitoneal hematoma. An autopsy indicated that the stent graft remained
      firmly fixed to the native aorta, whereas the dissection occurred near the
      proximal edge of the stent graft but not at the point of attachment between the
      suprarenal stent hook and the aorta. The luminal surface of the stent graft was
      almost completely covered with a transparent film with an endothelial cell
      lining, which might reflect the tissue regeneration observed on histological
      examination. This was a rare case of acute aortic dissection that occurred 18
      months after EVAR, in which the autopsy indicated interesting microscopic
      findings and the mechanisms underlying the aortic dissection. We believe that
      aggressive reintervention at the proximal site in elderly women might cause the
      dissection of the native aorta. 

PMID- 24303227
TI  - Distributed Health Outcome Monitoring and Evaluation Using i2b2.
AB  - There is a pressing need for better tools to support comparative effectiveness
      research (CER) on a national scale. In addition, little is known about within
      class outcome disparities for commonly used cardiovascular and diabetes
      medications. In this presentation, we will describe our experience implementing a
      new i2b2 cell, the Health Outcome Monitoring and Evaluation Cell (HOME), at 5
      collaborating Clinical Translational Science Award sites (CTSAs) in the U.S. We
      will also describe the motivations to developing a common query framework, and
      findings related to the implementation and use of the HOME cell, to perform
      distributed CER queries. Our focus is on the assessment of race, gender, and
      location-based disparities in outcomes for patients treated with similar
      mediations for hypertension, dyslipidemias, and diabetes. 

PMID- 24303226
TI  - Predictors of cognitive decline in the early stages of Parkinson's disease: a
      brief cognitive assessment longitudinal study.
AB  - Our objectives were to perform a longitudinal assessment of mental status in
      early stage Parkinson's disease (PD) patients, with brief neuropsychological
      tests, in order to find predictive factors for cognitive decline. Sixty-one,
      early stage, and nondemented patients were assessed twice, over a 2-year
      interval, with a global cognitive test (mini-mental state examination (MMSE)) and
      a frontal function test (frontal assessment battery (FAB)) and motor function
      scales. Dementia and hallucinations were diagnosed according to the DSM-IV
      criteria. Cognitive function scores did not decrease significantly, except for
      FAB lexical fluency score. Four patients presented with dementia at followup. The
      MMSE score below cut-off, worse gait dysfunction, the nontremor motor subtype,
      and hallucinations were significantly related to dementia. Rigidity and speech
      dysfunction were related to dementia and a decrease in FAB scores. We can
      conclude that decline in the MMSE and FAB scores is small and heterogeneous in
      the early stages of PD. Scores below cut-off in the MMSE could be helpful to
      predict dementia. Nontremor motor deficits could be predictive factors for
      frontal cognitive decline and dementia. 

PMID- 24303228
TI  - Phenotype Information Retrieval for Existing GWAS Studies.
AB  - The database of Genotypes and Phenotypes (dbGaP) is archiving the results of
      different Genome Wide Association Studies (GWAS). dbGaP has a multitude of
      phenotype variables, but they are not harmonized across studies. We proposed a
      method to standardize phenotype variables by classifying similar variables based
      on semantic distances. We first extracted variables description, enriched them
      using domain knowledge, and computed the distances among them. We used clustering
      techniques to classify the most similar variables. We used domain experts to
      audit clusters, annotated the clusters with appropriate labels, and used re
      clustering to build a semantically-driven Genotypes and Phenotypes (sdGaP)
      ontology using the UMLS semantic network and metathesaurus. The sdGaP ontology
      allowed us to expand user queries and retrieve information using a semantic
      metric called density measure (DM). We illustrated the potential improvement of
      information retrieval using the sdGaP ontology in one search scenario using the
      variables from the Cleveland Family Study. 

PMID- 24303229
TI  - Network analysis of unstructured EHR data for clinical research.
AB  - In biomedical research, network analysis provides a conceptual framework for
      interpreting data from high-throughput experiments. For example, protein-protein
      interaction networks have been successfully used to identify candidate disease
      genes. Recently, advances in clinical text processing and the increasing
      availability of clinical data have enabled analogous analyses on data from
      electronic medical records. We constructed networks of diseases, drugs, medical
      devices and procedures using concepts recognized in clinical notes from the
      Stanford clinical data warehouse. We demonstrate the use of the resulting
      networks for clinical research informatics in two ways-cohort construction and
      outcomes analysis-by examining the safety of cilostazol in peripheral artery
      disease patients as a use case. We show that the network-based approaches can be
      used for constructing patient cohorts as well as for analyzing differences in
      outcomes by comparing with standard methods, and discuss the advantages offered
      by network-based approaches. 

PMID- 24303230
TI  - Towards understanding craniofacial abnormalities: the ontology of craniofacial
      development and malformation.
AB  - We introduce the Ontology of Craniofacial Development and Malformation (OCDM), a
      project of the NIH-funded FaceBase consortium, whose goal is to gather data from
      multiple species, at levels ranging from genes to gross anatomy, in order to
      understand the causes of craniofacial abnormalities. The OCDM is being developed
      in order to facilitate integration of these diverse forms of data in a central
      Hub. It currently consists of several components, including human adult and
      developmental anatomy, corresponding mouse structures, and malformations. Example
      queries show the potential of the OCDM for intelligent data annotation and
      querying. 

PMID- 24303231
TI  - Redactable and auditable data access for bioinformatics research.
AB  - Presently, the process of extraction and dissemination of data subsets for
      research from clinical data warehouses is cumbersome and error prone.
      Furthermore, large-scale research projects often involve multiple users of the
      same data extract; each of these users may be authorized to access different data
      elements and specific subsets of the data extract. Once initial data extraction
      has been done for a research project, capability to transform the data for
      individual users and track which data are being accessed by which users in a
      secure environment is lacking in existing systems. This paper describes several
      methods that the authors are integrating into a system designed to provide
      secure, flexible, and auditable support for supplying users with data subsets.
      The methods implement secure, redactable, and auditable mechanisms for data
      extraction and dissemination. This paper describes the architecture along with an
      initial proof-of-concept implementation. Preliminary performance measurements
      show that the approach manages clinical data in redactable and auditable form
      with reasonable overheads. 

PMID- 24303232
TI  - Mining for clinical expertise in (undocumented) order sets to power an order
      suggestion system.
AB  - Physician orders, the concrete manifestation of clinical decision making, are
      enhanced by the distribution of clinical expertise in the form of order sets and
      corollary orders. Conventional order sets are top-down distributed by committees
      of experts, limited by the cost of manual development, maintenance, and limited
      end-user awareness. An alternative explored here applies statistical data-mining
      to physician order data (>330K order instances from >1.4K inpatient encounters)
      to extract clinical expertise from the bottom-up. This powers a corollary order
      suggestion engine using techniques analogous to commercial product recommendation
      systems (e.g., Amazon.com's "Customers who bought this..." feature). Compared to
      a simple benchmark, the item-based association method illustrated here improves
      order prediction precision from 13% to 18% and further to 28% by incorporating
      information on the temporal relationship between orders. Incorporating statistics
      on conditional order frequency ratios further refines recommendations beyond just
      "common" orders to those relevant to a specific clinical context. 

PMID- 24303233
TI  - Tools for Identifying Reliable Evidence and Implementing it in Everyday Clinical
      Care.
AB  - Just as translational medicine follows a long winding path from bench-to-bedside,
      so can Evidence-Based Medicine be envisioned as comprising a multi-step pipeline,
      from building evidence from raw data through synthesizing best practices and
      providing clinical decision support in a process described as the "evidence
      pyramid". 1 At one end, a heterogeneous mix of clinical and experimental studies
      including clinical trials, case reports, animal models and retrospective analyses
      are published as new knowledge. Then, experts collect and assess high-quality
      relevant evidence on specific issues and publish their conclusions (e.g.,
      regarding efficacy and safety of treatments) as systematic reviews and meta
      analyses. Finally, when an expert consensus has been reached, this must reach the
      attention of policy makers within the profession, the government and insurance
      companies, resulting in new practice guidelines and altered clinical practice
      within hospitals and clinics. At each stage, this process requires a large
      investment of time and effort from many individuals with a wide range of
      expertise. Our panel will discuss the variety of innovative approaches that are
      being taken by different informatics research groups to improve each step within
      the evidence based medicine pipeline. These approaches are, in part, devoted to
      making existing data collection and synthesis practices faster and more
      efficient, but they also involve re-imagining and re-engineering the processes by
      which evidence is accumulated, evaluated and applied. 

PMID- 24303234
TI  - Standard-based integration profiles for clinical research and patient safety.
AB  - EHRs can now be adapted to integrate seamlessly with existing research platforms.
      However, key challenges need to be overcome in order to provide a platform that
      functions across many EHR systems. The IHE Quality, Research and Public Health
      (QRPH) domain addresses the information exchange standards necessary to share
      information relevant to quality improvement in patient care and clinical
      research. In collaboration with CDISC's Healthcare Link initiative, IHE QRPH has
      developed a set of integration profiles that specifically address EHR-enabled
      research. The panel participants from three European projects will present how
      subsets of existing IHE QRPH profiles can be pulled together (and extended when
      necessary) to form a super profile which will standardize and automate the
      clinical trial process flow. The EHR4CR project is providing adaptable, reusable
      and scalable tools and services for reusing data from hospital EHRs for Clinical
      Research. TRANSFoRm is developing an informatics infrastructure to support the
      learning healthcare system in European Primary Care. SALUS project is providing
      scalable, standard based interoperability framework for sustainable proactive
      post market safety studies. Overall, the panel will discuss the key steps towards
      realizing a joint EHR4CR/TRANSFoRm/SALUS European projectathon demonstrating EHR
      enabled clinical research across Europe using standard-based integration and
      content profiles. 

PMID- 24303235
TI  - Leverage hadoop framework for large scale clinical informatics applications.
AB  - In this manuscript, we present our experiences using the Apache Hadoop framework
      for high data volume and computationally intensive applications, and discuss some
      best practice guidelines in a clinical informatics setting. There are three main
      aspects in our approach: (a) process and integrate diverse, heterogeneous data
      sources using standard Hadoop programming tools and customized MapReduce
      programs; (b) after fine-grained aggregate results are obtained, perform data
      analysis using the Mahout data mining library; (c) leverage the column oriented
      features in HBase for patient centric modeling and complex temporal reasoning.
      This framework provides a scalable solution to meet the rapidly increasing,
      imperative "Big Data" needs of clinical and translational research. The intrinsic
      advantage of fault tolerance, high availability and scalability of Hadoop
      platform makes these applications readily deployable at the enterprise level
      cluster environment. 

PMID- 24303236
TI  - Integrating Governance of Research Informatics and Health Care IT Across an
      Enterprise: Experiences from the Trenches.
AB  - Advances in health information technology and biomedical informatics have laid
      the groundwork for significant improvements in healthcare and biomedical
      research. For instance, Electronic Health Records can help improve the delivery
      of evidence-based care, enhance quality, and contribute to discoveries and
      evidence generation. Despite this promise, there are many challenges to achieving
      the vision and missions of our healthcare and research enterprises. Given the
      challenges inherent in doing so, institutions are increasingly moving to
      establish dedicated leadership and governance models charged with designing,
      deploying and leveraging various information resources to advance research and
      advanced care activities at AHCs. Some institutions have even created a new
      leadership position to oversee such activities, such as the Chief Research
      Information Officer. This panel will include research informatics leaders
      discussing their experiences from the proverbial trenches as they work to
      operationalize such cross-mission governance models. Panelists will start by
      providing an overview their respective positions and environments, discuss their
      experiences, and share lessons learned through their work at the intersection of
      clinical and translational research informatics and Health IT. 

PMID- 24303237
TI  - Extracting Computational and Semantic Features from Portable Chest X-rays for
      Diagnosis of Acute Respiratory Distress Syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung disease
      with high mortality risk. Development of new and effective therapies for ARDS has
      been slow due to a lack of precision in its diagnostic criteria. We report
      preliminary research to extract computational and semantic features directly from
      chest X-ray images that are used to train machine learning classifiers. Our
      approach demonstrates the feasibility of using machine learning to identify
      radiographic criteria that are more consistent and accurate for the diagnosis of
      ARDS. 

PMID- 24303238
TI  - "Sitting on pins and needles": characterization of symptom descriptions in
      clinical notes".
AB  - Patients report their symptoms and subjective experiences in their own words.
      These expressions may be clinically meaningful yet are difficult to capture using
      automated methods. We annotated subjective symptom expressions in 750 clinical
      notes from the Veterans Affairs EHR. Within each document, subjective symptom
      expressions were compared to mentions of symptoms in clinical terms and to the
      assigned ICD-9-CM codes for the encounter. A total of 543 subjective symptom
      expressions were identified, of which 66.5% were categorized as mental/behavioral
      experiences and 33.5% somatic experiences. Only two subjective expressions were
      coded using ICD-9-CM. Subjective expressions were restated in semantically
      related clinical terms in 246 (45.3%) instances. Nearly one third (31%) of
      subjective expressions were not coded or restated in standard terminology. The
      results highlight the diversity of symptom descriptions and the opportunities to
      further develop natural language processing to extract symptom expressions that
      are unobtainable by other automated methods. 

PMID- 24303239
TI  - App Store for EHRs and Patients Both.
AB  - The Substitutable Medical Applications, Reusable Technologies (SMART) Platforms
      project ( www.smartplatforms.org ) seeks to develop an iPhone-like health
      information technology platform with substitutable apps constructed around core
      services. It is funded by a grant from the Office of the National Coordinator of
      Health Information Technology's Strategic Health IT Advanced Research Projects
      (SHARP) Program. SMART technologies enable existing electronic health records and
      HIT platforms to run substitutable apps. Substitutability is the capability
      inherent in a system of replacing one application with another of similar
      functionality. We created a patient-facing SMART instance using the open source
      Indivo personally controlled health record (PCHR). The SMART "read-only" API has
      been deployed on multiple systems, including the Cerner installation at Boston
      Children's Hospital and the World Vista EHR. We sought to SMART-enable Indivo,
      the open source reference PCHR upon which HealthVault and other PCHRs were
      modeled. PCHRs provide patients with a secure repository of their health
      information that can be exposed to apps across a programming interface. We
      updated the open source Indivo PCHR to support the SMART API, enabling Indivo to
      act as a patient-facing apps platform, running the same or similar versions of
      apps that face clinicians. 

PMID- 24303240
TI  - How many patients are "normal"? Only 1.55%.
AB  - When conducting a clinical study, a "normal" control population is often desired.
      Identifying normal patients in a clinical data repository (CDR) can be
      challenging because healthy patients do not go the hospital; and, because
      patients receive care from multiple hospitals, the absence of a diagnosis in one
      hospital's electronic health record does not mean a patient does not have the
      disease. We define a set of 10 simple heuristic filters to eliminate patients who
      would seemingly be poor candidates for a normal control (e.g., chronic
      conditions, rare diseases, no recent data, etc.). Surprisingly, out of 2,019,774
      patients at two large academic hospitals, these filters excluded all but 31,352
      (1.55%). This illustrates how difficult it can be to identify control cohorts,
      and it raises questions of what it truly means to be normal. 

PMID- 24303241
TI  - A comprehensive framework for data quality assessment in CER.
AB  - The panel addresses the urgent need to ensure that comparative effectiveness
      research (CER) findings derived from diverse and distributed data sources are
      based on credible, high-quality data; and that the methods used to assess and
      report data quality are consistent, comprehensive, and available to data
      consumers. The panel consists of representatives from four teams leveraging
      electronic clinical data for CER, patient centered outcomes research (PCOR), and
      quality improvement (QI) and seeks to change the current paradigm where data
      quality assessment (DQA) is performed "behind the scenes" using one-off project
      specific methods. The panelists will present their process of harmonizing
      existing models for describing and measuring clinical data quality and will
      describe a comprehensive integrated framework for assessing and reporting DQA
      findings. The collaborative project is supported by the Electronic Data Methods
      (EDM) Forum, a three-year grant from the Agency for Healthcare Research and
      Quality (AHRQ) to facilitate learning and foster collaboration across a set of
      CER, PCOR, and QI projects designed to build infrastructure and methods for
      collecting and analyzing prospective data from electronic clinical data . 

PMID- 24303242
TI  - Characterization of the biomedical query mediation process.
AB  - To most medical researchers, databases are obscure black boxes. Query analysts
      are often indispensable guides aiding researchers to perform mediated data
      queries. However, this approach does not scale up and is time-consuming and
      expensive. We analyzed query mediation dialogues to inform future designs of
      intelligent query mediation systems. Thirty-one mediated query sessions for 22
      research projects were recorded and transcribed. We analyzed 10 of these to
      develop an annotation schema for dialogue acts through iterative refinement.
      Three coders independently annotated all 3160 dialogue acts. We assessed the
      inter-rater agreement and resolved disagreement by group consensus. This study
      contributes early knowledge of the query negotiation space for medical research.
      We conclude that research data query formulation is not a straightforward
      translation from researcher data needs to database queries, but rather iterative,
      process-oriented needs assessment and refinement. 

PMID- 24303243
TI  - Don't take your EHR to heaven, donate it to science: legal and research policies
      for EHR post mortem.
AB  - Electronic Health Records (EHR) represent a valuable research source. We explore
      legal and research policies governing EHR use after a patient's death. We
      describe how the EHR is used after patient's death and how deceased status
      impacts laws and regulations governing such record. We explore the patient
      consent mechanism that would support creation of a separate deceased subject
      integrated data repository (dsIDR) and discuss potential benefit of such
      repository in comparison with existing query tools, such as the i2b2 cohort
      estimation query tool, which operate under IRB exemption for reviews preparatory
      for research. Governance of dsIDR data is compared to regulatory frameworks
      governing post-mortem management of tissues, organs and corpses as well as
      digital afterlife of non-healthcare private data. 

PMID- 24303244
TI  - Learning signals of adverse drug-drug interactions from the unstructured text of
      electronic health records.
AB  - Drug-drug interactions (DDI) account for 30% of all adverse drug reactions, which
      are the fourth leading cause of death in the US. Current methods for post
      marketing surveillance primarily use spontaneous reporting systems for learning
      DDI signals and validate their signals using the structured portions of
      Electronic Health Records (EHRs). We demonstrate a fast, annotation-based
      approach, which uses standard odds ratios for identifying signals of DDIs from
      the textual portion of EHRs directly and which, to our knowledge, is the first
      effort of its kind. We developed a gold standard of 1,120 DDIs spanning 14
      adverse events and 1,164 drugs. Our evaluations on this gold standard using
      millions of clinical notes from the Stanford Hospital confirm that identifying
      DDI signals from clinical text is feasible (AUROC=81.5%). We conclude that the
      text in EHRs contain valuable information for learning DDI signals and has
      enormous utility in drug surveillance and clinical decision support. 

PMID- 24303245
TI  - ADEpedia 2.0: Integration of Normalized Adverse Drug Events (ADEs) Knowledge from
      the UMLS.
AB  - A standardized Adverse Drug Events (ADEs) knowledge base that encodes known ADE
      knowledge can be very useful in improving ADE detection for drug safety
      surveillance. In our previous study, we developed the ADEpedia that is a
      standardized knowledge base of ADEs based on drug product labels. The objectives
      of the present study are 1) to integrate normalized ADE knowledge from the
      Unified Medical Language System (UMLS) into the ADEpedia; and 2) to enrich the
      knowledge base with the drug-disorder co-occurrence data from a 51-million
      document electronic medical records (EMRs) system. We extracted 266,832 drug
      disorder concept pairs from the UMLS, covering 14,256 (1.69%) distinct drug
      concepts and 19,006 (3.53%) distinct disorder concepts. Of them, 71,626 (26.8%)
      concept pairs from UMLS co-occurred in the EMRs. We performed a preliminary
      evaluation on the utility of the UMLS ADE data. In conclusion, we have built an
      ADEpedia 2.0 framework that intends to integrate known ADE knowledge from
      disparate sources. The UMLS is a useful source for providing standardized ADE
      knowledge relevant to indications, contraindications and adverse effects, and
      complementary to the ADE data from drug product labels. The statistics from EMRs
      would enable the meaningful use of ADE data for drug safety surveillance. 

PMID- 24303246
TI  - Pains and palliation in distributed research networks: lessons from the field.
AB  - Large-scale comparative effectiveness research studies require detailed clinical
      data collected across disparate clinical practice settings and institutions.
      Distributed research networks (DRNs) have been promoted as one approach to wide
      scale data sharing that enables data sharing organizations to retain local data
      ownership and access control. Despite significant investments in distributed data
      sharing technologies, clinical research networks using distributed methods remain
      difficult to implement due to a broad range of organizational and technical
      barriers. The panelists represent four different research networks are in
      different stages of implementation maturity and are leveraging different
      informatics technologies. Challenges common to all DRNs include governance,
      semantic interoperability, and identity management. This panel will describe some
      of the critical challenges and experimental solutions to implementing, expanding,
      and sustaining DRNs. Each panelist will focus on a specific challenge that
      requires new informatics tools to reduce barriers to participation and data
      sharing. 

PMID- 24303247
TI  - Automatic Extraction of ICD-O-3 Primary Sites from Cancer Pathology Reports.
AB  - Although registry specific requirements exist, cancer registries primarily
      identify reportable cases using a combination of particular ICD-O-3 topography
      and morphology codes assigned to cancer case abstracts of which free text
      pathology reports form a main component. The codes are generally extracted from
      pathology reports by trained human coders, sometimes with the help of software
      programs. Here we present results that improve on the state-of-the-art in
      automatic extraction of 57 generic sites from pathology reports using three
      representative machine learning algorithms in text classification. We use a
      dataset of 56,426 reports arising from 35 labs that report to the Kentucky Cancer
      Registry. Employing unigrams, bigrams, and named entities as features, our
      methods achieve a class-based micro F-score of 0.9 and macro F-score of 0.72. To
      our knowledge, this is the best result on extracting ICD-O-3 codes from pathology
      reports using a large number of possible codes. Given the large dataset we use
      (compared to other similar efforts) with reports from 35 different labs, we also
      expect our final models to generalize better when extracting primary sites from
      previously unseen reports. 

PMID- 24303248
TI  - EHR-based Clinical Trial Alert Effects on Recruitment to a Neurology Trial across
      Institutions: Interim Analysis of a Randomized Controlled Study.
AB  - EHR-based, point-of-care, clinical trial alerts (CTAs) have shown promise in
      prior studies to improve subject recruitment rates, but those studies have had
      limitations of generalizability. We report here an interim analysis of a cluster
      randomized controlled trial of the CTA approach applied to a neurology study at a
      second institution to test the efficacy of the approach across institutions with
      a different EHR. During the first phase (4 months) of our study, the CTA
      significantly improved physician-generated referrals among intervention
      physicians vs. control physicians (35 vs. 0). Additional trends and information
      about the usage of CTA features have also been gleaned. These findings add to the
      limited evidence for the utility and generalizability of the CTA approach. 

PMID- 24303249
TI  - Mining Genotype-Phenotype Associations from Public Knowledge Sources via Semantic
      Web Querying.
AB  - Gene Wiki Plus (GeneWiki+) and the Online Mendelian Inheritance in Man (OMIM) are
      publicly available resources for sharing information about disease-gene and gene
      SNP associations in humans. While immensely useful to the scientific community,
      both resources are manually curated, thereby making the data entry and
      publication process time-consuming, and to some degree, error-prone. To this end,
      this study investigates Semantic Web technologies to validate existing and
      potentially discover new genotype-phenotype associations in GWP and OMIM. In
      particular, we demonstrate the applicability of SPARQL queries for identifying
      associations not explicitly stated for commonly occurring chronic diseases in GWP
      and OMIM, and report our preliminary findings for coverage, completeness, and
      validity of the associations. Our results highlight the benefits of Semantic Web
      querying technology to validate existing disease-gene associations as well as
      identify novel associations although further evaluation and analysis is required
      before such information can be applied and used effectively. 

PMID- 24303250
TI  - Supporting the Health Quality Measures Format in i2b2.
AB  - The Health Quality Measures Format (HQMF) is an HL7 standard for expressing
      computable queries of clinical data. It is becoming increasingly consequential
      for both quality measurement and population health research. A variety of
      national leadership is involved in its development and deployment, including the
      Meaningful Use incentive program, the Query Health initiative, the Joint
      Commission, the National Quality Forum (NQF), and the Food and Drug
      Administration. Here we analyze the structure of HQMF and apply this to
      computation of HQMF on Informatics for Integrating Biology and the Bedside
      (i2b2). i2b2 is a widely used, modular, open-source clinical research data
      repository. We implement a translator to convert between HQMF and i2b2-XML format
      that covers the subset of HQMF supported in i2b2-XML, which will be expanded in
      the next release of i2b2. This translator is part of the freely-available
      reference implementation of the QueryHealth initiative. 

PMID- 24303251
TI  - Privacy-by-Design: Understanding Data Access Models for Secondary Data.
AB  - Today there is a constant flow of data into, out of, and between ever-larger and
      ever-more complex databases about people. Together, these digital traces
      collectively capture our social genome , the footprints of our society. The
      burgeoning field of population informatics is the systematic study of populations
      via secondary analysis of such massive data collections (termed "big data") about
      people. In particular, health informatics analyzes electronic health records to
      improve health outcomes for a population. Privacy protection in such secondary
      data analysis research is complex and requires a holistic approach which combines
      technology, statistics, policy and a shift in culture of information
      accountability through transparency rather than secrecy. We review state of the
      art in privacy protection technology and policy frameworks from widely different
      fields, and synthesize the findings to present a comprehensive system of privacy
      protection in population informatics research using the privacy-by-design
      approach. Based on common activities in the workflow, we describe the pros and
      cons of four different data access models - restricted access, controlled access,
      monitored access, and open access - that minimize risk and maximize usability of
      data. We then evaluate the system by analyzing the risk and usability of data
      through a realistic example. We conclude that deployed together the four data
      access models can provide a comprehensive system for privacy protection,
      balancing the risk and usability of secondary data in population informatics
      research. 

PMID- 24303252
TI  - Biobanking informatics infrastructure to support clinical and translational
      research.
AB  - The University of Utah Health Sciences (UUHSC) and Intermountain Healthcare (IH)
      support high value clinical and translational research programs. The Utah
      Biohealth Initiative will facilitate next generation research by leveraging the
      combined resources of both institutions through an infrastructure which links
      biospecimens and electronic health records (EHR). During phase I of the Utah
      BioHealth Initiative (UBI) the participating institutions developed a legal,
      regulatory and information technology infrastructure that supports clinical and
      translational research, and advances our understanding of health and disease,
      improves healthcare value and health for current and future generations of
      Utahns. We used the Federated Utah Research and Translational Health electronic
      Repository (FURTHeR) 1 to combine EHR and biospecimen data from an actual study
      populated by both institutions to demonstrate the robustness of the
      infrastructure. 

PMID- 24303253
TI  - 3D Sensing Algorithms Towards Building an Intelligent Intensive Care Unit.
AB  - Intensive Care Units (ICUs) are chaotic places where hundreds of tasks are
      carried out by many different people. Timely and coordinated execution of these
      tasks are directly related to quality of patient outcomes. An improved
      understanding of the current care process can aid in improving quality. Our goal
      is to build towards a system that automatically catalogs various tasks being
      performed by the bedside. We propose a set of techniques using computer vision
      and machine learning to develop a system that passively senses the environment
      and identifies seven common actions such as documenting, checking up on a
      patient, and performing a procedure. Preliminary evaluation of our system on 5.5
      hours of data from the Pediatric ICU obtains overall task recognition accuracy of
      70%. Furthermore, we show how it can be used to summarize and visualize tasks.
      Our system provides a significant departure from current approaches used for
      quality improvement. With further improvement, we think that such a system could
      realistically be deployed in the ICU. 

PMID- 24303254
TI  - Using association rule mining for phenotype extraction from electronic health
      records.
AB  - The increasing adoption of electronic health records (EHRs) due to Meaningful Use
      is providing unprecedented opportunities to enable secondary use of EHR data.
      Significant emphasis is being given to the development of algorithms and methods
      for phenotype extraction from EHRs to facilitate population-based studies for
      clinical and translational research. While preliminary work has shown
      demonstrable progress, it is becoming increasingly clear that developing,
      implementing and testing phenotyping algorithms is a time- and resource-intensive
      process. To this end, in this manuscript we propose an efficient machine learning
      technique-distributional associational rule mining (ARM)-for semi-automatic
      modeling of phenotyping algorithms. ARM provides a highly efficient and robust
      framework for discovering the most predictive set of phenotype definition
      criteria and rules from large datasets, and compared to other machine learning
      techniques, such as logistic regression and support vector machines, our
      preliminary results indicate not only significantly improved performance, but
      also generation of rule patterns that are amenable to human interpretation . 

PMID- 24303255
TI  - An information extraction framework for cohort identification using electronic
      health records.
AB  - Information extraction (IE), a natural language processing (NLP) task that
      automatically extracts structured or semi-structured information from free text,
      has become popular in the clinical domain for supporting automated systems at
      point-of-care and enabling secondary use of electronic health records (EHRs) for
      clinical and translational research. However, a high performance IE system can be
      very challenging to construct due to the complexity and dynamic nature of human
      language. In this paper, we report an IE framework for cohort identification
      using EHRs that is a knowledge-driven framework developed under the Unstructured
      Information Management Architecture (UIMA). A system to extract specific
      information can be developed by subject matter experts through expert knowledge
      engineering of the externalized knowledge resources used in the framework. 

PMID- 24303256
TI  - Dissecting the Ambiguity of FMA Concept Names Using Taxonomy and Partonomy
      Structural Information.
AB  - The complex inner structures of concept names in the Foundational Model of
      Anatomy (FMA) remain an obstacle for further analyzing the ontology using lexical
      methods. A very common problem is the ambiguity lying in names with the sometimes
      multiple occurrences of the preposition "of." In this paper, we propose an
      automatic method to help disambiguating FMA terms by leveraging the taxonomy and
      partonomy information. If a sub-phrase of a concept name also appears in its
      parents, it is likely to occur as a sub-tree in its parse tree, hence should be
      parsed as such. We classified all the concept names with a single occurrence of
      the preposition "of" by the appearances of their sub-phrases in the parent names
      using three test suites. Results show that more than 90% of them can be provided
      with useful information to assist their correct parsing. 

PMID- 24303257
TI  - Next-generation registries: fusion of data for care, and research.
AB  - Disease-based registries are a critical tool for electronic data capture of high
      quality, gold standard data for clinical research as well as for population
      management in clinical care. Yet, a legacy of significant operational costs,
      resource requirements, and poor data liquidity have limited their use. Research
      registries have engendered more than $3 Billion in HHS investment over the past
      17 years. Health delivery systems and Accountable Care Organizations are
      investing heavily in registries to track care quality and follow-up of patient
      panels. Despite the investment, regulatory and financial models have often
      enforced a "single purpose" limitation on each registry, restricting the use of
      data to a pre-defined set of protocols. The need for cost effective, multi
      sourced, and widely shareable registry data sets has never been greater, and
      requires next-generation platforms to robustly support multi-center studies,
      comparative effectiveness research, post-marketing surveillance and disease
      management. This panel explores diverse registry efforts, both academic and
      commercial, that have been implemented in leading-edge clinical, research, and
      hybrid use cases. Panelists present their experience in these areas as well as
      lessons learned, challenges addressed, and near innovations and advances. 

PMID- 24303258
TI  - Visualizing the data - using lifelines2 to gain insights from data drawn from a
      clinical data repository.
AB  - The field of visual analytics continues to expand into the realm of electronic
      health record (EHR) analysis. At the National Institutes of Health (NIH),
      Lifelines2, a visualization program from the University of Maryland's Human
      Computer Interaction Laboratory, was recently integrated into the NIH's clinical
      repository, the Biomedical Translational Research Information System (BTRIS). To
      explore the functionality of Lifelines2, two markers of inflammation -
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - were compared
      on patients both with and without the rare immune disorder chronic granulomatous
      disease (CGD) using ten years of de-identified patient data. We used Lifelines2
      to visualize correlations among 12,266 laboratory events on 622 patients. The
      findings from our unrestricted sample identify areas warranting further studies
      on population subsets in which clinical features (such as disease activity) are
      known. Overall, visual aids such as Lifelines2 allowed for both rapid and
      powerful interpretation of EHR data. 

PMID- 24303259
TI  - Open Research Networking Gadgets (ORNG).
AB  - In 2009, UCSF embarked on a journey to utilize industry-backed application
      standards to extend our research networking tool of choice, Profiles, into a
      software platform. The goal of this work was to bring extended data and
      functionality to our researchers' online environment and make it easier to share
      independently-developed software innovations with others. We used the OpenSocial
      standard to achieve these ends. In 2012 we extended the OpenSocial standard to
      support RDF and the VIVO Ontology in an effort titled "Open Research Network
      Gadgets" or ORNG. Our work has been adopted by two major academic open source
      research networking tools - Harvard Catalyst Profiles and VIVO, and the ORNG
      standard is now available for use by the 50+ institutions that use recent
      versions of the two software products. 

PMID- 24303260
TI  - How much does automatic text de-identification impact clinical problems, tests,
      and treatments?
AB  - Clinical text de-identification can potentially overlap with clinical information
      such as medical problems or treatments, therefore causing this information to be
      lost. In this study, we focused on the analysis of the overlap between the 2010
      i2b2 NLP challenge concept annotations, with the PHI annotations of our best-of
      breed clinical text de-identification application. Overall, 0.81% of the
      annotations overlapped exactly, and 1.78% partly overlapped. 

PMID- 24303261
TI  - Towards dynamic and interactive retrieval of clinical trials using common
      eligibility features.
AB  - Information overload remains a significant barrier for patients searching for
      clinical trials online. We present a framework to dynamically refine clinical
      trial search results towards a manually reviewable number of studies. At this
      aim, a set of frequent features are extracted automatically offline from the
      eligibility criteria of a representative subset of clinical trials. These
      features are then presented dynamically to the users based on feature co
      occurrences and user interactions to reduce the number of resulting documents.
      Experiments on ClinicalTrials.gov showed that using an average of four features,
      it is feasible to reduce the results of a simple search from over a thousand to
      ten. 

PMID- 24303262
TI  - Diagnostic Prediction of Von Willebrand Disease using Multiple Bleeding Phenomics
      Datasets.
AB  - The rigorous assessment of bleeding symptoms is a key component in establishing a
      diagnosis in patients suspected of having von Willebrand disease (VWD) and other
      inherited bleeding disorders. Multiple bleeding questionnaires have been
      developed and validated to capture bleeding history phenotypes for assessing
      patients with bleeding disorders. In this study we developed a prediction model
      based on Naive Bayes decision tree classifier by analyzing various phenotypic
      attributes derived from multiple bleeding questionnaires. We evaluated the
      classification effectiveness derived from the top 25 attributes with highest
      discriminations on prediction of VWD. We used data from 952 patients and the
      classifier achieved a precision of 95%, recall of 94%, and a Receiving Operating
      Curve (ROC) area under the curve of 0.97. 

PMID- 24303263
TI  - Development of an electronic research permissions management system to enhance
      informed consents and capture research authorizations data.
AB  - Informed consents are a critical and essential component of the clinical research
      process. Currently, most consents and research privacy authorizations are being
      captured on paper. In this paper we describe a novel method of capturing this
      information electronically. The objective is to allow easier tracking of research
      participants' intent for current and future research involvement, enhance consent
      comprehension and facilitate the research workflow. After multidisciplinary
      analysis in key hospital registration areas and research participant enrollment,
      an open source software product was designed to capture this data through a user
      friendly touch screen interface. The data may then be fed into a clinical data
      warehouse for use in cohort discovery or consent tracking. Despite ethical, legal
      and informatics challenges in clinical and research environments, we propose that
      this technology opens new avenues for significantly enhancing the consent process
      and positively impacting recruitment. 

PMID- 24303264
TI  - An iOS Framework for the Indivo X Personally Controlled Health Record.
AB  - The Indivo X personally controlled health record creates a channel between
      researchers and the patient/subject in several large scale projects. Indivo
      enables patients to access their health data through a web interface and, as an
      "apps platform", can be extended in functionality. Patient-facing apps, such as a
      medication list, may improve the data flow between researcher and patient, in
      both directions, and as such provide better data for the researcher and immediate
      benefit for the patient. However, research projects in general do not allocate
      large funds to patient facing apps, let alone a mobile interface. Thus we have
      created a framework that greatly simplifies connecting an iOS app to an Indivo X
      server. Our open-source framework enables novel as well as experienced iOS
      developers to build mobile interfaces for their research subjects, taking
      advantage of Indivo X. 

PMID- 24303265
TI  - Semantic ETL into i2b2 with Eureka!
AB  - Clinical phenotyping is an emerging research information systems capability.
      Research uses of electronic health record (EHR) data may require the ability to
      identify clinical co-morbidities and complications. Such phenotypes may not be
      represented directly as discrete data elements, but rather as frequency,
      sequential and temporal patterns in billing and clinical data. These patterns'
      complexity suggests the need for a robust yet flexible extract, transform and
      load (ETL) process that can compute them. This capability should be accessible to
      investigators with limited ability to engage an IT department in data management.
      We have developed such a system, Eureka! Clinical Analytics. It extracts data
      from an Excel spreadsheet, computes a broad set of phenotypes of common interest,
      and loads both raw and computed data into an i2b2 project. A web-based user
      interface allows executing and monitoring ETL processes. Eureka! is deployed at
      our institution and is available for deployment in the cloud. 

PMID- 24303266
TI  - Creating a Research and Clinical Care Partnership through EMR and Clinical
      Research System Integration.
AB  - EMRs are essential in modern healthcare. At the same time there has been the
      rapid development of clinical research systems (CRS) which offer specific tools
      to facilitate research protocol development, execution and management. However,
      examples of integrating a commercial EMR and CRS are rare. We describe our
      experience in the analysis, resolution of issues, design, and implementation of
      EMR/CR integration in a large academic medical center with affiliated hospitals.
      Our initial results suggest that (1) neither the EMR nor CRS system alone will
      suffice to facilitate clinical research, (2) there are important benefits to
      integration of the EMR and CRS systems and (3) this integration can be leveraged
      across multiple institutions. 

PMID- 24303267
TI  - Bias in recording of body mass index data in the electronic health record.
AB  - The relationship between patient disease status and the presence or absence of
      body mass index (BMI) data in the electronic health record (EHR) has not been
      characterized. We conducted a descriptive study of the completeness of BMI data
      for three patient cohorts. Cross-sectional descriptions of BMI presence rates per
      patient were compared between a cohort having at least one ICD-9-CM code for
      diabetes mellitus (DM) versus a cohort with no diagnosis constraints. Conversely,
      frequencies of encounter diagnoses were compared among subgroups having BMI
      recorded or not in both cohorts described and a third cohort having DM codes from
      a separate organization's EHR. The data demonstrate a correlation with presence
      of BMI and higher disease status. This effect may bias the cohort average BMIs,
      which appear higher than expected. When EHR BMI data are repurposed for research,
      biases in the selective recording of BMI may affect the results. 

PMID- 24303268
TI  - Extracting actionable findings of appendicitis from radiology reports using
      natural language processing.
AB  - Radiology reports often contain findings about the condition of a patient which
      should be acted upon quickly. These actionable findings in a radiology report can
      be automatically detected to ensure that the referring physician is notified
      about such findings and to provide feedback to the radiologist that further
      action has been taken. In this paper we investigate a method for detecting
      actionable findings of appendicitis in radiology reports. The method identifies
      both individual assertions regarding the presence of appendicitis and other
      findings related to appendicitis using syntactic dependency patterns. All
      relevant individual statements from a report are collectively considered to
      determine whether the report is consistent with appendicitis. Evaluation on a
      corpus of 400 radiology reports annotated by two expert radiologists showed that
      our approach achieves a precision of 91%, a recall of 83%, and an F1-measure of
      87%. 

PMID- 24303269
TI  - Augmenting EHR-Derived Clinical Data with Geographic-Level Public Information to
      Develop Research Hypotheses for Population Obesity Rates.
AB  - Obesity adversely affects not just individuals but populations, and it is a major
      problem for our society. Environmental and socioeconomic factors influence
      obesity and are potentially important for research, yet these data are often not
      readily available in electronic health records (EHRs). We augmented an EHR
      derived clinical data set with publicly available data on factors thought to
      influence obesity rates to examine associations between these factors and the
      prevalence of overweight and obesity. As revealed by our multinomial logistic
      model for overweight and obesity in a diverse region, this study demonstrates the
      potential value for augmenting the secondary use of EHR data with publicly
      available data. 

PMID- 24303270
TI  - DEDUCE Clinical Text: An Ontology-based Module to Support Self-Service Clinical
      Notes Exploration and Cohort Development.
AB  - Large amounts of information, as well as opportunities for informing research,
      education, and operations, are contained within clinical text such as radiology
      reports and pathology reports. However, this content is less accessible and
      harder to leverage than structured, discrete data. We report on an extension to
      the Duke Enterprise Data Unified Content Explorer (DEDUCE), a self-service query
      tool developed to provide clinicians and researchers with access to data within
      the Duke Medicine Enterprise Data Warehouse (EDW). The DEDUCE Clinical Text
      module supports ontology-based text searching, enhanced filtering capabilities
      based on document attributes, and integration of clinical text with structured
      data and cohort development. The module is implemented with open-source tools
      extensible to other institutions, including a Java-based search engine (Apache
      Solr) with complementary full-text indexing library (Lucene) employed with a
      negation engine (NegEx) modified by clinical users to include to local domain
      specific negation phrases. 

PMID- 24303271
TI  - Framework for Curating and Applying Data Elements within Continuing Use Data: A
      Case Study from the Durham Diabetes Coalition.
AB  - Data within a continuing use context (also known as secondary use) can require
      translation into the variables necessary for project analysis. We have developed
      and applied a framework in which: Project objectives inform the curation of data
      elements. Data elements are rendered into system-readable metadata. Metadata are
      applied to the source data and used to produce data sets. This process
      distinguishes between data sets and source data. Data sets contain project
      specific variables that are structured for analytic activities. This can differ
      from source data, which may be stored in a structure dictated by the original
      source system for data collection, or in a data structure contrary to what is
      desired for analysis. Data elements mediate this translation, and the process of
      curation refines their definitions and associated attributes. This framework
      improves analysis workflow through the application of best practices, consistent
      processes, and centralized decision-making. 

PMID- 24303272
TI  - SPARC: A Multi-institutional Integrated Web Based Research Management System.
AB  - SPARC is a web-based research management system that integrates both research and
      routine clinical care work flows and has now been in operation at the Medical
      University of South Carolina (MUSC) since March 1, 2012. The system provides a
      one-stop-shop to researchers for all service requests related to their research
      with a focus on billing compliance, proposal and budget development, and work
      fulfillment data collection. Upgrades and enhancements based on user feedback
      from institutions around the country include increased invoicing and billing
      functionality, clinical research visit and assessment tracking, and outcome
      assessment using grant and publication data links. System development leverages
      home grown and community open source components. 

PMID- 24303273
TI  - An ontology-based method for secondary use of electronic dental record data.
AB  - A key question for healthcare is how to operationalize the vision of the Learning
      Healthcare System, in which electronic health record data become a continuous
      information source for quality assurance and research. This project presents an
      initial, ontology-based, method for secondary use of electronic dental record
      (EDR) data. We defined a set of dental clinical research questions; constructed
      the Oral Health and Disease Ontology (OHD); analyzed data from a commercial EDR
      database; and created a knowledge base, with the OHD used to represent clinical
      data about 4,500 patients from a single dental practice. Currently, the OHD
      includes 213 classes and reuses 1,658 classes from other ontologies. We have
      developed an initial set of SPARQL queries to allow extraction of data about
      patients, teeth, surfaces, restorations and findings. Further work will establish
      a complete, open and reproducible workflow for extracting and aggregating data
      from a variety of EDRs for research and quality assurance. 

PMID- 24303274
TI  - Clinical and research data integration: the i2b2-FSM experience.
AB  - In order to support and improve the efficiency of clinical research in specific
      health area, the University of Pavia and the IRCCS Fondazione Salvatore Maugeri
      of Pavia (FSM) are developing and implementing an i2b2 based platform, designed
      to collect data coming from hospital clinical practice and scientific research.
      The work made in FSM is committed to support an affordable, less intrusive and
      more personalized care, increasing the quality of clinical practice as well as
      improving the scientific results. Such a aim depends on the application of
      information and communication technologies and the use of data. An integrated
      data warehouse has been implemented to support clinicians and researchers in two
      medical fields with a great impact on the population: oncology and cardiology.
      Furthermore the data warehouse approach has been tested with administrative
      information, allowing a financial view of clinical data. 

PMID- 24303275
TI  - Radiology diagnostic exchange agents: clinical term identification and
      validation.
AB  - Diagnostic radiology is one of the key areas of clinical diagnosis on which much
      of the health care system is built. Along with pathology, radiology has a unique
      role in providing diagnostic information for prognosis, treatment, and management
      of clinical conditions. This role is clinically challenging due to the problems
      of knowledge management associated with the free-text radiology reports which are
      currently the standard of practice for radiology care. In order to address this
      critical knowledge management problem, we have proposed a solution using the
      Radiology Diagnostics Exchange Agent, which is under development and will enhance
      clinical care management. Using a human computation approach, we have started to
      identify and validate clinically actionable terms on which an information
      management infrastructure can be developed with important implications for
      clinical care and research. 

PMID- 24303277
TI  - PROCenf evaluation: Are the assessments triggering the correct NANDA-I diagnoses?
AB  - PROCEnf-USP is a decision support system that offers staff nurses at the
      University Hospital in Sao Paulo, Brazil a set of questionnaires to guide patient
      assessment. Using the answers, the system computes probabilities for nursing
      diagnoses based on NANDA-I. This study aims to evaluate PROCenf in terms of its
      reliability (Does it consistently gives the right diagnose?) and its validity in
      Brazil (Does NANDA-I terminology represent the healthcare experience of a
      Brazilian population). 

PMID- 24303276
TI  - Identifying Abdominal Aortic Aneurysm Cases and Controls using Natural Language
      Processing of Radiology Reports.
AB  - Prevalence of abdominal aortic aneurysm (AAA) is increasing due to longer life
      expectancy and implementation of screening programs. Patient-specific
      longitudinal measurements of AAA are important to understand pathophysiology of
      disease development and modifiers of abdominal aortic size. In this paper, we
      applied natural language processing (NLP) techniques to process radiology reports
      and developed a rule-based algorithm to identify AAA patients and also extract
      the corresponding aneurysm size with the examination date. AAA patient cohorts
      were determined by a hierarchical approach that: 1) selected potential AAA
      reports using keywords; 2) classified reports into AAA-case vs. non-case using
      rules; and 3) determined the AAA patient cohort based on a report-level
      classification. Our system was built in an Unstructured Information Management
      Architecture framework that allows efficient use of existing NLP components. Our
      system produced an F-score of 0.961 for AAA-case report classification with an
      accuracy of 0.984 for aneurysm size extraction. 

PMID- 24303278
TI  - Biomedical Terminology Mapper for UML projects.
AB  - As the biomedical community collects and generates more and more data, the need
      to describe these datasets for exchange and interoperability becomes crucial.
      This paper presents a mapping algorithm that can help developers expose local
      implementations described with UML through standard terminologies. The input UML
      class or attribute name is first normalized and tokenized, then lookups in a UMLS
      based dictionary are performed. For the evaluation of the algorithm 142 UML
      projects were extracted from caGrid and automatically mapped to National Cancer
      Institute (NCI) terminology concepts. Resulting mappings at the UML class and
      attribute levels were compared to the manually curated annotations provided in
      caGrid. Results are promising and show that this type of algorithm could speed-up
      the tedious process of mapping local implementations to standard biomedical
      terminologies. 

PMID- 24303279
TI  - Identifying inference attacks against healthcare data repositories.
AB  - Health care data repositories play an important role in driving progress in
      medical research. Finding new pathways to discovery requires having adequate data
      and relevant analysis. However, it is critical to ensure the privacy and security
      of the stored data. In this paper, we identify a dangerous inference attack
      against naive suppression based approaches that are used to protect sensitive
      information. We base our attack on the querying system provided by the Healthcare
      Cost and Utilization Project, though it applies in general to any medical
      database providing a query capability. We also discuss potential solutions to
      this problem. 

PMID- 24303280
TI  - Workflow-based Data Reconciliation for Clinical Decision Support: Case of
      Colorectal Cancer Screening and Surveillance.
AB  - A major barrier for computer-based clinical decision support (CDS), is the
      difficulty in obtaining the patient information required for decision making. The
      information gap is often due to deficiencies in the clinical documentation. One
      approach to address this gap is to gather and reconcile data from related
      documents or data sources. In this paper we consider the case of a CDS system for
      colorectal cancer screening and surveillance. We describe the use of workflow
      analysis to design data reconciliation processes. Further, we perform a
      quantitative analysis of the impact of these processes on system performance
      using a dataset of 106 patients. Results show that data reconciliation
      considerably improves the performance of the system. Our study demonstrates that,
      workflow-based data reconciliation can play a vital role in designing new
      generation CDS systems that are based on complex guideline models and use natural
      language processing (NLP) to obtain patient data. 

PMID- 24303281
TI  - Automated tools for phenotype extraction from medical records.
AB  - Clinical research studying critical illness phenotypes relies on the
      identification of clinical syndromes defined by consensus definitions.
      Historically, identifying phenotypes has required manual chart review, a time and
      resource intensive process. The overall research goal of C ritical I llness PH
      enotype E xt R action (deCIPHER) project is to develop automated approaches based
      on natural language processing and machine learning that accurately identify
      phenotypes from EMR. We chose pneumonia as our first critical illness phenotype
      and conducted preliminary experiments to explore the problem space. In this
      abstract, we outline the tools we built for processing clinical records, present
      our preliminary findings for pneumonia extraction, and describe future steps. 

PMID- 24303282
TI  - Merging Ontology Navigation with Query Construction for Web-based Medicare Data
      Exploration.
AB  - To enhance web-based exploration of Medicare data, we present a unique query
      interface merging ontology navigation with query construction, for cohort
      discovery based on demographics, disease classification codes, medication and
      other types of clinical data. Our interface seamlessly blends query construction
      with functions for hierarchical browsing and rendering of terms and associated
      codes from vocabulary systems and ontologies, such as International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). By
      unifying ontology navigation activities with query widget generation, a user can
      perform fine-tuned full boolean queries based on the substructure of the
      ontology, with flexibility to enable or disable subsumption-based queries. Query
      performance were evaluated on top disease subtypes of Centers for Medicare and
      Medicaid Services data, consisting of 5% of 2009 Limited Data Set files
      (inpatient and outpatient). Such interfaces will help moving the data access
      paradigm from a hypothesis-driven style to a data-driven one, while improving
      efficiency as a collective "secondary-use user community." 

PMID- 24303283
TI  - Using clinical element models for pharmacogenomic study data standardization.
AB  - Standardized representations for pharmacogenomics data are seldom used, which
      leads to data heterogeneity and hinders data reuse and integration. In this
      study, we attempted to represent data elements from the Pharmacogenomics Research
      Network (PGRN) that are related to four categories, patient, drug, disease and
      laboratory, in a standard way using Clinical Element Models (CEMs), which have
      been adopted in the Strategic Health IT Advanced Research Project, secondary use
      of EHR (SHARPn) as a library of common logical models that facilitate consistent
      data representation, interpretation, and exchange within and across heterogeneous
      sources and applications. This was accomplished by grouping PGRN data elements
      into categories based on UMLS semantic type, then mapping each to one or more CEM
      attributes using a web-based tool that was developed to support curation
      activities. This study demonstrates the successful application of SHARPn CEMs to
      the pharmacogenomic domain. It also identified several categories of data
      elements that are not currently supported by SHARPn CEMs, which represent
      opportunities for further development and collaboration. 

PMID- 24303284
TI  - Automatic Classification of Free-Text Radiology Reports to Identify Limb
      Fractures using Machine Learning and the SNOMED CT Ontology.
AB  - OBJECTIVE: To develop and evaluate machine learning techniques that identify limb
      fractures and other abnormalities (e.g. dislocations) from radiology reports.
      MATERIALS AND METHODS: 99 free-text reports of limb radiology examinations were
      acquired from an Australian public hospital. Two clinicians were employed to
      identify fractures and abnormalities from the reports; a third senior clinician
      resolved disagreements. These assessors found that, of the 99 reports, 48
      referred to fractures or abnormalities of limb structures. Automated methods were
      then used to extract features from these reports that could be useful for their
      automatic classification. The Naive Bayes classification algorithm and two
      implementations of the support vector machine algorithm were formally evaluated
      using cross-fold validation over the 99 reports. RESULTS: Results show that the
      Naive Bayes classifier accurately identifies fractures and other abnormalities
      from the radiology reports. These results were achieved when extracting stemmed
      token bigram and negation features, as well as using these features in
      combination with SNOMED CT concepts related to abnormalities and disorders. The
      latter feature has not been used in previous works that attempted classifying
      free-text radiology reports. DISCUSSION: Automated classification methods have
      proven effective at identifying fractures and other abnormalities from radiology
      reports (F-Measure up to 92.31%). Key to the success of these techniques are
      features such as stemmed token bigrams, negations, and SNOMED CT concepts
      associated with morphologic abnormalities and disorders. CONCLUSION: This
      investigation shows early promising results and future work will further validate
      and strengthen the proposed approaches.

PMID- 24303285
TI  - Biotrust: a comprehensive system for acquiring and distributing biospecimens.
AB  - The Biotrust resource provides a web-accessible method to coordinate discovery
      and request of annotated biospecimens for research. The system is built on an
      open-source web-application framework, and has a modular approach to defining
      education on process, study registration and feasibility review, patient
      identification and cohort forwarding, consent tracking, and biospecimen
      processing/distribution. The architecture has been designed as a "pass through"
      system that provides annotated deidentified biospecimens for investigator use in
      a restricted time window of 4-7 days, and does not maintain biobanking
      facilities. As a core institutional resource, the system integrates seven
      vertical service arms, each of which can be accessed independently to support
      flexible and independent use in translational research. The system will be
      described in terms of requirements for use, metrics of evaluation, and lessons
      learned in integrating this into clinical and operational environments. 

PMID- 24303286
TI  - tranSMART: An Open Source and Community-Driven Informatics and Data Sharing
      Platform for Clinical and Translational Research.
AB  - tranSMART is an emerging global open source public private partnership community
      developing a comprehensive informatics-based analysis and data-sharing cloud
      platform for clinical and translational research. The tranSMART consortium
      includes pharmaceutical and other companies, not-for-profits, academic entities,
      patient advocacy groups, and government stakeholders. The tranSMART value
      proposition relies on the concept that the global community of users, developers,
      and stakeholders are the best source of innovation for applications and for
      useful data. Continued development and use of the tranSMART platform will create
      a means to enable "pre-competitive" data sharing broadly, saving money and,
      potentially accelerating research translation to cures. Significant
      transformative effects of tranSMART includes 1) allowing for all its user
      community to benefit from experts globally, 2) capturing the best of innovation
      in analytic tools, 3) a growing 'big data' resource, 4) convergent standards, and
      5) new informatics-enabled translational science in the pharma, academic, and not
      for-profit sectors. 

PMID- 24303287
TI  - How Cytokines Co-occur across Rickettsioses Patients: From Bipartite Visual
      Analytics to Mechanistic Inferences of a Cytokine Storm.
AB  - Several intersecting host, vector, and environmental factors have led to a re
      emergence of rickettsial diseases such as Mediterranean Spotted Fever (MSF), and
      Dermacentor spp.-borne necrosis-erythema lymphadenopathy (DEBONEL). Some
      rickettsiae produce diffuse endothelial infection and systemic microvascular
      leakage leading in some cases to high morbidity and mortality. Unfortunately,
      little is known about the molecular pathways triggered by these diseases in
      humans. We therefore analyzed how candidate cytokines co-occur across acutely-ill
      patients with either a localized (DEBONEL), or a systemic (MSF) form of
      rickettsiosis, using bipartite visual analytics. The results revealed a network
      core consisting of a small set of MSF patients exhibiting high expressions of
      cytokines implicated in microvascular leakage, endothelial repair, and pro
      inflammatory immune responses, and a network periphery consisting of a mixture of
      MSF and DEBONEL patients with relatively lower overall cytokine expressions.
      These results provide evidence of pathways triggered by rickettsiae in humans,
      and a testable hypothesis for the mechanisms in a rickettsia-induced cytokine
      storm with the translational goal of identifying therapeutic targets. 

PMID- 24303288
TI  - Outlier Detection through Bipartite Visual Analytics.
AB  - A critical goal of outlier detection is to determine whether an outlying value
      was caused by experimental/human error, or by natural biological diversity.
      However, because univariate or multivariate methods (e.g., box plots and
      principle component analysis) typically used for outlier detection use unipartite
      representations, they cannot distinguish whether outliers across a set of
      variables represent, for example, a single patient or different patients. Here we
      propose a bipartite visual analytical approach to outlier detection, and
      demonstrate its usefulness for identifying complex bipartite outliers in a
      dataset of rickettsioses patients, which enabled domain experts to determine
      whether the outliers were caused by errors, or by biological diversity. 

PMID- 24303289
TI  - A probabilistic model of functional brain connectivity network for discovering
      novel biomarkers.
AB  - Graph theoretical analyses of functional brain connectivity networks have been
      limited to a static view of brain activities over the entire timeseries. In this
      paper, we propose a new probabilistic model of the functional brain connectivity
      network, the strong-edge model, which incorporates the temporal fluctuation of
      neurodynamics. We also introduce a systematic approach to identifying biomarkers
      based on network characteristics that quantitatively describe the organization of
      the brain network. The evaluation results of the proposed strong-edge network
      model is quite promising. The biomarkers derived from the strong-edge model have
      achieved much higher prediction accuracy of 89% (ROCAUC: 0.96) in distinguishing
      depression subjects from healthy controls in comparison with the conventional
      network model (accuracy: 76%, ROC-AUC: 0.87). These novel biomarkers have the
      high potential of being applied clinically in diagnosing neurological and
      psychiatric brain diseases with noninvasive neuroimaging technologies. 

PMID- 24303290
TI  - Genome and proteome annotation using automatically recognized concepts and
      functional networks.
AB  - Many tools have been developed for prediction of the function or disease
      association of genes and proteins, and this continues to be a highly active area
      of bioinformatics research. Typically, these methods predict which concepts
      should be annotated to genes or proteins, using terms from ontologies such as
      Gene Ontology (GO), largely overlooking other ontologies that are available.
      Here, we set out to broadly evaluate novel, automatically retrieved, gene-term
      annotations and identify those concepts of publicly available ontologies that can
      be predicted using a generalized tool for prediction of annotations. We
      identified terms that perform better than expected by chance using randomly
      generated gene sets and show that both manually curated terms in GO and
      automatically recognized terms can be used to develop reasonable predictive
      models. In all, we characterize terms in over 250 ontologies and identify more
      than 127,000 statistically significant terms that can be predicted on human
      genes. 

PMID- 24303291
TI  - clearScience: Infrastructure for Communicating Data-Intensive Science.
AB  - Progress in biomedical research requires effective scientific communication to
      one's peers and to the public. Current research routinely encompasses large
      datasets and complex analytic processes, and the constraints of traditional
      journal formats limit useful transmission of these elements. We are constructing
      a framework through which authors can not only provide the narrative of what was
      done, but the primary and derivative data, the source code, the compute
      environment, and web-accessible virtual machines. This infrastructure allows
      authors to "hand their machine"- prepopulated with libraries, data, and code-to
      those interested in reviewing or building off of their work. This project,
      "clearScience," seeks to provide an integrated system that accommodates the ad
      hoc nature of discovery in the data-intensive sciences and seamless transitions
      from working to reporting. We demonstrate that rather than merely describing the
      science being reported, one can deliver the science itself. 

PMID- 24303292
TI  - Toward semantic modeling of pharmacogenomic knowledge for clinical and
      translational decision support.
AB  - The purpose of this paper is to describe pilot work on a semantic model of the
      pharmacogenomics information found in drug product labels. The model's
      development is driven by a series of use cases that we have developed to
      demonstrate how structured pharmacogenomics information could be more effectively
      used to support clinical and translational efforts. Using an iterative process,
      the semantic model was field-tested by five pharmacists, who used it to manually
      annotate a subset of the sections that the Food and Drug Administration's Table
      of Pharmacogenomic Biomarkers in Drug Labels cites as containing pharmacogenomics
      information. The five pharmacists identified a total of 213 pharmacogenomics
      statements in 29 sections. The model showed the potential to make the
      unstructured pharmacogenomic information currently written in product labeling
      more accessible and actionable through structured annotations of pharmacogenomics
      effects and clinical recommendations. 

PMID- 24303293
TI  - Analyzing disease-associated protein structures with visual analytics.
AB  - Protein function is related to protein structure, and understanding disease
      associated structural changes is critical both to understanding protein-mediated
      illness and to developing clinical therapies. We have developed a visual
      analytics tool called ContactWalker that uses molecular dynamics simulations to
      investigate the structural and physical differences between wild type and disease
      associated protein structures. This tool has been used successfully to
      characterize the effects of the disease ataxia with vitamin E deficiency (AVED).
      We are now beginning to investigate mutations to other disease-associated
      proteins including the tumor suppressor protein p53. 

PMID- 24303295
TI  - Autworks: a cross-disease analysis application for Autism and related disorders.

PMID- 24303294
TI  - SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating
      Systems Biology Studies of Disorders of Military Relevance.
AB  - SysBioCube is an integrated data warehouse and analysis platform for experimental
      data relating to diseases of military relevance developed for the US Army Medical
      Research and Materiel Command Systems Biology Enterprise (SBE). It brings
      together, under a single database environment, pathophysio-, psychological,
      molecular and biochemical data from mouse models of post-traumatic stress
      disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will
      organize, centralize and normalize this data and provide an access portal for
      subsequent analysis to the SBE. It provides new or expanded browsing, querying
      and visualization to provide better understanding of the systems biology of PTSD,
      all brought about through the integrated environment. We employ Oracle database
      technology to store the data using an integrated hierarchical database schema
      design. The web interface provides researchers with systematic information and
      option to interrogate the profiles of pan-omics component across different data
      types, experimental designs and other covariates. 

PMID- 24303296
TI  - Categorizing medications from unstructured clinical notes.
AB  - One of the important pieces of information in a patient's clinical record is the
      information about their medications. Besides administering information, it also
      consists of the category of the medication i.e. whether the patient was taking
      these medications at Home, were administered in the Emergency Department, during
      course of stay or on discharge etc. Unfortunately, much of this information is
      presently embedded in unstructured clinical notes e.g. in ER records, History &
      Physical documents etc. This information is required for adherence to quality and
      regulatory guidelines or for retrospective analysis e.g. CMS reporting. It is a
      manually intensive process to extract such information. This paper explains in
      detail a statistical NLP system developed to extract such information. We have
      trained a Maximum Entropy Markov model to categorize instances of medication
      names into previously defined categories. The system was tested on a variety of
      clinical notes from different institutions and we achieved an average accuracy of
      91.3%. 

PMID- 24303297
TI  - An empirical workflow for genome-wide single nucleotide polymorphism-based
      predictive modeling.
AB  - Technology is constantly evolving, necessitating the development of workflows for
      efficient use of high-dimensional data. We develop and test an empirical workflow
      for predictive modeling based on single nucleotide polymorphisms (SNP) from
      genome-wide association study (GWAS) datasets. To this aim, we use as a case
      study SNP-based prediction of survival for non-small cell lung cancer (NSCLC)
      with a Bayesian rule learner system (BRL+). Lung cancer is a leading cause of
      mortality. Standard treatment for early stages of NSCLC is surgery. Adjuvant
      chemotherapy would be beneficial for patients with early recurrence;
      consequently, we need models capable of such prediction. This workflow outlines
      the challenges involved in processing GWAS datasets from one popular platform
      (Affymetrix(r)), from the results files of the hybridization experiment to the
      model construction. Our results show that our workflow is feasible and efficient
      for processing such data while also yielding SNP based models with high
      predictive accuracy over cross validation. 

PMID- 24303298
TI  - Educating translational researchers in research informatics principles and
      methods: an evaluation of a model online course and plans for its dissemination.
AB  - Translational research generates and/or uses very large amounts of diverse data.
      Informatics principles and methods address datasets that are large and complex,
      whereas few translational researchers know these principles and methods and many
      cannot design, carry out, or analyze the results of these studies optimally. With
      few exceptions, informatics education has not been directed to researchers,
      especially established researchers. To fill this gap, we carried out a formal
      needs assessment of research informatics education of translational researchers,
      focusing on established researchers. Using the results, we developed a model
      curriculum for educating researchers in research informatics and a first
      generation model online course in research informatics for researchers. We are
      completing a formal evaluation of this online course with a diverse group of
      translational researchers. From the results of this evaluation, we will create a
      second version of the online course, a dissemination plan to make it available to
      researchers nationally, and a plan to enhance the course over time. We will
      discuss the implications for the future of translational research and research
      informatics. 

PMID- 24303299
TI  - Development of a scalable pharmacogenomic clinical decision support service.
AB  - Advances in sequencing technology are making genomic data more accessible within
      the healthcare environment. Published pharmacogenetic guidelines attempt to
      provide a clinical context for specific genomic variants; however, the actual
      implementation to convert genomic data into a clinical report integrated within
      an electronic medical record system is a major challenge for any hospital. We
      created a two-part solution that integrates with the medical record system and
      converts genetic variant results into an interpreted clinical report based on
      published guidelines. We successfully developed a scalable infrastructure to
      support TPMT genetic testing and are currently testing approximately two
      individuals per week in our production version. We plan to release an online
      variant to clinical interpretation reporting system in order to facilitate
      translation of pharmacogenetic information into clinical practice. 

PMID- 24303300
TI  - Qualitative and quantitative image-based biomarkers of therapeutic response in
      triple-negative breast cancer.
AB  - Experimental targeted treatments for neoadjuvant chemotherapy for triple-negative
      breast cancer are currently underway, and a current challenge is predicting which
      patients will respond to these therapies. In this study, we use data from dynamic
      contrast-enhanced MRI (DCE-MRI) images to predict whether patients with triple
      negative breast cancer will respond to an experimental neoadjuvant chemotherapy
      regimen. Using pre-therapy image-based features that are both qualitative (e.g.,
      morphological BI-RADS categories) and quantitative (e.g., lesion texture), we
      built a model that was able to predict whether patients will have residual
      invasive cancer with lymph nodes metastases following therapy (receiver operating
      characteristic area under the curve of 0.83, sensitivity=0.73, specificity=0.83).
      This model's performance is at a level that is potentially clinically valuable
      for predicting which patients may or may not benefit from similar treatments in
      the future. 

PMID- 24303301
TI  - Extending the "web of drug identity" with knowledge extracted from United States
      product labels.
AB  - Structured Product Labels (SPLs) contain information about drugs that can be
      valuable to clinical and translational research, especially if it can be linked
      to other sources that provide data about drug targets, chemical properties,
      interactions, and biological pathways. Unfortunately, SPLs currently provide
      coarsely-structured drug information and lack the detailed annotation that is
      required to support computational use cases. To help address this issue we
      created LinkedSPLs, a Linked Data resource that extends the "web of drug
      identity" using information extracted from SPLs. In this paper we describe the
      mapping that LinkedSPLs provides between SPL active ingredients and DrugBank
      chemical entities. These mappings were created using three approaches: InChI
      chemical structure descriptors comparison, exact string matching based on the
      chemical name, and automatic (unsupervised) linkage identification. Comparison of
      the approaches found that, while these three approaches are complementary, the
      automatic approach performs well in terms of precision and recall. 

PMID- 24303302
TI  - The Stem Cell Commons: an exemplar for data integration in the biomedical domain
      driven by the ISA framework.
AB  - Comparisons of stem cell experiments at both molecular and semantic levels remain
      challenging due to inconsistencies in results, data formats, and descriptions
      among biomedical research discoveries. The Harvard Stem Cell Institute (HSCI) has
      created the Stem Cell Commons (stemcellcommons.org), an open, community-based
      approach to data sharing. Experimental information is integrated using the
      Investigation-Study-Assay tabular format (ISA-Tab) used by over 30 organizations
      (ISA Commons, isacommons.org). The early adoption of this format permitted the
      novel integration of three independent systems to facilitate stem cell data
      storage, exchange and analysis: the Blood Genomics Repository, the Stem Cell
      Discovery Engine, and the new Refinery platform that links the Galaxy analytical
      engine to data repositories. 

PMID- 24303303
TI  - Providing pharmacogenomics clinical decision support using whole genome
      sequencing data as input.
AB  - Pharmacogenomics(PGx) is believed to be the driver for adopting pre-emptive
      clinical genetic testing. We investigated two potential resources for enabling
      automated pharmacogenomic decision support. First, we analyzed pharmacogenomics
      dosing guidelines (PDGs) and how they might be executed to provide alerts for
      clinicians ordering drugs. Second, we use whole genome sequencing (WGS) data
      instead of genotyping arrays to obtain patients' genetic profiles. In a pilot
      study, we attempted to generate clinical recommendations (based on PDGs) for 69
      patients whose genomes were obtained from a public data set provided by Compete
      Genomics. We report on the generated recommendations and the additional
      variations detected by WGS that are not well addressed by existing guidelines. 

PMID- 24303304
TI  - Harvest: a web-based biomedical data discovery and reporting application
      development platform.
AB  - Biomedical researchers share a common challenge of making complex data
      understandable and accessible. This need is increasingly acute as investigators
      seek opportunities for discovery amidst an exponential growth in the volume and
      complexity of laboratory and clinical data. To address this need, we developed
      Harvest, an open source framework that provides a set of modular components to
      aid the rapid development and deployment of custom data discovery software
      applications. Harvest incorporates visual representations of multidimensional
      data types in an intuitive, web-based interface that promotes a real-time,
      iterative approach to exploring complex clinical and experimental data. The
      Harvest architecture capitalizes on standards-based, open source technologies to
      address multiple functional needs critical to a research and development
      environment, including domain-specific data modeling, abstraction of complex data
      models, and a customizable web client. 

PMID- 24303305
TI  - Learning signals of adverse drug-drug interactions from the unstructured text of
      electronic health records.
AB  - Drug-drug interactions (DDI) account for 30% of all adverse drug reactions, which
      are the fourth leading cause of death in the US. Current methods for post
      marketing surveillance primarily use spontaneous reporting systems for learning
      DDI signals and validate their signals using the structured portions of
      Electronic Health Records (EHRs). We demonstrate a fast, annotation-based
      approach, which uses standard odds ratios for identifying signals of DDIs from
      the textual portion of EHRs directly and which, to our knowledge, is the first
      effort of its kind. We developed a gold standard of 1,120 DDIs spanning 14
      adverse events and 1,164 drugs. Our evaluations on this gold standard using
      millions of clinical notes from the Stanford Hospital confirm that identifying
      DDI signals from clinical text is feasible (AUROC=81.5%). We conclude that the
      text in EHRs contain valuable information for learning DDI signals and has
      enormous utility in drug surveillance and clinical decision support. 

PMID- 24303306
TI  - A Framework of Knowledge Integration and Discovery for Supporting
      Pharmacogenomics Target Predication of Adverse Drug Events: A Case Study of Drug
      Induced Long QT Syndrome.
AB  - Knowledge-driven text mining is becoming an important research area for
      identifying pharmacogenomics target genes. However, few of such studies have been
      focused on the pharmacogenomics targets of adverse drug events (ADEs). The
      objective of the present study is to build a framework of knowledge integration
      and discovery that aims to support pharmacogenomics target predication of ADEs.
      We integrate a semantically annotated literature corpus Semantic MEDLINE with a
      semantically coded ADE knowledgebase known as ADEpedia using a semantic web based
      framework. We developed a knowledge discovery approach combining a network
      analysis of a protein-protein interaction (PPI) network and a gene functional
      classification approach. We performed a case study of drug-induced long QT
      syndrome for demonstrating the usefulness of the framework in predicting
      potential pharmacogenomics targets of ADEs. 

PMID- 24303307
TI  - Adoption of Research Networking Systems in the Clinical and Translational Science
      Award (CTSA) Consortium.
AB  - Research Networking Systems (RNSs) have been of substantial interest for large
      research organizations as a means of fostering collaboration and increasing the
      visibility of individual investigators. A survey of the CTSA consortium assessed
      the state of first generation RNS adoption by member institutions. The survey
      queried the level of research networking adoption, system diversity,
      implementation maturity, data sources, use of Linked Open Data (LOD) and the VIVO
      core ontology, resources required, and individuals and roles profiled. Sixty-one
      CTSA-funded institutions were contacted and yielded a 75% response rate. The
      results demonstrate the extent of adoption of Research Networking Recommendations
      approved by the CTSA Consortium Executive and Steering Committee in October 2011.

PMID- 24303308
TI  - Automated Detection of Systematic Off-label Drug Use in Free Text of Electronic
      Medical Records.
AB  - Off-label use of a drug occurs when it is used in a manner that deviates from its
      FDA label. Studies estimate that 21% of prescriptions are off-label, with only
      27% of those uses supported by evidence of safety and efficacy. We have developed
      methods to detect population level off-label usage using computationally
      efficient annotation of free text from clinical notes to generate features
      encoding empirical information about drug-disease mentions. By including
      additional features encoding prior knowledge about drugs, diseases, and known
      usage, we trained a highly accurate predictive model that was used to detect
      novel candidate off-label usages in a very large clinical corpus. We show that
      the candidate uses are plausible and can be prioritized for further analysis in
      terms of safety and efficacy. 

PMID- 24303309
TI  - Genetic Networks of Complex Disorders: from a Novel Search Engine for PubMed
      Article Database.
AB  - Finding genetic risk factors of complex disorders may involve reviewing hundreds
      of genes or thousands of research articles iteratively, but few tools have been
      available to facilitate this procedure. In this work, we built a novel
      publication search engine that can identify target-disorder specific, genetics
      oriented research articles and extract the genes with significant results.
      Preliminary test results showed that the output of this engine has better
      coverage in terms of genes or publications, than other existing applications. We
      consider it as an essential tool for understanding genetic networks of complex
      disorders. 

PMID- 24303310
TI  - Order-disorder interface characterization reveals critical factors for disease
      and drug targets.
AB  - Signal transduction pathways are of critical importance in disease and regulation
      of cellular functions. Proteins that do not fold to a state of stable tertiary
      structure, known as intrinsically disordered proteins, are highly represented in
      signaling pathways and protein interaction networks. Important examples of
      disordered signaling proteins include p53 and BRCA1, and approximately 40% of
      Eukaryotic proteins are estimated to have significant disordered regions. Certain
      regions within these disordered proteins, however, can take on an ordered
      structure upon binding to a partner. The nature of the resulting protein-protein
      interactions has not yet been established. Here we categorize and identify
      interactions between binding segments of disordered proteins and their ordered
      partners using a Bayesian network framework, constructed on a test set of 964
      proteins mined for Molecular Recognition Feature (MoRF) characteristics from the
      PDB. This framework, more specifically Bayesian network learning, enables us to
      investigate the underlying biological processes involved, including the
      sequential and structural determinants of these interactions. After the
      construction of the training set (80% of data), features were successively
      eliminated to determine relative significances. The Bayesian network model was
      validated on the test set with excellent accuracy(>90% AUC). Examining features
      underlying the model provides a plethora of new and potentially useful biological
      information. The results also lend themselves to a strategy for rational drug
      design whereby disordered regions can be targeted with a high degree of
      specificity and small molecule peptide mimetics of their binding regions can be
      utilized as drugs. 

PMID- 24303311
TI  - Galaxy High Throughput Genotyping Pipeline for GeneTitan.
AB  - Latest genotyping solutions allow for rapid testing of more than two million
      markers in one experiment. Fully automated instruments such as Affymetrix
      GeneTitan enable processing of large numbers of samples in a truly high
      throughput manner. In concert with solutions like Axiom, fully customizable array
      plates can now utilize automated workflows that can leverage multi-channel
      instrumentation like the GeneTitan. With the growing size of raw data output, the
      serial computational architecture of the software, typically distributed by the
      vendors on turnkey desktop solutions for quality control and genotype calling,
      becomes legacy rather than an advantage. Advanced software techniques provide
      power, flexibility, and can be deployed in an HPC environment, but become
      technically inconvenient for biologists to use. Here we present a pipeline that
      uses Galaxy as a mechanism to lower the barrier for complex analysis, and
      increase efficiency by leveraging high-throughput computing. 

PMID- 24303312
TI  - Development of an open-source, flexible framework for complex inter-institutional
      disparate data sharing and collaboration.
AB  - Clinical information, "-omic" datasets, and tissue samples are difficult to
      harmonize and manage for data mining. We have developed a platform for storing
      clinical research data while providing access to associated data from other
      information stores. Data on 34 metrics from 11,000 neuroblastoma patients were
      instantiated into a database. The Django web framework was used to create a model
      for rapid development of tools and views with a front-end interface for
      generating complex queries. Working with Nationwide Children's Hospital, we can
      now consume their tissue inventory data through an API. The end-user sees the
      number of patients who both match their search and have tissue available. Since
      initial implementation, the current tasks revolve around developing a governance
      structure and the necessary data use agreements. Efforts now are to (1) update
      the data with 5000 more patients, and (2) link to genomic data stores,
      facilitating disparate data acquisition for research studies. 

PMID- 24303313
TI  - Robust prediction-based analysis for genome-wide association and expression
      studies.
AB  - Here we describe a prediction-based framework to analyze omic data and generate
      models for both disease diagnosis and identification of cellular pathways which
      are significant in complex diseases. Our framework differs from previous analysis
      in its use of underlying biology (cellular pathways/gene-sets) to produce
      predictive feature-disease models. In our study of alcoholism, lung cancer, and
      schizophrenia, we demonstrate the framework's ability to robustly analyze omic
      data of multiple types and sources, identify significant features sets, and
      produce accurate predictive models. 

PMID- 24303314
TI  - Scalable Data-driven Phenotypes via Unsupervised Feature Learning.
AB  - Inferring precise phenotypic patterns from population-scale clinical data is a
      critical computational task of personalized medicine. The dominant approach uses
      supervised learning, in which a human expert specifies which patterns to look for
      (by designating a learning task and class labels) and where to look for them (by
      constructing input features). This scales poorly and misses the unexpected
      patterns, which are the most informative. Unsupervised feature learning overcomes
      these limitations by identifying patterns (or features) that form a compact,
      expressive representation of their source data without depending on class labels
      or human input. Unsupervised features have become the state of the art for image
      and speech recognition. In this work we introduce the idea of using them for the
      problem of phenotype recognition. We present an unsupervised approach for
      inferring broadly useful, data-driven micro-phenotypes in the form of continuous,
      longitudinal features learned from noisy, sparse, and irregular EMR data. In our
      demonstration project, unsupervised features learned from longitudinal laboratory
      values were as accurate (0.96 AUC) in a classification task unknown to the
      learning algorithm as gold-standard features engineered by an expert with
      complete knowledge of the domain, the data, and the class labels. 

PMID- 24303315
TI  - Pharmacovigilance using Clinical Text.
AB  - The current state of the art in post-marketing drug surveillance utilizes
      voluntarily submitted reports of suspected adverse drug reactions. We present
      data mining methods that transform unstructured patient notes taken by doctors,
      nurses and other clinicians into a de-identified, temporally ordered, patient
      feature matrix using standardized medical terminologies. We demonstrate how to
      use the resulting high-throughput data to monitor for adverse drug events based
      on the clinical notes in the EHR. 

PMID- 24303316
TI  - Standardizing Phenotype Variables in the Database of Genotypes and phenotypes
      (dbGaP) based on Information Models.
AB  - This paper describes an information model based approach to standardizing
      phenotype variables in dbGaP. Our attempt to utilize existing information models
      of Clinical Element Models (CEM) was not successful although CEM provided a
      robust means of representing clinical data. Thus, we developed information models
      derived from phenotype variable descriptions and standardized phenotype variables
      by fitting them into the models using a simple Natural Language Processing (NLP)
      algorithm. We report the experience of standardizing findings related variables,
      which tend to be more idiosyncratic thus pose more challenges to standardization,
      using this approach. 

PMID- 24303317
TI  - Mining patterns of adverse events using aggregated clinical trial results.
AB  - Adverse event reports contain the most important metrics for evaluating the
      hazards, harms, and risks of a clinical intervention. In this paper, we present
      an exploratory study of discovering internal association patterns between adverse
      events. By taking advantage of the published trials reports on
      ClinicalTrials.gov, we developed an automatic pipeline to create a Clinical Trial
      Adverse Event Database (cTAED), which currently stores 4,317 clinical trial
      reports and 11,362 adverse events. The association mining algorithm FP-Tree was
      applied to the cTAED data to discover patterns between adverse events. We
      extracted 29,546 patterns and further examined association patterns related to
      patients' deaths. The mined results indicate the existence of strong internal
      association patterns between adverse events. The evaluation results show that the
      p-value of confidence is smaller than 0.001, which indicates that our method
      mined association patterns with significantly more confidence than randomly
      associated adverse events. 

PMID- 24303319
TI  - Analysis of sequence-based copy number variation detection tools for cancer
      studies.

PMID- 24303318
TI  - Platform for Personalized Oncology: Integrative analyses reveal novel molecular
      signatures associated with colorectal cancer relapse.
AB  - Approximately 80% of Stage II colon cancer patients are cured by appropriate
      surgery. However, 20% relapse, and virtually all of these people will die due to
      metastatic disease. Adjuvant chemotherapy has little or no impact on relapse or
      survival in Stage II colon cancer, and can only add toxicity without benefit for
      80% of the target population that has been cured by surgery. Despite much effort,
      it is difficult to identify clinical or molecular determinants of outcome in
      Stage II colon cancer, defeating attempts to target treatments to the 20% of
      individuals who are destined to relapse. We hypothesized that a multidimensional
      molecular analysis will identify a combination of factors that serve as
      prognostic biomarkers in Stage II adenocarcinoma of the colon. The Georgetown
      informatics team generated and analyzed multi-omics profiling datasets in stage
      II CRC patients with or without relapse to identify molecular signatures in CRC
      that may serve both as prognostic markers of recurrence, and also allow for
      identification of the subgroup of patients who might benefit from adjuvant
      chemotherapy. The datasets were loaded to GDOC(r) (Georgetown Database of Cancer)
      for further mining and analysis. The G-DOC web portal
      (http://gdoc.georgetown.edu) includes a broad collection of bioinformatics and
      systems biology tools for analysis and visualization of four major "omics" types:
      DNA, mRNA, microRNA, and metabolites. Through technology re-use, the G-DOC
      infrastructure will accelerate progress for a variety of ongoing programs in need
      of integrative multi-omics analysis, and advance our opportunities to practice
      effective personalized oncology in the near future. 

PMID- 24303320
TI  - Genomes in the cloud: balancing privacy rights and the public good.
AB  - The NIH-funded iDASH1 National Center for Biomedical Computing was created in
      2010 with the goal of developing infrastructure, algorithms, and tools to
      integrate Data for Analysis, 'anonymization,' and SHaring. iDASH is based on the
      premise that, while a strong case for not sharing information to preserve
      individual privacy can be made, an equally compelling case for sharing genome
      information for the public good (i.e., to support new discoveries that promote
      health or alleviate the burden of disease) should also be made. In fact, these
      cases do not need to be mutually exclusive: genome data sharing on a cloud does
      not necessarily have to compromise individual privacy, although current practices
      need significant improvement. So far, protection of subject data from re
      identification and misuse has been relying primarily on regulations such as
      HIPAA, the Common Rule, and GINA. However, protection of biometrics such as a
      genome requires specialized infrastructure and tools. 

PMID- 24303321
TI  - Evaluation considerations for EHR-based phenotyping algorithms: A case study for
      drug-induced liver injury.
AB  - Developing electronic health record (EHR) phenotyping algorithms involves
      generating queries that run across the EHR data repository. Algorithms are
      commonly assessed within demonstration studies. There remains, however, little
      emphasis on assessing the precision and accuracy of measurement methods during
      the evaluation process. Depending on the complexity of an algorithm, interim
      refinements may be required to improve measurement methods. Therefore, we develop
      an evaluation framework that incorporates both measurement and demonstration
      studies. We evaluate a baseline EHR phenotyping algorithm for drug induced liver
      injury (DILI) developed in collaboration with electronic Medical Records Genomics
      (eMERGE) network participants. We conduct a measurement study and report
      qualitative (i.e., perceptions of evaluation approach effectiveness) and
      quantitative (i.e., inter-rater reliability) measures. We also conduct a
      demonstration study and report qualitative (i.e., appropriateness of results) and
      quantitative (i.e., positive predictive value) measures. Given results from the
      measurement study, our evaluation approach underwent multiple changes including
      the addition of laboratory value visualization and an expanded review of clinical
      notes. Results from the demonstration study informed changes to our algorithm.
      For example, given the goal of eMERGE to identify patients who may have a genetic
      susceptibility to DILI, we excluded overdose patients. 

PMID- 24303322
TI  - Systematic identification of interaction effects between validated genome- and
      environment-wide associations on Type 2 Diabetes Mellitus.

PMID- 24303323
TI  - Domain landscapes of somatic mutations in cancer.
AB  - The fight against cancer has been hindered by its highly heterogeneous nature.
      Recent genome-wide sequencing studies have shown that individual malignancies
      contain many mutations that range from those commonly found in tumor genomes to
      rare cancer somatic mutations present only in a small fraction of lesions. For
      instance, the genome of a colorectal cancer in one patient can have somewhere
      between 50 to 100 somatic mutations, but might share only 2 or 3 mutated genes
      with colorectal tumor genomes from other patients. Somatic mutations that are
      frequently found in tumor genomes often play a significant role in tumor
      development and are thus classified as cancer driver mutations. However, efforts
      to correlate somatic mutations found in one or few individual tumor genomes with
      critical functional roles in tumor development have so far been unsuccessful. In
      this paper, we analyze cancer somatic mutations from lung and other types of
      cancer patients using a new approach based on aggregation of mutational data at
      the protein domain level. Our preliminary analysis confirms that our approach
      creates a framework for leveraging structural genomics and evolution into the
      analysis of somatic cancer mutations. We found that by incorporating information
      about classification of proteins and protein sites we are able to detect novel
      clusters of cancer somatic mutations. 

PMID- 24303324
TI  - Database integration of 4923 publicly-available samples of breast cancer
      molecular and clinical data.
AB  - We outline a paradigm for meta-microarray database creation and integration with
      clinical variables. We use as our implementation example a breast cancer database
      linking RNA expression measurements (by microarray) and clinical variables, such
      as survival metrics and tumor size. Such an endeavor involves integrating across
      different microarray datasets as well as clinical parameters. To this end, we
      created a data curation and processing pipeline, formal database ontology, and
      SQL schema to optimally query, analyze and visualize data from over 30 publicly
      available breast cancer microarray studies listed in the Gene Expression Omnibus
      (GEO). We demonstrate several pilot examples using this database. This
      methodology serves as a model for future meta-analyses of complex public clinical
      datasets, in particular those in the field of cancer. 

PMID- 24303325
TI  - Anonymous Record Linkage Between EPR and CDW-H: Toward Development of a Federated
      Genotype-Phenotype System.
AB  - Environmental Polymorphisms Registry (EPR) is a large-scale phenotype-by-genotype
      registry developed by National Institute of Environmental Health Sciences to
      facilitate translational research. The link between personal identity and
      collected genomic data was preserved in EPR which creates opportunities for EPR
      to be linked to phenotype-rich databases, such as the Carolina Data Warehouse for
      Health (CDW-H) located at the University of North Carolina hospital system. CDW-H
      contains clinically-relevant data for patients who have been admitted to UNC
      healthcare system. To validate the feasibility of linking EPR with CDWH, the
      number of matching records between the two databases had to be established. To
      that end, combinations of subjects' demographic identifiers from both databases
      were converted to anonymized hash codes, which were then matched to determine the
      number of overlapping records. Preliminary results showed that combination of
      last name, gender, data of birth and zip code would generate over 2,700 matches
      between the two databases. 

PMID- 24303326
TI  - Using Systems Biology-based Analysis Approaches to Identify Mechanistically
      Significant Adverse Drug Reactions: Pulmonary Complications from Combined Use of
      Anti-TNFalpha Agents and Corticosteroids.
AB  - Anti-TNF drugs are frequently associated with serious Adverse Events (AEs), which
      necessitates an improved understanding of individual factors that determine
      efficacy and safety of anti-TNF agents. We mined the US FDA's Adverse Event
      Reporting System (AERS) for anti-TNF-associated AEs to identify and stratify
      patient subgroups and drug combinations that exhibit specifically correlated
      complications. We demonstrate the existence of patient subgroup and anti-TNF
      agent-specific associations for relative risks of developing known and novel AEs
      including infections, edema, and organ damage associated processes. Concomitant
      use of anti-TNFs with corticosteroids significantly increased risk of AEs (p <
      0.001) including pulmonary fibrosis and pulmonary edema. Using these tightly
      correlated phenotypes, we mined mouse phenotype data to identify the molecular
      basis of these AEs. Multiple pathways and networks that regulate injury response,
      fluid regulation, and wound healing were implicated suggesting modification of
      anti-TNF-based therapeutic strategies to minimize corticosteroid-based
      combinatorial risk of severe AEs. 

PMID- 24303328
TI  - Drug repositioning from the combined evaluation of phenotypic and target-based
      screening.

PMID- 24303327
TI  - Clinical genomicist workstation.
AB  - The use of NextGen Sequencing clinically necessitates the need for informatics
      tools that support the complete workflow from sample accessioning to data
      analysis and reporting. To address this need we have developed Clinical
      Genomicist Workstation (CGW). CGW is a secure, n-tiered application where web
      browser submits requests to application servers that persist the data in a
      relational database. CGW is used by Washington University Genomic and Pathology
      Services for clinical genomic testing of many cancers. CGW has been used to
      accession, analyze and sign out over 409 cases since November, 2011. There are 22
      ordering oncologists and 7 clinical genomicists that use the CGW. In summary, CGW
      a 'soup-to-nuts' solution to track, analyze, interpret, and report clinical
      genomic diagnostic tests. 

PMID- 24303329
TI  - Panel: Alternative Careers for Biomedical Informatics PhDs.
AB  - The number of doctoral training programs in informatics increases every year,
      however not every doctoral candidate wishes to pursue a traditional career in
      academia. In addition, the knowledge and skills acquired through scientific
      training at the doctoral level can be valuable, even critical, for a number of
      career paths outside of academic research and teaching. This panel will present a
      diverse set of alternative career paths for which graduates of Informatics
      programs would be well suited, including patent law, research in industry,
      academic administration, and scientific journalism. Panelists will describe their
      own respective backgrounds and career paths, a day in the life in their current
      position, and how their training prepared them for their jobs. They will also
      touch on insights gained and lessons learned in exploring the professional
      landscape through non-traditional paths. 

PMID- 24303330
TI  - From EHRs to Linked Data: representing and mining encounter data for clinical
      expertise evaluation.
AB  - Translational science, today, involves multidisciplinary teams of scientists
      rather than single scientists. Teams facilitate biologically meaningful and
      clinically consequential breakthroughs. There are a myriad of sources of data
      about investigators, physicians, research resources, clinical encounters, and
      expertise to promote team interaction; however, much of this information is not
      connected and is left siloed. Large amounts of data have been published as Linked
      Data (LD), but there still remains a significant gap in the representation and
      connection of research resources and clinical expertise data. The CTSAconnect
      project addresses the problem of fragmentation and incompatible coding of
      information by creating a Semantic Framework that facilitates the production and
      consumption of LD about biomedical research resources, clinical activities, as
      well as investigator and physician expertise. 

PMID- 24303331
TI  - Network-based target ranking for polypharmacological therapies.
AB  - With the growing understanding of complex diseases, the focus of drug discovery
      has shifted from the well-accepted "one target, one drug" model designed towards
      a single target, to a new "multi-target, multidrug" model, aimed at systemically
      modulating multiple targets. In this context polypharmacology has emerged as a
      new paradigm to overcome the recent decline in pharmaceutical research and
      productivity. Likewise the networks are increasingly used as universal platforms
      to integrate the knowledge of a complex disease. A novel computational network
      based approach for the identification of multicomponent synergy is hereafter
      proposed. Given a complex disease, the method exploits the topological features
      of the related network to identify possible combinations of hit targets. The best
      ranked combinations are subsequently selected based on a synergistic score. The
      results obtained on Type 2 Diabetes Mellitus highlight the ability of the method
      to retrieve novel target candidates related to the considered disease. 

PMID- 24303332
TI  - New models of clinical discovery & science: progress and lessons learned the
      front lines of the dept. Of veterans' affairs transformational initiatives.

PMID- 24303333
TI  - Development of an ensemble resource linking MEDications to their Indications
      (MEDI).
AB  - Understanding of medications-disease relationships is critical to distinguish
      indications from adverse effects, and medication exposures serve as important
      markers of disease and severity in electronic medical records (EMR). We created a
      computable medication-indication (MEDI) resource by applying natural language
      processing and ontology relationships to four public medication resources.
      Physicians evaluated accuracy of medication-indication relationships. MEDI
      contained 3,112 medications and 63,343 medication-indication pairs derived from
      the four resources, whose precisions varied from 56-94%. The MEDI high precision
      subset (MEDI-HPS) includes indications found within either RxNorm or >=2
      resources and had an estimated precision of 92%. MEDI-HPS contains 13,304 unique
      indication pairs for 2,136 medications. MEDI is a free, computable resource that
      links medications with their indications as represented by formal concepts and
      may assist clinical and research uses of EMR data. 

PMID- 24303334
TI  - PharmGKB Drug Data Normalization with NDF-RT.
AB  - The Pharmacogenomics Knowledge Base (PharmGKB) [1] is a publicly available
      central resource for pharmacogenomics data and knowledge, which is being widely
      employed into clinical practice and thus requires using clinical terminologies.
      Hence, harmonizing PharmGKB drug data with well annotated drug terminologies will
      facilitate its integration with other related resources and support data
      representation, interpretation, and exchange within and across heterogeneous
      sources and applications. In this study, we extracted drug and drug class from
      PharmGKB, and mapped them to National Drug File Reference Terminology (NDF-RT)
      [2], which is integrated into RxNorm specified by U.S. Meaningful Use
      regulations. And the evaluated mapping results will be provided to PharmGKB for
      further investigation and collaboration. 

PMID- 24303335
TI  - Psychosocial Factors and Health-Risk Behaviors Associated with Hookah use among
      College Students.
AB  - INTRODUCTION: Prevalence of hookah or waterpipe smoking is increasing in the
      United States, particularly among college-aged students. Little research has
      examined the relationship between hookah smoking, other risk-seeking behaviors,
      and specific personality factors. The current study aims to address this gap in
      the literature. METHODS: A random sample of 10,000 students at two southeastern
      state universities were recruited to complete an online survey containing 230
      questions assessing sociodemographics, other substance use, and psychosocial
      factors. Of students invited to participate, 2,206 (22.1%) returned a completed
      survey. RESULTS: Past 30-day hookah use was found among 6.8% (n=141) of the
      sample. Binary logistic regression indicated that, after controlling for age,
      ethnicity, and highest parental education, hookah use was associated with being
      male (p<.001), being a nondaily or daily smoker versus a nonsmoker (p<.001), more
      frequent alcohol consumption (p<.001), greater sensation seeking (p<.001), lower
      levels of conscientiousness (p<.001), and greater openness to experiences
      (p=.01). CONCLUSIONS: Understanding the psychological and personality profiles of
      hookah users may allow public health practitioners and health care providers to
      identify high-risk individuals and design targeted interventions addressing users
      and those at risk for use.

PMID- 24303336
TI  - Embryonic Stem Cells: A Perfect Tool for Studying Mammalian Transcriptional
      Enhancers.
AB  - Transcriptional enhancers are DNA elements capable of regulating gene expression
      in-cis over great distances. With the recent availability of genomic approaches
      to define epigenetic marks and RNA levels, these previously difficult to study
      elements are now being extensively examined for their critical role in lineage
      specific transcriptional regulation. This review sets out to highlight the use of
      embryonic stem cells (ESCs) in the study of enhancers, emphasizing that ESC have
      become an ideal model system for questions regarding mammalian transcriptional
      regulation. This review highlights the epigenetic "signature" of enhancers, their
      mechanism of action, and the role of non-coding RNAs (ncRNAs) on enhancer
      function. We briefly review insulators, a sub-type of enhancers, and a novel
      model system for studying enhancer function in vivo. We conclude with some
      ongoing questions within the field.

PMID- 24303337
TI  - Effects of health on changing labor force participation in Pakistan.
AB  - ABSTRACT: The objective of the study investigates the effects of health on
      changing labor force participation during Pakistan's economic transition in the
      1980s, a period of several economic liberalization and international integration
      on the health and financial sectors. The study employed the autoregressive
      distributed lag (ARDL) co-integration technique to estimate the short- and long
      run elasticities, while the Wald coefficient restrictions tests was used to
      determine the dynamic short-run causality between the variables over a period of
      1975-2011. The study was limited to a few variables, including age dependency,
      health expenditures, trade openness, population per bed, life expectancy, gross
      capital formation, mortality rate, secondary school enrolment and labor force
      participation rate, in order to manage robust data analysis. The results suggest
      that infant mortality rate (IMR), gross capital formation (GCF) and secondary
      school enrolment (SSE) decrease the labor force participation rate in the long
      run, as if there is one percent increase IMR, GCF and SSE, labor force
      participation decreases by 0.653 percent, 0.137 percent and 0.220 percent
      respectively, however, these results invert the relationship in short-run. The
      study also finds that health expenditures has positive and significant impact on
      labor force participation rate in the short-run, but this result disappear in the
      long-run. Trade liberalization has a positive effect in the short run, while a
      negative effect is observed in the long run upon labor force participation rate
      of Pakistan. The study confirms that Pakistan did not enjoy substantial growth
      benefits related to health care because human capital (secondary school
      enrolment), trade openness, public investment and infant mortality rate have a
      negative impact on labor force participation rate. These findings have important
      policy implications. JEL CODES: H51, I21, J21.

PMID- 24303338
TI  - Impact of alternative approaches to assess outlying and influential observations
      on health care costs.
AB  - The distributions of medical costs are often skewed to the right because small
      numbers of patients use large amounts of health care resources. Using data from a
      study of colon cancer costs, we show, by example, the impact and magnitude of
      outliers and influential observations on health care costs and compared the
      effects of statistical costing methods for addressing the disproportionate
      influence of outliers and influential observations. We used data from a
      retrospective cohort study of 3,842 elderly veterans with colon cancer who were
      enrolled in and used health care from, both the Department of Veterans Affairs
      and Medicare in 1999-2004. After calculating the average colon cancer episode
      cost and distribution for the full cohort, we used box-plot methods,
      Winsorization, DFBETAs, and Cook's distance to identify and assess or adjust the
      outlying and/or influential observations. The number of observations identified
      as outlying and/or influential ranged from 13 when the predicted DFBETA
      measurement was greater than 0.15 and the observation was a qualified box-plot
      outlier to 384 cases using the Winsorization method at the 5th and 95th
      percentiles. Average costs of colon cancer episodes using these methods were
      similar. The method of choice from the results of this particular analysis can be
      conditionally based on whether the purpose is to control only for influential
      observations or to simultaneously control for outliers and influential
      observations. Understanding how estimates could change with each approach is
      important in assessing the impact of a particular method on the results. 

PMID- 24303339
TI  - Anthocyanin-rich Aronia melanocarpa extract improves body temperature maintenance
      in healthy women with a cold constitution.
AB  - PURPOSE: Specific anthocyanin-rich dietary factors have been shown to improve
      metabolic functions associated with thermogenesis in animal studies. Aronia
      melanocarpa, commonly known as wild chokeberry, contains a high level of
      anthocyanin that would be expected to maintain body temperature through
      thermogenesis. We here investigated the effects of Aronia melanocarpa extracts on
      body temperature and peripheral blood flow in healthy women with a cold
      constitution. METHODS: A pre/post comparison trial was performed in 11 women with
      a cold constitution, who were taking Aronia melanocarpa extracts (150 mg/day) for
      4 weeks. Physiological and biochemical parameters, along with psychological tests
      were examined. RESULTS: The subjects' body surface temperature was significantly
      higher in the post-trial than in the pre-trial. In psychological tests, factors
      related to cold were significantly improved by Aronia intake. On the other hand,
      peripheral blood flow was not affected by Aronia supplementation. Plasma
      noradrenalin level was significantly elevated by Aronia intake, and subjects with
      a higher level of 8-hydroxy-2'-deoxyguanosine in the pre-trial showed decreased
      levels in the post-trial. CONCLUSIONS: These data suggest that dietary Aronia
      melanocarpa extract improves the maintenance of body temperature in healthy women
      with a cold constitution, which may be mediated by noradrenalin and oxidative
      stress levels.

PMID- 24303340
TI  - Cropping practices, soil properties, pedotransfer functions and organic carbon
      storage at Kuanria canal command area in India.
AB  - Effects of cropping practices on soil properties viz. particle size distribution,
      pH, bulk density (BD), field capacity (FC, -33 kPa), permanent wilting point
      (PWP, -1500 kPa), available water capacity (AWC) and soil organic carbon (SOC)
      were assessed. The pedotransfer functions (PTFs) were developed for saturated
      hydraulic conductivity (Ks), water retention at FC and PWP of soils for different
      sites under major cropping system in a canal irrigated area. The results revealed
      that the soils are mainly composed of sand and clay with the clay contents
      ranging from 29.6 to 48.8%, BD of 1.44-1.72 Mg m(-3), and 0.34 to 0.95% SOC. The
      Ks decreased, and water retention at FC, PWP and AWC increased significantly with
      soil depth due to greater clay contents in lower soil depths. The PTFs were best
      represented as the power functions for prediction of Ks with clay content as
      predictor variable; whereas the PTFs for water retention at FC and PWP were
      better represented as the exponential functions. SOC content was higher under
      rice-sugarcane crop rotation compared to other systems. SOC storage in the
      surface layer was higher in rice-sugarcane rotation (18.90-20.53 Mg ha(-1)) than
      other sites. The developed PTFs would be very useful in soil and water management
      strategies for the study area or elsewhere having similar soil and cropping
      practices. The information on SOC storage in the Kuanria region would help for
      better soil and crop planning in future. 

PMID- 24303341
TI  - Densely calcified atypical choroid plexus papilloma at the cerebellopontine angle
      in an adult.
AB  - Choroid plexus papilloma is a rare benign tumor accounting for 0.5% of all
      intracranial tumors. The majority of choroid plexus papillomas occur during the
      first 2 years of life in the ventricular system. Moreover, dense calcification of
      the tumor is uncommon. We report an adult case of densely calcified, atypical
      choroid plexus papilloma that originated from the cerebellopontine angle without
      connection to the forth ventricle. Because the case involves a rare combination
      of four features-adult, dense calcification, atypical form, and cerebellopontine
      angle-each characteristic associated with the choroid plexus papilloma was
      discussed. The finding of calcification at the cerebellopontine angle in an adult
      should suggest the possible presence of choroid plexus papilloma. 

PMID- 24303342
TI  - Pathophysiology and treatment options in trigeminal meningoceles.
AB  - Trigeminal meningoceles, lateral to the maxillary nerve (V2), have seldom been
      reported as underlying pathology for spontaneous rhinoliquorrhea. In contrast to
      sphenoid meningoceles arising from a persistent lateral craniopharyngeal canal
      (Sternberg-Cruveilhier, medial to V2), their occurrence seems to be generated by
      addition of erosive processes to the constitutively thin bony shell underneath
      the semilunar ganglion, lateral to the round foramen (and V2). The developmental
      and anatomical relationships of trigeminal meningoceles to the sphenoid bone are
      depicted, and in a review of the literature we present the different surgical
      approaches employed for sealing the dura leak. In view of these techniques we
      discuss an unusual case of therapy-resistant rhinoliquorrhea with left-sided
      trigeminal meningocele involving the Meckel cave at the lateral sphenoid and
      reaching the superior orbital fissure and the medial orbital space. In contrast
      to patients who have lateral sphenoidal meningoceles with a persistent lateral
      craniopharyngeal canal (Sternberg-Cruveilhier), who can be treated successfully
      using an endoscopic transsphenoidal approach (recurrence rate 13.7%), the
      recurrence rate of cerebrospinal fluid (CSF) efflux for trigeminal meningoceles
      lies much higher (endoscopically 66%, open craniotomy 33%). The surgical strategy
      thus has to be chosen individually, taking into account specific anatomical
      situations and eventually preceding operations. 

PMID- 24303343
TI  - Transclival pseudomeningocele secondary to ecchordosis physaliphora: case report
      and literature review.
AB  - We describe a 52-year-old woman who presented with meningitis secondary to a
      pseudomeningocele within the sphenoid sinus derived from a bony defect in the
      clivus. The bony defect was radiologically characteristic of an ecchordosis
      physaliphora (EP). She underwent surgical repair of the defect and had resolution
      of her symptoms. This case report will discuss the second case of transclival
      pseudomeningocele in the English literature and present EP as a cause. 

PMID- 24303344
TI  - Cervical spinal canal stenosis and central disc herniation c3/4 in a man with
      primary complaint of thigh pain.
AB  - Purpose The purpose of this report is to describe the clinical course of a
      patient who had a primary complaint of isolated right lateral thigh pain 3 years
      prior that was nonresponsive to conservative measures. Hypoesthesia in the
      lateral side of the right forearm, deltoid and biceps, as well as triceps
      paresis, was also diagnosed. Results Immediately after surgery, the patient
      reported substantial improvement in his right thigh symptoms. The signs and
      symptoms associated with the right C6 and C7 radiculopathy did improve.
      Conclusion Although the presentation described in this case is somewhat unique,
      the eventual myelopathic signs and symptoms were not. It was these myelopathic
      signs and symptoms that led to cervical magnetic resonance imaging, the diagnosis
      of cervical cord compressive myelopathy, and surgical management. 

PMID- 24303345
TI  - Fibromyxoma of the lateral skull base in a child: case report.
AB  - Purpose Fibromyxomas and myxomas are benign tumors of mesenchymal origin usually
      found outside the nervous system, most commonly in the atrium of the heart. They
      can also arise in the mandible or maxilla, but it is exceedingly rare to find
      them within the skull base. The history, histologic features, and the literature,
      with emphasis on other pediatric cases, are reviewed for this uncommon skull base
      neoplasm. Methods We describe the case of a 13-year-old girl who presented with a
      1-year history of facial weakness, numbness, and hearing loss. A large locally
      destructive tumor centered in the petrous bone was found on magnetic resonance
      imaging. Results A mastoidectomy combined with a middle fossa craniotomy was
      performed for gross total resection. The child is disease free 12 months after
      surgery. Conclusion Diagnosis could not be made solely on radiographic studies
      because of the lack of pathognomonic imaging features. Radical resection provided
      the patient the best chance of cure. Long-term surveillance is necessary to
      monitor for tumor recurrence. 

PMID- 24303346
TI  - Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple
      Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base
      Ewing Sarcoma/PNET: Case Report.
AB  - Background Aneurysm formation after stereotactic irradiation of skull base tumors
      is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm
      in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor
      (PNET), who underwent surgery followed by multiple courses of intensity-modulated
      radiation therapy (IMRT) and chemotherapy, is described. Case Description A 25
      year-old man presented with a sinonasal tumor with intraorbital and intracranial
      growth. At that time cerebral angiography did not reveal any vascular
      abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was
      Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and
      three courses of IMRT at 3, 28, and 42 months after initial surgery. The total
      biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months
      after the third IMRT, the patient experienced profound nasal bleeding that
      resulted in hypovolemic shock. Angiography revealed a ruptured right C4-C5
      aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular
      trapping of the right ICA was done. The patient recovered well after surgery but
      died due to tumor recurrence 6 months later. Conclusion Excessive irradiation of
      the ICA may occasionally result in aneurysm formation, which should be borne in
      mind during stereotactic irradiation of malignant skull base tumors. 

PMID- 24303347
TI  - Advanced Image Coregistration within the Leksell Workstation for the Planning of
      Glioma Surgery: Initial Experience.
AB  - Background Leksell GammaPlan (LGP) and SurgiPlan (ELEKTA Instruments AB,
      Stockholm, Sweden) may be used effectively for the detailed evaluation of
      regional neuroanatomy before open neurosurgical procedures. We report our initial
      experience in the cases of cerebral gliomas. Methods LGP v.8.3 was used before
      the surgical resection of cerebral gliomas for (1) the delineation of subdural
      grid electrodes and a detailed evaluation of their position relatively to
      cortical structures, and (2) for the fusion of structural magnetic resonance
      imaging and diffusion tensor imaging (DTI) for a detailed visualization of the
      corticospinal tract (CST) and optic radiation. Results Delineation of the
      subdural grid within LGP in a patient with seizures caused by left parietal
      glioma permitted a detailed assessment of the location of electrodes relative to
      the cortical gyri and sulci and significantly facilitated interpretation of brain
      mapping before tumor resection. In another patient with parieto-occipital glioma,
      simultaneous three-dimensional visualization of the tumor, CST, and optic
      radiation with the use of LGP permitted us to perform tumor resection without
      postoperative neurologic complications. Finally, incorporation of DTI into
      SurgiPlan resulted in precise planning of stereotactic biopsy for bilateral
      thalamic glioma. Conclusion The possibility for detailed evaluation of regional
      neuroanatomy based on various images within LGP and SurgiPlan may facilitate
      effective and safe surgical management of intracranial gliomas. 

PMID- 24303348
TI  - No Association between Tumor Necrosis Factor-alpha Gene Polymorphisms and Lung
      Cancer Risk.
AB  - OBJECTIVES: The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF
      alpha) for lung cancer development was evaluated. METHODS: Genotypes of the TNF
      alpha polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G,
      were determined in 616 lung cancer cases and 616 lung cancer-free controls.
      RESULTS: After adjusting for body mass index and smoking, each TNF-alpha genotype
      or haplotype composed of five TNF-alpha single nucleotide polymorphisms did not
      show an association with lung cancer risk (p>0.05). The statistical power was
      found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G,
      IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP
      or haplotype on lung cancer risk were not found to be different according to the
      cell type of lung cancer (p>0.05). In the repeated analysis with only subjects
      without other diseases related to inflammation, there was also no association
      between polymorphisms or haplotypes of the TNF-alpha gene and lung cancer risk
      (p>0.05). CONCLUSIONS: This study found no association between common variants of
      the TNF-alpha gene and lung cancer risk.

PMID- 24303349
TI  - Ecological risk assessment of chemicals migrated from a recycled plastic product.
AB  - OBJECTIVES: Potential environmental risks caused by chemicals that could be
      released from a recycled plastic product were assessed using a screening risk
      assessment procedure for chemicals in recycled products. METHODS: Plastic slope
      protection blocks manufactured from recycled plastics were chosen as model
      recycled products. Ecological risks caused by four model chemicals -di-(2
      ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), cadmium (Cd), and lead
      (Pb)- were assessed. Two exposure models were built for soil below the block and
      a hypothetic stream receiving runoff water. Based on the predicted no-effect
      concentrations for the selected chemicals and exposure scenarios, the allowable
      leaching rates from and the allowable contents in the recycled plastic blocks
      were also derived. RESULTS: Environmental risks posed by slope protection blocks
      were much higher in the soil compartment than in the hypothetic stream. The
      allowable concentrations in leachate were 1.0*10(-4), 1.2*10(-5), 9.5*10(-3), and
      5.3*10(-3) mg/L for DEHP, DINP, Cd, and Pb, respectively. The allowable contents
      in the recycled products were 5.2*10(-3), 6.0*10(-4), 5.0*10(-1), and 2.7*10(-1)
      mg/kg for DEHP, DINP, Cd, and Pb, respectively. CONCLUSIONS: A systematic
      ecological risk assessment approach for slope protection blocks would be useful
      for regulatory decisions for setting the allowable emission rates of chemical
      contaminants, although the method needs refinement.

PMID- 24303350
TI  - Effects of Nano-sized Carbon Black on the Lungs of High Fat-diet Induced
      Overweight Rats.
AB  - OBJECTIVES: This study was conducted to determine whether nano-sized carbon black
      exposure results in greater damage in high fat diet-induced overweight rats than
      normal weight ones and to identify the possible causes of any differences.
      METHODS: Two groups of Sprague-Dawley rats allocated by body weight (normal and
      overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a
      day, 5 days per week over a 4-week period. Differential cell counts, lactate
      dehydrogenase (LDH) activities and albumin concentrations were measured in
      bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs
      were evaluated. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6
      were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated
      lymphocyte culture. RESULTS: Rats exposed to high concentrations of nano-sized
      carbon black showed significantly increased (p<0.05) polymorphonuclear leukocyte
      number and LDH activity in the BAL fluid from both overweight and normal rats.
      Mild histopathological changes were observed in normal rats irrespective of
      carbon black concentrations. However, severe histological scores were found in
      overweight rats (1.75+/-0.46, 2.25+/-0.46, and 2.88+/-0.35 after low, medium, and
      high concentration exposures). Proinflammatory cytokine levels of TNF-alpha and
      IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes
      of overweight rats, whereas there was no significant difference in the BAL fluid
      between normal and overweight rats. CONCLUSIONS: Inflammation and damage to lungs
      exposed to nano-sized carbon black was more severe in high fat diet-induced
      overweight rats compared to normal rats.

PMID- 24303351
TI  - Association between Low-level Mercury Exposure and Neurobehavioral Functions in
      Korean Adults Living in a Coastal City.
AB  - OBJECTIVES: The aim of this study was to determine the association between low
      level mercury exposure and neurobehavioral functions in adults living in coastal
      regions of Korea. METHODS: We selected 172 adults aged 20-65 years living in a
      city in the coastal region of Korea. A sociodemographic survey was conducted,
      mercury levels in the blood, urine, and hair were measured, and the associations
      according to computerized neurobehavioral tests were determined using univariate
      analysis. After adjustment for associated variables, a multivariate linear
      regression analysis was performed. RESULTS: The geometric mean mercury levels in
      the blood, urine, and hair were 5.41 ug/L (range, 0.00-15.84 ug/L), 1.17 ug/g
      creatinine (range, 0.00-32.86 ug/g-creatinine), and 1.37 mg/kg (range, 0.42-6.56
      mg/kg), respectively. Variables that were associated with simple reaction time
      according to the neurobehavioral test results were age and urine mercury level.
      Variables associated with choice reaction time were the recent use of Korean
      traditional medicine and urine mercury level. Variables associated with the right
      hand finger tapping speed test were age, gender, smoking behavior, education
      level, monthly household income, and urine mercury level. Variables associated
      with the left-hand finger tapping speed test were age, gender, education level,
      and urine mercury level. After adjustment for associated variables, there was no
      significant association between urine mercury level and simple reaction time
      (beta=25.96; p=0.47), choice reaction time (beta=50.37; p=0.32), or the number of
      left-hand finger taps (beta=-1.54; p=0.21). However, urine mercury level was
      significantly associated with the number of right-hand finger taps (beta=-3.86;
      p=0.01). CONCLUSIONS: We found no evidence that low-level mercury exposure in
      adults is associated with deficits in neurobehavioral functions. A longer follow
      up study is required to confirm this conclusion.

PMID- 24303352
TI  - Cardiovascular effect of epinephrine in endodontic microsurgery: a review.
AB  - Epinephrine is one of the most widely-used vasoconstrictors in dental treatment
      including endodontic microsurgery. However, the systemic safety of epinephrine
      has been in debate for many years because of its potential risk to cause
      cardiovascular complications. The purpose of this review was to assess the
      cardiovascular effect of epinephrine use in endodontic microsurgery. Endodontic
      microsurgery directly applies epinephrine into the bone cavity, and the amount is
      reported to be much larger than other dental surgeries. Moreover, when
      considering that systemic potency of intraosseous application is reported to be
      comparable to intravenous application, the systemic influence of epinephrine
      could be increased in endodontic microsurgery. Besides, pre-existing
      cardiovascular complications or drug interactions can enhance its systemic
      influence, resulting in increased susceptibility to cardiovascular complications.
      Although clinical studies have not reported significant complications for
      patients without severe systemic complications, many epinephrine-induced
      emergency cases are warning the cardiovascular risk related with pre-existing
      systemic disease or drug interactions. Epinephrine is a dose-sensitive drug, and
      its hypersensitivity reaction can be fatal to patients when it is related to
      cardiovascular complications. Therefore, clinicians should recognize the risk,
      and the usage of pre-operative patient evaluation, dose control and patient
      monitoring are required to ensure patient's safety during endodontic
      microsurgery. 

PMID- 24303353
TI  - Enamel matrix derivative for replanted teeth in animal models: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To investigate the effect of enamel matrix derivative (EMD) on
      periodontal healing of replanted teeth in animal models. MATERIALS AND METHODS:
      The authors searched MEDLINE, PubMed, EMBASE, Cochrane Library, Web of Knowledge
      and Scopus for articles published up to Oct 2012. Animal studies in which EMD was
      applied in transplanted or replanted teeth with adequate controls and
      histological data were considered. Normal periodontal healing or root resorption
      determined by histology after EMD was applied in replanted teeth with adequate
      controls was used as outcome measures. The following search strategy was used:
      ('Emdogain' OR 'enamel matrix proteins' OR 'enamel matrix derivative') AND
      ('avulsion' OR 'transplantion' OR 'autotransplantation' OR 'replantation').
      RESULTS: Six animal studies were included in the final review. There was great
      heterogeneity in study design among included studies. Two studies with similar
      study designs were identified and analyzed by a meta-analysis. The pooled
      estimates showed a significantly higher normal healing and surface resorption and
      significantly less inflammatory and replacement resorption in EMD-treated groups
      compared with non-EMD-treated groups. CONCLUSIONS: With the limitations of this
      systematic review, the use of EMD led to greater normal periodontal healing and
      surface root resorption and less inflammatory and replacement root resorption in
      the presence of periodontal ligaments. However, no definite conclusion could be
      drawn with regard to the effect of EMD on periodontal healing and root resorption
      when no periodontal ligaments exist.

PMID- 24303354
TI  - A comparative evaluation of cytotoxicity of root canal sealers: an in vitro
      study.
AB  - OBJECTIVES: The objective of this in vitro study was to evaluate and compare the
      cytotoxicity of four different root canal sealers i.e. Apexit Plus (Ivoclar
      Vivadent), Endomethasone N (Septodont), AH-26 (Dentsply) and Pulpdent Root Canal
      Sealer (Pulpdent), on a mouse fibroblast cell line (L929). MATERIALS AND METHODS:
      Thirty two discs for each sealer (5 mm in diameter and 2 mm in height) were
      fabricated in Teflon mould. The sealer extraction was made in cell culture medium
      (Dulbecco's Modified Eagle's Medium, DMEM) using the ratio 1.25 cm(2)/mL between
      the surface of the sealer samples and the volume of medium in a shaker incubator.
      Extraction of each sealer was obtained at 24 hr, 7th day, 14th day, and one month
      of interval. These extracts were incubated with L929 cell line and 3-(4,5
      dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay was done. Two
      way ANOVA for interaction effects between sealer and time and Post-hoc multiple
      comparison using Tukey's test across all the 16 different groups were used for
      statistical analysis. RESULTS: Apexit Plus root canal sealer was significantly
      less toxic than other sealers (p < 0.05) and showed higher cellular growth than
      control. Endomethasone N showed mild cytotoxicity. AH-26 showed severe toxicity
      which became mild after one month while Pulpdent Root Canal Sealer showed severe
      to moderate toxicity. CONCLUSIONS: Apexit Plus was relatively biocompatible
      sealer as compared to other three sealers which were cytotoxic at their initial
      stages, however, they became biocompatible with time.

PMID- 24303355
TI  - Chlorhexidine gel associated with papain in pulp tissue dissolution.
AB  - OBJECTIVES: This study aimed to evaluate the capacity of 2% chlorhexidine gel
      associated with 8% papain gel in comparison with 5.25% sodium hypochlorite in
      bovine pulp tissue dissolution. MATERIALS AND METHODS: Ninety bovine pulps of
      standardized sizes were used and fragmented into 5-mm sizes. The fragments were
      removed from the root middle third region. They were divided into 6 experimental
      groups (n = 15), 1) 8% papain; 2) 2% chlorhexidine; 3) 2% chlorhexidine
      associated with 8% papain; 4) 0.9% saline solution; 5) 2.5% sodium hypochlorite;
      and 6) 5.25% sodium hypochlorite. The pulp fragments were weighed and put into
      immobile test tubes for dissolution for time intervals of 30, 60, 90, and 120
      min. RESULTS: The 5.25% sodium hypochlorite had greater dissolution potential
      than the pure papain, and when associated with chlorhexidine, both promoted
      greater dissolution than did the saline solution and 2% chlorhexidine groups (p <
      0.05). The 2.5% sodium hypochlorite promoted dissolution to a lesser extent than
      the groups with papain within a period of 30 min (p < 0.05), but, was comparable
      to the saline solution and chlorhexidine. After 120 min, the 2.5% and 5.25%
      sodium hypochlorite promoted dissolution of 100% of the pulp fragments, and
      papain, 61%, while chlorhexidine associated with papain and chlorhexidine alone
      dissolved only 55% and 3%, respectively. CONCLUSIONS: The 8% papain in gel, both
      alone and in association with chlorhexidine, was able to dissolve bovine pulp
      tissue, but to a lesser extent than did 5.25% sodium hypochlorite.

PMID- 24303356
TI  - Retentive strength of different intracanal posts in restorations of anterior
      primary teeth: an in vitro study.
AB  - OBJECTIVES: To determine the retentive strength and failure mode of undercut
      composite post, glass fiber post and polyethylene fiber post luted with flowable
      composite resin and resin-cement. MATERIALS AND METHODS: Coronal parts of 120
      primary canine teeth were sectioned and specimens were treated endodontically.
      The teeth were randomly divided into 6 groups (n = 20). Prepared root canals
      received intracanal retainers with a short composite post, undercut composite
      post, glass fiber post luted with flowable resin or resin-cement, and
      polyethylene fiber post luted with flowable resin or resin-cement. After crown
      reconstruction, samples were tested for retentive strength and failure mode.
      Statistical analysis was done with one-way ANOVA and Tukey tests (p < 0.05).
      RESULTS: There were statistically significant differences between groups (p =
      0.001). Mean bond strength in the undercut group was significantly greater than
      in the short composite post (p = 0.030), and the glass fiber post (p = 0.001) and
      the polyethylene fiber post group luted with resin-cement (p = 0.008). However,
      the differences between the undercut group and the groups with flowable composite
      as the luting agent were not significant (p = 0.068, p = 0.557). Adhesive failure
      was more frequent in the fiber post groups. CONCLUSIONS: Although the composite
      post with undercutting showed the greatest resistance to dislodgement, fiber
      posts cemented with flowable composite resin provided acceptable results in terms
      of retentive strength and fracture mode.

PMID- 24303357
TI  - Influence of operator's experience level on lifespan of the WaveOne Primary file
      in extracted teeth.
AB  - OBJECTIVES: The aim of this study was to assess the influence of operator
      experience level on the lifespan of the WaveOne Primary file (Dentsply Maillefer,
      Ballaigues, Switzerland) in extracted teeth. MATERIALS AND METHODS: Moderately
      curved canals of extracted maxillary and mandibular molars were randomly
      distributed into 2 groups: experienced and inexperienced operators. Ten files
      were allocated to each group (n = 10). Each canal was prepared until the working
      length was reached, and the same file was used to prepare additional canals until
      it separated. The number of canals prepared before file separation was recorded.
      The fragment length of each file was measured, and the location of the fragment
      in the canal was determined. Data were statistically analysed using the
      independent 2-sample t-test. RESULTS: The 2 operators prepared a total of 324
      moderately curved canals of maxillary and mandibular molars. There was no
      significant intergroup difference in the mean number of canals prepared (p =
      0.27). The average lifespan of the WaveOne Primary file was 17.1 and 15.3 canals,
      and the longest lifespan was 25 and 20 canals, when used by experienced and
      inexperienced operators, respectively. There were no statistically significant
      intergroup differences in separated fragment length and location. CONCLUSIONS:
      Within the limitations of this study, operator experience level appears to have
      no effect on the lifespan of the WaveOne Primary file in preparation of
      moderately curved canals. Single teeth with multiple canals can be prepared
      safely even by a novice operator by using a single file.

PMID- 24303358
TI  - A preliminary report on histological outcome of pulpotomy with endodontic
      biomaterials vs calcium hydroxide.
AB  - OBJECTIVES: The purpose of the study was to evaluate human dental pulp response
      to pulpotomy with calcium hydroxide (CH), mineral trioxide aggregate (MTA), and
      calcium enriched mixture (CEM) cement. MATERIALS AND METHODS: A total of nine
      erupted third molars were randomly assigned to each pulpotomy group. The same
      clinician performed full pulpotomies and coronal restorations. The patients were
      followed clinically for six months; the teeth were then extracted and prepared
      for histological assessments. The samples were blindly assessed by an independent
      observer for pulp vitality, pulp inflammation, and calcified bridge formation.
      RESULTS: All patients were free of clinical signs/symptoms of
      pulpal/periradicular diseases during the follow up period. In CH group, one tooth
      had necrotic radicular pulp; other two teeth in this group had vital uninflamed
      pulps with complete dentinal bridge formation. In CEM cement and MTA groups all
      teeth had vital uninflamed radicular pulps. A complete dentinal bridge was formed
      beneath CEM cement and MTA in all roots. Odontoblast-like cells were present
      beneath CEM cement and MTA in all samples. CONCLUSIONS: This study revealed that
      CEM cement and MTA were reliable endodontic biomaterials in full pulpotomy
      treatment. In contrast, the human dental pulp response to CH might be
      unpredictable.

PMID- 24303359
TI  - Effects of dentin moisture on the push-out bond strength of a fiber post luted
      with different self-adhesive resin cements.
AB  - OBJECTIVES: This study evaluated the effects of intraradicular moisture on the
      pushout bond strength of a fibre post luted with several self-adhesive resin
      cements. MATERIALS AND METHODS: ENDODONTICALLY TREATED ROOT CANALS WERE TREATED
      WITH ONE OF THREE LUTING CEMENTS: (1) RelyX U100, (2) Clearfil SA, and (3) G-Cem.
      Roots were then divided into four subgroups according to the moisture condition
      tested: (I) dry: excess water removed with paper points followed by dehydration
      with 95% ethanol, (II) normal moisture: canals blot-dried with paper points until
      appearing dry, (III) moist: canals dried by low vacuum using a Luer adapter, and
      (IV) wet: canals remained totally flooded. Two 1-mm-thick slices were obtained
      from each root sample and bond strength was measured using a push-out test setup.
      The data were analysed using a two-way analysis of variance and the Bonferroni
      post hoc test with p = 0.05. RESULTS: Statistical analysis demonstrated that
      moisture levels had a significant effect on the bond strength of luting cements
      (p < 0.05), with the exception of G-Cem. RelyX U100 displayed the highest bond
      strength under moist conditions (III). Clearfil SA had the highest bond strength
      under normal moisture conditions (II). Statistical ranking of bond strength
      values was as follows: RelyX U100 > Clearfil SA > G-Cem. CONCLUSIONS: The degree
      of residual moisture significantly affected the adhesion of luting cements to
      radicular dentine.

PMID- 24303360
TI  - Effect of Epigallocatechin Gallate on shear bond strength of composite resin to
      bleached enamel: an in vitro study.
AB  - OBJECTIVES: The aim of this study was to determine the effect of epigallocatechin
      gallate (EGCG) on the shear bond strength of composite resin to bleached enamel.
      MATERIALS AND METHODS: Ninety enamel surfaces of maxillary incisors were randomly
      divided into 9 groups as follows: G1: control (no bleaching); G2: bleaching; G3:
      bleaching and storage for seven days; G4 - 6: bleaching and application of 600,
      800 and 1,000 umol of EGCG-containing solution for 10 minutes, respectively; G7 -
      9: bleaching and application of 600, 800 and 1,000 umol of EGCG-containing
      solution for 20 minutes, respectively. The specimens were bleached with 30%
      hydrogen peroxide gel and a composite resin cylinder was bonded on each specimen
      using a bonding agent. Shear bond strength of the samples were measured in MPa.
      Data was analyzed using the two-way ANOVA and Tukey HSD tests (alpha = 0.05).
      RESULTS: The maximum and minimum mean shear bond strength values were observed in
      G1 and G2, respectively. Time and concentration of EGCG showed no significant
      effects on bond strength of the groups (p > 0.05). Multiple comparison of groups
      did not reveal any significant differences between the groups except for G2 and
      all the other groups (p < 0.05). CONCLUSIONS: There is a significant decrease in
      bond strength of composite resin to enamel immediately after bleaching. A delay
      of one week before bonding and the use of EGCG increased bond strength of
      composite resin to bleached enamel.

PMID- 24303361
TI  - Washout resistance of fast-setting pozzolan cement under various root canal
      irrigants.
AB  - OBJECTIVES: Fast-setting pozzolan cement (Endocem, Maruchi) was recently
      developed. The aim of this study was to investigate the effects of various root
      canal irrigants on the washout of Endocem in comparison to the previously
      marketed mineral trioxide aggregate (ProRoot; Dentsply) in a furcal perforation
      model. MATERIALS AND METHODS: ProRoot and Endocem were placed into acrylic molds
      on moist Oasis. Each mold was then immediately exposed to either physiologic
      saline, 2.5% sodium hypochlorite (NaOCl), or 2% chlorhexidine (CHX) under gentle
      shaking for five minutes. Washout testing was performed by scoring scanning
      electron microscope (SEM) images. RESULTS: Endocem exhibited higher washout
      resistance compared to ProRoot, especially in the NaOCl group. CONCLUSIONS: These
      results suggest that Endocem can be considered a useful repair material for
      furcal perforation, especially in a single-visit scenario.

PMID- 24303362
TI  - Endodontic treatment of maxillary lateral incisors with anatomical variations.
AB  - Maxillary lateral incisors usually exhibit a single root with a single canal.
      However, maxillary lateral incisor teeth with unusual morphology of root canal
      system are frequently reported. These cases of variable root canal anatomy can be
      treated well by nonsurgical endodontic methods. A detailed description of root
      canal morphology is fundamental for successful endodontic treatment. Treatment
      using an operating microscope, radiographs from different angles, and cone-beam
      computerized tomography (CBCT) can produce more predictable endodontic outcomes. 

PMID- 24303364
TI  - Statistical notes for clinical researchers: Understanding standard deviations and
      standard errors.

PMID- 24303363
TI  - Conservative approach of a symptomatic carious immature permanent tooth using a
      tricalcium silicate cement (Biodentine): a case report.
AB  - The restorative management of deep carious lesions and the preservation of pulp
      vitality of immature teeth present real challenges for dental practitioners. New
      tricalcium silicate cements are of interest in the treatment of such cases. This
      case describes the immediate management and the follow-up of an extensive carious
      lesion on an immature second right mandibular premolar. Following anesthesia and
      rubber dam isolation, the carious lesion was removed and a partial pulpotomy was
      performed. After obtaining hemostasis, the exposed pulp was covered with a
      tricalcium silicate cement (Biodentine, Septodont) and a glass ionomer cement
      (Fuji IX extra, GC Corp.) restoration was placed over the tricalcium silicate
      cement. A review appointment was arranged after seven days, where the tooth was
      asymptomatic with the patient reporting no pain during the intervening period. At
      both 3 and 6 mon follow up, it was noted that the tooth was vital, with normal
      responses to thermal tests. Radiographic examination of the tooth indicated
      dentin-bridge formation in the pulp chamber and the continuous root formation.
      This case report demonstrates a fast tissue response both at the pulpal and root
      dentin level. The use of tricalcium silicate cement should be considered as a
      conservative intervention in the treatment of symptomatic immature teeth. 

PMID- 24303365
TI  - Light curing of dual cure resin cement.

PMID- 24303366
TI  - Current advances in mathematical modeling of anti-cancer drug penetration into
      tumor tissues.
AB  - Delivery of anti-cancer drugs to tumor tissues, including their interstitial
      transport and cellular uptake, is a complex process involving various
      biochemical, mechanical, and biophysical factors. Mathematical modeling provides
      a means through which to understand this complexity better, as well as to examine
      interactions between contributing components in a systematic way via
      computational simulations and quantitative analyses. In this review, we present
      the current state of mathematical modeling approaches that address phenomena
      related to drug delivery. We describe how various types of models were used to
      predict spatio-temporal distributions of drugs within the tumor tissue, to
      simulate different ways to overcome barriers to drug transport, or to optimize
      treatment schedules. Finally, we discuss how integration of mathematical modeling
      with experimental or clinical data can provide better tools to understand the
      drug delivery process, in particular to examine the specific tissue- or compound
      related factors that limit drug penetration through tumors. Such tools will be
      important in designing new chemotherapy targets and optimal treatment strategies,
      as well as in developing non-invasive diagnosis to monitor treatment response and
      detect tumor recurrence. 

PMID- 24303368
TI  - Yeast programed cell death and aging.

PMID- 24303369
TI  - Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical
      Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung
      Cancer.
AB  - PURPOSE: To assess clinical outcomes and toxicities in patients with stage III
      unresectable non-small cell lung cancer (NSCLC) treated with a moderately
      escalated hypofractionated radiotherapy delivered with Helical Intensity
      Modulated Technique in combination with sequential or concurrent chemotherapy.
      MATERIALS AND METHODS: Sixty-one consecutive patients considered non-progressive
      after two cycles of induction chemotherapy were treated with a moderately
      escalated hypofractionated radiation course of 30 daily fractions of 2.25-2.28 Gy
      each administered in 6 weeks up to a total dose of 67.5-68.4 Gy (range, 64.5-71.3
      Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles)
      of chemotherapy, while 29 were treated with concurrent chemo-radiation. The
      target was considered the gross tumor volume and the clinically proven nodal
      regions, without elective nodal irradiation. RESULTS: With a median follow up of
      27 months (range 6-40), 1-year and 2-year OS rate for all patients was 77 and
      53%, respectively, with a median survival duration of 18.6 months in the
      sequential group and 24.1 months in the concomitant group. No Grade >=4 acute and
      late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was
      detected in 10% of patients. Two patients, both receiving the concurrent
      schedule, developed a Grade 3 acute esophagitis. The overall incidence of late
      Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal
      toxicity. CONCLUSION: A moderately hypofractionated radiation course delivered
      with a Helical Intensity-Modulated Technique is a feasible treatment option for
      patients with unresectable locally advanced NSCLC receiving chemotherapy
      (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated
      technique allows safely dose escalation, minimizing the effect of tumor
      repopulation that may occur with prolonged treatment time.

PMID- 24303370
TI  - Role of fine needle aspiration cytology in diagnosis of solitary thyroid nodules.
AB  - INTRODUCTION: This study was conducted at the Department of ear, nose, throat,
      head and neck surgery, Post Graduate Medical Institute Lady Reading Hospital
      Peshawar. The duration of the study was one year from June 17, 2009 to June 16,
      2010. The sample size was 82 patients with solitary thyroid nodule, fulfilling
      the inclusion criteria. After taking detailed history, thorough examination,
      relevant investigation and informed consent fine needle aspiration cytology was
      performed in all cases by the same cytopathologist. Thyroid surgery was performed
      and specimens were examined by the same histopathologist. The statistical
      analysis was performed using the statistical program for social sciences (SPSS
      version 11). MATERIALS AND METHODS: Our study included 82 cases consisting on 57
      female and 25 male, with female: male ratio of 2.28: 1.The age of the patients
      was ranged from 16-65 years with mean age of 42.56 + S.D 11.60 years. Most of the
      patients presented in 3(rd) and 4(th) decade followed by the 5(th) and 2(nd)
      decade. The diagnostic yield of Fine Needle Aspiration Cytology (FNAC) in this
      study was accuracy 82.92%, sensitivity 88.09%, specificity 77.50% and positive
      predictive value was 80.43%. RESULTS: One hundred twenty six patients entered the
      study among which 77 (61%) were female and 49 (39%) male. Mean age was obtained
      as 26.9 +/- 7.7 yrs. Up to 79.4% of patients had complaints concerning the
      cosmetic outcomes, 39.7% with respiratory and 4.8% with olfactory problems. The
      reason to sue the physician had a significant relationship with the patients' age
      and sex, and also with the surgeons' experience. CONCLUSION: FNAC has key rule in
      diagnosis of solitary thyroid nodule because it is safe, minimally invasive and
      cost effective diagnostic tool.

PMID- 24303371
TI  - Litigation after nasal plastic surgery.
AB  - INTRODUCTION: Esthetic surgeries are among the commonest medical procedures in
      the world nowadays; and as statistics declare, there has been a rapid increase in
      the rate of rhinoplasty during the recent years. Hence, as the number of cosmetic
      surgeries rises, the increment in the number of physicians being sued is quite
      inevitable; either due to complication in rhinoplasties or even inability to
      fulfill the patients' expectations. This article aims to clarify the aspects of
      causes leading to these legal claims. MATERIALS AND METHODS: We designed a
      retrospective study according to the available files in the Iranian Organization
      for Forensic Medicine in which physicians were sued for the outcomes of
      rhinoplasty through the years 2004 to 2010. In addition, information on the
      patients' demographic data, surgeons' specialty and experience, and method of
      anesthesia were also collected. RESULTS: One hundred twenty six patients entered
      the study among which 77 (61%) were female and 49 (39%) male. Mean age was
      obtained as 26.9 +/- 7.7yrs. Up to 79.4% of patients had complaints concerning
      the cosmetic outcomes, 39.7% with respiratory and 4.8% with olfactory problems.
      The reason to sue the physician had a significant relationship with the patients'
      age and sex, and also with the surgeons' experience. CONCLUSION: There are
      multiple reasons impelling the patients to sue surgeons after rhinoplasty, some
      are related to physicians' malpractice and some to the patients' social and
      personal circumstances.

PMID- 24303372
TI  - Evaluation of hearing results in otosclerotic patients after stapedectomy.
AB  - INTRODUCTION: Otosclerosis one of the most common causes of conductive hearing
      loss is more common in females and in their middle ages. It is usually a
      bilateral and progressive disease. Surgical operation is suggested as the
      exclusive management of otosclerosis. This study aims to evaluate the hearing
      results after stapedectomy in otosclerotic patients in Ahwaz. MATERIALS AND
      METHODS: In this case series study, the records of otosclerotic patients who had
      undergone stapedectomy or stapedotomy in Imam Khomeini and Apadana Hospitals of
      Ahwaz, Iran during 1997-2007 were evaluated. All the operations were performed by
      a single surgeon (first author). Data were analyzed using SPSS and descriptive
      statistical tests. RESULTS: One hundred ninety seven patients were included in
      this study. 66.8% were female and the age range was 20-40 years. The affected
      ears were reported as follows: right ear (65%), left ear (35%) and bilateral
      (18%). ABG was reported as less than 10db in 63.9% of patients; between 10 to
      20db in 29.99% and more than 20db in 5%. Surgical complications were observed in
      4.5% of patients (1.5% intraoperatively and 3% postoperatively). DISCUSSION:
      Saccular dysfunction seems to be an important finding in SSNHL. Although it is
      more prevalent in the patients with vertigo, it can be found in the non-dizzy
      cases. VEMP disturbance in SSNHL shows more extensive pathological involvement.
      CONCLUSION: Just like previously conducted studies, satisfactory surgical
      outcomes with rare complications were observed in the appropriate population
      under study.

PMID- 24303367
TI  - Risk factors and therapeutic targets in pancreatic cancer.
AB  - Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide,
      characterized as a highly aggressive disease with dismal overall prognosis and an
      incidence rate equalling mortality rate. Over the last decade, substantial
      progress has been made to define the morphological changes and key genetic events
      in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger
      PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or
      other rare genetic conditions. Additionally, modifying factors such as smoking,
      obesity, diabetes, occupational risk factors, etc., increase the potential for
      acquiring genetic mutations that may result in PC. Another hallmark of PC is its
      poor response to radio- and chemo-therapy. Current chemotherapeutic regimens
      could not provide substantial survival benefit with a clear increase in overall
      survival. Recently, several new approaches to significantly improve the clinical
      outcome of PC have been described involving downstream signaling cascades
      desmoplasia and stromal response as well as tumor microenvironment, immune
      response, vasculature, and angiogenesis. This review summarizes major risk
      factors for PC and tries to illuminate relevant targets considerable for new
      therapeutic approaches. 

PMID- 24303373
TI  - Sinonasal headaches and post-operative outcomes after septoplasty in patients
      with nasal septal deviation.
AB  - INTRODUCTION: Investigators believe that anatomical abnormalities in the
      sinonasal region can be the cause of some chronic and refractory headaches that
      may respond well to surgical intervention. This study presents the prevalence of
      headache in patients with nasal septal deviation and their response to surgical
      treatment over a 2-year follow-up period. MATERIALS AND METHODS: This descriptive
      and prospective study was conducted on 98 patients with nasal septal deviation
      who underwent septoplasty surgery in the Imam Hospital in Ahwaz. Preoperative
      information was acquired by asking the patients and by completing SNOT-20
      questionnaires by patients. After the surgery, information about changes in the
      quality of headache in patients with dominant contact points in preoperative
      nasal endoscopy whose headache responded to topical anaesthesia with lidocaine
      2%+naphazoline 0.5% was collected over a 2-year follow-up. Final data were
      analyzed by SPSS and descriptive statistics. RESULTS: Ninety-eight patients were
      studied, comprising 58.2% men and 41.8% women. They ranged in age between 18 and
      46 years (mean=24). Nasal obstruction (72.4%), snoring (58.1%), headache (46%)
      and epistaxis (17.3%) were the most frequent preoperative symptoms. The most
      common site of the headache was the frontal region (68.8%). Patients' headache
      was bilateral in 71.1% of cases. In 82.2% of patients, headache lasted less than
      four hours a day. The headache was pulsatile in 53.3%, sharp in 31.2% and
      compressive in 15.5% of cases. In the post-operative assessment, despite gradual
      decline in the referral patients for follow-up, a notable and gradual recovery in
      patients' headache was seen with 82.8% of the patients reporting complete or
      partial recovery of the headache at the end of the 2-year follow-up. CONCLUSION:
      Headache is one of the most common symptoms in patients with nasal anatomical
      abnormalities such as septal deviation and usually responds well to surgical
      treatment. More studies with long-term follow-ups seems to be inevitable to
      determine the relationship between headaches and nasal anatomical abnormalities,
      accurate surgical results in patients' recovery and the recurrence rate of
      headaches.

PMID- 24303374
TI  - Noise pollution in intensive care units and emergency wards.
AB  - INTRODUCTION: The improvement of technology has increased noise levels in
      hospital Wards to higher than international standard levels (35-45 dB). Higher
      noise levels than the maximum level result in patient's instability and
      dissatisfaction. Moreover, it will have serious negative effects on the staff's
      health and the quality of their services. The purpose of this survey is to
      analyze the level of noise in intensive care units and emergency wards of the
      Imam Reza Teaching Hospital, Mashhad. PROCEDURE: This research was carried out in
      November 2009 during morning shifts between 7:30 to 12:00. Noise levels were
      measured 10 times at 30-minute intervals in the nursing stations of 10 wards of
      the emergency, the intensive care units, and the Nephrology and Kidney Transplant
      Departments of Imam Reza University Hospital, Mashhad. The noise level in the
      nursing stations was tested for both the maximum level (Lmax) and the equalizing
      level (Leq). The research was based on the comparison of equalizing levels (Leq)
      because maximum levels were unstable. RESULTS: In our survey the average level
      (Leq) in all wards was much higher than the standard level. The maximum level
      (Lmax) in most wards was 85-86 dB and just in one measurement in the Internal ICU
      reached 94 dB. The average level of Leq in all wards was 60.2 dB. In emergency
      units, it was 62.2 dB, but it was not time related. The highest average level
      (Leq) was measured at 11:30 AM and the peak was measured in the Nephrology
      nursing station. CONCLUSION: The average levels of noise in intensive care units
      and also emergency wards were more than the standard levels and as it is known
      these wards have vital roles in treatment procedures, so more attention is needed
      in this area.

PMID- 24303375
TI  - Pseudoexfoliation syndrome and sensorineural hearing loss.
AB  - INTRODUCTION: Pseudoexfoliation syndrome (PXS) occurs due to the deposition of
      extracellular fibrillar materials on the anterior chamber of the eye. This
      syndrome has been considered to be part of a systemic disease with the potential
      involvement of the inner ear called sensoroneural hearing loss (SNHL). In this
      study, we aimed on evaluating SNHL within PXS patients in Iran to compare them
      with other international reports. MATERIALS AND METHODS: In total, 33 patients
      with PXS and 33 age and sex matched controls were enrolled prospectively in a
      case-control study. Both groups underwent complete ophthalmologic and
      otorhinolaryngologic examinations and pure tone audiometry (PTA) testing. Six
      frequencies (0.25, 0.5, 1, 2, 3, 4 and 6 KHz) were evaluated for PTA in the same
      ethnic group in order to select the case and control individuals. Data were
      analyzed using t-test and chi-square test. RESULTS: Forty-nine out of 66 ears
      (75.2%) in the PXS group and 27 ears (40.9%) in the control group had SNHL
      (P<0.001). No significant difference was found between the existence of
      exfoliative glaucoma (EXG) and SNHL in the PXS patients (P=0.768). CONCLUSION:
      Our results indicate a significant association between PXS and SNHL and may
      support the systemic nature of this disease.

PMID- 24303376
TI  - Castleman's Disease, a Case report.
AB  - INTRODUCTION: Castleman's disease is a rare lymphoproliferative disorder which
      may be confused with other causes of lymphadenopathy. CASE REPORT: Here we report
      a case of unicentric Castleman's disease presenting with cervical
      lymphadenopathy. The patient was treated with complete surgical excision of
      lesion and was disease free at the time of reporting this article. This case has
      been reported for its rarity. CONCLUSION: Though castleman's disease is a
      relatively rare entity it should be strongly considered in the differential
      diagnosis of cervical lymphadenopathy.

PMID- 24303377
TI  - Recurrence of cholesteatoma mimicking dural herniation.

PMID- 24303378
TI  - Effects of parents' level of education and economic status on the age at cochlear
      implantation in children.
AB  - INTRODUCTION: Cochlear implantation can facilitate the development of
      communication skills in children with profound hearing loss. The objectives of
      our study were to determine the average ages at suspicion and diagnosis of
      hearing loss, amplification, intervention, and performing the cochlear
      implantation and to investigate the effects of the parents' level of education
      and economic circumstances on the age of the child at cochlear implantation.
      MATERIALS AND METHODS: The parents of 96 children with profound sensorineural
      hearing loss who had received a cochlear implant at Amir-Alam Cochlear Implant
      Center between 2008 and 2010 were asked to complete a survey. The survey included
      demographic information, and birth, medical, and hearing loss history of their
      child. Study data were obtained through the patient database in the Cochlear
      Implant Center and interviews with the parents. RESULTS: The mean times between
      the age of the children at diagnosis of hearing loss and amplification, beginning
      the rehabilitation program, and performing the cochlear implantation were 4.05
      (+/-0.86), 2.59 (+/-0.9), and 25.43 (+/-1.45) months, respectively; delays that
      were statistically significant (P<=0.004). In 47.9 percent of cases, the parents
      were the first people to suspect the occurrence of hearing loss in their child.
      Statistical analysis indicated that the age at cochlear implantation decreases as
      the educational level of the parents increases (P<=0.003). There was also a
      significant difference between parents' economic circumstances and the age of
      cochlear implantation (P<0.0001). CONCLUSION: There is still a remarkable delay
      between the diagnosis of hearing loss and aural rehabilitation in hearing
      impaired children. Parents' levels of education and economic circumstances have a
      noticeable effect on the age of cochlear implantation in hearing-impaired
      children.

PMID- 24303379
TI  - Incidence of Complications Developed after the Insertion of Ventilation Tube in
      Children under 6 years old in 2008-2009.
AB  - INTRODUCTION: One of the main treatments of chronic otitis media with effusion is
      ventilation of the middle ear with a ventilation tube (VT). The objective of this
      study was to determine the incidence and the types of VT complications in
      children with otitis media with effusion in Ahwaz. MATERIALS AND METHODS: In this
      prospective study, the medical records of 208 children (52 male and 35 female) in
      Imam Khomeini and Apadana hospitals were reviewed. The children were between 10
      months and 6 years old. The patients were followed up 12-18 months after
      ventilation tube insertion. We reviewed age, sex, postoperative otorrhea, eardrum
      atrophy, tympanosclerosis and persistent perforation. In all these patients, the
      indication for surgery was chronic middle ear effusion. The data were analyzed
      and presented as numbers and percentages using SPSS17.0. RESULTS: Transient
      otorrhea occurred in 12.5% and delayed otorrhea in 8.2%. Otorrhea non-responsive
      to medical treatment was seen in 1.9%. Complications after tympanostomy tube
      extrusion included atrophy (27.8%) myringosclerosis (37.9%), and persistent
      perforation (2.4%).The average extrusion time was 10.5 +/-5 months (ranging
      between 3-22 months). CONCLUSION: After extrusion of the ventilation tube,
      patients should be followed up regularly for recurrence of OME. Myringosclerosis,
      tympanic membrane atrophy and otorrhea are the most common complications of
      otitis media with effusion. However, they are generally insignificant.
      Consequently, in the majority of these complications, there is no need for any
      treatment.

PMID- 24303380
TI  - The effect of intratympanic dexamethasone with oral prednisolone as a primary
      treatment in idiopathic sudden sensorineural hearing loss.
AB  - INTRODUCTION: Sudden sensorineural hearing loss (SSNHL) is a true emergency that
      must be diagnosed and treated immediately. The purpose of this study is to
      compare the efficacy of treatment with intratympanic dexamethasone plus oral
      prednisolone daily or every other day with that of treatment with oral
      prednisolone alone. MATERIALS AND METHODS: Sixty-three patients with SSNHL that
      had been present for less than 10 days prior to the start of treatment were
      randomly allocated to three different groups. Patients in group A were treated
      daily with oral prednisolone 1 mg/kg for 10 days plus intratympanic dexamethasone
      2 mg for the first 3 days of treatment. Patients in group B were treated every
      other day with oral prednisolone 1 mg/kg for 10 days with the addition of
      intratympanic dexamethasone 2 mg for the first 3 treatments. Patients in group C
      were treated daily with oral prednisolone 1 mg/kg alone for 10 days. Audiometric
      parameters including pure tone audiometry (PTA), speech reception threshold
      (SRT), and speech discrimination score (SDS) were assessed on days 1,5, and 10.
      RESULTS: There was a significant improvement in PTA, SRT and SDS in each group
      over the 10 days but the greatest improvement was seen in the SRT measurements of
      group A in comparison with group B (19.81 +/- 2.15, P=0.04) and C (26.26 +/-
      0.08, P=0.01). The difference in SRT between groups B and C was not statistically
      significant. CONCLUSION: The administration of intratympanic dexamethasone 2 mg
      daily for 3 days has an additive effect to that of 10 days of oral prednisolone 1
      mg/kg in the treatment of SSNHL.

PMID- 24303381
TI  - The effect of ketamine on posttonsillectomy pain in children: a clinical trial.
AB  - INTRODUCTION: Tonsillectomy is one of the most common surgical operations and has
      such complications as pain, hemorrhage and laryngospasm. Pain management is of
      vital importance in order to reduce the suffering and restlessness in children
      having undergone tonsillectomy. Different studies differ in their findings as to
      the use of ketamine for postoperative analgesia. The aim of this study was to
      investigate the effect of peritonsillar injection of ketamine preoperatively on
      postoperative pain relief. MATERIALS AND METHODS: This was a randomized
      controlled trial (RCT) on sixty 3-12-year-old children. Children were randomly
      assigned to the intervention and control groups. Peritonsillar injection
      consisted of 1 mg/kg ketamine in the intervention group and of normal saline in
      the control group. An injection of 1 cc was administered on each side five
      minutes prior to tonsillectomy. Pain assessment was performed using the self
      report Oucher Scale and CHEOPS (Children's Hospital of Eastern Ontario Pain
      Scale) and sedative state assessment was performed using the Wilson Sedation
      Scale. Pain, medication and complications were studied for 24 hours. Data
      analysis was performed using chi-squared test and t-test. RESULTS: The ketamine
      group had a lower pain score compared with the control group (1.40+/-1.003
      compared with 1.53+/-1.074). The average pain was less in the control group two
      hours after the surgery. The difference was statistically significant. There was
      no difference between the two groups in terms of nausea and vomiting incidence.
      CONCLUSION: The peritonsillar injection of ketamine five minutes prior to the
      surgery reduces the post-tonsillectomy pain without causing any complications.

PMID- 24303382
TI  - The prevalence of positive fungal cultures in patients with chronic
      rhinosinusitis in a high altitude region of iran.
AB  - INTRODUCTION: There are suspended fungal spores in the air and in the nasal
      mucosa of adults, especially in areas with a humid climate. Several studies have
      revealed the role of fungi in the pathogenesis of chronic rhinosinusitis (CRS) in
      recent years but it is a topic of controversy, especially in regions with low
      humidity. The aim of this study was to evaluate the prevalence of fungal species
      in intraoperative specimens from patients who underwent functional endoscopic
      sinus surgery (FESS) for CRS in Hamadan, a high altitude region of Iran.
      MATERIALS AND METHODS: In this prospective cross-sectional study specimens were
      obtained from 62 patients with a diagnosis of CRS according to clinical and
      computed tomography criteria who underwent endoscopic sinus surgery. During the
      functional endoscopic sinus surgery, specimens were collected from the nose and
      sinuses of patients and preserved in conical centrifuge tubes containing
      Sputolysin and chloramphenicol. The specimens were then plated on Sabouraud
      dextrose agar, Mycosel agar, Niger seed agar, and Chrom Agar/Candida plates and
      incubated at 30 degrees C for up to 1 month. At the end of the incubation period
      the samples were evaluated microscopically to detect fungi and identify their
      genera and species. RESULTS: The fungal cultures were positive in 16 out of 62
      patients with CRS (25.8%). In order of frequency the fungal genera and species
      were: Aspergillus fumigatus (9), Aspergillus niger (3), Candida albicans (2),
      Penicillium sp. (1) and Cladosporium sp. (1). The percentage of positive cultures
      collected was higher in winter but the difference was not statistically
      significant compared to the rest of the year. CONCLUSION: Our data show that
      25.8% of patients tested positive for the presence of fungi. The results
      strengthen the theory regarding the role of fungi in the pathogenesis of CRS even
      in areas with low humidity. Aspergillus was the most commonly isolated fungus.

PMID- 24303383
TI  - Audiological manifestations in vitiligo patients.
AB  - INTRODUCTION: The hallmark of vitiligo is the disappearance of melanocytes from
      the skin due to an as yet unidentified mechanism. The presence of melanocytes in
      the auditory apparatus suggests that this system could possibly be affected by
      vitiligo, which targets the melanocytes of the whole body and not just the skin.
      The purpose of this study was to assess the incidence of auditory alterations in
      patients with vitiligo. MATERIALS AND METHODS: A total of 21 patients diagnosed
      with vitiligo were enrolled in this study. A group of 20 healthy subjects served
      as a control group. Pure tone audiometry (PTA) and measurements of auditory brain
      stem responses (ABR) were carried out in all participants. RESULTS: High
      frequency sensory neural hearing loss was detected in 8 patients (38.09%).
      Analysis of ABR revealed that 10 patients (47.61%) had an abnormal increase in
      the latency of Wave III and 6 (28.57%) had an abnormal prolongation of the inter
      peak latency between Wave I and III. There was no correlation between age,
      duration of disease, and any of the recorded parameters. CONCLUSION: This study
      highlights the involvement of the auditory system in patients with vitiligo,
      suggesting that vitiligo is a systemic disease rather than a purely cutaneous
      problem.

PMID- 24303384
TI  - Lobular capillary hemangioma of middle turbinate literature survey and case
      report.
AB  - INTRODUCTION: Lobular capillary hemangioma (LCH) is a benign lesion of vascular
      origin. It rarely involves nasal cavity which most commonly manifests as
      progressive nasal obstruction and epistaxis. CASE REPORT: In this report we
      present a case of LCH of the nasal cavity which occurred approximately one month
      after delivery. There was no recurrence after complete endoscopic resection
      during one year follow up.

PMID- 24303385
TI  - A case report: nager acrofacial dysostosis.
AB  - INTRODUCTION: Nager syndrome is a malformation resulting from problems in the
      development of the first and second branchial arches and limb buds. The cause of
      the abnormal development of the pharyngeal arches in Nager syndrome is unknown.
      It is also unclear why affected individuals have bone abnormalities in their arms
      and legs. Nager syndrome is thought to have an autosomal recessive inheritance
      pattern when unaffected parents have more than one affected child. The purpose of
      this report is to present a case of Nager syndrome where the patient exhibited
      upper limb shortening, an unusual feature that has been reported as coexisting in
      some individuals with Nager syndrome. CASE REPORT: A 3.5-year-old girl was
      referred to our Department of Pediatric Otorhinolaryngology due to a cleft
      palate. Her craniofacial anomalies included malar hypoplasia, severe mandibular
      hypoplasia with retrognathia, downward slanted palpebral fissures, a high narrow
      hard palate, absent soft palate, small retroplaced tongue, bilateral external
      auditory canal atresia, and dysplastic ears. There was no evidence of mental
      retardation. Based on the craniofacial characteristics and the coexisting upper
      limb preaxial anomalies, a diagnosis of Nager syndrome was confirmed. CONCLUSION:
      Nager syndrome is a rare disorder resulting from developmental abnormalities of
      the first and second branchial arches. It is linked to five other similar
      syndromes: Miller syndrome, Treacher-Collins, Pierre-Robin, Genee-Wiedemann, and
      Franceschetti-Zwahlen-Klein. Multidisciplinary management by a craniofacial team
      is needed. Early intervention, intensive education, new surgical techniques, and
      an emphasis on coordinated care have improved the quality of life in this patient
      with Nager syndrome.

PMID- 24303386
TI  - Have guidelines affected ear, nose, and throat specialists' diagnoses and the
      prescription of antibiotics for acute otitis media?
AB  - INTRODUCTION: The Ministry of Health and Medical Education of Iran, and similar
      institutions in many other countries, advises physicians to use current
      guidelines for the diagnosis and treatment of acute otitis media (AOM). However,
      there has been no evaluation of the effectiveness of such guidelines or whether
      physicians in Iran adhere to them. Thus, as laryngologists are the most important
      group of people who interact with patients with AOM, the aim of this study was to
      evaluate the attitude of laryngologists to the established guidelines. MATERIALS
      AND METHODS: A total of 120 anonymous surveys were mailed to 120
      otolaryngologists in Tehran, Iran, to evaluate the patterns of diagnosis and
      treatment of AOM used by these physicians. The survey included questions
      regarding the otolaryngologists' age, gender, place of work, and attitude towards
      diagnosis and treatment of AOM. RESULTS: Sixty-two completed surveys were
      received, for a response rate of 51%. There was no significant difference between
      respondents to these surveys according to sex, age, practice setting, graduation
      year, or the number of patients with AOM seen each month. CONCLUSION: Our study
      adds new insights to the previous literature on the use of guidelines in the
      management of AOM. We can now assess the impact of guidelines on the usual
      practice of physicians in evidenced-based management of AOM.

PMID- 24303387
TI  - A comparative study of two different uncinectomy techniques: swing-door and
      classical.
AB  - INTRODUCTION: The aim of this study was to determine which technique of
      uncinectomy, classical or swing door technique. MATERIALS AND METHODS: Four
      hundred eighty Cases of sinusitis were selected and operated for Functional
      Endoscopic Sinus Surgery (FESS). Out of these, in 240 uncinectomies classical
      uncinectomy was done whereas in another 240 uncinectomies swing door technique
      was used. Initially patients were medically managed treated according to their
      symptoms and prior management. Patients who had received previous adequate
      medical management were evaluated with CT scan of the sinuses. If disease still
      persists than they were operated for FESS. RESULTS: The authors' experience
      indicates that Functional endoscopic sinus surgery can be performed under local
      or general anesthesia, as permitted or tolerated. In this review classical
      technique was used in 240 uncinectomies. Out of this, ethmoidal complex injury
      was noted in 4 cases, missed maxillary ostium syndrome (incomplete removal) was
      reported in 12 patients and orbital fat exposure was encountered in 5 patients.
      As compared to 240 uncinectomies done with swing door technique, incomplete
      removal was evident in 2 cases and lacrimal duct injury was reported in 3 cases.
      'Evidence that underscores how this 'swing door technique' successfully combines
      'the conservation goals of the anterior-to-posterior approach and anatomic
      virtues of the posterior-to-anterior approach to ethmoidectomy of the total 480
      uncinectomies operated. Out of which 240 uncinectomies have been performed using
      the 'swing-door' technique. The 240 uncinectomies performed using classical
      technique were used as controls. The incidence of orbital penetration, incomplete
      removal, ethmoidal complex injury and ostium non-identification was significantly
      less with the new technique. Three lacrimal injuries occurred with the 'swing
      door' technique compared to no injuries with classical technique. CONCLUSION: The
      authors recommend swing door technique as it is easy to learn, allows complete
      removal of the uncinate flush with the lateral nasal wall and allows easy
      identification of the natural ostium of the maxillary sinus without injuring the
      ethmoidal complex.

PMID- 24303388
TI  - Evaluation of children with chronic rhinosinusitis after adenotonsillectomy.
AB  - INTRODUCTION: Chronic rhinosinusitis (CRS), defined as an inflammatory process
      involving the paranasal sinuses that continues for at least three months, is a
      major cause of morbidity in the pediatric population and a difficult entity to
      treat with a poorly defined pathophysiology. The cornerstone of treatment for
      children with CRS remains aggressive antibiotic therapy, but many patients fail
      to improve even after extended courses of broad-spectrum oral antibiotics.
      However, good treatment results with adenoidectomy alone have been reported in
      pediatric patients with CRS. The purpose of this study was to evaluate the effect
      of adenotonsillectomy on chronic rhinosinusitis in children. MATERIALS AND
      METHODS: In this clinical trial the study population was 40 children under 14
      years old who had been selected for adenotonsillectomy. Prior to the procedure, a
      Waters' view radiograph was performed on individuals that suffered from CRS and
      displayed symptoms such as rhinorrhea, halitosis, and chronic cough. Only
      patients with bilateral clouding of the maxillary sinuses were enrolled in study.
      A further radiograph was performed on the 28(th) day following the procedure and
      the outcome of the treatment evaluated. RESULTS: Of the 40 patients under 14
      years old who were evaluated, 22 (55%) were female and 18 (45%) were male. The
      mean age of the patients was 7.22 years while the oldest was 14 and the youngest
      was 4 years old. Nasal congestion, rhinorrhea, post nasal drip, and chronic cough
      were present in all of the patients. Following the adenotonsillectomy, these
      symptoms were significantly reduced and were present in only 15.5%, 0%, 20%, and
      20% of the patients, respectively. Multivariate analyses were performed using
      McNemar's test. CONCLUSION: According to the results of this study, where 72.5%
      of patients showed a complete recovery following treatment, an adenotonsillectomy
      can be considered as a treatment modality for CRS.

PMID- 24303389
TI  - The Epidemiological and Clinical Aspects of Nasal Polyps that Require Surgery.
AB  - INTRODUCTION: The objective of this retrospective cross-sectional study was to
      obtain epidemiological data from the charts of 297 patients with nasal polyposis
      who were operated on in a referral hospital in Mashhad and to determine the
      frequency of the presenting symptoms of nasal polyps. MATERIALS AND METHODS: The
      variables recorded included age, gender, the presence of asthma or allergic
      rhinitis, family history, and previous treatments. We studied the main symptoms
      of nasal polyposis (nasal obstruction, rhinorrhea, anosmia, headache, epistaxis,
      snoring, and so on), as well as ear problems and facial deformity. RESULTS: Nasal
      polyposis affects men (60.3%) more frequently, at a mean age of 39.5 years. The
      most frequent symptom was nasal blockage (81.1 %) followed by rhinorrhea (37.7%).
      A total of 11.1% of the patients had a history of epistaxis. Asthma was found in
      10.4% of patients with nasal polyposis and the ears were affected in 5.1% of
      patients. In all, 7.4% of patients had first-degree relatives who suffered from
      asthma or allergic rhinitis. CONCLUSION: This study highlights the need for large
      scale epidemiologic research exploring the prevalence and incidence of nasal
      polyposis in Iran.

PMID- 24303390
TI  - Prophylactic antibiotics in otolaryngologic surgeries: from knowledge to
      practice.
AB  - INTRODUCTION: The management and use of antimicrobial drugs has clinical,
      economic, and environmental implications. In many countries, antimicrobial drugs
      are the most frequently prescribed therapeutic agents. Therefore, health-care
      policy should focus on how to establish a rational attitude toward antibiotics.
      This study was performed to investigate antibiotic usage as a prophylactic
      regimen in head and neck surgeries. MATERIALS AND METHODS: This study was a
      retrospective case series. Patients undergoing otolaryngology surgeries in a
      tertiary referral otolaryngology center were included. Members of operating room
      staff that were unaware of the study objectives collected patients' data using a
      questionnaire that contained information regarding general medical condition,
      disease, surgical procedure, and prophylaxis regimen and duration. RESULTS:
      Excluding infected patients, we studied 1349 patients during a four-month period
      who needed prophylactic antibiotics. A total of 34 different types of surgical
      procedures were performed. Out of the total number of patients, 503 (37.0%)
      received a parenteral antibiotic directly before surgery. The main antibiotics
      used before surgery were cephalosporins (94.9%). All of the 1349 patients were
      administered antibiotics after the procedure. These antibiotics where given with
      a mean number of doses of 4.81 (range: 1-68), and also consisted of mostly
      cephalosporins. CONCLUSION: Our results indicate that prophylactic antibiotics
      were being significantly misused in a tertiary referral center of a university
      hospital. Although teaching the principles of prophylaxis to physicians is
      important, we think that finding a way to bring this knowledge to practice is
      more important.

PMID- 24303391
TI  - Incidence of etiologic factors in squamous cell carcinoma of head and neck in
      ahvaz.
AB  - INTRODUCTION: Squamous cell carcinoma (SCC) is the most common head and neck
      malignancy. Smoking, alcohol consumption, viral infections, exposure, oral
      hygiene, and dietary, genetic, and occupational factors are the most important
      etiologic factors. The aim of this study was determining the incidence of
      etiologic factors in head and neck SCC. MATERIALS AND METHODS: This is a cross
      sectional survey study for the determination of the etiologic factors of head and
      neck squamous cell carcinoma over a five-year period in the Otolaryngology
      Department of the Imam Khomeini & Golestan hospitals in Ahwaz. RESULTS: 176
      patients, comprising 151(85.8%) men and 25(14.2%) women, were studied. Overall
      mean age was 67.2 years. 148 (84.1%) patients were smokers. prolong exposure to
      chemical fertilizer in 101 (57.4%) patients, Sun exposure in 21 (11.9%) patients,
      Low socioeconomic status in 124 (70.5%) patients, poor oral hygiene in 128
      (72.7%) patients, high intake of hot tea drinking in 84 (47.7%) patients and
      malignancies in family in 12 (6.8%) patients were the most frequent risk factors.
      17 (9.6%) patients have had opioid addiction and HPV was positive in 7 (3.9%)
      patients by PCR. CONCLUSION: According to this study, tobacco smoking was the
      most important etiologic factor and had a strong effect on risk of head and neck
      squamous cell carcinoma. Other factors are also important and need more research
      study.

PMID- 24303392
TI  - Foreign bodies: aspirated or ingested? A report of two unusual cases.
AB  - INTRODUCTION: The diagnosis of foreign bodies in the upper aerodigestive tract is
      usually straightforward but sometimes it can be delayed or the location of
      esophageal and upper airway foreign bodies can be mistakenly interchanged. CASE
      REPORT: We present two interesting cases that caused diagnostic challenges which
      could have led to serious complications if a greater delay in diagnosis had
      occurred. CONCLUSION: In order to diagnose upper aerodigestive tract foreign
      bodies without delay, a careful history and physical examination with proper X
      rays are helpful.

PMID- 24303393
TI  - A schwannoma of the soft palate in a child: histological and immunohistochemical
      features and surgical method.
AB  - INTRODUCTION: Schwannoma, or neurilemmoma, is a benign neoplasm of Schwann cells
      that is extremely rare in the soft palate. Herein we present a case of a soft
      palate schwannoma presenting with an ulcerated surface and purplish colour in a
      12 year-old girl. This report also introduces a successful surgical technique for
      coverage of the defect left by surgery.

PMID- 24303394
TI  - A Short-term Comparison Between Result of Palisade Cartilage Tympanoplasty and
      Temporalis Fascia Technique.
AB  - INTRODUCTION: The use of cartilage as a grafting material has been advocated in
      cases where there is a high risk of graft failure, such as subtotal perforations,
      adhesive processes, and residual defects after primary tympanoplasties. The
      purpose of this study was to compare the graft acceptance rates and auditory
      outcomes of cartilage tympanoplasty operations using a palisade technique with
      those of primary tympanoplasty using temporalis fascia in a homogenous group of
      patients. STUDY DESIGN: Prospective study. MATERIALS AND METHODS: The study
      population included 54 patients who were operated on in two groups (palisade
      technique & temporalis fascia technique) with each group containing 27 patients.
      Patients with pure subtotal perforations (perforation of >50% of the whole
      tympanic membrane [TM] area), an intact ossicular chain, at least a one month dry
      period, and normal middle ear mucosa were included in the study. Grafts
      acceptance rates and pre- and post-operative audiograms were compared. The follow
      up time was six months. RESULTS: Graft acceptance was achieved in all patients
      (100%) in the palisade cartilage tympanoplasty group and in 25 patients (92.5%)
      in the temporalis fascia group. This difference was not statistically significant
      (P= 0.15). Comparison of the increases in mean speech reception threshold, air
      bone gap, and pure-tone average scores between both techniques showed no
      significant changes. CONCLUSION: Our experience with the palisade cartilage
      technique demonstrates that subtotal or total perforation at high risk for graft
      failure can be treated efficiently, and that a durable and resistant
      reconstruction of the TM with reasonable auditory function can be achieved.

PMID- 24303395
TI  - Epidemiology of oral cavity cancers in a country located in the esophageal cancer
      belt: a case control study.
AB  - INTRODUCTION: As one of the most common cancers among head and neck malignancies,
      cancer of the oral cavity probably has some variations in countries with a high
      prevalence of esophageal cancer. MATERIALS AND METHODS: Patients with oral cavity
      cancer who were treated at two tertiary referral centers from January 1999 to
      January 2009 were included in this study. In addition to demographic data,
      information regarding personal and family history of head and neck cancer, use of
      dentures, presence of immune deficiency, consumption of alcohol, and incidence of
      cigarette smoking was collected. Additionally, a history of opium usage was
      obtained from the participants in this study. Moreover, an appropriately matched
      control group was selected for comparisons between the risk factors. RESULTS: A
      total of 557 patients were entered into this study over a 10-year period, of whom
      219 (39.3%) were female and the remaining 338 (60.7%) were male. The tongue was
      the most common site of cancer and 9% of the patients had a history of opium
      abuse, but more than half of the patients did not have any recognized risk
      factors. The incidence and stage of cancer had a significant relationship with
      cigarette smoking (P= 0.013). CONCLUSION: Tongue cancer in non-smokers is the
      predominant pattern of oral cavity cancer in Iran.

PMID- 24303396
TI  - Frequency of minor skin and soft tissue complications in facial and periorbital
      area after septorhinoplasty.
AB  - INTRODUCTION: High prevalence of rhinoplasty in the community and lack of
      structured studies about its minor skin and soft tissue complications, point out
      the necessity of performing precise and comprehensive studies. The aim of this
      study was to determine the frequency of minor cutaneous and soft tissue
      complications of rhinoplasty. MATERIALS AND METHODS: 110 patients (30 Male and 80
      Female, Mean age: 26.3+/- 6.8) participated in this study. Before surgery all of
      them were checked for having each of intended complications, and 1 and 3 months
      after the surgery, they underwent serial visits for monitoring skin & soft tissue
      complications. The software used for data analysis was SPSS ver.16. RESULTS: Acne
      exacerbation was seen in 27% of cases in first post-surgical visit. Nasal tip
      paresthesia was the most frequent complication in both postsurgical visits (49.6%
      in first and 36.3% in second visit), followed by eyebrow loss (31.8%), complaint
      of increased yawning (31.8%), periorbital hyperpigmentation (21.8%) in first
      visit, and, hyperpigmentation (19.1%), complaint of increased yawning (10%) and
      surgical site scar (7.2%) in second visit respectively. The frequency of
      complications was highest in younger than 25 year old age group. CONCLUSION:
      Having knowledge about these complications helps us to know which of them needs
      prompt medical intervention and which of them will resolve with time and just
      needs giving reassurance to the patient.

PMID- 24303397
TI  - Ossicular erosion in patients requiring surgery for cholesteatoma.
AB  - INTRODUCTION: The aim of this study was to evaluate the condition of the
      ossicular chain in patients requiring surgery for cholesteatoma. MATERIALS AND
      METHODS: In a retrospective analysis, the destruction of the individual and
      combined bony structures of the ear was described in 166 patients with
      cholesteatoma who went through surgery in our Otology Center between 2003 and
      2009. RESULTS: Total (55.4%) or partial (30.7%) erosion of the incus was the most
      common pathology. In some cases, the long process (25.9%) and the body of incus
      (4.8%) were also involved. Erosion of the stapes superstructure occurred more
      commonly than a total loss of the bone (40.9% vs. 25.9%). Erosion of the malleus
      was least common. Completely intact ossicles were present in 5.5% of cases. Total
      ossicular erosion with an intact footplate (18.7%) and incudostapedial erosion
      (18%) was the most common combination of ossicular erosion. All patients with
      incudostapedial erosion had advanced disease (85% with multiple site
      involvement). CONCLUSION: Widespread cholesteatoma results in greater ossicular
      erosion and poor hearing outcomes.

PMID- 24303398
TI  - Prevalence of hearing loss in newborns admitted to neonatal intensive care unit.
AB  - INTRODUCTION: Hearing is essential for humans to communicate with one another.
      Early diagnosis of hearing loss and intervention in neonates and infants can
      reduce developmental problems. The aim of the present study was to assess the
      prevalence of hearing impairment in newborns admitted to a neonatal intensive
      care unit (NICU) and analyze the associated risk factors. MATERIALS AND METHODS:
      This cross-sectional study was conducted to assess the prevalence of hearing loss
      in neonates who were admitted to the NICU at Nemazee Hospital, Shiraz University
      of Medical Sciences between January 2006 and January 2007. Auditory function was
      examined using otoacoustic emission (OAE) followed by auditory brainstem response
      (ABR) tests. Relevant potential risk factors were considered and neonates with a
      family history of hearing loss and craniofacial abnormality were excluded. For
      statistical analysis logistic regression, the chi-squared test, and Fisher's
      exact test were used. RESULTS: Among the 124 neonates included in the study, 17
      (13.7%) showed hearing loss in the short term. There was a significant
      statistical relationship between gestational age of less than 36 weeks (P=0.013),
      antibiotic therapy (P= 0.033), oxygen therapy (P=0.04), and hearing loss. On the
      contrary, there was no significant relationship between hearing loss and use of a
      ventilator, or the presence of sepsis, hyperbilirubinemia, congenial heart
      disease, transient tachypnea of newborn, congenital pneumonia, or respiratory
      distress syndrome. CONCLUSION: Auditory function in neonates who are admitted to
      a NICU, especially those treated with oxygen or antibiotics and those born
      prematurely, should be assessed during their stay in hospital. The importance of
      early diagnosis of hearing loss and intervention in these neonates and avoidance
      of any unnecessary oxygen or antibiotic therapy needs to be further promoted.

PMID- 24303399
TI  - Interest in Rhinoplasty and Awareness about its Postoperative Complications Among
      Female high School Students.
AB  - INTRODUCTION: Rhinoplasty is a popular cosmetic surgical procedure. Informal
      statistics show that Iran has one of the highest rates of rhinoplasty in the
      world. However, rhinoplasty like any other surgery can have complications.
      MATERIALS AND METHODS: In this cross-sectional study, 320 female students were
      selected by multistage cluster-stratified sampling from high schools in Kerman,
      Iran and each completed a questionnaire. RESULTS: More than half of the students
      said they would like to undergo rhinoplasty. The main reasons for wanting
      rhinoplasty were beauty and because it is fashionable. However, more than half of
      the interested students did not know about the possible postoperative
      complications of rhinoplasty. There was no relation between interest in having
      rhinoplasty and parents' education, city of birth or economic status. CONCLUSION:
      Many teenagers are interested in having rhinoplasty in Iran. As the number of
      teenagers and young adults who choose to have cosmetic surgery increases,
      surgeons should consider their expectations, motivations and awareness of
      postoperative complications before surgery.

PMID- 24303400
TI  - A bilateral pediculated palatal periosteal connective tissue flap for coverage of
      large bone grafts in the anterior maxillary region.
AB  - INTRODUCTION: Coverage of bone grafts is very important in reconstructive
      surgery. In edentulous alveolar ridges this coverage is particularly important
      for supporting dental prostheses. Here we present the case of a patient with a
      large deficient maxillary anterior region that was reconstructed with a bilateral
      palatal submucosal periosteal connective tissue flap: a soft tissue reserve for
      upper jaw reconstructive surgeries. The bilateral pediculated palatal periosteal
      connective tissue flap was used for coverage of a large bone graft in the
      anterior maxillary region. CONCLUSION: Palatal submucosa can be used as a soft
      tissue reserve in upper jaw reconstructions.

PMID- 24303401
TI  - An otogenic trapezius abscess: a case report.
AB  - INTRODUCTION: An otogenic brain abscess is a common ENT problem but an otogenic
      trapezius abscess can also be experienced in otolaryngological practice,
      particularly in patients with chronic suppurative otitis media. CASE REPORT: We
      report a rare case of a trapezius abscess in an eight-year-old girl who presented
      at the ENT, Head and Neck Surgery Postgraduate Medical Institute, Lady Reading
      Hospital, Peshawar, Pakistan on 15th December, 2010, with a presenting complaint
      of discharge from her right ear that had been occurring for the last five years.
      An exploration of the patient's right ear was performed, which showed that there
      was extensive cholesteatoma and tissue granulation tissues the antrum, attic and
      middle ear. The trapezius abscess had spread down to her back and was repeatedly
      drained. The patient was discharged on the 14th day following admission after
      making a complete recovery. After a regular follow-up period the child has
      remained disease free. The rare nature of this case prompted us to write this
      report. CONCLUSION: Chronic suppurative otitis media is a common clinical problem
      in developing countries. It can result in a number of complications if not
      treated properly. Although an otogenic trapezius abscess is a rare complication
      of chronic suppurative otitis media, it must be kept in mind.

PMID- 24303402
TI  - Missed Pharyngeal Foreign Body in an Infant that Persisted for 50 days:A Rare
      Case.

PMID- 24303403
TI  - Hair color and hearing loss: a survey in a group of military men.
AB  - INTRODUCTION: It has been shown that low levels of pigmentation increase
      susceptibility to noise-induced hearing loss in humans. For this reason, white
      populations develop more pronounced noise- induced hearing loss in comparison to
      black populations. Similarly, blue-eyed individuals exhibit greater temporary
      threshold shift than brown-eyed subjects; still, no strong correlation has been
      verified between the lightness of hair color and susceptibility to noise-induced
      hearing loss. This study was performed with the purpose of investigating a
      possible association between hair color and the degree of hearing loss due to
      firing noise. STUDY DESIGN: Prospective observational study. SETTING: A tertiary
      referral center with an accredited otorhinolaryngology-head & neck surgery
      department. MATERIALS AND METHODS: A total of 57 military recruits were divided
      into two groups; light-colored (blond and light brown) and dark-colored hair
      (dark brown and black). The two groups were matched based on history of firing
      noise exposure (number of rounds; type of weapon) and the level of hearing loss
      at 2, 3, 4, 6 and 8 kHz sound frequencies was compared between them. RESULTS: The
      results showed that the mean level of hearing loss of light-colored hair
      individuals (20.5+/-17dB) was significantly greater than that of dark-haired
      subjects (13.5+/-11dB), (P=0.023). CONCLUSION: The results indicate that hair
      color (blond versus black) can be used as an index for predicting susceptibility
      to noise-induced hearing loss in military environments. Therefore, based on the
      individual's hair color, upgraded hearing conservation programs are highly
      recommended.

PMID- 24303404
TI  - Evaluation of Tissue Expression and Salivary Levels of HER2/neu in Patients with
      Head and Neck Squamous cell Carcinoma.
AB  - INTRODUCTION: HER2/neu, a member of the epidermal growth factor receptor family,
      has been shown to be over-expressed in some tumors. The purpose of this study was
      to determine the salivary levels and tissue expression of HER2/neu in patients
      with head and neck squamous cell carcinoma (HNSCC) and their correlation with
      clinicopathologic parameters. MATERIALS AND METHODS: Enzyme-linked immunosorbent
      assays (ELISA) were used to evaluate the salivary levels of HER2/neu and
      immunohistochemistry was used to measure tissue expression of HER2/neu in 28
      patients with HNSCC and 25 healthy control subjects. RESULTS: The salivary levels
      of HER2/neu in patients with HNSCC were not significantly higher compared to
      healthy control subjects. There was no apparent correlation between salivary
      HER2/neu levels and clinicopathological features such as age, sex, tumor grade,
      tumor size and nodal status. All HNSCC specimens were positive (membranous or/and
      cytoplasmic) for HER2/neu, except one sample. Only one HNSCC specimen showed
      staining purely in the tumor-cell cytoplasm. All control specimens were also
      positive for both membranous and cytoplasmic HER2/neu but there was a significant
      difference between the level of cytoplasmic staining in the HNSCC specimens and
      in the control specimens (P<0.05). CONCLUSION: In our study, no overexpression of
      HER2/neu was observed. Thus, identification of HER2/neu levels plays no role in
      differentiating between normal and squamous cell carcinoma tissues or detecting
      the carcinogenesis process. Our findings suggest that the use of HER2/neu as a
      salivary marker of HNSCC is not recommended, because no significant preoperative
      elevation and no association with clinicopathological features were found.

PMID- 24303405
TI  - A study of the etiology of referred otalgia.
AB  - INTRODUCTION: Otalgia is one of the complaints which may occur at any age. The
      etiology of the pain may be in the ear, structures around the ear or other head
      and neck structures. This is caused by the complex nervous connections in the
      head and neck areas, the ear, the pharynx and the nose. Since understanding the
      etiologies of referred otalgia can help in the assessment and treatment of the
      disease, this research was conducted to identify the etiologies of referred
      otalgia in patients visiting the ENT Clinic in Gorgan, Iran. MATERIALS AND
      METHODS: This prospective research was conducted on patients who visited the ENT
      Clinic with an earache, but in initial assessments the ear was normal. Patients'
      data consisting of sex, age, complaint, the inflicted side, physical findings in
      the ear, the nose, the throat and head and neck were recorded in a questionnaire.
      These data were then analyzed with SPSS software. RESULTS: Of 770 patients with
      otalgia, 94 patients (12.2%) had referred otalgia. Of these patients 27.7% were
      men and 72.3% were women. The most common etiology of referred otalgia was dental
      problems (62.8%), and one patient who was being treated for pharyngitis had
      carcinoma of the base of the tongue. In 47.8% of cases the pain was in the left
      ear, in 43.4% in the right ear, and in 8.7% it was bilateral. CONCLUSION: In view
      of the fact that a significant proportion of the patients who complained of
      otalgia had no pathologies in the ear, thorough physical examination in adjacent
      structures especially teeth should be performed and malignancies should be
      considered as a possible etiology of otalgia.

PMID- 24303406
TI  - Complications requiring cochlear reimplantation.
AB  - INTRODUCTION: Surgery for revision of cochlear implantation is an unusual but not
      uncommon occurrence. The purpose of this study was to discuss the major
      complications of cochlear implantation that we observed in 11out of 275 patients
      who underwent cochlear implantation in Khalili Hospital at Shiraz University of
      Medical Sciences. MATERIALS AND METHODS: A retrospective analysis of 275patients
      who underwent cochlear implantation between 2003 and 2009 was performed. All of
      the patients were followed for one to five years. RESULTS: Only 11 patients
      needed to undergo revision surgery or take medication. Out of those, five
      patients were referred with signs of device failure, all of whom underwent
      reimplantation. For the rest of the patients with complications, one patient
      underwent surgery due to a misplaced electrode, two patients had poor telemetry
      due to migration of the implant magnet, one patient presented with meningitis
      that was managed by medical treatment, and two patients presented with a massive
      scalp hematoma that responded to medical treatment. CONCLUSIONS: In our study the
      most common cause of a need for cochlear reimplantation was device failure.

PMID- 24303407
TI  - Otological findings ten years after myringotomy with tympanostomy tube insertion.
AB  - INTRODUCTION: To study the long-term complications of tympanostomy tube insertion
      in young children 10 years after surgery. MATERIALS AND METHODS: In September
      2011, the medical records of all patients who had undergone myringotomy with
      tympanostomy tube insertion between February 2000 and March 2001 at the two
      general hospitals of Isfahan University of Medical Sciences were studied. Of the
      98 patients who fulfilled the inclusion criteria, 82 patients agreed to
      participate and were enrolled in the study. The complications of the operation
      were evaluated in these patients. RESULTS: Of the 164 ears that were operated on,
      myringosclerosis was found in 17.1%, atrophy of the tympanic membrane in 1.2%,
      permanent perforation of the tympanic membrane in 0.6% and tympanic membrane
      atelectasis in 0.6%. None of the patients developed cholesteatoma as a
      complication of tympanostomy tube insertion. CONCLUSION: Considering the low risk
      of serious complications after 10 years, tympanostomy tube insertion is a safe
      and effective treatment option in the treatment of otitis media with effusion.

PMID- 24303408
TI  - Maternal risk factors for oral clefts: a case-control study.
AB  - INTRODUCTION: A cleft lip with or without a cleft palate is one of the major
      congenital anomalies observed in newborns. This study explored the risk factors
      for oral clefts in Gorgan, Northern Iran. MATERIALS AND METHODS: This hospital
      based case-control study was performed in three hospitals in Gorgan, Northern
      Iran between April 2006 and December 2009. The case group contained 33 newborns
      with oral clefts and the control group contained 63 healthy newborns. Clinical
      and demographic factors, including date of birth, gender of the newborns, type of
      oral cleft, consanguinity of the parents, parental ethnicity, and the mother's
      parity, age, education and intake of folic acid were recorded for analysis.
      RESULTS: A significant association was found between parity higher than 2 and the
      risk of an oral cleft (OR= 3.33, CI 95% [1.20, 9.19], P> 0.02). According to
      ethnicity, the odds ratio for oral clefts was 0.87 in Turkmens compared with
      Sistani people (CI 95% [0.25, 2.96]) and 1.11 in native Fars people compared with
      Sistani people (CI 95% [0.38, 3.20]). A lack of folic acid consumption was
      associated with an increased risk of oral clefts but this was not statistically
      significant (OR = 1.42, CI 95% [0.58, 3.49]). There were no significant
      associations between sex (OR boy/girl = 0.96, CI 95% [0.41, 2.23]), parent
      familial relations (OR = 1.07, CI 95% [0.43, 2.63]), mother's age and oral
      clefts. CONCLUSIONS: The results of this study indicate that higher parity is
      significantly associated with an increased risk of an oral cleft, while Fars
      ethnicity and a low intake of folic acid increased the incidence of oral clefts
      but not significantly.

PMID- 24303409
TI  - Multiple congenital epulis of the mandibular ridge: a case report.
AB  - Congenital epulis is a very rare benign soft-tissue tumor of uncertain
      histogenesis, which is also known as "gingival granular cell tumor of the
      newborn". It occurs almost exclusively as a single tumor along the alveolar ridge
      of the maxilla in newborn females. Although congenital epulis is strikingly
      similar to the more common adult granular cell tumor histologically, in contrast
      to the latter congenital epulis cells are negative for S-100 protein. This case
      report describes a 15-day-old female infant with multiple congenital epulis of
      the mandibular alveolar ridge. 

PMID- 24303410
TI  - Platelet-rich fibrin: an autologous fibrin matrix in surgical procedures: a case
      report and review of literature.
AB  - INTRODUCTION: The healing process after surgery is a challenging issue for
      surgeons. Various materials and techniques have been developed to facilitate this
      process and reduce its period. Fibrin adhesives are often used in cardiothoracic
      and vascular surgery to seal diffuse microvascular bleeding and in general and
      plastic surgery to seal wound borders. This Case report and literature review
      will introduce the various usages of platelet-rich fibrin in different surgical
      procedures and the method of producing the matrix. CASE REPORT: A 24-year old man
      with periorbital skin avulsion treated with PRF membrane has been reported and
      discussed in this paper. CONCLUSION: Platelet-rich fibrin is a natural autologous
      fibrin matrix, which can be produced with a simple blood sample and a table
      centrifuge. The material has been used in a wide range of surgical procedures to
      shorten the healing period and reduce post-surgical complications.

PMID- 24303411
TI  - A broken metallic tracheostomy tube.

PMID- 24303412
TI  - Comparison of Local Anesthetic Effect of Bupivacaine versus Bupivacaine plus
      Dexamethasone in Nasal Surgery.
AB  - INTRODUCTION: Adequate pain control is an important consideration in the post
      surgical management of patients. Local nerve blockade added to general anesthesia
      can provide excellent pain control during and after most nasal surgical
      procedures. The aim of this study was to determine the combined effect of local
      anesthetic drugs with corticosteroids in nasal surgery. MATERIALS AND METHODS: In
      this double-blind clinical study, 60 patients who underwent different nasal
      surgical procedures were matched and divided into two equal groups. Bilateral
      local nerve blockade was used in both groups. Bupivacaine or bupivacaine plus
      dexamethasone was administered by injection (groups B and B+D, respectively).
      Postoperative visual analog scale (VAS) pain values and the need for
      oral/intramuscular analgesic treatment in the first 24 h were recorded in all
      patients. RESULTS: Thirty-eight male (63.3%) and 22 female (36.7%) patients were
      included in this study, with a mean age of 28.3 +/- 8.2 years. At 1, 2, 4, 6, and
      12 h post surgery, VAS pain values were significantly lower in the B+D group than
      in the B group. The analgesic requirement was significantly lower in the B+D
      group compared with the B group. No relevant complications were seen during
      surgery or postoperative hospitalization.

PMID- 24303413
TI  - Comparison of sinonasal symptoms in patients with nasal septal deviation and
      patients with chronic rhinosinusitis.
AB  - INTRODUCTION: Disorders of the nose and paranasal sinuses are among the most
      common chronic illnesses. Although considerable progress has been made in the
      medical and surgical control of these diseases, a large number of questions
      relating to the diagnosis, evaluation, and treatment of these conditions remain
      unanswered. The aim of the present study was to evaluate differences in the
      frequency of symptoms and disease severity in patients with nasal septal
      deviation (NSD) compared with chronic rhinosinusitis (CRS). MATERIALS AND
      METHODS: A total of 156 patients, divided into NSD and CRS groups, were studied
      in relation to symptoms and disease severity. Patients were selected from those
      referred to the Ear, Nose, and Throat (ENT) Wards of the Imam Reza and Ghaem
      Hospitals, who had not responded to a variety of treatments. Depending on the
      type of disease, patients were candidates for either septoplasty or endoscopic
      sinus surgery. The Rhinosinusitis Symptom Inventory was administered to measure
      the severity of symptoms, with scores assigned based on the answers given by
      patients (Likert scale). Scores were compared between the CRS and NSD groups.
      RESULTS: A total of 156 patients (78 with NDS and 78 with CRS) entered the study
      in overall sinonasal symptoms were more prevalent in CRS group. Nasal congestion,
      runny nose, earache, toothache, and smelling disorder were significantly more
      common in the CRS group (P<0.001); while there were no significant differences in
      symptoms such as facial pressure, fever, or headache between the two groups
      (P>0.05). CONCLUSION: Patients with CRS manifested statistically significantly
      greater sinonasal symptom scores than patients with NSD.

PMID- 24303414
TI  - Submental intubation in maxillofacial trauma patients.
AB  - INTRODUCTION: To describe a modified technique for submental intubation in
      severely traumatized maxillofacial patients and to evaluate complications arising
      from the procedure. MATERIALS AND METHODS: Submental intubation was performed in
      twelve patients with maxillofacial trauma ,from 2007-2012, which were operated
      under general anesthesia for treatment of facial fractures. RESULTS: The patients
      ranged in age from 14 to 39 years. No complications due to submental intubation,
      such as infection, hypertrophic scarring, lingual nerve injury, hematoma,
      bleeding, ranula formation, or orocutaneous fistula, were observed following
      submental intubation. CONCLUSION: Submental intubation is a very useful technique
      in the management of maxillofacial trauma patients, with a low complication rate.

PMID- 24303415
TI  - Combined intratympanic and systemic steroid therapy for poor-prognosis sudden
      sensorineural hearing loss.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of combined
      intratympanic and systemic steroid therapy compared with systemic steroid therapy
      alone in idiopathic sudden sensorineural hearing loss (ISSNHL) patients with poor
      prognostic factors. MATERIALS AND METHODS: Seventy-seven patients with sudden
      sensorineural hearing loss (SSNHL) who had at least one poor prognostic factor
      (age greater than 40 years, hearing loss more than 70 db, or greater than a 2
      week delay between the onset of hearing loss and initiation of therapy) were
      included in this study. Patients were randomized to the intervention group
      (combined intratympanic and systemic steroid therapy) or the control group
      (systemic steroid therapy alone). All patients received oral treatment with
      systemic prednisolone (1 mg/kg/day for 10 days), acyclovir (2 g/day for 10 days,
      divided into four doses), triamterene H (daily), and omeprazole (daily, during
      steroid treatment), and were advised to follow a low salt diet. The intervention
      group also received intratympanic dexamethasone injections (0.4 ml of 4 mg/ml
      dexamethasone) two times a week for two consecutive weeks (four injections in
      total). A significant hearing improvement was defined as at least a 15-db
      decrease in pure tone average (PTA). RESULTS: Among all participants,44
      patients(57.14%) showed significant improvement in hearing evaluation. More
      patients showed hearing improvement in the intervention group than in the control
      group (27 patients (75%) versus 17 patients (41.4%), respectively; P=0.001).
      CONCLUSION: The combination of intratympanic dexamethasone and systemic
      prednisolone is more effective than systemic prednisolone alone in the treatment
      of poor-prognosis SSNHL.

PMID- 24303416
TI  - Surgical removal of neglected soft tissue foreign bodies by needle-guided
      technique.
AB  - INTRODUCTION: The phenomenon of neglected foreign bodies is a significant cause
      of morbidity in soft tissue injuries and may present to dermatologists as delayed
      wound healing, localized cellulitis and inflammation, abscess formation, or
      foreign body sensation. Localization and removal of neglected soft tissue foreign
      bodies (STFBs) is complex due to possible inflammation, indurations, granulated
      tissue, and fibrotic scar. This paper describes a simple method for the quick
      localization and (surgical) removal of neglected STFBs using two 23-gauge needles
      without ultrasonographic or fluoroscopic guidance. MATERIALS AND METHODS: A
      technique based on the use of two 23-gauge needles was used in 41 neglected STFBs
      in order to achieve proper localization and fixation of foreign bodies during
      surgery. RESULTS: Surgical removal was successful in 38 of 41 neglected STFBs
      (ranging from 2-13mm in diameter). CONCLUSION: The cross-needle-guided technique
      is an office-based procedure that allows the successful surgical removal of STFBs
      using minimal soft tissue exploration and dissection via proper localization,
      fixation, and propulsion of the foreign body toward the surface of the skin.

PMID- 24303417
TI  - The effect of adenotonsillectomy on pediatric nocturnal enuresis: a prospective
      cohort study.
AB  - INTRODUCTION: Sleep disorder caused by adenotonsillar hypertrophy has been
      implicated as a cause of primary and secondary nocturnal enuresis in children.
      This study was conducted to investigate the effect of adenotonsillectomy on
      enuresis in children with adenotonsillar hypertrophy. MATERIALS AND METHODS: This
      prospective cohort study was conducted in Hamadan City in Western Iran, from
      April 2010 to December 2011. Ninety-seven children aged 3 to 12 years with
      adenotonsillar hypertrophy who were admitted to Besat Hospital for
      adenotonsillectomy were evaluated. The primary outcome was the number of
      incidents of bedwetting (nocturnal enuresis) post-operation compared with pre
      operation. Patients were followed-up for 3 months. Data were collected using a
      questionnaire regarding number of bedwetting incidents, type of enuresis (primary
      or secondary), and family history of enuresis, as well as results of urine
      analysis. RESULTS: Of 420 children admitted for adenotonsillectomy, 97 had a
      positive history of preoperative enuresis, including 42 girls and 55 boys, with
      mean age of 48 months. The parents of 84 (86.6%) children agreed to participate
      in the study. Three months after adenotonsillectomy, enuresis had resolved
      completely in 51 (60.7%) children and had shown relative improvement in 22
      (26.2%) children. Enuresis had not improved in the remaining 11 (13.1%) children
      (P<0.001). CONCLUSION: The results of this study indicate that adenotonsillectomy
      can improve enuresis in the majority of children with adenotonsillar hypertrophy.
      However, further evidence based on large multi-center randomized clinical trials
      is required to confirm these results.

PMID- 24303418
TI  - Effects of parental education level and economic status on the needs of families
      of hearing-impaired children in the aural rehabilitation program.
AB  - INTRODUCTION: The family of each hearing-impaired child has its own cultural,
      social, educational, and financial background, and its own special needs. The
      objectives of our study were to explore the information and support needs of
      parents of children with severe-to-profound hearing impairment and to investigate
      the effects of the parents' level of education and economic status on the score
      attained in the parents'-needs questionnaire. MATERIALS AND METHODS: Fifty-one
      parents of children with severe-to-profound hearing loss (53% girls, 47% boys;
      mean age 47.96 months) who used the Auditory-Verbal Therapy approach were asked
      to complete the parents'-needs questionnaire. The questionnaire included
      demographic information and hearing-loss history and covered six domains which
      evaluated the information or support needs of parents. Parental needs with regard
      to different domains were evaluated separately in all participants. RESULTS:
      Statistical analysis indicated that there was a significant decrease in the score
      attained in the parents'-needs questionnaire with increasing level of education
      of the child's parents (P<0.0001). Furthermore, the questionnaire score decreased
      as the parents' economic status increased (P<0.0001). CONCLUSION: The results of
      our study indicate that most parents of hearing-impaired children need adequate
      and appropriate information in all domains, and these findings support the
      positive effect of creating an appropriate educational environment by considering
      individualized needs. Furthermore, parents' levels of education and economic
      status have a significant effect on their parents' needs.

PMID- 24303419
TI  - Isolated laryngeal amyloidosis.
AB  - INTRODUCTION: Amyloidosis comprises a heterogeneous group of disorders
      characterized by the deposition of amyloid protein in various organs of the body.
      The larynx is one of the rarer sites where amyloidosis occurs. CASE REPORT: A 36
      year-old man presented with a two-year history of hoarseness of voice. He had a
      positive history of smoking, but no history of long-term consumption of alcohol.
      Physical examination revealed a pinkish mass about 1.5* 1.5 cm in size on his
      left False Vocal Cord (FVC) extending to the left arytenoid, which resulted in
      asymmetry of the posterior larynx. He also had a chronic perforation of the right
      tympanic membrane with a conductive hearing loss consisting of a 50 dB gap in
      pure tune audiometry. The FVC mass was excised with a CO2 laser and on follow-up
      his voice got much better, but the hoarseness was not fully resolved. CONCLUSION:
      Amyloidosis of the larynx is a rare, usually benign process but the area is the
      most common site for isolated amyloid deposits to occur in the head and neck.

PMID- 24303420
TI  - Nasal Septum Perforation due to Methamphetamine abuse.
AB  - INTRODUCTION: Spontaneous Perforation of the nasal septum is an uncommon
      condition. Nasal inhalation of substances such as cocaine has long been linked to
      this Perforation. CASE REPORT: This report describes the case of a 46-year-old
      woman who was addicted to methamphetamine and who presented with perforation of
      the nasal septum.This is the first reported case of nasal septal necrosis linked
      to nasal inhalation of methamphetamine. CONCLUSIONS: Patient history and
      assurance regardingillegal drug consumption and abuse is a key point for fast and
      accurate diagnosis. The pathophysiology of drug-induced sinunasal disease and a
      review of the literature are also presented.

PMID- 24303421
TI  - Taping after rhinoplasty for asian noses.

PMID- 24303422
TI  - Endoscopic middle ear and mastoid surgery for cholesteatoma.
AB  - INTRODUCTION: To reduce incidence of residual cholesteatoma following ear
      surgery; and to reduce the need for second look "open" mastoidectomy using
      endoscopic mastoidotomy. Ten-year retrospective chart review of 249 primary
      cholesteatoma cases (1994-2004) with a minimum follow-up of two years. The first
      objective was to evaluate the effectiveness of otoendoscopy in reducing the
      incidence of "cholesteatoma remnant" at the time of primary surgery. The second
      investigation was to evaluate the effectiveness of otoendoscopy in reducing the
      need to open the mastoid cavities during "second look operations". MATERIALS AND
      METHODS: Endoscopes were used on all cases as an adjunct to standard microscopic
      methods. Once all visible cholesteatoma was removed with standard microscopic
      techniques, endoscopes were utilized in order to identify any "remnants" of
      cholesteatoma. Endoscopes were also employed during revision second look cases in
      order to allow the evaluation of intact canal wall mastoid cavities without an
      open Mastoidectomy approach. RESULTS: Endoscopy at time of primary operations
      revealed a 22% incidence of hidden cholesteatoma "remnants" despite apparent
      total microscopic eradication in closed cavity cases, and 10% in open cavity
      patients. Endoscopic removal of cholesteatoma remnants reduced the long term
      cholesteatoma "residual" to 9.7% in closed cavity patients. Furthermore,
      endoscopic surgery significantly reduced the need to open the mastoids during
      second look operations. CONCLUSION: Otoendoscopy is a very effective adjunctive
      method in ear surgery. It allows significant reduction in cholesteatoma residual
      rate in both closed cavity and open cavity cases. Furthermore, the great majority
      of second look mastoids can be evaluated endoscopically and thus avoid an open
      revision Mastoidectomy.

PMID- 24303423
TI  - Assessment of Septoplasty Effectiveness using Acoustic Rhinometry and
      Rhinomanometry.
AB  - INTRODUCTION: Septal deviation is the chief cause of chronic nasal obstruction.
      In order to treat such cases, nasal septoplasty surgery is usually performed
      based on patient complaints and a surgeon's examination, both of which are
      subjective. This study aims at using the objective parameters of acoustic
      rhinometry and rhinomanometry to evaluate the effectiveness of septoplasty
      surgery. MATERIALS AND METHODS: A prospective study was performed in 30 candidate
      patients for septoplasty surgery. Acoustic rhinometry and rhinomanometry tests
      were performed on all patients both before and 3 months after the operation. The
      symptom recovery rate was recorded according to the patient's statements and
      anterior rhinoscopic examinations 3 months after surgery. Data were analyzed
      using a t-test and chi-square tests in a SPSS package. RESULTS: A total of 26 of
      30 patients returned for a post-procedure follow-up examination after 3 months.
      Patients were aged from 18 to 32 years (average, 25 years). In total 69.2% (18
      patients) were satisfied with the results of the procedure. In addition,
      rhinomanometry resulted in a decrease in general nasal resistance if patients
      used decongestants (P=0.03). However, the decrease was not significant before the
      use of decongestants (P=0.12). Furthermore, according to the results from
      acoustic rhinomanometry, there was an increase in the nasal cross-sectional area
      on both the narrow and wide sides after the operation (P<0.05), although this
      increase was not so notable in the narrower side after using decongestants. There
      was, however, no significant relationship between the results from the objective
      tests and the patient's symptoms or clinical examinations (P>0.05). CONCLUSION:
      The findings of this study show that although the objective tests confirm an
      improvement in general nasal resistance and an increase in the nasal cross
      sectional area after surgery, no unambiguous relationship between the patient's
      symptoms and the clinical examinations is observed. Therefore, such objective
      tests do not prove to be sufficient diagnostic criteria for the effectiveness of
      septoplasty.

PMID- 24303424
TI  - Survey on the prevalence of allergic rhinitis and its effect on the quality of
      high school students' life.
AB  - INTRODUCTION: Allergic rhinitis (AR) is a common airway disease. In order to
      study the prevalence of AR in high school students in Kerman, the Score for
      Allergic Rhinitis (SFAR) was used and the quality of life in the students
      affected by rhinitis was evaluated using the SF-36 questionnaire. MATERIALS AND
      METHODS: This was a cross-sectional, analytical, descriptive study, based on the
      SFAR scale. Quality of life in students with AR was evaluated using the SF-36
      questionnaire. RESULTS: From 1511 students who completed the SFAR questionnaire,
      291 (52.6%, girls; 47.4%, boys) had AR. Domestic dust was the most common cause
      of the disease. The most common symptoms of AR were rhinorrhea (76.6%), epiphora
      (76.3%), nasal congestion (64.3%), and itching (54.3%). According to the ARYA
      scale, (Allergic Rhinitis and its Impact on Asthma), 41.9% of students had
      moderate-to-severe rhinitis and 58.1% had mild rhinitis. A total of 43.1% of
      patients with moderate-to-severe rhinitis had a persistent condition and 56.9%
      had an intermediate condition. Results of the SF-36 questionnaire among students
      with AR showed a significant difference in physical functioning and bodily pain
      in comparison with healthy students. CONCLUSION: The results of this study show
      that the prevalence of AR among Kerman high school students is 19.3%. Because of
      the effect of this disease on the life quality of high school students in terms
      of both physical functioning and bodily pain, efforts should be made to reduce
      allergen levels as far as possible.

PMID- 24303425
TI  - Topical application of mitomycin C in the treatment of granulation tissue after
      canal wall down mastoidectomy.
AB  - INTRODUCTION: Otorrhea and granulation tissue in Canal Wall Down mastoidectomy
      (CWD) is the common problem in cholesteatoma removal and leads to many discomfort
      for both the patient and the physician. The main objective in CWD is creating the
      dry cavity, so the topical antibiotic and acetic acid in variable saturations are
      used for this purpose. In this study we evaluate the effectiveness of topical MMC
      and chemical cautery by acetic acid. MATERIALS AND METHODS: Study population
      consists of 50 patients with cholesteatoma whom underwent CWD. All patient
      allocated randomly in two study groups, MMC and acetic acid. After 3 weeks, the
      first visit is planned, extension of granulation tissue and dryness of cavity are
      evaluated and topical drugs are used in blind fashion. MMC in 4% and acetic acid
      in 12.5% saturation are applied. Other visits are completed at next month and 3
      months later. RESULTS: Both methods are effective in treatment of granulation
      tissue. In each group both treatment were effective too but MMC was more
      effective than acid acetic in the treatment of granulation tissue after 4 weeks.
      CONCLUSION: Based on our findings, it is clear that topical MMC is very effective
      in the treatment of granulation tissue and in CWD. It results in dry cavity much
      better than acetic acid without any complication.

PMID- 24303426
TI  - Music training program: a method based on language development and principles of
      neuroscience to optimize speech and language skills in hearing-impaired children.
AB  - INTRODUCTION: In recent years, music has been employed in many intervention and
      rehabilitation program to enhance cognitive abilities in patients. Numerous
      researches show that music therapy can help improving language skills in patients
      including hearing impaired. In this study, a new method of music training is
      introduced based on principles of neuroscience and capabilities of Persian
      language to optimize language development in deaf children after implantation.
      MATERIALS AND METHODS: The candidate children are classified in three groups
      according to their hearing age and language development. The music training
      program is established and centered on four principles, as follows: hearing and
      listening to music (with special attention to boost hearing), singing, rhythmic
      movements with music and playing musical instruments. RESULTS: Recently much
      research has demonstrated that even after cochlear implant operation, a child
      cannot acquire language to the same level of detail as a normal child. As a
      result of this study music could compensate this developmental delay .It is known
      that the greater the area of the brain that is activated, the more synaptic
      learning and plasticity changes occur in that specific area. According to the
      principles of neural plasticity, music could improve language skills by
      activating the same areas for language processing in the brain. CONCLUSION: In
      conclusion, the effects of music on the human brain seem to be very promising and
      therapeutic in various types of disorders and conditions, including cochlear
      implantation.

PMID- 24303427
TI  - Alterations in the Contra lateral Ear in Chronic Otitis Media.
AB  - INTRODUCTION: Chronic otitis media (COM), a persistent and durable inflammation
      and infection of the middle ear, is a common disorder. Alterations in the
      contralateral ear in sufferers have been observed in recent years. Because only a
      few studies have been reported in this area, we performed this study in order to
      assess alterations in the contralateral ear of patients with COM. MATERIALS AND
      METHODS: Cross-sectional and descriptive methods were used in 100 patients with
      COM who were selected for surgical treatment and admitted to hospital. An
      information form was completed for all patients including demographic data,
      medical history of otoscopy and paraclinical examinations such as pure tone
      audiometry (PTA), tympanometry, Schuller radiography, and high resolution
      computed tomography (HRCT). All data were processed using SPSS (version 18)
      software and descriptive statistical tests. RESULTS: According to otoscopy, PTA,
      tympanometry and graphical analysis, 60% of patients experienced disorders of the
      contralateral ear. Otoscopy analysis showed 54% of patients had a disorder of the
      contralateral ear, with the most common disorder being perforation of the ear
      drum. PTA showed a 48% incidence of contralateral ear problems (85% conductive
      hearing impairment; 12.5% sensorineural hearing impairment; 1.2% mixed). A total
      of 73.2% of patients with conductive hearing loss had a problem across all
      frequencies, while half of the patients with sensorineural hearing impairment had
      problems at frequencies greater than 1000 Hz. According to tympanometry, 38% of
      patients had problem in the contralateral ear. HRCT and Schuller graphical
      analyses indicated 31.5% and 36% occurrence of contralateral ear disorders,
      respectively. CONCLUSION: More than 50% of patients with COM in one ear have a
      chance of also presenting with the disease in the other ear. Outcomes of this
      study and previous studies have shown that COM should not be perceived as a
      disease limited to one ear, because in most cases the progress of the disease can
      affect both ears.

PMID- 24303428
TI  - Quality of life, pulmonary spirometry, and dosage of steroid in asthmatic
      patients with polyposis after endoscopic sinus surgery.
AB  - INTRODUCTION: The association between asthma and sinonasal disease has been
      established for years. As sinonasal disease is one of the factors that
      exacerbates asthma, effective treatment of this disorder may also improve and
      stabilize the asthmatic condition. This study examines the outcome of endoscopic
      sinus surgery (ESS) on asthmatic patients with massive nasal polyposis. MATERIALS
      AND METHODS: Forty-five asthmatic patients were included in the study. All were
      operated on and analyzed in our department. A questionnaire (SNOT-20)
      investigating the subjective evaluation of asthma and sinonasal states was
      presented to the patients, while objective evaluations including nasal
      rhinoscopy, forced expiratory volume in 1 second (FEV1), and steroid use were
      conducted with 1-2 years of follow up. RESULTS: Quality of life (QoL) improved in
      97.8% of patients, while clinical symptoms, emotional signs, and social signs
      improved in 97.7%, 84.4%, and 93.3%, respectively. Medication use for asthma
      showed a similar improvement, with approximately 80% of patients reducing and
      75.6% of patients discontinuing steroid use. A total of 91.1% of patients showed
      improvement in post-operative FEV1. CONCLUSION: ESS achieved a beneficial effect
      on sinonasal and asthma symptomatology in patients with nasal polyps and asthma.
      QoL was also improved in these patients.

PMID- 24303429
TI  - Effect of infant prematurity on auditory brainstem response at preschool age.
AB  - INTRODUCTION: Preterm birth is a risk factor for a number of conditions that
      requires comprehensive examination. Our study was designed to investigate the
      impact of preterm birth on the processing of auditory stimuli and brain
      structures at the brainstem level at a preschool age. MATERIALS AND METHODS: An
      auditory brainstem response (ABR) test was performed with low rates of stimuli in
      60 children aged 4 to 6 years. Thirty subjects had been born following a very
      preterm labor or late-preterm labor and 30 control subjects had been born
      following a full-term labor. RESULTS: Significant differences in the ABR test
      result were observed in terms of the inter-peak intervals of the I-III and III-V
      waves, and the absolute latency of the III wave (P<0.019). No significant
      differences were observed in the amplitude of the I or V waves. The choice of
      test ear examined had no effect on the results. CONCLUSION: Our results indicate
      an effect of preterm birth on ABRs and synchronization of auditory stimuli at
      preschool age, and suggest the need for further follow-up over the coming years.

PMID- 24303430
TI  - Nodular fasciitis of the auricle: a case report.
AB  - INTRODUCTION: Nodular fasciitis is described as a benign reactive proliferation
      of myofibroblasts. Due to its rapid-growing nature, a precise clinical diagnosis
      is difficult and the condition is frequently misdiagnosed as malignant lesions.
      CASE REPORT: In this study, we present the case of a young woman with an
      auricular nodular fasciitis as an example of one of the rarest sites of this
      tumor. The patient underwent an excision of the lesion under general anesthesia.
      The literature choices for treatment include complete excision, partial excision,
      or intralesional injection of steroids. Due to its associated local discomfort,
      and in order to exclude other differential diagnosis, we recommend a complete
      surgical excision. CONCLUSION: Auricular nodular fasciitis is a rare lesion. Due
      to its associated local discomfort, and in order to exclude other differential
      diagnosis, we recommend a complete surgical excision.

PMID- 24303431
TI  - Orbital Extension of a Giant Ethmoidal Sinus Osteoma in a 30-Year-old Female.
AB  - INTRODUCTION: Osteoma is a benign tumor rarely found in the paranasal sinuses.
      CASE REPORT: A 30-year-old female presented with an 8-month history of proptosis
      of the right eye that was progressing slowly. She was diagnosed with ethmoid
      osteoma and managed with collaborative surgery at the ophthalmology and
      otolaryngology departments. After surgery, the patient suffered visual loss that
      was managed medically. The surgical steps and protocol used for safe removal are
      discussed in the report. CONCLUSION: Management of a giaint osteoma extending to
      orbital tissue needs meticulous dissection through open approach and
      collaborative surgery by otolaryngologist and ophthalmologist.

PMID- 24303432
TI  - The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin
      Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia.
AB  - INTRODUCTION: Neonatal hyperbilirubinemia is one of the most important factors
      affecting the auditory system and can cause sensorineural hearing loss. This
      study investigated the relationship between behavioral hearing thresholds in
      children with a history of jaundice and the maximum level of bilirubin
      concentration in the blood. MATERIALS AND METHODS: This study was performed on 18
      children with a mean age of 5.6 years and with a history of neonatal
      hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and
      brainstem evoked responses were evaluated in all children. RESULTS: Six children
      (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree
      of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between
      the mean total bilirubin levels and behavioral hearing thresholds in all samples.
      A transient evoked emission was seen only in children with normal hearing
      thresholds however in eight cases brainstem evoked responses had not detected.
      CONCLUSION: Increased blood levels of bilirubin at the neonatal period were
      potentially one of the causes of hearing loss. There was a lack of a direct
      relationship between neonatal bilirubin levels and the average hearing thresholds
      which emphasizes on the necessity of monitoring the various amounts of bilirubin
      levels.

PMID- 24303433
TI  - Effects of Peritonsillar Injection of Tramadol and Adrenaline before
      Tonsillectomy.
AB  - INTRODUCTION: Various hemostatic and analgesic agents and techniques have been
      used to reduce intraoperative and postoperative hemorrhage and pain in
      tonsillectomy.Aims and objective; The current study aimed to compare the effect
      of using adrenaline plus tramadol and normal saline in maintaining hemostasis and
      control of pain in cold dissection tonsillectomy. MATERIALS AND METHODS: This
      prospective randomized study was conducted over a period of 10 months in
      department of otorhinolaryngology state medical college Srinagar. In the current
      study 46 patients planed for tonsillectomy were put into two groups. 23 patients
      in each group. In group A patients (study group) 4ml of solution containing
      1:200000 adrenaline and 2mg/kg tramadol was injected in peritonsillar space. In
      group B patients (control group) 4ml of normal saline was injected in
      peritonsillar space. RESULTS: It was found that the time required to achieve
      heamostasis and post operative pain was less in group A patients in comparison to
      Group B patients. There was no significant side effect or complications when
      adrenaline and tramadol were used. CONCLUSION: Large randomized controlled
      studies are needed to compare tramadol plus adrenaline infiltration with other
      heamostatic and analgesics, but the current study indicated that Tramadol plus
      adrenaline infiltration could be an effective method to reduce the post operative
      pain , operative time and time to achieve heamostasis in tonsillectomy surgeries.
      Therefore the use of Tramadol plus adrenaline infiltration should be further
      promoted and implemented as routine use in tonsillectomy surgeries.

PMID- 24303434
TI  - Vestibular Evoked Myogenic Potential Produced by Bone-Conducted Stimuli: A Study
      on its Basics and Clinical Applications in Patients with Conductive and
      Sensorineural Hearing Loss and a Group with Vestibular Schawannoma.
AB  - INTRODUCTION: Vestibular evoked myogenic potential (VEMP) has recently been
      broadly studied in vestibular disorders. As it is evoked by loud sound
      stimulation, even mild conductive hearing loss may affect VEMP results. Bone
      conducted (BC) stimulus is an alternative stimulation for evoking this response.
      This study aims to assess the characteristics of BC-VEMP in different groups of
      patients. MATERIALS AND METHODS: We performed a cross sectional analysis on 20
      healthy volunteers with normal pure-tone audiometry as a control group; and on a
      group of patients consisted of 20 participants with conductive hearing loss, five
      with bilateral sensorineural hearing loss and four with vestibular schawannoma.
      AC and BC-VEMP were performed in all participants. RESULTS: In control group the
      VEMP responses to both kinds of stimuli had an acceptable morphology and
      consisted of p13 and n23 waves. Latency value of these main components in each
      type of stimulus was not significantly different (P>0.05). However, the mean
      amplitude was larger in BC modality than AC stimulation (P=0.025). In the group
      with conductive hearing loss, the VEMP response was absent in fifteen (46.87%) of
      the 32 ears using the AC method, whereas all (100%) displayed positive
      elicitability of VEMP by BC method. Normal VEMP responses in both stimuli were
      evoked in all patients with sensorineural hearing loss. In patients with
      unilateral vestibular schwannomas (VS), 2 (50.00%) had neither AC-VEMP nor BC
      VEMP. CONCLUSION: Auditory stimuli delivered by bone conduction can evoke VEMP
      response. These responses are of vestibular origin and can be used in vestibular
      evaluation of patients with conductive hearing loss.

PMID- 24303435
TI  - Endoscopic cauterization of the sphenopalatine artery to control severe and
      recurrent posterior epistaxis.
AB  - INTRODUCTION: Epistaxis is one of the most common medical emergencies, making the
      management of posterior epistaxis a challenging problem for the ear, nose, and
      throat (ENT) surgeon. In the cases of conservative management failure, ligation
      of the major arteries or percutaneous embolization of the maxillary artery is
      performed routinely in most units, but rates of failure and complications are
      high. The objective of this study was to assess the effectiveness of endoscopic
      sphenopalatine artery (SPA) cauterization in patients with refractory posterior
      epistaxis. MATERIALS AND METHODS: Between April 2011 and January 2012, 27
      patients (15 males and 12 females) with refractory posterior epistaxis underwent
      endoscopic SPA cauterization in two tertiary referral hospitals in Shiraz. Three
      patients underwent bilateral cauterization. RESULTS: Four patients (from 30
      arteries) had new epistaxis after surgery, three experienced subsequent epistaxis
      requiring medical treatment, and one patient had a minor epistaxis not needing
      treatment. CONCLUSION: The SPA electrocoagulation technique seems to be safe,
      simple, fast, and effective with low rates of morbidity and complications for the
      management of refractory posterior epistaxis. Endoscopic SPA cauterization should
      be considered as an immediate second-line management when conservative treatment
      as first-line management fails.

PMID- 24303436
TI  - Middle ear exploration results in suspected otosclerosis cases: are ossicular and
      footplate area anomalies rare?
AB  - INTRODUCTION: Otosclerosis is a disease of bony labyrinth. Structural changes in
      the labyrinth often cause ossicular fixation, and thus conductive hearing loss.
      The purpose of this study was to evaluate middle ear exploration findings and
      frequency of ossicular and footplate area anomalies in patients with suspected
      otosclerosis referred to Amiralmomenin and Golsar Hospitals in Rasht, Iran.
      MATERIALS AND METHODS: In 47 patients undergone middle ear exploration in
      Amiralmomenin and Golsar hospitals from April 2001 to March 2011, the
      intraoperative findings, and other data were extracted from the medical records
      of the patients. The data was analyzed using SPSS 17 software. RESULTS: Frequency
      of fixation of stapes, malleus, and incus by age and sex in patients undergoing
      middle ear exploration showed that stapes had been fixed in 39 patients, malleus
      in 6 patients, and incus in 21 patients. Analysis of data showed that there was
      no significant association between sex and age with fixation of any of ossicles
      (P>0/05). Middle ear anomalies were seen in 16 cases (34.0%). Overhanging of
      facial nerve in 4 cases, thick stapedial crura in 5 cases, and perilymph gusher
      in 2 cases were the most frequent anomalies. CONCLUSION: This study show that the
      results of middle ear explorations in our patients in the north of Iran is
      somehow different from the typical otosclerotic cases, although the frequency of
      ossicular anomalies is better to be evaluated and compared in different areas of
      Iran, and other countries.

PMID- 24303437
TI  - Early Detection of Serum Levels of HER-2 in Patients with Head and Neck Squamous
      Cell Carcinoma.
AB  - INTRODUCTION: The presence of HER-2 has been shown to be a prognostic factor in
      many kinds of cancers, but its role in head and neck squamous cell carcinoma
      (HNSCC) is not still defined. The purpose of the current study is to investigate
      the role of HER-2 in HNSCC and its correlation with various clinicopathologic
      parameters. MATERIALS AND METHODS: Peripheral blood samples were obtained from 17
      healthy volunteers and 69 patients with HNSCC before curative surgery. The HER-2
      level was determined in each sample sandwich by ELISA. Statistical analysis was
      performed using an independent t-test, one-way ANOVA, and the Duncan procedure.
      RESULTS: Mean HER-2 serum levels were higher in patients with HNSCC compared with
      healthy controls, although the difference was not statistically significant
      (3.85ng/ml vs. 3.75ng/ml; P>0.05). The mean serum level of HER-2 in patients with
      was higher in patients with lymph node involvement, metastasis, invasion, tumor
      size >=2 cm, and stage>1, although the differences were not statistically
      significant (P>0.05). DISCUSSION: Mean HER-2 serum levels in patients with tumor
      size T3 and higher were higher than those from patients in stage T1 and T2.over
      expression of these receptor translate into disease progression, growth and
      invasiveness, with the increase serum HER-2 levels in such patients offering some
      support for this theory. CONCLUSION: In this study the mean HER-2 serum level in
      patients with HNSCC was found to be greater in comparison with the healthy
      control group, although the difference was statistically insignificant. From the
      analysis of the results of the current study we have come to the conclusion that
      by increasing sample size the rising of the serum HER-2 level in patients with
      HNSCC can be meaningful. Apart from this, the role of HER-2 as a tumor marker in
      patients with HNSCC is still controversial and needs further studies to clarify
      the significance of this biomarker for early detection or screening for HNSCC.

PMID- 24303438
TI  - Auditory Memory deficit in Elderly People with Hearing Loss.
AB  - INTRODUCTION: Hearing loss is one of the most common problems in elderly people.
      Functional side effects of hearing loss are various. Due to the fact that hearing
      loss is the common impairment in elderly people; the importance of its possible
      effects on auditory memory is undeniable. This study aims to focus on the hearing
      loss effects on auditory memory. MATERIALS AND METHODS: Dichotic Auditory Memory
      Test (DVMT) was performed on 47 elderly people, aged 60 to 80; that were divided
      in two groups, the first group consisted of elderly people with hearing range of
      24 normal and the second one consisted of 23 elderly people with bilateral
      symmetrical ranged from mild to moderate Sensorineural hearing loss in the high
      frequency due to aging in both genders. RESULTS: Significant difference was
      observed in DVMT between elderly people with normal hearing and those with
      hearing loss (P<0.22). According to the correlation test between Pure Tone
      Average (PTA) and the mean score of DVMT, increasing PTA resulted in reduction of
      DVMT score and this result was seen in both genders and all of the studied
      subjects. CONCLUSION: Apart from aging, age-related hearing loss has shown
      significant effect on auditory verbal memory. This result depicts the importance
      of auditory intervention to make better communicational skills and therefore
      auditory memory in this population.

PMID- 24303439
TI  - Ectopic supernumerary tooth in nasal septum: a case study.
AB  - INTRODUCTION: Nasal teeth eruption is a rare phenomenon. The variability of
      symptoms and generic history makes the diagnosis difficult. This difficulty is
      more challenging when the tooth is placed in the depth of septum. CASE REPORT:
      Our case is an example of this problem. Herein, we present a case of intraseptal
      tooth with nasal obstruction and septal deviation and recurrent sinusitis. We
      present preoperative imaging. CONCLUSION: Great suspicion may helpful for
      preoperative diagnosis and good deciding.

PMID- 24303440
TI  - Ectopic molar with maxillary sinus drainage obstruction and oroantral fistula.
AB  - INTRODUCTION: Ectopic tooth eruption may result owing to one of 3 processes:
      developmentalDisturbance, iatrogenic activity, or pathologic process, such as a
      tumor or a cyst. In rare cases, occlusion of the sinus ostia may predispose a
      patient to develop a maxillary sinus mucocele. When the maxillary sinus is
      invaded, symptoms usually occur late in the process. CASE REPORT: A 17 years old
      boy referred to department of Otolaryngology, Head and Neck Surgery of university
      of medical sciences, Tabriz_Iran in 2010 with chronic recurrent mucoprulent
      discharge from retromollar trigone , posterior to right superior alveolar ridge.
      CT scan revealed a dense mass resembling tooth, obstructing sinus ostium with
      homogenous opacity with ring enhancement, occupying whole sinus and expanding all
      walls. A Caldwell Luke approach in combination with endoscopy was selected.
      CONCLUSION: In the present patient, removal of ectopic tooth resolved the
      symptoms completely, the fistula obstructed and discharges discontinued. An
      ectopic tooth is a rare entity obstructing sinus ostium. The etiology of ectopic
      eruption has not yet been completely clarified, but many theories have been
      suggested,including trauma, infection, developmental anomalies and pathologic
      conditions, such as dentigerous cysts. In summary, although the ectopic teeth is
      rare but it would be assumed in presence of unilateral symptoms of sinonasal
      cavity. Therefore in peristant unilateral sinonasal symptoms we should complete
      examining of this site to rule out rare causes of these symptoms.

PMID- 24303441
TI  - Auditory-Verbal Music Play Therapy: An Integrated Approach (AVMPT).
AB  - INTRODUCTION: Hearing loss occurs when there is a problem with one or more parts
      of the ear or ears and causes children to have a delay in the language-learning
      process. Hearing loss affects children's lives and their development. Several
      approaches have been developed over recent decades to help hearing-impaired
      children develop language skills. Auditory-verbal therapy (AVT) is one such
      approach. Recently, researchers have found that music and play have a
      considerable effect on the communication skills of children, leading to the
      development of music therapy (MT) and play therapy (PT). There have been several
      studies which focus on the impact of music on hearing-impaired children. The aim
      of this article is to review studies conducted in AVT, MT, and PT and their
      efficacy in hearing-impaired children. Furthermore, the authors aim to introduce
      an integrated approach of AVT, MT, and PT which facilitates language and
      communication skills in hearing-impaired children. MATERIALS AND METHODS: In this
      article we review studies of AVT, MT, and PT and their impact on hearing-impaired
      children. To achieve this goal, we searched databases and journals including
      Elsevier, Chor Teach, and Military Psychology, for example. We also used reliable
      websites such as American Choral Directors Association and Joint Committee on
      Infant Hearing websites. The websites were reviewed and key words in this article
      used to find appropriate references. Those articles which are related to ours in
      content were selected. CONCLUSION: VT, MT, and PT enhance children's
      communication and language skills from an early age. Each method has a meaningful
      impact on hearing loss, so by integrating them we have a comprehensive method in
      order to facilitate communication and language learning. To achieve this goal,
      the article offers methods and techniques to perform AVT and MT integrated with
      PT leading to an approach which offers all advantages of these three types of
      therapy.

PMID- 24303442
TI  - The effect of local injection of epinephrine and bupivacaine on post
      tonsillectomy pain and bleeding.
AB  - INTRODUCTION: Tonsillectomy is one of the most common surgeries in the world and
      the most common problem is post-tonsillectomy pain and bleeding. The relief of
      postoperative pain helps increase early food intake and prevent secondary
      dehydration. One method for relieving pain is peritonsillar injection of
      epinephrine along with an anesthetic, which has been shown to produce variable
      results in previous studies. Study Deign: Prospective case-control study.
      SETTING: A tertiary referral centers with accredited otorhinolaryngology-head &
      neck surgery and anesthesiology department. MATERIALS AND METHODS: Patients under
      15 years old, who were tonsillectomy candidates, were assigned into one of three
      groups: placebo injection, drug injection before tonsillectomy, and drug
      injection after tonsillectomy. The amount of bleeding, intensity of pain, and
      time of first post-operative food intake were evaluated during the first 18 hours
      post operation. RESULTS: The intensity of pain in the first 30 minutes after the
      operation was lower in the patients who received injections, but the difference
      was not significant during the first 18 hours. The intensity of pain on
      swallowing during the first 6 hours was also lower in the intervention groups as
      compared with the placebo group. The amount of bleeding during the first 30
      minutes post operation was lower in the two groups who received injections, but
      after 30 minutes there was no difference. CONCLUSION: Injection of epinephrine
      and bupivacaine pre- or post- tonsillectomy is effective in reducing pain and
      bleeding. The treatment also decreases swallowing pain in the hours immediately
      after surgery.

PMID- 24303443
TI  - Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and
      IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial.
AB  - INTRODUCTION: Postoperative sore throat is a common complaint in patients with
      endotracheal intubation and has potentially dangerous complications. This
      randomized controlled trial study investigated the incidence of postoperative
      sore throat after general anesthesia when betamethasone gel is applied to a
      tracheal tube compared with when IV dexamethasone is prescribed. MATERIALS AND
      METHODS: Two hundred and twenty five American Society of Anesthesiologist (ASA)
      class I and II patients undergoing elective abdominal surgery with tracheal
      intubation were randomly divided into three groups: betamethasone gel,
      intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care
      unit, a blinded anesthesiologist interviewed all patients regarding postoperative
      sore throat at 1,6, and 24 hours after surgery. RESULTS: The incidence of sore
      throat was significantly lower in the betamethasone gel group compared with the
      IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the
      first day after surgery 10.7% of the betamethasone group had sore throat whereas
      26.7% of the IV dexamethasone group and 30.7% of the control group had sore
      throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and
      9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group,
      respectively. CONCLUSION: We concluded that wide spread application of
      betamethasone gel over tracheal tubes effectively mitigates postoperative sore
      throat, compared with IV dexamethasone application.

PMID- 24303444
TI  - Temporal processing evaluation in tinnitus patients: results on analysis of gap
      in noise and duration pattern test.
AB  - INTRODUCTION: Tinnitus is a perception of sound without external source. For
      complete assessment of tinnitus, central auditory processing abilities should be
      considered in addition to the routine psychological evaluation of tinnitus
      characteristics. Temporal processing is one of the important auditory skills that
      are necessary for complex higher level auditory processing. MATERIALS AND
      METHODS: 20 tinnitus patients and 20 healthy volunteers without tinnitus, all
      with normal auditory thresholds (<= 20 dBnHL), were enrolled in present study.
      Pure Tone Audiometry (PTA), Tinnitus evaluation, Gap in Noise (GIN) test and
      Duration Pattern Test (DPT) were applied to all participants. RESULT: Analysis of
      GIN test revealed statistically significant increases in an approximate threshold
      value of gap detection in the patients group, both in right and left sides
      (P=0.007 and P=0.011, respectively). Comparison of percentage of correct
      responses in between two groups was also statistically meaningful in right and
      left ears (P=0.019 and P=0.026, respectively). The comparison of different
      parameters of DPT in two study groups revealed no significant differences in
      percentage of correct responses between two groups (P>0.05). CONCLUSION: GIN test
      results identified auditory temporal resolution difficulties in patients with
      tinnitus, meaning that in spite of normal auditory thresholds there may be some
      possibility of abnormality in central auditory processing functions.

PMID- 24303445
TI  - Auditory temporal processing abilities in early azari-persian bilinguals.
AB  - INTRODUCTION: Auditory temporal resolution and auditory temporal ordering are two
      major components of the auditory temporal processing abilities that contribute to
      speech perception and language development. Auditory temporal resolution and
      auditory temporal ordering can be evaluated by gap-in-noise (GIN) and pitch
      pattern-sequence (PPS) tests, respectively. In this survey, the effect of
      bilingualism as a potential confounding factor on auditory temporal processing
      abilities was investigated in early Azari-Persian bilinguals. MATERIALS AND
      METHODS: In this cross-sectional non-interventional study, GIN and PPS tests were
      performed on 24 (12 men and 12 women) early Azari-Persian bilingual persons and
      24 (12 men and 12 women) Persian monolingual subjects in the age range of 18-30
      years, with a mean age of 24.57 years in bilingual and 24.68 years in monolingual
      subjects. Data were analyzed with t-test using SPSS software version 16. RESULTS:
      There was no statistically significant difference between mean gap threshold and
      mean percentages of the correct response of the GIN test and average percentage
      of correct responses in the PPS test between early Azari-Persian bilinguals and
      Persian monolinguals (P>=0.05). CONCLUSION: According to the findings of this
      study, bilingualism did not have notable effect on auditory temporal processing
      abilities.

PMID- 24303446
TI  - Surgical Treatment of Otosclerosis: Eight years' Experience at the Jordan
      University Hospital.
AB  - INTRODUCTION: To report the experience of the Jordan University Hospital with
      respect to the surgical treatment of otosclerosis and to compare results and
      complications with published studies. MATERIALS AND METHODS: The medical records
      of all patients who underwent stapes surgery for otosclerosis at the Jordan
      University Hospital during the period January 2003 to December 2010 were
      reviewed. RESULTS: Out of 130 patients who underwent stapes surgery, 104 (80%)
      fulfilled the criteria and were enrolled in this study. There were 68 (65.4%)
      females and 36 (34.6%) males (female-to-male ratio, 1.9: 1). The disease was
      bilateral in 86 (82.7%) patients. Family history for otosclerosis was positive in
      37(35.6%) patients. Tinnitus was observed at presentation in 82 (78.8%) patients
      and spontaneously resolved or improved in 51(62.2%) patients after surgery. Air
      bone gap after surgery was <= 10 dB in 79 (76.0%) patients, between 10 and 20 dB
      in 10 (9.6%) patients, and between 20 and 30 dB in four (3.8%) patients.
      Complications occurred in 17(16.3%) patients, which included: one (1.0%) deaf
      ear, two (2.0%) sensorineural hearing loss, two (2.0%) facial nerve palsy, six
      (5.8%) vertigo lasting more than 7 days, three (2.9%) chorda tympani damage, one
      (1.0%) floating of footplate, and two (2.0%) perforation of the tympanic
      membrane. CONCLUSION: The results of this study are comparable with those
      reported in the literature by surgeons with the same level of experience, but
      below than those with large series experience. Therefore, we believe that an
      experienced general ear, nose, and throat (ENT) surgeon can perform stapes
      surgery safely and successfully in the absence of an otologist.

PMID- 24303447
TI  - Which has a Greater Influence on Smile Esthetics Perception: Teeth or Lips?
AB  - INTRODUCTION: The aim of this study was to evaluate the role of teeth and lips in
      the perception of smile esthetics. MATERIALS AND METHODS: Thirty women, ranging
      between 20 and 30 years of age, all with Class I canine and molar relationships
      and no history of orthodontic treatment, were chosen. Five black and white
      photographs were taken of each participant in a natural head position while
      smiling. The most natural photo, demonstrating a social smile, was selected. Two
      other photographs were also taken from a dental frontal view of each subject
      using a retractor, as well as a lip-together smile. Three groups of judges
      including 20 orthodontists, 20 restorative specialists, and 20 laypersons were
      selected. The judges were then asked to confirm the esthetics of each picture on
      a visual analogue scale. An analysis of variance (ANOVA) and the Pearson
      correlation test were used for statistical analysis. RESULTS: For the
      orthodontists group, correlation between the scores given to the full smile and
      each of its components was significant (alpha=0.05), with equal correlation of
      each component with the full smile. In contrast to laypersons, the correlation
      between the scores given to the full smile and each of its components among
      restorative specialists was significant. CONCLUSION: For orthodontists and
      restorative specialists, esthetic details and the components of the smile (teeth
      and perioral soft tissues) were important in esthetics perception. In contrast,
      laypersons perceived no effect of esthetics detail or smile components.

PMID- 24303448
TI  - Giant keratocystic odontogenic tumor: three cases and literature review.
AB  - INTRODUCTION: A keratocystic odontogenic tumor is a benign intra-bone mass
      originating from dental lamina or its residue. It represents 2-11% of jaw cysts,
      and has a slow but aggressive growth. The evaluation of molecular
      characteristics, immunohistochemistry, and genetic expression currently have no
      established classification regarding the evolution and pathophysiologic pattern
      of these lesions. CASE REPORT: This is a clinical retrospective study with a full
      analysis of patient history regarding physical evaluation, radiologic images,
      pathology results, and surgical resection. We performed a major literature review
      concerning current concepts relating to its biological characterization. Three
      cases of keratocystic odontogenic tumor were identified. Two of the cases were
      large, with aggressive behavior and significant bone destruction and recurrence,
      which had been overlooked for more than a decade. The third case had an early
      diagnosis, and the treatment led to full recovery and complete healing.
      CONCLUSION: The keratocystic odontogenic tumor is a benign lesion with slow
      growth, which lends itself to a more conservative treatment, even in cases of
      large lesions. A better understanding of these tumors, both at the biological and
      molecular level, could lead to guidelines for treatment and prognosis of such
      patients.

PMID- 24303449
TI  - Laryngeal leiomyosarcoma, a case report and review of articles.
AB  - INTRODUCTION: Laryngeal leiomysarcoma is an extremely rare malignancy originating
      from smooth muscle cells. Its rarity is due to the fact that only less than 50
      cases of pure laryngeal leiomyosarcoma and less than 10 cases of hypopharyngeal
      leiomyosarcaoma have been reported in modern medical literature. Even though the
      clinical presentation mimics that of a laryngeal carcinoma forming the major bulk
      of the laryngeal malignancies, the difference in management, warrants an accurate
      diagnosis. CASE REPORT: We reported a case of this very rare malignancy
      presenting in the supraglottic region by highlighting the clinical features,
      histological and radiological diagnosis and management of this extremely rare
      malignant entity. CONCLUSION: An accurate histological diagnosis may be
      difficult; but supplementing by electron microscopy and immunohistochemical
      staining, the diagnosis can be reached certainly.

PMID- 24303450
TI  - A bilateral tessier number 4 and 5 facial cleft and surgical strategy: a case
      report.
AB  - INTRODUCTION: Tessier facial cleft is among the rarest facial clefts reported in
      literatures and there are many issues arguing about its multidisciplinary
      repairing techniques. Tessier number 4 and 5 are extremely rare facial anomalies.
      There are few literatures describing these clefts and their surgical modalities.
      Number 5 Tessier cleft begins medial to oral commissure in the upper lip and
      extends superiorly as a groove through the cheek and ends at the middle third of
      lower eyelid. Bonny involvement consists of alveolar ridge, maxillary bone
      lateral to infra orbital foramen and orbits lower rim and floor. Number 4 Tessier
      facial cleft begins between cupid bow and oral commissure; skirting the nose and
      pass through cheek and lateral to lacrimal duct. Bonny involvement consists of
      alveolar ridge, maxillary bone medial to infra orbital foramen and orbital rim
      and floor. CASE REPORT: This paper represents a patient with bilateral number 4
      and 5 Tessier cleft lip with unilateral complete cleft palate and surgical
      approach on her. CONCLUSION: We recommended early repair using autogenously
      tissues and minimal discarding healthy tissues as possible.

PMID- 24303451
TI  - Bilateral schwartze sign, decision-making for surgery.

PMID- 24303452
TI  - What is the purpose of launching the World Journal of Clinical Cases?
AB  - The first issue of the World Journal of Clinical Cases (WJCC), whose preparatory
      work was initiated on October 26, 2012, will be published on April 16, 2013. The
      WJCC Editorial Board has now been established and consists of 520 distinguished
      experts from 55 countries. Our purpose of launching WJCC is to publish peer
      reviewed, high-quality articles via an open-access online publishing model,
      thereby acting as a platform for communication between peers and the wider
      public, and maximizing the benefits to editorial board members, authors and
      readers. 

PMID- 24303453
TI  - Current concepts on spinal arthrodesis in degenerative disorders of the lumbar
      spine.
AB  - Back pain is a common chronic disorder that represents a large burden for the
      health care system. There is a broad spectrum of available treatment options for
      patients suffering from chronic lower back pain in the setting of degenerative
      disorders of the lumbar spine, including both conservative and operative
      approaches. Lumbar arthrodesis techniques can be divided into sub-categories
      based on the part of the vertebral column that is addressed (anterior vs
      posterior). Furthermore, one has to differentiate between approaches aiming at a
      solid fusion in contrast to motion-sparing techniques with the proposed advantage
      of a reduced risk of developing adjacent disc disease. However, the field of
      application and long-term outcomes of these novel motion-preserving surgical
      techniques, including facet arthroplasty, nucleus replacement, and lumbar disc
      arthroplasty, need to be more precisely evaluated in long-term prospective
      studies. Innovative surgical treatment strategies involving minimally invasive
      techniques, such as lateral lumbar interbody fusion or transforaminal lumbar
      interbody fusion, as well as percutaneous implantation of transpedicular or
      transfacet screws, have been established with the reported advantages of reduced
      tissue invasiveness, decreased collateral damage, reduced blood loss, and
      decreased risk of infection. The aim of this study was to review well-established
      procedures for lumbar spinal fusion with the main focus on current concepts on
      spinal arthrodesis and motion-sparing techniques in degenerative disorders of the
      lumbar spine. 

PMID- 24303454
TI  - Proteinuria in paediatric patients with human immunodeficiency virus infection.
AB  - In human immunodeficiency virus (HIV)-infected people kidney disease is as an
      important cause of morbidity and mortality. Clinical features of kidney damage in
      HIV-infected patients range from asymptomatic microalbuminuria to nephrotic
      syndrome. The lack of specific clinical features despite the presence of heavy
      proteinuria may mask the renal involvement. Indeed, it is important in HIV
      patients to monitor renal function to early discover a possible kidney injury.
      After the introduction of antiretroviral therapy, mortality and morbidity
      associated to HIV-infection have shown a substantial reduction, although a
      variety of side effects for long-term use of highly active antiretroviral
      therapy, including renal toxicity, has emerged. Among more than 20 currently
      available antiretroviral agents, many of them can occasionally cause reversible
      or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e.,
      indinavir, atazanavir and tenofovir disoproxil fumarate have a well established
      association with direct nephrotoxicity. This review focuses on major causes of
      proteinuria and other pathological findings related to kidney disease in HIV
      infected children and adolescents. 

PMID- 24303455
TI  - Endoscopic papillary balloon dilation for difficult common bile duct stones: Our
      experience.
AB  - AIM: To evaluate the efficacy and safety of endoscopic balloon dilation (EBD)
      performed for common bile duct (CBD) stones. METHODS: From a computer database,
      we retrospectively analyzed the data relating to EBD performed in patients at the
      gastrointestinal unit of the Sandro Pertini Hospital of Rome (small center with
      low case volume) who underwent endoscopic retrograde cholangiopancreatography
      (ERCP) for CBD from January 1, 2010 to February 29, 2012. All patients had a
      proven diagnosis of CBD stones studied with echography, RMN-cholangiography and,
      when necessary, with computed tomography of the abdomen (for example, in cases
      with pace-makers). Prophylactic therapies, with gabexate mesilate 24 h before the
      procedure and with an antibiotic (ceftriaxone 2 g) 1 h before, were administered
      in all patients. The duodenum was intubated with a side-viewing endoscope under
      deep sedation with intravenous midazolam and propofol. The patients were placed
      in the supine position in almost all cases. EBD of the ampulla was performed
      under endoscopic and fluoroscopic guidance with a balloon through the scope
      (Hercules, wireguided balloon((r)), Cook Ireland Ltd. and CRE((r)), Microvasive,
      Boston Scientific Co., Natick, MA, United States). RESULTS: A total of 14
      patients (9 female, 5 male; mean age of 73 years; range 57-82 years) were
      enrolled in the study, in whom a total of 15 EBDs were performed. All patients
      underwent minor endoscopic sphincterotomy (ES) prior to the EBD. The size of
      balloon insufflation depended on stone size and CBD dilation and this was
      performed until it reached 16 mm in diameter. EBD was performed under endoscopic
      and fluoroscopic guidance. The balloon was gradually filled with diluted contrast
      agent and was maintained inflated in position for 45 to 60 s before deflation and
      removal. The need for precutting the major papilla was 21.4%. In one patient (an
      81-year-old), EBD was performed in a Billroth II. Periampullary diverticula were
      found only in a 74-year-old female. The adverse event related to the procedures
      (ERCP + ES) was only an intra procedural bleeding (6.6%) that occurred after ES
      and was treated immediately with adrenaline sclerotherapy. No postoperative
      complications were reported. CONCLUSION: With the current endoscopic techniques,
      very few patients with choledocholithiasis require surgery. EBD is an efficacious
      and safe procedure.

PMID- 24303456
TI  - Gastric hyperplastic polyps causing upper gastrointestinal hemorrhage in a young
      adult.
AB  - Here, we report a case of a young man who presented with a significant upper
      gastrointestinal bleed treated by endoscopic removal of multiple hyperplastic
      polyps. Gastric hyperplastic polyps are a relatively uncommon cause of overt
      gastrointestinal bleeding. While most hyperplastic gastric polyps are
      asymptomatic, they may present with abdominal pain, iron deficiency anemia or
      gastric outlet obstruction. These polyps are associated with conditions such as
      Helicobacter pylori gastritis and atrophic autoimmune gastritis, which predispose
      the epithelium to chronic inflammation and epithelial repair. The patient
      presented to Northwestern Memorial Hospital in July 2011. The polyps were
      resected by clip-assisted snare polypectomy. Histopathologic assessment of the
      resected polyps demonstrated multiple, non-ulcerative hyperplastic polyps
      measuring 1.3-1.8 cm in size, without evidence of dysplasia or malignancy. This
      case describes a young adult patient with multiple, large gastric polyps causing
      overt gastrointestinal bleeding. This is a rare presentation in a young
      individual, as these polyps are typically identified in patients older than 60
      years of age and less commonly, pediatric populations. 

PMID- 24303457
TI  - Saphenous graft on transesophageal echocardiogram masquerading as an abnormal
      vascular communication into the right atrium.
AB  - An unknown aberrant flow in the right atrium observed on doppler with
      transesophageal echocardiogram (TEE) in a patient with prior coronary bypass. TEE
      revealed normal size left ventricle with severely dilated left atrium. There was
      moderate aortic regurgitation and moderate aortic stenosis noted. Patient was
      incidentally found to have an abnormal vascular communication noted to the right
      atrium. To further evaluate this finding, the patient underwent cardiac magnetic
      resonance angiography which revealed that the tubular structure noted on TEE was
      actually a graft that was abutting onto the coronary sinus, and the flow anomaly
      was really the graft coming up and running adjacent to the coronary sinus. 

PMID- 24303458
TI  - Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenia purpura (TTP) was first described in 1924 as a
      "pathologic alteration of the microvasculature, with detachment or swelling of
      the endothelium, amorphous material in the sub-endothelial space, and luminal
      platelet aggregation leading to compromise of the microcirculation". Ticlopidine
      induced TTP has been highly associated with autoimmune induced reduction in
      ADAMTS-13 activity. These findings, to a lesser extent, have also been found in
      clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a
      patient that presented with acute stroke, renal failure, and non-ST elevation
      myocardial infarction. 

PMID- 24303459
TI  - Intracystic hemorrhage in a non-endometriotic mullerian vaginal cyst.
AB  - The commonest type of simple vaginal cyst is the Mullerian cyst. These are
      typically lined by columnar epithelium and contain serous or mucinous fluid. If
      blood is found in the cyst, the source is usually due to the presence of
      endometrial elements in the cyst wall. The cyst is then termed an endometriotic
      cyst. In this case report, we have described a woman with a symptomatic 3 cm
      upper vaginal cyst who underwent surgical excision of the cyst. The cyst cavity
      was found to be full of old dark blood and mucous, however the wall contained no
      endometrial tissue and was lined by columnar epithelium which stained positive
      for mucous with mucicarmine. No cause for the intracystic hemorrhage was
      identified. We conclude that intracystic hemorrhage can occur in a simple
      Mullerian vaginal cyst in the absence of endometrial components. 

PMID- 24303460
TI  - Hodgkin's lymphoma coexisting with liver failure secondary to acute on chronic
      hepatitis B.
AB  - Acute on chronic liver failure (ACLF) is rarely the initial manifestation of a
      malignant process or precipitated by the initiation of anti-viral treatment with
      a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally
      associated with initiation of Entecavir for treatment of chronic hepatitis B.
      Early Hodgkin's lymphoma (HL) was unmasked with initiation of the anti-viral
      treatment which may have exacerbated ACLF. To the best of our knowledge, this has
      not been described in the literature. In reviewing our patients clinical course
      and liver autopsy, he developed a severe acute exacerbation of his chronic
      hepatitis B virus coinciding with the institution of antiviral therapy and the
      underlying HL perhaps modulating the overall degree of hepatic injury. 

PMID- 24303461
TI  - Fulminant sepsis after liver biopsy: A long forgotten complication?
AB  - We report on a 74-year-old patient with recurrent cholangitis and a large
      juxtapapillary duodenal diverticulum. Despite drainage of the common bile duct by
      an endoscopically placed stent, the elevated liver enzymes normalized only
      partially. To rule out other possible causes of liver injury, a percutaneous
      liver biopsy was done. After the liver biopsy the patient developed fulminant
      septic shock and died within 24 h. We discuss the possible causes of the septic
      shock following percutaneous liver biopsy in our patient and give a concise
      overview of the literature. 

PMID- 24303462
TI  - Treatment of a patient with congenital analbuminemia with atorvastatin and
      albumin infusion.
AB  - Congenital analbuminemia is a rare autosomic recessive inherited disorder
      characterized by low plasma albumin and hypercholesterolemia, which may increase
      cardiovascular risk. Patients are essentially asymptomatic, apart from ease of
      fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for
      safely treating both hypercholesterolemia and analbuminemia in order to
      eventually decrease the atherosclerotic risk. We report a case of congenital
      analbuminemia (1.0 g/dL) in a 38-year-old male with hypercholesterolemia (range:
      406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated
      dilation (FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was
      associated with the appearance of peripheral edema. Two-months of infusion with
      albumin improved FMD (7%) and reduced serum cholesterol (273 mg/dL), supporting
      the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment,
      together with periodical albumin infusions, may contribute to the safe reduction
      of cardiovascular risk. 

PMID- 24303463
TI  - Schwannoma of the rectum: A case report and literature review.
AB  - Schwannoma is a tumor originating from the Schwann cells. Gastrointestinal
      schwannomas are uncommon stromal tumors of the intestinal tract and, in
      particular, rectal schwannomas are extremely rare. In fact, it is well
      established that schwannomas appear more frequently in the stomach and in the
      small intestine, while location in the colon or in the rectum is uncommon.
      Reading the literature, only few cases of rectal schwannoma have been reported.
      Their diagnosis is confirmed by the immunohistochemical panel (S-100 protein).
      When these tumors are located in the colon and in the rectum, radical excision
      with wide margins is mandatory, due to their tendency to recur locally or become
      malignant, if left untreated. In the present study, we describe a case of a
      rectal schwannoma occured in a 72-year-old man, presented as a small polypoid
      lesion, which was successfully removed in toto by hot-biopsy, during the same
      endoscopy, due to the dimensons. No recurrence of the lesion was observed after 6
      mo of follow-up. 

PMID- 24303464
TI  - Liver failure in an obese middle-aged woman after biliointestinal bypass.
AB  - Obesity is considered an emerging epidemic that is often associated with non
      alcoholic fatty liver disease. Among the therapeutic options for morbid obesity,
      bariatric surgery plays an important role when conventional therapies fail. The
      effects of bariatric surgery on liver function and morphology are controversial
      in the literature. Liver failure has been reported after jejunoileal bypass
      (JIB), biliopancreatic diversion and gastric bypass. Biliointestinal bypass (BIB)
      is considered an effective procedure among recently introduced bariatric surgery
      techniques. It is a clinically safe, purely malabsorptive operation in which the
      blind intestinal loop of the JIB is anastomosed to the gallbladder, allowing a
      portion of bile to transit into excluded intestinal tract. BIB is the only
      procedure, to our knowledge, to have no liver side effects reported in the
      literature. We report the case of a young obese woman who developed liver failure
      8 mo after BIB. She had a rapid weight loss (70 kg) with a reduction in body mass
      index of 41% from January to September 2012. Because of a severe hepatic
      decompensation, she was referred to a transplantation centre. We strongly believe
      that the most important pathogenetic mechanism involved in the development of
      liver injury is the rapid weight loss that produced a significant fatty liver
      infiltration. 

PMID- 24303465
TI  - Can neck swelling lead to spinal cord compression?
AB  - Spinal cord compression (SCC) caused by cervical spinal canal invasion of a
      pulmonary sarcomatoid carcinoma metastasis has never been reported previously. A
      59-year-old man, with a history of pulmonary carcinosarcoma, developed over
      several weeks important neck swelling. Admitted to our division with severe
      tetraparesis he underwent a cervical spine computed tomography scan that showed a
      large cervical mass measuring 11 cm * 27 cm * 17 cm with SCC, extending from the
      occiput to C7. Emergency spinal cord decompression was performed leading to minor
      neurological improvement. Poor outcome was due to the unusual clinical sign that
      led to late diagnosis and treatment. 

PMID- 24303466
TI  - Tumour induced osteomalacia due to a sinonasal hemangiopericytoma: A case report.
AB  - Tumour induced osteomalacia (TIO) is a rare and often unrecognized cause of
      hypophosphatemia. We report on a case of TIO due to a hemangiopericytoma
      originating from the left nasal sinus. The patient was a 55-year-old male with a
      3-year history of left hip pain and an undisplaced left hip fracture. Biochemical
      testing demonstrated low levels of serum phosphate and serum 1,25
      dihydroxyvitamin D, and an elevated level of fibroblast growth factor 23.
      Octreotide scanning demonstrated uptake in the left nasal sinus area and a
      computed tomography scan revealed a left nasal sinus mass. The patient underwent
      surgical resection of the mass and histology was consistent with a sinonasal
      hemangiopericytoma. His serum phosphate levels normalized almost immediately
      after surgery and he had complete resolution of hip pain. Our case highlights the
      importance of considering TIO when assessing patients with low serum phosphate. 

PMID- 24303467
TI  - Low grade chondrosarcoma of the nasal septum.
AB  - Chondrosarcoma of the nasal septum is extremely rare. In some cases, it may be
      difficult to preoperatively differentiate low grade chondrosarcoma from benign
      cartilaginous tumors such as chondroma. We report a case of low grade
      chondrosarcoma of the nasal septum with characteristic radiologic findings.
      Characteristic radiologic findings such as calcifications on computed tomography
      scan and a ring-and-arc pattern on enhanced T1 weighted image were useful in the
      preoperative diagnosis of low grade chondrosarcoma of the septum. Awareness of
      radiologic findings of low grade chondrosarcoma can help to make an accurate
      diagnosis and perform appropriate excision, leading to successful local control. 

PMID- 24303468
TI  - Oral rehabilitation of a Parkinson's patient: A case report.
AB  - Parkinson's disease is an idiopathic disorder of the central nervous system,
      characterized by resting tremors, muscular rigidity, slow and decreased
      movements. Oral rehabilitation of these patients requires special care,
      especially in those cases where the patient's socioeconomic status is not good
      and patient cannot come several times for fabrication of a complete denture. This
      clinical report presents a case of a Parkinson's patient who was completely
      rehabilitated in 3 appointments using special techniques. Border molding, final
      impression and jaw relation procedures were done in one appointment by using a
      custom tray with detachable handles and occlusal rims. 

PMID- 24303469
TI  - Isolated gastric Crohn's disease.
AB  - Crohn's disease (CD) is a chronic idiopathic inflammatory disease of
      gastrointestinal tract characterized by segmental and transmural involvement of
      gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and
      account for 40% of cases and involvement of small intestine in about 30%. The
      stomach is rarely the sole or predominant site of CD. To date there are only a
      few documented case reports of adults with isolated gastric CD and no reports in
      the pediatric population. Isolated stomach involvement is very unusual
      presentation accounting for less than 0.07% of all gastrointestinal CD. The
      diagnosis is difficult to establish in cases of atypical presentation as in
      isolated gastroduodenal disease. In the absence of any other source of disease
      and in the presence of nonspecific upper GI endoscopy and histological findings,
      serological testing can play a vital role in the diagnosis of atypical CD. Recent
      studies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and
      anti-Saccharomycescervisia antibody may be used as additional diagnostic tools.
      The effectiveness of infliximab in isolated gastric CD is limited to only a few
      case reports of adult patients and the long-term outcome is unknown. 

PMID- 24303470
TI  - Biological therapy for dermatological manifestations of inflammatory bowel
      disease.
AB  - Ulcerative colitis and Crohn's disease are the two forms of inflammatory bowel
      disease (IBD). The advent of biological drugs has significantly changed the
      management of these conditions. Skin manifestations are not uncommon in IBD.
      Among the reactive lesions (immune-mediated extraintestinal manifestations),
      erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous
      ills associated with IBD, while psoriasis is the dermatological comorbidity
      disease observed more often. In particular, in the last few years, anti-tumor
      necrosis factor (TNF)-alpha agents have been successfully used to treat
      psoriasis, especially these kinds of lesions that may occur during the treatment
      with biological therapies. The entity of the paradoxical manifestations has been
      relatively under reported as most lesions are limited and a causal relationship
      with the treatment is often poorly understood. The reason for this apparent side
      effect of the therapy still remains unclear. Although side effects may occur,
      their clinical benefits are undoubted. This article reviews the therapeutic
      effects of the two most widely used anti-TNF-alpha molecules, infliximab (a
      fusion protein dimer of the human TNF-alpha receptor) and adalimumab (a fully
      human monoclonal antibody to TNF-alpha), for the treatment of the major cutaneous
      manifestations associated with IBD (EN, PG and psoriasis). 

PMID- 24303471
TI  - Globalised world, globalised diseases: A case report on an amoebiasis-associated
      colon perforation.
AB  - In 2010 the World Health Organisation estimated the number of infections with
      Entamoeba histolytica at about 50 million cases including 100000 fatal courses.
      In most cases this infection is a subclinical event with few or none symptoms
      noticeable for the patient. Courses of this disease and incidence of this
      parasite in industrialised nations are not yet fully investigated. Our case
      reports about a 68-year-old male patient from Turkey who lives for more than 30
      years in Germany and had not been abroad during the past 2 years. Resistant
      asymptomatic amoebic dormant bodies caused an emergency-laparoscopy and revealed
      the seldom complication of a colon perforation. In the age of globalisation all
      providers in the health care systems are urged to acquaint themselves also with
      non-typical syndromes for the countries they work in order to reduce preventable
      morbidity respectively mortality rates. 

PMID- 24303472
TI  - A vaginal drain of a pelvic abscess due to colonic diverticulitis.
AB  - Although well recognized for tubo-ovarian abscesses, we report, in our best
      knowledge, the first case of a vaginal drain of a pelvic abscess due to colonic
      diverticulitis. A 78-year-old patient presented with abdominal and pelvic pain,
      fever (39.3  degrees C) and an elevated white blood cell count (18500/mL). After
      abdominopelvic computed tomography the patient was presumed to have a pelvic
      abscess, which developed as a complication of the sigmoid diverticulitis. Due to
      the numerous intervening structures that create obstacles to safe percutaneous
      access, we planned a trans-vaginal drain. A rapid recovery was obtained within 2
      d from the procedure and, at present, the follow-up was uneventful after 18 mo.
      We believe that transvaginal drain of pelvic abscess could be a useful
      alternative, when percutaneous approach is not feasible. 

PMID- 24303473
TI  - A rare case of acute compartment syndrome after saphenectomy.
AB  - Saphenectomy is one of the most validated criteria to treat varicose veins of the
      lower legs. Although many complications were well described, little is known
      about compartment syndrome due to muscle ischemia caused by constrictive bandages
      applied after stripping of varicose veins. We presented a case of successful
      conservative treatment of compartment syndrome after saphenectomy. Rehabilitation
      was found effective in improving fatigue, stiffness and tenderness showing the
      effectiveness of the combined conservative-rehabilitative treatment. However
      conservative treatment could not be considered the treatment of choice in daily
      practice. A severity score assessment of compartment syndrome should be useful to
      assess to which patients is allowed to not perform fasciotomy. 

PMID- 24303474
TI  - Synchronous rectal and esophageal cancer treated with chemotherapy followed by
      two-stage resection.
AB  - We report a case of 61-year-old male who had synchronous advanced rectal cancer
      involving the urinary bladder massively associated with multiple liver
      metastases, and esophageal cancer successfully treated by neoadjuvant
      chemotherapy followed by two-stage resection. Although complete resection of each
      of the lesions was considered possible by performing anterior pelvic
      exenteration, liver resection, and esophagectomy, it might be impossible for the
      patient to endure the stress of all of these operative procedures at once.
      Therefore, we planned to perform staged treatment with prioritizing
      consideration. First, we instituted chemotherapy with the FOLFOX (oxaliplatin +
      fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control
      both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior
      resection combined with cystoprostatectomy and lateral segmentectomy plus partial
      hepatectomy was performed followed by staged esophagectomy with three-field lymph
      node dissection. It was possible to use oxaliplatin and cetuximab safely as
      neoadjuvant therapy not only for advanced rectal cancer but for esophageal
      cancer, and it was effective. 

PMID- 24303475
TI  - Squamous papilloma in the external auditory canal: A common lesion in an uncommon
      site.
AB  - Squamous papillomas (SPs) are common benign neoplastic lesions, usually affecting
      the skin, oral mucosa, upper aerodigestive tract and genital organs. However, SPs
      of the external auditory canal (EAC) are rarely reported in the English
      literature. In this report, we present a 19-year-old female with left EAC SP. The
      etiology, natural course, diagnosis and management of this disease are discussed,
      with a brief review of the literature. 

PMID- 24303477
TI  - Hepatitis C treatment with triple therapy in a patient with hemophilia A.
AB  - We report a case of successful treatment of chronic hepatitis C infection with
      telaprevir-based triple therapy in a patient with hemophilia A complicated by
      factor VIII inhibitor. A twenty-two years old male with hereditary hemophilia A
      and high-titer factor VIII inhibitor was taking maintenance doses of recombinant
      factor VIII. He visited our clinic for treatment of his chronic hepatitis C with
      the newly instituted protease inhibitor based therapy. He was diagnosed with
      hepatitis C genotype 1a at one year of age. He was initiated on telaprevir,
      ribavirin and peg-interferon for treatment of hepatitis C and qualified for
      response-guided therapy. He completed treatment at 24 wk with minimal adverse
      effects. Notably, after 4 wk of hepatitis C treatment, his factor VIII inhibitor
      screen was negative and the dose for recombinant factor VIII decreased by half of
      the initial dosing before he was treated for hepatitis C. We suspect that
      suppressing hepatitis C may help decrease factor VIII inhibitor level and the
      need for recombinant factor VIII. 

PMID- 24303476
TI  - Monitoring photodynamic therapy of head and neck malignancies with optical
      spectroscopies.
AB  - In recent years there has been significant developments in photosensitizers
      (PSs), light sources and light delivery systems that have allowed decreasing the
      treatment time and skin phototoxicity resulting in more frequent use of
      photodynamic therapy (PDT) in the clinical settings. Compared to standard
      treatment approaches such as chemo-radiation and surgery, PDT has much reduced
      morbidity for head and neck malignancies and is becoming an alternative treatment
      option. It can be used as an adjunct therapy to other treatment modalities
      without any additive cumulative side effects. Surface illumination can be an
      option for pre-malignant and early-stage malignancies while interstitial
      treatment is for debulking of thick tumors in the head and neck region. PDT can
      achieve equivalent or greater efficacy in treating head and neck malignancies,
      suggesting that it may be considered as a first line therapy in the future.
      Despite progressive development, clinical PDT needs improvement in several topics
      for wider acceptance including standardization of protocols that involve the same
      administrated light and PS doses and establishing quantitative tools for PDT
      dosimetry planning and response monitoring. Quantitative measures such as optical
      parameters, PS concentration, tissue oxygenation and blood flow are essential for
      accurate PDT dosimetry as well as PDT response monitoring and assessing therapy
      outcome. Unlike conventional imaging modalities like magnetic resonance imaging,
      novel optical imaging techniques can quantify PDT-related parameters without any
      contrast agent administration and enable real-time assessment during PDT for
      providing fast feedback to clinicians. Ongoing developments in optical imaging
      offer the promise of optimization of PDT protocols with improved outcomes. 

PMID- 24303478
TI  - Paradoxical embolus straddling patent foramen ovale demonstrated by computed
      tomographic pulmonary angiography.
AB  - An elderly gentleman presented to the emergency department with a recent history
      of dyspnoea, collapse and transient neurological symptoms. He was noted to be
      hypoxic with a significantly elevated D Dimer. A computer tomography pulmonary
      angiogram demonstrated a large embolus with a further filling defects within the
      left and the right atria, abutting the inter-atrial septum. Suspicion of a
      paradoxical pulmonary embolus was raised and the patient subsequently underwent
      echocardiography which confirmed a patent foramen ovale (PFO). He was commenced
      on warfarin therapy. In patients with elevated right heart pressure, a PFO can be
      unmasked and give rise to cerebral emboli. Clinical suspicion should be raised in
      patients with pulmonary emboli or deep venous thrombosis if there is a
      concomitant history of focal neurological symptoms. 

PMID- 24303479
TI  - Syringomyelia associated with cervical spondylosis: A rare condition.
AB  - Spinal spondylosis is an extremely common condition that has only rarely been
      described as a cause of syringomyelia. We describe a case of syringomyelia
      associated with cervical spondylosis admitted at our division and treated by our
      institute. It is the case of a 66-year-old woman. At our observation she was
      affected by moderate-severe spastic tetraparesis. T2-weighted magnetic resonance
      imaging (MRI) showed an hyperintense signal within spinal cord from C3 to T1 with
      a more sharply defined process in the inferior cervical spinal cord. At the same
      level bulging discs, facets and ligamenta flava hypertrophy determined a
      compression towards subarachnoid space and spinal cord. Spinal cord compression
      was more evident in hyperextension rather than flexion. A 4-level laminectomy and
      subsequent posterior stabilization with intra-articular screws was executed. At 3
      mo follow up there was a regression of tetraparesis but motor deficits of the
      lower limbs residuated. At the same follow up postoperative MRI was executed. It
      suggested enlargement of the syrinx. Perhaps hyperintensity within spinal cord
      appeared "bounded" from C3 to C7 with clearer margins. At the level of surgical
      decompression, subarachnoid space and spinal cord enlargement were also evident.
      A review of the literature was executed using PubMed database. The objective of
      the research was to find an etiopathological theory able to relate syringomyelia
      with cervical spondylosis. Only 6 articles have been found. At the origin of
      syringomyelia the mechanisms of compression and instability are proposed. Perhaps
      other studies assert the importance of subarachnoid space regard cerebrospinal
      fluid (CSF) dynamic. We postulate that cervical spine instability may be the
      cause of multiple microtrauma towards spinal cord and consequently may damage
      spinal cord parenchyma generating myelomalacia and consequently syrinx. Otherwise
      the hemorrhage within spinal cord central canal can cause an obstruction of CSF
      outflow, finally generating the syrinx. On the other hand in cervical spondylosis
      the stenotic elements can affect subarachnoid space. These elements rubbing
      towards spinal cord during movements of the neck can generate arachnoiditis,
      subarachnoid hemorrhages and arachnoid adhesions. Analyzing the literature these
      "complications" of cervical spondylosis are described at the origin of
      syringomyelia. So surgical decompression, enlarging medullary canal prevents
      rubbings and contacts between the bone-ligament structures of the spine towards
      spinal cord and subarachnoid space therefore syringomyelia. Perhaps stabilization
      is also necessary to prevent instability of the cervical spine at the base of
      central cord syndrome or syringomyelia. Finally although patients affected by
      central cord syndrome are usually managed conservatively we advocate, also for
      them, surgical treatment in cases affected by advanced state of the symptoms and
      MRI. 

PMID- 24303480
TI  - Trans-sacral screw fixation in the treatment of high dyplastic developmental
      spondylolisthesis.
AB  - We describe the case of a 67-year-old woman with L5-S1 ontogenetic
      spondylolisthesis treated with pedicle fixation associated with interbody
      arthrodesis performed with S1-L5 trans-sacral screwing according to the technique
      of Bartolozzi. The procedure was followed by a wide decompressive laminectomy.
      The patient had a progressive improvement of the symptoms which gradually
      disappeared in 12 mo. The radiograph at 6 and 12 mo showed complete fusion
      system. The choice of treatment in L5-S1 ontogenetic spondylolithesis is related
      to a correct clinical and diagnostic planning (X-ray, computer tomography
      magnetic resonance imaging, Measurement). In particular, the severity index and
      the square of unstable zone, and the standard measurements already described in
      the literature, are important to understand and to plane the correct surgical
      strategy, that require, in most of the times, fusion and interbody artrodesis. 

PMID- 24303481
TI  - Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy
      for renal cell carcinoma.
AB  - We report the case of a left laparoscopic nephroureterectomy with the incidental
      discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal
      hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man.
      Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non
      Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma
      discovery. There are no signs of relapse after two years of follow up.
      Coexistence in the same patient is an extremely rare condition. We review the
      literature about this issue to clarify this association. 

PMID- 24303482
TI  - Colonic lipoma covered by hyperplastic epithelium: Case report.
AB  - Colonic lipomas are submucosal nonepithelial tumors covered by intact or eroded
      mucosa. In rare cases, alterations in the mucosa covering a lipoma include
      hyperplasia, adenoma, atrophy, ulceration, and necrosis. Here, we report a case
      of a colonic lipoma covered by hyperplastic epithelium in a 68-year-old woman.
      Based on the colonoscopy findings, a snare polypectomy was performed for a
      presumptive diagnosis of an epithelial lesion; however, the histological
      examination revealed a colonic submucosal lipoma with overlying hyperplastic
      epithelium. 

PMID- 24303483
TI  - Peripheral cemento-ossifying fibroma: A case report with review of literature.
AB  - Peripheral cemento-ossifying fibroma (PCOF) is a rare osteogenic neoplasm that
      ordinarily presents as an epulis-like growth. This is of a reactive rather than
      neoplastic nature and its pathogenesis is uncertain. PCOF predominantly affects
      adolescent and young adults with greatest prevalence around 28 years. We report
      here a rare clinical case of PCOF of the mandible, 1 cm mesiodistally and 1.5 cm
      occluso-gingivally in diameter, which caused difficulty in eating and speech, in
      a 42-year-old female patient. She was asymptomatic for 1 year and on follow-up
      for 6 mo post surgically showed gingival health and normal radioopacity of bone
      without any recurrence. Clinical, radiographic and histological characteristics
      are discussed and recommendations regarding differential diagnosis, treatment and
      follow up are provided. The controversial varied nomenclature and possible
      etiopathogenesis of PCOF are emphasized. 

PMID- 24303485
TI  - Zinc: Role in the management of diarrhea and cholera.
AB  - Diarrhea and cholera are major health problems. Vibrio cholera, the causative
      agent of cholera, infects the small intestine, resulting in vomiting, massive
      watery diarrhea and dehydration. Reduced water and electrolyte absorption is also
      due to zinc deficiency. Zinc has an important role in recovery from the disease.
      The combination of zinc with cholera vaccine and oral rehydration solutions has a
      positive impact on cholera and diarrhea. It has led to a decrease in the
      mortality and morbidity associated with diarrhea. 

PMID- 24303484
TI  - Elastic resistance of the spine: Why does motion preservation surgery almost
      fail?
AB  - Single metamere motility should not be interpreted merely as a movement on the 3
      planes but also, and above all, as elastic resistance to dynamic stress on these
      3 planes. In the light of this consideration, the aim of motion preservation is
      to neutralize excessive movements while preserving the physiological
      biomechanical properties of the metamere involved to interrupt the progression of
      degenerative processes and to prevent adjacent segment disease. Despite the fact
      that a myriad of devices have been developed with the purpose of achieving
      dynamic neutralization of the spine, there are now some doubts regarding the true
      efficacy of these devices. 

PMID- 24303486
TI  - Giant hibernoma of the thoracic pleura and chest wall.
AB  - Hibernoma is a rare tumor containing prominent brown adipocytes that resemble
      normal brown fat. Brown fat (versus white fat) is predominantly found in
      hibernating mammals and infants. Brown fat adipocytes contain a higher number of
      small lipid droplets and a much denser concentration of mitochondria. The tumor
      can occur in a variety of locations however the extremities, followed by the head
      and neck, have been the most common sights. All variants of hibernoma described
      have followed a benign course with the majority presenting as a small, lobulated,
      nontender lesions. We present a case of a giant hibernoma arising from the pleura
      which invaded the intra and extra-thoracic chest. 

PMID- 24303487
TI  - Noncoronary sinus of Valsalva rupture into the right atrium with a coexisting
      perimembranous ventricular septal defect.
AB  - Ruptured sinus of Valsalva is very uncommon, and is < 1% of all congenital
      defects. The incidence ranges from 0.1%-3.5%. There is a male to female
      predominance of 4:1, with the highest incidence in the Asian population. Higher
      incidence is also seen in patients with Marfan's syndrome and Ehlers Danlos
      syndrome. There is a higher association of ruptured sinus of Valsalva with
      ventricular septal defect (VSD), aortic stenosis, and bicuspid valve defect.
      While most patients with VSD often have rupture of their right coronary sinus of
      Valsalva into the right ventricle due to poor structural integrity, we present a
      rare case of a patient with VSD who had rupture of his noncoronary sinus of
      Valsalva into the right atrium. 

PMID- 24303488
TI  - Vulvar granular cell tumor.
AB  - Granular cell tumors are rare, usually benign, soft tissue neoplasms of neural
      origin. They occur more often in females than males, the peak age incidence is in
      the fourth through fifth decades. They can occur anywhere in the body with up to
      15% situated in the vulva. The commonest presentation is as an asymptomatic mass.
      Microscopic findings are usually sufficient, but immunohistochemistry can also be
      helpful in confirming the diagnosis. The vulvar tumors are benign in 98% of cases
      with 2% reported as malignant. In this case report we describe a woman with a
      granular cell tumor confirmed by biopsy who underwent excision of the mass but
      with focal extension to the resection margin on microscopy. Our recommendation of
      re-excision was declined. Since it is not uncommon with these tumors to find
      groups of tumor cells extending beyond the macroscopic limits of growth, we
      conclude that it is advisable to have margins assessed intraoperatively by frozen
      section such that further excision can be performed for positive margins. Our
      patient has been followed for 18 mo without recurrence, should the tumor recur,
      re-excision, with frozen section control, is indicated. Recurrence rates are
      reported as 2%-8% with clear margins and 20% with positive margins. 

PMID- 24303489
TI  - Rare case of a solitary huge hepatic cystic lymphangioma.
AB  - A hepatic lymphangioma is a rare benign neoplasm and is usually associated with
      lymphangiomas of other viscera. A hepatic lymphangioma can be solitary, cystic or
      associated with multiple liver lesions and is characterized by cystic dilatation
      of lymphatic vessels in the hepatic parenchyma. A solitary lymphangioma is
      unusual. Here we report a rare case of a solitary huge primary hepatic cystic
      lymphangioma in a 42-year-old woman. It was discovered on routine physical
      examination and the patient had no obvious symptoms. Ultrasonography and computed
      tomography (CT) showed a giant "hepatic neoplasm" that occupied the right liver
      lobe. The lesion was approximately 20.0 cm * 15.0 cm * 10.0 cm in size and
      contained cystic and solid components. There were multiple septa inside the
      tumor, with some calcifications in the septa. Surgical resection was performed.
      Histological examination revealed multiple cystic structures lined with
      epithelial cells on the inner walls, accompanied by interstitial swelling and
      necrosis. The patient has now been followed up for nearly two years after
      surgery, with no recurrence to date. 

PMID- 24303490
TI  - Desmopression is an effective adjunct treatment for reversing excessive
      hyponatremia overcorrection.
AB  - We report a case of a 50-year-old malnourished African American male with
      hiccups, nausea and vomiting who was brought to the Emergency Department after
      repeated seizures at home. Laboratory evaluations revealed sodium (Na(+)) 107
      mmol/L, unmeasurably low potassium, chloride < 60 mmol/L, bicarbonate of 38
      mmol/L and serum osmolality 217 mOsm/kg. Seizures were controlled with 3% saline
      IV. Once nausea was controlled with iv antiemetics, he developed large volume
      free water diuresis with 6 L of dilute urine in 8 h (urine osmolality 40-60
      mOsm/kg) and serum sodium rapidly rose to 126 mmol/L in 12 h. Both intravenous
      desmopressin and 5% dextrose in water was given to achieve a concentrated urine
      and to temporarily reverse the acute rise of sodium, respectively. Serum Na(+)
      was gradually re-corrected in 2-3 mmol/L daily increments from 118 mmol/L until
      130 mmol/L. Hypokalemia was slowly corrected with resultant auto-correction of
      metabolic alkalosis. The patient discharged home with no neurologic sequaele on
      the 11(th) hospital day. In euvolemic hyponatremic patients, controlling nausea
      may contribute to unpredictable free water diuresis. The addition of an
      antidiuretic hormone analog, such as desmopressin can limit urine output and
      prevent an unpredictable rise of the serum sodium. 

PMID- 24303491
TI  - Side matters: An intriguing case of persistent left superior vena-cava.
AB  - Persistent left superior vena cava, usually an incidental finding, is the most
      common thoracic vein anatomical variation draining into the coronary sinus.
      Central venous catheter procedures may be complicated secondary to the presence
      of a persistent left superior vena cava, leading to life-threatening
      complications such as arrhythmias, cardiogenic shock, and cardiac arrest. We
      present a case of persistent superior vena cava diagnosed on transthoracic
      echocardiogram (TTE) in a patient with congestive heart failure. A dilated
      coronary sinus was identified on TTE, followed by injection of agitated saline
      into the left antecubital vein resulting in filling of the coronary sinus prior
      to the right atrium-an indication of persistent left superior vena-cava. This
      also was confirmed on cardiac computed tomography. Such a diagnosis is critical
      in patients who may undergo central venous catheter procedures such as our
      patient's potential requirement for an implantable cardiovertor defibrillator due
      to severe global left ventricular systolic dysfunction. The presence of a
      persistent left superior vena cava should always be suspected when the guidewire
      takes a left-sided downward course towards the right atrium at the level of the
      coronary sinus. Therefore, special attention should be paid to the imaging work
      up prior to central venous catheter procedures. 

PMID- 24303492
TI  - Biventricular pulsus alternans: An echocardiographic finding in patient with
      pulmonary embolism.
AB  - Pulsus alternans is characterized by regular rhythm with beat-to-beat alternation
      of systolic pressures. Left ventricular alternans is usually found in severe left
      ventricular dysfunction due to cardiomyopathy, coronary artery disease, systemic
      hypertension, and aortic stenosis. Right ventricular alternans is usually
      associated with left ventricular alternans, right ventricular dysfunction,
      pulmonary embolism, and pulmonary hypertension. Biventricular alternans is rare
      and associated with severe left ventricular dysfunction and left anterior
      descending coronary artery disease. The exact mechanism of pulsus alternans has
      not been clearly delineated, and it has been remained a subject of investigation
      and conjecture since the nineteenth century. Two fundamental mechanisms have been
      proposed to explain ventricular alteration. The first, based on the Frank
      Starling mechanism, proposes beat-to-beat alteration in end-diastolic volume
      accounted for the alternating contractile force. The second proposed mechanism
      which explains the physiology of pulsus alternans involves the abnormal calcium
      handling by cardiac myocytes. To the best of our knowledge, biventricular
      alternans in pulmonary embolism has not been previously reported in the medical
      literature. We present and discuss the mechanisms of pulsus alternans and its
      clinical implications. 

PMID- 24303493
TI  - Long lasting response to second-line everolimus in kidney cancer.
AB  - In the case presented here, everolimus was administered after first line therapy
      with sunitinib in a patient with metastatic renal cell carcinoma. The safety
      profile was excellent. The prolonged progression-free survival (PFS) obtained
      with everolimus in this case is of peculiar interest, as it is a multiple of the
      median PFS obtained in with everolimus in the regulatory trial. Such finding
      suggests that a subset of patients with renal cell carcinma may particularly
      benefit from everolimus. 

PMID- 24303494
TI  - Hypoglycemia associated with fluoxetine treatment in a patient with type 1
      diabetes.
AB  - We report on a patient with type 1 diabetes mellitus who presented with recurrent
      episodes of hypoglycemia and a marked reduction in her daily insulin requirements
      after introduction of fluoxetine. This 25-year-old Caucasian woman had been
      followed up at the outpatient clinic for type 1 diabetes mellitus and pre
      pregnancy care. She used a continuous subcutaneous insulin infusion with lispro
      and her daily insulin dose was 0.5 IU/kg per day. She had no chronic diabetic
      complications or hypoglycemia unawareness. Fluoxetine at a daily dose of 20 mg
      had been started because of depressive symptoms and within one week, she
      presented recurrent hypoglycemic episodes that prompted a progressive reduction
      in the insulin dose down to 0.3 IU/kg per day. The reduced insulin requirements
      continued during the period of fluoxetine treatment while glycated hemoglobin
      remained stable. She had no concurrent additional cause to explain the reduced
      insulin requirements. After fluoxetine was stopped, insulin requirements
      progressively increased and returned to the patient's usual dose. 

PMID- 24303495
TI  - Burr hole evacuation for infratentorial subdural empyema.
AB  - Infratentorial empyema is a life threatening condition and constitutes a
      neurosurgical emergency. Purulent mastoiditis and medial otitis is the most
      common origin and a thorough eradication of the purulent foci is mandatory.
      Decompression craniectomy has been primarily advised in the literature as the
      gold standard of the surgical treatment but burr hole evacuation when there the
      lack of cerebellar edema is less invasive and deemed equally efficient in the few
      reported cases. This is the report of a seventeen year old female who presented
      in a comatose state due to infratentorial empyema with acute hydrocephalus and
      who improved immediately after burr hole evacuation. Details of the surgical
      procedures are given. Mastoidectomy was completed, with the patient under
      combined antibiotherapy. She leads a normal life now, more than six years after
      surgery. 

PMID- 24303496
TI  - A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal
      tract showing extensive plasma cell differentiation with prominent Russell
      bodies.
AB  - A 73-year-old Japanese woman was hospitalized for detailed examination of nausea,
      diarrhea and loss of appetite. Atypical erosion in the ileum was found on
      endoscopy. Biopsy of this erosion showed proliferation of cells containing
      numerous Russell bodies. Differential diagnoses considered were Russell body
      enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative
      small intestinal disease (IPSID) and mucosa-associated lymphoid tissue (MALT)
      lymphoma. The cells containing prominent Russell bodies showed diffuse positivity
      for CD79a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68.
      Russell bodies were diffusely positive for lambda light chain, but negative for
      kappa light chain, and immunoglobulin (Ig) G, IgA and IgM. Based on these
      findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were
      ruled out. As the tumor formed no mass lesions and was restricted to the
      gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation
      was finally diagnosed. The patient showed an unexpectedly aggressive clinical
      course. The number of atypical lymphocytes in peripheral blood gradually
      increased and T-prolymphocytic leukemia (T-PLL) emerged. The patient died of T
      PLL 7 mo after admission. Autopsy was not permitted. 

PMID- 24303497
TI  - Fine needle aspiration diagnosis of isolated pancreatic tuberculosis: A case
      report.
AB  - Tuberculosis (TB) involving the pancreas are uncommon, especially when present in
      immunocompetent hosts. Pancreatic TB is more frequently associated with miliary
      TB or widely disseminated disease. Pancreatic TB may present as cystic or solid
      pancreatic masses, pancreatic abscess or acute or chronic pancreatitis. Majority
      of the cases are diagnosed after surgical exploration for presumed pancreatic
      malignancy and pre-operative diagnosis is quite difficult. However, improvement
      in imaging techniques and the resulting image-guided interventions gradually can
      obviate the need for more invasive diagnostic surgical procedures and expedite
      the planning of therapy. Herein, we report a rare case of isolated pancreatic TB
      which presented with pancreatic mass lesion in an immunocompetent host. Diagnosis
      was made by contrast enhanced computed tomography and guided fine needle
      aspiration of the pancreatic mass which revealed acid-fast bacilli on Ziehl
      Neelsen stain. The case was treated successfully with antituberculous drugs.
      Pancreatic tuberculosis should be considered in the differential diagnosis of a
      pancreatic mass when the patient is young, residing in the endemic zone of
      tuberculosis. Every attempt should be made to diagnose the cases to prevent
      unnecessary operation. 

PMID- 24303498
TI  - Recurrent epithelial ovarian cancer and hormone therapy.
AB  - The role of hormone therapy in the treatment of ovarian cancer is not clear. Data
      on the efficacy and safety of antiestrogens and aromatase inhibitors in recurrent
      ovarian cancer have been accumulated through phase II clinical studies. Most of
      these studies were conducted in platinum-resistant recurrent ovarian cancer, and
      although complete response rates were not high, reported adverse events were low.
      If administered to patients who are positive for estrogen receptors, hormone
      therapy may become a viable option for the treatment of recurrent ovarian cancer.

PMID- 24303499
TI  - Infliximab for the treatment of pouchitis.
AB  - Pouchitis is not a rare complication that develops after an ileal-pouch
      anastomosis, performed after colectomy in patients refractory to treatment or
      with complicated ulcerative colitis. This condition may become chronic and
      unresponsive to medical therapies, including corticosteroids, antibiotics and
      probiotics. The advent of biological therapies (tumor necrosis factor-alpha
      inhibitors) has changed the course of these complications. In particular, in
      these cases, infliximab (IFX) may represent a safe and effective therapy in order
      to avoid the subsequent operation for a permanent ileostomy. This article reviews
      the therapeutic effects of one of the most widely used anti-tumor necrosis factor
      alpha molecules, IFX, for the treatment of complicated pouchitis (refractory to
      conventional treatment and/or fistulizing). 

PMID- 24303500
TI  - Dynamic mechanical allodynia following finger amputation: Unexpected skin
      hyperinnervation.
AB  - The development of chronic pain after amputations is not an uncommon event. In
      some cases the most disabling problem is represented by the symptom called
      dynamic mechanical allodynia, characterized by the painful sensation evoked by
      gently stroking the skin. Despite the growing interest in understanding pain
      mechanisms, little is known about the mechanism sustaining this peculiar type of
      pain. We present here the case of a 53-year-old female patient who complained of
      severe tactile allodynia in the hand after amputation of her left second finger,
      resistant to several medical and surgical treatments. In order to gain
      information about the pain mechanism, two neurodiagnostic skin biopsies were
      obtained from the area of tactile allodynia and from the contralateral, normal
      skin area. Skin biopsies showed an unexpected increased innervation of the
      allodynic skin compared to the contralateral, normal skin area (+ 80.1%).
      Hyperinnervation has been proposed as a mechanism of pain following nerve
      lesions, but the increased innervation described here could be also attributed to
      neuronal plasticity occurring in chronic inflammatory conditions. Independently
      from the uncertain cause of the epidermal hyperinnervation, in this patient we
      tried to reduce the elevated number of epidermal nerve fibres by treating the
      skin with topical capsaicin (0.075%) three times a day, and obtained a persistent
      pain relief. In conclusion, neurodiagnostic skin biopsy might represent an useful
      tool for detecting derangements of epidermal innervation in patients with dynamic
      mechanical allodynia and can help to select an individually tailored therapeutic
      strategy in such difficult clinical conditions. Further studies are needed to
      clarify this issue and try to gain better understanding of chronic pain
      mechanisms in patients who underwent finger amputation. 

PMID- 24303501
TI  - Cystic benign teratoma of the neck in adult.
AB  - Teratomas are embryonal neoplasms that arise when totipotential germ cells escape
      the developmental control of primary organizers and give rise to tumors
      containing tissue derived from all three blastodermic layers. Teratomas have been
      reported to occur in various sites and organs. Teratoma of the cervical neck are
      relatively rare in adulthood. It usually extends from the neck to the thoracic
      cavity causing local mass effect. In most of the cases intrauterine diagnosis is
      possible by ultrasound. Because of dyspnea due to mass effect, this condition is
      treated promptly after birth. However cases of teratoma in adulthood with
      supraclavicular localization have been reported rarely in the literature. The
      presented case is of a 25-year-old female with a cervical mass. Histological
      examination revealed a benign mature teratoma. The patient has been disease free
      for more than nine years after surgical removal of a neck teratoma. 

PMID- 24303502
TI  - Use of central venous saturation monitoring in a patient with pediatric cardiac
      beriberi.
AB  - The patient was a 1-year-and-4-mo-old boy. He had drunk about 1 L of an isotonic
      drink for infants daily since about 10 mo after birth. He was examined by a local
      doctor due to anorexia and vomiting, found to have cardiomegaly, and transported
      to our hospital with suspected myocarditis. After admission, the patient showed
      polypnea, a decreased level of consciousness, and marked metabolic acidosis and
      lapsed into circulatory insufficiency, requiring catecholamine administration,
      endotracheal intubation, and extracorporeal membrane oxygenation. Initially, low
      output heart failure due to acute myocarditis was suspected, but the central
      venous oxygen saturation was high, at 82%. Considering high-output heart failure
      to be more likely, we evaluated its cause and noted, by urinary organic acid
      analysis, increases in lactate, pyruvate, 3-OH-butyrate, acetoacetate, metabolic
      products of branched-chain amino acids, 2-ketoglutarate, 2-OH-glutarate, 2-keto
      adipate, and 2-OH-adipate. Since the vitamin B1 level was reduced to 12 ng/mL
      (normally 20-50 ng/mL), a diagnosis of cardiac beriberi due to vitamin B1
      deficiency was made. When unexplained heart failure is observed in children,
      cardiac beriberi must be excluded as a differential diagnosis of myocarditis and
      cardiomyopathy. The measurement of the central venous oxygen saturation may be
      useful for the diagnosis. 

PMID- 24303503
TI  - Comparative study of exome copy number variation estimation tools using array
      comparative genomic hybridization as control.
AB  - Exome sequencing using next-generation sequencing technologies is a cost
      efficient approach to selectively sequencing coding regions of the human genome
      for detection of disease variants. One of the lesser known yet important
      applications of exome sequencing data is to identify copy number variation (CNV).
      There have been many exome CNV tools developed over the last few years, but the
      performance and accuracy of these programs have not been thoroughly evaluated. In
      this study, we systematically compared four popular exome CNV tools (CoNIFER,
      cn.MOPS, exomeCopy, and ExomeDepth) and evaluated their effectiveness against
      array comparative genome hybridization (array CGH) platforms. We found that exome
      CNV tools are capable of identifying CNVs, but they can have problems such as
      high false positives, low sensitivity, and duplication bias when compared to
      array CGH platforms. While exome CNV tools do serve their purpose for data
      mining, careful evaluation and additional validation is highly recommended. Based
      on all these results, we recommend CoNIFER and cn.MOPs for nonpaired exome CNV
      detection over the other two tools due to a low false-positive rate, although
      none of the four exome CNV tools performed at an outstanding level when compared
      to array CGH. 

PMID- 24303505
TI  - "Decent respect": an update on United's October surprise.

PMID- 24303504
TI  - Association of the receptor for advanced glycation end products gene
      polymorphisms and circulating RAGE levels with diabetic retinopathy in the
      Chinese population.
AB  - OBJECTIVES: This study investigated the association between polymorphisms in the
      receptor for advanced glycation end products (RAGE) gene and the susceptibility
      to diabetic retinopathy (DR) in a Chinese population and identified a correlation
      between serum-soluble RAGE (sRAGE) levels and DR risk. MATERIALS AND METHODS: We
      enrolled 1040 patients with type 2 diabetes mellitus: 372 patients with DR and
      668 without retinopathy (NDR). All polymorphisms were genotyped by time-of-flight
      mass spectrometry. Serum levels of sRAGE were assayed by enzyme-linked
      immunosorbent assays. The interaction of SNPs was analyzed by multifactor
      dimensionality reduction (MDR). RESULTS: The frequency of the SS genotype for the
      G82S polymorphism was 12.4% in the DR group and 6.6% in the NDR group; this
      difference was significant. G82S was associated with sRAGE levels. Specifically,
      after adjustments for age, sex, duration, and glucose metabolism, serum sRAGE
      levels were significantly higher in DR subjects with the S/S genotype than in NDR
      subjects in general. In the DR group, subjects with the G/S genotype had lower
      sRAGE levels than subjects with the G/G or S/S genotype (P < 0.01). The best
      multilocus genetic interaction model was assessed using the MDR method; 2184A/G,
      1704G/T, G82S, and -429T/C were identified. CONCLUSIONS: The findings suggest
      that the G82S polymorphism in the RAGE gene is associated with DR risk, and G82S
      was associated with circulating levels of sRAGE. The mechanism by which G82S
      polymorphism modulates the sRAGE levels remains to be elucidated.

PMID- 24303506
TI  - Altruism and my nine gallons of blood.

PMID- 24303507
TI  - History issues a cautious summons to reason.

PMID- 24303508
TI  - ACC/AHA new cholesterol management guidelines: what's a doc to do?

PMID- 24303509
TI  - Motorcycle helmet use in Rhode Island.
AB  - Motorcycle crashes are a major public health concern and place economic stresses
      on the health care system. Helmets have been shown to reduce both motorcycle
      related fatalities and head injuries. Universal motorcycle helmet laws in other
      states have shown to be effective at increasing helmet use. The current Rhode
      Island motorcycle helmet law does not require every motorcycle rider to wear a
      helmet. Given the number of deaths and injuries that could be prevented, public
      health efforts to increase helmet use through education and legislation should be
      considered for review.

PMID- 24303510
TI  - Doctor questions requiring flu shots for health care workers.

PMID- 24303511
TI  - Impact of nursing-centered HIV testing using standing orders in RI.

PMID- 24303512
TI  - Emergency Medical Services (EMS). More than a ride to the hospital--examining the
      continuing evolution of a complex, coordinated response system.

PMID- 24303513
TI  - An overview of prehospital emergency medical services.
AB  - Prehospital emergency medical services (EMS) provide lifesaving care daily in the
      United States. This article outlines the development of this vital public safety
      endeavor and highlights the characteristics of the Rhode Island system.

PMID- 24303514
TI  - Physician medical direction of emergency medical services.
AB  - Emergency medical services (EMS) bring the practice of emergency medicine
      directly to the homes of patients. Physician guidance of system development and
      provider practice can enhance the quality of care. This article provides an
      overview of issues in the development of EMS system oversight in the United
      States in general, and in Rhode Island.

PMID- 24303515
TI  - Emergency medical technician education and training.
AB  - Emergency Medical Services (EMS) training and education are vital and vibrant
      aspects of a young and evolving profession. This article provides a perspective
      on this effort in the United States and reviews current activity in Rhode Island.

PMID- 24303516
TI  - The Rhode Island Life Saving Score (RILSS)--a proposed life-saving definition for
      EMS and emergency medicine.
AB  - Emergency Medical Services (EMS) and Emergency Medicine staff are often described
      as life-saving providers, but there is no generally accepted objective definition
      of a life saved by these providers. Therefore, a proposed definition is
      described. Development of this definition began with conceptual rules, followed
      by a survey of physician EMS medical directors, and then by the development of a
      tool to implement the definition, and measure its validity and reliability
      through a review of 100 critical care transport EMS patient charts.

PMID- 24303517
TI  - Critical care transport.
AB  - Critical care transport (CCT) is the segment of the Emergency Medical Services
      (EMS) system that transports patients who are critically ill or injured. Nearly
      1,000 medical helicopters affiliated with over 300 transport programs, hundreds
      of fixed-wing aircraft, and many, many ground ambulances assisting adult,
      pediatric and neonatal CCT teams are operating in the United States.1 This
      article reviews the history of and indications for CCT, team qualifications,
      vehicle options, safety, CCT system design, and physician involvement in CCT. It
      concludes with a brief review of CCT services in Rhode Island.

PMID- 24303518
TI  - Spontaneous coronary dissection in polycystic kidney disease.
AB  - We report a case of a 46-year-old woman with hypertension and autosomal dominant
      polycystic kidney disease who presented with chest pain and was found to have
      spontaneous coronary artery dissection (SCAD) on diagnostic catheterization. We
      review the pathogenesis, management and prognosis of SCAD. We conclude that in
      patients with polycystic kidney disease who present with angina pectoris and
      positive cardiac biomarkers, coronary artery dissection should be considered.

PMID- 24303519
TI  - Kikuchi Fujimoto disease (KFD) in a 31-year-old woman.

PMID- 24303520
TI  - Health information technology (HIT) adoption and use by Rhode Island advance
      practice registered nurses and physician assistants, 2013.

PMID- 24303522
TI  - Editor's Introduction.

PMID- 24303523
TI  - Special issue: Proceedings of the 19th International Symposium on Hemodialysis.
      Preface.

PMID- 24303521
TI  - Evaluation of Raman spectroscopy for diagnosing EGFR mutation status in lung
      adenocarcinoma.
AB  - Somatic mutations in the epidermal growth factor receptor (EGFR) gene were
      associated with sensitivity to small molecule tyrosine kinase inhibitors for
      patients with lung adenocarcinomas. In this research, EGFR mutation status was
      analyzed by DNA sequencing in 153 lung adenocarcinoma tissues. Of these, 75
      samples carried EGFR mutations, including 29 with E19del mutation, 33 with L858R
      mutation, 7 with T790M mutation, and 6 with multiple mutations. Then, 30 samples
      including 10 with wild type (wt)-EGFR, 10 with L858R and 10 with E19del mutations
      were selected for Raman and immunohistochemistry (IHC) analyses. After removing
      the spectra from normal and non-mutated regions, 441 spectra were found
      appropriate for Raman analysis: 149 from wt-EGFR, 135 from L858R and 157 from
      E19del mutations. The Raman peaks at 675, 1107, 1127 and 1582 cm(-1) were
      significantly increased in wt-EGFR tissues which can be attributed to specific
      amino acids and DNA. The Raman peaks at 1085, 1175 and 1632 cm(-1) assigned to
      arginine were slightly increased in L858R tissues. The overall intensity of
      E19del tissues was weaker than others due to exon 19 deletion that removes
      residues 746-750 of the expressed protein. Principal component analysis (PCA) and
      support vector machine (SVM) were applied for final prediction. The PCA/SVM
      algorithm yielded an overall accuracy of 87.8% for diagnosing L858R or E19del
      from wt-EGFR tissues. Finally, RS provides a simple, rapid and low-cost procedure
      based upon the molecular signatures for predicting EGFR mutation status.

PMID- 24303524
TI  - Detection of single nanoparticles and lentiviruses using microcavity resonance
      broadening.
AB  - A new label-free sensing mechanism is demonstrated experimentally by monitoring
      the whispering-gallery mode broadening in microcavities. It is immune to both
      noise from the probe laser and environmental disturbances, and is able to remove
      the strict requirement for ultra-high-Q mode cavities for sensitive nanoparticle
      detection. This ability to sense nanoscale objects and biological analytes is
      particularly crucial for wide applications.

PMID- 24303525
TI  - [Mag. Dr. Judith Leitner: Medical University of Vienna Researcher of the Month,
      October 2013].

PMID- 24303526
TI  - Retraction notice to "Microbial pollution in wildlife: linking agricultural
      manuring and bacterial antibiotic resistance in red-billed choughs"
      [Environmental research 109 (2009)405-412].

PMID- 24303527
TI  - Retraction notice to "Interaction of somatostatin receptor-2 and neuropeptide Y
      receptor-1 in mice dorsal root ganglion neurons on the pinch-nerve injury model"
      [Pharmacology, Biochemistry and Behavior 105 (2013) 71-75].

PMID- 24303528
TI  - Reflections: neurology and the humanities: personal health information in verse.

PMID- 24303529
TI  - Author Response.

PMID- 24303530
TI  - Cola and honey: exploring food riddles in rhythm disturbances.

PMID- 24303531
TI  - Author Response.

PMID- 24303532
TI  - Perioperative statins trial: the climax of a new approach to atrial fibrillation.

PMID- 24303533
TI  - Carbon nanotube sensors could aid drug manufacturing.

PMID- 24303534
TI  - Partnership extended in the fight against neglected diseases.

PMID- 24303536
TI  - APIC guide highlights role of ambulatory care in disaster response.

PMID- 24303535
TI  - The role of estrogen receptor-alpha in estrogen-mediated regulation of basal and
      exercise-induced Hsp70 and Hsp27 expression in rat soleus.
AB  - We examined the influence of estrogen receptor-alpha (ERalpha) activation on
      estrogen-mediated regulation of heat shock proteins 70 (Hsp70) and 27 (Hsp27) in
      soleus. Ovariectomized rats received estrogen (EST), an ERalpha agonist (propyl
      pyrazole triol, PPT), both (EST+PPT), or a sham, and they served as either
      unexercised controls or were subjected to exercise by having to run downhill (17
      m/min, -13.5 degrees  grade) for 90 min. At 72 h postexercise, soleus muscles
      were removed and either immunohistochemically stained for Hsp70 and myosin heavy
      chain or homogenized for Western blotting for Hsp70 and Hsp27. Elevated (p <
      0.05) basal Hsp70 in both type I and II fibres in the unexercised EST, PPT, and
      EST+PPT groups relative to unexercised sham animals was noted. Compared with
      Hsp70 levels in the unexercised animals, that in exercised animals was elevated
      (p < 0.05) in both sham and PPT groups but not in EST and EST+PPT groups. Western
      blot determined that Hsp27 levels were not significantly different between
      groups. Hence, the ability of estrogen to augment resting type I and type II
      muscle fibre Hsp70 content is primarily mediated via muscle ERalpha. However, the
      blunted Hsp70 response following damaging exercise in estrogen-supplemented
      animals does not appear to be fully accounted for by ERalpha-mediated effects.

PMID- 24303537
TI  - ASCs dodge wind, water, and infection risk.

PMID- 24303538
TI  - Family focused. Child-friendly design pays off for young patients and their
      families.

PMID- 24303539
TI  - Hands down.

PMID- 24303540
TI  - It's complicated.

PMID- 24303541
TI  - Holiday feast.

PMID- 24303542
TI  - The art of indulging.

PMID- 24303543
TI  - Is the two-midnight rule much ado about nothing?
AB  - The Centers for Medicare & Medicaid Services has declared that stays that span
      two midnights should be presumed to be inpatient stays, but case managers still
      need to make sure patients meet inpatient criteria and that the documentation is
      complete. Physicians must certify medical necessity, sign, date, and time the
      admission, and include a treatment plan and the anticipated length of stay.
      Physician documentation must be accurate, detailed and give a complete picture of
      what's going on with the patient or hospitals could face significant payment
      implications. Medicare auditors still will be scrutinizing the records and are
      likely to continue to target one-day stays and two-day stays for medical
      necessity.

PMID- 24303544
TI  - Work with physicians to ensure record is complete.

PMID- 24303545
TI  - Medicare audit program still going strong.

PMID- 24303546
TI  - Redesign links CMs, primary care.
AB  - At WellSpan Health, teams that include hospital-based case managers and social
      workers, and health coaches located in physician offices, work together to
      coordinate care. The case managers and social workers are assigned by physician
      and spend most of their time in the hospital, but are expected to spend a target
      of two hours a week at the WellSpan Medical Group physician practices. Practices
      that are not part of the WellSpan Medical Group are assigned a case manager and a
      social worker who follow their patients in the hospital but do not visit the
      practice. The initiative promotes communication and collaboration between the
      hospital level of care and primary care.

PMID- 24303547
TI  - Team approach improves care coordination.

PMID- 24303548
TI  - Helping patients understand their insurance.

PMID- 24303549
TI  - [Virtual reality simulations and postgraduate education in Sumery].

PMID- 24303550
TI  - Epigenetic regulation of melanoma tumor suppressor miRNA-124a.

PMID- 24303551
TI  - TFPI2 methylation can serve as an epigenetic biomarker of metastatic melanoma.

PMID- 24303552
TI  - Circumvention of drug-resistance via decitabine-mediated DNMT1 depletion.

PMID- 24303553
TI  - Role of miR-18b/MDM2/p53 circuitry in melanoma progression.

PMID- 24303554
TI  - Epigenetic fine-tuning of NF-kappaB-Sox9 circuitry in cancer stem cells.

PMID- 24303555
TI  - Regulation of the apoptotic activity of the ING member of histone
      acetyltransferase and deacetylase complexes.

PMID- 24303556
TI  - Prevalence of DNA methyltransferase in breast cancer by  SNP analysis.

PMID- 24303557
TI  - Epigenetic regulation of retinoic acid susceptibility in leukemia.

PMID- 24303558
TI  - Epigenetic biomarker of metastatic melanoma.

PMID- 24303560
TI  - PRC2 dysfunction through multiple mechanisms in myeloid malignancies.

PMID- 24303561
TI  - [Not Available].

PMID- 24303562
TI  - H3K27me3 inhibitor: a potential new therapy for cytogenetically normal refractory
      cytopenia with multilineage dysplasia.

PMID- 24303563
TI  - [Not Available].

PMID- 24303564
TI  - [Not Available].

PMID- 24303565
TI  - [Not Available].

PMID- 24303566
TI  - Retraction.

PMID- 24303567
TI  - [Molecular epidemiological study of Rickettsia raoultii in ticks from Xinjiang,
      China].

PMID- 24303568
TI  - [Prevalence of GB virus type C viraemia and subtype infection in MSM population
      in Beijing].

PMID- 24303569
TI  - Attachment security, personality, and adjustment of elementary school children.
AB  - Children's development is assumed to be closely related to their attachment
      security and their personality. The authors' aim was to examine the joint
      contribution of attachment security and personality traits to children's
      adjustment by examining diverse children's outcomes (emotional symptoms, social
      functioning, and behavioral problems) and using various perspectives (children,
      parents, and teachers). The sample comprised 247 8-12-year-old children from low
      socioeconomic status neighborhoods. Personality and attachment contribute to the
      different domains of adjustment. In cases of moderation, attachment security
      moderates the implications of personality traits on children's adjustment. The
      findings highlight the contribution of positive personality tendencies in playing
      down the difficulties of insecurely attached children.

PMID- 24303570
TI  - Adolescent sense of control: a downward extension of the Shapiro Control
      Inventory to pre- and early adolescents.
AB  - The most commonly used measures of perceived control for young adolescents are
      dated, psychometrically flawed, or focused on particular domains. To address the
      need for a general purpose measure of control for this age range, the overall
      sense of control (OSOC) and the domains of control (DOC) subscales of the Shapiro
      Control Inventory (D. H. Shapiro, 1994), designed for use with adults, were
      modified. Exploratory factor analyses suggested that the adapted OSOC and DOC
      scales consisted of internally consistent 1-factor structures, accounting for 32%
      and 29% of the variance, respectively. In Study 1, results from 310
      preadolescents (9-13 years old) indicated that a higher sense of control was
      related to lower stress, OSOC, r(308) = -.52, p < .001; DOC, r(308) = -.23, p <
      .001; and depression, OSOC, r(308) = -.63, p < .001; DOC, r(308) = -.33, p <
      .001. In study 2, results from 195 adolescents (11-15 years old) showed that a
      higher sense of control was associated with lower stress, r(193) = -.55, p <
      .001, and depression, r(193) = -.60, p < .001, concurrently. The results suggest
      that these 2 revised measures of adolescent perceived control exhibited good
      content and predictive validities.

PMID- 24303571
TI  - Disentangling fine motor skills' relations to academic achievement: the relative
      contributions of visual-spatial integration and visual-motor coordination.
AB  - Recent research has established a connection between children's fine motor skills
      and their academic performance. Previous research has focused on fine motor
      skills measured prior to elementary school, while the present sample included
      children ages 5-18 years old, making it possible to examine whether this link
      remains relevant throughout childhood and adolescence. Furthermore, the majority
      of research linking fine motor skills and academic achievement has not determined
      which specific components of fine motor skill are driving this relation. The few
      studies that have looked at associations of separate fine motor tasks with
      achievement suggest that copying tasks that tap visual-spatial integration skills
      are most closely related to achievement. The present study examined two separate
      elements of fine motor skills--visual-motor coordination and visual-spatial
      integration--and their associations with various measures of academic
      achievement. Visual-motor coordination was measured using tracing tasks, while
      visual-spatial integration was measured using copy-a-figure tasks. After
      controlling for gender, socioeconomic status, IQ, and visual-motor coordination,
      and visual-spatial integration explained significant variance in children's math
      and written expression achievement. Knowing that visual-spatial integration
      skills are associated with these two achievement domains suggests potential
      avenues for targeted math and writing interventions for children of all ages.

PMID- 24303572
TI  - Epistemological development and judgments and reasoning about teaching methods.
AB  - Children's, adolescents', and adults' (N = 96 7-8, 10-11, and 13-14-year-olds and
      university students) epistemological development and its relation to judgments
      and reasoning about teaching methods was examined. The domain (scientific or
      moral), nature of the topic (controversial or noncontroversial), and teaching
      method (direct instruction by lectures versus class discussions) were
      systematically varied. Epistemological development was assessed in the
      aesthetics, values, and physical truth domains. All participants took the domain,
      nature of the topic, and teaching method into consideration in ways that showed
      age-related variations. Epistemological development in the value domain alone was
      predictive of preferences for class discussions and a critical perspective on
      teacher-centered direct instruction, even when age was controlled in the
      analysis.

PMID- 24303573
TI  - Autonomy, filial piety, and parental authority: a two-year longitudinal
      investigation.
AB  - A 2-year longitudinal study was conducted to test 3 causal models about
      adolescent autonomy, filial piety, beliefs about parental authority, and
      obedience in terms of personal, prudential, and multifaceted issues. Four hundred
      and thirty-six students from 10 junior and senior high schools in Taiwan (boys, n
      = 223; senior high school, n = 211) participated in the study. Hypothesis I
      predicted that autonomy (individuating autonomy vs. relating autonomy) would
      positively correlate with beliefs about authority legitimacy and obligation to
      obey, but was not supported. Hypothesis 2 predicted that filial piety
      (authoritarian piety vs. reciprocal piety) would positively associate with
      authority beliefs, and was partially supported. Authoritarian piety showed the
      positive relation with authority beliefs. Hypothesis 3 predicted that beliefs
      about authority legitimacy and obligation to obey would positively associate with
      obedience, and was supported. Hypothesis 4 predicted that age might moderate the
      structure models across domains, but the results indicated that age did not
      moderate the structural model in the prudential and multifaceted domains. The
      overall findings of this study reveal that adolescent beliefs about authority
      serve as a mediator between authoritarian piety and obedience, suggesting that
      traditional piety still has an influence on parent-child interaction in today's
      society.

PMID- 24303574
TI  - Children's understanding and experience of mixed emotions: the roles of age,
      gender, and empathy.
AB  - The present study examined the development of children's ability report
      understanding and experiencing allocentric mixed emotions, and explored the
      relation of gender and empathic ability to these skills. Participants (128
      elementary school-aged children [63 boys, 65 girls]) were shown a movie clip with
      bittersweet themes to elicit mixed emotions. Findings from this study are
      consistent with prior research (Larsen, To, & Fireman, 2007), supporting a
      developmental progression in children's ability to both understand and report
      experiencing mixed emotions, with the two as distinct skills and children
      reporting understanding earlier than experiencing of emotions. Consistent with
      previous research, girls performed significantly better on the emotion experience
      task. Finally, results provided evidence that empathy partially mediates the
      relationship between age and reports of mixed emotion experience, but no evidence
      that empathy plays a role in mixed emotional understanding.

PMID- 24303575
TI  - Information transmission in young children: when social information is more
      important than nonsocial information.
AB  - The authors' aim was to use a highly novel open diffusion paradigm to investigate
      the transmission of social information (i.e., gossip) and general knowledge
      within 2 groups of 10- and 11-year-old children. Four children, 2 from each
      group, acted as a primed information source, selected on the basis of sex and
      dominance ranking (high or low) within the group. Each source received 1 piece of
      gossip and 1 piece of general knowledge from the experimenter during natural
      class interaction, and the information was allowed to diffuse naturally within
      the group. Results revealed that gossip was transmitted more frequently than
      knowledge, and that male sources were more likely to transmit gossip than female
      sources. The relationship between characteristics of the source, and
      characteristics of the gossip recipient, also appeared influential with the
      dominant male source transmitting gossip to exclusively to friends, and the
      nondominant male source transmitting to individuals of higher peer regard than
      themselves.

PMID- 24303576
TI  - The relationship between parenting and the economic orientation and behavior of
      Norwegian adolescents.
AB  - Little is known about the economic socialization of children and adolescents and
      the role of parents in this process. The authors' purpose was to explore the role
      of parenting in the intergenerational transfer of economic orientation and
      economic behavior. More specifically, they studied the link between four
      parenting dimensions (parental warmth-responsiveness, behavioral control,
      psychological control, autonomy granting), three parenting styles (authoritative,
      authoritarian, and neglectful) and adolescents' conscientiousness, future time
      perspective, and present hedonistic orientation. The authors also studied the
      relationships between these dispositions and the adolescents' spending
      preferences and ability to control spending. They used data collected from 14-16
      year-olds (n = 597) and their parents (n = 469) in Norway. Results showed that
      adolescents who perceived their parents as psychologically controlling were less
      future oriented and conscientious, and were more present hedonistic oriented than
      others, while adolescents who perceived their parents as responsive, autonomy
      granting, and controlling of behavior were more future orientated and
      conscientious than others. Adolescents' scores for conscientiousness and future
      orientation were negatively associated with preferences for spending and
      positively with the ability to control spending, while the opposite relationships
      were found with respect to a present hedonistic orientation. Parental style was
      also found to be important for the future educational plans of adolescents, and
      plans for higher education were more frequent among adolescents who characterized
      their parents as authoritative than among those who perceived their parents as
      neglectful. Implications of the findings for economic socialization are
      discussed.

PMID- 24303577
TI  - Preschoolers' emotion expression and regulation: relations with school
      adjustment.
AB  - Children's expression and regulation of emotions are building blocks of their
      experiences in classrooms. Thus, the authors' primary goal was to investigate
      whether preschoolers' expression or ability to regulate emotions were associated
      with teachers' ratings of school adjustment. A secondary goal was to investigate
      how boys and girls differed across these associations. Children's social
      emotional behaviors in Head Start and private childcare center classrooms were
      observed, and using a series of measures, teachers' ratings of children's social
      competence, attitudes toward school, positive teacher relationships, and
      cooperative participation were collected. Three factors of children's school
      adjustment were extracted from these indicators. A series of hierarchical
      regressions revealed that emotion expression and regulation were indeed
      associated with children's reported school adjustment, with the strongest
      associations stemming from children's negative emotion expression and their
      emotion dysregulation. Many of these associations were also different for boys
      and girls. The results corroborate and extend the authors' earlier findings, and
      have implications for social-emotional programming to maximize children's early
      school success.

PMID- 24303578
TI  - Gender, g, gender identity concepts, and self-constructs as predictors of the
      self-estimated IQ.
AB  - In all 102 participants completed 2 intelligence tests, a self-estimated domain
      masculine (DMIQ) intelligence rating (which is a composite of self-rated
      mathematical-logical and spatial intelligence), a measure of self-esteem, and of
      self-control. The aim was to confirm and extend previous findings about the role
      of general intelligence and gender identity in self-assessed intelligence. It
      aimed to examine further correlates of the Hubris-Humility Effect that shows men
      believe they are more intelligent than women. The DMIQ scores were correlated
      significantly with gender, psychometrically assessed IQ, and masculinity but not
      self-esteem or self-control. Stepwise regressions indicated that gender and
      gender role were the strongest predictors of DMIQ accounting for a third of the
      variance.

PMID- 24303579
TI  - Paternal family expressiveness as a mediator between father's dispositional
      optimism and child's dispositional optimism.
AB  - Although dispositional optimism serves as a resource for psychological and
      physical well-being, very little research has explored how to promote child
      dispositional optimism within the family context. The authors evaluated paternal
      emotional expressiveness within the family as a mediator of the association
      between father's and child's dispositional optimism. Participants were 422 father
      (M age = 44.97 years, SD = 4.21 years)-child (M age = 11.75 years, SD = 0.77
      years) dyads in South Korea. Results showed that fathers' dispositional optimism
      was positively linked to their expressiveness, which in turn was positively
      linked to their children's dispositional optimism. No significant gender or
      socioeconomic status differences were found. The findings have important
      implications for future research and for preventive interventions.

PMID- 24303580
TI  - Relationships of cognitive and metacognitive learning strategies to mathematics
      achievement in four high-performing East Asian education systems.
AB  - The authors examined the relationships of cognitive (i.e., memorization and
      elaboration) and metacognitive learning strategies (i.e., control strategies) to
      mathematics achievement among 15-year-old students in 4 high-performing East
      Asian education systems: Shanghai-China, Hong Kong-China, Korea, and Singapore.
      In all 4 East Asian education systems, memorization strategies were negatively
      associated with mathematics achievement, whereas control strategies were
      positively associated with mathematics achievement. However, the association
      between elaboration strategies and mathematics achievement was a mixed bag. In
      Shanghai-China and Korea, elaboration strategies were not associated with
      mathematics achievement. In Hong Kong-China and Singapore, on the other hand,
      elaboration strategies were negatively associated with mathematics achievement.
      Implications of these findings are briefly discussed.

PMID- 24303581
TI  - A conversation with Dr. Mary Wakefield on the subject of the Affordable Care Act.
      Interview by Gloria J McNeal.

PMID- 24303582
TI  - Lifestyle management of cardiovascular risk factors in African American women.
AB  - African American women have the highest prevalence of obesity in the nation when
      compared to Caucasian and Hispanic women. The purpose of this project was to
      evaluate the effect of nutrition education and counseling on weight loss, blood
      pressure, self- efficacy and perception of power. The project was a 12 week
      community-based lifestyle intervention program designed to provide counseling and
      education on increasing physical activity, dietary intake of fruits and
      vegetables while, decreasing dietary intake salt and fat. The results showed that
      the women, who engaged in all aspects of the program, were able to lose weight
      and lower their blood pressure.

PMID- 24303583
TI  - Motivators to engage in health promotion activities by low-income black fathers.
AB  - There has been increasing concern about the health status of low-income Black
      fathers. Little is known about their motivators to participate in health
      promotion activities. This descriptive qualitative research study explored these
      motivators. Focus groups were used to gather the data. Themes included avoiding
      specific diseases, helping others, a personal desire to learn, and modeling
      positive behaviors. These findings provide baseline data that might be used to
      develop community interventions targeting this group. Additional work will focus
      on validating these results and further exploration of some of the motivators
      verbalized by these participants.

PMID- 24303584
TI  - Developing a clinical research associate training program at Dillard University:
      the impact of collaboration.
AB  - In 2010 Dillard University and Louisiana State University Health Sciences Center
      in New Orleans collaborated to secure a five year-grant from the National
      Institute of Minority Health and Health Disparities of the National Institutes of
      Health to establish a Minority Health and Health Disparities Research Center
      (MHHDRC) located on the campus of Dillard University. The MHHDRC is the first
      Federally funded Center of Excellence in the state of Louisiana. Three cores of
      the Center operate to achieve its mission. One core includes a clinical research
      associate (CRA) training program. The major goal of the program is to increase
      the number of minority CRAs in the state of Louisiana, especially in New Orleans
      and, ultimately promote greater participation and retention of minorities in
      clinical trials research. This article discusses the initiation of the CRA
      training program, its planning, community outreach, implementation, integration
      of multiple resources and role of collaboration in the development of the MHHDRC
      including accomplishments, challenges and future plans.

PMID- 24303585
TI  - ["Now go and play in a pedagogically valuable way"].

PMID- 24303586
TI  - [Personnel key in neonatology: understaffing correlates with the rate of
      nosocomial infections].

PMID- 24303587
TI  - [Photodocumentation in wound management].

PMID- 24303588
TI  - [Delegation and substitution in general and pediatric nursing - is the nurse
      liable for physician care measures?].

PMID- 24303589
TI  - [Astronaut training for children].

PMID- 24303590
TI  - [Nursing from the heart].

PMID- 24303591
TI  - [Psychological health at the work site for managers and subordinates].

PMID- 24303592
TI  - [Mother Teresa - controversial angel of the poor].

PMID- 24303593
TI  - ["Prematurity risk factor: recognizing and treating developmental risks"
      (interview by Hardy-Thorsten Panknin)].

PMID- 24303594
TI  - [Thromboembolisms in childhood and adolescence].

PMID- 24303595
TI  - [Children should be better protected against vomiting - diarrhea and influenza].

PMID- 24303596
TI  - The path to best care.

PMID- 24303597
TI  - Report from AmSECT's International Consortium for Evidence-Based Perfusion:
      American Society of Extracorporeal Technology Standards and Guidelines for
      Perfusion Practice: 2013.
AB  - One of the roles of a professional society is to develop standards and guidelines
      of practice as an instrument to guide safe and effective patient care. The
      American Society of Extracorporeal Technology (AmSECT) first published its
      Essentials for Perfusion Practice, Clinical Function: Conduct of Extracorporeal
      Circulation in 1993. The International Consortium for Evidence-Based Perfusion
      (ICEBP), a committee within AmSECT, was tasked with updating this document in
      2010. The aim of this report is to describe the method of development and content
      of AmSECT's new professional standards and guidelines. The ICEBP committee
      independently evaluated and provided input regarding the current "Essentials and
      Guidelines." Structural changes were made to the entire document, and a draft
      document was developed, presented, and circulated to the AmSECT Board of
      Directors and broader membership for comment. Informed by these reviews, a
      revised document was then presented to the Society for a membership vote. The
      final document consists of 15 areas of practice covered by 50 Standards and 38
      Guidelines (see Appendix 1) with the first standard focusing on the development
      of institutional protocols to support their implementation and use. A majority of
      the membership voted to accept the document (81.2% of the voting membership
      accepting, 18.8% rejecting). After an audit of the balloting process by AmSECT's
      Ethics Committee, the results were reported to the membership and the document
      was officially adopted on July 24, 2013. The Standards and Guidelines will serve
      as a useful guide for cardiac surgical teams that wish to develop institution
      specific standards and guidelines to improve the reliability, safety, and
      effectiveness of adult cardiopulmonary bypass. The ICEBP recognizes that the
      development of a Standards and Guidelines statement alone will not change care.
      Safe, reliable, and effective care will be best served through the development
      and implementation of institutional protocols based on these standards. AmSECT's
      Standards and Guidelines for Perfusion Practice reflect the changing landscape of
      our profession as we work toward a safer and optimal provision of cardiopulmonary
      bypass for all our patients as well as a work environment that is supportive of
      delivering this care. KEYWORDS: standards, guidelines, cardiopulmonary bypass,
      perfusion, cardiac surgery.

PMID- 24303598
TI  - Prescriptive patient extracorporeal circuit and oxygenator sizing reduces
      hemodilution and allogeneic blood product transfusion during adult cardiac
      surgery.
AB  - The goal of this cardiopulmonary bypass (CPB) quality improvement initiative was
      to maximize hemoglobin nadir concentration by minimizing hemodilution and, in
      turn, eliminating allogeneic blood product transfusion. The effects of
      transitioning from "one-size-fits-all" to "right-sized" oxygenators, reservoirs,
      and arterial-venous tubing loops were evaluated through a 2-year retrospective
      review of 3852 patient perfusion records. Using a sizing algorithm, derived from
      manufacturers' recommendations, we were able to create individualized "right
      sized" extracorporeal circuits based on patient body surface area, cardiac index,
      and target blood flows. Use of this algorithm led to an increase in the percent
      of algorithm-recommended smaller oxygenators being used from 39% to 63% (p < .01)
      and an increase in average hemoglobin nadir from 8.38 to 8.76 g/dL (p < .01).
      Decreased priming volumes led to increased hemoglobin nadir and decreases in
      allogeneic blood transfusion (p = .048). Patients with similar body surface areas
      who previously were exposed to larger oxygenators, reservoirs, and arterial
      venous loops were now supported with smaller circuits as a result of the use of
      the right-sized algorithm. Adjustments to the algorithm were made for unique
      patients and procedural situations including age, gender, and length and type of
      procedure. Larger heat exchanger surface area oxygenators were used for
      circulatory arrest procedures as a result of the need for increased heat exchange
      capability. Despite the generally higher costs of smaller circuits, reduced
      transfusion-related expenditures and decreased exposure risks justify the use of
      smaller circuit components. This quality improvement initiative demonstrated that
      as an integral part of a multidisciplinary, multimodal blood conservation effort,
      the use of the "right-sized" circuit algorithm can help to elevate hemoglobin
      nadir during CPB and eliminate allogeneic blood transfusions to patients
      undergoing CPB. KEYWORDS: cardiopulmonary bypass, oxygenator, perfusion index,
      extracorporeal circuit, hemodilution.

PMID- 24303599
TI  - Women in perfusion: a survey of North American female perfusionists.
AB  - Perfusion as a career has long been dominated by men (American Board of
      Cardiovascular Perfusion, Booklet of information since 1975). Women represent
      33.3% of the present workforce in North America (1187 certified women). In the
      1900s, fewer than 20% of women participated in the labor force compared with 75%
      today and growing (1). In addition women make only 77 cents for every dollar that
      men earn and the more education a woman has, the greater the disparity in her
      wages (2). Only 53% of employers provide at least some replacement pay during
      periods of maternity leave (2). The purpose of this survey was to poll women in
      perfusion to evaluate concerns and opinions in their careers and to compare this
      with the female labor force. In October 2011, a 40-question survey
      (surveymonkey.com) was made available to all female perfusionists in North
      American by postcard mailing through the American Board of Cardiovascular
      Perfusion. There were 538 responses to the survey, which is 45% of all female
      certified perfusionists in North America. A total of 32.6% of the survey
      participants have been in perfusion for more than 20 years and 75% are staff
      perfusionists, working for a hospital (59.5%) rather than a contract group
      (36.7%). A total of 44.7% of women who had children during their employment were
      out on leave 10 weeks or less. A total of 95.9% feel they miss important family
      functions as a result of their work schedules and 63% consider themselves under
      moderate stress. Direct supervision of the participants by men occurred in 76.5%
      of cases, and 68.2% felt that they were treated with the same respect as male
      coworkers. Nonetheless, 50.9% felt discriminated against because of gender. This
      survey suggests that the female perfusionists in North America share the same
      difficulties as women in the labor force. The role of women in society in general
      is clearly changing. Female perfusionists will be part of that change. Seventy
      percent of those surveyed would recommend perfusion as a career to both men and
      women. KEYWORDS: women, workforce, discrimination, perfusion.

PMID- 24303600
TI  - Emergent cardiopulmonary bypass for a 180 kilogram patient: support with a single
      oxygenator.
AB  - As obesity increases in prevalence, so will cases in which patients present at
      the boundaries of care. We report the support of a class III obese man, having a
      body mass index of 60.8 kg/m2 and in acute renal failure, with a single Trillium
      coated Affinity NT Hollow Fiber oxygenator in cardiopulmonary bypass for an
      emergent aortic valve replacement secondary to infective endocarditis. A maximum
      oxygen delivery of 807.51 mL of oxygen per minute is reported for this oxygenator
      in this case report.

PMID- 24303601
TI  - Regional variation in arterial saturation and oxygen delivery during venoarterial
      extracorporeal membrane oxygenation.
AB  - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be lifesaving in
      patients with cardiopulmonary collapse. However, observation studies have implied
      that oxygenated blood does not pass in a retrograde fashion from the VA-ECMO
      circuit to the aortic root and arch when the femoral artery (FA) is used. This
      study aims at accurately measuring the oxygen saturation in various arteries
      during VA-ECMO through different cannula sites. A total of 20 patients with VA
      ECMO were in the study. Fourteen patients had FA cannulation, two patients
      received axillary arterial (AA) cannulation, and four patients received
      cannulation of the ascending aorta. Oxygen saturation was measured simultaneously
      in the radial artery and oxygenator outlet. In the patient group with FA
      cannulation, the oxygen saturation was lower in the radial artery (97%) when
      compared with the oxygenator outlet (> 99%). In the subset group of patients with
      severe lung dysfunction, oxygen saturation was even lower in the radial artery
      (73% saturation). In the patient group with AA cannulation, the oxygen saturation
      and partial oxygen pressure (PO2) in the oxygenator outlet and radial artery were
      similar (99% or greater). In the patient group with direct ascending aorta
      cannulation, the oxygen saturation and PO2 in the oxygenator outlet and radial
      artery were similar as well. Regional variations occur in the blood oxygen
      saturation depending on the site of the arterial cannulation in patients with VA
      ECMO. With FA cannulation, the oxygen saturation in the radial artery is
      significantly lower than the one in the oxygenator outlet. This may imply that
      the coronaries and the brain receive hypoxic blood from the left ventricle. These
      results suggest that antegrade cannulation for VA-ECMO improves oxygen delivery
      to the proximal aorta distribution. KEYWORDS: VA-ECMO, arterial oxygen
      saturation.

PMID- 24303602
TI  - Regional perfusion during venoarterial extracorporeal membrane oxygenation: a
      case report and educational modules on the concept of dual circulations.
AB  - A challenging aspect of managing patients on venoarterial extracorporeal membrane
      oxygenation (V-A ECMO) is a thorough understanding of the relationship between
      oxygenated blood from the ECMO circuit and blood being pumped from the patient's
      native heart. We present an adult V-A ECMO case report, which illustrates a
      unique encounter with the concept of "dual circulations." Despite blood gases
      from the ECMO arterial line showing respiratory acidosis, this patient with
      cardiogenic shock demonstrated regional respiratory alkalosis when blood was
      sampled from the right radial arterial line. In response, a sample was obtained
      from the left radial arterial line, which mimicked the ECMO arterial blood but
      was dramatically different from the blood sampled from the right radial arterial
      line. A retrospective analysis of patient data revealed that the mismatch of
      blood gas values in this patient corresponded to an increased pulse pressure.
      Having three arterial blood sampling sites and data on the patient's pulse
      pressure provided a dynamic view of blood mixing and guided proper management,
      which contributed to a successful patient outcome that otherwise may not have
      occurred. As a result of this unique encounter, we created and distributed
      graphics representing the concept of "dual circulations" to facilitate the
      education of ECMO specialists at our institution. KEYWORDS: ECMO, education,
      cardiopulmonary bypass, cannulation.

PMID- 24303603
TI  - Mean arterial blood pressure during cardiopulmonary bypass.

PMID- 24303605
TI  - Inclusion of students with disabilities in the lab.

PMID- 24303606
TI  - APS asks Wildlife Service to continue chimpanzee research.

PMID- 24303604
TI  - The efficacy and safety of a pharmacologic protocol for maintaining coronary
      artery bypass patients at a higher mean arterial pressure during cardiopulmonary
      bypass. 1998.

PMID- 24303607
TI  - Italian scientists urge research restrictions be rejected.

PMID- 24303608
TI  - "Devotion to patients should not come from nurses alone".

PMID- 24303609
TI  - Nurses warn of rising pressure.

PMID- 24303610
TI  - "Most of the change needed to boost care doesn't cost a penny".

PMID- 24303611
TI  - "Practical skills must be taught to ensure compassionate care".

PMID- 24303612
TI  - Long-term central venous access device selection.
AB  - Infusion therapy is often viewed as a means to an end - a way to administer
      medications and fluids. It is one of the few specialties that affect almost all
      areas of healthcare. Safe, effective and reliable vascular access should be the
      goal of every health professional who is starting a patient on a prescribed
      course of intravenous therapy, especially if that patient is undergoing a
      prolonged course. This article aims to refresh and update nurses' clinical
      knowledge of the detailed patient assessment required before choosing a central
      venous access device, as well as supporting a reduction in complications and
      earlier recognition of potential problems. It discusses clinical indications for
      devices, the range of long-term intravenous therapies that can be used, and
      patient assessment.

PMID- 24303613
TI  - Nausea and vomiting in palliative care.
AB  - Nausea and vomiting in patients with advanced disease are debilitating symptoms
      that reduce the quality of life for patients, their families and carers. These
      symptoms are common in patients with both malignant and non-malignant disease.
      Palliative care intervention has been shown to improve them significantly,
      thereby improving patient experience of end-of-life care. This article discusses
      systematic and thorough assessment of patients to identify possible causes, and
      how these can be corrected where possible. Simple measures to manage symptoms can
      be effective in improving nausea and vomiting without the need for medication,
      and these should be considered in the first instance. We give also explain the
      pathophysiology of nausea, including the neurotransmitters involved, to help
      guide appropriate prescribing.

PMID- 24303614
TI  - Sharing nutrition needs from care home to ward.

PMID- 24303615
TI  - A hospital nutrition improvement programme.
AB  - Healthcare Improvement Scotland (formerly NHS Quality Improvement Scotland) led
      an 18-month national programme that aimed to achieve reliable improvements in
      nutritional care by focusing on three priority areas: mealtimes; long-term
      conditions; and transition to care homes.

PMID- 24303616
TI  - 60 seconds with Anne Nash.

PMID- 24303617
TI  - Joint work eases joint pain.

PMID- 24303618
TI  - Mindfulness can make work run more smoothly.

PMID- 24303619
TI  - Patient's page. Keeping your child's teeth healthy begins early.

PMID- 24303620
TI  - Realities from the road: Bixby and Glenpool.

PMID- 24303621
TI  - Affordable Care Act and oral health: ADA analysis of impact.

PMID- 24303622
TI  - Paperless by 2014?

PMID- 24303623
TI  - Ethicsese.

PMID- 24303624
TI  - Finding a cure for violence.

PMID- 24303625
TI  - Why coverage counts.

PMID- 24303626
TI  - Is Texas an exception?

PMID- 24303627
TI  - Taking credit. Moody's: Medicare reimbursement rates affecting hospital credit.

PMID- 24303628
TI  - Separately together. Systems work jointly on managing population health.

PMID- 24303629
TI  - Auditable use. Meaningful use audits trip up some hospitals.

PMID- 24303630
TI  - Telemedicine:'If you aren't doing anything now, you're way behind'.
AB  - Any health care provider that's not taking advantange of the many advances in
      audiovisual tools to connect with patients is woefully behind the curve, experts
      warn. Here's what some hospitals are up to in both rural communities and urban
      areas.

PMID- 24303631
TI  - Growing need for HIT talent.

PMID- 24303632
TI  - Revisiting e-visits. Electronic visits slow to be embraced by payers and
      providers.

PMID- 24303633
TI  - Retail clinics: threat or opportunity?
AB  - The explosion of retail clinics worries some traditional health care providers.
      But clinic leaders say far from competing with hospitals and physicians, they're
      helping to build a care continuum.

PMID- 24303634
TI  - What big biz wants now. Interview by Matthew Weinstock.

PMID- 24303635
TI  - Engineering a fail-safe health system. Memorial Hermann wants to eliminate health
      care errors (really).
AB  - Memorial Hermann Healthcare System is on an all-out mission to eliminate health
      care-acquired infections. Despite a bit of physician resistance, the results so
      far are astonishing.

PMID- 24303636
TI  - Diabetes: the right care and the right reimbursement.
AB  - Managing patients with diabetes or other chronic diseases is suddenly a major
      focus for hospitals. They're working with insurers to develop fair, effective
      reimbursement models.

PMID- 24303637
TI  - Strategies for managing a generationally diverse workforce.

PMID- 24303638
TI  - Vivid spectacle, powerful message for teens.

PMID- 24303639
TI  - Artistry of a leader.

PMID- 24303640
TI  - A decade of change.

PMID- 24303641
TI  - Unlocking the value of medical equipment.

PMID- 24303642
TI  - Risk management in radiology.
AB  - Recent US nationwide research on malpractice lawsuits shows that the most common
      cause of medical malpractice suits against radiologists was error in diagnosis
      (mainly failure to diagnose instead of delay); the category next in frequency was
      procedural complications, followed by inadequate communication with either
      patient or referring physician. Risk management is a fundamental instrument to
      prevent and limit errors and adverse events. This article analyzes risk
      management in radiology addressing the most common ethical-legal issues on
      appropriateness of prescriptions, informed consent, and management of adverse
      events. Effective remedial actions are proposed to avoid malpractice claims that
      would help physicians in preventing malpractice stress syndrome, leading to
      defensive medicine.

PMID- 24303643
TI  - Support your boss.

PMID- 24303644
TI  - The cost of doing business in academic radiology departments.
AB  - This study identifies the major sources of overhead fees/costs and subsidies in
      academic radiology departments (ARDs) in the US and determines the differences
      between them based on geographic location or the size of their affiliated
      hospital. ARDs in the Northeast had the highest level of financial support from
      their affiliated hospitals when compared to those in the South/Southwest;
      however, a greater number of Midwest ARDs receive high levels of funding for
      teaching from their medical schools when compared to the northeast. Significantly
      fewer ARDs affiliated with hospitals of less than 200 beds receive subsidies for
      their activities when compared to those affiliated with larger hospitals.
      Differences in levels of overhead costs/ subsidies available to ARDs are
      associated with either geographic location or the size of the affiliated
      hospital. The reasons for these differences may be related to a variety of legal,
      contractual, or fiscal factors. Investigation of existing geographic and
      affiliate size fiscal differences and their causes by ARDs may be of benefit.

PMID- 24303645
TI  - ICD-10: 2014 updates.

PMID- 24303646
TI  - ICD-10: an opportunity and a challenge.
AB  - This article provides a high level summary of ICD-10 implementation to ensure
      imaging leaders are ready for this monumental shift in the healthcare industry.
      Although it will be challenging, there are a number of compelling reasons for the
      change. It is important to remember that ICD-10-CM is not just a software update
      or something that only coders have to worry about. Scheduling and registration
      staff, clinicians, billing staff, and edit/denials department will all be
      affected. For radiology services, the biggest area impacted is trauma. The
      majority of the implementation planning will be outside of your control, but you
      should get involved where you can. Identify the items that are unique to
      radiology and make your own plan to ensure they don't get overlooked. The first
      thing to do is select a champion.

PMID- 24303647
TI  - No ifs, ands, or buts.

PMID- 24303648
TI  - Reducing anxiety in pediatric patients.
AB  - Staff at St. Joseph's Children's Hospital, an acute care comprehensive state
      designated children's hospital located at St. Joseph's Regional Medical Center in
      Paterson, NJ developed media products to prepare children and their parents for
      the imaging environment. Pediatric patients-especially those between the ages of
      two and ten-became anxious and worrisome upon entering the imaging room. Five
      videos would be produced: one each for parents and pediatric patients for both x
      ray and MRI, as well as one targeted for imaging staff. Video segments lessened
      anxiety, enabled greater cooperation, and helped get the optimal images on the
      first attempt. Positive feedback has supported this and contributed to greater
      patient satisfaction.

PMID- 24303649
TI  - Ten steps to being productive.

PMID- 24303650
TI  - The importance of passing it on.

PMID- 24303652
TI  - [Epidemiological profile, clinical and therapeutic cutaneous leishmaniasis in the
      Department of Dermatology at University Hospital in Ouagadougou, Burkina Faso].
AB  - It is a retrospective study in the Service of Dermatology at the University
      Hospital Center Yalgado Ouedraogo of Ouagadougou (C.H.U.-YO). This study aimed to
      list the leishmaniasis clinical cases reported in the registers of this
      department from January 1999 to December 2007. In total, 251 leishmaniasis
      clinical cases have been reported. The hospital prevalence was 1,1%. Women
      represented 53% versus 47% men. The average age of patients was 22,78 ans +/-
      121. The most frequent clinical forms were those often crusted (40.2%), papulo
      ulcerative (16.7%) and papulonodular (13.9%). Lesions most often sat on the lower
      limbs (33%) and thoracic limbs (45%). On the therapeutic level, the first line
      treatment meglumine antimonite (Glucantime) accounted for only 25.9% of
      prescriptions.

PMID- 24303653
TI  - [Is ovarian function impaired in HIV patients? A clinical pilot study in Burkina
      Faso].
AB  - A lot of studies published on the ten last years showed a decrease of fertility
      among HIV positive women. The present research aims to see if this decrease is
      linked to an ovarian failure, using AMH as principal marker of ovarian function.
      In this pilot study, 54 HIV-positive and 39 HIV-negative women were compared on
      the basis of their ovarian function, fecundity and possible ovarian failure. A
      blood sample was taken for hormonal titrations, HIV seropositivity, viral load
      and CD4 T cell count. An interview explored demographic characteristics,
      obstetrical and infectious history, and menstrual characteristics. This study was
      performed in Burkina Faso between January and February 2008. There is no
      significant difference after adjusting for age of AMH level between the two
      groups. However, in our study, 5.5% of HIV positive women had a premature
      menopause, which is a significant variation from the premature menopause rates of
      the African population, which is 1.4%. In conclusion, this study put the HIV
      impact on ovarian function into perspective but the high premature menopause
      rates could suggest an ovarian attack by the virus or the treatment.

PMID- 24303654
TI  - [Prospective study of waiting time delays in a university hospital emergency
      department with a physician triage model].
AB  - To measure waiting time delays of patients and to evaluate if the waiting time
      before the first physician contact is inversely correlated to the illness
      severity. During the period of 26/02/2007 through 3/03/2007, we prospectively
      studied the waiting times before the first contact with a physician (WTP) and the
      length of stay (LS) in 473 patients (0.8% of the annual patient volume) evaluated
      in our emergency department, which has a physician triage model. The WTP was
      correlated to a severity score "Clinical Classification of Patients in Emergency
      (CCPE)". The median WTP was: 48 (22-79) min. (minutes) (median, P25, P75). This
      time was 33 (14-47), 16 (3-28) and 3 (0-3) min. for patients having a CCPE score
      of 3, 4 and 5. The median LS was 119 (76-186) min. In conclusion, the waiting
      times are comparable to those measured in similar studies. The waiting time
      evaluated according to CCPE is adequate.

PMID- 24303655
TI  - [Management of acute iliac thrombosis in a pregnancy at term: case discussion and
      review of literature].
AB  - Venous thromboembolic disease during pregnancy is an important cause of obstetric
      morbidity and mortality. Suggestive clinical signs lead systematically physicians
      to evocate this diagnosis. Unfortunately, the incidence of events remains low,
      reducing the ability to perform well-designed research and to give adequate
      recommendations. The discovery in term pregnancy of an iliofemoral venous
      thrombosis raises the question of obstetrical care, mainly considering
      potentially embolic risk. Through a case report and based on a thinking about the
      few medical publications in this field, we suggest that the placing of temporary
      inferior vena cava filter in presence of an extensive deep venous thrombosis at
      term pregnancy could be debatable.

PMID- 24303656
TI  - [Treatment of depression with transcranial magnetic stimulation].
AB  - Major depression disorder is a frequent psychiatric condition with serious
      consequences. Many patients don't respond to usual psychopharmacological and/or
      psychotherapeutic treatments. This observation has stimulated the research of
      alternative treatment options. Repeated transcranial magnetic stimulation (rTMS)
      is a recent therapeutic tool with few side effects. Its efficacy relies on
      stimulation of cortical networks through the application of a magnetic field on
      the skull. rTMS has been approved as a full therapeutic option for major
      depressive disorder by the FDA in 2008. It could therefore be routinely used in
      the future and complete the usual treatments in this condition. Our paper reviews
      what is currently known about the clinical use of rTMS in major depressive
      disorder.

PMID- 24303657
TI  - [Use of extraoral implants for nasal rehabilitation with epithesis after
      carcinologic surgery. A case report].
AB  - Maxillofacial defect caused by cancer treatment represents a problem affecting
      the quality of life of patients. Epithethic solutions are indicated if plastic
      surgery reconstruction is not a valid option for an extensive defect. We present
      the case of a 42 years-old woman, who had undergone a total nasal resection, for
      a well-differentiated epidermoid carcinoma of the tip of the nose. The
      anatomopathologic analysis of the piece of resection showed free margins, and did
      not reveal any ganglionar metastasis. No radiotherapy was applied. Three months
      later, four extraoral implants were placed in the frontal and paranasal areas
      with a transcutaneous approach, in order to avoid crusting resulting from trans
      nasal mucosa emergence of the fixtures. After four months, each implant as a bone
      anchorage was connected with a prosthetic retention device to be connected to the
      nasal epithese. After four weeks, cutaneous healing allowed the prosthetic steps
      to be achieved. The use of extraoral fixtures as bone anchorage for a nasal
      epithesis represents an alternative to more heavy and time-consuming surgical
      reconstruction techniques. Another advantage is that the site can be monitored
      easily because the epithesis is removable, as for the carcinologic follow-up. It
      allows a good retention of the nasal epithesis and an esthetic result which is
      satisfying for the patient.

PMID- 24303658
TI  - [Hyperostosis frontalis interna and epilepsy].
AB  - We have analysed the clinical history of a 48-year old female patient who has
      been admitted to hospital after an epileptic fit. The tomodensitometry
      examination has shown a hyperostosis frontalis interna. This condition is
      frequent and is characterized by a progressive thickening of the frontal bone
      internal table. The aetiology is unknown; the most probable hypothesis is a
      deterioration of the androgen-estrogen ratio. This woman suffers from epileptic
      fits for 40 years now but also from hereditary polycystic kidney disease and
      CREST syndrome. In this analysis, we have applied the principle of parcimony and
      we have examined the role played by the sexual hormones in these pathologies.

PMID- 24303659
TI  - [Foreign body aspiration in Kigali University Teaching Hospital, Rwanda].
AB  - We present the case of a 12-year-old girl referred to Kigali University Teaching
      Hospital (KUTH) for persistent cough, fever and haemoptysis. Respiratory symptoms
      started acutely with a stridor at age 4. Thereafter she developed a chronic cough
      with intermittent fever. She was treated ambulatory in the health care centre
      with oral antibiotics and finally referred to the district hospital at age 7. The
      chest X-ray then suggested tuberculosis for which a 6 month treatment was given
      with no improvement. The cough persisted and haemoptysis appeared so the patient
      was referred to the reference hospital (KUTH). Chest X-ray showed diffuse lesions
      of the left lung with bronchiectasis. Bronchoscopy revealed the presence of a
      foreign body in the left intermediary bronchus and a piece of plastic was
      extracted. Symptoms rapidly disappeared with antibiotic treatment. This case
      illustrates how important it is to include foreign body inhalation in the
      differential diagnosis of respiratory disease in children. Bronchoscopy plays a
      key role in diagnosis and treatment. The authors point out the advantages of the
      joint efforts of the Belgian Development Aid Agency (BTC) and the Universite
      libre de Bruxelles (ULB) in the development of this activity in the Rwandese
      context.

PMID- 24303660
TI  - [Alcoholism around the turn of the 20th century: the Belgian positions in
      European debates].
AB  - In Europe, between 1880 and 1914, the alcoolism, one of the three social ills,
      represents more than ever a concern among the society's leaders against the
      ravages it causes in their working class. In this context, two schools of "anti
      alcoholism" clash to policy matters: to prevent to only spirits or any form of
      alcohol beverage. Belgium, land of beer, forms an integral part of the debate...

PMID- 24303661
TI  - [Thoracic Oncology 14th annual meeting].

PMID- 24303662
TI  - [An end to violence against nurses!].

PMID- 24303663
TI  - [National health strategy finally revealed].

PMID- 24303664
TI  - [Proposals for a new health democracy in institutions].
AB  - Dignity, or rather a lack thereof, in healthcare institutions, often becomes
      apparent through a situation where the patient, or sometimes the nurse, is not
      given due respect. It is important to promote a real democratic culture, an
      authentic collective dialogue. This article presents the basis of a fundamental
      notion.

PMID- 24303665
TI  - [The approach to dignity].
AB  - The notion of dignity evokes what touches humans most deeply. Through the ages,
      it has been considered from different perspectives. Doctors, philosophers and
      specialists in ethics have expressed themselves on its purpose. This article
      looks at an essential definition based around care.

PMID- 24303666
TI  - [Admission to the emergency department and dignity].
AB  - A restructuring of the emergency department of Kremlin Bicetre University
      Hospital presented an opportunity for a multi-disciplinary discussion to consider
      new nursing practices. As a result, people admitted to the emergency department
      can benefit from greater privacy and maintain their dignity despite the "usual
      saturation" of the department.

PMID- 24303667
TI  - [Dignity in nursing homes].
AB  - It is by taking vulnerable people into account that a civilisation can prove
      itself worthy of this name, as elderly people can testify. These vulnerable
      people are thereby placed at the centre of public healthcare plans. What is the
      situation in nursing homes and what needs to be done to give them as much dignity
      as possible in all circumstances?

PMID- 24303668
TI  - [The end-of-life law and possible future developments].
AB  - What is the situation today regarding end-of-life care in France? Is it
      sufficiently understood by the general public and professionals? While a series
      of legislative measures exists, it appears that most people have insufficient or
      no knowledge of them. This article presents an overview of the current situation
      and considers the future perspectives.

PMID- 24303669
TI  - [A nursing career guided by a keen interest in emergency care].
AB  - Aymeric Lapp has been a state-registered nurse for ten years. Particularly
      interested in emergency care and procedures, in this article he shares the
      highlights of his career, exploring the different sides of a profession whose
      practices he now enjoys teaching to others.

PMID- 24303670
TI  - [Audit of implantable port practices at home].
AB  - In oncology, treatments very often require the use of implantable ports to
      administer drugs, either at hospital or at home. In order to gain a better
      understanding of the specific problems encountered at home, the teams of the Paul
      Papin Oncology Institute in Angers carried out an audit of the protocols and
      conditions regarding the use of these medical devices at home, to improve safety.

PMID- 24303671
TI  - [Woongroepen, an original way of caring for elderly people].
AB  - A group of eleven third-year students and two trainers from the Nancy nurse
      training institute visited the Netherlands in the framework of an optional unit
      focusing on European approaches in nursing studies. During their stay, they
      discovered an original type of collective accommodation, called woongroep, which
      helps to improve elderly people's quality of life.

PMID- 24303672
TI  - [The cultural barrier in care].
AB  - French cultural diversity is evident within French hospitals, where nurses are
      confronted with communication problems resulting from the language barrier. While
      communication is indeed essential, there is another important aspect of caring
      for a patient for behind the language barrier lies a cultural barrier which must
      be taken into account in order to provide high-quality care.

PMID- 24303673
TI  - [Identifying domestic abuse in an emergency department].
AB  - Domestic violence is a public healthcare problem. A woman dies every two and a
      half days at the hands of a violent partner. An emergency department has set up a
      service comprising an interview with a nurse especially trained in identifying
      and helping victims of domestic abuse.

PMID- 24303674
TI  - [A communication tool adapted to English-speaking patients].
AB  - Rouen university hospital cares for increasing numbers of non-French-speaking
      patients: tourists, patients from the Mediterranean basin, Eastern Europe, etc.
      To optimise this care, a communication tool was developed in 2012 to be used with
      English-speaking patients.

PMID- 24303675
TI  - Children's infectious diseases.

PMID- 24303676
TI  - [Nursing care of agitation].

PMID- 24303677
TI  - [Nutrition and hypercholesterolemia].

PMID- 24303678
TI  - [Nursing training of radiology].

PMID- 24303679
TI  - [Endotracheal aspiration].

PMID- 24303680
TI  - A closer look at the two-midnight rule, what it means for ED providers.

PMID- 24303681
TI  - [Unusual ultrasound presentation in gallbladder diseases].

PMID- 24303682
TI  - [Esophageal polypoid lesion].

PMID- 24303683
TI  - [Guillaume Dupuytren].

PMID- 24303684
TI  - [Utility of routine gastric biopsies and staining with methylene blue in the
      diagnosis of intestinal metaplasia in patients over 40 years].
AB  - OBJECTIVE: To evaluate the diagnostic utility of routine gastric biopsies taken
      at random versus targeted biopsies with methylene blue staining for the diagnosis
      of intestinal metaplasia. MATERIAL AND METHODS: We performed a validation study
      in 376 patients. We performed 2 antral biopsies, 2 gastric body biopsies, 1
      biopsy for urease test and additional biopsies if demanded. One hundred and one
      patients underwent 2 biopsies after methylene blue staining. A total of 1,486
      biopsies were analyzed. Frequencies of histological and endoscopic diagnosis and
      the validation of endoscopic diagnosis of intestinal metaplasia with and without
      staining against histology, which followed updated Sydney and Vienna criteria,
      were determined RESULTS: Metaplasia was found in 37.23% ofcases and in 6.38% was
      incomplete in antrum and body, moderate or severe. The endoscopic diagnosis had:
      sensitivity 46%, specificity 91%, positive predictive value (PPV) 75% and
      negative predictive value (NPV) 74%. The low sensitivity indicates the need for
      gastric biopsies. Staining had: sensitivity 95%, specificity 67%, PPV 84% and NPV
      89%, with significant difference for staining (P < 0.05). The typical endoscopic
      appearance of intestinal metaplasia always coincided with staining and histology.
      Dysplasia was found in 0.53% ofcases, gastric cancer in 1.8% and Helicobacter
      pylori in 56%. CONCLUSION: Directed biopsy staining is superior to those taken at
      random for diagnosing metaplasia. Metaplasia was not found when endoscopy was
      normal and typical endoscopic appearance of metaplasia agreed with staining and
      histology.

PMID- 24303685
TI  - [Relevance of an adequate pathologic evaluation of radical rectal resection
      specimens].
AB  - BACKGROUND: The most important prognostic factors influencing survival of
      patients with rectal carcinoma (RC) are lymph node metastases and mesorectal
      excision (ME). The adequate pathologic examination (APE) of rectal specimens is a
      standardized pathologic work-up that differs of the conventional
      colonic/intestinal pathologic work-up. The aim of this study was to determine the
      impact of APE on staging, lymph node retrieval and survival, with the hypotheses
      that APE allows high lymph node retrieval and better survival. METHODS: We
      retrospectively analyzed patient with surgery for RC from 2004 to 2011. We
      described the APE of radical rectal resection and we compared the clinical and
      pathological characteristics and the oncologic results, including survival after
      and before APE. RESULTS: A total of 185 patients were evaluated, 114 constituted
      the pre-APE group and 71 the APE group. The mean lymph node retrieval was 13.7 in
      the pre-APE group and 19.6 in the APE group (P = 0.007). In the APE group we
      found less local recurrence (20% vs 34%, P = 0.024), more lymph-vascular invasion
      (20% vs 5%, P = 0.003), higher prevalence of high grade tumors (20% vs 4%, P =
      0.001), more alive patients free of disease (75% vs 49%, P = 0.001), more
      frequent use of neoadjuvant therapy (58% vs 31%, P = 0.001), and and better 4
      year survival (78% vs 53%, P = 0.044). CONCLU- SION: The APE is crucial in
      patients with RC for staging and planning further treatment. An APE added to
      neoadjuvant or adjuvant therapy was associated with better survival.

PMID- 24303686
TI  - [Relationship between dietary glycemic index and glycemic load and nonalcoholic
      fatty liver disease in elderly].
AB  - OBJECTIVE: To investigate if there is an association between glycemic index (GI)
      and glycemic load (GL) of the diet and the presence of nonalcoholic fatty liver
      disease (NAFLD) in the elderly. METHODS: Retrospective study, composed of 229
      patients seen at the Outpatient Clinic of Arterial Hyperten- sion in a public
      hospital, 103 carriers and 126 noncarriers of NAFLD. Food intake was analyzed to
      GI and GL. RESULTS: We found a high prevalence of inadequate dietary GI, with an
      average of 62.0 +/- 6.3 among patients with NAFLD and 62.5 +/- 6.5 among patients
      without NAFLD. The same occurred with the GL, 101.7 +/- 33.3 and 101.4 +/- 40.2,
      respectively, between carriers and noncarriers of the disease. There was no
      statistical difference between the values of GI and GL found in the diet of
      patients with and without NAFLD. CONCLUSION: In the evaluated group there was no
      association between GI and GL dietetic with NAFLD, but the findings put all of
      the patients at higher risk for the development of chronic diseases.

PMID- 24303687
TI  - [A study on hepatic iron overload in chronic hepatitis C patients].
AB  - BACKGROUND: Hepatitis C is a worldwide chronic liver disease. Different factors
      have been found to be associated with an increased progression to severe liver
      fibrosis, such as alcohol intake higher than 30 g/day, older age at infection and
      co-infection. Nevertheless, different research centers have found conflicting
      data concerning the liver iron overload fibrogenic role. AIM: To assess the
      association between hepatic iron overload and fibrosis stage grades in hepatitis
      C Virus carriers, hepatic steatosis and demographic variables. METHODS: In this
      descriptive study we recruited 290 positive anti-HCV and qualitative HCV-RNA,
      treatment naive chronic hepatitis C outpatients registered fom 2007 to 2009 at
      the Federal University of Bahia's Hospital. The variables studied in the liver
      biopsy results were: 1) fibrosis stage according to META VIR score (F0-F4), 2)
      iron overload presence or absence according to Perls staining, and 3) presence or
      absence of steatosis. Fibrosis stages were categorized as mild/moderate (F0-F2)
      and severe (F3-F4). Exclusion criteria were hepatitis B virus and human
      immunodeficiency virus co-infection, and primary or secondary hemochromatosis.
      The statistical analysis was performed using Chi-square and Student's t tests,
      with the ssoftware: SPSS 17. A P value < 0.05 was considered as significant.
      RESULTS: Severe fibrosis was statistically associated with older age, iron
      overload presence (P = 0.003) and steatosis (P = 0.01). CONCLUSIONS: In this
      study hepatic iron overload and hepatic steatosis were associated with severe
      hepatic fibrosis (METAVIR F3-F4).

PMID- 24303688
TI  - [Comparison of strength of the handshake with anthropometric and subjective
      parameters at the patients' nutritional assessment with liver diseas].
AB  - OBJECTIVE: We aimed to assess the nutritional status of patients with chronic
      liver disease by evaluating the strength of grip of non-dominant hand (SGNDH),
      correlating it with other methods and analyzing their contribution to this
      assessment. METHODS: This study was conducted with patients having chronic
      chronic disease at the outpatient hepatology service of the Instituto de Medicina
      Integral Professor Fernando Figueira--IMIP, Recife-PE, from February to October
      2010. Clinical and demographic variables were collected. The evaluation was
      performed according to anthropometric, subjective and functional parameters.
      RESULTS: There were evaluated 49 individuals and 65.3% of them were men. The mean
      age was 51.3 years and individuals over 60 year predominated. The patients
      presented non-alcoholic liver disease in 61.2% of cases, MELD < or = 10 in 67.3%,
      some gastroenteropathy in 67.4%, jaundice in 66.7% and ascites in 63%. The global
      average SGNDH was higher among men with higher prevalence of malnutrition by arm
      muscle area (AMA), followed by arm muscle circumference (AMC) and SGNDH, and
      lower prevalence by body mass index (BMI) and adapted subjective global
      assessment (SGA). There were not statistically significant differences between
      the prevalence of malnutrition by SGNDH and arm circumference (AC), triceps
      skinfold (TS), AMC, AMA and Mendenhall score. The diagnosis of malnutrition by
      SGND was higher among men and 100% among elderly (P < 0.05). There was strong
      correlation between SGNDH and AMC, regular between SGNDU and height, and weak
      between SGDNH and AC (P < 0.05). CONCLUSIONS: It is noted that the SGNDH showed
      similar contribution than AMA and AMC and higher than BMI and adapted SGA. The
      strong correlation between SGNDH and AMC indicates a major relationship with
      muscle reserves. Thus, more studies are needed to clarify the application of
      SGNDH in this nutritional assessment. We point out that an association of
      different methods is necessary.

PMID- 24303689
TI  - Intestinal obstruction and pseudo-obstruction in patients with systemic
      sclerosis.
AB  - Chronic intestinal pseudo-obstruction is a known complication of patients with
      systemic sclerosis, manifested as nausea, vomiting, constipation, abdominal
      distension and pain. We report a series of cases with systemic sclerosis that
      presented with signs of intestinal obstruction. In all cases, the differentiation
      between a pseudo-obstruction and true mechanical obstruction remained a
      formidable challenge. Our goal was to present different scenarios of patients
      with systemic sclerosis and features of intestinal obstruction, with a review on
      its clinical approach.

PMID- 24303690
TI  - [Esophageal papilloma: case report, molecular identification of human
      papillomavirus and literature review].
AB  - sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor
      of the squamous epithelium consisting of a raised, sessile, small and round
      (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with
      a male/female ratio of 3:1. The etiology and pathogenesis appear to be a
      mechanical or chemical irritation of the mucosa in addition to the presence of
      human papillomavirus (HPV), important agent in the evolution to a squamous
      carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of
      esophageal papilloma whose diagnosis involved endoscopic images, pathological
      studies and detection of viral DNA by polymerase chain reaction. By using
      molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been
      obtained. The patient underwent polypectomy and currently, after 3 years of
      diagnosis, he remains asymptomatic. This work is one of the first national
      reports of a patient with esophageal papilloma in which one of the most
      frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been
      detected.

PMID- 24303691
TI  - [Giant Amyand hernia].
AB  - The finding of the appendix inside an hernial sac is called "Amyand hernia": The
      global incidence is 0.28 to 1%. Clinical manifestations are the presence of an
      inflamed inguinal mass, tense, hypersensitivensible, with variable size, non
      reducible, and associated to abdominal pain, vomit and very rarely true
      appendicitis manifestations. Surgical treatment depends on the case presentation
      and the intraoperative findings. We present a case of a giant Amyand's hernia
      successfully treated with surgery by performing the hernia repair with Bassini
      technique and transherniotomy appendectomy.

PMID- 24303692
TI  - Wilkie's syndrome: review of eight cases.
AB  - BACKGROUND: The superior mesenteric artery (SMA) syndrome is a rare entity
      presenting with upper gastrointestinal tract obstruction and abrupt weight loss.
      Usually seen in tall individual with low bod mass index (BMI), the weight loss
      may be primary or secondary to a systemic disease or to the syndrome itself
      Compression of the duodenum between the abdominal aorta and the superior
      mesenteric artery due to loss of the duodenal pad of fat causes the obstruction.
      Early recognition prevent complications. Imaging and endoscopy is diagnostic.
      Aorto-mesenteric angle and SMA aorta distance is lower than 22 degree and eight
      millimeter respectively. If nutritional support fails, surgery is required (e.g.
      guodeno-jejunostomy). Studies to determine the optimal methods of diagnosis and
      treatment, especially in a suburban hospitals with limited expertise are
      essential. CASE REPORT: We retrospectively evaluated 8 cases presented over three
      years. Six (75%) patients were males, age ranged from 19 to 70 years and weight
      from 40 to 55 kg. The mean BMI was 18.7 kg/ m2 (range 16.42 to 25.11 kg/m2). Mean
      weight loss before diagnosis was 9.88 kg (range 6 to 12 kg). Symptoms developed
      between 8 to 180 days (median 12 days). Commonest presentation was epigastric
      pain, vomiting and nausea. Four patients had pre-morbid conditions and the
      syndrome was idiopathic in the other 4. Median aorto-mesentric angle was 16.5
      degree and SMA-aorta distance was 5.15 mm. Four patients required operation. The
      rest improved on conservative treatment. CONCLUSION: Early recognition,
      institution of the appropriate conservative measures and timely selection of a
      definite surgical method are critical to prevent severe complications and death.

PMID- 24303693
TI  - Groove pancreatitis vs groove pancreatic adenocarcinoma. Report of two cases and
      review of the literature.
AB  - Groove pancreatitis (GP) is a rare form of segmental chronic pancreatitis
      affecting the groove area (anatomic space between the head of the pancreas, the
      duodenum and the common bile duct). Its clinical and radiological presentation
      may be similar to groove pancreatic adenocarcinoma (GPA). Nevertheless, treatment
      and prognosis are totally different. We report two cases of both GP and GPA and
      review the relevant aspects that may help to clarify the differential diagnosis
      between these two rare entities. The first patient is a 57-year-old man with a
      history of chronic alcohol consumption who presented with persistent abdominal
      pain. The CT-scan findings suggested GP. Due to the persistence of symptoms
      despite medical treatment, a pancreaticoduodenectomy was performed. Pathologic
      evaluation confirmed the diagnosis of GP. The second patient is a 72-year-old
      male who presented with cholestasis and weight loss. The tumor marker CA 19-9 was
      increased The CT-scan findings were consistent with duodenal dystrophy. In order
      to rule out malignancy a pancreaticoduodenectomy was performed. Pathologic
      evaluation revealed a pancreatic head adenocarcinoma (T3-N1-M0). GP is a rare
      entity that should be suspected in patients with a history of heavy alcohol
      consumption who complain of chronic abdominal pain and weight loss. Patients
      without a clear diagnosis even after a through imaging work-up, or those in whom
      symptoms are persistent in spite of medical therapy, should undergo surgical
      exploration.

PMID- 24303694
TI  - [Nonalcoholic fatty liver disease. A current perspective].
AB  - A review about nonalcoholic fatty liver disease is presented, considering the
      updated aspects related to pathophysiology, diagnosis and management of this
      medical condition.

PMID- 24303695
TI  - [Assessment and management of risks in the maritime sector: commercial fishing].
AB  - The activity of sea fishing involves a series of unfavorable conditions that can
      affect the health and safety of workers. The contribution presented here deepens
      the analysis of some occupational hazards such as: "ergonomics of workstations,
      manual handling of loads, awkward postures, repetitive movements of the upper
      limb". The work is based on local experience gained in the Marche region, namely
      in the ports of Ancona and San Benedetto del Tronto (75% of all marine fishing
      Marche). The assessment of these risks turn based on methodologies and NIOSH OCRA
      has led to the design and implementation of solutions to improve both
      organizational and technical. These solutions were transferred on to boats in the
      fleet Marche.

PMID- 24303696
TI  - [Asbestos related cancers in seamen].
AB  - Seamen and marine engineers were formerly exposed to asbestos used in gasket,
      pipes, valves and machinery. Ship motion and vibration can release asbestos in
      the surrounding space. Asbestos fibres may also be inhaled by workers involved in
      maintenance operations of vessels built before 1992 in Italy. History of asbestos
      exposure has been reported by workers and confirmed by a higher prevalence of
      pleural abnormalities and a significant excess of mesothelioma with a
      Standardized Incidence Ratio (SIR) ranging between 1.83 and 4.8 as a function of
      years of exposure. SIR for lung cancer ranged between 1.10 and 1.62. Mesothelioma
      in seamen and marine engineers represents about 2.5% of the overall Italian
      mesothelioma cases with a very long latency period (47.6 +/- 9.6 years). There is
      no epidemiological evidence for an excess risk of mesothelioma in fishermen.

PMID- 24303697
TI  - [WBV risk in maritime and port operators].
AB  - Whole Body Vibration (WBV) is the shaking or jolting of the human body through a
      supporting surface, usually a seat or floor. The risk from vibration is related
      to the overall time the operator or driver is exposed to the vibration and the
      number of shocks and jolts they experience each day. In the 27 countries of
      Europe the EC Physical Agents Directive, effective 6th July 2010, requires all
      employers to control exposure to a number of hazards including noise and
      vibration. The EC Vibration Directive sets out regulations for the control of
      health and safety risks from the exposure of workers to hand arm vibration (HAV)
      and whole body vibration (WBV) in the workplace. The maritime sector needs to
      comply: high exposure WBV levels can be found when operating RIBs and High Speed
      Craft. Marine sectors affected by Whole Body Vibration (WBV) include military,
      search & rescue, government agencies, local authorities, police, water sports,
      oil & gas, thrill ride, charter and all organisations operating boats, RIBs
      (Rigid Inflatable Boat) and High Speed Craft.

PMID- 24303698
TI  - [Noise in fishing vessels].
AB  - The present research concerns the noise analysis of five vessels during
      navigation and fishing activities. In locations where staff operates, sound
      levels (produced substantially by the engine) were close to 90 dB(A); within the
      rest areas the noise is also quite significant. On the basis of working time,
      exposure levels ranged between 80 and 90 dB(A). In order to identify
      interventions able to reduce the risk, reverberation times, sound insulation of
      the different areas and the vibrations produced by the engine were measured on
      the same vessels docked in port. Noise level reduction as a result of sound
      absorptive treatments were estimated using an analytical model.

PMID- 24303699
TI  - [Skin and sun exposure].
AB  - Fisherman commonly experience a significant number of cutaneous problems, related
      to the exposure to environmental factors due to their working conditions. Among
      these factors, sun exposure is able to determine both acute and chronic skin
      damage, mostly linked to the effects of the ultraviolet (UV) radiation on
      epidermal and dermal structures. In particular, UV-A appears to play a major role
      in the deterioration of dermal structure leading to the photoaged appearance of
      the skin, while UV-B is mainly responsible for skin cancers. Peculiar clinical
      features of skin damage in fishermen include dryness, irregular pigmentation,
      wrinkling, stellate pseudoscars, elastosis, inelasticity, telangiectasia,
      comedones and sebaceous hyperplasia. Furtheremore, the high incidence of non
      melanoma skin cancers, on sun-exposed areas, confirms the need for occupational
      health policies focusing on issues such as photoprotection.

PMID- 24303700
TI  - [Protocols for the health surveillance of fisherman].
AB  - AIM: To define protocols for health surveillance of workers in the marine fishing
      sector for specific occupational risk factors, considering the latest and most
      advanced scientific knowledge. MATERIALS AND METHODS: The specific literature was
      analyzed to identify the occupational risk factors to which fishermen are
      exposed. Then, for each risk factor a protocol for the relative health checkups
      and their time schedule was defined. RESULTS AND DISCUSSION: The risk factors to
      which fishermen are exposed are essentially noise, vibrations, solar and
      ultraviolet radiation, climatic agents (heat, cold, wind, rain, damp), chemical
      agents, shifts, work rate, night work, physical strain, stress, manual handling
      of loads, upper limb repetitive tasks, incongruous postures. The health protocols
      stipulate the health screening investigations to be carried out in all workers of
      a homogeneous group, and in-depth diagnostic investigations to be carried out in
      symptomatic workers. Complementary health investigations must be focused on a
      functional exploration of the organs specifically exposed to the risk factor. For
      hearing impairments due to noise exposure, the medico-legal measures with which
      the occupational health physician must comply, in cases of occupational disease,
      are indicated.

PMID- 24303701
TI  - [Injuries in the maritime workers and fisheries].
AB  - This work is based on a Search conducted by IPSEMA and in course of publication.
      It was considered the accident trend of seafarers in the period 2004-2011, based
      on INAIL data. The category of vessels most affected by the accident phenomenon
      is passenger transport (about half of the cases), followed by cargo ships (20.2%)
      and fishing boats (16.0%). The average age of the injured is equal to 41.6 years.
      Further evidence relating to the qualification of seafarers injured (mostly
      "sailor", "hub" and "small") and nationality (94% of Italians), while the main
      mechanism of injury on board is the trauma that affects mostly the arts. In most
      cases, finally, it came to accidents that occurred during the navigation.

PMID- 24303702
TI  - [Management of chemical products and European standards: new classification
      criteria according to the 1272/2008 (CLP) regulation].
AB  - The European Union adopted regulations (EC) 1907/2006 REACH e (EC)1272/2008 CLP,
      to manage chemicals. REACH requires for evaluation and management of risks
      connected to the use of chemical substances, while o CLP provides for the
      classification, labelling and packagings of dangerous substances and mixtures by
      implementing in the EU the UN Globally Harmonised System of Classification and
      Labelling applying the building block approach, that is taking on board the
      hazard classes and categories which are close to the existing EU system in order
      to maintain the level of protection of human health and environment. This
      regulation provides also for the notification of the classification and labelling
      of substances to the Classification & Labelling Inventory established by the
      European Chemicals Agency (ECHA). Some european downstream regulations making
      reference to the classification criteria, as the health and safety laws at
      workplace, need to be adapted to these regulations.

PMID- 24303703
TI  - [Evolution of technology and occupational exposures in petrochemical industry and
      in petroleum refining].
AB  - The industry of oil refining and petrochemical play an important role in terms of
      number of employees in the Italian production. Often the terms "petroleum
      refining" and "petrochemical" are used interchangeably to define processes that
      occur in complex plants, which grow outdoors on large surfaces and a visual
      impact is not irrelevant. In reality, the two areas involve potential exposure to
      different chemical agents, related to raw materials processed and the specific
      products. The petrochemical uses as raw materials, the oil fractions, obtained by
      distillation in the refinery, or natural gas; petrochemical products are,
      usually, single compounds with a specific degree of purity, used as basic raw
      materials for the entire industry of organic chemistry, from the production of
      plastics to pharmaceuticals. The oil refining, that is the topic of this paper,
      processes mainly oil to obtain mixtures of hydrocarbon compounds, the products of
      which are specified on the basis of aptitude for use. For example gasolines, are
      obtained by mixing of fractions of the first distillation, reforming products,
      antiknock. The paper illustrates, necessarily broadly due to the complexity of
      the productive sectors, the technological and organizational changes that have
      led to a significant reduction of occupational exposure to chemical agents, the
      results of environmental monitoring carried out in some refineries both during
      routine conditions that during scheduled maintenance activities with plant
      shutdown and a store of petroleum products. The chemical agents measured are
      typical for presence, physico-chemical properties and toxicological
      characteristics of the manufacturing processes of petroleum products like
      benzene, toluene, xylenes, ethyl benzene, n-hexane, Volatile Hydrocarbons
      belonging to gasoline, kerosene, diesel fuel. Data related to both personal
      sampling and fixed positions.

PMID- 24303704
TI  - [Update on benzene: from industrial toxicant to environmental carcinogen].
AB  - Benzene, an industrial chemical myelotoxic at high doses in workers, is now an
      almost ubiquitous pollutant. It is also a no-threshold genotoxic carcinogen
      causing acute leukemia and other lymphoaematological tumours. Although its
      mechanism of action has not been fully clarified, benzene toxicity and
      carcinogenicity depend on metabolic activation. Polymorphism of activating and
      detoxifying enzymes (CYP, GST, NQO1) may be critical, therefore, in modulating
      individual susceptibility to benzene. Further uncertainty factors in assessing
      low level benzene exposure are the limited sensitivity and specificity of most
      exposure biomarkers, the frequent coexposure to other volatile organic chemicals
      (VOC), and the presence of non occupational sources of exposure, such as
      cigarette smoke and veicular traffic. The aim of this presentation is to
      introduce the main current critical issues in the risk assessment and the
      biological monitoring of occupational exposure to benzene at low doses.

PMID- 24303705
TI  - [Monitoring of the occupational and environmental exposure to low doses of
      benzene].
AB  - AIM: To verify which of the various biomarkers of internal dose of benzene can be
      considered reliable for biological monitoring of exposure to the low
      concentrations present nowadays in working and living environments. MATERIALS AND
      METHODS: The specific literature was analyzed to assess the reliability of the
      different biomarkers of internal dose. RESULTS AND CONCLUSIONS: T,t-muconic acid
      is a non specific biomarker for benzene, valid for exposure to concentrations up
      to one order of magnitude less than the threshold limit of 3250 microg/m3. S
      phenylmercapturic acid (SPMA) is a reliable marker even for exposure to
      concentrations up to two orders below the threshold value of 3250 microg/m3, and
      can be considered the biomarker of choice for biological monitoring of workers
      exposed to benzene. Urinary benzene does not seem to have any real advantages
      over SPMA for monitoring occupational exposure to benzene, but it does seem to be
      more reliable than SPMA to assess exposure to concentrations like those present
      in living environments. A smoking habit influences the urinary excretion of all
      the described biomarkers, and for the current low levels of occupational and
      environmental exposure to benzene, must be taken into account when interpreting
      the results of biological monitoring.

PMID- 24303706
TI  - [Methodological aspects in environmental and biological monitoring of exposure to
      low doses of benzene: problems and possible solutions].
AB  - This paper aims to examine some methods to measure human exposure to benzene,
      both in life and occupational environments, through environmental and biological
      monitoring, examining the critical issues and optimal conditions of use. The
      overall performance of environmental monitoring, from the analytical point of
      view, strongly depend on the choice of an appropriate method of sampling and
      analysis. Urinary SPMA and t, t-MA are the biomarkers listed by ACGIH to evaluate
      occupational exposure: most of the recent studies use HPLC with tandem mass
      spectrometry, but since t, t-MA is present in the urine in larger quantities it
      is also determinable with UV detectors. The urinary benzene is an index not
      officially included in the list of the ACGIH BEIs, but it is useful to assess
      exposure and benzene at low concentrations, that most frequently are found today
      in the occupational and life environments.

PMID- 24303707
TI  - [Biomarkers of effect and susceptibility to low doses of benzene].
AB  - Current occupational exposure levels to benzene are reduced by three orders of
      magnitudo (from ppm to ppb) as compared to the past. As benzene toxicity is
      related to its biotransformation and bioactivation pathways seem to be more
      active at lower exposure levels, observed effects could be higher than expected.
      Although the genetic polymorphisms of relevant and functional metabolic enzymes
      are implied in the modulation of either the risk of adverse effects
      [myeloperoxidase and NAD(P)H:quinone oxidoreductase] or of the biomarkers of
      internal dose (glutathione S-transferases M1-1, T1-1, A1-1), they are not
      appliable as biomarkers of susceptibility. Among biomarkers of early effect, only
      the longitudinal monitoring of blood cell count seems suitable to be applied in
      health surveillance protocols, whereas the use of biomarkers of genotoxic effect
      at current exposure levels is at the present not supported by literature data.

PMID- 24303708
TI  - [Epigenic modifications associated with low benzene exposure].
AB  - DNA methylation, mitochondrial DNA copy number and telomeres shortening are
      cellular modifications associated with an increasing number of tumors,
      cardiovascular and aging diseases. In our studies these modifications were
      evaluated in subjects occupationally exposed to low levels of benzene and in the
      general population. In peripheral blood lymphocytes a decrease of DNA methylation
      with the increase of personal benzene exposure was found, both in Alu and LINE-1
      repetitive elements, and in the global DNA. Telomere length shortening in
      subjects exposed to traffic exhausts and an increase in mitochondrial DNA copy
      number correlated to benzene exposure was also found. DNA methylation measured in
      specimen repeats collected at intervals of 8 years decreased more markedly in
      exposed subjects than in controls. Our studies highlighted the association of
      epigenetic modifications of DNA with low benzene exposure.

PMID- 24303709
TI  - [Considerations on the limit values for benzene].
AB  - Occupational exposure limits and guideline values for the general population
      proposed for benzene by several international bodies are discussed and compared
      with the Italian and EU occupational limit values, taking also into account the
      criteria used for their derivation. Benzene is an environmental pollutant, and
      the EU guideline value for ambient air is 5 microg/m3, based on carcinogenic
      risk. Presently, occupational exposures are greatly reduced, and in many
      instances close to those of the general population. Consequently, it does not
      seem to be appropriate to maintain the Italian and the EU occupational exposure
      limits of 1 ppm (3.2 mg/m3), which are inconsistent with the ALARA principle and
      not justified by technological constraints. It should be pointed out that, in any
      case, preventive interventions should be carried out, beyond the compliance with
      the established limit values, in order to ensure the lowest exposure and by
      carrying out biological monitoring as a tool to verify the appropriateness of
      risk management measures.

PMID- 24303710
TI  - [Health effects in petrochemical workers: cohort mortality studies in Italian
      plants].
AB  - The issue of carcinogenicty of petroleum chemicals has been extensively addressed
      in the scientific literature. The International Agency for Research on Cancer
      (IARC), in 1989, classified working in petroleum refineries in Group 2A (probable
      carcinogen) mainly due to increased risks for skin cancer and leukemia.
      Subsequent studies highlighted increased mortality from pleural mesothelioma. We
      present and discuss the findings of the mortality studies in four Italian
      petrochemical plants. The study population includes: 676 subjects employed in a
      plant near Rome, 1583 workers of a plant located in the Milan area, 903 workers
      employed in another northern petrochemical plant (Cremona area) and over 2000
      subjects who had worked in a similar plant in Sardinia (Cagliari area). Age
      gender-and calendar period adjusted Standardized Mortality Ratios (SMRs) and 95%
      Confidence Intervals (CI) were calculated using regional rates. Analyses by
      duration of employment and time since first employment were also performed.

PMID- 24303711
TI  - [Mortality and morbidity study of petrochemical workers in the context of the
      epidemiological characterization of a polluted site: the case study of Gela
      (Italy)].
AB  - BACKGROUND: The resident population of Gela (Sicily Region, Southern Italy) has
      shown excess mortality and morbidity risks probably related to the emissions from
      the local petrochemical plant. We present the methodology and main results of the
      occupational cohort studies of Gela petrochemical workers. METHODS: Standardized
      Mortality Ratios (SMRs) for specific causes were calculated using mortality rates
      of the Sicily Region as the reference. Internal analyses on mortality and
      morbidity (hospitalization) risks were also conducted by job and residence
      subcohorts. RESULTS: Observed deaths were less than expected for most causes of
      death. Internal analyses showed an increase in mortality from lung cancer, and an
      increase in the hospitalization for respiratory and genitourinary diseases among
      the blue collar subcohort and the Gela resident subcohort. CONCLUSION: The
      results of the internal analyses of mortality and morbidity suggest the need of
      indepth investigations into the occupational and environmental sources of
      exposure in the area.

PMID- 24303712
TI  - [Asbestos exposure in the petrochemical industry and interaction with other
      occupational risk factors: analysis of the last ten years INAIL data].
AB  - The present study analyzes the trend of occupational diseases, in particular
      those asbestos-related, in the petrochemical industry from 2002 to 2011, taking
      into account the number of diseases claimed to and compensated by the National
      Institute for Insurance of Workplace Accidents and Occupational Diseases (INAIL),
      assessing risk factors and possible interactions. To identify the research areas,
      we selected INAIL cost codes, related to the petrochemical industry. In the last
      five years, over the total claims submitted by industrial workers, 54% of claims
      for asbestosis, 76.7% of claims for neoplastic diseases, and 78.6% of claims for
      pleural plaques have been compensated. In the petrochemical industry, such
      percentages are respectively 59.2%, 81.6% and 82.7%. These data suggest possible
      interactions between asbestos and other risk factors, particularly significant in
      the petrochemical industry, although difficult to identify, as well as an initial
      underestimation of asbestos exposure in this industry.

PMID- 24303713
TI  - [The workplace injury trends in the petrochemical industry: from data analysis to
      risk management].
AB  - The most recent INAIL data show that, in 2009-2011, the accident frequency rate
      and the severity rate of workplace injuries in the chemical industry are lower
      than for the total non-agricultural workforce. The chemical industry, primarily
      because of the complex and hazardous work processes, requires an appropriate
      system for assessing and monitoring specific risks.The implementation of
      Responsible Care, a risk management system specific for the chemical industry, in
      1984, has represented a historical step in the process of critical awareness of
      risk management by the chemical companies. Responsible Care is a risk management
      system specifically designed on the risk profiles of this type of enterprise,
      which integrates safety, health and environment. A risk management system,
      suitable for the needs of a chemical company, should extend its coverage area,
      beyond the responsible management of products throughout the entire production
      cycle, to the issues of corporate responsibility.

PMID- 24303714
TI  - [Occupational diseases in the petrochemical sector: types and temporal trends].
AB  - In Italy, the archives of the National Institute for the Insurance of Workplace
      Accidents and Occupational Diseases (INAIL) are supported from several years by a
      second source of data on occupational diseases, the MALPROF system, based on data
      from the prevention units of the local health services (ASL). Integrating these
      two data flows allows connecting diseases and the occupations at the onset of the
      disease itself. The 2009-10 data from 12 Italian regions currently participating
      in the MALPROF system show that noise-induced hearing loss represents the
      relatively most frequent occupational disease (25.3%) in the petrochemical
      industry, followed by the musculoskeletal diseases (22.9%). Malignant tumors of
      the pleura and peritoneum follow with a proportional rate of 19%, six times
      higher than that recorded for the total industrial sectors (3.6%). Diseases of
      the respiratory system are clearly proportionally more frequent (16.5%) compared
      to data reported to the total industrial sectors (6%).

PMID- 24303715
TI  - [Agriculture in Italy nowadays: ancient risks and emerging diseases].
AB  - Since produce food using the environment, agricultural activities are fundamental
      for human and environmental health. They expose workers to all the known health
      and safety risks: pesticides and other chemicals, noise, vibrations, solar
      radiation, climate changes, organisational factors, biological, biomechanical and
      allergic risks. Also the risk of accidents is very relevant. Apart for these well
      known risks, new risks and diseases are emerging, such as biological risk from
      vectors, modulated by climate changes, or risks related to new production
      modalities, such as the cases of peripheral neuropathy observed in pig butchers.
      The risks can affect particularly vulnerable groups, such as seasonal, temporary
      workers and migrants. Currently, in Italy, an increase in reports of occupational
      diseases in the sector is being observed, in particular for musculoskeletal
      disorders. Such increase finds an explanation not in a worsening situation at the
      workplace but in an increasing attention for rural workers accompanied by an
      increased reporting of occupational diseases.

PMID- 24303716
TI  - [Vibration on agricultural tractors].
AB  - In the article, details related to the diffusion of agricultural tractors in
      Italy are given and considerations about the effects of vibration on operators,
      the sources of vibration and suggestions to reduce them are presented. The
      acceleration values observed in Italy amongst 244 tractors and levels of worker
      exposure are shown by means of histograms. The relevant data variability is
      discussed.

PMID- 24303717
TI  - [Chemical risk in farming].
AB  - The most important chemical risks in agriculture are plant protection products.
      Exposure evaluation in agriculture is not an easy task and cannot be carried out
      with the tools and methodologies of industrial exposures. However, toxicological
      studies on plant protection products, that are compulsory, provide a lot of
      useful information for actual risk assessment. Exposure evaluation can be carried
      out on the basis of exposure models and on semiquantitative measures based on the
      observation of the activity as it is carried our by the farmer. It is therefore
      possible to develop risk profiles that can guide exposure evaluation and health
      surveillance. Concentrated animal feeding operations are associated with several
      chemical risks including disinfectants, antibiotics, and gases such as ammonia
      and hydrogen sulfide, in addition to organic dusts and endotoxins.

PMID- 24303718
TI  - [Assessment and prevention of zoonoses: "one health approach"].
AB  - Zoonotic pathologies represent diseases that can be transmittable from animals to
      humans and vice versa. In most cases zoonotic agents are bacteria or viruses and
      represent a huge problem for health. Zoonosis could represent easily solvable
      diseases such as simple infections or even deathly such as prion infections. They
      could be directly transmittable as tuberculosis or brucellosis or indirectly
      transmittable through vectors as biological fluids or foods from animal
      production. The increasing production and the globalization of animal food
      production have caused the spread of zoonosis worldwide turning this topic into a
      global problem. It is necessary to enforce the actual scientific collaboration
      between all countries in order to counteract the spread of these pathologies.
      About this topic WHO, FAO and OIE took part to the world project "one health"
      highlighting as most important topics the research on Rabies virus, influenza
      virus and on antibiotic resistance. In particular antibiotic resistance
      represents one of the most important topics of the last decade due to the
      inappropriate use of antibiotics, from animal production to human health. This
      last topic represents a serious problem for health system worldwide. This paper
      is mainly based on zoonoses such as avian flu, BSE and brucellosis and will
      describe the strategies used to limit their expansion.

PMID- 24303719
TI  - [National plan for prevention in agriculture state of art and prosecution].
AB  - Agricultural work submits to high risks for safety and health. In 2009, in
      execution of "workplace health protection pact" (DPCM 17.12.2007), has been
      defined the National Plan for prevention in agriculture and forestry, whose first
      three-year program ended in 2012. Goals were: to Systematize and to standardize
      direction and control activity, defining the number of factories to control, in
      most italian regions, for high and ubiquitous risks applying homogeneous
      standards, spending special attention to risks of fatal and serious injury; to
      develop agricultural machinery trade control, for new and second-hand machinery,
      for normalizing the whole fleet; to contribute to monitoring of risk factors and
      injury dynamics, for a better definition of prevention policies; to increase the
      knowledge of public health agency officers; to identify and to promote technical
      solutions, helping to define, in proper way, good practices for complex problems;
      to promote coordination between economic develop policies and prevention policies
      for agriculture, breeding and forestry, paying attention also to financial helps.
      The plan, divided in regional plans, obtained most of defined goals and allowed
      to build a permanent interregional net of referents and expert officers. Next
      years perspective is to enhance in developing the faced themes and objectives.

PMID- 24303720
TI  - [Mechanisation sustainability of the agricultural chains: the case of viticulture
      in Lombardy].
AB  - Due to its strong impact on the ecosystem, the sustainability (mainly analyzed in
      its environmental, energy, production, economic, social and ethical requirements)
      is increasingly being felt in agriculture. With reference to the wine-growing
      sector, the most common solutions adopted to carry out the mechanized farming
      tasks have been examined, specifying in each case the critical issues and the
      most appropriate and innovative solutions.

PMID- 24303721
TI  - [Musculoskeletal disorders in farmers].
AB  - Musculoskeletal disorders are a relevant issue among farmers. From the literature
      it emerges a convincing evidence for an association of arthritis of the hip and
      work in the agricultural sector, while there is a less evidence when studying
      knee osteoarthritis and farming. For what concerns cervicobrachial pain, current
      available epidemiological data are not sufficient to define farmers at risk.
      Moreover, there is uncertainty about the role of hand-arm vibration as a strong
      risk factor among farmers. Overall, the high occurrence of musculoskeletal
      disorders among farmers highligths the need for more specific studies in order to
      assess the various tasks performed by agricultural workers from which to derive
      appropriate prevention interventions.

PMID- 24303722
TI  - [Human exposure to livestock pollutants].
AB  - The paper describes the sources and characteristics of the particulate matter
      (PM) generated in pig and poultry facilities. PM origins from the food, the
      peeling of the skin, loss of fur or feathers, from feces and litter, if present.
      The PM concentrations measured during the day change due to the management of the
      litter, the distribution of the food and the cleanliness of the shelters. There
      are several methods to protect the welfare of animals and stockmen, among which
      the ventilated ceilings are today the most innovative choice.

PMID- 24303723
TI  - [Prevention, diagnosis and management of the allergy risk in agriculture].
AB  - The agricultural sector represents a working environment in which nowadays
      allergies, mainly respiratory, are widely spread. In some cases, ubiquitous risk
      factors are involved, yet with a particular importance in the agricultural sector
      due to specific working occasions and housing conditions (see, for example,
      various pollens, mites and Hymenoptera). In other cases, specific risks arise
      mainly from the particular environmental conditions of the sheds allocated to the
      animals breeding or to the various cereals and fodder deposits. The result is the
      exposure to dust arising from the treated materials and the microbial and fungal
      agents present as pollutants. The underlying mechanisms of respiratory
      manifestations in the agricultural environment are still under study and have
      conflicting aspects. The agricultural sector still has, even in the developed
      countries, obvious lacks regarding both primary and secondary prevention. The
      main lack is present in the information and training activities which have proved
      to be efficient also in this occupational field. We will present some upgrading
      on the mentioned topics.

PMID- 24303724
TI  - [Accidents at work and occupational diseases trend in agriculture insurance
      management. The contribution of INAIL data's for the knowledge of a worrying
      phenomenon].
AB  - The author's describe accidents at work and occupational diseases outcome's
      measure in Agricolture insurance management acquired through statistical approach
      based on data processing provided by INAIL Bank data. Accident's incidence in
      Agricolture is compared to main insurance managements, using frequency index of
      accidents appearance selected on line of work and type of consequence. Concerning
      occupational diseases the authors describes the complaints and compensation with
      the comparison referring the analysis to statistical general data. The data
      define a worrying phenomenon.

PMID- 24303725
TI  - [Endemic zoonosis in Mediterranean area].
AB  - The Mediterranean is historically considered an area of high concentration of
      zoonoses. Mediterranean countries socio-economic features have favoured, over
      time, the onset of different types of zoonosis. Many of these may affect many
      occupational categories, first of all farmers, people working in abattoirs and
      processing products of animal origin. New farming activities and technologies
      have generated new occupational and zoonotic risks. These changes have influenced
      zoonosis epidemiology and have led to a gradual decrease in the number of
      diseases and to a reduction of some biological risks. However, brucellosis, Q
      fever, bovine tuberculosis cystic echinococcosis remain a strong example of
      zoonosis and a real risk, in the Mediterranean area especially. Therefore, an
      interdisciplinary collaboration between Veterinary Service, Public Health and
      Occupational medicine is necessary in order to plan territorial prevention.

PMID- 24303726
TI  - [Health care in agricultural work in the Sicilian Services of Prevention and
      Healthcare].
AB  - Agriculture is a work sector at high risk for the health of those who work there.
      The services of prevention and safety in the work area of the AA.SS.PP.
      (Provincial Health Agencies) of the Sicilian Region began a program of
      prevention, in the three year term 2010/2013, in this sector. A plan that has
      been laid out in the "Regional Plan for Prevention and Safety in Agriculture and
      Fowl Farming" outlined in DA (Administrative Decree number 1174/10. To be able to
      activate such a plan, the SPreSAL (Prevention and Health Service for the Work
      Area), have received extra resources that have permitted us to reach pre-planned
      objectives. The activity carried out brought to light serious defects, in respect
      to the maintenance of health and safety at work. These tend to derive mainly from
      the individual and family typologies of companies in the sector. For a more
      efficient activity of prevention we have shown the opportunity to underline and
      empower the preventative activity of a support type, rather than surveillance,
      and to reinforce the Services in such a way that, with their multi-disciplinary
      competences, they will be able to recover their capacity to carry out a direct
      control over the risk factors present in the work area.

PMID- 24303727
TI  - [Useful of animals as integrated rehabilitation in patients with psychological
      and physical discomfort].
AB  - In the context of social farming, understood as traditional agricultural
      production, there is a peculiarity appointed to generate innovative services of
      extreme importance from the health and social: the use of assisted therapy with
      animals for promoting the employment of disadvantaged people (handicapped). The
      proximity of the animal is to humans, and especially for young people, a great
      educational event, an important reference point for growth, a strong incentive to
      open up to the world, to communicate better, to gain a sense of responsibilities
      and to correct some defaillance behavioral and cognitive. This work attests to
      the validity of the animals as an aid in the treatment methodological
      neurorehabilitation of some diseases, emphasizing the importance of combining
      this new intervention strategy to conventional rehabilitation therapy.

PMID- 24303728
TI  - Cross cultural adaptation and validation of the Early Childhood Health Impact
      Scale (ECOHIS) in Peruvian preschoolers.
AB  - The aim of the present work was to perform semantic adjustment and evaluation of
      the psychometric properties of the Early Childhood Health Impact Scale (ECOHIS)
      in Spanish on a sample of the Peruvian population. The study was conducted on a
      sample of 128 children aged 3-5 years, who attended a public school (Hualmay
      District, Huaura Province, Lima, Peru) in 2011. The ECOHIS questionnaire,
      developed to measure the impact of oral conditions and/or experiences of dental
      treatment on oral health-related quality of life in children under 5 years old
      and their parents or other family members was adapted cross-culturally and
      subjected to psychometric tests: validity (in terms of construct and
      discriminant) and reliability (in terms of internal consistency and stability).
      The cultural adaptation addressed ECOHIS semantic equivalence (Bordoni et al.,
      2012) and showed that 80-100% of respondents understood the questions. Construct
      validity was r = .557 (p < .05) between the scores of the Spanish version of
      ECOHIS and dental caries experience (dmft). Statistically significant differences
      (p < .001) were found for ECOHIS values between groups with and without tooth
      decay. Internal consistency was assessed by Cronbach's alpha (.948) and stability
      by intra-class correlation (.992). The Peruvian version of ECOHIS demonstrated
      acceptable validity and reliability, enabling assessment of the impact of oral
      health problems in children under 5 years old.

PMID- 24303729
TI  - Oral health status and oral health-related quality of life in pregnant women from
      socially deprived populations.
AB  - The aim of the present work was to explore whether there is a relationship
      between oral health status and oral health-related quality of life in pregnant
      women from socially deprived populations in Buenos Aires City. Eighty pregnant
      women (age 18-39 x = 25.19 +/- 6.56) in their 1st/2nd trimester were sampled from
      the population of women visiting a health center located in the south of Buenos
      Aires City for their pregnancy check-ups. The impact of oral disease was assessed
      using the Spanish validated version (Lopez, 2006) of OHIP-49 (Slade and Spencer,
      1994), which includes 49 items grouped into 7 domains. Each question has five
      possible answers, to which values ranging from 1 to 5 were assigned. To assess
      oral health status, 4 calibrated researchers performed a clinical examination and
      recorded: Gingival Index (Loe and Silness, 1963); depth on probing, clinical
      attachment level, bleeding on probing and DMFT discriminating its components.
      Variables were analyzed in the population as a whole and in groups regarding
      previous dental attention (presence of fillings). Statistical analysis included:
      Chi Square test to establish association between variables and t-test to compare
      groups. 93.75% of the patients showed clinical signs of gingivitis, 2.5% showed
      clinical signs of periodontitis. Mean DMFT was 12.24 +/- 6.48 (D/DMFT = 6.46 +/-
      4.64; M/DMFT = 4.09 +/- 4.31; F/DMFT = 2.53 +/- 3.52); 73.3% of the patients had
      at least one missing tooth; 92.1% presented active caries lesions; 53.7% had at
      least one filling. Most frequent impacts were reported in the domains:
      psychological discomfort (59.9% = frequent concern about dental problems) and
      functional limitation (51.1% = frequent perception that "a tooth did not look
      good"). Oral health status and oral health-related quality of life showed no
      significant association. Domains involving functional limitation (p < 0.04) and
      physical disability (p < 0.01) showed higher levels of impact in the group of
      patients with previous dental care (presence of fillings). Oral health-related
      quality of life did not reflect health status; nevertheless, it may be an
      intervenient variable regarding demand for dental service.

PMID- 24303730
TI  - Oral health-related quality of life among Brazilian dental students.
AB  - This study was conducted to assess oral health-related quality of life (OHRQoL)
      among Brazilian dental students. A cross-sectional study was carried out
      involving 300 dental students at the Federal University of Parana, Brazil. To
      measure OHRQoL, the Oral Health Impact Profile (OHIP-14) was self-administered
      and a questionnaire was filled out addressing socio-demographic characteristics,
      health-related aspects and dental experience. Descriptive analysis was performed
      and both univariate and multivariate Poisson regression with robust variance were
      used to determine associations between OHRQoL and the covariables. The prevalence
      of reported impact on OHRQoL was 45 percent. The mean OHIP-14 score was 4.5. In
      the univariate analysis, the reason for the last visit to the dentist (p =
      0.004), reported discomfort in teeth/mouth (p < 0.001) and both self-rated
      general (p = 0.011) and oral (p < 0.001) health were significantly associated
      with OHRQoL. The year of academic education was not associated with OHRQoL (p =
      0.712). In the multivariate model, students who reported dissatisfaction with
      their teeth (PR = 1.32; IC 95%: 1.01-1.73), dental pain/sensitivity (PR = 2.36;
      IC 95%: 1.63-3.40), esthetic dental problems (PR = 1.45; IC 95%: 1.10-1.89),
      restorative needs (PR = 1.60; IC 95%: 1.01-2.55) and whose last visit to the
      dentist was for curative treatment (PR = 1.36; IC 95%: 1.05-1.76) had greater
      impact on OHRQoL. Aspects related to previous dental experience and self-reported
      oral health problems were associated with OHRQoL.

PMID- 24303731
TI  - Occurrence of aggressive periodontitis in patients at a dental school in southern
      Brazil.
AB  - Aggressive periodontitis is a rare, severe and rapidly progressing periodontal
      disease. Early diagnosis is of utmost importance for establishing treatment in
      order to stop periodontal destruction and prevent tooth loss. The aim of this
      study is to describe the occurrence of aggressive periodontitis in patients at a
      Dental School in Brazil by means of a cross-sectional study. First, records from
      patients aged 15-36 years were consecutively scrutinized. Patients should not
      have systemic diseases. The search went up to 383 valid records. By means of
      periapical radiographs, the distance between the cement-enamel junction and the
      bone crest was measured. Records in which there was severe bone loss or
      periodontal destruction incompatible with the age of the patient were selected.
      Patients with bone loss > or = 3mm were called to answer a questionnaire and
      undergo periodontal examination, in order to confirm or dismiss the diagnosis of
      aggressive periodontitis. From a total 383 records, 55.1% (211) were female and
      44.9% (172) were male. In 3.9% (15) of the records, presumed diagnosis was
      aggressive periodontitis, and 12 out of those 15 eligible patients (80%) came in
      for clinical examination and confirmation or dismissal of the diagnosis.
      Aggressive periodontitis was diagnosed in 7 patients, corresponding to 1.8% of
      the total. Of these, 4 (1% of the total) presented generalized aggressive
      periodontitis and 3 (0.8% of the total) presented localized aggressive
      periodontitis. In 5 patients (1.3%) chronic periodontitis was diagnosed. It may
      be concluded, within the limits of the study, that aggressive periodontitis at
      this Dental School is compatible with world prevalence values, suggesting the
      need for periodontal diagnosis as from adolescence, considering the possible
      damage caused by this disease.

PMID- 24303732
TI  - Theoretical evaluation of Nickel-Titanium Mtwo series rotary files.
AB  - Nickel-Titanium rotary files are a technological development that enables
      dentists to prepare irregularly shaped root canals without altering them.
      Unfortunately, these files may fracture without any prior visible warning signs.
      The aim of this study was to perform a theoretical evaluation of the mechanical
      behaviour of Mtwo Nickel-Titanium rotary files for endodontics, in order to
      determine which of the files in the basic series are most likely to fracture.
      Mathematical models of the Mtwo basic file series were analyzed using the finite
      elements method. Bending and torsion loads were applied to the files both under
      normal conditions and under extreme conditions, to determine which of them had
      the highest Von Mises stresses. When the approximation was similar to normal use
      none of the file models reached the maximum limit of failure by fracture. When
      used inadequately, file models 10/0.04 and 25/0.06 had the highest Von Mises
      stresses for bending and torsion, respectively. Thus, it is recommended that Mtwo
      files 10/0.04 and 25/0.06 should be used once only, to prevent fractures.

PMID- 24303733
TI  - Alveolar wound healing in rats fed on high sucrose diet.
AB  - The potential for bone repair is influenced by various biochemical,
      biomechanical, hormonal, and pathological mechanisms and factors such as diet and
      its components, all of which govern the behavior and function of the cells
      responsible for forming new bone. Several authors suggest that a high sucrose
      diet could change the calcium balance and bone composition in animals, altering
      hard tissue mineralization. The mechanism by which it occurs is unclear. Alveolar
      healing following tooth extraction has certain characteristics making this type
      of wound unique, in both animals and humans. The general aim of this study was to
      evaluate and quantify the biological response during alveolar healing following
      tooth extraction in rats fed on high sucrose diets, by means of osteocyte lacunae
      histomorphometry, counting empty lacunae and measuring areas of bone quiescence,
      formation and resorption. Forty-two Wistar rats of both sexes were divided into
      two groups: an experimental group fed on modified Stephan Harris diet (43%
      sucrose) and a control group fed on standard balanced diet. The animals were
      anesthetized and their left and right lower molars extracted. They were killed at
      0 hours, 14, 28, 60 and 120 days. Samples were fixed, decalcified in EDTA and
      embedded in paraffin to prepare sections for optical microscopy which were
      stained with hematoxylin/eosin. Histomorphometric analysis showed significant
      differences in the size of osteocyte lacunae between groups at 28 and 60 days,
      with the experimental group having larger lacunae. There were more empty lacunae
      in the experimental group at 14 days, and no significant difference in the areas
      of bone activity. A high sucrose diet could modify the morphology and quality of
      bone tissue formed in the alveolus following tooth extraction.

PMID- 24303734
TI  - Antimicrobial activity of fractions and subfractions of Elaeagia utilis against
      microorganisms of importance in dental caries.
AB  - Dental caries is a multifactorial infectious disease that leads to the
      destruction of dental hard tissue. The main goal of research into medicinal
      plants is to seek compounds with antimicrobial activity for subsequent use in
      prevention strategies and control of infectious diseases. The aim of this study
      was to evaluate the antimicrobial activity of fractions and subfractions obtained
      from Elaeagia utilis against Streptococcus mutans, Streptococcus sobrinus and
      Lactobacillus acidophilus. The plant material was collected in the town of Alban
      (Cundinamarca, Colombia), which is located at an altitude of 2245 meters above
      sea level. Two extracts were obtained by cold maceration of E. utilis leaves in
      (a) petroleum ether extract and (b) ethanol extract. Fractions were obtained from
      the petroleum ether extract by column vacuum chromatography, and from the ethanol
      extract by continuous liquid/liquid partitioning. The antimicrobial activity of
      fractions and subfractions was evaluated by the well diffusion method. At a
      concentration of 10 mg/well, several fractions from both extracts showed
      antimicrobial activity against S. mutans, S. sobrinus and L. acidophilus. Among
      the ethanol extract fractions, the dichloromethane fraction had notably greater
      antimicrobial activity. It was sub-partitioned, yielding three subfractions with
      inhibitory activity, of which the most active was MeOH: H2O (Bp) with minimum
      inhibitory concentration 0.1 mg/well on the 3 study bacteria. Terpenes,
      sesquiterpenlactones and simple phenolic compounds were identified in it. In
      conclusion, this study shows the antimicrobial potential of fractions and
      subfractions obtained from extracts of E. utilis leaves against bacteria that are
      important in dental caries.

PMID- 24303735
TI  - Influence of irrigation and obturation techniques on artificial lateral root
      canal filling capacity.
AB  - The aim of this study was to evaluate the influence of two different irrigation
      protocols on artificial lateral root canal filling capacity using different
      obturation techniques. Sixty single-root human teeth were used. Two artificial
      lateral canals were created in the apical third. Root canals were instrumented up
      to a 45 K-file to the working length. Before each file, root canals were
      irrigated either with 2 mL of 2.5% NaOCl or 2% chlorhexidine gel with further
      irrigation with saline solution and 3 mL of 17% EDTA. Specimens were randomly
      divided into three groups according to the obturation technique: (1) lateral
      compaction technique; (2) Tagger hybrid technique; and (3) thermoplasticized
      technique using BeeFill 2 in 1. All groups used AH Plus as the root canal sealer.
      The specimens were decalcified and cleared in methyl salicylate. The total length
      of lateral canals was observed under X30 magnification with a stereomicroscope
      and measured on the buccal and lingual root surfaces using Leica IM50 software.
      The data were submitted to ANOVA and Tukey test (p < 0.05). Among the obturation
      techniques, BeeFill 2 in 1 showed deeper penetration into all lateral canals than
      the lateral compaction or Tagger hybrid techniques (p < 0.05). The lateral
      compaction group showed the worst results (p < 0.05). Irrigants did not affect
      the outcome; there was no difference between NaOCl and chlorhexidine when the
      same obturation technique was used (p > 0.05). Regardless of the irrigant used
      during endodontic procedures, the thermoplasticized techniques showed higher
      penetration behavior for filling artificial lateral canals than the lateral
      compaction technique.

PMID- 24303736
TI  - Oxidative stress assessed in saliva from patients with acute myocardial
      infarction. A preliminary study.
AB  - There is evidence that acute myocardial infarction (AMI) is associated with
      increasing production of reactive oxygen species and tissue injury. The aim of
      this study was to assess the presence of oxidative stress indices in saliva 24
      and 48h after AMI. MATERIALS AND METHODS: We designed a prospective study
      comparing salivary levels of biomarkers of oxidative stress in patients with AMI
      with elevation of the ST segment in electrocardiogram versus clinically healthy
      subjects. Oxidative stress indices including the rate of oxidation of 2'7'
      dichlorohydrofluorescein diacetate (DCFH-DA) and the activity of the antioxidant
      enzyme catalase (CAT) were evaluated in saliva from patients with AMI at 24 and
      48 hours. At each sampling time, blood was drawn for serum markers of myocardial
      infarction. RESULTS: This study included ten patients with acute ST-segment
      elevation myocardial infarction and ten clinically healthy controls. Mean age was
      67.8 +/- 11.1 vs. 48.7 +/- 4.1 years (p < 0.001) and gender was 60% male vs. 50%
      (p > 0.05) for AMI vs. controls, respectively. Our results demonstrated an
      increase in the rate of oxidation of DCFH-DA in the myocardial infarction group
      as compared with controls (p = 0.004), which remained unchanged at 48h. There was
      no difference in salivary catalase activity between controls and AML subjects at
      24h or at 48h post-diagnosis (p = 0.157). The relationship between CAT48 and DCFH
      DA48 was fairly significant (r = 0.39; p = 0.053). CONCLUSION: This preliminary
      study showed that biomarkers of oxidative stress are detectable in saliva of
      patients with acute myocardial infarction. CLINICAL RELEVANCE: Future studies
      using a larger population are needed to confirm these observations and to explore
      the possibility of using the saliva to monitor evolving diagnosis and prognosis
      in acute coronary syndrome.

PMID- 24303737
TI  - Radiopacity and flow of different endodontic sealers.
AB  - The present study evaluated the radiopacity and flow of different endodontic
      sealers: AH Plus, Endo CPM, MTA Fillapex, Sealapex, Epiphany, and Epiphany SE.
      For the radiopacity test, six specimens measuring 10 mm in diameter and 1 mm in
      thickness were fabricated from each material. They were radiographed on an
      occlusal film alongside an aluminum step wedge. Radiographs were digitized to
      determine the radiopacity equivalence in millimeters of aluminum. To evaluate the
      flow, a 120 g load was placed on top of a glass slab containing 0.05 +/- 0.005
      mll of sealer. The diameters of each material were measured (mm) with a caliper
      and samples were photographed. Digitized images were analyzed using the UTHSCSA
      Image Tool for Windows software, to determine the sealer area (mm2). Data were
      submitted to ANOVA and Tukey's test at 5% significance. AH Plus and Epiphany SE
      presented the greatest radiopacity (12.5 mm Al and 12.0 mm Al, respectively) (p >
      0.05), followed by Epiphany (9.6 mm Al) and Fillapex (8.9 mm Al). Endo CPM (5.46
      mm Al) and Sealapex (5.51 mm Al) presented lower radiopacity. MTA Fillapex
      presented significantly higher values of flow than other sealers (33.11 mm and
      844.9 mm2). AH Plus, Epiphany, and Epiphany SE had similar values. Endo CPM
      (21.05 mm and 342.8 mm2) and Sealapex (19.98 mm and 352.5 mm2) presented the
      lowest flow values (p > 0.05). All sealers presented radiopacity and flow values
      according to ISO and ANSI/ADA recommendations.

PMID- 24303738
TI  - [Fiber reinforced composite posts: literature review].
AB  - FRC (Fiber-reinforced composite) posts have been used since the beginning of the
      90s with the introduction of carbon fiber posts. Fiber posts are widely used to
      restore endodontically treated teeth that have insufficient coronal tooth
      structure. Many in vitro and in vivo studies have shown the advantage of using
      FRC over prefabricated and cast metal post especially indicated in narrow root
      canals which are prone to vertically root fracture. The most frequent failure of
      FRC is debonding of a post at the resin cement/dentin interface. Bonding to
      dentin may be achieved by using etch-and-rinse and self-etch adhesives. The bond
      strength formed by self-adhesive cements is noticeably lower in comparison to the
      bond strength formed with resin cements applied in combination with etch-and
      rinse adhesives. In an attempt to maximize resin bonding to fiber posts, several
      surface treatments have been suggested. Sandblasting with alumina particles
      results in an increased surface roughness and surface area without affecting the
      integrity of the post as long as it is applied by 50 microm alumina particles at
      2.5 bars for maximally 5 seconds at a distance of 30 mm. The efficiency of post
      salinization is controversial and its contribution to the retention is of minor
      importance. Hydrofluoric acid has recently been proposed for etching glass fiber
      posts but this technique produced substantial damage to the glass fibers and
      affected the integrity of the post. Delayed cementation of fiber post (at least
      24h post endodontic treatment) resulted in higher retentive strengths in
      comparison to immediate cementation and the best results were obtained when the
      luting agent was brought into the post space with lentulo spirals or specific
      syringes. The resin cement film thickness also influences the pullout strengths
      of fiber-reinforced posts .The highest bond strength values were obtained when
      the cement layer oversized the post spaces but not larger than 0.3 mm. The use of
      core build-up materials as post luting cements is not recommended. The use of FRC
      post, combined with proper adhesive cementation technique can give an excellent
      solution when restoring endodontically treated teeth that are prone to fracture.

PMID- 24303739
TI  - [Orthodontic silicone positioner for the treatment of oral symptoms in
      Amyotrophic Lateral Sclerosis (ALS) patients].
AB  - ALS is considered a neurodegenerative disorder caused by progressive death of
      specific neuronal populations within the gray matter of the central nervous
      system. The cause of cell death is unknown and patients with ALS will live 3 to 5
      years from disease onset. A common cause of death is neuromuscular respiratory
      failure or cardiac arrhythmias due to insufficient oxygen. The patients develop
      multiple symptoms and the focus of management is to maintain their quality of
      life. Orofacial manifestations in ALS are secondary to motor deficits, resulting
      in dysphagia, muscle spasticity, rigidity and tremor of the orofacial
      musculature, which can induce soft tissue trauma and sialorrhea. In this report
      the management of ALS oral symptoms, by means of an elastic silicone full
      coverage occlusal splint, often used as an orthodontic positioner, is discussed,
      as well as its advantages and alternatives. The positioner was easily tolerated
      by the patients who reported improvement in soft tissue trauma lesions due to
      accidental self biting, and improved control of the drooling due to excessive
      saliva and difficulty in swallowing.

PMID- 24303740
TI  - [Revascularization? Only as the last resort!].
AB  - Revascularization has been suggested for treatment of necrotic immature permanent
      teeth. The desirable outcome of the treatment is continuous growth of the root,
      maturation of the dentin walls underneath the cervical seal and apical closure.
      Despite of increasing numbers of case reports, a uniform treatment protocol has
      not been set. This procedure has many shortcomings of which tooth discoloration
      is the most prevalent and easy to observe. The severe discoloration is attributed
      to the use of Mincocycline in the antibiotic dressing, or to the use of MTA for
      the seal. The maturation of the root is not predictable and does not always
      occur. The outcome should be evaluated radiographically and clinically.
      Sensibility testing may not be possible due to the large MTA plug in the root
      canal. It is recommended only when alternative procedures such as apexificaiton,
      pulpotomy or pulp capping are impossible. The patient and his parents should be
      aware of the potential discoloration and must be committed to routine follow ups.
      Currently, this procedure should be limited to incisor or premolar teeth in which
      the crown is longer than the root, or the canal's width is larger than that of
      the dentinal wall.

PMID- 24303741
TI  - [Teeth--too early to eulogize!].
AB  - With the growing use of dental implants and the high success and survival rates,
      less effort is being made for treating and preserving teeth. Teeth, on some
      cases, are being extracted too early and become more affected by service
      interventions than by oral diseases. Though dental implants, bone grafts and
      other augmentation techniques are rather successful, the real long term results
      of such cases are not always highly predictable. Teeth have been proven over the
      years to survive for a very long time with an appropriate treatment and
      maintenance. Before declaring a tooth to be hopeless and scheduled for
      extraction, careful thought should be taken if this tooth is really hopeless and
      cannot be preserved. Risk factors for dental implant survival and success such as
      cigarette smoking, periodontal disease, and diabetes mellitus should also be
      accounted for. It should be kept in mind also, that nowadays, we are much better
      in treating periodontitis than we are in treating periimplantitis.

PMID- 24303742
TI  - [Comprehensive dental treatment under general anaesthesia: implementation among
      patients with mouth opening limitation].
AB  - Patients unable to tolerate routine dental treatment in an ordinary dental
      setting may undergo a wide range of dental procedures under general anaesthesia.
      This report describes a practical protocol for providing comprehensive dental
      treatment under general anaesthesia. The importance and uniqueness of planning,
      treating and adopting safety measures is illustrated through the presentation of
      clinical cases of patients with mouth opening limitation. Complete treatment can
      thus be achieved in a single visit, thereby eliminating repetition of coping with
      anxiety associated with repeated treatment sessions.

PMID- 24303744
TI  - [Listen to your body].

PMID- 24303743
TI  - [Impressions for implant supported prostheses].
AB  - A crucial aspect for successful outcome of implant supported restoration is it's
      accurate fit. The implant and the prosthetic component have precise machine fit,
      thus small discrepancies can lead to stress applied to the implants when
      connecting the restoration. The accuracy of the master cast is of great
      significance and depends on both clinical and laboratory factors. The purpose of
      this article is to discuss the various materials and methods available for
      impressions and the effect of implants' location, number and angulations on the
      accuracy of the impressions.

PMID- 24303745
TI  - Aging faces and aging perceivers: young and older adults are less sensitive to
      deviations from normality in older than in young adult faces.
AB  - Past studies examining the other-age effect, the phenomenon in which own-age
      faces are recognized more accurately than other-age faces, are limited in number
      and report inconsistent results. Here we examine whether the perceptual system is
      preferentially tuned to differences among young adult faces. In experiment 1
      young (18-25 years) and older adult (63-87 years) participants were shown young
      and older face pairs in which one member of each pair was undistorted and the
      other had compressed or expanded features. Participants indicated which member of
      each pair was more normal and which was more expanded. Both age groups were more
      accurate when tested with young compared with older faces-but only when judging
      normality. In experiment 2 we tested a separate group of young adults on the same
      two tasks but with upright and inverted face pairs to examine the differential
      pattern of results between the normality and discrimination tasks. Inversion
      impaired performance on the normality task but not the discrimination task and
      eliminated the young adult advantage in the normality task. Collectively, these
      results suggest that the face processing system is optimized for young adult
      faces and that abundant experience with older faces later in life does not
      reverse this perceptual tuning.

PMID- 24303746
TI  - Receivers in American football use a constant optical projection plane angle to
      pursue and catch thrown footballs.
AB  - In the present work we test how well two interceptive strategies, which have been
      proposed for catching balls hit high in the air in baseball and cricket, account
      for receivers in American football catching footballs. This is an important test
      of the domain generality of these strategies as this is the first study examining
      a situation where the pursuer's locomotor axis is directed away from the origin
      of the ball, and because the flight characteristics of an American football are
      far different from targets studied in prior work. The first strategy is to elicit
      changes in the ball's lateral optical position that match changes in the vertical
      optical position so that the optical projection plane angle, psi, remains
      constant, thus resulting in a linear optical trajectory (LOT). The second is
      keeping vertical optical ball velocity decreasing while maintaining constant
      lateral optical velocity (generalized optical acceleration cancellation, or
      GOAC). We found that the optical projection plane angle was maintained as
      constant significantly more often than maintaining vertical and lateral optical
      velocities as GOAC predicted. The present experiment extends previous research by
      showing that the constancy of psi resulting in an LOT is used by humans pursuing
      American footballs and demonstrates the domain generality of the LOT heuristic.

PMID- 24303747
TI  - Infants see illusory motion in static figures.
AB  - We investigated illusory motion perception in 6-to-8-month-old infants using a
      static figure which produces strong illusory motion. In experiment 1 we prepared
      a control figure, which was physically similar to the illusory motion figure but
      which did not produce illusory motion. We presented the illusory figure and the
      control figure side-by-side, and measured infants' looking time at the target
      illusory figure. Results showed that the infants' looking time at the illusory
      figure was significantly longer than that for the control. In experiment 2 we
      made another set of stimuli consisting of the same local pattern used in
      experiment 1, but which did not produce illusory motion. The results showed that
      no preferences were observed in experiment 2. These results suggest that 6-to-8
      month-old infants perceive illusory motion in static figures.

PMID- 24303748
TI  - Facial coding is disrupted at equiluminance.
AB  - Human face recognition is disrupted by the reversal of luminance contrast
      polarity (ie photo negatives--see Galper 1970 Psychonomic Science 19 207-208;
      Johnston et al 1992 Perception 21 365-375), while recognition of other objects is
      less impacted (Nederhouser et al 2007 Vision Research 47 2134-2142; Subramaniam
      and Biederman 1997 Investigative Ophthalmology & Visual Science 38 998). This
      suggests that correct patterns of luminance contrast are important for facial
      coding. Here we investigate this further by minimising luminance contrast. We
      contrast peoples' ability to categorise cars and faces when images vary in
      luminance and when images are altered to predominantly contain differences in
      colour (equiluminance). Eliminating luminance contrast had a greater adverse
      impact on facial classifications relative to car categorisations. This was true
      even though precautions were taken to equate visibility, and despite equal levels
      of performance when images contained luminance contrast. These results were not
      due to images containing markedly different spectra, as the effect persisted for
      facial images altered to match car images in this regard, and performance in both
      tasks dropped off proportionally with increasing levels of image blur. Finally,
      consistent with previous observations, we show that facial coding is not only
      adversely impacted at equiluminance but becomes even worse when the polarity of
      luminance contrast is reversed. Our data show that the correct pattern of
      luminance contrast is very important for facial coding. We suggest that this is
      related to the role of luminance contrast in signalling 3-D shape from shading.

PMID- 24303749
TI  - On the generality of the topological theory of visual shape perception.
AB  - This study used a series of six closely related experiments to examine whether
      individuals use topological structures to discriminate figures. Strict control
      was exerted over the selection of stimuli, which were a specific type of randomly
      generated lined figures that can be classified using isomorphic sets defined by
      graph theory. Any two figures within an isomorphic set possessed the same
      topological structure. The experiments described here used a same/different
      discrimination task with simultaneously presented pairs of figures: (a) identical
      pairs (Id pairs), in which each pair of figures had the same topological and
      superficial properties; (b) nonidentical and isomorphic pairs (Iso pairs), in
      which each pair had the same topological but different superficial properties;
      and (c) nonidentical and nonisomorphic pairs (Noniso pairs), in which each pair
      had different topological properties. Within these experiments I varied the
      conditions related to the intersecting line segments, presentation of points
      defining each figure, figure complexity, stimulus aspect ratios, and the parity
      of the total line-segment lengths between the figures in each pair. These
      variations showed that the latencies for making accurate discriminations were
      shorter for Noniso pairs than for Iso pairs, suggesting that individuals are
      sensitive to topology when distinguishing figures.

PMID- 24303750
TI  - Interference effect of body shadow in action control.
AB  - Observing actions performed by other persons can subsequently influence our own
      motor behaviours. However, it is unknown whether the shadows cast by such actions
      can also have an impact on the observers' actions. Here we show that the mere
      observation of a cast shadow can influence imitative behaviours. Specifically,
      participants were shown a hand picture and its associated cast shadow in a
      neutral position. In a 'compatible trial' the hand and the shadow that followed
      were turned in the same open or closed direction, whereas in an 'incompatible
      trial' the hand and the shadow were turned in different directions. We contrasted
      two experimental conditions: (i) 'hand-shadow' in which participants observed a
      hand and its cast shadow (the hand covered the shadow); (ii) 'hand-hand' in which
      participants observed a hand and another black hand (the shadow covered the
      hand). The participants' task was to imitate (ie by closing or opening their own
      hands) the hand or the cast shadow of an action. For both conditions results
      revealed interference (ie longer response latencies) for incompatible trials.
      This suggests for the first time that the mere observation of a cast shadow of a
      hand can influence imitative behaviours. However, time courses of the response
      latencies revealed that imitative effect in the hand-shadow condition was
      different than the imitative effect in the hand-hand condition. Therefore, we
      suggest considering the cast shadow of an action as an important feature during
      motor control for humans.

PMID- 24303751
TI  - Change blindness in a dynamic scene due to endogenous override of exogenous
      attentional cues.
AB  - Change blindness is a failure to detect changes if the change occurs during a
      mask or distraction. Without distraction, it is assumed that the visual
      transients associated with the change will automatically capture attention
      (exogenous control), leading to detection. However, visual transients are a
      defining feature of naturalistic dynamic scenes. Are artificial distractions
      needed to hide changes to a dynamic scene? Do the temporal demands of the scene
      instead lead to greater endogenous control that may result in viewers missing a
      change in plain sight? In the present study we pitted endogenous and exogenous
      factors against each other during a card trick. Complete change blindness was
      demonstrated even when a salient highlight was inserted coincident with the
      change. These results indicate strong endogenous control of attention during
      dynamic scene viewing and its ability to override exogenous influences even when
      it is to the detriment of accurate scene representation.

PMID- 24303752
TI  - DaVinci's Mona Lisa entering the next dimension.
AB  - For several of Leonardo da Vinci's paintings, such as The Virgin and Child with
      St Anne or the Mona Lisa, there exist copies produced by his own studio. In case
      of the Mona Lisa, a quite exceptional, rediscovered studio copy was presented to
      the public in 2012 by the Prado Museum in Madrid. Not only does it mirror its
      famous counterpart superficially; it also features the very same corrections to
      the lower layers, which indicates that da Vinci and the 'copyist' must have
      elaborated their panels simultaneously. On the basis of subjective (thirty-two
      participants estimated painter-model constellations) as well as objective data
      (analysis of trajectories between landmarks of both paintings), we revealed that
      both versions differ slightly in perspective. We reconstructed the original
      studio setting and found evidence that the disparity between both paintings
      mimics human binocular disparity. This points to the possibility that the two
      Giocondas together might represent the first stereoscopic image in world history.

PMID- 24303753
TI  - Approaching Stan Laurel's illusion: the self-induced rubber hand phenomenon.
AB  - The classical rubber hand illusion is induced by an experimenter (eg stimulation
      with a brush) and usually realized with some sort of visual occlusion. Here, we
      demonstrate a new phenomenon: the self-induced rubber hand illusion. It is
      possible to elicit the feeling of a third hand without any help from an
      experimenter and under conditions of no occlusion. The findings are discussed
      within the context of neural plasticity.

PMID- 24303754
TI  - [Expression of VCAM-1 and caspase-3 in myocardium of persons who died from viral
      myocarditis].
AB  - OBJECTIVE: To observe the expression and distribution of vascular cell adhesion
      molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral
      myocarditis and to explore its pathogenesis and death mechanism. METHODS: Twenty
      cases died from viral myocarditis were selected as the experimental group. Ten
      cases died from traumatic shock and massive hemorrhage shock after traffic
      accidents were selected as the control group. The sections of myocardium were
      stained by immunohistochemistry for VCAM-1 and caspase-3, and observed under
      microscope. The positive expressions of VCAM-1 and caspase-3 of the two groups
      were compared with each other by image analysis and statistical analysis.
      RESULTS: (1) The vascular endothelial cells expressed VCAM-1 with dark nigger
      brown colors in the experimental group, and weak expression was observed in the
      control group. The average optical density in the experimental group was higher
      than that in the control group (P < 0.05). (2) The caspase-3 positive cells were
      mostly inflammatory cells around the myocardial vessels with brown-red granules
      in the experimental group. The positive cell number in the experimental group was
      higher than that in the control group (P < 0.05). CONCLUSION: VCAM-1 may play an
      important role in the inflammatory cells exudation caused by viral myocarditis,
      and may provide the reference for diagnosis of viral myocarditis in forensic
      pathology. However, the myocardial apoptosis mediated by caspase-3 doesn't affect
      the lethal mechanism in the late stage of viral myocarditis.

PMID- 24303755
TI  - [Myocardial expression of Spry1 and MAPK proteins of viral myocarditis].
AB  - OBJECTIVE: To discuss the myocardial expression of Spry1 and MAPK proteins of
      viral myocarditis (VMC), to reveal its mechanism of sudden death, and to provide
      guides for forensic identification of sudden cardiac death. METHODS: Thirty
      Balb/c male mice were randomly divided into VMC group and control group,
      inoculated intraperitoneally with Coxsackievirus B3 and Eagel's solution,
      respectively. After the mice were sacrificed, the cardiac tissues of the mice
      were taken to proceed regular pathological examination. The changes of Spry1
      protein, Spry1 mRNA and MAPK protein were detected by immunohistochemistry,
      Western blotting and real-time PCR. RESULTS: Under light microscope, the
      pathologic changes included myocardial interstitial edema, inflammatory cells
      infiltration, myocardial necrosis, and focal and patchy necrosis of myocardial
      fiber in VMC group. The expression of Spry1 protein in VMC group was lower than
      that in control group (P < 0.05). There was slightly decreased expression of
      Spry1 of the mRNA level in VMC group (P > 0.05). But the MAPK protein expression
      in VMC group was higher than that in control group (P < 0.05). CONCLUSION: The
      pathway of MAPK/ERK involving Spry1 protein accelerates the expression of
      collagen, which may contribute to arrhythmia, heart failure and even sudden
      cardiac death.

PMID- 24303756
TI  - [The staging method of sternal end of clavicle epiphyseal growth by thin layer CT
      scan and imaging reconstruction].
AB  - OBJECTIVE: To establish a CT staging method of sternal end of clavicle epiphyseal
      growth for teenagers by thin layer CT scan, multiplanar reconstruction (MPR) and
      volume reconstruction (VR) technologies. METHODS: The CT imaging characteristics,
      which collected from 460 teenagers (aged from 15 to 25) in East and South China,
      were studied through both sternal ends of clavicles' imagings by thin layer
      coronal CT scan and axial CT scan, MPR and VR technologies. The parameters of
      sternal end of clavicle including the longest diameter of epiphysis, the longest
      diameter of metaphysis, their length ratio, area of epiphysis, area of
      metaphysis, and their area ratio were measured and calculated in order to
      establish new classification. RESULTS: Based on the staging method of Schmeling,
      integrating the CT imaging reconstruction information of sternal end of clavicle,
      the new classification of sternal end of clavicle epiphyseal growth were divided
      into 1 to 5 stages, and stage 2 and stage 3, respectively, contained a, b and c
      sub-classification. CONCLUSION: This new classification has merits of large
      sample size, wide age range and easy operability. By using CT imaging
      reconstruction techniques and analyzing the data which closely related to sternal
      end of clavicle epiphyseal growth of teenagers, the feasibility of the staging
      method could be increased.

PMID- 24303757
TI  - [The evaluation of SCI by TMS-MEP and its forensic significance].
AB  - OBJECTIVE: To find an objective and accurate examination for evaluation of spinal
      cord injury (SCI) in forensic clinical medicine. METHODS: The onset latency of
      cortex, peak latency of N1, central motor conduction time (CMCT) and wave width
      of the abductor pollicis brevis and the anterior tibialis were calculated by
      transcranial magnetic stimulation-motor evoked potential (TMS-MEP). The data of
      68 patients suffered from SCI including 23 cervical levels and 45 thoracolumbar
      levels were collected and compared with that of 30 normal controls. RESULTS: In
      experimental group, when the muscle strength of the abductor pollicis brevis or
      the anterior tibialis decreased or disappeared, the onset latency of cortex, the
      peak latency of N1, and CMCT prolonged and the wave width broadened. And these
      indexes of grade 2 and 3 muscle strength in experimental group were higher than
      that in the control group (P < 0.05). CONCLUSION: The TMS-MEP can determine
      directly and objectively the motor functional status of pyramidal tract of spinal
      cord in order to provide more accurate and objective evidences in forensic
      medicine.

PMID- 24303758
TI  - [Morphological characteristics of hyoid bone and its gender difference].
AB  - OBJECTIVE: To understand and analyze the morphological characteristics of hyoid
      bone and its gender difference in order to find out its forensic significance.
      METHODS: The hyoid bones of 68 adult corpses were dissected from redundant soft
      tissues after heating. The connection status of body of hyoid, greater cornu and
      lesser cornu, the morphological characteristics of hyoid bone and the degree of
      ossification were observed by visual inspection. The height of hyoid bone and the
      arched height of hyoid bone were measured and compared the differences between
      male and female in order to deduce the analytic equation for gender estimation by
      hyoid bone. RESULTS: Five connection conditions of hyoid bone were identified by
      the morphological characteristics, including complete ossification in both sides,
      no ossification in both sides, partial ossification in both sides, complete
      ossification in one side (partial ossification in the other side), and complete
      ossification in one side (no ossification in the other side). The values of the
      arched height of hyoid bone (x1) and the height of hyoid bone (x2) in male were
      both higher than that in female (P < 0.01). The analytic equation for gender
      estimation (y) was y = 0.438 x1 + 1.042x2-12.979. The discriminant value was 
      0.272 5 and the resolution was 88.2%. CONCLUSION: According to the gender
      characteristics of hyoid bone, the data of hyoid bone can provide helps for
      forensic practices.

PMID- 24303759
TI  - [Calculation of likelihood ratio for X-STR typing in kinship testing].
AB  - OBJECTIVE: To deduce the calculation formulae of likelihood ratio for kinship
      testing with X-short tandem repeat (X-STR) typing. METHODS: With the identity by
      decent coefficient of different relationships, the joint genotypic probability of
      two individuals with specific genotypes was calculated as X value, and then the
      joint genotypic probability of two unrelated individuals was calculated as Y
      value; therefore, the likelihood ratio value (X/Y) was obtained. RESULTS: The
      calculation formulae of the likelihood ratio for different genotype combinations
      of the female-female, female-male and male-male genetic relationships were
      derived and verified by real cases. CONCLUSION: The calculation formulae are
      simple and accurate to evaluate the likelihood ratio for two individuals' genetic
      relationship with X-STR typing. The formulae provide the basic potential value
      for the difficult kinship testing with X-STR loci.

PMID- 24303760
TI  - Association of five SNPs at the PARK16 locus as a susceptibility locus with
      Parkinson's disease for forensic application.
AB  - To investigate the association of five SNPs (rs823083, rs708723, rs4951261,
      rs823076 and rs16856110) at the PARK16 locus with Parkinson's disease (PD), and
      to potentiate its forensic application. The genomic DNAs of 215 PD patients and
      212 matched controls from the northern Han Chinese population were amplified in
      two independent PCR systems and subsequently genotyped by digestion with the
      three endonucleases (Hinf I, Nco I and Msp I ). The genetic parameters and
      association studies were carried out with SPSS 13.0, Haploview version 4.2 and
      PLINK 1.07 softwares. We detected accurately all genotypes in the five SNPs with
      multiplex PCR-RFLP and mismatched multiplex PCR-RFLP techniques. The genotypes of
      four SNPs, except for rs823083, were in Hardy-Weinberg equilibrium. The four
      SNPs, rs16856110, rs4951261, rs708723 and rs823076, which were in linkage
      equilibrium, should not be associated with PD (P-values ranging from 0.077 to
      0.544). The SNPs investigated at the PARK16 locus were not found to be involved
      in PD-associated blocks in the northern Han Chinese population. The allele
      distributions of rs708723, rs4951261, rs823076 and rs16856110 in the northern Han
      Chinese population can be highly polymorphic, which can be applied to genetic
      analysis and forensic practices.

PMID- 24303761
TI  - [Forensic analysis of 24 dismembered homicide cases in Shanghai].
AB  - OBJECTIVE: To explore the characteristics of the dismembered homicide cases in
      Shanghai and to provide the valuable guidance for forensic pathological
      practices. METHODS: Twenty-four cases of dismembered homicides were selected from
      2005 to 2012 in Institute of Forensic Science, Shanghai Public Security Bureau.
      The general information of the victims and suspects, cause of death, criminal
      motive, postmortem body parts, tools and information of discarding body parts
      were retrospectively analyzed. RESULTS: Among the 24 dismembered homicide cases,
      victims were female in 16 cases, and suspects were male in 23 cases and were
      acquaintances in 22 cases. The main causes of death were mechanical asphyxia and
      traumatic brain injury. Most of the criminal motives were emotional disputes. The
      number of postmortem body parts was commonly from 20 to 30. The tools were mainly
      sharp instruments, including kitchen knives used in 20 cases. The postmortem body
      parts were discarded to different transregional areas, mainly using vehicles.
      CONCLUSION: The dismembered homicide cases in Shanghai show the following
      characteristics: the number of postmortem body parts is in large quantity; the
      methods of dismembered corpse are complex and different; the job characteristics
      of suspects are difficult to determine; the distance from homicide scene is far
      and the vehicles are commonly used.

PMID- 24303762
TI  - [Medical negligence in surgery: 112 cases retrospective analysis].
AB  - OBJECTIVE: To explore the general characteristics of medical negligence in
      surgery in order to provide the reference for forensic practices. METHODS: One
      hundred and twelve cases of medical negligence in surgical department were
      retrospectively analyzed in Fada Institute of Forensic Medicine and Science from
      2008 to 2010. RESULTS: The common types of medical negligence cases in the
      surgery were improper operation procedure (28.57%), failure of consent (26.79%),
      and inadequate monitoring (22.32%). The results of complications included
      disability or functional impairment (61.61%), death (31.25%) and transient
      impairment with no obvious adverse reactions (7.14%). The most common roles
      played by the medical negligence cases were minor role (26.79%), equal role
      (19.64%), and slight role (14.29%). CONCLUSION: Significant attention should be
      paid to the operation procedure, consent, and monitoring. It should be cautious
      to not make assessment on involvement degree of medical negligence.

PMID- 24303763
TI  - [Mutation of suspected autosomal STR loci: 227 cases retrospective analysis].
AB  - OBJECTIVE: To study the suspected autosomal STR loci mutation cases. METHODS: A
      total of 227 suspected autosomal STR loci mutation cases were selected from
      Center of Forensic Sciences, Beijing Genomics Institute. The allelic mutation
      cases were screened and the number of mutation of each STR loci was statistically
      analyzed. The CPI value was calculated in order to study the characteristics and
      rules of the mutations. RESULTS: In the 227 suspected mutation cases, 3 cases
      were excluded paternity, and 228 mutations were observed at 18 STR loci in the
      rest of the cases. The average number of STR mutation loci was 1-2. The maximum
      of mutation step was 4. After using 20A amplification kit, the CPI values in 3
      non-parentage cases were all less than 10(4). After using 20A and 10G
      amplification kits, the CPI values were all larger than 10(4) in all standard
      parents-child triplet cases and in 99.45% of diad cases. CONCLUSION: The allelic
      mutation of STR loci is relatively common in forensic cases. By increasing the
      number of the required STR loci and supplementing the samples of the triplet, the
      identification errors could be decreased to a great extent when suspected
      autosomal STR loci mutation occurs.

PMID- 24303764
TI  - [Depression status of the family member and its influencing factors in the
      patient with mental disorder caused by cerebral trauma: 245 cases analysis].
AB  - OBJECTIVE: To determine the family member's depression status and its influencing
      factors in the patient with mental disorder caused by cerebral trauma. METHODS:
      The self-designed information questionnaire and self-rating depression scale
      (SDS) were used to investigate 245 family members' depression conditions. On the
      basis of SDS score index, all cases were divided into depression group and non
      depression group. The data were analyzed by the univariate analysis and multiple
      factors regression analysis. RESULTS: In the 245 family members, 117 family
      members had different degrees of depressive symptoms including 68 with mild
      depression, 42 with moderate depression, and 7 with severe depression. In the
      multiple factors regression analysis, genetic relationship, personality
      characteristics and payment method were the main influencing factors of the
      depression status. CONCLUSION: Much attention should be paid to the family
      member's depression condition of the patient with mental disorder caused by
      cerebral trauma through specific psychological intervention.

PMID- 24303765
TI  - [Genetic polymorphisms of 15 X-STR loci in Shandong Han population].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of 15 X-STR loci in Shandong
      Han population in order to establish the forensic application database. METHODS:
      The multi-PCR primers of these loci were designed by Primer Premier 5.0 software
      and labeled by 4 fluoresceins (FAM, VIC, NED and TET). The developed multi-PCR
      was used to investigate 15 X-STR loci (DXS10011, DXS101, GATA 165B12, DXS6795,
      DXS6800, DXS6801, DXS6803, DXS7132, DXS7133, DXS7423, DXS7424, DXS8377, DXS8378,
      DXS9898 and HPRTB) selected from the X chromosome of 481 unrelated individuals
      (295 females and 186 males) in Shandong Han population. RESULTS: Among the 15 X
      STR loci, GATA 165B12, DXS6800, DXS6803, DXS7133 and DXS7423 showed moderate
      polymorphisms, while the rest 10 X-STR loci showed high polymorphisms (PIC > 0.5
      and H > 0.5). No shared haplotype was detected among the males in Shandong Han
      population. CONCLUSION: The developed multi-PCR system with fluorescence
      detection provides an effective way to establish X-STR loci database of
      population genetics in Shandong Han population and shows its forensic
      application.

PMID- 24303766
TI  - [Genetic polymorphisms of 16 non-CODIS STR loci in Beijing Han population].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of 16 non-CODIS loci (D6S477,
      D22-GATA198B05, D15S659, D8S1132, D3S3045, D17S1290, D14S608, D2S441, D18S535,
      D13S325, D10S1435, DlS2368, DIS1656, D7S3048, D10S1248 and D19S253) in Beijing
      Han population. METHODS: The DNA of 300 unrelated individuals in Beijing Han
      population were PCR amplified using GoldeneyeM DNA identification system 18NC
      kit, and the PCR products were analyzed by electrophoresis through 3130XL genetic
      analyzer. The fragment sizes of alleles were taken subsequently by GeneMapper
      v3.2. RESULTS: The distributions of genotype frequencies of 16 non-CODIS STR loci
      in Beijing Han population satisfied the Hardy-Weinberg equilibration. The
      population genetic parameters were obtained as followings: heterozygosity was
      0.677-0.873; discrimination power, 0.890-0.967; probability of paternity
      exclusion, 0.393-0.741; and polymorphism information content, 0.706-0.853.
      CONCLUSION: These 16 non-CODIS STR loci show great genetic polymorphisms in
      Beijing Han population, and are useful for the research of population genetics
      and forensic application.

PMID- 24303767
TI  - [Modified TRIzol method for RNA and DNA co-extraction from blood].
AB  - OBJECTIVE: To establish a new method for RNA and DNA co-extraction from the same
      sample by TRIzol reagent. METHODS: After the aqueous phase which contained total
      RNA was removed by traditional TRIzol method, the values of pH of the interphase
      phase and organic phase were adjusted. The DNA was precipitated with ethanol and
      purified with DNA IQ system. The purified DNA was measured in quality and
      quantity. As the template, it was amplified and typed by PCR-STR. The data was
      compared with that extracted by traditional TRIzol method. RESULTS: The DNA
      extracted by this modified method showed a better result of quality and quantity
      than that by traditional TRIzol method and a good STR typing. CONCLUSION: The
      modified TRIzol method is advisable and reliable to simultaneously extract both
      DNA and RNA from the same sample. It could be used for individual identification
      and paternity testing to satisfy the need of forensic science.

PMID- 24303768
TI  - [Development of Chinese forensic Y-STR DNA database].
AB  - Y chromosome is a male-specific paternal inherited chromosome. The STR markers on
      Y chromosome have been widely used in forensic practices. This article summarizes
      the characteristics of Y-STR and some factors are considered of selecting
      appropriate Y-STR markers for Chinese population. The prospects of existing and
      potential forensic applications of Y-STR profiles are discussed including
      familial excluding, familial searching, crowd source deducing, mixture sample
      testing, and kinship identifying. The research, development, verification of Y
      STR kit, Y-STR mutation rate, and search software are explored and some
      suggestions are given.

PMID- 24303769
TI  - [Statistical prediction methods in violence risk assessment and its application].
AB  - It is an urgent global problem how to improve the violence risk assessment. As a
      necessary part of risk assessment, statistical methods have remarkable impacts
      and effects. In this study, the predicted methods in violence risk assessment
      from the point of statistics are reviewed. The application of Logistic regression
      as the sample of multivariate statistical model, decision tree model as the
      sample of data mining technique, and neural networks model as the sample of
      artificial intelligence technology are all reviewed. This study provides data in
      order to contribute the further research of violence risk assessment.

PMID- 24303770
TI  - Optimization-based decision support to assist in logistics planning for hospital
      evacuations.
AB  - The evacuation of the hospital is a very complex process and evacuation planning
      is an important part of a hospital's emergency management plan. There are
      numerous factors that affect the evacuation plan including the nature of threat,
      availability of resources and staff the characteristics of the evacuee
      population, and risk to patients and staff. The safety and health of patients is
      of fundamental importance, but safely moving patients to alternative care
      facilities while under threat is a very challenging task. This article describes
      the logistical issues and complexities involved in planning and execution of
      hospital evacuations. Furthermore, this article provides examples of how
      optimization-based decision support tools can help evacuation planners to better
      plan for complex evacuations by providing real-world solutions to various
      evacuation scenarios.

PMID- 24303771
TI  - How much do hazard mitigation plans cost? An analysis of federal grant data.
AB  - Under the Disaster Mitigation Act of 2000 and Federal Emergency Management
      Agency's subsequent Interim Final Rule, the requirement was placed on local
      governments to author and gain approval for a Hazard Mitigation Plan (HMP) for
      the areas under their jurisdiction. Low completion percentages for HMPs--less
      than one-third of eligible governments--were found by an analysis conducted 3
      years after the final deadline for the aforementioned legislation took place.
      Follow-up studies showed little improvement at 5 and 8 years after the deadline.
      It was hypothesized that the cost of a HMP is a significant factor in determining
      whether or not a plan is completed. A study was conducted using Boolean Matrix
      Analysis methods to determine what, if any, characteristics of a certain
      community will most influence the cost of a HMP. The frequency of natural hazards
      experienced by the planning area, the number of jurisdictions participating in
      the HMEP, the population, and population density were found to significantly
      affect cost. These variables were used in a regression analysis to determine
      their predictive power for cost. It was found that along with two interaction
      terms, the variables explain approximately half the variation in HMP cost.

PMID- 24303772
TI  - Assessing the quality of state disaster recovery plans: implications for policy
      and practice.
AB  - Pre-event planning for postdisaster recovery helps to improve recovery outcomes
      following disasters by engaging the network of stakeholders involved in recovery
      and working to develop a degree of consensus around recovery priorities. States
      serve as a linchpin between local communities and federal agencies, and the
      development of comprehensive state recovery plans allows states to communicate
      recovery goals and decision-making processes. This article addresses the
      limitations of what we know about the role of the state in disaster recovery by
      describing the application of a plan quality evaluation tool to a sample of state
      recovery plans. The plans evaluated in this study tended to be heavily focused on
      federal and state programs and grants available following disasters. To
      effectively guide recovery decision-making and encourage community resilience,
      state recovery plans should help to set a direction for recovery and develop
      corresponding policies that may be implemented by the broad network of
      stakeholders involved in recovery.

PMID- 24303773
TI  - Delivering integrated HAZUS-MH flood loss analyses and flood inundation maps over
      the Web.
AB  - Catastrophic flooding is responsible for more loss of life and damages to
      property than any other natural hazard. Recently developed flood inundation
      mapping technologies make it possible to view the extent and depth of flooding on
      the land surface over the Internet; however, by themselves these technologies are
      unable to provide estimates of losses to property and infrastructure. The Federal
      Emergency Management Agency's (FEMA's) HAZUS-MH software is extensively used to
      conduct flood loss analyses in the United States, providing a nationwide database
      of population and infrastructure at risk. Unfortunately, HAZUS-MH requires a
      dedicated Geographic Information System (GIS) workstation and a trained operator,
      and analyses are not adapted for convenient delivery over the Web. This article
      describes a cooperative effort by the US Geological Survey (USGS) and FEMA to
      make HAZUS-MH output GIS and Web compatible and to integrate these data with
      digital flood inundation maps in USGS's newly developed Inundation Mapping Web
      Portal. By running the computationally intensive HAZUS-MH flood analyses offline
      and converting the output to a Web-GIS compatible format, detailed estimates of
      flood losses can now be delivered to anyone with Internet access, thus
      dramatically increasing the availability of these forecasts to local emergency
      planners and first responders.

PMID- 24303774
TI  - After Virginia Tech: an analysis of Internet and social media use in campus
      emergency preparedness.
AB  - This study gauges the degree to which the nation's colleges and universities
      learned a key lesson of the 2007 Virginia Tech tragedy: the need to rapidly
      disseminate emergency information to the campus community. A content analysis of
      162 school Web sites found that three of four contained emergency preparedness
      information. It appears that most are now prepared to use the Internet and social
      media to alert stakeholders in the event of campus crises. However, less than
      half had links to emergency/safety information on their home pages. School size
      and governance appeared to factor in its placement on each Web site.

PMID- 24303775
TI  - Development of a national sport event risk management training program for
      college command groups.
AB  - The US Department of Homeland Security identified college sport venues as
      terrorist targets due to the potential for mass casualties and catastrophic
      social and economic impact. Therefore, it is critical for college sport safety
      and security personnel to implement effective risk management practices. However,
      deficiencies have been identified in the level of preparedness of college sport
      event security personnel related to risk management training and effective
      emergency response capabilities. To address the industry need, the National
      Center for Spectator Sports Safety and Security designed, developed, and
      evaluated a national sport event risk management training program for National
      Collegiate Athletic Association command groups. The purpose of this article was
      to provide an overview of the design, development, and evaluation process.

PMID- 24303776
TI  - Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean
      population.
AB  - The heat shock 70 kDa protein 1B (HSPA1B), which has been well-studied among the
      famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases,
      including Alopecia Areata (AA). In this study, the association of a 5'
      untranslated region (5'UTR) SNP rs6457452 and a promoter SNP rs2763979 (-1140C >
      T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients.
      Statistical analyses using the multiple logistic models were done, according to
      the onset and the clinical features of AA, including the age of onset, family
      history, type of AA lesion, nail involvement and body hair involvement. The
      results showed that rs6457452 was associated with the onset of AA (p < 0.002). In
      the analysis of clinical features of AA, rs6457452 was weakly related to the age
      of onset (p <= 0.04) and that rs2763979 was only weakly related to the type of AA
      lesion (p = 0.041). In conclusion, we suggest that the 5'UTR SNP rs6457452 of
      HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may
      confer the reduced susceptibility to AA in the Korean population. 

PMID- 24303777
TI  - Three Variants of or near VEGF-A Gene are Not Associated with Neovascular Age
      Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in a Han
      Chinese Population.
AB  - PURPOSE: To investigate whether three previously identified variants for age
      related macular degeneration (AMD), the single nucleotide polymorphism (SNP)
      variants of or near the vascular endothelial growth factor A gene (VEGFA), were
      associated with neovascular AMD or polypoidal choroidal vasculopathy (PCV) in a
      Han Chinese cohort. METHODS: This was a case-control study comprising 251 PCV
      patients, 157 neovascular AMD patients, and 204 control participants in a Han
      Chinese population. The rs833069, rs943080 and rs4711751 SNP were genotyped using
      the Multiplex SNaPshot system. Genotypes and allele frequencies of patients and
      controls were evaluated for the SNPs using PLINK software. RESULTS: None of the
      allelic or genotypic effects of these three variants was significantly associated
      with PCV, neovascular AMD or combined both patient categories. CONCLUSIONS: No
      association was found to support the role for the rs833069, rs943080 and
      rs4711751 variants of or near VEGFA gene in susceptibility to either PCV or
      neovascular AMD in Han Chinese population. Further replication is necessary to
      validate these results.

PMID- 24303778
TI  - Axial Lengths in Children with Recessive Cornea Plana.
AB  - INTRODUCTION: While flat keratometry contributes to the hyperopia and associated
      refractive accommodative esotropia that is part of recessive cornea plana,
      whether or not axial lengths are abnormally short in the disease is unclear. In
      this study we assess this possibility. METHODS: Prospective (2010-2012) axial
      length measurement (IOLmaster; Carl Zeiss, Oberkochen, Germany) of affected right
      eyes and comparison to right eyes with refractive accommodative esotropia only.
      Keratometry and refraction were also performed. RESULTS: For eight affected right
      eyes (age 10-12 years; seven families) axial length ranged from 21.46-24.80 mm
      (mean 23.34). Best corrected visual acuity ranged from 20/25 to 20/50,
      keratometry from 25.33-39.80 diopters (D) [mean 31.80], and refraction from +2.00
      to +14.00 D (mean +7.22). For 50 control right eyes (age 4-12 years), axial
      length ranged from 19.87-23.66 mm (mean 21.6). Best-corrected visual acuity was
      20/25 or better, keratometry ranged from 39.81-46.25 D (mean 42.42), and
      refraction from +2.25 to +8.00 D (mean 4.71). Axial lengths were longer in the
      affected group (2-tailed unpaired t-test p value 0.000005) despite greater
      hyperopia (2-tailed unpaired t-test p value 0.001). CONCLUSIONS: Despite greater
      hyperopia, axial lengths were longer in eyes with recessive cornea plana,
      evidence that axial lengths are not shortened by the disease. Keratometry in
      children with cornea plana was below the range of controls and was the major
      factor underlying the phenotype's hyperopia.

PMID- 24303779
TI  - Effects of language dominance on item and order memory in free recall, serial
      recall and order reconstruction.
AB  - Spanish-English bilinguals (N = 144) performed free recall, serial recall and
      order reconstruction tasks in both English and Spanish. Long-term memory for both
      item and order information was worse in the less fluent language (L2) than in the
      more fluent language (L1). Item scores exhibited a stronger disadvantage for the
      L2 in serial recall than in free recall. Relative order scores were lower in the
      L2 for all three tasks, but adjusted scores for free and serial recall were
      equivalent across languages. Performance of English-speaking monolinguals (N =
      72) was comparable to bilingual performance in the L1, except that monolinguals
      had higher adjusted order scores in free recall. Bilingual performance patterns
      in the L2 were consistent with the established effects of concurrent task
      performance on these memory tests, suggesting that the cognitive resources
      required for processing words in the L2 encroach on resources needed to commit
      item and order information to memory. These findings are also consistent with a
      model in which item memory is connected to the language system, order information
      is processed by separate mechanisms and attention can be allocated differentially
      to these two systems.

PMID- 24303780
TI  - Standard and absolute pKa scales of substituted benzoic acids in room temperature
      ionic liquids.
AB  - Equilibrium acidity (pKa) scales of 15 substituted benzoic acids in four room
      temperature ionic liquids (RTILs), BmimOTf, BmimNTf2, BmpyNTf2, and Bm2imNTf2,
      were established under standard conditions using a modified indicator overlapping
      method. The effect of homo hydrogen bonding on equilibrium acidity was
      calibrated, and the derived pKa values were evidenced to be free from ion-paring
      complication. Regression analyses demonstrated that all of the pKa scales
      obtained in four RTILs are linearly correlated to each other with an R value
      better than 0.996. These scales are also correlated well with the pKa values in
      DMSO and with the corresponding gas-phase acidities with regression coefficients
      of 0.993 and 0.992, respectively. In addition, both the cation and anion of the
      ionic liquids were found to play a role in affecting the acidity of carboxylic
      acid. 

PMID- 24303781
TI  - Withanolides with phytotoxic activity from two species of the genus Salpichroa:
      S. origanifolia and S. tristis var. lehmannii.
AB  - Seven new withanolides, salpichrolides O-U (1-7), the known 2,3
      dihydrosalpichrolide B (9), a substance not previously isolated from a natural
      source, and three known compounds, salpichrolide D (8), salpichrolide A (10), and
      salpichrolide C (11), were isolated and characterized from the aerial parts of
      Salpichroa origanifolia and S. tristis var. lehmannii. Compounds 1-4 and 8 have
      an oxygenated D ring, while compounds 5-7 and 9-11 possess a six-membered
      aromatic D ring. The structures of the isolated compounds were identified by
      analysis of their spectroscopic data including NMR and MS. Withanolides 1, 3, 8,
      10, and 11 exhibited selective radicle growth inhibition toward Lactuca sativa
      (lettuce) at 150 and 400 ppm. 

PMID- 24303783
TI  - The protective role of MTR A2756G polymorphisms in childhood acute lymphoblastic
      leukemia remains inconclusive.

PMID- 24303782
TI  - Metabolomics analysis identifies d-Alanine-d-Alanine ligase as the primary lethal
      target of d-Cycloserine in mycobacteria.
AB  - d-Cycloserine is an effective second line antibiotic used as a last resort to
      treat multi (MDR)- and extensively (XDR) drug resistant strains of Mycobacterium
      tuberculosis . d-Cycloserine interferes with the formation of peptidoglycan
      biosynthesis by competitive inhibition of alanine racemase (Alr) and d-alanine-d
      alanine ligase (Ddl). Although the two enzymes are known to be inhibited, the in
      vivo lethal target is still unknown. Our NMR metabolomics work has revealed that
      Ddl is the primary target of DCS, as cell growth is inhibited when the production
      of d-alanyl-d-alanine is halted. It is shown that inhibition of Alr may
      contribute indirectly by lowering the levels of d-alanine, thus allowing DCS to
      outcompete d-alanine for Ddl binding. The NMR data also supports the possibility
      of a transamination reaction to produce d-alanine from pyruvate and glutamate,
      thereby bypassing Alr inhibition. Furthermore, the inhibition of peptidoglycan
      synthesis results in a cascading effect on cellular metabolism as there is a
      shift toward the catabolic routes to compensate for accumulation of peptidoglycan
      precursors. 

PMID- 24303784
TI  - MST1/2 and YAP1 gene expression in acute myeloid leukemia.

PMID- 24303785
TI  - Linear DNA for rapid prototyping of synthetic biological circuits in an
      Escherichia coli based TX-TL cell-free system.
AB  - Accelerating the pace of synthetic biology experiments requires new approaches
      for rapid prototyping of circuits from individual DNA regulatory elements.
      However, current testing standards require days to weeks due to cloning and in
      vivo transformation. In this work, we first characterized methods to protect
      linear DNA strands from exonuclease degradation in an Escherichia coli based
      transcription-translation cell-free system (TX-TL), as well as mechanisms of
      degradation. This enabled the use of linear DNA PCR products in TX-TL. We then
      compared expression levels and binding dynamics of different promoters on linear
      DNA and plasmid DNA. We also demonstrated assembly technology to rapidly build
      circuits entirely in vitro from separate parts. Using this strategy, we
      prototyped a four component genetic switch in under 8 h entirely in vitro. Rapid
      in vitro assembly has future applications for prototyping multiple component
      circuits if combined with predictive computational models. 

PMID- 24303786
TI  - Carbocisteine reduces virus-induced pulmonary inflammation in mice exposed to
      cigarette smoke.
AB  - Carbocisteine (S-CMC) inhibits viral infection and prevents acute exacerbation of
      chronic obstructive pulmonary disease. We recently demonstrated the protective
      effects of NF-E2-related factor (Nrf) 2 against influenza virus (FluV)-induced
      pulmonary inflammation in mice exposed to cigarette smoke (CS). In our current
      study, we investigated the effects of S-CMC on Nrf2 activation in cultured
      macrophages, and in mice infected with influenza after exposure to CS. Nuclear
      translocation of Nrf2 and the expression of Nrf2-targeted antioxidant genes, such
      as heavy and light subunits of gamma glutamyl cysteine synthetase and heme
      oxigenase-1, were enhanced in a dose-dependent manner after treatment with S-CMC
      in peritoneal and alveolar macrophages of wild-type mice, but not in those of
      Nrf2-deficient mice. Nuclear translocation of Nrf2 in macrophages was inhibited
      by the phosphatidylinositol 3-kinase inhibitor, LY294002. Phosphorylated Akt,
      Nrf2, and heme oxigenase-1 were induced in the alveolar macrophages of the lungs
      in wild-type mice after S-CMC administration. The extent of oxidative stress,
      inflammatory cell infiltration, pulmonary edema, and goblet cell hyperplasia was
      suppressed by S-CMC administration in the lungs of wild-type mice after exposure
      to both CS and FluV. Our findings suggest that S-CMC reduces pulmonary
      inflammation and mucus overproduction in mice exposed to CS after infection with
      FluV via the activation of Nrf2.

PMID- 24303787
TI  - Total synthesis of cytotoxic metabolite ( +/- )-desmethyldiaportinol from
      Ampelomyces sp.
AB  - A concise total synthesis of ( +/- )-desmethyldiaportinol isolated from
      Ampelomyces sp. is described. Microwave-assisted cyclocondensation of 3,5
      dimethoxyhomopthalic acid with 3,4-dibromobutanoyl chloride afforded the 3-(2,3
      dibromopropyl)-6, 8-dimethoxyisocoumarin in 2-3 min as the pivotal step. The 3,4
      dibromobutanoyl chloride was itself synthesised from 3-butenoic acid via
      bromination in carbon tetrachloride at room temperature to yield 3,4
      dibromobutanoic acid followed by reaction with thionyl chloride. The replacement
      of bromo- by hydroxyl substituent was achieved under mild conditions involving
      the refluxing in a mixture of acetone and water to provide ( +/- )-3-(2,3
      dihydroxypropyl)-6,8-dimethoxyisocoumarin which on complete demethylation
      furnished the title natural product.

PMID- 24303788
TI  - Assessment of pesticide residues in strawberries grown under various treatment
      regimes.
AB  - The dynamics of pesticide residues in strawberries that involved quantification
      of pesticide residues in ripe fruits after model treatment was evaluated in
      repeated field trials conducted over 3 years. Sixteen commercial pesticide
      formulations in various combinations were employed in applications from 7 to 44
      days before harvest. Altogether 21 active ingredients and some of their
      metabolites were determined in treated strawberries using LC-MS and GC-MS
      methods. Except for propargite, the concentrations of all active ingredients
      declined below the respective MRLs (Regulation (EC) No. 396/2005); nevertheless,
      most of the tested fungicides often persisted above the 0.01 mg kg-1 limit
      required by baby food producers to avoid the risk of exceeding the 'baby food
      limit' established in Commission Directive 2006/141/EC. On the other hand,
      residues of the majority of tested insecticides, namely spinosad, pymetrozine,
      deltamethrin, lambda-cyhalothrin and azadirachtin, declined below this limit.

PMID- 24303789
TI  - Recombinant protein expression in Lactococcus lactis using the P170 expression
      system.
AB  - The use of the Gram-positive bacterium Lactococcus lactis in recombinant protein
      production has several advantages, including the organism's long history of safe
      use in food production and the fact that it does not produce endotoxins.
      Furthermore the current non-dairy L. lactis production strains contain few
      proteases and can secrete stable recombinant protein to the growth medium. The
      P170 expression system used for recombinant protein production in L. lactis
      utilizes an inducible promoter, P170, which is up-regulated as lactate
      accumulates in the growth medium. We have optimised the components of the
      expression system, including improved promoter strength, signal peptides and
      isolation of production strains with increased productivity. Recombinant proteins
      are produced in a growth medium with no animal-derived components as a simple
      batch fermentation requiring minimal process control. The accumulation of lactate
      in the growth medium does, however, inhibit growth and limits the yield from
      batch and fed-batch processes. We therefore combined the P170 expression system
      with the REEDTM technology, which allows control of lactate concentration by
      electro-dialysis during fermentation. Using this combination, production of the
      Staphylococcus aureus nuclease reached 2.5 g L(-1).

PMID- 24303790
TI  - Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution,
      function and eAg-specific antibody secretion.
AB  - Studies reporting beneficial effects of B lymphocytes in autoimmune diseases have
      been accumulating and a regulatory role for certain B cell subsets is hence
      getting more and more recognition. Recently, B cells were shown to exhibit a
      regulatory effect in a T cell transfer model of colitis. Here, B cells exposed to
      enteroantigen (eAg) ex vivo abrogated the colitogenic effect if co-transplanted
      with Treg-depleted (CD4+CD25-) T cells into severe combined immune deficiency
      (SCID) mice. These data may imply a role for B cells that bind eAg (eAg+ B cells)
      in the immunopathology of colitis. Here, we report the detection of a subset of
      eAg+ B cells, including both B2 and B1 lineages, and show that these cells are
      present in all peripheral lymphoid organs of the mouse including the peritoneal
      cavity. eAg+ B cells are far more efficient as eAg-presenting cells than
      unfractionated splenocytes or eAg- B cells in causing proliferation of eAg
      specific T cells. In comparison with eAg- B cells, eAg+ B cells secrete a
      significant amount of IL-10 in vitro, suggesting an anti-inflammatory potential.
      Compared with wild-type B cells, B cell receptor (BCR) transgenic, hen egg
      lysozyme-specific B cells show inferior eAg binding and T cell stimulatory
      activity suggesting involvement of the BCR in eAg binding and processing. After
      activation of CD19(+) B cells by eAg and hybridization with hypoxanthine
      aminopterin-thymidine (HAT) sensitive *63 lymphoma cells followed by cloning at
      limiting dilution conditions, around 10% of the hybridoma cells secrete eAg
      specific antibodies.

PMID- 24303791
TI  - Molecular basis for insecticide-enhanced thermotolerance in the brown planthopper
      Nilaparvata lugens Stal (Hemiptera:Delphacidae).
AB  - Climate change is likely to have marked ecological effects on terrestrial
      ecosystems, including the activities of insect pests. Most attention has focused
      on the increasing geographical ranges of pests; however, if extrinsic factors
      enhance their thermotolerance, populations may express increased voltinism and
      longer daily and annual activity periods. These changes in pest populations have
      the potential for severe consequences, including increased crop losses and
      decreased food security at the global level. The brown planthopper (BPH)
      Nilaparvata lugens Stal (Hemiptera: Delphacidae) is a serious pest of rice crops
      in temperate and tropical regions of Asia. It is often present in rice
      microclimates at temperatures close to its maximum thermotolerance. Recent BPH
      outbreaks in tropical Asia are considered to be associated with excess use of
      pesticides and increasing temperature. This study tested whether exposure to
      sublethal concentrations of triazophos (tzp), an insecticide widely used in Asian
      rice production, enhances thermotolerance of BPH. Tzp exposure (40 ppm at 40 
      degrees C) significantly decreased mortality (from 94% in controls to 50% at 48 h
      post-treatment) and increased lethal mean time (LT50 ) of adults by 17.2 h. To
      investigate the underlying molecular mechanism of this tzp-enhanced
      thermotolerance, we selected Hsp70 and Arginine kinase (Argk) for detailed study.
      Transcripts encoding both proteins in third-instar nymphs and brachypterous adult
      females were up-regulated, compared with controls, after exposure to tzp. RNAi
      silencing of both genes demonstrated that Hsp70 and Argk are essential for
      survival and tzp-increased thermotolerance. We propose that tzp induces
      thermotolerance in BPHs by increasing the expression of genes that act in cell
      protection mechanisms. The significance of our proposal relates to the importance
      of understanding the influence of sublethal concentrations of insecticides on
      pest biology. In addition to its influence on thermotolerance, tzp also enhances
      BPH reproduction. We infer that exposure to a pesticide stressor can produce
      cross-tolerance, that is, increased tolerance to one stressor also increases
      tolerance to other stressors, including temperature. Aside from needing a better
      understanding of these effects in nature and in other pest/cropping systems, we
      suggest that pest management programmes can be improved with better understanding
      of the influences of stressors, including increased environmental temperatures
      and sublethal concentrations of insecticides, on pest biology. 

PMID- 24303792
TI  - A transmembrane serine residue in the Rot1 protein is essential for yeast cell
      viability.
AB  - Polar residues are present in TM (transmembrane) helices and may influence the
      folding or association of membrane proteins. In the present study, we use an in
      vivo approach to analyse the functional and structural roles for amino acids in
      membrane-spanning motifs using the Rot1 (reversal of Tor2 lethality 1) protein as
      a model. Rot1 is an essential membrane protein in Saccharomyces cerevisiae and it
      contains a single TM domain. An alanine insertion scanning analysis of this TM
      helix revealed that the integrity of the central domain is essential for protein
      function. We identified a critical serine residue inside the helix that plays an
      essential role in maintaining cell viability in S. cerevisiae. Replacement of the
      serine residue at position 250 with a broad variety of amino acids did not affect
      protein targeting and location, but completely disrupted protein function causing
      cell death. Interestingly, substitution of the serine residue by threonine
      resulted in sustained cell viability, demonstrating that the hydroxy group of the
      TM serine side chain plays a critical role in protein function. The results of
      the present study indicate that Rot1 needs the TM Ser250 to interact with other
      membrane components and exert its functional role, avoiding exposure of the
      serine hydrogen-bonding group at the lipid-exposed surface.

PMID- 24303793
TI  - Severe inbreeding depression and no evidence of purging in an extremely inbred
      wild species--the Chatham Island black robin.
AB  - Although evidence of inbreeding depression in wild populations is well
      established, the impact of genetic purging in the wild remains controversial. The
      contrasting effects of inbreeding depression, fixation of deleterious alleles by
      genetic drift, and the purging of deleterious alleles via natural selection mean
      that predicting fitness outcomes in populations subjected to prolonged
      bottlenecks is not straightforward. We report results from a long-term pedigree
      study of arguably the world's most inbred wild species of bird: the Chatham
      Island black robin Petroica traversi, in which conditions were ideal for purging
      to occur. Contrary to expectations, black robins showed a strong, negative
      relationship between inbreeding and juvenile survival, yielding lethal
      equivalents (2B) of 6.85. We also determined that the negative relationship
      between inbreeding and survival did not appear to be mediated by levels of
      ancestral inbreeding and may be attributed in part to unpurged lethal recessives.
      Although the black robin demographic history provided ideal conditions for
      genetic purging, our results show no clear evidence of purging in the major life
      history trait of juvenile survival. Our results also show no evidence of fixation
      of deleterious alleles in juvenile survival, but do confirm that continued high
      levels of contemporary inbreeding in a historically inbred population could lead
      to additional severe inbreeding depression. 

PMID- 24303794
TI  - Utility of speckle tracking echocardiography to characterize dysfunctional
      myocardium in patients with ischemic cardiomyopathy referred for cardiac
      resynchronization therapy.
AB  - BACKGROUND: Assessment of transmural scar at the site of latest mechanical
      activation is relevant to maximize outcomes in cardiac resynchronization therapy
      (CRT). Few studies have assessed the ability of speckle tracking echocardiography
      (STE)-derived short-axis strain to identify segmental myocardial scar, defined by
      contrast-enhanced cardiac magnetic resonance imaging (CMR), in patients referred
      for CRT. METHODS: A total of 26 patients with ischemic cardiomyopathy who
      underwent preprocedure echocardiography and CMR were studied. Extent of
      transmural scar was assessed using contrast-enhanced CMR and corresponding peak
      segmental radial and circumferential strains were derived using two-dimensional
      (2D) STE. Total left ventricle (LV) scar volume was compared with parameters of
      global strain. CRT response was defined as >15% reduction in LV end systolic
      volume (LVESV) at 6 months. RESULTS: Speckle tracking short-axis strain analysis
      was technically possible in over 90% of LV segments. Applying a segmental radial
      strain cutoff value of 10% distinguished segments with >50% scar area with a high
      negative predictive value (98%). Global longitudinal strain <-5% predicted CRT
      response. CONCLUSIONS: Two-dimensional STE offers potential to characterize
      dysfunctional myocardium and define segmental scar offering an integrated imaging
      approach to guide LV lead placement for CRT.

PMID- 24303795
TI  - Storage of bovine reproductive tissues and RNA extracts on ice for 24 h or
      repeated freeze-thaw cycles do not affect RNA integrity.
AB  - The aims of this study were to test (i) the effect of time of tissue and RNA
      extracts storage on ice and (ii) the effect of repeated freeze-thaw cycles on RNA
      integrity and gene expression of bovine reproductive tissues. Fragments of
      endometrium (ENDO), corpus luteum (CL) and ampulla (AMP) were subdivided and
      incubated for 0, 1, 3, 6, 12 or 24 h on ice. RNA extracts were incubated on ice
      for 0, 3, 12 or 24 h, or exposed to 1, 2, 4 or 6 freeze-thaw cycles. RNA
      integrity number (RIN) was estimated. Expression of progesterone receptor (PGR)
      and cyclophilin genes from RNA extracts stored on ice for 0 or 24 h, and 1 or 6
      freeze-thaw cycles was measured by qPCR. Tissue and RNA extract incubation on
      ice, and repeated freeze-thaw cycles did not affect RIN values of RNA from ENDO,
      CL or AMP. Storage on ice or exposure to freeze-thaw cycles did not affect Cq
      values for PGR or cyclophilin genes. In conclusion, neither generalized RNA
      degradation nor specific RNA degradation was affected by storage of tissue or RNA
      extracts on ice for up to 24 h, or by up to 6 freeze-thaw cycles of RNA extracts
      obtained from bovine ENDO, CL and AMP. 

PMID- 24303796
TI  - Low serum sex hormone-binding globulin is associated with nonalcoholic fatty
      liver disease in type 2 diabetic patients.
AB  - INTRODUCTION: Studies have indicated that low serum sex hormone-binding globulin
      (SHBG) and testosterone levels are associated with nonalcoholic fatty liver
      disease (NAFLD). However, it remains unclear whether an association exists
      between SHBG and NAFLD independent of testosterone. OBJECTIVE: This study was
      aimed to investigate the relationship between SHBG and both total and free
      testosterone levels with NAFLD. SUBJECTS AND MEASURES: One hundred and twenty
      patients with NAFLD and 120 age-, sex- and BMI-matched patients with non-NAFLD
      were enrolled into a case-control study. Serums SHBG, total testosterone (TT),
      liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Free
      testosterone (FT) and fatty liver index were calculated. RESULTS: Serum SHBG
      levels were significantly lower in NAFLD group than in non-NAFLD group (24.5 +/-
      11.0 vs 37.6 +/- 14.4 nm, P < 0.001). After adjustment for age, smoking status,
      alcohol use, duration of diabetes, BMI and fasting C-peptide, serum SHBG levels
      in men and women were inversely associated with NAFLD, with odds ratio (OR) and
      95% confidence interval (CI) in the forth quartile as 0.05 (0.01-0.30) and 0.25
      (0.08-0.77) compared with the first quartile (OR = 1.00). Additional adjustment
      for TT in men and FT in women did not materially alter the association. The
      relationship between serum TT (for men) and FT (for women) with NAFLD was
      attenuated and even diminished after multivariable adjustment for known risk
      factors and SHBG. CONCLUSION: Low serum SHBG levels, but not TT or FT, are
      associated with NAFLD in type 2 diabetic patients.

PMID- 24303797
TI  - The Volume Behavior of Autogenous Iliac Bone Grafts After Sinus Floor Elevation:
      A Clinical Pilot Study.
AB  - Iliac crest is still regarded as one of the most viable source of autogenous
      graft materials for extensive sinus floor elevation. Three-dimensional resorption
      behavior has to be taken into account in anticipation of the subsequent insertion
      of dental implants. We performed 3-dimensional volume measurements of the
      inserted bone transplants in 11 patients (6 women and 5 men; mean age = 2.3
      years) who underwent bilateral sinus floor elevation with autogenous iliac crest
      grafts. In order to determine the respective bone graft volumes, cone-beam
      computerized tomography studies of the maxillary sinuses were carried out
      directly after the operation (T0), as well as 3 months (T1) and 6 months (T2)
      postoperatively. The acquired DICOM (Digital Imaging and Communications in
      Medicine) data sets were evaluated using suitable analysis software. We evaluated
      statistical significance of graft volumes changes using a linear mixed model with
      the grouping factors for time, age, side, and sex with a significance level of P
      = .05. 38.9% of the initial bone graft volume, which amounted to 4.2 cm(3), was
      resorbed until T1. At T2, the average volume again decreased significantly by
      18.9 % to finally reach 1.8 cm(3). The results show neither age nor side
      dependency and apply equally to both sexes. Without functional load, iliac bone
      grafts feature low-volume stability in sinus-augmentation surgery. Further
      clinical and animal studies should be done to detect the optimal timing for
      implant placement. 

PMID- 24303798
TI  - The role of extracellular DNA in the establishment, maintenance and perpetuation
      of bacterial biofilms.
AB  - The significance of extracellular DNA (eDNA) in biofilms was overlooked until
      researchers added DNAse to a Pseudomonas aeruginosa biofilm and watched the
      biofilm disappear. Now, a decade later, the widespread importance of eDNA in
      biofilm formation is undisputed, but detailed knowledge about how it promotes
      biofilm formation and conveys antimicrobial resistance is only just starting to
      emerge. In this review, we discuss how eDNA is produced, how it aids bacterial
      adhesion, secures the structural stability of biofilms and contributes to
      antimicrobial resistance. The appearance of eDNA in biofilms is no accident: It
      is produced by active secretion or controlled cell lysis - sometimes linked to
      competence development. eDNA adsorbs to and extends from the cell surface,
      promoting adhesion to abiotic surfaces through acid-base interactions. In the
      biofilm, is it less clear how eDNA interacts with cells and matrix components. A
      few eDNA-binding biomolecules have been identified, revealing new concepts in
      biofilm formation. Being anionic, eDNA chelates cations and restricts diffusion
      of cationic antimicrobials. Furthermore, chelation of Mg(2+) triggers a genetic
      response that further increases resistance. The multifaceted role of eDNA makes
      it an attractive target to sensitize biofilms to conventional antimicrobial
      treatment or development of new strategies to combat biofilms. 

PMID- 24303799
TI  - Tucaresol down-modulation of MUC1-stimulated human mononuclear cells.
AB  - Interaction between antigen presenting cells and T lymphocytes, through receptors
      and co-stimulatory molecules present on the surface of these cells, is one of the
      key means to modulate the adaptive immune system. Tucaresol, a Schiff-base
      forming chemical, can be used as a substitute for the physiological donor of
      carbonyl groups of antigen presenting cells, which can interact with the amine
      groups of T lymphocytes to modulate the adaptive immune system. This study was
      done to determine whether tucaresol can enhance killing of cancer cells in vitro
      as well as protect non-obese diabetic severe combined immunodeficient mice from
      tumor development by mucin 1 stimulated human mononuclear cells through the
      adaptive immune system. The expected hypothesis was not supported. Percent
      specific lysis of MCF-7 tumor cells by mucin 1 stimulated human mononuclear cells
      was reduced by tucaresol. Furthermore, tucaresol abolished the protective effect
      of mucin 1 stimulated human mononuclear cells against MCF-7 breast cancer cell
      growth in non-obese diabetic severe combined immunodeficient mice. This study
      implies that tucaresol may be of use as an immunosuppressive agent. 

PMID- 24303800
TI  - Delivering evidence-based upper limb rehabilitation for children with cerebral
      palsy: barriers and enablers identified by three pediatric teams.
AB  - This study aimed to identify barriers and enablers experienced by occupational
      therapists to delivering evidence-based upper limb intervention for children with
      unilateral cerebral palsy. Semistructured interviews informed by the Theoretical
      Domains Framework were conducted with nine occupational therapists from three
      teams to ascertain barriers and enablers to implementing five evidence criteria.
      A key barrier was lack of knowledge of current evidence for upper limb therapies
      for children with unilateral cerebral palsy. Therapists were confident in
      delivering goal-directed bimanual occupational therapy, but less knowledgeable
      and skilled, and hence confident in providing constraint therapy. Strategies to
      increase dose of therapy were identified as greater use of home programs and
      group-based interventions; however, therapists indicated the need for further
      education and skill development in these areas. In order to increase the uptake
      of research evidence into practice, findings from this study will be used to
      inform context-specific, individually targeted implementation strategies.

PMID- 24303804
TI  - Inter-laboratory comparison study for pyrrolizidine alkaloids in animal feed
      using spiked and incurred material.
AB  - Pyrrolizidine alkaloids (PAs) are hepatotoxic metabolites produced by plants. PAs
      in animal feed can cause acute or chronic intoxications in animals and can be
      transferred to milk. An inter-laboratory comparison study among 12 laboratories,
      using their own methods of analysis, was conducted for the detection and
      quantification of PAs in animal feed. The participants were asked to quantify PAs
      in a blank test sample, a blank test sample to be spiked with a provided spiking
      mixture of seven PA standards, and a test sample contaminated with common
      groundsel (Senecio vulgaris). Ten of the participating laboratories used an LC
      MS/MS method, one used an LC-ToF-MS method, and one used a GC-MS method. None of
      the laboratories reported false-negative samples, while two laboratories reported
      false-positive results in the blank sample. z-scores were calculated for each
      laboratory for seven PAs in test samples B and C. z-scores varied considerably
      between laboratories for the concentrations of the free bases and less for the N
      oxides, probably due to the lower levels of the free bases as compared with the N
      oxides in the contaminated feed. Questionable or unsatisfactory results for the z
      scores were obtained for 8% of the cases for the spiked sample and for 12% of the
      incurred sample. Three laboratories scored consequently positive or negative
      results. No preferred method for quantification of PAs in feed could be
      identified within the methods used for this study due to the relatively small
      number of participants. It was concluded that this inter-laboratory study shows
      that the methods used for PA detection need further development for accurate
      estimation of PAs in contaminated feed. 

PMID- 24303801
TI  - Novel mechanism of attenuation of LPS-induced NF-kappaB activation by the heat
      shock protein 90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in human
      lung microvascular endothelial cells.
AB  - Heat shock protein (hsp) 90 inhibition attenuates NF-kappaB activation and blocks
      inflammation. However, the precise mechanism of NF-kappaB regulation by hsp90 in
      the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition
      by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-kappaB activation by
      LPS in primary human lung microvascular endothelial cells. Transcriptional
      activation of NF-kappaB was measured by luciferase reporter assay, gene
      expression by real-time RT-PCR, DNA binding of transcription factors by chromatin
      immunoprecipitation assay, protein-protein interaction by
      coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone
      acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by
      partial microccocal DNase digestion. In human lung microvascular endothelial
      cells, 17-AAG-induced degradation of IKBalpha was accomplished regardless of the
      phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block
      LPS-induced NF-kappaB nuclear translocation and DNA binding activity. Instead, 17
      AAG blocked the recruitment of the coactivator, cAMP response element binding
      protein binding protein, and prevented the assembly of a transcriptionally
      competent RNA polymerase II complex at the kappaB elements of the IKBalpha (an NF
      kappaB-responsive gene) promoter. The effect of LPS on IKBalpha mRNA expression
      was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down
      regulation of core histone H3 binding. Even though treatment with an HDAC
      inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was
      independent of HDAC. We conclude that hsp90 inhibition attenuates NF-kappaB
      transcriptional activation by preventing coactivator recruitment and nucleosome
      eviction from the target promoter in human lung endothelial cells.

PMID- 24303805
TI  - Single-electrode-based rotating triboelectric nanogenerator for harvesting energy
      from tires.
AB  - Rotational energy is abundant and widely available in our living environment.
      Harvesting ambient rotational energy has attracted great attention. In this work,
      we report a single-electrode-based rotating triboelectric nanogenerator (SR-TENG)
      for converting rotational energy into electric energy. The unique advantage of
      introducing the single-electrode TENG is to overcome the difficulty in making the
      connection in harvesting rotational energy such as from a moving and rotating
      tire/wheel. The fabricated device consists of a rotary acrylic disc with
      polytetrafluoroethylene (PTFE) blades and an Al electrode fixed on the base. The
      systematical experiments and theoretical simulations indicate that the asymmetric
      SR-TENGs exhibit much better output performances than those of the symmetric
      TENGs at the same rotation rates. The asymmetric SR-TENG with seven PTFE units at
      the rotation rate of 800 r/min can deliver a maximal output voltage of 55 V and a
      corresponding output power of 30 MUW on a load of 100 MOmega, which can directly
      light up tens of red light-emitting diodes. The SR-TENG has been utilized to
      harvest mechanical energy from rotational motion of a bicycle wheel. Furthermore,
      we demonstrated that the SR-TENG can be applied to scavenge wind energy and as a
      self-powered wind speed sensor with a sensitivity of about 0.83 V/(m/s). This
      study further expands the operation principle of a single-electrode-based TENG
      and many potential applications of TENGs for scavenging ambient rotational energy
      and as a self-powered environment monitoring sensor. 

PMID- 24303806
TI  - Characterization of glycoproteins in pancreatic cyst fluid using a high
      performance multiple lectin affinity chromatography platform.
AB  - Currently, pancreatic cancer is the fourth cause of cancer death. In 2013, it is
      estimated that ~38 460 people will die of pancreatic cancer. Early detection of
      malignant cyst (pancreatic cancer precursor) is necessary to help prevent late
      diagnosis of the tumor. In this study, we characterized glycoproteins and
      nonglycoproteins on pooled mucinous (n = 10) and nonmucinous (n = 10) pancreatic
      cyst fluid to identify "proteins of interest" to differentiate between mucinous
      cyst from nonmucinous cyst and investigate these proteins as potential biomarker
      targets. An automated multilectin affinity chromatography (M-LAC) platform was
      utilized for glycoprotein enrichment followed by nano-LC-MS/MS analysis. Spectral
      count quantitation allowed for the identification of proteins with significant
      differential levels in mucinous cysts from nonmucinous cysts of which one protein
      (periostin) was confirmed via immunoblotting. To exhaustively evaluate
      differentially expressed proteins, we used a number of proteomic tools including
      gene ontology classification, pathway and network analysis, Novoseek data mining,
      and chromosome gene mapping. Utilization of complementary proteomic tools
      revealed that several of the proteins such as mucin 6 (MUC6), bile salt-activated
      lipase (CEL), and pyruvate kinase lysozyme M1/M2 with significant differential
      expression have strong association with pancreatic cancer. Furthermore,
      chromosome gene mapping demonstrated coexpressions and colocalization of some
      proteins of interest including 14-3-3 protein epsilon (YWHAE), pigment epithelium
      derived factor (SERPINF1), and oncogene p53. 

PMID- 24303808
TI  - Caesalminaxins A-L, cassane diterpenoids from the seeds of Caesalpinia minax.
AB  - Fourteen new cassane diterpenoids, caesalminaxins A-L (1-14), and three known
      compounds were isolated from the seeds of Caesalpinia minax. Among the new
      diterpenoids, compounds 3 and 4 possess a rare spiro C/D ring system. The C-16
      epimeric mixture 1/2 has an unprecedented carbon skeleton, presumably derived
      from 3 by cleavage of the C-13-C-14 bond. Compound 5 is the first example of a
      cassane diterpenoid with a spiro A/B ring system. The structures of the compounds
      were elucidated on the basis of 1D and 2D NMR analysis, and the absolute
      configurations of 3, 4, 9, and 11 were determined by single-crystal X-ray
      crystallography. Biosynthesis pathways for 1/2, 3, and 5 are postulated.
      Compounds 4, 8, and the known bonducellpin D exhibited moderate activity against
      four tested human cancer cell lines, HepG-2, K562, HeLa, and Du145. 

PMID- 24303809
TI  - Granulocyte and monocyte adsorption apheresis for Behcet's disease in a pregnant
      woman.
AB  - We present a 39-year-old pregnant woman with Behcet's disease who was treated
      successfully with granulocyte and monocyte adsorption apheresis (GMA). There were
      no complications or adverse effects during her pregnancy and delivery. The
      neonate manifested no abnormalities. 

PMID- 24303810
TI  - Up and down or down and up? The process of change in constructive couple behavior
      during Traditional and Integrative Behavioral Couple Therapy.
AB  - Observed positive and negative spouse behavior during sessions of Traditional
      (TBCT) and Integrative Behavioral Couples Therapy (IBCT) were compared for
      couples with successful outcomes and their unsuccessful counterparts. One hundred
      and thirty-four married chronically and seriously distressed couples (on average
      in their forties and 80% Caucasian) were randomly assigned to TBCT or IBCT.
      Trained observers made ratings of 1224 segments from approximately 956 sessions
      sampled from the course of up to 26 sessions. Multilevel modeling was used to
      examine change over time. TBCT treatment responders demonstrated a boost-drop
      pattern, increasing in constructive behaviors early (more positive behaviors and
      less negative behaviors) but decreasing later. IBCT responders demonstrated an
      opposite, drop-boost pattern, decreasing in constructive behaviors early and
      increasing later. Patterns were significant for positive behaviors (p < .05) and
      approached significance for negative behaviors (p = .05). In both treatments,
      nonresponders showed a significant pattern of decline in positive and increase in
      negative behaviors over time, although a trend (p = .05) indicates that TBCT
      nonresponders initially declined in negative behaviors. This study helps clarify
      the different process of change in two behavioral couple therapies, which may
      assist in treatment development and provide a guide for therapists in considering
      behavioral markers of change during treatment.

PMID- 24303812
TI  - The intensity of selection acting on the couch potato gene--spatial-temporal
      variation in a diapause cline.
AB  - Cosmopolitan populations of Drosophila melanogaster have co-opted a form of
      reproductive diapause to overwinter in northern populations. Polymorphism in the
      couch potato gene has been implicated in genetic variation for this diapause
      trait. Using a collection of 20 populations from Florida to Canada and 11
      collections from 3 years in a Pennsylvania orchard, we estimated the allele
      frequencies for 15 single nucleotide polymorphisms (SNPs) in the couch potato
      gene. These include the specific polymorphism associated with diapause
      inducability. We find that the SNP polymorphism, 48034(A/T), is correlated with
      latitude and its frequencies are predicted by the incidence of diapause trait. We
      find that the clinal patterns for cpo SNPs sampled in 1997 are similar to the
      same SNPs sampled in 2009-2010. SNPs that show apparent associations with cpo
      expression are also clinal with the low-expression allele increasing in
      frequency, as would be predicted from functional knockout studies of cpo.
      Finally, we see a significant pattern where the frequency of the diapause-causing
      allele drops in frequency during the summer season, consistent with the drop in
      the incidence of the diapause trait. The selection required to drive this
      response is large, roughly 24% to 59% per generation depending on the degree of
      dominance. 

PMID- 24303811
TI  - A spectroscopic and theoretical investigation of a free-base meso
      trithienylcorrole.
AB  - The unique optical properties of free-base meso-tris(5-methylthien-2-yl)corrole
      were compared to those of the widely investigated meso-triphenyl-substituted
      analogue. A combination of spectroscopic and computational experiments was
      undertaken to elucidate the relationship between structural features of the
      neutral, mono-anionic and mono-cationic forms of the corroles and their
      corresponding optical properties. A general bathochromic shift was measured for
      the thienyl-substituted corrole. The experimental spectra are supported by
      excited state calculations. A systematic series of ground state minimizations
      were performed to determine energy minima for the flexible and solvent-sensitive
      molecules. Trithienylcorrole was found to have a more nonplanar macrocycle in
      conjunction with a high degree of pi-overlap with the meso-substituents. Both
      structural features contribute to their bathochromically shifted optical spectra.
      The configurational character of the thienyl-substituted corrole is shown to have
      a larger degree of molecular orbital mixing and doubly excited character, which
      suggest a more complex electronic structure that does not fully adhere to the
      Gouterman four-orbital model. The reactivity of the thienyl groups, particularly
      with respect to their ability to be (electro)-polymerized, combined with the
      tight coupling of the meso-thienyl groups with the corrole chromophore elucidated
      in this work, recommends the meso-thienylcorroles as building blocks in, for
      instance, organic semiconductor devices. 

PMID- 24303813
TI  - The shadow within: a colossal left atrium.

PMID- 24303814
TI  - Flutamide influences placental aldo-keto reductase family 1 member C1 (AKR1C1)
      expression in pigs.
AB  - Aldo-keto reductase family 1 member C1 (AKR1C1) catalyses the conversion of
      progesterone into inactive 20alpha-dihydroxyprogesterone. It is suggested that
      AKR1C1 expression in the placenta prevents from the cytotoxic effect of
      progesterone on foetuses during late pregnancy. The aim of the study was to
      determine whether the anti-androgen flutamide administered during late pregnancy
      (83-89 days of gestation) or before parturition (101-107 days of gestation)
      influences AKR1C1 expression in the porcine placenta. AKR1C1 mRNA and protein
      levels were measured using real-time PCR and western blotting, respectively.
      Immunolocalization of AKR1C1 within placentas was also performed. Flutamide
      significantly increased AKR1C1 mRNA (p = 0.008) and protein (p = 0.019)
      expression only during the pre-parturient period in pigs. AKR1C1 protein was
      immunolocalized in the epithelial and stromal cells of foetal and maternal part
      of placenta at both stages of gestation. Following flutamide treatment, the
      intensity of staining was higher (p = 0.045) on day 108 of gestation. In
      conclusion, porcine placental AKR1C1 expression seems to be regulated by an
      androgen signalling pathway and may be involved in foetal survival by preventing
      the detrimental effect of progesterone. 

PMID- 24303816
TI  - Pitfalls in the diagnosis and differential diagnosis of Cushing's syndrome.

PMID- 24303815
TI  - Identification of four novel serum protein biomarkers in sepsis patients encoded
      by target genes of sepsis-related miRNAs.
AB  - The goal of the present study was to identify novel protein biomarkers from the
      target genes of six serum miRNAs that we identified previously in patients with
      sepsis. The target genes were predicted by bioinformatics analysis; the levels of
      the respective proteins in the sera of patients with sepsis were detected by
      ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH
      (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity
      phosphatase 3) were predicted to be the targets of the six miRNAs, and their
      encoded proteins were used for biomarker identification. Levels of ACVR2A
      (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls,
      patients with sepsis, patients with severe sepsis and patients with septic shock.
      Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4
      (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3
      levels were not significantly different between any groups. Conjoin analysis of
      the four differentially expressed proteins showed that the area under the curve
      of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785
      0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and
      APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the
      value of predictive probabilities was 0.449, the four proteins yielded a
      sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and
      IHH levels showed differential expression between survivors and non-survivors at
      all time points. On the basis of a combined analysis of the four identified
      proteins, their predictive value of 28-day mortality of patients with sepsis was
      better than the SOFA or APACHE II scores. 

PMID- 24303817
TI  - Fractures of the proximal humerus.
AB  - Fractures of the proximal humerus have been diagnosed and managed since the
      earliest known surgical texts. For more than four millennia the preferred
      treatment was forceful traction, closed reduction, and immobilization with linen
      soaked in combinations of oil, honey, alum, wine, or cerate. The bandages were
      further supported by splints made of wood or coarse grass. Healing was expected
      in forty days. Different fracture patterns have been discussed and classified
      since Ancient Greece. Current classification of proximal humeral fractures mainly
      relies on the classifications proposed by Charles Neer and the AO/OTA
      classification. Since the late 1980's it has been known that intra- and inter
      observer variation was high within the two systems. I conducted a series of
      observer studies to qualify the disagreement further and to study to what extent
      improvement of agreement could be obtained. No clinically significant differences
      in observer agreement were found at different levels of clinical experience, by
      reducing the number of categories, or by adding high quality radiographs, CT or
      3D CT scans. A consistently low agreement on the Neer classification within and
      between untrained orthopaedic doctors was found. However, we also found that
      inter-observer agreement on treatment recommendation was higher than the
      agreement on the Neer classification. In a randomized trial we found that
      agreement could improve significantly by training of doctors, especially among
      specialists. However, classification of proximal humeral fractures remains a
      challenge for the conduct, reporting, and interpretation of clinical trials. The
      evidence for the benefits of surgery in complex fractures of the proximal humerus
      is weak. In three systematic reviews I studied the outcome after locking plate
      osteosynthesis or reverse arthroplasty in complex fractures patterns. No
      randomized trials or well-conducted comparative studies were identified. High
      failure rates suggest that the use of these implants for complex fractures of the
      humerus should not be used outside clinical protocols. I recommend the conduct of
      randomized trials, and a design of such study is proposed.

PMID- 24303818
TI  - Introduction to the special issue: community living and participation.

PMID- 24303819
TI  - System and individual outcomes and their predictors in services and support for
      people with IDD.
AB  - The growth and advancement of community-based services for people with
      intellectual and developmental disabilities (IDD) have resulted in vast changes
      in the long-term services and support landscape as well as in expected outcomes
      of service systems for service recipients. Investments in IDD research have been
      made to provide a deeper understanding of these outcomes and to explain them.
      This article summarizes outcomes and their predictors through systems and
      individual lenses by examining the research and findings of the Administration on
      Intellectual and Developmental Disabilities' Data Projects of National
      Significance that address residential services, employment services, costs of
      services, and individual outcomes. The article also discusses challenges and
      debates associated with outcome-related research and poses future research
      questions.

PMID- 24303820
TI  - Quality of life indicators for individuals with intellectual disabilities:
      extending current practice.
AB  - Quality of life is a social construct that is measured by what are considered to
      be its most appropriate indicators. Quality of life measurement in intellectual
      disability reflects a variety of indicators, often grouped under life domains.
      Subjective and objective methods of measuring indicators each have strengths and
      drawbacks, but it is currently considered best to use both methods. Indicators of
      quality of life that are common to all people have been measured to date,
      although indicators that are unique to individuals are highly useful for
      enhancing individual development and for applying person-centered practice.
      Aggregate quality of life data from individuals may not always be the best source
      of information for evaluating policies and service practices. A case is made for
      supplementing quality of life frameworks or adopting other frameworks for these
      purposes, with the Capabilities Framework offered as an example. Further, an
      argument is made that a pragmatic approach might best be taken to policy and
      program evaluation, whereby the key criterion for using a conceptual framework
      and set of indicators is its usefulness in effecting positive change in people's
      lives.

PMID- 24303821
TI  - Issues concerning self-report data and population-based data sets involving
      people with intellectual disabilities.
AB  - This article examines two methodological issues regarding ways of obtaining and
      analyzing outcome data for people with intellectual disabilities: (a) self-report
      and proxy-report data and (b) analysis of population-based data sets. Some people
      with intellectual disabilities have difficulties with self-reporting due to
      problems of understanding and communication. However, there are serious doubts
      about the validity of proxy data for subjective issues. One important challenge
      with secondary analysis of population-based data sets is the difficulty of
      accurately identifying survey participants with intellectual disabilities. In
      both areas examined, it is important to recognize these constraints when
      interpreting research based on such data.

PMID- 24303822
TI  - Families of individuals with intellectual and developmental disabilities: policy,
      funding, services, and experiences.
AB  - Families are critical in the provision of lifelong support to individuals with
      intellectual and developmental disabilities (IDD). Today, more people with IDD
      receive long-term services and supports while living with their families. Thus,
      it is important that researchers, practitioners, and policy makers understand how
      to best support families who provide at-home support to children and adults with
      IDD. This article summarizes (a) the status of research regarding the support of
      families who provide support at home to individuals with IDD, (b) present points
      of concern regarding supports for these families, and (c) associated future
      research priorities related to supporting families.

PMID- 24303823
TI  - Social inclusion and community participation of individuals with
      intellectual/developmental disabilities.
AB  - As more individuals with intellectual/developmental disabilities are physically
      included in community life, in schools, neighborhoods, jobs, recreation, and
      congregations, the challenge of going beyond physical inclusion to true social
      inclusion becomes more apparent. This article summarizes the status of the
      research about community participation and social inclusion, summarizes some
      debates and points of contention, notes emerging research issues, and highlights
      needed areas of research. It is clear that most research on these topics has been
      conducted with individuals who are in paid formal services, and there are great
      needs for understanding the community participation of individuals who live on
      their own or with their families, as well as researching social inclusion by
      focusing on the attitudes and experiences of community members themselves, not
      just individuals with disabilities and paid providers.

PMID- 24303824
TI  - The state of the science of employment and economic self-sufficiency for people
      with intellectual and developmental disabilities.
AB  - Employment, career advancement, and financial independence are highly valued in
      the United States. As expectations, they are often instilled at a young age and
      incentivized throughout adulthood. Despite their importance, employment and
      economic sufficiency continue to be out of reach for most people with
      intellectual and developmental disabilities (IDD). Over the last quarter century,
      extensive research and effort has been committed to understanding and improving
      these phenomena. This paper summarizes this employment research base by reviewing
      the literature on the effectiveness of the current employment support system,
      employment-specific interventions, and the economics and cost benefits of
      employment for people with IDD. Recommendations and directions for future
      research are also presented.

PMID- 24303826
TI  - Self-determination and choice.
AB  - Promoting self-determination and choice opportunities for people with
      intellectual and developmental disabilities has become best practice in the
      field. This article reviews the research and development activities conducted by
      the authors over the past several decades and provides a synthesis of the
      knowledge in the field pertaining to efforts to promote self-determination and
      choice.

PMID- 24303825
TI  - The state of the science of health and wellness for adults with intellectual and
      developmental disabilities.
AB  - Historically, people with intellectual and developmental disabilities (IDD) have
      experienced health disparities related to several factors including: a lack of
      access to high quality medical care, inadequate preparation of health care
      providers to meet their needs, the social determinants of health (e.g., poverty,
      race and gender), and the failure to include people with IDD in public health
      efforts and other prevention activities. Over the past decade, a greater effort
      has been made to both identify and begin to address myriad health disparities
      experienced by people with IDD through a variety of activities including programs
      that address health lifestyles and greater attention to the training of health
      care providers. Gaps in the literature include the lack of intervention trials,
      replications of successful approaches, and data that allow for better comparisons
      between people with IDD and without IDD living in the same communities.
      Implications for future research needed to reduce health disparities for people
      with IDD include: better monitoring and treatment for chronic conditions common
      in the general population that are also experienced by people with IDD, an
      enhanced understanding of how to promote health among those in the IDD population
      who are aging, addressing the health needs of people with IDD who are not part of
      the disability service system, developing a better understanding of how to
      include people with IDD in health and wellness programs, and improving methods
      for addressing the health care needs of members of this group in an efficient and
      cost-effective manner, either through better access to general medical care or
      specialized programs.

PMID- 24303827
TI  - Using research evidence to inform public policy decisions.
AB  - The application of scientific data in the development and implementation of sound
      public policy is a well-established practice, but there appears to be less
      consensus on the nature of the strategies that can and should be used to
      incorporate research data into policy decisions. This paper describes the promise
      and the challenges of using research evidence to inform public policy. Most
      specifically, we demonstrate how the application of a large-scale data set, the
      National Core Indicators (NCI), can be systematically used to drive state-level
      policy decisions, and we describe a case example of one state's application of
      NCI data to make significant changes to its Intellectual and Developmental
      Disabilities waiver. The need for continued research in this area is highlighted.

PMID- 24303828
TI  - Community living and participation: embracing the complexity and forging forward.

PMID- 24303831
TI  - Understanding opioid tolerance: a seriously overestimated phenomenon.

PMID- 24303832
TI  - The controversy over urine drug testing in pain management patient monitoring.

PMID- 24303833
TI  - Mexican perspectives on adverse events in healthcare and pain management.
AB  - Adverse events due to medical staff errors are a leading cause of morbidity and
      mortality around the world. One important aspect of this serious public health
      issue is mismanagement of pain, particularly pain associated to acute coronary
      events or cancer. In recent years, there has been increased awareness among
      international heath care communities on the importance of recognizing and
      reducing the mistakes committed on a daily basis in practically all medical
      settings. Unfortunately, most investigation and prevention programs are not
      designed around any theoretical framework on human error. Mistakes are rarely
      seen as a symptom of a larger problem. Rather than seeking to correct the root
      cause, the majority of situations are resolved on a case-by-case basis making it
      difficult to establish a cohesive prevention system. We suggest that future
      efforts should place emphasis on developing a uniform method of error detection
      and prevention, as well as improving and maintaining the patient-physician
      relationship. Medical education should be valued over litigation.

PMID- 24303834
TI  - The impact of an aging population on palliative care.
AB  - By 2050, it is predicted that 26% of the population will be aged 80 and over.
      Although older people have much to contribute, one challenging aspect of an aging
      population is the increasing rate of dementia. Palliative care is now included as
      part of the care pathway of a wide variety of nonmalignant diseases. The European
      Association for Palliative Care (EAPC) and the European Union Geriatric Medicine
      Society (EUGMS) have jointly called for every older citizen with chronic disease
      to be offered the best possible palliative care approach wherever they are cared
      for. This report is adapted from paineurope 2013; Issue 2, (c)Haymarket Medical
      Publications Ltd., and is presented with permission. paineurope is provided as a
      service to pain management by Mundipharma International LTD. and is distributed
      free of charge to healthcare professionals in Europe. Archival issues can be
      accessed via the website: http://www.paineurope.com at which European health
      professionals can register online to receive copies of the quarterly publication.

PMID- 24303835
TI  - Defining opioid tolerance and dependency.
AB  - This report is adapted from paineurope 2013; Issue 2, (c)Haymarket Medical
      Publications Ltd., and is presented with permission. paineurope is provided as a
      service to pain management by Mundipharma International, LTD. and is distributed
      free of charge to healthcare professionals in Europe. Archival issues can be
      accessed via the website: http://www.paineurope.com at which European health
      professionals can register online to receive copies of the quarterly publication.

PMID- 24303836
TI  - Managing a chronic pain patient in the perioperative period.
AB  - The chronic pain patient with and without chronic opioid medication is at risk
      for under- and overtreatment perioperatively. Careful planning of the
      perioperative period by the anesthesiologist, the pain service and the surgeon is
      crucial. Epidural analgesia requires reduction of preoperative opioid doses to a
      maximum of 50% to avoid withdrawal as well as continuous postanesthesia care unit
      monitoring for the first 24 hours. Brief cognitive behavioral interventions pre-
      and postoperatively contribute to successful pain management. The perioperative
      period may be used to re-evaluate the patient's opioid requirements. A follow-up
      by an experienced pain management service should be available after discharge of
      the chronic pain patient. Individualized assessment by a pain management team is
      necessary for this increasing group of patients. This report is adapted from
      paineurope 2013; Issue 2, (c)Haymarket Medical Publications Ltd., and is
      presented with permission. paineurope is provided as a service to pain management
      by Mundipharma International, LTD. and is distributed free of charge to
      healthcare professionals in Europe. Archival issues can be accessed via the
      website: http://www.paineurope.com at which European health professionals can
      register online to receive copies of the quarterly publication.

PMID- 24303837
TI  - Pain management discussion forum.
AB  - A query and response address comparative chronic pain management in European
      countries and the availability of psychotherapy services in pain management. This
      report is adapted from paineurope 2013; Issue 2, (c)Haymarket Medical
      Publications Ltd., and is presented with permission. paineurope is provided as a
      service to pain management by Mundipharma International LTD. and is distributed
      free of charge to healthcare professionals in Europe. Archival issues can be
      accessed via the website: http://www.paineurope.com at which European health
      professionals can register online to receive copies of the quarterly publication.

PMID- 24303839
TI  - Dicer in immune cell development and function.
AB  - Dicer is an enzyme of the RNase III endoribonuclease family, which is crucial for
      RNA interference (RNAi) in eukaryotes. Dicer is a component of the protein
      machinery (the RNA Induced Silencing Complex [RISC]) which is involved in
      catalyzing the formation of mature microRNAs from their precursors in the process
      of microRNA biogenesis. RISC-associated microRNAs bind to specific sequences in
      the 3' untranslated region of cognate mRNAs largely through complementary base
      pairing, resulting in either translational inhibition and/or the degradation of a
      specific mRNA pool. MicroRNAs epigenetically regulate the cellular levels of
      receptors, transcription factors and signaling proteins that govern the
      developmental pathways and functions of multiple cellular processes. The pivotal
      role played by Dicer in microRNA formation has also piqued the interest of
      molecular immunologists who have sought to understand the biological relevance of
      microRNAs in the development and function of the immune system. Here, we review
      the major findings of these studies and provide an overview of the role of Dicer
      and microRNAs in immune cell development and function. Additionally, we highlight
      deficiencies in our knowledge and new research areas that may enhance our
      understanding of the role of Dicer and microRNAs in immunity. 

PMID- 24303841
TI  - N,N-dimethylpiperidinium (mepiquat): Part 1. Formation in model systems and
      relevance to roasted food products.
AB  - This preliminary study reports for the first time the formation of N,N
      dimethylpiperidinium (also termed mepiquat, a plant growth regulator used widely
      on cereal crops) by Maillard-driven degradation of lysine under dry thermal
      conditions and in the presence of the naturally occurring alkaloid trigonelline.
      The heat treatment was carried out at 240 degrees C, and the resulting samples
      were analysed by liquid chromatography coupled to a high-resolution mass
      spectrometer (LC-HRMS) operating based upon Orbitrap technology. Results
      confirmed that lysine undergoes cyclisation by decarboxylative deamination in the
      presence of a carbonyl source (e.g. reducing sugars) to yield piperidine.
      Moreover, methyl rearrangement in the presence of trigonelline and under typical
      temperatures of roasting generates detectable amounts of mepiquat, identified by
      detailed mass fragmentation studies. The essential role of lysine in the
      formation of mepiquat was confirmed in a model system using (13)C6-lysine, which
      showed the expected incorporation of five (13)C atoms into the mepiquat nitrogen
      heterocycle. These findings are relevant to the potential occurrence of mepiquat
      in roasted products such as coffee and cereals.

PMID- 24303840
TI  - Inter-alpha-inhibitor blocks epithelial sodium channel activation and decreases
      nasal potential differences in DeltaF508 mice.
AB  - Increased activity of lung epithelial sodium channels (ENaCs) contributes to the
      pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial
      lining fluid reabsorption. Inter-alpha-inhibitor (IalphaI), a serum protease
      inhibitor, may decrease ENaC activity by preventing its cleavage by serine
      proteases. High concentrations of IalphaI were detected in the bronchoalveolar
      lavage fluid (BALF) of children with CF and lower airway diseases. IalphaI
      decreased amiloride-sensitive (IENaC) but not cAMP-activated Cl(-) currents
      across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in
      primary culture by 45 and 25%, respectively. Changes in IENaC by IalphaI in ATII
      cells were accompanied by increased levels of uncleaved (immature) surface alpha
      ENaC. IalphaI increased airway surface liquid depth overlying murine nasal
      epithelial cells to the same extent as amiloride, consistent with ENaC
      inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine
      at position 508 (?F508), or CF transmembrane conductance regulator knockout mice
      with IalphaI for 3 hours decreased the open probability of their ENaC channels by
      50%. ?F508 mice had considerably higher levels the amiloride-sensitive fractions
      of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only
      background levels of IalphaI in their BALF. A single intranasal instillation of
      IalphaI decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show
      that IalphaI is present in the BALF of children with CF, is an effective
      inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial
      cells of ?F508 mice.

PMID- 24303843
TI  - Brugada phenocopy with a flecainide overdose: a pharmacological dose effect?

PMID- 24303842
TI  - A targeted in vivo SILAC approach for quantification of drug metabolism enzymes:
      regulation by the constitutive androstane receptor.
AB  - The modulation of drug metabolism enzyme (DME) expression by therapeutic agents
      is a central mechanism of drug-drug interaction and should be assessed as early
      as possible in preclinical drug development. Direct measurement of DME levels is
      typically achieved by Western blotting, qPCR, or microarray, but these techniques
      have their limitations; antibody cross-reactivity among highly homologous
      subfamilies creates ambiguity, while discordance between mRNA and protein
      expression undermines observations. The aim of this study was to design a simple
      targeted workflow by combining in vivo SILAC and label-free proteomics approaches
      for quantification of DMEs in mouse liver, facilitating a rapid and comprehensive
      evaluation of metabolic potential at the protein level. A total of 197 peptides,
      representing 51 Phase I and Phase II DMEs, were quantified by LC-MS/MS using
      targeted high resolution single ion monitoring (tHR/SIM) with a defined mass-to
      charge and retention time window for each peptide. In a constitutive androstane
      receptor (Car) activated mouse model, comparison of tHR/SIM-in vivo SILAC with
      Western blotting for analysis of the expression of cytochromes P450 was
      favorable, with agreement in fold-change values between methods. The tHR/SIM-in
      vivo SILAC approach therefore permits the robust analysis of multiple DME in a
      single protein sample, with clear utility for the assessment of the drug-drug
      interaction potential of candidate therapeutic compounds. 

PMID- 24303844
TI  - Structure-activity relationships of retro-dihydrochalcones isolated from Tacca
      sp.
AB  - Several biologically active compounds have been identified from Tacca species,
      including glycosides, diarylheptanoids, saponins, withanolides, and the
      taccalonolide class of microtubule stabilizers. More recently, two cytotoxic
      retro-dihydrochalcones named evelynin A (7) and taccabulin A (6) were isolated
      and their biological activities characterized, including the finding that
      taccabulin has microtubule destabilizing effects. Here we describe the
      identification and characterization of five new retro-chalcones, named
      taccabulins B-E (1-4) and evelynin B (5) from Tacca sp. extracts. Their
      structures were determined using 1D and 2D NMR as well as mass spectroscopic data
      and modeled into the colchicine binding site of tubulin. The antiproliferative
      and microtubule effects of each compound were determined experimentally and found
      to be well correlated with modeling studies. The isolation and biological
      characterization of several retro-dihydrochalcones facilitated preliminary
      structure-activity relationships for this compound class concerning its
      antiproliferative and microtubule depolymerizing activities. 

PMID- 24303845
TI  - Direct observation of heterogeneous amyloid fibril growth kinetics via two-color
      super-resolution microscopy.
AB  - The self-assembly of normally soluble proteins into fibrillar amyloid structures
      is associated with a range of neurodegenerative disorders, such as Parkinson's
      and Alzheimer's diseases. In the present study, we show that specific events in
      the kinetics of the complex, multistep aggregation process of one such protein,
      alpha-synuclein, whose aggregation is a characteristic hallmark of Parkinson's
      disease, can be followed at the molecular level using optical super-resolution
      microscopy. We have explored in particular the elongation of preformed alpha
      synuclein fibrils; using two-color single-molecule localization microscopy we are
      able to provide conclusive evidence that the elongation proceeds from both ends
      of the fibril seeds. Furthermore, the technique reveals a large heterogeneity in
      the growth rates of individual fibrils; some fibrils exhibit no detectable
      growth, whereas others extend to more than ten times their original length within
      hours. These large variations in the growth kinetics can be attributed to fibril
      structural polymorphism. Our technique offers new capabilities in the study of
      amyloid growth dynamics at the molecular level and is readily translated to the
      study of the self-assembly of other nanostructures. 

PMID- 24303846
TI  - Predominance of IncL/M and IncF plasmid types among CTX-M-ESBL-producing
      Escherichia coli and Klebsiella pneumoniae in Bulgarian hospitals.
AB  - Our objective was to investigate the plasmid replicon-types involved in spread of
      ESBLs among Bulgarian Klebsiella pneumoniae and Escherichia coli. Sixty-three
      isolates, with transferable beta-lactam resistance determinants, collected
      between 2007 and 2009 in six medical institutions, were analysed with respect to
      their antimicrobial susceptibility, ESBL-, RAPD-, and plasmid replicon-type.
      Phylogenetic typing and screening for the O25b-ST131 lineage were carried out for
      E. coli. The predominant ESBLs were CTX-M-15 (81%) among E. coli and CTX-M-3
      (58%) among K. pneumoniae. Other sporadically found ESBLs were SHV-12 and TEM
      139, and for the first time in Bulgaria, CTX-M-1 and CTX-M-14. Replicon typing
      revealed that plasmids carrying blaCTX-M-3 exclusively belonged to IncL/M-type,
      while blaCTX-M-15 was predominantly (94%) associated with IncF-type plasmids.
      Among E. coli, 59% of the isolates were clonally related. Isolates of that
      cluster produced CTX-M-15, belonged to the O25b-ST131 lineage, predominantly
      harboured plasmids with the FIA replicon, and were found in five centres. Among
      CTX-M-3-producing K. pneumoniae, two prevailing RAPD-types were found, one
      remained restricted to one centre and the second was found in three centres. The
      incompatibility groups IncN and IncA/C linked with blaSHV-12 respectively blaTEM
      139 were found only once. To the best of our knowledge, this is the first
      detailed investigation of plasmids carrying ESBL genes among Bulgarian isolates
      demonstrating wide distribution of conjugative IncF plasmids among CTX-M-15
      producing E. coli and IncL/M plasmids among CTX-M-3 positive K. pneumoniae
      isolates.

PMID- 24303847
TI  - Case of immunoglobulin G4-related skin disease: possible immunoglobulin G4
      related skin disease cases in cutaneous pseudolymphoma only by
      immunohistochemical analysis.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized disease
      characterized by elevated serum IgG4 levels, tissue infiltration rich in IgG4(+)
      plasma cells. We report on a case which was first considered as pseudolymphoma
      from the histopathological analysis, but finally diagnosed as IgG4-related skin
      lesions. As the morphological features of cutaneous involvement of IgG4-RD are
      consistent with those of cutaneous pseudolymphoma, we tried immunostaining past
      potential cases of IgG4-RD. Thirty-two skin specimens (15 men and 17 women; mean
      age, 53 years) diagnosed as having pseudolymphoma were retrieved from the
      archives to conduct hematoxylin-eosin, IgG and IgG4 staining. Out of the 32 cases
      of cutaneous pseudolymphoma, germinal center formation was seen in 22 cases, and
      moderate-severe fibrosis was seen in seven cases. Eleven cases showed more than
      10 IgG4(+) plasma cell infiltration/high-power field, and among these 11 cases,
      seven cases (22%) showed A ratio of IgG4(+)/IgG(+) cells of more than 40%. Thus,
      out of the 32 cases of cutaneous pseudolymphomas, two cases (6.3%) satisfied IgG4
      RD histopathological diagnostic criteria. As clinical presentations and
      histopathological features of skin involvement of IgG4-RD are analogous to
      cutaneous B-cell pseudolymphoma, careful identification is required through
      systemic examination, serum IgG4 measurement and other means.

PMID- 24303848
TI  - Children's and adults' understanding of the impact of nutrition on biological and
      psychological processes.
AB  - Four studies examined children's and adults' beliefs about the impact of
      nutrition on growth and mood states. In Studies 1 and 2, 271 participants
      (preschoolers through adults) judged the impact of healthy and unhealthy
      nutrition on height and weight. In Studies 3 and 4, 267 participants judged the
      impact of healthy and unhealthy nutrition on positive and negative mood states.
      The results suggest that young children demonstrate a co-existence of an
      ontologically distinct theory of biology as well as a theory of cross-domain
      interaction when reasoning about the impact of food on biological and
      psychological processes. 

PMID- 24303849
TI  - Enzyme activity and structural dynamics linked to micelle formation: a
      fluorescence anisotropy and ESR study.
AB  - Activities of the enzymes, protease subtilisin and horse radish peroxidase (HRP)
      have been increased 50 and 40%, respectively, in the presence of the nonionic
      surfactant, alkyl polyglucoside, compared with the activities in buffer alone.
      This enzyme hyperactivity reaches a peak at 3.0 mm of surfactant. Investigation
      into the structure of surfactant aggregates indicates "giant" micelle
      superstructures at this range of surfactant concentration of 1.7 MUm in diameter-
      dramatically decreasing to 60 and 70 nm at higher surfactant concentrations,
      while surface tension measurements indicate two critical micelle concentration
      inflection points at 0.2 and 5.0 mm, which suggests transitions in micelle
      structure with respect to concentration. Furthermore, electron spin resonance
      (ESR) indicates that the micelles in first critical micelle concentration regime
      are loosely packed relative to the second aggregate phase. We hypothesize that
      this loose packing results in diminished hydration shell repulsion between the
      micelles, leading to the large, micrometer-sized aggregates. We further
      hypothesize that it is the interaction with these loosely packed micelles that
      affects the flexibility of the HRP and protease enzyme structure. Time-resolved
      fluorescence anisotropy of subtilisin in Brij-30 indicates increasing flexibility
      of catalytic active site with surfactant concentration. This is correlated with
      an increase in enzymatic activity.

PMID- 24303850
TI  - Does a 2.5-year self-management education and support intervention change
      patterns of healthcare use in African-American adults with type 2 diabetes?
AB  - AIMS: To investigate the impact of a 2.5-year diabetes self-management education
      and support intervention on healthcare use and to examine factors associated with
      patterns of healthcare use. METHODS: We recruited 60 African-American adults with
      type 2 diabetes who completed a 2.5-year empowerment-based diabetes self
      management education and support intervention. Primary healthcare use outcomes
      included acute care visits, non-acute care visits and days lost to disability.
      Acute care was a composite score calculated from the frequency of urgent care
      visits, emergency department visits and hospitalizations. Non-acute care measured
      the frequency of scheduled outpatient visits. To examine change in patterns of
      healthcare use, we compared the frequency of healthcare visits over the 6-month
      period preceding the intervention with that in the last 6 months of the
      intervention. RESULTS: No significant changes in patterns of healthcare use were
      found for acute care, non-acute care or days lost to disability. Multiple
      regression models found higher levels of depression (P = 0.001) to be associated
      with a greater number of non-acute healthcare visits, and found longer duration
      of diabetes (P = 0.019) and lower levels of diastolic blood pressure (P = 0.025)
      to be associated with fewer days lost to disability. CONCLUSIONS: Participation
      in a long-term diabetes self-management education and support intervention had no
      impact on healthcare use in our sample of African-American subjects.

PMID- 24303851
TI  - Strong correlations between circulating chemerin levels and lipoprotein
      subfractions in nondiabetic obese and nonobese subjects.
AB  - OBJECTIVE: Chemerin is a recently described adipokine expressed primarily in the
      white adipose tissue. Compared with lean subjects, circulating chemerin levels
      are significantly elevated in obese individuals and correlate positively with the
      prevalence of various cardiovascular risk factors including altered lipoprotein
      levels. To date, the impact of chemerin on lipoprotein subfractions and its role
      in atherosclerotic processes are still unclear. PATIENTS AND METHODS: Fifty
      nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender
      were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein
      (LDL) and high-density lipoprotein (HDL) subfractions were detected by
      nongradient polyacrylamide gel electrophoresis (Lipoprint). RESULTS: We detected
      significantly higher serum chemerin levels in NDO patients compared with healthy
      controls (590.1 +/- 190.3 ng/ml vs 405 +/- 127.1 ng/ml, P < 0.001). A significant
      positive correlation was found between chemerin and LDL cholesterol levels, while
      chemerin showed a significant negative correlation with the level of HDL
      cholesterol. Significant positive correlation was detected between chemerin and
      the ratio of small dense LDL, while chemerin correlated negatively with the mean
      LDL size. Also, a significant negative correlation was found between serum
      chemerin and the ratio of large HDL subfraction, while there were significant
      positive correlations between chemerin levels and intermediate and small HDL
      subfraction ratios, respectively. CONCLUSION: Chemerin may be involved in the
      regulation of lipoprotein metabolism in obese patients who do not show apparent
      abnormalities of glucose metabolism. Early changes in the distribution of the
      lipoprotein subfractions may contribute to the progression of atherosclerosis,
      leading to increased cardiovascular risk.

PMID- 24303852
TI  - Do part-whole relations produce facilitation in the picture-word interference
      task?
AB  - Three experiments used the picture-word interference task to evaluate competing
      models of lexical access in spoken word production. Both the presence of a part
      whole relation and association between the target and the interfering word were
      manipulated. Part terms associated with targets produced facilitation at early
      stimulus onset asynchronies (SOAs; -300 ms in Experiment 1, -300 and -150 ms in
      Experiment 3), but not at SOA 0 ms. Otherwise, part terms tended to produce
      interference, with unassociated part terms producing a significant semantic
      interference effect (SIE) at SOA of 0 ms in Experiment 1, and a similar trend in
      Experiment 3. Experiment 2 replicated the materials and procedure of Costa,
      Alario, and Caramazza ( 2005 , Experiment 2. On the categorical nature of the
      semantic interference effect in the picture-word interference paradigm.
      Psychonomic Bulletin & Review, 12(1), 125-131), yet failed to find any semantic
      facilitation at SOA 0 ms. We propose that these findings are consistent with
      lexical competition accounts of SIE but difficult to explain in terms of the
      plausibility of the interfering words as responses to the target.

PMID- 24303853
TI  - Explaining mutualism variation: a new evolutionary paradox?
AB  - The paradox of mutualism is typically framed as the persistence of interspecific
      cooperation, despite the potential advantages of cheating. Thus, mutualism
      research has tended to focus on stabilizing mechanisms that prevent the invasion
      of low-quality partners. These mechanisms alone cannot explain the persistence of
      variation for partner quality observed in nature, leaving a large gap in our
      understanding of how mutualisms evolve. Studying partner quality variation is
      necessary for applying genetically explicit models to predict evolution in
      natural populations, a necessary step for understanding the origins of mutualisms
      as well as their ongoing dynamics. An evolutionary genetic approach, which is
      focused on naturally occurring mutualist variation, can potentially synthesize
      the currently disconnected fields of mutualism evolution and coevolutionary
      genetics. We outline explanations for the maintenance of genetic variation for
      mutualism and suggest approaches necessary to address them. 

PMID- 24303854
TI  - Anaesthesia for the Elderly. Foreword.

PMID- 24303855
TI  - The ageing patient--sans everything?

PMID- 24303856
TI  - The impact of pre-operative comprehensive geriatric assessment on postoperative
      outcomes in older patients undergoing scheduled surgery: a systematic review.
AB  - Comprehensive geriatric assessment is an established clinical approach. It
      reduces mortality and improves the physical wellbeing of older people in the
      community or hospitalised for medical reasons. Pre-operative comprehensive
      geriatric assessment seems a plausible method for reducing adverse postoperative
      outcomes. The objectives of this systematic review and narrative synthesis are to
      describe how pre-operative comprehensive geriatric assessment has been used in
      surgical patients and to examine the impact of comprehensive geriatric assessment
      on postoperative outcomes in older patients undergoing scheduled surgery. We
      searched MEDLINE, EMBASE and Web of Science from 1980 to 2013 (week 26). We
      included five studies: two randomised controlled trials and three before-and
      after intervention quasi-experimental studies. Patient populations, interventions
      and outcome measures varied between studies. Both the randomised trials showed
      benefit on postoperative outcomes, including medical complications. Two of the
      before-and-after studies reported a positive impact on postoperative length of
      stay and other outcomes. The heterogeneity of study methods, populations,
      interventions and outcomes precluded meta-analysis. Based on this narrative
      synthesis, pre-operative comprehensive geriatric assessment is likely to have a
      positive impact on postoperative outcomes in older patients undergoing elective
      surgery, but further definitive research is required. Clinical services providing
      pre-operative comprehensive geriatric assessment for older surgical patients
      should be considered. 

PMID- 24303857
TI  - Pre-operative co-morbidity and postoperative survival in the elderly: beyond one
      lunar orbit.
AB  - Mortality is a good measure of killing, but it is a poor measure of cure,
      palliation or the maintenance of function. Nevertheless, it has remained the
      primary metric of hospital care for 200 years. This article discusses the factors
      that contribute to mortality risk and survival trajectories, as well as the
      increasing recognition that surgery kills for months after the last suture is
      tied. This article discusses how disparate factors can usefully combine to
      generate an 'elderly' group with a monthly mortality in excess of 1% and a median
      life expectancy less than 3.5 years. A downloadable spreadsheet is provided that
      combines risk factors to generate mortality risks and their associated survival
      curves, emphasising the importance of looking beyond one postoperative month.

PMID- 24303858
TI  - Patient frailty: the elephant in the operating room.
AB  - For most surgeons and many anaesthetists, patient frailty is currently the
      'elephant in the (operating) room': it is easy to spot, but is often ignored. In
      this paper, we discuss different approaches to the measurement of frailty and
      review the evidence regarding the effect of frailty on peri-operative outcomes.
      We explore the limitations of 'eyeballing' patients to quantify frailty, and
      consider why the frail older patient, challenged by seemingly minor insults in
      the postoperative period, may suffer falls or delirium. Frailty represents a
      state of increased vulnerability to stressors, and older inpatients are exposed
      to multiple stressors in the peri-operative setting. Quantifying frailty is
      likely to increase the precision of peri-operative risk assessment. The Frailty
      Index derived from Comprehensive Geriatric Assessment is a simple and robust way
      to quantify frailty, but is yet to be systematically investigated in the pre
      operative setting. Furthermore, the optimal care for frail patients and the
      reversibility of frailty with prehabilitation are fertile areas for future
      research. 

PMID- 24303860
TI  - Ethical and legal aspects of anaesthesia for the elderly.
AB  - The elderly have the ethical and legal equivalence of younger adults, yet are
      treated differently by society. Numerous recent reports have exposed poor
      inpatient care resulting in part from institutional ageism, which has moral and
      legal implications for healthcare providers. Morally, there is an argument for
      positive 'exceptionalism' in elderly peri-operative care, pursuing quality
      improvement through use of a dignity agenda. Legally, numerous changes in human
      rights, equality, consent, capacity, and end-of-life laws and professional
      guidance have consistently re-emphasised the need for greater communication
      between doctors, patients, their relatives and carers. This review describes
      current ethical thinking and legal precedent (in England and Wales), and directs
      readers to consider areas in which the law might change in the near future,
      particularly with regard to the end-of-life care of elderly surgical patients. 

PMID- 24303861
TI  - The assessment and management of peri-operative pain in older adults.
AB  - A number of recent reports have highlighted the inadequate provision of pain
      relief for older inpatients. Despite the availability of numerous validated pain
      measures, pain remains poorly assessed in some cases and, particularly, in the
      cognitively impaired. Without proper assessment, patients may receive inadequate
      or inappropriate analgesia, both of which can worsen outcome. Most drugs and
      techniques that are used for analgesia in younger patients are also suitable for
      older patients, although dosages may have to be adjusted to avoid the side
      effects that are consequent upon age-related changes in drug pharmacokinetics and
      pharmacodynamics, co-morbidity, frailty, cognitive impairment and polypharmacy.
      This paper reviews current guidelines and methods of assessing pain in the older
      adult, and describes the use of, and problems with, mild, moderate, strong,
      adjuvant and local anaesthetic drugs in the older population for analgesia,
      advocating multimodal intervention to reduce dose-related side-effects,
      particularly of opioids. 

PMID- 24303859
TI  - Should general anaesthesia be avoided in the elderly?
AB  - Surgery and anaesthesia exert comparatively greater adverse effects on the
      elderly than on the younger brain, manifest by the higher prevalence of
      postoperative delirium and cognitive dysfunction. Postoperative delirium and
      cognitive dysfunction delay rehabilitation, and are associated with increases in
      morbidity and mortality among elderly surgical patients. We review the aetiology
      of postoperative delirium and cognitive dysfunction in the elderly with a
      particular focus on anaesthesia and sedation, discuss methods of diagnosing and
      monitoring postoperative cognitive decline, and describe the treatment strategies
      by which such decline may be prevented. 

PMID- 24303862
TI  - National Research Strategies: what outcomes are important in peri-operative
      elderly care?
AB  - Outcomes are essential measures of healthcare effectiveness and efficiency.
      Traditional measures of outcome, such as mortality and length of stay, are
      important and easy to measure but have significant limitations when evaluating
      the peri-operative care of elderly patients. Alternative measures, including
      clinician-described (e.g. complication rates, functional status, frailty) and
      patient-reported outcome and experience measures, are important to provide a
      comprehensive description of peri-operative outcome in the older patient.
      However, few measurement tools have been developed or validated specifically for
      the elderly surgical patient. This paper describes the outcome measures currently
      in use, explores how they might be used to improve the quality of care provision,
      and indicates priority areas for peri-operative outcomes research in the elderly
      surgical patients. 

PMID- 24303863
TI  - Emergency surgery: the big three--abdominal aortic aneurysm, laparotomy and hip
      fracture.
AB  - National reports recommended that peri-operative care should be improved for
      elderly patients undergoing emergency surgery. Postoperative mortality and
      morbidity rates remain high, and indicate that emergency ruptured aneurysm
      repair, laparotomy and hip fracture fixation are high-risk procedures undertaken
      on elderly patients with limited physiological reserve. National audits have
      reported variations in care quality, data that are increasingly being used to
      drive quality improvement through professional guidance. Given that the number of
      elderly patients presenting for emergency surgery is likely to rise as the
      population ages, this review summarises the evidence on which such guidance is
      based, and provides information about how anaesthetists might participate in
      audit and research aimed at improving local and national outcomes for these most
      vulnerable of patients.

PMID- 24303864
TI  - Peri-operative care of the elderly 2014: Association of Anaesthetists of Great
      Britain and Ireland.
AB  - Increasing numbers of elderly patients are undergoing an increasing variety of
      surgical procedures. There is an age-related decline in physiological reserve,
      which may be compounded by illness, cognitive decline, frailty and polypharmacy.
      Compared with younger surgical patients, the elderly are at relatively higher
      risk of mortality and morbidity after elective and (especially) emergency
      surgery. Multidisciplinary care improves outcomes for elderly surgical patients.
      Protocol-driven integrated pathways guide care effectively, but must be
      individualised to suit each patient. The AAGBI strongly supports an expanded role
      for senior geriatricians in coordinating peri-operative care for the elderly,
      with input from senior anaesthetists (consultants/associate specialists) and
      surgeons. The aims of peri-operative care are to treat elderly patients in a
      timely, dignified manner, and to optimise rehabilitation by avoiding
      postoperative complications. Effective peri-operative care improves the
      likelihood of very elderly surgical patients returning to their same pre-morbid
      place of residence, and maintains the continuity of their community care when in
      hospital. Postoperative delirium is common, but underdiagnosed, in elderly
      surgical patients, and delays rehabilitation. Multimodal intervention strategies
      are recommended for preventing postoperative delirium. Peri-operative pain is
      common, but underappreciated, in elderly surgical patients, particularly if they
      are cognitively impaired. Anaesthetists should administer opioid-sparing
      analgesia where possible, and follow published guidance on the management of pain
      in older people. Elderly patients should be assumed to have the mental capacity
      to make decisions about their treatment. Good communication is essential to this
      process. If they clearly lack that capacity, proxy information should be sought
      to determine what treatment, if any, is in the patient's best interests.
      Anaesthetists must not ration surgical or critical care on the basis of age, but
      must be involved in discussions about the utility of surgery and/or
      resuscitation. The evidence base informing peri-operative care for the elderly
      remains poor. Anaesthetists are strongly encouraged to become involved in
      national audit projects and outcomes research specifically involving elderly
      surgical patients. 

PMID- 24303865
TI  - Epidemiology, radiology and histology of atypical femoral fractures.

PMID- 24303866
TI  - Diminished complement-activating capacity through the classical pathway in sera
      from type 2 diabetes mellitus.
AB  - Complement-activating capacity through the classical pathway in type 2 diabetes
      mellitus (T2DM) was examined in the context of free sialic acid as a potential
      modulator of complement activation. Complement-activating capacity was
      investigated in an incubation study of heat-aggregated IgG (HAG) and sera from 42
      T2DM patients. The study demonstrated diminished in-vitro complement-activating
      capacity through the classical pathway in T2DM. Various doses of N-acetyl
      neuraminic acid (NANA) were incubated with normal serum and HAG. Complement
      activation product levels decreased in a NANA dose-dependent manner.
      Isoelectrofocusing analysis in a mixture of NANA and purified C3 indicated that
      C3 changed pI dose-dependently, resulting in the downregulation of complement
      activation. The serum levels of free sialic acid were determined by fluorometric
      assay in the 42 T2DM sera samples, and were significantly increased in patients
      with diminished complement activation. These data indicate that increased serum
      sialic acid may become a candidate for decreasing complement-activating capacity
      in T2DM. 

PMID- 24303867
TI  - Shame, self-acceptance and disclosure in the lives of gay men living with HIV: an
      interpretative phenomenological analysis approach.
AB  - OBJECTIVE: HIV-related stigma is a major driver of poor prognosis for the
      treatment and reduced spread of HIV. The present article provides a qualitative
      analysis surrounding various themes related to stigma and shame as a result HIV.
      DESIGN: Eight gay men recruited from a community HIV clinic contacted the
      researchers in response to a study involving participation in a structured, eight
      week group intervention for HIV-related stigma. Following this group, three men
      took part in open-ended interviews about their thoughts and experiences. METHODS:
      Interpretative phenomenological analysis was used to examine the participants'
      experiences surrounding shame and stigma related to living with HIV. RESULTS:
      Three superordinate themes were identified: social support and the disclosure of
      serostatus, stigma associated with serosorting and attempts to negotiate a
      spoiled identity. CONCLUSION: In San Francisco, a city with a great deal of
      acceptance surrounding HIV and a large, politically active community of persons
      living with HIV, gay men continue to struggle with disclosure and stigma. This
      stigma may be an unexpected result of a high degree of HIV testing and attempts
      by both HIV-positive and negative gay men to practise serosorting.

PMID- 24303868
TI  - Dermatological findings of vitamin B12 deficiency and resolving time of these
      symptoms.
AB  - AIM: The mucocutaneous changes observed during vitamin B12 deficiency in children
      have been published only as case studies and small case series. In this study, we
      aimed to demonstrate the frequency of mucocutaneous changes (particularly
      hyperpigmentation) seen during vitamin B12 deficiency and resolving time of these
      symptoms with vitamin B12 treatment. MATERIAL AND METHODS: This prospective study
      was conducted at the pediatrics outpatient clinic of Harran and Yuzuncu Yil
      University Faculty of Medicine, among 57 patients, aged between 6 and 24 months,
      who were diagnosed with vitamin B12 deficiency following various examinations and
      tests. A detailed examination was performed in respect to skin and mucosal
      findings. Patients with vitamin B12 deficiency were administered intramuscular
      cyanocobalamin. Prospective examination was continued, and resolving time of
      symptoms after treatment was recorded. RESULTS: The mean age of the patients
      enrolled in the study was found to be 12.75 +/- 4.75. Hyperpigmentation was
      reported in 49 (85.96%) patients enrolled in the study; atrophic glossitis in 40
      (70.17%), brittle and matt hair in 13 (22.80%), skin lesions (particularly diaper
      dermatitis) in eight (15.78%) and cheilosis in four (7.01%) patients. Three
      months after the treatment initiation, hyperpigmentation improved in 87.75%,
      atrophic glossitis in 97.5% and brittle and matt hair in 92.3% of the patients.
      Five patients (8.77%) with continuing pigmentation by the end of sixth months
      were considered as nonresponsive to the treatment. CONCLUSION: Deficiency of
      vitamin B12 should be considered in the differential diagnosis of infants who
      present with skin and mucosal lesions.

PMID- 24303869
TI  - Cholesterol removal from various samples by cholesterol-imprinted monosize
      microsphere-embedded cryogels.
AB  - Cholesterol-imprinted monosize poly(glycidyl methacrylate-N-methacryloyl-(L)
      tyrosine methylester) microspheres were embedded into the poly(hydroxyethyl
      methacrylate) (PHEMA) cryogels and the resulting composite cryogel was used for
      the selective removal of cholesterol. Composite cryogels were characterized by
      swelling tests, multipoint BET apparatus, SEM, FTIR and elemental analysis
      studies. Specific surface area of the PHEMA cryogel was increased from 13 to 72.7
      m(2)/g by embedding of microspheres. Composite cryogels removed 80% of
      cholesterol from homogenized milk. The maximum adsorption capacity was found as
      42.7 mg/g for intestinal mimicking solution. After 20 adsorption-desorption
      cycles, there was no remarkable decrease in the adsorption capacity.

PMID- 24303870
TI  - Differentiation of chicken umbilical cord mesenchymal stem cells into beta-like
      pancreatic islet cells.
AB  - In this study, we explored the possibility of using in vitro differentiation to
      create functional beta-like islet cells from chicken umbilical cord mesenchymal
      stem cells (UCMSCs). Passaged UCMSCs were induced to differentiate into
      pancreatic beta-like islet cells. Differentiated cells were observed through
      dithizone staining, and Pdx1 and insulin expressed in differentiated cells were
      detected with immunofluorescence. Insulin and C-peptide production from
      differentiated cells were analyzed using ELISA and western blotting.
      Differentiated cells were found to not only express Pdx1, insulin, and C-peptide,
      but also to display a glucose-responsive secretion of these hormones. 

PMID- 24303871
TI  - The locus of word frequency effects in skilled spelling-to-dictation.
AB  - In spelling-to-dictation tasks, skilled spellers consistently initiate spelling
      of high-frequency words faster than that of low-frequency words. Tainturier and
      Rapp's model of spelling shows three possible loci for this frequency effect:
      spoken word recognition, orthographic retrieval, and response execution of the
      first letter. Thus far, researchers have attributed the effect solely to
      orthographic retrieval without considering spoken word recognition or response
      execution. To investigate word frequency effects at each of these three loci,
      Experiment 1 involved a delayed spelling-to-dictation task and Experiment 2
      involved a delayed/uncertain task. In Experiment 1, no frequency effect was found
      in the 1200-ms delayed condition, suggesting that response execution is not
      affected by word frequency. In Experiment 2, no frequency effect was found in the
      delayed/uncertain task that reflects the orthographic retrieval, whereas a
      frequency effect was found in the comparison immediate/uncertain task that
      reflects both spoken word recognition and orthographic retrieval. The results of
      this two-part study suggest that frequency effects in spoken word recognition
      play a substantial role in skilled spelling-to-dictation. Discrepancies between
      these findings and previous research, and the limitations of the present study,
      are discussed. 

PMID- 24303872
TI  - N,N-dimethylpiperidinium (mepiquat) Part 2. Formation in roasted coffee and
      barley during thermal processing.
AB  - Previous work in model systems has demonstrated that mepiquat can be formed under
      typical roasting conditions from the amino acid lysine via the Maillard reaction
      and trigonelline, the latter alkaloid serving as a methyl donor. This study shows
      for the first time that mepiquat is formed in low mg kg(-1) amounts during the
      coffee roasting process and consequently can be detected in roast and ground as
      well as soluble coffee up to levels of 1.4 mg kg(-1). Darker roast coffees
      contain relatively higher amounts of mepiquat versus light roasted beans, with an
      excellent correlation of mepiquat formation to roast colour (r(2) = 0.99) in
      robusta beans. A survey of 20 of the major green coffee origins (robusta and
      arabica coffees) showed the absence of mepiquat (<0.005 mg kg(-1)). Preliminary
      studies indicate that mepiquat is not formed during processing (thermal
      treatment) in most of the cereal-based foods such as pizza and ready-to-eat
      cereals, but was detected in barley after roasting (0.64 mg kg(-1)). Mepiquat can
      therefore be considered a process-induced compound formed from natural
      constituents during the roasting process. Even considering a high intake of seven
      cups per day of soluble coffee containing 1.4 mg kg(-1) mepiquat in the coffee
      powder (the highest amount measured in this study), the resulting intake would
      exhaust less than 0.2% of the ADI of mepiquat.

PMID- 24303874
TI  - Pectus excavatum: uncommon electrical abnormalities caused by extrinsic right
      ventricular compression.
AB  - We report a case of pectus excavatum associated with ventricular tachycardia
      provoked by exercise in a 19-year-old man. Although this chest deformity has been
      associated with supraventricular dysrhythmias, documented ventricular tachycardia
      has only been reported once. Our patient's ventricular dysrhythmia was treated by
      surgical correction of his pectus excavatum only, and at 3 years follow-up he has
      had no recurrence of his ventricular tachycardia.

PMID- 24303873
TI  - Differentiation of cancer cell origin and molecular subtype by plasma membrane N
      glycan profiling.
AB  - In clinical settings, biopsies are routinely used to determine cancer type and
      grade based on tumor cell morphology, as determined via histochemical or
      immunohistochemical staining. Unfortunately, in a significant number of cases,
      traditional biopsy results are either inconclusive or do not provide full subtype
      differentiation, possibly leading to inefficient or ineffective treatment.
      Glycomic profiling of the cell membrane offers an alternate route toward cancer
      diagnosis. In this study, isomer-sensitive nano-LC/MS was used to directly obtain
      detailed profiles of the different N-glycan structures present on cancer cell
      membranes. Membrane N-glycans were extracted from cells representing various
      subtypes of breast, lung, cervical, ovarian, and lymphatic cancer. Chip-based
      porous graphitized carbon nano-LC/MS was used to separate, identify, and quantify
      the native N-glycans. Structure-sensitive N-glycan profiling identified hundreds
      of glycan peaks per cell line, including multiple isomers for most compositions.
      Hierarchical clusterings based on Pearson correlation coefficients were used to
      quickly compare and separate each cell line according to originating organ and
      disease subtype. Based simply on the relative abundances of broad glycan classes
      (e.g., high mannose, complex/hybrid fucosylated, complex/hybrid sialylated,
      etc.), most cell lines were readily differentiated. More closely related cell
      lines were differentiated based on several-fold differences in the abundances of
      individual glycans. Based on characteristic N-glycan profiles, primary cancer
      origins and molecular subtypes could be distinguished. These results demonstrate
      that stark differences in cancer cell membrane glycosylation can be exploited to
      create an MS-based biopsy, with potential applications toward cancer diagnosis
      and direction of treatment. 

PMID- 24303875
TI  - Effect of monochromatic excimer light on palmoplantar pustulosis: a clinical
      study performed in a private clinic by a dermatological specialist.
AB  - Palmoplantar pustulosis (PPP) is currently treated with various modalities,
      including excimer light, a form of ultraviolet lamp. This study reports effect of
      excimer light treatment in 34 Japanese PPP patients treated at a private clinic
      by one doctor, who was certified as a dermatological specialist by the Japanese
      Dermatological Association. The statistical analyses were performed upon a
      collaborative basis with faculties in universities. Disease response scores were
      determined by response to excimer light treatment. Scores of 1, 2, 3 or 4 were
      assigned to patients whose palmoplantar pustular psoriasis area and severity
      index (PPPASI) decreased to 25% or less, 25.1-50%, 50.1-75% or more than 75.1% of
      pretreatment PPPASI, respectively. In this study, 44.1% PPP cases had scores of 1
      or 2, and considered good responders to excimer light treatment. There were no
      statistical differences between males and females, and between older (>=40 years)
      and younger groups (<=39 years) in terms of disease response score. Disease
      duration did not show any significant difference among these scores. Treatment
      times, total amount of ultraviolet and total treatment duration showed
      significant differences between score 1 and score 4 groups (P = 0.0164, =0.0137
      and =0.0267, respectively). Particular interest was paid to smoking habits.
      Smoking in male patients was significantly higher than that in female patients (P
      = 0.0169). There was no statistical difference between smokers and non-smokers in
      terms of response to excimer light. In conclusion, this study suggested that
      excimer light is useful for both initial regimen and suppression of exacerbation
      in treatments of PPP. 

PMID- 24303876
TI  - Electrical modulation of fano resonance in plasmonic nanostructures using
      graphene.
AB  - Pauli blocking of interband transistions gives rise to tunable optical properties
      in single layer graphene (SLG). This effect is exploited in a graphene
      nanoantenna hybrid device where Fano resonant plasmonic nanostructures are
      fabricated on top of a graphene sheet. The use of Fano resonant elements enhances
      the interaction of incident radiation with the graphene sheet and enables
      efficient electrical modulation of the plasmonic resonance. We observe
      electrically controlled damping in the Fano resonances occurring at approximately
      2 MUm, and the results are verified by full-wave 3D finite-element simulations.
      Our approach can be used for development of next generation of tunable plasmonic
      and hybrid nanophotonic devices. 

PMID- 24303877
TI  - Towards standardization of UV eye protection: what can be learned from
      photodermatology?
AB  - While knowledge about standardization of skin protection against ultraviolet
      radiation (UVR) has progressed over the past few decades, there is no uniform and
      generally accepted standardized measurement for UV eye protection. The literature
      provides solid evidence that UV can induce considerable damage to structures of
      the eye. As well as damaging the eyelids and periorbital skin, chronic UV
      exposure may also affect the conjunctiva and lens. Clinically, this damage can
      manifest as skin cancer and premature skin ageing as well as the development of
      pterygia and premature cortical cataracts. Modern eye protection, used daily,
      offers the opportunity to prevent these adverse sequelae of lifelong UV exposure.
      A standardized, reliable and comprehensive label for consumers and professionals
      is currently lacking. In this review we (i) summarize the existing literature
      about UV radiation-induced damage to the eye and surrounding skin; (ii) review
      the recent technological advances in UV protection by means of lenses; (iii)
      review the definition of the Eye-Sun Protection Factor (E-SPF(r)), which
      describes the intrinsic UV protection properties of lenses and lens coating
      materials based on their capacity to absorb or reflect UV radiation; and (iv)
      propose a strategy for establishing the biological relevance of the E-SPF.

PMID- 24303878
TI  - The role of cyclodextrins in ORAC-fluorescence assays. antioxidant capacity of
      tyrosol and caffeic acid with hydroxypropyl-beta-cyclodextrin.
AB  - Tyrosol and caffeic acid are biophenols that contribute to the beneficial
      properties of virgin olive oil. The influence of hydroxypropyl-beta-cyclodextrin
      (HPbeta-CD) on their respective antioxidant capacities was analyzed. The ORAC
      antioxidant activity of tyrosol (expressed as MUM Trolox equivalents/MUM Tyrosol)
      was 0.83 +/- 0.03 and it increased up to 1.20 +/- 0.11 in the presence of 0.8 mM
      HPbeta-CD. However, the ORAC antioxidant activity of caffeic acid experienced no
      change. The different effect of HPbeta-CD on each compound was discussed. In
      addition, the effect of increasing concentrations of different cyclodextrins in
      the development of ORAC-fluorescence (ORAC-FL) assays was studied. The ORAC
      signal was higher for HPbeta-CD, followed by Mbeta-CD, beta-CD, gamma-CD and
      finally alpha-CD. These results could be explained by the formation of inclusion
      complexes with fluorescein. 

PMID- 24303879
TI  - Insurer market structure and variation in commercial health care spending.
AB  - OBJECTIVE: To examine the relationship between insurance market structure and
      health care prices, utilization, and spending. DATA SOURCES: Claims for 37.6
      million privately insured employees and their dependents from the Truven Health
      Market Scan Database in 2009. Measures of insurer market structure derived from
      Health Leaders Inter study data. METHODS: Regression models are used to estimate
      the association between insurance market concentration and health care spending,
      utilization, and price, adjusting for differences in patient characteristics and
      other market-level traits. RESULTS: Insurance market concentration is inversely
      related to prices and spending, but positively related to utilization. Our
      results imply that, after adjusting for input price differences, a market with
      two equal size insurers is associated with 3.9 percent lower medical care
      spending per capita (p = .002) and 5.0 percent lower prices for health care
      services relative to one with three equal size insurers (p < .001). CONCLUSION:
      Greater fragmentation in the insurance market might lead to higher prices and
      higher spending for care, suggesting some of the gains from insurer competition
      may be absorbed by higher prices for health care. Greater attention to prices and
      utilization in the provider market may need to accompany procompetitive insurance
      market strategies.

PMID- 24303880
TI  - Isoniazid-induced liver injury and immune response in mice.
AB  - Isoniazid (INH) is associated with one of the highest incidences of idiosyncratic
      drug-induced liver failure of any commonly prescribed drug. The mechanism of this
      liver injury remains uncertain, and a valid animal model would greatly facilitate
      mechanistic studies. Most studies of INH-induced liver toxicity have been acute
      studies performed in rats with high doses of the drug, and this is very different
      from the idiosyncratic liver injury that occurs in humans. It has previously been
      demonstrated that covalent binding of INH in the liver of mice is greater than in
      rats and more like that in humans. Therefore, mice should be a better species in
      which to develop an animal model of INH-induced liver injury. Treatment of Cbl-b(
      /-) and PD1(-/-) mice, which have impaired immune tolerance, resulted in greater
      injury than their C57BL/6 background, but not liver failure. This suggested that
      the injury was mediated by the adaptive immune system; however, Rag(-/-) mice,
      which do not have competent T- and B-cells, sustained more liver injury than
      C57BL/6 wild-type mice. This suggested that the adaptive immune system also
      played a protective role. INH treatment also led to a decrease in the
      inflammatory cytokines IL-1alpha and IL-12, which suggests that the drug may have
      immunosuppressive properties. In short, a mouse model was developed of INH
      induced liver injury in which the immune system appears to play a both protective
      and pathogenic role, but this study was unable to develop a model of INH-induced
      liver failure.

PMID- 24303881
TI  - Association of quantitative assessment of the intrafollicular proliferation index
      with outcome in follicular lymphoma.
AB  - The role of the proliferation index (PI) as an outcome predictor in follicular
      lymphoma (FL) isn't clear. We have previously demonstrated that quantitative
      image analysis (QIA) is a robust tool for PI determination and the present study
      aimed to determine the significance of the PI for outcome in low-grade FL. One
      hundred and twenty-nine patients with grade 1-2 FL were retrospectively analysed.
      Slides were scanned digitally and follicle/tumour-involved areas were annotated.
      The intrafollicular PI was estimated by analysing a median of 10 follicles per
      case. Patients were divided into two groups: PI < 30%, PI >= 30% and clinical
      outcome was analysed. Among the 129 patients analysed, intrafollicular PI ranged
      from 0.6 to 63.2% with a median of 23.3%. Overall survival was not influenced by
      PI group. Among those patients initially observed, intrafollicular PI < 30% was
      associated with longer time to first therapy compared to patients with a PI >=
      30%. In the group of patients that were treated at diagnosis, PI was not
      predictive of time to treatment failure (TTTF). Intrafollicular PI is an
      important predicator of TTFT for patients who are candidates for observation.
      Further confirmation in an independent cohort of patients is necessary to
      determine the clinical validity of the results. 

PMID- 24303882
TI  - Experimental exposure of adult San Marcos salamanders and larval leopard frogs to
      the cercariae of Centrocestus formosanus.
AB  - The gill parasite Centrocestus formosanus (Trematoda: Heterophyidae) is an exotic
      parasite of concern in Texas because it has been shown to infect multiple
      threatened and endangered fish species. The purpose of this study was to
      determine if C. formosanus could present a threat to larval anurans, as well as
      threatened neotenic salamanders endemic to the spring-fed systems of Texas. We
      exposed adults of the San Marcos salamander Eurycea nana (Caudata:
      Plethodontidae) and tadpoles of the Rio Grande leopard frog Lithobates
      berlandieri (Anura: Ranidae) to the cercariae of C. formosanus . The San Marcos
      salamander showed no signs of metacercarial infection, suggesting that E. nana
      may be refractory to C. formosanus cercariae. Centrocestus formosanus readily
      infects the gills of leopard frog tadpoles, but the metacercariae apparently died
      prior to reaching maturity in our tadpoles.

PMID- 24303883
TI  - Pregnancy outcome after ICSI with thawed testicular sperm from men with non
      obstructive azoospermia compared to ICSI with ejaculated sperm from men with
      severe oligoasthenoteratozoospermia and IVF with normal ejaculated sperm.
AB  - The aim of the study was to evaluate the clinical pregnancy outcomes, fetal
      complications and malformation rate of intracytoplasmic injection of thawed
      cryopreseverd sperm extracted by testicular aspiration from men with non
      obstructive azoospermia (NOA) compared with intracytoplasmic injection of fresh
      ejaculated sperm from men with severe oligoteratoasthenozoospermia (OTA) and
      standard in vitro fertilization using ejaculated sperm from normospermic men. The
      mean oocyte fertilization rate was significantly lowest for ICSI with testicular
      aspirated sperm (NOA group). However, there was no significant difference among
      the three groups in pregnancy outcomes, namely rates of spontaneous abortion,
      biochemical pregnancy, extrauterine pregnancy, singleton multifetal pregnancy,
      preterm delivery before 36 weeks' gestation, maternal complications, transfer to
      the neonatal intensive care unit, intrauterine growth restriction or fetal
      malformations. These results suggest that despite some earlier findings that
      intracytoplasmic injection of aspirated sperm from men with NOA is associated
      with lower fertilization rates and embryo quality, the pregnancy and immediate
      neonatal outcomes may be unaffected.

PMID- 24303884
TI  - Anti-Mullerian hormone levels in women with polycystic ovarian syndrome compared
      with normal women of reproductive age in China.
AB  - OBJECTIVES: Aim was to evaluate anti-Mullerian-hormone (AMH) in women with
      polycystic ovary syndrome (PCOS) comparing with normo-ovulatory women, and to
      assess for the first time AMH levels across reproductive lifespan in Chinese
      women. METHODS: Within the prospective cross-sectional study in PCOS cases and in
      normal subjects, AMH and other hormone levels were measured in early follicular
      phase in five age groups. Additionally ovarian ultrasound parameters were
      assessed. RESULTS: A total of 437 PCOS patients and 150 normo-ovulatory women
      matched by age were included. AMH levels were 2- to 3-fold higher in PCOS cases.
      In both groups AMH decreased with age in a non-linear pattern. In normo-ovulatory
      women AMH levels were relatively constant from 18 to 25 years and then declined
      with age. In contrast, AMH in PCOS cases declined with an increasing rate from 18
      to 45 years, narrowing the difference in older women. CONCLUSIONS: AMH may be a
      useful parameter to assess the severity and prognosis of PCOS since certain
      differences exist to normo-ovulatory women. Further studies may improve the
      understanding of the relationship between AMH levels and age, providing more
      scientific basis for fertility counselling for both healthy women and PCOS cases.

PMID- 24303885
TI  - The role of VEGF and its receptors in the etiology of early pregnancy loss.
AB  - OBJECTIVE: This study aimed to investigate the role of vascular endothelial
      growth factor (VEGF) and its receptors (VEGFR1, VEGFR2) in maternal and embryonic
      tissues in the etiology of early pregnancy loss. METHODS: Immunohistochemistry
      was used to analyze the expression of VEGF and its receptors in placental and
      decidual tissues of 80 women with spontaneous incomplete abortion (n = 20),
      missed abortion (n = 20), blighted ovum (n = 20) and from early terminated
      pregnancies (n = 20). RESULTS: Compared with the controls, all study groups
      showed weaker VEGF immunoreactivity in cytotrophoblasts and syncytiotrophoblasts
      of placental villi and endothelial cells of decidua (p = 0.002, p = 0.003, p <
      0.001 respectively). Decidual endothelial cells of study groups except for
      blighted ovum showed weaker VEGFR1 immunoreactivity as compared to controls (p <
      0.001). Placental villi cytotrophoblasts, syncytiotrophoblasts, decidual
      endothelial cells and endometrial gland epithelial cells showed weaker VEGFR2
      immunoreactivity in all study groups compared to controls (p < 0.001). Placental
      villi endothelial cells showed the weakest VEGFR2 immunoreactivity in incomplete
      abortion group and the strongest staining in the blighted ovum group (p < 0.001).
      CONCLUSION: These results suggest that decreased expression of VEGFR1 in decidua
      and weaker VEGF and VEGFR2 expression in placental villi and decidua may be
      associated with early pregnancy loss.

PMID- 24303886
TI  - Reference values in ovarian response to controlled ovarian stimulation throughout
      the reproductive period.
AB  - Abstract The age-related decline in ovarian response to gonadotropins has been
      well known since the beginning of ovarian stimulation in IVF cycles and has been
      considered secondary to the age-related decline in ovarian reserve. The objective
      of this study was to establish reference values and to construct nomograms of
      ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We
      analyzed our database containing information on IVF cycles. According to
      inclusion and exclusion criteria, a total of 703 patients were selected. Among
      inclusion criteria, there were regular menstrual cycle, treatment with a long
      GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at
      least 200 IU per day. To estimate the reference values of ovarian response, the
      CG-LMS method was used. A linear decline in the parameters of ovarian response
      with age was observed: the median number of oocytes decreases approximately by
      one every three years, and the median number of follicles >16 mm by one every
      eight years. The number of oocytes and growing follicles corresponding to the
      5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed
      the well known negative relationship between ovarian response to FSH and female
      ageing and permitted the construction of nomograms of ovarian response. 

PMID- 24303887
TI  - Major groove binding track residues of the connection subdomain of human
      immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at
      high temperatures.
AB  - At high temperatures, RNA denaturation can improve the efficiency and specificity
      of reverse transcription. Refined structures and molecular models of HIV-1
      reverse transcriptases (RTs) from phylogenetically distant clades (i.e., group M
      subtype B and group O) revealed a major interaction between the template-primer
      and the Arg358-Gly359-Ala360 triad in the large subunit of HIV-1M/B RT. However,
      fewer contacts were predicted for the equivalent Lys358-Ala359-Ser360 triad of
      HIV-1O RT and the nucleic acid. An engineered HIV-1O K358R/A359G/S360A RT showed
      increased cDNA synthesis efficiency above 68  degrees C, as determined by
      qualitative and quantitative reverse transcription polymerase chain reactions. In
      comparison with wild-type HIV-1O RT, the mutant enzyme showed higher thermal
      stability but retained wild-type RNase H activity. Mutations that increased the
      accuracy of HIV-1M/B RTs were tested in combination with the K358R/A359G/S360A
      triple mutation. Some of them (e.g., F61A, K65R, K65R/V75I, and V148I) had a
      negative effect on reverse transcription efficiency above 65  degrees C. RTs with
      improved DNA binding affinities also showed higher cDNA synthesis efficiencies at
      elevated temperatures. Two of the most thermostable RTs (i.e., mutants
      T69SSG/K358R/A359G/S360A and K358R/A359G/S360A/E478Q) showed moderately increased
      fidelity in forward mutation assays. Our results demonstrate that the triad of
      Arg358, Gly359, and Ala360 in the major groove binding track of HIV-1 RT is a
      major target for RT stabilization, and most relevant for improving reverse
      transcription efficiency at high temperatures.

PMID- 24303888
TI  - Argument disrupts interpersonal synchrony.
AB  - Research on interpersonal convergence and synchrony characterizes the way in
      which interacting individuals come to have more similar affect, behaviour, and
      cognition over time. Although its dynamics have been explored in many settings,
      convergence during conflict has been almost entirely overlooked. We present a
      simple but ecologically valid study comparing how different situational contexts
      that highlight affiliation and argument impact interpersonal convergence of body
      movement and to what degree emotional states affect convergence in both
      conversational settings. Using linear mixed-effect models, we found that in-phase
      bodily synchrony decreases significantly during argument. However, affective
      changes did not significantly predict changes in levels of interpersonal
      synchrony, suggesting that differences in affect valences between affiliation and
      argument cannot solely explain our results. 

PMID- 24303889
TI  - Commentary on: "American Thyroid Association Guide to investigating thyroid
      hormone economy and action in rodent and cell models," Bianco et al.

PMID- 24303890
TI  - Elucidation of carbene ambiphilicity leading to the discovery of reversible
      ammonia activation.
AB  - An N,N'-diamidocarbene (DAC) was found to activate a broad range of primary as
      well as secondary aliphatic and aromatic amines. The relative rates measured for
      the insertion of the DAC into the primary amines were consistent with an
      electrophilic activation mechanism; in contrast, the DAC functioned as a
      nucleophile upon treatment with secondary aryl amines. Collectively, these
      results constituted the first ambiphilic process for an isolable carbene. By
      comparison, an analogous diaminocarbene was found to serve exclusively as a
      nucleophile under similar conditions and led to the discovery of the first
      organic reagent to reversibly activate ammonia. 

PMID- 24303891
TI  - Spit and venom from scytodes spiders: a diverse and distinct cocktail.
AB  - Spiders from the family Scytodidae have a unique prey capturing technique: they
      spit a zig-zagged silken glue to tether prey to a surface. Effectiveness of this
      sticky mixture is based on a combination of contraction and adhesion, trapping
      prey until the spider immobilizes it by envenomation and then feeds. We identify
      components expressed in Scytodes thoracica venom glands using combined
      transcriptomic and proteomic analyses. These include homologues of toxic proteins
      astacin metalloproteases and potentially toxic proteins including venom allergen,
      longistatin, and translationally controlled tumor protein (TCTP). We classify 19
      distinct groups of candidate peptide toxins; 13 of these were detected in the
      venom, making up 35% of the proteome. Six have significant similarity to toxins
      from spider species spanning mygalomorph and nonhaplogyne araneomorph lineages,
      suggesting their expression in venom is phylogenetically widespread. Twelve
      peptide toxin groups have homologues in venom gland transcriptomes of other
      haplogynes. Of the transcripts, approximately 50% encode glycine-rich peptides
      that may contribute to sticky fibers in Scytodes spit. Fifty-one percent of the
      identified venom proteome is a family of proteins that is homologous to sequences
      from Drosophila sp. and Latrodectus hesperus with uncharacterized function.
      Characterization of these components holds promise for discovering new functional
      activity. 

PMID- 24303892
TI  - Identification of quantitative trait loci affecting gastrointestinal parasite
      resistance in an experimental Angus population.
AB  - DNA markers associated with quantitative trait loci (QTL) affecting host
      tolerance to gastrointestinal (GI) parasite infection are ideal targets for
      marker-assisted selection. However, few studies in cattle have attempted to
      identify this type of QTL due to the difficulty of generating accurate phenotypic
      data from a resource population with adequate statistical power for detection.
      For this effort, we amassed fecal egg count (FEC) measures from annual natural
      field challenges with GI nematodes that spanned 12 different contemporary groups
      of Angus calves (1992-2000) derived from a closed breeding population. FEC and
      blood pepsinogen measures were taken weekly over a 26-week period post-weaning,
      and the FEC data were Box-Cox transformed to normalize the distribution of
      phenotypes. These 305 test animals and more than 100 founding animals from the
      extended pedigree were genotyped across 190 microsatellites markers. The genome
      wide analyses identified a suggestive genome-wide QTL on bovine chromosome (Chr)
      8 (P < 0.002) and nominal QTL on Chr 4, 12 and 17 (P < 0.05). These findings were
      unique for cattle, and some corresponded to previously identified QTL locations
      for parasite-related traits in sheep to provide genome locations for further fine
      mapping of parasite resistance/susceptibility in Angus cattle. 

PMID- 24303893
TI  - Twiddler syndrome.

PMID- 24303894
TI  - Gold nanorod-assembled PEGylated graphene-oxide nanocomposites for photothermal
      cancer therapy.
AB  - Gold nanorod-attached PEGylated graphene-oxide (AuNR-PEG-GO) nanocomposites were
      tested for a photothermal platform both in vitro and in vivo. Cytotoxicity of
      AuNR was reduced after encapsulation with PEG-GO along with the removal of
      cetyltrimethylammonium bromide (CTAB) from AuNR by HCl treatment. Cellular
      internalization of the CTAB-eliminated AuNR-PEG-GO nanocomposites was examined
      using dark-field microscopy (DFM), confocal Raman microscopy and transmission
      electron microscopy (TEM). To determine the photothermal effect of the AuNR-PEG
      GO nanocomposites, A431 epidermoid carcinoma cells were irradiated with Xe-lamp
      light (60 W cm(-2)) for 5 min after treatment with the AuNR-PEG-GO nanocomposites
      for 24 h. Cell viability significantly decreased by ~40% when the AuNR-PEG-GO
      encapsulated nanocomposites were irradiated with light as compared with the cells
      treated with only the AuNR-PEG-GO nanocomposites without any illumination. In
      vivo tumor experiments also indicated that HCl-treated AuNR-PEG-GO nanocomposites
      might efficiently reduce tumor volumes via photothermal processes. Our graphene
      and AuNR nanocomposites will be useful for an effective photothermal therapy.

PMID- 24303895
TI  - Selective excitation of single molecules coupled to the bright mode of a
      plasmonic cavity.
AB  - Plasmon-based optical antennas featuring a nanometer-sized gap can enhance the
      photophysical properties of solid-state quantum emitters by several orders of
      magnitude at room temperature. However, controlling the position and orientation
      of an isolated emitter in a metallic resonator, at the nanometer scale, has only
      been achieved in scanning probe geometries. Using radially polarized cylindrical
      vector beams and DNA-assembled gold nanoparticle dimers, we demonstrate the
      reproducible interaction of single dye molecules with the bright longitudinal
      mode of a plasmonic cavity, achieving decay rate enhancements of 2 orders of
      magnitude. These results demonstrate that interfacing efficiently isolated
      quantum emitters and optical nanoantennas is possible on a large scale. 

PMID- 24303896
TI  - The influence of the periodontal biotype on peri-implant tissues around immediate
      implants with and without xenografts. Clinical and micro-computerized tomographic
      study in small Beagle dogs.
AB  - OBJECTIVE: Soft tissues and buccal bone plate remodeling after immediate
      implantation in sockets with thin buccal bone, using the flapless approach with
      or without bone graft into the buccal gap, was compared between sites with thin
      and normal gingiva. MATERIAL AND METHODS: Eight dogs had the gingiva of one side
      of the mandible thinned, the mandibular premolars were extracted without flaps,
      and 4 implants were installed in each side, positioned 1.5 mm from the buccal
      bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG +
      GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM
      (CG with grafting material). Buccal bone thickness (BBT), thickness of
      keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and
      probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were
      sacrificed and the samples were analyzed by micro-computerized tomography.
      RESULTS: A thin BBT was observed in all the dogs. The presurgical procedures
      reduced TKT in the test group, with minimal changes of the AT. There were no
      statistically significant differences among the groups for the clinical
      parameters and the tomographic analysis showed similar linear and tri-dimensional
      bone reduction in all the groups. CONCLUSION: The thickness of the buccal bone
      was a fundamental factor in buccal bone plate resorption, even with flapless
      implantation. The decrease in gingival thickness or the addition of a biomaterial
      in the gap did not influence the results.

PMID- 24303897
TI  - Subsets of human natural killer cells and their regulatory effects.
AB  - Human natural killer (NK) cells have distinct functions as NK(tolerant) ,
      NK(cytotoxic) and NK(regulatory) cells and can be divided into different subsets
      based on the relative expression of the surface markers CD27 and CD11b. CD27+ NK
      cells, which are abundant cytokine producers, are numerically in the minority in
      human peripheral blood but constitute the large population of NK cells in cord
      blood, spleen, tonsil and decidua tissues. Recent data suggest that these NK
      cells may have immunoregulatory properties under certain conditions. In this
      review, we will focus on these new NK cell subsets and discuss how regulatory NK
      cells may serve as rheostats or sentinels in controlling inflammation and
      maintaining immune homeostasis in various organs.

PMID- 24303898
TI  - Treatment for cutaneous arteritis patients with mononeuritis multiplex and
      elevated C-reactive protein.
AB  - Cutaneous arteritis (cutaneous polyarteritis nodosa, CA) is a necrotizing
      vasculitis of arteries within the skin. CA is a new classification under single
      organ vasculitis, as adopted by the 2012 Chapel Hill consensus conference (CHCC
      2012). Some patients originally diagnosed as having CA could develop additional
      disease manifestations that warrant reclassifying as systemic polyarteritis
      nodosa (PAN) according to the CHCC 2012. We retrospectively investigated 101
      patients with CA seen at our department between 2003 and 2012. There was a
      significantly higher frequency of inflammatory plaques and leg edema in CA
      patients with elevated C-reactive protein (CRP) compared to CA patients with
      normal CRP. Similarly, there were significant differences in the incidence of
      arthralgia and mononeuritis multiplex between the two patient groups. We found
      significantly positive correlations between CRP and creatinine titers in serum in
      all 101 CA patients. Prednisolone was administrated in a significantly greater
      percentage of patients with elevated CRP compared to patients with normal CRP.
      Repeated i.v. cyclophosphamide pulse therapy (IV-CY) with prednisolone therapy at
      an early stage resulted in complete resolution without adverse effects or severe
      complications. We regard inflammatory plaques and leg edema with elevated serum
      CRP as an indication of a more severe condition, and treated them effectively
      with prednisolone. Assuming mononeuritis multiplex and/or arthritis exist with
      elevated CRP, we propose that earlier treatment by IV-CY with prednisolone should
      be indicated for CA patients who demonstrate these more severe manifestations to
      prevent progression to PAN. 

PMID- 24303900
TI  - The oxidative capacity of indoor atmospheres.

PMID- 24303899
TI  - The multifunctional role of the pallilysin-associated Treponema pallidum protein,
      Tp0750, in promoting fibrinolysis and extracellular matrix component degradation.
AB  - The mechanisms that facilitate dissemination of the highly invasive spirochaete,
      Treponema pallidum, are incompletely understood. Previous studies showed the
      treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation
      capability, suggesting a role in treponemal dissemination. In the current study
      we report characterization of the functionally linked protein Tp0750. Structural
      modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain,
      a protein-protein interaction domain commonly observed in extracellular matrix
      (ECM)-binding proteins. We report Tp0750 is a serine protease that degrades the
      major clot components fibrinogen and fibronectin. We also demonstrate Tp0750
      cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by
      several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we
      show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a
      specific and dose-dependent manner. These results suggest Tp0750 constitutes a
      multifunctional protein that is able to (1) degrade infection-limiting clots by
      both inhibiting clot formation through degradation of host coagulation cascade
      proteins and promoting clot dissolution by complexing with host proteins involved
      in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP-like
      proteolysis of host components. We propose that through these activities Tp0750
      functions in concert with pallilysin to enable T. pallidum dissemination. 

PMID- 24303901
TI  - Effect of lyophilized grapefruit juice on P-glycoprotein-mediated drug transport
      in-vitro and in-vivo.
AB  - The administration of grapefruit juice (GFJ) has been postulated to inhibit the
      activity of P-glycoprotein (P-gp) transport system and thus can enhance the
      uptake of substrate drugs. However, for various reasons, the results obtained
      have been always swaying between confirmation and refutation. This study aims at
      re-evaluating the effect of lyophilized freshly-prepared grapefruit juice (LGFJ)
      prepared from the whole peeled fruit on P-gp activity using the model drug
      doxorubicin (DOX) in-vitro and timolol maleate (TM) in-vivo. Human uterine
      sarcoma MES-SA/DX5v cells, grown under nanomolar concentration of DOX and highly
      expressing P-gp, were used as model cells for in-vitro studies whereas white New
      Zealand male rabbits were used for in-vivo studies. Results showed that the
      accumulation of DOX in MES-SA/DX5v cells was increased by 18.3 +/- 2.0% in
      presence of LGFJ compared to control experiments. Results from in-vivo absorption
      studies showed that the relative oral bioavailability of TM ingested with LGFJ
      was significantly higher by 70% and 43% compared to the oral bioavailability of
      TM ingested with saline and a commercial GFJ, respectively. This study as such
      confirms the inhibitory effects of LGFJ on P-gp efflux proteins and highlights
      the superiority of using lyophilized freshly prepared juices over the
      commercially available juices in research studies. Also, the results call for
      further studies to assess the possibility of co-administrating LGFJ with anti
      cancer agents to modulate multidrug resistance in their cellular environment or
      incorporating LGFJ in solid dosage forms to improve oral bioavailability of
      drugs.

PMID- 24303902
TI  - Memory bias for negative emotional words in recognition memory is driven by
      effects of category membership.
AB  - Recognition memory studies often find that emotional items are more likely than
      neutral items to be labelled as studied. Previous work suggests this bias is
      driven by increased memory strength/familiarity for emotional items. We explored
      strength and bias interpretations of this effect with the conjecture that
      emotional stimuli might seem more familiar because they share features with
      studied items from the same category. Categorical effects were manipulated in a
      recognition task by presenting lists with a small, medium or large proportion of
      emotional words. The liberal memory bias for emotional words was only observed
      when a medium or large proportion of categorised words were presented in the
      lists. Similar, though weaker, effects were observed with categorised words that
      were not emotional (animal names). These results suggest that liberal memory bias
      for emotional items may be largely driven by effects of category membership. 

PMID- 24303903
TI  - Existence of solutions of a two-dimensional boundary value problem for a system
      of nonlinear equations arising in growing cell populations.
AB  - In the paper [A. Ben Amar, A. Jeribi, and B. Krichen, Fixed point theorems for
      block operator matrix and an application to a structured problem under boundary
      conditions of Rotenberg's model type, to appear in Math. Slovaca. (2014)], the
      existence of solutions of the two-dimensional boundary value problem (1) and (2)
      was discussed in the product Banach space L(p)*L(p) for p?(1, infinity). Due to
      the lack of compactness on L1 spaces, the analysis did not cover the case p=1.
      The purpose of this work is to extend the results of Ben Amar et al. to the case
      p=1 by establishing new variants of fixed-point theorems for a 2*2 operator
      matrix, involving weakly compact operators.

PMID- 24303904
TI  - Stability and invariant manifolds of a generalized Beddington host-parasitoid
      model.
AB  - We will investigate the stability and invariant manifolds of a new discrete host
      parasitoid model. It is a generalization of the Beddington-Nicholson-Bailey
      model. Our study establishes analytically, for the first time, the stability of
      the coexistence fixed point. 

PMID- 24303905
TI  - Heterogeneity in multiple transmission pathways: modelling the spread of cholera
      and other waterborne disease in networks with a common water source.
AB  - Many factors influencing disease transmission vary throughout and across
      populations. For diseases spread through multiple transmission pathways, sources
      of variation may affect each transmission pathway differently. In this paper we
      consider a disease that can be spread via direct and indirect transmission, such
      as the waterborne disease cholera. Specifically, we consider a system of multiple
      patches with direct transmission occurring entirely within patch and indirect
      transmission via a single shared water source. We investigate the effect of
      heterogeneity in dual transmission pathways on the spread of the disease. We
      first present a 2-patch model for which we examine the effect of variation in
      each pathway separately and propose a measure of heterogeneity that incorporates
      both transmission mechanisms and is predictive of R(0). We also explore how
      heterogeneity affects the final outbreak size and the efficacy of intervention
      measures. We conclude by extending several results to a more general n-patch
      setting.

PMID- 24303906
TI  - A comparison of a deterministic and stochastic model for hepatitis C with an
      isolation stage.
AB  - We formulate a deterministic epidemic model for the spread of Hepatitis C
      containing an acute, chronic and isolation class and analyse the effects of the
      isolation class on the transmission dynamics of the disease. We calculate the
      basic reproduction number R(0) and show that for R(0)<=1, the disease-free
      equilibrium is globally asymptotically stable. In addition, it is shown that for
      a special case when R(0)>1, the endemic equilibrium is locally asymptotically
      stable. Furthermore, an analogous stochastic epidemic model for Hepatitis C is
      formulated using a continuous time Markov chain. Numerical simulations are used
      to estimate the mean, variance and probability distributions of the discrete
      random variables and these are compared to the steady-state solutions of the
      deterministic model. Finally, the expected time to disease extinction is
      estimated for the stochastic model and the impact of isolation on the time to
      extinction is explored.

PMID- 24303907
TI  - A generalized two-sex logistic model.
AB  - We provide a generalization of the logistic two-sex model with ephemeral pair
      bonds and with stable couples without assuming any specific mathematical form for
      fertility, mortality and the mating function. In particular, we establish a
      necessary and sufficient condition on the fertility/mortality density-dependent
      ratio that ensures the existence of the logistic behaviour. Several differences
      and similarities between the two models are also provided. 

PMID- 24303908
TI  - The effect of intercalated degrees on student involvement in academic medicine.

PMID- 24303909
TI  - Adult lymphoblastic leukaemia presenting with nephromegaly.

PMID- 24303910
TI  - Simultaneous type-I/type-II emission from CdSe/CdS/ZnSe nano-heterostructures.
AB  - Core/intermediate/shell (C/I/S) structures with Type-I emission are well-known
      and are gaining immense importance due to their superior luminescence properties.
      Here, we report a unique C/I/S structure composed of CdSe/CdS/ZnSe that exhibits
      both Type-I and Type-II phenomena. The structures have been well characterized
      using a combination of optical and structural techniques. The photoluminescence
      (PL) and photoluminescence excitation (PLE) data indicate the formation of a
      combined Type-I and Type-II structure in one material, results supported by
      simple theoretical calculations. Single particle fluorescence reveals
      colocalization of both the emissions. The X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) results confirm the structure of these
      particles. The time-resolved fluorescence studies show the possibility of tuning
      the lifetime of these materials by changing the Type-I/Type-II thickness ratios.
      It is possible to form these two separate excitons in the same system separated
      by a CdS intermediate layer that acts both as a barrier and an active member of
      the Type-II system allowing the generation and recombination of two excitons, in
      violation of Kasha's rule. 

PMID- 24303912
TI  - An outbreak of CTX-M-15 -producing Escherichia coli, Enterobacter cloacae, and
      Klebsiella in a children's hospital in Finland.
AB  - Four different extended-spectrum beta -lactamase (ESBL)-producing bacteria from a
      pediatric surgery ward were studied. The presence of TEM-, SHV-, and CTX-M-type
      beta -lactamases was analyzed and the relatedness of the isolates studied with a
      repetitive PCR system (DiversiLab) and pulsed-fi eld gel electrophoresis (PFGE).
      Molecular analysis showed that a clonal dissemination of CTX-M-15-producing
      Escherichia coli and Enterobacter cloacae had occurred.

PMID- 24303911
TI  - Development and preliminary evaluation of a telephone-based mindfulness training
      intervention for survivors of critical illness.
AB  - RATIONALE: Persistent symptoms of psychological distress represent an unmet need
      among intensive care unit (ICU) survivors. OBJECTIVES: We aimed to develop and
      pilot test a simple telephone-based mindfulness training intervention to address
      this population's unique needs. METHODS: Open trial involving survivors of
      medical and surgical critical illness and their informal caregivers, using a
      pretest-posttest design. MEASUREMENTS AND MAIN RESULTS: We developed a six
      session, telephone-delivered, ICU survivor-specific mindfulness intervention
      based on past focus groups, the medical literature, and the precedent of the most
      effective components of existing mindfulness programs. A total of 11 survivors of
      mechanical ventilation were enrolled, together with 2 informal caregivers for
      exploratory purposes. Three patients dropped out before intervention initiation
      because of progressive illness or severe social stressors. Of the 10 remaining
      participants, 8 (80%) completed the program within 7 weeks. Among these eight
      patients and caregivers who completed all study procedures, six (75%) experienced
      improvement in symptoms of psychological distress (anxiety, depression, or post
      traumatic stress disorder). Changes in distress symptoms were correlated with
      improvement in mindfulness qualities, adaptive coping, and emotion regulation.
      Participants reported high satisfaction with the program in postintervention
      interviews. CONCLUSIONS: A new ICU survivor-specific mindfulness training
      intervention delivered by telephone was acceptable and feasible. Changes in
      symptoms of distress were correlated with changes in skills that were targeted by
      the mindfulness program. Controlled trials are needed to further evaluate this
      promising intervention.

PMID- 24303913
TI  - Divergences in trends in child and adult mortality in sub-Saharan Africa: survey
      evidence on the survival of children and siblings.
AB  - This paper provides an overview of trends in mortality in children aged under 5
      and adults between the ages of 15 and 60 in sub-Saharan Africa, using data on the
      survival of the children and siblings collected in Demographic and Health
      Surveys. If conspicuous stalls in the 1990s are disregarded, child mortality
      levels have generally declined and converged over the last 30-40 years. In
      contrast, adult mortality in many East and Southern African countries has
      increased markedly, echoing earlier increases in the incidence of HIV. In recent
      years, adult mortality levels have begun to decline once again in East Africa, in
      some instances before the large-scale expansion of antiretroviral therapy
      programmes. More surprising is the lack of sustained improvements in adult
      survival in some countries that have not experienced severe HIV epidemics.
      Because trends in child and adult mortality do not always evolve in tandem, we
      argue that model-based estimates, inferred by matching indices of child survival
      onto standard mortality schedules, can be very misleading. 

PMID- 24303914
TI  - Pregnancy outcome after hysteroscopic myomectomy.
AB  - The objective of this longitudinal retrospective study was to evaluate the
      influence of submucosal myomas on pregnancy outcome in infertile patients after
      resectoscopic myomectomy. One-hundred and four women with at least a 1-year-long
      history of infertility and the presence of submucosal myomas as the only cause of
      infertility were selected after surgical treatment. Pregnancy, delivery and
      abortion rates were investigated. Patients were divided into three groups
      according to the myoma classification (G0, G1 and G2). Gestational outcomes were
      analyzed in the three groups correlated by size, location and number of fibroids.
      The total pregnancy rate was 85.8% and no difference was shown regarding myoma
      classification (G0 82.05% versus G1 87.09% versus G2 88.2%; p = ns). Pregnancy
      and delivery rates were not significantly related to the number, localization or
      diameter of the fibroids. The abortion rate was not statistically influenced by
      myoma type, but it was significantly inter-related with myomas situated in the
      anterior uterine wall (p = 0.03). Pre-term delivery was significantly influenced
      by myomas localized in the fundic wall (p = 0.02). Caesarean section rates were
      not affected by the characteristics of the myomas. Our results support the idea
      that resectoscopic myomectomy should be offered to infertile women who wish to
      become pregnant independently of their localization and number.

PMID- 24303915
TI  - Global minimum Pt(13)M(20) (M = Ag, Au, Cu, Pd) dodecahedral core-shell clusters.
AB  - In this work, we report finding dodecahedral core-shell structures as the
      putative global minima of Pt13M20 (M = Ag, Au, Cu, Pd) clusters by using the
      basin hopping method and the many-body Gupta model potential to model interatomic
      interactions. These nanoparticles consist of an icosahedral 13-atom platinum core
      encapsulated by a 20 metal-atom shell exhibiting a dodecahedral geometry (and Ih
      symmetry). The interaction between the icosahedral platinum core and the
      dodecahedral shell is analyzed in terms of the increase in volume of the
      icosahedral core, and the strength and stickiness of M-Pt and M-M interactions.
      Low-lying metastable isomers are also obtained. Local relaxations at the DFT
      level are performed to verify the energetic ordering and stability of the
      structures predicted by the Gupta potential finding that dodecahedral core-shell
      structures are indeed the putative global minima for Pt13Ag20 and Pt13Pd20,
      whereas decahedral structures are obtained as the minimum energy configurations
      for Pt13Au20 and Pt13Cu20 clusters. 

PMID- 24303916
TI  - One size doesn't fit all: AF ablation, complications, and patients with
      structural heart disease.

PMID- 24303917
TI  - Identifying QTL and genetic correlations between fur quality traits in mink
      (Neovison vison).
AB  - Mapping of QTL affecting fur quality traits (guard hair length, guard hair
      thickness, density of wool, surface of the fur and quality) and skin length was
      performed in a three-generation mink population (F2 design). In the parental
      generation, Nordic Brown mink were crossed reciprocally with American Black short
      nap mink. In all, 1082 mink encompassing three generations were used for the
      analyses. The mink were genotyped for 104 microsatellites covering all 14
      autosomes. The QTL analyses were performed by least-square regression implemented
      in gridqtl software. Genetic and phenotypic correlations and heritabilities were
      estimated using the average information-restricted maximum-likelihood method.
      Evidence was found for QTL affecting fur quality traits on nine autosomes. QTL
      were detected for guard hair thickness on chromosomes 1, 2, 3, 6 and 13; for
      guard hair length on chromosomes 2, 3 and 6; for wool density on chromosomes 6
      and 13; for surface on chromosomes 7, 12 and 13; for quality on chromosomes 6, 7,
      11 and 13; and for skin length on chromosomes 7 and 9. Proximity of locations of
      QTL for guard hair length, guard hair thickness and for wool density and quality
      suggests that some of the traits are in part under the influence of the same
      genes. Traits under the influence of QTL at close or identical positions also
      were traits that were strongly genotypically correlated. Based on the results of
      correlation analyses, the most important single traits influencing the quality
      were found to be density of wool, guard hair thickness and appearance of the
      surface. 

PMID- 24303918
TI  - Cardiovascular function is better in veteran football players than age-matched
      untrained elderly healthy men.
AB  - The aim of the study was to determine whether lifelong football training may
      improve cardiovascular function, physical fitness, and body composition. Our
      subjects were 17 male veteran football players (VPG; 68.1 +/- 2.1 years) and 26
      healthy age-matched untrained men who served as a control group (CG; 68.2 +/- 3.2
      years). Examinations included measurements of cardiac function, microvascular
      endothelial function [reactive hyperemic index (RHI)], maximum oxygen uptake
      (VO2max), and body composition. In VPG, left ventricular (LV) end-diastolic
      volume was 20% larger (P < 0.01) and LV ejection fraction was higher (P < 0.001).
      Tissue Doppler imaging revealed an augmented LV longitudinal displacement, i.e.,
      LV shortening of 21% (P < 0.001) and longitudinal 2D strain was 12% higher (P <
      0.05), in VPG. In VPG, resting heart rate was lower (6 bpm, P < 0.05), and VO2max
      was higher (18%, P < 0.05). In addition, RHI was 21% higher (P < 0.05) in VPG.
      VPG also had lower body mass index (P < 0.05), body fat percentage, total body
      fat mass, android fat percentage, and gynoid fat percentage (all P < 0.01).
      Lifelong participation in football training is associated with better LV systolic
      function, physical fitness, microvascular function, and a healthier body
      composition. Overall, VPG have better cardiovascular function compared with CG,
      which may reduce their cardiovascular morbidity and mortality.

PMID- 24303919
TI  - Catalytic enantioselective Mannich-type reaction via a chiral silver enolate.
AB  - A catalytic asymmetric Mannich-type reaction of alkenyl trichloroacetates with
      aldimines was achieved using SEGPHOS.AgOTf as the chiral precatalyst and N,N
      diisopropylethylamine as the base precatalyst in the presence of 2,2,2
      trifluoroethanol. Optically active beta-amino ketones with up to >99% ee were syn
      selectively obtained in moderate to high yields via the in situ generated chiral
      silver enolates. 

PMID- 24303920
TI  - The detectability half-life in arthropod predator-prey research: what it is, why
      we need it, how to measure it, and how to use it.
AB  - Molecular gut-content analysis enables detection of arthropod predation with
      minimal disruption of ecosystem processes. Most assays produce only qualitative
      results, with each predator testing either positive or negative for target prey
      remains. Nevertheless, they have yielded important insights into community
      processes. For example, they have confirmed the long-hypothesized role of
      generalist predators in retarding early-season build-up of pest populations prior
      to the arrival of more specialized predators and parasitoids and documented the
      ubiquity of secondary and intraguild predation. However, raw qualitative gut
      content data cannot be used to assess the relative impact of different predator
      taxa on prey population dynamics: they must first be weighted by the relative
      detectability periods for molecular prey remains for each predator-prey
      combination. If this is not carried out, interpretations of predator impact will
      be biased towards those with the longest detectabilities. We review the
      challenges in determining detectability half-lives, including unstated
      assumptions that have often been ignored in the performance of feeding trials. We
      also show how detectability half-lives can be used to properly weight assay data
      to rank predators by their importance in prey population suppression, and how
      sets of half-lives can be used to test hypotheses concerning predator ecology and
      physiology. We use data from 32 publications, comprising 97 half-lives, to
      generate and test hypotheses on taxonomic differences in detectability half-lives
      and discuss the possible role of the detectability half-life in interpreting qPCR
      and next-generation sequencing data. 

PMID- 24303922
TI  - Upregulation of S100P, receptor for advanced glycation end products and ezrin in
      malignant melanoma.
AB  - S100P is a member of the S100 family. Increased levels of S100P have been
      documented in various malignancies. Binding of extracellular S100P to receptor
      for advanced glycation end products (RAGE) or coupling of intracellular S100P
      with a cytoskeletal protein, ezrin, play a crucial role in tumor growth, invasion
      and metastasis. However, little is known about the expression of S100P, RAGE and
      ezrin in malignant melanoma. We immunostained these three molecules in 20 primary
      and 20 metastatic melanomas. Samples of 20 benign nevus pigmentosus and 10 of
      normal skin were tested as controls. The expression levels (percentage of
      positively stained cells) of S100P, RAGE and ezrin were significantly higher in
      melanomas than in nevus pigmentosus. Moreover, slightly but significantly higher
      expression levels were observed in metastatic than in primary melanomas.
      Significant positive correlations were evident between the expression levels of
      S100P and RAGE, S100P and ezrin, and RAGE and ezrin, respectively. In conclusion,
      the coordinate upregulation of S100P, RAGE and ezrin may possibly facilitate
      malignant transformation of melanoma. 

PMID- 24303921
TI  - Intratracheal exposure to Fab fragments of an allergen-specific monoclonal
      antibody regulates asthmatic responses in mice.
AB  - Fab fragments (Fabs) maintain the ability to bind to specific antigens but lack
      effector functions due to the absence of the Fc portion. In the present study, we
      tested whether Fabs of an allergen-specific monoclonal antibody (mAb) were able
      to regulate asthmatic responses in mice. Asthmatic responses were induced in
      BALB/c mice by passive sensitization with anti-ovalbumin (OVA) polyclonal
      antibodies (pAbs) (day 0) and by active sensitization with OVA (days 0 and 14),
      followed by intratracheal (i.t.) challenge with OVA on day 1 and days 28, 29, 30
      and 35. Fabs prepared by the digestion of an anti-OVA IgG1 (O1-10) mAb with
      papain were i.t. administered only once 30 min before antigenic challenge on day
      1 or day 35. The results showed that i.t. administration of O1-10 Fabs with OVA
      markedly suppressed the early and/or late phases of asthmatic responses caused by
      passive and active sensitization. Similar results were obtained when Fabs of anti
      OVA IgG2b mAb (O2B-3) were i.t. administered. In contrast, neither i.t. injection
      of intact 01-10/O2B-3 nor systemic injection of O1-10 Fabs suppressed the
      asthmatic responses. In vitro studies revealed that the capture of OVA by O1-10
      Fabs prevented the subsequent binding of intact anti-OVA pAbs to the captured
      OVA. These results suggest that asthmatic responses may be down-regulated by the
      i.t. exposure to Fabs of an allergen-specific mAb via a mechanism involving the
      capture of allergen by Fabs in the respiratory tract before the interaction of
      intact antibody and allergen essential for the induction of asthmatic responses.

PMID- 24303923
TI  - Peripancreatic tuberculous lymphadenopathy masquerading as pancreatic malignancy:
      a single-center experience.
AB  - BACKGROUND AND AIM: Peripancreatic tuberculous lymphadenopathy is very rare and
      can be misdiagnosed with pancreatic or peripancreatic malignancies. The clinical
      characteristics and treatment outcome have not been well known. Herein, we
      investigated the accuracy of endoscopic ultrasound-guided fine needle aspiration
      (EUS-FNA), clinical features, and treatment outcomes. METHODS: We retrospectively
      analyzed 42 patients diagnosed with peripancreatic tuberculosis between December
      2004 and January 2011 at the tertiary care hospital in Korea. RESULTS: Median age
      was 36 years (interquartile range, 30-55), and female was 66.7% (28/42). Nineteen
      patients (45.2%) had no symptoms, while the others had non-specific various
      symptoms. Thirteen (31.0%) had a previous history of tuberculosis. Initial
      impressions of the mass were pancreatic cancer in 14 (33.3%) and tuberculous
      lymphadenopathy in 13 patients (31.0%). EUS-FNA was performed in all 42 patients,
      with a diagnostic yield of pathologic examinations in 80.5%, polymerase chain
      reaction for tuberculosis in 42.9%, culture in 47.4%, and acid-fast bacilli
      staining in 10.0%. Tuberculosis is confirmed in 28 (66.7%), and probable
      tuberculosis in 14 (33.3%). All patients received anti-tuberculosis treatment, a
      6-months regimen in 12 (28.6%) and a 9-months regimen in 28 (66.7%). Treatment
      response evaluated in 35 patients (83.3%) by computed tomography criteria showed
      complete response in 10 patients (28.6%), partial response in 23 (65.7%), stable
      disease in 1 (2.9%), and progressive disease in 1 (2.9%). CONCLUSIONS:
      Peripancreatic tuberculous lymphadenopathy is frequently mistaken for pancreatic
      malignancy. EUS-FNA can be helpful for an accurate diagnosis. Complete resolution
      of the lesion, however, was not common on following imaging study after
      treatment.

PMID- 24303924
TI  - Differences in bacterial saliva profile between periodontitis patients and a
      control cohort.
AB  - AIM: Periodontitis is a multifactorial disease in which subgingival bacteria play
      an important role in the pathogenesis of the disease. The objective of this study
      was to determine if periodontitis is associated with a characteristic salivary
      bacterial profile. This was accomplished by comparing the bacterial profile of
      saliva from subjects with chronic periodontitis with that of saliva from a
      control cohort. MATERIALS AND METHODS: Stimulated saliva samples from 139 chronic
      periodontitis patients and 447 samples from a control cohort were analysed using
      the Human Oral Microbe Identification Microarray (HOMIM). Frequency and levels
      (mean HOMIM-value) of around 300 bacterial taxa/clusters in samples were used as
      parameters for investigation. Differences at taxon/cluster values between groups
      were analysed using Mann-Whitney U-test with Benjamini-Hochberg correction for
      multiple comparisons. Principal component analysis was used to visualize
      bacterial community profiles obtained by the HOMIM. RESULTS: Eight bacterial
      taxa, including putative periodontal pathogens as Parvimonas micra and Filifactor
      alocis, and four bacterial clusters were identified statistically more frequently
      and at higher levels in samples from periodontitis patients than in samples from
      the control cohort. These differences were independent of the individuals'
      smoking status. CONCLUSIONS: Periodontitis is associated with a characteristic
      bacterial profile of saliva different from that of a control cohort.

PMID- 24303925
TI  - A2E-mediated photochemical modification to fibronectin and its implications to
      age-related changes in Bruch's membrane.
AB  - Lipofuscin accumulates normally with age and is more pronounced in retinal
      dystrophies such as age-related macular degeneration. The major bis-retinoid
      component of lipofuscin is A2E. In addition to cell damage effects by A2E, we
      have previously demonstrated that blue-light-mediated A2E leads to modifications
      in the basement membrane protein laminin. Therefore, the purpose of this study
      was to advance the understanding of A2E photooxidation effects on fibronectin,
      the major glycoprotein of Bruch's membrane. In this study, A2E was irradiated
      with blue light in the presence of a fibronectin peptide consisting of amino
      acids from the integrin binding region. The modification sites were identified
      via LC/MS. Our research indicated that blue light irradiation caused cleavage
      throughout the A2E molecule closest to the pyridinium ring, and attached to the
      fibronectin peptide preferentially at lysine and arginine residues. All of these
      reactions are similar to the Maillard reaction. Altogether this study suggests
      that blue-light-irradiated A2E modifies peptides and forms advance glycation
      endproducts. Furthermore, these results can be used to identify modifications
      that occur in Bruch's membrane in vivo. 

PMID- 24303926
TI  - Revised Healthy Lifestyle-Diet Index and associations with obesity and iron
      deficiency in schoolchildren: The Healthy Growth Study.
AB  - BACKGROUND: The Healthy Lifestyle-Diet Index (HLD-index), previously developed to
      assess the degree of adherence to dietary and lifestyle guidelines for primary
      schoolchildren, was revised according to updated recommendations. Tauhe
      association of the revised HLD-index (R-HLD-index) with obesity and iron
      deficiency (ID) was also examined. METHODS: A representative sample of 2660
      primary schoolchildren from Greece (9-13 years old) participating in the 'Healthy
      Growth Study' was examined. Twelve components related to dietary and lifestyle
      patterns were used to develop the R-HLD-index. Scores from 0 up to 4 were
      assigned to each one of these components, giving a total score ranging from 0 to
      48. The associations between the R-HLD-index, obesity and ID were examined via
      logistic regression analysis. RESULTS: The total score of the R-HLD-index
      calculated for each one of the study participants was found to range between 2
      and 32 units, with higher scores being indicative of a healthier lifestyle and
      better diet quality. After adjusting for potential confounders, logistic
      regression analysis showed that an increase in the R-HLD-index score by one unit
      was associated with 6% lower odds for obesity. However, no significant
      association was observed between the R-HLD-index score and ID. CONCLUSIONS: The R
      HLD-index may be a useful tool for public health policy makers and healthcare
      professionals when assessing diet quality and lifestyle patterns of primary
      schoolchildren. Identification of children with lower scores in the R-HLD-index
      and its individual components could guide tailored made interventions targeting
      specific children and behaviors.

PMID- 24303927
TI  - The effect of nanoparticle properties, detection method, delivery route and
      animal model on poly(lactic-co-glycolic) acid nanoparticles biodistribution in
      mice and rats.
AB  - A review of poly(lactic-co-glycolic) acid (PLGA) nanoparticle (NP)
      biodistribution was conducted with the intent of identifying particle behavior
      for drug delivery applications. Databases such as Science Direct and Web of
      Science were used to locate papers on biodistribution of intravenous (i.v.) and
      orally delivered PLGA NPs in mice and rats. The papers included in the review
      were limited to those that report biodistribution data in terms of % dose
      particles/g tissue in the liver, kidney, spleen, lung, heart and brain. Noted
      trends involved particle behavior based on individual organ, particle size,
      animal model, type of indicator (entrapped versus covalently linked) and method
      of delivery (oral or i.v.). The liver showed the highest uptake of particles in
      mice, and the lung showed the highest uptake in rats. Minimal amounts of
      particles were detected in both the heart and brain of rats and mice. In rats,
      the concentration of particles approached 0% dose/g or decreased significantly
      over 24 h after administration of a single dose of particles. Higher
      concentrations of smaller particles were evident in the liver, kidney and spleen.
      Orally delivered drugs showed little to no uptake within the 24 h analysis when
      compared with i.v. delivered NPs. Differences in particle concentrations between
      rats and mice were also observed as expected when expressed as % dose/g organ.
      Particles with covalently linked indicators showed lower concentrations in
      tissues than particles with physically entrapped indicators. Further research on
      oral delivery of PLGA NPs as well as distribution beyond 24 h is needed to fully
      understand particle behavior in vivo for successful application of NPs in drug
      delivery.

PMID- 24303928
TI  - The first 'emotion' journals.

PMID- 24303929
TI  - Consolidation deficits in traumatic brain injury: the core and residual verbal
      memory defect.
AB  - While memory deficits are consistently found to be a salient problem in
      individuals with moderate to severe traumatic brain injury (TBI), the specific
      memory processes (i.e., encoding, consolidation, and retrieval) underlying the
      verbal memory deficit are disputed in the literature. The current study evaluated
      the recovery of these verbal memory processes over time. A TBI patient group
      evaluated acutely after the injury (baseline) and again at 6 months and 1 year
      post injury was compared to a demographically similar control group evaluated
      only once. The current results replicated previous findings in support of an
      impaired consolidation hypothesis as the primary deficit underlying memory
      impairment in TBI. These deficits are reflected in relatively more rapid
      forgetting through 1 year post injury and relatively less proactive interference
      up to 6 months post injury. 

PMID- 24303931
TI  - Successful weight loss: how information technology is used to lose.
AB  - BACKGROUND: Commercial producers have outpaced traditional academic healthcare in
      terms of novel repackaging of traditional approaches to weight control for online
      delivery. Little is known, however, about consumers' experiences with such
      products and services. We explored ways that people use information technology
      (IT) to facilitate health-related behavioral change. MATERIALS AND METHODS:
      Qualitative methods and grounded theory methodology were used to analyze
      transcripts of audiotaped material from three focus groups, each with 12
      participants. Participants were recruited from an ongoing, community-wide weight
      loss event, who reported regular or frequent use of IT. RESULTS: Participants
      frequently used IT applications for completing functional tasks associated with
      weight loss. In contrast, most participants preferred in-person social support.
      IT applications facilitated integration of behavior change tasks into everyday
      life. Despite easy access to a range of social networking Web sites and tools,
      however, having access to in-person social support was targeted as critical to
      successful weight loss and well-being. To this end, the role of work peers and
      work environments was emphasized by these participants. CONCLUSIONS: In terms of
      patient care, successful health portals may benefit from either developing or
      integrating existing IT applications that save time and/or provide users with
      visual feedback on progress toward goals. IT-delivered resources would likely
      optimize community-based behavioral health interventions that target naturally
      occurring social groups.

PMID- 24303930
TI  - The Cardiovascular Intervention Improvement Telemedicine Study (CITIES):
      rationale for a tailored behavioral and educational pharmacist-administered
      intervention for achieving cardiovascular disease risk reduction.
AB  - BACKGROUND: Hypertension, hyperlipidemia, and diabetes are significant, but often
      preventable, contributors to cardiovascular disease (CVD) risk. Medication and
      behavioral nonadherence are significant barriers to successful hypertension,
      hyperlidemia, and diabetes management. Our objective was to describe the
      theoretical framework underlying a tailored behavioral and educational pharmacist
      administered intervention for achieving CVD risk reduction. MATERIALS AND
      METHODS: Adults with poorly controlled hypertension and/or hyperlipidemia were
      enrolled from three outpatient primary care clinics associated with the Durham
      Veterans Affairs Medical Center (Durham, NC). Participants were randomly assigned
      to receive a pharmacist-administered, tailored, 1-year telephone-based
      intervention or usual care. The goal of the study was to reduce the risk for CVD
      through a theory-driven intervention to increase medication adherence and improve
      health behaviors. RESULTS: Enrollment began in November 2011 and is ongoing. The
      target sample size is 500 patients. CONCLUSIONS: The Cardiovascular Intervention
      Improvement Telemedicine Study (CITIES) intervention has been designed with a
      strong theoretical underpinning. The theoretical foundation and intervention are
      designed to encourage patients with multiple comorbidities and poorly controlled
      CVD risk factors to engage in home-based monitoring and tailored telephone-based
      interventions. Evidence suggests that clinical pharmacist-administered telephone
      based interventions may be efficiently integrated into primary care for patients
      with poorly controlled CVD risk factors.

PMID- 24303932
TI  - Consumer preferences for telemedicine devices and services in South Korea.
AB  - OBJECTIVE: The scope of healthcare has been expanding from caring for sick people
      to keeping people from becoming sick, and telemedicine will play a significant
      role in this new healthcare paradigm. This study investigated consumer
      preferences and willingness to pay for attributes of telemedicine services in
      South Korea. A market simulation was conducted to examine the market shares of
      alternative services and their relationships to the perceived usefulness of
      service types and preferred device types. MATERIALS AND METHODS: Using a conjoint
      survey, we collected data on consumer preferences for six telemedicine service
      attributes. Data analysis used the Bayesian mixed logit model. The market
      simulation estimated the probabilities of a specific service alternative being
      chosen using estimated model coefficients. RESULTS: Wearable devices were the
      most preferred, followed by smart-home and smartphone devices. Consumers
      perceived managing blood glucose to be the most useful telemedicine service,
      followed by monitoring oxygen saturation and blood pressure. The market
      simulation indicated that consumer preferences for device types were associated
      with the types of chronic diseases for which management through telemedicine
      services is perceived to be useful. CONCLUSIONS: As the focus of healthcare moves
      from treating patients to keeping individuals healthy, a key factor for the
      successful deployment of telemedicine services is understanding consumer
      perceptions and attitudes. The results of this study revealed the dynamics of
      consumer preferences with regard to service attributes.

PMID- 24303933
TI  - Efficient synthesis and in vivo incorporation of acridon-2-ylalanine, a
      fluorescent amino acid for lifetime and Forster resonance energy
      transfer/luminescence resonance energy transfer studies.
AB  - The amino acid acridon-2-ylalanine (Acd) can be a valuable probe of protein
      conformational change because it is a long lifetime, visible wavelength
      fluorophore that is small enough to be incorporated during ribosomal
      biosynthesis. Incorporation of Acd into proteins expressed in Escherichia coli
      requires efficient chemical synthesis to produce large quantities of the amino
      acid and the generation of a mutant aminoacyl tRNA synthetase that can
      selectively charge the amino acid onto a tRNA. Here, we report the synthesis of
      Acd in 87% yield over five steps from Tyr and the identification of an Acd
      synthetase by screening candidate enzymes previously evolved from Methanococcus
      janaschii Tyr synthetase for unnatural amino acid incorporation. Furthermore, we
      characterize the photophysical properties of Acd, including quenching
      interactions with select natural amino acids and Forster resonance energy
      transfer (FRET) interactions with common fluorophores such as methoxycoumarin
      (Mcm). Finally, we demonstrate the value of incorporation of Acd into proteins,
      using changes in Acd fluorescence lifetimes, Mcm/Acd FRET, or energy transfer to
      Eu(3+) to monitor protein folding and binding interactions. 

PMID- 24303935
TI  - ADHD, anxiety and sleep: a window to understanding the interplay between sleep,
      emotional regulation and attention in children?

PMID- 24303934
TI  - Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs
      for enhanced photoacoustic and ultrasound imaging.
AB  - Recently, perfluorocarbon (PFC) nanodroplets were introduced as contrast agents
      for imaging and image-guided therapy. For example, in sonography, high-intensity
      ultrasound pulses were used to phase-transition liquid perfluorocarbon to produce
      gas microbubbles. More recently, perfluorocarbon nanodroplets with encapsulated
      gold nanorods were used as dual ultrasound/photoacoustic contrast agents. To
      expedite clinical translation, we synthesized and characterized ICG-loaded
      perfluorocarbon nanodroplets, i.e., constructs comprising biocompatible, nontoxic
      and biologically safe materials. We then demonstrated enhanced photoacoustic
      contrast through optically triggered phase transition of PFC nanodroplets and
      ultrasound contrast from the resulting PFC bubbles. We assessed the quality
      enhancement of photoacoustic and ultrasound images through analysis of contrast
      and contrast-to-noise ratio. We further investigated the changes in image
      contrast due to increased ambient temperature. Our studies suggest that ICG
      loaded perfluorocarbon nanodroplets may become a valuable tool for various
      imaging modalities, and have promising therapeutic applications. 

PMID- 24303936
TI  - Relationship between PPARgamma Pro12Ala gene polymorphism and type 2 diabetic
      nephropathy risk in Asian population: results from a meta-analysis.
AB  - The relationship between peroxisome proliferator-activated receptor gamma
      (PPARgamma) Pro12Ala gene polymorphism and type 2 diabetic nephropathy (T2DN)
      risk in Asians is still unclear. This study was performed to evaluate if there
      was an association between the PPARgamma Pro12Ala gene polymorphism and T2DN risk
      in Asians using meta-analysis. The relevant reports were searched and identified
      from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database)
      on 1 October 2013, and eligible studies were included and synthesized. Ten
      reports were recruited into this meta-analysis for the association of the
      PPARgamma Pro12Ala gene polymorphism with T2DN risk. The Pro12Ala gene
      polymorphism in the Asian population was shown to be not associated with T2DN
      risk (Ala/Ala: OR = 0.67, 95% CI: 0.22-2.00, p = 0.47; Pro/Pro: OR = 1.77, 95%
      CI: 0.82-1.65, p = 0.39; Ala allele: OR = 0.74, 95% CI: 0.47-1.16, p = 0.19). In
      the sensitivity analysis according to Hardy-Weinberg equilibrium (HWE), the
      control source from hospital, the control source from population, the genotyping
      methods using PCR-RFLP, the genotyping methods using Taqman, sample size of case
      (>= 100), the association of the PPARgamma Pro12Ala gene polymorphism with T2DN
      risk was also not found. Interestingly, in the sensitivity analysis according to
      sample size of case (<100), Ala allele was associated with T2DN risk, but not the
      Pro/Pro genotype. However, the sample size for sensitivity analysis according to
      sample size of case (<100) was relatively small and therefore, the results should
      be interpreted with care. In conclusion, the PPARgamma Pro12Ala gene polymorphism
      was not associated with T2DN risk in Asians. However, Ala allele was associated
      with T2DN risk when the sample size of case was less than 100. Nonetheless,
      additional studies are required to firmly establish a correlation between the
      PPARgamma Pro12Ala gene polymorphism and T2DN risk in Asians.

PMID- 24303937
TI  - Role of poly (ADP-ribose)-polymerase and its signaling pathway with renin
      angiotensin aldosterone system in renal diseases.
AB  - Poly(ADP-ribose) polymerase (PARP), a ubiquitous, chromatin-bound enzyme, plays a
      crucial role in many processes, including DNA repair, cell death, metabolism, and
      inflammatory responses, by activating DNA repair pathways responsible for
      cellular survival. Renin-angiotensin-aldosterone system (RAAS) genes encode
      renin, angiotensinogen, angiotensin-converting enzyme, angiotensin type-1
      receptor and aldosterone synthase gene. RAAS is a hormone system which acts on
      multiple physiologic pathways primarily by regulating blood pressure, electrolyte
      and fluid homeostasis in mammals, but also by local autocrine and paracrine
      actions. The current status quo of scientific evidence shows that there might be
      a signaling pathway between PARP and RAAS. Herein, we review the role of PARP and
      its signaling pathways with RAAS in renal diseases.

PMID- 24303938
TI  - Distribution of rat neonatal Fc receptor in the principal organs of neonatal and
      pubertal rats.
AB  - The neonatal Fc receptor (FcRn) mediates the transfer of IgG and albumin, also
      protects them from catabolism. This study characterized the expression of FcRn in
      different organs of neonatal and pubertal rats by reverse transcription-PCR (RT
      PCR) and immunohistochemistry, demonstrates that FcRn is expressed in liver,
      kidney, intestine, heart, lung, spleen, skin and skeletal muscles at varying
      levels post-gestation from d 1 to d 63. This finding is contrary to previous
      studies claiming that FcRn is undetectable in most tissues after weaning. Lungs
      were the predominant organs for FcRn expression, whereas skin, liver and
      intestine are considerably less expressed organs. The expression of FcRn
      fluctuated in all the organs tested, and with a higher frequency before weaning
      compared to puberty. These findings may provide clues for the better
      understanding of FcRn function, and are important for determining the dosage
      levels for IgG and the constant region fragment (Fc)-containing therapeutic
      proteins whose half-life is regulated by FcRn.

PMID- 24303939
TI  - The signaling pathway of stromal cell-derived factor-1 and its role in kidney
      diseases.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1) regulates the trafficking of
      progenitor cell (PGC) during embryonic development, cell chemotaxis, and
      postnatal homing into injury sites. SDF-1 also regulates cell growth, survival,
      adhesion and angiogenesis. However, in different tissues/cells, the role of SDF-1
      is different, such as that it is increased in most of the tumors and associated
      with cancer metastasis, whereas it is essential for the development of
      vasculature. For kidney diseases, its role remains controversial. Signaling
      pathways might be very important in the pathogenesis of kidney diseases. We
      performed this review to provide a relatively complete signaling pathway
      flowchart for SDF-1 to the investigators who were interested in the role of SDF-1
      in the pathogenesis of kidney diseases. Here, we reviewed the signal transduction
      pathway of SDF-1 and its role in the pathogenesis of kidney diseases.

PMID- 24303940
TI  - WNT signaling and chondrocytes: from cell fate determination to osteoarthritis
      physiopathology.
AB  - CONTEXT: Osteoarthritis (OA) is an articular disorder leading to the degradation
      of articular cartilage phenotypical chondrocytes modifications, including the
      acquisition of a fibroblast-like morphology, decreased expression of collagen
      type II, and increased expression of fetal collagen type I, metalloproteinase 13
      and nitric oxide synthase. This promotes matrix degradation and unsuccessful
      cartilage repair. WNT signaling constitutes one of the most critical biological
      processes during cell fate assignment and homeostasis. OBJECTIVES: This review
      aims to give an insight on results from the studies that were interested in the
      involvement of WNT in OA. METHODS: Studies were selected through a pubmed search.
      RESULTS: Recent genetic data showed that aberration in WNT signaling may be
      involved in OA. WNT signals are transduced through at least three cascades: the
      canonical WNT/beta-catenin pathway, the WNT/Ca(2+) pathway and the WNT/planar
      cell polarity pathway. Most of the studies used in-vitro models to elucidate the
      involvement of WNT in the physiopathology of OA. These studies analyzed the
      expression pattern of WNT pathway components during OA such as WNT5, WNT7, co
      receptor LRP, beta-catenin, WNT target genes (c-jun, cyclins) and/or the
      interaction of these components with the secretion of OA most important markers
      such as IL-1, collagens, MMPs. Results from these studies are in favor of a deep
      involvement of the WNT signaling in the physiopathology of OA either by having a
      protective or a destructive role. CONCLUSION: Deeper researches may eventually
      allow scientists to target WNT pathway in order to help develop efficient
      therapeutic approaches to treat OA.

PMID- 24303941
TI  - Cryoablation of AVNRT in children and adolescents: early intervention leads to a
      better outcome.
AB  - INTRODUCTION: Currently, transcatheter cryoablation is a well-established
      technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT)
      in children. In the past decade, many studies have focused on identifying factors
      that may affect acute and long-term outcome, but none has been shown to be
      strongly predictive of treatment success. The aim of our study was to determine
      whether patient age and cryoablation method correlate with acute and long-term
      success. METHODS AND RESULTS: We retrospectively reviewed 202 consecutive
      patients (98 male, mean age 11.5 years; range: 4-20 years) who underwent
      cryoablation for AVNRT at our institution from October 2002 to August 2012.
      Patients were divided into 2 groups according to age: group A <12 years (n = 101)
      and group B >=12 years (n = 101). A single lesion or linear lesion technique was
      employed. A total of 217 cryoablation procedures were performed: 106 (49%) in
      group A and 111 (51%) in group B. All patients were evaluated in our
      postoperative follow-up program. The overall recurrence rate was 10.9% (22/202).
      AVNRT recurrence was significantly lower in group A than in group B (4.95% vs
      16.8%, P = 0.000). No significant differences in recurrence rate were observed
      between groups when using the single lesion versus linear lesion technique. There
      were no permanent cryoablation-related complications. CONCLUSION: Our findings
      show that cryoablation had no complications and a very good success rate. Type of
      cryolesion is not predictive of long-term success, whereas lower recurrence rate
      is achieved when cryoablation is performed at a younger age.

PMID- 24303942
TI  - Extended Huckel method calculation of polarization energies: the case of a
      benzene dimer.
AB  - We adapted Hoffmann's extended Huckel method to an interacting molecular system
      and use this approach to compute the electron affinity and ionization potential
      of benzene dimers. We restrict the added charge to one of the molecules and argue
      that the dimer energy computed in this manner is the relevant energy in any
      meaningful thermally activated hopping rate expression. The dimer electron
      affinity and ionization potential differs from the isolated molecule
      corresponding quantity by what is called polarization energy. The polarization
      energy normally stabilizes the anion and this is particularly relevant for
      benzene, given that its isolated anion is unstable with respect to charge
      detachment. We found that the anionic benzene dimer is only stabilized in certain
      conformations, suggesting that the stabilization of a benzene anion in an
      amorphous environment is very unlikely. The modest computational cost of the
      method makes it a viable alternative to compute the energy of charged molecules
      in amorphous molecular films, a central issue in the problem of charge transport
      in organic electronics. 

PMID- 24303943
TI  - Genome-wide analysis of Italian sheep diversity reveals a strong geographic
      pattern and cryptic relationships between breeds.
AB  - Italy counts several sheep breeds, arisen over centuries as a consequence of
      ancient and recent genetic and demographic events. To finely reconstruct genetic
      structure and relationships between Italian sheep, 496 subjects from 19 breeds
      were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds
      from the Sheep HapMap dataset was also included in the analyses. Genetic
      distances (as visualized either in a network or in a multidimensional scaling
      analysis of identical by state distances) closely reflected geographic proximity
      between breeds, with a clear north-south gradient, likely because of high levels
      of past gene flow and admixture all along the peninsula. Sardinian breeds
      diverged more from other breeds, a probable consequence of the combined effect of
      ancient sporadic introgression of feral mouflon and long-lasting genetic
      isolation from continental sheep populations. The study allowed the detection of
      previously undocumented episodes of recent introgression (Delle Langhe into the
      endangered Altamurana breed) as well as signatures of known, or claimed,
      historical introgression (Merino into Sopravissana and Gentile di Puglia;
      Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese).
      Arguments that would question, from a genomic point of view, the current breed
      classification of Bergamasca and Biellese into two separate breeds are presented.
      Finally, a role for traditional transhumance practices in shaping the genetic
      makeup of Alpine sheep breeds is proposed. The study represents the first
      exhaustive analysis of Italian sheep diversity in an European context, and it
      bridges the gap in the previous HapMap panel between Western Mediterranean and
      Swiss breeds.

PMID- 24303944
TI  - Synthesis of a dicyano abietane, a key intermediate for the anti-inflammatory
      agent TBE-31.
AB  - The synthesis of dicyano abietane 11, a potential precursor to the biologically
      active tricyclic bis-cyano enone 6 (TBE-31), was accomplished in eight steps from
      epoxide 13. The synthesis features a Lewis acid promoted stereoselective
      cyclization of epoxide 13 to generate the tricyclic ring system 12 in one step. 

PMID- 24303945
TI  - Evaluation of a cyclopentane-based gamma-amino acid for the ability to promote
      alpha/gamma-peptide secondary structure.
AB  - We report the asymmetric synthesis of the gamma-amino acid (1R,2R)-2-aminomethyl
      1-cyclopentane carboxylic acid (AMCP) and an evaluation of this residue's
      potential to promote secondary structure in alpha/gamma-peptides. Simulated
      annealing calculations using NMR-derived distance restraints obtained for
      alpha/gamma-peptides in chloroform reveal that AMCP-containing oligomers are
      conformationally flexible. However, additional evidence suggests that an
      internally hydrogen-bonded helical conformation is partially populated in
      solution. From these data, we propose characteristic NOE patterns for the
      formation of the alpha/gamma-peptide 12/10-helix and discuss the apparent
      conformational frustration of AMCP-containing oligomers. 

PMID- 24303946
TI  - Clinical utility of loop-mediated isothermal amplification assay for the
      diagnosis of common alpha herpesvirus skin infections.
AB  - Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification
      method with a high specificity, efficiency and speed. No reports exist regarding
      the usefulness of LAMP for clinically suspected skin infections caused by herpes
      simplex virus (HSV) or varicella zoster virus (VZV). The aim of this study was to
      evaluate the clinical usefulness of LAMP in the diagnosis of common cutaneous
      alpha herpesvirus (HSV type 1 and 2, and VZV) infections. LAMP and real-time
      polymerase chain reaction (PCR) were performed using swab samples collected from
      106 patients with clinically suspected alpha herpesvirus skin infections. The
      results of LAMP performed with DNA extraction did not differ from those performed
      without DNA extraction. The sensitivity of LAMP tested against real-time PCR was
      96% in herpes simplex, 78% in eczema herpeticum, 93% in herpes zoster and 100% in
      varicella. No viral DNA was detected by LAMP in all negative real-time PCR
      samples. Viral DNA load was significantly lower in samples with false-negative
      LAMP results than in the LAMP-positive samples. LAMP enables confirmation of
      clinically suspected cutaneous HSV and VZV infections. However, the sensitivity
      of LAMP is lower than real-time PCR. The accuracy of LAMP may increase if
      sufficient viral DNA is obtained from lesions. LAMP performed without DNA
      extraction remains sensitive; thus, LAMP represents a quick and economical method
      for the diagnosis of common alpha herpesvirus skin infections. 

PMID- 24303948
TI  - Heparin-binding epidermal growth factor-like growth factor: a hepatic stellate
      cell proliferation inducer via ErbB receptors.
AB  - BACKGROUND AND AIM: Heparin-binding epidermal growth factor-like growth factor
      (HB-EGF) has a proliferative effect on several types of cells. However, the role
      of HB-EGF on hepatic stellate cells (HSCs) is not clear. The present study is to
      investigate the regulatory effects of HB-EGF on HSC proliferation and apoptosis.
      METHODS: Activated primary rat HSCs and two HSC cell lines (human LX2 and rat T6)
      were used in this study. Four inhibitors (CRM197 to HB-EGF, AG1478 to epidermal
      growth factor receptor [EGFR], PD98059 to mitogen-activated kinase, and LY294002
      to phosphatidylinositol 3-kinase) were employed to verify the pathway of HB-EGF
      on cell proliferation and apoptosis. RESULTS: HB-EGF expression was significantly
      increased in activated HSCs. HB-EGF increased the expressions of phospho-EGFR and
      ErbB4 receptors, the phosphorylation of extracellular signal-regulated kinase
      (ERK) and Akt. Consequently, HB-EGF stimulated HSC proliferation and suppressed
      HSC apoptosis. Each individual inhibitor specifically inhibited the correlated
      receptor or enzyme and inhibited HSC proliferation and induced its apoptosis.
      CONCLUSIONS: HB-EGF promotes HSC proliferation via activation of the EGFR and
      ErbB4 receptors and, subsequently, via activation of ERK and Akt. Any blockage in
      the chain obstructs the flow from HB-EGF to HSC proliferation. Therefore, HB-EGF
      is a potential therapeutic target in liver fibrosis.

PMID- 24303949
TI  - Deriving static atomic multipoles from the electrostatic potential.
AB  - The description of molecular systems using multipolar electrostatics calls for
      automated methods to fit the necessary parameters. In this paper, we describe an
      open-source software package that allows fitting atomic multipoles (MTPs) from
      the ab initio electrostatic potential by adequate atom typing and judicious
      assignment of the local axis system. By enabling the simultaneous fit of several
      molecules and/or conformations, the package addresses issues of parameter
      transferability and lack of sampling for buried atoms. We illustrate the method
      by studying a series of small alcohol molecules, as well as various conformations
      of protonated butylamine. 

PMID- 24303947
TI  - Analysis of human B-cell responses following ChAd63-MVA MSP1 and AMA1
      immunization and controlled malaria infection.
AB  - Acquisition of non-sterilizing natural immunity to Plasmodium falciparum malaria
      has been shown in low transmission areas following multiple exposures. However,
      conflicting data from endemic areas suggest that the parasite may interfere with
      the induction of effective B-cell responses. To date, the impact of blood-stage
      parasite exposure on antigen-specific B cells has not been reported following
      controlled human malaria infection (CHMI). Here we analysed human B-cell
      responses in a series of Phase I/IIa clinical trials, which include CHMI, using
      candidate virus-vectored vaccines encoding two blood-stage antigens: merozoite
      surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). Previously
      vaccinated volunteers show boosting of pre-existing antigen-specific memory B
      cell (mBC) responses following CHMI. In contrast, unvaccinated malaria-naive
      control volunteers developed an mBC response against MSP1 but not AMA1. Serum IgG
      correlated with the mBC response after booster vaccination but this relationship
      was less well maintained following CHMI. A significant reduction in peripheral
      MSP1-specific mBC was observed at the point of diagnosis of blood-stage
      infection. This was coincident with a reduction in peripheral blood B-cell
      subsets expressing CXCR3 and elevated serum levels of interferon-gamma and CXCL9,
      suggesting migration away from the periphery. These CHMI data confirm that mBC
      and antibody responses can be induced and boosted by blood-stage parasite
      exposure, in support of epidemiological studies on low-level parasite exposure. 

PMID- 24303950
TI  - Characterization of a variant of ERGIC2 transcript.
AB  - ERGIC2 (formerly known as PTX1) is a gene identified by subtractive hybridization
      on the basis that it is expressed in normal human prostate, but not in prostate
      carcinoma. It is unrelated to the gene encoding pituitary homeobox protein (Ptx1
      or Pitx1), which regulates pituitary hormone gene expression. Based on sequence
      homology with the yeast Erv41 protein, it is suggested that the ERGIC2 protein is
      an endoplasmic reticulum (ER) resident protein involved in protein trafficking
      between the ER and Golgi intermediate compartment (ERGIC) and cis-Golgi. However,
      studies from our laboratory and others have shown that it may have other
      functions. In this study, we have identified a variant ERGIC2 transcript with a
      four base deletion at the junction of exons 8-9, resulting in frame shift after
      codon #189. As a result, a truncated protein of 215 residues (24.5 kDa) is
      predicted as compared with the 377-residue (42.6 kDa) wild-type (WT) protein. The
      truncated variant ERGIC2 protein loses 45% of the luminal domain and the
      transmembrane domain near the C-terminus, and this effectively abrogates its
      function as the ERGIC-Golgi protein transport shuttle. The variant, like the WT
      protein, was found to upregulate the heme oxygenase 1 gene, suggesting that it
      may be involved in the oxidative stress pathway.

PMID- 24303951
TI  - A teacher-centered exploration of the relevance of social factors to theory of
      mind development.
AB  - Many accounts of children's Theory of Mind (ToM) development favor a cognitive
      explanation, for example, in terms of mental representational improvements at or
      before 4 years. Here, we investigated whether social factors as rated by a
      child's teacher, are related to ToM development. We tested 82 children of 3-6
      years on each of four ToM tasks, and their class teacher completed a social
      questionnaire about each child's playing behavior, sharing, talkativeness,
      confidence, aggressiveness and outgoingness. A measure of task memory and the
      child's gender were also recorded. Here, children generally passed ToM tasks
      after 5 years-old, but no one gender performed reliably better than the other.
      Teacher-rated confidence and playing behavior were correlated to ToM. But in a
      regression analysis, these were replaced by teacher-rated talkativeness; with age
      and memory given primacy in both sets of analyses. It is concluded that
      maturation and cognitive factors may well have primacy but social factors,
      facilitated during early primary education, must also be given a role in ToM
      development.

PMID- 24303952
TI  - Association between cognitive impairments and anxiety disorders following
      traumatic brain injury.
AB  - This study examined the association between cognitive impairment and anxiety
      disorders following traumatic brain injury (TBI). Sixty-six participants
      recruited from a rehabilitation hospital completed the Structured Clinical
      Interview for the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders
      Fourth Edition) and cognitive tests at one year post injury. Prevalence of
      anxiety disorder was 27.3%. Logistic regression analyses revealed that the
      attention/working memory, information processing, and executive functions models
      were significantly associated with anxiety disorder. The memory model was not
      significant. Processing speed emerged as the strongest model associated with
      anxiety disorder. The role of cognitive impairment in the etiology of anxiety
      disorders after TBI is discussed, and treatment implications are explored. 

PMID- 24303953
TI  - Fetal autopsy findings of cardiofaciocutaneous syndrome with a unique BRAF
      mutation.
AB  - Cardiofaciocutaneous (CFC) syndrome is a RASopathy phenotypically characterized
      by facial, cardiac, and ectodermal abnormalities. The extent to which this
      phenotype is expressed in the affected fetus is unclear, and a better
      understanding of the fetal autopsy findings in CFC syndrome could facilitate
      diagnosis and understanding of the developmental effects of dysregulated BRAF
      activity. Here we describe the fetal autopsy findings in a case of CFC syndrome
      in a 17-week fetus with a novel BRAF mutation that demonstrates potential
      similarities and differences with the postnatal presentation of CFC syndrome.

PMID- 24303955
TI  - Reflections on 2013.

PMID- 24303954
TI  - Crevicular fluid biomarkers and periodontal disease progression.
AB  - AIM: Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers
      as predictors of periodontal disease progression (PDP). MATERIALS AND METHODS: In
      this study, 100 individuals participated in a 12-month longitudinal investigation
      and were categorized into four groups according to their periodontal status. GCF,
      clinical parameters and saliva were collected bi-monthly. Subgingival plaque and
      serum were collected bi-annually. For 6 months, no periodontal treatment was
      provided. At 6 months, patients received periodontal therapy and continued
      participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8,
      MMP-9, Osteoprotegerin, C-reactive Protein and IL-1beta. Differences in median
      levels of GCF biomarkers were compared between stable and progressing
      participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was
      used to evaluate the ability of oral biomarkers to classify patients as either
      stable or progressing. RESULTS: Eighty-three individuals completed the 6-month
      monitoring phase. With the exception of GCF C-reactive protein, all biomarkers
      were significantly higher in the PDP group compared to stable patients.
      Clustering analysis showed highest sensitivity levels when biofilm pathogens and
      GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86).
      CONCLUSIONS: Signature of GCF fluid-derived biomarkers combined with pathogens
      and clinical measures provides a sensitive measure for discrimination of PDP
      (ClinicalTrials.gov NCT00277745).

PMID- 24303957
TI  - Supermarket own brand foods: lower in energy cost but similar in nutritional
      quality to their market brand alternatives.
AB  - BACKGROUND: The present study aimed to compare the nutritional quality (NQ) and
      energy costs (EC) (L MJ(-1) ) of own brand (OB) versus market brand (MB) foods in
      2010 and 2012. METHODS: A list of processed foods (n = 32) was identified based
      on the most frequently consumed foods in the UK. Total fat, saturated fat,
      sugars, salt and energy density (ED) (kJ g(-1) ) in 2010 and 2012 were compared
      for six OB and one MB version of each food using a NQ scoring method based on the
      Food Standards Agency's Traffic Light System (TLS). Additional information
      (fruit, vegetable and nut content; protein; fibre and sodium) was recorded in
      2012, and NQ was assessed using the Food Standards Agency's nutrient profiling
      model (NPM). The EC of the food baskets (FB) was compared in 2010 and 2012.
      RESULTS: There were no differences in overall NQ between OB and MB FB in 2010
      (TLS, P = 0.978) or 2012 (TLS, P = 0.840; NPM, P = 0.696). However, the MB FB was
      highest in EC in 2010 and 2012 (both P < 0.001). There was an inverse
      relationship between the ED and EC of the MB foods in 2010 (r = -0.484; P =
      0.005) and 2012 (r = -0.452; P = 0.009). CONCLUSIONS: The MB FB was higher in EC
      than the OB FB in 2010 and 2012 but not superior in overall NQ based on both the
      TLS and NPM.

PMID- 24303958
TI  - Non-parametric three-way mixed ANOVA with aligned rank tests.
AB  - Research problems that require a non-parametric analysis of multifactor designs
      with repeated measures arise in the behavioural sciences. There is, however, a
      lack of available procedures in commonly used statistical packages. In the
      present study, a generalization of the aligned rank test for the two-way
      interaction is proposed for the analysis of the typical sources of variation in a
      three-way analysis of variance (ANOVA) with repeated measures. It can be
      implemented in the usual statistical packages. Its statistical properties are
      tested by using simulation methods with two sample sizes (n = 30 and n = 10) and
      three distributions (normal, exponential and double exponential). Results
      indicate substantial increases in power for non-normal distributions in
      comparison with the usual parametric tests. Similar levels of Type I error for
      both parametric and aligned rank ANOVA were obtained with non-normal
      distributions and large sample sizes. Degrees-of-freedom adjustments for Type I
      error control in small samples are proposed. The procedure is applied to a case
      study with 30 participants per group where it detects gender differences in
      linguistic abilities in blind children not shown previously by other methods.

PMID- 24303959
TI  - Reaching 1 m deep on Mars: the Icebreaker drill.
AB  - The future exploration of Mars will require access to the subsurface, along with
      acquisition of samples for scientific analysis and ground-truthing of water ice
      and mineral reserves for in situ resource utilization. The Icebreaker drill is an
      integral part of the Icebreaker mission concept to search for life in ice-rich
      regions on Mars. Since the mission targets Mars Special Regions as defined by the
      Committee on Space Research (COSPAR), the drill has to meet the appropriate
      cleanliness standards as requested by NASA's Planetary Protection Office. In
      addition, the Icebreaker mission carries life-detection instruments; and in turn,
      the drill and sample delivery system have to meet stringent contamination
      requirements to prevent false positives. This paper reports on the development
      and testing of the Icebreaker drill, a 1 m class rotary-percussive drill and
      triple redundant sample delivery system. The drill acquires subsurface samples in
      short, approximately 10 cm bites, which makes the sampling system robust and
      prevents thawing and phase changes in the target materials. Autonomous drilling,
      sample acquisition, and sample transfer have been successfully demonstrated in
      Mars analog environments in the Arctic and the Antarctic Dry Valleys, as well as
      in a Mars environmental chamber. In all environments, the drill has been shown to
      perform at the "1-1-100-100" level; that is, it drilled to 1 m depth in
      approximately 1 hour with less than 100 N weight on bit and approximately 100 W
      of power. The drilled substrate varied and included pure ice, ice-rich regolith
      with and without rocks and with and without 2% perchlorate, and whole rocks. The
      drill is currently at a Technology Readiness Level (TRL) of 5. The next
      generation Icebreaker drill weighs 10 kg, which is representative of the
      flightlike model at TRL 5/6.

PMID- 24303960
TI  - Development of maternal and neonatal composite outcomes for trials evaluating
      management of late-onset pre-eclampsia.
AB  - OBJECTIVE: Pre-eclampsia is associated with significant maternal and neonatal
      complications, and delivery is often expedited to minimise complications. For
      randomised trials evaluating interventions in women with late-onset (>34 weeks)
      mild to moderate pre-eclampsia, no single outcome has been identified to be the
      most clinically important. Existing composite outcomes with more than one
      clinically relevant endpoint to evaluate interventions in pre-eclampsia provide
      limited justification for selection of the components. Our objective was to
      develop robust, valid composite maternal and neonatal outcome measures for
      clinical trials evaluating interventions in women with late-onset mild and
      moderate pre-eclampsia. STUDY DESIGN: A two-generational Delphi method was used
      to identify these clinically important maternal and neonatal outcomes. Composite
      outcomes were developed based on biological plausibility, independence from each
      other, frequency of occurrence and level of importance. RESULTS: The final
      maternal composite outcome included maternal death, eclampsia, stroke or
      reversible ischaemic neurological deficit, pulmonary oedema, major obstetric
      haemorrhage, need for positive inotropic support, haemolysis, elevated liver
      enzymes and low platelets syndrome and placental abruption; and the neonatal
      composite outcome included neonatal death, respiratory distress syndrome needing
      ventilator support and neurological outcomes as cystic periventricular
      leukomalacia and grade III/IV intraventricular haemorrhage. CONCLUSION: The
      composite outcomes developed will enable clinical trials to provide robust
      estimates on the effectiveness of the interventions in women with mild to
      moderate late onset pre-eclampsia to inform clinical practice. Caution is needed
      in the interpretation of composite outcomes due to variation in the importance of
      individual components.

PMID- 24303961
TI  - Toll-like receptors signaling in glomerular diseases.
AB  - Toll-like receptors (TLRs) are pattern-recognition receptors that recognize
      microbial/vial-derived components that trigger innate immune response, which
      indicate these molecules play a role in host defense against infection. The
      infection often precedes numerous disorders including glomerular diseases
      (glomerulonephritis (GN)). It is reported that TLRs are also involved in the risk
      and progression of GN, and TLRs may be potential therapeutic targets for GN. To
      date, a number of studies have found that TLRs are involved in the pathogenesis
      of GN. There is a paucity of reviews in the literature discussing signaling
      pathways and gene expression for TLRs in GN. This review was performed to provide
      a relatively complete signaling pathway flowchart for TLRs to the investigators
      who were interested in the roles of TLRs in the pathogenesis of GN. In the past
      decades, some studies were also performed to explore the association of TLRs gene
      expression with the risk of GN. However, the role of TLRs in the pathogenesis of
      GN remains controversial. Here, the signal transduction pathways of TLRs and its
      role of gene expression in the pathogenesis of GN were reviewed.

PMID- 24303962
TI  - RNF13 protein regulates endoplasmic reticulum stress induced apoptosis in
      dopaminergic SH-SY5Y cells by enhancing IRE1alpha stability.
AB  - Any interruption in the folding capacity of endoplasmic reticulum (ER) may result
      in inducing ER stress which would initiate an adaptive signaling mechanism called
      Unfolded Protein Response (UPR) in order to restore homeostasis, failing to which
      would initiate signaling pathway leading to death of the cell. Finding new
      mediators could help better understand the molecular mechanisms of ER stress
      induced apoptosis. Our lab initiated a genetic screen method using retroviral
      insertion mutation system to look for genes whose inactivation would confer
      resistance to apoptosis. In our previous findings, Ring finger protein 13 (RNF13)
      was identified whose down-regulation conferred survival against ER stress-induced
      apoptosis. Our previous results also showed important role of RNF13 in apoptotic
      signaling in 293T cells as a result of strong RNF13-IRE1alpha interaction. In
      current study, using SH-SY5Y cells, overexpression of RNF13 in apoptosis assays
      and RT-PCR analysis has shown to induce apoptosis as well as splicing of X-box
      binding Protein 1 (XBP1) confirming its role in ER stress mediated cell death in
      this cell line as well. Western blot analysis has revealed that overexpression of
      both N-terminal as well as C-terminal tagged RNF13 resulted in activation of c
      Jun N-terminal kinase (JNK) in SH-SY5Y cells. Our co-immunoprecipitation assays
      in SH-SY5Y cells also showed a strong interaction of RNF13 with IRE1alpha.
      Finally, Cycloheximide chase experiment exhibited that RNF13-IRE1alpha
      interaction increased the stability of IRE1alpha. Altogether, our data suggest
      that RNF13 may act as an important regulator of IRE1alpha, mediating ER stress
      mediated apoptosis in neuroblastoma SH-SY5Y cells.

PMID- 24303963
TI  - Flexible and transparent dielectric film with a high dielectric constant using
      chemical vapor deposition-grown graphene interlayer.
AB  - We have devised a dielectric film with a chemical vapor deposited graphene
      interlayer and studied the effect of the graphene interlayer on the dielectric
      performance. The highly transparent and flexible film was a
      polymer/graphene/polymer 'sandwich-structure' fabricated by a one-step transfer
      method that had a dielectric constant of 51, with a dielectric loss of 0.05 at 1
      kHz. The graphene interlayer in the film forms a space charge layer, i.e., an
      accumulation of polarized charge carriers near the graphene, resulting in an
      induced space charge polarization and enhanced dielectric constant. The
      characteristic of the space charge layer for the graphene dielectric film, the
      sheet resistance of the graphene interlayer, was adjusted through thermal
      annealing that caused partial oxidation. The dielectric film with higher sheet
      resistance due to the oxidized graphene interlayer had a significantly lower
      dielectric constant compared to that with the graphene with lower interlayer
      sheet resistance. Oxidizing the graphene interlayer yields a smaller and thinner
      space charge density in the dielectric film, ultimately leading to decreased
      capacitance. Considering the simplicity of the fabrication process and high
      dielectric performance, as well as the high transparency and flexibility, this
      film is promising for applications in plastic electronics. 

PMID- 24303964
TI  - Update on narrow band imaging in disorders of the upper gastrointestinal tract.
AB  - With the ever-increasing concern regarding morbidity and mortality associated
      with diseases of the gastrointestinal tract, the importance of an effective and
      efficient diagnostic tool cannot be overstated. The standard of care currently is
      an examination using conventional white light endoscopy. This approach may
      occasionally overlook areas exhibiting a premalignant change. Numerous image
      enhanced modalities have been recently introduced. Narrow band imaging (NBI)
      appears to be the most prominent of these and perhaps the most commonly used.
      Thepresent review will focus on some of the newer studies on NBI and its utility
      in the diagnosis of malignant, pre-malignant and chronic inflammatory conditions
      of the upper gastrointestinal tract. 

PMID- 24303966
TI  - Shlomo Stern (1928-2013) - visionary leader with great legacy in memoriam.

PMID- 24303967
TI  - P-wave morphology is associated with echocardiographic response to cardiac
      resynchronization therapy in MADIT-CRT patients.
AB  - BACKGROUND: In this study we hypothesized that signs of atypical atrial
      activation would be associated with cardiac resynchronization therapy (CRT)
      response in patients with mildly symptomatic heart failure (CHF), left
      ventricular dysfunction, and wide QRS complex. METHODS: Patients included in the
      CRT-D arm in MADIT-CRT were studied (n = 892). Unfiltered signal-averaged P waves
      were analyzed to determine orthogonal P-wave morphology (typical morphologies
      were predefined as having positive signals in Leads X and Y and a negative or
      negative-positive signal in Lead Z. All other patterns were classified as
      atypical). The association between P-wave morphology and data on
      echocardiographic response at 1 year was analyzed. RESULTS: Atypical P-wave
      morphology was found in 21% (n = 186) of the patients at baseline. Patients with
      atypical P-wave morphology were more often female (31% vs. 24%, P = 0.025), had
      lower BMI (28 +/- 5 kg/m(2) vs. 29 +/- 5 kg/m(2) , P = 0.008), had more ischemic
      CHF (60% vs. 52%, P = 0.026) and had smaller left atrial volumes (90 +/- 20 mL
      vs. 94 +/- 22 mL, P = 0.034). Atypical P-wave morphology at baseline was
      associated with superior response to CRT at 1 year with a larger reduction in
      left ventricular end-diastolic volume (-23 +/- 12% vs. -20 +/- 11%, P = 0.009),
      left ventricular end-systolic volume (-36 +/- 16% vs. -31 +/- 16%, P = 0.006),
      and left atrial volume (-31 +/- 12% vs. -27 +/- 12%, P = 0.005), with a slightly
      larger absolute increase in left ventricular ejection fraction (LVEF) (12 +/- 5%
      vs. 11 +/- 5%, P = 0.009). These associations were found to be independent of
      traditional predictors. CONCLUSION: The presence of atypical P-wave morphology
      recorded is independently associated with a favorable echocardiographic cardiac
      remodeling response to CRT.

PMID- 24303968
TI  - U wave features in body surface potential mapping in post-myocardial infarction
      patients.
AB  - BACKGROUND: The data on U wave features in post-myocardial infarction (MI) remain
      sparse. We employed 120-lead body surface potential mapping (BSPM) to explore the
      U wave in patients with remote MI. METHODS: Sixty post-MI patients and 46 healthy
      controls were examined. After signal averaging, the polarity changes of U wave
      related to the T wave were analyzed, and the spatial and temporal U wave
      parameters were computed. RESULTS: Four types of patterns based on T and U
      polarity were recognized. A pattern with positive T and U waves was related to
      better ventricular function. The study groups did not differ as regards to Tend
      Uapex and Tapex-Uapex intervals whereas Uapex-Uend was significantly longer in MI
      patients (110 +/- 20 ms vs. 100 +/- 13 ms, P = 0.004). MI patients had
      significantly higher U wave maximum amplitude (70 +/- 30 MUV vs. 50 +/- 20 MUV, P
      < 0.001), and U integral area (3.96 +/- 1.50 MUV.s vs. 3.17 +/- 0.99 MUV.s, P =
      0.002), but lower corresponding T wave parameter values, thus resulting into
      higher U/T maximum amplitude and area ratios (0.16 +/- 0.10 vs. 0.09 +/- 0.04, P
      < 0.001; and 0.13 +/- 0.06 vs. 0.09 +/- 0.03, P < 0.001). In comparison to 12
      lead ECG, BSPM covering the entire thorax enhanced the detection of U waves.
      CONCLUSION: MI tends to increase the U amplitude and prolong the later part of U
      wave duration thus augmenting the U wave. The size and location of infarction
      were associated with specific T and U wave polarity patterns.

PMID- 24303969
TI  - Fragmented QRS complexes are associated with increased left ventricular mass in
      patients with essential hypertension.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is an independent predictor of
      poor prognosis in patients with hypertension. In hypertensive hypertrophy, the
      pathophysiological mechanism is the accumulation of collagen in the myocardium.
      Fragmented QRS (fQRS) complexes are associated with myocardial fibrosis. METHODS:
      The study population included 90 patients with hypertension and a normal coronary
      angiogram. The fQRS was defined as the presence of an additional R wave (R'),
      notching of the R or S wave, or the presence of fragmentation in two contiguous
      leads corresponding to a major coronary artery. Echocardiographic examinations
      were performed according to the recommendations of the American Society of
      Echocardiography. RESULTS: Forty-five patients who had fQRS and were suitable for
      the study criteria were compared with 45 age- and gender-matched patients who did
      not have fQRS according to demographic data and echocardiographic findings. The
      left ventricular (LV) mass index (g/m(2) ) was significantly higher (P < 0.001)
      in the group with fQRS. The wall thickness, diameter, volume, and ejection
      fraction (EF) were higher in this group (P < 0.001). Concentric and eccentric
      hypertrophy were also higher in this group (P < 0.001). In the logistic
      regression analysis, fQRS on ECG was an indicator of LVH in hypertensive patients
      (B = 0.064; P < 0.001; odds ratio = 1.066; 95% confidence interval = 1.041-1.092)
      CONCLUSION: The LV mass index of the hypertensive patients who had fQRS on their
      ECGs was significantly higher than that of the patients who did not, and fQRS on
      ECG was an important indicator of LVH in hypertensive patients.

PMID- 24303970
TI  - Right-ventricular enlargement in arrhythmogenic right-ventricular cardiomyopathy
      is associated with decreased QRS amplitudes and T-wave negativity.
AB  - BACKGROUND: Arrhythmogenic right-ventricular cardiomyopathy (ARVC) can lead to RV
      dilatation. We hypothesized that electrocardiographic characteristics including
      QRS amplitudes in the extremity- and precordial leads, the S amplitude in lead V1
      , and extent of T-wave negativity over the precordial leads are related to RV
      dilatation in this condition. METHODS: In 42 ARVC patients and 42 controls, we
      correlated total QRS amplitude in the extremity leads (?QRSext ), precordial
      leads (?QRSprec ) and in all leads (?QRStot : summation of ?QRSext and ?QRSprec
      ), S amplitude in lead V1 and the extent of T-wave inversion in the precordial
      leads (V1 vs. beyond V1 ) with RV end diastolic diameter (RVEDD) by
      echocardiography. RESULTS: In the ARVC group, the mean age was 46 +/- 14 years,
      31 patients were male, 28 had an implantable cardioverter defibrillator (ICD),
      and 7 had a LV ejection fraction (EF) < 55%. The control group was age- and
      gender matched to the ARVC cohort. In contrast to controls, the ?QRSext
      (regression coefficient (RC), -0.29; P = 0.020), ?QRSprec (RC, -0.20; P = 0.015),
      and ?QRStot (RC, -0.14; P = 0.009) were lower with RV dilatation in ARVC. S
      amplitude in lead V1 was not related to RV diameter (RC, -0.98; P = 0.088).
      Precordial T-wave inversion beyond lead V1 (V2 -V6 ) was associated with a larger
      RV diameter (RC, 8.58; P = 0.012). CONCLUSIONS: Summed QRS amplitudes in the
      extremity and precordial leads, and T-wave inversion beyond lead V1 are
      associated with RV dilatation in patients with ARVC.

PMID- 24303971
TI  - Performance of an external transtelephonic loop recorder for automated detection
      of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Although atrial fibrillation (AF) is the most commonly encountered
      arrhythmia, some of the properties make its detection challenging. In daily
      practice, underdiagnosis can lead to less effective treatment in prevention of
      stroke. Based on data from studies on treatment of AF, more intensive follow-up
      strategies, including 7-day Holter recording, 30-day event recording, and even
      implantable cardiac monitoring devices, are suggested. The study purpose is to
      evaluate the performance of a continuous single-channel loop recorder with
      automatic AF detection and transtelephonic electrocardiogram (ECG) transmission
      capabilities. METHODS AND RESULTS: A consecutive cohort of 153 patients admitted
      to the stroke unit with a presumptive diagnosis of ischemic cerebrovascular
      accident was screened for AF. Twenty-four-hour rhythm observation was performed
      using a single-channel external loop recorder (ELR) configured for automated AF
      detection. A total of 45 patients with a known history of AF, AF on the admission
      ECG, or incomplete registrations were excluded. Extensive additional frequency
      based settings were used to establish a reference registration. In total, 2923
      recordings were transmitted. We evaluated all events, of which 1190 were
      designated by the device as AF. The sensitivity, specificity, PPV, and NPV for
      identifying AF using the ELR were, respectively, 93%, 51%, 5%, and 99%.
      CONCLUSIONS: In this ELR validation study, the dedicated AF detection algorithm
      showed to be highly sensitive but not specific for AF. Applicability of an ELR
      might be limited for efficacious detection of AF, as manual verification is
      mandatory for a vast amount of recordings.

PMID- 24303972
TI  - Asystole in course of epileptic episode.
AB  - A subgroup of patients with epilepsy die suddenly and ictal bradycardia (IB) has
      been implicated. We describe a 63-year-old man with diagnosis of refractory
      epilepsy. The patient had long video and EEG/ECG recordings (48 hours) of
      wakefulness and abnormal sleep due to the presence of seven ictal events, which
      are associated with complex partial seizures that start on the temporal region.
      The patient presented a severe dysautonomia ictal, at 10-15 seconds of the start
      of the event is observed bradycardia and after 25 seconds occurs asystole for 15
      seconds. Dual-chamber pacemaker was implanted with improvement. 

PMID- 24303973
TI  - Licorice-induced severe hypokalemia with recurrent torsade de pointes.
AB  - A 38-year-old obese woman presented with recurrent polymorphic ventricular
      tachycardia secondary to persistent hypokalemia necessitating more than 40 DC
      shocks. All endocrine investigations for hypokalemia were negative with
      impression of "mysterious hypokalemia." On repeated inquiry, a hidden history of
      licorice use was elicited causing persistent hypokalemia. The case highlights a
      life threatening complication of licorice use. In addition, it reiterates the
      importance of repeated history taking in a patient with undiagnosed hypokalemia
      and torsade de pointes which avoided a device therapy. 

PMID- 24303974
TI  - Deletion variant near ZNF389 is associated with control of ovine lentivirus in
      multiple sheep flocks.
AB  - Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries
      that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep.
      There is no preventive vaccine and no cure, but breed differences suggest marker
      assisted selective breeding might improve odds of infection and control of OvLV
      post-infection. Although variants in TMEM154 have consistent association with
      odds of infection, no variant in any gene has been associated with host control
      of OvLV post-infection in multiple animal sets. Proviral concentration is a live
      animal diagnostic measure of OvLV control post-infection related to severity of
      OvLV-induced lesions. A recent genome-wide association study identified a region
      including four zinc finger genes associated with proviral concentration in one
      Rambouillet flock. To refine this region, we tested additional variants and
      identified a small insertion/deletion variant near ZNF389 that showed consistent
      association with proviral concentration in three animal sets (P < 0.05). These
      animal sets contained Rambouillet, Polypay and crossbred sheep from multiple
      locations and management conditions. Strikingly, one flock had exceptionally high
      prevalence (>87%, including yearlings) and mean proviral concentration (>950
      copies/MUg), possibly due to needle sharing. The best estimate of proviral
      concentration by genotype, obtained from all 1310 OvLV-positive animals tested,
      showed insertion homozygotes had less than half the proviral concentration of
      other genotypes (P < 0.0001). Future work will test additional breeds, management
      conditions and viral subtypes, and identify functional properties of the
      haplotype this deletion variant tracks. To our knowledge, this is the first
      genetic variant consistently associated with host control of OvLV post-infection
      in multiple sheep flocks.

PMID- 24303975
TI  - Evaluation of the antihistamine effects of olopatadine and levocetirizine during
      a 24-h period: a double-blind, randomized, cross-over, placebo-controlled
      comparison in skin responses induced by histamine iontophoresis.
AB  - The antihistamine effects of olopatadine and levocetirizine, in standard-dose
      application described in their information (5 mg twice a day for olopatadine; 5
      mg once daily for levocetirizine), were examined from 11.5 to 24 h after
      application. The test was designed in a double-blind, randomized, cross-over,
      placebo-controlled study of 12 healthy volunteers on histamine-induced flare and
      wheal response using an iontophoresis technique. The suppressive effect of
      olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for
      24 h after dosing. Both drugs inhibited flare induced by histamine iontophoresis
      almost completely until 24 h after the first administration. Suppression of the
      0.2-mA-induced wheal response by levocetirizine, taken once daily, decreased with
      time, although 0.1-mA-induced flare was almost completely suppressed by the drug.
      Olopatadine completely suppressed even the wheal response induced by a 0.2-mA
      histamine iontophoresis. Compared with the placebo, the two drugs significantly
      suppressed the subjective itching assessed by visual analog scale at all
      intervals. There were no significant differences in subjective drowsiness and
      objective cognitive function between drug- and placebo-treated subjects. These
      results demonstrate that olopatadine seems to be more potent than levocetirizine
      when administrated in a standard dose. In conclusion, mild to moderate urticaria
      could be controlled by standard application as described in their information. On
      the other hand, severe urticaria could be managed by a standard application of
      olopatadine, but levocetirizine may need an additional dose to control severe
      urticaria. 

PMID- 24303976
TI  - Artificially accelerating the reversal of desertification: cyanobacterial
      inoculation facilitates the succession of vegetation communities.
AB  - Desertification has been recognized as a global environmental problem, and one
      region experiencing ongoing desertification is the eastern edge of Qubqi Desert
      (Inner Mongolia). To investigate the facilitating effects of cyanobacterial
      inoculation technology on the desertification control along this steppe-desert
      transition region, artificial cyanobacterial crusts were constructed with two
      filamentous cyanobacteria 3 and 8 years ago combined with Salix planting. The
      results showed that no crusts formed after 3 years of fixation only with Salix
      planting, whereas after cyanobacterial inoculation, the crusts formed quickly and
      gradually succeed to moss crusts. During that course, topsoil environments were
      gradually improved, providing the necessary material basis for the regeneration
      of vascular plants. In this investigation, total 27 species of vascular plants
      had regenerated in the experimental region, mainly belonging to Asteraceae,
      Poaceae, Chenopodiaceae and Leguminosae. Using space time substitution, the
      dominant species along with the application of cyanobacterial inoculation
      technology succeeded from Agriophyllum squarrosum ultimately to Leymus chinensis.
      In addition, it was found that the shady side of the dunes is more conducive to
      crust development and succession of vegetation communities. Conclusively, our
      results indicate artificial cyanobacterial inoculation technology is an effective
      and desirable path for desertification control. 

PMID- 24303977
TI  - Usefulness of QuantiFERON(r)-TB Gold test in psoriatic patients under treatment
      with tumour necrosis factor blockers.
AB  - OBJECTIVE: Infliximab is a human/mouse chimeric anti-tumour necrosis factor (TNF)
      alpha antibody that is effective in the management of psoriasis. Anti-TNF
      treatments may reactivate latent tuberculosis infection (LTBI); therefore,
      screening for LTBI is mandatory before starting any anti-TNF-alpha therapy. The
      aim of this study is to evaluate the usefulness of the QuantiFERON(r)-TB Gold
      (QFT-G) test in psoriatic patients under treatment with infliximab. RESEARCH
      DESIGN AND METHODS: A retrospective study had been performed on patients affected
      by psoriasis who had been treated with infliximab from 2003 to 2012 at a single
      centre. MAIN OUTCOMES MEASURES: QFT-G was tested by a standard TB enzyme-linked
      immunosorbent assay, based on detection of interferon-gamma release from
      sensitized leucocytes exposed to the synthetic Mycobacterium tuberculosis
      antigens at baseline and every 6 months until the end of treatment. RESULTS: A
      total of 140 patients were included. At baseline, 7 QFT-G tests were positive and
      133 tests were negative. Of the 133 patients, 11 (8%) who were negative at
      baseline became QFT-G test positive during treatment. Of those 11 patients, 5 had
      a reversion during treatment. Of the 133 patients, 122 (92%) who were negative at
      baseline remained negative. CONCLUSIONS: It was found that the development of
      positive QFT-G tests, observed in 8% treated with infliximab, was not associated
      with pulmonary or extra-pulmonary tuberculosis.

PMID- 24303978
TI  - Cerebellar continuous theta-burst stimulation affects motor learning of voluntary
      arm movements in humans.
AB  - In this study we investigated in healthy subjects whether continuous theta-burst
      stimulation (cTBS) over the lateral cerebellum alters motor practice and
      retention phases during ipsilateral index finger and arm reaching movements. In
      12 healthy subjects we delivered cTBS before repeated index finger abductions or
      arm reaching movements differing in complexity (reaching-to-grasp and reaching-to
      point). We evaluated kinematic variables for index finger and arm reaching
      movements and changes in primary motor cortex (M1) activity tested with
      transcranial magnetic stimulation. Peak acceleration increased during motor
      practice for index finger abductions and reaching-to-grasp movements and
      persisted during motor retention. Peak acceleration decreased during motor
      practice for reaching-to-point movements and the decrease remained during motor
      retention. Cerebellar cTBS left the changes in peak acceleration during motor
      practice for index finger abductions and reaching-to-grasp arm movements
      unchanged but reduced peak acceleration at motor retention. Cerebellar cTBS
      prevented the decrease in peak acceleration for reaching-to-point movements
      during motor practice and at motor retention. Index finger abductions and arm
      reaching movements increased M1 excitability. Cerebellar cTBS decreased the motor
      evoked potential (MEP) facilitation induced by index finger movements, but
      increased the MEP facilitation after reaching-to-grasp and reaching-to-point
      movements. Cerebellar stimulation prevents motor retention for index finger
      abductions, reaching-to-grasp and reaching-to-point movements and degrades motor
      practice only for reaching-to-point movements. Cerebellar cTBS alters practice
      related changes in M1 excitability depending on how intensely the cerebellum
      contributes to the task. Changes in M1 excitability reflect mechanisms of
      homeostatic plasticity elicited by the interaction of an 'exogenous' (cTBS
      induced) and an 'endogenous' (motor practice-induced) plasticity-inducing
      protocol. 

PMID- 24303980
TI  - Placental maturity, hypertensive disorders of pregnancy and birth weight.
AB  - OBJECTIVES: To compare maturity of placentas from women with hypertensive
      disorders with those from normotensive pregnancies and to determine the
      relationship between placental maturity (PM) and the diagnosis of small-for
      gestational-age (SGA) in the newborns. MATERIALS AND METHODS: We examined
      placental stained specimens from women with normotensive pregnancies (n = 100),
      diagnosis of gestational hypertension (n = 38), mild (n = 10), or severe
      preeclampsia (n = 34) in an optical microscope. Placental Maturity Index (PMI)
      was calculated as the number of vasculo-syncytial membranes (VSM) in 1 mm(2)
      divided by VSM thickness (um). Hypermaturity was defined as >90th percentile of
      the PMI from placentas of normotensive pregnancies. Newborns were classified as
      SGA, adequate-for-gestational-age (AGA) or large-for-gestational-age (<10th, 10
      90th, and >90th percentile from weight for gestational age reference tables,
      respectively). RESULTS: PMI in preeclamptic women (taking together mild and
      severe preeclampsia, PMI = 43.4 +/- 1.6) was significantly higher than in
      normotensive women (PMI = 36 +/- 2, p = 0.045). Hypermaturity was more frequent
      (p < 0.05) in placentas from women with preeclampsia than in those from
      normotensive women only in preterm pregnancies (<37 weeks), but not in those at
      term (p = 0.41). The frequency of hypermaturity in placentas from women with
      gestational hypertension was not statistically different than in normotensive
      women. Hypermaturity was also more frequent in placentas from SGA (OR = 2.63, p <
      0.05) than in AGA newborns. CONCLUSION: The PMI was increased in preeclampsia,
      but not in gestational hypertension. Placental hypermaturity was also associated
      with the diagnosis of SGA in newborns. PM might have a role in the relationship
      between maternal factors and SGA.

PMID- 24303979
TI  - Role of miR-155 in the regulation of lymphocyte immune function and disease.
AB  - MicroRNAs (miRNAs) have emerged as critical regulators of gene expression within
      cells. One particular miRNA, miR-155, is highly expressed within lymphocytes
      (both B and T cells) and mediates a number of important roles. These include
      shaping the transcriptome of lymphoid cells that control diverse biological
      functions vital in adaptive immunity. The use of mice engineered to be deficient
      in miR-155, as well as the identification of endogenous targets of miR-155 in T
      cells by transcriptome-wide analysis, has helped to unravel the crucial role that
      this miRNA plays in fine tuning the regulation of lymphocyte subsets such as B
      cells, CD8(+) and CD4(+) T cells ranging from T helper type 1 (Th1), Th2, Th17
      and regulatory T cells. In this review, we summarize what we have learned about
      miR-155 in the regulation of lymphocyte responses at the cellular and molecular
      levels and in particular, we focus on the recent findings showing that miR-155
      shapes the balance between tolerance and immunity. 

PMID- 24303981
TI  - The relationship of attention-deficit hyperactivity disorder and autism spectrum
      disorder to adaptive skills in young children.
AB  - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) has been linked to
      deficits in socialization and communication, similar to those observed in
      children with ASD. In the present study, we examine the differences in
      developmental quotient and subscale scores between children with ASD and children
      with ADHD. METHODS: We compared the developmental scores in a sample of 2990
      children who presented to an early intervention program, who met criteria for
      ASD, inattentive ADHD, hyperactive/impulsive ADHD, combined ASD/ADHD, or are at
      risk for developmental disorders. RESULTS: The overall developmental quotient did
      not significantly differ between those in the ADHD inattentive and hyperactive
      subtype groups. Adaptive skills differed most greatly between the ASD groups and
      the ADHD/atypically-developing groups. CONCLUSION: The present study represents a
      first step towards understanding the relationship of ADHD to ASD in early
      childhood. Young children with ASD symptoms are more greatly impaired than those
      with symptoms of ADHD.

PMID- 24303982
TI  - Facile preparation of well-dispersed CeO2-ZnO composite hollow microspheres with
      enhanced catalytic activity for CO oxidation.
AB  - In this article, well-dispersed CeO2-ZnO composite hollow microspheres have been
      fabricated through a simple chemical reaction followed by annealing treatment.
      Amorphous zinc-cerium citrate hollow microspheres were first synthesized by
      dispersing zinc citrate hollow microspheres into cerium nitrate solution and then
      aging at room temperature for 1 h. By calcining the as-produced zinc-cerium
      citrate hollow microspheres at 500  degrees C for 2 h, CeO2-ZnO composite hollow
      microspheres with homogeneous composition distribution could be harvested for the
      first time. The resulting CeO2-ZnO composite hollow microspheres exhibit enhanced
      activity for CO oxidation compared with CeO2 and ZnO, which is due to well
      dispersed small CeO2 particles on the surface of ZnO hollow microspheres and
      strong interaction between CeO2 and ZnO. Moreover, when Au nanoparticles are
      deposited on the surface of the CeO2-ZnO composite hollow microspheres, the full
      CO conversion temperature of the as-produced 1.0 wt % Au-CeO2-ZnO composites
      reduces from 300 to 60  degrees C in comparison with CeO2-ZnO composites. The
      significantly improved catalytic activity may be ascribed to the strong
      synergistic interplay between Au nanoparticles and CeO2-ZnO composites. 

PMID- 24303983
TI  - A role for PPARalpha in the medial prefrontal cortex in formalin-evoked
      nociceptive responding in rats.
AB  - BACKGROUND AND PURPOSE: The nuclear hormone receptor, PPARalpha, and its
      endogenous ligands, are involved in pain modulation. PPARalpha is expressed in
      the medial prefrontal cortex (mPFC), a key brain region involved in both the
      cognitive-affective component of pain and in descending modulation of pain.
      However, the role of PPARalpha in the mPFC in pain responding has not been
      investigated. Here, we investigated the effects of pharmacological modulation of
      PPARalpha in the rat mPFC on formalin-evoked nociceptive behaviour and the impact
      of formalin-induced nociception on components of PPARalpha signalling in the
      mPFC. EXPERIMENTAL APPROACH: The effects of intra-mPFC microinjection of a
      PPARalpha agonist (GW7647) or a PPARalpha antagonist (GW6471) on formalin-evoked
      nociceptive behaviour in rats were studied. Quantitative real-time PCR and LC
      MS/MS were used to study the effects of intraplantar injection of formalin on
      PPARalpha mRNA expression and levels of endogenous ligands, respectively, in the
      mPFC. KEY RESULTS: Intra-mPFC administration of GW6471, but not GW7647, resulted
      in delayed onset of the early second phase of formalin-evoked nociceptive
      behaviour. Furthermore, formalin-evoked nociceptive behaviour was associated with
      significant reductions in mPFC levels of endogenous PPARalpha ligands (N
      palmitoylethanolamide and N-oleoylethanolamide) and a 70% reduction in PPARalpha
      mRNA but not protein expression. CONCLUSIONS AND IMPLICATIONS: These data suggest
      that endogenous ligands may act at PPARalpha in the mPFC to play a
      facilitatory/permissive role in second phase formalin-evoked nociceptive
      behaviour in rats. 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- 24303984
TI  - Association between insulin resistance and periodontitis in Korean adults.
AB  - OBJECTIVE: Recent studies have proposed an association between periodontitis and
      metabolic abnormalities. We investigated the association between insulin
      resistance and periodontitis among Korean adults. METHODS: A cross-sectional
      analysis was conducted using the Korea National Health and Nutrition Examination
      Survey 2008-2010. A total of 16,720 non-diabetic subjects over 18 years old were
      evaluated (7060 men and 9660 women). Periodontal status was assessed by the
      Community Periodontal Index. Insulin resistance was measured using the
      homeostasis model assessment of insulin resistance (HOMA-IR). Participants in the
      highest and lowest quartile of HOMA-IR were defined as insulin-resistant and
      insulin-sensitive respectively. RESULTS: The prevalence of periodontitis
      increased significantly with higher HOMA-IR quartiles in post-menopausal women (p
      for linear association = 0.019). Among post-menopausal women, participants in the
      highest quartile of HOMA-IR were significantly more likely to have periodontitis
      compared to those in the lowest quartile [adjusted odds ratio (OR), 1.47; 95%
      confidence interval (CI), 1.07-2.01]. Moreover, obese post-menopausal women
      showed an increased association between insulin resistance and periodontitis
      (adjusted OR, 1.92; 95% CI,1.29-2.87). However, this association was not found in
      men or pre-menopausal women. CONCLUSIONS: Our results suggest that insulin
      resistance may be associated with periodontitis, especially when combined with
      obesity, among post-menopausal women in Korea.

PMID- 24303985
TI  - Chiral Lewis acid catalyzed asymmetric cycloadditions of disubstituted ketenes
      for the synthesis of beta-lactones and delta-lactones.
AB  - Highly diastereo- and enantioselective [2 + 2]- and [4 + 2]-cycloadditions of
      disubstituted ketenes were realized by chiral Lewis acid catalysis. A series of
      arylalkylketenes underwent the reaction smoothly with isatins and beta,gamma
      unsaturated alpha-ketoesters, providing optically active beta-lactones and delta
      lactones with vicinal chiral centers in excellent yields (up to 99%) and
      enantioselectivities (up to 99% ee), as well as exclusively high
      diastereoselectivities under 0.2-2 mol % catalyst loading. 

PMID- 24303986
TI  - Polymorphisms in calpastatin and mu-calpain genes are associated with beef iron
      content.
AB  - The objective of this study was to assess the association of markers in the
      calpastatin and mu-calpain loci with iron in beef cattle muscle. The population
      consisted of 259 cross-bred steers from Beefmaster, Brangus, Bonsmara,
      Romosinuano, Hereford and Angus sires. Total iron and heme iron concentrations
      were measured. Markers in the calpastatin (referred to as CAST) and mu-calpain
      (referred to as CAPN4751) genes were used to assess their association with iron
      levels. The mean and standard error for iron and heme iron content in the
      population was 35.6 +/- 1.3 MUg and 27.1 +/- 1.4 MUg respectively. Significant
      associations (P < 0.01) of markers were observed for both iron and heme iron
      content. For CAST, animals with the CC genotype had higher levels of iron and
      heme iron in longissimus dorsi muscle. For CAPN4751, individuals with the TT
      genotype had higher concentrations of iron and heme iron than did animals with
      the CC and CT genotypes. Genotypes known to be associated with tougher meat were
      associated with higher levels of iron concentration. 

PMID- 24303988
TI  - Docking studies on DNA intercalators.
AB  - DNA is an important target for the treatment of multiple pathologies, most
      notably cancer. In particular, DNA intercalators have often been used as
      anticancer drugs. However, despite their relevance to drug discovery, only a few
      systematic computational studies were performed on DNA-intercalator complexes. In
      this work we have analyzed ligand binding sites preferences in 63 high resolution
      DNA-intercalator complexes available in the PDB and found that ligands bind
      preferentially between G and C and between the C and A base pairs (70% and 11%,
      respectively). Next, we examined the ability of AUTODOCK to accurately dock
      ligands into preformed intercalation sites. Following the optimization of the
      docking protocol, AUTODOCK was able to generate conformations with RMSD values
      <2.00 A with respect to crystal structures in ~80% of the cases while focusing on
      the preformed binding site (small grid box) or on the entire DNA structure (large
      grid box). In addition, a top ranked conformation with an RMSD < 2.00 A was
      identified in 75% and 60% of the cases using small and large docking boxes,
      respectively. Moreover, under the large docking box setting AUTODOCK was able to
      successfully distinguish between the intercalation site and the minor groove
      site. However, in all cases the crystal structures and poses tightly clustered
      around it had a lower score than the best scoring poses suggesting a potential
      scoring problem with AUTODOCK. A close examination of all cases where the top
      ranked pose had an RMSD value >2.00 A suggests that AUTODOCK may overemphasize
      the hydrogen bonding term. A decision tree was built to identify ligands which
      are likely to be accurately docked based on their characteristics. This analysis
      revealed that AUTODOCK performs best for intercalators characterized by a large
      number of aromatic rings, low flexibility, high molecular weight, and a small
      number of hydrogen bond acceptors. Finally, for canonical B-DNA structures (where
      preformed sites are unavailable), we demonstrated that intercalation sites could
      be formed by inserting an anthracene moiety between the (anticipated) site
      flanking base pairs and by relaxing the structure using either energy
      minimization or preferably molecular dynamics simulations. Such sites were
      suitable for the docking of different intercalators by AUTODOCK. 

PMID- 24303987
TI  - Hamstrings stiffness and landing biomechanics linked to anterior cruciate
      ligament loading.
AB  - CONTEXT: Greater hamstrings stiffness is associated with less anterior tibial
      translation during controlled perturbations. However, it is unclear how
      hamstrings stiffness influences anterior cruciate ligament (ACL) loading
      mechanisms during dynamic tasks. OBJECTIVE: To evaluate the influence of
      hamstrings stiffness on landing biomechanics related to ACL injury. DESIGN: Cross
      sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A
      total of 36 healthy, physically active volunteers (18 men, 18 women; age = 23 +/-
      3 years, height = 1.8 +/- 0.1 m, mass = 73.1 +/- 16.6 kg). INTERVENTION(S):
      Hamstrings stiffness was quantified via the damped oscillatory technique. Three
      dimensional lower extremity kinematics and kinetics were captured during a double
      legged jump-landing task via a 3-dimensional motion-capture system interfaced
      with a force plate. Landing biomechanics were compared between groups displaying
      high and low hamstrings stiffness via independent-samples t tests. MAIN OUTCOME
      MEASURE(S): Hamstrings stiffness was normalized to body mass (N/m.kg(-1)). Peak
      knee-flexion and -valgus angles, vertical and posterior ground reaction forces,
      anterior tibial shear force, internal knee-extension and -varus moments, and knee
      flexion angles at the instants of each peak kinetic variable were identified
      during the landing task. Forces were normalized to body weight, whereas moments
      were normalized to the product of weight and height. RESULTS: Internal knee-varus
      moment was 3.6 times smaller in the high-stiffness group (t22 = 2.221, P = .02).
      A trend in the data also indicated that peak anterior tibial shear force was 1.1
      times smaller in the high-stiffness group (t22 = 1.537, P = .07). The high
      stiffness group also demonstrated greater knee flexion at the instants of peak
      anterior tibial shear force and internal knee-extension and -varus moments (t22
      range = 1.729-2.224, P < .05). CONCLUSIONS: Greater hamstrings stiffness was
      associated with landing biomechanics consistent with less ACL loading and injury
      risk. Musculotendinous stiffness is a modifiable characteristic; thus exercises
      that enhance hamstrings stiffness may be important additions to ACL injury
      prevention programs.

PMID- 24303989
TI  - Spontaneous fistulization of infected walled-off pancreatic necrosis into the
      duodenum and colon.

PMID- 24303990
TI  - Intrahepatic interleukin-17+ T cells and FoxP3+ regulatory T cells cooperate to
      promote development and affect the prognosis of hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Recent studies have shown that imbalance between tumor
      infiltrating interleukin (IL)-17(+) T cells and regulatory T cells (Tregs) is an
      important regulator of progression in various cancers, but little is known
      regarding this imbalance in hepatocellular carcinoma (HCC). This study explored
      the role of imbalance between IL-17(+) T cells and Tregs in the
      immunopathogenesis of HCC in patients with chronic hepatitis B (CHB) infection.
      METHODS: Fifty-six of patient-matched tumors and peritumoral surgical specimens
      from 56 patient with HCC and 136 liver biopsies specimens from 46 patients with
      CHB, 37 with atypical hyperplasia (AH), and 53 with HCC were enrolled. The
      expressions of IL-17, FoxP3, CD4, and CD8 in liver tissue were measured by
      immunochemistry for the evaluation of liver-infiltrating lymphocytes. RESULTS:
      The density of liver infiltrated FoxP3(+) Tregs was increased in a stepwise
      manner from CHB to AH then HCC, while there was a decreasing trend for the
      density of IL-17(+) T cells and CD8(+) T cells. In surgical specimens of less
      differentiated HCC, the quantity of tumor-infiltrating FoxP3(+) Tregs was
      significantly lower and IL-17(+) T cells and CD8(+) T cells were significantly
      higher. Additionally, peritumoral IL-17(+) T cells were increased in poorly
      differentiated HCC. High intratumoral FoxP3(+) Tregs with high intratumoral IL
      17(+) T cells showed a significantly lower overall survival (OS) and disease-free
      survival (DFS) compared with other groups (OS, P = 0.033; DFS, P = 0.004). High
      intratumoral FoxP3(+) Tregs with high peritumoral IL-17(+) T cells showed a
      significantly lower survival rate compared with other groups (OS, P < 0.001 and
      DFS, P < 0.001). CONCLUSION: Our findings suggest that intrahepatic IL-17(+) T
      cells and FoxP3(+) Tregs may cooperate to promote the progression of HCC.

PMID- 24303991
TI  - Continuous flow atomic force microscopy imaging reveals fluidity and time
      dependent interactions of antimicrobial dendrimer with model lipid membranes.
AB  - In this paper, an amphiphilic peptide dendrimer with potential applications
      against multi-resistant bacteria such as Staphylococcus aureus was synthesized
      and studied on model cell membranes. The combination of quartz crystal
      microbalance and atomic force microscopy imaging during continuous flow allowed
      for in situ monitoring of the very initial interaction processes and membrane
      transformations on longer time scales. We used three different membrane
      compositions of low and high melting temperature phospholipids to vary the
      membrane properties from a single fluid phase to a pure gel phase, while crossing
      the phase coexistence boundaries at room temperature. The interaction mechanism
      of the dendrimer was found to be time-dependent and to vary remarkably with the
      fluidity and coexistence of liquid-solid phases in the membrane. Spherical
      micelle-like dendrimer-lipid aggregates were formed in the fluid-phase bilayer
      and led to partial solubilization of the membrane, while in gel-phase membranes,
      the dendrimers caused areas of local depressions followed by redeposition of
      flexible lipid patches. Domain coexistence led to a sequence of events initiated
      by the formation of a ribbon-like network and followed by membrane solubilization
      via spherical aggregates from the edges of bilayer patches. Our results show that
      the dendrimer molecules were able to destroy the membrane integrity through
      different mechanisms depending on the lipid phase and morphology and shed light
      on their antimicrobial activity. These findings could have an impact on the
      efficacy of the dendrimers since lipid membranes in certain bacteria have
      transition temperatures very close to the host body temperature. 

PMID- 24303992
TI  - The relevance of security: A latent domain of attachment relationships.
AB  - In the present study an adult attachment dimension, latent to the constructs of
      security, anxiety, and avoidance, was hypothesized, wherein security was expected
      to occupy the most relevant position. Furthermore, the reciprocal functioning of
      attachment constructs and their interactions with self-esteem were explored. Four
      hundreds and thirty-four Italian university students responded to two adult
      attachment questionnaires (Attachment Style Questionnaire and Adult Attachment
      Questionnaire) and to the Rosenberg Self-esteem scale. A Many-Facet Rasch
      Measurement modeling approach was adopted. The main results can be summarized as
      follows: (a) security, anxiety, and avoidance are nested under one latent
      attachment dimension; (b) security occupies the most prominent position on the
      dimension; (c) security is positively associated with a moderate level of
      attachment anxiety and negatively related to avoidance; and (d) a positive
      interaction between self-esteem and security, and a negative relation between
      self-esteem and anxiety, were detected. Theoretical, clinical, and empirical
      implications of the results are further discussed.

PMID- 24303993
TI  - Association between placental pathology and neonatal outcome in preeclampsia: a
      large cohort study.
AB  - OBJECTIVE: To study associations between placental histopathology and neonatal
      outcome in preeclampsia (PE). STUDY DESIGN: The cohort consisted of 544 singleton
      pregnancies complicated by PE and managed at Karolinska University Hospital,
      Stockholm, Sweden during 2000-2009. Evaluation of placental histopathology was
      made by one senior perinatal pathologist, blinded to outcome. Clinical outcome
      was obtained from prospectively collected medical registry data and medical
      records. Main outcome measures were intrauterine fetal death, smallness for
      gestational age, admission to neonatal unit, major neonatal morbidity (defined as
      presence of intraventricular hemorrhage >= grade 3, retinopathy of prematurity >=
      grade 3, necrotizing enterocolitis, cystic periventricular leucomalacia and/or
      severe bronchopulmonary dysplasia) and neonatal mortality. Logistic regression
      analyses including gestational age were performed. RESULTS: Abnormal placental
      weight, both low (adjusted odds ratio (OR) [95% confidence interval] 5.2 [1.1
      24], p = 0.03) and high (adjusted OR 1048 [21-51 663], p < 0.001) for gestational
      age, was associated with major neonatal morbidity in preterm infants. Accelerated
      villous maturation was less prevalent in intrauterine fetal death pregnancies
      (adjusted OR 0.18 [0.04-0.77], p = 0.02). Decidual arteriopathy increased the
      odds for admission to neonatal care (adjusted OR 2.7 [1.1-6.5], p = 0.03).
      Infarction involving >=5% of the placenta was associated with intrauterine fetal
      death and small for gestational age infants (adjusted OR's 75 [5.5-1011], p =
      0.001 and 3.2 [1.7-5.9], p < 0.001; respectively). No relations between
      histological variables and neonatal mortality could be found. CONCLUSION:
      Placental pathology in PE reflects adverse perinatal events and deviant placental
      weight predicts adverse neonatal outcome in preeclamptic women delivering
      preterm. Placental investigation without delay can contribute to neonatal risk
      assessment.

PMID- 24303994
TI  - Prevalence, severity and risk factors of asthma, rhinitis and eczema in a large
      group of Chinese schoolchildren.
AB  - BACKGROUND: There is a lack of information on the prevalence, severity and risk
      factors of asthma, rhinitis and eczema in Chinese children. OBJECTIVE: To
      establish baseline data for a major longitudinal study of factors affecting
      asthma, rhinitis and eczema in a large group of children from the industrialized
      city of Shijiazhuang, China. METHODS: We used the International Study of Asthma
      and Allergies in Childhood questionnaire and studied 10 338 children, ages 6-18,
      from Shijiazhuang. RESULTS: The prevalence of childhood asthma, rhinitis and
      eczema is 1.2%, 13.5% and 11.8%, respectively. Boys had higher prevalence of
      these conditions than girls and younger children had higher prevalence of asthma
      and eczema but lower prevalence of rhinitis than older children. Breastfed
      children had lower prevalence of asthma and rhinitis, but not eczema, than non
      breastfed children. Overweight children had higher prevalence of asthma and
      rhinitis than those who were not overweight. Children exposed to paternal smoking
      had higher prevalence of rhinitis and eczema than those not exposed; children
      exposed to pets had higher prevalence of asthma and rhinitis than those not
      exposed. CONCLUSIONS: The prevalence of asthma in this study group is low, but
      the prevalence of rhinitis is high, and could be considered a major public health
      problem. The prevalence of asthma, rhinitis and eczema is generally higher in
      boys and younger children generally have higher prevalence of asthma and eczema
      but lower prevalence of rhinitis. Exposure to pets is a risk factor for rhinitis,
      being overweight is a risk factor for asthma and rhinitis, and exposure to
      parental smoking is a risk factor for asthma, rhinitis and eczema in these
      children.

PMID- 24303995
TI  - Osteomyelitis caused by Aspergillus species: a review of 310 reported cases.
AB  - Aspergillus osteomyelitis is a rare infection. We reviewed 310 individual cases
      reported in the literature from 1936 to 2013. The median age of patients was 43
      years (range, 0-86 years), and 59% were males. Comorbidities associated with this
      infection included chronic granulomatous disease (19%), haematological
      malignancies (11%), transplantation (11%), diabetes (6%), pulmonary disease (4%),
      steroid therapy (4%), and human immunodeficiency virus infection (4%). Sites of
      infection included the spine (49%), base of the skull, paranasal sinuses and jaw
      (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). The most
      common infecting species were Aspergillus fumigatus (55%), Aspergillus flavus
      (12%), and Aspergillus nidulans (7%). Sixty-two per cent of the individual cases
      were treated with a combination of an antifungal regimen and surgery.
      Amphotericin B was the antifungal drug most commonly used, followed by
      itraconazole and voriconazole. Several combination or sequential therapies were
      also used experimentally. The overall crude mortality rate was 25%.

PMID- 24303996
TI  - Application of synthetic photostable retinoids induces novel limb and facial
      phenotypes during chick embryogenesis in vivo.
AB  - We have recently developed a range of synthetic retinoid analogues which include
      the compounds EC23 and EC19. They are stable on exposure to light and are
      predicted to be resistant to the normal metabolic processes involved in the
      inactivation of retinoids in vivo. Based on the position of the terminal
      carboxylic acid groups in the compounds we suggest that EC23 is a structural
      analogue of all-trans retinoic acid (ATRA), and EC19 is an analogue of 13-cis
      retinoic acid. Their effects on the differentiation of pluripotent stem cells has
      been previously described in vitro and are consistent with this hypothesis. We
      present herein the first description of the effects of these molecules in vivo.
      Retinoids were applied to the anterior limb buds of chicken embryos in ovo via
      ion-exchange beads. We found that retinoid EC23 produces effects on the wing
      digits similar to ATRA, but does so at two orders of magnitude lower
      concentration. When larger quantities of EC23 are applied, a novel phenotype is
      obtained involving production of multiple digit 1s on the anterior limb. This
      corresponds to differential effects of ATRA and EC23 on sonic hedgehog (shh)
      expression in the developing limb bud. With EC23 application we also find digit 1
      phenotypes similar to thumb duplications described in the clinical literature.
      EC23 and ATRA are shown to have effects on the entire proximal-distal axis of the
      limb, including hitherto undescribed effects on the scapula. This includes
      suppression of expression of the scapula marker Pax1. EC23 also produces effects
      similar to those of ATRA on the developing face, producing reductions of the
      upper beak at concentrations two orders of magnitude lower than ATRA. In
      contrast, EC19, which is structurally very similar to EC23, has novel, less
      severe effects on the face and rarely alters limb development. EC19 and ATRA are
      effective at similar concentrations. These results further demonstrate the
      ability of retinoids to influence embryonic development. Moreover, EC23
      represents a useful new tool to investigate developmental processes and probe the
      mechanisms underlying congenital abnormalities in vertebrates including man. 

PMID- 24303997
TI  - PACAP receptor pharmacology and agonist bias: analysis in primary neurons and
      glia from the trigeminal ganglia and transfected cells.
AB  - BACKGROUND AND PURPOSE: A major challenge in the development of new medicines
      targeting GPCRs is the ability to quantify drug action in physiologically
      relevant models. Primary cell models that closely resemble the clinically
      relevant in vivo site of drug action are important translational tools in drug
      development. However, pharmacological studies in these models are generally very
      limited due to the methodology used. EXPERIMENTAL APPROACH: We used a
      neuropeptide system to demonstrate the applicability of using highly sensitive
      signalling assays in primary cells. We quantified the action of pituitary
      adenylate cyclase-activating peptide (PACAP)-38, PACAP-27 and vasoactive
      intestinal polypeptide in primary cultures of neurons and glia derived from rat
      trigeminal ganglia (TG), comparing our observations to transfected cells. KEY
      RESULTS: PACAP-responsive receptors in rat trigeminal neurons, glia and
      transfected PAC1n receptors were pharmacologically distinct. PACAP-38, but not
      PACAP-27, activated ERK in glia, while both forms stimulated cellular cAMP
      production. PACAP(6-38) also displayed cell-type-dependent, agonist-specific,
      antagonism. CONCLUSIONS AND IMPLICATIONS: The complexity of PACAP pharmacology in
      the TG may help to direct, more effectively, the development of disease
      treatments targeting the PACAP receptor. We suggest that these methodologies are
      broadly applicable to other primary cell types of human or animal origin, and
      that our approach may allow more thorough characterization of ligand properties
      in physiologically relevant cell types.

PMID- 24303999
TI  - Comparison of two sampling and culture systems for detection of Salmonella
      enterica in the environment of a large animal hospital.
AB  - REASONS FOR PERFORMING STUDY: Nosocomial salmonellosis is an important problem in
      veterinary hospitals that treat horses and other large animals. Detection and
      mitigation of outbreaks and prevention of healthcare-associated infections often
      require detection of Salmonella enterica in the hospital environment. OBJECTIVES:
      To compare 2 previously published methods for detecting environmental
      contamination with S. enterica in a large animal veterinary teaching hospital.
      STUDY DESIGN: Hospital-based comparison of environmental sampling techniques.
      METHODS: A total of 100 pairs of environmental samples were collected from stalls
      used to house large animal cases (horses, cows or New World camelids) that were
      confirmed to be shedding S. enterica by faecal culture. Stalls were cleaned and
      disinfected prior to sampling, and the same areas within each stall were sampled
      for the paired samples. One method of detection used sterile, premoistened
      sponges that were cultured using thioglycolate enrichment before plating on XLT-4
      agar. The other method used electrostatic wipes that were cultured using buffered
      peptone water, tetrathionate and Rappaport-Vassiliadis R10 broths before plating
      on XLT-4 agar. RESULTS: Salmonella enterica was recovered from 14% of samples
      processed using the electrostatic wipe sampling and culture procedure, whereas S.
      enterica was recovered from only 4% of samples processed using the sponge
      sampling and culture procedure. There was test agreement for 85 pairs of culture
      negative samples and 3 pairs of culture-positive samples. However, the remaining
      12 pairs of samples with discordant results created significant disagreement
      between the 2 detection methods (P<0.01). CONCLUSIONS: Persistence of Salmonella
      in the environment of veterinary hospitals can occur even with rigorous cleaning
      and disinfection. Use of sensitive methods for detection of environmental
      contamination is critical when detecting and mitigating this problem in
      veterinary hospitals. These results suggest that the electrostatic wipe sampling
      and culture method was more sensitive than the sponge sampling and culture
      method.

PMID- 24304000
TI  - Antimicrobial effect of an ultrasonic levitation washer disinfector with silver
      electrolysis and ozone oxidation on methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has rapidly emerged as a cause
      of severe and intractable skin infection. At present, there are no effective
      topical treatments, and infection or colonization by MRSA of the skin raises
      serious medical problems. We developed an ultrasonic levitation washer that
      generates silver ions (Ag(+)) and ozone (O3) to clean and sterilize medical
      devices. We report the effect of ultrasonic levitation (levitation) with Ag(+)
      and O3 on MRSA in vitro and in vivo. Antimicrobial effect against six MRSA
      strains of all agr types was examined under three in vitro conditions; cells
      floating in a water tank, cells infiltrating-, and cells forming a biofilm on an
      atelocollagen membrane. In the in vivo studies, we assayed the number of MRSA
      organisms that survived treatment on murine skin ulcers and evaluated the ulcer
      size. Levitation with Ag(+) dramatically decreased the survival of MRSA floating
      in a water tank. Levitation with Ag(+) and O3 significantly decreased the
      viability of MRSA that had infiltrated or formed a biofilm on atelocollagen
      membranes regardless of the level of biofilm production. In vivo studies showed
      that the number of MRSA on murine skin ulcers was significantly decreased when 15
      min treatment was performed for 7 consecutive days and that the ulcer size was
      significantly decreased after the seventh treatment course. Levitation with Ag(+)
      and O3 may be a valuable tool for treating MRSA infestation of the skin and for
      accelerating wound healing.

PMID- 24303998
TI  - Synergizing vaccinations with therapeutics for measles eradication.
AB  - INTRODUCTION: The measles virus is a major human pathogen responsible for
      approximately 150,000 deaths annually. The disease is vaccine preventable and
      eradication of the virus is considered feasible, in principle. However, a herd
      immunity exceeding 95% is required to prevent sporadic viral outbreaks in a
      population. Declining disease prevalence, combined with public anxiety over the
      vaccination's safety, has led to increased vaccine refusal, especially in Europe.
      This has led to the resurgence of measles in some areas. AREAS COVERED: This
      article discusses whether synergizing effective measles therapeutics with the
      measles vaccination could contribute to finally eradicating measles. The authors
      identify key elements in a desirable drug profile and review current disease
      management strategies and the state of experimental inhibitor candidates. The
      authors also evaluate the risk associated with viral escape from inhibition, and
      consider the potential of measles therapeutics in the management of persistent
      central nervous system (CNS) viral infection. Finally, the authors contemplate
      the possible impact of therapeutics in controlling the threat imposed by closely
      related zoonotic pathogens of the same genus as measles. EXPERT OPINION:
      Efficacious therapeutics used for post-exposure prophylaxis of high-risk social
      contacts of confirmed index cases may aid measles eradication by closing herd
      immunity gaps; this is due to vaccine refusal or failure in populations with
      overall good vaccination coverage. The envisioned primarily prophylactic
      application of measles therapeutics to a predominantly pediatric and/or
      adolescent population, dictates the drug profile. It also has to be safe and
      efficacious, orally available, shelf-stable at ambient temperature and amenable
      to cost-effective manufacturing.

PMID- 24304001
TI  - The road toward fully transparent medical records.

PMID- 24304002
TI  - Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B.
AB  - BACKGROUND: Prophylactic factor replacement in patients with hemophilia B
      improves outcomes but requires frequent injections. A recombinant factor IX Fc
      fusion protein (rFIXFc) with a prolonged half-life was developed to reduce the
      frequency of injections required. METHODS: We conducted a phase 3, nonrandomized,
      open-label study of the safety, efficacy, and pharmacokinetics of rFIXFc for
      prophylaxis, treatment of bleeding, and perioperative hemostasis in 123
      previously treated male patients. All participants were 12 years of age or older
      and had severe hemophilia B (endogenous factor IX level of <=2 IU per deciliter,
      or <=2% of normal levels). The study included four treatment groups: group 1
      received weekly dose-adjusted prophylaxis (50 IU of rFIXFc per kilogram of body
      weight to start), group 2 received interval-adjusted prophylaxis (100 IU per
      kilogram every 10 days to start), group 3 received treatment as needed for
      bleeding episodes (20 to 100 IU per kilogram), and group 4 received treatment in
      the perioperative period. A subgroup of group 1 underwent comparative sequential
      pharmacokinetic assessments of recombinant factor IX and rFIXFc. The primary
      efficacy end point was the annualized bleeding rate, and safety end points
      included the development of inhibitors and adverse events. RESULTS: As compared
      with recombinant factor IX, rFIXFc exhibited a prolonged terminal half-life (82.1
      hours) (P<0.001). The median annualized bleeding rates in groups 1, 2, and 3 were
      3.0, 1.4, and 17.7, respectively. In group 2, 53.8% of participants had dosing
      intervals of 14 days or more during the last 3 months of the study. In groups 1,
      2 and 3, 90.4% of bleeding episodes resolved after one injection. Hemostasis was
      rated as excellent or good during all major surgeries. No inhibitors were
      detected in any participants receiving rFIXFc; in groups 1, 2, and 3, 73.9% of
      participants had at least one adverse event, and serious adverse events occurred
      in 10.9% of participants. These events were mostly consistent with those expected
      in the general population of patients with hemophilia. CONCLUSIONS: Prophylactic
      rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding
      rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov
      number, NCT01027364.).

PMID- 24304003
TI  - Mechanisms underlying the basal forebrain enhancement of top-down and bottom-up
      attention.
AB  - Both attentional signals from frontal cortex and neuromodulatory signals from
      basal forebrain (BF) have been shown to influence information processing in the
      primary visual cortex (V1). These two systems exert complementary effects on
      their targets, including increasing firing rates and decreasing interneuronal
      correlations. Interestingly, experimental research suggests that the cholinergic
      system is important for increasing V1's sensitivity to both sensory and
      attentional information. To see how the BF and top-down attention act together to
      modulate sensory input, we developed a spiking neural network model of V1 and
      thalamus that incorporated cholinergic neuromodulation and top-down attention. In
      our model, activation of the BF had a broad effect that decreases the efficacy of
      top-down projections and increased the reliance of bottom-up sensory input. In
      contrast, we demonstrated how local release of acetylcholine in the visual
      cortex, which was triggered through top-down gluatmatergic projections, could
      enhance top-down attention with high spatial specificity. Our model matched
      experimental data showing that the BF and top-down attention decrease
      interneuronal correlations and increase between-trial reliability. We found that
      decreases in correlations were primarily between excitatory-inhibitory pairs
      rather than excitatory-excitatory pairs and suggest that excitatory-inhibitory
      decorrelation is necessary for maintaining low levels of excitatory-excitatory
      correlations. Increased inhibitory drive via release of acetylcholine in V1 may
      then act as a buffer, absorbing increases in excitatory-excitatory correlations
      that occur with attention and BF stimulation. These findings will lead to a
      better understanding of the mechanisms underyling the BF's interactions with
      attention signals and influences on correlations. 

PMID- 24304004
TI  - A well-defined silica-supported tungsten oxo alkylidene is a highly active alkene
      metathesis catalyst.
AB  - Grafting (ArO)2W(?O)(?CHtBu) (ArO = 2,6-mesitylphenoxide) on partially
      dehydroxylated silica forms mostly [(=SiO)W(?O)(?CHtBu)(OAr)] along with minor
      amounts of [(=SiO)W(?O)(CH2tBu)(OAr)2] (20%), both fully characterized by
      elemental analysis and IR and NMR spectroscopies. The well-defined oxo alkylidene
      surface complex [(=SiO)W(?O)(?CHtBu)OAr] is among the most active heterogeneous
      metathesis catalysts reported to date in the self-metathesis of cis-4-nonene and
      ethyl oleate, in sharp contrast to the classical heterogeneous catalysts based on
      WO3/SiO2. 

PMID- 24304005
TI  - Climate change impact and adaptation assessment on food consumption utilizing a
      new scenario framework.
AB  - We assessed the impacts of climate change and agricultural autonomous adaptation
      measures (changes in crop variety and planting dates) on food consumption and
      risk of hunger considering uncertainties in socioeconomic and climate conditions
      by using a new scenario framework. We combined a global computable general
      equilibrium model and a crop model (M-GAEZ), and estimated the impacts through
      2050 based on future assumptions of socioeconomic and climate conditions. We used
      three Shared Socioeconomic Pathways as future population and gross domestic
      products, four Representative Concentration Pathways as a greenhouse gas
      emissions constraint, and eight General Circulation Models to estimate climate
      conditions. We found that (i) the adaptation measures are expected to
      significantly lower the risk of hunger resulting from climate change under
      various socioeconomic and climate conditions. (ii) population and economic
      development had a greater impact than climate conditions for risk of hunger at
      least throughout 2050, but climate change was projected to have notable impacts,
      even in the strong emission mitigation scenarios. (iii) The impact on hunger risk
      varied across regions because levels of calorie intake, climate change impacts
      and land scarcity varied by region. 

PMID- 24304006
TI  - Importance of off-cycle species in the acid-catalyzed aza-Piancatelli
      rearrangement.
AB  - The observed rate of reaction in the dysprosium triflate catalyzed aza
      Piancatelli rearrangement is controlled by a key off-cycle binding between
      aniline and catalyst. Deconvoluting the role of these ancillary species greatly
      broadens our understanding of factors affecting the productive catalytic pathway.
      We demonstrate that the rate of reaction is controlled by initial competitive
      binding between the furylcarbinol and nitrogen nucleophile using either a
      Bronsted or Lewis acid catalyst and that the resulting rearrangement proceeds
      without involving the Bronsted and Lewis acid catalyst. This shows conclusively
      that the rate-controlling step and selectivity of reaction are decoupled. 

PMID- 24304007
TI  - The antagonism of aluminum against fluoride-induced oxidative stress and c-Fos
      overexpression in rat testes.
AB  - Sodium fluoride (NaF) has been found to interfere with the reproductive system of
      animals. However, the cellular mechanisms underlying the reproductive toxicity of
      fluoride are unclear. The present study aims to define a possible mechanism of
      NaF-induced reproductive toxicity with respect to mineral, oxidative stress and c
      Fos expression and the role of aluminum (Al) in intervening the toxic effect of
      NaF on rat testes. Fifty-six male Wistar rats were treated with normal saline,
      1.0, 2.0, and 3.0 mg NaF/kg body weight (bw)/day, and each NaF concentration plus
      Al ion (0.1 mg Al(3+)/kg bw/day). After 90 days, no significant changes in the
      contents of Fe and Cu were observed in any of the NaF-treated groups compared
      with those of the control group. There were, however, significant decreases in
      the contents of Ca in the 1.0 mg NaF group, Zn in all NaF-treated groups and Mg
      in the 3.0 mg NaF group. The levels of malondialdehyde (MDA) in the 1.0 mg NaF
      group and hydrogen peroxide (H2O2) in the 2.0 mg NaF group significantly
      increased, whereas the activity of nitric oxide synthase (NOS) significantly
      decreased in the 1.0 mg NaF group. Meanwhile, the protein expression of c-Fos
      increased significantly in the 1.0 and 2.0 mg NaF groups compared with the
      control group. Conversely, these changes were partially attenuated in rats
      simultaneously administered Al. The present study suggested that NaF could
      decrease the contents of Ca, Fe and Mg and enhance oxidative stress leading to c
      Fos overexpression, and some deleterious effects were more prominent at lower NaF
      intake. Furthermore, Al within the research concentration could minimize
      reproductive toxicity caused by fluoride.

PMID- 24304008
TI  - Prediction of individual compounds forming activity cliffs using emerging
      chemical patterns.
AB  - Activity cliffs are formed by structurally similar or analogous compounds having
      large potency differences. In medicinal chemistry, pairs or groups of compounds
      forming activity cliffs are of interest for structure-activity relationship (SAR)
      analysis and compound optimization. Thus far, activity cliff assessment has
      mostly been descriptive, i.e., compound data sets and activity landscape
      representations have been searched for activity cliffs in the context of SAR
      analysis. Only recently, first attempts have also been made to depart from
      descriptive analysis and predict activity cliffs. This has been done by building
      computational models that distinguish compound pairs forming activity cliffs from
      non-cliff pairs. However, it is principally more challenging to predict single
      compounds that participate in activity cliffs. Here, we show that individual
      compounds having high or low potency can be accurately predicted to form activity
      cliffs on the basis of emerging chemical patterns. 

PMID- 24304009
TI  - Self-cleaning membrane to extend the lifetime of an implanted glucose biosensor.
AB  - The lifetime and efficacy of a subcutaneously implanted glucose biosensor could
      be greatly improved by a self-cleaning membrane capable of periodic physical
      removal of adhered cells associated with the foreign body reaction. Previously,
      we reported a thermoresponsive double network nanocomposite (DNNC) membrane
      composed of poly(N-isopropylacrylamide) (PNIPAAm) and embedded polysiloxane
      nanoparticles. When the membrane was thermally cycled above and below its volume
      phase transition temperature (VPTT, ~33-35  degrees C), the associated deswelling
      and reswelling, respectively, led to in vitro cell release. Herein, this membrane
      design was tailored to meet the specific demands of a subcutaneously implanted
      glucose biosensor, and critical functional properties were assessed. First, N
      vinylpyrrolidone (NVP) comonomer increased the VPTT to ~38  degrees C so that the
      membrane would be swollen and thus more permeable to glucose in the "off-state"
      (i.e., no heating) while residing in the subcutaneous tissue (~35  degrees C).
      Second, glucose diffusion kinetics though the DNNC membrane was experimentally
      measured in its deswollen and reswollen states. A cylindrical DNNC membrane with
      dimensions considered suitable for implantation (1.5 * 5 mm, diameter * length)
      was used to model the glucose diffusion lag time. In addition, the DNNC cylinder
      was used to observe dimensional changes associated with deswelling and
      reswelling. Noncytotoxicity was confirmed and self-cleaning was assessed in vitro
      in terms of thermally driven cell release to confirm the potential of the DNNC
      membrane to control biofouling.

PMID- 24304010
TI  - Replicated association of single-nucleotide marker on chromosome 6 with bovine
      yearling weight using a mixed model analysis.

PMID- 24304011
TI  - Progression of attachment loss is strongly associated with presence of the JP2
      genotype of Aggregatibacter actinomycetemcomitans: a prospective cohort study of
      a young adolescent population.
AB  - AIM: To assess the progression of attachment loss (AL) during a 2-year period
      according to the presence of JP2 and non-JP2 genotypes of Aggregatibacter
      actinomycetemcomitans in a Ghanaian adolescent population. METHODS: A total of
      500 adolescents (mean age 13.2 years, SD +/- 1.5) were enrolled in the study.
      After 2 years, 397 (79.4%) returned for a periodontal re-examination, including
      the measurement of AL. The carrier status of the JP2 and non-JP2 genotypes of A.
      actinomycetemcomitans was evaluated in a baseline examination 2 years earlier.
      RESULTS: Individuals who carried the JP2 genotype of A. actinomycetemcomitans had
      a significantly increased risk [relative risk (RR) = 7.3] of developing AL >= 3
      mm. The mean AL at the follow-up and the mean 2-year progression of AL were
      significantly higher in the JP2 genotype-positive group (n = 38) compared with
      the group positive for the non-JP2 genotypes of A. actinomycetemcomitans (n =
      169), and the group of A. actinomycetemcomitans-negative individuals (n = 190).
      The JP2 genotype was strongly associated with the progression of AL >= 3 mm (OR =
      14.3). The non-JP2 genotypes of A. actinomycetemcomitans were also, however, less
      pronounced, associated with the progression of AL >= 3 mm (OR = 3.4). CONCLUSION:
      The JP2 genotype of A. actinomycetemcomitans is strongly associated with the
      progression of AL.

PMID- 24304012
TI  - Cytogenetics of prostate cancer.

PMID- 24304013
TI  - Reduction of nitric oxide with L-/NG-monomethyl arginine in interleukin-2 and
      anti-CD3 monoclonal antibody combination therapy.
AB  - We evaluated nitric oxide induction in antitumor therapy consisting of anti-CD3
      monoclonal antibody (anti-CD3) and interleukin-2 (IL-2), then determined the
      effect of nitric oxide reduction with L-N(G)-monomethyl arginine (LNMA) on the
      therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK-resistant
      murine fibrosarcoma cell line), and 145-2C11 (hamster anti-murine-CD3 mAb) were
      utilized in an experimental hepatic metastasis model developed by injecting a
      tumor cell suspension into the spleen of mice. A marked increase in serum NO2 (-)
      + NO1 was observed at 19 hours after anti-CD3 (10 MU, IV) and additional IL-2
      administrations (40 * 10(1) U, twice, If) induced a further increase. The NO2, +
      NO3- elevation in spot urine in the combination therapy was not suppressed with
      LNMA at a dose of 100 MUg/h but was significantly lowered at 300 MUg/h. The
      efficacy of the anti-CD3 + IL-2 therapy was not diminished by LNMA administration
      either at 100 MUg/h or at 300 MUg/h.

PMID- 24304014
TI  - Immunohistochemical study of TILs in renal cell carcinoma.

PMID- 24304015
TI  - Application of cytokine drug delivery systems to the immunotherapy of renal cell
      carcinoma in mice.
AB  - We have investigated the antitumor effects of human lymphoblastoid interferon
      (HLBI) mini-pellets, interleukin-2 (IL-2) entrapped in liposome (IL-2 liposome)
      and an immune complex of IL-2 and monoclonal antibody against IL-2 (IC-1). The
      HLBI mini-pellets were administered to nude mice bearing a human renal cancer
      cell line (KU-2). HLBI levels remained detectable both in the tumor tissue and
      the serum up to 10 days after peritumor injection. The HLBI mini-pellet
      significantly suppressed tumor growth by peritumor administration. The antitumor
      effect of IL-2 liposome on Renca, a murine renal cancer, resulted in the
      inhibition of tumor growth. An accumulation of Lyt-2(-) and L3T4 lymphocytes was
      seen in the tumor tissue which was treated with IL-2 liposomes. The IC-1 was
      prepared by mixing IL-2 and anti-IL-2 monoclonal antibody at a molar ratio of 2:
      1. Plasma IL-2 levels were sustained longer in mice given the IC-1 than in mice
      given IL-2 alone. The IC-1 complex exerted a more significant antitumor effect by
      local administration in Renca-bearing mice than the administration of IL-2 alone.
      We speculated that these effects were a result of sustained tumor IL-2 levels due
      to the increase in molecular weight. The results we obtained indicate that the
      cytokine drug delivery system has a long-acting cytotoxicity by administration to
      the tumor sites through efficient stimulation of the local immune response, and
      thus provides a useful tool for treatment of renal cell carcinoma. 

PMID- 24304016
TI  - New system to be implicated into the present interleukin-2 augmentation of
      cytotoxic-T lymphocytes.

PMID- 24304017
TI  - Immunohistochemical study of the proliferating ability and malignant potential of
      transitional cell carcinoma in the human urinary bladder.
AB  - Actively dividing cells produce a number of proteins that may serve as useful
      antigenic markers in immunological studies of cellular proliferation and
      malignant potential. We investigated the expression of PCNA, p53 and c-a erbB-2
      proteins in transitional cell carcinoma of human urinary bladder using an
      immunohistochemical method, and compared the results with the histologic grades
      and stages. Immunohistochemical studies on these proteins using monoclonal or
      polyclonal antibodies were performed with formalin-fixed paraffin sections of
      tumor tissue from 40 patients with bladder cancer. Generally, higher-grade and
      higher-stage tumors expressed PCNA and p53 and c-erbB-2 proteins with greater
      frequency than tumors of a lower grade or lower stage. These results suggest that
      the detection of each antigen might be useful in estimating the malignant
      potential of transitional cell carcinoma as an adjuvant study, because of its
      applicability to paraffin-embedded tissue sections and its simple, rapid
      technique. 

PMID- 24304018
TI  - Cytokine gene modification of bladder cancer cells for the establishment of
      bladder cancer vaccine.
AB  - A bladder tumor vaccine in mouse models was established by introducing
      interleukin-2 (IL-2) gene into mouse bladder cancer cells (MBT-2). Mice injected
      with non-modified MBT-2 cells did not reject subsequent challenge of MBT-2 cells.
      Mice injected with IL-2-gene-modified MBT-2 cells (MBT-2/IL-2) rejected
      subsequent challenge of unmodified MBT-2 cells but not 38C13 cells, which have
      the same genetic background but different antigenicity. According to these
      results, an injection of MBT-2/II.-2 can establish specific immunity against
      parental MBT-2 cells in mice, which is also demonstrated by cytotoxic T
      lymphocytes assay. Vaccinations with MBT-2/IL-2 cured 60% of bladder cancer which
      had been pre-established in mice. These results suggest that tumor cells
      genetically modified with IL-2 gene can act as a tumor vaccine which is expected
      to be a new method for immunotherapy of cancers. 

PMID- 24304019
TI  - Immunotherapy and gene therapy for genitourinary malignancies.

PMID- 24304020
TI  - Clinical innovations in urologic oncology.

PMID- 24304021
TI  - Treatment of advanced renal cell carcinoma with a combination of human
      lymphoblastoid interferon-alpha and cimetidine.
AB  - Human lymphoblastoid interferon (IFN)-alpha was administered intramuscularly at
      doses of 5 megaunits/day 5 to 7 days a week to 32 advanced renal cell carcinoma
      patients. To augment the antitumor effect of IFN, cimetidine was also
      administered orally in doses oi 800 mg/day. This combination therapy resulted in
      a complete response (CR) in 6 patients (19%), a partial response (PR) in 7 (22%),
      a stable disease (SD) in 11 (34%), and a progressive disease (PD) in 8 (25%). The
      response rate (CR+PR) was 41%. The pulmonary metastases were more receptive to
      IFN therapy than those at other sites. The median times to response were 2 months
      for PR, and 4.5 months for CR. The survival of the responder patients was
      significantly longer than the nonresponder patients. These results suggest that
      IFN-alpha and cimetidine combination therapy may be of use in the management of
      advanced renal cell carcinoma. 

PMID- 24304022
TI  - Intra-arterial infusion therapy following alteration of pelvic blood flow and
      concurrent radiation therapy for invasive bladder cancer.
AB  - Intra-arterial infusion therapy following alteration of pelvic blood flow and
      concurrent radiation therapy was performed in 13 patients with muscle invading
      bladder cancer (T2, 2; T3, 6; T4, 5). The internal iliac artery of the opposite
      side was embolized and the ipsilateral gluteal and obturator arteries were
      embolized by metallic coils. A catheter was placed in the ipsilateral internal
      iliac artery. CDDP was administered daily at a dose of 7-9 mg/body over 1 minute.
      Radiation was done by Microtron using 10 MV x-ray. Total dose was 4500-7060 cGy.
      Evaluation was done by cystoscopy, radiography and biopsy. Eight patients
      achieved complete response (CR) histologically. Others had partial response (PR).
      All CR patients had no recurrence. The observation period was between 3 and 29
      months, with a mean of 11 months. This treatment modality is effective for
      locally advanced bladder cancer. 

PMID- 24304023
TI  - Exact documentation of location and size of bladder tumor with a three
      dimensional mapping device.
AB  - BACKGROUND: Cystoscopy is one of the most important devices for diagnosing
      bladder tumor, but has a crucial shortcoming--the size of observed objects cannot
      be measured. This paper describes a new method to measure the position and size
      of a bladder tumor using a three-dimensional mapping device. METHODS: The three
      dimensional mapping device, which is connected to an endoscope prior to use, can
      precisely measure the size and show the position of a bladder tumor. It consists
      of several arms connected by an angle sensor mounted on the articular site. One
      end of the device is fixed to the table and the other end is connected to the eye
      piece of an endoscope. Weight balancers keep each arm in a well balanced
      position, so urologists can freely manipulate the endoscope. Data from the angle
      sensor is sent to a personal computer (PC), which computes data such as three
      dimensional coordination and diameter of a tumor. The diameter of a tumor is
      calculated by the PC according to the Pythagorean theorem. CONCLUSION: The
      position and size of a bladder tumor can be measured using our three-dimensional
      mapping device.

PMID- 24304024
TI  - Newly developed equipment and methods in the treatment of BPH: analysis of
      present status.
AB  - Benign prostatic hyperplasia (BPH) is the most common disease among the aged male
      population. A variety of symptoms are mainly caused by obstructive changes at the
      prostatic urethra. Transurethral resection (TURP) has been the gold standard of
      treatment, but new equipment and methods such as TUMT, HIFU, TUNA, and laser
      prostatectomy have been developed and are being tested for clinical application.
      Our experience with new equipment and methods show that their effectiveness has
      yet to be conclusively evaluated by objective parameters, while subjective
      improvements have been seen with less invasive treatments such as TUMT, HIFU and
      TUNA. Laser prostatectomy confirmed its advantages in hemostasis but comparison
      of each treatment is difficult because of different pathological changes created
      by different energy sources shown by MRI. Further studies are required to examine
      the new equipment and methods and for identification of the treatment of choice
      for BPH. 

PMID- 24304025
TI  - Clinical studies on advantages and safety of visual laser ablation for patients
      with benign prostatic hyperplasia.
AB  - Since 1992, we have been performing VLAP using a right-angle laser delivery
      system (Urolase) for BPH patients with significant underlying nonurological
      diseases such as diabetes mellitus, cardiovascular, pulmonary, and malignant
      diseases. Sufficient clinical results have been obtained without major
      complications during short-term and long-term observation. In this study, we
      discuss the clinical advantages and safety of VLAP, compared with TURP, through
      analysis of the clinical procedure for VLAP for patients treated with
      anticoagulant agents such as warfarin. In our study of 40 patients, 8 patients
      were treated with anticoagulants for cardiovascular disease. During the procedure
      and after the operation, no significant complications were encountered except for
      transient postoperative bleeding. The 8 patients who received simultaneous
      anticoagulant therapy also underwent TURP to draw a comparison. The time taken
      for the procedure and the volume of the blood loss were significantly reduced by
      VLAP. The hemostatic nature of YAG laser energy seems to result in a technical
      improvement over conventional I URP for patients undergoing anticoagulant
      therapy.

PMID- 24304026
TI  - Visual laser ablation of the prostate and transurethral resection of the prostate
      for benign prostatic hyperplasia.
AB  - For the past 50 years, transurethral resection of the prostate (TURP) has been
      the most common treatment for benign prostatic hyperplasia (BPH). The authors
      have conducted visual laser ablation of the prostate (VLAP) for BPH as a minimum
      invasive surgery. The results were compared with those of VLAP,
      VLAP+transurethral incision of the prostate (TUIP), and TURP as other treatments
      for BPH. In the VLAP group, 50 of 52 (96.2%), 36 of 40 (90.0%) and 31 of 36
      (86.1%) were categorized as having more than a Fair Response (FR) at 3, 6 and 12
      months, postoperatively. In the VLAP+TUIP group, 24 of 29 (82.8%), 19 of 22
      (86.4%) and 9 of 11 (81.8%) were classed as having more than a FR at 3, 6 and 1 2
      months, postoperatively. Forty-one of 42 (97.6%), 1 7 of 1 7 (100.0%) and 6 of 6
      (100.0%) patients reaction to TURP was more than FR in overall response at 3, 6
      and 12 months, postoperatively. The need for a blood transfusion, perforation of
      the prostate capsule and transit incontinence persisting for more than 1 month
      occurred in 1 of 45 (2.2%), 1 (2.2%) and 4 (8.9%) patients in the TURP group.
      Bladder neck contracture was seen in 4 of 52 (7.7%) in the VLAP group. Average
      postoperative catheter duration was shorter in the VLAP+TUIP (5.7 +/- 8.4 days)
      than in the VLAP group (10.3 +/- 10.4 days). Although TURP remains the standard
      treatment for BPH, VLAP results in less morbidity compared to TURP. VLAP with
      TUIP appears to lessen the risk of postoperative urinary retention and provide
      better results in longer follow-up studies. 

PMID- 24304027
TI  - Clinical evaluation of the results of open or transurethral surgery for prostate
      hypertrophy.
AB  - We evaluated the outcome of surgery for prostate hypertrophy through measurement
      of the urine flow rate and the Boyarsky symptom score. The study covered 108
      patients admitted to Showa University School of Medicine, Fujigaoka Hospital.
      Thirty-eight had been admitted for retropubic prostatectomy and the remaining 70
      patients for transurethral resection of the prostate. Their ages ranged from 48
      to 84 years, with an average age of 64.4 years. The urine flow rate was measured
      before and after prostatic operation using Dantec Urodyn 1000. The symptom scores
      were calculated according to the Boyarsky symptom score. The Student's t test was
      used for statistical analysis. Frequency (daytime, nighttime) was the most common
      preoperative symptom (97.2%, 96.3%), followed by impairment of stream (88.0%),
      and intermittency (78.7%). Frequently observed symptoms tended to raise the
      symptom scores. The period of admission, age and prostatic size did not correlate
      with the preoperative urine flow rate and symptom score. Significant improvements
      in the urine flow rate occurred after the operation. Frequency (daytime,
      nighttime) was the most common postoperative symptom (82.7%, 81.1%), followed by
      urgency (37.0%), then terminal dribbling (32.2%). Of 39 patients who were
      evaluated by symptom score and urine flow simultaneously, 6 patients (15.1%)
      failed to show improvement in 1 of the 2 evaluations, while 9 (23.1%) patients
      failed to show improvement in either. The irritative symptoms (frequency,
      urgency) tended not to show significant postoperative improvement. 

PMID- 24304028
TI  - Role of medical approach in the management of stone disease.
AB  - In the management of stone disease, the medical approach concerned with the
      prevention of stone recurrence is equally as important as the surgical removal of
      stones. The application of medical approach requires an understanding of the
      pathophysiology of stone formation. A wide variety of physiological or
      environmental disturbances have been identified in stone-forming patients. They
      include hypercalciuria, hypocitraturia, undue urinary acidity and
      hyperuricosuria. Reliable diagnostic protocols have been developed which are
      based on the presence of above derangements. The prophylactic treatment programs
      are directed at the correction or amelioration of underlying environmental
      disturbances. Conservative measures include a high fluid intake, dietary sodium
      and oxalate restriction, dietary calcium restriction (in absorptive
      hypercalciuria and primary hyperparathyroidism), and moderate animal protein
      restriction. Specific medical treatments chosen for discussion are thiazide, slow
      release neutral potassium phosphate, potassium citrate and potassium magnesium
      citrate. 

PMID- 24304029
TI  - Effect of sodium pentosan polysulfate and citrate on urinary stone formation in
      hyperoxaluric rats.

PMID- 24304030
TI  - Production of heparan sulfate in the process of calcium oxalate microlith
      formation.
AB  - To evaluate the interaction in the renal tubules between calcium oxalate
      microliths and glycosaminoglycans, especially heparan sulfate, we planned an
      experimentally-induced calcium oxalate microlith-producing model in rats. We
      found by immunofluorescence study and immunoelectron microscopy using the heparan
      sulfate antibody that heparan sulfate was produced in the renal tubular cells in
      the formation of calcium oxalate microliths and that heparan sulfate exists in
      the microliths. Heparan sulfate/crystal interaction might play a role as a
      nucleating agent and promote stone enlargement. 

PMID- 24304031
TI  - Experimental studies of adhesion and endocytosis of calcium oxalate crystals in
      renal tubular cells.
AB  - The present investigation was designed to study the interactions between Madin
      Darby canine kidney (MDCK) cells and calcium oxalate monohydrate (COM) crystals,
      the most abundant constituent of urinary crystals, and to clarify the
      significance of these crystal-cell interactions in stone pathogenesis. COM
      crystals adhered to the intact surface of MDCK cells by some biological
      mechanisms (biological adhesion) and, were then internalized into the cell
      (endocytosis). The microvilli of the cell appeared to play an important role in
      this process. In the kidneys of rats with experimentally induced stones, most COM
      crystals adhered to the tubular cells and some crystals were engulfed, via
      endocytosis. Thus, these crystal-cell interactions might be one of the earliest
      processes in the formation of kidney stones. Further elucidation of the mechanism
      and the regulatory factors of this process may provide new insight into stone
      pathogenesis. 

PMID- 24304032
TI  - Inhibitory potency of crystal matrix protein on the crystallization of calcium
      oxalate.
AB  - The presence of macromolecular substances is among the multiple factors that may
      influence the complex process of urinary stone formation. The aim of this study
      was to evaluate the inhibitory potency of crystal matrix protein (CMP).
      Purification of CMP consisted of calcium oxalate crystal formation, dissolution
      of crystals, electrodialysis and high-performance liquid chromatography (HPLC).
      The inhibitory potency of crystal aggregation was examined by the seed crystal
      method, the undiluted urine method, and the use of scanning electron microscopy
      (SEM). CMP showed the protein band of 31 kDa in SDS-PAGE. Anti-CMP polyclonal
      antibody and antihuman prothrombin antibody cross-reacted well with human
      prothrombin and CMP in Western blotting. CMP and human prothrombin had high
      inhibitory potency by the seed crystal method and undiluted urine method. Using
      SEM, we were able to observe the high inhibitory potency of human prothrombin and
      undiluted CMP on the aggregation of calcium oxalate crystals. 

PMID- 24304033
TI  - Women's perceptions of breastfeeding barriers in early postpartum period: a
      qualitative analysis nested in two randomized controlled trials.
AB  - OBJECTIVES: This study examined women's perceptions of early infant feeding
      experiences and identified early postpartum barriers to successful breastfeeding.
      SUBJECTS AND METHODS: We conducted semistructured exit interviews at 6 months
      postpartum with a subsample of participants (n=67) enrolled in two randomized
      controlled trials of breastfeeding promotion. Study arms included (1) routine pre
      and postnatal visits with an International Board Certified Lactation Consultant
      (IBCLC) (LC group), (2) electronically prompted guidance from prenatal care
      providers (EP group), (3) EP+LC combined, and (4) standard of care (control
      group). Interview transcripts were coded using grounded theory and analyzed in
      MAXqda. Code matrices were used to identify early postpartum breastfeeding
      barriers and were further examined in relation to treatment group using a mixed
      methods analysis. RESULTS: The majority of the participants reported experiencing
      at least one barrier to breastfeeding. Barriers to breastfeeding were more
      commonly reported in the early postpartum than late postpartum period. The most
      common barrier during the early postpartum period was the perception of
      inadequate milk supply ("lactational") (n=18), followed by problems with latch,
      medical problems that were perceived as precluding breastfeeding, and medical
      staff and hospital practices. Participants frequently reported that the IBCLCs
      assisted them in anticipating, managing, and overcoming these barriers.
      CONCLUSIONS: Our findings underscore the importance of integrating IBCLCs into
      routine pre- and postpartum care because they provide critical support that
      effectively addresses early postpartum barriers to breastfeeding.

PMID- 24304035
TI  - [Health and tradecorporations].
AB  - Health, determinants of health, health care, and health professionals in all
      countries are influenced by power of trade corporations. Singular interest of
      private corporate profits and businesses can affect health, such as the
      availability of tobacco, alcohol and others. Public health legislation and
      practice should consider the interests of the public and the importance of all
      health determinants.

PMID- 24304034
TI  - Employee perception of breastfeeding-friendly support and benefits of
      breastfeeding as a predictor of intention to use breast-pumping breaks after
      returning to work among employed mothers.
AB  - BACKGROUND: Although increasing numbers of large companies are complying with
      demands for a breastfeeding-friendly workplace by providing lactation rooms and
      breast-pumping breaks, the effectiveness for intention to use breast-pumping
      breaks to express breast milk among employed mothers is uncertain. To explore the
      impact of employees' perceived breastfeeding support from the workplace and the
      benefits of breastfeeding on a woman's intention to use breast-pumping breaks
      after returning to work, we conducted a survey at a female labor-intensive
      electronics manufacturer in Taiwan. SUBJECTS AND METHODS: A structured
      questionnaire survey was administered to 715 working mothers employed in an
      electronics manufacturing plant in Tainan Science Park in Southern Taiwan.
      Questionnaire content included female employee demographics, employment
      characteristics, and breastfeeding behavior after returning to work, as well as
      employees' perception of breastfeeding-friendly support and awareness of the
      benefits of breastfeeding when raising their most recently born child. RESULTS:
      Higher education (odds ratio [OR] 2.33), non-clean room worksite (OR 1.51),
      awareness of breast-pumping breaks (OR 4.70), encouragement by colleagues to use
      breast-pumping breaks (OR 1.76), and greater awareness of the benefits of
      breastfeeding (OR 1.08) were significant predictors of the use of breast-pumping
      breaks after returning to work, whereas the perception of inefficiency when using
      breast-pumping breaks reduced an employed mother's intention to use breast
      pumping breaks (OR 0.55). CONCLUSIONS: This study finds an association between an
      appreciation of the benefits provided by the employer and the likelihood of
      increased usage of breastfeeding breaks. Workplaces and employers can help
      employed mothers to understand the benefits of breastfeeding, which may increase
      the intention of the mother to take breast-pumping breaks after returning to
      work.

PMID- 24304036
TI  - [Perspectives of male contraception].
AB  - The principle of suppressive methods of male contraception is to repress the
      sperm production and its functions by hormonal, chemical, physical, immunological
      or other ways. Of hormonal methods, the most perspective seems to be the steroid
      blockade of spermatogenesis. In horizon of ten years, it might be expected that
      the first male hormonal contraception will be available in form of injections or
      implants, however the "male pill" will not become a reality in the near future.
      Blockade of calcium channels by means of pharmacological inhibitors seems to be
      another promising mechanism of sperm functions inhibition. Based on the results
      of research of last two decades, the method of "reversible vasectomy" might be
      accessible, too.

PMID- 24304037
TI  - [Deferred breast reconstruction - soul surgery?].
AB  - BACKGROUND: The loss or mutilation of a breast as a result of surgical treatment
      of neoplastic disease always represents a negative impact on a woman's psyche and
      negatively influences the quality of the woman's remaining life. The goal of our
      work was to implement deferred breast reconstruction into routine practice and
      the objectification of the influence of reconstruction on bodily integrity,
      quality of life, and the feeling of satisfaction in women. METHODS AND RESULTS:
      Women in remission from neoplastic disease after a radical mastectomy were
      indicated for breast reconstruction. Between January 2002 and December 2011
      deferred breast reconstruction was carried out 174 * on 163 women, with an
      average age of 49.2 and an age range of 29-67 years. The most frequently used
      reconstruction method was a simple gel augmentation of the breast or a Becker
      expander/implant - 51 (29.3%) and 37 (21.3%), or in combination with a lateral
      thoracodorsal flap (31; 17.8% and 47; 27%); reconstruction using a free DIEP flap
      was carried out 7 * (4%). Complications occurred in 19 operations (10.9%) with a
      dominance of inflammation and pericapsular fibrosis, in a subjective analysis,
      satisfaction with the results prevailed, along with an increased quality of life
      after reconstruction. CONCLUSION: A growing number of deferred breast
      reconstructions, women's satisfaction with the results, the positive influence of
      renewed bodily integrity on the feeling of life satisfaction and the quality of
      life have elevated breast reconstructions to a qualitatively higher level.

PMID- 24304038
TI  - [First experience with the personalised dependence degree assessment for the
      purposes of care allowance].
AB  - Personalised medicine in disability assessment was first implemented in 2010. It
      was not until two years later that the medical assessment paradigm used for
      dependence degree assessment for the purposes of care allowance was transformed.
      Since January 2012, there has been an aggregation of the 36 self-care and self
      sufficiency tasks into ten basic living needs , i.e. mobility, orientation,
      communication, food intake, putting on clothes and shoes, body hygiene, using the
      toilet, health care, personal activities, and household cleaning. Until the
      present moment, more than 150 thousand assessment cases have confirmed that
      personalised assessment of functional disabilities represents a significant
      improvement in the individualised approach to all clients of the social security
      system. The increase in the number of patients with confirmed dependence degrees
      III and IV has demonstrated that modern functional assessment is beneficial
      especially for patients with the most severe health impairments. Personalised
      medical assessment service represents the pursuit of an improved medical
      assessment of clients functional disabilities.

PMID- 24304039
TI  - Cryopreserved stem cell products containing dimethyl sulfoxide lead to activation
      of the coagulation system without any impact on engraftment.
AB  - BACKGROUND: Dimethyl sulfoxide (DMSO) is extensively used as a cryoprotectant in
      stem cell preservation. Little is known on direct hemostatic changes in
      recipients of hematopoietic stem cell transplantation (HSCT), immediately after
      DMSO administration. The objectives of the current study were to measure
      hemostatic changes during HSCT. STUDY DESIGN AND METHODS: In this prospective
      analysis, changes in plasma biomarkers, platelets (PLTs), or endothelial cells (D
      dimers, thrombin-antithrombin complex [TAT], microparticle activity as thrombin
      generation potential [MPA], whole blood aggregation, von Willebrand factor) were
      measured before and immediately after HSCT. Furthermore, associations with
      clinical complications were recorded. RESULTS: A total of 54 patients were
      included in the study. Mean MPA and TAT increased significantly immediately after
      HSCT, returning to baseline the day after the procedure (p<0.01). No significant
      differences in engraftment for neutrophils and PLTs were found in patients
      presenting a high increase of TAT or MPA compared with those presenting with a
      smaller increase. Patients with a high increase in TAT and MPA had received a
      greater number of total mononucleated cells (p<0.001) and higher transplant
      volumes (p=0.002). CONCLUSIONS: Infusion of stem cells containing DMSO reversibly
      activated coagulation, measured as thrombin generation. This finding was not
      associated with acute adverse events and did not influence engraftment. Further
      studies are needed to compare variable DMSO concentrations as well as DMSO-free
      products, to better address the influence of DMSO on hemostasis.

PMID- 24304040
TI  - Psychometric evaluation of the Dutch language version of the Child and Family
      Follow-up Survey.
AB  - AIM: The Child and Family Follow-up Survey (CFFS) is developed to monitor long
      term outcomes of children and youth with acquired brain injury (ABI). The aim of
      this study was to translate and adapt it into the Dutch language and to evaluate
      its reliability and validity. METHODS: The CFFS includes the Child and Adolescent
      Scale of Participation (CASP), the Child and Adolescent Factors Inventory (CAFI)
      and the Child and Adolescent Scale of Environment (CASE). The CFFS was translated
      into Dutch following international guidelines and adapted. The internal
      consistency, validity and test-retest reliability were examined among two groups
      of patients (n = 140 and n = 27) in the age of 5-22 years with ABI and their
      parents. RESULTS: The translation and adaptation resulted in the CFFS-DLV, Dutch
      language version. The CASP-DLV, CAFI-DLV and CASE-DLV had a good internal
      consistency, with Cronbach's alpha being 0.95, 0.89 and 0.83, respectively. There
      were statistically significant correlations among the three CFFS subscale scores.
      These scores were also significantly correlated with the total scores of the
      Pediatric Quality of Life Inventory (PedsQL, parent) and the Pediatric Stroke
      Outcome Measure, but not with the domain scores of the Children's Assessment of
      Participation and Enjoyment (CAPE). The test-retest reliability was good to
      moderate, with the intra-class correlation coefficients being 0.90 for the CASP
      DLV, 0.95 for the CAFI-DLV and 0.81 for the CASE-DLV. CONCLUSIONS: The CFFS-DLV,
      as translation and adaptation of the CFFS into Dutch, proved to be a promising
      instrument to measure long-term outcomes of children and youth with ABI. Further
      research is needed to examine its responsiveness to change and potential in other
      patient groups.

PMID- 24304041
TI  - Duodenal eosinophilia and early satiety in functional dyspepsia: confirmation of
      a positive association in an Australian cohort.
AB  - BACKGROUND AND AIM: Functional dyspepsia (FD), defined by unexplained pain or
      discomfort centered in the upper abdomen, is common. Diagnosis and treatment of
      FD based on the symptom-based Rome criteria remains challenging. Recently,
      eosinophilia in the duodenum has been implicated in the pathophysiology of FD in
      adults, specifically increased eosinophils in early satiety and postprandial
      distress, but the association remains controversial. The aim of this study was to
      characterize upper gastrointestinal (GI) tract pathology, specifically duodenal
      eosinophilia, in an Australian cohort of patients with FD. METHODS: Patients
      prospectively referred for an upper GI endoscopy (n = 55; mean age, 49.6 years;
      61.8% female) were stratified to FD cases (n = 33) and controls (n = 22) using
      Rome II criteria. All subjects completed a validated bowel symptom questionnaire.
      The eosinophil count per square millimeter in the duodenal bulb (D1) and second
      part (D2) was assessed and Helicobacter pylori status determined by gastric
      histology. Associations with clinical symptoms were assessed. RESULTS: Cases and
      controls were demographically similar. Duodenal eosinophilia was significantly
      increased in subjects experiencing early satiety (P = 0.01) and postprandial
      fullness (P = 0.001). This association was seen in D2 but not D1. Abdominal pain
      was associated with eosinophilia in both D1 (P = 0.02) and D2 (P = 0.005).
      Smoking was also associated with higher eosinophil counts in D2 (P = 0.007) and
      symptoms of early satiety (P = 0.02). CONCLUSIONS: Duodenal eosinophilia occurs
      in a subset of FD. The potential role of duodenal eosinophils in FD has
      implications for diagnosis and therapeutic trials.

PMID- 24304042
TI  - Toward improving the graphene-semiconductor composite photoactivity via the
      addition of metal ions as generic interfacial mediator.
AB  - We report a simple and general approach to improve the transfer efficiency of
      photogenerated charge carriers across the interface between graphene (GR) and
      semiconductor CdS by introducing a small amount of metal ions (Ca(2+), Cr(3+),
      Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+)) as "mediator" into their
      interfacial layer matrix, while the intimate interfacial contact between GR and
      CdS is maintained. This simple strategy can not only significantly improve the
      visible-light-driven photoactivity of GR-CdS semiconductor composites for
      targeting selective photoredox reaction, including aerobic oxidation of alcohol
      and anaerobic reduction of nitro compound, but also drive a balance between the
      positive effect of GR on retarding the recombination of electron-hole pairs
      photogenerated from semiconductor and the negative "shielding effect" of GR
      resulting from the high weight addition of GR. Our current work highlights that
      the significant issue on improving the photoactivity of GR-semiconductor
      composites via strengthening interfacial contact is not just a simple issue of
      tighter connection between GR and the semiconductor, but it is also the
      optimization of the atomic charge carrier transfer pathway across the interface
      between GR and the semiconductor. 

PMID- 24304043
TI  - Ambulatory blood pressure measurements in mid-pregnancy and development of
      hypertensive pregnancy disorders.
AB  - OBJECTIVE: To explore if blood pressure (BP) readings over 24 h is a useful
      addition to uterine artery Doppler to screen for hypertensive disorders. METHODS:
      In a prospective observational study, we invited nulliparous women with abnormal
      and normal uterine artery Doppler but normal BP at the time of their routine
      anomaly scan. BP was measured by the woman using automated apparatus at five
      specified time intervals over 24 h at 22-24 weeks. Pregnancy outcome was
      retrieved from delivery suite records, discharge summaries, and letters to
      general practitioners if necessary. Logistic regression was used to explore the
      contribution of uterine artery Doppler and BP measurements towards the
      development of pre-eclampsia. RESULTS: Data were available from 52 women with
      abnormal and 48 women with normal uterine artery Doppler. Thirteen women
      developed hypertension in pregnancy. Significant difference was found in the BP
      of women who did or did not develop hypertensive disorders. BP recordings showed
      the diurnal variation. Both uterine artery Doppler mean PI and BP showed
      significant correlation with future development of hypertension. CONCLUSIONS:
      Women can self-measure BP at home. BP readings show diurnal variation. There are
      significant differences in BP of women who do and do not develop hypertension
      later in the pregnancy. Use of home BP monitoring over 24 h of the day in mid
      pregnancy is unlikely to add to the use of uterine artery Doppler and a one-off
      BP reading for future development of hypertension in pregnancy.

PMID- 24304044
TI  - Support vector machines for drug discovery.
AB  - INTRODUCTION: Support vector machines (SVMs) are supervised machine learning
      algorithms for binary class label prediction and regression-based prediction of
      property values. In recent years, SVMs have become increasingly popular for drug
      discovery-relevant applications such as compound classification, the search for
      novel active compounds and property predictions. AREAS COVERED: The authors
      provide the readers with a brief introduction of SVM theory and discuss the
      kernel functions designed for drug discovery applications. The authors also
      review the different types of SVM applications in drug discovery, looking at
      particular case studies. Furthermore, the authors discuss the recent hybrid
      methods developed that incorporate SVM modeling in different ways. EXPERT
      OPINION: SVMs are currently among the best-performing approaches for chemical and
      biological property prediction and the computational identification of active
      compounds. It is anticipated that their use in drug discovery will further
      increase. Indeed, this will also include the development of SVM-based meta
      classifiers that combine different approaches and exploit their individual
      strengths and complementarity.

PMID- 24304045
TI  - Problematic severe asthma in children treated at high altitude: tapering the dose
      while improving control.
AB  - BACKGROUND: Multidisciplinary treatment at high altitude is a possible treatment
      option for problematic severe asthma (PSA) in children. This management can
      result in the tapering of inhaled corticosteroids. AIM: Our aim was to analyze
      the effect of multidisciplinary treatment at high altitude, notably the ability
      to taper corticosteroids. To get an insight into possible factors influencing
      tapering, we examined whether demographic variables, disease control and quality
      of life at treatment entrance could predict the tapering of corticosteroids.
      METHODS: This prospective open-phase cohort study analyzed the data of 43
      children aged 8-17 years referred to a specialized high altitude treatment
      centre. Lung function (FEV1, FEV1/VC), inflammation (FeNO), medication level,
      asthma control (ACT) and quality of life [PAQLQ(S)] were evaluated on admission
      and at discharge. RESULTS: Thirty-two (74%) children fulfilled PSA criteria.
      Three (7%) children used daily oral steroids. After 72 +/- 30 (mean +/- SD) days
      of treatment, the mean dosage of inhaled corticosteroids (ICS) could be
      significantly reduced from 1315 MUg +/- 666 budesonide equivalent to 1132 MUg +/-
      514. Oral steroid maintenance therapy could be stopped in all patients. FeNO,
      asthma control and quality of life improved (p < 0.001) from admission to
      discharge; FEV1 was in the normal range on both occasions. Apart from ICS levels
      at entrance, multiple regression analyses did not show any associated factor
      predicting the reduction of ICS dosage during treatment. CONCLUSION: The results
      indicate that high altitude treatment may be a treatment option for children with
      PSA, but it is not possible to predict ICS tapering off from health status
      variables at treatment entrance.

PMID- 24304046
TI  - Asthma control: importance of compliance and inhaler technique assessments.
AB  - OBJECTIVES: The available assessment tools to determine asthma control do not
      include components assessing factors that may directly affect control. Our aim
      was to evaluate the relationship between patient compliance, inhaler technique
      and the level of asthma control. METHODS: Scores from the Asthma Control Test,
      individual inhaler device checklists and a novel questionnaire on the patient's
      medication regimen were used to measure control, inhaler technique and
      compliance, respectively, in patients with asthma attending Sultan Qaboos
      University Hospital, Muscat, Oman during a 3-month period. RESULTS: All of the
      218 patients were receiving inhaled steroids, either in combination with long
      acting beta agonists (86.2%) or alone. Asthma control was good in 92 (42.2%)
      patients; with 38 males (50%) and 54 females (38%), respectively (p = 0.059).
      Compliance and inhaler technique were poor in 40.8% (89) and 18.3% (40) of the
      patients. 60% (36) of the patients with good and 59.4% (41) with partial
      compliance had good control while 83.1% (74) with poor compliance had poor
      control (p < 0.001). Of the 92 patients with good control, 86 (93.5%) exhibited
      good inhaler techniques. In contrast, 85% (34) of the patients with poor inhaler
      techniques demonstrated poor control (odds ratio [OR] = 5.3; 95% confidence
      interval [CI]: 2.05-14.8; p < 0.001). A total of 93.3% (56) with good and 89.9%
      (62) with partial compliance demonstrated good inhaler techniques (p < 0.001). In
      patients with good control, 35 (38%) exhibited both good inhaler techniques and
      compliance and 38 (41.3%) had a good technique and partial compliance.
      CONCLUSION: Patients with good inhaler techniques and compliance have better
      control of their asthma. Asthma control will remain suboptimal unless the reasons
      for this lack of control are identified, assessed and eliminated. We recommend
      that inhaler technique assessment and measurements of patient compliance with
      their prescribed treatments should be considered for inclusion in the current
      assessment tools.

PMID- 24304047
TI  - Complementary and alternative medicine use and asthma: relation to asthma
      severity and comorbid chronic disease.
AB  - OBJECTIVE: To determine (a) the prevalence of complementary and alternative
      medicine (CAM) use among people with asthma, and (b) if comorbid chronic disease
      and asthma severity are associated with CAM use. METHODS: This cross-sectional
      study utilized data from n = 15 276 adults who participated in the 2009
      Behavioral Risk Factor Surveillance System (BRFSS) and the 2009 Asthma Callback
      Survey (ACBS). Binary Logistic regression was used to determine if comorbid
      disease and asthma severity were associated with CAM use (yes/no). Model
      covariates were age, sex, income, and education. RESULTS: About 26% of
      respondents report using at least one form of CAM. The most frequently reported
      form of CAM use is breathing exercises (19.8%). The results indicate that neither
      comorbid cardiovascular disease, diabetes, nor stroke are related to CAM use, but
      individuals with more severe asthma symptoms were more likely to use CAM (OR =
      1.05, 95% CI 1.04, 1.05). CONCLUSIONS: CAM remedies most often reported by people
      with asthma (breathing techniques, vitamins) are unlikely to pose safety risks.
      Comorbid chronic disease does not motivate people with asthma to seek
      unconventional remedies. The increase in CAM use with asthma severity prompts
      questions about factors that might drive this behavior, such as
      untreated/inadequately treated disease, or medication side effects.

PMID- 24304048
TI  - Japanese adolescents' disclosure and information management with parents.
AB  - Adolescents' obligation to disclose and their actual disclosure about their
      activities to parents, justifications for nondisclosure, and strategies for
      information management were examined in different domains in 460 middle
      adolescents (M(age) = 16.6 years) from working and middle-class families in
      Japan. Adolescents felt most obligated to disclose prudential issues, but
      disclosed most about personal issues. Adolescents primarily justified
      nondisclosure with claims to personal choice and for prudential issues, concerns
      with parental disapproval. They rarely lied and mostly told parents if asked or
      avoided the issue. Findings revealed consistencies with prior work on disclosure
      with European and U.S. adolescents, as well as patterns specific to the Japanese
      cultural setting.

PMID- 24304049
TI  - Ultraviolet B irradiation increases the expression of inflammatory cytokines in
      cultured sebocytes.
AB  - Sebaceous gland hyperplasia and increased sebum secretion after irradiation of
      ultraviolet (UV)-B has been widely accepted. This study was performed to clarify
      expression of inflammatory cytokines after irradiating UV-B in cultured
      sebocytes. Reverse transcription polymerase chain reaction was performed to
      measure gene expression of inflammatory cytokines, including interleukin (IL)
      1beta, IL-6, IL-8 and tumor necrosis factor-alpha, in cultured sebocytes after
      exposure to 40 and 70 mJ/cm(2) UV-B. Protein expression of inflammatory cytokines
      and lipid production in cultured sebocytes after exposure to UV-B were measured
      using enzyme-linked immunoassay and lipid analysis kit. The expression of
      inflammatory cytokines, especially IL-1beta and IL-8, was significantly increased
      in cultured sebocytes after treatment with UV-B. Many more studies on the effect
      of UV-B on sebaceous glands should be performed to reveal the pathogenic
      mechanism of acne. 

PMID- 24304050
TI  - Assessing participant-centered outcomes to improve clinical research.

PMID- 24304051
TI  - Fertility treatments and multiple births in the United States.
AB  - BACKGROUND: The advent of fertility treatments has led to an increase in the rate
      of multiple births in the United States. However, the trends in and magnitude of
      the contribution of fertility treatments to the increase are uncertain. METHODS:
      We derived the rates of multiple births after natural conception from data on
      distributions of all births from 1962 through 1966 (before fertility treatments
      were available). Publicly available data on births from 1971 through 2011 were
      used to determine national multiple birth rates, and data on in vitro
      fertilization (IVF) from 1997 through 2011 were used to estimate the annual
      proportion of multiple births that were attributable to IVF and to non-IVF
      fertility treatments, after adjustment for maternal age. Trends in multiple
      births were examined starting from 1998, the year when clinical practice
      guidelines for IVF were developed with an aim toward reducing the incidence of
      multiple births. RESULTS: We estimated that by 2011, a total of 36% of twin
      births and 77% of triplet and higher-order births resulted from conception
      assisted by fertility treatments. The observed incidence of twin births increased
      by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order
      births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from
      1998 to 2011. This decrease coincided with a 70% reduction in the transfer of
      three or more embryos during IVF (P<0.001) and a 33% decrease in the proportion
      of triplet and higher-order births attributable to IVF (P<0.001). CONCLUSIONS:
      Over the past four decades, the increased use of fertility treatments in the
      United States has been associated with a substantial rise in the rate of multiple
      births. The rate of triplet and higher-order births has declined over the past
      decade in the context of a reduction in the transfer of three or more embryos
      during IVF. (Funded by the Centers for Disease Control and Prevention.).

PMID- 24304052
TI  - Global maternal, newborn, and child health--so near and yet so far.

PMID- 24304053
TI  - Mitochondrial dynamics--mitochondrial fission and fusion in human diseases.

PMID- 24304054
TI  - Images in clinical medicine. Evolution of a diabetic foot infection.

PMID- 24304055
TI  - Clinical problem-solving. A shocking development.

PMID- 24304056
TI  - Riociguat for pulmonary hypertension.

PMID- 24304057
TI  - Riociguat for pulmonary hypertension.

PMID- 24304058
TI  - Riociguat for pulmonary hypertension.

PMID- 24304059
TI  - Riociguat for pulmonary hypertension.

PMID- 24304060
TI  - Riociguat for pulmonary hypertension.

PMID- 24304061
TI  - Randomized clinical trials--removing obstacles.

PMID- 24304062
TI  - Randomized clinical trials--removing obstacles.

PMID- 24304063
TI  - Abusive prescribing of controlled substances.

PMID- 24304064
TI  - Images in clinical medicine. Spinal fracture and a widened interspinous gap.

PMID- 24304066
TI  - An interview with Mary Ann Liebert, publisher of Stem Cells and Development.

PMID- 24304068
TI  - An interview with Teruo Okano, PhD.

PMID- 24304067
TI  - National Institutes of Health Center for Regenerative Medicine: putting science
      into practice.
AB  - The field of regenerative medicine has been revolutionized by breakthroughs in
      stem cell biology, gene engineering, and whole-genome sequencing. These advances
      are not only scientific or medical but have also advanced how we conceptualize
      regenerative medicine. The progenitive research that proceeded as well as a
      substantial part of the funding that supported these discoveries were provided by
      the National Institutes of Health (NIH). Now, perhaps more than ever, the NIH has
      a vital role to play in the translation of science into clinical practice. The
      NIH is uniquely positioned to coordinate interactions between the different
      institutes and other arms of the government, as well as international
      organizations. Efforts of researchers in the United States both within and
      without the NIH are supported by a number of mechanisms, including specialized
      workshops, and the support of developing small-scale industry. Additionally, the
      NIH has stepped up to provide necessary infrastructure in areas of regenerative
      medicine where the medical need might be apparent but might be currently
      infeasible or unattractive to private-sector investment. This article will
      discuss these perhaps lesser-known activities of the NIH, which I believe have
      continued and will continue to contribute to the role of stem cell research in
      translating science into regenerative medicine.

PMID- 24304069
TI  - Regulation of cell-based therapies in Europe: current challenges and emerging
      issues.
AB  - Europe is ready to deploy its immense capital of knowledge into the development
      of effective cell-based therapies and delve into the global race for translating
      stem cell science into regenerative medicine. But what are the challenges and the
      emerging issues that lay ahead the realization of Europe's enormous potential in
      this field? Both researchers and industrial stakeholders tend to impute the slow
      pace of translation to specific suboptimal features of the regulatory environment
      in Europe. At the same time, a host of new issues are emerging as testified by a
      recent public controversy regarding the provision of unproven cell therapy in
      Italy. We will review this topic and suggest some solutions to foster the
      responsible development of innovative cell-based therapies in Europe.

PMID- 24304070
TI  - Regenerative medicine blueprint.
AB  - Regenerative medicine, a paragon of future healthcare, holds unprecedented
      potential in extending the reach of treatment modalities for individuals across
      diseases and lifespan. Emerging regenerative technologies, focused on structural
      repair and functional restoration, signal a radical transformation in medical and
      surgical practice. Regenerative medicine is poised to provide innovative
      solutions in addressing major unmet needs for patients, ranging from congenital
      disease and trauma to degenerative conditions. Realization of the regenerative
      model of care predicates a stringent interdisciplinary paradigm that will drive
      validated science into standardized clinical options. Designed as a catalyst in
      advancing rigorous new knowledge on disease causes and cures into informed
      delivery of quality care, the Mayo Clinic regenerative medicine blueprint offers
      a patient-centered, team-based strategy that optimizes the discovery-translation
      application roadmap for the express purpose of science-supported practice
      advancement.

PMID- 24304071
TI  - Somatic cell nuclear transfer in Oregon: expanding the pluripotent space and
      informing research ethics.
AB  - In May, Oregon Health and Science University (OHSU) announced the successful
      derivation, by the Mitalipov laboratory, of embryonic stem cells by somatic cell
      nuclear transfer. This experiment was recognized as a "formidable technical feat"
      and potentially a key step toward developing cell-based therapies. The OHSU
      report is also an example of how a scientific breakthrough can inform research
      ethics. This article suggests ways that nuclear transfer embryonic stem cell
      lines may contribute to research ethics by adding rigor to studies addressing
      pressing research questions important to the development of cell-based therapies.

PMID- 24304072
TI  - Fostering public cord blood banking and research in Canada.
AB  - In June 2013, Canadian Blood Services (CBS) established the National Public Cord
      Blood Bank (NPCBB) accessible to Canadian and international patients and
      researchers. The NPCBB promotes efforts that contribute to research and improved
      clinical care by making units not suitable for banking or transplantation
      available for research. In the context of the NPCBB of the CBS, this article will
      focus on the practical tools (e.g., consent protocols) developed to optimize
      umbilical cord blood (UCB) banking and research while enabling ethical provenance
      of UCB stem cells. The Canadian approach represents an ideal model for comparison
      as it is a country in which the national public bank (and other
      regional/provincial public banks) coexists with private companies.

PMID- 24304073
TI  - The Cell Therapy Catapult: growing a U.K. cell therapy industry generating health
      and wealth.
AB  - In a recent report on the regenerative medicine sector, the U.K. House of Lords
      made several recommendations to enable the United Kingdom to become a global
      leader in this important industry. Its recommendations in this regard were many
      and various, covering the regulatory system, clinical trials, manufacturing,
      funding, approval, and reimbursement. In its mission to tackle what it sees as
      three main types of barriers to the development of the cell therapy industry in
      the United Kingdom, the Cell Therapy Catapult is tackling many of these issues.
      Established as a center of excellence in the United Kingdom in 2012, the Cell
      Therapy Catapult is a research organization expected to grow to a team of around
      100 experts. Its core financing of L 70 million over the next 5 years is provided
      by the Technology Strategy Board, the United Kingdom's innovation agency, and
      with additional contract research income and access to collaborative funds, the
      Catapult expects to build up to annual revenues of around L 30 million. Along
      with its sister Catapult programs in other areas of the economy, the Cell Therapy
      Catapult was established after identification of the massive early-stage
      expertise the country has, as well as an acute market failure-the lack of
      expertise to translate early-stage cell therapy research into commercial success.
      In this article, in addition to showing our progress so far, we will discuss the
      hurdles the industry faces-grouped into business, manufacturing/supply chain
      issues, and clinical/regulatory issues-and what we are doing to help the United
      Kingdom leap over them.

PMID- 24304074
TI  - Stem cell research and therapies in Argentina: the legal and regulatory approach.
AB  - Argentina has a significant number of researchers in public and private
      institutions conducting research in regenerative medicine and stem cells. There
      is not specific legislation in this area; however, the National Ministry of
      Health has issued regulations under the scope of the Transplant Act and the
      Medicines Act. Alongside the groups doing research, it is possible to find
      professionals offering experimental stem cell therapies to patients. These
      professionals take refuge in the term "medical practice" and sell experimental
      treatment to patients with no guarantee of safety and security given that they
      were not tested in clinical research. These practices offered to patients in a
      scheme, apparently legal, are generating an important number of judicial actions
      requesting the payment of said treatments. The decisions of the courts ordering
      payment in most cases are generating a transfer of funds from patients, social
      welfare systems, and the state to medical centers offering stem cell experimental
      therapies. This article describes the current regulations as well as the course
      of action to solve the emerging problems of these new technologies at legislative
      level.

PMID- 24304075
TI  - The U.S. Food and Drug Administration should solidify the legal basis for its
      authority over reproductive cloning.
AB  - The promise and potential of stem cell research is apparent. However, ethical
      questions still linger. There is as yet no consensus in the U.S. Congress on how
      to address the issue of reproductive cloning and media confusion of this and the
      quite separate issue of therapeutic cloning inhibits therapeutic advance. This
      paper outlines the need for the FDA to undertake a deliberate process, with input
      from all stakeholders, to authoritatively establish its jurisdiction over human
      reproductive cloning so as to foster the life-saving potential of therapeutic
      cloning.

PMID- 24304076
TI  - The European Court of Justice's decision regarding the Brustle patent and its
      implications for the legality of stem cell research within the European Union.
AB  - In 2011 the European Court of Justice issued a decision regarding the
      patentability of technologies derived from human embryonic stem cells. The
      finding will have an impact on the framework of stem cell research within the
      European Union and its Member States and has already triggered several political
      initiatives regarding the funding of research with human embryonic stem cells on
      the European level as well as a renewed public debate. This article will take a
      short look at the case history and the findings of the court. It offers some
      critical comments regarding the findings' consistency with European and
      international regulations on intellectual property rights as well as some
      considerations on the possible impact of the case for other fields of law.

PMID- 24304077
TI  - The ethical and regulatory-compliant training and practice of regenerative
      surgery in the United States and abroad.
AB  - Regenerative surgery (RS) may be functionally defined as: the application of
      regenerative material and techniques such as live cells or cell-derived material
      with surgical methods to affect clinical therapy for disease or restore normal
      human function. A global review of RS as it relates to formal residency and
      fellowship medical education programs is provided in addition to the current
      state of post-graduate medical education. Due to the complex nature of starting
      materials (i.e. live cells or derived biologics), invariably ancillary staff
      versant in high complexity laboratory techniques will be required to support
      these novel clinical lines of service in the RS industry. Theoretical
      implications on both the development, training and credentialing of these unique
      professionals are preliminarily addressed. Although the current state of RS
      medical education has taken a predominantly conference and post-graduate approach
      across multiple surgical specialties, most new fields of surgery have developed
      under similar principles historically and should not be interpreted entirely as
      illegitimate or inappropriate.

PMID- 24304078
TI  - Stem cells: intellectual property issues in regenerative medicine.
AB  - The topic of stem cells for use in regenerative medicine, especially embryonic
      stem cells, inspires much debate, discussion, and outrage as it slices through
      the very core moral values of society. These social and moral issues have, in
      turn, resulted in government policies that have influenced the study of stem
      cells in regenerative medicine.

PMID- 24304080
TI  - Navigating the U.S. Food and Drug Administration's Regulatory Science initiative:
      an imperative for stem cell research and regenerative medicine advocates.

PMID- 24304079
TI  - The implementation of novel collaborative structures for the identification and
      resolution of barriers to pluripotent stem cell translation.
AB  - Increased global connectivity has catalyzed technological development in almost
      all industries, in part through the facilitation of novel collaborative
      structures. Notably, open innovation and crowd-sourcing-of expertise and/or
      funding-has tremendous potential to increase the efficiency with which biomedical
      ecosystems interact to deliver safe, efficacious and affordable therapies to
      patients. Consequently, such practices offer tremendous potential in advancing
      development of cellular therapies. In this vein, the CASMI Translational Stem
      Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing
      academically rigorous and commercially practicable solutions to a range of
      challenges in pluripotent stem cell translation. Critically, the CTSCC research
      agenda is defined through continuous consultation with its international funding
      and research partners. Herein, initial findings for all research focus areas are
      presented to inform global product development strategies, and to stimulate
      continued industry interaction around biomanufacturing, strategic partnerships,
      standards, regulation and intellectual property and clinical adoption.

PMID- 24304081
TI  - Commercialization and stem cell research: a review of emerging issues.
AB  - Stem cell researchers face pressure to develop therapies that will reach the
      clinic within a short period of time. Yet, this pressure may be unrealistic, as
      bringing stem cell innovations to the clinic will likely require significant time
      and financial investment. In a variety of biomedical fields, some evidence
      suggests that commercialization pressures and strategies may negatively impact
      research. These negative impacts may also be felt in the field of stem cell
      research, unless the challenges and issues are addressed in the design and
      implementation of commercialization policies. Further inquiry into the impact of
      commercialization on the field of stem cell research is required.

PMID- 24304082
TI  - Centre for Commercialization of Regenerative Medicine: moving forward with
      regenerative medicine commercialization in Canada.

PMID- 24304083
TI  - Value-engineered translation for regenerative medicine: meeting the needs of
      health systems.
AB  - Despite high expectations of economic returns, large investments in regenerative
      medicine technology have yet to materialize, partly due to a lack of proven
      business and investment models, regulatory hurdles, and a greater focus on cost
      effectiveness for reimbursement decisions by payors. Adoption of new economic
      modeling methods will better link investment decisions to value-based criteria of
      health systems.

PMID- 24304084
TI  - The next frontier: stem cells and the Center for the Advancement of Science in
      Space.
AB  - The Center for the Advancement of Science in Space (CASIS) manages the
      International Space Station U.S. National Laboratory, supporting space-based
      research that seeks to improve life on Earth. The National Laboratory is now open
      for use by the broad scientific community--and CASIS is the gateway to this
      powerful in-orbit research platform.

PMID- 24304085
TI  - Translation of amnion stem cells to the clinic.
AB  - Cellular therapy for liver disease has been available in the clinic for more than
      20 years, yet remarkably few patients receive this experimental therapy. Reasons
      for the small number of transplants performed are partially related to access to
      useful liver tissue and the difficulty with the isolation of viable cells. Stem
      cell sources of hepatocytes could theoretically relieve these obstacles to
      therapy if large numbers of functional hepatocytes could be generated and
      transplanted without risk of tumorigenicity. To date, there are no reports of
      stem cell sources with all of these characteristics, despite claims otherwise.
      Here we report the results of preclinical studies with appropriate animals models
      of metabolic liver disease and acute liver failure, and their correction by the
      transplantation of human amnion epithelial stem cells. The encouraging results of
      the preclinical studies have motivated the movement of isolation and banking of
      these cells to good manufacturing practice conditions so that the cells can be
      used in the clinic for transplantation of patients with liver disease.

PMID- 24304086
TI  - Background and future considerations for human cord blood hematopoietic cell
      transplantation, including economic concerns.
AB  - Cord blood (CB) has been used since 1988 as a source of hematopoietic stem cells
      (HSCs) and progenitor cells for hematopoietic cell transplantation (HCT) to treat
      patients with malignant and nonmalignant disorders. CB has both advantages and
      disadvantages when compared with other tissue sources of HSCs such as bone marrow
      and mobilized peripheral blood, which are also being used in the setting of HCT.
      This short review focuses on some historical information, as well as current
      efforts that are being assessed to enhance the efficacy of CB HCT. Also of
      importance are the costs of CB, and the feasibility and economics of using such
      to be identified, and newly confirmed improvements worldwide for the greatest
      number of patients. In this context, simple methods that would not necessarily
      entail the need for selected cell-processing facilities to ex vivo expand or
      improve the CB graft's functional activity may be of interest, with one such
      possibility being the use of an orally active inhibitor of the enzyme
      dipeptidylpeptidase 4, alone or in combination with other new and innovative
      approaches for improving HSC engraftment and in vivo repopulating capability of
      CB.

PMID- 24304087
TI  - Prevalence and factors associated with xerostomia and hyposalivation among
      community-dwelling older people in Japan.
AB  - OBJECTIVE: This study investigated the prevalence and factors associated with
      xerostomia and hyposalivation among community-dwelling older people. BACKGROUND:
      Xerostomia and hyposalivation are common symptoms in the older population.
      MATERIALS AND METHODS: This study included with 894 community-dwelling, Japanese
      older people (355 men, 539 women; age 65-84 years) who participated in a
      comprehensive geriatric health examination, which included questionnaires and
      interviews regarding medical history, medications, Tokyo Metropolitan Institute
      of Gerontology Index of Competence (TMIG-IC), depressive condition. The Zung Self
      Rating Depression Scale (SDS) was used to evaluate depression. Resting salivary
      flow rate was evaluated by the modified cotton roll method. RESULTS: In this
      study, 34.8% of the participants (mean age, 73.5 +/- 5.0 years) complained about
      xerostomia, while the prevalence of hyposalivation was 11.5%. Multiple regression
      analysis revealed hypnotics use [odds ratio (OR) = 1.71, 95% confidence interval
      (CI) = 1.13-2.61], SDS (OR = 1.05, CI = 1.04-1.07) and TMIG-IC total points (OR =
      0.87, CI = 0.76-0.99) to be significantly associated with xerostomia. In
      contrast, female gender (OR = 2.59, CI = 1.55-4.31) and the use of agents
      affecting digestive organs (OR = 1.78, CI = 1.11-2.86) were associated with
      hyposalivation. CONCLUSION: Our findings showed that the prevalence of xerostomia
      and hyposalivation were approximately 1 in 3 and 1 in 10 respectively. The
      factors associated with psychological factors and high-level functional
      competence, while hyposalivation was associated with medications and gender, as
      well as systemic and/or metabolic differences. It is important to consider these
      multidimensional factors associated with xerostomia and hyposalivation.

PMID- 24304088
TI  - Infrared studies of the reaction of methanesulfonic acid with trimethylamine on
      surfaces.
AB  - Organosulfur compounds generated from a variety of biological as well as
      anthropogenic sources are oxidized in air to form sulfuric acid and
      methanesulfonic acid (MSA). Both of these acids formed initially in the gas phase
      react with ammonia and amines in air to form and grow new particles, which is
      important for visibility, human health and climate. A competing sink is
      deposition on surfaces in the boundary layer. However, relatively little is known
      about reactions after they deposit on surfaces. We report here diffuse
      reflectance infrared Fourier transform spectrometry (DRIFTS) studies of the
      reaction of MSA with trimethylamine (TMA) on a silicon powder at atmospheric
      pressure in synthetic air and at room temperature, either in the absence or in
      the presence of water vapor. In both cases, DRIFTS spectra of the product surface
      species are essentially the same as the transmission spectrum obtained for
      trimethylaminium methanesulfonate, indicating the formation of the salt on the
      surface with a lower limit to the reaction probability of gamma > 10(-6). To the
      best of our knowledge, this is the first infrared study to demonstrate this
      chemistry from the heterogeneous reaction of MSA with an amine on a surface. This
      heterogeneous chemistry appears to be sufficiently fast that it could impact
      measurements of gas-phase amines through reactions with surface-adsorbed acids on
      sampling lines and inlets. It could also represent an additional sink for amines
      in the boundary layer, especially at night when the gas-phase reactions of amines
      with OH radical and ozone are minimized. 

PMID- 24304089
TI  - Transparent organosilica photocatalysts activated by visible light: photophysical
      and oxidative properties at the gas-solid interface.
AB  - The photophysical properties of several photosensitizers (PSs) included or
      grafted in silica monoliths were compared to their properties in solution. The
      effects of the solid support on their steady-state and transient absorption
      spectra, on their quantum yields of singlet oxygen ((1)O2) production, and on
      their ability to photoinduce the oxidation of dimethylsulfide (DMS) were
      investigated. Two cyanoanthracene derivatives (9,14-dicyanobenzo[b]triphenylene,
      DBTP, and 9,10-dicyanoanthracene, DCA), as well as three phenothiazine dyes
      (methylene blue, MB(+), new methylene blue, NMB(+), methylene violet, MV), were
      encapsulated in silica, analyzed and compared to two reference PSs
      (perinaphthenone, PN and rose bengal, RB). A DBTP derivative (3-[N-(N"
      triethoxysilylpropyl-N'-hexylurea)]carboxamido-9,14-dicyanobenzo[b]triphenylene,
      3) was also prepared and grafted onto silica. Thanks to the transparency and the
      free-standing shape of the monoliths, the complete spectroscopic characterization
      of the supported PSs was carried out directly at the gas-solid interface. The
      influence of the silica network, the PS, and the adsorption/grafting link between
      the PS and silica was investigated. The effects of PS concentration, gaseous
      atmosphere, humidity, and hydrophobicity on the production of (1)O2 were
      analyzed. With all PSs, (1)O2 production was very efficient (quantum yields of
      (1)O2 production, relative to PN, between 0.6 and 1), and this species was the
      only one involved in the pollutant photooxidation. The influence of the matrix on
      the PSs' photophysics could be considered as negligible. In contrast, the matrix
      effect on DMS photooxidation was extremely important: the gas diffusion inside
      the porous structure, and thus, the photoactivity of the materials, strictly
      depended on silica's surface area and porosity. Our results highlight the
      suitability of these silica structures as inert supports for the study of the
      photosensitizing properties at the gas-solid interface. Moreover, thanks to the
      adsorption properties of the matrix, the synthesized materials can be used as
      microphotoreactor for the (1)O2-mediated oxidation of volatile pollutants.

PMID- 24304090
TI  - Repetitive facilitative exercise under continuous electrical stimulation for
      severe arm impairment after sub-acute stroke: a randomized controlled pilot
      study.
AB  - OBJECTIVE: To investigate the effectiveness of repetitive facilitative exercise
      (RFE) under surface neuromuscular electrical stimulation (NMES) in patients with
      post-stroke hemiplegia. METHODS: This randomized, controlled, observer-blinded,
      pilot trial randomized 27 adults with severe arm impairment [Fugl-Meyer Arm scale
      (FMA) <= 20] due to stroke of 3-13 weeks duration into three groups and provided
      treatment on a 4-week, 40 minutes/day, 5 days/week schedule. The RFE-under-NMES
      group were given 100-150 repetitions of standardized movements of shoulder, elbow
      and wrist joints of their affected arm with concurrent low-amplitude NMES for
      each corresponding musculature. The RFE group was given the same exercise regimen
      but without NMES. The control group was treated with a conventional arm
      rehabilitation programme without NMES. FMA was assessed at baseline and 4 weeks.
      RESULTS: All 27 participants (nine in each group) completed the trial. At 4
      weeks, the RFE-under-NMES group evidenced significantly greater improvement
      compared with the control group on the FMA (p = 0.003), but not with the RFE
      group (p = 0.092). The RFE group showed improvement compared with the control
      group, but it was not significant (p = 0.199). CONCLUSIONS: RFE under NMES is
      feasible in clinical settings and may be more effective than conventional
      rehabilitation in lessening arm impairment after sub-acute stroke.

PMID- 24304091
TI  - Tin-mediated regioselective benzylation and allylation of polyols: applicability
      of a catalytic approach under solvent-free conditions.
AB  - The first catalytic version of the stannylene-mediated benzylation and allylation
      of polyols is reported. The methodology is based on a simple solvent-free
      protocol that significantly advances, in terms of both experimental ease and
      synthetic scope, the applicability of tin-promoted selective protections. The
      described approach is indeed endowed with a very large number of advantages over
      routine protocols: use of a low catalytic loading of cheap Bu2SnO, a single-step
      process with avoided use of solvents, a minimally demanding experimental
      procedure with reactions performed under air, reduced reaction times, a much
      simpler work up, a wide target scope, and yields that, in many cases, compare
      favorably to routine protocols. In addition, the catalytic solvent-free approach
      extends the scope of stannylene chemistry to unprecedented applications to
      reducing sugars and in the synthesis of highly benzylated building blocks
      otherwise accessed through much more demanding procedures. From a conceptual
      point of view, the described results indicate that solvent-free conditions can
      assist the development of catalytic approaches otherwise ineffective in solution.

PMID- 24304092
TI  - Impact of symptom improvement on patients' bother and quality of life in female
      patients with overactive bladder treated by solifenacin (SET-Q).
AB  - OBJECTIVES: To analyze the relationship between symptom improvement and health
      related quality of life in female overactive bladder patients treated with
      solifenacin. METHODS: We carried out a prospective, multicenter, open-label
      study. Eligible patients were treatment-naive female patients with overactive
      bladder, with an urgency episode at least once a week. Symptoms were
      quantitatively assessed by the Overactive Bladder Symptom Score, and quality of
      life by the Overactive Bladder questionnaire. Changes of symptom severity,
      bother, and quality of life were assessed at baseline and 12 weeks after
      treatment with solifenacin 5, 7.5 or 10 mg once daily. RESULTS: Data from 523
      patients (mean age 66 years) were analyzed. Solifenacin significantly improved
      the total Overactive Bladder Symptom Score and also all subscores for the four
      symptoms (daytime frequency, urgency, night-time frequency and urgency
      incontinence). Solifenacin also significantly improved the four quality of life
      subscales, total quality of life and symptom bother scores of the Overactive
      Bladder questionnaire. The severity of night-time frequency at baseline
      positively affected the improvement in the quality of life subscale of Sleep, and
      the severity of daytime frequency at baseline positively affected the improvement
      of coping and social interaction. Improvement of severity in various symptoms
      positively affected the improvement of bother and the quality of life subscales.
      CONCLUSIONS: Solifenacin provides an overall improvement of bother and quality of
      life in female overactive bladder patients. Symptom severity before treatment and
      improvement of symptom severity seem to variably affect this improvement.

PMID- 24304093
TI  - Using applied behavior analysis and smart technology for meeting the health needs
      of individuals with intellectual disabilities.
AB  - OBJECTIVE: Individuals with intellectual disabilities often have special
      healthcare concerns such as diabetes, kidney disease, severe allergies,
      progressive illnesses, respiratory weaknesses, and obesity. Smart technology can
      be an asset for individuals with intellectual disabilities for better managing
      their healthcare needs. METHODS: A critical review of the literature related to
      applied behavior analysis, smart technology, and health needs of individuals with
      intellectual disabilities was conducted. RESULTS: This discussion paper describes
      factors that contribute to the successful use of smart technology for the health
      issues of individuals with intellectual disabilities. CONCLUSIONS: We see key
      components in developing appropriate access and use of smart technology for the
      health of people with intellectual disabilities being: (a) systematic
      instructional methods for consistent and accurate use of the technology, (b)
      modifying the current technology for people with intellectual disabilities,

PMID- 24304094
TI  - Green emitting photoproducts from terrylene diimide after red illumination.
AB  - The spectral properties of emissive photoproducts, formed upon 633 nm irradiation
      of a terrylene diimide dye, were investigated. Ensemble and single-molecule level
      experiments were conducted by immobilizing the TDI dye molecules in a polystyrene
      film. In the bulk experiments, green emission could be observed from the
      photobleached areas (photobleached with 633 nm light) when excited with 480 or
      514 nm light. Similar phenomena were also observed at the single-molecule level.
      On the basis of the single-molecule experiments, a conversion efficiency of about
      5% was estimated for the formation of emissive spectrally blue-shifted
      photoproducts. These green emissive photoproducts have spectral properties that
      resemble those of lower rylene homologues, e.g. perylene diimide or perylene
      monoimide. Our results indicate that the formation of blue-shifted emissive
      photoproducts can have implications for analyzing single-molecule FRET
      experiments or multiple color-labeled fluorescent systems. 

PMID- 24304095
TI  - Next-generation sequencing for molecular ecology: a caveat regarding pooled
      samples.
AB  - We develop a model based on the Dirichlet-compound multinomial distribution (CMD)
      and Ewens sampling formula to predict the fraction of SNP loci that will appear
      fixed for alternate alleles between two pooled samples drawn from the same
      underlying population. We apply this model to next-generation sequencing (NGS)
      data from Baltic Sea herring recently published by (Corander et al., 2013,
      Molecular Ecology, 2931-2940), and show that there are many more fixed loci than
      expected in the absence of genetic structure. However, we show through coalescent
      simulations that the degree of population structure required to explain the
      fraction of alternatively fixed SNPs is extraordinarily high and that the surplus
      of fixed loci is more likely a consequence of limited representation of
      individual gene copies in the pooled samples, than it is of population structure.
      Our analysis signals that the use of NGS on pooled samples to identify divergent
      SNPs warrants caution. With pooled samples, it is hard to diagnose when an NGS
      experiment has gone awry; especially when NGS data on pooled samples are of low
      read depth with a limited number of individuals, it may be worthwhile to temper
      claims of unexpected population differentiation from pooled samples, pending
      verification with more reliable methods or stricter adherence to recommended
      sampling designs for pooled sequencing e.g. Futschik & Schlotterer 2010,
      Genetics, 186, 207; Gautier et al., 2013a, Molecular Ecology, 3766-3779).
      Analysis of the data and diagnosis of problems is easier and more reliable (and
      can be less costly) with individually barcoded samples. Consequently, for some
      scenarios, individual barcoding may be preferable to pooling of samples.

PMID- 24304096
TI  - Measuring blood pressure in pregnancy and postpartum: assessing the reliability
      of automated measuring devices.
AB  - OBJECTIVE: To determine the reliability of automated blood pressure (BP)
      measuring devices in hypertensive pregnancies. METHODS: Three sequential
      measurements were taken using mercury sphygmomanometry and an automated device in
      pregnant hypertensive women (n = 89). RESULTS: Systolic BP (SBP) was higher with
      the automated device (mean difference 2.5 mmHg, 95% CI: 1.9-3.2 mmHg), whereas
      diastolic BP (DBP) was higher with the mercury sphygmomanometer (mean difference
      2.0 mmHg, 95% CI: 1.5-2.6 mmHg). Within-patient variability for the automated
      device was: SBP 4.8 mmHg (95% CI: 4.6-5.2 mmHg), DBP 3.4 mmHg (95% CI: 3.1-3.7
      mmHg); and for mercury sphygmomanometry: SBP 3.7 mmHg (95% CI: 3.5-4.0 mmHg), DBP
      3.0 mmHg (95% CI: 2.8-3.3 mmHg). CONCLUSION: Outpatient automated BP measurement
      agrees well with mercury sphygmomanometry in hypertensive pregnancies.

PMID- 24304097
TI  - Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in
      pharmaceutical and biomedical applications.
AB  - INTRODUCTION: Thermogelling chitosan (CS)/glycerophosphate (GP) solutions have
      been reported as a new type of parenteral in situ forming depot system. These
      free-flowing solutions at ambient temperature turn into semi-solid hydrogels
      after parenteral administration. AREAS COVERED: Formulation parameters such as CS
      physico-chemical characteristics, CS/gelling agent ratio or pH of the system,
      were acknowledged as key parameters affecting the solution stability, the sol/gel
      transition behavior and/or the final hydrogel structure. We discuss also the use
      of the standard CS/GP thermogels for various biomedical applications, including
      drug delivery and tissue engineering. Furthermore, this manuscript reviews the
      different strategies implemented to improve the hydrogel characteristics such as
      combination with carrier particles, replacement of GP, addition of a second
      polymer and chemical modification of CS. EXPERT OPINION: The recent advances in
      the formulation of CS-based thermogelling systems already overcame several
      challenges faced by the standard CS/GP system. Dispersion of drug-loaded carrier
      particles into the thermogels allowed achieving prolonged release profiles for
      low molecular weight drugs; incorporation of an additional polymer enabled to
      strengthen the network, while the use of chemically modified CS led to enhanced
      pH sensitivity or biodegradability of the matrix.

PMID- 24304098
TI  - Novel flow cytometric screening method for bacterial contamination of red blood
      cells: a proof-of-principle evaluation.
AB  - BACKGROUND: Platelet concentrates (PCs) are the major source of transfusion
      transmitted bacterial infection but the significantly higher number of transfused
      red blood cells (RBCs) has resulted in a similar occurrence of possible
      transfusion-associated bacterial infections as those of recipients transfused
      with platelets. The aim of this study was adaption of the BactiFlow (BF) flow
      cytometric rapid PC screening method for the detection of bacterial contamination
      in RBCs. STUDY DESIGN AND METHODS: The BF assay was used to detect and count
      bacteria based on esterase activity in viable cells in RBCs. The initial sample
      preparation for RBCs included the lysis of RBCs, followed by enrichment of
      bacteria by centrifugation and subsequent standard PC sample preparation. Two
      hundred RBC units were analyzed by BF and the BacT/Alert automated culture
      system. Furthermore, RBCs were spiked with eight different bacteria to monitor
      bacterial growth kinetics. RESULTS: The BF showed an excellent correlation to
      conventional plate count results after RBC sample processing. The diagnostic
      sensitivity of the assay was determined to fewer than 500 counts/mL. Analysis of
      RBC units showed concordant negative results by BF and culture. Growth kinetics
      of bacteria were successfully monitored using flow cytometry, showing that
      Yersinia enterocolitica or Serratia liquefaciens had the capability to grow in
      RBCs to high counts. CONCLUSION: Our study demonstrates the successful
      modification and application of a rapid flow cytometric screening method for
      bacterial contamination in RBCs. The BF assay represents a powerful basic tool to
      study bacterial contamination, potential screening strategies of RBCs, and the
      clinical outcome of screened RBCs prepared for transfusion.

PMID- 24304099
TI  - Clinical evaluation of coronally advanced flap with or without acellular dermal
      matrix graft on complete defect coverage for the treatment of multiple gingival
      recessions with thin tissue biotype.
AB  - AIM: The objective of this study was to compare acellular dermal matrix graft
      (ADM) combination with coronally advanced flap (CAF) on complete defect coverage,
      aesthetics and patient satisfaction with CAF alone for multiple recessions with
      gingival thickness (GT) <0.8 mm. MATERIALS AND METHODS: Forty-eight Miller Class
      I multiple recessions >=3 mm were divided into test (CAF + ADM) and control (CAF)
      groups. At baseline and 12 months, recession height (RH), keratinized tissue
      height (KT), GT, mean and complete defect coverage were evaluated. Patient
      satisfaction, root coverage aesthetic score (RES) and the correlation between GT
      and defect coverage were also assessed. RESULTS: Baseline RH in CAF + ADM and CAF
      groups was 3.25 +/- 0.34 mm and 3.21 +/- 0.26 mm, respectively. Mean and complete
      defect coverage were 94.84% and 83.33% in test group, 74.99% and 50.00% in
      control group, respectively. Inter-group differences were found to be
      statistically significant for RH reduction, attachment gain, KT and GT increase,
      mean defect coverage and RES in favour of test group (p < 0.05). There was a
      significant positive correlation between GT and mean defect coverage (p < 0.05).
      CONCLUSION: Coronally advanced flap in association with ADM can be proposed as a
      valid approach for the treatment of multiple recessions with thin tissue biotype.

PMID- 24304100
TI  - A variant in MYO10 is associated with hind limb conformation in Swiss Large White
      boars.

PMID- 24304101
TI  - ATP P2Y1 receptors control cognitive deficits and neurotoxicity but not glial
      modifications induced by brain ischemia in mice.
AB  - ATP is a pleiotropic cell-to-cell signaling molecule in the brain that functions
      through activation of the P2 receptors (P2R), encompassing ionotropic P2XR or
      metabotropic P2YR. Noxious brain insults increase the extracellular levels of ATP
      and previous studies have implicated different P2R, namely P2Y1R, in the control
      of ischemic brain damage, but it remains to be defined if P2Y1R antagonists also
      alleviate the behavioral impairments associated with brain ischemia. Furthermore,
      as P2Y1R can control neuronal and glial functions, we explored if P2Y1R
      antagonist-mediated protection would mainly involve neuronal and/or glial
      processes. Adult male mice subject to permanent middle cerebral artery occlusion
      (pMCAO) displayed an infarcted cortical area (2,3,5-triphenyltetrazolium chloride
      staining), decreased neurological score with decreased working and reference
      memory performance (Y-maze, object recognition and aversive memory), accompanied
      by neuronal damage (FluoroJade C), astrogliosis (glial fibrillary acidic protein)
      and microgliosis (CD11b). All of these changes were attenuated by
      intracerebroventricular pre-treatment (10 min before pMCAO) with the generic P2R
      antagonist 4-[(E)-{4-formyl-5-hydroxy-6-methyl-3-[(phosphono-oxy)methyl]pyridin-2
      yl}diazenyl]benzene-1,3-disulfonic acid (PPADS, 0.5-1.0 nmol/MUL). In contrast,
      the selective P2Y1R antagonist (1R*,2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]
      2-(phosphono-oxy)bicycle[3.1.0] hexane-1-methanol dihydrogen phosphate ester
      (MRS2500, 1.0-2.0 nmol/MUL) afforded equivalent behavioral benefits but only
      prevented neuronal damage but not astrogliosis or microgliosis upon pMCAO. These
      results indicated that P2Y1R-associated neuroprotection mainly occurred through
      neuronal mechanisms, whereas other P2R were also involved in the control of
      astrocytic reactivity upon brain injury.

PMID- 24304102
TI  - Structural and energetic analyses of SNPs in drug targets and implications for
      drug therapy.
AB  - Mutations in drug targets can alter the therapeutic effects of drugs. Therefore,
      evaluating the effects of single-nucleotide polymorphisms (SNPs) on drug-target
      binding is of significant interest. This study focuses on the analysis of the
      structural and energy properties of SNPs in successful drug targets by using the
      data derived from HapMap and the Therapeutic Target Database. The results show
      the following: (i) Drug targets undergo strong purifying selection, and the
      majority (92.4%) of the SNPs are located far from the drug-binding sites (>12 A).
      (ii) For SNPs near the drug-binding pocket (<=12 A), nearly half of the drugs are
      weakly affected by the SNPs, and only a few drugs are significantly affected by
      the target mutations. These results have direct implications for population-based
      drug therapy and for chemical treatment of genetic diseases as well. 

PMID- 24304104
TI  - Skeletal evidence of trepanning on a 5th century skull from Ludbreg, Croatia.
AB  - This paper presents a case of skull trepanation from the town of Ludbreg in north
      western Croatia. This is the second case of trepanation reported in human
      skeletal remains from archaeological sites in Croatia. The procedure was
      performed on an adult male buried in a tomb under tegulae at the "Somodi Garden"
      site. The archaeological context and radiocarbon analysis date the bone sample to
      the 5th century AD, i.e. to the Migration Period. The trepanned aperture is
      located on the left side of the frontal bone and the left parietal bone. The
      lesion is oval in shape with all three layers of the calvarium breached, leaving
      dura mater exposed. This neurosurgical intervention was most probably performed
      by scraping for therapeutic reasons (head injury). The morphology of the lesion
      strongly indicates that the individual survived the operation and lived for a
      longer period of time, several years at least.

PMID- 24304103
TI  - Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody
      associated vasculitis: a prospective pharmacokinetics and clinical study.
AB  - Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment
      strategy is based on immunosuppressive agents. Little information is available
      concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients
      treated for AAV. We evaluated the variations in pharmacokinetics for MPA in
      patients with AAV and the relationship between MPA-AUC and markers of the
      disease. MPA blood concentrations were measured through the enzyme-multiplied
      immunotechnique (C(0), C(30), C(1), C(2), C(3), C(4), C(6) and C(9)) to determine
      the AUC. Eighteen patients were included in the study. The median (range) MPA
      AUC(0-12) was 50.55 (30.9-105.4) mg/h/l. The highest coefficient of determination
      between MPA AUC and single concentrations was observed with C(3) (P < 0.0001) and
      C(2) (P < 0.0001) and with C(4) (P < 0.0005) or C(0) (P < 0.001). Using linear
      regression, the best estimation of MPA AUC was provided by a model including
      C(30), C(2) and C(4): AUC = 8.5 + 0.77 C(30) + 4.0 C(2) + 1.7 C(4) (P < 0.0001).
      Moreover, there was a significant relationship between MPA AUC(0-12) and
      lymphocyte count (P < 0.01), especially CD19 (P < 0.005), CD8 (P < 0.05) and CD56
      (P < 0.05). Our results confirm the interindividual variability of MPA AUC in
      patients treated with MMF in AAV and support a personalized therapy according to
      blood levels of MPA.

PMID- 24304105
TI  - Benefits of lethal pandemics: direct impact of contagious diseases on public
      administration in Hungary (1867-1914).
AB  - The reconciliation of 1867 between Austria and Hungary brought great changes to
      Hungarian public administration: the way towards the building up of a modern
      public administration had been opened. Although there was a functioning public
      health system and a related legislation from the late 18th century, major issues 
      such as balanced geographical distribution of medical personnel, fair access to
      medical services even in the poorer regions of the country, and the effective
      protection against some contagious diseases - were not resolved for decades.
      During the reform work of public administration since the 1870s, the lawmakers
      touched repeatedly the framework and functioning of the public health as well.
      Although the general conditions of the domain depended traditionally on the
      municipalities and counties due to the national importance of the matter, the
      government made efforts to make the functioning of the public health more
      efficient through centralisation. The contagious diseases continuously endangered
      the population, revealing the weak points in the existing public health system,
      thereby giving a momentum to the reforms and helping the government in its
      organization of prevention and clearly contributing to the legislation work.

PMID- 24304106
TI  - [Notes on the abandoned construction project for the provincial psychiatric
      hospital in Istria in the second half of the nineteenth century].
AB  - Records about the need for a psychiatric hospital in Istria date back to the
      early 19th century). This article presents the views on the issue expressed by
      advisors of the National Council of Istria more than half a century later. It
      starts with the session held on 15 March 1864 and follows the development of
      views the National Council held, from the motion to build a new mental hospital
      in at the feet of Monte Ghiro to the actual construction of the "Santorio
      Santorio" Provincial Hospital (still existing) at the hill of St Mihovil in Pula.
      The paper also investigates the reasons why the Council advisors abandoned the
      project of building the psychiatric hospital in Istria in favour of a home for
      the mentally ill in Trieste, where many Istrian patients were provided
      accommodation from as early as the end of the eighteenth century until the end of
      World War II. During the rule of the Habsburg Monarchy, many other cities of the
      Empire hospitalised mental patients from Istria, whose pitiful condition was
      reported by Matteo Campitelli at the session of the Istrian Provincial Parliament
      in 1886. 

PMID- 24304107
TI  - [Dr.s Ljubica Bosner (1902- 1991): a surgeon, obstetrician, and gynaecologist].
AB  - Ljubica Bosner, MD (2 February 1902 - 21 October 1990) was a distinguished woman
      surgeon, who worked in Rijeka, and all over Croatia, including the posts in
      Ogulin, Bjelovar, Petrinja, and VaraZdin, that are marginally known to wider
      medical circles and general public from her biography. Archive records point to
      her beginnings as a surgeon at the regional hospital of Ogulin in the 1930s, and
      then at the Department of Surgery and Gynaecology of the regional hospital and
      later state hospital of Bjelovar, where she had operated over the first two years
      of World War 2. From the end of 1942 to May 1943, she worked as a surgeon and the
      head of the hospital in Petrinja, and then as the head of the Soft Tissue Unit,
      Department of Surgery at Rebro Hospital in Zagreb until May 1945. She then headed
      the hospital in Mali Losinj until 1946 and moved to the Sobol Brothers Hospital
      in Rijeka, where she worked until retirement. Ljubica Bosner was one of the few
      women who had spent all her working life in general surgery, gynaecology and
      obstetrics, war surgery, and later paediatric surgery. Thousands of surgery
      records witness to her unrelenting dedication and high professionalism in regular
      as well as in emergency war situations. Her mentorship, loyalty to colleagues and
      medicine, social sensitivity and good will are still being recalled by her
      students.

PMID- 24304108
TI  - [Formal, functional, and fashionable: nurse uniforms in Croatia between the 1920s
      and 1940s].
AB  - This article recollects the development of the official uniforms of graduate
      nurses in Croatia from the early 1920s to the 1940s. These were the early days of
      a profession that has gained its authority not only in health care, but also in
      social work, especially when it comes to health education and social support.
      This new profession called for a clear visual identity that would appropriately
      represent its status and the competence of the women who wore the uniforms. The
      article follows the line of continuity in the design and symbols of nurse
      clothing over the early days of the profession. 

PMID- 24304109
TI  - Success of long bone fracture healing in ancient Egypt: a paleoepidemiological
      study of the Giza Necropolis skeletons.
AB  - Complications may provide information regarding the management of fractures in
      ancient populations. The aim of this study was to determine the rates of long
      bone fractures and the proportion of misalignments as indicators of failed
      treatment or no treatment at all in skeletons from the Giza Necropolis dating to
      the Old Kingdom period (2700-2190 BC). We visually examined for fractures 2287
      long bones of 204 adult skeletons (112 male and 92 female) and took x-rays of
      fractured bones in standard AP and ML views, so that we can analyse
      misalignments. Fractures were found in 45 of the 2287 examined long bones (1.97
      %). Most of the fractures healed with good alignment, most likely as a result of
      successful treatment, and only three fractures showed misalignment. 

PMID- 24304110
TI  - [Health culture in the Statute of Lastovo].
AB  - The aim of this article was to define the elements of health culture in the
      Statute of Lastovo, from its declaration in 1310 to amendments made in the 18th
      century. The source we used was a recently published translation of the Statute
      from Latin, in which we identified the lawmaker's stipulations directly or
      indirectly related to public health of the times. The Statute stipulates several
      preventive measures to keep plague at bay and to control it if it breaks out.
      Stipulations on communal slaughterhouses and fish markets, even if not directly
      intended to address healthcare issues, brought a definite improvement to public
      hygiene and sanitation. Penal provisions for the perpetrators included death,
      whipping, branding, cutting fingers off, standing on logs, and pillorying. The
      article concludes that even though the Statute of Lastovo is quite comprehensive
      and voluminous, it does not give much space to health culture, in fact, even less
      space than other Medieval statutes of towns along the east coast of the Adriatic.

PMID- 24304111
TI  - An investigation into the ancient abortion laws: comparing ancient Persia with
      ancient Greece and Rome.
AB  - Since the dawn of medicine, medical rights and ethics have always been one of
      mankind's concerns. In any civilisation, attention paid to medical laws and
      ethics depends on the progress of human values and the advancement of medical
      science. The history of various civilisations teaches that each had its own views
      on medical ethics, but most had something in common. Ancient civilisations such
      as Greece, Rome, or Assyria did not consider the foetus to be alive and therefore
      to have human rights. In contrast, ancient Persians valued the foetus as a living
      person equal to others. Accordingly, they brought laws against abortion, even in
      cases of sexual abuse. Furthermore, abortion was considered to be a murder and
      punishments were meted out to the mother, father, and the person performing it. 

PMID- 24304112
TI  - Physician and dictator: a pictorial essay on Luigi Carlo Farini (1812-1866) in
      his homeland.
AB  - Luigi Carlo Farini (1812-1866) was one of the leading figures in the Italian
      unification, the Risorgimento. As a physician he always took care of the health
      problems of its people with a broadminded attitude, promoting for example
      extensive campaigns of Jennerian vaccination or experimenting the effects of
      electricity on tetanus. As a political leader - he was proclaimed "Dictator" in
      1859 - he made possible the annexation of the Adriatic regions of Emilia and
      Romagna to the Kingdom of Vittorio Emanuele II of Savoy that later, in March
      1861, was to become the new Kingdom of Italy. This article, in connection with
      the project "Himetop - The History of Medicine Topographical Database", offers a
      brief photographic survey of the location and condition of the monuments and
      memories of the physician-dictator in his homeland, two hundred years after his
      birth. Not only the tormented history of his monument in Ravenna, but also his
      birthplace, hospital, tomb, etc., testify that Farini's memory is well preserved
      among the people he served as a physician and as a statesman.

PMID- 24304113
TI  - Italian contributions to Turkish paediatrics during the Ottoman Empire.
AB  - The Ottoman Empire maintained close relations with the neighbouring Italian city
      states in the 16th and 17th century. Yacub Pasha (1425-1481), personal physician
      of Mehmed II the Conqueror, was an Italian Jew who advanced to the title of pasha
      and vizier. Domenico Hierosolimitano (ca. 1552-1622), the third physician to
      Sultan Murad III, was a Jerusalemite rabbi. His book is an important source about
      everyday life and medical practice in Istanbul at the time. Nuh bin Abd al-Mennab
      (1627-1707), also of Italian stock, was the Chief Physician of the Ottoman
      Empire, who translated a pharmacopoeia into Turkish. In the same century, two
      Italians, Israel Conegliano (Conian) and Tobia Cohen became private physicians to
      leading Ottoman pashas and the Grand Vizier. A. Vuccino (1829-1893) and Antoine
      Calleja Pasha (1806-1893) taught at the Istanbul Medical School. Italy was a
      favoured country for medical education during the early period of Ottoman
      westernisation. Sanizade Mehmet Ataullah Efendi (1771-1826) translated the first
      medical book printed in the Ottoman Empire from Italian into Turkish. Mustafa
      Behcet Efendi (1774-1833), chief physician to the Sultan and the founder of the
      first western medical school in Turkey, translated several medical books from
      Italian into Turkish. The first printed pharmacopeia in the Ottoman Empire was
      also originally Italian In the 19th century, Edouard Ottoni and his son Giuseppe
      Ottoni were well-known military pharmacists, both under the name of Faik Pasha.
      Probably the most influential physician of Italian origin was Giovanni Battista
      Violi (1849-1928), who had practiced paediatrics in Turkey for more than fifty
      years. Violi was the founder of the first children's hospital, the first vaccine
      institute, and the first paediatric journal in the Ottoman Empire.

PMID- 24304114
TI  - Anatomy and physiology in the work of Nemesius of Emesa "On the Nature of Man".
AB  - This study summarises the original medical information contained in the treatise
      On the Nature of Man by the Byzantine scholar Nemesius, Bishop of Emesa (4th
      century), written in ancient Greek. Nemesius' work had a strong impact on later
      Byzantine scholarship, as witnessed by a number of treatises on human body that
      followed under a similar or identical title. This review introduces and
      summarises some of the basic views of Nemesius and compares them with those of
      Galen, one of the major contributors to medical knowledge of antiquity, in order
      to see how Galen's theories on anatomy and physiology influenced Nemesius. We
      conclude that the medical information in the work of Nemesius reflects the high
      level of Byzantine medicine of the time, as well as deep influences from ancient
      Greek intelligentsia and Galen in particular. 

PMID- 24304115
TI  - Physicians and architects - not an odd couple.
AB  - One may think that there is no apparent interface between so different
      occupations as medicine and architecture. The historical and present-day
      connections between these academic fields resulted in the creation of healthy
      environment, housing and hospital. This article also speaks about another meeting
      point of these professions: physicians who became architects (or amateur
      architects) and personal friendships between physicians, scientists, and
      architects which resulted in fruitful and progressive architectural creations.
      Both professions may be regard as art and science as well. 

PMID- 24304116
TI  - [Arturo Beretta and the "trophomicrobic theory of the caries"].
AB  - The most original contribution made by the Italian School to the study of caries
      aetiology is undoubtedly the "trophomicrobic theory" proposed by Arturo Beretta,
      the first teacher of dentistry at the University of Bologna in 1918. This article
      brings biographical and bibliographical notes about Beretta (who was, among other
      things, Dean of the Faculty of Medicine of Bologna and Senator), and summarises
      the principles of his theory, which adds to Miller's "chemical-parasitic" theory
      of caries-predisposing properties of the enamel and host saliva. It also recalls
      the work of major Italian and non-Italian researchers who have used or modified
      Beretta's idea. 

PMID- 24304117
TI  - A concise history of forensic medicine in Czech Republic.
AB  - This paper presents the most important historical facts about all forensic
      medicine workplaces in the Czech Republic since the beginning till present day,
      including a perspective on how to establish a new one. Each of the University
      Forensic Medicine Institutes or district Departments is covered by at least one
      author. The oldest institute is in Prague and in Brno, the youngest is in
      Pardubice. 

PMID- 24304118
TI  - Ant mandibles as staples in the era of Greek patriot Ioannis Makriyannis (1797
      1864).
AB  - The use of ant mandibles as surgical clips was documented by the ancient Indian
      physicians Susruta and Charaka as early as 1000 BC and continued in some world
      areas into the early 1900s. According to the memoirs of the Greek revolutionary
      general Ioannis Makriyannis, this technique was also applied in the battlefields
      of the Greek Revolution for Independence between 1821 and 1832.

PMID- 24304119
TI  - An asthma sports camp series to identify children with possible asthma and
      cardiovascular risk factors.
AB  - BACKGROUND: The prevalence of asthma and obesity in children has increased over
      the past several years, with obesity being associated with higher rates of
      asthma. In response to known disparities in asthma prevalence and morbidity,
      along with barriers to diagnosis, assessment and education, a comprehensive
      asthma sports camp series was developed and implemented. OBJECTIVE: The primary
      objective was to evaluate the effectiveness of utilizing a sports camp model to
      identify children with undiagnosed and uncontrolled asthma, and to provide
      recommendations for follow-up care. The secondary objectives were to identify the
      presence of and associations between related co-morbidities and risk factors for
      asthma morbidity such as obesity, hypertension and exposure to tobacco smoke; and
      to assess asthma medication use. METHODS: Six daylong camps at an inner-city
      university were offered to children 5-17 years of age over a period of two years.
      Asthma, body mass index, blood pressure (BP) and carbon monoxide screenings were
      conducted at each camp. RESULTS: In this sample, 43.7% of children had previously
      diagnosed asthma, and 12.6% were classified as having potential, undiagnosed
      asthma. Of the children with previously diagnosed asthma, 76% were considered
      uncontrolled. Thirty-eight percent were determined to be overweight or obese and
      17% had elevated BP. CONCLUSIONS: An interdisciplinary sports camp model can be
      used to identify children with undiagnosed and uncontrolled asthma and
      cardiovascular risk factors; and to provide recommendations for follow-up care.

PMID- 24304120
TI  - Expression of midkine in normal human skin, dermatitis and neoplasms: association
      with differentiation of keratinocytes.
AB  - Midkine is a 13-kDa heparin-binding growth factor. It promotes growth, survival,
      migration and gene expression of various target cells and play roles in many
      diseases. In normal adult tissues, midkine expression is highly restricted;
      however, midkine expression levels are high in various malignant tumors. The
      major biological roles of midkine can be categorized into three areas, namely,
      the nervous system, cancer and inflammation. Thus far, midkine has not been
      studied extensively in diseased human skin. We performed immunohistochemistry
      tests by using anti-midkine antibodies to study the expression of midkine in
      normal skin and skin samples of 26 different cutaneous diseases. In addition, we
      investigated the expression pattern of the midkine gene in cultured
      keratinocytes. In normal skin, midkine expression was observed in the secretory
      coils of the eccrine sweat glands, outer root sheath and inner root sheath. Among
      the cutaneous tumors, the majority of keratinocyte-derived neoplasms were
      positive for midkine. Tumors that were not derived from keratinocytes were
      negative for midkine. In cultured keratinocytes, the midkine gene was expressed
      earlier than the genes required for keratinization, for example, cytokeratin 10
      and transglutaminase 1. Because midkine is expressed in the keratinized areas of
      normal skin, neoplasms and inflammation, it may play a role as a modulator of
      keratinization in the skin. 

PMID- 24304121
TI  - Emerging respiratory viruses: is it 'much ado about nothing'? (Shakespeare).

PMID- 24304123
TI  - Total synthesis of microtubule-stabilizing agent ceratamine A.
AB  - The total synthesis of ceratamine A, a natural microtubule-stabilizing agent with
      unusual cellular effects, has been accomplished starting from 5
      methoxybenzimidazole in 10 steps in an overall yield of 12.7%. The key steps in
      the synthesis involved the Schmidt rearrangement to construct the azepine ring,
      the alkylation of lactam to introduce the C-5 benzylic side chain, and the highly
      economical SNAr reaction to install the C-2 methylamine residue. 

PMID- 24304122
TI  - Functional outcome and quality of life in Tourette's syndrome after deep brain
      stimulation of the posteroventrolateral globus pallidus internus: long-term
      follow-up.
AB  - OBJECTIVES: Deep brain stimulation (DBS) for Tourette's syndrome (TS) in various
      targets has been in the focus for some years. However, there are hardly any data
      on "psychosocial" outcome after DBS for TS. The aim of the present study
      therefore was to focus on the functional outcome and "psychosocial changes" in TS
      patients after DBS. METHODS: Six patients with treatment-refractory TS underwent
      GPi-DBS. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate
      symptomatic outcome. Psychosocial changes were assessed applying the Global
      Assessment of Functioning Scale (GAF) and the Gilles-de-la-Tourette-Syndrome
      Quality-of-Life scale (GTS-QOL) with additionally documenting psychosocial
      changes. Follow-up ranged between 12 and 72 months. RESULTS: In all symptomatic
      responders (4 of 6) we found a significant functional improvement (mean GAF
      increasing from 53.75 (+/- 7.5) pre-operatively to 83.75 (+/- 7.5) at last follow
      up) along with a positive correlation with the course of GTS-QOL (R(2) = 0.62).
      CONCLUSIONS: Treatment success should not only be assessed with the classic "tic
      scales", but also with the GAF and GTS-QOL. Although improvement of tics seems to
      be positively correlated with improved functional outcome, symptomatic
      improvement may lead to unexpected major psychosocial changes - which both the
      patient and the clinicians in charge - should be prepared for.

PMID- 24304124
TI  - Insecticide washoff from concrete surfaces: characterization and prediction.
AB  - Pesticide runoff from impervious surfaces is a significant cause of aquatic
      contamination and ecologic toxicity in urban waterways. Effective mitigation
      requires better understanding and prediction of off-site transport processes.
      Presented here is a comprehensive study on pesticide washoff from concrete
      surfaces, including washoff tests, experimental data analysis, model development,
      and application. Controlled rainfall experiments were conducted to characterize
      washoff loads of commercially formulated insecticides with eight different active
      ingredients. On the basis of the analysis of experimental results, a
      semimechanistic model was developed to predict pesticide buildup and washoff
      processes on concrete surfaces. Three pesticide product specific parameters and
      their time dependences were introduced with empirical functions to simulate the
      persistence, transferability, and exponential characteristics of the pesticide
      washoff mechanism. The parameters were incorporated using first-order kinetics
      and Fick's second law to describe pesticide buildup and washoff processes,
      respectively. The model was applied to data from 21 data sets collected during 38
      rainfall events, with parameters calibrated to pesticide products and
      environmental conditions. The model satisfactorily captured pesticide mass loads
      and their temporal variations for pesticides with a wide range of chemical
      properties (log KOW = 0.6-6.9) under both single and repeated (1-7 times)
      rainfall events after varying set times (1.5 h~238 days after application).
      Results of this study suggested that, in addition to commonly reported
      physicochemical properties for the active ingredient of a pesticide product,
      additional parameters determined from washoff experiments are required for risk
      assessments of pesticide applications on urban impervious surfaces. 

PMID- 24304125
TI  - Quality of life impairment in children and adolescents with vitiligo.
AB  - Vitiligo significantly affects quality of life (QOL) in adults, but little is
      known about the effect on QOL of pediatric vitiligo and whether the extent,
      distribution, and duration of vitiligo are associated with QOL. We performed an
      online parental questionnaire-based study (N = 350) regarding children ages 0 to
      17 years with vitiligo, including validated questions about body surface area
      (BSA), distribution, and age of onset of vitiligo, associated symptoms, and QOL
      using the Children's Dermatology Life Quality Index (CDLQI). Vitiligo negatively
      affected numerous aspects of and total CDLQI score (median 3.0, interquartile
      range 5.0). Their vitiligo lesions did not bother only 4.1% of teenagers ages 15
      to 17 years, versus 45.6% of children ages 0 to 6 years and 50.0% of those ages 7
      to 14 years (p < 0.001). There was no association between the child's age and
      whether the child's vitiligo bothered the parents (p = 0.27). The most bothersome
      sites of vitiligo lesions for children and parents were the face (25.6% and
      37.4%, respectively) and legs (26.2% and 26.2%, respectively). Eighty-two
      patients (30.1%) reported itching and painful skin within the past week. Using
      multivariate ordinal logistic regression models, it was found that an affected
      BSA of more than 25% was associated with self-consciousness, difficulty with
      friendships and schoolwork, and teasing and bullying. Lesions on the face and
      arms were associated with teasing and bullying. The extent of vitiligo is
      associated with QOL impairment in children and adolescents, especially self
      consciousness, but also bullying and teasing. Different distributions of vitiligo
      lesions are associated with different aspects of QOL impairment. Teenagers ages
      15 to 17 years seem to experience the most self-consciousness of all pediatric
      age groups.

PMID- 24304126
TI  - Can you see it too? Observed and self-rated participation in mainstream schools
      in students with and without autism spectrum disorders.
AB  - OBJECTIVES: To examine the degree to which observations can capture perception of
      participation, observed and self-rated levels of interactions for students with
      and without autism spectrum disorders (ASD) were explored. METHODS: Frequencies
      and levels of involvement in interactions with classmates were observed and
      compared in 22 students with ASD and 84 of their classmates in mainstream
      schools, using a standardized protocol. Self-reported participation measurements
      regarding interactions with classmates and teachers from five questionnaire items
      were correlated with the observations. In total, 51,516 data points were coded
      and entered into the analyses, and correlated with 530 questionnaire ratings.
      RESULTS: Only one weak correlation was found in each group. Compared with
      classmates, students with ASD participated less frequently, but were not less
      involved when they actually did. CONCLUSIONS: Observations alone do not capture
      the individuals' perception of participation and are not sufficient if the
      subjective aspect of participation is to be measured.

PMID- 24304127
TI  - Double-layer electrode based on TiO2 nanotubes arrays for enhancing photovoltaic
      properties in dye-sensitized solar cells.
AB  - The present work reports a rapid and facile method to fabricate a novel double
      layer TiO2 photoanode, which is based on highly ordered TiO2 nanotube arrays and
      monodispersive scattering microspheres. This double-layer TiO2 sphere/TNTA
      photoanode have got many unique structural and optical properties from TiO2
      scattering microspheres, such as high specific surface area, multiple
      interparticle scattering, and efficient light-harvesting. Results indicate that
      this as-fabricated double-layer TiO2 sphere/TNTA front-illumination dye
      sensitized solar cell, which is fabricated from the TiO2 nanotube arrays with a
      17.4 MUm length after TiCl4 treatment, exhibits a pronounced power conversion
      efficiency of 7.24% under an AM1.5 G irradiation, which can be attributed to the
      increased incident photon-to-current conversion and light-harvesting efficiency.

PMID- 24304128
TI  - Point-to-axial chirality transfer--a new probe for "sensing" the absolute
      configurations of monoamines.
AB  - A host molecule, capable of freely adopting P or M helicity, is described for
      molecular recognition and chirality sensing. The host, consisting of a biphenol
      core, binds chiral amines via hydrogen-bonding interactions. The diastereomeric
      complex will favor either P or M helicity as a result of minimizing steric
      interactions of the guest molecule with the binding cavity of the host, resulting
      in a detectable exciton-coupled circular dichroic spectrum. A working model is
      proposed that enables non-empirical prediction of the chirality of the bound
      amine. 

PMID- 24304129
TI  - Stability and phylogenetic correlation in gut microbiota: lessons from ants and
      apes.
AB  - Correlation between gut microbiota and host phylogeny could reflect
      codiversification over shared evolutionary history or a selective environment
      that is more similar in related hosts. These alternatives imply substantial
      differences in the relationship between host and symbiont, but can they be
      distinguished based on patterns in the community data themselves? We explored
      patterns of phylogenetic correlation in the distribution of gut bacteria among
      species of turtle ants (genus Cephalotes), which host a dense gut microbial
      community. We used 16S rRNA pyrosequencing from 25 Cephalotes species to show
      that their gut community is remarkably stable, from the colony to the genus
      level. Despite this overall similarity, the existing differences among species'
      microbiota significantly correlated with host phylogeny. We introduced a novel
      analytical technique to test whether these phylogenetic correlations are derived
      from recent bacterial evolution, as would be expected in the case of
      codiversification, or from broader shifts more likely to reflect environmental
      filters imposed by factors such as diet or habitat. We also tested this technique
      on a published data set of ape microbiota, confirming earlier results while
      revealing previously undescribed patterns of phylogenetic correlation. Our
      results indicated a high degree of partner fidelity in the Cephalotes microbiota,
      suggesting that vertical transmission of the entire community could play an
      important role in the evolution and maintenance of the association. As additional
      comparative microbiota data become available, the techniques presented here can
      be used to explore trends in the evolution of host-associated microbial
      communities. 

PMID- 24304130
TI  - Surfactant-activated microgels: a new pathway to rheology modification.
AB  - Alkali swellable microgels are widely used to control rheology of formulated
      products containing surfactants. However, formulations based on these pH
      responsive polymers show undesirably large changes in yield stress in a range of
      pH close to the pKa of the acid group. Analysis of the behavior of a cross-linked
      copolymer of ethyl acrylate and methacrylic acid in the nonionized form (at pH
      below the pKa of methacrylic acid) in the presence of sodium dodecyl sulfate
      shows surfactant-mediated swelling (an increase in particle diameter by over
      2.5*) and a peak in zero-shear viscosity versus surfactant concentration
      indicating surfactant-mediated interaction of the swollen microgels. On the basis
      of these results, we demonstrate a new class of nonionic microgels composed of
      hydrophobic alkyl acrylates and hydrophilic hydroxyalkyl esters that utilize the
      effects of surfactant-mediated swelling and interaction to provide pH-independent
      rheological properties. 

PMID- 24304131
TI  - Prediction of partial nephrectomy outcomes by using the diameter-axis-polar
      nephrometry score.
AB  - OBJECTIVES: To evaluate the utility of diameter-axis-polar nephrometry score to
      evaluate partial nephrectomy outcomes. METHODS: Renal tumors of 127 patients with
      a functional contralateral kidney who underwent partial nephrectomy were scored
      using the diameter-axis-polar and R.E.N.A.L nephrometry scores. The mean tumor
      diameter was 2.9 cm (range 1.0-8.0 cm) and warm ischemic time was 27.3 min (range
      12-46 min). All patients underwent (99m)Tc- mercaptoacetyltriglycine renal
      scintigraphy preoperatively and 6 months postoperatively to assess effective
      renal plasma flow. We compared nephrometry scores with estimated glomerular
      filtration rate, effective renal plasma flow and ischemic time. RESULTS: The mean
      serum creatinine level was 0.84 mg/dL preoperatively and 0.93 mg/dL at 6 months
      postoperatively. The mean estimated glomerular filtration rate decreased from
      74.2 to 66.9 mL/min/1.73 m(2) . Effective renal plasma flow of the operated
      kidney decreased to 73.5% from baseline (from 157.0 to 114.3 mL/min/1.73 m(2)).
      Univariate and multivariate analyses showed that diameter-axis-polar score had a
      stronger association with the percent change in estimated glomerular filtration
      rate, effective renal plasma flow in the treated kidney and ischemia time
      compared with the R.E.N.A.L score. CONCLUSIONS: Diameter-axis-polar nephrometry
      score is a useful tool for the assessment of small renal tumors amenable to
      partial nephrectomy, and it better predicts postoperative functional changes and
      ischemic time compared with the R.E.N.A.L nephrometry score.

PMID- 24304132
TI  - Development and application of indicators for the reduction of potentially
      preventable hospital admissions related to medications.
AB  - OBJECTIVE: The Dutch HARM-Wrestling (HW) Task Force issued general and drug
      specific recommendations aimed at reducing hospital admissions related to
      medication (HARMs). This study examines if the drug-specific recommendations
      could be converted into indicators that could be monitored in existing databases
      of general practitioner (GP) or community pharmacy (CP) data. The study also
      assesses the performance of these indicators before and during the official
      release of HW recommendations. METHODS: HW recommendations were divided into sub
      recommendations. We studied to what extent these were measurable as indicators
      based on available information in both databases. For each measurable indicator,
      performance between 2007 and 2010 was determined and possibilities for further
      improvement were estimated. RESULTS: Thirty-four drug-specific HW recommendations
      were divided into 69 sub-recommendations, 32 of which were measurable as
      indicator in at least one of the databases. Application of these indicators
      between 2007 and 2010 showed that many of the indicators did not change over
      time. Possibilities for further improvement were estimated as moderate to major
      for 16/31 (52%) indicators measured in the GP database and 6/15 (40%) HW
      indicators measured in the CP database. CONCLUSIONS: Further implementation of
      the HW recommendations and development of additional monitoring methods are
      warranted to improve drug safety in outpatients.

PMID- 24304133
TI  - Local cholinergic interneurons modulate GABAergic inhibition in the chicken optic
      tectum.
AB  - The chicken optic tectum (TeO) and its mammalian counterpart, the superior
      colliculus, are important sensory integration centers. Multimodal information is
      represented in a topographic map, which plays a role in spatial attention and
      orientation movements. The TeO is organised in 15 layers with clear input and
      output regions, and further interconnected with the isthmic nuclei (NI), which
      modulate the response in a winner-takes-all fashion. While many studies have
      analysed tectal cell types and their modulation from the isthmic system
      physiologically, little is known about local network activity and its modulation
      in the tectum. We have recently shown with voltage-sensitive dye imaging that
      electrical stimulation of the retinorecipient layers results in a stereotypic
      response, which is under inhibitory control [S. Weigel & H. Luksch (2012) J.
      Neurophysiol., 107, 640-648]. Here, we analysed the contribution of acetylcholine
      (ACh) and the NI to evoked tectal responses using a pharmacological approach in a
      midbrain slice preparation. Application of the nicotinic ACh receptor (AChR)
      antagonist curarine increased the tectal response in amplitude, duration and
      lateral extent. This effect was similar but less pronounced when gamma
      aminobutyric acid(A) receptors were blocked, indicating interaction of inhibitory
      and cholinergic neurons. The muscarinic AChR antagonist atropine did not change
      the response pattern. Removal of the NI, which are thought to be the major source
      of cholinergic input to the TeO, reduced the response only slightly and did not
      result in a disinhibition. Based on the data presented here and the
      neuroanatomical literature of the avian TeO, we propose a model of the underlying
      local circuitry.

PMID- 24304134
TI  - Hepatic transcriptome profiling identifies differences in expression of genes
      associated with changes in metabolism and postnatal growth between Hereford and
      Holstein-Friesian bulls.
AB  - This study examined liver transcriptomic profiles of cattle distinctly different
      in meat and milk production capacity. It was performed on bulls of two different
      genetic backgrounds: Herefords (H), a meat breed, and Holstein-Friesians (HF), a
      dairy breed. Using bovine long oligo-microarrays and qPCR, we identified 128
      genes that are differentially expressed between the two breeds. In H bulls, we
      observed up-regulation of genes involved in fatty acid biosynthesis and lipid
      metabolism (CD36, CAT, HSD3B1, FABP1, ACAA1) and involved in insulin signaling
      (INSR, INSIG2, NR4A1) and down-regulation of genes involved in somatotropic axis
      signaling (IGF1, GHR, IGFBP3) as compared to HF. Transcriptome profiling of these
      two breeds allowed us to pinpoint the transcriptional differences between
      Holstein and Hereford bulls at hepatic level associated with changes in
      metabolism and postnatal growth. 

PMID- 24304135
TI  - Bradykinin B1 receptor-mediated vasodilation is impaired in myometrial arteries
      from women with pre-eclampsia.
AB  - OBJECTIVE: To investigate the vascular functional activity, localisation and
      expression of B1 and B2 kinin receptors in normal pregnancy and pre-eclampsia.
      METHODS: Kinin receptor-mediated relaxation of myometrial arteries was assessed
      using wire myography. Immunohistochemical staining and gene expression of kinin
      receptors in the myometrium was determined. RESULTS: B2 receptor-mediated
      relaxation was reduced in pre-eclampsia. B1 receptor-mediated relaxation was
      observed in a proportion of healthy women and was impaired in pre-eclampsia.
      Receptor expression and localisation was unaltered in pre-eclampsia. CONCLUSION:
      Here, we demonstrate a novel B1 receptor-mediated vasodilatation in healthy
      myometrial vessels that is absent in pre-eclampsia.

PMID- 24304136
TI  - Genetic variants of immunoglobulin gamma and kappa chains influence humoral
      immunity to the cancer-testis antigen XAGE-1b (GAGED2a) in patients with non
      small cell lung cancer.
AB  - GM (gamma marker) allotypes, genetic variants of immunoglobulin gamma chains,
      have been reported to be associated strongly with susceptibility to lung cancer,
      but the mechanism(s) underlying this association is not known. One mechanism
      could involve their contribution to humoral immunity to lung tumour-associated
      antigens. In this study, we aimed to determine whether particular GM and KM
      (kappa marker) allotypes were associated with antibody responsiveness to XAGE-1b,
      a highly immunogenic lung tumour-associated cancer-testis antigen. Sera from 89
      patients with non-small cell lung cancer (NSCLC) were allotyped for eight GM and
      two KM determinants and characterized for antibodies to a synthetic XAGE-1b
      protein. The distribution of various GM phenotypes was significantly different
      between XAGE-1b antibody-positive and -negative patients (P = 0.023), as well as
      in the subgroup of XAGE-1b antigen-positive advanced NSCLC (P = 0.007). None of
      the patients with the GM 1,17 21 phenotype was positive for the XAGE-1b antibody.
      In patients with antigen-positive advanced disease, the prevalence of GM 1,2,17
      21 was significantly higher in the antibody-positive group than in those who
      lacked the XAGE-1b antibody (P = 0.026). This phenotype also interacted with a
      particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were
      almost four times (odds ratio = 3.8) as likely to be positive for the XAGE-1b
      antibody as the subjects who lacked these phenotypes. This is the first report
      presenting evidence for the involvement of immunoglobulin allotypes in immunity
      to a cancer-testis antigen, which has important implications for XAGE-1b-based
      immunotherapeutic interventions in lung adenocarcinoma. 

PMID- 24304137
TI  - uPAR, IL-33, and ST2 values as a predictor of subclinical chorioamnionitis in
      preterm premature rupture of membranes.
AB  - Preterm premature rupture of membranes (PPROM) is defined as rupture of membrane
      that happens before the onset of labor and 37 weeks. Subclinical intrauterine
      infection is major etiological factor in the pathogenesis that increases
      mortality and morbidity associated with PPROM. This study was performed to
      evaluate the levels of maternal serum urokinase plasminogen activator receptor
      (uPAR), ST2 and interleukin (IL)-33 in PPROM and its relation with maternofetal
      infectious and morbidity. A total of 74 pregnant women, of which 49 with PPROM
      between 24 and 34 weeks gestation, and 25 normal pregnant women without PPROM
      were included in the study. Study group was seperated into 2 subgroups as PPROM
      and PPROM-histological chorioamnionitis (PPROM-HC). The blood samples were taken
      before the any medication. The mean serum IL-33, ST2, and uPAR values in the
      PPROM-HC group were significantly higher than PPROM and control group. The cut
      off values of IL-33, ST2, and uPAR were determined as 5.2, 2 and 6.4 ng/mL,
      respectively. A cut-off value of IL-33 of 5.2 ng/mL, the cut-off of ST2 of 2
      ng/mL and the cut-off of uPAR of 6.4 ng/mL showed similar sensitivity,
      specificity to IL-6 and the better sensitivity and specificity as compared to C
      reactive protein and total leucocyte count in predicting infection in PPROM. We
      evaluated the predictive value of uPAR, ST2 and IL-33 in PPROM and we concluded
      that all of them can be used as reliable biomarkers to determine infection
      without any clinical signs but it is necessary to be studied in different cohort
      groups and infectious diseases.

PMID- 24304140
TI  - The impact of self-awareness and depression on subjective reports of memory,
      quality-of-life and satisfaction with life following TBI.
AB  - OBJECTIVE: To determine the relationship between self-awareness and depressive
      symptomatology with self-reports of memory, Quality-of-Life (QoL) and
      satisfaction with life in individuals with traumatic brain injury (TBI). METHODS:
      Cross-sectional survey of 30 community dwelling adults, who sustained a TBI at
      least 1 year prior to study enrolment. Participants completed questionnaires to
      assess the constructs of depression, self-awareness, QoL, satisfaction with life
      and memory. RESULTS: Symptoms of depression were significantly associated with
      self-reports of poor memory abilities, lower QoL and lower satisfaction with
      life. Additionally, higher levels of self-awareness were associated with lower
      ratings of QoL and reduced memory abilities and better strategy use regarding
      memory. However, when examining the contribution of each construct individually,
      depressive symptomatology, and not self-awareness, was significantly associated
      with subjective self-reports of memory, QoL and satisfaction with life.
      CONCLUSIONS: This pattern of relationships illustrates that, when a person has a
      low level of depressive symptoms, his/her reports of QoL, memory and satisfaction
      with life will be more positive; however, he/she will demonstrate more difficulty
      with self-awareness. Thus, psychological aspects of recovery must, therefore, be
      taken into account when using self-reported measures in the evaluation of persons
      who have sustained TBI.

PMID- 24304141
TI  - Competency-based project to review community/public health curricula.
AB  - Changes in the delivery of community/public health (C/PH) nursing have challenged
      nursing educators to seek innovative ways to ensure that their educational
      programs produce competent entry-level practitioners. This article describes how
      public health professionals and faculty from eight regional colleges and
      universities in Southeastern Wisconsin came together to better understand both
      what C/PH nursing content was being taught in the region, and the extent to which
      that content was aligned with the Public Health Nurse Competencies defined by the
      Quad Council in 2004. Based on self-reporting by nursing school faculty as well
      as a separate mapping of course objectives into the competency areas, the project
      found that the curricula of the participating colleges and universities
      adequately addressed most of the competencies in the Quad Council domains one
      through six. Competencies in domains seven (financial planning/management skills)
      and eight (leadership/systems thinking skills) were not, however, adequately
      addressed and plans were subsequently developed to fill those gaps. In addition
      to helping each institution identify strengths and gaps in its own curriculum,
      the project provided an unprecedented opportunity for both public health
      professionals and academics to build relationships, share best practices, and
      exchange resources.

PMID- 24304142
TI  - Factors involved in the development of diaper-area granuloma of the aged.
AB  - An infant skin disease with clusters of nodules in the diaper contact area was
      reported as granuloma gluteale infantum. Recently, the number of elderly patients
      with this condition has increased, and it has been reported as diaper-area
      granuloma of the aged. These lesions are presumably caused by irritation from
      feces and urine. We observed similar cutaneous symptoms in six elderly patients,
      five of whom revealed clusters of nodules arranged in a circular pattern in the
      gluteal region presenting a peculiar clinical picture. They were all bedridden
      and wore cloth diapers. We speculate that wearing a cloth diaper seems to be a
      major factor behind this condition. Another factor was sitting during the day. A
      subject had lesions with nodules on the scrotum. The distribution of nodules
      appeared to be related to the body position and vigorous movement of the patient.
      In all cases, topical steroid therapies were not effective. They were all
      positive for bacteriuria. Chronic urinary tract infection further irritates the
      skin. It is necessary to reduce urine contact and keep the lesion clean. 

PMID- 24304139
TI  - Comparative analysis of gingival tissue antigen presentation pathways in ageing
      and periodontitis.
AB  - AIM: Gingival tissues of periodontitis lesions contribute to local elevations in
      mediators, including both specific T cell and antibody immune responses to oral
      bacterial antigens. Thus, antigen processing and presentation activities must
      exist in these tissues to link antigen-presenting cells with adaptive immunity.
      We hypothesized that alterations in the transcriptome of antigen processing and
      presentation genes occur in ageing gingival tissues and that periodontitis
      enhances these differences reflecting tissues less capable of immune resistance
      to oral pathogens. MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23
      years of age were examined. A buccal gingival sample from healthy or
      periodontitis sites was obtained, total RNA isolated, and microarray analysis was
      used to describe the transcriptome. RESULTS: The results demonstrated increased
      transcription of genes related to the MHC class II and negative regulation of NK
      cells with ageing in healthy gingival tissues. In contrast, both adult and ageing
      periodontitis tissues showed decreased transcription of genes for MHC class II
      antigens, coincident with up-regulation of MHC class I-associated genes.
      CONCLUSION: These transcriptional changes suggest a response of healthy ageing
      tissues through the class II pathway (i.e. endocytosed antigens) and altered
      responses in periodontitis that could reflect host-associated self-antigens or
      targeting cytosolic intracellular microbial pathogens.

PMID- 24304143
TI  - A case of maxillary sarcoma in a chimpanzee (Pan troglodytes).
AB  - Oral malignancy is rare in chimpanzees. A 34-year-old female chimpanzee (Pan
      troglodytes) at Kumamoto Sanctuary, Japan, had developed it. Treatment is
      technically difficult for chimpanzees while malignant neoplasm is seemingly
      rising in captive populations. Widespread expert discussion, guidelines for
      treatment, especially for great apes in terminal stages is urgently needed. 

PMID- 24304144
TI  - Organophosphates as solvents for electrolytes in electrochemical devices.
AB  - A homologous series of fire-retardant oligoalkyleneoxy-phosphates was synthesized
      for evaluation as liquid or gel-type electrolyte media for dye-sensitized solar
      cells (DSSCs) and secondary lithium batteries. Unoptimized DSSC electrolyte
      formulations for DSSCs achieved ionic conductivities as high as 5.71 * 10(-3) S .
      cm(-1) and DSSC test-cell efficiencies up to 3.6% as well as Voc, Jsc, and ff up
      to 0.81 V, 8.03 mA . cm(-2), and 0.69, respectively. Poly(bis-(2-(2
      methoxyethoxy)ethoxy)phosphazene)-based Li(+)-conducting gel electrolytes
      plasticized with the best performing phosphate had conductivities as high as 9.9
      * 10(-4) S . cm(-1) at 30  degrees C. All the liquids have boiling points higher
      than 197  degrees C. The results show that the viscosity, glass transition
      temperatures, and conductivity of the phosphates are dependent mainly on the
      length of the longest alkyleneoxy chain.

PMID- 24304145
TI  - The Child and Adolescent Scale of Environment (CASE): Further validation with
      youth who have chronic conditions.
AB  - OBJECTIVE: To further validate the Child and Adolescent Scale of Environment
      (CASE). METHODS: Baseline data (n = 430) were analyzed from a longitudinal study
      on quality of life for youth with chronic conditions ages 11-17 in Ontario,
      Canada. Internal consistency and structure, and convergent and discriminant
      validity were examined via Cronbach's alpha (alpha), exploratory factor analyses,
      correlation analyses and ANOVA. RESULTS: The CASE had high internal consistency
      (alpha = 0.89). A three-factor solution was produced with 55% variance explained:
      (1) Community/Home Resources, (2) School Resources and (3) Physical
      Design/Access). CASE total and factor scores were significantly correlated with
      scores from measures of impairment and participation (i.e. youth with more
      problematic environments had more severe impairment and more restricted
      participation). Significant differences in CASE scores existed for primary
      condition and impairment severity, but not for age or gender. CONCLUSION: Results
      provide additional CASE validation evidence. Further testing is needed with more
      diverse and representative samples.

PMID- 24304146
TI  - The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic
      stroke.
AB  - There is a continuous urgent need to explore the pathogenesis and biochemical
      changes within the infarcted area during acute ischemic stroke (IS). Matrix
      metalloproteinases (MMPs), prevailing extracellular endopeptideses, can digest
      proteins located extracellulary, e.g. collagen, proteoglycans, elastin or
      fibronectin. Among MMPs, gelatinases (MMP-2 and MMP-9) are the most investigated
      enzymes. Gelatinases possess the ability to active numerous pro-inflammatory
      agents as chemokine CXCL-8, interleukin 1beta or tumor necrosis factor alpha.
      Moreover, due to digestion of collagen type IV (the component of basal membranes)
      and tight junction proteins (TJPs) they facilitate to cross the endothelium by
      leukocytes. Due to the significant role of gelatinases during brain ischemia,
      their selective inhibition seems to be an interesting kind of treatment of acute
      stroke. The synthetic inhibitors of gelatineses decrease the infarct volume in
      animal models of IS. In clinical practice statins, the lipid-lowering drugs
      possess the ability to inhibit the activity of MMP-9 during acute IS. This review
      briefly provides the most important information about the involvement of MMP-2
      and MMP-9 in the pathogenesis of brain ischemia. 

PMID- 24304147
TI  - Metabolism and clinical pharmacokinetics of 2-methyl-n-(2'-(pyrrolidinyl-1
      ylsulfonyl)-n-[1,1'-biphenyl]-4-yl)propran-1-amine: insights into monoamine
      oxidase- and CYP-mediated disposition by integration of in vitro ADME tools.
AB  - 1. In early discovery stages, 2-methyl-N-(2'-(pyrrolidinyl-1-ylsulfonyl)-[1,1'
      biphenyl]-4-yl)propan-1-amine (PBPA) demonstrated monoamine oxidase A (MAO-A) and
      cytochrome P450 (CYP)-mediated clearance. While human liver microsomes predicted
      low CL(b) PBPA demonstrated a moderate CL(p)/F in humans. The plasma
      pharmacokinetic (PK) of PBPA was characterized by unexpected high inter
      individual variability. Hence, a retrospective analysis was undertaken to
      understand the disposition processes of PBPA, by applying in vitro mechanistic
      tools. 2. The in vitro-to-in vivo of rat CL(b) of PBPA was calculated as similar
      to that of human, suggesting rat to be a better predictor of a MAO-A/CYP
      substrate, but not dog or monkey; this is consistent with differences in
      expression of MAO-A in rat, dog, monkey and human. Fraction metabolized (f(m)) of
      human MAO A (hMAO-A) (50%), CYP3A4 (8%), CYP3A5 (16%) and CYP2D6 (29%) was
      determined, in vitro. 3. While the fm of CYP3A5 was <50%, Michaelis-Menten
      kinetics demonstrated that it was a higher capacity pathway compared with MAO-A,
      2D6 and 3A4. This was consistent with strong association of dose-normalized
      plasma C(max) and area under the plasma concentration time curve (AUC(0-tlast))
      of PBPA with CYP3A5 genotype, but not with genotype of CYP2D6. 4. This
      investigation demonstrates the value of integrating in vitro mechanistic tools to
      gain comprehensive understanding of disposition properties of drug candidates, in
      a discovery paradigm and prior to the investment in clinical trials.

PMID- 24304148
TI  - Synthetic endeavors toward 2-nitro-4-alkylpyrroles in the context of the total
      synthesis of heronapyrrole C and preparation of a carboxylate natural product
      analogue.
AB  - The synthesis of 2-nitro-4-oligoprenyl-substituted pyrrole derivatives relevant
      to the heronapyrroles and related natural products was investigated. Among
      numerous approaches, nitration of a 3-farnesyl-substituted unprotected pyrrole
      using AcONO2 gave the best results, albeit still with unsatisfactory yield and
      regioselectivity. Therefore, the synthesis of (-)-heronapyrrole C acid, an
      analogue of the naturally occurring antibiotic heronapyrrole C carrying a
      bioisosteric carboxylate in place of the nitro group, was examined. In lieu of
      the unsatisfactory nitration, a regioselective acylation with Cl3CCOCl was
      carried out (>8:1 regioselectivity, in contrast to the 1:1.3 ratio for the
      nitration). The trichloromethyl ketone was converted to the desired acid in a
      haloform reaction at the final stage of the synthesis. Further key steps of the
      analogue synthesis involved a position- and stereoselective Corey-Noe-Lin
      dihydroxylation and an organocatalytic double Shi epoxidation. A biomimetic
      polyepoxide cyclization cascade established the bis-THF backbone. Thus, (-)
      heronapyrrole C acid was synthesized in eight steps (14.5% overall yield) from
      commercially available starting materials. 

PMID- 24304149
TI  - Comparison of peptide nucleic acid fluorescence in situ hybridization assays with
      culture-based matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry for the identification of bacteria and yeasts from blood cultures
      and cerebrospinal fluid cultures.
AB  - Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a molecular
      diagnostic tool for the rapid detection of pathogens directly from liquid media.
      The aim of this study was to prospectively evaluate PNA FISH assays in comparison
      with culture-based matrix-assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF MS) identification, as a reference method, for both
      blood and cerebrospinal fluid (CSF) cultures, during a 1-year investigation. On
      the basis of the Gram stain microscopy results, four different PNA FISH
      commercially available assays were used ('Staphylococcus aureus/CNS',
      'Enterococcus faecalis/OE', 'GNR Traffic Light' and 'Yeasts Traffic Light' PNA
      FISH assays, AdvanDx). The four PNA FISH assays were applied to 956 positive
      blood cultures (921 for bacteria and 35 for yeasts) and 11 CSF cultures. Among
      the 921 blood samples positive for bacteria, PNA FISH gave concordant results
      with MALDI-TOF MS in 908/921 (98.64%) samples, showing an agreement of 99.4% in
      the case of monomicrobial infections. As regards yeasts, the PNA FISH assay
      showed a 100% agreement with the result obtained by MALDI-TOF MS. When PNA FISH
      assays were tested on the 11 CSF cultures, the results agreed with the reference
      method in all cases (100%). PNA FISH assays provided species identification at
      least one work-day before the MALDI-TOF MS culture-based identification. PNA FISH
      assays showed an excellent efficacy in the prompt identification of main
      pathogens, yielding a significant reduction in reporting time and leading to more
      appropriate patient management and therapy in cases of sepsis and severe
      infections. 

PMID- 24304151
TI  - pH-responsive lanthanide complexes based on reversible ligation of a
      diphenylphosphinamide.
AB  - Ln-dpp-DO3A-based complexes [dpp is a pendant diphenylphosphinamide moiety and
      DO3A is 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane] exhibit pH
      responsive reversible ligation of the phosphinamide for both the gadolinium(III)
      and europium(III) analogues. pKa values were 8.1 (+/-0.1) and 7.8 (+/-0.1) for
      Gd.1 and Gd.2, respectively. The relaxivities (20 MHz, 298 K) of the
      gadolinium(III) analogues were r1 = 7.9 mM(-1) s(-1) (Gd.1) and r1 = 8.2 mM(-1)
      s(-1) (Gd.2) in acidic media, corresponding to a hydration state q = 2; in basic
      media, deprotonation and coordination of the phosphinamide occurs, with r1 = 5.4
      mM(-1) s(-1) (Gd.1) and r1 = 4.4 mM(-1) s(-1) (Gd.2) corresponding to q = 1.
      Sensitized luminescent emission was observed from the europium(III) analogues
      following excitation at lambdaex = 270 nm. The hydration state values of the
      europium(III) analogues were consistent with those of the gadolinium(III)
      complexes, i.e., q = 1 and 2 in basic and acidic media, respectively. The ratio
      of the emission intensities of the DeltaJ = 1 and 2 bands enables concentration
      independent reporting of the pH. Excited-state pKa values were 8.3 (+/-0.1) and
      8.5 (+/-0.1) for Eu.1 and Eu.2, respectively. 

PMID- 24304150
TI  - Two analogues of fenarimol show curative activity in an experimental model of
      Chagas disease.
AB  - Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is
      an increasing threat to global health. Available medicines were introduced over
      40 years ago, have undesirable side effects, and give equivocal results of cure
      in the chronic stage of the disease. We report the development of two compounds,
      6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established
      T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10
      mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are
      noncytotoxic, show no adverse effects in vivo following repeat dosing, are
      prepared by a short synthetic route, and have druglike properties suitable for
      preclinical development. 

PMID- 24304152
TI  - Asymmetric substitution at the tetrasubstituted chiral carbon: catalytic ring
      opening alkylation of racemic 2,2-disubstituted aziridines with 3-substituted
      oxindoles.
AB  - A highly diastereo- and enantioselective ring-opening alkylation of racemic 2,2
      disubstituted aziridines with 3-substituted oxindoles is achieved under the
      catalysis of a chiral 1,2,3-triazolium salt. This reaction represents a hitherto
      unknown, catalytic stereoselective carbon-carbon bond formation through direct
      substitution at the tetrasubstituted chiral carbon. 

PMID- 24304153
TI  - Changes in copper and zinc serum levels in women wearing a copper TCu-380A
      intrauterine device.
AB  - OBJECTIVE To assess the effects of the copper intrauterine device (IUD) TCu-380A,
      on copper and zinc serum levels. MATERIAL AND METHODS This longitudinal study
      enrolled 121 women attending Health Centres in Tehran between November 2011 and
      August 2012. A blood sample was obtained before use and three months after
      insertion of a TCu-380A IUD. Serum levels of copper and zinc were measured for
      the 101 women who had completed three months with the device in situ. Analyses of
      change included paired t-tests, McNemar tests and linear regression. RESULTS
      Significant elevations in mean serum levels were found for both copper (170.22
      MUg/dl at three months vs.160.40 MUg/dl at baseline, p = 0.034) and zinc (107.67
      MUg/dl at three months vs. 94.61 MUg/dl at baseline, p < 0.001) three months
      after IUD insertion. CONCLUSIONS A slight, but significant increase in copper
      serum levels, not reaching toxic levels, was observed three months after TCu-380A
      IUD insertion. Zinc levels too had risen significantly, which was quite
      unexpected, and warrants further investigation.

PMID- 24304154
TI  - Comparison of 90-day complications between ileal conduit and neobladder
      reconstruction after radical cystectomy: a retrospective multi-institutional
      study in Japan.
AB  - OBJECTIVE: To determine the differences in the type, incidence, and severity of
      90-day morbidity after radical cystectomy between two different methods of
      urinary diversion, ileal conduit and neobladder. METHODS: We carried out a
      retrospective multi-institutional study by reviewing the records of 668 patients
      treated with open radical cystectomy, and ileal conduit (n = 493) or neobladder
      substitution (n = 175) between 1997 and 2010. All complications within 90 days
      after surgery were divided into 11 specific categories as reported by the
      Memorial-Sloan Kettering Cancer Center, and graded according to the modified
      Clavien system. Type, incidence and severity of the 90-day morbidity between the
      two different types of urinary diversions were compared. RESULTS: There was no
      significant difference in the overall complication rates between the two groups
      (ileal conduit: 72% [353/493], neobladder: 74% [129/175], P = 0.5909), whereas
      the neobladder group had fewer major (grade 3 or more) complications (13 vs 20%,
      respectively, P = 0.0271). The neobladder group had more infectious complications
      (43 vs 31%, respectively, P = 0.0037), mainly as a result of urinary tract
      infection, whereas the ileal conduit group had more wound-related complications
      (24 vs 14%, respectively, P = 0.0068), mainly as a result of surgical site
      infection. The 90-day mortality rates were 1.1% (2/175) in the neobladder group
      and 1.6% (8/493) in the ileal conduit group (P = 0.6441). CONCLUSIONS: There was
      no significant difference in the overall complication rates between the two
      methods, and patients with neobladder had fewer major complications. The
      neobladder group had more infectious complications, whereas the ileal conduit
      group had more wound-related complications.

PMID- 24304155
TI  - Calculations of the electric fields in liquid solutions.
AB  - The electric field created by a condensed-phase environment is a powerful and
      convenient descriptor for intermolecular interactions. Not only does it provide a
      unifying language to compare many different types of interactions, but it also
      possesses clear connections to experimental observables, such as vibrational
      Stark effects. We calculate here the electric fields experienced by a vibrational
      chromophore (the carbonyl group of acetophenone) in an array of solvents of
      diverse polarities using molecular dynamics simulations with the AMOEBA
      polarizable force field. The mean and variance of the calculated electric fields
      correlate well with solvent-induced frequency shifts and band broadening,
      suggesting Stark effects as the underlying mechanism of these key solution-phase
      spectral effects. Compared to fixed-charge and continuum models, AMOEBA was the
      only model examined that could describe nonpolar, polar, and hydrogen bonding
      environments in a consistent fashion. Nevertheless, we found that fixed-charge
      force fields and continuum models were able to replicate some results of the
      polarizable simulations accurately, allowing us to clearly identify which
      properties and situations require explicit polarization and/or atomistic
      representations to be modeled properly, and to identify for which properties and
      situations simpler models are sufficient. We also discuss the ramifications of
      these results for modeling electrostatics in complex environments, such as
      proteins. 

PMID- 24304156
TI  - Putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme
      g are involved in the early immune response of brown-marbled grouper, Epinephelus
      fuscoguttatus, Forskal, to Vibrio alginolyticus.
AB  - The gram-negative bacterium, Vibrio alginolyticus, has frequently been identified
      as the pathogen responsible for the infectious disease called vibriosis. This
      disease is one of the major challenges facing brown-marbled grouper aquaculture,
      causing fish farmers globally to suffer substantial economic losses. The
      objective of this study was to investigate the proteins involved in the immune
      response of brown-marbled grouper fingerlings during their initial encounter with
      pathogenic organisms. To achieve this objective, a challenge experiment was
      performed, in which healthy brown-marbled grouper fingerlings were divided into
      two groups. Fish in the treated group were subjected to intraperitoneal injection
      with an infectious dose of V. alginolyticus suspended in phosphate-buffered
      saline (PBS), and those in the control group were injected with an equal volume
      of PBS. Blood samples were collected from a replicate number of fish from both
      groups at 4 h post-challenge and analysed for immune response-related serum
      proteins via two-dimensional gel electrophoresis. The results showed that 14
      protein spots were altered between the treated and control groups; these protein
      spots were further analysed to determine the identity of each protein via MALDI
      TOF/TOF. Among the altered proteins, three were clearly overexpressed in the
      treated group compared with the control; these were identified as putative
      apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g. Based
      on these results, these three highly expressed proteins participate in immune
      response-related reactions during the initial exposure (4 h) of brown-marbled
      grouper fingerling to V. alginolyticus infection.

PMID- 24304157
TI  - The mis-measure of physician performance.
AB  - The Affordable Care Act directs the Secretary of Health and Human Services to
      compare individual physicians using patient experience measures. This policy
      initiative will utilize the Clinician and Group Consumer Assessment of Healthcare
      Providers and Systems (CG-CAHPS) survey program. It will impact over 700,000
      eligible physicians and will be tied to reimbursement and the Centers for
      Medicare and Medicaid Services' Physician Compare reporting feature starting in
      2015. We believe that the relevance of this framework to today's clinical
      environment is a critical issue to address before implementing this regulatory
      mandate. In this article we discuss our concerns about tying individual physician
      performance to CG-CAHPS scores, including: 1) intrinsic versus extrinsic
      approaches to assessing the patient experience, 2) measurement issues, and 3)
      unintended consequences. We also suggest an alternative pathway and opt-out
      mechanism to facilitate more rapid translation of service excellence into
      clinical practice. 

PMID- 24304158
TI  - Dispensing channel and medication adherence: evidence across 3 therapy classes.
AB  - OBJECTIVES: To examine the association of mail order versus retail pharmacy
      dispensing channels with medication adherence for patients on diabetes,
      hypertension, or high blood cholesterol medications, controlling for prior
      adherence behavior (PAB) and days of supply. STUDY DESIGN: Retrospective analysis
      using de-identified pharmacy claims data from a large national pharmacy benefits
      manager between April 2009 and December 2011. METHODS: Continuously eligible
      patients with an antidiabetic, antihypertensive, or antihyperlipidemic
      prescription claim between October and December 2009 were identified and followed
      over a 2-year period. Multivariate logistic regression was used to evaluate the
      impact of dispensing channel on medication adherence, controlling for differences
      in demographics, disease burden, and drug use pattern. Patients with a medication
      possession ratio of 80% or greater were considered adherent. The analysis
      controlled for PAB by using patients' adherence status in 2010. RESULTS: Overall,
      patients using the mail order channel had higher adherence rates than their
      retail counterparts across all 3 therapeutic classes. In 2011, the likelihood of
      a mail order patient being adherent was approximately 1.15 times higher than that
      of a retail patient for antidiabetics, 1.11 times higher for antihypertensives,
      and 1.19 times higher for antihyperlipidemics. PAB was the strongest contributor
      to the odds of a patient being adherent across all 3 therapy classes: odds ratios
      ranged from 5.87 to 9.49. CONCLUSIONS: After adjusting for PAB, differential days
      of supply, and differences in demographics and disease burden, patients who use
      mail order have a greater likelihood of being adherent than patients who use a
      retail pharmacy.

PMID- 24304159
TI  - Utilization of lymph node dissection, race/ethnicity, and breast cancer outcomes.
AB  - OBJECTIVES: Although large differences by race/ethnicity in breast cancer
      survival are well established, it is unknown whether disparities in nodal surgery
      utilization explain the racial/ethnic disparities in survival among women with
      micrometastasis and macrometastasis in sentinel lymph nodes (SLNs). STUDY DESIGN:
      Retrospective cohort study. METHODS: Women with breast cancer who underwent
      sentinel lymph node biopsy (SLNB) and who were found to have nodal metastases
      were identified from the Surveillance, Epidemiology, and End Results database
      (1998-2005). Outcomes data were examined for patients who underwent SLNB alone
      versus SLNB with axillary lymph node dissection (ALND). RESULTS: Proportions of
      patients receiving SLNB alone or receiving SLNB with a complete ALND were not
      statistically different among women of different racial/ethnic backgrounds (P =
      .8). Patients of African American descent or Hispanic origin had reduced overall
      survival, whereas patients of Hispanic origin had reduced diseasespecific
      survival after adjusting for selected covariates. Adjusting for nodal surgery did
      not reduce racial/ethnic disparities in overall survival or disease-specific
      survival. CONCLUSIONS: The disparities in survival among African American and
      Hispanic women with breast cancer are not explained by nodal surgery utilization
      among women with micrometastasis and macrometastasis in SLNs.

PMID- 24304160
TI  - Inefficiencies in osteoarthritis and chronic low back pain management.
AB  - OBJECTIVE: To identify inefficiencies in drug and medical service utilization
      related to pain management in patients with osteoarthritis and chronic low back
      pain. STUDY DESIGN: This retrospective cohort study applied revised measures of
      pain management inefficiencies to Humana Medicare members with osteoarthritis
      and/or chronic low back pain. METHODS: Subjects had either 2 or more claims for
      osteoarthritis on different days or 2 or more claims for low back pain 90 or more
      days apart, from January 1, 2008, to June 30, 2010, with the first occurrence
      assigned the index date. Inefficiencies were identified for 365 days
      postindex.Pain-related healthcare costs postindex were compared between members
      with and without inefficiencies. A generalized linear model calculated adjusted
      costs per member controlling for age, sex, and comorbidities. RESULTS: Most
      members diagnosed with osteoarthritis, chronic low back pain, or both (N =
      68,453) had at least 1 inefficiency measure (n = 37,863) during the postindex
      period. High per member costs were for repeated surgical procedures ($26,451) and
      inpatient admissions ($19,372) compared with members without inefficiencies
      ($781; P < .0001). High total costs (prevalence times per member cost) were for
      repeated diagnostic testing and excessive office visits. Members with an
      inefficiency had adjusted pain-related costs 5.42 times higher than those of
      members without an inefficiency (P <.0001). CONCLUSIONS: Pain management
      inefficiencies are common and costly among Humana Medicare members with
      osteoarthritis and/or chronic low back pain. Further work by providers and payers
      is needed to determine benefits of member identification and early intervention
      for these inefficiencies.

PMID- 24304161
TI  - Empirical analysis of domestic medical travel for elective cardiovascular
      procedures.
AB  - OBJECTIVES: To investigate whether domestic medical travel (DMT; traveling
      outside of one's home region but within the United States for medical care) and
      surgeon volume affect clinical outcomes and costs for patients undergoing
      elective cardiovascular procedures. STUDY DESIGN: Retrospective, cross-sectional
      analysis of patient discharge data from US academic medical centers. METHODS:
      Patients were classified as medical travelers if they received elective,
      nonemergent care more than 250 miles from home. High-volume surgeons (HVSs) were
      those above the 75th percentile compared with other study surgeons in the annual
      number of cardiovascular surgeries performed. Multivariable regression models
      were fit to test the relationships among complications, mortality, length of stay
      (LOS), cost, DMT status, and surgeon volume, controlling for sociodemographic and
      clinical factors. RESULTS: Patients who traveled to HVSs were more likely to be
      male, white, have lower severity of illness, and have health insurance through an
      indemnity plan or preferred provider organization with coverage outside of the
      patient's home region. Patients who traveled to HVSs had shorter LOS and fewer
      complications than those who received care from local, low-volume surgeons. There
      was no significant difference in mortality between travelers and nontravelers.
      CONCLUSIONS: Patients who travelled to HVSs for elective cardiovascular
      procedures had outcomes similar to or better than those of patients who received
      care locally from low-volume surgeons. We found no increase in complications or
      LOS, despite potentially complex logistical arrangements required by travelers.
      More work is needed to evaluate the potential of DMT to improve the value of care
      provided for selected procedures.

PMID- 24304162
TI  - Physician capability to electronically exchange clinical information, 2011.
AB  - OBJECTIVES: To provide national estimates of physician capability to
      electronically share clinical information with other providers and to describe
      variation in exchange capability across states and electronic health record (EHR)
      vendors using the 2011 National Ambulatory Medical Care Survey Electronic Medical
      Record Supplement. STUDY DESIGN: Survey of a nationally representative sample of
      nonfederal office-based physicians who provide direct patient care. METHODS: The
      survey was administered by mail with telephone follow-up and had a 61% weighted
      response rate. The overall sample consisted of 4326 respondents. We calculated
      estimates of electronic exchange capability at the national and state levels, and
      applied multivariate analyses to examine the association between the capability
      to exchange different types of clinical information and physician and practice
      characteristics. RESULTS: In 2011, 55% of physicians had computerized capability
      to send prescriptions electronically; 67% had the capability to view lab results
      electronically; 42% were able to incorporate lab results into their EHR; 35% were
      able to send lab orders electronically; and, 31% exchanged patient clinical
      summaries with other providers. The strongest predictor of exchange capability is
      adoption of an EHR. However, substantial variation exists across geography and
      EHR vendors in exchange capability, especially electronic exchange of clinical
      summaries. CONCLUSIONS: In 2011, a majority of office-based physicians could
      exchange lab and medication data, and approximately one-third could exchange
      clinical summaries with patients or other providers. EHRs serve as a key
      mechanism by which physicians can exchange clinical data, though physicians'
      capability to exchange varies by vendor and by state.

PMID- 24304163
TI  - The effects of ageing on the onset and disappearance of unexplained abdominal
      pain: a population-based study.
AB  - BACKGROUND: The population >=65 years is rapidly increasing, but remarkably
      little is known about the natural history of abdominal pain with ageing. AIM: To
      prospectively evaluate the natural history of abdominal pain (severity and
      frequency) in a US population, and evaluate potential risk factors (including
      somatisation) for the onset and disappearance of abdominal pain with increasing
      age. METHODS: Between 1988 and 2004, valid self-report questionnaires that
      recorded gastrointestinal symptoms including severity and frequency of abdominal
      pain were mailed to randomly selected cohorts of community residents followed
      over time. This study identified all respondents who answered abdominal pain
      questions at an initial and follow-up survey. RESULTS: One thousand nine hundred
      and thirteen subjects were included (mean age in years at first survey: 48 +/- 12
      (SD), mean age at second survey: 59 +/- 13 (SD); 53% female). The onset and
      disappearance rate of abdominal pain over the follow-up were 18% (95% CI, 16, 20)
      and 47% (43, 50) respectively. The rates of increasing vs. decreasing abdominal
      pain score were 18% (16, 20) vs. 21% (20, 23) respectively. While younger age at
      initial survey was associated with the onset of abdominal pain {vs. subjects
      without abdominal pain, [OR 0.9 (0.7, 1.0)]}, older age at initial survey and
      times between surveys were associated with the disappearance of abdominal pain
      {vs. subjects with abdominal pain, [OR 1.2 (1.0, 1.5)]}. Female gender (OR 1.4
      [1.0, 2.1]), higher somatisation scores (OR 5.3 [3.2, 8.7]) and larger changes in
      somatisation score (OR 2.1 [1.4, 3.2]) were positively associated with the onset
      of abdominal pain. CONCLUSION: Increasing age is associated with the
      disappearance of abdominal pain in the community.

PMID- 24304164
TI  - First trimester maternal characteristics, Doppler parameters and serum analytes
      after preeclampsia.
AB  - OBJECTIVE: To evaluate the impact of prior preeclampsia on first trimester
      assessment in subsequent pregnancy. METHODS: A total of 1283 parous patients were
      prospectively enrolled at 9-14 weeks of gestation. Maternal biophysical
      characteristics, ultrasound parameters and placental analytes were compared
      between women with and without prior preeclampsia. RESULTS: There is no
      association between prior preeclampsia and the first trimester ultrasound
      parameters or placental analytes studied. The effects of prior preeclampsia in
      subsequent pregnancy are exaggerated by increasing parity and are predominantly
      blood pressure-related, independent of other cardiovascular risk factors.
      CONCLUSION: There is a potential role for lifestyle modification and stricter
      pregnancy blood pressure control in patients with prior preeclampsia.

PMID- 24304166
TI  - Long residence time inhibition of EZH2 in activated polycomb repressive complex
      2.
AB  - EZH2/PRC2 catalyzes transcriptionally repressive methylation at lysine 27 of
      histone H3 and has been associated with numerous cancer types. Point mutations in
      EZH2 at Tyr641 and Ala677 identified in non-Hodgkin lymphomas alter substrate
      specificity and result in increased trimethylation at histone H3K27.
      Interestingly, EZH2/PRC2 is activated by binding H3K27me3 marks on histones, and
      this activation is proposed as a mechanism for self-propagation of gene
      silencing. Recent work has identified GSK126 as a potent, selective, SAM
      competitive inhibitor of EZH2 capable of globally decreasing H3K27 trimethylation
      in cells. Here we show that activation of PRC2 by an H3 peptide trimethylated at
      K27 is primarily an effect on the rate-limiting step (kcat) with no effect on
      substrate binding (Km). Additionally, GSK126 is shown to have a significantly
      longer residence time of inhibition on the activated form of EZH2/PRC2 as
      compared to unactivated EZH2/PRC2. Overall inhibition constant (Ki*) values for
      GSK126 were determined to be as low as 93 pM and appear to be driven by slow
      dissociation of inhibitor from the activated enzyme. The data suggest that
      activation of EZH2 allows the enzyme to adopt a conformation that possesses
      greater affinity for GSK126. The long residence time of GSK126 may be beneficial
      in vivo and may result in durable target inhibition after drug systemic
      clearance. 

PMID- 24304167
TI  - Prognostic value of treadmill stress echocardiography at extremes of exercise
      performance: submaximal <85% maximum predicted heart rate versus high exercise
      capacity >= 10 metabolic equivalents.
AB  - BACKGROUND: Submaximal stress testing or achieving <85% maximum predicted heart
      rate (MPHR) may lead to nondiagnostic results and indeterminate outcomes. High
      exercise capacity (>= 10 metabolic equivalents, METS) is a predictor of favorable
      prognosis. The purpose of this study was to evaluate the prognostic value of
      submaximal or high exercise capacity stress echocardiography. METHODS: We
      evaluated 1781 patients (55 +/- 13 years; 59% male) undergoing treadmill stress
      echocardiography divided into 811 patients with submaximal (<85% MPHR) and 970
      patients with high exercise capacity (>= 10 METS). Resting left ventricular
      ejection fraction and regional wall motion were assessed. The left ventricle was
      divided into 16 segments and scored on 5-point scale of wall motion. Abnormal
      stress echocardiography was defined as stress-induced ischemia (wall-motion score
      of >= 1 grade). Follow-up (3.3 +/- 1.5 years) for nonfatal myocardial infarction
      (MI) (n = 40) and cardiac death (n = 52) were obtained. RESULTS: By univariate
      analysis, echocardiographic variables of ejection fraction, peak wall-motion
      score index (WMSI) and number of new ischemic wall-motion abnormalities were
      significant predictors of cardiac events. Cumulative survival was significantly
      worse in patients with abnormal (ischemic) versus normal (nonischemic) stress
      echocardiography in submaximal (4.4%/year vs. 1.3%/year, P < 0.0001) and high
      exercise capacity (1.5%/year vs. 0.2%/year, P < 0.0001) studies. Multivariate Cox
      proportional hazards analysis identified number of new ischemic wall-motion
      abnormalities as the strongest predictor of cardiac events (P < 0.05) in both
      groups. CONCLUSIONS: Despite normal stress echocardiography, the inability to
      achieve 85% MPHR conferred a higher, intermediate cardiac event rate of
      2.9%/year. The ability to achieve 9 minutes (>= 10 metabolic equivalents, METS)
      conferred an overall low cardiac event rate of 0.4%/year. However, the absence or
      presence of ischemia by stress echocardiography was able to further risk stratify
      patients with either submaximal or high exercise capacity studies.

PMID- 24304165
TI  - Connexin36 in gap junctions forming electrical synapses between motoneurons in
      sexually dimorphic motor nuclei in spinal cord of rat and mouse.
AB  - Pools of motoneurons in the lumbar spinal cord innervate the sexually dimorphic
      perineal musculature, and are themselves sexually dimorphic, showing differences
      in number and size between male and female rodents. In two of these pools, the
      dorsomedial nucleus (DMN) and the dorsolateral nucleus (DLN), dimorphic
      motoneurons are intermixed with non-dimorphic neurons innervating anal and
      external urethral sphincter muscles. As motoneurons in these nuclei are
      reportedly linked by gap junctions, we examined immunofluorescence labeling for
      the gap junction-forming protein connexin36 (Cx36) in male and female mice and
      rats. Fluorescent Cx36-labeled puncta occurred in distinctly greater amounts in
      the DMN and DLN of male rodents than in other spinal cord regions. These puncta
      were localized to motoneuron somata, proximal dendrites, and neuronal
      appositions, and were distributed either as isolated or large patches of puncta.
      In both rats and mice, Cx36-labeled puncta were associated with nearly all (>
      94%) DMN and DLN motoneurons. The density of Cx36-labeled puncta increased
      dramatically from postnatal days 9 to 15, unlike the developmental decreases in
      these puncta observed in other central nervous system regions. In females, Cx36
      labeling of puncta in the DLN was similar to that in males, but was sparse in the
      DMN. In enhanced green fluorescent protein (EGFP)-Cx36 transgenic mice,
      motoneurons in the DMN and DLN were intensely labeled for the EGFP reporter in
      males, but less so in females. The results indicate the presence of Cx36
      containing gap junctions in the sexually dimorphic DMN and DLN of both male and
      female rodents, suggesting coupling of not only sexually dimorphic but also non
      dimorphic motoneurons in these nuclei.

PMID- 24304168
TI  - Risk factors for the progression of periodontal attachment loss: a 5-year
      population-based study in South Brazil.
AB  - AIM: To assess sociodemographic and behavioural risk factors for periodontal
      attachment loss (PAL) progression after 5 years in an urban sample from south
      Brazil. METHODS: At baseline, 1586 subjects, 14 years and older, were derived
      using a multistage probabilistic sample strategy. At follow-up, 653 of 755
      subjects had >=6 teeth and were included in this analysis. A modified multiple
      Poisson regression was used to calculate adjusted relative risks (RR) and 95%
      confidence intervals (CI). RESULTS: Overall, 247 (37.8%) subjects exhibited PAL
      progression >=3 mm in >=4 teeth. Subjects older than 30 years had approximately
      two times higher risk of having PAL progression than younger subjects. Subjects
      with low education had 53% higher risk (RR = 1.53; 95% CI:1.06-2.22) of PAL
      progression compared to those with high education. A significant interaction
      between gender and smoking was observed. Among never-smokers, males were 33% more
      likely (RR = 1.33; 95% CI:1.06-1.66) to experience PAL progression than females.
      Among smokers, there was 8% increased risk of PAL progression (RR = 1.08; 95%
      CI:1.01-1.14) for males and 21% (RR = 1.21; 95% CI:1.11-1.33) for females per 10
      packyears. Skin colour, socioeconomy, dental care and diabetes were not
      significantly associated with PAL progression after statistical adjustment.
      CONCLUSION: Sociodemographic factors and smoking are independent risk factors for
      PAL progression in this Brazilian population.

PMID- 24304169
TI  - In vitro and in vivo metabolism of a novel chymase inhibitor, SUN13834, and the
      predictability of human metabolism using mice with humanized liver.
AB  - 1. A novel oral chymase inhibitor, SUN13834, is under clinical development for
      the treatment of atopic dermatitis (AD). In this study, in vitro and in vivo
      metabolic profiles of SUN13834 were compared between severe combined
      immunodeficiency (SCID) mice, chimeric mice with humanized liver and humans. 2.
      In in vitro experiments using liver microsomes, predominant metabolites of
      SUN13834 were glucuronide (MG-1) in SCID mice and hydroxylated metabolite (M-3)
      in chimeric mice and humans. 3. After a single oral dose of [(14)C]SUN13834 to
      SCID and chimeric mice, glucuronidation was the major metabolic pathway in SCID
      mice, while the parent compound, ring opening form (M-5), O-demethylated form of
      M-5 (M-6) and glucuronidation of M-6 (M-6G) were detected at higher levels in
      chimeric mice compared to SCID mice. 4. When AD patients were orally treated
      using SUN13834 for 28 days, the parent compound had the highest concentration in
      plasma, and M-6, M-6G, M-5 and MG-1 were identified as major metabolites. 5. This
      is the first report of SUN13834 metabolic information in human. In addition,
      based on similarities in metabolic profiles between chimeric mice and humans, it
      was concluded that chimeric mice are useful for predicting SUN13834 metabolism in
      humans during early stages of drug development.

PMID- 24304170
TI  - Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl
      peptidase 4 inhibitor, in humans.
AB  - 1. Gemigliptin (formerly known as LC15-0444) is a newly developed dipeptidyl
      peptidase 4 inhibitor for the treatment of type 2 diabetes. Following oral
      administration of 50 mg (5.4 MBq) [(14)C]gemigliptin to healthy male subjects,
      absorption, metabolism and excretion were investigated. 2. A total of 90.5% of
      administered dose was recovered over 192 hr postdose, with 63.4% from urine and
      27.1% from feces. Based on urinary recovery of radioactivity, a minimum 63.4%
      absorption from gastrointestinal tract could be confirmed. 3. Twenty-three
      metabolites were identified in plasma, urine and feces. In plasma, gemigliptin
      was the most abundant component accounting for 67.2% ~ 100% of plasma
      radioactivity. LC15-0636, a hydroxylated metabolite of gemigliptin, was the only
      human metabolite with systemic exposure more than 10% of total drug-related
      exposure. Unchanged gemigliptin accounted for 44.8% ~ 67.2% of urinary
      radioactivity and 27.7% ~ 51.8% of fecal radioactivity. The elimination of
      gemigliptin was balanced between metabolism and excretion through urine and
      feces. CYP3A4 was identified as the dominant CYP isozyme converting gemigliptin
      to LC15-0636 in recombinant CYP/FMO enzymes.

PMID- 24304171
TI  - Addiction, drinking behavior, and driving under the influence.
AB  - Using a survey of drinkers (N = 1,634), we evaluated alternative explanations of
      heavy and binge drinking, driving under the influence (DUI), DUI arrests,
      speeding citations, and chargeable accidents. Explanations included socializing,
      short-term decision-making, unrealistic optimism, risk preferring behavior, and
      addiction. Most consistent relationships were between substance use and alcohol
      addiction and dependent variables for (1) binge drinking and (2) DUI episodes.
      Respondent characteristics (age, marital and employment status, race, etc.) had
      important roles for DUI arrests. Drinker-drivers and those arrested for DUI are
      partially overlapping groups with implications for treatment and policies
      detecting and incapacitating persons from drinking and driving. 

PMID- 24304172
TI  - A study of multiple behavioral addictions in a substance abuse sample.
AB  - Behavioral addictions (BAs) are underrecognized, even in addiction programs. We
      assessed BAs in a substance abuse sample (n = 51; data collection 2011-2012). A
      self-report Behavioral Addictions Screen, assessing eight BAs, was administered
      using an automated telephone system. Most endorsed at least one BA, with the most
      common shopping/spending; eating; work; computer/internet; and sex/pornography.
      Lowest were gambling, self-harm, and exercise. Some BAs were correlated with
      others. Gender, ethnicity, age, and positive depression and posttraumatic stress
      disorder screens were associated with specific BAs. Future research could address
      interpretation of "addiction," comparison to diagnostic interviews, relationship
      to substance use disorders, and larger samples. 

PMID- 24304173
TI  - Complete LVOT obstruction following aortic valve replacement after HeartMate II
      implantation.

PMID- 24304174
TI  - Acute fatty liver of pregnancy: a retrospective study of 32 cases in South China.
AB  - OBJECTIVE: To describe 32 cases of acute fatty liver of pregnancy (AFLP) and
      identify the potential clinical predictors of maternal and fetal outcomes in
      South China. METHODS: Thirty-two cases of AFLP previously treated in the First
      Affiliated Hospital of Nanchang University in the past 10 years were enrolled in
      the current study. RESULTS: Sex of fetus and delivery method was the potential
      clinical predictor of fetal outcome. The main manifestations of AFLP were
      jaundice (n = 32), nausea and vomiting (n = 28), malaise (n = 25), and ascites (n
      = 25), and its complications included acute renal failure (n = 26), hepatic
      encephalopathy (n = 17), infection (n = 10), and postpartum hemorrhage (n = 7).
      Evidence of fatty changes of liver was demonstrated by B ultrasound and computed
      tomography (CT). Eighteen patients were recovered due to rapid diagnosis, early
      termination of pregnancy and supportive treatments. CONCLUSIONS: Male sex and
      vaginal delivery was the risk factor of fetal outcome. Detailed history taking
      and proper management of potential predictors are important in making the
      decision of prompt delivery and choosing the appropriate delivery method. Further
      studies are needed to expand our knowledge on this disease.

PMID- 24304175
TI  - Genetically engineered myoblast sheet for therapeutic angiogenesis.
AB  - Peripheral arterial disease is a common manifestation of systemic
      atherosclerosis, which results in more serious consequences of ischemic events in
      peripheral tissues such as the lower extremities. Cell therapy has been tested as
      a treatment for peripheral ischemia that functions by inducing angiogenesis in
      the ischemic region. However, the poor survival and engraftment of transplanted
      cells limit the efficacy of cell therapy. In order to overcome such challenges,
      we applied genetically engineered cell sheets using a cell-interactive and
      thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast
      sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a
      highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were
      then transfected with vascular endothelial growth factor (VEGF) plasmids using
      poly(beta-amino ester) nanoparticles to increase the angiogenic potential of the
      sheets. The transfection increased the VEGF expression and secretion from the
      C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets
      was confirmed using an in vitro capillary formation assay. More importantly, the
      transplantation of the VEGF-transfected C2C12 sheets promoted the formation of
      capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis
      and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss.
      In conclusion, the combination of cell sheet engineering and genetic modification
      can provide more effective treatment for therapeutic angiogenesis. 

PMID- 24304176
TI  - Mapping biopsy with punch biopsies to determine surgical margin in extramammary
      Paget's disease.
AB  - It is difficult to determine the appropriate resection margin of extramammary
      Paget's disease (EMPD). A high recurrence rate is reported in spite of using Mohs
      micrographic surgery (MMS), which is performed commonly. Preoperative mapping
      biopsy is easier to perform than MMS. In Japan, the following method is
      recommended instead of MMS: well-defined border and margins histologically
      confirmed by mapping biopsy should be resected with 1-cm margin and ill-defined
      border with 3-cm margin. This study aimed to evaluate the accuracy of the
      Japanese guideline and to assess our mapping biopsy method compared with MMS.
      Preoperative mapping biopsy specimens were obtained beyond the clinical border
      for at least four directions in each patient. To confirm the presence of residual
      Paget's cells postoperatively, narrow specimens were obtained along the surgical
      margin. Retrospective evaluation of 17 EMPD patients was conducted concerning
      histological spread of Paget's cells and recurrence ratio. There were 86
      directions showing a well-defined border, and in 9.3% (8/86), Paget's cells were
      still observed at 1-cm resection line. On the other hand, there were 21
      directions showing an ill-defined border, and unnecessary radical resection was
      performed in 90% (19/21) of directions with 3-cm resection line. Although
      postoperative histological examination showed residual Paget's cells in 47%
      (8/17) of patients and additional resections were not performed, recurrence rate
      was only 5.9% (1/17). The resection line of EMPD should be based not on clinical
      features, but on mapping biopsy. Mapping biopsy is equivalent to MMS concerning
      recurrence rate and, though conventional, is useful method to treat EMPD. 

PMID- 24304177
TI  - Scandium pentafluorobenzoate-catalyzed unexpected cascade reaction of 2
      aminobenzaldehydes with primary amines: a process for the preparation of ring
      fused aminals.
AB  - An unexpected cascade reaction of 2-aminobenzaldehydes with arylamines catalyzed
      by scandium pentafluorobenzoate [Sc(Pfb)3] was reported as a facile strategy for
      the efficient synthesis of a novel class of polycyclic ring-fused aminals N
      substituted-6,7,11b,13-tetrahydro-6,12-[1,2]benzenoquinazolino[3,4-a]quinazolin
      13-amines 1. Under similar conditions, a series of the analogues of Troger's
      base, 13-substituted-5,6,11,12-tetrahydro-6,12-epiminodibenzo[b,f][1,5]diazocines
      2 were obtained when the arylamines were replaced by methanamines. A possible
      mechanism for the formation of 1 and 2 was proposed. 

PMID- 24304178
TI  - CdS quantum dots doped tuning of deswelling kinetics of thermoresponsive
      hydrogels based on poly(2-(2-methoxyethoxy)ethyl methacrylate).
AB  - Thermoresponsive poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA) based
      hybrid nanocomposite hydrogels (NCH) were synthesized by dispersing preformed
      cadmium sulfide (CdS) quantum dots (QDs) in the reaction mixture followed by
      polymerization via reversible addition-fragmentation chain transfer (RAFT)
      technique. High doping capacity and negligible QDs leakage were observed for
      hydrophilic QDs doped hydrogels (hpl-NCH) due to H-bonding interactions between
      QDs and pendant groups of hydrogel network. The hpl-NCH networks showed improved
      structural/orientational order and swelling ratios with increasing doping
      concentration compared to the organic hydrogel (OH). Opposite trends were
      observed for bulk-CdS (NCH-bulk) and 1-dodecanethiol capped CdS (NCH-DDT) doped
      hydrogels. Swelling induced linear retardance and quenching of photoluminescence
      (PL) intensity for hydrogels were exploited to study the deswelling kinetics
      respectively by Mueller matrix polarimetry and solid state fluorimetry, which
      were further corroborated with gravimetric analysis. For all the NCH, deswelling
      process significantly decreased with increasing temperature, which followed the
      order: 30 > 45 > 60  degrees C. Slower deswelling was observed for NCH-bulk and
      hpl-NCH compared to the OH, and also with increase in doping concentration due to
      the formation of skin layer. However, NCH-DDT exhibited accelerated deswelling
      process and the order was reversed with respect to doping concentration due to
      DDT mediated enhanced hydrophobic aggregation and water leakage channels created
      by long hydrophobic free-mobile nature of QDs surface tethered DDT molecules. The
      presented methodology provides tunable deswelling of PMEO2MA based hydrogels by
      doping with hydrophilically/hydrophobically modified CdS QDs. 

PMID- 24304179
TI  - The additional value of blood cultures in patients with complicated urinary tract
      infections.
AB  - We evaluated 800 hospitalized patients with a complicated urinary tract
      infection, from whom both a blood and a urine culture were obtained on the first
      day of antibiotic treatment. Urine cultures were positive in 70% of patients, and
      blood cultures were positive in 29%. In 7% of patients, uropathogens caused
      bacteraemia with a pathogen that was not isolated from urine. Receiving
      antibiotic therapy at the moment of hospitalization was the only factor
      independently associated with discordant culture results (OR, 2.06; 95% CI, 1.18
      3.61). For those receiving antibiotics at the moment of hospitalization, blood
      cultures have additional diagnostic value over urine cultures. 

PMID- 24304180
TI  - Physician assistants in American medicine: the half-century mark.
AB  - BACKGROUND: The concept of the physician assistant (PA) was developed by US
      physicians in the 1960s as a workforce strategy to improve the delivery of
      medical services. Then as now there is an anticipated shortage of physicians,
      particularly in primary care. Use of PAs is viewed as 1 possible strategy to
      mitigate this growing gap in provider services. OBJECTIVES: To describe the PA in
      US medicine for policy background and analysis. DESCRIPTION: In January 2013,
      approximately 89,500 PAs were licensed: 65% were women. Four-fifths were under
      the age of 55 years. PAs are trained in 2.5 years at one-fourth the cost of a
      physician and begin producing patient care 4 years before a physician is
      independently functional. One-third of PAs work with primary care physicians; 65%
      work in non-primary care practices. Popular specialties are family medicine,
      emergency medicine, surgery, and orthopedics. PAs are revenue producers for
      employers and expand access and clinical productivity in most practice settings.
      Roles for PAs have expanded into hospital settings and graduate medical education
      programs. About 7300 PAs graduate annually, and this number is expected to grow
      to 9000 by the end of the decade. Predictive modeling suggests that demand for
      medical services will grow faster than the combined supply of physicians, PAs,
      and nurse practitioners, particularly in primary care. PA quality of care appears
      indistinguishable from that of physician-delivered services. CONCLUSIONS: Optimal
      organizational efficiency and cost savings in health services delivery will
      depend on how well the PA can be utilized.

PMID- 24304181
TI  - How do providers prioritize prevention? A qualitative study.
AB  - BACKGROUND: Preventive care is an essential element of comprehensive primary care
      medicine, yet many providers do not address the full range of recommended
      preventive care services. There is little understanding of how, during time
      constrained clinical encounters, providers prioritize preventive care services.
      OBJECTIVES: To identify and compare how Department of Veterans Affairs (VA)
      primary care providers (PCPs) prioritized general preventive care services,
      including HIV testing. STUDY DESIGN: A semistructured, qualitative interview
      design. METHODS: We conducted semistructured phone interviews with 31 PCPs across
      2 urban VA facilities. Interviews entailed questions about the most common
      preventive care services in primary care, how decisions are made to address some
      preventive care services but not others, and the role of clinical reminders (CRs)
      in prioritizing care. Interviews were audio-recorded and transcribed verbatim. We
      conducted an iterative thematic analysis of interview transcripts, utilizing
      NVivo 8, a qualitative data management and coding software. RESULTS: Most PCPs
      indicated they did not utilize CRs as a primary means of prioritizing general
      preventive care. Instead, PCPs prioritized general preventive care by attending
      to patients' individual needs and/or keeping in mind influential clinical
      training experiences. Prioritizing HIV testing included 1 or a combination of the
      following strategies: being attuned to HIV risk factors prior to the appearance
      of the CR, being prompted by the CR, and having a positive attitude toward CR
      design. CONCLUSIONS: Prioritizing preventive care can be accomplished using
      various strategies, including CRs. Healthcare systems might benefit from
      encouraging PCPs to use a range of strategies.

PMID- 24304182
TI  - Outcomes among chronically ill adults in a medical home prototype.
AB  - OBJECTIVES: To compare quality, utilization, and cost outcomes for patients with
      selected chronic illnesses at a patient-centered medical home (PCMH) prototype
      site with outcomes for patients with the same chronic illnesses at 19
      nonintervention control sites. STUDY DESIGN: Nonequivalent pretest-posttest
      control group design. METHODS: PCMH redesign results were investigated for
      patients with preexisting diabetes, hypertension, and/or coronary heart disease.
      Data from automated databases were collected for eligible enrollees in an
      integrated healthcare delivery system. Multivariable regression models tested for
      adjusted differences between PCMH patients and controls during the baseline and
      follow-up periods. Dependent measures under study included clinical processes
      and, outcomes, monthly healthcare utilization, and costs. RESULTS: Compared with
      controls over 2 years, patients at the PCMH prototype clinic had slightly better
      clinical outcome control in coronary heart disease (2.20 mg/dL lower mean low
      density lipoprotein cholesterol; P <.001). PCMH patients changed their patterns
      of primary care utilization, as reflected by 86% more secure electronic message
      contacts (P <.001), 10% more telephone contacts (P = .003), and 6% fewer in
      person primary care visits (P <.001). PCMH patients had 21% fewer ambulatory care
      sensitive hospitalizations (P <.001) and 7% fewer total inpatient admissions (P =
      .002) than controls. During the 2-year redesign, we observed 17% lower inpatient
      costs (P <.001) and 7% lower total healthcare costs (P <.001) among patients at
      the PCMH prototype clinic. CONCLUSIONS: A clinic-level population-based PCMH
      redesign can decrease downstream utilization and reduce total healthcare costs in
      a subpopulation of patients with common chronic illnesses.

PMID- 24304183
TI  - Performance measurement for people with multiple chronic conditions: conceptual
      model.
AB  - BACKGROUND: Improving quality of care for people with multiple chronic conditions
      (MCCs) requires performance measures reflecting the heterogeneity and scope of
      their care. Since most existing measures are disease specific, performance
      measures must be refined and new measures must be developed to address the
      complexity of care for those with MCCs. OBJECTIVES: To describe development of
      the Performance Measurement for People with Multiple Chronic Conditions (PM-MCC)
      conceptual model. STUDY DESIGN: Framework development and a national stakeholder
      panel. METHODS: We used reviews of existing conceptual frameworks of performance
      measurement, review of the literature on MCCs, input from experts in the
      multistakeholder Steering Committee, and public comment. RESULTS: The resulting
      model centers on the patient and family goals and preferences for care in the
      context of multiple care sites and providers, the type of care they are
      receiving, and the national priority domains for healthcare quality measurement.
      CONCLUSIONS: This model organizes measures into a comprehensive framework and
      identifies areas where measures are lacking. In this context, performance
      measures can be prioritized and implemented at different levels, in the context
      of patients' overall healthcare needs.

PMID- 24304184
TI  - Pedestrian and motorists' actions at pedestrian hybrid beacon sites: findings
      from a pilot study.
AB  - This paper focuses on an analysis of pedestrian and motorists' actions at sites
      with pedestrian hybrid beacons and assesses their effectiveness in improving the
      safety of pedestrians. Descriptive and statistical analyses (one-tail two-sample
      T-test and two-proportion Z-test) were conducted using field data collected
      during morning and evening peak hours at three study sites in the city of
      Charlotte, NC, before and after the installation of pedestrian hybrid beacons.
      Further, an analysis was conducted to assess the change in pedestrian and
      motorists' actions over time (before the installation; 1 month, 3 months, 6
      months, and 12 months after the installation). Results showed an increase in
      average traffic speed at one of the pedestrian hybrid beacon sites while no
      specific trends were observed at the other two pedestrian hybrid beacon sites. A
      decrease in the number of motorists not yielding to pedestrians, pedestrians
      trapped in the middle of the street, and pedestrian-vehicle conflicts were
      observed at all the three pedestrian hybrid beacon sites. The installation of
      pedestrian hybrid beacons did not have a negative effect on pedestrian actions at
      two out of the three sites. Improvements seem to be relatively more consistent 3
      months after the installation of the pedestrian hybrid beacon. 

PMID- 24304185
TI  - Analysis of patients' narratives posted on social media websites on benfluorex's
      (Mediator(r) ) withdrawal in France.
AB  - WHAT IS KNOWN AND OBJECTIVE: Websites and discussion lists on health issues are
      among the most popular resources on the Web. Use experience reported on social
      media websites may provide useful information on drugs and their adverse
      reactions (ADRs). Clear communication on the benefit/harm balance of drugs is
      important to inform proper use of drugs. Some data have shown that communication
      (advisories or warnings) is difficult. This study aimed to explore the Internet
      as a source of data on patients' perception of risk associated with benfluorex
      and the impact of wider media coverage. METHODS: Three French websites were
      selected: Doctissimo, Atoute.org considered the best-known and visited website in
      France for health questions and Vivelesrondes (Long live the Tubbies) for
      overweight people. Three periods were chosen: (1) before November 2009 (i.e.
      before benfluorex withdrawal), (2) between November 2009 and November 2010 (when
      the risk of valvulopathy with benfluorex appeared in social media) and (3) after
      November 2010. RESULTS AND DISCUSSION: Two hundred twenty initial postings were
      analysed. These lead to 660 secondary postings which were analysed separately. In
      period 1, 114 initial postings were analysed, mostly concerning efficacy of the
      drug (72%). In period 2, 42 initial postings were analysed involving mainly ADRs
      or warnings (73%). In period 3, 64 initial postings were analysed; most frequent
      expressing anger directed at the healthcare system (58%) and anxiety about
      cardiovascular ADRs (30%). Online consumer postings showed that there were
      drastic changes in consumers' perceptions following media coverage. WHAT IS NEW
      AND CONCLUSION: This study suggests that analysis of website data can inform on
      drug ADRs. Social media are important for communicating information on drug ADRs
      and for assessing consumer behaviour and their risk perception.

PMID- 24304187
TI  - A novel mutation of the leptin gene in an Indian patient.

PMID- 24304188
TI  - Galactofuranose-coated gold nanoparticles elicit a pro-inflammatory response in
      human monocyte-derived dendritic cells and are recognized by DC-SIGN.
AB  - Galactofuranose (Galf) is the five-membered ring form of galactose exclusively
      found in nonmammalian species, among which several are pathogens. To determine
      the putative role of this carbohydrate in host-pathogen interactions, we
      synthesized multivalent gold nanoparticles carrying Galf (Galf-GNPs) and show
      that they are recognized by the EB-A2 antibody, which is widely used to detect
      Galf-containing galactomannan in the serum of Aspergillosis patients. We
      demonstrated that human monocyte-derived dendritic cells bound Galf-GNPs via
      interaction with the lectin DC-SIGN. Moreover, interaction of dendritic cells
      with Galf-GNPs resulted in increased expression of several maturation markers on
      these cells and induced secretion of the pro-inflammatory cytokines IL-6 and TNF
      alpha. These data indicate that Galf is able to modulate the innate immune
      response via dendritic cells. In conclusion, Galf-GNPs are a versatile tool that
      can be applied in multiple functional studies to gain a better understanding of
      the role of Galf in host-pathogen interaction. 

PMID- 24304189
TI  - Editorial comment from Dr Armitage to tubeless simultaneous bilateral
      percutaneous nephrolithotomy: safety, feasibility and efficacy in an Indian
      setting.

PMID- 24304186
TI  - Widespread microRNA dysregulation in multiple system atrophy - disease-related
      alteration in miR-96.
AB  - MicroRNA (miRNA) are short sequences of RNA that function as post-transcriptional
      regulators by binding to target mRNA transcripts resulting in translational
      repression. A number of recent studies have identified miRNA as being involved in
      neurodegenerative disorders including Alzheimer's disease, Parkinson's disease
      and Huntington's disease. However, the role of miRNA in multiple system atrophy
      (MSA), a progressive neurodegenerative disorder characterized by oligodendroglial
      accumulation of alpha-synuclein remains unexamined. In this context, this study
      examined miRNA profiles in MSA cases compared with controls and in transgenic
      (tg) models of MSA compared with non-tg mice. The results demonstrate a
      widespread dysregulation of miRNA in MSA cases, which is recapitulated in the
      murine models. The study employed a cross-disease, cross-species approach to
      identify miRNA that were either specifically dysregulated in MSA or were commonly
      dysregulated in neurodegenerative conditions such as Alzheimer's disease,
      dementia with Lewy bodies, progressive supranuclear palsy and corticobasal
      degeneration or the tg mouse model equivalents of these disorders. Using this
      approach we identified a number of miRNA that were commonly dysregulated between
      disorders and those that were disease-specific. Moreover, we identified miR-96 as
      being up-regulated in MSA. Consistent with the up-regulation of miR-96, mRNA and
      protein levels of members of the solute carrier protein family SLC1A1 and SLC6A6,
      miR-96 target genes, were down-regulated in MSA cases and a tg model of MSA.
      These results suggest that miR-96 dysregulation may play a role in MSA and its
      target genes may be involved in the pathogenesis of MSA. 

PMID- 24304190
TI  - Highly stable hexacoordinated nonoxidovanadium(IV) complexes of sterically
      constrained ligands: syntheses, structure, and study of antiproliferative and
      insulin mimetic activity.
AB  - Three highly stable, hexacoordinated nonoxidovanadium(IV), V(IV)(L)2, complexes
      (1-3) have been isolated and structurally characterized with tridentate
      aroylhydrazonates containing ONO donor atoms. All the complexes are stable in the
      open air in the solid state as well as in solution, a phenomenon rarely observed
      in nonoxidovanadium(IV) complexes. The complexes have good solubility in organic
      solvents, permitting electrochemical and various spectroscopic investigations.
      The existence of nonoxidovanadium(IV) complexes was confirmed by elemental
      analysis, ESI mass spectroscopy, cyclic voltammetry, EPR, and magnetic
      susceptibility measurements. X-ray crystallography showed the N3O3 donor set to
      define a trigonal prismatic geometry in each case. All the complexes show in
      vitro insulin mimetic activity against insulin responsive L6 myoblast cells, with
      complex 3 being the most potent, which is comparable to insulin at the complex
      concentration of 4 MUM, while the others have moderate insulin mimetic activity.
      In addition, the in vitro antiproliferative activity of complexes 1-3 against the
      HeLa cell line was assayed. The cytotoxicity of the complexes is affected by the
      various functional groups attached to the bezoylhydrazone derivative and 2 showed
      considerable antiproliferative activity compared to the most commonly used
      chemotherapeutic drugs. 

PMID- 24304191
TI  - miRNA expression profiles determined in maternal sera of patients with HELLP
      syndrome.
AB  - OBJECTIVE: Syndrome of hemolysis, elevated liver enzymes and low platelets
      (HELLP) represents a distinct subgroup of severe preeclampsia. The aim of our
      study was to identify differentially expressed miRNAs in sera of patients with
      HELLP syndrome in comparison to unaffected controls. STUDY DESIGN: Blood samples
      were obtained from patients with manifest HELLP syndrome and matched unaffected
      controls. The expression of 754 mature miRNAs was assessed using the TaqMan Array
      format (n = 12). Results of seven differentially expressed miRNAs were further
      validated by single quantitative real-time polymerase chain reaction (qPCR)
      assays. RESULTS: Serum miRNA analysis allowed detection of maternal and fetal
      miRNAs. Distinct miRNA expressions were confirmed for miR-122, miR-758 and miR
      133a represented by a median up-regulation >= two-fold in the HELLP group. The
      liver specific miR-122 was 11.5-fold increased with an area under curve (AUC) of
      0.82 in the receiver operating characteristic (ROC) analysis. Cluster analyses of
      our data uncovered subgroups of HELLP patients were associated with clinical
      subtypes and differences in organ manifestation. CONCLUSION: In our proof of
      principle study, we demonstrated that patients with HELLP syndrome showed
      alterations of serum miRNA expression patterns. Data analysis goes along with the
      hypothesis that HELLP syndrome is regarded to be a heterogeneous disease.

PMID- 24304193
TI  - Formation and structural characteristics of thermosensitive multiblock copolymer
      vesicles.
AB  - The spontaneous vesicle formation of ABABA-type amphiphilic multiblock copolymers
      bearing thermosensitive hydrophilic A-block in a selective solvent is studied
      using dissipative particle dynamics (DPD) approach. The formation process of
      vesicle through nucleation and growth pathway is observed by varying the
      temperature. The simulation results show that spherical micelle takes shape at
      high temperature. As temperature decreases, vesicles with small aqueous cavity
      appear and the cavity expands as well as the membrane thickness decreases with
      the temperature further decreasing. This finding is in agreement with the
      experimental observation. Furthermore, by continuously varying the temperature
      and the length of the hydrophobic block, a phase diagram is constructed, which
      can indicate the thermodynamically stable region for vesicles. The morphological
      phase diagram shows that vesicles can form in a larger parameter scope. The
      relationship between the hydrophilic and hydrophobic block length versus the
      aqueous cavity size and vesicle size are revealed. Simulation results demonstrate
      that the copolymers with shorter hydrophobic blocks length or the higher
      hydrophilicity are more likely to form vesicles with larger aqueous cavity size
      and vesicle size as well as thinner wall thickness. However, the increase in A
      block length results to form vesicles with smaller aqueous cavity size and larger
      vesicle size. 

PMID- 24304192
TI  - Advanced tissue engineering scaffold design for regeneration of the complex
      hierarchical periodontal structure.
AB  - AIM: This study investigated the ability of an osteoconductive biphasic scaffold
      to simultaneously regenerate alveolar bone, periodontal ligament and cementum.
      MATERIALS AND METHODS: A biphasic scaffold was built by attaching a fused
      deposition modelled bone compartment to a melt electrospun periodontal
      compartment. The bone compartment was coated with a calcium phosphate (CaP) layer
      for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro
      for 6 weeks. The resulting constructs were then complemented with the placement
      of PDL cell sheets on the periodontal compartment, attached to a dentin block and
      subcutaneously implanted into athymic rats for 8 weeks. Scanning electron
      microscopy, X-ray diffraction, alkaline phosphatase and DNA content
      quantification, confocal laser microscopy, micro computerized tomography and
      histological analysis were employed to evaluate the scaffold's performance.
      RESULTS: The in vitro study showed that alkaline phosphatase activity was
      significantly increased in the CaP-coated samples and they also displayed
      enhanced mineralization. In the in vivo study, significantly more bone formation
      was observed in the coated scaffolds. Histological analysis revealed that the
      large pore size of the periodontal compartment permitted vascularization of the
      cell sheets, and periodontal attachment was achieved at the dentin interface.
      CONCLUSIONS: This work demonstrates that the combination of cell sheet technology
      together with an osteoconductive biphasic scaffold could be utilized to address
      the limitations of current periodontal regeneration techniques.

PMID- 24304194
TI  - Aneurysmally dilated giant coronary sinus mimicking accessory cardiac chamber.

PMID- 24304195
TI  - 3D echocardiography in cardiac surgery.
AB  - Herein, we present a patient who underwent successful repair of failed mitral
      valve repair in whom intraoperative 3D transesophageal echocardiography provided
      accurate assessment of the mechanism of mitral regurgitation. In addition, we
      review the potential advantages and limitations of 3D echocardiography and its
      role in cardiac surgery.

PMID- 24304196
TI  - Effect of cryotherapy on the lumbar spine in elderly men with back pain.
AB  - Whole-body cryotherapy (WBC) is a procedure which is more and more often
      successfully applied in medicine. Used in physiotherapy programs improves the
      efficiency of physiotherapeutic exercises applied in different aliments. The aim
      of the research was to determine the influence of WBC treatment on the
      improvement of spine activity in elderly men. The evaluation was based on
      subjects suffering from chronic lower back pain. The research was conducted on 96
      male in the age of 65-75 years suffering from chronic pain in the lumbar spine,
      lasting >3 months. All the subjects performed physical exercises at a gym. Half
      of the examined patients performed only physical exercises while the second half
      of the group participated in WBC before performing the same exercises. The
      research evaluated the mobility of lumbar spine at all movement planes and
      examined the values of active potentials of erector spinae in the lumbar part of
      the spine. The group of men who participated in WBC showed significantly lower
      values of active potentials of erector spinae muscles in the lumbar part of the
      spine and a significant increase in the range of the lumbar spine mobility, in
      comparison to the group which did not use WBC.

PMID- 24304197
TI  - Emerging trabecular outflow drugs.

PMID- 24304198
TI  - Effect of vitamin D3 on lifespan in Caenorhabditis elegans.
AB  - Vitamin D is an essential micronutrient, necessary for human health. To determine
      if Caenorhabditis elegans (C. elegans) could function as an effective model to
      study the mechanisms of action of vitamin D, we asked if vitamin D3 affects C.
      elegans lifespan. Multiple factors positively impact lifespan in this system
      including dietary restriction and vitamin E. In addition, the C. elegans DAF-12
      nuclear hormone receptor is homologous to the vitamin D receptor in humans and is
      therefore a candidate for a functional vitamin D receptor. It was hypothesized
      that vitamin D3 supplementation would increase the lifespan of C. elegans in a
      DAF-12-dependent manner. Dose-response curves were completed, and results
      indicate that exposure to 1,000 ug/ml vitamin D3 significantly increased the
      lifespan of wild-type worms by up to 39% (p<0.001). The daf-12 mutants exposed to
      1,000 ug/ml vitamin D3 lived significantly longer than daf-12 controls exposed to
      0 ug/ml (p<0.001), but among worms exposed to 1,000 ug/ml vitamin D3, wild type
      lived significantly longer than daf-12 (p<0.01). The data suggest that vitamin D3
      can interact with multiple receptors, possibly implicating the NHR family of
      nuclear hormone receptors related to DAF-12. This research is the first to our
      knowledge to utilize C. elegans as a model to study the impact of vitamin D3 on
      longevity and supports the use of this model system to increase our understanding
      of vitamin D function at the cellular level, its role in cellular health, and its
      potential medicinal utility in humans. 

PMID- 24304199
TI  - Creatine supplementation: can it improve quality of life in the elderly without
      associated resistance training?
AB  - INTRODUCTION: Ageing is associated with decreased muscle mass, strength, power
      and function, and reduction in bone density and mineral content, leading to
      reduced independence and increased risk of falls. Creatine supplementation is
      reported to improve muscular strength and performance with training in younger
      athletes, and therefore could benefit older individuals. AIMS: This review
      critically appraises the current literature on whether creatine supplementation
      enhances muscular performance and function, body composition, bone mineral
      density and content in older adults without the addition of resistance training,
      and thus determines whether creatine supplementation can lead to an improved
      lifestyle for the sedentary elderly population. RESULTS: There is conflicting
      evidence regarding the usefulness of creatine supplementation in older subjects.
      Generally, however, creatine supplementation, without associated resistance
      training, seems to enhance muscular strength, power and endurance, increase lean
      body mass (LBM) and improve the functional capacity of the elderly. Furthermore,
      it has been demonstrated that increased muscle mass due to creatine
      supplementation can result in increased local bone density. It appears that the
      effect of creatine supplementation is more beneficial in larger muscles and less
      effective in smaller muscles, however there are exceptions. The mechanism by
      which creatine supplementation works requires further research, however it is
      likely that the effects of creatine are related to creatine kinase activity,
      providing enhanced energy production for greater muscular contraction.
      CONCLUSIONS: These data indicate that creatine supplementation without associated
      training in the elderly could potentially delay atrophy of muscle mass, improve
      endurance and strength, and increase bone strength, and thus may be a safe
      therapeutic strategy to help decrease loss in functional performance of everyday
      tasks.

PMID- 24304200
TI  - Characterisation of mitochondrial DNA deletions by long-PCR in central nervous
      system regions of young, middle- and old-aged rats.
AB  - The causes of ageing remain poorly understood, although a role for mitochondria
      is widely accepted. These unique organelles that are responsible for a cell's
      energy, rely on their own small genome and translational machinery to produce
      proteins that, together with nuclear genome encoded proteins, form the electron
      transport chain complexes necessary for ATP production. Various forms of
      mitochondrial genome mutation and rearrangements are thought to be involved in
      the ageing process, particularly in post-mitotic cells, such as those of the
      nervous system. In the present study, we have characterised mitochondrial DNA
      (mtDNA) deletion mutations in five central nervous system (CNS) regions of the
      young, middle-aged, and old Fischer 344 (F344) rats. DNA was extracted from the
      cerebral cortex, striatum, midbrain, cerebellum and spinal cord, and long-PCR was
      used to detect mtDNA with deletions in the minor and major arcs. This approach
      has the advantage that all deletions can be detected without a priori knowledge
      of breakpoints. In the minor arc, we found evidence for deletions in the striatum
      of five out of six old animals and in the spinal cords from two of six old
      animals. In contrast, mtDNA deletions in the major arc appeared markedly more
      abundant, both in terms of affected CNS regions and number of deleted mtDNA
      molecules. Furthermore, major arc deletions were apparent earlier with a number
      of CNS regions showing deletions in the middle-aged group. The cerebral cortex,
      striatum and spinal cord were the most affected regions, while the midbrain and
      cerebellum were relatively spared. These findings are remarkably consistent with
      previous human brain data and further underscore the value of the rat model for
      investigation of ageing-related changes in the mitochondrial genome. 

PMID- 24304201
TI  - Children's resistance to parents' smoking in the home and car: a qualitative
      study.
AB  - BACKGROUND AND AIMS: Reducing second-hand smoke exposure in the home is a key
      tobacco control goal, yet few studies have explored children's views and
      experiences of this. This study aimed to explore children's accounts of family
      members' smoking in the home and car and the impact of their socio-economic
      circumstances. DESIGN: Individual and friendship group interviews using topic
      guides and visual stimulus methods. SETTING: Two communities in Edinburgh,
      Scotland, one socio-economically advantaged, one socio-economically
      disadvantaged. PARTICIPANTS: Thirty-eight children aged 10-15 years who had a
      close family member who smoked. MEASUREMENTS: Focus group and interview topic
      guides. FINDINGS: Participants in both communities expressed a strong dislike of
      family members' smoking and concern about the potential impact on the smoker's
      health. Participants described overt and covert acts of resistance, including
      challenging relatives about their smoking, expressing disgust and concern, hiding
      or destroying cigarettes. Some acts were carried out in collusion with a non
      smoking parent and/or sibling. Resistant acts were constrained by expectations of
      negative responses, which appeared to increase with age, wider social norms
      around smoking and whether or not the young person smoked. CONCLUSIONS: Some
      children and young people in the United Kingdom, irrespective of socio-economic
      status, may actively oppose parents' smoking in the home and car, although their
      influence may be limited by their position in the family and social norms.

PMID- 24304202
TI  - A preliminary study on the reliability and validity of using experience sampling
      method in children with autism spectrum disorders.
AB  - OBJECTIVE: This study investigated the feasibility of using experience sampling
      method (ESM) to study everyday experiences in children with autism spectrum
      disorders. METHODS: Six boys, aged 8-12 years, with high-functioning autism or
      Asperger syndrome carried an iPod touch with a pre-installed ESM survey about
      what they were doing, where, with whom and the quality of their experiences and
      associated emotions. They were randomly signalled seven times daily for seven
      consecutive days to respond to the survey. RESULTS: The average signal response
      rates (56.8%) was acceptable and the mean time of survey completion (1 minute 53
      seconds) was within acceptable range. Split-week analysis supported the
      consistency of experiences reporting while correlations among theoretically
      linked quality of experiences and emotions showed the internal logic of
      participants' responses; thus supporting internal reliability and validity,
      respectively. CONCLUSION: The study demonstrated the feasibility and usefulness
      of using ESM in exploring participants' everyday life experiences.

PMID- 24304203
TI  - Raltegravir as antiretroviral therapy in HIV/AIDS.
AB  - INTRODUCTION: HIV, a major cause of morbidity and mortality worldwide has been
      transformed by antiretroviral (ARV) therapy into a manageable condition. Drug
      resistance, tolerability and drug interactions remain major concerns when
      choosing ARV therapy. Raltegravir , the first integrase inhibitor in the
      armamentarium against HIV, has been shown to be efficacious in both treatment
      naive and treatment-experienced patients when used in combination as part of
      nucleoside-reverse transcriptase inhibitor-containing regimens. Its key
      advantages include safety, tolerability and fewer drug interactions but it has
      some important limitations such as a lower barrier to resistance and a twice
      daily dosing schedule. Its role in nucleoside-sparing regimens is under
      investigation. AREAS COVERED: PubMed was searched for publications in English
      from 2004 to September 2013 using the terms 'raltegravir', 'integrase inhibitor'
      and 'MK-0518'. Relevant publications were reviewed and reference lists were
      examined for further publications. Conference abstracts from the Conference on
      Retroviruses and Opportunistic Infections, Interscience Conference on
      Antimicrobial Agents and Chemotherapy, and International AIDS Society Conference
      on HIV Pathogenesis, Treatment, and Prevention for 2013 were also reviewed.
      EXPERT OPINION: Raltegravir is an important agent for both naive and experienced
      HIV patients. Its key features include its tolerability, efficacy and lack of
      significant drug interactions.

PMID- 24304204
TI  - Nanofibers support oligodendrocyte precursor cell growth and function as a neuron
      free model for myelination study.
AB  - Nanofiber-based scaffolds may simultaneously provide immediate contact guidance
      for neural regeneration and act as a vehicle for therapeutic cell delivery to
      enhance axonal myelination. Additionally, nanofibers can serve as a neuron-free
      model to study myelination of oligodendrocytes. In this study, we fabricated
      nanofibers using a polycaprolactone and gelatin copolymer. The ratio of the
      gelatin component in the fibers was confirmed by energy dispersive X-ray
      spectroscopy. The addition of gelatin to the polycaprolactone (PCL) for nanofiber
      fabrication decreased the contact angle of the electrospun fibers. We showed that
      both polycaprolactone nanofibers as well as polycaprolactone and gelatin
      copolymer nanofibers can support oligodendrocyte precursor cell (OPC) growth and
      differentiation. OPCs maintained their phenotype and viability on nanofibers and
      were induced to differentiate into oligodendrocytes. The differentiated
      oligodendrocytes extend their processes along the nanofibers and ensheathed the
      nanofibers. Oligodendrocytes formed significantly more myelinated segments on the
      PCL and gelatin copolymer nanofibers than those on PCL nanofibers alone. 

PMID- 24304205
TI  - From ligand fields to molecular orbitals: probing the local valence electronic
      structure of Ni(2+) in aqueous solution with resonant inelastic X-ray scattering.
AB  - Bonding of the Ni(2+)(aq) complex is investigated with an unprecedented
      combination of resonant inelastic X-ray scattering (RIXS) measurements and ab
      initio calculations at the Ni L absorption edge. The spectra directly reflect the
      relative energies of the ligand-field and charge-transfer valence-excited states.
      They give element-specific access with atomic resolution to the ground-state
      electronic structure of the complex and allow quantification of ligand-field
      strength and 3d-3d electron correlation interactions in the Ni(2+)(aq) complex.
      The experimentally determined ligand-field strength is 10Dq = 1.1 eV. This and
      the Racah parameters characterizing 3d-3d Coulomb interactions B = 0.13 eV and C
      = 0.42 eV as readily derived from the measured energies match very well with the
      results from UV-vis spectroscopy. Our results demonstrate how L-edge RIXS can be
      used to complement existing spectroscopic tools for the investigation of bonding
      in 3d transition-metal coordination compounds in solution. The ab initio RASPT2
      calculation is successfully used to simulate the L-edge RIXS spectra. 

PMID- 24304207
TI  - Risk Analysis. From the editors.

PMID- 24304206
TI  - Metal-free coupling of saturated heterocyclic sulfonylhydrazones with boronic
      acids.
AB  - The coupling of aromatic moieties with saturated heterocyclic partners is
      currently an area of significant interest for the pharmaceutical industry.
      Herein, we present a procedure for the metal-free coupling of 4-, 5-, and 6
      membered saturated heterocyclic p-methoxyphenyl (PMP) sulfonylhydrazones with
      aryl and heteroaromatic boronic acids. This procedure enables a simple, two-step
      synthesis of a range of functionalized sp(2)-sp(3) linked bicyclic building
      blocks, including oxetanes, piperidines, and azetidines, from their parent
      ketones. 

PMID- 24304208
TI  - Food allergens in mattress dust in Norwegian homes - a potentially important
      source of allergen exposure.
AB  - BACKGROUND: Sensitization to food allergens and food allergic reactions are
      mostly caused by ingesting the allergen, but can also occur from exposure via the
      respiratory tract or the skin. Little is known about exposure to food allergens
      in the home environment. OBJECTIVE: The objective of this study was firstly to
      describe the frequency of detection of allergens from fish, egg, milk, and peanut
      in mattress dust collected from homes of 13-year-old adolescents and secondly to
      identify home characteristics associated with the presence of food allergen
      contamination in dust. METHODS: Food allergens were measured by dot blot analysis
      in mattress dust from 143 homes in Oslo, Norway. We analysed associations between
      home characteristics (collected by parental questionnaires and study technicians)
      and food allergens by multivariate regression models. RESULTS: Fish allergen was
      detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the
      mattress dust samples; only three samples contained none of these allergens. All
      four food allergens were more frequently detected in mattresses in small
      dwellings (< 100 m(2)) than larger dwellings (>= 130 m(2)); 63-71% of the small
      dwellings (n = 24) had milk, peanut, and fish allergens in the samples compared
      with 33-44% of the larger dwellings (n = 95). Milk, peanut, and egg allergens
      were more frequently detected in homes with bedroom and kitchen on the same floor
      as compared with different floors, with odds ratios of 2.5 (95% confidence
      interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1
      (95% CI: 1.3, 7.5) for egg allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Food
      allergens occurred frequently in beds in Norwegian homes, with dwelling size and
      proximity of kitchen and bedroom as the most important determinants. Due to the
      amount of time children spent in the bedroom, mattress dust may be an important
      source of exposure to food allergens.

PMID- 24304209
TI  - Time- and concentration-dependent effects of exogenous serotonin and inflammatory
      cytokines on mast cell function.
AB  - Mast cells play a significant role in both the innate and adaptive immune
      response; however, the tissue-bound nature of mast cells presents an experimental
      roadblock to performing physiologically relevant mast cell experiments. In this
      work, a heterogeneous cell culture containing primary culture murine peritoneal
      mast cells (MPMCs) was studied to characterize the time-dependence of mast cell
      response to allergen stimulation and the time- and concentration-dependence of
      the ability of the heterogeneous MPMC culture to uptake and degranulate exogenous
      serotonin using high performance liquid chromatography (HPLC) coupled to an
      electrochemical detector. Additionally, because mast cells play a central role in
      asthma, MPMCs were exposed to CXCL10 and CCL5, two important asthma-related
      inflammatory cytokines that have recently been shown to induce mast cell
      degranulation. MPMC response to both allergen exposure and cytokine exposure was
      evaluated for 5-HT secretion and bioactive lipid formation using ultraperformance
      liquid chromatography coupled to an electrospray ionization triple quadrupole
      mass spectrometer (UPLC-MS/MS). In this work, MPMC response was shown to be
      highly regulated and responsive to subtle alterations in a complex environment
      through time- and concentration-dependent degranulation and bioactive lipid
      formation. These results highlight the importance of selecting an appropriate
      mast cell model when studying mast cell involvement in allergic response and
      inflammation. 

PMID- 24304210
TI  - Relationship between nulliparity and preeclampsia may be explained by altered
      circulating soluble fms-like tyrosine kinase 1.
AB  - OBJECTIVE: To test the hypothesis that the risk of preeclampsia in nulliparous
      women may be due to an anti-angiogenic state. METHODS: Maternal serum samples
      obtained in the third trimester from nulliparous (n = 86) and multiparous (n =
      165) singleton uncomplicated pregnancies were analyzed for levels of angiogenic
      factors - soluble fms like tyrosine kinase 1 (sFlt1) and placental growth factor
      (PlGF) by enzyme-linked immunosorbent assay (ELISA). RESULTS: For nulliparous and
      multiparous pregnancies, serum sFlt1 levels were 12 732 +/- 832 and 10 162 +/-
      666 (p = 0.020), serum PlGF levels were 215 +/- 15 and 249 +/- 14 (p = 0.093)
      (all reported as mean SD in pg/ml) and mean ratios of sFlt1/PlGF were 93 +/- 12
      and 62 +/- 5 (p = 0.023), respectively. Adjustment for maternal age and fetal
      birth weight did not alter the results. CONCLUSIONS: Nulliparous pregnancies had
      higher circulating sFlt1 levels and sFlt1/PlGF ratios than multiparous
      pregnancies, suggesting an association with an angiogenic imbalance. Taken
      together with the pathogenic role of anti-angiogenic factors in preeclampsia, our
      data may be one explanation for the epidemiological observation that nulliparity
      is a risk factor for the development of preeclampsia.

PMID- 24304211
TI  - Cost of care for malignant and benign renal masses.
AB  - BACKGROUND: Limitations of current diagnotic techniques may allow some patients
      with presumed renal cell carcinoma (RCC) to undergo nephrectomy without
      definitive confirmation of malignancy. OBJECTIVES: To confirm previous estimates
      of postnephrectomy renal mass diagnosis and to assess the economic impact of
      nephrectomy. METHODS: This retrospective cohort analysis identified commercial
      enrollees who underwent nephrectomy with a diagnosis of RCC between July 1, 2000,
      and March 30, 2008. Study subjects were stratified based on medical claims for
      benign or malignant disease after the nephrectomy date. Cohorts were compared on
      resource utilization before and after nephrectomy, occurrence of postsurgical
      complications, and associated 1-year costs of care. RESULTS: Of 10,404 patients
      undergoing nephrectomy for presumed RCC, 1613 (15.5%) were subsequently
      identified as having benign disease, despite median presurgical diagnostic
      expenditures of $1311 per patient (interquartile range [IQR], $467-$2606). Median
      expenditures for the 12 months postnephrectomy were $26,920 per patient (IQR,
      $16,851-$46,982) for those with malignant disease and $23,951 per patient (IQR,
      $14,873-$38,190) for those with benign disease (P<.0001). For patients with
      benign disease, 17.5% experienced a postsurgical adverse event, resulting in a
      1.5-fold increase in expenditures (median $31,838 per patient for those with
      event vs $22,770 per patient for those without event; P<.0001). CONCLUSIONS: In
      this study, approximately 1 in 6 patients were found to have a benign renal mass
      postnephrectomy. Given the risk of surgical complications and related economic
      consequences, methods for better identifying malignant versus benign disease
      prior to surgery could provide significant benefits to patients and payers.

PMID- 24304212
TI  - Long-term statin use and the risk of Parkinson's disease.
AB  - BACKGROUND: Recent studies have suggested a relation between statin use and the
      risk of Parkinson's disease (PD). However, the conclusions are inconsistent. Some
      studies found an increased incidence of PD among statin users; others found a
      decreased incidence. Others showed that PD incidence was related to baseline
      cholesterol levels. OBJECTIVES: To examine the association between baseline
      levels of low-density lipoprotein cholesterol (LDL-C), long-term statin use, and
      the incidence of PD. METHODS: The study group consisted of a historical cohort of
      94,308 men and women in Israel aged 45 years or more without PD or statin use at
      baseline, between 2000 and 2007. PD incidence among long-term statin users was
      compared with that among nonusers. The cohort was divided into 4 groups according
      to baseline LDL-C levels, and their relative risks of developing PD were
      calculated with adjustment for potential confounders (sex, age, socioeconomic
      status, history of ischemic heart disease, hypertension, stroke, and smoking).
      The association between different variables was analyzed with a Cox proportional
      hazards model. RESULTS: During the study period, 1035 incident cases of PD were
      identified. Statin use was associated with a significant decrease in the
      incidence of PD (odds ratio, 0.73, 95% confidence interval, 0.60-0.88; P=.001).
      No association was found between baseline LDL-C levels and PD risk. CONCLUSIONS:
      Our results provide additional evidence regarding the lower incidence of PD among
      statin users. These findings warrant further research regarding the possible
      neuroprotective role of statins in PD and other neurodegenerative diseases.

PMID- 24304213
TI  - Potential misuse and inappropriate prescription practices involving opioid
      analgesics.
AB  - BACKGROUND: Opioid misuse and abuse are growing concerns among the medical and
      public health communities. OBJECTIVES: To examine the prevalence of indicators
      for potential opioid misuse in a large, commercially insured adult population.
      METHODS: We adapted existing indicators developed by expert panels to include
      having overlapping opioid prescriptions, overlapping opioid and benzodiazepine
      prescriptions, long-acting/ extended release (LA/ER) opioids for acute pain,and
      high daily doses of opioids (>100 morphine milligram equivalents). These
      indicators were assessed among continuously enrolled individuals aged 18-64 years
      from the 2009 Truven Health MarketScan databases. Analyses were stratified by
      sex. RESULTS: We identified 3,391,599 eligible enrollees who received at least 1
      opioid prescription. On average, enrollees obtained 3.3 opioid prescriptions, and
      the average annual days of supply was 47 days. Twice as many enrollees received
      opioid prescriptions for acute pain as for chronic pain. About a quarter of the
      enrollees had at least 1 indicator of either potential misuse by patients or
      inappropriate prescription practices by providers. About 15% of enrollees had
      high daily doses;7.8% had opioid overlap; and 7.9% had opioid and benzodiazepine
      overlap. Among those prescribed LA/ER opioids, 24.3% were treated for acute pain.
      Overlap indicators were more common among women. CONCLUSIONS: Our findings
      underscore the critical need to develop programs aimed at promoting appropriate
      use of opioids. Retrospective opioid utilization reviews similar to our analyses
      can potentially help managed care organizations and healthcare providers improve
      patient care and reduce the risk of adverse outcomes related to these
      medications.

PMID- 24304214
TI  - Does medication adherence lead to lower healthcare expenses for patients with
      diabetes?
AB  - OBJECTIVES: To examine the relationship between medication adherence and
      healthcare outcomes and expenses and to investigate whether the duration of type
      2 diabetes mellitus (T2DM) has a role in the aforementioned relationship. DATA
      SOURCE/STUDY SETTING: Health insurance claims data under a universal coverage
      system in Taiwan. STUDY DESIGN: Seven years of longitudinal analysis was
      performed to examine the association between medication adherence of oral
      antihyperglycemic drugs and outcomes among patients with newly diagnosed T2DM.
      Generalized estimating equations were conducted to assess the temporal
      relationship while controlling for unobserved characteristics of patients.
      RESULTS: Better medication adherence was associated with decreased
      hospitalization and emergency department (ED) visits for diabetes or related
      conditions. The results also revealed that medication adherence was negatively
      associated with the expenses of hospitalization and ED visits for diabetes or
      related conditions, but medication adherence was positively associated with
      patients' total healthcare expenses. However, the adherence-related differences
      in total healthcare expenses began to decrease 5 years after the time of diabetes
      onset. CONCLUSIONS: Adherence to medication can improve healthcare outcomes but
      is associated with higher total healthcare expenses, especially during the years
      immediately following the onset of diabetes. Long-term follow-up is needed for
      further investigation.

PMID- 24304215
TI  - False activation of the cardiac catheterization laboratory for primary PCI.
AB  - OBJECTIVES: We sought to evaluate trends in door-to-balloon (D2B) times and false
      activation rates for the cardiac catheterization laboratory (CCL) in patients
      presenting to the emergency department (ED) with acute ST-elevation myocardial
      infarction (STEMI). In patients with STEMI, national efforts have focused on
      reducing D2B times for primary percutaneous coronary intervention (P-PCI). This
      emphasis on time-to-treatment may increase the rate of false CCL activations and
      unnecessary healthcare utilization. STUDY DESIGN: Retrospective quality
      improvement chart review. METHODS: We examined all emergent CCL activations for P
      PCI between 2007 and 2011 at the University of Michigan Hospital. False
      activation was defined as emergent CCL activation when the patient did not
      require CCL care or emergent cardiology evaluation in the ED. Pre-hospital or ED
      false activation rates and mean D2B time were retrospectively determined by chart
      review. RESULTS: The CCL was activated 717 times for suspected STEMI. The number
      of CCL activations increased from 96 in 2007 to 190 in 2011. False CCL
      activations accounted for 28% of all prehospital and 29% of all ED activations.
      The false activation rate increased from 15% of all cases in 2007 to 40% of all
      cases in 2011. The median D2B time decreased from 67 minutes in 2007 to 55
      minutes in 2011. CONCLUSIONS: Over a 5-year period with a strong emphasis on
      reducing D2B times, there has been an increased CCL false activation rate for P
      PCI.

PMID- 24304216
TI  - Influence of soluble PEG-OH incorporation in a 3D cell-laden PEG-fibrinogen (PF)
      hydrogel on smooth muscle cell morphology and growth.
AB  - We have been able to control hydrogel compliance and cell spreading in a three
      dimensional (3D) cell-laden system (hydrogel) using soluble PEG-OH. This was
      accomplished by encapsulating smooth muscle cells (SMCs) into poly(ethylene
      glycol)-fibrinogen (PEG-fibrinogen or PF) with poly(ethylene glycol)-diol (PEG
      OH) as a macromolecular leachant. The cell-encapsulating hydrogels were prepared
      with three concentrations of soluble PEG-OH having a mass of 10 kDa (1, 5 and 10%
      w/v). Rheology was used to measure the elastic (storage) component of the complex
      shear modulus of these hydrogels, while quantitative morphometrics were used to
      characterize SMC morphology. PF hydrogel with a higher amount of PEG-OH displayed
      a lower storage modulus and a higher elongated cell morphology of SMCs.
      Structural changes of PF hydrogels mainly owing to gelation-induced phase
      separation imparted by the soluble PEG-OH in 3D cell-laden hydrogels dramatically
      affected both the properties of the hydrogel network including the modulus as
      well as cell spreading.

PMID- 24304217
TI  - Morphological changes of the hair roots in alopecia areata: a scanning electron
      microscopic study.
AB  - Alopecia areata is a chronic inflammatory condition causing non-scarring patchy
      hair loss. Diagnosis of alopecia areata is made by clinical observations, hair
      pluck test and dermoscopic signs. However, because differentiation from other
      alopecia diseases is occasionally difficult, an invasive diagnostic method using
      a punch biopsy is performed. In this study, to develop a reliable, less invasive
      diagnostic method for alopecia areata, we performed scanning electron microscopy
      of the hair roots of alopecia areata patients. This study identified four
      patterns of hair morphology specific to alopecia areata: (I) long tapering
      structure with no accumulation of scales; (II) club-shaped hair root with fine
      scales; (III) proximal accumulation of scales; and (IV) sharp tapering of the
      proximal end of hair. On the basis of these results, we can distinguish alopecia
      areata by scanning electron microscopic observation of the proximal end of the
      hair shafts. 

PMID- 24304218
TI  - Editorial comment to obese patients undergoing cystectomy: a population-based,
      propensity score matched analysis.

PMID- 24304219
TI  - Structure-activity relationship of adenosine 5'-diphosphoribose at the transient
      receptor potential melastatin 2 (TRPM2) channel: rational design of antagonists.
AB  - Adenosine 5'-diphosphoribose (ADPR) activates TRPM2, a Ca(2+), Na(+), and K(+)
      permeable cation channel. Activation is induced by ADPR binding to the cytosolic
      C-terminal NudT9-homology domain. To generate the first structure-activity
      relationship, systematically modified ADPR analogues were designed, synthesized,
      and evaluated as antagonists using patch-clamp experiments in HEK293 cells
      overexpressing human TRPM2. Compounds with a purine C8 substituent show
      antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very
      effective. Modification of the terminal ribose results in a weak antagonist,
      whereas its removal abolishes activity. An antagonist based upon a hybrid
      structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 MUM), is more potent than 8-Ph
      ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes
      activity, but replacement of the pyrophosphate and the terminal ribose by a
      sulfamate-based group leads to a weak antagonist, a lead to more drug-like
      analogues. 8-Ph-ADPR (5) inhibits Ca(2+) signalling and chemotaxis in human
      neutrophils, illustrating the potential for pharmacological intervention at
      TRPM2. 

PMID- 24304220
TI  - A comprehensive laboratory-based program for classification of variants of
      uncertain significance in hereditary cancer genes.
AB  - Genetic testing has the potential to guide the prevention and treatment of
      disease in a variety of settings, and recent technical advances have greatly
      increased our ability to acquire large amounts of genetic data. The
      interpretation of this data remains challenging, as the clinical significance of
      genetic variation detected in the laboratory is not always clear. Although
      regulatory agencies and professional societies provide some guidance regarding
      the classification, reporting, and long-term follow-up of variants, few protocols
      for the implementation of these guidelines have been described. Because the
      primary aim of clinical testing is to provide results to inform medical
      management, a variant classification program that offers timely, accurate,
      confident and cost-effective interpretation of variants should be an integral
      component of the laboratory process. Here we describe the components of our
      laboratory's current variant classification program (VCP), based on 20 years of
      experience and over one million samples tested, using the BRCA1/2 genes as a
      model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2
      variants of uncertain significance (VUSs) are detected to 2.1% in the absence of
      a pathogenic mutation, demonstrating how the coordinated application of resources
      toward classification and reclassification significantly impacts the clinical
      utility of testing. 

PMID- 24304222
TI  - Spontaneous peer conversation in preschoolers with high-functioning autism
      spectrum disorder versus typical development.
AB  - BACKGROUND: In typical development, early peer talk is crucial for pragmatic
      development. The pragmatic deficit, reflected in remarkably deficient
      conversational capabilities, is considered the hallmark of the language deficit
      in autism spectrum disorder (ASD); yet, spontaneous peer talk in preschoolers
      with ASD was rarely explored. METHOD: We conducted comparative assessment of
      spontaneous peer talk during 10-min free-play scenarios in preschoolers with high
      functioning ASD (HFASD; n = 27) versus those with typical development (n = 30).
      Groups were matched on SES, verbal/nonverbal MA, IQ, and CA. Correlations with
      CA, IQ, VMA, and NVMA were examined. We compared the two groups' interactions
      with a friend-partner versus a nonfriend partner; in addition, in the HFASD
      group, we examined interactions with a typical partner (mixed dyads) versus a
      partner with HFASD (nonmixed dyads). Children's conversations were videotaped and
      coded to tap pragmatic capabilities and conversational quality. RESULTS: Findings
      revealed group differences in pragmatic abilities and conversational quality,
      with the typical group showing more intact capacities than the HFASD group.
      However, in the HFASD group, interactions with friends surpassed interactions
      with nonfriends on several key pragmatic capabilities and on all conversational
      quality measures (meshing, assertiveness, and responsiveness), thus suggesting
      that friendship may enable children to converse in a more socially complex and
      coregulated way. Also, children with higher cognitive capabilities, especially in
      the HFASD group, demonstrated more intact pragmatic capacities. CONCLUSION:
      Despite the robust pragmatic deficit in HFASD, reflected in conversational
      capabilities, involvement in friendship relationships and high cognitive
      capabilities were linked to more intact pragmatic capacities. Theoretical and
      therapeutic implications are discussed.

PMID- 24304221
TI  - Higher order amyloid fibril structure by MAS NMR and DNP spectroscopy.
AB  - Protein magic angle spinning (MAS) NMR spectroscopy has generated structural
      models of several amyloid fibril systems, thus providing valuable information
      regarding the forces and interactions that confer the extraordinary stability of
      the amyloid architecture. Despite these advances, however, obtaining atomic
      resolution information describing the higher levels of structural organization
      within the fibrils remains a significant challenge. Here, we detail MAS NMR
      experiments and sample labeling schemes designed specifically to probe such
      higher order amyloid structure, and we have applied them to the fibrils formed by
      an eleven-residue segment of the amyloidogenic protein transthyretin (TTR(105
      115)). These experiments have allowed us to define unambiguously not only the
      arrangement of the peptide beta-strands into beta-sheets but also the beta-sheet
      interfaces within each protofilament, and in addition to identify the nature of
      the protofilament-to-protofilament contacts that lead to the formation of the
      complete fibril. Our efforts have resulted in 111 quantitative distance and
      torsion angle restraints (10 per residue) that describe the various levels of
      structure organization. The experiments benefited extensively from the use of
      dynamic nuclear polarization (DNP), which in some cases allowed us to shorten the
      data acquisition time from days to hours and to improve significantly the signal
      to-noise ratios of the spectra. The beta-sheet interface and protofilament
      interactions identified here revealed local variations in the structure that
      result in multiple peaks for the exposed N- and C-termini of the peptide and in
      inhomogeneous line-broadening for the residues buried within the interior of the
      fibrils. 

PMID- 24304223
TI  - Incidence, risk, and prevention of ventilator-associated pneumonia in adult
      cardiac surgical patients: a systematic review.
AB  - Ventilator-associated pneumonia remains a major cause of morbidity and mortality
      in postoperative heart surgery patients. We present a systematic review of the
      literature on the incidence, risk factors, and prevention of this condition in a
      population at heightened risk.

PMID- 24304224
TI  - Selective 4e-/4H+ O2 reduction by an iron(tetraferrocenyl)porphyrin complex: from
      proton transfer followed by electron transfer in organic solvent to proton
      coupled electron transfer in aqueous medium.
AB  - An iron porphyrin catalyst bearing four ferrocenes and a hydrogen bonding distal
      pocket is found to catalyze 4e(-)/4H(+) oxygen reduction reaction (ORR) in
      organic solvent under homogeneous conditions in the presence of 2-3 equiv of
      Trifluoromethanesulphonic acid. Absorption spectroscopy, electron paramagnetic
      resonance (EPR), and resonance Raman data along with H2O2 assay indicate that one
      out of the four electrons necessary to reduce O2 to H2O is donated by the ferrous
      porphyrin while three are donated by the distal ferrocene residues. The same
      catalyst shows 4e(-)/4H(+) reduction of O2 in an aqueous medium, under
      heterogeneous conditions, over a wide range of pH. Both the selectivity and the
      rate of ORR are found to be pH independent in an aqueous medium. The ORR proceeds
      via a proton transfer followed by electron transfer (PET) step in an organic
      medium and while a 2e(-)/1H(+) proton coupled electron transfer (PCET) step
      determines the electrochemical potential of ORR in an aqueous medium. 

PMID- 24304226
TI  - Maxillary sinus lateral wall thickness and morphologic patterns in the atrophic
      posterior maxilla.
AB  - BACKGROUND: The aim of the present study is to examine the sinus lateral wall
      thickness (LWT) of atrophic posterior maxilla (<10 mm) of patients with complete
      and partial edentulism and determine the influence of residual ridge height (RH),
      sex, and age on maxillary LWT. METHODS: Four hundred fourteen measures were taken
      from 140 consecutive patients that met the inclusion criteria. On the selected
      sagittal section, a built-in digital caliper recorded in millimeters the RH and
      LWT (a perpendicular line at 3, 5, 7, 10, 13, and 15 mm from the lowest point of
      the sinus floor). Edentulous spans were further classified as complete edentulous
      atrophic maxilla (CEM) and partial edentulous atrophic maxilla (PEM). The mixed
      linear model was used to test the effects of sex, type of edentulism, edentulous
      span, and RH on the measurement of the LWT of the sinus. RESULTS: Mean LWT for
      PEM was 1.71 +/- 0.12 mm, and for CEM, 1.57 +/- 0.07 mm (P = 0.01). The mixed
      model yielded significant effect of edentulous span (P = 0.048) and interactions
      among type of edentulism and edentulous span (P <0.001) and edentulous span by RH
      (P <0.01). Age and RH were positively associated with LWT; however, they did not
      interact with RH, sex, or type of edentulism. RH has been shown to correlate with
      edentulous span (P <0.001) and type of edentulism (P = 0.01). The longer the
      edentulous span, the thinner the LWT. Similarly, RH was larger for PEM (6.85 +/-
      0.34 mm) than CEM (5.69 +/- 0.26 mm). CONCLUSIONS: The maxillary sinus lateral
      wall tends to increase in thickness from the second premolar to the second molar
      and from 5 mm up to 15 mm. In addition, RH, presence of teeth adjacent to the
      edentulous atrophic ridge, and age were shown to influence maxillary sinus LWT.

PMID- 24304225
TI  - Gender-related changes of the epicardial fat thickness and leptin in obstructive
      sleep apnea.
AB  - BACKGROUND: Epicardial fat thickness (EFT), an indicator of visceral obesity, and
      leptin are 2 novel markers for studying the obstructive sleep apnea (OSA)
      population. This study aimed to investigate the effects of gender on leptin
      levels and EFT, and the relation with OSA severity. METHODS: A total of 149
      patients with OSA (female/male 55/94 and mean age 50.8 +/- 9.2 years) and 50
      control patients (female/male 24/26 and mean age 48.9 +/- 8.8 years) were
      included in the study. The study population was divided into 4 groups according
      to apnea/hypopnea index (AHI) as control (AHI <5), the mild OSA (AHI 5-14), the
      moderate OSA (AHI 15-29), and the severe OSA (AHI >=30). EFT was obtained from
      parasternal long-axis and parasternal short-axis echocardiographic images.
      RESULTS: Leptin levels among females were significantly higher than among males
      (10.5 [7.8] vs. 5.4 [4.5] ng/mL, P = 0.001, respectively). Among women, leptin
      levels were significantly higher in the severe OSA group compared to the control
      group (9.8 [9.0] vs. 15.5 [10.1] ng/mL, P = 0.05, respectively). Conversely, no
      relation was observed between OSA severity and the leptin levels among men. EFT
      was not significantly different between the 2 genders (P > 0.05). EFT was thicker
      in the severe OSA group than in the control and mild OSA groups among women,
      whereas EFT was not changed according to OSA severity among males (P > 0.05).
      CONCLUSION: Leptin and EFT may be a valuable parameter in the evaluation of OSA
      severity in women than in men.

PMID- 24304227
TI  - Tooth loss, periodontitis, and statins in a population-based follow-up study.
AB  - BACKGROUND: Statins, frequently prescribed in lipid-lowering therapies, seem to
      have additional beneficial effects on periodontitis and tooth loss. If this is
      true, then chronic treatment with statins should also result in diminished tooth
      loss as a long-term response. METHODS: A 5-year population-based follow-up study
      of tooth loss was performed comparing participants treated with statins (n = 134)
      with those not on the drugs (Study of Health in Pomerania). Negative binomial
      regression models were used to analyze the count variable of the outcome,
      including risk factors for tooth loss and measures of cholesterol metabolism.
      RESULTS: When adjusted for age and sex, statins were associated with reduced
      tooth loss during the follow-up period (incidence risk ratio [IRR] = 0.70, 95%
      confidence interval [CI] = 0.50 to 0.99, P = 0.04). When additionally adjusted
      for risk factors of periodontal breakdown, IRR was 0.72 (95% CI = 0.52 to 1.01).
      There was significant interaction with low-density lipoprotein cholesterol (LDL
      c) at baseline. After stratification by LDL-c, statins were associated with
      reduced tooth loss, resulting in IRR = 0.89 (95% CI = 0.44 to 1.83) and 0.64 (95%
      CI = 0.43 to 0.95), P = 0.03, at LDL-c concentrations <=100 mg/dL and >100 mg/dL
      (2.58 mmol/L), respectively. The data also showed reduced tooth loss associated
      with the 5-year reduction in LDL-c levels on a mmol/L basis and independently of
      statins (IRR = 0.87, 95% CI = 0.80 to 0.96, P = 0.004). CONCLUSION: Long-term
      treatment with systemically administered statins may have the beneficial effect
      of protecting against tooth loss.

PMID- 24304229
TI  - Australian parents' experiences of speech generating device (SGD) service
      delivery.
AB  - OBJECTIVE: To explore parents' perceptions of existing support for families with
      a new speech generating device (SGD). METHOD: Six Australian parents of school
      aged children who used an SGD participated in semi-structured interviews about
      their experiences of SGD support. Data were explored and compared using narrative
      analysis. RESULTS: Participants discussed barriers to service access, including
      long waiting lists, service exclusion policies and limited therapist expertise in
      SGD practice. They emphasized the value of ongoing service coordination for
      families. Finally, participants discussed the nature of role boundaries and
      responsibilities for parents vs. therapists in the intervention process and the
      impact that intervention approaches had on parent autonomy, empowerment and
      confidence. CONCLUSION: Having an SGD at home generates ongoing support needs,
      which had not been well met for some parents in our study. Results suggest that
      timely, well coordinated and family-centred support may enhance service
      experience for families with a new device.

PMID- 24304228
TI  - Polymorphisms of EpCAM gene and prognosis for non-small-cell lung cancer in Han
      Chinese.
AB  - The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety
      of human cancers and is associated with patient prognosis, including those with
      lung cancer. However, the association of single nucleotide polymorphisms (SNPs)
      in the EpCAM gene with the prognosis for non-small-cell lung cancer (NSCLC)
      patients has never been investigated. We evaluated the association between two
      SNPs, rs1126497 and rs1421, in the EpCAM gene and clinical outcomes in a Chinese
      cohort of 506 NSCLC patients. The SNPs were genotyped using the Sequenom iPLEX
      genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier
      curves were used to assess the association of EpCAM gene genotypes with the
      prognosis of NSCLC. We found that the non-synonymous SNP rs1126497 was
      significantly associated with survival. Compared with the CC genotype, the CT+TT
      genotype was a risk factor for both death (hazard ratio, 1.40; 95% confidence
      interval [CI], 1.02-1.94; P = 0.040) and recurrence (hazard ratio, 1.34; 95% CI,
      1.02-1.77; P = 0.039). However, the SNP rs1421 did not show any significant
      effect on patient prognosis. Instead, the AG+GG genotype in rs1421 was
      significantly associated with early T stages (T1/T2) when compared with the AA
      genotype (odds ratio for late stage = 0.65; 95% CI, 0.44-0.96, P = 0.029).
      Further stratified analysis showed notable modulating effects of clinical
      characteristics on the associations between variant genotypes of rs1126497 and
      NSCLC outcomes. In conclusion, our study indicated that the non-synonymous SNP
      rs1126497 may be a potential prognostic marker for NSCLC patients.

PMID- 24304230
TI  - Prediction of road traffic death rate using neural networks optimised by genetic
      algorithm.
AB  - Road traffic injuries (RTIs) are realised as a main cause of public health
      problems at global, regional and national levels. Therefore, prediction of road
      traffic death rate will be helpful in its management. Based on this fact, we used
      an artificial neural network model optimised through Genetic algorithm to predict
      mortality. In this study, a five-fold cross-validation procedure on a data set
      containing total of 178 countries was used to verify the performance of models.
      The best-fit model was selected according to the root mean square errors (RMSE).
      Genetic algorithm, as a powerful model which has not been introduced in
      prediction of mortality to this extent in previous studies, showed high
      performance. The lowest RMSE obtained was 0.0808. Such satisfactory results could
      be attributed to the use of Genetic algorithm as a powerful optimiser which
      selects the best input feature set to be fed into the neural networks. Seven
      factors have been known as the most effective factors on the road traffic
      mortality rate by high accuracy. The gained results displayed that our model is
      very promising and may play a useful role in developing a better method for
      assessing the influence of road traffic mortality risk factors. 

PMID- 24304231
TI  - Effect of monoglyceride structure and cholesterol content on water permeability
      of the droplet bilayer.
AB  - The process of water permeation across lipid membranes has significant
      implications for cellular physiology and homeostasis, and its study may lead to a
      greater understanding of the relationship between the structure of lipid bilayer
      and the role that lipid structure plays in water permeation. In this study, we
      formed a droplet interface bilayer (DIB) by contacting two aqueous droplets
      together in an immiscible solvent (squalane) containing bilayer-forming
      surfactant (monoglycerides). Using the DIB model, we present our results on
      osmotic water permeabilities and activation energy for water permeation of an
      associated series of unsaturated monoglycerides as the principal component of
      droplet bilayers, each having the same chain length but differing in the position
      and number of double bonds, in the absence and presence of a varying
      concentration of cholesterol. Our findings suggest that the tailgroup structure
      in a series of monoglyceride bilayers is seen to affect the permeability and
      activation energy for the water permeation process. Moreover, we have also
      established the insertion of cholesterol into the droplet bilayer, and have
      detected its presence via its effect on water permeability. The effect of
      cholesterol differs depending on the type of monoglyceride. We demonstrate that
      the DIB can be employed as a convenient model membrane to rapidly explore subtle
      structural effects on bilayer water permeability. 

PMID- 24304232
TI  - Myocardial ischemia/reperfusion injury: potential of TRPV1 agonists as
      cardioprotective agents.
AB  - Myocardial Ischemia/Reperfusion (I/R) induced injury has widespread detrimental
      effects partially negating the benefits obtained from early revascularization in
      Acute Myocardial Infarction. Various complex mechanisms contribute to I/R injury
      and different agents targeting those specific mechanisms are being studied.
      Despite continued research and widespread interest, none of them have become
      incorporated into everyday practice. The TRPV1 (transient receptor potential
      vanilloid 1) channel is a non selective cation channel predominantly expressed in
      sensory neurons with the nerve fibers innervating the heart and blood vessels.
      Multiple studies have demonstrated the importance of the activation of TRPV1 and
      subsequent release of sensory neurotransmitters in cardioprotection. This review
      focuses on the role of TRPV1 in prevention of cardiac I/R injury, the work that
      has been done so far and future implications for TRPV1 agonists as
      cardioprotective agents. 

PMID- 24304233
TI  - Effects of Cichorium intybus linn on blood glucose, lipid constituents and
      selected oxidative stress parameters in streptozotocin-induced diabetic rats.
AB  - The efficacy of herbal medicine has been confirmed in treatment of diabetes
      mellitus (DM) by amelioration of oxidative stress. The present study was designed
      to investigate protective effects of Cichorium intybus extract (CIE) against
      oxidative damage in diabetic rats. In this study, the rats were divided into the
      control (C), diabetic (D), D + CIE- treated (125 mg/kg/day) groups. Male Sprague
      Dawley rats aged 9 weeks (160 +/- 15 g) were administered with streptozotocin
      (STZ, 60 mg/kg) intraperitoneally (ip) to induce experimental diabetes. From 3
      days after STZ administration to the end of the study (4 weeks) the ethanolic
      extract of CIE was administered (i.p) to diabetic rats. Body weight and blood
      glucose were measured weekly. At the end of the 4-week period, blood was drawn
      for biochemical assay, in order to determine the changes of cellular antioxidant
      defense system, serum oxidative damage and serum lipid were measured profile. CIE
      injection to diabetic rats resulted in significant reduction in blood glucose,
      triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol
      (LDL-C) levels and significant elevation high density lipoprotein cholesterol
      (HDL-C) level as well as increase in the body weight as compared with the rats
      treated with STZ alone. In the treated diabetic group, we also observed the
      significant increase in reduced glutathione (GSH), superoxide dismutase (SOD),
      glutathione-S-transferase (GST) and catalase (CAT) with decline in
      malondialdehyde (MDA) level compared with the non-treated diabetic group. These
      results suggest that the Cichorium intybus extract has antioxidant properties and
      prevents diabetes complications by modulation of oxidative stress system. 

PMID- 24304234
TI  - A review of dietary influences on cardiovascular health: part 1: the role of
      dietary nutrients.
AB  - BACKGROUND: Lifestyle modification, including diet, is a key strategy for
      prevention and regression of cardiovascular disease (CVD), a leading cause of
      death worldwide. Traditionally, the study of the relationship between diet and
      CVD has focused on the analysis of single nutrients, or foods, in relation to CVD
      risk. OBJECTIVE: In part one of this review, we present current epidemiologic and
      clinical evidence on nutrition and cardiovascular health with regards to specific
      foods and nutrients aimed at preventing CVD. METHODS: The Cochrane Library
      database between 2006 and 2012 was searched for studies on effects of dietary
      factors on cardiovascular health. DISCUSSION: Evidence is presented on soy
      protein, fats, fish, nuts, fruit, vegetables, electrolytes, vitamins, and
      carbohydrate including fibre, glycaemic index, and wholegrains. Evidence from
      specific foods underpins current dietary CVD prevention guidelines, that advise
      on replacing saturated with unsaturated fat, consuming carbohydrate foods that
      are wholegrain or of low glycaemic index, increased consumption of fruit,
      vegetables (particularly cruciferous), nuts, and oily fish. Other nutrients (such
      as soya protein, or reducing sodium intake) reduce CVD risk via favourable
      effects on disease contributors (such as LDL-cholesterol or blood pressure), but
      also infer/promote dietary change that impacts other nutrients (using less animal
      or processed foods, resulting in saturated fat reduction). The complexity and
      limitations of interpreting dietary epidemiologic studies is reviewed. With the
      general ineffectiveness of nutrient-based intervention, recently the shift has
      been towards the examination of associations between dietary patterns and
      cardiovascular health, which will be examined in the second part of this review.

PMID- 24304236
TI  - The fate of cell grafts for the treatment of Huntington's disease: the post
      mortem evidence.
AB  - The hope that cell transplantation therapies will provide an ideal treatment
      option for neurodegenerative diseases has been considerably revived with the
      remarkable advancements in genetic engineering towards active cell fate
      determination in vitro. However, for disorders such as Huntington's disease (HD),
      the challenges that we face are still enormous. This autosomal dominant genetic
      disorder leads, in part, to massive neuronal loss and severe brain atrophy which,
      despite the cell type used, cannot be easily repaired. And before large clinical
      trials are even considered, we must take a critical look at the outcomes of the
      pilot studies already available, not only from a clinical perspective but also by
      a careful assessment of what we can learn from the autopsies of HD patients who
      have undergone transplantation. In this review, we summarize and discuss the
      seven transplantation pilot trials that were initiated worldwide in HD patients
      more than a decade ago, with a particular emphasis on the post-mortem analyses of
      nine unique cases. Moreover, we describe a series of factors, both technical and
      related to patient selection, that we deem important to predict the outcome of
      cell grafts in HD therapy. 

PMID- 24304235
TI  - Functional magnetic resonance imaging (fMRI) response to alcohol pictures
      predicts subsequent transition to heavy drinking in college students.
AB  - BACKGROUND AND AIMS: Young adults show the highest rates of escalating drinking,
      yet the neural risk mechanisms remain unclear. Heavy drinkers show variant
      functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD)
      response to alcohol cues, which may presage increasing drinking. In this
      longitudinal study, we ascertained whether BOLD response to alcohol pictures
      predicted subsequent heavy drinking among college students. METHODS: Participants
      were 43 18-21-year-olds in the United States who underwent BOLD scanning and
      completed monthly substance use surveys over the following year. Participants
      were categorized according to baseline and follow-up drinking into 13
      continuously moderate drinkers, 16 continuously heavy drinkers and 14
      transitioners who drank moderately at baseline but heavily by follow-up. During
      fMRI scanning at baseline, participants viewed alcohol and matched non-alcohol
      beverage images. RESULTS: We observed group differences in alcohol cue-elicited
      BOLD response in bilateral caudate, orbitofrontal cortex, medial frontal
      cortex/anterior cingulate and left insula (clusters > 2619 ml, voxelwise F(2,40) 
      > 3.23, P < 0.05, whole-brain corrected P < 0.05), where transitioners
      hyperactivated compared with moderate and heavy drinkers (all Tukey P < 0.05).
      Exploratory factor analysis revealed a single brain network differentiating those
      who subsequently increased drinking. Exploratory regressions showed that,
      compared with other risk factors (e.g., alcoholism family history, impulsivity),
      BOLD response best predicted escalating drinking amount and alcohol-related
      problems. CONCLUSIONS: Neural response to pictures of alcohol is substantially
      enhanced among United States college students who subsequently escalate drinking.
      Greater cue-reactivity is associated with larger increases in drinking and
      alcohol-related problems, regardless of other baseline factors. Thus, neural cue
      reactivity could uniquely facilitate identifying individuals at greatest risk for
      future problematic drinking.

PMID- 24304237
TI  - A new benzopyran derivative from Pseuduvaria indochinensis Merr.
AB  - From the twigs and leaves of Pseuduvaria indochinensis Merr., a new benzopyran
      derivative, pseudindochin (1), was isolated together with three known compounds,
      oligandrol (2), (6E,10E)-isopolycerasoidol (3) and polycerasoidol (4). The
      structure of compound 1 was elucidated on the basis of extensive spectroscopic
      data interpretation, including 1D, 2D NMR, HR-ESI-MS, UV and IR. Moreover,
      compounds 1-4 were evaluated in vitro for their cytotoxic activities against HL
      60 and SMMC-7721 cell lines, but these compounds were essentially non-cytotoxic
      (IC50>30 MUg/mL).

PMID- 24304238
TI  - 8-Substituted O(6)-cyclohexylmethylguanine CDK2 inhibitors: using structure-based
      inhibitor design to optimize an alternative binding mode.
AB  - Evaluation of the effects of purine C-8 substitution within a series of CDK1/2
      selective O(6)-cyclohexylmethylguanine derivatives revealed that potency
      decreases initially with increasing size of the alkyl substituent. Structural
      analysis showed that C-8 substitution is poorly tolerated, and to avoid
      unacceptable steric interactions, these compounds adopt novel binding modes.
      Thus, 2-amino-6-cyclohexylmethoxy-8-isopropyl-9H-purine adopts a "reverse"
      binding mode where the purine backbone has flipped 180 degrees . This provided a
      novel lead chemotype from which we have designed more potent CDK2 inhibitors
      using, in the first instance, quantum mechanical energy calculations.
      Introduction of an ortho-tolyl or ortho-chlorophenyl group at the purine C-8
      position restored the potency of these "reverse" binding mode inhibitors to that
      of the parent 2-amino-6-cyclohexylmethoxy-9H-purine. By contrast, the
      corresponding 8-(2-methyl-3-sulfamoylphenyl)-purine derivative exhibited
      submicromolar CDK2-inhibitory activity by virtue of engineered additional
      interactions with Asp86 and Lys89 in the reversed binding mode, as confirmed by X
      ray crystallography. 

PMID- 24304239
TI  - From people-centered to person-centered services, and back again.

PMID- 24304240
TI  - Synthesis and characterization of oligodeoxyribonucleotides modified with 2'
      amino-alpha-L-LNA adenine monomers: high-affinity targeting of single-stranded
      DNA.
AB  - The development of conformationally restricted nucleotide building blocks
      continues to attract considerable interest because of their successful use within
      antisense, antigene, and other gene-targeting strategies. Locked nucleic acid
      (LNA) and its diastereomer alpha-L-LNA are two interesting examples thereof.
      Oligonucleotides modified with these units display greatly increased affinity
      toward nucleic acid targets, improved binding specificity, and enhanced enzymatic
      stability relative to unmodified strands. Here we present the synthesis and
      biophysical characterization of oligodeoxyribonucleotides (ONs) modified with 2'
      amino-alpha-L-LNA adenine monomers W-Z. The synthesis of the target
      phosphoramidites 1-4 is initiated from pentafuranose 5, which upon Vorbruggen
      glycosylation, O2'-deacylation, O2'-activation and C2'-azide introduction yields
      nucleoside 8. A one-pot tandem Staudinger/intramolecular nucleophilic
      substitution converts 8 into 2'-amino-alpha-L-LNA adenine intermediate 9, which
      after a series of nontrivial protecting-group manipulations affords key
      intermediate 15. Subsequent chemoselective N2'-functionalization and O3'
      phosphitylation give targets 1-4 in ~1-3% overall yield over 11 steps from 5. ONs
      modified with pyrene-functionalized 2'-amino-alpha-L-LNA adenine monomers X-Z
      display greatly increased affinity toward DNA targets (DeltaTm/modification up to
      +14  degrees C). Results from absorption and fluorescence spectroscopy suggest
      that the duplex stabilization is a result of pyrene intercalation. These
      characteristics render N2'-pyrene-functionalized 2'-amino-alpha-L-LNAs of
      considerable interest for DNA-targeting applications.

PMID- 24304241
TI  - General movements in genetic disorders: A first look into Cornelia de Lange
      syndrome.
AB  - The assessment of General Movements (GMs), i.e. age-specific motor patterns
      during the first months of life, has repeatedly proven to be a valuable tool to
      predict neurodevelopmental outcomes. Abnormal spontaneous GMs were found to be
      among the most reliable markers for cerebral palsy. To add to the knowledge of
      the abnormal early motor repertoire we analysed prospectively collected video
      recordings of a boy clinically diagnosed with Cornelia de Lange syndrome. The
      observed atypical GMs are a further step to disentangle early motor peculiarities
      in the light of the genetic impact on the developing brain. 

PMID- 24304242
TI  - Using nanoparticles to get the most out of antioxidants in food.

PMID- 24304243
TI  - Liposomes modified with p-aminophenyl-alpha-D-mannopyranoside: a promising
      delivery system in targeting the brain.

PMID- 24304247
TI  - Interview with Gert Storm.

PMID- 24304244
TI  - What is the potential of syndecan-4-targeted novel delivery technologies?

PMID- 24304248
TI  - pH-sensitive drug-delivery systems for tumor targeting.
AB  - Drug-delivery system responses to stimuli have been well investigated recently.
      As pH decrease is observed in most solid tumors, drug-delivery systems responsive
      to the slightly acidic extracellular pH environment of solid tumors have been
      developed as a general strategy for tumor targeting. Drug vehicles that are
      sensitive to acidic endosome/lysosome pH have been constructed for efficient drug
      release in tumor cells. This review explains the mechanisms of acidic pH in the
      tumor microenvironment and endocytic-related organelles, endosomes and lysosomes.
      Nanoparticle responses to acidic extracellular pH are discussed, along with
      approaches for improving tumor-specific therapy. Endosome/lysosome pH-triggered
      vehicles are reviewed, which achieve rapid drug release in tumor cells and
      overcome multidrug resistance. 

PMID- 24304249
TI  - Systemic delivery of biotherapeutics through the lung: opportunities and
      challenges for improved lung absorption.
AB  - The development of Exubera((r)) (inhaled insulin) has paved the way for
      consideration of future inhaled biotherapeutic products for systemic delivery.
      This route of drug delivery favors highly potent small peptides without self
      association and large proteins resistant to enzymatic degradation for high
      bioavailability, while likely resulting in transient therapeutic effects.
      Improved therapeutic benefits with a needle-free delivery, such as inhaled
      insulin, are also rational pursuits. Molecules and their formulations must be
      carefully chosen and designed to optimize the rates of lung absorption and
      nonabsorptive loss. Novel molecular or formulation approaches, for example,
      Technosphere((r)), Fc-/scFv-fusion protein, PEGylation, polymeric or lipid-based
      micro/nanoparticles and liposomes, offer opportunities to improve lung absorption
      and therapeutic duration of some biotherapeutics. Critical assessments are now
      essential as to their therapeutic benefits, safety, patient acceptance and market
      competition, as carried out for Exubera. 

PMID- 24304251
TI  - A critical appraisal of microemulsions for drug delivery: part I.
AB  - Microemulsions (MEs) are thermodynamically stable, optically transparent
      isotropic solutions of oil and water successfully formulated by using a
      combination of suitable surfactant and cosurfactant. While the selection of oil
      is based primarily on the solubility of drug in it, surfactant is generally
      selected on the basis of its hydrophilic-lipophilic balance value. MEs are
      characterized by ultra-low interfacial tension between the immiscible phases and
      offer the advantage of spontaneous formation, thermodynamic stability and ease of
      manufacture. The solubilization power of MEs for lipophilic, hydrophilic and
      amphiphilic solutes form a viable approach for enhancing bioavailability of
      hydrophobic drugs and percutaneous permeation of poorly permeable drugs, mainly
      due to the large area to volume ratio available for mass transfer. 

PMID- 24304253
TI  - Referring patients for telephone counseling to promote colorectal cancer
      screening.
AB  - OBJECTIVE: To determine the feasibility, acceptability, and outcomes of a
      telephone counseling intervention promoting colorectal cancer (CRC) screening
      when patients are referred for counseling by primary care providers (PCPs). STUDY
      DESIGN: Interventional cohort study with no formal control group. METHODS: PCPs
      in 3 practices were prompted to address CRC screening in patient encounters and,
      if appropriate, to recommend referral for telephone counseling. A telephone
      counselor called referred patients, made an appointment for a counseling call,
      and mailed an educational booklet to patients. Counseling included education
      about CRC and screening tests, motivational interviewing, barrier counseling, and
      facilitated referral for colonoscopy or mailing of a fecal occult blood testing
      kit. About 7 months following counseling, electronic records were searched for
      evidence of colonoscopy. RESULTS: PCPs addressed CRC screening with 1945
      patients, most of whom were up-to-date with CRC testing, recommended counseling
      referral to 362, and of these 180 (49.7%) accepted the referral. A total of 140
      (77.8%) of referred patients were contacted and 67 (37.2%) received counseling.
      After counseling 93.9% were planning on CRC screening compared with 54.6% at the
      beginning of the call. Of those planning a colonoscopy, 53.2% received one within
      7 months. CONCLUSIONS: Referring patients for telephone counseling to promote CRC
      screening may be feasible and acceptable to PCPs and to some patients, and may
      increase CRC screening. Further evaluation of the intervention may be warranted
      to compare the rate of screening associated with the intervention to rates
      related to usual care and to other interventions.

PMID- 24304250
TI  - Current progress on aptamer-targeted oligonucleotide therapeutics.
AB  - Exploiting the power of the RNAi pathway through the use of therapeutic siRNA
      drugs has remarkable potential for treating a vast array of human disease
      conditions. However, difficulties in delivery of these and similar nucleic acid
      based pharmacological agents to appropriate organs or tissues, remains a major
      impediment to their broad clinical application. Synthetic nucleic acid ligands
      (aptamers) have emerged as effective delivery vehicles for therapeutic
      oligonucleotides, including siRNAs. In this review, we summarize recent
      attractive developments in creatively employing cell-internalizing aptamers to
      deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and
      antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA
      chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA
      delivery. In addition, the challenges and future prospects of aptamer-targeted
      oligonucleotide drugs for clinical translation are further highlighted. 

PMID- 24304254
TI  - Improving BP control through electronic communications: an economic evaluation.
AB  - BACKGROUND: Web-based collaborative approaches to managing chronic illness show
      promise for both improving health outcomes and increasing the efficiency of the
      healthcare system. OBJECTIVE: Analyze the cost-effectiveness of the Electronic
      Communications and Home Blood Pressure Monitoring to Improve Blood Pressure
      Control (e-BP) study, a randomized controlled trial that used a patient-shared
      electronic medical record, home blood pressure (BP) monitoring, and web-based
      pharmacist care to improve BP control (<140/90 mm Hg). STUDY DESIGN: Incremental
      cost-effectiveness analysis conducted from a health plan perspective. METHODS:
      Cost-effectiveness of home BP monitoring and web-based pharmacist care estimated
      for percent change in patients with controlled BP and cost per mm Hg in diastolic
      and systolic BP relative to usual care and home BP monitoring alone. RESULTS: A
      1% improvement in number of patients with controlled BP using home BP monitoring
      and web-based pharmacist care-the e-BP program-costs $16.65 (95% confidence
      interval: 15.37- 17.94) relative to home BP monitoring and web training alone.
      Each mm HG reduction in systolic and diastolic BP achieved through the e-BP
      program costs $65.29 (59.91-70.67) relativeto home BP monitoring and web tools
      only. Life expectancy was increased at an incremental cost of $1850 (1635-2064)
      and $2220 (1745-2694) per year of life saved for men and women, respectively.
      CONCLUSIONS: Web-based collaborative care can be used to achieve BP control at a
      relatively low cost. Future research should examine the cost impact of potential
      long-term clinical improvements.

PMID- 24304255
TI  - Risk-stratification methods for identifying patients for care coordination.
AB  - BACKGROUND: Care coordination is a key component of the patient-centered medical
      home. However, the mechanism for identifying primary care patients who may
      benefit the most from this model of care is unclear. OBJECTIVES: To evaluate the
      performance of several risk-adjustment/stratification instruments in predicting
      healthcare utilization. STUDY DESIGN: Retrospective cohort analysis. METHODS: All
      adults empaneled in 2009 and 2010 (n = 83,187) in a primary care practice were
      studied. We evaluated 6 models: Adjusted Clinical Groups (ACGs), Hierarchical
      Condition Categories (HCCs), Elder Risk Assessment, Chronic Comorbidity Count,
      Charlson Comorbidity Index, and Minnesota Health Care Home Tiering. A seventh
      model combining Minnesota Tiering with ERA score was also assessed. Logistic
      regression models using demographic characteristics and diagnoses from 2009 were
      used to predict healthcare utilization and costs for 2010 with binary outcomes
      (emergency department [ED] visits, hospitalizations, 30-day readmissions, and
      highcost users in the top 10%), using the C statistic and goodness of fit among
      the top decile. RESULTS: The ACG model outperformed the others in predicting
      hospitalizations with a C statistic range of 0.67 (CMS-HCC) to 0.73. In
      predicting ED visits, the C statistic ranged from 0.58 (CMSHCC) to 0.67 (ACG).
      When predicting the top 10% highest cost users, the performance of the ACG model
      was good (area under the curve = 0.81) and superior to the others. CONCLUSIONS:
      Although ACG models generally performed better in predicting utilization, use of
      any of these models will help practices implement care coordination more
      efficiently.

PMID- 24304256
TI  - Out-of-pocket costs and prescription reversals with oral linezolid.
AB  - OBJECTIVE: To determine the relationship between benefit design, out-of-pocket
      costs, and prescription reversals, and the impact of reversals on
      rehospitalizations and total healthcare costs among Medicare members prescribed
      oral linezolid. STUDY DESIGN: Medicare members from a national health plan
      prescribed oral linezolid posthospitalization for skin and soft tissue infection
      (SSTI) or pneumonia were followed retrospectively. METHODS: Members were
      identified by an oral linezolid prescription between June 1, 2007, and April 30,
      2011, where the index event was a prescription fill or reversal less than 2 days
      before or 10 days after discharge. Associations between out-of-pocket costs and
      reversal, and between reversal and rehospitalization 30 days postindex, were
      compared for prescription fills versus reversals. A generalized linear model
      calculated adjusted total healthcare costs per member controlling for age, sex,
      geographic region, and clinical characteristics. RESULTS: Reversal rates rose
      progressively from 2% for members with out-of-pocket costs of $0 to 27% for
      members with out-of-pocket costs higher than $100 (P < .0001). Infection-related
      rehospitalizations were 23% versus 9% for members with a prescription reversal
      versus a fill (P < .0001). While postdischarge prescription drug costs were
      $1228.78 lower (P <.0001), adjusted mean medical costs were $2061.69 higher (P =
      .0033) and total healthcare costs were $1280.93 higher (P = .0349) for reversal
      versus fill members. CONCLUSIONS: Higher out-of-pocket costs were associated with
      higher rates of reversal, and reversals were associated with higher rates of
      rehospitalization and adjusted total healthcare costs among Medicare members
      prescribed oral linezolid posthospitalization for SSTI or pneumonia.

PMID- 24304257
TI  - FDA warning and removal of rosiglitazone from VA national formulary.
AB  - OBJECTIVES: To describe changes in rosiglitazone prescribing following the US
      Food and Drug Administration (FDA) warning of potentially increased risk of
      myocardial infarction and removal from the Department of Veterans Affairs
      National Formulary (VANF), assess patient-level factors associated with
      rosiglitazone discontinuation, and evaluate changes in glucose control. STUDY
      DESIGN: Historical cohort. METHODS: Veterans with an active outpatient
      prescription for rosiglitazone on April 1, 2007, were followed until June 30,
      2008. Incidence rate ratios (IRRs) of rosiglitazone discontinuation were compared
      over time using Poisson methods. We identified patient-level factors associated
      with stopping rosiglitazone using multivariable Poisson regression and compared
      glycated hemoglobin (A1C) values across time among patients who
      discontinued/continued rosiglitazone using linear mixed models. RESULTS: Of
      95,539 veterans with an active outpatient rosiglitazone prescription, 86.7%
      discontinued rosiglitazone. Discontinuation rates increased significantly after
      the FDA warning, with IRRs from 1.6 to 1.8. After removal from the VANF,
      rosiglitazone discontinuation rates again increased significantly. Discontinuing
      rosiglitazone was associated with the FDA warning, removal from the VANF, female
      sex, black race, Hispanic ethnicity, comorbidity, A1C greater than 9%, and use of
      rosiglitazone as first- or second-line therapy. Among patients who did and did
      not receive a replacement medication, the mean changes in A1C from baseline were
      0.12% and 0.46%, respectively. For those who continued rosiglitazone, the mean
      change in A1C was -0.02%. CONCLUSION: The rosiglitazone discontinuation rate
      increased following the FDA warning and increased further following removal of
      rosiglitazone from the VANF. Glucose control may have declined among those who
      discontinued rosiglitazone.

PMID- 24304258
TI  - Emerging and encouraging trends in e-prescribing adoption among providers and
      pharmacies.
AB  - OBJECTIVE: The objective of this study is to describe the growth in provider
      (physician, nurse practitioner, and physician assistant) adoption of e
      prescribing and the growth in pharmacies actively accepting e-prescriptions using
      nationally representative data from December 2008 to December 2012. Additionally,
      this study explored e-prescribing adoption variation by urban and rural counties.
      STUDY DESIGN: Descriptive analysis of nationally representative, transactional e
      prescribing data. METHODS: Data for this analysis were from Surescripts.
      Surescripts is a leading e-prescription network utilized by a majority of all
      chain, franchise, or independently owned pharmacies in the United States routing
      prescriptions for more than 240 million patients through their network. RESULTS:
      The total number of prescribers, including physicians, nurse practitioners, and
      physician assistants e-prescribing via an electronic health record (EHR) on the
      Surescripts network has increased from 7% to 54%. Additionally, the number of
      pharmacies actively accepting e-prescriptions is 94%. These increases in
      pharmacies actively accepting e-prescriptions and the provider's eprescribing
      mirror the increase in the volume of e-prescriptions sent on the Surescripts
      network. CONCLUSIONS: This analysis shows that the vast majority of pharmacies in
      the United States are able to accept e-prescriptions and over half of providers
      are e-prescribing via an EHR.

PMID- 24304259
TI  - Team-based learning and ethics education in nursing.
AB  - This report describes the use of team-based learning concepts in an undergraduate
      nursing applied ethics course using established reporting guidelines. Team-based
      learning relies on actively engaging students in the learning process through
      small-group activities that facilitate the development of skills, including
      concept analysis, critical thinking, and problem solving. Students are divided
      into teams of five to seven members who collaborate throughout the semester to
      work through activities that build on ethics concepts introduced through reading
      and lectures. Nurse educators are challenged to develop educational approaches
      that will engage students and help them to apply what they learn from the study
      of ethics to the lived experience of clinical practice. The ultimate goal is to
      help students to develop into morally sensitive and competent professionals. Team
      based learning represents a novel way to teach these skills to undergraduate
      nursing students.

PMID- 24304260
TI  - Partnering to provide a summer institute of nursing.
AB  - With national projections indicating the need for more RNs to meet the health
      care workforce demands, innovative strategies to recruit high school students
      into the profession of nursing must be utilized. This article describes an
      innovative strategy aimed at high school students through a Summer Institute of
      Nursing--a 5-day, 4-night, college-based experience--designed to allow them the
      opportunity to explore the profession of nursing. Through skills laboratories,
      service projects, and health care site visits, students were able to experience
      the profession of nursing hands on. Based on the research conducted through pre-
      and post-surveys, the high school students experienced a significant change in
      their likelihood of pursuing a career in nursing after completing the Institute
      (p < 0.001). The format of the Summer Institute of Nursing represents an
      innovative strategy to recruit high school students into the profession of
      nursing.

PMID- 24304261
TI  - Use of the 5E learning cycle model combined with problem-based learning for a
      fundamentals of nursing course.
AB  - The 5E learning cycle model has shown a positive effect on student learning in
      science education, particularly in courses with theory and practice components.
      Combining problem-based learning (PBL) with the 5E learning cycle was suggested
      as a better option for students' learning of theory and practice. The purpose of
      this study was to compare the effects of the traditional learning method with the
      5E learning cycle model with PBL. The control group (n = 78) was subjected to a
      learning method that consisted of lecture and practice. The experimental group (n
      = 83) learned by using the 5E learning cycle model with PBL. The results showed
      that the experimental group had significantly improved self-efficacy, critical
      thinking, learning attitude, and learning satisfaction. Such an approach could be
      used in other countries to enhance students' learning of fundamental nursing.

PMID- 24304262
TI  - Developing standardized patient clinical simulations to apply concepts of
      interdisciplinary collaboration.
AB  - Interdisciplinary collaboration and interprofessional education (IPE) are
      essential for transforming health care. Students in nurse practitioner (NP)
      programs have limited exposure to IPE. Simulated clinical experiences, based on
      social learning theory, provide a safe and realistic environment to expose NP
      students to interdisciplinary collaboration as a step toward developing IPE.
      Faculty at a large university school of nursing developed a formative
      standardized patient experience to provide NP students with two opportunities to
      synthesize a patient assessment, to share patient problem-solving strategies, and
      to succinctly communicate with other health care professionals. This pilot
      project provided insight to better develop IPE and identified a growing interest
      to collaborate in future projects with faculty from other health care
      disciplines.

PMID- 24304263
TI  - Editorial comment to prediction of partial nephrectomy outcomes by using the
      diameter-axis-polar nephrometry score.

PMID- 24304265
TI  - The use of ionising radiation for the purpose of arresting external haemorrhage
      from an intracranial mass lesion.
AB  - External bleeding from any form of tumour of the central nervous system is
      unusual. We present a case where this difficult problem was controlled by the use
      of Gamma Irradiation from a focused delivery system.

PMID- 24304264
TI  - Wavelength-selective one- and two-photon uncaging of GABA.
AB  - We have synthesized photolabile 7-diethylamino coumarin (DEAC) derivatives of
      gamma-aminobutyric acid (GABA). These caged neurotransmitters efficiently release
      GABA using linear or nonlinear excitation. We used a new DEAC-based caging
      chromophore that has a vinyl acrylate substituent at the 3-position that shifts
      the absorption maximum of DEAC to about 450 nm and thus is named "DEAC450".
      DEAC450-caged GABA is photolyzed with a quantum yield of 0.39 and is highly
      soluble and stable in physiological buffer. We found that DEAC450-caged GABA is
      relatively inactive toward two-photon excitation at 720 nm, so when paired with a
      nitroaromatic caged glutamate that is efficiently excited at such wavelengths, we
      could photorelease glutamate and GABA around single spine heads on neurons in
      brain slices with excellent wavelength selectivity using two- and one-photon
      photolysis, respectively. Furthermore, we found that DEAC450-caged GABA could be
      effectively released using two-photon excitation at 900 nm with spatial
      resolution of about 3 MUm. Taken together, our experiments show that the DEAC450
      caging chromophore holds great promise for the development of new caged compounds
      that will enable wavelength-selective, two-color interrogation of neuronal
      signaling with excellent subcellular resolution. 

PMID- 24304266
TI  - Patent foramen ovale closure prior to surgery in the sitting position.
AB  - Previously, patent foramen ovale (PFO) was an absolute contraindication to
      surgery in the sitting position. We report two patients with PFO who underwent
      surgery in the sitting position after percutaneous PFO closure. To our knowledge
      this is the first report of this technique.

PMID- 24304267
TI  - The graft kinking of high-flow bypass for internal carotid artery aneurysm due to
      elongated styloid process: a case report.
AB  - Elongated styloid process is an often-caused symptom due to the compression of
      neighboring structures. We present a case of a graft kink of high-flow bypass due
      to an elongated styloid process and describe the technical pitfalls encountered
      when creating a graft route from the standpoint of the anatomical site.

PMID- 24304268
TI  - Air-embolism and cerebral ischaemia following epidural hydrogen peroxide
      irrigation in a closed lumbar cavity.
AB  - Authors report a case of air-embolism and subsequent ischaemic damage to the
      brain following intra-operative irrigation with hydrogen peroxide within a closed
      cavity of a spinal cold abscess of tuberculous origin. Copious amount of
      undiluted hydrogen peroxide irrigation was deployed under moderate pressure to
      clean-up the abscess cavity. Post-operatively, the patient developed seizures
      followed by clinical and radiological features of brain ischaemia ultimately
      resulting in a fatal outcome. The authors reflect on the events, review the
      relevant literature regarding intra-operative use of hydrogen peroxide in cranio
      spinal procedures, outline mechanism of its actions, and highlight its
      disadvantages and potential complications.

PMID- 24304269
TI  - New conservation is true conservation.

PMID- 24304270
TI  - Regulatory variant of the TPH2 gene and early life stress are associated with
      heightened attention to social signals of fear in infants.
AB  - BACKGROUND: Cross-species evidence suggests that genetic and experiential factors
      act early in development to establish individual emotional traits, but little is
      known about the mechanisms that emerge during this period to mediate long-term
      outcomes. Here, we tested the hypothesis that known genetic and environmental
      risk conditions may heighten infants' natural tendency to attend to threat
      alerting stimuli, resulting in a cognitive bias that may contribute to emotional
      vulnerability. METHODS: Data from two samples of 5-7-month-old infants (N = 139)
      were used to examine whether established candidate variations in the serotonin
      system genes, i.e., TPH2 SNP rs4570625 (-703 G/T) and HTR1A SNP rs6295 (-1019
      G/C), and early rearing condition (maternal stress and depressive symptoms) are
      associated with alterations in infants' attention to facial expressions. Infants
      were tested with a paradigm that assesses the ability to disengage attention from
      a centrally presented stimulus (a nonface control stimulus or a neutral, happy,
      or fearful facial expression) toward the location of a new stimulus in the visual
      periphery (a geometric shape). RESULTS: TPH2 -703 T-carrier genotype (i.e., TT
      homozygotes and heterozygotes), presence of maternal stress and depressive
      symptoms, and a combination of the T-carrier genotype and maternal depressive
      symptoms were associated with a relatively greater difficulty disengaging
      attention from fearful facial expressions. No associations were found with
      infants' temperamental traits. CONCLUSIONS: Alterations in infants' natural
      attentional bias toward fearful facial expressions may emerge prior to the
      manifestation of emotional and social behaviors and provide a sensitive marker of
      early emotional development.

PMID- 24304273
TI  - Drug discovery for infectious agents causing neglected diseases.

PMID- 24304272
TI  - The redox systems of Plasmodium falciparum and Plasmodium vivax: comparison, in
      silico analyses and inhibitor studies.
AB  - Plasmodium falciparum is responsible for the most severe form of human malaria.
      P. vivax, in contrast, is the most widespread malaria parasite with an enormous
      impact on health and economy, since the infection is characterized by high rates
      of relapses. Due to the mild course of malaria tertiana and complicated in vitro
      culturing conditions of P. vivax, most of the research on malaria parasites has
      focused on P. falciparum so far. The redox metabolism of P. falciparum is a
      promising target for novel antimalarial drugs, since maintaining a redox
      equilibrium is of fundamental importance for the parasite. P. falciparum contains
      a cytosolic glutathione and thioredoxin system, as well as redox systems in the
      apicoplast and the mitochondrion. In contrast to P. falciparum, little is known
      about the redox processes in P. vivax so far. This review summarizes the current
      knowledge of the redox metabolism in malaria parasites and provides a detailed in
      silico comparison of the known and mostly well characterized redox enzymes from
      P. falciparum and the largely unknown redox proteins from P. vivax. Known
      antimalarials at least partially mediating their antiparasitic activity by
      influencing the redox balance of Plasmodium, including dehydroepiandrosterone,
      Mannich bases, methylene blue, and naphthoquinones, are discussed. Furthermore,
      we present novel inhibitors identified via screening of a compound library from
      the Leibniz Institute for Natural Product Research and Infection Biology, Jena
      that are active against the redox-related enzymes thioredoxin reductase,
      glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate
      dehydrogenase 6- phosphoglucono- lactonase from P. falciparum. 

PMID- 24304274
TI  - The role of neuroendocrine cells in prostate cancer: a comprehensive review of
      current literature and subsequent rationale to broaden and integrate current
      treatment modalities.
AB  - Neuroendocrine prostate carcinoma (NE-PCa) is a heterogeneous disease. Due to a
      high prevalence of NE (neuroendocrine) differentiation in patients who receive
      prolonged androgen deprivation treatment, the real incidence of NE-PCa remains
      unknown. Similarly, the biological steps from prostate carcinoma (PCa) toward NE
      differentiation are far less than definitive and, consequently, there is a lack
      of evidence to support any of the treatments as the "gold standard". MATERIALS
      AND METHODS: A systematic literature search was conducted using the PubMed,
      Scopus, and Embase databases to identify original articles and review articles
      regarding NE-PCa . Keywords were "prostate cancer" and "neuroendocrine". Articles
      published between 1995 and 2013, were reviewed and selected with the consensus of
      all of the authors. RESULTS: Fifty-one articles were selected by the authors for
      the purpose of this review. The principle findings were reported into some
      subsections: Epidemiology, Biological steps of NE differentiation (with some
      principle articles on animal and in vitro, since there is very little in the
      literature on human studies); for the treatment options, we had to expand the
      search on PubMed to a larger timeframe and selection since very little was
      specifically found in the first criteria: surgery, radiotherapy, ablative
      techniques, immunomodulation and epigenetic therapy were then reviewed. A
      multidisciplinary approach, advocated by many authors, although promising, has
      failed to demonstrate increased survival rates. Limitations of this review
      include the lack of a clear definition of NE-PCa and consequently, the lack of
      strong evidence provided by a large series with long-term follow-up. CONCLUSIONS:
      Supported from this extensive review, we propose it is worthwhile to investigate
      a new multimodal therapeutic approach to address advanced NE-PCa starting from a
      debulking (with radical intent) of the disease plus epigenetic therapy with stem
      cell differentiation stage factors (SCDSFs). In addition immunotherapy can be
      used to treat the cancer presenting phenotype in association with chemomodulation
      plus ablative therapies, in case of advanced or recurrent diseases. SCDSFs may be
      utilized to regulate cancer stem cells and possible new phenotypes could also be
      associated with ablative therapies. Hormonal deprivation, radiotherapy,
      chemotherapy, ex vivo vaccines and targeted therapies could also be used and
      reserved in case of failure.

PMID- 24304275
TI  - A systemic approach to cancer treatment: tumor cell reprogramming focused on
      endocrine-related cancers.
AB  - The term "cancer cell reprogramming" is used to define any kind of intervention
      aimed at transforming cancer cells into terminally differentiated cells. Using
      this approach, new technologies have been applied with different methods for a
      more systemic approach to cancer treatment. This review reports on advances of
      these technologies, including our personal contributions, mainly carried out on
      endocrine-related cancers. Some of the interventions, aimed at reverting cancer
      cells into a normal phenotype, are based on the evidence that tumor development
      is suppressed by the embryonic microenvironment. On the basis of this rationale,
      experiments have been conducted using stem cell differentiation stage factors
      (SCDSFs) taken at different stages of development of Zebrafish embryos, oocyte
      extracts, or naive human umbilical cord matrix derived stem cells (UMDSCs).
      SCDSFs induce significant growth inhibition on different tumor cell lines in
      vitro, likely because of increases in cell cycle regulatory molecules, such as
      p53 and pRb. Treatment with these factors activates apoptosis and differentiation
      related to caspase-3. This is achieved via p73 apoptotic-dependent pathway
      activation with a concurrent normalization of the E-cadherin and beta-catenin
      ratio. Extracts from prophase amphibian oocytes could reprogram relevant
      epigenetic alterations in MCF-7 and HCC1954 breast cancer cell lines, while un
      engineered (naive) human UMDSCs attenuated growth of MDA-231 human breast
      carcinoma cells. A product prepared for human treatments, containing SCDSFs at
      very low doses, yielded favorable results in breast cancer and in intermediate
      advanced hepatocellular carcinoma. Other reprogramming interventions used in the
      models of breast, prostate and ovarian cancer cell lines are described. Finally,
      current and future perspectives of this novel technology are discussed and a new
      hallmark of cancer is suggested: the loss of differentiation of cancer cells. 

PMID- 24304271
TI  - Exogenous hormonal regulation in breast cancer cells by phytoestrogens and
      endocrine disruptors.
AB  - Observations on the role of ovarian hormones in breast cancer growth, as well as
      interest in contraception, stimulated research into the biology of estrogens. The
      identification of the classical receptors ERalpha and ERbeta and the
      transmembrane receptor GPER and the resolution of the structure of the ligand
      bound to its receptor established the principal molecular mechanisms of estrogen
      action. The presence of estrogen-like compounds in many plants used in
      traditional medicine or ingested as food ingredients, phytoestrogens, as well as
      the estrogenic activities of many industrial pollutants and pesticides,
      xenoestrogens, have prompted investigations into their role in human health.
      Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity
      than the endogenous estrogens and can compete or substitute the hormone.
      Xenoestrogens, which accumulate in the body throughout life, are believed to
      increase breast cancer risk, especially in cases of prenatal and prepuberal
      exposure whereas the role of phytoestrogens is still a matter of debate. At
      present, the application of phytoestrogens appears to be limited to the treatment
      of post-menopausal symptoms in women where the production of endogenous estrogens
      has ceased. In this review we discuss chemistry, structure and classification,
      estrogen signaling and the consequences of the interactions of estrogens,
      phytoestrogens and xenoestrogens with their receptors, the complex interactions
      of endogenous and exogenous ligands, the evaluation of the health risks related
      to xenoestrogens, and the perspectives toward the synthesis of potent third
      generation selective estrogen receptor modulators (SERMs). 

PMID- 24304276
TI  - Interlinking of hypoxia and estrogen in thyroid cancer progression.
AB  - Estrogen aids in neo-vascularization of various tumors during hypoxic conditions,
      however the role of estrogen within the hypoxic environment of thyroid cancer is
      not known. In a series of experimentations, using human thyroid cancer cells, we
      observed that estrogen and hypoxia modulate the hypoxia inducible factor-1 (HIF
      1) signaling which is abrogated by the anti-estrogen fulvestrant and the HIF-1
      inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole). Furthermore, we
      found that the conditioned medium from estrogen treated thyroid cancer cells lead
      to enhanced migration and tubulogenesis of human umbilical vein endothelial cells
      (HUVECs) which is abrogated by HIF-1 inhibitor. These findings, in addition to
      our previous and other scientific literature data, lead us to conclude that
      estrogen and hypoxia are interlinked in thyroid cancer and can equally modulate
      epithelial-endothelial cell interactions by mediating key cellular, metabolic and
      molecular processes of thyroid cancer progression. We believe that the hormonal
      component and cellular adaptation to oxygen tension of cancer cells are
      functionally equivalent with a cellular transition that can be exploited
      clinically for a combinational approach for thyroid cancer treatment involving
      antiestrogens as well as anti-hypoxic agents. 

PMID- 24304277
TI  - Changing the endocrine dependence of breast cancer: data and hypotheses.
AB  - Among the most common human cancers, often only breast and prostate cancers have
      advantage of hormone dependence. For a long time, this advantage permitted breast
      cancer to be efficaciously managed in the adjuvant and metastatic settings with
      low side effects by endocrine therapy. Unfortunately, soon or afterward hormone
      dependence is lost in most patients. In breast cancer, de novo or acquired
      hormone resistance is an hot issue and the focus of endless debate. Although a
      lack of oestrogen receptors (ERs) is considered to be the main reason for de novo
      hormone resistance, many studies have been conducted and many different
      mechanisms have been hypothesised to account for acquired hormone resistance.
      Thus far, hormone resistance appears to be occasionally delayed or avoided in "in
      vivo" experiments. However, this finding did not have a significant benefit in
      current clinical practice. The principal aim of this review article is to sum up
      and update the issue of changing the endocrine dependence of breast cancer.
      Recent molecular insights extensively elucidating and shedding new light on this
      very controversial issue are considered. Moreover, based on our recent reports, a
      new mechanistic interpretation of and a therapeutic approach for overcome hormone
      resistance are proposed. 

PMID- 24304278
TI  - The neuroendocrine component in bladder tumors.
AB  - Neoplastic urothelium has the capacity to display enormous plasticity and
      divergent differentiation. Neuroendocrine tumors arise as a result of such
      capacity. Neuroendocrine tumors of the bladder represent a limited number of
      neoplasms characterized by neuroendocrine hormone secretion and a poor outcome.
      These tumors can be displayed as pure neuroendocrine neoplasms or more frequently
      as a neuroendocrine counterpart mixed with classical urothelial bladder cell
      carcinomas, adenocarcinoma, sarcomatoid carcinoma or mixtures of these
      components. Their heterogeneous character and clinical aggressiveness remain a
      challenge for clinical, pathological diagnosis and for therapy selection. Several
      types have been described, although small cell carcinoma represents the major
      subgroup of neuroendocrine tumors as compared to large cell carcinoma and
      carcinoid subtypes. In this review, epidemiology, presentation, macroscopic and
      microscopic features, and clinical prognostic and therapeutic implications of the
      major subgroups are described. Special focus is given to discuss how
      immunohistochemistry protein patterns and laboratory determinations may aid to
      characterize this type of tumors and to improve the clinical management of this
      highly aggressive type of bladder cancer patients. 

PMID- 24304279
TI  - Neuroendocrine tumors of the lung: hystological classification, diagnosis,
      traditional and new therapeutic approaches.
AB  - Lung neuroendocrine tumors are neoplasms originating from bronchopulmonary
      neuroendocrine cells, usually Kulchitsky cells, loaded with argentaffin granules.
      They account for 20-25% of all primitive lung tumors, the most common being the
      small-cell undifferentiated carcinoma. They include different tumors, from tumors
      of low-grade malignancy, especially the typical carcinoids, with high survival
      rates after surgical therapy, to the high-grade malignancy tumors, especially
      small-cell undifferentiated carcinomas. The latter have very few indications for
      surgical treatment with a low survival rate, even after multimodal therapy. The
      aim of this review is to describe the present knowledge and discuss possible new
      developments in the management of pulmonary neuroendocrine tumors. The authors
      examine and discuss in particular the role that surgical techniques should have
      in the treatment of small-cell lung cancer in opposition to a nihilism position
      that has limited therapies to non-surgical approaches. The critical review of
      this attitude opens the door to a more aggressive approach. In the meantime the
      review shows that it might be possible to include the new minimally invasive
      percutaneous ablative techniques as cryosurgery, thermotherapy and irreversible
      electroporation within a modern and flexible framework. The authors also present
      the hypothesis that cancer stem cells (CSC) are at the basis of recurrences of
      small-cell lung cancer (SCLC) and therefore that the issue is of difficult
      solution with the conventional oncologic approach considering the chemo
      resistance of CSC to drugs. For these reasons an epigenetic therapy based on
      differentiation factors is proposed alongside the usual surgical and chemo
      radiation protocols. 

PMID- 24304280
TI  - Reprogramming cancer cells in endocrine-related tumors: open issues.
AB  - Reprogramming technologies have been developed to revert somatic differentiated
      cells into pluripotent stem cells that can be differentiated into different
      lineages potentially useful in stem cell therapy. Reprogramming methods have been
      progressively refined to increase their efficiency, to obtain a cell population
      suitable for differentiation, and to eliminate viral plasmid which could be
      responsible for many unwanted side-effects when used in personalized medicine.
      All these methods are aimed to introduce into the cell genes or mRNAs encoding a
      set of four transcription factors (OCT- 4, SOX-2, KLF-4 and c-MYC) or a set of
      three lincRNAs (large intragenic non-coding RNAs) acting downstream of the
      reprogramming transcription factors OCT-4, SOX-2 and NANOG. Translational
      clinical applications in human pathologies and in developmental, repair and
      cancer biology have been numerous. Cancer cells can be, at least in principle,
      reprogrammed into a normal phenotype. This is a recently raised issue, rapidly
      advancing in many human tumors, especially endocrine-related cancers, such as
      breast, prostate and ovarian ca. The present review aims to describe basic
      phenomena observed in reprogramming tumor cells and solid tumors and to discuss
      their meaning in human hormone-related cancers. We will also discuss the fact
      that some of the targeted transcription factors are "normally" activated in a
      number of physiological processes, such as morphogenesis, hypoxia and wound
      healing, suggesting an in vivo role of reprogramming for development and
      homeostasis. Finally, we will review concerns and warnings raised for in vivo
      reprogramming of human tumors and for the use of induced pluripotent stem cells
      (iPSCs) in human therapy. 

PMID- 24304281
TI  - Endocrine related cancer: from stem cells to new drug targets.

PMID- 24304282
TI  - Targeted therapy in advanced gastric carcinoma: the future is beginning.
AB  - Gastric cancer represents one of the most common cancer worldwide. Unfortunately,
      the majority of patients present in advanced stage and outcome still remains poor
      with high mortality rate despite decreasing incidence and new diagnostic and
      therapeutic strategies. Although utility of classical chemotherapy agents has
      been widely explored, advances have been slow and the efficacy of these agents
      has reached a plateau of median overall survival not higher than 12 months.
      Therefore, researchers focused their attention on better understanding molecular
      biology of carcinogenesis and deeper knowledge of the cancer cell phenotype, as
      well on development of rationally designed drugs that would target specific
      molecular aberrancies in signal transduction pathways. These targets include cell
      surface receptors, circulating growth and angiogenic factors and other molecules
      involved in downstream intracellular signaling pathways, including receptor
      tyrosine kinases. However, therapeutic advances in gastric cancer are not so
      encouraging when compared to other solid organ malignancies such as breast and
      colorectal cancer. This article reviews the role of targeted agents in gastric
      cancer as single-agent therapy or in combination regimens, including their
      rational and emerging mechanism of action, current and emerging data. We focused
      our attention mainly on published phase III studies, therefore cornerstone
      clinical trials with trastuzumab and bevacizumab have been largely discussed.
      Phase III studies presented in important international meetings are also reviewed
      as well phase II published studies and promising new therapies investigated in
      preclinical or phase I studies. Today, in first-line treatment only trastuzumab
      has shown significantly increased survival in combination with chemotherapy,
      whereas ramucirumab as single agent resulted effective in progressing patients,
      but - despite several disappointing results - these are the proof of principle
      that targeting the proper molecular aberration is the best way for implementing
      outcome of therapy. 

PMID- 24304283
TI  - Amyloid aggregation inhibitory mechanism of arginine-rich D-peptides.
AB  - It is widely believed that Alzheimer's disease pathogenesis is driven by the
      production and deposition of the amyloid-beta peptide (Abeta) in the brain. In
      this study, we employ a combination of in silico and in vitro approaches to
      investigate the inhibitory properties of selected arginine-rich D-enantiomeric
      peptides (D-peptides) against amyloid aggregation. The D-peptides include D3, a
      12-residue peptide with anti-amyloid potencies demonstrated in vitro and in vivo,
      RD2, a scrambled sequence of D3, as well as truncated RD2 variants. Using a
      global optimization method together with binding free energy calculations
      followed by molecular dynamics simulations, we perform a detailed analysis of D
      peptide binding to Abeta monomer and a fibrillar Abeta structure. Results
      obtained from both molecular simulations and surface plasmon resonance
      experiments reveal a strong binding of D3 and RD2 to Abeta, leading to a
      significant reduction in the amount of beta structures in both monomer and
      fibril, which was also demonstrated in Thioflavin T assays. The binding of the D
      peptides to Abeta is driven by electrostatic interactions, mostly involving the D
      arginine residues and Glu11, Glu22 and Asp23 of Abeta. Furthermore, we show that
      the anti-amyloid activities of the D-peptides depend on the length and sequence
      of the Dpeptide, its ability to form multiple weak hydrophobic interactions with
      Abeta, as well as the Abeta oligomer size. 

PMID- 24304284
TI  - Adipocytes contribute to resistance of human melanoma cells to chemotherapy and
      targeted therapy.
AB  - Epidemiological evidence has linked the development and progression of several
      cancers including melanoma with obesity. However, whether obesity impinges on
      responses of cancer cells to treatment remains less understood. Here we report
      that human adipocytes contribute to resistance of melanoma cells to various
      therapeutic agents. Exposure to media from adipocyte cultures (adipocyte media)
      increased cell proliferation and reduced sensitivity of melanoma cells to
      apoptosis induced by diverse chemotherapeutic drugs, including the DNA-damaging
      drug cisplatin, the microtubuletargeting agent docetaxel, and the histone
      deacetylase inhibitor SAHA. This was associated with increased activation of
      PI3K/Akt and MEK/ERK signaling, and was attenuated by a PI3K or MEK inhibitor.
      The effect of adipocyte media on melanoma cells was, at least in part, due to the
      interaction between the adipokine leptin and its long form receptor OB-Rb, in
      that immunodepletion of leptin in adipocyte media or siRNA knockdown of OB-Rb in
      melanoma cells reversed the increase in Akt and ERK activation, enhancement in
      cell proliferation, and importantly, protection of melanoma cells against the
      drugs. In support, recombinant leptin partially recapitulated the effect of
      adipocyte media on melanoma cells. Of note, OB-Rb was increased on the surface of
      melanoma cells compared to melanocytes, whereas leptin short form receptors
      appeared to be suppressed post-transcriptionally, suggesting that OB-Rb was
      selectively upregulated in melanoma cells. Collectively, these results indicate
      that adipocytes contribute to the resistance of melanoma cells to
      chemotherapeutic drugs and agents targeting the PI3K/Akt and MEK/ERK pathways,
      and suggest that inhibition of the leptin/ OB-Rb system may be useful to improve
      the efficacy of multiple therapeutic approaches in the treatment of melanoma. 

PMID- 24304286
TI  - Cyclic-3-hydroxymelatonin (C3HOM), a potent antioxidant, scavenges free radicals
      and suppresses oxidative reactions.
AB  - Cyclic 3-hydroxymelatonin (C3HOM) is an immediate product of melatonin's
      interaction with reactive oxygen species. Its presence has been detected in mice,
      rats and humans. In the current study, the antioxidant capacity and reducing
      power of this molecule have been systematically studied. C3HOM is found to be a
      more potent antioxidant than melatonin or vitamin C in terms of its ability to
      scavenge the hydroxyl radical (HO.) and to recover oxidized horseradish
      peroxidase to its ground state. The antioxidative mechanism of C3HOM is similar
      to that of the classic antioxidant, vitamin C, rather than to its precursor
      melatonin. C3HOM effectively prevents the oxidative degradation of cytochrome C
      induced by hydrogen peroxide (H2O2). It is speculated that some antioxidative
      activities of melatonin may be mediated by its metabolite, C3HOM. C3HOM prevents
      mitochondrial cytochrome C injury and, thus, it is likely to inhibit cellular
      apoptosis induced by the release of oxidized cytochrome C from mitochondria.

PMID- 24304285
TI  - HIV-antigens charged on phosphorus dendrimers as tools for tolerogenic dendritic
      cells-based immunotherapy.
AB  - AIMS: The objective was to study if cationic phosphorus dendrimers can be used as
      DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated
      with HIV-1 derived peptides. MATERIALS & METHODS: The HIV derived peptides uptake
      in DC and the phenotype of iDC and mDC were studied using Flow Cytometry
      analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay.
      Allogenic T-cells proliferative response induced by DC was studied using Flow
      Cytometry assays. Cytokines production was analysed by Diaclon DIAplex
      Th1/Th2/Inflammation kit. RESULTS: All phosphorus dendrimers showed the ability
      to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and
      third generations induced important changes in phenotype. Moreover, the treatment
      of mDC with the second generation dendrimer and derivated dendriplexes modified
      cellular migratory properties, altered their capacity to stimulate allogenic
      naive T cells in vitro and impeded the production of pro-inflammatory cytokines.
      CONCLUSIONS: The phosphorus dendrimers cannot be used as vaccines because they
      would not have the ability to induce an immune response. The cationic phosphorus
      dendrimers associated with HIV-derived peptides have the ability to deliver
      peptides as non-viral vectors. However, there are other potential therapeutic
      applications of these compounds, for instance as topical antiinflammatory agents,
      as compounds for allograft rejection or autoimmune diseases and as agents
      inducing specific tolerance with antigen-loaded DC against allergy reaction.
      Nevertheless, these applications need to be evaluated.

PMID- 24304287
TI  - Translation and cultural adaptation of an objective pain assessment tool for
      Finnish ICU patients.
AB  - AIM: The purpose of this study was to culturally validate three pain measurement
      instruments [Behavioral Pain Scale (BPS), the Critical-Care Pain Observation Tool
      (CPOT) and the Nonverbal Adult Pain Assessment Scale (NVPS)] for sedated
      intensive care patients and in doing so to prepare the tools for psychometric
      testing in the Finnish intensive care environment. BACKGROUND: Most patients feel
      pain during their stay in an intensive care unit. Pain recognition and assessment
      is the first step towards effective pain management. The BPS, CPOT and NVPS are
      the most valid and reliable pain assessment instruments developed to objectively
      assess pain in sedated intensive care patients. METHOD: The translation and
      cultural adaptation of the instruments were done according to the guidelines of
      the International Society for Pharmacoeconomics and Outcomes (ISPOR). The process
      included 10 phases aiming to produce semantically correct Finnish versions of the
      pain assessment instruments. This translation process was chosen due to its
      rigorousness and systematic approach. RESULTS: The 10-step translation and
      cultural validation process were successfully conducted, although it was complex
      and time-consuming. The resulting Finnish versions of the three pain assessment
      instruments showed good evidence of content and conceptual equivalence. Although
      further work is needed to test these instruments in the Finnish intensive care
      context, the current Finnish versions are potential instruments for clinicians to
      use. CONCLUSION: Deciding when this high-quality process is needed requires
      thorough consideration. However, it is worthwhile to use it when implementing new
      instruments at a national level. We need a valid, reliable and feasible
      instrument for pain assessment in sedated intensive care patients in Finland. The
      next step in our process is conducting psychometric testing of these three
      instruments to choose the tool with the best properties to be implemented in
      clinical practice.

PMID- 24304288
TI  - Drug survival rates in patients with psoriasis after treatment with biologics.
AB  - Clinically, patients' adherence to biologic treatment is not only related to
      efficacy but also to adverse events, cost and other factors. To evaluate long
      term viability of biologic treatment, both the percentage of and reasons for
      discontinuation of treatment were investigated. In this study, patients treated
      with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were
      included and observed for 12 months. Clinical efficacy was evaluated using a 75%
      reduction of Psoriasis Area and Severity Index score (PASI-75), and patients who
      discontinued treatment were considered as not having achieved PASI-75. In
      addition, drug survival rate (DSR) was investigated. In patients treated with
      infliximab, PASI-75 was 68.4% and DSR was 73.3% by the end of treatment. In
      patients treated with adalimumab, PASI-75 was 50.8% and DSR was 79.7%. In
      patients treated with ustekinumab, PASI-75 was 63.3% and DSR was 96.7%. Several
      patients discontinued treatment because of insufficient efficacy due to secondary
      failure in infliximab or primary failure in adalimumab. To increase treatment
      efficacy, it will be necessary for these patients to use an additional
      concomitant treatment. Higher efficacy is expected with biologics than with
      conventional treatments; however, the actual clinical efficacy over a long period
      of time may be insufficient if they are used without any concomitant treatments. 

PMID- 24304289
TI  - Cardiac amyloidosis cases with relative apical sparing of longitudinal strain.

PMID- 24304290
TI  - Pre-fabricated zirconium dioxide implant abutments for single-tooth replacement
      in the posterior region: success and failure after 3 years of function.
AB  - OBJECTIVE: Zirconia implant abutments have gained a much broader clinical use
      over the past few years. The aim of the present study was to assess the clinical
      performance of a pre-fabricated zirconium dioxide implant abutment for single
      tooth replacement in the posterior region. MATERIALS AND METHODS: Forty implants
      of the XiVE((r)) S plus screw type (DENTSPLY Friadent, Mannheim, Germany) were
      inserted in the posterior region of 24 patients and provided with zirconium
      dioxide abutments (FRIADENT((r)) CERCON((r)) Abutment, DENTSPLY Friadent). The
      following parameters were used to document the state of soft tissue: modified
      plaque index, modified sulcus bleeding index and pocket depth. Mesial and distal
      bone levels were determined on radiographs during the prosthetic treatment and at
      the 36-month recall. RESULTS: Thirty-seven implants could be followed up after 36
      months in function. One patient wearing two abutments was lost to follow-up. One
      abutment exhibited a rotational misfit after 2 years in function. A further
      abutment showed the same failure at the 36-months recall appointment. In the
      remaining 36 implants the soft and hard tissue parameters were indicative of a
      low inflammatory status. Compared to the baseline situation, a partly significant
      bone apposition could be observed. Chipping of parts of the veneering ceramic was
      registered in 22% of the remaining implant restorations. CONCLUSIONS: The use of
      zirconia abutments in this study lead to mainly healthy peri-implant hard and
      soft tissue conditions but, considering the observed failures after 3 years in
      function, clinical long-term results should be awaited before recommending full
      zirconia implant abutments in a posterior indication.

PMID- 24304291
TI  - A randomized controlled trial: the efficacy of eluoride rinse combined with
      calcium pre-rinse to increase overnight salivary fluoride.
AB  - BACKGROUND: Previous studies have shown that a calcium (Ca) pre-rinse given
      before a 228 ppm fluoride (F) rinse greatly increased salivary fluoride.
      Objectives. The aim of this randomized controlled trial is to examine if Ca pre
      rinse could increase the fluoride concentration in the overnight unstimulated
      saliva after a 905 ppm F-rinse. MATERIALS AND METHODS: Pre-rinses containing 150
      mM, 75 mM or 0 mM Ca-lactate prepared by a validated pharmaceutical cGPM
      procedure were tested by nine subjects in a randomized order immediately followed
      by a 905 ppm F-rinse. The fluoride concentration was measured in unstimulated
      saliva collected 10 h later. RESULTS AND CONCLUSIONS: The Ca pre-treatment
      significantly increased F level in overnight saliva following the 905 ppm
      fluoride rinse by 1.7* relative to the 905 ppm F-rinse alone; however, a
      significant effect was only observed with the highest (150 mM) Ca concentration
      as pre-rinse. Clinical relevance. High concentration F rinses (905 ppm) are
      commonly recommended for patients at high-risk of caries. A pre-treatment with
      high levels of Ca may further improve the cariostatic effect of this ion.

PMID- 24304292
TI  - Does the type and frequency of palliative care services received by patients with
      advanced heart failure impact symptom burden?

PMID- 24304293
TI  - Influence of molecular structure on the size, shape, and nanostructure of
      nonionic C(n)E(m) surfactant micelles.
AB  - Nonionic alkyl ethoxylates (C(n)E(m)) have been extensively studied for their
      adsorption, aggregation, and solubilization individually and in small groups. In
      this work, we report a more systematic study of the effects of alkyl chain (tail)
      and ethoxylate (head) length on the size, shape, and extent of intermixing within
      the C(n)E(m) micelles in aqueous solution. Data from small angle neutron
      scattering (SANS) and nuclear magnetic resonance (NMR) were combined to undertake
      the structural characterization of micelles formed from the two separate series
      of surfactants C(n)E6 (n = 10, 12, 14) and C12E(m) (m = 5, 6, 8, 10, 12). The
      micellar core volume (V(core)) could be well determined with reasonable accuracy
      and linked to the hydrophilic-lipophilic balance (HLB) of the surfactant, with a
      sharp size and shape transition occurring around HLB = 12.5. NOESY NMR results
      revealed protrusions of the terminal methylene groups into the ethoxylate shell,
      thus providing direct experimental evidence for the phenomenon of "roughness" or
      intermixing of the core-shell interface. These detailed studies are compared with
      previous investigations on this model surfactant system.

PMID- 24304294
TI  - Abstracts of the Australasian Professional Society on Alcohol and other Drugs
      Conference. November 24-27, 2013. Brisbane, Australia.

PMID- 24304297
TI  - Catalytic C-C bond-forming multi-component cascade or domino reactions: pushing
      the boundaries of complexity in asymmetric organocatalysis.

PMID- 24304295
TI  - Testing a social ecological model of alcohol use: the California 50-city study.
AB  - BACKGROUND AND AIMS: Social ecological theories suggest that greater community
      alcohol availability and individual drinker characteristics should jointly affect
      drinking patterns and the use of drinking contexts. We assessed relationships of
      demographic and personality characteristics of individual drinkers and
      environmental characteristics at the city-level to measures of drinking patterns
      and use of drinking contexts. DESIGN: Multi-level statistical analyses of
      archival and survey data from 50 cities in California, USA. SETTINGS: An
      ecological sample of 50 geographically distinct cities with populations from 50
      000 to 500 000 people. PARTICIPANTS: General population telephone survey of 8553
      adults 18 years of age and older stratified by cities. MEASUREMENTS: Archival
      data on city-level alcohol outlet densities were combined with individual survey
      data identifying community conditions, individual demographic and psychosocial
      characteristics, frequencies of use of drinking contexts and drinking patterns.
      FINDINGS: Greater on-premise outlet densities were related to greater drinking
      frequencies (b = 2.9671, z = 4.688, P < 0.001) and volumes (b = 0.6274, z =
      3.394, P < 0.001) and use of on-premises drinking places (bars, b = 0.3340, z =
      2.645, P < 0.006 and restaurants, b = 0.1712, z = 2.770, P = 0.005). Individual
      demographic and personality characteristics were related to drinking and use of
      drinking contexts. For example, greater impulsivity was related to greater
      drinking frequencies (b = 0.2001, z = 2.088, P = 0.023) and logged quantities (b
      = 0.0151, z = 2.009, P = 0.026) and proportionately more drinking at bars (b =
      0.0332, z = 2.016, P = 0.026) and parties (b = 0.1712, z = 2.770, P = 0.004).
      CONCLUSION: Community availability of alcohol and individual drinker
      characteristics appear to act jointly to affect drinking levels and use of
      drinking contexts. These effects may increase risks related to drinking in some
      contexts (e.g. bars) much more than others (e.g. at friends' or relatives'
      homes).

PMID- 24304298
TI  - A new cyclic tetrapeptide from an endophytic Streptomyces sp. YIM67005.
AB  - One new cyclic tetrapeptide, cyclo(L-Tyr-L-Pro-L-Phe-trans-4-hydroxy-L-Pro) (1),
      together with two known cyclodipeptides, cyclo(L-Phe-trans-4-hydroxy-L-Pro) (2)
      and cyclo(L-Val-L-Tyr) (3), were isolated from the fermentation broth of
      Streptomyces sp. YIM67005 associated with Inula cappa DC. The planar structure of
      compound 1 was determined on the basis of spectroscopic techniques, while the
      absolute configurations of the amino acid residues were determined by the
      application of the advanced Marfey method. The cytotoxicity and antimicrobial
      activity of compound 1 were investigated.

PMID- 24304299
TI  - Model peptides uncover the role of the beta-secretase transmembrane sequence in
      metal ion mediated oligomerization.
AB  - The beta-secretase or beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1) is the enzyme responsible for the formation of amyloid-beta peptides,
      which have a major role in Alzheimer pathogenesis. BACE1 has a transmembrane
      sequence (TMS), which makes it unique among related proteases. We noticed that
      the BACE1 TMS contains an uncommon sulfur-rich motif. The sequence
      MxxxCxxxMxxxCxMxC spans the entire TMS, resembles metal ion binding motifs, and
      is highly conserved among homologues. We used a synthetic 31-mer model peptide
      comprising the TMS to study metal ion binding and oligomerization. Applying
      diverse biochemical and biophysical techniques, we detected dimer and trimer
      formation of the TMS peptide with copper ions. Replacement of the central Cys466
      by Ala essentially abolished these effects. We show that the peptide undergoes a
      redox reaction with copper ions resulting in a disulfide bridge involving Cys466.
      Further, we find peptide trimerization that depends on the presence of monovalent
      copper ions and the sulfhydryl group of Cys466. We identified Cys466 as a key
      residue for metal ion chelation and to be the core of an oligomerization motif of
      the BACE1-TMS peptide. Our results demonstrate a novel metal ion controlled
      oligomerization of the BACE1 TMS, which could have an enormous therapeutic
      importance against Alzheimer disease. 

PMID- 24304300
TI  - Authors' reply to Drs M van Blitterswijk, R Rademakers and LH van den Berg.

PMID- 24304301
TI  - Atropisomerization in N-aryl-2(1H)-pyrimidin-(thi)ones: a ring
      opening/rotation/ring-closure process in place of a classical rotation around the
      pivot bond.
AB  - Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are
      classically described as the result of the rotation around the pivotal single
      bond linking two planar frameworks. Severe constraints leading to more or less
      distorted transition states account for the experimental barrier to
      atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)
      pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the
      observed racemization process accounting for the lower barriers in the sulfur
      analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano
      1,4-disubstituted-2(1H)-pyrimidinones 5a-5f and two 6-amino-5-cyano-4-p-tolyl-1
      substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized
      through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral
      separation was achieved, and enantiomerization barriers were obtained by thermal
      racemization. The rotational barriers of 6-amino-5-cyano-1-o-tolyl-4-p-tolyl
      2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)
      pyrimidinone (5e) were found to be 120.4 and 125.1 kJ.mol(-1) (n-BuOH, 117 
      degrees C), respectively, and those of the corresponding thiones were 116.8 and
      109.6 kJ.mol(-1) (EtOH, 78  degrees C), respectively. DFT calculations of the
      rotational barriers clearly ruled out the classical rotation around the pivotal
      bond with distorted transition states in the case of the sulfur derivatives.
      Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o
      tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations
      when the rotation occurred via a ring-opened form in N-aryl-2(1H)
      pyrimidinethiones. 

PMID- 24304302
TI  - Detection and characterization of nanomaterials released in low concentrations
      during multi-walled carbon nanotube spraying process in a cleanroom.
AB  - Release of nanomaterials was assessed in a cleanroom workplace designed for the
      handling of multi-walled carbon nanotubes. During the process, the nanotubes were
      sprayed in a chamber fitted with an exhaust duct system. The front door of the
      spraying chamber was completely closed, but rear end of the chamber was partially
      open. Throughout a series of spray processes, three detectors - an optical
      particle counter, a nanoparticle aerosol monitor, and an aethalometer - counted
      and characterized particles escaping the chamber. Concentrations of particle
      surface area and black carbon emitted by the spraying were assessed assuming zero
      background aerosol concentration in the cleanroom. Very low concentrations of
      black carbon, 0.4 MUg/m(3), were observed. In conclusion, in a cleanroom, low
      concentrations of nanomaterials were detected to be emitted from a spraying
      chamber into the workplace. The level of particles reaching the workplace was
      sufficiently low to have made their detection difficult in a normal environment.
      Both target nanomaterial and non-intended incidental nanomaterials were released
      during spraying. Despite the use of exhaust duct system in the process chamber,
      workers would be exposed to some particles if the chamber were partially open.
      The exhaust duct system was not enough to remove all the particles released in
      the chamber.

PMID- 24304303
TI  - Comparison of how ambient PMc and PM2.5 influence the inflammatory potential.
AB  - Airborne particulate matter (PM) is one of the six criteria air pollutants
      currently regulated by the U.S. Environmental Protection Agency (EPA), with
      existing ambient standards for PM2.5 and PM10. Currently there are no health
      based regulations for the size fraction between 2.5 and 10 um, commonly known as
      the coarse fraction (PMc). The present study investigates current gaps in
      knowledge for PMc including exposure toxicity and PM ratios (PMc:PM2.5) in PM10.
      Throughout the world, all the three PM size fractions have been shown to be
      associated with adverse impacts. Recent studies have shown that PMc can be more
      detrimental to susceptible populations when directly compared to PM2.5, and that
      the PMc fraction in PM10 can account for the majority of the inflammatory
      response from PM10 exposure. In our studies we utilized a bone marrow-derived
      mouse macrophage in vitro system to compare the inflammatory potential of PMc,
      PM2.5 and mixtures of the two. The result was a linear increase in
      interleukin(IL) -1beta with increasing levels of exposure to winter and summer
      PMc, as compared to PM2.5, which exhibited logarithmic growth. Also, exposure to
      PM10 as a function of PM2.5 and PMc mass ratios showed that IL-1beta and TNF
      alpha levels increased synergistically with a greater burden of PMc. Endotoxin
      content in the PM did not correlate with these results, suggesting that other
      activators in PMc are likely responsible for activating the NF-kappaB pathway and
      the inflammasome.

PMID- 24304305
TI  - Estimating safe human exposure levels for lunar dust using benchmark dose
      modeling of data from inhalation studies in rats.
AB  - The pulmonary toxicity of airborne lunar dust was assessed in rats exposed by
      nose-only inhalation to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable size lunar
      dust. Rats were exposed for 6 h/d, 5 d/week, for 4 weeks (120 h). Biomarkers of
      toxicity were assessed in bronchial alveolar lavage fluid (BALF) collected at 1
      d, 1 week, 4 weeks or 13 weeks post-exposure for a total of 76 endpoints.
      Benchmark dose (BMD) analysis was conducted on endpoints that appeared to be
      sensitive to dose. The number of endpoints that met criteria for modeling was 30.
      This number was composed of 13 endpoints that produced data suitable for
      parametric analysis and 17 that produced non-normal data. Mean BMD values
      determined from models generated from non-normal data were lower but not
      significantly different from the mean BMD of models derived from normally
      distributed data. Thus BMDs ranged from a minimum of 10.4 (using the average BMD
      from all 30 modeled endpoints) to a maximum of 16.6 (using the average BMD from
      the most restricted set of models). This range of BMDs yields safe exposure
      estimate (SEE) values of 0.6 and 0.9 mg/m3, respectively, when BMDs are
      extrapolated to humans, using a species factor of 3 and extrapolated from a 1
      month exposure to an anticipated 6-month lunar surface exposure. This estimate is
      very similar to a no-observable-adverse-effect-level (NOAEL) determined from the
      same studies (0.4 mg/m3) and a SEE derived from a study of rats that were
      intratracheally instilled with lunar dusts (0.5-1.0 mg/m3).

PMID- 24304304
TI  - Asbestos-associated mesothelial cell autoantibodies promote collagen deposition
      in vitro.
AB  - Fibrosis, characterized by excessive collagen protein deposition, is a
      progressive disease that can fatally inhibit organ function. Prolonged exposure
      to pathogens or environmental toxicants such as asbestos can lead to chronic
      inflammatory responses associated with fibrosis. Significant exposure to
      amphibole asbestos has been reported in and around Libby, Montana due to local
      mining of asbestos-contaminated vermiculite. These exposures have been implicated
      in a unique disease etiology characterized predominantly by pleural disorders,
      including fibrosis. We recently reported the discovery of mesothelial cell
      autoantibodies (MCAAs) in the sera of Libby residents and demonstrated a positive
      and significant correlation with pleural disease; however, a mechanistic link was
      not determined. Here we demonstrate that MCAAs induce pleural mesothelial cells
      to produce a collagen matrix but do not affect production of the pro-inflammatory
      cytokine tumor growth factor-beta. While autoantibodies commonly induce a pro
      fibrotic state by inducing epithelial-mesenchymal transition (EMT) of target
      cells, we found no evidence supporting EMT in cells exposed to MCAA positive
      human sera. Although implicated in other models of pulmonary fibrosis, activity
      of the protein SPARC (secreted protein, acidic and rich in cysteine) did not
      affect MCAA-induced collagen deposition. However, matrix formation was dependent
      on matrix metalloproteinase (MMP) activity, and we noted increased expression of
      MMP-8 and -9 in supernatants of mesothelial cells incubated with MCAA positive
      sera compared to control. These data suggest a mechanism by which MCAA binding
      leads to increased collagen deposition through altering MMP expression and
      provides an important mechanistic link between MCAAs and asbestos-related,
      autoimmune-induced pleural fibrosis.

PMID- 24304306
TI  - Home cage locomotor changes in non-human primates after prolonged welding-fume
      exposure.
AB  - To define the relationship between the brain concentration of manganese and
      neurological signs, such as locomotion, after prolonged welding-fume exposure,
      cynomolgus monkeys were acclimated for 1 month and then divided into three
      concentration groups: unexposed, low concentration (31 mg/m(3) total suspended
      particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP,
      1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc
      stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an
      inhalation chamber system equipped with an automatic fume generator. The home
      cage locomotor activity and patterns were determined using a camera system over 2
      4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor
      activity of the high-concentration primates was found to be 5-6 times higher than
      that of the unexposed primates, and this increased locomotor activity was
      maintained for 7 weeks after ceasing the welding-fume exposure, eventually
      subsiding to three times higher after 13 weeks of recovery. Therefore, the
      present results, along with our previous observations of a high magnetic
      resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn
      concentration, indicate that prolonged welding-fume exposure can cause
      neurobehavioral changes in cynomolgus monkeys.

PMID- 24304308
TI  - Estimating lung burdens based on individual particle density estimated from
      scanning electron microscopy and cascade impactor samples.
AB  - Workplace air is monitored for overall dust levels and for specific components of
      the dust to determine compliance with occupational and workplace standards
      established by regulatory bodies for worker health protection. Exposure
      monitoring studies were conducted by the International Copper Association (ICA)
      at various industrial facilities around the world working with copper. Individual
      cascade impactor stages were weighed to determine the total amount of dust
      collected on the stage, and then the amounts of soluble and insoluble copper and
      other metals on each stage were determined; speciation was not determined. Filter
      samples were also collected for scanning electron microscope analysis.
      Retrospectively, there was an interest in obtaining estimates of alveolar lung
      burdens of copper in workers engaged in tasks requiring different levels of
      exertion as reflected by their minute ventilation. However, mechanistic lung
      dosimetry models estimate alveolar lung burdens based on particle Stoke's
      diameter. In order to use these dosimetry models the mass-based, aerodynamic
      diameter distribution (which was measured) had to be transformed into a
      distribution of Stoke's diameters, requiring an estimation be made of individual
      particle density. This density value was estimated by using cascade impactor data
      together with scanning electron microscopy data from filter samples. The
      developed method was applied to ICA monitoring data sets and then the multiple
      path particle dosimetry (MPPD) model was used to determine the copper alveolar
      lung burdens for workers with different functional residual capacities engaged in
      activities requiring a range of minute ventilation levels.

PMID- 24304309
TI  - Increased osmolarity and cell clustering preserve canine notochordal cell
      phenotype in culture.
AB  - Degeneration of the intervertebral disc (IVD) is associated with a loss of
      notochordal cells (NCs) from the nucleus pulposus (NP) and their replacement by
      chondrocyte-like cells. NCs are known to maintain extracellular matrix quality
      and stimulate the chondrocyte-like NP cells, making NCs attractive for designing
      new tissue engineering approaches for IVD regeneration. However, optimal
      conditions, such as osmolarity and other characteristics of the culture media,
      for long-term culture of NCs are not known. The purpose of this study was to
      investigate the effects of different culture media and osmolarity on the
      physiology of NCs in vitro. NC clusters isolated from canine IVDs were suspended
      in alginate beads and cultured at 37 degrees C under normoxic conditions for 28
      days. Three different culture conditions were investigated; (1) Dulbecco's
      modified Eagle's medium (DMEM)/F12 (300 mOsm/L), (2) alpha-MEM (300 mOsm/L), and
      (3) alpha-MEM adjusted to 400 mOsm/L to mimic a hyperosmolar environment. NC
      morphology, expression of genes related to NC markers, matrix production and
      remodeling, and DNA- and glycosaminoglycan (GAG) analyses were performed on 1, 7,
      14, and 28 days in culture. Large, vesicle-containing cells organized in
      clusters, characterized as NCs, remained present during 28 days for all culture
      conditions. However, the proportion of the NC clusters decreased over time,
      whereas the proportion of spindle-shaped cells increased. Gene expression
      profiling at 7, 14, and 28 days in culture compared to day 1 indicated a initial
      loss of NC phenotype followed by some recovery of brachyury and aggrecan gene
      expression after 28 days of culture supporting a potential recovery of NC
      phenotype. NCs cultured in alpha-MEM adjusted to 400 mOsm/L showed the highest
      gene expression of brachyury, cytokeratin 18, and aggrecan, the highest GAG
      production, and the lowest collagen 1alpha1 gene expression. In conclusion, NCs
      cultured in alginate in native cell clusters, partially retained their
      characteristic morphology and recovered their phenotype in long-term culture. The
      type of culture medium and medium osmolarity appear to be important factors for
      culturing NC clusters. These findings provide additional information concerning
      the maintenance of NCs in vitro that may aid further mechanistic inquiry into the
      biology of NCs.

PMID- 24304307
TI  - Particulate matter beyond mass: recent health evidence on the role of fractions,
      chemical constituents and sources of emission.
AB  - Particulate matter (PM) is regulated in various parts of the world based on
      specific size cut offs, often expressed as 10 or 2.5 um mass median aerodynamic
      diameter. This pollutant is deemed one of the most dangerous to health and
      moreover, problems persist with high ambient concentrations. Continuing pressure
      to re-evaluate ambient air quality standards stems from research that not only
      has identified effects at low levels of PM but which also has revealed that
      reductions in certain components, sources and size fractions may best protect
      public health. Considerable amount of published information have emerged from
      toxicological research in recent years. Accumulating evidence has identified
      additional air quality metrics (e.g. black carbon, secondary organic and
      inorganic aerosols) that may be valuable in evaluating the health risks of, for
      example, primary combustion particles from traffic emissions, which are not fully
      taken into account with PM2.5 mass. Most of the evidence accumulated so far is
      for an adverse effect on health of carbonaceous material from traffic. Traffic
      generated dust, including road, brake and tire wear, also contribute to the
      adverse effects on health. Exposure durations from a few minutes up to a year
      have been linked with adverse effects. The new evidence collected supports the
      scientific conclusions of the World Health Organization Air Quality Guidelines
      and also provides scientific arguments for taking decisive actions to improve air
      quality and reduce the global burden of disease associated with air pollution.

PMID- 24304310
TI  - A practical guide to sequencing genomes and transcriptomes.
AB  - The emergence of new DNA sequencing technologies has allowed an exponential
      growth of genomic and transcriptomic data that ultimately yielded important
      results to several areas such as medicine and biology. This continuous
      technological progress presents several advantages and caveats that have to be
      considered for each new method. In this review, we describe the so-called second
      and third generation DNA sequencing technologies, how they changed the study of
      genomes and transcriptomes, and most importantly, what are the key factors that
      should be considered in a sequencing project. Taken together, we present a
      "sequencing project map" that includes a practical and graphical cost-benefit
      analysis for genome and transcriptome projects which allows scientist to easily
      classify their workflow into one of our proposed templates according to the goals
      and experimental design of the project at hand. In all, this review reflects the
      pros and cons of the most widely adopted experimental designs, sequencing
      technologies, and exposes them to help scientists interested in these tools to
      choose the best strategy for their project. 

PMID- 24304311
TI  - Characterization of protein complexes using targeted proteomics.
AB  - Biological systems are not only controlled by the abundance of individual
      proteins, but also by the formation of complexes and the dynamics of protein
      protein interactions. The identification of the components of protein complexes
      can be obtained by shotgun proteomics using affinity purification coupled to mass
      spectrometry. Such studies include the analyses of several samples and
      experimental controls in order to discriminate true specific interactions from
      unspecific interactions and contaminants. However, shotgun proteomics have
      limited quantification capabilities for low abundant proteins on large sample
      sets due to the undersampling and the stochastic precursor ion selection. In this
      context, targeted proteomics constitutes a powerful analytical tool to
      systematically detect and quantify peptides in multiple samples, for instance
      those obtained from affinity purification experiments. Hypothesis-driven
      strategies have mainly relied on the selected reaction monitoring (SRM) technique
      performed on triple quadrupole instruments, which enables highly selective and
      sensitive measurements of peptides, acting as surrogates of the pre-selected
      proteins, over a wide range of concentrations. More recently, novel quantitative
      methods based on high resolution instruments, such as the parallel reaction
      monitoring (PRM) technique implemented on the quadrupole-orbitrap instrument,
      have arisen and provided alternatives to perform quantitative analyses with
      enhanced selectivity.The application of targeted proteomics to protein-protein
      interaction experiments from plasma and other physiological fluid samples and the
      inclusion of parallel reaction monitoring (PRM), combined with other recent
      technology developments opens a vast area for clinical application of proteomics.
      It is anticipated that it will reveal valuable information about specific,
      individual, responses against drugs, exogenous proteins or pathogens. 

PMID- 24304312
TI  - Regulation by IFN-alpha/IFN-gamma co-formulation (HerberPAG(r)) of genes involved
      in interferon-STAT-pathways and apoptosis in U87MG.
AB  - Interferons (IFNs) are proteins of the family of cytokines. Their
      antiproliferative function has been taken into account for several clinical
      therapies against malignant diseases. In this family, IFNs alpha and gamma have
      demonstrated the highest antitumor effects. HerberPAG(r) is a new co-formulation
      with IFNs, alpha2b and gamma. It has been obtained to increase the
      antiproliferative effect of individual IFNs and decrease their associated
      toxicity. Glioblastoma multiforme (GBM) is the most common primary brain tumor
      and one of the most deadly forms of cancer. The objective of the present work is
      to obtain insights into the regulation of Interferon-STAT-pathways and apoptosis
      in U87MG, at the transcriptional level. As a pharmacogenomic strategy we
      quantified mRNAs levels in vitro by quantitative PCR, using the cell line U87MG
      as a model. Some of the genes involved in the first steps of IFNs signaling
      pathways (stat1 and stat3) and apoptosis events (tp53, bax, bcl-2, bad, caspase3
      (casp3), caspase8 (casp8) and caspase9 (casp9)) were studied. The detected mRNAs
      expression pattern for stat1and stat3 indicates a higher tumor suppressor
      activity of HerberPAG(r) compared to individuals IFNs. The up-regulation of tp53,
      bax, bad, casp3, casp8 and casp9 genes and the down regulation of bcl-2 gen,
      after the treatment with HerberPAG(r) show a pro-apoptotic function. HerberPAG(r)
      gene-induced profile shows an advantage in relation to IFN alpha2b and gamma with
      a higher stat1 expression and a downregulation of bcl-2 which increases bax:bcl-2
      ratio. The regulation of genes involved in IFN-STAT-pathways and apoptosis may be
      the first evidences to explain the increased antiproliferative properties of this
      co-formulation.

PMID- 24304313
TI  - Potential correlation between tumor aggressiveness and protein expression
      patterns of nipple aspirate fluid (NAF) revealed by gel-based proteomic analysis.
AB  - Breast cancer is the leading cause of cancer related deaths in women. Most breast
      cancers stem from mammary ductal cells that secrete nipple aspirate fluid (NAF),
      a biological sample that contains proteins associated with the tumor
      microenvironment. In this study, NAF samples from both breasts of 7 Brazilian
      patients with unilateral breast cancer were analyzed. These samples were
      systematically compared using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) and two-dimensional fluorescence difference gel
      electrophoresis (2D-DIGE); substantial qualitative individual differences were
      observed. In general, when NAF samples were compared from both breasts within the
      same patient their electrophoretic patterns were very similar, regardless of
      their cancer status. A comparison of all patients identified 2 main NAF protein
      profiles. The HomEP, homogeneous expression profile, was characterized by typical
      SDS-PAGE and 2D-DIGE protein patterns that were observed in patients with a good
      breast cancer prognosis and were similar to previous Type I NAF classifications
      that used one-dimensional electrophoresis. The HetEP, heterogeneous expression
      profile, was characterized by distinct protein patterns that have not been
      reported in previous studies and have been primarily observed in breast cancer
      patients with a poor prognosis. The NAF samples were rich in metal-dependent
      proteolytic enzymes, as visualized by SDS-PAGE zymography. They varied
      qualitatively with respect to their gelatinolytic band distribution. However,
      there were no correlations between these characteristics and the pathologic
      features of these tumors. A comparative analysis of NAF samples taken from each
      breast in a single patient showed conserved zymographic patterns. In conclusion,
      the present study highlights important distinctions in the protein content of
      individual NAF samples and provides insight into the composition of the tumor
      microenvironment. These data reinforce breast cancer as a heterogeneous disease
      with a diverse natural history, which is becoming increasingly evident through
      other recent studies. 

PMID- 24304314
TI  - Using mass spectrometry-based peptidomics to understand the brain and disorders
      such as Parkinson's disease and schizophrenia.
AB  - The numerous efforts invested in the identification of biomarkers for
      neurodegenerative and neuropsychiatric disorders, such as Parkinson's disease and
      schizophrenia, are justified because these disorders affect several million
      people worldwide. Although genetic implications and the role of the environment
      have been shown in the progression of those disorders, together with anatomical
      and neurochemical characteristics, an integrated view of the biochemical pathways
      involved in the pathophysiology of these disorders is still being unraveled. The
      use of proteomic methodologies, molecular mechanisms and potential biomarker
      candidates for the prognosis, diagnosis and treatment of brain disorders has been
      discussed. Similar methodologies can be applied for the large-scale
      identification of peptides to characterize the brain peptidome with the aim of
      closing the knowledge gaps that remain. Brain cells contain a large number of
      peptides that play pivotal roles in cell communication. Peptidome studies have
      recently identified more than 800 peptides in mouse brain extracts, with half of
      them derived from secretory pathways. For example, several of these peptides were
      identified as bioactive neuropeptides that activate G-coupled receptors. In
      addition, intracellular peptides derived from nuclear, cytosolic and
      mitochondrial proteins have been identified, including the hemopressins, which
      act with high selectivity for the cannabinoid receptor type 1. Considering the
      importance of peptides in cell signaling, the present review intends to discuss
      the recent findings of the peptidome field, focusing on Parkinson's disease and
      schizophrenia. New approaches to evaluate intracellular peptide signaling at the
      protein-protein interaction level and the future perspectives of peptides as
      intracellular modulators of signal transduction are explored. 

PMID- 24304315
TI  - Alterations of the kidney cortex proteome in response to exercise training in
      normoglycemic and hyperglycemic conditions.
AB  - Hyperglycemia induces systemic vascular endothelial dysfunction and renal damage
      through the overproduction of reactive oxygen species (ROS). Regular aerobic
      exercise decreases the incidence of ROS-associated diseases and is involved in
      protection against systemic and renal vascular alterations. To investigate the
      impact of exercise training on renal protein expression in hyperglycemic
      conditions, we performed gel-based proteomic analyses of the rabbit kidney cortex
      from sedentary and exercised rabbits after exposure to normal or high glucose
      concentrations. Abundance of proteins in the renal cortex was determined by two
      dimensional polyacrylamide gel electrophoresis followed by protein identification
      with mass spectrometry, using peptide mass and fragment fingerprintings. We
      identified the differential abundance of twenty seven proteins in exercise
      trained animals among the total of 324 spots, from which five proteins are
      related to the down-regulation of cellular oxidative stress (albumin, protein
      disulfide isomerase, heat shock protein 60-like chaperonin, DJ-1 and ubiquinol
      cytochrome-c reductase), and three proteins are involved in energy metabolism
      (shortchain acyl-coenzyme A dehydrogenase, malate dehydrogenase and L-arginine
      glycine amidinotransferase). We concluded that exercise training induces an
      increase in the abundance of five antioxidant proteins in the renal cortex, which
      could explain the well-known increase in endothelial-dependent vasodilation that
      results from exercise and the consequential protective effect against increased
      oxidative stress of the hyperglycemic milieu. Moreover, this protective effect
      could be important in the prevention of kidney vascular damage associated with
      diabetes pathophysiology. 

PMID- 24304316
TI  - Proteome analysis of formalin-fixed paraffin-embedded tissues from a primary
      gastric melanoma and its meningeal metastasis: a case report.
AB  - Melanoma is the third most common brain metastasis cause in the United States as
      it has a relatively high susceptibility to metastasize to the central nervous
      system. Among the different origins for brain metastasis, those originating from
      primary gastric melanomas are extremely rare. Here, we compare protein profiles
      obtained from formalin-fixed paraffin- embedded (FFPE) tissues of a primary
      gastric melanoma with its meningeal metastasis. For this, the contents of a
      microscope slide were scraped and ultimately analyzed by nano-chromatography
      coupled online with tandem mass spectrometry using an Orbitrap XL. Our results
      disclose 184 proteins uniquely identified in the primary gastric melanoma, 304 in
      the meningeal metastasis, and 177 in common. Notably, we identified several
      enzymes related to changes in the metabolism that are linked to producing energy
      by elevated rates of glycolysis in a process called the Warburg effect. Moreover,
      we show that our FFPE proteomic approach allowed identification of key biological
      markers such as the S100 protein that we further validated by
      immunohistochemistry for both, the primary and metastatic tumor samples. That
      said, we demonstrated a powerful strategy to retrospectively mine data for aiding
      in the understanding of metastasis, biomarker discovery, and ultimately,
      diseases. To our knowledge, these results disclose for the first time a
      comparison of the proteomic profiles of gastric melanoma and its corresponding
      meningeal metastasis.

PMID- 24304317
TI  - A survey of molecular descriptors used in mass spectrometry based proteomics.
AB  - The field of proteomics has grown vertiginously in the last years. This has been
      due fundamentally to technological improvements in the instrumentation, methods,
      and easy-to-use software, thereby making it possible to address a large number of
      biological questions and to deepen the study of the proteome of several
      organisms. The development in the field has imposed a challenge in the
      computational analysis of the commonly obtained large datasets generated in a
      single proteomics experiment, which still remains. An alternative to tackle this
      general issue has been the use of auxiliary information generated during the
      proteomics experiment to validate the confidence of the identifications. In this
      manuscript we review the main molecular descriptors used for building predictor
      models for estimating retention time, isoelectric point and peptide
      "detectability", which are key tools in the design of several validation
      strategies based in these criteria. We also give an overview of the main open
      source tools and libraries used for computing molecular descriptors. 

PMID- 24304318
TI  - GARM: genome assembly, reconciliation and merging pipeline.
AB  - Over the past decades DNA sequencing technologies have been improving in aspects
      like quality, read length, runtimes and yields, all at a lower cost. Despite
      these improvements, genome assembly remains a challenge in genome sequencing
      projects, especially when different sequencing platforms are used. At the
      present, there is no program that can handle and assemble different sequencing
      technologies better than specialized software for each of them. Also, very few
      protocols are available for merging results from different algorithms,
      technologies or both. We present GARM, (Genome Assembler, Reconciliation and
      Merging) a pipeline to merge assemblies from different algorithms or sequencing
      technologies. 

PMID- 24304319
TI  - Evolutionary analysis of DNA-protein-coding regions based on a genetic code cube
      metric.
AB  - The right estimation of the evolutionary distance between DNA or protein
      sequences is the cornerstone of the current phylogenetic analysis based on
      distance methods. Herein, it is demonstrated that the Manhattan distance (dw),
      weighted by the evolutionary importance of the nucleotide bases in the codon, is
      a naturally derived metric in the standard genetic code cube inserted into the
      three-dimensional Euclidean space. Based on the application of distance dw, a
      novel evolutionary model is proposed. This model includes insertion/deletion
      mutations that are very important for cancer studies, but usually discarded in
      classical evolutionary models. In this study, the new evolutionary model was
      applied to the phylogenetic analysis of the DNA protein-coding regions of 13
      mammal mitochondrial genomes and of four cancer genetic- susceptibility genes
      (ATM, BRCA1, BRCA2 and p53) from nine mammals. The opossum (a marsupial) was used
      as an out-group species for both sets of sequences. The new evolutionary model
      yielded the correct topology, while the current models failed to separate the
      evolutionarily distant species of mouse and opossum. 

PMID- 24304320
TI  - Database construction and peptide identification strategies for proteogenomic
      studies on sequenced genomes.
AB  - Since the advent of high-throughput DNA sequencing technologies, the ever
      increasing rate at which genomes have been published has generated new challenges
      notably at the level of genome annotation. Even if gene predictors and annotation
      softwares are more and more efficient, the ultimate validation is still in the
      observation of predicted gene product( s). Mass-spectrometry based proteomics
      provides the necessary high throughput technology to show evidences of protein
      presence and, from the identified sequences, confirmation or invalidation of
      predicted annotations. We review here different strategies used to perform a MS
      based proteogenomics experiment with a bottom-up approach. We start from the
      strengths and weaknesses of the different database construction strategies, based
      on different genomic information (whole genome, ORF, cDNA, EST or RNA-Seq data),
      which are then used for matching mass spectra to peptides and proteins. We also
      review the important points to be considered for a correct statistical assessment
      of the peptide identifications. Finally, we provide references for tools used to
      map and visualize the peptide identifications back to the original genomic
      information. 

PMID- 24304321
TI  - Bioinformatics tools for the functional interpretation of quantitative proteomics
      results.
AB  - Proteins are the principal mediators of the functions in the cell; therefore, any
      abnormal variations on their abundance levels may reflect the presence of
      pathological processes. In this sense, many researchers rely on the functional
      interpretation of protein lists generated by quantitative proteomics experiments
      to analyze, for instance, these variations in the context of diseases' molecular
      basis and drug discovery. Since no analytical strategy or bioinformatics tool by
      itself is capable of extract all the information covered by a single experiment;
      herein we seek to provide the biologists with four groups of different but
      complementary bioinformatics tools for the functional interpretation of
      quantitative proteomics results. To this end we will review the basic concepts of
      a set of different bioinformatics approaches and we will give examples of freely
      available tools for each one of these approaches.

PMID- 24304322
TI  - Editorial: Genomics and proteomics behind drug design.

PMID- 24304323
TI  - Targeting low-druggability bromodomains: fragment based screening and inhibitor
      design against the BAZ2B bromodomain.
AB  - Bromodomains are epigenetic reader domains that have recently become popular
      targets. In contrast to BET bromodomains, which have proven druggable,
      bromodomains from other regions of the phylogenetic tree have shallower pockets.
      We describe successful targeting of the challenging BAZ2B bromodomain using
      biophysical fragment screening and structure-based optimization of high ligand
      efficiency fragments into a novel series of low-micromolar inhibitors. Our
      results provide attractive leads for development of BAZ2B chemical probes and
      indicate the whole family may be tractable. 

PMID- 24304324
TI  - Neuroimmune interactions at different intestinal sites are related to abdominal
      pain symptoms in children with IBS.
AB  - BACKGROUND: Neuroimmune interactions and inflammation have been proposed as
      factors involved in sensory-motor dysfunction and symptom generation in adult
      irritable bowel syndrome (IBS) patients. In children with IBS and healthy
      controls, we measured ileocolonic mast cell infiltration and fecal calprotectin
      and evaluated the relationships between these parameters and abdominal pain
      symptoms and stooling pattern. METHODS: Irritable bowel syndrome patients
      diagnosed according to Pediatric Rome III criteria and healthy controls kept a 2
      week pain/stooling diary. Ileocolonic mucosal mast cells (MC) and MC in close
      proximity to nerve fibers (MC-NF) were identified immunohistochemically and
      quantified. Fecal calprotectin concentration was measured. KEY RESULTS: 21 IBS
      patients and 10 controls were enrolled. The MC-NF count was significantly higher
      in the ileum (p = 0.01), right colon (p = 0.04), and left colon (p < 0.001) of
      IBS patients compared with controls. No differences in fecal calprotectin
      concentration were noted. Abdominal pain intensity score correlated with ileal MC
      count (r(s) = 0.47, p = 0.030) and right colon MC-NF count (r(s) = 0.52, p =
      0.015). In addition, children with IBS with >3 abdominal pain episodes/week had
      greater ileal (p = 0.002) and right colonic (p = 0.01) MC counts and greater
      ileal (p = 0.05) and right colonic (p = 0.016) MC-NF counts than children with
      less frequent pain. No relationship was found between MC and MC-NF and fecal
      calprotectin or stooling pattern. CONCLUSIONS & INFERENCES: Mast cells-nerve
      fibers counts are increased in the ileocolonic mucosa of children with IBS. Mast
      cells and MC-NF counts are related to the intensity and frequency of abdominal
      pain.

PMID- 24304325
TI  - Prevalence and spectrum of conditions associated with severe tricuspid
      regurgitation.
AB  - BACKGROUND: Data regarding the prevalence and spectrum of conditions associated
      with severe tricuspid regurgitation (TR) are limited to small cohorts. METHODS:
      We retrospectively identified all patients with severe native tricuspid valve
      regurgitation in a large echocardiogram database between January 2004 and
      December 2010. Patients were classified into 1 of 3 groups based on the
      echocardiogram results: (1) organic TR; (2) functional TR; and (3) idiopathic TR.
      RESULTS: Severe TR was identified in 768 (1.2%, 72 +/- 16 years, 64.3% females)
      of 63, 472 consecutive patients referred for transthoracic echocardiography. The
      conditions associated with severe TR could be established in 91% of patients. The
      remaining 9% were classified as idiopathic severe TR with these patients being
      older (78 +/- 10 years) and having a higher frequency of atrial fibrillation
      (63.8%) compared to patients with organic (65 +/- 22 years; 31%) or functional
      severe TR (73 +/- 16 years; 47.8%). Overall, organic severe TR was identified in
      11.3% of all cases. Functional severe TR occurred in 79.7% of the overall cohort
      and was related to pulmonary hypertension and/or left-sided heart disease.
      CONCLUSION: Severe TR occurred with a prevalence of 1.2% in our patients referred
      for echocardiography and was more common in females. Functional severe TR was the
      most common etiology with only a minority of cases secondary to organic severe
      TR. Idiopathic severe TR was found in a small proportion of patients who were
      older and more likely to have atrial fibrillation.

PMID- 24304327
TI  - Endometrial receptivity markers in infertile women stimulated with letrozole
      compared with clomiphene citrate and natural cycles.
AB  - Though various advantages associated with the use of letrozole as an ovulation
      inducing drug are documented, there is inadequate information regarding its
      effect on endometrial receptivity. Expression of endometrial receptivity markers
      including alphavbeta3 integrin, L-selectin, LIF, and pinopods during the
      implantation window in infertile women stimulated with letrozole or clomiphene
      citrate (CC), and spontaneous cycles is investigated. A total of 36 women were
      included in the study out of which 16 women were diagnosed with primary
      unexplained infertility and the other 20 women with severe
      oligoasthenozoospermic/azoospermic male partners. Both groups were sub-divided
      into three groups; women stimulated with letrozole, or with CC, and the third
      group was allowed to ovulate spontaneously (natural cycles). Women having natural
      cycles and not given any drug were considered as controls. Once ovulation was
      confirmed by ultrasonography, endometrial samples were collected on the seventh
      day post-ovulation and analyzed. In women with unexplained infertility treated
      with letrozole and CC, epithelial and stromal expression of alphavbeta3 integrin,
      L-selectin, leukemia inhibitory factor (LIF), and pinopod formation was found to
      be significantly higher as compared to controls. Expression of these receptivity
      markers was found to be comparable amongst the letrozole, CC, and control groups
      in women with severe oligoasthenozoospermic/azoospermic male partners. Cell cycle
      analysis showed similar cell cycle phase fractions on comparing the CC and the
      letrozole groups. Stimulation with letrozole and CC appears to enhance
      endometrial receptivity in women with unexplained infertility. However, letrozole
      and CC did not have any significant effect on the endometrial receptivity markers
      of women with severe oligoasthenozoospermic/azoospermic male partners.

PMID- 24304328
TI  - Oxidative status shifts in uterine cervical incompetence patients.
AB  - Uterine cervical incompetence (UCI) is a pregnancy complication affecting about
      10% of the pregnancies in the western world. Studying the etiology of the UCI
      requires a specific approach adequate for this highly heterogenous syndrome.
      Oxidative status disorders are associated with various pathologies, including
      pregnancy complications. As such, general oxidative status profiling is a
      promising methodology to treat UCI. We aimed at assaying the closely interrelated
      oxidative status markers in the uterine cervical incompetence patients by means
      of the systems biology-oriented approach. Chemiluminescent assay, circulating
      thioredoxin 1 protein, uric acid, and homocysteine level measurements were used
      to assess the character of the oxidative status regulation in the UCI patients.
      We found UCI to be associated with the atypical plasma oxidative status
      deregulation; UCI plasma samples demonstrated lowered proneness to the pro
      oxidative processes, and this was not due to the excessive antioxidant activity.
      There were neither signs of oxidative stress nor destructive pro-oxidant
      feedforward circuit locking in the UCI group. We also report increased
      circulating levels of uric acid in the UCI patients.

PMID- 24304329
TI  - Oxygen isotope composition of trinitite postdetonation materials.
AB  - Trinitite is the melt glass produced subsequent the first nuclear bomb test
      conducted on July 16, 1945, at White Sands Range (Alamagordo, NM). The geological
      background of the latter consists of arkosic sand that was fused with radioactive
      debris and anthropogenic materials at ground zero subsequent detonation of the
      device. Postdetonation materials from historic nuclear weapon test sites provide
      ideal samples for development of novel forensic methods for attribution and
      studying the chemical/isotopic effects of the explosion on the natural geological
      environment. In particular, the latter effects can be evaluated relative to their
      spatial distribution from ground zero. We report here delta(18)O(0/00) values for
      nonmelted, precursor minerals phases (quartz, feldspar, calcite), "feldspathic
      rich" glass, "average" melt glass, and bulk (natural) unmelted sand from the
      Trinity site. Prior to oxygen isotope analysis, grains/crystals were examined
      using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy
      (EDS) to determine their corresponding major element composition. delta(18)O
      values for bulk trinitite samples exhibit a large range (11.2-15.50/00) and do
      not correlate with activity levels for activation product (152)Eu; the latter
      levels are a function of their spatial distribution relative to ground zero.
      Therefore, the slow neutron flux associated with the nuclear explosion did not
      perturb the (18)O/(16)O isotope systematics. The oxygen isotope values do
      correlate with the abundances of major elements derived from precursor minerals
      present within the arkosic sand. Hence, the O isotope ratios documented here for
      trinitite melt glass can be attributed to a mixture of the respective signatures
      for precursor minerals at the Trinity site prior to the nuclear explosion. 

PMID- 24304330
TI  - Investigation of 5-HT3A receptor gene expression in peripheral blood mononuclear
      cells of individuals who had been exposed to air pollution.
AB  - The role of air pollution in exacerbation of allergic symptoms is well known.
      Several studies have shown the effect of air pollution on serotonergic system.
      The changes in serotonergic system could trigger several allergic symptoms. 5
      HT(3A) is among serotonin receptors on the peripheral Blood Mononuclear Cells
      (PBMCs) as well as other cells. In the present study we compared the 5-HT(3A)
      gene expression in PBMCs of the asthmatic patients as well as individuals who had
      been exposed to the air pollution. Normal individuals were also included in the
      study as control for comparison of 5-HT(3A) gene expression. Following the
      synthesis of the cDNA using mRNA extracted from PBMCs the level of 5- HT(3A) gene
      expression was measured using real-time PCR. The results showed t a significant
      increase in the relative expression level of 5-HT(3A) receptor in PBMCs from
      asthmatic patients and individuals exposed to the air pollutants compared to
      normal controls. Our result indicates that significant increase in 5-HT(3A)
      receptor may contribute to the pathogenesis as well as allergic symptoms which
      resulted from air pollution.

PMID- 24304331
TI  - Impact of altered early infant gut microbiota following breastfeeding and
      delivery mode on allergic diseases.
AB  - The prevalence of allergic diseases among infants is increasing particularly in
      developed countries. Although, the exact reason is not clear yet, one of the most
      probable explanations is reducing microbial exposure during early life and
      consequent alteration of gut microbiota. Various factors including delivery mode,
      infant's diet, environment and antibiotics administration by mothers are involved
      in microbial colonization of infant's intestine. Since the content of infant'gut
      microbiota plays a critical role in the maturation and development of the immune
      system, it determines the risk of immune diseases. Different studies confirmed
      the important role of vaginal delivery, due to transferring of useful bacteria to
      the neonatal's intestine, and breastfeeding, owing to the presence of exosomes
      and different kind of mediators in the milk which modify the pattern of
      intestinal microflora. As a result, it was proposed that both factors have
      remarkable effects on reducing allergic diseases. Furthermore, the consumption of
      probiotic productions by the mother during and after pregnancy possibly induces
      beneficial impacts on attenuating the allergic diseases. 

PMID- 24304332
TI  - Long-term multimodal therapy (verapamil associated with propolis, blueberry,
      vitamin E and local diclofenac) on patients with Peyronie's disease (chronic
      inflammation of the tunica albuginea). Results of a controlled study.
AB  - OBJECTIVE: to demonstrate the possible effectiveness of a long-term multimodal
      medical therapy in patients with Peyronie's disease (PD) we carried out a
      controlled study on 82 patients diagnosed with PD, whereas in the scientific
      literature the conservative treatment of this disease is much discussed. METHODS:
      82 patients (mean age=53.6+/-10.1 years-range 23-68) diagnosed with PD were
      selected for this study. Of these 41 patients (group A) were treated for 18
      months as follows: Verapamil penile injections (12 total injections for six
      months and subsequently every month for twelve months: total 24 injections) +
      Iontophoresis with Verapamil/daily + blueberries 160mg/daily + propolis
      600mg/daily + Vitamin E 600mg/daily + topical Diclofenac/daily. The other 41
      patients spontaneously decided not to receive treatment for several motives and
      then were introduced as a control group B. All patients were controlled at 6- and
      18-month follow up with the same diagnostic tests completed before the therapy
      (penile ultrasound, photograph documentation, pain scale etc.). RESULTS: In group
      A, after treatment of 6 and 18 months, the change in plaque volume consisted in
      volume reduction= - 47.6% and -73.6% respectively, while in group B, the change
      consisted of an increase in plaque volume= +55.7% and +118.7% respectively
      (p=0.000). In group A, after treatment of 6 and 18 months, improvement of
      curvature occurred in 76.3% and 81.5% of the cases respectively, while in group B
      it occurred in 2.7% and 8.1%, respectively (p<0.0001). CONCLUSION: Our results
      showed that a long-term multimodal medical therapy (Verapamil associated with
      Antioxidants and local Diclofenac) is statistically effective to treat PD
      patients, if we consider that lower therapeutic outcomes were achieved after 6
      months treatment (medium-term treatment). Furthermore, this study confirms that
      the best treatment modality for PD is a combination therapy.

PMID- 24304334
TI  - Use of the international classification of functioning, disability and health as
      a framework for transition from paediatric to adult healthcare.

PMID- 24304333
TI  - Acute and chronic mu opioids differentially regulate thrombospondins 1 and 2
      isoforms in astrocytes.
AB  - Chronic opioids induce synaptic plasticity, a major neuronal adaptation.
      Astrocyte activation in synaptogenesis may play a critical role in opioid
      tolerance, withdrawal, and dependence. Thrombospondins 1 and 2 (TSP1/2) are
      astrocyte-secreted matricellular glycoproteins that promote neurite outgrowth as
      well as dendritic spine and synapse formation, all of which are inhibited by
      chronic MU opioids. In prior studies, we discovered that the mechanism of TSP1
      regulation by MU opioids in astrocytes involves crosstalk between three different
      classes of receptors, MU opioid receptor, EGFR and TGFbetaR. Moreover, TGFbeta1
      stimulated TSP1 expression via EGFR and ERK/MAPK activation, indicating that EGFR
      is a signaling hub for opioid and TGFbeta1 actions. Using various selective
      antagonists, and inhibitors, here we compared the mechanisms of chronic opioid
      regulation of TSP1/2 isoform expression in vivo and in immortalized rat cortical
      astrocytes. TSP1/2 release from astrocytes was also monitored. Acute and chronic
      MU opioids, morphine, and the prototypic MU ligand, DAMGO, modulated TSP2 protein
      levels. TSP2 but not TSP1 protein content was up-regulated by acute (3 h)
      morphine or DAMGO by an ERK/MAPK dependent mechanism. Paradoxically, TSP2 protein
      levels were altered neither by TGFbeta1 nor by astrocytic neurotrophic factors,
      EGF, CNTF, and BMP4. TSP1/2 immunofluorescence was increased in astrocytes
      subjected to scratch-wounding, suggesting TSPs may be useful markers for the
      "reactive" state of these cells and potentially for different types of injury.
      Previously, we determined that chronic morphine attenuated both neurite outgrowth
      and synapse formation in cocultures of primary astrocytes and neurons under
      similar temporal conditions that MU opioids reduced TSP1 protein levels in
      astrocytes. Here we found that, after the same 8 day treatment, morphine or DAMGO
      diminished TSP2 protein levels in astrocytes. Therefore, MU opioids may deter
      synaptogenesis via both TSP1/2 isoforms, but by distinct mechanisms. 

PMID- 24304335
TI  - Takotsubo syndrome resulting from urosepsis, or urinary catheter insertion?

PMID- 24304336
TI  - Simple identification of Trichophyton tonsurans by chlamydospore-like structures
      produced in culture media.
AB  - Trichophyton tonsurans is known to be the causative agent of a worldwide epidemic
      of dermatophytoses among contact sports practitioners, and is spreading among the
      general population of Japan. Prompt and simple identification of T. tonsurans in
      diagnostic laboratories is crucial to control infection. The present study
      evaluated the availability of observation of chlamydospore-like structures grown
      in culture media as a characteristic for identification of T. tonsurans. Twenty
      five strains of T. tonsurans and five strains each of Trichophyton verrucosum,
      Trichophyton rubrum and Trichophyton mentagrophytes were inoculated on Mycosel
      agar plates and inoculated Petri dishes were observed by light microscopy from
      the reverse side. Twenty-three of 25 T. tonsurans strains showed chlamydospore
      like structures within 5 days, and all strains at day 8. The numbers of
      chlamydospore-like structures were very abundant in most strains. The majority of
      strains of other species showed no chlamydospore-like structures, or very few
      when present. Positive for chlamydospore-like structures among 15 strains other
      than T. tonsurans was one strain at day 5 and six strains at day 8. As for the
      identification of T. tonsurans, presence of chlamydospore-like structures showed
      92.0% sensitivity (23/25) and 93.3% specificity (14/15) at day 5, and 100%
      sensitivity (25/25) and 60.0% specificity (9/15) at day 8. Electron microscopic
      findings suggest chlamydospore-like structures are not true chlamydospores but
      are produced by inflation of actively growing hyphae by developing vacuoles in
      cells. In conclusion, observation of development of chlamydospore-like structures
      in culture media is the simplest method for identification of T. tonsurans. 

PMID- 24304338
TI  - Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals:
      stereoelectronic role of trans effect in a metal-mediated pericyclic process and
      a shift from homogeneous to heterogeneous catalysis during a one-pot reaction.
AB  - The combination of experiments and computations reveals unusual features of
      stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into
      (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into
      allene aldehydes, proceeds under homogeneous conditions via a "cyclization
      mediated" mechanism initiated by Rh(I) coordination at the alkyne. This path
      agrees well with the small experimental effects of substituents on the carbinol
      carbon. The key feature revealed by the computational study is the
      stereoelectronic effect of the ligand arrangement at the catalytic center. The
      rearrangement barriers significantly decrease due to the greater transfer of
      electron density from the catalytic metal center to the CO ligand oriented trans
      to the alkyne. This effect increases electrophilicity of the metal and lowers the
      calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads
      to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective
      tautomerization. The intermediacy of heterogeneous catalysis by nanoclusters was
      confirmed by mercury poisoning, temperature-dependent sigmoidal kinetic curves,
      and dynamic light scattering. The combination of experiments and computations
      suggests that the initially formed allene-aldehyde product assists in the
      transformation of a homogeneous catalyst (or "a cocktail of catalysts") into
      nanoclusters, which in turn catalyze and control the stereochemistry of
      subsequent transformations. 

PMID- 24304337
TI  - Visible and invisible caring in nursing from the perspectives of patients and
      nurses in the gerontological context.
AB  - AIM: Just as in many countries all over the world, the number of older people in
      Italy has increased rapidly. Consequently, an increasing number of nurses are
      engaged in the care of older patients. However, due to a lack of understanding of
      how nurses and patients perceive caring, nursing care may be compromised. The aim
      of this study is to explore, describe and compare the perceptions of
      gerontological nurses and patients related to the dimensions of caring in nursing
      in an Italian hospital setting. METHODS: In this qualitative descriptive study, a
      variety of analytic techniques were used to analyse semi-structured interview
      data from a purposeful sample of 20 nurses and 20 patients from geriatric units
      in two different Italian hospitals. FINDINGS: Although both nurses and patients
      gave rich descriptions of caring experiences, patients described features of
      caring in nursing that were visible (including nurses' caring gestures, giving
      attention and being competent) while nurses predominantly emphasised aspects of
      caring that were relatively invisible (such as reflecting on the patient's past
      needs, evaluating the nursing care rendered, planning for more appropriate future
      nursing care, taking multiple complex contextual factors into account to protect
      the patient and being competent). CONCLUSION: Our data revealed more nuanced
      insight into the meaning of invisible and visible caring in nursing within the
      gerontological context than has been previously reported in the literature. This
      has implications for nursing education and practice because it may help nurses
      meet the actual needs of older patients in hospital settings.

PMID- 24304339
TI  - Polymerization shrinkage and depth of cure of bulk fill flowable composite
      resins.
AB  - OBJECTIVE: To evaluate polymerization shrinkage and depth of cure of two bulk
      fill flowable composites, one nanohybrid composite modified to a flowable
      consistency, and one standard flowable composite, comparing the scraping method
      to the Knoop hardness test. METHODS: Two bulk fill flowable composites, SureFil
      SDR flow (SSF) (Dentsply) and Venus Bulk Fill (VBF) (Heraeus Kulzer), one
      standard flowable, Filtek Supreme Ultra Flowable (FSUF) (3M/ESPE) (control), and
      one regular bulk composite that can be made flowable, SonicFill (SF) (Kerr), were
      used in this study. For polymerization shrinkage (PS), ten 2-mm samples were made
      for each composite and cured for 20 seconds and shrinkage was measured with a
      Kaman linometer. For hardness, ten specimens of each composite were made in a 10
      * 10-mm mold and cured for 20 seconds; the bottom surface was scraped according
      to ISO 4049 specification, and the remaining thickness was measured with a
      micrometer. Hardness samples were prepared at 2-, 3-, 4-, and 5-mm thick *14-mm
      diameter, cured for 20 seconds, and polished. After 24 hours of dry storage, a
      Knoop indenter was applied at 100 g load for 11 seconds. Three readings were made
      on the top and bottom of each specimen and averaged for each surface to calculate
      a Knoop hardness value and a bottom/top hardness ratio. One-way analysis of
      variance and Tukey tests were used to determine significant differences between
      thicknesses and between test methods for each material. RESULTS: PS values were
      3.43 +/- 0.51%, 3.57 +/- 0.63%, 4.4 +/- 0.79%, and 1.76 +/- 0.53% for FSUF, SSF,
      VBF, and SF, respectively. VBF showed significantly greater shrinkage (4.4 +/-
      0.79%), followed by FSUF (3.43 +/- 0.51%) and SSF (3.57 +/- 0.63%), which were
      similar, and SF (1.76 +/- 0.53%), which had significantly less shrinkage
      (p<0.05). Values for the scraping method for depth of cure were significantly
      greater for SSF and VBF (>5.0 mm), followed by SF (3.46 +/- 0.16 mm) and FSU
      (2.98 +/- 0.22 mm). Knoop top hardness values (KHN) were: VBF 21.55 +/- 2.39,
      FSUF 44.62 +/- 1.93, SSF 29.17 +/- 0.76, and SF 72.56 +/- 2.4 at 2 mm and were
      not significantly different at 3-, 4-, and 5-mm thick within each material.
      Ratios for bottom/top values (depth of cure) for 2, 3, 4, and 5 mm were: VBF 0.80
      +/- 0.1, 0.78 +/- 0.03, 0.67 +/- 0.10, and 0.59 +/- 0.07, respectively; SSF 0.74
      +/- 0.08, 0.72 +/- 0.08, 0.69 +/- 0.18, and 0.62 +/- 0.08, respectively; SF 0.82
      +/- 0.05, 0.68 +/- 0.05, 0.47 +/- 0.04, and 0.21 +/- 0.02, respectively; and FSUF
      0.56 +/- 0.08 at 2 mm and 0.40 +/- 0.08 at 3 mm. The bottom/top ratio was .80 or
      less at all depths and decreased below 0.70 at 4-mm depth for VBF and SSF, at 3
      mm for SF and at 2 mm for FSUF.

PMID- 24304340
TI  - Degree of conversion and hardness of a silorane-based composite resin: effect of
      light-curing unit and depth.
AB  - PURPOSE: To investigate the effect of different light-curing units and depths on
      the degree of conversion (DC) through Fourier transform infrared spectroscopy
      (FTIR) and Knoop Hardness Number (KHN) of a silorane-based composite resin
      (Filtek LS, 3M ESPE, St Paul, MN, USA) (LS). MATERIALS AND METHODS: LS specimens
      mounted in a particular designed matrix were photoactivated by three light-cure
      units (LCUs) at depths of 2, 3, 4, and 5 mm. The DC was determined in a FTIR
      spectrometer with an attenuated total reflectance accessory. The KHN was measured
      in an automatic microhardness tester. The results were analyzed using the
      Friedman and Spearman statistical tests (alpha=0.05). RESULTS: There was no
      effect of LCUs on the DC (p=0.472) or KHN (p=0.174) for all of the studied
      depths. The highest DC and KHN means were found at 2-mm depth, which were not
      statistically different from 3-mm depth, but were higher than 4-mm and 5-mm
      depths (p=0.007). Spearman analysis found a positive linear correlation between
      the variables KHN and DC (r=0.858, p<0.000). CONCLUSIONS: The LCUs' effect was
      not verified. Values of DC and KHN for LS decreased with increasing depth. The
      highest values for both DC and KHN were obtained at depths of 2-3 mm.

PMID- 24304341
TI  - Effect of toothbrushing-mouthrinse-cycling on surface roughness and topography of
      nanofilled, microfilled, and microhybrid resin composites.
AB  - The purpose of this study was to evaluate the influence of toothbrushing
      mouthrinse-cycling (TMC) on the surface roughness and topography of three resin
      composites with different filler particle systems (Z350, nanofilled [Nf];
      Durafill, microfilled [Mf], and Empress Direct, microhybrid [Mh]). Twenty
      specimens of each resin composite (8.0 mm diameter and 2 mm height) were randomly
      divided into four groups (n=5) according to the mouthrinses: alcohol-free (Plax-
      P) and alcohol-containing (Listerine--L and Plax Fresh Mint--PM) and artificial
      saliva (control--AS). The specimens were submitted to TMC for nine weeks. A
      surface roughness tester and a three-dimensional profilometer were used to
      measure the roughness (Ra) and the topography (Sa) before and after TMC. The data
      were analyzed by multifactor analysis of variance and Tukey post hoc test
      (alpha=0.05). In all media, Mh presented greater roughness than Mf (p<0.05). The
      highest value of roughness was presented by Mh immersed in L (p<0.05). The lowest
      values of roughness were presented by Mf (p<0.05). The three resin composites
      presented the highest roughness after immersion in mouthrinses containing alcohol
      (PM and L) (p<0.05). For the three resin composites, the increase in roughness
      was noticeable after the fifth week. Topographic analysis showed that the
      smoothest surfaces were present after immersion in AS.

PMID- 24304342
TI  - Risk predictive modelling for diabetes and cardiovascular disease.
AB  - Absolute risk models or clinical prediction models have been incorporated in
      guidelines, and are increasingly advocated as tools to assist risk stratification
      and guide prevention and treatments decisions relating to common health
      conditions such as cardiovascular disease (CVD) and diabetes mellitus. We have
      reviewed the historical development and principles of prediction research,
      including their statistical underpinning, as well as implications for routine
      practice, with a focus on predictive modelling for CVD and diabetes. Predictive
      modelling for CVD risk, which has developed over the last five decades, has been
      largely influenced by the Framingham Heart Study investigators, while it is only
      ~20 years ago that similar efforts were started in the field of diabetes.
      Identification of predictive factors is an important preliminary step which
      provides the knowledge base on potential predictors to be tested for inclusion
      during the statistical derivation of the final model. The derived models must
      then be tested both on the development sample (internal validation) and on other
      populations in different settings (external validation). Updating procedures
      (e.g. recalibration) should be used to improve the performance of models that
      fail the tests of external validation. Ultimately, the effect of introducing
      validated models in routine practice on the process and outcomes of care as well
      as its cost-effectiveness should be tested in impact studies before wide
      dissemination of models beyond the research context. Several predictions models
      have been developed for CVD or diabetes, but very few have been externally
      validated or tested in impact studies, and their comparative performance has yet
      to be fully assessed. A shift of focus from developing new CVD or diabetes
      prediction models to validating the existing ones will improve their adoption in
      routine practice.

PMID- 24304343
TI  - Ergonomic vs. ergonomics: acknowledging the etymology.

PMID- 24304345
TI  - Understanding selectin counter-receptor binding from electrostatic energy
      computations and experimental binding studies.
AB  - Higher organisms defend themselves against invading micro-organisms and harmful
      substances with their immune system. Key players of the immune system are the
      white blood cells (WBC), which in case of infection move in an extravasation
      process from blood vessels toward infected tissue promoting inflammation. This
      process starts with the attachment of the WBC to the blood vessel wall, mediated
      by protein pair interactions of selectins and counter-receptors (C-R). Individual
      selectin C-R binding is weak and varies only moderately between the three
      selectin types. Multivalency enhances such small differences, rendering selectin
      binding type specific. In this work, we study selectin C-R binding, the initial
      step of extravasation. We performed electrostatic energy computations based on
      the crystal structure of one selectin type co-crystallized with the ligating part
      of the C-R. The agreement with measured free energies of binding is satisfactory.
      Additionally, we modeled selectin mutant structures in order to explain
      differences in binding of the different selectin types. To verify our modeling
      procedures, surface plasmon resonance data were measured for several mutants and
      compared with computed binding affinities. Binding affinities computed with
      soaked rather than co-crystallized selectin C-R structures do not agree with
      measured data. Hence, these structures are inappropriate to describe the binding
      mode. The analysis of selectin/C-R binding unravels the role played by individual
      molecular components in the binding event. This opens new avenues to prevent
      immune system malfunction, designing drugs that can control inflammatory
      processes by moderating selectin C-R binding. 

PMID- 24304346
TI  - Temporal variation of a protein folding energy landscape in the cell.
AB  - Chemical reaction rate coefficients and free energies are usually time
      independent quantities. Protein folding in vitro is one such reaction with a
      fixed energy landscape. However, in the milieu of the cell, the energy landscape
      can be modulated in space and time by fluctuations in the intracellular
      environment such as cytoskeletal rearrangements, changes in biomolecule
      concentrations, and large scale cellular reorganization. We studied the time
      dependence of the folding landscape of a FRET-labeled enzyme, yeast
      phosphoglycerate kinase (PGK-FRET). Living U2OS cells served as our test tube,
      and the mammalian cell cycle, a process strictly regulated in time, served as our
      clock. We found that both the rate of folding and the thermodynamic stability of
      PGK-FRET are cell cycle-dependent. We also assayed folding rates of PGK-FRET in
      spatial proximity to and far away from mitotic chromosomes. Our results show that
      expedited folding in DNA-rich regions cannot account for the faster rate of PGK
      FRET folding in mitotic cells. 

PMID- 24304347
TI  - In vitro antiplasmodial activity, cytotoxicity and chemical profiles of sponge
      species of Cuban coasts.
AB  - Aqueous and organic fractions from the crude extracts of 17 sponge species
      collected at Boca de Calderas, Havana, Cuba were analysed. The organic fractions
      of Mycale laxissima, Clathria echinata and Agelas cerebrum exhibited values of
      concentrations causing 50% inhibition of in vitro growth of Plasmodium berghei
      (IC50) of 42.3 +/- 5.1, 52 +/- 9.7 and 60.3 +/- 10.6 MUg/mL, respectively, while
      their selectivity indexes for fibroblast cell lines were 9.45, 4.24 and 8.7,
      correspondingly. These fractions reduced parasitemia of infected Balb/c mice as
      well. Selective cytotoxicity indexes against tumour HeLa cells focused an
      interest on the aqueous fraction of M. laxissima (>7.12) and organic fractions of
      Polymastia nigra (5.95), A. cerebrum (5.48) and Niphates erecta (>4.2).
      Triterpenoids/steroids and alkaloids detected in the organic fractions of M.
      laxissima, C. echinata and A. cerebrum should be isolated for future
      investigation.

PMID- 24304348
TI  - Synthesis and structure-activity relationship of 3-hydroxypyridine-2-thione-based
      histone deacetylase inhibitors.
AB  - We previously identified 3-hydroxypyridine-2-thione (3HPT) as a novel zinc
      binding group for histone deacetylase (HDAC) inhibition. Early structure-activity
      relationship (SAR) studies led to various small molecules possessing selective
      inhibitory activity against HDAC6 or HDAC8 but devoid of HDAC1 inhibition. To
      delineate further the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi),
      we have extended the SAR studies to include the linker region and the surface
      recognition group to optimize the HDAC inhibition. The current efforts resulted
      in the identification of two lead compounds, 10d and 14e, with potent HDAC6 and
      HDAC8 activities that are inactive against HDAC1. These new HDACi possess
      anticancer activities against various cancer cell lines including Jurkat J.gamma1
      for which SAHA and the previously disclosed 3HPT-derived HDACi were inactive. 

PMID- 24304349
TI  - Treatment retention, drug use and social functioning outcomes in those receiving
      3 months versus 1 month of supervised opioid maintenance treatment. Results from
      the Super C randomized controlled trial.
AB  - AIM: Supervised consumption of opioid maintenance treatment (OMT) is standard in
      many drug centres reducing drug diversion, but is costly. We aimed to determine
      whether supervised consumption of OMT improved retention and other measures of
      drug use. DESIGN: Pragmatic randomized controlled trial comparing 3 months of
      daily supervised consumption of OMT with 1 month or less of daily supervised OMT,
      then daily unsupervised consumption. SETTING: Four community drug services in the
      United Kingdom. PARTICIPANTS: A total of 293 opioid-dependent patients entering
      OMT. MEASUREMENTS:  PRIMARY OUTCOME: retention in treatment at 12 weeks.
      Secondary: retention at 6 months; illicit drug use [Maudsley Addiction Profile
      (MAP)]; quality of life (SF-12 and MAP); criminality (MAP); and social
      functioning. FINDINGS: No significant between-group difference was observed for
      the primary outcome: 69% (100 of 145) supervised and 74% (109 of 148)
      unsupervised were retained [odds ratio (OR) = 0.74, 95% confidence interval (CI)
      = 0.43-1.27]. Per protocol survival analysis suggested that supervised patients
      were less well retained (hazard ratio for retention = 0.71, 95% CI = 0.51-1.00).
      Illicit opioid use reduced in both groups and, while not statistically
      significant by intention-to-treat analysis, favoured unsupervised patients in per
      protocol analysis (odds of positive opioid screen for supervised versus
      unsupervised = 2.07, 95% CI = 1.05-4.06). Data on criminal activity also favoured
      unsupervised patients with 21% supervised patients committing crime versus 9%
      unsupervised (OR = 3.37, 95% CI = 1.28-8.86). CONCLUSIONS: There was no evidence
      of a difference in treatment retention or opioid use rates between patients whose
      consumption of opioid maintenance treatment was supervised for 3 months daily
      (except Saturdays) compared with supervision for 1 month. There was some evidence
      that longer periods of supervised consumption were associated with higher levels
      of criminality.

PMID- 24304350
TI  - Apoptotic events induced by maleimides on human acute leukemia cell lines.
AB  - Cyclic imides are known for their antitumor activity, especially the
      naphthalimide derivatives, such as Mitonafide and Amonafide. Recently, we have
      demonstrated the cytotoxic effect of a series of naphthalimide derivatives
      against B16F10 melanoma cells. On the basis of this fact, we have developed a
      study starting from the synthesis of different cyclic imides and the evaluation
      of their cytotoxic properties on human acute leukemia cells (K562 and Jurkat).
      Initially, a screening test was conducted to select the compound with the best
      cytotoxic effect, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay. After this selection, structural modifications were performed in
      the most active compound to obtain five more derivatives. All compounds presented
      a good cytotoxic effect. The results of cell cycle analysis, fluorescence
      microscopy, and Annexin V-FITC assay confirmed that the cells observed in the sub
      G0/G1 phase were undergoing apoptosis. From this set of results, cyclic imides 8,
      10, and 12 were selected for the evaluation of the mechanisms involved in the
      apoptotic process. The results demonstrate the involvement of the intrinsic
      pathway of apoptosis, evidenced by the reduction in mitochondrial potential, an
      increase in the level of AIF protein expression, a decreased level of expression
      of anti-apoptotic Bcl-2 protein, and an increased level of expression of pro
      apoptotic protein Bax in both K562 and Jurkat cells treated with cyclic imides
      (8, 10, and 12). Furthermore, cyclic imides 8 and 10 caused an increase in the
      level of Fas expression in Jurkat cells, indicating the additional involvement of
      the extrinsic apoptosis pathway. The compounds (8, 10, and 12) also caused a
      decreased level of expression of anti-apoptotic protein survivin. The biological
      effects observed with these cyclic imide derivatives in this study suggest
      promising applications against acute leukemia. 

PMID- 24304351
TI  - X-ray magnetic circular dichroism investigation of the electron transfer
      phenomena responsible for magnetic switching in a cyanide-bridged [CoFe] chain.
AB  - The cyanide-bridged [CoFe] one-dimensional chain, [Co(II)((R)
      pabn)][Fe(III)(Tp)(CN)3](BF4).MeOH.2H2O, where (R)-pabn = (R)-N2,N(2')
      bis(pyridin-2-ylmethyl)-1,1'-binaphthyl-2,2'-diamine and Tp =
      hydrotris(pyrazolyl)borate, exhibits magnetic and electric bistabilities
      originating from an electron transfer coupled spin transition between Fe-CN-Co
      pairs. The use of L-edge X-ray absorption spectroscopy (XAS) in combination with
      L-edge X-ray magnetic circular dichroism (XMCD) is explored for the investigation
      of the electronic structure and magnetization of Co and Fe ions separately, in
      both diamagnetic and paramagnetic states. It has been established from
      susceptibility results that the switching between diamagnetic and paramagnetic
      phases emanates from electron transfer between low spin Fe(II) and Co(III),
      resulting in low spin Fe(III) (S = 1/2) and high spin Co(II) (S = 3/2). The XAS
      and XMCD results are consistent with the bulk susceptibility measurements, where
      greater detail regarding the charge transfer process is determined. The Fe-CN-Co
      electron transfer pathway is highlighted by a strongly XMCD dependent transition
      to a cyanide back bonding orbital, giving evidence for strong hybridization with
      Fe(III) t2g orbitals. In addition to thermally induced and photoinduced
      switching, [CoFe] is found to exhibit a switching by grinding induced
      dehydration. Analysis of XAS shows that on grinding diamagnetic [CoFe], 75% of
      metal ions lock into the magnetic Co(II)Fe(III) phase. Density functional theory
      calculations based on the [CoFe] crystal structure in the magnetic and
      nonmagnetic phases aid the spectroscopic results and provide a complementary
      insight into the electronic configuration of the [CoFe] 3d shells, quantifying
      the change in ligand field around Co and Fe centers on charge transfer. 

PMID- 24304352
TI  - Considerations on the mechanism of action of artemisinin antimalarials: part 1-
      the 'carbon radical' and 'heme' hypotheses.
AB  - The isolation of artemisinin from the traditional medicinal herb qing hao
      (Artemisia annua), its characterization as a peroxide and preparation of the
      derivatives dihydroartemisinin, artemether and artesunate in the 1970s and 1980s
      by Chinese scientists under the umbrella of Project 523 collectively represents
      one of the great events in medicine in the latter third of the 20(th) Century.
      Artemisinins have become the most important component of chemotherapy of malaria:
      although used initially in monotherapy, they are now used in combination
      therapies or ACTs with longer half-life quinolines or arylmethanols.
      Nevertheless, the recent emergence of artemisinin-tolerant strains of the malaria
      parasite as reflected in increased clearance times of parasitaemia in patients
      treated with ACTs represents the greatest threat to control of malaria since
      resistance to chloroquine was first reported over 55 years ago. Importantly, the
      event brings into sharp focus the realization that relatively little is precisely
      understood, as opposed to widely assumed, for the mechanism of drug action of
      artemisinins and their synthetic peroxide analogues. Thus, we review here their
      antimalarial activities, the use of artemisinins in combination therapies, drug
      drug interactions with the quinolines and arylmethanols, and metabolism of the
      artemisinins and synthetic peroxides. The mechanism of action of quinolines and
      arylmethanols, in particular their ability to induce redistribution of heme into
      the parasite cytosol, is also highlighted. This collective information is then
      used as a counterpoint to screen the validity of two of the prevailing hypotheses
      of drug action of artemisinins and synthetic peroxides, namely i. 'the C-radical
      hypothesis' wherein the peroxide undergoes 'bioactivation' by ferrous iron to
      generate C-radicals that are held to be the cytotoxic agents and ii. the 'heme
      hypothesis' wherein ferrous heme may generate either the same type of 'cytotoxic'
      C-radical, or the peroxide forms heme adducts that apparently inherit the
      exquisite cytotoxicities of the parent peroxide in one way or another. In a
      subsequent review, we screen the third and fourth hypotheses: the SERCA
      hypothesis wherein artemisinins modulate operation of the malaria parasite
      sarcoendo plasmic reticulum calcium pump SERCA Ca(2+)-ATPase ATP6 and the co
      factor hypothesis wherein artemisinins act as oxidant drugs through rapidly
      oxidizing reduced conjugates of flavin cofactors, or those of flavin cofactor
      precursors such as riboflavin, and other susceptible endogenous substrates that
      play a role in maintaining intraparasitic redox homeostasis. For the C-radical
      hypothesis, details of in vitro chemical studies in the context of established
      chemistry of C-radicals and their ability to react with radical trapping agents
      such as nitroso compounds, cyclic nitrones, persistent nitroxyl radicals and
      atmospheric oxygen (dioxygen) are summarized. Overall, there is no correlation
      between antimalarial activities and abilities of the derived C-radicals to react
      with trapping agents in a chemical flask. This applies in particular to the
      reactions of C-radicals from artemisinins and steroidal tetraoxanes with the
      trapping agents vis-a-vis those from adamantyl capped systems. In an
      intraparasitic medium, it is not possible to intercept C-radicals either through
      use of a vast excess of a nitroxyl radical or dioxygen. The lack of correlation
      of antimalarial activities also applies to the Fe(2+)-mediated decomposition of
      artemisinins and synthetic peroxides, where literature data taken as indicating
      otherwise are critically assessed. The antagonism to antimalarial activities of
      artemisinins exerted by desferrioxamine (DFO) and related Fe(3+)-chelating agents
      is due to formation of stable chelates with bioavailable Fe(3+) that shuts down
      redox cycling through Fe(2+) and the subsequent generation of reactive oxygen
      species (ROS) via the Fenton reaction. The generation of ROS by Fe(2+)
      complements the action of artemisinins, to be discussed in Part 2; there is no
      need to posit a reaction of Fe(2+) with the artemisinins to account for their
      antimalarial activity. The ability of artemisinins and synthetic peroxides to
      elicit membrane damage is examined in the light of established processes of
      autoxidation. The oxidant character of the intraparasitic environment is
      incompatible with the reducing conditions required for generation of C-radicals,
      and in contrast to the expectation raised by the C-radical hypothesis, and indeed
      by the heme hypothesis outlined below, antimalarial activities of artemisinins
      are enhanced under higher partial pressures of dioxygen. Structure-activity data
      from a wide variety of artemisinins and synthetic peroxides cannot be
      accommodated within the bounds of the C-radical hypothesis. Finally, the
      antimalarial Cradical construct sharply contrasts with that of the potently
      antitumour-active ene-diyne antibiotics such as neocarzinostatin. In an iron-free
      process, these compounds generate highly reactive aryl C-radicals that abstract H
      atoms from deoxyribose units in DNA to generate alkyl C-radicals. The last do
      react with dioxygen in a normal intracellular environment to initiate DNA strand
      cleavage. Overall, it must be concluded that the C-radical hypothesis as the
      basis for antimalarial activities of artemisinins and synthetic peroxides is
      untenable. Heme has been intensively studied as an 'activator' of artemisinins
      and other antimalarial peroxides, and indeed the hypothesis seemingly has become
      firmly embedded in the underlying brickwork of the scientific edifice. The locus
      of activity of the peroxides interacting with the heme is considered to be the
      parasite digestive vacuole. The basis for the nanomolar activities of
      artemisinins and synthetic peroxides is variously ascribed to heme-Fe(2+)
      mediated generation of C-radicals from the peroxides, formation of heme
      artemisinin adducts that are held either to engage in redox cycling with
      concomitant generation of ROS or to inhibit formation of hemozoin. In the last
      case, just like the aminoquinolines and arylmethanols, the peroxides are not the
      active agents, but exert their parasiticidal effects through allowing the build
      up of free heme-Fe(3+), the ultimate cytotoxic entity. We assess the literature
      relating to generation of heme by hemoglobin digestion, and the stage at which
      this process becomes significant in the intraerythrocytic parasite. The claims of
      production of heme and conversion into hemozoin occurring in a lipid environment
      may have to be put aside based on recent literature data that indicates
      crystallization of hemozoin must take place an aqueous interface; association of
      lipids with the heme/hemozoin is likely to be a reflection of attractive van der
      Waals interactions involving the hydrophobic surface of the heme or hemozoin
      aggregates. In addition, the observation leading to the claim that hemozoin
      manufacture commences at the mid-ring stage cannot be independently verified.
      That the quinoline and arylmethanol antimalarials have essentially no activities
      on the ring stage parasites and exert greatest efficacy at the trophozoite stage
      where heme production is maximal is consistent with this. Conversely,
      artemisinins, and indeed redox active drugs such as methylene blue and others,
      are highly active against early ring stage parasites. Thus, there is a prominent
      disconnect between stage specificities of artemisinins vis-a-vis those of 4
      aminoquinolines and arylmethanols suggesting that heme is not the target of the
      former class of drug. Further, the ability of the Fe(3+) chelate DFO to
      antagonize antimalarial activities of artemisinins, but not the activities of 4
      aminoquinolines, cannot be explained by involvement of heme as a target for
      artemisinins. We critically examine the basis for formation of products obtained
      from reaction of heme with artemisinins and synthetic peroxides under conditions
      ranging from biomimetic - reactions employing catalytic reagents under aqueous or
      semi-aqueous conditions - to those conducted under highly reducing and eminently
      artificial conditions, usually in the solvent dimethyl sulfoxide (DMSO) that both
      forms well characterized complexes with heme-Fe(2+) and actually assists in
      driving single electron transfer processes. It is noted that alkylated products
      tend to form in high yields under the last conditions, and this aspect is readily
      explained. Irrespective of product yields obtained under various conditions, an
      overarching correlation between facility of the reaction of the peroxide with
      heme and their antimalarial activities does not exist. The is underscored by the
      reproducible outcomes of reactions conducted under biomimetic conditions
      indicating adducts cannot form in physiologically meaningful concentrations and
      that heme is a recalcitrant reaction partner to artemisinins in general. Again,
      as in the case of the C-radical hypothesis, structure-activity data from a wide
      variety of artemisinins and synthetic peroxides is difficult to reconcile with
      the heme hypothesis. This applies in particular to dimeric and trimeric
      artemisinin derivatives where the ascribing of biological activity to reactions
      of the derived radicals or to the vastly encumbered artemisinin-heme adducts is
      physically unrealistic. Finally, the facile metabolism and induction of
      metabolism of the current clinically used artemisinins by members of the CYP
      superfamily - heme proteins that require an intimate interaction of the heme with
      the artemisinin for metabolism to occur - is incompatible with the oft-cited
      proclivity of the peroxide to associate via complex formation with heme as a
      prelude to its 'activation' as an antimalarial agent within the malaria parasite.
      (ABSTRACT TRUNCATED)

PMID- 24304353
TI  - Tuberculosis vaccines: hopes and hurdles.
AB  - Tuberculosis (TB) remains as one of the most serious public health problems
      worldwide. It is one of the main causes of death in poor and developing
      countries, especially in sub-Saharan Africa, where it may be associated with the
      human immunodeficiency virus (HIV). It has been estimated that one third of the
      world population is infected by Mycobacterium tuberculosis (Mtb), and there were
      about 8.7 million new TB cases, and about 1.4 million yearly deaths due to TB in
      2011. DOTS is the currently used drug therapy in TB but there is non-compliance
      which results in emergence of resistance. Bacille Calmette Guerin (BCG), an
      attenuated vaccine derived from Mycobacterium bovis, is the only licensed TB
      vaccine, but not recommended in HIV-infected infants. There are 14 vaccine
      candidates that have entered clinical trials and over 35 candidates in discovery
      and preclinical development. Mycobacterium indicus pranii [Mw; MIP] and M. vaccae
      are in phase III clinical trial and the Drug Controller of India licensed MIP for
      human use in India. 

PMID- 24304354
TI  - Is Helicobacter pylori the infectious trigger for headache?: A review.
AB  - The interest that surrounds the bacterium Helicobacter pylori (H. pylori) is due
      not only to its causal role in several gastroduodenal diseases, but also to its
      supposed involvement in the pathogenesis of extra-gastric manifestations. This
      review provides a literature update on the hypothetic correlation between H.
      pylori and headache. To identify all publications on this issue, a MEDLINE search
      of all studies published in English from 1965 to 2013 was conducted. The authors
      examined three aspects of this potential association: epidemiology, intervention
      trials and pathogenesis. While in the former, the results are contradictory, in
      the intervention studies, it has been documented that at 6 and 12 months,
      bacterial eradication is associated to disappearance of symptoms in 23% and 28%
      of cases, and to a significant decrease of intensity, frequency and duration of
      acute attacks in the remaining patients. Under a pathogenetic aspect, if H.
      pylori has a role, it does not act through oxidative stress. In conclusion, the
      eradication of H. pylori seems efficient at least in a subgroup of patients
      suffering from migraine. Further investigations should focalize on particular
      subgroups of patients and, encouraged from data produced by intervention studies,
      evaluate the long-term benefit of eradication. 

PMID- 24304355
TI  - Discovering and developing new medicines for malaria control and elimination.
AB  - A steady increase in the number of antimalarial drug candidates since 2007
      follows a call to eradicate malaria from the World Health Organization (WHO), the
      Bill and Melinda Gates Foundation and others. Four new fixed dose combination
      medicines have been approved by stringent authorities or the WHO in as many
      years. OZ439, a synthetic endoperoxide currently in Phase II, could reduce
      treatment to a single dose. Significant challenges remain: while drugs to treat
      patients suffering from malaria are essential, drugs focused on breaking the
      lifecycle between human and mosquito host are needed. Effective medicines that
      are easy to take in the field are needed, together with treatments for infants
      and for women in the first trimester of pregnancy. Research has concentrated on
      Plasmodium falciparum infection but there is a need for medicines that prevent
      relapses of P. vivax infection. In addition, the evolution of pathogen resistance
      against established drugs poses a threat to existing medicines. Direct testing of
      compounds against whole parasites as well as target approaches has accelerated
      the process of drug discovery, and identified new classes of compounds. The most
      advanced of these, spiroindolone, already in clinical development, kills the
      blood stages of both P. falciparum and P. vivax by a mechanism unrelated to any
      current antimalarial. The collaborative model of drug discovery between the
      Medicines for Malaria Venture, pharmaceutical companies and academic institutions
      has resulted in the construction of a promising pipeline of new classes of
      compounds, focused on the needs of the patient. 

PMID- 24304356
TI  - Malaria in children--prevention and management.
AB  - Malaria causes a quarter of all childhood deaths in Sub-Saharan Africa.
      Considerable gains in global malaria control have been achieved in the last
      decade but coverage of effective interventions remains low in areas of greatest
      malaria burden. Some countries have achieved reduced malaria related mortality
      through application of recent advances in malaria prevention and treatment of
      children. Artemisinin combination therapies (particularly artesunate) are highly
      efficacious and well-tolerated in children, although several alternative
      treatments are available. However, the evolution of drug resistance (including
      emerging resistance to artemisinin derivatives) threatens the success of malaria
      treatment programmes. This special issue review is aimed at paediatric clinicians
      in resource-poor settings and provides a summary of recent data from paediatric
      trials of malaria treatment and prevention interventions. 

PMID- 24304357
TI  - Noma and cervicofacial necrotizing fasciitis: clinicopathological differentiation
      and an illustrative case report of noma.
AB  - Noma predominantly affects malnourished young children. The pathogenesis of noma
      is complex and multifactorial, involving interaction between local polybacterial
      infection on the one hand, and malnutrition, immunosuppression, or systemic
      bacterial or viral infections on the other hand. Noma is considered to be an
      opportunistic disease, but the immediate cause is uncertain. Immunosuppression
      associated with a high HIV load may be an important risk factor in South Africa.
      Cervicofacial necrotizing fasciitis, on the other hand, occurs mainly in adults.
      It is frequently a consequence of an odontogenic infection and is characterized
      by an irregular pattern of rapidly spreading necrosis of fascia, muscle, and
      skin. We present an unusual case of noma in a 32-year-old malnourished HIV
      seropositive female with AIDS in whom, within a period of 3 days, the initial
      intraoral necrotizing process spread rapidly and caused circular full thickness
      perforating destruction of the lower lip. Prompt diagnosis and treatment brought
      about control of the active disease and limited the extension of the established
      noma and of progression of the disease at other affected oral sites.

PMID- 24304358
TI  - The Imbalance of Th17 cells and CD4(+) CD25(high) Foxp3(+) Treg cells in patients
      with atopic dermatitis.
AB  - BACKGROUND: Th17/Treg imbalance is involved in several autoimmune, inflammatory
      and allergic reactions. Nevertheless, the possible contribution of Th17/Treg
      imbalance in atopic dermatitis (AD) remains unknown. OBJECTIVE: To explore the
      possible role of Th17/Treg imbalance in AD. METHODS: Th17 and Treg cells
      percentage in peripheral blood mononuclear cells (PBMCs) and skin specimens,
      specific transcription factor retinoic acid-related orphan receptor (ROR)gammat
      and Foxp3 mRNA levels in PBMCs, as well as Th17- and Treg-related cytokines mRNA
      levels in PBMCs, serum concentrations, and expression levels in PBMCs culture
      supernatant after recombinant Dermatophagoides pteronyssinus antigen stimulation
      were detected in AD patients. Controls included patients with psoriasis, allergic
      contact dermatitis (ACD) and healthy donors. RESULTS: Th17 cells percentage,
      RORgammat, IL-17 and IL-23 levels in peripheral circulation of AD patients were
      significantly higher than those in ACD patients and healthy controls, but lower
      than those of psoriasis patients. Treg cells percentage, Foxp3 and TGF-beta mRNA
      levels were reduced in AD patients compared with healthy controls, while there
      were no significant differences among AD, ACD and psoriasis patients. Th17 cells
      percentage, IL-17 and IL-23 levels were increased, while Treg cells percentage
      and TGF-beta level were decreased in AD lesion and PBMCs culture supernatant
      respectively. There was a negative association between Th17 and Treg cells
      percentage in AD patients. AD severity score positively correlated with Th17
      cells percentage and Th17/Treg ratio, while negatively correlated with Treg cells
      percentage. Serum IgE levels positively correlated with Th17/Treg ratio.
      CONCLUSION: In AD, there exists an immune imbalance in Th17 and Treg cells, which
      may contribute to its pathogenesis and development.

PMID- 24304359
TI  - Scalar position in cochlear implant surgery and outcome in residual hearing and
      the vestibular system.
AB  - OBJECTIVE: To evaluate the effect of the intracochlear electrode position on the
      residual hearing and VNG- and cVEMP responses. DESIGN: Prospective pilot study.
      STUDY SAMPLE: Thirteen adult patients who underwent unilateral cochlear implant
      surgery were examined with high-resolution rotational tomography after cochlear
      implantation. All subjects were also tested with VNG, and 12 of the subjects were
      tested with cVEMP and audiometry before and after surgery. RESULTS: We found that
      although the electrode was originally planned to be positioned inside the scala
      tympani, only 8 of 13 had full insertion into the scala tympani. Loss of cVEMP
      response occurred to the same extent in the group with full scala tympani
      positioning and the group with scala vestibuli involvement. There was a non
      significant difference in the loss of caloric response and residual hearing
      between the two groups. Interscalar dislocation of the electrode inside the
      cochlea was observed in two patients. A higher loss of residual hearing could be
      seen in the group with electrode dislocation between the scalae. CONCLUSIONS: Our
      findings indicate that intracochlear electrode dislocation is a possible cause to
      loss of residual hearing during cochlear implantation but cannot be the sole
      cause of postoperative vestibular loss.

PMID- 24304360
TI  - Thresholds for vestibular-evoked myogenic potentials (VEMPs) produced by
      impulsive transmastoid acceleration.
AB  - OBJECTIVE: To evaluate methods for estimating thresholds of vestibular evoked
      myogenic potentials (VEMPs) and ocular VEMPs (OVEMPs) produced by impulsive
      transmastoid acceleration (ITA). DESIGN: VEMPs and OVEMPs were obtained
      simultaneously from subjects in supine posture with both head and eyes elevated.
      Thresholds to ITA were measured using four different response identification
      methods. STUDY SAMPLE: Twelve adult subjects with no history of auditory or
      vestibular deficits. RESULTS: VEMP and OVEMP thresholds were found within the
      range of -8 to -26 dB re 0.2 g, with overall VEMP thresholds being lower than
      OVEMP thresholds by average of 3-10 dB, depending on the method used. CONCLUSION:
      VEMPs can be obtained at lower ITA stimulation levels than OVEMPs. Threshold
      values depend on the method used to define response presence.

PMID- 24304361
TI  - Folic acid-conjugated, SERS-labeled silver nanotriangles for multimodal detection
      and targeted photothermal treatment on human ovarian cancer cells.
AB  - The effectiveness of a therapeutic agent for cancer stands in its ability to
      reduce and eliminate tumors without harming the healthy tissue nearby.
      Nanoparticles peripherally conjugated with targeting moieties offer major
      improvements in therapeutics through site specificity. In this study we
      demonstrate this approach by targeting the folate receptor of NIH:OVCAR-3 human
      ovary cancer cell line. Herein we used silver nanotriangles which were
      biocompatibilized with chitosan (bio)polymer, labeled with para-aminothiophenol
      (pATP) Raman reporter molecule, and conjugated with folic acid. The nanoparticles
      conjugation and efficient labeling was investigated by localized surface plasmon
      resonance (LSPR), zeta potential, and surface-enhanced Raman scattering (SERS)
      measurements. Conjugated particles were proven to be highly stable in aqueous and
      cellular medium. The targeted uptake of conjugated nanoparticles by human ovary
      cancer cells was confirmed by dark field microscopy and scattering spectra of the
      particles inside cells. Comparative studies revealed specific internalization of
      the conjugated nanoparticles in comparison with similar bare nanoparticles.
      Moreover, the SERS identity of the particles was proven to be highly conserved
      inside cells. Targeted cancer cell treatment conducted by irradiating the
      nanoparticle-treated cells with a continuous wave-nearinfrared (cw-NIR) laser in
      resonance with their plasmonic band proved an efficient therapeutic response. By
      integrating the advantages of multimodal optical imaging and SERS detection with
      hyperthermia capabilities through site specificity, these nanoparticles can
      represent a real candidate for personalized medicine. 

PMID- 24304362
TI  - Locked planarity: a strategy for tailoring ladder-type pi-conjugated anilido
      pyridine boron difluorides.
AB  - A novel series of syn- and anti-ladder-type anilido-pyridine boron difluorides
      (APBDs) were synthesized by stepwise incorporation of boron into laddered
      ligands. The boron coordination-locked strategy endows the ladder-type APBDs with
      a stiff conformation, which results in a substantial bathochromic shift of their
      absorption spectra and a narrowed HOMO-LUMO energy gap, reinforcing the compounds
      for potential applications in organic electronics. 

PMID- 24304363
TI  - Effects of transcutaneous tibial nerve stimulation on anorectal physiology in
      fecal incontinence: a double-blind placebo-controlled cross-over evaluation.
AB  - BACKGROUND: Transcutaneous electrical tibial nerve stimulation (TENS) is of
      growing interest for the treatment of fecal incontinence (FI), but its mechanism
      of action remains uninvestigated. We aimed to further assess the anorectal
      response to TENS in a dynamic model. METHODS: We performed a placebo-controlled,
      randomized, double-blinded crossover study in 19 patients suffering from FI to
      assess the effects of TENS on anorectal function. Anorectal physiology and
      perception were recorded through two sequences of rectal isobaric distension
      using an electronic barostat device to measure anal and rectal pressures, rectal
      volumes, and perception scores. KEY RESULTS: Maximal rectal pressure and volume
      variation were affected by TENS, with higher mean maximal rectal pressure (5.33
      and 4.06 mmHg in the active and sham TENS respectively, p < 0.0001) and lower
      volume variation (11.45 and 14.7 mL in the active and sham stimulation
      respectively, p < 0.05). Rectal compliance was not modified by active TENS.
      Pressure of the upper anal canal was significantly lower with raised isobaric
      distension in sequences assigned to active TENS. CONCLUSIONS & INFERENCES: Acute
      TENS modified anorectal physiology by strengthening the myogenic response to
      distension rather than increasing muscle relaxation and related rectal compliance
      in patients with FI.

PMID- 24304365
TI  - Assessment of right ventricular function by transthoracic echocardiography
      following aortic valve replacement.
AB  - BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is a widely used
      clinical measure of right ventricular (RV) systolic performance. However,
      postsurgical changes in the pattern of RV contraction may limit the utility of
      TAPSE for assessing global RV function. We retrospectively examined pre- and
      postoperative TAPSE and RV fractional area change (FAC) in patients undergoing 3
      different types of aortic valve replacement (AVR). METHODS: Fifty-two patients
      enrolled in the Placement of AoRTic TraNscathetER Valve Trial at our institution
      were randomized to receive open AVR or transcatheter AVR (TAVR) by either the
      transapical or transfemoral access routes. Thirty-seven of these patients had
      analyzable transthoracic echocardiography (TTE) before and after AVR. Using M
      mode echocardiography, TAPSE was measured in the apical four-chamber view. Using
      two-dimensional echocardiography, RV FAC was measured in the apical four-chamber
      view. RESULTS: The mean change in TAPSE was -0.7 +/- 0.6 cm for open AVR (P =
      0.002), -0.2 +/- 0.4 cm for transapical TAVR (P = 0.26), and 0.1 +/- 0.5 cm for
      transfemoral TAVR (P = 0.64). The mean change in RV FAC was -1 +/- 5% for open
      AVR (P = 0.91), 2 +/- 4% for transapical TAVR (P = 0.37), and 7 +/- 10% for
      transfemoral TAVR (P = 0.07). CONCLUSIONS: The normal pattern of RV contraction
      was unchanged by transapical and transfemoral TAVR, while open AVR led to a
      significant decrease in TAPSE with preserved RV FAC. Thus, RV FAC is a preferable
      method for assessing RV function in the postoperative patient.

PMID- 24304364
TI  - Modelling longitudinal changes in older adults' memory for spoken discourse:
      findings from the ACTIVE cohort.
AB  - Episodic memory shows substantial declines with advancing age, but research on
      longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is
      limited. Using parallel process latent growth curve models, we examined 10 years
      of longitudinal data from the no-contact control group (N = 698) of the Advanced
      Cognitive Training for Independent and Vital Elderly (ACTIVE) randomised
      controlled trial in order to test (1) the degree to which SDM declines with
      advancing age, (2) the predictors of these age-related declines and (3) the
      within-person relationship between longitudinal changes in SDM and longitudinal
      changes in fluid reasoning and verbal ability over 10 years, independent of age.
      Individuals who were younger, were White, had more years of formal education,
      were male and had better global cognitive function and episodic memory
      performance at baseline demonstrated greater levels of SDM on average. However,
      only age at baseline uniquely predicted longitudinal changes in SDM, such that
      declines accelerated with greater age. Independent of age, within-person decline
      in reasoning ability over the 10-year study period was substantially correlated
      with decline in SDM (r = .87). An analogous association with SDM did not hold for
      verbal ability. The findings suggest that longitudinal declines in fluid
      cognition are associated with reduced spoken language comprehension. Unlike
      findings from memory for written prose, preserved verbal ability may not protect
      against developmental declines in memory for speech.

PMID- 24304367
TI  - Effectiveness of adalimumab for refractory serpiginous choroiditis.

PMID- 24304366
TI  - Mesenchymal stem cells seeded on cross-linked and noncross-linked acellular
      porcine dermal scaffolds for long-term full-thickness hernia repair in a small
      animal model.
AB  - Biological meshes are biomaterials consisting of extracellular matrix that are
      used in surgery particularly for hernia treatment, thoracic wall reconstruction,
      or silicone implant-based breast reconstruction. We hypothesized that combination
      of extracellular matrices with autologous mesenchymal stem cells used for hernia
      repair would result in increased vascularization and increased strength of
      incorporation. We cultured autologous adipose-derived stem cells harvested from
      the inguinal region of Wistar rats on cross-linked and noncross-linked porcine
      extracellular matrices. In 24 Wistar rats, a standardized 2*4 cm fascial defect
      was created and repaired with either cross-linked or noncross-linked grafts
      enriched with stem cells. Non-MSC-enriched grafts were used as controls. The rats
      were sacrificed at 3 months of age. The specimens were examined for the strength
      of incorporation, vascularization, cell invasion, foreign body reaction, and
      capsule formation. Both materials showed cellular ingrowth and
      neovascularization. Comparison of both tested groups with the controls showed no
      significant differences in the capsule thickness, foreign body reaction,
      cellularization, or vascularization. The strength of incorporation of the stem
      cell-enriched cross-linked extracellular matrix specimens was higher than in
      acellular specimens, but this result was statistically nonsignificant. In the
      noncross-linked extracellular matrix, the strength of incorporation was
      significantly higher in the stem cell group than in the acellular group. Seeding
      of biological meshes with stem cells does not significantly contribute to their
      increased vascularization. In cross-linked materials, it does not ensure
      increased strength of incorporation, in contrast to noncross-linked materials.
      Owing to the fact that isolation and seeding of stem cells is a very complex
      procedure, we do not see sufficient benefits for its use in the clinical setting.

PMID- 24304368
TI  - Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis.
AB  - Leg ulcers are often complicated in patients with rheumatoid arthritis (RA),
      however, the etiology is multifactorial. We examined the cases of leg ulceration
      or gangrene in seven RA patients who were hospitalized over the past 3 years. One
      patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was
      suspected in three patients, no histological evidence was obtained from the skin
      specimens. In these patients, angiography revealed the stenosis or occlusion of
      digital arteries. In the remaining three patients, leg ulcers were considered to
      be due to venous insufficiency. Treatment should be chosen depending on the
      causes of leg ulcers. 

PMID- 24304369
TI  - Ni/CdS bifunctional Ti@TiO2 core-shell nanowire electrode for high-performance
      nonenzymatic glucose sensing.
AB  - In this work, a Ni/CdS bifunctional Ti@TiO2 core-shell nanowire electrode with
      excellent electrochemical sensing property was successfully constructed through a
      hydrothermal and electrodeposition method. Field emission scanning electron
      microscopy (FESEM) and transmission electron microscopy (TEM) were employed to
      confirm the synthesis and characterize the morphology of the as-prepared samples.
      The results revealed that the CdS layer between Ni and TiO2 plays an important
      role in the uniform nucleation and the following growth of highly dispersive Ni
      nanoparticle on the Ti@TiO2 core-shell nanowire surface. The bifunctional
      nanostructured electrode was applied to construct an electrochemical nonenzymatic
      sensor for the reliable detection of glucose. Under optimized conditions, this
      nonenzymatic glucose sensor displayed a high sensitivity up to 1136.67 MUA mM(-1)
      cm(-2), a wider liner range of 0.005-12 mM, and a lower detection limit of 0.35
      MUM for glucose oxidation. The high dispersity of Ni nanoparticles, combined with
      the anti-poisoning faculty against the intermediate derived from the self
      cleaning ability of CdS under the photoexcitation, was considered to be
      responsible for these enhanced electrochemical performances. Importantly,
      favorable reproducibility and long-term performance were also obtained thanks to
      the robust frameworks. All these results indicate this novel electrode is a
      promising candidate for nonenzymatic glucose sensing. 

PMID- 24304370
TI  - Exploring caregiving experiences: caregiver coping and making sense of illness.
AB  - OBJECTIVES: The current research explores how family caregivers (1) make sense of
      caregiving and (2) cope with their circumstance. METHOD: We analysed
      semistructured interviews of 13 caregivers of people with either stroke (n = 5)
      or dementia (n = 8) and used photographs that caregivers took exemplifying their
      caregiving experiences to elicit their description of how they made sense of
      caregiving. This enabled greater insight into caregivers' perspective of
      caregiving complementing our use of Interpretative Phenomenological Analysis
      (IPA) to analyse verbatim transcripts. RESULTS: Emerging themes included (1)
      making sense of illness including the implications of receiving a diagnosis,
      caregiving motivations and receiving support, and (2) coping with caregiving,
      with variance in coping depending on, in part, individual differences in sense
      making. Caregivers adopted active and information seeking techniques to deal with
      current problems and to increase their sense of control, but avoidant techniques
      when considering future logistics of caregiving and when feeling helpless due to
      the burden they faced. At times caregivers looked on the bright side and made
      downward comparisons. CONCLUSION: The combination of elicitation techniques and
      analysis using IPA established patterns across caregivers and individual
      differences between caregivers in the meaning they assigned to their caregiving
      experience. Differences in sense making were based on the context of the
      caregiving stressor, which in turn influenced the variability in caregiver's
      coping techniques adopted. The analysis detailed within this article provides
      evidence that information and service provision must be tailored to individual
      caregiver experiences.

PMID- 24304371
TI  - Unusual plaque and papules affecting the legs.

PMID- 24304372
TI  - Polycomb protein EZH2 expression in diffuse large B-cell lymphoma is associated
      with better prognosis in patients treated with rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone.
AB  - Polycomb group (PcG) proteins are evolutionarily conserved regulators of gene
      expression that contribute to normal lymphocyte development, and are involved in
      malignant transformation of these cells. Recently, BMI1 and EZH2 have been shown
      to be involved in lymphomagenesis and oncogenesis. We tried to elucidate the role
      of EZH2 as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). High
      level expression of EZH2 (EZH2 >= 70%) was associated with superior overall
      survival (OS) of 85.8% compared to low expression (EZH2 < 70%), with OS of 44.5%
      (p = 0.005). Subgroup analysis showed that the activated B-cell (ABC) subtype
      with high EZH2 expression had the highest overall survival (p = 0.011). In
      analysis of EZH2 expression within low International Prognostic Index (IPI)
      score, high EZH2 expression had a significant statistical correlation with longer
      OS (p = 0.034). With high IPI score, high EZH2 expression tended to be associated
      with longer OS (p = 0.130). Our results showed that EZH2 expression had a high
      prognostic relevance to survival outcomes. We demonstrated that DLBCL was
      associated with increased expression of the EZH2 PcG protein and Ki67. The
      distribution of EZH2 expression was wider than that of Ki67. In summary,
      increased EZH2 expression of tumor cells was associated with improvements in OS.

PMID- 24304373
TI  - Prominent hematogone hyperplasia in BCR-ABL1-positive chronic myelogenous
      leukemia: mimicking recurrent B-lymphoid blast crisis.

PMID- 24304374
TI  - The use of a fludarabine-based conditioning regimen in patients with severe
      aplastic anemia--a retrospective analysis from three Indian centers.
AB  - Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent
      hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of
      fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA
      identical sibling or family donors. Seventy-six patients were considered "high
      risk" as per criteria. The graft source included peripheral blood stem cells in
      109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of
      cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two
      had graft failure and two expired in the first two wk. Neutrophil engraftment was
      seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d
      (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in
      8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall
      survival for the entire cohort is 75.8 +/- 3.9% with a survival of 95.6 +/- 3.1%
      in the low-risk group (n = 45) and 64.0 +/- 5.6% in the high-risk group (n = 76).
      Conditioning with fludarabine and cyclophosphamide is associated with very good
      long-term survival in patients undergoing HSCT for SAA.

PMID- 24304375
TI  - Limited benefit of pentostatin salvage therapy for steroid-refractory grade III
      IV acute graft-versus-host disease.
AB  - Corticosteroid-refractory (SR) acute graft-versus-host disease (aGVHD) remains a
      major cause of morbidity and mortality after allogeneic hematopoietic cell
      transplantation. Multiple agents have been evaluated in this setting, but the
      benefit of pentostatin has not been described well. We report a single-center
      experience of pentostatin salvage therapy for SR aGVHD. Fifteen patients received
      pentostatin for SR aGVHD from March 2005 till March 2010 after failure to respond
      to methylprednisolone >= 2 mg/kg/d for at least seven d. All patients had grade
      III-IV aGVHD prior to pentostatin therapy. Thirteen (87%), 10 (67%), and six
      (40%) patients had gastrointestinal (GI), skin, and liver involvement of aGVHD,
      respectively. Pentostatin was given at a median of 33 d after steroid therapy
      initiation. The dose of pentostatin was 1.4 mg/m(2) daily for three d, repeated
      every two wk. Eight (53%) patients also received additional therapies. Complete
      responses were noted in two patients (both in skin). However, one patient
      relapsed and did not respond to additional salvage treatment. Partial responses
      were seen in three patients. Fourteen died of GVHD-related causes. This study
      suggested that pentostatin is of limited benefit in the treatment for SR grade
      III-IV aGVHD.

PMID- 24304376
TI  - Tolerability of sirolimus: a decade of experience at a single cardiac transplant
      center.
AB  - Sirolimus is used in cardiac transplant recipients to prevent rejection,
      progression of cardiac allograft vasculopathy, and renal dysfunction. However,
      sirolimus has many potential side effects and its tolerability when used outside
      of clinical trials is not well established. We describe a decade of experience
      with sirolimus in cardiac transplant recipients at our institution. We
      retrospectively reviewed records of all adult cardiac transplant recipients
      living between September 1999 and February 2010 (n = 329) and identified 67
      patients (20%) who received sirolimus. The indications for sirolimus were cardiac
      allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and
      intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus
      at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70%
      of subjects experienced an adverse event attributed to sirolimus. Adverse events
      were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p
      = 0.004). We conclude that sirolimus is frequently used in cardiac transplant
      recipients (20%) and commonly causes side effects, often necessitating
      discontinuation. Higher average sirolimus levels were associated with adverse
      events, suggesting that tolerability may improve if levels are maintained within
      the lower end of the current therapeutic range; however, the improvement in
      tolerability would need to be balanced with the potential for decreased efficacy.

PMID- 24304377
TI  - Urine free light chains as a novel biomarker of acute kidney allograft injury.
AB  - BACKGROUND: We evaluated urine free light chains (FLC) as a potential biomarker
      for acute kidney allograft injury (AKAI). METHODS: Urine kappa and lambda FLC
      were compared with urine beta-2 microglobulin (beta2-M), retinol-binding protein
      (RBP), kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated
      lipocalin (NGAL), and microalbuminuria (MAB) in biopsy-confirmed acute rejection
      (AR) and acute tubular necrosis (ATN). Healthy volunteers (normal) and transplant
      recipients with normal allograft function (control) were used as references.
      RESULTS: Compared with control or normal group (N = 15), urine FLC, MAB, and RBP
      were higher in ATN (N = 29) and AR (N = 41) groups (p < 0.05). There was no
      difference in KIM-1, NGAL, or beta2-M between four groups. In the AR group, urine
      kappaFLC demonstrated the highest predictive value with sensitivity of 95.12% and
      specificity of 87.5% (p < 0.0001). Urine kappaFLC also performed best with a
      sensitivity of 96.55% and specificity of 93.33% (p < 0.0001) in the ATN group.
      The area under the receiver operating characteristic (ROC) curves (AUC) by ROC
      analysis is greatest in urine RBP (100%) and FLC (99%), and lowest in KIM-1
      (53.5%), then NGAL (71.5%) in the AR group. The AUC is also greatest in urine FLC
      (100%) and RBP (99%), and lowest in urine KIM-1 (55.6%) and NGAL (69.9%) in the
      ATN group. CONCLUSIONS: Urine FLC appears sensitive for both AR and ATN, and it
      may be a novel AKAI biomarker.

PMID- 24304378
TI  - Rituximab is associated with improved survival in cardiac allograft patients with
      antibody-mediated rejection: a single center review.
AB  - Antibody-mediated rejection (AMR) after cardiac transplantation is associated
      with significant mortality, and the optimal treatment of this condition is poorly
      defined. Rituximab has been used successfully for the treatment for antibody
      mediated diseases; however, its role in AMR is unclear. We review our experience
      with rituximab in patients with cardiac allograft AMR. We conducted a
      retrospective analysis of cardiac transplant patients with a diagnosis of AMR
      from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with
      the presence of C4d complement staining on endomyocardial biopsy and the absence
      of cellular rejection of grade 2R or greater. Patients were divided into
      Rituximab and NoRituximab groups. The primary endpoint was all-cause mortality.
      Secondary endpoints were infection, change in ejection fraction (EF), and
      rehospitalization. Thirty-three patients met inclusion criteria, of whom 13
      received rituximab and 20 did not. Baseline characteristics were similar between
      groups. Kaplan-Meier curves for a three-yr follow-up period demonstrate improved
      survival in the Rituximab group (p = 0.0089). There were no differences in
      secondary endpoints. We found that rituximab therapy was associated with improved
      survival in cardiac allograft AMR. Further prospective, randomized studies in
      larger patient populations are needed to confirm this finding and to define ideal
      timing for rituximab administration.

PMID- 24304379
TI  - Comprehensive health assessment and five-yr follow-up of allogeneic islet
      transplant recipients.
AB  - In patients with type 1 diabetes mellitus (T1DM) complicated by severe
      hypoglycemic episodes, fear of hypoglycemia can significantly impact daily life.
      We evaluated whether restoration of glycemic awareness and prevention of
      hypoglycemia by islet allotransplant could reduce fear and improve health status.
      We conducted a comprehensive evaluation of patient-based outcomes in 48 T1DM
      subjects screened for allogeneic islet transplant alone (ITA) and 27 subjects who
      received an ITA. A battery of generic health status and diabetes-specific
      measures were used to assess ITA at evaluation, six months, and then annually
      after ITA. Allogeneic islet transplant was associated with a reduction in
      behaviors adopted in avoiding hypoglycemia (p Value < 0.001) and attenuation in
      concerns about hypoglycemic episodes (p Value < 0.001). Changes in hypoglycemia
      fear tracked most closely with insulin use. While there was a trend toward global
      improvement in health as measured by the EQ-5D (p Value = 0.002) and in
      depression symptoms as measured by the Beck (p Value = 0.003), physical health
      remained unchanged following ITA. Our findings support the socioemotional
      benefits of ITA during the five years after ITA, which to some extent remains
      dependent on preservation of islet graft function.

PMID- 24304380
TI  - Estimation of the dietary intake of 13 priority additives in France, Italy, the
      UK and Ireland as part of the FACET project.
AB  - The aim of this study was to assess the dietary exposure of 13 priority additives
      in four European countries (France, Italy, the UK and Ireland) using the
      Flavourings, Additives and Contact Materials Exposure Task (FACET) software. The
      studied additives were benzoates (E210-213), nitrites (E249-250) and sulphites
      (E220-228), butylated hydroxytoluene (E321), polysorbates (E432-436), sucroses
      esters and sucroglycerides (E473-474), polyglycerol esters of fatty acids (E475),
      stearoyl-lactylates (E481-482), sorbitan esters (E493-494 and E491-495),
      phosphates (E338-343/E450-452), aspartame (E951) and acesulfame (E950). A
      conservative approach (based on individual consumption data combined with maximum
      permitted levels (Tier 2)) was compared with more refined estimates (using a
      fitted distribution of concentrations based on data provided by the food industry
      (Tier 3)). These calculations demonstrated that the estimated intake is below the
      acceptable daily intake (ADI) for nine of the studied additives. However, there
      was a potential theoretical exceedance of the ADI observed for four additives at
      Tier 3 for high consumers (97.5th percentile) among children: E220-228 in the UK
      and Ireland, E432-436 and E481-482 in Ireland, Italy and the UK, and E493-494 in
      all countries. The mean intake of E493-494 could potentially exceed the ADI for
      one age group of children (aged 1-4 years) in the UK. For adults, high consumers
      only in all countries had a potential intake higher than the ADI for E493-494 at
      Tier 3 (an additive mainly found in bakery wares). All other additives examined
      had an intake below the ADI. Further refined exposure assessments may be
      warranted to provide a more in-depth investigation for those additives that
      exceeded the ADIs in this paper. This refinement may be undertaken by the
      introduction of additive occurrence data, which take into account the actual
      presence of these additives in the different food groups. 

PMID- 24304381
TI  - Bottleable (amino)(carboxy) radicals derived from cyclic (alkyl)(amino) carbenes.
AB  - Monomeric (amino)(carboxy) radicals were synthesized in two steps: the addition
      of a stable cyclic (alkyl)(amino) carbene to an acyl chloride, followed by a one
      electron reduction. Their stability toward dimerization also allows for the
      synthesis of related bi- and triradicals. 

PMID- 24304382
TI  - Vascular endothelial growth factor signaling in injured nerves underlies
      peripheral sensitization in neuropathic pain.
AB  - Chronic neuroinflammation may be a critical component of intractable inflammatory
      diseases, including neuropathic pain. Because angiogenesis as a result of
      vascular endothelial growth factor (VEGF) signaling plays a pivotal role in
      inflammation, we focused on the mechanisms of VEGF-regulated neuropathic pain in
      mice. The mRNA and protein expression of VEGFA were up-regulated in the injured
      sciatic nerve after partial sciatic nerve ligation (PSL). VEGFA was localized to
      accumulated macrophages and neutrophils derived from bone marrow. Up-regulation
      of VEGFA was mediated by histone H3 acetylation and trimethylation in its
      promoter region. VEGF receptors (VEGFR1 and VEGFR2) were localized to vascular
      endothelial cells or macrophages. By ex vivo fluorescence imaging and
      immunohistochemistry using DiI fluorescence, progression of angiogenesis was
      observed in the injured sciatic nerve after PSL. Perineural administration of
      pharmacological inhibitors of VEGFA and VEGFR tyrosine kinases prevented tactile
      allodynia and thermal hyperalgesia caused by PSL. Moreover, we determined the
      contribution of VEGF- and CXC-chemokine receptor 4-expressing angiogenic
      macrophages to neuropathic pain. Taken together, VEGFA is up-regulated in injured
      peripheral nerves and participates in angiogenesis and prolonged pain behaviors
      through its receptors. We propose that VEGFA-related components may underlie
      peripheral sensitization leading to neuropathic pain. Angiogenesis due to VEGF
      signaling is a key component of chronic inflammation. VEGFA up-regulation and
      pathological angiogenesis were observed in the injured nerves in mice.
      Pharmacological inhibition of VEGF signaling suppressed neuropathic pain
      behaviors. Therefore, VEGFA-related components may underlie peripheral
      neuroinflammation leading to neuropathic pain. 

PMID- 24304383
TI  - New cytotoxic spirostane saponin and biflavonoid glycoside from the leaves of
      Acacia saligna (Labill.) H.L. Wendl.
AB  - New naturally occurring spirostane saponin (25S)-5beta-spirostan-3beta-yl-3-O
      beta-D-xylopyranosyl(1 -> 3)-O-beta-D-xylopyranosyl(1 -> 4)-beta-D
      galactopyranoside (6) and biflavonoid glycoside myricetin-3-O-rhamnoside (C7-O
      C7) myricetin-3-O-rhamnoside (4) along with a series of known compounds
      erythrodiol (1), 3beta-O-trans-p-coumaroyl-erythrodiol (2), quercetin-3-O-alpha-L
      rhamnoside (3) and myricetin-3-O-alpha-L-rhamnoside (5) were separated from the
      leaves of Acacia saligna (Labill.), H.L. Wendl. Compounds 1 and 2 were separated
      for the first time from genus Acacia. The structures of compounds 1-6 were
      established on the basis of extensive 1D and 2D NMR spectroscopic techniques in
      combination with EI-MS and HR-ESI-MS. These compounds were screened for their
      antioxidant and cytotoxic activities against HEPG2 (liver cancer) cell line and
      significant results were obtained.

PMID- 24304384
TI  - Revised coordination model and stability constants of Cu(II) complexes of tris
      buffer.
AB  - 2-Amino-2-hydroxymethyl-propane-1,3-diol, or tris(hydroxymethyl)aminomethane
      (Tris), is probably the most common biochemical buffer used alone or in
      combination with other buffers because it is stable, unreactive, and compatible
      with most proteins and other biomolecules. Being nontoxic, it has even found
      applications in medicine. Tris is known, however, to coordinate transition metal
      ions, Cu(II) among them. Although often ignored, this feature affects
      interactions of Cu(II) ions with biomolecules, as Tris is usually used in high
      molar excess. Therefore, it is important to have precise knowledge on the
      stoichiometry, stability, and reactivity of cupric Tris complexes. The literature
      data are incoherent in this respect. We reinvestigated the complex formation in
      the Tris-Cu(II) system by potentiometry, UV-vis, ESI-MS, and EPR at a broad range
      of concentrations and ratios. We found, contrary to several previous papers, that
      the maximum stoichiometry of Tris to Cu(II) is 2 and at neutral pH, dimeric
      complexes are formed. The apparent affinity of Tris buffer for Cu(II), determined
      by the competitivity index (CI) approach [Krezel, A.; Wojcik, J.; Maciejczyk, M.;
      Bal, W. Chem. Commun. 2003, 6, 704-705] at pH 7.4 varies between 2 * 10(6) and 4
      * 10(4) M(-1), depending on the Tris and Cu(II) concentrations and molar ratio. 

PMID- 24304385
TI  - Protease resistant variants of FGF1 with prolonged biological activity.
AB  - Therapeutic potential of human acidic fibroblast growth factor (FGF1) resulting
      from its undeniable role in angiogenesis and wound healing processes is
      questioned due to its low stability and short half-life in vivo. Our previous
      studies showed that prolonged biological activity of FGF1 can be achieved by
      increasing its proteolytic resistance directly linked to improved global
      thermostability. In this study, we applied an alternative method of generation of
      long-lasting FGF1 variants by rigidification of the growth factor's segment
      highly sensitive to proteases action. In order to determine regions the most
      prone to enzymatic degradation, we used limited proteolysis by trypsin combined
      with mass spectrometry analysis. We found that the initial proteolytic cleavages
      occurred mainly within the C-terminal region of the wild-type protein, pointing
      on its significant role in growth factor degradation. Based on bioinformatic
      analysis, we introduced two single mutations (C117P, K118V) within beta-strand XI
      and combined them in a double mutant. We determined resistance to proteolysis,
      biophysical properties and biological activities of obtained variants. All of
      them occurred to be significantly less susceptible to trypsin (up to 100-fold)
      and also to chymotrypsin degradation comparing to the wild-type protein.
      Interestingly, all variants were not more thermostable than the wild-type FGF1.
      We attributed this dramatic increase in resistance to proteolysis to entropic
      stabilization of C-terminal region. 

PMID- 24304386
TI  - Design of a peptide inhibitor of tyrosine kinase 2.
AB  - Tyrosine kinase inhibitors show great promise as clinical therapies, but small
      molecule inhibitors that are available in the clinic and under development bind
      to the adenosine triphosphate binding domain of the kinase, potentially limiting
      efficacy and selectivity. The development of antisense peptide inhibitors is a
      relatively unexplored area of research, and here we investigate inhibitory
      peptides specific for the Janus-associated kinase (JAK) family member, tyrosine
      kinase 2 (TYK2). We have developed peptides that are 2-3 times more selective for
      TYK2 than other JAK family members, with a TYK2 IC50 of 1.2 MUM. In addition,
      TYK2 inhibitory peptides show specificity for TYK2-mediated functions over JAK1
      functions in cell-based assays. These peptides provide a new tool for the
      development of specific peptide inhibitors for closely related tyrosine kinases. 

PMID- 24304387
TI  - Structure-activity relationships of chromone derivatives toward the mechanism of
      interaction with and inhibition of breast cancer resistance protein ABCG2.
AB  - We recently identified a chromone derivative, 5-(4-bromobenzyloxy)-2-(2-(5
      methoxyindolyl)ethyl-1-carbonyl)-4H-chromen-4-one, named here as chromone 1, as a
      potent, selective, nontoxic, and nontransported inhibitor of ABCG2-mediated drug
      efflux (Valdameri et al. J. Med. Chem. 2012, 55, 966). We have now synthesized a
      series of 14 derivatives to study the structure-activity relationships
      controlling both drug efflux and ATPase activity of ABCG2 and to elucidate their
      molecular mechanism of interaction and inhibition. It was found that the 4
      bromobenzyloxy substituent at position 5 and the methoxyindole are important for
      both inhibition of mitoxantrone efflux and inhibition of basal ATPase activity.
      Quite interestingly, methylation of the central amide nitrogen strongly altered
      the high affinity for ABCG2 and the complete inhibition of mitoxantrone efflux
      and coupled ATPase activity. These results allowed the identification of a
      critical central inhibitory moiety of chromones that has never been investigated
      previously in any series of inhibitors.

PMID- 24304388
TI  - In vitro and in vivo anti-inflammatory effects of a novel 4,6-bis ((E)-4-hydroxy
      3-methoxystyryl)-1-phenethylpyrimidine-2(1H)-thione.
AB  - Inflammation plays a critical defensive role in the human body. However,
      uncontrolled or aberrant inflammatory responses contribute to various acute and
      chronic diseases. The Nrf2-ARE pathway plays a pivotal role in the regulation of
      inflammatory markers, such as inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2). On the basis of this concept, we synthesized a novel
      anti-inflammatory 4,6-bis ((E)-4-hydroxy-3-methoxystyryl)-1-phenethylpyrimidine
      2(1H)-thione (HPT), and in vitro experiments using HepG2-C8 ARE-luciferase
      transfected cells demonstrated the induction of Nrf2-ARE activity. In
      lipopolysaccharide (LPS)-induced RAW 264.7 cells, HPT treatment reduced the
      production of nitric oxide (NO) as well as the protein and mRNA expression levels
      of COX-2 and iNOS, in a dose-dependent manner. In addition, HPT suppressed the
      mRNA expression of inflammatory cytokines, including tumor necrosis factor-alpha
      (TNF-alpha), interleukin (IL)-1beta, and IL-6. In LPS-induced macrophages, HPT
      inhibited COX-2 and iNOS by blocking the activation of p38 and c-Jun NH2-terminal
      kinase (JNK) but not extracellular signal-regulated kinase (ERK1/2). Furthermore,
      an in vivo anti-inflammatory study was performed using a TPA-induced skin
      inflammation mouse model, and the results showed that HPT reduced TPA-induced
      inflammation and attenuated the expression of COX-2 and iNOS in TPA-induced mouse
      skin tissue. Thus, HPT demonstrated anti-inflammatory activity both in LPS
      induced RAW 264.7 cells and TPA-stimulated mouse skin and may therefore serve as
      a potential anti-inflammatory agent. 

PMID- 24304389
TI  - Pathogenesis-related protein 4b interacts with leucine-rich repeat protein 1 to
      suppress PR4b-triggered cell death and defense response in pepper.
AB  - To control defense and cell-death signaling, plants contain an abundance of
      pathogen recognition receptors such as leucine-rich repeat (LRR) proteins. Here
      we show that pepper (Capsicum annuum) LRR1 interacts with the pepper pathogenesis
      related (PR) protein 4b, PR4b, in yeast and in planta. PR4b is synthesized in the
      endoplasmic reticulum, interacts with LRR1 in the plasma membrane, and is
      secreted to the apoplast via the plasma membrane. Binding of PR4b to LRR1
      requires the chitin-binding domain of PR4b. Purified PR4b protein inhibits spore
      germination and mycelial growth of plant fungal pathogens. Transient expression
      of PR4b triggers hypersensitive cell death. This cell death is compromised by co
      expression of LRR1 as a negative regulator in Nicotiana benthamiana leaves.
      LRR1/PR4b silencing in pepper and PR4b over-expression in Arabidopsis thaliana
      demonstrated that LRR1 and PR4b are necessary for defense responses to
      Pseudomonas syringae pv. tomato and Hyaloperonospora arabidopsidis (Hpa)
      infection. The mutant of the PR4b Arabidopsis ortholog, pr4, showed enhanced
      susceptibility to Hpa infection. Together, our results suggest that PR4b
      functions as a positive modulator of plant cell death and defense responses.
      However, the activity of PR4b is suppressed by interaction with LRR1.

PMID- 24304390
TI  - Status dystonicus: a practice guide.
AB  - Status dystonicus is a rare, but life-threatening movement disorder emergency.
      Urgent assessment is required and management is tailored to patient
      characteristics and complications. The use of dystonia action plans and early
      recognition of worsening dystonia may potentially facilitate intervention or
      prevent progression to status dystonicus. However, for established status
      dystonicus, rapidly deployed temporizing measures and different depths of
      sedation in an intensive care unit or high dependency unit are the most immediate
      and effective modalities for abating life-threatening spasms, while dystonia
      specific treatment takes effect. If refractory status dystonicus persists despite
      orally active anti-dystonia drugs and unsuccessful weaning from sedative or
      anaesthetic agents, early consideration of intrathecal baclofen or deep brain
      stimulation is required. During status dystonicus, precise documentation of
      dystonia sites and severity as well as the baseline clinical state, using rating
      scales and videos is recommended. Further published descriptions of the clinical
      nature, timing of evolution, resolution, and epidemiology of status dystonicus
      are essential for a better collective understanding of this poorly understood
      heterogeneous emergency. In this review, we provide an overview of the clinical
      presentation and suggest a management approach for status dystonicus. 

PMID- 24304391
TI  - Early treatment intensification with escalated BEACOPP in patients with Hodgkins
      lymphoma not responding to ABVD therapy.

PMID- 24304392
TI  - Chemotherapy as palliative treatment for peritoneal carcinomatosis of gastric
      origin.

PMID- 24304393
TI  - Influence of dose and duration of isoflurane anesthesia on the auditory brainstem
      response in the rat.
AB  - OBJECTIVE: Isoflurane anesthesia can have significant effects on processing of
      sounds at the peripheral and central levels, manifesting in changes in auditory
      evoked potentials. The current study tested whether duration of isoflurane
      anesthesia changes thresholds, amplitudes, and latencies of the auditory
      brainstem response (ABR). DESIGN: The study tested ABRs in a rat animal model
      under isoflurane anesthesia. Study variables were duration of isoflurane
      anesthesia, stimulus frequency, stimulus level, and the dose of isoflurane. Rats
      were anesthetized with 1.5% or 2% isoflurane. ABRs were collected from 90 to 5 dB
      SPL at 5-40 kHz. Three full ABR series were collected over a 105-minute period.
      Thresholds were assigned, and ABR wave amplitudes and latencies were measured at
      each stimulus frequency and level. STUDY SAMPLE: Ten Sprague-Dawley rats were
      tested in a repeated measures design. RESULTS: Statistical analyses revealed no
      significant effects of dose or duration on threshold, but a series of significant
      interactions between test variables for the amplitude and latency measurements.
      CONCLUSIONS: In the rat, dose and duration of isoflurane anesthesia induced
      inconsistent changes in latency and amplitude of the ABR. At 40 kHz, isoflurane
      dose had more powerful effects on latency and amplitude than occurred at other
      frequencies.

PMID- 24304394
TI  - Both associative activation and thematic extraction count, but thematic false
      memories are more easily rejected.
AB  - The main aim of this study was to analyse the roles played by associative
      activation and thematic extraction in the explanation of false memories using the
      Deese, Roediger, McDermott (DRM) paradigm. Associative lists with two different
      types of critical items (CIs) were used: one, the associative CI, corresponded to
      the word most strongly primed by the associates in the list and another, the
      thematic CI, was the word that best described the theme of the list. Following
      three different types of encoding instructions (standard, warning or strategic),
      false recognition for these two types of CIs was analysed in either self-paced or
      speeded response recognition tests. The results showed considerable levels of
      false memories for both types of CIs. Even without the quality of being "good
      themes", associative CIs produced high levels of false recognition, which
      suggests that associative activation plays a prominent role in false memory
      formation. More interestingly, thematic CIs were more prone to be edited out,
      reinforcing the argument that thematic identifiability has a major role in the
      rejection of false memories.

PMID- 24304395
TI  - AAEP/EVJ supplement 2013.

PMID- 24304396
TI  - Sequential L-lactate concentration in hospitalised equine neonates: A prospective
      multicentre study.
AB  - REASONS FOR PERFORMING STUDY: Evaluation of serial blood lactate concentrations
      [LAC] are of prognostic value for morbidity and mortality in critically ill human
      patients and neonatal foals, but have not been prospectively evaluated in a large
      multicentre study of critically ill neonatal foals. OBJECTIVES: To prospectively
      evaluate the prognostic value of sequential [LAC] analysis in critically ill
      neonatal foals with risk of mortality. STUDY DESIGN: Prospective, observational
      study. METHODS: Thirteen university and private equine referral hospitals
      enrolled 643 foals over the 2008 foaling season and [LAC] was measured at
      admission ([LAC]ADMIT ) and 24 ([LAC]24 ), 48 ([LAC]48 ), 72 ([LAC]72 ), 96
      ([LAC]96 ) and 120 h ([LAC]120 ) after admission. [LAC] changes over time
      ([LAC]Delta) were calculated between sampling points. RESULTS: Nonsurvivors had
      significantly greater [LAC]ADMIT , [LAC]24 and [LAC]48 compared with surviving
      foals (P<0.001). In nonsurviving foals [LAC]Delta did not decrease over time
      while survivors showed significant positive [LAC]Delta between [LAC]ADM -24 and
      all other time periods (P<0.001). Logistic regression analysis showed that the
      odds of survival decreased for each 1 mmol/l [LAC] increase at all time points
      for all critically ill foals, independent of major final diagnoses as potential
      confounders. Septic foals had significantly greater [LAC] at all time points
      compared with nonseptic foals (P<0.001) and [LAC]Delta in septic foals was
      significantly more positive (suggesting better clearance of lactate from the
      blood) only at [LAC]ADM -24 and [LAC]72-96 (P<0.01), while in nonseptic foals
      [LAC]Delta was significantly positive between [LAC]ADM -24 compared with all
      other time periods (P<0.001). CONCLUSIONS: Blood lactate concentration is a
      strong, independent biomarker used to predict mortality in critically ill foals.
      Lactate metabolism is impaired in nonsurviving and septic foals and [LAC]Delta
      can be utilised to identify patients at high risk for mortality.

PMID- 24304397
TI  - Risk factors associated with gastrointestinal dysfunction in horses undergoing
      elective procedures under general anaesthesia.
AB  - REASONS FOR PERFORMING STUDY: Gastrointestinal dysfunction occurs commonly
      following elective anaesthesia. Identification of risk factors may allow
      implementation of preventative measures to reduce the prevalence of colic
      following elective anaesthetic procedures. OBJECTIVES: To examine risk factors
      associated with gastrointestinal dysfunction or post anaesthetic colic for horses
      undergoing elective surgical or diagnostic procedures under general anaesthesia.
      STUDY DESIGN: Retrospective case series. METHODS: Medical records were collected
      from adult horses undergoing general anaesthesia from 1 January 2008 to 31
      December 2010 using a retrospective cohort design. Potential risk factors were
      examined using univariable logistic regression with a limit of a P<0.25. Through
      backward elimination, the final multivariate model was created to identify
      variables significantly associated with gastrointestinal dysfunction. RESULTS:
      Colic or delayed faecal output was reported in 36 out of 416 (8.7%) horses
      undergoing general anaesthesia in the study period. In the final multivariable
      model, horse breed (P = 0.05), intraoperative peripheral blood lactate (P =
      0.02), right lateral recumbency during general anaesthesia (P = 0.04), post
      anaesthetic rectal temperature (P = 0.03) and hours to first passage of faeces
      (P<0.01) were statistically significant between horses that exhibited colic
      compared with those that did not. Arabians were more likely to develop colic
      compared with other horse breeds (4/13, 30.8%). Horses that exhibited
      gastrointestinal dysfunction passed faeces later than those that did not (7.2 +/-
      0.8 h and 5.4 +/- 0.2 h, respectively). As blood lactate increased at the end of
      anaesthesia, the odds of colic occurring also increased (odds ratio:1.4, 95%
      confidence interval: 1.04-1.83, P = 0.02). CONCLUSIONS: This study demonstrated
      the prevalence of colic in horses undergoing elective general anaesthetic
      procedures in our hospital population. Arabian horses, increasing blood lactate
      and delayed passage of faeces were significantly associated with an increased
      risk of gastrointestinal dysfunction.

PMID- 24304398
TI  - Comparison of transverse facial venous sinus and jugular blood values in healthy
      and critically ill horses.
AB  - REASONS FOR PERFORMING STUDY: The transverse facial venous sinus (TFVS) can be
      used for blood collection in horses, but information on the validity of blood
      values from this site is limited. OBJECTIVES: To determine if packed cell volume
      (PCV), total solids (TS) and blood lactate concentrations in blood drawn
      simultaneously from a TFVS and jugular vein of critically ill horses are
      correlated and determine the effect of serial TFVS sampling on the same
      parameters in healthy horses. STUDY DESIGN: Prospective observational study.
      METHODS: Critically ill horses had simultaneous blood samples drawn from a TFVS
      and jugular vein. Blood was also drawn from the left TFVS and jugular vein from 6
      healthy, adult horses q. 6 h for 24 h, then q. 24 h for 72 h. Blood was drawn
      from the right TFVS and jugular vein q. 24 h for 96 h. All samples were analysed
      for PCV, TS and blood lactate concentration. Data were analysed with 2-way
      repeated measures ANOVA. Significance was set at P<=0.05. RESULTS: There were no
      significant differences in PCV, TS or blood lactate concentrations of TFVS
      samples compared with jugular blood in critically ill horses. Serial TFVS
      sampling in healthy horses had no significant effect on TS or blood lactate
      concentrations. Although PCV in the TFVS was significantly lower than in jugular
      blood on serial sampling, the difference was not considered clinically relevant.
      CONCLUSIONS: Packed cell volume, TS and blood lactate concentrations were
      comparable between the TFVS and jugular vein.

PMID- 24304399
TI  - Systemic and respiratory oxidative stress in the pathogenesis and diagnosis of
      Rhodococcus equi pneumonia.
AB  - REASONS FOR PERFORMING STUDY: Oxidative stress (OS) is most simply defined as an
      imbalance between oxidants and antioxidants. Oxidative stress has been suggested
      to play roles in various equine respiratory diseases and the significance of OS
      in the pathogenesis of Rhodococcus equi pneumonia is unknown. OBJECTIVES: To
      measure and relate biomarkers of OS to lesions consistent with R. equi pneumonia.
      STUDY DESIGN: Case-control study. METHODS: Various OS biomarkers were measured
      from blood and exhaled breath condensate (EBC) samples collected from 26 foals
      between 1 and 2 months of age (n = 12 cases and n = 14 controls) on 2
      Thoroughbred farms endemically affected by R. equi pneumonia. Foals were defined
      as cases (positive) or controls (negative) based on ultrasonographic evidence of
      pulmonary abscessation (>15 mm in diameter). Haematology and biochemistry testing
      was also performed on blood samples collected from the foals. Comparison of
      biomarkers and key haematological and biochemical markers of inflammation between
      the groups was performed using 2 sample t tests. RESULTS: Derivatives of reactive
      oxygen metabolites (d-ROMs) were significantly greater in case foals than in
      control foals (P = 0.027) and the oxidative stress index (OSI) was higher in case
      foals (P = 0.014). Hydrogen peroxide (H2 O2 ) concentrations in EBC were
      significantly greater in case foals than in control foals (P = 0.002). Meanwhile,
      there were no significant differences in traditional measures of inflammation
      between the 2 groups. CONCLUSIONS: Measuring OS in both blood and EBC provided
      useful information in the early diagnosis of R. equi pneumonia.

PMID- 24304400
TI  - An inertial sensor-based system can objectively assess diagnostic anaesthesia of
      the equine foot.
AB  - REASONS FOR PERFORMING STUDY: In order for changes in lameness to be accurately
      and repeatably detected and recorded during diagnostic investigations, an
      objective measure of lameness is required. OBJECTIVES: To ascertain whether an
      inertial sensor-based system can distinguish between a positive and negative
      response to diagnostic anaesthesia of the foot and objectively assess the effect
      of a positive response on the trot. STUDY DESIGN: Restrospective clinical study.
      METHODS: Data obtained during lameness investigations undertaken between August
      2011 and December 2012 in which either a palmar digital or abaxial sesamoid nerve
      block was performed were retrospectively reviewed. Response to diagnostic
      anaesthesia was categorised as positive (n = 14) or negative (n = 9) by one of 2
      evaluators before analysis of kinematic data (i.e. blinded). Changes in maximum
      and minimum head difference (DeltaHDMax and DeltaHDMin) and change in head
      movement asymmetry/change in pelvic movement asymmetry (DeltaHMA/PMA, measure of
      asymmetry) allocated to each limb were calculated. A Kruskal-Wallis one way
      analysis of variance on ranks was performed. Receiver operating characteristic
      (ROC) curves were generated for DeltaHDMax, DeltaHDMin and DeltaHMA for the
      blocked limb to identify cut-off values to distinguish positive and negative
      responses to the block. RESULTS: Median DeltaHDMax and DeltaHDMin were
      significantly greater after a positive response to diagnostic anaesthesia
      (P<0.01). Change in head movement asymmetry allocated to the blocked limb and
      contralateral forelimb and DeltaPMA allocated to the contralateral hindlimb were
      significantly greater in the positive response group (P<0.05). Change in head
      movement asymmetry allocated to the blocked limb and DeltaHDMax and DeltaHDMin
      are useful diagnostic tests for identifying positive response to anaesthesia
      (area under the curve = 0.98, 0.83 and 0.96 respectively). CONCLUSIONS: An
      inertial sensor-based system can identify a positive response to diagnostic
      anaesthesia of the foot. Symmetry of movement allocated to the blocked limb,
      contralateral forelimb and contralateral hindlimb significantly improve, and head
      movement significantly decreases in horses with a positive response to the block.
      Cut-off values for a positive response have been identified with good sensitivity
      and specificity. Forelimb lameness significantly affects contralateral hindlimb
      movement, which has implications for the investigation of multi-limb lameness.

PMID- 24304401
TI  - Ureteropyeloscopic anatomy of the renal pelvis of the horse.
AB  - REASONS FOR PERFORMING STUDY: Although the equine renal pelvis and terminal
      recesses have been described post mortem, little information exists about the
      endoscopic appearance of these structures in the living horse for guiding
      ureteropyeloscopy. OBJECTIVES: To further document the anatomy of the upper
      urinary collecting system, specifically the renal pelvis and terminal recesses,
      of the horse. STUDY DESIGN: Descriptive study of cadaver material. METHODS:
      Kidneys were harvested from 10 horses. Magnetic resonance imaging was performed
      after distension of the renal pelvis with an elastomer casting material, followed
      by visual inspection of corrosion casts. Transurethral ureteropyeloscopy of the
      upper urinary tract was performed in 4 horses, followed by histological and
      immunohistochemical examination of the renal medulla and pelvis of 3 animals.
      RESULTS: The equine renal pelvis was confirmed to be a funnel-shaped cavity,
      flattened dorsoventrally in the craniocaudal direction. Multiple papillary ducts
      (PDs) from the central part of the kidney open along a ~3 cm long renal crest
      that protrudes into the renal pelvis, while PDs from each kidney pole open into 2
      long (5-10 cm), narrow terminal recesses that terminate near either end of the
      renal crest. Openings of the terminal recesses narrow at their junction with the
      renal pelvis and could be visualised during ureteropyeloscopy in all horses.
      Minor anatomical variation of the renal crest and terminal recess openings was
      observed. CONCLUSIONS: Current endoscopic equipment can be used to visualise the
      renal pelvis but could not be advanced into the terminal recesses. The findings
      of this study will help guide future diagnostic and therapeutic
      ureteropyeloscopy.

PMID- 24304402
TI  - Effect of potential oocyte transport protocols on blastocyst rates after
      intracytoplasmic sperm injection in the horse.
AB  - REASONS FOR PERFORMING STUDY: Intracytoplasmic sperm injection (ICSI) is used to
      produce foals from otherwise infertile mares and from stallions with limited
      sperm stores, but requires expensive equipment and is technically demanding.
      Methods to transport oocytes to ICSI laboratories would allow collection of
      oocytes by the referring veterinarian and enable greater application of this
      technique. OBJECTIVES: This study was conducted to evaluate protocols that could
      be used to transport immature and maturing oocytes for ICSI. STUDY DESIGN: In
      vitro experiment. METHODS: Oocytes were recovered by transvaginal ultrasound
      guided follicular aspiration either from dominant follicles 24 h after deslorelin
      administration (dominant stimulated follicle [DSF]), or from subordinate
      (immature) follicles at the same time. To mimic transport, DSF oocytes were
      incubated overnight under differing conditions before ICSI; immature oocytes were
      placed in varying conditions overnight before in vitro maturation, followed by
      ICSI. The rate of blastocyst production was compared among treatments. RESULTS:
      Blastocysts were produced in all groups. Dominant stimulated follicle oocytes
      held in sealed tubes in pre-equilibrated control maturation medium maintained at
      37 degrees C yielded blastocyst development equal to that obtained for control
      incubated oocytes (70%). Dominant stimulated follicle oocytes held similarly in a
      warm passive device yielded poor blastocyst development (10%). Immature oocytes
      held for one or 2 nights in modified M199 medium, or for one night in commercial
      embryo holding solution, in air at room temperature, yielded 35-37% blastocyst
      development per injected oocyte. CONCLUSIONS: A commercially available medium can
      be used for shipping immature oocytes at room temperature with good resulting
      blastocyst rates. Better blastocyst rates per oocyte are obtained from DSF
      oocytes; however, these require maintenance at 37 degrees C and as they are
      already maturing at the time of collection, are more sensitive to delays. This
      new, practical information supporting transport of both immature and DSF oocytes
      for ICSI may allow wider use of this procedure.

PMID- 24304403
TI  - The effects of ergot alkaloids on the breeding stallion reproductive system.
AB  - REASONS FOR PERFORMING STUDY: Ergot alkaloids cause a range of pathological
      conditions in mares. There is no evaluation of the effects of ergot alkaloids
      from endophyte-infected tall fescue on the stallion breeding soundness
      examination spermiogram. OBJECTIVES: The objective of this study was to
      investigate the effect of ergot alkaloids from endophyte-infected tall fescue on
      the stallion's reproductive functions. STUDY DESIGN: Crossover toxicology
      experiment. METHODS: Six stallions were fed either toxic endophyte-infected tall
      fescue seed or a nontoxic endophyte tall fescue seed (Flecha AR-542, MaxQ). The
      fescue seed content was compounded at 45% of a grain diet and the stallions were
      fed the grain diet at 1% of their body weight. The stallions were fed the diet
      for 70 days, then rested for at least 70 days (no fescue seed) and then fed
      fescue seed for a second 70 days. At regular intervals blood sampling and a
      breeding soundness examination were performed. RESULTS: The mean time to maximal
      systemic toxicity was 8.33 h after starting toxic seed ingestion with a mean
      toxicity level of 49.98 ng alkaloid/mg creatinine. After cessation of feeding
      toxic seed, the systemic alkaloid concentration fell to control levels within 48
      h. There were no significant changes in sperm motility, sperm concentration,
      sperm cell morphology, total number of sperm cells, number of breeding doses,
      testicular volume, baseline and human chorionic gonadotropin stimulated
      testosterone levels. There were no changes in core body temperature and
      superficial scrotal temperature. The ejaculate from stallions consuming endophyte
      infected tall fescue seed had significantly lower gel-free volume (47.5 +/- 4.1
      ml) than stallions consuming nontoxic endophyte tall fescue seed (62.8 + 4.3 ml,
      P<0.01). CONCLUSION: Ergot alkaloids decreased the gel-free volume of stallions
      consuming high levels of ergot alkaloids but statistically significant effects on
      the spermiogram of adult breeding stallions were not found.

PMID- 24304404
TI  - Efficacy of intramuscular meperidine hydrochloride versus placebo in experimental
      foot lameness in horses.
AB  - REASONS FOR PERFORMING STUDY: There are no peer reviewed, blinded controlled
      studies regarding the skeletal analgesic efficacy of intramuscularly administered
      meperidine in horses. OBJECTIVES: Using an adjustable heart bar shoe model of
      equine foot pain, the objective of this study was to test the hypothesis that
      meperidine (pethidine) administered intramuscularly would prove more efficacious
      in alleviating lameness than a saline placebo. STUDY DESIGN: Crossover
      pharmacodynamic experiment. METHODS: Eight healthy adult Thoroughbred horses
      randomly underwent weekly i.m. treatments 1 h after lameness induction: saline
      placebo (1 ml/45 kg bwt) or meperidine hydrochloride (1 mg/kg bwt i.m.). Heart
      rate (HR) and lameness score (LS) responses were assessed by a blinded observer
      every 20 min for 5 h after lameness induction and then hourly through 12 h after
      treatment. Jugular venous blood samples were obtained at -1, 0, 0:05, 1, 2, 4, 6,
      8, 10 and 12 h and were subsequently analysed for drug concentrations (lower
      limit of detection, 1 ng/ml). Repeated measures ANOVA and post hoc Tukey's test
      were used to identify analgesic effects at a significance level of P<0.05.
      RESULTS: Mean (+/- s.e.) HR were lower in meperidine trials at 2.3, 3.3 and 3.7 h
      post administration (P<0.05). Mean LS were lower in meperidine trials at 2.0, 2.3
      and 3.3 h post administration (P<0.05). Mean plasma (meperidine) peaked at 227 +/
      52 ng/ml at 1 h post administration and decreased to 2.7 +/- 0.3 ng/ml at 12 h
      post administration. In 3 of 8 subjects, plasma (meperidine) was below the lower
      limit of detection at 12 h after administration. CONCLUSIONS: Intramuscular
      meperidine was more effective than the saline placebo but only for 2.0-3.7 h post
      administration compared with the 8-12 h durations of efficacy reported previously
      using this same model when horses were treated with nonsteroidal anti
      inflammatory drugs (NSAIDs). Meperidine may be a suitable nonNSAID alternative
      analgesic for acute foot pain with efficacy lasting from 2-3 h after a single
      i.m. dose.

PMID- 24304405
TI  - Comparative kinematic analysis of the leading and trailing forelimbs of horses
      cantering on a turf and a synthetic surface.
AB  - REASONS FOR PERFORMING STUDY: The relationship between track surface properties
      and limb kinematics is poorly understood. Hoof orientation within the track
      surface has never been quantified under training conditions. Previously described
      kinematic and dynamic differences between leading and trailing forelimbs at the
      canter poorly correlate with epidemiological data regarding injuries. OBJECTIVES:
      To compare joint kinematics and hoof orientation in the leading and trailing
      forelimbs of horses cantering on turf and on a synthetic surface. STUDY DESIGN:
      Noninvasive experimental study. METHODS: The right forelimb of 5 horses was
      equipped with markers facing the main joints while markers and a dynamometric
      horseshoe were placed on the hoof. The horses were filmed with 2 high-speed
      cameras (1000 Hz) while cantering (30 km/h). Recordings were repeated at each
      lead and alternated on turf and on a synthetic surface. Joint angles and angles
      of the hoof and limb to the track were measured from the 2-dimensional
      coordinates of the markers. RESULTS: Elbow, carpus and fetlock were more
      maximally flexed during swing and had a larger range of motion throughout the
      stride in the leading forelimb. Maximal carpal extension during stance was also
      larger on this limb, which had a more toe-up orientation. Comparing surfaces, the
      limb was more oblique at landing, the range of motion of the hoof into the
      surface was larger, most kinematic events were delayed and fetlock and carpus
      extension velocities were smaller on the synthetic surface. CONCLUSIONS: The
      differences between limbs were more prominent than those between surfaces and the
      more toe-up orientation on the hoof of the leading forelimb suggests a different
      loading of that limb's joints and tendons. Differences between limbs may be
      important in the interpretation of lead changes in lame horses. While the
      synthetic surface appears to be less strenuous for the joints in the forelimbs,
      it was associated with changes in timing of the kinematic events of the stride.

PMID- 24304406
TI  - Peroral endoscopic myotomy for achalasia.
AB  - BACKGROUND: Treatment of achalasia is complicated by symptom recurrence and a
      significant risk for severe complications. Endoscopic myotomy was developed in
      the search for a highly efficacious treatment with lower risks. Since its
      introduction in 2010, several centers have adopted the technique and published
      excellent short-term results of open label series. Randomized trials with long
      term endpoint comparing per-oral endoscopic myotomy (POEM) with the established
      treatments such as balloon dilation and surgical myotomy are now warranted,
      before POEM can be regarded as the routine clinical care for achalasia patients.
      PURPOSE: This review describes the development, technical aspects, efficacy, and
      complications of POEM.

PMID- 24304407
TI  - Day-night contrast as source of health for the human circadian system.
AB  - Modern societies are characterized by a 24/7 lifestyle (LS) with no environmental
      differences between day and night, resulting in weak zeitgebers (weak day light,
      absence of darkness during night, constant environmental temperature, sedentary
      LS and frequent snacking), and as a consequence, in an impaired circadian system
      (CS) through a process known as chronodisruption. Both weak zeitgebers and CS
      impairment are related to human pathologies (certain cancers, metabolic syndrome
      and affective and cognitive disorders), but little is known about how to
      chronoenhance the CS. The aim of this work is to propose practical strategies for
      chronoenhancement, based on accentuating the day/night contrast. For this, 131
      young subjects were recruited, and their wrist temperature (WT), activity, body
      position, light exposure, environmental temperature and sleep were recorded under
      free-living conditions for 1 week. Subjects with high contrast (HC) and low
      contrast (LC) for each variable were selected to analyze the HC effect in
      activity, body position, environmental temperature, light exposure and sleep
      would have on WT. We found that HC showed better rhythms than LC for every
      variable except sleep. Subjects with HC and LC for WT also demonstrated
      differences in LS, where HC subjects had a slightly advanced night phase onset
      and a general increase in day/night contrast. In addition, theoretical high
      day/night contrast calculated using mathematical models suggests an improvement
      by means of LS contrast. Finally, some individuals classified as belonging to the
      HC group in terms of WT when they are exposed to the LS characteristic of the LC
      group, while others exhibit WT arrhythmicity despite their good LS habits,
      revealing two different WT components: an exogenous component modified by LS and
      another endogenous component that is refractory to it. Therefore, intensifying
      day/night contrast in subject's LS has proven to be a feasible measure to
      chronoenhance the CS. 

PMID- 24304408
TI  - Comparison of 7 versus 14 days wrist actigraphy monitoring in a sleep disorders
      clinic population.
AB  - Wrist actigraphy is a valid measure to assess sleep and circadian rhythm
      abnormalities. It is listed in the diagnostic criteria for sleep disorders where
      single night polysomnography is insufficient (ICSD-2). However, an optimal
      recording time remains unclear. We hypothesised that seven days would provide
      sufficient data for analysis, similar to recordings for 14 days. We analysed
      three consecutive years of actigraphy data obtained within a tertiary sleep
      referral centre. Data were recorded continuously for two weeks using an AW4
      actiwatch (Cambridge NeuroTechnology, Cambridge, UK; Mini Mitter Co, Sunriver,
      OR). Parameters, including sleep efficiency (SE), sleep latency (SL), sleep
      fragmentation index (SFI), total sleep time (TST) and wake after sleep onset
      (WASO) were analysed using GraphPad Prism (Version 5.02, GraphPad Software Inc,
      San Diego, CA) and classified into week one, week two and an overall average for
      the duration of 14 days. In addition, two experienced consultants working in the
      sleep laboratory compared the results of week one versus week two independently,
      visually analysing the data for circadian rhythmicity and fragmentation of the
      pattern, allowing calculation of the intraclass correlation coefficient (ICC),
      kappa. The actigraphies of 239 patients (51.9% male; age 42 (16) years) were
      analysed. There was no difference in SE, SL, SFI or WASO between week one, week
      two and 14 days average recording. A small difference was found between TST week
      one (399.9 minutes, 95% CI 389.9-409.9 minutes) and TST week two (388.7 minutes,
      95% CI 378.3-399.1 minutes), but not between TST for 14 days average recording
      (394.3 minutes, 95% CI 384.7-403.9 minutes) and either week. Independent scorers
      achieved a good agreement in the rhythmicity of the sleep pattern (ICC kappa
      0.734, p < 0.001) and a low agreement for the fragmentation of the pattern (ICC
      kappa 0.380, p < 0.001). One week of wrist actigraphy recording provides similar
      data to two week actigraphies, despite subtle differences between the weeks. One
      week wrist actigraphy could be recommended as standard compared to longer
      recordings to maximise efficiency of the clinical service. Further studies are
      required to validate our results in specific clinical subgroups.

PMID- 24304409
TI  - Body weight gain in rats by a high-fat diet produces chronodisruption in
      activity/inactivity circadian rhythm.
AB  - In the last few decades, obesity has become one of the most important public
      health problems. Adipose tissue is an active endocrine tissue which follows a
      rhythmic pattern in its functions and may produce alterations in certain
      circadian rhythms. Our aim was to evaluate whether the locomotor activity
      circadian rhythm could be modified by a hypercaloric diet in rodents. Two groups
      were considered in the experiment: 16 rats were used as a control group and were
      fed standard chow; the other group comprised 16 rats fed a high-fat diet (35.8%
      fat, 35% glucides). The trial lasted 16 weeks. Body weight was measured every
      week, and a blood sample was extracted every two weeks to quantify triglyceride
      levels. The activity/inactivity circadian rhythm was logged through actimetry
      throughout the trial, and analysed using the DAS 24(c) software package. At the
      end of the experiment, the high-fat fed rats had obese-like body weights and high
      plasma triglyceride levels, and, compared with the control group, increased
      diurnal activity, decreased nocturnal activity, reductions in amplitude, midline
      estimating statistic of rhythm, acrophase and interdaily stability, and increases
      in intradaily variability of their activity rhythms. The results thus show how
      obesity can lead to symptoms of chronodisruption in the body similar to those of
      ageing. 

PMID- 24304410
TI  - Incisional hernia repair in horses: a cadaveric study of endoscopic component
      separation.
AB  - OBJECTIVE: To report a technique for endoscopic component separation in horses
      and quantify the amount of body wall advancement obtained. STUDY DESIGN:
      Descriptive study. ANIMALS: Fresh cadaveric horses (n = 14). METHODS: After a
      preliminary anatomic study, 7 horses had unilateral endoscopic component
      separation involving transection of the external abdominal oblique fascia lateral
      to the rectus abdominis muscle. A laparoscope, placed using a balloon dissector,
      was used to create an intermuscular working space between the external abdominal
      oblique fascia and internal abdominal oblique muscle. A single instrument portal
      was created 10-12 cm medial to the laparoscope portal. Laparoscopic scissors were
      used to transect the external abdominal oblique fascia, lateral to its insertion
      to the external rectus sheath, from ~ 20 cm cranial to the costochondral junction
      to the level of the superficial inguinal ring. Subsequently, a 30 cm ventral
      median celiotomy was created and the myofascial advancement was quantified at
      points 10 and 20 cm cranial to the umbilicus. RESULTS: Endoscopic component
      separation was successfully completed in all horses. Component separation
      provided a net mean (+/- SD) abdominal wall advancement of 3.5 +/- 1.3 cm and 3.4
      +/- 0.5 cm, 10 cm, and 20 cm cranial to the umbilicus, respectively. CONCLUSION:
      Endoscopic component separation in horses is technically feasible but, as
      conducted, results in modest abdominal wall advancement.

PMID- 24304411
TI  - Smoking in young adult African Americans.
AB  - AIM: The aim of this study was to describe factors that influence decisions of
      young African Americans to start smoking. BACKGROUND: Young adult African
      Americans have a high risk for becoming regular smokers, but little is understood
      about their smoking. This knowledge is needed because understanding young adults'
      smokers will help develop effective tobacco cessation and prevention strategies.
      DESIGN: Qualitative study. METHOD: The study consisted of 22 in-depth interviews
      with African Americans between the ages of 19-25. Data were collected between
      2009-2010. Smokers, former smokers and non-smokers were included.
      RESULTS/FINDINGS: Results indicated that smoking identity of young adults was
      influenced by their limited and discounted knowledge of health risks and the
      stigma associated with the type of tobacco smoked. The importance of cost was
      discussed as was the effect of smoking on relationships and vice versa. Marijuana
      was the primary reason they started smoking tobacco. Their transition into
      adulthood and views of smoking, adulthood and success all influenced smoking.
      Additionally, self-reflection on personal choices around smoking was important
      and may be useful in effective smoking cessation programmes for this group.
      CONCLUSION: Nurses are in an ideal position to promote effective smoking
      cessation in young adults. Direct, culturally relevant messages are needed that
      fit into the context of the young adults' lives by addressing concurrent use of
      marijuana, self-esteem and success in life.

PMID- 24304412
TI  - Maintenance treatment for opioid dependence with slow-release oral morphine: a
      randomized cross-over, non-inferiority study versus methadone.
AB  - AIMS: To compare the efficacy of slow-release oral morphine (SROM) and methadone
      as maintenance medication for opioid dependence in patients previously treated
      with methadone. DESIGN: Prospective, multiple-dose, open label, randomized, non
      inferiority, cross-over study over two 11-week periods. Methadone treatment was
      switched to SROM with flexible dosing and vice versa according to period and
      sequence of treatment. SETTING: Fourteen out-patient addiction treatment centres
      in Switzerland and Germany. PARTICIPANTS: Adults with opioid dependence in
      methadone maintenance programmes (dose >=50 mg/day) for >=26 weeks. MEASUREMENTS:
      The efficacy end-point was the proportion of heroin-positive urine samples per
      patient and period of treatment. Each week, two urine samples were collected,
      randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non
      inferiority was concluded if the two-sided 95% confidence interval (CI) in the
      difference of proportions of positive urine samples was below the predefined
      boundary of 10%. FINDINGS: One hundred and fifty-seven patients fulfilled
      criteria to form the per protocol population. The proportion of heroin-positive
      urine samples under SROM treatment (0.20) was non-inferior to the proportion
      under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI =
      0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin,
      confirming the non-inferiority of SROM to methadone. A dose-dependent effect was
      shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with
      increasing SROM doses). Retention in treatment showed no significant differences
      between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%;
      period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar
      between the two groups. CONCLUSIONS: Slow-release oral morphine appears to be at
      least as effective as methadone in treating people with opioid use disorder.

PMID- 24304413
TI  - Prolactin induces the production of Th17 and Th1 cytokines/chemokines in murine
      Imiquimod-induced psoriasiform skin.
AB  - BACKGROUND: Prolactin (PRL) is a pituitary-derived neuropeptide hormone that has
      been suggested to promote the development of psoriasis, a Th17/Th1-mediated
      inflammatory dermatosis. PRL increases the expression of Th1 cytokines; however,
      its effects on Th17 responses are unknown. OBJECTIVE: This study aims to
      determine the in vivo effects of PRL on the expression of Th17
      cytokines/chemokines in imiquimod-induced psoriasiform skin inflammation in mice.
      METHODS: BALB/c mice were intraperitoneally injected with PRL or phosphate
      buffered saline, and imiquimod cream or Vaseline was applied to the shaved back
      skin for six consecutive days. RESULTS: Intraperitoneal PRL increased the mRNA
      levels of IL-17A, IL-17F, IL-22, IL-23p19, IL-12p40, CCL20 and STAT3 in imiquimod
      treated skin. Mice treated with imiquimod plus PRL, but not those treated with
      imiquimod plus phosphate-buffered saline, showed significantly increased mRNA
      levels of TNF-alpha, IFN-gamma, IL-12p35 and CXCL2 compared with controls.
      Intraperitoneal PRL increased the numbers of CD3(+) and GR-1(+) cells in the
      dermis of imiquimod-treated skin. CONCLUSIONS: These results suggest that
      intraperitoneal PRL enhances the expression of Th17 and Th1 cytokines/chemokines,
      and augments inflammation in imiquimod-induced psoriasiform skin. Prolactin may
      thus exacerbate psoriasis through the enhancement of Th17/Th1 responses.

PMID- 24304414
TI  - Elasticity properties of pulmonary artery in patients with bicuspid aortic valve.
AB  - OBJECTIVE: Although the vascular complications of bicuspid aortic valve (BAV)
      disease cause significant morbidity and mortality, the role of pulmonary artery
      in this pathogenesis is less understood. We aimed to assess the elastic
      properties of pulmonary artery with echocardiography in patients with BAV.
      MATERIAL AND METHODS: Thirty patients with BAV (26 males) were enrolled in this
      study. The presence of aortic stenosis was accepted as exclusion criteria. Thirty
      two healthy subjects (27 males) with no any history of cardiovascular disease
      comprised the control group. In all patients, maximal frequency shift (MFS) and
      acceleration time (AcT) of the pulmonary artery flow trace were measured
      echocardiographically in parasternal short-axis view. Subsequently, pulmonary
      artery stiffness (PAS) was calculated by using the following formula PAS
      (kHz/sec) = MFS/AcT. RESULTS: There were no significant differences in baseline
      demographic characteristics of the study population. Aortic strain and aortic
      distensibility index were lower, and aortic stiffness index (SI) higher, in
      patients with BAV. The PAS was significantly increased in patients with BAV
      compared with control subjects with tricuspid aortic valve (11.08 +/- 2.27 vs.
      7.11 +/- 1.54, P < 0.001). There was a significant correlation between aortic
      diameters, aortic elasticity indexes, and PAS. Multivariate linear regression
      analysis, the only significant independent factor affecting the PAS was SI (beta
      = 0.547, P < 0.001). CONCLUSION: We demonstrated that elastic properties of
      pulmonary artery tend to be impaired as in the aorta in patients with BAV
      disease.

PMID- 24304415
TI  - Molecular markers and targeted therapies for adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a lethal disease with poor prognosis and lack
      of effective therapeutic options. Systemic treatment is often employed to treat
      patients with advanced ACC, but outcomes are disappointing. During the last
      decade, some of the causative genetic mutations in sporadic ACCs have been
      identified. Molecular analysis has had a significant impact on the understanding
      of the pathogenetic mechanism of ACC development and the evaluation of prognostic
      and predictive markers. Preclinical investigations and clinical trials of
      tyrosine kinase inhibitors and anti-angiogenic compounds have been initiated to
      seek target therapy of ACCs. This review summarizes the current view of molecular
      alterations involved in the pathophysiology of adrenocortical carcinogenesis. The
      rationale for testing targeted therapies of ACC is also presented. 

PMID- 24304416
TI  - Heterometallic triiron-oxo/hydroxo clusters: effect of redox-inactive metals.
AB  - A series of tetranuclear oxo/hydroxo clusters comprised of three Fe centers and a
      redox-inactive metal (M) of various charge is reported. Crystallographic studies
      show an unprecedented Fe3M(MU4-O)(MU2-OH) core that remains intact upon changing
      M or the oxidation state of iron. Electrochemical studies reveal that the
      reduction potentials (E1/2) span a window of 500 mV and depend upon the Lewis
      acidity of M. Using the pKa of the M-aqua complex as a measure of Lewis acidity,
      these compounds display a linear dependence between E1/2 and acidity, with a
      slope of ~70 mV per pKa unit. The current study of [Fe3MO(OH)] and previous ones
      of [Mn3MOn] (n = 2,4) moieties support the generality of the above relationship
      between the reduction potentials of heterometallic oxido clusters and the Lewis
      acidity of incorporated cations, as applied to clusters of different redox-active
      metals. 

PMID- 24304417
TI  - Nitrene-carbene-carbene rearrangement. Photolysis and thermolysis of
      tetrazolo[5,1-a]phthalazine with formation of 1-phthalazinylnitrene, o
      cyanophenylcarbene, and phenylcyanocarbene.
AB  - 1-Azidophthalazine 9A is generated in trace amount by mild FVT of tetrazolo[5,1
      a]phthalazine 9T and is observable by its absorption at 2121 cm(-1) in the Ar
      matrix IR spectrum. Ar matrix photolysis of 9T/9A at 254 nm causes ring opening
      to generate two conformers of (o-cyanophenyl)diazomethane 11 (2079 and 2075 cm(
      1)), followed by (o-cyanophenyl)carbene (3)12, cyanocycloheptatetraene 13, and
      finally cyano(phenyl)carbene (3)14 as evaluated by IR spectroscopy. The two
      carbenes (3)12 and (3)14 were observed by ESR spectroscopy (D|hc = 0.5078, E|hc =
      0.0236 and D|hc = 0.6488, E|hc = 0.0195 cm(-1), respectively). The rearrangement
      of 12 ? 13 ? 14 constitutes a carbene-carbene rearrangement. 1
      Phthalazinylnitrene (3)10 is observed by means of its UV-vis spectrum in Ar
      matrix following FVT of 9 above 550  degrees C. Rearrangement to
      cyanophenylcarbenes also takes place on FVT of 9 as evidenced by observation of
      the products of ring contraction, viz., fulvenallenes and ethynylcyclopentadienes
      16-18. Thus the overall rearrangement 10 -> 11 -> 12 ? 13 ? 14 can be formulated.

PMID- 24304418
TI  - Association of XRCC3 Thr241Met polymorphism and leukemia risk: evidence from a
      meta-analysis.
AB  - The relationship between the X-ray repair cross-complementing group 3 (XRCC3)
      Thr241Met (rs861539) polymorphism and the risk of leukemia remains inclusive or
      controversial. For a better understanding of the effect of XRCC3 Thr241Met
      (rs861539) polymorphism on leukemia risk, we performed a meta-analysis. All
      eligible studies were identified through a search of PubMed, Excerpta Medica
      Database (Embase) and the Chinese Biomedical Literature Database (CBM) up to
      August 2013. The association between the XRCC3 Thr241Met (rs861539) polymorphism
      and leukemia risk was analyzed by means of odds ratios (ORs) and 95% confidence
      intervals (CI). Ultimately, seven studies with 1070 cases and 1850 controls were
      included in the meta-analysis. There was no association between Thr241Met
      polymorphism and leukemia risk in any of the five models in the overall
      populations (T vs. C: OR = 1.43, 95% CI = 0.95-2.13, p = 0.086; TT vs. CC: OR =
      1.71, 95% CI = 0.88-3.33, p = 0.112; TC vs. CC: OR = 1.35, 95% CI = 0.96-1.91, p
      = 0.089; TT vs. TC/CC: OR = 1.59, 95% CI = 0.87-2.89, p = 0.132; TT/TC vs. CC: OR
      = 1.37, 95% CI = 0.98-1.94, p = 0.070). In subgroup analysis according to
      ethnicity, a significant association was found between XRCC3 Thr241Met (rs861539)
      polymorphism and leukemia risk in Asian but not in Caucasian or mixed
      populations. In conclusion, the results suggest no association between XRCC3
      Thr241Met (rs861539) polymorphism and leukemia risk in the overall populations
      but a significant association between XRCC3 Thr241Met (rs861539) polymorphism and
      leukemia risk in the Asian population. Considering the limited sample size and
      ethnicities included in the meta-analysis, further large-scale, well-designed
      studies are needed to confirm our results.

PMID- 24304419
TI  - Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody
      obinutuzumab (GA101) in combination with chemotherapy in xenograft models of
      human lymphoma.
AB  - Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in
      development for non-Hodgkin lymphoma. We compared the anti-tumor activity of
      obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU
      DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and
      in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and
      cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these
      models, suboptimal doses of obinutuzumab were applied to demonstrate a
      combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth
      inhibition versus rituximab plus bendamustine and showed a statistically
      significant effect versus the respective single treatments. Combinations of
      obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine
      demonstrated significantly superior activity to rituximab-based treatment.
      Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy
      in vivo, and obinutuzumab plus chemotherapy was superior to the respective
      monotherapies. These data support further clinical investigation of obinutuzumab
      plus chemotherapy.

PMID- 24304420
TI  - Potential new risks of lenalidomide.

PMID- 24304421
TI  - Prospective analysis of low-level BCR-ABL1 T315I mutation in CD34 + cells of
      patients with de novo chronic myeloid leukemia.

PMID- 24304422
TI  - Solid-phase synthesis of 5-noranagrelide derivatives.
AB  - Solid-phase synthesis of 1H-benzo[d]imidazo[1,2-a]imidazol-2(3H)-one derivatives
      employing Fmoc-alpha-amino acids and nitroaryl fluorides as key building blocks
      has been developed. The Fmoc-alpha-amino acids immobilized on Wang resin,
      equipped with a piperazine carbamate linker, were transformed to o-nitroanilines
      in two steps. After reduction of the nitro group, the corresponding o
      phenylenediamines gave the 2-aminobenzimidazole scaffold by reaction either with
      cyanogen bromide or with Fmoc-NCS. Cleavage from the polymer support and further
      cyclization afforded the target compounds. The developed methodology represents a
      versatile and simple approach for the preparation of various corresponding 1H
      benzo[d]imidazo[1,2-a]imidazol-2(3H)-ones from a large number of commercially
      available building blocks. 

PMID- 24304423
TI  - Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal
      imaging.
AB  - Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have
      been prepared. The bis(aqua)gadolinium(III) complex Gd.L1 and
      mono(aqua)gadolinium(III) complex Gd.L2 behave as dual-modal imaging probes (r1 =
      8.5 and 3.8 mM(-1) s(-1) for Gd.L1 and Gd.L2, respectively; lambdaex = 560 nm and
      lambdaem = 580 nm for both complexes). The rhodamine fragment is pH-sensitive,
      and upon lowering of the pH, an increase in fluorescence intensity is observed as
      the spirolactam ring opens to give the highly fluorescent form of the molecule.
      The ligands are bimodal when coordinated to Tb(III) ions, inducing fluorescence
      from both the lanthanide center and the rhodamine fluorophore, on two independent
      time frames. Confocal imaging experiments were carried out to establish the
      localization of Gd.L2 in HEK293 cells and primary mouse islet cells (~70% insulin
      containing beta cells). Colocalization with MitoTracker Green demonstrated
      Gd.L2's ability to distinguish between tumor and healthy cells, with
      compartmentalization believed to be in the mitochondria. Gd.L2 was also evaluated
      as an MRI probe for imaging of tumors in BALB/c nude mice bearing M21 xenografts.
      A 36.5% decrease in T1 within the tumor was observed 30 min post injection,
      showing that Gd.L2 is preferentially up taken in the tumor. Gd.L2 is the first
      small-molecule MR/fluorescent dual-modal imaging agent to display an off-on pH
      switch upon its preferential uptake within the more acidic microenvironment of
      tumor cells. 

PMID- 24304425
TI  - Nature of child sexual abuse and psychopathology in adult survivors: results from
      a clinical sample in Scotland.
AB  - The relationship between history of childhood sexual abuse and psychopathology in
      adult life is well established. However, understanding of the mechanisms by which
      abuse exerts its effects is limited. To our knowledge, this is the first study
      which investigates the relationship between a wide range of sexual abuse
      characteristics (i.e. age at onset, frequency of assaults, number of perpetrators
      and their relationship to the victim) and the severity of psychopathological
      disorders in a large sample of adult child sexual abuse (CSA) survivors who
      attended a specialist Psychotherapy Service for CSA survivors. CSA survivors in
      our study experienced severe sexual assault(s) in their early years and presented
      with severe pathology which could suggest a strong causal link. However, none of
      the examined trauma characteristics significantly predicted severity of
      psychopathology. This may suggest that for severely disordered, treatment-seeking
      CSA survivors post-abuse psychopathology could be caused by other factors. The
      study adds to the growing body of evidence suggesting that CSA effects may be
      dependent on factors which are not necessarily related to the nature of sexual
      abuse. The study findings will help improve clinicians' insight into the
      determinants of psychopathology.

PMID- 24304424
TI  - Novel pyridazinone inhibitors for vascular adhesion protein-1 (VAP-1): old target
      new inhibition mode.
AB  - Vascular adhesion protein-1 (VAP-1) is a primary amine oxidase and a drug target
      for inflammatory and vascular diseases. Despite extensive attempts to develop
      potent, specific, and reversible inhibitors of its enzyme activity, the task has
      proven challenging. Here we report the synthesis, inhibitory activity, and
      molecular binding mode of novel pyridazinone inhibitors, which show specificity
      for VAP-1 over monoamine and diamine oxidases. The crystal structures of three
      inhibitor-VAP-1 complexes show that these compounds bind reversibly into a unique
      binding site in the active site channel. Although they are good inhibitors of
      human VAP-1, they do not inhibit rodent VAP-1 well. To investigate this further,
      we used homology modeling and structural comparison to identify amino acid
      differences, which explain the species-specific binding properties. Our results
      prove the potency and specificity of these new inhibitors, and the detailed
      characterization of their binding mode is of importance for further development
      of VAP-1 inhibitors.

PMID- 24304426
TI  - A survey of zeb1, twist and claudin 1 and 4 expression during placental
      development and disease.
AB  - We investigated zeb1, twist and claudins 1 and 4 in normal and diseased placental
      tissues. Eighty cases of placental tissues from all three trimesters and from
      different diseases were studied immunohistochemically to determine the expression
      of zeb1, twist and claudins 1 and 4. Zeb1 was more strongly expressed in
      endothelial and mesenchymal cells of the villous structures during the last two
      trimesters, suggesting that it plays a role in the development of placental blood
      vessels. In contrast, twist was more strongly expressed in the trophoblastic
      cells during these trimesters. The endothelial and stromal expression of zeb1 and
      the epithelial expression of twist were disturbed in those placentas with
      chromosomal aberrations. Claudin 4 was strongly expressed in trophoblastic cells
      during all trimesters. Its expression was especially strong in molar disease,
      suggesting that it could participate in trophoblastic aggregation and disturbed
      attachment of trophoblastic cells in the expanded villi. Claudin 4 expression was
      also increased in the placentas of diabetic mothers and in toxaemia. Claudin 1
      did not show any specific disease associations. The study implicates that twist
      and zeb1 are involved in placental maturation, whereas claudin 4 appears to be
      connected with placental diseases such as diabetes, toxaemia or molar disease. 

PMID- 24304427
TI  - Mass spectrometry methods for studying structure and dynamics of biological
      macromolecules.

PMID- 24304428
TI  - Risk for tuberculosis in child contacts. Development and validation of a
      predictive score.
AB  - RATIONALE: Contact investigation of persons exposed to tuberculosis (TB) is
      resource intensive. To date, no clinical prediction rule for TB risk exists for
      use as a guide during contact investigation. OBJECTIVES: We sought to develop and
      validate a simple and easy-to-use predictive score for TB risk, using data
      routinely available during contact investigation. METHODS: The derivation cohort
      consisted of 9,411 children aged 0 to 12 years from 2008 to 2009 national
      contacts cohort. We used a multivariate Cox proportional hazards model to predict
      the risk of developing active TB. The validation cohort consisted of 2,405
      children from the 2005 national contacts cohort. We calculated area under the
      receiver operating characteristic curves of the model as well as the predicted
      risk of TB for contacts with different scores. MEASUREMENTS AND MAIN RESULTS: An
      8-point scoring system was developed, including reaction to tuberculin skin test
      of the contacts, as well as smear-positivity, residence in high-incidence areas,
      and sex of the index cases. Area under the receiver operating characteristic
      curve was 0.872 (95% confidence interval, 0.810-0.935) for the derivation cohort
      and 0.900 (95% confidence interval, 0.830-0.969) for the validation cohort. The
      risk of developing active TB within 3 years is 100, 7.8, 4.3, 1.0, 0.7, and 0.2%
      for contacts with risk scores of 7, 6, 5, 4, 3, and 2, respectively. CONCLUSIONS:
      A risk predictive score was developed and validated to identify child contacts
      aged 0 to 12 years at increased risk for active TB. This predictive score can
      help to prioritize active case finding or isoniazid preventive therapy among
      children exposed to TB.

PMID- 24304429
TI  - A retrospective analysis of the risk factors for allergic reactions induced by
      the administration of oxaliplatin.
AB  - This study retrospectively investigated the clinical features and risk factors of
      allergic reactions induced by oxaliplatin administration. This study investigated
      the incidence of allergic reactions and analysed the background and laboratory
      data in patients with colorectal cancer treated with oxaliplatin-based
      chemotherapy at Kyushu Medical Center between April 2012 and September 2012. A
      total of 62 patients were included in this study. The number of patients in the
      allergic and non-allergic groups was 7 and 55 respectively. The incidence of
      allergic reactions was 11.3%. We compared the patients' characteristics and
      laboratory data between the two groups and found that the average dose of
      dexamethasone in the allergic group was significantly lower than that observed in
      the non-allergic group (P = 0.0111). Furthermore, the incidence of allergic
      reactions in the group that received prophylaxis of less than 12 mg of
      dexamethasone was significantly higher than that observed in the group that
      received more than 12 mg of dexamethasone (P = 0.0103). In conclusion, a lower
      dexamethasone dose is a possible risk factor for allergic reactions induced by
      the administration of oxaliplatin; however, given the retrospective design used
      in this study, further validation of this finding is warranted. 

PMID- 24304430
TI  - Modeling potential effects of reduced calories in kids' meals with toy giveaways.
AB  - BACKGROUND: Given the large proportion of daily calories attributable to fast
      food, there is growing interest in considering whether ordinances that restrict
      calories in kids' meals with toy giveaways could avert weight gain among
      children. METHODS: Based upon a literature review and stakeholder feedback, a
      model was developed to estimate the potential number of children that could be
      affected by a statewide toy giveaway ordinance and the caloric savings should
      such a policy effectively reduce the number of calories in kids' meals with toy
      giveaways. Assumptions included the estimated number of children that eat fast
      food each day, the proportion that choose a kids' meal with a toy, the caloric
      savings of a kids' meal that meets nutrition standards, and the degree to which
      these savings could result in weight gain averted per child per year. RESULTS:
      Using New York as a case study, the model estimates that, on a typical day, 5%
      (163,571) of children 0-12 years of age in New York could be affected by a toy
      ordinance. A child who typically consumes fast food two times per week could
      avoid gaining approximately 2 pounds per year with an ordinance requiring kids'
      meals to be <=550 calories. The amount of weight gain averted would vary
      according to the calorie limit set by the law and the frequency of consumption
      per week. CONCLUSIONS: Our model indicates that a reduction in calories in kids'
      meals with toy giveaways has the potential to positively affect weight gain in a
      considerable percentage of children. Limitations of the model are considered.

PMID- 24304431
TI  - My life with RE.

PMID- 24304432
TI  - Surgical versus medical treatment for refractory epilepsy: outcomes beyond
      seizure control.
AB  - Nearly one third of patients with epilepsy become medically intractable, and the
      likelihood of achieving seizure freedom decreases with each additional medication
      trial. For appropriately chosen patients, epilepsy surgery affords the
      opportunity to achieve seizure freedom and potentially wean off medications.
      Epilepsy surgery, as with medical management, is not without adverse effects; to
      counsel patients wisely, practitioners need to understand the advantages and
      disadvantages of both. Randomized controlled trials in temporal lobe epilepsy
      reveal that epilepsy surgery achieves superior outcome compared to continued
      medical management. Although seizure freedom is the ultimate goal of any therapy,
      it represents a single outcome measure among a variety of other domains that
      affect patient welfare. It is imperative that providers understand the patient
      variables that affect these outcome measures and how these measures impact each
      other. Because the data comparing surgical therapy versus medical management for
      refractory epilepsy are limited, we review the available evidence comparing
      outcomes beyond seizure freedom including quality of life, cognition,
      psychosocial function, mortality, and financial costs. 

PMID- 24304433
TI  - Prognostic factors for subsequent epilepsy in children with febrile seizures.
AB  - OBJECTIVE: Epilepsy following febrile seizures (FS) has been estimated between 2%
      and 7%. It concerns a prospective study in a large sample of children with a long
      term follow-up. The aim of this study is to identify the prognostic factors that
      can lead children with FS to epilepsy. METHODS: Children with a first episode of
      FS were included. We gathered information about prenatal and perinatal history,
      family history of FS and epilepsy in first- and second degree relatives, age at
      the time of the initial FS, dates of FS recurrences, focality, duration of the FS
      and recurrent episodes within the same febrile illness, height and duration of
      fever prior to the seizure, cause of the fever, and frequency of febrile
      illnesses. Patients were seen every 4-6 months and also at each recurrence. KEY
      FINDINGS: A group of 560 children with a first FS met all entry criteria.
      Epilepsy was recorded at 5.4%. Statistical analysis was performed between
      children with epilepsy and those with no afebrile seizure. We analyzed FS
      recurrences in accordance with the occurrence of epilepsy. From the third FS
      recurrence and beyond, only focality continued to have prognostic value.
      SIGNIFICANCE: Main prognostic factors for the development of epilepsy after FS
      are: (1) complex FS that increased the risk for epilepsy 3.6 times, (2) age at
      onset of FS beyond the third year of life that raised the risk 3.8 times, (3)
      positive family history of epilepsy 7.3 times, and (4) multiple episodes of FS
      about 10 times. Focality at the first and the second FS recurrence increased the
      risk of epilepsy about 9.7 and 11.7 times, respectively. Focality was the only
      factor that continued to be significant in further FS recurrences. A prognostic
      profile of each child with FS would be very useful for the follow-up of these
      children.

PMID- 24304434
TI  - Hippocampal volume loss following childhood convulsive status epilepticus is not
      limited to prolonged febrile seizures.
AB  - PURPOSE: Childhood convulsive status epilepticus (CSE), in particular prolonged
      febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS).
      Previous studies have shown that hippocampal injury occurs in the acute phase
      immediately following CSE, but little is known about the longer term evolution of
      such injury. This study aimed to investigate the longer term outcome of childhood
      CSE with sequential magnetic resonance imaging (MRI) looking for progressive
      hippocampal injury during the first year post-CSE. METHODS: Eighty children (0.18
      15.5 years) underwent brain MRI 1 month post-CSE, 50 with a repeat MRI at 6
      months and 46 with repeat MRI at 12 months post-CSE. Thirty-one control subjects
      without neurologic problems had a single brain MRI for comparison. Hippocampal
      volumes were measured from each MRI scan by two independent observers, and
      hippocampal growth rates were estimated in each patient with suitable imaging.
      KEY FINDINGS: Hippocampal volume loss was found in 20-30% of patients and was not
      associated with the etiology or clinical features of CSE, including seizure
      duration or focality. A borderline association was found between a history of
      previous seizures (p = 0.063) and the number of previous febrile seizures (p =
      0.051), suggesting that multiple insults may be important in the pathogenesis of
      progressive hippocampal injury. SIGNIFICANCE: It is apparent that progressive
      hippocampal damage can occur after CSE of any etiology and is not limited to PFS.
      Repeated seizures may play an important role, but further follow-up is needed to
      determine any other risk factors and proportion of children showing initial
      volume loss progress to clinical MTS and temporal lobe epilepsy.

PMID- 24304436
TI  - Epilepsy in TSC: certain etiology does not mean certain prognosis.
AB  - PURPOSE: Prevalence and long-term outcome of epilepsy in tuberous sclerosis
      complex (TSC) is reported to be variable, and the reasons for this variability
      are still controversial. METHODS: We reviewed the clinical characteristics of
      patients with TSC who were regularly followed since 2000 at the San Paolo
      Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts
      we collected data about age at epilepsy onset, seizure frequency and seizure
      type, history of infantile spasms (IS), epileptic syndrome, evolution to
      refractory epilepsy or to seizure freedom and/or medication freedom,
      electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings,
      cognitive outcome, and genetic background. KEY FINDINGS: Among the 160 subjects
      (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure
      free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had
      a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their
      lives. Epilepsy onset in the first year of life with IS and/or focal seizures was
      characteristic of the drug-resistant group of patients, as well as cognitive
      impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients,
      4.4%) experienced a seizure only once; all of them had normal cognition.
      SIGNIFICANCE: Although epilepsy management can be challenging in TSC, more than
      one third of patients had their seizures controlled: through monotherapy in 56%
      and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and
      were off medication. Identifying predictive features of epilepsy and cognitive
      outcome can ensure better management for patients with TSC and delineate genotype
      phenotype correlations.

PMID- 24304435
TI  - Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic
      structural abnormalities.
AB  - PURPOSE: Neurobehavioral comorbidities are common in pediatric epilepsy with
      enduring adverse effects on functioning, but their neuroanatomic underpinning is
      unclear. Striatal and thalamic abnormalities have been associated with childhood
      onset epilepsies, suggesting that epilepsy-related changes in the subcortical
      circuit might be associated with the comorbidities of children with epilepsy. We
      aimed to compare subcortical volumes and their relationship with age in children
      with complex partial seizures (CPS), childhood absence epilepsy (CAE), and
      healthy controls (HC). We examined the shared versus unique structural-functional
      relationships of these volumes with behavior problems, intelligence, language,
      peer interaction, and epilepsy variables in these two epilepsy syndromes.
      METHODS: We investigated volumetric differences of caudate, putamen, pallidum,
      and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study
      subjects underwent structural magnetic resonance imaging (MRI), intelligence, and
      language testing. Parent-completed Child Behavior Checklists provided behavior
      problem and peer interaction scores. We examined the association of age,
      intelligence quotient (IQ), language, behavioral problems, and epilepsy variables
      with subcortical volumes that were significantly different between the children
      with epilepsy and HC. KEY FINDINGS: Both children with CPS and CAE exhibited
      significantly smaller left thalamic volume compared to HC. In terms of
      developmental trajectory, greater thalamic volume was significantly correlated
      with increasing age in children with CPS and CAE but not in HC. With regard to
      the comorbidities, reduced left thalamic volumes were related to more social
      problems in children with CPS and CAE. Smaller left thalamic volumes in children
      with CPS were also associated with poor attention, lower IQ and language scores,
      and impaired peer interaction. SIGNIFICANCE: Our study is the first to directly
      compare and detect shared thalamic structural abnormalities in children with CPS
      and CAE. These findings highlight the vulnerability of the thalamus and provide
      important new insights on its possible role in the neurobehavioral comorbidities
      of childhood-onset epilepsy.

PMID- 24304437
TI  - Positron emission tomography with alpha-[11C]methyl-L-tryptophan in tuberous
      sclerosis complex-related epilepsy.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is often associated with cerebral
      tubers and medically intractable epilepsy. We reevaluated whether increased
      uptake of alpha-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is
      associated with tuber epileptogenicity. METHODS: We included 12 patients (six
      male, 4-53 years old) with TSC and refractory seizures who were evaluated for
      epilepsy surgery in our center, including video-electroencephalographic (EEG)
      monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR
      MRI), and positron emission tomography (PET) with alpha-[(11) C]methyl-l
      tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG
      recording. AMT uptake in each tuber was visually evaluated on PET coregistered
      with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also
      calculated. Sensitivity and specificity values of AMT-PET in the detection of
      epileptogenic lesions were obtained, using the available electroclinical and
      neuroimaging evidence as the gold standard for epileptogenicity. RESULTS: A total
      of 126 tubers were identified. Two of 12 patients demonstrated a tuber with
      clearly increased AMT uptake, one of whom also showed a subtle increased AMT
      uptake in another contralateral tuber. Four other patients showed only subtle
      increased AMT uptake. The only two tubers with clearly increased AMT uptake
      proved to be epileptogenic based on intracerebral EEG data, whereas none of the
      tubers associated with subtle increased AMT uptake were involved at ictal onset.
      In a per-patient approach, this yielded a sensitivity of clearly increased AMT
      uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the
      per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3
      34%) and 100% (95% CI: 97-100%), respectively. SIGNIFICANCE: AMT-PET is a
      specific neuroimaging technique in the identification of epileptogenic tubers in
      TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still
      deserves to be considered according to the challenging complexity of epilepsy
      surgery in tuberous sclerosis.

PMID- 24304438
TI  - Electroencephalography/functional magnetic resonance imaging responses help
      predict surgical outcome in focal epilepsy.
AB  - PURPOSE: Simultaneous electroencephalography/functional magnetic resonance
      imaging (EEG/fMRI) recording can noninvasively map in the whole brain the
      hemodynamic response following an interictal epileptic discharge. EEG/fMRI is
      gaining interest as a presurgical evaluation tool. This study aims to determine
      how hemodynamic responses related to epileptic activity can help predict surgical
      outcome in patients considered for epilepsy surgery. METHODS: Thirty-five
      consecutive patients with focal epilepsy who had significant hemodynamic
      responses and eventually surgical resection, were studied. The statistical map of
      hemodynamic responses were generated and co-registered to postoperative anatomic
      imaging. Patients were classified into four groups defined by the relative
      relationship between the location of the maximum hemodynamic response and the
      resection: group 1, fully concordant; group 2, partially concordant; group 3,
      partially discordant; and group 4, fully discordant. These findings were
      correlated with surgical outcome with at least 12-month follow-up. KEY FINDINGS:
      Ten patients in group 1 had the maximum t value (t-max) inside the resection;
      nine in group 2 had the t-max outside but close to the resection and the cluster
      with t-max overlapped the resection; five in group 3 had the t-max remote from
      resection, but with another less significant cluster in the resection; and 11 in
      group 4 had no response in the resection. The degree of concordance correlated
      largely with surgical outcome: a good surgical outcome (Engel's class I) was
      found in 7 of 10 patients of group 1, 4 of 9 of group 2, 3 of 5 of group 3, and
      only 1 of 11 of group 4. These results indicate that the partially concordant and
      partially discordant groups are best considered as inconclusive. In contrast, in
      the fully concordant and fully discordant groups, the sensitivity, specificity,
      positive predictive value, and negative predictive value were high, 87.5%, 76.9%,
      70%, and 90.9%, respectively. SIGNIFICANCE: This study demonstrates that
      hemodynamic responses related to epileptic activity can help delineate the
      epileptogenic region. Full concordance between maximum response and surgical
      resection is indicative of seizure freedom, whereas a resection leaving the
      maximum response intact is likely to lead to a poor outcome. EEG/fMRI is
      noninvasive but is limited to patients in whom interictal epileptic discharges
      can be recorded during the 60-90 min scan.

PMID- 24304439
TI  - Dysembryoplastic neuroepithelial tumors: a model for examining the effects of
      pathology versus seizures on cognitive dysfunction in epilepsy.
AB  - PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) provide a unique model
      for studying the effects of seizures on cognitive development. Epilepsy and
      antiepileptic medications are prominent features in the lives and schooling of
      people who develop seizures in childhood. People with an adult onset share the
      same underlying brain pathology, but their childhood development is unaffected by
      seizures. Therefore, DNTs provide a model to examine the specific influence of
      seizures and their treatment on cognitive development, over and above the effects
      of the underlying pathology in epilepsy. METHODS: We examined the
      neuropsychological characteristics of 56 adults with DNT and medically
      intractable epilepsy (mean age 32.7 years). Twenty-two adults (39%) had an age of
      onset of epilepsy before the age of 12 years (childhood-onset group). Scores on
      tests of intelligence (Verbal IQ and Performance IQ), reading, working memory,
      verbal learning, verbal recall, visual learning, and expressive and receptive
      language ability were analyzed. KEY FINDINGS: There were no significant
      localization effects (right vs. left vs. extratemporal) on any of the
      neuropsychological test scores. In the group as a whole, the neuropsychological
      test scores were significantly lower than healthy, age-matched controls on
      measures of Verbal IQ (p < 0.01), naming p < 0.01, verbal learning (p < 0.01),
      and working memory (p < 0.05). The childhood-onset group had significantly lower
      scores on the measures of Verbal IQ (p < 0.01), Performance IQ (p < 0.05),
      reading (p < 0.05), naming (p = 0.05), and verbal retention (p < 0.05) than those
      with an onset of seizures at the age of 12 or older. SIGNIFICANCE: The
      traditional pattern of lateralized memory deficits seen in people with
      hippocampal sclerosis may not be present in people with temporal lobe epilepsy
      associated with a DNT. The presence of seizures and their treatment in early
      childhood may adversely influence the development of these core cognitive
      abilities, resulting in patterns of cognitive deficits that remain apparent in
      adulthood.

PMID- 24304440
TI  - Authors' response to letter by A. Mazarati.

PMID- 24304441
TI  - Behavioral and neuroendocrine assays for studying epilepsy-associated depression.

PMID- 24304442
TI  - T lymphocytes export proteasomes by way of microparticles: a possible mechanism
      for generation of extracellular proteasomes.
AB  - The 20S proteasome is almost exclusively localized within cells. High levels of
      extracellular proteasomes are also found circulating in the blood plasma of
      patients suffering from a variety of inflammatory, autoimmune and neoplastic
      diseases. However, the origin of these proteasomes remained enigmatic. Since the
      proteome of microparticles, small membrane enclosed vesicles released from cells,
      was shown to contain proteasomal subunits, we studied whether intact proteasomes
      are actively released into the extracellular space. Using human primary T
      lymphocytes stimulated with CaCl2 and the calcium ionophore A23187 to induce
      membrane blebbing we demonstrate that microparticles contain proteolytically
      active 20S proteasomes as well as the proteasome activator PA28 and subunits of
      the 19S proteasome regulator. Furthermore, our experiments reveal that incubation
      of in vitro generated T lymphocyte-microparticles with sphingomyelinase results
      in the hydrolysis of the microparticle membranes and subsequent release of
      proteasomes from the vesicles. Thus, we here show for the first time that
      functional proteasomes can be exported from activated immune cells by way of
      microparticles, the dissolution of which may finally lead to the generation of
      extracellular proteasomes.

PMID- 24304443
TI  - Herniation of the gravid uterus through a mesoduodenal defect and concurrent
      omental hernia in a cow.
AB  - OBJECTIVES: To describe surgical treatment of herniation of the gravid uterus
      through the mesoduodenum, displacement of the descending duodenum around the
      gravid uterus, and concurrent herniation of the small and large intestines into
      the omental bursa in a cow. STUDY DESIGN: Clinical report. ANIMAL: Three-year
      old, five-month-pregnant Swiss Braunvieh cow. METHODS: Repositioning of the
      displaced uterus and descending duodenum without transection and anastomosis of
      the duodenum was performed through a right flank laparotomy. Concurrent
      displacement of a large portion of the small and large intestines into the
      omental bursa was not associated with intestinal strangulation and was corrected
      manually. The defects in the omentum and mesoduodenum were sutured. RESULTS:
      There were no postoperative complications, and the cow was healthy at discharge
      from the clinic 1 week after surgery. Telephone follow-up revealed that the cow
      had delivered a live calf and was producing a normal amount of milk. The cow was
      slaughtered 14 months after the surgery because of an udder problem. CONCLUSIONS:
      Herniation of the gravid uterus through a tear in the mesoduodenum with
      subsequent displacement of the descending duodenum around the uterus combined
      with internal omental herniation caused nonspecific clinical signs and no ileus.
      Exploratory laparotomy in an early stage of pregnancy facilitated reduction of
      the displaced uterus without transection of the descending duodenum.

PMID- 24304445
TI  - The career success scale in nursing: psychometric evidence to support the Chinese
      version.
AB  - AIM: The purpose of this study was to examine the psychometric properties of the
      11-item Chinese version of the Career Success Scale. BACKGROUND: Nurses play an
      important role in the healthcare system. Opportunities to achieve success and
      satisfaction from one's career affect the retention and stability of the nursing
      workforce. The Career Success Scale was originally developed in English and has
      been translated into Chinese. Psychometric testing of the Chinese Career Success
      Scale for measuring career success in nurses has not been performed. DESIGN: A
      cross-sectional survey was conducted. METHOD: A convenience sample of 1148
      clinical nurses were recruited from 10 level-3 hospitals in Guangdong Province,
      mainland China, from December 2010-December 2011. RESULTS: Results indicated that
      the Chinese Career Success Scale demonstrated good internal consistency and test
      retest reliability. Principal component analysis supported the three-factor
      structure of the original instrument: Career Satisfaction, Perceived within
      Organization Competitiveness and Perceived External Organization Competitiveness.
      There were significant correlations among the three factors, which demonstrated
      the good construct validity of the Chinese version of this scale. CONCLUSION: The
      Chinese Career Success Scale appears to be a reliable and valid instrument. It
      has the potential to be used to measure nurses' career success in mainland China.
      The findings will be useful for nurse leaders and policymakers in the evaluation
      of nurses' self-perceived career success and to develop strategies to promote
      nurse retention and career development.

PMID- 24304444
TI  - Combined treatment of rapamycin and dietary restriction has a larger effect on
      the transcriptome and metabolome of liver.
AB  - Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to
      increase lifespan. To investigate whether Rapa and DR affect similar pathways in
      mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a
      combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the
      liver. The principal component analysis shows that Rapa and DR are distinct
      groups. Over 2500 genes are significantly changed with either Rapa or DR when
      compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar
      observation was made when genes were grouped into pathways; two-thirds of the
      pathways were uniquely changed by DR or Rapa. The metabolome shows an even
      greater difference between Rapa and DR; no metabolites in Rapa-treated mice were
      changed significantly from AL mice, whereas 173 metabolites were changed in the
      DR mice. Interestingly, the number of genes significantly changed by Rapa + DR
      when compared with AL is twice as large as the number of genes significantly
      altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa
      on the liver are quite different and a combination of Rapa and DR results in
      alterations in a large number of genes and metabolites that are not significantly
      changed by either manipulation alone, suggesting that a combination of DR and
      Rapa would be more effective in extending longevity than either treatment alone. 

PMID- 24304446
TI  - Cardiovascular morbidity and mortality in surgically treated hyperthyroidism - a
      nation-wide cohort study with a long-term follow-up.
AB  - OBJECTIVE: Previous studies suggest that patients with hyperthyroidism remain at
      an increased risk of cardiovascular morbidity even after restoring euthyroidism.
      The mechanisms of the increased risk and its dependency on the different
      treatment modalities of hyperthyroidism remain unclear. The aim of this long-term
      follow-up study was to compare the rate of hospitalizations for cardiovascular
      causes and the mortality in hyperthyroid patients treated surgically with an age-
      and gender-matched reference population. PATIENTS AND MEASUREMENTS: A population
      based cohort study was conducted among 4334 hyperthyroid patients (median age 46
      years) treated with thyroidectomy in 1986-2007 in Finland and among 12,991
      reference subjects. Firstly, the hospitalizations due to cardiovascular diseases
      (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new
      hospitalization due to CVDs after the thyroidectomy were calculated in Cox
      regression analysis adjusted with the prevalent CVDs at the time of
      thyroidectomy. RESULTS: The risk of hospitalization due to all CVDs started to
      increase already 5 years before the thyroidectomy, and by the time of the
      operation, it was 50% higher in the hyperthyroid patients compared to the
      controls (P < 0.001). After the thyroidectomy, the hospitalizations due to all
      CVDs (HR 1.15), hypertension (HR 1.23), heart failure (HR 1.17) and valvular
      diseases or cardiomyopathies (HR 1.55) remained more frequent among the patients
      than among the controls for 20 years after thyroidectomy. The increased morbidity
      was not clearly related to the aetiology of hyperthyroidism. Despite the
      increased CVD morbidity among the patients, there was no difference in
      cardiovascular mortality. CONCLUSIONS: The present study shows that
      hyperthyroidism increases the risk of hospitalization due to CVDs and the risk is
      sustained up to two decades after effective surgical treatment. However, there
      was no excess CVD mortality in the middle-aged patient cohort studied.

PMID- 24304447
TI  - The mechanism of enhanced defecation caused by the ghrelin receptor agonist,
      ulimorelin.
AB  - BACKGROUND: Discovery of adequate pharmacological treatments for constipation has
      proven elusive. Increased numbers of bowel movements were reported as a side
      effect of ulimorelin treatment of gastroparesis, but there has been no
      investigation of the site of action. METHODS: Anesthetized rats were used to
      investigate sites and mechanisms of action of ulimorelin. KEY RESULTS:
      Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h)
      increase in colorectal propulsive activity and expulsion of colonic contents.
      This was prevented by cutting the nerves emerging from the lumbosacral cord, by
      the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin
      receptor. The effect of intravenous ulimorelin was mimicked by direct application
      of ulimorelin (5 MUg) to the lumbosacral spinal cord. CONCLUSIONS & INFERENCES:
      Ulimorelin is a potent prokinetic that causes propulsive contractions of the
      colorectum by activating ghrelin receptors of the lumbosacral defecation centers.
      Its effects are long-lasting, in contrast with other colokinetics that target
      ghrelin receptors.

PMID- 24304448
TI  - Brewer's yeast and sugarcane yeast as protein sources for dogs.
AB  - Brewer's yeast (BY), autolysed sugarcane yeast (ASCY) and integral sugar cane
      yeast (ISCY) were studied in two experiments as ingredients for dog diets. In the
      first experiment, 28 dogs were randomly assigned to four diets; one reference
      diet and three test diets containing 15% of BY, ASCY or ISCY and 85% of the
      reference diet (as-fed basis). The digestibilities of the yeasts were calculated
      by the substitution method. In the second experiment, 35 dogs were randomized to
      five diets with similar chemical composition but different levels of sugarcane
      yeast inclusion (0%, 7.5% ASCY, 15% ASCY, 7.5% ISCY and 15% ISCY). In both
      experiments, the coefficient of total tract apparent digestibility (CTTAD) of
      nutrients was determined through total collection of faeces. During experiment,
      two additional analyses of food palatability, nitrogen balance and urea
      postprandial responses were performed. The data were submitted to analysis of
      variance, and the means were compared by orthogonal or polynomial contrasts or
      Tukey's test (p < 0.05). In experiment 1, CTTAD of protein was lower for both
      sugarcane yeasts than for BY (p = 0.012), as was metabolizable energy content (p
      = 0.025). In experiment 2, a linear reduction in energy digestibility with ASCY
      inclusion (p = 0.05) was verified. Furthermore, faecal score and DM content were
      reduced with ISCY inclusion (p < 0.003). No effect of yeast inclusion on nitrogen
      balance or postprandial urea response was found. Also, the inclusion of 7.5% of
      ASCY or ISCY increased diet palatability (p < 0.01). Yeasts present adequate
      digestibility by dogs, but its effect on faecal formation needs to be considered.
      No clear advantage for the use of ASCY over ISCY was found. In conclusion, we
      find that sugarcane yeast is suitable for inclusion in dog food and can enhance
      the overall palatability of the diet. 

PMID- 24304449
TI  - Examining the positive effects of rapport building: when and why does rapport
      building benefit adult eyewitness memory?
AB  - Most investigative interviewing protocols recommend building rapport with
      cooperative adult witnesses to increase the accuracy of their reports. Although a
      few recent studies support the benefits of rapport building on adult witness
      recall, no study has examined whether the timing of rapport in relation to post
      event misinformation affects recall accuracy, and whether these effects are
      related to witness anxiety levels throughout the interview. The present study
      provided two hundred and thirty-three undergraduates with a videotaped mock crime
      followed by building high or low rapport either before or after they received
      post-event misinformation. All witnesses were then interviewed about the mock
      crime. Results indicated that high rapport before misinformation increased the
      amount of accurate information reported in a subsequent witness interview
      compared to low rapport. However, these recall benefits were not due to a
      reduction in anxiety. Theoretical implications and practical recommendations for
      police interviewing practices are discussed.

PMID- 24304450
TI  - Synthesis, properties, and redox behavior of tetracyanobutadiene and
      dicyanoquinodimethane chromophores bearing two azulenyl substituents.
AB  - Acetylene derivatives with an azulenyl group at both terminals have been prepared
      by palladium-catalyzed alkynylation under Sonogashira-Hagihara conditions. These
      alkynes reacted with tetracyanoethylene and 7,7,8,8-tetracyanoquinodimethane in a
      formal [2 + 2] cycloaddition-retroelectrocyclization reaction to afford the
      corresponding new tetracyanobutadienes (TCBDs) and dicyanoquinodimethanes
      (DCNQs), respectively, in excellent yields. Intramolecular CT absorption bands
      were found in the UV-vis spectra of the novel chromophores, and CV and DPV showed
      that they exhibited a reversible two-stage reduction wave, due to the
      electrochemical reduction of TCBD and DCNQ moieties. Color changes were also
      observed during the electrochemical reduction. 

PMID- 24304451
TI  - The inhibition of hepatitis B virus by APOBEC cytidine deaminases.
AB  - APOBEC3 (A3) cytidine deaminases are a family of enzymes that have been shown to
      inhibit the replication of HIV-1 and other retroviruses as part of the innate
      immune responses to virus infection. They can also hyperedit HBV DNA and inhibit
      HBV replication. Although A3 proteins are present at low levels in normal liver,
      A3 gene expression is highly stimulated by both interferon-alpha and interferon
      gamma. A3 deaminases are incorporated into nascent HBV capsids where they cleave
      amino groups from cytidine bases converting them to uracil in newly synthesized
      DNA following reverse transcription of pregenomic RNA. This modified HBV DNA is
      susceptible to degradation, or alternatively, numerous G-to-A nucleotide
      mutations are incorporated into positive-strand viral DNA disrupting coding
      sequences. A3 proteins in which the cytidine deaminase activity has been lost can
      also inhibit HBV replication, suggesting that there may be more than one way in
      which inhibition can occur. There is also evidence that A3 proteins might play a
      role in the development of hepatocellular carcinoma during chronic HBV infection.

PMID- 24304452
TI  - Regression of liver fibrosis is progressive after sustained virological response
      to HCV therapy in patients with hepatitis C and HIV coinfection.
AB  - There are few data about the long-term histological outcome of HIV-/HCV
      coinfected patients after therapy with interferon and ribavirin. We performed an
      observational study of 216 patients who received therapy against HCV and who had
      at least three successive transient elastographies (TE) during the follow-up. The
      primary endpoint was confirmed fibrosis regression, defined as a reduction of at
      least 1 point in Metavir fibrosis score, confirmed and without worsening in
      successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82
      (38%) achieved sustained virological response (SVR), without differences in
      baseline fibrosis or time of follow-up. Confirmed fibrosis regression was
      observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the
      likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51
      and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41
      for no SVR patients (P < 0.01, log-rank test at any time point). Progressive
      regression, defined as continuous improvement in successive TE, was observed in
      62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a
      Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33-7.57; P < 0.01) and a
      younger age (HR, 1.14; 95% CI, 1.05-1.25; P < 0.01; per year) were associated
      with fibrosis regression. This study confirms that the rate of liver fibrosis
      regression increases during the follow-up after SVR to interferon therapy in HIV
      /HCV-coinfected patients.

PMID- 24304453
TI  - Valuable antiviral therapeutic options for the treatment of chronic hepatitis C
      patients with thrombocytopenia.
AB  - Thrombocytopenia in patients with chronic hepatitis C may represent an obstacle
      for the initiation of antiviral treatment. The aim of this study was to evaluate
      factors predictive of successful pegylated interferon (PEG-IFN) alpha2b and
      ribavirin (RBV) treatment for patients with thrombocytopenia with no history of
      splenectomy or partial splenic embolization. One hundred and fifty-one chronic
      hepatitis C patients (genotype 1: n = 110, genotype 2: n = 41) with TCP (<100 *
      10(9) /L) at baseline were enrolled. Pretreatment variables included interleukin
      28B (IL28B) genotype (rs8099917) and homoeostasis model assessment of insulin
      resistance score (HOMA-IR). The kinetics of haemoglobin and platelets according
      to the inosine triphosphatase (ITPA) genotype (rs1127354) were investigated.
      Sustained virological response (SVR) was significantly more frequent in hepatitis
      C virus (HCV) genotype 2 (65.9%) than in genotype 1 (34.5%) patients (P <
      0.0001). Multiple logistic regression analysis of HCV genotype 1 extracted IL28B
      TT genotype [odds ratio (OR) 5.97, P = 0.006] and HOMA-IR <2.5 (OR 7.14, P =
      0.0016) as significant independent pretreatment predictors of SVR. The analyses
      of HCV genotype 2 showed that HOMA-IR was significantly related to SVR, but IL28B
      genotype was not. Patients with ITPA CC genotype showed a significant haemoglobin
      reduction and lower degree of platelets decrease than those with ITPA CA/AA
      genotypes. The most common reason for premature discontinuation of treatment was
      the development of hepatocellular carcinoma (n = 8, 5.3%). In conclusion, HOMA-IR
      is a useful predictor of SVR for patients with thrombocytopenia infected with HCV
      genotype 1 or 2 treated with PEG-IFNalpha2b and RBV. The inclusion of IL28B, ITPA
      genotypes and HOMA-IR adds valuable therapeutic information.

PMID- 24304454
TI  - All-oral, interferon-free treatment for chronic hepatitis C: cost-effectiveness
      analyses.
AB  - Interferon-based standard of care treatments (SOC) for chronic hepatitis C are
      unable to provide high cure rates in certain subgroups of the infected population
      and can cause debilitating side effects. Clinical trials evaluating all-oral,
      interferon-free treatments have demonstrated high rates of sustained virologic
      response with no resistance or major adverse events in most populations. As these
      drug regimens move towards FDA approval, it will be important to assess their
      cost-effectiveness in addition to their clinical efficacy. A decision-analytic
      Markov model with a lifetime, societal perspective was used to evaluate the cost
      effectiveness of a generalized all-oral drug regimen compared to SOC by modelling
      the progression of a 50-year-old, HCV-positive cohort through disease natural
      history and treatment. In base case analysis, all-oral treatment dominated SOC
      across a range of willingness-to-pay (WTP) thresholds with an incremental cost
      effectiveness ratio (ICER) of US$44,514/quality-adjusted life year (QALY). In
      sensitivity analyses, the model was sensitive to all-oral drug costs as well as
      rates of SVR and treatment uptake among noncirrhotic subjects, but robust to
      variations in all other parameters. All-oral treatment was most cost-effective
      among genotype 1 subjects but remained cost-effective for genotypes 2 and 3 at
      WTP thresholds >=$80,000/QALY. Quality-adjusted life years gained per dollar
      spent were maximized in younger treatment cohorts. Using this model, the degree
      of cost-effectiveness depended on the WTP threshold and the final cost set for
      approved drug combinations.

PMID- 24304455
TI  - Inosine triphosphatase deficiency helps predict anaemia, anaemia management and
      response in chronic hepatitis C therapy.
AB  - Anaemia frequently complicates peginterferon/ribavirin therapy for chronic
      hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or
      erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase
      (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose
      reduction; however, their impact in real-life clinic patient cohorts remains to
      be defined. We studied 193 clinic patients with chronic hepatitis C infection of
      mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with
      peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354
      and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present.
      Estimated ITPA deficiency was graded on severity (0-3, no
      deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable
      models tested the association with anaemia at 4 weeks of treatment [including
      decline in haemoglobin (g/dL); haemoglobin <10 g/dL and haemoglobin decline >3
      g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response
      (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with
      less reduction in haemoglobin level (P <0.001; R(2) = 0.34), less ribavirin dose
      reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53;
      (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02
      2.83); P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In
      this clinical cohort, ITPA deficiency helped predict the risk of on-treatment
      anaemia, ribavirin dose reduction, need for EPO support and was associated with
      SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for
      ITPA deficiency may have clinical utility.

PMID- 24304456
TI  - Modified spleen stiffness measurement by transient elastography is associated
      with presence of large oesophageal varices in patients with compensated hepatitis
      C virus cirrhosis.
AB  - To evaluate the accuracy of liver transient elastography (TE), spleen TE and
      other noninvasive tests (AAR, APRI score, platelet count, platelet/spleen ratio)
      in predicting the presence and the size of oesophageal varices in compensated
      hepatitis C virus (HCV) cirrhosis, we studied 112 consecutive patients with
      compensated HCV cirrhosis who underwent biochemical tests, gastrointestinal
      endoscopy, liver TE and spleen TE by Fibroscan((r)) (Echosens, Paris, France)
      using a modified software version with a range between 1.5 and 150 kPa. Spleen TE
      was not reliable in 16 patients (14.3%). Among the 96 patients with a valid
      measurement (69.8% men, mean age: 63.2 +/- 9.5 years), 43.7% had no oesophageal
      varices, 29.2% had grade 1% and 27.1% had grade 2 or grade 3 oesophageal varices.
      Patients with values of 75 kPa by standard spleen TE had mean values of modified
      spleen TE of 117 kPa (range: 81.7-149.5). Linear regression revealed a
      significant correlation between modified spleen TE and oesophageal varix size (r
      = 0.501; beta: 0.763, SE: 0.144; P < 0.001). On univariate analysis, the
      variables associated with grade 2/grade 3 oesophageal varices were AAR score,
      APRI score, platelet/spleen ratio, liver TE and modified spleen TE. On
      multivariate analysis, only modified spleen TE (OR: 1.026; 95% CI: 1.007-1.046; P
      = 0.006) and AAR (OR: 14.725; 95% CI: 1.928-112.459; P = 0.010) remained
      independently associated with grade 2/grade 3 oesophageal varices.
      Platelet/spleen ratio was the best predictor of oesophageal varices area under
      the ROC curve (AUROC: 0.763, cut-off: 800, sensitivity: 74%, specificity: 70%),
      while modified spleen TE was more accurate in predicting grade 2/grade 3
      oesophageal varices (AUROC: 0.82, cut-off: 54.0 kPa, sensitivity: 80%,
      specificity: 70%). Portal hypertension increases spleen stiffness, and the
      measurement of modified spleen TE is an accurate, noninvasive tool for predicting
      the presence of large oesophageal varices in patients with compensated HCV
      cirrhosis.

PMID- 24304457
TI  - Maternal immunization promotes the immune response of neonates towards hepatitis
      B vaccine.
AB  - Infants infected with hepatitis B virus (HBV) face the risk of developing severe
      complications. Unfortunately, in spite of universal vaccination programmes, 5% or
      more of vaccinated newborns still do not achieve protective levels of anti
      hepatitis B virus surface antigen titres (anti-HBs). The aim of this study was to
      use animal experiments and population-based research to determine whether
      maternal vaccination against HBV affects the outcome of neonatal vaccination. Six
      sows and 53 newborn piglets were used for this study and randomly assigned to the
      vaccination group (three 20 MUg doses of recombinant HBV vaccine). All the
      piglets were followed up to 10 weeks of age, and peripheral blood was withdrawn
      for measurement of anti-HBs. A cross-sectional study was also conducted on 449
      mothers with infants. A structured questionnaire was used to collect demographic,
      medical and maternal data, and their peripheral blood was collected for
      measurement of anti-HBs. The results of animal experiments demonstrated that
      nonvaccinated piglets born to vaccinated sows and nonvaccinated piglets born to
      nonvaccinated sows were negative for anti-HBs. Repeated measures analysis of
      variance showed that the titres of anti-HBs in vaccinated piglets born to
      vaccinated sows were significantly higher than in vaccinated piglets born to
      nonvaccinated sows (P < 0.05). In a population-based study, a cumulative logistic
      regression analysis showed that the strongest influences on neonatal anti-HBs
      titres were delay of the first vaccination dose [OR = 3.02(95% CI: 1.72-5.30)]
      and maternal anti-HBs titres [OR = 2.48(95% CI: 2.03-3.04)]. In conclusion, high
      maternal anti-HBs titres can enhance the response to HBV vaccination in infants.

PMID- 24304458
TI  - Full genome ultra-deep pyrosequencing associates G-to-A hypermutation of the
      hepatitis B virus genome with the natural progression of hepatitis B.
AB  - Human APOBEC3 (A3) cytosine deaminases are antiviral restriction factors capable
      of editing the genome the hepatitis B virus (HBV). Despite the importance of the
      human A3 protein family for the innate immune response little is known about the
      clinical relevance for hepatitis B. The aim of this study was to utilize ultra
      deep pyrosequencing (UDPS) data to analyse the phenomenon of G-to-A hypermutation
      of the complete HBV genome and to relate it to fundamental characteristics of
      patients with chronic hepatitis B. By analysing the viral population of 80
      treatment naive patients (47 HBeAg-positive and 33 HBeAg-negative), we identified
      an unequal distribution of G-to-A hypermutations across the genome. Our data
      indicate that G-to-A hypermutation occurs predominantly in a region between
      nucleotide positions 600 and 1800 a region which is usually single stranded in
      matured HBV particles. This implies that A3 likely edits HBV in the virion.
      Hypermutation rates for HBeAg-negative patients were more than 10-fold higher
      than those of HBeAg-positive patients. For HBeAg-negative patients higher
      hypermutation rates were significantly associated with the degree of fibrosis.
      Additionally, we found that for HBeAg-positive chronic hepatitis G-to-A
      hypermutation rates were significantly associated with the relative prevalence of
      the G1764A mutation, which is related to HBeAg seroconversion. In total, our data
      imply an important association of hypermutation mediated by A3 deaminases with
      the natural progression of chronic hepatitis B infections both in terms of HBeAg
      seroconversion and disease progression towards cirrhosis. 

PMID- 24304459
TI  - A paucity of liver disease in Canadian Inuit with chronic hepatitis B virus,
      subgenotype B6 infection.
AB  - Clinical observations suggest that chronic hepatitis B virus (HBV) infections in
      the Canadian Inuit are less often associated with serious adverse outcomes than
      has been described in other HBV-infected patient populations. The aim of this
      study was to document the clinical and biochemical features, liver-related
      morbidity and all-cause mortality in Canadian Inuit with chronic HBV infections.
      Administrative databases were reviewed for individuals identified as hepatitis B
      surface antigen (HBsAg) positive during a 1983-85 seroepidemiological survey of
      viral hepatitis in Baffin Island, Canada. An equal number of age- and gender
      matched HBsAg-negative individuals from the same communities served as controls.
      Baseline HBV viral loads, genotypes and specific mutations were compared in HBsAg
      positive survivors and nonsurvivors. A subset of surviving HBsAg-positive
      carriers were reassessed 25-30 years following their initial diagnosis for
      evidence of advanced liver disease and changes to their serological/virological
      findings. One hundred and forty four HBsAg-positive individuals were identified.
      All were Canadian Inuit. The mean age at diagnosis was 38 +/- 17 years and 69
      (61%) were male. Median follow-up was 23 years (range: 2-28 years). Viral
      quantitation from stored sera could be performed in 70 infected individuals. The
      median viral load was 4.3 log 10 IU/ml (range: 2.3-8.8 log 10 IU/ml), and all
      were genotype B, subgenotype B6. Liver biochemistry, morbidity and all-cause
      mortality rates were similar in HBsAg-positive carriers and controls. Following
      multivariate analyses, only age at diagnosis predicted mortality in HBsAg
      carriers. In a subset of 30 HBsAg-positive survivors who underwent follow-up
      assessments, clinical, biochemical and radiological examinations of the liver
      were essentially normal. 23/30 (77%) remained HBsAg positive and 17/19 (90%) HBV
      DNA positive. The genotype and prevalence of genomic mutations in this cohort
      remained largely unchanged, but quantifiable viral loads were significantly lower
      (P < 0.003). The results of this study suggest that chronic HBV infections in the
      Canadian Inuit are infrequently associated with serious adverse outcomes. Whether
      this finding reflects unique features of the host, presence or absence of
      external factors that influence the course of HBV and/or intrinsic properties of
      the HBV B6 subgenotype remains to be determined.

PMID- 24304460
TI  - Antiviral therapy in patients with hepatitis B virus-related hepatocellular
      carcinoma: is it ready for universal application?

PMID- 24304461
TI  - Early effect of essential hypertension on the left ventricular twist-displacement
      loop by two-dimensional ultrasound speckle tracking imaging.
AB  - OBJECTIVE: To investigate two-dimensional (2D) ultrasound speckle tracking
      imaging (STI) in the evaluation of the early changes in the left ventricular (LV)
      twist-displacement loop in patients with hypertension (EH). METHODS: Sixty-five
      EH patients with left ventricular normal geometry (LVN) - including 33 cases with
      non-left atrial enlargement (NLAE) and 32 cases with left atrial enlargement
      (LAE) - along with 45 healthy individuals were enrolled in this study. Basal and
      apical 2D LV short-axis images were acquired and analyzed to obtain the LV
      rotation (LVrot) and LV radial displacement. Once the LV twist and LV radial
      displacement were calculated, an LV twist-displacement loop was constructed.
      Group comparisons between peak twist (Ptw), twist at mitral valve opening
      (MVOtw), untwisting rate (Utw R), systolic radial displacement (SD), systolic
      slope (SS), isovolumic relaxation radial displacement (IVRD) and isovolumic
      relaxation slope (IVRS) were performed. RESULTS: (1) The Ptw and MVOTw were
      greater in the NLAE and LAE groups when compared to the normal group while the
      UTw R was lower in likewise comparison. (2) The LV twist was correlated to the
      radial displacement in systole and in the isovolumic relaxation period. The SS
      and IVRS were greater in the NLAE and LAE groups when compared to the normal
      group. CONCLUSIONS: The LV twist-displacement loop can be reconstructed
      noninvasively by 2D ultrasound STI. EH affects the systolic and early diastolic
      component of the twist-displacement loop by increasing the LV twist and
      decreasing the LV untwisting respectively impairing LV relaxation. The assessment
      of the LV twist-displacement loop may be useful in the evaluation of early
      features of LV dysfunction in EH patients.

PMID- 24304462
TI  - A retrospective analysis of the factors associated with hypercalcaemia in
      patients with advanced cancer.
AB  - Hypercalcaemia, a common complication of advanced cancer, causes multiple
      clinical symptoms, deteriorates patients' quality of life, and is associated with
      poor prognoses. This study aimed to identify the factors that may be associated
      with hypercalcaemia in advanced cancer by retrospectively reviewing the medical
      records of patients (n = 404) admitted to the palliative ward of the Kaohsiung
      Medical University Hospital, Taiwan, from 2006 to 2008. Patients' demographics,
      clinical data and symptoms were recorded. Seventy-nine of 404 patients had
      hypercalcaemia (19.6%), predominant in cases of head-and-neck cancer and
      haematological malignancies (P < 0.05), but not in those of bone metastases.
      Hypercalcaemia was associated with consciousness disturbances and leucocytosis (P
      < 0.05). We recommend that ionised (corrected) calcium levels be monitored
      clinically in patients with advanced cancer especially when consciousness
      disturbances are noted, or when head-and-neck or haematological malignancies are
      present. Testing of free calcium levels is also recommended in patients with
      leucocytosis. 

PMID- 24304463
TI  - Treatment of comorbid alcohol use disorders and depression with cognitive
      behavioural therapy and motivational interviewing: a meta-analysis.
AB  - BACKGROUND AND AIMS: To review published studies on the effectiveness of
      combining cognitive-behavioural therapy (CBT) and motivational interviewing (MI)
      to treat comorbid clinical and subclinical alcohol use disorder (AUD) and major
      depression (MDD) and estimate the effect of this compared with usual care.
      METHODS: We conducted systematic literature searches in PubMed, PsycINFO and
      Embase up to June 2013 and identified additional studies through cross-references
      in included studies and systematic reviews. Twelve studies comprising 1721
      patients met our inclusion criteria. The studies had sufficient statistical power
      to detect small effect sizes. RESULTS: CBT/MI proved effective for treating
      subclinical and clinical AUD and MDD compared with controls, with small overall
      effect sizes at post-treatment [g=0.17, confidence interval (CI)=0.07-0.28,
      P<0.001 for decrease of alcohol consumption and g=0.27, CI: 0.13-0.41, P<0.001
      for decrease of symptoms of depression, respectively]. Subgroup analyses revealed
      no significant differences for both AUD and MDD. However, digital interventions
      showed a higher effect size for depression than face-to-face interventions (g=
      0.73 and g=0.23, respectively, P=0.030). CONCLUSIONS: Combined cognitive
      behavioural therapy and motivational interviewing for clinical or subclinical
      depressive and alcohol use disorders has a small but clinically significant
      effect in treatment outcomes compared with treatment as usual.

PMID- 24304464
TI  - The use of absolute values improves performance of estimation formulae: a
      retrospective cross sectional study.
AB  - BACKGROUND: Estimation of Glomerular Filtration Rate (GFR) by equations such as
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Modification of
      Diet in Renal Disease (MDRD) is usually expressed as a Body Surface Area (BSA)
      indexed value (ml/min per 1.73 m2). This can have severe clinical consequences in
      patients with extreme body sizes, resulting in an underestimation in the case of
      obesity or an overestimation of GFR in the case of underweight patients. The aim
      of this study was to compare the performance of both estimation formula expressed
      in ml/min, instead of ml/min per 1.73 m2, with a reference method. METHODS:
      Retrospective single centre cross sectional study of 185 patients. GFR was
      measured with 51Cr-EDTA and estimated with CKD-EPI and MDRD. Bias, precision and
      accuracy of absolute estimated GFR was calculated. RESULTS: Bias of CKD-EPI and
      MDRD formulae expressed as an absolute value was 0.49 and 0.27 ml/min
      respectively, which is lower than previously reported. Precision was 12.95 and
      16.33 and accuracy expressed as P30 was over 92.43% for CKD-EPI. There were no
      significant differences in GFR between the reference method and the estimation
      formulae. CONCLUSIONS: The performance of CKD-EPI and MDRD formulae can be
      significantly improved in the individual patient if the absolute values are used
      by removing the BSA normalization factor. Absolute estimated GFR by CKD-EPI is
      comparable to measured GFR, improving the performance of this formula in the
      assessment of individual kidney function, thus providing clinicians with an
      alternative to reference methods.

PMID- 24304465
TI  - Prostate-specific membrane antigen expression in tumor-associated vasculature of
      breast cancers.
AB  - Prostate-specific membrane antigen (PSMA) has been found to be expressed in the
      tumor-associated neovasculature of multiple solid tumor types including breast
      cancers. However, thus far, the number of cases studied from some tumor types has
      been limited. In this study, we set out to assess PSMA expression in the tumor
      associated vasculature associated with invasive breast carcinomas in a sizable
      cohort of patients. One hundred and six patients with AJCC stage 0-IV breast
      cancer were identified. Ninety-two of these patients had primary breast cancer
      [invasive breast carcinoma with or without co-existing ductal carcinoma in situ
      (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer
      metastases to the brain were identified. Immunohistochemical staining for PSMA
      and CD31 was performed on parallel representative tumor sections in each case.
      Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi
      quantitatively assessed based on two parameters: overall percent of endothelial
      positivity and staining intensity. PSMA expression for tumor-associated vascular
      endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if
      PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in
      >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the
      presence of vasculature in each case. Tumor-associated vasculature was PSMA
      positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast
      cancers metastatic to brain. PSMA was not detected in normal breast tissue or
      carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in
      normal breast tissue-associated vasculature. The 10-year overall survival was
      88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall
      survival (OS) was stratified based on PSMA score group, patients with PSMA scores
      of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p =
      0.12). When PSMA scores of 0 and 1 were compared with 2, there was a
      statistically significant difference in OS (96.0% vs 79.7%, respectively, p =
      0.05). Patients with a PSMA score of 2 had a significantly higher median tumor
      size compared with patients in the lower PSMA score groups (p = 0.04). Patients
      with higher nuclear grade were more likely to have a PSMA score of 2 compared
      with patients with lower nuclear grade (p < 0.0001). Patients with a PSMA score
      of 2 had a significantly higher median Ki-67 proliferation index compared with
      patients in the lower PSMA score groups (p < 0.0001). Patients with estrogen
      receptor (ER)-negative tumors were more likely to have a PSMA score of 2 compared
      with patients with ER-positive tumors (p < 0.0001). Patients with progesterone
      receptor (PR)-negative tumors were more likely to have a PSMA score of 2 compared
      with patients with PR-positive tumors (p = 0.03). No significant association was
      observed between PSMA score group status and lymph node involvement (p = 0.95).
      Too little variability was present in Human epidermal growth factor receptor-2
      (Her2/neu) amplified tumors to correlate with PSMA score group status. To date,
      this is the first detailed assessment of PSMA expression in the tumor-associated
      vasculature of primary and metastatic breast carcinomas. Further studies are
      needed to evaluate whether PSMA has diagnostic and/or potential therapeutic
      value. 

PMID- 24304466
TI  - Waist circumference and dual-energy X-ray absorptiometry measures of overall and
      central obesity are similarly associated with systemic oxidative stress in women.
AB  - Growing evidence suggests that overall and abdominal obesity might lead to
      oxidative stress (OxS), which, in turn, plays a key role in the pathogenesis of a
      wide spectrum of diseases. In this study, for the first time, we compared the
      correlations of indirect, i.e. anthropometric, and direct, by dual energy X-ray
      absorptiometry (DXA), measures of body fat with circulatory OxS markers in women.
      To address this issue, we assessed central and total body fat mass (FM) by DXA,
      and serum levels of advanced oxidation protein products (AOPP), thiols and
      hydroperoxides in 275 healthy women (age 21-65 years; body mass index [BMI] 21.1
      32.0 kg/m(2); waist circumference [WC] 60.1-109.9 cm). Among the markers
      considered in the study, only hydroperoxides levels, i.e. by-products of lipid
      peroxidation, were significantly (p < 0.05 for all) and positively correlated to
      body fat accumulation after controlling for confounding factors. In particular,
      this marker was found to be similarly associated with DXA-derived total FM, total
      FM % and trunk FM as well as with WC. Of note, hydroperoxides appeared to be
      correlated with abdominal but not with general obesity, as classified according
      to standard WC and BMI cut-offs, respectively. In conclusion, taken together our
      data demonstrated that, at least in women, the measurement of body FM by DXA has
      no advantage over the simpler and cheaper WC with regard to their associations
      with systemic OxS markers. Moreover, WC emerged as a superior potential predictor
      of OxS compared to the other most commonly used anthropometric measures
      (including BMI and waist to hip ratio).

PMID- 24304467
TI  - Phosphinite-iminopyridine iron catalysts for chemoselective alkene
      hydrosilylation.
AB  - A series of new pincer iron complexes with electron-donating phosphinite
      iminopyridine (PNN) ligands has been prepared and characterized. These iron
      compounds are efficient and selective catalysts for the anti-Markovnikov alkene
      hydrosilylation of primary, secondary, and tertiary silanes. More importantly,
      the system exhibits unprecedented functional group tolerance with reactive groups
      such as ketones, esters, and amides. Furthermore, the iron-catalyzed alkene
      hydrosilylation was successfully applied to the synthesis of a valuable
      insecticide, silafluofen. The electronic properties and structures of the iron
      complexes have been studied by spectroscopies and computational methods. Overall,
      the iron catalysts may provide a low-cost and environmentally benign alternative
      to currently employed precious metal systems for alkene hydrosilylation. 

PMID- 24304468
TI  - Synthesis and properties of the cyano complex of oxo-centered triruthenium core
      [Ru3(MU3-O)(MU-CH3COO)6(pyridine)2(CN)].
AB  - The preparation and properties of a new cyano complex containing the Ru3(MU3-O)
      core, [Ru3(MU3-O)(MU-CH3COO)6(py)2(CN)] (1; py = pyridine), are reported. Complex
      1 in CH2Cl2 showed intense absorption bands at 244, 334, and 662 nm,
      corresponding to a pi-pi* transition of the ligand, cluster-to-ligand charge
      transfer, and intracluster transitions, respectively. The cyclic voltammogram of
      1 in 0.1 M (n-Bu)4NPF6-CH2Cl2 showed redox waves for the processes
      Ru3(II,II,III)/Ru3(II,III,III), Ru3(II,III,III)/Ru3(III,III,III), and
      Ru3(III,III,III)/Ru3(III,III,IV) at E1/2 = -1.49, -0.26, and +1.03 V vs Ag/AgCl,
      respectively. The first two redox potentials are more negative by ca. 0.2 V in
      comparison with the corresponding potentials of [Ru3(MU3-O)(MU-CH3COO)6(py)3](+).
      This is in sharp contrast to the positive shifts of the corresponding waves of
      [Ru3(II,III,III)(MU3-O)(MU-CH3COO)6(py)2(CO)]. Density functional theory (DFT)
      calculations of [Ru3(II,III,III)(MU3-O)(MU-CH3COO)6(py)3], [Ru3(II,III,III)(MU3
      O)(MU-CH3COO)6(py)2(CN)](-), and [Ru3(II,III,III)(MU3-O)(MU-CH3COO)6(py)2(CO)]
      showed that the positive charge of the ruthenium is delocalized over the
      triruthenium cores of the first two and is localized as Ru(II)(CO){Ru(III)(py)}2
      in the CO complex. The calculations explain the difference in the pi interactions
      of the two ligands with the triruthenium cores. 

PMID- 24304469
TI  - Fungal functioning in a pine forest: evidence from a 15N-labeled global change
      experiment.
AB  - * We used natural and tracer nitrogen (N) isotopes in a Pinus taeda free air CO2
      enrichment (FACE) experiment to investigate functioning of ectomycorrhizal and
      saprotrophic fungi in N cycling. * Fungal sporocarps were sampled in 2004
      (natural abundance and (15) N tracer) and 2010 (tracer) and delta(15)N patterns
      were compared against litter and soil pools. * Ectomycorrhizal fungi with
      hydrophobic ectomycorrhizas (e.g. Cortinarius and Tricholoma) acquired N from the
      Oea horizon or deeper. Taxa with hydrophilic ectomycorrhizas acquired N from the
      Oi horizon (Russula and Lactarius) or deeper (Laccaria, Inocybe, and Amanita).
      (15)N enrichment patterns for Cortinarius and Amanita in 2010 did not correspond
      to any measured bulk pool, suggesting that a persistent pool of active organic N
      supplied these two taxa. Saprotrophic fungi could be separated into those
      colonizing pine cones (Baeospora), wood, litter (Oi), and soil (Ramariopsis),
      with delta(15)N of taxa reflecting substrate differences. (15)N enrichment
      between sources and sporocarps varied across taxa and contributed to delta(15)N
      patterns. * Natural abundance and (15)N tracers proved useful for tracking N from
      different depths into fungal taxa, generally corresponded to literature estimates
      of fungal activity within soil profiles, and provided new insights into
      interpreting natural abundance delta(15)N patterns.

PMID- 24304470
TI  - The GATA transcription factor/MTA-1 homolog egr-1 promotes longevity and stress
      resistance in Caenorhabditis elegans.
AB  - Aging is associated with a large number of both phenotypic and molecular changes,
      but for most of these, it is not known whether these changes are detrimental,
      neutral, or protective. We have identified a conserved Caenorhabditis elegans
      GATA transcription factor/MTA-1 homolog egr-1 (lin-40) that extends lifespan and
      promotes resistance to heat and UV stress when overexpressed. Expression of egr-1
      increases with age, suggesting that it may promote survival during normal aging.
      This increase in expression is dependent on the presence of the germline, raising
      the possibility that egr-1 expression is regulated by signals from the germline.
      In addition, loss of egr-1 suppresses the long lifespan of insulin receptor daf-2
      mutants. The DAF-16 FOXO transcription factor is required for the increased
      stress resistance of egr-1 overexpression mutants, and egr-1 is necessary for the
      proper regulation of sod-3 (a reporter for DAF-16 activity). These results
      indicate that egr-1 acts within the insulin signaling pathway. egr-1 can also
      activate the expression of its paralog egl-27, another factor known to extend
      lifespan and increase stress resistance, suggesting that the two genes act in a
      common program to promote survival. These results identify egr-1 as part of a
      longevity-promoting circuit that changes with age in a manner that is beneficial
      for the lifespan of the organism. 

PMID- 24304471
TI  - Differential marker expression by cultures rich in mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells have properties that make them amenable to
      therapeutic use. However, the acceptance of mesenchymal stem cells in clinical
      practice requires standardized techniques for their specific isolation. To date,
      there are no conclusive marker (s) for the exclusive isolation of mesenchymal
      stem cells. Our aim was to identify markers differentially expressed between
      mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared
      and contrasted the phenotype of tissue cultures in which mesenchymal stem cells
      are rich and rare. By initially assessing mesenchymal stem cell differentiation,
      we established that bone marrow and breast adipose cultures are rich in
      mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory
      tissue cultures contain rare mesenchymal stem cells. In particular, olfactory
      tissue cells represent non-stem cell mesenchymal cells. Subsequently, the
      phenotype of the tissue cultures were thoroughly assessed using immuno
      fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. RESULTS: Our
      analysis revealed that all tissue cultures, regardless of differentiation
      potential, demonstrated remarkably similar phenotypes. Importantly, it was also
      observed that common mesenchymal stem cell markers, and fibroblast-associated
      markers, do not discriminate between mesenchymal stem cell and non-stem cell
      mesenchymal cell cultures. Examination and comparison of the phenotypes of
      mesenchymal stem cell and non-stem cell mesenchymal cell cultures revealed three
      differentially expressed markers - CD24, CD108 and CD40. CONCLUSION: We indicate
      the importance of establishing differential marker expression between mesenchymal
      stem cells and non-stem cell mesenchymal cells in order to determine stem cell
      specific markers.

PMID- 24304473
TI  - Age and gender differences in the relationship between hepatitis C infection and
      all stages of Chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a worldwide health issue with heavy economic
      burden. Chronic hepatitis C virus (HCV) infection is a common cause of CKD, which
      can significantly impact the progression and mortality among patients with CKD.
      The prevalence of both illnesses is high in Taiwan. A multicentre and population
      based cross-sectional study including 24 642 subjects was conducted to explore
      the association of HCV infection with the prevalence and severity of CKD. The
      measurements of metabolic parameters, eGFR and CKD stages were compared between
      subjects with HCV seropositivity and seronegativity. The analyses of association
      between HCV infection with CKD stages and evaluation of potential risk factors of
      CKD were performed by gender and age (<= and >45 years). HCV-seropositive
      subjects accounted for 6.9% and had a significantly older age. The prevalence of
      CKD increased in those with HCV seropositivity (16.5%). Significantly higher
      prevalence of CKD stages >=3 in HCV-seropositive subjects was noticed (7.8%). Age
      (>45 year), male gender, alcohol drinking, hypertension, creatinine and HCV
      infection were the significant factors associated with the presence of CKD. HCV
      seropositivity was an independent risk factor of developing CKD and associated
      with an increased risk of having CKD of all stages. The higher prevalence of
      earlier stage of CKD warrants longitudinal studies with frequent testing on renal
      function and sufficient duration to determine the changes of eGFR over time.
      Implementation of effective treatment intervention is also required for these
      subjects to prevent the progression of CKD to late stages.

PMID- 24304472
TI  - alpha1 adrenoceptor activation by norepinephrine inhibits LPS-induced
      cardiomyocyte TNF-alpha production via modulating ERK1/2 and NF-kappaB pathway.
AB  - Cardiomyocyte tumour necrosis factor alpha (TNF-alpha) production contributes to
      myocardial depression during sepsis. This study was designed to observe the
      effect of norepinephrine (NE) on lipopolysaccharide (LPS)-induced cardiomyocyte
      TNF-alpha expression and to further investigate the underlying mechanisms in
      neonatal rat cardiomyocytes and endotoxaemic mice. In cultured neonatal rat
      cardiomyocytes, NE inhibited LPS-induced TNF-alpha production in a dose-dependent
      manner. alpha1- adrenoceptor (AR) antagonist (prazosin), but neither beta1- nor
      beta2-AR antagonist, abrogated the inhibitory effect of NE on LPS-stimulated TNF
      alpha production. Furthermore, phenylephrine (PE), an alpha1-AR agonist, also
      suppressed LPS-induced TNF-alpha production. NE inhibited p38 phosphorylation and
      NF-kappaB activation, but enhanced extracellular signal-regulated kinase 1/2
      (ERK1/2) phosphorylation and c-Fos expression in LPS-treated cardiomyocytes, all
      of which were reversed by prazosin pre-treatment. To determine whether ERK1/2
      regulates c-Fos expression, p38 phosphorylation, NF-kappaB activation and TNF
      alpha production, cardiomyocytes were also treated with U0126, a selective ERK1/2
      inhibitor. Treatment with U0126 reversed the effects of NE on c-Fos expression,
      p38 mitogen-activated protein kinase (MAPK) phosphorylation and TNF-alpha
      production, but not NF-kappaB activation in LPS-challenged cardiomyocytes. In
      addition, pre-treatment with SB202190, a p38 MAPK inhibitor, partly inhibited LPS
      induced TNF-alpha production in cardiomyocytes. In endotoxaemic mice, PE promoted
      myocardial ERK1/2 phosphorylation and c-Fos expression, inhibited p38
      phosphorylation and IkappaBalpha degradation, reduced myocardial TNF-alpha
      production and prevented LPS-provoked cardiac dysfunction. Altogether, these
      findings indicate that activation of alpha1-AR by NE suppresses LPS-induced
      cardiomyocyte TNF-alpha expression and improves cardiac dysfunction during
      endotoxaemia via promoting myocardial ERK phosphorylation and suppressing NF
      kappaB activation.

PMID- 24304474
TI  - Methylphenidate treatment of attention deficit  hyperactivity disorder in young
      people  with learning disability and difficult-to-treat  epilepsy: evidence of
      clinical benefit.
AB  - PURPOSE: To establish the efficacy and safety of methylphenidate (MPH) treatment
      for attention deficit hyperactivity disorder (ADHD) in a group of children and
      young people with learning disability and severe epilepsy. METHODS: This
      retrospective study systematically reviewed the case notes of all patients
      treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center
      between 1998 and 2005. Treatment efficacy was ascertained using clinical global
      impressions (CGI) scores, and safety was indexed by instances of >25% increase in
      monthly seizure count within 3 months of starting MPH. KEY FINDINGS: Eighteen
      (18) patients were identified with refractory epilepsies (14 generalized, 4
      focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was
      diagnosed at a median age of 11.5 years (range 6-18 years). With use of a
      combination of a behavioral management program and MPH 0.3-1 mg/kg/day, ADHD
      symptoms improved in 61% of patients (11/18; type A intraclass correlation
      coefficient of CGI 0.85, 95% confidence interval [CI] 0.69-0.94). Daily MPH dose,
      epilepsy variables, and psychiatric comorbidity did not relate to treatment
      response across the sample. MPH adverse effects led to treatment cessation in
      three patients (dysphoria in two, anxiety in one). There was no statistical
      evidence for a deterioration of seizure control in this group with the use of
      MPH. SIGNIFICANCE: Methylphenidate with behavioral management was associated with
      benefit in the management of ADHD in more than half of a group of children with
      severe epilepsy and additional cognitive impairments. Eighteen percent had
      significant side effects but no attributable increase in seizures.
      Methylphenidate is useful in this group and is likely to be under employed.

PMID- 24304475
TI  - A case report of transfusion-transmitted Plasmodium malariae from an asymptomatic
      non-immune traveller.
AB  - BACKGROUND: The incidence of transfusion-transmitted malaria is very low in non
      endemic countries due to strict donor selection. The optimal strategy to mitigate
      the risk of transfusion-transmitted malaria in non-endemic countries without
      unnecessary exclusion of blood donations is, however, still debated and
      asymptomatic carriers of Plasmodium species may still be qualified to donate
      blood for transfusion purposes. CASE DESCRIPTION: In April 2011, a 59-year-old
      Dutch woman with spiking fevers for four days was diagnosed with a Plasmodium
      malariae infection. The patient had never been abroad, but nine weeks before, she
      had received red blood cell transfusion for anaemia. The presumptive diagnosis of
      transfusion-transmitted quartan malaria was made and subsequently confirmed by
      retrospective PCR analysis of donor blood samples. The donor was a 36-year-old
      Dutch male who started donating blood in May 2006. His travel history outside
      Europe included a trip to Kenya, Tanzania and Zanzibar in 2005, to Thailand in
      2006 and to Costa Rica in 2007. He only used malaria prophylaxis during his
      travel to Africa. The donor did not show any abnormalities upon physical
      examination in 2011, while laboratory examination demonstrated a thrombocytopenia
      of 126 * 109/L as the sole abnormal finding since 2007. Thick blood smear
      analysis and the Plasmodium PCR confirmed an ongoing subclinical P. malariae
      infection. Chloroquine therapy was started, after which the infection cleared and
      thrombocyte count normalized. Fourteen other recipients who received red blood
      cells from the involved donor were traced. None of them developed malaria
      symptoms. DISCUSSION: This case demonstrates that P. malariae infections in non
      immune travellers may occur without symptoms and persist subclinically for years.
      In addition, this case shows that these infections pose a threat to transfusion
      safety when subclinically infected persons donate blood after their return in a
      non-endemic malaria region.Since thrombocytopenia was the only abnormality
      associated with the subclinical malaria infection in the donor, this case
      illustrates that an unexplained low platelet count after a visit to malaria
      endemic countries may be an indicator for asymptomatic malaria even when caused
      by non-falciparum Plasmodium species.

PMID- 24304476
TI  - Changes in geometric configuration and biomechanical parameters of a rapidly
      growing abdominal aortic aneurysm may provide insight in aneurysms natural
      history and rupture risk.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are currently being treated based on
      the maximum diameter criterion which has often been proven insufficient to
      determine rupture risk in case of every AAA. We analyzed a rare case of an AAA
      which presented an extremely fast growth focusing on biomechanical determinants
      that may indicate a high risk profile. The examination of such a case is expected
      to motivate future research towards patient-specific rupture risk estimations.
      METHODS: An initially small AAA (maximum diameter: 4.5 cm) was followed-up and
      presented a growth of 1 cm in only 6-months of surveillance becoming suitable for
      surgical repair. Changes of morphometric characteristics regarding AAA, thrombus
      and lumen volumes, cross-sectional areas, thrombus maximum thickness and
      eccentricity, and maximum centerline curvature were recorded. Moreover
      biomechanical variables concerning Peak Wall Stress, AAA surface area exposed to
      high stress and redistribution of stress during follow-up were also assessed.
      RESULTS: Total aneurysm volume increased from 85 to 120 ml which regarded
      thrombus deposition since lumen volume remained stable. Thrombus deposition was
      eccentric regarding anterior AAA segment while its thickness increased from 0.3
      cm to 1.6 cm. Moreover there was an anterior bulging over time as depicted by an
      increase in maximum centerline curvature from 0.4 cm-1 to 0.5 cm-1. Peak Wall
      Stress (PWS) exerted on aneurysm wall did not change significantly over time,
      slightly decreasing from 22 N/cm2 to 21 N/cm2. At the same time the area under
      high wall stress remained practically constant (9.9 cm2 at initial vs 9.7 cm2 at
      final examination) but there was a marked redistribution of wall stress against
      the posterior aneurysmal wall over time. CONCLUSION: Aneurysm area under high
      stress and redistribution of stress against the posterior wall due to changes in
      geometric configuration and thrombus deposition over time may have implications
      to aneurysms natural history and rupture risk.

PMID- 24304477
TI  - Caterpillar attack triggers accumulation of the toxic maize protein RIP2.
AB  - Some plant-derived anti-herbivore defensive proteins are induced by insect
      feeding, resist digestion in the caterpillar gut and are eliminated in the frass.
      We have identified several maize proteins in fall armyworm (Spodoptera
      frugiperda) frass that potentially play a role in herbivore defense. Furthermore,
      the toxicity of one of these proteins, ribosome-inactivating protein 2 (RIP2),
      was assessed and factors regulating its accumulation were determined. To
      understand factors regulating RIP2 protein accumulation, maize (Zea mays) plants
      were infested with fall armyworm larvae or treated with exogenous hormones. The
      toxicity of recombinant RIP2 protein against fall armyworm was tested. The
      results show that RIP2 protein is synthesized as an inactive proenzyme that can
      be processed in the caterpillar gut. Also, caterpillar feeding, but not
      mechanical wounding, induced foliar RIP2 protein accumulation. Quantitative real
      time PCR indicated that RIP2 transcripts were rapidly induced (1 h) and
      immunoblot analysis indicated that RIP2 protein accumulated soon after attack and
      was present in the leaf for up to 4 d after caterpillar removal. Several
      phytohormones, including methyl jasmonate, ethylene, and abscisic acid, regulated
      RIP2 protein expression. Furthermore, bioassays of purified recombinant RIP2
      protein against fall armyworm significantly retarded caterpillar growth. We
      conclude that the toxic protein RIP2 is induced by caterpillar feeding and is one
      of a potential suite of proteins that defend maize against chewing herbivores. 

PMID- 24304478
TI  - Effect of weight-loss program using self-weighing twice a day and feedback in
      overweight and obese subject: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of self-weighing twice a day with a
      supportive program installed on a body composition monitor in overweight adults.
      SUBJECTS: Sixty adults with BMI > 24 kg/m(2) were randomly assigned to either a
      group that weighed themselves once per day (group 1, n = 30) or a group that
      weighed themselves twice per day (group 2, n = 30). INTERVENTION: Group 1 was
      instructed to self-weigh at the same time once per day and group 2 was instructed
      to self-weigh immediately after waking up in the morning and immediately before
      going to bed every day for twelve weeks. In addition, participants in group 2 was
      received the daily target setting during morning weighing and the difference
      between the measured weight and the target weight during bedtime weighing.
      RESULTS: Average weight reduction in group 1 was significantly lower than that in
      group 2 (1.0 +/- 1.4 kg vs. 2.7 +/- 2.1 kg, p < 0.05). The proportion of
      participants who lost >= 5% of their pre-program weight in group 2 was
      significantly higher than that in group 1 (28.6% vs. 3.6%, p < 0.05). CONCLUSION:
      A self-weighing twice per day plus daily target setting and feedback is more
      effective in promoting weight loss than once-daily self-measurement.

PMID- 24304479
TI  - Predictors of initial weight loss after gastric bypass surgery in twelve Veterans
      Affairs Medical Centers.
AB  - The objective of this study was to identify determinants of significant weight
      loss one year after gastric bypass surgery among United States veterans. Using
      data from the Veterans Affairs (VA) Surgical Quality Improvement Program, we
      identified 516 veterans who had gastric bypass surgery (24% laparoscopic) in one
      of twelve VA bariatric centers in 2000-2006 and one or more postoperative weight
      measures. The probability of losing 30% or more of baseline weight at one year
      was estimated via logistic regression, examining the following potential
      predictor variables: age, gender, race, marital status, body mass index (BMI),
      American Society of Anesthesiologists class, comorbidity burden, smoking status,
      diabetes medications taken and surgical procedure (open or laparoscopic). The 516
      cases had a mean BMI of 49 kg/m(2), mean age of 51.5 years, 74% were male, 77%
      were Caucasian, and 55% were married. The predicted mean weight loss was 76 (95%
      CI: 73-79) pounds (22%) at six months and 109 (95% CI: 104-114) pounds (32%) at
      one-year. Based upon estimated individual trajectories of 370 patients with
      adequate follow-up data, 58% of the sample lost 30% or more of their baseline
      weight at one year; and <1% lost <10% of their baseline weight at 1 year. In the
      logistic regression, patients were more likely to lose 30% or more of their
      baseline weight if they were female (odds ratio (OR) = 2.5, p < 0.01) or
      Caucasian (OR = 2.3, p < 0.01). We conclude that gastric bypass surgery yields
      significant weight loss for most patients in Veterans Affairs Medical Centers,
      but is particularly effective for female and Caucasian patients.

PMID- 24304480
TI  - Overweight/obesity and weight-related treatment among patients in U.S. federally
      supported health centers.
AB  - BACKGROUND: We obtained the prevalence of overweight/obesity, weight-loss
      attempts, and weight-related counseling and treatment among U.S. adults who
      sought care in federally funded community health centers. We investigated whether
      racial/ethnic and gender disparities existed for these measures. METHODS: Data
      came from the 2009 Health Center Patient Survey. Measures included body mass
      index (BMI), self-perceived weight, weight-loss attempts, being told of a weight
      problem, receipt of weight-related counseling, nutritionist referrals, weight
      loss prescriptions, and cholesterol checks. We conducted bivariate analyses to
      determine distributions by race/ethnicity and gender, then ran logistic
      regressions to examine the effects of several sociodemographic factors on weight
      loss attempts and on being told of a weight problem. RESULTS: Overall, 76% of
      adult patients seen in health centers were overweight or obese (BMI >= 25.0
      kg/m(2)); 55% of overweight patients, and 87% of obese patients correctly
      perceived themselves as overweight. There were no racial/ethnic differences in
      BMI categories or self-perceptions of weight. Females were more likely than males
      to be obese and also more likely to perceive themselves as overweight. About 60%
      of overweight/obese patients reported trying to lose weight in the past year.
      There were no racial/ethnic disparities favoring non-Hispanic White patients in
      weight-related treatment. Women were more likely than men to receive referrals to
      a nutritionist or weight-loss prescriptions. Overweight/obese patients had higher
      adjusted odds of a past-year weight-loss attempt if they perceived themselves as
      overweight (OR = 3.30, p < 0.0001), were female (OR = 1.95, p < 0.05), African
      American (OR = 3.34, p < 0.05), or Hispanic/Latino (OR = 2.14, p < 0.05).
      Overweight/obese patients had higher odds of being told they had a weight problem
      if they were Hispanic/Latino (OR = 2.56, p < 0.05) or if they had two or more
      chronic conditions (OR = 2.77, p < 0.01). CONCLUSIONS: Patients seen in community
      health centers have high rates of overweight and obesity, even higher than the
      general U.S. population. Efforts to address weight problems during primary care
      visits are needed to reduce the burden of obesity and its sequellae among health
      center patients.

PMID- 24304481
TI  - Gender differences in lifestyle determinants of overweight prevalence in a sample
      of Southern European children.
AB  - OBJECTIVE: The association between sleep duration, extracurricular sport, screen
      based activities and dietary variables with prevalence of overweight in middle
      childhood, regarding gender differences, was assessed. METHODS: Cross-sectional
      study involving 2814 children (age 6-12 years). Measured weight and height and
      reported lifestyle variables were obtained by health professionals previously
      trained. Univariate and multivariate logistic regression analyses were performed
      to examine the associations between variables and the likelihood of being
      overweight. RESULTS: Prevalence of overweight (including obesity) was 31.9% in
      boys and 30.4% in girls. In boys, engaging >= 3 h/week in sports activities (OR
      0.7, 95% CI 0.5-0.9), eating daily breakfast (OR 0.6, 95% CI 0.4-0.9) and
      consuming >= 2 fruits/day (OR 0.8, 95% CI 0.6-0.9) were independent protective
      factors against overweight, whereas children consuming fast food weekly and
      sweets daily were estimated to be 30% and 40%, respectively, more likely to be
      overweight. Only buns consumption resulted associated with overweight in girls
      (OR 1.3, 95% CI 1.1-1.7). CONCLUSIONS: Prevalence of overweight in a sample of
      Southern European children is high and underlines gender differences in lifestyle
      determinants. Engaging in extracurricular sport, promoting daily breakfast,
      adequate fruit consumption and reducing high energy-dense foods, should be
      encouraged in boys, whereas further investigation on girls behaviours would be
      valuable.

PMID- 24304482
TI  - BMI percentile curves for Japanese men and women aged 20-79 years who underwent a
      health check-up in 1980 and 2005.
AB  - OBJECTIVE: To establish body mass index (BMI) percentile curves for adults and to
      compare these in 1980 with those in 2005 among Japanese men and women. METHODS:
      Participants included 8080 community residents aged 20-79 years who had a health
      check-up in 1980 and 5616 community residents aged 20-79 years who had a health
      check-up in 2005. Sex-specific percentile curves for BMI were constructed using
      the LMS method. We presented the 3rd, 5th, 15th, 25th, 50th, 75th, 85th, 95th,
      and 97th percentile curves. RESULTS: From 1980 to 2005, the BMI percentile values
      of men increased, especially the 95th and 97th percentile values in men aged 20
      39 years. The BMI distribution of young men in 2005 was wider than that in 1980.
      From 1980 to 2005, the 50th percentile values of women in 2005 were lower than
      those in 1980. However, the 95th percentile values of women increased among women
      aged less than 50 years. CONCLUSION: We were able to confirm the existence of BMI
      percentile values depending on date, age, and sex by establishing BMI percentile
      curves.

PMID- 24304483
TI  - Predictors of food and physical activity patterns among schoolchildren in the
      region of Sousse, Tunisia.
AB  - AIM: To facilitate the improvement of future interventions, it's important to
      know the determinants of healthy behaviors. Our aim was to determine the
      predictors of healthy habits in a school based intervention study to promote
      healthy diet and physical activity among schoolchildren in the region of Sousse,
      Tunisia. METHODS: It was a quasi-experimental intervention study with two groups:
      control and intervention group with pre-post evaluation of nutrition and physical
      activity intention and behavior in each group. The target population was composed
      with students aged 12-16 years schooled in colleges of Sousse in Tunisia. To
      evaluate the intervention, a sampling was used to include 2200 students who
      participated to the questionnaire. All the students of intervention group
      received a standardized program with information about healthy nutrition and
      physical activity. An Arabic pre-tested and auto-administered questionnaire was
      used to assess nutrition and physical activity intention and behavior before and
      after the intervention. RESULTS: The intervention group's posttest knowledge and
      behavioral intention were significantly higher than the control group's posttest.
      No significant differences occurred in posttest attitudes between the control and
      intervention groups. A multivariate logistic regression models were used to
      identify the predictors of students' "healthy behavior". CONCLUSION: This school
      based intervention improved eating and physical activity intentions and behaviors
      among schoolchildren. "Healthy behaviors' were determined by age, father's
      profession and home characteristics. This finding could direct future
      interventions to disadvantaged categories.

PMID- 24304484
TI  - Apolipoprotein A-V level may contribute to the development of obesity-associated
      dyslipidemia.
AB  - AIM: In a mice study, insulin suppressed apolipoprotein A-V (apoA-V) gene
      expression in a dose dependent manner. Thus, we investigated the association
      between apoA-V levels and dyslipidemias in obese children with hyperinsulinemia.
      METHODS: The subjects were 17 obese children (15 male, 2 female) aged 11.8 +/-
      2.4 years. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC),
      triglyceride (TG), apoA-V and insulin levels were determined. RESULTS: Obese
      children with hyperinsulinemia had greater percent overweight, higher TG level,
      lower HDLC level and lower apoA-V level than those without hyperinsulinemia. In
      simple regression analysis, apoA-V level correlated negatively with TG (r = 
      0.613, p = 0.0152) and insulin levels (r = -0.566, p = 0.0279), and positively
      correlated with HDLC (r = 0.811, p = 0.0002). In stepwise regression analysis,
      insulin level emerged as the independent determinant of TG level after apoA-V
      level was taken into account, whereas apoA-V emerged as the independent
      determinant of HDLC level after adjusting for insulin level. CONCLUSIONS: Insulin
      may be a potent regulator of serum apoA-V level in obesity, and apoA-V level may
      partly contribute to the development of obesity-associated dyslipidemia.

PMID- 24304485
TI  - Client satisfaction and weight loss outcomes of student centred dietetic
      outpatient clinics.
AB  - AIM: Evaluation of health care services and providers is essential in determining
      effectiveness and quality. The aim of this study was to assess the client
      satisfaction and weight loss outcomes of student focussed dietetic outpatient
      weight loss clinics. METHODS: The outpatient clinics were conducted by the
      University as part of student education. Sixty-one clients attended a new
      appointment during 2008. Anthropometric and demographic details were extracted
      from clients' clinic records. Clients were mailed a 30-item satisfaction survey
      adapted from an existing instrument. RESULTS: Twenty-six surveys were returned
      (43% response rate). Respondents were less likely to be satisfied with
      appointment wait times and availability of parking (65%, 70%, respectively)
      compared with other factors. Dietitians were seen as polite and courteous, and
      the presence of students did not lessen the attention from the dietitian. Mean
      (SD) weight change was -3.3 (3.2) kg over 12 months (P < 0.05, n = 20).
      CONCLUSION: It was found that clients were satisfied with services and while
      statistically significant weight loss was achieved, results did not reach the
      clinically significant weight loss of 5% of initial weight.

PMID- 24304486
TI  - Ventricular remodelling in rabbits with sustained high-fat diet.
AB  - AIM: Excess weight gain and obesity are one of the most serious health problems
      in the western societies. These conditions enhance risk of cardiac disease and
      have been linked with increased prevalence for cardiac arrhythmias and sudden
      death. Our goal was to study the ventricular remodelling occurring in rabbits fed
      with high-fat diet (HFD) and its potential arrhythmogenic mechanisms. METHODS: We
      used 15 NZW rabbits that were randomly assigned to a control (n = 7) or HFD group
      (n = 8) for 18 weeks. In vivo studies included blood glucose,
      electrocardiographic, and echocardiographic measurements. Optical mapping was
      performed in Langendorff-perfused isolated hearts. RESULTS: Body weight (3.69 +/-
      0.31 vs. 2.94 +/- 0.18 kg, P < 0.001) and blood glucose levels (230 +/- 61 vs.
      141 +/- 14 mg dL(-1) , P < 0.05) were higher in the HFD group vs. controls. The
      rate-corrected QT interval and its dispersion were increased in HFD rabbits vs.
      controls (169 +/- 10 vs. 146 +/- 13 ms and 37 +/- 11 vs. 9 +/- 2 ms,
      respectively; P < 0.05). Echocardiographic analysis showed morphological and
      functional alterations in HFD rabbits indicative of left ventricle (LV)
      hypertrophy. Isolated heart studies revealed no changes in repolarization and
      propagation properties under conditions of normal extracellular K(+) , suggesting
      that extrinsic factors could underlie those electrocardiographic modifications.
      There were no differences in the dynamics of ventricular fibrillation (frequency,
      wave breaks) in the presence of isoproterenol. However, HFD rabbits showed a
      small reduction in action potential duration and an increased incidence of
      arrhythmias during hyperkalaemia. CONCLUSION: High-fat feeding during 18 weeks in
      rabbits induced a type II diabetes phenotype, LV hypertrophy, abnormalities in
      repolarization and susceptibility to arrhythmias during hyperkalaemia.

PMID- 24304488
TI  - Association between multiple sclerosis and epilepsy: large population-based
      record-linkage studies.
AB  - BACKGROUND: Multiple sclerosis (MS) and epilepsy are both fairly common and it
      follows that they may sometimes occur together in the same people by chance. We
      sought to determine whether hospitalisation for MS and hospitalisation for
      epilepsy occur together more often than expected by chance alone. METHODS: We
      analysed two datasets of linked statistical hospital admission records covering
      the Oxford Record Linkage Study area (ORLS, 1963-1998) and all England (1999
      2011). In each, we calculated the rate of occurrence of hospital admission for
      epilepsy in people after admission for MS, compared with equivalent rates in a
      control cohort, and expressed the results as a relative risk (RR). RESULTS: The
      RR for hospital admission for epilepsy following an admission for MS was
      significantly high at 4.1 (95% confidence interval 3.1-5.3) in the ORLS and 3.3
      (95% CI 3.1-3.4) in the all-England cohort. The RR for a first recorded admission
      for epilepsy 10 years and more after first recorded admission for MS was 4.7 (2.8
      7.3) in ORLS and 3.9 (3.1-4.9) in the national cohort. The RR for the converse-MS
      following hospitalisation for epilepsy-was 2.5 (95% CI 1.7-3.5) in the ORLS and
      1.9 (95% CI 1.8-2.1) in the English dataset. CONCLUSIONS: MS and epilepsy occur
      together more commonly than by chance. One possible explanation is that an MS
      lesion acts as a focus of an epileptic seizure; but other possibilities are
      discussed. Clinicians should be aware of the risk of epilepsy in people with MS.
      The findings may also suggest clues for researchers in developing hypotheses
      about underlying mechanisms for the two conditions.

PMID- 24304487
TI  - Genome-wide DNA methylation changes with age in disease-free human skeletal
      muscle.
AB  - A decline in skeletal muscle mass and function with aging is well recognized, but
      remains poorly characterized at the molecular level. Here, we report for the
      first time a genome-wide study of DNA methylation dynamics in skeletal muscle of
      healthy male individuals during normal human aging. We predominantly observed
      hypermethylation throughout the genome within the aged group as compared to the
      young subjects. Differentially methylated CpG (dmCpG) nucleotides tend to arise
      intragenically and are underrepresented in promoters and are overrepresented in
      the middle and 3' end of genes. The intragenic methylation changes are
      overrepresented in genes that guide the formation of the junction of the motor
      neuron and myofibers. We report a low level of correlation of gene expression
      from previous studies of aged muscle with our current analysis of DNA methylation
      status. For those genes that had both changes in methylation and gene expression
      with age, we observed a reverse correlation, with the exception of intragenic
      hypermethylated genes that were correlated with an increased gene expression. We
      suggest that a minimal number of dmCpG sites or select sites are required to be
      altered in order to correlate with gene expression changes. Finally, we
      identified 500 dmCpG sites that perform well in discriminating young from old
      samples. Our findings highlight epigenetic links between aging postmitotic
      skeletal muscle and DNA methylation. 

PMID- 24304489
TI  - Molecular analysis of the diets of snakes: changes in prey exploitation during
      development of the rare smooth snake Coronella austriaca.
AB  - Reptiles are declining in many parts of the world, mainly due to habitat loss and
      environmental change. A major factor in this is availability of suitable food.
      For many animals, dietary requirements shift during developmental stages and a
      habitat will only be suitable for conserving a species if it supports all stages.
      Conventional methods for establishing diet often rely on visual recognition of
      morphologically identifiable features of prey in faeces, regurgitation or stomach
      contents, which suffer from biases and poor resolution of taxa. DNA-based
      techniques facilitate noninvasive analysis of diet from faeces without these
      constraints. We tested the hypothesis that diet changes during growth stages of
      smooth snakes (Coronella austriaca), which have a highly restricted distribution
      in the UK but are widespread in continental Europe. Small numbers of the
      sympatric grass snake (Natrix natrix) were analysed for comparison. Faecal
      samples were collected from snakes and prey DNA analysed using PCR, targeting
      amphibians, reptiles, mammals and invertebrates. Over 85% of smooth snakes were
      found to have eaten reptiles and 28% had eaten mammals. Predation on mammals
      increased with age and was entirely absent among juveniles and subadults.
      Predation on reptiles did not change ontogenetically. Smooth snakes may,
      therefore, be restricted to areas of sufficiently high reptile densities to
      support young snakes. 

PMID- 24304490
TI  - The effect of a single Finnish sauna bath after aerobic exercise on the oxidative
      status in healthy men.
AB  - BACKGROUND: The aim of this study was to determine the effect of Finnish sauna as
      a regeneration method post-exercise on the oxidant-antioxidant balance in healthy
      men. MATERIAL: 43 men aged 24.0 +/- 4.3 years performed a 30-min aerobic exercise
      on a cycle ergometer and rested for 39 min at a room temperature (Day 1; 20
      degrees C) or in a sauna for post-workout recovery (Day 2; 90 degrees C, air
      humidity 10%). Blood was taken 3 times during both study days: Before the
      exercise (baseline), 20 and 40 min after the recovery. Methods. The activity of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) was
      determined in the subjects' erythrocytes. The concentration of thiobarbituric
      acid reactive substances (TBARS) was measured both in plasma (TBARSpl) and in the
      erythrocytes (TBARSer). RESULTS: A 12.7% increase in the TBARSpl concentration
      versus the baseline was observed 40 min after the Finnish sauna (p < 0.01). The
      CAT activity observed 20 and 40 min after the sauna was also found higher by 8.1%
      and 8.9%, respectively, in comparison with the baseline (p < 0.05). In turn, the
      TBARSer concentration was lower by 17.5% 40 min after the recovery in the sauna,
      as compared with the TBARSer concentration 40 min after the recovery at the room
      temperature (p < 0.05). CONCLUSIONS: A single Finnish sauna bath as a source of
      free radicals per se is able to reduce oxidative stress induced by a 30-min
      aerobic exercise in healthy men.

PMID- 24304491
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of
      contrast-induced nephropathy after percutaneous coronary intervention.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) occurs in up to 13% of
      patients undergoing percutaneous coronary intervention (PCI). Neutrophil
      gelatinase-associated lipocalin (NGAL) is an early biomarker for renal
      impairment. We investigated whether increased urinary NGAL concentrations were
      predictive of CI-AKI within 2 days after PCI or of a higher re-hospitalization
      rate within 9 months. METHODS: Consecutive patients (n = 128), with stable
      coronary heart disease and eGFR >= 30 mL/min/1.73 m(2), undergoing PCI were
      included. Venous serum samples for measurement of creatinine, blood urea
      nitrogen, and cystatin C and urine samples for NGAL measurement were collected 4
      hours and 1 and 2 days after contrast medium application. Patients were followed
      over 9 months to determine clinical endpoints. RESULTS: CI-AKI was observed in 14
      patients (10.9%) after PCI. NGAL concentrations before PCI were significantly
      higher in patients with subsequent CI-AKI (19.8 ng/mL [14.4-35.8] vs. 11.6 ng/mL
      [5.6-28.2]; p = 0.04). There was no significant difference in NGAL concentrations
      4 h after PCI between patients with and without CI-AKI. One day after PCI, NGAL
      concentrations were significant higher in patients developing CI-AKI (100.1 ng/mL
      [41.5-129.2] vs. 16.6 ng/mL [9.1-28.1]; p < 0.001). Compared to common
      biomarkers, NGAL best predicted CI-AKI (AUC 0.939 [95% CI 0.89-0.99; p < 0.001]).
      The re-hospitalization rate due to progressive renal insufficiency within 9
      months was higher in the group with CI-AKI than the group without (4 [28.6%] vs.
      4 [3.5%], p < 0.01). CONCLUSION: Urinary NGAL is a biomarker for predicting CI
      AKI when measured 1 day after PCI.

PMID- 24304492
TI  - The relationship between high-sensitive troponin T, neutrophil lymphocyte ratio
      and SYNTAX Score.
AB  - AIM: Cardiac troponins are the most preferred biomarkers in the evaluation of
      acute coronary syndromes (ACS). The aim of our study was to examine the
      association between high sensitive troponin T (hs-TnT), and neutrophil to
      lymphocyte ratio (NLR) and the complexity of ACS assessed by SYNTAX Score.
      METHODS AND RESULTS: 287 patients who underwent coronary angiography were studied
      (215 male, mean age 62.0 +/- 12.7 years). 133 patients were ST elevation
      myocardial infarction (STEMI), 154 patients were non-ST elevation (NSTE) ACS .
      The patients are divided to tertiles according to SYNTAX Score; SYNTAX Score <=
      22 (n = 122) 22 < SYNTAX Score <= 32 (n = 120), and SYNTAX Score > 32 (n = 45).
      NLR was significantly correlated with SYNTAX Score in both STEMI and NSTE-ACS
      groups (r = 0.254, p = 0.003, r = 0.419 p < 0.001). Multiple linear regression
      analysis showed NLR predicted the angiographic severity of ACS assessed by SYNTAX
      Score in two groups (beta = 0.231, p = 0.004; beta = 0.232, p = 0.003). Hs-TnT
      was significantly correlated with SYNTAX Score in two groups (r = 0.327, p <
      0.001; r = 0.430, p < 0.001). Multiple linear regression analysis showed hs-TnT
      was independent predictor of SYNTAX Score in STEMI and NSTE-ACS patients (beta =
      0.292, p < 0.001; beta = 0.317, p < 0.001). CONCLUSION: Hs-TnT and NLR were
      significantly correlated with angiographic severity of ACS assessed by SYNTAX
      Score.

PMID- 24304494
TI  - Biological effects of blocking blue and other visible light on the mouse retina.
AB  - BACKGROUND: To elucidate the biological effects of blocking fluorescent light on
      the retina using specific blocking materials. METHODS: Seven- to 8-week-old
      BALB/c mice were divided into three groups and placed in one of the three boxes:
      one blocked ultraviolet and violet wavelengths of light (violet blockade), one
      blocked ultraviolet, violet, blue and some other visible wavelengths (blue-plus
      blockade), and one allowed most visible light to pass through (control). They
      were then exposed to a white fluorescent lamp for 1 h at 5.65E-05 mW/cm(2) /s.
      After treatment, the electroretinogram, retinal outer nuclear layer thickness and
      retinal outer segment length were measured. In addition, retinal apoptotic cells
      were quantified by TdT-mediated dUTP nick-end labelling assay and c-Fos messenger
      RNA, and protein levels were measured by real-time reverse-transcription
      polymerase chain reaction and immunoblot analyses, respectively. RESULTS: The
      blue-plus blockade group retained a significantly better electroretinogram
      response following light exposure than the control or violet blockade groups. The
      blue-plus blockade group also exhibited greater outer nuclear layer thickness and
      greater outer-segment length, and fewer apoptotic cells after light exposure than
      the other groups. The c-Fos messenger RNA and protein levels were substantially
      reduced in the blue-plus blockade group and reduced to a lesser extent in the
      violet blockade group. CONCLUSIONS: The blockade of blue plus additional visible
      wavelengths of light was most effective in protecting the retina from light
      induced damage. The blockade of violet light alone was also effective in reducing
      intracellular molecular responses, but these effects were not sufficient for
      attenuating retinal degeneration.

PMID- 24304493
TI  - The precise timeline of transcriptional regulation reveals causation in mouse
      somitogenesis network.
AB  - BACKGROUND: In vertebrate development, the segmental pattern of the body axis is
      established as somites, masses of mesoderm distributed along the two sides of the
      neural tube, are formed sequentially in the anterior-posterior axis. This
      mechanism depends on waves of gene expression associated with the Notch, Fgf and
      Wnt pathways. The underlying transcriptional regulation has been studied by whole
      transcriptome mRNA profiling; however, interpretation of the results is limited
      by poor resolution, noisy data, small sample size and by the absence of a wall
      clock to assign exact time for recorded points. RESULTS: We present a method of
      Maximum Entropy deconvolution in both space and time and apply it to extract,
      from microarray timecourse data, the full spatiotemporal expression profiles of
      genes involved in mouse somitogenesis. For regulated genes, we have reconstructed
      the temporal profiles and determined the timing of expression peaks along the
      somite cycle to a single-minute resolution. Our results also indicate the
      presence of a new class of genes (including Raf1 and Hes7) with two peaks of
      activity in two distinct phases of the somite cycle. We demonstrate that the
      timeline of gene expression precisely reflects their functions in the biochemical
      pathways and the direction of causation in the regulatory networks. CONCLUSIONS:
      By applying a novel framework for data analysis, we have shown a striking
      correspondence between gene expression times and their interactions and
      regulations during somitogenesis. These results prove the key role of finely
      tuned transcriptional regulation in the process. The presented method can be
      readily applied to studying somite formation in other datasets and species, and
      to other spatiotemporal processes.

PMID- 24304495
TI  - Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells.
AB  - Avoidance of long-term immunosuppression is a desired goal in organ
      transplantation. Mixed chimerism offers a promising approach to tolerance
      induction, and we have aimed to develop low-toxicity, nonimmunodepleting
      approaches to achieve this outcome. In a mouse model achieving fully MHC
      mismatched allogeneic bone marrow engraftment with minimal conditioning (3 Gy
      total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone
      marrow cells), CD4 T cells in the recipient are required to promote tolerance of
      preexisting alloreactive recipient CD8 T cells and thereby permit chimerism
      induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject
      MHC Class I-deficient and Class I/Class II-deficient marrow in a CD8 T cell
      dependent manner. This rejection is specific for donor alloantigens, since
      recipient hematopoiesis is not affected by donor marrow rejection and MHC Class I
      deficient bone marrow that is syngeneic to the recipient is not rejected.
      Recipient CD8 T cells are activated and develop cytotoxicity against MHC Class I
      deficient donor cells in association with rejection. These data implicate a novel
      CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells
      indirectly activated by donor alloantigens promote direct killing, in a T cell
      receptor-independent manner, of Class I-deficient donor cells.

PMID- 24304496
TI  - Mitogen-activated protein kinase-activated protein kinase 2 mediates apoptosis
      during lung vascular permeability by regulating movement of cleaved caspase 3.
AB  - Apoptosis is a key pathologic feature in acute lung injury. Animal studies have
      demonstrated that pathways regulating apoptosis are necessary in the development
      of acute lung injury, and that activation of p38 mitogen-activated protein kinase
      (MAPK) is linked to the initiation of the apoptotic cascade. In this study, we
      assessed the role of the MAPK-activated protein kinase (MK) 2, one of p38 MAPK's
      immediate downstream effectors, in the development of apoptosis in an animal
      model of LPS-induced pulmonary vascular permeability. Our results indicate that
      wild-type (WT) mice exposed to LPS demonstrate increased apoptosis, as evidenced
      by cleavage of caspase 3 and poly (ADP-ribose) polymerase 1 and increased
      deoxynucleotidyl transferase-mediated dUDP nick-end labeling staining, which is
      accompanied by increases in markers of vascular permeability. In contrast, MK2(-/
      ) mice are protected from pulmonary vascular permeability and apoptosis in
      response to LPS. Although there was no difference in activation of caspase 3 in
      MK2(-/-) compared with WT mice, interestingly, cleaved caspase 3 translocated to
      the nucleus in WT mice while it remained in the cytosol of MK2(-/-) mice in
      response to LPS. In separate experiments, LPS-induced apoptosis in human lung
      microvascular endothelial cells was also associated with nuclear translocation of
      cleaved caspase 3 and apoptosis, which were both prevented by MK2 silencing. In
      conclusion, our data suggest that MK2 plays a critical role in the development of
      apoptosis and pulmonary vascular permeability, and its effects on apoptosis are
      in part related to its ability to regulate nuclear translocation of cleaved
      caspase 3.

PMID- 24304497
TI  - Prevalence and belief in the continuation of female genital cutting among high
      school girls: a cross - sectional study in Hadiya zone, Southern Ethiopia.
AB  - BACKGROUND: Female Genital Cutting is a cultural practice among many ethnic
      groups in Ethiopia that has affected many girls over the past centuries. Although
      the trend is slowly decreasing in Ethiopia, the magnitude is still very high as
      the procedure has no known benefit but has many consequences. The objective of
      this study was to assess the prevalence and belief in the continuation of FGC
      among High School Girls in Hadiya Zone. METHODS: A cross-sectional quantitative
      survey was carried out among high school girls in Hadiya Zone from January to
      February 2011. A multi-staged cluster sampling method was used for sample
      selection. In total, 780 girls completed a self-administered questionnaire for
      this study. Statistical analysis was done using bivariate and multivariate
      logistic regression. RESULTS: Of 780 high school girls, 82.2% were circumcised at
      a mean age of 11(+/-2.3) years. Half of the total participants responded that FGC
      was being practiced in their village. About 60% of the circumcisions were
      performed by traditional circumcisers while health professionals had performed
      30% of them. A few of the circumcised girls (9.4%) supported their status as a
      circumcised girl, but only 5% believe in the continuation of FGC. The odds of
      being cut was higher among girls whose fathers and mothers had educational status
      under high school level (AOR = 2.04; 95% CI: 1.25, 3.09) and (AOR = 1.84; 95% CI:
      1.01, 3.38) respectively when compared to those whose parents had attended high
      school and above. The odds of believing in the continuation of FGC was 2.33(95%
      CI: 1.01, 5.33) times higher among those who responded that FGC was practiced in
      their areas. CONCLUSION: While there is an urgent need to stop the practice of
      FGC in Hadiya Zone, cultural beliefs related to the hygiene of female genitalia
      and other social factors contribute to sustaining the practice. Local
      organizations in collaboration with religious institutions and community leaders
      should work together to engage in a process of change within the entire community
      by arranging awareness creation programmes on the harmfulness of the practice
      especially in the rural areas of the zone.

PMID- 24304498
TI  - Accelerated bone growth in vitro by the conjugation of BMP2 peptide with
      hydroxyapatite on titanium alloy.
AB  - Titanium alloys have been widely used in orthopedic practice due to their
      inherent bioactivity, however it is still insufficient to truly and reliably
      incorporate into living bone. In this work, polydopamine film was employed to
      induce the growth of hydroxyapatite (HA) on titanium alloy to enhance its
      osteoconductivity. Bone morphogenetic protein-2 (BMP2) peptide was absorbed into
      the HA particles for osteoinductivity. The precipitation of HA and the existence
      of BMP2 peptide were examined by X-ray diffraction, X-ray photoelectron
      spectroscopy and fluorescence microscopy. The dissolution of HA and the release
      of BMP2 peptide were monitored by measuring the concentrations of calcium ions
      and BMP2 peptide in phosphate buffered saline solution, respectively. The effect
      of BMP2 peptide incorporated into HA coating on bone growth was evaluated in
      vitro by cell culture tests, including cell attachment, alkaline phosphatase
      (ALP) activity, and gene expression. The results show that the HA particles grown
      on the substrate are mediated by the polydopamine film. The BMP2 peptide is
      distributed uniformly on HA-coated substrate and released in a sustained manner.
      Moreover, the conjunction of HA and BMP2 peptide increases cell adhesion, ALP
      activity and gene expression of osteogenic markers, which are potentially useful
      in the development of enhanced orthopedic medical devices.

PMID- 24304499
TI  - Clinicopathological spectrum of ovarian sex cord-stromal tumors; 20 years'
      retrospective study in a developing country.
AB  - BACKGROUND: Ovarian sex cord stromal tumors are rare neoplasms as compared to
      epithelial tumors. No large study has been done in Pakistan to find out the
      frequencies of various sex cord stromal tumors and their clinicopathological
      behavior in our region. The purpose of our study was to determine the various
      histological patterns and clinical features of ovarian sex cord stromal tumors
      along with follow-up in our set-up. METHODS: It is a retrospective observational
      study. The study was conducted in section of Histopathology, Aga Khan University
      Hospital, Karachi, Pakistan. All reported cases of sex cord stromal tumors of
      ovary during 1992 to 2012 were retrieved. The retrieved slides were reviewed and
      patient demographics, clinical and pathological features were noted on proforma.
      SPSS Statistics Version 19 was used for all analyses. Data is expressed as
      absolute values and percentage or as mean +/- standard deviation (SD). RESULTS: A
      total of 480 cases of sex cord stromal tumors were retrieved. The median age was
      45 years. Bilaterality was observed in 4 cases. Of the different subtypes of sex
      cord stromal tumors, most common was adult granulosa cell tumor 211(43.9%). 24
      Juvenile granulosa cell tumors were retrieved (5%). Other types were fibromas 98
      (20.4%) fibrothecomas 47(9.8%), thecomas 26(5.4%), sertoli-leydig cell tumors
      34(7%), sclerosing stromal tumors 26 (5.4%), steroid cell tumors (10) and 4 cases
      of sex cord tumor with annular tubules. Of various immunohistochemical stains
      applied, Inhibin was frequently positive in all subtypes and focal cytokeratins
      were also seen commonly. Follow up information was available in 305 cases and out
      of these only 16 (5%) developed recurrence or metastasis. CONCLUSIONS: Sex cord
      stromal tumors are uncommon ovarian tumors in Pakistani population, with wide age
      range and diverse histological types having good prognosis. Immunohistochemical
      markers overlap with epithelial tumors so there is need to distinguish these two.

PMID- 24304500
TI  - Three types of dermal grafts in rats: the importance of mechanical property and
      structural design.
AB  - BACKGROUND: To determine how the mechanical property and micro structure affect
      tissue regeneration and angiogenesis, three types of scaffolds were studied.
      Acellular dermal matrices (ADM), produced from human skin by removing the
      epidermis and cells, has been widely used in wound healing because of its high
      mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co
      L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent
      poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this
      scaffold to enhance the CS mechanical property. These three different dermal
      substitutes-ADM, CS and PMCSs are different in the tensile properties and
      microstructure. METHODS: Several basic physical characteristics of dermal
      substitutes were investigated in vitro. To characterize the angiogenesis and
      tissue regeneration, the materials were embedded subcutaneously in Sprague-Dawley
      (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were
      harvested for histology, immunohistochemistry and real-time quantitative PCR (RT
      qPCR). RESULTS: In vitro studies demonstrated ADM had a higher Young's modulus
      (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state.
      Compared with ADMs and CSs, PMCSs with three-dimensional porous structures
      resembling skin and moderate mechanical properties can promote tissue ingrowth
      more quickly after implantation. In addition, the vascularization of the PMCS
      group is more obvious than that of the other two groups. The incorporation of a
      PLGA knitted mesh in CSs can improve the mechanical properties with little
      influence on the three-dimensional porous microstructure. After implantation,
      PMCSs can resist the contraction and promote cell infiltration, neotissue
      formation and blood vessel ingrowth, especially from the mesh side. Although ADM
      has high mechanical strength, its vascularization is poor because the pore size
      is too small. In conclusion, the mechanical properties of scaffolds are important
      for maintaining the three-dimensional microarchitecture of constructs used to
      induce tissue regeneration and vascularization. CONCLUSION: The results
      illustrated that tissue regeneration requires the proper pore size and an
      appropriate mechanical property like PMCS which could satisfy these conditions to
      sustain growth.

PMID- 24304501
TI  - A preliminary report on the feasibility of single-port thoracoscopic surgery for
      diaphragm plication in the treatment of diaphragm eventration.
AB  - INTRODUCTION: Thoracoscopic surgery is a popular widely used surgical technique
      in the treatment of common chest conditions. Conventional thoracoscopic surgery
      utilizes multiple small wounds for carrying out the procedure. Many procedures
      can also be performed with a single small port wound. In this study, we performed
      diaphragm plication using the techniques of single-port thoracoscopic surgery.
      MATERIALS AND METHODS: From July 1st, 2008 to December 31th, 2011, there were 21
      patients admitted to our hospital due to diaphragm eventration. All of them
      underwent diaphragm plication. The initial 11 patients underwent two-port
      thoracoscopic surgery while the subsequent 10 patients underwent single-port
      thoracoscopic surgery. RESULTS: The side of diaphragm eventration was on the left
      in all of the cases. The mean operative time was 87.3 minutes and the mean follow
      up time was 17 months. There was no procedure-related complication or mortality.
      The time required for surgery and the postoperative pain scores were similar in
      the two groups. CONCLUSION: Single-port thoracoscopic surgery for diaphragm
      plication is a safe procedure. It can serve as an alternative to conventional
      thoracoscopic approaches to diaphragm surgery.

PMID- 24304502
TI  - Salivary and serum level of CYFRA 21-1 in oral precancer and oral squamous cell
      carcinoma.
AB  - BACKGROUND: CYFRA 21-1, a constituent of the intermediate filament proteins of
      epithelial cells, is known to be increased in many cancers. This study was
      designed to estimate the levels of salivary and serum CYFRA 21-1 in patients with
      oral precancer and oral squamous cell carcinoma (OSCC) and compare them with
      healthy controls. MATERIALS AND METHODS: Each group comprised of 100 subjects.
      Saliva and blood samples were collected from patients with OSCC, premalignant
      subjects, and normal healthy subjects. Serum and salivary CYFRA 21-1 levels were
      measured by enzyme-linked immunosorbent assay. Appropriate statistical tests were
      employed to assess diagnostic potency of CYFRA 21-1. RESULTS: We found a
      significant increase in CYFRA 21-1 level in OSCC compared with PML and healthy
      subjects. Salivary CYFRA 21-1 levels in OSCC was threefold higher when compared
      to serum levels. PML group showed increased salivary CYFRA 21-1 when compared to
      control subjects, but it was significantly lower compared with OSCC. Receiver
      operator characteristic curve analysis showed salivary CYFRA 21-1 to have
      superior sensitivity in detecting OSCC compared with serum CYFRA 21-1.
      CONCLUSIONS: The outcome of this study suggests that salivary CYFRA 21-1 can be
      utilized as a biomarker in early detection of oral cancer.

PMID- 24304503
TI  - Father absence in the monogamous california mouse impairs social behavior and
      modifies dopamine and glutamate synapses in the medial prefrontal cortex.
AB  - The role of the father in psycho-affective development is indispensable. Yet, the
      neurobehavioral effects of paternal deprivation (PD) are poorly understood. Here,
      we examined the behavioral consequences of PD in the California mouse, a species
      displaying monogamous bonding and biparental care, and assessed its impact on
      dopamine (DA), serotonin (5-HT), and glutamate (GLU) transmission in the medial
      prefrontal cortex (mPFC). In adult males, deficits in social interaction were
      observed, when a father-deprived (PD) mouse was matched with a PD partner. In
      adult females, deficits were observed when matching a PD animal with a non-PD
      control, and when matching 2 PD animals. PD also increased aggression in females.
      Behavioral abnormalities in PD females were associated with a sensitized response
      to the locomotor-activating effect of amphetamine. Following immunocytochemical
      demonstration of DA, 5-HT, and GLU innervations in the mPFC, we employed in vivo
      electrophysiology and microiontophoresis, and found that PD attenuated the basal
      activity of low-spiking pyramidal neurons in females. PD decreased pyramidal
      responses to DA in females, while enhancing responses to NMDA in both sexes. We
      thus demonstrate that, during critical neurodevelopmental periods, PD leads to
      sex-dependent abnormalities in social and reward-related behaviors that are
      associated with disturbances in cortical DA and GLU neurotransmission. 

PMID- 24304504
TI  - Macronutrients, diet quality, and frailty in older men.
AB  - BACKGROUND: Frailty, a phenotype of multisystem impairment and expanding
      vulnerability, is associated with higher risk of adverse health outcomes not
      entirely explained by advancing age. We investigated associations of
      macronutrients, dietary fiber, and overall diet quality with frailty status in
      older community-dwelling men. METHODS: Participants were 5,925 men aged >= 65
      years enrolled in the Osteoporotic Fractures in Men (MrOS) study at six U.S.
      centers. Diet was assessed at baseline with a food frequency questionnaire. We
      assessed frailty status (robust, intermediate, or frail) at baseline and at a
      second clinic visit (a mean of 4.6 years later) using a slightly modified
      Cardiovascular Health Study frailty index. We used multinomial logistic
      regression to assess associations between macronutrient intake, dietary fiber,
      and the Diet Quality Index Revised with frailty status at baseline and at the
      second clinic visit. RESULTS: At baseline, 2,748 (46.4%) participants were
      robust, 2,681 (45.2%) were intermediate, and 496 (8.4%) were frail. Carbohydrate,
      fat, protein, and dietary fiber showed no consistent associations with frailty
      status. Overall diet quality exhibited fairly consistent associations with
      frailty status. The Diet Quality Index Revised was inversely associated with
      frail status relative to robust status at the baseline visit (odds ratio for Q5
      vs Q1 = 0.44, 95% confidence interval: 0.30, 0.63; p for trend < .0001) and at
      the second clinic visit (odds ratio for Q5 vs Q1 = 0.18, 95% confidence interval:
      0.03, 0.97; p for trend = .0180). CONCLUSIONS: Overall diet quality was inversely
      associated with prevalent and future frailty status in this cohort of older men.

PMID- 24304505
TI  - Control of vein patterning by intracellular auxin transport.
AB  - The vein networks of plant leaves are among the most spectacular expressions of
      biological pattern, and the principles controlling their formation have
      continually inspired artists and scientists. Control of vein patterning by the
      polar, cell-to-cell transport of the plant signaling molecule auxin--mediated in
      Arabidopsis primarily by the plasma-membrane-localized PIN1--has long been known.
      By contrast, the existence of intracellular auxin transport and its contribution
      to vein patterning are recent discoveries. The endoplasmic-reticulum-localized
      PIN5, PIN6, and PIN8 of Arabidopsis define an intracellular auxin-transport
      pathway whose functions in vein patterning overlap with those of PIN1-mediated
      intercellular auxin transport. The genetic interaction between the components of
      the intracellular auxin-transport pathway is far from having been resolved. The
      study of vein patterning provides experimental access to gain such a resolution-a
      resolution that in turn holds the promise to improve our understanding of one of
      the most fascinating examples of biological pattern formation.

PMID- 24304506
TI  - Structure and bonding of superconducting LaC2.
AB  - We have synthesized polycrystalline samples of superconducting LaC2 and
      investigated them by x-ray and neutron powder diffraction, magnetic
      susceptibility and heat capacity measurements. Depending on the preparation
      conditions we find superconductivity below ~1.8 K. A comparison of the
      superconducting anomaly in the heat capacity with theoretical predictions
      indicates LaC2 to be a weak-coupling BCS-type superconductor. Evidence for a
      structural phase transition has not been found from the neutron powder
      diffraction experiments carried out down to 4 K. A negative thermal expansion of
      the c lattice parameter was observed below ~50 K. The electronic structure of
      LaC2 has been calculated ab initio and it is compared with that of YC2. The
      carbon-carbon distance of LaC2 has been determined from the neutron powder
      diffraction experiments and it is compared and discussed with respect to those
      observed in other superconducting binary and ternary La and Y carbides and
      carbide halides.

PMID- 24304507
TI  - Participatory research to design a novel telehealth system to support the night
      time needs of people with dementia: NOCTURNAL.
AB  - Strategies to support people living with dementia are broad in scope, proposing
      both pharmacological and non-pharmacological interventions as part of the care
      pathway. Assistive technologies form part of this offering as both stand-alone
      devices to support particular tasks and the more complex offering of the "smart
      home" to underpin ambient assisted living. This paper presents a technology-based
      system, which expands on the smart home architecture, orientated to support
      people with daily living. The system, NOCTURNAL, was developed by working
      directly with people who had dementia, and their carers using qualitative
      research methods. The research focused primarily on the nighttime needs of people
      living with dementia in real home settings. Eight people with dementia had the
      final prototype system installed for a three month evaluation at home. Disturbed
      sleep patterns, night-time wandering were a focus of this research not only in
      terms of detection by commercially available technology but also exploring if
      automated music, light and visual personalized photographs would be soothing to
      participants during the hours of darkness. The NOCTURNAL platform and associated
      services was informed by strong user engagement of people with dementia and the
      service providers who care for them. NOCTURNAL emerged as a holistic service
      offering a personalised therapeutic aspect with interactive capabilities. 

PMID- 24304508
TI  - Objectively measured activity patterns among adults in residential aged care.
AB  - OBJECTIVES: To determine the feasibility of using the activPAL3(TM) activity
      monitor, and, to describe the activity patterns of residential aged care
      residents. DESIGN: Cross-sectional. SETTING: Randomly selected aged care
      facilities within 100 km of the Gold Coast, Queensland, Australia. PARTICIPANTS:
      Ambulatory, older (>=60 years) residential aged care adults without cognitive
      impairment. MEASUREMENTS: Feasibility was assessed by consent rate, sleep/wear
      diary completion, and through interviews with staff/participants. Activity
      patterns (sitting/lying, standing, and stepping) were measured via activPAL3(TM)
      monitors worn continuously for seven days. Times spent in each activity were
      described and then compared across days of the week and hours of the day using
      linear mixed models. RESULTS: Consent rate was 48% (n = 41). Activity patterns
      are described for the 31 participants (mean age 84.2 years) who provided at least
      one day of valid monitor data. In total, 14 (45%) completed the sleep/wear diary.
      Participants spent a median (interquartile range) of 12.4 (1.7) h sitting/lying
      (with 73% of this accumulated in unbroken bouts of >=30 min), 1.9 (1.3) h
      standing, and 21.4 (36.7) min stepping during their monitored waking hours per
      day. Activity did not vary significantly by day of the week (p >= 0.05); stepping
      showed significant hourly variation (p = 0.018). CONCLUSIONS: Older adults in
      residential aged care were consistently highly sedentary. Feasibility
      considerations for objective activity monitoring identified for this population
      include poor diary completion and lost monitors.

PMID- 24304509
TI  - Waitlist priority for hepatocellular carcinoma beyond milan criteria: a
      potentially appropriate decision without a structured approach.
AB  - Due to the risk of waitlist dropout from tumor progression, liver transplant
      candidates with hepatocellular carcinoma (HCC) within Milan criteria (MC) receive
      standardized exception points. An expansion of this process to candidates with
      HCC beyond MC has been proposed, though it remains controversial. This study
      sought to better define the utilization of exception points in candidates with
      HCC beyond MC and the associated outcomes. We reviewed all nonstandardized HCC
      applications that underwent formal regional review board evaluation between
      January 1, 2005 and March 2, 2011; 2184 initial HCC exception point applications
      were submitted. Of these, 41.9% fulfilled MC, 26.6% fulfilled University of
      California-San Francisco (UCSF) criteria and 17.6% exceeded UCSF criteria. The
      majority of applications were accepted: 89.8% within UCSF and 71.2% beyond UCSF.
      There was a significantly (p < 0.001) higher risk of death on the waitlist or
      within 90 days of waitlist removal for candidates within UCSF (12.4%) or beyond
      UCSF (13.0%) criteria, compared to candidates with HCC within MC (6.0%). However,
      posttransplant outcomes were similar. While these results suggest increasing
      access to candidates with HCC beyond MC, comprehensive documentation of tumor
      characteristics and of successful downstaging is needed to ensure priority is
      restricted to those with the highest likelihood of favorable posttransplant
      outcome.

PMID- 24304510
TI  - A qualitative study on the breastfeeding experiences of first-time mothers in
      Vientiane, Lao PDR.
AB  - BACKGROUND: The benefits of breastfeeding are well-recognised. The majority of
      first-time mothers in the Lao People's Democratic Republic however do not follow
      WHO guidelines of exclusively breastfeeding for the first six months, and less
      than half breastfeed for two years. UNICEF identified lack of exclusive
      breastfeeding as the second highest risk factor for under 5 mortality in Lao PDR,
      closely following lack of skilled delivery care. This study explored the reasons
      and influences behind first-time mothers' breastfeeding practices, as well as the
      role of attitudes, beliefs and experiences in influencing those practices.
      METHODS: A qualitative research design was chosen for this exploratory study. Two
      districts in Vientiane were selected, and in each district four focus group
      discussions, two with six first-time mothers and two with health staff were
      undertaken. In addition, sixteen in-depth interviews with first-time mothers and
      seven individual key informants were conducted. RESULTS: Participants
      demonstrated positive attitudes towards breastfeeding and recognised its
      importance. Despite this, breastfeeding practices were suboptimal. Few
      exclusively breastfed for the first six months of the baby's life and most of the
      first-time mothers included in the sample had stopped or planned to stop
      breastfeeding by the time the infant was 18 months of age. Work was named as one
      of the main reasons for less than ideal breastfeeding practices. Traditional
      beliefs and advice from health staff and the first-time mothers' own mothers,
      were important influences on breastfeeding practices. First-time mothers also
      cited experiencing tension when there were differences in advice they received
      from different people. CONCLUSION: Overall, the mothers were well-informed on the
      benefits of breastfeeding, and displayed positive attitudes towards it.
      Nevertheless, few maintained optimal breastfeeding practices in the first two
      years of the infant's life. Further effort needs to be directed at addressing
      knowledge and non-knowledge barriers to optimal breastfeeding practices. Of
      particular importance is working with employers, developing supportive employment
      policies, providing postnatal support and working with lay people and health
      professionals. Research is also needed to identify the optimal combination of
      interventions to promote good breastfeeding practices.

PMID- 24304512
TI  - Superoxide anions involved in sympathoexcitation and pressor effects of salusin
      beta in paraventricular nucleus in hypertensive rats.
AB  - AIMS: Salusin-beta in paraventricular nucleus (PVN) increases renal sympathetic
      nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR) and arginine
      vasopressin (AVP) release in hypertensive rats but not in normal rats. The
      present study was designed to investigate the downstream molecular mechanism of
      salusin-beta in the PVN in hypertension. METHOD: Renovascular hypertension was
      induced by two-kidney, one-clip (2K1C) in male SD rats. Acute experiments were
      carried out 4 weeks after 2K1C or sham operation under anaesthesia. RESULTS:
      MrgA1 mRNA expression and salusin-beta level in the PVN as well as plasma salusin
      beta level were increased in 2K1C rats. Bilateral PVN microinjection of salusin
      beta increased the RSNA, MAP and HR in 2K1C rats, which were abolished by the pre
      treatment with polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide
      anion scavenger tempol, the NAD(P)H oxidase inhibitor apocynin or the protein
      kinase C (PKC) inhibitor chelerythrine chloride (CLC), but not affected by the
      AT1 receptor antagonist losartan, the Mas receptor antagonist A-779, the NOS
      inhibitor L-NAME or the GABAA and GABAB receptor antagonists gabazine+CGP-35348.
      Salusin-beta-induced increases in superoxide anion level and NAD(P)H oxidase
      activity in the PVN were abolished by the PVN pre-treatment with CLC. Salusin
      beta increased AVP levels in rostral ventrolateral medulla and plasma, which were
      prevented by the pre-treatment with PEG-SOD, apocynin or CLC in 2K1C rats.
      Salusin-beta augmented the enhanced activity of PKC in the PVN in 2K1C rats.
      CONCLUSION: Protein kinase C-NAD(P)H oxidase-superoxide anions pathway in the PVN
      is involved in salusin-beta-induced sympathetic activation, pressor response and
      AVP release in renovascular hypertension.

PMID- 24304511
TI  - Allosteric induction of the CD4-bound conformation of HIV-1 Gp120.
AB  - BACKGROUND: HIV-1 infection of target cells is mediated via the binding of the
      viral envelope protein, gp120, to the cell surface receptor CD4. This interaction
      leads to conformational rearrangements in gp120 forming or revealing CD4 induced
      (CD4i) epitopes which are critical for the subsequent recognition of the co
      receptor required for viral entry. The CD4-bound state of gp120 has been
      considered a potential immunogen for HIV-1 vaccine development. Here we report on
      an alternative means to induce gp120 into the CD4i conformation. RESULTS:
      Combinatorial phage display peptide libraries were screened against HIV-1 gp120
      and short (14aa) peptides were selected that bind the viral envelope and
      allosterically induce the CD4i conformation. The lead peptide was subsequently
      systematically optimized for higher affinity as well as more efficient inductive
      activity. The peptide:gp120 complex was scrutinized with a panel of neutralizing
      anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide
      binding does not interfere with or obscure the CD4 binding site. CONCLUSIONS: Two
      surfaces of gp120 are considered targets for the development of cross
      neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By
      implementing novel peptides that allosterically induce the CD4i epitopes we have
      generated a viral envelope that presents both of these surfaces simultaneously.

PMID- 24304513
TI  - A biomarker based detection and characterization of carcinomas exploiting two
      fundamental biophysical mechanisms in mammalian cells.
AB  - BACKGROUND: Biomarkers allowing the characterization of malignancy and therapy
      response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are
      still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI
      like 1) has been used to identify the Apo10 protein epitope that marks tumor
      cells with abnormal apoptosis and proliferation. The transketolase-like protein 1
      (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even
      in the presence of oxygen (aerobic glycolysis/Warburg effect), which is
      concomitant with a more malignant phenotype due to invasive growth/metastasis and
      resistance to radical and apoptosis inducing therapies. METHODS: Expression of
      Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by
      immunohistochemistry. Both markers represent independent markers for poor
      survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope
      detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast
      cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74).
      RESULTS: Positive Apo10 and TKTL1 expression were associated with recurrence of
      the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an
      independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+
      subgroup showed the worst disease-free survival rate in OSCC.EDIM-Apo10 and EDIM
      TKTL1 blood tests allowed a sensitive and specific detection of patients with
      OSCC, breast cancer and prostate cancer before surgery and in after care. A
      combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity
      of 97.3% for the detection of carcinomas independent of the tumor entity.
      CONCLUSIONS: The combined detection of two independent fundamental biophysical
      processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific
      detection of neoplasia in a noninvasive and cost-effective way. Further
      prospective trials are warranted to validate this new concept for the diagnosis
      of neoplasia and tumor recurrence.

PMID- 24304514
TI  - Resveratrol prevents rapamycin-induced upregulation of autophagy and selectively
      induces apoptosis in TSC2-deficient cells.
AB  - The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling
      pathway is hyperactivated in a variety of cancers and disorders, including
      lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC), which are
      characterized by mutations in tumor suppressors TSC1 or TSC2. The concern with
      the use of mTORC1 inhibitors, such as rapamycin or its analogs (rapalogs), is
      that they cause upregulation of autophagy and suppress the negative feedback loop
      to Akt, which promotes cell survival, causing the therapy to be only partially
      effective, and relapse occurs upon cessation of treatment. In this study, we
      investigate the use of rapamycin in combination with resveratrol, a naturally
      occurring polyphenol, in TSC2-deficient cells. We tested whether such combination
      would prevent rapamycin-induced upregulation of autophagy and shift the cell fate
      toward apoptosis. We found that this combination treatment blocked rapamycin
      induced upregulation of autophagy and restored inhibition of Akt. Interestingly,
      the combination of rapamycin and resveratrol selectively promoted apoptosis of
      TSC2-deficient cells. Thus, the addition of resveratrol to rapamycin treatment
      may be a promising option for selective and targeted therapy for diseases with
      TSC loss and mTORC1 hyperactivation. 

PMID- 24304516
TI  - Observing live actin in the human trabecular meshwork.

PMID- 24304515
TI  - The association between stressful life events and depressive symptoms among
      Cypriot university students: a cross-sectional descriptive correlational study.
AB  - BACKGROUND: Previous findings suggest that stressful life events have a causal
      relationship with depressive symptoms. However, to date little is known
      concerning the contribution of the number and severity of recent stressful life
      events on the prevalence of depressive symptoms among university students. The
      aim of this study was to investigate the prevalence of depressive symptoms and
      its association with the number and the severity of self-reported stressful life
      events among university students in Cyprus. METHODS: A descriptive correlational
      design with cross sectional comparison was used. The CES-D scale was applied for
      the assessment of depressive symptoms and the LESS instrument for stressful life
      events. Both scales were completed anonymously and voluntarily by 1.500 students
      (response rate 85%). RESULTS: The prevalence of mild to moderate depressive
      symptoms [CES-D score between 16 and 21] and of clinically significant depressive
      symptoms [CES-D score >= 22] were 18.8% and 25.3% respectively. There were
      statistically significant differences in clinically significant depressive
      symptoms by gender, with higher rates among women (x(2) = 8.53, df = 1, p =
      0.003). Higher scores on the LESS scale were associated with more frequent
      reports of clinical depressive symptoms (x(2) = 70.63, df = 4, p < 0.001).
      Similarly, an association was found between the number of life events and
      clinical depressive symptoms (x(2) = 40.06, df = 4, p < 0.001). Logistic
      regression analysis after adjusting for socio-demographic characteristics
      confirmed that the responders who reported a high number (n = 12-21) of stressful
      life events during the previous year (OR = 2.64 95% CI: 1.02, 6.83) and a severe
      degree of stress due to these events (total LESS score > 351, OR = 3.03 95% CI:
      1.66, 5.39) were more likely to manifest clinical depressive symptoms.
      CONCLUSIONS: The high frequency of occurrence of depressive symptoms among
      Cypriot university students, as well as the strong association with stressful
      life events, highlights the need for psychological empowerment strategies towards
      students by institutional counseling services.

PMID- 24304517
TI  - Physiological differences explain the co-existence of different regeneration
      strategies in Mediterranean ecosystems.
AB  - * Fire and drought are selective driving forces in Mediterranean plants, and thus
      their ability to resprout or recruit after these disturbances is of paramount
      importance. The contrast in regeneration niche between resprouters and seeders,
      and each group's different root characteristics, suggest that they are subjected
      to different degrees of environmental stress and, consequently, to different
      evolutionary forces. * We compared leaf traits, xylem traits related to hydraulic
      efficiency and vulnerability to cavitation, and the physiological response to an
      imposed drought between seedlings of resprouters and seedlings of seeders. We
      used 12 species co-existing in Mediterranean basin ecosystems. * Major
      differences were found in the xylem architecture and leaf traits, and in the
      response to drought conditions. Seeders were more efficient at transporting water
      to leaves but formed, in turn, a safer xylem network. They also presented higher
      photosynthesis and transpiration rates, and earlier stomatal closure with
      drought, but good leaf dehydration tolerance. * Seeders and resprouters can be
      considered two syndromes whose different functional characteristics are related
      to water availability and drought responses. These characteristics, together with
      their differences in rooting habits, account for their distinct regeneration
      niches and, thus, their co-existence.

PMID- 24304518
TI  - Strategic ejaculation in simultaneously hermaphroditic land snails: more sperm
      into virgin mates.
AB  - BACKGROUND: It has been theorised that sperm competition promotes the strategic
      usage of costly sperm. Although sperm competition is thought to be an important
      driving force of reproductive traits in simultaneous hermaphrodites as well as in
      species with separate sexes, empirical studies on strategic ejaculation in
      simultaneous hermaphrodites are scarce. RESULTS: In the present study, we tested
      whether the simultaneously hermaphroditic land snail Euhadra quaesita adjusts the
      number of sperm donated according to the condition of the mate and whether the
      pattern of strategic ejaculation is in line with previously suggested theories.
      We found that individuals donated much more sperm when they copulated with a
      virgin mate than when they copulated with a non-virgin. CONCLUSION: The virgin
      biased pattern of ejaculation matches the theoretical prediction and suggests
      that sperm competition significantly influence the reproductive traits of
      simultaneously hermaphroditic land snails.

PMID- 24304519
TI  - The wish to be hated: Richard III's villainy in pursuit of the bad-enough object.
AB  - Richard III's legendary villainy, in addition to its obvious role in furthering
      his ambition for power, arguably had deeper psychological roots: motives embedded
      in the developmental unfolding of his complex relationship with a severely
      traumatized and rejecting mother. The theoretical formulations of Ronald
      Fairbairn are used to show that Richard's villainy preserved and perpetuated a
      specific object-tie to his mother, that of being her demonized and despised
      "child of hate," and that many of his victims, especially women, served as
      maternal surrogates in his lifelong quest to replicate his maternal "bad-enough
      object." Similar patterns of severe relational disturbance pervade many of the
      mother-son dyads portrayed in Shakespeare's other plays, a repetitive theme that
      may well be linked to the playwright's own mother's history of severe loss and
      depression during his infancy and its impact on her ability to provide her son
      with bountiful emotional nurturance. A collateral issue is also addressed-the
      narcissistically embedded bonding difficulties between parents and their disabled
      children, whose visible impairment is said to give rise to greater adjustment
      problems than does the medical severity of the condition itself. 

PMID- 24304520
TI  - Report cards and quality: do center report cards predict quality or simply
      predict the next report card?

PMID- 24304521
TI  - Prevalence, quantitative load and genetic diversity of Campylobacter spp. in
      dairy cattle herds in Lithuania.
AB  - BACKGROUND: Campylobacteriosis is a zoonotic disease, and animals such as
      poultry, pigs and cattle may act as reservoirs for Campylobacter spp. Cattle shed
      Campylobacter spp. into the environment and they can act as a reservoir for human
      infection directly via contact with cattle or their faeces or indirectly by
      consumption of contaminated food. The aim of this study was to determine the
      prevalence, the quantitative load and the genetic strain diversity of
      Campylobacter spp. in dairy cattle of different age groups. RESULTS: Faecal
      samples of 200 dairy cattle from three farms in the central part of Lithuania
      were collected and examined for Campylobacter. Cattle herds of all three farms
      were Campylobacter spp. positive, with a prevalence ranging from 75% (farm I),
      77.5% (farm II) to 83.3% (farm III). Overall, the highest prevalence was detected
      in calves (86.5%) and heifers (86.2%). In contrast, the lowest Campylobacter
      prevalence was detectable in dairy cows (60.6%). C. jejuni, C. coli, C. lari and
      C. fetus subsp. fetus were identified in faecal samples of dairy cattle. C.
      upsaliensis was not detectable in any sample. The high counts of Campylobacter
      spp. were observed in faecal material of dairy cattle (average 4.5 log10 cfu/g).
      The highest numbers of Campylobacter spp. were found in faecal samples from
      calves (average 5.3 log10 cfu/g), whereas, faecal samples from cows harboured the
      lowest number of Campylobacter spp. (average 3.7 log10 cfu/g). Genotyping by flaA
      PCR-RFLP analysis of selected C. jejuni isolates showed that some genotypes were
      present in all farms and all age groups. However, farm or age specific genotypes
      were also identified. CONCLUSIONS: Future studies are needed to investigate risk
      factors related to the degree of colonisation in cattle. Based on that, possible
      measures to reduce the colonisation and subsequent shedding of Campylobacter in
      cattle could be established. It is important to further investigate the
      epidemiology of Campylobacter in the cattle population in order to assess
      associated risks to public health.

PMID- 24304522
TI  - Prospective observational study on tracheal tube cuff pressures in emergency
      patients--is neglecting the problem the problem?
AB  - BACKGROUND: Inappropriately cuffed tracheal tubes can lead to inadequate
      ventilation or silent aspiration, or to serious tracheal damage. Cuff pressures
      are of particular importance during aeromedical transport as they increase due to
      decreased atmospheric pressure at flight level. We hypothesised, that cuff
      pressures are frequently too high in emergency and critically ill patients but
      are dependent on providers' professional background. METHODS: Tracheal cuff
      pressures in patients intubated before arrival of a helicopter-based rescue team
      were prospectively recorded during a 12-month period. Information about the
      method used for initial cuff pressure assessment, profession of provider and time
      since intubation was collected by interview during patient handover. Indications
      for helicopter missions were either Intensive Care Unit (ICU) transports or
      emergency transfers. ICU transports were between ICUs of two hospitals. Emergency
      transfers were either evacuation from the scene or transfer from an emergency
      department to a higher facility. RESULTS: This study included 101 patients
      scheduled for aeromedical transport. Median cuff pressure measured at handover
      was 45 (25.0/80.0) cmH2O; range, 8-120 cmH2O. There was no difference between
      patient characteristics and tracheal tube-size or whether anaesthesia personnel
      or non-anaesthesia personnel inflated the cuff (30 (24.8/70.0) cmH2O vs. 50
      (28.0/90.0) cmH2O); p = 0.113.With regard to mission type (63 patients underwent
      an emergency transfer, 38 patients an ICU transport), median cuff pressure was
      different: 58 (30.0/100.0) cmH2O in emergency transfers vs. 30 (20.0/45.8) cmH2O
      in inter-ICU transports; p < 0.001. For cuff pressure assessment by the
      intubating team, a manometer had been applied in 2 of 59 emergency transfers and
      in 20 of 34 inter-ICU transports (method was unknown for 4 cases each). If a
      manometer was used, median cuff pressure was 27 (20.0/30.0) cmH2O, if not 70
      (47.3/102.8) cmH2O; p < 0.001. CONCLUSIONS: Cuff pressures in the pre-hospital
      setting and in intensive care units are often too high. Interestingly, there is
      no significant difference between non-anaesthesia and anaesthesia personnel.
      Acceptable cuff pressures are best achieved when a cuff pressure manometer has
      been used. This method seems to be the only feasible one and is recommended for
      general use.

PMID- 24304523
TI  - Innovations in infection prevention: the infection prevention champions program.

PMID- 24304524
TI  - From heave to leave: understanding cyclic vomiting syndrome.
AB  - Cyclic vomiting syndrome (CVS) is an idiopathic functional gastrointestinal
      disorder that has been underrecognized in the adult population. Nausea, vomiting,
      and abdominal pain are common presentations to gastrointestinal nursing. There
      are multiple differential diagnoses the clinician must consider prior to a
      diagnosis of CVS to recognize the disorder. CVS occurs in 4 phases: (a)
      interepisodic, (b) prodromal, (c) vomiting, and (d) recovery. Each phase has
      specific treatment guidelines. There is no specific "cure" for CVS; proper
      management is key. Increasing awareness of CVS is paramount to its detection. CVS
      has been examined in the pediatric population and has often been considered a
      pediatric disorder. More recently, it has come to be recognized in the adult
      population. Proper care and management of these patients allow for better support
      for patients and their families who are often on the primary caregivers. Nurses
      are often on the front lines of care and knowledge of CVS from the beginning
      should lead to shortened hospital stays and optimal patient care. 

PMID- 24304526
TI  - Liver function tests in viremic and nonviremic chronic hepatitis B virus-infected
      pregnant women: importance of alanine aminotransferase/sodium ratio.
AB  - The major risk factor of perinatal transmission of Hepatitis B virus (HBV)
      infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the
      third trimester of pregnancy. The primary aim of this study was to evaluate the
      hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative
      chronic HBV-infected pregnant women and to correlate the findings with the
      presence or absence of viremia. Ninety-five consecutive chronic HBV-infected
      pregnant women were evaluated between the 28th and 32nd week of gestation. Viral
      load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were
      evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU.ml. In this
      study, viremic women exhibited significantly higher alanine aminotransferase
      (ALT), creatinine, and uric acid values as well as significantly lower white
      blood cell count compared with nonviremic women. There was also a significant
      statistical difference concerning ALT/sodium ratio between viremic and nonviremic
      women (0.20 +/- 0.22 vs. 0.10 +/- 0.09, respectively, p= .024). The optimal
      cutoff points discriminating those women with a high probability to have
      detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%,
      specificity = 61.5%, area under the receiver operating characteristic curve [AUC]
      = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC =
      72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio >= 0.11 had the
      higher probability of having serum HBV-DNA levels higher than 2000 IU/ml
      (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in
      maternal blood during the third trimester of pregnancy is significantly
      associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected
      pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher
      probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio
      greater than 0.11 could discriminate those women with HBV-DNA levels higher than
      2000 IU/ml. 

PMID- 24304527
TI  - The ileus and the oddities after colorectal surgery, continued.
AB  - In this second part of a series, complications related to colorectal surgery are
      highlighted and discussed, including anastomotic bleeding and hemorrhage, wound
      infection, anastomotic dehiscence and fistula formation, small bowel obstruction,
      and genitourinary complications. Prevention of complications may be improved by
      adequate selection of appropriate procedures for the patient, good surgical
      technique, and good postoperative care. 

PMID- 24304528
TI  - Exercise in individuals with inflammatory bowel disease.
AB  - There is increasing evidence that exercise may improve symptoms in individuals
      with inflammatory bowel disease (IBD). This study aims to explore issues that
      clinicians may need to consider when giving advice on exercise to such
      individuals. Limited existing evidence suggests that low to moderate physical
      activity may improve symptoms without any adverse effects in individuals with
      IBD. This is largely supported by the findings of the current case series of
      "exercising" individuals with IBD who reported that low- to moderate-intensity
      exercise (most commonly walking) had a positive effect on their mood, fatigue,
      weight maintenance, and osteoporosis. Overexertion was reported as a potential
      problem. Scant advice regarding exercise had been given by their healthcare
      professionals according to participants. The current literature and findings of
      this small case series suggest that exercise is likely to be beneficial and safe
      for individuals with IBD. However, more research is required on which
      recommendations for exercise could be based. 

PMID- 24304529
TI  - The importance of a person-centered approach in diagnostic workups of patients
      with irritable bowel syndrome: a qualitative study.
AB  - The aim of this study was to explore experiences of undergoing a diagnostic
      workup in patients with irritable bowel syndrome (IBS) at a unit for functional
      gastrointestinal disorders. Research has been sparse in addressing such
      experiences and the impact on well-being. Patients with IBS were invited to
      perform a workup of gastrointestinal tests. Of 120 patients who completed the
      tests, 20 were invited for an interview. Analysis of interviews was conducted
      through interpretative phenomenological analysis. One master theme emerged:
      validation of IBS experience inferred from three subthemes: the duality of
      suffering in IBS, coping with inflicted discomfort and pain, and capacity for
      resilience.Patients reported long-term suffering from symptoms including poor
      management within the healthcare organization. Despite inconvenience associated
      with the tests, patients expressed appreciation for professional attributes such
      as attentiveness that were perceived as a sense of being cared for and seen as a
      "person." During the workup, patients acquired greater knowledge of what IBS
      means, including knowledge about their own body functions and experienced relief
      that symptoms were not caused by any "dangerous" disease. Validation of IBS
      experience surfaced in the data implying that in such context, patients with IBS
      appear to find personal solutions to cope with everyday experiences and enhance
      autonomy. 

PMID- 24304530
TI  - Seeing the wood for the trees: 20 years of the Cochrane collaboration.

PMID- 24304531
TI  - Role delineation of the advanced practice registered nurse in gastroenterology.

PMID- 24304532
TI  - Role delineation of the licensed practical/vocational nurse in gastroenterology.

PMID- 24304533
TI  - Role delineation of the registered nurse in a staff position in gastroenterology.

PMID- 24304534
TI  - An alarming condition after upper gastrointestinal endoscopy: valsalva
      retinopathy.

PMID- 24304535
TI  - Surgical residents' perceptions of patient safety climate in Dutch teaching
      hospitals.
AB  - RATIONALE, AIMS AND OBJECTIVES: Explicit attention to patient safety during
      surgical training is needed to improve patient safety. A positive safety climate
      is associated with greater patient safety and is a requisite for safety teaching
      at the workplace. The Safety Climate Survey (SCS) measures perceptions of safety
      climate. This study aims to take a first step in validating the SCS for use among
      surgical residents in the Netherlands and to highlight opportunities for safety
      climate improvement through changes in surgical training in the Netherlands. It
      therefore assesses (1) if the SCS can be used to assess surgical residents'
      perceptions of the safety climate in Dutch teaching hospitals; and (2) how,
      according to SCS results, these residents perceive the safety climate in Dutch
      teaching hospitals. METHODS: In a cross-sectional study conducted in February
      2011, a Dutch translation of the SCS was administered to all general surgical
      residents in the Netherlands. Face validity and internal consistency were
      assessed, as were overall mean, means per item and significant differences in
      means between different groups of respondents. RESULTS: In total, 306 of 390
      (78%) residents completed the questionnaire. The SCS showed good face validity
      and internal consistency (Cronbach's alpha = 0.87). Residents reported an overall
      mean of 3.95 (standard deviation 0.51) out of a maximum score of 5.00, and 52%
      reported an overall mean of 4.00 or higher. Women and residents working in
      university hospitals gave significantly lower scores. Significant differences
      were also found among hospitals and among regions. Majority of the items scored
      less than 4.00. CONCLUSIONS: The SCS is potentially useful to measure surgical
      residents' perceptions of the patient safety climate in Dutch teaching hospitals.
      There is considerable room for improvement of the patient safety climate.
      Surgical training should include better feedback, formal patient safety teaching
      sessions at the workplace and specific attention to patient safety during the
      introduction in a new hospital, and supervisors should encourage surgical
      residents to report any patient safety concern they may have.

PMID- 24304536
TI  - Could glucose management after acute myocardial infarction cure myocardial
      damage?

PMID- 24304537
TI  - Differential effect of phosphodiesterase-3 inhibitors on sympathetic
      hyperinnervation in healed rat infarcts.
AB  - BACKGROUND: The effect of phosphodiesterase-3 (PDE-3) inhibitors on arrhythmia
      remains controversial, so the purpose of this study was to determine their
      differential effects on sympathetic hyperinnervation and the involved mechanisms
      in a rat model of myocardial infarction. METHODS AND RESULTS: After ligating the
      coronary artery, male Wistar rats were randomized to cilostazol or milrinone,
      chemically unrelated inhibitors of PDE-3, or vehicle for 4 weeks. The
      postinfarction period was associated with increased myocardial norepinephrine
      levels and oxidant release, as measured by myocardial superoxide level and
      dihydroethidine fluorescence staining. Infarcted rats in the milrinone- and
      cilostazol-treated groups had favorable ventricular remodeling with similar
      potency. Compared with milrinone, cilostazol significantly increased interstitial
      adenosine levels and reduced the production of myocardial cAMP and superoxide.
      Cilostazol significantly blunted sympathetic hyperinnervation, as assessed by
      immunofluorescent analysis of sympathetic innervation, and western blotting and
      real-time quantitative RT-PCR of nerve growth factor. Furthermore, the inhibitory
      effect of cilostazol on nerve growth factor was reversed by 8-cyclopentyl-1,3
      dipropylxanthine, a selective A1 receptor antagonist, and enhanced by tempol
      administration. In spite of similar arrhythmic vulnerability during programmed
      stimulation in both the vehicle-and cilostazol-treated groups, cilostazol did not
      have proarrhythmic effects compared with milrinone. CONCLUSIONS: Unlike
      milrinone, cilostazol has therapeutic neutrality in arrhythmias because of
      adenosine uptake inhibition, which antagonizes the PDE-3-induced increase of
      sympathetic reinnervation via mediation of an adenosine A1 receptor-mediated
      antioxidation. 

PMID- 24304538
TI  - Soluble ST2 and N-terminal pro-brain natriuretic peptide combination. Useful
      biomarker for predicting outcome of childhoodpulmonary arterial hypertension.
AB  - BACKGROUND: Some potential biomarkers have been reported recently in patients
      with pulmonary arterial hypertension (PAH), but the most clinically useful among
      these potential biomarkers, especially in childhood PAH, has not been identified.
      Therefore, this study investigated which biomarker is useful in assessing
      severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable
      PAH (HPAH). METHODS AND RESULTS: Fifty-nine patients who were younger than 16
      years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates
      were quantified: high-sensitivity troponin T, human heart fatty acid-binding
      protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3,
      soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin
      C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical
      outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated
      well with New York Heart Association class. On area under the receiver operating
      characteristic curve analysis, sST2 had a significantly good relationship with
      prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated
      sST2 and NT-proBNP level predicted poor outcome of the present patients with
      childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly
      worse prognosis among those with high NT-proBNP. CONCLUSIONS: The sST2 and NT
      proBNP combination is a useful biomarker to predict clinical condition and
      outcome in patients with childhood IPAH/HPAH.  

PMID- 24304539
TI  - Tracing a roadmap for vitamin B12 testing using the health technology assessment
      approach.
AB  - In our hospital, we are currently working to manage the appropriateness of
      vitamin B12 (B12) testing. Unfortunately, the classic evidence-based approach is
      unhelpful in this process and meta-analyzing data on the accuracy of this marker
      for cobalamin deficiency detection is misleading due to the lack of reference
      diagnostic methods. The approach currently proposed by the Health Technology
      Assessment (HTA) enables us to tackle the issue of B12 requests as a "healthcare"
      problem by considering the position of stakeholders involved in ordering,
      performing, interpreting the test, and receiving its results. Clinical
      expectations, methodological issues, and ethical aspects concerning the
      performance of the test can aid us in providing more guidance on the use of this
      marker. By building such structured information, hemodialysis patients and
      pregnant women have emerged as those groups preferentially requiring B12 testing,
      as it may potentially improve the clinical outcome. To avoid misinterpretation of
      B12 results more care should be taken in considering its biochemical and
      biological features, as well as the analytical issues. Spurious values obtained
      by current automated immunoassays may reflect suboptimal pre-analytical steps as
      well as known interfering conditions. Furthermore, the harmonization of results
      by available methods is still a far-reaching goal and the approach to interpret
      an individual's results should be improved. Tracing a roadmap for B12 testing by
      exploiting the HTA model to balance the stakeholders' claims and maximizing the
      patient's outcome may help to manage the marker demand.

PMID- 24304540
TI  - Antitumor mechanisms of amino Acid hydroxyurea derivatives in the metastatic
      colon cancer model.
AB  - The paper presents a detailed study of the biological effects of two amino acid
      hydroxyurea derivatives that showed selective antiproliferative effects in vitro
      on the growth of human tumor cell line SW620. Tested compounds induced cell cycle
      perturbations and apoptosis. Proteins were identified by proteomics analyses
      using two-dimensional gel electrophoresis coupled to mass spectrometry, which
      provided a complete insight into the most probable mechanism of action on the
      protein level. Molecular targets for tested compounds were analyzed by
      cheminformatics tools. Zinc-dependent histone deacetylases were identified as
      potential targets responsible for the observed antiproliferative effect. 

PMID- 24304541
TI  - Tackling structures of long noncoding RNAs.
AB  - RNAs are important catalytic machines and regulators at every level of gene
      expression. A new class of RNAs has emerged called long non-coding RNAs,
      providing new insights into evolution, development and disease. Long non-coding
      RNAs (lncRNAs) predominantly found in higher eukaryotes, have been implicated in
      the regulation of transcription factors, chromatin-remodeling, hormone receptors
      and many other processes. The structural versatility of RNA allows it to perform
      various functions, ranging from precise protein recognition to catalysis and
      metabolite sensing. While major housekeeping RNA molecules have long been the
      focus of structural studies, lncRNAs remain the least characterized class, both
      structurally and functionally. Here, we review common methodologies used to
      tackle RNA structure, emphasizing their potential application to lncRNAs. When
      considering the complexity of lncRNAs and lack of knowledge of their structure,
      chemical probing appears to be an indispensable tool, with few restrictions in
      terms of size, quantity and heterogeneity of the RNA molecule. Probing is not
      constrained to in vitro analysis and can be adapted to high-throughput sequencing
      platforms. Significant efforts have been applied to develop new in vivo chemical
      probing reagents, new library construction protocols for sequencing platforms and
      improved RNA prediction software based on the experimental evidence. 

PMID- 24304542
TI  - Prognostic discrimination using a 70-gene signature among patients with estrogen
      receptor-positive breast cancer and an intermediate 21-gene recurrence score.
AB  - The Oncotype DX(r) recurrence score (RS) predictor has been clinically utilized
      to appropriately select adjuvant chemotherapy for patients with estrogen receptor
      (ER)-positive early breast cancer. However, the selection of chemotherapy for
      patients with intermediate RSs remains controversial. We assessed the prognostic
      value of a 70-gene signature (70GS) among patients with ER-positive breast cancer
      and intermediate RSs. In addition, we sought to identify genes associated with
      poor 70GS scores based on gene expression profiling (GEP). GEP was performed
      using gene expression data from 186 patients with ER-positive breast cancer. The
      RS and 70GS score were calculated on the basis of GEP. Among 186 patients, 82 ER
      positive patients with intermediate RSs were identified. These patients were
      stratified by 70GS, overall survival (OS) significantly differed according to
      70GS (p=0.013). In a supervised hierarchical analysis according to 70GS, the
      expression of several representative genes for cell proliferation was
      significantly higher in the poor 70GS cluster than in the good 70GS cluster.
      Furthermore, among these patients, FOXM1, AURKA, AURKB, and BIRC5 displayed
      prognostic significance for OS. In conclusion, 70GS can help to discriminate
      survival differences among ER-positive patients with intermediate RSs. FOXM1,
      AURKA, AURKB, and BIRC5, are associated with poor 70GS scores.

PMID- 24304543
TI  - Smad3 deficiency ameliorates hepatic fibrogenesis through the expression of
      senescence marker protein-30, an antioxidant-related protein.
AB  - Smad3 is a key mediator of the transforming growth factor (TGF)-beta1 signaling
      pathway that plays central role in inflammation and fibrosis. In present study,
      we evaluated the effect of Smad3 deficiency in Smad3-/- mice with carbon
      tetrachloride (CCl4)-induced liver fibrosis. The animals were received CCl4 or
      olive oil three times a week for 4 weeks. Histopathological analyses were
      performed to evaluate the fibrosis development in the mice. Alteration of protein
      expression controlled by Smad3 was examined using a proteomic analysis. CCl4
      induced liver fibrosis was rarely detected in Smad3-/- mice compared to Smad3+/+.
      Proteomic analysis revealed that proteins related to antioxidant activities such
      as senescence marker protein-30 (SMP30), selenium-binding proteins (SP56) and
      glutathione S-transferases (GSTs) were up-regulated in Smad3-/- mice. Western
      blot analysis confirmed that SMP30 protein expression was increased in Smad3-/-
      mice. And SMP30 levels were decreased in CCl4-treated Smad3+/+ and Smad3-/- mice.
      These results indicate that Smad3 deficiency influences the proteins level
      related to antioxidant activities during early liver fibrosis. Thus, we suggest
      that Smad3 deteriorate hepatic injury by inhibitor of antioxidant proteins as
      well as mediator of TGF-beta1 signaling. 

PMID- 24304544
TI  - Effect of coronary artery bypass surgery on left ventricular function as assessed
      by strain and strain rate imaging.
AB  - INTRODUCTION: This study examined the effect of coronary artery revascularization
      on left ventricular function and the results of strain imaging for the detection
      of ischemia before and after coronary artery bypass graft (CABG) surgery.
      MATERIAL AND METHODS: Sixty-eight patients with a history of coronary artery
      disease (CAD) were included, prospectively. Conventional echocardiography and
      color tissue Doppler-derived strain-strain rate echocardiographic imaging were
      performed 24 hours before and 3 months after CABG surgery. RESULTS: While strain
      rate values of the basal septum, middle segment of the lateral wall, middle
      segment of the inferior wall, and middle and basal segments of the anterior wall
      were significantly increased, other segments did not change after the operation.
      The mean systolic strain rate value was significantly increased after the
      operation. Left ventricle strain values in the middle segment of the septum,
      middle and basal segments of the inferior wall, and middle and basal segments of
      the anterior wall were significantly increased after the operation. No
      significant difference was noted in the basal septum or the middle and basal
      segments of the lateral wall after the operation. The mean systolic strain value
      was significantly increased after the operation. CONCLUSION: The results of this
      study suggest that strain and strain rate echocardiography can provide an
      accurate evaluation of regional contractile function after CABG, even in the
      segments that are apparently normal.

PMID- 24304545
TI  - Magnetic phase transitions and superconductivity in strained FeTe.
AB  - The influence of hydrostatic pressure and ab-plane strain on the magnetic
      structure of FeTe is investigated from first principles. The results of
      calculations reveal a phase transition from antiferromagnetic double-stripe
      ordering at ambient pressure to ferromagnetic ordering at 2 GPa, or under
      compressive strain reducing the lattice parameter a by about 3%. In turn, a
      tensile strain of less than 2% induces the phase transition to antiferromagnetic
      single-stripe ordering. It corresponds to the superconducting FeTe thin films,
      thereby confirming that the superconducting state is positively linked to single
      stripe antiferromagnetic fluctuations. Both types of transition indicate that the
      position of Te atoms in the crystal is crucial for the magnetic and
      superconducting properties of iron chalcogenides.

PMID- 24304546
TI  - Bladder pain syndrome: validation of simple tests for diagnosis in women with
      chronic pelvic pain: BRaVADO study protocol.
AB  - BACKGROUND: Bladder pain syndrome (BPS), a condition with no gold standard
      diagnosis, comprises of a cluster of signs and symptoms. Bladder filling pain and
      bladder wall tenderness are two basic clinical features, present in a high number
      of sufferers. This study will validate the performance of these simple tests for
      BPS in women with chronic pelvic pain (CPP). METHODS/DESIGN: We will conduct a
      prospective test validation study amongst women with unexplained CPP presenting
      to gynaecology outpatient clinics. Two index tests will be performed: patient
      reported bladder filling pain and bladder wall tenderness on internal pelvic
      bimanual examination. A final diagnosis of BPS will be made by expert consensus
      panel. We will assess the rates of index tests in women with CPP; evaluate the
      correlation between index tests and Pelvic Pain Urgency/ Frequency (PUF)
      questionnaire results; and determine index test sensitivity and specificity using
      a range of analytical methods. Assuming a 50% prevalence of BPS and an 80% power
      approximately 152 subjects will be required exclude sensitivity of < 55% at 70%
      sensitivity. DISCUSSION: The results of this test validation study will be used
      to identify whether a certain combination of signs and symptoms can accurately
      diagnose BPS.

PMID- 24304547
TI  - Evaluation of exposure to contaminated drinking water and specific birth defects
      and childhood cancers at Marine Corps Base Camp Lejeune, North Carolina: a case
      control study.
AB  - BACKGROUND: Drinking water supplies at Marine Corps Base Camp Lejeune were
      contaminated with trichloroethylene, tetrachloroethylene, benzene, vinyl chloride
      and trans-1,2-dichloroethylene during 1968 through 1985. METHODS: We conducted a
      case control study to determine if children born during 1968-1985 to mothers with
      residential exposure to contaminated drinking water at Camp Lejeune during
      pregnancy were more likely to have childhood hematopoietic cancers, neural tube
      defects (NTDs), or oral clefts. For cancers, exposures during the first year of
      life were also evaluated. Cases and controls were identified through a survey of
      parents residing on base during pregnancy and confirmed by medical records.
      Controls were randomly sampled from surveyed participants who had a live birth
      without a major birth defect or childhood cancer. Groundwater contaminant fate
      and transport and distribution system models provided estimates of monthly levels
      of drinking water contaminants at mothers' residences. Magnitude of odds ratios
      (ORs) was used to assess associations. Confidence intervals (CIs) were used to
      indicate precision of ORs. We evaluated parental characteristics and pregnancy
      history to assess potential confounding. RESULTS: Confounding was negligible so
      unadjusted results were presented. For NTDs and average 1st trimester exposures,
      ORs for any benzene exposure and for trichloroethylene above 5 parts per billion
      were 4.1 (95% CI: 1.4-12.0) and 2.4 (95% CI: 0.6-9.6), respectively. For
      trichloroethylene, a monotonic exposure response relationship was observed. For
      childhood cancers and average 1st trimester exposures, ORs for any
      tetrachloroethylene exposure and any vinyl chloride exposure were 1.6 (95% CI:
      0.5-4.8), and 1.6 (95% CI: 0.5-4.7), respectively. The study found no evidence
      suggesting any other associations between outcomes and exposures. CONCLUSION:
      Although CIs were wide, ORs suggested associations between drinking water
      contaminants and NTDs. ORs suggested weaker associations with childhood
      hematopoietic cancers.

PMID- 24304548
TI  - Positive impact of Meniere's disorder on significant others as well as on
      patients: our experience from eighty-eight respondents.

PMID- 24304549
TI  - NCOA3 is a selective co-activator of estrogen receptor alpha-mediated
      transactivation of PLAC1 in MCF-7 breast cancer cells.
AB  - BACKGROUND: The placenta-specific 1 (PLAC1) gene encodes a membrane-associated
      protein which is selectively expressed in the placental syncytiotrophoblast and
      in murine fetal tissues during embryonic development. In contrast to its
      transcriptional repression in all other adult normal tissues, PLAC1 is frequently
      activated and highly expressed in a variety of human cancers, in particular
      breast cancer, where it associates with estrogen receptor alpha (ERalpha)
      positivity. In a previous study, we showed that ERalpha-signaling in breast
      cancer cells transactivates PLAC1 expression in a non-classical pathway. As the
      members of the p160/nuclear receptor co-activator (NCOA) family, NCOA1, NCOA2 and
      NCOA3 are known to be overexpressed in breast cancer and essentially involved in
      estrogen-mediated cancer cell proliferation we asked if these proteins are
      involved in the ERalpha-mediated transactivation of PLAC1 in breast cancer cells.
      METHODS: Applying quantitative real-time RT-PCR (qRT-PCR), Western Blot analysis
      and chromatin immunoprecipitation, we analyzed the involvement of NCOA1, NCOA2,
      NCOA3 in the ERalpha-mediated transactivation of PLAC1 in the breast cancer cell
      lines MCF-7 and SK-BR-3. RNAi-mediated silencing of NCOA3, qRT-PCR, Western blot
      analysis and ERalpha activation assays were used to examine the role of NCOA3 in
      the ERalpha-mediated regulation of PLAC1 in further detail. Transcript expression
      of NCOA3 and PLAC1 in 48 human breast cancer samples was examined by qRT-PCR and
      statistical analysis was performed using Student's t-test. RESULTS: We detected
      selective recruitment of NCOA3 but not NCOA1 or NCOA2 to the PLAC1 promoter only
      in ERalpha-positive MCF-7 cells but not in ERalpha-negative SK-BR-3 breast cancer
      cells. In addition, we demonstrate that silencing of NCOA3 results in a
      remarkable decrease of PLAC1 expression levels in MCF-7 cells which cannot be
      restored by treatment with estradiol (E2). Moreover, significant higher
      transcript levels of PLAC1 were found only in ERalpha-positive human breast
      cancer samples which also show a NCOA3 overexpression. CONCLUSIONS: In this
      study, we identified NCOA3 as a selective co-activator of ERalpha-mediated
      transactivation of PLAC1 in MCF-7 breast cancer cells. Our data introduce PLAC1
      as novel target gene of NCOA3 in breast cancer, supporting the important role of
      both factors in breast cancer biology.

PMID- 24304550
TI  - Intravitreal injections: a review of the evidence for best practice: comment.

PMID- 24304551
TI  - Effect of rosuvastatin therapy on troponin I release following percutaneous
      coronary intervention in nonemergency patients (from the TIP 3 study).
AB  - Several randomized studies have suggested that pretreatment with statins may
      reduce a periprocedural biomarker release in patients who underwent percutaneous
      coronary intervention (PCI); however, results remain controversial. The purpose
      of this study was to investigate the effect of a 1-day rosuvastatin therapy on
      troponin I release in patients who underwent nonemergency PCI. A total of 445
      patients with angina pectoris were randomly assigned to therapy with rosuvastatin
      (20 mg 12 hours before coronary angiography + 20 mg immediately before PCI;
      rosuvastatin group, 220 patients) or PCI without statin therapy (control group,
      225 patients). In patients taking statins (73%), rosuvastatin was added to their
      long-term statin therapy. The primary end point was the incidence of TnI
      microleak defined as TnI elevation >1.5* upper limit of normal, and the secondary
      end point was the incidence of post-PCI TnI elevation >3* upper limit of normal.
      The incidence of primary and secondary end point in the rosuvastatin versus
      control group was 13.6% versus 12% (p = 0.61) and 8.2% versus 7.1% (p = 0.67),
      respectively. Patients with C-reactive protein >=2.0 mg/L had a decreased release
      of post-PCI TnI in the rosuvastatin group (0.032 [0.010 to 0.143] MUg/L vs 0.056
      [0.018 to 0.241] MUg/L; p = 0.04). In conclusion, 1-day rosuvastatin therapy (20
      mg twice a day) did not influence post-PCI TnI release in patients with angina.
      However, these results suggest that, in patients with an advanced inflammatory
      status, rosuvastatin loading therapy might have a cardioprotective effect.

PMID- 24304552
TI  - Gender differences in exposure to SRH information and risky sexual debut among
      poor Myanmar youths.
AB  - BACKGROUND: Globally, the proportion of youths has been steadily increasing,
      especially in Asia. This vulnerable population has limited exposure to sexual and
      reproductive health (SRH) information leading to various reproductive health (RH)
      problems including risky sexual debut, unwanted pregnancy, unsafe abortion as
      well as STI/HIV infections. Among known social variations which influence youth's
      RH, gender differences are critical for planning necessary gender appropriate
      interventions. This study aimed to identify gender differences in exposure to SRH
      information and risky sexual debut as well as associated factors among Myanmar
      youths in poor suburban communities of Mandalay City. METHODS: A total of 444
      randomly selected youths (aged 15-24 years) from all poor, suburban communities
      in Mandalay City took part in our survey. Gender differences in exposure to SRH
      information and risky sexual debut were assessed by bivariate analysis.
      Multivariate logistic regression was used to confirm gender differences and
      identify independent factors associated with main outcomes separately for males
      and females as well as for both. RESULTS: Of 444 youths interviewed, 215 were
      males and 229 were females. Gender differences were seen in both exposures to SRH
      information (p = 0.013) and risky sexual debut (p = 0.003). These gender
      differences were confirmed by multivariate analysis even after adjusting for
      other risk factors. For exposure to SRH information, only age group and schooling
      status were significant factors for females. As well as those two factors, media
      exposure and parental guardianship were significant factors among males. Only
      positive norm of premarital sex increased the likelihood of risky sexual debut
      among males. In contrast, unwillingness at sexual debut was a risk factor and a
      higher education level was a protective factor for risky sexual debut among
      females. CONCLUSIONS: Limited exposure to SRH information and high risky sexual
      debut among poor youths were found. There were different influential factors for
      RH behaviors between males and females. Policy makers as well as local RH care
      providers should be aware of these differences. Dissemination of reliable SRH
      information among youths through possible mass media, especially among males, is
      an urgent issue.

PMID- 24304554
TI  - Expression of concern: Shivapurkar et al., "Differential Inactivation of Caspase
      8 in Lung Cancers", Cancer Biol Ther 2002; 1:65-9.

PMID- 24304553
TI  - Description of durum wheat linkage map and comparative sequence analysis of wheat
      mapped DArT markers with rice and Brachypodium genomes.
AB  - BACKGROUND: The importance of wheat to the world economy, together with
      progresses in high-throughput next-generation DNA sequencing, have accelerated
      initiatives of genetic research for wheat improvement. The availability of high
      density linkage maps is crucial to identify genotype-phenotype associations, but
      also for anchoring BAC contigs to genetic maps, a strategy followed for
      sequencing the wheat genome. RESULTS: Here we report a genetic linkage map in a
      durum wheat segregating population and the study of mapped DArT markers. The
      linkage map consists of 126 gSSR, 31 EST-SSR and 351 DArT markers distributed in
      24 linkage groups for a total length of 1,272 cM. Through bioinformatic
      approaches we have analysed 327 DArT clones to reveal their redundancy, syntenic
      and functional aspects. The DNA sequences of 174 DArT markers were assembled into
      a non-redundant set of 60 marker clusters. This explained the generation of
      clusters in very small chromosome regions across genomes. Of these DArT markers,
      61 showed highly significant (Expectation < E-10) BLAST similarity to gene
      sequences in public databases of model species such as Brachypodium and rice.
      Based on sequence alignments, the analysis revealed a mosaic gene conservation,
      with 54 and 72 genes present in rice and Brachypodium species, respectively.
      CONCLUSIONS: In the present manuscript we provide a detailed DArT markers
      characterization and the basis for future efforts in durum wheat map comparing.

PMID- 24304555
TI  - A randomized controlled trial for an individualized positive psychosocial
      intervention for the affective and behavioral symptoms of dementia in nursing
      home residents.
AB  - OBJECTIVES: This randomized controlled study tested the effectiveness of
      individualized activities, led by certified nursing assistants (CNAs), to
      increase positive and reduce negative affect and behavior among nursing home
      residents with dementia. METHOD: Nursing home residents with mild to advanced
      dementia (N = 180) were randomly assigned to usual care (UC, n = 93) or 1 of 2
      experimental conditions. Residents in the attention control group (AC, N = 43)
      participated in standardized one-to-one activities with their CNAs.
      Individualized Positive Psychosocial Intervention (IPPI) participants (n = 44)
      received a CNA-led activity matched to their interests and ability. Outcomes were
      residents' positive and negative affect and verbal and nonverbal behavior.
      RESULTS: The IPPI and AC groups experienced similar benefits-more pleasure,
      alertness, engagement, positive touch, and positive verbal behavior-compared with
      UC. The AC group displayed more anger, uncooperativeness, and very negative
      verbal behavior than UC or IPPI. DISCUSSION: This study demonstrates the value of
      individualized activities for nursing home residents with dementia. In a
      stringent test, residents were happier and less angry during a customized
      intervention compared with a standardized intervention. Even brief individualized
      CNA-led activities bring pleasure to nursing home residents and constitute an
      effective strategy to enhance positive affect and engagement in persons with
      dementia.

PMID- 24304556
TI  - Predictors of older adults' technology use and its relationship to depressive
      symptoms and well-being.
AB  - OBJECTIVE: To extend the empirical evidence regarding the predictors of older
      adults' use of information and communications technology (ICT) and to further
      examine its relationship to depressive symptoms and well-being. METHOD: This
      cross-sectional study utilized a sample of community-dwelling older adults from
      the National Health and Aging Trends Study (N = 6,443). Structural equation
      modeling was used to estimate the effects of predictor variables on ICT use and
      the effects of use on depressive symptoms and well-being. Tests of moderation by
      demographic characteristics and level of ICT use were also performed. RESULTS:
      Socioeconomic status (SES), age, and cognitive function accounted for
      approximately 60% of the variance in ICT use. SES was a stronger predictor for
      Blacks/African Americans, whereas cognitive function was a stronger predictor for
      Whites. ICT use was unrelated to depressive symptoms or well-being. However, it
      acted as a moderator, such that limitations in activities of daily living (ADLs)
      was a stronger predictor of depressive symptoms for high ICT users, whereas ill
      health was a stronger predictor for non/limited users. DISCUSSION: Findings do
      not support the claim that ICT use directly enhances mental health or well-being
      among older adults although it may protect against depressive symptoms for
      individuals coping with health conditions other than ADL impairments.

PMID- 24304557
TI  - Major quantitative trait loci control divergence in critical photoperiod for
      flowering between selfing and outcrossing species of monkeyflower (Mimulus).
AB  - * Divergence in flowering time is a key contributor to reproductive isolation
      between incipient species, as it enforces habitat specialization and causes
      assortative mating even in sympatry. Understanding the genetic basis of flowering
      time divergence illuminates the origins and maintenance of species barriers. * We
      investigated the genetics of divergence in critical photoperiod for flowering
      between yellow monkeyflowers Mimulus guttatus (outcrosser, summer flowering) and
      Mimulus nasutus (selfer, spring flowering). We used quantitative trait locus
      (QTL) mapping of F2 hybrids and fine-mapping in nearly isogenic lines to
      characterize the genomic regions underlying a > 2 h critical photoperiod
      difference between allopatric populations, and then tested whether the same QTLs
      control flowering time in sympatry. * We identified two major QTLs that almost
      completely explain M. nasutus's ability to flower in early spring; they are
      shared by allopatric and sympatric population pairs. The smaller QTL is
      coincident with one that differentiates ecotypes within M. guttatus, but the
      larger effect QTL appears unique to M. nasutus. * Unlike floral traits associated
      with mating system divergence, large interspecific differences in flowering
      phenology depend on only a few loci. Major critical photoperiod QTLs may be
      'speciation genes' and also restrict interspecific gene flow in secondary
      sympatry.

PMID- 24304558
TI  - Comparison of health-related quality of life between cancer survivors treated in
      designated cancer centers and the general public in Korea.
AB  - OBJECTIVE: We assessed health-related quality of life in cancer survivors treated
      in designated cancer centers when compared with the general population in Korea.
      METHODS: A multicenter survey was conducted from July through August 2008 using
      the quota-sampling approach. A general population sample was drawn from the
      Fourth Korean National Health and Nutrition Examination Survey, second year. We
      compared the multivariate-adjusted least square means of cancer patients with
      those of the general population to examine relationships between EuroQol five
      dimensional questionnaire components and cancer sites, cancer stage and time
      since diagnosis. The independent variables of responses to the EuroQol five
      dimensional questionnaire were evaluated using logistic regression analysis.
      RESULTS: Cancer patients scored significantly poorer on measures of self-care
      (means: stomach 1.25; lung 1.40; liver 1.27; colon 1.26; breast 1.27; cervical
      1.29 vs. general 1.18), engagement in usual activities (means: stomach 1.47; lung
      1.63; liver 1.45; colon 1.44; breast 1.46; cervical 1.47 vs. general 1.33) and
      anxiety/depression (means: stomach 1.41; lung 1.50; liver 1.41; colon 1.42;
      breast 1.50; cervical 1.47 vs. general 1.28). Those in the local stage scored
      significantly better on mobility (mean = 1.35) than the general population (mean
      = 1.40). Cancer patients, especially those with lung cancer, in the advanced
      stage and more than 5 years since diagnosis had poorer health-related quality of
      life than the general population. Some factors such as medical insurance and
      healthcare services were related to health-related quality of life among cancer
      patients. CONCLUSIONS: Health-related quality of life of cancer survivors with
      lung cancer at advanced stages, <1 year earlier and more than 5 years since
      diagnosis was poorer than that for the non-cancer control group, and these
      differences were statistically significant. Cancer survivors should be
      continuously observed and offered support.

PMID- 24304559
TI  - One-year follow-up of an educational intervention for palliative care
      consultation teams.
AB  - OBJECTIVE: This study explored how an educational intervention affects
      interdisciplinary palliative care consultation teams. METHODS: A pre-post
      questionnaire survey conducted before the intervention, as well as immediately,
      3, 6 and 12 months later. The outcome measurements were behavior (four domains-17
      items) and confidence (one domain-6 items). RESULTS: Of the 252 workshop
      participants (63 teams), 248 submitted a pre-intervention response, 240 responded
      immediately after, 198 after 3 months, 197 after 6 months and 184 after 12
      months. The behavior domain score significantly increased from pre- to 12 months
      post-intervention, as follows: 'regional partnership and consultation
      availability from medical personnel in region', from 15.0 to 17.8 (P < 0.001,
      effect size = 0.59); 'direct practice or care by member', from 12.8 to 13.4 (P <
      0.001, effect size = 0.26); 'provision of information to patient and family',
      from 11.4 to 12.5 (P < 0.001, effect size = 0.42). The confidence score for
      palliative care consultation teams activities significantly increased from 18.5
      pre-intervention to 20.2 at 12 months later (P < 0.001, effect size = 0.37). By
      the analysis according to the profession of the team member, the score changes
      for physicians and psychiatrists were larger than that for nurses and
      pharmacists. CONCLUSIONS: Participant behavior and confidence scores
      significantly increased after the educational intervention for the
      interdisciplinary team. In particular, physicians and psychiatrists showed the
      largest change. Future studies are needed to confirm the findings.

PMID- 24304560
TI  - Serum lactate and phosphate as biomarkers of intestinal ischemia in a Ugandan
      tertiary hospital: a cross-sectional study.
AB  - BACKGROUND: Intestinal ischemia is a common complication of intestinal
      obstruction and arises from impaired perfusion. The resultant local and systemic
      inflammatory response and bacterial translocation come with a significant degree
      of morbidity and mortality. This study therefore aimed to investigate the
      predictive value of elevated levels of serum lactate and phosphate as biomarkers
      of intestinal ischemia among patients with mechanical intestinal obstruction.
      METHODS: This was a cross-sectional analytical study done at Mulago Hospital in
      Uganda. Ethical approval was obtained. All eligible patients had a blood sample
      drawn for assay analysis. Determination of bowel ischemia status was by physical
      examination at laparotomy. Analyses were performed using Stata software, version
      10.1, and 2 * 2 tables were used to calculate sensitivity and specificity.
      RESULTS: Serum lactate was predictive of bowel ischemia, while phosphate was not.
      Of the 81 patients enrolled 70 qualified for analysis; 40/70 (57%) had ischemic
      bowel, while 30/70 (43%) had normal bowel. Among those with ischemic bowel, 28/40
      (70%) had reversible ischemia, and 12/40 (30%) had irreversible ischemia. Serum
      lactate assay had a sensitivity of 66% and specificity of 53% for bowel ischemia
      in general and a higher sensitivity of 71% and specificity of 80% for
      irreversible bowel ischemia.Lactate was predictive of bowel ischemia in general
      (p = 0.011), PPV = 14%, but more significantly predictive of irreversible
      ischemia (p = 0.009), PPV = 42%. NPV for lactate in both forms of ischemia was
      93%. Hernias (33/70, 47%) were the most common cause of intestinal obstruction.
      CONCLUSION: Serum lactate assay had moderate sensitivity for bowel ischemia due
      to acute mechanical intestinal obstruction. The assay can be used to aid
      diagnosis of bowel ischemia in low technology settings.

PMID- 24304561
TI  - Near equality in quality for medication utilization among older adults with
      diabetes with universal medication insurance in Ontario, Canada.
AB  - RATIONALE, AIMS AND OBJECTIVES: To determine whether demographic, community or
      health status disparities in cardioprotective medication utilization by diabetes
      patients exist under a universal drug insurance programme, and whether they
      narrow or widen during periods of increasing drug utilization. METHODS: We
      examined all prescriptions filled by all people with diabetes aged >=65 years in
      Ontario, Canada in annual cohorts from 1996 (n = 175 345) to 2010 (n = 504 093).
      We ascertained whether any disparities in use of three classes of
      cardioprotective medication (statins, all antihypertensives and renin-angiotensin
      aldosterone system inhibitors) existed, and whether disparities changed over
      time. RESULTS: Utilization of all three cardioprotective medication classes
      increased substantially over time, particularly statins (rate ratio per year:
      1.13, 95% confidence interval 1.11-1.15). We found no disparities associated with
      many of the demographic or community characteristics examined (including sex,
      income or rural residence). Use of statins was lower in those aged >=80 compared
      with younger age groups, although this disparity narrowed during the study.
      Persistently lower use of antihypertensives by minorities and by recent
      immigrants may be due to lower quality of care, barriers to access, or other
      patient or provider factors, which highlights the need for ongoing monitoring for
      disparities even in populations with universal drug insurance. Differences in
      medication utilization based on health status characteristics such as previous
      cardiovascular disease were medically indicated. CONCLUSIONS: Although a
      universal drug insurance programme was reasonably successful in ensuring few
      disparities in cardioprotective medication use by older patients with diabetes,
      disparities persisted for some subpopulations, so additional interventions
      continue to be needed to ensure equitable care.

PMID- 24304562
TI  - Left versus right lobe liver donation.

PMID- 24304564
TI  - Vortex ratchet reversal in an asymmetric washboard pinning potential subject to
      combined dc and ac stimuli.
AB  - The mixed-state resistive response of a superconductor thin film with an
      asymmetric washboard pinning potential subject to superimposed dc and ac currents
      of arbitrary amplitudes and frequency at finite temperature is theoretically
      investigated. The problem is considered in the single-vortex approximation,
      relying upon the exact solution of the Langevin equation in terms of a matrix
      continued fraction. The dc voltage response and the absorbed power in ac response
      are analyzed as functions of dc bias and ac current amplitude and frequency in a
      wide range of corresponding dimensionless parameters. Predictions are made of (i)
      a reversal of the rectified voltage at small dc biases and strong ac drives and
      (ii) a non-monotonic enhancement of the absorbed power in the nonlinear ac
      response at far sub-depinning frequencies. It is elucidated how and why both
      these effects appear due to the competition of the fixed internal and the
      tunable, dc bias-induced external asymmetry of the potential as the only reason.
      This is distinct from other scenarios used for explaining the vortex ratchet
      reversal effect so far.

PMID- 24304563
TI  - Upregulation of PGC-1alpha expression by Alzheimer's disease-associated pathway:
      presenilin 1/amyloid precursor protein (APP)/intracellular domain of APP.
AB  - Cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase
      generates amyloid-beta (Abeta) and APP intracellular domain (AICD) peptides.
      Presenilin (PS) 1 or 2 is the catalytic component of the gamma-secretase complex.
      Mitochondrial dysfunction is an established phenomenon in Alzheimer's disease
      (AD), but the causes and role of PS1, APP, and APP's cleavage products in this
      process are largely unknown. We studied the effect of these AD-associated
      molecules on mitochondrial features. Using cells deficient in PSs expression,
      expressing human wild-type PS1, or PS1 familial AD (FAD) mutants, we found that
      PS1 affects mitochondrial energy metabolism (ATP levels and oxygen consumption)
      and expression of mitochondrial proteins. These effects were associated with
      enhanced expression of the mitochondrial master transcriptional coactivator PGC
      1alpha and its target genes. Importantly, PS1-FAD mutations decreased PS1's
      ability to enhance PGC-1alpha mRNA levels. Analyzing the effect of APP and its
      gamma-secretase-derived cleavage products Abeta and AICD on PGC-1alpha expression
      showed that APP and AICD increase PGC-1alpha expression. Accordingly, PGC-1alpha
      mRNA levels in cells deficient in APP/APLP2 or expressing APP lacking its last 15
      amino acids were lower than in control cells, and treatment with AICD, but not
      with Abeta, enhanced PGC-1alpha mRNA levels in these and PSs-deficient cells. In
      addition, knockdown of the AICD-binding partner Fe65 reduced PGC-1alpha mRNA
      levels. Importantly, APP/AICD increases PGC-1alpha expression also in the mice
      brain. Our results therefore suggest that APP processing regulates mitochondrial
      function and that impairments in the newly discovered PS1/APP/AICD/PGC-1alpha
      pathway may lead to mitochondrial dysfunction and neurodegeneration. 

PMID- 24304566
TI  - SIRT7 an emerging sirtuin: deciphering newer roles.
AB  - Sirtuin7 (SIRT7) is a NAD(+)-dependent protein deacetylase which belongs to
      sirtuin family. Although sirtuin proteins have attracted a great deal of
      attention, little is known about SIRT7. SIRT7 participates in rDNA transcription
      in the nucleolus. However, recent reports show that SIRT7 has additional novel
      functions. This review summarizes all findings about SIRT7, and highlights its
      critical roles in cellular functions. 

PMID- 24304565
TI  - Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever
      vaccine in mice.
AB  - BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects
      livestock production and human health in sub-Saharan Africa, though epizootics
      have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated
      vaccine is available for livestock, there is currently no licensed human RVF
      vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal
      platform for development of a human RVF vaccine, given the low prevalence of
      neutralizing antibodies against them in the human population, and their excellent
      safety and immunogenicity profile in human clinical trials of vaccines against a
      wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the
      immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus
      vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which
      are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was
      assessed in comparison to a replication-deficient human adenovirus type 5 vector
      encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective
      immunity against RVF in mice. RESULTS: A single immunization with either of the
      vaccines conferred protection against RVF virus challenge eight weeks post
      immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust
      CD8+ T cell response. CONCLUSIONS: Together the results support further
      development of RVF vaccines based on replication-deficient adenovirus vectors,
      with ChAdOx1-GnGc being a potential candidate for use in future human clinical
      trials.

PMID- 24304567
TI  - Arecoline inhibits interleukin-2 secretion in Jurkat cells by decreasing the
      expression of alpha7-nicotinic acetylcholine receptors and prostaglandin E2.
AB  - The purpose of the present study was to explore the effect of arecoline on
      phytohemagglutinin (PHA)-stimulated interleukin-2 (IL-2) secretion, the
      expression of alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs),
      prostaglandin E2(PGE2) protein, and IL-2 mRNA in human lymphocyte cells (Jurkat
      cell line). The IL-2 and PGE2 were determined by enzyme-linked immunosorbent
      assay (ELISA). The expressions of phosphorylated extracellular signal-regulated
      kinase (ERK) and alpha7-nAChRs were determined by Western blotting. The level of
      IL-2 mRNA was determined by reverse-transcriptase polymerase chain reaction (RT
      PCR). Arecoline, in a dose-dependent manner, significantly decreased IL-2 and
      PGE2 secretion by Jurkat cells incubated with 0 or 5 MUg/ml 5 MUg/ml PHA. PGE2
      also significantly inhibited IL-2 secretion by Jurkat cells in a dose-dependent
      manner. In addition, reduced expression of PHA-induced ERK phosphorylation was
      observed in Jurkat cells treated with arecoline. PHA-enhanced IL-2 mRNA
      expression was also inhibited by arecoline. These results imply that arecoline
      inhibits the release of PGE2 and PHA-induced IL-2 secretion by Jurkat cells and
      that these effects seem to occur, at least in part, either through the
      attenuation of ERK in conjunction with a decrease of PHA-induced IL-2 mRNA
      expression. These results imply that arecoline inhibits the protein expression of
      alpha7-nAChRs , the release of PGE2 and PHA-induced IL-2 secretion by Jurkat
      cells. 

PMID- 24304568
TI  - Pterostilbene induces accumulation of autophagic vacuoles followed by cell death
      in HL60 human leukemia cells.
AB  - Pterostilbene, a naturally occurring structural analog of resveratrol, has been
      reported to exert antiproliferative and proapoptotic effects in various cancer
      types. Recently, it has been demonstrated to induce both autophagy and apoptosis
      in human bladder and breast cancer cell lines. The aim of this study was to
      evaluate the effects of pterostilbene on HL60 human leukemia cells. Cell
      morphology was examined using confocal and electron microscopy. Cell viability
      was determined by MTT, neutral red uptake and trypan blue exclusion assays. LC3
      processing was studied based on Western blotting and immunofluorescence analyses.
      Flow cytometry was used to study cell cycle distribution, phosphatidylserine
      externalization, caspase activation, disruption of mitochondrial membrane
      potential and intracellular production of reactive oxygen species. DNA
      degradation was examined by gel electrophoresis. We found that treatment of HL60
      cells with pterostilbene at the IC90 concentration resulted in the G0/G1 cell
      cycle arrest. Pterostilbene induced conversion of cytosolic LC3-I to membrane
      bound LC3-II and accumulation of large LC3-positive vacuolar structures.
      Pterostilbene also led to phosphatidylserine externalization, internucleosomal
      DNA fragmentation, caspase activation and disruption of mitochondrial membrane
      potential. Moreover, it did not induce oxidative stress. Our results suggest that
      pterostilbene induces accumulation of autophagic vacuoles followed by cell death
      in HL60 cells. 

PMID- 24304569
TI  - Induction of endoplasmic reticulum stress impairs insulin-stimulated vasomotor
      relaxation in rat aortic rings: role of endothelin-1.
AB  - Sustained endoplasmic reticulum (ER) stress and thus activation of the unfolded
      protein response is now thought to be the foundation of various chronic disorders
      including whole-body insulin resistance and cardiovascular disease. The purpose
      of the present study was to test the hypothesis that ER stress impairs insulin
      stimulated vasomotor reactivity. We report that experimental induction of ER
      stress in isolated aortic rings with tunicamycin (20 MUg/mL), a well-established
      inducer of ER stress, resulted in insulin-stimulated vascular contraction (-78+/
      21% at 1000 MUIU/mL; -100+/-27% at 10,000 MUIU/mL; all p<0.05) rather than
      relaxation (+23+/-7% at 1000 MUIU/mL; +43+/-8% at 10,000 MUIU/mL; all p<0.05).
      Importantly, we found that insulin-stimulated vascular contraction as a result of
      ER stress was largely eliminated in the presence of tezosentan (3 MUM), a
      nonselective endothelin-1 (ET-1) receptor blocker (+1+/-14% at 1000 MUIU/mL; +8+/
      17% at 10,000 MUIU/mL). Similarly, inhibition of ET-1 receptors fully restored
      the impairment of acetylcholine-mediated relaxation induced by ER stress (maximal
      relaxation: control = 94+/-2%, tunicamycin = 76+/-5%, tunicamycin + tezosentan =
      90+/-3). Furthermore, we demonstrate that ER stress caused a ~20-fold greater
      release of ET-1 from aortic endothelial cells under basal conditions as well as a
      ~15-fold increase under insulin-stimulated conditions (p<0.05). This ER stress
      mediated up-regulation in ET-1 release from endothelial cells was accompanied by
      a ~3-fold increase in phosphorylation of p44/22 MAPK (p<0.05), a known pathway by
      which insulin signaling activates ET-1. Together, these findings support the
      hypothesis that vascular ER stress-mediated activation of ET-1 may be an
      underlying cause of impaired vasomotor responsiveness to insulin and endothelial
      dysfunction. 

PMID- 24304570
TI  - Repeated restraint stress enhances glutamatergic transmission in the
      paraventricular nucleus of the rat hypothalamus.
AB  - Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine
      neurons of the hypothalamic paraventricular nucleus (PVN) play a key role in the
      activation of the hypothalamic-pituitary-adrenal axis (HPA). It is well known
      that excitatory and inhibitory inputs that regulate the activity of these neurons
      may undergo stress-related modifications; however, the effect of repeated
      restraint stress on the function of glutamatergic and GABAergic synapses on PVN
      parvocellular neuroendocrine neurons has not been fully understood so far.
      Adolescent male Wistar rats were subjected to restraint lasting 10 min and
      repeated twice daily for 3 days. Brain slices were prepared 24 hours after the
      last restraint session and were studied ex vivo. Whole-cell patch-clamping was
      used to record spontaneous excitatory and inhibitory postsynaptic currents
      (sEPSCs and sIPSCs) from parvocellular neuroendocrine neurons of the PVN.
      Repeated restraint stress resulted in an increase in the mean frequency of sEPSCs
      and in a decrease in the rise time and the decay time constant of sEPSCs. There
      was no change in the mean amplitude of sEPSCs. The parameters characterizing
      sIPSCs also remained unaltered. In addition, the injected current vs. spiking
      rate ratio of parvocellular neurons was decreased. In conclusion, restraint
      stress, repeated for 3 days, selectively enhances excitatory synaptic inputs to
      parvocellular neurons of the PVN, these modifications being accompanied with a
      decrease in the intrinsic excitability of PVN neuroendocrine parvocellular
      neurons. 

PMID- 24304571
TI  - Early-effect of bariatric surgery (Scopinaro method) on intestinal hormones and
      adipokines in insulin resistant Wistar rat.
AB  - Bariatric surgery consists in duodenal exclusion from the food passage in obese
      patients with coexistent type 2 diabetes. Nowadays bariatric surgery is
      considered the most effective method of glycemic index normalization and insulin
      resistance reduction. Recent results on obese and non-obese rats showed remission
      of type 2 diabetes symptoms within few days after the surgery. The aim of the
      present work was to analyze the mechanisms of neuro-hormonal regulation
      responsible for early normalization of metabolic syndrome after bariatric
      surgery. In present study the concentration of selected intestinal hormones and
      adipokines in blood plasma and gastrointestinal tissues were analyzed. Study was
      conducted on Wistar rats. Animals were divided into three groups (each n=6):
      control (SH) shame-operated rats; animals in which visceral fat tissue was
      extracted (LP); and rats in which Scopinaro bariatric surgery was performed
      (BPD). Immunochemistry analysis of blood plasma showed decrease of insulin
      concentration in BPD and LP and increase of polypeptide YY (PYY) in BPD group as
      compared to the control. In duodenal mucosa homogenates the tendency to reduce
      insulin in LP and BPD group, and increase PYY and visfatin in BPD group was
      observed. Histometry analysis showed reduction of mucosa thickness in excluded
      segments of gastrointestinal tract in BPD group as compared to the SH and LP.
      Concluding, model studies on rats allowed better understanding of mechanisms
      important for early normalization of glycemic index and insulin resistance
      reduction in rats. 

PMID- 24304572
TI  - Placental leptin and its receptor genes expression in pregnancies complicated by
      type 1 diabetes.
AB  - Type 1 diabetes mellitus (T1DM) is still associated with increased risk for
      severe maternal and fetal complications but their pathomechanism remains unclear.
      We investigated into possible role of placental leptin (LEP) and its receptor
      gene (LEPR) in T1DM pregnancies. Fourty nine pregnant women with T1DM and
      singleton pregnancy were enrolled into the study. Control group consisted of 15
      healthy pregnant women in uncomplicated, singleton gestation. We observed higher
      expression of LEP and LEPR in T1DM placentas in comparison to healthy subjects.
      We also noticed greater expression of LEP and LEPR in T1DM pregnancies with large
      for gestational age (LGA) and appropriate for gestational age (AGA) fetuses in
      comparison to small for gestational age (SGA) diabetic fetuses and controls. We
      found a significant positive correlation between placental LEP and LEPR
      expression and neonatal birthweight in overweight T1DM subjects. No such a
      correlation was found in T1DM subjects with normal weight and controls. We
      conclude that increased placental LEP and LEPR expression may have a role in
      stimulating fetal overgrowth in T1DM pregnancy. 

PMID- 24304573
TI  - Comparison of anti-inflammatory properties of peroxisome proliferator-activated
      receptor gamma agonists rosiglitazone and troglitazone in prophylactic treatment
      of experimental colitis.
AB  - Non-specific inflammatory bowel disease (IBD), including ulcerative colitis and
      Crohn's disease, is a chronic noninfectious inflammatory disease whose incidence
      is increasingly high, especially in the developed countries. Effective methods of
      its treatment and prevention of recurrences are still under investigation.
      Amongst the options to control effectively the inflammatory processes of the
      gastrointestinal tract are thiazolidinediones - peroxisome proliferator-activated
      receptors gamma (PPAR-gamma) agonists, whose beneficial effects on macroscopic
      and histopathological features of colitis have been confirmed in numerous
      studies. In the present study, possible effects of PPAR-gamma agonists
      rosiglitazone and troglitazone enhancing the resistance of colonic tissues to the
      damaging factor were examined and compared. Rats received the food with 0.01%
      rosiglitazone or troglitazone for 4 weeks; during the final 2 weeks, colitis
      inducing 1.5% DSS (dextran sodium sulfate) was additionally administered in the
      drinking water. The large intestine specimens were microscopically evaluated and
      the levels of Th1- (IL-2, INF) and Th2-dependent (IL-4, IL-10) cytokines were
      determined in the serum and intestinal homogenates. Prophylactic treatment with
      rosiglitazone and troglitazone ameliorated colitis substantially down-regulating
      the microscopic inflammatory parameters. Rosiglitazone and troglitazone
      administered before the induction of colitis exerted comparable effects on
      colitis. Both substances significantly reduced the levels of pro-inflammatory
      cytokines and increased the levels of inflammation-limiting cytokines. We
      conclude that thiazolidinedione drugs are likely to be successfully used for
      therapy and prevention of non-specific bowel diseases. 

PMID- 24304574
TI  - Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon
      anastomosis and counteracts cuprizone brain injuries and motor disability.
AB  - Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel
      disease and multiple sclerosis, and thereby, shown to equally counteract the
      models of both of those diseases. For colitis, cysteamine (400 mg/kg
      intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7,
      and 14) were used. BPC 157 (10 MUg/kg, 10 ng/kg) was applied either
      intraperitoneally once time daily (first application immediately after surgery,
      last at 24 hours before sacrifice) or per-orally in drinking water (0.16
      MUg/ml/12 ml/day till the sacrifice) while controls simultaneously received an
      equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12
      ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with
      standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg
      intragastrically/day) was combined with BPC 157 (in drinking water 0.16 MUg or
      0.16 ng/ml/12 ml/day/rat + 10 MUg or 10 ng/kg intragastrically/day) till the
      sacrifice at day 4. In general, the controls could not heal cysteamine colitis
      and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the
      same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and
      accelerated damaging process; nerve damage appeared in various brain areas, with
      most prominent damage in corpus callosum, laterodorsal thalamus, nucleus
      reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently
      less nerve damage in all damaged areas, especially in those areas that otherwise
      were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and
      impaired forelimb function. Thereby, this experimental evidence advocates BPC 157
      in both inflammatory bowel disease and multiple sclerosis therapy. 

PMID- 24304575
TI  - Effect of sitagliptin on the working memory and reference memory in type 2
      diabetic Sprague-Dawley rats: possible role of adiponectin receptors 1.
AB  - Type 2 diabetes mellitus (DM) is associated with increased incidence of
      behavioral changes and memory loss. Memory loss could be caused by Alzheimer's
      disease (AD) and vascular dementia (VaD). So, we aimed to investigate the effect
      of sitagliptin in improving the working and reference memories in diabetic rats.
      Thirty six male Sprague-Dawley rats divided equally (n=12) into three groups:
      control, type 2 DM and type 2 DM treated with DPP-4 inhibitor (sitagliptin) for
      one month (10 mg/kg) orally. Working memory and reference memory were assessed by
      using the holeboard memory test. In all rats, serum glucose, insulin,
      adiponectin, total cholesterol (TC), TG, low (LDL) and high (HDL) density
      lipoprotein with calculation of the homeostasis model of assessment-insulin
      resistance index (HOMA-IR) and atherogenic index. The hypothalamus was separated
      for determination of the acetylcholine level and adiponectin receptors 1 (Adipo
      R1) m-RNA expression. Type 2 diabetic rats exhibited a significant decrease in
      both working and reference memories, with increased glucose, insulin and HOMA-IR.
      The adiponectin level, acetylcholine content of the hypothalamus and Adipo R1 m
      RNA expression were significantly reduced. Treatment with sitagliptin
      significantly improved the working and reference memories with significant
      reduction in the glucose, insulin and HOMA-IR. Moreover, sitagliptin increased
      significantly the acetylcholine content of the hypothalamus and Adipo R1
      expression. In conclusion, sitagliptin might improve the cognitive function of
      the diabetic rats and the hypothalamic acetylcholine level possibly through
      increased AdipoR1 expression. 

PMID- 24304576
TI  - Experimental healing of preexisting gastric ulcers induced by hormones
      controlling food intake ghrelin, orexin-A and nesfatin-1 is impaired under
      diabetic conditions. A key to understanding the diabetic gastropathy?
AB  - Hormonal peptides like ghrelin, orexin A (OXA) or nesfatin-1 not only regulate
      appetite, which is their basic biological function, but also contribute to
      mechanisms responsible for maintaining integrity of the gastric mucosa. Previous
      studies including those from our laboratory have revealed that their
      gastroprotective effect results from cooperation with other factors responsible
      for protection of the gastric mucosa, including prostaglandin (PG) synthesis
      pathway, nitric oxide (NO) and the sensory afferent fibres releasing the
      vasoactive neurotransmitters. The aim of the present study was to determine
      whether ghrelin, orexin-A (OX-A) or nesfatin-1 with their protective effect on
      the gastric mucosa, also can modify the healing of chronic gastric ulcers.
      Furthermore, an attempt was made to explain participation of these peptides in
      healing processes of chronic gastric ulcers with comorbid conditions for the
      human beings resulted from diabetes mellitus. In our study, a model of gastric
      ulcers caused by concentrated acetic acid to induce the chronic gastric ulcers
      was used, while the clinical condition corresponding to diabetes was induced by
      single injection of streptozotocin (STZ). We found that ghrelin, OX-A and
      nesfatin-1 accelerate dynamics of the acetic acid ulcers healing, confirmed by a
      reduction in the ulcer area and this effect was accompanied by an increase in
      gastric blood flow at the ulcer margin. Destruction of sensory afferent fibres
      with capsaicin or blocking of vanilloid receptors with capsazepine resulted in a
      significant reduction of ghrelin, OX-A and nesfatin-1-induced acceleration of
      ulcer healing. Similar results were obtained when an NO-synthase blocker, L-NNA
      was used in a combination with these peptides. Moreover, it was found that OX-A
      and nesfatin-1 failed to accelerate the healing process under diabetic condition
      because both these hormones induced reduction in the ulcer area and the increase
      in blood flow in normal, non-diabetic rats were completely lost in the group of
      animals with diabetes. Treatment with OX-A and nesfatin-1 increased superoxide
      dismutase (SOD) mRNA expression even in acetic acid ulcers concurrent with
      diabetes. However, the treatment with OX-A and nesfatin-1 failed to alter the
      increase in gastric mucosal mRNA expression for ghrelin and hypoxia-inducible
      factor 1-alpha (HIF-1alpha), this latter effect that had been strongly pronounced
      in diabetic animals. We conclude that the hormonal peptides involved in the
      regulation of satiety and hunger such as ghrelin, OX-A and nesfatin-1 contribute
      to the process of chronic gastric ulcers healing cooperating with NO and sensory
      afferent nerve endings releasing vasoactive neuropeptide CGRP. Furthermore, OX-A
      and nesfatin-1, the two relatively unrecognized peptides, play an essential role
      in healing process of chronic gastric ulcers activating the gastric blood flow at
      ulcer margin and the mucosal regeneration and both ulcer healing and accompanying
      hyperemia at ulcer margin are greatly impaired during diabetes. Possibly, loss of
      the healing effect of these peptides during diabetes results from an interaction
      with radical generation processes as reflected by an increase of mRNA expression
      for SOD as well as the failure of their attenuating activity on proinflammatory
      factors such as HIF-1alpha. 

PMID- 24304577
TI  - Diverging oxidative damage and heat shock protein 72 responses to endurance
      training and chronic testosterone propionate treatment in three striated muscle
      types of adolescent male rats.
AB  - The aim of the study was to assess the effects of a combination of anabolic
      androgenic steroid abuse and endurance training during adolescence on selected
      aspects of oxidative stress and antioxidant defenses in various striated muscle
      types. The effects were studied of testosterone propionate (TP) treatment (8 and
      80 mg/kg/week, for 6 weeks), given alone or in combination with moderate
      intensity endurance training, starting at adolescence, on thiobarbituric acid
      reactive substances and heat shock protein 72 (Hsp72) contents, and androgen
      receptorm(AR) mRNA level in the heart left ventricle, soleus and extensor
      digitorum longus of male Wistar rats. TP treatment alone markedly elevated
      thiobarbituric acid-reactive substances only in the left ventricle and soleus;
      this effect was but marginally enhanced by endurance training. The training alone
      markedly elevated Hsp72 content in all muscles studied. TP treatment alone dose
      dependently upregulated Hsp72, while the lower TP dose slightly curtailed the
      effect of the training. Low-dose TP treatment alone elevated, whereas high-dose
      TP treatment alone lowered androgen receptor mRNA level in the soleus and
      extensor digitorum longus. Endurance training alone elevated AR mRNA in all
      muscles studied, whereas TP treatment dose-dependently counteracted this effect.
      Exercise-associated rise in body temperature was significantly less in the TP
      treated rats. We came to the conclusion that chronic suprapharmacological TP
      treatment might exert a protective effect on muscle cell proteins in adolescent
      sedentary rats, but it markedly enhanced lipid peroxidation. These effects were
      unlikely to result from an androgen receptor-mediated genomic action of
      testosterone. Exercise-related heat stress, and not oxidative stress, was mainly
      responsible for Hsp72 upregulation in striated muscles of chronic TP-treated
      endurance-trained adolescent male rats. 

PMID- 24304578
TI  - Spleen volume changes during adrenergic stimulation with low doses of
      epinephrine.
AB  - It is generally accepted that the spleen contraction is a consequence of humoral
      stimulation but recent data suggest a role of neural mechanisms. This study
      tested the hypothesis that the reduction in spleen size in response to low dose
      epinephrine infusion is a consequence of neurally mediated unloading of
      baroreceptors. Continuous ultrasonic measurements of spleen volume in response to
      intravenous infusion of low doses of epinephrine (0.06 MUg/kg/min for 6 minutes,
      followed 0.12 MUg/kg/min for 3 minutes) were performed with simultaneous
      continuous noninvasive measurements of cardiovascular parameters in thirteen
      subjects. In subgroup of six subjects we also continuously measured muscle
      sympathetic nerve activity (MSNA) as an index of peripheral sympathetic
      activation. Significant spleen contraction (~30%, p=0.008) was observed early
      after the onset of epinephrine infusion and was preceded by a decrease in total
      peripheral resistance (41%, p=0.001) and mean arterial pressure (6.2%, p=0.02)
      and an increase in heart rate (27%, p=0.001) and total MSNA (120%, p=0.02). Our
      results demonstrate rapid spleen contraction induced by low-dose epinephrine
      infusion in conditions of decreased blood pressure and increased MSNA suggesting
      that the spleen may represent a constitutive part of the sympathetic nervous
      system under stressful situations. 

PMID- 24304579
TI  - Ghrelin accelerates the healing of oral ulcers in non-sialoadenectomized and
      sialoadenectomized rats.
AB  - Ghrelin exhibits protective and therapeutic effect in different parts of the
      gastrointestinal tract. The aim of the present study was to examine the influence
      of ghrelin administration on the healing of oral ulcers in rats with intact
      salivary gland and in sialoadenectomized rats. Gingival and lingual ulcers were
      induced by acetic acid. After induction of ulcers, rats were treated with saline
      or ghrelin for six days. In rats with intact salivary glands and induction of
      oral ulcers, administration of ghrelin significantly increased the healing rate
      of these ulcers. This result was associated with a significant increase in
      mucosal blood flow and cell proliferation, and a decrease in concentration of pro
      inflammatory interleukin-1beta in gingival and lingual mucosa. Sialoadenectomy
      decreased cell proliferation and increased concentration of pro-inflammatory
      interleukin-1beta in oral mucosa, as well as reduced the healing rate of gingival
      and lingual ulcers. Administration of ghrelin reversed deleterious effect of
      sialoadenectomy and increased the healing rate of oral ulcers above a value
      observed in rats with intact salivary glands. CONCLUSIONS: Treatment with ghrelin
      accelerates healing of oral ulcers in salivary glands-intact rat, as well as in
      rats with reduced salivary secretion evoked by sialoadenectomy. Mechanisms of
      beneficial effects of ghrelin administration involve an increase in mucosal blood
      flow and cell proliferation, as well as a reduction in local inflammation.

PMID- 24304580
TI  - Clinical evaluation and cellular electrophysiology of a recessive CLCN1 patient.
AB  - Here we present the case of a 32-year-old female patient with myotonia congenita.
      She carried two mutations in the CLCN1 gene that encodes the chloride channel ClC
      1: p.Phe167Leu, which was previously identified in several families, and
      p.Val536Leu, which has been previously reported but not yet characterized by
      electrophysiological investigations. The patient's symptoms included generalized
      stiffness, myotonia, and muscle cramps mostly localized in the lower limbs. These
      symptoms started during childhood and worsened over the following years. The
      symptoms were exacerbated by low outside temperature, rest, stress, and fasting
      and were improved by mild exercise, suggesting a warm-up phenomenon. The mutation
      p.Phe167Leu has previously been associated with a slight shift in the overall
      open probability. Here we further analysed this mutation to extrapolate the
      voltage-dependence of the fast and slow gates. In our experimental conditions,
      p.Phe167Leu exclusively affected the slow gate, increasing the minimum open
      probability and displacing the voltage-dependence toward depolarized potentials.
      p.Val536Leu showed more severe effects, dramatically influencing the slow gate as
      well as modifying properties of the fast gate. Co-expression of the mutants in a
      human cell line to reproduce the compound heterozygous condition of the patient
      produced channels with altered voltage-dependence of the slow gate but a restored
      fast gate. The alteration of the slow mechanism was reflected by the relative
      open probability, reducing the contribution of ClC-1 channels in maintaining the
      resting membrane potential of skeletal muscles and thus explaining the myotonic
      phenotype of the patient. 

PMID- 24304581
TI  - Combination of SLC administration and Tregs depletion is an attractive strategy
      for targeting hepatocellular carcinoma.
AB  - BACKGROUND: Secondary lymphoid tissue chemokine (SLC) is a key CC chemokine for
      chemotaxis of immune cells and has been an attractive candidate for anti-tumor
      treatments. However, among the immune cells recruited by SLC to tumors, the CD25+
      Foxp3+ regulatory T cells (Tregs) compromise the anti-tumor effects. In this
      study, we proposed the combination therapy of intratumoral co-administration of
      SLC and anti-CD25 monoclonal antibodies (mAbs). We hypothesized that the
      intratumoral injections of SLC and depletion of Tregs would have stronger
      inhibition effects on the progression of hepatocellular carcinoma (HCC) in mice.
      METHODS: C57BL/6 mice were inoculated subcutaneously with the murine HCC cell
      line, and mice with visible tumors were treated intratumorally with SLC, SLC plus
      anti-CD25 mAbs or the control antibodies. The percentages of Tregs, effector CD8+
      T cells and CD4+ T cells were checked in the tumors, lymph nodes, spleen and
      liver at regular intervals. The levels of intratumoral IL-12, IFN-gamma, IL-10
      and TGF-beta1 were evaluated. The final anti-tumor effects were measured by the
      tumor volume and weight as well as the intratumoral activity of MMP2 and MMP9.
      Bone-marrow-derived dendritic cells were used to explore the mechanisms of
      maturation induced by SLC in vitro. RESULTS: Our experiments showed the
      combination therapy significantly decreased the frequency of Tregs, and increased
      CD8+ T cells and CD4+ T cells at tumor sites. These alterations were accompanied
      by an increased level of IL-12 and IFN-gamma, and decreased level of IL-10 and
      TGF-beta1. Unexpectedly, we observed a significantly decreased percentage of
      Tregs, and increased CD8+ T cells and CD4+ T cells in the lymph nodes, spleen and
      liver after the combination therapy. The growth and invasiveness of HCC was also
      maximally inhibited in the combination therapy compared with the SLC alone.
      Furthermore, we confirmed SLC induced the maturation of DCs via NF-kappaB p65 and
      this maturation would benefit the combination therapy. CONCLUSIONS: Our data
      demonstrated that intratumoral co-administration of SLC and anti-CD25 mAbs was an
      effective treatment for HCC, which was correlated with the altered tumor
      microenvironment and systemically optimized percentages of Tregs, CD8+ T cells
      and CD4+ T cells in peripheral immune organs.

PMID- 24304583
TI  - Gray- and white-matter anatomy of absolute pitch possessors.
AB  - Absolute pitch (AP), the ability to identify a musical pitch without a reference,
      has been examined behaviorally in numerous studies for more than a century, yet
      only a few studies have examined the neuroanatomical correlates of AP. Here, we
      used MRI and diffusion tensor imaging to investigate structural differences in
      brains of musicians with and without AP, by means of whole-brain vertex-wise
      cortical thickness (CT) analysis and tract-based spatial statistics (TBSS)
      analysis. APs displayed increased CT in a number of areas including the bilateral
      superior temporal gyrus (STG), the left inferior frontal gyrus, and the right
      supramarginal gyrus. Furthermore, we found higher fractional anisotropy in APs
      within the path of the inferior fronto-occipital fasciculus, the uncinate
      fasciculus, and the inferior longitudinal fasciculus. The findings in gray matter
      support previous studies indicating an increased left lateralized posterior STG
      in APs, yet they differ from previous findings of thinner cortex for a number of
      areas in APs. Finally, we found a relation between the white-matter results and
      the CT in the right parahippocampal gyrus. In this study, we present novel
      findings in AP research that may have implications for the understanding of the
      neuroanatomical underpinnings of AP ability. 

PMID- 24304582
TI  - Characteristics and determinants of T-cell phenotype normalization in HIV-1
      infected individuals receiving long-term antiretroviral therapy.
AB  - OBJECTIVES: Although combination antiretroviral therapy (cART) can restore CD4 T
      cell numbers in HIV infection, alterations in T-cell regulation and homeostasis
      persist. We assessed the incidence and predictors of reversing these alterations
      with cART. METHODS: ART-naive adults (n = 4459) followed within the Canadian
      Observational Cohort and exhibiting an abnormal T-cell phenotype (TCP) prior to
      cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T
      cell count (< 532 cells/MUL), (2) lost T-cell homeostasis (CD3 < 65% or > 85%) or
      (3) CD4:CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP,
      CD4 and CD8 T-cell percentages and absolute counts were also analysed for a
      median duration of 3.14 years [interquartile range (IQR) 1.48-5.47 years].
      Predictors of TCP normalization were assessed using adjusted Cox proportional
      hazards models. RESULTS: At baseline, 96% of pateints had CD4 depletion, 32% had
      lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third
      of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had
      normalized their TCP. In a multivariable model adjusted for age, measurement
      frequency and baseline regimen, higher baseline CD4 T-cell counts and time
      dependent viral suppression independently predicted TCP normalization [hazard
      ratio (HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/MUL
      increase; P <= 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58
      8.61); P-value <= 0.01]. CONCLUSIONS: Despite effective cART, complete TCP
      recovery occurred in very few individuals and was associated with baseline CD4 T
      cell count and viral load suppression. HIV-induced alterations of the TCP are
      incompletely reversed by long-term ART.

PMID- 24304584
TI  - Modulation of hippocampus-prefrontal cortex synaptic transmission and disruption
      of executive cognitive functions by MK-801.
AB  - Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine
      and MK-801 are known to impair cognitive function in rodents and humans, and
      serve as a useful tool to study the cellular basis for pathogenesis of
      schizophrenia cognitive symptoms. In the present study, we tested in rats the
      effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC)
      synaptic transmission and the performance in 2 cognitive tasks. We found that
      single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases
      of the HPC-mPFC response, which shares the common expression mechanisms with long
      term potentiation (LTP). But unlike LTP, its induction required no enhanced or
      synchronized synaptic inputs, suggesting aberrant characteristics. In parallel,
      rats injected with MK-801 showed impairments of mPFC-dependent cognitive
      flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of
      MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel
      within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic
      glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation,
      ameliorated the MK-801-induced impairment of spatial working memory. Our results
      show a novel form of use-independent long-lasting potentiation in HPC-mPFC
      pathway induced by MK-801, which is associated with impairment of HPC-mPFC
      projection-dependent cognitive function. 

PMID- 24304585
TI  - C-4 gem-dimethylated oleanes of Gymnema sylvestre and their pharmacological
      activities.
AB  - Gymnema sylvestre R. Br., one of the most important medicinal plants of the
      Asclepiadaceae family, is a herb distributed throughout the World, predominantly
      in tropical countries. The plant, widely used for the treatment of diabetes and
      as a diuretic in Indian proprietary medicines, possesses beneficial digestive,
      anti-inflammatory, hypoglycemic and anti-helmentic effects. Furthermore, it is
      believed to be useful in the treatment of dyspepsia, constipation, jaundice,
      hemorrhoids, cardiopathy, asthma, bronchitis and leucoderma. A literature survey
      revealed that some other notable pharmacological activities of the plant such as
      anti-obesity, hypolipidemic, antimicrobial, free radical scavenging and anti
      inflammatory properties have been proven too. This paper aims to summarize the
      chemical and pharmacological reports on a large group of C-4 gem-dimethylated
      pentacyclic triterpenoids from Gymnema sylvestre. 

PMID- 24304586
TI  - Phenolic esters of O-desmethylvenlafaxine with improved oral bioavailability and
      brain uptake.
AB  - O-Desmethylvenlafaxine (desvenlafaxine, ODV) is a recently approved
      antidepressant which in some clinical studies failed to meet a satisfactory end
      point. The aim of this study was to prepare a series of phenolic esters of ODV
      and evaluate their potential as ODV prodrugs with improved brain uptake. Fifteen
      phenolic esters (compounds 1a-o) were synthesized and their pharmacokinetic
      profiles evaluated in rat. The four compounds producing the highest relative
      bioavailability of ODV in rat (compounds 1c, 1e, 1n, 1o) were then studied to
      evaluate their brain uptake. Of these four compounds, compound 1n (the
      piperonylic acid ester of ODV) demonstrated the highest C(max) of ODV both in the
      rat hypothalamus and total brain. Finally the pharmacokinetics of 1n were
      evaluated in beagle dog where the increase in relative bioavailability of ODV was
      found to be as great as in rat. This high relative bioavailability of ODV coupled
      with its good brain penetration make 1n the most promising candidate for
      development as an ODV prodrug.

PMID- 24304587
TI  - Sodium valproate induces cell senescence in human hepatocarcinoma cells.
AB  - Hepatocarcinogenesis is associated with epigenetic changes, including histone
      deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially
      valuable approach for hepatocellular carcinoma treatment. In present study, we
      evaluated the anticancer effects of sodium valproate (SVP), a known HDAC
      inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the
      proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP
      treatment caused a large and flat morphology change, positive SA-beta-gal
      staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low
      dose SVP treatment also increased acetylation of histone H3 and H4 on p21
      promoter, accompanied by up-regulation of p21 and down-regulation of RB
      phosphorylation. These observations suggested that a low dose of SVP could induce
      cell senescence in hepatocarcinoma cells, which might correlate with
      hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB
      phosphorylation. Since the effective concentration inducing cell senescence in
      hepatocarcinoma cells is clinically available, whether a clinical dose of SVP
      could induce cell senescence in clinical hepatocarcinoma is worthy of further
      study. 

PMID- 24304588
TI  - Chemical composition and biological activity of essential oils of Origanum
      vulgare L. subsp. vulgare L. under different growth conditions.
AB  - This research was aimed at investigating the essential oil production, chemical
      composition and biological activity of a crop of pink flowered oregano (Origanum
      vulgare L. subsp. vulgare L.) under different spatial distribution of the plants
      (single and binate rows). This plant factor was shown to affect its growth, soil
      covering, fresh biomass, essential oil amount and composition. In particular, the
      essential oil percentage was higher for the binate row treatment at the full
      bloom. The chemical composition of the oils obtained by hydrodistillation was
      fully characterized by GC and GC-MS. The oil from plants grown in single rows was
      rich in sabinene, while plants grown in double rows were richer in ocimenes. The
      essential oils showed antimicrobial action, mainly against Gram-positive
      pathogens and particularly Bacillus cereus and B. subtilis. 

PMID- 24304589
TI  - The prevalence and determinants of impaired fasting glucose in the population of
      Taiwan.
AB  - BACKGROUND: A current prevalence and relevant risk factors for impaired fasting
      glucose (IFG) have been reported by various ethnic groups and countries. By
      contrast, nationwide data for the incidence of IFG in Taiwan have not been
      presented in the past 15 years. The aim for this manuscript was to estimate the
      prevalence of IFG and associated risk factors in the population of Taiwan.
      METHODS: For this cross-sectional research, we used a nationally representative
      sample (N = 2604) obtained from the 2005-2008 Nutrition and Health Survey in
      Taiwan (NAHSIT), and adopted a stratified multistage sampling design. The tools
      employed for data collection included questionnaire interviews, anthropometry
      measurements, and laboratory analysis. RESULTS: The prevalence of IFG among
      adults in Taiwan is 35.8% (a fasting glucose level between 100 and 125 mg/dl is
      considered abnormal). An estimated number of people with IFG is 6.5 million. A
      higher prevalence of IFG is observed in men younger than 65 years compared to
      women. However, this trend is reversed for the elderly population. The factors
      significantly associated with IFG include the following: sex, age, overweight (27
      > BMI >= 24), obesity (BMI >= 27), waist circumference (men >= 90 cm, women >= 80
      cm), hypertension, and hyperlipidemia. CONCLUSIONS: IFG among adults in Taiwan is
      a health concern that requires attention. We recommend targeting the younger
      population, especially overweight and obese men between the ages of 19 and 40
      years, to provide applicable healthy lifestyle counseling and services.
      Furthermore, appropriate screening of elderly people is required to detect
      undiagnosed IFG cases and provide early intervention and treatment.

PMID- 24304590
TI  - Regulatory forum commentary: is unexpected immunostimulation manageable in
      pharmaceutical development?
AB  - One of the biggest challenges in drug development is interpretation of findings
      suggestive of immunostimulation, particularly when the findings are unexpected
      based on the known mechanism of action of the drug. Findings suggestive of
      immunostimulation do not necessarily preclude development of the drug. By
      understanding mechanism, the patient population, and species differences and by
      careful clinical monitoring, many of the drugs that produce immunostimulation can
      be successfully developed. This opinion piece describes various types of
      immunostimulation and a risk assessment strategy for management of unexpected
      immunostimulation in toxicity studies. 

PMID- 24304591
TI  - Phenethyl isothiocyanate induces calcium mobilization and mitochondrial cell
      death pathway in cholangiocarcinoma KKU-M214 cells.
AB  - BACKGROUND: Phenethyl isothiocyanate (PEITC) is a cancer chemopreventive agent
      from cruciferous vegetables. Cholangiocarcinoma (CCA) is a chemo-resistant cancer
      with very poor prognosis. We evaluated the effects of PEITC on induction of
      apoptotic cell death in relation to cellular glutathione (GSH) and mitochondrial
      function of a CCA cell line, KKU-M214. METHODS: Cytotoxic effects of PEITC on a
      CCA cell line, KKU-M214, and a reference cell line, Chang cells were evaluated.
      To delineate mechanisms of cell death, the following parameters were measured;
      GSH and superoxide levels as the oxidative status parameters, apoptosis related
      proteins levels using Western blotting. Cellular free calcium level and
      mitochondrial transmembrane potential were also measured. RESULTS: PEITC induced
      apoptotic cell death of both KKU-M214 and Chang cells. After PEITC treatment,
      both cells showed decrease of Bcl-xl and increase of Bax levels. While KKU-M214
      cells released AIF, Chang cells released cytochrome c, with subsequent activation
      of caspase 3 and 9, upon PEITC treatment. PEITC induced superoxide formation in
      both cells, although it seemed not play a role in cell death. PEITC caused GSH
      redox stress in different ways in two cell types, because N-acetylcysteine (NAC)
      prevented redox stress in Chang but not in KKU-M214 cells. The loss of
      mitochondrial transmembrane potential was induced by PEITC concurrent with GSH
      stress, but was not a primary cause of cell death. The rapid increase of free
      calcium level in cytosol was associated with cell death in both cell lines. These
      events were prevented by NAC in Chang cells, but not in KKU-M214 cells.
      CONCLUSION: PEITC induced cell death KKU-M214 cells and Chang cells via increase
      of cellular calcium mobilization and activation of mitochondrial cell death
      pathway. The effects of PEITC on the redox stress was mediated via different ways
      in CCA and Chang cells because NAC could prevent redox stress in Chang cells, but
      not in KKU-M214 cells. The multiple effects of PEITC may be useful for the
      development of novel chemotherapy for CCA.

PMID- 24304592
TI  - Synthesis and biological evaluation of Combretastatin A-4 derivatives containing
      a 3'-O-substituted carbonic ether moiety as potential antitumor agents.
AB  - BACKGROUND: Combretastatin A-4 (CA-4), which is an excellent antineoplastic
      agent, was isolated from Combretum caffrum. To date, structural modification
      studies of CA-4 have focused predominantly on the construction of new therapeutic
      agents for drug discovery. As a part of our ongoing work towards the modification
      of natural products, we have focused on the 3'-O-substituent groups in the B-ring
      of CA-4 under the hypothesis that these novel derivatives will possess good
      bioactivities and behave as effective antiproliferative pro-drugs. RESULTS: A
      series of novel CA-4 derivatives, which contained a 3'-O-substituted carbonic
      ether moiety, were synthesized and evaluated for their antitumor activities
      against four tumor cell lines, including MDA-MB-231, MCF-7, K562 and A549 cells.
      These derivatives exhibited clear antitumor activities, and CA-4E, in particular,
      showed the highest bioactivity of all of the derivatives tested against all four
      tumor cell lines, with IC50 values in the range of 1 to 180 nM. Based on its high
      bioactivity, CA-4E was subsequently selected to investigate the antitumor
      mechanism of these synthetic compounds. The cell cycle results demonstrated that
      CA-4E induced time- and dose-dependent G2/M arrest in a similar manner to CA-4,
      although its effect was more powerful than that of CA-4, and the apoptosis data
      showed that CA-4E induced cellular apoptosis in a dose-dependent manner.
      CONCLUSIONS: The newly synthesized CA-4 derivatives exhibited good antitumor
      activities in vitro, with CA-4E, in particular, showing the highest bioactivity
      of all of the compounds tested. Furthermore, CA-4E induced time- and dose
      dependent G2/M arrest and cellular apoptosis in a dose-dependent manner. Taken
      together, these results suggest that CA-4E should be subjected to further
      investigation as a potential anticancer drug candidate.

PMID- 24304593
TI  - The use of bipolar electrocautery in adult epistaxis management: using audit of
      one hundred and twenty-four cases to define a standardised protocol.

PMID- 24304594
TI  - Rise of intraocular pressure in a caffeine test versus the water drinking test in
      patients with glaucoma.
AB  - BACKGROUND: There is increasing emphasis on the importance of intraocular
      pressure peaks and fluctuations as risk factors for glaucoma progression. It is
      well recognized that the water drinking test raises intraocular pressure and
      there is reasonable evidence that caffeine can also raise intraocular pressure.
      The aim of this study is to directly compare the effect of a caffeine test to
      that of the water drinking test on intraocular pressure, in patients with
      glaucoma. DESIGN: Prospective, observer-masked, cross-over study. PARTICIPANTS:
      Fourteen eyes of 14 patients with primary open-angle glaucoma. METHODS: Patients
      were initially randomized to either caffeine test or water drinking test.
      Intraocular pressure was measured in both eyes with a Goldmann applanation
      tonometer at baseline and every 15 min for 1 h, by a masked examiner. This was
      repeated the following week at the same time of day for the other test (the cross
      over). Peak intraocular pressure and maximum fluctuation from baseline were
      compared between groups using paired t-tests. MAIN OUTCOME MEASURES: Peak and
      fluctuation of intraocular pressure, time of maximum frequency of peak
      intraocular pressure. RESULTS: The maximum intraocular pressure from the water
      drinking test (19.7 +/- 4.1) was greater than the caffeine test (16.7 +/- 4.1)
      and showed greater fluctuation in intraocular pressure (4.3 +/- 2.7 mmHg [27.7%];
      P < 0.0001) compared with the caffeine test (1.8 +/- 1.9 mmHg [11.7%]); P =
      0.004). CONCLUSION: The rise in intraocular pressure was greater with water
      drinking test than the caffeine test. Caffeine does not appear to provide an
      alternative for patients unable to tolerate the water drinking test.

PMID- 24304595
TI  - Osteocalcin increase after bariatric surgery predicts androgen recovery in
      hypogonadal obese males.
AB  - OBJECTIVE: Bone modulates testis function through osteocalcin (OCN) production.
      This paper assesses the association between serum OCN and androgen production
      recovery in morbidly obese males at 9 months after bariatric surgery. SUBJECTS: A
      cohort of n=103 obese males with mean+/-s.d. body mass index (BMI) 47.7+/-8.2 kg
      m(-2), age 42+/-11 years, consisting of n=76 patients undergoing gastric bypass
      and n=27 in the waiting list for surgery. RESULTS: At 9 months from surgery, a
      significant increase was observed in mean+/-s.d. total OCN (tOCN=10.4+/-10.3 ng
      ml(-1), P<0.001) and undercarboxylated OCN (ucOCN=5.4+/-3.7 ng ml(-1), P<0.001),
      total testosterone (TT, 5.6+/-6.5 nM, P<0.001) and calculated free testosterone
      (cFT, 0.035+/-0.133 nM, P<0.006), sex hormone binding globulin (SHBG, 21.2+/-16.7
      nM, P<0.001) and decrease in estradiol (E2, -30.1+/-51.9 pM, P<0.001) levels only
      in operated patients, with a significant reduction in BMI (24%) and waist (20%).
      A positive correlation existed between tOCN and ucOCN (age-adjustment (age-adj.):
      beta=0.692, P<0.001) and their variations (age-adj.: beta=0.629, P<0.001) after
      surgery. Multivariate analysis in operated patients showed a significant positive
      association between variations in tOCN and TT (age-adj.: beta=0.289, P=0.012),
      SHBG (age-adj.: beta=0.326, P=0.005) but not with cFT variation. tOCN, but not
      luteinizing hormone (LH) variation was the only significant predictive factor of
      cFT recovery in the hypogonadal (TT<12 nM) operated subjects even after age- and
      BMI-adjustment (adj.: beta=0.582, P<0.05). cFT improvement was significantly
      higher when considering operated patients with tOCN increase (0.045+/-0.123 vs 
      0.02+/-0.118 nM, P=0.015), hypogonadism (0.059+/-0.111 vs -0.059+/-0.138 nM,
      P=0.002) and younger than 35 years (0.102+/-0.108 vs -0.019+/-0.123 nM, P=0.009).
      CONCLUSION: OCN recovery observed after bariatric surgery is significantly
      associated with cFT improvement independently of BMI variation and age in
      hypogonadal morbidly obese males.

PMID- 24304597
TI  - The ABC of health care team dynamics: understanding complex affective,
      behavioral, and cognitive dynamics in interprofessional teams.
AB  - BACKGROUND: Interprofessional teams form the basis of many health care problem
      solving and decision-making mechanisms. However, more than 70% of medical errors
      are attributable to dysfunctional team dynamics. The recent suggestion that
      health care teams are more complex than nonmedical teams suggests that we require
      more sophisticated knowledge of team dynamics and processes. PURPOSES: The
      mechanisms of dysfunctional interprofessional teams focusing on affective,
      behavioral, and cognitive effects are explored. We argue that interprofessional
      composition impacts team dynamics by increasing the likelihood of affective
      conflict, which mediates a decrease in elaborative behaviors and open-mindedness.
      METHODOLOGY: The hypotheses are investigated using a cross-sectional,
      correlational design. Survey data received from 218 members of 47
      interprofessional teams employed in an acute care setting, representing a 39%
      response rate, is used to investigate two moderated mediation pathways. FINDINGS:
      Analysis supports a significant relationship between interprofessional
      composition and affective conflict but only when team rate highly for
      professional identification. Results also support a dual moderated mediation
      pathway through which professional diversity has a dysfunctional effect on debate
      and open-mindedness. PRACTICE IMPLICATIONS: A range of strategies emerge from the
      findings to minimize dysfunctional interprofessional team dynamics. These include
      the use of leadership strategies, such as transformational styles, reinforcement
      of shared values such as patient-centeredness, and development of a shared group
      identity.

PMID- 24304596
TI  - Fatness predicts decreased physical activity and increased sedentary time, but
      not vice versa: support from a longitudinal study in 8- to 11-year-old children.
AB  - OBJECTIVE: To examine independent and combined cross-sectional associations
      between movement behaviors (physical activity (PA), sedentary time, sleep
      duration, screen time and sleep disturbance) and fat mass index (FMI), as well as
      to examine longitudinal associations between movement behaviors and FMI. METHODS:
      Cross-sectional and longitudinal analyses were done using data from the OPUS
      school meal study on 785 children (52% boys, 13.4% overweight, ages 8-11 years).
      Total PA, moderate-to-vigorous PA (MVPA), sedentary time and sleep duration (7
      days and 8 nights) were assessed by an accelerometer and FMI was determined by
      dual-energy X-ray absorptiometry (DXA) on three occasions over 200 days.
      Demographic characteristics, screen time and sleep disturbance (Children's Sleep
      Habits Questionnaire) were also obtained. RESULTS: Total PA, MVPA and sleep
      duration were negatively associated with FMI, while sedentary time and sleep
      disturbances were positively associated with FMI (P?0.01). However, only total
      PA, MVPA and sleep duration were independently associated with FMI after
      adjustment for multiple covariates (P<0.001). Nevertheless, combined associations
      revealed synergistic effects among the different movement behaviors. Changes over
      time in MVPA were negatively associated with changes in FMI (P<0.001). However,
      none of the movement behaviors at baseline predicted changes in FMI (P>0.05), but
      higher FMI at baseline predicted a decrease in total PA and MVPA, and an increase
      in sedentary time (P?0.001), even in normal-weight children (P?0.03). CONCLUSION:
      Total PA, MVPA and sleep duration were independently associated with FMI, and
      combined associations of movement behaviors showed a synergistic effect with FMI.
      In the longitudinal study design, a high FMI at baseline was associated with
      lower PA and higher sedentary time after 200 days but not vice versa, even in
      normal-weight children. Our results suggest that adiposity is a better predictor
      of PA and sedentary behavior changes than the other way around.

PMID- 24304598
TI  - Childhood arterial ischaemic stroke incidence, presenting features, and risk
      factors: a prospective population-based study.
AB  - BACKGROUND: Arterial ischaemic stroke is an important cause of acquired brain
      injury in children. Few prospective population-based studies of childhood
      arterial ischaemic stroke have been undertaken. We aimed to investigate the
      epidemiology and clinical features of childhood arterial ischaemic stroke in a
      population-based cohort. METHODS: Children aged 29 days to less than 16 years
      with radiologically confirmed arterial ischaemic stroke occurring over a 1-year
      period (July 1, 2008, to June 30, 2009) residing in southern England (population
      denominator 5.99 million children) were eligible for inclusion. Cases were
      identified using several sources (paediatric neurologists and trainees, the
      British Paediatric Neurology Surveillance Unit, paediatricians, radiologists,
      physiotherapists, neurosurgeons, parents, and the Paediatric Intensive Care Audit
      Network). Cases were confirmed by personal examination of cases and case notes.
      Details of presenting features, risk factors, and investigations for risk factors
      were recorded by analysis of case notes. Capture-recapture analysis was used to
      estimate completeness of ascertainment. FINDINGS: We identified 96 cases of
      arterial ischaemic stroke. The crude incidence of childhood arterial ischaemic
      stroke was 1.60 per 100 000 per year (95% CI 1.30-1.96). Capture-recapture
      analysis suggested that case ascertainment was 89% (95% CI 77-97) complete. The
      incidence of arterial ischaemic stroke was highest in children aged under 1 year
      (4.14 per 100 000 per year, 95% CI 2.36-6.72). There was no difference in the
      risk of arterial ischaemic stroke between sexes (crude incidence 1.60 per 100 000
      per year [95% CI 1.18-2.12] for boys and 1.61 per 100 000 per year [1.18-2.14]
      for girls). Asian (relative risk 2.14, 95% CI 1.11-3.85; p=0.017) and black
      (2.28, 1.00-4.60; p=0.034) children were at higher risk of arterial ischaemic
      stroke than were white children. 82 (85%) children had focal features (most
      commonly hemiparesis) at presentation. Seizures were more common in younger
      children (<=1 year) and headache was more common in older children (>5 years;
      p<0.0001). At least one risk factor for childhood arterial ischaemic stroke was
      identified in 80 (83%) cases. INTERPRETATION: Age and racial group, but not sex,
      affected the risk of arterial ischaemic stroke in children. Investigation of such
      differences might provide causative insights. FUNDING: The Stroke Association,
      UK.

PMID- 24304599
TI  - A global survey of changing patterns of food allergy burden in children.
AB  - While food allergies and eczema are among the most common chronic non
      communicable diseases in children in many countries worldwide, quality data on
      the burden of these diseases is lacking, particularly in developing countries.
      This 2012 survey was performed to collect information on existing data on the
      global patterns and prevalence of food allergy by surveying all the national
      member societies of the World Allergy Organization, and some of their
      neighbouring countries. Data were collected from 89 countries, including
      published data, and changes in the health care burden of food allergy. More than
      half of the countries surveyed (52/89) did not have any data on food allergy
      prevalence. Only 10% (9/89) of countries had accurate food allergy prevalence
      data, based on oral food challenges (OFC). The remaining countries (23/89) had
      data largely based on parent-reporting of a food allergy diagnosis or symptoms,
      which is recognised to overestimate the prevalence of food allergy. Based on more
      accurate measures, the prevalence of clinical (OFC proven) food allergy in
      preschool children in developed countries is now as high as 10%. In large and
      rapidly emerging societies of Asia, such as China, where there are documented
      increases in food allergy, the prevalence of OFC-proven food allergy is now
      around 7% in pre-schoolers, comparable to the reported prevalence in European
      regions. While food allergy appears to be increasing in both developed and
      developing countries in the last 10-15 years, there is a lack of quality
      comparative data. This survey also highlights inequities in paediatric allergy
      services, availability of adrenaline auto-injectors and standardised National
      Anaphylaxis Action plans. In conclusion, there remains a need to gather more
      accurate data on the prevalence of food allergy in many developed and developing
      countries to better anticipate and address the rising community and health
      service burden of food allergy. 

PMID- 24304600
TI  - Genome-wide and local pattern of linkage disequilibrium and persistence of phase
      for 3 Danish pig breeds.
AB  - BACKGROUND: The extent of linkage disequilibrium (LD) is of critical importance
      for genomic selection and marker assisted selection. The primary purpose of this
      study is to examine patterns of LD in three Danish pig breeds (Duroc, Landrace
      and Yorkshire); we also examine patterns of persistence of phase between the
      breeds. We quantify local LD by fitting a model relating LD to physical distance
      between markers in sliding windows, and use this to visualize how LD varies
      according to physical position. We use a similar method to examine local
      persistence of phase. RESULTS: Average LD decay over distance for Duroc was
      significantly different from Landrace and Yorkshire, that showed similar
      patterns. Persistence of phase between Landrace and Yorkshire was much higher
      than between these breeds and Duroc. Local r2 over the chromosomes showed more
      variation between breeds than average r2 decay across whole genome. Also local
      persistence of phase was higher between Landrace and Yorkshire than between these
      breeds and Duroc. CONCLUSIONS: The results concerning genome-wide LD indicated
      that Duroc had "old inbreeding", and confirmed the mixture history of Landrace
      and Yorkshire, which is also implied by the higher level of persistence of phase
      between Landrace and Yorkshire. The method to estimate and visualize local
      pattern of LD and persistence of phase provides insight into how these quantities
      vary along chromosomes and between breeds.

PMID- 24304601
TI  - [Activation of cerebellar B-type gamma-aminobutyric acid receptor modulates
      optokinetic reflex adaptation].
AB  - The cerebellar cortex, the brain region responsible for motor coordination and
      learning expresses a high density of B-type gamma-aminobutyric acid receptor
      (GABAbR). Previous in vitro and in situ studies indicated that cerebellar GABAbR
      may mediate multiple forms of inhibitory and excitatory modulation of cerebellar
      circuits. Nevertheless, the in vivo influence of cerebellar GABAbR activation is
      unclear. As the first step in addressing this issue, we examined how
      pharmacological activation of cerebellar GABAbR modulates optokinetic reflex
      (OKR), an involuntary cerebellum-dependent eye movement for stabilizing the
      retinal image against the drift of the visual scene. We injected baclofen, a
      GABAbR-selective agonist, or control saline into the cerebellar flocculi of adult
      mice and then performed 1-h OKR measurement sessions on two consecutive days. In
      the day 1 session, the baclofen (5 nM)-injected mice and control mice showed
      similar initial OKR gains and similar training-induced increases in the OKR gain
      (OKR adaptation). This result suggests that GABAbR activation does not affect
      cerebellar computation for executing OKR and formation of short-term memory for
      OKR adaptation. At the beginning of the day 2 session, the baclofen (5 nM or 50
      MUM)-injected mice showed an OKR gain higher than that achieved in the day 1
      session while the control mice did not. This result suggests that GABAbR
      activation may facilitate the formation of OKR adaptation-related long-term
      memory. These findings provide a new insight into the functional architecture of
      the cerebellar circuits and indicate GABAbR to be a new target of pharmacological
      therapy against diseases with cerebellar dysfunction.

PMID- 24304602
TI  - Effect of patient safety strategies on the incidence of adverse events.
AB  - OBJECTIVE: This study aims to estimate the incidence of adverse events (AEs) and
      avoidable AE in four hospital services before and after applying strategies for
      patient safety. DESIGN: Retrospective study of two cohorts (2006 and 2009).
      SETTING: General Surgery, Internal Medicine, Intensive Care Unit and Oncology
      services. PARTICIPANTS: A sample of 365 patients (2006) and 232 in 2009 randomly
      selected from the services previously cited. INTERVENTIONS: Strategies to improve
      patient safety (e.g. hand-hygiene campaign). MAIN OUTCOME MEASURES: Analyses were
      made of the change in the incidence and type of AE and avoidable AE, number of
      procedures and additional days of hospital stay, and the concordance between two
      recording systems. RESULTS: The incidence of patients with AE was 20.8% in 2006
      compared with 28.9% in 2009 (P < 0.05). Oncology had twofold more AE than did
      General Surgery [odds ratio (OR) = 2.07, 95% confidence interval (CI): 1.12-3.86]
      for the same length of stay and number of extrinsic risk factors. In 2006, 84.6%
      were considered avoidable, compared with 57.1% of 2009 (P < 0.001). There was no
      difference in the average length of additional stay. In 2006, there were more
      additional procedures compared to 2009 (OR = 2.75, 95% CI: 1.28-6.06). A
      concordance of 61% was found for the detection of AE with the two recording
      systems. CONCLUSIONS: An increased incidence in AEs was found after the
      strategies, while avoidable AE decreased, as did additional treatments and
      procedures. The measures implemented constitute a further step in reducing
      avoidance and a greater awareness of recording AEs in the discharge report.

PMID- 24304603
TI  - Cloning and characterization of a potato StAN11 gene involved in anthocyanin
      biosynthesis regulation.
AB  - Anthocyanins are a class of products of plant secondary metabolism and are
      responsible for tubers color in potato. The biosynthesis of anthocyanins is a
      complex biological process, in which multiple genes are involved including
      structural genes and regulatory genes. In this study, StAN11, a WD40-repeat gene,
      was cloned from potato cultivar Chieftain (Solanum tuberosum L.). StAN11
      (HQ599506) contained no intron and its open reading frame (ORF) was 1,029 bp
      long, encoding a putative protein of 342 amino acids. In order to verify its role
      in anthocyanin biosynthesis, StAN11 was inserted behind the CaMV-35S promoter of
      pCMBIA1304 and the recombination vector was introduced into the potato cultivar
      Desiree plants by Agrobacterium-mediated transformation. The color of transgenic
      tuber skin was significantly deepened, compared to the wild-type control, which
      was highly consistent with the accumulation of anthocyanin and expression of
      StAN11 in transgenic lines tuber skin. Further analysis on the expression of
      Flavonone-3-hydroxylase (F3H), Dihydroflavonol reductase (DFR), Anthocyanidin
      synthase (ANS), and Flavonoid 3-O-glucosyl transferase (3GT) in transgenic plants
      revealed that only DFR was upregulated. This result suggested that StAN11
      regulated anthocyanin biosynthesis in potato by controlling DFR expression and
      accumulation of anthocyanin could be increased through overexpression of StAN11
      in the tubers with the genetic background of anthocyanin biosynthesis. 

PMID- 24304604
TI  - Organization of protein complexes under photomorphogenic UV-B in Arabidopsis.
AB  - Low-fluence and long-wavelength UV-B (UV-B) light promotes photomorphogenic
      development in Arabidopsis. CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) is a positive
      regulator in this pathway while it is a negative regulator of the traditional
      photomorphogenesis triggered by far-red and visible light. We have recently
      reported the mechanism by which the switch of COP1 function is accomplished in
      distinct light contexts. In response to photomorphogenic UV-B, the photoactivated
      UV RESISTANCE LOCUS 8 (UVR8) associates with the COP1- SUPRESSOR OF PHYA (SPA)
      core complexes, resulting in the physical and functional disassociation of COP1
      SPA from the CULLIN4-DAMAGED DNA BINDING PROTEIN 1 (CUL4-DDB1) E3 scaffold. These
      UV-B dependent UVR8-COP1-SPA complexes promote the stability and activity of
      ELONGATED HYPOCOTYL 5 (HY5), and eventually cause COP1 to switch from repressing
      to promoting photomorphogenesis. In addition, it is possible that CUL4-DDB1 might
      simultaneously recruit alternative DDB1 BINDING WD40 (DWD) proteins to repress
      this UV-B-specific signaling. Further investigation is required, however, to
      verify this hypothesis. Overall, the coordinated organization of various protein
      complexes facilitates an efficient and balanced UV-B signaling. 

PMID- 24304605
TI  - Enhanced increase of omega-3 index in healthy individuals with response to 4-week
      n-3 fatty acid supplementation from krill oil versus fish oil.
AB  - BACKGROUND: Due to structural differences, bioavailability of krill oil, a
      phospholipid based oil, could be higher than fish oil, a triglyceride-based oil,
      conferring properties that render it more effective than fish oil in increasing
      omega-3 index and thereby, reducing cardiovascular disease (CVD) risk. OBJECTIVE:
      The objective was to assess the effects of krill oil compared with fish oil or a
      placebo control on plasma and red blood cell (RBC) fatty acid profile in healthy
      volunteers. PARTICIPANTS AND METHODS: Twenty four healthy volunteers were
      recruited for a double blinded, randomized, placebo-controlled, crossover trial.
      The study consisted of three treatment phases including krill or fish oil each
      providing 600 mg of n-3 polyunsaturated fatty acids (PUFA) or placebo control,
      corn oil in capsule form. Each treatment lasted 4 wk and was separated by 8 wk
      washout phases. RESULTS: Krill oil consumption increased plasma (p = 0.0043) and
      RBC (p = 0.0011) n-3 PUFA concentrations, including EPA and DHA, and reduced n
      6:n-3 PUFA ratios (plasma: p = 0.0043, RBC: p = 0.0143) compared with fish oil
      consumption. Sum of EPA and DHA concentrations in RBC, the omega-3 index, was
      increased following krill oil supplementation compared with fish oil (p = 0.0143)
      and control (p < 0.0001). Serum triglycerides and HDL cholesterol concentrations
      did not change with any of the treatments. However, total and LDL cholesterol
      concentrations were increased following krill (TC: p = 0.0067, LDL: p = 0.0143)
      and fish oil supplementation (TC: p = 0.0028, LDL: p = 0.0143) compared with
      control. CONCLUSIONS: Consumption of krill oil was well tolerated with no adverse
      events. Results indicate that krill oil could be more effective than fish oil in
      increasing n-3 PUFA, reducing n-6:n-3 PUFA ratio, and improving the omega-3
      index. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01323036.

PMID- 24304606
TI  - Stable HIV-1 integrase diversity during initial HIV-1 RNA decay suggests complete
      blockade of plasma HIV-1 replication by effective raltegravir-containing salvage
      therapy.
AB  - BACKGROUND: There is legitimate concern that minority drug-resistant mutants may
      be selected during the initial HIV-1 RNA decay phase following antiretroviral
      therapy initiation, thus undermining efficacy of treatment. The goal of this
      study was to characterize viral resistance emergence and address viral population
      evolution during the first phase of viral decay after treatment containing
      initiation. FINDINGS: 454 sequencing was used to characterize viral genetic
      diversity and polymorphism composition of the HIV-1 integrase gene during the
      first two weeks following initiation of raltegravir-containing HAART in four ART
      experienced subjects. No low-prevalence Raltegravir (RAL) drug resistance
      mutations (DRM) were found at baseline. All patients undergoing treatment
      received a fully active ART according to GSS values (GSS >= 3.5). No emergence of
      DRM after treatment initiation was detected. Longitudinal analysis showed no
      evidence of any other polymorphic mutation emergence or variation in viral
      diversity indexes. CONCLUSIONS: This suggests that fully active salvage
      antiretroviral therapy including raltegravir achieves a complete blockade of HIV
      1 replication in plasma. It is unlikely that raltegravir-resistant HIV-1 may be
      selected in plasma during the early HIV-1 RNA decay after treatment initiation if
      the administered therapy is active enough.

PMID- 24304607
TI  - Detection limit of intragenic deletions with targeted array comparative genomic
      hybridization.
AB  - BACKGROUND: Pathogenic mutations range from single nucleotide changes to
      deletions or duplications that encompass a single exon to several genes. The use
      of gene-centric high-density array comparative genomic hybridization (aCGH) has
      revolutionized the detection of intragenic copy number variations. We implemented
      an exon-centric design of high-resolution aCGH to detect single- and multi-exon
      deletions and duplications in a large set of genes using the OGT 60 K and 180 K
      arrays. Here we describe the molecular characterization and breakpoint mapping of
      deletions at the smaller end of the detectable range in several genes using aCGH.
      RESULTS: The method initially implemented to detect single to multiple exon
      deletions, was able to detect deletions much smaller than anticipated. The
      selected deletions we describe vary in size, ranging from over 2 kb to as small
      as 12 base pairs. The smallest of these deletions are only detectable after
      careful manual review during data analysis. Suspected deletions smaller than the
      detection size for which the method was optimized, were rigorously followed up
      and confirmed with PCR-based investigations to uncover the true detection size
      limit of intragenic deletions with this technology. False-positive deletion calls
      often demonstrated single nucleotide changes or an insertion causing lower
      hybridization of probes demonstrating the sensitivity of aCGH. CONCLUSIONS: With
      optimizing aCGH design and careful review process, aCGH can uncover intragenic
      deletions as small as dozen bases. These data provide insight that will help
      optimize probe coverage in array design and illustrate the true assay
      sensitivity. Mapping of the breakpoints confirms smaller deletions and
      contributes to the understanding of the mechanism behind these events. Our
      knowledge of the mutation spectra of several genes can be expected to change as
      previously unrecognized intragenic deletions are uncovered.

PMID- 24304608
TI  - Factors associated with adherence to the Mediterranean diet among adolescents
      living in Sicily, Southern Italy.
AB  - The present study aimed to examine the factors associated with increased
      Mediterranean diet (MD) adherence among a sample of Italian adolescents. A cross
      sectional survey was conducted on 1135 students (13-16 years) attending 13
      secondary schools of Sicily, southern Italy. Validated instruments were used for
      dietary assessment and the KIDMED score to assess adolescents' adherence to the
      MD. A higher adherence to the MD was associated with high socioeconomic status
      (Odds Ratio [OR] 1.53, 95% Confidence Interval [CI]: 1.03-2.26) and high physical
      activity (OR 1.19, 95% CI: 1.02-1.70), whereas lower adherence was associated
      with living in an urban environment (OR 0.65, 95% CI: 0.44-0.97) and being obese
      (OR 0.59, 95% CI: 0.37-0.94). The adolescents' KIDMED scores were inversely
      associated with adolescents' intake of sweets, fast foods, fried foods, and
      sugary drinks, and directly with fruit, vegetables, pasta, fish, and cheese
      intakes. Urban-living adolescents were less likely to eat fruit and more prone to
      consume meat, sugary drinks, and fast food than rural-living adolescents. The
      latter were more likely to eat sweets and snacks. A general poor quality of food
      consumption in Italian adolescents away from the MD was reported, especially
      among those living in urban areas. 

PMID- 24304609
TI  - Hormonal relationships to bone mass in elderly Spanish men as influenced by
      dietary calcium and vitamin D.
AB  - We aim to evaluate whether calcium and vitamin D intake is associated with 25
      hydroxyvitamin D (25-OH-Vitamin D3) and parathyroid hormone (PTH) serum
      concentrations or is associated with either the phalangeal dual energy X-ray
      absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent
      elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly
      men (mean age: 73.31 +/- 5.10 year). Food intake was quantified using a dietetic
      scale. Participants with 25-OH-Vitamin D3 levels >= 30 ng/mL (75 nmol/L) and a
      calcium intake of 800-1200 mg/day exhibited the lowest PTH levels (41.49 +/-
      16.72 ng/mL). The highest PTH levels (75.60 +/- 14.16 ng/mL) were observed in the
      <30 ng/mL group 25-OH-Vitamin D3 with a calcium intake >1200 mg/day. No
      significant differences in the serum PTH levels based on the serum 25-OH-Vitamin
      D3 levels were observed among participants with a calcium intake of 800-1200
      mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D3 in the
      entire patient sample (r = -0.288, p = 0.019). No differences in any of the three
      densitometry techniques were observed between any of the age groups in the 800
      1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate
      negatively with serum 25-OH-Vitamin D3 levels, and neither calcium nor vitamin D
      intake exert a strong influence on either of the two parameters. 

PMID- 24304610
TI  - Adult cranberry beverage consumers have healthier macronutrient intakes and
      measures of body composition compared to non-consumers: National Health and
      Nutrition Examination Survey (NHANES) 2005-2008.
AB  - Flavonoids, present in high levels in cranberries, are potent bioactives known
      for their health-promoting benefits, but cranberry beverages (CB) are not
      typically recommended as part of a healthy diet. We examine the association
      between CB consumption with macronutrient intake and weight status. Data for US
      adults (>=19 years, n = 10,891) were taken from the National Health and Nutrition
      Examination Survey (NHANES) Survey 2005-2008. Total CB consumption was measured
      over two non-consecutive 24-h dietary recalls. Linear and logistic regression
      models adjusting for important covariates were used to examine predicted
      differences between CB consumers and non-consumers on macronutrient and
      anthropometric outcomes. Results are weighted to be nationally representative. CB
      consumers (n = 581) were older (>50 year) non-Hispanic black females. They
      consumed an average 221 mL (7.5 oz) CB per day. In fully adjusted models CB
      consumers (vs. non-consumers) had higher carbohydrates and total sugars and lower
      percent energy from protein and total fat (all p < 0.001), but no difference in
      total energy. A significantly higher proportion of CB consumers were predicted to
      be normal weight (BMI < 25 kg/m2; p = 0.001) and had to have lower waist
      circumferences (p = 0.001). Although there was not a significant trend across
      level of CB intake, low and middle level CB consumers compared to non-consumers
      were more likely to be normal weight (p < 0.001) and less likely to be
      overweight/obese (BMI >= 25 kg/m2, p < 0.001). Despite having slightly higher
      daily macronutrient intakes, CB consumers have more desirable anthropometric
      measures compared to non-consumers. 

PMID- 24304611
TI  - Probiotic supplements.

PMID- 24304613
TI  - Attacks on health workers in conflict areas should be documented for advocacy
      purposes, conference hears.

PMID- 24304614
TI  - Case of Italian mother who underwent forced caesarean is to go to High Court.

PMID- 24304615
TI  - Isotopic composition and identification of the origins of individuals buried in a
      Neolithic collective grave at Bronocice (southern Poland).
AB  - The oxygen present in a human organism comes from numerous sources, but the major
      factor that causes variation in the isotopic composition of this element in a
      tissue is available drinking water. The isotopic ratio of oxygen in an organism's
      tissue, including that found in bones and teeth, reflects the isotopic oxygen
      composition typical for the area where a given individual developed and lived. Of
      particular interest with regard to this issue were a series of skeletons from the
      multiple grave discovered at the Funnel Beaker-Baden settlement at Bronocice
      (southern Poland). The question therefore arose whether the specimens buried in
      this grave were part of the local community. The oxygen isotope level was
      established using apatite isolated from bones or teeth. A femur and root dentine
      samples taken from permanent teeth were subjected to oxygen isotope analysis. The
      oxygen isotope level of the site was established on the basis of local water
      precipitation and measurements taken from the oxygen isotope concentration in
      apatite samples isolated from the bones of animals co-occurring with the studied
      human group. It has been found that the oxygen isotope levels in the bones and
      dentine of almost all the analysed specimens from the excavated site at Bronocice
      were within the established range for the area's environment, providing evidence
      for their local origin. Thus, it can be assumed that the analysed group
      inhabiting the macrosettlement at Bronocice during the Funnel Beaker phase of the
      Baden culture was most probably of local origin. 

PMID- 24304616
TI  - Dendritic cells activated by double-stranded RNA induce arthritis via autocrine
      type I IFN signaling.
AB  - Viral dsRNA can be found at the site of inflammation in RA patients, and intra
      articular injection of dsRNA induces arthritis by activating type I IFN signaling
      in mice. Further, DCs, a major source of IFN-alpha, can be found in the synovium
      of RA patients. We therefore determined the occurrence of DCs in dsRNA-induced
      arthritis and their ability to induce arthritis. Here, we show, by
      immunohistochemistry, that cells expressing the pan-DC marker CD11c and the pDC
      marker 120G8 are present in the inflamed synovium in dsRNA-induced arthritis.
      Flt3L-generated and splenic DCs preactivated with dsRNA before intra-articular
      injection, but not mock-stimulated cells, clearly induced arthritis. Induction of
      arthritis was dependent on type I IFN signaling in the donor DCs, whereas IFNAR
      expression in the recipient was not required. Sorting of the Flt3L-DC population
      into cDCs (CD11c(+), PDCA-1(-)) and pDCs (CD11c(+), PDCA-1(+)) revealed that both
      subtypes were arthritogenic and produced type I IFN if treated with dsRNA. Taken
      together, these results demonstrate that viral nucleic acids can elicit arthritis
      by activating type I IFN signaling in DCs. Once triggered, autocrine type I IFN
      signaling in dsRNA-activated DCs is sufficient to propagate arthritis. 

PMID- 24304617
TI  - Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular
      carcinoma (HCC).
AB  - BACKGROUND: While recent research has shown that expression of ZEB-1 in a variety
      of tumors has a crucial impact on patient survival, there is little information
      regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study
      investigated the co-expression of ZEB-1 and E-cadherin in HCC by
      immunohistochemistry and evaluated its association with clinical factors,
      including patient prognosis. METHODS: A total of 108 patients with primary HCC
      treated by curative hepatectomy were enrolled. ZEB-1 expression was
      immunohistochemically categorized as positive if at least 1% cancer cells
      exhibited nuclear staining. E-cadherin expression was divided into preserved and
      reduced expression groups and correlations between ZEB-1 and E-cadherin
      expression and clinical factors were then evaluated. RESULTS: With respect to ZEB
      1 expression, 23 patients were classified into the positive group and 85 into the
      negative group. Reduced E-cadherin expression was seen in 44 patients and
      preserved expression in the remaining 64 patients. ZEB-1 positivity was
      significantly associated with reduced expression of E-cadherin (p = 0.027).
      Moreover, significant associations were found between ZEB-1 expression and venous
      invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p
      = 0.025). Reduced E-cadherin expression was significantly associated with
      intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients
      with both ZEB-1 positivity and reduced E-cadherin expression had a poorer
      prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a
      significant prognostic factor by multivariate analysis. There was no statistical
      difference in overall survival when E-cadherin expression was reduced in the ZEB
      1 positive group (p = 0.24). CONCLUSIONS: Positive ZEB-1 expression and loss of E
      cadherin expression are correlated with poor prognosis in HCC patients and
      malignancy of ZEB-1 positive tumors involves EMT.

PMID- 24304618
TI  - Awareness of diabetes mellitus among diabetic patients in the Gambia: a strong
      case for health education and promotion.
AB  - BACKGROUND: Awareness of various aspects of Diabetes Mellitus (DM) is essential
      for the prevention, management and control of the disease. However, several
      studies have consistently shown that awareness of DM in the general population is
      low. None of these studies, however, was conducted in The Gambia, even though the
      condition constitutes a major public health problem in the country. In this
      paper, we assessed the awareness of DM among diabetic patients attending the
      Medical Out-Patient Department (MOPD) of Royal Victoria Teaching Hospital (RVTH),
      Banjul. METHODS: We interviewed 200 patients attending the MOPD of RVTH. We used
      a tool containing questions on patient's demographic characteristics and
      awareness of various aspects of DM including general knowledge on DM, causes,
      complications, management and prevention. RESULTS: Of the 199 patients who were
      aware of their condition, only 47% said they knew what DM is. Similarly, 53% of
      the study participants had no knowledge of the causes of DM and about 50% were
      not aware of the methods of prevention. 67% knew that DM can result to loss of
      sight while 46.5% knew that DM can cause poor wound healing. Few respondents knew
      that DM can lead to kidney failure (13.5%), skin sepsis (12.0%), heart failure
      (5.5%) and stroke (4.5%). Close to 50% of the respondent did not know how DM can
      be prevented. Level of education, duration of illness and knowledge of a family
      member with diabetes were important predictors of knowledge in our study.
      CONCLUSION: Our study shows that the majority of patients attending the MOPD have
      poor knowledge on several aspects of DM. Hence, there is need for conscious
      efforts towards improving the level of awareness through health education and
      promotion, not limited to the hospital but also within the general population, as
      part of strategies to prevent, manage and control DM.

PMID- 24304620
TI  - Dipolar interaction in arrays of magnetic nanotubes.
AB  - The dipolar interaction field in arrays of nickel nanotubes has been investigated
      on the basis of expressions derived from the effective demagnetizing field of the
      assembly as well as magnetometry measurements. The model incorporates explicitly
      the wall thickness and aspect ratio, as well as the spatial order of the
      nanotubes. The model and experiment show that the interaction field in nanotubes
      is smaller than that in solid nanowires due to the packing fraction reduction in
      tubes related to their inner cavity. Finally, good agreement between the model
      and experiment is found for the variation of the interaction field as a function
      of the tube wall thickness. 

PMID- 24304619
TI  - RNA interference targeting human integrin alpha6 suppresses the metastasis
      potential of hepatocellular carcinoma cells.
AB  - BACKGROUND: Increased metastasis has been proved to be associated with a poor
      prognosis for hepatocellular carcinoma (HCC). There are higher-level expressions
      of integrin alpha6 in the tissues of HCC patients with a higher fatality rate.
      The aim of this study is to investigate the effect of short hairpin RNA (shRNA)
      silencing integrin alpha6 expression on the proliferation and metastasis in HCC
      cell lines. METHODS: Two human HCC cell lines, HepG2 and Bel-7402 were
      transfected with shRNA targeting human integrin alpha6. Protein and mRNA
      expression level were determined by western blot and real-time quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) to detect the
      transfected efficacy. The metastasis potential of HCC cells was evaluated by
      their proliferation, adhesion and invasion abilities. Cell proliferation was
      measured by MTT assay. Adhesion ability was measured by adhesion and spreading
      assays. The expression of matrix metalloproteinases (MMPs) was measured by qRT
      PCR. The potential of invasion was measured by qRT-PCR and Transwell chamber
      assay. PI3K inhibitor LY294002 was used to explore the signal pathways of
      integrin alpha6 in HCC cells. RESULTS: Western blot and qRT-PCR detection showed
      that over 75% of integrin alpha6 expression in HCC cells was through knockdown by
      shRNA. Proliferation, adhesion, spreading and invasion of HepG2 and Bel-7402
      cells were dramatically decreased in cells transfected with shRNA compared to the
      control cells. P-ERK and p-AKT were reduced by shRNA targeting integrin alpha6
      and PI3K inhibitor LY294002. CONCLUSION: Knockdown integrin alpha6 can inhibit
      the proliferation and metastasis of HCC cells through PI3K/ARK and MAPK/ERK
      signal pathways by shRNA in vitro. Integrin alpha6 can mediate the metastasis
      potential, and can be used as a candidate target for therapy in HCC resulting in
      improved patients' survival.

PMID- 24304621
TI  - Influence of family history on survival in patients with colon and rectal cancer.
AB  - OBJECTIVE: We aimed to investigate the association between a family history (FH)
      of colorectal cancer (CRC) and cancer recurrence and survival in patients with
      stage III CRC. METHODS: From April 2001 to December 2007, 1102 patients with
      stage III CRC were enrolled and their data including FH, clinicopathological
      characteristics of the tumor were retrospectively analyzed. RESULTS: Of 971
      patients that were finally enrolled, 63 (6.5%) reported CRC in at least one first
      degree relative. Death occurred in 12.7% of the CRC patients with an FH and 21.8%
      in those without an FH. A multivariate analysis showed that patients with an FH
      of CRC, compared with those without FH, had an adjusted hazard ratios (HR) of
      0.674 (P = 0.281) for overall survival (OS) and 0.672 (P = 0.220) for disease
      free survival (DFS). However, the location of tumor, preoperative
      carcinoembryonic antigen (CEA) level, tumor invasion (T) stage and lymph node (N)
      metastasis significantly affected OS and DFS. Furthermore, whereas the FH of CRC
      patients was associated with a favorable prognosis in stage III colon cancer (HR
      0.224, P = 0.040) but not in rectal cancer (HR 1.225, P = 0.640). CONCLUSIONS: In
      patients with stage III CRC, tumor location (especially in the rectum), a high
      preoperative CEA level and advanced T and N stages indicate a poor prognosis.
      However, in stage III colon cancer FH is associated with improved survival.

PMID- 24304622
TI  - Left ventricular strain distribution in healthy dogs and in dogs with tachycardia
      induced dilated cardiomyopathy.
AB  - BACKGROUND: Recently, left ventricular (LV) strain distribution pattern has been
      assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy
      (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in
      terms of global LV dysfunction but with poor understanding of regional
      variability in LV function. We hypothesized that TIC induces specific changes in
      LV strain distribution pattern. METHODS: Twenty five adult mongrel conscious dogs
      were trained to lie down calmly for echocardiography. In seven selected dogs, we
      implanted pacing system for TIC induction under general anesthesia. We measured
      LV geometry and function, strains, and torsion before and after the development
      of TIC in awake non-sedated state. RESULTS: In 25 healthy dogs, all three types
      of normal strain significantly increased from base to apex (p <0.05), while a
      definite and recognizable twist could be measured due to presence of shear
      strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout
      the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05),
      and negative peak twist rate (p <0.05). Interestingly, the relative decrease of
      strain due to TIC was more pronounced in the apex (p < 0.001), with the radial
      strain decreasing the most (p < 0.05). CONCLUSION: TIC is accompanied by
      decreased systolic LV strain and twist deformation, as well as loss of early
      diastolic recoil. In addition, the decrease of strain was more profound in the
      apex. This "reverse" distribution of LV strain may help us understand LV
      dysfunction in the presence of nonischemic etiology.

PMID- 24304623
TI  - Analgesic tolerance of opioid agonists in mutant mu-opioid receptors expressed in
      sensory neurons following intrathecal plasmid gene delivery.
AB  - BACKGROUND: Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs)
      are known to play critical roles in the receptor functions. Our understanding of
      their participation in opioid analgesia is mostly based on studies of opioid
      effects on mutant receptors expressed in in vitro preparations, including cell
      lines, isolated neurons and brain slices. The behavioral consequences of the
      mutation have not been fully explored due to the complexity in studies of mutant
      receptors in vivo. To facilitate the determination of the contribution of
      phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed
      mutant and wild-type human MORs (hMORs) in sensory dorsal root ganglion (DRG)
      neurons, a major site for nociceptive (pain) signaling and determined morphine-
      and the full MOR agonist, DAMGO,-induced effects on heat-induced hyperalgesic
      behaviors and potassium current (IK) desensitization in these rats. FINDINGS: A
      mutant hMOR DNA with the putative phosphorylation threonine site at position 394
      replaced by an alanine (T394A), i.e., hMOR-T, or a plasmid containing wild type
      hMOR (as a positive control) was intrathecally delivered. The plasmid containing
      GFP or saline was used as the negative control. To limit the expression of
      exogenous DNA to neurons of DRGs, a neuron-specific promoter was included in the
      plasmid. Following a plasmid injection, hMOR-T or hMOR receptors were expressed
      in small and medium DRG neurons. Compared with saline or GFP rats, the analgesic
      potency of morphine was increased to a similar extent in hMOR-T and hMOR rats.
      Morphine induced minimum IK desensitization in both rat groups. In contrast,
      DAMGO increased analgesic potency and elicited IK desensitization to a
      significantly less extent in hMOR-T than in hMOR rats. The development and extent
      of acute and chronic tolerance induced by repeated morphine or DAMGO applications
      were not altered by the T394A mutation. CONCLUSIONS: These results indicate that
      phosphorylation of T394 plays a critical role in determining the potency of DAMGO
      induced analgesia and IK desensitization, but has limited effect on morphine
      induced responses. On the other hand, the mutation contributes minimally to both
      DAMGO- and morphine-induced behavioral tolerance. Furthermore, the study shows
      that plasmid gene delivery of mutant receptors to DRG neurons is a useful
      strategy to explore nociceptive behavioral consequences of the mutation.

PMID- 24304624
TI  - Building immunity against interpersonal stress: the holistic way.

PMID- 24304625
TI  - Design thinking.

PMID- 24304626
TI  - Reflexology: its effects on physiological anxiety signs and sedation needs.
AB  - To investigate whether reflexology has an effect on the physiological signs of
      anxiety and level of sedation in patients receiving mechanically ventilated
      support, a single blinded, randomized controlled design with repeated measures
      was used in the intensive care unit of a university hospital in Turkey. Patients
      (n = 60) aged between 18 and 70 years and were hospitalized in the intensive care
      unit and receiving mechanically ventilated support. Participants were randomized
      to a control group or an intervention group. The latter received 30 minutes of
      reflexology therapy on their feet, hands, and ears for 5 days. Subjects had vital
      signs taken immediately before the intervention and at the 10th, 20th, and 30th
      minutes of the intervention. In the collection of the data, "American Association
      of Critical-Care Nurses Sedation Assessment Scale" was used. The reflexology
      therapy group had a significantly lower heart rate, systolic blood pressure,
      diastolic blood pressure, and respiratory rate than the control group. A
      statistically significant difference was found between the averages of the scores
      that the patients included in the experimental and control groups received from
      the agitation, anxiety, sleep, and patient-ventilator synchrony subscales of the
      American Association of Critical-Care Nurses Sedation Assessment Scale.
      Reflexology can serve as an effective method of decreasing the physiological
      signs of anxiety and the required level of sedation in patients receiving
      mechanically ventilated support. Nurses who have appropriate training and
      certification may include reflexology in routine care to reduce the physiological
      signs of anxiety of patients receiving mechanical ventilation. 

PMID- 24304627
TI  - Beliefs about preventive care, individual health, and lifestyle change among low
      income African American women at risk for diabetes.
AB  - Focus groups were held to better understand conceptions of disease prevention
      among low-income African American women at risk for diabetes. Mental calm was
      associated with health more than nutrition, exercise, or social connection. This
      finding suggests that prioritizing stress reduction will help with successful
      implementation of community holistic diabetes prevention programs. 

PMID- 24304628
TI  - Critical care nurses' understanding of the concept of patient-centered care in
      Iran: a qualitative study.
AB  - This study explores the perception of nurses working in critical care units about
      the patient-centered care, which is a crucial factor in attaining quality in
      nursing care. A qualitative exploratory study with conventional content analysis
      was used. Three main themes were extracted from the data: from accepting to
      understanding the patient; improved care as the result of skill and expertise;
      and adherence to patients' rights charter. 

PMID- 24304629
TI  - Use of music in the treatment of insomnia: a pilot study.
AB  - The purpose of this pilot study was to evaluate the use of music to improve
      quality of sleep. Adults with insomnia listened to music at bedtime for 30 days.
      Measured by the Pittsburg Sleep Quality Index, results indicated that the use of
      music significantly increased sleep quality. 

PMID- 24304630
TI  - Concept mapping: a child health nursing practical exercise.
AB  - Concept mapping is a teaching-learning strategy that can be used to evaluate a
      nursing student's ability to critically think in the clinical setting. Nursing
      students who are committed to patient care, seldom express the ideas of
      reasoning, and critical thinking in health team care. This article is a
      description of an educational innovation that utilizes concept mapping as a
      teaching strategy in the development of critical thinking skills among
      undergraduate nursing students. The purpose of this article was to prepare a
      child health nursing example for concept mapping in the educational programs of
      nursing students. The use of this teaching strategy includes shortening the
      wording and descriptions for each stage of evaluation to promote ease of use for
      the student in the growth of critical thinking skills. 

PMID- 24304631
TI  - The value of peer-led support groups among caregivers of persons with Parkinson's
      disease.
AB  - Many persons with Parkinson's disease are cared for by family members. The strain
      of caregiving can negatively affect the health of the caregiver and affect long
      term care decisions, making caregiver support a priority. This study highlights
      the importance of peer-led support groups for family caregivers of persons with
      Parkinson's disease. 

PMID- 24304632
TI  - Holism and embodiment in nursing: using Goethean science to join 2 perspectives
      on patient care.
AB  - Holism is a central concept in nursing theory, yet recently, embodiment has
      become prominent in the literature. Epistemological foundations from modern and
      contemporary philosophy are discussed and their relationship to nursing practice
      is explored to investigate the concepts of holism and embodiment. Nurses practice
      holistic care within the patient encounter while patients live an embodied
      experience. This creates inherent dissonance in the nurse-patient interaction.
      Goethean science is presented as a way to reconcile this discrepancy, to allow
      the nurse to better understand the patient's embodiment and, by default, his or
      her own embodiment. A new perspective of how nursing practice can use Goethean
      science and an embodied perspective are presented as a means to actualize
      Carper's fundamental pattern of knowing of personal knowledge within the nurse
      patient interaction. With this approach, the nurse is able to examine the
      phenomenon of the patient with the patient to explore the essential nature that
      makes the patient who he or she is and what he or she is trying to become. During
      this exploration, the nurse uses the senses, language, and a critical mind to do
      what no machine or test could-to see the underlying meaningfulness and internal
      coherence of the patient. The intuitive revelation would expose nursing
      interventions simultaneously. Moving beyond the myopic perspective of how to keep
      "person" central to the nursing metaparadigm, nursing is beginning to see the
      embodiment of the patient as a means for understanding and providing care for
      patients. The challenge that remains is for nurses to see their own embodiment
      and reflect on if or how it is at odds with the necessity of providing holistic
      care to patients. 

PMID- 24304633
TI  - L-theanine (suntheanin): effects of L-theanine, an amino acid derived from
      Camellia sinensis (green tea), on stress response parameters.

PMID- 24304634
TI  - Frequency of use and knowledge of the WHO-surgical checklist in Swiss hospitals:
      a cross-sectional online survey.
AB  - BACKGROUND: The WHO-surgical checklist is strongly recommended as a highly
      effective yet economically simple intervention to improve patient safety. Its use
      and potentially influential factors were investigated as little data exist on the
      current situation in Switzerland. METHODS: A cross-sectional online survey with
      members (N = 1378) of three Swiss professional associations of invasive health
      care professionals was conducted in German, French, and Italian. The survey
      assessed use of, knowledge of and satisfaction with the WHO-surgical checklist. T
      Tests and ANOVA were conducted to test for differences between professional
      groups. Bivariate correlations were computed to test for associations between
      measures of knowledge and satisfaction. RESULTS: 1090 (79.1%) reported the use of
      a surgical checklist. 346 (25.1%) use the WHO-checklist, 532 (38.6%) use the
      Swiss Patient Safety Foundation recommendations to avoid Wrong Site Surgery, and
      212 (15.7%) reported the use of other checklists. Satisfaction with checklist use
      was generally high (doctors: 71.9% satisfied, nurses: 60.8% satisfied) and
      knowledge was moderate depending on the use of the WHO-checklist. No association
      between measures of subjective and objective knowledge was found. CONCLUSIONS:
      Implementation of a surgical checklist remains an important task for health care
      institutions in Switzerland. Although checklist use is present in Switzerland on
      a regular basis, a substantial group of health care personnel still do not use a
      checklist as a routine. Influential factors and the associations among themselves
      need to be addressed in future studies in more detail.

PMID- 24304635
TI  - Identification of the phosphoglycerate dehydrogenase isoform EDA9 as the
      essential gene for embryo and male gametophyte development in Arabidopsis.
AB  - Three different pathways of serine (Ser) biosynthesis have been described in
      plants: the Glycolate pathway, which is part of the Photorespiratory pathway, and
      2 non-Photorespiratory pathways, the Glycerate and the Phosphorylated pathways.
      The Phosphorylated Pathway of Ser Biosynthesis (PPSB) has been known to exist
      since the 1950s, but its biological relevance was not revealed until quite
      recently when the last enzyme of the pathway, the Phosphoserine Phosphatase, was
      functionally characterized. In the associated study (1), we characterized a
      family of genes coding for putatite phosphoglycerate dehydrogenases (PGDH, 3
      PGDH, and EDA9), the first enzyme of the PPSB. A metabolomics study using
      overexpressing plants indicated that all PGDH family genes were able to regulate
      Ser homeostasis but only lacking of EDA9 expression caused drastic developmental
      defects. We provided genetic and molecular evidence for the essential role of
      EDA9 for embryo and pollen development. Here, some new insights into the
      physiological/molecular function of PPSB and Ser are presented and discussed. 

PMID- 24304636
TI  - Intraocular pressure reduction after cataract extraction in normal eyes:
      influence of ethnicity and anterior segment parameters - comment.

PMID- 24304637
TI  - Genome-wide identification and expression analyses of cytochrome P450 genes in
      mulberry (Morus notabilis).
AB  - Cytochrome P450s play critical roles in the biosynthesis of physiologically
      important compounds in plants. These compounds often act as defense toxins to
      prevent herbivory. In the present study, a total of 174 P450 genes of mulberry
      (Morus notabilis C.K.Schn) were identified based on bioinformatics analyses.
      These mulberry P450 genes were divided into nine clans and 47 families and were
      found to be expressed in a tissue-preferential manner. These genes were compared
      to the P450 genes in Arabidopsis thaliana. Families CYP80, CYP92, CYP728, CYP733,
      CYP736, and CYP749 were found to exist in mulberry, and they may play important
      roles in the biosynthesis of mulberry secondary metabolites. Analyses of the
      functional and metabolic pathways of these genes indicated that mulberry P450
      genes may participate in the metabolism of lipids, other secondary metabolites,
      xenobiotics, amino acids, cofactors, vitamins, terpenoids, and polyketides. These
      results provide a foundation for understanding of the structures and biological
      functions of mulberry P450 genes. 

PMID- 24304638
TI  - Comparison of expected treatment outcomes, obtained using risk models and
      international guidelines, with observed treatment outcomes in a Dutch cohort of
      patients with non-muscle-invasive bladder cancer treated with intravesical
      chemotherapy.
AB  - OBJECTIVE: To compare the risks according to the American Urological Association
      (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC)
      and Club Urologico Espanol de Tratamiento Oncologico (CUETO) classifications with
      real outcomes in a cohort of patients in the Netherlands, and to confirm that
      patients who were undertreated according to these risk models have worse outcomes
      than adequately treated patients. PATIENTS AND METHODS: Patients treated with
      complete transurethral resection of bladder tumour and intravesical chemotherapy
      were included. Not all patients would have received intravesical chemotherapy had
      they been treated to current standards, and thus comparison of the observed
      outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables
      and CUETO scoring model was possible. The cohort was reclassified according to
      the definitions of five index patients (IPs), as defined by the AUA guidelines,
      and three risk groups, defined according to the EAU guidelines, to compare the
      outcomes of undertreated patients with those of adequately treated patients.
      RESULTS: A total of 1001 patients were available for comparison with the AUA
      definitions and 728 patients were available for comparison with the EORTC and
      CUETO models. There was a large overlap between the observed outcomes and
      expected recurrence and progression probabilities when comparison was made using
      the EORTC risk tables. The observed recurrence outcomes were in general higher
      than the expected probabilities according to the CUETO risk classification,
      especially in the long term. No differences in progression were found when
      comparing these two models to the Dutch cohort. Patients who were undertreated
      according to the guidelines showed, in general, a higher risk of developing
      recurrence and progression. Limitations are i.a. its retrospective nature and the
      differences in grading system. CONCLUSION: Comparisons between the observed
      outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO
      risk models and the EORTC and AUA guidelines showed that lack of adherence to
      existing guidelines translates into worse outcomes.

PMID- 24304639
TI  - Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619
      induced contraction in rat aorta.
AB  - Inhibitory effects of docosahexaenoic acid (DHA) on blood vessel contractions
      induced by various constrictor stimulants were investigated in the rat thoracic
      aorta. The inhibitory effects of DHA were also compared with those of
      eicosapentaenoic acid (EPA) and linoleic acid (LA). DHA exhibited a strong
      inhibitory effect on the sustained contractions induced by U46619, a TXA(2)
      mimetic. This inhibitory effect of DHA was not affected by removal of the
      endothelium or by treatment with either indomethacin or N(omega)-nitro-l
      arginine. DHA also significantly diminished PGF(2alpha)-induced contraction but
      did not show any appreciable inhibitory effects on the contractions to both
      phenylephrine (PE) and high-KCl. Similarly, EPA exhibited significant inhibitory
      effects against the contractions induced by both U46619 and PGF(2alpha) without
      substantially affecting either PE- or high-KCl-induced contractions. However,
      both DHA and EPA generated more potent inhibitions against contractions induced
      by U46619 than those by PGF(2alpha). In contrast, LA did not show significant
      inhibitory effects against any contractions, including those induced by U46619.
      The present findings suggest that DHA and EPA elicit more selective inhibition
      against blood vessel contractions that are mediated through stimulation of
      prostanoid receptors than those through alpha-adrenoceptor stimulation or
      membrane depolarization. Although DHA and EPA have similar inhibitory potencies
      against prostanoid receptor-mediated contractions, they had a more potent
      inhibition against TXA(2) receptor (TP receptor)-mediated contractions than
      against PGF(2alpha) receptor (FP receptor)-mediated responses. Selective
      inhibition by either DHA or EPA of prostanoid receptor-mediated blood vessel
      contractions may partly underlie the mechanisms by which these omega-3
      polyunsaturated fatty acids exert their circulatory-protective effects.

PMID- 24304640
TI  - Design and test of a biosensor-based multisensorial system: a proof of concept
      study.
AB  - Sensors are often organized in multidimensional systems or networks for
      particular applications. This is facilitated by the large improvements in the
      miniaturization process, power consumption reduction and data analysis techniques
      nowadays possible. Such sensors are frequently organized in multidimensional
      arrays oriented to the realization of artificial sensorial systems mimicking the
      mechanisms of human senses. Instruments that make use of these sensors are
      frequently employed in the fields of medicine and food science. Among them, the
      so-called electronic nose and tongue are becoming more and more popular. In this
      paper an innovative multisensorial system based on sensing materials of
      biological origin is illustrated. Anthocyanins are exploited here as chemical
      interactive materials for both quartz microbalance (QMB) transducers used as gas
      sensors and for electrodes used as liquid electrochemical sensors. The optical
      properties of anthocyanins are well established and widely used, but they have
      never been exploited as sensing materials for both gas and liquid sensors in non
      optical applications. By using the same set of selected anthocyanins an
      integrated system has been realized, which includes a gas sensor array based on
      QMB and a sensor array for liquids made up of suitable Ion Sensitive Electrodes
      (ISEs). The arrays are also monitored from an optical point of view. This
      embedded system, is intended to mimic the working principles of the nose, tongue
      and eyes. We call this setup BIONOTE (for BIOsensor-based multisensorial system
      for mimicking NOse, Tongue and Eyes). The complete design, fabrication and
      calibration processes of the BIONOTE system are described herein, and a number of
      preliminary results are discussed. These results are relative to: (a) the
      characterization of the optical properties of the tested materials; (b) the
      performance of the whole system as gas sensor array with respect to ethanol,
      hexane and isopropyl alcohol detection (concentration range 0.1-7 ppm) and as a
      liquid sensor array (concentration range 73-98 MUM). 

PMID- 24304643
TI  - Fabrication of a microneedle/CNT hierarchical micro/nano surface electrochemical
      sensor and its in-vitro glucose sensing characterization.
AB  - We report fabrication of a microneedle-based three-electrode integrated
      electrochemical sensor and in-vitro characterization of this sensor for glucose
      sensing applications. A piece of silicon was sequentially dry and wet etched to
      form a 15 * 15 array of tall (approximately 380 um) sharp silicon microneedles.
      Iron catalyst was deposited through a SU-8 shadow mask to form the working
      electrode and counter electrode. A multi-walled carbon nanotube forest was grown
      directly on the silicon microneedle array and platinum nano-particles were
      electrodeposited. Silver was deposited on the Si microneedle array through
      another shadow mask and chlorinated to form a Ag/AgCl reference electrode. The 3
      electrode electrochemical sensor was tested for various glucose concentrations in
      the range of 3~20 mM in 0.01 M phosphate buffered saline (PBS) solution. The
      sensor's amperometric response to the glucose concentration is linear and its
      sensitivity was found to be 17.73 +/- 3 MUA/mM-cm2. This microneedle-based sensor
      has a potential to be used for painless diabetes testing applications. 

PMID- 24304646
TI  - Strategies in intervention programmes for obese youth: implication of the age and
      the type of physical activities.
AB  - The aim of this study was to assess the effects of age and type of physical
      activity on anthropometric measures of obese youth participating in an
      intervention programme. Subjects included 37 obese children (12.5 +/- 2.9 years).
      The programme consisted of a unique programme of physical activity and health
      education. Assessments included body mass index (BMI), body composition and
      ability to perform sport activities. Paired t-tests were used to assess the
      effects of intervention, and chi square was used to assess interaction between
      measures. Findings suggest significant decrease in Z-scores of BMI and an
      improvement in the ability to perform sport activities (P<0.05). The
      effectiveness of the programme has more impact on children than adolescents
      (P<0.05). Improvements were greater in team versus net sports (P<0.05). Results
      show that intervention strategies have to be different according to the age to
      have a favourable effect on anthropometric characteristic and the consequences of
      obesity childhood and adulthood. The findings suggest that the intervention
      programme was of greater benefit for children than adolescents. 

PMID- 24304644
TI  - Midgut transcriptome profiling of Anoplophora glabripennis, a lignocellulose
      degrading cerambycid beetle.
AB  - BACKGROUND: Wood-feeding insects often work in collaboration with microbial
      symbionts to degrade lignin biopolymers and release glucose and other fermentable
      sugars from recalcitrant plant cell wall carbohydrates, including cellulose and
      hemicellulose. Here, we present the midgut transcriptome of larval Anoplophora
      glabripennis, a wood-boring beetle with documented lignin-, cellulose-, and
      hemicellulose- degrading capabilities, which provides valuable insights into how
      this insect overcomes challenges associated with feeding in woody tissue.
      RESULTS: Transcripts from putative protein coding regions of over 9,000 insect
      derived genes were identified in the A. glabripennis midgut transcriptome using a
      combination of 454 shotgun and Illumina paired-end reads. The most highly
      expressed genes predicted to encode digestive-related enzymes were trypsins,
      carboxylesterases, beta-glucosidases, and cytochrome P450s. Furthermore, 180
      unigenes predicted to encode glycoside hydrolases (GHs) were identified and
      included several GH 5, 45, and 48 cellulases, GH 1 xylanases, and GH 1 beta
      glucosidases. In addition, transcripts predicted to encode enzymes involved in
      detoxification were detected, including a substantial number of unigenes
      classified as cytochrome P450s (CYP6B) and carboxylesterases, which are
      hypothesized to play pivotal roles in detoxifying host tree defensive chemicals
      and could make important contributions to A. glabripennis' expansive host range.
      While a large diversity of insect-derived transcripts predicted to encode
      digestive and detoxification enzymes were detected, few transcripts predicted to
      encode enzymes required for lignin degradation or synthesis of essential
      nutrients were identified, suggesting that collaboration with microbial enzymes
      may be required for survival in woody tissue. CONCLUSIONS: A. glabripennis
      produces a number of enzymes with putative roles in cell wall digestion,
      detoxification, and nutrient extraction, which likely contribute to its ability
      to thrive in a broad range of host trees. This system is quite different from the
      previously characterized termite fermentation system and provides new
      opportunities to discover enzymes that could be exploited for cellulosic ethanol
      biofuel production or the development of novel methods to control wood-boring
      pests.

PMID- 24304645
TI  - Designing of interferon-gamma inducing MHC class-II binders.
AB  - BACKGROUND: The generation of interferon-gamma (IFN-gamma) by MHC class II
      activated CD4+ T helper cells play a substantial contribution in the control of
      infections such as caused by Mycobacterium tuberculosis. In the past, numerous
      methods have been developed for predicting MHC class II binders that can activate
      T-helper cells. Best of author's knowledge, no method has been developed so far
      that can predict the type of cytokine will be secreted by these MHC Class II
      binders or T-helper epitopes. In this study, an attempt has been made to predict
      the IFN-gamma inducing peptides. The main dataset used in this study contains
      3705 IFN-gamma inducing and 6728 non-IFN-gamma inducing MHC class II binders.
      Another dataset called IFNgOnly contains 4483 IFN-gamma inducing epitopes and
      2160 epitopes that induce other cytokine except IFN-gamma. In addition we have
      alternate dataset that contains IFN-gamma inducing and equal number of random
      peptides. RESULTS: It was observed that the peptide length, positional
      conservation of residues and amino acid composition affects IFN-gamma inducing
      capabilities of these peptides. We identified the motifs in IFN-gamma inducing
      binders/peptides using MERCI software. Our analysis indicates that IFN-gamma
      inducing and non-inducing peptides can be discriminated using above features. We
      developed models for predicting IFN-gamma inducing peptides using various
      approaches like machine learning technique, motifs-based search, and hybrid
      approach. Our best model based on the hybrid approach achieved maximum prediction
      accuracy of 82.10% with MCC of 0.62 on main dataset. We also developed hybrid
      model on IFNgOnly dataset and achieved maximum accuracy of 81.39% with 0.57 MCC.
      CONCLUSION: Based on this study, we have developed a webserver for predicting i)
      IFN-gamma inducing peptides, ii) virtual screening of peptide libraries and iii)
      identification of IFN-gamma inducing regions in antigen
      (http://crdd.osdd.net/raghava/ifnepitope/).

PMID- 24304647
TI  - Effects of ensiling processes and antioxidants on fatty acid concentrations and
      compositions in corn silages.
AB  - BACKGROUND: Corn silage is the main dietary component used for ruminant breeding
      in China and is an important dietary source of fatty acids for these animals.
      However, little is known regarding effective means to protect the fatty acid (FA)
      contents in silages. In this study, we examined the changes in FA contents and
      compositions during corn ensiling and screened several antioxidants for their
      inhibition of lipid oxidation during corn ensiling. METHODS: We conducted two
      different experiments. In Experiment 1, corn was ensiled in 30 polyethylene
      bottles (bottle volume: 1 L, silage density: 600 g/dm3) and three bottles were
      opened at 0.5 d, 1 d, 1.5 d, 2 d, 2.5 d, 3 d, 5 d, 7 d, 14 d, and 28 d after
      ensiling. In Experiment 2, corn was treated with various antioxidants: (1) No
      additives (CK); (2) BHA (Butylated hydroxyanisole); (3) TBHQ (Tertiary butyl
      hydroquinone); (4) TPP (Tea polyphenols); and (5) VE (Vitamin E). These
      treatments were applied at 50 mg/kg and 100 mg/kg of fresh weight with each
      treatment replicated 3 times. RESULTS: During ensiling in Experiment 1, saturated
      fatty acids (SFA; C16:0 and C18:0) and malondialdehyde (MDA) contents tended to
      increase, whereas unsaturated fatty acids (UFA; C18:1, C18:2 and C18:3) tended to
      decrease. However, these changes were only significant on the first 2 days of
      ensiling. In Experiment 2, all of the antioxidants tested affected the total FA
      contents and those of unsaturated fatty acids (C18:1, C18:2 and C18:3) and MDA.
      The effects of TBHQ and TPP were greater than those of the other antioxidants.
      CONCLUSIONS: The reduced total FA contents in corn silages were due to
      unsaturated fatty acids' oxidation during the early stages of ensiling. Adding an
      antioxidant could prevent fatty acids' oxidation in corn silages.

PMID- 24304648
TI  - Circulating microRNA expressions in colorectal cancer as predictors of response
      to chemotherapy.
AB  - Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the
      third leading cause of cancer death in the Western world. Chemotherapy has been
      shown to improve outcomes in patients with CRC; however, only selected patients
      would benefit from this treatment. We aimed to identify predictors of response to
      chemotherapy in CRC using circulating microRNAs (miRNAs). We studied differential
      miRNA expression by miRNA array from serum of 253 patients who had chemotherapy
      treatment. We screened the differentially expressed serum miRNAs with TaqMan low
      density arrays using pooled CRC patient serum samples. Differential expression
      was validated using hydrolysis probe-based stem-loop quantitative reverse
      transcription PCR in individual samples. We performed additional unsupervised
      cluster to analyse the differential expression of serum miRNA between the
      chemosensitive and chemoresistant patients. A distinct miRNA expression signature
      in response to chemotherapy was identified. The TaqMan low-density array results
      demonstrated that 17 serum miRNAs could predict chemosensitivity and
      chemoresistance. The quantitative reverse transcription PCR analysis further
      identified a profile of five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and
      miR-372) as a biomarker for predicting the chemosensitivity of CRC. The areas
      under the receiver operating characteristic curve of this five-serum miRNA
      signature were 0.841 and 0.918 for the two sets of serum samples, respectively.
      We identified a group of miRNA predictors in response to chemosensitivity for CRC
      patients. This could lead to a significant improvement in chemotherapy regimen
      selection strategy and personalized CRC management. 

PMID- 24304649
TI  - The selection of suitable columns for a reversed-phase liquid chromatographic
      separation of beta-lactam antibiotics and related substances via chromatographic
      column parameters.
AB  - The selection of RP-LC columns suitable for a particular analysis in official
      compendia is difficult as only a general description of the stationary phase in
      the description of a LC method is given. General methods to characterize RP-LC
      columns often assume that each of the column parameters is equally important.
      This can cause the user to select columns inappropriate for particular analyses.
      This paper focuses on the relationship between the critical peak pairs and the
      column parameters (H, S, A, B, and C) in the Snyder/Dolan column characterization
      methodology to find the key parameters influencing real separations. Some
      varieties of beta-lactam antibiotics and their related compounds were used as
      test compounds. We found column parameter A to be the most important factor
      affecting their separation. Parameters B and C also played an important role in
      some separation processes. This indicated that the hydrogen bonding of column and
      solute can directly affect the separation of beta-lactam antibiotics. Choosing
      columns for which column parameter A is near 0.1 can facilitate the ideal
      separations of impurities from beta-lactam antibiotics. The most suitable column
      for any common pharmaceutical analysis could be selected easily if the key column
      parameters would be given in the description of the chromatographic method. For
      these reasons, key column parameters should be listed in the monographs of
      official compendia. 

PMID- 24304650
TI  - Determination of void volume in normal phase liquid chromatography.
AB  - Void volume is an important fundamental parameter in chromatography. Little prior
      discussion has focused on the determination of void volume in normal phase liquid
      chromatography (NPLC). Various methods to estimate the total void volume are
      compared: pycnometry; minor disturbance method based on injection of weak
      solvent; tracer pulse method; hold-up volume based on unretained compounds; and
      accessible volume based on Martin's rule and its descendants. These are applied
      to NPLC on silica, RingSep and DNAP columns. Pycnometry provides a theoretically
      maximum value for the total void volume and should be performed at least once for
      each new column. However, pycnometry does not reflect the volume of adsorbed
      strong solvent on the stationary phase, and so only yields an accurate void
      volume for weaker mobile phase conditions. 1,3,5-Tri-t-butyl benzene (TTBB)
      results in hold-up volumes that are convenient measures of the void volume for
      all eluent conditions on charge-transfer columns (RingSep and DNAP), but is
      weakly retained under weak eluent conditions on silica. Injection of the weak
      mobile phase component (hexane) may be used to determine void volume, but care
      must be exercised to select the appropriate disturbance feature. Accessible
      volumes, that are determined using a homologous series, are always biased low,
      and are not recommended as a measure of the void volume. 

PMID- 24304651
TI  - Molecular orientation of gel forming compounds and their effect on molecular
      shape selectivity in liquid chromatography.
AB  - Double-alkylated glutamic acid and aminoadipic acid derived gel systems (G1 and
      G2) have been prepared and then grafted onto silica particles. Gel-forming
      compounds-grafted silica particles (Sil-G1 and Sil-G2) were then applied for the
      liquid chromatographic separation of shape-constrained isomers of polycyclic
      aromatic hydrocarbons (PAHs) and tocopherols as stationary phases. G1 and G2 were
      analyzed before and after immobilization onto silica. Elemental analysis and
      thermogravimentric analysis (TGA) results showed almost the same amounts of
      organic phases were grafted in Sil-G1 and Sil-G2 phases. However, chromatographic
      results showed large differences of molecular-shape selectivity between the
      stationary phases. Little change in the chemical structures of the gel-forming
      compounds can change the molecular orientation as well as drastic change in
      molecular recognition in liquid chromatography. Molecular orientation of the
      functional groups affected the interaction mechanism for the separation of shape
      constrained isomers. Comparison of the shape selectivity of Sil-G1 and Sil-G2
      phases with other commercial columns is also described. 

PMID- 24304652
TI  - Introgression and phenotypic assimilation in Zimmerius flycatchers (Tyrannidae):
      population genetic and phylogenetic inferences from genome-wide SNPs.
AB  - Genetic introgression is pervasive in nature and may lead to large-scale
      phenotypic assimilation and/or admixture of populations, but there is limited
      knowledge on whether large phenotypic changes are typically accompanied by high
      levels of introgression throughout the genome. Using bioacoustic, biometric, and
      spectrophotometric data from a flycatcher (Tyrannidae) system in the Neotropical
      genus Zimmerius, we document a mosaic pattern of phenotypic admixture in which a
      population of Zimmerius viridiflavus in northern Peru (henceforth "mosaic") is
      vocally and biometrically similar to conspecifics to the south but shares plumage
      characteristics with a different species (Zimmerius chrysops) to the north. To
      clarify the origins of the mosaic population, we used the RAD-seq approach to
      generate a data set of 37,361 genome-wide single nucleotide polymorphisms (SNPs).
      A range of population-genetic diagnostics shows that the genome of the mosaic
      population is largely indistinguishable from southern Z. viridiflavus and
      distinct from northern Z. chrysops, and the application of parsimony and species
      tree methods to the genome-wide SNP data set confirms the close affinity of the
      mosaic population with southern Z. viridiflavus. Even so, using a subset of 2710
      SNPs found across all sampled lineages in configurations appropriate for a
      recently proposed statistical ("ABBA/BABA") test that distinguishes gene flow
      from incomplete lineage sorting, we detected low levels of gene flow from
      northern Z. chrysops into the mosaic population. Mapping the candidate loci for
      introgression from Z. chrysops into the mosaic population to the zebra finch
      genome reveals close linkage with genes significantly enriched in functions
      involving cell projection and plasma membranes. Introgression of key alleles may
      have led to phenotypic assimilation in the plumage of mosaic birds, suggesting
      that selection may have been a key factor facilitating introgression. 

PMID- 24304653
TI  - Noninvasive generation of aortic pressure from radial pressure waveform by
      applanation tonometry, brachial cuff calibration, and generalized transfer
      function.

PMID- 24304654
TI  - Assessment of central blood pressure in patients with type 2 diabetes: a
      comparison between SphygmoCor and invasively measured values.
AB  - BACKGROUND: The SphygmoCor is used for noninvasive assessment of ascending aortic
      blood pressure (BP). However, the validity of the SphygmoCor transfer function
      has not been tested in an exclusively type 2 diabetic patient sample. Calibration
      with systolic (SBP) and diastolic (DBP) brachial BP has previously been
      associated with substantial imprecision of central BP estimates. We hypothesized
      that different noninvasive calibration strategies might improve the accuracy of
      the estimated ascending aortic BPs. METHODS: In 34 patients with type 2 diabetes
      we estimated ascending aortic SBP and DBP using the SphygmoCor device and
      compared these data with invasively recorded data. The validity of the transfer
      function was assessed by calibrating with invasively recorded DBP and mean BP
      (MBP). The influence of noninvasive calibration strategies was assessed by
      calibrating with brachial oscillometric SBP+DBP vs. DBP+MBP using a form factor
      (ff) of 0.33 and 0.40, respectively. RESULTS: When calibrating with invasive BP,
      the difference between estimated and invasively measured ascending aortic SBP and
      DBP was -2.3+/-5.6/1.0+/-0.9 mm Hg. When calibrating with oscillometric brachial
      BPs, the differences were -9.6+/-8.1/14.1+/-6.2 mm Hg (calibration with SBP and
      DBP), -8.3+/-11.7/13.9+/-6.1 mm Hg (DBP and MBP; ff = 0.33), and 1.9+/
      12.2/14.1+/-6.2 mm Hg (DBP and MBP; ff = 0.40), respectively. Calibration with
      the average of 3 brachial BPs did not improve accuracy. CONCLUSIONS: The
      SphygmoCor transfer function seems valid in patients with type 2 diabetes.
      Noninvasive calibration with DBP and MBP (ff = 0.40) enables accurate estimation
      of mean ascending aortic SBP at the group level. However, the wide limits of
      agreement indicate limited accuracy in the individual patient. CLINICAL TRIALS
      REGISTRATION: Clinical Trials No. NCT01538290.

PMID- 24304655
TI  - Transgenic overexpression of uncoupling protein 2 attenuates salt-induced
      vascular dysfunction by inhibition of oxidative stress.
AB  - BACKGROUND: Ablation of uncoupling protein 2 (UCP2) has been involved in the
      enhancement of salt sensitivity associated with increased superoxide level and
      decreased nitric oxide (NO) bioavailability. However, the role of overexpression
      of UCP2 in salt-induced vascular dysfunction remains elusive. METHODS: UCP2
      transgenic (TG) and wild-type (WT) mice were placed on either a normal-salt (NS,
      0.5%) or a high-salt (HS, 8%) diet for 12 weeks. Blood pressure (BP) and
      hypotensive responses were measured, and the vascular tone, superoxide level, and
      NO bioavailability in aortas were measured in each group. RESULTS: The TG mice
      had increased expression and function of UCP2 in vascular smooth muscle cells.
      The acetylcholine (ACh)- and nitroglycerin (NTG)-induced hypotensive responses
      and aortic relaxations were significantly blunted in WT mice fed with an HS diet
      compared with an NS diet. These harmful effects were prevented in UCP2 TG mice.
      The impairments of ACh- and NTG-induced relaxation in aorta were inhibited by the
      endothelial NO synthase (eNOS) inhibitor L-NAME and mitochondrial antioxidant
      MitoQ, respectively. The HS intake led to a significant increase in superoxide
      production and a comparable decrease in NO bioavailability in aortas, and these
      effects were blunted in UCP2 TG mice. The expression of UCP2 was slightly
      increased in the HS group. However, the expression and phosphorylation of eNOS
      were not affected by an HS diet and overexpression of UCP2. CONCLUSIONS: These
      findings suggest that overexpression of UCP2 can ameliorate salt-induced vascular
      dysfunction. This beneficial effect of UCP2 is mediated by decreased superoxide
      and reserved NO bioavailability.

PMID- 24304656
TI  - Aliskiren/amlodipine vs. aliskiren/hydrochlorothiazide in hypertension: indirect
      meta-analysis of trials comparing the two combinations vs. monotherapy.
AB  - BACKGROUND: Aliskiren, a direct renin inhibitor, is effective for reducing blood
      pressure (BP) in patients with hypertension when combined with amlodipine or
      hydrochlorothiazide (HCTZ). However, the efficacy and tolerability of the 2
      combinations are unclear. We performed a meta-analysis of randomized controlled
      trials of aliskiren/amlodpine and aliskiren/HCTZ for hypertension. METHODS: The
      Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and the Novartis
      clinical trial database were searched through December 2012 for reports of
      randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ vs.
      monotherapy in patients with hypertension. The main outcome measures were
      reduction in systolic BP and diastolic BP from baseline and rates of therapeutic
      response and BP control. Tolerance of aliskiren/amlodipine and aliskiren/HCTZ was
      also analyzed. Outcomes were initially pooled by standard random-effects methods,
      producing a weighted mean difference (WMD) or risk ratio (RR) and 95% confidence
      intervals (CIs). The pooled estimates were then used for adjusted indirect
      comparisons. RESULTS: We selected 19 reports of trials involving 13,614
      participants. Aliskiren/amlodpine and aliskiren/HCTZ were more effective than
      monotherapy in controlling BP. Aliskiren/amlodipine was significantly more
      effective than aliskiren/HCTZ in reducing systolic BP (WMD = -3.36 mm Hg; 95% CI
      = -4.64 to 2.07 mm Hg) and diastolic BP (WMD = -3.49 mm Hg; 95% CI = -4.34 to
      2.63 mm Hg). As compared with aliskiren/HCTZ, alikiren/amlodipine was associated
      with higher rate of therapeutic response (RR = 1.23; 95% CI = 1.14-1.33) and BP
      control (RR = 1.24; 95% CI = 1.11-1.39). Number of adverse events and withdrawals
      due to adverse events were similar with aliskiren/amlodipine and aliskiren/HCTZ.
      CONCLUSIONS: BP control is better with aliskiren combined with amlodipine or HCTZ
      than with monotherapy, with aliskiren/amlodipine being more effective than
      aliskiren/HCTZ.

PMID- 24304657
TI  - Central hemodynamics could explain the inverse association between height and
      cardiovascular mortality.
AB  - BACKGROUND: Mechanisms underlying the inverse relationship between height and
      cardiovascular mortality are unknown but could relate to central hemodynamics. We
      sought to determine the relation of height to central and peripheral
      hemodynamics, as well as clinical characteristics. METHODS: The study population
      was comprised of 1,152 randomly selected community-dwelling adults (aged 67.7 +/-
      12.3 years; 48% men). Brachial blood pressure (BP) was recorded by
      sphygmomanometry; central BP and aortic pulse wave velocity were estimated by
      applanation tonometry. Stepwise multiple regression analysis was used to
      determine associations between height and central and peripheral hemodynamics.
      RESULTS: Height was not significantly associated with aortic pulse wave velocity
      in men or women. The relationship with height and brachial systolic BP was
      borderline in women (beta = -0.115; P = 0.051) but not significant in men (beta =
      -0.096; P = 0.09). Conversely, central systolic BP, estimated by transfer
      function (beta = -0.139 for men [betaM]; beta = -0.172 for women [betaW]) or
      radial second systolic peak (beta M = -0.239; beta W = -0.281), augmentation
      index at 75 bpm (beta M = -0.189; beta W = -0.224), and aortic pulse wave timing
      (beta M = 0.224; beta W = 0.262) were independently associated with height in
      both sexes (P < 0.003 for all). Both men and women of greater than median height
      were less likely to have coronary artery disease (P < 0.05), to have systemic
      hypertension (P < 0.01), or to be taking vasoactive medication (P < 0.001)
      compared with participants of less than median height. CONCLUSIONS: Even after
      correcting for conventional cardiovascular risk factors, taller individuals have
      more favorable central hemodynamics and reduced evidence of coronary artery
      disease compared with shorter individuals. These findings may help explain the
      decreased cardiovascular risk associated with being taller and also have
      important clinical consequences regarding therapy.

PMID- 24304658
TI  - From research to practice: how OPUS treatment was accepted and implemented
      throughout Denmark.
AB  - BACKGROUND: The early phases of psychosis have been hypothesized to constitute a
      critical period, a window of opportunity. At the same time, the early phases of
      psychosis are associated with increased risk of unwanted outcome, such as
      suicidal behaviour and social isolation. This was the background for the
      emergence of early intervention services, and in Denmark, the OPUS trial was
      initiated as part of that process. METHODS: Modified assertive community
      treatment, together with family involvement and social skills training,
      constituted the core elements in the original programme. A total of 547 patients
      with first-episode psychosis were included in the trial. RESULTS: To summarize
      briefly the results of the OPUS trial: the OPUS treatment was superior to
      standard treatment in reducing psychotic and negative symptoms and substance
      abuse, in increasing user satisfaction and adherence to treatment, and in
      reducing use of bed days and days in supported housing. Moreover, relatives
      included in the OPUS treatment were less strained and had a higher level of
      knowledge about schizophrenia and higher user satisfaction. DISCUSSION: The OPUS
      treatment was implemented throughout Denmark. Training courses were developed and
      manuals and books were published. Regional health authorities had access to
      national grants for implementing early intervention services; as a result, OPUS
      teams were disseminated throughout the country. The content of the treatment is
      now further developed, and new elements are being tried out - such as individual
      placement and support, lifestyle changes, cognitive remediation, specialized
      treatment for substance abuse and different kinds of user involvement.

PMID- 24304659
TI  - Improvement of in-hospital telemetry monitoring in coronary care units: an
      intervention study for achieving optimal electrode placement and attachment,
      hygiene and delivery of critical information to patients.
AB  - BACKGROUND: In-hospital telemetry monitoring is important for diagnosis and
      treatment of patients at risk of developing life-threatening arrhythmias. It is
      widely used in critical and non-critical care wards. Nurses are responsible for
      correct electrode placement, thus ensuring optimal quality of the monitoring. The
      aims of this study were to determine whether a complex educational intervention
      improves (a) optimal electrode placement, (b) hygiene, and (c) delivery of
      critical information to patients (reason for monitoring, limitations in cellular
      phone use, and not to leave the ward without informing a member of staff).
      METHODS: A prospective interventional study design was used, with data collection
      occurring over two six-week periods: before implementation of the intervention
      (n=201) and after the intervention (n=165). Standard abstraction forms were used
      to obtain data on patients' clinical characteristics, and 10 variables related to
      electrode placement and attachment, hygiene and delivery of critical information.
      RESULTS: At pre-intervention registration, 26% of the electrodes were misplaced.
      Twelve per cent of the patients received information about limiting their
      cellular phone use while monitored, 70% were informed of the purpose of
      monitoring, and 71% used a protective cover for their unit. Post-intervention,
      outcome measures for the three variables improved significantly: use of
      protective cover (p<0.001), information about the purpose of monitoring (p=0.005)
      and information about limitations in cellular phone use (p=0.003). Nonetheless,
      23% of the electrodes were still misplaced. CONCLUSION: The study highlights the
      need for better, continued education for in-hospital telemetry monitoring in
      coronary care units, and other units that monitor patients with telemetry.

PMID- 24304660
TI  - Comparative proteomic analysis of genetically modified maize grown under
      different agroecosystems conditions in Brazil.
AB  - BACKGROUND: Profiling technologies allow the simultaneous measurement and
      comparison of thousands of cell components without prior knowledge of their
      identity. In the present study, we used two-dimensional gel electrophoresis
      combined with mass spectrometry to evaluate protein expression of Brazilian
      genetically modified maize hybrid grown under different agroecosystems
      conditions. To this effect, leaf samples were subjected to comparative analysis
      using the near-isogenic non-GM hybrid as the comparator. RESULTS: In the first
      stage of the analysis, the main sources of variation in the dataset were
      identified by using Principal Components Analysis which correlated most of the
      variation to the different agroecosystems conditions. Comparative analysis within
      each field revealed a total of thirty two differentially expressed proteins
      between GM and non-GM samples that were identified and their molecular functions
      were mainly assigned to carbohydrate and energy metabolism, genetic information
      processing and stress response. CONCLUSIONS: To the best of our knowledge this
      study represents the first evidence of protein identities with differentially
      expressed isoforms in Brazilian MON810 genetic background hybrid grown under
      field conditions. As global databases on outputs from "omics" analysis become
      available, these could provide a highly desirable benchmark for safety
      assessments.

PMID- 24304661
TI  - TET3-OGT interaction increases the stability and the presence of OGT in
      chromatin.
AB  - Gene expression is controlled by alterations in the epigenome, including DNA
      methylation and histone modification. Recently, it was reported that 5
      methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by proteins
      in the ten-eleven translocation (TET) family. This conversion is believed to be
      part of the mechanism by which methylated DNA is demethylated. Moreover, histones
      undergo modifications such as phosphorylation and acetylation. In addition,
      modification with O-linked-N-acetylglucosamine (O-GlcNAc) by O-GlcNAc transferase
      (OGT) was recently identified as a novel histone modification. Herein, we focused
      on TET3, the regulation of which is still unclear. We attempted to elucidate the
      mechanism of its regulation by biochemical approaches. First, we conducted mass
      spectrometric analysis in combination with affinity purification of FLAG-TET3,
      which identified OGT as an important partner of TET3. Co-immunoprecipitation
      assays using a series of deletion mutants showed that the C-terminal H domain of
      TET3 was required for its interaction with OGT. Furthermore, we showed that TET3
      is GlcNAcylated by OGT, although the GlcNAcylation did not affect the global
      hydroxylation of methylcytosine by TET3. Moreover, we showed that TET3 enhanced
      its localization to chromatin through the stabilization of OGT protein. Taken
      together, we showed a novel function of TET3 that likely supports the function of
      OGT. 

PMID- 24304662
TI  - Treating fatty liver and insulin resistance.

PMID- 24304663
TI  - The effect of psychosocial stress on single mothers' smoking.
AB  - BACKGROUND: Evidence suggests an increased risk of smoking among single mothers
      as compared to their cohabitating counterparts. This article examines the role of
      psychosocial stress in mediating the relationship between single motherhood and
      smoking. METHODS: Data were derived from a cross-sectional population based
      sample of German women (n = 3129) with underage children (0-18 years of age).
      Perceived stress was measured with 13 items covering socioeconomic as well as
      family- and parenting-related stressors. According to Baron and Kenny (1986) a
      series of logistic regression models was applied to investigate the role of
      psychosocial stress as a mediator on the relationship between single motherhood
      and smoking. RESULTS: About 44.0% of single mothers smoked daily, whereas only
      26.2% of cohabitating mothers did. Single mothers reported more stress related to
      their economic situation, occupation and family than partnered mothers. Out of
      the original 13 stressors only 'conflicts with the partner or ex-partner' and
      'financial worries' remained significant in explaining single mothers' higher
      risk of smoking. Against expectation, stress due to household requirements and
      family demands was associated with lower odds of single mothers' smoking. After
      controlling for psychosocial stress, the odds ratio of single mothers' moderate
      smoking (< 20 cig./day) decreased slightly from 1.75 to 1.66 (explained fraction
      XF = 12.0%) and with respect to heavy smoking (>= 20 cig./day) more pronounced
      from 2.56 to 2.01 (XF = 35.3%). CONCLUSIONS: It can be stated that single
      mothers' heavy more than moderate smoking appeared to be mediated by perceived
      psychosocial stress. Out of all stressors considered, financial worries were of
      paramount significance in explaining single mothers' heavy smoking while some
      family-related stressors rather appeared to keep single mothers from smoking.
      Overall, a higher stress exposure explains partly but not sufficiently single
      mothers' increased smoking rates.

PMID- 24304665
TI  - Intraocular pressure reduction after cataract extraction in normal eyes:
      influence of ethnicity and anterior segment parameters - response.

PMID- 24304664
TI  - Association of cellular and molecular responses in the rat mammary gland to
      17beta-estradiol with susceptibility to mammary cancer.
AB  - BACKGROUND: We are using ACI and BN rats, which differ markedly in their
      susceptibility to 17beta-estradiol (E2)-induced mammary cancer, to identify
      genetic variants and environmental factors that determine mammary cancer
      susceptibility. The objective of this study was to characterize the cellular and
      molecular responses to E2 in the mammary glands of ACI and BN rats to identify
      qualitative and quantitative phenotypes that associate with and/or may confer
      differences in susceptibility to mammary cancer. METHODS: Female ACI and BN rats
      were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology
      were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell
      proliferation and epithelial density were evaluated by quantitative
      immunohistochemistry. Apoptosis was evaluated by quantitative western blotting
      and flow cytometry. Mammary gland differentiation was examined by
      immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and
      quantitative western blotting assays. Extracellular matrix (ECM) associated
      collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation
      (SHG) microscopy. RESULTS: The luminal epithelium of ACI rats exhibited a rapid
      and sustained proliferative response to E2. By contrast, the proliferative
      response exhibited by the mammary epithelium of BN rats was restrained and
      transitory. Moreover, the epithelium of BN rats appeared to undergo
      differentiation in response to E2, as evidenced by production of milk proteins as
      well as luminal ectasia and associated changes in the ECM. Marked differences in
      expression of genes that encode proteins with well-defined roles in mammary gland
      development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and
      milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7,
      Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed.
      CONCLUSIONS: We propose that these cellular and molecular phenotypes are
      heritable and may underlie, at least in part, the differences in mammary cancer
      susceptibility exhibited by ACI and BN rats.

PMID- 24304666
TI  - A systems biology approach for the identification of target genes for the
      improvement of itaconic acid production in Aspergillus species.
AB  - BACKGROUND: In this paper, a clone based transcriptome analysis towards the
      identification of genes related to itaconic acid production in Aspergillus
      terreus was carried out as an extension of a previously published a clone-based
      transcriptome analysis from a set of batch fermentation experiments. Also a
      publically available A. niger transcriptome dataset from cultures similar to
      those of the A. terreus data set was analyzed to evaluate the specificity of the
      approach followed for A. terreus. RESULTS: Besides the itaconic acid gene cluster
      (cis-aconitate decarboxylase, mitochondrial tri-carboxylic acid transporter and
      major facilitator superfamily transporter) discovered previously, additional
      genes of interest were identified in the A. terreus transcriptome data
      correlating to itaconic acid production, including 6 genes encoding enzymes in
      glycolysis and the pentose phosphate pathway, 4 genes functioning in vitamins
      synthesis, and a gene encoding a copper transporter. Only three of the 83 low pH
      specific genes identified from the A. niger dataset corresponded to high itaconic
      acid / low pH expressed genes identified from the A. terreus data set. However,
      in all three cases, the regulation of pH dependent gene expression was completely
      different between the two species. CONCLUSIONS: An extended clone based
      transcriptome analysis using a clone based transcription array to identify genes
      correlating with itaconic acid production revealed novel genes both in the
      central metabolism and in other more secondary pathways such as vitamin
      biosynthesis and Cu2+ transport, providing targets for further metabolic and
      process engineering to optimize itaconic acid production.

PMID- 24304667
TI  - Out of the woods. Ash dieback and the future of emergent pathogenomics.

PMID- 24304668
TI  - Evidence for the presence of lipid-free monomolecular apolipoprotein A-1 in
      plasma.
AB  - The first step in reverse cholesterol transport is a process by which lipid-free
      or lipid-poor apoA-1 removes cholesterol from cells through the action of ATP
      binding cassette transporter A1 at the plasma membrane. However the structure and
      composition of lipid-free or -poor apoA-1 in plasma remains obscure. We
      previously obtained a monoclonal antibody (MAb) that specifically recognizes apoA
      1 in prebeta1-HDL, the smallest apoA-1-containing particle in plasma, which we
      used to establish a prebeta1-HDL ELISA. Here, we purified prebeta1-HDL from fresh
      normal plasma using said antibody, and analyzed the composition and structure.
      ApoA-1 was detected, but neither phospholipid nor cholesterol were detected in
      the purified prebeta1-HDL. Only globular, not discoidal, particles were observed
      by electron microscopy. In nondenaturing PAGE, no difference in the mobility was
      observed between the purified prebeta1-HDL and original plasma prebeta1-HDL, or
      between the prebeta1-HDL and lipid-free apoA-1 prepared by delipidating HDL. In
      sandwich ELISA using two anti-prebeta1-HDL MAbs, reactivity with intact plasma
      prebeta1-HDL was observed in ELISA using two MAbs with distinct epitopes but no
      reactivity was observed in ELISA using a single MAb, and the same phenomenon was
      observed with monomolecular lipid-free apoA-1. These results suggest that plasma
      prebeta1-HDL is lipid-free monomolecular apoA-1. 

PMID- 24304669
TI  - The role of risedronate in osteopenia in Crohn's disease.

PMID- 24304670
TI  - ATG16L1 Crohn's disease risk stresses the endoplasmic reticulum of Paneth cells.

PMID- 24304671
TI  - Marine viruses, a genetic reservoir revealed by targeted viromics.
AB  - Metagenomics has opened new windows on investigating viral diversity and
      functions. Viromic studies typically require large sample volumes and filtration
      through 0.2 MUm pore-size filters, consequently excluding or under-sampling
      tailed and very large viruses. We have optimized a targeted viromic approach that
      employs fluorescence-activated sorting and whole genome amplification to produce
      dsDNA-enriched libraries from discrete viral populations from a 1-ml water
      sample. Using this approach on an environmental sample from the Patagonian Shelf,
      we produced three distinct libraries. One of the virus libraries was dominated
      (79.65% of sequences with known viral homology) by giant viruses from the
      Mimiviridae and Phycodnaviridae families, while the two other viromes were
      dominated by smaller phycodnaviruses, cyanophages and other bacteriophages. The
      estimated genotypic richness and diversity in our sorted viromes, with 52-163
      estimated genotypes, was much lower than in previous virome reports. Fragment
      recruitment of metagenome reads to selected reference viral genomes yields high
      genome coverage, suggesting little amplification and sequencing bias against some
      genomic regions. These results underscore the value of our approach as an
      effective way to target and investigate specific virus groups. In particular, it
      will help reveal the diversity and abundance of giant viruses in marine
      ecosystems. 

PMID- 24304672
TI  - Phage infection of an environmentally relevant marine bacterium alters host
      metabolism and lysate composition.
AB  - Viruses contribute to the mortality of marine microbes, consequentially altering
      biological species composition and system biogeochemistry. Although it is well
      established that host cells provide metabolic resources for virus replication,
      the extent to which infection reshapes host metabolism at a global level and the
      effect of this alteration on the cellular material released following viral lysis
      is less understood. To address this knowledge gap, the growth dynamics,
      metabolism and extracellular lysate of roseophage-infected Sulfitobacter sp. 2047
      was studied using a variety of techniques, including liquid chromatography-tandem
      mass spectrometry (LC-MS/MS)-based metabolomics. Quantitative estimates of the
      total amount of carbon and nitrogen sequestered into particulate biomass indicate
      that phage infection redirects ~75% of nutrients into virions. Intracellular
      concentrations for 82 metabolites were measured at seven time points over the
      infection cycle. By the end of this period, 71% of the detected metabolites were
      significantly elevated in infected populations, and stable isotope-based flux
      measurements showed that these cells had elevated metabolic activity. In contrast
      to simple hypothetical models that assume that extracellular compounds increase
      because of lysis, a profile of metabolites from infected cultures showed that
      >70% of the 56 quantified compounds had decreased concentrations in the lysate
      relative to uninfected controls, suggesting that these small, labile nutrients
      were being utilized by surviving cells. These results indicate that virus
      infected cells are physiologically distinct from their uninfected counterparts,
      which has implications for microbial community ecology and biogeochemistry. 

PMID- 24304673
TI  - Host immune responses accelerate pathogen evolution.
AB  - Pathogens face a hostile and often novel environment when infecting a new host,
      and adaptation is likely to be an important determinant of the success in
      colonization and establishment. We hypothesized that resistant hosts will impose
      stronger selection on pathogens than susceptible hosts, which should accelerate
      pathogen evolution through selection biased toward effector genes. To test this
      hypothesis, we conducted an experimental evolution study on Xanthomonas citri
      subsp. citri (Xcc) in a susceptible plant species and a resistant plant species.
      We performed 55 rounds of repeated reinoculation of Xcc through susceptible host
      grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2,
      K3). Consequently, only K1 and K3 isolates lost their ability to elicit a
      hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and
      descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations
      were biased toward type three secretion system effectors in isolates K1 and K3.
      Parallel evolution was observed in the K1 and K3 strains, suggesting that the
      mutations result from selection rather than by random drift. Our results support
      our hypothesis and suggest that repeated infection of resistant hosts by
      pathogens should be prevented to avoid selecting for adaptive pathogens. 

PMID- 24304674
TI  - Eco-evolutionary feedbacks drive species interactions.
AB  - In the biosphere, many species live in close proximity and can thus interact in
      many different ways. Such interactions are dynamic and fall along a continuum
      between antagonism and cooperation. Because interspecies interactions are the key
      to understanding biological communities, it is important to know how species
      interactions arise and evolve. Here, we show that the feedback between ecological
      and evolutionary processes has a fundamental role in the emergence and dynamics
      of species interaction. Using a two-species artificial community, we demonstrate
      that ecological processes and rapid evolution interact to influence the dynamics
      of the symbiosis between a eukaryote (Saccharomyces cerevisiae) and a bacterium
      (Rhizobium etli). The simplicity of our experimental design enables an explicit
      statement of causality. The niche-constructing activities of the fungus were the
      key ecological process: it allowed the establishment of a commensal relationship
      that switched to ammensalism and provided the selective conditions necessary for
      the adaptive evolution of the bacteria. In this latter state, the bacterial
      population radiates into more than five genotypes that vary with respect to
      nutrient transport, metabolic strategies and global regulation. Evolutionary
      diversification of the bacterial populations has strong effects on the community;
      the nature of interaction subsequently switches from ammensalism to antagonism
      where bacteria promote yeast extinction. Our results demonstrate the importance
      of the evolution-to-ecology pathway in the persistence of interactions and the
      stability of communities. Thus, eco-evolutionary dynamics have the potential to
      transform the structure and functioning of ecosystems. Our results suggest that
      these dynamics should be considered to improve our understanding of beneficial
      and detrimental host-microbe interactions. 

PMID- 24304675
TI  - Surface-motility induction, attraction and hitchhiking between bacterial species
      promote dispersal on solid surfaces.
AB  - The ability to move on solid surfaces provides ecological advantages for
      bacteria, yet many bacterial species lack this trait. We found that Xanthomonas
      spp. overcome this limitation by making use of proficient motile bacteria in
      their vicinity. Using X. perforans and Paenibacillus vortex as models, we show
      that X. perforans induces surface motility, attracts proficient motile bacteria
      and 'rides' them for dispersal. In addition, X. perforans was able to restore
      surface motility of strains that lost this mode of motility under multiple growth
      cycles in the lab. The described interaction occurred both on agar plates and
      tomato leaves and was observed between several xanthomonads and motile bacterial
      species. Thus, suggesting that this motility induction and hitchhiking strategy
      might be widespread and ecologically important. This study provides an example as
      to how bacteria can rely on the abilities of their neighboring species for their
      own benefit, signifying the importance of a communal organization for fitness. 

PMID- 24304676
TI  - Molecular cloning and pharmacological properties of an acidic PLA2 from Bothrops
      pauloensis snake venom.
AB  - In this work, we describe the molecular cloning and pharmacological properties of
      an acidic phospholipase A(2) (PLA(2)) isolated from Bothrops pauloensis snake
      venom. This enzyme, denominated BpPLA(2)-TXI, was purified by four
      chromatographic steps and represents 2.4% of the total snake venom protein
      content. BpPLA(2)-TXI is a monomeric protein with a molecular mass of 13.6 kDa,
      as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF) analysis and its theoretical isoelectric point was
      4.98. BpPLA(2)-TXI was catalytically active and showed some pharmacological
      effects such as inhibition of platelet aggregation induced by collagen or ADP and
      also induced edema and myotoxicity. BpPLA(2)-TXI displayed low cytotoxicity on TG
      180 (CCRF S 180 II) and Ovarian Carcinoma (OVCAR-3), whereas no cytotoxicity was
      found in regard to MEF (Mouse Embryonic Fibroblast) and Sarcoma 180 (TIB-66). The
      N-terminal sequence of forty-eight amino acid residues was determined by Edman
      degradation. In addition, the complete primary structure of 122 amino acids was
      deduced by cDNA from the total RNA of the venom gland using specific primers, and
      it was significantly similar to other acidic D49 PLA(2)s. The phylogenetic
      analyses showed that BpPLA(2)-TXI forms a group with other acidic D49 PLA(2)s
      from the gender Bothrops, which are characterized by a catalytic activity
      associated with anti-platelet effects.

PMID- 24304677
TI  - Probiotic supplementation during pregnancy or infancy for the prevention of
      asthma and wheeze: systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the association of probiotic supplementation during
      pregnancy or infancy with childhood asthma and wheeze. DESIGN: Systematic review
      and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase,
      and Central (Cochrane Library) databases from inception to August 2013, plus the
      World Health Organization's international clinical trials registry platform and
      relevant conference proceedings for the preceding five years. Included trials and
      relevant reviews were forward searched in Web of Science. REVIEW METHODS: Two
      reviewers independently identified randomised controlled trials evaluating
      probiotics administered to mothers during pregnancy or to infants during the
      first year of life. The primary outcome was doctor diagnosed asthma; secondary
      outcomes included wheeze and lower respiratory tract infection. RESULTS: We
      identified 20 eligible trials including 4866 children. Trials were heterogeneous
      in the type and duration of probiotic supplementation, and duration of follow-up.
      Only five trials conducted follow-up beyond participants' age of 6 years (median
      24 months), and none were powered to detect asthma as the primary outcome. The
      overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident
      wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively.
      Among 3257 infants enrolled in nine trials contributing asthma data, the risk
      ratio of doctor diagnosed asthma in participants randomised to receive probiotics
      was 0.99 (95% confidence interval 0.81 to 1.21, I(2)=0%). The risk ratio of
      incident wheeze was 0.97 (0.87 to 1.09, I(2)=0%, 9 trials, 1949 infants). Among
      1364 infants enrolled in six trials, the risk ratio of lower respiratory tract
      infection after probiotic supplementation was 1.26 (0.99 to 1.61, I(2)=0%). We
      adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk
      of bias, mainly due to attrition. CONCLUSIONS: We found no evidence to support a
      protective association between perinatal use of probiotics and doctor diagnosed
      asthma or childhood wheeze. Randomised controlled trials to date have not yielded
      sufficient evidence to recommend probiotics for the primary prevention of these
      disorders. Extended follow-up of existing trials, along with further clinical and
      basic research, are needed to accurately define the role of probiotics in the
      prevention of childhood asthma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      (CRD42013004385).

PMID- 24304678
TI  - Relationships between human vitality and mitochondrial respiratory parameters,
      reactive oxygen species production and dNTP levels in peripheral blood
      mononuclear cells.
AB  - Low vitality (a component of fatigue) in middle-aged and older adults is an
      important complaint often identified as a symptom of a disease state or side
      effect of a treatment. No studies to date have investigated the potential link
      between dysfunctional mitochondrial ATP production and low vitality. Therefore,
      we measured a number of cellular parameters related to mitochondrial activity in
      peripheral blood mononuclear cells (PBMCs) isolated from middle-aged men, and
      tested for association with vitality. These parameters estimate mitochondrial
      respiration, reactive oxygen species (ROS) production, and deoxyribonucleotide
      (dNTP) balance in PBMCs. The population was drawn from the Metropolit cohort of
      men born in 1953. Vitality level was estimated from the Medical Outcomes Study
      Short Form 36 (SF-36) vitality scale. We found that vitality score had no
      association with any of the mitochondrial respiration parameters. However,
      vitality score was inversely associated with cellular ROS production and cellular
      deoxythymidine triphosphate (dTTP) levels and positively associated with
      deoxycytidine triphosphate (dCTP) levels. We conclude that self-reported
      persistent low vitality is not associated with specific aspects of mitochondrial
      oxidative phosphorylation capacity in PBMCs, but may have other underlying
      cellular dysfunctions that contribute to dNTP imbalance and altered ROS
      production. 

PMID- 24304679
TI  - Health-related quality of life in children and adolescents with celiac disease:
      survey of a population from central Italy.
AB  - BACKGROUND: Celiac Disease (CD) is an increasingly common autoimmune disorder. It
      requires a strict lifelong adherence to a gluten-free diet (GFD) which can
      influence health-related quality of life (HRQOL). This study assesses HRQOL in
      children and adolescents with CD and explores how several demographic and
      clinical characteristics and GFD adherence affect their perceived health status.
      METHODS: We recruited 140 consecutive children and adolescents with CD confirmed
      by small bowel biopsy. HRQOL was assessed using the SF-12 questionnaire plus some
      CD-specific questions exploring wellbeing and lifestyle. Patients, aged 10 to 18
      years, were identified by pediatric gastroenterologists and guided in filling out
      the questionnaire by trained psychologists. Parametric or non-parametric tests
      were applied to analyze continuous variables and frequencies as appropriate.
      RESULTS: The SF-12 mean mental component summary score (MCS12) was lower than in
      the general Italian population (p < 0.001), whereas differences in terms of
      physical health were not significant (p = 0.220). More than one third of those
      interviewed reported feeling angry "always" or "most of the time" about having to
      follow the GFD, and nearly 20% reported feeling different from others and
      misunderstood because of CD "always" or "most of the time". CONCLUSIONS: Our
      findings highlight the need for health professionals to identify adolescents with
      major disease-related problems. The food industry should improve its range of
      gluten-free food products and public bodies and institutions should promote
      informative campaigns and help promote the overall quality of life of children
      and adolescents with CD.

PMID- 24304680
TI  - Effect of very low-intensity resistance training with slow movement on muscle
      size and strength in healthy older adults.
AB  - We previously reported that low-intensity [50% of one repetition maximum (1RM)]
      resistance training with slow movement and tonic force generation (LST) causes
      muscle hypertrophy and strength gain in older participants. The aim of this study
      was to determine whether resistance training with slow movement and much more
      reduced intensity (30%1RM) increases muscle size and strength in older adults.
      Eighteen participants (60-77 years) were randomly assigned to two groups. One
      group performed very low-intensity (30% 1RM) knee extension exercise with
      continuous muscle contraction (LST: 3-s eccentric, 3-s concentric, and 1-s
      isometric actions with no rest between each repetition) twice a week for 12
      weeks. The other group underwent intermitted muscle contraction (CON: 1-s
      concentric and 1-s eccentric actions with 1-s rest between each repetition) for
      the same time period. The 1RM, isometric and isokinetic strengths, and cross
      sectional image of the mid-thigh obtained by magnetic resonance imaging were
      examined before and after the intervention. LST significantly increased the cross
      sectional area of the quadriceps muscle (5.0%, P<0.001) and isometric and
      isokinetic knee extension strengths (P<0.05). CON failed to increase muscle size
      (1.1%, P = 0.12), but significantly improved its strength (P<0.05). These results
      indicate that even if the intensity is as low as 30% 1RM, LST can increase muscle
      size and strength in healthy older adults. The large total contraction time may
      be related to muscle hypertrophy and strength gain. LST would be useful for
      preventing sarcopenia in older individuals.

PMID- 24304681
TI  - Analysis of banana transcriptome and global gene expression profiles in banana
      roots in response to infection by race 1 and tropical race 4 of Fusarium
      oxysporum f. sp. cubense.
AB  - BACKGROUND: Cavendish, the most widely grown banana cultivar, is relatively
      resistant to Race 1 of Fusarium oxysporum f. sp. cubense (Foc1) which caused
      widespread Panama disease during the first half of the 20th century but is
      susceptible to Tropical Race 4 of Foc (Foc TR4) which is threatening world banana
      production. The genome of the diploid species Musa acuminata which is the
      ancestor of a majority of triploid banana cultivars has recently been sequenced.
      Availability of banana transcriptomes will be highly useful for improving banana
      genome annotation and for biological research. The knowledge of global gene
      expression patterns influenced by infection of different Foc races will help to
      understand the host responses to the infection. RESULTS: RNA samples from
      different organs of the Cavendish cultivar were pooled for deep sequencing using
      the Illumina technology. Analysis of the banana transcriptome led to
      identification of over 842 genes that were not annotated by the Musa genome
      project. A large number of simple nucleotide polymorphisms (SNPs) and short
      insertions and deletion (indels) were identified from the transcriptome data. GFP
      expressing Foc1 and Foc TR4 were used to monitor the infection process. Both Foc1
      and Foc TR4 were found to be able to invade banana roots and spread to root
      vascular tissues in the first two days following inoculation. Digital gene
      expression (DGE) profiling analysis reveal that the infection by Foc1 and Foc TR4
      caused very similar changes in the global gene expression profiles in the banana
      roots during the first two days of infection. The Foc infection led to induction
      of many well-known defense-related genes. Two genes encoding the ethylene
      biosynthetic enzyme ACC oxidase and several ethylene-responsive transcription
      factors (ERF) were among the strongly induced genes by both Foc1 and Foc TR4.
      CONCLUSIONS: Both Foc1 and Foc TR4 are able to spread into the vascular system of
      banana roots during the early infection process and their infection led to
      similar gene expression profiles in banana roots. The transcriptome profiling
      analysis indicates that the ethylene synthetic and signalling pathways were
      activated in response to the Foc infection.

PMID- 24304682
TI  - Gender differences in suicidal behaviour in patients with first-episode
      psychosis.
AB  - AIM: Prior research shows contradictory gender patterns in suicidal behaviour
      among patients with first-episode psychosis. The aim of this study was to
      investigate gender differences in the prevalence of suicidal behaviour (suicidal
      ideation, suicide plans and suicide attempts) and to delineate risk factors for
      suicidal behaviour among consecutively included male and female patients with
      first-episode psychosis in the TIPS II early detection study. METHODS: Patients
      with first-episode psychosis (n = 246) from a hospital catchment area with a
      system for early detection were assessed and compared on baseline
      sociodemographical and clinical variables according to gender. Current (past 1
      month) and lifetime prevalence of suicidal behaviour were assessed. RESULTS:
      Current and lifetime rates of suicidal behaviour were high (50.8% and 65.9%,
      respectively) and higher among females (lifetime: 78.3 %, past month: 64.2 %)
      versus males (lifetime: 56.4 %, past month: 40.7 %). Depressive symptoms and
      female gender were associated with both lifetime and current risk for suicidal
      behaviour. Lifetime prevalence was also associated with a longer duration of
      untreated psychosis and young age after controlling for other risk factors.
      CONCLUSIONS: Suicidal behaviour was frequent among patients with first-episode
      psychosis, with a higher prevalence of suicidal behaviour in females. Depressive
      symptoms and female gender were significantly associated with suicidal behaviour.

PMID- 24304683
TI  - Post-immobilization eccentric training promotes greater hypertrophic and
      angiogenic responses than passive stretching in muscles of weanling rats.
AB  - This study investigated how different types of remobilization after hind limb
      immobilization, eccentric exercise and passive static stretching, influenced the
      adaptive responses of muscles with similar function and fascicle size, but
      differing in their contractile characteristics. Female Wistar weanling rats (21
      days old) were divided into 8 groups: immobilized for 10 days, maintaining the
      ankle in maximum plantar flexion; immobilized and submitted to eccentric training
      for 10 or 21 days on a declining treadmill for 40min; immobilized and submitted
      to passive stretching for 10 or 21 days for 40min by maintaining the ankle in
      maximum dorsiflexion; control of immobilized; and control of 10 or 21 days. The
      soleus and plantaris muscles were analyzed using fiber distribution, lesser
      diameter, capillary/fiber ratio, and morphology. Results showed that the
      immobilization reduced the diameter of all fiber types, caused changes in fiber
      distribution and decreased the number of transverse capillaries in both muscles.
      The recovery period of the soleus muscle is longer than that of the plantaris
      after detraining. Moreover, eccentric training induced greater hypertrophic and
      angiogenic responses than passive stretching, especially after 21 days of
      rehabilitation. Both techniques demonstrated positive effects for muscle
      rehabilitation with the eccentric exercise being more effective. 

PMID- 24304684
TI  - Enhancement of ovarian tumor detection with alphavbeta3 integrin-targeted
      ultrasound molecular imaging agent in laying hens: a preclinical model of
      spontaneous ovarian cancer.
AB  - OBJECTIVE: Because of the lack of an effective early detection test, ovarian
      cancer (OVCA) in most cases is detected at late stages and remains a fatal
      gynecological malignancy. Molecular imaging provides information on the changes
      associated with the development of a disease at molecular levels. Because
      angiogenesis is an early event in tumor development, increased expression of
      alphavbeta3 integrins by ovarian tumor-associated angiogenic microvessels
      provides a target for noninvasive ultrasound imaging to detect early-stage OVCA.
      The goal of this study was to examine the feasibility of alphavbeta3 integrin
      targeted molecular imaging agent in enhancing the detection of spontaneous
      ovarian tumor in laying hens, a preclinical model of OVCA. METHODS: The study was
      conducted in 2 phases, including a cross-sectional exploratory followed by a
      prospective monitoring of hens for 45 weeks with targeted ultrasound imaging.
      Changes in ultrasound signal intensity were determined before and after the
      injection of alphavbeta3 integrin-targeted imaging agent in hens with spontaneous
      OVCA. All images were digitally stored. After scanning, ovarian tissues from all
      hens were collected and processed for histopathologic and immunohistochemical
      studies. RESULTS: Ultrasound signal intensity was significantly (P < 0.001)
      higher in hens with early-stage OVCA than in normal hens and increased further in
      late-stage OVCA. Compared with that in normal cases, ultrasound signal
      intensities increased approximately 19-fold in early stage and 26-fold in late
      stage OVCA. Differences in signal enhancement were not observed among different
      histologic subtypes of OVCA. Higher signal intensities from targeted imaging of
      ovarian tumors were associated with increased number of alphavbeta3 integrin
      expressing ovarian microvessels. Prospective monitoring of hens with alphavbeta3
      integrin-targeted imaging agent detected OVCA at early stage. CONCLUSIONS: These
      results suggest that alphavbeta3 integrin-targeted imaging agent enhanced the
      visualization of ovarian tumor-associated angiogenic microvessels in hens with
      early-stage OVCA and may form a foundation for clinical studies.

PMID- 24304685
TI  - Differences in LINE-1 methylation between endometriotic ovarian cyst and
      endometriosis-associated ovarian cancer.
AB  - BACKGROUND: Endometriosis in endometriosis-associated ovarian cancer (EAOC)
      refers to lesions that can derive from endometriotic ovarian cysts (ECs) that
      form in the ovarian endometrium with the potential to transform into full-blown
      ovarian cancer. Hypomethylation of long interspersed element-1 (LINE-1 or L1) is
      a common epigenomic event in several cancers and is strongly associated with
      ovarian cancer progression. OBJECTIVES: To evaluated alterations in LINE-1
      methylation between EC, ovarian endometrioid adenocarcinoma (OEA), EAOC, and
      ovarian clear cell carcinoma (OCC). METHODS/ MATERIALS: First, LINE-1 methylation
      status in 19 normal endometrium, 29 EC, 35 OCC, and 22 OEA tissues from unrelated
      samples were compared. Then, specific areas of eutopic endometrium, contiguous
      endometriosis, and cancer arising from 16 EAOCs were collected by microdissection
      and analyzed for LINE-1 methylation status. RESULTS: The total LINE-1 methylation
      levels were significantly different among the endometrium, endometriosis, and
      ovarian cancer (P < 0.001). A stepwise decrease in LINE-1 methylation was
      observed in the following order: normal endometrium, EC, OEA, and OCC.
      Interestingly, endometriosis in EAOC of both OEA (P = 0.016) and OCC (P = 0.003)
      possessed a higher percentage of LINE-1 unmethylated loci than EC. CONCLUSION:
      Our data implicate that LINE-1 hypomethylation is an early molecular event
      involved in OEA and OCC malignant transformation. Precise measurements of LINE-1
      methylation may help to distinguish EC and endometriosis in EAOC.

PMID- 24304686
TI  - Increase of mesenchymal stem cell migration by cannabidiol via activation of
      p42/44 MAPK.
AB  - Migration and differentiation of mesenchymal stem cells (MSCs) are known to be
      involved in various regenerative processes such as bone healing. However, little
      is known about the pharmacotherapeutical options aiming at the mobilization and
      differentiation of MSCs. The present study therefore focussed on cannabinoids
      which have been demonstrated to exhibit tissue healing properties. Using Boyden
      chamber assays, the non-psychoactive phytocannabinoid cannabidiol (CBD) was found
      to increase the migration of adipose-derived MSCs in a time- and concentration
      dependent manner. CBD-induced migration was inhibited by AM-630 (CB2 receptor
      antagonist) and O-1602 (G protein-coupled receptor 55 [GRP55] agonist). Moreover,
      the promigratory effect of CBD was antagonized by inhibition of the p42/44
      mitogen-activated protein kinase (MAPK) pathway which became activated upon CBD
      treatment. In line with this data, AM-630 and O-1602 attenuated CBD-induced
      p42/44 MAPK phosphorylation. A p42/44 MAPK-dependent promigratory effect was
      likewise demonstrated for the GPR55 antagonist O-1918 and the selective CB2
      receptor agonist JWH-133. Additional evidence for a functional effect of CBD on
      MSCs was provided by experiments demonstrating long-term stimulation with CBD to
      induce differentiation of MSCs into the osteoblastic lineage as evidenced by
      increased mineralization assessed by cresolphthalein complexone assay and
      enhanced activity of alkaline phosphatase. Collectively, this study demonstrates
      CBD to promote the migration of MSCs via activation of the CB2 receptor and
      inhibition of GPR55 and to induce osteoblastic differentiation. CBD may therefore
      recruit MSCs to sites of calcifying tissue regeneration and subsequently support
      bone regeneration via an osteoanabolic action on MSCs.

PMID- 24304687
TI  - The end of Alzheimer's disease--from biochemical pharmacology to
      ecopsychosociology: a personal perspective.
AB  - The future of the Alzheimer's disease (AD) field involves a more complete
      understanding not only the state of current scientific approaches, but also the
      linguistic and cultural context of preclinical and clinical research and policy
      activities. The challenges surrounding dementia are large and growing but are
      only part of broader social and health concerns. In this latter context, the
      current state of research in the AD area is reviewed together with necessary
      priorities in moving forward. Creating a more optimistic future will depend less
      on genetic and reductionist approaches and more on environmental and
      intergenerative approaches that will aid in recalibrating the study of AD from an
      almost exclusive focus on biochemical, molecular and genetic aspects to better
      encompass "real world" ecological and psychosocial models of health. 

PMID- 24304688
TI  - PGC-1alpha supports glutamine metabolism in breast cancer.
AB  - BACKGROUND: Glutamine metabolism is a central metabolic pathway in cancer.
      Recently, reductive carboxylation of glutamine for lipogenesis has been shown to
      constitute a key anabolic route in cancer cells. However, little is known
      regarding central regulators of the various glutamine metabolic pathways in
      cancer cells. METHODS: The impact of PGC-1alpha and ERRalpha on glutamine enzyme
      expression was assessed in ERBB2+ breast cancer cell lines with quantitative RT
      PCR, chromatin immunoprecipitation, and immunoblotting experiments. Glutamine
      flux was quantified using 13C-labeled glutamine and GC/MS analyses. Functional
      assays for lipogenesis were performed using 14C-labeled glutamine. The expression
      of glutamine metabolism genes in breast cancer patients was determined by
      bioinformatics analyses using The Cancer Genome Atlas. RESULTS: We show that the
      transcriptional coactivator PGC-1alpha, along with the transcription factor
      ERRalpha, is a positive regulator of the expression of glutamine metabolism genes
      in ERBB2+ breast cancer. Indeed, ERBB2+ breast cancer cells with increased
      expression of PGC-1alpha display elevated expression of glutamine metabolism
      genes. Furthermore, ERBB2+ breast cancer cells with reduced expression of PGC
      1alpha or when treated with C29, a pharmacological inhibitor of ERRalpha, exhibit
      diminished expression of glutamine metabolism genes. The biological relevance of
      the control of glutamine metabolism genes by the PGC-1alpha/ERRalpha axis is
      demonstrated by consequent regulation of glutamine flux through the citric acid
      cycle. PGC-1alpha and ERRalpha regulate both the canonical citric acid cycle
      (forward) and the reductive carboxylation (reverse) fluxes; the latter can be
      used to support de novo lipogenesis reactions, most notably in hypoxic
      conditions. Importantly, murine and human ERBB2+ cells lines display a
      significant dependence on glutamine availability for their growth. Finally, we
      show that PGC-1alpha expression is positively correlated with that of the
      glutamine pathway in ERBB2+ breast cancer patients, and high expression of this
      pathway is associated with reduced patient survival. CONCLUSIONS: These data
      reveal that the PGC-1alpha/ERRalpha axis is a central regulator of glutamine
      metabolism in ERBB2+ breast cancer. This novel regulatory link, as well as the
      marked reduction in patient survival time associated with increased glutamine
      pathway gene expression, suggests that targeting glutamine metabolism may have
      therapeutic potential in the treatment of ERBB2+ breast cancer.

PMID- 24304689
TI  - The feasibility and acceptability of conducting a trial of specialist medical
      care and the Lightning Process in children with chronic fatigue syndrome:
      feasibility randomized controlled trial (SMILE study).
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is
      relatively common in children with limited evidence for treatment. The Phil
      Parker Lightning Process (LP) is a trademarked intervention, which >250 children
      use annually. There are no reported studies investigating the effectiveness or
      possible side effects of LP. METHODS: The trial population was drawn from the
      Bath and Bristol NHS specialist paediatric CFS or ME service. The study was
      designed as a pilot randomized trial with children (aged 12 to 18 years)
      comparing specialist medical care with specialist medical care plus the Lightning
      Process. Integrated qualitative methodology was used to explore the feasibility
      and acceptability of the recruitment, randomization and interventions. RESULTS: A
      total of 56 children were recruited from 156 eligible children (1 October 2010 to
      16 June 2012). Recruitment, randomization and both interventions were feasible
      and acceptable. Participants suggested changes to improve feasibility and
      acceptability and we incorporated the following in the trial protocol: stopped
      collecting 6-week outcomes; introduced a second reminder letter; used phone calls
      to collect primary outcomes from nonresponders; informed participants about
      different approaches of each intervention and changed our recommendation for the
      primary outcome for the full study from school attendance to disability (SF-36
      physical function subscale) and fatigue (Chalder Fatigue Scale). CONCLUSIONS:
      Conducting randomized controlled trials (RCTs) to investigate an alternative
      treatment such as LP is feasible and acceptable for children with CFS or ME.
      Feasibility studies that incorporate qualitative methodology enable changes to be
      made to trial protocols to improve acceptability to participants. This is likely
      to improve recruitment rate and trial retention. TRIAL REGISTRATION: Feasibility
      study first randomization: 29 September 2010. Trial registration: Current
      Controlled Trials ISRCTN81456207 (31 July 2012). Full trial first randomization:
      19 September 2012.

PMID- 24304690
TI  - Invasive cancer cells and metastasis. Preface.

PMID- 24304691
TI  - Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft
      model.
AB  - Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing
      to metastatic disease. The purpose of this study was to evaluate the effects of
      the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and
      on canine osteosarcoma growth and metastasis in a mouse xenograft model. We
      hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor
      cellular proliferation, tumor growth, and metastasis. After performing clonogenic
      assays, aurothiomalate or a placebo was administered to 54 mice inoculated with
      canine osteosarcoma. Survival, tumor growth, embolization, metastasis,
      histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3
      were compared between groups. Statistical analysis was carried out using the
      Kaplan-Meier method with the log-rank test and one-way analysis of variance with
      the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent
      inhibition of osteosarcoma cell survival (P<0.001) and decreased tumor growth
      (P<0.001). Pulmonary macrometastasis and Ki67 labeling were reduced with low-dose
      aurothiomalate (P=0.033 and 0.005, respectively), and tumor emboli and pulmonary
      micrometastases were decreased with high-dose aurothiomalate (P=0.010 and 0.011,
      respectively). There was no difference in survival, tumor development,
      ulceration, mitotic indices, tumor necrosis, nonpulmonary metastases, and caspase
      3 labeling. Aurothiomalate treatment inhibited osteosarcoma cell survival and
      reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis.
      Given aurothiomalate's established utility in canine and human medicine, our
      results suggest that this compound may hold promise as an adjunctive therapy for
      osteosarcoma. Further translational research is warranted to better characterize
      the dose response of canine and human osteosarcoma to aurothiomalate. 

PMID- 24304693
TI  - Identification of a novel component C2ORF3 in the lariat-intron complex: lack of
      C2ORF3 interferes with pre-mRNA splicing via intron turnover pathway.
AB  - To identify the novel factors involved in the postsplicing intron turnover
      pathway, we carried out immunoprecipitation with known postsplicing factors,
      hPrp43 and TFIP11. As an interacting factor, we identified C2ORF3 protein by mass
      spectrometry. We found that C2ORF3 protein is present in the previously
      characterized Intron Large (IL) complex with an excised lariat intron. In vitro
      splicing using C2ORF3-depleted nuclear extracts showed significant repression of
      splicing, suggesting that C2ORF3 protein is required for pre-mRNA splicing
      through its presumable role in efficient intron turnover. Interestingly, C2ORF3
      protein is localized in both the nucleoplasm and nucleoli, which suggests a
      potential function in rRNA processing. 

PMID- 24304692
TI  - The case for the continuing use of the revised Cambridge Reference Sequence
      (rCRS) and the standardization of notation in human mitochondrial DNA studies.
AB  - Since the determination in 1981 of the sequence of the human mitochondrial DNA
      (mtDNA) genome, the Cambridge Reference Sequence (CRS), has been used as the
      reference sequence to annotate mtDNA in molecular anthropology, forensic science
      and medical genetics. The CRS was eventually upgraded to the revised version
      (rCRS) in 1999. This reference sequence is a convenient device for recording
      mtDNA variation, although it has often been misunderstood as a wild-type (WT) or
      consensus sequence by medical geneticists. Recently, there has been a proposal to
      replace the rCRS with the so-called Reconstructed Sapiens Reference Sequence
      (RSRS). Even if it had been estimated accurately, the RSRS would be a cumbersome
      substitute for the rCRS, as the new proposal fuses--and thus confuses--the two
      distinct concepts of ancestral lineage and reference point for human mtDNA.
      Instead, we prefer to maintain the rCRS and to report mtDNA profiles by employing
      the hitherto predominant circumfix style. Tree diagrams could display mutations
      by using either the profile notation (in conventional short forms where
      appropriate) or in a root-upwards way with two suffixes indicating ancestral and
      derived nucleotides. This would guard against misunderstandings about reporting
      mtDNA variation. It is therefore neither necessary nor sensible to change the
      present reference sequence, the rCRS, in any way. The proposed switch to RSRS
      would inevitably lead to notational chaos, mistakes and misinterpretations.

PMID- 24304695
TI  - Translation, cross-cultural adaptation and validation of the French version of
      the Knee Outcome Survey-Activities of Daily Living Scale.
AB  - PURPOSE: The Activities of Daily Living Scale of the Knee Outcome Survey (KOS
      ADLS) is a joint-specific questionnaire measuring functional limitation
      experienced by individuals with knee disorders. The original English version of
      the KOS-ADLS has been shown to be highly reliable and responsive to change. The
      purpose of this study was to perform a translation and cross-cultural adaptation
      of the original version of the KOS-ADLS questionnaire into French and to validate
      this French version of the questionnaire. METHOD: In accordance with standard
      procedure, the original version of the KOS-ADLS was translated and cross
      culturally adapted into French. Once the final French version of the KOS-ADLS was
      developed, it was subjected to further psychometric evaluation with 76
      individuals with knee disorders. Each participant completed the KOS-ADLS on three
      occasions: at baseline, two days later to evaluate test-retest reliability, and
      four weeks later to evaluate responsiveness. Symptoms and function-oriented
      construct questions were also completed to evaluate construct-convergent and
      known-group validity. RESULTS: The cross-cultural adaptation procedure revealed
      no major problems with content or language. The French version of the KOS-ADLS
      showed excellent test-retest reliability with low measurement error (intraclass
      correlation coefficient = 0.92, minimal detectable change = 8.3), as well as high
      responsiveness (standardized response mean = 1.41; clinically important
      difference = 13.6). Further, it discriminates between different levels of self
      rated or clinician-rated knee function. CONCLUSIONS: The French version of the
      KOS-ADLS is a reliable, valid and responsive questionnaire for the assessment of
      functional limitation in individuals with musculoskeletal knee disorders.

PMID- 24304694
TI  - Targeting cell migration and the endoplasmic reticulum stress response with
      calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62
      gene silencing in human tumor cells.
AB  - BACKGROUND: Tumor cells benefit from their ability to avoid apoptosis and invade
      other tissues. The endoplasmic reticulum (ER) membrane protein Sec62 is a key
      player in these processes. Sec62 is essential for cell migration and protects
      tumor cells against thapsigargin-induced ER stress, which are both linked to
      cytosolic Ca2+. SEC62 silencing leads to elevated cytosolic Ca2+ and increased ER
      Ca2+ leakage after thapsigargin treatment. Sec62 protein levels are significantly
      increased in different tumors, including prostate, lung and thyroid cancer.
      METHODS: In lung cancer, the influence of Sec62 protein levels on patient
      survival was analyzed using the Kaplan-Meier method and log-rank test. To
      elucidate the underlying pathophysiological functions of Sec62, Ca2+ imaging
      techniques, real-time cell analysis and cell migration assays were performed. The
      effects of treatment with the calmodulin antagonists, trifluoperazine (TFP) and
      ophiobolin A, on cellular Ca2+ homeostasis, cell growth and cell migration were
      compared with the effects of siRNA-mediated Sec62 depletion or the expression of
      a mutated SEC62 variant in vitro. Using Biacore analysis we examined the Ca2+
      sensitive interaction of Sec62 with the Sec61 complex. RESULTS: Sec62
      overproduction significantly correlated with reduced patient survival. Therefore,
      Sec62 is not only a predictive marker for this type of tumor, but also an
      interesting therapeutic target. The present study suggests a regulatory function
      for Sec62 in the major Ca2+ leakage channel in the ER, Sec61, by a direct and
      Ca2+-sensitive interaction. A Ca2+-binding motif in Sec62 is essential for its
      molecular function. Treatment of cells with calmodulin antagonists mimicked Sec62
      depletion by inhibiting cell migration and rendering the cells sensitive to
      thapsigargin treatment. CONCLUSIONS: Targeting tumors that overproduce Sec62 with
      calmodulin antagonists in combination with targeted thapsigargin analogues may
      offer novel personalized therapeutic options.

PMID- 24304696
TI  - Molecular characterization of major structural protein genes of avian coronavirus
      infectious bronchitis virus isolates in southern china.
AB  - To gain comprehensive genetic information of circulating avian coronavirus
      infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic
      tree, entropy of the amino acid sequences, and the positive selection as well as
      computational recombinations of S1, M and N genes of 23 IBV isolates was
      conducted in the present study. The phylogenetic trees based on the S1, M and N
      genes exhibited considerably different topology and the CK/CH/LSC/99I-type
      isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene.
      Results of entropy of amino acid sequences revealed that the S1 gene had the
      largest variation; the M gene had less variation than the N gene. Positive
      selections were detected in not only S1 but also M and N gene proteins. In
      addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I
      type field isolate were confirmed. In conclusion, multiple IBV genotypes co
      circulated; genetic diversity and positive selections existed in S1, M and N
      genes; 4/91 vaccine recombinants emerged in China. Our results show that field
      IBVs in China are continuing to evolve and vaccine strains may have an important
      role in the appearance of new IBV strains via recombination. In addition, the
      present study indicates that IBV evolution is driven by both generations of
      genetic diversity and selection. 

PMID- 24304697
TI  - Development of a flow-fluorescence in situ hybridization protocol for the
      analysis of microbial communities in anaerobic fermentation liquor.
AB  - BACKGROUND: The production of bio-methane from renewable raw material is of high
      interest because of the increasing scarcity of fossil fuels. The process of
      biomethanation is based on the inter- and intraspecific metabolic activity of a
      highly diverse and dynamic microbial community. The community structure of the
      microbial biocenosis varies between different biogas reactors and the knowledge
      about these microbial communities is still fragmentary. However, up to now no
      approaches are available allowing a fast and reliable access to the microbial
      community structure. Hence, the aim of this study was to originate a Flow-FISH
      protocol, namely a combination of flow cytometry and fluorescence in situ
      hybridization, for the analysis of the metabolically active microorganisms in
      biogas reactor samples. With respect to the heterogenic texture of biogas reactor
      samples and to collect all cells including those of cell aggregates and biofilms
      the development of a preceding purification procedure was indispensable. RESULTS:
      Six different purification procedures with in total 29 modifications were tested.
      The optimized purification procedure combines the use of the detergent sodium
      hexametaphosphate with ultrasonic treatment and a final filtration step. By this
      treatment, the detachment of microbial cells from particles as well as the
      disbandment of cell aggregates was obtained at minimized cell loss. A Flow-FISH
      protocol was developed avoiding dehydration and minimizing centrifugation steps.
      In the exemplary application of this protocol on pure cultures as well as biogas
      reactor samples high hybridization rates were achieved for commonly established
      domain specific oligonucleotide probes enabling the specific detection of
      metabolically active bacteria and archaea. Cross hybridization and
      autofluorescence effects could be excluded by the use of a nonsense probe and
      negative controls, respectively. CONCLUSIONS: The approach described in this
      study enables for the first time the analysis of the metabolically active
      fraction of the microbial communities within biogas reactors by Flow-FISH.

PMID- 24304698
TI  - Risk perceptions of STIs/HIV and sexual risk behaviours among sexually
      experienced adolescents in the northern part of Lao PDR.
AB  - BACKGROUND: Young people in Laos are more vulnerable to STIs/HIV due to their
      sexual risk behaviours, low perceptions of risk and their socio-cultural
      environments. Perceived risk of contracting STIs/HIV is crucial for the
      assessment of their risk regarding their actual sexual risk behaviors. Thus, the
      objective of this paper is to explore perceptions of risk related to STIs/HIV and
      identify factors associated with this perceived risk among adolescents. METHODS:
      This was a cross sectional study of sexually experienced adolescents aged 14 to
      19 years old in the Luangnamtha province. The multistage sampling techniques were
      used for selecting 1008 adolescents aged 14-19 years old. Of these, 483
      respondents reported having had sexual experience was selected for analysis.
      Univariate and Logistic regression were performed. RESULT: Six per cent of
      respondents reported ever having had anal sex. Slightly less than two thirds
      initiated their first sexual intercourse before age 15. Two thirds of the
      sexually experienced males reported two or more sexual partners during their
      lifetime with the mean 3.1+3.65 while only twelve per cent of girls reported this
      cumulative number of partners. Slightly more than half (57.6%) regarded
      themselves to have no risk at all with 17.2 per cent considered themselves to
      have low risk. Respondents had poor knowledge on STIs/HIV. Factors associated
      with risk perception of getting STIs were: being male, high level of knowledge
      about STIs and having had symptoms of STIs in last six months. Perceived risk of
      getting HIV was significantly associated with being male, having more knowledge
      about STIs and HIV. CONCLUSION: Adolescents in this study engaged in sexual risk
      behaviours, but they have low perception of risk getting STI/HIV. Socio
      demographic factors, knowledge of STIs/HIV, and the level of exposure to STIs
      were the main determinants of the risk perception of STIs/HIV. Our finding
      supports the need to target adolescents in Luangnamtha province for HIV
      prevention intervention by addressing inaccurate perception of risk and
      increasing their knowledge on STIs/HIV.

PMID- 24304699
TI  - First observation in a non-endemic country (Togo) of Penicillium marneffei
      infection in a human immunodeficiency virus-infected patient: a case report.
AB  - BACKGROUND: Infection with Penicillium marneffei is a common opportunistic
      infection in Southeast Asia where it is endemic. We report a case of Penicillium
      marneffei infection with fatal outcome in a Togolese woman infected with Human
      Immunodeficiency Virus (HIV). CASE PRESENTATION: A 45-years-old patient, infected
      with Human Immunodeficiency Virus had consulted for ongoing febrile pneumonia
      since two weeks. Clinical examination revealed fever of 38.5 degrees C, dyspnea,
      pulmonary syndrome condensation and papulo-nodular of "molluscum contagiosum"
      like lesions located on the face, arms, neck and trunk. Sputum smear was negative
      for tuberculosis. The chest radiograph showed reticulonodular opacities in the
      right upper and middle lobes and two caves in the right hilar region. The CD4
      count was 6 cells/mm3 after a year of antiretroviral treatment (Zidovudine
      Lamivudine-Efavirenz). She was treated as smear negative pulmonary tuberculosis
      after a lack of gentamicin and amoxicillin plus clavulanic acid response. Culture
      of skin samples and sputum had revealed the presence of P. marneffei. A treatment
      with ketoconazole 600 mg per day was initiated. After two weeks of treatment,
      there was a decrease in the size and number of papules and nodules, without any
      new lesions. We noted disappearance of cough and fever. The chest X-ray showed a
      decrease of pulmonary lesions. There was no reactivation of P. marneffei
      infection but the patient died from AIDS after two years of follow up.
      CONCLUSION: We report a case of P. marneffei infection in a HIV-infected patient
      in a non-endemic country. Clinicians should think of P. marneffei infection in
      all HIV-infected patients with "molluscum contagiosum" like lesions.

PMID- 24304700
TI  - First report of femtosecond laser cataract surgery in a nanophthalmic eye.

PMID- 24304701
TI  - Cuts to the Office for National Statistics will damage the health of the nation.

PMID- 24304702
TI  - Insertion of long interspersed element-1 in the Mitf gene is associated with
      altered neurobehavior of the black-eyed white Mitf(mi-bw) mouse.
AB  - Microphthalmia-associated transcription factor (Mitf) is required for the
      differentiation of melanoblasts of the neural crest origin. The mouse homozygous
      for the black-eyed white (Mitf(mi-bw) ) allele is characterized by white-coat
      color and deafness with black eye, due to the loss of melanoblasts during
      embryonic development. The Mitf(mi-bw) allele carries an insertion of long
      interspersed element-1 (L1) in intron 3 of the Mitf gene, which may cause the
      deficiency of melanocyte-specific Mitf-M. Here, we show that the L1 insertion
      results in the generation of alternatively spliced Mitf-M mRNA species, such as
      Mitf-M mRNA lacking exon 3, exon 4 or both exons 3 and 4, each of which encodes
      Mitf-M protein with an internal deletion. Transient expression assays showed the
      loss of or reduction in function of each aberrant Mitf-M protein and the dominant
      negative effect of Mitf-M lacking exon 4 that encodes an activation domain. Thus,
      the L1 insertion may decrease the expression level of functional Mitf-M.
      Importantly, Mitf-M mRNA is expressed in the wild-type mouse brain, with the
      highest expression level in the hypothalamus. Likewise, aberrant Mitf-M mRNAs are
      expressed in the bw mouse brain. The bw mice show the altered neurobehavior under
      a stressful environment, suggesting the role of Mitf-M in sensory perception.

PMID- 24304703
TI  - Doubling time calculations for lung cancer by three-dimensional computer-aided
      volumetry: effects of inter-observer differences and nodule characteristics.
AB  - INTRODUCTION: The purpose of this study was to investigate doubling time (DT)
      differences among solid, part-solid (PS) and non-solid (NS) types of lung
      cancers. We also compared inter-observer differences in size measurements between
      diameter and three-dimensional (3D) volume measurements of lung cancers,
      including PS- and NS-type nodules, using 3D computer-aided volumetry (3D-CAV).
      METHODS: The long-axis diameters and 3D volumes of lung tumours were measured
      using CAV by two chest radiologists for 71 consecutive patients with peripheral
      lung cancer who underwent at least two CT examinations before surgical resection.
      We evaluated the inter-observer variability for the ratio of diameter change
      (RCdiameter) and volume change (RCvolume), which were based on two CT images
      obtained at different times prior to resection. Inter-observer agreement was
      evaluated by Bland-Altman plots. Based on the volumes obtained from 3D-CAV, we
      calculated the DTs and compared DT differences between solid, PS and NS types of
      lung tumours. RESULTS: The inter-observer Spearman's rank correlation
      coefficients were 0.87 for RCvolume and 0.64 for RCdiameter (p < 0.001). For all
      internal appearance types, the rs values for RCvolume were greater than those for
      RCdiameter. The median DT values for solid, PS and NS were 278, 347 and 584 days,
      respectively. NS- and PS-type tumours had significantly longer DTs (p = 0.024; by
      Spearman's rank correlation coefficient). CONCLUSIONS: DT determinations using 3D
      CAV had good correlations with the internal appearances of lung cancers. Lung
      tumour volume measurements by 3D-CAV exhibited better inter-observer correlations
      than did diameter measurements.

PMID- 24304704
TI  - Obesity, knee osteoarthritis and knee arthroplasty: a review.
AB  - The incidence of obesity is rising worldwide. Obesity is a risk factor for
      developing osteoarthritis in the knee. Obesity and knee osteoarthritis are
      independently disabling conditions and in combination pose difficult therapeutic
      challenges. This review will discuss obesity, osteoarthritis, and the problems
      associated with knee osteoarthritis in an obese population. Treatment options
      including surgery and its success will be discussed. 

PMID- 24304705
TI  - Theorising sexual media and sexual violence in a forensic setting: men's talk
      about pornography and offending.
AB  - This article reports findings from a discourse analytic study which critically
      explored the language of mental health nurses, and detained sexual offenders, in
      relation to pornography in one high-security hospital. It recognised previous
      empirical investigation, and pro-feminist theorising, into mediated
      representations and male sexual violence, but situated the research process in a
      forensic nursing context. Decision-making about access to, or restriction of,
      commercial sexual literature, as a component of therapeutic intervention and
      offender management, reveals tensions between service-user rights and treatment
      goals. The aim was to access nurse and patient talk in a specific culture. Semi
      structured interviews with eighteen nursing staff, and nine patients, were used
      to co-construct accounts of pornography, sexual offending, and treatment.
      Analysis and data collection were undertaken concurrently. Interviews were audio
      taped and transcribed. Data was coded to identify theoretical/conceptual themes
      and sub-themes representing discursive repertoires. Attention was given to how
      textual variation positioned respondents in relation to each other and the
      institution. Findings suggested collective male talk textured the environment,
      promoted gendered inequality, marginalised female nurses, and undermined
      rehabilitation. Shared discourse enabled male staff and patients to relate to
      each other as men, while maintaining distance through constructions of otherness.
      Discussion focuses on discriminatory discursive-practices, where men's talk about
      pornography and sexual violence embodied gendered knowledge/experience and
      contributed to a toxic culture. Consideration is given to ways of resisting
      institutional impediments and promoting positive therapeutic relations. 

PMID- 24304706
TI  - Strengthening research capacity through the medical education partnership
      initiative: the Mozambique experience.
AB  - BACKGROUND: Since Mozambique's independence, the major emphasis of its higher
      educational institutions has been on didactic education. Because of fiscal and
      human resource constraints, basic and applied research activities have been
      relatively modest in scope, and priorities have often been set primarily by
      external collaborators. These factors have compromised the scope and the
      relevance of locally conducted research and have limited the impact of
      Mozambique's universities as major catalysts for national development. CASE
      DESCRIPTION: We developed a multi-institutional partnership to undertake a
      comprehensive analysis of the research environment at Mozambique's major public
      universities to identify factors that have served as barriers to the development
      of a robust research enterprise. Based on this analysis, we developed a
      multifaceted plan to reduce the impact of these barriers and to enhance research
      capacity within Mozambique. INTERVENTIONS: On the basis of our needs assessment,
      we have implemented a number of major initiatives within participating
      institutions to facilitate basic and applied research activities. These have
      included specialized training programmes, a reorganization of the research
      administration infrastructure, the development of multiple collaborative research
      projects that have emphasized local research priorities and a substantial
      investment in bioinformatics. We have established a research support centre that
      provides grant development and management services to Mozambique's public
      universities and have developed an independent Institutional Review Board for the
      review of research involving human research subjects. Multiple research projects
      involving both communicable and non-communicable diseases have been developed and
      substantial external research support has been obtained to undertake these
      projects. A sizable investment in biomedical informatics has enhanced both
      connectivity and access to digital reference material. Active engagement with
      relevant entities within the Government of Mozambique has aligned institutional
      development with national priorities. CONCLUSIONS: Although multiple challenges
      remain, over the past 3 years significant progress has been made towards
      establishing conditions within which a broad range of basic, translational and
      clinical and public health research can be undertaken. Ongoing development of
      this research enterprise will enhance capacity to address critical locally
      relevant research questions and will leverage resources to accelerate the
      development of Mozambique's national universities.

PMID- 24304707
TI  - An ongoing national intervention to contain the spread of carbapenem-resistant
      enterobacteriaceae.
AB  - In 2007, the Israel Ministry of Health initiated a nationwide intervention aimed
      at containing the spread of carbapenem-resistant Enterobacteriaceae (CRE),
      primarily manifested by the rapid dissemination of a single clone of Klebsiella
      pneumoniae. Data were gathered from acute and long-term care facilities, and ward
      based mandatory guidelines for carrier isolation, patient and staff cohorting,
      and active surveillance were issued. Guidelines were issued to the microbiology
      laboratories delineating procedures for identifying CRE and carbapenemase
      production. A protocol for ruling out continued carriage in known carriers was
      established. Compliance with national guidelines was overseen via site visits at
      healthcare facilities, routine reporting of carrier census and isolation status,
      and the establishment of a network of communications to facilitate reporting on
      identified carriage, contact tracing and screening, and outbreak investigations.
      During the intervention, nosocomial CRE acquisition in acute care declined from a
      monthly high of 55.5 to an annual low of 4.8 cases per 100,000 patient-days (P <
      .001).

PMID- 24304708
TI  - Intima-media thickness of carotid artery and aortic pulse wave velocity as
      determinants of cerebral blood flow velocity.
AB  - The current study aims to check the relationship between parameters derived from
      brachial blood pressure, the carotid artery intima-media thickness (IMT), pulse
      wave velocity (PWV) and mean cerebral blood flow velocity (mCBFV) in the middle
      cerebral artery (MCA). In consecutive adult outpatients we recorded the brachial
      systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure
      (PP), mean arterial blood pressure (MAP), PWV and IMT. mCBFV was assessed using
      Doppler ultrasound probe applied to the transtemporal window. The mean+/-s.d. age
      of 165 patients (50% women) was 56.7+/-11.8 years. Women and men differed
      significantly in SBP, PP, total cholesterol and mCBFV. Age (r=-0.44, P<0.001) and
      BMI (r=-0.25, P<0.01) were significantly and reversely related to mCBFV. Compared
      with healthy individuals, hypertensive (P<0.05) and diabetic (P<0.01) patients
      had lower mCBFV. IMT and PWV were related to mCBFV (IMT, r=-0.36; P<0.001, and
      PWV, r=-0.34; P<0.001). After adjustment for possible confounders, the
      relationship between mCBFV and PWV did not retain statistical significance
      (P=0.54). However, the relationship between mCBFV and IMT remained statistically
      significant (P=0.02). The association between lower CBFV and higher IMT may
      constitute a link between increased IMT and risk of cerebrovascular events. 

PMID- 24304710
TI  - Amplatzer septal occluder migration into the pulmonary trunk: surgical removal
      through a totally thoracoscopic approach.
AB  - The Amplatzer Septal Occluder for transcatheter closure of interatrial
      communications is a standard procedure and a widely accepted alternative to
      surgery in most patients with atrial septal defect (ASD). Device dislocation or
      embolization has been reported as one of the commonest complications of ASD
      percutaneous closure. In this case, if a transcatheter removal is not possible,
      it requires a surgical therapy, usually through a median sternotomy. We report on
      a case of a 30-year-old woman, who underwent percutaneous closure of an ostium
      secundum ASD. After a late embolization of the Amplatzer Septal Occluder into the
      pulmonary trunk 10 months later, the implant was successfully obtained via a
      surgical removal through a video-guided minimally invasive port-access approach.
      This case shows that, in experienced hands, the port-access technique for
      surgical procedures on the pulmonary trunk is feasible, and therefore, it might
      be a good alternative option to the traditional surgery, mainly in young
      patients. 

PMID- 24304709
TI  - Hypovitaminosis D and nocturnal hypertension in obese children: an interesting
      link.
AB  - In adults, low levels of vitamin D are associated with hypertension. The aim of
      this study was to evaluate the relationship between 24-h blood pressure (BP)
      patterns and vitamin D levels in obese children. We recorded anthropometric
      parameters, took blood samples for 25-hydroxivitamin D measurements and monitored
      ambulatory BP (ABP) in 32 obese children (male/female: 21/11, age 7-16 years).
      Subjects in the lower tertiles had higher homeostasis model assessment of insulin
      resistance, nighttime systolic and diastolic ABP, nighttime systolic and
      diastolic ABP load, 24-h ABP index and nighttime systolic and diastolic ABP index
      than those in the higher tertile. Vitamin D correlated negatively with 24-h and
      nighttime systolic ABP, 24-h systolic ABP load, nighttime systolic and diastolic
      ABP load, 24-h systolic ABP index and nighttime systolic ABP index. The
      percentage of subjects with pathological 24-h systolic BP (SBP) load, nighttime
      SBP load, nighttime diastolic BP (DBP) load, nighttime SBP index and nighttime
      DBP index increased progressively as the vitamin deficiency categories increased
      (chi(2)=10.26, P<0.05; chi(2)=16.34, P<0.01; chi(2)=10.23, P<0.05; chi(2)=10.38
      and chi(2)=10.06, P <0.01). Low levels of vitamin D in obese children were
      associated with a higher BP burden, especially at night. 

PMID- 24304711
TI  - Images in Anesthesiology: near-complete upper airway obstruction from a grape.

PMID- 24304713
TI  - On being a doll.

PMID- 24304712
TI  - Reducing tobacco-related cancer incidence and mortality: summary of an institute
      of medicine workshop.
AB  - Tobacco use remains a serious and persistent national problem. Recognizing that
      progress in combating cancer will never be fully achieved without addressing the
      tobacco problem, the National Cancer Policy Forum of the Institute of Medicine
      convened a public workshop exploring current issues in tobacco control, tobacco
      cessation, and implications for cancer patients. Workshop participants discussed
      potential policy, outreach, and treatment strategies to reduce tobacco-related
      cancer incidence and mortality, and highlighted a number of potential high-value
      action items to improve tobacco control policy, research, and advocacy. 

PMID- 24304714
TI  - Lasing from individual GaAs-AlGaAs core-shell nanowires up to room temperature.
AB  - Semiconductor nanowires are widely considered to be the next frontier in the
      drive towards ultra-small, highly efficient coherent light sources. While NW
      lasers in the visible and ultraviolet have been widely demonstrated, the major
      role of surface and Auger recombination has hindered their development in the
      near infrared. Here we report infrared lasing up to room temperature from
      individual core-shell GaAs-AlGaAs nanowires. When subject to pulsed optical
      excitation, NWs exhibit lasing, characterized by single-mode emission at 10 K
      with a linewidth <60 GHz. The major role of non-radiative surface recombination
      is obviated by the presence of an AlGaAs shell around the GaAs-active region.
      Remarkably low threshold pump power densities down to ~760 W cm(-2) are observed
      at 10 K, with a characteristic temperature of T(0)=109+/-12 K and lasing
      operation up to room temperature. Our results show that, by carefully designing
      the materials composition profile, high-performance infrared NW lasers can be
      realised using III/V semiconductors.

PMID- 24304715
TI  - "lauft."--a school-based multi-component program to establish a physically active
      lifestyle in adolescence: study protocol for a cluster-randomized controlled
      trial.
AB  - BACKGROUND: Physical activity during childhood and adolescence is associated with
      substantial health benefits and tracks into adulthood. Nevertheless, only 22.7%
      of German adolescents are sufficiently physically active. Thus, the promotion of
      an active lifestyle in youth is an essential issue of public health.This study
      will evaluate the implementation and efficacy of the "lauft." program to enhance
      physical activity in adolescence. "lauft." is a multicomponent school-based
      program developed on the basis of effective strategies for health interventions
      and behavioral change. METHODS/DESIGN: The "lauft." physical activity program
      targets four different levels. (a) Each student receives a pedometer and
      documents his/her steps over 12 weeks using an interactive user account on the
      "lauft." homepage. (b) For classes there will be different competitions, with
      achieving the most steps in selected weeks, the highest increases of steps and
      developing the most inventive ideas to promote physical activity in school.
      Besides, the intervention includes four educational lessons. (c) The headmasters
      and teaching staff of the participating schools will get information material
      with suggestions and encouragement to enhance physical activity in school.
      Participating teachers will be invited to an introductory seminar. (d) Parents
      will be provided with informational material about the program and will be
      invited to a parent-teacher conference about the benefits of being physically
      active and how they can support their children in engaging in a physically active
      lifestyle.To evaluate the efficacy of the "lauft." physical activity program, a
      two-arm cluster randomized controlled trial will be conducted in three waves: (1)
      baseline assessment, January/February 2014, (2) post assessment, June/July 2014
      and (3) 12-month follow-up assessment, June/July 2015. Data collection will
      include physical and medical testing, self-administered questionnaires, group
      discussions and document analyses. DISCUSSION: "lauft." aims at fostering a
      physically active lifestyle in adolescence while a considerable decline of
      physical activity is present. Physical activity programs based in the school
      setting and following a multicomponent approach have been proven to be most
      successful. Furthermore, the use of pedometers is promising to enhance physical
      activity during the entire day and targets a wide range of adolescents regarding
      fitness and weight. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49482118.

PMID- 24304717
TI  - Motor skills training promotes motor functional recovery and induces
      synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in
      rats.
AB  - We investigated the effects of motor skills training on several types of motor
      function and synaptic plasticity following intracerebral hemorrhage (ICH) in
      rats. Male Wistar rats were injected with collagenase into the left striatum to
      induce ICH, and they were randomly assigned to the ICH or sham groups. Each group
      was divided into the motor skills training (acrobatic training) and control (no
      exercise) groups. The acrobatic group performed acrobatic training from 4 to 28
      days after surgery. Motor functions were assessed by motor deficit score, the
      horizontal ladder test and the wide or narrow beam walking test at several time
      points after ICH. The number of DeltaFosB-positive cells was counted using
      immunohistochemistry to examine neuronal activation, and the PSD95 protein levels
      were analyzed by Western blotting to examine synaptic plasticity in the bilateral
      sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills
      training following ICH significantly improved gross motor function in the early
      phase after ICH and skilled motor coordinated function in the late phase. The
      number of DeltaFosB-positive cells in the contralateral sensorimotor cortex in
      the acrobatic group significantly increased compared to the control group. PSD95
      protein expression in the motor cortex significantly increased in the late phase,
      and in the striatum, the protein level significantly increased in the early phase
      by motor skills training after ICH compared to no training after ICH. We
      demonstrated that motor skills training improved motor function after ICH in rats
      and enhanced the neural activity and synaptic plasticity in the striatum and
      sensorimotor cortex. 

PMID- 24304716
TI  - Comparative genomics of transport proteins in developmental bacteria: Myxococcus
      xanthus and Streptomyces coelicolor.
AB  - BACKGROUND: Two of the largest fully sequenced prokaryotic genomes are those of
      the actinobacterium, Streptomyces coelicolor (Sco), and the delta
      proteobacterium, Myxococcus xanthus (Mxa), both differentiating, sporulating,
      antibiotic producing, soil microbes. Although the genomes of Sco and Mxa are the
      same size (~9 Mbp), Sco has 10% more genes that are on average 10% smaller than
      those in Mxa. RESULTS: Surprisingly, Sco has 93% more identifiable transport
      proteins than Mxa. This is because Sco has amplified several specific types of
      its transport protein genes, while Mxa has done so to a much lesser extent.
      Amplification is substrate- and family-specific. For example, Sco but not Mxa has
      amplified its voltage-gated ion channels but not its aquaporins and mechano
      sensitive channels. Sco but not Mxa has also amplified drug efflux pumps of the
      DHA2 Family of the Major Facilitator Superfamily (MFS) (49 versus 6), amino acid
      transporters of the APC Family (17 versus 2), ABC-type sugar transport proteins
      (85 versus 6), and organic anion transporters of several families. Sco has not
      amplified most other types of transporters. Mxa has selectively amplified one
      family of macrolid exporters relative to Sco (16 versus 1), consistent with the
      observation that Mxa makes more macrolids than does Sco. CONCLUSIONS: Except for
      electron transport carriers, there is a poor correlation between the types of
      transporters found in these two organisms, suggesting that their solutions to
      differentiative and metabolic needs evolved independently. A number of unexpected
      and surprising observations are presented, and predictions are made regarding the
      physiological functions of recognizable transporters as well as the existence of
      yet to be discovered transport systems in these two important model organisms and
      their relatives. The results provide insight into the evolutionary processes by
      which two dissimilar prokaryotes evolved complexity, particularly through
      selective chromosomal gene amplification.

PMID- 24304718
TI  - Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as
      determined by heart rate responses in mice.
AB  - Heterozygous (HZ) missense mutations in the gene encoding syntaxin binding
      protein 1 (Stxbp1 or Munc18-1), a presynaptic protein essential for
      neurotransmitter release, causes early infantile epileptic encephalopathy,
      abnormal brain structure and mental retardation in humans. Here we investigated
      whether the mouse model mimics symptoms of the human phenotype. The effects of
      the deletion of munc18-1 were studied in HZ and wild-type (WT) mice based on
      heart rate (HR) and its variability (HRV) as independent measures to expand
      previous behavioral results of enhanced anxiety and impaired emotional learning
      suggesting mild cognitive impairments. HR responses were assessed during novelty
      exposure, during the expression and extinction of conditioned tone-dependent fear
      and during the diurnal phase. Novelty exposure yielded no differences in activity
      patterns between the two genotypes, while maximum HR differed significantly (WT:
      770 bpm; HZ: 790 bpm). Retention tests after both auditory delay and trace fear
      conditioning showed a delayed extinction of the conditioned HR response in HZ
      mice compared to WT mice. Since the HR versus HRV correlation and HR dynamics
      assessed by nonlinear methods revealed similar function in HZ and WT mice, the
      higher HR responses of munc18-1 HZ mice to different emotional challenges cannot
      be attributed to differences in autonomic nervous system function. Thus, in
      contrast to the adverse consequences of deletion of a single allele of munc18-1
      in humans, C57BL/6J mice show enhanced anxiety responses based on HR adjustments
      that extend previous results on the behavioral level without support of cognitive
      impairment, epileptic seizures and autonomic dysregulation.

PMID- 24304719
TI  - Lack of dopamine D4 receptor affinity contributes to the procognitive effect of
      lurasidone.
AB  - We previously demonstrated among several antipsychotics exhibiting potent
      dopamine D2 receptor antagonism that only lurasidone, (1R,2S,3R,4S)-N-[(1R,2R)-2
      [4-(1,2-benzisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3
      bicyclo[2.2.1] heptanedicarboximide hydrochloride, improved performance in the
      object retrieval detour (ORD) task by marmosets. The mechanisms by which only
      lurasidone causes enhancements in cognitive function have not yet been
      established; however, most antipsychotics, except for lurasidone, have been shown
      to exhibit potent antagonistic activity against the dopamine D4 receptor. The
      objectives of this study were to evaluate the role of the dopamine D4 receptor on
      executive function with the selective agonist, Ro10-5824 and antagonist, L
      745,870, and elucidate a possible mechanism for the procognitive effect of
      lurasidone. The effects of these drugs were evaluated in naive marmosets using
      the ORD task. Changes in the success rate during the difficult trial in the task
      were used to assess the cognitive effect of the drugs. Ro10-5824 (0.3-3 mg/kg)
      increased the success rate in the difficult trial, potentiated the effect of
      lurasidone, and reversed the cognitive impairment induced by clozapine.
      Interestingly, the co-administration of L-745,870 with lurasidone decreased the
      success rate in the difficult trial, whereas the single administration of L
      745,870 had no effect. These results suggest that activation of the dopamine D4
      receptor may improve executive function, whereas concomitant blockade of dopamine
      D4 and D2 receptors may have the opposite effect. In addition to the other unique
      binding profiles of other monoamine receptors, the lack of affinity for the
      dopamine D4 receptor by lurasidone could also contribute, at least partly, to its
      cognitive-enhancing effect.

PMID- 24304720
TI  - Postnatal maternal separation enhances tonic GABA current of cortical layer 5
      pyramidal neurons in juvenile rats and promotes genesis of GABAergic neurons in
      neocortical molecular layer and subventricular zone in adult rats.
AB  - Postnatal maternal separation (PMS) has been shown to be associated with an
      increased vulnerability to psychiatric illnesses in adulthood. However, the
      underlying neurological mechanisms are not well understood. Here we evaluated its
      effects on neurogenesis and tonic GABA currents of cortical layer 5 (L5)
      pyramidal neurons. PMS not only increased cell proliferation in the
      subventricular zone, cortical layer 1 and hippocampal dentate gyrus in the adult
      brain, but also promoted the newly generated cells to differentiate into
      GABAergic neurons, and PMS adult brain maintained higher ratios of GABAergic
      neurons in the survival of newly generated cells within 5 days immediately post
      PMS. Additionally, PMS increased the tonic currents at P7-10 and P30-35 in
      cortical L5 pyramidal cells. Our results suggest that the newly generated
      GABAergic neurons and the low GABA concentration-activated tonic currents may be
      involved in the development of psychiatric disorders after PMS. 

PMID- 24304722
TI  - Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability
      in cancer cell lines.
AB  - Metastatic outcome is impacted by the biophysical state of the primary tumor
      cell. To determine if changes in cancer cell biophysical properties facilitate
      metastasis, we quantified cytoskeletal biophysics in well-characterized human
      skin, bladder, prostate and kidney cell line pairs that differ in metastatic
      ability. Using magnetic twisting cytometry with optical detection, cytoskeletal
      dynamics was observed through spontaneous motion of surface bound marker beads
      and nonlinear rheology was characterized through large amplitude forced
      oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear
      rheology differed between strongly and weakly metastatic cells. However, no set
      of biophysical parameters changed systematically with metastatic ability across
      all cell lines. Compared to their weakly metastatic counterparts, the strongly
      metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and
      stiffness at large deformation which are thought to facilitate the process of
      vascular invasion. 

PMID- 24304723
TI  - Inter-organ communication in the regulation of lipid metabolism: focusing on the
      network between the liver, intestine, and heart.
AB  - Recent studies have shown that lipid metabolism is regulated through the
      orchestration of multiple organs. Gut microbiota influences the metabolism of the
      liver through the production of fatty acids and phosphatidylcholine as well as
      the modulation of bile acid profile. Microbiota also affects the cardiovascular
      system through the production of metabolites from nutrients. MicroRNAs (miRNAs)
      are non-coding RNAs comprised of around 22 nucleotides in length. MiRNAs are
      released into blood flow from organs and interfere with the gene expression of
      target organs. MiRNAs are involved in the regulation of metabolic homeostasis
      including lipoprotein production and cardiovascular functions. Fatty acids are
      also circulating and distributed to each organ by fatty acid transporting
      proteins. Fatty acids can act as a ligand of G protein-coupled receptors, such as
      GPR41 and GPR43, and nuclear receptor PPARalpha, which bear crucial roles in the
      regulation of energy expenditure. Therefore the inter-organ communication plays
      important roles in the systematic regulation of lipid metabolism. Studies on the
      inter-organ network system will contribute to the development of diagnostic and
      therapeutic strategies for metabolic diseases. This review discusses how lipid
      metabolism is regulated by the inter-organ communication, focusing on the network
      axis between the liver, intestine, and heart. 

PMID- 24304721
TI  - Phosphatidylinositol 3-Kinase dependent upregulation of the epidermal growth
      factor receptor upon Flotillin-1 depletion in breast cancer cells.
AB  - BACKGROUND: Flotillin-1 and flotillin-2 are two homologous and ubiquitously
      expressed proteins that are involved in signal transduction and membrane
      trafficking. Recent studies have reported that flotillins promote breast cancer
      progression, thus making them interesting targets for breast cancer treatment. In
      the present study, we have investigated the underlying molecular mechanisms of
      flotillins in breast cancer. METHODS: Human adenocarcinoma MCF7 breast cancer
      cells were stably depleted of flotillins by means of lentivirus mediated short
      hairpin RNAs. Western blotting, immunofluorescence and quantitative real-time PCR
      were used to analyze the expression of proteins of the epidermal growth factor
      receptor (EGFR) family. Western blotting was used to investigate the effect of
      EGFR stimulation or inhibition as well as phosphatidylinositol 3-kinase (PI3K)
      inhibition on mitogen activated protein kinase (MAPK) signaling. Rescue
      experiments were performed by stable transfection of RNA intereference resistant
      flotillin proteins. RESULTS: We here show that stable knockdown of flotillin-1 in
      MCF7 cells resulted in upregulation of EGFR mRNA and protein expression and
      hyperactivation of MAPK signaling, whereas ErbB2 and ErbB3 expression were not
      affected. Treatment of the flotillin knockdown cells with an EGFR inhibitor
      reduced the MAPK signaling, demonstrating that the increased EGFR expression and
      activity is the cause of the increased signaling. Stable ectopic expression of
      flotillins in the knockdown cells reduced the increased EGFR expression,
      demonstrating a direct causal relationship between flotillin-1 expression and
      EGFR amount. Furthermore, the upregulation of EGFR was dependent on the PI3K
      signaling pathway which is constitutively active in MCF7 cells, and PI3K
      inhibition resulted in reduced EGFR expression. CONCLUSIONS: This study
      demonstrates that flotillins may not be suitable as cancer therapy targets in
      cells that carry certain other oncogenic mutations such as PI3K activating
      mutations, as unexpected effects are prone to emerge upon flotillin knockdown
      which may even facilitate cancer cell growth and proliferation.

PMID- 24304724
TI  - Pathologic complete response after preoperative anti-HER2 therapy correlates with
      alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling.
AB  - BACKGROUND: To define protein molecular characteristics of tumor cells prior to,
      and immediately following, preoperative human epidermal growth factor receptor 2
      (HER2)-targeted therapy that correlate with pathologic complete response (pCR) or
      non response (no pCR) to preoperative HER2-directed therapy and chemotherapy.
      METHODS: This open-label, phase II study randomized patients with HER2-positive
      stage II or III invasive breast cancer to trastuzumab, lapatinib, or both, 2
      weeks prior to and during chemotherapy with FEC75 for 4 courses; then paclitaxel
      80 mg/m2 weekly for 12 courses, then surgery. Core needle biopsies were collected
      at baseline and after 2 weeks of anti-HER2 therapy prior to chemotherapy. Data
      were correlated with pCR, defined as absence of invasive tumor in breast and
      lymph nodes. RESULTS: Of 100 enrolled patients, the analysis population included
      those who had surgery and received >=75% chemotherapy (78% [n=78]). pCRs by arm
      are: trastuzumab (n=26), 54% [n=14]; lapatinib (n=29), 45% [n=13]; trastuzumab
      plus lapatinib (n=23), 74% [n=17]). Paired biopsy specimens were available for 49
      patients (63%). Tumor cells of patients with pCR in the trastuzumab or lapatinib
      treatment arms showed nonphosphorylated FOXO, phosphorylated Stat5, and sparse
      signal-transduction protein network crosstalk representing different patterns of
      connections with PI3K and autophagy proteins compared with no pCR. CONCLUSION: In
      this exploratory study, pCR with preoperative anti-HER2 therapy and chemotherapy
      correlated with the levels and phosphorylation status of specific baseline signal
      pathway proteins in tumor cells. These data may provide candidate biomarkers to
      stratify initial treatment and potential combination therapies for future study.
      Tissue preservation technology introduced here makes this procedure widely
      feasible. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00524303.

PMID- 24304725
TI  - General relationships between consumer dispersal, resource dispersal and
      metacommunity diversity.
AB  - One of the central questions of metacommunity theory is how dispersal of
      organisms affects species diversity. Here, we show that the diversity-dispersal
      relationship should not be studied in isolation of other abiotic and biotic flows
      in the metacommunity. We study a mechanistic metacommunity model in which
      consumer species compete for an abiotic or biotic resource. We consider both
      consumer species specialised to a habitat patch, and generalist species capable
      of using the resource throughout the metacommunity. We present analytical results
      for different limiting values of consumer dispersal and resource dispersal, and
      complement these results with simulations for intermediate dispersal values. Our
      analysis reveals generic patterns for the combined effects of consumer and
      resource dispersal on the metacommunity diversity of consumer species, and shows
      that hump-shaped relationships between local diversity and dispersal are not
      universal. Diversity-dispersal relationships can also be monotonically increasing
      or multimodal. Our work is a new step towards a general theory of metacommunity
      diversity integrating dispersal at multiple trophic levels. 

PMID- 24304727
TI  - [Living medicine: Emergency 1986].

PMID- 24304726
TI  - Clinical, economic, and humanistic burden of asthma in Canada: a systematic
      review.
AB  - BACKGROUND: Asthma, one of the most common chronic respiratory diseases, affects
      about 3 million Canadians. The objective of this study is to provide a
      comprehensive evaluation of the published literature that reports on the
      clinical, economic, and humanistic burden of asthma in Canada. METHODS: A search
      of the PubMed, EMBASE, and EMCare databases was conducted to identify original
      research published between 2000 and 2011 on the burden of asthma in Canada.
      Controlled vocabulary with "asthma" as the main search concept was used. Searches
      were limited to articles written in English, involving human subjects and
      restricted to Canada. Articles were selected for inclusion based on predefined
      criteria like appropriate study design, disease state, and outcome measures. Key
      data elements, including year and type of research, number of study subjects,
      characteristics of study population, outcomes evaluated, results, and overall
      conclusions of the study, were abstracted and tabulated. RESULTS: Thirty-three of
      the 570 articles identified by the clinical and economic burden literature
      searches and 14 of the 309 articles identified by the humanistic burden
      literature searches met the requirements for inclusion in this review. The
      included studies highlighted the significant clinical burden of asthma and show
      high rates of healthcare resource utilization among asthma patients
      (hospitalizations, ED, physician visits, and prescription medication use). The
      economic burden is also high, with direct costs ranging from an average annual
      cost of $366 to $647 per patient and a total annual population-level cost ranging
      from ~ $46 million in British Columbia to ~ $141 million in Ontario. Indirect
      costs due to time loss from work, productivity loss, and functional impairment
      increase the overall burden. Although there is limited research on the humanistic
      burden of asthma, studies show a high (31%-50%) prevalence of psychological
      distress and diminished QoL among asthma patients relative to subjects without
      asthma. CONCLUSIONS: As new therapies for asthma become available, economic
      evaluations and assessment of clinical and humanistic burden will become
      increasingly important. This report provides a comprehensive resource for health
      technology assessment that will assist decision making on asthma treatment
      selection and management guidelines in Canada.

PMID- 24304728
TI  - [Flu symptoms and preventive measures practiced by the inhabitants of Mexico City
      during the AH1N1 influenza epidemic].
AB  - OBJECTIVE: To know the frequency of flu symptoms and describe preventive measures
      practiced by the inhabitants of Mexico City during the AH1N1 epidemic. MATERIAL
      AND METHODS: A cross-sectional design was used and a survey containing
      demographic and health information was conducted in August and September 2009 in
      a sample of 4003 randomly selected people living in Mexico City. RESULTS:
      Referred flu symptoms were: 29% running nose, 25% cough, 25% throat infection,
      17% muscle and joint pain, 10% respiratory problems, and 7% fever. Also 16% said
      having hypertension, 10% diabetes, and 2% morbid obesity. Among the preventive
      measures, 74% washed hands, 32% covered the nose and mouth with the forearm when
      coughing or sneezing, 28% used sanitizer gel five times a day in average, and 47%
      did not greet with a kiss or handshake. CONCLUSIONS: Almost all the population
      followed preventive measures and did not show high percentages of influenza
      symptoms. Useful elements for prevention were identified, such as the frequency
      of seasonal influenza vaccination, self-medication, and living with a person
      diagnosed with AH1N1. It is important to continue with mass communication to
      strengthen adequate hygiene and health measures.

PMID- 24304729
TI  - Nutritional care, time period since diagnosis, demographics and body mass index
      in HIV/AIDS patients.
AB  - BACKGROUND: Nutritional status and nutritional care have long been ignored among
      HIV/AIDS patients. Furthermore, in Mexico there is no information on potential
      factors favoring weight increase in such population. OBJECTIVE: To assess the
      association between the time period since diagnosis, demographics and BMI in
      different categories of patients with HIV/AIDS in Monterrey, Mexico. In addition,
      to provide information on overweight/obesity prevalence and nutritional care
      referral. MATERIAL AND METHODS: This was a cross-sectional study of HIV/AIDS
      positive patients receiving outpatient secondary care (n = 231). Nutritional care
      referral, time period since diagnosis and demographic data were obtained by
      interview. A standardized and registered dietitian collected anthropometrics
      measures. Binary multiple logistic regression was used to evaluate the
      association between increasing BMI categories and variables of interest. RESULTS:
      Mean patient age was 40.6 +/- 11.2 years, 87% were male, 79.2% were economically
      active, 65% were single and 60% had less than a college education. The average
      time since diagnosis was 6.5 +/- 5.4 years. Overweight and obesity prevalence
      were 35.8% and 12.5%, respectively. Only 18% of patients had ever been referred
      for nutritional care. The time period since diagnosis, the sum of skinfold
      measurements and the waist-to-hip ratio, were significantly predictive of the BMI
      category (normal/underweight vs. overweight/obese), when controlling for
      nutritional care referral and daily carbohydrate intake; age and marital status
      were not associated with BMI category. CONCLUSIONS: Identification of
      predisposing factors to overweight/obesity among HIV/AIDS patients constitutes a
      significant step for providing nutritional care, of the same importance as the
      load or CD4+ count, especially nowadays, with more common increased survival
      rates and consequently, longer lives with the disease.

PMID- 24304730
TI  - Amniotic band sequence: prenatal diagnosis, phenotype descriptions, and a
      proposal of a new classification based on morphologic findings.
AB  - OBJECTIVE: The aim of this study is to describe the phenotype of fetuses affected
      by amniotic band sequence (ABS) that were diagnosed at the Instituto Nacional de
      Perinatologia Isidro Espinosa de los Reyes and to propose a new classification
      based on morphologic findings. MATERIAL AND METHODS: Cases with a final diagnosis
      of amniotic band sequence, diagnosed between January 1993 and July 2010 in the
      Department of Maternal Fetal Medicine, were reviewed. Demographic, clinical, and
      periconceptional data were collected, and the defects were described and
      classified. The association frequencies of the defects were also determined.
      RESULTS: We included 50 cases with prenatal diagnosis of amniotic band sequence.
      The mean maternal age was 25.7 +/- 6.9 years. Of these patients, 54% (27/50) were
      primiparous compared to 22% (11/50) who had three or more previous pregnancies.
      Craniofacial defects were seen in 78% (39/50) of the cases, followed by defects
      of the extremities 70% (35/50), abdominal wall, spine, and/or thorax 52% (26/50).
      The most frequent defects were the following: a) Encephalocele and facial clefts
      in the craniofacial group. b) Shortening at any level in the limb defects group,
      and c) Alterations of the spinal column curvature in the group of "other"
      defects. CONCLUSIONS: The amniotic band sequence shows a tendency to affect women
      who are in their earlier years of reproduction. We observed an inverse
      relationship between the number of pregnancies and the frequency of presentation
      of this pathology. The majority of affected fetuses showed a phenotype that fit
      into one of many groups. Therefore, we propose classifying the amniotic band
      sequence phenotypes into the following groups: I. Craniofacial defect + limb
      defect. II. Craniofacial defect + limb defect + abdominal wall, spinal column,
      and/or thoracic defects. III. Limb defect + abdominal wall, spinal column, and/or
      thoracic defects; and IV. Isolated defect (craniofacial, limb, or thoraco
      abdominal wall). This classification system will be helpful in diagnosing
      amniotic band sequence. Based on future research studies, we hope that we can use
      this classification system as a prognosis fetal factor to establish a more
      accurate fetal prognosis and recurrence probability. Finally, we created a
      flowchart describing all of the steps that were followed by our Department from
      the moment an amniotic band was found by ultrasound until the definitive
      diagnosis was made and the follow up according to the fetal findings.

PMID- 24304731
TI  - [Decrease of liver fat content by aerobic exercise or metformin therapy in
      overweight or obese women].
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is characterized by high
      intrahepatic triglyceride level. It is associated with an increased prevalence of
      cardiovascular disease, independently of underlying cardiometabolic risk factors.
      Metformin is used as a pharmacological treatment; the adherence is low because of
      the presence of adverse effects. Aerobic exercise could be an alternative
      therapy, but its effectiveness compared with metformin has not been established
      in the treatment of NAFLD. The aim of this study was to establish the
      effectiveness of aerobic exercise and its influence in reducing cardiovascular
      risk in overweight or obese women with NAFLD. MATERIAL AND METHODS: Sedentary
      women 25-60 years old with body mass index (BMI) > 24.9 kg/m2 and liver fat
      content < 50 HU, were randomly divided into two parallel groups: exercise group
      (EG) or metformin group (MG). The EG performed an aerobic exercise program of 60
      min/5 days/ week at 60-85% of heart rate reserve; the MG took 1 g/day of
      metformin each morning. The duration of the intervention was 12 weeks. The liver
      fat content, metabolic and cardiorespiratory- fitness parameters were evaluated
      at the beginning and end of the program. The study complied with the Helsinki
      ethics codes for human research. RESULTS: The study included a sample of 16
      women, with 8 per group. The treatments modified the liver fat content by 14.6%
      (CI95% 0.92, 28.36) and 10.37% (CI95% -1.74, 22.48) for the EG and MG,
      respectively. In the EG, the insulin levels and HOMA-IR decreased (P < 0.05), and
      the cardiovascular fitness improved. CONCLUSIONS: An aerobic exercise program of
      12 weeks with a volume training of 300 min/week and a moderate to vigorous
      intensity (60-85% VO2peak) modified the liver fat content and improved
      cardiovascular risk factors during the intervention. Exercise contributed to a
      holistic approach by modifying a number of the components of metabolic syndrome,
      cardiorespiratory-fitness, and cardiovascular risk.

PMID- 24304732
TI  - [Surgical treatment of renal-cell carcinoma in von Hippel-Lindau disease].
AB  - OBJECTIVE: To describe the clinical outcome of surgical treatment of renal-cell
      carcinoma in patients with von Hippel-Lindau disease. To analyze the clinical,
      demographic and histopathological characteristics. MATERIAL AND METHODS: From a
      total of 468 patients with renal-cell carcinoma treated surgically at our
      institution from 1982 to 2010, a series of 8 with von Hippel-Lindau disease were
      identified. Relevant variables included tumor recurrence, surgical approach,
      recurrence rate and mid-term preserved renal function. RESULTS: Eight patients
      with von Hippel-Lindau disease and renal cell carcinoma were identified; 7 were
      treated with nephron-sparing surgery and 1 with radical nephrectomy. During the
      follow-up of 89.3 +/- 67.5 months, we found ipsilateral tumor recurrence in two
      patients and contralateral in another one. Mean survival time was 72 months in
      seven out of eight patients who also preserved normal renal function; one patient
      with uncontrolled diabetes died from complications of chronic kidney disease five
      years after surgery. CONCLUSIONS: Nephron-sparing surgery offers acceptable
      oncologic and functional results for patients with renal cell carcinoma and Von
      Hippel-Lindau disease.

PMID- 24304733
TI  - Safety of the oral methionine load test: effects on the clinical performance and
      laboratory tests.
AB  - INTRODUCTION: Hyperhomocysteinemia is a prothrombotic risk factor. Homocysteine
      is evaluated during fasting and after an oral methionine load (OML). AIM: To
      determine the safety of the OML test according to the general performance status
      and clinical laboratory tests. We studied healthy nonsmoking volunteers and
      patients with several thrombotic conditions. Before and after receiving an OML,
      blood samples were obtained to perform several laboratory tests. We also
      evaluated acute and subacute adverse effects and 30-day associated morbidity and
      mortality. Of 353 individuals, three were eliminated because they did not
      tolerate the OML. We studied 175 healthy individuals and 175 patients without age
      differences. After OML, mild to moderate clinical abnormalities were recorded in
      78 subjects (22.1%): nausea (n = 69; 88.5%), dizziness (n = 13; 16.7%) and
      decreased or increased blood pressure (n = 8; 10.2%). Nausea always disappeared
      after breakfast in affected individuals. Prevalence of complications was similar
      in patients and controls. No patient required hospitalization and there was no
      mortality during the 30-day study period. In conclusion, OML test had no
      significant undesirable effects on the clinical status or the general laboratory
      tests of patients and healthy controls. Some mild and moderate symptoms
      associated with OML tests were observed, and OML test did not negatively affect
      general laboratory tests. OML test is a safe diagnostic procedure in patients
      with previous thrombotic events (and with the consequent associated risk factors
      such as diabetes mellitus or dyslipidemia) and in healthy subjects.

PMID- 24304734
TI  - A short-term training program reduced oxidative damage in elderly diabetic rats.
AB  - INTRODUCTION: Recent studies concluded long-term training programs have improved
      antioxidant system in young and adults diabetic rats. However, to our knowledge,
      little attention has been paid to elderly individuals. OBJECTIVE: To assess the
      influence of a shorter training program in reducing oxidative damage in elderly
      diabetic rats. MATERIAL AND METHODS: Twenty-four male homozygous Zucker diabetic
      fatty rats (Gmi, fa/fa) aged 18-weeks with an average weight of 370- 450 g were
      purchased. After a 2-week period of environmental adaptation, animals were
      randomly distributed into exercised group (n = 12) that performed a 6-week
      swimming training protocol and sedentary group (n = 12). Animals were sacrificed
      24-h after the last exercise session under anesthesia. Serum metabolic profile
      was determined. Lipid oxidation, expressed as malondialdehyde and protein
      oxidation, expressed as carbonyl groups, were assessed in plasma samples. This
      protocol was approved by an Institutional Ethics Committee. RESULTS: Exercised
      rats improved significantly their metabolic profile in comparison to controls.
      Plasma malondialdehyde (1.58 +/- 0.39 vs. 2.06 +/- 0.41 nmol/mL; p = 0.016) and
      carbonyl group levels (1.37 +/- 0.33 vs. 1.62 +/- 0.58 UA; p = 0.011) were also
      significantly lowered in exercised rats when compared to sedentary counterparts.
      CONCLUSIONS: A 6-week swimming training program reduced lipid and protein
      oxidation in elderly fatty diabetic rats. Further studies on this topic are
      required.

PMID- 24304735
TI  - [Inhibitory proteins of neuritic regeneration in the extracellular matrix:
      structure, molecular interactions and their functions. Mechanisms of
      extracellular balance].
AB  - After injury of the central nervous system (CNS) in higher vertebrates, neurons
      neither grow nor reconnect with their targets because their axons or dendrites
      cannot regenerate within the injured site. In the CNS, the signal from the
      environment regulating neurite regeneration is not exclusively generated by one
      molecular group. This signal is generated by the interaction of various types of
      molecules such as extracellular matrix proteins, soluble factors and surface
      membrane molecules; all these elements interact with one another generating the
      matrix's biological state: the extracellular balance. Proteins in the balanced
      extracellular matrix, support and promote cellular physiological states,
      including neuritic regeneration. We have reviewed three types of proteins of the
      extracellular matrix possessing an inhibitory effect and that are determinant of
      neuritic regeneration failure in the CNS: chondroitin sulfate proteoglycans,
      keratan sulfate proteoglycans and tenascin. We also review some of the mechanisms
      involved in the balance of extracellular proteins such as isomerization,
      epimerization, sulfation and glycosylation as well as the assemblage of the
      extracellular matrix, the interaction between the matrix and soluble factors and
      its proteolytic degradation. In the final section, we have presented some
      examples of the matrix's role in development and in tumor propagation. 

PMID- 24304736
TI  - [Clinical forum: immunopathology of meningeal tuberculosis].

PMID- 24304737
TI  - AL amyloidosis: an epidemiological and clinical challenge.

PMID- 24304738
TI  - Answer to the letter AL amyloidosis: an epidemiological and clinical challenge.

PMID- 24304739
TI  - [Reflections on the 2012 Nobel Prize in Medicine].

PMID- 24304740
TI  - [Reflections on the 2012 Nobel Prize in Medicine].

PMID- 24304741
TI  - [Reflections on the 2012 Nobel Prize in Medicine. Editor's reply].

PMID- 24304742
TI  - Counterpoint to Dr de Campo's letter.

PMID- 24304743
TI  - Individual and community perceptions of surgical care in Sierra Leone.
AB  - OBJECTIVES: To determine themes and beliefs that influence health-seeking
      behaviour and barriers to accessing surgical care. METHODS: In January 2012 in
      Western Area Province of Sierra Leone, six Focus Group Discussions (FGDs) were
      conducted. The FDGs consisted of three male only and three female only groups in
      an urban, a slum and a rural setting. Researchers investigated a wide range of
      topics including definitions of surgery, types of surgical procedures, trust,
      quality of care, human resources, post-operative care, permission-seeking and
      traditional beliefs. RESULTS: Although many individual beliefs were expressed,
      common fears were as follows: becoming half human after surgery; complications
      from procedures; stigma from having a scar; and financial burdens resulting from
      the cost of care. Participants also expressed concern about the quality of the
      care available in Sierra Leone. CONCLUSIONS: The concept of being half human
      after surgery, previously not documented in the literature, is noteworthy and
      should be explored more fully. Qualitative research in other parts of Sierra
      Leone and other LMICs into beliefs of the local population could improve
      programmes for access and delivery of surgical care.

PMID- 24304744
TI  - Spinal anesthesia with hyperbaric bupivacaine: a comparison of hypertensive and
      normotensive patients.
AB  - BACKGROUND: Hypotension is the most common problem with spinal anesthesia. This
      prospective study aimed to compare normotensive and hypertensive patients with
      respect to the hemodynamic effects of spinal anesthesia performed with hyperbaric
      bupivacaine. MATERIAL AND METHODS: Sixty patients who were scheduled to undergo
      various elective operations under spinal anesthesia were included into the study.
      The patients were separated into 2 groups: hypertensive patients constituted
      Group H (n=30) and normotensive patients constituted Group N (n=30). After fluid
      loading, spinal anesthesia was performed with 3.5 ml 0.5% hyperbaric bupivacaine.
      Demographic characteristics and incidence of hypotension and bradycardia were
      compared. Systolic (SBP), diastolic (DBP), and mean blood pressures (MBP) and
      heart rate (HR) were also compared before and after spinal anesthesia. RESULTS:
      There was no significant difference between the groups with respect to
      demographic characteristics, maximal height of sensory block, incidences of
      hypotension and bradycardia, and the amount of fluids infused (p>0.05). In the
      hypertensive patient group, the SBP, DBP, and MBP values were significantly
      higher than in the normotensive patient group at all measurement times (p<0.05).
      Comparison within the groups did not reveal any significant differences in either
      group compared to the basal values (p>0.05). There were no significant
      differences in HR between or within groups (p>0.05). CONCLUSIONS: There was no
      significant difference between normotensive and hypertensive patients in the
      incidences of hypotension caused by spinal anesthesia with 0.5% hyperbaric
      bupivacaine.

PMID- 24304745
TI  - Working memory training for adult hearing aid users: study protocol for a double
      blind randomized active controlled trial.
AB  - BACKGROUND: One in ten people aged between 55 to 74 years have a significant
      hearing impairment in their better hearing ear (as defined by audiometric hearing
      thresholds). However, it is becoming increasingly clear that the challenges faced
      by older listeners cannot be explained by the audiogram alone. The ability for
      people with hearing loss to use cognition to support speech perception allows for
      compensation of the degraded auditory input. This in turn offers promise for new
      cognitive-based rehabilitative interventions. Working memory is known to be
      highly associated with language comprehension and recent evidence has shown
      significant generalization of learning from trained working memory tasks to
      improvements in sentence-repetition skills of children with severe to profound
      hearing loss. This evidence offers support for further investigation into the
      potential benefits of working memory training to improve speech perception
      abilities in other hearing impaired populations. METHODS/DESIGN: This is a double
      blind randomized active controlled trial aiming to assess whether a program of
      working memory training results in improvements in untrained measures of
      cognition, speech perception and self-reported hearing abilities in adult hearing
      aid users aged (50 to 74 years) with mild-to-moderate hearing loss hearing aid
      users, compared with an active control group who receive a placebo version of the
      working memory training program. DISCUSSION: The present study aims to generate
      high-quality preliminary evidence for the efficacy of working memory training for
      adult hearing aid users with mild-to-moderate sensorineural hearing loss who are
      existing hearing aid users. This trial addresses a number of gaps in the
      published literature assessing training interventions for people with hearing
      loss, and in the general literature surrounding working memory training, such as
      the inclusion of an active control group, participant and tester blinding, and
      increased transparency in reporting. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT01892007. Date of registration: 27 June 2013.

PMID- 24304746
TI  - Such stuff as dreams are made on? Elaborative encoding, the ancient art of
      memory, and the hippocampus.
AB  - This article argues that rapid eye movement (REM) dreaming is elaborative
      encoding for episodic memories. Elaborative encoding in REM can, at least
      partially, be understood through ancient art of memory (AAOM) principles:
      visualization, bizarre association, organization, narration, embodiment, and
      location. These principles render recent memories more distinctive through novel
      and meaningful association with emotionally salient, remote memories. The AAOM
      optimizes memory performance, suggesting that its principles may predict aspects
      of how episodic memory is configured in the brain. Integration and segregation
      are fundamental organizing principles in the cerebral cortex. Episodic memory
      networks interconnect profusely within the cortex, creating omnidirectional
      "landmark" junctions. Memories may be integrated at junctions but segregated
      along connecting network paths that meet at junctions. Episodic junctions may be
      instantiated during non-rapid eye movement (NREM) sleep after hippocampal
      associational function during REM dreams. Hippocampal association involves
      relating, binding, and integrating episodic memories into a mnemonic
      compositional whole. This often bizarre, composite image has not been present to
      the senses; it is not "real" because it hyperassociates several memories. During
      REM sleep, on the phenomenological level, this composite image is experienced as
      a dream scene. A dream scene may be instantiated as omnidirectional neocortical
      junction and retained by the hippocampus as an index. On episodic memory
      retrieval, an external stimulus (or an internal representation) is matched by the
      hippocampus against its indices. One or more indices then reference the relevant
      neocortical junctions from which episodic memories can be retrieved. Episodic
      junctions reach a processing (rather than conscious) level during normal wake to
      enable retrieval. If this hypothesis is correct, the stuff of dreams is the stuff
      of memory.

PMID- 24304747
TI  - The analogy between dreams and the ancient art of memory is tempting but
      superficial.
AB  - Although the analogy between dreams and ancient mnemotechniques is tempting
      because they share several phenomenological characteristics, this analogy is
      superficial at a closer look. Unlike mneomotechnically encoded material, rapid
      eye movement (REM) dreams are inherently difficult to remember, do not usually
      allow conscious subsequent retrieval of all interconnected elements, and have
      been found to support subsequent episodic memory in only rare cases. 

PMID- 24304748
TI  - Some Renaissance, Baroque, and contemporary cultural elaborations of the art of
      memory.
AB  - The target article addresses historical and present-day mnemotechnics as a
      practice. It also deserves scrutiny as culture writ small. For would-be Hermetic
      adepts of the Renaissance and Baroque, the ancient art of memory (AAOM) provided
      both an iconography and a projective-test vision of possibilities. In
      contemporary fiction, Memory Palaces become a metaphor for the workings of mind,
      of culture, and of information technology.

PMID- 24304749
TI  - Dreams are made of memories, but maybe not for memory.
AB  - Llewellyn's claim that rapid eye movement (REM) dream imagery may be related to
      the processes involved in memory consolidation during sleep is plausible.
      However, whereas there is voluntary and deliberate intention behind the
      construction of images in the ancient art of memory (AAOM) method, there is a
      lack of intentionality in producing dream images. The memory for dreams is also
      fragile, and dependent on encoding once awake.

PMID- 24304750
TI  - Composition and replay of mnemonic sequences: the contributions of REM and slow
      wave sleep to episodic memory.
AB  - We propose that rapid eye movement (REM) and slow-wave sleep contribute
      differently to the formation of episodic memories. REM sleep is important for
      building up invariant object representations that eventually recur to gamma-band
      oscillations in the neocortex. In contrast, slow-wave sleep is more directly
      involved in the consolidation of episodic memories through replay of sequential
      neural activity in hippocampal place cells. 

PMID- 24304751
TI  - Such stuff as NREM dreams are made on?
AB  - The question that we deal with in this commentary is the need to clarify the
      synergistic role of different non-rapid eye movement (NREM) sleep stages (stages
      2 and 3-4) with REM and while awake in elaborative encoding of episodic memory.
      If the assumption is that there is isomorphism between neuronal and cognitive
      networks, then more detailed analysis of NREM sleep and dreams is absolutely
      necessary. 

PMID- 24304752
TI  - Such stuff as psychoses are made on?
AB  - In her target article, Sue Llewellyn concludes that an unconstrained form of
      consciousness is necessary for the elaboration of meaningful associations. Unlike
      the author's view that dedifferentiation of memory encoding processes across
      wakefulness and sleep determines schizophrenia, our proposal suggests this
      mechanism could reflect a common neurobiological substrate for psychosis across
      several different diagnostic domains. 

PMID- 24304753
TI  - Don't count your chickens before they're hatched: elaborative encoding in REM
      dreaming in face of the physiology of sleep stages.
AB  - Llewellyn suggests that episodic memories undergo "elaborative encoding" during
      rapid eye movement (REM) dreams, generating novel associations between recent and
      remote memories that are then instantiated during non-REM (NREM) sleep. This
      hypothesis conflicts with our knowledge of the physiology of NREM and then REM
      sleep stages and their ordered succession. Moreover, associations during sleep
      might also involve the extraction of hidden patterns rather than de novo
      associations. 

PMID- 24304754
TI  - Dream and emotion regulation: insight from the ancient art of memory.
AB  - During dreaming, as well as during wakefulness, elaborative encoding, indexing
      and ancient art of memory (AAOM) techniques, such as the method of loci, may
      coincide with emotion regulation. These techniques shed light on the link between
      dreaming and emotional catharsis, post-traumatic stress disorder,
      supermemorization during sleep as opposed to wakefulness, and the developmental
      role of rapid eye movement (REM) sleep in children. 

PMID- 24304755
TI  - "They who dream by day": parallels between Openness to Experience and dreaming.
AB  - Individuals high in the personality trait Openness to Experience appear to engage
      spontaneously (during wake) in processes of elaborative encoding similar to those
      Llewellyn identifies in both dreaming and the ancient art of memory (AAOM). Links
      between Openness and dreaming support the hypothesis that dreaming is part of a
      larger process of cognitive exploration that facilitates adaptation to new
      experiences. 

PMID- 24304756
TI  - A hippocampal indexing model of memory retrieval based on state trajectory
      reconstruction.
AB  - A method is proposed where static patterns or snapshots of cortical activity that
      could be stored as hyperassociative indices in hippocampus can subsequently be
      retrieved and reinjected into the neocortex in order to enable neocortex to then
      proceed to unfold the corresponding sequence, thus implementing an index-based
      sequence memory storage and retrieval capability. 

PMID- 24304757
TI  - Mnemonic expertise during wakefulness and sleep.
AB  - We studied the world's most distinguished experts in the use of mnemonic
      techniques: the top participants of the World Memory Championships. They neither
      feel the use of mnemonics to be dreamlike, nor does their REM sleep differ from
      mnemonic-naive control subjects. Besides these empirical data, also theoretical
      considerations contradict an isomorphism between features of REM sleep dreaming
      and mnemonic principles. 

PMID- 24304758
TI  - Beware of being captured by an analogy: dreams are like many things.
AB  - Classic traditions have linked dreams to memory (e.g., "dreaming is another kind
      of remembering" [Freud 1918/1955]) and modern notions like implicit memory
      subsume dreaming by definition. Llewellyn develops the more specific thesis that
      rapid eye movement (REM) dreams, because of their similarities to mnemonic
      techniques, have the function of elaboratively encoding episodic memories. This
      proposal is premature, requiring exigent testing. Other analogs of dreams, for
      example, jokes, do not invoke function but do contribute to dream science. 

PMID- 24304759
TI  - The seahorse, the almond, and the night-mare: elaborative encoding during sleep
      paralysis hallucinations?
AB  - Llewellyn's proposal that rapid eye movement (REM) dreaming reflects elaborative
      encoding mediated by the hippocampus ("seahorse") offers an interesting
      perspective for understanding hallucinations accompanying sleep paralysis (SP;
      "night-mare"). SP arises from anomalous intrusion of REM processes into waking
      consciousness, including threat-detection systems mediated by the amygdala
      ("almond"). Unique aspects of SP hallucinations offer additional prospects for
      investigation of Llewellyn's theory of elaborative encoding. 

PMID- 24304760
TI  - Ontological significance of the dream world.
AB  - Sometimes while sleeping we find ourselves thrown amidst an authentic, albeit
      bizarre, world. The process of integration by means of which memory elements
      might be fabricated into a seamless world indistinguishable from the world of
      waking life is not explained by Llewellyn, who focuses instead on the elaborative
      encoding of memories. Ontological implications of the sometimes indiscernibility
      of wake and dream worlds are considered. 

PMID- 24304761
TI  - A three-legged stool needs a stronger third leg.
AB  - Whereas the target article stresses the neurobiology and psychology of dreams,
      this commentary emphasizes that the role of dreams in emotional integration and
      adaptation contributes to a fuller understanding of dreaming and memory. The
      dream presented in the target article is used, within the constraints of space,
      as a possible example of a broader approach to dream material. 

PMID- 24304762
TI  - The ancient art of memory.
AB  - Revision of Freud's theory requires a new way of seeking dream meaning. With the
      idea of elaborative encoding, Sue Llewellyn has provided a method of dream
      interpretation that takes into account both modern sleep science and the ancient
      art of memory. Her synthesis is elegant and compelling. But is her hypothesis
      testable? 

PMID- 24304763
TI  - REM sleep and dreaming functions beyond reductionism.
AB  - Brain activation patterns and mental, electrophysiological, and neurobiological
      features of rapid eye movement (REM) sleep suggest more functions than only
      elaborative encoding. Hence, the periodic occurrence of REM sleep episodes and
      dreaming may be regarded as a recurrent adaptive interference, which incorporates
      recent memories into a broader vital context comprising emotions, basic needs and
      individual genetic traits. 

PMID- 24304764
TI  - The spaces left over between REM sleep, dreaming, hippocampal formation, and
      episodic autobiographical memory.
AB  - It is argued that Llewellyn's hypothesis about the lack of rapid eye movement
      (REM)-sleep dreaming leading to loss of personal identity and deficits in
      episodic memory, affectivity, and prospection is insufficiently grounded because
      it does not integrate data from neurodevelopmental studies and makes reference to
      an outdated definition of episodic memory. 

PMID- 24304765
TI  - The secret is at the crossways: hodotopic organization and nonlinear dynamics of
      brain neural networks.
AB  - By integrating the classic psychological principles of ancient art of memory
      (AAOM) with the most recent paradigms in cognitive neuroscience (i.e., the
      concepts of hodotopic organization and nonlinear dynamics of brain neural
      networks), Llewellyn provides an up-to-date model of the complex psychological
      relationships between memory, imagination, and dreams in accordance with current
      state-of-the-art principles in neuroscience. 

PMID- 24304766
TI  - The method of loci (MoL) and memory consolidation: dreaming is not MoL-like.
AB  - Certain method of loci (MoL) prerequisites--familiar, coherently ordered
      locations--should appear during dreaming if the latter is, in fact, elaborative
      memory encoding as hypothesized by Llewellyn. A review of the literature suggests
      that dreamed locations are neither familiar nor coherently ordered and thus
      unsuitable for facilitating memory in this sense. This conclusion converges with
      other evidence that episodic memory is dependent upon non-rapid eye movement
      (NREM), rather than REM, sleep.

PMID- 24304767
TI  - Dreams, mnemonics, and tuning for criticality.
AB  - According to the tuning-for-criticality theory, the essential role of sleep is to
      protect the brain from super-critical behaviour. Here we argue that this
      protective role determines the content of dreams and any apparent relationship to
      the art of memory is secondary to this. 

PMID- 24304768
TI  - From Freud to acetylcholine: does the AAOM suffice to construct a dream?
AB  - Toward illuminating the structure of Llewellyn's dream theory, I compare it in
      formal terms to Freud's dream theory. An alternative to both of these dream
      machines, grounded in the distribution of cholinergic activation in the central
      nervous system, is presented. It is suggested that neither "high" nor "low" dream
      theory is sufficient to account for the properties of dreams. 

PMID- 24304769
TI  - Studying the relationship between dreaming and sleep-dependent memory processes:
      methodological challenges.
AB  - The hypothesis that dreaming is involved in off-line memory processing is
      difficult to test because major methodological issues have to be addressed, such
      as dream recall and the effect of remembered dreams on memory. It would be
      fruitful--in addition to studying the ancient art of memory (AAOM) in a scanner-
      to study the dreams of persons who use AAOM regularly.

PMID- 24304770
TI  - Dreaming is not controlled by hippocampal mechanisms.
AB  - Links with the Humanities are to be welcomed, but they cannot be exempted from
      normal scientific criteria. Any hypothesis regarding the function of dreams that
      is premised on rapid eye movement (REM)/dream isomorphism is unsupportable on
      empirical grounds. Llewellyn's hypothesis has the further problem of counter
      evidence in respect of its claim that dreaming relies upon hippocampal functions.
      The hypothesis also lacks face validity. 

PMID- 24304771
TI  - REM sleep, hippocampus, and memory processing: insights from functional
      neuroimaging studies.
AB  - Neuroimaging studies show that episodic memory encoding is associated with
      increased activity in hippocampus and lateral prefrontal cortex; however, the
      latter structure shows decreased activity in rapid eye movement (REM) sleep.
      Together with few episodic memory traces in REM sleep, and REM sleep deprivation
      affecting hippocampus-independent emotional processes, this argues for generic
      information processing in REM sleep rather than linking episodic memory traces. 

PMID- 24304772
TI  - Dissociative symptoms and REM sleep.
AB  - Llewellyn has written a fascinating article about rapid eye movement (REM) dreams
      and how they promote the elaborative encoding of recent memories. The main
      message of her article is that hyperassociative and fluid cognitive processes
      during REM dreaming facilitate consolidation. We consider one potential
      implication of this analysis: the possibility that excessive or out-of-phase REM
      sleep fuels dissociative symptomatology. Further research is warranted to explore
      the psychopathological ramifications of Llewellyn's theory. 

PMID- 24304773
TI  - Elaborative encoding during REM dreaming as prospective emotion regulation.
AB  - Rapid eye movement (REM) dreaming results in "emotionally intelligent encoding,"
      according to the target article. Building on this, we argue that elaborative
      encoding alters emotional processing of upcoming events and thereby functions as
      prospective emotion regulation. After elaborative encoding, future events are
      appraised differently and result in a redirected emotional response. Disturbed
      elaborative encoding might be relevant for emotional dysregulation in
      psychopathology. 

PMID- 24304774
TI  - Minding the dream self: perspectives from the analysis of self-experience in
      dreams.
AB  - Can ancient art of memory (AAOM) principles explain the function of dreaming? The
      analysis of self-experience in dreams suggests that the answer is no: The
      phenomenal dream self lacks certain dimensions that are crucial for the efficacy
      of AAOM in wakefulness. However, the comparison between dreams and AAOM may be
      fruitful by suggesting new perspectives for the study of lucid dreaming as well
      an altered perspective on the efficacy of AAOM itself. 

PMID- 24304776
TI  - Monotonous tasks require self-control because they interfere with endogenous
      reward.
AB  - Self-control is a necessary component of subjective effort, but it depends only
      on farsighted motivation, with no additional, depletable resource. The
      aversiveness of boring tasks probably comes from their interference with
      endogenous reward, a new and potentially controversial concept. The self-control
      needed to stick with any kind of aversive experience increases as the values of
      the competing motives draw closer together. 

PMID- 24304777
TI  - Difficulty matters: unspecific attentional demands as a major determinant of
      performance highlighted by clinical studies.
AB  - The cognitive impairments shown by brain-damaged patients emphasize the role of
      task difficulty as a major determinant for performance. We discuss the proposal
      of Kurzban et al. in light of our findings on right-hemisphere-damaged patients,
      who show increasing awareness deficits for the contralesional hemispace when
      engaged with resource-consuming dual tasks. This phenomenon is readily explained
      by the assumption of unspecific depletable resources. 

PMID- 24304778
TI  - An addition to Kurzban et al.'s model: thoroughness of cost-benefit analyses
      depends on the executive tasks at hand.
AB  - Though Kurzban et al.'s model explains a considerable set of empirical findings,
      it cannot accommodate other results without relying on extra assumptions. We
      offer an addition to the model, and suggest that cost-benefit analyses themselves
      depend on executive function, and therefore can be biased. The adapted model
      allows for explaining depletion effects, as well as their reversals, documented
      in the literature. 

PMID- 24304775
TI  - An opportunity cost model of subjective effort and task performance.
AB  - Why does performing certain tasks cause the aversive experience of mental effort
      and concomitant deterioration in task performance? One explanation posits a
      physical resource that is depleted over time. We propose an alternative
      explanation that centers on mental representations of the costs and benefits
      associated with task performance. Specifically, certain computational mechanisms,
      especially those associated with executive function, can be deployed for only a
      limited number of simultaneous tasks at any given moment. Consequently, the
      deployment of these computational mechanisms carries an opportunity cost--that
      is, the next-best use to which these systems might be put. We argue that the
      phenomenology of effort can be understood as the felt output of these
      cost/benefit computations. In turn, the subjective experience of effort motivates
      reduced deployment of these computational mechanisms in the service of the
      present task. These opportunity cost representations, then, together with other
      cost/benefit calculations, determine effort expended and, everything else equal,
      result in performance reductions. In making our case for this position, we review
      alternative explanations for both the phenomenology of effort associated with
      these tasks and for performance reductions over time. Likewise, we review the
      broad range of relevant empirical results from across sub-disciplines, especially
      psychology and neuroscience. We hope that our proposal will help to build links
      among the diverse fields that have been addressing similar questions from
      different perspectives, and we emphasize ways in which alternative models might
      be empirically distinguished.

PMID- 24304779
TI  - Local resource depletion hypothesis as a mechanism for action selection in the
      brain.
AB  - As a comment on Kurzban et al.'s opportunity cost model, we propose an
      alternative view of mental effort and the action selection mechanism in the
      brain. Our hypothesis utilizes local resource depletion within neuronal networks,
      which justifies from a neurophysiological perspective why mental fatigue
      diminishes after switching to a novel task and explains action selection by means
      of neural competition theory. 

PMID- 24304780
TI  - Is ego depletion too incredible? Evidence for the overestimation of the depletion
      effect.
AB  - The depletion effect, a decreased capacity for self-control following previous
      acts of self-control, is thought to result from a lack of necessary
      psychological/physical resources (i.e., "ego depletion"). Kurzban et al. present
      an alternative explanation for depletion; but based on statistical techniques
      that evaluate and adjust for publication bias, we question whether depletion is a
      real phenomenon in need of explanation. 

PMID- 24304781
TI  - Can tasks be inherently boring?
AB  - Kurzban et al. argue that the experiences of "effort," "boredom," and "fatigue"
      are indications that the costs of a task outweigh its benefits. Reducing the
      costs of tasks to "opportunity costs" has the effect of rendering tasks costless
      and of denying that they can be inherently boring or tedious, something that
      "vigilance tasks" were intentionally designed to be. 

PMID- 24304782
TI  - Maximising utility does not promote survival.
AB  - We argue that maximising utility does not promote survival. Hence, there is no
      reason to expect people to modulate effort according to a task's opportunity
      costs. There is also no reason why our evaluation of the marginal opportunity
      costs of tasks should predictably rise with repetition. Thus, the opportunity
      cost model cannot explain why tasks typically become harder over time. 

PMID- 24304783
TI  - An interoceptive neuroanatomical perspective on feelings, energy, and effort.
AB  - A homeostatic energy model of awareness proposes that the anterior insular cortex
      engenders feelings that provide an amodal valuation of homeostatic energy
      utilization in an opponent, bivalent emotional control system. Feelings are the
      "common currency" which enable optimal utilization in the physical and mental
      behavior of a highly social primate. This model offers a different perspective. 

PMID- 24304784
TI  - Opportunity cost calculations only determine justified effort--or, what happened
      to the resource conservation principle?
AB  - We welcome the development of a new model on effort and performance and the
      critique on existing resource-based models. However, considering the vast
      evidence for the significant impact of experienced task demand on resource
      allocation, we conclude that Kurzban et al.'s opportunity cost model is only
      valid for one performance condition: if task demand is unknown or unspecified. 

PMID- 24304785
TI  - The opportunity cost model: automaticity, individual differences, and self
      control resources.
AB  - I contend that Kurzban et al.'s model is silent on three issues. First, the
      extent to which opportunity-cost computations are automatic or deliberative is
      unclear. Second, the role of individual differences in biasing opportunity-cost
      computations needs elucidating. Third, in the absence of "next-best" tasks, task
      persistence will be indefinite, which seems unfeasible, so perhaps integration
      with a limited-resource account is necessary. 

PMID- 24304786
TI  - Give me strength or give me a reason: self-control, religion, and the currency of
      reputation.
AB  - We show that Kurzban et al.'s approach illuminates the relationship between
      religion and self-control. Whereas resource-depletion theorists suggest religion
      replenishes self-control resources ("strength"), we submit that religious cues
      make people feel observed, giving them "reason" to persevere, and we describe an
      experiment that supports our interpretation. Finally, we question the claim that
      subjective fatigue is a signal to redeploy resources. 

PMID- 24304787
TI  - Depletable resources: necessary, in need of fair treatment, and multi-functional.
AB  - I make three points. First, processors and depletable resources should not be
      regarded as alternative means of processing information: they are both necessary.
      Second, comparing a processor account with a rational allocation mechanism to a
      depletable-resources account without one is not a fair comparison. Third,
      depletable resources can act as signals as well as fuels. 

PMID- 24304788
TI  - Competing goals draw attention to effort, which then enters cost-benefit
      computations as input.
AB  - Different to Kurzban et al., we conceptualize the experience of mental effort as
      the subjective costs of goal pursuit (i.e., the amount of invested resources
      relative to the amount of available resources). Rather than being an output of
      computations that compare costs and benefits of the target and competing goals,
      effort enters these computations as an input. 

PMID- 24304789
TI  - Persisting through subjective effort: a key role for the anterior cingulate
      cortex?
AB  - One shortcoming of Kurzban et al.'s model is that it is not clear how animals
      persist through subjectively effortful tasks, particularly over a long time
      course. We suggest that the anterior cingulate cortex plays a critical role by
      encoding the utility of an action, and signalling where efforts should be best
      directed based on previous and prospected experience. 

PMID- 24304790
TI  - On treating effort as a dynamically varying cost input.
AB  - Kurzban et al.'s framework may be extended in fruitful ways by treating effort
      also as a cost input that affects the utility computation of a given option
      (rather than only as the output of a utility comparison between options). The
      weight people assign to effort as a cost may vary dynamically as a function of
      situational and dispositional factors. 

PMID- 24304791
TI  - Theories of anterior cingulate cortex function: opportunity cost.
AB  - The target article highlights the role of the anterior cingulate cortex (ACC) in
      conflict monitoring, but ACC function may be better understood in terms of the
      hierarchical organization of behavior. This proposal suggests that the ACC
      selects extended goal-directed actions according to their learned costs and
      benefits and executes those behaviors subject to depleting resources. 

PMID- 24304792
TI  - Formal models of "resource depletion".
AB  - The opportunity cost model (OCM) aims to explain various phenomena, among which
      the finding that performance degrades if executive functions are used repeatedly
      ("resource depletion"). We argue that an OCM account of resource depletion
      requires two unlikely assumptions, and we discuss an alternative that does not
      require these assumptions. This alternative model describes the interplay between
      executive function and motivation. 

PMID- 24304793
TI  - Beyond simple utility in predicting self-control fatigue: a proximate alternative
      to the opportunity cost model.
AB  - The opportunity cost model offers an ultimate explanation of ego depletion that
      helps to move the field beyond biologically improbable resource accounts. The
      model's more proximate explanation, however, falls short of accounting for much
      data and is based on an outdated view of human rationality. We suggest that our
      own process model offers a better proximate account of self-control fatigue. 

PMID- 24304794
TI  - Opportunity prioritization, biofunctional simultaneity, and psychological mutual
      exclusion.
AB  - We argue that prioritization, simultaneity, and mutual exclusion are mind-body
      integration functions that can't be addressed meaningfully at the psychological
      (computational) level alone. We describe the outlook for an integration between
      Kurzban et al.'s profound discussion of opportunity cost/benefit prioritization
      and decades of related development in biofunctional science. 

PMID- 24304795
TI  - The intrinsic cost of cognitive control.
AB  - Kurzban and colleagues carry forward an important contemporary movement in
      cognitive control research, tending away from resource-based models and toward a
      framework focusing on motivation or value. However, their specific proposal,
      centering on opportunity costs, appears problematic. We favor a simpler view,
      according to which the exertion of cognitive control carries intrinsic subjective
      costs. 

PMID- 24304796
TI  - Beyond dopamine: the noradrenergic system and mental effort.
AB  - An opportunity cost model of effort requires flexible integration of valuation
      and self-control systems. Reciprocal connections between these networks and
      brainstem neuromodulatory systems are likely to provide the signals that affect
      subsequent persistence or failure when faced with effort challenges. The
      interaction of these systems should be taken into account to strengthen a
      normative neural model of effort. 

PMID- 24304797
TI  - An expanded perspective on the role of effort phenomenology in motivation and
      performance.
AB  - Kurzban and colleagues propose that experiences of effort alter motivations to
      persist during goal pursuit by highlighting costs of persistence. I expand this
      proposal by discussing how effort experiences (a) not only influence, but can be
      influenced by motivations to persist on a goal; and (b) not only highlight costs
      that undermine persistence, but can also signal progress and increase
      persistence. 

PMID- 24304798
TI  - Willpower is not synonymous with "executive function".
AB  - Kurzban et al. make a convincing case against the idea that willpower is a
      depleting resource. However, they do not advance a positive account of willpower.
      Rather than treating "willpower" as a synonym of "executive function," we argue
      that the term willpower should be designated for mechanisms individuals deploy to
      reduce dynamic inconsistency in their behavior. 

PMID- 24304799
TI  - Effort aversiveness may be functional, but does it reflect opportunity cost?
AB  - Though the aversiveness of effort may indeed serve in selecting tasks for
      executive attention, the notion that it reflects opportunity costs is
      questionable: The potency of distractions in real-life situations is not
      regularly related with the potential benefit from attending to them. 

PMID- 24304800
TI  - The costs of giving up: action versus inaction asymmetries in regret.
AB  - Kurzban et al.'s opportunity cost model of mental effort relies heavily on
      counterfactual thinking. We suggest that a closer inspection of the role of
      counterfactual emotions, and particularly of action/inaction asymmetries in
      anticipated regret, may be important in understanding the role of opportunity
      costs in decisions to persist with a current task. 

PMID- 24304801
TI  - Mental effort and fatigue as consequences of monotony.
AB  - Kurzban et al. associate mental effort and fatigue with a hypothetical mechanism
      able to estimate the utilities of possible actions and then select the action
      with a maximal utility. However, this approach faces fundamental problems. In my
      opinion, mental effort and fatigue are results of a conflict between the monotony
      of long-term activities and the novelty-processing systems. 

PMID- 24304802
TI  - Subjective effort derives from a neurological monitor of performance costs and
      physiological resources.
AB  - Kurzban et al.'s expectancy-value mechanism of effort allocation seems relevant
      in situations when familiar tasks are initiated. However, we think additional
      mechanisms are important when people continue with a task for a prolonged time.
      These mechanisms, which are particularly relevant for performance of novel or
      urgent tasks, involve neural systems that track performance costs and resources. 

PMID- 24304803
TI  - The economics of cognitive effort.
AB  - If cognitive effort indexes opportunity costs, it should be investigated like
      other cost factors including risk and delay. We discuss recent methodological
      advances in behavioral economics and neuroeconomics, highlighting our own work in
      measuring the subjective (economic) value of cognitive effort. We discuss the
      implications of Kurzban et al.'s proposal and how some of its predictions may be
      untestable without behavioral economic formalisms.

PMID- 24304804
TI  - Effort processes in achieving performance outcomes: interrelations among and
      roles of core constructs.
AB  - We address points of confusion pertaining to interrelations among and roles of
      core constructs involved in the production of performance outcomes. We do so
      informed by the body of work derived from Brehm's seminal motivation intensity
      theory--in particular an elaboration from the theory concerned with fatigue
      influence on effort and associated cardiovascular responses in people confronted
      with performance challenges.

PMID- 24304805
TI  - Persistence: what does research on self-regulation and delay of gratification
      have to say?
AB  - Despite the simplicity of Kurzban et al.'s framework, we argue that important
      information is lost in their simplification. We discuss research on delay of
      gratification and self-regulation that identifies key situational and
      psychological factors affecting how people represent rewards and costs. These
      factors affect the expected utilities of behavioral options and thus dramatically
      influence whether individuals persist on a difficult task. 

PMID- 24304806
TI  - In vivo evaluation of wound bed reaction and graft performance after cold skin
      graft storage: new targets for skin tissue engineering.
AB  - Surplus harvested skin grafts are routinely stored at 4 to 6 degrees C in saline
      for several days in plastic surgery. The purpose of this study was to evaluate
      the influence of storage on human skin graft performance in an in vivo intravital
      microscopic setting after transplantation. Freshly harvested human full-thickness
      skin grafts and split-thickness skin grafts (STSGs) after storage of 0, 3, or 7
      days in moist saline at 4 to 6 degrees C were transplanted into the modified
      dorsal skinfold chamber, and intravital microscopy was performed to evaluate
      vessel morphology and angiogenic change of the wound bed. The chamber tissue was
      harvested 10 days after transplantation for evaluation of tissue integrity and
      inflammation (hematoxylin and eosin) as well as for immunohistochemistry (human
      CD31, murine CD31, Ki67, Tdt-mediated dUTP-biotin nick-end labelling). Intravital
      microscopy results showed no differences in the host angiogenic response between
      fresh and preserved grafts. However, STSGs and full-thickness skin grafts
      exhibited a trend toward different timing and strength in capillary widening and
      capillary bud formation. Preservation had no influence on graft quality before
      transplantation, but fresh STSGs showed better quality 10 days after
      transplantation than 7-day preserved grafts. Proliferation and apoptosis as well
      as host capillary in-growth and graft capillary degeneration were equal in all
      groups. These results indicate that cells may activate protective mechanisms
      under cold conditions, allowing them to maintain function and morphology.
      However, rewarming may disclose underlying tissue damage. These findings could be
      translated to a new approach for the design of full-thickness skin substitutes. 

PMID- 24304807
TI  - Probing the compressibility of tumor cell nuclei by combined atomic force
      confocal microscopy.
AB  - The cell nucleus is the largest and stiffest organelle rendering it the limiting
      compartment during migration of invasive tumor cells through dense connective
      tissue. We here describe a combined atomic force microscopy (AFM)-confocal
      microscopy approach for measurement of bulk nuclear stiffness together with
      simultaneous visualization of the cantilever-nucleus contact and the fate of the
      cell. Using cantilevers functionalized with either tips or beads and spring
      constants ranging from 0.06-10 N m(-1), force-deformation curves were generated
      from nuclear positions of adherent HT1080 fibrosarcoma cell populations at
      unchallenged integrity, and a nuclear stiffness range of 0.2 to 2.5 kPa was
      identified depending on cantilever type and the use of extended fitting models.
      Chromatin-decondensating agent trichostatin A (TSA) induced nuclear softening of
      up to 50%, demonstrating the feasibility of our approach. Finally, using a stiff
      bead-functionalized cantilever pushing at maximal system-intrinsic force, the
      nucleus was deformed to 20% of its original height which after TSA treatment
      reduced further to 5% remaining height confirming chromatin organization as an
      important determinant of nuclear stiffness. Thus, combined AFM-confocal
      microscopy is a feasible approach to study nuclear compressibility to complement
      concepts of limiting nuclear deformation in cancer cell invasion and other
      biological processes.

PMID- 24304808
TI  - Air pollution exposure as a risk factor for cardiovascular disease morbidity and
      mortality.
AB  - There is growing evidence of an association between increasing exposure to air
      pollutants (both short-term and long-term exposures) and elevated risk of
      mortality and incidence of cardiovascular diseases in certain high-risk
      populations and throughout different geographic regions. The pathophysiologic
      mechanisms of air pollutant-induced cardiovascular morbidity and mortality are
      actively being studied, with autonomic system dysregulation and inflammatory
      pathway activation believed to be among the key culprits. Policy changes at the
      local and global levels are addressing the need for more stringent air pollution
      standards. These initiatives are projected to lower costs and improve health
      outcomes. In this review, we examine some major studies of the cardiovascular
      health impacts of air pollution. 

PMID- 24304809
TI  - New antiobesity agents: lorcaserin (Belviq) and phentermine/topiramate ER
      (Qsymia).
AB  - Obesity is a risk factor for a wide range of conditions, including cardiovascular
      disease. Although lifestyle modifications remain the cornerstone for the
      management of obesity, pharmacologic agents may be a helpful addition to patients
      who have comorbidities and do not respond adequately to diet and exercise.
      Lorcaserin and phentermine/topiramate ER are 2 long-awaited agents, approved in
      2012 for obesity management, 13 years since orlistat received US Food and Drug
      Administration approval in 1999. Lorcaserin is a serotonin agonist, whereas
      phentermine/topiramate is a combination of a sympathomimetic agent and an
      antiepileptic drug; both these agents have been shown to reduce weight
      significantly and improve cardiovascular and metabolic parameters, such as blood
      pressure, lipids, and HbA1C. This article reviews the pharmacology and clinical
      efficacy and safety of each of these agents. The differences among the three
      available agents for long-term management of obesity will also be examined. 

PMID- 24304810
TI  - Erdheim-Chester disease and pituitary involvement: a unique case and the
      literature.
AB  - An early thirties man diagnosed with Erdheim-Chester disease (ECD) was
      simultaneously disclosed to have hypogonadotropic hypogonadism, central adrenal
      insufficiency, and GH deficiency in addition to central diabetes insipidus (CDI).
      Pituitary magnetic resonance imaging (MRI) showed swelling in the stalk,
      enlargement of the anterior lobe with delayed enhancement, and loss of high
      intensity of the posterior lobe on T1-weighted images, suggesting of pituitary
      involvement of ECD. Three months after starting treatment with interferon alpha
      and zoledronic acid, polyuria and polydipsia were ameliorated without DDAVP,
      accompanied with improvement of MRI. Simultaneously technetium-99m bone
      scintigraphy showed improvement, accompanied with a relief of bone pain and high
      fever. In contrast, he developed secondary hypothyroidism with slight enlargement
      of anterior pituitary gland without relapse of CDI, suggesting of different
      responses to treatment with interferon alpha between anterior pituitary lobe and
      posterior one. So far he continues to be replaced with deficient hormone
      replacement therapy. As for bone pain, it remains to be controlled with the
      decreased levels of bone resorption marker with decreased abnormal uptake in bone
      scintigraphy although zoledronic acid was discontinued for osteonecrosis of the
      jaw. For four years, he has not showed new involvement at other organs besides
      bones and the pituitary. While CDI is known to be very common in ECD, improvement
      of CDI has been reported in a few cases. Other endocrine manifestations,
      especially with detailed endocrine status, have been also reported in limited
      cases. Thus we report this case and review the literature. 

PMID- 24304811
TI  - Methodological concerns about studies on oseltamivir for flu.

PMID- 24304812
TI  - Biochemical and molecular characterization of Treponema phagedenis-like
      spirochetes isolated from a bovine digital dermatitis lesion.
AB  - BACKGROUND: Bovine papillomatous digital dermatitis (DD) is the leading cause of
      lameness in dairy cattle and represents a serious welfare and economic burden.
      Found primarily in high production dairy cattle worldwide, DD is characterized by
      the development of an often painful red, raw ulcerative or papillomatous lesion
      frequently located near the interdigital cleft and above the bulbs of the heel.
      While the exact etiology is unknown, several spirochete species have been
      isolated from lesion material. Four isolates of Treponema phagedenis-like
      spirochetes were isolated from dairy cows in Iowa. Given the distinct differences
      in host, environmental niche, and disease association, a closer analysis of
      phenotypic characteristics, growth characteristics, and genomic sequences of T.
      phagedenis, a human genitalia commensal, and the Iowa DD isolates was undertaken.
      RESULTS: Phenotypically, these isolates range from 8.0 to 9.7 MUm in length with
      6-8 flagella on each end. These isolates, like T. phagedenis, are strictly
      anaerobic, require serum and volatile fatty acids for growth, and are capable of
      fermenting fructose, mannitol, pectin, mannose, ribose, maltose, and glucose.
      Major glucose fermentation products produced are formate, acetate, and butyrate.
      Further study was conducted with a single isolate, 4A, showing an optimal growth
      pH of 7.0 (range of 6-8.5) and an optimal growth temperature of 40  degrees C
      (range of 29  degrees C-43  degrees C). Comparison of partial genomic contigs of
      isolate 4A and contigs of T. phagedenis F0421 revealed > 95% amino acid sequence
      identity with amino acid sequence of 4A. In silico DNA-DNA whole genome
      hybridization and BLAT analysis indicated a DDH estimate of >80% between isolate
      4A and T. phagedenis F0421, and estimates of 52.5% or less when compared to the
      fully sequenced genomes of other treponeme species. CONCLUSION: Using both
      physiological, biochemical and genomic analysis, there is a lack of evidence for
      difference between T. phagedenis and isolate 4A. The description of Treponema
      phagedenis should be expanded from human genital skin commensal to include being
      an inhabitant within DD lesions in cattle.

PMID- 24304813
TI  - Route optimisation and solving Zermelo's navigation problem during long distance
      migration in cross flows.
AB  - The optimum path to follow when subjected to cross flows was first considered
      over 80 years ago by the German mathematician Ernst Zermelo, in the context of a
      boat being displaced by ocean currents, and has become known as the 'Zermelo
      navigation problem'. However, the ability of migrating animals to solve this
      problem has received limited consideration, even though wind and ocean currents
      cause the lateral displacement of flyers and swimmers, respectively, particularly
      during long-distance journeys of 1000s of kilometres. Here, we examine this
      problem by combining long-distance, open-ocean marine turtle movements (obtained
      via long-term GPS tracking of sea turtles moving 1000s of km), with a high
      resolution basin-wide physical ocean model to estimate ocean currents. We provide
      a robust mathematical framework to demonstrate that, while turtles eventually
      arrive at their target site, they do not follow the optimum (Zermelo's) route.
      Even though adult marine turtles regularly complete incredible long-distance
      migrations, these vertebrates primarily rely on course corrections when entering
      neritic waters during the final stages of migration. Our work introduces a new
      perspective in the analysis of wildlife tracking datasets, with different animal
      groups potentially exhibiting different levels of complexity in goal attainment
      during migration.

PMID- 24304814
TI  - miR-223 regulates cell growth and targets proto-oncogenes in mycosis
      fungoides/cutaneous T-cell lymphoma.
AB  - The pathogenesis of the cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF),
      is unclear. MicroRNA (miRNA) are small noncoding RNAs that target mRNA leading to
      reduced mRNA translation. Recently, specific miRNA were shown to be altered in
      CTCL. We detected significantly reduced expression of miR-223 in early-stage MF
      skin, and further decreased levels of miR-223 in advanced-stage disease. CTCL
      peripheral blood mononuclear cells and cell lines also had reduced miR-223 as
      compared with controls. Elevated expression of miR-223 in these cell lines
      reduced cell growth and clonogenic potential, whereas inhibition of miR-223
      increased cell numbers. Investigations into putative miR-223 targets with
      oncogenic function, including E2F1 and MEF2C, and the predicted miR-223 target,
      TOX, revealed that all three were targeted by miR-223 in CTCL. E2F1, MEF2C, and
      TOX proteins were decreased with miR-223 overexpression, whereas miR-223
      inhibition led to increased protein levels in CTCL. In addition, we showed that
      the 3'-UTR of TOX mRNA was a genuine target of miR-223. Therefore, reduced levels
      of miR-223 in MF/CTCL lead to increased expression of E2F1, MEF2C, and TOX, which
      likely contributes to the development and/or progression of CTCL. Thus, miR-223
      and its targets may be useful for the development of new therapeutics for
      MF/CTCL. 

PMID- 24304815
TI  - Melanoma patients under vemurafenib: prospective follow-up of melanocytic lesions
      by digital dermoscopy.
AB  - Second primary melanomas (SPMs) induced by vemurafenib have been recently
      described. The aim of this study was to define the dermoscopical signs of
      melanoma in this context. Patients underwent a total body examination before
      receiving vemurafenib. Each single melanocytic lesion was registered before
      therapy by digital dermoscopy (DD), and then repeated monthly until therapy
      disruption. Forty-two patients were included, the mean duration of follow-up was
      6.7 months, and a mean number of 51 lesions per patients were captured and
      followed. A total number of 2,155 lesions were recorded, of which 56.1% presented
      at least one change during the study. More common changes concerned the color of
      the lesions (up to 15%) and appearance or disappearance of globules (14.6%).
      Thirty-six of the melanocytic lesions were surgically excised, 21 were classified
      as a nevus, 1 was a lentigo, and 14 as a second new primary melanoma (occurring
      in 21% of our patients). DD allowed us to excise only 36/2,155 (1.6%) of the
      lesions and permitted us to detect 14 SPM in the 42 patients with a highly
      efficient malignant/benign ratio of 63.6%. Although vemurafenib is now tested in
      an adjuvant setting DD should be systematically used in order to accurately
      detect SPM and reduce the number of unnecessary excisions. 

PMID- 24304816
TI  - A fibronectin peptide redirects PDGF-BB/PDGFR complexes to macropinocytosis-like
      internalization and augments PDGF-BB survival signals.
AB  - Growth factor-binding domains identified in various extracellular matrix proteins
      have been shown to regulate growth factor activity in many ways. Recently, we
      identified a fibronectin peptide (P12) that can bind platelet-derived growth
      factor BB (PDGF-BB) and promote adult human dermal fibroblast (AHDF) survival
      under stress. In vivo experiments in a porcine burn injury model showed that P12
      limited burn injury progression, suggesting an active role in tissue survival. In
      this report, we explored the molecular mechanism of this peptide in ADHF under
      nutrient deprivation. Our results showed that P12 acted like some cell
      penetrating peptides in that it redirected ligand-bound PDGF receptor (PDGFR)
      from the clathrin-dependent endocytic pathway to a slower, macropinocytosis-like
      pathway. P12 slowed internalization and degradation of PDGF-BB, augmented its
      survival signals, and promoted cell survival after nutrient removal. Our findings
      demonstrate a mechanism for a potential therapeutic peptide that increases cell
      and tissue survival by acting as a cofactor to PDGF-BB. 

PMID- 24304818
TI  - Central and peripheral effects of Sutherlandia frutescens on the response to
      acute psychological stress.
AB  - Sutherlandia frutescens is widely used in indigenous medicine for the treatment
      of stress- and anxiety-related disorders, and although anecdotal evidence has
      been scientifically confirmed, relatively little data are available on its
      potential mechanisms of action. We manipulated a rodent model of acute
      psychological stress by acutely administering a low dose (4 mg/kg body mass) of
      S. frutescens extract 30 min prior to stress exposure (1 h restraint), to
      elucidate both its central and peripheral mechanisms of action in the context of
      acute stress. After 1 h of exposure to stress, acute restraint resulted in a
      significant increase in plasma corticosterone levels (56 +/- 33 versus 499 +/- 50
      ng/ml; P < 0.0001) and anterior pituitary adrenocorticotropic hormone (ACTH)
      levels (0.066 +/- 0.017 versus 0.202 +/- 0.033% fluorescent area; P = 0.07),
      while decreasing hippocampal glucocorticoid receptor (GR) and gamma-aminobutyric
      acid (GABA)(A)alpha1 receptor levels (both P < 0.05). While the low dose of S.
      frutescens administered did not seem to have an effect on the down-stream stress
      response, it abolished the stress-induced down-regulation of GR, in a manner
      independent of GABA(A)alpha1 receptor. Results suggest a non-sedative effect of
      low-dose S. frutescens and points to central mechanisms of action that is in
      support of the anecdotal claims for its effectiveness as complimentary treatment
      in chronic stress-associated diseases. 

PMID- 24304817
TI  - Connexin a check-point component of cell apoptosis in normal and
      physiopathological conditions.
AB  - Gap junction protein connexins (Cxs) play essential roles in cell homeostasis,
      growth, differentiation and death. Therefore, Cx dysfunction has been associated
      with many diseases and with tumor development. Cxs control cell apoptosis through
      different molecular mechanisms. First, gap junction channels classically
      facilitate the influx and flux of apoptotic signals between adjacent cells and
      hemichannels between the intracellular and extracellular environments. Second,
      recent studies demonstrate that Cx proteins, independently from their functional
      role through channels or hemichannels and in conjunction with their
      intracytoplasmic localization, may act as signaling effectors able to activate
      the canonical mitochondrial apoptotic pathway. In the present review, we
      dissected both functions of Cx in apoptosis, providing new avenues for apoptosis
      mediated cancer therapy. 

PMID- 24304819
TI  - Intestinal response to myeloablative chemotherapy in piglets.
AB  - Chemotherapy-induced myeloablation prior to allogeneic hematopoietic stem cell
      transplantation (HSCT) may be associated with severe toxicity. The current
      understanding of the pathophysiology of oral and gastrointestinal (GI) toxicity
      is largely derived from studies in rodents and very little is known from humans,
      especially children. We hypothesized that milk-fed piglets can be used as a
      clinically relevant model of GI-toxicity related to a standard conditioning
      chemotherapy (intravenous busulfan, Bu plus cyclophosphamide, Cy) used prior to
      HSCT. In study 1, dose-response relationships were investigated in three-day-old
      pigs (Landrace * Yorkshire * Duroc, n = 6). Pigs were given one of three
      different dose combinations of Bu and Cy (A: 4 days Bu, 2 * 1.6 mg/kg plus 2 days
      Cy, 60 mg/kg; B: 4 days Bu, 2 * 0.8 mg/kg plus 2 days Cy, 30 mg/kg; C: 2 days Bu
      at 2 * 1.6 mg/kg plus 1 day Cy, 60 mg/kg) and bone marrow was collected on day
      11. Histology of bone marrow samples showed total aplasia after treatment A.
      Using this treatment in study 2, Bu-Cy pigs showed lowered spleen and intestinal
      weights and variable clinical signs of dehydration, sepsis, and pneumonia at
      tissue collection. Oral mucositis was evident as ulcers in the soft palate in 4/9
      Bu-Cy pigs and villus height and brush-border enzyme activities were reduced,
      especially in the proximal intestine. There were no consistent effects on tissue
      cytokine levels (IL-8, IL-6, IL-1beta, TNF-alpha) or blood chemistry values
      (electrolytes, liver transaminases, bilirubin, alkaline phosphatase), except that
      blood iron levels were higher in Bu-Cy pigs. We conclude that a myeloablative Bu
      Cy regimen to piglets results in clinical signs comparable to those seen in
      pediatric patients subjected to myeloablative treatment prior to HSCT. Piglets
      may be used as a model for investigating chemotherapy-induced toxicity and
      dietary and medical interventions. 

PMID- 24304820
TI  - Acquired drug resistance conferred by a KRAS gene mutation following the
      administration of cetuximab: a case report.
AB  - BACKGROUND: Although a number of studies have reported acquired drug resistance
      due to administration of epidermal growth factor receptor antibody inhibitors,
      the underlying causes of this phenomenon remain unclear. CASE PRESENTATION: Here
      we report a case of a 75-year-old man with liver metastasis at 3 years after a
      successful transverse colectomy to treat KRAS wild-type colorectal cancer. While
      initial administration of epidermal growth factor receptor inhibitors proved
      effective, continued use of the same treatment resulted in new peritoneal
      seeding. An acquired KRAS mutation was found in a resected tissue specimen from
      one such area. This mutation, possibly caused by administration of epidermal
      growth factor receptor inhibitors, appears to have conferred drug resistance.
      CONCLUSION: The present findings suggest that administration of epidermal growth
      factor receptor inhibitors results in an acquired KRAS mutation that confers drug
      resistance.

PMID- 24304821
TI  - Relevant gender differences in epidemiological profile, exposure to first
      antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.
AB  - BACKGROUND: The possible differences in the disease spectrum and prognosis of HIV
      infection in women and men is a major point of concern. Women are under
      represented in randomized clinical trials and in some cohorts. Discordant results
      have often been obtained depending on the setting. METHODS: We assessed gender
      differences in clinical and epidemiological features, antiretroviral treatment
      (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects
      in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to
      assess gender effect on time to start ART and time to first ART change, and a Cox
      regression model to estimate gender effect on time to death. RESULTS: Between
      January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study
      entry were included. The trend analysis over time showed the percentage of women
      in the younger (<20 years) and older (>50 years) strata increased significantly
      (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By
      competing risk analysis women started ART earlier than men (adjusted subhazard
      ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of
      these differences were observed. In both cohorts women showed a shorter time to
      the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and
      patient's/physician's decisions as reasons for changing were more frequent in
      women than in men in CoRIS. In the Cox regression model, gender was not
      associated with differences in survival. CONCLUSIONS: In two large cohorts in
      Spain, we observed relevant gender differences in epidemiological characteristics
      and antiretroviral exposure outcomes, while survival differences were not
      attributable to gender.

PMID- 24304822
TI  - FROGG high-risk prostate cancer workshop: patterns of practice and literature
      review: part I: intact prostate.
AB  - Australian and New Zealand radiation oncologists with an interest in uro-oncology
      were invited to participate in a pattern-of-practice survey dealing with the
      management of intact high-risk prostate cancer. Responses from 46 practitioners
      (representing 73% of all potential respondents) revealed that high-dose radiation
      therapy is the standard of care. However, there is variability in practice with
      regard to the methods used to achieve dose escalation, the use of whole-pelvic
      radiation therapy and the optimal duration of androgen deprivation therapy
      employed. A review of the literature outlining the current body of knowledge and
      the planned and ongoing studies in intact high-risk prostate cancer is presented.

PMID- 24304825
TI  - The influence of the treatment response on the impact of resection margin status
      after preoperative chemoradiotherapy in locally advanced rectal cancer.
AB  - BACKGROUND: Circumferential resection margin (CRM) and distal resection margin
      (DRM) have different impact on clinical outcomes after preoperative
      chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of
      resection margin as well as impact of treatment response after preoperative CRT
      was evaluated. METHODS: Total of 403 patients with rectal cancer underwent
      preoperative CRT followed by total mesorectal excision between January 2004 and
      December 2010. After applying the criterion of margin less than 0.5 cm for CRM or
      less than 1 cm for DRM, 151 cases with locally advanced rectal cancer were
      included as a study cohort. All patients underwent conventionally fractionated
      radiation with radiation dose over 50 Gy and concurrent chemotherapy with 5
      fluorouracil or capecitabine. Postoperative chemotherapy was administered to 142
      patients (94.0%). Median follow-up duration was 43.1 months. RESULTS: The 5-year
      overall survival (OS), disease-free survival (DFS), distant metastasis-free
      survival (DMFS) rates, and locoregional control rates (LRC) were 84.5%, 72.8%,
      74.2%, and 86.3%, respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points
      showing maximal difference in a maximally selected rank method. In univariate
      analysis, CRM of 1.5 mm was significantly related with worse clinical outcomes,
      whereas DRM of 7 mm was not. In multivariate analysis, CRM of 1.5 mm, and ypN
      were prognosticators for all studied endpoints. However, CRM was not a
      significant prognostic factor for good responders, defined as patients with near
      total regression or T down-staging, which was found in 16.5% and 40.5% among
      studied patients, respectively. In contrast, poor responders demonstrated a
      significant difference according to the CRM status for all studied end-points.
      CONCLUSIONS: Close CRM, defined as 1.5 mm, was a significant prognosticator, but
      the impact was only prominent for poor responders in subgroup analysis.
      Postoperative treatment strategy may be individualized based on this finding.
      However, findings from this study need to be validated with larger cohort.

PMID- 24304823
TI  - Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent
      nicotine+cocaine self-administration.
AB  - Nicotine dependence and cocaine abuse are major public health problems, and most
      cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce
      both cigarette smoking and cocaine abuse. Varenicline is a clinically available,
      partial agonist at alpha4beta2* and alpha6beta2* nicotinic acetylcholine
      receptors (nAChRs) and a full agonist at alpha7 nAChRs. Varenicline facilitates
      smoking cessation in clinical studies and reduced nicotine self-administration,
      and substituted for the nicotine-discriminative stimulus in preclinical studies.
      The present study examined the effects of chronic varenicline treatment on self
      administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and
      concurrent food-maintained responding by five cocaine- and nicotine-experienced
      adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was
      administered intravenously every 20 min for 23 h each day for 7-10 consecutive
      days. Each varenicline treatment was followed by saline-control treatment until
      food- and drug-maintained responding returned to baseline. During control
      treatment, nicotine+cocaine combinations maintained significantly higher levels
      of drug self-administration than nicotine or cocaine alone (P<0.05-0.001).
      Varenicline dose-dependently reduced responding maintained by nicotine alone
      (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj)
      (P<0.05) with no significant effects on food-maintained responding. However,
      varenicline did not significantly decrease self-administration of a low dose of
      nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg
      cocaine combined with the same doses of nicotine. We conclude that varenicline
      selectively attenuates the reinforcing effects of nicotine alone but not cocaine
      alone, and its effects on nicotine+cocaine combinations are dependent on the dose
      of cocaine. 

PMID- 24304824
TI  - Stress-system genes and life stress predict cortisol levels and amygdala and
      hippocampal volumes in children.
AB  - Depression has been linked to increased cortisol reactivity and differences in
      limbic brain volumes, yet the mechanisms underlying these alterations are
      unclear. One main hypothesis is that stress causes these effects. This is
      supported by animal studies showing that chronic stress or glucocorticoid
      administration can lead to alterations in hippocampal and amygdala structures.
      Relatedly, life stress is cited as one of the major risk factors for depression
      and candidate gene studies have related variation in stress-system genes to
      increased prevalence and severity of depression. The present study tested the
      hypothesis that genetic profile scores combining variance across 10 single
      nucleotide polymorphisms from four stress-system genes (CRHR1, NR3C2, NR3C1, and
      FKBP5) and early life stress would predict increases in cortisol levels during
      laboratory stressors in 120 preschool-age children (3-5 years old), as well as
      hippocampal and amygdala volumes assessed with MRI in these same children at
      school age (7-12 years old). We found that stress-system genetic profile scores
      positively predicted cortisol levels while the number of stressful/traumatic life
      events experienced by 3-5 years old negatively predicted cortisol levels. The
      interaction of genetic profile scores and early life stress predicted left
      hippocampal and left amygdala volumes. Cortisol partially mediated the effects of
      genetic variation and life stress on limbic brain volumes, particularly on left
      amygdala volume. These results suggest that stress-related genetic and early
      environmental factors contribute to variation in stress cortisol reactivity and
      limbic brain volumes in children, phenotypes associated with depression in
      adulthood. 

PMID- 24304827
TI  - Metachronous renal vein and artery injure after percutaneous nephrostolithotomy.
AB  - BACKGROUND: Percutaneous nephrostolithotomy is important approach for kidney
      stones removal. A percutaneous nephrostomy drainage tube placement is an
      effective method to stop venous bleeding. Occasionally, the catheter can pierce
      into the renal parenchyma, and migrate into the renal vein even to the vena cava.
      CASE PRESENTATION: A 66-year-old woman underwent a percutaneous
      nephrostolithotomy for kidney staghorn stone complicating severe bleeding. A
      computed tomography angiography showed the percutaneous nephrostomy drainage tube
      inside the renal vein. The percutaneous nephrostomy drainage tube was withdrawn 3
      cm back to the renal parenchyma/sinus/pelvis in stages with the surgical team on
      standby. Seven days later, the patient developed severe hematuria. Computed
      tomography angiography demonstrated the pseudoaneurysm located near the
      percutaneous nephrostomy drainage tube. Pseudoaneurysm is embolized successfully.
      CONCLUSION: Our case shows intravenous misplacement of the nephrostomy tube and
      subsequent pseudoaneurysm after percutaneous nephrostolithotomy. To our
      knowledge, this seems to be the first documentation of major bleeding from the
      injury to both renal vein and artery. The percutaneous nephrostomy drainage tube
      can be withdrawn back to the renal parenchyma/sinus/pelvis in stages with the
      surgical team on standby, and the withdrawn distance may vary according to
      patient and catheter position.

PMID- 24304826
TI  - Cost-effectiveness of health-related lifestyle advice delivered by peer or lay
      advisors: synthesis of evidence from a systematic review.
AB  - BACKGROUND: Development of new peer or lay health-related lifestyle advisor
      (HRLA) roles is one response to the need to enhance public engagement in, and
      improve cost-effectiveness of, health improvement interventions. This article
      synthesises evidence on the cost-effectiveness of HRLA interventions aimed at
      adults in developed countries, derived from the first systematic review of the
      effectiveness, cost-effectiveness, equity and acceptability of different types of
      HRLA role. METHODS: The best available evidence on the cost-effectiveness of HRLA
      interventions was obtained using systematic searches of 20 electronic databases
      and key journals, as well as searches of the grey literature and the internet.
      Interventions were classified according to the primary health behaviour targeted
      and intervention costs were estimated where necessary. Lifetime health gains were
      estimated (in quality-adjusted life years, where possible), based on evidence of
      effectiveness of HRLAs in combination with published estimates of the lifetime
      health gains resulting from lifestyle changes, and assumptions over relapse.
      Incremental cost-effectiveness ratios are reported. RESULTS: Evidence of the cost
      effectiveness of HRLAs was identified from 24 trials included in the systematic
      review. The interventions were grouped into eight areas. We found little evidence
      of effectiveness of HRLAs for promotion of exercise/improved diets. Where HRLAs
      were effective cost-effectiveness varied considerably: Incremental Cost
      effectiveness Ratios were estimated at L6,000 for smoking cessation; L14,000 for
      a telephone based type 2 diabetes management; and L250,000 or greater for
      promotion of mammography attendance and for HIV prevention amongst drug users. We
      lacked sufficient evidence to estimate ICERs for breastfeeding promotion and
      mental health promotion, or to assess the impact of HRLAs on health inequalities.
      CONCLUSIONS: Overall, there is limited evidence suggesting that HRLAs are cost
      effective in terms of changing health-related knowledge, behaviours or health
      outcomes. The evidence that does exist indicates that HRLAs are only cost
      effective when they target behaviours likely to have a large impact on overall
      health-related quality of life. Further development of HRLA interventions needs
      to target specific population health needs where potential exists for significant
      improvement, and include rigorous evaluation to ensure that HRLAs provide
      sufficient value for money.

PMID- 24304828
TI  - Vaccination coverage among persons with asthma -- United States, 2010-2011
      influenza season.
AB  - Asthma was the most common underlying condition among persons hospitalized with
      pandemic influenza A (H1N1) virus infection in 2009. Although persons with asthma
      are not more likely than others to get influenza, influenza can make asthma
      symptoms worse, trigger asthma attacks, and lead to pneumonia or other
      complications that result in hospitalization and even death. During 1964-2010,
      the Advisory Committee on Immunization Practices (ACIP) recommended that all
      adults and children aged >=6 months with asthma receive an influenza vaccination
      annually. Beginning with the 2010-11 influenza season, ACIP expanded its annual
      vaccination recommendation to include all persons aged >=6 months, while
      emphasizing that protection of persons at higher risk for influenza-related
      complications continue as a focus of vaccination efforts. To provide the first
      update of national vaccination coverage among persons aged >=2 years with asthma
      since the new ACIP recommendation, CDC analyzed data from the 2010 and 2011
      National Health Interview Survey (NHIS). This report describes the results of
      that analysis, which indicated that influenza vaccination during the 2010-11
      season among persons with asthma was 50%, up from 36% 5 years earlier. However,
      vaccination coverage across all age groups, including among those with health
      insurance, a usual place for health care, and one or more health-care visits in
      the past 12 months, remained well below Healthy People 2020 targets of 80% for
      children aged 6 months-17 years and 90% for adults aged >=18 years who are at
      high risk. These findings highlight the need to educate health-care providers and
      persons with asthma about the importance of annual influenza vaccination. 

PMID- 24304829
TI  - Multistate outbreak of salmonella chester infections associated with frozen meals
      -- 18 states, 2010.
AB  - On May 24, 2010, a cluster of 17 human Salmonella enterica serotype Chester
      clinical isolates with indistinguishable pulsed-field gel electrophoresis (PFGE)
      patterns was reported to PulseNet, the national molecular subtyping network for
      foodborne disease surveillance. This PFGE pattern had not been reported
      previously. Subsequently, CDC conducted an investigation that identified 44 ill
      persons in 18 states during May 24-June 19, 2010. In a multistate case-control
      study, consumption of a brand A frozen meal was associated with illness (matched
      odds ratio [mOR] = 30.7; 95% confidence interval [CI] = 6.4-infinity). On June
      17, 2010, the manufacturer (company A) voluntarily recalled its brand A cheesy
      chicken and rice frozen meals. The outbreak strain of Salmonella Chester was
      isolated from eight unopened samples. A root cause analysis conducted by company
      A identified chicken as a possible contaminated ingredient. Many frozen meals are
      not "heat and serve" items but rather are "not-ready-to-eat" (NRTE) products that
      require full cooking before consumption because they might include ingredients
      that have not gone through a pathogen kill-step process. Because Salmonella and
      other pathogens can survive in NRTE products, such products must be fully cooked
      before eating and clearly labeled with instructions for safe handling and
      cooking. 

PMID- 24304830
TI  - Rubella and congenital rubella syndrome control and elimination - global
      progress, 2000-2012.
AB  - Rubella virus usually causes a mild fever and rash in children and adults.
      However, infection during pregnancy, especially during the first trimester, can
      result in miscarriage, stillbirth, or infants with congenital malformations,
      known as congenital rubella syndrome (CRS). In 2011, the World Health
      Organization (WHO) updated guidance on the preferred strategy for introduction of
      rubella-containing vaccine (RCV) into national routine immunization schedules
      with an initial wide-age-range vaccination campaign that includes children aged 9
      months-15 years. WHO also urged all member states to take the opportunity offered
      by accelerated measles control and elimination activities as a platform to
      introduce RCVs. The Global Measles and Rubella Strategic Plan (2012-2020)
      published by the Measles Rubella Initiative partners in 2012 and the Global
      Vaccine Action Plan endorsed by the World Health Assembly in 2012 include
      milestones to eliminate rubella and CRS in two WHO regions by 2015, and eliminate
      rubella in five WHO regions by 2020. This report summarizes the global progress
      of rubella and CRS control and elimination during 2000-2012. As of December 2012,
      a total of 132 (68%) WHO member states had introduced RCV, a 33% increase from 99
      member states in 2000. A total of 94,030 rubella cases were reported to WHO in
      2012 from 174 member states, an 86% decrease from the 670,894 cases reported in
      2000 from 102 member states. The WHO Region of the Americas (AMR) and European
      Region (EUR) have established rubella elimination goals of 2010 and 2015,
      respectively. AMR has started to document the elimination of measles, rubella,
      and CRS; in EUR, rubella incidence has decreased significantly, although
      outbreaks continue to occur. 

PMID- 24304831
TI  - Notes from the field: Escherichia coli O157:H7 outbreak associated with seasonal
      consumption of raw ground beef - Wisconsin, December 2012-January 2013.
AB  - On January 8, 2013, the Wisconsin State Laboratory of Hygiene notified the
      Wisconsin Division of Public Health (WDPH) of two patients with Escherichia coli
      O157:H7 clinical isolates that had indistinguishable, but commonly identified,
      pulsed-field gel electrophoresis (PFGE) patterns. The two patients were
      interviewed by local health departments within 1 day of the initial report. They
      revealed that they had eaten raw ground beef purchased from the same meat market
      and served as "tiger meat" or "cannibal sandwiches." In this dish, the raw ground
      beef typically is served on rye bread or crackers with onions and is a
      traditional winter holiday specialty in certain regions of the upper Midwest.
      Five agencies (the Watertown Department of Health; WDPH; Wisconsin Department of
      Agriculture, Trade, and Consumer Protection; U.S. Department of Agriculture's
      Food Safety and Inspection Service; and CDC) investigated to determine the
      magnitude of the outbreak, prevent additional infections, and better understand
      raw ground beef consumption. 

PMID- 24304832
TI  - Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell
      properties in in vitro culture.
AB  - Several studies have already described the presence of specialized niches of
      precursor cells in vasculature wall, and it has been shown that these populations
      share several features with mesenchymal stromal cells (MSCs). Considering the
      relevance of MSCs in the cardiovascular physiopathology and regenerative
      medicine, and the usefulness of the pig animal model in this field, we reported a
      new method for MSC-like cell isolation from pig aorta. Filling the vessel with a
      collagenase solution for 40 min, all endothelial cells were detached and
      discarded and then collagenase treatment was repeated for 4 h to digest
      approximately one-third of the tunica media. The ability of our method to select
      a population of MSC-like cells from tunica media could be ascribed in part to the
      elimination of contaminant cells from the intimal layer and in part to the
      overnight culture in the high antibiotic/antimycotic condition and to the
      starvation step. Aortic-derived cells show an elongated, spindle shape,
      fibroblast-like morphology, as reported for MSCs, stain positively for CD44,
      CD56, CD90, and CD105; stain negatively for CD34 and CD45; and express CD73 mRNA.
      Moreover, these cells show the classical mesenchymal trilineage differentiation
      potential. Under our in vitro culture conditions, aortic-derived cells share some
      phenotypical features with pericytes and are able to take part in the formation
      of network-like structures if cocultured with human umbilical vein endothelial
      cells. In conclusion, our work reports a simple and highly suitable method for
      obtaining large numbers of precursor MSC-like cells derived from the porcine
      aortic wall. 

PMID- 24304834
TI  - Energy-sensitive regulation of Na+/K+-ATPase by Janus kinase 2.
AB  - Janus kinase 2 (JAK2) contributes to intracellular signaling of leptin and
      erythropoietin, hormones protecting cells during energy depletion. The present
      study explores whether JAK2 is activated by energy depletion and regulates
      Na(+)/K(+)-ATPase, the major energy-consuming pump. In Jurkat cells, JAK2
      activity was determined by radioactive kinase assay, phosphorylated JAK2 detected
      by Western blotting, ATP levels measured by luciferase assay, as well as
      Na(+)/K(+)-ATPase alpha1-subunit transcript and protein abundance determined by
      real-time PCR and Western blotting, respectively. Ouabain-sensitive K(+)-induced
      currents (Ipump) were measured by whole cell patch clamp. Ipump was further
      determined by dual-electrode voltage clamp in Xenopus oocytes injected with cRNA
      encoding JAK2, active (V617F)JAK2, or inactive (K882E)JAK2. As a result, in
      Jurkat T cells, JAK2 activity significantly increased following energy depletion
      by sodium azide (NaN3) or 2,4- dinitro phenol (DNP). DNP- and NaN3-induced
      decrease of cellular ATP was significantly augmented by JAK2 inhibitor AG490 and
      blunted by Na(+)/K(+)-ATPase inhibitor ouabain. DNP decreased and AG490 enhanced
      Ipump as well as Na(+)/K(+)-ATPase alpha1-subunit transcript and protein
      abundance. The alpha1-subunit transcript levels were also enhanced by signal
      transducer and activator of transcription-5 inhibitor CAS 285986-31-4. In Xenopus
      oocytes, Ipump was significantly decreased by expression of JAK2 and (V617F)JAK2
      but not of (K882E)JAK2, effects again reversed by AG490. In (V617F)JAK2
      expressing Xenopus oocytes, neither DNP nor NaN3 resulted in further decline of
      Ipump. In Xenopus oocytes, the effect of (V617F)JAK2 on Ipump was not prevented
      by inhibition of transcription with actinomycin. In conclusion, JAK2 is a novel
      energy-sensing kinase that curtails energy consumption by downregulating
      Na(+)/K(+)-ATPase expression and activity. 

PMID- 24304833
TI  - Mitochondrial 8-oxoguanine glycosylase decreases mitochondrial fragmentation and
      improves mitochondrial function in H9C2 cells under oxidative stress conditions.
AB  - The mitochondrial DNA base modification 8-hydroxy 2'-deoxyguanine (8-OHdG) is one
      of the most common DNA lesions induced by reactive oxygen species (ROS) and is
      considered an index of DNA damage. High levels of mitochondrial 8-OHdG have been
      correlated with increased mutation, deletion, and loss of mitochondrial (mt) DNA,
      as well as apoptosis. 8-Oxoguanosine DNA glycosylase-1 (OGG1) recognizes and
      removes 8-OHdG to prevent further DNA damage. We evaluated the effects of OGG1 on
      mtDNA damage, mitochondrial function, and apoptotic events induced by oxidative
      stress using H9C2 cardiac cells treated with menadione and transduced with either
      Adv-Ogg1 or Adv-Control (empty vector). The levels of mtDNA 8-OHdG and the
      presence of apurinic/apyrimidinic (AP) sites were decreased by 30% and 35%,
      respectively, in Adv-Ogg1 transduced cells (P < 0.0001 and P < 0.005,
      respectively). In addition, the expression of base excision repair (BER) pathway
      members APE1 and DNA polymerase gamma was upregulated by Adv-Ogg1 transduction.
      Cells overexpressing Ogg1 had increased membrane potential (P < 0.05) and
      decreased mitochondrial fragmentation (P < 0.005). The mtDNA content was found to
      be higher in cells with increased OGG1 (P < 0.005). The protein levels of fission
      and apoptotic factors such as DRP1, FIS1, cytoplasmic cytochrome c, activated
      caspase-3, and activated caspase-9 were lower in Adv-Ogg1 transduced cells. These
      observations suggest that Ogg1 overexpression may be an important mechanism to
      protect cardiac cells against oxidative stress damage. 

PMID- 24304835
TI  - Fiber hypertrophy and increased oxidative capacity can occur simultaneously in
      pig glycolytic skeletal muscle.
AB  - An inverse relationship between skeletal muscle fiber cross-sectional area (CSA)
      and oxidative capacity suggests that muscle fibers hypertrophy at the expense of
      oxidative capacity. Therefore, our objective was to utilize pigs possessing
      mutations associated with increased oxidative capacity [AMP-activated protein
      kinase (AMPKgamma3(R200Q))] or fiber hypertrophy [ryanodine receptor 1
      (RyR1(R615C))] to determine if these events occur in parallel. Longissimus muscle
      was collected from wild-type (control), AMPKgamma3(R200Q), RyR1(R615C), and
      AMPKgamma3(R200Q)-RyR1(R615C) pigs. Regardless of AMPK genotype, RyR(R615C)
      increased fiber CSA by 35%. In contrast, AMPKgamma3(R200Q) pig muscle exhibited
      greater citrate synthase and beta-hydroxyacyl CoA dehydrogenase activity.
      Isolated mitochondria from AMPKgamma3(R200Q) muscle had greater maximal, ADP
      stimulated oxygen consumption rate. Additionally, AMPKgamma3(R200Q) muscle
      contained more (~50%) of the mitochondrial proteins succinate dehydrogenase and
      cytochrome c oxidase and more mitochondrial DNA. Surprisingly, RyR1(R615C)
      increased mitochondrial proteins and DNA, but this was not associated with
      improved oxidative capacity, suggesting that altered energy metabolism in
      RyR1(R615C) muscle influences mitochondrial proliferation and protein turnover.
      Thus pigs that possess both AMPKgamma3(R200Q) and RyR(R615C) exhibit increased
      muscle fiber CSA as well as greater oxidative capacity. Together, our findings
      support the notion that hypertrophy and enhanced oxidative capacity can occur
      simultaneously in skeletal muscle and suggest that the signaling mechanisms
      controlling these events are independently regulated. 

PMID- 24304836
TI  - Functional properties of human ferroportin, a cellular iron exporter reactive
      also with cobalt and zinc.
AB  - Iron homeostasis is achieved by regulating the intestinal absorption of the metal
      and its recycling by macrophages. Iron export from enterocytes or macrophages to
      blood plasma is thought to be mediated by ferroportin under the control of
      hepcidin. Although ferroportin was identified over a decade ago, little is
      understood about how it works. We expressed in Xenopus oocytes a human
      ferroportin-enhanced green fluorescent protein fusion protein and observed using
      confocal microscopy its exclusive plasma-membrane localization. As a first step
      in its characterization, we established an assay to detect functional expression
      of ferroportin by microinjecting oocytes with (55)Fe and measuring efflux.
      Ferroportin expression increased the first-order rate constants describing (55)Fe
      efflux up to 300-fold over control. Ferroportin-mediated (55)Fe efflux was
      saturable, temperature-dependent (activation energy, Ea ~ 17 kcal/mol), maximal
      at extracellular pH ~ 7.5, and inactivated at extracellular pH < 6.0. We
      estimated that ferroportin reacts with iron at its intracellular aspect with
      apparent affinity constant < 10(-7) M. Ferroportin expression also stimulated
      efflux of (65)Zn and (57)Co but not of (64)Cu, (109)Cd, or (54)Mn. Hepcidin
      treatment of oocytes inhibited efflux of (55)Fe, (65)Zn, and (57)Co. Whereas
      hepcidin administration in mice resulted in a marked hypoferremia within 4 h, we
      observed no effect on serum zinc levels in those same animals. We conclude that
      ferroportin is an iron-preferring cellular metal-efflux transporter with a narrow
      substrate profile that includes cobalt and zinc. Whereas hepcidin strongly
      regulated serum iron levels in the mouse, we found no evidence that ferroportin
      plays an important role in zinc homeostasis. 

PMID- 24304837
TI  - Using mixed methods to investigate factors influencing reporting of livestock
      diseases: a case study among smallholders in Bolivia.
AB  - Livestock disease surveillance is particularly challenging in resource-scarce
      settings, where disease events are often unreported. Surveillance performance is
      determined as much by the quantifiable biological attributes of the disease, as
      it is by motivations and barriers perceived by livestock keepers for disease
      reporting. Mixed methods designs, which integrate the collection, analysis and
      interpretation of qualitative and quantitative data in a single study, are
      increasingly used across different disciplines. These designs allow for a deeper
      exploration of the topic under investigation, than can be achieved by either
      approach alone. In this study a mixed methods design was used in order to gain a
      greater understanding of the factors that influence reporting of livestock
      diseases in Bolivia. There is a need to strengthen passive surveillance in this
      country, among other reasons as part of an eradication programme for Foot and
      Mouth Disease (FMD). Findings revealed livestock keepers in the study area were
      extremely unlikely to report the occurrence of livestock health events to the
      Official Veterinary Services (OVS). Communication outside the local community
      occurs more often through alternative routes and this is positively correlated
      with disease awareness. The main barriers to disease reporting identified were a
      lack of institutional credibility and the conflicting priorities of the OVS and
      livestock keepers. As for other animal and human diseases across the developing
      world, passive surveillance of livestock diseases in Bolivia should be enhanced;
      this is urgent in view of the current FMD eradication programme. Increasing
      timeliness and smallholders' participation requires a detailed understanding of
      their likely actions and perceived barriers towards disease reporting. These
      insights are most likely to be developed through a holistic mixed methods
      approach of quantitative and qualitative analyses. 

PMID- 24304839
TI  - Spontaneous pneumothorax associated with Aspergillus bronchopneumonia in a dog.
AB  - OBJECTIVE: To describe a case of pulmonary aspergillosis in a previously healthy
      dog that manifested as a spontaneous pneumothorax. CASE SUMMARY: A 3-year-old
      neutered male mixed-breed dog was presented with inappetence and respiratory
      distress. Thoracic radiography revealed a right-sided pneumothorax. Following
      stabilization, thoracic computed tomography found 1 large and many small
      pulmonary blebs in the right caudal lung lobe. The dog underwent a right lateral
      thoracotomy, identifying numerous emphysematous regions in the right middle lung
      lobe, and a right middle lung lobectomy was performed. Histopathologic
      examination of the resected lung lobe revealed severe, diffuse bronchopneumonia
      with necrotizing pleuritis and the presence of fungal organisms strongly
      suggestive of Aspergillus sp. Surgical removal of the affected lung lobe and
      continued medical treatment with itraconazole resolved the dog's clinical signs.
      NEW INFORMATION PROVIDED: This report describes the successful surgical and
      medical management of Aspergillus bronchopneumonia in a dog presenting with
      spontaneous pneumothorax.

PMID- 24304838
TI  - PACE-UP (Pedometer and consultation evaluation--UP)--a pedometer-based walking
      intervention with and without practice nurse support in primary care patients
      aged 45-75 years: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Most adults do not achieve the 150 minutes weekly of at least
      moderate intensity activity recommended for health. Adults' most common physical
      activity (PA) is walking, light intensity if strolling, moderate if brisker.
      Pedometers can increase walking; however, most trials have been short-term, have
      combined pedometer and support effects, and have not reported PA intensity. This
      trial will investigate whether pedometers, with or without nurse support, can
      help less active 45-75 year olds to increase their PA over 12 months.
      METHODS/DESIGN:  DESIGN: Primary care-based 3-arm randomized controlled trial
      with 12-month follow-up and health economic and qualitative evaluations.
      PARTICIPANTS: Less active 45-75 year olds (n = 993) will be recruited by post
      from six South West London general practices, maximum of two per household and
      households randomised into three groups. Step-count and time spent at different
      PA intensities will be assessed for 7 days at baseline, 3 and 12 months by
      accelerometer. Questionnaires and anthropometric assessments will be completed.
      INTERVENTION: The pedometer-alone group will be posted a pedometer (Yamax Digi
      Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking
      programme, using targets from their baseline assessment. The pedometer-plus
      support group will additionally receive three practice nurse PA consultations.
      The handbook, diary and consultations include behaviour change techniques (e.g.,
      self-monitoring, goal-setting, relapse prevention planning). The control group
      will receive usual care. OUTCOMES: Changes in average daily step-count (primary
      outcome), time spent sedentary and in at least moderate intensity PA weekly at 12
      months, measured by accelerometry. Other outcomes include change in body mass
      index, body fat, self-reported PA, quality of life, mood and adverse events. Cost
      effectiveness will be assessed by the incremental cost of the intervention to the
      National Health Service and incremental cost per change in step-count and per
      quality adjusted life year. Qualitative evaluations will explore reasons for
      trial non-participation and the interventions' acceptability. DISCUSSION: The
      PACE-UP trial will determine the effectiveness and cost-effectiveness of a
      pedometer-based walking intervention delivered by post or practice nurse to less
      active primary care patients aged 45-75 years old. Approaches to minimise bias
      and challenges anticipated in delivery will be discussed. TRIAL REGISTRATION:
      ISRCTN98538934.

PMID- 24304840
TI  - Status epilepticus attributed to inadvertent intrathecal injection of cefazolin
      during myelography.
AB  - OBJECTIVE: To describe a case of status epilepticus believed to be a consequence
      of inadvertent intrathecal administration of cefazolin in a dog undergoing a
      myelogram. CASE SUMMARY: A 4-year-old, 6.5 kg, male neutered Dachshund was
      referred for evaluation of an acute onset hind limb paraparesis. While performing
      a lumbar myelogram, cefazolin was inadvertently injected into the ventral
      subarachnoid space. Subsequent refractory seizure activity was attributed to the
      epileptogenic effects of intrathecally administered cefazolin. Supportive therapy
      led to eventual complete recovery. NEW OR UNIQUE INFORMATION PROVIDED: Although
      epileptogenic effects of intrathecally administered cefazolin are well documented
      in the human and experimental animal model literature, to the authors' knowledge
      this has not been characterized in the veterinary literature. This case
      highlights the need to be diligent and mindful when one administers medications,
      and describes the management of a dog adversely affected as a consequence of a
      medical error.

PMID- 24304841
TI  - Acquired Gerbode defect and third-degree atrioventricular block secondary to
      vehicular trauma in a dog.
AB  - OBJECTIVE: To describe a case of traumatically acquired left ventricular to right
      atrial communication (Gerbode defect), atrial septal defect (ASD), and third
      degree atrioventricular block (AVB) necessitating permanent pacemaker placement
      in a dog. CASE SUMMARY: A 1.5-year-old neutered male Newfoundland dog was struck
      by a car and was referred for further evaluation and treatment of hemoabdomen.
      Persistent third-degree AVB, a right-sided cardiac murmur and right-sided
      congestive heart failure (CHF) were identified, and echocardiographic examination
      revealed a type-A Gerbode defect and ASD. Pimobendan, furosemide, and enalapril
      therapies were initiated for treatment of CHF. Persistent AVB eventually
      necessitated permanent pacemaker implantation. Initial attempts at minimally
      invasive occlusion of the Gerbode defect were unsuccessful; however the dog
      continues to do well clinically on chronic cardiac medications. NEW OR UNIQUE
      INFORMATION PROVIDED: To our knowledge, an acquired Gerbode defect secondary to
      trauma with associated ASD, CHF, and third-degree AVB necessitating permanent
      pacemaker therapy have not yet been reported in the veterinary literature. The
      extended survival and follow-up available on this patient postpacemaker
      implantation also documents that longer term survival is possible with this
      defect.

PMID- 24304842
TI  - Presumptive immune-mediated thrombocytopenia secondary to massive Africanized bee
      envenomation in a dog.
AB  - OBJECTIVE: To describe a case of immune-mediated thrombocytopenia (IMT) after
      massive Africanized bee envenomation in a dog. CASE SUMMARY: While boarding at a
      kennel, a dog was stung by approximately 300 Africanized bees. During initial
      veterinary examination, the dog was deemed to be in shock, characterized by
      collapse, with hypotension, bradycardia, and hypoglycemia. In addition, severe
      diffuse erythema and edema were noted over the entire body. Supportive care,
      including IV crystalloid and colloid fluids, dextrose, fresh frozen plasma,
      oxygen therapy, broad spectrum antimicrobials, dexamethasone, and diphenhydramine
      was initiated. The dog's condition stabilized over the next 2 days. Forty-eight
      hours after admission the dog developed hematemesis and hematochezia, and severe
      thrombocytopenia was identified. Extensive diagnostic investigation revealed no
      likely trigger other than the Africianized bee exposure, and a diagnosis of IMT
      was made. Following a red blood cell transfusion and immunosuppressive doses of
      dexamethasone and gastroprotectant therapy, the dog's condition stabilized, and
      the platelet count returned to normal after 7 days from initiation of therapy.
      NEW OR UNIQUE INFORMATION PROVIDED: IMT is a possible sequelae of massive
      Africanized bee envenomation in the dog.

PMID- 24304843
TI  - Successful cardiopulmonary resuscitation following cardiopulmonary arrest in a
      geriatric chinchilla.
AB  - OBJECTIVE: To describe the successful application of CPR in a geriatric
      chinchilla employing basic and advanced life support measures during
      cardiopulmonary arrest (CPA). CASE SUMMARY: A 13-year-old female intact
      chinchilla presented to a general and multispecialty referral hospital for a
      dental procedure. During recovery from anesthesia the patient suffered CPA and
      CPR was initiated. Noninvasive positive pressure mask ventilation was initiated
      and external chest compressions were performed. An 18-Ga needle was introduced
      into the medullary cavity of the right humerus as an intraosseous catheter and
      provided access for administration of drugs and fluids. After return of
      spontaneous circulation was noted mannitol was administered via the intraosseous
      catheter to alleviate suspected increased intracranial pressure. Clinical
      improvement was noted shortly after administration. Monitoring during the
      recovery period showed a normal sinus cardiac rhythm and a SpO2 of 100% while on
      supplemental oxygen. Neurologic function continued to improve over the following
      hours. Oxygen therapy was provided via an oxygen cage, and administration of
      antimicirobials, gastrointestinal protectants, and nutritional supplementation
      were part of the post resuscitation care. Oxygen therapy was discontinued after
      24 hours, during which time normal behaviors were observed and neurologic status
      was considered appropriate. The patient was discharged 48 hours after CPA. NEW OR
      UNIQUE INFORMATION PROVIDED: Published reports from clinical practice on the
      outcomes of CPR for exotic small mammals are limited. This report details the
      successful outcome of the use of combined basic and advanced life support
      measures for the provision of CPR in a chinchilla. This report also highlights
      the utility of an intraosseous catheter for administration of drugs and fluids
      novel to this species during resuscitation and recovery. To the authors'
      knowledge this is the first published report of successful CPR following CPA in a
      geriatric chinchilla.

PMID- 24304854
TI  - Child uptake of smoking by area across the UK.
AB  - Smoking is a major public health problem. As smokers age and die prematurely, the
      tobacco industry must continue to recruit new, young smokers. Survey data
      indicate that currently in the UK around 207,000 children aged 11-15 start
      smoking every year. We used local data on adult smoking rates to apportion
      national data on child smoking uptake to specific areas. The presentation of data
      for individual local authorities, which now have responsibility for public
      health, can be used to focus attention locally. For example, this analysis
      demonstrates that each day, 67 children, more than two classrooms full, start
      smoking in London.

PMID- 24304855
TI  - Specific loop modifications of the thrombin-binding aptamer trigger the formation
      of parallel structures.
AB  - Guanine-rich sequences show large structural variability, with folds ranging from
      duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can
      show multiple stoichiometries, parallel and antiparallel strand alignments, and
      different topological arrangements. We analyze here the equilibrium between
      intramolecular antiparallel and intermolecular parallel G-quadruplexes in the
      thrombin-binding aptamer (TBA) sequence. Our theoretical and experimental studies
      demonstrate that an apparently simple modification at the loops of TBA induces a
      large change in the monomeric antiparallel structure of TBA to yield a parallel G
      quadruplex showing a novel T-tetrad. The present results illustrate the extreme
      polymorphism of G-quadruplexes and the ease with which their conformation in
      solution can be manipulated by nucleotide modification. 

PMID- 24304856
TI  - Dynamics of tissue topology during cancer invasion and metastasis.
AB  - During tumor progression, cancer cells mix with other cell populations including
      epithelial and endothelial cells. Although potentially important clinically as
      well as for our understanding of basic tumor biology, the process of mixing is
      largely a mystery. Furthermore, there is no rigorous, analytical measure
      available for quantifying the mixing of compartments within a tumor. I present
      here a mathematical model of tissue repair and tumor growth based on collective
      cell migration that simulates a wide range of observed tumor behaviors with
      correct tissue compartmentalization and connectivity. The resulting dynamics are
      analyzed in light of the Euler characteristic number (chi), which describes key
      topological features such as fragmentation, looping and cavities. The analysis
      predicts a number of regimes in which the cancer cells can encapsulate normal
      tissue, form a co-interdigitating mass, or become fragmented and encapsulated by
      endothelial or epithelial structures. Key processes that affect the topological
      changes are the production of provisional matrix in the tumor, and the migration
      of endothelial or epithelial cells on this matrix. Furthermore, the simulations
      predict that topological changes during tumor invasion into blood vessels may
      contribute to metastasis. The topological analysis outlined here could be useful
      for tumor diagnosis or monitoring response to therapy and would only require high
      resolution, 3D image data to resolve and track the various cell compartments. 

PMID- 24304857
TI  - A prospective study of statin use and poststroke depression.
AB  - Associations between serum cholesterol levels or lipid-lowering treatment and
      depression risk have been controversial. Associations between statin use and
      depression risk have been investigated in patients with coronary artery diseases
      but have not been examined after stroke. This study aimed to investigate whether
      statin use was associated with depression ascertained at 2 weeks and 1 year after
      stroke. A total of 423 patients were evaluated 2 weeks after stroke, and 288
      (68%) were followed 1 year later. At the 2 examinations, depression (major or
      minor depressive disorder) was diagnosed according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition criteria, and depression
      severity was assessed by the Hospital Anxiety and Depression Scale-Depression
      subscale and the Hamilton Depression Rating Scale. Logistic regression and
      repeated-measures analyses of variance were carried out. Statins were used in 251
      (59%) of 423 patients at baseline. Statin use was not associated with poststroke
      depression (PSD) status at baseline but was significantly associated with reduced
      risk of all PSD, and of major PSD specifically, at follow-up. Statin use was also
      associated with better trajectories of depression assessment scale scores over
      the 1-year follow-up. Statin use was associated with a reduced risk of depression
      at 1 year after stroke. Likely causality and underlying mechanisms need to be
      further clarified. 

PMID- 24304858
TI  - An open-label, pilot study evaluating the safety and antidepressant effects of
      Rellidep in major depressive disorder.
AB  - BACKGROUND: In 4 clinical studies of a biological tissue isolate (BTI) similar to
      Rellidep, the majority of subjects reported improved well-being and mood. Based
      on these reports of positive effect on mood in trials, an antidepressant pilot
      study was undertaken with the BTI Rellidep. METHOD: Twenty-three subjects (14
      women and 9 men; mean age, 44.8 years) with major depressive disorder entered an
      8-week trial of Rellidep with a 17-item Hamilton Depression Rating Scale (HAM-D)
      score of 18 or above. Three subjects dropped out before beginning treatment,
      leaving an intention-to-treat (ITT) sample of 20. Sixteen subjects completed the
      trial. All patients received Rellidep 1000 mg (500 mg * 2) twice a day orally
      daily for 8 weeks. No other treatments were permitted except for intermittent
      lorazepam for sleep if necessary. The primary response to treatment outcome was a
      50% decline on the HAM-D. Secondary measures included the Beck Depression
      Inventory, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression,
      Hamilton Rating Scale for Anxiety, Medical Outcomes Study Short-Form 36, and
      Arizona Sexual Experience Scale. RESULTS: The overall response rate was 75%
      (15/20). Almost 87% of those who responded did so by week 4. The data analysis of
      change scores indicates that for the ITT population the decrease in the HAM-D was
      statistically significant (P < 0.001). On all other measures, improvement from
      baseline was statistically significant (P < 0.001), except for the Arizona Sexual
      Experience Scale (ITT: P = 0.055). There were no significant adverse events.
      CONCLUSIONS: The positive outcome of this open trial indicates that Rellidep may
      be an effective and safe antidepressant. Further placebo-controlled trials are
      indicated.

PMID- 24304859
TI  - Ongoing activity in the optic tectum is correlated on a trial-by-trial basis with
      the pupil dilation response.
AB  - The selection of the appropriate stimulus to induce an orienting response is a
      basic task thought to be partly achieved by tectal circuitry. Here we addressed
      the relationship between neural activity in the optic tectum (OT) and orienting
      behavioral responses. We recorded multiunit activity in the intermediate/deep
      layers of the OT of the barn owl simultaneously with pupil dilation responses
      (PDR, a well-known orienting response common to birds and mammals). A trial-by
      trial analysis of the responses revealed that the PDR generally did not correlate
      with the evoked neural responses but significantly correlated with the rate of
      ongoing neural activity measured shortly before the stimulus. Following this
      finding, we characterized ongoing activity in the OT and showed that in the
      intermediate/deep layers it tended to fluctuate spontaneously. It is
      characterized by short periods of high ongoing activity during which the
      probability of a PDR to an auditory stimulus inside the receptive field is
      increased. These high-ongoing activity periods were correlated with increase in
      the power of gamma band local field potential oscillations. Through dual
      recordings, we showed that the correlation coefficients of ongoing activity
      decreased as a function of distance between recording sites in the tectal map.
      Significant correlations were also found between recording sites in the OT and
      the forebrain entopallium. Our results suggest that an increase of ongoing
      activity in the OT reflects an internal state during which coupling between
      sensory stimulation and behavioral responses increases. 

PMID- 24304860
TI  - Synchronized firing of fast-spiking interneurons is critical to maintain balanced
      firing between direct and indirect pathway neurons of the striatum.
AB  - The inhibitory circuits of the striatum are known to be critical for motor
      function, yet their contributions to Parkinsonian motor deficits are not clear.
      Altered firing in the globus pallidus suggests that striatal medium spiny neurons
      (MSN) of the direct (D1 MSN) and indirect pathway (D2 MSN) are imbalanced during
      dopamine depletion. Both MSN classes receive inhibitory input from each other and
      from inhibitory interneurons within the striatum, specifically the fast-spiking
      interneurons (FSI). To investigate the role of inhibition in maintaining striatal
      balance, we developed a biologically-realistic striatal network model consisting
      of multicompartmental neuron models: 500 D1 MSNs, 500 D2 MSNs and 49 FSIs. The D1
      and D2 MSN models are differentiated based on published experiments of individual
      channel modulations by dopamine, with D2 MSNs being more excitable than D1 MSNs.
      Despite this difference in response to current injection, in the network D1 and
      D2 MSNs fire at similar frequencies in response to excitatory synaptic input.
      Simulations further reveal that inhibition from FSIs connected by gap junctions
      is critical to produce balanced firing. Although gap junctions produce only a
      small increase in synchronization between FSIs, removing these connections
      resulted in significant firing differences between D1 and D2 MSNs, and balanced
      firing was restored by providing synchronized cortical input to the FSIs.
      Together these findings suggest that desynchronization of FSI firing is
      sufficient to alter balanced firing between D1 and D2 MSNs. 

PMID- 24304861
TI  - The mechanical actions of muscles predict the direction of muscle activation
      during postural perturbations in the cat hindlimb.
AB  - Humans and cats respond to balance challenges, delivered via horizontal support
      surface perturbations, with directionally selective muscle recruitment and
      constrained ground reaction forces. It has been suggested that this postural
      strategy arises from an interaction of limb biomechanics and proprioceptive
      networks in the spinal cord. A critical experimental validation of this
      hypothesis is to test the prediction that the principal directions of muscular
      activation oppose the directions responding muscles exert their forces on the
      environment. Therefore, our objective was to quantify the endpoint forces of a
      diverse set of cat hindlimb muscles and compare them with the directionally
      sensitive muscle activation patterns generated in the intact and decerebrate cat.
      We hypothesized that muscles are activated based on their mechanical advantage.
      Our primary expectation was that the principal direction of muscle activation
      during postural perturbations will be directed oppositely (180 degrees ) from the
      muscle endpoint ground reaction force. We found that muscle activation during
      postural perturbations was indeed directed oppositely to the endpoint reaction
      forces of that muscle. These observations indicate that muscle recruitment during
      balance challenges is driven, at least in part, by limb architecture. This
      suggests that sensory sources that provide feedback about the mechanical
      environment of the limb are likely important to appropriate and effective
      responses during balance challenges. Finally, we extended the analysis to three
      dimensions and different stance widths, laying the groundwork for a more
      comprehensive study of postural regulation than was possible with measurements
      confined to the horizontal plane and a single stance configuration. 

PMID- 24304862
TI  - Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses
      and rostral ventromedial medulla cell activity in neuropathic pain conditions.
AB  - The present study investigated the role of metabotropic glutamate receptor
      subtype 8 (mGluR8) in the dorsal striatum (DS) in modulating thermonociception
      and rostral ventromedial medulla (RVM) ON and OFF cell activities in conditions
      of neuropathic pain induced by spared nerve injury (SNI) of the sciatic nerve in
      rats. The role of DS mGluR8 on mechanical allodynia was also investigated. Intra
      DS (S)-3,4-dicarboxyphenylglycine [(S)-3,4-DCPG], a selective mGluR8 agonist, did
      not modify the activity of the ON and OFF cells in sham-operated rats. In SNI
      rats, which showed a reduction of the mechanical withdrawal threshold, intra-DS
      microinjection of (S)-3,4-DCPG inhibited the ongoing and tail flick-evoked
      activity of the ON cells while increasing the activity of the OFF cells.
      AZ12216052, a selective mGluR8 positive allosteric modulator (PAM), behaved like
      (S)-3,4-DCPG in increasing tail flick latency and OFF cell activity and
      decreasing ON cell activity in SNI rats only but was less potent. VU0155041, a
      selective mGluR4 PAM, was ineffective in changing thermal nociception and ON and
      OFF cell activity in both sham-operated and SNI rats. (S)-3,4-DCPG did not change
      mechanical withdrawal threshold in sham-operated rats but increased it in SNI
      rats. Furthermore, a decreased level of mGluR8 gene and immunoreactivity,
      expressed on GABAergic terminals, associated with a protein increase was found in
      the DS of SNI rats. These results suggest that stimulation of mGluR8 inhibits
      thermoceptive responses and mechanical allodynia. These effects were associated
      with inhibition of ON cells and stimulation of OFF cells within RVM. 

PMID- 24304863
TI  - Adaptation to Coriolis perturbations of voluntary body sway transfers to
      preprogrammed fall-recovery behavior.
AB  - In a rotating environment, goal-oriented voluntary movements are initially
      disrupted in trajectory and endpoint, due to movement-contingent Coriolis forces,
      but accuracy is regained with additional movements. We studied whether adaptation
      acquired in a voluntary, goal-oriented postural swaying task performed during
      constant-velocity counterclockwise rotation (10 RPM) carries over to recovery
      from falling induced using a hold and release (H&R) paradigm. In H&R, standing
      subjects actively resist a force applied to their chest, which when suddenly
      released results in a forward fall and activation of an automatic postural
      correction. We tested H&R postural recovery in subjects (n = 11) before and after
      they made voluntary fore-aft swaying movements during 20 trials of 25 s each, in
      a counterclockwise rotating room. Their voluntary sway about their ankles
      generated Coriolis forces that initially induced clockwise deviations of the
      intended body sway paths, but fore-aft sway was gradually restored over
      successive per-rotation trials, and a counterclockwise aftereffect occurred
      during postrotation attempts to sway fore-aft. In H&R trials, we examined the
      initial 10- to 150-ms periods of movement after release from the hold force, when
      voluntary corrections of movement path are not possible. Prerotation subjects
      fell directly forward, whereas postrotation their forward motion was deviated
      significantly counterclockwise. The postrotation deviations were in a direction
      consistent with an aftereffect reflecting persistence of a compensation acquired
      per-rotation for voluntary swaying movements. These findings show that control
      and adaptation mechanisms adjusting voluntary postural sway to the demands of a
      new force environment also influence the automatic recovery of posture. 

PMID- 24304864
TI  - Update on minimally invasive hemodynamic monitoring in thoracic anesthesia.
AB  - PURPOSE OF REVIEW: Advanced hemodynamic monitoring is indispensable for adequate
      management of patients undergoing major surgery. This article will summarize
      minimally invasive hemodynamic monitoring technologies and their potential use in
      thoracic anesthesia. RECENT FINDINGS: According to their inherent principle,
      currently available technologies can be classified into four groups: bioimpedance
      and bioreactance, applied Fick's principle, pulse wave analysis and Doppler. All
      devices measure stroke volume and cardiac output. Functional hemodynamic
      variables and volumetric parameters have been integrated in some devices. Two
      major indications can be identified: the 'hemodynamically unstable' patient and
      the patient 'at risk' for hemodynamic instability. Although there is evidence for
      the first indication, pre-emptive hemodynamic therapy or perioperative
      hemodynamic optimization for the patient 'at risk' is still an issue of ongoing
      debate. There is a growing body of evidence that this approach can positively
      influence patients' outcome with less postoperative complications in selected
      patient groups. SUMMARY: Many different minimally invasive hemodynamic monitoring
      devices have been developed and clinically introduced in the last years. They
      offer the advantage of being less invasive and easier to use. However, these
      techniques have several limitations and data are scarce in patients undergoing
      thoracic anesthesia, preventing their widespread use so far.

PMID- 24304865
TI  - Intra- and interobserver variability of language mapping by navigated
      transcranial magnetic brain stimulation.
AB  - BACKGROUND: Repetitive navigated transcranial magnetic stimulation (rTMS) has
      been used for studying language organization in healthy volunteers and patients,
      and to detect cortical areas involved in language processing. However, little is
      known about the reliability of this method. To determine the reliability of rTMS
      language mapping, we conducted both an interobserver and an intraobserver
      investigation. METHODS: Ten right-handed healthy subjects underwent language
      mapping by rTMS and the same object-naming task three times. Intraobserver and
      interobserver reliability of seven different error types were tested by two
      investigators. Analysis was performed blinded to the previous results and
      stimulated cortical sites. RESULTS: Overall, the results of both the
      interobserver and the intraobserver investigations show variable accordance. This
      is demonstrated by comparing the error rates of all different error types of the
      three examinations. Considering the most important error type, "no response",
      there is only small variability in inter- and intraobserver mapping. CONCLUSIONS:
      With our current protocol, interobserver and intraobserver comparisons only
      corresponded partially. Thus, although rTMS seems a promising method for
      preoperative planning as well as neuropsychological research, the current
      protocol needs further improvement.

PMID- 24304866
TI  - Neural connectivity of the anterior body of the fornix in the human brain:
      diffusion tensor imaging study.
AB  - A few studies have reported on the neural connectivity of the fornix in the human
      brain, however, little is known about the neural connectivity of the anterior
      body of the fornix. In this study, we used diffusion tensor imaging in
      investigation of the neural connectivity of the anterior body of the fornix in
      normal subjects. Forty healthy subjects were recruited for this study. A seed
      region of interest was placed on the anterior body of the fornix using the FMRIB
      Software Library. Connectivity was defined as the incidence of connection between
      the anterior body of the fornix and any neural structure of the brain at the
      threshold of 5, 25, and 50 streamlines. In all subjects, the anterior body of the
      fornix showed 100% connectivity to the anterior commissure and hypothalamus at
      thresholds of 5, 25, and 50. On the other hand, regarding the thresholds of 5,
      25, and 50, the anterior body of the fornix showed connectivity to the septal
      forebrain region (53.8, 23.8, and 15.0%), frontal lobe via anterior commissure
      (41.3,12.5, and 10.0%), medial temporal lobe (85.0,66.3, and 62.5%), lateral
      temporal lobe (75.0, 56.3, and 35.0%), occipital lobe (21.3, 5.0, and 1.3%),
      frontal lobe via septum pellucidum (28.8, 13.8, and 8.8%), tegmentum of midbrain
      (7.5, 5.0, and 0%), tectum of midbrain (2.5,0, and 0%), and tegmentum of pons
      (5.0,0, and 0%). The anterior body of the fornix showed high connectivity with
      the anterior commissure and hypothalamus, and brain areas relevant to cholinergic
      nuclei (the septal forebrain region and brainstem) and memory function (the
      medial temporal lobe). 

PMID- 24304867
TI  - NAD(+) treatment prevents rotenone-induced apoptosis and necrosis of
      differentiated PC12 cells.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) plays critical roles in not only
      energy metabolism and mitochondrial functions, but also calcium homeostasis and
      immunological functions. It has been reported that NAD(+) administration can
      reduce ischemic brain damage. However, the mechanisms underlying the protective
      effects remain unclear. Because mitochondrial impairments play a key role in the
      cell death in cerebral ischemia, in this study we tested our hypothesis that
      NAD(+) can decrease mitochondrial damage-induced cell death using differentiated
      PC12 cells as a cellular model. We found that NAD(+) can decrease both early
      stage and late-stage apoptosis, as well as necrosis of rotenone-treated PC12
      cells, as assessed by FACS-based Annexin V/AAD assay. We also found that NAD(+)
      treatment can restore the intracellular NAD(+) levels of the rotenone-treated
      cells. Moreover, NAD(+) treatment can prevent rotenone-induced mitochondria
      depolarization. In summary, our study has provided first direct evidence that
      NAD(+) treatment can prevent rotenone-induced apoptosis and necrosis. Our study
      has also indicated that NAD(+) treatment can prevent mitochondrial damage-induced
      cell death, which may at least partially result from its protective effects on
      rotenone-induced mitochondrial depolarization. Because both mitochondrial damage
      and apoptosis play key roles in multiple neurological disorders, our study has
      highlighted the therapeutic potential of NAD(+) for brain ischemia and other
      neurological diseases. 

PMID- 24304868
TI  - Association of RAGE gene polymorphisms with sporadic Parkinson's disease in
      Chinese Han population.
AB  - Previous studies have corroborated receptor for advanced glycation end-products
      (RAGE) ablation had a protective effect on nigral dopaminergic neurons in the
      MPTP model of Parkinson's disease (PD). Genetic variation of RAGE gene may be
      associated with the development of onset of sporadic PD. The present study aimed
      to explore the possible association of RAGE gene polymorphisms namely -374T/A,
      429T/C, and G82S with PD. A total of 285 PD patients and 285 healthy-matched
      individuals in Chinese Han population were enrolled. Genotype analyses were
      performed using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Only the -429T/C polymorphism denoted a significant
      difference between PD patients and controls (P=0.015) of the three examined
      single nucleotide polymorphisms (SNPs). Our data also revealed that -429C allele
      carriers seem to have a decreased risk of PD (OR=0.617, P=0.007). Moreover, there
      were significant differences in genotype distribution in female PD group and its
      healthy-matched control subgroup (P=0.014), as well as between late-onset PD
      (LOPD) and the controls subgroup (P=0.016). However, for -374T/A and 82GS
      polymorphisms, there was no significant difference in the genotype and allele
      frequencies between PD patients and the controls, as well as gender- and age
      related differences. Our present findings indicate that the RAGE -429T/C
      polymorphism may be associated with the susceptibility of PD and the CC genotype
      of -429T/C may be a protective factor for PD in Chinese Han population. 

PMID- 24304869
TI  - Dopamine inhibits neurons from the rat dorsal subcoeruleus nucleus through the
      activation of alpha2-adrenergic receptors.
AB  - Previous studies have revealed that the central dopaminergic system may
      participate in regulating sleep/wakefulness. In particular, rapid eye movement
      (REM) sleep behavior disorder (RBD) occurs in patients with Parkinson's disease
      (PD), highlighting the possible connection between dopamine and REM sleep-related
      neural structures. The dorsal subcoeruleus nucleus (SubCD) is a critical
      structure for the generation and maintenance of REM sleep. Thus, the present
      study investigated the modulatory effects of dopamine on SubCD neurons. Using
      whole-cell patch clamp recordings, we first observed that dopamine induced a
      hyperpolarization of the membrane potentials in SubCD neurons and thus inhibited
      their firing. We determined that a dose-dependent and tetrodotoxin-resistant
      postsynaptic outward current underpinned this inhibitory effect on SubCD neurons
      induced by dopamine. Finally, using pharmacological agents, we revealed that the
      dopamine-elicited outward current in SubCD neurons was mediated by alpha2
      adrenergic receptors, but not by the dopamine receptors, including D1-like and D2
      like receptors. These results suggest that the central dopaminergic system may
      play a role in the regulation of REM sleep through the effect of dopamine on
      SubCD neurons. The relationship between the loss of this effect and the RBD in PD
      is discussed. 

PMID- 24304870
TI  - Assessment of intelligibility using children's spontaneous speech: methodological
      aspects.
AB  - BACKGROUND: Intelligibility is a speaker's ability to convey a message to a
      listener. Including an assessment of intelligibility is essential in both
      research and clinical work relating to individuals with communication disorders
      due to speech impairment. Assessment of the intelligibility of spontaneous speech
      can be used as an overall indicator of the severity of a speech disorder. There
      is a lack of methods for measuring intelligibility on the basis of spontaneous
      speech. AIMS: To investigate the validity and reliability of a method where
      listeners transcribe understandable words and an intelligibility score is
      calculated on the basis of the percentage of syllables perceived as understood.
      METHODS & PROCEDURES: Spontaneous speech from ten children with speech-sound
      disorders (mean age = 6.0 years) and ten children with typical speech and
      language development (mean age = 5.9 years) was recorded and presented to 20
      listeners. Results were compared between the two groups and correlation with
      percentage of consonants correct (PCC) was examined. OUTCOMES & RESULTS: The
      intelligibility scores obtained correlated with PCC in single words and differed
      significantly between the two groups, indicating high validity. Inter-judge
      reliability, analysed using intra-class correlation (ICC), was excellent in terms
      of the average measure for several listeners. CONCLUSIONS & IMPLICATIONS: The
      results suggest that this method can be recommended for assessing
      intelligibility, especially if the mean across several listeners is used. It
      could also be used in clinical settings when evaluating intelligibility over
      time, provided that the same listener makes the assessments.

PMID- 24304872
TI  - Body mass evolution and diversification within horses (family Equidae).
AB  - Horses (family Equidae) are a classic example of adaptive radiation, exhibiting a
      nearly 60-fold increase in maximum body mass and a peak taxonomic diversity of
      nearly 100 species across four continents. Such patterns are commonly attributed
      to niche competition, in which increased taxonomic diversity drives increased
      size disparity. However, neutral processes, such as macroevolutionary
      'diffusion', can produce similar increases in disparity without increased
      diversity. Using a comprehensive database of Equidae species size estimates and a
      common mathematical framework, we measure the contributions of diversity-driven
      and diffusion-driven mechanisms for increased disparity during the Equidae
      radiation. We find that more than 90% of changes in size disparity are
      attributable to diffusion alone. These results clarify the role of species
      competition in body size evolution, indicate that morphological disparity and
      species diversity may be only weakly coupled in general, and demonstrate that
      large species may evolve from neutral macroevolutionary diffusion processes
      alone. 

PMID- 24304874
TI  - Oncogenes: direct hit on mutant RAS.

PMID- 24304873
TI  - Survivors of childhood and adolescent cancer: life-long risks and
      responsibilities.
AB  - Survival rates for most paediatric cancers have improved at a remarkable pace
      over the past four decades. In developed countries, cure is now the probable
      outcome for most children and adolescents who are diagnosed with cancer: their 5
      year survival rate approaches 80%. However, the vast majority of these cancer
      survivors will have at least one chronic health condition by 40 years of age. The
      burden of responsibility to understand the long-term morbidity and mortality that
      is associated with currently successful treatments must be borne by many,
      including the research and health care communities, survivor advocacy groups, and
      governmental and policy-making entities.

PMID- 24304875
TI  - Signalling: a new target for p53-null tumours.

PMID- 24304877
TI  - Orthodoxy and innovation: next practices for nursing education.

PMID- 24304876
TI  - Production and purification of polymerization-competent HIV-1 capsid protein p24
      (CA) in NiCo21(DE3) Escherichia coli.
AB  - BACKGROUND: HIV genome is packaged and organized in a conical capsid, which is
      made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary
      structural component and due to its critical roles in both late and early stages
      of the HIV replication cycle, CA has attracted increased interest as a drug
      discovery target in recent years. Drug discovery studies require large amounts of
      highly pure and biologically active protein. It is therefore desirable to
      establish a simple and reproducible process for efficient production of HIV-1 CA.
      RESULT: In this work, 6-His-tagged wild type CA from HIV-1 (NL4.3) was expressed
      in rare tRNA-supplemented NiCo21(DE3) Escherichia coli, and its production was
      studied in shake flask culture condition of expression. Influences of various key
      cultivation parameters were examined to identify optimal conditions for HIV-1 CA
      production. It was found that a culture temperature of 22 degrees C and induction
      with 0.05 mM IPTG at the early stage of growth were ideal, leading to a maximum
      biomass yield when grown in Super broth supplemented with 1% glucose. With
      optimized culture conditions, a final biomass concentration of ~27.7 g L-1 (based
      on optical density) was obtained in 12 hours post-induction, leading to a yield
      of about ~170 mg L-1 HIV-1 CA. A two-step purification strategy (chitin beads +
      IMAC) was employed, which efficiently removed metal affinity resin-binding
      bacterial proteins that contaminate recombinant His-tagged protein preparation,
      and resulted in highly pure HIV-1 CA. The purified protein was capable of
      polymerization when tested in an in vitro polymerization assay. CONCLUSIONS: By
      using this optimized expression and purification procedure, milligram amounts of
      highly pure and polymerization-competent recombinant HIV-1 CA can be produced at
      the lab-scale and thus used for further biochemical studies.

PMID- 24304878
TI  - Re: Integrated learning through student goal development.

PMID- 24304879
TI  - The three-question health literacy experience for baccalaureate nursing students.

PMID- 24304880
TI  - Facilitating a structured controversy using VoiceThread.

PMID- 24304881
TI  - Milder clinical aspects of X-linked Alport syndrome in men positive for the
      collagen IV alpha5 chain.
AB  - X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the
      type IV collagen alpha5 chain (alpha5(IV)). Complete absence of alpha5(IV) in the
      renal basal membrane is considered a pathological characteristic in male
      patients; however, positive alpha5(IV) staining has been found in over 20% of
      patients. We retrospectively studied 52 genetically diagnosed male X-linked
      Alport syndrome patients to evaluate differences in clinical characteristics and
      renal outcomes between 15 alpha5(IV)-positive and 37 alpha5(IV)-negative
      patients. Thirteen patients in the alpha5(IV)-positive group had non-truncating
      mutations consisting of nine missense mutations, three in-frame deletions, and
      one splice-site mutation resulting in small in-frame deletions of transcripts.
      The remaining two showed somatic mutations with mosaicism. Missense mutations in
      the alpha5(IV)-positive group were more likely to be located before exon 25
      compared with missense mutations in the alpha5(IV)-negative group. Furthermore,
      urinary protein levels were significantly lower and the age at onset of end-stage
      renal disease was significantly higher in the positive group than in the negative
      group. These results help to clarify the milder clinical manifestations and
      molecular characteristics of male X-linked Alport syndrome patients expressing
      the alpha5(IV) chain. 

PMID- 24304882
TI  - Klotho has dual protective effects on cisplatin-induced acute kidney injury.
AB  - Klotho protects the kidney from ischemia-reperfusion injury, but its effect on
      nephrotoxins is unknown. Here we determined whether Klotho protects the kidney
      from cisplatin toxicity. Cisplatin increased plasma creatinine and induced
      tubular injury, which were exaggerated in Klotho haplosufficient (Kl/+) and
      ameliorated in transgenic Klotho overexpressing (Tg-Kl) mice. Neutrophil
      gelatinase-associated lipocalin and active caspase-3 protein and the number of
      apoptotic cells in the kidney were higher in Kl/+ and lower in Tg-Kl compared
      with wild-type mice. Klotho suppressed basolateral uptake of cisplatin by the
      normal rat kidney cell line (NRK), an effect similar to cimetidine, a known
      inhibitor of organic cation transport (OCT). A decrease in cell surface and total
      OCT2 protein and OCT activity by Klotho was mimicked by beta-glucuronidase. The
      Klotho effect was attenuated by beta-glucuronidase inhibition. On the other hand,
      OCT2 mRNA was reduced by Klotho but not by beta-glucuronidase. Moreover,
      cimetidine inhibited OCT activity but not OCT2 expression. Unlike cimetidine,
      Klotho reduced cisplatin-induced apoptosis from either the basolateral or apical
      side and even when added after NRK cells were already loaded with cisplatin.
      Thus, Klotho protects the kidney against cisplatin nephrotoxicity by reduction of
      basolateral uptake of cisplatin by OCT2 and a direct anti-apoptotic effect
      independent of cisplatin uptake. Klotho may be a useful agent to prevent and
      treat cisplatin-induced nephrotoxicity. 

PMID- 24304883
TI  - Regulation of lipid accumulation by AMP-activated kinase [corrected] in high fat
      diet-induced kidney injury.
AB  - AMP-activated protein kinase (AMPK) is an important energy sensor that may be
      critical in regulating renal lipid accumulation. To evaluate the role of AMPK in
      mediating renal lipid accumulation, C57BL/6J mice were randomized to a standard
      diet, a high-fat diet, or a high-fat diet plus AICAR (an AMPK activator) for 14
      weeks. Renal functional and structural studies along with electron microscopy
      were performed. Mice given the high-fat diet had proximal tubule injury with the
      presence of enlarged clear vacuoles, and multilaminar inclusions concurrent with
      an increase of tissue lipid and overloading of the lysosomal system. The margins
      of the clear vacuoles were positive for the endolysosomal marker, LAMP1,
      suggesting lysosome accumulation. Characterization of vesicles by special stains
      (Oil Red O, Nile Red, Luxol Fast Blue) and by electron microscopy showed they
      contained onion skin-like accumulations consistent with phospholipids. Moreover,
      cholesteryl esters and phosphatidylcholine-containing phospholipids were
      significantly increased in the kidneys of mice on a high-fat diet. AMPK
      activation with chronic AICAR treatment prevented the clinical and structural
      effects of high-fat diet. Thus, high-fat diet contributes to a dysfunction of the
      lysosomal system and altered lipid metabolism characterized by cholesterol and
      phospholipid accumulation in the kidney. AMPK activation normalizes the changes
      in renal lipid content despite chronic exposure to lipid challenge. 

PMID- 24304884
TI  - Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis
      following acute kidney injury.
AB  - Fetal microchimeric cells (FMCs) enter the maternal circulation and persist in
      tissue for decades. They have capacity to home to injured maternal tissue and
      differentiate along that tissue's lineage. This raises the question of the
      origin(s) of cells transferred to the mother during pregnancy. FMCs with a
      mesenchymal phenotype have been documented in several studies, which makes
      mesenchymal stem cells an attractive explanation for their broad plasticity. Here
      we assessed the recruitment and mesenchymal lineage contribution of FMCs in
      response to acute kidney fibrosis induced by aristolochic acid injection. Serial
      in vivo bioluminescence imaging revealed a biphasic recruitment of active
      collagen-producing FMCs during the repair process of injured kidney in post
      partum wild-type mothers that had delivered transgenic pups expressing luciferase
      under the collagen type I-promoter. The presence of FMCs long-term post injury
      (day 60) was associated with profibrotic molecules (TGF-beta/CTGF), serum urea
      levels, and collagen deposition. Immunostaining confirmed FMCs at short term (day
      15) using post-partum wild-type mothers that had delivered green fluorescent
      protein-positive pups and suggested a mainly hematopoietic phenotype. We conclude
      that there is biphasic recruitment to, and activity of, FMCs at the injury site.
      Moreover, we identified five types of FMC, implicating them all in the reparative
      process at different stages of induced renal interstitial fibrosis. 

PMID- 24304885
TI  - Subclinical cardiovascular disease is associated with a high glomerular
      filtration rate in the nondiabetic general population.
AB  - A reduced glomerular filtration rate (GFR) in chronic kidney disease is a risk
      factor for cardiovascular disease. However, evidence indicates that a high GFR
      may also be a cardiovascular risk factor. This issue remains unresolved due to a
      lack of longitudinal studies of manifest cardiovascular disease with precise GFR
      measurements. Here, we performed a cross-sectional study of the relationship
      between high GFR measured as iohexol clearance and subclinical cardiovascular
      disease in the Renal Iohexol Clearance Survey in Tromso 6 (RENIS-T6), a
      representative sample of the middle-aged general population. A total of 1521
      persons without cardiovascular disease, chronic kidney disease, diabetes, or
      micro- or macroalbuminuria were examined with carotid ultrasonography and
      electrocardiography. The GFR in the highest quartile was associated with an
      increased odds ratio of having total carotid plaque area greater than the median
      of non-zero values (odds ratio 1.56, 95% confidence interval 1.02-2.39) or
      electrocardiographic signs of left ventricular hypertrophy (odds ratio 1.62, 95%
      confidence interval 1.10-2.38) compared to the lowest quartile. The analyses were
      adjusted for cardiovascular risk factors, urinary albumin excretion, and fasting
      serum glucose. Thus, high GFR is associated with carotid atherosclerosis and left
      ventricular hypertrophy and should be investigated as a possible risk factor for
      manifest cardiovascular disease in longitudinal studies. 

PMID- 24304886
TI  - Clinical significance of palliative gastrectomy on the survival of patients with
      incurable advanced gastric cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Palliative gastrectomy for patients with advanced gastric cancer
      remains controversial. The objective of the present meta-analysis was to analyze
      survival outcomes and establish a consensus on whether palliative gastrectomy is
      suitable for patients with incurable advanced gastric cancer and which type of
      patients should be selected to receive palliative gastrectomy. METHODS: A
      literature search was conducted in PubMed, EMBASE and the Cochrane Library. The
      results for overall survival in the meta-analysis are expressed as hazard ratios
      (HRs) with 95% confidence intervals (CIs). RESULTS: Of 1647 articles and
      abstracts reviewed, 14 studies with 3003 patients were eligible for the final
      analysis. The meta-analysis revealed that palliative gastrectomy is associated
      with a significantly improvement in overall survival (HR 0.56; 95%CI 0.39-0.80; p
      < 0.002) compared that of patients treated without palliative gastrectomy. An
      improvement in survival was also observed in patients with stage M1 gastric
      cancer who received palliative gastrectomy (HR 0.62; 95%CI 0.49-0.78; p <
      0.0001), especially those with peritoneal dissemination (HR = 0.76, 95%CI 0.63
      0.92), liver metastasis (HR = 0.41, 95%CI 0.30-0.55), or distant lymph-node
      metastasis (HR = 0.36, 95%CI 0.23-0.59). Combined hepatic resection may be
      beneficial for patients who under palliative gastrectomy (HR 0.30; 95%CI 0.15
      0.61; p = 0.0008). The overall survival of patients who underwent palliative
      gastrectomy combined with chemotherapy was significantly improved (HR 0.63; 95%CI
      0.47-0.84; p = 0.002). CONCLUSIONS: From the results of the meta-analysis,
      palliative gastrectomy for patients with incurable advanced gastric cancer may be
      associated with longer survival, especially for patients with stage M1 gastric
      cancer. Combined hepatic resection for patients with liver metastasis and
      chemotherapy may be beneficial factors compared to simple palliative gastrectomy.

PMID- 24304887
TI  - Influence of lateral cephalometric radiographs on extraction decision in skeletal
      class I patients.
AB  - BACKGROUND: Radiographic examination is considered 'justified' only when
      detection of a condition that would change the mechanisms and timing of treatment
      is possible. Radiographic safety guidelines have restricted the indication of
      lateral cephalometric radiographs (LCRs) to presence of distinct skeletal Class
      II or Class III. However, they are taken routinely in clinical practice and
      considered to be part of the 'gold' standard for orthodontic diagnosis.
      Therefore, the aim of this study was to test the null hypothesis that lateral
      cephalometric radiograph (LCR) evaluation would not alter the extraction/non
      extraction decision in orthodontic treatment planning of skeletal Class I
      patients. MATERIALS AND METHODS: Intraoral and extraoral photographs, dental
      casts and extraoral radiographs of 60 skeletal Class I patients were prepared
      digitally for assessment using a presentation software. One experienced (EO) and
      inexperienced orthodontist (IO) was asked to decide on extraction or non
      extraction on a Likert-type linear scale for treatment planning. This procedure
      was repeated 4 weeks later with a mixed order of patients and the LCRs being
      omitted. Kappa, Weighted Kappa (WK) and McNemar scores were computed to test
      decision consistency and Bland-Altman plots together with 95% limits of agreement
      were used to determine measurement accuracy and presence of systematic bias.
      RESULTS: Both EO (WK = 0.67) and IO (WK = 0.64) had good level of decision
      agreement with and without LCR evaluation. EO did not present a shift towards
      extraction nor non-extraction with LCR evaluation (McNemar = 0.999) whereas IO
      showed a tendency to extraction (McNemar = 0.07) with LCR data. Including LCR
      evaluation created a systematic inconsistency between EO and IO (Line of equality
      = 0.8, Confidence interval = 0.307-0.707). CONCLUSIONS: Lateral cephalometric
      radiograph evaluation did not influence the extraction decision in treatment
      planning of skeletal Class I patients. Reconsidering the necessity of lateral
      cephalograms in orthodontic treatment of skeletal Class I patients may reduce the
      amount of ionizing radiation. Key words: Lateral cephalometric radiograph,
      extraction, treatment planning, skeletal Class I.

PMID- 24304888
TI  - Organizational performance impacting patient satisfaction in Ontario hospitals: a
      multilevel analysis.
AB  - BACKGROUND: Patient satisfaction in health care constitutes an important
      component of organizational performance in the hospital setting. Satisfaction
      measures have been developed and used to evaluate and improve hospital
      performance, quality of care and physician practice. In order to direct
      improvement strategies, it is necessary to evaluate both individual and
      organizational factors that can impact patients' perception of care. The study
      aims were to determine the dimensions of patient satisfaction, and to analyze the
      individual and organizational determinants of satisfaction dimensions in
      hospitals. METHODS: We used patient and hospital survey data as well as
      administrative data collected for a 2008 public hospital report in Ontario,
      Canada. We evaluated the clustering of patient survey items with exploratory
      factor analysis and derived plausible dimensions of satisfaction. A two-level
      multivariate model was fitted to analyze the determinants of satisfaction.
      RESULTS: We found eight satisfaction factors, with acceptable to good level of
      loadings and good reliability. More than 95% of variation in patient satisfaction
      scores was attributable to patient-level variation, with less than 5%
      attributable to hospital-level variation. The hierarchical models explain 5 to
      17% of variation at the patient level and up to 52% of variation between
      hospitals. Individual patient characteristics had the strongest association with
      all dimensions of satisfaction. Few organizational performance indicators are
      associated with patient satisfaction and significant determinants differ
      according to the satisfaction dimension. CONCLUSIONS: The research findings
      highlight the importance of adjusting for both patient-level and organization
      level characteristics when evaluating patient satisfaction. Better understanding
      and measurement of organization-level activities and processes associated with
      patient satisfaction could contribute to improved satisfaction ratings and care
      quality.

PMID- 24304889
TI  - Expression Atlas update--a database of gene and transcript expression from
      microarray- and sequencing-based functional genomics experiments.
AB  - Expression Atlas (http://www.ebi.ac.uk/gxa) is a value-added database providing
      information about gene, protein and splice variant expression in different cell
      types, organism parts, developmental stages, diseases and other biological and
      experimental conditions. The database consists of selected high-quality
      microarray and RNA-sequencing experiments from ArrayExpress that have been
      manually curated, annotated with Experimental Factor Ontology terms and processed
      using standardized microarray and RNA-sequencing analysis methods. The new
      version of Expression Atlas introduces the concept of 'baseline' expression, i.e.
      gene and splice variant abundance levels in healthy or untreated conditions, such
      as tissues or cell types. Differential gene expression data benefit from an in
      depth curation of experimental intent, resulting in biologically meaningful
      'contrasts', i.e. instances of differential pairwise comparisons between two sets
      of biological replicates. Other novel aspects of Expression Atlas are its strict
      quality control of raw experimental data, up-to-date RNA-sequencing analysis
      methods, expression data at the level of gene sets, as well as genes and a more
      powerful search interface designed to maximize the biological value provided to
      the user. 

PMID- 24304890
TI  - Vespucci: a system for building annotated databases of nascent transcripts.
AB  - Global run-on sequencing (GRO-seq) is a recent addition to the series of high
      throughput sequencing methods that enables new insights into transcriptional
      dynamics within a cell. However, GRO-sequencing presents new algorithmic
      challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not
      address the unique problem of identifying transcriptional units de novo from
      short reads located all across the genome. Here, we present a novel algorithm for
      de novo transcript identification from GRO-sequencing data, along with a system
      that determines transcript regions, stores them in a relational database and
      associates them with known reference annotations. We use this method to analyze
      GRO-sequencing data from primary mouse macrophages and derive novel quantitative
      insights into the extent and characteristics of non-coding transcription in
      mammalian cells. In doing so, we demonstrate that Vespucci expands existing
      annotations for mRNAs and lincRNAs by defining the primary transcript beyond the
      polyadenylation site. In addition, Vespucci generates assemblies for un-annotated
      non-coding RNAs such as those transcribed from enhancer-like elements. Vespucci
      thereby provides a robust system for defining, storing and analyzing diverse
      classes of primary RNA transcripts that are of increasing biological interest. 

PMID- 24304891
TI  - Virus Variation Resource--recent updates and future directions.
AB  - Virus Variation (http://www.ncbi.nlm.nih.gov/genomes/VirusVariation/) is a
      comprehensive, web-based resource designed to support the retrieval and display
      of large virus sequence datasets. The resource includes a value added database, a
      specialized search interface and a suite of sequence data displays. Virus
      specific sequence annotation and database loading pipelines produce consistent
      protein and gene annotation and capture sequence descriptors from sequence
      records then map these metadata to a controlled vocabulary. The database supports
      a metadata driven, web-based search interface where sequences can be selected
      using a variety of biological and clinical criteria. Retrieved sequences can then
      be downloaded in a variety of formats or analyzed using a suite of tools and
      displays. Over the past 2 years, the pre-existing influenza and Dengue virus
      resources have been combined into a single construct and West Nile virus added to
      the resultant resource. A number of improvements were incorporated into the
      sequence annotation and database loading pipelines, and the virus-specific search
      interfaces were updated to support more advanced functions. Several new features
      have also been added to the sequence download options, and a new multiple
      sequence alignment viewer has been incorporated into the resource tool set.
      Together these enhancements should support enhanced usability and the inclusion
      of new viruses in the future. 

PMID- 24304892
TI  - miRTarBase update 2014: an information resource for experimentally validated
      miRNA-target interactions.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively
      regulating gene expression to control many cellular mechanisms. The miRTarBase
      database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and
      comprehensive information of experimentally validated miRNA-target interactions.
      The database was launched in 2010 with data sources for >100 published studies in
      the identification of miRNA targets, molecular networks of miRNA targets and
      systems biology, and the current release (2013, version 4) includes significant
      expansions and enhancements over the initial release (2010, version 1). This
      article reports the current status of and recent improvements to the database,
      including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a
      miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv)
      miRNA target-associated diseases and (v) additional utilities including an
      upgrade reminder and an error reporting/user feedback system. 

PMID- 24304893
TI  - DICE, an efficient system for iterative genomic editing in human pluripotent stem
      cells.
AB  - To reveal the full potential of human pluripotent stem cells, new methods for
      rapid, site-specific genomic engineering are needed. Here, we describe a system
      for precise genetic modification of human embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located
      in a safe, intergenic, transcriptionally active region of chromosome 22, as the
      recipient site, to provide robust, ubiquitous expression of inserted genes.
      Recipient cell lines were established by site-specific placement of a 'landing
      pad' cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus
      by spontaneous or TALEN-assisted homologous recombination. Dual integrase
      cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to
      insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus,
      replacing the landing pad. This system provided complete control over content,
      direction and copy number of inserted genes, with a specificity of 100%. A series
      of genes, including mCherry and various combinations of the neural transcription
      factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from
      H9 ESC, as well as iPSC lines derived from a Parkinson's disease patient and a
      normal sibling control. The DICE system offers rapid, efficient and precise gene
      insertion in ESC and iPSC and is particularly well suited for repeated
      modifications of the same locus. 

PMID- 24304894
TI  - canSAR: updated cancer research and drug discovery knowledgebase.
AB  - canSAR (http://cansar.icr.ac.uk) is a public integrative cancer-focused
      knowledgebase for the support of cancer translational research and drug
      discovery. Through the integration of biological, pharmacological, chemical,
      structural biology and protein network data, it provides a single information
      portal to answer complex multidisciplinary questions including--among many others
      -what is known about a protein, in which cancers is it expressed or mutated, and
      what chemical tools and cell line models can be used to experimentally probe its
      activity? What is known about a drug, its cellular sensitivity profile and what
      proteins is it known to bind that may explain unusual bioactivity? Here we
      describe major enhancements to canSAR including new data, improved search and
      browsing capabilities and new target, cancer cell line, protein family and 3D
      structure summaries and tools.

PMID- 24304895
TI  - BacMet: antibacterial biocide and metal resistance genes database.
AB  - Antibiotic resistance has become a major human health concern due to widespread
      use, misuse and overuse of antibiotics. In addition to antibiotics, antibacterial
      biocides and metals can contribute to the development and maintenance of
      antibiotic resistance in bacterial communities through co-selection. Information
      on metal and biocide resistance genes, including their sequences and molecular
      functions, is, however, scattered. Here, we introduce BacMet
      (http://bacmet.biomedicine.gu.se)--a manually curated database of antibacterial
      biocide- and metal-resistance genes based on an in-depth review of the scientific
      literature. The BacMet database contains 470 experimentally verified resistance
      genes. In addition, the database also contains 25 477 potential resistance genes
      collected from public sequence repositories. All resistance genes in the BacMet
      database have been organized according to their molecular function and induced
      resistance phenotype.

PMID- 24304896
TI  - CellFinder: a cell data repository.
AB  - CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for
      molecular data characterizing mammalian cells in different tissues and in
      different development stages. It is built from carefully selected data sets
      stemming from other curated databases and the biomedical literature. To date,
      CellFinder describes 3394 cell types and 50 951 cell lines. The database
      currently contains 3055 microscopic and anatomical images, 205 whole-genome
      expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553
      905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000
      publications followed by manual curation confirmed expression information on ~900
      proteins and genes. CellFinder's data model is capable to seamlessly represent
      entities from single cells to the organ level, to incorporate mappings between
      homologous entities in different species and to describe processes of cell
      development and differentiation. Its ontological backbone currently consists of
      204 741 ontology terms incorporated from 10 different ontologies unified under
      the novel CELDA ontology. CellFinder's web portal allows searching, browsing and
      comparing the stored data, interactive construction of developmental trees and
      navigating the partonomic hierarchy of cells and tissues through a unique body
      browser designed for life scientists and clinicians. 

PMID- 24304897
TI  - Plasma Proteome Database as a resource for proteomics research: 2014 update.
AB  - Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was
      initially described in the year 2005 as a part of Human Proteome Organization's
      (HUPO's) pilot initiative on Human Plasma Proteome Project. Since then,
      improvements in proteomic technologies and increased throughput have led to
      identification of a large number of novel plasma proteins. To keep up with this
      increase in data, we have significantly enriched the proteomic information in
      PPD. This database currently contains information on 10,546 proteins detected in
      serum/plasma of which 3784 have been reported in two or more studies. The latest
      version of the database also incorporates mass spectrometry-derived data
      including experimentally verified proteotypic peptides used for multiple reaction
      monitoring assays. Other novel features include published plasma/serum
      concentrations for 1278 proteins along with a separate category of plasma-derived
      extracellular vesicle proteins. As plasma proteins have become a major thrust in
      the field of biomarkers, we have enabled a batch-based query designated Plasma
      Proteome Explorer, which will permit the users in screening a list of proteins or
      peptides against known plasma proteins to assess novelty of their data set. We
      believe that PPD will facilitate both clinical and basic research by serving as a
      comprehensive reference of plasma proteins in humans and accelerate biomarker
      discovery and translation efforts.

PMID- 24304898
TI  - Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through
      organization of DNA bases in the presynaptic filament.
AB  - The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand
      exchange reaction, a crucial step in homologous recombination. To clarify how
      this accessory protein acts on the strand exchange reaction, we have analyzed how
      the structure of the primary reaction intermediate, the Rad51/single-stranded DNA
      (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1.
      Using flow linear dichroism spectroscopy, we observe that the nucleobases of the
      ssDNA are more perpendicularly aligned to the filament axis in the presence of
      Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5
      Sfr1. When using a modified version of the natural protein where the N-terminal
      part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to
      stimulate the strand exchange reaction, we still observe the improved
      perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its
      activating effect through interaction with the Rad51 filament mainly and not with
      the DNA. We propose that the role of a coplanar alignment of nucleobases induced
      by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical
      matching with an invading double-stranded DNA, hence stimulating the strand
      exchange reaction. 

PMID- 24304899
TI  - SCOPe: Structural Classification of Proteins--extended, integrating SCOP and
      ASTRAL data and classification of new structures.
AB  - Structural Classification of Proteins-extended (SCOPe, http://scop.berkeley.edu)
      is a database of protein structural relationships that extends the SCOP database.
      SCOP is a manually curated ordering of domains from the majority of proteins of
      known structure in a hierarchy according to structural and evolutionary
      relationships. Development of the SCOP 1.x series concluded with SCOP 1.75. The
      ASTRAL compendium provides several databases and tools to aid in the analysis of
      the protein structures classified in SCOP, particularly through the use of their
      sequences. SCOPe extends version 1.75 of the SCOP database, using automated
      curation methods to classify many structures released since SCOP 1.75. We have
      rigorously benchmarked our automated methods to ensure that they are as accurate
      as manual curation, though there are many proteins to which our methods cannot be
      applied. SCOPe is also partially manually curated to correct some errors in SCOP.
      SCOPe aims to be backward compatible with SCOP, providing the same parseable
      files and a history of changes between all stable SCOP and SCOPe releases. SCOPe
      also incorporates and updates the ASTRAL database. The latest release of SCOPe,
      2.03, contains 59 514 Protein Data Bank (PDB) entries, increasing the number of
      structures classified in SCOP by 55% and including more than 65% of the protein
      structures in the PDB. 

PMID- 24304901
TI  - GPCRDB: an information system for G protein-coupled receptors.
AB  - For the past 20 years, the GPCRDB (G protein-coupled receptors database;
      http://www.gpcr.org/7tm/) has been a 'one-stop shop' for G protein-coupled
      receptor (GPCR)-related data. The GPCRDB contains experimental data on sequences,
      ligand-binding constants, mutations and oligomers, as well as many different
      types of computationally derived data, such as multiple sequence alignments and
      homology models. The GPCRDB also provides visualization and analysis tools, plus
      a number of query systems. In the latest GPCRDB release, all multiple sequence
      alignments, and >65,000 homology models, have been significantly improved, thanks
      to a recent flurry of GPCR X-ray structure data. Tools were introduced to browse
      X-ray structures, compare binding sites, profile similar receptors and generate
      amino acid conservation statistics. Snake plots and helix box diagrams can now be
      custom coloured (e.g. by chemical properties or mutation data) and saved as
      figures. A series of sequence alignment visualization tools has been added, and
      sequence alignments can now be created for subsets of sequences and sequence
      positions, and alignment statistics can be produced for any of these subsets.

PMID- 24304900
TI  - The dual role of HOP2 in mammalian meiotic homologous recombination.
AB  - Deletion of Hop2 in mice eliminates homologous chromosome synapsis and disrupts
      double-strand break (DSB) repair through homologous recombination. HOP2 in vitro
      shows two distinctive activities: when it is incorporated into a HOP2-MND1
      complex it stimulates DMC1 and RAD51 recombination activities and the purified
      HOP2 alone is proficient in promoting strand invasion. We observed that a
      fraction of Mnd1(-/-) spermatocytes, which express HOP2 but apparently have
      inactive DMC1 and RAD51 due to lack of the HOP2-MND1 complex, exhibits a high
      level of chromosome synapsis and that most DSBs in these spermatocytes are
      repaired. This suggests that DSB repair catalyzed solely by HOP2 supports
      homologous chromosome pairing and synapsis. In addition, we show that in vitro
      HOP2 promotes the co-aggregation of ssDNA with duplex DNA, binds to ssDNA leading
      to unstacking of the bases, and promotes the formation of a three-strand synaptic
      intermediate. However, HOP2 shows distinctive mechanistic signatures as a
      recombinase. Namely, HOP2-mediated strand exchange does not require ATP and, in
      contrast to DMC1, joint molecules formed by HOP2 are more sensitive to mismatches
      and are efficiently dissociated by RAD54. We propose that HOP2 may act as a
      recombinase with specific functions in meiosis. 

PMID- 24304902
TI  - Assisted reproductive technology surveillance -- United States, 2010.
AB  - PROBLEM/CONDITION: Since the first U.S. infant conceived with Assisted
      Reproductive Technology (ART) was born in 1981, both the use of advanced
      technologies to overcome infertility and the number of fertility clinics
      providing ART services have increased steadily in the United States. ART includes
      fertility treatments in which both eggs and sperm are handled in the laboratory
      (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo
      ART procedures are more likely to deliver multiple-birth infants than those who
      conceive naturally because more than one embryo might be transferred during a
      procedure. Multiple births pose substantial risks to both mothers and infants,
      including pregnancy complications, preterm delivery, and low birthweight infants.
      This report provides state-specific information on U.S. ART procedures performed
      in 2010 and compares infant outcomes that occurred in 2010 (resulting from
      procedures performed in 2009 and 2010) with outcomes for all infants born in the
      United States in 2010. REPORTING PERIOD COVERED: 2010. DESCRIPTION OF SYSTEM: In
      1996, CDC began collecting data on all ART procedures performed in fertility
      clinics in the United States and U.S. territories, as mandated by the Fertility
      Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493).
      Data are collected through the National ART Surveillance System (NASS), a web
      based data collecting system developed by CDC. RESULTS: In 2010, a total of
      147,260 ART procedures performed in 443 U.S. fertility clinics were reported to
      CDC. These procedures resulted in 47,090 live-birth deliveries and 61,564
      infants. The largest numbers of ART procedures were performed among residents of
      six states: California (18,524), New York (excluding New York City) (14,212),
      Illinois (10,110), Massachusetts (9,854), New Jersey (8,783), and Texas (8,754).
      These six states also had the highest number of live-birth deliveries as a result
      of ART procedures and together accounted for 48.0% of all ART procedures
      performed, 45.0% of all infants born from ART, and 45.0% of all multiple live
      birth deliveries but only 34.0% of all infants born in the United States and U.S.
      territories. Nationally, the average number of ART procedures performed per 1
      million women of reproductive age (15-44 years), which is a proxy indicator of
      ART use, was 2,331. In 13 states (California, Connecticut, Delaware, Hawaii,
      Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York,
      Pennsylvania, Rhode Island, and Virginia), this proxy measure was higher than the
      national rate, and in four states (Connecticut, Massachusetts, New Jersey, and
      New York) and the District of Columbia, it exceeded twice the national rate.
      Nationally, among cycles in which at least one embryo was transferred, the
      average number of embryos transferred increased with increasing age (2.0 among
      women aged <35 years, 2.4 among women aged 35-40 years, and 3.0 among women aged
      >40 years). Elective single-embryo transfer (eSET) rates decreased with
      increasing age (10.0% among women aged <35 years, 3.8% among women aged 35-40
      years, and 0.6% among women aged >40 years). ESET rates also varied substantially
      between states (range: 0 to 45.0% among women aged <35 years). The number of ART
      births as a percentage of total infants born in the state or territory is
      considered as another measure of ART use. Overall, ART contributed to 1.5% of
      U.S. births (range: 0.1% in Guam to 4.8% in Massachusetts) with the highest rates
      (>3.5% of all infants born) observed in four states (Connecticut, Massachusetts,
      New Jersey, and New York), and the District of Columbia. The proportion of ART
      births was <=2.5% in the remaining states and territories. Infants conceived with
      ART comprised 20.0% of all multiple-birth infants (range: 0 in Guam to 40.5% in
      Massachusetts), 19.0% of all twin infants (range: 0 in Guam to 40.0% in
      Massachusetts), and 33.0% of triplet or higher order infants (range: 0 in several
      states to 60.0% in Arizona). Among infants conceived with ART, 46.0% were born in
      multiple deliveries (range: 0 in Guam to 55.4% in Utah), compared with only 3.0%
      of infants among all births in the general population (range: 1.3% in Guam to
      4.7% in Connecticut). A substantial proportion (43.4%) of ART-conceived infants
      were twin infants, and a smaller proportion (3.0%) were triplets and higher order
      infants. Nationally, infants conceived with ART comprised 5.6% of all low
      birthweight (<2,500 grams) infants (range: 0 in Guam to 16.0% in Massachusetts)
      and 5.6% of all very low birthweight (<1,500 grams) infants (range: 0 in Guam to
      15.8% in Massachusetts). Overall, among ART-conceived infants, 31.6% were low
      birthweight (range: 22.6% in New Hampshire to 48.2% in Puerto Rico), compared
      with 8.0% among all infants (range: 5.7% in Alaska to 12.6% in Puerto Rico); 5.6%
      of ART infants were very low birthweight (range: 1.9% in Maine to 14.3% in
      Montana), compared with 1.4% among all infants (range: 0.9% in Alaska to 2.3% in
      the District of Columbia). Finally, ART-conceived infants comprised 4.4% of all
      infants born preterm (<37 weeks; range: 0 in Guam to 13.3% in Massachusetts) and
      4.9% of all infants born very preterm (<32 weeks; range: 0 in Guam to 16.2% in
      Massachusetts). Overall, among infants conceived with ART, 36.6% were born
      preterm (range: 23.6% in New Hampshire to 56.8% in Wyoming), compared with 12.0%
      among all infants born in the general population (range: 8.4% in Vermont to 17.9%
      in Guam); 6.6% of ART infants were born very preterm (range: 0 in Maine to 14.5%
      in Puerto Rico), compared with 2.0% among all infants born in the general
      population (range: 1.3% in Alaska to 3.0% in the District of Columbia).
      INTERPRETATION: The percentage of infants conceived with ART varied considerably
      by state and territory (range: 0.1% to 4.8%). In most states, multiples from ART
      comprised a substantial proportion of all twin, triplet, and higher-order infants
      born in the state, and the rates of low birthweight and preterm infants were
      disproportionately higher among ART infants than in the birth population overall.
      Even among women aged <35 years, for whom single embryo transfers should be
      considered (particularly in patients with a favorable prognosis) according to
      American Society of Reproductive Medicine (ASRM) guidelines, on average, two
      embryos were transferred per cycle in ART procedures, influencing the overall
      multiple infant rates in the United States. ART use per population unit was
      distributed disproportionately in the United States, with only 13 states showing
      ART use above the national rate, which might suggest barriers to ART services in
      the remaining states. Of the four states (Illinois, Massachusetts, New Jersey,
      and Rhode Island) with comprehensive statewide-mandated health insurance coverage
      for ART procedures (e.g., coverage for at least four cycles of IVF), three states
      (Illinois, Massachusetts, and New Jersey) also had rates of ART use >1.5 times
      the national level. This type of mandated insurance has been associated with
      greater use of ART and might account for the differences observed in other
      states. PUBLIC HEALTH ACTIONS: Reducing the number of embryos transferred per ART
      procedure among all age groups and promotion of eSET procedures, when clinically
      appropriate, is needed to reduce multiple births, including twin births, and
      related adverse consequences of ART. Improved patient education and counseling on
      the risks of twins might be useful in reducing twin births because twins account
      for the majority of multiples. Although ART contributes to increasing rates of
      multiple births, it does not explain all of the increases, and therefore the
      possible role of non-ART fertility treatments warrants further study.

PMID- 24304903
TI  - Nurses' self-efficacy and practices relating to weight management of adult
      patients: a path analysis.
AB  - BACKGROUND: Health professionals play a key role in the prevention and treatment
      of excess weight and obesity, but many have expressed a lack of confidence in
      their ability to manage obese patients with their delivery of weight-management
      care remaining limited. The specific mechanism underlying inadequate practices in
      professional weight management remains unclear. The primary purpose of this study
      was to examine a self-efficacy theory-based model in understanding Registered
      Nurses' (RNs) professional performance relating to weight management. METHODS: A
      self-report questionnaire was developed based upon the hypothesized model and
      administered to a convenience sample of 588 RNs. Data were collected regarding
      socio-demographic variables, psychosocial variables (attitudes towards obese
      people, professional role identity, teamwork beliefs, perceived skills, perceived
      barriers and self-efficacy) and professional weight management practices.
      Structural equation modeling was conducted to identify correlations between the
      above variables and to test the goodness of fit of the proposed model. RESULTS:
      The survey response rate was 71.4% (n = 420). The respondents reported a moderate
      level of weight management practices. Self-efficacy directly and positively
      predicted the weight management practices of the RNs (beta = 0.36, p < 0.01), and
      fully or partially mediated the relationships between perceived skills, perceived
      barriers, professional role identity and teamwork beliefs and weight management
      practices. The final model constructed in this study demonstrated a good fit to
      the data [chi2 (14) =13.90, p = 0.46; GFI = 0.99; AGFI = 0.98; NNFI = 1.00; CFI =
      1.00; RMSEA = 0.00; AIC = 57.90], accounting for 38.4% and 43.2% of the variance
      in weight management practices and self-efficacy, respectively. CONCLUSIONS: Self
      efficacy theory appears to be useful in understanding the weight management
      practices of RNs. Interventions targeting the enhancement of self-efficacy may be
      effective in promoting RNs' professional performance in managing overweight and
      obese patients.

PMID- 24304904
TI  - The phosphate of pyridoxal-5'-phosphate is an acid/base catalyst in the mechanism
      of Pseudomonas fluorescens kynureninase.
AB  - Kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) catalyzes the hydrolytic
      cleavage of L-kynurenine to L-alanine and anthranilic acid. The proposed
      mechanism of the retro-Claisen reaction requires extensive acid/base catalysis.
      Previous crystal structures showed that Tyr226 in the Pseudomonas fluorescens
      enzyme (Tyr275 in the human enzyme) hydrogen bonds to the phosphate of the
      pyridoxal-5'-phosphate (PLP) cofactor. This Tyr residue is strictly conserved in
      all sequences of kynureninase. The human enzyme complexed with a competitive
      inhibitor, 3-hydroxyhippuric acid, showed that the ligand carbonyl O is located
      3.7 A from the phenol of Tyr275 (Lima, S., Kumar, S., Gawandi, V., Momany, C. &
      Phillips, R. S. (2009) J. Med. Chem. 52, 389-396). We prepared a Y226F mutant of
      P. fluorescens kynureninase to probe the role of this residue in catalysis. The
      Y226F mutant has approximately 3000-fold lower activity than wild-type, and does
      not show the pKa values of 6.8 on kcat and 6.5 and 8.8 on k(cat)/K(m) seen for
      the wild-type enzyme (Koushik, S. V., Moore, J. A. III, Sundararaju, B. &
      Phillips, R. S. (1998) Biochemistry 37, 1376-1382). Wild-type kynureninase shows
      a resonance at 4.5 ppm in (31)P-NMR, which is shifted to 5.0, 3.3 and 2.0 ppm
      when the potent inhibitor 5-bromodihydrokynurenine is added. However, Y226F
      kynureninase shows resonances at 3.6 and 2.5 ppm, and no change in the peak
      position is seen when 5-bromodihydrokynurenine is added. Taken together, these
      results suggest that Tyr226 mediates proton transfer between the substrate and
      the phosphate, which accelerates formation of external aldimine and gem-diol
      intermediates. Thus, the phosphate of PLP acts as an acid/base catalyst in the
      mechanism of kynureninase.

PMID- 24304905
TI  - Topographical guidance of 3D tumor cell migration at an interface of collagen
      densities.
AB  - During cancer progression, metastatic cells leave the primary tumor and invade
      into the fibrous extracellular matrix (ECM) within the surrounding stroma. This
      ECM network is highly heterogeneous, and interest in understanding how this
      network can affect cell behavior has increased in the past several decades.
      However, replicating this heterogeneity has proven challenging. Here, we designed
      and utilized a method to create a well-defined interface between two distinct
      regions of high- and low-density collagen gels to mimic the heterogeneities in
      density found in the tumor stroma. We show that cells will invade preferentially
      from the high-density side into the low-density side. We also demonstrate that
      the net cell migration is a function of the density of the collagen in which the
      cells are embedded, and the difference in density between the two regions has
      minimal effect on cell net displacement and distance travelled. Our data further
      indicate that a low-to-high density interface promotes directional migration and
      induces formation of focal adhesion on the interface surface. Together, the
      current results demonstrate how ECM heterogeneities, in the form of interfacial
      boundaries, can affect cell migration. 

PMID- 24304906
TI  - Myocardial injury in dogs with snake envenomation and its relation to systemic
      inflammation.
AB  - OBJECTIVE: To investigate the presence of myocardial injury in dogs hospitalized
      for snake envenomation and to examine its relationship with systemic
      inflammation. DESIGN: Prospective case-control study. SETTING: University
      teaching hospital and small animal referral hospital. ANIMALS: Dogs naturally
      envenomed by the European viper (Vipera berus; n = 24), African puff adder (Bitis
      arietans; n = 5), or snouted cobra (Naja annulifera; n = 9). INTERVENTIONS: Blood
      was collected from dogs envenomed by V. berus at admission, 12-24 hours
      postadmission, and 5-10 days postadmission. Blood was collected from dogs
      envenomed by B. arietans or N. annulifera at admission, and 12, 24, and 36 hours
      postadmission. MEASUREMENTS AND MAIN RESULTS: Concentrations of cardiac troponin
      I (cTnI), a marker of myocardial injury, and C-reactive protein (CRP), a marker
      of systemic inflammation, were measured in each blood sample. Evidence of
      myocardial injury was found in 58% of dogs envenomed by V. berus at one or more
      time points. A significant correlation between cTnI and CRP concentrations was
      found at all time points. Evidence of myocardial injury was found in 80% of dogs
      envenomed by B. arietans at one or more time points; however, no correlation was
      found between cTnI and CRP concentrations. Evidence of myocardial injury was
      found in 67% of dogs envenomed by N. annulifera at one or more time points. A
      significant correlation between cTnI and CRP concentrations was found at
      admission, but not at other time points. CONCLUSIONS: Myocardial injury
      frequently occurred in dogs with snake envenomation. While the degree of systemic
      inflammation was significantly correlated with degree of myocardial injury in V.
      berus envenomation at all time points, this was not the case in dogs envenomed by
      N. annulifera or B. arietans. This could be due to differences in the toxic
      substances of the snake venoms or to differences in the cytokines induced by the
      venom toxins.

PMID- 24304908
TI  - Ahmed valve, suture-less implantation: A new approach to an easier technique.
AB  - PURPOSE: Tissue adhesives have been used in ophthalmology instead of sutures to
      minimize the operating time. This case series investigated the effectiveness and
      safety of use of cyanoacrylate in Ahmed valve implantation through pars plana for
      refractory glaucoma. PATIENTS AND METHODS: Seventeen eyes of 17 patients with
      refractory glaucoma underwent Ahmed valve scleral suture-less implantation
      through pars plana with a cyanoacrylate suture of the plate. Refractory glaucoma
      was defined as intraocular pressure (IOP) >= 21 mm Hg with antiglaucoma eye
      drops, good adherence to treatment, and no previous glaucoma surgery. IOP control
      and development of complications were evaluated during the follow-up (mean follow
      up, 13.23 mo, 6 to 28 mo). RESULTS: IOP control, defined as IOP <= 21 mm Hg with
      or without antiglaucoma eye drops, was achieved in 82.2% of patients, and 58.8%
      were able to eliminate antiglaucoma eye drops. Mean surgical time was 9.76 +/-
      2.60 and 6 +/- 0.81 minutes in patients with previous vitrectomy (4 cases).
      Postoperative complications included transiently increased IOP, transient
      hyphema, early postoperative hypotony (4 cases), and tube block by the vitreous
      (2 cases): 1 resolved by Nd:YAG and the other by second vitrectomy. No cases of
      tube or plate extrusion, plate migration, choroidal or retinal detachment, or
      vitreous hemorrhage were observed. CONCLUSIONS: These results are promising and
      demonstrate a safe and effective alternative to the traditional scleral suture.
      Our data suggest that Ahmed valve implantation through pars plana with
      cyanoacrylate is a safe and effective method for refractory glaucoma. Further
      studies are needed to confirm our observation.

PMID- 24304907
TI  - The conundrum of causality in tumor virology: the cases of KSHV and MCV.
AB  - Controversy has plagued tumor virology since the first tumor viruses were
      described over 100 years ago. Methods to establish cancer causation, such as
      Koch's postulates, work poorly or not at all for these viruses. Kaposi's sarcoma
      herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using
      nucleic acid identification methods but they represent opposite poles in the
      patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk
      factors that contribute to infection and subsequent cancers. MCV and Merkel cell
      carcinoma (MCC), in contrast, is an example in which mutations to our normal
      viral flora contribute to cancer. Given the near-ubiquity of human MCV infection,
      establishing cancer causality relies on molecular evidence that does not fit
      comfortably within traditional infectious disease epidemiological models. These
      two viruses reveal some of the challenges and opportunities for inferring viral
      cancer causation in the age of molecular biology. 

PMID- 24304909
TI  - Clinician percent syllables stuttered, clinician severity ratings and speaker
      severity ratings: are they interchangeable?
AB  - BACKGROUND: At present, percent syllables stuttered (%SS) is the gold standard
      outcome measure for behavioural stuttering treatment research. However, ordinal
      severity rating (SR) procedures have some inherent advantages over that method.
      AIMS: To establish the relationship between Clinician %SS, Clinician SR and self
      reported Speaker SR. To investigate whether Clinician SRs and Speaker SRs can be
      used interchangeably. METHOD & PROCEDURES: Participants were three experienced
      speech-language pathologist (SLP) judges and 87 adults who stuttered. Adults who
      stuttered received a 10-min unscheduled telephone call at the conclusion of which
      they self-reported a SR using a nine-point scale. The SLPs measured the
      stuttering for these conversations with %SS and also with the SR scale. The mean
      scores for Clinician %SS and Clinician SR were compared with Speaker SR using
      appropriate indices of relative and absolute reliability. Relative reliability
      indices deal with the rank order of participants in a sample and whether they can
      be distinguished from each other. However, absolute reliability indices are
      related to the closeness of the measurement scores to each other and to a
      hypothetical true score. OUTCOMES & RESULTS: Strong correlations were found
      between Clinician %SS and Clinician SR, and also between Clinician %SS and
      Speaker SR, although with higher values in the former case. Additionally, very
      high correlations showed acceptable relative reliability between Clinician SR and
      Speaker SR. However, absolute reliability in terms of standard error of
      measurement and limits of agreement was poor for Clinician SR and Speaker SR.
      CONCLUSIONS & IMPLICATIONS: The results suggest that Clinician SR and Speaker SR
      cannot be used interchangeably to measure temporal stuttering severity changes
      for an individual client. However, researchers might use these two measures
      interchangeably in research contexts, such as clinical trials, where changes of
      the entire group are of interest to determine and compare treatment effect size
      across trials.

PMID- 24304910
TI  - Structural requirements for RNA degradation by HIV-1 reverse transcriptase.

PMID- 24304911
TI  - Reply to "Structural requirements for RNA degradation by HIV-1 reverse
      transcriptase".

PMID- 24304912
TI  - Poly-combing the genome for RNA.
AB  - An unresolved question in mammalian epigenetic regulation is how ubiquitously
      expressed chromatin-modifying complexes such as Polycomb group complex 2 (PRC2)
      find their specific target sites across an intricate choreography of localization
      events in time and space. Two recent studies now provide critical new insights
      into an intriguing genome-wide role for RNA in PRC2 regulation.

PMID- 24304913
TI  - A mediator methylation mystery: JMJD1C demethylates MDC1 to regulate DNA repair.
AB  - Mediator of DNA-damage checkpoint 1 (MDMDC1) has a central role in repair of DNA
      double-strand breaks (DSBs) by both homologous recombination and nonhomologous
      end joining, and its function is regulated by post-translational phosphorylation,
      ubiquitylation and sumoylation. In this issue, a new study by Watanabe et al.
      reveals that methylation of MDMDC1 is also critical for its function in DSB
      repair and specifically affects repair through BRCA1-dependent homologous
      recombination.

PMID- 24304914
TI  - PrimPol breaks replication barriers.
AB  - Faithful bypass of replication forks encountering obstructive DNA lesions is
      essential to prevent fork collapse and cell death. PrimPol is a new human primase
      and translesion polymerase that is able to bypass fork-blocking UV-induced
      lesions and to restart replication by origin-independent repriming.

PMID- 24304918
TI  - Effect of a DIVA vaccine with and without in-feed use of coated calcium-butyrate
      on transmission of Salmonella Typhimurium in pigs.
AB  - BACKGROUND: For satisfactory Salmonella control, good biosecurity along the pork
      production chain is crucial, although additional control measures on-farm need to
      be considered. This study evaluated the effect of two potential control measures
      against the spread of Salmonella Typhimurium via a transmission experiment with
      56 piglets (3-15 weeks of age): two groups were orally vaccinated with 107 - 108
      Colony Forming Units (CFU)/2 mL of a new attenuated Salmonella Typhimurium
      vaccine 'Salmoporc-?rfaJ' with DIVA capacities (Differentiation between Infected
      and Vaccinated Animals) (n = 2x16); the feed of one group was additionally
      supplemented with coated calcium-butyrate salt. Two weeks post vaccination, four
      pigs per group were orally challenged with 107 CFU/2 mL of a Salmonella
      Typhimurium strain 112910a. Both groups were compared with a positive
      (challenged/untreated; n = 16) and negative (unchallenged/untreated; n = 8)
      control group. Until six weeks post challenge, blood, individual faecal and
      finally tissue samples were examined. Adjusted transmission ratios 'Ra' were
      estimated, based on the challenge strain isolation from faecal and/or tissue
      samples. RESULTS: In both intervention groups, Ra values were lower compared to
      the positive control group, although these differences were not significant. In
      the combination group DIVA vaccine + coated butyrate, less non-challenged contact
      animals excreted Salmonella and less tissue samples were found Salmonella
      positive in all pigs, when compared to the positive control group (P < 0.01).
      Seroconversion was detected in none of the vaccinated animals before challenge,
      when using a commercial lipopolysaccharide (LPS) ELISA targeting only Salmonella
      O-antigens, deleted in this vaccine. This was in contrast with an in-house whole
      cell ELISA testing for various Salmonella antigens, in which Salmonella-specific
      antibodies were found pre-challenge in the serum of the vaccinated pigs.
      CONCLUSIONS: Both interventions showed a limited, non-significant reduction of
      Salmonella transmission between piglets. They may have applications towards
      Salmonella control and surveillance. Firstly, the number of Salmonella excreting
      contact pigs was significantly lower in the group where vaccination was combined
      with coated calcium-butyrate salt in the feed; secondly, the new vaccine
      confirmed its DIVA capacity. Therefore, these interventions merit further
      research with larger sample sizes, to optimize their use for Salmonella
      programmes.

PMID- 24304919
TI  - DNA aptamers that target human glioblastoma multiforme cells overexpressing
      epidermal growth factor receptor variant III in vitro.
AB  - AIM: Aptamers are oligonucleic acid or peptide molecules that bind to a specific
      target molecule in cells, thus may act as effective vehicles for drug or siRNA
      delivery. In this study we investigated the DNA aptamers that target human
      glioblastoma multiforme (GBM) cells overexpressing epidermal growth factor
      receptor variant III (EGFRvIII), which was linked to radiation and
      chemotherapeutic resistance of this most aggressive brain tumor. METHODS: A 73
      mer ssDNA library containing molecules with 30 nt of random sequence flanked by
      two primer hybridization sites was chosen as the initial library. Cell systematic
      evolution of ligands by exponential enrichment (Cell-SELEX) method was used to
      select the DNA aptamers that target EGFRvIII. The binding affinity of the
      aptamers was measured using a cell-based biotin-avidin ELISA. RESULTS: After 14
      rounds of selection, four DNA aptamers (32, 41, 43, and 47) that specifically
      bound to the EGFRvIII-overexpressing human glioma U87Delta cells with Kd values
      of less than 100 nmol/L were discovered. These aptamers were able to distinguish
      the U87Delta cells from the negative control human glioma U87MG cells and HEK293
      cells. Aptamer 32 specifically bound to the EGFRvIII protein with an affinity
      similar to the EGFR antibody (Kd values of aptamer 32 and the EGFR antibody were
      0.62+/-0.04 and 0.32+/-0.01 nmol/L, respectively), and this aptamer was localized
      in the cell nucleus. CONCLUSION: The DNA aptamers are promising molecular probes
      for the diagnosis and treatment of GBM.

PMID- 24304920
TI  - Molecular modeling, quantum polarized ligand docking and structure-based 3D-QSAR
      analysis of the imidazole series as dual AT(1) and ET(A) receptor antagonists.
AB  - AIM: Both endothelin ETA receptor antagonists and angiotensin AT1 receptor
      antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA
      receptor antagonist may be more efficacious antihypertensive drug. In this study
      we identified the mode and mechanism of binding of imidazole series of compounds
      as dual AT1 and ETA receptor antagonists. METHODS: Molecular modeling approach
      combining quantum-polarized ligand docking (QPLD), MM/GBSA free-energy
      calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1
      and ETA receptor antagonists and to reveal their binding modes and structural
      basis of the inhibitory activity. Pharmacophore-based virtual screening and
      docking studies were performed to identify more potent dual antagonists. RESULTS:
      3D-QSAR models of the imidazole compounds were developed from the conformer
      generated by QPLD, and the resulting models showed a good correlation between the
      predicted and experimental activity. The visualization of the 3D-QSAR model in
      the context of the compounds under study revealed the details of the structure
      activity relationship: substitution of methoxymethyl and cyclooctanone might
      increase the activity against AT1 receptor, while substitution of cyclohexone and
      trimethylpyrrolidinone was important for the activity against ETA receptor;
      addition of a trimethylpyrrolidinone to compound 9 significantly reduced its
      activity against AT1 receptor but significantly increased its activity against
      ETA receptor, which was likely due to the larger size and higher intensities of
      the H-bond donor and acceptor regions in the active site of ETA receptor.
      Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD
      and MM/GBSA calculation identified 5 potential lead compounds that might act as
      dual AT1 and ETA receptor antagonists. CONCLUSION: This study may provide some
      insights into the development of novel potent dual ETA and AT1 receptor
      antagonists. As a result, five compounds are found to be the best dual
      antagonists against AT1R and ETA receptors.

PMID- 24304921
TI  - Health state utilities in patients with diabetic retinopathy, diabetic macular
      oedema and age-related macular degeneration: a systematic review.
AB  - BACKGROUND: Health state utility values (HSUVs) are important in the assessment
      of the cost effectiveness of new interventions. In the case of visual conditions,
      models generally tend have tended to be built around a set of health states
      defined by visual acuity (VA). The aim of this review was to assess the impact of
      VA on HSUVs in patients with diabetic retinopathy, diabetic macular oedema or age
      related macular degeneration. METHODS: A systematic literature search was
      undertaken in major bibliographic databases to identify articles reporting on the
      relationship between HSUVs and vision. Data were extracted for population
      characteristics, visual levels and estimated utilities. Evidence from reported
      statistical models, where available, was considered in the evaluation of vision
      in the better-seeing eye and the worse-seeing eye. Due to the heterogeneity of
      included studies, a narrative synthesis was undertaken. RESULTS: Of the 17
      relevant studies, 9 studies had data that could be used in the analysis of the
      impact of vision on HSUVs. Visual loss was associated with a marked impact on
      health utilities. However, the relationship was not comparable between conditions
      or by measure of HSUVs. Key results included the finding that overall, self-rated
      time-trade off estimates were more likely to discriminate between different VA
      levels than EQ-5D values. Additionally, a stronger correlation was observed
      between HSUVs and better-seeing eye VA compared to worse-seeing eye VA.
      CONCLUSIONS: Visual acuity has a significant impact on HSUVs. Nevertheless, care
      must be taken in the interpretation and use of estimates in cost-effectiveness
      models due to differences in measures and population diversity.

PMID- 24304922
TI  - Genomic effects on advertisement call structure in diploid and triploid hybrid
      waterfrogs (Anura, Pelophylax esculentus).
AB  - BACKGROUND: In anurans, differences in male mating calls have intensively been
      studied with respect to taxonomic classification, phylogeographic comparisons
      among different populations and sexual selection. Although overall successful,
      there is often much unexplained variation in these studies. Potential causes for
      such variation include differences among genotypes and breeding systems, as well
      as differences between populations. We investigated how these three factors
      affect call properties in male water frogs of Pelophylax lessonae (genotype LL),
      P. ridibundus (RR) and their interspecific hybrid P. esculentus which comes in
      diploid (LR) and triploid types (LLR, LRR). RESULTS: We investigated five call
      parameters that all showed a genomic dosage effect, i.e. they either decreased or
      increased with the L/R ratio in the order LL-LLR-LR-LRR-RR. Not all parameters
      differentiated equally well between the five genotypes, but combined they
      provided a good separation. Two of the five call parameters were also affected by
      the breeding system. Calls of diploid LR males varied, depending on whether these
      males mated with one or both of the parental species (diploid systems) or
      triploid hybrids (mixed ploidy systems). With the exception of the northernmost
      mixed-ploidy population, call differences were not related to the geographic
      location of the population and they were not correlated with genetic distances in
      the R and L genomes. CONCLUSIONS: We found an influence of all three tested
      factors on call parameters, with the effect size decreasing from genotype through
      breeding system to geographic location of the population. Overall, results were
      in line with predictions from a dosage effect in L/R ratios, but in three call
      parameters all three hybrid types were more similar to one or the other parental
      species. Also calls of diploid hybrids varied between breeding systems in
      agreement with the sexual host required for successful reproduction. The lack of
      hybrid call differences in a mixed-ploidy population at the northern edge of the
      water frog distribution is likely to be associated with genetic particularities,
      including a) low genetic variability and/or b) a local loss of genes coding for
      genotype-dependent call differentiation under conditions where female
      discrimination between diploid and triploid males is not beneficial.

PMID- 24304923
TI  - Simultaneous inbreeding modifies inbreeding depression in a plant-herbivore
      interaction.
AB  - Because inbreeding is common in natural populations of plants and their
      herbivores, herbivore-induced selection on plants, and vice versa, may be
      significantly modified by inbreeding and inbreeding depression. In a feeding
      assay with inbred and outbred lines of both the perennial herb, Vincetoxicum
      hirundinaria, and its specialist herbivore, Abrostola asclepiadis, we discovered
      that plant inbreeding increased inbreeding depression in herbivore performance in
      some populations. The effect of inbreeding on plant resistance varied among plant
      and herbivore populations. The among-population variation is likely to be driven
      by variation in plant secondary compounds across populations. In addition,
      inbreeding depression in plant resistance was substantial when herbivores were
      outbred, but diminished when herbivores were inbred. These findings demonstrate
      that in plant-herbivore interactions expression of inbreeding depression can
      depend on the level of inbreeding of the interacting species. Furthermore, our
      results suggest that when herbivores are inbred, herbivore-induced selection
      against self-fertilisation in plants may diminish. 

PMID- 24304924
TI  - Foods with added fiber improve stool frequency in individuals with chronic kidney
      disease with no impact on appetite or overall quality of life.
AB  - BACKGROUND: Fiber intake may be low in individuals with chronic kidney disease
      (CKD) due to diet restriction and/or poor appetite associated with uremic
      symptoms, contributing to constipation and reduced quality of life. This report
      describes the effects of foods with added fiber on gastrointestinal function and
      symptoms, clinical markers, and quality of life in CKD patients. FINDINGS: Adults
      with CKD (n = 15; 9 F, 6 M; 66 +/- 15 y) were provided with cereal, cookies and
      snack bars without added fiber for 2 weeks, followed by similar foods providing
      23 g/d of added fiber for 4 weeks, to incorporate into their usual diets.
      Participants completed the Kidney Disease Quality of Life (KDQOL-36)
      questionnaire, the Simplified Nutritional Appetite Questionnaire (SNAQ) and the
      Epworth Sleepiness Scale (ESS) bi-weekly, the Gastrointestinal Symptom Rating
      Scale (GSRS) weekly, and daily stool frequency and compliance. Control and
      intervention serum cholesterol and glucose were assessed. Providing 23 g/d of
      added fiber increased stool frequency (1.3 +/- 0.2 to 1.6 +/- 0.2 stools/d; P =
      0.02), decreased total cholesterol (175 +/- 12 to 167 +/- 11 mg/dL; P = 0.02) and
      improved TC:HDL ratio (4.0 +/- 0.3 to 3.7 +/- 0.2; P = 0.02). GSRS and SNAQ
      scores did not change, but SNAQ scores suggested poor appetite in 7 participants
      with or without added fiber. KDQOL Mental Health Composite decreased from 53 +/-
      2 to 48 +/- 2 (P = 0.01) while Physical Health Composite increased from 31 +/- 2
      to 35 +/- 3 (P = 0.02), with no change in overall QOL. The ESS score decreased
      from 10 +/- 1 to 8 +/- 1 (P = 0.04). CONCLUSION: Consuming foods with added fiber
      may be an effective means of increasing fiber intakes, improving stool frequency,
      and lipid profile in individuals with CKD. TRIAL REGISTRATION:
      ClinicalTrials.gov, # NCT01842087.

PMID- 24304925
TI  - Rapid decline in bone turnover markers but not bone mineral density in
      acromegalic patients after transsphenoidal surgery.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play important roles
      in maintaining bone metabolism and bone mineral density (BMD) in adulthood, in
      addition to stimulating longitudinal bone growth in childhood. However,
      information on the effect of GH excess on bone metabolism and BMD is incomplete
      and requires further analysis. The aim of this study is to clarify the effect of
      rapid decline in GH levels after transsphenoidal surgery (TSS) on bone metabolism
      in acromegalic patients. In this prospective study, 22 patients (11 males and 11
      females) with active acromegaly underwent TSS. Bone formation marker (serum bone
      alkaline phosphatase: BAP), bone resorption marker (urinary type I collagen cross
      linked N-telopeptide: urinary NTx) and BMD were measured before and at 3 and 12
      months after TSS. BAP was significantly decreased at 12 months after TSS, but not
      at 3 months. Urinary NTx was significantly decreased at 3 and 12 months after
      TSS. BMD did not change after TSS. In conclusion, the rapid fall in GH level
      after TSS had no effect on BMD for up to 12 months after TSS despite the decrease
      in markers of bone formation and resorption. 

PMID- 24304926
TI  - The role of in vivo confocal microscopy in the diagnosis of hidden corneal
      foreign bodies.
AB  - OBJECTIVE: To investigate in vivo confocal microscopy (IVCM) to diagnose hidden
      corneal foreign bodies. METHODS: Male Kunming mice (n = 25; 12 weeks old) were
      anaesthetized prior to the insertion of five different materials (spiny wood,
      rusty iron, sharp stone, sharp glass fragment and human hair fragment) into the
      cornea by different traumatic processes. A separate mouse was used for each
      corneal foreign body. The corneas of the mice were scanned 24 h later by a laser
      scanning IVCM to establish the characteristics (shape, reflectivity and depth in
      the cornea) of each foreign body. These findings were used to help screen and
      identify corneal foreign bodies in patients. Corneal smears and scraping cultures
      were performed in cases of probable corneal infection. RESULTS: Animal models for
      the five different foreign particles were established successfully, with each
      showing distinctive characteristics. These animal results were used to diagnose
      41 patients with suspected corneal foreign bodies who were negative by slit lamp
      examination, but positive by IVCM (observational case series). The most prevalent
      type of hidden foreign body was plant material (51.2%), followed by metal
      (29.3%). Ten patients with corneal foreign bodies developed fungal keratitis,
      found using IVCM. CONCLUSIONS: Laser IVCM is an effective and reliable tool for
      the diagnosis of hidden corneal foreign bodies.

PMID- 24304927
TI  - A preliminary association study of fat mass and obesity associated gene
      polymorphisms and degenerative disc disease in a Chinese Han population.
AB  - OBJECTIVE: To assess whether polymorphisms of the fat mass and obesity associated
      gene (FTO) are associated with the presence and severity of degenerative disc
      disease (DDD) in a Chinese Han population. METHODS: In this case-control study,
      patients with DDD and controls matched for age, sex and body mass index were
      genotyped for six single nucleotide polymorphisms (SNPs) of FTO. Disease severity
      was measured using the Japanese Orthopaedic Association score. Allelic, genotypic
      and genotype-phenotype association analyses were performed. RESULTS: A total of
      80 patients with DDD and 80 controls were studied. All six SNPs were in Hardy
      Weinberg equilibrium. The frequencies of allele G and genotype G/G of the SNP
      rs11076008 were significantly associated with DDD after Bonferroni correction. No
      associations were shown between the SNPs studied and sex or disease severity.
      CONCLUSION: The SNP rs11076008 of FTO may play an important role in the
      development of DDD in a Chinese Han population. The G/G genotype and/or G allele
      may be a risk factor for DDD. These results suggest that FTO is a DDD
      predisposition gene and may support a close relationship between obesity and DDD.

PMID- 24304929
TI  - Leukemia cells induce changes in human bone marrow stromal cells.
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) are multipotent cells that support
      angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche,
      they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete
      of a wide range of cytokines, growth factors and matrix proteins which contribute
      to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN
      gamma and TNF-alpha change the BMSC secretome and we hypothesized that factors
      produced by tumors or leukemia would also affect the BMSC secretome and
      investigated the interaction of leukemia cells with BMSCs. METHODS: BMSCs from
      healthy subjects were co-cultured with three myeloid leukemia cell lines (TF-1,
      TF-1alpha and K562) using a trans-well system. Following co-culture, the BMSCs
      and leukemia cells were analyzed by global gene expression analysis and culture
      supernatants were analyzed for protein expression. As a control, CD34+ cells were
      also cocultured with BMSCs. RESULTS: Co-culture induced leukemia cell gene
      expression changes in stem cell pluripotency, TGF-beta signaling and carcinoma
      signaling pathways. BMSCs co-cultured with leukemia cells up-regulated a number
      of proinflammatory genes including IL-17 signaling-related genes and IL-8 and
      CCL2 levels were increased in co-culture supernatants. In contrast, purine
      metabolism, mTOR signaling and EIF2 signaling pathways genes were up-regulated in
      BMSCs co-cultured with CD34+ cells. CONCLUSIONS: BMSCs react to the presence of
      leukemia cells undergoing changes in the cytokine and chemokine secretion
      profiles. Thus, BMSCs and leukemia cells both contribute to the creation of a
      competitive niche more favorable for leukemia stem cells.

PMID- 24304930
TI  - The P2 of Wheat yellow mosaic virus rearranges the endoplasmic reticulum and
      recruits other viral proteins into replication-associated inclusion bodies.
AB  - Viruses commonly modify host endomembranes to facilitate biological processes in
      the viral life cycle. Infection by viruses belonging to the genus Bymovirus
      (family Potyviridae) has long been known to induce the formation of large
      membranous inclusion bodies in host cells, but their assembly and biological
      roles are still unclear. Immunoelectron microscopy of cells infected with the
      bymovirus Wheat yellow mosaic virus (WYMV) showed that P1, P2 and P3 are the
      major viral protein constituents of the membranous inclusions, whereas NIa-Pro
      (nuclear inclusion-a protease) and VPg (viral protein genome-linked) are probable
      minor components. P1, P2 and P3 associated with the endoplasmic reticulum (ER),
      but only P2 was able to rearrange ER and form large aggregate structures.
      Bioinformatic analyses and chemical experiments showed that P2 is an integral
      membrane protein and depends on the active secretory pathway to form aggregates
      of ER membranes. In planta and in vitro assays demonstrated that P2 interacts
      with P1, P3, NIa-Pro or VPg and recruits these proteins into the aggregates. In
      vivo RNA labelling using WYMV-infected wheat protoplasts showed that the
      synthesis of viral RNAs occurs in the P2-associated inclusions. Our results
      suggest that P2 plays a major role in the formation of membranous compartments
      that house the genomic replication of WYMV.

PMID- 24304931
TI  - Lowered cancer risk with ACE inhibitors/ARBs: a population-based cohort study.
AB  - There are conflicting reports on cancer risk associated with angiotensin
      converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). This
      retrospective cohort study was conducted to analyze the risk of cancer
      development in patients who received ACE inhibitors/ARBs as treatment for
      essential hypertension. Using the Taiwan National Health Insurance Research
      Database, 297,688 eligible study patients with essential hypertension were
      identified. According to their antihypertensive prescriptions, the study patients
      were stratified into an ACE inhibitor group, an ARB group, or a control group.
      After matching, participants were observed for the occurrence of cancer. In the
      ACE inhibitor group compared with the control group, the hazard ratio was 0.51
      (95% confidence interval, 0.39-0.68). In the ARB group compared with the control
      group, the hazard ratio was 0.8 (95% confidence interval, 0.65-0.97). Regular use
      of ACE inhibitors/ARBs was not associated with an increased risk of cancer
      development and was actually found to decrease overall cancer risk in this study.

PMID- 24304932
TI  - Formaldehyde-associated changes in microRNAs: tissue and temporal specificity in
      the rat nose, white blood cells, and bone marrow.
AB  - MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains
      unknown regarding their changes resulting from environmental exposures as they
      influence cellular signaling across various tissues. We set out to investigate
      miRNA responses to formaldehyde, a critical air pollutant and known carcinogen
      that disrupts miRNA expression profiles. Rats were exposed by inhalation to
      either 0 or 2 ppm formaldehyde for 7, 28, or 28 days followed by a 7-day
      recovery. Genome-wide miRNA expression profiles were assessed within the nasal
      respiratory epithelium, circulating white blood cells (WBC), and bone marrow
      (BM). miRNAs showed altered expression in the nose and WBC but not in the BM.
      Notably in the nose, miR-10b and members of the let-7 family, known
      nasopharyngeal carcinoma players, showed decreased expression. To integrate miRNA
      responses with transcriptional changes, genome-wide messenger RNA profiles were
      assessed in the nose and WBC. Although formaldehyde-induced changes in miRNA and
      transcript expression were largely tissue specific, pathway analyses revealed an
      enrichment of immune system/inflammation signaling in the nose and WBC. Specific
      to the nose was enrichment for apoptosis/proliferation signaling, involving let
      7a, let-7c, and let-7f. Across all tissues and time points assessed, miRNAs were
      predicted to regulate between 7% and 35% of the transcriptional responses and
      were suggested to play a role in signaling processes including
      immune/inflammation-related pathways. These data inform our current hypothesis
      that formaldehyde-induced inflammatory signals originating in the nose may drive
      WBC effects. 

PMID- 24304933
TI  - Investigating individual arsenic dopant atoms in silicon using low-temperature
      scanning tunnelling microscopy.
AB  - We study subsurface arsenic dopants in a hydrogen-terminated Si(001) sample at 77
      K, using scanning tunnelling microscopy and spectroscopy. We observe a number of
      different dopant-related features that fall into two classes, which we call As1
      and As2. When imaged in occupied states, the As1 features appear as anisotropic
      protrusions superimposed on the silicon surface topography and have maximum
      intensities lying along particular crystallographic orientations. In empty-state
      images the features all exhibit long-range circular protrusions. The images are
      consistent with buried dopants that are in the electrically neutral (D0) charge
      state when imaged in filled states, but become positively charged (D+) through
      electrostatic ionization when imaged under empty-state conditions, similar to
      previous observations of acceptors in GaAs. Density functional theory
      calculations predict that As dopants in the third layer of the sample induce two
      states lying just below the conduction-band edge, which hybridize with the
      surface structure creating features with the surface symmetry consistent with our
      STM images. The As2 features have the surprising characteristic of appearing as a
      protrusion in filled-state images and an isotropic depression in empty-state
      images, suggesting they are negatively charged at all biases. We discuss the
      possible origins of this feature.

PMID- 24304934
TI  - The role of focal adhesion kinase in the regulation of cellular mechanical
      properties.
AB  - The regulation of mechanical properties is necessary for cell invasion into
      connective tissue or intra- and extravasation through the endothelium of blood or
      lymph vessels. Cell invasion is important for the regulation of many healthy
      processes such as immune response reactions and wound healing. In addition, cell
      invasion plays a role in disease-related processes such as tumor metastasis and
      autoimmune responses. Until now the role of focal adhesion kinase (FAK) in
      regulating mechanical properties of cells and its impact on cell invasion
      efficiency is still not well known. Thus, this review focuses on mechanical
      properties regulated by FAK in comparison to the mechano-regulating protein
      vinculin. Moreover, it points out the connection between cancer cell invasion and
      metastasis and FAK by showing that FAK regulates cellular mechanical properties
      required for cellular motility. Furthermore, it sheds light on the indirect
      interaction of FAK with vinculin by binding to paxillin, which then impairs the
      binding of paxillin to vinculin. In addition, this review emphasizes whether FAK
      fulfills regulatory functions similar to vinculin. In particular, it discusses
      the differences and the similarities between FAK and vinculin in regulating the
      biomechanical properties of cells. Finally, this paper highlights that both focal
      adhesion proteins, vinculin and FAK, synergize their functions to regulate the
      mechanical properties of cells such as stiffness and contractile forces.
      Subsequently, these mechanical properties determine cellular invasiveness into
      tissues and provide a source sink for future drug developments to inhibit
      excessive cell invasion and hence, metastases formation. 

PMID- 24304935
TI  - Discovery of the neuroprotective effects of alvespimycin by computational
      prioritization of potential anti-Parkinson agents.
AB  - Based on public gene expression data, we propose a computational approach to
      optimize gene expression signatures for the use with Connectivity Map (CMap) to
      reposition drugs or discover lead compounds for Parkinson's disease. This
      approach integrates genetic information from the Gene Expression Omnibus (GEO)
      database, the Parkinson's disease gene expression database (ParkDB), the Online
      Mendelian Inheritance in Man (OMIM) database and the Comparative Toxicogenomics
      Database (CTD), with the aim of identifying a set of interesting genes for use in
      computational drug screening via CMap. The results showed that CMap, using the
      top 20 differentially expressed genes identified by our approach as a gene
      expression signature, outperformed the same method using all differentially
      expressed genes (n = 535) as a signature. Utilizing this approach, the candidate
      compound alvespimycin (17-DMAG) was selected for experimental evaluation in a
      model of rotenone-induced toxicity in human SH-SY5Y neuroblastoma cells and
      isolated rat brain mitochondria. The results showed that 17-DMAG significantly
      attenuated rotenone-induced toxicity, as reflected by the increase of cell
      viability, the reduction of intracellular reactive oxygen species generation and
      a reduction in mitochondrial respiratory dysfunction. In conclusion, this
      computational method provides an effective systematic approach for drug
      repositioning or lead compound discovery for Parkinson's disease, and the
      discovery of the neuroprotective effects of 17-DMAG supports the practicability
      of this method.

PMID- 24304936
TI  - Region and boundary feature estimation on ultrasound images using moment
      invariants.
AB  - In ultrasound images, tissues are characterized by their speckle texture. Moment
      based techniques have proven their ability to capture texture features. However,
      in ultrasound images, the speckle size increases with the distance from the probe
      and in some cases the speckle has a concentric texture arrangement. We propose to
      use moment invariants with respect to image scale and rotation to capture the
      texture in such cases. Results on synthetic data show that moment invariants are
      able to characterize the texture but also that some moment orders are sensitive
      to regions and, moreover, some are sensitive to the boundaries between two
      different textures. This behavior seems to be very interesting to be used within
      some segmentation scheme dealing with a combination of regional and boundary
      information. In this paper we will try to prove the usability of this
      complementary information in a min-cut/max-flow graph cut scheme. 

PMID- 24304937
TI  - The DNA double-strand break response is abnormal in myeloblasts from patients
      with therapy-related acute myeloid leukemia.
AB  - The complex chromosomal aberrations found in therapy-related acute myeloid
      leukemia (t-AML) suggest that the DNA double-strand break (DSB) response may be
      altered. In this study we examined the DNA DSB response of primary bone marrow
      cells from t-AML patients and performed next-generation sequencing of 37
      canonical homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA
      repair genes, and a subset of DNA damage response genes using tumor and paired
      normal DNA obtained from t-AML patients. Our results suggest that the majority of
      t-AML patients (11 of 15) have tumor-cell intrinsic, functional dysregulation of
      their DSB response. Distinct patterns of abnormal DNA damage response in
      myeloblasts correlated with acquired genetic alterations in TP53 and the presence
      of inferred chromothripsis. Furthermore, the presence of trisomy 8 in tumor cells
      was associated with persistently elevated levels of DSBs. Although tumor-acquired
      point mutations or small indels in canonical HR and NHEJ genes do not appear to
      be a dominant means by which t-AML leukemogenesis occurs, our functional studies
      suggest that an abnormal response to DNA damage is a common finding in t-AML. 

PMID- 24304938
TI  - Relationship between galectin-3 levels and mineralocorticoid receptor antagonist
      use in heart failure: analysis from HF-ACTION.
AB  - BACKGROUND: Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated
      levels are associated with adverse outcomes. Mineralocorticoid receptor
      antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and
      have been shown to improve long-term outcomes. We examined whether treatment
      effects from MRA use differed by Gal-3 levels in ambulatory heart failure
      patients enrolled in HF-ACTION. METHODS AND RESULTS: HF-ACTION was a randomized
      controlled trial of exercise training versus usual care in patients with HF due
      to LV systolic dysfunction (New York Heart Association functional class II-IV,
      left ventricular ejection fraction <= 0.35, median follow-up 2.5 years). Galectin
      3 was assessed at baseline in 895 patients. The end point was all-cause mortality
      or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key
      secondary end point. A differential association of MRA use by increasing Gal-3
      concentration was tested with the use of interaction terms in Cox proportional
      hazards models, adjusted for covariates previously identified in this cohort as
      well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also
      used to assess this association. Approximately one-half (n = 401) of the patients
      were on an MRA. There was no significant interaction for the associations of Gal
      3 levels and MRA use for either end point (adjusted interaction P = .76 for
      ACM+ACH; P = .26 for ACM). There was no evidence of improved outcomes for
      patients on an MRA compared with those not on MRA for either end point (hazard
      ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P = .8; and HR = 1.15,
      95% CI [0.82-1.61], P = .4; respectively). IPW analysis was consistent with the
      results of the adjusted analysis. CONCLUSION: Our study showed no evidence of
      interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be
      used to predict which patients may benefit from an mineralocorticoid receptor
      antagonist in HF requires further investigation.

PMID- 24304939
TI  - Relative clause constructions in children with specific language impairment.
AB  - BACKGROUND: It is well documented that children with specific language impairment
      (SLI) experience significant grammatical deficits. While much of the focus in the
      past has been on morphosyntactic difficulties, less is known about their
      acquisition of multi-clausal constructions such as those containing relative
      clauses. AIMS: To investigate relative clause constructions in English-speaking,
      school-aged children with SLI using a sentence-recall task. METHODS & PROCEDURES:
      Children with SLI (mean age = 6;10; n = 32) and two control groups, a typically
      developing group matched for age (AM-TD; mean age = 6;11; n = 32) and a younger
      typically developing group (YTD; mean age = 4;9; n = 20), repeated sentences that
      contained relative clauses which represented a range of syntactic roles. The
      relative clauses were attached either to the predicate nominal of a copular
      clause or to the direct object of a transitive clause. OUTCOMES & RESULTS:
      Children with SLI showed significantly greater difficulty than both the AM-TD and
      the YTD groups overall, but found some relative clause types easier than others,
      displaying a similar profile to typically developing children but at a lower
      level of performance. CONCLUSIONS & IMPLICATIONS: Children with SLI who are close
      to 7 years of age have significantly greater difficulty with relative clauses
      than their age peers and typically developing children who are on average 2 years
      younger. Their performance is influenced by the matrix clause type, the role of
      the relativized element within the relative clause, and in object relative
      clauses, lexical choices within the matrix clause and the relative clause.

PMID- 24304940
TI  - Validation of a new bowel preparation scale for measuring colon cleansing for
      colonoscopy: the chicago bowel preparation scale.
AB  - OBJECTIVES: Current bowel preparation scales (BPSs) have significant limitations
      including an inability to distinguish among bowel preparations that adequately
      cleanse a high percentage of colons. We assessed the reliability and validity of
      the new Chicago BPS and compared it with existing BPSs. METHODS: We performed a
      prospective evaluation of the cleanliness of 150 colons. Inter-rater agreement
      was assessed using kappa and Pearson correlation coefficients. Each colon was
      rated by a gastroenterologist and physician's assistant using the Ottawa BPS, the
      Boston BPS, a dichotomous (adequate/inadequate) BPS (where adequate was defined
      as being able to visualize at least 95% of the mucosa), and the Chicago BPS.
      RESULTS: Pearson correlation coefficients between the gastroenterologists and
      physician's assistant for total BPS scores were 0.79 (95% confidence interval
      (CI): 0.73, 0.85), 0.79 (95% CI: 0.72, 0.84), and 0.84 (95% CI: 0.79, 0.88) for
      the Ottawa, Boston, and Chicago BPSs, respectively. Kappa coefficients for right,
      middle, and distal colon segment ratings were 0.66, 0.53, and 0.49, respectively,
      for the Ottawa BPS; 0.64, 0.66, and 0.54, respectively, for the Boston BPS; and
      0.70, 0.62, and 0.63, respectively, for the Chicago BPS. Differences between the
      Chicago BPS and the other BPSs were not statistically significant. The Chicago
      BPS exhibited the best correspondence between BPS total score and the
      adequate/inadequate BPS. CONCLUSIONS: This study demonstrated the validity and
      reliability of the Chicago BPS. The better defined grading criteria, better
      designed numerical ratings scale, and better correspondence between Chicago BPS
      total score and the adequate/inadequate BPS make the Chicago BPS an attractive
      alternative to the Ottawa BPS and the Boston BPS.

PMID- 24304941
TI  - BioVector, a flexible system for gene specific-expression in plants.
AB  - BACKGROUND: Functional genomic research always needs to assemble different DNA
      fragments into a binary vector, so as to express genes with different tags from
      various promoters with different levels. The cloning systems available bear
      similar disadvantages, such as promoters/tags are fixed on a binary vector, which
      is generally with low cloning efficiency and limited for cloning sites if a novel
      promoter/tag is in need. Therefore, it is difficult both to assemble a gene and a
      promoter together and to modify the vectors in hand. Another disadvantage is that
      a long spacer from recombination sites, which may be detrimental to the protein
      function, exists between a gene and a tag. Multiple GATEWAY system only resolves
      former problem at the expense of very low efficiency and expensive for multiple
      LR reaction. RESULTS: To improve efficiency and flexibility for constructing
      expression vectors, we developed a platform, BioVector, by combining classical
      restriction enzyme/ligase strategy with modern Gateway DNA recombination system.
      This system included a series of vectors for gene cloning, promoter cloning, and
      binary vector construction to meet various needs for plant functional genomic
      study. CONCLUSION: This BioVector platform makes it easy to construct any vectors
      to express a target gene from a specific promoter with desired intensity, and it
      is also waiting to be freely modified by researchers themselves for ongoing
      demands. This idea can also be transferred to the different fields including
      animal or yeast study.

PMID- 24304942
TI  - A survey of parentally reported sleep health disorders in Estonian 8-9 year old
      children.
AB  - BACKGROUND: Pediatric sleep research is rather new in Estonia. There has not been
      a comprehensive study of age specific sleep disorders in Estonian children. The
      aim of this study was to investigate sleep disorders in a sample of Estonian
      second grade children.We hypothesized that:: Children with low BMI are as
      susceptible to SDB as are children with high BMI. Under weight children are
      susceptible to residual SDB after adenotonsillectomy. Parasomnias present with
      SDB in children.* Excessive day time sleepiness is a significant symptom which
      leads parents to suspect sleep disorders in their child. METHODS: A retrospective
      questionnaire based survey was used to analyze factors influencing sleep,
      parasomnias, daytime sleepiness, and sleep disordered breathing (SDB). 1065
      Pediatric Sleep Questionnaire (PSQ) packets were distributed by post to randomly
      selected parents of second grade students; 703 (66%) subjects were included in
      the study group; each parent/guardian participant had one second grade child.
      Descriptive statistics were used to compare characteristics of SDB symptomatic
      and healthy children. We used logistic regression to analyze factors influencing
      sleep and parasomnias in relation to SDB severity. Odds ratios (OR) and 95% CI
      were used to estimate relative risk. RESULTS: Parents of children with SDB
      complaints seem to pay attention to sleep disorders especially when a child is
      suffering from excessive day time sleepiness. Parasomnias are present
      simultaneously with SDB and tend to worsen in relation to more severe SDB
      complaints. Many underweight children have SDB symptoms after adenotonsillectomy.
      CONCLUSION: SDB symptoms are found in both overweight and underweight children.
      Both groups should be observed, especially in terms of the current focus on
      overweight children. Careful follow up after SDB treatment is necessary in case
      of under and overweight children. Parental suspicions regarding SDB are
      noticeably higher in cases of excessive daytime sleepiness in their children.

PMID- 24304943
TI  - The effect of metritis on luteal function in dairy cows.
AB  - BACKGROUND: Disturbed uterine involution impairs ovarian function in the first
      weeks after calving. This study analyzed the long-term effect of metritis on
      luteal function of 47 lactating Holstein-Friesian cows during the first four
      postpartum estrous cycles. Cows with abnormal uterine enlargement and malodorous
      lochia were classified as having metritis (group M, n = 18), and all others were
      considered healthy (group H, n = 29). Luteal size was measured once between days
      9 and 13 of the first (group H, n = 11; group M, n = 12), second (group H, n =
      23; group M, n = 18) and fourth (group H, n = 11; group M, n = 7) postpartum
      luteal phases. Serum progesterone concentration was measured at the same time.
      Sixteen cows (group H, n = 9; group M, n = 7) underwent transvaginal luteal
      biopsy for gene expression analysis of steroidogenic regulatory proteins during
      the second and fourth cycles. Cows with persistence of the corpus luteum (CL)
      underwent determination of luteal size, luteal biopsy and serum progesterone
      measurement once between days 29 and 33, followed by prostaglandin treatment to
      induce luteolysis. The same procedures were repeated once between days 9 and 13
      of the induced cycle. RESULTS: The cows in group M had smaller first-cycle CLs
      than the cows in group H (p = 0.04), but progesterone concentrations did not
      differ between groups. Luteal size, progesterone concentration and gene
      expression did not differ between the two groups during the second and fourth
      cycles. Compared with healthy cows (10%), there was a trend (p = 0.07) toward a
      higher prevalence of persistent CLs in cows with metritis (33%). Persistent CLs
      were limited to the first cycle. Persistent CLs and the induced cyclic CLs did
      not differ with regard to the variables investigated. CONCLUSIONS: An effect of
      metritis on luteal activity was apparent in the first postpartum estrous cycle.
      However, after the first postpartum cycle, no differences occurred in analyzed
      parameters between metritis and control cows. Therefore, a metritis is able to
      impair luteal activity transiently, but does not seem to have a long-term effect
      on luteal function.

PMID- 24304944
TI  - Sensitivity of a point of care tick-test for the development of Lyme borreliosis.
AB  - BACKGROUND: A commercially available self-test for the detection of Borrelia
      burgdorferi sensu lato in ticks was evaluated for its ability to predict erythema
      migrans formation. FINDINGS: The self-test was performed on 127 Ixodes ricinus
      from 122 humans that reported tick bites at enrolment and occurrence of symptoms
      during follow-up. The self-test gave negative results on all the 122 individuals,
      14 of whom reported erythema migrans (EM) at follow-up of which 10 were confirmed
      by their GP. The estimated sensitivity of the self-test for prediction of EM
      formation is 0% (95% CI: 0%-28%). CONCLUSIONS: This self-test is not suitable for
      reducing the number needed to treat in a post-exposure prophylaxis setting as it
      already missed all the obvious early Lyme borreliosis cases.

PMID- 24304945
TI  - Trends and determinants of mortality in women of reproductive age in rural Guinea
      Bissau, West Africa--a cohort study.
AB  - BACKGROUND: There are few studies reporting mortality of women of reproductive
      age (WRA) in developing countries. The trend and patterns of their mortality may
      be important for documenting the health status of the population in general.
      METHODS: We used a prospective open cohort of women aged 12 to 49 years living in
      the Bandim Health Project's rural Health and Demographic Surveillance System
      (HDSS) in 5 regions of Guinea-Bissau from 1996 to 2007. Information on in- and
      out-migration and deaths were collected through the HDSS routine procedures. We
      assessed the trends in mortality and the associated determinants using Cox
      regression models. RESULTS: We followed 27,185 WRA for 141,693 person-years-at
      risk (PYO) among whom 9,093 moved out and 1,006 died. Overall standardized
      mortality rate was 759 per 100,000 PYO. WRA mortality did not decline, but three
      periods could be distinguished: a stable mortality between 1996-2000 followed by
      14% increase in mortality [Hazard rate ratio (HRR) = 1.14; 95% confidence
      interval (CI): 0.98-1.32; p = 0.08] between 2001-2003, and then in the last
      period from 2004-2007 a 25% decline (HRR = 0.75; 95% CI: 0.64-0.87; p < 0.001) in
      relation to the first period. Compared with the years 1990-1996 mortality
      increased in the first two periods until 2003; only in the last period did
      mortality reach the same level as in 1990-1996 (HRR = 0.96; 95% CI: 0.82-1.13; p
      = 0.62). The level of mortality differed between regions. In the adjusted
      analysis the eastern regions Bafata (HRR = 1.79; 95% CI: 1.38-2.32; p < 0.001)
      and Gabu (HRR = 1.70; 95% CI: 1.28-2.26; p < 0.001) had significantly higher
      mortality, but the hazard rate did not differ by ethnic group. As expected the
      rate increased with increasing age. CONCLUSIONS: Over the twelve-year period
      mortality of WRA did not decline. A stable mortality in the beginning was
      followed by an increase and then a return to the previous levels. Further
      monitoring of mortality is needed to identify the risk factors for the striking
      regional differences. Advantage should be taken of the HDSS to monitor progress
      towards the MDGs and beyond.

PMID- 24304946
TI  - Predicting the process of extinction in experimental microcosms and accounting
      for interspecific interactions in single-species time series.
AB  - Predicting population extinction risk is a fundamental application of ecological
      theory to the practice of conservation biology. Here, we compared the prediction
      performance of a wide array of stochastic, population dynamics models against
      direct observations of the extinction process from an extensive experimental data
      set. By varying a series of biological and statistical assumptions in the
      proposed models, we were able to identify the assumptions that affected
      predictions about population extinction. We also show how certain autocorrelation
      structures can emerge due to interspecific interactions, and that accounting for
      the stochastic effect of these interactions can improve predictions of the
      extinction process. We conclude that it is possible to account for the stochastic
      effects of community interactions on extinction when using single-species time
      series. 

PMID- 24304947
TI  - [Discussion on the strategy of prevention and control of pancreatic cancer].

PMID- 24304948
TI  - [Incidence and mortality of oral cavity and pharyngeal cancer in China, 2009].
AB  - OBJECTIVE: To analyze the incidence and mortality of oral cavity and pharyngeal
      cancer in cancer-registration areas of China in 2009. METHODS: We collected data
      about incidence of oral cavity and pharyngeal from 72 cancer registry sites of
      National Central Registry Database in 2009, covering 85 470 522 person (57 489
      009 were from urban areas, 27 981 513 were from rural areas).Incidence and
      mortality rates, proportions, cumulative rate (0-74 years old), cut rate (35-64
      years old), age-specific rate were then calculated and analyzed respectively. The
      age-standardized rate was calculated and adjusted by the Chinese standard
      population in 1982 as well as the Segi's world standard population. RESULTS:
      There were 2803 new diagnosed oral cavity and pharyngeal cancer cases, 1793 male
      and 1010 female, with the sex ratio at 1.78: 1. The crude incidence rate of oral
      cavity and pharyngeal cancer was 3.28/100 000(2803/85 470 522). The crude
      incidence rate of males was 4.15/100 000(1793/43 231 554) while it was 2.39/100
      000(1010/42 238 968) among females. The age-standardized incidence rates by
      Chinese standard population (ASIRC) and the world standard population were
      1.72/100 000 and 2.23/100 000 respectively, and the cumulative rate and cut rate
      was separately 0.26% and 4.02/100 000. The crude incidence and ASIRC of oral
      cavity and pharyngeal cancers were 3.87/100 000 (2225/57 489 009) and 1.97/100
      000 in urban areas, whereas in rural areas, they were 2.07/100 000(578/27 981
      513) and 1.17/100 000. There were 1172 death cases, including 825 males and 347
      females. The crude mortality rate was 1.37/100 000 (1172/85 470 522), while it
      was 1.91/100 000(825/43 231 554) among males and 0.82/100 000(347/42 238 968)
      among females. The age-standardized incidence rates were 0.64/100 000 and
      0.88/100 000 respectively, by Chinese standard population (ASMRC) and the world
      standard population. The cumulative mortality rate (0-74 age years old) and cut
      rate were separately 0.10% and 1.34/100 000. The mortality and ASMRC were
      1.59/100 000(915/57 489 009) and 0.72/100 000 in urban areas, whereas in rural
      areas, they were 0.92/100 000(257/27 981 513) and 0.48/100 000 respectively.
      CONCLUSIONS: Both the incidence and mortality of oral cavity and pharyngeal
      cancer in China were still low in 2009.

PMID- 24304949
TI  - [Incidence and mortality of cancer in Zhejiang province in 2009].
AB  - OBJECTIVE: To investigate the incidence and mortality of cancer registered in
      Zhejiang province in 2009. METHODS: The statistics of incidence and mortality of
      cancer were collected from 6 population-based cancer registries in Zhejiang
      province, including 30 613 new incidence cases and 16 920 death cases reported in
      2009. The 6 cancer registries covered population at 9 560 699 in all. The crude
      rate, age-standardized rate, cumulative rate (0-74 years old), cut rate (35-64
      years old), age-specific rate of incidence/mortality as well as the constitution
      of top 10 common cancers were then calculated and analyzed. The age-standardized
      rate was calculated and adjusted by the Chinese standard population in 1982 as
      well as the Segi's world standard population. RESULTS: The crude incidence of
      cancer was 320.20/100 000. Age-standardized incidence by Chinese standard
      population and by world standard population were separately 161.99/100 000 and
      207.92/100 000, the cumulative rate was 23.83% and the cut rate was 346.87/100
      000. Meanwhile, the crude mortality rate was 176.97/100 000, and the age
      standardized mortality by Chinese standard population and by world standard
      population were 79.17/100 000, 107.02/100 000, respectively; and the cumulative
      mortality rate was 12.23% and cut rate was 139.75/100 000. Age-specific incidence
      among 0-34 years old population remained low; however, the incidence among 35-39
      age group increased obviously (116.46/100 000, 954 cases). The incidence among 45
      49 age group elevated even more sharply (272.97/100 000, 2388 cases) and finally
      reached the peak among 80-84 age group (1564.36/100 000, 2272 cases). Age
      specific mortality arose among 40-44 age group (48.06/100 000, 424 cases) and
      reached its peak among 80-84 age group (1392.23/100 000, 2022 cases) as well. The
      most common types of cancer were lung cancer, gastric cancer, colorectal cancer,
      liver cancer, breast cancer, esophageal cancer, thyroid cancer, pancreatic
      cancer, cervical cancer and lymphoma, which accounted for 74.37% (22 763/30 613)
      of all new cancer cases.Lung cancer, liver cancer, gastric cancer, colorectal
      cancer, esophageal cancer, pancreatic cancer, leukemia, lymphoma, brain tumors
      and breast cancer accounted for 87.75% (14 848/16 920) of all cancer deaths.
      CONCLUSION: The incidence and mortality of cancer both increased in 2009
      according to the statistics from cancer registry in Zhejiang province.Lung
      cancer, malignant tumor in digestive system and breast cancer were still the key
      challenges in cancer prevention and control. Meanwhile, the increased incidence
      of thyroid cancer should also be noticed.

PMID- 24304950
TI  - [Analysis of cancer incidence and mortality in Henan province, 2009].
AB  - OBJECTIVE: To analyze the cancer incidence and mortality of Henan province in
      2009. METHODS: On basis of the criteria of data quality from the National Central
      Cancer Registry (NCCR), data from 6 registries in Henan province were evaluated,
      covering 6 061 564 people, accounting for 6.45% of the total population in Henan
      in 2009. There were 3 104 991 people of males, and 2 956 573 people of females.
      The incidence, mortality, 10 most common cancers, constitution and cumulative
      rate (0-74 years old) were then calculated. The age-standardized rate was
      calculated and adjusted by the Chinese standard population in 1982 as well as the
      Segi's world standard population. RESULTS: There were 12 091 new diagnosed cancer
      and 8040 death cases registered in Henan province in 2009. The rate of
      pathological diagnosis was 68.2% (8246/12 901) and only 1.75% (2116/12 901) had
      death certificates. The ratio of mortality and incidence was 0.66 (8040/12 091).
      The incidence rate was 199.47/100 000 (12 091/6 061 564) in total, and it was
      216.36/100 000(6718/3 104 991) in males and 181.73/100 000(5373/2 956 573) among
      females. The standardized incidence by Chinese population was 126.50/100 000 and
      it was 166.08/100 000 by world's population. The cumulative rate was 19.95%
      between 0 and 74 years old. The incidence was the highest in Linzhou city, whose
      standardized incidence was 156.87/100 000 by Chinese population and the incidence
      was the lowest in Shenqiu city, whose standardized incidence was 104.82/100 000
      by Chinese population. The morphology verified cases accounted for 68.2% (8246/12
      091), death certification cases only accounted for 1.75% (2116/12 091), and
      mortality to incidence ratio was 0.66 (8040/12 091). The crude incidence in
      cancer registration areas of Henan province was 199.47/10 000 (12 091/6 061 564),
      216.36/10 000(6718/3 104 991) for males, 181.73/10 000 (5373/2 956 573) for
      females, age-standardized incidence rates by Chinese standard population and by
      world standard population were 126.50/10 000 and 166.08/10 000 with cumulative
      incidence rate (0-74 age years old) of 19.95%. The crude mortality in cancer
      registration areas of Henan province was 132.64/100 000 (8040/6 061 564),
      separately 160.58/100 000 (4986/3 104 991) for males and 103.30/10 000 (3054/2
      956 573) for females. The age-standardized mortality rates by Chinese standard
      population and by world's standard population were 78.41/10 000 and 107.49/10
      000. The cumulative mortality rate (0-74 age years old) was 12.18%. The mortality
      rate was the highest in Linzhou city, whose standardized rate was 93.35/100 000
      by Chinese population, and the lowest mortality rate was in Yuzhou city, whose
      standardized rate was 67.95/100 000. The most common cancers were lung cancer,
      esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer,
      brain nervous system cancer, colon cancer, cervical cancer and uterus cancer, all
      of which accounted for 82.23% (9943/12 091) of the registered cancers.Lung
      cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum
      cancer, brain nervous system cancer, pancreas cancer, colon cancer and
      gallbladder carcinoma were the major causes for the death, accounting for 86.30%
      (6938/8040) of all cancer deaths. CONCLUSION: Both incidence and mortality of
      cancer in Henan province were lower than the level in China, prevention and
      control should be implemented based on practical situation.

PMID- 24304951
TI  - [The association between body mass index, waist circumference with body fat
      percent, and abdominal fat rate in overweight and obese pupils].
AB  - OBJECTIVE: To study the association between body mass index(BMI), waist
      circumference (WC) with body fat percent, and abdominal fat rate in overweight
      and obese pupils. METHODS: Using convenience sampling, two primary schools of
      Dongcheng district in Beijing were selected in May 2010. A total of 162
      overweight and obese pupils graded from 2 to 5 who met the criteria of overweight
      and obese were recruited based on the physical exam record of the school medical
      department in April. Their physical measurements were taken to measure body fat
      percent (PBF), abdominal fat rate and visceral fat level and BMI was
      calculated.Independent-sample t test and Wilcoxon rank sum test were applied to
      analyze the gender differences. Correlation analysis was used to explore the
      association between the indexes of fat distribution (PBF, abdominal fat rate and
      visceral fat level) and BMI and WC.Univariate regression analysis was conducted
      to determine the variance of three indexes of fat distribution explained by the
      independent variables. RESULTS: The PBF of overweight and obese pupils was (43.62
      +/- 2.98) %, the abdominal fat rate of them was (28.06 +/- 6.02)%, the visceral
      fat level of them was 7.51 +/- 3.43, BMI was (23.41 +/- 2.83) kg/m(2). WC, PBF
      and abdominal fat rate were (78.57 +/- 7.76) cm, (42.36 +/- 2.56) % and (26.47 +/
      5.39) % in boys and (73.34 +/- 7.22) cm, (45.88 +/- 2.26) %, (30.92 +/- 6.07) %
      in girls. The difference in gender was significant (t values were -4.218, 8.751,
      4.811, respectively, all P values <0.01). The visceral fat level of boys and
      girls were 8.86 +/- 3.42 and 5.09 +/- 1.70, with significant difference (Z = 
      7.08, P < 0.01). The correlation between PBF and BMI and the variance of PBF
      explained by BMI (r = 0.563, R(2) = 31.7%) were stronger than them with WC (r =
      0.402, R(2) = 16.1%) (P < 0.01). The correlation between visceral fat levels and
      WC and the variance of visceral fat level explained by WC (r = 0.723, R(2) =
      57.3%) were higher than them with BMI (r = 0.621, R(2) = 41.7%) (P < 0.01).
      CONCLUSION: The correlation and prediction ability of BMI and body fat percent
      were stronger than WC, while the correlation and prediction ability of WC and
      visceral fat were higher than BMI.

PMID- 24304952
TI  - [Association between the distribution of feeding index and physical development
      of infants and young children aged 6-35 months in rural areas of Lhasa in 2010].
AB  - OBJECTIVE: Using infant and child feeding index (ICFI) to evaluate the
      relationship between infant feeding and physical development indicators in rural
      areas of Lhasa. METHODS: In July and August 2010 in the rural areas of Lhasa, the
      multi-stage cluster random sampling method was adopted to select 540 Tibetan
      children who were between 6 to 35 months of age. There were 70, 79 and 391 cases
      in 6 to 8, 9 to 11 and 12 to 35-month-old group respectively. The basic status of
      infants, information about breastfeeding and complementary feeding were collected
      by using designed questionnaires. Their height and weight were measured to
      calculate the children's weight for age Z-score (WAZ), height for age Z-score
      (HAZ) and weight for height Z-score (WHZ) and assess feeding index score (out of
      17 scores) and analyze the relationship between feeding index and HAZ, WAZ and
      WHZ. RESULTS: The mean ICFI score of 540 cases was 8.90 +/- 2.82.It was 6.84 +/-
      3.16, 8.16 +/- 2.78 and 9.41 +/- 2.55 for 6 to 8, 9 to 11 and 12 to 35-month-old
      infants respectively. There was significant difference between the different
      month group (F = 30.99, P < 0.05).For the three month groups, the scores of WAZ
      were 0.10 +/- 1.18, -0.09 +/- 1.20 and -0.38 +/- 0.96; HAZ were -0.60 +/- 1.68, 
      1.02 +/- 1.72 and -1.30 +/- 1.30; WHZ were 0.62 +/- 1.23, 0.69 +/- 0.96 and 0.43
      +/- 0.95 respectively. The ICFI scores of 9 to 11, 12 to 35 and 6 to 35-month-old
      infants were positively correlated with HAZ (correlation coefficients were
      0.25,0.12 and 0.09 respectively, all P values <0.05). There was no correlation
      with WAZ (correlation coefficients were 0.15,0.08 and 0.03 respectively, all P
      values >0.05) and WHZ (correlation coefficients were -0.08, -0.02, and -0.07
      respectively, all P values >0.05). There were no correlation between ICFI score
      with HAZ, WAZ and WHZ for 6 to 8 month-old infants (correlation coefficient were
      0.06,0.16 and -0.07 respectively, all P values >0.05). CONCLUSION: To some
      extent, the feeding index can effectively reflect the growth status of these
      infants and can serve as a comprehensive assessment of feeding situations among
      Tibetan children in rural areas of Lhasa.

PMID- 24304953
TI  - [Investigation on distribution of Yersinia enterocolitica in Henan province
      between 2005 and 2011].
AB  - OBJECTIVE: To investigate the distribution of Yersinia enterocolitica in Henan
      province from 2005 to 2011. METHODS: A total of 6700 samples of stool specimen
      were collected from diarrhea patients and different domestic animals between 2005
      and 2011 from Zhengzhou, Suixian and Dengfeng, as well as flies and the daub
      specimens of raw and cooked meat products. The bacteria were isolated by cold
      enrichment method, analyzed by the systematic biochemistry to determine the
      serotypes and bio-types, and tested the virulence genes by PCR method. RESULTS: A
      total of 216 strains of Yersinia enterocolitica were isolated from 11 kinds of
      animal hosts and foods, while 29.63% (64/216) of them were from swine. The
      dominant epidemic serotypes of the Yersinia enterocolitica were O: 5 and O: 8,
      accounted for 23.2% (50/216) and 20.4% (44/216), respectively; type 1A was the
      dominant bio-type, accounted for 84.7% (183/216). The dominant serotype and bio
      type differed a lot among various hosts.16 pathogenic strains were isolated from
      swine, followed by diarrhea patients (6 strains) and dogs (6 strains).
      CONCLUSION: The distribution of the host of Yersinia enterocolitica was
      widespread, while swine was the dominant animal host.

PMID- 24304954
TI  - [Variations on hemagglutinin gene of Zhejiang measles virus strains and
      differences with measles strains circulated both at home and abroad].
AB  - OBJECTIVE: To investigate the variations on hemagglutinin (H) gene of measles
      virus (MV) in Zhejiang province, and to analyze the differences with strains
      circulated both at home and abroad. METHODS: In total, 33 MV strains isolated in
      Zhejiang province between 1999 and 2011 were collected.RNA of the isolated MV
      strains was extracted and the complete sequences on H gene were amplified using
      RT-PCR assay. The products were compared with the Chinese vaccine strain Shanghai
      191, which was downloaded from GenBank, and other 95 different MV strains from
      all over the world. RESULTS: 33 MV strains, isolated from the throat swab
      specimens collected from MV patients in Zhejiang province during 1999 to 2001,
      were used to conduct phylogenetic analysis with MV strains circulated in other
      areas of China during 1993 to 2007. The phylogenetic tree based on H gene
      sequences showed that all the Zhejiang MV strains located in H1a cluster, and no
      apparent time series and geographic restrictions were observed. Compared to the
      referenced vaccine strain Shanghai-191, the average variation rate on nucleotides
      and amino acids, and the evolutionary rate of H1a viruses from China during 2003
      to 2011 were separately 5.15%, 4.44% and 5.81%, which were higher than the rates
      of H1a viruses during 1965 to 1993 (4.75%, 3.86% and 5.30%), and the rates of
      viruses during 1994 to 2002 (4.80%, 4.08% and 5.37%).However, the dn/ds ratios of
      strains within the three time periods were 0.19,0.21 and 0.23 respectively, which
      indicated that no evidence of positive selection was found on H1a MV strains
      during 1993 to 2011. A 24 stable amino acid variation sites on H gene was found
      between H1a viruses during 2003 to 2011 and the vaccine strain Shanghai-191. The
      largest variation occurred between vaccine and H1a strains, with 0.053 of the p
      distance and 26-28 of amino acid mutations.However, only 15 stable amino acid
      variations were found between vaccine strain and genotype B3 or D4 strains.In
      addition, significant differences were found between H1a viruses and genotype B
      or D viruses, with 0.074 and 0.071 of p-distance and 27-33 of amino acid
      differences. CONCLUSION: Significant differences were found on H gene between MV
      strains subtype H1a and vaccine strains and other genotype strains. The
      variations were enlarged with the time coursing; therefore, the surveillance on
      variation of Chinese MV strains should be taken into account.

PMID- 24304955
TI  - [Impact of the waist circumference change on new onset of diabetes in the
      population with impaired fasting glucose].
AB  - OBJECTIVE: To explore the impact of the waist circumference change on new onset
      diabetes (NOD) in the impaired fasting glucose (IFG) population. METHODS: A total
      of 12 657 subjects who took part in the health examination from 2006 to 2007 and
      from 2010 to 2011 from the employees of Kailuan Group and met the inclusion
      criteria were selected as the observation cohort.Of the 12 657 subjects, 10 697
      were male, 1960 were female, with age of (49.9 +/- 11.3) years old. According to
      the baseline waist circumference (WC) measurements and its quartile in the health
      examinations during 2006 to 2007, the observation population was divided into
      four groups (first, second, third and the fourth quartile groups) . Multiple
      logistic regression analysis was used to test the relation between the increasing
      of WC and NOD. RESULTS: The incidences in the IFG population of NOD were 4.27%
      (1884/12 657) in the total population;4.25% (1581/10 697) in male and 4.44%
      (303/1960) in females, respectively (P < 0.05) . Along with increasing WC in the
      4 quartile groups, the incidences of NOD was progressively increased, which were
      2.19% (235/3083) , 3.07% (333/3114) , 4.47% (473/3037) and 7.08% (843/3423) ,
      respectively;2.34% (213/2626) , 3.06% (282/2645) , 4.37% (393/2582), 7.00%
      (693/2844) in males and 1.38% (22/457) , 3.12% (51/469) , 5.05% (80/455) , 7.45%
      (150/579) in female (P < 0.05) . Multiple logistic regression analysis showed
      that compared with the first quartile group, the second, third and fourth
      quartile group had increased risk of NOD after adjusting for age, gender and
      other risk factors, the OR (95%CI) values were 1.38(1.13-1.68), 1.79 (1.47-2.09)
      and 3.10 (2.57-3.75), respectively. CONCLUSION: The incidence of NOD in the IFG
      population increased as the WC increased.

PMID- 24304956
TI  - [Study on the functions of potential new genes of Yersinia pestis type three
      secretion system].
AB  - OBJECTIVE: To investigate the functional relations between the putative proteins
      YpCD1.08, YpCD1.09, YpCD1.16 encoded in pCD1 plasmid of Yersinia pestis and its
      type III secretion system (T3SS). METHODS: Mutants of YpCD1.08, YpCD1.09,
      YpCD1.16 were constructed using lambda-Red recombinant system. The growth curves
      of the mutant strains cultivated in TMH medium with or without calcium at 26 
      degrees C and 37  degrees C were determined to analyze the low calcium response
      phenotype. The transcription levels of DeltaYpCD1.08, DeltaYpCD1.09,
      DeltaYpCD1.16 in Yersinia pestis and the dependence to temperature were
      determined using real time RT-PCR after cultivation at 26  degrees C and 37 
      degrees C and extraction of RNA. A beta-lactamases reporter system was adopted to
      study the influence of these genes on the translocation of effector YopE of T3SS.
      RESULTS: When grown in TMH medium without calcium at 26  degrees C and 37 
      degrees C, the growth curve of the YpCD1.08, YpCD1.09, YpCD1.16 mutants were
      similar to that of the wild-type strain, indicating that the low calcium response
      of all the mutants were normal. The ratios of YpCD1.08, YpCD1.09, YpCD1.16 gene
      transcriptional level at 37  degrees C and 26  degrees C were 2.3 +/- 0.3, 2.3 +/
      0.5 and 3.2 +/- 0.7, respectively, indicating that these genes were transcribed
      in Yersinia pestis and their transcription regulations showed a temperature
      dependence that was consistent with the well established temperature-dependent
      expression of Yersinia T3SS genes. The beta-lactamases reporter assays
      demonstrated that DeltaYpCD1.08 could translocate much higher level of YopE into
      HeLa cells, since that the light intensity ratio of 477/520 nm at 140 min was
      2.5, whereas it was 1.8 for the wild-type strain, and the values in DeltaYpCD1.09
      and DeltaYpCD1.16 were similar to the wild-type strain. CONCLUSION: YpCD1.08,
      YpCD1.09, YpCD1.16 gene are likely to be the new members of T3SS, and the
      putative protein YpCD1.08 could play some roles in YopE secretion and
      translocation.

PMID- 24304957
TI  - [Expression and bioinformatic analysis of miR-29 family, target gene IFN-gamma in
      CD4(+) T cells from subjects with latent tuberculosis infection].
AB  - OBJECTIVE: To investigate the effect of latent and active pulmonary
      tuberculosis(TB) on expression of miR-29 family and target gene IFN-gamma in
      CD4(+)T cells. METHODS: Subjects from two hospitals of Weifang were enrolled from
      March 2012 to December 2012 and divided into three groups: active TB group(30
      cases), latent tuberculosis infection(LTBI) group(25 cases) and healthy control
      group(30 cases). CD4(+) T cells in blood were collected from the three
      groups.Levels of miR-29a, miR-29b and miR-29c were measured by nucleic acid
      hybridization and RT-qPCR.Expression of IFN-gamma was analyzed by RT-qPCR. Target
      genes of miR-29 family were predicted with both TargetScan and PicTar.GO
      annotation and pathway overrepresentation were further analyzed with David
      database and Cytoscape. RESULTS: Levels of miR-29a, miR-29b and miR-29c showed
      significant differences among the three groups(P < 0.05): levels of miR-29b and
      miR-29c in the active TB group(561.63 +/- 65.36, 281.85 +/- 42.78) were higher
      than the healthy controls(260.74 +/- 38.69, 128.21 +/- 19.98), but lower than the
      LTBI group(2030.29 +/- 321.68, 620.93 +/- 79.14); expression of miR-29a in the
      healthy control group(913.95 +/- 104.73) were higher than the active TB
      group(323.37 +/- 54.38), but lower than the LTBI group(4782.13 +/- 567.81).Level
      of IFN-gamma showed significant differences among the three groups(P < 0.05):
      level of IFN-gamma in the LTBI group(0.45 +/- 0.09) were lower than the healthy
      controls(1.00), but higher than the active TB group(0.11 +/- 0.03). The target
      genes of miR-29 family mainly existed in molecular function such as extracellular
      matrix structural constituent and transcription regulator activity.In KEGG
      pathway, the gene set mostly existed in signaling pathway such as Focal
      adhesion,ECM-receptor interaction and mTOR signaling pathway. CONCLUSION: The
      expression of miR-29 family was increased and target gene IFN-gamma in CD4(+) T
      cells was decreased by latent and active pulmonary TB, which might play important
      role in alteration of signal pathway.

PMID- 24304958
TI  - [Three quantitative methods to continuously monitor Legionella in spring water].
AB  - OBJECTIVE: To compare the detection effect of Legionella pollution in spring
      water by three methods, namely traditional plating method, fluorescent
      quantitation PCR method and ethidium monoazide (EMA) fluorescent quantitation PCR
      method. METHODS: Every month (except May), we collected 11 water samples from the
      5 selected hot spring pools in one hot spring resort in Beijing in 2011. A total
      of 121 water samples were collected, and then were detected by the above three
      methods qualitatively and quantitatively. RESULTS: In our study, the Legionella
      pollution rate was separately 74.4% (90/121), 100.0% (121/121) and 100.0%
      (121/121) by the above three methods. The quantitative value of Legionella in the
      121 water samples detected by the three methods were around 0.10-216.00 colony
      forming units (CFU)/ml, 1.47-1557.75 gene units (GU)/ml and 0.20-301.69 GU/ml,
      respectively. The median (25th and 75th percentiles) was 75.30 (32.51-192.10)
      GU/ml, 36.46 (16.08-91.21) GU/ml and 5.30 (0.00-33.70) CFU/ml, respectively. The
      difference in the quantitative value of Legionella detected by the three methods
      showed statistical significance (chi(2) = 187.900, P < 0.01). The quantitative
      value of Legionella detected by fluorescent quantitation PCR method was the
      highest, followed by the value Legionella detected by EMA-fluorescent
      quantitation PCR method and traditional plating method. CONCLUSION: The
      sensitivity of the PCR methods was higher than traditional plating method, in
      detecting Legionella pollution in spring water, especially the EMA- fluorescent
      quantitation PCR method, which was more suitable for detecting Legionella in
      water.

PMID- 24304959
TI  - [Simultaneous determination of melamine and cyanuric acid residues in water and
      urine by solid phase extraction-hydrophilic interaction liquid chromatography
      electrospray tandem mass spectrometry method].
AB  - OBJECTIVE: We aimed to establish a sensitive quantified method for the
      simultaneous determination of melamine and cyanuric acid residues in water and
      urine by hydrophilic interaction liquid chromatography coupled with electrospray
      tandem mass spectrometry (HILIC-ESI-MS/MS) with the pretreatment of hydrophilic
      functional silica gel and cation exchange resin mixed solid phase extraction
      column(MCT), and to investigate the melamine and cyanuric acid residues in 501
      water and 216 urine from several province and city. METHODS: About 100 ml water
      (or 10 ml urine) was adjusted to pH 3.0 with concentrated hydrochloric acid, and
      then mixed with the internal standard solution((15)N3-melamine and (15)N3-(13)C3 
      cyanuric acid) and 100 ml acetonitrile (10 ml for urine). The solution was
      cleaned with MCT solid-phase extraction column, and eluted once by 3 ml methanol
      and twice by 2.5 ml methanol (containing 5% ammonia water). The effluent was
      collected and dried by N2 flow at 40  degrees C, and then diluted to 2 mmol/L
      ammonium acetate containing 90% volume fraction acetonitrile. The completely
      dissolved solution was then filtered with 0.22 um organic membrane; and the
      filtrate was detected by high performance liquid chromatography-tandem mass
      spectrometry and quantified with internal standards. The repeatability and
      sensitivity of the assay were evaluated. Then we detected the melamine and
      cyanuric acid residues in 501 water and 216 urine samples collected from several
      province and city. RESULTS: By the quantification of internal standard (15)N3
      melamine and (15)N3-(13)C3-cyanuric acid, the melamine and cyanuric acid were
      linear in the range of 2.0-1000.0 ug/L with correlation coefficient of 0.9998 and
      0.9997. The detection limits of the method were separately 0.4 ng/L (melamine)
      and 0.3 ng/L (cyanuric acid) for water, and 4.0 ng/L (melamine) and 3.0 ng/L
      (cyanuric acid) for urine. The average recovery rate was around 95.3%-100.1% with
      the relative standard deviation (RSD) was <4.02%. Out of the 501 water samples,
      melamine was detected out in 19.9% (100/501) and cyanuric acid was detected out
      in 5.2% (26/501). The content was around 0.03-5.00 g/L. Melamine or cyanuric acid
      was detected out in 24.5% of the urine samples (53/216), with the content around
      0.01-1.00 g/L. CONCLUSION: The established method of solid phase extraction
      hydrophilic interaction liquid chromatography-electrospray tandem mass
      spectrometry can satisfy the requirement for detection of melamine and cyanuric
      acid residues in all sorts of water and urine. Meanwhile, the two substances
      widely existed in water and Chinese population.

PMID- 24304960
TI  - [The applicable study of two models used in the assessment of long-term exposure
      to food lead].
AB  - OBJECTIVE: To compare the results of observed individual means (OIM) model with
      beta binomial-normal (BBN) model and to apply the two models to assessment of
      long-term dietary lead exposure. METHODS: Food consumption data were obtained
      from the National Nutrition and Health Survey conducted in 2002 by 24-hour recall
      method. Contamination data were derived from the national food contamination
      monitoring program from 2000 to 2006 and from monitoring data of Customs exports
      for agricultural products between 2005 and 2006. By multiplying the average
      consumption of food with the average concentration of contaminant, the OIM model
      calculated dietary intake per day. By correcting the within-person variation and
      keeping the between-person variation, the BBN model built dietary intake in the
      long-term.Using the example of food lead data, the results of two models were
      compared. RESULTS: The high-end percentile of OIM model was higher than the BBN
      model in various age groups.In the general population, the dietary intake of OIM
      model from 25th percentile to 99.9th percentile was between 1.167 and 7.313
      ug*kg(-1)*d(-1), and the dietary intake of BBN model with the same percentile
      range was between 1.193 and 5.729 ug*kg(-1)*d(-1). The median of various groups
      was similar between the two models. The dietary intakes in the general population
      of two models were 1.543 and 1.579 ug*kg(-1)*d(-1). CONCLUSION: The high-end
      percentile of OIM model is more conservative than BBN model in the long-term
      dietary exposure assessment.

PMID- 24304961
TI  - A strong association between lipid accumulation product and diabetes mellitus in
      japanese women and men.
AB  - AIM: Lipid accumulation product (LAP) is a new continuous marker of lipid
      overaccumulation that predicts cardiovascular risk. The aim of this study was to
      determine the cutoff value for LAP and evaluate its usefulness. METHODS: Using a
      database of results of health checkup examinations for 10,170 Japanese workers
      (35-40 years of age) conducted at their workplaces, the cutoff value for a high
      LAP was calculated by analyzing receiver-operating characteristic (ROC) curves
      for the relationships of LAP with hyperglycemia and diabetes. RESULTS: The cutoff
      value for LAP was 21.1 for women and 37.2 for men. The values were similar when
      calculated by analyzing the ROC curves for the relationships with hyperglycemia
      and diabetes. Using these cutoff values, the prevalence of a high LAP was
      calculated to be 23.7% in women and 28.8% in men. The odds ratio for diabetes in
      the subjects with vs. those without a high LAP, calculated after adjusting for
      age, smoking, alcohol consumption and regular exercise, was 19.09 (95% CI: 6.57
      55.50) in women and 7.40 (95% CI: 5.10-10.75) in men. High odds ratios for
      hypertension (10.66 [95% CI: 7.77-14.63] in women and 7.31 [95% CI: 6.20-8.62] in
      men) were also obtained in the subjects with vs. those without a high LAP.
      CONCLUSIONS: Cutoff values for a high LAP in women and men were determined, and
      high odds ratios for diabetes and hypertension were obtained using the cutoff
      values for LAP. Further studies are needed to elucidate whether the proposed
      cutoff values are applicable to people of other ages, races and ethnicities.

PMID- 24304962
TI  - Validation of a venous thromboembolism risk assessment model in hospitalized
      chinese patients: a case-control study.
AB  - AIM: The appropriate selection of hospitalized patients for venous
      thromboembolism(VTE) prophylaxis is an important unresolved issue. We sought to
      validate the Caprini model, a famous individual VTE risk assessment model(RAM),
      in hospitalized Chinese patients. METHODS: We performed a retrospective case
      control study among unselected hospitalized patients admitted to a comprehensive
      hospital in China. A total of 347 patients were confirmed to have VTE during
      hospitalization, and 651 controls were randomly selected to match the patients
      according to medical service. Both the patients and controls were retrospectively
      assessed for the risk of VTE using the Caprini RAM. RESULTS: The average Caprini
      cumulative risk score in the patients was significantly higher than that observed
      in the controls(4.69+/-2.58 vs 3.16+/-1.82, p<0.0001). Compared with that
      observed in the low-risk group, a classification of high-risk according to the
      Caprini model was associated with a 1.65-fold increased risk of VTE(95%CI 1.05
      2.61), while that of highest-risk was associated with a 4.84-fold increased risk
      of VTE(95%CI 3.06-7.64). After further stratifying the highest risk level with a
      cumulative risk score of >=5 into scores of 5-6, 7-8 and >=9, the patients with a
      score of 5-6 were found to exhibit a 3.33-fold increased risk of VTE(95%CI 2.06
      5.40), those with a score 7-8 exhibited a 9.41-fold increased risk of VTE(95%CI
      4.90-18.08) and those with a score of >=9 exhibited a 24.69-fold(95%CI 7.98
      76.40) increased risk of VTE compared with their low-risk counterparts.
      CONCLUSIONS: Our study suggests that the Caprini RAM can be used to effectively
      stratify hospitalized Chinese patients into VTE risk categories based on
      individual risk factors. The classification of the highest risk level with a
      cumulative risk score of >=5 provided significantly more clinical information,
      and further stratification of this group of patients is needed.

PMID- 24304963
TI  - Prevalence of chronic pain, impact on daily life, and treatment practices in
      India.
AB  - OBJECTIVE: Chronic pain is of concern to health professionals, patients, society,
      and negatively impacts quality of life (QoL). The present epidemiologic study
      identified point prevalence of chronic pain in India, impact on individual's QoL,
      unveiling current pain treatment practices, and levels of satisfaction with
      treatment. METHODS: This epidemiological telephonic survey consisted of two
      questionnaires: screening questionnaire that assessed prevalence of pain, its
      frequency during the past week, intensity during last episode, sites of pain, and
      main causes, and in-depth questionnaire that evaluated demography, frequency,
      duration, and intensity of pain; impact of pain on QoL; respondent's perception
      regarding the attitude of their family, friends, and doctors toward their pain.
      RESULTS: A total of 5004 respondents were included from eight cities across
      India. The overall point prevalence of chronic pain was 13%, and the mean
      intensity of pain on NRS scale was 6.93. Respondents with chronic moderate and
      chronic severe pain were 37% and 63%, respectively. Pain in knees (32%), legs
      (28%), and joints (22%) was most prevalent. Respondents with chronic pain were no
      longer able to exercise, sleep, maintain relationships with friends and family,
      and maintain an independent lifestyle. About 32% of patients lost >=4 hours of
      work in the past 3 months. Majority (68%) of respondents were treated for pain
      with over the counter (OTC) drugs, and most were taking NSAIDs (95%). CONCLUSION:
      A significant population of India suffers from chronic pain, and their QoL is
      affected leading to disability. A proportion of respondents receiving pain
      treatment were taking nonprescription medications with a majority of respondents
      on NSAIDs. A very few were consulting pain management specialists.

PMID- 24304964
TI  - Comparison of intraoperative blood loss during spinal surgery using either
      remifentanil or fentanyl as an adjuvant to general anesthesia.
AB  - BACKGROUND: Remifentanil enhances intraoperative hemodynamic stability,
      suggesting that it may decrease intraoperative blood loss when included as an
      adjuvant to general anesthesia. This retrospective study compared intraoperative
      blood loss during spinal surgery in patients administered either remifentanil or
      fentanyl as an opioid adjuvant. METHODS: We reviewed clinical and surgical data
      from 64 consecutive laminoplasty or laminectomy patients treated at National
      Hospital Organization Zentsuji Hospital between April 2010 and March 2011.
      Patients received either remifentanil (n = 35) or fentanyl (n = 29) as an opioid
      analgesic during general anesthesia. In addition to intraoperative blood loss,
      indices of hemodynamic stability, including heart rate as well as systolic, mean,
      and diastolic blood pressure (BP), were compared over the entire perioperative
      period between remifentanil and fentanyl groups. RESULTS: The remifentanil group
      exhibited significantly lower intraoperative arterial BP than the fentanyl group.
      Intraoperative blood loss was also significantly lower in the remifentanil group
      (125 +/- 67 mL vs. 165 +/- 82 mL, P = 0.035). CONCLUSIONS: Intraoperative blood
      loss during spinal surgery was decreased in patients who received remifentanil as
      an opioid adjuvant, possibly because of lower intraoperative BP. A larger-scale
      prospective randomized controlled trial is warranted to confirm our results and
      to test whether remifentanil can decrease intraoperative blood loss during other
      surgical procedures.

PMID- 24304965
TI  - Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in
      Sjogren's syndrome as a proof of concept.
AB  - BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal
      cytokine for B-cell activation, is overexpressed by salivary gland (SG)
      epithelial cells in primary Sjogren's syndrome (pSS). DeltaBAFF, a physiological
      inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7 RNA was
      reengineered to deliver antisense sequences targeting BAFF splice regions. A
      major decrease of BAFF messenger RNA (mRNA) and protein secretion, concomitantly
      with the increase of DeltaBAFF mRNA, was observed in vitro. In vivo, SG retrograd
      instillation of nonobese diabetic mice by the modified U7 cloned into an adeno
      associated virus vector significantly decreased BAFF protein expression and
      lymphocytic infiltrates and improved salivary flow. This study offers a rationale
      for localized therapeutic BAFF inhibition in pSS and represents a proof of
      concept of the interest of exon skipping in autoimmune diseases. 

PMID- 24304966
TI  - Cooperative binding of Annexin A5 to phosphatidylserine on apoptotic cell
      membranes.
AB  - Healthy cells exhibit an asymmetric plasma membrane with phosphatidylserine (PS)
      located on the cytoplasmic leaflet of the plasma membrane bilayer. Annexin A5
      FITC, a PS binding protein, is commonly used to evaluate apoptosis in flow
      cytometry. PS exposed by apoptotic cells serves as a major 'eat-me' signal for
      phagocytes. Although exposition of PS has been observed after alternative
      stimuli, no clearance of viable, PS exposing cells has been detected. Thus,
      besides PS exposure, membranes of viable and apoptotic cells might exhibit
      specific characteristics. Here, we show that Annexin A5 binds in a cooperative
      manner to different types of dead cells. Shrunken apoptotic cells thereby showed
      the highest Hill coefficient values. Contrarily, parafomaldehyde fixation of
      apoptotic cells completely abrogates the cooperativity effect seen with dead and
      dying cells. We tend to speculate that the cooperative binding of Annexin A5 to
      the membranes of apoptotic cells reflects higher fluidity of the exposed
      membranes facilitating PS clustering. 

PMID- 24304967
TI  - Synchronisation and stability in river metapopulation networks.
AB  - Spatial structure in landscapes impacts population stability. Two linked
      components of stability have large consequences for persistence: first,
      statistical stability as the lack of temporal fluctuations; second,
      synchronisation as an aspect of dynamic stability, which erodes metapopulation
      rescue effects. Here, we determine the influence of river network structure on
      the stability of riverine metapopulations. We introduce an approach that converts
      river networks to metapopulation networks, and analytically show how fluctuation
      magnitude is influenced by interaction structure. We show that river
      metapopulation complexity (in terms of branching prevalence) has nonlinear
      dampening effects on population fluctuations, and can also buffer against
      synchronisation. We conclude by showing that river transects generally increase
      synchronisation, while the spatial scale of interaction has nonlinear effects on
      synchronised dynamics. Our results indicate that this dual stability - conferred
      by fluctuation and synchronisation dampening - emerges from interaction structure
      in rivers, and this may strongly influence the persistence of river
      metapopulations. 

PMID- 24304968
TI  - Thermal interface resistance: crossover from nanoscale to macroscale.
AB  - In a recent work Gotsmann and Lantz have observed that the thermal interface
      conductivity for a nano-sized nominal contact area is proportional to the normal
      contact pressure in a wide pressure range, with a prefactor which is typically
      ~10(3) higher than observed for the same materials at the macroscale. Here I
      discuss the cross-over from the nanoscale to the macroscale. I show that for
      macroscopic solids the spreading resistance will dominate the interfacial
      resistance in most cases.

PMID- 24304969
TI  - Invasion and transmission of Salmonella Kentucky in an adult dairy herd using
      approximate Bayesian computation.
AB  - BACKGROUND: An outbreak of Salmonella Kentucky followed by a high level of
      sustained endemic prevalence was recently observed in a US adult dairy herd
      enrolled in a longitudinal study involving intensive fecal sampling. To
      understand the invasion ability and transmission dynamics of Salmonella Kentucky
      in dairy cattle, accurate estimation of the key epidemiological parameters from
      longitudinal field data is necessary. The approximate Bayesian computation
      technique was applied for estimating the transmission rate (beta), the recovery
      rate (gamma) and shape (n) parameters of the gamma distribution for the
      infectious (shedding) period, and the basic reproduction ratio (R0), given a
      susceptible-infectious-recovered-susceptible (SIRS) compartment model with a
      gamma distribution for the infectious period. RESULTS: The results report that
      the mean transmission rate (beta) is 0.417 month-1 (median: 0.417, 95% credible
      interval [0.406, 0.429]), the average infectious period (gamma-1) is 7.95 months
      (median: 7.95, 95% credible interval [7.70, 8.22]), the mean shape parameter (n)
      of the gamma distribution for the infectious period is 242 (median: 182, 95%
      credible interval [16, 482]), and the mean basic reproduction ratio (R0) is 2.91
      (median: 2.91, 95% credible interval [2.83, 3.00]). CONCLUSIONS: This study shows
      that Salmonella Kentucky in this herd was of mild infectiousness and had a long
      infectious period, which together provide an explanation for the observed
      prevalence pattern after invasion. The transmission rate and the recovery rate
      parameters are inferred with better accuracy than the shape parameter, therefore
      these two parameters are more sensitive to the model and the observed data. The
      estimated shape parameter (n) has large variability with a minimal value greater
      than one, indicating that the infectious period of Salmonella Kentucky in dairy
      cattle does not follow the conventionally assumed exponential distribution.

PMID- 24304970
TI  - Managing the pain of labour: factors associated with the use of labour pain
      management for pregnant Australian women.
AB  - BACKGROUND: Despite high rates of women's use of intrapartum pain management
      techniques, little is known about the factors that influence such use. OBJECTIVE:
      Examine the determinants associated with women's use of labour pain management.
      DESIGN: Cross-sectional survey of a substudy of women from the 'young' cohort of
      the Australian Longitudinal Study of Women's Health (ALSWH). SETTING AND
      PARTICIPANTS: Women aged 31-35 years who identified as being pregnant or recently
      given birth in the 2009 ALSWH survey (n = 2445) were recruited for the substudy.
      The substudy survey was completed by 1835 women (RR = 79.2%). MAIN VARIABLES
      STUDIED: Determinants examined included pregnancy health and maternity care
      [including complementary and alternative medicine (CAM)] for their most recent
      pregnancy and any previous pregnancies. Participants' attitudes and beliefs
      related to both CAM and maternity care were also included in the analysis. MAIN
      OUTCOME MEASURES: The outcome measures examined were the use of both
      pharmacological and non-pharmacological pain management techniques (NPMT).
      RESULTS: Differences were seen in the effects of demographics, health service
      utilization, health status, use of CAM, and attitudes and beliefs upon use of
      intrapartum pain management techniques across all categories. The only variable
      that was identified as a determinant for use of all types of pain management
      techniques was a previous caesarean section (CS). DISCUSSION AND CONCLUSIONS: The
      effect of key determinants on women's use of pain management techniques differs
      significantly, and, other than CS, no one determinant is clearly influential in
      the use of all pain management options.

PMID- 24304971
TI  - Interaction of a Blumeria graminis f. sp. hordei effector candidate with a barley
      ARF-GAP suggests that host vesicle trafficking is a fungal pathogenicity target.
AB  - Filamentous phytopathogens, such as fungi and oomycetes, secrete effector
      proteins to establish successful interactions with their plant hosts. In contrast
      with oomycetes, little is known about effector functions in true fungi. We used a
      bioinformatics pipeline to identify Blumeria effector candidates (BECs) from the
      obligate biotrophic barley powdery mildew pathogen, Blumeria graminis f. sp.
      hordei (Bgh). BEC1-BEC5 are expressed at different time points during barley
      infection. BEC1, BEC2 and BEC4 have orthologues in the Arabidopsis thaliana
      infecting powdery mildew fungus Golovinomyces orontii. Arabidopsis lines stably
      expressing the G. orontii BEC2 orthologue, GoEC2, are more susceptible to
      infection with the non-adapted fungus Erysiphe pisi, suggesting that GoEC2
      contributes to powdery mildew virulence. For BEC3 and BEC4, we identified
      thiopurine methyltransferase, a ubiquitin-conjugating enzyme, and an ADP
      ribosylation factor-GTPase-activating protein (ARF-GAP) as potential host
      targets. Arabidopsis knockout lines of the respective HvARF-GAP orthologue
      (AtAGD5) allowed higher entry levels of E. pisi, but exhibited elevated
      resistance to the oomycete Hyaloperonospora arabidopsidis. We hypothesize that
      ARF-GAP proteins are conserved targets of powdery and downy mildew effectors, and
      we speculate that BEC4 might interfere with defence-associated host vesicle
      trafficking. 

PMID- 24304972
TI  - Genetic and epigenetic determinants mediate proneness of oncogene breakpoint
      sites for involvement in TCR translocations.
AB  - T-cell receptor (TCR) translocations are a genetic hallmark of T-cell acute
      lymphoblastic leukemia and lead to juxtaposition of oncogene and TCR loci.
      Oncogene loci become involved in translocations because they are accessible to
      the V(D)J recombination machinery. Such accessibility is predicted at cryptic
      recombination signal sequence (cRSS) sites ('Type 1') as well as other sites that
      are subject to DNA double-strand breaks (DSBs) ('Type 2') during early stages of
      thymocyte development. As chromatin accessibility markers have not been analyzed
      in the context of TCR-associated translocations, various genetic and epigenetic
      determinants of LMO2, TAL1 and TLX1 translocation breakpoint (BP) sites and BP
      cluster regions (BCRs) were examined in human thymocytes to establish DSB
      proneness and heterogeneity of BP site involvement in TCR translocations. Our
      data show that DSBs in BCRs are primarily induced in the presence of a genetic
      element of sequence vulnerability (cRSSs, transposable elements), whereas breaks
      at single BP sites lacking such elements are more likely induced by chance or
      perhaps because of patient-specific genetic vulnerability. Vulnerability to
      obtain DSBs is increased by features that determine chromatin organization, such
      as methylation status and nucleosome occupancy, although at different levels at
      different BP sites. 

PMID- 24304973
TI  - Follicular lymphoma-protective HLA class II variants correlate with increased HLA
      DQB1 protein expression.
AB  - Multiple follicular lymphoma (FL) susceptibility single-nucleotide polymorphisms
      in the human leukocyte antigen (HLA) class I and II regions have been identified,
      including rs6457327, rs3117222, rs2647012, rs10484561, rs9268853 and rs2621416.
      Here we validated previous expression quantitative trait loci results with real
      time reverse transcription quantitative PCR and investigated protein expression
      in B-lymphoblastoid cell lines and primary dendritic cells using flow cytometry,
      cell-based enzyme-linked immunosorbent assay and western blotting. We confirmed
      that FL-protective rs2647012-linked variants, in high linkage disequilibrium with
      the extended haplotype DRB1*15:01-DQA1*01:02-DQB1*06:02, correlate with increased
      HLA-DQB1 expression. This association remained significant at the protein level
      and was reproducible across different cell types. We also found that differences
      in HLA-DQB1 expression were not related to changes in activation markers or class
      II, major histocompatibility complex, transactivator expression, suggesting the
      role of an alternative regulatory mechanism. However, functional analysis using
      RegulomeDB did not reveal any relevant regulatory candidates. Future studies
      should focus on the clinical relevance of increased HLA-DQB1 protein expression
      facilitating tumor cell removal through increased immune surveillance. 

PMID- 24304974
TI  - Biting patterns and seasonality of Anopheles gambiae sensu lato and Anopheles
      funestus mosquitoes in Kamuli District, Uganda.
AB  - BACKGROUND: We investigated the biting patterns and seasonal abundances of
      Anopheles gambiae s.l. and An. funestus mosquitoes in Kamuli District, Uganda.
      METHODS: Hourly indoor and outdoor catches of human biting mosquitoes were
      sampled from 19.00 to 07.00 hours for four consecutive nights each month using
      bed net traps in forty-eight houses randomly selected from Bugabula county where
      insecticide-treated bed nets (ITNs) had been used for at least five years and
      Budiope county where ITNs had not been used. The indoor and outdoor human-biting
      fractions, time of biting of the anophelines and climatic data were recorded from
      January to December 2010. Data were analysed using Multi-way analysis of
      variance, Kruskal-wallis rank sum test and Pearson correlation. The number of
      mosquitoes caught biting humans and resting indoors, the indoor and outdoor human
      biting densities and biting rates during different hours of the night, and
      mosquito abundances for a twelve-month sampling period in both zones are
      reported. RESULTS: Approximately four times more Anopheles mosquitoes were caught
      biting humans in Budiope County than in the Bugabula zone, with An. gambiae s. l.
      catches exceeding those of An. funestus. In both zones, peak night biting
      occurred between 23.00 and 05.00 hours. The majority of bites occurred between
      03.00 and 06.00 hours for both Anopheles gambiae s. l. and funestus group.
      Outdoor biting densities of Anopheles gambiae s. l. exceeded the indoor biting
      densities throughout the night in both zones, while the indoor and outdoor human
      biting densities of An. funestus group were apparently equal. The outdoor and
      indoor human biting rates were similar in both zones. In Bugabula county, the
      abundance of An. gambiae s.l. was rainfall-dependent, while the An. funestus
      group could thrive with or without rain fall. In Budiope county, both An. gambiae
      s.l. and An. funestus mosquitoes thrived all year round regardless of the amount
      of rainfall. CONCLUSION: Considering the biting patterns, and seasonal abundances
      exhibited by Anopheles gambiae s.l. and An. funestus mosquitoes in Kamuli
      district, intensive use of ITNs combined with indoor residual spraying,
      environmental management and improved house designs in the context of integrated
      vector management may be the appropriate vector control strategy.

PMID- 24304975
TI  - Radiotherapy-related changes in serum proteome patterns of head and neck cancer
      patients; the effect of low and medium doses of radiation delivered to large
      volumes of normal tissue.
AB  - BACKGROUND: Conformal intensity-modulated radiation therapy (IMRT) involves
      irradiation of large volume of normal tissue with low and medium doses,
      biological relevance of which is not clear yet. Serum proteome features were used
      here to study the dose-volume effects in patients irradiated with IMRT due to
      head and neck cancer. METHODS: Blood samples were collected before and during RT,
      and also about one month and one year after the end of RT in a group of 72
      patients who received definitive treatment. Serum proteome profiles were analyzed
      using MALDI-ToF mass spectrometry in 800-14,000 Da range. RESULTS: Major changes
      in serum proteome profiles were observed between pre-treatment samples and
      samples collected one month after RT. Radiation-related changes in serum proteome
      features were affected by low-to-medium doses delivered to a large fraction of
      body mass. Proteome changes were associated with intensity of acute radiation
      toxicity, indicating collectively that RT-related features of serum proteome
      reflected general response of patient's organism to irradiation. However, short
      term dose-related changes in serum proteome features were not associated
      significantly with the long-term efficacy of the treatment. CONCLUSIONS: The
      effects of low and medium doses of radiation have been documented at the level of
      serum proteome, which is a reflection of the patient's whole body response.

PMID- 24304976
TI  - Risk determinants in early intervention use during the first postnatal year in
      children born very preterm.
AB  - BACKGROUND: Early interventions (EI) are recognised for their potential risk
      reduction capacity. Although developmental delay is common in children born very
      preterm reports continue to suggest poor uptake of EI services. This study
      examined the risk determinants of EI in Australian children born less than 32
      weeks gestation during the first year of life. METHODS: As part of a multi-centre
      randomised-trial, 195 children were prospectively studied during their first year
      of life and EI use, type of follow-up, perinatal, social and parental
      psychosocial risk factors were collected using questionnaires. Child
      neurodevelopmental disability-status was assessed at 12-months (cerebral palsy,
      blind, deaf, developmental quotient 1 standard deviation (SD) below mean). The
      associations between EI and variables were examined using Pearson's chi-squared
      test (chi2) and regression techniques. RESULTS: A total of 55% of children
      received EI, 51% attended post discharge neonatal intensive care unit (NICU) and
      the remainder attended exclusive primary health care. Risk factors included, 50%
      perinatal, 19% social and 34% psychosocial and at 12-months 23% were categorised
      as disabled. Low social risk and NICU follow-up attendance were significantly
      associated with EI use but only perinatal risk (OR 3.1, 95% CI 1.7, 5.6, p =
      <0.01) and disability (OR 2.2, 95% CI 1.1, 4.7, p = 0.04) independently predicted
      EI use. CONCLUSIONS: It is reassuring that children with perinatal risk receive
      EI, opportunity remains to improve EI uptake in families with social and parental
      psychosocial risk during the first year of life.

PMID- 24304977
TI  - Percutaneous posterior tibial nerve stimulation (PPTNS) in faecal incontinence
      associated with an anal sphincter lesion: results of a prospective study.
AB  - PURPOSE: Establish the efficacy of posterior tibial nerve stimulation in treating
      faecal incontinence associated to sphincter defect. METHODS: Prospective study
      that included patients with faecal incontinence associated to sphincter lesions
      between 90 and 180 degrees . Clinical anamnesis, physical examination, reverse
      visual analogic scale, incontinence diary and Wexner score were recorded at
      baseline and 6 months. Anal manometry was realized at baseline and 6 months.
      Subjects underwent one 30-min session every week for 12 consecutive weeks and was
      continued with 6 additional sessions every 2 weeks. RESULTS: Sixteen patients
      were analysed, 15 women and 1 men, with a mean age of 56.5 years. The
      incontinence were obstetric origin (50%) and perineal surgeries (50%). Four
      patients who did not continue with the second stage. Referring to the retention
      time, at baseline 12 patients (75%) did not bear even 1 min. At 6 months the
      retention time was <1 min in only 2 patients (p = 0.008). Median Wexner baseline
      values were 10; at 6 months decrease to 5 (p = 0.006). The visual analogical
      scale (VAS) increased from 6 to 7.5 (p > 0.05). After 6 months, maximum resting
      pressure increased from 40.9 to 51 mmHg (p < 0.001) and maximum squeeze pressure
      from 82.5 to 94 mmHg (p < 0.001). CONCLUSION: PTNS is an effective treatment for
      faecal incontinence associated to sphincter lesions because the number of
      incontinence episodes per week, the Wexner Score, the ability to defer
      defaecation and the manometric determinations improved significantly.

PMID- 24304978
TI  - PKPD Modeling of Predictors for Adverse Effects and Overall Survival in Sunitinib
      Treated Patients With GIST.
AB  - A modeling framework relating exposure, biomarkers (vascular endothelial growth
      factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR)-2, 
      3, soluble stem cell factor receptor (sKIT)), and tumor growth to overall
      survival (OS) was extended to include adverse effects (myelosuppression,
      hypertension, fatigue, and hand-foot syndrome (HFS)). Longitudinal
      pharmacokinetic-pharmacodynamic models of sunitinib were developed based on data
      from 303 patients with gastrointestinal stromal tumor. Myelosuppression was
      characterized by a semiphysiological model and hypertension with an indirect
      response model. Proportional odds models with a first-order Markov model
      described the incidence and severity of fatigue and HFS. Relative change in
      sVEGFR-3 was the most effective predictor of the occurrence and severity of
      myelosuppression, fatigue, and HFS. Hypertension was correlated best with
      sunitinib exposure. Baseline tumor size, time courses of neutropenia, and
      relative increase of diastolic blood pressure were identified as predictors of
      OS. The framework has potential to be used for early monitoring of adverse
      effects and clinical response, thereby facilitating dose individualization to
      maximize OS.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e85;
      doi:10.1038/psp.2013.62; advance online publication 4 December 2013. 

PMID- 24304979
TI  - The multiple roles of guanylate cyclase C, a heat stable enterotoxin receptor.
AB  - PURPOSE OF REVIEW: Guanylate cyclase C (GC-C) is a transmembrane receptor that is
      expressed primarily on intestinal epithelial cells. Activation of this receptor
      by its endogenous peptide ligands initiates cyclic guanosine monophosphate
      dependent (cGMP) salt and water movement in the intestine. GC-C is targeted by
      the enterotoxigenic Escherichia coli heat-stable enterotoxin STa, which
      deregulates this pathway and causes secretory diarrhea. This review discusses
      current work on the physiological function of GC-C in the intestine. RECENT
      FINDINGS: Familial GC-C mutations demonstrate that epithelial cGMP signaling is
      critical to electrolyte and fluid balance in the neonatal intestine. Chronic
      deregulation of GC-C activity in early life increases susceptibility to a number
      of disorders, including obstruction and inflammatory bowel disease. Murine models
      indicate that GC-C regulates the composition of intestinal commensal microflora
      and that it suppresses bacterial infection and modulates colonic injury and
      inflammation. Therapeutic GC-C ligands are used to successfully treat
      constipation-predominant irritable bowel syndrome and recent studies show that
      extracellular cGMP is an important mechanism of reducing abdominal pain
      associated with this disorder. SUMMARY: Originally identified as a target of E.
      coli enterotoxin STa, GC-C is an important regulator of physiological salt and
      water homeostasis and may directly impact a wide range of intestinal disorders.

PMID- 24304980
TI  - Typhoid epidemiology, diagnostics and the human challenge model.
AB  - PURPOSE OF REVIEW: Infection caused by ingestion of human-restricted Salmonella
      enterica serovars Typhi and Paratyphi predominantly affects the most impoverished
      sections of society. In this review, we describe recent advances made in
      estimating the burden of illness and the important role improved diagnostic tests
      may have in controlling infection and report the development of a new human
      challenge model of typhoid infection. RECENT FINDINGS: Typhoid continues to be a
      major cause of morbidity, particularly in children and young adults in south east
      Asia, although accurate assessments are still hindered by the lack of reliable
      surveillance data. Recent reports of high rates of infection in Africa and the
      dominance of paratyphoid in several geographic areas are of particular concern.
      Diagnosis of enteric fever remains frustrated by the nonspecific clinical
      presentation of cases and the lack of test sensitivity. Methods to improve
      diagnostic accuracy are hindered by the incomplete understanding of
      immunobiological mechanisms of infection and lack of a suitable animal infection
      model. SUMMARY: Enteric fever is a major global problem, the burden of which has
      only partially been recognized. Control strategies utilizing cheap accurate
      diagnostics and effective vaccines are urgently required, and their development
      should be accelerated by the use of a human challenge model.

PMID- 24304982
TI  - The changing face of medical education: are we ready?

PMID- 24304983
TI  - Treatment of decompensated cirrhosis secondary to hepatitis C with antiviral
      therapy.
AB  - OBJECTIVE: To treat decompensated hepatitis C patient with interferon, ribavirin
      and amantidine to ascertain the sustained viral response. STUDY DESIGN:
      Descriptive study. PLACE AND DURATION OF STUDY: Shifa International Hospital,
      Islamabad, from January 2007 to January 2012. METHODOLOGY: HCV PCR patients with
      decompensated hepatitis C, who had developed a complication like ascites,
      encephalopathy or variceal bleeding were included in the study. Those with
      uncontrolled ascites or other complications were excluded. Treatment with
      standard interferon 3 miU subcutaneously three times a week along with ribavirin
      800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months.
      Patients were followed every month with CBC and ALT and HCV PCR was performed
      after 3 months to document early viral response. They had HCV PCR at the end of
      the treatment to document end of treatment response. All were further followed
      for another 6 months at monthly intervals and HCV PCR was performed at the end of
      this period to document sustained viral response. RESULTS: In all, 165 patients
      were treated. Treatment had to be discontinued in 42 (26%) patients. Out of
      these, 16 patients died. Thus, 123 completed treatment. Sustained viral response
      was documented in 58 out of the 123 (47%) patients. Hepatic encephalopathy,
      gastrointestinal bleeding, sepsis and development of ascites were the major
      complications during treatment. CONCLUSION: Forty seven percent of patients with
      decompensated hepatitis C cirrhosis were able to achieve sustained viral response
      after one year treatment with anti-viral therapy. However, complications
      developed during treatment and, therefore, frequent and close monitoring is
      necessary in these patients.

PMID- 24304984
TI  - Outcome of radiologically placed tunneled haemodialysis catheters.
AB  - OBJECTIVE: To study the outcome of radiologically placed double lumen tunneled
      haemodialysis catheters for the management of renal failure. STUDY DESIGN: Case
      series. PLACE AND DURATION OF STUDY: Interventional Suite of Radiology Department
      at the Aga Khan University Hospital, Karachi, from April 2010 to June 2011.
      METHODOLOGY: All consecutive patients who were referred to the department of
      radiology by the nephrologists for double lumen tunneled haemodialysis catheter
      (Permacath) placement during the study period were included. Patients with
      septicemia, those for whom follow-up was not available, those coming for catheter
      exchange or who died due to a noncatheter related condition were excluded. A
      radio-opaque, soft silicone double lumen catheter was inserted through a
      subcutaneous tunnel created over the anterior chest wall. The catheter tip was
      placed in the right atrium via the internal jugular vein. Ultrasound guidance was
      used for initial venous puncture. The rest of the procedure was carried out under
      fluoroscopic guidance. Technical success, catheter related bacteremia rates,
      adequacy of dialysis, patency, and adverse events were analyzed. RESULTS: Overall
      88 tunneled haemodialysis catheters were placed in 87 patients. Patients were
      followed-up for duration of 1 - 307 days with mean follow-up period of 4 months.
      Immediate technical success was 100%. The procedural complication rate was 5.6%
      (5 catheters). Eight patients died during the study period, seven from causes
      unrelated to the procedure. One patient died due to septicemia secondary to
      catheter related infection. Of the remaining 69 patients, 50 (72.4%)
      predominantly had uneventful course during the study period. Twelve patients
      developed infection (17.3%); two were successfully treated conservatively while
      in 10 patients catheter had to be removed. Seven catheters (10.1%) failed due to
      mechanical problems. In 3 patients the internal jugular veins got partially
      thrombosed. One catheter was accidentally damaged in the ward and had to be
      removed. CONCLUSION: Radiological guided tunneled haemodialysis catheter
      placements are a safe and reasonable means of providing temporary vascular access
      for haemodialysis patients.

PMID- 24304985
TI  - Clinically significant contrast induced acute kidney injury after non-emergent
      cardiac catheterization--risk factors and impact on length of hospital stay.
AB  - OBJECTIVE: To evaluate the frequency and risk factors associated with clinically
      significant contrast-induced nephropathy (CIN) in patients undergoing non
      emergent coronary angiography. STUDY DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 2005
      to December 2007. METHODOLOGY: Case records of patients who underwent coronary
      angiography with a serum creatinine of 1.5 mg/dl at the time of procedure were
      evaluated. Clinically significant contrast induced nephropathy (CSCIN) was
      defined as either doubling of serum creatinine from baseline value within a week
      following the procedure or need for emergency hemodialysis after the procedure.
      RESULTS: One hundred and sixteen patients met the inclusion criteria. Mean age
      was 64.0 +/- 11.5 years, 72% were males. Overall prevalence of CIN was 17% (rise
      of serum creatinine by >= 0.5 mg/dl) while that of clinically significant CIN
      (CSCIN) was 9.5% (11 patients). Patients with CSCIN had significantly lower left
      ventricular ejection fraction (p = 0.03, OR: 0.24; 95% CI = 0.06 - 0.91) and
      higher prevalence of cerebrovascular disease (p < 0.001, OR: 14.66; 95% CI = 3.30
      - 65.08). Mean baseline serum creatinine was significantly higher, 3.0 +/- 1.5
      vs. 2.0 +/- 1.1 mg/dl (p = 0.03, OR: 1.47; 95% CI = 1.03 - 2.11) whereas mean GFR
      estimated by Cockcroft-Gault formula was significantly lower at 25 +/- 7.4 vs.
      41.0 +/- 14.6 ml/minute (p = 0.001, OR = 0.89, 95% CI = 0.84 - 0.95) at the time
      of procedure in patients with CSCIN. Mean length of hospital stay was
      significantly higher in this group compared to those without CIN, 9.0 +/- 5.1 vs.
      3.0 +/- 3.2 days (p = 0.001, OR = 1.31, 95% CI = 1.12 - 1.54). Multivariate
      analysis revealed low GFR (p = 0.001, OR = 0.88; 95% CI = 0.82 - 0.95) and low
      ejection fraction (p = 0.03, OR = 0.20; 95% CI = 0.04 - 0.91) to be independent
      factors associated with CSCIN. No significant differences were noted between the
      two groups in patients with hypertension, diabetes and heart failure. CONCLUSION:
      CSCIN is a significant concern in high risk groups despite prophylaxis. Patients
      with lower EF, cerebrovascular disease and low GFR at the time of procedure are
      more likely to have CIN.

PMID- 24304986
TI  - Pathogens causing blood stream infections and their drug susceptibility profile
      in immunocompromised patients.
AB  - OBJECTIVE: To determine the types of pathogens causing blood stream infections
      and their drug susceptibility profile in immunocompromised patients. STUDY
      DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY:
      Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from
      January to September 2012. METHODOLOGY: Blood culture bottles received from
      immunocompromised patients were dealt by two methods, brain heart infusion (BHI)
      broth based manual method and automated BACTEC system. The samples yielding
      positive growth from either of two methods were further analyzed. The
      identification of isolates was done with the help of biochemical reactions and
      rapid tests. Antimicrobial susceptibility of the isolates was carried out as per
      recommendations of Clinical and Laboratory Standards Institute (CLSI). RESULTS:
      Out of the 938 blood culture specimens received from immunocompromised patients,
      188 (20%) yielded positive growth. Out of these, 89 (47.3%) isolates were Gram
      positive and Gram negative each, while 10 (5.3%) isolates were fungi (Candida
      spp.). In case of Gram positive isolates, 75 (84.3%) were Staphylococcus spp. and
      51 (67%) were Methicillin resistant. Amongst Gram negative group 49 (55.1%)
      isolates were of enterobacteriaceae family, while 40 (44.9%) were non-lactose
      fermenters (NLF). In vitro antimicrobial susceptibility of Staphylococci revealed
      100% susceptibility to vancomycin and linezolid. The enterobacteriaceae isolates
      had better susceptibility against amikacin 85.7% compared to tigecycline 61.2%
      and imipenem 59.2%. For NLF, the in vitro efficacy of aminoglycosides was 72.5%.
      CONCLUSION: The frequency of Gram positive and Gram negative organisms causing
      blood stream infections in immunocompromised patients was equal. Vancomycin in
      case of Gram positive and amikacin for Gram negative organisms revealed better in
      vitro efficacy as compared to other antibiotics.

PMID- 24304987
TI  - Unilateral approach for bilateral decompression of lumbar spinal stenosis: a
      minimal invasive surgery.
AB  - OBJECTIVE: To assess the feasibility and efficacy of a novel, minimally invasive
      spinal surgery technique for the correction of lumbar spinal stenosis involving
      unilateral approach for bilateral decompression. STUDY DESIGN: Cross-sectional
      observational study. PLACE AND DURATION OF STUDY: Neurosurgery Department of
      PGMI, Lady Reading Hospital, Peshawar, from January to December 2010.
      METHODOLOGY: A total of 60 patients with lumbar stenosis were randomly assigned
      to undergo either a conventional laminectomy (30 patients, Group A), or a
      unilateral approach (30 patients, Group B). Clinical outcomes was measured using
      the scale of Finneson and Cooper. All the data was collected by using a proforma
      and different parameters were assessed for a minimum follow-up period of three
      months. Data was analyzed by descriptive statistics using SPSS software version
      17. RESULTS: Adequate decompression was achieved in all patients. Compared with
      patients in the conventional laminectomy group, patients who received the novel
      procedure (unilateral approach) had a reduced mean duration of hospital stay, a
      faster recovery rate and majority of the patients (88.33%) had an excellent to
      fair operative result according to the Finneson and Cooper scale. Five major
      complications occurred in all patient groups, 2 patients had unintended dural
      rent and 2 wound dehiscence each and fifth patient had worsening of symptoms.
      There was no mortality in the series. CONCLUSION: The ultimate goal of the
      unilateral approach to treat lumbar spinal stenosis is to achieve adequate
      decompression of the neural elements. An additional benefit of a minimally
      invasive approach is adequate preservation of vertebral stability, as it requires
      only minimal muscle trauma, preservation of supraspinous/intraspinous ligament
      complex and spinous process, therefore, allows early mobilization. This also
      shortens the hospital stay, reduces postoperative back pain, and leads to
      satisfactory outcome.

PMID- 24304988
TI  - Outcome of open transcortical approach in the management of intraventricular
      lesions.
AB  - OBJECTIVE: To evaluate the outcome of management of intraventricular lesions
      operated by an open transcortical (nonendoscopic) approach. STUDY DESIGN: Case
      series. PLACE AND DURATION OF STUDY: Department of Neurosurgery, Dow University
      of Health Sciences and Civil Hospital, Karachi, from January 2009 to December
      2011, with six months follow-up. METHODOLOGY: All cases with lesions in the
      lateral ventricle and anterior third ventricle operated by open transcortical
      approach, were included after informed consent. Total excision of the lesion was
      attempted in all cases. Patients were analyzed for outcome in terms of
      establishment of diagnosis, completeness of resection, morbidity and mortality.
      RESULTS: A total of 33 patients were operated. Twenty three were males and 10
      were females. Colloid cyst was diagnosed in 14 patients (42%), giant cell
      astrocytoma and choroid plexus papilloma in 4 cases each and subependymoma and
      central neurocytoma in 2 cases each, epidermoid, choroid plexus carcinoma,
      oligodendroglioma, metastasis, meningioma, ependymoma and cavernous hemangioma in
      one patient each. The overall outcome could be labeled as good in 24 out of 33
      cases (73%) and in 8 cases (24%) it was fair. One patient died due to
      ventriculitis and was categorized as poor outcome (3%). Postoperative
      complications included meningitis, seizures, intraventicular haemorrhage,
      subdural collection and transient hemiparesis. Nine patients had persistent
      hydrocephalus requiring ventriculoperitoneal shunt. CONCLUSION: Conventional open
      transcortical approach is still effective in getting conclusive biopsy or near
      total excision of the lesion with minimum morbidity.

PMID- 24304989
TI  - Vitamin D levels among pregnant and lactating women.
AB  - OBJECTIVE: To assess the serum level of vitamin D in pregnant and lactating
      women. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY:
      Gynaecological Unit 1 of Jinnah Hospital, Lahore, from December 2010 to May 2011.
      METHODOLOGY: A total of 100 women comprised of three groups: pregnant (n = 40),
      lactating (n = 40) and control (n = 20) groups. The information regarding age,
      educational level, socioeconomic status, exposure to sunlight and dietary vitamin
      D intake were collected through self-structured questionnaire. Serum
      concentration of vitamin D was measured by ELISA and serum calcium and phosphate
      levels were measured by chemistry analyzer. Statistical analysis was done using
      SPSS (version 13). The values were considered significant at 0.05 level of
      significance. RESULTS: The mean serum vitamin D level in the pregnant and
      lactating mothers was 26.5 +/- 17.1 nmol/L and 21.4 +/- 16.3 nmol/L respectively
      and in control group was 33.8 +/- 21.1 nmol/L. The mean calcium level in the
      pregnant, lactating and control group was 10.3 +/- 1.2 mg/dL, 9.7 +/- 1.3 mg/dL
      and 9.7 +/- 1.3 mg/dL respectively. The mean phosphate in pregnant was 3.2 +/-
      0.76 mg/dl, in lactating was 3.3 +/- 0.76 mg/dl and in control was 3.5 +/- 0.92
      mg/dl. Significant difference (p = 0.041 and p = 0.037 respectively) in the serum
      levels of vitamin D and calcium was observed among the pregnant and lactating
      women as compared to control group. CONCLUSION: Low serum vitamin D concentration
      was observed in lactating women and pregnant women as compared to control group.

PMID- 24304990
TI  - Efficacy of metformin versus insulin in the management of pregnancy with
      diabetes.
AB  - OBJECTIVE: To compare the efficacy of metformin with insulin in the management of
      pregnancy with diabetes. STUDY DESIGN: Randomized clinical trial. PLACE AND
      DURATION OF STUDY: Department of Obstetrics and Gynaecology, Maternal and Child
      Health Centre (MCH), Pakistan Institute of Medical Sciences, Islamabad, from May
      2010 to January 2011. METHODOLOGY: A total of 68 pregnant patients with diabetes
      were included in this study. Patients were randomly divided in to two groups of
      each 34 patients based on table of random numbers. One was labelled as group-A
      and other was labelled as group-B. Group-A received insulin and group-B received
      metformin for the management of diabetes. RESULTS: The mean age was 29.82 +/-
      4.58 and 29.35 +/- 4.97 years in groups-A and B respectively. Fasting blood sugar
      level after 1 month was controlled in 22 (64.7%) patients in group-A and in 27
      (79.4%) in group-B (p > 0.05). Fasting blood sugar level at term, remained
      controlled in 30 (88.2%) patients in group-A and 27 (79.4%) in group-B (p >
      0.05). Comparison of random blood sugar levels within normal limits after 1 month
      in 25 (73.5%) in group-A and in 24 (70.6%) in group-B. At term, random blood
      sugar level was controlled in 28 (82.4%) and 27 (79.4%) patients in group-A and
      B, respectively. Comparison of post-treatment HBA1C level depicts that diabetes
      controlled in 27 (79.4%) patients in group-A while in 28 (82.3%) patients of
      group-B. The efficacy of metformin and insulin in controlling diabetes was equal
      in two groups. CONCLUSION: There was no marked difference in efficacy of
      metformin and insulin in controlling diabetes in pregnant patients in two groups.

PMID- 24304991
TI  - Delayed sleep phase syndrome: a forerunner of psychiatric distress.
AB  - OBJECTIVE: To determine the association of extrinsic delayed sleep phase syndrome
      (DSPS) and psychiatric distress. STUDY DESIGN: Cross-sectional, analytical study.
      PLACE AND DURATION OF STUDY: Dow University of Health Sciences, Karachi, from
      July 2009 to September 2010. METHODOLOGY: Sales personnel employed in different
      shopping malls in Karachi operating from 2 pm afternoon to 12.00 mid-night were
      inducted. The instrument used to define DSPS included difficulty in falling sleep
      timely at night and early rising in the morning. The proven DSPS subjects were
      studied by the Aga Khan University Anxiety Depression Scale (AKUADS) to explore
      the association of extrinsic (motivational) DSPS with anxiety and depression
      syndrome along with a survey questionnaire having twelve questions based on the
      criteria of ICSD (International Classification of Sleep Disorder) on DSPS, to
      study different characteristics of these subjects and its relationship with
      psychiatric illness. RESULTS: Eight hundred and eleven subjects were inducted,
      majority were male (n = 757, 93.3%). Three hundred and forty-five (42.5%)
      subjects scored > 19 with mean value of 41.4 +/- 15.90. Result supported an
      association between DSPS and psychiatric distress. CONCLUSION: Extrinsic DSPS
      prevention necessitates attention because of its positive relationship with
      psychiatric distress.

PMID- 24304992
TI  - Population genetics and drug resistance markers: an essential for malaria
      surveillance in Pakistan.
AB  - Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of
      malaria cases in Pakistan. However, baseline epidemiological data on P. vivax
      population structure and drug resistance are lacking from Pakistan. For
      population structure studies, molecular genetic markers, circumsporozoite protein
      (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play
      an important role in P. vivax survival under immune and environmental pressure.
      Furthermore, these genes have also been identified as suitable candidates for
      vaccine development. While efforts for effective vaccine are underway, anti
      malarial agents remain the mainstay for control. Evidence of resistance against
      commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP)
      is threatening to make this form of control defunct. Therefore, studies on drug
      resistance are necessary so that anti-malarial treatment strategies can be
      structured and implemented accordingly by the Malaria Control Program, Pakistan.
      This review aims to provide information on genetic markers of P. vivax population
      structure and drug resistance and comment on their usefulness in molecular
      surveillance and control. 

PMID- 24304993
TI  - Regional anaesthesia in thyroid surgery.
AB  - Thyroidectomy is usually performed under general anaesthesia with endotracheal
      intubation. Bilateral cervical plexus block has been occasionally used as sole
      anaesthesia technique for this operation in certain parts of world. Indications
      for regional anaesthesia elsewhere in the world are patient's preference and
      associated marked cardio-respiratory disease. This is the first report of
      thyroidectomy done solely under bilateral cervical plexus block in Pakistan. The
      patient had thyroid cancer and was medically compromised due to cardiac failure
      with ejection fraction of 25%. Bilateral cervical plexus block was performed to
      avoid the high risk with general anaesthesia. Total thyroidectomy was done while
      patient remained painfree during the procedure and top-up local anaesthetic
      infiltration was not required. Patient remained stable without any morbidity.
      Positive experience from this case indicates that regional anaesthesia with
      monitored anaesthesia care is safer than general anaesthesia in high risk
      patients and could be offered to selective thyroidectomy candidates. 

PMID- 24304994
TI  - Backache due to alkaptonuria in a middle aged man.
AB  - Alkaptonuria is a rare cause of backache. A 55 years old gentleman, a retired
      army personal had been having pain and stiffness in the spine for the last 15
      years, accompanied by bluish black discolouration of face and hands. Kyphosis and
      reduced movement of spine were present. Other joints were spared. Osler spots
      were visible on the sclera. X-rays revealed calcification of intervertebral
      discs. Asymptomatic renal stone was identified. There was no cardiac involvement.
      Symptomatic care was provided. 

PMID- 24304995
TI  - Successful treatment of hydatid cyst of lesser sac with PAIR therapy.
AB  - Hydatid disease has varied presentations and may involve any part of the body
      with hydatid disease of the liver being the most common site. Hydatid disease of
      lesser sac is a rare entity. Different treatment options of hydatid liver disease
      are available which include surgical, medical and radiological management.
      Surgical management has its limitations in terms of cost, morbidity, mortality,
      rate of recurrence and patient fitness to undergo surgery. Medical management
      alone carries a low chance of cure. Radiological management with PAIR therapy
      (percutaneous aspiration, injection and re-aspiration) of hydatid liver disease
      has been well described in literature. However, hydatid disease of lesser sac in
      itself is a rare entity and its treatment with PAIR procedure has not been
      described before. We describe a case of hydatid disease of lesser sac treated
      with the PAIR procedure. 

PMID- 24304996
TI  - Bacteremia due to Aeromonas hydrophila in acute lymphoblastic leukemia.
AB  - Aeromonas hydrophila (A. hydrophila) is a low virulent organism but may cause
      devastating fatal infections in immunocompromised host especially in liver
      cirrhosis. It is rarely reported to cause septicemia in a patient with Acute
      Lymphoblastic Leukemia (ALL). The mortality rate of septicemia due to A.
      hydrophila is 29% to 73%. We report a case of 59-year-old female patient who was
      a known case of ALL, presented with the complaints of fever, lethargy and
      generalized weakness for one month. After taking blood samples for
      investigations, empirical antimicrobial therapy was started. She did not improve
      after 48 hours of therapy. Meanwhile blood culture revealed pure growth of A.
      hydrophila. After sensitivity report was available, ciprofloxacin was started.
      Patient became afebrile after 48 hours of treatment with ciprofloxacin. It is
      very vital to correctly identified and treat bacteremia due to A. hydrophila
      especially in the underlying leukemic patient. 

PMID- 24304997
TI  - A five years old girl child with Takayasu arteritis.
AB  - Takayasu arteritis is a systemic vasulitis of large vessels that mainly involves
      the aorta and its branches. It normally presents in third decade of life and has
      rarely been reported in children under 10 years of age. We report here a case of
      Takayasu arteritis in a 5 years old girl who presented with headache, generalized
      body swelling, severe hypertension, proteinuria and minimal functioning kidneys.
      Conventional angiography demonstrated narrowing of descending aorta, right
      subclavian artery and right common iliac artery. She responded steroids,
      diuretics, antiplatelets and digoxin and discharged home on maintenance therapy. 

PMID- 24304998
TI  - Prosthodontic management of a patient with ectodermal dysplasia.
AB  - Ectodermal dysplasia is a rare congenital disease that affects the ectodermal
      structures. It is characterized by hypotrichosis, hypohidrosis and hypodontia. A
      14-year-old boy with ectodermal dysplasia presenting with oligodontia and marked
      resorption of the maxillary and mandibular alveolar ridges is reported.
      Prosthetic rehabilitation in the form of a maxillary and mandibular partial
      denture was made with metal crowns on existing lower teeth to achieve appropriate
      vertical dimension. Significant improvement in speech, masticatory function and
      facial esthetics was achieved. Removable prosthodontics can provide an acceptable
      solution to esthetic, functional and psychological rehabilitation in patients
      with ectodermal dysplasia. 

PMID- 24304999
TI  - Bilateral miliary shadowing on chest X-ray.
AB  - A patient presented with recent onset of increasing shortness of breath, weight
      loss and low-grade fever. His chest X-ray revealed bilateral miliary shadowing.
      He was investigated with CT-scanning of thorax. Later, a biopsy from supra
      clavicular node and its immunocytochemistry studies confirmed metastasis from
      primary lung cancer. Primary lung cancer with miliary pulmonary metastases is a
      rare happening and is mostly associated with lung adenocarcinoma. 

PMID- 24305000
TI  - The effect on student performance of scrambling questions and their stems in
      medical colleges admission tests.
AB  - Assessment is an indispensable part of an educational program. Multiple Choice
      Questions (MCQs) is an objective tool of assessment provided cheating is
      controlled. A method employed to reduce the chance of cheating is to scramble the
      sequence of the MCQs and responses in multiple papers having the same content. It
      is assumed that the performance of students is mainly dependent on the difficulty
      of the items and not the order in which they are placed within the instrument.
      The marks obtained by 1,02,211 candidates sitting in Medical Colleges Admission
      Test (MCAT) from 2008 to 2011 and given similar-content but scrambled-sequence
      question paper codes were analyzed using parametric tests. A significant
      difference amongst the mean marks of candidates in the different codes of MCAT
      2008 (F = 22.15, p < 0.001) and MCAT 2011 (F = 3.85, p = 0.009) was identified.
      No significant difference was found in the mean marks of the candidates' each
      year for different codes in each centre. 

PMID- 24305001
TI  - Polio eradication in Pakistan: the real reason for our failure.

PMID- 24305002
TI  - Commercialization of gene therapy drugs.

PMID- 24305006
TI  - Retraction notice.

PMID- 24305008
TI  - Validation of a histology-independent prognostic gene signature for early-stage,
      non-small-cell lung cancer including stage IA patients.
AB  - BACKGROUND: Patients with early-stage non-small-cell lung carcinoma (NSCLC) may
      benefit from treatments based on more accurate prognosis. A 15-gene prognostic
      classifier for NSCLC was identified from mRNA expression profiling of tumor
      samples from the NCIC CTG JBR.10 trial. In this study, we assessed its value in
      an independent set of cases. METHODS: Expression profiling was performed on RNA
      from frozen, resected tumor tissues corresponding to 181 stage I and II NSCLC
      cases collected at University Health Network (UHN181). Kaplan-Meier methodology
      was used to estimate 5-year overall survival probabilities, and the prognostic
      effect of the classifier was assessed using the log-rank test. A Cox proportional
      hazards model evaluated the signature's effect adjusting for clinical prognostic
      factors. RESULTS: Expression data of the 15-gene classifier stratified UHN181
      cases into high- and low-risk subgroups with significantly different overall
      survival (hazard ratio [HR] = 1.92; 95% confidence interval [CI], 1.15-3.23; p =
      0.012). In a subgroup analysis, this classifier predicted survival in 127 stage I
      patients (HR = 2.17; 95% CI, 1.12-4.20; p = 0.018) and the smaller subgroup of 48
      stage IA patients (HR = 5.61; 95% CI, 1.19-26.45; p = 0.014). The signature was
      prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR = 1.76,
      p = 0.058; HR = 4.19, p = 0.045, respectively). CONCLUSION: The prognostic
      accuracy of a 15-gene classifier was validated in an independent cohort of 181
      early-stage NSCLC samples including stage IA cases and in different NSCLC
      histologic subtypes.

PMID- 24305007
TI  - Analysis of MicroRNAs in sputum to improve computed tomography for lung cancer
      diagnosis.
AB  - INTRODUCTION: Computed tomography (CT) plays a central role in lung cancer
      diagnosis. However, CT has relatively low specificity, presenting a challenge in
      clinical settings. We previously identified 12 microRNAs (miRNAs) whose
      expressions in tumor tissues were associated with lung cancer. METHODS: Using
      quantitative reverse transcriptase polymerase chain reaction, we aimed to
      identify miRNA biomarkers in sputum that could complement CT for diagnosis of
      lung cancer. RESULTS: In a training set consisting of 66 lung cancer patients and
      68 cancer-free smokers, 10 of the 12 miRNAs were differentially expressed between
      the cases and controls (p <= 0.01). From the miRNAs, a logistic regression model
      was built on the basis of miR-31 and miR-210, both of which had the best
      prediction for lung cancer, producing an area under receiver operating
      characteristic curve of 0.83. Combined use of the two miRNAs yielded 65.2%
      sensitivity and 89.7% specificity, CT had 93.9% sensitivity and 83.8% specificity
      for lung cancer diagnosis. Notably, combined analysis of the miRNA biomarkers and
      CT produced a higher specificity than does CT used alone (91.2% versus 83.8%; p <
      0.05). The diagnostic performance of the biomarkers was confirmed in a testing
      set comprising 64 lung cancer patients and 73 cancer-free smokers. CONCLUSION:
      The sputum miRNA biomarkers might be useful in improving CT for diagnosis of lung
      cancer, but further independent validation on an external and prospective cohort
      of patients is required.

PMID- 24305009
TI  - Positive prognostic impact of miR-210 in non-small cell lung cancer.
AB  - OBJECTIVES: miR-210 is an important regulator of the cellular response to
      hypoxia. Therefore, we aimed to explore the prognostic significance of miR-210 in
      non-small cell lung cancer (NSCLC) patients with stage I-IIIA disease. MATERIALS
      AND METHODS: In addition to clinicopathological and demograpic information, tumor
      tissues were collected and tissue micro arrays (TMAs) were constructed from 335
      patients with stage I-IIIA NSCLC. Expression of miR-210 in cancer cells and
      stromal cells of the tumor was assessed by in situ hybridization. RESULTS: In
      univariate analyses, high cancer cell (p=0.039) and high stromal cell expression
      (p=0.008) of miR-210 were both significantly associated with an improved disease
      spesific survival (DSS). High co-expression of miR-210 in cancer and stromal
      cells was also a positive prognostic factor for DSS (p=0.010). In multivariate
      analysis, miR-210 in stromal cells (p=0.011), and miR-210 co-expressed in cancer
      and stromal cells was an independent prognosticator for DSS (p=0.011).
      CONCLUSIONS: We show that miR-210 in stromal cells, and co-expressed in cancer
      cells and stromal cells mediates an independent prognostic impact. It is a
      candidate marker for prognostic stratification in NSCLC.

PMID- 24305010
TI  - Antifungal susceptibility and growth inhibitory response of oral Candida species
      to Brucea javanica Linn. extract.
AB  - BACKGROUND: Candida species have been associated with the emergence of resistant
      strains towards selected antifungal agents. Plant products have been used
      traditionally as alternative medicine to ease candidal infections. The present
      study was undertaken to investigate the antifungal susceptibility patterns and
      growth inhibiting effect of Brucea javanica seeds extract against Candida
      species. METHODS: A total of seven Candida strains that includes Candida albicans
      ATCC14053, Candida dubliniensis ATCCMYA-2975, Candida glabrata ATCC90030, Candida
      krusei ATCC14243, Candida lusitaniae ATCC64125, Candida parapsilosis ATCC22019
      and Candida tropicalis ATCC13803 were used in this study. The antifungal
      activity, minimum inhibitory concentration and minimum fungicidal concentration
      of B. javanica extract were evaluated. Each strain was cultured in Yeast Peptone
      Dextrose broth under four different growth environments; (i) in the absence and
      presence of B. javanica extract at respective concentrations of (ii) 1 mg/ml
      (iii) 3 mg/ml and (iv) 6 mg/ml. The growth inhibitory responses of the candidal
      cells were determined based on changes in the specific-growth rates (MU) and
      doubling time (g). The values in the presence of extract were computed as
      percentage in the optical density relative to that of the total cells suspension
      in the absence of extract. RESULTS: B. javanica seeds extract exhibited
      antifungal properties. C. tropicalis showed the highest growth rate; 0.319 +/-
      0.002 h(-1), while others were in the range of 0.141 +/- 0.001 to 0.265 +/- 0.005
      h(-1). In the presence of extract, the lag and log phases were extended and
      deviated the MU- and g-values. B. javanica extract had significantly reduced the
      MU-values of C. dubliniensis, C. krusei and C. parapsilosis at more than 80% (rho
      < 0.05), while others were reduced within the range of 2.28% to 57.05%. The g
      values of most candidal strains were extended and significantly reduced (rho <
      0.05) in relative to the untreated. The candidal population was reduced from an
      average of 10 x 106 to 6 x 106 CFU/ml. CONCLUSIONS: B. javanica extract exhibited
      in vitro antifungal activity against seven oral Candida species. The fungistatic
      and growth inhibiting effects of B. javanica extract have shown that it has
      potential to be considered as a promising candidate for the development of
      antifungal agent in oral health products.

PMID- 24305011
TI  - Specific expression of foreign gene in postnatal mouse glial cells using
      electroporation.

PMID- 24305012
TI  - Brain metastasis from invasive thymoma mimicking intracerebral hemorrhage: case
      report.
AB  - A 55-year-old man with an 8-year history of invasive thymoma presented with
      sudden onset of left hemiparesis. Computed tomography (CT) and magnetic resonance
      (MR) imaging showed a right frontal lobe intracerebral hemorrhage and the
      possibility of brain metastasis could not be rejected. The patient underwent
      removal of the hematoma. Histological examination showed brain metastasis from
      invasive thymoma. To the best of our knowledge, this is the first reported case
      of hemorrhagic brain metastasis from invasive thymoma (non-cancerous) mimicking
      intracerebral hemorrhage. 

PMID- 24305013
TI  - Arachnoid cyst in the middle cranial fossa presenting with pulsatile
      exophthalmos: case report and literature review.
AB  - A 20-year-old woman suffered gradual progression of right pulsatile exophthalmos
      and slight headache. Computed tomography (CT) demonstrated outward and downward
      displacement of the right globe and an arachnoid cyst in the right middle cranial
      fossa associated with thinned and anterior protrusion of a bony orbit.
      Microscopic cystocisternotomy was performed and the cerebrospinal fluid (CSF)
      inside of the cyst communicated into the carotid cistern and cistern in the
      posterior cranial fossa. Pulsatile exophthalmos improved immediately after
      surgery. Arachnoid cyst in the middle cranial fossa presenting with exophthalmos
      is rare. Microscopic cystocisternotomy might successfully improve CSF flow and
      relieve exophthalmos. 

PMID- 24305014
TI  - Intracranial meningioma as initial clinical manifestation of occult lung
      carcinoma: case report.
AB  - Intracranial meningioma with intratumor metastasis have been occasionally
      reported. However, to our knowledge, there are almost no reports of malignant
      tumors initially discovered due to metastasis to meningioma. A 74-year-old woman
      presented with amnesia. Magnetic resonance imaging showed a well-defined mass
      arising from falcotentorial junction and homogeneous enhancement. Histopathologic
      findings showed that the mass was a meningothelial meningioma, with the majority
      of the tumor cells propagating in sheets, however, a single area in the tumor
      tissue showed the different histology. Immunohistologically, cytokeratin 7 (CK7),
      thyroid transcription factor-1 (TTF-1), and Napsin were positive, which led to
      lung adenocarcinoma metastasis. Furthermore, E-cadherin staining showed a 70%
      positive rate in lung adenocarcinoma and 30% in meningothelial meningioma. We
      report our experiences regarding a case of lung cancer that metastasized to
      intracranial meningioma and its clinical presentation and pathology. 

PMID- 24305015
TI  - A new mechanism of cerebrospinal fluid leakage after lumboperitoneal shunt: a
      theory of shunt side hole--case report.
AB  - Cerebrospinal fluid (CSF) overdrainage after lumboperitoneal (LP) shunt placement
      for the patients with idiopathic normal pressure hydrocephalus (iNPH) is mainly
      caused by insufficient management of pressure settings of the shunt valve and/or
      siphon effect of shunt systems induced by the patient's postural changes. We here
      report a unique case of intracranial hypotension (IH) due to CSF leakage after LP
      shunt placement in which another mechanism leads to the CSF leakage. A 67-year
      old man suffered from persistent headache worsening with postural change 2 months
      after LP shunt reconstruction for iNPH. Brain computed tomography scan showed
      bilateral chronic subdural hematomas (CSDH). Lumbar images including shuntography
      and magnetic resonance imaging showed the tip of the lumbar catheter was
      spontaneously pulled out close to the dura mater with expansion of the epidural
      space due to CSF leakage from a shunt side hole of the lumbar catheter to the
      epidural space. Shunt removal and subsequent irrigation of CSDH improved his
      headache. CSF leakage in our case differs from those in previous reports, because
      early and enormous CSF leakage into the epidural space can be explained only by a
      different mechanism through a side hole just located in the epidural space in our
      case. We must pay attention to the possibility of this rare cause of IH due to
      CSF leakage in patients suffering from postural headache after LP shunt
      placement. 

PMID- 24305016
TI  - Pneumocephalus and pneumorrhachis after spinal surgery: case report and review of
      the literature.
AB  - Trauma is a common cause of pneumocephalus, or air in the cranial cavity, and of
      pneumorrhachis, or the presence of intraspinal air. After spinal surgery,
      occurrence of pneumocephalus, especially with pneumorrhachis, is extremely rare.
      We report the case of a patient who developed pneumocephalus and pneumorrhachis
      after lumbar disc surgery and pedicle screw fixation. There was no cerebrospinal
      fluid leakage during surgery. On postoperative day 1, the patient complained of
      headache, nausea, and dizziness. Brain and lumbar computed tomography scans
      revealed pneumocephalus and pneumorrhachis. With conservative treatment, the
      patient's complaints resolved within 10 days. 

PMID- 24305017
TI  - Relation between the persistence of an abnormal muscle response and the long-term
      clinical course after microvascular decompression for hemifacial spasm.
AB  - Mentalis muscle responses to electrical stimulation of the zygomatic branch of
      the facial nerve are considered abnormal muscle responses (AMRs) and can be used
      to monitor the success of decompression in microvascular decompression (MVD)
      surgery. The aim of this study was to compare the long-term outcome of MVD
      surgery in which the AMR disappeared to the outcome of surgery in which the AMR
      persisted. From 2005 to 2009, 131 patients with hemifacial spasm received MVD
      surgery with intraoperative monitoring of AMR. At 1 week postsurgery, spasms had
      resolved in 82% of cases in the AMR-disappearance group and 46% of cases in the
      persistent-AMR group, mild spasms were present in 10% of cases in the AMR
      disappearance group and 31% of cases in the persistent-AMR group, and moderate
      were present spasms in 8% of cases in the AMR-disappearance group and 23% of
      cases in the persistent-AMR group (P < 0.05). At 1 year postsurgery, spasms had
      resolved in 92% of cases in the AMR-disappearance group and 84% of cases in the
      persistent-AMR group, mild spasms were present in 6% of cases in the AMR
      disappearance group and 8% of cases in the persistent-AMR group, and moderate
      spasms were present in 3% of cases in the AMR-disappearance group and 8% of the
      cases in the persistent-AMR group (P = 0.56). These results indicate that the
      long-term outcome of MVD surgery in which the AMR persisted was no different to
      that of MVD surgery in which the AMR disappeared. 

PMID- 24305018
TI  - Endovascular treatment of spinal vascular lesion in Japan: Japanese Registry of
      Neuroendovascular Therapy (JR-NET) and JR-NET2.
AB  - A subgroup analysis of spinal vascular lesions in the Japanese Registry of
      Neuroendovascular Therapy (JR-NET) and JR-NET2, retrospective registry studies
      conducted in 2005-2009, was performed to understand the current status of
      treatment in Japan. Of 201 spinal lesions enrolled, 98 analyzable cases of spinal
      dural arteriovenous fistula (SDAVF), 43 of spinal perimedullary arteriovenous
      fistula (SPAVF), and 23 of spinal intramedullary arteriovenous malformation
      (SIAVM) were assessed. Treatment was radical in the majority (83.6%) of SDAVF,
      palliative in the majority (70.6%) of SIAVM, and radical and palliative in a
      similar number of cases of SPAVF. Total occlusion was achieved in 26 (54.2%)
      SDAVF cases, 9 (29.0%) SPAVF, and 4 (23.5%) SIAVM. Treatment-related
      complications occurred in 3 (3.1%) SDAVF cases, 7 (16.3%) SPAVF, and 1 (4.3%)
      SIAVM. Post-treatment neurological improvement was achieved in 49 (50.0%) of
      SDAVF cases, 15 (34.9%) SPAVF, and 5 (21.7%) SIAVM. The modified Rankin Scale
      (mRS) of 0, 1, or 2 on postoperative day 30, the primary endpoint, was achieved
      in 62 (63.3%) SDAVF cases, 26 (60.5%) SPAVF, and 12 (52.2%) SIAVM. The mRS of 0-2
      on postoperative day 30 was correlated with presymptomatic mRS of 0-2 [P <
      0.0001, odds ratio (OR): 42.88, 95% confidence interval (CI): 14.83-123.97] and
      postoperative neurological improvement (P = 0.046, OR: 2.57, 95% CI: 1.02-6.48).
      In Japan, endovascular treatment of spinal vascular lesions was administered
      safely. Good mRS on postoperative day 30 was highly correlated with good pre
      symptomatic mRS, suggesting necessity of early diagnosis and treatment. 

PMID- 24305019
TI  - Delayed cerebrospinal fluid leak after watertight dural closure with a
      polyethylene glycol hydrogel dural sealant in posterior fossa surgery: case
      report.
AB  - A polyethylene glycol (PEG) hydrogel sealant recently has been approved as an
      adjunct to sutured dural closure in Japan. We treated consecutive six patients
      with PEG hydrogel sealant in posterior fossa operation. Three of six cases
      suffered delayed cerebrospinal fluid (CSF) leak after watertight dural closure
      with the PEG hydrogel sealant, although there was no leak case which was treated
      with fibrin glue, before 2 years until the adoption of the new material. These
      patients underwent posterior fossa craniotomy and discharged without remarkable
      CSF leak. The pseudomeningocele under the occipital wound caused the CSF leak
      occurr from 5th to 7th week postoperatively. All CSF leak cases needed surgical
      repair. At the repair, the PEG hydrogel was liquefied and almost absorbed. A
      fistula on the closure line and a dead space after the absorption of the PEG
      hydrogel was observed. When the absorbable PEG hydrogel sealant plugs in small
      gaps of sutured dura, its properties to prevent adhesion might suppress healing
      process of dural closure, so that CSF could leak through the gaps and collect as
      a pseudomeningocele in the dead space after absorption of the PEG hydrogel. In
      posterior fossa surgery a PEG hydrogel sealant should be applied when dural edges
      are closed tightly without any gaps. 

PMID- 24305020
TI  - A case of presumably Rathke's cleft cyst associated with postoperative
      cerebrospinal fluid leakage through persisting embryonal infundibular recess.
AB  - Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third
      ventricular floor. Only eight cases have been published. In this report, a case
      of presumably Rathke's cleft cyst associated with cerebrospinal fluid leakage
      caused by PEIR is described. An 81-year-old woman underwent endoscopic
      transsphenoidal surgery for the intra- and supra-sellar cystic lesion.
      Intraoperatively a hole was confirmed over the sella turcica connecting the
      sellar cyst and the infundibular recess. Liquorrhea did not occur throughout the
      procedure. A computed tomography (CT) scan obtained immediately after surgery
      disclosed accumulation of air in the third and lateral ventricles, in addition to
      the intra- and supra-sellar region. Air accumulation resolved spontaneously after
      bed rest for 11 days and she was discharged without neurological deficits.
      However, she required the second transsphenoidal surgery to repair the sellar
      floor because of bacterial meningitis caused by liquorrhea on the postoperative
      day 23. A postoperative 3-tesla magnetic resonance image revealed a deep
      infundibular recess connecting the sella turcica and the third ventricle, which
      was considered to be PEIR. To the best our knowledge, this is the first reported
      case describing the intraoperative findings of PEIR. 

PMID- 24305021
TI  - Three cases of spontaneous superficial temporal artery aneurysm with literature
      review.
AB  - Spontaneous, nontraumatic, superficial temporal artery (STA) aneurysms have been
      rarely reported. We herewith report three cases of spontaneous and true STA
      aneurysms. All patients, a 65-year-old male, a 76-year-old female, and a 47-year
      old female, had no history of head trauma that requires medical attention.
      Painless, pulsatile, and slowly growing calvarial lump was the symptom leading to
      image studies. All the lumps were preoperatively diagnosed as STA aneurysms by
      magnetic resonance angiography and/or three-dimensional computed tomographic
      angiography. One case was accompanied by anterior communicating aneurysm. And
      another case was associated with two more scalp aneurysms arising from occipital
      artery and contralateral STA. Pathologic studies showed that all three were true
      aneurysms, with intact media and adventitia but without organized hematoma.
      Literature review showed that 8% of all STA aneurysms comprised spontaneous STA
      aneurysms. We found 32 cases (19 males and 13 females) of well-described
      spontaneous STA aneurysms including ours. Twenty-eight cases (87.5%) were true
      aneurysms. Seven cases (21.9%) had coexisting vascular lesions. Five (15.6%) of
      these seven cases were diagnosed with cerebral or abdominal aneurysm. Multiple
      scalp aneurysms are quite rare; only two cases including ours have been reported.
      It seems important to know that spontaneous STA aneurysms may coexist with other
      vascular lesions including intracranial aneurysm. 

PMID- 24305022
TI  - Long-term survival of diffuse large B cell lymphoma of the trigeminal region
      extending to the Meckel's cave treated by CHASER therapy: case report.
AB  - A 52-year-old man with a history of malignant lymphoma of the cecum presented
      with lancinating facial pain in the left. Magnetic resonance imaging (MRI)
      revealed a tumor in the Meckel's cave extending along the trigeminal nerve. The
      tumor was partially removed via left retrosigmoid lateral suboccipital
      craniotomy. Histological examination showed findings consistent with diffuse
      large B cell lymphoma, which was later confirmed to be metastatic lesion from the
      cecal lesion. Postoperative chemotherapy with cyclophosphamide, high dose,
      cytarabine, steroid (dexamethasone), etoposide, and rituximab (CHASER) followed
      by whole brain irradiation (30 Gy) resulted in complete remission. Although
      facial pain persisted, the patient's general condition remained favorable and he
      did not experience recurrence over the 51-month follow-up period. Histological
      confirmation and awareness of malignant lymphoma are very important to determine
      the therapeutic strategy and to avoid misdiagnosis or delayed diagnosis. Long
      term survival of patients with metastatic malignant lymphoma in the Meckel's cave
      extending along the trigeminal nerve was very rare. In addition, metastatic
      malignant lymphoma in the extra-axial and peripheral nervous tissue might be
      different from primary central nervous system lymphoma in the white matter, since
      the efficacy of chemotherapeutic agents against malignant lymphomas in the extra
      axial regions is not attenuated by the blood brain barrier. 

PMID- 24305023
TI  - Two cases of subfrontal schwannoma, including a rare case located between the
      endosteal and meningeal layers of the dura.
AB  - Subfrontal schwannomas arising from the olfactory groove are rare and their
      origin remains uncertain because olfactory bulbs do not possess Schwann cells. We
      present two cases of subfrontal schwannomas treated with surgical resection. In
      one case, the tumor was located between the endosteal and meningeal layers of the
      dura mater. This rare case suggests that subfrontal schwannomas may originate
      from the fila olfactoria. 

PMID- 24305024
TI  - Functional localization of the supplementary motor area.
AB  - The supplementary motor area (SMA) is a key structure involved in behavioral
      planning and execution. Although many reports have indicated that SMA is
      organized somatotopically, its exact organization remains still unclear. This
      study aimed to functionally map SMA using functional magnetic resonance imaging
      (fMRI) and validate the fMRI-SMA by electrocortical stimulation (ECS) and
      postsurgical symptoms. Total 32 healthy volunteers and 24 patients participated
      in this study. Motor tasks were right and left finger tapping and language tasks
      included simple reading, lexical decision for presented words, and verb
      generating tasks. SPM8 was used to conduct individual and group analyses. In all
      subjects, the lexical decision task induced the greatest number of active fMRI
      pixels in SMA. fMRI during the language tasks showed anterior part of SMA
      compared to finger tapping tasks. We found an overlap spot with all different
      tasks in posterior part of SMA, which we termed SMA core. Six patients underwent
      awake craniotomy for ECS mapping for primary regions and SMA. During awake
      craniotomy, ECS to posterior part of SMA, which might involve the possible SMA
      core consistently, evoked both speech arrest and flaccid hemiparesis. The SMA
      mapping suggested posterior part of SMA might play more important roles in any
      executions, which might involve the SMA core. 

PMID- 24305025
TI  - Changes in the coagulation and fibrinolytic system of patients with subarachnoid
      hemorrhage.
AB  - The aim of this study was to investigate the dynamic changes in the coagulation
      and fibrinolytic system with subarachnoid hemorrhage. The blood coagulation
      enzyme-AT complex (TAT), anticoagulant enzyme (AT), tissue plasminogen activator
      (tPA), plasminogen activin inhibitor (PAI-1), and mean blood flow velocity were
      measured. The TAT level was significantly higher 6 h after subarachnoid
      hemorrhage (SAH), whereas AT was significantly lower. These changes were
      maintained at 12 h to 1 d after SAH, returned to normal at 3 d, significantly
      changed again at 7 d to 14 d. The tPA level gradually increased after SAH and
      peaked at 14 d, and then returned to normal at 21 d. The PAI-1 levels were
      significantly lower than those in the control group 1 d after SAH gradually
      increased, and returned to normal at 21 d. In the cerebral vasospasm (CVS)
      groups, the levels of TAT, and AT significantly changed compared to the non-CVS
      groups after SAH. The PAI-1 levels were higher at 7 d and 14 d, but the changes
      were not significant. In groups Fisher III and IV as well as Hunt III to V, the
      TAT, AT, tPA, and PAI-1 levels were significantly higher than those in both
      Fisher and Hunt I and II 6 h, 12 h, 1 d, 7 d, and 14 d after SAH. The changes in
      the coagulation and fibrinolytic system of patients with SAH are correlated with
      the progress and symptoms of SAH as well as the blood content and CVS. 

PMID- 24305026
TI  - Expression of the TGF-beta-ALK-1 pathway in dura and the outer membrane of
      chronic subdural hematomas.
AB  - Neovascularization of the outer membrane plays a critical role in the development
      and enlargement of chronic subdural hematomas (CSHs) and vascular endothelial
      growth factor (VEGF) may promote their progression. However, the precise
      mechanisms remain to be determined. We focused on the signaling pathway upstream
      of VEGF, transforming growth factor beta (TGF-beta), and activin receptor-like
      kinase 1 (ALK-1) to identify the mechanisms underlying the neovascularization of
      the outer membrane of CSH. Retrospective comparative study was conducted on 15
      consecutive patients diagnosed as CSH with burr-hole drainage. Dura and the outer
      membrane were collected. We immunohistochemically examined the expression of
      VEGF, integrin-alpha, TGF-beta, and ALK-1 on the outer membrane and dura of CSH
      and compared our findings with control samples and the signal intensity of
      hematomas on computed tomography (CT) scans. VEGF and integrin-alpha expression
      was markedly up-regulated in both the dura and outer membrane of CSH, the
      expression of TGF-beta and ALK-1 in the dura was slightly increased in the dura
      and markedly up-regulated in the outer membrane. There was no significant
      correlation between their expression and CT density. Here we first report the
      expression of TGF-beta and ALK-1 in the outer membrane and dura mater of CSH. We
      suggest that the TGF-beta-ALK-1 pathway and VEGF affect neovascularization and
      the progression of CSH. 

PMID- 24305027
TI  - Primary enlarged craniotomy in organized chronic subdural hematomas.
AB  - The aim of the study is to evaluate the efficacy of craniotomy and membranectomy
      as initial treatment of organized chronic subdural hematoma (OCSH). We
      retrospectively reviewed a series of 34 consecutive patients suffering from OCSH,
      diagnosed by magnetic resonance imaging (MRI) or contrast computer tomography
      (CCT) in order to establish the degree of organization and determine the
      intrahematomal architecture. The indication to perform a primary enlarged
      craniotomy as initial treatment for non-liquefied chronic subdural hematoma
      (CSDH) with multilayer loculations was based on the hematoma MRI appearance-
      mostly hyperintense in both T1- and T2-weighted images with a hypointense web- or
      net-like structure within the hematoma cavity. The reason why some hematomas
      evolve towards a complex and organized architecture remains unclear; the most
      common aspect to come to light was the "long standing" of the CSDHs which, in our
      series, had an average interval of 10 weeks between head injury and initial scan.
      Recurrence was found to have occurred in 2 patients (6% of cases) in the form of
      acute subdural hematoma. One patient died as the result of an intraventricular
      and subarachnoid haemorrhage, while 2 patients (6%) suffered an haemorrhagic
      stroke ipsilateral to the OCSH. Eighty-nine percent of cases had a good recovery,
      while 11% remained unchanged or worsened. In select cases, based on the MRI
      appearance, primary enlarged craniotomy seems to be the treatment of choice for
      achieving a complete recovery and a reduced recurrence rate in OCSH.

PMID- 24305028
TI  - Comparison of (11)C-methionine, (11)C-choline, and (18)F-fluorodeoxyglucose-PET
      for distinguishing glioma recurrence from radiation necrosis.
AB  - The aim of this study is to assess the different metabolic activities
      characteristic of glioma recurrence and radiation necrosis (RN) and to explore
      the diagnostic accuracy for differentiation of the two conditions using (11)C
      methionine (MET), (11)C-choline (CHO), and (18)F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET). Fifty patients with lesions suggestive of
      recurrent glioma by MRI underwent MET, CHO, and FDG-PET. All patients who had
      previously been treated with radiotherapy for malignant glioma were subjected to
      open surgery and pathological diagnosis (17 recurrent grade 3- gliomas (Gr.3s)
      comprising 7 anaplastic astrocytomas (AAs) and 10 anaplastic oligodendrogliomas
      (AOs), 17 recurrent glioblastomas (Gr.4s), and 16 RNs). We measured the PET/Gd
      volume ratio, the PET/Gd overlap ratio, and the lesion/normal brain uptake ratio
      (L/N ratio) and determined the optimal index of each PET scan. The PET/Gd volume
      ratio and the PET/Gd overlap ratio for RN were significantly lower than those of
      glioma recurrence only with MET-PET (P < 0.05). The L/N ratio of RN was
      significantly lower than that of Gr.4 with all PET imaging (P < 0.001) and was
      significantly lower than that of Gr.3, especially for AO, only with MET-PET
      images (P < 0.005). Receiver operating characteristic (ROC) analysis showed that
      the area under the curve of MET, CHO, and FDG was 92.5, 81.4, and 77.4,
      respectively. MET L/N ratio of greater than 2.51 provided the best sensitivity
      and specificity for establishing glioma recurrence (91.2% and 87.5%,
      respectively). These results demonstrated that MET-PET was superior to both CHO
      and FDG-PET for diagnostic accuracy in distinguishing glioma recurrence from RN. 

PMID- 24305029
TI  - Current perioperative management of anticoagulant and antiplatelet use in
      neuroendovascular therapy: analysis of JR-NET1 and 2.
AB  - To evaluate current perioperative antithrombotic management in neuroendovascular
      therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in
      various procedures and examined their relationships with periprocedural adverse
      events. Patient's data from nationwide surveys administered by the Japanese
      Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December
      2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively
      analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet
      therapy and dual or triple therapy were increased for either aneurysm coiling and
      percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic
      complications were significantly decreased (4.2% vs. 2.1%, p < 0.001),
      hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5%
      vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p <
      0.001) were significantly increased in JR-NET2. The rate of hemorrhagic
      complications was significantly higher in patients with triple or more
      perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001,
      postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy
      was performed more frequently and intensively in neuroendovascular therapy in
      Japan. While ischemic complications were decreased, hemorrhagic complications and
      severe adverse events were increased. These results suggest that intensive
      antithrombotic therapy has a potential risk of hemorrhagic complications for
      Japanese patients. 

PMID- 24305030
TI  - Parent artery occlusion for unruptured cerebral aneurysms: the Japanese Registry
      of Neuroendovascular Therapy (JR-NET) 1 and 2.
AB  - Parent artery occlusion (PAO) is an alternative to surgical clipping or
      endovascular endosaccular coil embolization for the management of cerebral
      aneurysms. Most giant and fusiform aneurysms are not amenable to endosaccular
      coil embolization due to anatomical considerations, such as a broad-neck.
      However, majority of reports regarding the safety of PAO are based on case series
      involving a relatively small number of patients. In the present study, a total of
      381 consecutive patients with unruptured cerebral aneurysms who were treated with
      PAO were extracted from the Japanese Registry of Neuroendovascular Therapy (JR
      NET) 1 and JR-NET2 database, which are nationwide surveys conducted by the
      Japanese Society of Neuroendovascular Therapy. The mean age of the 381 patients
      was 58.1 years, and 59.3% were female. The aneurysmal location included the
      vertebral artery (42%) and the cavernous portion of internal carotid artery
      (32%). The aneurysm size and shape consisted of fusiform (45%), giant (25%), and
      large (22%). Symptomatic lesions were present in 59.8% of the population.
      Technical success was achieved in 98.4%. The 30-day morbidity and mortality rates
      were 3.1% and 1.0%, respectively. The most frequent procedure-related
      complication was ischemic stroke, which occurred in 12.9% (distal embolism, 6.0%;
      branch occlusion, 3.9%). The 30-day morbidity and mortality rates related to
      ischemic strokes were 2.1% and 0.3%, respectively. PAO for unruptured aneurysms
      is feasible with a high technical success rate. Peri-procedural management of
      ischemic stroke is the key to enhance the safety of this treatment option. 

PMID- 24305031
TI  - Real-world experience of carotid artery stenting in Japan: analysis of 7,134
      cases from JR-NET1 and 2 nationwide retrospective multi-center registries.
AB  - The present study aimed to demonstrate the "real-world" experiences of carotid
      artery stenting (CAS) in Japan using Japanese Registry of Neuroendovascular
      Therapy (JR-NET) 1 and 2, retrospective nationwide multi-center surveillances. JR
      NET1 and 2 registries are retrospective surveillances conducted between January
      2005 and December 2007 and January 2008 and December 2009, respectively, in Japan
      regarding neuroendovascular therapy. A total of 7,134 procedures (1,943 for JR
      NET1 and 5,191 for JR-NET2) were included in this study and retrieved data were
      analyzed retrospectively. Treatment results of two surveillance periods were
      similar. In JR-NET2 registry, total of 5,191 lesions were treated by CAS and
      5,008 of 5,191 procedures (96.5%) were performed by the board-certified surgeons
      of Japanese Society of Neuroendovascular Therapy. The rate of technical success
      was extremely high (99.99%), and the rate of clinically significant complication
      was low (3.2%). These results were comparable to a previous large study in Japan.
      Multivariate logistic analysis revealed that age [odds ratio (OR), 1.04 per year;
      95% confidence interval (CI), 1.02-1.07; p = 0.0004), symptomatic lesion (OR,
      1.87; 95% CI; p = 0.0004), and the use of closed-cell type stent (OR, 0.58; 95%
      CT, 0.32-1.00; p = 0.05) were independently associated with clinically
      significant complications. It was revealed that good clinical results were
      achieved in patients who underwent CAS in Japan. It is expected that the
      evolution of devices and increasing experiences of surgeons would lead to further
      improvement of the clinical results, and further investigation would be required
      to clarify the optimal treatment strategy and therapeutic efficacy of CAS,
      especially in symptomatic lesions. 

PMID- 24305032
TI  - Comparison of internal shunts during carotid endarterectomy under routine
      shunting policy.
AB  - We compared patients who underwent carotid endarterectomy (CEA) using two-way and
      three-way internal shunts and discussed which shunt was more appropriate and
      effective for surgeons. Eighty-two patients (mean 69.5 +/- 6.1 years old, mean
      degrees of stenosis 79.6 +/- 10.4%) who had undergone CEA by our routine shunting
      policy were examined concerning the difference of Sundt and Pruitt-Inahara (P-I)
      shunts in clinical use. Carotid clamping time for the P-I shunt was over 2
      minutes longer than that by Sundt in either split or conventional continuous
      arteriotomy (p < 0.001). The proportions of cases with multiple trials of either
      arteriotomy or insertion of a shunt tube, cases detected more than one high
      intensity spot on diffusion-weighted images of magnetic resonance imaging after
      CEA, and cases detected postoperative intimal flaps detected by multi-detector CT
      angiography showed no significant differences between the two shunt groups. The
      two-way Sundt shunt was quicker than the three-way P-I shunt in placement with no
      remarkable problems. Split arteriotomy was not useful in shortening the placement
      time for either Sundt or P-I shunt tubes, compared with continuous arteriotomy. A
      simple two-way shunt with easy handling like the Sundt shunt would be also
      appropriate to choose in selective shunting under the unfamiliarity of treating
      shunts. 

PMID- 24305033
TI  - Long-term effects of stimulants on neurocognitive performance of Taiwanese
      children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common
      behavioral and neurocognitive disorder in school-age children. Methylphenidate
      (MPH) is the most frequently prescribed CNS stimulant for ADHD. The aim of this
      study is to evaluate the changes in intelligence quotient and domains of
      neurocognitive function after long-term MPH treatment of Taiwanese children with
      ADHD. METHODS: The Wechsler Intelligence Scale (WISC-III) was administrated twice
      at an interval of at least one year for all 171 subjects (6-12 years) and 47 age-
      and gender-matched children without ADHD. The ADHD-Rating scale and Clinical
      Global Impression-Severity (CGI-S) were also used at the time of enrolment, and
      at 6 months and one year later. RESULTS: Taiwanese children with ADHD had lower
      Verbal IQ (VIQ) and Full IQ (FIQ) and performed poorly on several subtests of the
      WISC-III, including Similarities, Vocabulary, and Coding, compared to healthy
      children without ADHD. After one year of MPH treatment, significant decrements in
      all scores of the ADHD-Rating scale and CGI-S and increments in several domains
      of the WISC-III, including FIQ, VIQ, PIQ, Perceptual Organization Index (POI),
      Picture Completion, Picture Arrangement, Object Assembly, and Digit Span were
      observed. When the ADHD children under MPH treatment were subdivided into two age
      groups (6-8 years and 9-12 years), significantly better performance in some
      subtests and subscales of the WISC-III (such as Similarities, Comprehension, and
      Object assembly) was found in the 6-8 years age group. CONCLUSIONS: Long-term MPH
      treatment may improve the neurocognitive profiles of the ADHD children, as seen
      in their performance in several subtests and in the IQ scores on the WISC-III.
      And this improvement had no correlation with the decrement of ADHD symptoms.
      Starting stimulant treatment at as young an age as possible is advised due to the
      greater benefits in the 6-8 years age group, as seen in this study. More research
      in this area is also needed to confirm these results.

PMID- 24305034
TI  - BMJ is not always impartial about the advertisements it includes.

PMID- 24305035
TI  - Low Helicobacter pylori primary resistance to clarithromycin in gastric biopsy
      specimens from dyspeptic patients of a city in the interior of Sao Paulo, Brazil.
AB  - BACKGROUND: Clarithromycin, amoxicillin, and a pump proton inhibitor are the most
      common drugs recommended as first-line triple therapy for H.pylori treatment,
      which results in eradication rates close to 80%, varying regionally, principally
      due to emergency cases and increases of clarithromycin resistant strains.
      Nucleotide substitutions at the H. pylori domain V of the 23S rRNA fraction are
      involved in the macrolide resistance and the A2142G and A2143G mutations are
      predominant in clinical isolates worldwide including in Brazil. As H. pylori
      culture is fastidious, we investigated the primary occurrence of H. pylori A2142G
      and A2143G rDNA 23S mutations using a molecular approach directly on gastric
      biopsies of dyspeptic patients consecutively attended at Hospital das Clinicas of
      Marilia, Sao Paulo, Brazil. METHODS: Biopsy specimens obtained from 1137
      dyspeptic patients, were subjected to histopathology and H. pylori diagnosis by
      histology and PCR. PCR/RFLP assay was used to detect A2142G and A2143G point
      mutations at domain V of the H. pylori 23S rDNA associated with clarithromycin
      resistance. Through the developed assay, a 768 bp PCR amplicon corresponding
      to1728 to 2495 bp of the 23S H. pylori rDNA is restricted with MboII for A2142G
      mutation detection and with BsaI for A2143G mutation detection. Occurrence of 23S
      rDNA A2142G results in two DNA fragments (418 and 350 bp) and of 23S rDNA A2143G
      results in three DNA fragments (108, 310 and 350pb), due to a conserved BsaI
      restriction site. RESULTS: The PCR method used to diagnose H. pylori presented
      sensitivity, specificity and accuracy of 77,6%, 79,3% and 78,6%, respectively,
      compared to histology, the gold standard method for H. pylori diagnosis used in
      our routine. Prevalence of H.pylori with clarithromycin resistant genotypes was
      2,46%, with predominance of A2143G 23S rDNA point mutation. CONCLUSIONS: The
      PCR/RFLP assay was a rapid and accurate H.pylori diagnostic and clarithromycin
      resistance determination method useful for routine practice. As prevalence of
      primary resistance of H.pylori to clarithromycin due to A2142G and A2143G
      mutations remains low in Marilia, the standard clarithromycin containing triple
      therapy is still valid.

PMID- 24305036
TI  - Effectiveness of a multimodal treatment program for somatoform pain disorder.
AB  - Chronic pain conditions are highly prevalent, with somatoform pain disorder
      accounting for a large proportion. However, the psychological forms of treatment
      currently used achieve only small to medium effect sizes. This retrospective
      study investigated the effectiveness of a 5-week multimodal pain program for
      patients with somatoform pain disorder. The diagnosis of somatoform pain disorder
      was confirmed by a specialist for anesthesiology and pain management and a
      specialist for psychosomatic medicine. Therapy outcome was evaluated with a
      Numeric Rating Scale (NRS), the Pain Disability Index (PDI), and the Pain
      Perception Scale. Within the study sample (n = 100), all parameters showed a
      significant and clinically relevant improvement at the end of therapy (P values <
      0.001). The highest effect sizes (d) were found for reduction in average pain
      rating (NRS: d = 1.00) and the affective items of the Pain Perception Scale (SES
      A: d = 0.07). The lowest effect sizes were found for improvement of pain-related
      disabilities (PDI: d = 0.42) and sensory items of the Pain Perception Scale (SES
      S: d = 0.50). Despite high chronification of pain condition, with average pain
      duration of greater than 8 years, the multimodal treatment program showed medium
      to large effect sizes on the outcome of patients with somatoform pain disorder.
      Compared with previous data with small to moderate effect sizes, a multimodal
      program seems to be more effective than other interventions to address somatoform
      pain disorder.

PMID- 24305037
TI  - In search of compassion: a new taxonomy of compassionate physician behaviours.
AB  - BACKGROUND: Compassion has been extolled as a virtue in the physician-patient
      relationship as a response to patient suffering. However, there are few studies
      that systematically document the behavioural features of physician compassion and
      the ways in which physicians communicate compassion to patients. OBJECTIVE: To
      develop a taxonomy of compassionate behaviours and statements expressed by the
      physician that can be discerned by an outside observer. DESIGN: Qualitative
      analysis of audio-recorded office visits between oncologists and patients with
      advanced cancer. SETTING AND PARTICIPANTS: Oncologists (n = 23) and their
      patients with advanced cancer (n = 49) were recruited in the greater Rochester,
      New York, area. The physicians and patients were surveyed and had office visits
      audio recorded. MAIN OUTCOME MEASURES: Audio recordings were listened to for
      qualitative assessment of communication skills. RESULTS: Our sensitizing
      framework was oriented around three elements of compassion: recognition of the
      patient's suffering, emotional resonance and movement towards addressing
      suffering. Statements of compassion included direct statements, paralinguistic
      expressions and performative comments. Compassion frequently unfolded over the
      course of a conversation rather than being a single discrete event. Additionally,
      non-verbal linguistic elements (e.g. silence) were frequently employed to
      communicate emotional resonance. DISCUSSION AND CONCLUSIONS: This study is the
      first to systematically catalogue instances of compassionate communication in
      physician-patient dialogues. Further refinement and validation of this
      preliminary taxonomy can guide future education and training interventions to
      facilitate compassion in physician-patient interactions.

PMID- 24305038
TI  - Attraction of Ethiopian phlebotomine sand flies (Diptera: Psychodidae) to light
      and sugar-yeast mixtures (CO(2)).
AB  - BACKGROUND: Visceral leishmaniasis (VL) known as Kala-Azar is a serious systemic
      disease caused by Leishmania donovani parasites (Trypanosomatidae:
      Kinetoplastida). The disease is prevalent in the Indian Sub-continent, East
      Africa and Brazil. In Africa, the worst affected regions are in Sudan, with an
      estimated 15,000-20,000 cases annually and Ethiopia with 5,000-7,000 cases a
      year. The main vector of VL in Sudan and Northern Ethiopia is Phlebotomus
      orientalis, a sand fly frequently found in association with Acacia spp and
      Balanite spp woodlands. METHODS: To optimize sampling of sand flies for
      epidemiological studies in remote areas we tested different means of attraction.
      Miniature suction traps employing 2AA batteries (3 V) were deployed in the up
      draft orientation and baited with chemical light-sticks (Red, Yellow and Green),
      or bakers' yeast in sugar solution (emitting CO2 and perhaps other attractants).
      These traps were compared with standard CDC incandescent light traps employing 6
      V batteries. Trials were conducted during two consecutive years at different
      localities around Sheraro, a town in West Tigray, Northern Ethiopia. RESULTS: The
      sand fly species composition was similar but not identical in the different
      locations tested with different Sergentomyia spp. predominating. Phlebotomus spp.
      comprised less than 1% of the catches during the first year trials (November -
      December 2011) but increased markedly during the second year trials performed
      later in the dry season at the height of the sand fly season in February 2012.
      Although there did not appear to be a species bias towards different light wave
      lengths, fermenting yeast in sugar solution attracted relatively more Phlebotomus
      spp. and Sergentomyia schwetzi. CONCLUSIONS: Although the standard 6 V CDC
      incandescent light traps captured more sand flies, light-weight (~350 g) 3 V
      suction traps baited with chemical light-sticks were shown to be effective means
      of monitoring sand flies. Such traps operated without light and baited with yeast
      in sugar solution caught relatively more Phlebotomus spp.

PMID- 24305040
TI  - Nb, F-codoped TiO2 hollow spheres with high visible light photocatalytic
      activity.
AB  - Nb, F-codoped TiO2 hollow spheres (NFTSs) were successfully synthesized via a
      hydrothermal method with niobium oxide, hydrofluoric acid, and tetrabutyl
      titanate. The obtained spheres were hollow, with a diameter of about 2 MUm, and
      the sphere wall was made up of nanorods arranged close together. The NFTSs
      presented anatase phase with more {001} facets exposed, which could be mainly
      attributed to F ions which were preferentially adsorbed on the {001} facets
      during the crystal growth process. Ti3+ states in NFTSs were increased due to Nb,
      F-codoping, resulting in the decrease of the band gap and the red shift of the
      absorption edge of the NFTSs. The NFTSs exhibited 20.1% higher photocatalytic
      speed compared to P25 on the degradation of methylene orange. 

PMID- 24305039
TI  - Development and psychometric properties of a questionnaire to assess barriers to
      feeding critically ill patients.
AB  - BACKGROUND: To successfully implement the recommendations of critical care
      nutrition guidelines, one potential approach is to identify barriers to providing
      optimal enteral nutrition (EN) in the intensive care unit (ICU), and then address
      these barriers systematically. Therefore, the purpose of this study was to
      develop a questionnaire to assess barriers to enterally feeding critically ill
      patients and to conduct preliminary validity testing of the new instrument.
      METHODS: The content of the questionnaire was guided by a published conceptual
      framework, literature review, and consultation with experts. The questionnaire
      was pre-tested on a convenience sample of 32 critical care practitioners, and
      then field tested with 186 critical care providers working at 5 hospitals in
      North America. The revised questionnaire was pilot tested at another ICU (n =
      43). Finally, the questionnaire was distributed to a random sample of ICU nurses
      twice, two weeks apart, to determine test retest reliability (n = 17).
      Descriptive statistics, exploratory factor analysis, Cronbach alpha, intraclass
      correlations (ICC), and kappa coefficients were conducted to assess validity and
      reliability. RESULTS: We developed a questionnaire with 26 potential barriers to
      delivery of EN asking respondents to rate their importance as barriers in their
      ICU. Face and content validity of the questionnaire was established through
      literature review and expert input. The factor analysis indicated a five-factor
      solution and accounted for 72% of the variance in barriers: guideline
      recommendations and implementation strategies, delivery of EN to the patient,
      critical care provider attitudes and behavior, dietitian support, and ICU
      resources. Overall, the indices of internal reliability for the derived factor
      subscales and the overall instrument were acceptable (subscale Cronbach alphas
      range 0.84 - 0.89). However, the test retest reliability was variable and below
      acceptable thresholds for the majority of items (ICC's range -0.13 to 0.70). The
      within group agreement, an indices reflecting the reliability of aggregating
      individual responses to the ICU level was also variable (ICC's range 0.0 to
      0.82). CONCLUSIONS: We developed a questionnaire to identify barriers to enteral
      feeding in critically ill patients. Additional studies are planned to further
      revise and evaluate the reliability and validity of the instrument.

PMID- 24305041
TI  - Surface code--biophysical signals for apoptotic cell clearance.
AB  - Apoptotic cell death and the clearance of dying cells play an important and
      physiological role in embryonic development and normal tissue turnover. In
      contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is
      orchestrated by the timed release and/or exposure of so-called 'find-me', 'eat
      me' and 'tolerate me' signals. Mononuclear phagocytes are attracted by various
      'find-me' signals, including proteins, nucleotides, and phospholipids released by
      the dying cell, whereas the involvement of granulocytes is prevented via 'stay
      away' signals. The exposure of anionic phospholipids like phosphatidylserine (PS)
      by apoptotic cells on the outer leaflet of the plasma membrane is one of the main
      'eat me' signals. PS is recognized by a number of innate receptors as well as by
      soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes
      are able to discriminate between viable and apoptotic cells both exposing PS. Due
      to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of
      apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not
      only plays an important role in the engulfment process, but also acts as
      'tolerate me' signal inducing the release of anti-inflammatory cytokines by
      phagocytes. An efficient and fast clearance of apoptotic cells is required to
      prevent secondary necrosis and leakage of intracellular danger signals into the
      surrounding tissue. Failure or prolongation of the clearance process leads to the
      release of intracellular antigens into the periphery provoking inflammation and
      development of systemic inflammatory autoimmune disease like systemic lupus
      erythematosus. Here we review the current findings concerning apoptosis-inducing
      pathways, important players of apoptotic cell recognition and clearance as well
      as the role of membrane remodeling in the engulfment of apoptotic cells by
      phagocytes. 

PMID- 24305042
TI  - Human T-lymphotropic virus/HIV co-infection: a clinical review.
AB  - PURPOSE OF REVIEW: Human T-lymphotropic virus (HTLV)/HIV co-infections are often
      undiagnosed, with important clinical implications. The literature is relatively
      sparse with key observations derived in the pre-highly-active antiretroviral
      therapy era. RECENT FINDINGS: The epidemiology of co-infection, the impact of
      each virus on the other, with particular reference to clinical manifestations and
      the impact of antiretroviral therapy on HTLVs are described. SUMMARY: Important
      clinical effects of HTLV/HIV co-infection include the higher rates of myelopathy
      and other neurological disorders and the poor predicative value of CD4+ cell
      counts as a surrogate for immune suppression. Current antiretroviral therapies in
      isolation have no proven effect on HTLV-1/2 proviral load.

PMID- 24305043
TI  - Drug interactions between antiretrovirals and new or emerging direct-acting
      antivirals in HIV/hepatitis C virus coinfection.
AB  - PURPOSE OF REVIEW: We reviewed the pharmacokinetic interactions between direct
      acting antivirals against hepatitis C virus (HCV) and antiretroviral agents.
      RECENT FINDINGS: Most relevant pharmacokinetic studies involve healthy
      individuals and refer to the already licensed HCV protease inhibitors, boceprevir
      and telaprevir. Data from a phase II clinical trial question the clinical
      relevance of the interactions between boceprevir and HIV protease inhibitors. The
      use of a higher dose of telaprevir appears to offset the effect of efavirenz on
      telaprevir metabolism according to another phase II trial. Boceprevir and
      particularly telaprevir substantially increase the exposure to maraviroc,
      similarly to other potent CYP3A4 inhibitors. Different dosages of faldaprevir and
      daclatasvir have been recommended to be used in combination with a boosted HIV
      protease inhibitor vs. an efavirenz-based antiretroviral regimen. HIV protease
      inhibitors appear to substantially increase the exposure to simeprevir. The
      interactions between sofosbuvir and most antiretroviral agents do not appear to
      be of clinical relevance or to require dosage modifications. SUMMARY: The drug
      drug interaction studies for HCV direct-acting antivirals and antiretrovirals are
      important in determining the appropriate drug combinations and dosages. The
      clinical implications of these interactions need further assessment in different
      categories of patients, including those with cirrhosis.

PMID- 24305044
TI  - Globalization means that the relationship.

PMID- 24305045
TI  - Cancer: A suppression switch.

PMID- 24305048
TI  - HMGA2 functions as a competing endogenous RNA to promote lung cancer progression.
AB  - Non-small-cell lung cancer (NSCLC) is the most prevalent histological cancer
      subtype worldwide. As the majority of patients present with invasive, metastatic
      disease, it is vital to understand the basis for lung cancer progression. Hmga2
      is highly expressed in metastatic lung adenocarcinoma, in which it contributes to
      cancer progression and metastasis. Here we show that Hmga2 promotes lung cancer
      progression in mouse and human cells by operating as a competing endogenous RNA
      (ceRNA) for the let-7 microRNA (miRNA) family. Hmga2 can promote the
      transformation of lung cancer cells independent of protein-coding function but
      dependent upon the presence of let-7 sites; this occurs without changes in the
      levels of let-7 isoforms, suggesting that Hmga2 affects let-7 activity by
      altering miRNA targeting. These effects are also observed in vivo, where Hmga2
      ceRNA activity drives lung cancer growth, invasion and dissemination. Integrated
      analysis of miRNA target prediction algorithms and metastatic lung cancer gene
      expression data reveals the TGF-beta co-receptor Tgfbr3 (ref. 12) as a putative
      target of Hmga2 ceRNA function. Tgfbr3 expression is regulated by the Hmga2 ceRNA
      through differential recruitment to Argonaute 2 (Ago2), and TGF-beta signalling
      driven by Tgfbr3 is important for Hmga2 to promote lung cancer progression.
      Finally, analysis of NSCLC-patient gene-expression data reveals that HMGA2 and
      TGFBR3 are coordinately regulated in NSCLC-patient material, a vital corollary to
      ceRNA function. Taken together, these results suggest that Hmga2 promotes lung
      carcinogenesis both as a protein-coding gene and as a non-coding RNA; such dual
      function regulation of gene-expression networks reflects a novel means by which
      oncogenes promote disease progression. 

PMID- 24305049
TI  - p53 status determines the role of autophagy in pancreatic tumour development.
AB  - Macroautophagy (hereafter referred to as autophagy) is a process in which
      organelles termed autophagosomes deliver cytoplasmic constituents to lysosomes
      for degradation. Autophagy has a major role in cellular homeostasis and has been
      implicated in various forms of human disease. The role of autophagy in cancer
      seems to be complex, with reports indicating both pro-tumorigenic and tumour
      suppressive roles. Here we show, in a humanized genetically-modified mouse model
      of pancreatic ductal adenocarcinoma (PDAC), that autophagy's role in tumour
      development is intrinsically connected to the status of the tumour suppressor
      p53. Mice with pancreases containing an activated oncogenic allele of Kras (also
      called Ki-Ras)--the most common mutational event in PDAC--develop a small number
      of pre-cancerous lesions that stochastically develop into PDAC over time.
      However, mice also lacking the essential autophagy genes Atg5 or Atg7 accumulate
      low-grade, pre-malignant pancreatic intraepithelial neoplasia lesions, but
      progression to high-grade pancreatic intraepithelial neoplasias and PDAC is
      blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53,
      loss of autophagy no longer blocks tumour progression, but actually accelerates
      tumour onset, with metabolic analysis revealing enhanced glucose uptake and
      enrichment of anabolic pathways, which can fuel tumour growth. These findings
      provide considerable insight into the role of autophagy in cancer and have
      important implications for autophagy inhibition in cancer therapy. In this
      regard, we also show that treatment of mice with the autophagy inhibitor
      hydroxychloroquine, which is currently being used in several clinical trials,
      significantly accelerates tumour formation in mice containing oncogenic Kras but
      lacking p53.

PMID- 24305050
TI  - Neuroscience: Faster than kiss-and-run.

PMID- 24305051
TI  - A mitochondrial genome sequence of a hominin from Sima de los Huesos.
AB  - Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain
      have unearthed hominin fossils that range in age from the early Pleistocene to
      the Holocene. One of these sites, the 'Sima de los Huesos' ('pit of bones'), has
      yielded the world's largest assemblage of Middle Pleistocene hominin fossils,
      consisting of at least 28 individuals dated to over 300,000 years ago. The
      skeletal remains share a number of morphological features with fossils classified
      as Homo heidelbergensis and also display distinct Neanderthal-derived traits.
      Here we determine an almost complete mitochondrial genome sequence of a hominin
      from Sima de los Huesos and show that it is closely related to the lineage
      leading to mitochondrial genomes of Denisovans, an eastern Eurasian sister group
      to Neanderthals. Our results pave the way for DNA research on hominins from the
      Middle Pleistocene. 

PMID- 24305052
TI  - Modelling the effects of subjective and objective decision making in scientific
      peer review.
AB  - The objective of science is to advance knowledge, primarily in two interlinked
      ways: circulating ideas, and defending or criticizing the ideas of others. Peer
      review acts as the gatekeeper to these mechanisms. Given the increasing concern
      surrounding the reproducibility of much published research, it is critical to
      understand whether peer review is intrinsically susceptible to failure, or
      whether other extrinsic factors are responsible that distort scientists'
      decisions. Here we show that even when scientists are motivated to promote the
      truth, their behaviour may be influenced, and even dominated, by information
      gleaned from their peers' behaviour, rather than by their personal dispositions.
      This phenomenon, known as herding, subjects the scientific community to an
      inherent risk of converging on an incorrect answer and raises the possibility
      that, under certain conditions, science may not be self-correcting. We further
      demonstrate that exercising some subjectivity in reviewer decisions, which serves
      to curb the herding process, can be beneficial for the scientific community in
      processing available information to estimate truth more accurately. By examining
      the impact of different models of reviewer decisions on the dynamic process of
      publication, and thereby on eventual aggregation of knowledge, we provide a new
      perspective on the ongoing discussion of how the peer-review process may be
      improved. 

PMID- 24305053
TI  - Perturbed neural activity disrupts cerebral angiogenesis during a postnatal
      critical period.
AB  - During the neonatal period, activity-dependent neural-circuit remodelling
      coincides with growth and refinement of the cerebral microvasculature. Whether
      neural activity also influences the patterning of the vascular bed is not known.
      Here we show in neonatal mice, that neither reduction of sensory input through
      whisker trimming nor moderately increased activity by environmental enrichment
      affects cortical microvascular development. Unexpectedly, chronic stimulation by
      repetitive sounds, whisker deflection or motor activity led to a near arrest of
      angiogenesis in barrel, auditory and motor cortices, respectively. Chemically
      induced seizures also caused robust reductions in microvascular density. However,
      altering neural activity in adult mice did not affect the vasculature.
      Histological analysis and time-lapse in vivo two-photon microscopy revealed that
      hyperactivity did not lead to cell death or pruning of existing vessels but
      rather to reduced endothelial proliferation and vessel sprouting. This anti
      angiogenic effect was prevented by administration of the nitric oxide synthase
      (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency,
      suggesting that excessive nitric oxide released from hyperactive interneurons and
      glia inhibited vessel growth. Vascular deficits persisted long after cessation of
      hyperstimulation, providing evidence for a critical period after which proper
      microvascular patterning cannot be re-established. Reduced microvascular density
      diminished the ability of the brain to compensate for hypoxic challenges, leading
      to dendritic spine loss in regions distant from capillaries. Therefore, excessive
      sensorimotor stimulation and repetitive neural activation during early childhood
      may cause lifelong deficits in microvascular reserve, which could have important
      consequences for brain development, function and pathology. 

PMID- 24305056
TI  - Nursing in the 21st century: perfect practice, imperfect practitioners.

PMID- 24305054
TI  - Structural mechanism of ligand activation in human GABA(B) receptor.
AB  - Human GABA(B) (gamma-aminobutyric acid class B) receptor is a G-protein-coupled
      receptor central to inhibitory neurotransmission in the brain. It functions as an
      obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the crystal
      structures of a heterodimeric complex between the extracellular domains of GBR1
      and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo and
      antagonist-bound structures represent the resting state of the receptor; the
      agonist-bound complex corresponds to the active state. Both subunits adopt an
      open conformation at rest, and only GBR1 closes on agonist-induced receptor
      activation. The agonists and antagonists are anchored in the interdomain crevice
      of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the
      open conformation of the inactive state, whereas an agonist induces its domain
      closure for activation. Our data reveal a unique activation mechanism for GABA(B)
      receptor that involves the formation of a novel heterodimer interface between
      subunits.

PMID- 24305057
TI  - Current noise in three-terminal hybrid quantum point contacts.
AB  - We investigate the current noise of three-terminal hybrid structures at arbitrary
      bias voltages. Our results indicate that the noise can be a useful tool to
      extract dynamical information in multi-terminal hybrid structures. The zero
      frequency noise is sensitive to the coupling with a normal lead. As a result, the
      characteristic multiple-step structure of the noise Fano factor due to multiple
      Andreev reflection will be suppressed as we increase this coupling. In addition,
      the internal dynamics due to processes of Andreev reflection and multiple Andreev
      reflection raises rich features in the noise spectrum corresponding to the energy
      differences of various dynamical processes. 

PMID- 24305055
TI  - Ultrafast endocytosis at mouse hippocampal synapses.
AB  - To sustain neurotransmission, synaptic vesicles and their associated proteins
      must be recycled locally at synapses. Synaptic vesicles are thought to be
      regenerated approximately 20 s after fusion by the assembly of clathrin scaffolds
      or in approximately 1 s by the reversal of fusion pores via 'kiss-and-run'
      endocytosis. Here we use optogenetics to stimulate cultured hippocampal neurons
      with a single stimulus, rapidly freeze them after fixed intervals and examine the
      ultrastructure using electron microscopy--'flash-and-freeze' electron microscopy.
      Docked vesicles fuse and collapse into the membrane within 30 ms of the stimulus.
      Compensatory endocytosis occurs within 50 to 100 ms at sites flanking the active
      zone. Invagination is blocked by inhibition of actin polymerization, and scission
      is blocked by inhibiting dynamin. Because intact synaptic vesicles are not
      recovered, this form of recycling is not compatible with kiss-and-run
      endocytosis; moreover, it is 200-fold faster than clathrin-mediated endocytosis.
      It is likely that 'ultrafast endocytosis' is specialized to restore the surface
      area of the membrane rapidly.

PMID- 24305059
TI  - Response Inhibition in Tic Disorders: Waiting to Respond Is Harder When ADHD Is
      Present.
AB  - OBJECTIVE: Tic disorders such as Gilles-de-la-Tourette syndrome (TS) are
      associated with difficulties in withholding movements and sometimes inappropriate
      actions. The present study examined whether these disorders lead to a specific
      difficulty in withholding preprogrammed voluntary movements irrespective of
      decisions on whether or not to move. METHOD: Children with TS with or without
      attention-deficit hyperactivity disorder (ADHD) and controls performed a fast
      paced simple reaction time task involving responses to a target in a rapid letter
      stream (9 letters/s, average foreperiod 332 ms) with feedback on response speed.
      RESULTS: The ADHD group showed more premature responses and more variable
      response time than other groups, whether the timing of the target was predictable
      or not. CONCLUSION: The data indicate that in tic disorders, the presence of ADHD
      is associated with difficulties in waiting to initiate preprogrammed movements
      independently of response selection or response timing difficulties.

PMID- 24305060
TI  - A Pilot Trial of Mindfulness Meditation Training for ADHD in Adulthood: Impact on
      Core Symptoms, Executive Functioning, and Emotion Dysregulation.
AB  - OBJECTIVE: Mindfulness meditation training is garnering increasing empirical
      interest as an intervention for ADHD in adulthood, although no studies of
      mindfulness as a standalone treatment have included a sample composed entirely of
      adults with ADHD or a comparison group. The aim of this study was to assess the
      feasibility, acceptability, and preliminary efficacy of mindfulness meditation
      for ADHD, executive functioning (EF), and emotion dysregulation symptoms in an
      adult ADHD sample. METHOD: Adults with ADHD were stratified by ADHD medication
      status and otherwise randomized into an 8-week group-based mindfulness treatment
      ( n = 11) or waitlist group ( n = 9). RESULTS: Treatment feasibility and
      acceptability were positive. In addition, self-reported ADHD and EF symptoms
      (assessed in the laboratory and ecological momentary assessment), clinician
      ratings of ADHD and EF symptoms, and self-reported emotion dysregulation improved
      for the treatment group relative to the waitlist group over time with large
      effect sizes. Improvement was not observed for EF tasks. CONCLUSION: Findings
      support preliminary treatment efficacy, though require larger trials.

PMID- 24305061
TI  - Attenuated dopaminergic tone in the paraventricular nucleus contributing to
      sympathoexcitation in rats with Type 2 diabetes.
AB  - The study was conducted to investigate the role for dopamine in the centrally
      mediated sympathoexcitatory response in rats with Type 2 diabetes (T2D). T2D was
      induced by a combination of high-fat diet (HFD) and low-dose streptozotocin
      (STZ). HFD/STZ treatment for 12-14 wk resulted in significant increase in the
      number of FosB-positive cells in the paraventricular nucleus (PVN) and rostral
      ventrolateral medulla (RVLM). In anesthetized rats, administration of exogenous
      dopamine (dopamine hydrochloride, 20 mM) in the PVN, but not in the RVLM,
      elicited decreases in renal sympathetic nerve activity (RSNA) and mean arterial
      pressure (MAP) in control rats and but not in the T2D rats. Blocking the
      endogenous dopamine with dopamine D1/D5 receptor antagonist SCH39166 (2 mM) in
      the PVN and RVLM, resulted in increases in RSNA, MAP, and heart rate (HR) in both
      control and T2D rats. These responses were significantly attenuated in T2D rats
      compared with control rats (PVN - DeltaRSNA: 21 +/- 10 vs. 44 +/- 2%; DeltaMAP: 7
      +/- 3 vs. 19 +/- 6 mmHg, DeltaHR: 17 +/- 5 vs. 32 +/- 4 bpm, P < 0.05). There
      were no significant increases in response to dopamine D2/D3 receptor antagonist
      raclopride application in the PVN and RVLM of both control and T2D rats.
      Furthermore, there were decreased dopamine D1 receptor and D2 receptor
      expressions in the PVN of T2D rats. Taken together, these data suggest that
      reduced endogenous dopaminergic tone within the PVN may contribute to the
      sympathoexcitation in T2D. 

PMID- 24305062
TI  - Pharmacologically induced hypothermia via TRPV1 channel agonism provides
      neuroprotection following ischemic stroke when initiated 90 min after
      reperfusion.
AB  - Traditional methods of therapeutic hypothermia show promise for neuroprotection
      against cerebral ischemia-reperfusion (I/R), however, with limitations. We
      examined effectiveness and specificity of pharmacological hypothermia (PH) by
      transient receptor potential vanilloid 1 (TRPV1) channel agonism in the treatment
      of focal cerebral I/R. Core temperature (T(core)) was measured after subcutaneous
      infusion of TRPV1 agonist dihydrocapsaicin (DHC) in conscious C57BL/6 WT and
      TRPV1 knockout (KO) mice. Acute measurements of heart rate (HR), mean arterial
      pressure (MAP), and cerebral perfusion were measured before and after DHC
      treatment. Focal cerebral I/R (1 h ischemia + 24 h reperfusion) was induced by
      distal middle cerebral artery occlusion. Hypothermia (>8 h) was initiated 90 min
      after start of reperfusion by DHC infusion (osmotic pump). Neurofunction
      (behavioral testing) and infarct volume (TTC staining) were measured at 24 h. DHC
      (1.25 mg/kg) produced a stable drop in T(core) (33 degrees C) in naive and I/R
      mouse models but not in TRPV1 KO mice. DHC (1.25 mg/kg) had no measurable effect
      on HR and cerebral perfusion but produced a slight transient drop in MAP (<6
      mmHg). In stroke mice, DHC infusion produced hypothermia, decreased infarct
      volume by 87%, and improved neurofunctional score. The hypothermic and
      neuroprotective effects of DHC were absent in TRPV1 KO mice or mice maintained
      normothermic with heat support. PH via TRPV1 agonist appears to be a well
      tolerated and effective method for promoting mild hypothermia in the conscious
      mouse. Furthermore, TRPV1 agonism produces effective hypothermia in I/R mice and
      significantly improves outcome when initiated 90 min after start of reperfusion.

PMID- 24305063
TI  - Effects of varying doses of testosterone on atherogenic markers in healthy
      younger and older men.
AB  - Whether exogenous testosterone is proatherogenic remains controversial. We
      assessed the effects of graded doses of testosterone on serum markers of
      oxidative stress, chemotaxis, adhesion, and inflammation in healthy younger and
      older men. In a double-blind, randomized trial, 121 eugonadal men (n = 61, 18-35
      years of age and n = 60, 60-75 years of age) were randomized to one of five
      groups to receive weekly injections of 25, 50, 125, 300, or 600 mg of
      testosterone enanthate for 20 wk, respectively, along with a long-acting
      gonadotropin-releasing hormone (GnRH) agonist. Energy and protein intakes were
      standardized and no resistance training was allowed. We measured plasma levels of
      the atherogenic biomarkers monocyte chemotactic protein-1 (MCP-1), soluble
      intracellular adhesion molecule-1 (sICAM-1), 8-isoprostane-PGF(2alpha) (8-iso
      PGF(2alpha)), and high-sensitivity C-reactive protein (hs-CRP) before and after
      the intervention. Administration of increasing doses of testosterone led to
      reduction in total 8-iso-PGF(2alpha) in the younger (p-trend(Younger) = 0.01),
      but not older (p-trend(Older) = 0.79) men. No significant linear associations
      were observed between testosterone dose and MCP-1, sICAM-1, or hs-CRP (all p
      trend >0.20). In apparently healthy men, over a wide dose range, testosterone did
      not adversely affect atherogenic biomarkers. Long-term studies with larger sample
      sizes are warranted to determine whether testosterone supplementation affects
      atherosclerosis progression and cardiovascular risk.

PMID- 24305064
TI  - Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.
AB  - Despite the fact that urogenito-sexual complications significantly impact the
      quality of life of diabetic patients, a robust in vivo experimental model is
      lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK)
      rat and responses to standard-of-care treatments for each disorder have been
      assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats
      (n = 23), characterized for their metabolic parameters, were used. Bladder
      function was assessed by cystometry in conscious rats treated by intravenous
      solifenacin (1 mg/kg). Subsequently, erectile function was assessed under
      anesthesia following electrical stimulation of the cavernous nerve in presence of
      intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with
      a significant increase in frequency/amplitude of nonvoiding contractions during
      the filling phase, together with an increase in bladder capacity,
      intercontraction interval, voided volume, and maximal pressure of voiding
      contraction. Solifenacin significantly decreased parameters characterizing
      voiding contractions without modifying voiding efficiency. Erectile function in
      GK rats was markedly impaired and remained so after sildenafil treatment despite
      a significant improvement. GK rats display both bladder and erectile dysfunctions
      and respond at least partially to standard-of-care treatments for each disorder,
      thus representing a suitable model to investigate the pathophysiology and assess
      the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and
      erectile complications. 

PMID- 24305065
TI  - Pyruvate dehydrogenase kinase-4 contributes to the recirculation of gluconeogenic
      precursors during postexercise glycogen recovery.
AB  - During recovery from glycogen-depleting exercise, there is a shift from
      carbohydrate oxidation to glycogen resynthesis. The activity of the pyruvate
      dehydrogenase (PDH) complex may decrease to reduce oxidation of carbohydrates in
      favor of increasing gluconeogenic recycling of carbohydrate-derived substrates
      for this process. The precise mechanism behind this has yet to be elucidated;
      however, research examining mRNA content has suggested that the less-abundant
      pyruvate dehydrogenase kinase-4 (PDK4) may reduce PDH activation during exercise
      recovery. To investigate this, skeletal muscle and liver of wild-type (WT) and
      PDK4-knockout (PDK4-KO) mice were analyzed at rest (Rest), after exercise to
      exhaustion (Exh), and after 2 h of recovery with ad libitum feeding (Rec).
      Although there were no differences in exercise tolerance between genotypes,
      caloric consumption was doubled by PDK4-KO mice during Rec. Because of this, PDK4
      KO mice at Rec supercompensated muscle glycogen to 120% of resting stores.
      Therefore, an extra group of PDK4-KO mice were pair-fed (PF) with WT mice during
      Rec for comparison. PF mice fully replenished muscle glycogen but recovered only
      50% of liver glycogen stores. Concentrations of muscle lactate and alanine were
      also lower in PF than in WT mice, indicating that this decrease may lead to a
      potential reduction of recycled gluconeogenic substrates, due to oxidation of
      their carbohydrate precursors in skeletal muscle, leading to observed reductions
      in hepatic glucose and glycogen concentrations. Because of the impairments seen
      in PF PDK4-KO mice, these results suggest a role for PDK4 in regulating the PDH
      complex in muscle and promoting gluconeogenic precursor recirculation during
      recovery from exhaustive exercise. 

PMID- 24305066
TI  - Altered Tnnt3 characterizes selective weakness of fast fibers in mice
      overexpressing FSHD region gene 1 (FRG1).
AB  - Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is
      characterized by atrophy and weakness of selective muscle groups. FSHD is
      considered an autosomal dominant disease with incomplete penetrance and
      unpredictable variability of clinical expression within families. Mice
      overexpressing FRG1 (FSHD region gene 1), a candidate gene for this disease,
      develop a progressive myopathy with features of the human disorder. Here, we show
      that in FRG1-overexpressing mice, fast muscles, which are the most affected by
      the dystrophic process, display anomalous fast skeletal troponin T (fTnT)
      isoform, resulting from the aberrant splicing of the Tnnt3 mRNA that precedes the
      appearance of dystrophic signs. We determine that muscles of FRG1 mice develop
      less strength due to impaired contractile properties of fast-twitch fibers
      associated with an anomalous MyHC-actin ratio and a reduced sensitivity to
      Ca(2+). We demonstrate that the decrease of Ca(2+) sensitivity of fast-twitch
      fibers depends on the anomalous troponin complex and can be rescued by the
      substitution with the wild-type proteins. Finally, we find that the presence of
      aberrant splicing isoforms of TNNT3 characterizes dystrophic muscles in FSHD
      patients. Collectively, our results suggest that anomalous TNNT3 profile
      correlates with the muscle impairment in both humans and mice. On the basis of
      these results, we propose that aberrant fTnT represents a biological marker of
      muscle phenotype severity and disease progression. 

PMID- 24305067
TI  - PASS-predicted Vitex negundo activity: antioxidant and antiproliferative
      properties on human hepatoma cells--an in vitro study.
AB  - BACKGROUND: Hepatocellular carcinoma is a common type of tumour worldwide with a
      high mortality rate and with low response to current cytotoxic and
      chemotherapeutic drugs. The prediction of activity spectra for the substances
      (PASS) software, which predicted that more than 300 pharmacological effects,
      biological and biochemical mechanisms based on the structural formula of the
      substance was efficiently used in this study to reveal new multitalented actions
      for Vitex negundo (VN) constituents. METHODS: Experimental studies based on
      antioxidant and antiproliferative assays verified the predictions obtained by the
      PASS-predicted design strategy. Antioxidant activity of VN extract was studied
      using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric reducing or antioxidant
      power (FRAP) assays. The antiproliferative activity of VN extract against WRL68
      and HepG2 was investigated based on methylthiazol tetrazolium (MTT)
      spectrophotometric assay. RESULTS: VN extract showed 79.43% inhibition of DPPH
      stable radical with IC50 13.31 +/- 0.18 MUg/ml. This inhibition was too closed to
      butylated hydroxyl toluene (BHT) 82.53% (IC5013.8 +/- 0.14) and gallic acid
      89.51% (IC50 3.1 +/- 0.08). VN extract exhibited the strongest free radical
      scavenging power compared with two commercial antioxidants, BHT and ascorbic
      acid. VN increased the activities of antioxidant enzymes in normal embryonic
      liver cells (WRL68) including, superoxide dismutase (SOD) and glutathione
      peroxidase (GPX) compared with to H2O2 group. The ethanolic extract of VN showed
      cytotoxicity to HepG2 cells in a dose and time-dependent manner with IC50 66.46
      MUg/ml, 57.36 MUg/ml and 65.12 MUg/ml at 24, 48, and 72-hours incubation
      respectively, with no sensitivity in WRL68 cells. This was associated with
      significant elevation in lactate dehydrogenase (LDH) release in HepG2 cells. In
      addition, the activation of caspase-3 enzyme suggesting that the observed
      cytotoxicity was mediated via an intrinsic apoptosis pathway. CONCLUSIONS: PASS
      predicted plant activity could efficiently help in selecting a promising
      pharmaceutical leads with high accuracy and required antioxidant and
      antiproliferative properties. This is the first report on PASS-predicted VN
      activity.

PMID- 24305069
TI  - Editorial Issue 3 2013: a Strategic Framework for Primary Health Care.

PMID- 24305070
TI  - Walking patterns in pregnancy.
AB  - Women are encouraged to be active before, during and after pregnancy. However,
      most pregnant women do not engage in sufficient levels of physical activity. For
      women who experience gestational diabetes mellitus (GDM), physical activity
      recommendations are part of the standard management. Walking is the most common
      activity undertaken by women across the lifespan and often recommended by health
      professionals. Little research specifically exploring the patterns of walking
      before, during and after pregnancy has been undertaken. This study investigated
      patterns of walking undertaken by pregnant women, including those who experienced
      GDM. A sample of convenience was used to recruit pregnant or postpartum women in
      regional New South Wales, Australia. Women completed a self-report physical
      activity survey. The survey also included demographic questions, GDM diagnosis
      and physical activity advice received from health professionals. The respondents
      were divided into two groups; those with GDM (GDM) and those without GDM (NoGDM).
      In both groups, walking declined during pregnancy and returned to prepregnancy
      levels in the postpartum. This decline was similar to the decline observed in
      leisure-time physical activity. The GDM group walked more than the NoGDM group
      and a higher percentage of GDM reported being advised to engage in physical
      activity by health professionals. Even though walking is the most common activity
      undertaken for women across the lifespan, prepregnancy walking levels do not
      necessarily continue during pregnancy. Advice from health professionals may
      assist in maintaining walking levels during pregnancy. Encouraging pregnant women
      to continue their prepregnancy walking level may be a relatively simple strategy
      to increase participation in physical activity. 

PMID- 24305068
TI  - Role of cognitive parameters in dengue hemorrhagic fever and dengue shock
      syndrome.
AB  - Dengue is becoming recognized as one of the most important vector-borne human
      diseases. It is predominant in tropical and subtropical zones but its
      geographical distribution is progressively expanding, making it an escalating
      global health problem of today. Dengue presents with spectrum of clinical
      manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue
      fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life
      threatening illness characterized by plasma leakage due to increased vascular
      permeability. Currently, there are no antiviral modalities or vaccines available
      to treat and prevent dengue. Supportive care with close monitoring is the
      standard clinical practice. The mechanisms leading to DHF/DSS remains poorly
      understood. Multiple factors have been attributed to the pathological mechanism,
      but only a couple of these hypotheses are popular in scientific circles. The
      current discussion focuses on underappreciated factors, temperature, natural IgM,
      and endotoxin, which may be critical components playing roles in dengue
      pathogenesis. 

PMID- 24305073
TI  - Stop the madness.

PMID- 24305074
TI  - Metamorphosis.

PMID- 24305075
TI  - Leadership.

PMID- 24305076
TI  - Implementation of a rib fracture triage protocol in elderly trauma patients.
AB  - Elderly patients are highly susceptible to rib fractures after trauma. The use of
      a clinical pathway to determine resource allocation for patients with rib
      fractures has resulted in positive treatment outcomes. This retrospective study
      assessed the efficacy of a triage protocol involving trauma services on hospital
      length of stay in elderly patients with fractured ribs. Patients who had 3 or
      more ribs fractured experienced a statistically significant reduction in hospital
      length of stay after protocol implementation. We conclude that elderly patients
      with 3 or more rib fractures should be systematically referred to a trauma
      specialist. 

PMID- 24305078
TI  - Implementing a tailored approach for the hand-injured patient: a prospective
      study on the evolution of the posttraumatic psychic distress.
AB  - Mutilating hand injuries are frequently associated with the development of
      psychic impairments such as posttraumatic stress disorder, depression, regression
      of the personality, and refusal of the disease. The psychic distress acts as a
      source of disability that outweighs the functional loss, causing impairments that
      may prevent a full recovery after the accident. The present study highlights the
      need for nurses to be familiar with the emotional response in the patients, to
      implement a specialized and comprehensive approach and detect stress points that
      may require early intervention. 

PMID- 24305079
TI  - Full of sound and fury, signifying nothing: burden of transient noncritical
      monitor alarms in a trauma resuscitation unit.
AB  - We examined the types of patient monitor alarms encountered in the trauma
      resuscitation unit of a major level 1 trauma center. Over a 1-year period, 316688
      alarms were recorded for 6701 trauma patients (47 alarms/patient). Alarms were
      more frequent among patients with a Glasgow Coma Scale of 8 or less. Only 2.4% of
      all alarms were classified as "patient crisis," with the rest in the presumably
      less critical categories "patient advisory," "patient warning," and "system
      warning." Nearly half of alarms were <=5 seconds in duration. In this patient
      population, a 2-second delay would reduce alarms by 25%, and a delay of 5 seconds
      would reduce all alarms by 49%. 

PMID- 24305080
TI  - Sleep behaviors of infants and young children: associated demographic and
      acculturation characteristics among Hispanic teen mothers.
AB  - Accidental suffocation and strangulation in bed is a leading cause of preventable
      infant death. Bed sharing, teen motherhood, and Hispanic ethnicity have been
      associated with infant sleep suffocation death. Fifty-five Hispanic teen mothers
      were surveyed regarding acculturation/demographic characteristics and their
      infants' sleep behaviors. Most participants had 2 foreign-born parents from Latin
      America. Participants with 2 US-born parents were less likely to bed share than
      their less-acculturated peers. Many participants reported not always placing
      their infant in a supine sleep position. There is a significant need to reach out
      to Hispanic teen mothers, particularly from newer immigrant families, with
      culturally and linguistically appropriate multigenerational clinical messaging on
      the risks of infant bed sharing and nonsupine sleep positioning. 

PMID- 24305081
TI  - Rural trauma telemedicine.
AB  - Telemedicine is the ability to provide remote health care to patients with the
      use of a consultant and 2-way interactive technology and telecommunication.
      Traumatic injuries occurring in rural areas frequently carry a greater risk of
      mortality than those same injuries occurring in the urban settings. The purpose
      of this article was to increase practitioner awareness of the potential for
      improved outcomes as a result of the use of telemedicine in rural trauma care.
      The use of trauma telemedicine will help decrease the overall mortality and
      morbidity, length of stay at the urban trauma centers, patient care cost, and
      transfer time. 

PMID- 24305082
TI  - Holistic self-care for rehabilitation experienced by thai buddhist trauma
      patients in areas of political and social unrest.
AB  - This study describes the meaning and practice of holistic self-care for
      rehabilitation among Thai Buddhist trauma patients living in areas of political
      unrest where acts of terrorism occur. Eleven Thai Buddhist trauma patients were
      selected as specified. The data were collected by in-depth interviews between
      November 2011 and April 2012, and analyzed using the Van Manen method.Those
      interviewed described "holistic self-care for rehabilitation" as learning (1) to
      acquire a new life and (2) to bear the increased demands of care as a chronic
      disease. Health care responses fell into 3 categories: (1) improving physical
      self-sufficiency and rehabilitation by increasing muscle strength, pain
      management, and pressure sores; (2) improving psychological well-being by
      applying positive thinking, making an effort to live independently, and following
      a set of religious practices; and (3) finding harmony in life through caution and
      a willingness to adjust one's lifestyle. Although the participants seemed to
      adapt well to their new lifestyles, extensive support from health care
      professionals was necessary. This study promotes better understanding of the
      holistic health care experiences the survivors of trauma have as a result of an
      unstable political situation that includes aspects of social unrest and
      terrorism. 

PMID- 24305084
TI  - In Memoriam: Connie Stalcup Gagliardo: Connie's Legacy.

PMID- 24305085
TI  - Efficacy of immediate patient feedback in emergency psychiatry: a randomized
      controlled trial in a crisis intervention & brief therapy team.
AB  - BACKGROUND: This study looks at the effect of immediate session-by-session
      feedback using short questionnaires for evaluating outcome of and alliance in the
      therapy. Research data strongly suggests that using this feedback informed
      treatment improves the outcome of therapy. However, until now, this method of
      Miller and Duncan has only been examined in clients (generally students) with
      mild problems and in partner counselling. The question addressed by this study is
      whether immediate feedback is also effective when applied during crisis
      intervention and subsequent brief therapy in a psychiatric patient population in
      emergency situations. It also looks at whether 'feedback-informed treatment'
      affects the quality of the alliance. METHOD/DESIGN: To test the hypotheses, all
      patients seeking help from the Crisis Intervention & Brief Therapy Team over a
      two-year period will be followed throughout their treatment up to a maximum of
      six months and a follow-up period of three months after ending the treatment.
      Patients are randomly assigned to two conditions: treatment without feedback and
      treatment with immediate feedback for each session. The therapists all operate in
      both conditions and so they deliver both treatments. An estimated total of 180
      patients, aged 18 years and over, will be included in the study. DISCUSSION: The
      aim of this study is to make clear whether, and to what extent, systematic
      feedback from the patient in this target group during therapy determines the
      course and outcomes of therapy. We also look at whether, and to what extent, the
      quality of the alliance and the motivation of the person delivering treatment
      with respect to the instruments play a role. TRIAL REGISTRATION: NTR3168.

PMID- 24305086
TI  - Adjuvant effects of mannose-binding lectin ligands on the immune response to
      infectious bronchitis vaccine in chickens with high or low serum mannose-binding
      lectin concentrations.
AB  - Mannose-binding lectin (MBL) plays a major role in the immune response as a
      soluble pattern-recognition receptor. MBL deficiency and susceptibility to
      different types of infections have been subject to extensive studies over the
      last decades. In humans and chickens, several studies have shown that MBL
      participates in the protection of hosts against virus infections. Infectious
      bronchitis (IB) is a highly contagious disease of economic importance in the
      poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL
      has earlier been described to play a potential role in the pathogenesis of IBV
      infection and the production of IBV-specific antibodies, which may be exploited
      in optimising IBV vaccine strategies. The present study shows that MBL has the
      capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and
      L10L) selected for high or low MBL serum concentrations, respectively, were
      vaccinated against IBV with or without the addition of the MBL ligands mannan,
      chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV
      vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody
      production in L10H chickens, but not L10L chickens after the second vaccination.
      The addition of FOS to the vaccine also increased the number of circulating CD4+
      cells in L10H chickens compared to L10L chickens. The L10H chickens as well as
      the L10L chickens also showed an increased number of CD4-CD8alpha-gammadelta T
      cells when an MBL ligand was added to the vaccine, most pronouncedly after the
      first vaccination. As MBL ligands co-administered with IBV vaccine induced
      differences between the two chicken lines, these results indirectly suggest that
      MBL is involved in the immune response to IBV vaccination. Furthermore, the
      higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a
      potential adjuvant candidate in an IBV vaccine. 

PMID- 24305087
TI  - Extended-duration new oral anticoagulants for venous thromboprophylaxis in
      patients undergoing total hip arthroplasty: a meta-analysis of the randomized
      controlled trials.

PMID- 24305088
TI  - Neisseria gonorrhoeae and extended-spectrum cephalosporins in California:
      surveillance and molecular detection of mosaic penA.
AB  - BACKGROUND: The spread of Neisseria gonorrhoeae strains with mosaic penA alleles
      and reduced susceptibility to extended-spectrum cephalosporins is a major public
      health problem. While much work has been performed internationally, little is
      known about the genetics or molecular epidemiology of N. gonorrhoeae isolates
      with reduced susceptibility to extended-spectrum cephalosporins in the United
      States. The majority of N. gonorrhoeae infections are diagnosed without a live
      culture. Molecular tools capable of detecting markers of extended-spectrum
      cephalosporin resistance are needed. METHODS: Urethral N. gonorrhoeae isolates
      were collected from 684 men at public health clinics in California in 2011.
      Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime
      and azithromycin were determined by Etest and categorized according to the U.S.
      Centers for Disease Control 2010 alert value breakpoints. 684 isolates were
      screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive
      isolates were subjected to DNA sequencing of their penA alleles and Neisseria
      gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity
      of the screening RTPCR in detecting isolates with alert value extended-spectrum
      cephalosporin MICs, the primers were modified to selectively amplify the mosaic
      XXXIV penA allele. RESULTS: Three mosaic penA alleles were detected including two
      previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the
      29 isolates with an alert value extended-spectrum cephalosporin MIC, all
      possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an
      internationally successful strain associated with multi-drug resistance. The
      modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and
      urine specimens and displayed no amplification of the other penA alleles detected
      in this study. CONCLUSION: N. gonorrhoeae isolates with mosaic penA alleles and
      reduced susceptibility to extended-spectrum cephalosporins are currently
      circulating in California. Isolates with the same NG-MAST ST, penA allele and
      extended-spectrum cephalosporin MICs have caused treatment failures elsewhere.
      The RTPCR assay presented here may be useful for the detection of N. gonorrheoae
      isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs
      in settings where antimicrobial susceptibility testing is unavailable. In an era
      of increasing antimicrobial resistance and decreasing culture capacity, molecular
      assays capable of detecting extended-spectrum cephalosporin of resistance are
      essential to public health.

PMID- 24305090
TI  - [Discovery and clinical application of hepatocyte growth factor].

PMID- 24305089
TI  - Insufficient ER-stress response causes selective mouse cerebellar granule cell
      degeneration resembling that seen in congenital disorders of glycosylation.
AB  - BACKGROUND: Congenital disorders of glycosylation (CDGs) are inherited diseases
      caused by glycosylation defects. Incorrectly glycosylated proteins induce protein
      misfolding and endoplasmic reticulum (ER) stress. The most common form of CDG,
      PMM2-CDG, is caused by deficiency in the cytosolic enzyme phosphomannomutase 2
      (PMM2). Patients with PMM2-CDG exhibit a significantly reduced number of
      cerebellar Purkinje cells and granule cells. The molecular mechanism underlying
      the specific cerebellar neurodegeneration in PMM2-CDG, however, remains elusive.
      RESULTS: Herein, we report that cerebellar granule cells (CGCs) are more
      sensitive to tunicamycin (TM)-induced inhibition of total N-glycan synthesis than
      cortical neurons (CNs). When glycan synthesis was inhibited to a comparable
      degree, CGCs exhibited more cell death than CNs. Furthermore, downregulation of
      PMM2 caused more CGCs to die than CNs. Importantly, we found that upon PMM2
      downregulation or TM treatment, ER-stress response proteins were elevated less
      significantly in CGCs than in CNs, with the GRP78/BiP level showing the most
      significant difference. We further demonstrate that overexpression of GRP78/BiP
      rescues the death of CGCs resulting from either TM-treatment or PMM2
      downregulation. CONCLUSIONS: Our results indicate that the selective
      susceptibility of cerebellar neurons to N-glycosylation defects is due to these
      neurons' inefficient response to ER stress, providing important insight into the
      mechanisms of selective neurodegeneration observed in CDG patients.

PMID- 24305091
TI  - [The molecular mechanism in tumorigenesis and development of pancreatic cancer].

PMID- 24305092
TI  - [Recent advances in the early diagnosis of pancreatic cancer].

PMID- 24305093
TI  - [Current status and future directions of chemotherapy for pancreatic cancer].

PMID- 24305094
TI  - [Current status and prospect of the surgical treatment for pancreatic cancer].

PMID- 24305095
TI  - [Current status and future of the radiotherapy for pancreas cancer].

PMID- 24305096
TI  - [Long-term outcomes of ileal pouch-anal canal anastomosis in children with
      ulcerative colitis].
AB  - The present study investigated the long-term outcomes of restorative
      proctocolectomy in pediatric patients with ulcerative colitis (UC). We report a
      series of 25 patients who underwent total proctocolectomy with ileal pouch-anal
      canal anastomosis (IACA). Surgery was performed for medically intractable colitis
      and severe colitis in 14 and 11 patients, respectively. Early and late
      complications were observed in 6 (24%) and 14 (56%) patients, respectively. The
      long-term quality of life outcomes were satisfactory, including both bowel
      function and social function. Growth retardation was observed in 6 patients. Five
      patients exhibited catch-up growth and 3 patients overcame growth retardation.
      Patients with growth retardation tended to have a younger onset and longer
      duration of UC, as well as a longer duration and higher total dose of steroid
      use. In conclusion, the long-term outcomes of pediatric patients with UC
      undergoing IACA are satisfactory. Furthermore, to minimize the risk of growth
      retardation, surgery should be performed without delay. 

PMID- 24305097
TI  - [A case of duplication of the transverse colon in adult, lined with ciliated
      columnar and squamous epithelium].
AB  - We report a rare case of duplication of the transverse colon in an adult. A 26
      year-old male presented to our hospital with upper left abdominal pain and fever.
      An abdominal computed tomography scan revealed an inflammatory mass in the
      gastrocolic ligament. Although conservative management with fasting and
      antibiotics ameliorated the abdominal pain, the mass remained approximately 5cm
      at its largest diameter. Further investigation with a Gastrografin((r)) enema
      revealed a fistula in the central part of the transverse colon. A perforation of
      the transverse colon was intraoperatively detected; therefore, both the intra
      abdominal abscess and part of the transverse colon were excised. Pathological
      examination revealed duplication of the transverse colon that was lined with
      ciliated columnar epithelium, squamous epithelium, and heterotopic glands. 

PMID- 24305098
TI  - [A case of colonic mucosa-associated lymphoid tissue lymphoma observed under
      endoscopy with narrow-band imaging].
AB  - A 79-year-old man presented with constipation and anal bleeding. Colonoscopy
      revealed a reddish submucosal tumor of the transverse colon that was 20mm in
      diameter. Magnified endoscopy with narrow-band imaging (NBI) of the tumor surface
      revealed a type I pit pattern with decreased density and dilated tree-like
      microvessels. Furthermore, endoscopic ultrasonography showed that the tumor was
      limited to the submucosa. A biopsy was subsequently performed, which suggested
      mucosa-associated lymphoid tissue (MALT) lymphoma. This diagnosis was confirmed
      by endoscopic submucosal dissection (ESD). To the best of our knowledge, this is
      the first case report in which magnified endoscopy with NBI was successfully used
      to diagnose a MALT lymphoma of the colon. In addition, this case report
      demonstrates the utility of ESD for the therapeutic diagnosis of relatively large
      lesions with evidence of invasion limited to the submucosa. 

PMID- 24305099
TI  - [A case report of jackhammer esophagus].
AB  - A 39-year-old female patient was referred to our hospital with a suspected
      esophageal motility disorder following a 4-month history of hiccup and dysphagia.
      Her past medical and family histories were unremarkable. Prior investigation with
      upper gastrointestinal endoscopy and esophagography failed to demonstrate any
      obvious pathology. Therefore, high-resolution manometry was performed, which
      showed the following: an integrated relaxation pressure (IRP) of 11.5mmHg; a
      distal contractile integral (DCI) of 6543mmHg-s-cm; and, a highest DCI of
      9289mmHg-s-cm. A diagnosis of jackhammer esophagus was, therefore, considered. We
      reported on the details of this case and reviewed the relevant literature. 

PMID- 24305100
TI  - [Two cases of distal duodenal gastrointestinal stromal tumor diagnosed by
      endoscopic ultrasound-guided fine-needle aspiration biopsy].
AB  - Gastrointestinal stromal tumor (GIST) of the duodenum is rare. Obtaining tissue
      samples of GIST in the duodenum is difficult, especially when the tumor is
      located in the distal duodenum. Thus, preoperative pathological diagnosis often
      becomes difficult. We performed endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) biopsy for two cases with submucosal tumors in the third
      portion of the duodenum. Tissue samples were successfully obtained and diagnosed
      as GIST. Partial duodenectomy was performed in the two patients. Thus, we believe
      that EUS-FNA is a potentially useful diagnostic aid for submucosal tumors in the
      third portion of the duodenum, and it should be attempted before more invasive
      approaches. 

PMID- 24305101
TI  - [A case of portal hypertension after 5-fluorouracil, leucovorin, and oxaliplatin
      (mFOLFOX6) chemotherapy].
AB  - A 46-year-old man with cancer of the sigmoid colon with hepatic metastasis
      underwent sigmoidectomy, partial hepatectomy, and cholecystectomy in May 2008. He
      subsequently received 10 cycles of a modified 5-fluorouracil, leucovorin, and
      oxaliplatin (mFOLFOX6) regimen as adjuvant chemotherapy from June 2008 to
      December 2008, following which he developed thrombocytopenia and splenomegaly. In
      May 2011, upper gastrointestinal endoscopy was performed, which revealed
      esophageal and gastric varices. The varices were treated endoscopically with
      ligation and balloon-occluded retrograde transvenous obliteration. A liver biopsy
      was performed to determine the cause of the portal hypertension in the absence of
      severe hepatic dysfunction or liver cirrhosis. The biopsy revealed obliteration
      of the peripheral portal veins with sinusoidal dilatation without fibrosis or
      inflammatory cell infiltration in the hepatic lobules. Oxaliplatin-based
      chemotherapy has been associated with hepatovascular injury, such as sinusoidal
      dilatation and fibrosis, resulting in non-cirrhotic portal hypertension as seen
      in this case. 

PMID- 24305102
TI  - [Hemobilia into a metallic biliary stent due to pseudoaneurysm: a case report].
AB  - A 48-year-old man with locally advanced pancreatic cancer underwent combined
      treatment with gemcitabine and proton radiation therapy. Because of subsequent
      obstruction of the common bile duct, a metallic biliary stent was placed and he
      received further gemcitabine chemotherapy. During chemotherapy, he developed an
      acute abdomen with a sudden-onset of tarry stool and jaundice. Gastroduodenoscopy
      revealed hemobilia from the biliary metallic stent. Contrast-enhanced abdominal
      computed tomography revealed the presence of a pseudoaneurysm arising from the
      right hepatic artery adjacent to the top of the stent. Hemostasis of the right
      hepatic artery pseudoaneurysm was achieved via transcatheter arterial
      embolization using cyanoacrylate. 

PMID- 24305103
TI  - [Different clinical courses in two cases of ruptured liver abscesses depending on
      the presence or absence of gas-producing pathogens].
AB  - We report two cases of ruptured pyogenic liver abscesses where one patient
      survived and the other died. We suspected that infection with gas-producing
      bacteria was the cause of the latter outcome, and we reviewed 47 case reports of
      ruptured pyogenic liver abscesses. Of the 47 cases, we determined that 77.6%
      included gas-producing pathogens. Moreover, the presence of gas-producing
      pathogens was associated with a mortality of 22.2%, whereas there were no deaths
      in cases with no gas-producing pathogens. 

PMID- 24305108
TI  - A systematic review of gender-specific rates of unipolar and bipolar disorders in
      community studies of pre-pubertal children.
AB  - OBJECTIVES: Gender-specific rates of unipolar and bipolar disorders are well
      established for cases with post-pubertal onset. However, there is less certainty
      about these rates in pre-pubertal children. We undertook a systematic review of
      community studies that report gender-specific rates for unipolar and bipolar
      disorders in young children, particularly cases of major depression and mania.
      METHOD: Computer databases (Medline, EMBASE, Index to Theses, and PsychInfo) were
      searched for non-clinical observational studies using recognized diagnostic
      criteria to identify unipolar and bipolar disorders in children aged <= 12 years.
      A meta-analysis was undertaken to calculate pooled odds ratios (ORs) for caseness
      for major depression by gender. The limited data on bipolar disorder were
      summarized. RESULTS: Analysis of 12 studies (>15,000 children), indicated that
      the community prevalence of unipolar disorders was higher in boys (1.3%) than in
      girls (0.8%). Rates of major depression were low (0.61%), but boys were
      significantly more likely to meet diagnostic criteria than girls (OR = 1.61; 95%
      confidence interval: 1.11-2.35). Five studies, assessing >5,000 children,
      identified only one case with a probable diagnosis of mania. CONCLUSIONS: This
      systematic review suggests that boys aged <= 12 years are significantly more
      likely to experience major depression than girls. However, in younger children,
      community rates of major depression are low, and it is frequently suggested (but
      not proven) that most cases are comorbid. The absence of mania suggests either
      that childhood bipolar phenotypes do not resemble post-pubertal onset cases or
      that there are problems of case ascertainment.

PMID- 24305110
TI  - Impregnated central venous catheters should be readily used to reduce risk of
      bloodstream infection.

PMID- 24305109
TI  - Comparison of dose calculations between pencil-beam and Monte Carlo algorithms of
      the iPlan RT in arc therapy using a homogenous phantom with 3DVH software.
AB  - BACKGROUND: To create an arc therapy plan, certain current general calculation
      algorithms such as pencil-beam calculation (PBC) are based on discretizing the
      continuous arc into multiple fields to simulate an arc. The iPlan RTTM treatment
      planning system incorporates not only a PBC algorithm, but also a more recent
      Monte Carlo calculation (MCC) algorithm that does not need beam discretization.
      The objective of this study is to evaluate the dose differences in a homogenous
      phantom between PBC and MCC by using a three-dimensional (3D) diode array
      detector (ArcCHECKTM) and 3DVH software. METHODS: A cylindrically shaped 'target'
      region of interest (ROI) and a 'periphery ROI' surrounding the target were
      designed. An arc therapy plan was created to deliver 600 cGy to the target within
      a 350 degrees  rotation angle, calculated using the PBC and MCC algorithms. The
      radiation doses were measured by the ArcCHECK, and reproduced by the 3DVH
      software. Through this process, we could compare the accuracy of both algorithms
      with regard to the 3D gamma passing rate (for the entire area and for each ROI).
      RESULTS: Comparing the PBC and MCC planned dose distributions directly, the 3D
      gamma passing rates for the entire area were 97.7% with the gamma 3%/3 mm
      criterion. Comparing the planned dose to the measured dose, the 3D gamma passing
      rates were 98.8% under the PBC algorithm and 100% under the MCC algorithm. The
      difference was statistically significant (p = 0.034). Furthermore the gamma
      passing rate decreases 7.5% in the PBC when using the 2%/2 mm criterion compared
      to only a 0.4% decrease under the MCC. Each ROI as well as the entire area showed
      statistically significant higher gamma passing rates under the MCC algorithm. The
      failure points that did not satisfy the gamma criteria showed a regular pattern
      repeated every 10 degrees . CONCLUSIONS: MCC showed better accuracy than the PBC
      of the iPlan RT in calculating the dose distribution in arc therapy, which was
      validated with the ArcCHECK and the 3DVH software. This may suggest that the arc
      step of 10 degrees  is too large in the PBC algorithm in the iPlan RT.

PMID- 24305111
TI  - Variation and linkage disequilibrium between a structurally polymorphic Alu
      located near the OR12D2 gene of the extended major histocompatibility complex
      class I region and HLA-A alleles.
AB  - We investigated the genetic structure and population frequency of an Alu repeat
      dimorphism (absence or presence) located near the OR12D2 gene within the
      olfactory receptor gene region telomeric of the alpha HLA class I region (HLA-J, 
      A, -G, -F). The structurally polymorphic Alu insertion (POALIN) locus rs33972478
      that we designated as AluOR and its allele and haplotype frequencies and
      association with HLA-A and six other structurally polymorphic retroelements (3
      Alu, 2 SVA and an HERVK9) were determined in 100 Japanese, 174 Caucasians and 100
      African American DNA samples. The AluOR insertion varied in population frequency
      between 14.4% and 31.5% with significant differences between the Japanese and
      Caucasians, but not between the Caucasian and African Americans. Although AluOR
      is located 600 kb from the HLA-A gene, there was a significant linkage
      disequilibrium between the two loci and a high percentage association of the
      AluOR insertion with HLA-A29 (79%) in Caucasians and HLA-A31 (69.4%) in Japanese.
      Inferred haplotypes among three-locus to eight-locus haplotype structures showed
      maximum differences between the populations with the eight-locus haplotypes. The
      most frequent multilocus haplotype shared between the populations was the HLA-A2
      allele in combination with the AluHG insertion. The AluOR whether investigated
      alone or together with the HLA class I alleles and other dimorphic retroelements
      is an informative ancestral marker for the identification of lineages and
      variations within the same and/or different populations and for examining the
      linkage and crossing-over between the HLA and OR genomic regions in the extended
      MHC.

PMID- 24305114
TI  - Risjord's philosophy of nursing science: concerns and questions.

PMID- 24305115
TI  - Microrheology of keratin networks in cancer cells.
AB  - Microrheology is a valuable tool to determine viscoelastic properties of polymer
      networks. For this purpose measurements with embedded tracer beads inside the
      extracted network of pancreatic cancer cells were performed. Observing the beads
      motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The
      complex shear modulus is divided into real and imaginary parts which give insight
      into the mechanical properties of the cell. The dependency on the distance of the
      embedded beads to the rim of the nucleus shows a tendency for a decreasing
      storage modulus. We draw conclusions on the network topology of the keratin
      network types based on the mechanical behavior.

PMID- 24305113
TI  - Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial
      extracts.
AB  - BACKGROUND: Marine microorganisms are considered to be an important source of
      bioactive molecules against various diseases and have great potential to increase
      the number of lead molecules in clinical trials. Progress in novel microbial
      culturing techniques as well as greater accessibility to unique oceanic habitats
      has placed the marine environment as a new frontier in the field of natural
      product drug discovery. METHODS: A total of 24 microbial extracts from deep-sea
      brine pools in the Red Sea have been evaluated for their anticancer potential
      against three human cancer cell lines. Downstream analysis of these six most
      potent extracts was done using various biological assays, such as Caspase-3/7
      activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression
      of gammaH2Ax, Caspase-8 and -9 using western blotting. RESULTS: In general, most
      of the microbial extracts were found to be cytotoxic against one or more cancer
      cell lines with cell line specific activities. Out of the 13 most active
      microbial extracts, six extracts were able to induce significantly higher
      apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts
      from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of
      events of apoptotic pathway involving MMP disruption, caspase-3/7 activity,
      caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas
      another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated
      apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter
      israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any
      change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent
      apoptosis induction. However, further detection of a PARP-1 cleavage product, and
      the observed changes in caspase-8 and -9 suggested the involvement of caspase
      mediated apoptotic pathways. CONCLUSION: Altogether, the study offers novel
      findings regarding the anticancer potential of several halophilic bacterial
      species inhabiting the Red Sea (at the depth of 1500-2500 m), which constitute
      valuable candidates for further isolation and characterization of bioactive
      molecules.

PMID- 24305116
TI  - Comparison of resistive switching characteristics using copper and aluminum
      electrodes on GeOx/W cross-point memories.
AB  - Comparison of resistive switching memory characteristics using copper (Cu) and
      aluminum (Al) electrodes on GeOx/W cross-points has been reported under low
      current compliances (CCs) of 1 nA to 50 MUA. The cross-point memory devices are
      observed by high-resolution transmission electron microscopy (HRTEM). Improved
      memory characteristics are observed for the Cu/GeOx/W structures as compared to
      the Al/GeOx/W cross-points owing to AlOx formation at the Al/GeOx interface. The
      RESET current increases with the increase of the CCs varying from 1 nA to 50 MUA
      for the Cu electrode devices, while the RESET current is high (>1 mA) and
      independent of CCs varying from 1 nA to 500 MUA for the Al electrode devices. An
      extra formation voltage is needed for the Al/GeOx/W devices, while a low
      operation voltage of +/-2 V is needed for the Cu/GeOx/W cross-point devices.
      Repeatable bipolar resistive switching characteristics of the Cu/GeOx/W cross
      point memory devices are observed with CC varying from 1 nA to 50 MUA, and
      unipolar resistive switching is observed with CC >100 MUA. High resistance ratios
      of 102 to 104 for the bipolar mode (CCs of 1 nA to 50 MUA) and approximately 108
      for the unipolar mode are obtained for the Cu/GeOx/W cross-points. In addition,
      repeatable switching cycles and data retention of 103 s are observed under a low
      current of 1 nA for future low-power, high-density, nonvolatile, nanoscale memory
      applications. 

PMID- 24305117
TI  - How sexual harassment changed the way I work.

PMID- 24305129
TI  - Iran hit by drug shortage.

PMID- 24305130
TI  - Hominin DNA baffles experts.

PMID- 24305131
TI  - Image search triggers Italian police probe.

PMID- 24305132
TI  - Bacteria evade detection net.

PMID- 24305133
TI  - Museums hunt for relics from genomics' early days.

PMID- 24305135
TI  - Global health: One million deaths.

PMID- 24305137
TI  - In retrospect: The Feynman Lectures on Physics.

PMID- 24305136
TI  - Geology: North America's broken heart.

PMID- 24305139
TI  - Sustainable management: Recycle waste for nourishing soils.

PMID- 24305140
TI  - Climate science: Take more care over glacier facts.

PMID- 24305141
TI  - Research: All journals need to correct errors.

PMID- 24305142
TI  - Fifty years: Doctor Who and the ageing enigma.

PMID- 24305143
TI  - Gut microbiota: Please pass the microbes.

PMID- 24305144
TI  - Leonard Herzenberg (1931-2013).

PMID- 24305145
TI  - Coastal regions.

PMID- 24305146
TI  - North Atlantic warming and the retreat of Greenland's outlet glaciers.
AB  - Mass loss from the Greenland ice sheet quadrupled over the past two decades,
      contributing a quarter of the observed global sea-level rise. Increased submarine
      melting is thought to have triggered the retreat of Greenland's outlet glaciers,
      which is partly responsible for the ice loss. However, the chain of events and
      physical processes remain elusive. Recent evidence suggests that an anomalous
      inflow of subtropical waters driven by atmospheric changes, multidecadal natural
      ocean variability and a long-term increase in the North Atlantic's upper ocean
      heat content since the 1950s all contributed to a warming of the subpolar North
      Atlantic. This led, in conjunction with increased runoff, to enhanced submarine
      glacier melting. Future climate projections raise the potential for continued
      increases in warming and ice-mass loss, with implications for sea level and
      climate. 

PMID- 24305147
TI  - Coastal flooding by tropical cyclones and sea-level rise.
AB  - The future impacts of climate change on landfalling tropical cyclones are
      unclear. Regardless of this uncertainty, flooding by tropical cyclones will
      increase as a result of accelerated sea-level rise. Under similar rates of rapid
      sea-level rise during the early Holocene epoch most low-lying sedimentary
      coastlines were generally much less resilient to storm impacts. Society must
      learn to live with a rapidly evolving shoreline that is increasingly prone to
      flooding from tropical cyclones. These impacts can be mitigated partly with
      adaptive strategies, which include careful stewardship of sediments and
      reductions in human-induced land subsidence. 

PMID- 24305148
TI  - Tidal wetland stability in the face of human impacts and sea-level rise.
AB  - Coastal populations and wetlands have been intertwined for centuries, whereby
      humans both influence and depend on the extensive ecosystem services that
      wetlands provide. Although coastal wetlands have long been considered vulnerable
      to sea-level rise, recent work has identified fascinating feedbacks between plant
      growth and geomorphology that allow wetlands to actively resist the deleterious
      effects of sea-level rise. Humans alter the strength of these feedbacks by
      changing the climate, nutrient inputs, sediment delivery and subsidence rates.
      Whether wetlands continue to survive sea-level rise depends largely on how human
      impacts interact with rapid sea-level rise, and socio-economic factors that
      influence transgression into adjacent uplands. 

PMID- 24305149
TI  - The changing carbon cycle of the coastal ocean.
AB  - The carbon cycle of the coastal ocean is a dynamic component of the global carbon
      budget. But the diverse sources and sinks of carbon and their complex
      interactions in these waters remain poorly understood. Here we discuss the
      sources, exchanges and fates of carbon in the coastal ocean and how anthropogenic
      activities have altered the carbon cycle. Recent evidence suggests that the
      coastal ocean may have become a net sink for atmospheric carbon dioxide during
      post-industrial times. Continued human pressures in coastal zones will probably
      have an important impact on the future evolution of the coastal ocean's carbon
      budget. 

PMID- 24305150
TI  - Offshore fresh groundwater reserves as a global phenomenon.
AB  - The flow of terrestrial groundwater to the sea is an important natural component
      of the hydrological cycle. This process, however, does not explain the large
      volumes of low-salinity groundwater that are found below continental shelves.
      There is mounting evidence for the global occurrence of offshore fresh and
      brackish groundwater reserves. The potential use of these non-renewable reserves
      as a freshwater resource provides a clear incentive for future research. But the
      scope for continental shelf hydrogeology is broader and we envisage that it can
      contribute to the advancement of other scientific disciplines, in particular
      sedimentology and marine geochemistry. 

PMID- 24305151
TI  - Ecosystem-based coastal defence in the face of global change.
AB  - The risk of flood disasters is increasing for many coastal societies owing to
      global and regional changes in climate conditions, sea-level rise, land
      subsidence and sediment supply. At the same time, in many locations, conventional
      coastal engineering solutions such as sea walls are increasingly challenged by
      these changes and their maintenance may become unsustainable. We argue that flood
      protection by ecosystem creation and restoration can provide a more sustainable,
      cost-effective and ecologically sound alternative to conventional coastal
      engineering and that, in suitable locations, it should be implemented globally
      and on a large scale. 

PMID- 24305152
TI  - Green and golden seaweed tides on the rise.
AB  - Sudden beaching of huge seaweed masses smother the coastline and form rotting
      piles on the shore. The number of reports of these events in previously
      unaffected areas has increased worldwide in recent years. These 'seaweed tides'
      can harm tourism-based economies, smother aquaculture operations or disrupt
      traditional artisanal fisheries. Coastal eutrophication is the obvious, ultimate
      explanation for the increase in seaweed biomass, but the proximate processes that
      are responsible for individual beaching events are complex and require dedicated
      study to develop effective mitigation strategies. Harvesting the macroalgae, a
      valuable raw material, before they beach could well be developed into an
      effective solution. 

PMID- 24305153
TI  - Planetary science: Shadows cast on Moon's origin.

PMID- 24305154
TI  - Astrophysics: Magnetic fields in gamma-ray bursts.

PMID- 24305155
TI  - Structural biology: Ion channel seen by electron microscopy.

PMID- 24305156
TI  - Nobel 2013 Chemistry: Methods for computational chemistry.

PMID- 24305157
TI  - Nobel 2013 Economics: Predicting asset prices.

PMID- 24305159
TI  - Nobel 2013 Physics: Endowing particles with mass.

PMID- 24305158
TI  - Nobel 2013 Physiology or medicine: Traffic control system within cells.

PMID- 24305160
TI  - Structure of the TRPV1 ion channel determined by electron cryo-microscopy.
AB  - Transient receptor potential (TRP) channels are sensors for a wide range of
      cellular and environmental signals, but elucidating how these channels respond to
      physical and chemical stimuli has been hampered by a lack of detailed structural
      information. Here we exploit advances in electron cryo-microscopy to determine
      the structure of a mammalian TRP channel, TRPV1, at 3.4 A resolution, breaking
      the side-chain resolution barrier for membrane proteins without crystallization.
      Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central
      ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore
      loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide
      extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain'
      interacts with the S4-S5 linker, consistent with its contribution to allosteric
      modulation. Subunit organization is facilitated by interactions among cytoplasmic
      domains, including amino-terminal ankyrin repeats. These observations provide a
      structural blueprint for understanding unique aspects of TRP channel function. 

PMID- 24305162
TI  - Highly polarized light from stable ordered magnetic fields in GRB 120308A.
AB  - After the initial burst of gamma-rays that defines a gamma-ray burst (GRB),
      expanding ejecta collide with the circumburst medium and begin to decelerate at
      the onset of the afterglow, during which a forward shock travels outwards and a
      reverse shock propagates backwards into the oncoming collimated flow, or 'jet'.
      Light from the reverse shock should be highly polarized if the jet's magnetic
      field is globally ordered and advected from the central engine, with a position
      angle that is predicted to remain stable in magnetized baryonic jet models or
      vary randomly with time if the field is produced locally by plasma or
      magnetohydrodynamic instabilities. Degrees of linear polarization of P ~ 10 per
      cent in the optical band have previously been detected in the early afterglow,
      but the lack of temporal measurements prevented definitive tests of competing jet
      models. Hours to days after the gamma-ray burst, polarization levels are low (P <
      4 per cent), when emission from the shocked ambient medium dominates. Here we
      report the detection of P =28(+4)(-4) per cent in the immediate afterglow of
      Swift gamma-ray burst GRB 120308A, four minutes after its discovery in the gamma
      ray band, decreasing to P = 16(+5)(-4) per cent over the subsequent ten minutes.
      The polarization position angle remains stable, changing by no more than 15
      degrees over this time, with a possible trend suggesting gradual rotation and
      ruling out plasma or magnetohydrodynamic instabilities. Instead, the polarization
      properties show that GRBs contain magnetized baryonic jets with large-scale
      uniform fields that can survive long after the initial explosion.

PMID- 24305161
TI  - TRPV1 structures in distinct conformations reveal activation mechanisms.
AB  - Transient receptor potential (TRP) channels are polymodal signal detectors that
      respond to a wide range of physical and chemical stimuli. Elucidating how these
      channels integrate and convert physiological signals into channel opening is
      essential to understanding how they regulate cell excitability under normal and
      pathophysiological conditions. Here we exploit pharmacological probes (a peptide
      toxin and small vanilloid agonists) to determine structures of two activated
      states of the capsaicin receptor, TRPV1. A domain (consisting of transmembrane
      segments 1-4) that moves during activation of voltage-gated channels remains
      stationary in TRPV1, highlighting differences in gating mechanisms for these
      structurally related channel superfamilies. TRPV1 opening is associated with
      major structural rearrangements in the outer pore, including the pore helix and
      selectivity filter, as well as pronounced dilation of a hydrophobic constriction
      at the lower gate, suggesting a dual gating mechanism. Allosteric coupling
      between upper and lower gates may account for rich physiological modulation
      exhibited by TRPV1 and other TRP channels. 

PMID- 24305163
TI  - Foundering of lower island-arc crust as an explanation for the origin of the
      continental Moho.
AB  - A long-standing theory for the genesis of continental crust is that it is formed
      in subduction zones. However, the observed seismic properties of lower crust and
      upper mantle in oceanic island arcs differ significantly from those in the
      continental crust. Accordingly, significant modifications of lower arc crust must
      occur, if continental crust is indeed formed from island arcs. Here we
      investigate how the seismic characteristics of arc crust are transformed into
      those of the continental crust by calculating the density and seismic structure
      of two exposed sections of island arc (Kohistan and Talkeetna). The Kohistan
      crustal section is negatively buoyant with respect to the underlying depleted
      upper mantle at depths exceeding 40 kilometres and is characterized by a steady
      increase in seismic velocity similar to that observed in active arcs. In
      contrast, the lower Talkeetna crust is density sorted, preserving only relicts
      (about ten to a hundred metres thick) of rock with density exceeding that of the
      underlying mantle. Specifically, the foundering of the lower Talkeetna crust
      resulted in the replacement of dense mafic and ultramafic cumulates by residual
      upper mantle, producing a sharp seismic discontinuity at depths of around 38 to
      42 kilometres, characteristic of the continental Mohorovicic discontinuity (the
      Moho). Dynamic calculations indicate that foundering is an episodic process that
      occurs in most arcs with a periodicity of half a million to five million years.
      Moreover, because foundering will continue after arc magmatism ceases, this
      process ultimately results in the formation of the continental Moho. 

PMID- 24305165
TI  - Human ribosomal protein L9 is a Bax suppressor that promotes cell survival in
      yeast.
AB  - The identification of a human ribosomal protein L9 (hRPL9) cDNA as a sequence
      capable of suppressing the lethal effects of heterologously expressed murine Bax
      in yeast led us to investigate its antiapoptotic potential. Using growth and
      viability assays, we show that yeast cells heterologously expressing hRPL9 are
      resistant to the growth inhibitory and lethal effects of exogenously supplied
      copper, indicating that it has pro-survival properties. To explore potential
      mechanisms, we used yeast mutants defective in all three types of programmed cell
      death (apoptosis, necrosis, and autophagy). The ability to retain pro-survival
      function in all the mutants suggests that hRPL9 may regulate a common pro-death
      process. In contrast, the yeast RPL9 orthologues, RPL9A and RPL9B, have opposite
      effects when overexpressed in yeast. In effect, instead of showing resistance to
      stress, RPL9A and RPL9B overexpressing cells show reduced cell growth. Further
      analysis indicates that the effects of overexpressed RPL9A and RPL9B are not in
      themselves lethal, instead, they serve to increase cell doubling time. Thus,
      yeast RPL9s are more representative of RPs whose extra-ribosomal function is
      similar to that of tumor suppressors. Taken together, our results demonstrate
      that RPL9 represents a species- and sequence-specific regulator of cell growth
      and survival. 

PMID- 24305166
TI  - Determinants of the creatinine clearance to glomerular filtration rate ratio in
      patients with chronic kidney disease: a cross-sectional study.
AB  - BACKGROUND: Creatinine secretion, as quantified by the ratio of creatinine
      clearance (CrCl) to glomerular filtration rate (GFR), may introduce another
      source of error when using serum creatinine concentration to estimate GFR. Few
      studies have examined determinants of the CrCl/GFR ratio. We sought to study
      whether higher levels of albuminuria would be associated with higher, and being
      non-Hispanic black with lower, CrCl/GFR ratio. METHODS: We did a cross-sectional
      analysis of 1342 patients with chronic kidney disease from the Chronic Renal
      Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR)
      and 24-hour urine collections. Our predictors included urine albumin as
      determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999
      and >=3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black,
      Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion.
      RESULTS: Mean iGFR was 48.0 +/- 19.9 mL/min/1.73 m2, median albuminuria was 84 mg
      per day, and 36.8% of the study participants were non-Hispanic black. Mean
      CrCl/iGFR ratio was 1.19 +/- 0.48. There was no association between the CrCl/iGFR
      ratio and urine albumin (coefficient 0.11 [95% CI-0.01-0.22] for higest verus
      lowest levels of albuminuria, p = 0.07). Also, there was no association between
      race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was-0.03
      [95% CI-0.09-0.03] compared with whites, p = 0.38). CONCLUSIONS: Contrary to what
      had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with
      degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than
      reported by several frequently cited reports in the literature.

PMID- 24305168
TI  - Sensory input is required for callosal axon targeting in the somatosensory
      cortex.
AB  - BACKGROUND: Sensory input is generally thought to be necessary for refining and
      consolidating neuronal connections during brain development. We here report that
      cortical callosal axons in somatosensory cortex require sensory input for their
      target selection in contralateral cortex. RESULTS: Eliminating sensory input to
      either hemisphere by unilateral transection of infraorbital nerve (ION) prevents
      target selection of callosal axons in contralateral cortex. Strikingly, blocking
      sensory input bilaterally, by simultaneously transecting both IONs, results in
      rescued callosal projection. In contrast, non-simultaneous bilateral ION
      transection has the same effect as unilateral transection. Similar results are
      obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain
      slices treated with KCl is decreased more in contralateral cortex with unilateral
      removal of sensory input, but decreased similarly in both cortices in mice with
      simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical
      neurons is also reduced in contralateral cortex with the unilateral removal of
      sensory input, but equally reduced on both sides with the bilateral removal of
      sensory input, suggesting that unbalanced bilateral sensory input might lead to
      mismatched neuronal activity between the two cortices and contribute to the
      formation of callosal projection. CONCLUSION: Our data demonstrate a critical
      role of balanced bilateral somatosensory input in the formation of callosal
      connections, and thus reveal a new role of sensory input in wiring brain
      circuits.

PMID- 24305169
TI  - On the amyloid datasets used for training PAFIG--how (not) to extend the
      experimental dataset of hexapeptides.
AB  - BACKGROUND: Amyloids are proteins capable of forming aberrant intramolecular
      contact sites, characteristic of beta zipper configuration. Amyloids can underlie
      serious health conditions, e.g. Alzheimer's or Parkinson's diseases. It has been
      proposed that short segments of amino acids can be responsible for protein
      amyloidogenicity, but no more than two hundred such hexapeptides have been
      experimentally found. The authors of the computational tool Pafig published in
      BMC Bioinformatics a method for extending the amyloid hexapeptide dataset that
      could be used for training and testing models. They assumed that all hexapeptides
      belonging to an amyloid protein can be regarded as amylopositive, while those
      from proteins never reported as amyloid are always amylonegative. Here we show
      why the above described method of extending datasets is wrong and discuss the
      reasons why the incorrect data could lead to falsely correct classification.
      RESULTS: The amyloid classification of hexapeptides by Pafig was confronted with
      the classification results from different state of the art computational methods
      and the outputs of all methods were studied by clustering analysis. The
      clustering methods show that Pafig is an outlier with regard to other approaches.
      Our study of the statistical patterns of its training and testing datasets showed
      a strong bias towards STVIIE hexapeptide in their positive part. Different
      statistical patterns of seemingly amylo-positive and -negative hexapeptides allow
      for a repeatable classification, which is not related to amyloid propensity of
      the hexapetides. CONCLUSIONS: Our study on recognition of amyloid hexapeptides
      showed that occurrence of incidental patterns in wrongly selected datasets can
      produce falsely correct results of classification. The assumption that all
      hexapeptides belonging to amyloid protein can be regarded as amylopositive and
      those from proteins never reported as amyloid are always amylonegative is not
      supported by any other computational method. This is in line with experimental
      observations that amyloid propensity of a full protein can result from only one
      amyloidogenic fragment in this protein, while the occurrence of amyliodogenic
      part that is well hidden inside the protein may never lead to fibril formation.
      This leads to the conclusion that Pafig does not provide correct classification
      with regard to amyloidogenicity.

PMID- 24305171
TI  - Medical relief for the 2011 Japan earthquake: a nursing account.
AB  - In 2011 the east coast of Japan experienced a massive earthquake which triggered
      a devastating tsunami destroying many towns and killing over 15 000 people. The
      work presented in this paper is a personal account that outlines the relief
      efforts of the Humanitarian Medical Assistance team and describes the efforts to
      provide medical assistance to evacuees. The towns most affected had a large
      proportion of older people who were more likely to have chronic conditions and
      required medication to sustain their health. Since personal property was
      destroyed in the tsunami many older people were left without medication and also
      did not remember which type of medication they were taking. Some evacuees had
      brought a list of their medication with them, this assisted relief teams in
      obtaining the required medication for these people. The more successful
      evacuation centers had small numbers of evacuees who were given tasks to
      administer the center that kept them occupied and active. 

PMID- 24305170
TI  - Novel CYP2A6 variants identified in African Americans are associated with slow
      nicotine metabolism in vitro and in vivo.
AB  - OBJECTIVE: Nicotine, the main addictive ingredient in tobacco, is metabolically
      inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Considerable
      genetic variation in the CYP2A6 gene results in large variation in the rates of
      nicotine metabolism, which in turn alters smoking behaviours (e.g. amount of
      cigarettes smoked, risk for dependence and success in smoking cessation). The aim
      of this study was to identify and characterize novel variants in CYP2A6.
      MATERIALS AND METHODS: The CYP2A6 gene from African American phenotypically slow
      nicotine metabolizers was sequenced and seven novel variants were identified
      [CYP2A6*39 (V68M), CYP2A6*40 (I149M), CYP2A6*41 (R265Q), CYP2A6*42 (I268T),
      CYP2A6*43 (T303I), CYP2A6*44 (E390K), CYP2A6*44 (L462P)]. Variants were
      introduced into a bi-cistronic cDNA expression construct containing CYP2A6 and
      P450 oxidoreductase and assessed for protein expression, enzymatic activity and
      stability as evaluated using western blotting and nicotine metabolism. Genotyping
      assays were developed and allelic frequencies were assessed in 534 African
      Americans. RESULTS: The variants showed significantly lower protein expression
      (P<0.001) when compared with the wild-type as well as reduced metabolism of
      nicotine to cotinine when controlling for cDNA expression using P450
      oxidoreductase (P<0.001). The variants also showed reduced stability at 37
      degrees C. Allelic frequencies ranged from 0.1 to 0.6% with a collective genotype
      frequency of 3.2%; the impact in vitro correlated significantly with in-vivo
      activity (R(2)=0.40-0.48, P<0.05). Together, those with a novel variant had
      significantly lower nicotine metabolism in vivo than those without genetic
      variants (P<0.01). CONCLUSION: Here, we identified a number of novel variants
      with reduced/loss of CYP2A6 activity, increasing our understanding of CYP2A6
      genetic variability.

PMID- 24305172
TI  - Genetic control of reproduction in dairy cows.
AB  - The advent of AI has markedly improved the production potential of dairy cows in
      all systems of production and transformed the dairy industry in many countries.
      Unfortunately, for many years breeding objectives focused solely on milk
      production. This resulted in a major decline in genetic merit for fertility
      traits. In recent years, the underlying physiological mechanisms responsible for
      this decline have started to be unravelled. It is apparent that poor genetic
      merit for fertility traits is associated with multiple defects across a range of
      organs and tissues that are antagonistic to achieving satisfactory fertility
      performance. The principal defects include excessive mobilisation of body
      condition score, unfavourable metabolic status, delayed resumption of cyclicity,
      increased incidence of endometritis, dysfunctional oestrus expression and
      inadequate luteal phase progesterone concentrations. On a positive note, it is
      possible to identify sires that combine good milk production traits with good
      fertility traits. Sire genetic merit for daughter fertility traits is improving
      rapidly in the dairy breeds, including the Holstein. With advances in animal
      breeding, especially genomic technologies, to identify superior sires, genetic
      merit for fertility traits can be improved much more quickly than they initially
      declined. 

PMID- 24305173
TI  - Reproductive technologies and genomic selection in dairy cattle.
AB  - Genomic tools are now available for most livestock species and are used routinely
      for genomic selection (GS) in cattle. One of the most important developments
      resulting from the introduction of genomic testing for dairy cattle is the
      application of reasonably priced low-density single nucleotide polymorphism
      technology in the selection of females. In this context, combining genome testing
      and reproductive biotechnologies in young heifers enables new strategies to
      generate replacement and elite females in a given period of time. Moreover,
      multiple markers have been detected in biopsies of preimplantation stage embryos,
      thus paving the way to develop new strategies based on preimplantation diagnosis
      and the genetic screening of embryos. Based on recent advances in GS, the present
      review focuses on new possibilities inherent in reproductive technologies used
      for commercial purposes and in genetic schemes, possible side effects and
      beneficial impacts on reproductive efficiency. A particular focus is on the
      different steps allowing embryo genotyping, including embryo micromanipulation,
      DNA production and quality assessment. 

PMID- 24305174
TI  - Molecular signatures of bovine embryo developmental competence.
AB  - Assessment of the developmental capacity of early bovine embryos is still an
      obstacle. Therefore, the present paper reviews all current knowledge with respect
      to morphological criteria and environmental factors that affect embryo quality.
      The molecular signature of an oocyte or embryo is considered to reflect its
      quality and to predict its subsequent developmental capacity. Therefore, the
      primary aim of the present review is to provide an overview of reported
      correlations between molecular signatures and developmental competence. A
      secondary aim of this paper is to present some new strategies to enable
      concomitant evaluation of the molecular signatures of specific embryos and
      individual developmental capacity. 

PMID- 24305176
TI  - Ultrasound biomicroscopy: a non-invasive approach for in vivo evaluation of
      oocytes and small antral follicles in mammals.
AB  - The use of ultrasonography has changed our understanding of the ovarian function
      in live animals. However, most of the studies that have used ultrasonography to
      image the ovary have provided data only of structures >1mm in diameter. The
      recent availability of high-resolution ultrasound technology with high-frequency
      transducers (25-70 MHz), offers the potential to examine the developmental
      dynamics of small antral follicles and the cumulus-oocyte complex (COC) in vivo.
      In this review we provide data from a series of studies performed by Veterinary
      Biomedical Sciences Laboratory describing the advantages and disadvantages, as
      well as image characteristics, of ultrasound biomicroscopy (UBM) to study ovarian
      biology in mammals. Data and images of small ovarian structures in rabbits,
      cattle, mice and humans are shown. The UBM technique allowed visualisation of
      small antral follicles ranging in size from 300 to 700 MUm in all species
      examined, as well as COC within follicles in rabbits, cattle and humans.
      Furthermore, UBM permitted clear distinction of the follicular wall from the
      surrounding ovarian stroma in cattle and humans. At present, the limited depth of
      penetration of UBM restricts the use of this technique to an experimental
      setting. In that regard, further studies using UBM will probably result in a
      greater understanding of the pattern and control of early antral folliculogenesis
      and oogenesis.

PMID- 24305177
TI  - Morphometric analysis of human embryos to predict developmental competence.
AB  - Morphometric and morphokinetic approaches toward embryo quality assessment have
      for many years been difficult due to technical limitations. Today, with
      improvements in laboratory techniques and subsequent quality, we have a better
      understanding of the morphometric and kinetics of embryo development. Fertility
      clinics are moving from "sensing" embryo quality to measuring embryo quality--and
      this is happening every day in fertility clinics all over the world. However, we
      cannot select for something that is not there. In daily clinical life it is
      almost never a question of selecting the optimal embryo, but rather choosing and
      prioritising between the available embryos. Data suggest that only approximately
      5% of aspirated human oocytes have the competence to implant and develop into a
      child and that, in most treatment cycles, there is no oocyte capable of
      implanting. The most likely outcome is a negative pregnancy test, no matter what
      we choose in the laboratory. Still, both with the increasing complexity of
      infertile patients treated today and the important focus on reducing multiple
      pregnancies, it becomes increasingly important to improve our ability to predict
      the developmental competence of each embryo. This involves an improved
      understanding of the basic biology controlling early embryonic development and,
      over the years, many groups have tried to identify parameters reflecting
      embryonic competence.

PMID- 24305175
TI  - Embryotropic actions of follistatin: paracrine and autocrine mediators of oocyte
      competence and embryo developmental progression.
AB  - Despite several decades since the birth of the first test tube baby and the first
      calf derived from an in vitro-fertilised embryo, the efficiency of assisted
      reproductive technologies remains less than ideal. Poor oocyte competence is a
      major factor limiting the efficiency of in vitro embryo production. Developmental
      competence obtained during oocyte growth and maturation establishes the
      foundation for successful fertilisation and preimplantation embryonic
      development. Regulation of molecular and cellular events during fertilisation and
      embryo development is mediated, in part, by oocyte-derived factors acquired
      during oocyte growth and maturation and programmed by factors of follicular
      somatic cell origin. The available evidence supports an important intrinsic role
      for oocyte-derived follistatin and JY-1 proteins in mediating embryo
      developmental progression after fertilisation, and suggests that the paracrine
      and autocrine actions of oocyte-derived growth differentiation factor 9, bone
      morphogenetic protein 15 and follicular somatic cell-derived members of the
      fibroblast growth factor family impact oocyte competence and subsequent embryo
      developmental progression after fertilisation. An increased understanding of the
      molecular mechanisms mediating oocyte competence and stage-specific developmental
      events during early embryogenesis is crucial for further improvements in assisted
      reproductive technologies. 

PMID- 24305178
TI  - Role of stem cells in large animal genetic engineering in the TALENs-CRISPR era.
AB  - The establishment of embryonic stem cells (ESCs) and gene targeting technologies
      in mice has revolutionised the field of genetics. The relative ease with which
      genes can be knocked out, and exogenous sequences introduced, has allowed the
      mouse to become the prime model for deciphering the genetic code. Not
      surprisingly, the lack of authentic ESCs has hampered the livestock genetics
      field and has forced animal scientists into adapting alternative technologies for
      genetic engineering. The recent discovery of the creation of induced pluripotent
      stem cells (iPSCs) by upregulation of a handful of reprogramming genes has
      offered renewed enthusiasm to animal geneticists. However, much like ESCs,
      establishing authentic iPSCs from the domestic animals is still beset with
      problems, including (but not limited to) the persistent expression of
      reprogramming genes and the lack of proven potential for differentiation into
      target cell types both in vitro and in vivo. Site-specific nucleases comprised of
      zinc finger nucleases (ZFNs), transcription activator-like effector nucleases
      (TALENs) and clustered regulated interspaced short palindromic repeats (CRISPRs)
      emerged as powerful genetic tools for precisely editing the genome, usurping the
      need for ESC-based genetic modifications even in the mouse. In this article, in
      the aftermath of these powerful genome editing technologies, the role of
      pluripotent stem cells in livestock genetics is discussed. 

PMID- 24305179
TI  - Editing livestock genomes with site-specific nucleases.
AB  - Over the past 5 years there has been a major transformation in our ability to
      precisely manipulate the genomes of animals. Efficiencies of introducing precise
      genetic alterations in large animal genomes have improved 100000-fold due to a
      succession of site-specific nucleases that introduce double-strand DNA breaks
      with a specificity of 10(-9). Herein we describe our applications of site
      specific nucleases, especially transcription activator-like effector nucleases,
      to engineer specific alterations in the genomes of pigs and cows. We can
      introduce variable changes mediated by non-homologous end joining of DNA breaks
      to inactive genes. Alternatively, using homology-directed repair, we have
      introduced specific changes that support either precise alterations in a gene's
      encoded polypeptide, elimination of the gene or replacement by another unrelated
      DNA sequence. Depending on the gene and the mutation, we can achieve 10%-50%
      effective rates of precise mutations. Applications of the new precision genetics
      are extensive. Livestock now can be engineered with selected phenotypes that will
      augment their value and adaption to variable ecosystems. In addition, animals can
      be engineered to specifically mimic human diseases and disorders, which will
      accelerate the production of reliable drugs and devices. Moreover, animals can be
      engineered to become better providers of biomaterials used in the medical
      treatment of diseases and disorders. 

PMID- 24305180
TI  - Directional freezing of spermatozoa and embryos.
AB  - Directional freezing is based on a simple thermodynamic principle whereby the
      sample is moved through a predetermined temperature gradient at a velocity that
      determines the cooling rate. Directional freezing permits a precise and uniform
      cooling rate in small- and large-volume samples. It avoids supercooling and
      reduces mechanical damage caused by crystallisation. Directional solidification
      was used to date for slow and rapid freezing, as well as for vitrification of
      oocytes and embryos by means of the minimum drop size technique: small drops are
      placed on a microscope slide that is moved at high velocity from the hot base to
      the cold base. Sperm samples from a wide range of domestic and wild animals were
      successfully cryopreserved using the directional freezing method. The bovine
      sexed semen industry may benefit from the increased survival of spermatozoa after
      directional freezing. 

PMID- 24305182
TI  - Parental diet, pregnancy outcomes and offspring health: metabolic determinants in
      developing oocytes and embryos.
AB  - The periconceptional period, embracing the terminal stages of oocyte growth and
      post-fertilisation development up to implantation, is sensitive to parental
      nutrition. Deficiencies or excesses in a range of macro- and micronutrients
      during this period can lead to impairments in fertility, fetal development and
      long-term offspring health. Obesity and genotype-related differences in regional
      adiposity are associated with impaired liver function and insulin resistance, and
      contribute to fatty acid-mediated impairments in sperm viability and oocyte and
      embryo quality, all of which are associated with endoplasmic reticulum stress and
      compromised fertility. Disturbances to maternal protein metabolism can elevate
      ammonium concentrations in reproductive tissues and disturb embryo and fetal
      development. Associated with this are disturbances to one-carbon metabolism,
      which can lead to epigenetic modifications to DNA and associated proteins in
      offspring that are both insulin resistant and hypertensive. Many enzymes involved
      in epigenetic gene regulation use metabolic cosubstrates (e.g. acetyl CoA and S
      adenosyl methionine) to modify DNA and associated proteins, and so act as
      'metabolic sensors' providing a link between parental nutritional status and gene
      regulation. Separate to their genomic contribution, spermatozoa can also
      influence embryo development via direct interactions with the egg and by seminal
      plasma components that act on oviductal and uterine tissues. 

PMID- 24305181
TI  - Mammalian fertility preservation through cryobiology: value of classical
      comparative studies and the need for new preservation options.
AB  - Human-related fertility preservation strategies have enormous potential for
      helping sustain and protect other species, especially to assist managing or
      'rescuing' the genomes of genetically valuable individuals, including endangered
      species. However, wider-scale applications are limited by significant
      physiological variations among species, as well as a lack of fundamental
      knowledge of basic reproductive traits and cryosensitivity. Systematic and
      comparative cryopreservation studies (e.g. on membrane biophysical properties and
      resilience to freezing temperatures) are required to successfully recover gametes
      and gonadal tissues after thawing and eventually produce healthy offspring. Such
      data are currently available for humans and a few laboratory and livestock
      animals, with virtually all other species, including wildlife, having gone
      unstudied. Interestingly, there also are commonalities among taxa that allow a
      protocol developed for one species to provide useful information or guidance for
      another. However, when a rare animal unexpectedly dies there is no time for a
      prospective understanding of that species' biophysical traits. Because the odds
      of success will be much lower in such instances, it is essential that more
      fundamental studies be directed at more species. But also worthwhile is thinking
      beyond these systematic characterisations to consider the potential of a
      'universal preservation protocol' for animal biomaterials. 

PMID- 24305411
TI  - Recipient of the 2014 IETS Pioneer Award: William W. (Bill) Thatcher, MS, PhD.

PMID- 24305412
TI  - Nitrite-induced hepatotoxicity in Bluntsnout bream (Megalobrama amblycephala):
      the mechanistic insight from transcriptome to physiology analysis.
AB  - Previous studies have investigated the physiological responses to acute nitrite
      exposure in fish; however, little information is available for the underlying
      molecular mechanisms of nitrite toxicity in aquatic ecosystems. In an effort to
      understand the underlying mechanisms of nitrite tolerance and to illuminate
      global gene expression patterns modulated by nitrite toxicity, we sampled livers
      from juvenile Megalobrama amblycephala exposed in 0.1, 15 and 30 mg L(-1) nitrite
      and performed short read (100 bp) next generation RNA sequencing (RNA-seq). The
      RNA-seq reads from all the exposures (~24 million reads) were assembled into
      unigenes datasets according to an available reference transcriptome. Using reads
      from each nitrite concentration, we performed RNA-seq based gene expression
      analysis that identified a total of 357 differentially expressed genes. The
      differentially expressed genes were related to oxidative stress, apoptotic
      pathway, oxygen transport, immune responses and the metabolism of proteins and
      fats. Quantitative real-time polymerase chain reaction using six genes
      independently verified the RNA-seq results, the present study suggests several
      new candidate genes commonly regulated in liver of M. amblycephala. In addition
      to liver histology examinations, this study provides important mechanistic
      insights into nitrite-induced liver toxicity in a whole-animal physiology
      context, which will help in understanding the syndromes caused by nitrite
      poisoning.

PMID- 24305413
TI  - Effects of a rotating electric field on the properties of epitaxial (001)
      Pb(Zr,Ti)O3 ultrathin film: a first-principles-based study.
AB  - Pb(Zr,Ti)O3 ultrathin films under open-circuit electrical boundary conditions and
      subjected to an electric field rotating in the (1-10) plane are investigated via
      the use of an effective Hamiltonian, for different magnitudes of this field.
      Varying the direction and magnitude of the electric field leads to specific
      reorganization of dipoles into original configuration states, whose
      microstructures and macroscopic properties are revealed. In particular, a novel
      (direction of the electric field-versus-magnitude of the electric field) phase
      diagram is reported here. The field-induced correlation between the polar
      distortions and the oxygen octahedral tilting is also discussed.

PMID- 24305414
TI  - NKG2C gene deletion in the Mexican population and lack of association to
      respiratory viral infections.
AB  - Expansion of a natural killer (NK) cell population that expresses NKG2C has been
      associated with cytomegalovirus and other viral infections. It has been suggested
      that this cell population may play a role in infection control. Deletion of the
      NKG2C gene (homozygous or heterozygous) has been reported with high prevalence in
      European and Asian populations. However, the effect of NKG2C genotype on NK cell
      responses to infection remains poorly defined. We determined the prevalence of
      the NKG2C deletion in a Mexican population (n = 300) and in a group of patients
      (n = 131) to assess whether NKG2C genotype affects the incidence of symptomatic
      viral infections caused by influenza or respiratory syncytial virus. The
      frequency of the NKG2C deletion haplotype in Mexican mestizos was significantly
      lower (10.3%) than that reported in other populations (17.5-21.9%). No difference
      in the prevalence of NKG2C deletion was observed in subjects with viral
      infections compared with the reference population. In addition, no differences in
      clinical characteristics and infection outcome were observed between patients
      with and without the NKG2C gene deletion. Our results indicate that copy number
      variation in the NKG2C gene has no impact on the severity of respiratory viral
      infections.

PMID- 24305415
TI  - Penetrating arterial trauma to the limbs: outcome of a modified protocol.
AB  - BACKGROUND: Penetrating arterial injuries to the limbs are common injuries in
      high volume trauma centers. Their overall surgical results reported in the
      literature are satisfactory - apart of those of the popliteal artery that still
      may lead to a significant incidence in amputations. With the present study we
      assessed our outcome with penetrating arterial injuries to the limb as to see if
      the direct involvement of vascular surgeons in the management of popliteal artery
      injuries leads to an improved (lowered) amputation rate. Results were benchmarked
      with our published results from previous years. METHODS: All patients sustaining
      penetrating arterial injuries to the limbs admitted to the Chris Hani Baragwanath
      Academic Hospital during an 18- month period ending in September 2011 were
      included in this study. Axillary, brachial and femoral artery injuries were
      operated on by the trauma surgeons as in the past. All popliteal artery injuries
      were operated on by the vascular surgeons (new). RESULTS: There were a total of
      113 patients with 116 injuries, as some patients had multiple vascular injuries:
      10 axillary, 47 brachial, 34 femoral and 25 popliteal artery injuries. Outcome of
      axillary, brachial and femoral artery injury repair were excellent and not
      significantly different from our previous reported experience. Injury to the
      popliteal artery showed a diminished re-exploration rate from 34% down to 10% (p
      = 0,049) and a decrease of amputation rate from 16% to 11% which was
      statistically not significant (p = 0,8). CONCLUSION: Penetrating arterial trauma
      to the axillary, brachial and femoral artery is followed by excellent results
      when operated by trauma surgeons. In the case of popliteal artery injury operated
      by the vascular surgeons, the results of this study do not show any statistically
      significant difference related to amputation rate from our previous reported
      studies when operated by trauma surgeons. Taking into consideration the
      diminished re-exploration rate and a tendency to a lower amputation rate, we feel
      that there is possible tendency of better outcome if operated by vascular
      surgeons. Multicenter studies with large number of enrolled patients will be
      required to prove the validity of this suggestion.

PMID- 24305417
TI  - A novel gene therapy strategy using secreted multifunctional anti-HIV proteins to
      confer protection to gene-modified and unmodified target cells.
AB  - Current human immunodeficiency virus type I (HIV) gene therapy strategies focus
      on rendering HIV target cells non-permissive to viral replication. However, gene
      modified cells fail to accumulate in patients and the virus continues to
      replicate in the unmodified target cell population. We have designed lentiviral
      vectors encoding secreted anti-HIV proteins to protect both gene-modified and
      unmodified cells from infection. Soluble CD4 (sCD4), a secreted single chain
      variable fragment (sscFv(17b)) and a secreted fusion inhibitor (sFI(T45)) were
      used to target receptor binding, co-receptor binding and membrane fusion,
      respectively. Additionally, we designed bi- and tri-functional fusion proteins to
      exploit the multistep nature of HIV entry. Of the seven antiviral proteins
      tested, sCD4, sCD4-scFv(17b), sCD4-FI(T45) and sCD4-scFv(17b)-FI(T45) efficiently
      inhibited HIV entry. The neutralization potency of the bi-functional fusion
      proteins sCD4-scFv(17b) and sCD4-FI(T45) was superior to that of sCD4 and the
      Food and Drug Administration-approved fusion inhibitor T-20. In co-culture
      experiments, sCD4, sCD4-scFv(17b) and sCD4-FI(T45) secreted from gene-modified
      producer cells conferred substantial protection to unmodified peripheral blood
      mononuclear cells. In conclusion, continuous delivery of secreted anti-HIV
      proteins via gene therapy may be a promising strategy to overcome the limitations
      of the current treatment.

PMID- 24305416
TI  - Therapeutic safety of high myocardial expression levels of the molecular inotrope
      S100A1 in a preclinical heart failure model.
AB  - Low levels of the molecular inotrope S100A1 are sufficient to rescue post
      ischemic heart failure (HF). As a prerequisite to clinical application and to
      determine the safety of myocardial S100A1 DNA-based therapy, we investigated the
      effects of high myocardial S100A1 expression levels on the cardiac contractile
      function and occurrence of arrhythmia in a preclinical large animal HF model. At
      2 weeks after myocardial infarction domestic pigs presented significant left
      ventricular (LV) contractile dysfunction. Retrograde application of AAV6-S100A1
      (1.5 * 10(13) tvp) via the anterior cardiac vein (ACV) resulted in high-level
      myocardial S100A1 protein peak expression of up to 95-fold above control. At 14
      weeks, pigs with high-level myocardial S100A1 protein overexpression did not show
      abnormalities in the electrocardiogram. Electrophysiological right ventricular
      stimulation ruled out an increased susceptibility to monomorphic ventricular
      arrhythmia. High-level S100A1 protein overexpression in the LV myocardium
      resulted in a significant increase in LV ejection fraction (LVEF), albeit to a
      lesser extent than previously reported with low S100A1 protein overexpression.
      Cardiac remodeling was, however, equally reversed. High myocardial S100A1 protein
      overexpression neither increases the occurrence of cardiac arrhythmia nor causes
      detrimental effects on myocardial contractile function in vivo. In contrast, this
      study demonstrates a broad therapeutic range of S100A1 gene therapy in post
      ischemic HF using a preclinical large animal model. 

PMID- 24305418
TI  - CD40 ligand and tdTomato-armed vaccinia virus for induction of antitumor immune
      response and tumor imaging.
AB  - Oncolytic vaccinia virus is an attractive platform for immunotherapy. Oncolysis
      releases tumor antigens and provides co-stimulatory danger signals. However,
      arming the virus can improve efficacy further. CD40 ligand (CD40L, CD154) can
      induce apoptosis of tumor cells and it also triggers several immune mechanisms.
      One of these is a T-helper type 1 (Th1) response that leads to activation of
      cytotoxic T-cells and reduction of immune suppression. Therefore, we constructed
      an oncolytic vaccinia virus expressing hCD40L (vvdd-hCD40L-tdTomato), which in
      addition features a cDNA expressing the tdTomato fluorochrome for detection of
      virus, potentially important for biosafety evaluation. We show effective
      expression of functional CD40L both in vitro and in vivo. In a xenograft model of
      bladder carcinoma sensitive to CD40L treatment, we show that growth of tumors was
      significantly inhibited by the oncolysis and apoptosis following both intravenous
      and intratumoral administration. In a CD40-negative model, CD40L expression did
      not add potency to vaccinia oncolysis. Tumors treated with vvdd-mCD40L-tdtomato
      showed enhanced efficacy in a syngenic mouse model and induced recruitment of
      antigen-presenting cells and lymphocytes at the tumor site. In summary, oncolytic
      vaccinia virus coding for CD40L mediates multiple antitumor effects including
      oncolysis, apoptosis and induction of Th1 type T-cell responses. 

PMID- 24305419
TI  - Quantitative morphological comparison of axon-targeting strategies for gene
      therapies directed to the nigro-striatal projection.
AB  - Cellular targeting of mRNAs and proteins to axons is essential for axon growth
      during development and is likely to be important for adult maintenance as well.
      Given the importance and potency of these axon-targeting motifs to the biology of
      axons, it seems possible that they can be used in the design of transgenes that
      are intended to enhance axon growth or maintenance, so as to improve potency and
      minimize off-target effects. To investigate this possibility, it is first
      essential to assess known motifs for their efficacy. We have therefore evaluated
      four axon-targeting motifs, using adeno-associated viral vector-mediated gene
      delivery in the nigro-striatal dopaminergic system, a projection that is
      predominantly affected in Parkinson's disease. We have tested two mRNA axonal
      zipcodes, the 3' untranslated region (UTR) of beta-actin and 3' UTR of tau, and
      two axonal-targeting protein motifs, the palmitoylation signal sequence in GAP-43
      and the last 15 amino acids in the amyloid precursor protein, to direct the
      expression of the fluorescent protein Tomato in axons. These sequences, fused to
      Tomato, were able to target its expression to dopaminergic axons. Based on
      quantification of Tomato-positive axons, and the density of striatal innervation,
      we conclude that the C-terminal of the amyloid precursor protein is the most
      effective axon-targeting motif. 

PMID- 24305420
TI  - Why commercialization of gene therapy stalled; examining the life cycles of gene
      therapy technologies.
AB  - This report examines the commercialization of gene therapy in the context of
      innovation theories that posit a relationship between the maturation of a
      technology through its life cycle and prospects for successful product
      development. We show that the field of gene therapy has matured steadily since
      the 1980s, with the congruent accumulation of >35 000 papers, >16 000 US patents,
      >1800 clinical trials and >$4.3 billion in capital investment in gene therapy
      companies. Gene therapy technologies comprise a series of dissimilar approaches
      for gene delivery, each of which has introduced a distinct product architecture.
      Using bibliometric methods, we quantify the maturation of each technology through
      a characteristic life cycle S-curve, from a Nascent stage, through a Growing
      stage of exponential advance, toward an Established stage and projected limit.
      Capital investment in gene therapy is shown to have occurred predominantly in
      Nascent stage technologies and to be negatively correlated with maturity. Gene
      therapy technologies are now achieving the level of maturity that innovation
      research and biotechnology experience suggest may be requisite for efficient
      product development. Asynchrony between the maturation of gene therapy
      technologies and capital investment in development-focused business models may
      have stalled the commercialization of gene therapy. 

PMID- 24305421
TI  - The biofilm, injectables, and cosmetic dermatology.

PMID- 24305422
TI  - Dyspigmentation, skin physiology, and a novel approach to skin lightening.
AB  - BACKGROUND: Even facial pigmentation is considered a universal sign of youth and
      beauty in all cultures and at all ages in both men and women. The recent FDA
      concern about the safety of topical hydroquinone has provided the impetus for
      research into new pigment lightening alternatives in the cosmetic OTC market.
      AIM: This research examined a novel hydroxyphenoxy propionic acid, ellagic acid,
      yeast extract, and salicylic acid formulation applied twice daily compared to the
      standard prescription combination of 4% hydroquinone cream and 0.025% tretinoin
      cream applied nightly. METHOD: This single-center investigator-blinded 12 week
      study enrolled 82 subjects (7 male, 75 female) ages 25-60 years divided into 2
      balanced groups of 41 subjects each with one group using a novel hydroxyphenoxy
      propionic acid, ellagic acid, yeast extract, and salicylic acid formulation
      applied twice daily compared to the standard prescription combination of 4%
      hydroquinone cream and 0.025% tretinoin cream applied nightly. RESULTS:
      Significant tolerability issues arose with the prescription combinations that
      were not seen with the cosmetic formulation. In terms of ability to even skin
      tone, decrease spot intensity, decrease spot size, and improve overall
      pigmentation, both products demonstrated parity. CONCLUSION: This research
      demonstrated the value of cosmetic formulations as part of a treatment regimen
      for pigmentation issues.

PMID- 24305423
TI  - Ultrastructure study of hair damage after ultraviolet irradiation.
AB  - BACKGROUND: Natural ultraviolet exposure induces hair damage, which is difficult
      to avoid. Most of the research work is focused on the effect of ultraviolet on
      the epidermis, dermis as well as the immune system, whereas the long-term effect
      of ultraviolet on hair has not been investigated. AIM: we performed our
      experiment to find out the changes induced in hair follicle and shaft in those
      patients exposed to high doses of ultraviolet (A and B) during treatment of other
      skin conditions. PATIENTS AND METHODS: Light and transmission electron microscopy
      examination of scalp hair follicles and shafts of 10 patients with vitiligo under
      psoralen plus ultraviolet A (group 1) and 10 patients with vitiligo under narrow
      band ultraviolet B (group 2) was carried out and compared with those of 10
      healthy volunteers (group 3). RESULTS: Physical changes in the appearance of hair
      were more in groups 1 and 2 than control. Reduced hair follicle thickness and
      perifollicular infiltrate and hyaline disorganized perifollicular collagen were
      observed more in group 1 than in group 2 with the absence of these changes in
      group 3. Transmission electron microscopy showed nonspecific cell injury in hair
      follicles in group 1 more than the other 2 groups, while the damaging effect on
      hair was more in the second group than the others. CONCLUSION: Due to the
      damaging effect of ultraviolet on hair, patients under treatment with this
      modality should be cautious to protect their hair during treatment.

PMID- 24305424
TI  - Treatment of forehead/glabellar rhytide complex with combination botulinum toxin
      a and hyaluronic acid versus botulinum toxin A injection alone: a split-face,
      rater-blinded, randomized control trial.
AB  - BACKGROUND: Forehead and glabella rhytides are treated mostly with neurotoxins,
      although some practitioners prefer the concurrent use of fillers. It has been
      suggested that combination treatments can result in a better overall improvement.
      AIMS: To compare the safety and effectiveness of treatment of forehead and
      glabellar lines with botulinum toxin A alone versus botulinum toxin A and filler.
      METHODS: Split-face, randomized control trial. Twenty subjects with
      forehead/glabellar rhytide complex (static and dynamic creases) enrolled.
      Subjects were randomized and injected with botulinum toxin alone on one side of
      the forehead/glabella and hyaluronic acid filler followed by botulinum toxin on
      the other side. Blinded ratings were obtained to assess the effectiveness of
      treatment for static and dynamic rhytides, respectively, at 2-week, 6-week, 3
      month, and 6-month follow-up visits. Subjects performed a self-evaluation at the
      end of the study. Adverse events were recorded. RESULTS: Ratings of both
      treatments showed comparable efficacy, with 100% of subjects experiencing
      improvement from baseline regardless of treatment type at weeks 2, 6, and 12.
      Combination treatment produced longer-lasting results in dynamic forehead
      wrinkles, and greater static and dynamic wrinkle reduction in the glabella at
      week 24. Subject self-evaluations showed that both treatments were effective,
      with a nominal preference for combination treatment. CONCLUSIONS: Glabella and
      forehead lines can be effectively and safely reduced with neurotoxin alone as
      well as neurotoxin in combination with fillers. Combination treatment may provide
      a slightly better cumulative benefit and also increase the persistence of effect.

PMID- 24305425
TI  - Quality of life in postmenopausal women: translation and validation of MSkinQOL
      questionnaire to measure the effect of a skincare product in USA.
AB  - OBJECTIVES: The 28-item Menopausal Skin Quality Of Life (MSkinQOL), a previously
      validated French questionnaire, developed to assess psychological features of
      menopausal women and to measure the benefits of using cosmetic skincare products
      was translated and validated to assess a skincare product in the USA. METHODS:
      Construct validity, reliability, reproducibility, and responsiveness were
      assessed with two groups of 100 nonmenopausal (NM) and 100 postmenopausal (PM)
      women. The group of PM women applied a specially developed skincare product twice
      daily for 1 month and filled in the same questionnaire after 1 month as well as a
      general self-assessment questionnaire about the efficacy and cosmetic properties
      of the product. RESULTS: No ceiling or floor effects were identified. Construct
      and internal validity was assessed using a multitrait analysis: questionnaire
      items proved closely correlated, and each dimension covers a different aspect of
      women answers profile. The three dimensions showed good reliability and
      stability. Baseline values for social effects of skin appearance, health status,
      and self-esteem were significantly different between PM and NM volunteers. Values
      of these three dimensions were significantly improved after 2 weeks of product
      application, and further improved after 4 weeks. CONCLUSION: This study shows
      that a careful translation and a rigorous process of validation lead to a
      reliable tool adapted to each country to explore and measure quality of life in
      healthy PM women.

PMID- 24305426
TI  - Novel use of polymethyl methacrylate (PMMA) microspheres in the treatment of
      infraorbital rhytids.
AB  - AIM: To demonstrate safely with the use of polymethyl methacrylate (PMMA)
      microspheres in the infraorbital eyelid area using a deliberate conservative
      injection in the treatment of rhytids. METHODS: A retrospective case series of
      289 patients in an outpatient cosmetic dermatology clinic evaluated and treated
      by one senior provider (NM) of infraorbital rhytids with PMMA from December 2010
      to March 2011. Statistical analysis was performed for race, skin type, history of
      hypertrophic scar, autoimmunity, history of "sensitive skin" and history of prior
      procedures such as prior facelift, rhinoplasty, and blepharoplasty. RESULTS: Two
      hundred ninety-one patients underwent at least 1-6 injections of PMMA
      microspheres into bilateral under eye area. Early complications were edema and
      ecchymosis. Late complications were identified in 4 of 289 patients who developed
      small granulomas. All patients who developed granulomas had had a previous lower
      blepharoplasty (P = 0.00). A history of "sensitive skin" was approaching
      statistical significance (P = 0.15). CONCLUSION: This study has shown that PMMA
      microsphere injection is a safe subdermal technique in the correction of
      infraorbital rhytids. Safety was demonstrated in 289 patients with only 4 minor
      complications of small lateral granuloma which all resolved within 4 weeks after
      intralesion triamcinolone injection. However, this is an off-label use of a
      permanent filler not approved for use in the infraorbits and significant caution
      must be taken with full disclosure to the patient leading to informed consent.
      Caution in PMMA microsphere injection should be given in the patient with prior
      blepharoplasty. The advantage of PMMA microsphere is that the result seems to be
      predictable and natural.

PMID- 24305427
TI  - Protective effects of skin permeable epidermal and fibroblast growth factor
      against ultraviolet-induced skin damage and human skin wrinkles.
AB  - BACKGROUND: Epidermal and fibroblast growth factor (EGF and FGF1) proteins play
      an important role in the regeneration and proliferation of skin cells. EGF and
      FGF1 have considerable potential as possible therapeutic or cosmetic agents for
      the treatment of skin damage including wrinkles. OBJECTIVES: Using protein
      transduction domains (PTD), we investigated whether PTD-EGF and FGF1 transduced
      into skin cells and tissue. Transduced proteins showed protective effects in a UV
      induced skin damage model as well as against skin wrinkles. METHODS: Transduced
      PTD-EGF and FGF1 proteins were detected by immunofluorescence and
      immunohistochemistry. The effects of PTD-EGF and FGF1 were examined by WST assay,
      Western blotting, immunohistochemistry, and skin wrinkle parameters. RESULTS: The
      PTD-EGF and FGF1 increased cell proliferation and collagen type 1 alpha 1 protein
      accumulation in skin tissue. Also, PTD-EGF and FGF1 inhibited UV-induced skin
      damage. Furthermore, topical application of PTD-EGF and FGF1 contained ampoules
      which were considered to improve the wrinkle parameters of human skin.
      CONCLUSION: These results show that PTD-EGF and FGF1 can be a potential
      therapeutic or cosmetic agent for skin damaged and injury including wrinkles and
      aging.

PMID- 24305428
TI  - A promising split-lesion technique for rapid tattoo removal using a novel
      sequential approach of a single sitting of pulsed CO(2) followed by Q-switched
      Nd: YAG laser (1064 nm).
AB  - BACKGROUND: Laser tattoo removal conventionally uses Q-switched (QS) lasers, but
      they require multiple sittings, and the end results depend largely on the type of
      tattoo treated. In pigmented skin, due to the competing epidermal pigment
      results, laser results in tattoo are slow and inadequate. OBJECTIVE: To evaluate
      the efficacy of a combined use of ultrapulse CO2 and QS Nd:YAG (1064 nm) laser in
      the treatment of tattoos in Indian skin. MATERIALS AND METHODS: A split-lesion
      trial was carried out in five patients, with the left side of tattoos receiving
      the QS Nd:YAG (1064 nm) and the right side, a sequential combination of Up CO2
      and QS Nd: YAG at 6 weeks interval with a maximum of six sittings. Outcome
      assessment was carried out by a blinded assessor using standardized photography.
      An assessment of physician improvement score, side-effects score, and patient
      satisfaction score was taken during and at the end of the study. RESULTS: There
      was a statistically significant improvement on the combination side(physician
      improvement score -3.7 vs. 1.87: P = 0.0019) which occurred earlier with fewer
      sittings (1.7 vs. 6). There was no statistically significant difference in the
      side effects. CONCLUSION: A combination of an Up CO2 laser with QS Nd: YAG laser
      is a promising tool for rapid and effective removal of blue-black/blue amateur
      tattoo in pigmented skin.

PMID- 24305429
TI  - Honey in dermatology and skin care: a review.
AB  - Honey is a bee-derived, supersaturated solution composed mainly of fructose and
      glucose, and containing proteins and amino acids, vitamins, enzymes, minerals,
      and other minor components. Historical records of honey skin uses date back to
      the earliest civilizations, showing that honey has been frequently used as a
      binder or vehicle, but also for its therapeutic virtues. Antimicrobial properties
      are pivotal in dermatological applications, owing to enzymatic H2 O2 release or
      the presence of active components, like methylglyoxal in manuka, while medical
      grade honey is also available. Honey is particularly suitable as a dressing for
      wounds and burns and has also been included in treatments against pityriasis,
      tinea, seborrhea, dandruff, diaper dermatitis, psoriasis, hemorrhoids, and anal
      fissure. In cosmetic formulations, it exerts emollient, humectant, soothing, and
      hair conditioning effects, keeps the skin juvenile and retards wrinkle formation,
      regulates pH and prevents pathogen infections. Honey-based cosmetic products
      include lip ointments, cleansing milks, hydrating creams, after sun, tonic
      lotions, shampoos, and conditioners. The used amounts range between 1 and 10%,
      but concentrations up to 70% can be reached by mixing with oils, gel, and
      emulsifiers, or polymer entrapment. Intermediate-moisture, dried, and chemically
      modified honeys are also used. Mechanisms of action on skin cells are deeply
      conditioned by the botanical sources and include antioxidant activity, the
      induction of cytokines and matrix metalloproteinase expression, as well as
      epithelial-mesenchymal transition in wounded epidermis. Future achievements,
      throwing light on honey chemistry and pharmacological traits, will open the way
      to new therapeutic approaches and add considerable market value to the product. 

PMID- 24305430
TI  - Hydrophobically modified polymers can minimize skin irritation potential caused
      by surfactant-based cleansers.
AB  - INTRODUCTION: The addition of hydrophobically modified polymers (HMPs) to
      cleansers that contain surfactants can create polymer-surfactant complexes that
      are less irritating to the skin than commercially available mild cleansers. Our
      objective was to compare the tolerability and efficacy of a test foaming liquid
      facial cleanser containing HMPs with a commercial liquid nonfoaming facial
      cleanser in women with sensitive skin. METHODS: In this randomized, prospective,
      double-blind, comparative study, women (n = 20 per group) with mild-to-moderate
      atopic dermatitis (AD), eczema, acne, or rosacea used a test gentle foaming
      liquid facial cleanser containing HMPs or a commercial gentle liquid nonfoaming
      facial cleanser daily for 3 weeks. Investigators assessed irritation and skin
      condition. Study subjects also assessed their skin properties and the performance
      of each cleanser. RESULTS: Clinicians as well as study subjects consistently
      rated the test cleanser as effective or slightly more effective at improving
      symptoms than the commercial cleanser, although no significant differences
      between groups were observed. At weeks 1 and 3, respectively, more users of the
      commercial cleanser reported irritation (20% and 10%) than users of the test
      cleanser (5% and 5%). In addition, subject self-assessments of skin condition and
      cleansing properties were slightly more improved with the test cleanser than with
      the commercial cleanser. CONCLUSIONS: Both the test foaming cleanser containing
      HMPs and the commercial nonfoaming cleanser were effective and well accepted by
      most women in the study. Improvements were observed by both clinicians and
      subjects in the group using the test cleanser containing HMPs in all evaluated
      skin categories.

PMID- 24305431
TI  - Pigmented concealing powders for the hair loss patient.
AB  - Patients suffering from alopecia may experience low self-esteem, low self-image,
      and other psychological consequences. While medical and surgical options for
      treating hair loss exist, these may be prohibitively expensive or have an
      unpredictable outcome. In lieu of or in addition to therapeutic approaches,
      cosmetic options have long been an approach to hair loss. However, patients and
      clinicians alike often regard cosmetic options to be limited to hairstyling and
      hairpieces, unaware that newer options, namely pigmented concealing powders, may
      offer a more practical and seemingly natural camouflage. This article introduces
      the clinician to concealing powders as a viable option for the hair loss patient.

PMID- 24305432
TI  - Setting priorities for mental health care in Nepal: a formative study.
AB  - BACKGROUND: There is an urgent need to address the massive treatment gap for
      mental health problems, especially in low income settings. Packages of care
      integrated in routine primary health care are posited as a strategy to scale-up
      mental health care, yet more needs to be known about the most feasible and
      effective way to go about this. METHODS: The study follows a combined methods
      design that includes engaging an expert panel in a priority setting exercise,
      running workshops to develop a Theory of Change and conducting in-depth
      qualitative interviews and focus group discussions with key stakeholders. The
      results of each research step were taken forward to inform the subsequent one.
      RESULTS: There was strong endorsement for a system of care that encompasses both
      the perspectives of health facility and the community. Issues related to
      increasing access and demand, guaranteeing a sustainable supply of psychotropic
      medicine, adequate human resourcing, and ensuring positive family involvement
      came up as priority areas of attention. CONCLUSION: The study underlines many of
      the known barriers in developing mental health services. At the same time it
      provides a distinct pathway and concrete recommendations for overcoming these
      challenges in Nepal.

PMID- 24305433
TI  - Dynamics of VEGF matrix-retention in vascular network patterning.
AB  - Vascular endothelial growth factor (VEGF) is a central regulator of blood vessel
      morphogenesis, although its role in patterning of endothelial cells into vascular
      networks is not fully understood. It has been suggested that binding of soluble
      VEGF to extracellular matrix components causes spatially restricted cues that
      guide endothelial cells into network patterns. Yet, current evidence for such a
      mechanism remains indirect. In this study, we quantitatively analyse the dynamics
      of VEGF retention in a controlled in vitro situation of human umbilical vascular
      endothelial cells (HUVECs) in Matrigel. We show that fluorescent VEGF accumulates
      in pericellular areas and colocalizes with VEGF binding molecules. Analysis of
      fluorescence recovery after photobleaching reveals that binding/unbinding to
      matrix molecules dominates VEGF dynamics in the pericellular region.
      Computational simulations using our experimental measurements of kinetic
      parameters show that matrix retention of chemotactic signals can lead to the
      formation of reticular cellular networks on a realistic timescale. Taken
      together, these results show that VEGF binds to matrix molecules in proximity of
      HUVECs in Matrigel, and suggest that bound VEGF drives vascular network
      patterning. 

PMID- 24305434
TI  - Palliative medicine must accept responsibility for end of life care.

PMID- 24305435
TI  - Factors associated with consulting a dietitian for diabetes management: a cross
      sectional study.
AB  - BACKGROUND: Type 2 Diabetes (T2D) has reached epidemic levels in the Middle East
      region. Despite evidence that it improves health outcomes and saves health costs,
      dietary counseling for T2D remains grossly under-investigated in this region. The
      aim of this study was to assess the frequency and determinants of use of dietary
      counseling services by T2D patients in Lebanon and recommend corrective measures
      that may guide the planning, organization and delivery of care for chronic
      diseases in general and diabetes care in particular. METHODS: A non-experimental
      cross-sectional design was utilized to survey outpatients with T2D in two major
      health centers in Lebanon. Patients diagnosed with T2D were invited to complete a
      questionnaire consisting of five sections: socio-demographic characteristics,
      disease attributes, patients' perceptions regarding T2D management, practice of
      lifestyle modifications, and referral by a physician to a dietitian. The outcome
      of interest was the use of dietary counseling services by T2D patients at least
      once since their diagnosis. Descriptive statistics and logistic regression
      analyses were used to evaluate the frequency and determinants of dietary
      counseling services utilization. RESULTS: A total of 332 T2D patients completed
      the questionnaire (response rate 94.6%). Although 75% of study participants
      believed that dietitians can assist them in changing their dietary habits, only
      38% had consulted with a dietitian. Among study participants, only 34% were
      referred to a dietitian by their physician. The main determinants of the use of
      dietary counseling services were referral by a physician (OR: 112.25; 95% CI =
      42.74-294.84), the presence of outpatient social or private health insurance (OR:
      5.86; 95% CI = 2.40-14.25) and the belief that a dietitian can assist in changing
      dietary habits (OR: 3.74; 95% CI = 1.33-10.54). CONCLUSIONS: The findings of this
      study show suboptimal use of dietary counseling services by T2D patients in
      Lebanon. Key determinants were physicians' referral, financial support for
      outpatient care, and patients' belief in the usefulness of dietary counseling.
      Suggested interventions entail enhancing the planning and organization of care
      through inter-professional collaboration between physicians and dietitians;
      promoting public financing for high quality outpatient care that includes dietary
      counseling; and promoting the value of dietary counseling and improving the
      public image of dietitians.

PMID- 24305437
TI  - A non-surgical approach for male germ cell mediated gene transmission through
      transgenesis.
AB  - Microinjection of foreign DNA in male pronucleus by in-vitro embryo manipulation
      is difficult but remains the method of choice for generating transgenic animals.
      Other procedures, including retroviral and embryonic stem cell mediated
      transgenesis are equally complicated and have limitations. Although our
      previously reported technique of testicular transgenesis circumvented several
      limitations, it involved many steps, including surgery and hemicastration, which
      carried risk of infection and impotency. We improved this technique further, into
      a two step non-surgical electroporation procedure, for making transgenic mice. In
      this approach, transgene was delivered inside both testes by injection and
      modified parameters of electroporation were used for in-vivo gene integration in
      germ cells. Using variety of constructs, germ cell integration of the gene and
      its transmission in progeny was confirmed by PCR, slot blot and
      immunohistochemical analysis. This improved technique is efficient, requires
      substantially less time and can be easily adopted by various biomedical
      researchers. 

PMID- 24305438
TI  - Homogeneous crystalline FeSi2 films of c (4 * 8) phase grown on Si (111) by
      reactive deposition epitaxy.
AB  - The growth of iron silicides on Si (111) using reactive deposition epitaxy method
      was studied by scanning tunneling microscopy and X-ray photoelectron spectroscopy
      (XPS). Instead of the mixture of different silicide phases, a homogeneous
      crystalline film of c (4 * 8) phase was formed on the Si (111) surface at
      approximately 750 degrees C. Scanning tunneling spectra show that the film
      exhibits a semiconducting character with a band gap of approximately 0.85 eV.
      Compared with elemental Fe, the Fe 2p peaks of the film exhibit a lower spin
      orbit splitting (-0.3 eV) and the Fe 2p3/2 level has a smaller full-width at half
      maximum (-0.6 eV) and a higher binding energy (+0.3 eV). Quantitative XPS
      analysis shows that the c (4 * 8) phase is in the FeSi2 stoichiometry regime. The
      c (4 * 8) pattern could result from the ordered arrangement of defects of Fe
      vacancies in the buried Fe layers. 

PMID- 24305439
TI  - Cell density impacts on Candida glabrata survival in hypo-osmotic stress.
AB  - Candida glabrata cells suspended in water are under hypo-osmotic stress and
      undergo cell death in 1-2 days, unless they are at a density of more than 10(5 )
      CFU mL(-1) . The dying cells exhibit FITC-annexin V staining, indicative of
      programmed cell death (apoptosis). In a higher cell density, cells are protected
      and survive at least for 4 days. Filtrates from cells at high density can protect
      those at lower density, indicating that cells release substances, amounting to c.
      5 mg L(-1) of cell suspension, that protect each other against hypo-osmotic
      stress. In a concentrated form, the released materials can support growth,
      indicating that the protective material includes carbon and nitrogen sources, as
      well as vitamins that are required by C. glabrata for growth. We conclude that
      cell death from hypo-osmotic stress can be alleviated by small amounts of
      nutrients. 

PMID- 24305445
TI  - Putting some muscle into continuum.

PMID- 24305446
TI  - Congenital muscular dystrophies and congenital myopathies.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide information regarding
      the diagnosis and natural history of some very rare disorders: congenital
      muscular dystrophies and congenital myopathies. Patients with these conditions
      share characteristics such as early onset of weakness and severe hypotonia. Other
      organs such as the brain, eyes, and skin may be involved. Diagnosis depends
      largely on recognition of phenotype, muscle biopsy, and mutation analysis. RECENT
      FINDINGS: More than 30 genes have been associated with these diseases, most of
      which have only been recognized in the past decade. Increasing availability of
      DNA analysis has been important in decreasing delay in diagnosis. SUMMARY:
      Patients with congenital muscular dystrophy or congenital myopathy are at high
      risk of complications including restrictive lung disease, orthopedic deformities,
      seizures, cardiomyopathy, and malignant hyperthermia. Life expectancy varies with
      the severity of complications. Having an accurate and specific diagnosis allows
      the neurologist to carry out anticipatory guidance and appropriate monitoring.
      New hope exists for experimental treatments for congenital muscular dystrophy and
      congenital myopathy as our understanding of pathogenesis evolves.

PMID- 24305447
TI  - The muscular dystrophies.
AB  - PURPOSE OF REVIEW: With transition to the genetic era, the number of muscular
      dystrophies has grown significantly, but so too has our understanding of their
      pathogenic underpinnings. Clinical features associated with each muscular
      dystrophy still guide us to the diagnosis. However, improved diagnostic abilities
      refine and expand phenotypic and genotypic correlates. This article discusses the
      epidemiology, clinical features, and diagnosis of these disorders. RECENT
      FINDINGS: Some important recent advancements include (1) a much greater
      understanding of the pathogenetic pathways underlying facioscapulohumeral
      muscular dystrophy and myotonic dystrophy type 1; (2) the publication of
      diagnostic and treatment guidelines for Duchenne muscular dystrophy; and (3)
      further clarification of the many genetic muscle disorders presenting a limb
      girdle pattern of weakness. SUMMARY: Muscular dystrophies are genetic,
      progressive, degenerative disorders with the primary symptom of muscle weakness.
      Duchenne, Becker, facioscapulohumeral, and myotonic muscular dystrophies are most
      prevalent and tend to have distinctive features helpful in diagnosis. The limb
      girdle, Emery-Dreifuss, and oculopharyngeal muscular dystrophies are less common
      but often may also be diagnosed on the basis of phenotype. Researchers hope to
      help patients with future discoveries effective in slowing or halting disease
      progression, reversing or preventing underlying mechanisms, and repairing
      previously damaged muscle.

PMID- 24305448
TI  - Metabolic myopathies.
AB  - PURPOSE OF REVIEW: The metabolic myopathies result from inborn errors of
      metabolism affecting intracellular energy production due to defects in glycogen,
      lipid, adenine nucleotides, and mitochondrial metabolism. This article provides
      an overview of the most common metabolic myopathies. RECENT FINDINGS: Our
      knowledge of metabolic myopathies has expanded rapidly in recent years, providing
      us with major advances in the detection of genetic and biochemical defects. New
      and improved diagnostic tools are now available for some of these disorders, and
      targeted therapies for specific biochemical deficits have been developed (ie,
      enzyme replacement therapy for acid maltase deficiency). SUMMARY: The diagnostic
      approach for patients with suspected metabolic myopathy should start with the
      recognition of a static or dynamic pattern (fixed versus exercise-induced
      weakness). Individual presentations vary according to age of onset and the
      severity of each particular biochemical dysfunction. Additional clinical clues
      include the presence of multisystem disease, family history, and laboratory
      characteristics. Appropriate investigations, timely treatment, and genetic
      counseling are discussed for the most common conditions.

PMID- 24305450
TI  - Inflammatory myopathies.
AB  - PURPOSE OF REVIEW: To discuss the clinical, laboratory, and histopathologic
      features and presumed pathogenic mechanisms of the four major categories of
      idiopathic inflammatory myopathy, namely dermatomyositis, polymyositis, immune
      mediated necrotizing myopathy, and inclusion body myositis. RECENT FINDINGS:
      Dermatomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis
      are clinically, histologically, and pathogenically distinct. Polymyositis is a T
      cell-mediated disorder directed against muscle fibers. The pathogenesis of
      dermatomyositis, necrotizing myopathy, and inclusion body myositis are unknown.
      Dermatomyositis, polymyositis, and necrotizing myopathy are generally, but not
      always, responsive to immunosuppressive therapy, in contrast to inclusion body
      myositis, which is generally refractory to therapy. SUMMARY: The pattern of
      muscle weakness, other clinical features (eg, rash, concurrent interstitial lung
      disease), laboratory features (creatine kinase, autoantibodies), and muscle
      biopsies are useful in distinguishing subtypes of inflammatory myopathy and in
      guiding treatment. More research is necessary to unravel the exact pathogenic
      bases of these myopathies and identify better treatments.

PMID- 24305449
TI  - Muscle channelopathies: the nondystrophic myotonias and periodic paralyses.
AB  - PURPOSE OF REVIEW: The muscle channelopathies are a group of rare inherited
      diseases caused by mutations in muscle ion channels. Mutations cause an increase
      or decrease in muscle membrane excitability, leading to a spectrum of related
      clinical disorders: the nondystrophic myotonias are characterized by delayed
      relaxation after muscle contraction, causing muscle stiffness and pain; the
      periodic paralyses are characterized by episodes of flaccid muscle paralysis.
      This review describes the clinical characteristics, molecular pathogenesis, and
      treatments of the nondystrophic myotonias and periodic paralyses. RECENT
      FINDINGS: Advances have been made in both the treatment and our understanding of
      the molecular pathophysiology of muscle channelopathies: (1) a recent controlled
      trial showed that mexiletine was effective for reducing symptoms and signs of
      myotonia in nondystrophic myotonia; (2) the mechanisms by which hypokalemic
      periodic paralysis leads to a depolarized but unexcitable sarcolemma membrane
      have been traced to a novel gating pore current; and (3) an association was
      demonstrated between mutations in a potassium inward rectifier and patients with
      thyrotoxic periodic paralysis. SUMMARY: The muscle channelopathies are an
      expanding group of muscle diseases caused by mutations in sodium, chloride,
      potassium, and calcium ion channels that result in increased or decreased muscle
      membrane excitability. Recognizing patients with channelopathies and confirming
      the diagnosis is important, as treatment and management strategies differ based
      on mutation and clinical phenotype.

PMID- 24305451
TI  - Toxic myopathies.
AB  - PURPOSE: This article reviews the most important muscle toxins, many of which are
      widely prescribed medications. Particular emphasis is placed on statins, which
      cause muscle symptoms in a relatively large proportion of the patients who take
      them. RECENT FINDINGS: As with other toxic myopathies, most cases of statin
      associated myotoxicity are self-limited and subside with discontinuation of the
      offending agent. Importantly, about 2% of the population is homozygous for a
      single nucleotide polymorphism, and these individuals have a dramatically
      increased risk of self-limited statin myopathy. Much more rarely, statins trigger
      a progressive autoimmune myopathy characterized by a necrotizing muscle biopsy
      and autoantibodies recognizing hydroxymethylglutaryl coenzyme A (HMG-CoA)
      reductase, the pharmacologic target of statins. SUMMARY: In most cases, toxic
      myopathies resolve after the toxic agent is stopped. Recognizing that statins can
      cause an autoimmune necrotizing myopathy is important because patients with this
      form of statin-triggered muscle disease usually require immunosuppressive
      therapy.

PMID- 24305452
TI  - Multidisciplinary approach to the management of myopathies.
AB  - PURPOSE OF REVIEW: Aside from some inflammatory myopathies and very few genetic
      disorders, there are no therapies that make most patients with myopathies
      stronger. Consequently, the management of these patients can be frustrating for
      patients and their families as well as the clinicians taking care of them.
      Treatment of these patients must involve a comprehensive approach focused on
      limiting the secondary effects of skeletal muscle weakness, managing
      comorbidities associated with specific diseases, and, most importantly,
      optimizing patients' functional abilities and quality of life in terms of their
      ability to accomplish activities of daily living. While the approach to each
      patient differs depending on their disease, certain common themes can be
      addressed in each patient. This review highlights an approach centered on four
      conceptual themes ("the Four S's"): Strength therapies, Supportive care,
      Symptomatic therapies, and pSychological support. RECENT FINDINGS: Although
      relatively few well-designed studies have been done that highlight conservative
      management of patients with various myopathies, an emerging literature helps
      guide the clinician in certain key areas, especially in relation to cardiac and
      pulmonary management of these patients. SUMMARY: While disease-altering therapies
      have proven elusive for many muscle diseases, a multimodal approach to the
      conservative and supportive care of these patients can markedly improve their
      quality of life. Pharmacologic treatment options for specific myopathies will not
      be addressed in this article but are covered elsewhere in this issue of
      CONTINUUM.

PMID- 24305453
TI  - A pattern recognition approach to myopathy.
AB  - PURPOSE OF REVIEW: Myopathies are a heterogeneous group of disorders that can be
      challenging to diagnose. The purpose of this review is to provide a diagnostic
      approach based predominantly on the clinical history and neurologic examination.
      Laboratory testing that can subsequently be used to confirm the suspected
      diagnosis based on this pattern recognition approach will also be discussed.
      RECENT FINDINGS: Over the past decade, numerous discoveries have allowed
      clinicians to diagnose myopathies with genetic testing. Unfortunately, the
      testing is extremely expensive and frequently not covered by insurance. SUMMARY:
      Careful consideration of the pattern of muscle weakness in addition to other
      aspects of the physical examination and diagnostic testing should assist the
      clinician in making a timely and accurate diagnosis and minimize the expense of
      confirmatory genetic testing.

PMID- 24305454
TI  - The new frontier of genetically targeted therapies for muscle disease.
AB  - This article presents the case of a 5-year-old boy with Duchenne muscular
      dystrophy who is eligible to enroll in a clinical trial of gene therapy for this
      disorder. His parents are grappling with the decision about whether to enroll
      him. Among the issues under consideration are the potential risks and benefits to
      him, the costs of participating (because frequent, partially reimbursed travel is
      involved), and the potential cost savings of receiving this treatment on a
      research basis rather than as a clinically approved therapy. His parents seek the
      advice of his pediatric neurologist. After careful consideration of the various
      factors above, the pediatric neurologist explains to the family that
      participating in the trial is ethically permissible but that, given the uncertain
      benefits and potential for substantial expenses without benefit to the child,
      participation should not be regarded as ethically obligatory. 

PMID- 24305455
TI  - Administration of glucocorticoids in boys with Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the most common neuromuscular disease
      affecting boys. Advances in their care can delay the progression of DMD-related
      disability and prolong survival. The administration of glucocorticoids is among
      these advances. Glucocorticoid therapy, however, is associated with a myriad of
      potential adverse effects, and treating physicians as well as patients and their
      family members must understand the benefit/risk ratio of glucocorticoid therapy.
      Although current best evidence supports the use of glucocorticoids in patients
      with DMD, many are not offered the option. Considerable variability in practice
      also exists regarding when and how these drugs should be administered. 

PMID- 24305456
TI  - Coding issues for neuromuscular visits.

PMID- 24305460
TI  - Patient management problem.

PMID- 24305463
TI  - Increased soluble IL-2 receptor levels in serum from a patient with painless
      thyroiditis.
AB  - CONTEXT: Serum concentration of soluble interleukin-2 receptor (sIL-2R) has been
      established as a reliable marker of T-lymphocyte activation. However, there have
      been no reports describing the relationship between serum sIL-2R and painless
      thyroiditis. OBJECTIVE: We report a case of a 76-yr-old female with a significant
      and temporary increase of sIL-2R concomitant with painless thyroiditis. CASE
      ILLUSTRATION: The patient was diagnosed with malignant lymphoma at the age of 73.
      After 6 cycles of CHOP-R complete remission was induced and no recurrence was
      observed up to 3.5 years. At 76 years of age, she exhibited hyperthyroidism and
      was diagnosed with painless thyroiditis based upon US examination and 99mTc
      Thyroid scintigraphy. Her AST and ALT were mildly elevated, and her serum level
      of sIL-2R increased up to 2230 U/mL from the approximately 540 U/mL, which had
      been stable for 3 years before.These abnormal data normalized without requiring
      any treatment. The time-course of the reduction in sIL-2R did not correlate with
      FT4 or FT3, but was very similar to that of AST and ALT. CONCLUSION: There was no
      evidence of relapse of the malignant lymphoma. We conclude that the increase of
      sIL-2R was associated with painless thyroiditis. Considering the similar time
      course between the reduction of serum sIL-2R and those of AST and ALT, which are
      often accompanied by autoimmune processes in painless thyroiditis during the
      development of hyperthyroidism, it was suggested that the increase of serum sIL
      2R in this case resulted from activation of an autoimmune process.

PMID- 24305464
TI  - Poor-quality sleep is associated with metabolic syndrome in Korean adults.
AB  - Sleep disorder and metabolic syndrome (MetS) are important health-related
      problems. Recently, sleep duration has decreased among Korean adults. In this
      study, we examined whether sleep quality is associated with MetS by analyzing 301
      subjects, aged 20 years or over, without acute and severe illness who visited
      three primary care clinics. Sleep duration, sleep quality and the risk of sleep
      related breathing disorder (SRBD) were assessed with a standardized sleeping
      estimating instrument. MetS was defined according to the modified diagnostic
      criteria of the National Cholesterol Education Program Adult Treatment Panel-III
      using the Korean abdominal obesity definition. In the multiple logistic
      regression analysis, compared with the 7-hour sleep group, the adjusted odds
      ratios (ORs) of the <= 5- and >= 9-hour sleep groups for MetS were 4.89 and 5.98,
      respectively. Compared with the good-sleep quality and low-SRBD risk groups, the
      adjusted ORs of the poor-quality sleep and high-SRBD risk groups were 3.83 and
      1.92, respectively (p < 0.05). In the <= 5- and >= 9-hour sleep groups, the
      prevalence of elevated triglyceride and high HOMA-IR was higher (p = 0.069). In
      the poor-quality sleep group, the prevalence of abdominal obesity, elevated
      triglyceride, low HDL cholesterol, high fasting insulin and high HOMA-IR were
      higher. In the high-SRBD risk group, the prevalence of abdominal obesity, obesity
      and elevated triglyceride were higher (p < 0.05). Overall, the <= 5- or >= 9-hour
      sleep duration, poor-quality sleep and high-SRBD risk are related with the high
      prevalence of MetS, perhaps through elevated insulin-resistance resulting from
      adiposity. 

PMID- 24305465
TI  - Differential expression of GAP-43 protein in the rostral brain neurons of early
      chick embryos.
AB  - Brain development is composed of several processes, which are chronologically and
      mechanistically overlapping each other. However, the process of the earliest
      neural circuit formation in the rostral brain is less understood compared with
      other processes in brain development, in part because of the lack of appropriate
      molecular markers. Accordingly, the identification of molecular markers for nerve
      cells may accelerate the detailed analysis of neural development. Growth
      associated protein 43 (GAP-43) is a major growth cone protein that regulates F
      actin dynamics, and it has been often used as a marker for developing neurons. To
      test whether GAP-43 can be used as a general marker for developing neurons in
      chick early embryos, we analyzed the expression pattern of GAP-43 protein in the
      brain. While the majority of the neurons were GAP-43 positive, the earliest
      neurons in the dorsal mesencephalon (future tectum) were GAP-43 negative.
      However, a subset of the GAP-43 negative neurons became positive at later stages.
      Such a difference in the expression of GAP-43 protein may contribute to the
      precise patterning of the neural circuits in the mesencephalon in the subsequent
      development. The earliest neurons in the telencephalon, which belong to the
      terminal nerve (TN), were also GAP-43 positive. Since the development of TN is
      poorly understood compared to other cranial nerves, GAP-43 could help the
      detailed analysis of the development of TN as the marker. 

PMID- 24305466
TI  - Observed thinning of Totten Glacier is linked to coastal polynya variability.
AB  - Analysis of ICESat-1 data (2003-2008) shows significant surface lowering of
      Totten Glacier, the glacier discharging the largest volume of ice in East
      Antarctica, and less change on nearby Moscow University Glacier. After accounting
      for firn compaction anomalies, the thinning appears to coincide with fast-flowing
      ice indicating a dynamical origin. Here, to elucidate these observations, we
      apply high-resolution ice-ocean modelling. Totten Ice Shelf is simulated to have
      higher, more variable basal melting rates. We link this variability to the volume
      of cold water, originating in polynyas upon sea ice formation, reaching the sub
      ice-shelf cavity. Hence, we propose that the observed increased thinning of
      Totten Glacier is due to enhanced basal melting caused by a decrease in cold
      polynya water reaching its cavity. We support this hypothesis with passive
      microwave data of polynya extent variability. Considering the widespread changes
      in sea ice conditions, this mechanism could be contributing extensively to ice
      shelf instability. 

PMID- 24305467
TI  - Status quo of annotation of human disease variants.
AB  - BACKGROUND: The ever on-going technical developments in Next Generation
      Sequencing have led to an increase in detected disease related mutations. Many
      bioinformatics approaches exist to analyse these variants, and of those the
      methods that use 3D structure information generally outperform those that do not
      use this information. 3D structure information today is available for about
      twenty percent of the human exome, and homology modelling can double that
      fraction. This percentage is rapidly increasing so that we can expect to analyse
      the majority of all human exome variants in the near future using protein
      structure information. RESULTS: We collected a test dataset of well-described
      mutations in proteins for which 3D-structure information is available. This test
      dataset was used to analyse the possibilities and the limitations of methods
      based on sequence information alone, hybrid methods, machine learning based
      methods, and structure based methods. CONCLUSIONS: Our analysis shows that the
      use of structural features improves the classification of mutations. This study
      suggests strategies for future analyses of disease causing mutations, and it
      suggests which bioinformatics approaches should be developed to make progress in
      this field.

PMID- 24305468
TI  - Lower serum potassium combined with lower sodium concentrations predict long-term
      mortality risk in hemodialysis patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the combined effect of
      different pre-hemodialysis (HD) serum sodium (S[Na]) and potassium (S[K])
      concentrations on the long-term prognosis of HD patients. METHODS: A cohort of
      424 maintenance HD patients (age: 58 +/- 13 years, male: 47%, diabetes: 39%) from
      a single center were divided into four groups based on both medians of S[Na]
      (138.4 mmol/L) and S[K] (4.4 mmol/L): Group 1: lower S[Na] & lower S[K]: n = 92;
      Group 2: lower S[Na] & higher S[K]: n =113; Group 3: higher S[Na] & lower S[K]: n
      =123; Group 4: higher S[Na] & higher S[K]: n =96. The median observation period
      was 21 months. RESULT: By multivariate logistic regression analysis, Group 1 was
      characterized by hypoalbuminemia (OR = 0.37, 95%CI = 0.20-0.67), and lower
      normalized protein catabolism rate (nPCR) (OR = 0.37, 95% CI = 0.16-0.83). In
      contrast, Group 4 was characterized by higher nPCR (OR = 2.26, 95% CI = 1.05
      4.86) and albumin level (OR = 2.26, 95% CI = 1.17-4.39). As compared to the
      reference (group 1), the HR for long-term mortality was significantly lower in
      Groups 3 (HR = 0.54, 95% CI = 0.34- 0.86) and 4 (HR = 0.49, 95% CI = 0.28-0.84).
      By multivariate Cox proportional analysis, Group 1 was an independent factor (HR
      = 1.74, 95% CI = 1.18-2.58) associated with long-term mortality. CONCLUSION: HD
      patients combined with lower S[K] and lower S[Na] were characterized by
      hypoalbuminemia, lower nPCR and a high prevalence of co-morbidity. They were
      associated with long-term mortality risk. On the other hand, those patients with
      higher levels of S[Na] and S[K] tended to have better clinical outcomes.

PMID- 24305469
TI  - Lack of phospholipase A2 receptor increases susceptibility to cardiac rupture
      after myocardial infarction.
AB  - RATIONALE: Recent evidence indicates that the biological effects of secretory
      phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A
      cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity
      ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the
      infarcted myocardium. OBJECTIVE: This study asked whether PLA2R might play a
      pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R(-/
      )). METHODS AND RESULTS: MI was induced by permanent ligation of the left
      coronary artery. PLA2R(-/-) mice exhibited higher rates of cardiac rupture after
      MI compared with PLA2R wild-type (PLA2R(+/+)) mice (46% versus 21%, respectively;
      P=0.015). PLA2R(-/-) mice had a 31% decrease in collagen content and a 45%
      decrease in the number of alpha-smooth muscle actin-positive fibroblasts in the
      infarcted region compared with PLA2R(+/+) mice. PLA2R was primarily found in
      myofibroblasts in the infarcted region. PLA2R(-/-) myofibroblasts were impaired
      in collagen-dependent migration, proliferation, and activation of focal adhesion
      kinase in response to sPLA2-IB. Binding of sPLA2-IB to PLA2R promoted migration
      and proliferation of myofibroblasts through functional interaction with integrin
      beta1, independent of the catalytic activity of sPLA2-IB. In rescue experiments,
      the injection of PLA2R(+/+) myofibroblasts into the infarcted myocardium
      prevented post-MI cardiac rupture and reversed the decrease in collagen content
      in the infarcted region in PLA2R(-/-) mice. CONCLUSIONS: PLA2R deficiency
      increased the susceptibility to post-MI cardiac rupture through impaired healing
      of the infarcted region. This might be partly explained by a reduction in
      integrin beta1-mediated migratory and proliferative responses of PLA2R(-/-)
      myofibroblasts.

PMID- 24305470
TI  - Clinical evaluation of alfaxalone to induce and maintain anaesthesia in cats
      undergoing neutering procedures.
AB  - This study looked at the use and efficacy of alfaxalone for total intravenous
      anaesthesia (TIVA) in cats. Following intramuscular medetomidine (20 MUg/kg) and
      morphine (0.3 mg/kg) premedication, anaesthesia was induced and maintained with
      intravenous alfaxalone. Patients were breathing 100% oxygen. Heart rate (HR),
      respiratory rate (RR), end-tidal carbon dioxide, oxygen saturation of haemoglobin
      and indirect arterial blood pressure via Doppler (DAP) were recorded every 5
      mins. Thirty-four cats (10 males and 24 females), between the age of 6 and 18
      months, and weighing between 1.8 and 5.3 kg, and undergoing neutering procedures
      were included in this study. The results are presented as median (min, max)
      values. The time to first spontaneous movement (TS) was >30 mins in 19 cats, of
      which 12 received atipamezole for reversal of the effects of medetomidine. The TS
      was 53 (43, 130) mins in these 12 cats and 50 (40, 72) mins in the other seven
      cats. The body temperature in those 19 cats was significantly lower than the
      other cats (P = 0.05). The alfaxalone induction dose and maintenance infusion
      rate were1.7 (0.7, 3.0) mg/kg and 0.18 (0.06, 0.25) mg/kg/min, respectively. The
      HR, RR and DAP were 145 (68, 235) beats/min, 17 (5, 40) breaths/min and 110 (58,
      210) mmHg, respectively. Apnoea was not observed in any cat. In conclusion,
      alfaxalone TIVA in combination with medetomidine and morphine premedication was
      effective in feral and domestic cats for the performance of neutering surgery;
      low body temperature might have resulted in longer recoveries in some cats. 

PMID- 24305471
TI  - Indwelling double pigtail ureteral stent combined or not with surgery for feline
      ureterolithiasis: complications and outcome in 15 cases.
AB  - Ureteral obstruction secondary to ureterolithiasis in cats is a challenging
      situation. Ureteral stenting has recently been introduced to prevent
      complications that often occurred after ureterotomy or other invasive surgeries.
      The purpose of this study is to describe the stenting technique and perioperative
      difficulties, as well as long-term outcome and complications with ureteral
      stenting in 12 cats with ureteroliths. Fifteen 2.5 Fr soft double pigtail multi
      fenestrated ureteral stents were placed in an anterograde fashion under open
      surgical approaches and with fluoroscopic guidance in 12 cats. Nine cats received
      a unilateral stent and three received bilateral stents. Ureterotomy or ureteral
      resection and end-to-end anastomosis were performed in three and four cases,
      respectively. In six cats, papillotomy was performed to facilitate dilatator and
      stent placement. All cats recovered well from the surgical procedure, except one
      cat, which died during the anaesthesia recovery period. Postoperative
      complications included dysuria (three cases, diagnosed at 15 days, 1 month and 3
      months, respectively), urinary tract infection (one case, 1 month after surgery),
      stent migration requiring stent replacement (one case, 19 months after surgery)
      and stent obstruction requiring stent removal (three cases with previously end-to
      end anastomosis between 2 and 8 months after surgery). Nine cats (75%) were alive
      at a mean follow-up of 453 +/- 194 (123-720) days. The median survival time was
      >415 days. Stent placement appeared to be a valuable and safe option for treating
      ureteral obstruction in cats. However, periodic and long-term monitoring of
      stents is warranted. 

PMID- 24305473
TI  - Mitochondrial dysfunction in the pathophysiology of renal diseases.
AB  - Mitochondrial dysfunction has gained recognition as a contributing factor in many
      diseases. The kidney is a kind of organ with high energy demand, rich in
      mitochondria. As such, mitochondrial dysfunction in the kidney plays a critical
      role in the pathogenesis of kidney diseases. Despite the recognized importance
      mitochondria play in the pathogenesis of the diseases, there is limited
      understanding of various aspects of mitochondrial biology. This review examines
      the physiology and pathophysiology of mitochondria. It begins by discussing
      mitochondrial structure, mitochondrial DNA, mitochondrial reactive oxygen species
      production, mitochondrial dynamics, and mitophagy, before turning to inherited
      mitochondrial cytopathies in kidneys (inherited or sporadic mitochondrial DNA or
      nuclear DNA mutations in genes that affect mitochondrial function). Glomerular
      diseases, tubular defects, and other renal diseases are then discussed. Next,
      acquired mitochondrial dysfunction in kidney diseases is discussed, emphasizing
      the role of mitochondrial dysfunction in the pathogenesis of chronic kidney
      disease and acute kidney injury, as their prevalence is increasing. Finally, it
      summarizes the possible beneficial effects of mitochondrial-targeted therapeutic
      agents for treatment of mitochondrial dysfunction-mediated kidney injury-genetic
      therapies, antioxidants, thiazolidinediones, sirtuins, and resveratrol-as
      mitochondrial-based drugs may offer potential treatments for renal diseases. 

PMID- 24305472
TI  - Tolvaptan as a tool in renal physiology.
AB  - For decades, the Brattleboro rat has been a useful model in kidney physiology.
      These animals manifest central diabetes insipidus (lack of circulating
      vasopressin) due to a mutation in the vasopressin-neurophysin gene. V2 receptor
      mediated vasopressin actions in the kidney can be assessed in these animals by
      infusing the V2-selective vasopressin analog 1-desamino-8-D-arginine vasopressin
      (dDAVP). However, the major commercial supplier in the United States has ceased
      production, creating the need for another reliable experimental model of V2
      receptor-mediated vasopressin action in rodents. We designed an in vivo protocol
      to investigate vasopressin responses in the rat kidney using osmotic minipumps
      loaded with tolvaptan, a nonpeptide competitive inhibitor of the vasopressin V2
      receptor. Tolvaptan-infused rats had a mean urinary osmolality of <300 vs. >2,000
      mosmol/kgH2O in vehicle-infused rats. The tolvaptan infusion produced large
      decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the
      beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that
      were comparable to the differences seen in vehicle-infused vs. vasopressin
      infused Brattleboro rats. Thus we conclude that tolvaptan infusion in rats
      provides an additional model (besides dDAVP-infusion in the Brattleboro rat) for
      the assessment of V2 receptor-mediated vasopressin actions in the kidney. We also
      provide ancillary in vitro data in rat inner-medullary-collecting-duct
      suspensions showing that tolvaptan can block vasopressin's effects on
      phosphorylation of the water channel AQP2 in vitro. Specifically, tolvaptan
      almost completely inhibited the ability of vasopressin to increase AQP2
      phosphorylation at Ser256, Ser264, and Ser269, while strongly inhibiting a
      vasopressin-induced decrease in AQP2 phosphorylation at Ser261.

PMID- 24305474
TI  - Spatial organization of the vascular bundle and the interbundle region: three
      dimensional reconstruction at the inner stripe of the outer medulla in the mouse
      kidney.
AB  - The vascular bundle (VB) is a complex structure that resides in the inner stripe
      of the outer medulla. At present, the tubulovascular spatial organization of the
      VB, which is crucial for the formation of the osmolarity gradient and for solute
      transport, is still under debate. In this study, we used computer-assisted
      digital tracing combined with aquaporin-1 immunohistochemistry to reconstruct all
      tubules and vessels in the VB of the mouse kidney. We found, first, that the
      descending and ascending vasa recta travelled exclusively through the VB. The
      ascending vasa recta received no tributaries (no branches) along their entire
      path in the medulla and were not connected with the capillary plexus in the
      interbundle region. Second, a specific group of the descending vasa recta were
      closely accompanied by the longest ascending vasa recta, which connected only to
      the capillary plexus at the tip of the papilla. Third, the descending thin limbs
      of all short-looped nephrons travelled exclusively through the outer part of the
      VB. The loops of these nephrons (both descending and ascending parts) were
      distributed in a regular pattern based on their length. Finally, the thick
      ascending limbs of all long-looped nephrons were located at the margin of the VB
      (except a few within the VB), which formed a layer separating the VB from the
      interbundle region. In conclusion, our three-dimensional analysis of the VB
      strongly suggest a lateral osmolarity heterogeneity across the inner stripe of
      the outer medulla, which might work as a driving force for water and solute
      transport. 

PMID- 24305475
TI  - Gratitude: a gift of cancer.
AB  - The holiday season is upon us. Many of our patients and their families are
      juggling their cancer and its treatment while much of the world around them is in
      a festive mood. It brings great clarity when we see this juxtaposition in play.
      And yet, the holidays also are a good time to take stock of the gifts experienced
      by those who have cancer and for those of us working with them. 

PMID- 24305476
TI  - Population-based advanced practice nursing: where does oncology fit in?
AB  - A national work group met in 2004 to discuss the future of advanced practice
      nursing. The representatives were nursing education, certification,
      accreditation, and regulation experts, and the goal was to develop a consensus
      model for advanced practice nursing regulation (Nevidjon et al., 2010). As a
      result, a set of recommendations was published in an article that defined a new
      consensus model for advanced practice registered nurse (APRN) regulation (APRN
      Consensus Workgroup, 2008; Goudreau, 2009). The new model included six population
      based focuses of practice (i.e., family and individual across the lifespan, adult
      and gerontology, neonatal, pediatrics, women's health- and gender-related, and
      psychiatric and mental health) (Johnson, Dawson, & Brassard, 2010). A goal of the
      new model was to standardize the licensure, certification, and regulation of
      nurse practitioners into specific focuses. State boards were facing an increasing
      number of requests to recognize nurse practitioner specialties (e.g., organ
      specific, body systems, diseases) (Johnson et al., 2010). The new model helped
      standardize education programs, which may help certifying agencies set up
      curriculum review processes to ensure appropriate credentials for APRNs (Johnson
      et al., 2010). It also supported the mission of nursing to meet future healthcare
      needs of the public and to protect the public (Johnson et al., 2010). Some
      advantages exist to delineating into population-based focuses, but the new model
      leaves out many specialties (e.g., oncology) that encompass the whole person as
      well as concentrate on certain diseases. 

PMID- 24305477
TI  - Creating moments that matter: strategies to combat compassion fatigue.
AB  - Understanding compassion fatigue and devising and implementing interventions to
      address the subject are important for nurses and patients. However, few
      literature reports exist that address interventions for nurses who experience
      compassion fatigue. This article discusses how nurses on a medical-surgical
      oncology unit in an academic, community MagnetTM hospital adopted these themes as
      a conceptual framework on which to focus actions to avoid and mitigate compassion
      fatigue. 

PMID- 24305478
TI  - Improving practice one patient, one nurse, one day at a time: design and
      evaluation of a quality education workshop for oncology nurses.
AB  - High-quality nursing care is not delivered consistently to the millions of
      Americans treated for invasive cancer in the United States. As part of its
      quality initiative, the Oncology Nursing Society (ONS) developed and tested
      nursing-sensitive quality measures for breast cancer care. Findings from the
      pilot testing suggested significant knowledge and practice gaps that could be
      addressed through member education. 

PMID- 24305479
TI  - Catheter-associated urinary tract infection prevention in the oncology
      population: an evidence-based approach.
AB  - Urinary catheters have been attributed to almost half of all healthcare
      associated infections. Many catheter-associated urinary tract infections (CAUTIs)
      may be prevented by following recommended guidelines, which would save lives.
      This article illustrates the use of known guidelines for the prevention of CAUTIs
      in the oncology population. 

PMID- 24305480
TI  - The science of patient safety: implications for oncology nursing practice.
AB  - Patient safety is one of the most frequent terms used in health care today.
      Patients and their families are, first and foremost, focused on receiving
      effective and safe care, and oncology nurses strive to incorporate clinical
      evidence into day-to-day practice. This article provides a road map on how to
      incorporate emerging patient safety science into daily clinical practice to best
      serve patients and their families. 

PMID- 24305481
TI  - Monoclonal gammopathy of undetermined significance-making it understandable to
      patients.
AB  - Oncology nurses working in ambulatory care often encounter patients with
      nonmalignant hematologic disorders because the specialties of hematology and
      oncology are closely entwined. A variety of nonmalignant hematologic disorders
      can evolve into blood malignancies; therefore, close surveillance of nonmalignant
      hematologic disorders in an oncology/hematology clinic is important for early
      detection of malignancy. Monoclonal gammopathy of undetermined significance
      (MGUS) is one nonmalignant, hematologic disorder that is usually aproblematic;
      however, it can evolve into a blood malignancy such as multiple myeloma or be
      associated with other chronic conditions. This article provides an overview of
      MGUS with a focus on implications for the oncology nurse and patient education. 

PMID- 24305482
TI  - Ocular graft-versus-host disease after allogeneic transplantation.
AB  - Ocular graft-versus-host disease (GVHD) is a common complication that occurs
      after allogeneic transplantation. It can cause severe dry eyes that are described
      as having a burning, gritty, and painful sensation. Ocular GVHD can affect
      quality of life by causing pain and photophobia, limiting activities of daily
      living (e.g., reading, watching television), compromising safety while driving,
      and permanently damaging vision. Pre- and post-transplantation evaluations by an
      ophthalmologist are recommended. Routine assessments using the National
      Institutes of Health eye score should be administered to patients at each follow
      up visit to their transplantation physician. Treatment options include
      lubricating eye drops, immunomodulator and steroid drops, and punctal occlusion.
      Relieving symptoms is difficult, and although multiple treatment options exist,
      many are ineffective. The Boston Foundation for Sight's scleral lens is an
      available option that promotes corneal healing and symptom relief. The current
      article discusses treatment options and supportive care measures for patients
      with ocular GVHD aimed at relieving symptoms and preventing complications. 

PMID- 24305483
TI  - Identifying strategies to optimize care with oral cancer therapy.
AB  - More cancer therapies are being administered via an oral route. This paradigm
      shift in providing cancer treatment has been met with both excitement and
      significant challenges for oncology practitioners. Multiple factors can impact
      the ability for patients to initiate and stay on oral cancer therapy. A major
      factor in patient adherence with oral cancer therapies is management of side
      effects. Side effects from therapy not only have a negative impact on a patient's
      quality of life but also can cause serious complications. In addition, they can
      impact the patient's ability to stay on therapy at optimal doses. New strategies
      must be designed for educating patients and caregivers, as well as for patient
      management and follow-up. When side effects are not managed appropriately,
      patients are less likely to want or be able to adhere to established treatment
      plans. This article explores several challenges related to the use of oral cancer
      therapies, with a focus on side effects seen with various classes of new targeted
      agents. Evidence-based practice strategies and areas in need of additional
      exploration and research are reviewed. 

PMID- 24305484
TI  - End-of-life decision making in hematopoietic cell transplantation recipients.
AB  - Discussions about futile treatment options for patients undergoing hematopoietic
      cell transplantation (HCT) can be difficult for healthcare providers. These
      discussions often are not initiated before transplantation, but only after a
      patient's healthcare status deteriorates. Nurses are in a key position to provide
      support and advocate for patients and their families in end-of-life (EOL)
      decisions. A need exists for increased autonomy for nurses as patient advocates.
      Implementation of multidisciplinary nursing education, both in schools and in the
      workplace, will support these new responsibilities. This article will provide a
      review of the literature related to the nurse role in the transition from active
      treatment (aggressive care) to EOL care in the HCT population. 

PMID- 24305485
TI  - Care of the body after death.
AB  - Care of the body after death is an important nursing function that occurs in a
      wide variety of contexts. After a patient dies, nursing care continues as
      physical care of the body as well as care of the family members. In this
      descriptive, qualitative study, the authors explored nurse perceptions of what it
      means to care for the body after death. Narratives describing this care were
      collected and analyzed. The descriptions were coded and two overarching themes
      emerged: giving respectful and dignified after-death care (ADC) that is sensitive
      to the needs of the family and ADC providing nurses with a mechanism for coping
      with care of dying patients. To ensure patient and family ADC needs are not
      superseded by nurses' own coping needs, comprehensive patient and family-centered
      ADC planning is recommend. Grief resolution opportunities, end-of-life education,
      and mentoring should be available to support nurses with post-death experiences. 

PMID- 24305486
TI  - The benefits of medical qigong in patients with cancer: a descriptive pilot
      study.
AB  - Medical Qigong (MQ) is a mind-body exercise that includes movement and meditation
      and is beneficial in reducing high blood pressure, high cholesterol, anxiety,
      stress, pain, and incidence of falls. The purpose of the current study was to
      determine whether patients with cancer and survivors who participated in an MQ
      class experienced a change in fatigue, depression, and sleep from a
      preintervention evaluation to a postintervention evaluation. Participants were
      patients diagnosed with cancer who participated in MQ classes. Some were actively
      undergoing cancer treatment (e.g., surgery, hormone therapy, radiation therapy,
      chemotherapy) and some were receiving no treatment. Patients diagnosed with
      cancer and enrolled in an MQ class were invited to participate. A packet of
      surveys was completed before the first class and before the final class. Scores
      showed a reduced depression score after completing the five-week MQ course. Those
      findings indicate that MQ is helpful in reducing some of the problems associated
      with cancer and cancer treatment. 

PMID- 24305487
TI  - Head and neck cancer: historical evolution of treatment and patient self-care
      requirements.
AB  - The purpose of this literature review is to explore the historical progression of
      treatment and its impact on care requisites in patients with head and neck
      cancer. Head and neck cancers are some of the most visible types of cancer.
      Patients often experience difficulties in self-care because of problems adapting
      to and coping with the diagnosis and disease management. Evaluation of the
      literature from the 1960s to present indicated a shift from coping with
      disfigurement to focusing on dysfunction and rehabilitative self-care. The
      process of assisting patients with self-care activities occurs from the time of
      diagnosis through post-treatment and beyond. Adapting to and coping with changes
      in physical appearance and function begins with the cognitive decision to
      initiate treatment modalities specific to the cancer site. Current knowledge of
      the manifestations of head and neck cancer provides the healthcare team with a
      better understanding of the disease trajectory and how best to assist patients in
      adapting to and coping with changes affecting their quality of life. 

PMID- 24305488
TI  - Diagnosis, treatment, and management of immune thrombocytopenia.
AB  - Management of immune thrombocytopenia (ITP) requires accurate assessment and
      evaluation, appropriate treatment strategies, and timely nursing interventions
      (e.g., monitoring, bleeding prevention, patient education). The overview of ITP
      in the current article reviews its etiology and provides updates about medical
      management and key components of nursing care. 

PMID- 24305489
TI  - Tumor cell dissemination secondary to surgical interventions in the breast.
AB  - Dissemination secondary to surgical interventions is an issue that arises in
      conversations between patients and providers prior to breast biopsy. Research
      supports needle biopsies over incisional or excisional biopsies in most
      situations. Tumor cell dissemination is a rare occurrence. However, the fear of
      dissemination as experienced by the patient is very real. That fear may influence
      the patient's decision to proceed with a recommended biopsy. 

PMID- 24305490
TI  - Enhancing patient outcomes in healthcare systems through multidisciplinary
      teamwork.
AB  - The increasingly complex needs of patients with cancer and their families call
      for a multidisciplinary team to achieve optimal patient outcomes. The purpose of
      the current article is to describe a teamwork model that can be used to address
      the needs of patients and the challenges associated with a healthcare system. The
      teamwork model was developed to address the mechanism needed to establish a
      paradigm shift in achieving high-quality patient care through effective teamwork.

PMID- 24305491
TI  - Dietary flavonoids for the prevention of colorectal cancer.
AB  - To assess whether dietary flavonoids have an effect on the incidence of
      colorectal adenoma and colorectal cancer. 

PMID- 24305492
TI  - The pathway to becoming a professional nurse.

PMID- 24305493
TI  - Who am I? Reflections on self-image among patients with cancer in clinical
      trials.
AB  - Patients with cancer who participate in research face difficult challenges. Their
      lives change in many ways, and they often question their self-image. Self-image
      includes how patients see themselves and who they want to become. The current
      commentary addresses the issue of self-image in patients with cancer who
      participate in clinical trials and how their sense of who they were changes as
      they shift from patients with cancer to research participants. Patients with
      cancer who participate in research may suffer from multiple identity transitions,
      ranging from physical alterations in appearance and bodily capabilities to
      psychological burdens of job loss and the inability to contribute financially to
      their families. The author aims to provide insight as to how researchers can help
      patients find meaning in their lives during the process of participation in
      clinical trials as they undergo identity transitions. 

PMID- 24305494
TI  - Resources for physical activity in cancer centers in the United States.
AB  - Physical activity (PA) has many benefits for cancer survivors. However, the
      available PA resources for survivors at cancer centers throughout the United
      States are undocumented. The current study surveyed major cancer centers
      concerning the availability and types (e.g., facilities, programs, counseling,
      information resources) of PA resources available. Of supportive care services, PA
      resources were the least commonly reported. Significant correlations were found
      among availability of PA resources and other supportive care services. Although
      many cancer centers reported offering PA programming, formal and informal PA
      guidance and support seem to fall on oncology nurses and other clinicians.
      Oncology nurses should be reminded that they may be one of the only sources of PA
      guidance available to survivors at cancer centers. 

PMID- 24305495
TI  - Children and adolescents deaths from trauma-related causes in a Brazilian City.
AB  - INTRODUCTION: Injury is the first cause of death worldwide in the population aged
      1 to 44. In developed countries, the most common trauma-related injuries
      resulting in death during childhood are traffic accidents, followed by drowning.
      METHODS: This retrospective study based on autopsy examinations describes the
      epidemiology profile of deaths by trauma-related causes in individuals younger
      than 18 years from 2001 to 2008 in the city of Campinas. The aim is to identify
      epidemiology changes throughout the years in order to develop strategies of
      prevention. RESULTS: There were 2,170 deaths from all causes in children < 18
      years old, 530 of which were due to trauma-related causes, with a male
      predominance of 3.4:1. The age distribution revealed that 76% of deaths occurred
      in the 10-17 age group. The most predominant trauma cause was firearm injury
      (47%). Other frequent causes were transport-related injuries (138 cases-26%;
      pedestrians were struck in 57.2% of these cases) and drowning (55 cases-10.4%).
      Asphyxia/suffocation was the cause of death in 72% of cases in children < 1 year
      old; drowning (30.8%) was predominant in the 1-4 age group; transport-related
      deaths were frequent in the 5-9 age group (56%) and the 10-14 age group (40.4%).
      Gun-related deaths were predominant (68%) in the 14-17 age group. 51% of deaths
      occurred at the scene. CONCLUSIONS: There was a predominance of deaths in
      children and adolescents males, between 15-17 years old, mainly from gun-related
      homicides, and the frequency has decreased since 2004 after the disarmament
      statute and the combating of violence.

PMID- 24305496
TI  - Equation of state of zircon- and scheelite-type dysprosium orthovanadates: a
      combined experimental and theoretical study.
AB  - Dysprosium orthovanadate, DyVO4, belongs to a family of zircon-type
      orthovanadates showing a phase transition to scheelite-type structures at
      moderate pressures below 10 GPa. In the present study, the equations of state
      (EOSs) for both these phases were determined for the first time using high
      pressure x-ray diffraction experiments and ab initio calculations based on the
      density functional theory. Structural parameters for scheelite-type DyVO4 were
      calculated from x-ray powder diffraction data as well. The high-pressure
      experiments were performed under pseudo-hydrostatic conditions at pressures up to
      8.44 GPa and 5.5 GPa for the stable zircon-type and metastable (quenched)
      scheelite-type samples, respectively. Assuming as a compression model the Birch
      Murnaghan EOS, we obtained the EOS parameters for both phases. The experimental
      bulk moduli (K0) for zircon-type and scheelite-type DyVO4 are 118(4) GPa and
      153(6) GPa, respectively. Theoretical equations of state were determined by ab
      initio calculations using the PBE exchange-correlation energy functional of
      Perdew, Burke, and Ernzerhof. These calculations provide K0 values of 126.1 GPa
      and 142.9 GPa for zircon-type and scheelite-type DyVO4, respectively. The
      reliability of the present experimental and theoretical results is supported by
      (i) the consistency between the values yielded by the two methods (the
      discrepancy in K0 is as low as about 7% for each of the studied polymorphs) and
      (ii) their similarity to results obtained under similar compression conditions
      (hydrostatic or pseudo-hydrostatic) for other rare-earth orthovanadates, such as
      YVO4 and TbVO4.

PMID- 24305497
TI  - The journal--new for 2014.

PMID- 24305499
TI  - Increased levels of plasma p3-alcalpha35, a major fragment of Alcadeinalpha by
      gamma-secretase cleavage, in Alzheimer's disease.
AB  - p3-Alcalpha is a metabolic fragment of Alcadeinalpha (Alcalpha). Similar to the
      generation of the p3 fragment from amyloid-beta protein precursor (AbetaPP)
      processing, Alcalpha is cleaved by alpha- and gamma-secretases, leading to the
      secretion of p3-Alcalpha peptides into cerebrospinal fluid (CSF). p3-Alcalpha is
      also detected in the plasma, similar to amyloid-beta (Abeta), which is a
      metabolic fragment of AbetaPP cleaved by amyloidogenic beta- and gamma
      secretases. Because p3-Alcalpha is a non-aggregatable and stable peptide, unlike
      aggregatable Abeta and metabolically labile p3 of AbetaPP, the changes of p3
      Alcalpha in quality and/or quantity in CSF and plasma are expected to be a marker
      for assessing alteration of substrate cleavage by gamma-secretase, such as Abeta
      generation from AbetaPP. The present study describes a sandwich enzyme-linked
      immunosorbent assay for quantifying levels of p3-Alcalpha35, the major form of
      the p3-Alcalpha species, and examines levels of p3-Alcalpha35 in the plasma of
      three independent Japanese cohorts. In two of the three cohorts, the p3
      Alcalpha35 levels were significantly increased with a concomitant decrease in the
      Mini-Mental State Examination score, or in clinically diagnosed Alzheimer's
      disease (AD) patients, when compared with age-matched non-demented subjects. The
      values were significantly lower in AD subjects who were administered donepezil,
      when compared to AD subjects without donepezil treatment. The increase in plasma
      p3-Alcalpha35 levels may indicate an endophenotype in subjects in whom AD is due
      to a progressing cognitive impairment in subjects with a gamma-secretase
      malfunction, or a disorder of the clearance of peptides.

PMID- 24305500
TI  - Abeta38 in the brains of patients with sporadic and familial Alzheimer's disease
      and transgenic mouse models.
AB  - The pathogenesis of Alzheimer's disease (AD) is believed to be closely dependent
      on deposits of neurotoxic amyloid-beta peptides (Abeta), which become abundantly
      present throughout the central nervous system in advanced stages of the disease.
      The different Abeta peptides existing are generated by subsequent cleavage of the
      amyloid-beta protein precursor (AbetaPP) and may vary in length and differ at
      their C-terminus. Despite extensive studies on the most prevalent species Abeta40
      and Abeta42, Abeta peptides with other C-termini such as Abeta38 have not
      received much attention. In the present study, we used a highly specific and
      sensitive antibody against Abeta38 to analyze the distribution of this Abeta
      species in cases of sporadic and familial AD, as well as in the brains of a
      series of established transgenic AD mouse models. We found Abeta38 to be present
      as vascular deposits in the brains of the majority of sporadic AD cases, whereas
      it is largely absent in non-demented control cases. Abeta38-positive
      extracellular plaques were virtually limited to familial cases. Interestingly we
      observed Abeta38-positive plaques not only among familial cases due to AbetaPP
      mutations, but also in cases of familial AD caused by presenilin (PSEN)
      mutations. Furthermore we demonstrate that Abeta38 deposits in the form of
      extracellular plaques are common in several AD transgenic mouse models carrying
      either only AbetaPP, or combinations of AbetaPP, PSEN1, and tau transgenes.

PMID- 24305502
TI  - Weighing up non-clinical factors when choosing drugs.

PMID- 24305501
TI  - Combined administration of testosterone plus an ornithine decarboxylase inhibitor
      as a selective prostate-sparing anabolic therapy.
AB  - Because of its anabolic effects on muscle, testosterone is being explored as a
      function-promoting anabolic therapy for functional limitations associated with
      aging; however, concerns about testosterone's adverse effects on prostate have
      inspired efforts to develop strategies that selectively increase muscle mass
      while sparing the prostate. Testosterone's promyogenic effects are mediated
      through upregulation of follistatin. We show here that the administration of
      recombinant follistatin (rFst) increased muscle mass in mice, but had no effect
      on prostate mass. Consistent with the results of rFst administration, follistatin
      transgenic mice with constitutively elevated follistatin levels displayed greater
      muscle mass than controls, but had similar prostate weights. To elucidate
      signaling pathways regulated differentially by testosterone and rFst in prostate
      and muscle, we performed microarray analysis of mRNAs from prostate and levator
      ani of castrated male mice treated with vehicle, testosterone, or rFst.
      Testosterone and rFst shared the regulation of many transcripts in levator ani;
      however, in prostate, 593 transcripts in several growth-promoting pathways were
      differentially expressed after testosterone treatment, while rFst showed a
      negligible effect with only 9 transcripts differentially expressed. Among
      pathways that were differentially responsive to testosterone in prostate, we
      identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis,
      as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we
      administered testosterone with and without alpha-difluoromethylornithine (DFMO),
      an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone's
      effects on prostate, but did not affect testosterone's anabolic effects on
      muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel
      therapeutic strategy for prostate-sparing anabolic therapy. 

PMID- 24305503
TI  - Measuring memory with the order of fractional derivative.
AB  - Fractional derivative has a history as long as that of classical calculus, but it
      is much less popular than it should be. What is the physical meaning of
      fractional derivative? This is still an open problem. In modeling various memory
      phenomena, we observe that a memory process usually consists of two stages. One
      is short with permanent retention, and the other is governed by a simple model of
      fractional derivative. With the numerical least square method, we show that the
      fractional model perfectly fits the test data of memory phenomena in different
      disciplines, not only in mechanics, but also in biology and psychology. Based on
      this model, we find that a physical meaning of the fractional order is an index
      of memory. 

PMID- 24305504
TI  - International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group:
      proposed diagnostic criteria for chronic GVHD (Part I).
AB  - The International Chronic Ocular GVHD Consensus Group held 4 working meetings to
      define new diagnostic metrics for chronic ocular graft-versus-host disease
      (GVHD). After considering the factors currently used to diagnose chronic ocular
      GVHD, the Consensus Group identified 4 subjective and objective variables to
      measure in patients following allogeneic hematopoietic stem cell transplantation
      (HSCT): OSDI, Schirmer's score without anesthesia, corneal staining, and
      conjunctival injection. Each variable was scored 0-2 or 0-3, with a maximum
      composite score of 11. Consideration was also given to the presence or the
      absence of systemic GVHD. On the basis of their composite score and the presence
      or absence of systemic GVHD, patients were assigned to one of three diagnostic
      categories: NO, PROBABLE, or DEFINITE ocular GVHD. New diagnostic criteria for
      chronic ocular GVHD are presented by the Consensus Group. Validation studies are
      needed to identify the best combination of the proposed metrics to maximize
      diagnostic sensitivity and specificity. 

PMID- 24305505
TI  - Recent advances in acute lymphoblastic leukemia in children and adolescents: an
      expert panel discussion.
AB  - PURPOSE OF REVIEW: Acute lymphoblastic leukemia (ALL) is the most common form of
      childhood leukemia, representing 75% to 80% of cases of acute leukemia among
      children. Dramatic improvements in the cure rates and survival outcomes for
      children with ALL have been seen over the past several decades; currently the 5
      year survival rate for childhood ALL is more than 80%. These improvements have
      come about because of advances in the understanding of the molecular genetics and
      pathogenesis of the disease, incorporation of risk-adapted therapy, and the
      advent of new targeted agents. RECENT FINDINGS: Scientific advances have provided
      new insights into leukemogenesis, drug resistance, and host pharmacogenomics,
      identified novel subtypes of leukemia, and suggested potential targets for
      therapy. At the same time novel monoclonal antibodies, small molecule inhibitors,
      chemotherapeutics, and cell-based treatment strategies have been developed and
      investigated. SUMMARY: In this article, experts will discuss some of the current
      challenges and future directions in the treatment of pediatric ALL. The authors
      will offer expert guidance to practicing oncologists on how to best incorporate
      newer treatment approaches into the care of children and adolescents with ALL.
      The most important ongoing clinical trials in the area will also be reviewed.

PMID- 24305507
TI  - Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of
      human mantle cell lymphoma.
AB  - BACKGROUND: The chemokine receptor CCR7 mediates lymphoid dissemination of many
      cancers, including lymphomas and epithelial carcinomas, thus representing an
      attractive therapeutic target. Previous results have highlighted the potential of
      the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The
      present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7
      antibody in a xenografted human mantle cell lymphoma model. METHODS: NOD/SCID
      mice were either subcutaneously or intravenously inoculated with Granta-519
      cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti
      CCR7 mAb treatment (3 * 200 MUg) was started on day 2 or 7 to target lymphoma
      cells in either a peri-implantation or a post-implantation stage, respectively.
      RESULTS: The anti-CCR7 therapy significantly delayed the tumor appearance and
      also reduced the volumes of tumors in the subcutaneous model. Moreover, an
      increased number of apoptotic tumor cells was detected in mice treated with the
      anti-CCR7 mAb compared to the untreated animals. In addition, significantly
      reduced number of Granta-519 cells migrated from subcutaneous tumors to distant
      lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In
      the intravenous models, the anti-CCR7 mAb drastically increased survival of the
      mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and
      non-lymphoid organs, including lungs and central nervous system, was almost
      abrogated. CONCLUSIONS: The anti-CCR7 mAb exerts a potent anti-tumor activity and
      might represent an interesting therapeutic alternative to conventional therapies.

PMID- 24305508
TI  - Do patients with type 1 and type 2 diabetes really have an impaired endothelial
      function? A population-based propensity score matching analysis.
AB  - BACKGROUND: Previous studies suggested an impaired endothelial function in
      patients with diabetes. However, the validity of this finding may be limited by
      the lack of adequate adjustment for further cardiovascular confounders. We
      assessed endothelial function as measured by flow-mediated dilation (FMD) of the
      brachial artery in patients with either type 1 or type 2 diabetes in comparison
      with non-diabetic controls. METHODS: The study population comprised 1487 subjects
      including 122 subjects with type 2 diabetes, aged 25 to 85, from the population
      based Study of Health in Pomerania, and 65 outpatients, aged 23 to 75, with type
      1 diabetes. FMD measurements were performed using standardized ultrasound
      techniques. Subjects with type 1 and type 2 diabetes were matched 1:4 to healthy
      controls using propensity score matching. RESULTS: Neither type 1 diabetes (beta
      = 0.142; SE = 0.568, p = 0.803) nor type 2 diabetes (beta = 0.107; SE = 0.340, p
      = 0.752) were significantly associated with FMD in comparison with their non
      diabetic controls after adjustment for major cardiovascular confounders like age,
      gender, body mass index, smoking status, hypertension, antihypertensive
      medication, LDL and HDL cholesterol levels. CONCLUSIONS: In this population-based
      study comparing adjusted FMD values of diabetic individuals with adequately
      matched controls, propensity score analyses revealed no association between
      diabetes and endothelial function. Since these findings are in discordance with
      the majority of previous reports, we suggest performing similar analyses using
      data from other population-based studies.

PMID- 24305509
TI  - Clustering of health-related behaviors, health outcomes and demographics in Dutch
      adolescents: a cross-sectional study.
AB  - BACKGROUND: Recent studies show several health-related behaviors to cluster in
      adolescents. This has important implications for public health. Interrelated
      behaviors have been shown to be most effectively targeted by multimodal
      interventions addressing wider-ranging improvements in lifestyle instead of via
      separate interventions targeting individual behaviors. However, few previous
      studies have taken into account a broad, multi-disciplinary range of health
      related behaviors and connected these behavioral patterns to health-related
      outcomes. This paper presents an analysis of the clustering of a broad range of
      health-related behaviors with relevant demographic factors and several health
      related outcomes in adolescents. METHODS: Self-report questionnaire data were
      collected from a sample of 2,690 Dutch high school adolescents. Behavioral
      patterns were deducted via Principal Components Analysis. Subsequently a Two-Step
      Cluster Analysis was used to identify groups of adolescents with similar
      behavioral patterns and health-related outcomes. RESULTS: Four distinct
      behavioral patterns describe the analyzed individual behaviors: 1- risk-prone
      behavior, 2- bully behavior, 3- problematic screen time use, and 4- sedentary
      behavior. Subsequent cluster analysis identified four clusters of adolescents.
      Multi-problem behavior was associated with problematic physical and psychosocial
      health outcomes, as opposed to those exerting relatively few unhealthy behaviors.
      These associations were relatively independent of demographics such as ethnicity,
      gender and socio-economic status. CONCLUSIONS: The results show that health
      related behaviors tend to cluster, indicating that specific behavioral patterns
      underlie individual health behaviors. In addition, specific patterns of health
      related behaviors were associated with specific health outcomes and demographic
      factors. In general, unhealthy behavior on account of multiple health-related
      behaviors was associated with both poor psychosocial and physical health. These
      findings have significant meaning for future public health programs, which should
      be more tailored with use of such knowledge on behavioral clustering via e.g.
      Transfer Learning.

PMID- 24305510
TI  - Efficient piezoelectric ZnO nanogenerators based on Au-coated silica sphere array
      electrode.
AB  - We reported ZnO nanorod-based piezoelectric nanogenerators (NGs) with Au-coated
      silica sphere array as an efficient top electrode. This electrode can readily
      bend the ZnO nanorods due to its enhanced surface roughness, thus resulting in
      more increased and regular piezoelectric charge output. Under a low external
      pushing force of 0.3 kgf, the output current and voltage were increased by
      approximately 2.01 and 1.51 times, respectively, in comparison with a
      conventional Au top electrode without silica spheres. Also, the effect of Au
      coated silica spheres on the bending radius of ZnO nanorods was theoretically
      investigated. 

PMID- 24305512
TI  - The causal effect of red blood cell folate on genome-wide methylation in cord
      blood: a Mendelian randomization approach.
AB  - BACKGROUND: Investigation of the biological mechanism by which folate acts to
      affect fetal development can inform appraisal of expected benefits and risk
      management. This research is ethically imperative given the ubiquity of folic
      acid fortified products in the US. Considering that folate is an essential
      component in the one-carbon metabolism pathway that provides methyl groups for
      DNA methylation, epigenetic modifications provide a putative molecular mechanism
      mediating the effect of folic acid supplementation on neonatal and pediatric
      outcomes. RESULTS: In this study we use a Mendelian Randomization Unnecessary
      approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA
      methylation in cord blood. Site-specific CpG methylation within the proximal
      promoter regions of approximately 14,500 genes was analyzed using the Illumina
      Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth
      Cohort at Brigham and Women's Hospital in Boston. Using methylenetetrahydrofolate
      reductase genotype as the instrument, the Mendelian Randomization approach
      identified 7 CpG loci with a significant (mostly positive) association between
      RBC folate and methylation level. Among the genes in closest proximity to this
      significant subset of CpG loci, several enriched biologic processes were involved
      in nucleic acid transport and metabolic processing. Compared to the standard
      ordinary least squares regression method, our estimates were demonstrated to be
      more robust to unmeasured confounding. CONCLUSIONS: To the authors' knowledge,
      this is the largest genome-wide analysis of the effects of folate on methylation
      pattern, and the first to employ Mendelian Randomization to assess the effects of
      an exposure on epigenetic modifications. These results can help guide future
      analyses of the causal effects of periconceptional folate levels on candidate
      pathways.

PMID- 24305511
TI  - Essential regulation of cell bioenergetics in Trypanosoma brucei by the
      mitochondrial calcium uniporter.
AB  - Mechanisms of regulation of mitochondrial metabolism in trypanosomes are not
      completely understood. Here we present evidence that the Trypanosoma brucei
      mitochondrial calcium uniporter (TbMCU) is essential for the regulation of
      mitochondrial bioenergetics, autophagy and cell death, even in the bloodstream
      forms that are devoid of a functional respiratory chain and oxidative
      phosphorylation. Localization studies reveal its co-localization with MitoTracker
      staining. TbMCU overexpression increases mitochondrial Ca(2+) accumulation in
      intact and permeabilized trypanosomes, generates excessive mitochondrial reactive
      oxygen species (ROS) and sensitizes them to apoptotic stimuli. Ablation of TbMCU
      in RNAi or conditional knockout trypanosomes reduces mitochondrial Ca(2+) uptake
      without affecting their membrane potential, increases the AMP/ATP ratio,
      stimulates autophagosome formation and produces marked defects in growth in vitro
      and infectivity in mice, revealing its essentiality in these parasites. The
      requirement of TbMCU for proline and pyruvate metabolism in procyclic and
      bloodstream forms, respectively, reveals its role in regulation of mitochondrial
      bioenergetics. 

PMID- 24305513
TI  - Dispersion method for safety research on manufactured nanomaterials.
AB  - Nanomaterials tend to agglomerate in aqueous media, resulting in inaccurate
      safety assessment of the biological response to these substances. The present
      study searched for suitable dispersion methods for the preparation of
      nanomaterial suspensions. Titanium dioxide (TiO2) and zinc oxide (ZnO)
      nanoparticles were dispersed in a biocompatible dispersion medium by direct probe
      type sonicator and indirect cup-type sonicator. Size characterization was
      completed using dynamic light scattering and transmission electron microscopy. A
      series of dispersion time and output power, as well as two different particle
      concentrations were tested. Microscopic contamination of metal titanium that
      broke away from the tip of the probe into the suspension was found. Size of
      agglomerated nanoparticles decreased with increase in sonication time or output
      power. Particle concentration did not show obvious effect on size distribution of
      TiO2 nanoparticles, while significant reduction of secondary diameter of ZnO was
      observed at higher concentration. A practicable protocol was then adopted and
      sizes of well-dispersed nanoparticles increased by less than 10% at 7 d after
      sonication. Multi-walled carbon nanotubes were also well dispersed by the same
      protocol. The cup-type sonicator might be a useful alternative to the traditional
      bath-type sonicator or probe-type sonicator based on its effective energy
      delivery and assurance of suspension purity. 

PMID- 24305514
TI  - Text messaging data collection for monitoring an infant feeding intervention
      program in rural China: feasibility study.
AB  - BACKGROUND: An effective data collection method is crucial for high quality
      monitoring of health interventions. The traditional face-to-face data collection
      method is labor intensive, expensive, and time consuming. With the rapid increase
      of mobile phone subscribers, text messaging has the potential to be used for
      evaluation of population health interventions in rural China. OBJECTIVE: The
      objective of this study was to explore the feasibility of using text messaging as
      a data collection tool to monitor an infant feeding intervention program.
      METHODS: Participants were caregivers of children aged 0 to 23 months in rural
      China who participated in an infant feeding health education program. We used the
      test-retest method. First, we collected data with a text messaging survey and
      then with a face-to-face survey for 2 periods of 3 days. We compared the response
      rate, data agreement, costs, and participants' acceptability of the two methods.
      Also, we interviewed participants to explore their reasons for not responding to
      the text messages and the reasons for disagreement in the two methods. In
      addition, we evaluated the most appropriate time during the day for sending text
      messages. RESULTS: We included 258 participants; 99 (38.4%) participated in the
      text messaging survey and 177 (68.6%) in the face-to-face survey. Compared with
      the face-to-face survey, the text messaging survey had much lower response rates
      to at least one question (38.4% vs 68.6%) and to all 7 questions (27.9% vs 67.4%)
      with moderate data agreement (most kappa values between .5 and .75, the
      intraclass correlation coefficients between .53 to .72). Participants who took
      part in both surveys gave the same acceptability rating for both methods (median
      4.0 for both on a 5-point scale, 1=disliked very much and 5=liked very much). The
      costs per questionnaire for the text messaging method were much lower than the
      costs for the face-to-face method: Y19.7 (US $3.13) versus Y33.9 (US $5.39) for
      all questionnaires, and Y27.1 (US $4.31) versus Y34.4 (US $5.47) for completed
      questionnaires. The main reasons for not replying were that participants did not
      receive text messages, they were too busy to reply, or they did not see text
      messages in time. The main reasons for disagreement in responses were that
      participants forgot their answers in the text messaging survey and that they
      changed their minds. We found that participants were more likely to reply to text
      messages immediately during 2 time periods: 8 AM to 3 PM and 8 PM to 9 PM.
      CONCLUSIONS: The text messaging method had reasonable data agreement and low
      cost, but a low response rate. Further research is needed to evaluate
      effectiveness of measures that can increase the response rate, especially in
      collecting longitudinal data by text messaging.

PMID- 24305516
TI  - A stable, quasi-2D modification of silver: optical, electronic, vibrational and
      mechanical properties, and first principles calculations.
AB  - We report the optical, electronic, vibrational and mechanical properties of a
      stable, anisotropic, hexagonal (4H) form of silver. First principles calculations
      based on density functional theory were used to simulate the phonon dispersion
      curves and electronic band structure of 4H-Ag. The phonon dispersion data at 0 K
      do not contain unstable phonon modes, thereby confirming that it is a locally
      stable structure. The Fermi surface of the 4H phase differs in a subtle way from
      that of the cubic phase. Experimental measurements indicate that, when compared
      to the commonly known face-centered cubic (3C) form of silver, the 4H-Ag form
      shows a 130-fold higher, strongly anisotropic, in-plane resistivity and a much
      lower optical reflectance with a pronounced surface plasmon contribution that
      imparts a distinctive golden hue to the material. Unlike common silver, the lower
      symmetry of the 4H-Ag structure allows it to be Raman active. Mechanically, 4H-Ag
      is harder, more brittle and less malleable. Overall, this novel, poorly metallic,
      anisotropic, darker and harder crystallographic modification of silver bears
      little resemblance to its conventional counterpart.

PMID- 24305515
TI  - Integrated FDG-PET/CT imaging is useful in the approach to carcinoid tumors of
      the lung.
AB  - BACKGROUND: Carcinoids enter the differential diagnosis of the solitary pulmonary
      nodule. Bronchial carcinoids have been traditionally considered as FDG-PET
      negative but recent studies have found an higher sensitivity of integrated FDG
      PET/CT for the detection of these neoplasms. The purpose of this study was to
      investigate the value of integrated FDG-PET/CT for the evaluation of SPN
      suspected to be carcinoids. METHODS: All patients with pathologically proven
      bronchial carcinoids who had FDG-PET/CT scans between 2006 and 2012 have been
      retrospectively reviewed. PET/CT was performed with the same scanner and the same
      technique for all patients. The following data were retrieved: age, sex CT
      findings (side, location, size, shape, margins), SUVmax, type of operation,
      pathological findings (size and number of mitoses). Regarding PET findings, only
      SUVmax was considered, whereas the visual assessment was not undertaken.
      Carcinoids were defined as typical and atypical and as central and peripheral.
      The long-term follow-up was also recorded. The SUVmax was compared with the other
      clinical, radiological and pathological variables to find any significant
      difference or correlation. RESULTS: Twenty-five patients were retrieved, 24
      typical and one atypical carcinoid, 21 peripheral and 4 central lesions. The mean
      diameter on CT-scan was 25.3 mm and the clinical size correlated well with the
      pathological size. Sixty percent of the tumors were ovoid and 68% had smooth
      margins. The mean SUVmax was 3.6 (range 1.4-12.9). All the lesions were
      completely resected. The regression analysis showed a direct correlation between
      the SUVmax and the tumor size (p = 0.004). No further correlations were found
      between the SUVmax and the other variables. None of the patients had recurrent
      disease or died during the follow-up. CONCLUSIONS: Our study showed that FDG
      PET/CT might be a useful tool in the evaluation of SPNs suspected to be bronchial
      carcinoids. When a solitary pulmonary nodule shows an ovoid/round shape and
      smooth margins on the CT scan and demonstrates an FDG uptake higher than that of
      the normal lung and with a SUVmax value >1-1.5, a carcinoid should be suspected.
      If benign lesions can be presumably excluded, surgical resection or at least a
      biopsy of the lesion is recommended.

PMID- 24305517
TI  - Subclinical nephrosclerosis is linked to left ventricular hypertrophy independent
      of classical atherogenic factors.
AB  - Recently, cardio-renal interactions have been considered to be important and it
      has been demonstrated that mild renal dysfunction is associated with left
      ventricular hypertrophy (LVH). However, the correlation between LVH and
      subclinical renal damage is unclear. We investigated this association by
      assessing pretransplant biopsies from living kidney donors with normal renal
      function. We retrospectively categorized 238 living kidney donors into tertiles
      according to the percentage of global glomerulosclerosis (%GGS) observed in
      pretransplant biopsies (low, 0-3.45% (n=80); moderate, 3.46-11.76% (n=78); high,
      ?11.77% (n=80)) to analyze trends in their left ventricular mass index (LVMI)
      measured by echocardiography and baseline factors. LVH was defined as LVMI >110 g
      m(-2) in female and >125 g m(-2) in male subjects. We used a logistic regression
      model to evaluate any correlations between %GGS and LVH. LVMI increased
      significantly with increasing tertiles of %GGS, as did the prevalence of left
      ventricular remodeling and LVH. According to multivariate logistic regression
      analysis, subjects with high %GGS tertiles had a sevenfold greater risk of LVH
      than did those with low tertiles, even after adjusting for age, sex, systolic
      blood pressure, history of diabetes mellitus, total serum cholesterol and
      glomerular filtration rate (GFR) measured by a radioisotopic technique. There is
      an association between GGS and LVH in subjects with normal renal function. This
      association is significant after adjustment for age, sex, blood pressure, GFR and
      other atherogenic factors.

PMID- 24305518
TI  - Blood pressure variability over 24 h: prognostic implications and treatment
      perspectives. An assessment using the smoothness index with telmisartan
      amlodipine monotherapy and combination.
AB  - In-office blood pressure (BP) measurements have recognized limitations, including
      the inability to collect BP information over a long period of time, and during an
      individual's usual daily activities. Home or ambulatory BP monitoring (ABPM) may
      therefore be used to complement conventional office measurements, thereby
      improving prognostic value. Of particular relevance is the ability of 24 h ABPM
      to quantify the degree of BP variability over 24 h, which has been shown to be a
      significant and independent risk factor for cardiovascular (CV) morbidity and
      mortality. Twenty-four hour BP variability is indeed strongly associated with
      clinical outcomes, and the ability of ABPM to provide a quantification of BP
      throughout the 24-h period during an individual's normal daily routine is one of
      the reasons for its high prognostic value. The smoothness index (SI) provides a
      useful measure of antihypertensive treatment efficacy over the 24 h dosing
      period, its values being highest with antihypertensive agents that have large and
      consistent effects across 24 h. Telmisartan and amlodipine are long-acting
      antihypertensive drugs that, in combination, not only reduce 24 h mean BP more
      than the respective monotherapies but also provide a significantly greater SI.
      The provision of homogeneous 24 h BP control has important clinical implications.
      Maintaining smooth BP over the entire 24 h dosing period may contribute to the
      improvement of CV outcomes, and reductions in BP variability may decrease end
      organ damage, and reduce CV risk.

PMID- 24305519
TI  - Energy metabolism in BPH/2J genetically hypertensive mice.
AB  - Recent evidence indicates that genetic hypertension in BPH/2J mice is
      sympathetically mediated, but these mice also have lower body weight (BW) and
      elevated locomotor activity compared with BPN/3J normotensive mice, suggestive of
      metabolic abnormalities. The aim of the present study was to determine whether
      hypertension in BPH/2J mice is associated with metabolic differences. Whole-body
      metabolic and cardiovascular parameters were measured over 24 h by indirect
      calorimetry and radiotelemetry respectively, in conscious young (10-13 weeks) and
      older (22-23 weeks) BPH/2J, normotensive BPN/3J and C57Bl6 mice. Blood pressure
      (BP) was greater in BPH/2J compared with both normotensive strains at both ages
      (P<0.01). Metabolic rate was greater in young BPH/2J compared with BPN/3J mice
      (P<0.01) but similar to C57Bl6 mice indicating that high metabolic rate is not
      necessarily related to the hypertension per say. The slope of the BP-metabolic
      rate relationship was comparable between BPH/2J and normotensive mice when
      adjusted for activity (P>0.1) suggesting differences in this relationship are not
      responsible for hypertension. EchoMRI revealed that percentage body composition
      was comparable in BPN/3J and BPH/2J mice (P>0.1) and both strains gained weight
      similarly with age (P=0.3). Taken together, the present findings indicate that
      hypertension in BPH/2J mice does not appear to be related to altered energy
      metabolism.

PMID- 24305520
TI  - Does a bite cause cancer? Misperceptions of breast cancer etiology among low
      income urban women in Miami, Florida.
AB  - OBJECTIVES: To explore breast cancer beliefs among a cohort of low-income, urban,
      English-speaking women in Miami, Florida, who had undergone screening
      mammography. METHODS: Four focus groups of 34 women were conducted. Discussions
      were transcribed verbatim and transcripts were analyzed separately by two
      investigators using an immersion-and-crystallization approach. Common risk
      factors were identified by consensus. RESULTS: Participants were predominantly
      African American (82%) women of low income (77% with a household income
      <$20,000/year). Common risk factors included family history, environmental
      factors, trauma, and sexual activity. There also was a perception that breast
      cancer grows rapidly and causes detectable symptoms. CONCLUSIONS: Women voiced
      some accurate and numerous inaccurate beliefs regarding the causes of breast
      cancer, suggesting a lack of knowledge about the potential benefits and harms of
      screening mammography before undergoing examination. These findings highlight the
      importance of identifying women's underlying beliefs when initiating a discussion
      of breast cancer screening and prevention to ensure that messages are mutually
      understood.

PMID- 24305521
TI  - Association of cardiac disease and alcohol use with the development of severe
      ciguatera.
AB  - OBJECTIVES: Ciguatera is a foodborne illness that causes severe gastrointestinal
      and neurologic symptoms, but the risk factors for illness are not well
      established. METHODS: In St Thomas, US Virgin Islands, we performed a case
      control study for ciguatera, enrolling 47 patients primarily through the
      emergency department and 141 age- and sex-matched controls identified through an
      island-wide survey. We used conditional logistic regression to assess health
      related risk factors for ciguatera, including comorbidities and alcohol and
      tobacco use. RESULTS: Cases were more likely than controls to report alcohol
      consumption at least weekly (odds ratio 5.7, 95% confidence interval 2.7-24.8).
      Cases also more frequently had a history of heart disease (odds ratio 6.3, 95%
      confidence interval 1.2-32.7). Previous ciguatera episodes, lower levels of
      education, and frequent fish consumption also were associated with illness.
      CONCLUSIONS: This study provides preliminary evidence that preexisting health
      status influences an individual's risk of developing severe ciguatera. There may
      be a benefit to educating high-risk individuals about preventing ciguatera.

PMID- 24305522
TI  - Safety profile of high-dose statin therapy in geriatric patients with stroke.
AB  - OBJECTIVES: Use of high-dose statin therapy (HDST) in patients with stroke became
      standard clinical practice after the Stroke Prevention by Aggressive Reduction in
      Cholesterol Levels (SPARCL) study, in which the mean age of the study population
      was approximately 63 years. Little data are available on the adverse effects of
      statins when used in high doses in adults older than 65 years. The objective of
      this study was to assess the magnitude of adverse effects of HDST in geriatric
      patients. METHODS: This single-center, retrospective, case-control study was
      conducted at Upstate Medical University, Syracuse, New York. All patients older
      than 65 years admitted between 2008 and 2011 to the hospital's Upstate Stroke
      Center with acute stroke were eligible. Electronic medical records of 200
      eligible patients were reviewed to collect demographic, clinical, and laboratory
      data. Patients on HDST (cases) were compared with those on low doses (controls)
      using the chi, Fisher exact (two-sided), and Student t tests. RESULTS: One
      hundred cases (mean age 80.5 +/- 7.7 years) were compared with 100 controls (mean
      age 78.9 +/- 6.4 years). Sixty-seven percent were taking simvastatin. Ninety
      percent of the cases compared with 81% of the controls had ischemic stroke. The
      prevalence of elevated alanine aminotransferase (13%) and myositis (4%) was
      significantly higher in the cases than in the controls. Fourteen percent of the
      cases reported myalgias, 9% had nausea, and 6% had diarrhea. Seventy-three cases
      had low-density lipoprotein levels <100 mg% and 41% of the cases had mean
      glycated hemoglobin levels >= 6.5%. CONCLUSIONS: The use of HDST in older adult
      patients with acute stroke is associated with a significantly increased burden of
      liver enzyme elevation and myalgias.

PMID- 24305523
TI  - Commentary on "safety profile of high-dose statin therapy in geriatric patients
      with stroke".

PMID- 24305524
TI  - Changing age distribution of melanoma patients: a 22-year, single-site
      perspective.
AB  - OBJECTIVES: To investigate possible changes in the demographics of patients with
      melanoma during a period of 22 years in one dermatopathology practice. METHODS:
      We performed a retrospective review of 1835 cases of in situ and invasive
      melanomas histologically diagnosed between 1989 and 2010 in a private
      dermatopathology laboratory in Norfolk, Virginia. The age and sex of patients
      with in situ and invasive melanomas were recorded and compared with similar data
      for patients from whom any histopathologic specimen was received during the same
      interval. These data were then compared with those in the national Surveillance,
      Epidemiology, and End Results (SEER) registry between 1989 and 2009. RESULTS: The
      number of melanomas diagnosed in the laboratory increased during the 22 study
      years, but the proportion of submitted specimens diagnosed as melanoma remained
      somewhat stable. Patient ages ranged from the teens to the ninth decade of life.
      The proportion of melanomas in the in situ stage gradually increased. Mean
      patient age rose from 52.4 years in 1989 to 60.7 years in 2010. Men and women
      aged 60 years and older made up an increasing proportion of melanoma cases. There
      also was a relative increase in the proportion of women in the 40- to 50-year-old
      age group and a slight increase among those aged 20 to 30 years, particularly for
      invasive lesions. In general, the trends were similar for in situ and invasive
      melanomas. Our data were consistent with the SEER data in showing a trend for
      decreasing proportion of melanomas in younger individuals, with a corresponding
      increase in the middle-age and older adult populations. Some differences between
      the two datasets emerged for men aged 70 to 80, women aged 60 to 70, and all
      patients aged 70 to 80. CONCLUSIONS: An increasing proportion of melanomas were
      diagnosed in older individuals. There also was a relative increase in women aged
      40 to 50 years and a lesser increase in those aged 20 to 30 years. Our findings
      were consistent with the national trends observed in the SEER dataset.

PMID- 24305525
TI  - Commentary on "changing age distribution of patients with melanoma".

PMID- 24305526
TI  - Sexual abuse history and pelvic floor disorders in women.
AB  - OBJECTIVES: Sexual abuse rates in the general female population range between 15%
      and 25%, and sexual abuse is known to have a long-term impact on a woman's
      health. The aim of this study was to report the prevalence of sexual abuse
      history in women presenting to clinicians for pelvic floor disorders (PFD) and to
      determine whether a history of sexual abuse is associated with a specific type of
      PFD. METHODS: We conducted a retrospective chart review of new urogynecology
      patients seen at the University of New Mexico Hospital. All women underwent a
      standardized history and physical examination and completed symptom severity and
      quality-of-life measures. Univariate and multivariable analyses were conducted to
      determine which PFDs were associated with a history of sexual abuse among women
      with and without a history of sexual abuse. RESULTS: A total of 1899 new
      urogynecology patients with complete information were identified from January
      2007 and October 2011; 1260 (66%) were asked about a history of sexual abuse. The
      prevalence of sexual abuse was 213/1260 (17%). In the multivariable analysis,
      only chronic pelvic pain remained significantly associated with a history of
      sexual abuse. CONCLUSIONS: A history of sexual abuse is common among women with
      PFDs, and these women were more likely to have chronic pelvic pain.

PMID- 24305527
TI  - Surgeons' perspectives on optimal patient positioning during simultaneous cranial
      procedures and exploratory laparotomy.
AB  - OBJECTIVES: Patients presenting with traumatic intracranial and intraabdominal
      injuries often require emergent care. Triage of injuries is based on severity of
      the individual injuries, but treatment occasionally must proceed simultaneously.
      Determining an optimal patient position at the time of surgery often produces
      unnecessary delays and this delay may negatively affect patient outcome. This
      study aimed to determine an operative patient position that simultaneously
      optimizes access to neurosurgical and general surgical teams without compromising
      sterility or severely affecting surgeon and anesthesia comfort. METHODS:
      Photographs of traditional exploratory laparotomy patient positioning (position
      A), traditional supine craniotomy patient positioning (position B), and a hybrid
      patient position (position C) were presented to 29 general surgeons and 12
      neurosurgeons at a single institution. Surgeons were asked to rate the positions
      on acceptability and to rank the three positions according to preference when
      simultaneous exploratory laparotomy and craniotomy were necessary. RESULTS:
      Position C was rated as an acceptable option by 82.8% of general surgeons and
      100% of neurosurgeons. In addition, 51.9% of general surgeons and 81.8% of
      neurosurgeons preferred position C to their respective specialty's traditional
      patient positioning in situations that required simultaneous exploratory
      laparotomy and craniotomy. CONCLUSIONS: We present a novel hybrid operative
      patient position for use during simultaneous exploratory laparotomy and
      craniotomy. In doing so, we emphasize the importance of constructive dialogue
      among trauma surgeons and neurosurgeons in optimizing the care of acutely ill
      trauma patients with multisystem injuries.

PMID- 24305528
TI  - Estimating the early impact of the FDA safety communication on the use of
      surgical mesh.
AB  - OBJECTIVES: To estimate the early impact of the July 2011 Food and Drug
      Administration Safety Communication on the practice patterns of gynecologic
      surgeons using surgical mesh to manage pelvic organ prolapse (POP) and stress
      urinary incontinence (SUI). METHODS: A cross-sectional study was performed by
      administering a mesh usage questionnaire to physician attendees at the opening
      session of the American Association of Gynecologic Laparoscopists Global Congress
      of Minimally Invasive Gynecology in November 2011. RESULTS: Of the 827 physicians
      attending the opening session of the conference, 281 (34%) completed the
      questionnaire, 202 (72%) of whom reported performing surgery for POP and/or SUI.
      The respondents were attending physicians (83.4%) with at least 10 years of
      experience (65.7%), 136 (71.1%) identifying themselves as General Gynecology, 29
      (17.3%) as Urogynecology, 13 (7.1%) as Minimally Invasive Gynecologic Surgery,
      and 3 (1.8%) as Urology. When compared with generalists, specialists were more
      likely to use mesh for abdominal (86% vs 56.3%, P < 0.001) and vaginal (65.9% vs
      37.2%, P = 0.001) POP repair. Specialists reported using mesh for the anterior
      compartment (50% vs 28.3%, P = 0.01) and the posterior compartment (36.4% vs
      12.5%, P = 0.001), and total vaginal mesh kits (13.6% vs 1.7%, P = 0.005).
      Respondents reported an increase in mesh use for primary abdominal POP repair (82
      vs 92, P = 0.013) and a decrease in mesh use for recurrent vaginal POP repair (99
      vs 75, P < 0.001), with more surgeons opting against mesh for recurrent POP (49
      vs 74, P < 0.001). For patient counseling, 53.7% reported changing their methods.
      CONCLUSIONS: In a self-selected sample of pelvic surgeons, we noted that the 2011
      FDA Safety Communication had an impact, with changes in mesh usage and counseling
      patterns.

PMID- 24305529
TI  - Minimally invasive drainage of subcutaneous abscesses reduces hospital cost and
      length of stay.
AB  - OBJECTIVE: We compared outcomes among pediatric patients managed with minimally
      invasive (MI) packing techniques with those managed with traditional packing
      techniques for drainage of subcutaneous abscesses. METHODS: After institutional
      review board approval, medical records of children requiring drainage of
      subcutaneous abscesses between January 2010 and June 2011 were reviewed. Data
      were collected on patient demographics, abscess location, surgical procedure,
      microbiology cultures, and hospital length of stay (LOS). The hospital accounting
      system was queried for direct and indirect costs. We compared LOS and cost data
      among groups managed with MI versus traditional packing techniques. RESULTS:
      Incision and drainage was performed on 329 children (57.8% girls, 72% white, mean
      age of 43 months [range <1 to 218]). Of the total abscesses 198 (60.2%) were
      located in the groin/buttocks/perineum. Methicillin-resistant Staphylococcus
      aureus was identified in 74% of culture specimens. A total of 202 patients
      (61.4%) underwent packing and 127 (38.6%) underwent MI drainage. MI drainage
      ranged from 0% (0/110) in January to June 2010 to 34.6% (44/127) in the July to
      December 2010 transition period and reached 90.2% (83/92) in 2011 (P < 0.001).
      Median LOS decreased from 2 days (interquartile range 1-2) in the packing-only
      period to 1 day (interquartile range 1-2) in the predominantly MI period (P <
      0.001). Hospital costs decreased with the transition to the MI technique (P <
      0.001). MI drainage was associated with a $520 reduction in median direct costs
      and a $385 reduction in median indirect costs (P < 0.001). CONCLUSIONS: Soft
      tissue infections requiring incision and drainage are common in the pediatric
      population, with the majority caused by methicillin-resistant Staphylococcus
      aureus. Infections requiring drainage most frequently occurred in the diaper area
      of girls younger than 3 years old. Changing to an MI technique significantly
      decreased the hospital costs and LOS in our patient population.

PMID- 24305531
TI  - Commentary on "inpatient rehabilitation centers and concern for increasing volume
      of ischemic stroke patients requiring rehabilitation".

PMID- 24305530
TI  - Inpatient rehabilitation centers and concern for increasing volume of ischemic
      stroke patients requiring rehabilitation.
AB  - OBJECTIVES: To determine whether prolonged length of stay (pLOS) in ischemic
      stroke is related to delays in discharge disposition arrangement. METHODS: We
      designed a retrospective study to compare patients with acute ischemic stroke who
      experienced pLOS to those who did not experience pLOS. Patients who have had
      acute ischemic stroke between July 2008 and December 2010 were included unless
      they arrived >48 hours after time last seen normal, had an unknown last seen
      normal, or experienced an in-hospital stroke. pLOS was defined in our prospective
      stroke registry (before the generation of this research question) as
      hospitalization extended for >= 24 hours more than necessary to determine
      neurologic stability and next level of care/disposition for a given patient. We
      characterized the frequency of each cause of pLOS and further investigated the
      destinations that were more frequently associated with pLOS among patients with
      delay resulting from arranging discharge disposition. RESULTS: Of the 274
      patients included, 106 (31.9%) had pLOS. Reasons for pLOS were discharge
      disposition (48.1%), non-neurologic medical complications (36.8%), delays in
      imaging studies (20.8%), awaiting procedure (10.4%), and neurologic complications
      (9.4%). Among patients with pLOS caused by delayed disposition, more than half
      were awaiting placement in an inpatient rehabilitation facility. CONCLUSIONS: For
      the majority of our patients, pLOS was caused by acquired medical complications
      and delayed disposition, most commonly inpatient rehabilitation. Further efforts
      are needed to prevent complications and further investigation is necessary to
      identify the factors that may contribute to delayed discharge to inpatient
      rehabilitation facilities, which may include delayed planning or heightened
      scrutiny of insurance companies regarding their beneficiaries.

PMID- 24305532
TI  - Osteoporosis in postmenopausal women: considerations in prevention and treatment:
      (women's health series).
AB  - Osteoporosis, the most common human bone disease, affects 8 million American
      women and has significant morbidity and mortality. Screening is important in
      older women and younger postmenopausal women with additional risk factors for
      osteoporosis/fracture. Preventive measures include avoiding smoking, excessive
      alcohol/caffeine intake, and falls in addition to maintaining adequate
      calcium/vitamin D intake and exercise. Estrogen/hormone therapy may be considered
      in some patients. Various medications have proven efficacy in treating
      postmenopausal osteoporosis; however, potential adverse effects such as
      hypocalcemia, worsening of renal impairment, and osteonecrosis of the jaw must be
      considered. The optimal duration of therapy requires further investigation. 

PMID- 24305533
TI  - [Picture in clinical hematology no. 67].

PMID- 24305534
TI  - [Induction of megakaryocytes and platelet production from mouse and human
      fibroblasts by p45 NF-E2/Maf].

PMID- 24305535
TI  - [Animal models of MYH9 disorders].

PMID- 24305536
TI  - [Childhood acute lymphoblastic leukemia; pathophysiology and treatment strategy].

PMID- 24305537
TI  - [Hematologic improvement with deferasirox following tandem antithymocyte globulin
      treatment in a transfusion-dependent patient with severe aplastic anemia].
AB  - A 62-year-old man with transfusion-dependent severe aplastic anemia received
      immunosuppressive therapy (IST) with rabbit antithymocyte globulin and
      cyclosporine A in April 2010. However, his transfusion dependency did not
      improve. As more than 100 red blood cell (RBC) transfusions had been performed,
      he was administered iron chelation therapy (ICT) with deferasirox (DFX) to
      improve iron overload starting in July 2011. Consequently, both RBC and platelet
      transfusion dependency gradually improved concomitant with a decrease in serum
      ferritin. The bone marrow (BM) biopsy findings before administration of DFX
      showed severe iron accumulation and strong positive immunostaining for 8-OHdG, a
      marker of oxidative stress due to free iron. One year after ICT, the number of BM
      hematopoietic cells was increased and both iron deposition and oxidative stress
      were decreased. These findings suggest that DFX may contribute to hematological
      improvement in patients with IST-refractory aplastic anemia. 

PMID- 24305538
TI  - [Successful treatment with rituximab in a patient with refractory mixed-type
      autoimmune hemolytic anemia].
AB  - The evidence that rituximab is effective therapy for refractory warm or cold
      autoimmune hemolytic anemia (AIHA) has been accumulating; however, the efficacy
      of rituximab for mixed-type AIHA is not evident. Herein, we report a case of
      mixed-type AIHA refractory to corticosteroids and splenectomy, but successfully
      treated with rituximab (375 mg/m(2)/day, once weekly, four times). She achieved a
      complete response, which has been maintained for 16 months, to date, despite
      steroid tapering. Our case suggests that rituximab therapy should be considered
      for refractory AIHA even of mixed-type. 

PMID- 24305539
TI  - [Composite lymphoma cosisting of mantle cell lymphoma and follicular lymphoma].
AB  - Herein, we report the case of a 56-year-old man with composite lymphoma (CL)
      comprised of mantle cell lymphoma (MCL) and follicular lymphoma (FL). Six months
      after developing a right brachial tumor, he was diagnosed as having grade 3 FL
      with normal-size mantle zone. Simultaneously, advanced stage MCL with a diffuse
      growth pattern in a sigmoid colon tumor and abnormal lymphoid cells in bone
      marrow were observed. Thereafter, the right brachial tumor was re-examined and
      its mantle zone cells were immunophenotypically positive for cyclin D1 (CCND1)
      and cytogenetically positive for the IgH-CCND1 fusion gene. Consequently, he was
      diagnosed with composite lymphoma (CL) comprised of FL and MCL. As MCL and FL may
      form CL, the possible complication of MCL should be considered and steps taken to
      detect MCL. 

PMID- 24305540
TI  - [Composite lymphoma consisting of adult T-cell leukemia-lymphoma and diffuse
      large B-cell lymphoma].
AB  - A 68-year-old man was admitted to our hospital because of left back pain and
      systemic lymphadenopathy with hypercalcemia. Serum anti-HTLV-1 antibody was
      positive. Left cervical lymph node (LN) biopsy revealed proliferation of medium
      sized to large CD4-positive atypical cells with modest infiltration of CD20 and
      Epstein-Barr virus (EBV)-encoded RNA dual-positive atypical large cells.
      Monoclonal integration of HTLV-1 proviral DNA, plus clonal rearrangement of the T
      cell receptor chain gene and the immunoglobulin heavy chain gene, were detected
      in the same LN specimen. Composite lymphoma consisting of adult T-cell
      leukemia/lymphoma (ATL) and EBV positive diffuse large B-cell lymphoma (DLBCL)
      was diagnosed. He was successfully treated with aggressive chemotherapy including
      rituximab and attained remission. However, eight months later, he developed right
      shoulder pain due to multiple bone invasions with bilateral cervical
      lymphadenopathy. Biopsies of a bone lesion and cervical LN revealed recurrence of
      ATL alone. The patient died despite salvage chemoradiotherapy. These findings
      suggest that ATL-related immunodeficiency might induce EBV-associated DLBCL. 

PMID- 24305541
TI  - [Follicular lymphoma complicated with myelofibrosis and macroglobulinemia at
      initial presentation].
AB  - A 49-year-old woman presented with pharyngeal and cervical lymph node swelling in
      December 2010. Biopsy of the pharynx demonstrated follicular lymphoma which
      secreted large volumes of immunoglobulin M (IgM) and transforming growth factor
      beta (TGF-beta). Bone marrow aspiration yielded a dry tap, and bone marrow biopsy
      demonstrated myelofibrosis associated with lymphoma cells on admission. The
      plasma concentration of TGF-beta was elevated and monoclonal IgM gammopathy was
      detected. After only one course of chemotherapy with CHOP plus rituximab,
      remission of both lymphoma and myelofibrosis was achieved. Bone marrow aspiration
      became possible, and TGF-beta and IgM levels normalized. Thus, the myelofibrosis
      was reversible. 

PMID- 24305542
TI  - [Detection of BCR-ABL1 chimeric gene-positive neutrophils in a patient with mixed
      phenotype acute leukemia].
AB  - We experienced two patients with mixed phenotype acute leukemia with
      t(9;22)(q34;q11.2); BCR-ABL1 according to the WHO classification 2008. The type
      of BCR/ABL1 was major in both patients, and the chimeric gene was also detected
      in neutrophils from peripheral blood by the fluorescence in situ hybridization
      technique. Patient 1 was a 59-year-old Japanese woman, and patient 2 a 45-year
      old Japanese man. They had both developed leukemia suddenly. Their leukemic
      blasts expressed B cell and myeloid cell antigens, but concomitantly in patient 1
      (biphenotypic) and separately in patient 2 (biclonal). Percentages of BCR-ABL1
      positive neutrophils were 98% and 89%, respectively. Both patients received an
      imatinib (600 mg/day)-combined Hyper-CVAD regimen as induction therapy, followed
      by treatment with dasatinib (140 mg/day). MEC therapy was also applied between
      these two treatments in patient 2. At present, patient 1 has obtained complete
      molecular remission quantitatively and qualitatively, and patient 2 only
      quantitatively. Considering their acute onsets with no prior history of chronic
      myelocytic leukemia (CML), they were both diagnosed as having acute leukemia with
      Ph1, but not blastic crisis of CML. In this tyrosine kinase inhibitor era, it has
      become more difficult to differentiate these two types of Ph1-positive leukemia
      development. 

PMID- 24305543
TI  - [Recent trend in the incidence of hematologic disease in Japan: a report from
      Statistical Research Comittee of Japanese Society of Hematology].

PMID- 24305546
TI  - Increased isobutanol production in Saccharomyces cerevisiae by eliminating
      competing pathways and resolving cofactor imbalance.
AB  - BACKGROUND: Isobutanol is an important target for biorefinery research as a next
      generation biofuel and a building block for commodity chemical production.
      Metabolically engineered microbial strains to produce isobutanol have been
      successfully developed by introducing the Ehrlich pathway into bacterial hosts.
      Isobutanol-producing baker's yeast (Saccharomyces cerevisiae) strains have been
      developed following the strategy with respect to its advantageous characteristics
      for cost-effective isobutanol production. However, the isobutanol yields and
      titers attained by the developed strains need to be further improved through
      engineering of S. cerevisiae metabolism. RESULTS: Two strategies including
      eliminating competing pathways and resolving the cofactor imbalance were applied
      to improve isobutanol production in S. cerevisiae. Isobutanol production levels
      were increased in strains lacking genes encoding members of the pyruvate
      dehydrogenase complex such as LPD1, indicating that the pyruvate supply for
      isobutanol biosynthesis is competing with acetyl-CoA biosynthesis in
      mitochondria. Isobutanol production was increased by overexpression of enzymes
      responsible for transhydrogenase-like shunts such as pyruvate carboxylase, malate
      dehydrogenase, and malic enzyme. The integration of a single gene deletion
      lpd1Delta and the activation of the transhydrogenase-like shunt further increased
      isobutanol levels. In a batch fermentation test at the 50-mL scale from 100 g/L
      glucose using the two integrated strains, the isobutanol titer reached 1.62 +/-
      0.11 g/L and 1.61 +/- 0.03 g/L at 24 h after the start of fermentation, which
      corresponds to the yield at 0.016 +/- 0.001 g/g glucose consumed and 0.016 +/-
      0.0003 g/g glucose consumed, respectively. CONCLUSIONS: These results demonstrate
      that downregulation of competing pathways and metabolic functions for resolving
      the cofactor imbalance are promising strategies to construct S. cerevisiae
      strains that effectively produce isobutanol.

PMID- 24305547
TI  - Urinary Neutrophil Gelatinase-Associated Lipocalin predicts the severity of
      contrast-induced acute kidney injury in chronic kidney disease patients
      undergoing elective coronary procedures.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) particularly in high
      risk patients with chronic kidney disease (CKD), increases morbidity and
      mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein
      excreted by the kidney during AKI. There are no urine (u) NGAL data as an early
      CI-AKI marker in CKD patients undergoing coronary procedures. METHODS: This
      prospective study enrolled 130 patients with estimated glomerular filtration rate
      (eGFR) < 60 ml/min/1.73 m2 undergoing elective coronary procedures. Serial urine
      samples, obtained at baseline and 3, 6, 12, 18, and 24 h post contrast
      administration were analyzed by NGAL ELISA kit. AKI was defined as an increase in
      serum creatinine (SCr) of >= 0.3 mg/dl or >= 1.5 times baseline SCr within 48 h
      per 2012 KDIGO guidelines. Receiver operator characteristic curve analyses
      identified optimal uNGAL and delta of uNGAL values for diagnosing CI-AKI.
      RESULTS: The uNGAL was significantly and inverse correlated with eGFR (R = 0.25,
      P < 0.005). CI-AKI developed in 16/130 (12.31%) patients: 13 and 3 in CI-AKI
      stages I and II, respectively. uNGAL and delta of uNGAL were significantly higher
      in the CI-AKI group when compared with the No CI-AKI group (P < 0.05). The best
      uNGAL cut-off for optimal sensitivity 94%, specificity 78%, and area under the
      curve 0.84 for predicting CI-AKI was 117 ng/mL at 6 h, respectively.
      Corresponding values for predicting CI-AKI stage II were 100%, 87% and 0.9 when
      using an uNGAL of 264 ng/mL at 6 h. CONCLUSIONS: Monitoring of uNGAL levels not
      only provide the early detecting CI-AKI but also predict the severity of CI-AKI
      in CKD patients undergoing elective coronary procedures.

PMID- 24305548
TI  - Guiding the osteogenic fate of mouse and human mesenchymal stem cells through
      feedback system control.
AB  - Stem cell-based disease modeling presents unique opportunities for mechanistic
      elucidation and therapeutic targeting. The stable induction of fate-specific
      differentiation is an essential prerequisite for stem cell-based strategy. Bone
      morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad
      phosphorylation, leading to the osteogenic differentiation of mesenchymal
      stromal/stem cells (MSC) in vitro; however, it requires supra-physiological
      concentrations, presenting a bottleneck problem for large-scale drug screening.
      Here, we report the use of a double-objective feedback system control (FSC) with
      a differential evolution (DE) algorithm to identify osteogenic cocktails of
      extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in
      combination with physiologically relevant doses of dexamethasone, ascorbic acid,
      beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated
      in vitro mineralization of mouse and human MSC. These results provide insight
      into constructive approaches of FSC to determine the applicable functional and
      physiological environment for MSC in disease modeling, drug screening and tissue
      engineering. 

PMID- 24305549
TI  - Reduction in oral corticosteroid use in patients receiving omalizumab for
      allergic asthma in the real-world setting.
AB  - BACKGROUND: Oral corticosteroids (OCS) are commonly administered in patients with
      severe persistent allergic asthma. Despite their efficacy, they are associated
      with a wide variety of adverse events. The eXpeRience registry was set up to
      investigate real-world outcomes among patients receiving omalizumab for the
      treatment of uncontrolled allergic asthma. Here, we present the effect of
      omalizumab treatment on OCS use. METHODS: eXpeRience was a 2-year, multinational,
      non-interventional, observational registry of patients receiving omalizumab for
      uncontrolled allergic asthma. OCS use (proportion of patients on maintenance OCS,
      mean total daily OCS dose and change in status of OCS therapy) was assessed at
      baseline, 16 weeks, and 8, 12, 18, and 24 months after the initiation of
      omalizumab. Response to omalizumab was assessed using the physician's Global
      Evaluation of Treatment Effectiveness (GETE) at approximately Week 16. Safety
      data were also recorded. RESULTS: A total of 943 patients (mean age, 45 years;
      female, 64.9%) were enrolled in the registry, 263 of whom were receiving
      maintenance OCS at baseline. The proportion of patients taking maintenance OCS
      was markedly lower at Months 12 (16.1%) and 24 (14.2%) than at baseline (28.6%;
      intent-to-treat population). GETE status was determined in 915 patients receiving
      omalizumab: 64.2% were responders (excellent or good response), 30.7% were non
      responders (moderate, poor or worsening response); 5.1% had no assessment. The
      frequency of serious adverse events was comparable to that seen in controlled
      trials of omalizumab. CONCLUSIONS: Omalizumab use is associated with an OCS
      sparing effect in patients with uncontrolled persistent allergic asthma in the
      real-world setting.

PMID- 24305550
TI  - Quantitative metabolic imaging using endogenous fluorescence to detect stem cell
      differentiation.
AB  - The non-invasive high-resolution spatial mapping of cell metabolism within
      tissues could provide substantial advancements in assessing the efficacy of stem
      cell therapy and understanding tissue development. Here, using two-photon excited
      fluorescence microscopy, we elucidate the relationships among endogenous cell
      fluorescence, cell redox state, and the differentiation of human mesenchymal stem
      cells into adipogenic and osteoblastic lineages. Using liquid chromatography/mass
      spectrometry and quantitative PCR, we evaluate the sensitivity of an optical
      redox ratio of FAD/(NADH + FAD) to metabolic changes associated with stem cell
      differentiation. Furthermore, we probe the underlying physiological mechanisms,
      which relate a decrease in the redox ratio to the onset of differentiation.
      Because traditional assessments of stem cells and engineered tissues are
      destructive, time consuming, and logistically intensive, the development and
      validation of a non-invasive, label-free approach to defining the spatiotemporal
      patterns of cell differentiation can offer a powerful tool for rapid, high
      content characterization of cell and tissue cultures. 

PMID- 24305551
TI  - Haploid genomes illustrate epigenetic constraints and gene dosage effects in
      mammals.
AB  - Sequencing projects have revealed the information of many animal genomes and
      thereby enabled the exploration of genome evolution. Insights into how genomes
      have been repeatedly modified provide a basis for understanding evolutionary
      innovation and the ever increasing complexity of animal developmental programs.
      Animal genomes are diploid in most cases, suggesting that redundant information
      in two copies of the genome increases evolutionary fitness. Genomes are well
      adapted to a diploid state. Changes of ploidy can be accommodated early in
      development but they rarely permit successful development into adulthood. In
      mammals, epigenetic mechanisms including imprinting and X inactivation restrict
      haploid development. These restrictions are relaxed in an early phase of
      development suggesting that dosage regulation appears less critical. Here we
      review the recent literature on haploid genomes and dosage effects and try to
      embed recent findings in an evolutionary perspective. 

PMID- 24305552
TI  - Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by
      driving epithelial-mesenchymal transition.
AB  - The high incidence of recurrence and the poor prognosis of hepatocellular
      carcinoma (HCC) necessitate the discovery of new predictive markers of HCC
      invasion and prognosis. In this study, we evaluated the expression pattern of two
      members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40
      normal hepatic tissue specimens, 149 HCC specimens and their adjacent non
      tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated
      in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6%
      (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely
      detected in adjacent non-tumourous tissues and were never detected in normal
      hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated
      with poor prognosis. In addition, MSI2 up-regulation correlated with
      clinicopathological parameters representative of highly invasive HCC. Further
      study indicated that MSI2 might enhance invasion of HCC by inducing epithelial
      mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the
      invasion of HCC cells and changed the expression pattern of EMT markers.
      Moreover, immunohistochemistry assays of 149 HCC tissue specimens further
      confirmed this correlation. Taken together, the results of our study demonstrated
      that MSI2 correlates with EMT and has the potential to be a new predictive
      biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of
      post-operative HCC patients.

PMID- 24305553
TI  - Balony: a software package for analysis of data generated by synthetic genetic
      array experiments.
AB  - BACKGROUND: Synthetic Genetic Array (SGA) analysis is a procedure which has been
      developed to allow the systematic examination of large numbers of double mutants
      in the yeast Saccharomyces cerevisiae. The aim of these experiments is to
      identify genetic interactions between pairs of genes. These experiments generate
      a number of images of ordered arrays of yeast colonies which must be analyzed in
      order to quantify the extent of the genetic interactions. We have designed
      software that is able to analyze virtually any image of regularly arrayed
      colonies and allows the user significant flexibility over the analysis procedure.
      RESULTS: "Balony" is freely available software which enables the extraction of
      quantitative data from array-based genetic screens. The program follows a multi
      step process, beginning with the optional preparation of plate images from single
      or composite images. Next, the colonies are identified on a plate and the pixel
      area of each is measured. This is followed by a scoring module which normalizes
      data and pairs control and experimental data files. The final step is analysis of
      the scored data, where the strength and reproducibility of genetic interactions
      can be visualized and cross-referenced with information on each gene to provide
      biological insights into the results of the screen. CONCLUSIONS: Analysis of SGA
      screens with Balony can be either automated or highly interactive, enabling the
      user to customize the process to their specific needs. Quantitative data can be
      extracted at each stage for external analysis if required. Beyond SGA, this
      software can be used for analyzing many types of plate-based high-throughput
      screens.

PMID- 24305554
TI  - Focused plasmonic trapping of metallic particles.
AB  - Scattering forces in focused light beams push away metallic particles. Thus,
      trapping metallic particles with conventional optical tweezers, especially those
      of Mie particle size, is difficult. Here we investigate a mechanism by which
      metallic particles are attracted and trapped by plasmonic tweezers when surface
      plasmons are excited and focused by a radially polarized beam in a high-numerical
      aperture microscopic configuration. This contrasts the repulsion exerted in
      optical tweezers with the same configuration. We believe that different types of
      forces exerted on particles are responsible for this contrary trapping behaviour.
      Further, trapping with plasmonic tweezers is found not to be due to a gradient
      force balancing an opposing scattering force but results from the sum of both
      gradient and scattering forces acting in the same direction established by the
      strong coupling between the metallic particle and the highly focused plasmonic
      field. Theoretical analysis and simulations yield good agreement with
      experimental results. 

PMID- 24305555
TI  - Adsorption of NGF and BDNF derived peptides on gold surfaces.
AB  - This study tackles the interaction between gold surfaces and two peptide
      fragments named NGF(1-14) and BDNF(1-12), able to mimic the proliferative
      activity of the nerve growth factor (NGF) and the brain derived neurotrophic
      factor (BDNF), respectively. The physical adsorption processes on the solid
      surface from both single and binary peptide solutions, at physiological and acid
      pH, were investigated by QCM-D and CD experiments, as well as by molecular
      dynamics calculations. The relevant physicochemical properties at the hybrid bio
      interface, including peptide-surface interaction, conformational changes,
      hydrodynamic thickness, viscoelastic parameters, and competitive vs. synergic
      behaviour of the two peptide fragments towards the surface, were scrutinized.
      Biological assays with neuronal cells pointed to the maintenance of the
      biological activity of NGF(1-14) and BDNF(1-12) peptide molecules within the
      adlayers on the gold surface. 

PMID- 24305556
TI  - The association between indoor temperature and body mass index in children: the
      PIAMA birth cohort study.
AB  - BACKGROUND: Several experimental studies showed consistent evidence for decreased
      energy expenditure at higher ambient temperatures. Based on this, an association
      between thermal exposure and body weight may be expected. However, the effect of
      thermal exposure on body weight has hardly been studied. Therefore, this study
      investigated the association between indoor temperature and body mass index (BMI)
      in children in real life. METHODS: This longitudinal observational study included
      3 963 children from the Dutch Prevention and Incidence of Asthma and Mite Allergy
      (PIAMA) birth cohort that started in 1996. These children were followed from
      birth until the age of 11 years. Winter indoor temperature (living room and
      bedroom) was reported at baseline and BMI z-scores were available at 10
      consecutive ages. Missing data were multiply imputed. Associations between indoor
      temperature and BMI were analyzed using generalized estimating equations (GEE),
      adjusted for confounders and stratified by gender. In a subgroup of 104 children,
      bedroom temperature was also measured with data loggers. RESULTS: Mean reported
      living room and bedroom temperature were 20.3 degrees C and 17.4 degrees C,
      respectively. Reported and measured bedroom temperatures were positively
      correlated (r = 0.42, p = 0.001).Neither reported living room temperature (-0.03
      <= beta >= 0.04) and bedroom temperature (-0.01 <= beta >= 0.02) nor measured
      bedroom temperature (-0.04 <= beta >= 0.05) were associated with BMI z-score
      between the age of 3 months and 11 years. CONCLUSIONS: This study in children did
      not support the hypothesized association between indoor temperature and BMI in a
      real life setting.

PMID- 24305558
TI  - Perception of pharmacovigilance among doctors in a tertiary care hospital:
      influence of an interventional lecture.
AB  - INTRODUCTION: One of the important pillars of an efficient pharmacovigilance
      system is contribution by healthcare professionals in the form of spontaneous
      reporting. This study was aimed at investigating the knowledge, attitude and
      practice of spontaneous ADR reporting among doctors in a teaching hospital in
      Pune, and to analyze the effect of an informative lecture about Pharmacovigilance
      on the same. METHODOLOGY: This was an interventional study conducted among 220
      doctors at a tertiary care teaching hospital, Pune. Each participant was
      explained the purpose of study and asked to fill in a questionnaire about their
      knowledge, attitude and practice of pharmacovigilance. Only 80 of them attended
      the interventional lecture on Pharmacovigilance and again filled up the
      questionnaire after a period of one month from this intervention. RESULTS: Merely
      7.5% of the participants knew ADR reporting system in India. Majority of the
      respondents (95%) knew that, as doctors, they could report ADRs but were unaware
      about the methodology to report (92.5%) which affected their practice of
      Pharmacovigilance. All (100%) the participants expressed that proper training
      should be provided to clinicians for ADR reporting & 81% felt ADR reporting
      should be made mandatory. Only 80 participants (36.4%) attended the
      interventional lecture which reflected a poor response. Intervention improved
      their (96%) knowledge about ADR reporting system and now majority of them (92%)
      agreed that all sort of ADRs should be reported (p < 0.001). CONCLUSION: Attitude
      towards ADR reporting was positive but knowledge about ADR reporting system was
      inadequate among doctors working in a teaching hospital in Pune. Education helped
      in improving knowledge and had an impact on attitude of participants regarding
      pharmacovigilance.

PMID- 24305557
TI  - A novel approach to rapidly prevent age-related cognitive decline.
AB  - The loss of cognitive function is a pervasive and often debilitating feature of
      the aging process for which there are no effective therapeutics. We hypothesized
      that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria,
      Australia) would enhance cognition in aged rodents. We show here that PBT2
      rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze,
      concomitant with increases in dendritic spine density, hippocampal neuron number
      and markers of neurogenesis. There were also increased levels of specific
      glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and
      N-methyl-D-aspartate), the glutamate transporter (VGLUT1) and glutamate itself.
      Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII)
      and phosphorylated CaMKII, CREB, synaptophysin] were also increased following
      PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion
      specific increase in hippocampal zinc, which is increasingly recognized as a
      potent neuromodulator. These data demonstrate that metal chaperones are a novel
      approach to the treatment of age-related cognitive decline.

PMID- 24305559
TI  - A study on pharmacovigilance of herbal medicines in Lagos West Senatorial
      District, Nigeria.
AB  - BACKGROUND: There is an increasing use of herbal products and herbal medicines
      globally with the belief that herbal medicines are always 'safe' and carry no
      risk because they are from natural sources. However, there are concerns regarding
      medicinal plants and their ability to produce adverse effects. The growing herbal
      medicine usage has increased the need to monitor the safety of herbal medicines.
      Thus, the recommended approach by the World Health Organization (WHO) is to
      include herbal medicines in existing national pharmacovigilance systems.
      OBJECTIVE: This study aimed to determine the knowledge of pharmacovigilance of
      herbal medicines amongst herbal medicine practitioners. METHODS: The study was
      carried out in Lagos West Senatorial District of Lagos State, Nigeria. Three
      categories of practitioners (378 respondents) were engaged and they include
      Traditional Herbal Sellers, Natural Health Practitioners and Pharmacists.
      RESULTS: The results showed that herbal medicines are commonly recommended for
      malaria, typhoid, diabetes and fever. 281 (74.3%) of the respondents claimed that
      herbal medicines have no adverse effects and only 91 (24.1%) of the respondents
      said there were some adverse effects reported by the users. Adverse effects
      reported include nausea, diarrhoea and weight loss. Amongst those that received
      reports of adverse effects, only 19 (20.9%) documented these reported adverse
      effects; none of these documentations were forwarded to the regulatory bodies or
      national pharmacovigilance centre in Nigeria. CONCLUSIONS: These results showed
      inadequate adverse effects monitoring (Pharmacovigilance) amongst the
      practitioners and underscore the necessity to educate and enlighten herbal
      medicine practitioners on the need for pharmacovigilance activity of herbal
      products.

PMID- 24305560
TI  - Impact of training on Nigerian healthcare professionals' knowledge and practice
      of pharmacovigilance.
AB  - BACKGROUND: Pharmacovigilance is the science and activities relating to the
      detection, assessment, understanding and prevention of adverse effects or any
      other possible drug related problem.. The effectiveness of this system revolves
      on the active participation of the healthcare practitioners. Poor knowledge and
      practice of pharmacovigilance has necessitated training of healthcare
      professionals in different parts of Nigeria. OBJECTIVES: The objectives of this
      study are to determine the knowledge and practice of pharmacovigilance amongst
      health professionals in Nigeria and the impact of previous training in
      pharmacovigilance on their knowledge and practice. METHODS: In this descriptive
      cross sectional study, purposive and systematic random sampling method was used
      in selecting health facilities and health care practitioners respectively. Data
      were collected using a three-part peer-reviewed structured questionnaire
      administered through electronic mail (25) and self administration by healthcare
      professionals (316). RESULTS: Respondents who had received training on
      pharmacovigilance had better knowledge of correct definition of pharmacovigilance
      (P = 0.001) and better theoretical knowledge and practice scores of
      pharmacovigilance (P = 0.001). Receiving quarterly newsletters was not
      significantly associated (p = 0.220) with improved knowledge of
      pharmacovigilance. Overall, knowledge and practice of pharmacovigilance in
      Nigeria was still below average. The main challenges faced in the reporting and
      detecting of ADR were lack of awareness, poor communication, lack of continuity
      in training and poor funding. CONCLUSION: Although training was associated with
      improved knowledge and practice of pharmacovigilance amongst the health care
      providers studied, its overall impact was mild. Strengthened awareness creation
      and innovations in PV training methods are necessary to improve the efficiency of
      the program.

PMID- 24305561
TI  - Narcotic administration and fall-related injury in the hospital: implications for
      patient safety programs and providers.
AB  - OBJECTIVE: Identify factors that predict fall-related injury in hospitalized
      adults. DESIGN: Retrospective records review. SETTING: 435-bed university
      hospital. PARTICIPANTS: Inpatients with reported falls in 2010. RESULTS: Medical
      records were available for 286/293 (98%) of reported falls in 251 patients. 25%
      (63/286) of falls were associated with injury, 4% (11/286) with serious injury.
      Compared to all fallers, patients with injury did not differ by gender or age. In
      univariate analysis, patients who reported hitting their head, had pre-fall
      confusion, or who received narcotics within 24 hours before falling were more
      likely to suffer injury (estimated odds ratios 6.04, 2.00 and 5.1, respectfully).
      In multivariate analysis, receiving a narcotic prior to falling was the strongest
      predictor of injury (estimated odds ratio 5.38; 95% confidence intervals 2.07
      13.98, p < 0.001). CONCLUSIONS: In this single-institution study, 25% of patients
      who fell suffered injury and 4% serious injury. Neither age nor gender predicted
      fall-related injury. Recent narcotic administration was the strongest predictor
      of injury. Strategies to prevent fall-related injury in the hospital should
      target patients receiving narcotics. When evaluating inpatients who have fallen,
      providers should be especially vigilant about injury in patients who have pre
      fall confusion, hit their head, or have received recent narcotics.

PMID- 24305562
TI  - Comparative regulatory performance on introduction & withdrawal of drugs in India
      and EU/internationally.
AB  - BACKGROUND: With globalization and signing of WTO GATT treaty, the market in
      India has expanded. This has necessitated important regulatory decisions.
      OBJECTIVE: This study aims to determine the gap in introduction and withdrawal of
      drugs in India and EU. METHODS: For drugs prohibited for manufacture and
      sale(withdrawn) in India during 1983-1998 and 1999-2012 periods, data on year of
      introduction and withdrawal in India and EU/internationally was extracted from
      Central Drugs Standard Control Organization (CDSCO), European Medical Agency
      (EMA) websites and Google search engine and compared. RESULTS: The gap in
      introduction of drug in India compared to EU/internationally during 1999-2012
      period is shorter than 1983-1998 period, while the gap in withdrawal has not
      changed much. CONCLUSION: Regulatory authority in India has approved drugs in
      recent year more quickly than the past but gap in withdrawal has not shortened,
      indicating need for strengthening postmarketing studies and review process.

PMID- 24305563
TI  - Nimesulide controversy: a comparison of EU and Indian scenario.
AB  - BACKGROUND: Regulatory decision for withdrawal of a drug from market in European
      Union (EU) or other developed countries poses a challenge to authorities in
      developing countries specially when decision varies from different countries,
      such as for nimesulide. OBJECTIVES: To compare and evaluate, benefit and risk
      data for regulatory action, of nimesulide in India and EU. METHODS: Data on
      Nimesulide from EU available from Report on EMA website and Indian data from
      published literature (SCOPUS data base), WHO Vigibase and International Medicines
      Statistics (IMS) was compared. RESULTS: Publications from India on Adverse drug
      reactions (ADRs) are case reports (10) and case series (14). Drug Utilization
      Research (DUR) studies (17) are mostly from tertiary centres. Data in the WHO
      Vigibase is meagre, data from IMS is not easily available and there is regional
      variation in prescriptions. Thus incidence of ADRs per sale, prescription or
      defined daily does (DDD) cannot be calculated, as has been done for EU.
      CONCLUSION: Limited and varying data in post marketing studies on ADRs and drug
      utilization for nimesulide from India made regulatory decision difficult. India
      and other similar countries could contribute to post marketing data for local and
      global regulatory decisions by systematically planned studies and networking
      within country and across countries in region.

PMID- 24305564
TI  - UMC/WHO news release 12 July 2013.

PMID- 24305565
TI  - WHO Patient Safety Programme.

PMID- 24305567
TI  - Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque
      destabilization/rupture in mice by regulating the recruitment of inflammatory
      monocytes.
AB  - BACKGROUND: Preventing atherosclerotic plaque destabilization and rupture is the
      most reasonable therapeutic strategy for acute myocardial infarction. Therefore,
      we tested the hypotheses that (1) inflammatory monocytes play a causative role in
      plaque destabilization and rupture and (2) the nanoparticle-mediated delivery of
      pitavastatin into circulating inflammatory monocytes inhibits plaque
      destabilization and rupture. METHODS AND RESULTS: We used a model of plaque
      destabilization and rupture in the brachiocephalic arteries of apolipoprotein E
      deficient (ApoE(-/-)) mice fed a high-fat diet and infused with angiotensin II.
      The adoptive transfer of CCR2(+/+)Ly-6C(high) inflammatory macrophages, but not
      CCR2(-/-) leukocytes, accelerated plaque destabilization associated with
      increased serum monocyte chemoattractant protein-1 (MCP-1), monocyte-colony
      stimulating factor, and matrix metalloproteinase-9. We prepared poly(lactic-co
      glycolic) acid nanoparticles that were incorporated by Ly-6G(-)CD11b(+) monocytes
      and delivered into atherosclerotic plaques after intravenous administration.
      Intravenous treatment with pitavastatin-incorporated nanoparticles, but not with
      control nanoparticles or pitavastatin alone, inhibited plaque destabilization and
      rupture associated with decreased monocyte infiltration and gelatinase activity
      in the plaque. Pitavastatin-incorporated nanoparticles inhibited MCP-1-induced
      monocyte chemotaxis and the secretion of MCP-1 and matrix metalloproteinase-9
      from cultured macrophages. Furthermore, the nanoparticle-mediated anti-MCP-1 gene
      therapy reduced the incidence of plaque destabilization and rupture. CONCLUSIONS:
      The recruitment of inflammatory monocytes is critical in the pathogenesis of
      plaque destabilization and rupture, and nanoparticle-mediated pitavastatin
      delivery is a promising therapeutic strategy to inhibit plaque destabilization
      and rupture by regulating MCP-1/CCR2-dependent monocyte recruitment in this
      model.

PMID- 24305568
TI  - Prediction of solute diffusivity in Al assisted by first-principles molecular
      dynamics.
AB  - Ab initio calculations of the solid-state diffusivity of solute atoms in bulk
      aluminium have previously been based on transition state theory (TST), employing
      transition state searches and systematic assessments of single jumps together
      with appropriate models of jump frequencies and correlation factors like the five
      frequency model. This work compared TST benchmark predictions of diffusivities
      with first-principles molecular dynamics (FPMD). The TST calculations were
      performed at unprecedented high precision, including the temperature dependent
      entropy of vacancy formation which has not been included in previous studies of
      diffusion in Al; this led to improved agreement with experimental data. It was
      furthermore demonstrated that FPMD can yield sufficient statistics to predict the
      frequency of single jumps, and FPMD was used to successfully predict the
      macroscopic diffusivity of Si in Al. The latter is not possible in systems with
      higher activation energies, but it was demonstrated that FPMD in such cases can
      identify which jumps are prevalent for a given defect configuration. Thus,
      information from FPMD can be used to simplify the calculation of correlation
      terms, prefactors and effective transition barriers with TST significantly. This
      can be particularly important for the study of more complicated defect
      configurations, where the number of distinct jumps rapidly increases to be
      intractable by systematic methods. 

PMID- 24305569
TI  - Prevalence and clinical implications of chromothripsis in cancer genomes.
AB  - PURPOSE OF REVIEW: A variety of mutational mechanisms shape the landscape of
      somatic mutations in cancer genomes. Although the contribution of single
      nucleotide mutations is well studied, getting a hold of structural genomic
      rearrangements is more difficult due to their complexity and diversity in sizes
      and classes. Here, we discuss the incidence of complex genomic rearrangements and
      their impact on cancer development and progression. RECENT FINDINGS: Catastrophic
      genome rearrangements have recently been described in various cancer genomes.
      Such complex genomic rearrangements may be a result of local shattering of
      chromosomes followed by reassembly of DNA fragments, a process termed
      chromothripsis. In addition, DNA replication errors may lead to complex genomic
      rearrangements in cancer. Complex reshuffling of chromosomes can cause formation
      of gene fusions, disruption of tumor suppressors, and amplification of oncogenes.
      Furthermore, the occurrence of chromothripsis has been associated with poor
      prognosis in neuroblastoma, melanoma, and multiple myeloma. SUMMARY: Complex
      genomic rearrangements, such as chromothripsis, may affect cancer gene function
      and thereby have a major impact on cancer progression, prognosis, and therapy
      response.

PMID- 24305571
TI  - How can we design low back pain intervention studies to better explain the
      effects of treatment?

PMID- 24305570
TI  - Metabolic control of tumour progression and antitumour immunity.
AB  - PURPOSE OF REVIEW: Loss of cell growth control is not sufficient to explain why
      tumours form as the immune system recognizes many malignant cells and keeps them
      in check. The local inflammatory microenvironment is a pivotal factor in tumour
      formation, as tumour-associated inflammation actively suppresses antitumour
      immunity. The purpose of this review is to evaluate emerging evidence that amino
      acid catabolism is a key feature of tumour-associated inflammation that supports
      tumour progression and immune resistance to therapy. RECENT FINDINGS: Enhanced
      amino acid catabolism in inflammatory tumour microenvironments correlates with
      carcinogen resistance and immune regulation mediated by tumour-associated immune
      cells that protect tumours from natural and vaccine-induced immunity. Interfering
      with metabolic pathways exploited by tumours is a promising antitumour strategy,
      especially when combined with other therapies. Moreover, molecular sensors that
      evolved to detect pathogens may enhance evasion of immune surveillance to permit
      tumour progression. SUMMARY: Innate immune sensing that induces amino acid
      catabolism in tumour microenvironments may be pivotal in initiating and
      sustaining local inflammation that promotes immune resistance and attenuates
      antitumour immunity. Targeting molecular sensors that mediate these metabolic
      changes may be an effective strategy to enhance antitumour immunity that prevents
      tumour progression, as well as improving the efficacy of cancer therapy.

PMID- 24305573
TI  - Editor's reply to Harlow and colleagues.

PMID- 24305572
TI  - Correlated outcomes of a pilot intervention for people injecting drugs and their
      family members in Vietnam.
AB  - BACKGROUND: The interrelationship between the well-being of injecting drug users
      (IDUs) and their family environment has been widely documented. However, few
      intervention programs have addressed the needs of both IDUs and their family
      members. METHODS: This study describes a randomized intervention pilot targeting
      83 IDUs and 83 of their family members from four communes in Phu Tho province,
      Vietnam. The IDUs and family members in the intervention condition received
      multiple group sessions, with the intent to improve psychological well-being and
      family relationships. The intervention outcomes (depressive symptoms and family
      relations) were evaluated at baseline, 3-month and 6-month follow-up assessments.
      RESULTS: Depressive symptoms and family relations reported by IDUs were found to
      be correlated to those reported by their family members. Overall, significant
      intervention effects on depressive symptoms and family relations were observed
      for both IDUs and family members. A similar improvement pattern in family
      relations emerged for both the IDU and family member samples, although the
      intervention effect of reducing depressive symptoms was more sustainable for
      family members at the 6-month assessment when compared to the IDU sample.
      CONCLUSION: The intervention pilot addressed challenges faced by IDUs and their
      family members and revealed correlated outcomes for the two groups. Findings
      suggest a vital need to include family members in future drug prevention and harm
      reduction intervention efforts.

PMID- 24305574
TI  - Epidemiologic implications of asymptomatic reinfection: a mathematical modeling
      study of norovirus.
AB  - The pathogenicity of norovirus is definitively established. However, norovirus is
      frequently detected in the stool of healthy individuals. To gain understanding of
      the apparent high prevalence of asymptomatic infection, we analyzed a dynamic
      transmission model of norovirus infection, disease, and immunity. We simulated
      norovirus epidemiology in low- and high-transmission settings by varying the
      basic reproduction number (R0). We predicted annual disease incidence values in
      children aged 0-4 years of 25% with a low R0 and 29% with a high R0. However, the
      point prevalence of asymptomatic infection rose sharply from 3% to 48% from the
      low to high R0 settings. Among older children and adults, the models projected
      that incidence of disease would rise from 6% to 16% from the low to high R0
      settings, whereas asymptomatic infection prevalence was lower in this age group.
      Asymptomatic prevalence of norovirus can change dramatically with small changes
      in R0. The ratio of prevalence in cases to controls could be high in a developed
      country and close to or even less than 1 in a high-exposure setting, despite
      similar disease incidence. These findings highlight an important limitation of
      case-control studies for pathogens for which there is suboptimal diagnostic
      specificity. 

PMID- 24305575
TI  - The combined relationship of occupational and leisure-time physical activity with
      all-cause mortality among men, accounting for physical fitness.
AB  - The aim of this study was to assess the combined relationship of occupational
      physical activity and leisure-time physical activity with all-cause mortality
      among men, while accounting for physical fitness. The prospective Belgian
      Physical Fitness Study included 1,456 male workers aged 40-55 years who were free
      of coronary heart disease at baseline. Baseline data were collected through
      questionnaires and clinical examinations from 1976 to 1978. To estimate physical
      fitness, a submaximal graded exercise test was performed on a bicycle ergometer.
      Total mortality was registered during a mean follow-up period of 16.9 years. Main
      results were obtained through Cox proportional hazards regression analysis. A
      total of 145 deaths were registered during follow-up. After adjustment for
      confounders, a significantly increased mortality rate was observed in workers who
      had low levels of both physical activity types (hazard ratio = 2.07, 95%
      confidence interval: 1.03, 4.19) but also in workers combining high occupational
      physical activity and low leisure-time physical activity (hazard ratio = 2.04,
      95% confidence interval: 1.07, 3.91); the latter finding was particularly
      pronounced among workers with a low physical fitness level. The present results
      confirm the existence of a complex interplay among different physical activity
      settings and fitness levels in predicting mortality. 

PMID- 24305576
TI  - The right ventricle revisited.

PMID- 24305577
TI  - Effect of statin pretreatment on the outcome of ST-segment elevation myocardial
      infarction in patients without prior history of coronary artery disease.
AB  - INTRODUCTION: Early statin treatment has beneficial effects on the prognosis
      after acute coronary syndromes. We investigated the impact of prior statin
      treatment on the outcome of patients without a prior history of coronary artery
      disease (CAD) who presented with ST-elevation myocardial infarction (STEMI) and
      were treated with thrombolysis. METHODS: The study enrolled 1032 consecutive
      patients who satisfied the above criteria. They were categorized into two groups,
      based on their prior statin treatment for at least 3 months before admission: the
      statin pretreatment group (n=124) and the statin-naive group (n=908). All
      patients received high-dose statins during hospitalization and were prescribed
      statins after discharge. The primary outcome was the incidence of successful
      thrombolysis, as expressed by the percentage of patients with 50% ST-segment
      resolution and complete retrosternal pain resolution at 90 minutes. Secondary
      outcomes included reduction in high-sensitivity C-reactive protein (hs-CRP) and
      CK-MB levels, and in-hospital, short- and long-term cardiovascular mortality.
      RESULTS: ST-segment resolution 50% was observed in 63.7% of the statin
      pretreatment group and in 49.1% of statin-naive patients (p<0.01). Statin
      pretreatment was associated with lower hs-CRP and peak CK-MB levels (p<0.001).
      The statin-pretreatment group had lower 30-day mortality (5.6% vs. 12.3%,
      p<0.05), whereas no significant differences were detected in in-hospital or 3
      year mortality. CONCLUSIONS: Prior statin treatment in patients without a history
      of CAD who present with STEMI is associated with successful thrombolysis,
      decreased systemic inflammation, a lesser degree of myocardial damage, and a
      possible reduction in short-term mortality.

PMID- 24305578
TI  - The usefulness of T-wave peak to T-wave end interval in identifying malignant
      arrhythmias in patients with Chagas disease.
AB  - INTRODUCTION: Abnormal ventricular repolarization has been proposed as a marker
      of arrhythmogenesis, and cardiovascular morbidity and mortality. However, little
      is known about the influence of the interval between the peak and the end of the
      T wave (Tp-Te) on the inducibility of sustained ventricular arrhythmias (VA) in
      patients with Chagas disease (CD). METHODS: Using a case-control design,
      chagasics undergoing electrophysiological study (EPS) in the last three years
      were matched by age and sex. Cases represented those with positive EPS and
      controls those with no inducible VA. Tp-Te>100 ms was considered abnormal.
      Logistic regression analysis was performed to assess the association between Tp
      Te and a positive EPS, after adjusting for confounders. RESULTS: A total of 105
      patients (mean age 56 years, 52.4% male) were included: 41 (39%) had a positive
      EPS; 85.4% with inducible VA (n=35) had non-sustained ventricular tachycardia on
      the Holter monitoring, compared to 62.5% with negative EPS (n=40, p<0.001). While
      ventricular aneurysm (adjusted OR=5.3, 95% CI: 1.11-24.96, p=0.03) and coronary
      artery disease (adjusted OR=8.8, 95% CI: 1.45-53.15, p=0.01) were associated with
      an increased risk of malignant arrhythmias, a greater ejection fraction (adjusted
      OR=0.96, 95% CI: 0.93-0.99, p<0.01) was associated with a lower risk of VA.
      Prolonged Tp-Te trended to be associated with an increased risk of induced VA
      (p=0.07). CONCLUSIONS: Ventricular aneurysm, coronary artery disease, and
      ejection fraction are associated with inducible VA. Prolonged TP-Te may have a
      modest role in the identification of patients with CD who are at high risk for
      VA. Further studies are warranted to validate our results and to correlate them
      with clinical outcomes.

PMID- 24305579
TI  - Influence of intravitreal injection of bevacizumab on systemic blood pressure
      changes in patients with exudative form of age-related macular degeneration.
AB  - INTRODUCTION: The aim of our study was to examine blood pressure (BP) changes in
      hypertensive and nonhypertensive patients after intravitreal bevacizumab
      injections and to assess whether intravitreal bevacizumab carries an associated
      vascular risk in patients with exudative ocular disease. We also aimed to
      estimate the influence of gender. METHODS: The study included 57 patients with
      age-related macular degeneration who received an intravitreal injection of 1.25
      mg (0.1 mL) of bevacizumab. We analyzed systolic and diastolic BP values
      separately. Patients were divided into males and females, and into hypertensives
      and normotensives based on their BP values. BP was measured before bevacizumab
      administration, and 10 minutes, 1 hour, 2 days, 7 days and 6 weeks after the
      injection. RESULTS: Males had a statistically significant decline in systolic BP
      values 1 hour and 6 weeks after drug administration (p<0.05). The most notable
      significant decline in diastolic BP values was for males and for normotensive
      participants 1 hour after drug administration (p<0.05), while the most notable
      decline in diastolic BP values for females and for hypertensive participants was
      7 days after drug administration, with statistical significance only for
      hypertensive patients (p<0.01). For males it was noticed that a statistically
      significant decline in diastolic BP persisted after 6 weeks (p<0.05).
      CONCLUSIONS: An intravitreal bevacizumab injection is safe as regards BP changes
      over 6 weeks post administration. Regular follow up for 6 weeks should be
      mandatory in order to promptly recognize individuals who have changes in BP
      values and include them in BP treatment in order to prevent complications.

PMID- 24305581
TI  - 3D vena contracta area to quantify severity of mitral regurgitation: a practical
      new tool?

PMID- 24305580
TI  - High-risk profile in a region with extremely elevated cardiovascular mortality.
AB  - INTRODUCTION: Although mortality rates from cardiovascular diseases have shown a
      remarkable decline in many western countries, cardiovascular mortality in
      Lithuania has remained high. It is widely accepted that half of the decline in
      cardiovascular mortality can be attributed to favourable changes in modifiable
      risk factors. METHODS: In 2006, the Lithuanian High Cardiovascular Risk Programme
      was started. A two-level approach--primary health care institutions and
      specialised cardiovascular prevention units--was applied. The cardiovascular risk
      profile was evaluated for a group of 17,031 middle-aged subjects enrolled into
      the programme at a primary level and 2908 at a specialised level. RESULTS: Among
      the persons examined, 61.8% (10,519) were female. Arterial hypertension was
      present in 60.2% of the subjects. Dyslipidaemia was present in 88.8%. Total
      cholesterol was 6.02 +/- 1.23 mmol/L, LDL cholesterol 3.74 +/- 1.09 mmol/L, HDL
      cholesterol 1.53 +/- 0.52 mmol/L, and triglycerides 1.61 +/- 1.27 mmol/L.
      Diabetes mellitus was found in 10.3%, abdominal obesity in 45.4%, and metabolic
      syndrome in 43.8% of cases. These values were even greater in high-risk subjects.
      CONCLUSIONS: In middle-aged subjects the prevalence of dyslipidaemia, arterial
      hypertension, diabetes, and metabolic syndrome was found to be high. We can
      roughly state that almost nine out of ten middle-aged subjects in Lithuania have
      established dyslipidaemia, every second one has established arterial
      hypertension, and four out of ten are obese. Hence, these are the main risk
      factors that should be considered first of all in daily clinical practice.

PMID- 24305582
TI  - Percutaneous transcatheter therapy of non-coronary structural cardiac disease.

PMID- 24305583
TI  - Multiple aortic pseudoaneurysms due to detachment of the composite graft after
      bentall operation.

PMID- 24305584
TI  - Epistenocardiac pericarditis.

PMID- 24305585
TI  - A tachycardia with varying QRS morphology and RP intervals: differential
      diagnosis and therapy.
AB  - An interesting case of a tachycardia with varying QRS morphology and RP intervals
      is presented and the electrophysiological differential diagnosis is discussed. 

PMID- 24305586
TI  - Radiofrequency ablation of post-incisional atrial flutter and high-output heart
      failure in a patient with interrupted inferior vena cava and hereditary
      hemorrhagic telangiectasia.
AB  - A 61-year-old female with a history of secundum atrial septal defect repair and
      hereditary hemorrhagic telangiectasia presented with epistaxis. She was found to
      have atypical atrial flutter with 2:1 atrioventricular conduction. Radiofrequency
      ablation was planned, but inferior vena cava interruption precluded right atrial
      (RA) access. The RA was then accessed through both subclavian veins, and
      activation mapping revealed a dense atriotomy scar in the posterolateral inferior
      RA. Wavefront propagation proceeded caudally through an area of slow conduction
      confined by the atriotomy scar. Atypical atrial flutter terminated during a
      second radiofrequency application to an isthmus confined by 2 regions of dense
      scar. The arrhythmia did not recur, although the patient later experienced
      typical atrial flutter and atrial fibrillation. High-output heart failure due to
      systemic arteriovenous shunt was confirmed by cardiac catheterization and
      improved markedly with bevacizumab therapy. 

PMID- 24305587
TI  - Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation
      therapy and advanced lung carcinoma.
AB  - The intrathoracic impedance monitor system measures impedance between the device
      case and the right ventricular coil and reflects intrathoracic fluid status. It
      is used to detect early volume overload in patients with chronic heart failure.
      We report a case of inappropriate activation of the intrathoracic impedance
      monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis. 

PMID- 24305588
TI  - Coronary vasospasm induced by cytostatic drugs: Kounis syndrome seems to be the
      most likely culprit.

PMID- 24305589
TI  - Renal denervation: the Irish experience.

PMID- 24305591
TI  - Smoking.

PMID- 24305592
TI  - Cardiovascular medicine: at the crossroads.

PMID- 24305593
TI  - Role of the Hypoxia-inducible factor-1 alpha induced autophagy in the conversion
      of non-stem pancreatic cancer cells into CD133+ pancreatic cancer stem-like
      cells.
AB  - The initiation and progression of various solid tumors, including pancreatic
      carcinoma, are driven by a population of cells with stem cell properties, namely
      cancer stem cells (CSCs). Like their normal counterparts, CSCs are also believed
      to rely on their own microenvironment termed niches to sustain the population.
      Hypoxia-inducible factor-1alpha (HIF-1alpha) is a major actor in the cell
      survival response to hypoxia. Recently, several researchers proposed that non
      stem cancer cells can convert to stem-like cells to maintain equilibrium. The
      present study focuses on whether non-stem pancreatic cancer cells can convert to
      stem-like cells and the role of HIF-1alpha and autophagy in modulating this
      conversation. The non-stem pancreatic cancer cells and pancreatic cancer stem
      like cells were separated by magnetic sorting column. Intermittent hypoxia
      enhanced stem-like properties of non-stem pancreatic cancer cells and stimulated
      the levels of HIF-1alpha, LC3-II and Beclin. Enhanced autophagy was associated
      with the elevated level of HIF-1alpha. The conversation of non-stem pancreatic
      cancer cells into pancreatic cancer stem-like cells was induced by HIF-1alpha and
      autophagy. This novel finding may indicate the specific role of HIF-1alpha and
      autophagy in promoting the dynamic equilibrium between CSCs and non-CSCs. Also,
      it emphasizes the importance of developing therapeutic strategies targeting
      cancer stem cells as well as the microenvironmental influence on the tumor. 

PMID- 24305594
TI  - Hospital discharge bags and breastfeeding at 6 months: data from the infant
      feeding practices study II.
AB  - BACKGROUND: Distribution of industry-sponsored formula sample packs to new
      mothers undermines breastfeeding. OBJECTIVE: Using data from the Infant Feeding
      Practices Study II (IFPS II), we aimed to determine whether receipt of 4
      different types of bags was associated with exclusive breastfeeding during the
      first 6 months of life. METHODS: We extracted data from IFPS II questionnaires.
      Type of discharge bag received was categorized as "formula bag," "coupon bag,"
      "breastfeeding supplies bag," or "no bag". We examined exclusive breastfeeding
      status at 10 weeks (post hoc) and at 6 months using univariate descriptive
      analyses and multivariate logistic regression models, controlling for
      sociodemographic and attitudinal variables. RESULTS: Overall, 1868 (81.4%) of
      women received formula bags, 96 (4.2%) received coupon bags, 46 (2.0%) received
      breastfeeding supplies bags, and 284 (12.4%) received no bag. By 10 weeks,
      recipients of breastfeeding supplies bags or no bag were significantly more
      likely to be exclusively breastfeeding than formula bag recipients. In the
      adjusted model, compared to formula bag/coupon bag recipients, recipients of
      breastfeeding supplies bag/no bag were significantly more likely to breastfeed
      exclusively for 6 months (odds ratio = 1.58; 95% confidence interval, 1.06-2.36).
      CONCLUSION: The vast majority of new mothers received formula sample packs at
      discharge, and this was associated with reduced exclusive breastfeeding at 10
      weeks and 6 months. Bags containing breastfeeding supplies or no bag at all were
      positively associated with exclusive breastfeeding at 10 weeks and 6 months.

PMID- 24305595
TI  - Breastfeeding during pregnancy: position paper of the Italian Society of
      Perinatal Medicine and the Task Force on Breastfeeding, Ministry of Health,
      Italy.
AB  - As more women breastfeed for longer, it is increasingly likely that women may be
      still breastfeeding when they become pregnant again. The Italian Society of
      Perinatal Medicine (SIMP) Working Group on Breastfeeding has reviewed the
      literature to determine the medical compatibility of pregnancy and breastfeeding.
      We found no evidence indicating that healthy women are at higher risk of
      miscarriage or preterm delivery if they breastfeed while pregnant. No evidence
      indicates that the pregnancy-breastfeeding overlap might cause intrauterine
      growth restriction, particularly in women from developed countries. Little
      information is available on the composition of human milk of pregnant women, and
      we found no data on the growth of infants nursed by a pregnant woman. However,
      both the composition of postpartum breast milk and the growth of the subsequent
      newborn appear to be partly affected, at least in developing countries. SIMP
      supports breastfeeding during pregnancy in the first 2 trimesters, and we believe
      it to be sustainable in the third trimester. Based on the hypothetical risk,
      caution may be warranted for women at risk of premature delivery, although no
      evidence exists that breastfeeding could trigger labor inducing uterine
      contractions. In conclusion, currently available data do not support routine
      discouragement of breastfeeding during pregnancy. Further studies are certainly
      needed to explore the consequences of breastfeeding during pregnancy on maternal
      health, on the breastfed infant, on the embryo/fetus, and, subsequently, on the
      growth of the newborn. 

PMID- 24305597
TI  - Can breastfeeding promote child health equity? A comprehensive analysis of
      breastfeeding patterns across the developing world and what we can learn from
      them.
AB  - BACKGROUND: In 2010 more than 7.7 million children died before their fifth
      birthday. Over 98% of these deaths occurred in developing countries, and recent
      estimates have attributed hundreds of thousands of these deaths to suboptimal
      breastfeeding. METHODS: This study estimated prevalence of suboptimal
      breastfeeding for 137 developing countries from 1990 to 2010. These estimates
      were compared against WHO infant feeding recommendations and combined with effect
      sizes from existing literature to estimate associated disease burden using a
      standard comparative risk assessment approach. These prevalence estimates were
      disaggregated by wealth quintile and linked with child mortality rates to assess
      how improved rates of breastfeeding may affect child health inequalities.
      RESULTS: In 2010, the prevalence of exclusive breastfeeding ranged from 3.5% in
      Djibouti to 77.3% in Rwanda. The proportion of child Disability Adjusted Life
      Years (DALYs) attributable to suboptimal breastfeeding is 7.6% at the global
      level and as high as 20.2% in Swaziland. Suboptimal breastfeeding is a leading
      childhood risk factor in all developing countries and consistently ranks higher
      than water and sanitation. Within most countries, breastfeeding prevalence rates
      do not vary considerably across wealth quintiles. CONCLUSIONS: Breastfeeding is
      an effective child health intervention that does not require extensive health
      system infrastructure. Improvements in rates of exclusive and continued
      breastfeeding can contribute to the reduction of child mortality inequalities in
      developing countries.

PMID- 24305598
TI  - Old AIMs of the exocyst: evidence for an ancestral association of exocyst
      subunits with autophagy-associated Atg8 proteins.
AB  - In a recent addendum, Oren Tzfadia and Gad Galili (PSB 2014; 9:e26732) showed
      that several Arabidopsis exocyst subunits possess consensus Atg8-interacting
      motifs (AIMs), which may mediate their interaction with the autophagy-associated
      Atg8 protein, providing thus a mechanistic base for participation of exocyst
      (sub)complexes in autophagy. However, the bioinformatically identified AIMs are
      short peptide motifs that may occur by chance. We thus performed an exhaustive
      search in a large collection of plant exocyst-derived sequences from our previous
      bioinformatic study and found that AIMs are over-represented among exocyst
      subunits of all lineages examined, including moss and club moss, compared with a
      representative sample of the Arabidopsis proteome. This is consistent with the
      proposed exocyst AIMs being biologically meaningful and evolutionarily ancient.
      Moreover, among the numerous EXO70 paralogs, the monocot-specific EXO70F clade
      appears to be exempt from the general AIM enrichment, suggesting a modification
      of the autophagy connection in a subset of exocyst variants. 

PMID- 24305599
TI  - Brain restoration as an emerging field in neurology and neuroscience.
AB  - Restoration of brain function was long thought to be impossible. However, as the
      publications in the journal Restorative Neurology and Neuroscience (RNN) for more
      than 20 years attest, clinically useful improvement can be achieved after damage
      or diseases of the brain, the retina, and the peripheral nervous system. By
      reviewing both pre-clinical studies and clinical work, we explore what
      advancements can be made today and what to expect going forward. For example, in
      the last few years we have seen a clinical focus in the area of non-invasive
      brain stimulations and rehabilitation training trials. In basic animal research
      multi-modal approaches have been presented to restore brain function with a
      combination of different treatments. We think that this is an exciting time in
      the area of restoration of brain function with many new strategies aimed at
      helping recovering their impaired neurological functions. 

PMID- 24305596
TI  - Assessment, origin, and implementation of breath volatile cancer markers.
AB  - A new non-invasive and potentially inexpensive frontier in the diagnosis of
      cancer relies on the detection of volatile organic compounds (VOCs) in exhaled
      breath samples. Breath can be sampled and analyzed in real-time, leading to
      fascinating and cost-effective clinical diagnostic procedures. Nevertheless,
      breath analysis is a very young field of research and faces challenges, mainly
      because the biochemical mechanisms behind the cancer-related VOCs are largely
      unknown. In this review, we present a list of 115 validated cancer-related VOCs
      published in the literature during the past decade, and classify them with
      respect to their "fat-to-blood" and "blood-to-air" partition coefficients. These
      partition coefficients provide an estimation of the relative concentrations of
      VOCs in alveolar breath, in blood and in the fat compartments of the human body.
      Additionally, we try to clarify controversial issues concerning possible
      experimental malpractice in the field, and propose ways to translate the basic
      science results as well as the mechanistic understanding to tools (sensors) that
      could serve as point-of-care diagnostics of cancer. We end this review with a
      conclusion and a future perspective. 

PMID- 24305602
TI  - Activation and characterization of a cryptic polycyclic tetramate macrolactam
      biosynthetic gene cluster.
AB  - Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of
      natural products with important biological activities. However, many of these
      PTMs have not been characterized. Here we apply a plug-and-play synthetic biology
      strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from
      Streptomyces griseus and discover three new PTMs. This gene cluster is highly
      conserved in phylogenetically diverse bacterial strains and contains an unusual
      hybrid polyketide synthase-nonribosomal peptide synthetase, which resembles
      iterative polyketide synthases known in fungi. To further characterize this gene
      cluster, we use the same synthetic biology approach to create a series of gene
      deletion constructs and elucidate the biosynthetic steps for the formation of the
      polycyclic system. The strategy we employ bypasses the traditional laborious
      processes to elicit gene cluster expression and should be generally applicable to
      many other silent or cryptic gene clusters for discovery and characterization of
      new natural products. 

PMID- 24305603
TI  - Stimulated leaf dark respiration in tomato in an elevated carbon dioxide
      atmosphere.
AB  - It is widely accepted that leaf dark respiration is a determining factor for the
      growth and maintenance of plant tissues and the carbon cycle. However, the
      underlying effect and mechanism of elevated CO2 concentrations ([CO2]) on dark
      respiration remain unclear. In this study, tomato plants grown at elevated [CO2]
      showed consistently higher leaf dark respiratory rate, as compared with ambient
      control plants. The increased respiratory capacity was driven by a greater
      abundance of proteins, carbohydrates, and transcripts involved in pathways of
      glycolysis carbohydrate metabolism, the tricarboxylic acid cycle, and
      mitochondrial electron transport energy metabolism. This study provides
      substantial evidence in support of the concept that leaf dark respiration is
      increased by elevated [CO2] in tomato plants and suggests that the increased
      availability of carbohydrates and the increased energy status are involved in the
      increased rate of dark respiration in response to elevated [CO2]. 

PMID- 24305604
TI  - Suppression of autophagy enhances preferential toxicity of paclitaxel to
      folliculin-deficient renal cancer cells.
AB  - BACKGROUND: Paclitaxel, a widely used chemotherapeutic drug, can induce apoptosis
      in variety of cancer cells. A previous study has shown preferential toxicity of
      paclitaxel to FLCN-deficient kidney cancer cell line, UOK257. In this report, we
      investigate the cellular and molecular mechanism of paclitaxel-induced autophagy
      and apoptosis in renal cancer cells with and without FLCN expression. METHODS:
      Two pairs of cell lines were used: FLCN siRNA-silenced ACHN cell line (ACHN-5968)
      and scrambled ACHN cell line (ACHN-sc); FLCN-null UOK257 cell line and UOK257-2
      cell line restored with ectopic expression of FLCN. Autophagy was examined by
      western blot, GFP-LC3, transmission electron microscopy, and MDC assay. Cell
      viability and apoptosis were detected using MTT assay, DAPI stain and TUNEL
      assay. After inhibition of autophagy with 3-Methyladenine (3-MA) or Beclin 1
      siRNA, cell viability and apoptosis were measured by MTT assay and TUNEL assay.
      RESULTS: After paclitaxel treatment, a dose-dependent decrease in cell viability
      and increase in apoptosis were observed in FLCN-deficient UOK257 and ACHN-5968
      cells compared to their FLCN-expressing counterparts, suggesting that renal
      cancer cells without FLCN were more sensitive to paclitaxel. Enhanced autophagy
      was found to be associated with paclitaxel treatment in FLCN-deficient RCC cells.
      The MAPK pathway was also identified as a key pathway for the activation of
      autophagy in these kidney cancer cells. Inhibition of phosphorylated ERK with ERK
      inhibitor U0126 showed a significant decrease in autophagy. Furthermore, after
      inhibition of autophagy with 3-Methyladenine (3-MA) or Beclin 1 siRNA, apoptosis
      induced by paclitaxel was significantly increased in FLCN-deficient UOK257 and
      ACHN-5968 cells. CONCLUSIONS: Preferential toxicity of paclitaxel to FLCN
      deficient kidney cancer cells is associated with enhanced autophagy. Suppression
      of autophagy further enhances paclitaxel-induced apoptosis in FLCN-deficient
      renal cancer cells. Our results suggest that paclitaxel combined with an
      autophagy inhibitor might be a potentially more effective chemotherapeutic
      approach for FLCN-deficient renal cancer.

PMID- 24305606
TI  - Excellent microwave absorption property of Graphene-coated Fe nanocomposites.
AB  - Graphene has evoked extensive interests for its abundant physical properties and
      potential applications. It is reported that the interfacial electronic
      interaction between metal and graphene would give rise to charge transfer and
      change the electronic properties of graphene, leading to some novel electrical
      and magnetic properties in metal-graphene heterostructure. In addition, large
      specific surface area, low density and high chemical stability make graphene act
      as an ideal coating material. Taking full advantage of the aforementioned
      features of graphene, we synthesized graphene-coated Fe nanocomposites for the
      first time and investigated their microwave absorption properties. Due to the
      charge transfer at Fe-graphene interface in Fe/G, the nanocomposites show
      distinct dielectric properties, which result in excellent microwave absorption
      performance in a wide frequency range. This work provides a novel approach for
      exploring high-performance microwave absorption material as well as expands the
      application field of graphene-based materials. 

PMID- 24305605
TI  - Embryonic expression of the common progeroid lamin A splice mutation arrests
      postnatal skin development.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) are
      two laminopathies caused by mutations leading to cellular accumulation of
      prelamin A or one of its truncated forms, progerin. One proposed mechanism for
      the more severe symptoms in patients with RD compared with HGPS is that higher
      levels of farnesylated lamin A are produced in RD. Here, we show evidence in
      support of that hypothesis. Overexpression of the most common progeroid lamin A
      mutation (LMNA c.1824C>T, p.G608G) during skin development results in a severe
      phenotype, characterized by dry scaly skin. At postnatal day 5 (PD5), progeroid
      animals showed a hyperplastic epidermis, disorganized sebaceous glands and an
      acute inflammatory dermal response, also involving the hypodermal fat layer. PD5
      animals also showed an upregulation of multiple inflammatory response genes and
      an activated NF-kB target pathway. Careful analysis of the interfollicular
      epidermis showed aberrant expression of the lamin B receptor (LBR) in the
      suprabasal layer. Prolonged expression of LBR, in 14.06% of the cells, likely
      contributes to the observed arrest of skin development, clearly evident at PD4
      when the skin had developed into single-layer epithelium in the wild-type animals
      while progeroid animals still had the multilayered appearance typical for skin at
      PD3. Suprabasal cells expressing LBR showed altered DNA distribution, suggesting
      the induction of gene expression changes. Despite the formation of a functional
      epidermal barrier and proven functionality of the gap junctions, progeroid
      animals displayed a greater rate of water loss as compared with wild-type
      littermates and died within the first two postnatal weeks. 

PMID- 24305607
TI  - Structural, mechanical and electronic properties of 3d transition metal nitrides
      in cubic zincblende, rocksalt and cesium chloride structures: a first-principles
      investigation.
AB  - We report systematic results from ab initio calculations with density functional
      theory on three cubic structures, zincblende (zb), rocksalt (rs) and cesium
      chloride (cc), of the ten 3d transition metal nitrides. We computed lattice
      constants, elastic constants, their derived moduli and ratios that characterize
      mechanical properties. Experimental measurements exist in the literature of
      lattice constants for rs-ScN, rs-TiN and rs-VN and of elastic constants for rs
      TiN and rs-VN, all of which are in good agreement with our computational results.
      Similarly, computed Vickers hardness (HV) values for rs-TiN and rs-VN are
      consistent with earlier experimental results. Several trends were observed in our
      rich data set of 30 compounds. All nitrides, except for zb-CrN, rs-MnN, rs-FeN,
      cc-ScN, cc-CrN, cc-NiN and cc-ZnN, were found to be mechanically stable. A clear
      correlation in the atomic density with the bulk modulus (B) was observed with
      maximum values of B around FeN, MnN and CrN. The shear modulus, Young's modulus,
      HV and indicators of brittleness showed similar trends and all showed maxima for
      cc-VN. The calculated value of HV for cc-VN was about 30 GPa, while the next
      highest values were for rs-ScN and rs-TiN, about 24 GPa. A relation (H(V) is
      proportional to theta(D)(2)) between HV and Debye temperature (thetaD) was
      investigated and verified for each structure type. A tendency for anti
      correlation of the elastic constant C44, which strongly influences stability and
      hardness, with the number of electronic states around the Fermi energy was
      observed.

PMID- 24305609
TI  - Shortened penis post penile prosthesis implantation treated with subcutaneous
      soft silicone penile implant: case report.
AB  - Penile prosthesis surgery for erectile dysfunction has the highest satisfaction
      rates among all treatment options but is often associated with subjective and
      objective loss of penile length and girth following surgery. To present a novel
      technique using a subcutaneous soft silicone implant for reversal of penile
      shortening and narrowing after prosthesis surgery, with additional gains in
      overall penile length and girth. Nine patients were treated with the insertion of
      a subcutaneous soft silicone penile implant. All patients had previously reported
      a loss in penile length (0.5-2 cm), and seven of nine patients also reported a
      loss in penile girth (0.5-2.6 cm) after penile prosthesis surgery. During a
      follow-up period of 4-24 months, penile length and girth measurements showed a
      mean increase in length of 2.4 cm (+/-0.75 cm) and a mean increase in girth of
      3.4 cm (+/-0.94 cm). The additional insertion of a subcutaneous soft silicone
      implant in patients with decreased penile length and girth after penile
      prosthesis surgery is an effective treatment option that provides reversal of
      lost penile length and girth. 

PMID- 24305610
TI  - Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite
      successful intercourse in erectile dysfunction patients.
AB  - This study was aimed to identify characteristics of ED patients who discontinued
      PDE5i despite successful intercourse. Data were collected using a questionnaire
      from 34 urologic clinics regardless of the effect (success or failure) of PDE5i
      treatment by visiting the clinics (717), e-mail (64) or post (101) for 882 ED
      patients who had previously taken any kind of PDE5i on demand four or more times.
      Discontinuation of PDE5i was defined if the patient had never taken PDE5i for the
      previous 1 year despite successful intercourse. Of the 882 patients, 485 were
      included in the final analysis. Difference in the socio-demographic, ED- and
      partner-related data between the continuation and discontinuation group and
      factors influencing discontinuation of the PDE5i were analyzed. Among 485
      respondents (mean age, 53.6), 116 (23.9%) had discontinued PDE5i use despite
      successful intercourse. Most common reasons for the discontinuation were
      'reluctant medication-dependent intercourse' (31.0%), 'spontaneous recovery of
      erectile function without further treatment' (30.2%), and 'high cost' (26.7%). In
      multiple logistic regression analysis, independent factors influencing
      discontinuation of the drug were cause of ED (psychogenic), short duration of ED,
      low education (? middle school), and religion (Catholic). In partner-related
      compliance, only partner's religion (Catholic) was a significant factor. 

PMID- 24305611
TI  - Hemospermia: long-term outcome in 165 patients.
AB  - Long-term course of hemospermia has not been addressed in the sexual medicine
      literature. We report our 15 years' experience. From 1997 to 2012, 165 patients
      presented with hemospermia. Mean age was 38 years. Mean follow-up was 83 months.
      Laboratory evaluation and testis and transabdominal ultrasonography was done in
      all. Since 2008, all sonographies were done by the first author. One patient had
      urinary tuberculosis, one had bladder tumor and three had benign lesions at
      verumontanum. One patient had bilateral partial ejaculatory duct obstruction by
      stones. All six patients had persistent, frequently recurring or high-volume
      hemospermia. All pathologies were found in young patients. In the remaining 159
      patients (96%), empiric treatment was given with a fluoroquinolone
      (Ciprofloxacin) plus an nonsteroidal anti-inflammatory drug (Celecoxib). In our
      15 years of follow-up, no patient later developed life-threatening disease.
      Diagnostic evaluation of hemospermia is not worthwhile in the absolute majority
      of cases. Advanced age makes no difference. Only high-risk patients need to be
      evaluated. The vast majority of cases may be safely and effectively treated with
      empiric therapy. Almost all patients do well in long term. 

PMID- 24305614
TI  - Magnesium(II)-catalyzed asymmetric hetero-Diels-Alder reaction of Brassard's
      dienes with isatins.
AB  - The first catalytic asymmetric hetero-Diels-Alder reaction of Brassard's dienes
      with isatins was realized using Mg(II)/N,N'-dioxide complexes as catalysts,
      affording the corresponding chiral spirolactones bearing tetrasubstituted centers
      in up to 99% yield with up to 99% ee and >99 : 1 dr within 3 hours. In the
      mechanism, based on the operando IR experiments, a predominant Diels-Alder
      pathway was found in the reaction. A possible transition state model was also
      proposed.

PMID- 24305612
TI  - Oral Bisphenol A (BPA) given to rats at moderate doses is associated with
      erectile dysfunction, cavernosal lipofibrosis and alterations of global gene
      transcription.
AB  - Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor,
      released from plastics is associated with ED in occupationally exposed workers.
      However, in rats, despite the induction of hypogonadism, apoptosis of the penile
      corporal smooth muscle (SM), fat infiltration into the cavernosal tissue and
      changes in global gene expression with the intraperitoneal administration of high
      dose BPA, ED was not observed. We investigated whether BPA administered orally
      rather than intraperitoneally to rats for longer periods and lower doses will
      lead to ED. Main outcome measures are ED, histological, and biochemical markers
      in rat penile tissues. In all, 2.5-month-old rats were given drinking water daily
      without and with BPA at 1 and 0.1 mg kg(-1) per day. Two months later, erectile
      function was determined by cavernosometry and electrical field stimulation (EFS)
      and serum levels of testosterone (T), estradiol (E2) and BPA were measured.
      Penile tissue sections were assayed by Masson (SM/collagen), Oil Red O (fat),
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) (apoptosis),
      immunohistochemistry for Oct4 (stem cells), and alpha-SM actin/calponin (SM and
      myofibroblasts), applying quantitative image analysis. Other markers were assayed
      by western blotting. DNA microarrays/microRNA (miR) assays defined transcription
      profiles. Orally administered BPA did not affect body weight, but (1) decreased
      serum T and E2; (2) reduced the EFS response and increased the drop rate; (3)
      increased within the corporal tissue the presence of fat, myofibroblasts and
      apoptosis; (4) lowered the contents of SM and stem cells, but not nerve
      terminals; and (5) caused alterations in the transcriptional profiles for both
      mRNA and miRs within the penile shaft. Long-term exposure of rats to oral BPA
      caused a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to
      alterations within the corporal tissue that pose gene transcriptional changes
      related to inflammation, fibrosis and epithelial/mesenchymal transition (EMT).

PMID- 24305615
TI  - Comparative analysis of receptor-binding specificity and pathogenicity in natural
      reassortant and non-reassortant H3N2 swine influenza virus.
AB  - Genetic reassortment between human and avian influenza viruses can create
      pandemic viruses. Influenza surveillance of pigs in Jilin Province, in China
      during 2007-2008 revealed that there were two distinguishable genotypes: a human
      like H3N2 genotype and a double-reassortant genotype derived from the human H3N2
      and avian H5 viruses. In this study, viral infection potential, replication
      kinetics, and pathogenicity were compared. The solid-phase binding assay
      demonstrated that both viruses prominently maintained a preference for the human
      type receptor and the reassortant A/swine/Jilin/37/2008 (Sw/JL/37/08) showed
      relatively higher binding affinities than the non-reassortant
      A/swine/Jilin/19/2007 (Sw/JL/19/07). Replication kinetics showed that Sw/JL/37/08
      had higher replicability in MDCK cells than Sw/JL/19/07. The mouse experiments
      clearly revealed that Sw/JL/37/08 had higher virulence than Sw/JL/19/07 as
      measured by more significant body weight loss, higher viral lung load, delayed
      viral clearance from lungs, and more severe pulmonary lesions. Sequence analysis
      indicated that the absence of glycosylation sites at residue 126 of HA and 93 of
      NA, as well as the characteristic NS1 C-terminal PL residues of ESEV may account
      for the increased replication and pathogenicity of Sw/JL/37/08. These results may
      imply that human may have infection risk by the reassortant swine influenza virus
      and emphasize the necessity for enhanced viral surveillance strategies, which
      monitor reassortment events in nature to reduce the public health threat posed by
      influenza viruses with the potential for human-to-human transmission currently
      circulating in pig populations. 

PMID- 24305617
TI  - Protonation, coordination chemistry, cyanometallate "supercomplex" formation and
      fluorescence chemosensing properties of a bis(2,2'-bipyridino)cyclophane
      receptor.
AB  - A new polyazamacrocycle (L) containing two 2,2'-bipyridino (bpy) units, where the
      heteroaromatic nitrogen atoms point outwards from the macrocyclic cavity, was
      synthesized and characterized by elemental analysis, ESI-MS, (1)H and (13)C NMR,
      FTIR and TGA. Five protonation constants involving aliphatic nitrogens with log K
      in the range 9.39-3.07 were determined by potentiometry and NMR and a sixth
      protonation (log K = 2.2) involving a bipyridine moiety could be detected by UV
      Vis and NMR titrations. The interaction of L with the cyanometallate anions
      [Pt(CN)4](2-) and [Co(CN)6](3-) was studied by potentiometry yielding
      respectively log K values in the ranges 4.0-6.4 and 5.2-10.5, covering
      protonation degrees from 1 to 5. Studies on L with [Ru(CN)6](4-) led to early
      precipitation preventing potentiometry, but crystals of [H4L][Ru(CN)6].10H2O and
      also of [H2L](ClO4)2.4H2O suitable for X-ray diffraction could be obtained and
      the crystalline structures are described. The interaction of L with Zn(2+) was
      investigated by potentiometry and UV-Vis showing the formation of mono- and
      dinuclear complexes involving the bipyridines. The macrocycle was used as a
      bridging ligand for the successful synthesis of a new dinuclear
      [(Ru(bpy)2)2(L)](PF6)4.4HPF6 complex that was fully characterized. The
      protonation (log K in the range 9.9-1.6) and coordination features of this
      compound towards Cu(2+) and Zn(2+) were explored by UV-Vis absorption and
      emission spectroscopies. 

PMID- 24305616
TI  - Mechanisms of leading edge protrusion in interstitial migration.
AB  - While the molecular and biophysical mechanisms underlying cell protrusion on two
      dimensional substrates are well understood, our knowledge of the actin structures
      driving protrusion in three-dimensional environments is poor, despite relevance
      to inflammation, development and cancer. Here we report that, during chemotactic
      migration through microchannels with 5 MUm * 5 MUm cross-sections, HL60
      neutrophil-like cells assemble an actin-rich slab filling the whole channel cross
      section at their front. This leading edge comprises two distinct F-actin
      networks: an adherent network that polymerizes perpendicular to cell-wall
      interfaces and a 'free' network that grows from the free membrane at the cell
      front. Each network is polymerized by a distinct nucleator and, due to their
      geometrical arrangement, the networks interact mechanically. On the basis of our
      experimental data, we propose that, during interstitial migration, medial growth
      of the adherent network compresses the free network preventing its retrograde
      movement and enabling new polymerization to be converted into forward protrusion.

PMID- 24305618
TI  - Molecular pathways: targeting resistance in the androgen receptor for therapeutic
      benefit.
AB  - Androgen receptor signaling is critical in the development and progression of
      prostate cancer, leading to intensive efforts to elucidate all potential points
      of inflection for therapeutic intervention. These efforts have revealed new
      mechanisms of resistance and raise the possibility that known mechanisms may
      become even more relevant in the context of effective androgen receptor
      suppression. These mechanisms include tumoral appropriation of alternative
      androgen sources, alterations in androgen receptor expression, androgen receptor
      mutations, truncated androgen receptor variants, alterations and cross-talk in
      recruitment of cofactors to androgen receptor binding sites in the genome, and
      androgen receptor-driven oncogenic gene fusions. New agents such as enzalutamide,
      EPI-001, androgen receptor-specific peptidomimetics, novel HSP90 inhibitors, and
      PARP inhibitors, as well as new approaches to cotargeting the androgen receptor
      pathway, point to the potential for more complete and durable control of androgen
      receptor-mediated growth.

PMID- 24305619
TI  - Lipid droplet-associated proteins (LDAPs) are involved in the
      compartmentalization of lipophilic compounds in plant cells.
AB  - While lipid droplets have traditionally been considered as inert sites for the
      storage of triacylglycerols and sterol esters, they are now recognized as dynamic
      and functionally diverse organelles involved in energy homeostasis, lipid
      signaling, and stress responses. Unlike most other organelles, lipid droplets are
      delineated by a half-unit membrane whose protein constituents are poorly
      understood, except in the specialized case of oleosins, which are associated with
      seed lipid droplets. Recently, we identified a new class of lipid-droplet
      associated proteins called LDAPs that localize specifically to the lipid droplet
      surface within plant cells and share extensive sequence similarity with the small
      rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we
      provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich
      fruit tissues, and further explore the functional relationships between LDAPs and
      SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays
      important roles in the compartmentalization of lipophilic compounds, including
      triacylglycerols and polyisoprenoids, into lipid droplets within plant cells.
      Potential roles in lipid droplet biogenesis and function of these proteins also
      are discussed. 

PMID- 24305620
TI  - Ovarian mucinous cystic tumor of borderline malignancy with a mural nodule of
      anaplastic spindle cell carcinoma: a case report.
AB  - Ovarian cystic tumors with a mural nodule are a rare entity. We report a case of
      a mural nodule of anaplastic spindle cell carcinoma in an ovarian mucinous cystic
      tumor of borderline malignancy. The patient was a 45-years-old Japanese woman who
      presented with an ovarian cyst. She suffered from mature cystic teratoma of both
      ovaries 9 years before the present history. Image analysis and laboratory data
      showing a high serum CA19-9 level suggested ovarian malignancy. She underwent
      bilateral salpingo-oophorectomy with hysterectomy and omentectomy. There was a
      mural nodule in the ovarian mucinous cystic lesion. Microscopically, the nodule
      was composed of spindle-shaped cells with severe nuclear atypia.
      Immunohistochemical analysis allowed the cells to be categorized as anaplastic
      spindle cell carcinoma. Fifteen months after the operation the patient is alive
      without any clinical findings of tumor recurrence. To the best of our knowledge
      in the English literature, this is the first report of a mural nodule of an
      anaplastic spindle cell carcinoma within an ovarian mucinous cystic borderline
      tumor harboring previously confirmed cystic teratoma. 

PMID- 24305621
TI  - C-reactive protein, APOE genotype and longitudinal cognitive change in an older
      population.
AB  - BACKGROUND: circulating measures of inflammatory markers, such as C-reactive
      protein (CRP) have been associated with an increased risk of future cognitive
      decline. However, the nature of the relationship among the very old (>75 years)
      is unclear. Cross-sectional evidence suggests that elevated CRP may even be
      protective in this age group. This study examines these associations
      longitudinally. METHODS: logistic regression was used to investigate the
      association between CRP and drop in cognitive performance (>=3 point change on
      the Mini-Mental State Examination) over a 4-year period in a population of 266
      people, mean age 77 years. RESULTS: increased levels of CRP were associated with
      a decreased risk of a drop in cognitive performance; however, this association
      was only seen in those without an APOE e4 allele [odds ratio of decline per unit
      increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained
      consistent after adjustment for cardiovascular confounders (smoking, drinking,
      MI, stroke, diabetes, education, medication and blood pressure). For those with
      an e4 allele, the relationship with longitudinal cognitive decline was neither
      statistically significant nor in a consistent direction after controlling for
      acute inflammation. CONCLUSIONS: this study strengthens previous cross-sectional
      findings and shows elevated levels of CRP to be linked to a decreased risk of
      longitudinal cognitive decline in the very old. However, as with prior analyses,
      this was only observed in those not carrying an APOE e4 allele. Future work on
      larger APOE e4 allele carrying samples is required to determine the nature of the
      association in this population.

PMID- 24305622
TI  - Yokukansan promotes hippocampal neurogenesis associated with the suppression of
      activated microglia in Gunn rat.
AB  - BACKGROUND: The pathophysiology of schizophrenia (SCZ) remains unclear, and its
      treatment is far from ideal. We have previously reported that yokukansan (YKS),
      which is a traditional Japanese medicine, is effective as an adjunctive therapy
      for SCZ. However, the mechanisms underlying the action of YKS have not yet been
      completely elucidated. A recent meta-analysis study has shown that adjuvant anti
      inflammatory drugs are effective for SCZ treatment, and it has been proposed that
      some of the cognitive deficits associated with inflammation may in part be
      related to inflammation-induced reductions in adult hippocampal neurogenesis.
      Although certain ingredients of YKS have potent anti-inflammatory activity, no
      study has determined if YKS has anti-inflammatory properties. METHODS: Using the
      Gunn rat, which has been reported as a possible animal model of SCZ, we
      investigated whether YKS affects cognitive dysfunction in an object-location test
      and the suppression of microglial activation and neurogenesis in the hippocampus.
      RESULTS: We found that YKS ameliorated spatial working memory in the Gunn rats.
      Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the
      hippocampal dentate gyrus of these rats. These results suggest that the
      ameliorative effects of YKS on cognitive deficits may be mediated in part by the
      suppression of the inflammatory activation of microglia. CONCLUSIONS: These
      findings shed light on the possible mechanism underlying the efficacy of YKS in
      treating SCZ.

PMID- 24305623
TI  - Therapeutic effects of multifunctional tetramethylpyrazine nitrone on models of
      Parkinson's disease in vitro and in vivo.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease.
      Although the etiology of PD is not completely understood, it is well-documented
      that oxidative stress and Ca(2+)-mediated cellular damage play important roles in
      the progression of PD. 2-[[(1,1-Dimethylethyl)oxidoimino]-methyl]-3,5,6
      trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has
      shown significant therapeutic effects in stroke models due to its multiple
      functions, including calcium overload blockade and free radical-scavenging. In
      this study, we investigated the neuroprotective and neurorescue effects of TBN on
      various in vitro and in vivo models of PD and explored its possible mechanisms of
      action. The results show that TBN exerted significant neuroprotection on 1-methyl
      4-phenylpyridinium (MPP(+))-induced damage in SH-SY5Y cells and primary
      dopaminergic neurons, as well as on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-induced dopaminergic neuron loss in zebrafish (TBN and MPTP were added
      simultaneously into the fish embryo medium and the treatment period was 48 h). In
      the MPTP-induced mouse and 6-hydroxydopamine (6-OHDA)-induced rat PD models, TBN
      administrated orally twice daily for 14 d (3 d post-MPTP lesion in mice and 7 d
      post-6-OHDA lesion in rats) exhibited remarkable neurorescue effects to increase
      the number of dopaminergic neurons. In addition, TBN improved apomorphine-induced
      rotational behavior in the 6-OHDA-lesioned PD rats. TBN suppressed the MPP(+)
      induced intracellular reactive oxygen species (ROS) in SH-SY5Y cells, increased
      the superoxide dismutase (SOD) activity and glutathione (GSH) concentration in
      the substantial nigra of MPTP-treated mice. These data indicate that TBN protects
      and rescues dopaminergic neurons from MPP(+) and MPTP/6-OHDA-induced damage by
      reducing ROS and increasing cellular antioxidative defense capability. 

PMID- 24305625
TI  - Nevirapine concentrations in saliva measured by thin layer chromatography and
      self-reported adherence in patients on antiretroviral therapy at Kilimanjaro
      Christian Medical Centre, Tanzania.
AB  - BACKGROUND: Thin layer chromatography (TLC) can be used to perform therapeutic
      drug monitoring in resource-limited settings, where more expensive analytical
      methods, such as high-performance liquid chromatography or liquid chromatography
      mass spectrometry, are not feasible. OBJECTIVES: The aim of this cross-sectional
      study was to compare saliva concentrations of nevirapine (NVP) with self-reported
      adherence in patients on NVP-containing antiretroviral treatment at Kilimanjaro
      Christian Medical Centre, Moshi, Tanzania. METHODS: HIV-infected patients using a
      combination of zidovudine + lamivudine + NVP, or stavudine + lamivudine + NVP,
      for more than 4 weeks were included. Saliva samples were collected using dental
      cotton rolls impregnated with citric acid (20 mg). Saliva NVP concentrations were
      analyzed using TLC. Adherence to ARV medication was assessed by self-reporting
      using the Morisky scale. RESULTS: Of the 91 study participants, 79 (86.8%) had
      therapeutic saliva NVP concentrations (ie, >1.75 mg/L) and 12 (13.2%) had
      subtherapeutic concentrations. Self-reported adherence among the study
      participants was high in 62 participants (68.1%), moderate in 24 (26.4%), and low
      in 5 (5.5%). Fifty-seven (91.9%) of the study participants with high self
      reported adherence had therapeutic saliva NVP concentrations. Of the 5
      participants with low self-reported adherence, 3 had therapeutic NVP
      concentrations. CONCLUSIONS: A high proportion of patients had therapeutic NVP
      saliva concentrations as measured by TLC, which showed a good agreement with self
      reported adherence.

PMID- 24305624
TI  - Floral advertisement scent in a changing plant-pollinators market.
AB  - Plant-pollinator systems may be considered as biological markets in which
      pollinators choose between different flowers that advertise their nectar/pollen
      rewards. Although expected to play a major role in structuring plant-pollinator
      interactions, community-wide patterns of flower scent signals remain largely
      unexplored. Here we show for the first time that scent advertisement is higher in
      plant species that bloom early in the flowering period when pollinators are
      scarce relative to flowers than in species blooming later in the season when
      there is a surplus of pollinators relative to flowers. We also show that less
      abundant flowering species that may compete with dominant species for pollinator
      visitation early in the flowering period emit much higher proportions of the
      generalist attractant beta-ocimene. Overall, we provide a first community-wide
      description of the key role of seasonal dynamics of plant-specific flower scent
      emissions, and reveal the coexistence of contrasting plant signaling strategies
      in a plant-pollinator market. 

PMID- 24305626
TI  - Optimal sparse sampling for estimating ganciclovir/valganciclovir AUC in solid
      organ transplant patients using NONMEN.
AB  - BACKGROUND: Ganciclovir and valganciclovir (GCV/VGCV) are used for the treatment
      and prophylaxis of cytomegalovirus in solid organ transplant (SOT) patients. An
      area under the time-concentration curve of 40-50 MUg * h/mL is related to
      efficacy. Therapeutic drug monitoring could prevent suboptimal drug exposure and
      adverse events, but obtaining full concentration profiles is not feasible.
      Sampling optimization by developing a reliable and clinically applicable limited
      sampling strategy (LSS) may simplify dose adjustment. METHODS: An LSS was
      developed using an original pharmacokinetic (PK) data set of 40 full profiles
      from 20 adult SOT patients. The LSS was developed based on population and
      Bayesian prediction approaches. Population PK parameters from a previous model
      were used for simulation or as priors (NONMEM version 7.2). Median percentage of
      prediction error and median of absolute percentage prediction error were
      calculated for plasma clearance (CL) and central compartment distribution volume
      (V(2)). Bias and precisions were compared using 1-way analysis of variance
      (SPSSv19.0). RESULTS: Sampling windows were designed according to the PK profile
      previously observed with the entire set of data. The 4 windows selected were
      distributed from 0.5 to 1.5 hours, 2 to 3 hours, 4 to 5 hours, and 6 to 8 hours.
      Predose and concentrations beyond 8 hours were not considered in any case because
      simulated negative concentrations occurred in both cases. Predicted exposure
      using 3 sampling times (0.5-1.5, 4-5, and 6-8 hours) showed the best predictive
      performance, by either the population or Bayesian approaches. Bias and
      imprecision for CL and V(2) were 0 and 0.60%, and -0.78% and 0.78%, respectively.
      CONCLUSIONS: GCV/VCG area under the time-concentration curve in SOT patients
      could be predicted with acceptable accuracy for clinical management and dose
      individualization using LSS. The estimator of GCV/VGC, using 3 concentrations
      measured at 0.5-1.5, 4-5, and 6-8 hours after drug intake, could be used for dose
      adjustment.

PMID- 24305627
TI  - Plasma concentrations of tyrosine kinase inhibitors imatinib, erlotinib, and
      sunitinib in routine clinical outpatient cancer care.
AB  - BACKGROUND: The objectives of this study were to evaluate the plasma
      concentrations of the tyrosine kinase inhibitors (TKIs), imatinib, erlotinib, and
      sunitinib, in a cohort of patients with cancer in routine clinical practice and
      to find the possible factors related to plasma concentrations below the target
      level. METHODS: An observational study was performed in an unselected cohort of
      patients using TKIs for cancer treatment. Randomly timed plasma samples were
      drawn together with regular laboratory investigations during routine outpatient
      clinic visits. The plasma concentrations of TKIs were determined using a
      validated high-performance liquid chromatography coupled with tandem mass
      spectrometry detection method. Trough concentrations were estimated using the
      interval between the last dose intake and blood sampling and the mean elimination
      half-life of the TKIs and were compared with target trough concentrations.
      Outpatient medical records were reviewed to collect data on patient- and
      medication-related factors that could have contributed to the variation in TKI
      plasma concentrations. RESULTS: Only 26.8%, 88.9%, and 51.4% of the calculated
      trough plasma concentrations of imatinib, erlotinib, and sunitinib samples,
      respectively, reached the predefined target concentration (imatinib: 1100 ng/mL,
      erlotinib: 500 ng/mL, and sunitinib: 50 ng/mL). Interpatient variability was high
      with coefficients of variation of 39.1%, 40.1%, and 29.2% for imatinib,
      erlotinib, and sunitinib, respectively. High variation in plasma concentrations
      could only partly be explained by patient- or medication related factors.
      CONCLUSIONS: Almost half of the plasma concentrations in the outpatient
      population seemed to be below the target level with a risk of treatment failure.
      It is not possible to predict which patients are at a risk of plasma
      concentrations below the target level based on patient- or medication-related
      factors. Thus, therapeutic drug monitoring could play a crucial role in routine
      cancer care to identify patients that are in need of individual adjusted dosages.
      Further research is required to investigate the safety and efficacy of
      therapeutic drug monitoring.

PMID- 24305628
TI  - Low but inducible contribution of renal elimination to clearance of propylene
      glycol in preterm and term neonates.
AB  - BACKGROUND: Despite limited information being available on the pharmacokinetics
      of excipients, propylene glycol (PG) is often used as an excipient in both adults
      and children. The aim of this study is to characterize the renal and hepatic
      elimination of PG in preterm and term neonates. METHODS: The pharmacokinetic
      analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in
      plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight
      630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG
      coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours),
      phenobarbital (5 mg.kg(-1).d(-1)), or both. To capture the time-dependent trend
      in the renal excretion of PG, different models based on time after the first
      dose, urine volume, and creatinine amount in urine were tested. RESULTS: A one
      compartment model parameterized in terms of renal clearance, hepatic clearance,
      and volume of distribution was found to adequately describe the observations in
      both plasma and urine. After the first dose was administered, the renal
      elimination of PG was 15% of total clearance, which increased over time to 25% at
      24 hours after the first dose of PG. This increase was best described using a
      hyperbolic function based on time after the first dose. CONCLUSIONS: Renal
      elimination of PG in (pre)term neonates is low, particularly compared with the
      reported percentage of 45% in adults, but it may increase with time after the
      first dose of PG. To study whether this increase is caused by an autoinduced
      increase in the renal secretion or a reduction of tubular reabsorption of PG,
      further research is needed.

PMID- 24305629
TI  - A direct method for the measurement of everolimus and sirolimus in whole blood by
      LC-MS/MS using an isotopic everolimus internal standard.
AB  - BACKGROUND: Whole-blood concentrations of the immunosuppressant drugs everolimus
      and sirolimus should be monitored. A sensitive and selective method offering the
      detection of both analytes in small sample volumes would optimize the throughput
      of samples for sirolimus or everolimus analysis. This study reports the
      validation of a liquid chromatography tandem mass spectrometry method, including
      a stable isotope internal standard, for the simultaneous measurement of
      everolimus and sirolimus. METHODS: Whole-blood samples (20 MUL) were treated with
      ammonium bicarbonate (20 MUL), zinc sulfate (20 MUL), and internal standard
      solution ((13)C(2)D(4)-everolimus in acetonitrile, 100 MUL). After
      centrifugation, 20 MUL of the supernatant was injected onto a Waters Symmetry C18
      high-performance liquid chromatography column. The aqueous and organic mobile
      phases were 2 mmole/L of ammonium acetate containing 0.1% (vol/vol) formic acid,
      in water and methanol, respectively. Analytes were detected using tandem mass
      spectrometry (Waters Acquity TQD). RESULTS: Analytes were eluted at around 2
      minutes within a 6-minute analytical run time. Detector response was linear for
      both analytes across the ranges studied (1-49 MUg/L for sirolimus, 1-41 MUg/L for
      everolimus), and a lower limit of quantitation of 1 MUg/L was reliably attained.
      Intraassay and interassay imprecision and inaccuracy were <15% (coefficient of
      variation) in all cases. Analyte recovery was in the range of 72%-117%. The
      analytes were stable in blood after freezing and thawing, and for at least 12
      hours after preparation while waiting to be injected. Ion suppression and
      interference from phospholipids were not significant. CONCLUSIONS: A
      straightforward, robust liquid chromatography tandem mass spectrometry assay has
      been developed and validated for the simultaneous measurement of everolimus and
      sirolimus in small volumes of whole blood.

PMID- 24305630
TI  - Evaluation of Plasmodium falciparum gametocyte detection in different patient
      material.
AB  - BACKGROUND: For future eradication strategies of malaria it is important to
      control the transmission of gametocytes from humans to the anopheline vector
      which causes the spread of the disease. Sensitive, non-invasive methods to detect
      gametocytes under field conditions can play a role in monitoring transmission
      potential. METHODS: Microscopically Plasmodium falciparum-positive patients from
      Jimma, Ethiopia donated finger-prick blood, venous blood, saliva, oral mucosa and
      urine samples that were spotted on filter paper or swabs. All samples were taken
      and stored under equal, standardized conditions. RNA was extracted from the
      filter paper and detected by real-time QT-NASBA. Pfs16-mRNA and Pfs25-mRNA were
      measured with a time to positivity to detect gametocyte specific mRNA in
      different gametocyte stages. They were compared to 18S-rRNA, which is expressed
      in all parasite stages. Results were quantified via a known dilution series of
      artificial RNA copies. RESULTS: Ninety-six samples of 16 uncomplicated malaria
      patients were investigated. 10 (66.7%) of the slides showed gametocyte densities
      between 0.3-2.9 gametocytes/MUl. For all RNA-targets, molecular detection in
      blood samples was most sensitive; finger-prick sampling required significantly
      smaller amounts of blood than venous blood collection. Detection of asexual 18S
      rRNA in saliva and urine showed sensitivities of 80 and 67%, respectively. Non
      invasive methods to count gametocytes proved insensitive. Pfs16-mRNA was
      detectable in 20% of urine samples, sensitivities for other materials were lower.
      Pfs25-mRNA was not detectable in any sample. CONCLUSIONS: The sensitivity of non
      invasively collected material such as urine, saliva or mucosa seems unsuitable
      for the detection of gametocyte-specific mRNA. Sensitivity in asymptomatic
      carriers might be generally even lower. Finger-prick testing revealed the highest
      absolute count of RNA copies per MUL, especially for Pfs25-mRNA copies. The
      method proved to be the most effective and should preferably be applied in future
      transmission control and eradication plans. A rapid test for gametocyte targets
      would simplify efforts.

PMID- 24305631
TI  - Florigen is involved in axillary bud development at multiple stages in
      Arabidopsis.
AB  - The wide variety of plant architectures is largely based on diverse and flexible
      modes of axillary shoot development. In Arabidopsis, floral transition
      (flowering) stimulates axillary bud development. The mechanism that links
      flowering and axillary bud development is, however, largely unknown. We recently
      showed that FLOWERING LOCUS T (FT) protein, which acts as florigen, promotes the
      phase transition of axillary meristems, whereas BRANCHED1 (BRC1) antagonizes the
      florigen action in axillary buds. Here, we present evidences for another possible
      role of florigen in axillary bud development. Ectopic overexpression of FT or
      another florigen gene TWIN SISTER OF FT (TSF) with LEAFY (LFY) induces ectopic
      buds at cotyledonary axils, confirming the previous proposal that these genes are
      involved in formation of axillary buds. Taken together with our previous report
      that florigen promotes axillary shoot elongation, we propose that florigen
      regulates axillary bud development at multiple stages to coordinate it with
      flowering in Arabidopsis. 

PMID- 24305632
TI  - P-gp expression in brown trout erythrocytes: evidence of a detoxification
      mechanism in fish erythrocytes.
AB  - Blood is a site of physiological transport for a great variety of molecules,
      including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are
      directly exposed to aquatic pollution. P-gp are ubiquitous "membrane
      detoxification proteins" implicated in the cellular efflux of various
      xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be
      pollutants. The existence of this P-gp detoxification system inducible by benzo
      [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated
      erythrocytes of brown trout. Western blot analysis showed the expression of a 140
      kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to
      increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the
      same BaP-treated erythrocytes, P-gp expression increased significantly in a dose
      dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism
      against the pollutant, a property that can be exploited for future biomarker
      development to monitor water quality. 

PMID- 24305633
TI  - Differences in negative T waves between acute pulmonary embolism and acute
      coronary syndrome.
AB  - BACKGROUND: Patients with acute pulmonary embolism (APE) often have negative T
      waves (Neg T) in precordial leads at presentation, but this is also found in
      acute coronary syndrome (ACS) caused by left anterior descending coronary artery
      (LAD) disease. METHODS AND RESULTS: Differences in Neg T on admission
      electrocardiograms were studied between 107 patients with APE and 248 patients
      with ACS caused by LAD disease. All patients had Neg T in leads V1-4 and were
      admitted within 7 days from symptom onset. The number of leads with Neg T (4.8+/
      1.8 vs. 5.5+/-1.7, P<0.001) and maximum magnitude of Neg T (3.4+/-2.0 vs. 4.7+/
      3.3mm, P<0.001) were lower in APE. The frequency of occurrence of Neg T in each
      of the 12 leads, and the precordial lead with the greatest Neg T (peak Neg T)
      differed between APE and ACS (all P<0.05, respectively). APE was strongly
      associated with the presence of Neg T in both leads III and V1 and peak Neg T in
      leads V1-2. The combination of these 2 findings identified APE with 98%
      sensitivity, 92% specificity, and 94% predictive accuracy, which represented the
      highest diagnostic accuracy. CONCLUSIONS: Among patients with APE and ACS who
      have precordial Neg T, the presence of Neg T in leads III and V1 and/or peak Neg
      T in leads V1-2 simply but accurately differentiates APE from ACS.  

PMID- 24305634
TI  - Mechanisms of exercise intolerance in heart failure with preserved ejection
      fraction.
AB  - Approximately half of patients with heart failure (HF) have a preserved ejection
      fraction (HFpEF), and with the changing age and comorbidity characteristics in
      the adult population, this number is growing rapidly. The defining symptom of
      HFpEF is exercise intolerance, but the specific mechanisms causing this common
      symptom remain debated and inadequately understood. Although diastolic
      dysfunction was previously considered to be the sole contributor to exercise
      limitation, recent studies have identified the importance of ventricular
      systolic, chronotropic, vascular, endothelial and peripheral factors that all
      contribute in a complex and highly integrated fashion to produce the signs and
      symptoms of HF. This review will explore the mechanisms underlying objective and
      subjective exercise intolerance in patients with HFpEF.

PMID- 24305636
TI  - Nanomedicine: de novo design of nanodrugs.
AB  - Phenomenal advances in nanotechnology and nanoscience have been accompanied by
      exciting progress in de novo design of nanomedicines. Nanoparticles with their
      large space of structural amenability and excellent mechanical and electrical
      properties have become ideal candidates for high efficacy nanomedicines in both
      diagnostics and therapeutics. The therapeutic nanomedicines can be further
      categorized into nanocarriers for conventional drugs and nanodrugs with direct
      curing of target diseases. Here we review some of the recent advances in de novo
      design of nanodrugs, with an emphasis on the molecular level understanding of
      their interactions with biological systems including key proteins and cell
      membranes. We also include some of the latest advances in the development of
      nanocarriers with both passive and active targeting for completeness. These
      studies may shed light on a better understanding of the molecular mechanisms
      behind these nanodrugs, and also provide new insights and direction for the
      future design of nanomedicines. 

PMID- 24305637
TI  - Pretransplant Aspergillus colonization of cystic fibrosis patients and the
      incidence of post-lung transplant invasive aspergillosis.
AB  - BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and
      mortality among patients undergoing lung transplant. Cystic fibrosis-lung
      transplant recipients (CF-LTRs) may be at greater risk of IA following lung
      transplantation because of the presence of Aspergillus in their airways before
      transplantation. This study evaluated the impact of pretransplant Aspergillus
      colonization on the risk for IA among CF-LTRs. METHODS: A single-center
      retrospective cohort study of CF-LTRs was conducted between 2006 and 2010.
      Respiratory tract cultures before transplantation were reviewed to identify
      patients with pretransplant Aspergillus colonization. Patients with positive
      Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL)
      galactomannan after transplantation were classified as having colonization or
      disease according to the International Society of Heart and Lung Transplantation
      criteria. RESULTS: A total of 93 CF patients underwent lung transplantation.
      Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization.
      Thirty-six patients had positive intraoperative Aspergillus culture from the
      native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to
      IA was 42 days following transplantation. Positive intraoperative Aspergillus
      culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular
      rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15,
      P=0.05) were independent risk factors for IA. Antifungal prophylaxis was
      administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93).
      IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06,
      P=0.23). CONCLUSION: Pretransplant Aspergillus colonization is frequent among CF
      LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher
      risk of developing IA.

PMID- 24305638
TI  - Effects of simultaneous iliac artery angioplasty on graft and patient survival
      after living-donor kidney transplantation.
AB  - BACKGROUND: Renal transplant candidates with extended indications, such as older
      age and advanced atherosclerosis, are currently accepted onto the waiting list.
      METHODS: We retrospectively evaluated the clinical outcomes of simultaneous
      kidney transplantation and angioplasty compared with transplantation alone.
      RESULTS: We included 748 patients who underwent living-donor kidney transplant
      because of end-stage renal disease during a 5-year period, consisting of 27
      kidney transplants with simultaneous angioplasty and 721 without additional
      vascular procedures. As candidates for simultaneous angioplasty and transplant,
      we considered patients with TransAtlantic Inter-Society Consensus type A and B
      aorto-iliac disease. We compared transplant outcomes in patients who did or did
      not receive simultaneous angioplasty. Although simultaneous iliac artery
      angioplasty was significantly related to recipient age, diabetes mellitus,
      hypertension, and coronary artery disease, it was not associated with graft
      (uncensored, P=0.937; death censored, P=0.981) or patient (P=0.804) survival
      during the follow-up period. In addition, simultaneous angioplasty was not
      associated with a higher risk of delayed graft function (P=0.099) or a longer
      hospital stay (P=0.790). There was no significant difference in mortality due to
      a cardiovascular event between the two groups (P=0.199). CONCLUSIONS:
      Simultaneous iliac artery angioplasty and kidney transplantation in carefully
      selected patients can be performed safely with equivalent graft and patient
      survival to transplantation alone.

PMID- 24305639
TI  - Ureteral complications after hand-assisted laparoscopic living donor nephrectomy.
AB  - BACKGROUND: Urological complications, namely ureteral leak and obstruction,
      remain a major source of morbidity after renal transplantation. Given that the
      existing literature on ureteral complications pertains mostly to deceased as
      opposed to living donors, we aimed to assess the risk factors for ureteral
      complications solely after living donor nephrectomy. METHODS: We identified 480
      consecutive cases of renal transplantation after hand-assisted laparoscopic
      living donor nephrectomy at our institution from January 2008 to February 2013.
      We determined the incidence of ureteral complications and assessed the
      association with a number of perioperative factors, including age, sex, race, and
      body mass index of both the donor and recipient; arterial and ureteral anatomy;
      procurement by transplant surgeon versus urologist; history of previous renal
      transplantations; technique of ureteral anastomosis; use of ureteral stent; total
      ischemia time; serum creatinine on discharge; and need for temporary
      posttransplant hemodialysis. RESULTS: Among 480 renal transplantations after
      living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including
      ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors
      were significantly associated with ureteral complications on multivariate
      analysis: increased donor age and no placement of ureteral stent. CONCLUSIONS:
      Ureteral complications of renal transplants after living donor nephrectomy are
      uncommon. The use of a ureteral stent is protective against ureteral
      complications and increased donor age is associated with an increased incidence
      of ureteral complications.

PMID- 24305640
TI  - Phase transition and band-structure tuning in InN through uniaxial and biaxial
      strains.
AB  - The phase transitions and band structure of InN under uniaxial and biaxial
      strains are systematically investigated using first-principles calculations. The
      main findings are summarized as follows: (I) although graphite-like phases are
      observed for both types of strain, the phase transitions are drastically
      different: second order for uniaxial strain and first order for biaxial strain.
      Furthermore, the second-order transition is driven by elastic and dynamical
      instabilities, whereas the first-order transition is driven only by elastic
      instability. (II) The wurtzite bandgap is always direct and that of the graphite
      like phase is always indirect. Furthermore, the wurtzite bandgap is drastically
      enhanced by compressive uniaxial strain but reduced by tensile uniaxial strain.
      However, both biaxial strains greatly reduce the bandgap and eventually the semi
      metallic phases are achieved.

PMID- 24305642
TI  - Knowledge is not power for patients: a systematic review and thematic synthesis
      of patient-reported barriers and facilitators to shared decision making.
AB  - OBJECTIVE: To systematically review patient-reported barriers and facilitators to
      shared decision making (SDM) and develop a taxonomy of patient-reported barriers.
      METHODS: Systematic review and thematic synthesis. Study findings/results for
      each included paper were extracted verbatim and entered into qualitative software
      for inductive analysis. RESULTS: Electronic and follow-up searches yielded 2956
      unique references; 289 full-text articles were retrieved, of which 45 articles
      from 44 unique studies met inclusion criteria. Key descriptive themes were
      grouped under two broad analytical themes: how the healthcare system is organized
      (4 descriptive themes) and what happens during the decision-making interaction (4
      descriptive themes, 10 sub-themes). Predominant emergent themes related to
      patients' knowledge and the power imbalance in the doctor-patient relationship.
      Patients need knowledge and power to participate in SDM - knowledge alone is
      insufficient and power is more difficult to attain. CONCLUSION: Many barriers are
      potentially modifiable, and can be addressed by attitudinal changes at the levels
      of patient, clinician/healthcare team, and the organization. The results support
      the view that many patients currently can't participate in SDM, rather than they
      won't participate because they do not want to. PRACTICE IMPLICATIONS: Future
      implementation efforts should address patient-reported factors together with
      known clinician-reported barriers and the wider organizational context.

PMID- 24305643
TI  - Functional impact of a spectrum of interstitial lung abnormalities in rheumatoid
      arthritis.
AB  - BACKGROUND: Approximately 10% of patients with rheumatoid arthritis (RA) have
      interstitial lung disease (ILD), and one-third have subclinical ILD on chest CT
      scan. In this study, we aimed to further characterize functional decrements in a
      spectrum of RA-associated ILD. METHODS: All subjects were enrolled in the Brigham
      and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). The presence
      of interstitial lung abnormalities (ILAs) on clinically indicated chest CT scans
      was determined using a previously validated sequential reading method. Univariate
      and multivariate analyses were used to assess the association between degree of
      ILAs and physiologic, functional, and demographic variables of interest. RESULTS:
      Of 1,145 BRASS subjects, 91 subjects (8%) were included in this study. Twelve had
      radiologically severe ILAs, 34 had ILAs, and 38 had no ILAs on CT scan. Subjects
      with radiologically severe ILAs were older (P = .0037), had increased respiratory
      symptoms (cough, P = .027; dyspnea, P = .010), and more severe RA disease
      (rheumatoid factor, P = .018; total swollen joints, P = .046) compared with
      subjects with no ILAs. Participants also had a trend toward having an increased
      smoking history (P = .16) and having lower FVC % predicted (77% vs 94%, P = .097)
      and diffusion capacity of carbon monoxide % predicted (52% vs 77%, P = .068).
      Similar but attenuated increases in respiratory symptoms, functional decrements,
      and RA disease severity were observed in subjects with ILAs compared with those
      with no ILAs. CONCLUSIONS: We have shown that patients with RA have varying
      degrees of ILAs that are associated with a spectrum of functional and physiologic
      decrements. Our findings suggest that improved risk stratification and detection
      of ILAs will provide a therapeutic window that could improve RA-ILD outcomes.

PMID- 24305645
TI  - Bilateral bispectral index monitoring during and after electroconvulsive therapy
      compared with magnetic seizure therapy for treatment-resistant depression.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective and established
      treatment for depression. Magnetic seizure therapy (MST) has recently been
      developed and seems equally effective while associated with fewer side-effects.
      Both require general anaesthesia, which could be quantified using the bispectral
      index (BIS). We compared ECT and MST with respect to recovery times, left-sided
      BIS, and left-right differences in BIS. METHODS: In this prospective,
      observational study, we enrolled 10 successive patients receiving ECT and 10
      patients undergoing MST. Anaesthesia was performed with propofol and monitored
      with a bilateral BIS sensor. The seizure was elicited when the BIS was within a
      range from 50 to 60. The time to eye opening was measured and bilateral BIS were
      recorded for 10 min after seizure induction. RESULTS: A comparable anaesthetic
      depth was observed in the ECT and MST groups at baseline [mean (standard
      deviation, sd) BIS values of 94.1 (4.1) and 95.5 (3.0), respectively] and before
      seizure induction [mean (sd) BIS values of 52.3 (9.6) and 55.2 (10.3),
      respectively]. Post-ictally, MST patients opened their eyes significantly earlier
      than ECT patients [3.0 (1.0) vs 6.7 (1.3) min, P<0.001]. They showed a
      significantly higher BIS at 2 min after seizure induction [69.2 (10.1) vs 50.9
      (15.9), P=0.003], and this difference was still present at 10 min after seizure
      induction [BIS 81.5 (6.5) vs 68.0 (16.4), P<0.001]. Significant differences
      between the left and right BIS were observed in neither the ECT nor the MST
      group. CONCLUSIONS: At a comparable anaesthetic depth, MST is superior to ECT in
      terms of post-ictal recovery, which is correctly reflected by higher post-ictal
      BIS values. Unilateral BIS monitoring is sufficient to monitor anaesthetic depth
      in ECT and MST patients. TRIAL REGISTRY NUMBER: NCT 01318018.

PMID- 24305644
TI  - KaiC intersubunit communication facilitates robustness of circadian rhythms in
      cyanobacteria.
AB  - The cyanobacterial circadian clock is the only model clock to have been
      reconstituted in vitro. KaiC, the central clock component, is a homohexameric
      ATPase with autokinase and autophosphatase activities. Changes in phosphorylation
      state have been proposed to switch KaiC's activity between autokinase and
      autophosphatase. Here we analyse the molecular mechanism underlying the
      regulation of KaiC's activity, in the context of its hexameric structure. We
      reconstitute KaiC hexamers containing different variant protomers, and measure
      their autophosphatase and autokinase activities. We identify two types of
      regulatory mechanisms with distinct functions. First, local interactions between
      adjacent phosphorylation sites regulate KaiC's activities, coupling the ATPase
      and nucleotide-binding states at subunit interfaces of the CII domain. Second,
      the phosphorylation states of the protomers affect the overall activity of KaiC
      hexamers via intersubunit communication. Our findings indicate that intra
      hexameric interactions play an important role in sustaining robust circadian
      rhythmicity. 

PMID- 24305646
TI  - Impact of anaesthetic drugs and adjuvants on ECG markers of torsadogenicity.
AB  - Drug-induced prolongation of cardiac repolarization may trigger malignant
      ventricular arrhythmias, such as torsade de pointes. The duration of QT interval,
      QT corrected for heart rate (QTc), JT interval, QT dispersion (QTd), QT
      variability index, and transmular dispersion of repolarization (TDR) are ECG
      markers of torsadogenicity. All volatiles, especially isoflurane and desflurane,
      have been found to prolong QTc and QTcd, while sevoflurane has probably no
      effects on TDR. Among i.v. anaesthetics, propofol seems superior due to its
      minimal effects on QTc and TDR; moreover, a decrease in QTc and QTcd has been
      demonstrated in many studies. Regarding opioids, fentanyl, alfentanil, and
      remifentanil produce no effects on QTc, while sufentanil, at high doses, may
      induce QT prolongation. Succinylcholine, but not the non-depolarizing
      neuromuscular blockers, produces QTc prolongation which can be attenuated by
      opioids and beta-blockers. Reversal of neuromuscular block with
      anticholinesterase-anticholinergic combinations has been associated with
      significant QTc prolongation, while such an effect has not been demonstrated for
      sugammadex, even at high doses. Local anaesthetics have probably no intrinsic
      action on duration of repolarization; nevertheless, an extensive subarachnoid
      sympathetic block may increase the duration of QTc. On the contrary, thoracic
      epidural anaesthesia has been associated with a decrease in both QTc and TDR.
      Among adjuvants, midazolam seems to have no effect on QTc and TDR, while commonly
      used antiemetics, such as droperidol, domperidone, and most 5-HT3 antagonists,
      produce significant QT prolongation. The effects of anaesthetic drugs and
      techniques on electrocardiographic torsadogenic markers should be considered in
      the perioperative management of patients with preexisting repolarization
      abnormalities. 

PMID- 24305647
TI  - Initial glomerular filtration rate and survival in hemodialysis. The role of
      permanent vascular access.
AB  - BACKGROUND: A significant increase in the number of patients starting chronic
      hemodialysis (HD) with an estimated glomerular filtration rate (eGFR)>=10
      mL/min/1.73 m(2) was observed in Argentina between 2004 and 2009. METHODS: In
      order to study this topic, we calculated the mortality hazard ratios (HR) in a
      cohort of incident HD individuals from the Argentine Registry of Chronic Dialysis
      [Registro Argentino de Dialisis Cronica] (2004-2009), grouped according to the
      initial eGFR (0-4.9, 5-9.9, 10-14.9 and >=15 mL/min/1.73 m(2) ; reference group 0
      4.9) estimated by CKD-EPI; in three cohorts: "total population", "healthy" (<65
      years, without diabetes or comorbidities) and "planned entry" (with permanent
      vascular access). RESULTS: After adjusting the population (n=16,931) for age,
      gender, coexisting conditions, serum albumin, income, and temporary vascular
      access a HR of 1.19 (95%CI:1.07-1.33) was observed in the group with eGFR>=15
      mL/min/1.73 m(2). In the cohort of 3,897 "healthy" after adjusting for the same
      co-variates, HRs of 1.44 (95%CI: 1.08-1.65) and 1.65 (95%CI: 1.06-2.55) were
      obtained for the groups with baseline eGFR values of 10-14.9 and >=15 mL/min/1.73
      m(2), respectively. In "planned entry" patients (n=6,280), after adjusting for
      age, gender, co-morbidities, serum albumin and income, HRs in all groups were not
      significantly different as compared to the control group. CONCLUSIONS: HD
      initiation with eGFR>10 mL/min/1.73 m(2) shows no survival advantage. The higher
      mortality in the group with >eGFR starting dialysis looks like an "artifact"
      related to higher age, more co-morbidities, low albuminemia and the use of
      temporary vascular access.

PMID- 24305648
TI  - Anterior cruciate ligament tears in children and adolescents: a meta-analysis of
      nonoperative versus operative treatment.
AB  - BACKGROUND: Debate regarding the optimal initial treatment for anterior cruciate
      ligament (ACL) injuries in children and adolescents has not resulted in a clear
      consensus for initial nonoperative treatment or operative reconstruction.
      HYPOTHESIS/PURPOSE: The purpose of this meta-analysis was to systematically
      analyze aggregated data from the literature to determine if a benefit exists for
      either nonoperative or early operative treatment for ACL injuries in the
      pediatric patient. The hypothesis was that combined results would favor early
      operative reconstruction with respect to posttreatment episodes of
      instability/pathological laxity, symptomatic meniscal tears, clinical outcome
      scores, and return to activity. STUDY DESIGN: Meta-analysis. METHODS: A
      literature selection process included the extraction of data on the following
      clinical variables: symptomatic meniscal tears, return to activities, clinical
      outcome scores, return to the operating room, and posttreatment
      instability/pathological laxity. A symptomatic meniscal tear was defined as
      occurring after the initial presentation, limiting activity, and requiring
      further treatment. Instability/pathological laxity was defined for the sake of
      this study as having an episode of giving way, a grade >=2 Lachman/pivot-shift
      test result, or a side-to-side difference of >4 mm as measured by the KT-1000
      arthrometer. All studies were evaluated using a formal study quality analysis.
      Meta-analysis was conducted for aggregated data in each category. RESULTS: Six
      studies (217 patients) comparing operative to nonoperative treatment and 5
      studies (353 patients) comparing early to delayed reconstruction were identified.
      Three studies reported posttreatment instability/pathological laxity; 13.6% of
      patients after operative treatment experienced instability/pathological laxity
      compared with 75% of patients after nonoperative treatment (P < .01). Two studies
      reported symptomatic meniscal tears; patients were over 12 times more likely to
      have a medial meniscal tear after nonoperative treatment than after operative
      treatment (35.4% vs 3.9%, respectively; P = .02). A significant difference in
      scores between groups was noted in 1 of 2 studies reporting International Knee
      Documentation Committee (IKDC) scores (P = .002) and in 1 of 2 studies reporting
      Tegner scores (P = .007). Two studies reported return to activity; none of the
      patients in the nonoperative groups returned to their previous level of play
      compared with 85.7% of patients in the operative groups (P < .01). Study quality
      analysis revealed that the majority of the studies were inconsistent in reporting
      outcomes. CONCLUSION: Meta-analysis revealed multiple trends that favor early
      surgical stabilization over nonoperative or delayed treatment. Patients after
      nonoperative and delayed treatment experienced more instability/pathological
      laxity and inability to return to previous activity levels than did patients
      treated with early surgical stabilization.

PMID- 24305649
TI  - Clinical, radiological, and morphological evaluations of posterior horn tears of
      the lateral meniscus left in situ during anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: Recent studies have shown that lateral menisci have a higher healing
      potential and that they can be treated successfully without symptoms by being
      left in situ during anterior cruciate ligament (ACL) reconstruction. However, few
      studies have reported morphological results. HYPOTHESIS: Stable posterior horn
      tears of the lateral meniscus left in situ during ACL reconstruction could be
      healed spontaneously and would result in not only successful clinical outcomes
      but also morphological restoration. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: Among 367 patients who underwent primary ACL reconstruction
      between 2008 and 2010, 53 patients who had lateral meniscus tears that were left
      in situ were analyzed. These patients were evaluated subjectively and
      radiologically and compared with a matched control group that underwent ACL
      reconstruction without any other structural disorders. Of the 53 patients with
      stable posterior horn tears of the lateral meniscus left in situ, 28 patients
      were assessed by second-look arthroscopic surgery and magnetic resonance imaging
      (MRI). RESULTS: The mean follow-up of the study group and the control group was
      36.47 and 37.26 months, respectively. There were no statistical differences in
      postoperative clinical outcomes between the 2 groups. Clinical results of both
      groups including the Lysholm score, Tegner activity score, and International Knee
      Documentation Committee (IKDC) score significantly improved. In the subgroup
      composed of 28 patients, follow-up MRI showed 25 (89%) and 24 (86%) healed
      menisci in sagittal and coronal views, respectively. Twenty-one (75%) were
      considered to be completely healed, and 5 (18%) were incompletely healed on
      second-look arthroscopic surgery. CONCLUSION: Stable posterior horn tears of the
      lateral meniscus left in situ at the time of ACL reconstruction revealed
      successful clinical outcomes compared with isolated ACL injuries and showed
      considerable healing and functional restoration of tears with repeat MRI and
      second-look arthroscopic surgery. Therefore, leaving stable posterior horn tears
      of the lateral meniscus in situ during ACL reconstruction should be considered.

PMID- 24305652
TI  - Virus-induced gene complementation in tomato.
AB  - Virus-induced gene complementation (VIGC), a plant virus technology based on
      Potato virus X for transient overexpression of endogenous genes complemented
      tomato mutants, resulting in non-ripening fruits to ripen. This efficient "gain
      of-function" approach involves no stable transformation, and reveals a fruit
      specific transcriptional network that may exist among key transcription factors
      in modulating tomato ripening. Thus, VIGC represents a novel and feasible
      strategy for gene functional analysis in plants. 

PMID- 24305654
TI  - Butylated hydroxyanisole blocks the occurrence of tumor associated macrophages in
      tobacco smoke carcinogen-induced lung tumorigenesis.
AB  - Tumor-associated macrophages (TAMs) promote tumorigenesis because of their
      proangiogenic and immune-suppressive functions. Here, we report that butylated
      hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in
      tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of
      butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment
      significantly blocked tumor development, although less effectively when BHA is
      administered after NNK treatment. Strikingly, BHA abolished the occurrence of
      F4/80+ macrophages with similar efficiency no matter whether it was administered
      before or after NNK treatment. Detection of cells from bronchioalveolar lavage
      fluid (BALF) confirmed that BHA markedly inhibited the accumulation of
      macrophages while slightly reducing the number of lymphocytes that were induced
      by NNK. Immunohistological staining showed that BHA specifically abolished the
      occurrence of CD206+ TAMs when it was administered before or after NNK treatment.
      Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA
      blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that
      inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco
      smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a
      therapeutic target for treating smoke-induced lung cancer. 

PMID- 24305653
TI  - Towards the Biological Understanding of CTC: Capture Technologies, Definitions
      and Potential to Create Metastasis.
AB  - Circulating Tumor Cells (CTC) are rare cells originated from tumors that travel
      into the blood stream, extravasate to different organs of which only a small
      fraction will develop into metastasis. The presence of CTC enumerated with the
      CellSearch system is associated with a relative short survival and their
      continued presence after the first cycles of therapy indicates a futile therapy
      in patients with metastatic carcinomas. Detailed characterization of CTC holds
      the promise to enable the choice of the optimal therapy for the individual
      patients during the course of the disease. The phenotype, physical and biological
      properties are however not well understood making it difficult to assess the
      merit of recent technological advancements to improve upon the capture of CTC or
      to evaluate their metastatic potential. Here we will discuss the recent advances
      in the classification of CTC captured by the CellSearch system, the implications
      of their features and numbers. Latest capture platforms are reviewed and placed
      in the light of technology improvements needed to detect CTC. Physical
      properties, phenotype, viability and proliferative potential and means to assess
      their proliferation and metastatic capacity will be summarized and placed in the
      context of the latest CTC capture platforms. 

PMID- 24305657
TI  - Graphene nanoribbons hybridized carbon nanofibers: remarkably enhanced
      graphitization and conductivity, and excellent performance as support material
      for fuel cell catalysts.
AB  - High electronic conductivity of the support material and uniform distribution of
      the catalyst nanoparticles (NPs) are extremely desirable for electrocatalysts. In
      this paper, we present our recent progress on electrocatalysts for fuel cells
      with simultaneously improved conductivity of the supporting carbon nanofibers
      (CNFs) and distribution of platinum (Pt) NPs through facile incorporation of
      graphene nanoribbons (GNRs). Briefly, GNRs were obtained by the cutting and
      unzipping of multiwalled carbon nanotubes (MWCNTs) and subsequent thermal
      reduction and were first used as novel nanofillers in CNFs towards high
      performance support material for electrocatalysis. Through electrospinning and
      carbonization processes, GNR embedded carbon nanofibers (G-CNFs) with greatly
      enhanced graphitization and electronic conductivity were synthesized. Chemical
      deposition of Pt NPs onto G-CNFs generated a new Pt-G-CNF hybrid catalyst, with
      homogeneously distributed Pt NPs of ~3 nm. Compared to Pt-CNF (Pt on pristine
      CNFs) and Pt-M-CNF (Pt on MWCNT embedded CNFs), Pt-G-CNF hybrids exhibit
      significantly improved electrochemically active surface area (ECSA), better CO
      tolerance for electro-oxidation of methanol and higher electrochemical stability,
      testifying G-CNFs are promising support materials for high performance
      electrocatalysts for fuel cells. 

PMID- 24305655
TI  - Long Non-Coding RNAs Embedded in the Rb and p53 Pathways.
AB  - In recent years, long non-coding RNAs (lncRNAs) have gained significant attention
      as a novel class of gene regulators. Although a small number of lncRNAs have been
      shown to regulate gene expression through diverse mechanisms including
      transcriptional regulation, mRNA splicing and translation, the physiological
      function and mechanism of action of the vast majority are not known. Profiling
      studies in cell lines and tumor samples have suggested a potential role of
      lncRNAs in cancer. Indeed, distinct lncRNAs have been shown to be embedded in the
      p53 and Rb networks, two of the major tumor suppressor pathways that control cell
      cycle progression and survival. Given the fact that inactivation of Rb and p53 is
      a hallmark of human cancer, in this review we discuss recent evidence on the
      function of lncRNAs in the Rb and p53 signaling pathways. 

PMID- 24305656
TI  - Circulating tumor cells in prostate cancer.
AB  - Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of
      an individual patient's tumor. In prostate cancer, CTC enumeration has been
      extensively studied and validated as a prognostic tool and has received FDA
      clearance for use in monitoring advanced disease. More recently, CTC analysis has
      been shifting from enumeration to more sophisticated molecular characterization
      of captured cells, which serve as a "liquid biopsy" of the tumor, reflecting
      molecular changes in an individual's malignancy over time. Here we will review
      the main CTC studies in advanced and localized prostate cancer, highlighting the
      important gains as well as the challenges posed by various approaches, and their
      implications for advancing prostate cancer management. 

PMID- 24305658
TI  - Evaluation of a Passive Nature Viewing Program Set to Music.
AB  - BACKGROUND: Research has revealed that passive nature viewing (viewing nature
      scenes without actually being in nature) has many health benefits but little is
      known about the best method of offering this complementary modality. AIMS: The
      purpose of this pilot program was to evaluate the impact of a passive nature
      viewing program set to music on stress reduction in adults living in the
      community. DESCRIPTION AND EVALUATION: A pre- and postsurvey design along with
      weekly recordings of stress and relaxation levels were used to evaluate the
      effect of this passive nature viewing program on stress reduction. Participants
      watched one of three preselected nature scenes for 5 minutes a day over 1 month
      and rated their stress and relaxation levels weekly on a 100-mm Visual Analogue
      Scale before and after viewing the nature DVD. Quantitative analysis were not
      performed because of the less number of subjects (n = 10) completing the study.
      Qualitative analysis found five key categories that have an impact on program
      use: (a) technology, (b) personal preferences, (c) time, (d) immersion, and (e)
      use of the program. CONCLUSIONS AND IMPLICATIONS: Holistic nurses may consider
      integrating patient preferences and immersion strategies in the design of future
      passive nature viewing programs to reduce attrition and improve success.

PMID- 24305659
TI  - Humor in the "Twilight Zone": My Work as a Medical Clown With Patients With
      Dementia.
AB  - Medical clowning has been primarily identified with working with children in
      pediatrics wards in hospitals. Over the past decade, more and more medical clowns
      have been working with adults and with patients with dementia as part of holistic
      care. Along with traditional medical care by hospital staff, the medical clown
      treats the patient's emotional side. Furthermore, medical clowning has unique
      advantages in working with patients with dementia. Several studies have shown
      that humor assists in improving the quality of life of patients with dementia.
      The clown, as the ultimate comic figure, creates interactions with patients based
      on humor, which empowers, calms, and strengthens the patient while reinforcing
      the patient's connection with the surroundings. Medical clowning is an
      interdisciplinary therapeutic art, and the medical clown has a "kit" of multiple
      skills (including humor, drama, music, and dance), all of which have a
      beneficial, therapeutic impact on patients. The current article presents and
      analyzes case studies from my work as a medical clown with patients with
      dementia. 

PMID- 24305660
TI  - Topical Ginger Treatment With a Compress or Patch for Osteoarthritis Symptoms.
AB  - AIM: This article is a report of a study evaluating changes in health status
      before and after topical ginger treatment for adults with moderate to severe
      osteoarthritis. METHOD: In 2011, 20 adults with chronic osteoarthritis were
      randomly assigned to one of two groups for 7 consecutive days of topical ginger
      treatment by trained nurses: Group 1 received a manually prepared ginger compress
      and Group 2 a standardized ginger patch. Participants had the option to continue
      self-treatment using the ginger patch for a further 24 weeks. A brief arthritis
      health questionnaire was completed weekly for 3 weeks and 4 weekly for 24 weeks.
      RESULTS: The mean scores for Group 1 and Group 2 show a notable decline following
      1-week topical ginger treatment; scores in pain, fatigue, global effect, and
      functional status reduced by 48%, 49%, 40%, and 31%, respectively, whereas health
      satisfaction improved from 80% dissatisfied to 70% satisfied. Scores for all
      participants in all five domains progressively reduced over the following 24
      weeks of self-treatment. CONCLUSION: Topical ginger treatment has the potential
      to relieve symptoms, improve the overall health, and increase independence of
      people with chronic osteoarthritis.

PMID- 24305661
TI  - A controversial proposal: no more antibiotics for acne!
AB  - Administration of antibiotics, often for prolonged periods, has become the de
      facto standard of care for acne (and rosacea). However, the world is now facing a
      health crisis relating to widespread antibiotic resistance. The authors provide
      current evidence to suggest that dermatologists should consider a radical
      departure from standard operating procedure by severely curtailing, if not
      outright discontinuing, the routine and regular use of antibiotics for acne. 

PMID- 24305662
TI  - An overview of parabens and allergic contact dermatitis.
AB  - Esters of p-hydroxybenzoic acid (parabens) are the most widely used preservatives
      in cosmetic, pharmaceutical, and industrial products. However, since the 1960s,
      controversy has surrounded its use and safety as a potential cause of allergic
      contact dermatitis. Despite the cloud of suspicion that has hovered over parabens
      ever since, these ubiquitous compounds have withstood four decades of extensive
      skin testing conducted by a variety of organizations, both North American and
      European, and now, it seems parabens have shown to be one of the least
      sensitizing preservatives in commercial use. Of the very limited reports of
      paraben-induced allergic contact dermatitis, these cases are often attributable
      to the application of parabens on damaged skin. 

PMID- 24305663
TI  - A method for simultaneously delineating multiple targets in 3D-FISH using limited
      channels, lasers, and fluorochromes.
AB  - Many studies have suggested a link between the spatial organization of genomes
      and fundamental biological processes such as genome reprogramming, gene
      expression, and differentiation. Multicolor fluorescence in situ hybridization on
      three-dimensionally preserved nuclei (3D-FISH), in combination with confocal
      microscopy, has become an effective technique for analyzing 3D genome structure
      and spatial patterns of defined nucleus targets including entire chromosome
      territories and single gene loci. This technique usually requires the
      simultaneous visualization of numerous targets labeled with different colored
      fluorochromes. Thus, the number of channels and lasers must be sufficient for the
      commonly used labeling scheme of 3D-FISH, "one probe-one target". However, these
      channels and lasers are usually restricted by a given microscope system. This
      paper presents a method for simultaneously delineating multiple targets in 3D
      FISH using limited channels, lasers, and fluorochromes. In contrast to other
      labeling schemes, this method is convenient and simple for multicolor 3D-FISH
      studies, which may result in widespread adoption of the technique. Lastly, as an
      application of the method, the nucleus locations of chromosome territory 18/21
      and centromere 18/21/13 in normal human lymphocytes were analyzed, which might
      present evidence of a radial higher order chromatin arrangement. 

PMID- 24305664
TI  - Sister chromatid exchanges in barley.
AB  - A mean frequency of 20.6 sister chromatid exchanges (SCEs) per cell has been
      observed in a reconstructed karyotype of Hordeum vulgare by application of the
      FPG technique after unifilar incorporation of BrdU into chromosomes. The
      involvement in SCEs of the 48 segments into which the chromosome set had been
      subdivided was, with a single deviation, length proportional and independent of
      the segment's heterochromatin content. Asymmetric bands, indicative of an uneven
      distribution of adenine and thymidine between the DNA strands in adenine (A)
      thymidine (T) rich chromosome regions, could not be detected after incubation of
      the cells in BrdU for one cycle of DNA replication. 

PMID- 24305665
TI  - An experimental test of the efficiency of family selection in chickens.
AB  - Responses to single trait selection on individual phenotype and sire-family mean
      phenotype for survivor's egg weight and rate of lay were measured for a single
      generation in 13 replicates. Each replicate-selection criterion-trait subclass
      consisted of eight sire families or 72 females measured and was reproduced from
      the best 25% of the families or individuals. The realized heritability of egg
      weight was 0.39 and that of rate of lay was 0.31, both of which were
      significantly greater than zero but not significantly different from the
      predicted values based on halfsib correlations in the base population.The
      standardized response to sire-family selection was less than the response to
      individual selection for both traits and the difference was significant for rate
      of lay (0.10; 0.31) but not for egg weight (0.22; 0.39). The predicted responses
      to sire-family selection were less than those for individual selection for both
      traits, and the observed responses to sire-family selection were not
      significantly different from the predicted values for either trait.These
      experimental results do not disagree with the theoretical expectations of the
      relative efficiencies of individual and sire-family selection. 

PMID- 24305666
TI  - The occurrence and frequency of 2n pollen in three diploid solanums from
      Northwest Argentina.
AB  - A group of wild, tuber-bearing species from Northwest Argentina, belonging to the
      series Tuberosa, Solarium spegazzini Bitt. (spg, 2n=2x=24), S. gourlayi Hawkes
      (grl, 2n=2x=24 and 2n=4x=48) and S. oplocense Hawkes (opl, 2n=6x=72), and
      Cuneolata, S. infundibuliforme Phil (ifd, 2n=2x=24), is being used to investigate
      the mode of origin of polyploids in the genus Solanum. 2n gametes have been
      detected in the diploid species ifd and spg and in a diploid race of grl, using
      cytological and breeding approaches. Twenty-two introductions of spg, 8 of grl
      and 26 of ifd have been tested for 2n pollen; 59%, 63% and 54% of them,
      respectively, had at least one 2n pollen producing plant. These introductions
      comprised 238, 76 and 235 plant respectively, of which 20, 16, and 32 plant
      produced 5% or more 2n pollen. The mechanism of 2n pollen formation was
      determined in several plant of 2x spg, 2x grl and 2x ifd. All of them were found
      to form diplandroids via parallel spindles. This mechanism, which gives meiotic
      products genetically equivalent to first division restitution gametes, is under
      control of the Mendelian recessive ps. The results suggest that the allele ps is
      widely distributed in natural populations of the three diploids, and that its
      frequency is very high. These species are seen as valuable material for
      population genetic studies, and for the eventual incorporation into a breeding
      scheme involving sexual polyploidization via 2n gametes. 

PMID- 24305667
TI  - Rye chromosome translocations in hexaploid wheat: a re-evaluation of the loss of
      heterochromatin from rye chromosomes.
AB  - Using in situ hybridization techniques, we have been able to identify the
      translocated chromosomes resulting from whole arm interchanges between
      homoeologous chromosomes of wheat and rye. This was possible because radioactive
      probes are available which recognize specific sites of highly repeated sequence
      DNA in either rye or wheat chromosomes. The translocated chromosomes analysed in
      detail were found in plants from a breeding programme designed to substitute
      chromosome 2R of rye into commercial wheat cultivars. The distribution of rye
      highly repeated DNA sequences showed modified chromosomes in which (a) most of
      the telomeric heterochromatin of the short arm and (b) all of the telomeric
      heterochromatin of the long arm, had disappeared. Subsequent analyses of these
      chromosomes assaying for wheat highly repeated DNA sequences showed that in type
      (a), the entire short arm of 2R had been replaced by the short arm of wheat
      chromosome 2B and in (b), the long arm of 2R had been replaced by the long arm of
      2B. The use of these probes has also allowed us to show that rye heterochromatin
      has little effect on the pairing of the translocated wheat arm to its wheat
      homologue during meiosis. We have also characterized the chromosomes resulting
      from a 1B-1R translocation event.From these results, we suggest that the observed
      loss of telomeric heterochromatin from rye chromosomes in wheat is commonly due
      to wheat-rye chromosome translocations. 

PMID- 24305668
TI  - Heterosis for chiasma frequency and quantitative traits in common beans
      (Phaseolus vulgaris L.).
AB  - Ten genotypes, including inbreds, hybrids, and advanced populations, were
      examined in order to elucidate the relationship between position and frequency
      distribution of chiasmata and quantitative traits, including yield heterosis in
      common beans. The hybrid and advanced population groups were determined to
      possess 83% and 54% increased chiasma frequency, respectively in contrast to
      inbred lines. The increase in chiasma frequency of these populations was further
      manifested in a high number of interstitial chiasmata. The regular and superior
      chromosome behaviour of the hybrids was found to be positively associated with
      quantitative measures on bean yield, harvest index and bean yield efficiency. The
      results were discussed from the point of view that: a) increased interstitial
      chiasmata may provide an effective mechanism for maintaining genetic diversity
      and heterosis in hybrid populations; and b) heterosis for chiasma frequency and
      quantitative traits may be due to dispersed genes on the chromosomes having
      combined intra-and interallelic interactions. The data provide evidence for the
      existence of positive associations between interstitially localized chiasmata
      with its recombination potential and regular chromosome behaviour to bean yield
      heterosis. The role of enhanced interstitial chiasmata to promote higher levels
      of genetic variation and heterozygous advantage is discussed. 

PMID- 24305669
TI  - Associations between isozyme phenotypes and environment in the slender wild oat
      (Avena barbata) in Israel.
AB  - Collections from 31 populations of A. barbata from diverse habitats in Israel
      were assayed electrophoretically for seven enzyme systems. Phenotype frequencies
      were scored in nine enzyme zones, probably representing 27 loci, to determine
      isozyme variability within and among populations. Many different isozyme
      phenotypes were found in all of the populations; also the array of isozyme
      phenotypes found in each population differed distinctly from that found in each
      other population. Overlays of phenotypic frequencies on map locations showed that
      isozyme variability is distributed in mosaic patterns not related to geographical
      distance. Principal-component and multiple-regression analyses revealed that
      temperature and moisture-related variables are significantly correlated with
      particular isozyme phenotypes. Further, the mosaic patterns of isozyme variation
      were found to correspond closely to mosaic patterns of the habitat. This
      structuring of the genetic variability into multilocus combinations was
      attributed to the combined effects of directional and diversifying selection.
      Comparisons of patterns and extent of genetic variation in Israel and California
      led to the conclusion that the evolution of 'ecotypes,' each adapted to a
      specific habitat and marked by a particular set of enzyme alleles, has proceeded
      further in Israel, where A. barbata is endemic, than in California, where it is a
      recent introduction. 

PMID- 24305670
TI  - Artificial selection for 18-day pupa weight and opposing simulated naturel
      selection in Tribolium castaneum.
AB  - The effect of simulated opposing natural selection on the response to mass
      selection for 18-day pupa weight of Tribolium castaneum was studied for 10
      generations of selection. Natural selection was simulated in replicated treatment
      lines by imposing a negative relationship between mid-parent genetic value for
      pupa weight and fertility. Responses to selection and realized heritabilities
      were smaller (P < 0.05 and P < 0.10, respectively) for the treatment lines than
      for control lines under selection for pupa weight only. One treatment, line E3G1,
      reached an intermediate selection plateau by generation 10, and responded
      linearly to 4 generations of artificial selection after natural selection had
      been discontinued. Possible explanations for the different behaviors of the
      replicate lines E3G1 and E3G2 were also discussed. 

PMID- 24305671
TI  - The conflict between natural and artificial selection in finite populations.
AB  - A single locus model of the interaction between natural selection and artificial
      selection for a quantitative character in a finite population, assuming
      heterozygote superiority in natural fitness but additive action on the character,
      has been studied using transition probability matrices.If natural selection is
      strong enough to create a selection plateau in which genetic variance declines
      relatively slowly, then the total response to artificial selection prior to the
      plateau will be much less than that expected in the absence of natural selection,
      and the half-life of response will be shorter. Such a plateau is likely to have a
      large proportion, if not all, of the original genetic variance still present. In
      selection programmes using laboratory animals, it seems likely that the
      homozygote favoured by artificial selection must be very unfit before such a
      plateau will occur. A significant decrease in population fitness as a result of
      artificial selection does not necessarily imply that the metric character is an
      important adaptive character.These implications of this model of natural
      selection are very similar to those derived by James (1962) for the optimum model
      of natural selection. In fact, there seems to be no aspect of the observable
      response to artificial selection that would enable anyone to distinguish between
      these two models of natural selection. 

PMID- 24305672
TI  - Aneuploid analysis of low molecular weight gliadins from wheat.
AB  - The chromosomal location of genes affecting five components from the low
      molecular weight gliadin (LMWG) fraction from wheat endosperm has been
      investigated by aneuploid analysis. Genes controlling these proteins were
      assigned to chromosomes 4B, 7A and 7D. Chromosomes from homoeologous groups 1, 2
      and 6, where genes controlling classical gliadins are located, are not involved
      in the control of LMWG. 

PMID- 24305673
TI  - Gene-ecological investigations in Pisum mutants : Part 2: comparative performance
      in Germany and North India.
AB  - Six mutants and nine recombinants of Pisum sativum were grown along with the
      mother variety at Kurukshetra, North India. The findings obtained were compared
      with those obtained for the same material grown at Bonn, Germany. The following
      observations were made.Stem length and degree of branching are influenced
      differentially in the various genotypes tested in India as a consequence of a
      specific reaction of the genes to the climatic conditions. A gene for weak stem
      fasciation and gene efr for earliness in a specific gene combination are unable
      to express their action in North India whereas they are fully active in Germany.
      Furthermore, in Kurukshetra early flowering of some recombinants does not result
      in early ripening because their seeds require about double the time for full
      ripening than those of the mother variety.At Kurukshetra, recombinant R 674A
      proved to be highly heat susceptible. All the plants died in early stages of
      ontogenetic development. Four other genotypes died due to heat before completing
      seed ripening. One mutant and three recombinants were found to be more tolerant
      to powdery mildew attack than the mother variety and Indian local lines. The seed
      production of eight genotypes in relation to that of the initial line was
      essentially better in North India than in Germany. They are obviously better
      adapted to the semi-arid conditions. Some of them appear to be useful for pea
      breeding in India. In contrast, a fasciated mutant, high yielding in Germany, is
      not able to express this potentiality at Kurukshetra. At Udaipur (Rajasthan,
      Western India), this mutant is unable to flower. Another four genotypes, tested
      at both Indian locations, exhibited an essentially poorer seed production at
      Udaipur than at Kurukshetra due to some ecological factors.The findings indicate
      a specific response of some of the genotypes tested to the specific ecological
      conditions of the three locations, their response differing from that of the
      mother variety demonstrating thereby a different adaptational optimum. 

PMID- 24305674
TI  - Cultivar x environment interactions in sorghum, Sorghum bicolor (L.) moench.
AB  - The most significant and important interactions in 2, and 3-year sorghum zonal
      trials were location x year, cultivar x location and cultivar x location x year.
      Cultivar x year interaction was significant in one out of four ecologic zones
      used in the trials. The variance components were relatively small with the second
      order interaction variance component larger than the first order types involving
      cultivars. Environmental variance was the largest in all four zones.Computations
      on theoretical standard error of cultivar means suggest that six replications,
      eight locations and four years is an ideal testing procedure in the Northern
      Guinea Savanna, while in the Sudan Savanna, the combination is better with four
      replications, eight locations and three years. The true value or performance of a
      variety is most effectively obtained by increasing the number of years, while
      increasing number of replications is the least effective. 

PMID- 24305676
TI  - Isolated plant protoplasts in genetics and plant breeding : Bad Honnef (Federal
      Republic of Germany), February 12-14, 1979.

PMID- 24305675
TI  - Genetics of desynaptic mutants in pearl millet.
AB  - Two desynaptic mutants, one of spontaneous origin and the other induced through
      colchicine treatment, were obtained in pearl millet. The desynpatic character was
      a monogenically controlled recessive one. Tests for allelism have indicated that
      the desynaptic genes of the two sources were allelic. Both complete and medium
      strong desynaptic plants followed a monogenic pattern of inheritance and were
      found to be allelic. Medium-strong desynpatic plants on selfing produced both
      complete and medium-strong desynaptics in approximately equal numbers. It is
      suggested that the differential expression of the desynaptic character might be
      due to the presence of modifying genes. 

PMID- 24305677
TI  - Combining ability analysis of beta-Carotene, total carotenoids and other grain
      characteristics in pearl millet.
AB  - Combining ability studies with respect to grain quality characteristics viz.,
      beta-Carotene, total carotenoids, protein content, 250-grain weight, grain
      hardness and grain yield were carried out from a 13x13 diallel cross set in pearl
      millet [Pennisetum typhoides (Burm S&H)].The parents versus hybrids comparison
      indicated significant heterosis for all the traits under study. In general the
      hybrids having higher grain yield had bold hard grains with more carotene but low
      protein content, although a few hybrids combined high yield with an average
      protein percentage. The relative proportions of the general and specific
      combining ability variances indicated predominance of non-additive genetic
      variance with respect to all the traits. The per se performance of parents
      provided a fairly good indication of their combining ability in most cases.
      Parents possessing desirable grain quality characteristics were identified.
      Breeding implications are discussed. 

PMID- 24305678
TI  - First-principles study of hydrogen configurations at the core of a high-angle
      grain boundary in cubic yttria-stabilized zirconia.
AB  - Hydrogen is a common impurity in oxides and has been studied extensively by first
      principles electronic structure methods. From the calculated charge-transition
      levels and their position with respect to the conduction-band edge, definitive
      conclusions can be drawn concerning the electrical activity of hydrogen either as
      an isolated defect or as part of a defect complex with intrinsic defects of the
      host lattice. For those oxides such as yttria-stabilized zirconia, which in many
      cases are used in polycrystalline or nanocrystalline forms, the interaction of
      hydrogen with grain boundaries needs to be better understood. Using both density
      functional theory in the generalized-gradient approximation and a hybrid
      functional approach, the present study reports on the types of isolated hydrogen
      configuration that can be stabilized at the core of the Sigma5(310) tilt grain
      boundary, an interface whose atomistic structure has been determined in good
      detail by Z-contrast transmission electron microscopy. Initially, the present
      calculations elucidated the major relaxation modes that lead to low-energy
      structures for this boundary. Hydrogen exhibited dual behavior by binding to
      oxygen ions in bond-type OH(-) configurations in its positively charged state,
      H(+), whereas the negative H(-) species occupied preferably interstitial
      positions in the available empty space of the grain-boundary core regions. The
      neutral paramagnetic state, H(0), detected recently in muonium-based
      spectroscopic studies, was found to be stable in two different configurations: a
      deep-donor bond-type and a higher-energy quasiatomic interstitial. These
      configurations are characterized in terms of the trapping character of their
      excess electron, the spatial localization of the spin density and the resulting
      hyperfine parameters. 

PMID- 24305679
TI  - Melanin-concentrating hormone receptor 1 polymorphisms are associated with
      components of energy balance in the Complex Diseases in the Newfoundland
      Population: Environment and Genetics (CODING) study.
AB  - BACKGROUND: The melanin-concentrating hormone receptor 1 (MCHR1) is a G protein
      coupled receptor that regulates energy balance and body composition in animal
      models. Inconsistent effects of MCHR1 polymorphisms on energy homeostasis in
      humans may partly be attributable to environmental factors. OBJECTIVES: We
      examined the effect of 4 single nucleotide polymorphisms (rs133073, rs133074,
      rs9611386, and rs882111) in the MCHR1 gene on body composition as well as energy
      related lifestyle factors (diet and physical activity). We also examined the
      effect of gene-lifestyle interactions on body composition. DESIGN: A total of
      1153 participants (248 men and 905 women) from the cross-sectional Complex
      Diseases in the Newfoundland Population: Environment and Genetics (CODING) study
      were genotyped by using probe-based chemistry validated assays. Diet and physical
      activity were estimated by using validated frequency questionnaires, and body
      composition was assessed by using dual-energy X-ray absorptiometry. RESULTS:
      Three polymorphisms (rs9611386, rs882111, and rs133073) were associated with
      differences in body-composition measurements (all P < 0.05). There was an
      interaction between rs9611386 and carbohydrate intake on total mass and waist
      circumference (both P <= 0.01). There was also an interaction between rs9611386
      and body mass index categories (normal weight, overweight, and obese) on energy
      intakes (P = 0.02). A similar interaction was shown with rs882111 (P = 0.02).
      Interactions were also observed between each of these polymorphisms (rs9611386,
      rs882111, and rs133073) and physical activity score on body-composition
      measurements (all P < 0.05). CONCLUSION: These findings suggest that
      polymorphisms in the MCHR1 gene are associated with differences in body
      composition and interact with physiologic and energy-related lifestyle factors.

PMID- 24305680
TI  - Dietary patterns associated with magnetic resonance imaging-determined liver fat
      content in a general population study.
AB  - BACKGROUND: The association between diet and fatty liver disease (FLD) has
      predominantly been analyzed for single nutrients or foods, and findings have been
      inconsistent. OBJECTIVE: We aimed to compare associations of hypothesis-driven
      and exploratory dietary pattern scores with liver fat content. DESIGN: Liver fat
      was measured by using magnetic resonance imaging as liver signal intensity (LSI)
      in a population-based, cross-sectional study that included 354 individuals. We
      applied partial least-squares regression to derive an exploratory dietary pattern
      score that explained variation in both the intake of 38 food groups, which were
      assessed by using a food-frequency questionnaire, and LSI. The hypothesis-driven
      score was calculated on the basis of published studies. Multivariable linear or
      logistic regression was used to investigate associations between dietary pattern
      scores and LSI or FLD. RESULTS: A higher percentage of LSI variation was
      explained by the exploratory (12.6%) compared with the hypothesis-driven (2.2%)
      dietary pattern. Of the 13 most important food groups of the exploratory dietary
      pattern, intakes of green and black tea, soups, and beer were also individually
      associated with LSI values. A 1-unit increase in the exploratory dietary pattern
      score was positively associated with FLD (OR: 1.56; 95% CI: 1.29, 1.88).
      Furthermore, a 1-unit increase in the hypothesis-driven dietary pattern score,
      which consisted of alcohol, soft drinks, meat, coffee, and tea, was positively
      associated with FLD (OR: 1.25; 95% CI: 1.10, 1.43). CONCLUSION: We defined a
      hypothesis-driven dietary pattern and derived an exploratory dietary pattern,
      both of which included alcohol, meat (poultry), and tea, associated with liver
      fat content independent from confounders, which should be explored in prospective
      studies.

PMID- 24305681
TI  - The effects of high-intensity exercise on neural responses to images of food.
AB  - BACKGROUND: Acute bouts of high-intensity exercise modulate peripheral appetite
      regulating hormones to transiently suppress hunger. However, the effects of
      physical activity on central appetite regulation have yet to be fully
      investigated. OBJECTIVE: We used functional magnetic resonance imaging (fMRI) to
      compare neural responses to visual food stimuli after intense exercise and rest.
      DESIGN: Fifteen lean healthy men [mean +/- SD age: 22.5 +/- 3.1 y; mean +/- SD
      body mass index (in kg/m(2)): 24.2 +/- 2.4] completed two 60-min trials-exercise
      (EX; running at ~70% maximum aerobic capacity) and a resting control trial (REST)
      in a counterbalanced order. After each trial, an fMRI assessment was completed in
      which images of high- and low-calorie foods were viewed. RESULTS: EX
      significantly suppressed subjective appetite responses while increasing thirst
      and core-body temperature. Furthermore, EX significantly suppressed ghrelin
      concentrations and significantly enhanced peptide YY release. Neural responses to
      images of high-calorie foods significantly increased dorsolateral prefrontal
      cortex activation and suppressed orbitofrontal cortex (OFC) and hippocampus
      activation after EX compared with REST. After EX, low-calorie food images
      increased insula and putamen activation and reduced OFC activation compared with
      REST. Furthermore, left pallidum activity was significantly elevated after EX
      when low-calorie images were viewed and was suppressed when high-calorie images
      were viewed, and these responses correlated significantly with thirst.
      CONCLUSIONS: Exercise increases neural responses in reward-related regions of the
      brain in response to images of low-calorie foods and suppresses activation during
      the viewing of high-calorie foods. These central responses are associated with
      exercise-induced changes in peripheral signals related to appetite-regulation and
      hydration status. This trial was registered at www.clinicaltrials.gov as
      NCT01926431.

PMID- 24305682
TI  - 2-Diazo-1-(4-hydroxyphenyl)ethanone: a versatile photochemical and synthetic
      reagent.
AB  - alpha-Diazo arylketones are well-known substrates for Wolff rearrangement to
      phenylacetic acids through a ketene intermediate by either thermal or
      photochemical activation. Likewise, alpha-substituted p-hydroxyphenacyl (pHP)
      esters are substrates for photo-Favorskii rearrangements to phenylacetic acids by
      a different pathway that purportedly involves a cyclopropanone intermediate. In
      this paper, we show that the photolysis of a series of alpha-diazo-p
      hydroxyacetophenones and p-hydroxyphenacyl (pHP) alpha-esters both generate the
      identical rearranged phenylacetates as major products. Since alpha-diazo-p
      hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for
      either Wolff or Favorskii rearrangement, we were prompted to probe this
      intriguing mechanistic dichotomy under conditions favorable to the photo
      Favorskii rearrangement, i.e., photolysis in hydroxylic media. An investigation
      of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using
      time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of
      a ketene intermediate that is subsequently trapped by solvent or nucleophiles.
      The photoreaction of 1a is quenched by oxygen and sensitized by triplet
      sensitizers and the quantum yields for 1a-c range from 0.19 to a robust 0.25. The
      lifetime of the triplet, determined by Stern-Volmer quenching, is 31 ns with a
      rate for appearance of 4a of k = 7.1 * 10(6) s(-1) in aq. acetonitrile (1 : 1 v :
      v). These studies establish that the primary rearrangement pathway for 1a
      involves ketene formation in accordance with the photo-Wolff rearrangement.
      Furthermore we have also demonstrated the synthetic utility of 1a as an
      esterification and etherification reagent with a variety of substituted alpha
      diazo-p-hydroxyacetophenones, using them as synthons for efficiently coupling it
      to acids and phenols to produce pHP protect substrates.

PMID- 24305683
TI  - Mechanisms of molecular transport through the urea channel of Helicobacter
      pylori.
AB  - Helicobacter pylori survival in acidic environments relies on cytoplasmic
      hydrolysis of gastric urea into ammonia and carbon dioxide, which buffer the
      pathogen's periplasm. Urea uptake is greatly enhanced and regulated by HpUreI, a
      proton-gated inner membrane channel protein essential for gastric survival of H.
      pylori. The crystal structure of HpUreI describes a static snapshot of the
      channel with two constriction sites near the center of the bilayer that are too
      narrow to allow passage of urea or even water. Here we describe the urea
      transport mechanism at atomic resolution, revealed by unrestrained microsecond
      equilibrium molecular dynamics simulations of the hexameric channel assembly. Two
      consecutive constrictions open to allow conduction of urea, which is guided
      through the channel by interplay between conserved residues that determine proton
      rejection and solute selectivity. Remarkably, HpUreI conducts water at rates
      equivalent to aquaporins, which might be essential for efficient transport of
      urea at small concentration gradients. 

PMID- 24305684
TI  - Possible association of cutaneous Rosai-Dorfman disease and chronic Crohn
      disease: a case series report.
AB  - IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman
      disease limited to the skin, has a wide range of clinical presentations. Rosai
      Dorfman disease is believed to result from an aberrant response to antigens,
      caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is
      also implicated in the pathogenesis of Crohn disease, linking these otherwise
      unrelated entities. To our knowledge, the coexistence of these disorders has been
      described in only 2 cases, 1 of them confined to the skin and soft tissue.
      OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the
      context of long-standing Crohn disease. Statistical estimates suggested that the
      association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND
      RELEVANCE Our case series provides the clinical correlate to the pathogenetic
      parallels between CRDD and Crohn disease. Crohn disease is frequently complicated
      by various skin manifestations, which may be mimicked by CRDD. Therefore, it may
      be prudent for clinicians to include CRDD in the list of differential diagnoses
      when examining skin lesions in patients with Crohn disease.

PMID- 24305685
TI  - Quality markers addressing preanalytical variations of blood and plasma
      processing identified by broad and targeted metabolite profiling.
AB  - BACKGROUND: Metabolomics is a valuable tool with applications in almost all life
      science areas. There is an increasing awareness of the essential need for high
      quality biospecimens in studies applying omics technologies and biomarker
      research. Tools to detect effects of both blood and plasma processing are a key
      for assuring reproducible and credible results. We report on the response of the
      human plasma metabolome to common preanalytical variations in a comprehensive
      metabolomics analysis to reveal such high-quality markers. METHODS: Human EDTA
      blood was subjected to preanalytical variations while being processed to plasma:
      microclotting, prolonged processing times at different temperatures, hemolysis,
      and contamination with buffy layer. In a second experiment, EDTA plasma was
      incubated at different temperatures for up to 16 h. Samples were subjected to GC
      MS and liquid chromatography-tandem mass spectrometry-based metabolite profiling
      (MxPTM Broad Profiling) complemented by targeted methods, i.e., sphingoids (as
      part of MxPTM Lipids), MxPTM Catecholamines, and MxPTM Eicosanoids. RESULTS:
      Short-term storage of blood, hemolysis, and short-term storage of noncooled
      plasma resulted in statistically significant increases of 4% to 19% and decreases
      of 8% to 12% of the metabolites. Microclotting, contamination of plasma with
      buffy layer, and short-term storage of cooled plasma were of less impact on the
      metabolome (0% to 11% of metabolites increased, 0% to 8% decreased). CONCLUSIONS:
      The response of the human plasma metabolome to preanalytical variation demands
      implementation of thorough quality assurance and QC measures to obtain
      reproducible and credible results from metabolomics studies. Metabolites
      identified as sensitive to preanalytics can be used to control for sample
      quality.

PMID- 24305686
TI  - Practice-oriented quality specifications for therapeutic drug monitoring.

PMID- 24305687
TI  - As if biomarker discovery isn't hard enough: the consequences of poorly
      characterized reagents.

PMID- 24305688
TI  - Korovkin-type theorems in weighted Lp-spaces via summation process.
AB  - Korovkin-type theorem which is one of the fundamental methods in approximation
      theory to describe uniform convergence of any sequence of positive linear
      operators is discussed on weighted Lp spaces, 1 <= p < infinity for univariate
      and multivariate functions, respectively. Furthermore, we obtain these types of
      approximation theorems by means of A-summability which is a stronger convergence
      method than ordinary convergence.

PMID- 24305691
TI  - Addressing the nursing workforce shortage: veterans as mental health nurses.

PMID- 24305689
TI  - Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10.
AB  - Glioma is the most frequent primary brain tumor. Recently, the upregulation of
      microRNA (miR)-23a was found to be associated with glioma, but the molecular
      mechanism by which miR-23a promotes glioma growth remains to be unveiled. In the
      present study, we found that miR-23a was significantly upregulated in glioma
      tissues compared to their matched adjacent tissues. miR-23a was also highly
      expressed in glioma cell lines SHG44, U251, and U87 cells. Moreover, we
      identified homeobox D10 (HOXD10) as a novel target for miR-23a. The expression of
      HOXD10 was significantly reduced in glioma tissues and cell lines, and miR-23a
      negatively regulates the protein expression of HOXD10 in U251 and U87 cells. We
      further showed that miRNA-23a promoted U251 and U87 cell invasion, at least
      partially, by directly targeting HOXD10 and further modulating MMP-14. These
      findings suggest that miR-23a may serve as a promising therapeutic target for
      glioma. 

PMID- 24305693
TI  - FDA-approved drugs to treat Schizophrenia.

PMID- 24305696
TI  - Prepatellar and olecranon bursitis: literature review and development of a
      treatment algorithm.
AB  - PURPOSE: Olecranon bursitis and prepatellar bursitis are common entities, with a
      minimum annual incidence of 10/100,000, predominantly affecting male patients (80
      %) aged 40-60 years. Approximately 1/3 of cases are septic (SB) and 2/3 of cases
      are non-septic (NSB), with substantial variations in treatment regimens
      internationally. The aim of the study was the development of a literature review
      based treatment algorithm for prepatellar and olecranon bursitis. METHODS:
      Following a systematic review of Pubmed, the Cochrane Library, textbooks of
      emergency medicine and surgery, and a manual reference search, 52 relevant papers
      were identified. RESULTS: The initial differentiation between SB and NSB was
      based on clinical presentation, bursal aspirate, and blood sampling analysis.
      Physical findings suggesting SB were fever >37.8  degrees C, prebursal
      temperature difference greater 2.2  degrees C, and skin lesions. Relevant
      findings for bursal aspirate were purulent aspirate, fluid-to-serum glucose ratio
      <50 %, white cell count >3,000 cells/MUl, polymorphonuclear cells >50 %, positive
      Gram staining, and positive culture. General treatment measures for SB and NSB
      consist of bursal aspiration, NSAIDs, and PRICE. For patients with confirmed NSB
      and high athletic or occupational demands, intrabursal steroid injection may be
      performed. In the case of SB, antibiotic therapy should be initiated. Surgical
      treatment, i.e., incision, drainage, or bursectomy, should be restricted to
      severe, refractory, or chronic/recurrent cases. CONCLUSIONS: The available
      evidence did not support the central European concept of immediate bursectomy in
      cases of SB. A conservative treatment regimen should be pursued, following bursal
      aspirate-based differentiation between SB and NSB.

PMID- 24305697
TI  - Synthesis of substituted exo-glucals via a modified Julia olefination and
      identification as selective beta-glucosidase inhibitors.
AB  - A series of fluorine and non-fluorine-substituted C-glucosylidenes (exo-glucals)
      has been synthesized via a modified Julia olefination. The deprotected exo
      glucals were prepared in five steps from commercially available d-gluconolactone.
      The evaluation of this original family of compounds against a panel of
      glycosidases showed a highly specific in vitro activity towards mammalian beta
      glucosidase depending on the double bond substituents. 

PMID- 24305698
TI  - Donor-acceptor-donor type organic semiconductor containing quinoidal benzo[1,2
      b:4,5-b']dithiophene for high performance n-channel field-effect transistors.
AB  - A donor-acceptor-donor (D-A-D) type small molecule , with dicyano-substituted
      quinoidal benzo[1,2-b:4,5-b']dithiophene as the acceptor, was designed and
      synthesized. A high electron mobility up to 0.88 cm(2) V(-1) s(-1) was observed
      for based transistors under ambient conditions, suggesting quinoidal benzo[1,2
      b:4,5-b']dithiophene is an excellent acceptor unit in D-A type n-channel organic
      semiconductors. 

PMID- 24305699
TI  - Health impact assessment of exposure to fine particulate matter based on
      satellite and meteorological information.
AB  - Air pollution in China, especially in the Pearl River Delta (PRD) region, has
      drastically increased in recent years. We modelled annual mean ground-level PM2.5
      concentrations based on worldwide satellite information and meteorological data
      from 40 cities outside the PRD. The model of PM2.5 concentration (R = 0.845) was
      best explained by aerosol optical thickness (43.8%). We validated the spatial
      temporal dimensions of the model and estimated that the annual mean PM2.5
      concentration in PRD ranged between 22 and 65 MUg m(-3). Then we used meta
      analysis to obtain the pooled excess risks of mortality in China and assessed the
      health impacts. We found an inverse association between short-term excess risks
      of mortality and annual mean PM2.5 concentrations. Based on the above models and
      analyses, the associated excess deaths for all-cause and cardiopulmonary diseases
      were 3386 and 2639 respectively. The corresponding risk-standardized excess death
      rates were 2006 and 1069 per million people. 

PMID- 24305700
TI  - Activation of group 2 metabotropic glutamate receptors reduces behavioral and
      electrographic correlates of pilocarpine induced status epilepticus.
AB  - Novel treatments for epilepsy are necessary because many epilepsy patients are
      resistant to medication. Metabotropic glutamate receptors (mGluRs), specifically
      mGluR 2 and 3, may serve as antiepileptic drug targets because of their role in
      controlling synaptic release. In this study, we administered a Group 2 mGluR
      agonist, LY379268, one of two mGluR2-specific positive allosteric modulators,
      BINA or CBiPES, or a cocktail of both BINA and LY379268 in a series of
      experiments using the pilocarpine model of SE. In one study, groups received
      treatments 15 min prior to pilocarpine, while in a second study groups received
      treatments after SE had been initiated to determine whether the drugs could
      reduce development and progression of SE. We measured bouts of stage 5 seizures,
      latency to the first seizure, and the maximum Racine score to characterize the
      seizure severity. We analyzed mouse EEG with implanted electrodes using a power
      analysis. We found that pretreatment and posttreatment with LY379268 was
      effective at reducing both behavioral correlates and power in EEG bandwidths
      associated with seizure, while CBiPES was less effective and BINA was
      ineffective. These data generally support continued development of mGluR2
      pharmacology for novel antiepileptic drugs, though further study with additional
      drugs and concentrations will be necessary.

PMID- 24305701
TI  - Significant prevalence of antibodies reacting with simian virus 40 mimotopes in
      sera from patients affected by glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is a rare tumor, which affects 1/100
      000 individuals, but it represents 30% of central nervous system malignancies.
      GBM is a severe tumor responsible for 2% of all cancer-related deaths. Although
      characterized by genotypic and phenotypic heterogeneities, GBM invariably resists
      conventional chemo- and radiotherapies. Several chromosome alterations and gene
      mutations were detected in GBM. Simian virus 40 (SV40), a small DNA tumor virus,
      has been found in GBM specimens by some studies, while other investigations have
      not confirmed the association. METHODS: An indirect enzyme-linked immunosorbent
      assay with 2 synthetic peptides mimicking SV40 antigens of viral capsid proteins
      1-3 was employed to detect specific antibodies against SV40 in serum samples from
      GBM-affected patients, together with controls represented by patients affected by
      breast cancer and normal subjects of the same median age. RESULTS: Our data
      indicate that in serum samples from GBM-affected patients (n = 44), the
      prevalence of antibodies against SV40 viral capsid protein antigens is
      statistically significantly higher (34%, P = .016 and P = .03) than in the
      control groups (15%), represented by healthy subjects (n = 101) and patients
      affected by breast cancer (n = 78), respectively. CONCLUSION: Our data indicate
      that SV40, or a closely related yet undiscovered human polyomavirus, is
      associated with a subset of GBM and circulates in humans. Our study can be
      transferred to the clinical oncology application to discriminate different types
      of heterogeneous GBM, which in turn may address an innovative therapeutic
      approach to this fatal cancer.

PMID- 24305702
TI  - Targeting Wee1 for the treatment of pediatric high-grade gliomas.
AB  - BACKGROUND: We investigated the efficacy of the Wee1 inhibitor MK-1775 in
      combination with radiation for the treatment of pediatric high-grade gliomas
      (HGGs), including diffuse intrinsic pontine gliomas (DIPGs). METHODS: Gene
      expression analysis was performed for 38 primary pediatric gliomas (3 grade I, 10
      grade II, 11 grade III, 14 grade IV) and 8 normal brain samples using the Agilent
      4 * 44 K array. Clonogenic survival assays were carried out in pediatric and
      adult HGG cell lines (n = 6) to assess radiosensitizing effects of MK-1775. DNA
      repair capacity was evaluated by measuring protein levels of gamma-H2AX, a marker
      of double strand DNA breaks. In vivo activity of MK-1775 with radiation was
      assessed in 2 distinct orthotopic engraftment models of pediatric HGG, including
      1 derived from a genetically engineered mouse carrying a BRAF(V600E) mutation,
      and 1 xenograft model in which tumor cells were derived from a patient's DIPG.
      RESULTS: Wee1 is overexpressed in pediatric HGGs, with increasing expression
      positively correlated with malignancy (P = .007 for grade III + IV vs I + II) and
      markedly high expression in DIPG. Combination treatment of MK-1775 and radiation
      reduced clonogenic survival and increased expression of gamma-H2AX to a greater
      extent than achieved by radiation alone. Finally, combined MK-1775 and radiation
      conferred greater survival benefit to mice bearing engrafted, orthotopic HGG and
      DIPG tumors, compared with treatment with radiation alone (BRAF(V600E) model P =
      .0061 and DIPG brainstem model P = .0163). CONCLUSION: Our results highlight MK
      1775 as a promising new therapeutic agent for use in combination with radiation
      for the treatment of pediatric HGGs, including DIPG.

PMID- 24305703
TI  - MiR-328 promotes glioma cell invasion via SFRP1-dependent Wnt-signaling
      activation.
AB  - Background Diffusely infiltrative growth of human astrocytic gliomas is one of
      the major obstacles to successful tumor therapy. Thorough insights into the
      molecules and pathways signaling glioma cell invasion thus appear of major
      relevance for the development of targeted and individualized therapies. By miRNA
      expression profiling of microdissected human tumor biopsy specimens we identified
      miR-328 as one of the main miRNAs upregulated in invading glioma cells in vivo
      and further investigated its role in glioma pathogenesis. Methods We employed
      miRNA mimics and inhibitors to functionally characterize miR-328, 3' untranslated
      region luciferase assays, and T-cell factor/lymphoid enhancer factor reporter
      assays to pinpoint miR-328 targets and signaling pathways, and analyzed miR-328
      expression in a large panel of gliomas. Results First, we corroborated the
      invasion-promoting role of miR-328 in A172 and TP365MG glioma cells. Secreted
      Frizzled-related protein 1 (SFRP1), an inhibitor of Wnt signaling, was then
      pinpointed as a direct miR-328 target. SFRP1 expression is of prognostic
      relevance in gliomas with reduced expression, being associated with significantly
      lower overall patient survival in both the Repository of Molecular Brain
      Neoplasia Data (REMBRANDT) and The Cancer Genome Atlas. Of note, miR-328
      regulated both SFRP1 protein expression levels and Wnt signaling pathway
      activity. Finally, in human glioma tissues miR-328 appeared to account for the
      downregulation of SFRP1 preferentially in lower-grade astrocytic gliomas and was
      inversely related to SFRP1 promoter hypermethylation. Conclusion Taken together,
      we report on a novel molecular miR-328-dependent mechanism that via SFRP1
      inhibition and Wnt activation contributes to the infiltrative glioma phenotype at
      already early stages of glioma progression, with unfavorable prognostic
      implications for the final outcome of the disease. 

PMID- 24305704
TI  - Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of
      hypoxia and vascularity in specific areas of intratumoral microenvironment and is
      predictive of patient outcome.
AB  - BACKGROUND: Measures of tumor vascularity and hypoxia have been correlated with
      glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively
      map tumor blood flow, vascularity, and permeability. In this prospective
      observational cohort pilot study, preoperative imaging was correlated with
      molecular markers of hypoxia, vascularity, proliferation, and progression-free
      and overall patient survival. METHODS: Pharmacokinetic modeling methods were used
      to generate maps of tumor blood flow, extraction fraction, permeability-surface
      area product, transfer constant, washout rate, interstitial volume, blood volume,
      capillary transit time, and capillary heterogeneity from preoperative DCE-MRI
      data in human glioma patients. Tissue was obtained from areas of peritumoral
      edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for
      vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE
      MRI parameter values were correlated with hypoxia-regulated protein expression at
      tissue sample sites. RESULTS: Patient survival correlated with DCE parameters in
      2 cases: capillary heterogeneity in active tumor and interstitial volume in areas
      of peritumoral edema. Statistically significant correlations were observed
      between several DCE parameters and tissue markers. In addition, MIB-1 index was
      predictive of overall survival (P = .044) and correlated with vascular
      endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P = .0071)
      and peritumoral edema (r = 0.4546). Increased microvessel density correlated with
      worse patient outcome (P = .026). CONCLUSIONS: Our findings suggest that DCE-MRI
      may facilitate noninvasive preoperative predictions of areas of tumor with
      increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are
      predictive of patient outcome. This has the potential to allow unprecedented
      prognostic decisions and to guide therapies to specific tumor areas.

PMID- 24305705
TI  - Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6
      glioma.
AB  - BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIONs), due to their
      unique magnetic properties, have the ability to function both as magnetic
      resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs
      conjugated to the heat shock protein Hsp70 that selectively binds to the CD40
      receptor present on glioma cells, could be used for MR contrast enhancement of
      experimental C6 glioma. METHODS: The magnetic properties of the Hsp70-SPIONs were
      measured by NMR relaxometry method. The uptake of nanoparticles was assessed on
      the C6 glioma cells by confocal and electron microscopes. The tumor selectivity
      of Hsp70-SPIONs being intravenously administered was analyzed in the experimental
      model of C6 glioma in the MRI scanner. RESULTS: Hsp70-SPIONs relaxivity
      corresponded to the properties of negative contrast agents with a hypointensive
      change of resonance signal in MR imaging. A significant accumulation of the Hsp70
      SPIONs but not the non-conjugated nanoparticles was observed by confocal
      microscopy within C6 cells. Negative contrast tumor enhancement in the T2
      weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non
      modified SPIONs. Histological analysis of the brain sections confirmed the
      retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal
      brain tissues. CONCLUSION: The study demonstrated that Hsp70-SPION conjugate
      intravenously administered in C6 glioma model accumulated in the tumors and
      enhanced the contrast of their MR images.

PMID- 24305706
TI  - Clinical and prognostic features of adult patients with gangliogliomas.
AB  - BACKGROUND: Gangliogliomas (GGs) represent <1% of primary brain tumors in adults.
      Little is known regarding prognostic features, clinical characteristics, or the
      impact of treatment on patient outcomes. METHODS: Our neuro-oncology longitudinal
      database was screened for patients with GG from 1992 to 2012. Sixty-seven
      patients (age >18 y) were identified. RESULTS: Sixty-two patients presented with
      low-grade GG and 5 with anaplastic GG. The median age at diagnosis was 29 years.
      With a median follow-up of 4.7 years after the initial diagnosis, 23 patients had
      progressive disease. Range of time to progression was 0.2-20 years. Nine patients
      with low-grade GG progressed to a malignant tumor. The median overall survival
      (OS) for all patients was not reached. The 2-, 5-, and 10-year OS for patients
      with low-grade GG were 100%, 88% (95% confidence interval [CI]: 73%, 95%), and
      84% (95% CI: 67%, 93%), respectively. Factors identified by univariate analysis
      that were significantly associated with OS were age, KPS, extent of resection
      (EOR), and grade. Factors on univariate analysis that were significantly
      associated with progression-free survival were grade and EOR. On multicovariate
      Cox regression, lower tumor grade and younger age were significant factors for
      longer OS. EOR is a significant factor for progression-free survival.
      CONCLUSIONS: While GG has excellent prognosis, malignant histologic grade, older
      age, and diagnosis with biopsy could indicate worse prognosis. The late nature
      and high rate of progression emphasize the importance of long-term follow-up. The
      role of chemotherapy and radiation therapy for incompletely resected low-grade GG
      remains unclear.

PMID- 24305707
TI  - Physical functioning in pediatric survivors of childhood posterior fossa brain
      tumors.
AB  - BACKGROUND: Survival rates for children diagnosed with posterior fossa brain
      tumors (PFBTs) have improved significantly over the past several decades, and
      long-term functioning assessments have become priorities. These evaluations have
      occurred frequently in adults but only rarely in children. This study describes a
      cross-sectional assessment of physical functioning in pediatric survivors of
      PFBTs using the Bruininks-Osteretsky Test of Motor Performance, Second Edition
      (BOT-2). METHODS: Primary analyses compared BOT-2 scores to normative data using
      1-sample t tests for each gross motor subscale (Bilateral Coordination, Balance,
      Running Speed/Agility, Strength) and motor-area composite (Body Coordination and
      Strength and Agility). Second, the cohort was stratified by diagnostic or
      treatment variables. Group differences and groups vs norms were evaluated using
      independent 2-sample and 1-sample t tests, respectively. Primary analyses
      compared BOT-2 scores with normative data using 1-sample t tests for each gross
      motor subscale (Bilateral Coordinationcoordination, Balance, Running
      Speed/Agility, Strength) and motor-area composite (Body Coordination and Strength
      and Agility). Second, the cohort was stratified by diagnostic or treatment
      variables. Group differences and groups vs norms were evaluated using independent
      2-sample and 1-sample t tests, respectively. RESULTS: Mean age of 30 participants
      was 11.4 years (range, 4.9y-18.2y), and mean time from diagnosis was 6.1 years
      (range, 1.1y-16.7y). Cerebellar astrocytoma (43.3%) and medulloblastoma (40%)
      were the most common diagnoses. As a group, significantly decreased functioning,
      compared with norms, was observed in Balance (P < .001) and Running Speed/Agility
      (P = .005). Specifically in Balance, 21 (70%) participants performed below or
      well-below average. Participants with a non-astrocytoma performed significantly
      lower than norms in all areas, independent of age at diagnosis. Survivors with
      tumors infiltrating the vermis demonstrated significantly lower Body Coordination
      than norms (P < .001). CONCLUSIONS: Pediatric survivors of PFBTs demonstrated
      decreased physical functioning, most notably in Balance. These data underscore
      the need for further research and implementation of physical activity programs
      aimed specifically at approaches to minimize physical limitations.

PMID- 24305708
TI  - Where are we now? And where are we going? A report from the Accelerate Brain
      Cancer Cure (ABC2) low-grade glioma research workshop.
AB  - Diffuse gliomas consist of both low- and high-grade varieties, each with distinct
      morphological and biological features. The often extended periods of relative
      indolence exhibited by low-grade gliomas (LGG; WHO grade II) differ sharply from
      the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO
      grade IV). Nevertheless, until recently, the molecular foundations underlying
      this stark biological contrast between glioma variants remained largely unknown.
      The discoveries of distinctive and highly recurrent genomic and epigenomic
      abnormalities in LGG have both informed a more accurate classification scheme and
      pointed to viable avenues for therapeutic development. As such, the field of
      neuro-oncology now seems poised to capitalize on these gains to achieve
      significant benefit for LGG patients. This report will briefly recount the
      proceedings of a workshop held in January 2013 and hosted by Accelerate Brain
      Cancer Cure (ABC(2)) on the subject of LGG. While much of the meeting covered
      recent insights into LGG biology, its focus remained on how best to advance the
      clinical management, whether by improved preclinical modeling, more effective
      targeted therapeutics and clinical trial design, or innovative imaging
      technology. 

PMID- 24305709
TI  - Tight junction protein claudin-1 is differentially expressed in craniopharyngioma
      subtypes and indicates invasive tumor growth.
AB  - BACKGROUND: Claudins are tight junction proteins expressed in epithelial tissues
      that play important roles in cell polarity and adhesion. Altered distribution of
      claudin-1(CLDN1) affects cell mobility and tumor invasiveness. Craniopharyngiomas
      (CPs) represent epithelial tumors of the sellar region, consisting of
      adamantinomatous (adaCP) and papillary (papCP) variants. Their tendency to
      infiltrate surrounding brain structures complicates successful surgery. Reliable
      markers are required to predict tumor behavior and to establish individualized
      treatment protocols. METHODS: We describe the distribution pattern of CLDN1 in a
      large cohort of 66 adaCPs, 21 papCPs, and 24 Rathke's cleft cyst (RCC) cases
      using immunohistochemistry. CLDN1 mRNA levels were analyzed with qRT-PCR in 33 CP
      samples. The impact on the migration potential was studied in primary adaCP cell
      cultures (n = 11) treated with small interfering RNA (siRNA) for CLDN1.
      Furthermore, CLDN1 distribution patterns and expression levels were compared
      between invasive (n = 16) and noninvasive (n = 17) tumor groups. RESULTS: PapCPs
      and RCCs exhibited a distinct homogenous and membranous expression pattern,
      whereas CLDN1 immunoreactivity appeared weaker and more heterogeneous in adaCPs.
      In the latter cases, whirl-like cell clusters showed complete absence of CLDN1.
      mRNA analysis confirmed reduced CLDN1 levels in adaCPs versus papCPs.
      Interestingly, invasive tumors exhibited significantly lower CLDN1 expression
      compared with noninvasive counterparts regardless of CP subtype. Accordingly,
      siRNA treatment for CLDN1 altered tumor cell migration in vitro. CONCLUSION:
      CLDN1 represents a novel marker in the differential diagnosis of CP variants and
      RCCs. Low CLDN1 expression levels correlate with an invasive CP growth pattern
      and may serve as a prognostic marker.

PMID- 24305710
TI  - A novel tumor-promoting role for nuclear factor IA in glioblastomas is mediated
      through negative regulation of p53, p21, and PAI1.
AB  - Background Nuclear factor IA (NFIA), a transcription factor and essential
      regulator in embryonic glial development, is highly expressed in human
      glioblastoma (GBM) compared with normal brain, but its contribution to GBM and
      cancer pathogenesis is unknown. Here we demonstrate a novel role for NFIA in
      promoting growth and migration of GBM and establish the molecular mechanisms
      mediating these functions. Methods To determine the role of NFIA in glioma, we
      examined the effects of NFIA in growth, proliferation, apoptosis, and migration.
      We used gain-of-function (overexpression) and loss-of-function (shRNA knockdown)
      of NFIA in primary patient-derived GBM cells and established glioma cell lines in
      culture and in intracranial xenografts in mouse brains. Results Knockdown of
      native NFIA blocked tumor growth and induced cell death and apoptosis.
      Complementing this, NFIA overexpression accelerated growth, proliferation, and
      migration of GBM in cell culture and in mouse brains. These NFIA tumor-promoting
      effects were mediated via transcriptional repression of p53, p21, and plasminogen
      activator inhibitor 1 (PAI1) through specific NFIA-recognition sequences in their
      promoters. Importantly, the effects of NFIA on proliferation and apoptosis were
      independent of TP53 mutation status, a finding especially relevant for GBM, in
      which TP53 is frequently mutated. Conclusion NFIA is a modulator of GBM growth
      and migration, and functions by distinct regulation of critical oncogenic
      pathways that govern the malignant behavior of GBM. 

PMID- 24305712
TI  - Increased sensitivity to radiochemotherapy in IDH1 mutant glioblastoma as
      demonstrated by serial quantitative MR volumetry.
AB  - BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations have been linked to
      favorable outcomes in patients with glioblastoma multiforme (GBM). Recent in
      vitro experiments suggest that IDH1 mutation sensitizes tumors to radiation
      damage. We hypothesized that radiographic treatment response would be
      significantly different between IDH1 mutant versus wild-type GBMs after
      radiotherapy (RT) and concurrent temozolomide (TMZ). METHODS: A total of 39 newly
      diagnosed GBM patients with known IDH1 mutational status (10 IDH1 mutants), who
      followed standard therapy and had regular post-contrast T1W (T1+C) and T2W/ fluid
      attenuated inversion recovery (FLAIR) images in the 6-month period after starting
      RT, were enrolled. The volume of contrast-enhancing and FLAIR hyperintensity were
      calculated from each scan. Linear and polynomial regression techniques were used
      to estimate the rate of change and temporal patterns in tumor volumes. RESULTS:
      IDH1 mutant GBMs demonstrated a favorable response to RT/TMZ in the study period,
      as demonstrated by 10 of 10 mutants showing radiographic response (decreasing
      V(T1+C)), compared with 13 of 29 wild-types (P < .001). During the study period,
      V(T1+C) and V(FLAIR) changed at -3.6% per week and +0.6% per week in IDH1 mutant
      tumors, respectively, as compared with +0.8% per week and +5.2% per week in IDH1
      wild-type tumors (P = .0076 and P = .0118, respectively). Amongst the
      radiographic responders, IDH1 mutant GBMs still demonstrated significant
      progression-free and overall survival benefit. Aggregated tumor kinetics by group
      showed significant lower rate in IDH1 mutant GBMs in specific periods: >105 days
      for V(FLAIR) and 95-120 and >150 days for V(T1+C) from starting RT/TMZ.
      CONCLUSIONS: The current study supports the hypothesis that IDH1 mutant GBMs are
      more sensitive to radiochemotherapy than IDH1 wild-type GBMs.

PMID- 24305711
TI  - The rationale for targeted therapies in medulloblastoma.
AB  - Medulloblastoma (MB) is the most frequent malignant brain tumor in children.
      Patients with MB who are classified as having high-risk disease or those with
      recurrent disease respond poorly to current therapies and have an increased risk
      of MB-related mortality. Preclinical studies and molecular profiling of MB tumors
      have revealed upregulation or activation of several key signaling pathways such
      as the sonic hedgehog and WNT pathways. Although the exact mechanisms underlying
      MB tumorigenesis remain poorly understood, inhibiting these key pathways with
      molecularly targeted therapies represents an important approach to improving MB
      outcomes. Several molecularly targeted therapies are already under clinical
      investigation in MB patients. We discuss current preclinical and clinical data,
      as well as data from clinical trials of targeted therapies that are either
      ongoing or in development for MB. 

PMID- 24305713
TI  - MDA-9/syntenin is a key regulator of glioma pathogenesis.
AB  - BACKGROUND: The extraordinary invasiveness of human glioblastoma multiforme (GBM)
      contributes to treatment failure and the grim prognosis of patients diagnosed
      with this tumor. Consequently, it is imperative to define further the cellular
      mechanisms that control GBM invasion and identify promising novel therapeutic
      targets. Melanoma differentiation associated gene-9 (MDA-9/syntenin) is a highly
      conserved PDZ domain-containing scaffolding protein that promotes invasion and
      metastasis in vitro and in vivo in human melanoma models. To determine whether
      MDA-9/syntenin is a relevant target in GBM, we investigated its expression in
      tumor samples and involvement in GBM invasion and angiogenesis. MATERIALS: We
      assessed MDA-9/syntenin levels in available databases, patient tumor samples, and
      human-derived cell lines. Through gain-of-function and loss-of-function studies,
      we analyzed changes in invasion, angiogenesis, and signaling in vitro. We used
      orthotopic xenografts with GBM6 cells to demonstrate the role of MDA-9/syntenin
      in GBM pathogenesis in vivo. RESULTS: MDA-9/syntenin expression in high-grade
      astrocytomas is significantly higher than normal tissue counterparts. Forced
      overexpression of MDA-9/syntenin enhanced Matrigel invasion, while knockdown
      inhibited invasion, migration, and anchorage-independent growth in soft agar.
      Moreover, overexpression of MDA-9/syntenin increased activation of c-Src, p38
      mitogen-activated protein kinase, and nuclear factor kappa-B, leading to elevated
      expression of matrix metalloproteinase 2 and secretion of interleukin-8 with
      corresponding changes observed upon knockdown. GBM6 cells that stably express
      small hairpin RNA for MDA-9/syntenin formed smaller tumors and had a less
      invasive phenotype in vivo. CONCLUSIONS: Our findings indicate that MDA
      9/syntenin is a novel and important mediator of invasion in GBM and a key
      regulator of pathogenesis, and we identify it as a potential target for anti
      invasive treatment in human astrocytoma.

PMID- 24305714
TI  - High-throughput microRNA profiling of pediatric high-grade gliomas.
AB  - BACKGROUND: High-grade gliomas (HGGs) account for 15% of all pediatric brain
      tumors and are a leading cause of cancer-related mortality and morbidity.
      Pediatric HGGs (pHGGs) are histologically indistinguishable from their
      counterpart in adulthood. However, recent investigations indicate that
      differences occur at the molecular level, thus suggesting that the molecular path
      to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs)
      have been identified as key molecules in gene expression regulation, both in
      development and in cancer. miRNAs have been investigated in adult high-grade
      gliomas (aHGGs), but scant information is available for pHGGs. METHODS: We
      explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen
      and paraffin-embedded tissue, by high-throughput miRNA profiling. We also
      evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell
      line. RESULTS: Comparison of miRNA expression patterns in formalin versus frozen
      specimens resulted in high correlation between both types of samples. The
      analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an
      overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we
      highlighted a possible quenching function of miR-17-92 cluster on its target gene
      PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog
      in pHGG. CONCLUSIONS: Our results suggest that microRNA profiling represents a
      tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster
      sustains pHGG.

PMID- 24305715
TI  - Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in
      childhood chordomas.
AB  - BACKGROUND: Chordomas are slow-growing tumors and most commonly involve the
      sacrum and clivus. Multiple recurrences are frequent. Childhood chordomas are
      rare and often show exceptionally aggressive behavior, resulting in short
      survival and a high incidence of metastatic spread. OBJECTIVE: This study
      examined the histologic features and immunohistochemical profile of pediatric
      chordomas and compared them with their adult counterparts. METHODS: Nine
      pediatric and 13 adult cases were included in the study. Childhood chordomas were
      classified into conventional, atypical, and poorly differentiated types.
      Immunohistochemistry was performed for cytokeratin, epithelial membrane antigen,
      vimentin, S100, brachyury, p53, INI1, epidermal growth factor receptor (EGFR),
      and CD117. Cytogenetic analyses were performed in a subset of tumors for
      SMARCB1/INI1 locus on 22q chromosome by fluorescent in situ hybridization (FISH)
      and analysis of the SMARCB1/INI1 gene sequence. RESULTS: All tumors showed
      expression of cytokeratin, epithelial membrane antigen, S100, vimentin,
      brachyury, and EGFR. Atypical morphology, p53 expression, higher MIB-1 labelling
      index (LI), and INI1 loss were more frequently seen in pediatric chordomas as
      compared with adults. None of the tumors showed CD117 expression. No point
      mutation in the SMARCB1/INI1 gene was noted in the tumors examined; however, 4
      pediatric and 1 adult chordoma showed loss of this locus on FISH analysis.
      CONCLUSIONS: A subset of pediatric chordomas with atypical histomorphologic
      features needs to be identified, as they behave in an aggressive manner and
      require adjuvant therapy. Pediatric chordomas more frequently show p53
      expression, INI1 loss, and higher MIB-1 LI as compared with adults, whereas EGFR
      expression is common to both.

PMID- 24305716
TI  - Diagnosing relapse in children's brain tumors using metabolite profiles.
AB  - BACKGROUND: Malignant brain tumors in children generally have a very poor
      prognosis when they relapse and improvements are required in their management. It
      can be difficult to accurately diagnose abnormalities detected during tumor
      surveillance, and new techniques are required to aid this process. This study
      investigates how metabolite profiles measured noninvasively by (1)H magnetic
      resonance spectroscopy (MRS) at relapse reflect those at diagnosis and may be
      used in this monitoring process. METHODS: Single-voxel MRS (1.5 T, point-resolved
      spectroscopy, echo time 30 ms, repetition time 1500 ms was performed on 19
      children with grades II-IV brain tumors during routine MRI scans prior to
      treatment for a suspected brain tumor and at suspected first relapse. MRS was
      analyzed using TARQUIN software to provide metabolite concentrations. Paired
      Student's t-tests were performed between metabolite profiles at diagnosis and at
      first relapse. RESULTS: There was no significant difference (P > .05) in the
      level of any metabolite, lipid, or macromolecule from tumors prior to treatment
      and at first relapse. This was true for the whole group (n = 19), those with a
      local relapse (n = 12), and those with a distant relapse (n = 7). Lipids at 1.3
      ppm were close to significance when comparing the level at diagnosis with that at
      distant first relapse (P = .07, 6.5 vs 12.9). In 5 cases the MRS indicative of
      tumor preceded a formal diagnosis of relapse. CONCLUSIONS: Tumor metabolite
      profiles, measured by MRS, do not change greatly from diagnosis to first relapse,
      and this can aid the confirmation of the presence of tumor.

PMID- 24305717
TI  - Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent
      brain tumors.
AB  - BACKGROUND: Both (18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) and (18)F
      fluoroethyltyrosine ((18)F-FET) have already been used successfully for imaging
      of brain tumors. The aim of this study was to evaluate differences between these
      2 promising tracers to determine the consequences for imaging protocols and the
      interpretation of findings. METHODS: Forty minutes of dynamic PET imaging were
      performed on 2 consecutive days with both (18)F-DOPA and (18)F-FET in patients
      with recurrent low-grade astrocytoma (n = 8) or high-grade glioblastoma (n = 8).
      Time-activity-curves (TACs), standardized uptake values (SUVs) and compartment
      modeling of both tracers were analyzed, respectively. RESULTS: The TAC of DOPA
      PET peaked at 8 minutes p.i. with SUV 5.23 in high-grade gliomas and 10 minutes
      p.i. with SUV 4.92 in low-grade gliomas. FET-PET peaked at 9 minutes p.i. with
      SUV 3.17 in high-grade gliomas and 40 minutes p.i. with SUV 3.24 in low-grade
      gliomas. Neglecting the specific uptake of DOPA into the striatum, the tumor-to
      brain and tumor-to-blood ratios were higher for DOPA-PET. Kinetic modeling
      demonstrated a high flow constant k1 (mL/ccm/min), representing cellular
      internalization through AS-transporters, for DOPA in both high-grade (k1 = 0.59)
      and low-grade (k1 = 0.55) tumors, while lower absolute values and a relevant
      dependency from tumor-grading (high-grade k1 = 0.43; low-grade k1 = 0.33) were
      observed with FET. CONCLUSIONS: DOPA-PET demonstrates superior contrast ratios
      for lesions outside the striatum, but SUVs do not correlate with grading. FET-PET
      can provide additional information on tumor grading and benefits from lower
      striatal uptake but presents lower contrast ratios and requires prolonged imaging
      if histology is not available in advance due to a more variable time-to-peak.

PMID- 24305718
TI  - Amide proton transfer imaging of adult diffuse gliomas: correlation with
      histopathological grades.
AB  - BACKGROUND: Amide proton transfer (APT) imaging is a novel molecular MRI
      technique to detect endogenous mobile proteins and peptides through chemical
      exchange saturation transfer. We prospectively assessed the usefulness of APT
      imaging in predicting the histological grade of adult diffuse gliomas. METHODS:
      Thirty-six consecutive patients with histopathologically proven diffuse glioma
      (48.1 +/- 14.7 y old, 16 males and 20 females) were included in the study. APT
      MRI was conducted on a 3T clinical scanner and was obtained with 2 s saturation
      at 25 saturation frequency offsets omega = -6 to +6 ppm (step 0.5 ppm). deltaB0
      maps were acquired separately for a point-by-point deltaB0 correction. APT signal
      intensity (SI) was defined as magnetization transfer asymmetry at 3.5 ppm:
      magnetization transfer ratio (MTR)asym = (S[-3.5 ppm] - S[+3.5 ppm])/S0. Regions
      of interest were carefully placed by 2 neuroradiologists in solid parts within
      brain tumors. The APT SI was compared with World Health Organization grade, Ki-67
      labeling index (LI), and cell density. RESULTS: The mean APT SI values were 2.1
      +/- 0.4% in grade II gliomas (n = 8), 3.2 +/- 0.9% in grade III gliomas (n = 10),
      and 4.1 +/- 1.0% in grade IV gliomas (n = 18). Significant differences in APT
      intensity were observed between grades II and III (P < .05) and grades III and IV
      (P < .05), as well as between grades II and IV (P < .001). There were positive
      correlations between APT SI and Ki-67 LI (P = .01, R = 0.43) and between APT SI
      and cell density (P < .05, R = 0.38). The gliomas with microscopic necrosis
      showed higher APT SI than those without necrosis (P < .001). CONCLUSIONS: APT
      imaging can predict the histopathological grades of adult diffuse gliomas.

PMID- 24305719
TI  - IDH1 mutant malignant astrocytomas are more amenable to surgical resection and
      have a survival benefit associated with maximal surgical resection.
AB  - BACKGROUND: IDH1 gene mutations identify gliomas with a distinct molecular
      evolutionary origin. We sought to determine the impact of surgical resection on
      survival after controlling for IDH1 status in malignant astrocytomas-World Health
      Organization grade III anaplastic astrocytomas and grade IV glioblastoma.
      METHODS: Clinical parameters including volumetric assessment of preoperative and
      postoperative MRI were recorded prospectively on 335 malignant astrocytoma
      patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status
      was assessed by sequencing and immunohistochemistry. RESULTS: IDH1 mutation was
      independently associated with complete resection of enhancing disease (93%
      complete resections among mutants vs 67% among wild-type, P < .001), indicating
      IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor
      on survival differed between IDH1 wild-type and mutant tumors. Complete resection
      of enhancing disease among IDH1 wild-type tumors was associated with a median
      survival of 19.6 months versus 10.7 months for incomplete resection; however, no
      survival benefit was observed in association with further resection of
      nonenhancing disease (minimization of total tumor volume). In contrast, IDH1
      mutants displayed an additional survival benefit associated with maximal
      resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not
      reached for <5 cc, P = .025). CONCLUSIONS: The survival benefit associated with
      surgical resection differs based on IDH1 genotype in malignant astrocytic
      gliomas. Therapeutic benefit from maximal surgical resection, including both
      enhancing and nonenhancing tumor, may contribute to the better prognosis observed
      in the IDH1 mutant subgroup. Thus, individualized surgical strategies for
      malignant astrocytoma may be considered based on IDH1 status.

PMID- 24305720
TI  - Differential patterns of NOTCH1-4 receptor expression are markers of glioma cell
      differentiation.
AB  - Background Notch signaling is deregulated in human gliomas and may play a role in
      their malignancy. However, the role of each Notch receptor in glioma cell
      differentiation and progression is not clear. We examined the expression pattern
      of Notch receptors and compared it with differentiation markers in glioma cell
      lines, primary human cultures, and biopsies of different grades. Furthermore, the
      effects of a gamma-secretase inhibitor (GSI) on cell survival were assessed.
      Methods Notch receptors and markers of cellular differentiation were analyzed by
      reverse transcriptase PCR, Western blotting, immunohistochemistry, and
      immunocytochemistry. GSI sensitivity was assessed in both cell lines and primary
      cultures grown as monolayers or tumorspheres, by MTT assay. Results In cell
      lines, Notch1 and Notch2/4 levels paralleled those of glial fibrillary acidic
      protein (GFAP) and vimentin, respectively. In human gliomas and primary cultures,
      Notch1 was moderate/strong in low-grade tumors but weak in glioblastoma
      multiforme (GBM). Conversely, Notch4 increased from astrocytoma grade II to GBM.
      Primary GBM cultures grown in serum (monolayer) showed moderate/high levels of
      CD133, nestin, vimentin, and Notch4 and very low levels of GFAP and Notch1, which
      were reduced in tumorspheres. This effect was drastic for Notch4. GSI reduced
      cell survival with stronger effect in serum, whilst human primary cultures showed
      different sensitivity. Conclusion Data from cell lines and human gliomas suggest
      a correlation between expression of Notch receptors and cell differentiation.
      Namely, Notch1 and Notch4 are markers of differentiated and less differentiated
      glioma cells, respectively. We propose Notch receptors as markers of glioma
      grading and possible prognostic factors. 

PMID- 24305721
TI  - Challenges for the functional diffusion map in pediatric brain tumors.
AB  - BACKGROUND: The functional diffusion map (fDM) has been suggested as a tool for
      early detection of tumor treatment efficacy. We aim to study 3 factors that could
      act as potential confounders in the fDM: areas of necrosis, tumor grade, and
      change in tumor size. METHODS: Thirty-four pediatric patients with brain tumors
      were enrolled in a retrospective study, approved by the local ethics committee,
      to examine the fDM. Tumors were selected to encompass a range of types and
      grades. A qualitative analysis was carried out to compare how fDM findings may be
      affected by each of the 3 confounders by comparing fDM findings to clinical image
      reports. RESULTS: Results show that the fDM in areas of necrosis do not
      discriminate between treatment response and tumor progression. Furthermore, tumor
      grade alters the behavior of the fDM: a decrease in apparent diffusion
      coefficient (ADC) is a sign of tumor progression in high-grade tumors and
      treatment response in low-grade tumors. Our results also suggest using only tumor
      area overlap between the 2 time points analyzed for the fDM in tumors of varying
      size. CONCLUSIONS: Interpretation of fDM results needs to take into account the
      underlying biology of both tumor and healthy tissue. Careful interpretation of
      the results is required with due consideration to areas of necrosis, tumor grade,
      and change in tumor size.

PMID- 24305722
TI  - Comparison of visual and semiquantitative analysis of 18F-FDOPA-PET/CT for
      recurrence detection in glioblastoma patients.
AB  - BACKGROUND: Amino acid transport imaging with 18F-FDOPA PET is increasingly used
      for detection of glioblastoma recurrence. However, a standardized image
      interpretation for 18F-FDOPA brain PET studies has not yet been established. This
      study compares visual and semiquantitative analysis parameters for detection of
      tumor recurrence and correlates them with progression-free survival (PFS).
      METHODS: One-hundred ten patients (72 male:38 female) with suspected tumor
      recurrence who underwent 18F-FDOPA PET imaging were studied. PET scans were
      analyzed visually (5-point scale) and semiquantitatively (lesion-to-striatum- and
      lesion- to-normal-brain-tissue ratios using both SUV(mean) and SUV(max)).
      Accuracies for recurrence detection were calculated using histopathology and
      clinical follow-up for validation. Receiving operator characteristic and Kaplan
      Meier survival analysis were performed to derive imaging-based prediction of PFS
      and overall survival (OS). RESULTS: Accuracies for detection of glioblastoma
      recurrence were similar for visual (82%) and semiquantitative (range, 77%-82%)
      analysis. Both visual and semiquantitative indices were significant predictors of
      PFS, with mean lesion-to normal brain tissue ratios providing the best
      discriminator (mean survival, 39.4 vs 9.3 months; P < .001). None of the
      investigated parameters was predictive for OS. CONCLUSIONS: Both visual and
      semiquantitative indices detected glioblastoma recurrence with high accuracy and
      were predictive for PFS. Lesion-to-normal-tissue ratios were the best
      discriminators of PFS; however, none of the investigated parameters predicted OS.
      These retrospectively established analysis parameters need to be confirmed
      prospectively.

PMID- 24305724
TI  - The anatomy and function of Cleland's ligaments.
AB  - The cutaneous ligaments of the digits have been recognized by anatomists for
      several centuries, but the best known description is that of John Cleland.
      Subsequent varying descriptions of their morphology have resulted in the surgical
      community having an imprecise view of their structure and dynamic function. We
      micro-dissected 24 fresh frozen fingers to analyze the individual components of
      Cleland's ligamentous system. Arising from the proximal interphalangeal (PIP)
      joint, proximal, and sometimes middle phalanx, we found strong ligaments that ran
      proximally (PIP-P) and distally (PIP-D). On each side of each finger there was a
      PIP-P ligament present, which passed obliquely from the lateral side of the
      proximal and sometimes middle phalanx towards its insertion into the skin at the
      level of the proximal phalanx. The distal (PIP-D) ligaments were found to pass
      obliquely distally on the radial and ulnar aspects of the digit towards cutaneous
      insertions around the middle phalanx. A similar arrangement exists more distally
      with fibres originating from the DIP joint and middle phalanx (the DIP-P pass
      obliquely proximally, and the DIP-D, distally). Each individual PIP ligament
      consisted of three different layers originating from fibres overlying the flexor
      tendon sheath, periosteum or joint capsule, and extensor expansion. Ligaments
      arising at the DIP joint had two layers equivalent to the anterior two layers of
      the proximal ligaments. Cleland's ligaments act as skin anchors maintaining the
      skin in a fixed relationship to the underlying skeleton during motion and
      functional tasks. They also prevent the skin from 'bagging', protect the
      neurovascular bundle, and create a gliding path for the lateral slips of the
      extensor tendon. 

PMID- 24305723
TI  - Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.
AB  - BACKGROUND: Tumors affecting the head, neck, and brain account for significant
      morbidity and mortality. The curative efficacy of radiotherapy for these tumors
      is well established, but radiation carries a significant risk of neurologic
      injury. So far, neuroprotective therapies for radiation-induced brain injury are
      still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)
      170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel,
      protected mice from radiation-induced brain injury. METHODS: Mice were treated
      with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced
      brain injury was assessed by MRI scans and a Morris water maze.
      Pathophysiological change of the brain was measured by immunofluorescence. Gene
      and protein expressions of Kv1.3 and inflammatory factors were measured by
      quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western
      blot analyses. Kv currents were recorded in the whole-cell configuration of the
      patch-clamp technique. RESULTS: Radiation increased Kv1.3 mRNA and protein
      expression in microglia. Genetic silencing of Kv1.3 by specific short
      interference RNAs or pharmacological blockade with ShK-170 suppressed radiation
      induced production of the proinflammatory factors interleukin-6, cyclooxygenase
      2, and tumor necrosis factor-alpha by microglia. ShK-170 also inhibited
      neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis
      by increasing the proliferation of neural progenitor cells. CONCLUSIONS: The
      therapeutic effect of ShK-170 is mediated by suppression of microglial activation
      and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting
      proliferation of neural progenitor cells.

PMID- 24305725
TI  - Changes in ligating abilities of the singlet and triplet states of normal,
      abnormal and remote N-heterocyclic carbenes depending on their aromaticities.
AB  - Quantum chemical calculations at B3LYP/aug-cc-pVTZ level about singlet N
      heterocyclic carbene (NHC) ligands, imidazol-2-ylidene, imidazol-4-ylidene,
      pyrazol-3-ylidene and pyrazol-4-ylidene, and their protonated analogues show that
      they are considerably aromatic except for pyrazol-3-ylidene. This result is
      experimentally verified by approximately five thousand NHC transition metal
      complexes retrieved from the Cambridge Structural Database (CSD). CSD search
      discloses that NHCs can participate in pi-stacking interactions, albeit scarce.
      Geometry-based HOMA and electronic aromaticity index FLU rather than NICS provide
      a satisfactory description of the bonding situations in NHC ligands. Singlet
      state of the normal NHC has electron-deficient aromaticity as compared to those
      of the abnormal and remote NHCs. Depending on the transition from the singlet to
      triplet state, NHCs become electron-deficient ligands except for remote NHC.
      Computational studies regarding electronic nature of free NHC ligands show that
      the pi-electronic population of the formally vacant ppi orbital on the carbene
      atoms in abnormal and remote NHC is occurred as a result of the aromaticity of
      NHCs, not as a result of the direct electron donation from LP-orbitals of N atoms
      to carbene atom according to putative push-pull effect used in understanding the
      electronic stabilization of normal NHC. Increase in the aromaticity raises sigma
      donating ability of both imidazol- and pyrazol-based NHC ligands. Free abnormal
      and remote NHC ligands have higher sigma-donation ability than normal NHC
      ligands. The lack of sigma-donating ability of normal NHC is compensated by its
      relatively high pi-accepting ability, whereas pi-back donation abilities of
      abnormal and remote NHCs are prohibited by their almost fully occupied pi
      orbitals. Aromaticities of the triplet NHC ligands are higher than that of the
      lowest-lying triplet state of benzene. Increase in the aromaticity of NHC ligands
      decreases van der Waals shortening in TM-NHC bonds mainly due to diminishing
      dative character of these bonds. 

PMID- 24305726
TI  - Protection of patients' right to privacy in clinical photographs, video, and
      detailed case descriptions.

PMID- 24305727
TI  - Bio-inspired nanocatalysts for the oxygen reduction reaction.
AB  - Electrochemical conversions at fuel cell electrodes are complex processes. In
      particular, the oxygen reduction reaction has substantial overpotential limiting
      the electrical power output efficiency. Effective and inexpensive catalytic
      interfaces are therefore essential for increased performance. Taking inspiration
      from enzymes, earth-abundant metal centres embedded in organic environments
      present remarkable catalytic active sites. Here we show that these enzyme
      inspired centres can be effectively mimicked in two-dimensional metal-organic
      coordination networks self-assembled on electrode surfaces. Networks consisting
      of trimesic acid and bis-pyridyl-bispyrimidine coordinating to single iron and
      manganese atoms on Au(111) effectively catalyse the oxygen reduction and reveal
      distinctive catalytic activity in alkaline media. These results demonstrate the
      potential of surface-engineered metal-organic networks for electrocatalytic
      conversions. Specifically designed coordination complexes at surfaces inspired by
      enzyme cofactors represent a new class of nanocatalysts with promising
      applications in electrocatalysis. 

PMID- 24305728
TI  - Immunization status in children with inflammatory bowel disease.
AB  - Inflammatory bowel diseases have an increased risk of infections due to
      immunosuppressive therapies. To report the immunization status according to
      previous recommendations and the reasons explaining a delay, a questionnaire was
      filled in by the pediatric gastroenterologist, concerning outpatients, in six
      tertiary centers and five local hospitals, in a study, from May to November 2011.
      One hundred and sixty-five questionnaires were collected, of which 106 Crohn's
      diseases, 41 ulcerative colitis, and 17 indeterminate colitis. Sex ratio was
      87:78 M/F. Median age was 14.4 years old (4.2-20.0). One hundred and nine
      patients (66 %) were receiving or had received an immunosuppressive therapy
      (azathioprine, infliximab, methotrexate, or prednisone). Vaccines were up to date
      according to the vaccine schedule of French recommendations in 24 % of cases and
      according to the recommendations for inflammatory bowel disease in 4 % of cases.
      Coverage by vaccine was the following: diphtheria-tetanus-poliomyelitis 87 %,
      hepatitis B 38 %, pneumococcus 32 %, and influenza 22 %. Immunization delay
      causes were as follows: absence of proposal 58 %, patient refusal 41 %, fear of
      side effects 33 %, and fear of disease activation 5 %. Therefore, immunization
      coverage is insufficient in children with inflammatory bowel disease, due to
      simple omission or to refusal. A collaboration with the attending physicians and
      a targeted information are necessary. 

PMID- 24305729
TI  - Improving bioavailability with a novel isotretinoin formulation (isotretinoin
      Lidose).
AB  - Current practice guidelines recommend administration of oral isotretinoin with
      high-fat meals, which may pose issues with patient compliance. Isotretinoin
      Lidose (EpurisTM), approved by Health Canada in November 2012 and scheduled for
      commercial release June 2013, is based on novel lipid encapsulation technology
      (Lidose(r)) to enclose isotretinoin, thereby increasing drug absorption during
      fasted states. An open label, single dose randomized crossover study demonstrated
      pharmacokinetic bioequivalence of isotretinoin-Lidose to standard isotretinoin
      formulations during fed states, with significantly greater absorption during
      fasting. Isotretinoin-Lidose, may lead to more consistent plasma levels of
      isotretinoin during variable dietary conditions, providing the potential for
      enhanced patient outcomes. 

PMID- 24305730
TI  - Treatment of infantile hemangiomas with beta-blockers: a review.
AB  - Infantile hemangiomas (IH) are the most common tumors occurring in early
      childhood, with a prevalence of approximately 5-10% of infants. While the natural
      history of IH is to spontaneously involute, a significant minority of IH require
      therapy with the aim to prevent disfigurement, functional impairment, or
      ulceration. In 2008, propranolol, a non-selective beta (beta)-blocker, was
      reported to be highly effective in treating IH. Since that time there have been
      more than 200 articles published regarding the efficacy and potential toxicity of
      beta-blockers, both systemic and topical, for the treatment of IH. Based on these
      finding, beta-blockers appear to be highly effective in treating IH and are well
      tolerated, though side effects have been reported. When therapy is appropriately
      monitored, beta-blockers have been proven to be a safer and superior alternative
      to systemic steroids. 

PMID- 24305731
TI  - Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo
      imaging.
AB  - Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic
      resonance imaging due to the impressive contrast ability. However, the reported
      Mn-based NPs possess low relaxivity and there are no immunotoxicity data
      regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh
      relaxivity of water protons of 8.26 mM(-1) s(-1) from the Mn3O4 NPs synthesized
      by a simple and green technique, which is twice higher than that of commercial
      gadolinium (Gd)-based contrast agents (4.11 mM(-1) s(-1)) and the highest value
      reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4
      NPs biocompatibilities both in vitro and in vivo are satisfactory based on
      systematical studies of the intrinsic toxicity including cell viability of human
      nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in
      cells and in vivo immunotoxicity. These findings pave the way for the practical
      clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

PMID- 24305732
TI  - Integrated architecture for the electrical detection of plasmonic resonances
      based on high electron mobility photo-transistors.
AB  - We report the design of an integrated platform for on-chip electrical
      transduction of the surface plasmon resonance supported by a nanostructured metal
      grating. The latter is fabricated on the active area of a GaAs/AlGaAs photo-HEMT
      and simultaneously works as the electronic gate of the device. The gold plasmonic
      crystal has a V-groove profile and has been designed by numerical optical
      simulations. By showing that the numerical models accurately reproduce the
      phototransistors experimental response, we demonstrate that the proposed
      architecture is suitable for the development of a new class of compact and
      scalable SPR sensors. 

PMID- 24305733
TI  - Fish in chips: an automated microfluidic device to study drug dynamics in vivo
      using zebrafish embryos.
AB  - Interference of the Hedgehog (Hh) signaling pathway by cyclopamine leads to
      abnormal embryonic development. We monitor this dynamical drug effect in
      zebrafish embryos with highly precise microenvironment control using an
      integrated microfluidic device. This chip-based platform, which is programmable
      and automated, greatly facilitates the accuracy and reproducibility of the in
      vivo assays. 

PMID- 24305734
TI  - Class III compensation, represented by KRP2 overexpression, depends on V-ATPase
      activity in proliferative cells.
AB  - Compensation refers to an increase in cell size when the cell number is
      significantly decreased due to the mutation or gain of function of a gene that
      negatively affects the cell cycle. Given the importance of coordinated growth
      during organogenesis in both animal and plant systems, compensation is important
      to understand the mechanism of size regulation. In leaves, cell division precedes
      cell differentiation (which involves cell expansion); therefore, a decrease in
      cell number triggers enhanced cell expansion (compensated cell expansion;
      hereafter, CCE). Functional analyses of genes for which a loss or gain of
      function triggers compensation have increased our understanding of the molecular
      mechanisms underlying the decrease in cell number. Nevertheless, the mechanisms
      that induce enhanced cell expansion (the link between cell cycling and
      expansion), as well as the cellular machinery mediating CCE, have not been
      characterized. We recently characterized an important pathway involved in cell
      enlargement in KRP2-overexpressing plants. Here, we discuss the potential axial
      role of plant KRPs in triggering enlargement in cells with meristematic features.

PMID- 24305735
TI  - Evaluating DAPK as a therapeutic target.
AB  - Death associated protein kinase 1 (DAPK) is an important serine/theoreine kinase
      involved in various cellular processes such as apoptosis, autophagy and
      inflammation. DAPK expression and activity are misregulated in multiple diseases
      including cancer, neuronal death, stoke, et al. Methylation of the DAPK gene is
      common in many types of cancer and can lead to loss of DAPK expression. In this
      review, we summarize the pathological status and functional roles of DAPK in
      disease and compare the published reagents that can manipulate the expression or
      activity of DAPK. The pleiotropic functions of DAPK make it an intriguing target
      and the barriers and opportunities for targeting DAPK for future clinical
      application are discussed. 

PMID- 24305736
TI  - A 1.8-Mb-reduced Streptomyces clavuligerus genome: relevance for secondary
      metabolism and differentiation.
AB  - A large part (21%) of the wild-type Streptomyces clavuligerus genome is located
      in a 1.8-Mb megaplasmid that greatly influences secondary metabolites
      biosynthesis even if the secondary metabolites are chromosomally encoded. The
      megaplasmid copy number may change depending on the nutritional and environmental
      conditions. The S. clavuligerus oppA2::aph mutant described by Lorenzana et al.
      (2004) does not form aerial mycelium, spores, and clavulanic acid, but
      overproduces holomycin. Transcriptomic studies, polymerase chain reactions (PCR),
      qPCR, and RT-qPCR analysis showed that S. clavuligerus oppA2::aph has a
      drastically reduced number of copies (about 25,000-fold lower than the parental
      strain) of plasmids pSCL1 (10.5 kb), pSCL2 (149.4 kb), and the megaplasmid pSCL4
      (1.8 Mb). To clarify the role of the linear plasmids and the function of OppA2 in
      S. clavuligerus oppA2::aph we constructed oppA2 mutants which contained: (1) a
      normal copy number of the linear plasmids, (2) completely lack of the linear
      plasmids, and (3) a parA-parB pSCL4 mutant that resulted in lack of pSCL4. In
      addition, a strain with a functional oppA2 gene was constructed lacking the
      megaplasmid pSCL4. The results confirmed that the oppA2 gene is essential for
      clavulanic acid production, independently of the presence or absence of linear
      plasmids, but oppA2 has little relevance on differentiation. We demonstrated that
      the lack of sporulation of S. clavuligerus oppA2::aph is due to the absence of
      linear plasmids (particularly pSCL4) and the holomycin overproduction is largely
      due to the lack of pSCL4 and is stimulated by the oppA2 mutation.

PMID- 24305737
TI  - Tracking human sewage microbiome in a municipal wastewater treatment plant.
AB  - Human sewage pollution is a major threat to public health because sewage always
      comes with pathogens. Human sewage is usually received and treated by wastewater
      treatment plants (WWTPs) to control pathogenic risks and ameliorate environmental
      health. However, untreated sewage that flows into water environments may cause
      serious waterborne diseases, as reported in India and Bangladesh. To examine the
      fate of the human sewage microbiome in a local municipal WWTP of Hong Kong, we
      used massively parallel sequencing of 16S rRNA gene to systematically profile
      microbial communities in samples from three sections (i.e., influent, activated
      sludge, and effluent) obtained monthly throughout 1 year. The results indicated
      that: (1) influent sewage bacterial profile reflected the human microbiome; (2)
      human gut bacterial community was the dominant force shaping influent sewage
      bacterial profile; (3) most human sewage bacteria could be effectively removed by
      the WWTP; (4) a total of 75 genera were profiled as potentially pathogenic
      bacteria, most of which were still present in the effluent although at a very low
      level; (5) a grouped pattern of bacterial community was observed among the same
      section samples but a dispersed pattern was found among the different section
      samples; and (6) activated sludge was less affected by the influent sewage
      bacteria, but it showed a significant impact on the effluent bacteria. All of
      these findings provide novel insights toward a mechanistic understanding of the
      fate of human sewage microbiome in the WWTP.

PMID- 24305738
TI  - Posttranscriptional regulation of PhbR, the transcriptional activator of
      polyhydroxybutyrate synthesis, by iron and the sRNA ArrF in Azotobacter
      vinelandii.
AB  - Azotobacter vinelandii is a Gram-negative bacterium able to synthesize poly-beta
      hydroxybutyrate (PHB), a biodegradable plastic of industrial interest. The phbBAC
      operon encodes the enzymes of PHB synthesis and is activated by the
      transcriptional regulator PhbR and the sigma factor RpoS. Iron limitation has
      been previously reported to increase PHB accumulation in A. vinelandii; however,
      the mechanism by which iron controls PHB synthesis is unknown. Under iron
      starvation in Escherichia coli, the RyhB sRNA modulates the translation of genes
      involved in iron homeostasis. ArrF is the RyhB analogue in A. vinelandii and
      similarly increases in quantity during Fe(2+) depletion. In this study, we
      evaluate the effect of iron and ArrF on PHB accumulation, and on phbR and phbBAC
      expression in A. vinelandii strain UW136. Using transcriptional and translational
      fusions of phbR and phbB with gusA reporter gene, we found that iron limitation
      increased the expression of phbBAC at the transcriptional level and
      posttranscriptionally increased the expression of phbR. We also found that the
      ArrF sRNA is a positive regulator of phbR expression at the posttranscriptional
      level. Collectively, these data suggest that iron limitation increases the
      translation of phbR through ArrF. 

PMID- 24305739
TI  - Advanced enzymatic elimination of phenolic contaminants in wastewater: a nano
      approach at field scale.
AB  - The removal of recalcitrant chemicals in wastewater treatment systems is an
      increasingly relevant issue in industrialized countries. The elimination of
      persistent xenobiotics such as endocrine-disrupting chemicals (EDCs) emitted by
      municipal and industrial sewage treatment plants remains an unsolved challenge.
      The existing efficacious physico-chemical methods, such as advanced oxidation
      processes, are resource-intensive technologies. In this work, we investigated the
      possibility to remove phenolic EDCs [i.e., bisphenol A (BPA)] by means of a less
      energy and chemical consuming technology. To that end, cheap and resistant
      oxidative enzymes, i.e., laccases, were immobilized onto silica nanoparticles.
      The resulting nanobiocatalyst produced at kilogram scale was demonstrated to
      possess a broad substrate spectrum regarding the degradation of recalcitrant
      pollutants. This nanobiocatalyst was applied in a membrane reactor at technical
      scale for tertiary wastewater treatment. The system efficiently removed BPA and
      the results of long-term field tests illustrated the potential of fumed silica
      nanoparticles/laccase composites for advanced biological wastewater treatment.

PMID- 24305740
TI  - Analysis of genomic characters reveals that four distinct gene clusters are
      correlated with different functions in Burkholderia cenocepacia AU 1054.
AB  - Possessing three circular chromosomes is a distinct genomic characteristic of
      Burkholderia cenocepacia AU 1054, a clinically important pathogen in cystic
      fibrosis. In this study, base composition, codon usage and functional role
      category were analyzed in the B. cenocepacia AU 1054 genome. Although no bias in
      the base and codon usage was detected between any two chromosomes, function
      differences did exist in the genes of each chromosome. Similar base composition
      and differential functional role categories indicated that genes on these three
      chromosomes were relatively stable and that a proper division of labor was
      established. Based on variations in the base or codon usage, four small gene
      clusters were observed in all of the genes. Multivariate analysis revealed that
      protein hydrophobicity played a predominant role in shaping base usage bias,
      while horizontal gene transfer and the gene expression level were the two most
      important factors that affected the codon usage bias. Interestingly, we also
      found that these gene clusters were correlated with different biological
      functions: (i) 45 pyrimidine-leading-codon preferred genes were predominantly
      involved in regulatory function; (ii) most drug resistance-related genes involved
      in 826 genes that coding for hydrophobic proteins; (iii) most of the 111
      horizontal transfer genes were responsible for genomic plasticity; and (iv) 73
      highly expressed genes (predicted by their codon adaptation index values) showed
      environmental adaptation to cystic fibrosis. Our results showed that genes with
      base or codon usage bias were affected by mutational pressure and natural
      selection, and their functions could contribute to drug assistance and
      transmissible activity in B. cenocepacia. 

PMID- 24305741
TI  - Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles:
      a review.
AB  - Nanotechnology is an emerging branch of science, which has potential to solve
      many problems in different fields. The union of nanotechnology with other fields
      of sciences including physics, chemistry, and biology has brought the concept of
      synthesis of nanoparticles from their respective metals. Till date, many types of
      nanoparticles have been synthesized and being used in different fields for
      various applications. Moreover, copper nanoparticles attract biologists because
      of their significant and broad-spectrum bioactivity. Due to the large surface
      area to volume ratio, copper nanoparticles have been used as potential
      antimicrobial agent in many biomedical applications. But the excess use of any
      metal nanoparticles increase the chance of toxicity to humans, other living
      beings, and environment. In this article, we have critically reviewed the
      bioactivities and cytotoxicity of copper nanoparticles. We have also focused on
      possible mechanism involved in its interaction with microbes. 

PMID- 24305743
TI  - Remote chirality control based on the organocatalytic asymmetric Mannich reaction
      of alpha-thio acetaldehydes.
AB  - Remote chirality control leading to 1,4-difunctionalized compounds such as 1,4
      amino alcohols and 1,4-diamines was achieved by both syn- and anti-selective
      asymmetric Mannich reactions of alpha-thio acetaldehydes, the subsequent
      olefination and the stereospecific 2,3-sigmatropic rearrangement. 

PMID- 24305742
TI  - New insights into the structure and dynamics of actinomycetal community during
      manure composting.
AB  - Despite advancing knowledge about the functional role of actinomycetes in
      degrading lignocellulosic materials, definitive knowledge concerning the
      diversity and dynamics of the actinomycetal community in composting is still
      lacking. In this study, real-time polymerase chain reaction (PCR) coupled with
      denaturing gradient gel electrophoresis (DGGE) and clone library construction
      were applied to investigate actinomycetal diversity and dynamics in a pilot-scale
      composting. Quantitative real-time PCR data revealed that actinomycetes accounted
      for 18-86 % of bacteria and that the fraction peaked during the maturing phase,
      indicating that Actinobacteria were critical to the compost ecosystem.
      Qualitatively, actinomycetal communities displayed distinct temporal variations
      during composting. Fourteen distinct genera of actinomycetes and an unknown group
      were observed in manure composts. Redundancy analysis indicated that temperature
      exerted an influence over the actinomycetal communities. Specifically, pathogenic
      Corynebacterium species dominated in the initial phase, whereas the genera
      Saccharomonospora and Thermobifida were abundant in the thermophilic phase. In
      maturing composts, mesophilic Micrococcineae members were most prevalent. The
      dominant thermophiles along with Micrococcineae may jointly facilitate the
      degradation of lignocellulosic materials during composting. Together, our
      research revealed a more detailed ecological and potential functional role for
      actinomycetes in the compost ecology.

PMID- 24305744
TI  - Divacancies in diamond: a stepwise formation mechanism.
AB  - Diffusion of monovacancies in diamond creates various trapped multivacancy
      clusters. The simplest diffusion process leads to a divacancy, V2. The formation
      of V2 is a critical step in the formation of larger vacancy clusters. We explored
      the relaxed potential energy surfaces in the formation of V2 by ab initio density
      functional theory (DFT) obtaining structures, relative energies, diffusion
      barriers and reaction paths. The constricted environment of a diamond lattice
      leads to unexpected chemical bonding situations with unusually elongated carbon
      carbon bonds that have multicenter character. Divacancies separated by one carbon
      are not stable. Even though the divacancy is the most stable final product, a
      novel isolated divacancy with two vacant sites separated by two bonded carbons [V
      C=C-V] can be transformed into a divacancy only via a very large (>4.3 eV)
      barrier and therefore it should be a defect observable in irradiated diamonds.
      Trapping of a vacancy by another by forming a stable divacancy trap affects the
      development of NV-defects in nitrogen implanted diamonds that are subject to
      active current interest in a wide range of applications.

PMID- 24305745
TI  - Improving data resolution and statistical rigor in the analysis of bivalve shells
      as environmental archives.
AB  - Bivalves secrete their shells in an annual fashion, resulting in discrete bands
      of growth within each shell. In doing so, they may incorporate trace elements in
      concentrations reflecting exposure. This may make it possible to use them as
      archives of environmental information, such as contamination events. In this
      study, we used laser ablation inductively coupled plasma-mass spectrometry to
      analyze trace elements (Cd, Cu, Mn, Pb and Zn) on a fly-scanning transect
      perpendicular to the growth annuli of the freshwater bivalve Elliptio
      hopetonensis collected from the Altamaha river system. Concentrations of Mn from
      multiple shells at each site were correlated and average Mn data series were
      formed. Periodicity of Mn data was determined and sampling errors removed using
      an autoregression model. The Mn data series at each site were shown to have
      regular fluctuations of high and low concentrations. Fluctuations were similar
      between the shells from the same site but different between shells from different
      sites, demonstrating that Mn deposition in the shells of E. hopetonensis follows
      a regular, seasonal pattern but that growth differs between sites with different
      environments. Cd, Cu, Pb and Zn could not be analyzed in a statistically robust
      manner. This is the first study to attempt to improve data resolution by using
      the fly-scanning approach and, additionally, the first to apply an autoregression
      model to Mn data from bivalve annuli. Further study is required to develop this
      approach for environmental monitoring. 

PMID- 24305746
TI  - Heterotopic pregnancy following IVF-ET: successful treatment with salpingostomy
      under spinal anesthesia and continuation of intrauterine twin pregnancy.
AB  - The extended use of assisted reproductive technologies is increasing the
      heterotopic pregnancies, leading to a potentially dangerous condition for the
      intrauterine pregnancy and the mother. We report a case of unruptured heterotopic
      pregnancy following IVF-ET at 6 weeks of gestation and the patient was treated
      with salpingostomy under spinal anesthesia. The intrauterine twin pregnancy
      course was uneventful with the delivery of healthy babies at 34th week by
      Cesarean section. 

PMID- 24305747
TI  - Advanced utero-vaginal prolapse and vaginal vault suspension: synthetic mesh vs
      native tissue repair.
AB  - PURPOSE: To compare prosthetic and ligament vaginal vault suspension at vaginal
      hysterectomy in patients, with utero-vaginal stage III-IV pelvic organ prolapse
      quantification. METHODS: A retrospective case-control study was designed to
      compare 61 patients who had undergone Posterior intravaginal slingplasty (PIVS)
      with 61 patients in a matched control group who had undergone uterosacral
      ligament suspension (ULS). The primary outcome was to compare anatomic vaginal
      vault failure rate. The secondary outcomes were subjective cure and cure without
      adverse events. RESULTS: Follow-up mean duration for the PIVS and ULS groups was
      56.2 and 57.7 months, respectively. Recurrent vault prolapse was observed more
      frequently in the ULS group with pre-intervention stage IV prolapse (0 vs 14.8 %;
      p = 0.04), while there was no difference in prolapse recurrence at any vaginal
      site. Although the subjective cure of PIVS and ULS was superimposable (91.8 vs
      86.9 %; p = 0.25), there was a significantly higher cure rate, without adverse
      events, in the ULS group (90.2 vs 100 %; p = 0.01). CONCLUSIONS: Non-mesh vaginal
      vault repair should be considered the first-line measure at vaginal hysterectomy;
      prosthetic repair should be used for therapeutic purposes in patients with
      vaginal vault recurrence and considered at vaginal hysterectomy only in selected
      subjects with complete utero-vaginal eversion.

PMID- 24305748
TI  - Medical management of early pregnancy failure (EPF): a retrospective analysis of
      a combined protocol of mifepristone and misoprostol used in clinical practice.
AB  - PURPOSE: To evaluate the efficacy of a combined protocol of mifepristone and
      misoprostol in the management of early pregnancy failure (EPF) and the average
      time to expulsion of tissue and rate of side effects. METHODS: Retrospective
      chart review of all consecutive women treated with primary medical management for
      EPF at our institution from 2006 to 2012. RESULTS: 168 patients were included in
      the present study. The overall success rate, defined as the absence of the need
      for surgical intervention, was 61 % and did not differ by calendar year. There
      was no difference in success rate grouped by diagnosis [intrauterine
      embryonic/fetal demise (IUED/IUFD) vs. anembryonic gestation; p = 0.30] or
      gestational age (<9 or >=9 weeks; p = 0.48). The success rate varied
      significantly according to the required dose of misoprostol, <=800 or >800 MUg
      (68 vs. 50 %, p = 0.029). Of the possible predictive factors of success, only the
      dose of misoprostol required was a significant independent negative predictor.
      Mean and median time to tissue expulsion after the first dose of misoprostol were
      8.4 and 5.5 h, respectively. The incidence of side effects was low with no blood
      transfusions required. CONCLUSIONS: The success rate in this study is markedly
      below published data. This can possibly be attributed to retrospective study
      design, allowing for physician subjectivity and patients' wishes in the absence
      of strict study requirements. The protocol was well tolerated with a paucity of
      side effects. We make suggestions for enhancing success rates in the clinical
      setting by optimizing medication protocols, establishing precise treatment
      guidelines and training physicians in the accurate interpretation of treatment
      outcomes.

PMID- 24305749
TI  - The effects of antenatal corticosteroids therapy on very preterm infants after
      chorioamnionitis.
AB  - PURPOSE: To evaluate the effectiveness of antenatal corticosteroids (AC) therapy
      on outcomes of very low birthweight infants with histologic chorioamnionitis.
      METHODS: We performed a retrospective analysis of 10,935 single infants born at a
      gestational age between 22 + 0 and 33 + 6 weeks and birth weight <1,500 g.
      Clinical data were obtained from the Neonatal Research Network that included the
      tertiary neonatal intensive care units throughout Japan between 2003 and 2008.
      RESULTS: Data of 7,896 infants were available for the period 2003-2008 and were
      included in the analysis. According to logistic regression analysis, AC were
      significantly associated with reduced mortality [odds ratio (OR) = 0.50; p <
      0.001], lower incidence of respiratory distress syndrome (OR = 0.72; p < 0.001),
      neonatal seizure (OR = 0.65; p = 0.003) and intraventricular hemorrhage (OR =
      0.68; p = 0.001) in cases after histologic chorioamnionitis compared with the
      cases had no AC therapy (n = 3,271 vs. 4,625). Antenatal corticosteroids were
      significantly associated with reduced mortality [odds ratio (OR) = 0.60; p <
      0.001] among the cases without histologic chorioamnionitis. CONCLUSION: In the
      retrospective population-based study in Japan, AC exposure was significantly
      associated with a lower rate of death and neurological morbidity in cases with
      histologic chorioamnionitis. These outcome data in Japan will be important for
      further improvement of antenatal practice and care.

PMID- 24305750
TI  - Prevalence of cervical intraepithelial neoplasia (CIN) in patients attending
      Minia Maternity University Hospital.
AB  - BACKGROUND: Cervical cancer is the second most common cancer of the genital
      tract. Wide use of screening programs can help in prevention of cervical cancer.
      OBJECTIVE: To screen and evaluate the prevalence of cervical intraepithelial
      neoplasia (CIN) by visualization of the cervix after application of 5 % acetic
      acid (VIA) in Minia Maternity University Hospital. PATIENTS AND METHODS: The
      study included 3,600 women from outpatient clinics of Minia Maternity University
      Hospital. They were screened for cervical cancer with the use of visual
      inspection of the cervix after application of 5 % acetic acid (VIA). Positive
      cases were subjected to colposcopy after referral to the colposcopy unit in the
      same hospital. Colposcopy-guided biopsies were done for colposcopic positive
      patients. One hundred and twenty women with negative VIA as control were randomly
      examined with colposcopy to evaluate the effectiveness of the test used, and no
      cases experienced cervical lesion. RESULTS: The prevalence was 5.8 % for cervical
      lesions, 1.4 % for HPV infection alone, 3.3, 0.84 and 0.27 % for CIN I, CIN II
      and CIN III, respectively. The prevalence of CIN II or higher was 1.11 %
      (40/3,600). CONCLUSIONS: Prevalence of CIN in the study population was 138 out of
      1,800 cases (7.7 %). Pre-invasive high-grade lesions represent 1.3 % in
      participant women. VIA can be used in national programs for cervical cancer
      screening.

PMID- 24305751
TI  - Quantum replication at the Heisenberg limit.
AB  - No process in nature can perfectly clone an arbitrary quantum state. But is it
      possible to engineer processes that replicate quantum information with
      vanishingly small error? Here we demonstrate the possibility of probabilistic
      super-replication phenomena where N equally prepared quantum clocks are
      transformed into a much larger number of M nearly perfect replicas, with an error
      that rapidly vanishes whenever M is small compared with N(2). The quadratic
      replication rate is the ultimate limit imposed by quantum mechanics to the
      proliferation of information and is fundamentally linked with the Heisenberg
      limit of quantum metrology. 

PMID- 24305752
TI  - Small molecules: an overview of emerging therapeutic options in the treatment of
      psoriasis.
AB  - Psoriasis is a chronic condition which requires ongoing management with therapies
      that have demonstrated favorable safety and efficacy profiles in long-term use.
      While biologics changed the way psoriasis is treated by providing effective
      targeted therapy, they are not without limitations. However, small molecules are
      emerging therapeutic options for the treatment of psoriasis. Several oral and
      topical small molecules, spanning different therapeutic classes, are proving to
      be promising treatment options in psoriasis. While studies to date have yielded
      positive results, further investigation of these agents are warranted for both
      safety and efficacy. 

PMID- 24305753
TI  - Chronic urticaria and autoimmunity.
AB  - Chronic urticaria is defined as hives, typically occurring daily, for greater
      than 6 weeks duration. Chronic idiopathic urticaria, which has no discernable
      external cause, comprises the majority of cases of chronic urticaria. Over half
      of all cases of chronic idiopathic urticaria are thought to occur by an
      autoimmune mechanism, primarily autoantibodies against the high affinity
      immunoglobulin E (IgE) receptor (FcepsilonRI). Chronic urticaria is hypothesized
      to occur because of a predilection in the patient to develop reactions to self.
      Supporting this hypothesis, a strong association has been found between chronic
      urticaria and additional autoimmune diseases, such as thyroid disease, rheumatoid
      arthritis, systemic lupus erythematosus, Sjogren's syndrome, celiac disease and
      type 1 diabetes, among others. Herein, we review the associations between chronic
      urticaria, thyroid disease, and other autoimmune disorders, as well as the
      implications that these correlations hold for therapeutic intervention in chronic
      urticaria. 

PMID- 24305754
TI  - Clinicopathological characteristics and prognosis of mucinous breast carcinoma.
AB  - PURPOSE: The clinical features and prognosis of mucinous breast carcinoma (MBC)
      are unclear because of its rarity. The aim was to describe the
      clinicopathological features and prognosis of patients with MBC in comparison
      with nonmucinous breast carcinoma (NMBC). Furthermore, we described the
      biological behavior of pure mucinous breast carcinoma (PMBC) by comparing
      clinicopathological features and prognosis with mixed mucinous breast carcinoma
      (MMBC). METHODS: We reviewed the records of 5,872 consecutive patients diagnosed
      with breast carcinoma who were resected surgically from March 2003 to October
      2010. Among them, 117 patients with MBC were compared to 5,575 patients with
      NMBC. Furthermore, 88 patients with PMBC were compared to 29 patients with MMBC.
      RESULTS: There were statistical differences in age, pN stage, ER level, and PR
      level between the patients with MBC and NMBC. There were statistical differences
      in pT stage and pN stage between the patients with PMBC and MMBC. The overall
      five-year survival of patients with MBC was 88.1 % as compared with 81.9 % for
      patients with NMBC. The overall five-year survival of patients with PMBC was 91.3
      % as compared with 80.4 % for patients with MMBC. The overall five-year survival
      of patients with PMBC was 91.3 % as compared with 81.9 % for patients with NMBC.
      CONCLUSIONS: PMBC tended to have a better prognosis in comparison with other
      types of breast carcinoma.

PMID- 24305755
TI  - Adjuvant therapy in stage II thymic carcinoma.
AB  - PURPOSE: The aim of this study is to investigate the impact of chemotherapy
      and/or radiotherapy on disease-free survival and overall survival for patients
      with stage II thymic carcinoma. METHODS: We retrospectively evaluated the outcome
      of 31 patients with Masaoka stage II thymic carcinoma who were treated between
      1995 and 2009 in Zhejiang Cancer Hospital. Survival curves were plotted using the
      Kaplan-Meier method. The Cox proportional hazard model was used for multivariate
      analysis. RESULTS: Thirty-one patients were included in current study. The most
      common histological subtypes were squamous cell carcinoma (48.4 %), followed by
      undifferentiated carcinoma (19.4 %) and neuroendocrine tumor (19.4 %).The 5-year
      disease-free survival and overall survival rate was 74.6 and 89.5 %,
      respectively. Univariate and multivariate analysis revealed that radiotherapy
      and/or chemotherapy did not statistically associated with disease-free survival
      and overall survival. CONCLUSION: Our result indicated that adjuvant therapy
      after complete resection could not impact the disease-free survival and overall
      survival of patients with stage II thymic carcinoma.

PMID- 24305756
TI  - Control of charge transport in a semiconducting copolymer by solvent-induced long
      range order.
AB  - Recent reports on high-mobility organic field-effect transistors (FETs) based on
      donor-acceptor semiconducting co-polymers have indicated an apparently strong
      deviation from the paradigm, valid for a series of semi-crystalline polymers,
      which has been strictly correlating charges mobility to crystalline order. This
      poses a severe limit on the control of mobility and a fundamental question on the
      critical length scale which is dominating charge transport. Here we focus on a
      well-known model material for electron transport, a naphthalene-diimide based
      copolymer, and we demonstrate that mobility can be controlled over two orders of
      magnitude, with maximum saturation mobility exceeding 1 cm(2)/Vs at high gate
      voltages, by controlling the extent of orientational domains through a deposition
      process as simple as spin-coating. High mobility values can be achieved by
      adopting solvents inducing a higher amount of pre-aggregates in the solution,
      which through the interaction with the substrate, provide the polymer with liquid
      crystalline like ordering properties.

PMID- 24305757
TI  - An infant with atrophic and wrinkled abdominal skin.

PMID- 24305758
TI  - Isolation and culture of cereal protoplasts : Part 2: Embryogenesis and plantlet
      formation from protoplasts of Pennisetum americanum.
AB  - Protoplasts isolated from embryogenic suspension cultures derived from immature
      embryos of pearl millet (Pennisetum americanum) gave rise to cell masses. These
      cell masses upon transfer to a hormone-free medium formed embryoids, which
      further developed into plantlets with roots and shoots. 

PMID- 24305759
TI  - Chromosomal variability in tissue cultures and regenerated plants of Hordeum.
AB  - Spontaneous polyploidy, aneuploidy, and chromosomal rearrangements were observed
      in callus and suspension cultures of Hordeum vulgare, H. jubatum, and their
      interspecific hybrid. The extent to which each class of chromosomal variability
      was present in a culture depended upon differentiated state, age, and history.
      Cytological and isozymic analysis of subdivided callus cultures revealed spatial
      segregation of chromosomal variability. Cytogenetic analyses were performed to
      determine the expression of this in vitro chromosomal variability in
      corresponding regenerated plant tissues. A complete loss of polyploidy and a
      decrease in aneuploidy and chromosomal rearrangements were observed. Analyses of
      specific isozyme activities in regenerates suggested that a quantitative
      segregation of H. vulgare and H. jubatum genomes had occurred in tissue cultures
      of their interspecific hybrid. Possible uses of in vitro chromosomal variability
      for plant breeding and genetical studies are discussed. 

PMID- 24305760
TI  - Correlation between chiasma frequency and quantitative traits in upland cotton
      (Gossypium hirsutum L.).
AB  - Four locally adapted and high yielding cultivars of upland cotton were examined
      in order to elucidate the relationship between total chiasma frequency and
      quantitative traits, including yield and fiber properties. Total chiasma
      frequency per nucleus was found to correlate positively with boll number (r =
      0.4041), seed cotton yield (r = 0.6003), seed index (r = 0.4624), lint yield (r =
      0.7325), and lint index (r = 0.9534). The data are discussed from the point of
      view that the heterozygosity caused by increased chiasma frequency in inbreeding
      cotton cultivars is an important compensating mechanism for enhancing effective
      recombination and genetic variability. 

PMID- 24305761
TI  - Random and fixed effects in plant genetics.
AB  - A general model for any type of genetic entry is developed which takes into
      account both the factorial model of gene effects and the ancestral sources,
      whether inbred lines or outbred varieties, of the genes.Utilizing the model,
      various genetic designs of fixed entries are explored for the estimation of
      genetic effects and the testing of genetic hypotheses. These designs consisted of
      generation means - parents, crosses, various types of backcrosses, and so on -
      stemming from one or more pairs of parents, and of hybrid combinations from
      factorial mating designs. Limitations, from the standpoint of genetic effects
      that can be estimated and genetic hypotheses that can be tested, are developed in
      considerable detail.When entries from the factorial mating designs are considered
      to be random, attention is focused on the estimation of genetic variances, rather
      than effects, and on the concomitant changes in the tests of genetic hypotheses.
      While there is considerable improvement over fixed entries in the number of types
      of genetic variances that can be estimated, and of genetic hypotheses that can be
      tested, they are still very limited in contrast to what would be most desirable. 

PMID- 24305762
TI  - Effect of autopolyploidy on quantity and quality of protein in barley.
AB  - The range and mean protein content of autotetraploids of high-lysine Notch-2
      mutants of barley were consistently higher than the diploids in C3 and C4
      generations of colchicine treated seeds. Amino acid analysis of whole grain meal
      of diploid Notch-2 and one strain of its autotetraploid revealed differences in
      the amino acid composition. The proportion of albumin in the diploid and the
      autotetraploid Notch-2 was higher by 21% and 45% respectively, in comparison to
      the parent 'N.P. 113', whereas the glutelin fraction was significantly higher in
      the autotetraploid. The autotetraploid, with increased glutelin and decreased
      prolamin, showed no increase in lysine. It is possible that the recessive high
      lysine gene may be lacking dosage effect, resulting in no increase in lysine in
      the autotetraploid, whereas protein content, a polygenically controlled trait, is
      enhanced due to genome duplication. 

PMID- 24305763
TI  - Spontaneous chlorophyll mutants of Pennisetum americanum: Genetics and
      chlorophyll quantities.
AB  - Thirteen spontaneously occurring chlorophyll deficient phenotypes have been
      described and their genetic basis was established. Ten of these - 'white', 'white
      tipped green', 'patchy white', 'white virescent', 'white striping 1', 'white
      striping 2', 'white striping 4', 'fine striping', 'chlorina' and 'yellow
      virescent' showed monogenic recessive inheritance and the remaining three -
      'yellow striping', 'yellow green' and 'light green' seedling phenotypes showed
      digenic recessive inheritance. The genes for (i) 'white tipped green' (wr) and
      'yellow virescent' (yv) and (ii) 'patchy white' (pw) and 'white striping 1' (wst
      1) showed independent assortment. Further, the genes for 'white' (w), 'white
      tipped green' (wr) and 'yellow virescent' (yv) were inherited independently of
      the gene for hairy leaf margin (Hm).In the mutants - 'white tipped green',
      'patchy white', 'white striping 1', 'white striping 2', 'fine striping',
      'chlorina', 'yellow virescent', 'yellow striping', 'yellow green' and 'light
      green' phenotypes total quantity of chlorophyll was significantly less than that
      in the corresponding controls, while in 'white virescent' there was no reduction
      in the mature stage. For nine of the mutants the quantity of chlorophyll was also
      estimated in F1's (mutant x control green). In F1's of six of the mutants -
      'white tip', 'patchy white', 'chlorina', 'yellow virescent', 'fine striping' and
      'yellow striping' the quantity of chlorophyll was almost equal to the wild type.
      In the F1's of three of the mutants - 'white striping 1', 'white striping 2' and
      'light green' an intermediate value between the mutant and wild types was
      observed. In 'yellow virescent' retarded synthesis of chlorophyll, particularly
      chlorophyll a was observed in the juvenile stage. Reduced quantity of chlorophyll
      was associated with defective chloroplasts. In the mutants - 'white tipped green,
      'white virescent', 'fine striping', 'chlorina', 'yellow striping', 'yellow green'
      and 'light green' defective plastids were also observed. In 'patchy white'
      secondary destruction of chlorophylls and the presence of defective plastids were
      found to be associated with reduced chlorophyll quantity at maturity.Paper
      chromatographic studies of leaf flavonoids revealed some variation between the
      inbreds, but there were three common spots, 7, 8 and 9, except for PDP in which
      the spot 8 was absent. Chlorophyll deficient mutants differed from their
      respective controls in the absence of one or more of the spots present in the
      controls and in the presence of new spots in some of the mutants.Most of the
      chlorophyll mutants showed higher survival rate in the Kharif season than in Rabi
      season which was attributed to the higher mean day temperature and longer day
      light period in the Kharif season than in Rabi season. 

PMID- 24305764
TI  - Tailoring of quantum dot emission efficiency by localized surface plasmon
      polaritons in self-organized mesoscopic rings.
AB  - We report on the tailoring of quantum dot (QD) emission efficiency by localized
      surface plasmon polaritons in self-organized mesoscopic rings. Ag nanoparticles
      (NPs) with CdSe QDs embedded in a polymeric matrix are spatially organised in
      mesoscopic rings and coupled in a tuneable fashion by breath figure formation.
      The mean distance between NPs and QDs and consequently the intensity of QD
      photoluminescence, which is enhanced by the coupling of surface plasmons and
      excitons, are tuned by acting on the NP concentration. 

PMID- 24305765
TI  - Psychosocial impact of cancer.
AB  - Diagnosis and treatment of malignant diseases affect in many ways the lives of
      patients, relatives and friends. In this chapter, we summarise the current
      knowledge concerning the psychosocial consequences of cancer. 

PMID- 24305766
TI  - Fear of progression.
AB  - Fear of progression (or fear of recurrence) is an appropriate, rational response
      to the real threat of cancer and cancer treatments. However, elevated levels of
      fear of progression can become dysfunctional, affecting well-being, quality of
      life, and social functioning. Research has shown that fear of progression is one
      of the most frequent distress symptoms of patients with cancer and with other
      chronic diseases. As a clear consensus concerning clinically relevant states of
      fear of progression is currently lacking, it is difficult to provide a valid
      estimate of the rate of cancer patients who clearly suffer from fear of
      progression. However, recent systematic reviews suggest that probably 50 % of
      cancer patients experience moderate to severe fear of progression. Furthermore,
      many patients express unmet needs in dealing with the fear of cancer spreading.
      These results underline the necessity to provide effective psychological
      treatments for clinical levels of fear of progression. A few psychosocial
      interventions for treating fear of progression have been developed so far. Our
      own, targeted intervention study showed that dysfunctional fear of progression
      can be effectively treated with a brief group therapy.

PMID- 24305767
TI  - Gender opportunities in psychosocial oncology.
AB  - Avoidance of discussions of sex and gender in medicine reflects the larger
      lingering societal discomfort with any discussion that links potential sex and
      gender differences with superiority. The data show that there is more intra
      sexual then intersexual variation in men and women. When speaking about sex and
      gender the literature reflects that, on average, there are many differences, and
      although they are small, that when taken together, the impact may be quite
      robust. Sex and gender differences are relevant to how individuals, couples, and
      families experience and cope with serious illness; however, these important and
      obvious variables are seldom taken into account when counseling seriously ill
      patients and their families. Cancer is a complex disease that brings into sharp
      relief the potential alignments and misalignments in the sexes. In this chapter
      we have attempted to communicate the imperative for and importance of
      understanding people under stress within the context of sex and gender. Gender
      specific medicine is a very young movement for scientific study but one that has
      great potential to maximize adaptation and mutual respect at a time when men and
      women are redefining themselves and adapting to new social realities and
      challenges. 

PMID- 24305768
TI  - Psycho-oncology: a patient's view.
AB  - Culturally the most important, valued, and less stigmatized part of cancer care
      is the medical part: The surgeon cutting the tumors out and the oncologist
      leading the strategic decision-making of the medical treatments available. The
      least valued and stigmatized part of cancer remains the psychosocial care. This
      chapter describes--through the eyes of an academic, psychologist, stage IV
      melanoma patient, and patient advocate--how one patient navigated changing psycho
      oncological needs from early stage to stage IV through a whole range of
      psychological interventions available. Her voice joins that of all cancer
      patients around the world whom are urgently calling for psycho-oncological care
      to be fully recognized as a central part of cancer treatment. 

PMID- 24305769
TI  - The oncological patient in the palliative situation.
AB  - Palliative care approaches the patient and his or her suffering with a
      biopsychosocial-spiritual model. Thus, it is the strength of palliative care to
      complement the diagnosis driven approach of medical cancer care by a problem and
      resources-based assessment, participatory care plan, and patient-directed
      interventions. Interventions need to reflect timely prognosis, target population
      (the patient, the family carer, the professional), and level of trust and
      remaining energy. In palliative care the relevance of psycho-oncological aspects
      in the care of the terminally ill is considerable in the understanding of the
      overall suffering of patients approaching death and their loved ones and in their
      care and support. There is little evidence to date in terms of clinical benefit
      of specific psycho-oncological interventions in the last months or weeks of life,
      but there is evidence on effects of stress reduction and reduced anxiety if locus
      of control can stay within the patient as long as possible. One major difficulty
      in psychosocial research at the end-of-life, however, is defining patient
      relevant outcomes. 

PMID- 24305770
TI  - Psychosocial burden of family caregivers to adults with cancer.
AB  - A person living with cancer will potentially have some degree of physical,
      cognitive, and/or psychological impairment, periods of unemployment, financial
      concerns, social isolation, and existential questions, any or all of which can
      impact the family and friends who surround them. In our current era of
      healthcare, patients with cancer receive invasive diagnostic studies and
      aggressive treatment as outpatients, and then convalesce at home. As such, cancer
      family caregivers are essential partners with the healthcare team. The
      intricacies of the cancer family caregiver role and responsibilities are
      demanding and may lead to increased morbidity and mortality-in effect, the cancer
      family caregiver can become a second patient in need of care. This chapter
      discusses the psychosocial burden of family caregivers to adults with cancer, and
      includes information on caregiver mood disturbance and psychological impairment
      and some of the mutable factors that contribute to these states (i.e., sleep
      disturbance, decline in physical health, and restriction of activities),
      uncertainty, spiritual concerns, and caregiver witnessing. There is a discussion
      of the factors that influence the caregiving experience (caregiver
      characteristics, patient characteristics, and social supports). The chapter
      concludes with comments on the state of caregiver research. 

PMID- 24305771
TI  - Rehabilitation for cancer patients.
AB  - Rehabilitation for cancer patients aims at reducing the impact of disabling and
      limiting conditions resulting from cancer and its treatment in order to enable
      patients to regain social integration and participation. Given current trends in
      cancer incidence and survival along with progress in medical treatment, cancer
      rehabilitation is becoming increasingly important in contemporary healthcare.
      Although not without limitations, the International Classification of
      Functioning, Disability, and Health (ICF) provides a valuable perspective for
      cancer rehabilitation in understanding impairments in functioning and activity as
      the result of an interaction between a health condition and contextual factors.
      The structure of cancer rehabilitation varies across countries as a function of
      their health care systems and social security legislations, although there is a
      broad consensus with respect to its principal goals. Cancer rehabilitation
      requires a careful assessment of the individual patient's rehabilitation needs
      and a multidisciplinary team of health professionals. A variety of rehabilitation
      interventions exist, including psycho-oncological and psycho-educational
      approaches. Research on the effectiveness of cancer rehabilitation provides
      evidence of improvements in relevant outcome parameters, but faces some
      methodological challenges as well. 

PMID- 24305772
TI  - Cancer survivorship in adults.
AB  - With the favorable trend regarding survival of cancer in the Western world, there
      is an increasing focus among patients, clinicians, researchers, and politicians
      regarding cancer survivors' health and well-being. Their number is rapidly
      growing and more than 3 % of the adult populations in Western countries have
      survived cancer for 5 years or more. Cancer survivors are at increased risk for a
      variety of late effects after treatment, some life-threatening such as secondary
      cancer and cardiac diseases, others might negatively impact on their daily
      functioning and quality of life. The latter might include fatigue, anxiety
      disorders and difficulties returning to work while depression does not seem to be
      more common among survivors than in the general population. Still, the majority
      of survivors regain their health and social functioning. The field of cancer
      survivorship research has been rapidly growing. Models for follow-up care of
      cancer survivors have been proposed, but how to best integrate the knowledge of
      the field into clinical practice with adequate follow-up of cancer survivors at
      risk for developing late effects is still an unsolved question. 

PMID- 24305773
TI  - Psycho-oncological interventions and psychotherapy in the oncology setting.
AB  - A person who faces the diagnosis of cancer is subjected to changes within his
      body, but also with regard to his view of himself and his social relationships.
      Cancer-related psychological distress occurs frequently and has been reported to
      have different prevalence according to cancer type and stage of disease.
      Psychological disorders are known to be underdiagnosed and thus undertreated in
      the oncology setting, since clinicians might miss the symptoms of psychological
      distress, misinterpret them, or lack the time and resources to respond
      adequately. The main psychiatric disturbances observed in patients with cancer
      are adjustment disorders and affective disorders (anxiety and depression), which
      in the majority of patients are due to stressors related to the disease and pre
      existing psychological vulnerabilities; however, they might also be a direct
      consequence of biological causes either resulting from treatment side effects or
      from modifications induced by the cancer. This chapter aims to provide
      theoretical and practical information concerning psycho-oncological approaches,
      complemented by some reflexions on their clinical and scientific evidence,
      focussing essentially on verbal psychological interventions and especially on
      psychotherapy in patients with cancer. 

PMID- 24305774
TI  - Quality of life in oncology.
AB  - Continuous improvements in the diagnosis and treatment of cancer lead to improved
      cure rates and longer survival. However, in many patients, the disease becomes
      chronic. In this context, the patients' quality of life (QOL) becomes a crucial
      issue. After an introduction about QOL, results from different areas of cancer
      treatment are presented considering their impact on QOL. Finally, implications
      are discussed for researchers, clinicians, and patients. 

PMID- 24305775
TI  - Platelets in cancer and thrombosis.
AB  - Platelets are the smallest circulating blood cells and their major function is
      the maintenance of haemostasis. They do not have a nucleus, but instead a
      multitude of granules that contain molecules important for several physiological
      processes. These granules can be released after platelet activation and thereby
      platelets take part in haemostasis, wound repair or immunological processes.
      Furthermore, platelets are also involved in the pathophysiology of several
      diseases, including cancer. Platelets can support various steps of cancer
      development and progression by promoting tumour growth, angiogenesis and
      metastasis. Moreover, platelets contribute to the hypercoagulable state
      frequently observed in cancer patients, leading to an increased risk of venous
      thromboembolism (VTE). In previous studies a high platelet count was repeatedly
      found to be associated with an elevated risk of VTE and a worse prognosis in
      patients with cancer. The aim of this review is to give an overview of the most
      important alterations of platelet physiology in cancer patients and how these
      alterations may influence cancer disease and contribute to cancer-associated VTE.

PMID- 24305777
TI  - Autistic traits and abnormal sensory experiences in adults.
AB  - Sensory processing abnormalities are common in autism spectrum disorders (ASD),
      and now form part of the Diagnostic and Statistical Manual 5th Edition (DSM-5)
      diagnostic criteria, but it is unclear whether they characterize the 'broader
      phenotype' of the disorder. We recruited adults (n = 772) with and without an ASD
      and administered the Autism Quotient (AQ) along with the Adult/Adolescent Sensory
      Profile (AASP), the Cardiff Anomalous Perceptions Scale (CAPS), and the Glasgow
      Sensory Questionnaire (GSQ), all questionnaire measures of abnormal sensory
      responsivity. Autism traits were significantly correlated with scores on all
      three sensory scales (AQ/GSQ r = 0.478; AQ/AASP r = 0.344; AQ/CAPS r = 0.333; all
      p < 0.001). This relationship was linear across the whole range of AQ scores and
      was true both in those with, and without, an ASD diagnosis. It survived
      correction for anxiety trait scores, and other potential confounds such as mental
      illness and migraine. 

PMID- 24305776
TI  - Right temporoparietal gray matter predicts accuracy of social perception in the
      autism spectrum.
AB  - Individuals with an autism spectrum disorder (ASD) show hallmark deficits in
      social perception. These difficulties might also reflect fundamental deficits in
      integrating visual signals. We contrasted predictions of a social perception and
      a spatial-temporal integration deficit account. Participants with ASD and matched
      controls performed two tasks: the first required spatiotemporal integration of
      global motion signals without social meaning, the second required processing of
      socially relevant local motion. The ASD group only showed differences to controls
      in social motion evaluation. In addition, gray matter volume in the temporal
      parietal junction correlated positively with accuracy in social motion perception
      in the ASD group. Our findings suggest that social-perceptual difficulties in ASD
      cannot be reduced to deficits in spatial-temporal integration. 

PMID- 24305778
TI  - The effects of pectins on life span and stress resistance in Drosophila
      melanogaster.
AB  - The composition of diet is one of the major determining factors for lifespan. The
      dietary pectins are known to have anti-inflammatory properties and may influence
      aging and longevity. Here we demonstrate the lifespan-extending effect of the low
      methyl esterified (LM) commercial pectins CU701 and AU701 in wild-type strain of
      Drosophila melanogaster. The high methyl esterified (HM) pectin CU201 did not
      affect lifespan. LM pectin did not increase lifespan of males with a mutation in
      the Toll adaptor Myd88 gene and in both males and females with a mutation in the
      NF-kappaB ortholog Relish. LM pectin CU701 increased imagoes survival in stress
      conditions (oxidation, hyperthermia and starvation). However, the fertility of LM
      and HM pectins treated flies decreased. The treatment of the imagoes with LH and
      HM pectins induced the activation of whole-body expression of genes involved in
      DNA repair (D-GADD45, mei-9, spn-B), apoptosis (wrinkled/hid) and heat shock
      response (hsp70Aa). In contrast, the expression of proinflammatory PARP-1 gene
      decreased. In the intestines LH and HM pectins induced the mRNA expression of the
      NF-kappaB-dependent antimicrobial genes Defensin, Drosomycin and Metchnikowin.
      These results indicate that the observed lifespan-extending effect of the LM
      pectins may be mediated by intracellular pathways that involve NF-kappaB
      signalling and activation of stress resistance genes. 

PMID- 24305779
TI  - Oxidative stress decreases in the trophocytes and fat cells of worker honeybees
      during aging.
AB  - Trophocytes and fat cells of honeybees have been used for cellular senescence
      studies, but their oxidative stress and antioxidant enzyme activities with aging
      in workers is unknown. Here, we assayed reactive oxygen species and the
      activities of antioxidant enzymes in the trophocytes and fat cells of young and
      old workers. Young workers had higher reactive oxygen species levels, higher
      superoxide dismutase and thioredoxin reductase activities as well as lower
      catalase and glutathione peroxidase activities compared to old workers. Adding
      these results up, we propose that oxidative stress decreases with aging in the
      trophocytes and fat cells of workers. 

PMID- 24305780
TI  - How polar are choline chloride-based deep eutectic solvents?
AB  - Developing and characterizing green solvents with low toxicity and cost is one of
      the most important issues in chemistry. Deep Eutectic Solvents (DESs), in this
      regard, have shown tremendous promise. Compared to popular organic solvents, DESs
      possess negligible VOCs and are non-flammable. Compared to ionic liquids, which
      share many characteristics but are ionic compounds and not ionic mixtures, DESs
      are cheaper to make, much less toxic and mostly biodegradable. An estimate of the
      polarity associated with DESs is essential if they are to be used as green
      alternatives to common organic solvents in industries and academia. As no one
      physical parameter can satisfactorily represent solute-solvent interactions
      within a medium, polarity of DESs is assessed through solvatochromic optical
      spectroscopic responses of several UV-vis absorbance and molecular fluorescence
      probes. Information on the local microenvironment (i.e., the cybotactic region)
      that surrounds several solvatochromic probes [betaine dye, pyrene, pyrene-1
      carboxaldehyde, 1-anilino-8-naphthalene sulfonate (ANS), p-toluidinyl-6
      naphthalene sulfonate (TNS), 6-propionyl-2-(dimethylaminonaphthalene) (PRODAN),
      coumarin-153, and Nile Red] for four common and popular DESs formed from choline
      chloride combined with 1,2-ethanediol, glycerol, urea, and malonic acid,
      respectively, in 1 : 2 molar ratios termed ethaline, glyceline, reline, and
      maline is obtained and used to assess the effective polarity afforded by each of
      these DESs. The four DESs as indicated by these probe responses are found to be
      fairly dipolar in nature. Absorbance probe betaine dye and fluorescence probes
      ANS, TNS, PRODAN, coumarin-153, and Nile Red, whose solvatochromic responses are
      based on photoinduced charge-transfer, imply ethaline and glyceline, DESs formed
      using alcohol-based H-bond donors, to be relatively more dipolar in nature as
      compared to reline and maline. The pyrene polarity scale, which is based on
      polarity-induced changes in vibronic bands, indicates reline, the DES composed of
      urea as the hydrogen bond donor, to be significantly more dipolar than the other
      three DESs. Response of pyrene-1-carboxaldehyde, a polarity probe based on
      inversion of n-pi* and pi-pi* states, hints at maline to be the most dipolar of
      the four DESs. The molecular structure of the H-bond donor in a DES clearly
      controls the dipolarity afforded by the DES. H-bonding and other specific solute
      solvent interactions are found to play an important role in solvatochromic probe
      behavior for the four DESs. The cybotactic region of a probe dissolved in a DES
      affords information on the polarity of the DES towards solutes of similar nature
      and functionality. 

PMID- 24305781
TI  - Hearing threshold estimation by auditory steady-state responses with narrow-band
      chirps and adaptive stimulus patterns: implementation in clinical routine.
AB  - Objective hearing threshold estimation by auditory steady-state responses (ASSR)
      can be accelerated by the use of narrow-band chirps and adaptive stimulus
      patterns. This modification has been examined in only a few clinical studies. In
      this study, clinical data is validated and extended, and the applicability of the
      method in audiological diagnostics routine is examined. In 60 patients (normal
      hearing and hearing impaired), ASSR and pure tone audiometry (PTA) thresholds
      were compared. ASSR were evoked by binaural multi-frequent narrow-band chirps
      with adaptive stimulus patterns. The precision and required testing time for
      hearing threshold estimation were determined. The average differences between
      ASSR and PTA thresholds were 18, 12, 17 and 19 dB for normal hearing (PTA <= 20
      dB) and 5, 9, 9 and 11 dB for hearing impaired (PTA > 20 dB) at the frequencies
      of 500, 1,000, 2,000 and 4,000 Hz, respectively, and the differences were
      significant in all frequencies with the exception of 1 kHz. Correlation
      coefficients between ASSR and PTA thresholds were 0.36, 0.47, 0.54 and 0.51 for
      normal hearing and 0.73, 0.74, 0.72 and 0.71 for hearing impaired at 500, 1,000,
      2,000 and 4,000 Hz, respectively. Mean ASSR testing time was 33 +/- 8 min. In
      conclusion, auditory steady-state responses with narrow-band-chirps and adaptive
      stimulus patterns is an efficient method for objective frequency-specific hearing
      threshold estimation. Precision of threshold estimation is most limited for
      slighter hearing loss at 500 Hz. The required testing time is acceptable for the
      application in everyday clinical routine.

PMID- 24305782
TI  - Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients
      with chronic tonsillitis.
AB  - To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has
      important roles in the differentiation of lymphoid cells, and oxidative stress in
      patients with chronic tonsillitis. Serum and tissue samples were obtained from 25
      patients who underwent tonsillectomy due to recurrent episodes of acute
      tonsillitis. In the control group, which also had 25 subjects, only serum samples
      were taken as obtaining tissue samples would not have been ethically appropriate.
      ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO)
      and malondialdehyde (MDA) were measured in the serum and tissue samples of
      patients and control group subjects. The serum values of both groups were
      compared. In addition, the tissue and serum values of patients were compared.
      Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group
      were significantly higher than those of the control group (p < 0.001), the
      antioxidant enzymes CA and CAT values of the patient group were significantly
      lower than those of the control group (p < 0.001). In addition, while CA, CAT and
      NO enzyme levels were found to be significantly higher in the tonsil tissue of
      the patient group when compared to serum levels (p < 0.05), there was no
      difference between tissue and serum MDA and ADA activity (p > 0.05). Elevated ADA
      activity may be effective in the pathogenesis of chronic tonsillitis both by
      impairing tissue structure and contributing to SOR formation. 

PMID- 24305783
TI  - Network analysis reveals functional cross-links between disease and inflammation
      genes.
AB  - Connections between inflammation and diseases are suggested important in
      understanding the genetic mechanisms of diseases. However, studies on the
      functional cross-links between inflammation and disease genes are still in their
      early stages. We integrated the protein-protein interaction (PPI), inflammation
      genes, and gene-disease associations to construct a disease-inflammation network
      (DIN). We found that nodes, which are both inflammation and disease genes (namely
      inter-genes), are topologically important in the DIN structure. Via mapping inter
      genes to PPI, we classified diseases into two categories, which are significantly
      different in Intimacy measuring the contribution of inflammation genes to the
      connections between disease pairs. Furthermore, we constructed a cross-talking
      subpathways network. As indicated, the cross-subpathway analysis shows great
      performance in capturing higher-level relationship among inflammation and disease
      processes. Collectively, The network-based analysis provides us a rather
      promising insight into the intricate relationship between inflammation and
      disease genes. 

PMID- 24305785
TI  - Mechanical behaviour of low-cost dynamic compression plates correlates with
      manufacturing quality standards.
AB  - PURPOSE: This study compares the mechanical properties of low-cost stainless
      steel dynamic compression plates (DCPs) from developing-world manufacturers,
      adhering to varying manufacturing quality standards, with those of high-cost DCPs
      manufactured for use in the developed world. METHODS: Standard-design ten-hole
      DCPs from six developing-world manufacturers and high-cost DCPs from two
      manufacturers in the developed world were studied. Nine plates from each
      manufacturer underwent mechanical testing: six in four-point monotonic bending to
      assess strength and stiffness and three in four-point bending fatigue.
      Statistical comparisons of the group means of monotonic bending test data were
      made, and a qualitative comparison was performed to assess failures in fatigue.
      RESULTS: Low-cost DCPs from manufacturers with at least one manufacturing quality
      standard had significantly higher bending strength and fewer failures in fatigue
      than did those from low-cost manufacturers with no recognised quality standards.
      High-cost DCPs demonstrated greater bending strength than did those in both low
      cost groups. There were no differences in stiffness and fatigue failure between
      high-cost DCPs and those low-cost DCPs with quality standards. However, high-cost
      DCPs were significantly less stiff and had fewer fatigue failures than low-cost
      DCPs manufactured without such standards. CONCLUSION: Significant differences
      were found in the mechanical properties of ten-hole DCP plates from selected
      manufacturers in the developing and developed worlds. These differences
      correlated with reported quality certification in the manufacturing process.
      Mechanical analysis of low-cost implants may provide information useful in
      determining which manufacturers produce implants with the best potential for
      benefit relative to cost.

PMID- 24305786
TI  - Limb versus life: the outcomes of osteosarcoma in Cambodia.
AB  - PURPOSE: Osteosarcoma (OS) is a serious disease affecting mainly children and
      young adults. In a resource poor setting the treatment options are limited and
      further obstacles can be found with respect to late presenting pathology, access
      to modern treatment modalities such as effective chemotherapy, and cultural
      reluctance to undergo certain treatments. Clinical outcome studies and
      epidemiology for this disease in developing countries are scarce. METHODS: We
      report on the outcomes of 30 patients treated by the CSC, a rehabilitative
      surgery centre in Cambodia, from 2002 to present. Enneking staging, location, and
      treatment protocols were evaluated. Outcome measures were months of survival,
      EDQ5S life quality scores and clinically relevant inquiries. Kaplan-Meier
      analysis estimates and the Wilcoxon chi-square test were used for statistical
      inferences. RESULTS: We find a grim prognosis for patients diagnosed with OS in
      Cambodia, 53% survive the first year after presentation and the five-year
      survival stands at 8%. There is a higher mean age for presentation of OS compared
      to Western norms, namely, 18.8 years and 21.7 years for females and males,
      respectively. CONCLUSIONS: Most patients opted for surgical treatment without
      adjuvant chemotherapy, which is not within the means of many Cambodian patients.
      Acceptance of amputation, earlier diagnosis, patient education, and access to
      standardized chemotherapy needs to be enhanced if Cambodian patients are to have
      a fighting chance.

PMID- 24305787
TI  - Bergapten prevents lipopolysaccharide mediated osteoclast formation, bone
      resorption and osteoclast survival.
AB  - PURPOSE: This study was designed to investigate the potential effect of bergapten
      on lipopolysaccharide (LPS)-mediated osteoclast formation, bone resorption and
      osteoclast survival in vitro. METHODS: After osteoclast precursor RAW264.7 cells
      were treated with bergapten (5, 20, 40 MUmol/L) for 72 hours in the presence of
      LPS (100 ng/ml), osteoclastogenesis was identified by tartrate-resistant acid
      phosphatase (TRAP) staining, and the number of TRAP-positive multinucleated cells
      [TRAP(+)MNCs] per well were counted. To investigate the effect of bergapten on
      osteoclastic bone resorption, RAW264.7 cells were treated with bergapten for six
      days in the presence of LPS, and the area of bone resorption was analyzed with
      Image Pro-Plus. Next, we examined apoptosis of RAW264.7 cells after bergapten
      incubation for 48 hours by flow cytometer using annexin V/propidium iodide (PI)
      double labeling. Finally, osteoclast survival was observed by Hoechst 33342
      labeling and Western blotting after bergapten treatment for 24 hours. RESULTS:
      Data showed that bergapten (5-40 MUmol/L) dose-dependently inhibited LPS-induced
      osteoclast formation and bone resorption. Treatment with bergapten triggered
      apoptotic death of osteoclast precursor RAW264.7 cells in a dose-dependent
      manner. Furthermore, bergapten significantly reduced the survival of mature
      osteoclast, as demonstrated by emergence of apoptotic nuclei and activation of
      apoptotic protein caspase 3/9. CONCLUSIONS: These findings suggest that bergapten
      effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival
      via apoptotic response of osteoclasts and their precursors. The study identifies
      bergapten as an inhibitor of osteoclast formation and bone resorption and
      provides evidence that bergapten might be beneficial as an alternative for
      prevention and treatment of inflammatory bone loss.

PMID- 24305788
TI  - Pre-operative autologous blood donation versus no blood donation in total knee
      arthroplasty: a prospective randomised trial.
AB  - PURPOSE: During total knee arthroplasty (TKA) blood loss can be significant and
      in spite of all techniques for reducing blood loss there is still a significant
      possibility for blood transfusions. For blood loss management during TKA, pre
      operative autologous blood donation (PABD) is still a standard of care. In this
      prospective randomised study we have evaluated the efficacy of PABD in patients
      undergoing TKA to answer the question whether there is any need for autologous
      blood donations during TKA and, if yes, for which group of patients. METHODS:
      Patients were randomised to three groups. In group 1 patients did not donate
      autologous blood, in group 2 patients donated 1 dose 72 hours prior to TKA and in
      group 3 patients donated autologous blood 14 days prior to TKA. In all patients
      haemoglobin, haematocrit, thrombocyte and reticulocyte values, iron
      concentrations (Fe, unsaturated iron binding capacity, total iron binding
      capacity), activated partial thromboplastin time, prothrombin time, and intra
      operative and post-operative blood loss were measured and compared. RESULTS: With
      PABD there was no reduction in allogeneic blood transfusions and a large number
      of taken doses of autologous blood was discarded, which significantly increased
      the cost of treatment for these patients. For patients undergoing TKA, PABD can
      provoke iatrogenic anaemia and thereby increase the likelihood of the need for
      allogeneic blood transfusion. CONCLUSIONS: Results of our study showed that PABD
      in non-anaemic patients is not justified and is not economically feasible.

PMID- 24305789
TI  - How to deal with lost to follow-up in total knee arthroplasty : a new method
      based on the competing risks approach.
AB  - PURPOSE: The aim of this study was to develop a more accurate method to deal with
      patients lost to follow-up based on the competing risks approach. METHODS: A
      cohort of 112 patients who received 143 primary cemented total knee
      arthroplasties forms the basis for this study. Follow-up was up to 25 years. The
      new method for dealing with lost to follow-up accounts for competing events (i.e.
      death and failure of a prosthesis) using the cumulative incidence estimator and
      estimates time to event for patients lost to follow-up using national demographic
      registries. The results of this new method were compared with the worst case
      scenario estimated by Kaplan-Meier. RESULTS: Six different situations were
      identified covering all possible situations in long-term follow-up for total knee
      arthroplasty. The new method--considering all patients lost to follow-up as
      revised--showed a twofold reduction in revision rate compared to the traditional
      worst case scenario using Kaplan-Meier. CONCLUSIONS: Lost to follow-up should be
      prevented whenever possible, but this may be unavoidable for long-term follow-up
      studies. In situations where lost to follow-up does occur, the new proposed
      method offers an efficient and valid approach to deal with this problem.

PMID- 24305784
TI  - The emergence of the mitochondrial genome as a partial regulator of nuclear
      function is providing new insights into the genetic mechanisms underlying age
      related complex disease.
AB  - Mitochondrial malfunction appears to be intimately associated with age and age
      related complex disorders but the precise pathological relevance of such
      malfunction remains unclear. Mitochondrial, and more specifically bioenergetic,
      malfunction is commonly encountered in cancer, degenerative disorders and aging.
      The identification of a mitochondrial-nuclear retrograde signaling pathway in
      yeast has facilitated the study of the corresponding retrograde signaling
      mechanisms induced in response to mitochondrial malfunction in mammals including
      human. Mitochondrial-nuclear crosstalk is critical for the maintenance of
      cellular homeostasis, and some mitochondrial DNA mutations may perturb crosstalk
      signaling. However, ascertaining whether mitochondrial malfunction is a cause or
      a consequence of disease development will be key to determining whether or not
      impaired crosstalk signaling is of direct pathological and hence therapeutic
      relevance. Here, we review what is known about the nuclear adaptive compensatory
      mechanisms induced in response to mitochondrial malfunction. We discuss the role
      of mitochondrial DNA variants in modulating the penetrance of human inherited
      disease caused by mutations in the nuclear genome and explore the underlying
      mechanisms by which they influence the retrograde response. We conclude that
      mitochondrial DNA variants have the potential to induce molecular signals through
      the mitochondrial-nuclear crosstalk mechanism, thereby promoting nuclear
      compensation in response to mitochondrial malfunction. The implications for the
      development of genetic or pharmaceutical interventions for the treatment of
      mitochondrial malfunction in complex disease are also explored. 

PMID- 24305790
TI  - The functional outcome of forty-nine single-incision suture anchor repairs for
      distal biceps tendon ruptures at the elbow.
AB  - PURPOSE: The objective of this retrospective study was to evaluate the functional
      results of distal biceps tendon repair using suture anchors via a single-incision
      approach. METHODS: Forty-nine patients were re-examined at a mean follow-up of
      44.2 +/- 32.1 months (range, 12-119 months). Subjective and objective criteria
      included patient's satisfaction, active range of motion (ROM), maximum isometric
      strength in flexion (at 45 degrees  and 90 degrees ), and supination of both
      arms. Functional scoring included the Morrey elbow score (MES) and the QuickDASH.
      Furthermore, follow-up radiographs were performed. RESULTS: Eighty-six percent of
      patients were highly satisfied or satisfied with their outcome. Compared to
      contralateral, the active ROM of elbow flexion, extension, and pronation was not
      affected; however, supination was decreased by 3 degrees  (P < 0.001). The
      isometric maximum strengths showed significant deficits in all tested scenarios
      (at 45 degrees , P = 0.002; at 90 degrees , P < 0.001; for supination, P <
      0.001). The MES and the QuickDASH were 97.2 +/- 4.9 and 7.9 +/- 13.9,
      respectively. Heterotopic ossifications (HO) were found in 39% of patients;
      however, with respect to scores and strength, no significant differences were
      seen compared to patients without HO. Moreover, four anchor failures were
      detected. CONCLUSIONS: Single-incision suture anchor repair provides high
      patient's satisfaction and good results with respect to ROM and functional
      scoring. Nevertheless, based on presented data, the patient has to be informed of
      postoperative HO and especially for supination strength weakness after surgery.
      Distal biceps tendon repair should be reserved for experienced upper extremity
      surgeons to avoid procedure-related complications.

PMID- 24305791
TI  - Computer-assisted unicompartmental knee arthroplasty using dedicated software
      versus a conventional technique.
AB  - PURPOSE: The aim of this study was to retrospectively compare the results of two
      matched-paired groups of patients who had undergone a medial unicompartmental
      knee arthroplasty (UKA) performed using either a conventional or a non-image
      guided navigation technique specifically designed for unicompartmental prosthesis
      implantation. METHODS: Thirty-one patients with isolated medial-compartment knee
      arthritis who underwent an isolated navigated UKA were included in the study
      (group A) and matched with patients who had undergone a conventional medial UKA
      (group B). The same inclusion criteria were used for both groups. At a minimum of
      six months, all patients were clinically assessed using the Knee Society Score
      (KSS) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) index.
      Radiographically, the frontal-femoral-component angle, the frontal-tibial
      component angle, the hip-knee-ankle angle and the sagittal orientation of
      components (slopes) were evaluated. Complications related to the implantation
      technique, length of hospital stay and surgical time were compared. RESULTS: At
      the latest follow-up, no statistically significant differences were seen in the
      KSS, function scores and WOMAC index between groups. Patients in group B had a
      statistically significant shorter mean surgical time. Tibial coronal and sagittal
      alignments were statistically better in the navigated group, with five cases of
      outliers in the conventional alignment technique group. Postoperative mechanical
      axis was statistically better aligned in the navigated group, with two cases of
      overcorrection from varus to valgus in group B. No differences in length of
      hospital stay or complications related to implantation technique were seen
      between groups. CONCLUSION: This study shows that a specifically designed UKA
      dedicated navigation system results in better implant alignment in UKA surgery.
      Whether this improved alignment results in better clinical results in the long
      term has yet to be proven.

PMID- 24305792
TI  - Progeny analysis of the interspecific somatic hybrids: Nicotiana tabacum (CMS) +
      Nicotiana sylvestris with respect to nuclear and chloroplast markers.
AB  - The progeny of a fusion experiment involving N. sylvestris protoplasts and X
      irradiated protoplasts of the cytoplasmic male sterile 'Line 92' (N. tabacum
      nucleus and alien, male-sterility inducing, cytoplasm) were analyzed. Three
      groups of somatic hybrid plants resulted: Type A, Type B-1 and Type B-2. These as
      well as their androgenic progenies and the progenies resulting from their
      pollination with N. tabacum or N. sylvestris were followed with respect to
      several nuclear and cytoplasmic traits. Those controlled by the nuclear genome
      were plant and flower morphologies; those controlled by genetic information in
      the cytoplasm were tentoxin sensitivity (affecting the coupling factor of
      chloroplast ATPase), the large subunit of ribulose bisphosphate carboxylase and
      the restriction endonuclease pattern of plastid DNA. A further cytoplasmic trait
      investigated (exact site of genetic control not known) was male sterility. The
      examinations of the somatic-hybrid groups and their respective progenies
      indicated that: Type A plants have N. sylvestris nuclei and 'Line 92' plastids;
      Type B-1 plants also have 'Line 92' plastids but their genome is composed of N.
      sylvestris and N. tabacum nuclei; Type B-2 plants with impaired male fertility
      had N. sylvestris plastids and N. sylvestris nuclei. 

PMID- 24305793
TI  - General resistance to late blight of Solanum tuberosum plants regenerated from
      callus resistant to culture filtrates of Phytophthora infestans.
AB  - Resistance of potato leaflets to culture filtrates of Phytophthora infestans is
      correlated with lower growth of the congenial parasite but not with lower
      sporulation. 

PMID- 24305794
TI  - New cytoplasmic male sterility sources in common wheat: Their genetical and
      breeding considerations.
AB  - Nuclei from Triticum aestivum L. cultivars 'Penjamo 62' and 'Siete Cerros 66'
      were introduced into the cytoplasms of different species of Aegilops and some
      subspecies (varieties) of T. dicoccoides by backcrossing. The sterile alloplasmic
      lines obtained were compared with the normal cultivars used as the recurrent
      pollen parents. According to the cytoplasmic effect, these cytoplasms were
      subdivided into three main groups. The first group possesses C(u) type cytoplasm,
      the second one possesses M type and the third group includes S, C and G type.
      Promising male sterile cytoplasms for hybrid wheat production were found in Ae.
      mutica, Ae. triuncialis and T. dicoccoides var. 'spontaneovillosum'. Based on
      these results and other information some conjectures were made concerning hybrid
      wheat breeding and phylogenetic differentiations of the cytoplasm. 

PMID- 24305795
TI  - Spontaneous interchanges in females of Drosophila melanogaster : Part 1:
      formation of half-translocations in XX and XXY females.
AB  - Herein is described an attempts to establish chromosome pairing-interchange
      relationships in Drosophila melanogaster female. For this purpose, the formation
      of half-translocations was studied in XXY and XX females bearing compounds of the
      second pair of autosomes. With respect to XXY females, it was expected that the
      free Y chromosome would pair with these compounds and that half-translocations
      involving 2L would arise. In as much as compound chromosomes in XX females had no
      partner for pairing, the formation of half-translocations involving 2L was not
      expected.Half-translocations were registered in the F1 from crosses of XX and XXY
      females to b j pr cn/T(Y;2)C males. The cross was designed to permit the
      detection of very rarely occurring non-homologue interchanges.Offspring number
      was 335 in XX females and 550 in XXY females. The majority of offspring consisted
      of individuals arisen from the spontaneous restitution of compounds and the
      formation of 2n egg cells. Based on phenotype, the offspring of XX females
      contained 4 individuals with half-translocations involving 2L; there were 48 such
      flies among the offspring of XXY females. As confirmed by progeny analysis, 38
      half-translocations occurred in XXY females and none in XX females. Of the 31
      spontaneous interchanges in XXY females 28 were recorded between the Y and the
      left compound, one between the Y and the right compound, and one between the X
      and the left compound. Non-homologue interchanges were of oogonial origin judging
      by the fact that individuals with half-translocations arose in clusters. Unlike Y
      - left compound interchanges, the interchanges between autosomal compounds seem
      to be of meiotic origin. 

PMID- 24305796
TI  - Ploidy and strain differences in seed germination of Glycine wightii at different
      pH levels.
AB  - Seeds from 27 wild strains (18 tetraploids and 9 diploids) of Glycine weightii
      were germinated at a pH range of 5 to 8. The differences in germination (%)
      between all the strains were highly significant but between pH levels they were
      only nearly significant (P=0.067) with no interaction between pH levels and
      strains. Mean germination (%) for all tetraploids seems to be slightly higher (?
      2%) than that for all diploids, especially at pH's 5, 7 and 8 but this may be due
      to the significantly longer time (? one day) it took tetraploids to complete
      germination. The apparent inverse relationship between seed weight and
      germination (%) was not significant.Mean germination time was highly significant
      for strains, pH's and their interaction. Increasing mean germination (%) resulted
      in decreasing mean germination time among strains. Large seeds took less time to
      germinate especially those from some of the tetraploid strains. This indicates
      that it is possible to produce a variety with high germination (%), fast
      germination rate and possibly large seeds. If the marked difference in pH
      tolerance among strains will prove to be mainly hereditary, then it will be also
      possible to select for either specific pH tolerance or tolerance at a wide range
      of pH. 

PMID- 24305797
TI  - Heterozygosity levels in a mammal: A determination derived from allele
      frequencies at loci controlling gross morphology.
AB  - Estimates of heterozygosity derived from electrophoretic data may seriously
      underestimate the true levels of genetic variability. An estimate derived from
      allele frequencies in Felis that relate to macroscopic morphological traits
      appears to be congruent with several theoretical predictions of heterozygosity
      levels. 

PMID- 24305798
TI  - The effect of positive assortative mating at one locus on a second linked locus :
      Part 1: the genotypic structure of the offspring generation.
AB  - A model for positive assortative mating based on genotype for one locus is
      employed to investigate the effect of this mating system on the genotypic
      structure of a second linked locus as well as on the joint genotypic structure of
      these two loci. It is shown that the second locus does not attain a precise
      positive assortative mating structure, but yet it shares a property that is
      characteristic of positive assortative mating, namely an increase in the
      frequency of homozygotes over that typically found in panmictic structures. Given
      any arbitrary genotypic structure for the parental population, the resulting
      offspring generation possesses a structure at the second locus that does not
      depend on the recombination frequency, while the joint structure of course does.
      In case assortative mating as well as linkage are not complete, there exists a
      unique joint equilibrium state for the two loci, which is characterized by
      complete stochastic independence between the two loci as well as by Hardy
      Weinberg proportions at the second locus. For the second locus alone, Hardy
      Weinberg equilibrium is realized if and only if gametic linkage equilibrium and
      an additionally specified condition are realized. 

PMID- 24305799
TI  - Effect of permethrin-impregnated underwear on body lice in sheltered homeless
      persons: a randomized controlled trial.
AB  - IMPORTANCE: The control of body lice in homeless persons remains a challenge.
      OBJECTIVE: To determine whether the use of long-lasting insecticide-treated
      underwear provides effective long-term protection against body lice in homeless
      persons. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo
      controlled trial was conducted in February and December 2011 in 2 homeless
      shelters (Madrague Ville and Forbin) in Marseille, France. Of the 125 homeless
      persons screened for eligibility, 73 body lice-infested homeless persons, 18
      years or older, were enrolled. INTERVENTIONS: Body lice-infested homeless persons
      were randomly assigned to receive 0.4% permethrin-impregnated underwear or an
      identical-appearing placebo for 45 days, in a 1:1 ratio, with a permuted block
      size of 10. Visits were scheduled at days 14 and 45. Data regarding the presence
      or absence of live body lice were collected. MAIN OUTCOMES AND MEASURES: The
      primary and secondary end points were the proportions of homeless persons free of
      body lice on days 14 and 45, respectively. Mutations associated with permethrin
      resistance in the body lice were also identified. RESULTS: Significantly more
      homeless persons receiving permethrin-impregnated underwear than homeless persons
      receiving the placebo were free of body lice on day 14 in the intent-to-treat
      population (28% vs 9%; P = .04), with a between-group difference of 18.4
      percentage points (95% CI, 1.4-35.4), and in the per-protocol population (34% vs
      11%; P = .03), with a between-group difference of 23.7 percentage points (95% CI,
      3.6-43.7). This difference was not sustained on day 45. At baseline, the
      prevalence of the permethrin-resistant haplotype was 51% in the permethrin group
      and 44% in the placebo group. On day 45, the permethrin-resistant haplotype was
      significantly more frequent in the permethrin group than in the placebo group
      (73% vs 45%, P < .001). CONCLUSION AND RELEVANCE: Permethrin-impregnated
      underwear is more efficient than placebo at eliminating body louse infestations
      by day 14; however, this difference was not sustained on day 45. The use of
      permethrin may have increased the resistance to permethrin in body lice and thus
      must be avoided. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01287663.

PMID- 24305800
TI  - Probing the anti-aging role of polydatin in Caenorhabditis elegans on a chip.
AB  - C. elegans is widely used as a model organism in the study of aging and
      evaluation of anti-aging drugs due to its unique characteristics. In this work,
      we set out to investigate polydatin, a natural resveratrol glycoside, and its
      role in extending lifespan, improving oxidative stress resistance, and the
      possible regulation mechanism involved in the Insulin/IGF-1 signaling (IIS)
      pathway for the first time by using a flexible microfluidic device. The effects
      of polydatin on the lifespan, oxidative stress resistance, mobility and the
      expression of aging-related proteins and genes were explored. Polydatin was found
      to significantly extend the mean lifespan of worms by up to 30.7% and 62.1% under
      normal and acute stress conditions respectively. It improved the expression of
      the inducible oxidative stress protein (GST-4) and corresponding stroke
      frequencies in the transgenic CL2166 strain. Moreover, it also increased SOD
      3::GFP expression in CF1553 worms and promoted DAF-16 nucleus translocation in
      TJ356 worms. The longevity-extending role of polydatin is partly attributed to
      its anti-oxidative activity and increased oxidative stress resistance by
      regulating the stress-resistance related proteins SOD-3, and daf-16 expression at
      protein and mRNA levels involved in the IIS pathway. The established microfluidic
      platform is capable of flexible operation with multiple functions, which not only
      supports the individual worm's long-term culture with sufficient nutrient
      exchange, but also facilitates mobility monitoring of the worm, immobilizing and
      imaging in a controllable and parallel manner. These interesting findings
      reported here highlight the significance of the natural compound polydatin in the
      study of aging-related diseases, and the utility of the microfluidic platform for
      applications in aging studies. 

PMID- 24305801
TI  - The rules of entrainment: are CA1 gamma oscillations externally imposed or
      locally governed?

PMID- 24305802
TI  - Contribution of postsynaptic molecules to AMPA receptor nanodomain organization.

PMID- 24305803
TI  - Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin
      releasing hormone release.
AB  - Release of gonadotropin releasing hormone (GnRH) from the medial basal
      hypothalamus (MBH)/median eminence region (S-ME) is essential for normal
      reproductive function. GnRH release is profoundly regulated by the negative and
      positive feedback effects of ovarian estradiol (E2). Here we report that
      neuroestradiol, released in the S-ME, also directly influences GnRH release in
      ovariectomized female monkeys, in which the ovarian source of E2 is removed. We
      found that (1) brief infusion of E2 benzoate (EB) to the S-ME rapidly stimulated
      release of GnRH and E2 in the S-ME of ovariectomized monkeys, (2) electrical
      stimulation of the MBH resulted in GnRH release as well as E2 release, and (3)
      direct infusion of an aromatase inhibitor to the S-ME suppressed spontaneous GnRH
      release as well as the EB-induced release of GnRH and E2. These findings reveal
      the importance of neuroestradiol as a neurotransmitter in regulation of GnRH
      release. How circulating ovarian E2 interacts with hypothalamic neuroestrogens in
      the control of GnRH release remains to be investigated. 

PMID- 24305804
TI  - The irrationality of categorical perception.
AB  - Perception is often categorical: the perceptual system selects one interpretation
      of a stimulus even when evidence in favor of other interpretations is
      appreciable. Such categorization is potentially in conflict with normative
      decision theory, which mandates that the utility of various courses of action
      should depend on the probabilities of all possible states of the world, not just
      that of the one perceived. If these probabilities are lost as a result of
      categorization, choice will be suboptimal. Here we test for such irrationality in
      a task that requires human observers to combine perceptual evidence with the
      uncertain consequences of action. Observers made rapid pointing movements to
      targets on a touch screen, with rewards determined by perceptual and motor
      uncertainty. Across both visual and auditory decision tasks, observers
      consistently placed too much weight on perceptual uncertainty relative to action
      uncertainty. We show that this suboptimality can be explained as a consequence of
      categorical perception. Our findings indicate that normative decision making may
      be fundamentally constrained by the architecture of the perceptual system. 

PMID- 24305805
TI  - Antagonistic functions of Dishevelleds regulate Frizzled3 endocytosis via
      filopodia tips in Wnt-mediated growth cone guidance.
AB  - How growth cones detect small concentration differences of guidance cues for
      correct steering remains a long-standing puzzle. Commissural axons engage planar
      cell polarity (PCP) signaling components to turn anteriorly in a Wnt gradient
      after midline crossing. We found here that Frizzled3, a Wnt receptor, undergoes
      endocytosis via filopodia tips. Wnt5a increases Frizzled3 endocytosis, which
      correlates with filopodia elongation. We discovered an unexpected antagonism
      between Dishevelleds, which may function as a signal amplification mechanism in
      filopodia where PCP signaling is activated: Dishevelled2 blocks Dishevelled1
      induced Frizzled3 hyperphosphorylation and membrane accumulation. A key component
      of apical-basal polarity (A-BP) signaling, aPKC, also inhibits Dishevelled1
      induced Frizzled3 hyperphosphorylation. Celsr3, another PCP component, is
      required in commissural neurons for anterior turning. Frizzled3
      hyperphosphorylation is increased in Celsr3 mutant mice, where PCP signaling is
      impaired, suggesting Frizzled3 hyperphosphorylation does correlate with loss of
      PCP signaling in vivo. Furthermore, we found that the small GTPase, Arf6, which
      is required for Frizzled3 endocytosis, is essential for Wnt-promoted outgrowth,
      highlighting the importance of Frizzled3 recycling in PCP signaling in growth
      cone guidance. In a Wnt5a gradient, more Frizzled3 endocytosis and activation of
      atypical protein kinase C was observed on the side of growth cones facing higher
      Wnt5a concentration, suggesting that spatially controlled Frizzled3 endocytosis
      is part of the key mechanism for growth cone steering. 

PMID- 24305807
TI  - Peripheral TGF-beta1 signaling is a critical event in bone cancer-induced
      hyperalgesia in rodents.
AB  - Pain is the most common symptom of bone cancer. TGF-beta, a major bone-derived
      growth factor, is largely released by osteoclast bone resorption during the
      progression of bone cancer and contributes to proliferation, angiogenesis,
      immunosuppression, invasion, and metastasis. Here, we further show that TGF-beta1
      is critical for bone cancer-induced pain sensitization. We found that, after the
      progression of bone cancer, TGF-beta1 was highly expressed in tumor-bearing bone,
      and the expression of its receptors, TGFbetaRI and TGFbetaRII, was significantly
      increased in the DRG in a rat model of bone cancer pain that is based on
      intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade
      of TGF-beta receptors by the TGFbetaRI antagonist SD-208 robustly suppressed bone
      cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral
      injection of TGF-beta1 directly induced thermal hyperalgesia in intact rats and
      wide-type mice, but not in Trpv1(-/-) mice. Whole-cell patch-clamp recordings
      from DRG neurons showed that transient receptor potential vanilloid (TRPV1)
      sensitivity was significantly enhanced on PTD 14. Extracellular application of
      TGF-beta1 significantly potentiated TRPV1 currents and increased [Ca(2+)]i in DRG
      neurons. Pharmacological studies revealed that the TGF-beta1 sensitization of
      TRPV1 and the induction of thermal hyperalgesia required the TGF-betaR-mediated
      Smad-independent PKCepsilon and TGF-beta activating kinase 1-p38 pathways. These
      findings suggest that TGF-beta1 signaling contributes to bone cancer pain via the
      upregulation and sensitization of TRPV1 in primary sensory neurons and that
      therapeutic targeting of TGF-beta1 may ameliorate the bone cancer pain in
      advanced cancer. 

PMID- 24305806
TI  - Pharmacologic inhibition of ROCK2 suppresses amyloid-beta production in an
      Alzheimer's disease mouse model.
AB  - Alzheimer's disease (AD) is the leading cause of dementia and has no cure.
      Genetic, cell biological, and biochemical studies suggest that reducing amyloid
      beta (Abeta) production may serve as a rational therapeutic avenue to delay or
      prevent AD progression. Inhibition of RhoA, a Rho GTPase family member, is
      proposed to curb Abeta production. However, a barrier to this hypothesis has been
      the limited understanding of how the principal downstream effectors of RhoA, Rho
      associated, coiled-coil containing protein kinase (ROCK) 1 and ROCK2, modulate
      Abeta generation. Here, we report that ROCK1 knockdown increased endogenous human
      Abeta production, whereas ROCK2 knockdown decreased Abeta levels. Inhibition of
      ROCK2 kinase activity, using an isoform-selective small molecule (SR3677),
      suppressed beta-site APP cleaving enzyme 1 (BACE1) enzymatic action and
      diminished production of Abeta in AD mouse brain. Immunofluorescence and confocal
      microscopy analyses revealed that SR3677 alters BACE1 endocytic distribution and
      promotes amyloid precursor protein (APP) traffic to lysosomes. Moreover, SR3677
      blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654
      was critical for APP processing to Abeta. These observations suggest that ROCK2
      inhibition reduces Abeta levels through independent mechanisms. Finally, ROCK2
      protein levels were increased in asymptomatic AD, mild cognitive impairment, and
      AD brains, demonstrating that ROCK2 levels change in the earliest stages of AD
      and remain elevated throughout disease progression. Collectively, these findings
      highlight ROCK2 as a mechanism-based therapeutic target to combat Abeta
      production in AD. 

PMID- 24305808
TI  - Synaptic plasticity and PDGF signaling defects underlie clinical progression in
      multiple sclerosis.
AB  - Neuroplasticity is essential to prevent clinical worsening despite continuing
      neuronal loss in several brain diseases, including multiple sclerosis (MS). The
      precise nature of the adaptation mechanisms taking place in MS brains, ensuring
      protection from disability appearance and accumulation, is however unknown. Here,
      we explored the hypothesis that long-term synaptic potentiation (LTP),
      potentially able to minimize the effects of neuronal loss by providing extra
      excitation of denervated neurons, is the most relevant form of adaptive
      plasticity in stable MS patients, and it is disrupted in progressing MS patients.
      We found that LTP, explored by means of transcranial magnetic theta burst
      stimulation over the primary motor cortex, was still possible, and even favored,
      in stable relapsing-remitting (RR-MS) patients, whereas it was absent in
      individuals with primary progressive MS (PP-MS). We also provided evidence that
      platelet-derived growth factor (PDGF) plays a substantial role in favoring both
      LTP and brain reserve in MS patients, as this molecule: (1) was reduced in the
      CSF of PP-MS patients, (2) enhanced LTP emergence in hippocampal mouse brain
      slices, (3) was associated with more pronounced LTP in RR-MS patients, and (4)
      was associated with the clinical compensation of new brain lesion formation in RR
      MS. Our results show that brain plasticity reserve, in the form of LTP, is
      crucial to contrast clinical deterioration in MS. Enhancing PDGF signaling might
      represent a valuable treatment option to maintain brain reserve and to attenuate
      the clinical consequences of neuronal damage in the progressive phases of MS and
      in other neurodegenerative disorders. 

PMID- 24305810
TI  - Distinct determinants of sparse activation during granule cell maturation.
AB  - Adult neurogenesis continually produces a small population of immature granule
      cells (GCs) within the dentate gyrus. The physiological properties of immature
      GCs distinguish them from the more numerous mature GCs and potentially enables
      distinct network functions. To test how the changing properties of developing GCs
      affect spiking behavior, we examined synaptic responses of mature and immature
      GCs in hippocampal slices from adult mice. Whereas synaptic inhibition restricted
      GC spiking at most stages of maturation, the relative influence of inhibition,
      excitatory synaptic drive, and intrinsic excitability shifted over the course of
      maturation. Mature GCs received profuse afferent innervation such that spiking
      was suppressed primarily by inhibition, whereas immature GC spiking was also
      limited by the strength of excitatory drive. Although the input resistance was a
      reliable indicator of maturation, it did not determine spiking probability at
      immature stages. Our results confirm the existence of a transient period during
      GC maturation when perforant path stimulation can generate a high probability of
      spiking, but also reveal that immature GC excitability is tempered by functional
      synaptic inhibition and reduced excitatory innervation, likely maintaining the
      sparse population activity observed in vivo. 

PMID- 24305809
TI  - Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine:
      implications for animal models of the motivational symptoms of depression.
AB  - Motivated behaviors are often characterized by a high degree of behavioral
      activation, and work output and organisms frequently make effort-related
      decisions based upon cost/benefit analyses. Moreover, people with major
      depression and other disorders often show effort-related motivational symptoms
      such as anergia, psychomotor retardation, and fatigue. It has been suggested that
      tasks measuring effort-related choice behavior could be used as animal models of
      the motivational symptoms of depression, and the present studies characterized
      the effort-related effects of the vesicular monoamine transport (VMAT) inhibitor
      tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, because
      of its selective inhibition of VMAT-2, it preferentially depletes dopamine (DA).
      Rats were assessed using a concurrent fixed-ratio 5/chow feeding choice task that
      is known to be sensitive to dopaminergic manipulations. Tetrabenazine shifted
      response choice in rats, producing a dose-related decrease in lever pressing and
      a concomitant increase in chow intake. However, it did not alter food intake or
      preference in parallel free-feeding choice studies. The effects of tetrabenazine
      on effort-related choice were reversed by the adenosine A2A antagonist MSX-3 and
      the antidepressant bupropion. A behaviorally active dose of tetrabenazine
      decreased extracellular DA in nucleus accumbens and increased expression of DARPP
      32 in accumbens medium spiny neurons in a pattern indicative of reduced
      transmission at both D1 and D2 DA receptors. These experiments demonstrate that
      tetrabenazine, which is used in animal models to produce depression-like effects,
      can alter effort-related choice behavior. These studies have implications for the
      development of animal models of the motivational symptoms of depression and
      related disorders. 

PMID- 24305811
TI  - Secretagogue stimulation of neurosecretory cells elicits filopodial extensions
      uncovering new functional release sites.
AB  - Regulated exocytosis in neurosecretory cells relies on the timely fusion of
      secretory granules (SGs) with the plasma membrane. Secretagogue stimulation leads
      to an enlargement of the cell footprint (surface area in contact with the
      coverslip), an effect previously attributed to exocytic fusion of SGs with the
      plasma membrane. Using total internal reflection fluorescence microscopy, we
      reveal the formation of filopodia-like structures in bovine chromaffin and PC12
      cells driving the footprint expansion, suggesting the involvement of cortical
      actin network remodeling in this process. Using exocytosis-incompetent PC12
      cells, we demonstrate that footprint enlargement is largely independent of SG
      fusion, suggesting that vesicular exocytic fusion plays a relatively minor role
      in filopodial expansion. The footprint periphery, including filopodia, undergoes
      extensive F-actin remodeling, an effect abolished by the actomyosin inhibitors
      cytochalasin D and blebbistatin. Imaging of both Lifeact-GFP and the SG marker
      protein neuropeptide Y-mCherry reveals that SGs actively translocate along newly
      forming actin tracks before undergoing fusion. Together, these data demonstrate
      that neurosecretory cells regulate the number of SGs undergoing exocytosis during
      sustained stimulation by controlling vesicular mobilization and translocation to
      the plasma membrane through actin remodeling. Such remodeling facilitates the de
      novo formation of fusion sites. 

PMID- 24305812
TI  - Integration over multiple timescales in primary auditory cortex.
AB  - Speech and other natural vocalizations are characterized by large modulations in
      their sound envelope. The timing of these modulations contains critical
      information for discrimination of important features, such as phonemes. We
      studied how depression of synaptic inputs, a mechanism frequently reported in
      cortex, can contribute to the encoding of envelope dynamics. Using a nonlinear
      stimulus-response model that accounted for synaptic depression, we predicted
      responses of neurons in ferret primary auditory cortex (A1) to stimuli with
      natural temporal modulations. The depression model consistently performed better
      than linear and second-order models previously used to characterize A1 neurons,
      and it produced more biologically plausible fits. To test how synaptic depression
      can contribute to temporal stimulus integration, we used nonparametric maximum a
      posteriori decoding to compare the ability of neurons showing and not showing
      depression to reconstruct the stimulus envelope. Neurons showing evidence for
      depression reconstructed stimuli over a longer range of latencies. These findings
      suggest that variation in depression across the cortical population supports a
      rich code for representing the temporal dynamics of natural sounds. 

PMID- 24305815
TI  - Diabetes augments in vivo microvascular blood flow dynamics after stroke.
AB  - Stroke usually affects people with underlying medical conditions. In particular,
      diabetics are significantly more likely to have a stroke and the prognosis for
      recovery is poor. Because diabetes is associated with degenerative changes in the
      vasculature of many organs, we sought to determine how hyperglycemia affects
      blood flow dynamics after an ischemic stroke. Longitudinal in vivo two-photon
      imaging was used to track microvessels before and after photothrombotic stroke in
      a diabetic mouse model. Chronic hyperglycemia exacerbated acute (3-7 d) ischemia
      induced increases in blood flow velocity, vessel lumen diameter, and red blood
      cell flux in peri-infarct regions. These changes in blood flow dynamics were most
      evident in superficial blood vessels within 500 MUm from the infarct, rather than
      deeper or more distant cortical regions. Long-term imaging of diabetic mice not
      subjected to stroke indicated that these acute stroke-related changes in vascular
      function could not be attributed to complications from hyperglycemia alone.
      Treating diabetic mice with insulin immediately after stroke resulted in less
      severe alterations in blood flow within the first 7 d of recovery, but had more
      variable results at later time points. Analysis of microvessel branching patterns
      revealed that stroke led to a pruning of microvessels in peri-infarct cortex,
      with very few instances of sprouting. These results indicate that chronic
      hyperglycemia significantly affects the vascular response to ischemic stroke and
      that insulin only partially mitigates these changes. The combination of these
      acute and chronic alterations in blood flow dynamics could underlie diabetes
      related deficits in cortical plasticity and stroke recovery. 

PMID- 24305813
TI  - Direction selectivity mediated by adaptation in the owl's inferior colliculus.
AB  - Motion direction is a crucial cue for predicting future states in natural scenes.
      In the auditory system, the mechanisms that confer direction selectivity to
      neurons are not well understood. Neither is it known whether sound motion is
      encoded independently of stationary sound location. Here we investigated these
      questions in neurons of the owl's external nucleus of the inferior colliculus,
      where auditory space is represented in a map. Using a high-density speaker array,
      we show that the preferred direction and the degree of direction selectivity can
      be predicted by response adaptation to sounds moving over asymmetric spatial
      receptive fields. At the population level, we found that preference for sounds
      moving toward frontal space increased with eccentricity in spatial tuning. This
      distribution was consistent with larger receptive-field asymmetry in neurons
      tuned to more peripheral auditory space. A model of suppression based on
      spatiotemporal summation predicted the observations. Thus, response adaptation
      and receptive-field shape can explain direction selectivity to acoustic motion
      and an orderly distribution of preferred direction. 

PMID- 24305816
TI  - Transcranial direct current stimulation (tDCS) of left parietal cortex
      facilitates gesture processing in healthy subjects.
AB  - Gesture processing deficits constitute a key symptom of apraxia, a disorder of
      motor cognition frequently observed after left-hemispheric stroke. The clinical
      relevance of apraxia stands in stark contrast to the paucity of therapeutic
      options available. Transcranial direct current stimulation (tDCS) is a promising
      tool for modulating disturbed network function after stroke. Here, we investigate
      the effect of parietal tDCS on gesture processing in healthy human subjects.
      Neuropsychological and imaging studies suggest that the imitation and matching of
      hand gestures involve the left inferior parietal lobe (IPL). Using
      neuronavigation based on cytoarchitectonically defined anatomical probability
      maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants
      (n = 26). Before and after tDCS, subjects performed a gesture matching task and a
      person discrimination task for control. Changes in error rates and reaction times
      were analyzed for the effects of anodal and cathodal tDCS (compared with sham
      tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS
      applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over
      IPL-areas PF and PG did not elucidate significant effects. Taking into account
      tDCS electrode size and the central position of area PFm within IPL, it can be
      assumed that the observed effect is rather the result of a combined stimulation
      of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data
      confirm the pivotal role of the left IPL in gesture processing. Furthermore,
      anatomically guided tDCS of the left IPL may constitute a promising approach to
      neurorehabilitation of apraxic patients with gesture processing deficits. 

PMID- 24305814
TI  - Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell
      output via S-nitrosylation.
AB  - Coding a wide range of light intensities in natural scenes poses a challenge for
      the retina: adaptation to bright light should not compromise sensitivity to dim
      light. Here we report a novel form of activity-dependent synaptic plasticity,
      specifically, a "weighted potentiation" that selectively increases output of Mb
      type bipolar cells in the goldfish retina in response to weak inputs but leaves
      the input-output ratio for strong stimuli unaffected. In retinal slice
      preparation, strong depolarization of bipolar terminals significantly lowered the
      threshold for calcium spike initiation, which originated from a shift in
      activation of voltage-gated calcium currents (ICa) to more negative potentials.
      The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling
      as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO
      dependent ICa modulation was cGMP independent but could be blocked by N
      ethylmaleimide (NEM), indicating that NO acted via an S-nitrosylation mechanism.
      Importantly, the NO action resulted in a weighted potentiation of Mb output in
      response to small (<=-30 mV) depolarizations. Coincidentally, light flashes with
      intensity >= 2.4 * 10(8) photons/cm(2)/s lowered the latency of scotopic (<= 2.4
      * 10(8) photons/cm(2)/s) light-evoked calcium spikes in Mb axon terminals in an
      NEM-sensitive manner, but light responses above cone threshold (>= 3.5 * 10(9)
      photons/cm(2)/s) were unaltered. Under bright scotopic/mesopic conditions, this
      novel form of Mb output potentiation selectively amplifies dim retinal inputs at
      Mb -> ganglion cell synapses. We propose that this process might counteract
      decreases in retinal sensitivity during light adaptation by preventing the loss
      of visual information carried by dim scotopic signals.

PMID- 24305818
TI  - Electrophysiological properties of rostral ventrolateral medulla presympathetic
      neurons modulated by the respiratory network in rats.
AB  - The respiratory pattern generator modulates the sympathetic outflow, the strength
      of which is enhanced by challenges produced by hypoxia. This coupling is due to
      the respiratory-modulated presympathetic neurons in the rostral ventrolateral
      medulla (RVLM), but the underlining electrophysiological mechanisms remain
      unclear. For a better understanding of the neural substrates responsible for
      generation of this respiratory-sympathetic coupling, we combined
      immunofluorescence, single cell qRT-pCR, and electrophysiological recordings of
      the RVLM presympathetic neurons in in situ preparations from normal rats and rats
      submitted to a metabolic challenge produced by chronic intermittent hypoxia
      (CIH). Our results show that the spinally projected cathecholaminergic C1 and non
      C1 respiratory-modulated RVLM presympathetic neurons constitute a heterogeneous
      neuronal population regarding the intrinsic electrophysiological properties,
      respiratory synaptic inputs, and expression of ionic currents, albeit all neurons
      presented persistent sodium current-dependent intrinsic pacemaker properties
      after synaptic blockade. A specific subpopulation of non-C1 respiratory-modulated
      RVLM presympathetic neurons presented enhanced excitatory synaptic inputs from
      the respiratory network after CIH. This phenomenon may contribute to the
      increased sympathetic activity observed in CIH rats. We conclude that the
      different respiratory-modulated RVLM presympathetic neurons contribute to the
      central generation of respiratory-sympathetic coupling as part of a complex
      neuronal network, which in response to the challenges produced by CIH contribute
      to respiratory-related increase in the sympathetic activity. 

PMID- 24305817
TI  - Simultaneous EEG-fMRI reveals temporal evolution of coupling between supramodal
      cortical attention networks and the brainstem.
AB  - Cortical and subcortical networks have been identified that are commonly
      associated with attention and task engagement, along with theories regarding
      their functional interaction. However, a link between these systems has not yet
      been demonstrated in healthy humans, primarily because of data acquisition and
      analysis limitations. We recorded simultaneous EEG-fMRI while subjects performed
      auditory and visual oddball tasks and used these data to investigate the BOLD
      correlates of single-trial EEG variability at latencies spanning the trial. We
      focused on variability along task-relevant dimensions in the EEG for identical
      stimuli and then combined auditory and visual data at the subject level to
      spatially and temporally localize brain regions involved in endogenous
      attentional modulations. Specifically, we found that anterior cingulate cortex
      (ACC) correlates strongly with both early and late EEG components, whereas
      brainstem, right middle frontal gyrus (rMFG), and right orbitofrontal cortex
      (rOFC) correlate significantly only with late components. By orthogonalizing with
      respect to event-related activity, we found that variability in insula and
      temporoparietal junction is reflected in reaction time variability, rOFC and
      brainstem correlate with residual EEG variability, and ACC and rMFG are
      significantly correlated with both. To investigate interactions between these
      correlates of temporally specific EEG variability, we performed dynamic causal
      modeling (DCM) on the fMRI data. We found strong evidence for reciprocal
      effective connections between the brainstem and cortical regions. Our results
      support the adaptive gain theory of locus ceruleus-norepinephrine (LC-NE)
      function and the proposed functional relationship between the LC-NE system, right
      hemisphere ventral attention network, and P300 EEG response. 

PMID- 24305819
TI  - Circadian variation in gastric vagal afferent mechanosensitivity.
AB  - Food intake is coordinated to cellular metabolism by clock gene expression with a
      master clock in the suprachiasmatic nucleus synchronized by light exposure.
      Gastric vagal afferents play a role in regulating food intake, but it is unknown
      whether they exhibit circadian variation in their mechanosensitivity. We aimed to
      determine whether gastric vagal afferents express clock genes and whether their
      response to mechanical stimuli oscillates throughout the light/dark cycle. Nodose
      ganglia were collected from 8-week-old female C57BL/6 mice every 3 h starting at
      lights off (1800 h) to quantify Bmal1, Per1, Per2, and Nr1d1 mRNA by qRT-PCR.
      Additionally in vitro single-fiber recordings of gastric vagal mechanoreceptors
      were taken at all time points. Per1, Per2, Bmal1, and Nr1d1 mRNA is expressed in
      the nodose ganglia and levels oscillated over a 24 h period. In mice fed ad
      libitum, gastric content was 3 times higher at 0000 h and 0300 h than 1200 h. The
      response of tension receptors to 3 g stretch was reduced by up to 70% at 2100 h,
      0000 h, and 0300 h compared with 1200 h. Gastric mucosal receptor response to
      stroking with a 50 mg von Frey hair was 3 times greater at 1200 h and 1500 h than
      the response at 0000 h. Similar findings were obtained in mice fasted for 6 h or
      maintained in darkness for 3 d before study. Therefore, these changes do not
      result from food intake or the light/dark cycle. Thus, gastric vagal
      mechanoreceptors display circadian rhythm, which may act to control food intake
      differentially at different times of the day. 

PMID- 24305820
TI  - Consecutive TMS-fMRI reveals an inverse relationship in BOLD signal between
      object and scene processing.
AB  - The human visual system is capable of recognizing an infinite number of scenes
      containing an abundance of rich visual information. There are several cortical
      regions associated with the representation of a scene, including those
      specialized for object processing (the lateral occipital area [LO]) and for the
      spatial layout of scenes (the parahippocampal place area). Although behavioral
      studies have demonstrated that these image categories (scenes and objects) exert
      an influence on each other such that scene context can facilitate object
      identification or that scene categorization can be impaired by the presence of a
      salient object, little is known about the apparent cortical interactions involved
      in building the conscious representation of a complete scene. It has been shown
      that transcranial magnetic stimulation (TMS) to the left LO disrupts object
      categorization but facilitates scene categorization. Here, we show that this
      effect is also reflected by changes in the BOLD signal such that TMS to the left
      LO decreases BOLD signal at the stimulation site (LO) while viewing objects and
      increases BOLD signal in the left PPA when viewing scenes. This suggests that
      these regions, although likely not on a strict hierarchy of bottom-up coding,
      share functional communication likely in the form of inhibitory connections. 

PMID- 24305821
TI  - Sodium channels contribute to degeneration of dorsal root ganglion neurites
      induced by mitochondrial dysfunction in an in vitro model of axonal injury.
AB  - Axonal degeneration occurs in multiple neurodegenerative disorders of the central
      and peripheral nervous system. Although the underlying molecular pathways leading
      to axonal degeneration are incompletely understood, accumulating evidence
      suggests contributions of impaired mitochondrial function, disrupted axonal
      transport, and/or dysfunctional intracellular Ca(2+)-homeostasis in the injurious
      cascade associated with axonal degeneration. Utilizing an in vitro model of
      axonal degeneration, we studied a subset of mouse peripheral sensory neurons in
      which neurites were exposed selectively to conditions associated with the
      pathogenesis of axonal neuropathies in vivo. Rotenone-induced mitochondrial
      dysfunction resulted in neurite degeneration accompanied by reduced ATP levels
      and increased ROS levels in neurites. Blockade of voltage-gated sodium channels
      with TTX and reverse (Ca(2+)-importing) mode of the sodium-calcium exchanger
      (NCX) with KB-R7943 partially protected rotenone-treated neurites from
      degeneration, suggesting a contribution of sodium channels and reverse NCX
      activity to the degeneration of neurites resulting from impaired mitochondrial
      function. Pharmacological inhibition of the Na(+)/K(+)-ATPase with ouabain
      induced neurite degeneration, which was attenuated by TTX and KB-R7943,
      supporting a contribution of sodium channels in axonal degenerative pathways
      accompanying impaired Na(+)/K(+)-ATPase activity. Conversely, oxidant stress
      (H2O2)-induced neurite degeneration was not attenuated by TTX. Our results
      demonstrate that both energetic and oxidative stress targeted selectively to
      neurites induces neurite degeneration and that blockade of sodium channels and of
      reverse NCX activity blockade partially protects neurites from injury due to
      energetic stress, but not from oxidative stress induced by H2O2. 

PMID- 24305822
TI  - FAIM-L is an IAP-binding protein that inhibits XIAP ubiquitinylation and protects
      from Fas-induced apoptosis.
AB  - The neuronal long isoform of Fas Apoptotic Inhibitory Molecule (FAIM-L) protects
      from death receptor (DR)-induced apoptosis, yet its mechanism of protection
      remains unknown. Here, we show that FAIM-L protects rat neuronal Type II cells
      from Fas-induced apoptosis. XIAP has previously emerged as a molecular
      discriminator that is upregulated in Type II and downregulated in Type I
      apoptotic signaling. We demonstrate that FAIM-L requires sustained endogenous
      levels of XIAP to protect Type II cells as well as murine cortical neurons from
      Fas-induced apoptosis. FAIM-L interacts with the BIR2 domain of XIAP through an
      IAP-binding motif, the mutation of which impairs the antiapoptotic function of
      FAIM-L. Finally, we report that FAIM-L inhibits XIAP auto-ubiquitinylation and
      maintains its stability, thus conferring protection from apoptosis. Our results
      bring new understanding of the regulation of endogenous XIAP by a DR antagonist,
      pointing out at FAIM-L as a promising therapeutic tool for protection from
      apoptosis in pathological situations where XIAP levels are decreased.